PMID- 17203389
TI  - Biological and structural characterization of crotoxin and new isoform of
      crotoxin B PLA(2) (F6a) from Crotalus durissus collilineatus snake venom.
AB  - A new crotoxin B isoform PLA(2) (F6a), from Crotalus durissus collilineatus was
      purified from by one step reverse phase HPLC chromatography using mu-Bondapack C
      18 column analytic. The new crotoxin B isoform PLA(2) (F6a), complex crotoxin,
      the catalytic subunit crotoxin B isoform PLA(2) (F6a) and two crotapotin isoforms
      (F3 and F4), were isolated from the venom of Crotalus durissus collilineatus. The
      crotapotins isoforms F3 and F4 had similar chemical properties, the two proteins
      different in their ability to inhibit of isoforms of PLA(2) (F6 and F6a). The
      molecular masses estimated by MALDI-TOF mass spectrometry were: crotoxin B:
      14,943.14 Da, crotapotin F3: 8,693.24 Da, and crotapotin F4: 9 314.56 Da. The new
      crotoxin B isoform PLA(2) (F6a) contained 122 amino acid residues and a pI of
      8.58. Its amino acid sequence presents high identity with those of other PLA(2)s,
      particularly in the calcium binding loop and active site helix 3. It also
      presents similarities in the C-terminal region with other myotoxic PLA(2)s. The
      new crotoxin B isoform PLA(2) (F6a) contained 122 amino acid residues, with a
      primary structure of HLLQFNKMIK FETRRNAIPP YAFYGCYCGW GGRGRPKDAT DRCCFVHDCC
      YGKLAKCNTK WDFYRYSLKS GYITCGKGTW CEEQICECDR VAAECLRRSL STYRYGYMIY PDSRCRGPSE TC.
      A neuromuscular blocking activity was induced by crotoxin and new crotoxin B
      isoform PLA(2) (F6a) in the isolated mouse phrenic nerve diaphragm and the
      biventer cervicis chick nerve-muscle preparation. Whole crotoxin was devoid of
      cytolytic activity upon myoblasts and myotubes in vitro, whereas new crotoxin B
      isoform PLA(2) (F6a) was clearly cytotoxic to these cells.

PMID- 17203390
TI  - Isolation and biochemical characterization of a galactoside binding lectin from
      Bauhinia variegata candida (BvcL) seeds.
AB  - A new lectin (BvcL) from seeds of a primitive Brazilian Caesalpinoideae, the
      Bauhinia variegata candida was purified and biochemical characterized. BvcL was
      isolated by gel filtration chromatography on Sephadex G75 and affinity
      chromatography on immobilized D: -lactose column. SDS-PAGE showed that BvcL under
      non-reducing condition presents two bands of 68 and 32 kDa and a single band of
      32 kDa in reducing condition. However, only one band was seen in native PAGE. The
      hemagglutination activity of BvcL was not specific for any human blood group
      trypsin-treated erythrocytes. Carbohydrate inhibition analysis indicated that
      BvcL is inhibited by lactose, galactose, galactosamine and other galactoside
      derivates. Amino acid analysis revealed a large content of Ser, Gly, Thr, Asp and
      Glu and low concentrations of Met, Cys and His. Intrinsic fluorescence of BvcL
      was not significantly affected by sugar binding galactose; and aromatic-region CD
      is unusually high for plant lectins. The N-terminal amino acid sequence of 17
      residues showed 90% sequential homology to galactose-specific legume lectins of
      the subfamily Caesalpinoideae.

PMID- 17203391
TI  - Synergistic action of recombinant alpha-amylase and glucoamylase on the
      hydrolysis of starch granules.
AB  - Barley alpha-amylase 1 mutant (AMY) and Lentinula edodes glucoamylase (GLA) were
      cloned and expressed in Saccharomyces cerevisiae. The purified recombinant AMY
      hydrolyzed corn and wheat starch granules, respectively, at rates 1.7 and 2.5
      times that of GLA under the same reaction conditions. AMY and GLA synergistically
      enhanced the rate of hydrolysis by approximately 3x for corn and wheat starch
      granules, compared to the sum of the individual activities. The exo-endo
      synergism did not change by varying the ratio of the two enzymes when the total
      concentration was kept constant. A yield of 4% conversion was obtained after 25
      min 37 degrees C incubation (1 unit total enzyme, 15 mg raw starch granules, pH
      5.3). The temperature stability of the enzyme mixtures was < or =50 degrees C,
      but the initial rate of hydrolysis continued to increase with higher
      temperatures. Ca(++) enhanced the stability of the free enzymes at 50 degrees C
      incubation. Inhibition was observed with the addition of 10 mM Fe(++) or Cu(++),
      while Mg(++ )and EDTA had lesser effect.

PMID- 17203392
TI  - W-motif exchange between beta-propeller proteins.
AB  - The similarity between the structural scaffold of PQQGDH and that of sialidase in
      the absence of any similarity in the primary structure, catalytic function and
      substrate recognition encouraged us to attempt a W-motif exchange between these
      enzymes. By substituting one W-motif in PQQGDH with one from sialidase, a
      chimeric PQQGDH was constructed, and its enzymatic properties were investigated.
      The overexpression of the chimeric enzyme resulted in the formation of an
      inclusion body. However, the refolding procedure resulted in a soluble chimeric
      enzyme with PQQGDH activity showing similar secondary-structure components as
      native PQQGDH. In contrast to native PQQGDH, the chimeric PQQGDH showed thermal
      instability and sensitivity to EDTA; this difference might have been due to the
      incomplete compatibility of the inserted W-motif. The potential of W-motif
      replacement was also discussed in view of the possible molecular
      evolution/engineering of beta-propeller structures.

PMID- 17203393
TI  - Thermal destabilization of stem bromelain by trehalose.
AB  - Trehalose, a naturally occurring osmolyte, is considered as a universal protein
      stabilizer. We investigated the effect of the disaccharides, trehalose and
      sucrose, on the thermal stability and conformation of bromelain. To our surprise,
      bromelain in the presence of 1 M trehalose/sucrose was destabilized under thermal
      stress. The average Tm values as determined by UV spectroscopy and CD
      spectropolarimetry decreased by 5 degrees and 7 degrees C for bromelain in 1 M
      sucrose or trehalose solutions, respectively. The enzyme was also found to
      inactivate faster at 60 degrees C in the presence of these osmolytes. The
      tertiary and secondary structure of bromelain undergoes small changes in the
      presence of sucrose/trehalose. Studies on the binding of these osmolytes with the
      native and the heat denatured enzyme revealed that sucrose/trehalose lead to
      preferential hydration of the denatured bromelain as compared to the native one,
      hence stabilizing more the denatured conformation. This is perhaps the first
      report on the destabilization of a protein by trehalose.

PMID- 17203394
TI  - A split enhanced green fluorescent protein-based reporter in yeast two-hybrid
      system.
AB  - We have developed a novel reporter system involving a yeast two-hybrid assay,
      which utilizes the reconstitution of the split EGFP reporter in order to
      characterize the relevant protein-protein interactions. To our knowledge, this
      study represents the first application of the split EGFP system as a read-out in
      a yeast two-hybrid assay. In comparison with the existing two-hybrid system, the
      bait and prey vectors were improved with regard to the reporter and the
      replication control element. As a result, the reconstituted EGFP has been
      observed to evidence a restored fluorescence upon protein-protein interactions in
      yeast, thereby allowing for the characterization of its interactor. The use of a
      split EGFP reporter has some salient advantages. Firstly, no substrates are
      required for the production of fluorescence. Secondly, low copy number plasmids
      may help to solve the protein toxicity problem, via the reduction of expression.
      Thirdly, this technique may prove useful in overcoming the autoactivation
      problem, due to the fact that the read-out of the yeast two-hybrid system is
      transcription-independent. Collectively, our results showed that the split EGFP
      reporter system might potentially be applied in yeast two-hybrid assays for the
      high-throughput screening of protein-protein interactions, with a simple and
      direct fluorescent read-out.

PMID- 17203395
TI  - Characterization of cold-shock protein A of Antarctic Streptomyces sp. AA8321.
AB  - Polar organisms should have mechanisms to survive the extremely cold environment.
      Four genes encoding cold-shock proteins, which are small, cold-induced bacterial
      proteins, have been cloned from the Antarctic bacterium Streptomyces sp. AA8321.
      Since the specific functions of any polar bacterial or Streptomyces cold-shock
      proteins have not yet been determined, we examined the role of cold-shock protein
      A from Streptomyces sp. AA8321 (CspA(St)). Gel filtration chromatography showed
      that purified CspA(St) exists as a homodimer under physiological conditions, and
      gel shift assays showed that it binds to single-stranded, but not double
      stranded, DNA. Overexpression of CspA(St) in Escherichia coli severely impaired
      the ability of the host cells to form colonies, and the cells developed an
      elongated morphology. Incorporation of a deoxynucleoside analogue, 5-bromo-2'
      deoxyuridine, into newly synthesized DNA was also drastically diminished in
      CspA(St)-overexpressing cells. These results suggest that CspA(St) play a role in
      inhibition of DNA replication during cold-adaptation.

PMID- 17203397
TI  - Convection enhanced delivery for treating brain tumors and selected neurological
      disorders: symposium review.
AB  - In 2003 the Cleveland Clinic Brain Tumor Institute sponsored a symposium to mark
      the progress being made in what was then a new approach to treating brain tumors 
      convection enhanced delivery (CED) [Vogelbaum MA (2005) J NeuroOncol 73(1):57
      69]. A second symposium was held in February, 2006, to review new accomplishments
      and identify promising avenues of research in this evolving but still novel
      therapy. Among the general subjects covered by a host of international experts in
      their respective fields were advances in CED technology, new clinical
      applications of the technology, advances in CED-related imaging procedures,
      reviews of current or proposed trials, new drugs and the status of projects
      moving from lab to clinical practice. Specific subjects included the design of
      new catheters, the development of mathematic models for planning, novel
      therapeutics for CED treatment of stroke, spinal cord degenerative disease and
      epilepsy, liposome-based agents administered via CED, ultra-sound driven CED,
      monitoring the in vivo effects of intratumoral paclitaxel and other topics. Each
      speaker's presentation has been abstracted along with relevant references.

PMID- 17203396
TI  - Biochemical, pharmacological and structural characterization of two PLA2 isoforms
      Cdr-12 and Cdr-13 from Crotalus durissus ruruima snake venom.
AB  - Cdr-12 and Cdr-13 isoforms of PLA2, a D49 protein, were purified from Crotalus
      durissus ruruima venom after one chromatographic step, reverse phase HPLC on
      micro-Bondapack C-18. The molecular mass by SDS-PAGE of Cdr-12 and Cdr-13
      isoforms of PLA2 was 14333.49 Da and 14296.42 Da, respectively and confirmed by
      MALDI-TOF mass spectrometry. The amino acid composition showed that both isoforms
      Cdr-12 and Cdr-13 have a high content of Lys, Tyr, Gly, Arg, and 14 half-Cys
      residues, typical of a basic PLA2. The isoforms Cdr-12 and Cdr-13 had a sequence
      of amino acids of 122 amino acid residues, being Cdr-12: SLLQFNKMIK FETRKNAIPF
      YAFYGCYCGW GGQGRPKDAT DRCCIVHDCC YGKLAKCNTK WDFYRYSLRS GYFQCGKGTW CEQQICECDR
      VAAECLRRSL STYRYGYMIY PDSRCREPSE TC and pI value 8.37 and Cdr-13: SLVQFEKMIK
      EETGKNAVPF YAFYGCYCGW GGRGRPKDAT DRCCIVHDCC YEKLVKCNTK WDFYRYSLRS GYFQCGKGTW
      CEQQICECDR VAAECLRRSL STYRYGKMIY PDSRCREPSE TC with a pI value of 8.13 This
      sequence shows high identity values when compared to other D49 PLA2s isolated
      from venoms of crotalics snakes. Skeletal muscle preparations from the young
      chicken have been previously used in order to study the effects of toxins on
      neuromuscular transmission, providing an important opportunity to study the
      differentiated behavior of a toxin before more than one model, because it shows
      differences in its sensibilities. In mice, the PLA2 isoforms Cdr-12 and Cdr-13
      induced myonecrosis and edema, upon intramuscular or subcutaneous injections,
      respectively. In vitro, Cdr-12 and Cdr-13 isoforms of PLA2, caused a potent
      blockade of neuromuscular transmission in young chicken biventer cervicis
      preparation and produced cytotoxicity in murine C2C12 skeletal muscle myotubes
      and lack cytolytic activity upon myoblasts in vitro. Thus, the combined
      structural and functional information obtained identify Cdr-12 and Cdr-13
      isoforms as members of the PLA2 family, which presents the typical bioactivities
      described for such proteins.

PMID- 17203398
TI  - Primary peripheral primitive neuroectodermal tumors of the spinal cord: report of
      two cases and review of the literature.
AB  - Primary intraspinal peripheral primitive neuroectodermal tumors (pPNETs) are
      extremely rare tumors with only seven reported cases in the literature. The
      histopathologic diagnosis of this tumor is complex and has led to a variety of
      treatment approaches. The distinction between central and peripheral type primary
      spinal cord PNETs has not always been made in the literature, leading to a
      paucity of data in this disease. We present here two young patients with primary
      intraspinal pPNET, their treatment and outcome. The first patient, a 27 year old
      male, presented with an intradural mass extending from L2 through L5, after
      multiple relapses, he is currently alive with disease after 72 months, the
      longest survival yet reported. The second patient, a 16 year old female,
      presented with an intradural mass at the cauda equina from L2 through L5, and is
      currently alive with responsive disease at 5 months after initial diagnosis.
      Here, we discuss the clinical course, the pathology and treatment for this
      disease and review the literature.

PMID- 17203399
TI  - Optimal planar flow network designs for tissue engineered constructs with built
      in vasculature.
AB  - Convective delivery of nutrients is important to enhance mass transport within
      tissue engineered (TE) products. Depending on the target tissue, an ideal TE
      product will have an integrated microvasculature that will eliminate mass
      transport limitations that can occur during product growth in vitro and
      integration in vivo. A synthetic approach to develop microvasculature involves
      development of network designs with efficient mass transfer characteristics. In
      this paper, utilizing a planar bifurcating network as a basis, we develop an
      approach to design optimal flow networks that have maximum mass transport
      efficiency for a given pressure drop. We formulated the optimization problem for
      a TE skin product, incorporating two types of duct flow, rectangular and square,
      and solved using a generalized reduced gradient algorithm. Under the conditions
      of this study, we found that rectangular ducts have superior mass transport
      characteristics than square ducts. Microvascular area per volume values obtained
      in this work are significantly greater than those reported in the literature. We
      discuss the effect of network variables such as porosity and generations on the
      optimal designs. This research forms the engineering basis for the rational
      development of TE products with built-in microvasculature and will pave the way
      to design complex flow networks with optimal mass transfer characteristics.

PMID- 17203400
TI  - 2D:4D and sexually dimorphic facial characteristics.
AB  - The second-to-fourth-digit ratio (2D:4D) may be related to prenatal testosterone
      and estrogen levels and pubertal face growth. Several studies have recently
      provided evidence that 2D:4D is associated with other-rated facial masculinity
      and dominance, but not with facialmetric measures of masculinity. We found that
      localized face shape differences, shown here to be sexually dimorphic and related
      to ratings of dominance, were associated with direct and indirect measurements of
      2D:4D. In this study we examined various localized features of the face, showing
      nose width, jaw angle, and lip height to be sexually dimorphic. We then had faces
      rated for dominance and saw that the most dimorphic characteristics were those
      most associated with rated dominance, with typically masculine characteristics
      tending to be associated with high ratings of dominance. Finally, 2D:4D
      measurements were made using three different techniques. High (feminine) values
      of 2D:4D were associated with feminine facial characteristics in women, but not
      in men. It was concluded that certain aspects of facial development are governed
      by factors that are established prenatally. These aspects may be associated with
      perceptions of the self by others that are important in the social environment,
      particularly in terms of intra-sexual competition and mate acquisition.

PMID- 17203401
TI  - Evidence for the involvement of p38 MAP kinase in the action of the vascular
      disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA).
AB  - AIMS: DMXAA (AS1404), a small-molecule vascular disrupting agent that has now
      completed Phase II clinical trial, induces endothelial cell apoptosis, increased
      vascular permeability and decreased tumour blood flow in vivo. Its action is
      incompletely understood and we wished to develop an in vitro system to study its
      effects. METHODS: Human tumour cell lines developed from aggressive tumours were
      grown on Matrigel to simulate a tumour microenvironment. Cells were analysed by
      light microscopy and by gene expression profiling. RESULTS: Several cell lines
      formed networks when grown on Matrigel and the NZM7 melanoma cell line was chosen
      for further study. Addition of DMXAA at a clinically achievable concentration (30
      microg/mL) prevented network formation, but co-addition of SB203580 (10 microM),
      a selective inhibitor of p38 MAP kinase, reversed the effect of DMXAA and
      restored network formation. Analysis of expression genes for endothelial and
      related functions showed that cells growing on Matrigel expressed a pattern
      similar to that of NZM7 cells growing as xenografts in vivo but different from
      that of cells grown on standard tissue culture plates. Addition of DMXAA resulted
      in the inhibition of expression of several genes including the transcriptional
      activator Ets1 and matrix metalloproteinase-2 (MMP2), but co-addition of SB203580
      did not reverse these effects of DMXAA on gene expression. CONCLUSION: The
      results suggest that p38 MAP kinase plays an important role in the action of
      DMXAA and that growth of tumour cells on Matrigel provides a promising model for
      further studies on the action of this drug.

PMID- 17203402
TI  - Stability of complex spike timing-dependent plasticity in cerebellar learning.
AB  - Dynamics of spike-timing dependent synaptic plasticity are analyzed for
      excitatory and inhibitory synapses onto cerebellar Purkinje cells. The purpose of
      this study is to place theoretical constraints on candidate synaptic learning
      rules that determine the changes in synaptic efficacy due to pairing complex
      spikes with presynaptic spikes in parallel fibers and inhibitory interneurons.
      Constraints are derived for the timing between complex spikes and presynaptic
      spikes, constraints that result from the stability of the learning dynamics of
      the learning rule. Potential instabilities in the parallel fiber synaptic
      learning rule are found to be stabilized by synaptic plasticity at inhibitory
      synapses if the inhibitory learning rules are stable, and conditions for
      stability of inhibitory plasticity are given. Combining excitatory with
      inhibitory plasticity provides a mechanism for minimizing the overall synaptic
      input. Stable learning rules are shown to be able to sculpt simple-spike patterns
      by regulating the excitability of neurons in the inferior olive that give rise to
      climbing fibers.

PMID- 17203403
TI  - Enhancement of intracellular delivery of CdTe quantum dots (QDs) to living cells
      by Tat conjugation.
AB  - Quantum dots (QDs), as novel fluorescence probes, have shown a great potential
      for bio-molecular labeling and cellular imaging. To stain cellular targets, the
      sufficient intracellular delivery of QDs is required. In this work the tat, a
      typical membrane-permeable carrier peptide, was conjugated with thiol-capped CdTe
      QDs to form CdTe Tat-QDs, and the intracellular deliveries of CdTe QDs or CdTe
      Tat-QDs were compared in human hepatocellular carcinoma (QGY) cells and human
      breast cancer (MCF7) cells in vitro by means of confocal laser scanning
      microscopy. Added into the cell dishes, both QDs and Tat-QDs adhered to the outer
      leaflet of the plasma membrane of cells within a few minutes, but the binding
      amount of Tat-QDs was obviously higher than that of QDs. Then both QDs and Tat
      QDs can penetrate into cells, and their cellular contents increased with
      incubation time but both saturated after 3 hours incubation. However the cellular
      levels of Tat-QDs were higher than those of QDs, with the ratio of 2.1 (+/-0.3)
      times in QGY cells and 1.5 (+/-0.2) times in MCF7 cells, demonstrating the
      enhancing effect of Tat conjugation on the intracellular delivery of QDs.

PMID- 17203404
TI  - Effects of irradiation on the postnatal development of the brain in a genetic
      mouse model of globoid cell leukodystrophy.
AB  - Irradiation is one way to condition Twitcher mice--a natural model of globoid
      cell leukodystrophy (GLD)--prior to receive bone marrow transplantation (BMT).
      BMT showed to delay but not to completely prevent GLD disease in treated mutants.
      The reasons why BMT is not completely preventive in Twitchers are unclear but we
      speculate that irradiation might contribute to worsen the neurological
      impairments generated by the disease by altering postnatal neurogenesis. To test
      this hypothesis, we examined proliferation, migration and differentiation of
      neural precursors in neurogenic areas of the Twitcher brain after exposure of 5
      day-old mutant pups to 620 rad, a non-lethal dose that leads to 80-90% of bone
      marrow engraftment in classic BMT. Twitchers showed to be sensitive to
      irradiation, leading to a severe retardation of body growth of irradiated
      mutants. Irradiated Twitchers had reduced proliferation of neural precursors and
      increased astrogliosis and microgliosis, with reduced numbers of migratory
      neuroblasts and significantly less brain myelination. These effects were
      accompanied by caspase-3 activation and appeared largely irreversible in the
      lifespan of the Twitcher. Our work confirms that exposure of the neonatal brain
      to irradiation conditions such as those performed prior to BMT, can lead to long
      lasting alterations of postnatal neurogenesis and myelination, which might
      contribute to worsen the progression of disease in these myelin mutants and to
      reduce the success of BMT.

PMID- 17203406
TI  - Genetic diversity in five Iranian native chicken populations estimated by
      microsatellite markers.
AB  - Iranian chicken genetic resources are characterized by a long history and a vast
      diversity. This study represents the first results from the selection and
      evaluation of five polymorphic microsatellite markers for the genetic assessment
      of five native chicken populations located in the northwestern (West Azerbaijan),
      northern (Mazandaran), central (Isfahan, Yazd), and southern (Fars) provinces of
      Iran. The number of alleles ranged from three to six per microsatellite locus.
      All populations were characterized by a high degree of genetic diversity, with
      the lowest heterozygosity found in the Isfahan population (62%) and the greatest
      in the populations from West Azerbaijan and Mazandaran (79%). The largest Nei's
      unbiased genetic distance was found between the Isfahan and Fars populations
      (0.696) and the smallest between the Mazandaran and Yazd populations (0.097). The
      Isfahan population was found to be the most genetically distant among all
      populations studied. These results serve as an initial step in the plan for
      genetic characterization and conservation of Iranian native chickens.

PMID- 17203407
TI  - A naturally occurring variant of porcine Mx1 associated with increased
      susceptibility to influenza virus in vitro.
AB  - Mx1 has been implicated in resistance to the influenza virus. We have now
      identified four alleles of the Mxl gene in domesticated breeds of pigs. Two of
      the alleles encode deletion variants (a 3-bp deletion in exon 13 and an 11-bp
      deletion in exon 14), which might be expected to interfere with Mx activity. The
      porcine Mxl genes corresponding to wild type, the 3-bp deletion mutant, and the
      11-bp deletion mutant were cloned and expressed in NIH3T3 cells, and the
      antiviral activity for influenza virus was assayed. Virus yield was observed to
      be 10-100-fold greater with the 11-bp deletion allele than that for wild type and
      the 3-bp deletion alleles. The results suggest that the 11-bp deletion type is
      lacking antiviral activity able to contribute to the interference of influenza
      virus replication.

PMID- 17203408
TI  - Special issue. George Albee tribute.

PMID- 17203405
TI  - Environmental factors in the development of Type 1 diabetes.
AB  - Environmental factors appear to play an important role in the pathogenesis of
      childhood-onset type 1 diabetes (T1D). The most important factors are thought to
      be infectious, dietary, perinatal, and psychosocial. Enteroviruses (especially
      Coxsackie B virus), breastfeeding, the early presence or lack of certain foods,
      birth weight, childhood over-nutrition, maternal islet autoimmunity, and negative
      stress events have been shown to be related to the prevalence of T1D. However,
      clear conclusions to date are limited because most studies lacked power to detect
      exposure/disease associations, were not prospective or long-term, did not start
      in infancy, had imprecise or infrequent exposure estimates, had confounding
      exposures, and failed to account for genetic susceptibility. In addition to the
      identification of specific antigenic triggers, several more general hypotheses,
      including the accelerator and hygiene hypotheses, are testable approaches worth
      pursuing.

PMID- 17203409
TI  - Viva George Albee!

PMID- 17203411
TI  - Incarceration and recidivism among sexual offenders.
AB  - The relationship between incarceration and recidivism was investigated in a
      sample of 627 adult male sexual offenders. Incarceration for the index offense
      was unrelated to sexual or violent recidivism. This was the case whether
      incarceration was examined as a dichotomous variable (incarceration vs. community
      sentence) or as a continuous variable (length of incarceration). Risk for sexual
      recidivism was assessed with a modified version of the Rapid Risk Assessment for
      Sexual Offense Recidivism. There was no evidence that the relationship between
      incarceration and recidivism was confounded or moderated by risk or that length
      of incarceration and recidivism were non-linearly associated. Sentencing sexual
      offenders to terms of incarceration appears to have little, if any, impact on
      sexual and violent recidivism following release.

PMID- 17203412
TI  - Violence and mental illness: a new analytic approach.
AB  - Empirical studies of violence and mental illness have used many different
      methods. Current state-of-the-art methods gather information from both subject
      and collateral interviews as well as official records. Typically these sources
      are treated as additive. Any report of a violent incident from any source is
      treated as true and all reported incidents are added to generate estimates of
      frequency. This paper presents a new statistical technique that uses the level of
      agreement between the sources of data to adjust those estimates. The evidence
      suggests that, although the additive technique for using multiple sources
      correctly estimates how many people are involved, it substantially underestimates
      the number of incidents. The new technique substantially reduces both false
      negatives and false positives.

PMID- 17203413
TI  - Shear bond strengths of glass-ionomer cements to sound and to prepared carious
      dentine.
AB  - The aim of this study was determine whether bonding of glass-ionomer cements to
      non-carious dentine differed from that to carious dentine. Five commercial
      cements were used, namely Fuji IX GP, Fuji IX capsulated, Fuji IX Fast capsulated
      (all GC, Japan), Ketac-Molar and Ketac-Molar Aplicap (both 3M-ESPE, Germany).
      Following conditioning of the substrate with 10% poly (acrylic acid) for 10 s,
      sets of 10 samples of the cements were bonded to prepared teeth that had been
      removed for orthodontic reasons. The teeth used had either sound dentine or
      sclerotic dentine. Shear bond strengths were determined following 24 h storage.
      For the auto-mixed cements, shear bond strength to sound dentine was found not to
      differ statistically from shear bond strength to sclerotic dentine whereas for
      hand-mixed cements, shear bond to sound dentine was found to be higher than to
      carious dentine (to at least p < 0.05). This shows that the chemical effects
      arising from interactions of glass-ionomer cements with the mineral phase of the
      tooth are the most important in developing strong bonds, at least in the shorter
      term.

PMID- 17203414
TI  - Methotrexate-added acrylic cement: biological and physical properties.
AB  - BACKGROUND: Previous reports have demonstrated the suitability of adding
      different chemotherapeutic drugs to acrylic cement for the treatment of bone
      metastases. The best results so far have been obtained with methotrexate (MTX)
      for which diffusion from the implanted cement has been demonstrated both in vitro
      and in vivo. In this study the suitability of adding MTX to acrylic cement as
      local adjuvant chemotherapy was investigated. METHODS: Using an in vitro model of
      human breast cancer cells we demonstrated that the drug is eluted in an active
      form able to exert a cytotoxic effect over a long period of time. The use of
      different concentrations of drug on the kinetic of elution and on the mechanical
      properties of cement was also evaluated. RESULTS: The results obtained suggest
      that the release of MTX is higher at the beginning and progressively decreases
      over time being affected by the concentration of drug used. Our results also
      demonstrated that the addition and the subsequent elution of MTX does not alter
      the compressive properties of the cement. CONCLUSION: These findings confirm the
      suitability of MTX-supplemented cement and support its use as an effective aid
      for the management of bone metastases requiring surgical curettage and acrylic
      cement implantation for structural support.

PMID- 17203415
TI  - Gender differences in global cardiovascular risk factors of obstructive sleep
      apnea patients.
AB  - The morbidity and mortality of obstructive sleep apnea (OSA) are related
      principally to its cardiovascular complications. Metabolic syndrome (MBS) is
      recognized as raising the risk of cardiovascular disease. In this study, we
      analysied the diagnostic value of MBS to predict the diagnosis of severe OSA.
      Eight-seven subjects (54 males and 33 females) without any cardiac or pulmonary
      disease referred for evaluation of OSA, had overnight polysomnography. MBS were
      diagnosed according to NCEP criteria. According to apnea-hypopnea index (AHI),
      subjects were divided into two groups: severe OSA (AHI>or=30, 26 males, 15
      females) and non-severe OSA (AHI<30, 28 males, 18 females). Ages were similar in
      both OSA groups for both genders. In the severe OSA group, number of patients
      with MBS was especially higher (in females n=13, 86.6%; in males n=19, 73%) than
      non-severe OSA (in females 6, 33%, in males 9, 32%). The mean values of the five
      diagnostic criteria of MBS were significantly higher in severe OSA than non
      severe groups in both genders. Analysis of diagnostic value (criteria>or=3) of
      MBS for predicting the diagnosis of severe OSA in males and females revealed the
      sensitivity 73% and 86.6%, the specificity 67.8% and 94.4%, positive predictive
      value 67.9% and 86.7%, negative predictive value 73% and 85.7% respectively.
      Especially in female patients referred to the sleep clinics, evaluation of MBS
      criteria may play an important role in predicting severe OSA with high
      sensitivity and negative predictivity. Furthermore, the presence of MBS in OSA
      patients might increase cardiovascular complications.

PMID- 17203416
TI  - [The prevalence of sleep related disorders among the drivers and it's relation
      with traffic accidents].
AB  - Studies consistently show that patients with sleep related diseases (SRD) have
      higher accident rates. Polysomnography (PSG) is the gold standard for the
      diagnosis of SRD. Sleep habits questionnaires are also useful tool for research
      of the prevalence of SRD on large populations. The aim of this study is to
      investigate the prevalence of SRD and SRD related traffic accidents on the whole
      population of professional drivers in Sivas city. A questionnaire that includes
      questions about drivers' background such as how long they have been driving, if
      they had any accidents, and if they drive just in Sivas city or inter state. This
      questionnaire composed of 50 questions about SRD and was asked to drivers answer
      them face to face. Three hundred forty male drivers participated for this study.
      Their mean age was 39.5+/-9.3 (21-68) years. The mean driving duration was 13.3+/
      7.9 years. The percentage of drivers who drove in Sivas was 52.1% and 47.9% of
      the drivers drove inter state. The percentage of drivers who had at least one
      accident was 36.3%. The prevalence of habitual snoring, insomnia, sleep apnea,
      nocturnal myoklonus were 41.2%, 39.1%, 32.9%, and 33.6% respectively. The traffic
      accident Odds ratio was 1.619 for drivers with habitual snoring (95% CI, 1.034 to
      2.536, p=0.02). In conclusion, this study found out that drivers with habituel
      snoring seems to have tendency (approximately 2-folds) of involving in traffic
      accidents than drivers who do not have habituel snoring. Polysomnography of
      candidate drivers with sleep disordered symptoms has to be logical before giving
      to driving license.

PMID- 17203417
TI  - Prevalence of asthma and respiratory symptoms by age, gender and smoking
      behaviour in Samsun, North Anatolia Turkey.
AB  - Asthma is a major health problem worldwide. This is the first study determining
      the prevalence of asthma among adults in Samsun which is situated in the centre
      of the Black Sea region of Turkey. The aim of our study was to assess the
      prevalence of asthma and asthmatic symptoms, and the relationships of these with
      age, gender and smoking behaviour in this region. A questionnaire interview
      adapted from the European Respiratory Community Health Survey (ERCHS) was
      performed by health centre officers with selected people between November
      December, 2002. The study population included a total of 1.916 [810 men (42.3%)
      and 1.106 women (57.7%)] inhabitants of Samsun city center, aged 15 years of age
      or above. The mean age was 37.8 years+/-15.5, the prevalence of asthma was 2.7%,
      receiving asthma medicine was 2.2%, the prevalence of wheezing in the last 12
      months was 15.5% and shortness of breath with wheezing was 11.6%. The frequency
      of symptoms was higher among the elderly population when compared to other groups
      (p<0.0001). Asthma diagnosis by a physician was more frequent among women
      (chi2=5.16, p<0.05). Morning cough, day time cough, chronic cough, phlegmy cough
      and waking up with cough symptoms were more frequent among the smokers (p<0.001).
      Asthma diagnosis and asthma treatment are at a very low level compared to
      reported asthma related symptoms.

PMID- 17203418
TI  - [The role of serum neopterin level in the evaluation of activation and response
      to treatment in the patients with pulmonary tuberculosis].
AB  - Neopterin is an important parameter showing cell mediated immunity activation. In
      this study we aimed to determine whether serum neopterin level could be used as a
      marker in the evaluation of tuberculosis activation and response to treatment.
      The study comprised 40 new case smear positive pulmonary tuberculosis patients
      and 40 healthy control. Serum neopterin levels were measured both before the
      treatment and 2nd month of the treatment in the patient group. The association
      between serum neopterin level and clinical, radiological and bacteriological
      parameters were also investigated. In patients with pulmonary tuberculosis the
      mean levels of serum neopterin were 35.1+/-13.4 nmol/L before the treatment and
      21.2+/-10.4 nmol/L in the 2nd month of the treatment. In the control group, serum
      neopterin level was 19+/-10.4 nmol/L. The serum neopterin levels of the patients
      were significantly higher than the control group (p=0.001). Also, there was
      significant difference between serum neopterin levels before the treatment and
      the 2nd month of the treatment (p=0.000). Serum neopterin level was higher in the
      group with extensive disease than the cases with limited disease (p=0.02). In
      conclusion, we think that serum neopterin level might be used as a reliable
      immunological marker in the evaluation of tuberculosis activation and response to
      treatment.

PMID- 17203419
TI  - [Tuberculosis screening results made at primary schools in Cizre].
AB  - Tuberculosis (Tbc) gained importance as a public health problem in the recent
      years. The course of the disease is more severe in childhood. Tbc screening was
      made by The Tuberculosis Control 11th Group Presidency on the primary school
      students in Cizre, in November 2005. A total of 2242 children have been taken to
      this study. Of the children, 1130 (50.4%) were boys and 1112 (49.6%) were girls.
      The mean age of the children was 6.9+/-0.8 (range, 4-14) years. Concerning
      Bacillus Calmette-Guerin (BCG) vaccine scar, 1676 (74.7%) children had no scar,
      536 children (23.9%) had single scar, and 32 children (1.4%) had double scar. The
      mean diameter of the tuberculin skin test (TST) was 2.1+/-2.7 mm. Regarding
      sexuality and TST mean diameter, statistically significant relation was not
      detected between girls and boys (p=0.3). The mean diameter of TST were 1.5+/-1.4
      mm, 3.5+/-4.0 mm and 11.2+/-3.3 mm in the children with no BCG scar, in those
      with single BCG scar, and in those with double BCG scar, respectively. Of the TST
      results of all children, 2065 (92.1%) were negative, 101 (4.5%) were attributed
      to BCG, and 76 (3.4%) were positive, respectively. The rate of positiveness of
      TST was 1.2% in the children with no BCG scar, 8.9% in the children with single
      BCG scar, and 50% in the children with double BCG scar, respectively. A
      statistically significant correlation between the increase in the BCG scar number
      and the increase in the TST mean diameter was detected (p<0.05). Of the children
      who were likely to have Tbc, 139 (6.2%) were advised to apply at the dispensary.
      Single BCG vaccination was inadequate in the children. We suggest encouraging the
      families about postpartal single BCG vaccination. Furthermore, school screenings
      should be paid greater attention.

PMID- 17203420
TI  - [The results of patients follow up at Gaziantep Number II Dispensary of
      Tuberculosis Control in the year 2004].
AB  - In this study, the aim was to investigate the performance of number-II Dispensary
      of Tuberculous Control (DTC) in Gaziantep in 2004. The patients diagnosed to have
      tuberculosis between 2004 January 1st and 2004 December 31st were included. The
      patients registries were evaluated retrospectively. The mean age of the patients
      was 28.92+/-14.43 years (ranged between 1-68), 70.5% of the cases were male, and
      72.5% of the cases were between 15-44 years old. Forty-two (82.3%) of the cases
      had the diagnosis of lung tuberculosis. 47% of them did not have any health
      insurance. The symptoms detected in the patients were cough, night sweats, sputum
      and hemoptysis respectively. There was no symptom registry in ten patients
      (19.6%). Sputum analysis to detect acid-fast bacilli (AFB) was done in 18
      patients (19.6%). AFB was perfomed in 3.9% of the patients following two-months
      of therapy, and in 1.9% of the patients at the end of the therapy. Diagnostic
      tuberculous culture was performed in only one patient (1.9%). There was no
      tuberculous culture performed neither at the second month nor at the end of the
      therapy course. AFB was found to be positive in direct or concentrated sputum
      samples in eight (44.4%) of the patients. All the patients were evaluated with
      radiographies. The eritrocyte sedimentation rate was measured in 33.3%, 9.8%, and
      15.6% of the patients before the therapy, at the end of the two months of
      therapy, and at the end of the therapy, respectively. The diagnosis was
      established with radiology clinical findings in 34 patients (66.6%). Directly
      observed therapy was performed in one patient (1.9%). The cure rate among smear
      positive patients was 12.5%, and the 100% of the patients were completed the
      therapy. There exists many problems with tuberculosis "warfare" and we believe
      the solution lies in DOTS.

PMID- 17203421
TI  - Clinical and social characteristics of the patients with tuberculosis in Eastern
      Anatolia.
AB  - Tuberculosis (TB) is an important public-health problem. The risk factors for TB
      are well-known. However, there may be some regional differences. In this study,
      we aimed to investigate the demographic characteristics and regional risk factors
      for TB and to discuss possible explanations for the difference. The study
      included totally 253 hospitalized patients (145 male and 108 female, with an
      average age 38+/-18) with TB (117 pulmonary and 136 extrapulmonary) between 1997
      and 2004. Their demographic and clinical characteristics were reviewed. TB
      frequency was higher among the non-working females in urban area (38.3%). TB was
      also common in farmers which are male (19.8%). TB frequency was higher in the
      school persons including students, the teachers and the school officials (14.6%)
      and in the building workers compared with the other workers. There were a history
      of previous TB, TB exposure (mostly from family members) and associated disease
      in 10.3%, 14.2% and 17.4% of cases, respectively. The most encountered associated
      disease was diabetes. The results indicate that TB was most common among non
      working females and was also increased among the men in rural areas, and schools
      seem to be an important source of TB transmission. Thus, an effective control
      program covering the treatment of cases with active disease, such as directly
      observed treatment, and especially preventive measures should be considered to
      control the disease transmission in our region.

PMID- 17203422
TI  - [Pseudomonas aeruginosa colonisation in bronchiectatic patients and clinical
      reflections].
AB  - Bronchiectasis is characterized with irreversible dilatation according to
      destruction of epithelium, elastic and muscular layer. Most important cause of
      bronchiectasis is chronic bacterial infections. Pseudomonas aeruginosa
      colonisation is frequently seen in bronchiectatic patients. We aimed to find out
      P. aeruginosa colonisation frequency and clinical, radiological and spirometric
      reflections due to colonisation. We analysed 83 cases retrospectively. Mean age
      was 58.2 and 54.2% of them were female. Bronchiectasis were localised 19.3% in
      left lung, 19.3% right and 61.4% bilaterally. 29 (35.8%) normal, 28 (34.6%)
      obstructive, 7 (8.6%) restrictive, 17 (21%) mixed type disorders are detected in
      spirometric measures. Sputum culture performed in 50 cases. No microorganism
      colonisation determined in 30 (60%) cases, P. aeruginosa colonisation 16 (32%),
      Haemophilus influenzae 2 (4%), 1 (2%) Streptococcus pneumoniae and Proteus
      mirabilis 1 (2%) cases. P. aeruginosa colonisation determined more frequent in
      males (p<0.05). No significant correlation detected between colonisation and age
      or smoking habits (p>0.05). In cases with colonisation; clubbing and hemoptysis
      were significantly frequent (p<0.05). Only peribronchial thickening was
      significantly correlated with colonisation in radiological findings (p<0.05). In
      blood gase analysis PaO2, oxygen saturation were lower and PaCO2 higher in cases
      colonised with P. aeruginosa but it was not statisticaly significant (p>0.05).
      Hospitalization rate was higher in P. aeruginosa colonised cases (p>0.05). It is
      an important problem about mortality because of higher hemoptysis and
      hospitalisation requirement rate in P. aeruginosa colonised cases.

PMID- 17203423
TI  - [Mersilene mesh-methyl methacrylate sandwich graft reconstruction for repair of
      chest wall defects].
AB  - The diameter of the defect after resection exceeds 5 cm especially in primary
      malignant and metastasis of chest wall tumors and bronchial carcinomas invading
      chest wall. Reconstruction must be performed in cases in which antero-lateral
      chest wall and sternum were resected in order to prevent paradoxical respiration
      caused by chest wall instability and to protect the vital organs from external
      effects. Eight cases undergoing chest wall resection for varying indications and
      reconstruction with methyl methacrylate-mersilene mesh (MM-MM) sandwich graft
      between March 2003 and September 2005 were reviewed. The reconstruction technique
      of MM-MM sandwich graft was compared with other reconstruction materials. Early
      and late postoperative mortality and morbidity ratios of the cases that MM-MM
      sandwich graft performed were compared with the other prosthetic materials in
      literature. All of the patients were extubated in the early postoperative period.
      There were no postoperative mortality and morbidity. Mean hospital stay was 9.6
      days (range, 5-11 days). Mean follow-up was 9 (range, 3-34 months) months
      paradoxical respiration was no observed in whole patients during follow-up
      period. We recommend use of the MM-MM sandwich graft rather than the PTFE graft
      for large defects of the anterolateral chest wall and sternum for successful
      prevention of paradoxical respiration. Additionally, the MM-MM provides better
      cosmetic options, is inexpensive and easy to apply, and offers minimal morbidity.

PMID- 17203424
TI  - Multiple system atrophy presenting with acute respiratory failure due to
      diaphragmatic dysfunction.
AB  - Sleep related respiratory dysfunction and vocal cord paralysis are considered to
      be the major factors responsible for respiratory failure in multiple system
      atrophy (MSA). We report a patient initially presenting with alveolar
      hypoventilation culminating in respiratory failure, ultimately diagnosed as MSA.
      No central sleep apnea or marked paralysis of the vocal cords was noted. The most
      likely cause for the respiratory failure was thought to be the weakness of
      respiratory musculature. This case emphasizes the need that MSA should be added
      to the differential diagnosis of unexplained hypercapnic respiratory failure.

PMID- 17203425
TI  - Peripheral intrapulmonary lipoma: a case report and review of the literature.
AB  - Lipomas are common benign tumours, but intrathoracic lipomas are rare and
      peripheral lung lipomas are exceptionally rare. Eight cases have been described
      in the world literature. We report a case of lipoma arising in the periphery of
      the left lower lung in a 54-year old woman. Grossly, it was presented as a well-
      circumscribed, thinly encapsulated, rounded, pale yellow mass. A wedge resection
      was done of the left lung and the microscopic findings revealed lipoma of the
      lung. The present paper recapitulates the macroscopic and microscopic features,
      the treatment and the differential diagnosis of this rare neoplasm.

PMID- 17203426
TI  - Co-existince of sickle cell disease and hemidiaphragm paralysis.
AB  - Sickle cell anemia is a disease caused by production of abnormal hemoglobin.
      Infection, acute splenic sequestration crisis, aplastic crises, acute chest
      syndrome, stroke, cholelithiasis, renal disease and pain are the major
      complications. Unilateral or bilateral diaphragm paralysis maybe seen following
      phrenic nerve injury and with a variety of motor-neuron diseases, myelopathies,
      neuropathies, and myopathies. Prominent right hemi-diaphragma elevation was
      observed on chest radiograph of a 14 years' old female patient with sickle cell
      disease. Her medical history yielded neither trauma nor intra-thoracic surgery.
      She didn't have either motor deficit or sensation disorder on any region of her
      body. Thorax CT yielded no lesion except the significantly elevated right
      diaphragm. Her cranial CT showed no lesion, too. Diagnosis of right hemidiaphragm
      paralysis was confirmed by positive Hitzenberg Sniff test on fluoroscopy.
      Although several pathophysiologic mechanisms are known to be involved and lead to
      central neurologic complications in sickle cell disease, involvement of
      peripheric nerves have not been reported. Here we present a 14 years' old female
      patient with sickle cell anemia and unilateral diaphragm paralysis, co-existence
      of which have not been reported so far.

PMID- 17203427
TI  - Cardiovascular diseases in obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) affects approximately 5% of women and 15% of men in
      the middle-aged adults, and associated with adverse health outcomes.
      Cardiovascular disturbances are the most serious complications of OSA. These
      complications include heart failure, left/right ventricular dysfunction, acute
      myocardial infarction, arrhythmias, stroke, systemic and pulmonary hypertension.
      All these cardiovascular complications increase morbidity and mortality of OSA.
      Several epidemiologic studies have demonstrated that sleep related breathing
      disorders are an independent risk factor for hypertension, probably resulting
      from a combination of intermittent hypoxia and hypercapnia, arousals, increased
      sympathetic activity, and altered baroreflex control during sleep. Arterial
      hypertension, obesity, diabetes mellitus and coronary artery disease (CAD) which
      are independent predictors of left ventricular dysfunction, often have co
      existence with OSA. Especially severe OSA patients having diastolic dysfunction
      might have an increased risk of heart failure, since diastolic dysfunction might
      be combined with systolic dysfunction. Early recognition and appropriate therapy
      of ventricular dysfunction is advisable to prevent further progression to heart
      failure and death. Patients with acute myocardial infarction, especially if they
      had apneas and hypoxemia without evident heart failure should be evaluated for
      sleep disorders. So, patients with CAD should be evaluated for OSA and vice
      versa. Early recognition and treatment of OSA may improve cardiovascular
      functions. Continuous positive airway pressure (CPAP) applied by nasal mask, is
      still the gold standard method for treatment of the disease and prevention of
      complications.

PMID- 17203428
TI  - Advances in carnivorous plants research.

PMID- 17203429
TI  - Nutrient limitation and stoichiometry of carnivorous plants.
AB  - The cost-benefit model for the evolution of carnivorous plants posits a trade-off
      between photosynthetic costs associated with carnivorous structures and
      photosynthetic benefits accrued through additional nutrient acquisition. The
      model predicts that carnivory is expected to evolve if its marginal benefits
      exceed its marginal costs. Further, the model predicts that when nutrients are
      scarce but neither light nor water is limiting, carnivorous plants should have an
      energetic advantage in competition with non-carnivorous plants. Since the
      publication of the cost-benefit model over 20 years ago, marginal photosynthetic
      costs of carnivory have been demonstrated but marginal photosynthetic benefits
      have not. A review of published data and results of ongoing research show that
      nitrogen, phosphorus, and potassium often (co-)limit growth of carnivorous plants
      and that photosynthetic nutrient use efficiency is 20 - 50 % of that of non
      carnivorous plants. Assessments of stoichiometric relationships among limiting
      nutrients, scaling of leaf mass with photosynthesis and nutrient content, and
      photosynthetic nutrient use efficiency all suggest that carnivorous plants are at
      an energetic disadvantage relative to non-carnivorous plants in similar habitats.
      Overall, current data support some of the predictions of the cost-benefit model,
      fail to support others, and still others remain untested and merit future
      research. Rather than being an optimal solution to an adaptive problem, botanical
      carnivory may represent a set of limited responses constrained by both
      phylogenetic history and environmental stress.

PMID- 17203430
TI  - Recent progress in understanding the evolution of carnivorous lentibulariaceae
      (lamiales).
AB  - Carnivorous plants have emerged as model systems for addressing many ecological
      and evolutionary questions, and since Lentibulariaceae comprise more than half of
      all known carnivorous species (325 spp.), they are of particular interest.
      Studies using various molecular markers have established that Lentibulariaceae
      and their three genera are monophyletic with Pinguicula being sister to a
      Genlisea-Utricularia-clade, while the closest relatives of the family remain
      uncertain. Character states of the carnivorous syndrome in related proto
      carnivorous lamialean families apparently emerged independently. In Utricularia,
      the terrestrial habit has been reconstructed as plesiomorphic, and an extension
      of subgenus Polypompholyx is warranted. In the protozoan-attracting Genlisea,
      subgenus Tayloria is revealed as basal lineage. In Pinguicula, the six major
      lineages found reflect radiations in clearly defined geographic regions, whereas
      most previously recognized subgeneric taxa are non-monophyletic. Genlisea and
      Utricularia exhibit substitutional rates that rank among the highest in
      angiosperms for the molecular markers analyzed. One possible explanation for this
      lies in selective constraints on a wide range of genomic regions that may have
      been lowered due to the use of an alternative mode of acquiring nutrients.

PMID- 17203431
TI  - A new model for the evolution of carnivory in the bladderwort plant
      (utricularia): adaptive changes in cytochrome C oxidase (COX) provide respiratory
      power.
AB  - The evolution of carnivorous plants has been modeled as a selective tradeoff
      between photosynthetic costs and benefits in nutrient-poor habitats. Although
      possibly applicable for pitfall and flypaper trappers, more variables may be
      required for active trapping systems. Bladderwort (utricularia) suction traps
      react to prey stimuli with an extremely rapid release of elastic instability.
      Trap setting requires considerable energy to engage an active ion transport
      process whereby water is pumped out through the thin bladder walls to create
      negative internal pressure. Accordingly, empirical estimates have shown that
      respiratory rates in bladders are far greater than in leafy structures.
      Cytochrome C oxidase (COX) is a multi-subunit enzyme that catalyzes the
      respiratory reduction of oxygen to water and couples this reaction to
      translocation of protons, generating a transmembrane electrochemical gradient
      that is used for the synthesis of adenosine triphosphate (ATP). We have
      previously demonstrated that two contiguous cysteine residues in helix 3 of COX
      subunit I (COX I) have evolved under positive Darwinian selection. This motif,
      absent in approximately 99.9 % of databased COX I proteins from eukaryotes,
      Archaea, and Bacteria, lies directly at the docking point of COX I helix 3 and
      cytochrome C. Modeling of bovine COX I suggests the possibility that a vicinal
      disulfide bridge at this position could cause premature helix termination. The
      helix 3-4 loop makes crucial contacts with the active site of COX, and we
      postulate that the C-C motif might cause a conformational change that decouples
      (or partly decouples) electron transport from proton pumping. Such decoupling
      would permit bladderworts to optimize power output (which equals energy times
      rate) during times of need, albeit with a 20 % reduction in overall energy
      efficiency of the respiratory chain. A new model for the evolution of bladderwort
      carnivory is proposed that includes respiration as an additional tradeoff
      parameter.

PMID- 17203432
TI  - Respiration and photosynthesis of bladders and leaves of aquatic utricularia
      species.
AB  - In aquatic species of carnivorous utricularia, about 10 - 50 % of the total
      biomass consists of bladders. Utricularia bladders are physiologically very
      active organs though their chlorophyll content may greatly be reduced. To specify
      energetic costs of carnivory, respiration (RD) and net photosynthetic rate (PN)
      were compared in bladders and leaves or shoot segments of six aquatic utricularia
      species with differentiated (U. ochroleuca, U. intermedia, U. floridana) or non
      differentiated shoots (U. vulgaris, U. australis, U. bremii) under optimum
      conditions (20 degrees C, [CO (2)] 0.20 mM, 400 micromol m (-2) s (-1) PAR). RD
      of bladders of six utricularia species (5.1 - 8.6 mmol kg (-1)(FW) h (-1)) was 75
      - 200 % greater, than that in leaves in carnivorous or photosynthetic shoots (1.7
      - 6.1 mmol kg (-1)(FW) h (-1)). Within individual species, this difference was
      statistically significant at P < 0.002 - 0.01. However, PN in photosynthetic
      leaves/shoots (40 - 117 mmol kg (-1)(FW) h (-1)) exceeded that in bladders (5.2 -
      14.7 mmol kg (-1)(FW) h (-1)) 7 - 10 times. RD of empty bladders of U. ochroleuca
      was exactly the same as that in bladders containing prey. Though utricularia
      bladders are essential for uptake of growth limiting mineral nutrients N and P
      from prey as the main benefit of carnivory, the current results support previous
      work showing that bladder function requires greater metabolic (maintenance) cost
      and very low photosynthetic efficiency (great RD : PN ratio).

PMID- 17203433
TI  - Smallest angiosperm genomes found in lentibulariaceae, with chromosomes of
      bacterial size.
AB  - Nuclear holoploid genome sizes (C-values) have been estimated to vary about 800
      fold in angiosperms, with the smallest established 1C-value of 157 Mbp recorded
      in Arabidopsis thaliana. In the highly specialized carnivorous family
      Lentibulariaceae now three taxa have been found that exhibit significantly lower
      values: Genlisea margaretae with 63 Mbp, G. aurea with 64 Mbp, and Utricularia
      gibba with 88 Mbp. The smallest mitotic anaphase chromatids in G. aurea have 2.1
      Mbp and are thus of bacterial size (NB: E. coli has ca. 4 Mbp). Several
      Utricularia species range somewhat lower than A. thaliana or are similar in
      genome size. The highest 1C-value known from species of Lentibulariaceae was
      found in Genlisea hispidula with 1510 Mbp, and results in about 24-fold variation
      for Genlisea and the Lentibulariaceae. Taking into account these new
      measurements, genome size variation in angiosperms is now almost 2000-fold.
      Genlisea and Utricularia are plants with terminal positions in the phylogeny of
      the eudicots, so that the findings are relevant for the understanding of genome
      miniaturization. Moreover, the Genlisea-Utricularia clade exhibits one of the
      highest mutational rates in several genomic regions in angiosperms, what may be
      linked to specialized patterns of genome evolution. Ultrasmall genomes have not
      been found in Pinguicula, which is the sister group of the Genlisea-Utricularia
      clade, and which does not show accelerated mutational rates. C-values in
      Pinguicula varied only 1.7-fold from 487 to 829 Mbp.

PMID- 17203434
TI  - Pollination biology of mass flowering terrestrial utricularia species
      (lentibulariaceae) in the Indian Western Ghats.
AB  - The pollination biology of three mass flowering Utricularia species of the Indian
      Western Ghats, U. albocaerulea, U. purpurascens, and U. reticulata, was studied
      for the first time by extensive observation of flower visitors, pollination
      experiments, and nectar analyses. The ephemerality of the Utricularia habitats on
      lateritic plateaus, weather conditions adverse to insects, lack of observations
      of flower visitors to other Utricularia spp., and the predominance of at least
      facultative autogamy in the few Utricularia species studied so far suggested that
      an autogamous breeding system is the common case in the genus. In contrast, we
      showed that the studied populations are incapable of autonomous selfing, or that
      it is an event of negligible rarity, although P/O was similarily low as in
      autogamous species investigated by other authors. In all three species the
      spatial arrangement of the reproductive organs makes an insect vector necessary
      for pollen transfer between and within flowers. However, U. purpurascens and U.
      reticulata are highly self-compatible, which allows for visitor-mediated auto
      selfing and geitonogamy on inflorescence and clone level. Floral nectar is
      present in extremely small volumes in all three species, but sugar concentrations
      are high. More than 50 species of bees, butterflies, moths, hawk moths, and
      dipterans were observed to visit the flowers, and flower morphology facilitated
      pollination by all observed visitors. The results are discussed in the context of
      the phenological characteristics of the studied species, especially the
      phenomenon of mass flowering, and the environmental conditions of their habitats.

PMID- 17203435
TI  - Introduction of a nuclear marker for phylogenetic analysis of Nepenthaceae.
AB  - Nepenthaceae, the pitcher plants of the Old World tropics show a remarkable
      diversity in SE Asia, especially on the islands of Borneo and Sumatra. This
      region is considered as a secondary center of diversity. Sequence analysis of the
      cpDNA TRNK intron supports this hypothesis showing the species of the Malay
      Archipelago as neighbour group to the isolated species from Sri Lanka, the
      Seychelles, and Madagascar. Based on phylogenetic reconstructions an origin of
      recent Nepenthaceae in the Indian subcontinent is assumed. A recent investigation
      focused on a non-plastid, translocated copy of the TRNK intron has revealed an
      incongruence to tree topology based on the cpDNA TRNK intron. Although the
      translocated copy emerged as insufficient for phylogenetic reconstruction of
      Nepenthaceae some taxa showed, contrary to the cpDNA dataset, relatively high
      distances to the rest of the taxa. These results indicated that the phylogeny of
      the TRNK intron could not reflect true phylogenetic relationships. We
      investigated the peptide transferase 1 (PTR1), to develop a phylogenetic marker
      that is based on a nuclear low copy gene in Nepenthes. All sequences obtained
      were probably functional, indicated by the ratio of point mutations of the single
      codon positions in exon and intron regions. Comparative analysis showed that this
      locus is of similar variability as the cpDNA TRNK intron and, contrary to the
      translocated copy of TRNK, potential useful for phylogenetic reconstruction.
      While in parts congruent to the plastid TRNK intron phylogeny, a higher
      divergence of some sequences in PRT1 and in the previously reported, non cpDNA
      dataset indicates that remnants of an older species stock persisted east of
      Wallace's line and on the Sunda Shelf. This suggests that plastid haplotypes
      existing today in the main distribution center of the Nepenthaceae could be
      descendants of more recently dispersed lineages that had been transmitted to an
      old species stock.

PMID- 17203436
TI  - Physicochemical properties of functional surfaces in pitchers of the carnivorous
      plant Nepenthes alata Blanco (Nepenthaceae).
AB  - Pitchers of the carnivorous plant Nepenthes alata are highly specialized organs
      adapted to attract, capture, and digest animals, mostly insects. They consist of
      several well distinguishable zones, differing in macro-morphology, surface
      microstructure, and functions. Since physicochemical properties of these surfaces
      may influence insect adhesion, we measured contact angles of non-polar
      (diiodomethane) and polar liquids (water and ethylene glycol) and estimated the
      free surface energy of 1) the lid, 2) the peristome, 3) the waxy surface of the
      slippery zone, and 4) the glandular surface of the digestive zone in N. alata
      pitchers. As a control, the external surface of the pitcher, as well as abaxial
      and adaxial surfaces of the leaf blade, was measured. Both leaf surfaces, both
      lid surfaces, and the external pitcher surface showed similar contact angles and
      had rather high values of surface free energy with relatively high dispersion
      component. These surfaces are considered to support strong adhesion forces based
      on the capillary interaction, and by this, to promote successful attachment of
      insects. The waxy surface is almost unwettable, has extremely low surface energy,
      and therefore, must essentially decrease insect adhesion. Both the peristome and
      glandular surfaces are wetted readily with both non-polar and polar liquids and
      have very high surface energy with a predominating polar component. These
      properties result in the preclusion of insect adhesion due to the hydrophilic
      lubricating film covering the surfaces. The obtained results support field
      observations and laboratory experiments of previous authors that demonstrated the
      possible role of different pitcher surfaces in insect trapping and retention.

PMID- 17203438
TI  - Preanalytical phase of soluble receptor of transferrin.

PMID- 17203439
TI  - [Visual rating of T2'-blood-oxygen-level-dependent magnetic resonance imaging in
      acute stroke patients--a pilot study].
AB  - PURPOSE: Delineation of brain tissue that is at risk but not yet infarcted
      (penumbra) continues to be a major challenge for stroke imaging. Metabolic
      characterization of the penumbra might be able to be achieved using blood-oxygen
      level-dependent (BOLD) imaging. MATERIALS AND METHODS: We analyzed MRI data from
      20 patients within the first 6 hours after stroke onset and after 5-8 days. Among
      other sequences, the MRI protocol consisted of diffusion-weighted (DWI/ADC =
      apparent diffusion coefficient) and quantitative T2 and T2* imaging (qT2, qT2*).
      BOLD images (T2') were calculated using 1/T2' = 1/qT2* - 1/qT2. BOLD lesions were
      rated by two blinded observers. RESULTS: Based on the primary blinded reading of
      the BOLD images, the lesion side was rated correctly by observers 1 and 2 in
      80/50 % of the cases, incorrectly in 5/40 % of the cases, and rated as not
      visible in 15/10 % of the cases. After unblinding the observers, the visibility
      was rated in 45/45 % of the cases as good, in 35/40 % of the cases as reasonable,
      and in 20/15 % of the cases as insufficient for diagnostic purposes. The
      sensitivity for subsequent infarct growth was 0.88 (95 % confidence interval, CI
      0.47 to 0.99), the specificity was 0.33 (95 % CI 0.07 to 0.70), the positive
      predictive value (PPV) was 0.54 (95 % CI 0.25 to 0.81), and the negative
      predictive value (NPV) was 0.75 (95 % CI 0.19 to 0.99). The odds ratio for
      subsequent infarct growth was 3.5 (95 % CI 0.20 to 115.53). CONCLUSION: Hypo
      intense lesions in BOLD imaging were visible and exceeded the lesion in diffusion
      weighted imaging in most of the stroke patients. The encouraging results justify
      further testing of the hypothesis that BOLD lesions, when larger than DWI
      lesions, are associated with infarct growth from initial DWI to final infarct.

PMID- 17203440
TI  - [Patterns of delayed-enhancement in MRI of ischemic and non-ischemic
      cardiomyopathies].
AB  - Contrast-enhanced MRI using the delayed-enhancement technique (DE-MRI) is widely
      applied in the clinical work-up of myocardial diseases. Myocardial diseases of
      varying etiology result in myocardial changes, such as necrosis, fibrosis, edema
      and metabolite deposition, which can be visualized by DE-MRI. Acute and chronic
      ischemic diseases based on a coronary artery disease as well as non-ischemic
      cardiomyopathies display DE. Cardiomyopathies often show a characteristic
      enhancement pattern. While ischemic lesions are localized in the subendocardium,
      non-ischemic cardiomyopathies often display an intramyocardial or subepicardial
      pattern. The typical pattern for dilated cardiomyopathies is band-like and
      intramyocardial with septal involvement. Arrhythmogenic right-ventricular
      dysplasias/cardiomyopathies are frequently associated with right-ventricular DE.
      In the case of amyloid cardiomyopathies which are often restrictive
      cardiomyopathies, subendocardial and circular DE is typically observed.
      Hypertrophic cardiomyopathies display patchy intramyocardial DE usually in the
      anteroseptal region. Acute myocarditis is typically accompanied by
      intramyocardial or subepicardial DE affecting the lateral wall. In the case of
      chronic myocarditis, intramyocardial or subepicardial DE is observed most
      frequently. Cardiac sarcoidosis typically entails patchy subepicardial DE with
      right- and left-ventricular involvement. Since there is an overlap between the
      enhancement patterns of cardiomyopathies, the diagnostic accuracy of DE-MRI is
      limited and the diagnosis must be based on additional clinical and MRI findings.
      The amount of DE often corresponds with cardiac functional parameters as well as
      with the frequency of cardiac events so that DE-MRI may be useful for risk
      stratification. Furthermore, DE-MRI can be helpful in the planning and evaluation
      of myocardial biopsies and electrophysiological examinations.

PMID- 17203441
TI  - [Portal vein embolization preparation for major hepatic resection: a new standard
      in liver surgery].
AB  - Preoperative portal vein embolization (PVE) is increasingly used for operative
      treatment of patients scheduled to undergo liver resection when the volume of the
      future remnant liver appears to be insufficient. Portal vein embolization should
      be considered when the prospective postoperative liver volume is less than 20 %
      or less than 40 % in patients with known liver cirrhosis. Our own results (n =
      28) demonstrated an average volume increase in segments II and III of 280 +/- 95
      ml to 420 +/- 98 ml within 6 weeks after selective percutaneous- transhepatic
      embolization of the portal vein branches (IV)-V-VIII. Thus, an expanded right
      resection of the liver could be performed in all patients without major
      complications. None of the patients suffered from clinically relevant liver
      insufficiency within the first few postoperative months.

PMID- 17203442
TI  - [Determination of the effective dose for CT examinations and influence of the
      setup parameters].
AB  - PURPOSE: CT examinations are considered to be high dose applications in radiation
      diagnostics. Consequently, radiation exposure and its potential reduction are an
      important issue. The aim of this paper is to determine effective doses for CT
      examinations under clinical conditions. The effective doses were determined from
      organ dose measurements with an optimal amount of effort. MATERIALS AND METHODS:
      The measured point doses in the various organs in an anthropomorphic phantom were
      weighted with respect to morphology and location in the radiation field and were
      averaged to obtain the organ doses. These doses together with the individual
      radiation sensitivities were able to be used to calculate the effective dose. The
      following examinations were taken into consideration: thorax, abdomen and skull.
      Only one parameter was changed for each measurement (the high voltage of the X
      ray tube, the pitch, the collimation, or the automatic adjustment of the tube
      current to correct the individual absorption in the phantom). RESULTS: The
      effective doses for the thorax examinations were between 5 and 7 mSv, and for the
      abdomen between 8 and 15 mSv depending on the technique and parameters. In some
      of the organs the organ doses can be in excess of 25 mSv. Our results were
      compared to the corresponding results of two commercial computer programs for
      dose calculations. The calculated effective doses generally showed lower values.
      CONCLUSION: It is possible to determine the effective dose from 24-point dose
      measurements by optimizing the choice of measuring location in the phantom. The
      individual adaptation of parameters such as tube voltage, exposure, pitch,
      collimated slice thickness, and investigation volume must be taken into
      consideration from case to case.

PMID- 17203443
TI  - [Radiologic evaluation of cup placement variation in conventional total hip
      arthroplasty].
AB  - PURPOSE: Determination of the amount of variation in conventional acetabular cup
      positioning (radiological inclination and anteversion) in view of different
      factors that could influence the measured angles. MATERIALS AND METHODS: The
      intended acetabular cup position of 45 degrees inclination and 20 degrees
      anteversion was checked radiologically in 950 patients who received a cementless
      total hip replacement. The qualifications of the surgeon, operated side and
      implant model were recorded and analyzed with respect to a possible correlation
      with the results. Since a "safe angle" cannot be defined without consideration of
      other variables, a tolerable deviation of the target position was investigated.
      RESULTS: The mean inclination angle was 48.7 degrees (SD 7 degrees, minimum 28
      degrees, maximum 75 degrees ). Anteversion was measured with a mean of 18.6
      degrees (SD 9 degrees, minimum -9 degrees, maximum 50 degrees ). Assuming an
      acceptable deviation of +/- 5 degrees from the target position (45 degrees
      inclination and 20 degrees anteversion), only 22.7 % of the acetabular cups were
      in this range. In the case of an acceptable deviation of +/- 10 degrees, 34.5 %
      of the cups were still outside of the acceptable range. The qualifications of the
      surgeon, the implanted model, as well as the operated side did not have a
      significant influence on the results. CONCLUSION: The common implantation
      technique yielded significant variation with respect to anteversion and
      inclination. The application of computer-aided navigation in the placement of
      acetabular cups would help to improve accuracy and reproducibility considerably
      in total hip arthroplasty.

PMID- 17203444
TI  - [Is the application of CAD useful for radiologists for passing the official tests
      required for outpatient breast imaging?].
AB  - PURPOSE: To analyze whether currently available CAD systems meet the diagnostic
      requirements for passing screening tests (first reader CAD) and to analyze
      whether the additional usage of CAD systems provides significant support for the
      diagnosing radiologist on the basis of official screening test cases (second
      reading by CAD). MATERIAL AND METHODS: 200 images of 100 mammographies of 50
      patients of an official screening test case collection were analyzed double-blind
      with and without CAD printouts (iCAD, USA ) by three radiologists: one
      experienced in breast analysis and CAD application, one experienced in
      mammography analysis but inexperienced in CAD usage, one with minimal experience
      with breast analysis and CAD application. All radiologists measured the largest
      diameter of any malignant mass. The mean value of these calculations was
      correlated to the largest diameter given by CAD prompts. RESULTS: The mean
      sensitivity and specificity increased slightly as a result of the additional
      usage of CAD (1 and 0.6 %, resp.). Both values are not statistically significant.
      The highest effect was measured for the radiologist with CAD experience, while no
      effect was measured for the inexperienced radiologist. CAD met the sensitivity
      requirements but not the specificity criteria (96 and 20.3 %, resp.). The sizes
      given by CAD prompts corresponded significantly with the real sizes (r = 0.45, p
      < 0.05). CONCLUSION: A statistically significant effect of the use of CAD could
      not been detected dependent on the radiological experience or the CAD experience.
      The effect of CAD on radiologists is still subtle despite the highly sensitive
      CAD performance due to the high number of false positive prompts and thus does
      not reach statistical significance. Sizes given by CAD prompts correlate
      significantly with the real sizes of malignant lesions.

PMID- 17203445
TI  - [Osteodensitometry in children and adolescents with inflammatory bowel disease].
AB  - PURPOSE: To evaluate the quantity and severity of bone disorders in children and
      adolescents with inflammatory bowel diseases (IBD) and to examine the correlation
      to whole body growth. MATERIALS AND METHODS: In this study 89 bone mineral
      density measurements were performed and retrospectively analyzed. RESULTS: Under
      consideration of growth retardation, over 65.2 % of the patients with Cohn's
      disease showed a reduced bone mineral density. Osteopenia/Osteoporosis is seldom
      seen in patients with ulcerative colitis, i. e., only 34.8 % showed a reduction
      in bone mineral density. Growth retardation and reduced bone mineral density are
      correlated. Patients with Cohn's disease and a body length below the 25th height
      percentile showed a reduced bone mineral density in 78.1 % of the cases. Patients
      with a body length below the 10th height percentile had a reduced bone mineral
      density in 83.3 % of the cases. CONCLUSION: These results demonstrate the value
      of osteodensitometric measurements in patients with chronic diseases, especially
      in children and adolescents with inflammatory bowel disease.

PMID- 17203446
TI  - [Prospective comparison of different ultrasound modalities to measure thicknesses
      less than 1 mm].
AB  - PURPOSE: New ultrasound techniques with improved visualization and better
      transducers constantly expand the methods of measurement. In the border area in
      the case of thickness measurements of less than 1 millimeter, e. g. the
      measurement of the "Intima-Media Thickness" (IMT), it is not clear if better
      visualization comes at the price of incorrect measurement values. We checked
      different modalities for accuracy and visualization quality. MATERIALS AND
      METHODS: We prospectively examined the IMT of obese children using different
      ultrasound modalities. The image quality was evaluated by two independent
      pediatric radiologists. A phantom with an exact thickness of 0.3 mm (value of the
      thinnest measured IMT thickness) was subsequently created by precision engineers.
      Measurements were carried out and analyzed using fundamental ultrasound, tissue
      harmonic imaging, speckle reduction imaging and cross beam (real-time compound)
      imaging. RESULTS: The best image quality was reached using speckle reduction
      imaging. This technique and fundamental ultrasound produced the most exact data.
      However, the recognizability was worse in fundamental ultrasound than in speckle
      reduction imaging. CONCLUSION: Speckle reduction imaging appears to be the best
      technique for measuring thicknesses less than 1 mm.

PMID- 17203447
TI  - [Scapular-thoracic dissociation with fatal outcome].

PMID- 17203448
TI  - [Egalitarian and individualistic perceptions of fairness in health care
      provision: results from a survey of patients and students].
AB  - OBJECTIVE: This study focuses on the following question: How are health care
      reform proposals accepted by different groups of insured persons? Two perceptions
      of justice or fairness are compared. The "egalitarian view" states that the
      financial burden should be distributed as equally as possible across all insured
      persons and that health care should be offered to all insured persons in the same
      way. The "individualistic view" states that health care should be provided
      according to the individual's willingness to pay for it, and also according to
      the individual health behaviour. METHODS: In 2003, a standardised questionnaire
      was answered by a random sample of 343 persons (175 elderly patients and 168
      students). The egalitarian view was assessed by four questions and the
      individualistic view by five questions. The questionnaire included vignettes.
      Based on this method it is possible to assess if an answer depends on the "frame"
      that is presented as an example (framing the question as: thinking of a poor or a
      wealthy person). RESULTS: A bivariate analyses show that the egalitarian view is
      mostly present in the following groups of patients: higher age group, insured in
      a Statutory Sickness fund, high medication, many physician visits. Concerning
      students, this view is also associated with low physical activity. The
      individualistic view can be found mostly in the following groups of patients:
      male, insured in a private health insurance, higher educational level, employed,
      high physical activity, non-smoker. Concerning students, very similar
      associations can be seen. These results are largely confirmed by multivariate
      analyses. It can also be seen that the answers are strongly influenced by the
      vignettes. DISCUSSION: The insured persons seem to approve or disapprove of
      health care reform proposals according to their personal characteristics. The
      overall acceptance of health care reforms will largely depend on the ability to
      integrate these different perspectives.

PMID- 17203449
TI  - [Personal contextual factors, part I].
AB  - The International Classification of Functioning, Disability and Health (ICF) does
      not yet classify personal contextual factors. To determine the interaction of
      these factors on activities and participation of a person as well as their
      influence on the probable outcome of interventions, they must be taken into
      account in individual sociomedical expertises. Therefore, a group of medical
      experts working for the social health insurance medical advisory boards in
      Germany compiled a proposal for a systematic classification of personal
      contextual factors into domains, categories and items with respect to the ethical
      guidelines of the ICF. In a second step the main issues were transferred into the
      preliminary draft for a short version which will be published later to give
      support for practical daily use in health insurance matters.

PMID- 17203450
TI  - [Differences in small area prevalence of respiratory diseases in children:
      challenges of an investigation initiated by parents].
AB  - OBJECTIVE: The aim of our study was to assess the prevalence of respiratory
      diseases in children living in a rural area in Bavaria in a systematic and
      standardised way to clarify whether a disease cluster exists. Reports from a
      parents' initiative claiming an increase of diseased children and assuming an
      association with air pollution due to nearby industrial sources and heavy traffic
      were the reason for the study. METHODS: Parents of all children living in small
      towns specified by the parents' initiative as affected region (central area) and
      parents of those children aged 6-7 or 13-14 years living in adjacent areas
      (control area) were asked to complete a written questionnaire. In bivariate
      analysis, differences in prevalences between the central area and the control
      area were assessed by the chi (2) test. In multivariate analysis, confounder
      adjusted odds ratios with 95 % confidence intervals were calculated by logistic
      regression. In addition, generalized linear mixed models were used to control for
      potential clusters in families. RESULTS: The response rate was rather low (total
      46 %, central area 53 %, control area 34 %). The study population comprised 121
      girls and 141 boys. There was a pattern of increased prevalences of cough, wheeze
      and respiratory diseases caused by infections in children living in the central
      area compared to the control area. However, statistical significance was rarely
      observed. No systematic differences were observed for the prevalence of allergic
      rhinitis and atopic dermatitis. Selection bias due to varying response rates in
      the central versus the control area and information bias introduced by the
      preceding intensive public discussion could not be excluded. The comparison of
      prevalences detected in the small area with published data from other
      epidemiological studies in Germany did not indicate a systematically increased
      prevalence of respiratory symptoms or physician-diagnosed respiratory diseases in
      children from the whole area as well as in children from the central area only.
      CONCLUSION: This study exemplifies the challenges of small area investigations
      initiated by the residential community to clarify an assumed disease cluster
      caused by environmental pollution. The prior comparison of small area prevalence
      data with results of other epidemiological studies aids the decision making as to
      whether a detailed study with comprehensive assessment of individual exposure is
      justifiable.

PMID- 17203451
TI  - [New forms of management in dermatology. Integrated in-patient-out-patient
      prevention of severe occupational dermatoses: cornerstones for an effective
      integrated management in clinics and practices].
AB  - Occupational dermatoses (OD) are the most frequent occupational diseases in
      Germany and amount to more than 25% of all suspected occupational diseases.
      Preventive measures have proven to be very effective in recent years, especially
      measures of primary and secondary prevention as components of a complex
      hierarchical prevention concept in wet work occupations. If employees are in
      danger of loosing their job due to a severe OD, intensive interdisciplinary
      measures of tertiary individual prevention (TIP) are required. TIP comprises 2-3
      weeks of in-patient treatment plus intensive health-pedagogic counselling,
      followed by 3 consecutive weeks (or longer) of out-patient treatment by the local
      dermatologists ("Osnabrueck model"). Each patient will stay off work for a total
      of at least 6 weeks to allow full barrier-recovery. It could be shown that 2/3 of
      the patients successfully remained in their workplaces because of TIP. TIP
      reveals remarkable pertinent options for interdisciplinary disease management in
      severe OD in all risk professions. In Germany recently, a multi-centre study was
      started which will further standardise such preventive measures and evaluate
      their long-term success.

PMID- 17203452
TI  - [Tick bites and borreliosis in children attending forest kindergarten: a
      challenge for prevention].
AB  - AIM: The aim of this study was to analyse the influence of preventive measures on
      the risk of being bitten by a tick and of suffering from borreliosis in children
      attending so-called 'forest kindergartens' (nurseries located in forested areas
      where children spend all-season full-time outdoors), compared to children
      attending regular kindergartens. In addition, we aimed to analyse sources of
      information and the risk of being bitten more than once. METHODS: 53
      kindergartens (25 forest kindergartens, 28 regular kindergartens) in the state of
      Baden-Wurttemberg, Germany participated in this study and protective parental
      behaviour was recorded. In a prospective cohort study, the numbers of tick bites
      and cases of borreliosis were recorded monthly (March to October 2004) using a
      questionnaire. The influence of preventive measures was estimated using
      multivariate log-binomial regression. RESULTS: Altogether, 1707 children of
      'forest kindergartens' (506 children) and regular kindergartens (1201 children)
      were included. Parental protective behaviour was significantly better in forest
      kindergartens compared to regular kindergartens. There were no substantial
      differences between effect estimates after stratification for parental protective
      behaviour. For children attending a 'forest kindergarten, the adjusted risk ratio
      of being tick bitten was 2.6 (3.3-3.0) which was only slightly different from the
      unadjusted risk, ratio. CONCLUSION: Although protective parental behaviour in
      'forest kindergarten' children was significantly better compared to regular
      kindergarten, children in forest kindergartens are at a considerable risk of tick
      bites and borreliosis. Implementing effective preventive measures against
      borreliosis represents a public health challenge.

PMID- 17203453
TI  - [Nursing science courses at the University of Basel/Switzerland. Concept,
      guidelines, curriculum and evaluation of study results].
AB  - Since 2000 the University of Basel offers the first Bachelor-Master's education
      in nursing science in Switzerland. The structure, content, faculty and students
      of this BSN-MSN curriculum are described. An evaluation study on the basis of
      quantitative and qualitative data drawn from students (n = 50) and alumni,
      respectively (n = 15), assesses strengths and weaknesses of this new education.

PMID- 17203454
TI  - [Older soil contaminations and human biomonitoring--two typical examples].
AB  - AIM: A health risk assessment of inhabitants had to be accomplished in two areas
      of former color production works, which had caused considerable soil
      contaminations predominantly with arsenic and lead. METHODS: Samples of soil,
      blood and urine were analysed during orientation and detail investigations
      according to the German soil protection laws. RESULTS: The soil investigations
      revealed high contaminations in some parts of the two areas (maximum
      concentrations 550 mg arsenic/kg and 9100 mg lead/kg in residential topsoil from
      depths of 0-35 cm). Contrary to these findings, arsenic levels in the urine and
      lead levels in the blood of most of the residents were lower than the reference
      values for the common German population (arsenic 15 microg/L, lead 50-90
      microg/L). In some cases of elevated biological concentrations, other sources of
      exposure could be detected like drinking tea from a tea-pot with a lead
      containing glaze or drinking water from a highly contaminated garden well;
      interventional measures resulted in major decreases in the internal loads of
      these people. CONCLUSIONS: The investigations clearly showed that an exposure via
      the pathway soil--water--human can be of serious health concern whereas older
      soil contaminations are seemingly of low relevance with regard to the direct
      contact of persons during daily life on those areas. Therefore, it is recommended
      to increase the soil examination values ("Prufwerte") of the German soil
      protection laws by a default factor of 2 or 3 in cases of soil contaminations
      older than 20 years.

PMID- 17203455
TI  - [Code of conduct--good practice for research in health care financed by third
      parties].

PMID- 17203457
TI  - [Compensation for tinnitus in private accident insurance].
AB  - According to the provisions of private accident insurance, mental or psychic
      reactions are excluded from compensation. Until now, tinnitus was taken as fully
      psychic and therefore excluded. In two recently published judgments of the
      Federal Supreme Court in Germany the assessment of tinnitus in private accident
      insurance and particularly the exclusion clause section sign 2 Abs. 4 AUB 88 has
      been newly defined. According to this actual jurisdiction the compensation of
      tinnitus could be possible, when as physical underlying reason a proved harm in
      the inner ear or the auditory pathway (hearing loss), which can be traced back to
      the accident according to the rules of causality. This leads to the question how
      Tinnitus could be compensated without modification of the general terms and
      conditions of the private accident insurance. A compensating table is proposed,
      which recognizes the somatic (physical) part of tinnitus and is based on medical
      and scientific findings of the relation between hearing loss and tinnitus.

PMID- 17203459
TI  - ZFHX1B mutations in patients with Mowat-Wilson syndrome.
AB  - Mowat-Wilson syndrome (MWS) is a recently delineated mental retardation (MR)
      multiple congenital anomaly syndrome, characterized by typical facies, severe MR,
      epilepsy, and variable congenital malformations, including Hirschsprung disease
      (HSCR), genital anomalies, congenital heart disease (CHD), and agenesis of the
      corpus callosum (ACC). It is caused by de novo heterozygous mutations or
      deletions of the ZFHX1B gene located at 2q22. ZFHX1B encodes Smad-interacting
      protein-1 (SMADIP1 or SIP1), a transcriptional corepressor involved in the
      transforming growth factor-beta signaling pathway. It is a highly evolutionarily
      conserved gene, widely expressed in embryological development. Over 100 mutations
      have been described in patients with clinically typical MWS, who almost always
      have whole gene deletions or truncating mutations (nonsense or frameshift) of
      ZFHX1B, suggesting that haploinsufficiency is the basis of MWS pathology. No
      obvious genotype-phenotype correlation could be identified so far, but atypical
      phenotypes have been reported with missense or splice mutations in the ZFHX1B
      gene. In this work we describe 40 novel mutations and we summarize the various
      mutational reports published since the identification of the causative gene.

PMID- 17203460
TI  - Sensory filtering phenomenology in PTSD.
AB  - Disrupted sensory filtering, or problems with suppressing irrelevant
      environmental sensory stimuli, has been reported in individuals with
      posttraumatic stress disorder (PTSD). However, the relationship of sensory
      filtering deficits to specific PTSD symptoms versus an association with general
      trauma exposure is unclear. These relationships were examined by administering
      self-report measures of trauma exposure, PTSD, and sensory gating phenomenology
      to undergraduate participants with PTSD (n=32), with trauma history but without
      PTSD (n=144), and with minimal trauma history (n=153). Subjects with PTSD
      reported greater filtering disruption than individuals in the trauma only and low
      trauma groups, who did not differ. Individuals endorsing reexperiencing and
      numbing symptoms, and females endorsing hypervigilance, reported disrupted
      sensory filtering phenomenology. These results suggest that impaired filtering
      differentiates between individuals with PTSD symptoms and asymptomatic
      individuals exposed to multiple traumas and low-trauma controls.

PMID- 17203461
TI  - Reversed diastolic flow in the uterine artery - a new Doppler finding related to
      placental insufficiency?
AB  - Increased uterine artery pulsatility and resistance indices with or without
      notching of the waveform have been associated with an increased risk of pre
      eclampsia and fetal growth restriction. However, reversed diastolic flow in the
      uterine artery has not previously been reported. We present two high-risk
      obstetric cases complicated by severe placental insufficiency: pre-eclampsia
      followed by eclampsia in one case and intrauterine growth restriction with
      abnormal cardiotocography in the other. Doppler studies of the uterine arteries
      revealed reversed diastolic flow in both cases. The pathophysiology and potential
      implications are discussed.

PMID- 17203462
TI  - Evidence for a critical role of entorhinal cortex at pre-exposure for latent
      inhibition disruption in rats.
AB  - Latent inhibition (LI), that is the decrease in conditioned response induced by
      the repeated nonreinforced pre-exposures to the to-be-conditioned stimulus, is
      disrupted by entorhinal cortex (EC) lesions. The mechanism involved in this
      disruption is unknown, and in particular the experimental stage (pre-exposure or
      conditioning) at which the integrity of EC is necessary has to be determined. The
      purpose of this study was to address this issue by using reversible inactivation
      of the EC by local micro-infusion of tetrodotoxin (TTX). TTX was infused either
      before the pre-exposure phase, before the conditioning phase, or before both
      phases. LI was unaffected in rats that received TTX before conditioning or before
      both pre-exposure and conditioning. In contrast, LI was disrupted in rats that
      received TTX before pre-exposure only. These results are discussed in the
      framework of LI models.

PMID- 17203463
TI  - Roscovitine-activated HIP2 kinase induces phosphorylation of wt p53 at Ser-46 in
      human MCF-7 breast cancer cells.
AB  - Human MCF-7 breast cancer cells are relatively resistant to conventional
      chemotherapy due to the lack of caspase-3 activity. We reported recently that
      roscovitine (ROSC), a potent cyclin-dependent kinase 2 inhibitor, arrests human
      MCF-7 breast cancer cells in the G(2) phase of the cell cycle and concomitantly
      induces apoptosis. Exposure of MCF-7 cells to ROSC also strongly activates the wt
      p53 tumor suppressor protein in a time- and dose-dependent manner. The p53 level
      increased despite upregulation of Hdm-2 protein and was attributable to the site
      specific phosphorylation at Ser-46. The p53 protein phosphorylated at serine 46
      causes the up-regulation of the p53AIP1 protein, a component of mitochondria. In
      the present study we identified the pathway mediating ROSC-induced p53
      activation. Exposure of MCF-7 cells to ROSC activated homeodomain-intereacting
      protein kinase-2 (HIPK2). The overexpression of wild-type but not kinase inactive
      HIPK2 increased the basal and ROSC-induced level of p53 phosphorylation at Ser-46
      and strongly enhanced the rate of apoptosis in cells exposed to ROSC. We show
      that HIPK2 is activated by ROSC and mediates ROSC-induced P-Ser-46-p53, thereby
      stabilizing wt p53 and increasing the efficacy of drug-induced apoptosis in MCF-7
      cells. These results identify HIPK2 as a component of the ROSC-induced signaling
      pathway leading to the stabilization and activation of wt p53 protein.

PMID- 17203464
TI  - cAMP-dependent protein kinase enhances inositol 1,4,5-trisphosphate-induced Ca2+
      release in AR4-2J cells.
AB  - In non-excitable cells, the inositol 1,4,5-trisphosphate receptor (IP(3)R), a
      ligand-gated Ca(2+) channel, plays an important role in the control of
      intracellular Ca(2+). There are three subtypes of IP(3)R that are differentially
      distributed among cell types. AR4-2J cells express almost exclusively the IP(3)R
      2 subtype. The purpose of this study was to investigate the effect of cAMP
      dependent protein kinase (PKA) on the activity of IP(3)R-2 in AR4-2J cells. We
      showed that immunoprecipitated IP(3)R-2 is a good substrate for PKA. Using a back
      phosphorylation approach, we showed that endogenous PKA phosphorylates IP(3)R-2
      in intact AR4-2J cells. Pretreatment with PKA enhanced IP(3)-induced Ca(2+)
      release in permeabilized AR4-2J cells. Pretreatment with the cAMP generating
      agent's forskolin and vasoactive intestinal peptide (VIP) enhanced carbachol
      (Cch)-induced and epidermal growth factor (EGF)-induced Ca(2+) responses in
      intact AR4-2J cells. Our results are consistent with an enhancing effect of PKA
      on IP(3)R-2 activity. This conclusion supports the emerging concept of crosstalk
      between Ca(2+) signaling and cAMP pathways and thus provides another way by which
      Ca(2+) signals are finely encoded within non-excitable cells.

PMID- 17203465
TI  - The immunosuppressant FTY720 inhibits tumor angiogenesis via the sphingosine 1
      phosphate receptor 1.
AB  - FTY720, a sphingosine 1-phosphate (S1P) analog, acts as an immunosuppressant
      through trapping of T cells in secondary lymphoid tissues. FTY720 was also shown
      to prevent tumor growth and to inhibit vascular permeability. The MTT
      proliferation assay illustrated that endothelial cells are more susceptible to
      the anti-proliferative effect of FTY720 than Lewis lung carcinoma (LLC1) cells.
      In a spheroid angiogenesis model, FTY720 potently inhibited the sprouting
      activity of VEGF-A-stimulated endothelial cells even at concentrations that
      apparently had no anti-proliferative effect. Mechanistically, the anti-angiogenic
      effect of the general S1P receptor agonist FTY720 was mimicked by the specific
      S1P1 receptor agonist SEW2871. Moreover, the anti-angiogenic effect of FTY720 was
      abrogated in the presence of CXCR4-neutralizing antibodies. This indicates that
      the effect was at least in part mediated by the S1P1 receptor and involved
      transactivation of the CXCR4 chemokine receptor. Additionally, we could
      illustrate in a coculture spheroid model, employing endothelial and smooth muscle
      cells (SMCs), that the latter confer a strong protective effect regarding the
      action of FTY720 upon the endothelial cells. In a subcutaneous LLC1 tumor model,
      the anti-angiogenic capacity translated into a reduced tumor size in syngeneic
      C57BL/6 mice. Consistently, in the Matrigel plug in vivo assay, 10 mg/kg/d FTY720
      resulted in a strong inhibition of angiogenesis as demonstrated by a reduced
      capillary density. Thus, in organ transplant patients, FTY720 may prove
      efficacious in preventing graft rejection as well as tumor development.

PMID- 17203466
TI  - Effect of unitization on associative recognition in amnesia.
AB  - We examined how associative recognition performance in amnesic patients is
      mediated by use of a unitized (i.e., holistic) encoding strategy, and the degree
      to which the unitization effect is related to sparing of familiarity-based
      recognition. Participants studied word pairs as either separate lexical units in
      sentences (i.e., nonunitized) or as compounds (unitized). Under standard
      recognition instructions, normal controls and patients with left-temporal lobe
      damage (previously determined to have impairments in both recollection and
      familiarity) showed no difference for unitized and nonunitized pairs, whereas
      hypoxics (previously determined to have impaired recollection but relatively
      preserved familiarity) showed an advantage of unitized over nonunitized pairs.
      This effect was reproduced in normal healthy participants under instructions to
      restrict responses to judgments of familiarity. The results indicate that
      unitization may mediate the degree of associative recognition impairment
      exhibited by some amnesic patients, and that the effect is related to preserved
      familiarity capacity. The relevance of the results to the debate over the
      importance of the hippocampus in memory for associations is discussed.

PMID- 17203467
TI  - Caloric restrictions affect some factors involved in age-related
      hypercholesterolemia.
AB  - Ageing has been defined as a progressive decrease in physiological capacity and a
      reduced ability to respond to environmental stresses. It has been observed that
      diet-restricted animals show a minor morbidity in age-related disease. Among
      these age-related diseases, hypercholesterolemia is the most recurring one and it
      is often associated with cardiac failure. Several studies have been published
      indicating age-dependent changes in circulating levels of cholesterol in both
      humans and in rodents; recently changes have also been reported in the proteins
      involved in cholesterol homeostasis, that is, 3-hydroxy-3-methylglutaryl coenzyme
      A reductase (HMG-CoAR), Insig-induced gene (Insig) protein, SREBP cleavage
      activating protein (SCAP), sterol regulatory element binding protein (SREBP), and
      low density lipoprotein receptor (LDLr). Most age-related modifications of
      biochemical parameters are normalized or very improved in food-restricted
      animals, so the aim of this work is to examine whether or not alterations of the
      factors involved in cholesterol homeostasis which occur during ageing could be
      counteracted by caloric restriction (CR). The data show that the diet
      restrictions used attenuate the age-related effects on the factors involved in
      the synthesis and the degradation rate of HMG-CoAR; in spite of this, CRs have a
      good effect on the age-related hypercholesterolemia whose reduction seems to
      depend both on the correct membrane LDLr localization and on the proper restored
      HMG-CoAR activity.

PMID- 17203468
TI  - Opposite effects of high glucose on MMP-2 and TIMP-2 in human endothelial cells.
AB  - Diabetes mellitus (DM) is a major risk factor for atherosclerosis and causes
      multiple cardiovascular complications. Although high glucose can induce matrix
      metalloproteinases (MMPs), its inhibitors and cell apoptosis, little is known
      about the roles of MMPs in regulating cell apoptosis in response to high glucose.
      To address this issue, we elucidated the relationship between MMPs, its
      inhibitors and cell apoptosis in human umbilical vein endothelial cells (HUVECs).
      HUVECs were treated with medium containing 5.5 mM or 33 mM of glucose in the
      presence or the absence of ascorbic acid and MMP inhibitors (GM6001 and
      endogenous tissue inhibitors of MMPs, TIMP-1, and TIMP-2). For detection of cell
      apoptosis, the cell death detection ELISA assay was used. The results revealed
      that high glucose-induced apoptosis could be suppressed by ascorbic acid, GM6001
      and TIMP-2, but not by TIMP-1. The activities of MMP-2, MMP-9 and its inhibitors,
      TIMP-1, TIMP-2 after high glucose treatment, were also detected by ELISA method.
      We found that the activated form of MMP-2, but not MMP-9, was increased, while
      the level of TIMP-2, but not TIMP-1, was decreased. In Western blot and RT-PCR
      analysis, the expression of TIMP-2, but not TIMP-1, after high glucose treatment
      was downregulated, whereas the levels of MMP-2 and -9 proteins and mRNA were not
      changed. The present study indicated that oxidative stress induced by high
      glucose might be involved in the opposite effects on MMP-2 activation and TIMP-2
      downregulation. This reactive oxygen species (ROS)-dependent MMP-2 activation in
      turn mediates high glucose-induced cell apoptosis in HUVECs.

PMID- 17203469
TI  - Complementary effects of thienopyridine pretreatment and platelet glycoprotein
      IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention;
      results from the ESPRIT trial.
AB  - OBJECTIVES: This analysis sought to investigate the complementary effect of
      thienopyridine pretreatment and platelet glycoprotein (GP) IIb/IIIa integrin
      blockade in coronary stent intervention. BACKGROUND: Definitive evidence
      supporting combined antiplatelet therapy consisting of thienopyridine
      pretreatment and GP IIb/IIIa receptor blockade in patients undergoing
      percutaneous coronary intervention (PCI) with stent implantation is limited.
      METHODS: We retrospectively analyzed clinical outcomes by thienopyridine use in
      the 2,040 patients randomized to eptifibatide or placebo who underwent PCI in the
      ESPRIT trial. RESULTS: A total of 901 patients received a loading dose of
      thienopyridine before PCI (group 1), 123 received thienopyridine pretreatment
      without a loading dose (group 2), and 1,016 were not treated with thienopyridine
      before PCI (group 3). The composite incidence of death or myocardial infarction
      at 30 days was significantly lower in group 1 than in groups 2 and 3 combined
      (OR, 0.71 [95%CI, 0.52-0.99]; P = 0.0417). A similar trend was seen for the
      composite of death, myocardial infarction, or urgent target vessel
      revascularization (unadjusted OR, 0.77 [0.57-1.05]; P = 0.1025). After adjusting
      for baseline characteristics, these differences were no longer significant. No
      interactions were identified with eptifibatide assignment for any of the group
      comparisons. CONCLUSIONS: Pretreatment with a loading dose of thienopyridine
      lowers the rate of ischemic complications regardless of treatment with a GP
      IIb/IIIa inhibitor. Conversely, the efficacy of eptifibatide is maintained
      whether or not a loading dose of a thienopyridine is administered. Optimal
      outcomes are achieved in patients receiving thienopyridine pretreatment along
      with platelet GP IIb/IIIa inhibitor therapy.

PMID- 17203470
TI  - Interruption of blood flow during compression and radial artery occlusion after
      transradial catheterization.
AB  - OBJECTIVES: To analyze the possible relationship between compression after
      transradial catheterization and radial artery occlusion. BACKGROUND: Radial
      artery occlusion is an important concern of transradial catheterization.
      Interruption of radial artery flow during compression might influence the rate of
      radial artery occlusion at follow-up. METHODS: A prospective study including 275
      consecutive patients undergoing transradial catheterization was conducted.
      Arterial sheaths were removed immediately after procedures and conventional
      compressive dressings were left in place for 2 hr. The pulse oximeter signal in
      the index finger during ipsilateral ulnar compression was used for the assessment
      of radial artery flow. RESULTS: Radial artery flow was absent in 174 cases (62%)
      immediately after entry-site compression. After 2 hr of conventional hemostasis,
      radial artery flow was absent in 162 cases (58%) before bandage removal. At 7-day
      follow-up, 12 patients (4.4%) had absent pulsations and radial artery flow was
      absent in 29 cases (10.5%). Patients with an occluded radial artery at follow-up
      had significantly smaller arterial diameters at baseline (2.23+/-0.4 mm vs.
      2.40+/-0.5 mm; P=0.032) and more frequently had absent flow during hemostasis
      (90% vs. 54%, P<0.001). Stepwise logistic regression analysis revealed that
      absent flow before compressive bandages removal was the only independent
      predictor of radial artery occlusion at follow-up (OR=6.7; IC 95%: 1.95-22.9;
      P=0.002). CONCLUSIONS: Flow-limiting compression is a frequent finding during
      conventional hemostasis after transradial catheterization. Absence of radial
      artery flow during compression represents a strong predictor of radial artery
      occlusion.

PMID- 17203471
TI  - Skin-derived stem cells transplanted into resorbable guides provide functional
      nerve regeneration after sciatic nerve resection.
AB  - The regeneration in the peripheral nervous system is often incomplete and the
      treatment of severe lesions with nerve tissue loss is primarily aimed at
      recreating nerve continuity. Guide tubes of various types, filled with Schwann
      cells, stem cells, or nerve growth factors are attractive as an alternative
      therapy to nerve grafts. In this study, we evaluated whether skin-derived stem
      cells (SDSCs) can improve peripheral nerve regeneration after transplantation
      into nerve guides. We compared peripheral nerve regeneration in adult rats with
      sciatic nerve gaps of 16 mm after autologous transplantation of GFP-labeled SDSCs
      into two different types of guides: a synthetic guide, obtained by dip coating
      with a L-lactide and trimethylene carbonate (PLA-TMC) copolymer and a collagen
      based guide. The sciatic function index and the recovery rates of the compound
      muscle action potential were significantly higher in the animals that received
      SDSCs transplantation, in particular, into the collagen guide, compared to the
      control guides filled only with PBS. For these guides the morphological and
      immunohistochemical analysis demonstrated an increased number of myelinated axons
      expressing S100 and Neurofilament 70, suggesting the presence of regenerating
      nerve fibers along the gap. GFP positive cells were found around regenerating
      nerve fibers and few of them were positive for the expression of glial markers as
      S-100 and glial fibrillary acidic protein. RT-PCR analysis confirmed the
      expression of S100 and myelin basic protein in the animals treated with the
      collagen guide filled with SDSCs. These data support the hypothesis that SDSCs
      could represent a tool for future cell therapy applications in peripheral nerve
      regeneration.

PMID- 17203472
TI  - Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration.
AB  - Inflammation is implicated in the progressive nature of neurodegenerative
      diseases, such as Parkinson's disease, but the mechanisms are poorly understood.
      A single systemic lipopolysaccharide (LPS, 5 mg/kg, i.p.) or tumor necrosis
      factor alpha (TNFalpha, 0.25 mg/kg, i.p.) injection was administered in adult
      wild-type mice and in mice lacking TNFalpha receptors (TNF R1/R2(-/-)) to discern
      the mechanisms of inflammation transfer from the periphery to the brain and the
      neurodegenerative consequences. Systemic LPS administration resulted in rapid
      brain TNFalpha increase that remained elevated for 10 months, while peripheral
      TNFalpha (serum and liver) had subsided by 9 h (serum) and 1 week (liver).
      Systemic TNFalpha and LPS administration activated microglia and increased
      expression of brain pro-inflammatory factors (i.e., TNFalpha, MCP-1, IL-1beta,
      and NF-kappaB p65) in wild-type mice, but not in TNF R1/R2(-/-) mice. Further,
      LPS reduced the number of tyrosine hydroxylase-immunoreactive neurons in the
      substantia nigra (SN) by 23% at 7-months post-treatment, which progressed to 47%
      at 10 months. Together, these data demonstrate that through TNFalpha, peripheral
      inflammation in adult animals can: (1) activate brain microglia to produce
      chronically elevated pro-inflammatory factors; (2) induce delayed and progressive
      loss of DA neurons in the SN. These findings provide valuable insight into the
      potential pathogenesis and self-propelling nature of Parkinson's disease.

PMID- 17203473
TI  - Microglia derived from aging mice exhibit an altered inflammatory profile.
AB  - Microglia play a critical role in neurodegenerative diseases and in the brain
      aging process. Yet, little is known about the functional dynamics of microglia
      during aging. Thus, using young and aging transgenic mice expressing enhanced
      green fluorescent protein (EGFP) under the promoter of the c-fms gene for
      macrophage-colony stimulating factor receptor, we evaluated in vivo-induced
      inflammatory responses of EGFP-expressing microglia sorted by flow cytometry.
      Aging microglia were characterized by the presence of lipofuscin granules,
      decreased processes complexity, altered granularity, and increased mRNA
      expression of both pro-inflammatory (TNFalpha, IL-1beta, IL-6) and anti
      inflammatory (IL-10, TGFbeta1) cytokines. Following lipopolysaccharide (LPS)
      challenge (1 mg/kg, 3 h), aging microglia exhibit increased basal expression of
      TNFalpha, IL-1beta, IL-6, and IL-10. Yet, the fold-over-basal LPS response
      remained constant across age, implying that the inflammatory machinery in aging
      microglia is functional and adjusted to the basal state. Gender differences were
      not overall observed across the treatments (age, LPS). The low but sustained
      production of pro-inflammatory cytokines by aging microglia may have a profound
      impact in the brain aging process.

PMID- 17203474
TI  - Depletion of neutrophils reduces neuronal degeneration and inflammatory responses
      induced by quinolinic acid in vivo.
AB  - The use of anti-neutrophil serum (anti-PMN) to induce neutropenia has been
      assessed for neuroprotection, modulation of microgliosis and astrogliosis,
      effects on oxidative stress, and intactness of blood-brain barrier (BBB)
      following injection of the excitotoxin quinolinic acid (QUIN) into rat striatum.
      At 1 day following QUIN injection, considerable striatal neurodegeneration was
      measured (Fluoro-Jade B marker). At this time, marked microgliosis (OX-42 marker)
      and astrogliosis (GFAP marker) were evident in QUIN-injected striatum. Treatment
      of QUIN-injected animals with anti-PMN protected neurons (48% reduction of
      striatal neuron loss) and inhibited microgliosis (61% reduction) and astrogliosis
      (43% reduction) compared with QUIN injection alone. Anti-PMN treatment was
      effective in decreasing levels of superoxide anions (by 42%) compared with QUIN
      alone; in addition, expressions of the neutrophil enzyme myeloperoxidase and the
      neutrophil oxidant 3-chlorotyrosine were markedly reduced (by 79 and 72%,
      respectively) with neutrophil depletion. QUIN-induced leakiness in BBB was
      indicated by elevated striatal levels of the blood protein fibrinogen, a result
      confirmed using Evans blue dye; anti-PMN was effective in reducing BBB
      permeability. Measurements from QUIN-injected animals directly confirmed anti-PMN
      efficacy in diminishing numbers of circulating neutrophils. Longer term
      neuroprotection and reduced microgliosis were also observed at 7 days post
      injection of anti-PMN; at this time, anti-PMN-treated rats also demonstrated an
      improved apomorphine-induced rotational performance. We conclude that anti-PMN
      treatment could serve as a novel strategy to prevent leakiness to BBB, reduce
      gliosis, and protect striatal neurons in excitotoxin-injected brain.

PMID- 17203475
TI  - Proinflammatory mediators released by activated microglia induces neuronal death
      in Japanese encephalitis.
AB  - While a number of studies have documented the importance of microglia in central
      nervous system (CNS) response to injury, infection and disease, little is known
      regarding its role in viral encephalitis. We therefore, exploited an experimental
      model of Japanese Encephalitis, to better understand the role played by microglia
      in Japanese Encephalitis Virus (JEV) infection. Lectin staining performed to
      assess microglial activation indicated a robust increase in reactive microglia
      following infection. A difference in the topographic distribution of activated,
      resting, and phagocytic microglia was also observed. The levels of various
      proinflammatory mediators, such as inducible nitric oxide synthase (iNOS),
      cyclooxygenase-2 (Cox-2), IL-6, IL-1beta, TNF-alpha, and MCP-1 that have been
      implicated in microglial response to an activational state was significantly
      elevated following infection. These cytokines exhibited region selective
      expression in the brains of infected animals, with the highest expression
      observed in the hippocampus. Moreover, the expression of neuronal specific
      nuclear protein NeuN was markedly downregulated during progressive infection
      indicating neuronal loss. In vitro studies further confirmed that microglial
      activation and subsequent release of various proinflammatory mediators induces
      neuronal death following JEV infection. Although initiation of immune responses
      by microglial cells is an important protective mechanism in the CNS, unrestrained
      inflammatory responses may result in irreparable brain damage. Our findings
      suggest that the increased microglial activation following JEV infection
      influences the outcome of viral pathogenesis. It is likely that the increased
      microglial activation triggers bystander damage, as the animals eventually
      succumb to infection.

PMID- 17203476
TI  - Astroglia-mediated effects of uric acid to protect spinal cord neurons from
      glutamate toxicity.
AB  - Uric acid (UA) has been demonstrated to reduce damage to neurons elicited by
      oxidative stress. However, our studies utilizing cultures derived from embryonic
      rat spinal cord indicate that an astroglia-mediated mechanism is involved in the
      effects of UA to protect neurons from glutamate toxicity. The damage elicted by
      glutamate to neurons in a mixed culture of spinal cord cells can be reversed by
      UA. Furthermore, addition of UA after the termination of glutamate exposure
      suggests that UA plays an active role in mediating neuroprotection rather than
      purely binding peroxynitrite, as previously thought. Importantly, in pure neuron
      cultures from the same tissue, UA does not protect against glutamate toxicity.
      Addition of astroglia to the pure neuron cultures restores the ability of UA to
      protect the neurons from glutamate-induced toxicity. Our results also suggest
      that glia provide EAAT-1 and EAAT-2 glutamate transporters to protect neurons
      from glutamate, that functional EAATs may be necessary to mediate the effects of
      UA, and that treatment with UA results in upregulation of EAAT-1 protein. Taken
      together, our data strongly suggest that astroglia in mixed cultures are
      essential for mediating the effects of UA, revealing a novel mechanism by which
      UA, a naturally produced substance in the body, may act to protect neurons from
      damage during insults such as spinal cord injury.

PMID- 17203477
TI  - A method for detecting the effect of magnetic field on activity changes of
      neuronal populations of Morimus funereus (Coleoptera, Cerambycidae).
AB  - Modification of a new method for detecting changes in the activities of neuronal
      population and the nearest neuron is described. Preliminary measurements of the
      influence of a static magnetic field (2 mT) on neuronal population activity on
      eight individuals of an endangered insect species Morimus funereus are included.
      Five minutes exposure produced both excitatory (5/8) and inhibitory (3/8) effect
      on the activity of neuronal population of M. funereus antennal lobe. However,
      when the reversibility of induced effects was quantitatively analyzed, our
      results showed that they were prevailingly irreversible: (7/8) for the
      population, (6/8) for the nearest neuron.

PMID- 17203478
TI  - Effects of pulsed and continuous wave 902 MHz mobile phone exposure on brain
      oscillatory activity during cognitive processing.
AB  - The aim of the current double-blind studies was to partially replicate the
      studies by Krause et al. [2000ab, 2004] and to further investigate the possible
      effects of electromagnetic fields (EMF) emitted by mobile phones (MP) on the
      event-related desynchronisation/synchronisation (ERD/ERS) EEG
      (electroencephalogram) responses during cognitive processing. Two groups, both
      consisting of 36 male participants, were recruited. One group performed an
      auditory memory task and the other performed a visual working memory task in six
      exposure conditions: SHAM (no EMF), CW (continuous wave EMF) and PM (pulse
      modulated EMF) during both left- and right-side exposure, while the EEG was
      recorded. In line with our previous studies, we observed that the exposure to EMF
      had modest effects on brain oscillatory responses in the alpha frequency range (
      approximately 8-12 Hz) and had no effects on the behavioural measures. The
      effects on the EEG were, however, varying, unsystematic and inconsistent with
      previous reports. We conclude that the effects of EMF on brain oscillatory
      responses may be subtle, variable and difficult to replicate for unknown reasons.

PMID- 17203479
TI  - Complex permittivity of sodium chloride solutions at microwave frequencies.
AB  - The complex permittivity of aqueous solutions at 20 degrees C has been measured
      at concentrations between 0.001 and 5 mol/L and over a frequency range 0.13-20
      GHz. The results were combined with literature values to derive empirical
      equations to predict the dielectric behavior of sodium chloride solutions between
      0 and 5 mol/L and 5 degrees C-35 degrees C.

PMID- 17203480
TI  - Identification and characterization of GFAPkappa, a novel glial fibrillary acidic
      protein isoform.
AB  - Glial fibrillary acidic protein (GFAP) is the principal component of the
      intermediary filaments in mature astrocytes of the central nervous system (CNS).
      The protein consists of three domains: the head, the coiled-coil, and the tail.
      Here, we describe the isolation of an evolutionary conserved novel GFAP isoform,
      GFAPkappa, produced by alternative splicing and polyadenylation of the 3'-region
      of the human GFAP pre-mRNA. As a consequence, the resulting human GFAPkappa
      protein harbors a nonconserved C-terminal tail sequence distinct from the tails
      of GFAPalpha, the predominant GFAP isoform, and GFAPepsilon, an isoform which
      also results from alternative splicing. The head and coiled-coil rod domains are
      identical between the three GFAP isoforms. Interestingly, GFAPkappa is incapable
      of forming homomeric filaments, and increasing GFAPkappa expression levels causes
      a collapse of intermediate filaments formed by GFAPalpha. In searching for a
      biological relevance of GFAPkappa, we noticed that mRNA expression levels of
      GFAPalpha, GFAPepsilon, and GFAPkappa are gradually increased during development
      of the embryonic pig brain. However, whereas the GFAPalpha/GFAPepsilon ratio is
      constant, the GFAPkappa/GFAPepsilon ratio decreases during brain development.
      Furthermore, in glioblastoma tumors, an increased GFAPkappa/GFAPepsilon ratio is
      detected. Our results suggest that the relative expression level of the GFAPkappa
      isoform could modulate the properties of GFAP intermediate filaments and perhaps
      thereby influencing the motility of GFAP positive astrocytes and progenitor cells
      within the CNS.

PMID- 17203481
TI  - Pulsed and continuous wave mobile phone exposure over left versus right
      hemisphere: effects on human cognitive function.
AB  - The possible effects of continuous wave (CW) and pulse modulated (PM)
      electromagnetic field (EMF) on human cognition was studied in 36 healthy male
      subjects. They performed cognitive tasks while exposed to CW, PM, and sham EMF.
      The subjects performed the same tasks twice during each session; once with left
      sided and once with right-sided exposure. The EMF conditions were spread across
      three testing sessions, each session separated by 1 week. The exposed hemisphere,
      EMF condition, and test order were counterbalanced over all subjects. We employed
      a double-blind design: both the subject and the experimenter were unaware of the
      EMF condition. The EMF was created with a signal generator connected via
      amplifier to a dummy phone antenna, creating a power output distribution similar
      to the original commercial mobile phone. The EMF had either a continuous power
      output of 0.25 W (CW) or pulsed power output with a mean of 0.25 W. An additional
      control group of 16 healthy male volunteers performed the same tasks without any
      exposure equipment to see if mere presence of the equipment could have affected
      the subjects' performance. No effects were found between the different EMF
      conditions, separate hemisphere exposures, or between the control and
      experimental group. In conclusion, the current results indicate that normal
      mobile phones have no discernible effect on human cognitive function as measured
      by behavioral tests.

PMID- 17203482
TI  - Hepatic artery stenosis after liver transplant, managed with percutaneous
      angioplasty and stent placement.
AB  - Hepatic artery stenosis is a recognized vascular complication of orthotopic liver
      transplant that carries significant morbidity and mortality. The authors present
      a case of hepatic artery stenosis in a 50-year-old female successfully treated
      with balloon angioplasty and stent. This case report highlights the importance of
      percutaneous intervention as a preferred treatment option in patients with
      hepatic artery stenosis post-orthotopic liver transplant.

PMID- 17203483
TI  - Translocation of constitutively expressed heat shock protein Hsc70 to synapse
      enriched areas of the cerebral cortex after hyperthermic stress.
AB  - Hsp70 is a multi-gene family composed of stress-inducible members (Hsp70) and
      other members that are constitutively expressed (Hsc70). The heat shock proteins
      Hsp70 and Hsc70 exhibit similar molecular structure and biochemical functions.
      Constitutively expressed Hsc70 is enriched in the mammalian nervous system
      compared with non-neural tissues and present at high levels in neuronal cell
      bodies. After thermal stress, Hsc70 is translocated to synapse-enriched areas of
      the cerebral cortex where it associates with Hsp40 to form a complex that can
      refold denaturated proteins. These results suggest that the heat shock response
      in the nervous system involves not only the synthesis of stress-inducible Hsps
      but also the translocation of constitutively expressed Hsc70 to synapse-enriched
      areas where it could participate in neuroprotective mechanisms that preserved
      synaptic function during times of stress.

PMID- 17203484
TI  - Immunohistochemical and hodological characterization of calbindin-D28k-containing
      neurons in the spinal cord of the turtle, Pseudemys scripta elegans.
AB  - Neurons and fibers containing the calcium-binding protein calbindin-D28k (CB)
      were studied by immunohistochemical techniques in the spinal cord of adult and
      juvenile turtles, Pseudemys scripta elegans. Abundant cell bodies and fibers
      immunoreactive for CB were widely and distinctly 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.
      In the dorsal horn, most CB-containing cells were located in close relation to
      the synaptic fields formed by primary afferents, which were not labeled for CB.
      Double immunohistofluorescence demonstrated distinct cell populations in the
      dorsal horn labeled only for CB or nitric oxide synthase, whereas in the dorsal
      part of the ventral horn colocalization of nitric oxide synthase was found in
      about 6% of the CB-immunoreactive cells in this region. Choline acetyltransferase
      immunohistochemistry revealed that only about 2% of the neurons in the dorsal
      part of the ventral horn colocalized CB, whereas motoneurons were not CB
      immunoreactive. The involvement of CB-containing neurons in ascending spinal
      projections to the thalamus, tegmentum, and reticular formation was demonstrated
      combining the retrograde transport of dextran amines and immunohistochemistry.
      Similar experiments demonstrated supraspinal projections from CB-containing cells
      mainly located in the reticular formation but also in the thalamus and the
      vestibular nucleus. The revealed organization of the neurons and fibers
      containing CB in the spinal cord of the turtle shares distribution and
      developmental features, colocalization with other neuronal markers, and
      connectivity with other tetrapods and, in particular with mammals.

PMID- 17203485
TI  - Methods for additive hydration allowing observation of fully hydrated state of
      wet samples in environmental SEM.
AB  - Methods for additive hydration are presented that enable longtime observation of
      very wet biological specimens in an environmental scanning electron microscope.
      The changes of structure due to dehydration for specimens placed on a Peltier
      cooled holder, put on a special agar base or embedded in it or blown over by
      water vapor are compared. The degree of dehydration damage of the observed
      specimen structures is evaluated and compared with the structure of a
      nondestructively dried specimen, prepared by the critical point drying method.

PMID- 17203486
TI  - Karyotypic changes detected by comparative genomic hybridization in a stillborn
      infant with chorioangioma and liver hemangioma.
AB  - BACKGROUND: Placental hemangioma (chorioangioma) and congenital hemangioma are
      relatively common tumors, which on rare occasions may occur together. Very little
      is known about the pathogenetic mechanisms underlying these lesions. CASE: Herein
      we describe a rare case of a stillborn infant with chorioangioma, placental
      mesenchymal dysplasia, and liver cavernous hemangioma. In addition, we present
      the findings of the karyotype analysis of these lesions, which was done with the
      bacterial artificial chromosome arrays using the comparative genomic
      hybridization method. The chromosomal abnormalities that we found were deletions
      at 2q13 and 7p21.1 and were common to both placental and liver lesions.
      CONCLUSIONS: None of the identified chromosomal aberrations have been previously
      associated with chorioangiomas or hemangiomas. Important genes that lie in these
      DNA regions may be implicated in the pathogenesis of congenital hemangiomas and
      mesenchymal dysplasia.

PMID- 17203487
TI  - Retinoic acid and nerve growth factor induce differential regulation of nicotinic
      acetylcholine receptor subunit expression in SN56 cells.
AB  - Retinoic acid (RA) and nerve growth factor (NGF) have multiple functions in the
      regulation of neuronal development. In the present study, we characterized the
      expression of different nicotinic acetylcholine receptor (nAChR) subtypes in the
      cholinergic SN56 cell line and investigated the roles of RA and NGF in the
      expression of choline acetyltransferase (ChAT) and different nAChR subtypes. The
      nAChR agonist [(3)H]epibatidine was bound to two sites, with apparent affinities
      of 13 and 380 pM. RT-PCR analysis revealed expression of alpha3, alpha4, alpha5,
      alpha7, beta2, and beta4 nAChR subunits. RA treatment induced morphological
      changes, and the mRNA level of ChAT was maximally elevated after 4 days of
      exposure. The density of [(3)H]epibatidine binding sites and the mRNA and protein
      level of the alpha3 and beta2 nAChR subunits were also increased by RA-induced
      differentiation. RA down-regulated the mRNA and protein level of the alpha4 nAChR
      subunit, whereas no significant change was observed in the mRNA and protein level
      of the alpha7 nAChR subunit. NGF treatment increased the mRNA and protein level
      of the alpha3 and beta2 nAChR subunits. No morphological effects of NGF were
      observed, and the mRNA level of ChAT and mRNA and protein level of the alpha4 and
      alpha7 nAChR subunits were not significantly altered. Validation was performed
      with real-time RT-PCR. The present results show that RA and NGF have different
      effects on the expression of ChAT and the morphology and the expression pattern
      of different nAChR subunits in cholinergic SN56 cells.

PMID- 17203488
TI  - Alterations in prodynorphin, proenkephalin, and GAD67 mRNA levels in the aged
      human putamen: correlation with Parkinson's disease.
AB  - A real-time quantitative PCR approach was used to quantify mRNA levels
      corresponding to the neuropeptides enkephalin, dynorphin, and the 67-kDa isoform
      of glutamic acid decarboxylase (GAD67) in the human putamen from young and aged
      individuals as well as from aged patients affected by Parkinson's disease (PD).
      cDNA-specific primers were designed to amplify GAD67, proenkephalin (pENK),
      prodynorphin (pDYN), and the housekeeping genes glyceraldehydes-3-phosphate
      dehydrogenase (GAPDH) and guanine nucleotide binding protein, beta-peptide 2-like
      I (GNB2LI). GAPDH and GNB2LI mRNA levels were similarly expressed among the
      groups and were therefore used as endogenous reference genes. Normalized data
      showed that mRNA levels for both pENK and pDYN were reduced in the putamen of
      aged controls and aged individuals affected by PD, compared with young controls.
      In addition, we showed that GAD67 mRNA levels did not change during aging and PD.
      Further analyses showed no differences in mRNA levels, for pENK, pDYN, or GAD67
      mRNA, between PD patients and aged matched controls. These findings contrast with
      animal models of parkinsonism, for which expression of pDYN, pENK, and GAD67 mRNA
      has been reported to change after striatal dopamine denervation. Compensatory
      mechanisms and regional differences within the human putamen as well as the
      severity index of the disease, clinical diagnosis, and response to
      phalmacological therapy are possible reasons for these results. The present study
      suggests that alteration of neuropeptide pathways in the human putamen may be
      involved in the functional deterioration of parts of the extrapyramidal system
      during aging.

PMID- 17203489
TI  - Transplantation of immortalized mesencephalic progenitors (CSM14.1 cells) into
      the neonatal parkinsonian rat caudate putamen.
AB  - The present study analyzed whether grafts of the mesencephalic progenitor cell
      line CSM14.1 into the neonatal rat caudate putamen (CPu) differentiate into
      neurons and whether this is accompanied by a functional improvement in 6
      hydroxydopamine (6-OHDA)-lesioned animals. As in previous studies, a neuronal
      differentiation of CSM14.1 cells transplanted into the CPu of adult animals could
      not be observed, so we here used neonatal rats, because graft location and host
      age seemingly are crucial parameters for neural transplant differentiation and
      integration. Rats bilaterally lesioned at postnatal day 1 by intraventricular 6
      OHDA-injections 2 days later received 100,000 CSM14.1 cells prelabelled with the
      fluorescent dye PKH26 into the right CPu. Five weeks after grafting, the cylinder
      test was performed, and the data compared with data from age-matched intact
      controls and bilaterally lesioned-only animals. Brain slices immunostained for
      tyrosine hydroxylase (TH) were quantified by optical densitometry. We observed a
      significant preference of left forelimb use exclusively in transplanted animals.
      In these rats, TH-containing perikarya were found in the grafted CPu, presumedly
      leading to the significant increase of TH-immunoreactive fibers in this region.
      Moreover, confocal laser microscopy revealed a differentiation of transplanted
      PKH26-labelled CSM14.1 cells into neuronal nuclei antigen or TH-immunoreactive
      cells. Thus, CSM14.1 cells differentiate into TH-containing neurons, which most
      probably contribute to the preferred forelimb use, indicating a functional
      integration of CSM14.1 cells into the host basal ganglia loops during early
      postnatal development. These findings that are in contrast to observations in
      adult rats suggest instructive cues for neuronal differentiation and integration
      given by the neonatal microenvironment.

PMID- 17203491
TI  - Efficient trapping of oxonium ylides with imines: a highly diastereoselective
      three-component reaction for the synthesis of beta-amino-alpha-hydroxyesters with
      quaternary stereocenters.

PMID- 17203492
TI  - Photocontrol of the collagen triple helix: synthesis and conformational
      characterization of bis-cysteinyl collagenous peptides with an azobenzene clamp.
AB  - For the photomodulation of the collagen triple helix with an azobenzene clamp, we
      investigated various collagenous peptides consisting of ideal (Gly-Pro-Hyp)
      repeats and containing cysteine residues in various positions for a side chain-to
      side chain crosslink with a suitable chromophore derivative. Comparative
      conformational analysis of these cysteine peptides indicated an undecarepeat
      peptide with two cysteine residues located in the central portion in i and i+7
      positions and flanked by (Gly-Pro-Hyp) repeat sequences as the most promising for
      the cross-bridging experiments. In aqueous alcoholic solution the azobenzene
      undecarepeat peptide formed a stable triple helix in equilibrium with the
      monomeric species as a trans-azobenzene isomer, whereas photoisomerization to the
      cis isomer leads to unfolding of at least part of the triple helix. Furthermore,
      the residual supercoiled structure acts like an intermolecular knot, thus making
      refolding upon cis-to-trans isomerization a concentration-independent fast event.
      Consequently, these photoswitchable collagenous systems should be well suited for
      time-resolved studies of folding/unfolding of the collagen triple helix under
      variable thermodynamic equilibria.

PMID- 17203493
TI  - 1,3-bicyclo[1.1.1]pentanediyl: the shortest rigid linear connector of phenylated
      photochromic units and a 1,5-dimethoxy-9,10-di(phenylethynyl)anthracene
      fluorophore.
AB  - An excess of bis-1,3-(4-iodophenyl)bicyclo[1.1.1]pentane, prepared in 63 % yield
      by iodination of 1,3-diphenylbicyclo[1.1.1]pentane, was selectively mono-coupled
      with 9-ethynyl-1,5-dimethoxy-10-phenylethynylanthracene (26), and subsequently
      with the zinc derivatives of 1-(2-methyl/methoxy-4-methyl-5-phenylthiophen-3-yl)
      2-(2-methyl/methoxy-4-methylthiophen-3-yl)perfluorocyclopentenes (38-H-41-H).
      Regioselective synthesis of the 2-unsubstituted thiophenes 38-H-41-H required
      intermediate preparation of 2-trimethylsilyl-3,5-dimethyl-4-bromothiophene (37)
      or 2-trimethylsilyl-5-methoxy-3-methyl-4-bromothiophene (40). Protection of the
      alpha-position of the thiophene ring with a 2-trimethylsilyl group blocks the
      rearrangement of the 4-lithio derivatives into the corresponding 2-lithiated
      thiophenes. With the bicyclo[1.1.1]pentane fragment linking the photochromic
      units 1-3 and 1,5-dimethoxy-9,10-di(phenylethynyl)anthracene as a fluorescent
      part, quantitative resonance energy transfer between the excited state of the
      fluorophore (donor) and the closed form of the photochromic units 1-3 (acceptors)
      was observed. The closed forms of the methoxy-substituted photochromic units 2
      and 3 are less resistant to UV light (313 nm) than the closed form of 1.

PMID- 17203494
TI  - A general strategy for the rational design of size-selective mesoporous
      catalysts.
AB  - A series of functionalized mesoporous silicas with cagelike pore topology has
      been synthesized and screened for size-selective catalytic transformations. The
      aluminum-catalyzed Meerwein-Ponndorf-Verley (MPV) reduction of differently sized
      aromatic aldehydes (benzaldehyde and 1-pyrenecarbox-aldehyde) has been
      investigated as a test reaction. The catalysts were synthesized in a two-step
      grafting sequence comprising pore-size engineering of mesoporous silicas (SBA-1,
      SBA-2, SBA-16) with long-chain alkyl dimethylaminosilanes and surface
      organoaluminum chemistry with triethylaluminum [{Al(CH(2)CH(3))3}2]. Size
      selective reaction behavior was found for small pore SBA-1 materials, and the
      selectivity could be efficiently tuned by selecting a silylating reagent of
      appropriate size. The results are compared with the catalytic performance of a
      large-pore periodic mesoporous organosilica PMO[SBA-1] and the nonporous high
      surface-area silicas Aerosil 300/380.

PMID- 17203495
TI  - Dynamic modulation of chemical concentration in an aqueous droplet.

PMID- 17203496
TI  - In situ high-energy synchrotron radiation study of sol-gel nanoparticle formation
      in supercritical fluids.

PMID- 17203497
TI  - Highly enantioselective hydrosilylation/cyclization of 1,6-enynes catalyzed by
      rhodium(I) complexes of spiro diphosphines.

PMID- 17203498
TI  - IAPP mimic blocks Abeta cytotoxic self-assembly: cross-suppression of amyloid
      toxicity of Abeta and IAPP suggests a molecular link between Alzheimer's disease
      and type II diabetes.

PMID- 17203499
TI  - Zeolite shape-selectivity in the gem-methylation of aromatic hydrocarbons.

PMID- 17203500
TI  - Artificial zinc(II) complexes regulate cell cycle and apoptosis-related genes in
      tumor cell lines.
AB  - Various proteins involved in transcriptional regulation possess highly selective
      DNA-binding domains, known as zinc fingers. However, little is known about small
      molecule zinc(II) complexes in the regulation of gene expression and programmed
      cell death. A new family of zinc(II) complexes is reported, which might be useful
      against human cancer cells. By using template synthesis and in vitro cell-line
      screening, a set of zinc(II) complexes has been found to induce apoptosis of
      cancer cells and display single-reagent in vitro cytotoxicity. The method used to
      synthesize the molecules resulted in "built-in" luminescent behavior. Confocal
      optical imaging clearly demonstrated penetration through the cell membrane by
      these metal complexes. We have discovered that C3, the meso-zinc(II) complex is
      an extremely efficient regulator of the cell cycle and anti-apoptosis genes bcl-2
      and bcl-xL. This study provides a new insight into the development of zinc(II)
      complexes as potential drugs.

PMID- 17203501
TI  - Involvement of alanine 103 residue in kinetic and physicochemical properties of
      glucose isomerases from Streptomyces species.
AB  - The Ala103 to Gly mutation, introduced within the glucose isomerase from
      Streptomyces sp. SK (SKGI) decreased its catalytic efficiency (k(cat)/K(m))
      toward D-glucose from 7.1 to 3 mM(-1) min(-1). The reverse counterpart
      replacement Gly103Ala introduced into the glucose isomerase of Streptomyces
      olivochromogenes (SOGI) considerably improved its catalytic efficiency to be 6.7
      instead of 3.2 mM(-1) min(-1). This later mutation also increased the half-life
      time of the enzyme from 70 to 95 min at 80 degrees C and mainly modified its pH
      profile. These results provide evidence that the residue Ala103 plays an
      essential role in the kinetic and physicochemical properties of glucose
      isomerases from Streptomyces species.

PMID- 17203502
TI  - Volsurf computational method applied to the prediction of stability of
      thermostable enzymes.
AB  - A computational model for the quantitative prediction of protein thermostability
      has been developed by means of the Volsurf method. A data set of 22 enzymes of
      reported thermostability in water systems, for the most part coming from
      thermophilic and hyperthermophilic organisms, has been built up. Molecular
      descriptors of the protein surface have been calculated and their role in the
      stabilization of the macromolecule has been analyzed by a multivariate
      statistical approach. The resulting regression model has shown a good
      predictivity and it has been able to quantitatively identify some structural
      requirements correlated with protein stability. The method can be the basis for a
      new computational support tool in rational protein design, which is complementary
      to the existing methods based on the sequence analysis.

PMID- 17203505
TI  - Capillary electrophoretic method for nucleotide analysis in cells: application on
      inherited metabolic disorders.
AB  - Purine and pyrimidine nucleotides influence many metabolic pathways and their
      analogs have been widely used in medicine. A capillary electrophoretic method was
      developed for measuring intracellular nucleotides. The final BGE consisted of 40
      mM citric acid with addition of 0.8 mM CTAB titrated by gamma-aminobutyric acid
      to pH 4.4. The electrophoretic separations were carried out in an uncoated silica
      capillary (id/od - 75/375 microm; effective/total length - 90/97 cm). The method
      allows a complete separation of 21 nucleotides and deoxynucleotides within 15 min
      with separation efficiencies up to 400,000 theoretical plates per meter. Due to
      the use of an acidic separation medium, the method offers a high selectivity
      toward the studied analytes versus possible interferences from matrices. Sample
      preparation was optimized in order to shorten work-time and prevent analyte
      degradation. The method was applied for analyzing nucleotides in human
      erythrocytes and Chinese hamster ovary cells. Diagnostic potential for inherited
      metabolic disorders of nucleotide metabolism is presented.

PMID- 17203506
TI  - Full-fledged proteomic analysis of bioactive wheat amylase inhibitors by a 3-D
      analytical technique: Identification of new heterodimeric aggregation states.
AB  - Wheat proteinaceous alpha-amylase inhibitors (alpha-AIs) are increasingly
      investigated for their agronomical role as natural defence molecules of plants
      against the attack of insects and pests, but also for their effects on human
      health. The wheat genomes code for several bioactive alpha-AIs that share
      sequence homology, but differ in their specificity against alpha-amylases from
      different species and for their aggregation states. Wheat alpha-AIs are
      traditionally classified as belonging to the three classes of tetrameric,
      homodimeric and monomeric forms, each class being constituted by a number of
      polypeptides that display different electrophoretic mobilities. Here we describe
      a proteomic approach for the identification of bioactive alpha-AIs from wheat
      and, in particular, a 3-D technique that allows to best identify and characterize
      the dimeric fraction. The technique takes advantage of the thermal resistance of
      alpha-AIs (resistant to T > 70 degrees C) and consists in the separation of
      protein mixtures by 2-D polyacrylamide/starch electrophoresis under
      nondissociating PAGE (ND-PAGE, first dimension) and dissociating (urea-PAGE or U
      PAGE second dimension) conditions, followed by in-gel spontaneous reaggregation
      of protein complexes and identification of the alpha-amylase inhibitory activity
      (antizymogram, third dimension) using enzymes from human salivary glands and from
      the larvae of Tenebrio molitor coleopter (yellow mealworm). Dimeric alpha-AIs
      from Triticum aestivum (bread wheat) were observed to exist as heterodimers. The
      formation of heterodimeric complexes was also confirmed by in vitro reaggregation
      assays carried out on RP-HPLC purified wheat dimeric alpha-AIs, and their
      bioactivity assayed by antizymogram analysis. The present 3-D analytical
      technique can be exploited for fast, full-fledged identification and
      characterization of wheat alpha-AIs.

PMID- 17203507
TI  - Simultaneous detection of molecular weight and activity of adenylate kinases
      after electrophoretic separation.
AB  - Adenylate kinases (AKs) are ubiquitous monomeric phosphotransferases catalyzing
      the reversible reaction, AMP + MgATP = ADP + MgADP, which plays a pivotal role in
      the energetic metabolism. In vertebrates, six AK isoforms are known. In this
      work, we report the detection of many AK isoforms directly on gel or NC after
      separation by denaturing electrophoresis and electroblotting, by an optimized
      protocol for the enzyme detection. The method allows to clarify the apparent MW
      of most of those AK isozymes that follow the cited reaction, especially onto NC
      where bands are sharper due to the absence of protein diffusion. In contrast,
      GTP:AMP phosphotransferases are not detectable. AK activity from many sources can
      be detected in both its reaction courses; ATP production appears as dark-blue
      bands, while ADP formation appears as nonfluorescent bands over a fluorescent
      background, under long-wavelength UV light. We show that nondenaturing gel
      electrophoresis is not the first choice for AK activity detection. Our method is
      different from the preceding reports on AK activity detection in bacteria after
      native polyacrylamide gel separations, in the absence of SDS or methanol. The
      procedure is also quantitative, allowing to determine the amount of enzyme
      present in samples.

PMID- 17203508
TI  - CE frontal analysis based on simultaneous UV and contactless conductivity
      detection: a general setup for studying noncovalent interactions.
AB  - CE frontal analysis (CE-FA) has been established as a powerful tool to study
      noncovalent interactions between macromolecules and small molecules such as drug
      substances or pharmaceutical excipients. However, when using traditional
      commercial CE instrumentation, a serious drawback is related to the fact that
      only UV-active compounds can be studied. In recent years, contactless
      conductivity detection has become an attractive alternative to UV detection in CE
      due to its high versatility. In this study, we combine contactless conductivity
      detection and UV detection in a highly versatile setup for profiling noncovalent
      interactions between low-molecular-weight molecules and macromolecules. In the
      case of molecules having a chromophore the setup allows determination of binding
      constants using two independent detectors. The new contactless conductivity
      detection cell is compatible with commercial CE instrumentation and is therefore
      easily implemented in any analysis laboratory with CE expertise.

PMID- 17203509
TI  - Characterization of extracellular proteins produced by Aeromonas hydrophila AH-1.
AB  - Aeromonas hydrophila is a ubiquitous Gram-negative bacterium which can cause
      motile aeromonad septicemia in both fish and humans. A. hydrophila secretes many
      extracellular proteins associated with pathogenicity and environmental
      adaptability. In this study, an extracellular proteome map of A. hydrophila AH-1
      was constructed. The major extracellular virulence factors were characterized by
      comparing the proteomes of various deletion mutants with that of the wild type.
      The results suggested that serine protease was involved in the processing of a
      toxin and secreted enzymes such as hemolysin, glycerophospholipid-cholesterol
      acyltransferase and metalloprotease. We also showed that expressions of polar and
      lateral flagellins were under the control of temperature, FlhA, LafK, and RpoN.
      In addition, three novel proteins (potential effector proteins including one ExoT
      like protein) were revealed to be secreted via the type III secretion system
      (TTSS) of A. hydrophila AH-1. Another novel finding was the demonstration of a
      crosstalk between the lateral flagellar system and the TTSS in A. hydrophila.
      These results showed that proteomics is a powerful tool for characterizing
      virulence factors. The construction of proteome maps will provide a valuable
      means of finding potential candidates for developing suitable diagnostics and
      therapeutics for this emerging pathogen.

PMID- 17203510
TI  - MascotDatfile: an open-source library to fully parse and analyse MASCOT MS/MS
      search results.
AB  - MS-based protein identification is an important part of both gel-based and gel
      free proteome studies. The MASCOT search engine (http://www.matrixscience.com)
      provides one of the most popular automated algorithms for this task. Here we
      present an open-source software library written in Java that parses raw MASCOT
      results into an easily accessible and fully functional object model
      (http://genesis.ugent.be/MascotDatfile). Several scripts based on this library
      are provided as examples, allowing direct automation of important routine tasks
      involved in processing peptide identifications.

PMID- 17203511
TI  - APOE and cytokines as biological markers for recovery of prevalent delirium in
      elderly medical inpatients.
AB  - BACKGROUND: Delirium frequently occurs in the context of infection and other
      inflammatory conditions associated with elevated levels of cytokines. Cytokines
      used therapeutically can induce symptoms of delirium as an adverse effect. We
      hypothesized that a causal relationship might exist between delirium and cytokine
      production during illness. Further, we speculated that the APOE genotype of
      patients might influence their rate of recovery from delirium given that APOE is
      associated with amyloid deposition, increased susceptibility to exogenous
      neurotoxins, and can affect the immune response. METHODS: A cohort of 164 acutely
      ill patients, 70 years or older, admitted to an elderly medical unit were studied
      within 3 days of hospital admission and re-assessed twice weekly until their
      discharge, to identify and follow the clinical course of delirium. The APOE
      genotype and the level of circulating cytokines were determined for 116 and 60
      patients respectively. RESULTS: Prevalent delirium was significantly (p < 0.05)
      associated with a previous history of dementia, age, illness severity, disability
      and low levels of circulating IGF-I. Recovery was significantly associated (p <
      0.05) with lack of APOE 4 allele and higher initial IFN-gamma. A model
      incorporating gender, APOE epsilon 4 status and IGF-I levels predicted recovery
      or not from delirium in 76.5% of cases, with a sensitivity 0.77 and specificity
      0.75. CONCLUSIONS: A relationship between delirium with APOE genotype, IFN-gamma,
      and IGF-I, but not with IL-6, IL-1, TNF-alpha, and LIF was found. A predictive
      model of recovery was derived from gender, APOE status, and IGF-I levels. This
      model needs replication with further studies.

PMID- 17203512
TI  - New insights into the coagulopathy of liver disease and liver transplantation.
AB  - The liver is an essential player in the pathway of coagulation in both primary
      and secondary haemostasis. Only von Willebrand factor is not synthetised by the
      liver, thus liver failure is associated with impairment of coagulation. However,
      recently it has been shown that the delicate balance between pro and
      antithrombotic factors synthetised by the liver might be reset to a lower level
      in patients with chronic liver disease. Therefore, these patients might not be
      really anticoagulated in stable condition and bleeding may be caused only when
      additional factors, such as infections, supervene. Portal hypertension plays an
      important role in coagulopathy in liver disease, reducing the number of
      circulating platelets, but platelet function and secretion of thrombopoietin have
      been also shown to be impaired in patients with liver disease. Vitamin K
      deficiency may coexist, so that abnormal clotting factors are produced due to
      lack of gamma carboxylation. Moreover during liver failure, there is a reduced
      capacity to clear activated haemostatic proteins and protein inhibitor complexes
      from the circulation. Usually therapy for coagulation disorders in liver disease
      is needed only during bleeding or before invasive procedures. When end stage
      liver disease occurs, liver transplantation is the only treatment available,
      which can restore normal haemostasis, and correct genetic clotting defects, such
      as haemophilia or factor V Leiden mutation. During liver transplantation
      haemorrage may occur due to the pre-existing hypocoagulable state, the collateral
      circulation caused by portal hypertension and increased fibrinolysis which occurs
      during this surgery.

PMID- 17203513
TI  - Contribution of altered signal transduction associated to glutamate receptors in
      brain to the neurological alterations of hepatic encephalopathy.
AB  - Patients with liver disease may present hepatic encephalopathy (HE), a complex
      neuropsychiatric syndrome covering a wide range of neurological alterations,
      including cognitive and motor disturbances. HE reduces the quality of life of the
      patients and is associated with poor prognosis. In the worse cases HE may lead to
      coma or death. The mechanisms leading to HE which are not well known are being
      studied using animal models. The neurological alterations in HE are a consequence
      of impaired cerebral function mainly due to alterations in neurotransmission. We
      review here some studies indicating that alterations in neurotransmission
      associated to different types of glutamate receptors are responsible for some of
      the cognitive and motor alterations present in HE. These studies show that the
      function of the signal transduction pathway glutamate-nitric oxide-cGMP
      associated to the NMDA type of glutamate receptors is impaired in brain in vivo
      in HE animal models as well as in brain of patients died of HE. Activation of
      NMDA receptors in brain activates this pathway and increases cGMP. In animal
      models of HE this increase in cGMP induced by activation of NMDA receptors is
      reduced, which is responsible for the impairment in learning ability in these
      animal models. Increasing cGMP by pharmacological means restores learning ability
      in rats with HE and may be a new therapeutic approach to improve cognitive
      function in patients with HE. However, it is necessary to previously assess the
      possible secondary effects. Patients with HE may present psychomotor slowing,
      hypokinesia and bradykinesia. Animal models of HE also show hypolocomotion. It
      has been shown in rats with HE that hypolocomotion is due to excessive activation
      of metabotropic glutamate receptors (mGluRs) in substantia nigra pars reticulata.
      Blocking mGluR1 in this brain area normalizes motor activity in the rats,
      suggesting that a similar treatment for patients with HE could be useful to treat
      psychomotor slowing and hypokinesia. However, the possible secondary effects of
      mGluR1 antagonists should be previously evaluated. These studies are setting the
      basis for designing therapeutic procedures to specifically treat the individual
      neurological alterations in patients with HE.

PMID- 17203514
TI  - Food allergy in gastroenterologic diseases: Review of literature.
AB  - Food allergy is a common and increasing problem worldwide. The newly-found
      knowledge might provide novel experimental strategies, especially for laboratory
      diagnosis. Approximately 20% of the population alters their diet for a perceived
      adverse reaction to food, but the application of double-blind placebo-controlled
      oral food challenge, the "gold standard" for diagnosis of food allergy, shows
      that questionnaire-based studies overestimate the prevalence of food allergies.
      The clinical disorders determined by adverse reactions to food can be classified
      on the basis of immunologic or nonimmunologic mechanisms and the organ system or
      systems affected. Diagnosis of food allergy is based on clinical history, skin
      prick tests, and laboratory tests to detect serum-food specific IgE, elimination
      diets and challenges. The primary therapy for food allergy is to avoid the
      responsible food. Antihistamines might partially relieve oral allergy syndrome
      and IgE-mediated skin symptoms, but they do not block systemic reactions.
      Systemic corticosteroids are generally effective in treating chronic IgE-mediated
      disorders. Epinephrine is the mainstay of treatment for anaphylaxis. Experimental
      therapies for IgE-mediated food allergy have been evaluated, such as humanized
      IgG anti-IgE antibodies and allergen specific immunotherapy.

PMID- 17203515
TI  - Mechanisms of regulation and function of G-protein-coupled receptor kinases.
AB  - G-protein-coupled receptor kinases (GRKs) interact with the agonist-activated
      form of G-protein-coupled receptor (GPCR) to affect receptor phosphorylation and
      to initiate profound impairment of receptor signaling, or desensitization. GPCR
      forms the largest family of cell surface receptors, and defects in GRK function
      have the potential consequence to affect GPCR-stimulated biological responses in
      many pathological situations.

PMID- 17203516
TI  - Glutathione-S-transferase M1 polymorphisms on the susceptibility to esophageal
      cancer among three Chinese minorities: Kazakh, Tajik and Uygur.
AB  - AIM: To investigate the glutathione-S-transferase M1 (GSTM1) polymorphisms in
      three Chinese minorities, Kazakh, Uygur, and Tajik; and the pathological
      significance of GSTM1 polymorphisms in esophageal carcinogenesis in Kazakh.
      METHODS: A total of 1121 blood samples (442 males and 679 females) were obtained
      from healthy Kazakh (654), Uygur (412) and Tajik (55). Primary esophageal
      squamous cell cancer (ESCC) tissues from Kazakh were obtained from 116 patients
      who underwent surgery. GSTM1 polymorphisms were analyzed by a combined approach
      of PCR and electrophoresis techniques. RESULTS: GSTM1 null genotype was found in
      62.63% Uygur, 50.91% Tajik and 47.40% Kazakh. A significantly higher frequency of
      GSTM1 null genotype in Uygur was observed compared with Kazakh (OR: 1.859, 95%
      CI: 1.445 -2.391, chi2 = 23.71, P = 0.000). In addition, GSTM1 null genotype was
      found in 23.53% of well-differentiated ESCC in Kazakh, in 49.23% of poorly
      differentiated ESCC, with a significant difference (OR: 3.152, 95% CI: 1.403
      7.080, chi2 = 8.018, P = 0.007). CONCLUSION: There is a marked difference in the
      frequency of common GSTM1 null genotype between Uygur and Kazakh. GSTM1 null
      genotype is associated with differentiation of ESCC in Kazakh.

PMID- 17203517
TI  - Role of the HLA-DQ locus in the development of chronic gastritis and gastric
      carcinoma in Mexican patients.
AB  - AIM: To determine the HLA-DQ locus in Mexican patients with Chronic gastritis and
      gastric adenocarcinoma. METHODS: Oligotyping for HLA-DQ locus was performed in 45
      Mexican patients with chronic gastritis and 13 Mexican patients with diffuse-type
      gastric adenocarcinoma, and was then compared with 99 clinically healthy
      unrelated individuals. H pylori infection and CagA status were assessed in
      patients by enzyme-linked immunosorbent assay (ELISA) method. RESULTS: We found a
      significant increased frequency of HLA-DQB1*0401 allele in H pylori-positive
      patients with chronic gastritis when compared with healthy subjects [19 vs 0%, P
      = 1 x 10(-7), odds ratio (OR) = 4.96; 95% confidence interval (95% CI), 3.87
      6.35]. We also found a significant increased frequency of HLA-DQB1*0501 in
      patients with diffuse-type gastric carcinoma in comparison with healthy
      individuals (P = 1 x 10(-6), OR = 13.07; 95% CI, 2.82-85.14). CONCLUSION: HLA-DQ
      locus may play a different role in the development of H pylori-related chronic
      gastritis and diffuse-type gastric adenocarcinoma in the Mexican Mestizo
      population.

PMID- 17203518
TI  - Usefulness of noninvasive transient elastography for assessment of liver fibrosis
      stage in chronic hepatitis C.
AB  - AIM: To evaluate the method of noninvasive transient elastography for assessment
      of histological stage of liver fibrosis in patients with chronic hepatitis C
      (CHC). METHODS: Two hundred and thirty-seven patients with CHC were included in
      this study. Liver biopsy was performed under ultrasonography on 217 of the
      patients, excluding twenty with clear clinical evidence of liver cirrhosis. Fifty
      subjects without liver disease were enrolled as a control group (stage 0). Twenty
      five patients with sustained virological response (SVR) to interferon (IFN)
      therapy were also enrolled. These patients underwent liver biopsy before IFN
      therapy. Examination of liver stiffness (LS) was performed by elastography.
      RESULTS: Medians (50% levels) of LS were 4.1 (3.5-4.9), 6.3 (4.8-8.5), 8.8 (6.8
      12.0), 14.6 (10.5-18.6), and 22.2 (15.4-28.0), respectively, in the fibrosis
      stages 0-4 (P < 0.001). LS was significantly correlated with four serum fibrosis
      markers. LS values in patients with SVR were 3.8 (3.5-5.6), 5.2 (4.4-6.8), 6.8
      (6.1-7.6), and 6.1 (3.6-7.9), respectively, in the fibrosis stages 1-4. In all
      stages, LS for patients with SVR was significantly lower than that for patients
      who did not undergo IFN therapy. LS was significantly correlated with serum
      concentrations of hyaluronic acid, type IV collagen, type IV collagen 7S, and
      type III procollagen N peptide. CONCLUSION: LS correlated well with the
      histological stage of fibrosis. Changes in liver fibrosis stage may thus be
      estimated noninvasively using transient elastography.

PMID- 17203519
TI  - Development of hepatitis C virus vaccine using hepatitis B core antigen as immuno
      carrier.
AB  - AIM: To develop hepatitis C virus (HCV) vaccine using HBcAg as the immuno-carrier
      to express HCV T epitope and to investigate its immunogenicity in mice. METHODS:
      We constructed the plasmid pTrc-core(NheI) using gene engineering technique,
      constructed the pcDNA3.1-core(NheI)-GFP plasmid with GFP as the reporter gene,
      and transfected them into Hela cells. The expression of GFP was observed under
      confocal microscopy and the feasibility of using HBcAg as an immuno-carrier
      vaccine was studied. pTrc-core gene with a synthetic T epitope antigen gene of
      HCV (35-44aa) was fused and expressed in the plasmid pTrc-core-HCV (T). For the
      fusion of the HBcAg-T protein, sucrose, density gradient centrifugation was used,
      and its molecular weight and purity were analyzed by SDS-PAGE. Then balb/c mice
      were immunized by the plasmid with the HBcAg (expressed by pTrc-core) protein as
      control. The tumor regression potential was investigated in mice and evaluated at
      appropriate time. After three times of immunization, the peripheral blood and
      spleen of vaccinated mice were collected. HBcAb was detected by ELISA, and
      nonspecific T lymphocyte proliferation and response of splenocytes were
      respectively examined by MTT assay. T cell subset of blood and spleen were
      detected by FACS. RESULTS: GFP was successfully expressed. Tumor regression trial
      showed that no tumor formation was found in the group receiving immunization,
      while tumor xenograft progression was not changed in the control group. Strong
      nonspecific lymphocyte proliferation response was induced. FACS also showed that
      the ratio of CD8+ T cells in the experimental group was higher than the controls,
      but the serum HBcAb in experimental group was similar to the control. CONCLUSION:
      HBcAg can be used as an immuno-carrier of vaccine, the fusion of HBcAg-T protein
      could induce stronger cellular immune responses and it might be a candidate for
      therapeutic vaccines specific for HCV.

PMID- 17203520
TI  - Validation of the Rockall scoring system for outcomes from non-variceal upper
      gastrointestinal bleeding in a Canadian setting.
AB  - AIM: To validate the Rockall scoring system for predicting outcomes of
      rebleeding, and the need for a surgical procedure and death. METHODS: We used
      data extracted from the Registry of Upper Gastrointestinal Bleeding and Endoscopy
      including information of 1869 patients with non-variceal upper gastrointestinal
      bleeding treated in Canadian hospitals. Risk scores were calculated and used to
      classify patients based on outcomes. For each outcome, we used chi2 goodness-of
      fit tests to assess the degree of calibration, and built receiver operating
      characteristic curves and calculated the area under the curve (AUC) to evaluate
      the discriminative ability of the scoring system. RESULTS: For rebleeding, the
      chi2 goodness-of-fit test indicated an acceptable fit for the model [chi2 (8) =
      12.83, P = 0.12]. For surgical procedures [chi2 (8) = 5.3, P = 0.73] and death
      [chi2 (8) = 3.78, P = 0.88], the tests showed solid correspondence between
      observed proportions and predicted probabilities. The AUC was 0.59 (95% CI: 0.55
      0.62) for the outcome of rebleeding and 0.60 (95% CI: 0.54-0.67) for surgical
      procedures, representing a poor discriminative ability of the scoring system. For
      the outcome of death, the AUC was 0.73 (95% CI: 0.69-0.78), indicating an
      acceptable discriminative ability. CONCLUSION: The Rockall scoring system
      provides an acceptable tool to predict death, but performs poorly for endpoints
      of rebleeding and surgical procedures.

PMID- 17203521
TI  - Factors influencing health-related quality of life in chronic liver disease.
AB  - AIM: To investigate the factors contributing to health-related quality of life
      (HRQL) in chronic liver disease (CLD). METHODS: Patients with CLD and age- and
      sex-matched normal subjects performed the validated Thai versions of the short
      form 36 (SF-36) by health survey and chronic liver disease questionnaire (CLDQ).
      Stepwise multiple regression analysis was used to assess the impact of disease
      severity, demography, causes of CLD, socioeconomic factors, and self-rating
      health perception on HRQL. RESULTS: Two-hundred and fifty patients with CLD and
      fifty normal subjects were enrolled into the study. Mean age and the numbers of
      low educated, unemployed, blue-collar career and poor health perception increased
      significantly from chronic hepatitis to Child's Classes A to B to C. Advanced
      stage of CLD was related to deterioration of HRQL. Increasing age and female
      reduced physical health area. Low socioeconomic factors and financial burden
      affected multiple areas of HRQL. In overall, the positive impact of self-rating
      health perception on HRQL was consistently showed. CONCLUSION: Advanced stages of
      chronic liver disease, old age, female sex, low socioeconomic status and
      financial burden are important factors reducing HRQL. Good health perception
      improves HRQL regardless of stages of liver disease.

PMID- 17203522
TI  - Disease-specific health-related quality of life and its determinants in liver
      cirrhosis patients in Lithuania.
AB  - AIM: To evaluate disease-specific quality of life (QOL) in liver cirrhosis
      patients and to compare it with those of a healthy population. Also an important
      objective was to assess whether QOL in liver cirrhosis patients differs by age
      and gender, by type and severity of disease. METHODS: The case group of 131 liver
      cirrhosis patients was selected. The control group of 262 was enrolled from a
      healthy population according to the scheme of case-control study. Clinical,
      demographic, laboratory data were collected. QOL was measured with a specific
      chronic liver disease questionnaire (CLDQ), which was translated and validated in
      Lithuanian. QOL scores were compared between groups by age, gender, type and
      severity of disease. Cronbach's alpha statistics calculation was used for
      evaluation of internal consistency reliability. Student's t test or ANOVA were
      used for evaluation hypothesis about probability equation. RESULTS: QOL was
      significantly lower in liver cirrhosis patients than in healthy population (59.5
      +/- 18.3 vs 85.3 +/- 12.3, P < 0.001). The significant QOL differences between
      case and control groups were observed in domains of worry and abdominal symptoms,
      the smaller differences-in emotional functions and systematic symptom domains.
      Significantly worse QOL was in observed patients with increased clinical severity
      of the disease measured by Child-Pugh class. Age, gender and etiology of disease
      had an insignificant effect on QOL in cirrhotic patients. CONCLUSION: QOL was
      significantly impaired in all CLDQ domains in liver cirrhosis patients. Increase
      in severity of disease was the major factor associated with poorer QOL.

PMID- 17203523
TI  - Clinical research on navel application of Shehuang Paste combined with Chinese
      herbal colon dialysis in treatment of refractory cirrhotic ascites complicated
      with azotemia.
AB  - AIM: To explore the efficacy and mechanism of a novel therapeutic method of
      traditional Chinese medicine in patients with refractory cirrhotic ascites
      complicated with azotemia. METHODS: Seventy-five cases of refractory cirrhotic
      ascites complicated with azotemia were randomly divided into 3 groups:
      comprehensive treatment (n = 29), simple treatment (n = 24), and control (n =
      22). The basic treatment methods were the same in all groups, including liver
      protecting medicines, diuretics and supportive drugs. The control group underwent
      only the basic treatment. Shehuang Paste (SHP) was applied to the navels of the
      two treatment groups once a day for 30 d. Colon dialysis with Chinese herbs was
      administered to the comprehensive treatment group once every two days. Before and
      after treatment, we measured abdominal circumference, BUN, Cr, serum Na+, urine
      Na+/K+, liver function, endotoxin content, NO, and ET-1. Color Doppler
      ultrasonography was conducted to measure the portal vein blood flow. RESULTS: The
      total effective rate for ascites was 72.4% in the comprehensive treatment group,
      45.8% in the simple treatment, contrasting with 18.2% in the controls. Between
      the two treatment groups and the controls, there were significant differences in
      the effective rates (P < 0.01, and P < 0.05). There was also a significant
      difference (P < 0.05) between the two treatment groups. Measurements of Cr and
      BUN showed higher values for the treatment groups, with the comprehensive better
      than the simple group (P < 0.05). Sera Na, urine Na/K were different, P < 0.01
      between pre- and post-treatment in the comprehensive group, and P < 0.05 in the
      simple group. The treatment groups' endotoxin content was also significantly
      reduced (P < 0.01, and P < 0.05), with the comprehensive group better than the
      simple group (P < 0.05). Portal vein blood flow and NO content significantly
      reduced (P < 0.05), as did ET-1 content (P < 0.01). There were no significant
      changes in the control group (P > 0.05). The comprehensive treatment group's pre-
      and post-treatment portal vein and splenic vein blood flows showed a positive
      correlation to NO, ET-1 and endotoxin contents. CONCLUSION: When treating
      refractory cirrhotic ascites complicated with azotemia, Shehuang Paste combined
      with Chinese herbal dialysis is better than Shehuang Paste alone for ascites
      resolution, azotemia, and endotoxin elimination. However, both methods on their
      own were also effective for reducing portal and splenic vein blood flow, and
      lowering the contents of NO, ET-1 in the two treatment groups.

PMID- 17203524
TI  - An algorithm for family screening for coeliac disease.
AB  - AIM: To assess the level of undiagnosed coeliac disease (CD) in relatives of
      patients affected by the condition. METHODS: We collected blood from 914
      relatives of probands. We screened these individuals by ELISA for IgA and IgG tTG
      antibodies, confirming any positive IgA tTG results with an IgA EMA and looked
      for evidence of IgA deficiency in those who were IgG tTG positive alone, and
      performed IgG1 EMA in these individuals. We undertook HLA typing where positive
      screening was found, and this confirmed a strong prevalence of HLA-DQ2 in the
      coeliac population. Follow-up small intestinal biopsy was undertaken in cases
      with positive serological screening, wherever possible. RESULTS: Use of this
      serological screening algorithm revealed a prevalence of undiagnosed CD in 5%-6%
      of first degree relatives of probands. CONCLUSION: Our data suggests that first
      degree relatives of individuals with CD should be screened for this condition.

PMID- 17203525
TI  - Management of digestive bleeding related to portal hypertension in cirrhotic
      patients: A French multicenter cross-sectional practice survey.
AB  - AIM: To investigate the conformity of management practices of gastrointestinal
      hemorrhage in cirrhotic patients with relevant guidelines. METHODS: A
      questionnaire on the management of digestive bleeding was completed for all
      consecutive cirrhotic patients admitted to 31 French hospitals. RESULTS: One
      hundred and twenty-six bleeding events were recorded. It was the first bleeding
      episode in 79 patients (63%), of whom 40 (51%) had a prior diagnosis of cirrhosis
      and 25 (32%) had previously undergone an endoscopy. The bleeding episode was a
      recurrence in 46 patients (37%). The median time between onset and admission was
      4 h, but exceeded 12 h in 42% of cases. There was an agreement between centers
      for early vasoactive drug administration (87% of cases), association with
      ligation (42%) more often than sclerosis (21%) at initial endoscopy, and
      antibiotic prophylaxis (64%). By contrast, prescription of beta-blockade alone or
      in combination (0 to 100%, P = 0.003) for secondary prophylaxis and lactulose
      (26% to 86%, P = 0.04), differed among centers. CONCLUSION: In French hospitals,
      management of bleeding related to portal hypertension in cirrhotic patients is
      generally in keeping with the consensus. Broad variability still remains
      concerning beta-blockade use for secondary prophylaxis. Screening for esophageal
      varices, the use of antibiotic prophylaxis and patients information need to be
      improved.

PMID- 17203526
TI  - H pylori infection and systemic antibodies to CagA and heat shock protein 60 in
      patients with coronary heart disease.
AB  - AIM: to determine the overall prevalence of H pylori and CagA positive H pylori
      infection and the prevalence of other bacterial and viral causes of chronic
      infection in patients with coronary heart disease (CHD), and the potential role
      of anti-heat-shock protein 60 (Hsp60) antibody response to these proteins in
      increasing the risk of CHD development. METHODS: Eighty patients with CHD and 160
      controls were employed. We also compared the levels of anti-heat-shock protein 60
      (Hsp60) antibodies in the two groups. The H pylori infection and the CagA status
      were determined serologically, using commercially available enzyme-linked
      immunosorbent assays (ELISA), and a Western blotting method developed in our
      laboratory. Systemic antibodies to Hsp60 were determined by a sandwich ELISA,
      using a polyclonal antibody to Hsp60 to sensitise polystyrene plates and a
      commercially available human Hsp60 as an antigen. RESULTS: The overall prevalence
      of H pylori infection was 78.7% (n = 63) in patients and 76.2% (n = 122) in
      controls (P = 0.07). Patients infected by CagA-positive (CagA+) H pylori strains
      were 71.4% (n = 45) vs 52.4% of infected controls (P = 0.030, OR = 2.27).
      Systemic levels of IgG to Hsp60 were increased in H pylori-negative patients
      compared with uninfected controls (P < 0.001) and CagA-positive infected patients
      compared with CagA-positive infected controls (P = 0.007). CONCLUSION: CagA
      positive H pylori infection may concur to the development of CHD; high levels of
      anti-Hsp60 antibodies may constitute a marker and/or a concomitant pathogenic
      factor of the disease.

PMID- 17203527
TI  - Non invasive evaluation of liver fibrosis in paediatric patients with
      nonalcoholic steatohepatitis.
AB  - AIM: To identify the independent predictors of hepatic fibrosis in 69 children
      with nonalcoholic steatohepatitis (NASH) due to nonalcoholic fatty liver disease
      (NAFLD). METHODS: All patients with clinically suspected NASH underwent liver
      biopsy as a confirmatory test. The following clinical and biochemical variables
      at baseline were examined as likely predictors of fibrosis at histology: age,
      body mass index (BMI), systolic blood pressure (SBP), dyastolic blood pressure
      (DBP), fasting glucose, fasting insulin, homeostatic model assessment for insulin
      resistence (HOMA-IR), cholesterol, tryglicerides, alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), AST/ALT ratio, gamma glutamil transferase (GT),
      platelet count, prothrombin time (PT). RESULTS: At histology 28 (40.6%) patients
      had no fibrosis and 41 (59.4%) had mild to bridging fibrosis. At multivariate
      analysis, BMI > 26.3 was the only independent predictor of fibrosis (OR = 5.85,
      95% CI = 1.6-21). CONCLUSION: BMI helps identify children with NASH who might
      have fibrotic deposition in the liver.

PMID- 17203528
TI  - Insulin sensitizers in treatment of nonalcoholic fatty liver disease: Systematic
      review.
AB  - AIM: To summarize the evidence available for the clinical effectiveness of
      insulin sensitizers in the treatment of nonalcoholic fatty liver disease (NAFLD)
      systematically. METHODS: Relevant articles were located using computer-assisted
      searches of Medline (1966-March 2006), EMBASE (1988-March 2006), CINAHL (1982
      March 2003), Educational Resource Information Center (1966-March 2006), Library,
      Information Science and Technology Abstracts (1967-March 2006), Cochrane Database
      of Systematic Reviews, Database of Abstracts of Reviews of Effects (1994-2006),
      dissertations in ProQuest and FirstSearch databases. Manual searches were made in
      the abstracts from meetings of the American Gastroenterological Association (1999
      2006), and the American Association for the Study of Liver Diseases (2003-2005).
      Studies were retrieved using the following selection criteria: (1) clinical
      trials using insulin sensitizers in subjects with NAFLD, (2) adult patients, (3)
      published as full manuscripts or abstracts, and (4) English, Spanish, German, and
      French languages only. Data were abstracted independently by two reviewers
      following standardized procedures. A face-to-face comparison of data was
      conducted to ensure the completeness and reliability of the abstraction process.
      RESULTS: Nine studies were included, six using metformin and three using
      thiazolidinediones. Only two studies were placebo-controlled trials. The median
      sample size for all studies was 18 subjects. In the placebo-controlled trials,
      metformin improved insulin resistance markers and liver function tests, but not
      histological scores. In the single-arm trials, metformin and thiazolidinediones
      improved insulin resistance markers and liver function tests, and beneficial
      histological changes were reported. There is limited high-quality information
      available from which to draw categorical conclusions about the clinical use of
      insulin sensitizers in NAFLD. CONCLUSION: Current information indicates that the
      use of insulin sensitizers in NAFLD improves insulin resistance and liver
      function. Histological changes must be corroborated in randomized controlled
      trials.

PMID- 17203529
TI  - Diagnosis and treatment of gallbladder perforation.
AB  - AIM: To present our clinical experience with gallbladder perforation cases.
      METHODS: Records of 332 patients who received medical and/or surgical treatment
      with the diagnosis of acute cholecystitis in our clinic between 1997 and 2006
      were reviewed retrospectively. Sixteen (4.8%) of those patients had gallbladder
      perforation. The parameters including age, gender, time from the onset of
      symptoms to the time of surgery, diagnostic procedures, surgical treatment,
      morbidity, and mortality were evaluated. RESULTS: Seven patients had type I
      gallbladder perforation, 7 type II gallbladder perforation, and 2 type III
      gallbladder perforation according to Niemeier's classification. The patients
      underwent surgery after administration of intravenous electrolyte solutions, and
      were treated with analgesics and antibiotics within the first 36 h (mean 9 h)
      after admission. Two patients died of sepsis and multiple organ failure in the
      early postoperative period. Subhepatic abscess, pelvic abscess, pneumonia,
      pancreatitis, and acute renal failure were found in 6 patients. CONCLUSION: Early
      diagnosis and emergency surgical treatment of gallbladder perforation are of
      crucial importance. Upper abdominal computerized tomography for acute
      cholecystitis patients may contribute to the preoperative diagnosis of
      gallbladder perforation.

PMID- 17203530
TI  - A head to head comparison of oral vs intravenous omeprazole for patients with
      bleeding peptic ulcers with a clean base, flat spots and adherent clots.
AB  - AIM: To compare the effect of intravenous and oral omeprazole in patients with
      bleeding peptic ulcers without high-risk stigmata. METHODS: This randomized study
      included 211 patients [112 receiving iv omeprazole protocol (Group 1), 99
      receiving po omeprazole 40 mg every 12 h (Group 2)] with a mean age of 52.7. In
      144 patients the ulcers showed a clean base, and in 46 the ulcers showed flat
      spots and in 21 old adherent clots. The endpoints were re-bleeding, surgery,
      hospital stay, blood transfusion and death. After discharge, re-bleeding and
      death were re-evaluated within 30 d. RESULTS: The study groups were similar with
      respect to baseline characteristics. Re-bleeding was recorded in 5 patients of
      Group 1 and in 4 patients of Group 2 (P = 0.879). Three patients in Group 1 and 2
      in Group 2 underwent surgery (P = 0.773). The mean length of hospital stay was
      4.6 +/- 1.6 d in Group 1 vs 4.5 +/- 2.6 d in Group 2 (P = 0.710); the mean
      amounts of blood transfusion were 1.9 +/- 1.1 units in Group 1 vs 2.1 +/- 1.7
      units in Group 2 (P = 0.350). Four patients, two in each group died (P = 0.981).
      After discharge, a new bleeding occurred in 2 patients of Group 1 and in 1
      patient of Group 2, and one patient from Group 1 died. CONCLUSION: We demonstrate
      that the effect of oral omeprazole is as effective as intravenous therapy in
      terms of re-bleeding, surgery, transfusion requirements, hospitalization and
      mortality in patients with bleeding ulcers with low risk stigmata. These patients
      can be treated effectively with oral omeprazole.

PMID- 17203531
TI  - Depression in patients with irritable bowel syndrome in Jos, Nigeria.
AB  - AIM: To study the brain-gut interaction and the effect of behavioral or
      psychiatric conditions on irritable bowel syndrome (IBS) in an African
      population. METHODS: IBS was diagnosed using the Rome II diagnostic criteria. The
      entry of each patient was confirmed following detailed explanations of the
      questions. Four hundred and eighteen patients were studied. Subjects satisfying
      the Rome II criteria for IBS were physically examined and stool microscopy was
      done to identify the presence of "alarm factors". Depression was diagnosed using
      the symptom-check list adapted from the Research Diagnostic Criteria (DSM-IV) of
      the American Psychiatric Association. RESULTS: Seventy-five (56.8%) of the 132
      IBS patients were depressed whereas only 54 (20.1%) of the 268 non-IBS patients
      were depressed. There was a significant relationship between IBS and depression
      (chi2 = 54.29, Odds ratio = 5.21, 56.8 +/- 8.4 vs 20.1 +/- 5.2, P = 0.001). Even
      though constipation predominant IBS patients were more likely to be depressed, no
      significant relationship was found between the subtype of IBS and depression
      (chi2 = 0.02, OR = 0.95, P = 0.68). CONCLUSION: IBS is significantly associated
      with major depression but not gender and bowel subtypes of the patients. Patients
      with IBS need to be evaluated for depression due to the highly significant
      relationship between the two conditions.

PMID- 17203532
TI  - Novel MLH1 frameshift mutation in an extended hereditary nonpolyposis colorectal
      cancer family.
AB  - AIM: To present novel frameshift mutation c.31delC [p.L11X] in the MLH1 gene
      identified in an extended Bulgarian hereditary non-polyposis colorectal cancer
      (HNPCC) family and to analyze the molecular and clinical findings within the
      pedigree concerning the proposal of adequate individual prophylactic strategy for
      all mutation carriers. METHODS: The pedigree of the family consists of 42 members
      in four generations. Search for mutations in the MLH1 and hMSH2 genes was
      performed in the proband. After PCR amplification of all exons including flanking
      intronic regions, amplicons were directly sequenced. RESULTS: The mutation was
      found in nine from the thirteen pedigree members who signed informed consent to
      participate in the study. In three adenocarcinomas, microsatellite instability
      and lack of the MLH1 protein expression were detected. The only one tubulovillous
      adenoma analyzed was microsatellite stable and the MLH1 protein showed an intact
      staining. CONCLUSION: The newly described mutation c.31delC is HNPCC causative.
      Besides the typical clinical features of the syndrome, we found a specific
      pathologic manifestation such as moderate to high differentiated adenocarcinomas
      of the colon. One of the mutation carriers developed a benign giant cell soft
      tissue tumor. The primary tumor localizations were frequently extracolonic and
      detailed yearly gastrointestinal and gynecological examinations have been
      proposed to the mutation carriers. We emphasize the importance of including the
      HNPCC genetic counseling and testing as well in the following surveillance of all
      patients at risk in the services covered by the health insurance in Bulgaria.

PMID- 17203533
TI  - Expression patterns and action analysis of genes associated with physiological
      responses during rat liver regeneration: Innate immune response.
AB  - AIM: To study the relationship between innate immune response and liver
      regeneration (LR) at transcriptional level. METHODS: Genes associated with innate
      immunity response were obtained by collecting the data from databases and
      retrieving articles. Gene expression changes in rat regenerating liver were
      detected by rat genome 230 2.0 array. RESULTS: A total of 85 genes were found to
      be associated with LR. The initially and totally expressed number of genes at the
      phases of initiation [0.5-4 h after partial hepatectomy (PH)], transition from G0
      to G1 (4-6 h after PH), cell proliferation (6-66 h after PH), cell
      differentiation and structure-function reconstruction (66-168 h after PH) was 36,
      9, 47, 4 and 36, 26, 78, 50, respectively, illustrating that the associated genes
      were mainly triggered at the initial phase of LR and worked at different phases.
      According to their expression similarity, these genes were classified into 5
      types: 41 up-regulated, 4 predominantly up-regulated, 26 down-regulated, 6
      predominantly down-regulated, and 8 approximately up/down-regulated genes,
      respectively. The expression of these genes was up-regulated 350 times and down
      regulated 129 times respectively, demonstrating that the expression of most genes
      was enhanced while the expression of a small number of genes was decreased during
      LR. Their time relevance was classified into 14 groups, showing that the cellular
      physiological and biochemical activities during LR were staggered. According to
      the gene expression patterns, they were classified into 28 types, indicating that
      the cellular physiological and biochemical activities were diverse and
      complicated during LR. CONCLUSION: Congenital cellular immunity is enhanced
      mainly in the forepart, prophase and anaphase of LR while congenital molecular
      immunity is increased dominantly in the forepart and anaphase of LR. A total of
      85 genes associated with LR play an important role in innate immunity.

PMID- 17203534
TI  - Overexpression of Ets-like protein 1 in human esophageal squamous cell carcinoma.
AB  - AIM: To study the expression pattern of Ets-like protein 1 (Elk-1) in human
      esophageal squamous cell carcinoma (ESCC) and to analyze its relationship with
      clinicopathologic parameters. METHODS: The expression of Elk-1 in fresh
      esophageal cancer tissues and their corresponding normal mucosae was detected
      immunohistochemically (IHC) by means of tissue microarray (TMA). Its correlation
      with clinical characteristics was evaluated and analyzed by univariate analysis.
      All statistical analyses were performed by SPSS version 13.0. RESULTS: Expression
      level of transcription factor Elk-1 increased in 78.5% (84/107) ESCC tissues
      compared with their matched normal esophageal epithelium. However, the expression
      of Elk-1 did not show any obvious correlation with degree of differentiation of
      esophageal carcinoma (in well-differentiated, moderately-differentiated and
      poorly-differentiated tumors, the increased expression was 7/8, 60/74, and 19/25,
      respectively, P > 0.05). Moreover, no obvious correlation was found with lymph
      node metastasis and depth of invasion. CONCLUSION: Increased expression of
      transcription factor Elk-1 may play an important role in esophageal
      carcinogenesis.

PMID- 17203535
TI  - Colonic exclusion and combined therapy for refractory constipation.
AB  - AIM: To investigate the therapeutic effectiveness of colonic exclusion and
      combined therapy for refractory constipation. METHODS: Thirty-two patients with
      refractory constipation were randomly divided into treatment group (n = 14) and
      control group (n = 18). Fourteen patients in treatment group underwent colonic
      exclusion and end-to-side colorectal anastomosis. Eighteen patients in control
      group received subtotal colectomy and end-to-end colorectal anastomosis. The
      therapeutic effects of the operations were assessed by comparing the surgical
      time, incision length, volume of blood losses, hospital stay, recovery rate and
      complication incidence. All patients received long-term follow-up. RESULTS: All
      operations were successful and patients recovered fully after the operations. In
      comparison of treatment group and control group, the surgical time (h), incision
      length (cm), volume of blood losses (mL), hospital stay (d) were 87 +/- 16 min vs
      194 +/- 23 min (t = 9.85), 10.4 +/- 0.5 cm vs 21.2 +/- 1.8 cm (t = 14.26), 79.5
      +/- 31.3 mL vs 286.3 +/- 49.2 mL (t = 17.24), and 11.8 +/- 2.4 d vs 18.6 +/- 2.6
      d (t = 6.91), respectively (P < 0.001 for all). The recovery rate and
      complication incidence were 85.7% vs 88.9% (P = 0.14 > 0.05), 21.4% vs 33.3% (P =
      0.73 > 0.05), respectively. CONCLUSION: Colonic exclusion has better therapeutic
      efficacy on refractory constipation. It has many advantages such as shorter
      surgical time, smaller incision, fewer blood losses and shorter hospital stay.

PMID- 17203536
TI  - CT diagnosis of 52 patients with lymphoma in abdominal lymph nodes.
AB  - AIM: To assess CT manifestations and its diagnostic value for lymphoma in the
      abdominal lymph nodes (LALN). METHODS: CT findings in 52 cases of LALN proved by
      surgery or biopsy, including Hodgkin's disease (HD) in 16 cases and non-Hodgkin's
      lymphoma (NHL) in 36 cases, were retrospectively analyzed. RESULTS: (1) CT
      manifestations based on distribution of the lesions of LALN: Solitary mass type
      was found in 10 cases, including solitary, round, uniform-density, enlarged lymph
      nodes in 3 cases; and multiple, enlarged lymph nodes fusing into singular lobular
      mass in 7 cases. Thirty-four cases of multiple-nodular type showed multiple,
      round, enlarged lymph nodes with uniform density and clear margins. Vessels
      embedded signs, including mesenteric vessels, renal vessels, abdominal aorta or
      inferior vena cava, were seen in 6 cases, and duodenum-embedded signs were seen
      in 2 cases. Eight cases of diffuse type showed characteristic "cobblestone
      signs". (2) CT manifestations correlated with pathological type: CT
      manifestations of 12 cases of HD were different from those of 40 cases of NHL in
      distribution, size, quantity and fused lesion of enlarged lymph nodes. (3) Twenty
      eight cases of 52 patients were accompanied with extra-nodal lymphoma in the
      abdomen, especially gastrointestinal lymphoma, which had characteristic CT
      findings. (4) In follow-up examinations, CT images showed uniform, heterogeneous
      or rim enhancement in 15 cases, and occasional calcifications accompanied with
      reduction of the lesion size and quantity in 12 cases, whereas the lesions
      disappeared in 3 cases after treatment. CONCLUSION: CT images show many
      characteristic manifestations valuable for qualitative diagnosis of LALN, and it
      is also helpful for pathological classification of LALN and therapeutic
      evaluation in follow-up of patients.

PMID- 17203537
TI  - Sporadic ganglioneuromatosis of esophagogastric junction in a patient with gastro
      esophageal reflux disorder and intestinal metaplasia.
AB  - A 58-year-old female with a recurrent history of upper abdominal pain and
      intermittent dysphagia underwent endoscopic evaluation that demonstrated an
      irregular and nodular esophago-gastric (EG) junction and grade I erosive
      esophagitis. Biopsies showed prominent intestinal metaplasia of Barrett's type
      without dysplasia, chronic inflammation and multiple aggregates of large cells
      within the mucosal lamina propria, some with spindle shaped nuclei.
      Immunohistochemistry stains for keratins AE-1/AE-3 were negative, while S-100 and
      NSE were positive. This, together with routine stains, was diagnostic for mucosal
      ganglioneuromatosis. The background of chronic inflammation with intestinal type
      metaplasia was consistent with long-term reflux esophagitis. No evidence of
      achalasia was seen. Biopsies of gastric antrum and fundus were unremarkable,
      without ganglioneural proliferation. Colonoscopy was unremarkable. No genetic
      syndromes were identified in the patient including familial adenomatous polyposis
      and multiple endocrine neoplasia type IIb (MEN IIb). Iansoprazole (Prevacid) was
      started by oral administration each day with partial relief of symptoms.
      Subsequent esophagogastroscopy repeated at 4 mo showed normal appearing EG
      junction. Esophageal manometry revealed a mild non-specific lower esophageal
      motility disorder. Mild motor dysfunction is seen with gastro-esophageal reflux
      disease (GERD) and we feel that the demonstration of localized
      ganglioneuromatosis was not likely related etiologically. In the absence of
      findings that might suggest neural hypertrophy, such as achalasia, the nodular
      mucosal irregularity seen with this instance of ganglioneuromatosis may, however,
      have exacerbated the patient's reflux.

PMID- 17203538
TI  - Osteoclast-like giant cell tumors of the pancreas and liver.
AB  - Osteoclast-like giant cell tumors (OGCT) are rare abdominal tumors, which mainly
      occur in the pancreas. The neoplasms are composed of two distinct cell
      populations and frequently show an inhomogenous appearance with cystic
      structures. However, due to the rarity of these tumors, only very limited
      clinical data are available. Imaging features and sonographic appearance have
      hardly been characterized. Here we report on two cases of osteoclast-like giant
      cell tumors, one located within the pancreas, the other within the liver, in
      which OGCTs are extremely rare. Both patients were investigated by contrast
      sonography, which demonstrated a complex, partly cystic and strongly vascularized
      tumor within the head of the pancreas in the first patient and a large,
      hypervascularized neoplasm with calcifications within the liver in the second
      patient. The liver OGCT responded well to a combination of carboplatin, etoposide
      and paclitaxel. With a combination of surgical resection, radiofrequency ablation
      and chemotherapy, the patient's survival is currently more than 15 mo, making him
      the longest survivor with an OGCT of the liver to date.

PMID- 17203539
TI  - Readers offer insight on food animal veterinarian shortage.

PMID- 17203540
TI  - Images in emergency medicine. Molar pregnancy.

PMID- 17203541
TI  - Emergency department flow and the boarded patient: how to get admitted patients
      upstairs.

PMID- 17203542
TI  - Suburban sprawl: where does emergency medicine fit on the map?

PMID- 17203543
TI  - Evidence-based emergency medicine/rational clinical examination abstract. Does
      this patient have influenza?

PMID- 17203544
TI  - Evidence-based emergency medicine/rational clinical examination abstract. Does
      this woman have an acute uncomplicated urinary tract infection?

PMID- 17203545
TI  - Developments in European preventive cardiology.

PMID- 17203546
TI  - Chest mass and anemia.

PMID- 17203547
TI  - Proposals for the Responsible Use of Racial and Ethnic Categories in Biomedical
      Research: Where Do We Go From Here? Proceedings of a conference, April 2005.

PMID- 17203548
TI  - The portrayal of coma in contemporary motion pictures.

PMID- 17203549
TI  - Iceland plans reigned in.

PMID- 17203550
TI  - UK banking on consent.

PMID- 17203551
TI  - Forest shifts bolster long-term hopes.

PMID- 17203552
TI  - Q & A. Michael J. Ryan.

PMID- 17203553
TI  - Apparent clearance of sirolimus in heart transplant recipients: impact of primary
      diagnosis and serum lipids.
AB  - The study was aimed to identify factors affecting sirolimus apparent clearance
      (CL/F) in de novo heart transplant recipients using a population pharmacokinetic
      approach. A total of 31 patients (7 female and 24 male) originally included in a
      formal clinical trial, contributed 524 sirolimus blood concentrations with the
      time after dose ranging from 11.08 to 31.83 hours. Sirolimus concentrations were
      measured using liquid chromatography-tandem mass spectrometry and data analysis
      was carried out using NONMEM (Globomax LLC, Hanover, MD) software. Factors
      screened included age, weight, gender, primary diagnosis, biochemical and
      hematological indices, cyclosporine dose, days post-transplant and potential
      interacting medications. The predictive performance of the final model was
      evaluated using a data-splitting method. Sirolimus apparent clearance (CL/F) was
      decreased by 20.8% for every 100 mg increase in cyclosporine daily dose and was
      62.1% lower in patients with primary diagnosis of ischemic heart disease (IHD).
      Sirolimus apparent clearance was 37.8% lower when triglyceride was greater than 2
      mmol/L. Based on the final model, the average values for sirolimus CL/F and
      apparent volume of distribution were 7.09 and 1350 L/h, respectively. Inter
      subject variability in CL/F was 27.5% and residual random error was 24.1%. This
      study identified cyclosporine dose, hypertriglyceridemia and primary diagnosis of
      IHD as the most important factors affecting sirolimus CL/F. This information may
      assist in dose individualization of sirolimus in heart transplant recipients.

PMID- 17203554
TI  - Model mentors.

PMID- 17203555
TI  - The efficacy of adipokines and indices of metabolic syndrome as predictors of
      severe obesity-related hepatic steatosis.
AB  - The aim of this study was to investigate adiponectin, leptin, and metabolic
      syndrome as predictors of the severity of obesity-related steatosis. By
      ultrasonography steatosis-positive (cases) subjects (n = 141) were compared with
      controls (n = 111). Demographic and anthropometric data and serum concentrations
      of adiponectin, leptin, and insulin were measured. The impact of several criteria
      of metabolic syndrome, serum adiponectin concentrations, and serum leptin
      concentrations were tested using a multivariate logistic regression analysis. The
      frequency of metabolic syndrome was higher in cases (44.0% versus 9.2%; P <
      .0001). Cases were older and had higher insulin resistance, waist circumference,
      and lower concentrations of adiponectin (all P < .001). The upper adiponectin
      quartile was associated with a lesser grade of steatosis. Metabolic syndrome and
      adiponectin concentrations were independently associated with the probability of
      steatosis. In conclusion, adipokines and metabolic syndrome are useful indices
      for the prediction of the severity of obesity-related steatosis.

PMID- 17203556
TI  - Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis:
      relationship with inflammation, activity, and density of the bacterium.
AB  - We sought to study the relationship between serum pepsinogens and different
      histopathologic features of Helicobacter pylori-related chronic gastritis. One
      hundred forty-nine consecutive dyspeptic patients underwent endoscopy with
      biopsies; serum pepsinogens I and II were measured by immunoassay. Serum levels
      of pepsinogens (sPG) were significantly correlated with H. pylori density both of
      the corpus (sPGI: r = 0.32, P < .001; sPGII: r = 0.56, P < .001) and antrum
      (sPGI: r = 0.41, P < .001; sPGII: r = 0.43, P < .001) as well as with chronic
      inflammation (sPGI: r = 0.26, P < .001; sPGII: r = 0.49, P < .001) and activity
      (sPGI: r = 0.38, P < .001; sPGII: r = 0.50, P < .001) in the antrum. Only sPGII
      was correlated with chronic inflammation (r = 0.44, P < .001) and activity (r =
      0.40, P < .001) in the corpus. SPGI was inversely correlated with atrophy (r = 
      0.33, P < .001) and intestinal metaplasia (r = -0.37, P < .001) in the corpus.
      sPGII levels could be considered as markers of gastric inflammation all over in
      the stomach. sPGI levels are inversely related to atrophic body gastritis.

PMID- 17203557
TI  - Influence of Trypanosoma cruzi chronic infection in the depletion of esophageal
      neurons in Calomys callosus.
AB  - The extent of neuronal loss was studied in this work, in aged female Calomys
      callosus infected with the MORC-1 strain of Trypanosoma cruzi. Fifteen months
      after infection, one group of animals was immunosuppressed with cyclophosphamide
      (CY). Sections of the distal esophagus were collected and stained with cresyl
      violet. The neuron count was significantly different among groups, with enhanced
      neuronal loss in the infected group in comparison with the control aged
      noninfected group. Partial protection against neuronal destruction was observed
      in animals immunosuppressed with CY. The morphometry of the neuronal body
      displayed significant alterations concerning area, shape coefficient, and contour
      index that were statistically increased for the CY-infected group. These results
      indicate a protective role for CY against neuronal destruction.

PMID- 17203558
TI  - [Uninary infection due to non-01, non-0139 Vibrio cholerae].

PMID- 17203559
TI  - Response to Richard B. Miller's "Children, Ethics, and Modern Medicine".

PMID- 17203560
TI  - The expert consensus guideline series. Treatment of dementia and its behavioral
      disturbances.

PMID- 17203561
TI  - The expert consensus guideline series. Treatment of dementia and its behavioral
      disturbances. Introduction: methods, commentary, and summary.
AB  - OBJECTIVES: New treatment options for dementia and its behavioral disturbances
      have become available since publication of The Expert Consensus Guidelines on the
      Treatment of Agitation in Older Persons with Dementia in 1998. While only 2
      cholinesterase inhibitors, donepezil and tacrine, were available in 1998, 3 new
      cognitive-enhancing agents have been introduced since that time as well as
      several new atypical antipsychotics and antidepressants. However, there are still
      limited data from controlled studies to guide clinicians in choosing among these
      agents and sequencing and combining treatments. We therefore conducted a new
      survey study of expert opinion on the treatment of cognitive impairment and
      behavioral disturbances associated with dementia. METHODS: Based on a literature
      review, a 61-question survey was developed with 1,225 options. Most options were
      scored using a modified version of the RAND 9-point scale for rating
      appropriateness of medical decisions. For other options, the experts were asked
      to write in answers. The survey was sent to 50 North American experts on
      dementia, 100% of whom completed it. In analyzing responses to items rated on the
      9-point scale, consensus was defined as a nonrandom distribution of scores by chi
      square "goodness-of-fit" test. Based on the 95% confidence interval around the
      mean, we assigned a categorical rank (first line/preferred, second
      line/alternate, third line/usually inappropriate) to each option. Guidelines
      indicating preferred treatment strategies were then developed for selected
      clinical situations. RESULTS: For patients at risk for dementia, the experts
      recommended control of hypertension and diabetes. They also recommended aspirin
      and would consider a lipid-lowering agent in patients at risk for vascular
      dementia. Cholinesterase inhibitors were an option for patients with mild
      cognitive impairment (i.e., at risk for Alzheimer's dementia [AD]). To slow
      cognitive impairment in mild/moderate AD, the experts recommended a
      cholinesterase inhibitor alone or combined with vitamin E. Donepezil and
      galantamine were the preferred cholinesterase inhibitors. The experts recommended
      combining a cholinesterase inhibitor with a N-methyl-D-aspartate (NMDA)
      antagonist (e.g., memantine) if a patient with mild/moderate dementia has an
      inadequate response to monotherapy. Control of hypertension and diabetes was the
      treatment of choice, in patients with mild/moderate vascular or mixed AD/vascular
      dementia, with aspirin another first-line option. Cholinesterase inhibitors were
      also a first-line option for mild/moderate mixed AD/vascular dementia. Among
      nonpharmacological interventions for mild/moderate dementia, the experts
      recommended caregiver education, supportive therapy for caregivers, referral to
      day treatment, exercise programs, and respite care. For moderate/severe AD or
      mixed AD/vascular dementia, the experts recommended combining an NMDA antagonist
      with a cholinesterase inhibitor. For moderate/severe vascular or mixed
      AD/vascular dementia, they recommended control of hypertension and diabetes. The
      experts' ratings underscore the importance of nonpharmacological strategies aimed
      at reducing caregiver burden in more severe dementia. Management of agitation and
      other behavioral disturbances was another focus of this study. The experts
      recommended using an atypical antipsychotic for agitation associated with
      delirium, psychosis, aggression, or anger. They would also consider divalproex to
      manage anger with a risk of physical aggression. Selective serotonin reuptake
      inhibitors were recommended for the treatment of depression or anxiety in
      patients with dementia. Benzodiazepines or atypical antipsychotics were viewed as
      short-term options for acute anxiety. Trazodone was recommended for insomnia. The
      experts also gave recommendations concerning dosage levels, duration of
      treatment, and choice of medications for patients with different complicating
      conditions. CONCLUSIONS: The experts reached high levels of consensus on key
      steps in treating dementia and associated behavioral disturbances. Within the
      limits of expert opinion and with the expectation that new research data will
      take precedence, these guidelines may provide direction for clinicians offering
      care to patients with dementia.

PMID- 17203562
TI  - A mission to convert.
AB  - Primarily a review of Richard Dawkins' book, The God delusion (Boston: Houghton
      Mifflin, 2006).

PMID- 17203563
TI  - On Clifford Geertz: field notes from the classroom.

PMID- 17203564
TI  - The perils of Antoinette.

PMID- 17203565
TI  - [The Spanish Society of Internal Medicine (SEMI). Achievements attained and
      pending challenges. September 2006].

PMID- 17203566
TI  - [Paludism: emergent diagnosis. Descriptive study of 25 cases].
AB  - INTRODUCTION: During the last years, the number of patients with paludism in
      occidental countries has raised, specially due to the increase of immigration
      from endemic areas and to the augmentation of international journeys to those
      area. MATERIAL AND METHODS: A descriptive and retrospective study of the cases of
      paludism diagnosed at the Hospital Universitario La Princesa, was performed
      between January 1995 and December 2002. RESULT: Twenty-five patients were
      diagnosed of paludism. More than half of patients (15) were immigrants coming
      from endemic areas and the rest were Spanish patients who had traveled to endemic
      places, most of them to Africa. A transfusional case was detected. Twenty-two
      patients didn't take prophylaxis therapy. The most usual subtype of Plasmodium
      was P. falciparum. Symptoms were not specific and fever was a constant feature.
      The period of time between the arrival in spain and the moment of diagnosis range
      from one to four weeks (21 patients). DISCUSSION: It is important to search for
      paludism infection in patients with maintained fever who have arrived from tropic
      regions. Prophylaxis therapy does not exclude this possibility. Response to
      treatment is usually satisfactory.

PMID- 17203567
TI  - [Validity of Framingham criteria as a clinical test for systolic heart failure].
AB  - BACKGROUND: To assess validity and clinical usefulness of the Framingham clinical
      criteria for the diagnosis of systolic heart failure. METHODS: A descriptive
      cross-sectional trial. The study population was made up of the patients who went
      to the emergency Department at the Hospital de Elche, Elche, Spain, with cardiac
      dyspnoea. The method applied was a validation study in which a value of 0.45 of
      the left ventricular ejection fraction was taken as a sign of certitude and
      compared to the presence/absence of the Framingham clinical criteria. The study
      indicators were: sensitivity, specificity, positive predictive value, negative
      predictive value, positive probability quotient and negative probability
      quotient. RESULTS: The trial included 224 patients. The most frequent major
      criteria were: lung rales (93%), megalocardia (85.9%) and paroxysmal nocturnal
      dyspnoea or orthopnea (75.8%). The most important minor criteria were: exertional
      dyspnoea (89.2%), pleural effusion (82.8%) and lower limb oedemas (70.1%). The
      values that were considered as a sign of left ventricular systolic failure (0.45)
      proved to have good sensitivity and positive predictive value (96.4% and 97%,
      respectively). Clinical usefulness indicators obtained a positive probability
      quotient of 1.52 and a negative predictive value of 0.09. CONCLUSIONS: The
      Framingham clinical criteria have excellent sensitivity but poor specificity. The
      absence of these criteria totally excludes the diagnosis if the value of the left
      ventricular ejection fraction is 0.45 (A category) but their presence does not
      confirm the diagnosis because of the high amount of false-positive findings (D
      category).

PMID- 17203568
TI  - Transmission of human herpesvirus 8 by blood transfusion.

PMID- 17203569
TI  - Delays in the diagnosis of autistic spectrum disorder in a community child and
      adolescent mental health service(CAMHS).

PMID- 17203570
TI  - Guidelines--Rome III Diagnostic Criteria for Functional Gastrointestinal
      Disorders.

PMID- 17203571
TI  - Cancer biomarkers. Preface.

PMID- 17203572
TI  - Dental arch shape and size in Malay schoolchildren with Class II malocclusion.
AB  - AIM: To quantify and localise differences in Class I and Class II dental arches
      in Malay schoolchildren. METHODS: The subjects were 50 Malay schoolchildren (Mean
      age: 15 + 0.7 years) with either Class I (N = 25) or Class II (N = 25)
      malocclusions. Fourteen homologous landmarks on the upper and lower study models
      of the subjects were digitised using MorphoStudio software, and the Procrustes
      means were computed. The mean Class I and Class II configurations were subjected
      to ftests and finite element analysis. RESULTS: Normalised upper arch Class I and
      Class II configurations were statistically different (p < 0.05), but the lower
      arches were not. However, normalised Class II linear parameters were
      statistically smaller in the upper arch and larger in the lower arch. The upper
      Class II dental arch was narrower by 15 per cent and asymmetric changes in size
      (11-20 per cent) were localised in the labial and buccal regions of the lower
      Class II arch. CONCLUSIONS: Size and shape differences between Class I and Class
      II dental arches can be identified with finite element analysis.

PMID- 17203573
TI  - Myosin heavy chain isoform composition of human masseter muscle from subjects
      with different mandibular plane angles.
AB  - AIM: To investigate the presence of myosin heavy chain isoforms in human masseter
      muscle and to describe any differences in orthognathic surgery patients with
      different mandibular plane angles. METHOD: Biopsies were obtained from the
      anterior border of the superficial masseter muscle in 18 patients undergoing
      various orthognathic procedures. Myosin heavy chain isoforms were isolated and
      analysed by SDS-PAGE gel electrophoresis. Steiner's mandibular plane angles were
      measured from pretreatment lateral cephalometric radiographs and used to classify
      the vertical dimension of each subject. RESULTS: Despite the fact that there was
      wide individual variation, there appeared to be no direct association between the
      presence of myosin heavy chain isoforms and specific vertical facial patterns.
      Type I myosin heavy chain isoform was the most common isoform found in all
      subjects. More Type IIA myosin heavy chain isoforms were observed in
      dolichofacial subjects. There were no differences between genders in myosin heavy
      chain expression. CONCLUSION: A wide variation of myosin heavy chain isoforms
      exists in the masseter muscle of individuals with different mandibular plane
      angles. Further investigations involving larger sample sizes and the
      incorporation of bite-force measurements may help to clarify the relationship
      between mandibular muscle characteristics and the vertical facial dimension.

PMID- 17203574
TI  - An investigation of the forces used by clinicians to open spaces with coil
      springs.
AB  - AIMS: To determine the forces applied by coil springs used to open spaces for
      blocked out lateral incisors, and to compare the actual forces used with
      clinicans' concepts of an 'ideal' force. METHODS: Twelve postgraduate orthodontic
      students (7M, 5F) and 12 orthodontic tutors (9M, 3F) participated in this study.
      They were asked to state what they considered was an ideal orthodontic force, and
      then to cut appropriate lengths of stainless steel and nickel titanium open coil
      springs to open spaces for blocked out maxillary and mandibular permanent lateral
      incisors on a typodont set-up. The forces generated by the open coil springs were
      measured and compared to the stated ideal forces. RESULTS: The mean ideal force
      was 76.75 g (Range: 25-200 g). The mean applied force was 314 g (Range: 21-519
      g). There were no significant differences in the forces used by the male and
      female postgraduates, but the male tutors used a significantly higher force than
      the male postgraduate students (p = 0.007) and the female tutors (p < 0.001). The
      female tutors used a significantly lower force than the female postgraduates (p =
      0.024) and the male postgraduates (p = 0.003). Higher forces were produced by the
      stainless steel coil springs in both arches (Maxillary arch: p = 0.007;
      Mandibular arch: p < 0.005). CONCLUSIONS: The clinicians could not agree on an
      ideal force to open spaces for blocked out lateral incisors. There were
      substantial differences between the forces applied by the coil springs and the
      forces considered by the clinicians to be ideal. There were large differences in
      the forces used by the different groups of orthodontists.

PMID- 17203575
TI  - M/F ratios of four different closing loops: 3D analysis using the finite element
      method (FEM).
AB  - BACKGROUND: It has been claimed that the opus loop is capable of delivering a
      constant and optimum M/F ratio without the need for gable bends. OBJECTIVE: To
      compare the forces, moments and moment/force (M/F) ratios of the opus loop, L
      loop, T-loop and vertical helical closing loop (VHC loop) in a segmented arch
      with the finite element method (FEM). METHODS: The FEM was used to compare 3D
      models of closing loops in rectangular (0.016 x 0.022 inch) stainless steel wire.
      The L-, T- and VHC loops were designed with and without preactivation bends. The
      opus loop had no preactivation bends. The T-Loops were 10 mm in height and 10 mm
      in length. The horizontal and vertical forces, the moments and the M/F ratios at
      the alpha and beta ends were recorded at 0, 0. 1, 0.4, 0.7 and 1 mm intervals.
      RESULTS: The highest horizontal and vertical forces were produced by the L-loop
      (with and without preactivation bends) and in most cases the lowest forces were
      produced by the VHC loop. Loops with preactivation bends produced marked changes
      in the M/F ratio and loops without preactivation bends low, but relatively
      constant, M/F ratios over the full range of activation. Of the loops modelled
      without preactivation bends the opus and T-loop had the highest M/F ratios (7.20 
      7.67 mm at the anterior ends). CONCLUSION: Stainless steel opus and T-loops
      without preactivation bends had constant M/F ratios, but both loops failed to
      deliver the optimum M/F ratio of 10:1.

PMID- 17203576
TI  - Assessment of growth activity in the mandibular condyles by single-photon
      emission computed tomography (SPECT).
AB  - BACKGROUND: Unilateral condylar hyperplasia can lead to marked and disfiguring
      changes in the face and occlusion. A method of determining side-to-side
      differences in condylar activity is an important step in managing this condition.
      AIMS: To determine the growth activity in normal mandibular condyles and to
      devise an index of side-to-side differences in condylar activity in different
      individuals. METHODS: Thirty eight patients, ranging from 13 to 34 years, who
      were undergoing skeletal scintigraphy for a variety of conditions agreed to
      participate in this study. No subjects had clinical or radiographic signs of
      mandibular hyperplasia. After injection of 25 mci Tc99 the uptake by the right
      and left mandibular condyles was measured and the side-to-side differences used
      to calculate an index. RESULTS: The maximum side-to-side differences were 6.2 per
      cent (Right side versus left side: 53.1 per cent and 46.9 per cent respectively)
      in the male patients and 5.7 per cent in the female patients (Right side versus
      Left side: 52.85 per cent and 47.15 per cent respectively). CONCLUSIONS: The
      variation in growth activity in normal right and left mandibular condyles was
      less than 6.2 per cent.

PMID- 17203577
TI  - Use of miniscrews as temporary anchorage devices in orthodontic practice. I-
      Introduction.
AB  - AIM: To describe the use of miniscrews as temporary anchorage devices to
      facilitate mesial, distal and vertical orthodontic tooth movement. METHOD: The
      development of miniscrews and the direct and indirect application of forces from
      these devices are described. Case reports will be given in a second paper.

PMID- 17203578
TI  - The influence of ligation on frictional resistance to sliding during repeated
      displacement.
AB  - OBJECTIVE: To determine if the type of ligation influences the frictional
      resistance between stainless steel wire and brackets when the wire is subjected
      to repeated vertical displacements. METHODS: Eight different types of ligation
      were used to secure a length of stainless steel wire in three stainless steel
      twin brackets. The wire was subjected to repeated vertical displacements in a
      simulated extraction space. Eighty per cent of the minimum force required to
      overcome static friction (F-m) between the wire and brackets was applied to the
      wire for eight minutes and any sliding measured. RESULTS: Frictional resistance
      to sliding was least when stainless steel ligatures twisted in a figure 8 pattern
      until taut then untwisted one quarter turn were used, and greatest when
      elastomeric modules in a figure 8 pattern (EM8) were used. The F-m difference
      between fully engaged standard and Super Slick elastomeric modules was
      significantly different (p = 0.007). The frictional resistance to sliding fell
      when the wire was secured with either of these two methods and subjected to
      vertical displacement loads. There was no significant difference in the rate of
      wire movement between these modules. CONCLUSION: Repeated vertical displacement
      reduced the frictional resistance to sliding for all methods of ligation except
      EM8.

PMID- 17203579
TI  - Static frictional resistances of polycrystalline ceramic brackets with metal slot
      inserts.
AB  - AIMS: To compare the static frictional resistances of polycrystalline ceramic
      brackets with a gold slot insert (Desire), a stainless steel slot insert
      (Clarity), a conventional polycrystalline ceramic bracket (Transcend 6000) and a
      stainless steel bracket (Ultratrimm). METHODS: Twenty five brackets of each type
      were tested by sliding against straight lengths of 0.019 x 0.025 inch rectangular
      stainless steel wire. During the tests the brackets and wire were lubricated with
      artificial saliva. Static frictional forces at three different binding
      angulations (0, 5 and 10 degrees) were measured for all brackets. RESULTS:
      Statistically significant increases in static frictional resistance were found as
      the bracket/wire angulation increased from 0 through 5 to 10 degrees for all
      bracket types. At angulations below the critical binding angle the Ultratrimm
      brackets produced the greatest friction and the Transcend 6000 brackets produced
      the least friction. As the angulation increased the Transcend 6000 brackets
      produced greater friction than the other brackets. At the highest angulation (10
      degrees), the Ultratrimm brackets produced significantly less friction and the
      Transcend 6000 brackets produced significantly more friction than the other
      brackets. The Desire and Clarity brackets produced comparable results: there were
      no statistically significant differences between these two brackets for static
      friction at any of the angulations. CONCLUSIONS: Polycrystalline ceramic brackets
      with either stainless steel or gold slot inserts produced similar static
      frictional resistances to sliding. At binding angulations, the brackets with
      inserts demonstrated consistently lower static frictional resistances than a
      conventional ceramic bracket.

PMID- 17203580
TI  - Root resorption after orthodontic treatment.
AB  - BACKGROUND: Orthodontic treatment can result in root resorption. OBJECTIVE: To
      determine if apical root resorption is related to the type of appliance used
      and/or the direction and amount of tooth movement. METHODS: The pre- and post
      treatment tooth lengths of the maxillary and mandibular first molars and incisors
      were measured on panoramic radiographs of 114 subjects. Associations between
      changes in the lengths of the incisors and positional changes in the upper and
      lower central incisors were determined for 45 subjects with pre- and post
      treatment cephalometric radiographs. RESULTS: Taking into account the gender and
      OPT machine seven statistically significant differences were found between the
      appliance groups for the lengths of teeth 31 and 41. Within the groups four teeth
      decreased significantly in length when the pre-adjusted appliance was used (teeth
      12, 11, 21, 26) and four teeth when the Speed appliance was used (teeth 26, 31,
      41, 42). Only tooth 31 was shorter when the Tip-Edge appliance was used. Lower
      incisors were significantly shorter post-treatment if the apices were moved close
      to the lingual cortex. CONCLUSIONS: When panoramic radiographs are used to assess
      treatment-induced changes in the lengths of the incisors, apical resorption is
      only one factor that should be considered. The images of lower incisors proclined
      during treatment may be foreshortened and/or the apices may lie outside the focal
      plane: both may result in 'shorter' teeth post-treatment. Because of the
      confounding factors panoramic radiographs may not be a reliable method of
      determining apical root resorption.

PMID- 17203581
TI  - Comparison of lip positions in ancient Buddhas with Japanese adults.
AB  - OBJECTIVES: To compare the lip positions found in two ancient Buddha statues with
      the lip positions in contemporary Japanese adults. METHODS: The facial profiles
      of Yakushi-ji temple Sho Kannon (male) and Chugu-ji temple Bodhisattva (female),
      generally considered to be two of the most beautiful Buddha statues in existence,
      were compared with the facial profiles of 30 Japanese dental students. Profiles
      of the statues were measured on photographs and profiles of the adults on
      cephalometric radiographs. The adults comprised 15 men between 22 and 26 years of
      age (Mean age: 23.8+/-1.3 years) and 15 women between 22 to 25 years of age (Mean
      age: 22.9+/-1.0 years). RESULTS: The Buddha statues had retrusive lips compared
      with the lip positions in contemporary Japanese adults. CONCLUSION: Flat profiles
      may be favoured by Japanese adults who, typically, have protrusive lips.

PMID- 17203582
TI  - Miniplates and screws in treatment of skeletal Class III malocclusion with
      missing posterior teeth. A case report.
AB  - AIM: To describe the use of miniplates for temporary skeletal anchorage to
      distalise the entire lower dentition. METHODS: A 40 year-old woman presented with
      a skeletal Class III malocclusion and multiple missing maxillary and mandibular
      teeth. The treatment plan was to distalise the mandibular dentition. Two
      miniplates and screws in the mandibular retromolar region were used as temporary
      skeletal anchorage for Class I elastics. The entire lower dentition was
      distalised into a Class I incisor relationship with the miniplate and screw
      anchorage.

PMID- 17203583
TI  - Recognising patterns.

PMID- 17203584
TI  - An interview with Milton Sims.

PMID- 17203585
TI  - Differential expression of glycans in the hippocampus of rats trained on an
      inhibitory learning paradigm.
AB  - The glycan chains of glycoconjugates play important roles in cell-cell and cell
      matrix interactions. In the CNS, previous studies on learning and memory suggest
      the importance of oligosaccharides attached to glycoconjugates in the modulation
      of synaptic connections. We studied the hippocampal glycan distribution of rats
      subject to an inhibitory avoidance task. The expression of glycans was examined
      by lectin-histochemistry using Vicia villosa lectin (VVL) for terminal alpha/beta
      N-acetylgalactosamine (alpha/beta GalNAc); Galanthus nivalus lectin (GNL) for
      terminal mannose alpha-1,3 (Man alpha-1,3); Peanut agglutinin (PNA) for galactose
      beta-1,3N-acetylgalactosamine (Gal beta-1,3 GalNAc); Erythrina cristagalli lectin
      (ECL) for galactose beta-1,4 N-acetylglucosamine (Gal beta-1,4 GlcNAc); Sambucus
      nigra lectin (SNA) for sialic acid alpha-2.6 galactose (SA alpha-2,6 Gal);
      Maackia amurensis lectin II (MAL II) for sialic acid alpha-2,3 (SA alpha-2,3);
      Wheat germ agglutinin (WGA) for terminal N-acetylglucosamine with/ without sialic
      acid (GlcNAc wo SA); succynilated WGA (sWGA) for terminal N-acetylglucosamine
      without sialic acid (terminal GlcNAc without SA); Griffonia simplicifolia lectin
      II (GSL II) for terminal alpha/beta N-acetylglucosamine (alpha/beta GlcNAc
      terminal); and Lotus tetragonolobus lectin (LTL) alpha-fucose. Two groups of 10
      animals were examined: non-trained (Control) and Trained rats. ECL, sWGA and GSL
      II were negative for both groups in all the hippocampal subfields studied. For
      both groups, VVL was negative in CA4 and granular cells of the Dentate Gyrus (DG)
      and LTL was negative in the CA4 subfield. Expression of alpha/beta GalNAc, alpha
      fucose and GlcNAc in other hippocampal subflields was positive, with no
      differences between groups. However, expression of Man alpha-1,3 was
      significantly higher in the CA1, CA2, CA3, and CA4 subfields in the Trained
      group. On the other hand, expression of Gal beta-1,3 GalNAc was significantly low
      in CA4 and DG in the Trained group. In conclusion, the results here presented
      indicate that the exposure of rats to an associative behavioral paradigm related
      to declarative memory, involves some regulatory mechanism/s for the differential
      patterns of glycan expression.

PMID- 17203586
TI  - Quantitative analysis of neurofibrillary pathology in a general population to
      reappraise neuropathological criteria for senile dementia of the neurofibrillary
      tangle type (tangle-only dementia): the Hisayama Study.
AB  - Senile dementia of the neurofibrillary tangle type (SD-NFT) is characterized by
      numerous neurofibrillary tangles (NFT) in the hippocampal region and the absence
      or minimal presence of senile plaques throughout the brain. We analyzed 207
      demented subjects and 68 non-demented subjects autopsied in the Hisayama study to
      investigate the clinicopathological aspects of SD-NFF in the general Japanese
      population. The prevalence of SD-NFT in the consecutive autopsy cases was 8/207
      (3.9%), comprising three men and five women. The average age at onset and death
      was 83.8 +/- 6.8 (mean +/- SD; standard deviation) and 88.1 +/- 7.6 years,
      respectively. A mild memory disturbance preceded a decrease in the ability to
      undertake the activities of daily living and the diagnosis of dementia. Focal
      cerebral symptoms, such as aphasia and paralysis, did not appear during the
      disease course of any subject. Gross examination of the brains showed moderate to
      severe diffuse cerebral atrophy with brain weight loss (mean +/- SD; standard
      deviation: 1118.1 +/- 124.0 g). Histologically, there were abundant NFT and
      neuropil threads predominantly in or limited to the limbic cortex. The density of
      NFT in the CA1/subiculum in SD-NFT was much higher than the densities in the
      other hippocampal regions. The average density of NFT in CA1 in SD-NFT subjects
      was 115.4 per 100 x field (range 23-247), that in Alzheimer disease (AD) subjects
      was 80.1 (range 1-227), and that in non-demented elderly subjects was 37.2 (range
      0-203). Although many previous papers have reported that the densities of NFT in
      the limbic system in SD-NFT were significantly higher than those in AD, there was
      considerable overlap of NFT densities in CA1 among the non-demented elderly, AD
      subjects and SD-NFT subjects.

PMID- 17203587
TI  - Expression of Ki-67, topoisomerase IIalpha and c-MYC in astrocytic tumors:
      correlation with the histopathological grade and proliferative status.
AB  - Astrocytomas represent the most frequent primary tumors of the central nervous
      system. Recently, the determination of the proliferative index of astrocytic
      tumors by different methods has been proposed as a valuable tool for tumor
      grading and also as a prognostic marker. The aim of the present study was to
      evaluate the expression of cell proliferation-related proteins in human
      astrocytic tumors of different histopathological grades (WHO). An
      immunohistochemical study of the Ki-67, Topoisomerase IIalpha (Topo IIalpha) and
      c-MYC proteins using the avidin-biotin-peroxidase method was performed in 55
      astrocytomas (13 grade I, 14 grade II, 7 grade III and 21 grade IV) and five
      samples of non-tumor brain tissue (control group). Ki-67, Topo IIalpha and c-MYC
      positive indices tended to increase according to malignant progression, were
      absent in non-tumor brain tissue and showed maximum values in high-grade
      astrocytomas (III and IV). A gradual increase in Ki-67 antigen expression was
      observed in agreement with mitotic index and histopathological classification.
      The same was not observed for Topo IIalpha and c-MYC. Ki-67 antigen detection in
      more than 8.0% of the tumor cells distinguished astrocytoma grade IV, while a
      labeling index between 1.5 and 8.0% characterized astrocytomas grade III and
      values below 1.5% discriminated low-grade tumors (I and II). These results
      indicate that Topo IIalpha and c-MYC expression is associated with cell
      proliferation in astrocytomas, although not in an exclusive way. Moreover, Ki-67
      antigen was found to be the best marker of cellular proliferation, and its
      expression predicts the grade of astrocytic tumors.

PMID- 17203588
TI  - Locus ceruleus degeneration is ubiquitous in Alzheimer's disease: possible
      implications for diagnosis and treatment.
AB  - Degeneration of the locus ceruleus (LC) and decreased cortical levels of
      norepinephrine are common findings in Alzheimer's disease (AD), but their
      significance is unknown. Because the noradrenergic system is accessible to
      pharmacological intervention, the role of LC degeneration and noradrenergic
      dysfunction in the pathogenesis and clinical manifestations of AD needs
      clarification. Hypothetically, loss of noradrenergic innervation could cause
      microvascular dysfunction and manifest as ischemia. The objectives of this study
      were to develop a scale for assessment of LC degeneration and to determine
      whether degeneration of the LC correlates quantitatively with either duration of
      clinical dementia, overall severity of AD pathology or with measures of ischemic
      non-focal white matter disease (WMD) in AD. This report is a pathological follow
      up of a clinical longitudinal dementia study of 66 consecutive cases of AD
      without admixture of vascular dementia (VaD) from the Lund Longitudinal Dementia
      Study, neuropathologically diagnosed between 1990 and 1999. Ten cases of VaD were
      included for comparative purposes. No correlation between degree of LC
      degeneration and duration of dementia, AD or WMD severity was found. LC
      degeneration was significantly more severe in the AD group than in the VaD group.
      Even though LC degeneration was not associated with WMD or the severity of AD
      pathology in this AD material, we suggest that clinical studies on the
      consequences of noradrenergic dysfunction are warranted. Treatment augmenting
      noradrenergic signaling is available and safe. The marked difference in the level
      of LC degeneration between AD and VaD cases suggests that LC degeneration could
      be used as a diagnostic marker of AD.

PMID- 17203589
TI  - Age-related changes in histogram pattern of anterior horn cells in human cervical
      spinal cord.
AB  - The purpose of the present study was to clarify age-related changes in histograms
      of spinal anterior horn cells. The study examined Rexed lamina IX of the C7
      spinal cord segment in 22 men who had died of non-spinal disease (age range, 0-85
      years). First, we confirmed that the size of nucleoli exhibited a linear
      relationship to the diameter of spinal anterior horn cells by preparing
      histograms of nucleoli. Second, this formula was used to create histograms of
      cervical anterior horn cells. Results were as follows: (i) diameter of nucleoli
      ranged from 2.0 microm to 6.0 microm; (ii) in each subject, no changes were seen
      in histogram patterns among ventral, intermediate, dorsal and overall sections;
      (iii) at < or =20 years of age, histograms displayed a single peak for the
      diameter of nucleoli at about 4.0-4.5 microm; (iv) at 21-60 years of age,
      histograms displayed two peaks, at about 3.5-4.0 microm and 5.0-5.5 microm; and
      (v) at 61-85 years of age, histograms displayed a single peak at about 5.0-5.5
      microm.

PMID- 17203590
TI  - Causes of neuronal heterotopia other than migration disturbances.
AB  - A differentiated form of cerebellocortical fragments (case 1) in the white matter
      or even in the cerebellar dentate nucleus, found in a fetus with trisomy 13, may
      be due to an auto-transplantation accompanied by a penetrating vessel. A similar
      condition was observed in the Ammon's horn (case 2) incidentally as a heterotopic
      tissue fragment of the dentate fascia. Further cause of heterotopia may be
      speculated as a mechanical separation by a surrounding and developing tissue part
      in case of organized, differentiated cerebellocortical heterotopia in the white
      matter (cases 3-5) which were clinically silent. Migration disturbances are not
      the only cause of neuronal heterotopia since the structure of heterotopia is
      differentiated and organized by tissue components.

PMID- 17203591
TI  - Mechanism of cerebral fat embolism in subarachnoid hemorrhage: an experimental
      study.
AB  - Subarachnoid hemorrhage (SAH) may cause neurogenic pulmonary edema (NPE), and
      chylomicron metabolism may be destroyed in injured lungs. We aimed to investigate
      the effect of neurogenic pulmonary edema (NPE), if present, on the development of
      cerebral fat embolism. This study has been conducted on 20 rabbits. Experimental
      SAH has been applied to half of the animals by injecting homologous blood into
      the cisterna magna, and the remaining half was applied only isotonic saline
      solution in the same manner under general anesthesia. After 20 days, all animals
      were killed. Their lungs and brains were examined histopathologically. Six
      animals died of SAH between 16 and 20 days, and foamy hemorrhagic parenchymal
      lesions and intra-alveolar hemorrhage were observed in their lungs. Fat globules
      were abundantly found in cerebral arteries of six of all the non-surviving
      animals. But, minimal histopathological changes were found in the lungs and
      brains of the surviving animals. Cerebral fat embolism was detected in only one
      animal that was given isotonic solution. SAH may cause NPE and result in lung
      tissue destruction. Chylomicron metabolism may be disordered in the destructed
      lungs and leakage of chylomicrons into systemic circulation may be facilitated
      via destroyed lung barrier. These pathologic processes may lead to cerebral fat
      embolism.

PMID- 17203592
TI  - Autopsy case of sporadic Creutzfeldt-Jakob disease presenting with signs
      suggestive of brainstem and spinal cord involvement.
AB  - We describe an autopsy case of MM1-type sporadic Creutzfeldt-Jakob disease (CJD),
      the duration of which was 93 days. The patient was a 59-year-old Japanese man
      with no family history of prion disease or known iatrogenic exposure to CJD. His
      first symptom was dysesthesia in the left arm, suggestive of cervical cord
      involvement, and he showed rapidly progressive neurologic signs, such as
      dysarthria, dysphagia, lethargy, sleep apnea and respiratory failure, suggestive
      of brainstem involvement. Progressive mental deterioration combined with episodes
      of myoclonic seizure and periodic synchronous discharges on the
      electroencephalogram were observed in the later disease stage. Autopsy showed
      typical spongiform change to be wide-spread in the cerebral and cerebellar
      cortices, thalamus and basal ganglia. Synaptic-type PrP deposition was marked in
      the cerebral cortex, thalamus and basal ganglia. In the cerebellum, although the
      granular, molecular and Purkinje cell layers were well preserved from neuronal
      loss and gliosis, PrP deposition was marked in the molecular and granular cell
      layers. Spongiform degeneration and neuronal loss were not seen in the brainstem
      and spinal cord, but relatively marked PrP deposition was observed in the
      quadrigeminal body, substantia nigra, pontine nucleus, inferior olivary nucleus
      and posterior horn. Immunohistochemical staining for HLA-DR showed proliferation
      of activated microglia in the cerebral and cerebellar cortices, pontine nucleus,
      inferior olivary nucleus and posterior horn. The mechanisms underlying the
      neurologic symptoms and signs were unclear, but we speculate that, in addition to
      widespread involvement of the cerebral cortex, PrP deposition and microglial
      activation in the brainstem and spinal cord were responsible.

PMID- 17203593
TI  - Solitary fibrous tumor of the orbit: morphological, cytogenetic and molecular
      features.
AB  - Solitary fibrous tumor (SFT), a benign neoplasm arising in mesenchymal
      structures, was initially described in the pleura but subsequently has also been
      documented in other locations. It is uncommon in the orbit, where it closely
      resembles other benign spindle-shaped mesenchymal tumors of this area such as
      schwannoma, meningioma or hemangiopericytoma. We present a case of orbital SFT in
      a 34-year-old woman. The radiological study showed the presence of an enhanced
      uptake lesion measuring 2 cm in major diameter. The histopathological evaluation
      revealed alternating cellular and hypocellular areas with spindle-shaped cells.
      The cellular organization displayed a broad variety of irregular morphological
      patterns. The neoplastic cells were intensely positive for CD34 and vimentin,
      while S100, epithelial membrane antigen (EMA), Caldesmon, Calretinin and WT-1
      proved negative. The pericellular matrix exhibited strong positivity for CD44 and
      collagen IV. Scarce mitotic figures, a Ki-67 nuclear labeling index of <5%, and
      focal expression of p53 were also observed. Measurement of DNA content revealed a
      DNA index of 1, indicating a diploid peak in 95% of the tumor cells. A normal
      46,XX karyotype was present. No TP53 (exons 5-8) mutations or MDM2 and CDK4
      amplifications were observed. No p14(ARF), p15(INK4B) and p16(INK4A) deletions or
      hypermethylation were observed in this benign tumor. Following surgical resection
      and radiotherapy, the patient showed no tumor relapse after one year of follow
      up.

PMID- 17203594
TI  - Low-grade follicular lymphoma in the dura: rare mimic of meningioma.
AB  - Lymphomas rarely present as a localized mass within the dura. We report a case of
      a 72-year-old woman, normally fit and well, who presented with a sudden episode
      of grand mal seizure. Imaging studies showed an extra-axial mass arising from the
      dura, with radiologic features characteristic of a meningioma. The mass was
      surgically excised, and the histologic features were of a grade 1 follicular
      lymphoma. Analysis using fluorescent in situ hybridization (FISH) demonstrated
      t(14:18) translocation. A bone marrow aspirate showed focal infiltration of
      lumbar vertebra by low-grade follicular lymphoma. Intracranial meningeal
      involvement by non-Hodgkin lymphoma usually occurs in the form of diffuse
      leptomeningeal spread. It is seen in high-grade lymphomas, often in association
      with widespread systemic disease. The majority of cases of dural lymphomas
      reported in the literature have been primary mucosa-associated lymphoid tissue
      (MALT)-type lymphomas. Most of these presented as localized dural masses
      mimicking meningiomas. Low-grade follicular lymphoma, either primary or
      secondarily involving the dura, appears to be an exceedingly rare occurrence.

PMID- 17203595
TI  - Corticobasal degeneration as cause of progressive non-fluent aphasia: clinical,
      radiological and pathological study of an autopsy case.
AB  - A Japanese male developed gradual loss of spontaneous speech at age 60. Three
      years later meaningful speech had deteriorated to the point that it had become
      restricted to monotonous utterances. Neuropsychological examination at age 62
      showed that he had severe non-fluent aphasia. A brain MRI demonstrated mild
      cortical atrophy with ischemic lesions in the cerebral white matter. He was
      diagnosed as having primary progressive aphasia. At age 63, he was admitted to
      the hospital to reevaluate the neurological condition. Neurologic examination
      showed severe non-fluent aphasia, hyperreflexia, snout and sucking reflexes. No
      alien hand was observed. He was able to walk, dress, wash himself and use
      chopsticks as well as name real objects. At age 65, 99Tc-hexamethylpropyleneamine
      oxime single photon emission computed tomography (HMPAO-SPECT) revealed diffuse
      cerebral hypoperfusion that was particularly prominent in the left frontal lobe.
      An MRI showed progressive cortical atrophy with the definite atrophy of the left
      paracentral gyrus. The hippocampal formation and putamen were also atrophic. He
      died of pneumonia at age 67. The brain weighed 810 g with atrophy of the frontal
      lobe, globus pallidus, enlargement of the lateral ventricles and depigmentation
      of the substantia nigra. Microscopic examination showed severe neuronal loss and
      gliosis in the cerebral cortex, globus pallidus interna and substantia nigra.
      Ballooned neurons were observed in the cerebral cortex. Gallyas-Braak method
      revealed numerous astrocytic plaques and argentophilic threads in the cerebrum.
      Clinical diagnosis of corticobasal degeneration sometimes is difficult in
      individuals with atypical clinical presentations. More exact clinical and
      radiological criteria may warrant a diagnosis of corticobasal degeneration.

PMID- 17203596
TI  - Autopsy case of neuro-Behcet's disease with multifocal neutrophilic perivascular
      inflammation.
AB  - We report here an autopsy case of neuro-Behcet's disease. The patient was a 28
      year-old man, who developed a slight fever, right uveitis, and right sensory
      neural hearing loss at the age of 25. These symptoms relapsed repeatedly despite
      treatment. Eventually he was admitted to hospital because of progressing
      neurological deficits such as pyramidal symptoms, somatic sensorial and autonomic
      disorders, and bulbar palsy. The patient's condition deteriorated and he died of
      heart failure. Total clinical course was about three years. In postmortem
      examination, various-sized necrotic foci, often accompanied by gliosis and foamy
      macrophage infiltration, were scattered in the diencephalic region and brain
      stem. Meningitis was observed on the ventral side of the brain stem as well as
      inferior cerebral surface. Nonbacterial or non-fungal acute perivascular
      inflammatory foci were also present in the brain stem and cerebellar parenchyma.
      These histopathological findings suggest that a destructive multifocal
      neutrophilic inflammation might have caused the neurological deficits.
      Perivascular inflammation might be important to understanding the pathogenesis of
      neuro-Behcet's disease.

PMID- 17203597
TI  - Pathological and biochemical studies on a case of Pick disease with severe white
      matter atrophy.
AB  - We report on a male patient with Pick disease who had shown severe white matter
      atrophy and dilatation of the lateral ventricle in the frontal lobe from an early
      stage. Upon admission to our hospital 2 years after disease onset, the patient
      showed apathy, and MRI revealed severe atrophy of the cortex and white matter of
      the frontal lobe. He died at age 74, 11 years after disease onset. Autopsy
      revealed severe atrophy of the frontal and temporal lobes, severe loss of white
      matter in the frontal lobe, dilatation of the lateral ventricles, and cortical
      thinning. Histopathological examination showed severe loss of myelinated fibers
      in the frontal white matter and severe neuronal loss with gliosis in the frontal
      and temporal cortices. Many Pick bodies were seen. Our patient had a rare case of
      Pick disease predominantly affecting the frontal lobe with severe involvement of
      the white matter from an early stage. This case suggests that myelinated fibers
      in the white matter as well as cerebral neurons are primarily affected in Pick
      disease.

PMID- 17203598
TI  - A 52-year-old man with hypohidrosis.

PMID- 17203599
TI  - Coupling of the biochemical composition and calorific content of zooplankters
      with the Microcystis aeruginosa proliferation in a highly eutrophic reservoir.
AB  - The impact of the Cyanobacteria Microcystis aeruginosa on zooplankton dynamics
      was studied in the hypertrophic Villerest Reservoir (France). Samples were
      collected and their biochemical composition and calorific content examined. Three
      most abundant zooplankton species in the reservoir were considered: the
      cladoceran Daphnia longispina and the copepods Cyclops vicinus and Eudiaptomus
      gracilis. The three species were differently affected by the Microcystis
      aeruginosa blooms. Daphnia longispina did not seem to suffer from the
      proliferation of the M. acruginosa, although its biomass decreased concomitantly
      to the bloom. This collapse would be attributable to the lack of nutritional
      value of algae. Cyclops vicinus seemed to move away when Microcystis invaded the
      superficial layers of the reservoir. Because this zooplankter had migratory
      abilities, it reached the littoral zone where food was available. The energetic
      costs linked to this migration were clearly pointed out when the species
      recovered the pelagial zone in early fall. The behaviour of Eudiaptomus gracilis
      was not clear. This species underwent diapause as M. aeruginosa proliferated.
      This suggests that Eudiaptomnus gracilis moved away from the pelagial zone over
      the cyanobacterial blooms. In most cases, the cyanobacterial toxins affected the
      growth of zooplankton and the potential to use herbivorous zooplankton as a means
      to combat Microcystis proliferation in the Villerest reservoir seems limited.

PMID- 17203600
TI  - Photocatalytic degradation of 2,4-dichlorophenoxyacetic acid and 4-chloro-2
      methylphenoxyacetic acid in water by using TiO2.
AB  - The photocatalytic degradation of many chlorinated organic compounds by
      semiconductor particles, has been widely recognised as a promising method of
      water and wastewater treatment process. In the present work the photocatalytic
      transformation of 2,4-D and MCPA in aqueous solution with 2 g l(-1) suspended
      TiO2 is demonstrated. The formation of several intermediates has been observed.
      The photodegradation rate increases with increasing pH. The photocatalytic
      transformation of 2,4-D and MCPA over TiO2 in solution containing hydrogen
      peroxide has been also studied. H2O, accelerated significantly the reaction rate
      of 2, 4-D and MCPA. The partial inhibition by ethanol is attributed to the
      scavenging of OH radicals involved in the first step of the reaction. Finally,
      from these results, a mechanism is proposed. This photocatalytic method has good
      potential for application on a large scale.

PMID- 17203601
TI  - Improvement of aquaculture wastewater using chitosan of different degrees of
      deacetylation.
AB  - Removal of organic compounds and inorganic nutrients from aquaculture wastewaters
      prior to discharge can not only minimize deterioration of receiving water
      quality, but it could also be further reused to culture prawn, fish and
      shellfish. Chitosan can be used as a coagulant, adsorbent, or bactericide;
      therefore it has been used to improve aquaculture wastewater quality as it could
      remove suspended solids (SS), organic compounds, NH3, PO43-, and pathogens. The
      best performance of chitosan in removing turbidity, SS, chemical oxygen demand
      (COD), NH3, and PO43- was 90%, 61%, 69.7%, 89.2%, and 95.6%, respectively. In
      addition, the chitosan could selectively remove the pathogen Edwardsiella
      ictaluri while leaving beneficial nitrifying bacteria in the aquaculture
      wastewater unaffected. The treatment efficiency of chitosan was highly dependent
      on its deacetylation degree and the pH of the wastewater. A high deacetylation
      degree and low pH value improved the performance of chitosan. In summary, the
      multi-functional chitosan deserves a wider role in treating aquaculture
      wastewater.

PMID- 17203602
TI  - Tyrosinase extract from Agaricus bisporus mushroom and its in natura tissue for
      specific phenol removal.
AB  - Phenols are toxic pollutants found in industrial wastes imposing several risks to
      human health. Tyrosinase (EC 1.14.18.1) is an oxygenase oxyreductase found in
      several life forms, like the mushroom Agaricus bisporus. This enzyme is readily
      available from this fungal tissue leading to high activity extracts without
      extensive purification, thus suggesting its potential as a biocatalyst for
      applications involving biomodification of phenols or bioremediation of phenol
      polluted waters. The purpose of this work was to employ a crude extract from the
      Agaricus bisporus mushroom and its biomass for the removal of phenol from
      polluted water. Experiments were carried out without pH control. The initial
      phenol concentration in all solutions was 100 mg l(-1). Four enzymatic
      concentrations (50, 100, 200 and 400 U ml(-1)) were tested. Reactions, with 200 U
      ml(-1) and 400 U ml(-1) enzymatic activity, led to 90% of phenol removal.
      Chitosan was used as a coagulant, but no significant improvement was observed.
      The in natura fungi was also able to remove 90% of phenol, demostrating its
      viability as a biocatalyst in bioremediation process.

PMID- 17203603
TI  - The stability of hydrated aluminium phosphate, AlPO4 x 1.5H2O.
AB  - The dissolution mechanism and stability of a synthetic hydrated aluminium
      phosphate, AlPO4 x 1.5H20 (AlPO4-H3) was investigated at 22 degrees C over the pH
      range 2.4 to 8.8. AlPO4 x 1.5H2O was found to be more soluble than the better
      known dihydrate (variscite, AIPO4 x 2H2O) hence proving to be metastable. This
      material was determined to undergo incongruent dissolution at pH around 3.0 and
      higher producing initially amorphous Al(OH)3 which gradually (within 30-day
      dissolution period) converted to the stable gibbsite phase. Upon evaluation of
      the experimental data with PHREEQC it was possible to calculate the solubility
      product ( logKsp ) and the standard Gibbs free energy of formation (deltaGf,0)
      for AlPO4 x 1.5H2O to be respectively-- 20.46+/-0.40 and -1980.5+/-.0 kJ mol(-1)
      at 22 degrees C.

PMID- 17203604
TI  - Waste lime as a potential cation source in the phosphate crystallization process.
AB  - In this study, the feasibility of waste lime as a potential cation source in
      phosphate crystallization process was investigated using laboratory scale up flow
      reactors, adopting sequencing batch type configuration. This research focused on
      its successful application in a novel sludge treatment process, which is
      comprised of a high performance fermenter (operating conditions: 55 degree C and
      pH 9) followed by a crystallization reactor. In the struvite precipitation test
      using synthetic wastewater, considerable nutrient removal (about 60%) in the form
      of ammonia and phosphate was observed within 0.5-1 hr of retention time, and only
      small amounts (< 5%) of ammonia stripping occurred naturally due to the alkaline
      (pH 9) characteristic of the feed substrate. By replacing the synthetic
      wastewater with the fermentation effluent, the optimal dosage of magnesium salt
      for struvite precipitation was 0.86 g Mg g(-1) P, similar to the mass ratio of
      the struvite. The optimal dosage of waste lime was 0.3 g 1(-1), resulting in 80 %
      of NH4-N and 41% of PO3-P removal, at about 3 hrs of retention time. Microscopic
      analysis showed that amorphous crystals were mainly observed in the settled
      solids with waste lime addition whereas prism-like crystals were found in the
      system with magnesium salt added. Mass balance analysis in full-scale model
      plants (Q=158,880 m(3)d(-1)) based on the present experimental results revealed
      that nutrient recycle loading from side stream to main liquid stream would be
      significantly reduced. The results of the experiment reveal that reuse of
      industrial waste lime in a nutrient recovery system has the various advantages
      such as higher economical benefits and sustainable treatment of the industrial
      waste.

PMID- 17203605
TI  - Estimation on the self recovery behavior of low-conductivity layer in landfill
      final cover by laboratory conductivity tests.
AB  - This study examined the application of a Self Recovering Sustainable Layer (SRSL)
      as a landfill final cover. Low-conductivity layers in landfill covers are known
      to have problems associated with cracking as a result of the differential
      settlement or climatic changes. A SRSL is defined as a layer with chemical
      properties that reduces the increased hydraulic conductivity resulting from
      cracking by forming low-conductivity precipitates of chemicals contained in the
      layer. In this study, the formation of precipitates was confirmed using a batch
      test, spectroscopic analysis and mineralogical speciation tests. The possibility
      of secondary contamination due to the chemicals used for recovery was evaluated
      using a leaching test. A laboratory conductivity test was performed on a single
      layer composed of each chemical as well as on a 2-layer system. The recovery
      performance of the SRSL was estimated by developing artificial cracks in the
      specimens and observing the change in hydraulic conductivity as a function of
      time. In the laboratory conductivity test, the hydraulic conductivity of a 2
      layer system as well as those of the individual layers that comprise the 2-layer
      system was estimated. In addition sodium ash was found to enhance the reduction
      in conductivity. A significant increase in conductivity was observed after the
      cracks developed but this was reduced with time, which indicated that the SRSL
      has a proper recovering performance. In conclusion, a SRSL can be used as a
      landfill final cover that could maintain low-conductivity even after the serious
      damages due to settlement.

PMID- 17203606
TI  - Determination of denitrifying sludge settleability using contact angle
      measurements.
AB  - The adaptation of the technique for measuring the contact angle (CA) in order to
      follow the changes of sludge settleability of a denitrifying sludge surface is
      described. Denitrifying sludge was continuously fed into an upflow anaerobic
      sludge blanket (UASB) reactor with acetate and nitrate. The loss of settleability
      in the sludge was induced by decreasing the hydraulic residence time (HRT) from 1
      d to 0.125 d. CA was measured with air and nitrogen bubbles. A comparison between
      sludge volume index (SVI) and the CA and their correlation with sludge
      settleability was carried out. Results showed that CA method had a high
      correlation with sludge settleability. Moreover the CA method showed to be
      simpler and less time consuming than the SVI method.

PMID- 17203607
TI  - The bacteria in the sediment of the Sahela reservoir (Morocco): potential impacts
      on phosphorus budget.
AB  - Temporal variations of phosphorus concentrations, bacterial abundance and
      activity of fractionated (i.e: size fractions: 0.22 to 0.65 microm; 0.65 to 100
      microm and 0.22 to 100 microm) alkaline phosphatase (APA) were studied in situ in
      a benthic chamber placed in a station near urban inputs in the Sahela reservoir
      (Morocco) on September and October 98. Results show that low oxygen
      concentrations induced enhanced concentrations of orthophosphates, and bacterial
      numbers and APA activity reached their highest values. Anoxic conditions and the
      decrease of pH favour the dissolution of particulate phosphorus and the release
      of soluble reactive phosphorus. This release is accompanied simultaneously by an
      increase in the abundance of anaerobic bacteria and a progressive reduction in
      APA. Lastly, the release of phosphorus together with urban inputs from the city
      of Taounate should be considered as potential inducers of the eutrophication of
      the reservoir.

PMID- 17203608
TI  - A preliminary investigation on boron and metal concentrations of the main
      drainage channel in Konya-Turkey.
AB  - In this work, the wastewaters and sediments of the main drainage channel in Konya
      (Turkey) were collected from three different sampling points and analyzed for
      metals, including iron, chromium, copper, lead, zinc and nickel by using
      inductively coupled plasma-atomic emission spectrometry (ICP-AES). It was found
      that for all sampling points sediment samples show a decrease in concentrations
      in the order Fe >> Zn > Cr > Ni > Cu > Pb. For all sampling points, heavy metal
      concentrations in wastewater did not exceed the maximum admissible discharge
      levels regulated by the Institute of Turkish Standards. However, it was found
      that boron concentration of wastewaters exceed the safe level for irrigation of
      farmland.

PMID- 17203609
TI  - UV inactivation of bacteria in raw and pretreated liquid swine manure.
AB  - The study was conducted to investigate the effectiveness of ultraviolet (UV)
      irradiation for inactivating coliform bacterial indicators in liquid swine manure
      samples using a laboratory-scale, low-pressure UV collimated beam apparatus. Raw
      liquid swine manure was brought from the field and stored at 4 'C for preliminary
      settling for 24 hours, which was followed by alum treatment in a jar test
      apparatus. Both pre-settled and alum-treated supernatants were filtered
      separately through different pore-sized polycarbonate membrane filters. The
      unfiltered and filtered pre-settled and alum-treated supernatant samples were
      exposed to a range of UV fluences (i.e., doses) to determine the fluence-response
      relationship. After preliminary settling, alum treatment, and membrane
      filtration, UV absorbance values of undiluted swine manure samples at 254 nm
      varied between 4.0 and 4.2 cm(-1) with total suspended solids concentrations of
      800 to 1,800 mg l(-1). Total coliforms were reduced by 2 - to 2.5-log10 at UV
      fluences of 80 to 100 mJ cm(-2). Relatively small log reductions (< 0.5-log10)
      were observed at lower fluences (below 20 mJ cm(-2) ) in undiluted manure
      samples. To reduce the UV absorbance of liquid swine manure, raw manure was
      diluted 1:50 and 1:10 with deionized water in subsequent experiments. Almost
      complete inactivation (> 4 to 5 log10) was achieved at UV fluences of 20 mJ cm(
      2) or higher in the swine manure samples diluted to 1:50. Based on these
      findings, it was proposed that UV inactivation of coliform in the undiluted
      liquid swine manure was limited by association of bacterial cells with
      particulate matter of less than 10 microm in size. Dilution may have disrupted
      and reduced the association between the bacteria and this fine particulate matter
      resulting in better dispersion and more complete inactivation by UV.

PMID- 17203610
TI  - Development of a novel monolith-bioreactor for the treatment of VOC-polluted air.
AB  - A novel bioreactor packed with ceramic monolith colonized by a toluene-degrading
      culture was investigated in order to assess its suitability for waste gas
      treatment. Operational parameters that were considered included start-up of the
      bioreactor, toluene loading rate, changes in gas flow rate, liquid feed mode, and
      steady-state operation. This is the first report on the treatment of toluene
      polluted air in such a biological monolith reactor. Data on performance and
      stability have been obtained showing that this system is suitable for waste gas
      treatment. Removal efficiencies around 90% could be maintained at different gas
      flow rates, although this value gradually dropped when increasing the load above
      30 g m(-3) h(-1). Interestingly, omitting the continuous feed of a liquid
      trickling phase improved the reactor's performance. One potential drawback that
      needs to be minimized is related to clogging after long term operation. Further
      studies aimed at optimizing this novel application would allow reaching a high
      performance under long-term, stable conditions.

PMID- 17203611
TI  - An exemple of particle concentration reduction in Parisian subway stations by
      electrostatic precipitation.
AB  - The air quality in Parisian subway stations is a great concern to users and the
      public authorities. Particle concentration is one of the major problems; indeed
      concentrations observed in stations are generally superior to those collected in
      the street. The subway generates its own particles from wheels / rail contact,
      braking, the ground... One of the ways explored to lower this level of particles
      is a removal treatment: the principle is to treat the ambient air using a
      suitable system placed in stations. Following literature, the process chosen by
      Paris Transport Authority is the electrostatic precipitator. An electrostatic
      precipitator prototype from the Recycl'Air company is installed in May 2001 in a
      closed station on the 5th line (Italy Place -Bobigny). Results show that, by the
      end of approximately one year, the efficiency has fallen by 15% and it is
      therefore necessary to clean the precipitation cartridges. A consideration has
      also been made on the possibility to equip an entire subway station. According to
      the results obtained, about twenty filters placed in the top of a non
      mechanically ventilated station would permit to half an initial concentration in
      particles of 230 microg m(-3).

PMID- 17203612
TI  - Effect of electrochemical treatment of oleic acid on anaerobic digestion.
AB  - Electrochemical pre-treatment of oleate on anaerobic digestion was investigated
      using two anaerobic filters (AF and AFm) working, respectively, with increasing
      concentrations of electrochemically pre-treated oleate and oleate. Influents
      containing 25% and 50% of chemical oxygen demand (COD) of these substrates did
      not cause relevant alterations in either digester's performance. Comparatively,
      the pre-treated oleate unit (AF) showed a higher gas production but a lower COD
      removal than AFm (2.0 vs 1.5 m(3) CH4 m(-3) d(-1) 76-85 vs 91-93% COD removal).
      The raised AFm COD removal together with the larger proportion of VSS in its
      effluent than in AF (5.69 vs 0.26 kg m(-3)) indicate that the biomass washout can
      be a consequence of the encapsulated solids by lipidic compounds that were not
      fairly degraded. Further increases of oleate in AFm feed (75 and 100% COD) led to
      decreases of biogas production to half and COD removal from values higher than
      90% to 83-75%. The simultaneous increase of effluent VSS concentrations to 10-12
      kg m(3) emphasizes the oleate negative effect. The use of pretreated oleate as
      the only carbon source did not influence negatively the AF behaviour in terms of
      methane production. COD removal was maintained at values higher than 80% and the
      effluent VSS at low concentrations (0.15 kg m(-3)). The significantly higher
      methane yield achieved by AF than AFm indicates a higher accumulation of oleate
      than pre-treated oleate. Therefore, electrochemical process stands for a suitable
      pre-treatment for lipid rich effluents, allowing the application of higher
      organic loads keeping a higher methane yield.

PMID- 17203613
TI  - Urbanicity and schizophrenia. From statistical association to causality?

PMID- 17203614
TI  - Urban birth and risk of schizophrenia: a worrying example of epidemiology where
      the data are stronger than the hypotheses.
AB  - There is robust and consistent evidence from epidemiological studies showing that
      urban birth is associated with an increased risk of developing schizophrenia.
      Evidence suggests that this exposure may be associated with a sizeable proportion
      of cases. To date the candidate exposures underlying the urban birth risk factor
      have included infectious agents, low prenatal vitamin D, toxins associated with
      pollution, and stress. However, in general, the hypotheses proposed to explain
      the urban birth risk factor have been unsatisfying. In light of the general trend
      towards increasing urbanization, it is feasible that the attributable fraction of
      schizophrenia associated with urban birth may increase. The psychiatric research
      community should have a sense of urgency in exploring the mechanisms linking
      urban birth and risk of schizophrenia.

PMID- 17203615
TI  - Why factors rooted in the family may solely explain the urban-rural differences
      in schizophrenia risk estimates.
AB  - Many studies have identified urban-rural differences in schizophrenia risk. The
      underlying cause(s) may hypothetically include toxic exposures, diet, infections,
      and selective migration. In a recent study, we concluded that some of the
      cause(s) responsible for the urban-rural differences in schizophrenia risk are
      rooted in families, but some might also be rooted in individuals. First, we
      describe temporality as a potential methodological pitfall within this line of
      research, then we review studies not subject to this pitfall, and finally, we
      describe why factors rooted in the family may solely explain the urban-rural
      differences. Although other potential explanations for these differences exist,
      we focus on this hypothesis as it has not previously been discussed in detail. To
      determine the cause(s) responsible for the urban-rural differences, we need
      direct measurements of genetic and/or environmental factors related to urban
      life.

PMID- 17203616
TI  - The psychosis proneness: psychosis persistence model as an explanation for the
      association between urbanicity and psychosis.
AB  - Given the relatively high attributable risks associated with urbanicity it is
      crucially important to learn more on how this exposure impacts on population risk
      for schizophrenia. Further elucidation of the environmental influences that
      currently go under the name of "urbanicity" therefore is a crucial step in
      unravelling the etiology of schizophrenia. In order to make the step from
      association to cause, a plausible mechanism detailing the pathway from impact of
      exposure to onset of psychotic symptoms is needed. This paper outlines possible
      avenues and clues to the identification of possible mechanisms and pathways. The
      focus is on mechanisms of gene-environment interaction in the context of both
      functional genetic polymorphisms and epigenetic variation.

PMID- 17203617
TI  - What is a forest plot?

PMID- 17203618
TI  - Equity in mental health.
AB  - AIM: The aim of this paper is to discuss the study of equity in mental health
      contexts. METHODS: We review major principles and theories of distributive
      justice, covering various disciplines such as ethics, philosophy, economics,
      medicine and sociology. Recent literature on empirical analysis of inequalities
      in the mental health field is also reviewed. RESULTS: The review of literature
      reveals a general lack of debate on equity principles in relation to mental
      health. Robust empirical evidence on inequalities in the field is also scarce.
      CONCLUSIONS: There is need for better exposition of the relevance of different
      equity principles for mental health policy and practice. There is also a need for
      developing standardised methods for the empirical analysis of equity, to examine
      the distribution of psychiatric morbidity and use of services by income, socio
      economic group, ethnicity, gender and place of residence, and, of course, to
      examine how equity can be promoted.

PMID- 17203619
TI  - Cognitive behaviour therapy for psychosis.
AB  - AIMS: It used to be thought that the problems of psychosis were qualitatively
      difference from those of other disorders and therefore unamenable to
      psychological interventions. However more recent evidence will be summarised
      which suggests otherwise. METHODS: A cognitive model of the positive symptoms of
      psychosis (Garety et al., 2001; Kuipers et al., 2006) is described which builds
      on work on the dimensions of symptoms of psychosis, the continuum between non
      clinical and clinical populations, and the contribution of emotional processes,
      cognitive reasoning biases and social factors. RESULTS: Evidence from both
      epidemiological and empirical studies from our research group and others, support
      some of the pathways of symptom formation and maintenance proposed by the model.
      Specifically there is evidence for the role of trauma, social adversity and
      stress. These may trigger emotional responses and unusual experiences and
      together with reasoning biases lead to appraisals that can be defined as positive
      symptoms such as delusions and hallucinations. Similar processes interact to
      maintain symptoms. CONCLUSIONS: Cognitive models of psychosis have led to the
      development of cognitive behavioural treatments for delusions and hallucinations,
      which show some evidence of efficacy. Such treatments need to be refined in the
      light of recent research.

PMID- 17203620
TI  - Identification and management of depression in primary care settings. A meta
      review of evidence.
AB  - AIM: The purpose of this review is to summarize the evidence base on the
      effectiveness of (a) screening for depression in primary care; (b) managing
      depression in primary care employing specific management strategies; (c) treating
      primary care depressive patients with antidepressants. METHODS: Meta-review of
      all available reviews of the evidence. RESULTS: Screening alone does not improve
      the recognition, management and outcome of depression in primary care settings.
      Management strategies, including (a) training primary care staff, (b)
      consultation-liaison, (c) collaborative care, (d) replacement/referral are
      supported by insufficient evidence to provide a definite answer as to the
      clinical effectiveness of individual models. Robust evidence exists to encourage
      physicians to prescribe effective doses of antidepressants in patients with
      moderate to severe depression who seek treatment in primary care settings.
      CONCLUSION: Population-level screening campaigns have a negative ratio of costs
      to benefits. However, at an individual-level of care increasing the ability of
      primary care physicians in recognising depression remains a relevant factor.
      Primary care physicians should consider whether depression is mild, moderate or
      severe. This patient categorisation help develop appropriate management and
      therapeutic strategies.

PMID- 17203621
TI  - [Depression and stroke: an up-to-date review].
AB  - AIMS: To define the epidemiological and clinical characteristics of Post Stroke
      Depression (PSD) and to evaluate treatment options. METHODS: Systematic search
      using Medline electronic database limited to studies published from year 2000 to
      2004, was carried out. Manual search was also performed. RESULTS: Depression
      after stroke is a common event. The same, stroke incidence in depressed patients
      is more frequent than by chance. Risk of underdiagnosing a patient with former
      stroke is high. Disability after stroke is frequent, with compromission of
      quality of life of patients and relatives. Antidepressants are efficacious in PSD
      treatment, even if complete remission is difficult to obtain. CONCLUSIONS: There
      is enough evidence concerning epidemiology, pathogenesis, clinical and therapy to
      justify psychiatrists' interest on relationship between stroke and depression.

PMID- 17203622
TI  - [Proposal for a new funding system for mental health departments. Results from an
      evaluative multicentre Italian study (I-psycost)].
AB  - AIMS: To obtain a new, well-balanced mental health funding system, through the
      creation of (i) a list of psychiatric interventions provided by Italian Community
      based Psychiatric Services (CPS), and associated costs; (ii) a new prospective
      funding system for patients with a high use of resources, based on packages of
      care. METHODS: Five Italian Community-based Psychiatric Services collected data
      from 1250 patients during October 2002. Socio-demographical and clinical
      characteristics and GAF scores were collected at baseline. All psychiatric
      contacts during the following six months were registered and categorised into 24
      service contact types. Using elasticity equation and contact characteristics, we
      estimate the costs of care. Cluster analysis techniques identified packages of
      care. Logistic regression defined predictive variables of high use patients.
      Multinomial Logistic Model assigned each patient to a package of care. RESULTS:
      The sample's socio-demographic characteristics are similar, but variations exist
      between the different CPS. Patients were then divided into two groups, and the
      group with the highest use of resources was divided into three smaller groups,
      based on number and type of services provided. CONCLUSIONS: Our findings show how
      is possible to develop a cost predictive model to assign patients with a high use
      of resources to a group that can provide the right level of care. For these
      patients it might be possible to apply a prospective per-capita funding system
      based on packages of care.

PMID- 17203623
TI  - Burnout syndrome of general practitioners in post-war period.

PMID- 17203624
TI  - [A comparison of community living versus non-hospital residential facilities
      chronic schizophrenics].

PMID- 17203625
TI  - Joanna Hirst.

PMID- 17203626
TI  - A duty to care: ending discrimination.

PMID- 17203627
TI  - Bringing the bedside to the boardroom, and the boardroom to the bedside.

PMID- 17203628
TI  - Good care is good business.

PMID- 17203629
TI  - Innovation and improvement.

PMID- 17203630
TI  - Ten steps to effective delegation.

PMID- 17203631
TI  - Global thinking.

PMID- 17203632
TI  - Ensuring fitness for practice.

PMID- 17203633
TI  - Promoting public health: Part 2.

PMID- 17203634
TI  - Key attributes of health ministries in African American churches: an exploratory
      survey.
AB  - BACKGROUND: Church leaders are considered instrumental in the successful
      implementation of church-based health programs. However it is unknown which
      program attributes they perceive as important and which program attributes exist
      in their congregations. OBJECTIVE: To explore the perceived importance and
      existence of health ministry-related attributes in predominately African American
      churches. METHODS: Cross-sectional survey, with a convenience sample of 98
      registered church leaders attending a conference on health and spirituality in
      Raleigh, NC. Attendees were asked to complete a brief survey assessing perceived
      importance (very important vs. somewhat or not important) and existence (yes vs.
      no) of 20, health ministry-related attributes in their churches. Percent
      perceived as very important, percent existence, and their differences were
      assessed for each attribute. RESULTS: Seventy-two (73.5%) of the attendees
      completed the survey. Attributes perceived as very important were: displaying
      health information in churches (73.6%); hosting health fairs for church members
      (73.2%); pastoral, church-based Internet access (70.8%); willingness to receive
      foundation funding for activities (66.7%); and incorporating health messages in
      Sunday bulletins (65.3%). For each of these program attributes, there was a gap
      between the proportion rating them "very important" and existence of the
      attribute in their own congregations (range diff in %: -8.3 to -22.2).
      LIMITATIONS: Lack of generalizability due to sample selection and homogeneity.
      CONCLUSIONS: Among leaders surveyed, despite perceived importance, attributes did
      not exist for all. Future studies should evaluate whether attributes considered
      important by church leadership parallel an increase in the development and
      maintenance of health program activities, and are associated with congregation
      health behaviors and health outcomes.

PMID- 17203635
TI  - Sexually transmitted diseases: will this problem ever go away?

PMID- 17203636
TI  - Current and best practices for testing of sexually transmitted diseases.

PMID- 17203637
TI  - Public health approaches to North Carolina's STD epidemic.

PMID- 17203638
TI  - Responding with treatment to those acutely infected with HIV: no time to lose.

PMID- 17203639
TI  - Responding to the epidemic of STDs through public education and community
      intervention.

PMID- 17203640
TI  - Opportunities for addressing the STD epidemic through interventions targeted to
      North Carolina's incarcerated populations.

PMID- 17203641
TI  - Guilford County's syphilis elimination program: People Stopping Syphilis Today
      (PSST).

PMID- 17203642
TI  - Syphilis elimination in Robeson County: challenges of addressing the problem
      among sex workers.

PMID- 17203643
TI  - A vaccine for genital HPV: a time to rejoice!

PMID- 17203644
TI  - What North Carolinians can expect from the healthcare system: eleven things
      learned during a "special" month of residency training.

PMID- 17203645
TI  - One of North Carolina's largest philanthropies supports and listens to HIV/AIDS
      service providers.

PMID- 17203646
TI  - Interpretation of sexually transmitted disease surveillance data.

PMID- 17203647
TI  - Rapid response teams in North Carolina hospitals.

PMID- 17203648
TI  - Attitude, actions and service at a "public" hospital.

PMID- 17203649
TI  - Conditional somatic mutagenesis in the mouse using site-specific recombinases.
AB  - In the last decade, site-specific recombinases (SSRs), such as Cre and Flp, have
      emerged as indispensable tools for the precise in vivo manipulation of the mouse
      genome. It is now feasible to control, in space and time, the onset of gene
      knockouts in almost any tissue of the mouse, thus greatly facilitating the
      creation of sophisticated animal models for human disease and drug development.
      This review describes the basic principles and current status of the SSR
      technology, with a focus on strategies for conditional somatic mutagenesis using
      the Cre/lox system and ligand-activated Cre recombinases. Practical hints for
      generating and analysing conditional mouse mutants will be given and exciting
      novel applications of the SSR technology will be discussed, such as cell fate
      mapping and the combined use of Cre, Flp and other biotechnological tools. It
      will be shown how genetic manipulation of the mouse by site-specific
      recombination can provide new solutions to old problems in the analysis of human
      physiology and pathophysiology and how it can be employed for drug discovery and
      development.

PMID- 17203650
TI  - Cre/loxP-mediated chromosome engineering of the mouse genome.
AB  - Together with numerous other genome modifications, chromosome engineering offers
      a very powerful tool to accelerate the functional analysis of the mammalian
      genome. The technology, based on the Cre/loxP system, is used more and more in
      the scientific community in order to generate new chromosomes carrying deletions,
      duplications, inversions and translocations in targeted regions of interest. In
      this review, we will present the basic principle of the technique either in vivo
      or in vitro and we will briefly describe some applications to provide highly
      valuable genetic tools, to decipher the mammalian genome organisation and to
      analyze human diseases in the mouse.

PMID- 17203651
TI  - Tetracycline-controlled genetic switches.
AB  - Unlike recombinase-mediated gene manipulations, tetracycline (Tet)-controlled
      genetic switches permit reversible control of gene expression in the mouse.
      Trancriptional activation can be induced by activators termed tTA (Tet-Off) or
      rtTA (Tet-On) in the absence and presence of Tet, respectively. The Tet-Off and
      Tet-On systems are complementary, and the decision to choose one over the other
      depends on the particular experimental strategy. Both systems were optimized over
      the years and can now be used to develop mouse models.

PMID- 17203652
TI  - Novel gene switches.
AB  - Controlling gene activity in space and time represents a cornerstone technology
      in gene and cell therapeutic applications, bioengineering, drug discovery as well
      as fundamental and applied research. This chapter provides a comprehensive
      overview of the different approaches for regulating gene activity and product
      protein formation at different biosynthetic levels, from genomic rearrangements
      over transcription and translation control to strategies for engineering
      inducible secretion and protein activity with a focus on the development during
      the past 2 years. Recent advances in designing second-generation gene switches,
      based on novel inducer administration routes (gas phase) as well as on the
      combination of heterologous switches with endogenous signals, will be
      complemented by an overview of the emerging field of mammalian synthetic biology,
      which enables the design of complex synthetic and semisynthetic gene networks.
      This article will conclude with an overview of how the different gene switches
      have been applied in gene therapy studies, bioengineering and drug discovery.

PMID- 17203653
TI  - Improved embryonic stem cell technologies.
AB  - Murine embryonic stem (ES) cells have become an indispensable tool for
      investigating genetic function both in vitro and, importantly, in vivo. Recent
      advances, including tetraploid aggregation, new site-specific recombinases and
      RNAi, have enabled more sophisticated manipulation of the ES cell genome. For
      instance, it is now possible to control gene expression in both a temporally and
      spatially restricted manner. Such new technologies are answering complex
      questions surrounding the function and interaction of an increasing number of
      genes. This chapter will review both the history and recent technological
      progress that has been made in mouse ES cell derivation, genetic manipulation and
      the generation of ES cell-derived chimaeric animals.

PMID- 17203654
TI  - Gene trap mutagenesis.
AB  - Our ability to genetically manipulate the mouse has had a great impact on medical
      research over the last few decades. Mouse genetics has developed into a powerful
      tool for dissecting the genetic causes of human disease and identifying potential
      targets for pharmaceutical intervention. With the recent sequencing of the human
      and mouse genomes, a large number of novel genes have been identified whose
      function in normal and disease physiology remains largely unknown. Government
      sponsored multinational efforts are underway to analyze the function of all mouse
      genes through mutagenesis and phenotyping, making the mouse the interpreter of
      the human genome. A number of technologies are available for the generation of
      mutant mice, including gene targeting, gene trapping and transposon, chemical or
      radiation-induced mutagenesis. In this chapter, we review the current status of
      gene trapping technology, including its applicability to conditional mutagenesis.

PMID- 17203655
TI  - RNA interference in mice.
AB  - Silencing of gene expression by RNA interference (RNAi) has become a powerful
      tool for functional genomics in mammalian cells. Furthermore, RNAi holds promise
      as a simple, fast and cost-effective approach to studying mammalian gene function
      in vivo and as a novel therapeutic approach. This review provides an overview of
      the progress of RNAi in vivo, with emphasis on systemic/local siRNA delivery,
      viral shRNA vectors, shRNA vector transgenic mice and conditional systems to
      control shRNA vectors. Taken together, the data from 80 in vivo studies show that
      RNAi is a useful tool that offers new opportunities for functional genomics in
      mice.

PMID- 17203656
TI  - Viral vectors: a wide range of choices and high levels of service.
AB  - Viruses are intracellular parasites with simple DNA or RNA genomes. Virus life
      revolves around three steps: infection of a host cell, replication of its genome
      within the host cell environment, and formation of new virions; this process is
      often but not always associated with pathogenic effects against the host
      organism. Since the mid-1980s, the main goal of viral vectorology has been to
      develop recombinant viral vectors for long-term gene delivery to mammalian cells,
      with minimal associated toxicity. Today, several viral vector systems are close
      to achieving this aim, providing stable transgenic expression in many different
      cell types and tissues. Here we review application characteristics of four vector
      systems, derived from adeno-associated viruses, adenoviruses, retroviruses and
      herpes simplex virus-1, for in vivo gene delivery. We discuss the transfer
      capacity of the expression vectors, the stability of their transgenic expression,
      the tropism of the recombinant viruses, the likelihood of induction of
      immunotoxicity, and the ease (or difficulty) of the virus production. In the end,
      we discuss applications of these vectors for delivery of three molecular systems
      for conditional mutagenesis, two for inducible transcriptional control of
      transgenic expression (the tet and the dimerizer systems), and the third one for
      inducible control of endogenous gene expression based on RNA interference.

PMID- 17203657
TI  - Conditional mutagenesis by cell-permeable proteins: potential, limitations and
      prospects.
AB  - The combination of two powerful technologies, the Cre/loxP recombination system
      and the protein transduction technique, holds great promise for the advancement
      of biomedical and genome research by enabling precise and rapid control over
      mutation events. Protein transduction is a recently developed technology to
      deliver biologically active proteins directly into mammalian cells. It involves
      the generation of fusion proteins consisting of the cargo molecule to be
      delivered and a so-called protein transduction domain. Recently, the derivation
      of cell permeable variants of the DNA recombinase Cre has been reported. Cre is a
      site-specific recombinase that recognizes 34 base pair loxP sites and has been
      widely used to genetically engineer mammalian cells in vitro and in vivo.
      Recombinant cell-permeable Cre recombinase was found to efficiently induce
      recombination of loxP-modified alleles in various mammalian cell lines. Here we
      review recent advances in conditional expression and mutagenesis employing cell
      permeable Cre proteins. Moreover, this review summarizes recent findings of
      studies aimed at deciphering the molecular mechanism of the cellular uptake of
      cell-permeable fusion proteins.

PMID- 17203658
TI  - Analysis of mouse development with conditional mutagenesis.
AB  - Explorations into the molecular embryology of the mouse have played a vital role
      in our understanding of the basic mechanisms of gene regulation that govern
      development and disease. In the last 15 years, these mechanisms have been
      analyzed with vastly greater precision and clarity with the advent of systems
      that allow the conditional control of gene expression. Typically, this control is
      achieved by silencing or activating the gene of interest with site-specific DNA
      recombination or transcriptional transactivation. In this review, I discuss the
      application of these technologies to mouse development, focusing on recent
      innovations and experimental designs that specifically aid the study of the mouse
      embryo.

PMID- 17203659
TI  - Conditional mouse models of cancer.
AB  - The development of inducible and conditional technologies allowed us to generate
      transgenic mouse models that faithfully recapitulate human tumorigenesis. It is
      possible to control, in time and space, the development of tumors in almost every
      mouse tissue. The result is that now we have available mouse models for all major
      human cancers. Novel noninvasive approaches to tumor imaging will enable us to
      follow tumor development and metastasis in vivo, as well as the effects of
      candidate therapeutic drugs. Such new generation tumor models, which accurately
      emulate the disease state in situ, should provide a useful platform with which to
      experimentally test drugs targeted to specific gene products, or combinations of
      genes that control rate-limiting steps of tumor development. In this review, we
      focus on the different mouse models for colon cancer.

PMID- 17203660
TI  - Conditional mutagenesis reveals immunological functions of widely expressed
      genes: activation thresholds, homeostatic mechanisms and disease models.
AB  - Evolutionarily conserved, widely expressed genes provide the functional backbone
      of most, if not all, cell types. Although mouse mutants created by germ line gene
      inactivation are instrumental in establishing the importance of such genes in
      vivo, distortion of embryonic development or multiple body systems often preclude
      detailed functional studies. To overcome this limitation, DNA recombination
      systems such as Cre/loxP of bacteriophage P1, have been adapted for use in
      mammalian cells. The mutagenic event is restricted to the tissue or cell type in
      question leaving other body systems undisturbed. Conditional inactivation of Csk
      or Socs3, for example, established their key role in the prevention of
      inappropriate inflammation, while unexpected immunoregulatory activities emerged
      from studies of the NF-kappaB and AP-1 pathways. Also, cell types responsible for
      protective or pathogenic TNFalpha production have been identified. Inactivation
      of immunoregulatory receptors in leukocyte subsets can provide robust
      experimental systems revealing the conceptual simplicity underlying the
      modulation of complex signaling pathways during homeostatic responses. As
      illustrated for TGF-beta receptor, such system-guided approaches can provide a
      comprehensive picture of the regulatory events driving in vivo phenotype and
      specific responses of primary cells. This in turn facilitates the identification
      of novel regulatory mechanisms, targets for therapeutic intervention and
      prediction of side effects. With the increasing evidence for a role of somatic
      mutations in a wider range of human diseases, conditional mouse models are set to
      play a continuing part in the identification of pathogenic mechanisms for
      restoration of normal cellular processes in diseases including cancer,
      inflammation and autoimmunity.

PMID- 17203661
TI  - Conditional transgenesis and recombination to study the molecular mechanisms of
      brain plasticity and memory.
AB  - In the postgenomic era, a primary focus of mouse genetics is to elucidate the
      role of individual genes in vivo. However, in the nervous system, studying the
      contribution of specific genes to brain functions is difficult because the brain
      is a highly complex organ with multiple neuroanatomical structures, orchestrating
      virtually every function in the body. Further, higher-order brain functions such
      as learning and memory simultaneously recruit several signaling cascades in
      different subcellular compartments and have highly fine-tuned spatial and
      temporal components. Conditional transgenic and gene targeting methodologies,
      however, now offer valuable tools with improved spatial and temporal resolution
      for appropriate studies of these functions. This chapter provides an overview of
      these tools and describes how they have helped gain better understanding of the
      role of candidate genes such as the NMDA receptor, the protein kinase
      CaMKIIIalpha, the protein phosphatases calcineurin and PP1, or the transcription
      factor CREB, in the processes of learning and memory. This review illustrates the
      broad and innovative applicability of these methodologies to the study of brain
      plasticity and cognitive functions.

PMID- 17203662
TI  - A novel conditional knockout strategy applied to serotonin receptors.
AB  - Here we demonstrate the feasibility of a doubly regulatable transgenic mouse
      design that allows for gene manipulation by both Cre-recombinase and the
      tetracycline inducible system. Using a knock-in strategy to insert both elements
      of the tetracycline inducible system and a neomycin (neo) cassette flanked by
      loxP sequences (floxed) into the wild-type locus, we generated mice that express
      the 5-HT(1B) receptor in a conditional manner. In the presence of a floxed neo
      cassette, receptor expression was silenced. Removal of this cassette by Cre
      mediated recombination led to 5-HT(1B) receptor expression, which was highly
      regulatable when doxycycline, a derivative of tetracycline, was administered to
      the mice. This system allowed for a determination of an in vivo time course of
      receptor half-life and recovery. Physiological studies also demonstrated that
      rescued 5-HT(1B) receptors were functional, and that this functionality was
      reversible upon treatment with doxycycline. Crossing mice where the 5-HT(1B), or
      the 5-HT(1A), receptors were silenced by the neo-cassette, with mice expressing
      either Cre-recombinase or the tetracycline transactivator (tTA) under the control
      of tissue-specific promoters, led to tissue-specific re-expression of these
      receptors. Our studies thus demonstrate the potential of this strategy for
      achieving both a classic knockout, as well as subsequent tissue-specific and/or
      inducible knockouts.

PMID- 17203663
TI  - Conditional mouse models for Friedreich ataxia, a neurodegenerative disorder
      associating cardiomyopathy.
AB  - Friedreich ataxia (FRDA), the most common recessive ataxia, is characterized by
      degeneration of the large sensory neurons and spinocerebellar tracts and
      cardiomyopathy. It is caused by severely reduced levels of frataxin, a
      mitochondrial protein involved in iron-sulfur cluster (ISC) biosynthesis. Mouse
      models have been important tools in dissecting the steps of pathogenesis in FRDA.
      Furthermore, animal models that reproduce some of the key events in a pathology
      are essential for the development of effective therapies, both pharmacological
      and gene therapy approaches. This chapter presents an overview of the current
      mouse models that have been developed for FRDA.

PMID- 17203664
TI  - Animal models in cardiovascular diseases: new insights from conditional models.
AB  - Conditional systems have proven to be efficient and powerful to delineate several
      aspects of cardiac pathophysiology and diseases. The possibility of addressing a
      particular time point in animal life is certainly an important breakthrough
      allowed by conditional strategies with temporal control of either transgene
      expression or gene modifications. The purpose of this review is to present
      various mouse models for cardiovascular diseases based on conditional approaches.

PMID- 17203665
TI  - Conditional animal models for the study of lipid metabolism and lipid disorders.
AB  - The advent of technologies that allow conditional mutagenesis has revolutionized
      our ability to explore gene functions and to establish animal models of human
      diseases. Both aspects have proven to be of particular importance in the study of
      lipid-related disorders. Classical approaches to gene inactivation by
      conventional gene targeting strategies have been successfully applied to generate
      animal models like the LDL receptor- and the apolipoprotein E-knockout mice,
      which are still widely used to study diverse aspects of atherosclerosis, lipid
      transport, and neurodegenerative disease. In many cases, however, simply
      inactivating the gene of interest has resulted in early lethal or complex
      phenotypes which are difficult to interpret. In recent years, additional tools
      have therefore been developed that allow the spatiotemporally controlled
      manipulation of the genome, as described in detail in Part I of this volume. Our
      aim is to provide an exemplary survey of the application of different conditional
      mutagenesis techniques in lipid research in order to illustrate their potential
      to unravel physiological functions of a broad range of genes involved in lipid
      homeostasis.

PMID- 17203666
TI  - Conditional mouse models to study developmental and pathophysiological gene
      function in muscle.
AB  - This chapter will review conditional mouse model systems that have been developed
      to study gene function in skeletal, cardiac, and vascular smooth muscle cells in
      vivo with an emphasis on the utility of these models for investigating
      developmental and pathophysiological gene function in muscle. In general, these
      systems have utilized muscle-specific/selective promoter-enhancers in conjunction
      with site-specific DNA recombinases, e.g., Cre-loxP, and fusion proteins with
      these recombinases that confer temporal control, such as tamoxifen-inducible
      CreER systems. A major focus of this chapter will be to discuss unique challenges
      of studying Cre-mediated mutagenesis/gene targeting in these muscle types during
      development and in the adult animal, some of which are inherent of the muscle
      cell type being studied. For example, unlike cardiac and skeletal muscle cells,
      the vascular SMC is extremely plastic and able to undergo rapid phenotypic
      modulation to various environmental cues in vivo. Thus, employing SMC marker gene
      promoter enhancers for conditional gene targeting in SMCs must take into account
      the possibility and/or certainty that the particular SMC promoter enhancers used
      may or may not be transcriptionally active in SMCs of a vessel wall under normal
      and some pathophysiological conditions. Moreover, individual floxed loci within
      the same muscle cell type and tissue have different degrees of sensitivity to
      Cre, most likely dependent on the chromatin state of that particular gene, i.e.,
      closed/condensed state or open/active state. Thus, Cre recombination may be
      ineffective for specific floxed gene DNA. Lastly, rigorous efforts must be made
      to confirm the degree of recombination in a tissue, taking into full account the
      multicellularity of the tissue, to understand the extent of the physiological
      effect in that organ.

PMID- 17203667
TI  - Analysis of calcium channels by conditional mutagenesis.
AB  - Ca2+ influx through various ion channels is an important determinant of the
      cytosolic Ca2+ concentration, which plays a pivotal role in countless cellular
      processes. The cardiac L-type Ca2+ channel, Ca(v)1.2, represents a major pathway
      for Ca2+ entry and is in many cells expressed together with other high- and low
      voltage-activated Ca2+ channels. This article will focus on the use of
      conditional transgenic mouse models to clarify the roles of Ca2+ channels in
      several biological systems. The phenotypes of conditional Ca2+ channel transgenic
      mice have provided novel, and often unexpected, insights into the in vivo
      function of L-type and T-type Ca2+ channels as mediators of signaling between
      cell membrane and intracellular processes in blood pressure regulation, smooth
      muscle contractility, insulin secretion, cardiac function, sleep, learning, and
      memory.

PMID- 17203668
TI  - Conditional mutagenesis of G-protein coupled receptors and G-proteins.
AB  - The G-protein-coupled receptor signaling system, consisting of a huge variety of
      receptors as well as of many G-proteins and effectors, operates in every cell and
      is involved in many physiological and pathological processes. The versatility of
      this system and the involvement of specific components makes G-protein-coupled
      receptors and their signaling pathways ideal targets for pharmacological
      interventions. Classical mouse knockout models have often provided important
      preliminary insights into the biological roles of individual receptors and
      signaling pathways and they are routinely used in the process of target
      validation. The recent development of efficient conditional mutagenesis
      techniques now allows a much more detailed analysis of G-protein-mediated
      signaling transduction processes. This review summarizes some of the areas in
      which progress has recently been made by applying conditional mutagenesis of
      genes coding for G-proteins and G-protein-coupled receptors.

PMID- 17203669
TI  - Contribution of targeted conditional somatic mutagenesis to deciphering retinoid
      X receptor functions and to generating mouse models of human diseases.
AB  - The last decade has witnessed an enormous rise in the interest for retinoid
      signalling and its cognate receptors, because of their central role in the
      coordination of development and homeostasis, through their ability to orchestrate
      the expression of numerous target genes. These receptors include six nuclear
      receptor (NR) family members, the retinoic acid receptor (RAR) alpha, beta and
      gamma, and the retinoid X receptor (RXR) alpha, beta and gamma, which are
      expressed in many cell types in mammals. Analysis of the development of mouse
      embryos bearing retinoid receptor null mutations demonstrated that these
      receptors transduce the effects of retinoic acid (RA, the active derivative of
      vitamin A) in vivo, and revealed impressive complexity. However, frequent
      redundancy in receptor functions and lethality of compound RAR-null mutants, as
      well as of RXRalpha-null mutants, precluded the characterisation of the functions
      of these receptors during late development and postnatally. We illustrate here
      how recent developments of conditional targeted somatic mutagenesis have opened
      new avenues in analysing the physiological functions of retinoid X receptor
      signalling in a variety of tissues and cell types, as well as in exploring the
      pathophysiological consequences of their alteration that led to novel mouse
      models of human diseases.

PMID- 17203670
TI  - Evaluation of occupational therapy interventions for elderly patients in Swedish
      acute care: a pilot study.
AB  - The aim was to evaluate whether occupational therapy interventions in acute care
      could improve the elderly patient's perception of ability to manage at home after
      discharge. A pilot study was performed, including 22 patients in the experimental
      group and 19 in the control group. Occupational therapy interventions were
      conducted in the experimental group concerning personal care, information,
      prescription of assistive devices, planning of discharge, and reporting to
      primary care or community care. The control group was given no occupational
      therapy interventions. Structured interviews were performed on discharge and at a
      follow-up in about 14 weeks after discharge. The two groups were comparable
      concerning gender, age, days of care, and diagnoses. Patients in the experimental
      group scored lower on mental health and were more anxious on discharge. However,
      there was no difference between the groups in managing at home after discharge.
      Patients in the control group had greater need of further contacts with
      healthcare after discharge. Due to the small sample interpretations must be made
      with caution. The findings indicate that occupational therapy interventions in
      acute care might have a positive effect from the perspective of the elderly
      patient. These results need to be confirmed in a larger study.

PMID- 17203671
TI  - Occupation and meaning in the lives of women with chronic pain.
AB  - The aim of this study was to examine how women experience occupations as they
      live with chronic pain and more specifically to gain detailed knowledge regarding
      the meaning of important occupations in their life. The article is based on an
      analysis of 17 narratives based on an Occupational Performance History Interview.
      Participants were interviewed as part of their occupational therapy assessment at
      Orton Rehabilitation. The narratives were analysed in order to identify the
      experiences of doing occupations in everyday life. When interpreting their
      problems in and solution for doing occupations women in this study used four
      basic metaphors: (1) moving forward, (2) slowing down, (3) fighting and (4)
      standing still. The tone of the narratives varied from hopeful to hopeless and
      from fearful to frustrated. Each of these four types of narratives differed in:
      (a) the tone of the narrative, (b) the meaning ascribed to occupation, (c) how
      others are viewed in relation to one's doing, and (d) how the future is
      envisioned. The experience of occupation in the lives of women with chronic pain
      is heterogeneous and depends on the underlying meaning of the narrative used to
      experience and interpret occupational life.

PMID- 17203672
TI  - Living with a person with Alzheimer's disease: experiences related to everyday
      occupations.
AB  - The aim of this study was to illuminate experiences of daily occupations among
      spouses living with a person with Alzheimer's disease (AD). The study contains
      phenomenological-hermeneutic interpretation of interviews with eight spouses. The
      analysis revealed the participants as being in the process of a changing
      occupational situation. They come to live an occupational life intertwined with
      their partners' needs. An ongoing process of occupational adjustment is taking
      place as a response to the changing situation. The spouses were occupied with
      consequences of their partner's disease. They were striving for occupational
      meaning and at the same time living with threats to meaningful occupations. It
      can be concluded that living with a partner with AD is a complex dealing with
      occupational meaning. This complexity should be considered in interventions.

PMID- 17203673
TI  - The Tree Theme Method in psychosocial occupational therapy: a case study.
AB  - This study aimed to describe the Tree Theme Method (TTM) as a method for
      intervention in psychosocial occupational therapy. The TTM is based on theories
      concerning creative activities and occupational storytelling and story making. In
      order to exemplify the method a case study of a treatment process with follow up
      was undertaken. The participant was a female client suffering from anxiety and
      depression. During an interview the client painted symbolic trees on five
      different occasions with specific variations of the tree theme: a tree
      symbolizing her present life, her childhood, adolescence, adulthood, and,
      finally, a tree representing her future. The trees were used as starting points
      for the client to tell her life story. The intention was that she would find new
      strategies for how to change her daily life. Three years later there was a follow
      up stage where the client painted new trees and told her story. Some life themes
      were identified. The TTM appears suitable for intervention in psychosocial
      occupational therapy. In future studies the TTM should be subjected to evaluation
      research based on several clients in order to develop a deeper understanding of
      the process and what kind of results changes in the TTM intervention may provide.

PMID- 17203674
TI  - The complexity of daily occupations in multiple sclerosis.
AB  - The aims of this study were to describe which self-care, productivity, and
      leisure occupations individuals with multiple sclerosis (MS) perceive as
      difficult to perform on admission to rehabilitation and the individuals' own
      perception of the importance of, performance of, and satisfaction with these
      occupations. Whether the reported self-care, productivity, and leisure
      occupations were related to sex, age, disease severity, and living arrangements
      was also investigated. Forty-seven men and women (mean age 49.4 years) were
      assessed with the Canadian Occupational Performance Measure (COPM) on admission
      to rehabilitation. The individuals reported 366 occupations (median 8, range 3
      15), which were categorized as self-care (51%), productivity (30%), and leisure
      (19%). Three COPM subcategories--household management (26%), personal care (21%),
      and functional mobility (20%)--accounted for two-thirds of the reported
      occupations. All prioritized occupations (n = 238; (median 5, range 2-7) had high
      ratings for importance and the ratings for performance and satisfaction were
      generally low. Men reported significantly more occupations related to self-care
      than women, but no significant difference between the sexes could be found for
      productivity and leisure. No significant differences between the occupational
      areas were found when age, disease severity, or/and living arrangements were
      included in the analysis. In conclusion, individuals with MS perceive
      difficulties with occupations related to all aspects of daily life. This
      underscores the need to use assessment tools that capture the complexity of daily
      occupations.

PMID- 17203675
TI  - The role of perceived control for the perception of health by patients with
      persistent mental illness.
AB  - Perceived control has been found to be of significance for patients with
      psychiatric disorders and may be regarded as an aspect of empowerment. Moreover,
      a sense of control has been identified as important for occupational performance,
      both in empirical research and in occupational therapy theory. This study aimed
      at investigating factors that might be of importance for perceived control:
      sociodemographic, clinical, and well-being variables. Another aim was to
      investigate whether perceived control served as a mediator between clinical
      variables, in terms of psychopathology, and well-being variables, in terms of
      perceived health. Sociodemographic data were collected from 177 subjects, most of
      them with psychosis diagnoses. They were also assessed regarding perceived
      control (locus of control and self-mastery) and different aspects of health and
      well-being. The findings showed that both clinical and well-being variables were
      consistently related to both aspects of perceived control. Moreover, the roles of
      self-mastery and locus of control as mediators of perceived health were
      identified. The results also identified some important sociodemographic factors
      that might promote a sense of control and empowerment, mainly educational level
      and friends. This study provided detailed knowledge of the role of perceived
      control for well-being among people with mental disorders. Strategies for how
      occupational therapists may promote a sense of control in this group are
      discussed.

PMID- 17203676
TI  - Stem cell research in India: from hype and hope to reality.

PMID- 17203677
TI  - Aetiological, clinical and metabolic profile of hypokalaemic periodic paralysis
      in adults: a single-centre experience.
AB  - BACKGROUND: Hypokalaemic periodic paralysis constitutes a heterogeneous group of
      disorders that present with acute muscular weakness. In this analysis, we discuss
      the aetiological factors that appear to be more common in the Indian population.
      METHODS: From 1995 to 2001, 31 patients presented with periodic paralysis (mean
      age 34.5 years, range 11-68 years). Of the 31 patients, 19 were men. The clinical
      and laboratory data of these patients were analysed. Patients were investigated
      for possible secondary causes of hypokalaemla. RESULTS: There were 13 patients
      (42%) with renal tubular acidosis, 13 with primary hyperaldosteronism (42%), 2
      each with thyrotoxic periodic paralysis and sporadic periodic paralysis, and I
      with Gitelman syndrome. Of the 13 patients with renal tubular acidosis, 10 had
      proximal and 3 distal renal tubular acidosis. Three of these patients with renal
      tubular acidosis had Sjogren syndrome. The patients diagnosed to have renal
      tubular acidosis had significantly lower serum bicarbonate (18.7 [14.6] v. 29.6
      [5.0] mEq/L; p < 0.05) and higher levels of chloride (107.5 [6.0] v. 99.5 [3.4]
      mEq/L; p < 0.05) compared with those who had primary hyperaldosteronism, although
      the potassium values were similar (2.4 [0.65] v. 2.26 [0.48] mEq/L; p = 0.43).
      All patients with primary hyperaldosteronism had hypertension at presentation and
      were proven to have adrenal adenomas. CONCLUSION: A significant number of
      patients in this study had secondary and potentially reversible causes of
      hypokalaemic periodic paralysis. The common causes were renal tubular acidosis
      and primary hyperaldosteronism. A detailed work-up for secondary causes should be
      undertaken in Indian patients with hypokalaemic periodic paralysis.

PMID- 17203678
TI  - Spectrum of severe chronic kidney disease in India: a clinicopathological study.
AB  - BACKGROUND: The healthcare burden due to chronic kidney disease has increased
      worldwide in the past decade. Elucidating the aetiology of chronic kidney disease
      may help in identifying strategies for prevention, both in the population and the
      Individual patient. Only a clinicopathological study can define the exact
      spectrum of chronic kidney disease since epidemiological studies have not shown a
      consistent aetiological profile. The histological evidence used to support the
      diagnosis varies with the degree to which renal biopsy is done. Renal biopsy is
      the gold standard in making an aetiological diagnosis in renal failure, but as a
      diagnostic tool in chronic kidney disease it is underutilized. METHODS: This
      prospective study done at Christian Medical College, Vellore in southern India
      from 1998 to 2003 aimed to determine the aetiological profile of severe chronic
      kidney disease by analysing renal biopsies. The value of pre-renal biopsy
      clinical Judgement in predicting the histological diagnosis was also assessed.
      Patients with diabetic nephropathy were excluded from the study. RESULTS: Four
      hundred and fifty-seven patients had evidence of chronic kidney disease as
      evidenced on biopsy as well as on clinical parameters. Three hundred and twenty
      two of these patients (70.5%) had glomerulonephritis as the histological
      diagnosis. Fifty-five (12%) had Interstitial nephritis, 30 (6.6%) had
      hypertensive arteriosclerosis and 28 (6.1%) had metabolic nephropathies. The
      positive predictive value of a pre-biopsy clinical diagnosis in predicting
      interstitial nephritis was very low (33%). A large number of patients clinically
      diagnosed to have chronic interstitial nephritis had other aetiologies of chronic
      kidney disease. CONCLUSION: Glomerulonephritis was the most common cause of
      chronic kidney disease, not including diabetic nephropathy, followed by
      interstitial disease and benign arterionephrosclerosis. In patients with
      unidentified severe chronic kidney disease, renal biopsy provided an aetiological
      diagnosis.

PMID- 17203679
TI  - Nephrotic syndrome and recurrent pulmonary oedema in bilateral atherosclerotic
      renal artery stenosis: resolution following renal angioplasty and stenting.
AB  - Hypertension and episodic pulmonary oedema are known complications of bilateral
      renovascular disease. However, significant proteinuria has not been reported in
      this setting. We describe a patient who presented with recurrent pulmonary oedema
      and nephrotic syndrome, and was found to have bilateral renal artery stenosis.
      Percutaneous angioplasty and stenting led to a complete resolution of both,
      confirming a causal relationship. This is perhaps the first report documenting
      the rare combination of nephrotic syndrome and flash pulmonary oedema due to
      bilateral renal artery stenosis.

PMID- 17203680
TI  - Chronic myelogenous leukaemia (CML): an update.
AB  - The management of chronic myelogenous leukaemia (CML) has undergone a major
      change over the past 5 years. All newly diagnosed patients of CML are candidates
      for imatinib mesylate therapy. Almost 95% of patients with early chronic phase
      CML achieve complete haematological remission (CHR) and nearly 80% achieve
      complete cytogenetic response (CGR; 0% Philadelphia [Ph] chromosome-positive
      metaphases). These responses are stable in most patients with a risk of relapse
      of 4%-6% per year. For patients with advanced CML (accelerated phase and blast
      crisis), achievement of CHR and major (complete and partial) CGR occurs in 25%
      37% and 10%-30% of patients, respectively. Most investigators agree that patients
      who fail to achieve CHR by 12 weeks, have partial cytogenetic response (< 35% Ph
      positive metaphases) at 12 months, have CGR by 18 months, who relapse after
      initial response to imatinib, and those with a high Sokal score or in an advanced
      phase of CML should be considered for allogeneic stem cell transplantation (SCT).
      Despite Ph negativity with imatinib treatment, most patients continue to remain
      BCR-ABL positive on molecular studies, and require treatment indefinitely.
      Identification of patients at high risk for relapse and understanding the
      mechanisms to unravel resistance to imatinib are current areas of active
      research.

PMID- 17203681
TI  - Is short duration trastuzumab adequate adjuvant therapy for HER-2 overexpressing
      breast cancers?

PMID- 17203682
TI  - Pulmonary artery catheter: no more indiscriminate use!

PMID- 17203683
TI  - The chest radiograph.

PMID- 17203684
TI  - Helping members of a community-based health insurance scheme access quality
      inpatient care through development of a preferred provider system in rural
      Gujarat.
AB  - We describe and analyse the experience of piloting a preferred provider system
      (PPS) for rural members of Vimo SEWA, a fixed-indemnity, community-based health
      insurance (CBHI) scheme run by the Self-Employed Women's Association (SEWA). The
      objectives of the PPS were (i) to facilitate access to hospitalization by
      providing financial benefits at the time of service utilization; (ii) to shift
      the burden of compiling a claim away from members and towards Vimo SEWA staff;
      and (iii) to direct members to inpatient facilities of acceptable quality. The
      PPS was launched between August and October 2004, in 8 subdistricts covering
      15,000 insured. The impact of the scheme was analysed using data from a household
      survey of claimants and qualitative data from in-depth interviews and focus group
      discussions. The PPS appears to have been successful in terms of two of the three
      primary objectives--it has transferred much of the burden of compiling a health
      Insurance claim onto Vimo SEWA staff, and it has directed members to inpatient
      facilities with acceptable levels of technical quality (defined in terms of
      structural Indicators). However, even under the PPS, user fees pose a financial
      barrier, as the insured have to mobilize funds to cover the costs of medicines,
      supplies, registration fee, etc. before receipt of cash payment from Vimo SEWA.
      Other barriers to the success of the PPS were the geographic Inaccessibility of
      some of the selected hospitals, lack of awareness about the PPS among members and
      a variety of administrative problems. This pilot project provides useful lessons
      relating to strategic purchasing by CBHI schemes and, more broadly, managed care
      in India. In particular, the pragmatic approach taken to assessing hospitals and
      identifying preferred providers is likely to be useful elsewhere.

PMID- 17203685
TI  - Does the TGN1412 trial disaster have lessons for clinical trials in India?

PMID- 17203686
TI  - Australia's reputation in the eyes of the international community.

PMID- 17203687
TI  - Advertising again.

PMID- 17203688
TI  - The world: a different view.

PMID- 17203689
TI  - Guidelines, planning and training will help in a coordinated disaster response.

PMID- 17203690
TI  - 'Impact factor' and 'immediacy index' of The National Medical Journal of India.

PMID- 17203691
TI  - Local and illicit alcohol in India.

PMID- 17203692
TI  - [Chance finding of foetal and neonatal ovarian cysts on echography].
AB  - Cystic abnormalities of the adnex were found by chance in 2 baby girls, one aged
      2.5 months and the other aged 2 months. Both had been born dysmaturely and the
      abnormalities were found on echographic investigation carried out for suspected
      urinary-tract infection. On monitoring investigation one month later, the
      abnormalities had become smaller and some time later had disappeared altogether.
      With the increasing use of ultrasound, ovarian cysts are being detected more
      often in the foetus and neonate. The majority of these cysts are benign
      functional follicular cysts and resolve spontaneously. The decision to perform
      surgery depends on the clinical symptoms and appearance on ultrasound. Large
      uncomplicated cysts can be managed by antenatal or postnatal aspiration in order
      to prevent torsion and the subsequent loss of the adnex.

PMID- 17203693
TI  - [Stenting of symptomatic stenosis of the internal carotid artery is not preferred
      over endarterectomy at this time].
AB  - Carotid endarterectomy reduces the risk of stroke in patients with symptomatic
      internal carotid-artery stenosis of 50% or greater. Carotid-artery stenting may
      be an attractive alternative. Two randomised trials comparing carotid
      endarterectomy with stenting have recently been terminated prematurely. Reasons
      for termination included an excess in stroke and death after stenting, compared
      with carotid endarterectomy (the EVA-3S trial) and futility reasons and the
      absence of funding (the SPACE trial). Given that both trials failed to prove the
      non-inferiority of stenting compared with carotid endarterectomy in the first 30
      days, the use of stenting should be restricted to patients with contraindications
      to surgery and those participating in randomised clinical trials.

PMID- 17203694
TI  - [Reduce the mortality due to femur fractures via an integrated approach to the
      comorbidity].
AB  - Preliminary studies show that there is an annual increase in the number of
      operations for femur fractures in The Netherlands and that this increase can be
      ascribed totally to the increasing age of the population, even though the risk of
      falling has not increased. Although the hospital mortality in this category of
      patients has decreased, mainly as the result of a shortened hospital stay, the
      long-term mortality does not seem to have decreased in comparison to earlier
      analyses. The conclusion could well be that we in The Netherlands must be able,
      in the future, to reduce the long-term mortality by means of a better integrated
      approach to care, as has already been described in other studies.

PMID- 17203695
TI  - [Provisions for potentially raising the age limit for oocyte donation].
AB  - The introduction ofoocyte donation has provided a new perspective on reproduction
      for women with premature ovarian failure. In contrast to other forms ofassisted
      reproductive technology, the success ofoocyte donation is not affected by the age
      of the future mother. This has prompted a discussion on raising the age limit to
      allow older women to become pregnant. The health risk for the future mother is
      increased in older women compared with younger women but does not appear to be a
      sufficient reason to disqualify older women from undergoing the procedure. Lack
      of information regarding the effect of very late parenthood on the medical,
      psychological and social well-being of the future child poses the greatest
      concern. Should the age limit be extended for oocyte donation, treatment should
      be restricted to a research setting with a protocol for single-embryo transfer
      and extensive follow-up regarding the well-being of the future child.

PMID- 17203696
TI  - [Pregnancy at a later age with the help of oocyte donation].
AB  - An increasing number of women are delaying childbirth until an age when their
      fertility has significantly declined. Oocyte donation provides the opportunity
      for women to successfully conceive regardless of age. In The Netherlands, in 1997
      the age limit for oocyte donation treatment was set at 45 years. The most
      important objections to pregnancy in older women are the medical risks for mother
      and child, the application of fertility treatments beyond the natural
      reproductive age and the psychosocial consequences for the child. However, based
      on international experience and recent data concerning the risks of pregnancy
      after oocyte donation in older women, it is proposed to increase the maximum age
      limit for this procedure to 50 years.

PMID- 17203697
TI  - [The hygiene hypothesis: a fruitful concept in immunological research].
AB  - There is no longer any discussion about the first part of the hygiene hypothesis:
      insufficient stimulation of the developing immune system in young children leads
      to a disordered immune system that does not know when to react and when not to
      react to external or internal stimuli. The second part of the hypothesis states
      that this disordered immune response is responsible for the worldwide increase in
      allergies during the past 30 years. Randomised studies on this subject are
      impossible. It is clear, however, that micro-organisms can contribute to the
      development of a vigorous immune system and thus decrease the risk of allergy.
      The hygiene hypothesis is very much alive in immunological research.

PMID- 17203698
TI  - [The hygiene hypothesis is invalid].
AB  - The hygiene hypothesis offers an interesting explanation for the recent increase
      in allergy. However, all the studies that support this hypothesis are
      observational and cohort studies, which implies that no causal relationships can
      be assessed with sufficient validity. Exposure to environmental allergens and
      infections may very well not be determined by chance but by the behaviour of the
      parents. Therefore, the hygiene hypothesis should not be accepted without
      critical reflection of the facts presented.

PMID- 17203699
TI  - [Diagnostic image (301). A man with a protruding tibial fragment].
AB  - A 55-year-old man presented with a chronic osteomyelitis of the tibia. A
      sequestrum had already been formed; it protruded through the skin. The sequestrum
      was easily removed and the wound healed per secundam.

PMID- 17203700
TI  - [Proximal femur fractures in the elderly in The Netherlands during the period
      1991-2004: incidence, mortality, length of hospital stay and an estimate of the
      care capacity needed in the future].
AB  - OBJECTIVE: To assess the incidence of operations for neck and pertrochanteric
      femur fractures during the last 15 years and to estimate the future demand for
      such operations in The Netherlands. DESIGN: Retrospective. METHOD: For the years
      1991, 1995, 2000 and 2004, the following anonymised data were collected in the
      National Medical Registry of Prismant for all patients admitted to Dutch
      hospitals for a hip fracture: age-group, gender, length of pre- and postoperative
      hospital stay, destination after discharge and hospital mortality. These data
      were related to demographic data for the Dutch population from Statistics
      Netherlands (CBCS) and to estimates for the Dutch population in the future from
      Primos Prognostic Data. RESULTS: The average absolute increase in the period 1991
      2004 was linear, with 230 fractures per year. Women were operated for a hip
      fracture 1.5-2 times as often as men in the same age range. The age-specific
      incidence remained constant over the years but the absolute number of elderly
      persons per age group increased. The average length of pre- and postoperative
      hospital stay was reduced by half during the period under investigation. The
      postoperative hospital mortality decreased from 8.1% in 1991 to 5.6% in 2004, and
      was 1.5 times as high for men aged 70 years or over as for women of the same age
      group. In 2004 as compared to 1991, 2.5 times as many patients were discharged to
      a nursing home. In view of the increasing age of the population, the total number
      of operated hip fractures can be expected to be 20,200 in the year 2010 and
      23,900 in the year 2020. CONCLUSION: In the period 1991-2004 there was an annual
      increase of 230 operations for proximal femur fractures that was closely related
      to the ageing of the Dutch population. During the years under investigation, the
      incidence in the same age range was higher in women, but men had a higher
      hospital mortality. It is estimated that the decreasing hospital mortality and
      the decrease in the length of hospital stay will increase the need for nursing
      home care for this category of patients.

PMID- 17203701
TI  - [An asymmetrical face due to torticollis in two young children].
AB  - In 2 girls, 4 years and 8 months of age, respectively, torticollis had been
      diagnosed a few weeks after birth. Kinesiotherapy, given for a period of 1 year
      and 6 months, respectively, had little effect. Both girls were then referred to
      the Orthopaedic Outpatient Clinic where a shortened sternocleidomastoid muscle
      and an asymmetrical face were diagnosed. The shortened muscle was cleaved
      surgically. Over half a year later, the face of the older child was still
      asymmetrical but that of the younger child symmetric. It is recommended that
      children with torticollis due to a shortened sternocleidomastoid muscle first be
      given stretch exercises under the guidance of a physiotherapist. If the result at
      the age of 1 year is unsatisfactory, an orthopaedic surgeon can then cleave the
      muscle.

PMID- 17203702
TI  - [Formation of a pseudocyst following abdominoplasty].
AB  - A 49-year-old woman presented for follow-up examination after an abdominoplasty
      performed in Germany. She complained of pain in the abdomen and was not satisfied
      with the final result. The patient presented with a bulging, painful abdomen. The
      symptoms disappeared for a few weeks after puncture of the seroma, but then
      returned. Neither haematoma, seroma nor neuroma were found at the first
      exploration, but a second abdominoplasty revealed a large pseudocyst extending
      from the epigastric to the supra-pubic area. The pseudocyst was extirpated.
      Seroma formation is a frequently occurring complication after abdominoplasty, but
      is ultimately reabsorbed spontaneously. Pseudocyst formation following
      abdominoplasty is a rare complication, which has been described in the literature
      only when liposuction was done as well. Liposuction creates multiple channels
      that result in an open abdominoplasty cavity. Seroma and blood clots provoke an
      inflammatory response, resulting in a pseudocyst after the formation of a thick
      capsule. The prevention of seroma and haematoma formation is of essential
      importance in preventing this rare complication. Sharp dissection, prolonged
      drainage with high vacuum and a compressive bandage are very important in this
      connection.

PMID- 17203703
TI  - [Airway abnormalities in children].

PMID- 17203704
TI  - [Ethnic differences in suicidal behavior].

PMID- 17203705
TI  - [Secondary prevention of recurrent stroke by lowering cholesterol levels and
      blood pressure].

PMID- 17203706
TI  - [From the Cochrane Library: topical antibiotic treatment is more effective than
      systemic antibiotic treatment for chronic otitis media with eardrum perforation
      and purulent discharge].

PMID- 17203707
TI  - Prevalence of the metabolic syndrome among a determined Puerto Rican population.
AB  - The metabolic syndrome defined as diabetes, hypertension, obesity, dyslipidemia,
      Glucose intolerance and hyperinsulinemia, also known as the syndrome of insulin
      resistance, has been found highly prevalent among Hispanic populations. The
      reason is attributed to the high prevalence of obesity and diabetes due to
      genetic factors, sedentary lifestyle and poor nutritional habits. The association
      of the metabolic syndrome with cardiovascular disease is widely recognized but
      the prevalence of the syndrome varies between studies due to the variations among
      both definitions (ATP III and WHO). We aim to determine the prevalence of the
      metabolic syndrome in a determined Puerto Rican population at the outpatient
      employee's clinic to further support the burden of the metabolic syndrome among
      hispanics. In this study, the ATP III criteria presented higher prevalence of the
      metabolic syndrome than the WHO definition and the modified criteria detected
      more cases of impaired fasting glucose than ATP III. The 32% overall prevalence
      support the NHANES III reported prevalence among Mexican-Americans.

PMID- 17203708
TI  - Alfa 1 antitrypsin and protease levels in Puerto Rican asthmatics: a pilot study.
AB  - A cross-sectional pilot study was conducted on a population of 119 asthmatics who
      had been recruited from the Emergency Room Department of a major hospital in
      Ponce, Puerto Rico. The purpose of the study was to determine the frequency of
      the MM, MS, and SS a-i-antiprotease variants. Also, we analyzed the serum levels
      of the alpha-1-antiprotease inhibitor, quantified the levels of serine proteases
      in homes of the asthmatic volunteers, and determined whether environmental levels
      of proteases, regardless of their sources, had any association with either asthma
      symptoms or alpha-1-antiprotease inhibitor phenotypes. Our results do not support
      the role of the alpha-1-antiprotease as a risk factor for asthma in the study
      population as previously reported. Patients who had visited the ED due to asthma
      on 3 or more occasions had significantly higher trypsin levels than those who had
      done so 2 or fewer times. Of those asthmatic patients who had daily symptoms, 40%
      had been exposed to high levels of elastase, and 33.3% to trypsin. Similarly,
      52.9% of the patients with 2 or more hospitalizations a year had been exposed to
      high elastase levels, and 40.5% of asthma patients who had nocturnal asthma more
      than 3 times a week had been exposed to high levels of elastase.

PMID- 17203709
TI  - Factor structure of the Beck Depression Inventory-Second Edition (BDI-II) with
      Puerto Rican elderly.
AB  - The Beck Depression Inventory-Second Edition (BDI-II; (1) is one of the most
      useful measures for depressive symptomatology in many countries (2). The
      psychometric properties of this inventory, however, have not been reported with
      Puerto Rican elderly. This paper reports, exploratory psychometric results with a
      sample of 410 elderly Puerto Rican (65 years and older; men=94, women=316). The
      assessment of the construct validity of the BDI-II yielded four factors
      accounting for 52% of total variance and an internal reliability coefficient
      (alpha Cronbach) of .89. A factor analysis with the 21 items of the BDI-II was
      performed using principal component analysis as the extraction method and Varimax
      rotation. This analysis revealed that the BDI-II was a good measure of the
      dimensions of depressive symptomatology in the present sample, which resembled
      prior findings reported with the general Puerto Rican Population (3). This study
      also reports further data supporting the reliability, validity, and practical
      utility of the BDI-II for the Puerto Rican population including elders.
      Implications for potential research with minorities and clinical uses of the BDI
      II are also discussed.

PMID- 17203710
TI  - The prevalence of pit and fissure sealants among twelve year olds living in
      Puerto Rico during 1997.
AB  - OBJECTIVE: to estimate the prevalence of pit and fissure sealants on first
      permanent molars in twelve year olds living in Puerto Rico and to further
      evaluate dental sealant prevalence by (1) urban/rural and public/private school
      status as well as (2) gender; DESIGN: population-based, cross-sectional study.
      SETTING: public and private schools encompassing the 11 health regions of Puerto
      Rico. SUBJECTS: a probabilistic sample of 12-year old school attendees in Puerto
      Rico representing a population of approximately 70,000. METHOD: during April
      through December 1997, the first permanent molars of 1435 subjects were evaluated
      by visual and tactile methods for the presence of dental sealants. RESULTS: the
      data collected revealed that 4.3% of 12 years olds presented at least one
      permanent first molar sealed. A statistically significant difference (p = 0.01)
      between urban-public (2.5%), rural-public (3.39%) and urban-private (11.0%)
      schools was observed. The prevalence of sealants was higher in males (5.5%) than
      females (2.9%); (p = 0.02). CONCLUSIONS: the prevalence of dental sealants in the
      first permanent molars of 12-year olds living in Puerto Rico during 1997 (4.3%)
      is lower than that reported in the United States (18.5%). Sealant prevalence was
      higher in males and students attending (urban) private schools.

PMID- 17203711
TI  - Plasma ascorbate in a population of children: influence of age, gender, vitamin C
      intake, BMI and smoke exposure.
AB  - The objective of this study is to determine the influence of several personal and
      lifestyle factors on the levels of circulating vitamin C in a population of
      children. To accomplish this objective, blood samples were collected from 511
      healthy children residing in the Greater San Juan area. The population was
      stratified into 4 percentile groups (approaching quartiles) according to plasma
      ascorbate levels from lowest to highest concentrations. Comparisons were made
      between percentile groups on the basis of age, gender, body mass index (BMI),
      dietary intake of vitamin C (corrected and uncorrected for energy intake) and
      exposure to environmental tobacco smoke (ETS). Smoke exposure was determined
      using urinary cotinine, which is a highly sensitive bioindicator for ETS. Dietary
      vitamin C was determined via one 24hr recall questionnaire. When all 4 percentile
      groups were used as a basis of comparison, no differences were noted for any of
      the factors between groups, however when comparing percentile group 1 (lowest
      blood ascorbate) to an aggregate value of percentile, groups 2-4, it was found
      that vitamin C intake (corrected for energy intake) paralleled blood values with
      a statistically significant association. Among personal and environmental factors
      only exposure to ETS showed a significant difference in blood levels between
      groups 2-4 and group 1. No differences between percentile groups were noted for
      age gender or BMI. These results emphasize that ETS is strongly associated with
      lowered blood ascorbate levels with the obvious implication of reduced
      antioxidant protection and increased risk of adverse health consequences.

PMID- 17203712
TI  - Anaphylaxis: an analysis of cases evaluated at the Puerto Rico Medical Center
      over a ten-year period.
AB  - OBJECTIVE: To examine the clinical characteristics of patients with anaphylactic
      reactions evaluated at the Puerto Rico Medical Center over a ten year period.
      BACKGROUND: Anaphylaxis, an immunologic reaction classically initiated by the
      combination of an antigen and a mast cell fixed antibody (usually IgE), still
      carries a fatality rate of 500 to 1000 cases per year in the United States. It
      constitutes a medical emergency that needs to be identified promptly in order to
      install appropriate treatment. No studies of this condition have been conducted
      in Puerto Rico, specifically to assess the clinical presentation, main causes and
      outcome. METHODS: Eighty-three records of patients with a diagnosis of
      anaphylaxis were screened by retrospective and concurrent analysis. Of these,
      only 51 fulfilled the diagnostic criteria of anaphylaxis. Specific data gathered
      from those records assessed the clinical characteristics of each case,
      precipitating factors, severity of the reaction and outcome. A standard form was
      used for data gathering. A grading system was utilized to classify the severity
      of the clinical episodes. RESULTS: Cutaneous features were the most commonly
      found manifestations of anaphylactic reactions in the studied group. Only
      reactions graded 2 and 3 were identified. Reactions to medications were the most
      frequent identifiable causes of the entity. Multiple sensitivities to different
      allergens were not predictive of this clinical condition. CONCLUSIONS: The
      identification in this study that only cases with the more severe grades of
      anaphylaxis were evaluated and treated at our center, the inability to recognize
      an inciting cause in about one third of the patient sample and the fact that a
      minority of the treated patients received subsequent follow-up by an allergist,
      reflect the need to promote the training of physicians in the field of allergy in
      Puerto Rico and the continued education of all physicians in the Island regarding
      this clinical disorder.

PMID- 17203713
TI  - The economic burden of prescription drug use among elderly patients in Ponce,
      Puerto Rico.
AB  - OBJECTIVE: To examine the economic impact of prescription drug use on the
      personal income of elderly individuals in Ponce, Puerto Rico. METHODS: One
      hundred elderly individuals who attend five care centers were interviewed using a
      four-page structured questionnaire. The interview collected information about the
      source and amount of income of participants, the type of insurance coverage for
      prescription drugs, the amount of expenditures for prescription drugs that are
      paid out-of-pocket and the barriers they face to use or obtain prescription
      drugs. RESULTS: Participants were mostly female (69%) and the average age was 77
      years. The average monthly income reported was 476 dollars, 79% of which was
      derived from Social Security. The average monthly expenditure was 364.00 dollars
      of which 117.00 dollars (32%) was spent on health related expenditures: 70.00
      dollars (19%) on prescription drugs, 31.00 dollars (8%) on health insurance
      premiums, 10.00 dollars (3%) on medical expenditures not related to prescription
      drugs, and 6.00 dollars (2%) on over-the-counter drugs. The great majority
      reported having health insurance but one-third pay out-of-pocket for their
      prescription drugs. Nearly two-thirds expressed they have experienced problems to
      obtain or use medications in the past six months. Thirty-eight percent reported
      that the problem was that the cost of medications was too high. CONCLUSION: In
      spite of insurance coverage, the cost of prescription drugs places a substantial
      economic burden on elderly individuals. On average, prescription drug
      expenditures comprise nearly 20% of the personal expenditures of respondents,
      second only to groceries. This accounts for 15% of their personal income. The
      economic burden of prescription drugs on the elderly may affect access to needed
      drugs and may adversely impact health outcomes.

PMID- 17203714
TI  - Infection-associated hemophagocytic syndrome: a rare potentially fatal
      complication of systemic infection. Report of three cases.
AB  - Infection-associated hemophagocytic syndrome is a rare, potentially fatal
      complication of systemic infection. It occurs most often in immunocompromised
      patients associated with a viral infection but the spectrum of conditions have
      been broadened to include virtually every type of infectious pathogen, malignancy
      and immunosuppressive therapy. We present three pediatric patients with a similar
      clinical history of pancytopenia, hepatosplenomegaly, and acute liver failure,
      and discuss the autopsy findings.

PMID- 17203715
TI  - Primary endobronchial anaplastic large cell lymphoma in a pediatric patient.
AB  - The authors describe a pediatric patient who presented with a 3-month history of
      dry cough, chest pain, progressive breathlessness, fever and recurrent pneumonia
      with atelectasis. A fiberoptic bronchoscopy revealed a whitish lesion at the left
      bronchus. A biopsy of the lesion demonstrated an anaplastic large cell lymphoma
      (ALCL). Evaluation for disseminated disease was negative. After the patient
      completed chemotherapy the lesion abated and she has been in complete remission
      for almost 4 years. Although extranodal involvement of ALCL is frequent at some
      stage of the disease, endobronchial involvement is extremely rare even in the
      presence of advanced disease. To our knowledge, this is the first primary
      isolated endobronchial ALCL described in a pediatric patient.

PMID- 17203716
TI  - A multidisciplinary approach to surgical management of placenta previa percreta
      with bladder invasion: a case report.
AB  - Placenta previa percreta with bladder invasion occurs rarely. However this
      disorder has become more common since the increased rate of cesarean deliveries.
      We present a 26 year old gravida 3, para 2-0-1-2 female with placenta previa,
      percreta and bladder invasion to stress out the importance of early recognition
      of this life threatening condition and to point out that the good outcome of this
      case was mainly due to the multidisciplinary approach chosen during the
      preoperative and post operative management. The Departments of Obstetrics and
      Gynecology, Radiology, Anesthesiology, Urology, Neonatology and Pathology were
      fully involved. A surgical management was chosen since it is the most common and
      more accepted treatment of placenta previa percreta with bladder invasion.

PMID- 17203717
TI  - The continuing challenge of obesity.

PMID- 17203719
TI  - Can households earning minimum wage in Nova Scotia afford a nutritious diet?
AB  - OBJECTIVE: To assess the affordability of a nutritious diet for households
      earning minimum wage in Nova Scotia. METHODS: Food costing data were collected in
      43 randomly selected grocery stores throughout NS in 2002 using the National
      Nutritious Food Basket (NNFB). To estimate the affordability of a nutritious diet
      for households earning minimum wage, average monthly costs for essential expenses
      were subtracted from overall income to see if enough money remained for the cost
      of the NNFB. This was calculated for three types of household: 1) two parents and
      two children; 2) lone parent and two children; and 3) single male. Calculations
      were also made for the proposed 2006 minimum wage increase with expenses adjusted
      using the Consumer Price Index (CPI). RESULTS: The monthly cost of the NNFB
      priced in 2002 for the three types of household was 572.90 dollars, 351.68
      dollars, and 198.73 dollars, respectively. Put into the context of basic living,
      these data showed that Nova Scotians relying on minimum wage could not afford to
      purchase a nutritious diet and meet their basic needs, placing their health at
      risk. These basic expenses do not include other routine costs, such as personal
      hygiene products, household and laundry cleaners, and prescriptions and costs
      associated with physical activity, education or savings for unexpected expenses.
      CONCLUSION: People working at minimum wage in Nova Scotia have not had adequate
      income to meet basic needs, including a nutritious diet. The 2006 increase in
      minimum wage to 7.15 dollars/hr is inadequate to ensure that Nova Scotians
      working at minimum wage are able to meet these basic needs. Wage increases and
      supplements, along with supports for expenses such as childcare and
      transportation, are indicated to address this public health problem.

PMID- 17203720
TI  - Health disparity by neighbourhood income.
AB  - BACKGROUND: Canadian cities are becoming more segregated by income. As such,
      investigation is required into the magnitude of health disparity between low-,
      average- and high-income neighbourhoods in order to quantify the level of health
      disparity at the scale of an urban city. METHODS: A cross-sectional ecological
      study design was used to review all hospital discharges, physician visits,
      medication utilization, public health information and vital statistics for an
      entire city by neighbourhood income status. Postal code information was used to
      identify six existing contiguous residential neighbourhoods in the city of
      Saskatoon that were defined as low-income cut-off neighbourhoods (N=1 8,228).
      There were two comparison groups: all other Saskatoon residents (N=184,284) and
      the five most affluent neighbourhoods in Saskatoon (N=1 6,683). FINDINGS:
      Statistically significant differences in health care utilization by neighbourhood
      income status were observed for suicide attempts, mental disorders, injuries and
      poisonings, diabetes, chronic obstructive pulmonary disease, coronary heart
      disease, chlamydia, gonorrhea, hepatitis C, teen birth, low birthweight, infant
      mortality and all-cause mortality. The rate ratios increased in size when
      comparing low-income neighbourhoods to high-income neighbourhoods. No clear trend
      was observed for stroke or cancer.

PMID- 17203721
TI  - The health of single fathers: demographic, economic and social correlates.
AB  - BACKGROUND: The proportion of families headed by single fathers is increasing in
      many developed countries. The purpose of the present study was to examine the
      impact of single parenting on the self-rated health of Canadian fathers living
      with children, and the extent to which this relationship can be explained by
      social, demographic, and economic factors. METHODS: Secondary analysis of data
      from a national community health survey. The sample studied consists of 15,662
      Canadian men aged 15-64, living with at least one child under the age of 25.
      RESULTS: Compared to partnered fathers, single fathers had poorer self-rated
      health. The relationship between partner status and self-rated health could be
      completely explained by single fathers' older age, lower income, and higher rate
      of unemployment. CONCLUSIONS: Single fathers experience poorer perceived health.
      This effect appears to result from the economic and social disadvantage
      associated with raising children alone rather than from single parenting in and
      of itself. These findings, in combination with previous research, suggest a need
      for provincial and federal policies to target the well-being of both single
      mothers and single fathers.

PMID- 17203722
TI  - Youth homelessness: a call for partnerships between research and policy.
AB  - Homeless youth present significant challenges both to youth workers and policy
      makers seeking to develop better prevention and intervention strategies. This
      article discusses the compelling need for researchers and policy-makers to make
      efforts to work collaboratively to develop improved social policy informed by
      research findings.

PMID- 17203723
TI  - Engaging youth about gambling using the internet: The YouthBet.net website.
AB  - OBJECTIVE: YouthBet.net's (www.youthbet.net) goal is to prevent gambling problems
      among youth through an interactive, multimedia website based on a public health
      approach. PARTICIPANTS: YouthBet.net was designed by youth for youth. A youth
      working group spent several months designing the look and feel of the site to
      ensure that it would appeal to youth aged 10-19. In total, 34 youth from the
      Greater Toronto Area participated in the first 3 phases of the usability testing
      of the site using Video Capture of User Site Interaction methodology. SETTING:
      Urban Toronto. INTERVENTION: Utilizing public health strategies such as health
      promotion, harm reduction and problem prevention, YouthBet.net features games,
      information and help resources to protect youth from gambling-related harm.
      OUTCOMES: Youth participants indicated that they liked the interactive way
      gambling information was presented via realistic games and quizzes, often citing
      that YouthBet.net would be a fun and educational tool to be used by teachers in
      the classroom. Participants had no difficulties navigating the site, finding
      content and playing games. Additionally, all youth said that they would return to
      the site and would recommend it to a friend if they were having a problem with
      gambling. CONCLUSION: YouthBet.net is one of the first comprehensive websites
      designed for youth gambling. Findings from this research will inform future
      health promotion, harm reduction and problem prevention efforts for youth
      gambling using Internet technology.

PMID- 17203725
TI  - Pertussis in rural populations of Saskatchewan (1995 to 2003): incidence,
      seasonality, and differences among cases.
AB  - BACKGROUND: Few Canadian studies have studied re-emergent pertussis in rural
      areas. This study described the epidemiology of pertussis in the rural areas of
      the Saskatoon Regional Health Authority in Saskatchewan, and comparisons were
      made to the City of Saskatoon. METHODS: Analyses were based on passive
      surveillance data collected between 1995 and 2003. Estimates of the cumulative
      incidence (per 10,000 population) measured the occurrence of pertussis. Kaplan
      Meier curves were plotted to compare a case's time until disease from their last
      vaccination by different vaccine types (whole-cell (WCV), or acellular (ACV)) and
      vaccine histories (complete or partial). Epidemic curves identified peaks in the
      incidence and checked for seasonal variation in case reporting. RESULTS: Over the
      9-year period, 1,135 cases were reported. Rural areas had higher incidence rates
      and lower proportions of cases vaccinated than urban areas. Overall, the highest
      age-specific incidence was observed in people aged 10-19 years. Cases aged 0-9
      years vaccinated with the ACV, from both rural and urban areas, presented a
      shorter time to disease (14 months (95% CI: 13-16) and 17 months (95% CI: 11-21),
      respectively) when compared to cases vaccinated with the WCV (47 months (95% CI:
      40-51) and 36 months (95% CI: 31-41), respectively), or with a combination of the
      two vaccines (40 months (95% CI: 27-47) and 44 months (95% CI: 36-51),
      respectively, p<0.01). Epidemic curves revealed that reported cases are occurring
      earlier in successive years (1997, 1999, and 2003) in rural areas. CONCLUSION:
      Epidemiologic differences among cases from rural areas exist when compared to
      urban areas. This study further emphasizes the need to better understand age-,
      vaccine-, and seasonally-related aspects of pertussis epidemiology in rural
      areas.

PMID- 17203724
TI  - What is the evidence for parenting interventions offered in a Canadian community?
AB  - BACKGROUND: The evidence supporting interventions offered in the community is
      often not examined. This study examines the evidence base supporting parenting
      interventions offered in a Canadian community and, in so doing, illustrates a
      community assessment mechanism that could be applied routinely for other
      psychosocial interventions. METHODS: An inventory of all manual-guided, group
      based parenting interventions offered in a moderate-sized Canadian city was
      developed by reviewing existing community information guides and contacting key
      providers of parenting programs. Interventions offered between July 1, 2000 and
      June 30, 2001 were selected for evaluation. Evaluation reports for each
      intervention were assessed by two independent raters using a modification of the
      Effective Public Health Practice Project Quality Assessment Tool. RESULTS: Twelve
      parenting interventions were offered in the study community. Only three (25%) had
      been evaluated with at least one randomized controlled trial. No evaluation
      identified an a priori primary outcome measure to assess effectiveness. Multiple
      statistical testing without including a correction factor limits confidence in
      the robustness of the small number of positive results. Under-powered evaluations
      were common. Three interventions had only post-intervention client satisfaction
      data. The study community used none of the existing parenting interventions that
      are supported by extensive empirical evidence of efficacy. INTERPRETATION: There
      is a substantial research-practice gap in the parenting interventions offered in
      the study community. Similar community assessments could be used to spur debates
      within other communities about how best to reduce the research-practice gap.

PMID- 17203726
TI  - Juggling demands: Canadian health aid to Latin America since World War II.
AB  - BACKGROUND: Since the development of the Commonwealth's 1950 Colombo Plan
      (Canada's first official aid program), health-related development assistance has
      been an important instrument of Canadian foreign policy, allowing it to gain a
      presence in a range of countries and help to shape international affairs. This
      pattern is evident in the history of Canadian multilateral and bilateral health
      aid to Latin America. METHODS: This analysis draws on historical material from
      the Departments of External Affairs and National Health and Welfare held at the
      Library and National Archives of Canada regarding Canadian involvement with the
      Pan American Health Organization (PAHO), and program information from the
      Canadian International Development Agency's (CIDA) Corporate Reporting Services
      Group. FINDINGS: Canada was initially a tentative player in the region. However,
      as Canadian foreign policy interests shifted towards the region in the 1970s,
      Canada used both multilateral and bilateral health aid to establish a presence in
      Latin America that was independent from, yet unthreatening to, United States
      hegemony in the region. CONCLUSION: The impact of Canada's provision of health
      aid to Latin America via PAHO and CIDA has been largely symbolic, allowing Canada
      to pursue an independent foreign policy in the region and to foster a positive
      international image for itself with minimal spending.

PMID- 17203727
TI  - Canada's International Development Research Centre's eco-health projects with
      Latin Americans: origins, development and challenges.
AB  - BACKGROUND: Since its founding in 1970, Canada's International Development
      Research Centre (IDRC) has supported research by concerned Latin American
      researchers on environments and human health relationships. Framing of such
      relationships has changed through different periods. METHODS: Participant
      observation, bibliographic searches, document review, and interviews with key
      IDRC staff. FINDINGS: From the early years of multiple different projects, IDRC
      developed more focussed interest in tropical diseases, pesticides, agriculture
      and human health in the 1980s. The United Nations Conference on Sustainable
      Development in the early 1990s gave impetus to examination of links between
      ecosystems and human health or "EcoHealth". Projects in Latin America built on
      earlier work but extended it in methods (transdisciplinarity, community
      participation, gendered approach) and scope (broader land use and development
      paradigm issues tackled). A key IDRC-funded activity in Latin America was
      "EcoSalud", an Ecuadorian effort, which has worked with farming communities,
      agricultural researchers, health practitioners and local politicians to advance
      integrated pest management, better recognize and treat poisonings and improve
      pesticide-related policies. ONGOING CHALLENGES INCLUDE: mobilizing sufficient
      resources for the primary prevention focus of EcoHealth activities when primary
      care infrastructure remains stretched, promoting micro-level change in diverse
      communities and ecosystems, and addressing power structures at the global level
      that profoundly affect environmental change.

PMID- 17203728
TI  - Expanding drug access in Brazil: lessons for Latin America and Canada.
AB  - This paper discusses Brazil's efforts to provide essential medicines for its
      population while meeting international trade obligations. In the 1950s and 1960s,
      Brazil's pharmaceutical industry was largely overtaken by foreign companies. To
      counteract this, Brazil enacted a law in 1971 that allowed the production of
      patented drugs in order to provide affordable medicines, encourage research and
      development, and reduce dependency on imports. Eventually, pressure from the
      United States government (through tariffs and sanctions) drove Brazil to
      introduce pharmaceutical patent laws. Local interests prevailed, however, through
      Brazil's liberal interpretation of the TRIPS Agreement, which included a
      provision that pharmaceutical products must be "worked" or manufactured locally
      or the government could turn to the use of compulsory licensing. Brazil's
      willingness to use the threat of compulsory licensing compelled drug companies to
      lower HIV/AIDS drug prices substantially. Finally, the paper discusses how Canada
      can facilitate improving drug access in Latin America through helping Brazil
      expand its role as a manufacturer and providing medicines to countries without
      manufacturing capabilities.

PMID- 17203729
TI  - Challenging the neoliberal trend: the Venezuelan health care reform alternative.
AB  - Throughout the 1990s, all Latin American countries but Cuba implemented to
      varying degrees health care sector reforms underpinned by a neoliberal paradigm
      that redefined health care as less of a social right and more of a market
      commodity. These health care sector reforms were couched in the broader
      structural adjustment of Latin American welfare states prescribed consistently by
      international financial institutions since the mid-1980s. However, since 2003,
      Venezuela has been developing an alternative to this neoliberal trend through its
      health care reform program called Mision Barrio Adentro (Inside the
      Neighbourhood). In this article, we introduce Mision Barrio Adentro in its
      historical, political, and economic contexts. We begin by analyzing Latin
      American neoliberal health sector reforms in their political economic context,
      with a focus on Venezuela. The analysis reveals that the major beneficiaries of
      both broader structural adjustment of Latin American welfare states and
      neoliberal health reforms have been transnational capital interests and domestic
      Latin American elites. We then provide a detailed description of Mision Barrio
      Adentro as a challenge to neoliberalism in health care in its political economic
      context, noting the role played in its development by popular resistance to
      neoliberalism and the unique international cooperation model upon which it is
      based. Finally, we suggest that the Venezuelan experience may offer valuable
      lessons not only to other low- to middle-income countries, but also to countries
      such as Canada.

PMID- 17203730
TI  - Enhanced surveillance for adverse events following immunization: Two years of
      dTap catch-up among high school students in Yukon, Canada (2004, 2005).
AB  - BACKGROUND: To address the increasing age of pertussis cases, Yukon replaced the
      Grade 9 tetanus/diphtheria/inactivated polio booster with
      diphtheria/tetanus/acellular pertussis (dTap) and implemented a dTap catch-up
      program for Grade 12 students. The program began in June 2004, making Yukon one
      of the first Canadian jurisdictions to introduce dTap within five years of a
      tetanus booster. We implemented enhanced surveillance to monitor adverse events
      following immunization (AEFI) to determine whether students receiving dTap > or
      =3 to <5 years after their last tetanus booster were at increased risk of severe
      AEFI. METHODS: Students completed a self-administered AEFI questionnaire one week
      post-dTap vaccination. Public health professionals contacted students reporting
      severe AEFI. Health care providers were requested to report AEFI. Symptom rate,
      severity and duration were compared between students receiving dTap > or =3 to <5
      years after their last tetanus booster and those receiving it >5 years later.
      RESULTS: The > or =3 to <5 years group was more likely than the > or =5 years
      group to report pain at the injection site (70.6% vs. 61.5%, p=0.038) and less
      likely to report injection site redness (10.0% vs. 17.3%, p=0.022), injection
      site swelling (8.9% vs. 16.4%, p=0.013), decreased energy (10.0% vs. 17.1%,
      p=0.023), body aches (2.2% vs. 7.2%, p=0.014) and sore joints (3.3% vs. 10.1%,
      p=0.004). Severe AEFI did not differ between the groups (3.3% vs. 5.6%, p=0.232).
      Health care professionals reported no AEFI. CONCLUSIONS: Results suggest no
      increased risk of severe AEFI among students receiving dTap > or =3 to <5 years
      after their last tetanus booster.

PMID- 17203731
TI  - Regional, seasonal, and antimicrobial resistance distributions of salmonella
      typhimurium in Canada: a multi-provincial study.
AB  - BACKGROUND: This study was conducted to describe the geographical and seasonal
      distributions of reported human Salmonella Typhimurium (ST) definitive type 104
      (DT104) cases, to compare these characteristics to those of non-DT1 04 cases, and
      to investigate specific antimicrobial resistance (AMR) patterns in four Canadian
      provinces. METHODS: All laboratory-confirmed ST cases originating from passive
      reporting in Alberta, British Columbia, and Saskatchewan, and every second case
      in Ontario identified from December 1999 through November 2000 were investigated.
      RESULTS: A total of 470 human Salmonella Typhimurium cases were identified during
      the study period. DT104 was the most common phage type, although its incidence
      varied by province. The proportion of DT104 cases living in urban Ontario,
      British Columbia and Saskatchewan did not differ from the general population, but
      in Alberta, the DT104 cases were more likely to live in rural areas. Overall,
      DT104 isolates were more often R-type ACSSuT compared to non-DT104 cases, and R
      type AKSSuT was often associated with DT208. DT104 cases displayed no seasonality
      whereas non-DT104 cases were more frequent in the summer than in the winter.
      INTERPRETATION: Our results suggest that DT104 and non-DT104 cases vary by
      province, urban vs. rural residential status and by resistance patterns. Lack of
      seasonality in the DT104 cases may indicate a lesser influence of the agro
      environmental route (i.e., farm -manure - water and direct contact) compared to
      the agro-food route (i.e., farm - animals -food) for these infections. Strain
      characterization and integration of surveillance information related to ST from
      animal, food and humans is warranted.

PMID- 17203732
TI  - A process evaluation of an intervention to improve respiratory infection control
      practices in family physician offices.
AB  - OBJECTIVE: To conduct a process evaluation of a short-term intervention by public
      nurses for physicians to facilitate the incorporation of new respiratory
      infection control practices in physicians' offices. DESIGN: Process evaluation.
      SETTING: Family physician offices in Ottawa, Ontario, Canada. PARTICIPANTS: Five
      public health nurse-facilitators and 53 primary care practices including 143
      family physicians. METHOD: Effectiveness of facilitator training assessed by self
      administered questionnaires. Data assessing process of facilitation collected
      through activity logs and narrative reports. Physicians' satisfaction assessed by
      post-intervention questionnaire. MAIN FINDINGS: Facilitators reported that
      training strongly contributed to their knowledge and skills and all were either
      satisfied or highly satisfied with their facilitation training. All practices
      received at least two visits by the facilitator and more than half (51%) were
      visited three or more times. Facilitators identified the provision of the
      evidence-based Tool Kit and consensus-building with office staff as key factors
      contributing to the intervention's success. Of the 45% of physicians who
      completed the questionnaire (65/143), only 5% reported being somewhat
      dissatisfied with the intervention, 11% reported the visits were not frequent
      enough, and 9% thought the visits were too close together. The majority (97%)
      felt the facilitation program should be available to all family physicians and
      98% would continue to use the service if available. CONCLUSIONS: It is feasible
      for public health nurses to be trained in outreach facilitation to improve
      respiratory infection control practices in physicians' offices and this has been
      widely appreciated by physicians. This model of public health/primary care
      collaboration deserves further exploration.

PMID- 17203733
TI  - [Productivity and practice profiles of general practitioners in Tirana, Albania].
AB  - BACKGROUND: Albania, as with all Central and Eastern European countries whose
      health systems were highly centralized, has undertaken a number of reforms aiming
      to transform, among many items, the financing and delivery of primary health care
      services. OBJECTIVE: This study assesses the practice activities of general
      practitioners working in the region of Tirana, over a period of 12 months.
      METHODS: Production is measured by the number of monthly visits carried out by
      the practitioner, and practice profiles are determined by referral rates for
      specialist care and prescription rates per visit. Multi-level regression
      analyses, taking into account the hierarchical structure of the data, were
      performed to identify the factors associated with productivity and profiles of
      practice. RESULTS: Results show large urban-rural variations with respect to
      practice conditions, characteristics of practitioners, productivity, and profiles
      of practice. Productivity was weak in the city of Tirana (an average of 277
      monthly visits), 18% of patients were referred to specialists, and 66% received
      prescriptions. In rural areas, productivity was weaker (an average of 179 monthly
      visits), referral rates were lower (11%), and the prescription rate was 74%. In
      urban and rural areas, productivity and profiles of practice were related to the
      characteristics of both the client and the health centre and to the type of
      practice. CONCLUSION: There are only a few available epidemiological studies
      documenting the ongoing health transition and the concomitant increase in demand
      for primary health care services; therefore, we are unable to (causally) link the
      reported low productivity of general practitioners with population needs.
      Physician productivity and patient care is better for certain groups and in
      health care settings where a wide range of services and sophisticated medical
      technologies are available. The capacity to efficiently plan for medical manpower
      is limited - this may be attributed to deficiencies of the patient registration
      system on the lists of physicians who are paid on the basis of capitation.
      Additional studies examining utilization of health services, and satisfaction of
      patients and providers, is needed in order to provide sound recommendations for
      improving Albania's health care system.

PMID- 17203734
TI  - Hepatitis C, illicit drug use and public health: does Canada really have a viable
      plan?
AB  - Some 300,000 individuals are infected with the hepatitis C virus (HCV) in Canada.
      HCV infection is associated with major morbidity, mortality and health care
      costs; these indicators are projected to rise over the next decade. The vast
      majority of prevalent and incident HCV infections in Canada are illicit drug use
      related; thus, the HCV disease burden can only be addressed through interventions
      targeting this primary risk factor. Both preventive (e.g., needle exchange,
      methadone treatment) and therapeutic (e.g., the accessibility of HCV treatment
      for illicit drug users) interventions aimed at HCV in illicit drug users have
      been broadly expanded in Canada in recent years. However, evidence suggests that
      existing preventive measures only offer limited effectiveness in reducing HCV
      risk exposure. Also, due to restricted resources, treatment for HCV currently
      only reaches an extremely small proportion (i.e., <5%) of HCV-infected drug
      users. Thus, on the basis of current HCV incidence as well as given interventions
      and their impact, Canada is not achieving a net reduction in the prevalence of
      HCV-related to illicit drug use. In order to reduce the HCV disease burden,
      Canada needs to reconsider the scope, delivery and resourcing of both preventive
      and treatment interventions targeting the primary risk population of illicit drug
      users.

PMID- 17203735
TI  - Factors associated with the use of over-the-counter medications in cases of acute
      gastroenteritis in Hamilton, Ontario.
AB  - BACKGROUND: Monitoring over-the-counter (OTC) medication sales may provide an
      accurate, reliable way to observe trends and detect aberrations in community
      health status. This study assessed demographic and symptomatic factors associated
      with the use of OTC anti-nauseants (AN), anti-diarrheals (AD), and rehydration
      therapies (RT) in cases of acute gastroenteritis (GE). METHODS: Data on 351 cases
      of self-reported, acute GE obtained from a population-based telephone survey were
      analyzed. The four outcomes of interest were use of an OTC 1) AD, 2) AN, 3) RT,
      and 4) use of at least one of the three. The association between each factor of
      interest and the use of OTC treatments was assessed. RESULTS: Of the 351 cases,
      110 (31%) used at least one OTC AD, AN, or RT for their illness. The most
      significantly associated factor was primary symptom group: cases with both
      vomiting and diarrhea were 3.6 times more likely to use at least one of the three
      OTC medications than cases with either vomiting or diarrhea only. Other factors
      associated with the use of at least one OTC were being female (OR=1.97), being 10
      14 years of age iOR=l 1.22), and use of antacids in the 28 days prior to illness
      (OR=2.31). CONCLUSION: This study provides the first published assessment of
      factors associated with the use of OTC medications by community cases of GE.
      Those who use OTC medications for their illness appear to differ from those who
      do not. This information can inform health officials, and aid development of
      pharmacy-based syndromic surveillance.

PMID- 17203736
TI  - Experience in many venues of nursing.

PMID- 17203737
TI  - Isolation and partial characterization of bovine foamy virus from Polish cattle.
AB  - The first isolation and partial characterization of bovine foamy virus (BFV),
      also known as bovine syncytial virus, in Poland is described. This virus was
      isolated by co-cultivation of peripheral blood leukocytes from infected cattle
      with permissive Cf2Th cells. The new isolate, called BFV100 was identified using
      several techniques: electron microscopy, western blotting, PCR and sequencing of
      a part of the gag and pol/env genes. Based on syncytia induction, antigenic
      determinants, primer binding sites and sequence analysis, it can be concluded
      that isolate BFV100 is bovine foamy virus and is related to the known American
      and German BFV isolates by sequence homology and antigenic relatedness.

PMID- 17203738
TI  - Application of PCR technique in diagnosis of small ruminant lentivirus infection
      in sheep and goats.
AB  - Detection of small ruminant lentiviruses (SRLVs) in sheep and goats usually
      relies on serological testing. In this study, we evaluated semi-nested PCR and
      nested PCR techniques applied as a diagnostic tool for detection of maedi-visna
      virus (MVV) and caprine arthritis-encephalitis virus (CAEV) in naturally infected
      sheep and goats, respectively. The examination of 193 ovine and 85 caprine serum
      samples by the ELISA revealed the presence of specific antibodies in 133 (69%)
      and 18 (21.2%) animals, respectively. Presence of proviral DNA was manifested in
      103 (53.4%) sheep and 12 (14.2%) goats. Despite the relatively lower sensitivity
      of PCR, the fact of detection of proviral DNA in 19 out of 60 ovine samples and 7
      out of 67 caprine samples collected from animals previously negative by ELISA was
      noteworthy. In conclusion, the data demonstrated that combinations of both ELISA
      and PCR might afford optimal detection of SRLVs infection.

PMID- 17203739
TI  - The influence of boar pheromones on the vasoreactivity of the facial superficial
      veins in ovariectomized and estradiol-treated pubertal gilts.
AB  - This study was designed to establish: a) whether boar pheromones, androstenone
      and androstenol, may affect the vasocontractility of the facial superficial veins
      in ovariectomized pubertal gilts and b) what is the effect of estradiol on this
      contractility. The gilts ovariectomized after two controlled estrous cycles, and
      the ovariectomized gilts treated with estradiol benzoate were used in the
      experiment. The isolated rings of dorsal nasal, frontal and facial veins were
      incubated with androstenone (5alpha-androst-16-en-3-one) and androstenol (5alpha
      androst-16-en-3-ol) in concentrations of either 1 or 10 microM. Changes in the
      contractile activity of the isolated vein segments were measured using isometric
      transducer and recorded with HSE-ACAD W software. In ovariectomized gilts both
      the androstenone and androstenol caused a relaxing effect on the nasal vein, flow
      of the blood from the nasal cavity, and on the frontal vein, by which the blood
      may by directed into the perihypophyseal vascular complex. An opposing reaction
      to these pheromones was found in the distal part of the facial vein by which the
      blood is directed to the systemic circulation. Treating ovariectomized gilts with
      estradiol benzoate changed mainly the reactivity of the frontal vein to
      androstenone, which produces constriction, but this treatment did not affect the
      reactivity of the facial superficial veins to androstenol. The present results
      demonstrated that both boar sex pheromones, androstenone and androstenol, may
      contribute to the regulation of their humoral pathway from the nasal cavity to
      the brain and hypophysis in the ovariectomized pubertal gilts and suggest the
      effect of estradiol to this pathway.

PMID- 17203740
TI  - The level of serum ionised calcium, aspartate aminotransferase, insulin, glucose,
      betahydroxybutyrate concentrations and blood gas parameters in cows with left
      displacement of abomasum.
AB  - The purpose of this study was to determine concentrations of serum glucose,
      aspartate aminotransferase (AST), insulin, beta-hydroxybutyrate (BOH) and ionised
      calcium (Ica) in dairy cows with left displaced abomasum (LDA) and to compare
      these parameters before and after surgical correction of LDA. Eighteen Swiss
      Holstein dairy cows with LDA were used in this study. Clinically healthy post
      parturient cows (n: 10) from a local dairy farm were used as control group. Blood
      samples were collected from the jugular vein from all the cows. Surgery was
      performed in cows with LDA. Blood samples from cows with LDA were collected 24
      hours after surgery. The abomasum was repositioned followed by an omentopexy. Six
      of the 18 cows with LDA had clinical ketosis as detected with urine dipstick. The
      mean concentrations of insulin, BOH, glucose and AST in cows with LDA at
      admission time were increased compared with the healthy cows. But the mean
      concentration of ICa at admission time was slightly decreased compared with
      healthy cows. The mean BOH concentration was decreased 24 hours following surgery
      compared with values on admission time. However, the mean serum AST levels were
      increased both at admission time and 24 hours after surgery compared with healthy
      cows. The levels of blood gas parameters in cows with LDA were not significantly
      different in comparison with healthy cows, although hyperbasemia in six of 18
      cows with LDA was determined. In conclusion, the results of this study indicated
      that serum insulin, glucose, AST and BOH levels were increased in dairy cows with
      LDA. Serum BOH and ICa levels were decreased 24 hours after surgery compared with
      values on admission time. All cows with LDA used in this study had
      subclinical/clinical ketosis. We could say that ketosis might be a risk factor
      for the displacement of the abomasum.

PMID- 17203741
TI  - Comparison of plasma biochemical parameters in Thoroughbred and Purebred Arabian
      horses during the same-intensity exercise.
AB  - The objective of the present study was to compare changes of blood parameters
      induced by the same work and performed in the same conditions in two racehorse
      breeds, Thoroughbred and Purebred Arabian. The effect of moderate-intensity
      exercise was studied in 20 stallions--ten Thoroughbreds, aged 2-3 years and the
      same number of Purebred Arabians, 3-4 years old. All the horses were
      administrated the same effort test consisting in 1200 m gallop at a speed typical
      of the daily training sessions. Three jugular venous blood samples were collected
      for each horse: at rest, just after the end of the gallop and after 30-minute
      rest. In the gathered blood, a hemoglobin (Hb) concentration was determined as
      well as plasma level of glucose (Glc), triacylglycerols (TG), glycerol, free
      fatty acids (FFA), total plasma proteins (TP) and the activity of creatine kinase
      (CK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST). In the
      Arabian horses, an increase in levels of TP, glycerol, FFA and CK activity
      measured just after exercise was higher than that in Thoroughbreds. Similarly,
      after a 30-minute rest, a post-exercise rise of TP, AST, glycerol and FFA proved
      to be higher in the Arabian horses compared to that in the Thoroughbreds. Only TG
      plasma concentration measured 30 minutes following the effort was significantly
      lower in the Arabian horses than in Thoroughbreds. It can be concluded that the
      Thoroughbred horses adapted better to the effort test applied in this study as
      compared to the Purebred Arabian horses. The parameters related to lipid
      metabolism proved to be the most sensitive indicators of breed differences in
      relation to moderate-intensity exercise.

PMID- 17203742
TI  - The effect of interferon-tau and ovarian steroids on the proliferation of bovine
      endometrial cells in vitro.
AB  - The goal of this study was to evaluate the effect of various concentrations of
      interferon-tau (IFN-tau) with or without steroid hormones, 171 estradiol or
      progesterone, on the proliferation of bovine endometrial cells in vitro.
      Endometrial epithelial and stromal cells were isolated from the uterus of cows
      during the early estrus cycle (2-3 days) and incubated with different doses of
      IFN-tau with or without steroid hormones. The proliferation was determined by the
      MTT test in 48, 96, and 144 h of incubation. An antiproliferative activity of IFN
      tau was observed both in epithelial and stromal cells cultured in RPMI 1640
      medium supplemented with 10% FBS or. serum replacement. However, epithelial cells
      were more sensitive to antiproliferative action of interferon-tau. It;s activity
      was dose-and time-dependent. The inhibition of epithelial cell proliferation by
      50% (ED50) was achieved at concentrations of 500 U/ml, 340 U/ml, and 8.8 U/ml of
      IFN-tau after 48, 96, and 144 h of incubation, respectively. None of the doses of
      IFN-tau (10-10.000 U/ml) used inhibited stromal cell proliferation in 50%. The
      most effective dose of IFN-tau inhibiting stromal cell proliferation was 10.000
      U/ml, which decreased cell growth by 17.08%, 22.87%, and 2.6% after 48, 96, and
      144 h of incubation, respectively. Steroid hormones, 17beta estradiol and
      progesterone, added to the culture of stromal cells with or without IFN-tau did
      not significantly modulate stromal cell growth. In contrast, a high concentration
      of progesterone (10(-5) M) alone significantly enhanced stromal cell growth.
      Progesterone at low, physiological concentrations (10(-7)- 10(-9) M) ameliorated
      the antiproliferative activity of IFN-tau, especially at the 10(-9 )M
      concentration. At this concentration, the stimulatory effect on stromal cell
      growth was observed. The mechanisms of such response are not entirely clear but
      may arise from the influence of IFN-tau on progesterone down regulation of its
      own receptor. Depicted activity of IFN-tau may find usefulness in therapy of
      neoplastic disorders.

PMID- 17203743
TI  - The impact of zearalenone on the level of the selected estrogens in blood serum
      of sexually immature gilts.
AB  - The aim of the study was to evaluate the influence of low dose (LOEL - lowest
      observed effect level) of zearalenone (200 microg/kg b.w.), applied per os for 7
      days (short-term intoxication), on sexual behavior, concentration of the examined
      xenobiotic and its metabolite and selected estrogens in sexually immature gilts:
      ovariohysterectomised (group D1) and intact (group D2) animals. Clinical signs of
      oestrus (reddening, oedema and hyperaemia of the vulva and serorhoea from the
      reproductive tract--lack of standing reflex) were obserwed in group D1 on day 6
      and in group D2 on day 4 of the experiment. Laboratory analyses of blood plasma
      were carried out determine the presence of zearalenone and alpha-zearalenole.
      They revealed an increase in the level of alpha-zearalenol before the oestrus,
      decrease in total amount of both examined substances on day when the oestrus
      appeared and increase in the level of both examined xenobiotics in the post
      oestrus period together with the higher share of zearalenone. Medium
      concentrations of estrone and estradiol within the borders of method
      determination in the majority of periods examined. Higher levels of estrone (32.0
      pg/ml) were found on day 4, in the group D2 and estradiol (6.5 pg/ml) on day 6 in
      the D2 group. The presents study revealed that zearalenone applied per os at LOEL
      dose causes the incidence of apparent sexual readiness (without standing reflex)
      in sexually immature gilts with the somatically immature reproductive system.

PMID- 17203744
TI  - Thyroid hormones concentrations and ECG picture in the dog.
AB  - Disorders of the thyroid gland activity are the most commonly encountered
      disturbances of endocrine origin in the dog. Hypo- or hyperthyroidism may disturb
      the function of the cardiovascular system and cause arrhythmias. The aim of this
      study was to evaluate the influence of thyroid gland activity on
      electrocardiogram (ECG) picture in the dog by comparing ECG curves of healthy
      dogs, dogs with hypothyroidism and dogs with cardiac insufficiency caused by
      endocardiosis of the mitral valve. The study was performed on 38 dogs, patients
      of the Department of Internal and Parasitic Diseases with Clinic for Horses, Dogs
      and Cats in Wroclaw. The animals were assigned to 3 groups: Group I--control
      group, 13 clinically healthy dogs; Group II--14 dogs with diagnosed cardiac
      insufficiency caused by endocardiosis of the mitral valve; Group III--11 dogs
      with hypothyroidism. Clinical examination of the animals was conducted according
      to the following pattern: anamnesis, general clinical examination, cardiological
      examination (ECG, USG of the heart) and laboratory analysis (triacylglycerydes,
      cholesterol, T3, T4, FT4). In this study, the significant influence of thyroid
      gland activity on ECG picture of the evaluated dogs was found. In the dogs with
      hypothyroidism a decrease in the sino-atrial node activity was observed, which
      led to decreased heart rate. In dogs with hypothyroidism, the innerheart
      conduction was reduced, which was demonstrated by prolongation of the P wave, QRS
      complex and the QT interval.

PMID- 17203745
TI  - Twins rate in the black-and-white cattle population in Lithuania.
AB  - Obtaining the maximal number of calves from each cow according to its natural
      genetic reproduction ability is the main condition of intensification of
      reproduction and increase of milk production. Twins rate in the black-and-white
      cattle population in Lithuania is 2.4%. Cows whose mothers have calved twins at
      least 1 time during reproductive life have twins in 5.6% of all calvings, the
      others--in 1.9%. Twins rate in separate bulls daughters range from 1% to 6.1%.
      Twins rate in cows range from 0.4% to 5% by separate bulls-getters. Productivity
      of 305 days lactation after having twins is better (551.2+/-68.1 kg of milk, 18.4
      +/-2.9 kg of fat and 21.5+/-2.4 kg of protein, P < 0.001). The rate of twin
      births increases when lactation is increased. The influence of lactation on rate
      of twin births is 0.6% in total dispersion (P < 0.001). The influence of calving
      season on twins rate is statistically insignificant but the parts of twins by
      calving seasons are distributed differently.

PMID- 17203746
TI  - Conglutinin, CL-43 and CL-46--three bovine collectins.
AB  - Conglutinin, collectin-43 (CL-43) and collectin-46 (CL-46) are serum proteins
      characteristic for Bovidae. They belong to collectins--family of oligomeric
      proteins composed of trimeric subunits containing collagen-like sequences joined
      to C-type lectin domains. The genes encoding conglutinin, CL-43 and CL-46 are
      located on the bovine chromosome 28, and phylogenetic analysis indicates their
      common origin--from the lung surfactant protein D gene. Northern blot or
      immunocytochemical analysis confirm biosynthesis of bovine collectins mainly in
      the liver (conglutinin, CL-43) and in the thymus (CL-46). The level of
      conglutinin in the serum of dairy cows depends on many factors such as breeding,
      the season of the year, the stage of the reproductive cycle and infection. The
      collectins are involved in the innate immune defense. They bind to microbial
      surface carbohydrates inducing aggregation and, thereby, impeding infectivity. On
      the other hand the destruction of pathogens occurs due to stimulation of effector
      cells. CL-43 as well as conglutinin, binds to the collectin receptor (C1qR)
      localized on many types of cells identified as a surface variant of calreticulin.
      Conglutinin and CL-43 show antiviral activities towards influenza A virus and
      rotaviruses. Conglutinin also displays protective activity against bacterial
      infections.

PMID- 17203747
TI  - Hyperthermia and immunity. A brief overview.
AB  - After many years, hyperthermia (HT) is experiencing a new resurgence as seen by
      the positive results of many randomized trials all over the world. Tumour
      immunity similarly is suggested as the fourth modality of therapy for metastatic
      tumours from renal carcinoma and melanoma. An overwhelming amount of data from
      animal models and human patients indicate that whole body and locoregional
      hyperthermia exerts many biological and therapeutic effects on immune competent
      cells and cytokines. Among these effects, hyperthermia has recently been
      demonstrated to enhance the antigen presentation and consequently the activity of
      dendritic cells. This improvement is obtained through several mechanisms: a)
      increased lymphocyte recruitment and trafficking into the tumour area; b)
      increased immunogenicity of heat treated tumour cells; and c) increased
      production of the heat-shock proteins and costimulatory molecules. The effects
      and mechanisms of HT on immunity, lymphocyte recruitment and dendritic cell
      stimulation by heat shock proteins are reviewed here. Moreover the use of HT as
      an innate immunity booster in association with biological response modifiers is
      suggested.

PMID- 17203748
TI  - Anticancer drug delivery with nanoparticles.
AB  - Nanotechnology provides a variety of nanoscale tools for medicine. Among them
      nanoparticles are revolutionizing the field of drug delivery. These drug
      nanocarriers have the potential to enhance the therapeutic efficacy of a drug,
      since they can be engineered to modulate the release and the stability and to
      prolong the circulation time of a drug, protecting it from elimination by
      phagocytic cells or premature degradation. Moreover, nanoscale carriers can be
      tailored to accumulate in tumour cells and tissues, due to enhanced permeability
      and a retention effect or by active targeting using ligands designed to recognize
      tumour-associated antigens. Could these nanomedicine tools mark an end to the
      necessity for loco-regional drug delivery?

PMID- 17203749
TI  - Tubular dysfunction after peritonectomy and chemohyperthermic treatment with
      cisplatin.
AB  - Peritoneal carcinomatosis has always been regarded as a contraindication in
      traditional cancer surgery treatment; however, good results have been reported by
      using new combined medical-surgical loco-regional techniques. Peritonectomy and
      chemohyperthermic perfusion with cisplatinum (CIIP) seem to play a central role
      in obtaining a better survival rate than with the traditional procedures, even
      though there is a cisplatinum nephrotoxic effect. The aim of this study was to
      investigate entity and type of renal injury after CIIP. Forty-two patients (12
      males and 30 females) with recurrent or primary peritoneal carcinomatosis who
      underwent peritonectomy and cytoreductive surgery with hyperthermic
      intraperitoneal chemotherapy with cisplatin were enrolled. A significant
      worsening in renal function was observed on the third post-operative day and this
      condition then persisted for three months. A reduction in estimated-Glomerular
      Filtration Rate (e-GFR) and an alteration in the albumin:creatinine ratio proved
      tubular injury. On the third post-operative day after cisplatinum administration,
      a high toxicity peak was found following platinum free fraction excretion.
      Proximal tubular injury was confirmed even at the three month analysis. A
      significant correlation between the total protein reduction rate and the decrease
      in renal function was established. In relation to that, the platinum free
      fraction could increase because of a binding protein shortage and the nephrotoxic
      effect could be enhanced due to platinum accumulation within the post-operative
      period. This finding suggests that the higher the protein reduction is, the lower
      the e-GFR determination is at three months.

PMID- 17203750
TI  - Hepatic arterial chemotherapy in combination with systemic chemotherapy compared
      with hepatic arterial chemotherapy alone for liver metastases from colorectal
      cancer: results of a multi-centric randomized study.
AB  - Hepatic arterial infusion (HAI) chemotherapy is accepted to be an option in
      patients with non-resectable metastases from colorectal cancer confined to the
      liver. In a multi-istitutional trial, 76 patients were randomly assigned to
      receive HAI versus HAI plus systemic bolus 5-fluorouracil and leucovorin. The
      primary endpoint was survival, followed by response, recurrence and toxicity.
      Survival was longer for HAI plus systemic chemotherapy (HAI+SYC) than HAI
      (median, 20 vs. 14 months; p = 0.0033), as were responses (47.5% and 41.7%; p =
      0.09) and time to hepatic progression (12 vs. 8 months; p = 0.039). Side effects
      included haematological toxicity that was mostly mild and reversible in 432
      cases. Neutropenia grade 3 occurred in four patients in the HAI+SYC arm and one
      in the HAI arm. Diarrhoea occurred in 20% and 7% of patients and stomatitis
      occurred in 18% and 2%, respectively. On the contrary biliary toxicity was
      significant; twelve patients had evidence of bilirubin elevations of more than 3
      mg/dl (six in each arm), and two had asymptomatic arterial biliary-tree fistulae:
      one in the HAI+SYC arm and one in the HAI arm. Grade 3 elevation in alkaline
      phosphatase and aminotransferase levels occurred in 26% and 24%, respectively. In
      conclusion, the combination of HAI+SYC is active and safe showing a clinical
      advantage with respect to simple HAI, increasing overall survival, response rate
      and time to progression.

PMID- 17203751
TI  - A multicentric phase II clinical trial on intra-arterial hepatic radiotherapy
      with 90yttrium SIR-spheres in unresectable, colorectal liver metastases
      refractory to i.v. chemotherapy: preliminary results on toxicity and response
      rates.
AB  - BACKGROUND: In patients locally progressing after two lines of chemotherapy, some
      locoregional approaches showed encouraging results in terms of local control of
      disease. The aim of our study was to evaluate toxicity, clinical response and
      quality of life in 48 patients with unresectable colorectal liver metastases
      submitted to selective internal radiotherapy (SIRT). MATERIALS AND METHODS: Up to
      now 35 patients with unresectable colorectal liver metastases, refractory to two
      lines of chemotherapy, underwent intra-arterial infusion of resin microspheres
      with yttrium-90 (SIR-spheres). Pre-treatment evaluation included a CT scan, blood
      tests, a PET scan and arteriography of celiac trunk, hepatic and superior
      mesenteric artery; extrahepatic uptakes and pulmonary shunts more than 10% were
      excluded by a Scinti-scan. The gastroduodenal artery was embolized before the SIR
      spheres injection. Other exclusion criteria were liver dysfunction and anatomical
      vascular anomalies. The clinical response was evaluated by CT-scan following the
      RECIST criteria. Median follow-up was 4 months. RESULTS: Median number of
      metastases was 4 (range, 1-15), 38% of cases presenting hepatic involvement <
      25%. The median SIRT dose delivered was 1.7 GBq. Median pulmonary shunt was 6%.
      No operative mortality occurred; early toxicity (within 48 hours) was 20.6%,
      shown as fever, acute pain and leucocytosis. The late toxicity was 24.1% with
      chronic pain, jaundice and nausea being the most frequent. All the toxic events
      were graded 2 or 3 according to the WHO scale. Preliminary results were available
      in terms of clinical response after 6 weeks: 12.5% had a partial response, 75% a
      stable disease, while progression of disease, was observed in 12.5% of the
      patients. CONCLUSION: SIRT is a safe treatment in terms of acute and late
      toxicity. Intra-arterial microspheres could represent a good therapeutic option
      for patients with progressing liver metastases only, after two lines of systemic
      chemotherapy.

PMID- 17203752
TI  - Thoracic stop-flow perfusion in the treatment of refractory malignant pleural
      mesothelioma: a phase I-II evaluation/trial.
AB  - Malignant pleural mesothelioma (MPM) is an aggressive treatment-resistant tumor
      with a median survival from diagnosis of 12 months. Although multimodality
      protocols that combine aggressive surgery and adjuvant chemotherapy or
      radiotherapy have shown improved survival in selected cases, the majority of
      patients with MPM are not suitable for radical surgery due to advanced stage and
      comorbid medical illness. For these patients combination chemotherapy with
      Pemetrex and Cisplatin should be considered for first line palliative
      chemotherapy. The therapeutic options available to patients with MPM resistant or
      refractory to systemic chemotherapy are very limited. Thoracic "stop-flow"
      perfusion (TSP) is a semi-invasive loco-regional drug delivery system that,
      limiting the circulation to the thorax during the anticancer agent's infusion,
      claims the advantage of reaching high drug concentration at the tumor site while
      maintaining a low systemic toxicity. The aim of this phase I-II study was to
      evaluate the toxicity profile and efficacy of two different platinum-based
      combined regimens--cisplatin plus mitomycin-C (MMC) and cisplatin plus melphalan
      (L-PAM)--administered using TSP technique in patients with advanced or recurrent
      MPM who had refractory disease after systemic first line chemotherapy. Patients
      with histologically proven unresectable stage II-III MPM entered this trial.
      Between January 1995 and December 2001, 27 patients were enrolled in the study
      and submitted to TSP using the two different chemotherapy cisplatin based
      regimens: 12 patients received cisplatin 100 mg/m2 plus MMC 20 mg/m2 (MMC arm)
      and 15 cisplatin 100 mg/m2 plus L-PAM 50 mg/m2 (L-PAM arm). Objective responses
      were assessed by CT-scan 30 and 60 days after the end of treatment in all 27
      enrolled patients. Two patients (7.4%) achieved a complete response, 2 (7.4%) a
      partial response and 4 (14.8%) a minor response. The remaining 19 patients
      (70.3%) showed a stable disease. No patients developed progression of the disease
      following the first TSP. The overall median time to progression was 8.9 months
      (range 1-41). The median survival time for all patients from the beginning of
      regional chemotherapy was 16.6 months, with a 1-year survival rate of 62.9%, a 2
      year survival rate of 18.5%, and a 3-year survival rate of 7.4%. Our data show
      that TSP is a relatively effective second-line treatment in patients with
      progressive disease after systemic chemotherapy, with a low rate of major
      complications and treatment-related toxicity.

PMID- 17203753
TI  - Thalidomide plus monthly high-dose dexamethasone in chemorefractory myeloma.
      Results of a phase II clinical study.
AB  - Thalidomide is a potent anti-myeloma drug which can produce up to a 30-50%
      overall response rate (ORR) in pre-treated, chemorefractory multiple myeloma.
      Most authors agree with using 200 mg/daily with associated high dose
      dexamethasone (40 mg/daily x 4 days, 3 times monthly) considering lower doses
      investigational. We report our experience using thalidomide 100 mg/daily plus
      dexamethasone 40 mg/daily once a month, in 27 pre-treated patients. Thalidomide
      dose excalation and/or association with other drugs were established on the basis
      of the patient's response. Median age was 69 years (range 50-83 years) and 16
      male and 11 female patients were treated. All patients had received more than 1
      treatment line (range 1-5). Thalidomide was increased up to 300 mg/daily in 10
      patients and 1 patient received up to 400 mg/daily. Two patients were not
      evaluable because of early death, 1 did not tolerate thalidomide because of
      pulmonary and neurological side-effects. Sixteen patients responded to this
      treatment, with an ORR of 66%. The combination of low-dose thalidomide plus
      monthly high-dose dexamethasone in chemorefractory myeloma showed interesting
      palliative results. According to our data, increasing thalidomide dosage and/or
      adding further drugs does not generally produce significant improvement.

PMID- 17203754
TI  - A phase II clinical study on relapsed malignant gliomas treated with electro
      hyperthermia.
AB  - The purpose of this study was to evaluate the activity and toxicity of electro
      hyperthermia (ET) on relapsed malignant glioma patients. Twelve patients with
      histologically diagnosed malignant glioma entered the study. Eight patients had
      glioblastoma multiforme, two had anaplastic astrocytoma grade III and two had
      anaplastic oligodendroglioma. All patients were pre-treated with temozolamide
      based chemotherapy and radiotherapy. Hyperthermia with short radiofrequency waves
      of 13.56 MHz was applied using a capacitive coupling technique keeping the skin
      surface at 20 degrees C. The applied power ranged between 40-150 Watts and the
      calculated average equivalent temperature in the tumours was above 40 degrees C
      for more than 90% of the treatment duration. One complete remission and 2 partial
      remission were achieved, with a response rate of 25%. The median duration of
      response was 10 months (range 4-32). The median survival of the entire patient
      population was 9 months, with 25% survival rate at 1 year. ET appears to have
      some effectiveness in adults with relapsed malignant glioma.

PMID- 17203755
TI  - Ten years experience in the treatment of pseudomyxoma peritonei by cytoreduction,
      peritonectomy and semi-closed hyperthermic antiblastic peritoneal perfusion.
AB  - BACKGROUND: In the literature good results have been reported for the treatment
      of Pseudomyxoma peritonei (PMP) by cytoreduction, peritonectomy and hyperthermic
      antiblastic peritoneal perfusion (H.A.P.P.). Forty-eight patients affected by PMP
      have been treated with this technique over the past ten years. PATIENTS AND
      METHODS: Peritoneal perfusion has been performed with the original semiclosed
      tecnique after complete surgical cytoreduction in 188 patients affected by
      peritoneal carcinomatosis. In 48 of the cases the patients were affected from
      PMP. Aggressive surgical cytoreduction was performed with multiple visceral
      resections and peritonectomies. RESULTS: Seventeen patients (38%) presented major
      perioperative complications, and in five cases the reoperation of the patient was
      required. In spite of this high complication rate, there was no perioperative
      mortality. The results of the Kaplan-Meier 5- and 10-year survival analysis, were
      94% and 82%, respectively, with a disease-free survival of 80% at 5 years and 70%
      at 10 years. Thirty-nine patients (81.2%) had no evidence of disease at follow-up
      (range 1-120 months). DISCUSSION: Up to date, the most effective treatment for
      PMP has been aggressive cytoreduction plus H.A.P.P.

PMID- 17203756
TI  - A search for multidrug resistance modulators: the effects of retinoids in human
      colon carcinoma cells.
AB  - The development of multidrug resistance (MDR) is one of the major causes of
      failure in cancer therapy. The use of cell lines with acquired resistance to
      anticancer agents represents a very good tool for investigation into the
      possibility of reversal of MDR. In this study the ability of all-trans-retinoic
      acid (RA) and its derivative 6-OH-11-O-hydroxyphenanthrene (IIF; pat. WIPO W000
      /117143) as antitumor agents was investigated in the human colon carcinoma cell
      line LoVo and in the counterpart resistant derivative LoVo/MDR cell line. Cell
      proliferation was measured by MTT assay, apoptosis was evaluated using DNA
      fragmentation and Annexin V detection assay. Retinoids suppressed cell
      proliferation in a time- and dose-dependent manner. Interestingly, IIF was
      significantly more effective than RA, particularly on LoVo/MDR cells. RA and IIF
      induced apoptosis in both cell lines, with IIF effect significantly higher than
      that of RA. Furthermore, on the basis that MDR phenotype is often caused by drug
      efflux due to overexpression of the membrane P-glycoprotein (P-gp), it was
      demonstrated that RA and IIF reduced P-gp synthesis in LoVo/MDR cells. Our
      results suggest that IIF could be a powerful tool in the development of colon
      carcinoma treatments, even when tumor cells present an MDR phenotype.

PMID- 17203757
TI  - Liposomal doxorubicin with and without TNFalpha in the perfusional treatment of
      advanced soft tissue limb sarcoma: preliminary results.
AB  - BACKGROUND: A combination of doxorubicin and tumor necrosis factor alpha
      (TNFalpha) has been proven to be very effective in the perfusional treatment of
      advanced soft tissue limb sarcoma both in terms of tumor necrosis and limb
      conservative surgery rate. Unfortunately, in some patients a grade IV limb
      reaction has been recorded. The key solution might be the use of liposomal
      doxorubicin (Caelyx) because the carrier seems to release the drug preferentially
      in the tumor rather than in the healthy tissue. PATIENTS AND METHODS: Twenty
      patients were treated with Caelyx: 14 with Caelyx alone and 6 in combination with
      a low TNFalpha dose (1 mg). In the first series of 14 patients a dose escalation
      study was carried out starting from a dose of 10 mg/L of limb volume. Six
      patients were treated with Caelyx (16 mg) and TNFalpha (1 mg). RESULTS: The
      maximum tolerated dose (MTD) was 16 mg/L as in two patients treated with 18 mg/L
      a grade IV limb reaction was observed. Tumor response was satisfactory and
      conservative surgery was carried out in 13 patients. In 6 patients treated with
      Caelyx and TNFalpha, only a grade I limb reaction was recorded, thus, confirming
      that TNFalpha did not increase toxicity, at least at a dose of 1 mg. The Caelyx
      TNFalpha combination did increase treatment efficacy. Tumor necrosis > or = 70%
      was observed in 4 out of 6 patients, one with 100% necrosis (pathological
      complete response). All the patients underwent conservative surgery. CONCLUSION:
      The Caelyx-TNFalpha combination was proven to increase the efficacy of Caelyx
      alone, with a very low toxicity. These preliminary results have to be tested in a
      larger patient population.

PMID- 17203758
TI  - Hyperthermic isolation limb perfusion with TNFalpha in the treatment of in
      transit melanoma metastasis.
AB  - BACKGROUND: Hyperthermic isolation limb perfusion (HILP) with tumor necrosis
      factor alpha (TNFalpha) and IFNgamma was pioneered by Lienard and Lejeune in
      1988. The TNFalpha was empirically employed at a dosage of 3-4 mg, that is ten
      times the systemic maximum tolerated dose (MTD). After eighteen years from its
      first clinical application, more than 300 patients have been treated. The aim of
      this study is to clarify two major arguments: the TNFalpha dose and eligibility
      criteria for patient selection. PATIENTS AND METHODS: A phase I-II study has
      previously been conducted in 20 patients with in-transit melanoma metastases
      using a combination of melphalan and TNFalpha at dosages ranging from 0.5 to 3.3
      mg. Twenty patients were treated and a complete pathological response of 70% was
      recorded, with no correlation between tumor response and TNFalpha. The dose of 1
      mg of TNFalpha provided the best results regarding efficacy and toxicity. On the
      basis of this results a large phase II SITILO study was undertaken. Patients with
      stage IIIA - IIIAB (presence of in transit metastases and/or regional node
      involvement) were considered eligible; a total of 113 patients were enrolled in
      the study. The disease was bulky (> 10 nodules or fewer nodules with a diameter >
      or = 3 cm) in 42.5% of the patients and unresectable in 33%. Forty patients were
      treated with a TNFalpha dosage > 1 mg and 73 with 1 mg. All the patients were
      submitted to HILP via axillary and iliac vessels for tumor of upper and lower
      limb, respectively. TNFalpha was injected in the extracorporal circuit at the pre
      established dose, followed after 30 minutes by melphalan (13 and 10 mg/L of limb
      volume for upper and lower limbs, respectively). RESULTS: A grade 1 and 2 limb
      toxicity was found in 52.9% and 30.1% of the patients, respectively, 5.5% of
      patients exhibited a grade 3 and 4, whereas grade 5 limb toxicity was not found.
      The complete and partial responses were 63% and 24.5%, respectively, with an
      objective response of 87.5%. We tried to correlate the typed tumor response (CR
      or not CR) and the TNFalpha dosage < or = 1 mg or > 1 mg, but no statistically
      significant difference was found between the two groups. The bulky disease was
      the only prognostic factor able to influence the tumor response. CONCLUSION: Only
      patients with bulky melanoma disease can benefit from HILP with TNFalpha at a low
      dose of 1 mg.

PMID- 17203759
TI  - Hepatic arterial chemotherapy with oxaliplatin, folinic acid and 5-fluorouracil
      in pre-treated patients with liver metastases from colorectal cancer.
AB  - BACKGROUND: Hepatic arterial chemotherapy (HAC) is an effective treatment of
      liver metastases from colorectal cancer (CRC). Phase I and II studies have
      already shown the feasibility and efficacy of intra-arterial oxaliplatin (OXA).
      PATIENTS AND METHODS: Twenty-one pre-treated patients with liver metastases who
      received HAC with OXA/folinic acid (FA)/5-fluorouracil (5-FU) at our Division
      between March 2000 and November 2003, were clinically examined. Most patients
      were heavily pre-treated with two or more systemic chemotherapeutic regimes. All
      patients received a percutaneously implanted catheter into the hepatic artery
      through femoral or transaxillary access. Treatment was administered every 14
      days: OXA 100 mg/m2 as a 12-hour infusion on day 1; FA 100 mg/m2 as a 2-hour
      infusion on days 2 and 3; 5-FU 2600 mg/m2 as a continuous infusion on days 2 and
      3. RESULTS: Grade 3-4 toxicities were: asthenia (2 out of 21), transaminase
      elevation (2 out of 21) and pain (2 out of 21), nausea and vomiting (1 out of
      21), neutropenia (1 out of 21), thrombocytopenia (1 out of 21) and neurotoxicity
      (1 out of 21). Main dose limiting toxicity was right upper quadrant pain.
      Response rates were: 5% complete response, 19% partial response, 28% stable
      disease and 48% progressive disease. Two patients became operable and underwent
      complete resection of liver disease. The median overall survival was 36.1 months.
      Two-year and 3-year survival rates were 62% and 52%, respectively. CONCLUSION:
      This regimen is feasible with low toxicity and with an encouraging overall tumor
      growth control (52%) in a subset of heavily pre-treated patients. Intra-arterial
      OXA/FA/5-FU should be considered for the treatment of patients pre-treated with
      systemic chemotherapies with liver metastases from CRC.

PMID- 17203760
TI  - 120 peritoneal carcinomatoses from colorectal cancer treated with peritonectomy
      and intra-abdominal chemohyperthermia: a S.I.T.I.L.O. multicentric study.
AB  - A multicentric study has been carried out on 120 patients affected by peritoneal
      carcinomatosis from colorectal cancer. Patients have been treated by
      cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC)
      with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were
      treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5
      fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal
      perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0
      cytoreduction was achieved in 85.2% of the patients. Major morbidity and
      mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The
      three-year survival was 25.8%. The difference in survival evaluating complete
      cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than
      2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients
      that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In
      our experience the peritoneal cancer index (PCI) has been demonstrated to be a
      weak prognostic factor reaching a statistical significance only after the
      exclusion of patients with resected hepatic metastases. The patients treated with
      oxaliplatin were alive and free-of-disease after a 16-month median follow-up.

PMID- 17203762
TI  - Unresectable hilar cholangiocarcinoma: multimodality approach with percutaneous
      treatment associated with radiotherapy and chemotherapy.
AB  - Klatskin-type cholangiocarcinoma is a rare tumor, bearing a very poor prognosis:
      at diagnosis, most patients can only undergo palliation. Evaluation of outcome,
      mean survival and quality of life was performed in patients with unresectable
      hilar cholangiocarcinoma treated with multimodality approach in comparison with
      surgical palliation, biliary stenting or brachytherapy alone. Twenty-six patients
      with hilar cholangiocarcinoma were studied: 16 patients were enrolled in the
      multimodality protocol (bilateral biliary drainage; Iridium-192 brachytherapy;
      plastic endoprosthesis or metallic stent positioning and external radiotherapy
      plus systemic chemotherapy), 5 patients underwent surgical palliation and 5
      percutaneous decompression alone. Nine patients completed the protocol and 7 were
      treated with brachytherapy followed by biliary stenting alone. The multimodality
      approach obtained mean survival (10 months) similar to that for surgery and
      higher than that of the brachytherapy and metallic stenting groups (6 and 2.75
      months, respectively). The average hospital stay (15 days) was lower than that of
      the surgical group (20 days). A multimodality approach is a suitable alternative
      to palliative surgery of unresectable hilar cholangiocarcinoma.

PMID- 17203761
TI  - Intra-arterial infusion of 5-fluorouracil, leucovorin, epirubicin and carboplatin
      (FLEC regimen) in unresectable pancreatic cancer: results of a ten-year
      experience.
AB  - The final results of a new regimen given intra-arterially for unresectable
      pancreatic cancer (UPC) are presented. PATIENTS AND METHODS: From January 1994 to
      January 2006, 5-fluorouracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60
      mg/m2 and carboplatin 300 mg/m2 were administered every 3 weeks into the celiac
      axis (CA) angiografically (FLEC regimen) to 211 patients with UPC. RESULTS: Seven
      hundred and sixty-four cycles were administered. Grade 3-4 hematological toxicity
      was observed in 24%; ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%;
      grade 3 alopecia in 15%. One sudden death, a pre-infarction angina and a
      transitory ischemic attack were observed. No complications related to the
      angiographic procedure took place, but three tunica intima dissections of the
      iliac artery occurred; 7.6% of patients with partial responses and 50.7% with
      stable disease were observed. Two hundred and one patients have died; median
      overall survival was 9.2 months: 10.5 and 6.6 for stage III and IV, respectively.
      CONCLUSION: The FLEC regimen given intra-arterially is well-tolerated and
      effective in patients with UPC.

PMID- 17203763
TI  - Intra-arterial chemotherapy: a safe treatment for elderly patients with locally
      advanced breast cancer.
AB  - The feasibility, toxicity and local response rates of intra-arterial chemotherapy
      with 5-fluorouracil, epirubicin and mitomycin in patients over 75 years with
      locally advanced breast cancer was evaluated. PATIENTS AND METHODS: Ten patients
      were treated by the transfemoral Seldinger technique, with the catheter tip
      placed into the internal mammary artery. In order to evaluate the vessels
      perfusing the tumor, blue dye solution was infused before drug administration.
      The patients received 5-fluorouracil 750 mg/m2, epirubicin 30 mg/m2 and mitomycin
      7 mg/m2 by bolus infusion. RESULTS: All patients were evaluated for toxicity and
      response. Twenty-two cycles were administered. The toxicity was mild and did not
      influence the patients' quality of life; the compliance was excellent. A response
      rate of 80% (8 out of 10) was obtained; the median overall survival was 33.5
      months; no patient had local recurrence. CONCLUSION: Intra-arterial chemotherapy
      is an effective and safe treatment for locally advanced breast cancer in the
      elderly.

PMID- 17203764
TI  - Radiofrequency thermal ablation in the treatment of lung malignancies.
AB  - BACKGROUND: Radiofrequency ablation (RFA) is an advanced, minimally invasive
      technique used to treat several types of neoplasm. Its application in the
      treatment of lung tumors has received great interest. PATIENTS AND METHODS: Fifty
      four patients with 10 unresectable primary lung tumors and 83 lung metastases
      from various solid tumors were treated with percutaneous RFA. RESULTS: The
      procedure was performed under CT scan guidance and general anaesthesia. The rate
      of complete necrosis of the treated neoplasms was 95%, while the most frequent
      complication was pneumothorax, requiring pleural drainage in 12% of sessions. CT
      scan and MRI with gadolinium have shown to be accurate and useful in assessing
      the therapeutic efficacy of lung RFA. CONCLUSION: Lung RFA is a very promising
      technique, minimally invasive and well-tolerated in the majority of patients;
      further investigation is required in order to define the optimal role of lung RFA
      in the multidisciplinary therapy of lung malignancies.

PMID- 17203765
TI  - Stop-flow perfusion with mitomycin-C as locoregional approach in the treatment of
      large-unresectable liver metastases.
AB  - BACKGROUND: New treatments are being investigated in patients with multiple or
      unresectable liver metastases, usually characterized by poor prognosis. Based on
      the predominant arterial blood supply of hepatic neoplasms, liver transarterial
      chemoembolization administers cytotoxic drugs in combination with the ischemic
      effect due to vascular occlusion. Mitomycin-C (MMC) is characterized by a high
      liver extraction rate and is potentiated by a hypoxic environment. PATIENTS AND
      METHODS: This technique is performed by inducing a stop-flow of the hepatic
      artery, obtained by the placement of a balloon-catheter and followed by the
      infusion of MMC; in addition, in order to prevent iatrogenic lesions of the
      vascular wall, caused by the inflation of the balloon-catheter, a vascular stent
      is placed at the beginning of the procedure. RESULTS: Thirty-one patients with
      liver metastases from various solid tumors were treated, while 47 sessions of
      treatment were performed. Toxicity was moderate; three cases of iatrogenic
      obstruction of the hepatic artery were observed, thus precluding further
      treatment. CONCLUSION: The feasibility and the good tolerability of this
      procedure make it an interesting option in the therapeutical strategy for
      patients with advanced metastatic liver disease, as well as in combination with
      systemic chemotherapy, ablative and cytoreductive treatments and/or free-flow
      liver perfusions with anticancer drugs.

PMID- 17203766
TI  - Cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy (HIPEC) in
      the treatment of pseudomyxoma peritonei: ten years experience in a single center.
AB  - BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare and fatal disease for which no
      standard treatment has been established. Encouraging results have been recently
      reported with the combination of cytoreductive surgery (CRS) and hyperthermic
      intra-peritoneal chemotherapy (HIPEC). PATIENTS AND METHODS: Seventy-five
      patients with PMP underwent CRS and closed abdomen HIPEC with mytomicin-C and cis
      platinum over 10 years at a single institution. Potential clinicopathological
      prognostic variables were tested using multivariate analysis. RESULTS: Optimal
      cytoreduction (residual tumor nodules < or = 2.5 mm) was performed in 72 patients
      (96%). Operative mortality was 1%. Five-year overall (OS) and progression-free
      (PFS) survival were 78.3% and 31.1% in the overall series, respectively. Optimal
      CRS, no previous systemic chemotherapy and low histological aggressiveness were
      independent predictors of better OS and PFS using multivariate analysis.
      CONCLUSION: Favourable outcome after CRS and HIPEC can be expected in patients
      affected by PMP variants with low histological aggressiveness, undergoing optimal
      surgical cytoreduction and with no pre-operative systemic chemotherapy.

PMID- 17203767
TI  - Potential advantages of loco-regional intra-arterial chemotherapy.
AB  - Arterial infusion or perfusion are currently used to treat hepatic tumours, head
      and neck malignancy, melanomas and sarcomas of the limbs. An experimental study
      with epirubicin and cis-platinum infused into the hepatic artery was performed.
      Epirubicin was injected via the systemic vein or the hepatic artery in 27 rats.
      Cis-platinum was injected via a systemic route or the hepatic artery in 29 rats.
      Drug concentrations were evaluated in liver and tumour tissues. In the rats the
      tumour tissue drug concentration after hepatic artery infusion was 6- and 4-fold
      higher than with systemic infusion for epirubicin and cis-platinum, respectively.
      Arterial administration appeared to be better than systemic in terms of drug
      concentration within the tumours and systemic toxicity.

PMID- 17203768
TI  - Whole-body irradiation and long-term modification of bone marrow-derived cell
      populations by low- and high-LET radiation.
AB  - BACKGROUND: The major aim of this study was to quantify long-term changes in bone
      marrow-derived cell populations after exposure to radiations of differing
      quality. MATERIALS AND METHODS: Mice were whole-body irradiated to 2 Gy gamma,
      proton, carbon or iron radiation, and euthanized approximately 110 days later for
      immunocyte phenotyping. RESULTS: Splenic lymphocytes and mono/macrophages
      increased after gamma-rays when compared to 0 Gy and one or more of the other
      groups. There were high T cells (carbon vs. 0 Gy), high B cells (gamma-rays vs. 0
      Gy), and low natural killer (NK) cells (proton and carbon vs. 0 Gy). All
      radiations, except gamma-rays, increased CD62L+ memory T cell counts, whereas
      CD62L+ B cells increased only after gamma-rays. CONCLUSION: There were
      significant aberrations in many immune parameters nearly 4 months after exposure
      to various forms of radiation. This suggests radiation exposure can have long
      term health consequences.

PMID- 17203769
TI  - Effect of EGFR antagonists gefitinib (Iressa) and C225 (Cetuximab) on MnSOD
      plasmid liposome transgene radiosensitization of a murine squamous cell carcinoma
      cell line.
AB  - Radiation therapy of tumors of the head and neck region is compromised by dose
      limiting toxicity of normal tissues including the oral cavity and oropharyngeal
      mucosa. MnSOD-Plasmid Liposome (MnSOD-PL) intraoral gene therapy has been
      demonstrated to decrease normal tissue toxicity and also improve survival in mice
      with orthotopic SCC-VII squamous cell tumors on the floor of the mouth.
      Furthermore, intravenous administration of MnSOD-PL in mice with orthotopic
      tumors, or addition of MnSOD-PL to tumor cell lines in vitro produces a
      radiosensitizing effect attributable to differences in antioxidant pool responses
      of tumor cells compared to normal tissues following irradiation. To determine
      whether EGF receptor (EGFR) antagonists Iressa, or Cetuximab provided further
      improvement of radiation killing of squamous cell tumors, MnSOD-PL transfected or
      control SCCVII tumor cells were irradiated in vitro, and then the effect of EGFR
      receptor antagonists was tested. Cells transfected with MnSOD-PL were relatively
      radiosensitive D0 = 1.244 +/- 0.126 Gy compared to control D0 = 3.246 +/- 0.087
      (p < 0.0001). Clonogenic radiation survival curves of SCCVII cells demonstrated
      radiosensitization by Iressa D0 = 2.770 +/- 0.134 Gy (p = 0.0264), but no
      significant radiosensitizing effect of Cetuximab D0 = 3.193 +/- 0.309 (p =
      0.7338). The combination of MnSOD-PL plus Iressa further increased
      radiosensitivity of SCC-VII cells in vitro D0 = 0.785 +/- 0.01064 (p < 0.0001).
      The results suggest some synergy of the effectiveness of the EGFR antagonist
      Iressa on increasing the radiation killing of SCC-VII cells that supplements
      MnSOD-PL tumor radiosensitization.

PMID- 17203770
TI  - Expression of maspin in colorectal cancer.
AB  - BACKGROUND: Maspin, a member of the serpin family of protease inhibitors, is
      known to be a tumor suppressor. Although the relationship between its expression
      and biological significance has been investigated in several types of cancer, the
      clinicopathological significance of maspin expression in colorectal cancer has
      not been fully elucidated. MATERIALS AND METHODS: The expression of maspin in
      colorectal adenocarcinomas from 104 patients (Ti, T2: 20 patients, T3, T4: 84
      patients) was investigated using immunohistochemical methods and the extent of
      tumor budding was evaluated. RESULTS: The expression of maspin was observed in
      66% (69 of 104) of colorectal adenocarcinomas and was significantly correlated
      with the depth of invasion (p < 0.0001), higher Dukes' classification (p <
      0.0001) and high-grade tumor budding (>9 foci in a field) (p = 0.0001); however,
      no significant correlation was noted concerning lymph node metastases, vascular
      invasion and tumor differentiation. The intensity of immunostaining was most
      strongly observed at the invasion front, especially at the site of tumor budding.
      CONCLUSION: These results suggest that the expression of maspin may correlate
      with the aggressiveness of colorectal adenocarcinomas.

PMID- 17203771
TI  - Age-related differences in repair of dermal wounds and myocardial infarcts
      attenuate during the later stages of healing.
AB  - BACKGROUND: It is unclear whether delays in wound repair due to the age of the
      host persist into the later stages of healing. Late stage healing of dermal
      wounds and myocardial infarcts in rodents was examined to determine if aged
      animals "catch up" to their younger counterparts. MATERIALS AND METHODS:
      Excisional dermal wounds (5 mm) were made by punch biopsy and myocardial
      infarctions were produced by ligation of the left anterior descending coronary
      artery in young and aged mice and rats, respectively. Dermal wounds at day 11 and
      myocardial infarctions at day 14 were analyzed for wound area, angiogenesis,
      deposition of basement membrane proteins, and remodeling of collagen. RESULTS:
      Analyses demonstrated that wound areas, the deposition of basement membrane
      proteins and angiogenic responses were similar in young and aged rodents at late
      stages of wound repair. The dermal wounds of young mice had larger quantities of
      mature, compacted collagen fibers relative to aged mice, but immature collagen
      fibers predominated in myocardial infarcts in both young and aged rats.
      CONCLUSION: These results show that, with the exception of dermal collagen
      remodeling, aged animals catch up to their young counterparts with respect to
      many features of tissue repair. Consequently, therapies that target age-related
      deficiencies in healing will be most effective when administered shortly after
      the initial insult.

PMID- 17203772
TI  - The infectivity of sarcoid clinical material and its bacterial content inoculated
      in CBA mice.
AB  - BACKGROUND: Sarcoidosis is a multisystemic disorder that is currently viewed as
      the consequence of chronic immunological response associating genetic
      susceptibility and specific environmental or transmissible agents. Relevant
      evidence, although conflicting, justifies a concern about the involvement of
      specific pathogens to disease causation. In this study we assessed the
      infectivity of sarcoid clinical material, and of the pathogens found in it, to
      normal CBA mice used as a model of an immuno-competent host. MATERIALS AND
      METHODS: One hundred and eleven mice were inoculated into their footpads with
      fresh, filtered, and autoclaved, sputum and bronchoalveolar lavage homogenates,
      collected from patients with sarcoidosis, and with the mycobacterial and
      propionibacterial pathogens isolated from this material. RESULTS: The total
      number of positive reactors of the animals that received raw clinical material
      and the pathogens it contained was statistically significant compared to those of
      the control groups. However, the number of affected mice per group was in most
      cases less than 50% and inflammation was almost always mild and local.
      CONCLUSION: Based on the evidence provided by inoculation of normal CBA mice,
      some of the material under study, although of mild potency, can be infectious to
      an immuno-competent host.

PMID- 17203773
TI  - Impact of VEGF expression on the physiological characteristics of clonal cell
      lines.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) plays a crucial role in
      tumor angiogenesis and growth in most solid neoplasia. MATERIALS AND METHODS:
      Clonal tumor cell lines expressing varying levels of this pro-angiogenic factor
      were created via recombinant adeno-associated virus infection of a human (HT29)
      and rodent (SCCVII) tumor model. RESULTS: The alteration in VEGF expression
      levels did not significantly impact the in vitro growth rate of the clonal cell
      lines or the expression levels of other known pro-angiogenic factors. However,
      the tumors that arose from these clonal cell lines did display significant
      physiological differences. Upregulation of VEGF expression increased the in vivo
      growth rate and the intratumoral vessel density of the resulting tumors and
      decreased the extent of tumor necrosis. CONCLUSION: Since the tumor vascular
      network can impact the efficacy of anti-cancer therapies, these results suggest
      that VEGF expression may be important to consider in the treatment of cancer.

PMID- 17203774
TI  - Free radical interaction between vitamin E (alpha-, beta-, gamma- and delta
      tocopherol), ascorbate and flavonoids.
AB  - Despite a large number of previous studies, the mechanism of free radical
      interaction between vitamin E (VE) (alpha-, beta-, gamma- and delta-tocopherol)
      and ascorbate or flavonoids as coantioxidants remains unclear. VE, particularly
      alpha-tocopherol, shows less antioxidant activity against peroxyl radicals,
      suggesting that VE possesses functions that are independent of its
      antioxidant/radical-scavenging activity. The synergistic antioxidant effect of VE
      or L-ascorbyl 2,6-dibutyrate (ASDB, an ascorbate derivative) with the flavonoids
      (-)-epicatechin (EC) and (-)-epigallocatechin gallate (EGCG) was investigated
      using the induction period method in the polymerization of methyl methacrylate
      initiated by thermal decomposition of benzoyl peroxide (an oxygen-centered
      radical, PhCOO*) under nearly anaerobic conditions. For delta-tocopherol, a
      synergistic antioxidant effect was observed in the presence of both EC and EGCG,
      whereas antioxidant activity for alpha-, beta- and gamma-tocopherol was decreased
      by addition of EC and EGCG. This suggested that the partial regeneration between
      VE and flavonoids may depend on the chemical structure of VE, i.e., monomethyl,
      dimethyl, or trimethyl tocol. The regeneration of delta-tocopherol, a monomethyl
      tocol, by flavonoids may be due to the lower steric effect of tocol. For ASDB,
      regeneration of vitamin E, which is well-known for a VE/ascorbate mixture, was
      not observed, possibly due to the anaerobic experimental conditions. The radical
      interaction between VE and EC, EGCG or ASDB suggests reactivity of VE with
      biological systems.

PMID- 17203775
TI  - Effects of different durations of estrogen and progesterone treatment on
      development of N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis
      rats.
AB  - BACKGROUND: There have been no precise evaluations of the effects of different
      durations of exposure to estrogen and progesterone pregnancy levels on mammary
      carcinogenesis risk. We examined such effects on the development of N-methyl-N
      nitrosourea (MNU)-induced rat mammary carcinoma. MATERIALS AND METHODS: Female
      Lewis rats were administered a single intraperitoneal injection of 50 mg/kg MNU
      at 28 days of age, and then were either left hormone-untreated (control group),
      or underwent subcutaneous implantation of a 21-day release pellet containing 0.5
      mg 17beta-estradiol and 32.5 mg progesterone (E/P pellet) at 42 days of age. The
      pellet was either replaced every 3 to 4 weeks throughout the experimental period
      (long-term E/P group), or was implanted only once (short-term E/P group).
      Circulating 17beta-estradiol and progesterone levels in the serum, and expression
      of estrogen receptor (ER) a and progesterone receptor (PgR) in the normal mammary
      gland were measured. The rats were sacrificed when they developed a mammary tumor
      with a diameter of > or =1 cm, or when they reached the age of 29 weeks. RESULTS:
      In rats implanted with a single E/P pellet, circulating 17beta-estradiol and
      progesterone levels were significantly elevated 2 weeks after implantation, but
      returned to control levels 8 weeks after implantation; 17beta-estradiol
      transiently reached pregnancy levels. In normal mammary glands of rats sacrificed
      at 29 weeks of age, both long- and short-term E/P treatment decreased the
      percentage of ERalpha- and PgR-positive cells. Rats that received long- or short
      term E/P treatment had a decreased incidence of mammary carcinoma with a diameter
      of > or =1 cm, compared to control rats. However, when histologically detected
      microcarcinomas (diameter <1 cm) were included for comparison, the E/P-treated
      groups exhibited an abrupt increase in the number of microcarcinomas from 22 to
      25 weeks after MNU injection. Although short-term E/P treatment significantly
      suppressed mammary carcinomas of all sizes, long-term E/P treatment had no cancer
      suppressing effect. CONCLUSION: The duration of E/P treatment is an essential
      factor for the suppression of mammary carcinogenesis.

PMID- 17203776
TI  - The PTHrP/PTH.1-R bioregulation system in cardiac hypertrophy: possible
      therapeutic implications.
AB  - Myocardial hypertrophy is associated with specific histological changes, which
      are representative of the cardiomyocytes cellular response to overload.
      Evidently, transcriptional modulation of specific genes is implicated in
      myocardial hypertrophy. Recently, the parathyroid hormone-related protein
      (PTHrP)/PTH-1 receptor (PTH-1.R) bioregulation system was shown to participate in
      specific regulatory processes of the cardiomyocyte function and proliferation,
      which can be related to cardiac hypertrophy and heart failure. We review the
      literature on the pathophysiology of cardiac hypertrophy vis-a-vis the role of
      PTHrP/PTH-1.R system as a good therapeutic target.

PMID- 17203777
TI  - Kinetic radical-scavenging activity of platonin, a cyanine photosensitizing dye.
AB  - Platonin is known to possess antioxidant activity. However, the kinetics of the
      radical-scavenging activities of this compound remain unknown. The aim of this
      study was to investigate the radical-scavenging activities of platonin by the
      induction period method in the polymerization of methyl methacrylate (MMA),
      initiated by thermal decomposition of 2,2'-azobis (isobutyronitrile) (AIBN) (a
      carbon-centered radical, R*), and benzoyl peroxide (BPO) (an oxygen-centered
      radical, PhCOO*), under nearly anaerobic conditions. The number of moles of R* or
      PhCOO* radicals trapped by platonin calculated with respect to 1 mole of
      inhibitor moiety unit (stoichiometric factor, n) was determined, and this showed
      that the n of fully oxidized platonin was 4. The inhibition rate constant
      (k(inh)) of platonin showed a wide range of 0.8 x 10(3) M(-1)s(-1) to 1.6 x 10(4)
      M(-1)s(-1). To clarify the interaction between platonin and thiols, 2-mercapto-1
      methylimidazole (MMI) was used as a representative thiol, because glutathiones
      were unsuitable due to their limited solubility in MMA. MMI in the presence of
      platonin showed neither catalytic activities nor synergistic activities. Platonin
      possesses radical-scavenging activities and acts as an antioxidant. On the basis
      of our experimental results, the radical-scavenging mechanism is discussed.

PMID- 17203778
TI  - Enhancement of cytotoxic activity of sodium fluoride against human periodontal
      ligament fibroblasts by water pressure.
AB  - Whether or not water pressure enhances the cytotoxic activity of sodium fluoride
      (NaF) against human periodontal ligament fibroblast (HPLF) was investigated.
      Loading with water pressure (up to 5 g) alone did not affect the cell
      proliferation, but significantly enhanced the cytotoxic activity of millimolar
      concentrations of NaF. Cytotoxic activity of NaF was reduced by supplementation
      with Ca2+, whereas it was enhanced by removal of Ca2+ from the culture medium.
      However, the enhancement of cytotoxicity of NaF under water pressure was observed
      even in the Ca2+ -free medium. NaF failed to induce apoptosis markers, such as
      the caspase-3, -8 and -9 activation, the intemucleosomal DNA fragmentation, the
      loss of cell surface microvilli and the changes in intracellular concentration of
      polyamines. Transmission electron microscopy demonstrated that the combination of
      NaF and water pressure slightly increased the incidence of the formation of
      autophagosomes engulfing organella, suggesting the induction of non-apoptotic
      cell death in HPLF cells. The present study suggests that the external pressure
      is an additional factor that enhances the cytotoxicity of NaF against HPLF cells.

PMID- 17203779
TI  - Immunomodulation techniques in a pig-to-rat model of xenoislet transplantation to
      prolong graft survival.
AB  - Pancreas allotransplantation can restore full metabolic control in patients with
      type I diabetes, but has several limitations. Pancreatic islet
      xenotransplantation (XiTx) is considered a reliable alternative. The aim of this
      study was to evaluate the effect of gamma-irradiation and a highly selective
      inducible nitric oxide synthase inhibitor (AE-ITU) in a model of pig-to-rat XiTx.
      Thirty-five female rats were made diabetic by intraperitoneal injection of
      streptozocin. Pig pancreatic islets were obtained by enzymatic digestion followed
      by purification on Ficoll gradients. Approximately 4000 purified pig islet
      equivalents were placed under the left kidney capsule of the recipient rats. The
      rats were observed for 15 days and divided into five Groups (G): GI: controls,
      diabetic rats with no treatment; G2: XiTx; G3: XiTx after gamma-irradiation (20
      Gy); G4: XiTx and administration of AE-ITU; G5: XiTx after gamma-irradiation and
      AE-ITU. Graft survival was defined as the maintenance of the glucose levels at
      less than 11 mmol/l and a normal response to i.v. glucose challenge. The graft
      survivals in Groups 2, 3, 4 and 5 were 4.1 +/- 1.8, 7.6 +/- 2.1, 7.6 +/- 2.4, and
      10.9 +/- 2.3 days, respectively. The graft survival of G2 was significantly (p <
      0.05) lower than the other groups, and the graft survival of G5 was significantly
      higher in respect of both G3 and G4 (log-rank test: p = 0.007). In conclusion,
      the combination of AE-ITU (to reduce the early inflammatory damage) and gamma
      irradiation (to reduce the immunogenicity of the islets) may be considered an
      interesting option to prolong the euglycaemic period after XiTx.

PMID- 17203780
TI  - Effect of cell cycle growth arrest on global DNA methylation status in human lung
      epithelial-like (A549) cells.
AB  - BACKGROUND: Decreased global DNA methylation have been previously shown in A549
      cells exposed to prolonged hyperoxia. Because hyperoxia induces growth arrest in
      these cells, whether the status of global DNA methylation changed in response to
      cellular growth arrest was of interest. MATERIALS AND METHODS: A549 cells were
      growth arrested at either the S- or G2/M-phase of the cell cycle by exposure to
      resveratrol (25 microM), or colcemid (0.1 microg/ml) for 24 h. In addition, to
      determine the kinetics of hyperoxia-induced growth arrest, cells were exposed to
      either 1 day of normoxia or 1-5 days of hyperoxia. RESULTS: The data indicate
      hyperoxia-induced G2/M growth arrest after day 2 of exposure onwards. Moreover,
      66.5% of cells were synchronized at the S-phase after exposure to resveratrol and
      97% of them at the G2/M-phase after exposure to colcemid. No changes in global
      DNA methylation status were observed in cells synchronized at either phase of the
      cell cycle. CONCLUSION: These findings indicate that global DNA methylation in
      A549 cells is not determined primarily by hyperoxia-induced cell cycle growth
      arrest.

PMID- 17203781
TI  - Developmental effects of ethinylestradiol on reproductive organs of female mice.
AB  - Reproductive organs in female mice are susceptible to exposure to estrogenic
      substances especially during development. In the present study, C57BL/6J female
      mice were exposed to the synthetic estrogens ethinylestradiol (EE2) or
      diethylstilbestrol (DES), 10-100 or 6.7-67 microg/kg bw, respectively, in utero
      from day 10 to 18 of pregnancy, and their effects were analyzed at 30 and 40 days
      of age. Both EE2 and DES reduced the survival rate of fetuses and newborns in a
      dose-dependent manner. Polyovular follicles (PF) were found in the ovaries of all
      groups at 30 days of age including oil-injected controls. However, the incidence
      of PF was significantly higher in the 50 microg/kg EE2- and 33.3 microg/kg DES
      exposed mice than the control. In vaginal epithelia of the in utero EE2 exposed,
      ovariectomized mice, stratification and cornification were encountered even 10
      days after ovariectomy. Especially, vaginae in the ovariectomized mice given high
      dose of EE2 or DES in utero showed ovary-independent proliferation of the
      epithelium. Thus, it is clear that prenatal exposure to EE2 or DES induces
      reproductive abnormalities, including PF, ovary-independent vaginal epithelial
      stratification and cornification.

PMID- 17203782
TI  - Effect of exercise on oxidative stress in individuals with glucose-6-phosphate
      dehydrogenase deficiency.
AB  - The effect of exercise on oxidative stress in glucose-6-phosphate dehydrogenase
      (G6PD)-deficient individuals was investigated. MATERIALS AND METHODS: Nine G6PD
      deficient males and nine males with normal G6PD activity were selected and
      requested to run at approximately 75% their maximum heart rate for 45 min. Blood
      samples were collected prior to and immediately after exercise. Several
      hematological parameters, reduced glutathione (GSH), oxidized glutathione (GSSG),
      lipid hydroperoxides, thiobarbituric acid reactive substances (TBARS), protein
      carbonyls, catalase and total antioxidant capacity (TAC) were measured in the
      blood before and after each exercise bout. RESULTS: GSH was significantly (more
      than two-fold) higher in the control group compared to the G6PD-deficient group
      at baseline, whereas GSSG, GSH/GSSG and lipid hydroperoxides were not different
      between the two groups. Exercise did not affect the levels of any oxidative
      stress marker. There was no evidence of Heinz body formation neither at rest nor
      after exercise in either group. Exercise of moderate intensity and duration did
      not result in an increase of blood oxidative-stress biomarkers in G6PD-deficient
      males nor in matched controls. It appears that G6PD-deficient individuals may
      exercise without experiencing a rise in oxidative stress at an exercise intensity
      approximately 75% of their maximum heart rate.

PMID- 17203783
TI  - Desmopressin reduces melanoma lung metastasis in transgenic mice overexpressing
      tissue inhibitor of metalloproteinases-1.
AB  - Desmopressin (DDAVP) is a synthetic vasopressin analog capable of inducing an
      increase in the plasma levels of von Willebrand factor and coagulation factor
      VIII. DDAVP has been used during surgery to prevent bleeding in patients with
      coagulation defects. We have previously demonstrated that adjuvant perioperative
      DDAVP therapy inhibits lung and lymph node metastasis in a breast cancer model.
      Here the effect of DDAVP on experimental lung colonization of B16 melanoma cells
      was investigated in a transgenic mice model with high levels of tissue inhibitor
      of metalloproteinases-1 (TIMP-1) in the systemic circulation. Transgenic C57BL/6j
      CBA mice overexpressing human TIMP-1 in the liver under the control of the mouse
      albumin promoter/enhancer were employed. Treatment with DDAVP (2 microg/kg/dose)
      at the time of intravenous injection of B16 cells significantly inhibited the
      formation of lung metastases in TIMP-1 transgenic animals (p = 0.021), while no
      significant effect was obtained in control hybrid mice. The inhibition was not
      due to direct cytotoxic effects of DDAVP on tumor cells and no expression of
      vasopressin receptors was detected in B16 cells. Our data indicate that DDAVP
      therapy may impair successful implantation of circulating melanoma cells and
      suggest that high levels of circulating TIMP-1 display a cooperative role in the
      antitumor activity of the compound.

PMID- 17203784
TI  - Intima-media thickness measurement of the carotid artery in patients with primary
      hyperparathyroidism. A prospective case-control study and long-term follow-up.
AB  - BACKGROUND: The intima-media thickness (IMT) measurement of the common carotid
      artery is recognized as a reliable marker of systemic atherosclerosis and may be
      useful in predicting the likelihood of cardiovascular events, since it is related
      to the extent and severity of coronary artery disease. The aims of this study
      were to analyze whether correlations exist between the IMT of the common carotid
      artery and the main clinical and biochemical parameters in patients with primary
      hyperparathyroidism (PHPT), and to evaluate the possible improvement of the IMT
      values following parathyroidectomy at long-term follow-up. PATIENTS AND METHODS:
      Twenty-seven patients (5 men, 22 women; median age 59 years, range 36-82 years)
      with biochemically confirmed PHPT (Group A, cases), and 27 gender- and age
      matched healthy volunteers (Group B, controls) were prospectively enrolled in the
      study. All patients underwent ultrasound examination and the IMT of each carotid
      artery were recorded, averaging all values. The measurements were repeated 18-22
      months (median 20) later in all patients. RESULTS: A significant (p < 0.05)
      correlation between age and both systolic BP and IMT, and between IMT and fasting
      glycaemia was found in each Group. There was an inverse relationship between IMT
      and serum parathyroid hormone (R = -0.56, p < 0.01), but no correlation (p=NS)
      was found between IMT and serum calcium (R = -0.14) or serum phosphate (R =
      0.07). At follow-up a slight (10.4%) improvement in the mean IMT was observed
      among Group A patients (0.86 +/- 0.18 vs. 0.77 +/- 0.24; p = 0.12), but the
      difference was not significant. CONCLUSION: At long term follow-up, the IMT
      values did not improve significantly and no correlation was found between serum
      calcium and IMT. These results suggest that hypercalcemia does not represent a
      reliable risk of carotid atherosclerosis in patients with PHPT.

PMID- 17203785
TI  - Comparison of lipid and fatty acid metabolism between minimal change nephrotic
      syndrome and membranous nephropathy.
AB  - Polyunsaturated fatty acids have been reported to be associated with
      atherosclerotic and inflammatory diseases, as they are the major components of
      cytoplasmic membranes and the precursor fatty acids for prostaglandins and
      leukotrienes. Nephrotic syndrome is associated with serum lipid disorders, such
      as hypercholesterolemia due to the increased production of lipoproteins by the
      liver. However, there are few reports regarding the fatty acid metabolism in
      patients with nephrotic syndrome. In the present study, serum lipid
      concentrations and plasma fatty acid composition were measured in patients with
      minimal change nephritic syndrome (MCNS) and membranous nephropathy (MN). Seven
      patients with MCNS (MCNS group), 11 patients with MN (MN group) and 8 healthy
      subjects (control group) were enrolled in the study. All patients were diagnosed
      by percutaneous renal biopsy. Fasting blood samples were obtained and the serum
      lipid profile was measured enzymatically. The fatty acid composition of plasma
      was analyzed by gas-chromatography after transmethylation. There were no
      significant differences in serum urea nitrogen and creatinine levels among the
      three groups. Patients with MN were older than those with MCNS. In the serum
      lipid profile, hypercholesterolemia was observed both in the MCNS and MN groups.
      Regarding the plasma fatty acid composition, alpha-linolenic acid levels in the
      MCNS group were significantly higher than those in the control group (1.06 +/-
      0.08 wt% vs. 0.77 +/- 0.16 wt%, p = 0.008) and docosahexaenoic acid levels in the
      MN group were significantly higher than those in the control group (5.51 +/- 1.17
      wt% vs. 3.96 +/- 1.07 wt%, p = 0.005). These results suggest that nephrotic
      syndrome might not only disrupt lipid metabolism but also fatty acid metabolism.

PMID- 17203786
TI  - Association of cognitive impairment with plasma levels of folate, vitamin B12 and
      homocysteine in the elderly.
AB  - BACKGROUND: Alterations in folate, vitamin B12 and homocysteine plasma levels
      have been associated with aging, neuronal development and cognitive impairment.
      The aim of this study was to investigate the relationship between plasma folate,
      vitamin B12 and homocysteine and cognitive function in the elderly. PATIENTS AND
      METHODS: Elderly individuals over 60 years of age living in the community, were
      screened with the Mini-Mental State Examination. The study population was divided
      into two groups: (a) 37 subjects with dementia; and (b) 33 healthy controls.
      Blood samples were analyzed with the use of ELISA, and the results were
      statistically evaluated at p < 0.05 level of significance. RESULTS: Group a had
      significantly lower levels of folate and vitamin B12 than group b. Homocysteine
      was significantly higher in demented individuals than in controls (p < 0.01).
      CONCLUSION: Lower levels of plasma folate and/or vitamin B12 and higher levels of
      plasma homocysteine are associated with cognitive impairment in elderly
      individuals.

PMID- 17203787
TI  - Tissue polypeptide specific antigen and soluble Fas during normal pregnancy and
      early life.
AB  - BACKGROUND: Intrauterine fetal development is characterized by increased rates of
      proliferation and apoptosis, while both these processes may be attenuated post
      natally. AIM: Tissue polypeptide specific antigen and sFas serum concentrations
      were determined during pregnancy and post-natally, in order to evaluate their
      alterations during these crucial periods. MATERIALS AND METHODS: Forty-seven
      healthy pregnant women, their full-term newborns and 35 healthy adults (controls)
      were included in the study. Markers were measured: (a) in maternal serum (MS),
      during the 1st, 2nd, 3rd trimester and at the 1st stage of labor; (b) in the
      umbilical cord (UC), during the 2nd stage of labor; (c) in neonatal serum in the
      1st (IN) and 5th (5N) day after birth; and (d) in controls. RESULTS: The serum
      TPS concentrations in MS increased significantly with gestational age, being
      higher in the 3rd trimester and labor, than those in controls (p < 0.001). TPS
      values were significantly lower in the UC, compared to those in MS (p < 0.001),
      while they were markedly elevated in IN, compared to MS and UC (p < 0.001), and
      subsequently decreased in 5N (p < 0.001), remaining higher, than those in the
      controls (p < 0.001). Serum sFas concentrations in the MS depended significantly
      on gestational age (p < 0.001), being significantly lower in the first trimester,
      than those in the second (p < 0.003), the third (p < 0.03), in labor and controls
      (p < 0.005). sFas concentrations in the UC were significantly lower than in MS
      and controls (p < 0.001), while they increased significantly in 5N samples (p <
      0.01). CONCLUSION: Our results demonstrate: (a) a higher apoptosis rate in the
      first trimester of pregnancy, possibly affecting maternal immuno-tolerance,
      followed by a down-regulation during the post-natal period; (b) a progressively
      increased proliferation from the first trimester to parturition, reflecting the
      fetal and placental growth and development, that seems to be thereafter
      moderated.

PMID- 17203788
TI  - A giant sarcoma of the parotid gland: a case report and review of the literature.
AB  - CASE REPORT: Primary low-grade fibromyxoid sarcoma (LGFMS) is an extremely rare
      tumour of the salivary glands and arises from undifferentiated pluripotential
      mesenchymal cells. We report a case of a huge (17 x ll x 10 cm) primary LGFMS of
      the parotid gland of a 57-year-old woman. Clinically, a 12x8 cm firm, non-tender,
      left parotid mass was observed, facial nerve function was not impaired and no
      enlarged lymph nodules were palpated on the neck. A contrast axial CT scan showed
      intense enhancement of the enlarged left parotid gland. The fine needle
      aspiration biopsy (FNAB) was compatible with sarcomatous tissue. The tumour was
      removed en bloc and the facial nerve was sacrificed; surgical margins were free
      from disease. Microscopically, the tumour consisted of fibrous and myxoid tissue
      with varying grades of cellularity and gradual transitions between the two. Post
      operative radiotherapy was carried out on the left neck region and parotid tumour
      bed. Thirty-six months after surgery the patient presents good general conditions
      without any evidence of local or regional disease. CONCLUSION: The largest
      primary LGFMS of the parotid gland described in the literature is reported and a
      review of the literature on such neoplasms is also provided.

PMID- 17203789
TI  - "Tumor target organs and rate of survival in long-living transgenic mice and
      their parental wild-type counterparts exposed to the carcinogen
      dimethylbenz(alpha)anthracene", by Kossoy George, Herzl Ben-Hur, Ruth Miskin and
      Isthak Zusman. In vivo 20: 543-548, 2006.

PMID- 17203790
TI  - Update on systolic hypertension in the elderly.

PMID- 17203791
TI  - Review of clinical characteristics and management of patients with ST segment
      elevation myocardial infarction at atertiary care center.
AB  - BACKGROUND: Information from recent multiple trials on the pathophysiology and
      outcome of ST-segment elevation myocardial infarction (STEMI) has changed its
      clinical perspective and strategic management, leading to a revision of the 1999
      ACC/AHA practice guidelines for that condition. OBJECTIVE: Analyze the clinical
      characteristics, management strategies, the timing of therapeutic interventions
      and outcome of patients with STEMI referred to the Cardiovascular Center of
      Puerto Rico (CVCPR). METHODS: Retrospective review of medical records of all
      patients admitted to the CVCPR with a diagnosis of STEMI from January 1, 2003 to
      December 31, 2003. RESULTS: A total of 184 medical records were reviewed. Seventy
      six percent of patients were men, mean age was 62.1 +/- 11.8 years. A high
      prevalence of coronary risk factors was present: systemic hypertension (64%),
      diabetes mellitus (40%), dyslipidemia (35%), smoking (33%) and previous CAD
      (32%). Less than 1/4 of referral forms contained data indicative of whether
      patients had received antiplatelet therapy, beta-blockers, ACE inhibitors or
      statins. Fifty percent of patients arrived to the CVCPR more than 48 hours after
      diagnosis. Only forty-two patients (23%) arrived within 12 hours. Thrombolytic
      therapy had been used in 27% of them. 179 (97%) patients underwent coronary
      angiography, 69.2% of which had multivessel disease. 114 (62%) patients underwent
      percutaneous coronary interventions (PCI) with stenting. Patients submitted to
      PCI and stenting of the culprit lesion had a better outcome and survival than the
      ones not exposed to those procedures (p = 0.02). Approximately two-third of
      patients received secondary prevention medications upon discharge. CONCLUSIONS:
      Relevant findings of this review were that in spite of high prevalence of CAD
      major risk factors, the use of medications of proven benefit for prevention and
      treatment of CAD at referral centers was less than that recommended by current
      guidelines, a significant delay in the transfer of patients to the tertiary care
      facility (in most cases that period exceeded more than 48 hours after diagnosis)
      and a reduced utilization of thrombolytic therapy. Intensification of the
      education of physicians throughout the island regarding these matters is to be
      encouraged. Additional measures should include, development of written protocols
      at referral centers to assure a more expedite clinical assessment of patients, an
      enhancement of their capability for utilizing fibrinolytic agents in suitable
      candidates and the timely transfer to PCI-capable facilities of patients that may
      still benefit from catheter reperfusion.

PMID- 17203792
TI  - Coronary artery abnormalities in Puerto Rico.
AB  - A retrospective study was done to determine the frequency of coronary artery
      anomalies in terms of their origin, course, and structure. The clinical history,
      catheterization data and surgical reports of patients undergoing coronary
      angiography at the Cardiovascular Center of Puerto Rico and the Caribbean, from
      1999 to 2004, were analyzed. Thirty-eight patients were identified with a
      coronary artery anomaly in this population. These anomalies were classified
      according to their clinical consequences and the need for surgical intervention.

PMID- 17203793
TI  - Evidence based secondary prevention of coronary artery disease in the elderly-
      2006.
AB  - Eighty percent of coronary deaths occur in people above 65 years of age. Fifty
      percent of deaths in persons above 85 years of age is due to coronary artery
      disease. The overall aging of the population and the improvement in survival of
      patients with coronary artery disease has been creating a growing large
      population of elderly adults who are elegible for secondary prevention. Multiple
      clinical trials and research trials have revealed evidence based information
      confirming the usefulness and effectiveness of secondary prevention of coronary
      artery disease in the elderly patient. The secondary prevention beneficial
      results have been obtained by addressing and controlling the predisposing items
      recognized a coronary risk factors. Secondary preventive measures, including
      lifestyle modifications and pharmacotherapy, modifying risk factors in elderly
      patients, have been shown to reduce morbidity and mortality from coronary artery
      disease. Evidence based data on prevention in elderly patients with coronary
      artery disease concerning smoking cessation, treatment of hypertension, control
      of hyperlipidemia, improved dietary patterns, physical activity, moderation in
      alcohol intake, management of diabetes, weight management, use of antiplatelet
      agents, beta blockers and renin-angiotensin-andosterone blockers is summarized.
      Emphasis has been given to AHA/ACC consensus statements on the prevention of
      coronary artery disease.

PMID- 17203794
TI  - Aortic valvular heart disease in adults.
AB  - Valvular Heart Disease (VHD) is an important cardiovascular problem in the adult
      population. The knowledge of the physiology involved, prompt recognition and
      diagnosis are of paramount importance for the primary care physician who is in
      the front line of patient care. This article is the second of a series of two
      that deals with valvular problems in the adults in concise and practical form
      (11). Each topic will be presented using the following format: description,
      etiology, pathophysiology, natural history, essential of diagnosis and
      management. In this second and final article we will discuss aortic valve
      disorders.

PMID- 17203795
TI  - Cardiovascular disease in HIV infection.
AB  - Cardiovascular disease has been well documented in patients with Human
      Immunodeficiency Virus infection, especially after the introduction of highly
      active antiretroviral therapy. At present, HIV infection is one of the leading
      causes of acquired cardiovascular disease including heart failure. Some of the
      changes observed in these patients include left ventricular systolic dysfunction,
      dilated cardiomyopathy, congestive heart failure, myocarditis, lipodystrophy,
      dyslipidemia, insulin resistance, accelerated atherosclerosis including
      myocardial infarction, prothrombotic state, pericardial effusion, pulmonary
      hypertension, autonomic dysfunction, and malignancy. This article summarizes the
      main findings in the principal HIV-associated cardiovascular manifestations in
      order to stimulate its early recognition so helping in early intervention and
      therapy.

PMID- 17203796
TI  - Diagnosis and management of pericardial effusions.
AB  - Pericardial effusions are a relatively common phenomenon, largely in part due to
      its many possible etiologies. Although a considerable amount of cases are
      idiopathic, careful history and physical examination will reveal the etiology in
      a vast majority of patients. The most effective tools, echocardiography and right
      heart catheterization, should be aimed not only at the diagnosis of the
      pericardial effusion, but also to the assessment of the severity of the
      pericardial effusion, since this will determine that individual patient's
      management. A small, asymptomatic pleural effusion of known etiology can be
      treated conservatively, mostly by treating the underlying cause and with careful
      observation for signs or symptoms of deterioration. Large effusions can be
      treated with closed pericardiocentesis after routine evaluation for possible
      etiologies. For patients presenting actual or impending tamponade, the definitive
      treatment is either closed or open pericardiocentesis, depending on fluid
      accumulation characteristics, and it should not be delayed for the administration
      of medical treatment (inotropes, intravenous fluids). Routine evaluation of
      pericardial fluid is warranted in those cases in which a clear etiology was not
      established prior to pericardiocentesis.

PMID- 17203797
TI  - Heart diseases during pregnancy.
AB  - Improvements in health care services in recent decades have permitted more
      frequent identification of pregnant women with congenital and acquired heart
      disease. Normal pregnancy and the peripartum period are associated with
      considerable cardiocirculatory changes, which are usually well tolerated by the
      mother. However, the increased cardiac demands imposed by those changes may at
      times unmask cardiac disease in presumably normal women or increase morbidity and
      mortality in women with established heart disease. A recognition and
      understanding of these changes is essential for providing optimal care to
      obstetrical patients with cardiac disorders. This article offers a brief review
      of those cardiocirculatory changes during pregnancy and of the main features of
      various congenital and valvular heart disorders frequently referred for advice to
      our cardiology practice, along with recommendations for their management and
      follow up.

PMID- 17203798
TI  - Peripartum cardiomyopathy.
AB  - Peripartum cardiomyopathy (PPCM) is a condition that affects women during the
      reproductive years in the late pregnancy period and/or early postpartum period.
      Although it is associated with several risk factors and various hypotheses exist
      of its etiology the cause of this disorder is still unknown. Standard therapy for
      PPCM is the same as for heart failure. Studies examining new therapeutic
      approaches are adding to the armamentarium available to physicians treating
      patients with PPCM. Despite all the current knowledge the mortality rates
      associated with PPCM remain relatively high. This article is a review of the
      current knowledge of etiology, diagnosis, treatment and prognosis of PPCM and
      attempts to present areas of need of further research.

PMID- 17203799
TI  - Coexistent congenital aortic defects, aneurysm of sinus of valsalva, atrial
      septal defect and infective endocarditis: a case report.
AB  - Coarctation of the Aorta is frequently associated with bicuspid aortic valve.
      This is a risk factor for infective endocarditis. Aneurysm of a sinus of Valsalva
      is a rare defect with a prevalence of 0.09%. They are associated in 10% of cases
      with a bicuspid aortic valve and less frequently with coarctation of the aorta
      and atrial septal defect. It is extremely rare the association of coarctation of
      the aorta with an atrial septal defect. This is one of the first cases reported
      in Puerto Rico of an adult patient with coarctation of the aorta in association
      with a bicuspid aortic valve, a ruptured aneurysm of a sinus of Valsalva and an
      atrial septal defect. The patient is a 22 year old male with coarctation of the
      aorta diagnosed since childhood who was admitted at the Cardiovascular Center of
      Puerto Rico with signs of heart failure due to infective endocarditis secondary
      to a teeth infection. Upon evaluation with transthoracic and transesophageal
      echos, he was found to have a coarctation at the aortic isthmus, aortic root
      dilatation, bicuspid aortic valve with vegetation, severe aortic and tricuspid
      regurgitation, aneurysm of the non coronary sinus of Valsalva with perforation to
      the right atrium, biatrial enlargement and a dilated right ventricle. Successful
      antibiotic treatment of endocarditis was achieved followed by surgical
      replacement of the aortic valve and ascending aorta with closure of the non
      coronary sinus of Valsalva was done. An secundum atrial septal defect was found
      and was also closed. Surgical correction of the coarctation of the aorta was
      postponed for a future time. The patient had a successful postsurgical recovery
      and was discharged home with anticoagulation treatment.

PMID- 17203800
TI  - Primary stenting in a young adult with aortic coarctation.
AB  - A young male adult with significant aortic coarctation was initially referred to
      our clinics due to uncontrolled blood pressures. On evaluation the diagnosis of
      aortic coarctation was evident and confirmed with Magnetic Resonance Angiography
      (MRA). After discussing treatment options with the patient and his parents they
      opted for the least invasive procedure possible. Primary stenting of a simple
      discrete aortic coarctation was performed successfully. The following is a report
      on the methods used and immediate results.

PMID- 17203801
TI  - Uneventful pregnancy and delivery in a patient with idiopathic pulmonary
      hypertension: a case report.
AB  - Idiopathic pulmonary hypertension is a rare disease characterized by sustained
      elevation of the pulmonary artery pressure and pulmonary vascular resistance,
      normal pulmonary artery wedge pressure, in the absence of a known cause. Prior
      reports suggest a very high maternal mortality in patients with idiopathic
      pulmonary hypertension undergoing pregnancy, and for that the recommendation has
      been avoidance of pregnancy (or termination if the patient is already pregnant).
      On the other hand, there have been multiple reports of patients with idiopathic
      pulmonary hypertension sustaining pregnancy and labor without major
      complications. This case report illustrates the course of pregnancy and labor in
      a patient diagnosed with idiopathic pulmonary hypertension. At age 24, the
      patient started with symptoms of shortness of breath and chest pain, and upon
      evaluation she was found with moderately severe idiopathic pulmonary
      hypertension. One year and 8 months later the patient becomes pregnant, and
      begins follow up with gynecology and cardiology. During this time the patient was
      asymptomatic, and did not have any clinical evidence of pulmonary hypertension.
      The risks of pregnancy were discussed with the patient, and she decided to
      continue pregnancy. She had an uneventful pregnancy, complicated only by preterm
      labor at 34 weeks and 5 days of gestation. She had spontaneous labor and
      delivered vaginally a healthy baby boy, weighting 4 pounds and 12 ounces. No
      invasive monitoring was used. The mother and the baby were discharged home 48
      hours postpartum. Seven months later the patient returned for evaluation,
      presenting evidence of severe pulmonary hypertension. She has been followed up
      ever since by a cardiologist and currently is stable but symptomatic. This report
      adds to the amount of evidence that suggests that pregnancy and labor in a
      patient with idiopathic pulmonary hypertension may have a better outcome than
      previously reported. The decision of undertaking and/or continuing pregnancy in a
      patient with idiopathic pulmonary hypertension relies ultimately on the patient's
      choice, but should be done on an individual basis after careful evaluation of the
      risks. Finally, the need of close follow up with a multidisciplinary team is
      mandatory in the patient with idiopathic pulmonary hypertension that wishes to
      undergo pregnancy.

PMID- 17203802
TI  - [Staphylococcal infections as an important problem in intensive therapy--own
      clinical observations].
AB  - The microbiological monitoring in the Intensive Care Units, in the last few
      years, revealed a significant increase of infections caused by Gram+ bacteria.
      Authors of multi-center studies focus upon the problems related to the treatment
      of the infections caused by the methicilline-resistant staphylococci (MRS) as
      well as to its spreading. The Staphylococcal infections were 26.6 % of all
      bacterial infections in the Intensive Care Unit of the Department of
      Anesthesiology and Intensive Care of the Medical Academy in Bialystok, during one
      year observation. MRS rods counted 21.4% among all pathogens isolated from the
      specimens collected from the patients, undergoing the treatment in the ICU, and
      were responsible for 83.6% of all Staphylococcal infections. The analysis
      revealed the significant percentage MRS rods resistant to commonly used empirical
      antibiotic therapy. Our experience shows that vancomycin or linezolid should be
      used, as an empirical antibiotic therapy, in suspected MRS-caused severe
      infections along with the simultaneous monitoring of changes in G+ bacteria drug
      resistance and strict infection-control regime.

PMID- 17203803
TI  - [The influence of Candida albicans on the course of ulcerative colitis].
AB  - The influence of microbiological factor is taken into consideration in the
      pathogenesis of ulcerative colitis (UC). The aim of studies was to: 1.evaluate
      the presence of significant fungal colonization, over 10(5) CFU/ml in patients
      with UC and the control group (irritable colon syndrome, IBS); 2. estimate the
      influence of antifungal treatment in the activity of UC. MATERIAL AND METHODS: We
      evaluated 72 patients aged from 18-72 years, 60 patients with UC, 12 with IBS.
      Clinical investigation: initially and after 4 weeks interview and colonoscopy
      with colon biopsies for histology and mycology were taken. Activity of UC was
      evaluated according to: clinical, endoscopic and histological IACH criteria. 13
      patients with significant fungal colonization were given antifungal treatment.
      Biopsies for histology were stained with hematoxylin-epsin (H-E). Qualitative and
      quantitative mycolo-gical evaluation was performed according to Muller method.
      RESULTS: 1. Significant fungal colonization was more frequent in patients with UC
      history over 5 years, in comparison with shorter disease history and IBS, in
      33.3%, 13.8% and 1.3% respectively. 2. Candida albicans was most often isolated
      in 91.7% of cases. 3. Initial analysis of the activity index of UC in patients
      with significant and non-significant fungal colonization did not revealed
      differences between these groups, 13.84 and 14.0 respectively. 3. After 4 weeks
      stronger decrease of the UC activity index was observed in patients with
      significant fungal colonization treated with antifungal treatment, in comparison
      with patients not given antifungal therapy: 8.0 and 10.41 respectively, p<0.01.
      Differences were significant according to clinical 2.23 (C) -3.33 (D), p<0.05 and
      endoscopic cryteria: 3.46 (C) -4.84 (D), p<0.01. CONCLUSIONS: 1. Significant
      fungal colonization of colon may influence the activation of UC. 2. Longer
      disease history may be the risk factor of significant fungal colonization in
      colon. 3. Antifungal treatment in patients with significant colonization caused
      clinical improvement of UC.

PMID- 17203804
TI  - Prevalence and basic determinants of hepatitis C antibodies in medical students
      in Katowice, Poland.
AB  - BACKGROUND: Potential exposure of medical students to infectious material and the
      lack of specific prevention measures could contribute to an increased risk of HCV
      infection in this group. OBJECTIVE: To find out if the occurrence of HCV
      antibodies is more frequent in medical students than in non-medical students and
      to determine risk factors for HCV antibodies in students. METHODS: A cross
      sectional study performed in 2003-2004 included 566 medical students (Medical
      University, Katowice) and 517 students of non-medical faculties (University,
      Katowice). HCV antibodies were determined using the 3rd generation EIA test, in
      doubtful cases a Western-blot INNO-LIA-HCV confirmation test was applied. Risk
      factors were identified based on questionnaire derived data. Between-group
      difference in the prevalence of positive anti-HCV tests was evaluated by means of
      ch2 test and candidates for risk factors were evaluated according to logistic
      odds ratios. RESULTS: Prevalence of HCV antibodies was statistically
      insignificantly lower in medical students (1.4%) than that in non-medical
      students (1.9%). In the group of 1068 subjects with no history of ever-diagnosed
      viral hepatitis the respective figures were 1.4% and 1.7%. In this group the
      presence of the positive anti-HCV tests was associated with dermal cosmetic
      interventions in the past (logOR=4.85), percutaneous medical interventions
      (excluding surgery) (logOR=3.18) and individual history of blood transfusion
      (logOR=1.71). However, the results were not statistically significant.
      CONCLUSIONS: Medical students at the Medical University in Katowice, Poland are
      not at increased risk of HCV infection. The findings suggest an important role of
      cosmetic and percutaneous medical interventions, and blood transfusion as risk
      factors for HCV infection.

PMID- 17203805
TI  - [Anastomotic leakage following anterior resection for rectal carcinoma].
AB  - With the improvement of surgical techniques anterior resection with the
      preservation of the anal sphincter has become the preferred operative option for
      rectal cancer. This procedure is associated with the problem of anastomotic
      leakage (AL). The reported rate of symptomatic AL is 1-29% but 20-77% of AL do
      not produce any typical clinical symptoms. Risk factors of AL involve: older
      patient's age, male gender, low site of anastomosis, pre-operative radiation,
      emergency admissions, major intraoperative bleeding, concomitant diseases and
      perioperative blood transfusion. Apart from clinical examination and peripheral
      blood tests, contrast enema, endoscopy, transrectal sonography and CT imaging can
      be helpful to diagnose AL. Minor AL may be usually managed conservatively, intra
      abdominal abscess can in most cases can be treated by radiologically guided
      drainage. Major AL and cases with peritonitis require relaparotomy. The risk of
      permanent stoma after AL is 25-30%. AL-related mortality is reported from 0 to
      40%. Effectiveness of surgical techniques potentially protecting the anastomosis,
      as defunctioning stoma, suction-irrigation drainage, omentoplasty, no-suction
      pelvic drainage and transanal decompressive tubbing is still not proven and
      remains disputable. Impact of AL on functional results is not unequivocally
      cleared. AL may significantly increase local recurrence rate and should be
      considered as an independent prognostic factor influencing poor long-term
      survival.

PMID- 17203806
TI  - [Allergic rhinitis and food allergy].
AB  - Atopic diseases are a serious problem of current medicine due to epidemiological
      range. It also concerns allergic rhinitis and food allergy. Associations between
      allergic rhinitis and food allergy is still a developing subject and literature
      concerning its relationship is not to numerous. A short literature review of
      studies and reviews concerning the above subject was performed. Differences of
      epidemiological data concerning the association between allergic rhinitis and
      food allergy were presented and pathophysiology of this correlation is not
      precisely known. Nevertheless conclusion can be made that in cases of allergic
      rhinitis with diagnostic difficulties, food allergens can be taken into
      consideration as possible etiologic factors. Problem of correlation between
      allergic rhinitis and food allergy is an open subject and there is a need for
      further studies.

PMID- 17203807
TI  - [Mastocytosis in childhood].
AB  - Mastocytosis is a rare multi-symptomatic disorder with overproduction and
      accumulation of mast cells in different tissues. Mast cells accumulate most often
      in skin, rarely in bone marrow, lymphnodes, liver and spleen. Symptoms of the
      disease may be due either to releasing of mediators that are present in mast
      cells or to affection of organs. Although mastocytosis is regarded as a rare
      disease in the population, among patients of dermatologists it is much more
      common. It concerns 5,4 caser per 1000 of cured children. The disease has no
      original treatment. There is a chance that thanks to to popularisation of
      knowledge of this disease will be more frequently diagnosed and known better.

PMID- 17203808
TI  - [Mast cells, their adenosine receptors and reactive oxygen species in chronic
      inflammatory pathologies of childhood].
AB  - Mast cells were described by Erhlich at the end of XIX-th century. Their role was
      deeply investigated in asthma and allergy. The massive degranulation of mast
      cells in allergy can lead to anaphylactic shock. Recently, mast cells have been
      recognized again as a very interesting topic for investigation, due to their
      possible role in chronic inflammation. Moreover, through adenosine receptors,
      mast cells can be activated or inactivated. That is why these cells are regarded
      as a potential target of new drugs. It has been reported, that mast cells
      generate intracellular reactive oxygen species (ROS) in response to stimulation
      with divergent physiologically relevant stimulants. The intensification of ROS
      production may be measured by the level of carbonyl groups, as a marker of
      protein peroxidation. However, the role of mast cells in other than asthma
      diseases with chronic inflammation needs further investigation. It was found out
      that the information about mast cell distribution in colonic mucosa may serve as
      help in differentiation between inflammatory bowel disease and collagenous
      colitis. Moreover, its accumulation in focal active gastritis was confirmed in
      patients with Crohn's disease. An important role in regulation of inflammatory
      process seems to be reserved for adenosine receptors present on mastocytes. The
      activation of mast cells through the adenosine receptor is connected with 11-8
      release, which stimulate the migration of leukocytes and oxidation reactions. The
      detection of mast cells in tissues should not be limited only to the simple
      histologic examination. It should be completed by the detection of products of
      degranulation, e.g. tryptase. This is the way to find out their actual function
      and state of activation.

PMID- 17203809
TI  - [Acne rosacea--diagnostic challenge].
AB  - Acne rosacea is a common skin disorder which affects adults, usually women.
      Erythema, papules, pustules and telangiectases, the main clinical manifestations
      of the disease are located on the face. Currently opinions dealing with
      pathogenesis and clinical forms of rosacea are presented. As the clinical picture
      might be confusing, similar to other illnesses, differential diagnosis with other
      dermatoses like acne vulgaris, erysipelas, seborrhoeic and contact eczema as well
      as systemic diseases like lupus erythematosus, dermatomyositis, scleroderma,
      sarcoidosis and leukemia were discussed.

PMID- 17203810
TI  - [C-reactive protein in cardiovascular diseases].
AB  - The half of all hart attacks and strokes occurred among persons without elevated
      LDL- cholesterol concentration. This statment indicates a necessity for
      consideration of additional factors allowed for identification of patients with
      high risk of cardiovascular diseases, other than high cholesterol level. The
      precise determination of inflammation in the atherogenesis process paid attention
      to biological inflammatory markers as indicators of development and course of
      atheromatosis related diseases. C-reactive protein ranked as an acute phase
      protein, produced by the liver as an answer to cytokine stimulation is an
      acknowledged inflammatory marker. The measurement of CRP concentration is
      traditionally used to establish diagnosis and course as a monitor of inflammatory
      and neoplastic diseases. The last few years brought a lot of data that suggested
      usefulness of CRP concentration measurements in cardiovascular diseases. Putting
      into diagnostics the measurement of CRP as a high sensitivity CRP method allowed
      to precisely determining the connection between atherogenesis process development
      and its complications. The aim of this paper is presentation of current knowledge
      concerning connection between CRP and cardiovascular diseases.

PMID- 17203811
TI  - [Diagnostic and therapeutic aspects of dialysis-related amyloidosis].
AB  - The definitive diagnosis of dialysis-related amyloidosis based on histologic
      findings suffers from invasive surgical procedure and punctual information.
      Imaging techniques: ultrasonography, X-ray, computed tomography or magnetic
      resonance are relatively nonspecific and not sensitive enough. Scintigraphy using
      radio-labelled beta-2-microglobulin currently represents the most specific method
      to noninvasively diagnosis dialysis-related amyloidosis. Available therapeutic
      methods include the removal of BMG and palliation of symptoms. Hemodialysis high
      flux and hemodiafiltration based on convection are more effective in elimination
      of BMG than standard hemodialysis with diffusive transport as a dominant
      mechanism. Use of the adsorption columns Lixelle reduces plasma BMG concentration
      and leads to clinical improvement of DRA. Medical therapy consists of the use of
      low dose corticosteroids and non-steroidal anti-inflammatory drugs. Surgical
      therapy is often necessary in the late stages of DRA. Renal transplantation is
      still the optimal method of DRA treatment.

PMID- 17203812
TI  - [Hepatorenal syndrome].
AB  - Liver and kidney are essential organs for maintaining metabolic balance because
      of their detoxificational, excretory and regulatory functions. Liver
      insufficiency, especially alcohol-induced hepatocirrhosis with ascites may cause
      functional, potentially reversible kidney failure known as hepatorenal syndrome
      (HRS). Hepato-renal syndrome is the reason for 8-30% cases of acute kidney
      failure in cirrhotic patients. It is also an independent risk factor of mortality
      in this group of patients. There are two types of HRS with different dynamics of
      clinical course and different prognosis for long term survival of patients. The
      only efficient treatment for HRS is transplantation of liver or it's right lobe
      from a living donor. Transplantation removes unbeneficial effects of liver
      failure and also in most cases restores proper kidney function. The other methods
      of treatment concentrate to improve and retain kidney function as long as
      possible and simultaneously to reduce mortality in patients awaiting for liver
      transplantation. Some of them are: administration of intravenous albumin,
      diuretics and arterial vasoconstrictors or correction of portal hypertension with
      a trans-jugular intrahepatic portacaval shunt (TIPS). In patients qualified to
      liver transplantation renal replacement therapy should also be undertaken. The
      newest supporting extracorporeal technique for liver insufficiency with/or
      without HRS is albumin dialysis with MARS of Prometheus devices.

PMID- 17203813
TI  - [Eosinophil cationic protein as a marker of eosinophil activity].
AB  - Eosinophil cationic protein (ECP) is one of the markers released by eosinophils.
      It suggests that ECP can be a good laboratory measurement for late allergic phase
      assessment. ECP can be measured in serum, BAL, sputum or nasal lavage. There are
      many studies that document the use of ECP in such diseases like: bronchial
      asthma, pollinosis or food allergy, but their results are not uniform.

PMID- 17203814
TI  - [Anticonvulsants treatment of psychiatric disorder in elderly patients].
AB  - Agents introduced for the treatment of epilepsy have also been usedsimultaneously
      for psychiatric indications. The therapeutic effects of anticonvulsants are
      recognized in many psychiatric disorders. Growing literature suggests that
      anticonvulsant medication have efficacy in treating acute mania, bipolar
      disorder, psychotic disorders, behavioral disturbances especially agitation and
      impulsive aggression and anxiety, alcohol withdrawal and dependence. However,
      study of anticonvulsants among elderly patients has been limited. Further
      research in the field of psychogeriatry is needed to clarify the efficacy and
      tolerance of anticonvulsants.

PMID- 17203815
TI  - [Pathogenesis and histopathology of pseudoexfoliative lesions. The eyeball
      disease or ocular manifestation of a generalized process?].
AB  - Pseudoexfoliation syndrome, known since nearly hundred years, is considered at
      present as generalized disorder of the extracellular substance metabolism,
      although its etiology and pathogenesis remain unclear. Its morphological
      manifestation includes accumulation of fibrillar material deposits in ocular
      tissues which may be a ground for various ocular pathologies, in particular the
      open-angle glaucoma for which the syndrome is the most common identifiable cause.
      In patients with ocular deposits aggregates of similar material were recently
      identified in the skin as well as in some internal organs (e.g. heart, lung,
      liver, kidney). However, their clinical significance is not clear--some evidences
      suggest their association with transient ischemic attacks or aortic aneurysm
      formation. Numerous recently presented epidemiological data and improvements in
      basic sciences brought a new insight into the syndrome, up to now regarded as a
      purely ophthalmologic matter. Histopathological features as well as actual
      knowledge on the pathogenesis of the pseudoexfoliation syndrome is described.

PMID- 17203816
TI  - [Medical criteria of delaying or stopping imprisonment].
AB  - Estimating the subject's ability to undergo imprisonment and determining whether
      there are any reasons for delaying or stopping imprisonment, has become a serious
      problem. Currently the Polish system lacks clear and homogenous opinionating
      criteria, and the available sources provide only general guidelines. This results
      in a great deal of discrepancy between opinions and evaluations made in similar
      cases. This work attempts to define and illustrate the criteria of the Executive
      Penal Code that are used in evaluating whether imprisonment is to be delayed or
      stopped. The authors have also provided examples of illnesses that would
      illustrate those definitions/criteria and came up with a suggested procedure of
      decision-making to be applied to such cases.

PMID- 17203817
TI  - [Ethical and legal issues concerning renal replacement therapy withdrawal or
      withholding].
AB  - Rapid and dynamic increase of the number of patients that need different forms of
      renal replacement therapy can be noticed in the developed countries. This
      increase is associated with increased number of patients with 'diseases of modern
      civilization', such as diabetes and hypertension, which lead to kidney
      complications (e.g. diabetic and hypertensive nephropathy). Improved long-term
      care (especially diabetic and cardiologic) allows these patients to survive
      longer and to reach the stage of end-stage renal disease. This leads to
      increasing age and morbidity of patients treated with dialysis. In many cases,
      due to extremely advanced level of co-morbidity patients on dialysis are exposed
      to extreme level of suffering and unacceptably low quality of life. Persistent
      continuing of renal replacement therapy under such circumstances (with no hope
      for recovery or improvement) raises also some economical issues, especially in
      the context of permanent crisis and shortage of resources in health systems of
      most countries in the world. In this review the current practice concerning
      withdrawal or withholding of renal replacement therapy as well as some legal and
      ethical issues of this practice are discussed.

PMID- 17203818
TI  - ST-deviation, C-reactive protein and CPK-MB as mortality predictors in acute
      myocardial infarction.
AB  - Prognosis varies widely in patients with acute coronary syndromes because of the
      heterogeneous nature of this condition. Successful outcome depends upon early
      risk stratification and an early decision regarding the approach of management of
      these patients. We studied 120 patients admitted with acute myocardial
      infarction, who were subsequently divided into two groups based on their final
      outcome (improvement or expiry). C-reactive protein and CPK-MB were
      quantitatively estimated at the time of hospital admission. Also, the number of
      ECG leads showing ST deviation and its sum was calculated and correlated with the
      biochemical markers. Differences in these variables were analysed between the two
      groups of patients. Significant differences were found in the mean levels of CRP,
      CPK-MB, the number of ECG leads with ST deviation and its sum between the two
      groups. Also, significant correlation was found between the levels of biochemical
      markers and the sum of ST deviation at admission in all patients of acute
      myocardial infarction.

PMID- 17203819
TI  - Angle closure glaucoma: a cause for bilateral visual threat.
AB  - Glaucoma is one of the leading causes of blindness worldwide. Primary angle
      closure glaucoma (PACG) is a leading cause ofblindness in East Asian people and
      known to cause bilateral blindness more frequently than other glaucoma. A
      retrospective study was thus undertaken to see the visual profile among these
      cases attending glaucoma unit. Total of 387 cases of angle closure glaucoma were
      seen in 3 years period. Out of these, 278 (71.8%) were females and 109 were males
      (28.2%). Among total cases, 61.5% had chronic angle closure glaucoma (CACG) and
      38.5% had acute angle closure glaucoma (AACG) in one or both eyes. Bilateral
      angle closure attack was encountered simultaneously in 16 of the total acute
      angle closure cases accounting for 10.7%. Vision evaluation at the time of
      diagnosis among chronic angle closure glaucoma revealed blindness in 97 patients
      accounting for 20.4%. In acute glaucoma cases, after breaking the acute attack,
      the prevalence of blindness was found to be 8.9% out of total cases. Bilateral
      blindness was seen in 17.6% of total cases presented with either acute attack or
      chronic glaucoma. Mean intraocular pressure (IOP) was 32 mmHg (SD = 9.456) and 44
      mmHg (8.67) in CACG and AACG respectively. Cataract was associated in 15.1% of
      CACG and 12.8% of AACG. Cataract related blindness was presumed to be present in
      only 4.1% cases of CACG and 14.3% of AACG cases who were blind. (p = < 0.001)
      Angle closure glaucoma is the frequent cause of bilateral blindness.

PMID- 17203820
TI  - Evaluation of anti-inflammatory activity of Calotropis gigantea (AKANDA) in
      various biological system.
AB  - To evaluate the effect of Calotropis G in various experimental animal models. The
      anti-inflammatory activity was evaluated using carrageenin-induced kaolin 
      induced rat paw oedema for acute and cotton-pellet granuloma, adjuvant-induced
      arthritis model for chronic inflammation. Antipyretic activity was carried out
      using yeast induced pyresis method. Phenylquinone--induced writhing method in
      mice was used for analgesic activity. Test compounds exhibited variable anti
      inflammatory activity and peak activity of the test compounds were reached at 2
      h. Alkaloid fraction possesses comparatively high initial anti-inflammatory
      activity. The residual anti-inflammatory activity of alkaloid fraction of
      Calotropis G suggest either a greater protein binding nature of the compound
      there by providing a slow released pool of active drug molecule in the system or
      non available of possible bioactive metabolites to retain the activity profile
      relation.

PMID- 17203821
TI  - Clinical evaluation of corneal astigmatism in non diabetic and diabetic patients.
AB  - This study aimed to measurement of corneal astigmatism in non diabetic and
      diabetic patient with Keratometry. This perspective study was conducted at Nepal
      Medical College Teaching Hospital from March to June 2004 to find out clinical
      evaluation of corneal astigmatism in non diabetic and diabetic patients. A total
      224 patients were include. Corneal astigmatism readings with the Takagi KM-1
      Sutcliff type Keratometry was obtained by single examiners on 130 non diabetic
      patients (where as 112 right eye and 109 left eye) and 94 diabetic patients (both
      eyes) corneas. Corneal dioptric and magnitude of astigmatism were assessed.
      Average corneal diopters were 43.88 and 43.81 in non diabetic and diabetic cases.
      Average corneal astigmatism was 0.30 D and 0.07D in non diabetic and diabetic
      cases. Less astigmatism present on diabetic patient to compare non diabetic
      patients in total and both sex. Chances of diabetes mellitus are more visible in
      non astigmatism patient compare to astigmatism patients in both sexes (Table-1
      and 2). No difference in astigmatic rule i.e. with the rule astigmatism in both
      diabetic and non diabetic patients but less astigmatism present in diabetic one.

PMID- 17203822
TI  - Intestinal parasitic infections among HIV seropositive and high risk group
      subjects for HIV infection in Nepal.
AB  - Present study was carried out to find out the prevalence of intestinal parasites
      in HIV seropositive (HIV+) subjects and high risk group (HRG) for HIV infection
      in Nepal. A total 196 (HIV+: n = 112; Age: 16-52 years and HRG: n = 84; Age: 16
      39 years) individuals were included. Stool specimens were examined by direct
      smear, formal-ether sedimentation, Sheather's sucrose floatation and Kinoyun
      modified Ziehl-Neelsen methods. Overall prevalence of intestinal parasites was
      35.7% (70/196) (26.7% in HIV+ subjects and 47.6% in HRG subjects). Trichuris
      trichiura was the commonest parasite in HIV+ subjects (50.0%), whereas hookworm
      was most common among HRG subjects (56.8%). There was an association of parasitic
      infections with the gastrointestinal tract symptoms in both the study subjects.
      Tibeto-Burmans study subjects had marginally higher prevalence than Indo-Aryans
      study subjects (P > 0.05). Multiparasitic infections were relatively more common
      among HIV+ subjects (7.2%) in comparison to HRG subjects (4.8%). Similarly the
      protozoan infections were relatively higher in HIV+ subjects (4.5%) compared with
      HRG subjects (1.2%). The opportunistic protozoa Cryptosporidium parvum was
      detected only in 5.2% HIV+ subjects.

PMID- 17203823
TI  - Retinoblastoma in Nepal: a clinical profile of 30 cases.
AB  - To determine the clinical profile of retinoblastoma and to provide baseline data
      for further studies on this subject. Prospective evaluation of 30 consecutive
      patients with retinoblastoma admitted at the B. P. Koirala Lions Center for
      Ophthalmic Studies, Kathmandu, Nepal, between October 1998 and July 2000 was
      carried out. Age, sex, laterality and time from onset of symptoms to diagnosis
      (lag time) were noted. Ancillary tests were undertaken to rule out metastasis.
      Male to female ratio was 1.1:1 and the median age of presentation was 3.1 years.
      Of 30 cases, 23 (76.6%) had unilateral involvement. Leukocoria was the presenting
      sign in 13 cases (43.3%) and fungating mass in 10 cases (33.3%). In 11 (36.7%),
      the latency period from onset of symptoms to diagnosis was 6-12 months. In
      bilateral cases, advanced disease was treated surgically and the fellow eye was
      treated with cryotherapy, photocoagulation and chemotherapy. Histopathological
      examination of 21 (70.0%) enucleated/exenterated cases revealed a poorly
      differentiated type of retinoblastoma. This is the first study of retinoblastoma
      from Nepal. Early diagnosis of this disease when it is localized to the eye is
      important to salvage the life of the child. An informational program directed
      toward the public in general, as well as careful screening of any white pupillary
      reflex by the pediatrician and/or primary health worker will encourage and
      support early diagnosis.

PMID- 17203824
TI  - Correlation of gestational age by sonographic measurement of fetal parameters in
      women in eastern Nepal with existing standard normograms.
AB  - This is the prospective study carried out to correlate gestational age by
      sonographic measurements of fetal parameters by normograms of Frank P Hadlock
      with the gestational age by Last Menstrual Period (LMP) (considered our standard)
      in various trimesters of normal pregnant women of eastern Nepal. Seventy normal
      pregnant women with regular menstrual cycles of eastern Nepal were evaluated in
      this study. Gestational age was calculated by Rempen (in case of Mean Sac
      Diameter) and Hadlock (in case of Biparietal Diameter, Head circumference,
      Femoral Length and Abdominal circumference) normograms. Calculations of
      gestational age was also done by LMP at the same time. Correlation of gestational
      age by Rempen and Hadlock with average of different fetal parameters in different
      trimesters was done with gestational age by LMP applying paired t test. On
      applying paired t test between gestational age by Mean Sac Diameter and Crown
      Rump Length in the first trimesters, mean difference was only -3.58 days
      (significance < 0.01). It showed statistically significant difference though
      difference is little. Paired t test application in second trimester showed
      significant difference (-5.06 days) with gestational age by LMP at < 001
      significance level. In 3rd trimesters, paired t test showed significant
      difference with gestational age by LMP with mean of difference -7.86 days.
      Significant difference between average gestational age by Hadlock and gestational
      age by LMP in 2nd and 3rd trimesters of pregnancy indicates that we should
      stantardise our measurements of different fetal parameters for estimation of
      gestational age.

PMID- 17203825
TI  - Stroke: a case series study in Nepal Medical College Teaching Hospital.
AB  - Stroke is a major public health burden worldwide. Prevention programme are
      essential to reduce the incidence of stroke and to prevent the all but inevitable
      stroke epidemic, which will hit our population (developing countries) hard as our
      population age and adopt lifestyle of the more developed countries. In this study
      we have tried to find the clinical characteristics of the stroke patients
      admitted in NMCTH and the commonest risk factors and its magnitude in our
      population. In these retrospective clinical case series study, we included the
      cases which were admitted in NMCTH over the past 2 years (from 1st April 2003 to
      31st march 2005). All these patients were confirmed cases of stroke (CT scan was
      done in all these cases). Clinical profiles of all these patients were studied
      and analyzed using SPSS 11.0 version software. Seventy two patients were
      diagnosed as having cerebrovascular accident. The mean age of the patients having
      stroke in our study was 61 years. The commonest symptom was unable to move one
      side of the body (90.0%), other common symptoms were slurring of speech (33.0%),
      loss of consciousness (29.0%), headache (23.0%) and deviation of mouth (22.0%).
      70 patients (97.0%) had 2 or more than 2 symptoms (i.e. multiple symptoms).
      Smoking (61.0%), hypertension (60.0%) and atrial fibrillation (8.0%) were the
      commonest modifiable risk factors, while increased age (mean 61 years) was the
      commonest nonmodifiable risk factor. Ischemic stroke (68.0%) was common than
      hemorrhagic (32.0%) stroke. In this study we found that smoking and hypertension
      was the commonest risk factor in our study group. Atrial fibrillation (8.0%) and
      diabetes mellitus (8.0%) were among the less common risk factors, whereas
      alcoholism and hypercholesterolemia were negligible in our study population.
      Multiple clinical features are common with unable to move the one side of the
      body being the commonest. The commonest form of stroke detected in our study
      group was ischemic type which is comparable to the study done in the past.
      Despite of these findings a bigger epidemiological study is needed to generalize
      this view over our community.

PMID- 17203826
TI  - Percutaneous transvenous mitral commissurotomy.
AB  - Two hundred patients underwent Percutaneous transvenous mitral commissurotomy
      (PTMC) from January 2003 to July 2004. Seventy four percent of the patients were
      female. Age ranged from 10 years old to 61 years and mean age was 29 years.
      Twenty three percent of the patients were under 21 years of age. Atrial
      fibrillation was present in 32.0% of the cases. Mean mitral valve area increased
      from 0.90cm2 (+/- 0.14) to 1.82cm2 (+/- 0.21) (p = 0.018). Left atrial mean
      pressure decreased from 21 mmHg mean to 7 mmHg. Subjective improvement was
      reported in 98.0% of the patients immediately after the procedure. There was no
      mortality during the hospital stay or within the first month of the procedure.
      Significant mitral regurgitation of grade 3 was noted in 5 patients. Two
      developed severe mitral regurgitation. The complications were negligible. One had
      systemic embolisation during the procedure which recovered over a period of time.
      One developed deep vein thrombosis which recovered after treatment.

PMID- 17203827
TI  - Age related changes in cholesterol level among the patients with subclinical
      hypothyroidism in eastern Nepal.
AB  - This study was undertaken at Biochemistry Department (BPKIHS) from 2001 to 2002.
      The aim of this study was to assess whether subclinical hypothyroidism is
      associated with abnormal cholesterol level in different age groups. Of the cases
      referred to the department, 398 euthyroid controls, 189 hypothyroid cases, 179
      hyperthyroid cases and 181 subclinical hypothyroid cases were enrolled for
      further analyses. Both the sexes showed increased total cholesterol levels in
      hypothyroidism, and were not significantly changed in hyperthyroidism than in
      euthyroid controls. Female subclinical hypothyroid cases of age group 45-59 years
      and both the male and female cases of age group > or = 60 years had significantly
      (p < 0.01) elevated total cholesterol levels (196 +/- 37.36 mg/dl vs.169.37 +/-
      29.12 mg/dl, 211.5 +/- 30.48 mg/dl vs. 151.54 +/- 55.84 mg/dl and 225 +/- 25.05
      mg/dl vs. 181.73 +/- 32.95 mg/dl respectively) as compared to euthyroid controls.
      When data were analyzed at 33 and 45 years of age cut offs, the cases of > or =
      33 years age in both hypothyroid male and female showed significantly (p < 0.01)
      elevated cholesterol levels (222.66 +/- 29.26 mg/dl vs. 156 +/- 37.09 mg/dl and
      231.66 +/- 46.17 mg/dl vs 198.1 +/- 48.72 mg/dl respectively) where as
      subclinical hypothyroid female showed increased total cholesterol level (211 +/-
      31.2 mg/dl vs. 157.95 +/- 45.92 mg/dl) at > or = 45 years age cut off. It is
      concluded that hypothyroidism not the hyperthyroidism is associated with
      increased total cholesterol level in the cases of this region, and we advise
      routine screening for cholesterol level in both the sexes of hypothyroid (for >
      or = 33 years) and female subclinical hypothyroid (for > or = 45 years) cases in
      this area, as they have high risk for higher cholesterol levels and developing
      related disorders.

PMID- 17203828
TI  - Epidemiology and etiopathogenesis of urinary calculi in western Nepal (Pokhara).
AB  - Urinary stone disease is recorded in the literature from the dawn of the history
      and has spared no segment of society irrespective of age, gender, occupation and
      socio-economic status. It is still termed as "Refractory Disease" as complete
      medical management to prevent occurrence or recurrence is not so far available.
      We conducted a preliminary survey from the Manipal Teaching Hospital and carried
      out urinalyses to ascertain risk factors in the local population. This
      preliminary survey indicates the prevalence of stone disease is in moderate zone.
      Hyperoxaluria is an important risk factor in more than one fourth of the stone
      formers; and hypernatriuria is distinctly most common potentiating risk factor.

PMID- 17203829
TI  - Microbial study of hospital environment and carrier pattern study among staff in
      Nepal Medical College Teaching Hospital.
AB  - The present study was done to see the microbial flora in the environment (air and
      surface) of Nepal Medical College Teaching Hospital and the staffs working in the
      hospital. Altogether 160 environmental (air n = 43, surface n = 117) samples were
      collected and studied from different wards. Similarly 150 samples (48 nasal
      swabs, 48 throat swabs and 54 hand samples) from the staffs were collected and
      studied following the standard microbiological protocols. Gram +ve cocci were the
      most predominant ones among the bacterial isolates from the environment followed
      by gram +ve bacilli and gram -ve bacilli. Among fungal isolates, yeast were the
      most common isolates while Aspergillus spp. were the most frequently occurring
      mold. Out of 150 samples collected for the study of carrier pattern, 32 out of 54
      samples collected were found to have Staphylococcus aureus in their hands, 1 had
      Escherichia coli. Other isolates were Bacillus spp., Micrococci and coagulase
      negative staphylococci. Similarly 21 (43.8%) out of 48 nasal samples were found
      to have S. aureus while none of the staffs were found to have beta-hemolytic
      streptococci in their throat. In the study, 1.6% environmental isolates and 5.7%
      carrier isolates of S. aureus were found to be Methicillin resistant.

PMID- 17203830
TI  - Assessment of carotid artery dimensions by ultrasound in non-smoker healthy
      adults of both sexes.
AB  - Assessment of carotid artery lumen diameter and intima-media thickness is
      becoming as a surrogate marker of early evaluation of cardiovascular disease.
      Present study aims to describe the normal carotid dimensions in healthy adults of
      both sexes. A total of 123 healthy volunteers including 65 men and 58 women, aged
      21 to 60 years (mean +/- SD; 35.66 +/- 8.84 years) were studied. Ultrasound study
      of both carotid arteries were performed with a 7.5 MHz linear array transducer.
      Common carotid artery lumen diameter ranged from 4.3 mm to 7.7 mm. Difference was
      not noted between left and right common carotid artery lumen diameter (5.78 +/-
      0.57 mm and 5.86 +/- 0.66 mm), and internal and external carotid artery lumen
      diameter as well. Both left and right common carotid artery, internal and
      external carotid artery lumen diameter tended to be larger (p < 0.05) in men than
      women. Common carotid artery intima-media thickness ranged from 0.4 mm to 0.8 mm.
      Difference was not noted between left and right common carotid intima-media
      thickness when separately analyzed among men, women and the entire population.
      Difference was also not noted in comparison between men and women. CONCLUSION:
      Common carotid artery and internal and external carotid artery lumen diameter
      tends to be larger in men than women among young adults. There is no difference
      between left and right carotid artery lumen diameter. Common carotid artery
      intima-media thickness is similar in comparison between left and right and both
      sexes.

PMID- 17203831
TI  - Hyper-echoic plaque with high attenuation in intravascular ultrasound may predict
      slow flow during percutaneous coronary intervention.
AB  - One patient with acute inferior wall myocardial infarction underwent percutaneous
      coronary intervention following intravenous thrombolysis. Intravascular
      ultrasound (IVUS) before stenting revealed huge plaque burden with high
      attenuation underneath the hyper-echoic eccentric plaque surface. Stent
      deployment resulted in slow flow, which was managed with intra-aortic balloon
      counter-pulsation. His another lession in the mid left anterior descending artery
      showing eccentric hypo-echoic plaque with neither hyper-echoic surface nor high
      attenuation was successfully stented without causing slow flow.

PMID- 17203832
TI  - Angiolymphoid hyperplasia with eosinophilia (alhe): a rare entity for
      otolaryngologist.
AB  - A case of angiolymphoid hyperplasia with eosinophilia (ALHE) is reported. It is a
      rare and new disease for an otolaryngologist. The difference between the Kimura's
      disease and ALHE has been discussed. Though it is rare, ALHE should be kept in
      differential diagnosis for an auricular swelling.

PMID- 17203833
TI  - Epigastric mass in a young girl: trichobezoar. Imaging diagnosis.
AB  - A 16-year old girl presented with a history of abdominal pain, lump in
      epigastrium since one year. The ultrasound examination showed an epigastric mass,
      which was delineated as a filling defect in the stomach on barium studies. Upper
      GI endoscopy showed a large intragastric mass composed of hair. The CT scan
      showed a gastric mass extending to the duodenum. She was managed by surgical
      removal. A large gastric trichobezoar extending upto the jejunum was found. This
      case highlights the characteristic radiological appearance on barium, ultrasound
      and computed tomography of a bezoar within the stomach and a trichobezoar with a
      long tail extending upto the jejunum without intestinal obstruction is unusual.

PMID- 17203834
TI  - First case of cutanous leishmaniasis in Nepalese patient.
AB  - Visceral Leishmaniasis (VL) is a serious disease caused by Leishmania donovani
      (LD) complex and prevalent in the temperate and tropical zones of the earth. VL,
      endemic in the southern plains of the 14 districts in the Terai region of Nepal,
      is considered a major public health problem. Cutanous leishmaniasis (CL) is
      prevalent mainly in the tropics and subtropics, affects nearly 1.5 million people
      worldwide. No reported cases of CL have been identified in Nepal until now. We
      report the first case of CL in a Nepalese patient.

PMID- 17203835
TI  - [Nitric oxide as an inflammation marker at non-specific ulcerous colitis and
      Crohn's disease].

PMID- 17203836
TI  - [Application of the breath hydrogen test in gastroenterology].
AB  - The diagnostic capacities of the breath hydrogen test in gastroenterology are
      discussed in the article. The authors describe the results of their own research-
      determination of the intestinal bacterial contamination in patients with chronic
      biliary pancreatitis with the help of the Micro H2 breath hydrogen analyzer.

PMID- 17203837
TI  - [Manometry as a method of assessment of the esophageal motor function].

PMID- 17203838
TI  - [Impact of hydrochloric acid and HP-invasion on the cavitary pressure in the
      duodenal and gastroesophageal region in patients with ulcer].
AB  - The goal of the study was to examine the cavitary pressure (P) in the duodenal
      and gastroesophageal region under the impact of acidification of the duodenum (D)
      and depending on the hydrochloric acid gastric secretion (HCL) and Helicobacter
      pylori (HP) infection in patients with ulcer. Endoscopic manometrography
      performed in 205 patients (with duodenal ulcer, gastric ulcer and chronic
      gastritis) revealed a considerable (p<0.05) increase in P (mmHg) in the D (9.4 +/
      0.4 vs. 11.8 +/- 1.0) and in the antral region of the stomach (ARS) (9.6 +/- 0.3
      vs. 11.4 +/- 0.6), decreased pylorus tone (33.9 +/- 4.6 vs. 17.5 +/- 6.0) and
      pressure gradients (AP) between the low esophageal sphincter (LES) and D (6.6 +/-
      0.4 vs. 3.9 +/- 1.3) in patients with increased basal acid secretion (BAS (BAS >
      10 mm/hour vs. BAS < 7 mm/per hour). Acid infusion of 0.1N HCL in 39 patients was
      accompanied by the increase of P in the D (from 9.7 +/- 1.1 to 13.1 +/- 1.2), ARS
      (from 8.6 +/- 1.3 to 12.8 +/- 1.4) and tendency to the reduction in the P in the
      pylorus (from 28.2 +/- 2.5 to 20.6 +/- 3.6) as well as feeling of pain in all
      patients with active duodenal ulcers. The presence of HP in 47 out of 87 patients
      as compared to its absence was associated with the increased deltaP in the D-ARS
      (-0.6 +/- 0.43 vs. 2.1 +/- 1.1) and reduced deltaP in the LES-D (8.3 +/- 1.6 vs.
      3.4 +/- 1.5) and deltaP LES-ARS (14.3 +/- 1.3 vs. 9.8 +/- 1.2) as well as more
      marked esophagitis (0.64 +/- 0.09 vs. 0.38 +/- 0.11 conventional units, p <
      0.05). HP and hypersecreation of HCL synergistically or additively increase the
      antroduodenal tonic tension, promote the LES incompetence and further damage of
      the esophageal mucous coat.

PMID- 17203839
TI  - [New capacities of the probiotic therapy in the treatment of the irritated bowels
      syndrome].

PMID- 17203840
TI  - [Experimental study of the impact of a single use of indometacine on the
      morphological structure of the mucous coat of the stomach and small intestine].
AB  - A single application of the indometacine in the dose of 60 mg per kilogram of
      body weight had an ulcerogenic action in 100% of cases. The alterations in the
      inucous coat of the stomach appeared as dystrophic changes in the integument and
      fossa epithelium and disorders in the microcirculation. The increased acidity of
      the gastric juice can be associated with the observed increase in the amount of
      parietal cells. Changes in the mucous coat of the small intestine testified to
      the development of inflammation.

PMID- 17203841
TI  - [People and their symbiotic microflora: general biological aspects of the
      problem].
AB  - This article describes the role of the intestinal microbiocenosis in the
      development of metabolic, immunologic, morphologic disorders of the
      gastrointestinal tract as well as mechanisms of the association of the intestinal
      endoecology and bacterial metabolites with the mental status, intellectual
      characteristics and social functions of people.

PMID- 17203842
TI  - [Functional results of the surgery of esophageal opening hernia].
AB  - The article presents an original method of laparoscopic anti-reflux surgery,
      immediate and long-term results of the treatment of 132 patients with esophageal
      opening hernia. It also describes the analysis of the life quality of patients
      with the gastroesophageal reflux disease before and after the surgery.

PMID- 17203843
TI  - [A rare case of metastases in the diaphragm in a patient with gastric cancer].
AB  - In spite of the general affection of the greater curvature of the stomach, there
      were no dyspeptic manifestations, pains in the upper half of the stomach were not
      related to meals, 'and the stool remained unchanged. The main characteristic of
      the clinical picture was the distribution of the tumor process to the diaphragm,
      which was a reason explaining the complaints about acute pains in the right flank
      enhancing in the course of movements or deep breaths. No data about any
      metastatic affection of the skeleton bones, lungs or pleura were received. This
      case shows the need in the close examination of the diaphragm in the case of the
      pain syndrome in the right hypochondrium in patients with generalized tumor
      diseases.

PMID- 17203844
TI  - [Ulcerous colitis and Crohn's disease in members of one family: case description
      and review of literature].

PMID- 17203845
TI  - [Metabolic structures of the blood serum--markers of acute pancreatitis].
AB  - The goal of the study was to reveal the meaning of metabolic structures of the
      blood serum (BS) in the diagnostics of acute pancreatitis (AP). Along with
      standard methods of examination, cystalloscopical examination of the BS was
      conducted for 46 patients with AP. The BS of 22 healthy people was used as
      control. In this group, the structure of BS had a form of threadlike bipalmate
      crystals. Metabolic structures of BS in patients with AP were characterized by
      signs of enzymatic dysfunctions: hyperamylasemia was presented in the form of
      subparallel lamellae, hypertrypsinaemia - in the form of a dendritic grid,
      hyperlipasaemia--in the form of bubble chambers with branches. Hyperhistaminemia
      was characterized by the presence of optically active feathered spherolithes,
      hyperserotonemia--by plateau dendritic aggregates, and markers of
      hyperelastasaemia were aggregates of rectangular and prismatic crystals.
      Hyperimmunoglobulinaemia M was characterized by skeleton cruciform crystals, and
      hyperimmunoglobulinaemia G--by skeleton crystals branching from the main axis at
      an acute angle. The optically active dendrite-like crystals were revealed at
      hypercreatinemia, and selective structures of BS were found at dysproteinaemia,
      hypersyalaemia, hyperdophaminaemia, hyper-beta-endorphinaemia,
      hyperacetylcholinaemia and hypertryglyceridaemia. The revealed microtypes can be
      used for the visual diagnostics of metabolic disorders at AP and for control over
      the treatment efficacy.

PMID- 17203846
TI  - The cosmetics of dentistry. Who will be left smiling?

PMID- 17203847
TI  - A greater risk.

PMID- 17203850
TI  - Democracy and dentistry. A medical profession within a democracy.

PMID- 17203849
TI  - Dental urban myths. Should we worry?

PMID- 17203851
TI  - Dental management of the gravid patient.
AB  - Gravidity is defined as the development of the young in utero. It initiates
      hormonal, psychological and physiological changes in the female patient,
      providing the dentist with many questions about the management of these patients.
      These physiologic alterations, as well as the embryologic development of the
      fetus, will be discussed along with the treatment alterations that should be
      considered. The changes are often subtle, but can lead to disastrous
      complications if proper precautions are not taken. Conversely, appropriate
      management of routine and dental emergencies can be denied by the practitioner
      because of misconceptions about pregnancy and fetal tolerance. Anesthetic and
      pharmacology of agents used in dentistry in treating the pregnant patient will be
      reviewed.

PMID- 17203852
TI  - Ectodermal dysplasia. A seven-year case report.
AB  - This case report describes the manifestations of ectodermal dysplasia and tracks
      the seven-year management of a male ED patient. It demonstrates the benefits of
      early intervention, describes restorative and orthodontic treatment rendered, and
      a range of future treatment options available when early intervention is
      employed.

PMID- 17203853
TI  - Conventional root canal therapy of C-shaped mandibular second molar. A case
      report.
AB  - The C-shaped root canal system and treatment implications were first described by
      Cooke and Cox in 1979. C-shaped canals are most frequently found in mandibular
      second molars, but they can occur in any mandibular molar, and they have been
      reported in maxillary molars as well. C-shaped mandibular molars are
      characterized by a C-shaped groove that connects one or more root canals. This
      groove can occur anywhere along the root canal system, making it difficult to
      diagnose and treat. A C-shaped root canal system may appear completely normal at
      the level of the pulp chamber but can begin to manifest itself in the middle or
      apical one-third. Furthermore, C-shaped canals are challenging if not impossible
      to predict radiographically. C-shaped canals in mandibular second molars are
      found most frequently in the Chinese population, with reports showing up to a
      31.5% incidence, as compared to an approximate 7% incidence in the general
      population. This case report demonstrates an incidence of a C-shaped canal that
      was unable to be detected radiographically and which contained three separate
      root canals that communicated in the apical one-third of the root canal system.
      Canal orifices were located approximately 2 mm below the level of the CEJ, which
      is in agreement with a recent micro-computed tomography study of C-shaped
      mandibular molars that found 98% of all C-shaped molars studied had orifices
      located 1 mm to 3 mm below the CEJ. The CT study also found that all C-shaped
      canals contained fused roots and confirmed previous findings that the C-shape
      configuration varies greatly throughout the length of the canal.

PMID- 17203854
TI  - Diagnosing bulimia nervosa with parotid swelling. Case report.
AB  - Patients with bulimia nervosa (BN) may show dental erosion, resulting from the
      effect of acid regurgitation. Asymptomatic bilateral parotid swellings may also
      be present. Other signs include serum electrolyte imbalance and Russell's sign.
      The authors describe the case of a 26-year-old woman with BN, whose only clinical
      manifestation of BN was her bilateral parotid swellings. Because patients with BN
      tend to be secretive about their purging, it is important that the clinician
      consider BN as part of a differential diagnosis when faced with such painless
      parotid gland swellings.

PMID- 17203855
TI  - Cavernous hemangioma of the palate. A review of etiology, pathogenesis and
      treatment options.
AB  - Cavernous hemangiomas of the palate are a rare but not infrequent sighting in the
      oral and maxillofacial region. The etiology and pathogenesis of these lesions are
      not definitively understood and are currently being explored. Treatment options
      usually include, but are not limited to, surgical excision of the lesion.
      Alternative management paradigms should be considered when dealing with this type
      of lesion. Precaution should be taken before any surgical intervention.

PMID- 17203856
TI  - The Lumen Technique. Retrieval of broken gold screws in dental implants.
AB  - A technique for removing a broken abutment screw from internally threaded
      endosseous implants and salvaging the endosseous implant is presented. The
      technique involves the use of inexpensive instruments found in dental offices.

PMID- 17203857
TI  - Jacob Hemet. Dentist to royalty and entrepreneur extraordinaire.
AB  - One of the most prominent dentists in late-18th century London was Jacob Hemet,
      member of a long family of dentists. He was appointed royal dentist to Queen
      Charlotte, wife of George the Third, and to George's favorite daughter, Amelia,
      and the Prince of Wales. He advertised widely, both in this country and in
      several European countries, including his native France. However, what makes him
      noteworthy is the fact that he was the very first person to patent a dentifrice
      and the first to use marketing techniques similar to those used by the foremost
      toothpaste manufacturers of today.

PMID- 17203858
TI  - Ketoprofen ion-selective electrode and its application to pharmaceutical
      analysis.
AB  - The composition of a polymeric potential-determining phase for ketoprofen
      selective electrode has been determined and the following basic electrode
      parameters were examined: measurement range, slope characteristic, limit of
      detection, response time, lifetime and selectivity coefficients in relation to
      some organic and inorganic anions. The electrode have been used for ketoprofen
      determination in the range 25.43-25430 microg/mL.

PMID- 17203859
TI  - Synthesis and properties of 4-alkoxy-2-[2-hydroxy-3-(4-o,m,p-halogenoaryl-1 
      piperazinyl)propyl]-6-methyl-1H-pyrrolo-[3,4-c]pyridine-1,3(2H)-diones with
      analgesic and sedative activities.
AB  - Synthesis of N-substituted derivatives of 4-alkoxy-6-methyl-1H-pyrrolo[3,4
      c]pyridine-1,3(2H)-diones (17-26) is described. The chlorides, containing OH
      group, used in the above synthesis can exist in two isomeric forms: chain (12, 14
      16) and cyclic (12a, 14a-16a). All final imides studied exhibited analgesic
      activity in the "writhing syndrome" test which was superior than that of
      acetylsalicylic acid. In the "hot plate" test only two compounds (19, 20) were
      active as antinociceptive agents. Furthermore, all compounds tested significantly
      suppressed the spontaneous locomotor activity of mice.

PMID- 17203860
TI  - Synthesis of new 1-(amino)-3-[(1,5-diphenyl-1H-1,2,4-triazol-3-yl) oxy] propan-2
      ol and 1-[(1,5-diphenyl- 1H- 1,2,4-triazol-3-yl) oxy]-3-(4-arylpiperazin-1-yl)
      propan-2-ol derivatives with an expected beta-adrenolytic activity.
AB  - 3-(Oxiran-2-ylmethoxy)-l ,5-diphenyl-lH-1,2,4-triazole [I] was obtained in the
      reaction of 1,5-di-phenyl-IH-1,2,4-triazol-3-ol with 2-(chloromethyl) oxirane.
      Then I was converted into the corresponding aminoalkanol derivatives of 1,5
      diphenyl-IH-1,2,4-triazol-3-ol, IIa,b -VIIa,b. Molecular structure of I was
      confirmed by an X- ray structure analysis. The receptor affinities for IVa, VIIa
      were determined.

PMID- 17203861
TI  - Synthesis of amino derivatives of 10-(diphenylmethylene)-4
      azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione as potential psychotropic and/or
      anti HIV agents.
AB  - A series of amino derivatives of 10-(diphenylmethylene)-4
      azatricyclo[5.2.1.0(2.6)]dec-8-ene-3,5-dione, analogues of chlorpromazine and
      aminoperazine have been prepared. These compounds are expected to have
      antipsychotic and/or anti HIV activity. Molecular structure of III was confirmed
      by an X-ray structure analysis. The cytotoxicity and anti HIV activity of
      derivatives I-IV were determined.

PMID- 17203862
TI  - Synthesis and serological interactions of H. pylori urease fragment 321-339 n
      terminally immobilized on the cellulose.
AB  - Antigenic epitopes F8 (SIKEDVQF) and UB-33 (UreB fragment with residues 321-339:
      CHHLDKSIKEDVQFADSRI) in H. pylori urease that induces neutralizing antibody
      production were prepared on the cellulose plate from N- to C-terminus using CDMT
      as a coupling reagent. Reaction of both epitopes with sera of patients with
      medically confirmed atherosclerosis was studied. Strong, selective reactions of
      both peptides with some patients sera were observed.

PMID- 17203863
TI  - Synthesis of new derivatives of 2,3-dihydro-7-benzo[b]furanol with potential
      pharmacological activity.
AB  - A series of 13 new ether-linked derivatives of 2,2-dimethyl-2.3-dihydro-7
      benzofuranol have been designed and synthesized. Seven of them were evaluated for
      anti-HIV potency. They showed a relatively high cytotoxicity and a low anti-HIV-
      I activity.

PMID- 17203864
TI  - Anti-inflammatory activity of Achillea and Ruscus topical gel on carrageenan
      induced paw edema in rats.
AB  - The anti-inflammatory activity of Achillea and Ruscus extracts was studied in
      comparison with diclofenac sodium topical gel (diclosal Emulgel), using the
      carrageenan induced paw edema model in Albino rats. Gel formulation was prepared
      containing 6% of each extract in gel base, namely sodium carboxymethylcellulose
      (NaCMC). The kinetics of drug release from the prepared formulation was studied
      separately in each case. Results showed that the release follows the Higuchi
      square root equation. The pharmacological screening revealed that the percent
      reduction of edema for Achillea extract and Ruscus extract were 48.1% and 18.8%,
      respectively, while diclosal Emulgel produced 47% reduction of edema.

PMID- 17203865
TI  - Comparative study of phenolic acids in pseudofruits of some species of roses.
AB  - A free and liberated by acid and alkaline hydrolysis phenolic acids from the hips
      of fourteen species of wildly growing roses were identifed and determined using
      SPE RP HPLC method. Eleven major phenolic acids (gallic, protocatechuic,
      gentisic, p-hydroxybenzoic, vanillic, caffeic, syringic, p-coumaric, ferulic. p
      hydroxyphenylacetic, salicylic) were quantitatively investigated. The amount of
      individual compounds ranged from 0.2 mg/g to 303.2 mg/g of dry material.
      Conjugated forms of phenolic acids were predominated in the fruits and they were
      hydrolyzed mainly to gallic acid (93-303 mg/g in dry plant material). The total
      amount of phenolic acid after hydrolyses was from 186.4 mg/g (R. inodora) to 466
      mg/g (R. rugosa) of dry weight of plant material.

PMID- 17203866
TI  - Determination of ellagic acid in pseudofruits of some species of roses.
AB  - Ellagic acid (EA) is known as a naturally occurring dietary antimutagen and
      anticarcinogen with strong antioxidant and anti-inflammatory activities. An SPE
      RP HPLC method was optimized and applied for identification and determination of
      ellagic acid in hips of fourteen species of roses, wildly growing in Poland. A
      large amount of total EA, ranged from 487.2 to 1065.2 microg/g of dry material
      was found. The results suggest that studied materials are good sources of dietary
      ellagic acid and could be used as a natural antioxidant and functional food.

PMID- 17203867
TI  - Physicochemical and microbiological properties of eye drops containing
      cefuroxime.
AB  - The purpose of the studies was to examine the influence of the additives and
      storage temperature on physicochemical properties and on the antimicrobial
      activity of cefuroxime in the eye drops. The eye drops were 1% sterile aqueous
      solutions of cefuroxime in citrate buffer of pH 6.15-6.20, preserved with 0.002%
      thiomersal or 0.001% phenylmercuric borate with 0.4% beta-phenylethyl alcohol.
      Viscosity of the eye drops was increased using polyvinyl alcohol. The drops,
      protected from light, were stored at the temperature of 4 degrees C and 20
      degrees C. As the criteria of the qualitative assessment of freshly prepared eye
      drops and during their storage, the following properties were considered:
      organoleptic analysis (color, clarity, and smell), sterility, pH, osmotic
      pressure, density, and viscosity, antimicrobial activity of cefuroxime and
      preservation efficiency of thiomersal and phenylmercuric borate in the eye drops.
      The storage temperature had a significant influence on the antimicrobial activity
      of the antibiotic in the eye drops. The antimicrobial activity of cefuroxime in
      the drops stored for 30 days at the temperature of 4 degrees C did not decrease.
      Thiomersal at the concentration over 0.003%, 0.005% benzalkonium chloride and
      0.01% chlorhexidine diacetate were not compatible with cefuroxime in the drops.

PMID- 17203868
TI  - Raloxifene does not affect the changes in bone histomorphometric parameters
      induced by low dose tacrolimus in male rats.
AB  - Raloxifene is a selective estrogen receptor modulator. The drug reduces bone loss
      and prevents fractures in postmenopausal women. Tacrolimus, an immunosuppressant,
      is used to prevent organ transplant rejection. The effect of raloxifene and
      tacrolimus on the osseous bone in men has not been exhaustively determined. To
      study the effects of raloxifene, tacrolimus as well as concurrent administration
      of raloxifene and tacrolimus on the osseous tissue in male rats, a preliminary
      assessment of the drug action on histomorphometric parameters of rat bones was
      made. The experiments were carried out on mature male Wistar rats. The animals
      were divided into six groups, 7 animals each: I--control rats; II--rats which
      were administered raloxifene (5 mg/kg po daily); III-- rats which were
      administered tacrolimus (0.3 mk/kg po daily); IV - rats which were administered
      tacrolimus (0.6 mg/kg po daily; V-- rats which were administered raloxifene (5
      mg/kg po daily) and tacrolimus (0.3 mg/kg po daily); VI - rats which were
      administered raloxifene (5 mg/kg po daily) and tacrolimus (0.6 mg/kg po daily).
      The drugs were administered for 4 weeks. Body mass, macrometric parameters of the
      tibia, femur and L-4 vertebra, histomorphometric parameters of tibia (transverse
      growth, width of osteoid, area of the transverse cross section of bone marrow
      cavity and cortical bone), and the femur (width of trabeculae, width of
      epiphyseal cartilage) were examined. The action of raloxifene in male rats was
      demonstrated through increased width of osteoid. An increased traverse growth of
      bone and osteoid width as well as transverse cross section of the cortical bone
      and the marrow cavity and increased thickness of trabeculae were observed in male
      rats receiving tacrolimus at 0.3 mg/kg. The administration of tacrolimus at 0.6
      mg/kg resulted in increased traverse growth of bone and increased thickness of
      osteoid, whereas the thickness of trabeculae remained unaffected. The results
      obtained in the rats administered concurrently raloxifene and tacrolimus (at 0.3
      mg/kg or at 0.6 mg/kg) were similar to those obtained in the group of rats
      receiving tacrolimus at 0.3 mg/kg. It seems that the most valuable in entire
      experimental system of the study are the results obtained in the group receiving
      tacrolimus at 0.3 mg/kg po, which are indicative of intensified bone remodeling
      processes with dominant the bone formation process.

PMID- 17203869
TI  - Black tea ameliorates aflatoxin-induced lipid peroxidation in the kidney of mice.
AB  - Oral administration of 25 and 50 mg of aflatoxin in 0.2 mL olive oil/animal/day
      for 30 days caused dose-dependent and significantly higher lipid peroxidation in
      the kidney of aflatoxin-treated mice than in the controls. The levels of non
      enzymatic antioxidant such as glutathione as well as the enzymatic antioxidants
      such as superoxide dismutase, glutathione peroxidase and catalase were
      significantly lower in the kidney of aflatoxin-treated mice than in the controls.
      Black tea extract (2%) treatment significantly ameliorates aflatoxin-induced
      lipid peroxidation, which could be due to higher enzymatic and non-enzymatic
      antioxidants in the kidney of mice as compared with that given aflatoxin alone.
      These findings suggest that black tea extract treatment significantly ameliorates
      aflatoxin-induced lipid peroxidation in the kidney of mice.

PMID- 17203870
TI  - The FAS-related apoptosis signaling pathway in the prostate intraepithelial
      neoplasia and cancer lesions.
AB  - An aim of the study was to determine the protein expression of the FAS-related
      apoptosis signaling pathway (FADD-FAS Associating Protein with Death Domain, PRO
      CASPASE-8 and CASPASE-8), which are responsible for signal transduction to
      trigger programmed cell death (apoptosis) in cancer and Prostatic Intraepitelial
      Neoplasia (PIN). 20 specimens from prostate cancer patients treated with radical
      prostatectomy were inwestigated. 8 cancers were diagnosed as G-2 and 12 as G-3.
      14 samples were described as poorly differentiated, high Gleason score (> or =
      7). Control group consisted of prostate specimens from autopsy of 3 young men.
      Specimens were fixed in 10% buffered formaldehyde and immersed in paraffin.
      Haematoxylin and eosin staining was done. Monoclonal antibodies to FADD & CASPASE
      8 (Novocastra, UK) were used to immunohistochemical study, according to
      streptavidine-biotin method. Semiquantitive method described protein expression.
      Expression index (EI) was calculated as a percent of positive FADD or CASPASE-8
      cells to total cells in the specimen. Statistical analysis was performed with the
      Student t-test (p < 0.05). Normal prostate tissue was negative in both, FADD and
      CASPASE-8 immunohistochemistry staining. PIN & prostate cancer lesions were found
      to strongly express of FADD & CASPASE-8 proteins. Expression of FADD in cancer
      lesions was 66,5+/-27,8% and 59,8+/-19,0% vs. 56,8114,8% HGPIN and LGPIN,
      respectively. Expression of CASPASE-8 in cancer lesions was 64,1 + 23,4% and
      61,5+/-15,0% vs. 48,0+/-17,6% HGPIN and LGPIN, respectively. PIN & prostate
      cancer lesions are characterized by similar high expression of proteins
      responsible for signal transduction to induce apoptosis. The mediators of
      apoptotic signal can be very important in prostate cancer prophylaxis and
      management.

PMID- 17203871
TI  - Flavonoid aglycones and phytosterols from the Erigeron acris L. herb.
AB  - Four flavonoid aglycones (apigenin, kaempferol, luteolin, quercetin) were
      isolated from methanolic extract from the herb of Erigemn acris L. (Asteraceae).
      In this extract five phytosterols (campesterol, chondrillasterol, stigmast-7-en-3
      ol(5alpha,3alpha), stigmasterol and spinasterone) were also identified.

PMID- 17203872
TI  - Estimation of DNA damage and cytotoxicity of anthracycline analogs in human
      melanoma cells on early and late passages.
AB  - Human malignant melanoma is a major problem characterized by both rapid rising
      incidence and strong chemoresistance. The aim of present experiments was to
      estimate the effects on DNA of new anthracycline analogs in melanoma cells
      obtained from various patients, cultured on early (E) and late (L) passages. For
      determination of cytotoxic effect, MTT assay was used and comet assay was used
      for the detection of DNA damage. The discrepancy between the intensity of DNA
      damage processes and IC50 values may indicate that there are some critical loci
      in the genome, responsible for cell death.

PMID- 17203873
TI  - [The modulatory effect of estrogen on the caudal trigeminal nucleus of the rat in
      an animal model of migraine].
AB  - Migraine is one of the most common neurological disorder affecting up to 14% of
      the population. The disease shows sexual dimorphism, thus gonadal steroids may
      play an important role in its pathophysiology. One model of migraine headache is
      the systemic administration of nitric oxide (NO) donor nitroglycerin (NTG), which
      triggers a delayed attack without aura in many migraine patients but not in
      healthy volunteers. NTG is also able to activate the neurons of the caudal
      trigeminal nucleus in the rat. In our review we summarise the effect of NTG on
      the expression of some molecules, in the superficial laminae of the spinal
      portion of trigeminal nucleus caudalis, which play an important role in the
      pathomechanism of headaches, and the modulatory effect of chronic estradiol
      treatment. Our data show that NTG was able to modify all the examined substances
      in the caudal trigeminal nucleus, while chronic estradiol treatment abolished
      this effect. These data may help to understand the mechanisms by which estrogens
      influence trigeminal nociception and how nitric oxide triggers migraine attacks.

PMID- 17203874
TI  - Animal models of Huntington's disease.
AB  - Huntington's disease is an autosomal dominantly inherited progressive
      neurodegenerative disorder. The main symptoms are choreiform, involuntary
      movements, personality changes and dementia. Huntington's disease is a member of
      a group of diseases caused by CAG repeat expansions. One research aim is to
      determine the earliest molecular changes associated with Huntington's disease.
      There is no possibility for this in humans, but various early changes have been
      identified in an animal model of Huntington's disease. They are constructed by
      excitotoxin causing striatal lesion, or mitochondrial toxins inducing energy
      impairment, or by generating transgenic mice.

PMID- 17203875
TI  - [Clinical analysis of patients with peripheral facial palsy].
AB  - Peripheral facial palsy is one of the most frequent neurological symptoms. In two
      thirds of the cases the cause is unknown, this is called "idiopathic peripheral
      facial palsy or Bell's palsy", but several different diseases have to be
      considered in the differential diagnosis. In this paper we reviewed the case
      histories of 110 patients treated for "peripheral facial palsy" in the Department
      of Neurology, Semmelweis University, Budapest in a five year period, 2000-2004.
      We studied the age, gender distribution, seasonal occurrence, comorbidities,
      sidedness, symptoms, circumstances of referral to the hospital, the initial
      diagnoses and therapeutic options. We also discuss the probable causes and
      consequences of diagnostic failures. RESULTS: the proportion of males and females
      was equal. There was no considerable difference between sexes regarding age
      distribution. Of the 110 patients 106 was diagnosed with idiopathic Bell's palsy,
      three cases with otic herpes zoster and one patient with Lyme disease. In our
      material, peripheral facial palsy was significantly more frequent in the cold
      period of late autumn, winter, and early spring. Diabetes mellitus and
      hypertension were more frequent than in the general population. 74% of the
      patients were admitted within two days from the onset of the symptoms. In 37%
      preliminary diagnosis was unavailable. In 15% cerebrovascular insult was the
      first, incorrect diagnosis, the correct diagnosis of "Bell's palsy" was provided
      only in 16%. The probable causes of diagnostic failures may be the misleading
      symptoms and accompanying conditions. We examined the different therapies applied
      and reviewed the literature in this topic. We conclude that intravenous
      corticosteroid treatment in the early stage of the disease is the therapy of
      choice.

PMID- 17203876
TI  - [Amyotrophic lateral sclerosis in Baranya county, Hungary].
AB  - Amyotrophic lateral sclerosis is a progressive neurodegenerative disease
      resulting in loss of upper and lower motoneurons. Here we analyzed the clinical
      and epidemiological data of 202 ALS patients admitted to our department between
      1950 and 2004. Risk and protective factors influencing onset and progression of
      the disease were examined. We also analyzed the relationship between first
      clinical symptoms/signs and prognosis of the disease. Our data suggest the
      importance of toxic factors in the initiation of the disease and the effect of
      clinical phenotype on the progression of ALS.

PMID- 17203877
TI  - [New methods in the investigation of brain hypoxia].
AB  - The main challenge is the investigation of mechanism for apoptosis research and
      the drug development. Mitochondria have a key position in the production of
      reactive oxygen species and in the evolution of apoptosis. More possible pathway
      will be known with the apoptosis investigation. For development of
      neuroprotective molecules could give strategies the investigation of apoptosis.
      Exact knowledge of apoptosis provides the possibility to screen new
      neuroprotective molecules. We developed a research assay, that could provide
      quantitative and qualitative data about the free radical production and the
      mitochondrial transmembrane potential using confocal microscopy. Thus, we could
      screen drug candidate, neuroprotective molecules.

PMID- 17203878
TI  - Movement-related beta responses in essential tremor and Parkinson's disease.
AB  - OBJECTIVE: To investigate the pathomechanism of essential (ET) and parkinsonian
      tremor (PT) by studying the correlation between tremor severity and movement
      related beta rhythm changes of the human electroencephalogram. PATIENTS AND
      METHODS: We recorded the electroencephalogram of 10 patients with essential
      tremor, 10 with Parkinsonian tremor and 10 controls. In a preliminary session we
      determined the side with lower and higher tremor intensity (T+, T++
      respectively), using accelerometry. Subjects pressed an on-off switch in a self
      paced manner with left and right thumb. After digitalization of the EEG from Cz,
      C3, C4 electrodes, the movement reactive beta frequency (MRBF), its
      minimum/maximum peak power values and their latencies triggered to movement
      offset were determined. RESULTS: The time course and amplitude of movement
      related beta desynchronization (ERD) were similar in each group regardless of
      tremor intensity. In ET tremor severity did not influence post-movement beta
      synchronization (PMBS) amplitude (PMBS(ET+) = 100.98 +/- 48.874%, PMBS(ET++) =
      135.1 +/- 92.87%; p = 0.231), however it was significantly delayed after the
      movement of the more tremulous hand (latPMBS(ET+) = 1.26 +/- 0.566 s,
      latPMBS(ET++) = 1.57 +/- 0.565 s, p = 0.003). In the PT group on the side of
      pronounced tremor the amplitude of PMBS decreased but it was not delayed,
      compared to the less affected hand (PMBS(PT+) = 115.19 +/- 72.131%, PMBS(PT++) =
      77.84 +/- 53.101%, p = 0.0028; latPMBS(PT+) = 1.4 +/- 0.74 s, latPMBS(PT++) =
      1.25 +/- 0.797 s, p = 0.191). In controls the power and latency of PMBS was
      similar on both sides. CONCLUSIONS: The results suggest that neuronal mechanisms
      underlying PMBS generation are differently affected by ET and PT. Investigation
      of PMBS might be used for the differential diagnosis of essential tremor and
      Parkinson's disease.

PMID- 17203879
TI  - [Biomechanics of intracranial aneurysms].
AB  - INTRODUCTION: Viscoelastic parameters of circumferential and meridional strips of
      ruptured and silent aneurysms were investigated (considered clinical and
      histological data either) in order to advance the prediction of risk of aneurysm
      rupture. METHOD: In our clinical practice, aneurysms managed by microsurgery
      aneurysm clipping were removed. Meridional and circumferential strips were cut.
      Strips were investigated by an uniaxial biomechanical instrument: distending
      force was recorded as the length of the strips was increased in steps. Normal
      stress-relaxation patterns were detected. The shape of strain curves well
      overlapped with the Standard Linear Solid Model curve, as had been expected. The
      viscosity, serial and parallel elastic moduli of the model were then computed.
      RESULTS: Linear correlation was demonstrated amongst peek distending force
      detected and aneurysm strip thickness. Steric inhomogeneity was detected at the
      meridional and circumferential strips. Strain-stress behaviour of ruptured and
      silent aneurysm specimen showed significant difference. Values of strips
      originated from patients suffered from hypertension as well as strips originated
      from aneurysms had been histologically found inflamed were higher. DISCUSSION:
      Results of these observations are going to be used to set three dimensional
      computer model in cooperation with IT team of Budapest University of Technology
      and Economics to advance rupture risk prediction.

PMID- 17203880
TI  - [Complex non-invasive hemodynamic system for the evaluation of vascular status].
AB  - The vascular diseases (myocardial infarct, stroke, peripheral occlusive disease)
      have a common pathophysiological background, the arteriosclerosis, that impairs
      the autoregulation of cerebral vessels, decreases the endothelium mediated flow
      in the peripheral vessels. Therefore the assessment of the vascular damage or the
      follow-up of therapy need a complex and simultaneous approach. Currently the
      morphological and functional changes in the vascular system can be investigated
      with separated measuring systems, focusing either to cardiac or cerebral
      parameters (intermittent blood pressure measurement, ECG, cerebral blood flow by
      transcranial Doppler e.g.). Our purpose is to establish a complex non-invasive
      system for the simultaneous measurement and comparison of
      cardiac/cerebral/peripheral hemodynamics. The hemodynamic parameters in
      hypertensive patients are examined with transcranial Doppler and cardiac
      monitoring during tilt-table test. Intima-media thickness, flow-mediated
      dilatation in brachial artery, augmentation index and pulse wave velocity are
      also measured. The measurement will be repeated after 6 and 12 months follow-up.
      Our preliminary results are similar to those found in the literature, that proves
      the reliability of our complex noninvasive hemodynamic system. It is assumed,
      that 12 months antihypertensive therapies with ACE inhibitors, calcium antagonist
      etc. might result in different effects on different vascular parameters. Our
      system enables the individualization of antihypertensive therapy.

PMID- 17203881
TI  - [The role of tremorometry in predicting the outcome of ablative surgeries].
AB  - Ablative neurosurgical interventions are widely used for the treatment of
      advanced Parkinson's disease. However, in some cases, the achieved result is
      temporary and repeat operation is necessary to obtain a permanent effect. By
      analyzing 30 ablative surgeries using comparative accelerometry, we looked for a
      biological marker predicting the efficiency. In 27 cases where clinical symptoms
      were permanently improved, a significant increase in rest tremor frequency was
      observed in addition to reduction in tremor intensity. In contrast, in those
      three cases where the clinical effect of the surgery was only temporary, the
      frequency of tremor remained unchanged despite of the transitory decrease in
      intensity. We thus hypothesize that postoperative change in frequency of tremor
      but not the intensity may predict the outcome of ablative treatments.

PMID- 17203883
TI  - [Epidemiology of stroke in the elderly].
AB  - BACKGROUND: In the industrialized countries the very old stroke patient is more
      frequent than before. For the time being Japanese people have the highest
      expected lifespan, so the epidemiological features of stroke in the very old can
      be examined here quite easily. From a few publications with low case number it is
      known that in this group of patients the statistical characteristics of stroke is
      remarkably different from the younger ones. SUBJECTS AND METHODS: The subjects
      aged 85 or more years were selected from the Akita Stroke Registry with first
      ever acute stroke from 1996 to 1998. RESULTS: 8046 cases were recorded. There
      were 7362 patients aged <85 years, and 684 patients aged > or =85 years (8.5%).
      Sex ratio (women/men) was 1.89 in the two age groups. In the population of Akita
      the crude incidence of first-ever stroke was 222/100,000/year, and
      1085/100,000/year in the very old, who were characterized with relatively lower
      prevalence of stroke risk factors, except that of atrial fibrillation (26.9%) and
      cardiac diseases (34.2%). The stroke subtype distribution (cerebral infarction
      73.2%, intracerebral haemorrhage 20.6%, subarachnoidal haemorrhage 6.1%) was
      significantly different from the one known in Japan. Mortality rates were
      considerably high, especially in the SAH group. The most powerful prognostic
      factor of death was the level of consciousness at the onset. The next in the
      order of predicting value was the SAH subtype. CONCLUSION: While people aged 85
      years or more had relatively lower prevalence of cardiovascular risk factors,
      they suffered stroke with very high frequency, the evolved cerebrovascular event
      caused very severe symptoms and led to death with high rate. Implicitly this is
      illuminating the complexity of aging as a process, furthermore it increases the
      importance of prevention, and even more of the care and rehabilitation of acute
      stroke in this old age group.

PMID- 17203882
TI  - [Long-term application of the multiple sclerosis functional composite test in
      Debrecen, Hungary].
AB  - INTRODUCTION: The multiple sclerosis functional composite (MSFC) has been
      recommended by the National Multiple Sclerosis Society as a new clinical outcome
      measure. It is based on measurements in three clinical dimensions: leg
      function/ambulation (timed 25-foot walk), arm function (9 hole peg test) and
      cognitive function (paced auditory serial addition test). Scores on component
      measures are converted to standard scores (Z-scores), that reflect patient
      performance. This method has not yet been introduced into routine clinical
      practice. PATIENTS AND METHODS: Since March 2000 over the five years period the
      MSFC calculation was applied to 17 patients with relapsing-remitting multiple
      sclerosis (age mean: 37.4 +/- 10.8 years, duration of the disease: 5.5 +/- 4.9
      years, EDSS: 2.7 +/- 1.4) seen at the neuroimmunological outpatient clinic to
      evaluate its usefulness and its correlation with the traditionally applied
      expanded disability status scale (EDSS). Thirteen patients received
      immunomodulatory treatment (interferon beta and glatiramer acetate), one patient
      received immunosuppressant therapy (azathioprine), and there was one patient, who
      developed secondary-progressive phase and we changed the interferon treatment to
      mitoxantrone. MSFC and EDSS were measured at 3., 6., 9, 12., 18 and 60 months of
      follow-up. RESULTS: The prospective study confirmed a strong correlation between
      EDSS and MSFC in multiple sclerosis. The MSFC was more sensitive to clinical
      changes than EDSS. Our results after 18 months of follow up are already
      published. After five years arm/hand function and leg function/ambulation were
      the most sensitive measures for disease progression. In contrast with the
      literature we did not experience correlation with cognitive changes.
      CONSEQUENCES: We demonstrated strong correlation between MSFC and EDSS after a
      longer period. MSFC is a simple method, suitable for follow-up of multiple
      sclerosis patients in everyday clinical practice.

PMID- 17203884
TI  - [Thoracic meningocele].
AB  - Herniation of the meninges through a defect of the spinal canal is a spinal
      meningocele, and is usually located dorsally in the lumbosacral region.
      Meningoceles are usually part of a complex developmental disorder, or of a
      systemic disease, or it can be iatrogenic, as well. We report a very rare case of
      a true anterior thoracic meningocele.

PMID- 17203885
TI  - [Report of the Hungarian Epilepsy League].

PMID- 17203886
TI  - Bone marrow-derived cells: roles in solid tumor. Minireview.
AB  - The role of cancer stem cells has been demonstrated for some cancers. Recently,
      research indicated that solid tumors may originate from bone marrow stem cells.
      Bone marrow-derived cells have recently been shown to contribute to stromal
      formation, especially angiogenesis and lymphvasculogenesis. Moreover, the
      interaction and the cell fusion between cancer cells and bone mesenchymal stem
      cells could enhance the aggregative ability of cancer cells. Bone marrow derived
      cells home to tumor-specific pre-metastatic sites to provide a permissive niche
      for incoming tumor cells. Since bone marrow-derived cells play an important role
      in carcinogenesis, angiogenesis and metastasis, bone marrow-derived cells are not
      only the tool for cancer therapy, but also the targets for cancer therapy.

PMID- 17203887
TI  - Radiotherapy combined with hormonal therapy (RT-HT) in prostate cancer patients
      with low, intermediate, and high risk of biochemical recurrence: perspective and
      therapeutic gain analysis.
AB  - Treatment of prostate cancer (PC) is a challenge for both urologists and
      radiation oncologists. Currently, two radical methods of treatment are
      recommended in localized prostate cancer (PC)--i.e. radical prostatectomy (RP)
      and radiotherapy (RT) with excellent long-term results. However, the outcome of
      RT, which is the treatment of choice in locally advanced stages of the disease,
      is unsatisfactory due to the high risk of regional or distant metastases and
      local failure. Lately, hormonal therapy (HT), which had mainly been indicated for
      treatment of patients with distant metastases, has been added to radiotherapy to
      improve the efficacy of treatment. The general rationales for combining RT and HT
      are four-fold: decreasing prostate gland volume, diminishing the number of cancer
      cells, improving tumor oxygenation, and eliminating distant and regional
      micrometastases. Over the last 20 years several randomized clinical trials
      evaluating the results of combined HT and RT treatment have been carried out. The
      RTOG 85-31, RTOG 86-10, EORTC 22863 and RTOG 92-02 trials were completed from the
      mid 80s to the mid 90s and long-term follow-up data on all important end-points
      are now available. These data have been evaluated by panels of experts and served
      as the basis for the latest American (NCCN 2005) and European (EAU 2005)
      recommendations on prostate cancer. However, despite the long-term results of
      these trials, there are still no clear-cut answers to the following crucial
      questions: What is the optimal timing of hormonal therapy? What types of patients
      can benefit most from combined strategies? What is the spectrum and potential
      reversibility of side effects of long-term combined treatment? How does it
      influence the patients quality of life and care costs? Other questions concern
      the possible role of androgen deprivation therapy combined with brachytherapy.
      The only randomized trial to evaluate this issue to date was stopped due to
      incomplete accrual. Therefore, answers must be sought in the large body of
      nonrandomized studies. There is a constant need for properly designed randomized
      clinical trials to precisely identify the subgroup of patients who will benefit
      most from combined RT and HT treatment. Results of ongoing clinical trials (RTOG
      9901, RTOG 9408) are expected to yield some answers to the questions mentioned
      above. Currently, we can conclude that in the group of patients with high risk of
      relapse (T3 or GS > 7 or PSA >20 ng/ml), combined hormonal and radiation therapy
      improves prostate cancer treatment results and should be highly recommended.

PMID- 17203888
TI  - New [1,2,4]triazolo[4,3-c]quinazoline enhances cisplatin- and temozolomide
      induced growth inhibition and apoptosis in HL-60 cells.
AB  - The purpose of this study was to investigate the therapeutic potential of a newly
      synthesized [1,2,4]triazolo[4,3-c]quinazoline (NTCHMTQ) alone and in combination
      with two anticancer drugs (cisplatin and temozolomide) against HL-60 leukemia
      cell line. The IC50 value of NTCHMTQ toward HL-60 cells was 19.7 microM. No
      apoptosis and cell cycle changes were observed in cells treated with 5 microM
      NTCHMTQ alone. Combination of non-toxic concentrations of NTCHMTQ (1-5 microM)
      with cisplatin or temozolomide sensitized HL-60 cells to these two drugs and
      significantly enhanced their efficacies, that is illustrated by combination
      indexes, sub-G0 cell fraction, apoptotic DNA fragmentation and caspase-3
      activity. The results suggest that combined therapy of non-toxic concentrations
      of NTCHMTQ with chemotherapeutics may provide synergistic regimen for treatment
      of leukemia. However, further in vitro and in vivo experimental drug-cell and
      drug-drug studies are warranted.

PMID- 17203889
TI  - The AFT024 stromal cell line improves MDR1 gene transfer to CD34+ cells derived
      from human umbilical cord blood.
AB  - Human hematopoietic stem cells (HSCs) are difficult to transfect with retroviral
      vectors because of their quiescent nature. Based on the theory that the murine
      fetal stromal cell line AFT024 can recruit significant numbers of HSC into cell
      cycle without loss of their primitive function, we transduced human umbilical
      cord blood cells (UCB) derived CD34+ cells with a retroviral vector pHaMDR1/A
      containing the human multidrug resistant 1 gene (MDR1) during co-culture with the
      AFT024 feeders. We found that the presence of the AFT024 cells increased the
      proportion of Rh-123dull cells up to 35.5%+/-11.4% and transduced colony-forming
      cells (CFCs) up to 15.2%. Six weeks after transplantation of 5x10(4) day 0
      uncultured CD34+ HSCs or their equivalents expanded in the presence or absence of
      the AFT024 cells for 21 days into non-obese diabetic/severe combined
      immunodeficient (NOD/SCID) mice, we found that CD34+ cells expanded in the
      presence of the AFT024 cells engrafted in each receptor mouse and the percentage
      of CD45+ cells reached 18.8%+/-9.5%, of which 18.1%+/-6.0% were Rh-123dull cells.
      These results suggest that the AFT024 stromal cells can significantly improve
      MDR1 gene transfer efficiency and maintain the engrafting ability of the CD34+
      HSCs derived from UCB.

PMID- 17203890
TI  - Mitochondrial transmembrane potential in spontaneous and camptothecin-induced
      apoptosis of melanotic and amelanotic melanoma cells.
AB  - In this work we tried to estimate the role of mitochondria in the ability of
      cells of two: melanotic and amelanotic transplantable melanoma lines to undergo
      spontaneous and camptothecin-induced apoptosis. We measured mitochondrial
      transmembrane potential (DeltaPsi) changes during culture without (spontaneous
      apoptosis) and with camptothecin (induced apoptosis) by using JC-1 staining and
      flow cytometry analysis. Cytochrome c release and PARP cleavage as the biological
      effects of DeltaPsim changes belonging to the phenomena observed during apoptosis
      were estimated by Western blotting. The results of our investigations showed in
      both transplantable melanoma cells the features indicating apoptosis: DeltaPsi
      changes, cytochrome c release and PARP cleavage, but the degree of observed
      changes depended on the phenotype of melanoma cells examined. After camptothecin
      treatment the changes were more pronounced in the amelanotic melanoma cells- the
      more aggressive line.

PMID- 17203891
TI  - Prognostic significance of clusterin immunoreactivity in breast cancer.
AB  - Clusterin (CLU) is involved in a variety of biological processes and has been
      found to be expressed even in many human malignancies, including breast cancer.
      Currently, there are only few data on the prognostic value of CLU in breast
      cancer. We therefore evaluated the relationship between CLU expression and
      clinicopathological parameters as well as relapse-free survival (RFS) and
      metastasis-free survival (MFS) of 141 breast cancer patients using the monoclonal
      antibody 7D1. CLU expression was found in 26% of cases and correlated
      significantly with high histological tumor grade and high Ki-67 labeling index
      (p=0.026 and p=0.010, respectively). Univariate Cox regression analysis revealed
      that CLU expression was tendentiously associated with RFS (p=0.068; relative risk
      [RR]: 1.77) and MFS (p=0.122; RR: 1.57). In a multivariate analysis, tumor grade,
      stage, estrogen receptor status and patients age (concerning RFS) as well as
      grade and lymph node status (concerning MFS) were identified as significant
      independent prognosticators. CLU expression showed an independent prognostic
      relevance concerning prediction of RFS by trend (p=0.110; RR: 1.81). We conclude
      from our data that estimation of CLU immunoreactivity may be helpful as a
      supplementary criterion to better assess the tumors propensity to relapse in
      selected cases of breast carcinoma.

PMID- 17203892
TI  - Independent origin of 185delAG BRCA1 mutation in an Indian family.
AB  - BRCA1 and BRCA2 are the two major breast cancer susceptibility genes. We tested
      members of a family with multiple cases of breast cancer, for mutations in the
      BRCA1 gene. Analysis of the PCR amplicons of all the exons (22) of the BRCA1 gene
      using conformation sensitive gel electrophoresis (CSGE) revealed a heteroduplex
      band pattern in exon 2 of the proband (III-3) in this family. The amplicon was
      further sequenced to assess the nature of the mutation, which revealed a deletion
      of AG nucleotides at the 185th position (185delAG). The two base pair deletion
      introduces a stop codon at the 39th amino acid residue. A similar analysis was
      carried out on other extended family members to evaluate their allelic status. We
      detected the same deletion in 7 of the 19 members tested. Two of them are males.
      Haplotype analysis suggested an independent origin for this mutation. Our study
      highlights the importance of testing hereditary cases of breast/ovarian cancer
      for BRCA1 mutations in extended families in order to identify high-risk
      individuals at a pre-clinical stage and provide genetic counseling.

PMID- 17203893
TI  - Fine-needle aspiration biopsy-RT-PCR expression analysis of prothymosin alpha and
      parathymosin in thyroid: novel proliferation markers?
AB  - Fine-needle aspiration biopsy-based cytology has become an established and
      reliable diagnostic preoperative test in the evaluation of thyroid nodules.
      Despite the high specificity and sensitivity of the method, results might be
      doubtful in a significant number of cases. Genetic analysis of the aspirates by
      RT-PCR may contribute, in parallel to the cytology report, to a more precise
      diagnosis. Prothymosin alpha and parathymosin are two homologous chromatin
      remodeling proteins essential for cell cycle progression and proliferation of
      either normal or malignant cells. A semi-quantitative RT-PCR assay was developed
      to determine prothymosin alpha and parathymosin mRNA expression patterns in
      thyroid follicular cells obtained from the fine-needle aspiration biopsy
      specimens of patients diagnosed with simple nodular goitre, follicular adenoma,
      papillary and follicular well-differentiated carcinomas. Prothymosin alpha and
      parathymosin mRNA levels were found significantly elevated in well-differentiated
      carcinomas in relation to adenomas (p<0.05) and goitres (p<0.05), an event
      possibly linked to the proliferation activity of thyroid follicular cells.
      Further studies are required to establish prothymosin alpha and parathymosin as
      diagnostic proliferation markers in thyroid cancer, especially in cases of
      undetermined cellular morphology of follicular origin which reflect the most
      common cytohistopathological discrepancies.

PMID- 17203894
TI  - Longterm treatment results of childhood medulloblastoma by craniospinal
      irradiation in supine position.
AB  - Medulloblastoma, a primitive neuroectodermal tumor growing in cerebellum, is one
      of the most sensitive to radiation therapy childhood brain tumors. The
      radiotherapy is an essential method of treatment for these tumours, but the
      surgery is the primary treatment of choice in medulloblastoma. I this study
      between January 1997 and March 2005 were post-operative irradiated a total number
      of 33 pediatric patients aged under 15 years (median age 8.7 years) with
      medulloblastoma. All tumors were histologically proved and were localizated
      infratentorially in the posterior fossa. All of the patients were irradiated with
      a dose of 24-36 Gy to the whole craniospinal axis and boost with conformal
      therapy restricted to the tumor bed to the total dose of 50-54 Gy (30-36 Gy "high
      risk", 24-30 Gy "standard risk" group). Chemotherapy received 26 patients (78%).
      Patients with craniospinal irradiation were placed in supine position and fixed
      by a vacuum-form body immobilizer and head mask. Irradiation was performed using
      standard fractionation (5 fractions per week) with a single dose of 1.5-1.8 Gy
      for craniospinal axis by photon beam (6 MV) of the linear accelerator. The median
      overall survival for the whole group was 55.3 months. The median of disease-free
      survival was 20.6 months, 8 patients (24%) died. In our study the statistical
      difference in survival rate between standard and high-risk patients with
      medulloblastoma was not shown. No relationship was found between survival and
      age, sex or tumor size. Endocrine deficits occurred in 45% (8 patients of the
      group were hypothyroid, 6 patients needed growth hormone replacement therapy, 1
      patient had early puberty). This results (results of overall and disease-free
      survival) and side-effects of technique of craniospinal axis irradiation in
      supine position are comparable with results of technique in prone position.
      Further evaluation of the effectiveness of our therapy is not feasible due to the
      small number of patients.

PMID- 17203896
TI  - Difficulties in the diagnosis of intracystic tumors of the female breast.
AB  - The objective of the current study was to determine the accuracy of radiological
      and cytological diagnoses of intracystic and papillary lesions in distinguishing
      between true papillary benign and malignant lesions. Seventy cytological reports
      of intracystic proliferations were selected from our cytopathological database at
      the Breast Health Corporation, Budapest, Hungary, dating back to the last 7
      years. Retrospective analysis of the diagnostic approaches--mammography,
      ultrasonography, clinical examination and cytology--was performed in selected
      cases. The results of imaging and cytological examination are routinely reported
      on a categorical scale ranging from 1 to 5. 44 patients underwent surgical
      excision: histology showed benign lesions in 21 and malignant lesions in 23
      cases. Twelve patients, who did not undergo biopsy and presented a stable disease
      at follow-ups, were also included in the group of benign lesion. Fifteen patients
      were not available for follow-up. Concerning the total investigated cases the
      mean categorical values of mammography, ultrasonography and cytology were 2.24,
      2.78 and 3.05 respectively. The malignant and benign groups significantly differ
      from each other concerning the mean age of the patients (p=0.0216), the
      distribution of the coded mammographical results (p= 0.0171) the cytological
      results (p=0.0001), and average tumor size measured on mammogram images
      (p=0.0199). The two group does not significantly differ over the distribution of
      mammographical density patterns (p=0.1075), radiomorphological appearance
      (p=0.1101), average tumor size measured on ultrasonography (p=0.2665), and
      patient complaints (p=0.2634). The evaluation of ultrasonography shows borderline
      significance (Pearson Chi-square test: p=0.0616, M-L Chi-square test: p=0.0404)
      between the malignant and benign groups. Differential diagnosis between malignant
      and benign intracystic and papillary lesions is feasible using common
      radiological diagnostics. However, more efficient teamwork is needed with the
      cooperation of a well-trained cytologist and radiologist, who are able to produce
      precise images of the lesions, and guides the aspiration of the adequate samples
      for cytology, which is the most valuable examination.

PMID- 17203895
TI  - In vitro and in vivo antileukemic effect of novel dimers consisting of 5
      fluorodeoxyuridine and arabinofuranosylcytosine.
AB  - Various amphiphilic heterodinucleoside phosphates containing 1-beta-D
      arabinofuranosylcytosine (ara-C) and 5- fluorodeoxyuridine (5-FdUrd) have
      recently been synthesized in order to increase the efficacy of ara-C and 5-FdUrd.
      Employing growth inhibition and growth recovery assays, we evaluated the in vitro
      effects of four of these dimers (No. 2, 2A, 3, 10) in L1210 and P388D1 murine
      leukemia cells. Although ara-C and 5-FdUrd appeared equimolar in all dimers,
      their contribution to the cytotoxicity of these agents was different. Thus, the
      liberation of ara-C and 5-FdUrd from their dimeric origin and their subsequent
      metabolic activation had a different course. In another set of experiments, we
      examined the in vivo effects of these agents in mice. The dimer with the highest
      cytotoxicity in vitro exerted the lowest acute toxicity and yielded the lowest
      therapeutic effect in vivo. The obtained data indicate that dimers with slower
      liberation of ara-C and 5-FdUrd were less cytotoxic, but prolonged liberation of
      both antimetabolites protected them from inactivation and extended the time
      period of therapeutic action. Some of the dimers exceeded the synergistic effects
      yielded by simultaneous application of both ara-C and 5-FdUrd. The significantly
      higher therapeutic potential of these new antitumor agents indicates that further
      studies are warranted.

PMID- 17203897
TI  - Interactions between smoking and other exposures associated with lung cancer risk
      in women: diet and physical activity.
AB  - The objective of the study is to estimate the differences in the impact of diet
      and physical exercise on lung cancer risk in female nonsmokers vs. smokers, and
      reveal interactions, if any. In a hospital based case-control study, data
      collected by in-person interviews from 569 female lung cancer cases and 2120
      controls were analyzed using unconditional logistic regression stratifying by
      appropriate factors. Protective effects were observed for intake of milk/dairy
      products (OR=0.57, 95%CI 0.35-0.94), vegetables (OR=0.60, 95%CI 0.40-0.91),
      apples (OR=0.69), wine (OR=0.77), and physical exercise (OR=0.59, 95%CI 0.42
      0.83) among smokers only, while no similar effects were found among nonsmokers.
      In contrast, the intake of black tea was associated with a protective effect
      (OR=0.66, 95%CI 0.47-0.94) among nonsmokers only. Comparing the effects of
      dietary items and physical activity on lung cancer risk among nonsmokers versus
      smokers, statistically significant effect modifications were found for black tea
      (P 0.005), and milk/dairy products (P 0.047). Borderline effect modifications
      emerged for physical exercise (P 0.077). CONCLUSIONS: These results indicate
      protective effects of some components of healthful diet and physical exercise
      among smokers, and of the intake of black tea among nonsmokers. The observed
      interactions of the impact of black tea, milk/dairy products and physical
      activity upon lung cancer risk in women at different levels of the smoking habit
      deserve further studies.

PMID- 17203898
TI  - [The value of dynamic cervical MRI in management of selected patients presenting
      traumatic cervical cord injury].
AB  - OBJECTIVE: The purpose of this report is to describe our experience with dynamic
      cervical MRI for detection of cervical spinal cord instability in patients
      presenting spinal cord trauma without fracture or dislocation of the spinal
      column. MATERIAL AND METHODS: Since January 2000 a total of 95 patients
      presenting spinal cord trauma have been treated in our department. All patients
      underwent MRI for diagnostic work-up. Dynamic MRI was performed if spinal cord
      instability was suspected. Whenever possible, high-quality plain radiography
      dynamic views were obtained (coma, severe deficit, study of the cervicothoracic
      junction). RESULTS: Dynamic MRI allowed diagnosis of spinal cord instability in 6
      patients with a mean age of 65 years (range, 45 to 75). Instability occurred
      during extension in 4 patients and during flexion and extension in one case. In
      the remaining case instability was associated with herniation of a cervical disc
      due to a severe cervical sprain. All 6 patients underwent early surgical
      stabilization that allowed improvement in-hospital patient care and quick
      transfer to rehabilitation centers. CONCLUSION: Dynamic MRI can be a useful tool
      to detect unstable spinal cord instability in some patients presenting
      noncompressive spinal cord injuries.

PMID- 17203899
TI  - [Venous embolization of dural arterio-venous fistulas. Transcranial approach
      under neuronavigation].
AB  - OBJECT: Transvenous embolization is an effective treatment for dural arterio
      venous fistulas. In the event of dural sinus thrombosis, embolization can be
      performed by direct puncture via craniectomy. We report our experience with
      transcranial venous embolization in two patients. METHODS: Two patients underwent
      transcranial venous embolization of a type-III dural arterio-venous fistula of
      the transverse sinus. The craniectomy was performed with neuronavigation
      assistance. RESULTS: The surgical approach consisted in a minimal exposure of the
      sinus with a drill. Neuronavigation allowed accurate placement of the
      craniectomy. The endovascular treatment was performed in a second stage, enabling
      complete and stable occlusion of the fistula in both patients. CONCLUSION: This
      combined treatment of dural AVFs associating craniectomy and transcranial
      puncture of the sinus is simple and efficient when retrograde navigation through
      the internal jugular vein cannot be achieved. Neuronavigation is helpful in
      accurately positioning the craniectomy.

PMID- 17203900
TI  - Enlargement to a saccular aneurysm and subsequent rupture of infundibular
      widening of posterior communicating artery.
AB  - A small dilatation known as infundibular widening (IFw) is frequently seen (7%
      25%) on the posterior communicating artery (PComA) at its origin from the
      internal carotid artery. Development and subsequent rupture of an aneurysm on a
      previously radiographically demonstrated IFw has rarely been documented. We
      present two patients who suffered from subarachnoid hemorrhage (SAH). Initial
      cerebral angiography demonstrated IFw on PComA. They were readmitted to the
      hospital 9 and 11 years later, after a new SAH. Repeated cerebral angiography
      revealed an aneurysm arising from the site where the IFw had been seen previously
      in both cases. The aneurysms were clipped with favorable outcome. This report
      adds two new cases documenting enlargement of PComAIFw into an aneurysm. Patients
      with PComAIFw, especially those who have experienced SAH, should be considered
      for periodic follow-up to rule out the development of an aneurysm over time.

PMID- 17203901
TI  - [Capillary hemangioma of the ethmoid sinus. Case report and review of the
      literature].
AB  - We report the rare observation of a 38-year-old man diagnosed with capillary
      hemangioma exclusively involving the ethmoid sinus. Complete resection was
      obtained via ethmoid endoscopy combined with an intracranial approach. Capillary
      hemangioma is a rare and benign vascular tumor in adults primarily developing in
      the skin and subcutaneous tissues of the head and neck, and/or within oral and
      nasal cavities. No hemangioma exclusively involving the ethmoid sinus has been
      previously reported. Complete resection is the treatment of choice, providing a
      favorable prognosis with low risk of recurrence.

PMID- 17203902
TI  - [Dumbell hemangioblastoma of the eighth cervical nerve root].
AB  - Hemangioblastomas involving cervical nerve roots are extremely rare. Only one
      case has been previously reported in the literature. We report the case of a 33
      year-old man presenting with a 6-month history of upper limb pain. MRI and
      cervical angiography demonstrated the presence of a dumbell (intra and
      extradural) and highly vascularized tumor of the right C7-T1 foramina.
      Histological examination eventually confirmed the diagnosis of hemangioblastoma.
      Total removal of such a lesion may require combined (anterior and posterior)
      approaches and preoperative embolization.

PMID- 17203903
TI  - [Late cervicodorsal metastasis of thyroid adenocarcinoma treated by anterior
      cervicotomy].
AB  - Metastasis from a thyroid adenocarcinoma is a rare entity with high mortality. We
      describe an unusual case in a woman displaying tetraparesis due to a late cervico
      dorsal metastasis operated on via a simple anterior cervicotomy. Outcome was good
      at eighteen months follow-up. The histological diagnosis was follicular
      adenocarcinoma. The development of a vertebral metastasis from a thyroid
      adenocarcinoma 11 years after the treatment of the primitive cancer is rare. The
      anterior cervico-dorsal location in this patient required decompression via an
      anterior approach. Surgical treatment of the tumor and spinal stabilization were
      possible via a simple anterior cervicotomy which allowed adequate access to the
      third thoracic vertebra, without sternotomy or thoracotomy.

PMID- 17203904
TI  - [Chronic intramedullary abscess (Streptococcus sanguis). A case report and review
      of the literature].
AB  - OBJECTIVE: Chronic intramedullary spinal cord abscesses are very rare. We present
      here a new case of this pathology, revealed by a progressive spinal cord
      compression. This case is particular because of the long follow up before surgery
      (two years). CASE REPORT: This 69-year-old patient presented a gradually
      progressive paraparesis and sensory loss associated with leg pain. The past
      medical history was dominated by a epidermoid cancer of the tongue. MRI showed an
      intramedullary mass at T10. On the T1-weighted sequences, the lesion was
      isointense with the spinal cord, Gadolinium infusion showed homogeneous
      enhancement of the lesion. T2-weighted sequences showed decreased signal within
      the lesion and an increased signal peripherally (edema). Corticosteroid infusions
      relieved the symptoms so the patient declined surgery. Two episodes of regressive
      paraplegia were treated by the same infusions. The patient accepted surgery after
      a third episode. RESULTS: The intervention was performed two years after the
      first signs and revealed a hard white mass attached to the spinal cord.
      Pathologic examination showed infectious inflammation. Bacteriological cultures
      found a Streptococcus sanguis. Two years later the patient could walk; a minimal
      deficit persists. CONCLUSION: First, the diagnosis was evoked but not retained
      because of the long course. The corticosteroid infusions gave relief and did not
      increase the deficit. The MRI findings remained unchanged. Intramedullary spinal
      cord abscesses are very rare. This pathology must be recognized because without
      treatment morbidity is high with a potentially fatal outcome.

PMID- 17203905
TI  - [Postoperative meningitis caused by an unusual etiological agent: Salmonella
      enteritidis].
AB  - Salmonella intracranial infections are unusual in adults, and particularly after
      neurosurgical procedures. We report a case of post-operative meningitis owing to
      Salmonella enteritidis. A 72-year-old man with type 2 diabetes was admitted to
      our unit for postoperative evaluation and management after neoplasic intracranial
      surgery. On the third day of admission, the patient developed infectious signs
      and diagnosis of postoperative meningitis was evoked. The cultivation of
      cerebrospinal fluid revealed Salmonella enteritidis which was also identified in
      several blood cultures. The treatment consisted of third-generation cephalosporin
      and quinolone to which Salmonella enteritidis was susceptible. However, the
      clinical course was poor and the patient died on day 8. This case demonstrates
      that postoperative meningitis can be caused by an unusual agent like Salmonella
      enteritidis.

PMID- 17203906
TI  - [Intradiploic encephalocele in an adult. A case report and review of the
      literature].
AB  - We describe a rare case of parietal intradiploic encephalocele in a 51-year-old
      woman with no history of head trauma. The patient presented with a 1-month
      history of left hemiparesthesia. A hard indolent scalp lesion was palpable on
      examination in the right parietal area. Skull x-rays and cranial computed
      tomography examination demonstrated a lytic lesion that was consistent with a
      malignant osteolytic skull lesion. Magnetic resonance imaging of the head
      revealed an intradiploic cyst that included a round tissue mass contiguous with
      the parietal cortex. Surgery confirmed the diagnosis of encephalocele and the
      patient underwent surgical resection of the herniated brain, duraplasty, and
      cranioplasty. The presenting hemiparesthesia persisted at the 6-month follow-up.
      Encephaloceles of the cranial vault are a rare complication of skull fractures
      and rarely occur in adults. These lesions can be difficult to distinguish from
      congenital encephaloceles in patients with no history of head trauma. The
      pathogenesis, clinical and radiological nuances and the role of surgery are
      discussed.

PMID- 17203907
TI  - [Dendritic cells and gliomas: a hope in immunotherapy?].
AB  - Immunotherapy has been explored for several decades to try to improve the
      prognosis of gliomas, but until recently no therapeutic benefit has been
      achieved. The discovery of dendritic cells, the most potent professional antigen
      presenting cells to initiate specific immune response, and the possibility of
      producing them ex vivo gave rise to new protocols of active immunotherapy. In
      oncology, promising experimental and clinical therapeutic results were obtained
      using these dendritic cells loaded with tumor antigen. Patients bearing gliomas
      have deficit antigen presentation making this approach rational. In several
      experimental glioma models, independent research teams have showed specific
      antitumor responses using these dendritic cells. Phase I/II clinical trials have
      demonstrated the feasibility and the tolerance of this immunotherapeutic
      approach. In neuro-oncology, the efficiency of such an approach remains to be
      established, similarly in oncology where positive phase III studies are missing.
      Nevertheless, dendritic cells comprise a complex network which is only partially
      understood and capable of generating either immunotolerance or immune response.
      Numerous parameters remain to be explored before any definitive conclusion about
      their utility as an anticancer weapon can be drawn. It seems however logical that
      immunotherapy with dendritic cells could prevent or delay tumor recurrence in
      patients with minor active disease. A review on glioma and dendritic cells is
      presented.

PMID- 17203908
TI  - [Good practice: a guide for neurosurgeons].

PMID- 17203909
TI  - Noise in animal facilities: why it matters.
AB  - Environmental noise can alter endocrine, reproductive and cardiovascular
      function, disturb sleep/wake cycles, and can mask normal communication between
      animals. These outcomes indicate that noise in the animal facility might have
      wide-ranging affects on animals, making what laboratory animals hear of
      consequence for all those who use animals in research, not just the hearing
      researcher. Given the wide-ranging effects of noise on laboratory animals,
      routine monitoring of noise in animal facilities would provide important
      information on the nature and stability of the animal environment. This special
      issue will highlight the need for more thorough monitoring and will serve as an
      introduction to noise and its various effects on animals.

PMID- 17203910
TI  - The fundamentals of sound and its measurement.
AB  - The purpose of this article is to provide directors of animal care facilities
      with a basic understanding of some of the principles of acoustics and the
      measurement of sound. This knowledge likely will enable directors to work
      effectively with sound and hearing specialists at their institutions to monitor
      and control the acoustic environments of laboratory animal facilities.

PMID- 17203911
TI  - Hearing ranges of laboratory animals.
AB  - Any attempt to assess the effects of sounds on animals must consider species
      differences in hearing abilities. Although the hearing ranges of most species
      overlap to a large degree, considerable variation occurs in high- and low
      frequency hearing as well as in absolute sensitivity. As a result, a sound that
      is easily audible to one species may be less audible, or even inaudible, to
      another. The purpose of this review is to describe the variation in the hearing
      ranges of common laboratory animals.

PMID- 17203912
TI  - Factors affecting hearing in mice, rats, and other laboratory animals.
AB  - The auditory system of rodents and other animals is affected by numerous genetic
      and environmental variables. These include genes that cause hearing loss,
      exposure to noise that induces hearing loss, ameliorative effects of an augmented
      acoustic environment on hearing loss, and effects of background noise on arousal.
      An understanding of genetic and environmental influences on hearing and auditory
      behavior is important for those who provide, use, and care for laboratory
      animals.

PMID- 17203913
TI  - Types and functions of ultrasonic vocalizations in laboratory rats and mice.
AB  - Many laboratory rodents emit ultrasonic vocalizations. The purpose of this review
      is to highlight the types and functions of ultrasonic vocalizations emitted by
      laboratory rats and mice. Rats emit 3 types of ultrasonic vocalizations,
      depending on the animal's age, its environmental conditions, and its affective
      state. Rat pups emit a 40-kHz vocalization when they are separated from their
      mothers. Adult rats emit a 22-kHz vocalization in anticipation of inescapable
      aversive stimuli. These two types of vocalizations reflect a negative affective
      state of the animal. Rats produce a 50-kHz vocalization under nonaversive
      conditions, and these vocalizations reflect a positive affective state of the
      animal. Adult mice produce several different types of ultrasonic calls that can
      be classified as different syllables. Mice produce ultrasonic vocalizations
      during nonaggressive interactions, particularly during mating behaviors, but
      these vocalizations are not indicators of negative or positive affect. Therefore,
      the function of ultrasonic vocalizations in adult mice is likely only to
      facilitate or inhibit social interactions. Understanding the types and functions
      of ultrasonic vocalizations emitted by laboratory rodents may enable researchers
      and animal care personnel to use vocalizations as an indicator of an animal's
      behavior and affect.

PMID- 17203914
TI  - Extra-auditory effects of noise in laboratory animals: the relationship between
      noise and sleep.
AB  - Noise has both auditory and extra-auditory effects. Some of the most deleterious
      extra-auditory effects of noise are those leading to sleep disturbances. These
      disturbances seem to be related to both endogenous (physical parameters) and
      exogenous (sex, age) factors of noise. Despite correlative relations between
      noise level and awakenings, the scientific community has not reached consensus
      regarding a specific action of these factors on the different sleep stages. In
      animal research, 2 complementary main fields of research exist. One is focused on
      the positive modulation of sleep by repeated tone stimulation. The other concerns
      noise-related sleep disturbances. The few studies that have investigated noise
      related sleep disturbances suggest the following conclusions. First, sleep
      disturbances are greater upon exposure to environmental noise, whose frequency
      spectrum is characterized by high and ultrasonic sounds, than white noise.
      Second, unpredictability and pattern of noise events are responsible for
      extractions from both SWS and PS. Third, chronic exposure to noise permanently
      reduces and fragments sleep. Finally, in chronic noise exposure, an inter
      individual variability in SWS deficits is observed and correlated to a
      psychobiological profile related to an incapability to face stressful situations.
      Based on results from other research, acute noise-related sleep perturbations
      could result from an imbalance in the sleep-wake cycle in favor of arousing
      ascending systems. Chronic noise-related sleep disturbances may arise due to
      imbalance of the sleep-wake cycle and malfunctioning of the hypothalamo-pituitary
      adrenal axis which may both contribute to the development of pathology.

PMID- 17203915
TI  - Noise monitoring and establishment of a comprehensive hearing conservation
      program.
AB  - Here we discuss the importance of monitoring noise in contemporary animal
      facilities. Noise surveys and monitoring should be an integral part of an
      institution's Occupational Health and Safety Program. If noise levels equal or
      exceed 85 dB, then a Hearing Conservation Program must be initiated in accordance
      with Occupational Safety and Health Administration standards. The tenets of a
      comprehensive Hearing Conservation Program are outlined.

PMID- 17203916
TI  - Are investigators aware of environmental noise in animal facilities and that this
      noise may affect experimental data?
AB  - Control of environmental factors, such as noise, in animal facilities is
      important to ensure that research animals respond consistently to experimental
      procedures and that experimental results are not confounded by outside
      influences. A survey of personnel involved with animal facilities (173
      respondents) showed that almost all agreed with this statement. However, 48%
      thought that one or more environmental factors in their facilities could be
      stressing the animals, and a majority of respondents reported generation of
      audible noise from people (72% of respondents), fans (61%), and squeaky carts
      (56%). The presence of these noises was correlated with the perception of noise
      as a problem because of its psychologic and physiologic effects on the animals.
      The amount of time respondents spent in the facilities was strongly correlated
      with their perception of noise as a problem, with veterinarians spending the most
      time and perceiving the most problems, and professors and assistant/ associate
      professors spending the least and perceiving the fewest. Therefore, they may lack
      key knowledge that can affect their research goals. In addition, because faculty
      are the least aware of noise as a potential problem but are primarily responsible
      for designing experiments, research involving animals may be confounded by noise
      as an unknown variable. This effect may lead to unnecessary numbers of animals
      being required to achieve statistical significance and possibly to erroneous
      interpretation of results. On the basis of the findings of this survey, we
      present recommendations for improving the environment, particularly for
      decreasing the noise level, in animal facilities.

PMID- 17203917
TI  - Noise produced by vacuuming exceeds the hearing thresholds of C57Bl/6 and CD1
      mice.
AB  - Daily vacuuming of floors and flat-shelf racks is a standard procedure in our
      rodent housing rooms. To determine whether the noise produced by this activity is
      a potential stressor to animals used for transgenic and knockout mouse
      production, we measured the sound levels in our genetically engineered mouse
      facility under ambient conditions and at the in-cage and room levels during
      vacuuming. Spectral analysis showed that vacuuming produces a multitonal, low
      frequency noise that is not attenuated by microisolation caging with bedding
      material. Comparison of cage-level spectral analysis results with age-specific
      audiograms of C57Bl/6 and CD1 mice showed that vacuuming produces frequencies
      audible to C57Bl/6 mice at 3 and 6 mo of age and to CD1 mice at 1 mo of age.
      These findings suggest that vacuuming in animal rooms could be a source of stress
      to animals with these genetic backgrounds.

PMID- 17203918
TI  - Effect of noise on microvascular integrity in laboratory rats.
AB  - Housing rats in an environment with high personnel activity increases
      microvascular leakiness to albumin in the mesenteric microcirculation and causes
      mast cell degranulation. In this study, rats were exposed to daily 15-min
      episodes of 90-dB SPL noise to determine whether similar effects occurred and
      whether vitamin E with a-lipoic acid or Traumeel (a homeopathic anti-inflammatory
      analgesic) reduced these effects. Groups of rats fed a control diet (1000 IU/kg
      vitamin E) only, the control diet with Traumeel, or a diet with 10,000 IU/kg
      vitamin E and 1.65 g/kg lipoic acid were exposed to daily noise for 3 to 5 wk; a
      fourth group of rats, fed control diet, was housed with no excess noise. The rats
      were anesthetized, the superior mesenteric artery cannulated, and a portion of
      the microvasculature perfused for 1 min with fluoroscein isothiocyanate-albumin
      before fixing for microscopy. All groups exposed to excess noise had
      significantly more leaks per venule length and greater leak area per venule
      length than did the quiet group. However, the number and area of leaks in the
      rats that received Traumeel or vitamin E were significantly smaller than those in
      rats exposed to noise only. In addition, mast cell degranulation was
      significantly lower in rats given Traumeel. Thus exposure of rats to excessive
      noise produces structural damage in the mesenteric microvasculature that is
      significantly reduced by dietary supplements.

PMID- 17203919
TI  - Effects of two types and two genre of music on social behavior in captive
      chimpanzees (Pan troglodytes).
AB  - Is music just noise, and thus potentially harmful to laboratory animals, or can
      it have a beneficial effect? Research addressing this question has generated
      mixed results, perhaps because of the different types and styles of music used
      across various studies. The purpose of this study was to test the effects of 2
      different types (vocal versus instrumental) and 2 genres (classical vocal versus
      'easy-listening' vocal) of music on social behavior in 31 female and 26 male
      chimpanzees (Pan troglodytes). Results indicated that instrumental music was more
      effective at increasing affiliative behavior in both male and female chimpanzees,
      whereas vocal music was more effective at decreasing agonistic behavior. A
      comparison of 2 genre of vocal music indicated that easy-listening (slower tempo)
      vocal music was more effective at decreasing agonistic behavior in male
      chimpanzees than classical (faster tempo) vocal music. Agonistic behavior in
      females remained low (<0.5%) throughout the study and was unaffected by music.
      These results indicate that, like humans, captive chimpanzees react differently
      to various types and genres of music. The reactions varied depending on both the
      sex of the subject and the type of social behavior examined. Management programs
      should consider both type and genre when implementing a musical enrichment
      program for nonhuman primates.

PMID- 17203920
TI  - Misunderstandings, misperceptions, and mistakes.

PMID- 17203921
TI  - Fixed-dose, weight-adjusted, unfractionated heparin was as effective and safe as
      low-molecular-weight heparin for venous thromboembolism.

PMID- 17203922
TI  - Perioperative chemotherapy improved survival in resectable adenocarcinoma of the
      stomach or lower esophagus.

PMID- 17203923
TI  - 10-year follow-up showed benefit of adding radiotherapy to local excision for
      ductal carcinoma in situ.

PMID- 17203924
TI  - Anastrozole had a better risk-benefit profile than tamoxifen as adjuvant
      treatment for breast cancer in postmenopausal women.

PMID- 17203925
TI  - Review: adding cytotoxic drugs to a chemotherapy regimen increases tumor response
      rates and toxicity, but not survival in metastatic breast cancer.

PMID- 17203926
TI  - Review: erythropoietin or darbepoetin for anemia in patients with cancer produces
      both benefits and harms with no increase in survival.

PMID- 17203927
TI  - Atorvastatin reduced stroke and CV events after recent stroke or TIA in patients
      with no known coronary heart disease.

PMID- 17203928
TI  - Rosiglitazone reduced type 2 diabetes but increased heart failure in patients
      with impaired glycemic control.

PMID- 17203929
TI  - Periodic telephone counseling for polypharmacy improved compliance and reduced
      mortality.

PMID- 17203930
TI  - Ramipril did not reduce incident diabetes in patients with impaired glycemic
      control.

PMID- 17203931
TI  - Review: ACE inhibitors and angiotensin-receptor blockers reduce diabetes in
      hypertension and other CV risk factors.

PMID- 17203932
TI  - Review: nonselective nonsteroidal antiinflammatory drugs do not increase risk for
      cardiovascular events.

PMID- 17203933
TI  - Review: low-dose aspirin causes a small increase in gastrointestinal bleeding.

PMID- 17203934
TI  - Continuous venovenous hemodiafiltration increased survival more than did
      continuous hemofiltration in acute renal failure.

PMID- 17203935
TI  - Continuous venovenous hemodiafiltration and intermittent hemodialysis did not
      differ for improving survival in ARF with multiorgan dysfunction.

PMID- 17203936
TI  - Diuretics were superior to calcium-channel blockers and short-term ACE inhibitors
      for reducing heart failure in hypertension.

PMID- 17203937
TI  - Review: long-acting beta-agonists increase severe asthma exacerbations and asthma
      related deaths in children and adults.

PMID- 17203938
TI  - Review: long-acting beta2-adrenoceptor agonists are effective in poorly
      reversible chronic obstructive pulmonary disease.

PMID- 17203939
TI  - Review: anticholinergics, but not beta2-agonists, reduce exacerbations requiring
      hospitalization and respiratory deaths in COPD.

PMID- 17203940
TI  - No cardiac testing for intermediate-risk patients on beta-blockers was
      noninferior to testing before vascular surgery for preventing death and nonfatal
      MI.

PMID- 17203941
TI  - Review: opiate administration may alter physical examination findings, but does
      not increase management errors in acute abdominal pain.

PMID- 17203942
TI  - Review: history and physical examination can accurately identify migraine and the
      need for neuroimaging in patients with headache.

PMID- 17203943
TI  - Review: risk for cardiovascular events is increased with rofecoxib, diclofenac,
      and indomethacin but not celecoxib.

PMID- 17203944
TI  - Review: rofecoxib increases renal events and arrhythmia, but a COX-2-inhibitor
      class effect does not exist.

PMID- 17203945
TI  - Mitoproteome plasticity of rat brown adipocytes in response to cold acclimation.
AB  - Cold acclimation induces an adaptative increase in respiration in brown adipose
      tissue (BAT). A comparative analysis by two-dimensional differential in-gel
      electrophoresis of mitochondrial protein patterns found in rat control and cold
      acclimated BAT was performed. A total of 58 proteins exhibiting significant
      differences in their abundance was unambiguously identified. Proteins implicated
      in the major catabolic pathways were up-regulated as were ATP synthase and
      mitofilin. Moreover, these results support the fact that adipocytes can balance
      their ATP synthesis and their heat production linked to UCP1-sustained
      uncoupling.

PMID- 17203946
TI  - Immunoaffinity purification of plasma membrane with secondary antibody
      superparamagnetic beads for proteomic analysis.
AB  - Plasma membrane (PM) has very important roles in cell-cell interaction and signal
      transduction, and it has been extensively targeted for drug design. A major
      prerequisite for the analysis of PM proteome is the preparation of PM with high
      purity. Density gradient centrifugation has been commonly employed to isolate PM,
      but it often occurred with contamination of internal membrane. Here we describe a
      method for plasma membrane purification using second antibody superparamagnetic
      beads that combines subcellular fractionation and immunoisolation strategies.
      Four methods of immunoaffinity were compared, and the variation of crude plasma
      membrane (CPM), superparamagnetic beads, and antibodies was studied. The
      optimized method and the number of CPM, beads, and antibodies suitable for
      proteome analysis were obtained. The PM of mouse liver was enriched 3-fold in
      comparison with the density gradient centrifugation method, and contamination
      from mitochondria was reduced 2-fold. The PM protein bands were extracted and
      trypsin-digested, and the resulting peptides were resolved and characterized by
      MALDI-TOF-TOF and ESI-Q-TOF, respectively. Mascot software was used to analyze
      the data against IPI-mouse protein database. Nonredundant proteins (248) were
      identified, of which 67% are PM or PM-related proteins. No endoplasmic reticulum
      (ER) or nuclear proteins were identified according to the GO annotation in the
      optimized method. Our protocol represents a simple, economic, and reproducible
      tool for the proteomic characterization of liver plasma membrane.

PMID- 17203947
TI  - A new analytical material-enhanced laser desorption ionization (MELDI) based
      approach for the determination of low-mass serum constituents using fullerene
      derivatives for selective enrichment.
AB  - 60]fullerene derivatives (dioctadecyl methano[60]fullerene, [60]fullerenoacetic
      acid, and IDA-[60]fullerene) were prepared and subjected to a comprehensive
      characterization study including protein binding properties and capacity. These
      fullerene derivatives were successfully applied as material-enhanced laser
      desorption/ionization (MELDI) carrier materials. It is shown that diverse
      functionalities result in characteristic human serum peak patterns (m/z 2000-20
      000) in terms of signal intensity as well as the number of detectable masses. In
      addition, the fullerene derivatives clearly provided differences in the low
      molecular weight mass region (m/z 1000-4000) after elution of the adsorbed serum
      constituents, and [60]fullerenoacetic acid was the most effective carrier
      material. Novel high-speed, monolithic, high-resolution capillary columns,
      prepared by thermally initiated copolymerization of methylstyrene (MSt) and 1,2
      bis(p-vinylphenyl)ethane (BVPE) were employed for eluate separation and target
      spotting. Thus, serum compounds in the low-mass range were successfully
      fractionated and subjected to MALDI-MS/MS analysis. This contribution, hence,
      proposes a new "top-down" strategy for proteome research enabling protein
      profiling as well as biomarker identification in the low-mass range using
      selective enrichment, high-resolution separation, and offline MALDI-MS/MS
      evaluation.

PMID- 17203948
TI  - The influence of pharmacogenetics on fatty liver disease in the wistar and kyoto
      rats: a combined transcriptomic and metabonomic study.
AB  - Although fatty liver disease is caused by a number of toxicological insults and
      the metabolic syndrome, the exact mechanisms by which many of these
      pathophysiological stimulii induce fatty liver are unknown. The rapid and
      profound steatosis caused by orotic acid, resulting from an impairment in the
      production of ApoB, has been investigated in the Wistar strain rat using a
      combined transcriptomic and metabonomic/metabolomic approach. Analysis of liver
      tissue from rats exposed to orotic acid for 1, 3, and 14 days was performed by
      DNA microarrays and high resolution 1H NMR spectroscopy based metabonomics of
      both tissue extracts and intact tissue (n = 3). Data were analyzed using a
      combination of ANOVA and principal components analysis, used as a data reduction
      tool to visualize the most perturbed transcripts and metabolites. Orotic acid
      produced a profound 8-fold increase in total lipids, and in particular increases
      in resonances associated with polyunsaturated fats (CH=CH and CH2CH=CH groups).
      This was accompanied by increases in the concentrations of trimethylamine-oxide
      (TMAO), betaine, choline, and phosphocholine, as well as a relative decrease in
      glucose and glycogen. At the transcriptional level, perturbations were detected
      in both oxidative stress and osmoregulation/pH homeostasis. However, this
      contrasts with a previous transcriptomic/metabolic study of fatty liver disease
      in a combined data set of Wistar (out-bred) and Kyoto (in-bred) strains of rats,
      with only 4 transcripts being found to be in common between the two analyses.
      This emphasizes the need to understand how strain background interacts with a
      given toxic lesion or genetic modification.

PMID- 17203949
TI  - Proteomic analysis of the carbonate insoluble outer membrane fraction of the soft
      rot pathogen Dickeya dadantii (syn. Erwinia chrysanthemi) strain 3937.
AB  - We present results of the first comprehensive proteomic analysis of the outer
      membrane of the bacterial phytopathogen Dickeya dadantii strain 3937 and its
      response to virulence-contributing factors such as host plant extract, acidic
      stress, and iron starvation. We analyzed the carbonate-insoluble membrane
      fractions, which are highly enriched for outer membrane proteins, using two
      dimensional electrophoresis and identified the proteins by MALDI-TOF MS. Forty
      unique proteins were identified, some of which were differentially expressed
      under the above conditions.

PMID- 17203950
TI  - Functional proteome analysis of the banana plant (Musa spp.) using de novo
      sequence analysis of derivatized peptides.
AB  - We report the use of chemical derivatization with MALDI-MS/MS analysis for de
      novo sequence analysis. Using three frequently used homology-based search
      algorithms, we were able to identify more than 40 proteins from banana, a
      nonmodel plant with unsequenced genome. Furthermore, this approach allowed the
      identification of different isoforms. We also observed that the identification
      score obtained varied according to the position of the peptide sequences in the
      query using the MS-Blast algorithm.

PMID- 17203953
TI  - Relative quantification of proteins across the species boundary through the use
      of shared peptides.
AB  - We show that shared peptides of proteins that are encoded in different species
      are suitable for cross-species relative protein quantification. A 14N-containing
      proteome from the thermoacidophilic archaeon Sulfolobus tokodaii was mixed with a
      15N-labeled proteome from Sulfolobus solfataricus. Using three shared peptides
      per protein, the relative abundance of six orthologous proteins was calculated.
      Observed standard deviations were approximately 10%, indicating that the trypsin
      accessibility to cleavage sites was not altered in the orthologs. The abundance
      ratios of the and subunits of the Thermosome were 0.64 and 1.24 in Sulfolobus
      tokodaii compared to Sulfolobus solfataricus, suggesting a different
      stoichiometry of the complex in both species. In addition, an in silico study was
      performed on the occurrence of shared peptides. Inter- and intra-species peptide
      redundancy was investigated in the model organisms Homo sapiens, Mus musculus,
      Escherichia coli K12, Escherichia coli O157:H7, S. solfataricus, and S. tokodaii.
      M. musculus and H. sapiens share 30-50% of all peptides (6-15 residues).
      Moreover, approximately one-third of all proteins shared > or = 40% of their
      peptides with at least one other protein in the related species, thus offering
      strong potential for cross-species relative protein quantification. Conversely,
      approximately 40% of all peptides (6-15 residues) encoded in H. sapiens are
      encoded multiple times and therefore complicate identification and
      quantification.

PMID- 17203951
TI  - Histone H4 N-terminal acetylation in Kasumi-1 cells treated with depsipeptide
      determined by acetic acid-urea polyacrylamide gel electrophoresis, amino acid
      coded mass tagging, and mass spectrometry.
AB  - Disrupted patterns of acetylation and deacetylation of core histones play an
      important role in silencing transcription of hematopoietic important genes in
      acute myeloid leukemia (AML). A thorough investigation of these mechanisms and
      the response to pharmacologic modifiers will provide a better understanding of
      the role of histone acetylation in leukemogenesis. We describe here an analytical
      approach that combines acid urea polyacrylamide gel electrophoresis (AU-PAGE),
      amino acid coded mass tagging (AACM), and mass spectrometry (MS) for the
      investigation of histone acetylation patterns. The combined approach was used to
      follow the dynamics of H4 acetylation in Kasumi-1 cells harboring the fusion gene
      AML1/ETO shown to aberrantly recruit histone deacetylases (HDACs). The histones
      in Kasumi-1 cells were labeled by growing the cells in media in which lysine was
      replaced with stable isotope-labeled lysine (Lys-D4). Labeled and unlabeled cells
      were treated with depsipeptide and analyzed at different time points (0, 4, 8,
      12, 24, and 48 h). The cells were mixed, the histone was extracted, and
      acetylated H4 isoforms were separated using AU-PAGE before in-gel trypsin
      digestion. The digests were analyzed by MALDI-TOF MS. Peptides were identified by
      mass and isotope pattern. LC-MS/MS of Arg-C digests were also performed to verify
      the acetylation pattern for H4. The major pattern of acetylation was determined
      as follows: initial acetylation at K16, followed by acetylation at K12, and
      finally acetylation of either K8 and/or K5.

PMID- 17203952
TI  - Proteomic analysis of cervical-vaginal fluid: identification of novel biomarkers
      for detection of intra-amniotic infection.
AB  - Intra-amniotic infection (IAI) is associated with preterm birth and perinatal
      mortality. To identify potential biomarkers, we performed a comprehensive survey
      of the cervical-vaginal fluid (CVF) proteome from a primate IAI model utilizing
      multidimensional protein identification technology (LC/LC-MS/MS) and MALDI-TOF-MS
      analyses. Analyses of CVF proteome identified 205 unique proteins and
      differential expression of 27 proteins in controls and IAI samples. Protein
      expression signatures and immunodetection of specific biomarkers identified can
      be employed for noninvasive detection of IAI.

PMID- 17203954
TI  - Multidimensional chromatography: a powerful tool for the analysis of membrane
      proteins in mouse brain.
AB  - Understanding the function of membrane proteins is of fundamental importance due
      to their crucial roles in many cellular processes and their direct association
      with human disorders. However, their analysis poses a special challenge, largely
      due to their highly amphipathic nature. Until recently, analyses of proteomic
      samples mainly were performed by two-dimensional polyacrylamide gel
      electrophoresis (2D-PAGE), due to the unprecedented separation power of the
      technique. However, in conventional 2D-PAGE membrane proteins are generally
      underrepresented due to their tendency to precipitate during isoelectric focusing
      and their inefficient transfer from the first to the second dimension. As a
      consequence, several other separation techniques, primarily based on liquid
      chromatography (LC), have been employed for analysis of this group of proteins.
      In the present study, different LC-based methods were compared for the analysis
      of crude protein extracts. One- and two-dimensional high-performance liquid
      chromatographic (1D- and 2D-HPLC) separations of brain protein tryptic digests
      with a predicted concentration range of up to 5 orders of magnitude were found to
      be insufficient, thus making a preceding fractionation step necessary. An
      additional protein separation step was introduced and a 3D-PAGE-HPLC analysis was
      performed. The results of these experiments are compared with results of 2D
      PAGE/matrix-assisted laser desorption ionization mass spectrometric (MALDI MS)
      analyses of the same samples. Features, challenges, advantages, and disadvantages
      of the respective systems are discussed. The brain (mouse and human) was chosen
      as the analyzed tissue as it is of high interest in medical and pharmaceutical
      research into neurological diseases such as multiple sclerosis, stroke,
      Alzheimer's disease, and Parkinson's disease. The study is part of our ongoing
      research aimed at identifying new biomarkers for neurodegenerative diseases.

PMID- 17203955
TI  - De novo peptide sequencing and identification with precision mass spectrometry.
AB  - The recent proliferation of novel mass spectrometers such as Fourier transform,
      QTOF, and OrbiTrap marks a transition into the era of precision mass
      spectrometry, providing a 2 orders of magnitude boost to the mass resolution, as
      compared to low-precision ion-trap detectors. We investigate peptide de novo
      sequencing by precision mass spectrometry and explore some of the differences
      when compared to analysis of low-precision data. We demonstrate how the
      dramatically improved performance of de novo sequencing with precision mass
      spectrometry paves the way for novel approaches to peptide identification that
      are based on direct sequence lookups, rather than comparisons of spectra to a
      database. With the direct sequence lookup, it is not only possible to search a
      database very efficiently, but also to use the database in novel ways, such as
      searching for products of alternative splicing or products of fusion proteins in
      cancer. Our de novo sequencing software is available for download at
      http://peptide.ucsd.edu/.

PMID- 17203956
TI  - Improved collision-induced dissociation analysis of peptides by matrix-assisted
      laser desorption/ionization tandem time-of-flight mass spectrometry through 3
      sulfobenzoic acid succinimidyl ester labeling.
AB  - The sulfonation reagent, a succinimidyl ester of 3-sulfobenzoic acid, has been
      synthesized for effective peptide sequencing. It is capable of incorporating an
      additional mobile proton into the peptide backbone, thus, facilitating efficient
      collision-induced dissociation. This reagent is easily and inexpensively prepared
      in short time. Tandem mass spectra of the guanidinated and reagent-sulfonated
      peptides consist mainly of the y-ion series with higher intensities than those
      observed for solely guanidinated peptides. These enhanced tandem MS attributes
      significantly improved MASCOT total-ion scores, thus, allowing more confident
      peptide sequencing. This derivatization was also very effective for the analysis
      of tryptic digest of human blood serum proteins separated by two-dimensional gel
      electrophoresis. When used in LC-MALDI/MS/MS format, this type of derivatization
      does not adversely affect chromatographic efficiencies.

PMID- 17203957
TI  - A novel quantitative proteomics strategy to study phosphorylation-dependent
      peptide-protein interactions.
AB  - Phosphorylation-dependent protein-protein interactions provide the mechanism for
      a large number of intracellular signal transduction pathways. One of the goals of
      signal transduction research is to understand more precisely the nature of these
      phosphorylation-dependent interactions. Here, we report a novel strategy based on
      quantitative proteomics that allows for the rapid analysis of peptide-protein
      interactions with more than one phosphorylation site involved. The
      phosphorylation of two tyrosine residues, Y342 and Y346, within the linker B
      region of the protein-tyrosine kinase Syk is important for optimal signaling from
      the B cell receptor for antigen. We employed four amino-specific, isobaric
      reagents to differentially label proteins interacting in vitro with four Syk
      peptides containing none, one, or two phosphates on tyrosine residues Y342 and
      Y346, respectively. In total, 76 proteins were identified and quantified, 11 of
      which were dependent on the phosphorylation of individual tyrosine residues. One
      of the proteins, peroxiredoxin 1, preferably bound to phosphorylated Y346, which
      was further verified by Western blotting results. Thus, we demonstrate that the
      use of 4-fold multiplexing allows for relative protein measurements
      simultaneously for the identification of interacting proteins dependent on the
      phosphorylation of specific residues.

PMID- 17203958
TI  - 2-D DIGE analysis of liver and red blood cells provides further evidence for
      oxidative stress in schizophrenia.
AB  - The molecular disease mechanisms associated with schizophrenia remain largely
      unknown. Although primarily considered a disorder of the brain, there is evidence
      of a peripheral component to schizophrenia. In this study, we investigated liver
      tissue and red blood cells (RBC) from schizophrenia patients and controls using 2
      D DIGE proteomic analysis. Fourteen proteins were significantly altered in liver
      samples from schizophrenia patients (n = 15) compared to healthy controls (n =
      15). Analysis of the schizophrenia RBC proteome revealed 8 proteins significantly
      altered in samples from schizophrenia patients (13 antipsychotic-treated and 7
      drug-naive) compared to controls (n = 20). Six of the altered proteins in the
      liver and four of the altered RBC proteins are related to oxidative stress. These
      results corroborate our earlier findings obtained from post-mortem brain studies
      and substantiate our hypothesis that metabolic alterations leading to oxidative
      stress are linked to the schizophrenia disease process. Our results also suggest
      that at least some of the pathological processes associated with the
      schizophrenia disease process can be traced in peripheral tissue. If peripheral
      cells can be used as a disease surrogate, promising new investigative avenues
      could be explored.

PMID- 17203959
TI  - Comparative proteome analysis of serum from acute pulmonary embolism rat model
      for biomarker discovery.
AB  - Pulmonary embolism (PE) is a common, potentially fatal disease and its diagnosis
      is challenging because clinical signs and symptoms are nonspecific. In this
      study, to investigate protein alterations of a rat PE model, total serum proteins
      collected at different time points were separated by two-dimensional
      electrophoresis (2-DE) and identified using matrix assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).
      Bioinformatics analysis of 24 differentially expressed proteins showed that 20
      had corresponding protein candidates in the database. According to their
      properties and obvious alterations after PE, changes of serum concentrations of
      Hp, Fn, DBP, RBP, and TTR were selected to be reidentified by western blot
      analysis. Semiquantitative RT-PCR showed DBP, RBP, and TTR to be down-regulated
      at mRNA levels in livers but not in lung tissues. The low serum concentrations of
      DBP, RBP, and TTR resulted in the up-regulation of 25(OH)D3, vitamin A, and FT4
      (ligands of DBP, RBP, and TTR) after acute PE in rat models. The serum levels of
      Hp and Fn were detected in patients with DVT/PE and controls to explore their
      diagnostic prospects in acute PE because the mRNA levels of Hp and Fn were found
      to be up-regulated both in lung tissues and in livers after acute PE. Our data
      suggested that the concentration of serum Fn in controls was 79.42 +/- 31.57
      microg/L, whereas that of PE/DVT patients was 554.43 +/- 136.18 microg/L (P <
      0.001), and that the concentration of serum Hp in controls was 824.37 +/- 235.24
      mg/L, whereas that of PE/DVT patients was 2063.48 +/- 425.38 mg/L (P < 0.001).
      The experimental PE rat model selected in this study was more similar to the
      clinical process than the other existing PE animal models, and the findings
      indicated instant changes of serum proteins within 48 h after acute PE. The
      exploration of these differentially expressed proteins or their combination with
      existent markers such as D-dimer may greatly improve the accuracy of the
      diagnosis of acute PE, but diagnostic tests are still needed to evaluate the
      sensitivity and specificity of these markers and also the number of false
      positives and false negatives.

PMID- 17203960
TI  - Oxidized transthyretin in amniotic fluid as an early marker of preeclampsia.
AB  - Preeclampsia is a pregnancy-specific hypertensive syndrome and a major cause of
      maternal and fetal morbidity and mortality. At the present time, no reliable
      screening tests to identify women at risk are available. We have compared the
      amniotic fluids (AF) proteomic maps of five preeclamptic patients with those of
      five controls. The analysis was carried out by two-dimensional electrophoresis
      followed by peptide mapping and tandem mass spectrometric analysis. Besides the
      implementation of the previously published AF proteomic maps, our results show
      that transthyretin (TTR), the protein responsible for transporting both the
      thyroid hormone tyroxine and the retinol binding protein, is present in the AF of
      both preeclamptic and control women as a mixture of dimeric and post
      translationally modified monomeric forms. Although the nature of these forms is
      similar in both groups, the preeclamptic women showed a significant increase in
      the amount of monomeric proteins with respect to the control group. Since the TTR
      monomeric forms are the results of different oxidizing reactions, we hypothesize
      that the higher oxidative stress in preeclampsia is the major destabilizing
      factor of the TTR functional dimeric form in the preeclamptic women.

PMID- 17203961
TI  - Affibody molecules in protein capture microarrays: evaluation of multidomain
      ligands and different detection formats.
AB  - The importance of the ligand presentation format for the production of protein
      capture microarrays was evaluated using different Affibody molecules, produced
      either as single 6 kDa monomers or genetically linked head-to-tail multimers
      containing up to four domains. The performances in terms of selectivity and
      sensitivity of the monomeric and the multidomain Affibody molecules were compared
      by immobilization of the ligands on microarray slides, followed by incubation
      with fluorescent-labeled target protein. An increase in signal intensities for
      the multimers was demonstrated, with the most pronounced difference observed
      between monomers and dimers. A protein microarray containing six different
      dimeric Affibody ligands with specificity for IgA, IgE, IgG, TNF-alpha, insulin,
      or Taq DNA polymerase was characterized for direct detection of fluorescent
      labeled analytes. No cross-reactivity was observed and the limits of detection
      were 600 fM for IgA, 20 pM for IgE, 70 fM for IgG, 20 pM for TNF-alpha, 60 pM for
      insulin, and 10 pM for Taq DNA polymerase. Also, different sandwich formats for
      detection of unlabeled protein were evaluated and used for selective detection of
      IgA or TNF-alpha in human serum or plasma samples, respectively. Finally, the
      presence of IgA was determined using detection of directly Cy5-labeled normal or
      IgA-deficient serum samples.

PMID- 17203962
TI  - Different isoforms of apolipoprotein AI present heterologous post-translational
      expression in HIV infected patients.
AB  - Human immunodeficiency virus (HIV) is rapidly becoming a global health concern.
      Proteomics technology was employed to examine HIV infected plasma samples in an
      attempt to identify disease-associated proteins. By comparison with normal and
      HIV positive plasma samples, at least eight proteins were significantly changed
      in HIV infected plasma. In particular, apolipoprotein AI presents a heterogeneous
      change in expression level with different isoforms. Apolipoprotein AI could be a
      useful biomarker for HIV diagnosis.

PMID- 17203963
TI  - Genome-wide proteomics of Natronomonas pharaonis.
AB  - The aerobic, haloalkaliphilic archaeon Natronomonas pharaonis is able to survive
      in salt-saturated lakes of pH 11. According to genome analysis, the theoretical
      proteome consists of 2843 proteins. To reach further conclusions about its
      cellular physiology, the cytosolic protein inventory of Nmn. pharaonis has been
      analyzed using MS/MS on an ESI-Q-TOF mass spectrometer coupled on-line with a
      nanoLC system. The efficiency of this shotgun approach is illustrated by the
      identification of 929 proteins of which 886 are soluble proteins representing 41%
      of the cytosolic proteome. Cell lysis under denaturing conditions in water with
      subsequent separation by SDS-PAGE prior to nanoLC-MS/MS resulted in
      identification of 700 proteins. The same number (but a different subset) of
      proteins was identified upon cell lysis under native conditions followed by size
      fractionation (retaining protein complexes) prior to SDS-PAGE. Additional size
      fractionation reduced sample complexity and increased identification reliability.
      The set of identified proteins covers about 60% of the cytosolic proteins
      involved in metabolism and genetic information processing. Many of the identified
      proteins illustrate the high genetic variability among the halophilic archaea.

PMID- 17203964
TI  - Comparative urine analysis by liquid chromatography-mass spectrometry and
      multivariate statistics: method development, evaluation, and application to
      proteinuria.
AB  - We describe a platform for the comparative profiling of urine using reversed
      phase liquid chromatography-mass spectrometry (LC-MS) and multivariate
      statistical data analysis. Urinary compounds were separated by gradient elution
      and subsequently detected by electrospray Ion-Trap MS. The lower limit of
      detection (5.7-21 nmol/L), within-day (2.9-19%) and between-day (4.8-19%)
      analytical variation of peak areas, linearity (R2: 0.918-0.999), and standard
      deviation for retention time (<0.52 min) of the method were assessed by means of
      addition of seven 3-8 amino acid peptides (0-500 nmol/L). Relating the amount of
      injected urine to the area under the curve (AUC) of the chromatographic trace at
      214 nm better reduced the coefficient of variation (CV) of the AUC of the total
      ion chromatogram (CV = 10.1%) than relating it to creatinine (CV = 38.4%). LC-MS
      data were processed, and the common peak matrix was analyzed by principal
      component analysis (PCA) after supervised classification by the nearest shrunken
      centroid algorithm. The feasibility of the method to discriminate urine samples
      of differing compositions was evaluated by (i) addition of seven peptides at
      nanomolar concentrations to blank urine samples of different origin and (ii) a
      study of urine from kidney patients with and without proteinuria. (i) The added
      peptides were ranked as highly discriminatory peaks despite significant
      biological variation. (ii) Ninety-two peaks were selected best discriminating
      proteinuric from nonproteinuric samples, of which 6 were more intense in the
      majority of the proteinuric samples. Two of these 6 peaks were identified as
      albumin-derived peptides, which is in accordance with the early rise of albumin
      during glomerular proteinuria. Interestingly, other albumin-derived peptides were
      nondiscriminatory indicating preferential proteolysis at some cleavage sites.

PMID- 17203965
TI  - Characterisation of host defence proteins in milk using a proteomic approach.
AB  - Besides providing nutrition to the newborn, milk also protects the neonate and
      the mammary gland against infection. As well as the six major proteins, bovine
      milk contains minor proteins, not all of which have been characterized. In this
      study, we have subjected bovine skim milk, whey, and milk fat globule membrane
      (MFGM) fractions to both direct liquid chromatography-tandem mass spectrometry
      (LC-MS/MS), and two-dimensional electrophoresis (2-DE) followed by matrix
      assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry
      (MS) of individual protein spots to better characterize the repertoire of minor
      milk proteins, particularly those involved with host defense. Milk from peak
      lactation as well as during the period of colostrum formation and during mastitis
      were analyzed to gain a more complete sampling of the milk proteome. In total,
      2903 peptides were detected by LC-MS and 2770 protein spots by 2-DE. From these,
      95 distinct gene products were identified, comprising 53 identified through
      direct LC-MS/MS and 57 through 2-DE-MS. The latter were derived from a total of
      363 spots analyzed with 181 being successfully identified. At least 15 proteins
      were identified that are involved in host defense. These results demonstrate that
      the proteome of milk is more complex than has previously been reported and a
      significant fraction of minor milk proteins are involved in protection against
      infection.

PMID- 17203966
TI  - The oxidation of yeast alcohol dehydrogenase-1 by hydrogen peroxide in vitro.
AB  - Yeast alcohol dehydrogenase (YADH) plays an important role in the conversion of
      alcohols to aldehydes or ketones. YADH-1 is a zinc-containing protein, and it
      accounts for the major part of ADH activity in growing baker's yeast. To gain
      insight into how oxidative modification of the enzyme affects its function, we
      exposed YADH-1 to hydrogen peroxide in vitro and assessed the oxidized protein by
      LC-MS/MS analysis of proteolytic cleavage products of the protein and by
      measurements of enzymatic activity, zinc release, and thiol/thiolate loss. The
      results illustrated that Cys43 and Cys153, which reside at the active site of the
      protein, could be selectively oxidized to cysteine sulfinic acid (Cys-SO2H) and
      cysteine sulfonic acid (Cys-SO3H). In addition, H2O2 induced the formation of
      three disulfide bonds: Cys43-Cys153 in the catalytic domain, Cys103-Cys111 in the
      noncatalytic zinc center, and Cys276-Cys277. Therefore, our results support the
      notion that the oxidation of cysteine residues in the zinc-binding domain of
      proteins can go beyond the formation of disulfide bond(s); the formation of Cys
      SO2H and Cys-SO3H is also possible. Furthermore, most methionines could be
      oxidized to methionine sulfoxides. Quantitative measurement results revealed
      that, among all the cysteine residues, Cys43 was the most susceptible to H2O2
      oxidation, and the major oxidation products of this cysteine were Cys-SO2H and
      Cys-SO3H. The oxidation of Cys43 might be responsible for the inactivation of the
      enzyme upon H2O2 treatment.

PMID- 17203967
TI  - Protein markers of ischemic insult in brain endothelial cells identified using 2D
      gel electrophoresis and ICAT-based quantitative proteomics.
AB  - The blood-brain barrier (BBB) is formed by endothelial cells of cerebral
      microvessels sealed by tight junctions. Ischemic brain injury is known to
      initiate a series of biochemical and molecular processes that lead to the
      disruption of the BBB, development of vascular inflammation, and subsequent
      neurovascular remodeling including angiogenesis. Molecular effectors of these
      changes are multiple and are regulated in a dynamic fashion. The current study
      was designed to analyze changes in cellular and secreted proteins in rat brain
      endothelial cells (BEC) exposed to ischemic insult in vitro using two
      complementary quantitative proteomic approaches: two-dimensional gel
      electrophoresis (2DE) and isotope-coded affinity tag (ICAT)-based proteomics. We
      show a comprehensive qualitative and quantitative comparison between the two
      proteomic methods applied to the same experimental system with respect to their
      reproducibility, specificity, and the type of proteins identified. In total, >160
      proteins showed differential expression in response to the ischemic insult, with
      38 identified by 2DE and 138 by ICAT. Only 15 proteins were commonly identified.
      ICAT showed superior reproducibility over 2DE and was more suitable for detecting
      small, large, basic, hydrophobic, and secreted proteins than 2DE. However,
      positive identification of proteins by MS/MS was more reliably done using a 2DE
      based method compared to ICAT. Changes in proteins involved in nucleic acid,
      protein, and carbohydrate metabolism, signal transduction, cell structure,
      adhesion and motility, immunity and defense, cell cycle, and apoptosis were
      observed. The functional significance of observed protein changes was evaluated
      through a multifaceted protein classification and validation process, which
      included literature mining and comparative evaluation of protein changes in
      analogous in vitro and in vivo ischemia models. The comparative analyses of
      protein changes between the in vitro and in vivo models demonstrated a
      significant correlative relationship, emphasizing the 'translational' value of in
      vitro endothelial models in neurovascular research.

PMID- 17203968
TI  - Lysosomal membranes from beige mice contain higher than normal levels of
      endoplasmic reticulum proteins.
AB  - Chediak-Higashi syndrome is characterized by dysfunctional giant organelles of
      common origin, that is, lysosomes, melanosomes, and platelet dense bodies. Its
      defective gene LYST encodes a large molecular weight protein whose function is
      unknown. The Beige mouse also defective in Lyst is a good model of the human
      disease. Purified lysosomes from Beige and normal black mouse livers were used to
      carry out a proteomics study. Two-dimensional gel electrophoretic separation of
      soluble lysosomal proteins of Beige and normal mice revealed no major
      differences. The cleavable isotope-coded affinity tag (cICAT) technique was used
      to compare the composition of Beige and normal lysosomal membrane proteins. While
      the levels of common proteins, that is, Lamp1, Lamp2, and Niemann-Pick type C1,
      were decreased in Beige mice, there was an increase in the levels of endoplasmic
      reticulum (ER) resident proteins, for example, cytochrome P450, NADPH-cytochrome
      P450 oxidoreductase, and flavin-containing monooxygenase. Confocal microscopy
      confirmed that another ER protein, calnexin, colocalizes with Lamp1 on membranes
      of giant lysosomes from fibroblasts of Chediak-Higashi syndrome patient. Our
      results suggest that LYST may play a role in either preventing inappropriate
      incorporation of proteins into the lysosomal membrane or in membrane
      recycling/maturation.

PMID- 17203969
TI  - Protein phosphorylation and expression profiling by Yin-yang multidimensional
      liquid chromatography (Yin-yang MDLC) mass spectrometry.
AB  - A system which consisted of multidimensional liquid chromatography (Yin-yang
      MDLC) coupled with mass spectrometry was used for the identification of peptides
      and phosphopeptides. The multidimensional liquid chromatography combines the
      strong-cation exchange (SCX), strong-anion exchange (SAX), and reverse-phase
      methods for the separation. Protein digests were first loaded on an SCX column.
      The flow-through peptides from SCX were collected and further loaded on an SAX
      column. Both columns were eluted by offline pH steps, and the collected fractions
      were identified by reverse-phase liquid chromatography tandem mass spectrometry.
      Comprehensive peptide identification was achieved by the Yin-yang MDLC-MS/MS for
      a 1 mg mouse liver. In total, 14 105 unique peptides were identified with high
      confidence, including 13 256 unmodified peptides and 849 phosphopeptides with 809
      phosphorylated sites. The SCX and SAX in the Yin-Yang system displayed
      complementary features of binding and separation for peptides. When coupled with
      reverse-phase liquid chromatography mass spectrometry, the SAX-based method can
      detect more extremely acidic (pI < 4.0) and phosphorylated peptides, while the
      SCX-based method detects more relatively basic peptides (pI > 4.0). In total, 134
      groups of phosphorylated peptide isoforms were obtained, with common peptide
      sequences but different phosphorylated states. This unbiased profiling of protein
      expression and phosphorylation provides a powerful approach to probe protein
      dynamics, without using any prefractionation and chemical derivation.

PMID- 17203970
TI  - Proteome profile of cytosolic component of zebrafish liver generated by LC-ESI
      MS/MS combined with trypsin digestion and microwave-assisted acid hydrolysis.
AB  - The zebrafish genome has recently been sequenced and annotated allowing for high
      throughput proteomic analysis. Here, we report for the first time a proteomic
      subset of zebrafish liver, an important organ for metabolizing toxins. Using a
      newly developed analytical procedure, we have identified 1204 proteins from the
      cytosolic component of a zebrafish liver tissue sample. Our methods involve cell
      compartment fractionation of liver tissue samples, four levels of protein
      digestion, and off-line two-dimensional liquid chromatography (2-D LC)
      separations of resultant peptides. Proteins are identified using an electrospray
      ionization quadrupole time-of-flight tandem mass spectrometer (ESI-QTOF MS/MS),
      which provides high-resolution and high-accuracy mass measurement of peptide ions
      and their fragment ions. We demonstrate that greater proteome coverage can be
      achieved by combining the results obtained from four methods of protein
      digestion: three tryptic digests (one in buffer, one in methanol, and another in
      SDS), and a microwave-assisted acid hydrolysate of the protein extracts.
      Identified proteins--which included several groups of established protein
      biomarkers--were functionally classified. We discuss the functions and
      implications of these biomarkers within the context of zebrafish toxicology.

PMID- 17203971
TI  - Protein expression profiles in the epidermis of cyclooxygenase-2 transgenic mice
      by 2-dimensional gel electrophoresis and mass spectrometry.
AB  - Exposure of murine skin to tumor-promoting agents such as 12-O-tetradecanoyl
      phorbol-13-acetate (TPA) causes up-regulation of cyclooxygenase-2 (COX-2) and
      increased prostaglandin (PG) synthesis. Pharmacological inhibition of COX-2
      significantly reduces skin tumor development. However, we previously demonstrated
      that K14.COX-2 transgenic (TG) mice that overexpressed COX-2 in the epidermis
      were unexpectedly resistant to tumor development under the classical 7,12
      dimethylbenz[a]anthracene-TPA protocol. In the present study, we employed a
      proteomic approach of 2-dimensional gel electrophoresis (2-DE) and mass
      spectrometry to profile differentially expressed proteins in the epidermis of
      K14.COX-2 TG and wild-type control mice. Various 2-DE approaches were used to
      identify the maximum number of differentially expressed proteins: 20 for
      untreated samples, 3 for acetone-treated samples, and 22 for TPA-treated samples.
      These proteins include 14-3-3 sigma, numerous actin fragments, actin filament
      related proteins cofilin-1 and destrin, galectin-3, galectin-7, prohibitin,
      S100A6, S100A9, and many others. The differential expression of galectin-3,
      galectin-7, S100A9 was validated by Western blot analysis and/or
      immunohistochemical analysis. The current data suggest that some of the
      differentially expressed proteins might increase apoptosis and cell cycle arrest,
      which, in turn, may provide insight into the role of COX-2 in skin tumorigenesis.

PMID- 17203972
TI  - Interactome of transforming growth factor-beta type I receptor (TbetaRI):
      inhibition of TGFbeta signaling by Epac1.
AB  - Transforming growth factor-beta (TGFbeta) is a potent regulator of cell growth,
      differentiation, and apoptosis. Type I TGFbeta receptor (TbetaRI) is the key
      receptor for initiation of intracellular signaling by TGFbeta. Here we report
      proteomics-based identification of proteins that form a complex with TbetaRI.
      Using 2D-GE and MALDI TOF mass spectrometry, we identified 16 proteins that
      specifically interacted with a GST-fused TbetaRI Thr204Asp construct with
      constitutively active serine/threonine kinase. We confirmed interactions of the
      receptor with cAMP regulated guanine nucleotide exchange factor 1 (Epac1), beta
      spectrin, PIASy, and beta-catenin proteins using immunoblotting. Interaction of
      the receptor with Epac1 required intact kinase activity of TbetaRI but was not
      affected by deletion of cAMP-binding domain of Epac1. TGFbeta1-induced C-terminal
      phosphorylation of Smad2 was inhibited in vivo and in vitro in the presence of
      Epac1. Epac1 inhibited also TGFbeta1/TbetaRI-dependent transcriptional
      activation, as evaluated by luciferase reporter assays. We observed that
      expression of Epac1 counteracted TGFbeta/TbetaRI-dependent decrease of cell
      adhesion and TGFbeta/TbetaRI-induced stimulation of cell migration. Thus, we have
      reported novel TRI-interacting proteins and have shown that Epac1 inhibited
      TGFbeta-dependent regulation of cell migration and adhesion.

PMID- 17203973
TI  - The proteomic reactor facilitates the analysis of affinity-purified proteins by
      mass spectrometry: application for identifying ubiquitinated proteins in human
      cells.
AB  - Mass spectrometry (MS) coupled to affinity purification is a powerful approach
      for identifying protein-protein interactions and for mapping post-translational
      modifications. Prior to MS analysis, affinity-purified proteins are typically
      separated by gel electrophoresis, visualized with a protein stain, excised, and
      subjected to in-gel digestion. An inherent limitation of this series of steps is
      the loss of protein sample that occurs during gel processing. Although methods
      employing in-solution digestion have been reported, they generally suffer from
      poor reaction kinetics. In the present study, we demonstrate an application of a
      microfluidic processing device, termed the Proteomic Reactor, for enzymatic
      digestion of affinity-purified proteins for liquid chromatography tandem mass
      spectrometry (LC-MS/MS) analysis. Use of the Proteomic Reactor enabled the
      identification of numerous ubiquitinated proteins in a human cell line expressing
      reduced amounts of the ubiquitin-dependent chaperone, valosin-containing protein
      (VCP). The Proteomic Reactor is a novel technology that facilitates the analysis
      of affinity-purified proteins and has the potential to aid future biological
      studies.

PMID- 17203974
TI  - Identification of specific protein markers in microdissected hepatocellular
      carcinoma.
AB  - At present, the molecular mechanisms of hepatocellular carcinogenesis are not
      well-understood, and hepatocellular carcinoma (HCC) stays one of the most
      frequent and high-risk metastatic visceral neoplasms worldwide. For the
      identification of tumor-relevant proteins, we analyzed microdissected cells from
      nontumorous liver tissue (n = 28) and tissue derived from hepatic tumor center (n
      = 25), as well as tumor margin (n = 23). We unequivocally identified 53 proteins
      from hepatic tumor tissues by peptide fingerprint mapping and SELDI mass
      spectrometry that were separated using two-dimensional gel electrophoresis. Among
      a number of signals that were detected as significantly different in the protein
      profiling analysis, we identified for the first time ferritin light subunit (FLS)
      and adenylate kinase 3 alpha-like 1 (AK3), showing decreased expressions in
      hepatic tumor, as well as biliverdin reductase B (BVRB) that was upregulated in
      HCC. The use of ProteinChip technology in combination with tissue microdissection
      gives insight of the complex changes occurring at the protein level in
      hepatocellular cancer associated with tumor development and progression and
      resulted in three new potential diagnostically useful markers.

PMID- 17203975
TI  - Rapid enrichment of phosphopeptides and phosphoproteins from complex samples
      using magnetic particles coated with alumina as the concentrating probes for
      MALDI MS analysis.
AB  - In this study, we used nanocomposite magnetic particles coated with alumina as
      the affinity probes to selectively concentrate phosphorylated peptides and
      proteins from a low volume of sample solution. Tryptic digest products of
      phosphoproteins including alpha and beta-caseins, human protein phosphatase
      inhibitor 1, nonfat milk, egg white, and a cell lysate were used as the samples
      to demonstrate the feasibility of this approach. In only 30 and 90 s,
      phosphopeptides and phosphoproteins sufficient for characterization by MALDI-MS
      were enriched by the particles, respectively. Proteins trapped on the particles
      could be directly digested on the particles. The same particles in the digest
      solution were employed for enrichment of phosphopeptides. We estimated the
      required time for performing the enrichment of phosphopeptides from complex
      samples and characterization by MALDI MS was within 5 min. A small volume (50
      microL) and a low concentration (5 x 10(-10) M) of tryptic digest product of a
      phosphoprotein sample could be dramatically enriched and characterized using this
      approach.

PMID- 17203976
TI  - Snake venomics of Bitis gabonica gabonica. Protein family composition, subunit
      organization of venom toxins, and characterization of dimeric disintegrins
      bitisgabonin-1 and bitisgabonin-2.
AB  - The protein composition of the venom of the East African Gaboon viper (Bitis
      gabonica gabonica) was analyzed using RP-HPLC, N-terminal sequencing, MALDI-TOF
      peptide mass fingerprinting, and CID-MS/MS. In total, 35 proteins of molecular
      masses in the range of 7-160 kDa and belonging to 12 toxin families were
      identified. The most abundant proteins were serine proteinases (26.4%), Zn2+
      metalloproteinases (22.9%), C-type lectin-like proteins (14.3%), PLA2s (11.4%),
      and bitiscystatin (9.8%). Other protein classes, that is, bradykinin-potentiating
      peptides, dimeric disintegrins, Kunitz-type inhibitor, DC-fragments, sv-VEGF,
      CRISP, and L-amino acid oxidase, comprised between 1.3 and 3.4% of the total
      venom proteome. Only 11 venom-secreted proteins matched any of the previously
      reported 22 partial or full-length venom gland transcripts. In addition, venome
      and transcriptome depart in their relative abundances of different toxin
      families. The proteomic characterization of purified B. gabonica gabonica
      proteins run under nonreducing and reducing SDS-PAGE conditions revealed their
      aggregation state and subunit composition. Multimeric proteins included
      heterodimeric disintegrins, homodimeric sv-VEGF-A, heterodimeric (alphabeta) and
      tetrameric (alphabeta)4 C-type lectins, and multimeric PIII Zn2+
      metalloproteinases. Determination of the complete primary structure and subunit
      composition of the two major dimeric disintegrins, bitisgabonin-1 and
      bitisgabonin-2, showed that each comprised a distinct RGD- and MLD-bearing
      subunit and a common, N-terminal-blocked, RGD-containing subunit identical to the
      disintegrin domain of the PII Zn2+-metalloproteinase 4. Cell adhesion inhibition
      assays showed that bitisgabonin-1 (RGD-RGD) is a potent inhibitor of integrin
      alpha5beta1, whereas bitisgabonin-2 (MLD-RGD) is a better antagonist of integrins
      alpha4beta1 and alpha9beta1.

PMID- 17203977
TI  - A top-down/bottom-up study of the ribosomal proteins of Caulobacter crescentus.
AB  - Ribosomes from the Gram-negative alpha-proteobacterium Caulobacter crescentus
      were isolated using standard methods. Proteins were separated using a two
      dimensional liquid chromatographic system that allowed the analysis of whole
      proteins by direct coupling to an ESI-QTOF mass spectrometer and of proteolytic
      digests by a number of mass spectrometric methods. The masses of 53 of 54
      ribosomal proteins were directly measured. Protein identifications and proposed
      post-translational modifications were supported by proteolysis with trypsin,
      endoprotease Glu-C, and exoproteases carboxypeptidases Y and P. Tryptic peptide
      mass maps show an average sequence coverage of 62%, and carboxypeptidase C
      terminal sequence tagging provided unambiguous identification of the small,
      highly basic proteins of the large subunit. C. crescentus presents some post
      translational modifications that are similar to those of Escherichia coli (e.g.,
      N-terminal acetylation of S9 and S18) along with some unique variations, such as
      a near absence of L7 and extensive modification of L11. The comprehensive
      description of this organism's ribosomal proteome provides a foundation for the
      study of ribosome structure, dependence of post-translational modifications on
      growth conditions, and the evolution of subcellular organelles.

PMID- 17203979
TI  - Assessment of hierarchical clustering methodologies for proteomic data mining.
AB  - Hierarchical clustering methodology is a powerful data mining approach for a
      first exploration of proteomic data. It enables samples or proteins to be grouped
      blindly according to their expression profiles. Nevertheless, the clustering
      results depend on parameters such as data preprocessing, between-profile
      similarity measurement, and the dendrogram construction procedure. We assessed
      several clustering strategies by calculating the F-measure, a widely used quality
      metric. The combination, on logged matrix, of Pearson correlation and Ward's
      methods for data aggregation is among the best clustering strategies, at least
      with the data sets we studied. This study was carried out using PermutMatrix, a
      freely available software derived from transcriptomics.

PMID- 17203978
TI  - Protein expression in a Drosophila model of Parkinson's disease.
AB  - Liquid chromatographies coupled to mass spectrometry and database analysis
      techniques are used to carry out a large-scale proteome characterization for a
      Drosophila model of Parkinson's disease. Semiquantitative analysis is performed
      on A30P alpha-synuclein expressing transgenic Drosophila and a control lacking
      the gene at presymptomatic, early, and advanced disease stages. Changes in gene
      expression at the level of the proteome are compared with changes reported from
      published transcriptome measurements. A summary of the comparison indicates that
      approximately 44% of transcripts that show changes can also be observed as
      proteins. However, the patterns of change in protein expression vary
      substantially compared with the patterns of change observed for corresponding
      transcripts. In addition, the expression changes of many genes are observed for
      only transcripts or proteins. Proteome measurements provide evidence for
      dysregulation of a group of proteins associated with the actin cytoskeleton and
      mitochondrion at presymptomatic and early disease stages that may presage the
      development of later symptoms. Overall, the proteome measurements provide a view
      of gene expression that is highly complementary to the insights obtained from the
      transcriptome.

PMID- 17203980
TI  - Comparative proteomic analysis of chronic myelogenous leukemia cells: inside the
      mechanism of imatinib resistance.
AB  - Imatinib is the first molecular targeted therapy that has shown clinical success,
      but imatinib acquired resistance, although a rare event, is critical during the
      therapy of chronic myelogenous leukaemia (CML). With the aim of better
      understanding the molecular mechanisms accompanying acquisition of resistance to
      this drug, a comparative proteomic approach was undertaken on CML cell lines LAMA
      84 S (imatinib sensitive) and LAMA 84 R (imatinib resistant). Forty-four
      differentially expressed proteins were identified and categorized into five main
      functional classes: (I) heat shock proteins and chaperones; (II) nucleic acid
      interacting proteins (binding/synthesis/stability); (III) structural proteins,
      (IV) cell signaling, and (V) metabolic enzymes. Several heat shock proteins known
      to complex Bcr-Abl were overexpressed in imatinib resistant cells, showing a
      possible involvement of these proteins in the mechanism of resistance. HnRNPs
      also resulted in being up-regulated in imatinib resistant cells. These proteins
      have been shown to be strongly and directly related to Bcr-Abl activity. To our
      knowledge, this is the first direct proteomic comparison of imatinib
      sensitive/resistant CML cell lines.

PMID- 17203981
TI  - Identification and dynamics of proteins adhering to the surface of medical
      silicones in vivo and in vitro.
AB  - Silicone has been used in medical practice as a paradigmatic implant material for
      decades despite significant detrimental side effects. Our targeted proteomics
      approach was aimed at identification of the proteins adsorbed to the surface of
      silicone because they have been characterized as key components in the onset and
      perpetuation of local immune reactions to silicone. The composition of the
      proteinacious film, the dynamics of protein deposition, and protein modifications
      after adsorption were analyzed both in vivo and in vitro. Differential analysis
      of protein deposition was performed, followed by protein identification with mass
      spectrometry, database matching, and Western blots. Thus far, we have identified
      the 30 most abundant proteins deposited on the surface of silicone, the largest
      known inventory of such proteins so far. Structural and extracellular matrix
      proteins predominated, followed by mediators of host defense, metabolism,
      transport, and stress related proteins. In addition, several biochemical
      modifications of fibronectin, vitronectin, and heat shock protein 60 were
      detected. Our analyses also revealed previously undetected proteins deposited on
      the surface of silicone. As tentative initiators and/or modulators of the
      response to silicone, they are therefore valuable candidates for prognosis and
      therapy.

PMID- 17203982
TI  - Mass spectrometric identification of serum peptides employing derivatized
      poly(glycidyl methacrylate/divinyl benzene) particles and mu-HPLC.
AB  - Biomarkers play a key role in preclinical screening and diagnosis of a disease.
      Various support materials are utilized for this task, in combination with MALDI
      TOF-MS. The way to effectively bind serum contents and their profiling is well
      elaborated by the material-enhanced laser desorption ionization (MELDI) approach.
      In this particular work, focus is placed on the development of a strategy to
      identify low molecular weight serum peptides. Poly(GMA/DVB) is derivatized in a
      way to achieve an affinity termed as immobilized metal ion affinity
      chromatography (IMAC). Iminodiacetic acid (IDA) is used as a chelating ligand,
      whereas copper (Cu2+) acts as a metal ion for complexing peptides and proteins
      out of blood serum. Polymer binds the serum compounds over a broad mass range,
      which includes low mass peptides and high mass albumin (66 kDa). Bound contents
      are eluted from material by an acetonitrile/trifluoroacetic acid mixture, which
      proves the reversible nature of metal and amino acid linkage. Polystyrene/divinyl
      benzene (PS/DVB) monolithic capillary column is used for fractionation through RP
      HPLC, prior to the target spotting. The tandem TOF fragment ion mass spectra of
      each fraction is acquired and used to search against the Swiss-Prot database,
      using the Mascot search engine for the identification of peptides.

PMID- 17203983
TI  - Microwave-enhanced ink staining for fast and sensitive protein quantification in
      proteomic studies.
AB  - A novel microwave-enhanced ink staining method was developed for rapid and
      sensitive estimation of protein content in sample buffers containing chaotropes,
      dyes, detergents, and reducing agents. Dye-based Blue-Black ink was used to
      quantitatively visualize proteins spotted on a nitrocellulose membrane. The total
      staining time was greatly reduced to 3 min by brief exposure to microwave
      radiation. The stained membrane was washed with distilled water, baked in a
      microwave oven for complete desiccation, transparentized with mineral oil, and
      documented by a desktop scanner or densitometer. Only 1 microL of protein sample
      (protein solubilized in SDS-PAGE sample buffer or IEF rehydration buffer) was
      used for protein spotting. The novel solid-phase protein assay gives a 500-fold
      dynamic range from 19.5 to 10000 ng/microL and can be scaled up for high
      throughput protein quantification analysis. The fast, sensitive and low-cost
      microwave-enhanced ink staining procedure is ideal for protein quantification in
      proteomic analysis.

PMID- 17203984
TI  - Prediction of error associated with false-positive rate determination for peptide
      identification in large-scale proteomics experiments using a combined reverse and
      forward peptide sequence database strategy.
AB  - In recent years, a variety of approaches have been developed using decoy
      databases to empirically assess the error associated with peptide identifications
      from large-scale proteomics experiments. We have developed an approach for
      calculating the expected uncertainty associated with false-positive rate
      determination using concatenated reverse and forward protein sequence databases.
      After explaining the theoretical basis of our model, we compare predicted error
      with the results of experiments characterizing a series of mixtures containing
      known proteins. In general, results from characterization of known proteins show
      good agreement with our predictions. Finally, we consider how these approaches
      may be applied to more complicated data sets, as when peptides are separated by
      charge state prior to false-positive determination.

PMID- 17203985
TI  - Prediction of missed cleavage sites in tryptic peptides aids protein
      identification in proteomics.
AB  - Protein identification via peptide mass fingerprinting (PMF) remains a key
      component of high-throughput proteomics experiments in post-genomic science.
      Candidate protein identifications are made using bioinformatic tools from peptide
      peak lists obtained via mass spectrometry (MS). These algorithms rely on several
      search parameters, including the number of potential uncut peptide bonds matching
      the primary specificity of the hydrolytic enzyme used in the experiment.
      Typically, up to one of these "missed cleavages" are considered by the
      bioinformatics search tools, usually after digestion of the in silico proteome by
      trypsin. Using two distinct, nonredundant datasets of peptides identified via PMF
      and tandem MS, a simple predictive method based on information theory is
      presented which is able to identify experimentally defined missed cleavages with
      up to 90% accuracy from amino acid sequence alone. Using this simple protocol, we
      are able to "mask" candidate protein databases so that confident missed cleavage
      sites need not be considered for in silico digestion. We show that that this
      leads to an improvement in database searching, with two different search engines,
      using the PMF dataset as a test set. In addition, the improved approach is also
      demonstrated on an independent PMF data set of known proteins that also has
      corresponding high-quality tandem MS data, validating the protein
      identifications. This approach has wider applicability for proteomics database
      searching, and the program for predicting missed cleavages and masking Fasta
      formatted protein sequence databases has been made available via http://
      ispider.smith.man.ac uk/MissedCleave.

PMID- 17203986
TI  - Anticoagulant agents are mainstay therapies in the prevention and treatment of
      arterial and venous thrombosis. Introduction.

PMID- 17203987
TI  - Burden of disease: medical and economic impact of acute coronary syndromes.
AB  - Despite advances in treatment, acute coronary syndromes (ACS), which consist
      mainly of ST-segment elevation myocardial infarction (STEMI) and unstable angina
      (UA)/non-STEMI (NSTEMI), present an enormous medical, social, and economic burden
      worldwide. According to public databases, 879 000 patients were discharged from
      US hospitals with a diagnosis of ACS in 2003. Globally, ACS in the form of
      myocardial infarction are responsible for almost half of all deaths related to
      cardiovascular disease. One third of STEMI patients die within 24 hours of onset,
      and about 15% of UA/NSTEMI patients will die or experience reinfarction within 30
      days. ACS also exact a high toll in terms of treatment-related and indirect
      economic costs. Direct medical costs of ACS are estimated at $75 billion, with a
      significant portion going toward drug therapy and associated costs. Data from
      clinical trials indicate that a management strategy including antithrombotic
      therapy can reduce ACS-related morbidity and mortality and related costs. More
      recently developed antithrombotic agents may have clinical and economic
      advantages over older therapies.

PMID- 17203988
TI  - New treatment options for acute coronary syndromes.
AB  - Complications from atherosclerotic coronary artery disease are the principal
      cause of death worldwide. Many therapeutic strategies have been developed to
      reduce the burden of this disease. Systemic antithrombotic therapy, typically
      with unfractionated heparin, has long been a mainstay in the management of acute
      coronary syndromes (ACS) despite several limitations, including intravenous
      administration and unpredictable pharmacokinetics necessitating frequent
      monitoring. In recent years, newer agents without these limitations have been
      developed and evaluated in clinical trials. This review focuses on novel
      antithrombotic therapies for ACS, particularly fondaparinux sodium, a synthetic
      inhibitor of clotting factor Xa.

PMID- 17203989
TI  - Easing the economic burden of acute coronary syndromes: cost-effectiveness of
      emerging therapies.
AB  - Although only part of the entire treatment regimen, antithrombotic therapy
      represents a large portion of the total costs associated with acute coronary
      syndromes (ACS) treatment. Unfractionated heparin (UFH), the mainstay of
      antithrombotic therapy, carries the risk of bleeding and associated
      interventions, and must be closely monitored. UFH therapy also has an increased
      risk of heparin-induced thrombocytopenia (HIT) and osteoporosis. These drawbacks
      prompted the development of newer antithrombotic agents, particularly low
      molecular weight heparins (LMWH) and factor Xa inhibitors. LMWH have several
      clinical advantages over UFH and has been demonstrated to be more effective than
      UFH in ACS. Because UFH is inexpensive, newer therapies need to demonstrate
      economic attractiveness over UFH. In addition to acquisition costs, it is
      important to consider the cost of all key components throughout the continuum of
      care. Health economic analyses show that the clinical advantages of the LMWH
      enoxaparin are also likely to result in net cost-saving benefits, due to
      reductions in diagnostic catheterization, percutaneous transluminal coronary
      angioplasty, and intensive care unit length of stay. Fondaparinux, an indirect
      inhibitor of factor Xa, does not require routine monitoring or multiple daily
      dosing, and is unlikely to interact with HIT antibodies. Large randomized
      clinical trials have shown that fondaparinux is at least as safe and efficacious
      as enoxaparin or UFH in the prevention of venous thromboembolism (VTE) and
      treatment of deep vein thrombosis or pulmonary embolism. Data from 2 recently
      published trials are similarly indicating noninferiority of fondaparinux in ACS
      patients. Health economic analysis of fondaparinux treatment is currently limited
      to VTE scenarios but point to a cost benefit associated with fondaparinux
      compared with enoxaparin.

PMID- 17203990
TI  - Human papillomavirus and cervical cancer: burden of illness and basis for
      prevention.
AB  - Genital infection with human papillomaviruses (HPV) is one of the most common
      sexually transmitted conditions. The central causal role in cervical
      carcinogenesis of the so-called high oncogenic-risk (HR)-HPV genotypes, such as
      HPV-16, has been established as a likely but not sufficient cause of virtually
      all cases of cervical cancer worldwide. HR-HPV infection also causes a
      substantial proportion of other anogenital neoplasms and oral squamous cell
      carcinomas. Infection with low-oncogenic-risk HPV, such as HPV-6 and -11, causes
      a large proportion of low-grade squamous intraepithelial lesions of the cervix
      and benign lesions of the anogenital areas known as condylomata acuminata
      (genital warts). Subclinical and clinical HPV infections are responsible for high
      morbidity and impose a great burden on the healthcare system. Organized or
      opportunistic screening with Papanicolaou (Pap) cytology in high-income countries
      has substantially reduced cervical cancer morbidity and mortality during the last
      50 years. However, Pap cytology screening has failed to reduce cervical cancer
      mortality in many middle-income countries, and most low-income countries cannot
      make the necessary public health investments to deploy organized screening. The
      availability of 2 prophylactic HPV vaccines represents the best hope for
      preventing most cases of cervical cancer and HPV-associated diseases.

PMID- 17203991
TI  - Decreasing risk: impact of HPV vaccination on outcomes.
AB  - Cervical cancer, caused by oncogenic types of human papillomavirus (HPV), remains
      a major health problem worldwide. The recent introduction of a quadrivalent
      vaccine (Gardasil), which targets HPV strains responsible for approximately 70%
      of cervical cancer cases and 90% of genital warts, has ushered in new hope of
      substantially reducing global prevalence of HPV disease. A further bivalent HPV
      vaccine (Cervarix) is in the offing. However, many issues still need to be
      addressed, including actual vaccine efficacy in preventing cervical cancer,
      public acceptance, use of the vaccine in men, vaccine access, costs, and impact
      of the vaccine on cervical cancer screening programs. This review analyzes some
      of these issues, and emphasizes the need for a coordinated effort of patients,
      parents, health professionals, hospitals, and policymakers to ensure successful
      implementation of vaccination programs in the United States.

PMID- 17203992
TI  - Overcoming barriers to adherence to HPV vaccination recommendations.
AB  - Human papillomavirus (HPV) is a critical factor in the development of cervical
      cancer and can lead to genital warts and other clinical sequelae. Two vaccines
      against HPV have been developed recently that have shown to be safe and
      effective. The use of HPV vaccines holds promise for alleviating the burden of
      illness related to HPV infection. However, barriers specific to HPV vaccines, as
      well as barriers related to adolescent vaccination in general, may pose
      challenges to widespread implementation. Among these are: (1) lack of knowledge
      among the US population about HPV transmission and its relation to cervical
      cancer and other anogenital diseases; (2) parental concerns about vaccines in
      general and about vaccinating minors against sexually transmitted diseases; (3)
      financing by the government and private insurers for newly recommended vaccines;
      (4) challenges related to adolescents' healthcare-seeking behavior and health
      insurance coverage; and (5) barriers related to the dynamics of HPV infection
      (eg, protection against only certain types of HPV, duration of immunity,
      immunization schedules). Addressing these concerns will be critical in effective
      implementation of HPV vaccines and, potentially, vaccines, against other sexually
      transmitted diseases.

PMID- 17203994
TI  - Private idiotypes located on light and heavy chains of human myeloma proteins
      characterized by monoclonal antibodies.
AB  - Idiotypic determinant, an epitope located on the variable region of the heavy or
      light chain of an immunoglobulin molecule, could be classified into private and
      public forms. The private idiotype is a marker unique to a single clone of B cell
      and hence a fingerprint of an individual clone. It could therefore be exploited
      to monitor expansion of normal or malignant B cells and to target clonally
      expanded tumorous B cells specifically. In the present study, five murine
      monoclonal anti-idiotypic antibodies were generated against two human
      immunoglobulin G (IgG) myeloma proteins. These monoclonal antibodies (MAbs) are
      produced by hybridoma clones obtained by the fusion of myeloma cells with
      splenocytes from BALB/c mice immunized with either human IgG1 (three clones) or
      IgG2 (two clones) myeloma proteins. All MAbs reacted only with the immunizing
      antigens and had no reactivity with a panel of purified myeloma proteins of four
      IgG subclasses with different light chains, including IgG1 (n = 9), IgG2 (n = 4),
      IgG3 (n = 4) and IgG4 (n = 5). They reacted with the Fab, but not the Fc fraction
      of the immunizing antigen and displayed no reactivity with normal human serum or
      polyclonal IgG. Immunoblotting analysis demonstrated that two of the MAbs react
      with linear idiotypes on light chain, whereas the remaining three MAbs recognize
      heavy chain associated idiotopes, either conformational (n = 2) or linear (n =
      1). Such MAbs with specificity for private idiotypes could have potential
      implications for monitoring and specific immunotherapy of B cell malignancies.
      They also are useful tools to study structural correlates of idiotypes.

PMID- 17203995
TI  - Identification and characterization of a lysosomal membrane protein of
      Dictyostelium discoideum with monoclonal antibodies.
AB  - Lysosomes are responsible for the degradation of macromolecules derived from the
      cell exterior by endocytosis, or from within the cell by autophagy. While our
      knowledge of the biosynthesis and targeting of lysosomal hydrolases is
      considerable, much less is known about the lysosomal membrane itself. To identify
      the lysosomal membrane proteins that mediate these functions, we have isolated
      lysosomes from amebae and injected them into mice to produce monoclonal
      antibodies (MAbs). We produced nine MAbs against Dictyostelium lysosomes from the
      batches of fused cells. Among them, three MAbs were specific to lysosomal
      membrane and gave a strong signal, and thus used in this study. The MAbs
      specifically reacted with a single protein band of 27 kd and stained a lysosome
      like structure by immunofluorescence microscopy. To identify the antigen that the
      MAbs recognize, we processed differential centrifugation with whole-cell extract
      of Dictyostelium and traced p27 protein by activity assay of organelle marker
      enzyme. We showed that p27 is one component of the lysosomal system on the basis
      of comigration with a lysosomal marker enzyme. We also demonstrated that the 27
      kd lysosomal protein is a tightly bound integral membrane protein by using a
      phase separation method of Triton X-114.

PMID- 17203996
TI  - Preparation and characterization of monoclonal antibodies against mouse Jab1/CSN5
      protein.
AB  - Jab1, also known as the fifth component of the COP9 signalosome complex (CSN5),
      directly interacts with and regulates the activity and stability of multiple
      intracellular regulatory molecules, such as c-Jun, p27, p53, Cullin, Smad4, and
      HIF1alpha. In addition, a high level of Jab1 is observed in a variety of human
      cancers and is sometimes correlated with a poor prognosis, suggesting that Jab1
      contributes to cancer cell proliferation and survival and could be a novel target
      of cancer therapy. In this report, we generated five mouse monoclonal antibodies
      to a bacterially produced recombinant mouse Jab1 protein and examined their
      capabilities and limitations in commonly used assays, including enzyme linked
      immunosorbent assay (ELISA), Western blotting with denatured and native
      polyacrylamide gel electrophoresis (PAGE), immunoprecipitation, and
      immunofluorescence microscopy, finding the most suitable antibody for each
      application. Because these antibodies proved useful for immunohistochemical
      staining for Jab1 in fixed sections of human cancer samples, they should be
      useful in determining the expression and subcellular distribution of Jab1 in
      human tumors.

PMID- 17203997
TI  - Characterization of monoclonal antibodies to human soluble MD-2 protein.
AB  - Toll-like receptors (TLRs) are mammalian innate immune recognition receptors that
      are activated by pathogen associated molecular patterns (PAMPs). TLR4 is the
      signaling molecule of the lipopolysaccharide (LPS) receptor complex. TLR4
      associates with its adapter molecule, MD-2, which is absolutely required for LPS
      induced activation of TLR4. MD-2 exists as a cell surface protein in association
      with TLR4 and as secreted forms consisting of MD-2 monomers and multimers. To
      facilitate the studies of MD-2 distribution, abundance, and function, we produced
      monoclonal antibodies (MAbs) to baculovirally expressed soluble MD-2 (sMD-2).
      Eleven MAbs were characterized by enzyme-linked immunosorbent assay (ELISA) with
      soluble TLR4/MD-2 complex (sTLR4/MD-2) and sMD-2, Western blotting against sMD-2
      monomer and multimers, and inhibition of direct LPS binding to sMD-2. Four MAbs
      preferentially recognized mainly MD-2 oligomers, not monomers, as judged by
      Western blotting and ELISA. Anti-MD-2 MAbs useful for indirect immunofluorescent
      staining of cells expressing TLR4 and MD-2 were identified. One MAb that
      recognized all forms of MD-2 was used in an ELISA to measure sMD-2 in normal
      human sera as well as sera from intensive care patients with and without sepsis.
      Serum levels of sMD-2 were undetectable or very low in normal and in nonsepsis
      patients but significantly (p < 0.05) increased in sepsis patients. These MAbs
      should therefore be very useful new tools for studies of MD-2 expression and
      function in health and disease.

PMID- 17203998
TI  - Development and characterization of novel monoclonal antibodies against tartrate
      resistant acid phosphatase 5.
AB  - Serum band 5 tartrate-resistant acid phosphatase (TRACP 5; EC 3.1.3.2) is a
      glycoprotein that exists as two very similar isoforms, TRACP 5a and TRACP 5b. The
      similarity of these two isoforms has made it difficult to establish monoclonal
      antibodies specific for either isoform. We report here the development of a
      monoclonal antibody with high specificity for TRACP 5b. We prepared TRACP 5b
      antigens from four sources: TRACP 5b purified from human bone, recombinant TRACP
      5 from Escherichia coli, recombinant TRACP 5 from insect cells, and a synthetic
      TRACP 5b peptide. Thirty-seven mice were each immunized with 1 of the 4 different
      TRACP antigens to generate 473 antibody-producing clones. Three of these clones,
      Trk27, Trk49, and Trk62, reacted with TRACP 5b. These three clones were all
      established from mice exposed to native bone TRACP 5b antigen. In fact, none of
      the other antigens were able to generate anti-TRACP 5b monoclonal antibodies in
      mice. Furthermore, Trk62 interacted more strongly with TRACP 5b than with TRACP
      5a. These results suggested that although recombinant proteins can be effective
      antigens, the native TRACP 5 protein might be more effective at generating
      monoclonal antibodies of greater specificity due to its more faithful
      representation of the native three-dimensional structure of the protein.

PMID- 17203999
TI  - Preparation and characterization of a monoclonal antibody specific to Plasmodium
      falciparum TATA binding protein.
AB  - PfTBP is a transcriptional factor required by all three types of RNA polymerases
      in eukaryotic cells. In order to obtain a specific monoclonal antibody (MAb)
      against PfTBP, a DNA fragment of 684 base pairs (bp) that contained the complete
      PfTBP gene was amplified by polymerase chain reaction (PCR) and inserted into the
      pGEX prokaryotic expression vector. The recombinant protein (GST-PfTBP) was
      expressed in Escherichia coli, purified, and used as antigen to immunize mice.
      MAbs against PfTBP were obtained and hybridomas were screened by enzyme-linked
      immunosorbent assay (ELISA). Western blotting and immunofluorescence assays
      showed that MAb Pf.r1 recognized the PfTBP protein in nuclear extracts from
      Plasmodium falciparum as well as a native protein in the nuclei of this parasite.
      This MAb will be a helpful tool for the identification of the TBP associated
      factors (TAFs), which are apparently highly divergent with other eukaryotes. This
      information could help to identify new candidate gene products to develop novel
      drugs or vaccines.

PMID- 17204000
TI  - Comparative analysis of a monoclonal antibody-based Streptococcus mutans
      detection method with selective culture assays using polymerase chain reaction as
      a gold standard.
AB  - The aim of this study was to compare a recently developed monoclonal antibody
      (MAb)-based salivary Streptococcus mutans detection method with various selective
      media using polymerase chain reaction (PCR) as the gold standard. Salivary S.
      mutans cells were enumerated with a MAb-based method, along with three commonly
      used selective media, mitis-salivarius-bacitracin agar (MSB), trypticase yeast
      extract cystine sucrose bacitracin agar (TYCSB), and glucose-sucrose-potassium
      tellurite-bacitracin (GSTB) agar. Statistical analysis showed no significant
      correlations between each method. With PCR as the standard, a MAb-based detection
      method was found to provide the highest sensitivity (91%) and specificity (96%)
      among these four methods. This study demonstrates that the MAb-based detection
      method may provide more accurate enumeration of salivary S. mutans than selective
      media.

PMID- 17204001
TI  - Preparation and characterization of a specific monoclonal antibody against a new
      gene product: URG11.
AB  - As a new gene, the monoclonal antibody against URG11 protein is not currently
      available. In this study, one monoclonal antibody (MAb) against URG11 was
      obtained with standard cell fusion technique and enzymelinked immunosorbent assay
      (ELISA) screening. The peptide of URG11 used in making the MAb in this study was
      synthesized as described. One of the newly developed MAbs is named MAb 3D2, the
      isotype of which is IgG2a. Immunohistochemistry and Western blot showed that MAb
      3D2 could recognize URG11 protein in both native and denatured forms. MAb 3D2
      will be a useful tool for the functional research of URG11 in future studies.

PMID- 17204009
TI  - Simple models of assortment through environmental feedback.
AB  - Social evolution depends critically on assortment, or segregation versus even
      mixing, between cooperators and noncooperators. Altruistic traits, which reduce
      the absolute fitness of their bearers, cannot evolve without positive assortment
      (excess segregation). The question of how positive assortment can arise has been
      controversial, but most evolutionary biologists believe that common descent is
      the only effective general mechanism. Here I investigate another recently
      proposed mechanism for generating nonrandom assortment, termed environmental
      feedback. This requires only that two forms of a trait affect the quality of the
      local environment differently in such a way that all individuals are more likely
      to leave low-quality locales. Experiments with simple computational models
      confirm that environmental feedback generates significant levels of genetic
      similarity among non-kin within locales. The mechanism is fairly general, and can
      under some conditions produce levels of genetic similarity comparable to those
      resulting from close genealogical relationship. Environmental feedback can also
      generate the negative assortment necessary for the evolution of spiteful traits.
      Environmental feedback is expected to create positive frequency-dependent
      selection, which thus favor any social trait that becomes common in the
      population. Results from this stylized model suggest that environmental feedback
      could be important in the evolution of both cooperation and spite, within as well
      as between species.

PMID- 17204011
TI  - The dynamic changes in roles of learning through the Baldwin effect.
AB  - The interaction between evolution and learning called the Baldwin effect is a two
      step evolutionary scenario caused by the balances between benefit and cost of
      learning in general. However, little is known about the dynamic evolution of
      these balances in complex environments. Our purpose is to give a new insight into
      the benefit and cost of learning by focusing on the quantitative evolution of
      phenotypic plasticity under the assumption of epistatic interactions. For this
      purpose, we have constructed an evolutionary model of quantitative traits by
      using an extended version of Kauffman's NK fitness landscape. Phenotypic
      plasticity is introduced into our model; whether each phenotype is plastic or not
      is genetically defined, and plastic phenotypes can be adjusted by learning. The
      simulation results clearly show that drastic changes in roles of learning cause
      three-step evolution through the Baldwin effect and also cause the evolution of
      genetic robustness against mutations. We also conceptualize four different roles
      of learning by using a hill-climbing image of a population on a fitness
      landscape.

PMID- 17204010
TI  - Evolvable self-reproducing cells in a two-dimensional artificial chemistry.
AB  - We present a novel unit of evolution: a self-reproducing cell in a two
      dimensional artificial chemistry. The cells have a strip of genetic material that
      is used to produce enzymes, each catalyzing a specific reaction that may affect
      the survival of the cell. The enzymes are kept inside the cell by a loop of
      membrane, thus ensuring that only the cell that produced them gets their benefit.
      A set of reaction rules, each simple and local, allows the cells to copy their
      genetic information and physically divide. The evolutionary possibilities of the
      cells are explored, and it is suggested that the system provides a useful
      framework for testing hypotheses about self-driven evolution.

PMID- 17204012
TI  - The effects of cultural learning in populations of neural networks.
AB  - Population learning can be described as the iterative Darwinian process of
      fitness-based selection and genetic transfer of information leading to
      populations of higher fitness and is often simulated using genetic algorithms.
      Cultural learning describes the process of information transfer between
      individuals in a population through non-genetic means. Cultural learning has been
      simulated by combining genetic algorithms and neural networks using a teacher
      pupil scenario where highly fit individuals are selected as teachers and instruct
      the next generation. By examining the innate fitness of a population (i.e., the
      fitness of the population measured before any cultural learning takes place), it
      is possible to examine the effects of cultural learning on the population's
      genetic makeup. Our model explores the effect of cultural learning on a
      population and employs three benchmark sequential decision tasks as the
      evolutionary task for the population: connect-four, tic-tac-toe, and blackjack.
      Experiments are conducted with populations employing population learning alone
      and populations combining population and cultural learning. The article presents
      results showing the gradual transfer of knowledge from genes to the cultural
      process, illustrated by the simultaneous decrease in the population's innate
      fitness and the increase of its acquired fitness measured after learning takes
      place.

PMID- 17204013
TI  - Using the XCS classifier system for multi-objective reinforcement learning
      problems.
AB  - We investigate the performance of a learning classifier system in some simple
      multi-objective, multi-step maze problems, using both random and biased action
      selection policies for exploration. Results show that the choice of action
      selection policy can significantly affect the performance of the system in such
      environments. Further, this effect is directly related to population size, and we
      relate this finding to recent theoretical studies of learning classifier systems
      in single-step problems.

PMID- 17204017
TI  - Barrett's oesophagus--a pathologist's view.
AB  - Barrett's oesophagus, a precancerous condition for oesophageal adenocarcinoma,
      detected on endoscopy and confirmed on histology, shows intestinal metaplasia of
      the lower oesophagus. The significance of microscopic foci of intestinal
      metaplasia at the gastro-oesophageal junction, corresponding either to so-called
      'ultrashort' segment Barrett's oesophagus, or to carditis with intestinal
      metaplasia, is still a matter of debate. The surveillance of patients with
      Barrett's oesophagus is still based on systematic biopsy sampling of Barrett's
      mucosa on endoscopy, looking for dysplasia. Although well-established
      classifications of dysplasia are now used by most pathologists, there remain
      numerous problems with this subjective marker (sampling, diagnostic
      reproducibility, natural history, etc). Therefore, many alternative biomarkers
      have been proposed, but only DNA aneuploidy, proliferation markers and p53 loss
      of heterozygosity/overexpression have been shown to be of some use at the present
      time. Some endoscopic improvements already allow a better selection of biopsies,
      and it may be that in future new technologies will allow 'virtual biopsies'. On
      the other hand, the role of pathologists now extends to the evaluation of new
      therapeutic modalities of early neoplastic lesions in Barrett's oesophagus,
      especially endoscopic mucosal resection.

PMID- 17204018
TI  - Pathology of non-infective gastritis.
AB  - The discovery of Helicobacter pylori and its intimate role in the development of
      the most common form of chronic gastritis has elicited a much-needed interest in
      non-neoplastic gastric pathology. This has been paralleled by an increase in
      upper endoscopic examinations, which allow recognition of novel patterns and
      distribution of mucosal injury. Numerous attempts at classification have been
      made, most based on the acuteness or chronicity of gastric mucosal injury. In
      this review, we will not offer a new classification but present a detailed
      description of the major clinicopathological entities, based either on the
      salient morphological features or the underlying aetiologies, i.e. iatrogenic,
      autoimmune, vascular or idiopathic.

PMID- 17204019
TI  - Endocrine tumours of the gastrointestinal tract-selected topics.
AB  - This review provides an update on the pathogenesis and histopathological
      diagnosis of endocrine tumours of the gastrointestinal tract, concentrating on
      three different varieties whose careful assessment by pathologists is of
      particular clinical significance. These are the four types of enterochromaffin
      like cell tumour of the gastric corpus, the periampullary somatostatin-containing
      D-cell tumour of the duodenum, and the frequently chromogranin A-negative L-cell
      tumour of the appendix and large intestine. In addition, the value of
      pathological factors in predicting the behaviour of gastrointestinal endocrine
      tumours and selecting therapy is discussed, and the crucial role of the
      pathologist in the multidisciplinary team management of these neoplasms is
      emphasized.

PMID- 17204020
TI  - Gastrointestinal lymphoproliferative disorders.
AB  - Malignant lymphomas can be first detected in some patients in endoscopic biopsies
      of the gastrointestinal (GI) tract. However, their recognition and accurate
      classification often pose problems for the pathologist for several reasons.
      First, the small sampling size limits pattern recognition and the number of
      ancillary studies which can be performed. Second, the immune system of the GI
      tract is capable of intense hyperplastic responses which may mimic lymphoma.
      Third, in a fashion similar to cutaneous lesions, those in the alimentary tract
      may be visualized and biopsied at a very early phase in their development when
      differentiation into neoplasia may be incomplete. Some forms of immune response
      actually pass through a poorly defined transition into lymphoma. Examples of such
      'dysplasia' of the gut immune system include Helicobacter gastritis, coeliac
      disease and multicentric lymphoid hyperplasia associated with underlying
      immunodeficiency. With ever increasing endoscopic scrutiny of the gut by
      gastroenterologists, it is not surprising that the frequency of these
      indeterminate cases seems to be growing. In combination with careful clinical
      correlation and conventional microscopic analysis, selective immunohistochemical
      studies currently constitute the most powerful ancillary method in the
      pathologist's effort to recognize and classify GI lymphomas accurately.

PMID- 17204021
TI  - Infective disorders of the gastrointestinal tract.
AB  - Gastrointestinal infections are a major cause of morbidity and mortality
      worldwide. Infectious organisms are often recovered by microbiological methods,
      but surgical pathologists may play a very valuable role in diagnosis. This review
      will focus on infective disorders of the gastrointestinal tract with an emphasis
      on enterocolitides caused by food- and water-borne pathogens. Diagnostic
      histological features of selected enteric infections will be emphasized,
      including those that mimic other inflammatory conditions of the gut (such as
      ischaemia or idiopathic inflammatory bowel disease), along with available
      diagnostic methods that can aid in diagnosis.

PMID- 17204022
TI  - The pathology of malabsorption: current concepts.
AB  - Intestinal malabsorption results from a wide variety of causes, which can most
      easily be organized into three groups. Maldigestion arises from problems with
      mixing or with digestive mediators, and includes post-gastrectomy patients and
      those with deficiencies of pancreatic or intestinal enzymes, or of bile salts.
      Mucosal and mural causes of malabsorption are abundant, and include gluten
      sensitive enteropathy, tropical sprue, autoimmune enteropathy, and HIV/AIDS
      related enteropathy, as well as mural conditions such as systemic sclerosis.
      Finally, microbial causes of malabsorption include bacterial overgrowth,
      Whipple's disease, and numerous infections or infestations that are most
      frequently seen in immunocompromised patients. An overview of the most common and
      interesting entities in each of these categories follows, along with a discussion
      of current concepts. Mucosal conditions and microbial causes of malabsorption are
      given special attention.

PMID- 17204023
TI  - Indeterminate colitis: definition, diagnosis, implications and a plea for
      nosological sanity.
AB  - In 1978, Price introduced the concept of indeterminate colitis to describe cases
      in which colonic resections had been undertaken for chronic inflammatory bowel
      disease (CIBD), but a definitive diagnosis of either of the classical types of
      CIBD, ulcerative colitis and Crohn's disease, was not possible. This was
      especially apposite in cases of acute fulminant disease of the colorectum. More
      recently, the term indeterminate colitis has been applied to biopsy material,
      when it has not been possible to differentiate between ulcerative colitis and
      Crohn's disease. In our opinion, and in those of other workers in this field, the
      term should be restricted to that originally suggested by Price. This then
      provides a relatively well-defined group of patients in whom the implications and
      management of the disease are becoming much clearer. Cases where there are only
      biopsies with CIBD, but equivocal features for ulcerative colitis and Crohn's
      disease, should be termed 'CIBD, unclassified', 'equivocal/non-specific CIBD' or
      IBD unclassified (IBDU), in line with recent recommendations. When the diagnosis
      is correctly restricted to colectomy specimens, there is now good evidence that
      the majority of cases will behave like ulcerative colitis. Furthermore, the
      diagnosis should not be a contraindication to subsequent pouch surgery. When the
      latter is undertaken, surgeons and patients can expect an increased complication
      rate, compared with classical ulcerative colitis, especially of pelvic sepsis,
      but most patients fare well. Only very occasional patients, around 10%, will
      eventually be shown to have Crohn's disease. This review describes the pathology
      of cases appropriately classified as indeterminate colitis and the implications
      of that diagnosis. It also highlights recent advances in its pathological
      features, clinical management and its immunological and genetic associations.

PMID- 17204024
TI  - Histopathological mimicry in mucosal prolapse.
AB  - Mucosal prolapse solitary rectal ulcer syndrome is a condition which has
      frequently confused both pathologists and surgeons alike. Despite its recognition
      in the nineteenth century, it continues to be a diagnostic challenge. The
      significance of correctly diagnosing this condition is that it avoids the
      morbidity and mortality associated with major surgery or the side-effects of long
      term medical treatment. This review considers the histological features of
      mucosal prolapse and how it may mimic other pathological conditions.

PMID- 17204025
TI  - Reporting colorectal cancer.
AB  - The management of colorectal cancer is a team process. High-quality reporting of
      colorectal cancer is very important as the whole team relies upon the skill of
      the pathologist. Failure to report key features can lead to undertreatment of
      this disease. The use of a proforma has been demonstrated to be beneficial and we
      recommend staying with TNM5 due to scientific and reproducibility issues with
      TNM6. Important features in stage II/Dukes' B cases are extramural vascular
      invasion, peritoneal involvement, extent of extramural spread, incomplete
      resection and perforation. All of these may lead to adjuvant therapy being
      administered. The surgically created circumferential resection margin (CRM) and
      the mode of its creation are important features and the CRM retains its value
      after preoperative therapy. Regression grading should be applied only to fully
      resected tumours and the dissection and sampling must be standardized to allow
      comparison of results between trials and centres. When reporting local resections
      of early-stage cancers we need to look for features that predict spread to local
      lymph nodes to allow a full resection to be considered.

PMID- 17204026
TI  - Classification of colorectal cancer based on correlation of clinical,
      morphological and molecular features.
AB  - Over the last 20 years it has become clear that colorectal cancer (CRC) evolves
      through multiple pathways. These pathways may be defined on the basis of two
      molecular features: (i) DNA microsatellite instability (MSI) status stratified as
      MSI-high (MSI-H), MSI-low (MSI-L) and MS stable (MSS), and (ii) CpG island
      methylator phenotype (CIMP) stratified as CIMP-high, CIMP-low and CIMP-negative
      (CIMP-neg). In this review the morphological correlates of five molecular
      subtypes are outlined: Type 1 (CIMP-high/MSI-H/BRAF mutation), Type 2 (CIMP
      high/MSI-L or MSS/BRAF mutation), Type 3 (CIMP-low/MSS or MSI-L/KRAS mutation),
      Type 4 (CIMP-neg/MSS) and Type 5 or Lynch syndrome (CIMP-neg/MSI-H). The
      molecular pathways are determined at an early evolutionary stage and are fully
      established within precancerous lesions. Serrated polyps are the precursors of
      Types 1 and 2 CRC, whereas Types 4 and 5 evolve through the adenoma-carcinoma
      sequence. Type 3 CRC may arise within either type of polyp. Types 1 and 4 are
      conceived as having few, if any, molecular overlaps with each other, whereas
      Types 2, 3 and 5 combine the molecular features of Types 1 and 4 in different
      ways. This approach to the classification of CRC should accelerate understanding
      of causation and will impact on clinical management in the areas of both
      prevention and treatment.

PMID- 17204027
TI  - Colorectal serrated adenocarcinoma.
AB  - Colorectal cancer (CRC) ranks among the three most common cancers in terms of
      both cancer incidence and cancer-related deaths in most Western countries.
      Serrated adenocarcinoma is a recently described, distinct variant of CRC,
      accounting for about 7.5% of all CRCs and up to 17.5% of most proximal CRCs. It
      has been postulated that about 10-15% of sporadic CRCs would have their origin in
      serrated polyps that harbour a significant malignant potential. These lesions
      include hyperplastic-type aberrant crypt foci, hyperplastic polyps, sessile
      serrated adenomas, admixed polyps and serrated adenomas, and constitute the so
      called 'serrated pathway', which is distinct from both the conventional adenoma
      carcinoma pathway and the mutator pathway of hereditary non-polyposis CRC and is
      characterized by early involvement of oncogenic BRAF mutations, excess CpG island
      methylation (CIM) and subsequent low- or high-level DNA microsatellite
      instability (MSI). Methylation of hMLH1 is likely to explain the increased
      frequency of high-level MSI (16%) and methylation of MGMT is postulated to
      explain the low-level MSI (29%) in serrated adenocarcinomas. Reproducible
      histopathological criteria for serrated adenocarcinoma have recently been
      established and they have been qualified by DNA expression analysis for 7928
      genes, showing clustering of serrated adenocarcinomas into a molecular entity
      apart from conventional adenocarcinoma, and representing with distinct down
      regulation of EPHB2, PTCH and up-regulation of HIF1alpha.

PMID- 17204028
TI  - Tumour budding in colorectal carcinoma.
AB  - The term tumour budding denotes that at the invasion front of colorectal
      adenocarcinomas tumour cells, singly or in small aggregates, become detached from
      the neoplastic glands. This morphological feature is increasingly being
      recognized as a strong and robust adverse prognostic factor. Biologically, tumour
      budding is closely related to the epithelial-mesenchymal transition. In this
      review the morphological features of tumour budding are discussed, as observed by
      the surgical pathologist reporting colorectal carcinoma resection specimens. The
      morphological features are put into context with the rapidly expanding knowledge
      of the epithelial-mesenchymal transition in general, and the molecular pathology
      of colorectal carcinoma in particular. Finally, a systematic analysis of the
      relevant published clinicopathological studies emphasizes the potential of tumour
      budding as a prognostic factor for routine surgical pathology.

PMID- 17204029
TI  - Poorly differentiated tumours of the anal canal: a diagnostic strategy for the
      surgical pathologist.
AB  - Poorly differentiated malignancies affecting the anal canal are uncommon but pose
      diagnostic difficulties because of the wide range of normal cell types that may
      occur within a limited anatomical region. The range of lesions that may present
      as poorly differentiated tumours includes squamous cell carcinoma,
      adenocarcinoma, small and large cell neuroendocrine carcinoma, neuroendocrine
      carcinoma expressing epithelial cytokeratins and other patterns of mixed
      differentiation, undifferentiated carcinoma, malignant melanoma, lymphoma and
      secondary tumours. This review discusses the differential diagnosis of these
      neoplasms with the aid of short illustrative case studies.

PMID- 17204030
TI  - CO2 elimination at varying inspiratory pause in acute lung injury.
AB  - Previous studies have indicated that, during mechanical ventilation, an
      inspiratory pause enhances gas exchange. This has been attributed to prolonged
      time during which fresh gas of the tidal volume is present in the respiratory
      zone and is available for distribution in the lung periphery. The mean
      distribution time of inspired gas (MDT) is the mean time during which fractions
      of fresh gas are present in the respiratory zone. All ventilators allow setting
      of pause time, T(P), which is a determinant of MDT. The objective of the present
      study was to test in patients the hypothesis that the volume of CO(2) eliminated
      per breath, V(T)CO(2), is correlated to the logarithm of MDT as previously found
      in animal models. Eleven patients with acute lung injury were studied. When T(P)
      increased from 0% to 30%, MDT increased fourfold. A change of T(P) from 10% to 0%
      reduced V(T)CO(2) by 14%, while a change to 30% increased V(T)CO(2) by 19%. The
      relationship between V(T)CO(2) and MDT was in accordance with the logarithmic
      hypothesis. The change in V(T)CO(2) reflected to equal extent changes in airway
      dead space and alveolar PCO(2) read from the alveolar plateau of the single
      breath test for CO(2). By varying T(P), effects are observed on V(T)CO(2), airway
      dead space and alveolar PCO(2). These effects depend on perfusion, gas
      distribution and diffusion in the lung periphery, which need to be further
      elucidated.

PMID- 17204031
TI  - Effect of fat digestion on superior mesenteric artery blood flow in humans.
AB  - BACKGROUND AND AIM: Intraluminal nutrients stimulate superior mesenteric artery
      (SMA) blood flow. Of the macronutrients, especially fat affects the magnitude of
      the SMA blood flow response to a meal. Little is known however on the influence
      of fat hydrolysis on SMA flow. METHODS: We compared in eight healthy volunteers
      the SMA flow response (Doppler ultrasonography) to continuous intraduodenal fat
      perfusion (LCT, 240 kCal h(-1)) during conditions with normal hydrolysis
      (placebo, control), increased hydrolysis (pancreatic enzyme supplementation; 50
      kU lipase) and impaired hydrolysis (orlistat 240 mg). RESULTS: Intraduodenal LCT
      significantly (P<0.01) increased SMA flow in all experiments over basal. The SMA
      flow response to fat during pancreatic enzyme supplementation (1.49 +/- 0.1 l
      min(-1)) was significantly (P<0.05) higher compared with placebo (1.11 +/- 0.16 l
      min(-1)). Lipase inhibition with orlistat did not significantly affect fat
      stimulated SMA flow compared with placebo: 0.89 +/- 0.08 l min(-1) versus 1.11 +/
      0.16 l min(-1). CONCLUSIONS: Administration of pancreatic enzymes significantly
      increases fat stimulated SMA flow. Fat digest products in the intestinal lumen
      contribute to the regulation of SMA blood flow.

PMID- 17204032
TI  - BMI and objectively measured body fat and body fat distribution in prepubertal
      children.
AB  - BACKGROUND: Body Mass Index (BMI) is often used as a surrogate estimate of body
      fat in epidemiological studies. This study explores the association between BMI,
      body fat and body fat distribution assessed by Dual-Energy X-Ray Absorptiometry
      (DXA) in younger children. METHODS: Cross-sectional study of 246 children (138
      boys and 108 girls) aged 8-11 years. DXA was used to quantify abdominal fat mass
      (AFM), total body fat (TBF) and also total body fat as percentage of total body
      mass (BF%). Body fat distribution was calculated as AFM/TBF. RESULTS: We found
      close correlations between BMI vs. TBF, BF% and AFM (r = 0.94, r = 0.92 and r =
      0.93) for boys and (r = 0.95, r = 0.92 and r = 0.95) for girls, respectively
      (P<0.05 for all r-values). However, significantly lower correlation (P<0.001 for
      difference between the r-values) existed for body fat distribution (r = 0.64 for
      boys and 0.73 for girls). CONCLUSION: Percentage body fat, TBF and AFM were all
      closely associated with BMI, suggesting that BMI serves as a good surrogate
      marker for obesity in population studies. However, a significantly lower
      correlation existed for BMI vs. body fat distribution, which may be a limitation
      when BMI is used to study cardiovascular risk factors in epidemiological studies.

PMID- 17204033
TI  - Volumetric evaluation of upper extremities in 250 healthy persons.
AB  - BACKGROUND AND PURPOSE: Upper extremity oedema frequently occurs as a
      complication of several diseases. The aim of this study was to establish
      normative data for upper extremity volumes with a modified water displacement
      method. These data were used to develop predictive formulas helpful in detecting
      abnormal swelling. SUBJECTS AND METHODS: Upper extremities of 250 healthy
      subjects (138 men and 112 women) were measured by water displacement. RESULTS: A
      mean difference of 3.0% (3.2%) between right and left arm (forearm) was found.
      Intra-class correlation coefficients were 0.99 for intra-rater and inter-rater
      reliabilities. Coefficient of variation was 0.23%. To predict the premorbid
      volume of an oedematous arm, prediction formulas were constructed. DISCUSSION AND
      CONCLUSION: Water displacement as used in this study is a highly reliable
      technique for volume measurement of upper extremities. This technique was applied
      to gather normative data for upper extremity volumes. We suggest that this
      technique can be used in daily clinical practice for the evaluation of upper
      extremity oedema or atrophy caused by various diseases as well as for volume
      monitoring. Prediction formulas can be used to define abnormal swelling.

PMID- 17204034
TI  - Nasal indices of eosinophilic and exudative inflammation in bakery-workers.
AB  - AIMS: Rhinitis symptoms frequently occur in bakery-workers. Yet, little is known
      about the pathophysiology of this condition. The objective of the present study
      was to examine nasal indices of inflammation in relation to occupational dust
      exposure, occupational rhinitis according to defined criteria, rhinitis symptoms
      associated to the workplace, and occupational sensitization in bakery-workers.
      METHODS: Bakery-workers (n = 197) were subjected to interviews, questionnaires,
      workplace dust measurements, allergy tests, and nasal lavages with and without
      histamine. alpha(2)-Macroglobulin and eosinophil cationic protein (ECP) were
      measured in saline lavages as indices of plasma exudation and eosinophilic
      activity, respectively. Histamine lavages were employed to explore the nasal
      exudative responsiveness. RESULTS: alpha(2)-Macroglobulin and ECP increased
      significantly by increased workplace dust exposure (P< or =0.035). Furthermore,
      the exudative responsiveness to histamine increased significantly by such
      exposure (P< or =0.016). Similar patterns were seen in workers with occupational
      rhinitis and in subjects with rhinitis symptoms associated to the workplace, but
      not in workers with occupational sensitization. CONCLUSIONS: We conclude that
      occupational dust exposure in bakery-workers is associated with nasal
      eosinophilic exudative inflammation. In contrast, occupational sensitization is
      not a discriminating factor with regard to indices of eosinophilic, exudative
      inflammation in the present material.

PMID- 17204035
TI  - Myocardial ischaemia in patients with peripheral arterial disease.
AB  - AIM: To study the relation between myocardial ischemia assessed with different
      techniques in patients with peripheral arterial disease (PAD) in comparison with
      a matched control group. METHODS: Ninety-nine male patients with PAD and 94 age-
      and sex-matched control subjects without PAD or ischaemic heart disease performed
      a exercise treadmill test, dipyridamole Tc-99m sestamibi myocardial perfusion
      SPECT (MPS) (43 controls) and 48-h ambulatory ECG (AECG)-monitoring (43
      controls). RESULTS: Thirteen of 99 patients had irreversible and 24 of 99 had
      reversible perfusion defects in MPS in comparison with 0 of 43 and six of 43 of
      control subjects respectively (P<0.01). Thirteen of 84 evaluable patients
      experienced a total of 36 episodes of ST-depression in AECG in comparison with
      two episodes in two of 42 control subjects (P = 0.07). Out of 13 patients with ST
      depression episodes only three had reversible ischaemia in MPS. CONCLUSION: Most
      PAD patients with episodes of ST-segment depression have no reversible ischaemia
      as assessed with dipyridamole-stress MPS. Episodes of ST-segment depression may
      reflect types of myocardial ischaemia that are different from those detected by
      MPS.

PMID- 17204036
TI  - Echocardiographic Doppler assessments of left ventricular filling and ejection
      during upright exercise in endurance athletes.
AB  - Doppler echocardiography was used to describe left ventricular filling and
      ejection during upright bicycle exercise in 24 healthy male endurance athletes.
      The transmitral pressure gradient was estimated and isovolumetric relaxation,
      filling and ejection time and transmitral and aortic flow velocities were
      measured at rest and during exercise. From rest to peak exercise (at a heart rate
      of 160 bpm), the mean left ventricular filling time was shortened by 73%, the
      ejection time by 31%, while the isovolumetric relaxation time was shortened by
      62%. At peak exercise, the maximum aortic flow velocity almost doubled and the
      maximum transmitral flow velocity more than doubled, with a tenfold increase in
      the mean transmitral pressure gradient. The increase was significant (P<0.001) at
      each level of exercise. The left ventricular filling rate measured as volume per
      time was 185 +/- 62 ml s(-1) at rest and it increased to 986 +/- 192 ml s(-1) at
      peak exercise. This study demonstrates large changes in diastolic filling indices
      during upright exercise and it shows that the heart is able to increase its
      filling rate five times from rest to peak exercise.

PMID- 17204037
TI  - Reliability and validity of the lung volume measurement made by the BOD POD body
      composition system.
AB  - The BOD POD Body Composition System uses air-displacement plethysmography to
      measure body volume. To correct the body volume measurement for the subject's
      lung volume, the BOD POD utilizes pulmonary plethysmography to measure functional
      residual capacity (FRC) at mid-exhalation as that is the subject's lung volume
      during the body volume measurement. Normally, FRC is measured at end-exhalation.
      The BOD POD FRC measurement can be corrected to an end-exhalation volume by
      subtracting approximately one-half of the measured tidal volume. Our purpose was
      to determine the reliability and validity of the BOD POD FRC measurement at end
      exhalation. Ninety-two healthy adults (half female) underwent duplicate FRC
      measurements by the BOD POD and one FRC measurement by a traditional gas dilution
      technique. The latter method was used as the reference method for the validity
      component of the study. The order of the FRC measurements by the two methods was
      randomized. The test-retest correlation coefficients for the duplicate BOD POD
      FRC measurements for the male and female subjects were 0.966 and 0.948,
      respectively. The mean differences between the BOD POD FRC trial #1 measurement
      and gas dilution FRC measurement for the male and female subjects were -32 and 
      23 ml, respectively. Neither difference was statistically significant. The
      correlation coefficients for these two measurements in the male and female
      subjects were 0.925 and 0.917, respectively. Based on these results, we conclude
      that the BOD POD FRC measurement in healthy males and females is both reliable
      and valid.

PMID- 17204038
TI  - The effect of mandibular advancement appliances on awake upper airway and
      masticatory muscle activity in patients with obstructive sleep apnoea.
AB  - BACKGROUND: There is little understanding of how dental appliances, designed to
      posture the mandible forwards, act on pharyngeal airway dilatory and masticatory
      muscles in patients with obstructive sleep apnoea (OSA). This study evaluates, in
      a prospective cohort design, the effect of mandibular advancement splints (MAS)
      on awake genioglossus (GG), geniohyoid (GH) and masseter (M) muscle activity.
      METHODS: Fifty OSA patients received a custom-made removable Herbst MAS
      appliance, adjusted for maximum therapeutic benefit, as judged by subjective
      improvement. Awake electromyographic (EMG) activity was recorded at baseline and
      with the MAS in situ, by using bipolar surface electrodes in patients seated
      upright and in the natural head position. The lower splint was modified to
      facilitate the placement of the intra-oral bipolar surface electrodes used to
      record GG EMG activity. RESULTS: Significant increases in GG (P = 0.041), GH
      (P<0.001) and M (P<0.001) muscle activity accompanied placement of the MAS.
      CONCLUSIONS: These findings support the contention of a physiological role, which
      may act to augment the anatomical action of MAS.

PMID- 17204039
TI  - Skin tissue water and laser Doppler blood flow during a menstrual cycle.
AB  - Previous work offers conflicting evidence concerning whether basal skin blood
      flow (SBF) varies with the menstrual cycle. Our goal was to determine the extent
      of cycle-dependent changes in forearm SBF parameters and if they are linked to
      local tissue water content and arm volume changes. Both arms of 10 premenopausal
      women were evaluated three times during their cycle (days 4, 12 and 22) and 10
      postmenopausal women were evaluated once. Each evaluation included laser Doppler
      blood flow parameters (perfusion, volume and velocity), skin temperature, arm
      volume and local tissue water determined by a new tissue dielectric constant
      method. Estradiol and progesterone concentrations were determined at each visit
      by using saliva samples and analysis showed the expected pattern of variation
      over the cycle. Main results showed no significant cycle-dependent variations in
      any SBF parameter, temperature, tissue water or arm volume. Postmenopausal women
      had significantly less estradiol levels, but did not differ with respect to
      premenopausal women in any measured parameter except for a slightly less blood
      velocity (P<0.01). We hypothesize that that the absence of changes in tissue
      water and arm volume in our group may account for the constancy of the measured
      SBF parameters. However, in other populations, hormonally induced tissue changes
      may occur and contribute to the cycle-dependent changes in resting blood
      perfusion that have been reported. This possibility suggests that it may be
      useful to measure and report a skin tissue water index when serial changes in
      blood perfusion are being investigated.

PMID- 17204040
TI  - Disturbed glucose metabolism is associated with left ventricular dysfunction
      using tissue Doppler imaging in patients with myocardial infarction.
AB  - AIMS: To investigate the association between glucose abnormalities and left
      ventricular (LV) function assessed by tissue Doppler imaging (TDI) in patients
      with previous history of myocardial infarction and without known diabetes
      mellitus. PATIENTS AND METHODS: In a cross-sectional study, 123 patients, aged 31
      80 years, with a history of previous myocardial infarction and without known
      diabetes mellitus were examined with TDI echocardiography. A standard oral
      glucose test (OGTT) with 75 g of glucose was performed. RESULTS: Two-hour plasma
      glucose were significantly and negatively associated with TDI parameters such as
      LV ejection time; early diastolic filling velocity (E'-v); ratio of the early to
      late diastolic filling velocity (E'/A') and positively associated with regional
      myocardial performance index (MPI) (P<0.05). Left ventricular ejection time and
      MPI were significantly higher; E'/A' and E'-v were significantly lower in
      patients with disturbed glucose metabolism compared with patients with normal
      glucose tolerance (P<0.01). These differences remain significant also when the
      patients with DM were excluded. CONCLUSIONS: The present study demonstrates that
      disturbed glucose metabolism is associated with more pronounced LV dysfunction
      using TDI in patients with myocardial infarction. These abnormalities in LV
      function were more common not only in subjects with diabetes, but also in
      patients with prediabetic condition, impaired glucose intolerance.

PMID- 17204041
TI  - The modular nature of genetic diseases.
AB  - Evidence from many sources suggests that similar phenotypes are begotten by
      functionally related genes. This is most obvious in the case of genetically
      heterogeneous diseases such as Fanconi anemia, Bardet-Biedl or Usher syndrome,
      where the various genes work together in a single biological module. Such modules
      can be a multiprotein complex, a pathway, or a single cellular or subcellular
      organelle. This observation suggests a number of hypotheses about the human
      phenome that are now beginning to be explored. First, there is now good evidence
      from bioinformatic analyses that human genetic diseases can be clustered on the
      basis of their phenotypic similarities and that such a clustering represents true
      biological relationships of the genes involved. Second, one may use such
      phenotypic similarity to predict and then test for the contribution of apparently
      unrelated genes to the same functional module. This concept is now being
      systematically tested for several diseases. Most recently, a systematic yeast two
      hybrid screen of all known genes for inherited ataxias indicated that they all
      form part of a single extended protein-protein interaction network. Third, one
      can use bioinformatics to make predictions about new genes for diseases that form
      part of the same phenotype cluster. This is done by starting from the known
      disease genes and then searching for genes that share one or more functional
      attributes such as gene expression pattern, coevolution, or gene ontology.
      Ultimately, one may expect that a modular view of disease genes should help the
      rapid identification of additional disease genes for multifactorial diseases once
      the first few contributing genes (or environmental factors) have been reliably
      identified.

PMID- 17204042
TI  - Diagnosis and management of early- and late-onset cerebellar ataxia.
AB  - Cerebellar ataxias represent a heterogeneous group of neurodegenerative
      disorders. Two main categories are distinguished: hereditary and sporadic
      ataxias. Sporadic ataxias may be symptomatic or idiopathic. The clinical
      classification of hereditary ataxias is nowadays being replaced by an expanding
      genotype-based classification. A large spectrum of degenerative and metabolic
      disorders may also present with ataxia early or late in the course of disease. We
      present a diagnostic algorithm for the adult patient presenting with subacute
      cerebellar ataxia, based on family history and straightforward clinical
      characteristics of the patient. Along with the algorithm, an overview of the
      autosomal dominant, autosomal recessive, X-linked, mitochondrial, symptomatic and
      idiopathic subtypes of cerebellar ataxia is presented. An appropriate diagnosis
      is of utmost importance to such considerations as prognosis, genetic counselling
      and possible therapeutic implications.

PMID- 17204043
TI  - The genetics of hydatidiform moles: new lights on an ancient disease.
AB  - Hydatidiform mole (HM) is a human pregnancy with no embryo but cystic
      degeneration of chorionic villi. The common form of this condition occurs in 1 in
      every 1500 pregnancies in western societies and at a higher incidence in some
      geographic regions and populations. Recurrent moles account for 2% of all molar
      cases and a few of them occur in more than one family member. By studying a
      familial form of recurrent moles, a recessive maternal locus responsible for this
      condition was mapped to 19q13.4 and causative mutations identified. The defective
      protein, NALP7, is part of the CATERPILLAR protein family with roles in pathogen
      induced inflammation and apoptosis. The exact role of NALP7 in the
      pathophysiology of molar pregnancies is unknown yet. NALP7 could have a role
      either in oogenesis or in the endometrium during trophoblast invasion and
      decidualization. In this review, we outlined recent advances in the field of HMs
      and reviewed the literature in the light of the new data.

PMID- 17204044
TI  - Family system characteristics and psychological adjustment to cancer
      susceptibility genetic testing: a prospective study.
AB  - This study examined prospectively the contribution of family functioning,
      differentiation to parents, family communication and support from relatives to
      psychological distress in individuals undergoing genetic susceptibility testing
      for a known familial pathogenic BRCA1/2 or Hereditary nonpolyposis colorectal
      cancer-related mutation. Family functioning, differentiation to parents,
      hereditary cancer-related family communication and perceived support from
      relatives were assessed in 271 participants for genetic testing before test
      result disclosure. Hereditary cancer distress (assessed by the Impact of Event
      Scale) and cancer worry (assessed by the Cancer Worry Scale) were assessed
      before, 1 week after, and 6 months after test result disclosure. Participants
      reporting more cancer-related distress over the study period more frequently
      perceived the communication about hereditary cancer with relatives as inhibited,
      the nuclear family functioning as disengaged-rigid or enmeshed-chaotic, the
      support from partner as less than adequate and the relationship to mother as less
      differentiated. Especially, open communication regarding hereditary cancer and
      partner support may be important buffers against hereditary cancer distress.
      Identifying individuals with insufficient sources of support and addressing the
      family communication concerning hereditary cancer in genetic counseling may help
      the counselee to adjust better to genetic testing.

PMID- 17204047
TI  - Hereditary hemochromatosis screening: effect of mutation penetrance and
      prevalence on cost-effectiveness of testing algorithms.
AB  - Screening for hereditary hemochromatosis, although largely discussed, is not yet
      implemented in clinical practice. We evaluated the cost-effectiveness of 165
      hemochromatosis population-screening algorithms involving two or three of several
      screening tests by developing a computer program that simulates all possible
      screening scenarios. Input data comprised government estimates of health services
      data and costs and a virtual population with user-defined demographic
      characteristics (including variable HFE mutation frequencies and penetrance
      values). We show that when C282Y homozygote prevalence is set at 3:1000,
      population screening appears cost-effective when penetrance of the biochemical
      phenotype is >0.70. When only hepatocellular carcinoma and cirrhosis are
      considered as the cost-driving complications, population-based screening is not
      significantly more cost-efficient than no screening, but life expectancy of
      individuals identified with hereditary hemochromatosis and treated is still
      improved by 7 years. Among the 165 screening algorithms tested in 91 different
      virtual populations of one million individuals, biochemical tests usually perform
      better as the initial test than genetic testing. Indeed, the genetic testing is
      most cost-effective as the final confirmatory test. Finally, for most
      combinations of prevalence and penetrance of HFE, one screening algorithm-
      unbound iron-binding capacity + transferrin saturation--appeared robust enough to
      be always within the top 5 most cost-effective strategies.

PMID- 17204048
TI  - The correlation of CTG repeat length with material and social deprivation in
      myotonic dystrophy.
AB  - Socioeconomic deprivation has long been recognized as a prominent feature of
      myotonic dystrophy type 1 (DM1), but studies performed before the discovery of
      the mutation causing DM1 may have suffered an ascertainment bias towards the more
      severe forms of the disease. We have sought to clarify the relationship between
      CTG repeats, muscular impairment, and socioeconomic characteristics of 200
      patients with DM1. Patients with DM1 reported lower educational attainment, lower
      employment rate, lower family income, and higher reliance on social assistance
      than the reference population. Logistic regression showed, on one hand, that CTG
      repeats and marital status were significant predictors of social assistance
      recipiency and, on the other hand, that CTG repeats and gender were significant
      predictors of low social support from family, after adjustment for age, gender,
      degree of muscular impairment, CTG repeats, educational level, and marital
      status. For example, each additional 100 CTG repeats was found to increase the
      odds of relying on social assistance by about 35% and having low social support
      by about 22%. The chances of experiencing socioeconomic deprivation are loaded
      heavily against patients with DM1. The relationship between increased CTG repeat
      length and higher risk of material and social deprivation must be acknowledged in
      the clinical management of DM1.

PMID- 17204049
TI  - Two novel translocation breakpoints upstream of SOX9 define borders of the
      proximal and distal breakpoint cluster region in campomelic dysplasia.
AB  - The semilethal skeletal malformation syndrome campomelic dysplasia (CD) with or
      without XY sex reversal is caused by mutations within the SOX9 gene on 17q24.3 or
      by chromosomal aberrations (translocations, inversions or deletions) with
      breakpoints outside the SOX9 coding region. The previously published CD
      translocation breakpoints upstream of SOX9 fall into two clusters: a proximal
      cluster with breakpoints between 50-300 kb and a distal cluster with breakpoints
      between 899-932 kb. Here, we present clinical, cytogenetic and molecular data
      from two novel CD translocation cases. Case 1 with karyotype
      46,XY,t(1;17)(q42.1;q24.3) has characteristic symptoms of CD, including mild
      tibial bowing, cryptorchidism and hypospadias. By standard fluorescence in situ
      hybridization (FISH) and by high-resolution fiber FISH, the 17q breakpoint was
      mapped 375 kb from SOX9, defining the centromeric border of the proximal
      breakpoint cluster region. Case 2 with karyotype 46,X,t(Y;17)(q11.2;q24.3) has
      the acampomelic form of CD and complete XY sex reversal. By FISH and somatic cell
      hybrid analysis, the 17q breakpoint was mapped 789 kb from SOX9, defining the
      telomeric border of the distal breakpoint cluster region. We discuss the
      structure of the 1 Mb cis-control region upstream of SOX9 and the correlation
      between the position of the 14 mapped translocation breakpoints with respect to
      disease severity and XY sex reversal.

PMID- 17204050
TI  - In search of a familial cancer risk assessment tool.
AB  - Approximately one in three individuals will be affected by cancer in their
      lifetime in the United States, and some are at elevated risk because of family
      history. Although assessment of family history of cancer and cancer risk is the
      standard of care, the current health-care system appears unable to meet this
      need. Because individuals are increasingly using the Internet, web-based cancer
      risk assessment tools (CRATs) may provide a way to meet this need. The purpose of
      this review was to evaluate the types of familial CRATs available on the Internet
      and their nature. The current review evaluated five CRATs identified through an
      Internet search based on (i) their ability to identify those at the highest risk
      of cancer (i.e. those with hereditary cancer syndromes), (ii) their strengths and
      limitations based on criteria adapted from Rich and colleagues (2004, 2005),
      (iii) their readability based on four readability calculations, and (iv) their
      quality based on criteria from Health on the Net. The general limitations of
      CRATs as a whole were also delineated, including concerns about availability to
      those who are poor and underserved and those who have lower levels of literacy.
      Recommendations for future tools include assessing risk for a greater number of
      diseases, using theoretically driven approaches to increase the likelihood that
      individuals will engage in appropriate health behaviors, and making a greater
      effort to reach diverse populations.

PMID- 17204051
TI  - Co-existence of two functional mutations on the same allele of the human
      ferrochelatase gene in erythropoietic protoporphyria.
AB  - Erythropoietic protoporphyria (EPP) is an autosomal dominant disease with
      incomplete penetrance due to reduced activity of ferrochelatase (FECH), a
      mitochondrial enzyme that catalyzes the final step of the heme biosynthetic
      pathway. The clinical phenotype of EPP results from co-inheritance of a mutated
      allele and a wild-type low-expressed allele of the FECH gene. To date, more than
      88 different mutations have been identified in the FECH gene of patients with
      EPP. There are evidences suggesting that an entire haplotype (-251G, IVS1-23T and
      IVS3-48C) reduces allele expression. In this study, we searched for the -251A/G,
      IVS1-23C/T and IVS3-48T/C polymorphisms in two unrelated Italian families with
      EPP. In all the patients, carrying the -250G>C mutation in the promoter region,
      the IVS3-48C on the other allele showed apparent homozygosity and absence of
      Mendelian segregation. By RNA and long polymerase chain reaction analysis, we
      identified a deletion of 5576 bp (g12490_18067), including exons 3 and 4, in cis
      with the -250G>C mutation in the promoter.

PMID- 17204052
TI  - Early lethal autosomal recessive enterocolitis: report of a second family.

PMID- 17204053
TI  - ENG mutations in MADH4/BMPR1A mutation negative patients with juvenile polyposis.

PMID- 17204054
TI  - Inheritance of a novel RYR1 mutation in a family with myotonic dystrophy type 1.

PMID- 17204055
TI  - Six novel mutations in the GCK gene in MODY patients.

PMID- 17204056
TI  - Prevalence of C282Y, H63D and S65C mutations of the hemochromatosis (HFE) gene in
      a population from southeastern Spain (Murcia Region).

PMID- 17204058
TI  - Vitreous cryo-sectioning of cells facilitated by a micromanipulator.
AB  - Sectioning vitrified cells and tissues for cryo-electron microscopy is more
      challenging than room-temperature sectioning of plastic-embedded samples. As the
      sample must be kept very cold (<-130 degrees C) and because there is no liquid
      upon which the sections can float as they are cut, transferring the sections from
      the knife edge to a grid is one of the more difficult steps in the process. We
      employed a micromanipulator to hold and control the cryo-sections as they come
      off the knife. This allows slower cutting speeds than are typically used in
      vitreous cryo-sectioning and contributes to better control during cutting, which
      facilitates repeatable placement of a ribbon of sections onto a grid. The ribbon
      is kept under tension during the entire cutting process, which may decrease
      folding and/or compression, features that are inherent to vitreous sections.
      Furthermore, the added control afforded by this technique makes it easier for
      multiple ribbons to be placed on a single grid, thereby increasing the number of
      sections that can be examined and imaged during a microscopy session. It even
      allows for serial cryo-electron microscopy. As such, this approach is an advance
      in the cryo-microtomy of vitreous sections.

PMID- 17204059
TI  - Comparison of two polymer-based immunohistochemical detection systems: ENVISION+
      and ImmPRESS.
AB  - The non-specific background reaction produced in avidin-biotin-based
      immunohistochemistry, particularly after harsh antigen retrieval procedures, has
      promoted the use of non-avidin-biotin systems, yet there are few reports
      comparing the performance of non-avidin-biotin, polymer-based methods. In this
      study we compare two of these methods, ENVISION+trade mark and ImmPRESS, in
      animal tissues. We examined the immunoreactivity of 18 antigens in formalin
      fixed, paraffin-embedded tissues. Antigens were located in the cytoplasmic
      membrane (CD11d, CD18 and CD79a), cytoplasm (calretinin, COX-1, COX-2, Glut-1,
      HepPar 1, KIT, Melan A, tryptase and uroplakin III) or nucleus (MUM-1, PGP 9.5
      and thyroid transcription factor 1). We also evaluated three infectious agents
      (Aspergillus, calicivirus and West Nile virus). The staining with ENVISION+ or
      ImmPRESS was performed simultaneously for each antigen. The intensity of the
      reaction and background staining were scored. ImmPRESS yielded similar or higher
      reaction intensity than ENVISION+trade mark in 16/18 antigens. ImmPRESS produced
      abundant background with the other two antigens (calretinin and COX-2), which
      hindered interpretation of the specific reaction. The cost of ImmPRESS was 25%
      lower than for ENVISION+trade mark. Based on these results, ImmPRESS is a good
      polymer-based detection system for routine immunohistochemistry.

PMID- 17204060
TI  - Application of the focused ion beam technique in aerosol science: detailed
      investigation of selected, airborne particles.
AB  - The focused ion beam technique was used to fabricate transmission electron
      microscope lamellas of selected, micrometre-sized airborne particles. Particles
      were sampled from ambient air on Nuclepore polycarbonate filters and analysed
      with an environmental scanning electron microscope. A large number of particles
      between 0.6 and 10 microm in diameter (projected optical equivalent diameter)
      were detected and analysed using computer-controlled scanning electron
      microscopy. From the resulting dataset, where the chemistry, morphology and
      position of each individual particle are stored, two particles were selected for
      a more detailed investigation. For that purpose, the particle-loaded filter was
      transferred from the environmental scanning electron microscope to the focused
      ion beam, where lamellas of the selected particles were fabricated. The
      definition of a custom coordinate system enabled the relocation of the particles
      after the transfer. The lamellas were finally analysed with an analytical
      transmission electron microscope. Internal structure and elemental distribution
      maps of the interior of the particles provided additional information about the
      particles, which helped to assign the particles to their sources. The combination
      of computer-controlled scanning electron microscopy, focused ion beam and
      transmission electron microscopy offers new possibilities for characterizing
      airborne particles in great detail, eventually enabling a detailed source
      apportionment of specific particles. The particle of interest can be selected
      from a large dataset (e.g. based on chemistry and/or morphology) and then
      investigated in more detail in the transmission electron microscope.

PMID- 17204061
TI  - Long polymeric tips of atomic force microscopy for large biological samples.
AB  - We show a new atomic force microscopy technique for obtaining high-resolution
      topographic images of large bio-samples. To obtain high-resolution topographic
      images for the samples, we fabricated a long polymeric tip with a small
      protrusion using two-photon adsorbed photo-polymerization techniques. The
      obtained tip length was over 50 microm, and the tip was used directly to
      visualize COS-1 and 293 cells. Compared with commercial tips, the long tip made
      it easier to obtain topographic images of the large cells. In the magnified
      topographic images, the sub-100-nm resolution was confirmed with the long tips.
      This long probe tip is expected to broaden large sample-related studies and
      applications in the future.

PMID- 17204062
TI  - Integration of a scanning ion conductance microscope into phase contrast optics
      and its application to the quantification of morphological parameters of selected
      cells.
AB  - We have previously described a pulse-mode scanning ion conductance microscope to
      investigate membrane surfaces and volume changes of individual cells in culture.
      We have now developed a miniaturized scanning headstage that enables us to select
      individual cells for recording under phase contrast optics, considerably
      improving the selection of individual cells for scanning as well as the
      positioning of the scanning frames with respect to the position of the cell
      somata. We show an application in which surfaces and volumes of somata and
      processes of cultured cells from the central nervous system were quantified
      separately.

PMID- 17204063
TI  - Mosaicing of microscope images with global geometric and radiometric corrections.
AB  - Image mosaicing has found a number of applications such as panoramic imaging,
      digital terrain mapping, ophthalmology and virtual microscopy. In this study, we
      present an automated mosaicing technique for generating virtual slides from
      microscope images. We carried out robust image feature matching and global
      geometric and radiometric parameter estimation. The input images were transformed
      using the estimated geometric and radiometric parameters and mosaiced together,
      producing accurate registration of overlapping regions without visible seams.

PMID- 17204064
TI  - Calibration of a wide-field frequency-domain fluorescence lifetime microscopy
      system using light emitting diodes as light sources.
AB  - High brightness light emitting diodes are an inexpensive and versatile light
      source for wide-field frequency-domain fluorescence lifetime imaging microscopy.
      In this paper a full calibration of an LED based fluorescence lifetime imaging
      microscopy system is presented for the first time. A radio-frequency generator
      was used for simultaneous modulation of light emitting diode (LED) intensity and
      the gain of an intensified charge coupled device (CCD) camera. A homodyne
      detection scheme was employed to measure the demodulation and phase shift of the
      emitted fluorescence, from which phase and modulation lifetimes were determined
      at each image pixel. The system was characterized both in terms of its
      sensitivity to measure short lifetimes (500 ps to 4 ns), and its capability to
      distinguish image features with small lifetime differences. Calibration
      measurements were performed in quenched solutions containing Rhodamine 6G dye and
      the results compared to several independent measurements performed with other
      measurement methodologies, including time correlated single photon counting, time
      gated detection, and acousto optical modulator (AOM) based modulation of
      excitation sources. Results are presented from measurements and simulations. The
      effects of limited signal-to-noise ratios, baseline drifts and calibration errors
      are discussed in detail. The implications of limited modulation bandwidth of high
      brightness, large area LED devices ( approximately 40 MHz for devices used here)
      are presented. The results show that phase lifetime measurements are robust down
      to sub ns levels, whereas modulation lifetimes are prone to errors even at large
      signal-to-noise ratios. Strategies for optimizing measurement fidelity are
      discussed. Application of the fluorescence lifetime imaging microscopy system is
      illustrated with examples from studies of molecular mixing in microfluidic
      devices and targeted drug delivery research.

PMID- 17204065
TI  - Nanostructural analysis of starch components by atomic force microscopy.
AB  - Morphological and structural features of starch from potato (Solanum tuberosa)
      and rice (Oryza sativa) have been examined using atomic force microscopy. Amylose
      from potato and rice was observed in aggregated structures, which are suggested
      to be a result of retrogradation during sample preparation. The degrees of
      polymerization of amylose from potato and rice starches were calculated from the
      mean contour lengths of the observed structures to be approximately 1440 and
      1860, respectively. Potato amylopectin appeared as a highly branched and extended
      molecule. Our results show that atomic force microscopy provides a useful method
      for examining the fine structural features and estimating the dimensions of
      starch molecules.

PMID- 17204066
TI  - Determination of mean free path for energy loss and surface oxide film thickness
      using convergent beam electron diffraction and thickness mapping: a case study
      using Si and P91 steel.
AB  - Determining transmission electron microscope specimen thickness is an essential
      prerequisite for carrying out quantitative microscopy. The convergent beam
      electron diffraction method is highly accurate but provides information only on
      the small region being probed and is only applicable to crystalline phases.
      Thickness mapping with an energy filter is rapid, maps an entire field of view
      and can be applied to both crystalline and amorphous phases. However, the
      thickness map is defined in terms of the mean free path for energy loss (lambda),
      which must be known in order to determine the thickness. Convergent beam electron
      diffraction and thickness mapping methods were used to determine lambda for two
      materials, Si and P91 steel. These represent best- and worst-case scenario
      materials, respectively, for this type of investigation, owing to their radically
      different microstructures. The effects of collection angle and the importance of
      dynamical diffraction contrast are also examined. By minimizing diffraction
      contrast effects in thickness maps, reasonably accurate (+/-15%) values of lambda
      were obtained for P91 and accuracies of +/-5% were obtained for Si. The
      correlation between the convergent beam electron diffraction-derived thickness
      and the log intensity ratios from thickness maps also permits estimation of the
      thickness of amorphous layers on the upper and lower surfaces of transmission
      electron microscope specimens. These estimates were evaluated for both Si and P91
      using cross-sectional transmission electron microscopy and were found to be quite
      accurate.

PMID- 17204067
TI  - Investigation of dyed human hair fibres using apertureless near-field scanning
      optical microscopy.
AB  - We present the first studies of dyed human hair fibres performed with an
      apertureless scanning near-field optical microscope. Samples consisted of 5
      microm-thick cross-sections, the hair fibres being bleached and then dyed before
      being cut. Hair dyed with two molecular probes diffusing deep inside the fibre or
      mainly spreading at its periphery were investigated at a wavelength of 655 nm. An
      optical resolution of about 50 nm was achieved, well below the diffraction limit;
      the images exhibited different optical contrasts in the cuticle region, depending
      on the nature of the dye. Our results suggest that the dye that remains confined
      at the hair periphery is mainly located at its surface and in the endocuticle.

PMID- 17204068
TI  - Thermostatic tissue platform for intravital microscopy: 'the hanging drop' model.
AB  - Intravital microscopy imposes the particular problem of the combined control of
      the body temperature of the animal and the local temperature of the observed
      organ or tissues. We constructed and tested, in the rat ileum microcirculation
      preparation, a new organ-support platform. The platform consisted of an organ
      bath filled with physiological solution, and contained a suction tube, a
      superfusion tube, an intestine-support hand that was attached to a
      micromanipulator and a thermometer probe. To cover the intestine we used a cover
      glass plate with a plastic ring glued on its upper surface. After a routine
      procedure (anaesthesia, monitoring and surgery), the intestine segment (2-3 cm
      long) was gently exteriorized and placed on the 'hand' of the organ support. A
      small part of the intestine formed a small 'island' in the bath that was filled
      with physiological salt solution. The cover glass was secured in place. The
      physiological salt solution from the superfusion tube, which was pointed to the
      lower surface of the cover glass, formed a 'hanging drop'. The objective of the
      microscope was then immersed into distilled water that was formed by the cover
      glass plastic ring. The 'hanging drop' technique prevented any tissue quenching,
      ensured undisturbed microcirculation, provided for stable temperature and
      humidity, and permitted a clear visual field.

PMID- 17204069
TI  - Re: Reconstruct: a free editor for serial section microscopy.

PMID- 17204071
TI  - Polyspermy in apomictic Crataegus: yes and no.

PMID- 17204072
TI  - Endosperm formation in aposporous Crataegus (Rosaceae, Spiraeoideae, tribe
      Pyreae): parallels to Ranunculaceae and Poaceae.
AB  - Apomixis in Crataegus is primarily aposporous and requires pollination. The
      embryo sac is of the Polygonum type. A combination of meiotically unreduced
      embryo sacs with apparently reduced pollen would violate the usual requirement
      for a 2 : 1 ratio of maternal to paternal contributions to the endosperm. We
      therefore investigated the origin of endosperm in seeds of sexual diploids and
      apomictic polyploids of the sister genera Crataegus and Mespilus. Flow-cytometric
      DNA measurements from embryo and endosperm in mature seeds were converted to
      ploidy levels using leaf-tissue information. The diploids had triploid endosperm.
      In c. 60% of seed from polyploids, one sperm apparently contributes to the
      endosperm, while 25% or more may involve two sperm. Additional results suggest
      that trinucleate central cells also occur. Fertilization of meiotically unreduced
      eggs is indicated. The ratio of maternal to paternal contributions to the
      endosperm in these apomictic Crataegus is not constrained to 2 : 1. They thus
      resemble some Sorbus (Pyreae) and very distantly related Ranunculus
      (Ranunculaceae). It is suggested that Paspalum (Poaceae) may have similarly
      flexible endosperm ploidy levels.

PMID- 17204073
TI  - Myrmecophilic food body production in the understorey tree, Ryparosa kurrangii
      (Achariaceae), a rare Australian rainforest taxon.
AB  - Plant food bodies are rarely observed in the field, because of continual
      harvesting, and are often first documented on isolated glasshouse plants. Little
      is known about the genus Ryparosa (Achariaceae), and the appearance of outgrowths
      on leaves and stems of glasshouse-raised R. kurrangii seedlings suggested that
      the species may produce food bodies. Detailed macroimaging and histological
      techniques were used to characterize chemomorphological variation in food body
      material gathered from glasshouse plants. Two distinct types of food body were
      observed. Multicellular pearl bodies derived from epidermal and mesophyll tissue
      were produced on young leaves and stems, and contained lipids and glycogen-like
      carbohydrates. A unique form of lipid-rich multicellular food body that 'opens'
      during development was found exclusively on mature plant tissue. A filament
      network was associated with food body lipid droplets. This is the first detailed
      documentation of food body production in an understorey genus adapted to low
      light conditions. We suggest that the distinctive spatial deployment of Ryparosa
      food rewards, and the ants attracted to them, may be invaluable for keeping long
      lived leaves free from epiphyllous communities.

PMID- 17204074
TI  - Apoplastic barriers to radial oxygen loss and solute penetration: a chemical and
      functional comparison of the exodermis of two wetland species, Phragmites
      australis and Glyceria maxima.
AB  - Few studies have examined exodermal development in relation to the formation of
      barriers to both radial oxygen loss (ROL) and solute penetration along growing
      roots. Here, we report on the structural development, chemical composition and
      functional properties of the exodermis in two diverse wetland grasses, Glyceria
      maxima and Phragmites australis. Anatomical features, development, the
      biochemical composition of exodermal suberin and the penetration of apoplastic
      tracers and oxygen were examined. Striking interspecific differences in exodermal
      structure, suberin composition and quantity per unit surface area, and
      developmental changes along the roots were recorded. Towards the root base, ROL
      and periodic acid (H(5)IO(6)) penetration were virtually stopped in P. australis;
      in G. maxima, a tight ROL barrier restricted but did not stop H(5)IO(6)
      penetration and the exodermis failed to stain with lipidic dyes. Cultivation in
      stagnant deep hypoxia conditions or oxygenated circulating solution affected the
      longitudinal pattern of ROL profiles in G. maxima but statistically significant
      changes in exodermal suberin composition or content were not detected.
      Interspecific differences in barrier performance were found to be related to
      hypodermal structure and probably to qualitative as well as quantitative
      variations in suberin composition and distribution within exodermal cell walls.
      Implications for root system function are discussed, and it is emphasized that
      sufficient spatial resolution to identify the effects of developmental changes
      along roots is crucial for realistic evaluation of exodermal barrier properties.

PMID- 17204075
TI  - Nitrogen uptake and metabolism in Populus x canescens as affected by salinity.
AB  - External salinization can affect different steps of nitrogen (N) metabolism (ion
      uptake, N assimilation, and amino acid and protein synthesis) depending on the
      inorganic N source. Here, we assessed the net uptake of N supplied as nitrate or
      ammonium and N assimilation (combining metabolite analyses with molecular
      biological approaches) in grey poplar (Populus x canescens) plants grown under
      saline (75 mM NaCl) and control conditions. The specific (micromol N g(-1) dry
      weight fine roots h(-1)) and total plant (micromol N per plant h(-1)) N net
      uptake rates, total plant N content, total plant biomass and total leaf protein
      concentration were reduced under saline conditions when plants were supplied with
      ammonium. In both nutritional groups, salt treatment caused pronounced
      accumulation of soluble N compounds in the leaves. The mRNAs of genes coding for
      enzymes catalyzing rate-limiting steps of both proline synthesis and degradation
      (delta-1-pyrroline-5-carboxylate synthase and proline dehydrogenase) as well as
      for NADH-dependent glutamate synthase were accumulated under saline conditions.
      Whereas under control conditions the plant N status seemed to be superior when
      ammonium was supplied, the N balance of ammonium-fed plants was more severely
      affected by salt stress than that of plants supplied with nitrate. Possible
      metabolic implications of stress-related accumulation of particular amino acids
      are discussed.

PMID- 17204076
TI  - Large variation in whole-plant water-use efficiency among tropical tree species.
AB  - It is well known that whole-plant water-use efficiency (transpiration efficiency
      of carbon gain, TE(C)) varies among plant species with different photosynthetic
      pathways. However, less is known of such variation among tree species within the
      C(3) group. Here we measured the TE(C) of seven C(3) tropical tree species.
      Isotopic analyses (delta(13)C, delta(18)O, and delta(15)N) and elemental analyses
      (carbon and nitrogen) were undertaken to provide insight into sources of
      variation in TE(C). Plants were grown over several months in approx. 80% full
      sunlight in individual 38-l containers in the Republic of Panama. Soil moisture
      content was nonlimiting. Significant variation was observed in TE(C) among the
      C(3) tree species. Values ranged from 1.6 mmol C mol(-1) H(2)O for teak (Tectona
      grandis) to 4.0 mmol C mol(-1) H(2)O for a legume, Platymiscium pinnatum.
      Variation in TE(C) was correlated with both leaf N concentration, a proxy for
      photosynthetic capacity, and oxygen-isotope enrichment, a proxy for stomatal
      conductance. The TE(C) varied with C-isotope discrimination within species, but
      the relationship broke down among species, reflecting the existence of species
      specific offsets.

PMID- 17204077
TI  - Are correlations among foliar traits in ferns consistent with those in the seed
      plants?
AB  - Broad-based studies of gymnosperms and angiosperms reveal consistent and
      functionally significant correlations among foliar traits such as leaf mass per
      area (LMA), maximum photosynthetic rate (A(area)), foliar nitrogen (N(area)),
      foliar chlorophyll (Chl) and leaf longevity. To assess the generality of these
      relationships, we studied 20 fern species growing in the understorey of a
      temperate deciduous forest. We found that foliar N(area) increases with LMA, and
      that foliar N(area) and A(area) are positively correlated with one another, as
      are foliar N(area) and Chl. The ferns in general have very low LMA compared with
      most seed plants; A(area), N(area) and Chl are below median values for seed
      plants but are not extreme. Species with overwintering fronds have significantly
      higher LMA than species with fronds that senesce at the end of the growing
      season, as well as a significantly higher C : N ratio in frond tissue and
      relatively high foliar N on an areal basis. Correlations among foliar traits
      associated with gas exchange in these forest understorey ferns are in accordance
      with patterns reported for seed plants, suggesting a high degree of functional
      constraint on the interrelationships among key elements in foliar design.

PMID- 17204078
TI  - Relating root structure and anatomy to whole-plant functioning in 14 herbaceous
      Mediterranean species.
AB  - This study investigated the relationships between root structure and anatomy and
      whole-plant functioning in herbaceous species. Fourteen annual and perennial
      species representative of a Mediterranean old-field succession were grown in
      monocultures in a common-garden experiment. Whole-plant functioning was assessed
      by inherent relative growth rate (RGR(max)), measured in standardized conditions,
      and maximum height (H(max)). Root tissue density (TMD(r)), considered as a major
      component of root structure, was measured on roots harvested within in-growth
      cores. Anatomical characteristics were analysed on cross-sectional areas (CSA).
      TMD(r) was correlated positively with H(max) and negatively with RGR(max). Root
      CSA explained interspecific variation in H(max) but not that in TMD(r) and
      RGR(max). Root xylem CSA and xylem proportion in root CSA were positively
      correlated with TMD(r) and H(max) and negatively with RGR(max). Mean xylem vessel
      CSA did not account for variations in TMD(r), H(max) and RGR(max). These results
      suggested that RGR(max) and H(max) are constrained by opposite root structural
      and anatomical traits, which have potential links with hydraulic conductance,
      support and longevity.

PMID- 17204079
TI  - Does ectomycorrhizal fungal community structure vary along a Japanese black pine
      (Pinus thunbergii) to black locust (Robinia pseudoacacia) gradient?
AB  - In this study we examined the role of the nitrogen-fixing tree, Robinia
      pseudoacacia (black locust), in ectomycorrhizal (ECM) formation and ECM community
      of Pinus thunbergii (Japanese black pine) seedlings. Two 200 m(2) experimental
      plots were established at the border between a Japanese black pine- and a black
      locust-dominated area in a coastal forest. The ECM fungal community of pine
      seedlings was examined by PCR-RFLP and sequence analysis. We analyzed the
      relationship between ECM formation, ECM community, growth, and nutrient status of
      pine seedlings and environmental conditions using the Mantel test and structural
      equation model. Percentages of ECM root tips, the number of ECM fungal species
      and ECM diversity on pine seedlings decreased in the black locust-dominated area.
      Cenococcum geophilum and Russula spp. were dominant in the Japanese black pine
      dominated area, whereas Tomentella spp. were dominant in the black locust
      dominated area. Nitrogen (N) concentration in soils or pine seedlings strongly
      influenced the percentage of ECM root tips, the number of ECM fungal species and
      ECM fungal similarity. These results imply the long-term eutrophication caused by
      N-fixing trees can change ECM formation and ECM community structure.

PMID- 17204080
TI  - Bypassing of a polygenic Microcyclus ulei resistance in rubber tree, analyzed by
      QTL detection.
AB  - Genetic resistance components of the Hevea brasiliensis x H. benthamiana RO 38
      cultivar to Microcyclus ulei disease were investigated by inoculating isolates
      which succeeded in partially or completely infecting genotypes of a mapping
      population. Progeny of a cross between RO 38 and a susceptible cultivar was
      inoculated under controlled conditions with three isolates and scored for two
      resistance traits. Interval mapping and a nonparametric test were used to detect
      resistance quantitative trait loci (QTLs). Eight significant QTLs were detected,
      all of them inherited from the interspecific parent. Among these QTLs, only one
      contributed to the partial resistance against a highly pathogenic isolate, and no
      QTL was detected for resistance against the most pathogenic isolate. As an
      unexpected result, a single isolate can thus completely bypass this polygenic
      resistance. This complex situation, where no clear relationship can be
      established between number of resistance factors and qualitative vs quantitative
      or partial vs complete resistance, is discussed and suggestions as to the
      detection of new and sustainable resistance sources are proposed.

PMID- 17204081
TI  - Dramatic reduction of crop-to-crop gene flow within a short distance from
      transgenic rice fields.
AB  - Genetically modified (GM) rice with enhanced agronomic traits and pharmaceutical
      uses are ready for widespread adoption. Little is known about isolation
      requirements for achieving stringent transgene confinement in rice. To
      investigate the extent of pollen-mediated crop-to-crop transgene flow, we
      conducted a field experiment with four plot-size treatments of adjacent GM and
      nonGM rice (Oryza sativa) in China. Three insect-resistant GM rice (Bt/CpTI) and
      nonGM isogenic lines were used in the study. The hygromycin-resistance transgene
      (hpt) marker was used to screen seeds from the nonGM rice rows at different
      distance intervals from GM rice plots. Based on the examination of > 2.1 million
      germinated seeds, we found a dramatic reduction in transgene frequencies with
      increasing distance from the GM crop, ranging from c. 0.28% at 0.2 m to < 0.01%
      at 6.2 m. In addition, different plot size did not significantly affect the
      frequencies of gene flow. In conclusion, pollen-mediated crop-to-crop transgene
      flow in rice can be maintained at negligible levels with short spatial isolation.
      The model can also be applied to other crops with self- and wind-pollination.

PMID- 17204082
TI  - Collinsia sparsiflora in serpentine and nonserpentine habitats: using F2 hybrids
      to detect the potential role of selection in ecotypic differentiation.
AB  - Here we document phenotypic differences between serpentine and nonserpentine
      ecotypes of Collinsia sparsiflora, as well as patterns of selection in these
      contrasting soil habitats. We transplanted the two parental ecotypes and
      experimental F2 hybrids into six field sites, and collected morphological,
      phenological and fitness data on emergent plants. To focus on edaphically
      mediated selection, rather than on pollinator-mediated selection, we used
      pollinator-exclusion cages. Transplanted parentals of the two ecotypes showed
      genetic differentiation for floral traits, but not for phenological traits or
      cotyledon size. For the F2 hybrids growing on serpentine soils, there was
      significant directional selection on cotyledon size, flower size and flower
      shape. However, the pattern of selection did not differ significantly between
      serpentine and nonserpentine sites. Overall, we did not see evidence for
      divergent selection on the two soil types. We conclude that differences in floral
      traits between the ecotypes do not reflect adaptation to physical conditions
      associated with soil type, and that there are unmeasured traits that must be
      contributing to ecotypic differentiation.

PMID- 17204083
TI  - Reproductive limits of a late-flowering high-mountain Mediterranean plant along
      an elevational climate gradient.
AB  - Mountain plants are particularly sensitive to climate warming because snowmelt
      timing exerts a direct control on their reproduction. Current warming is leading
      to earlier snowmelt dates and longer snow-free periods. Our hypothesis is that
      high-mountain Mediterranean plants are not able to take advantage of a lengthened
      snow-free period because this leads to longer drought that truncates the growing
      season. However, reproductive timing may somewhat mitigate these negative effects
      through temporal shifts. We assessed the effects of flowering phenology on the
      reproductive success of Silene ciliata, a Mediterranean high-mountain plant,
      across an altitudinal gradient during two climatically contrasting years. The
      species showed a late-flowering pattern hampering the use of snowmelt water.
      Plant fitness was largely explained by the elapsed time from snowmelt to onset of
      flowering, suggesting a selective pressure towards early flowering caused by soil
      moisture depletion. The proportion of flowering plants decreased at the lowest
      population, especially in the drier year. Plants produced more flowers, fruits
      and seeds at the highest population and in the mild year. Our results indicate
      that water deficit in dry years could threaten the lowland populations of this
      mountainous species, while high-altitude environments are more stable over time.

PMID- 17204084
TI  - Inbreeding depression in an autotetraploid herb: a three cohort field study.
AB  - Autotetraploids are predicted to have reduced inbreeding depression relative to
      diploids. However, recent theory and information on genomic changes following
      autopolyploidy suggest that inbreeding depression may be closer to diploids. In
      three consecutive years, self and outcross pollinations were conducted on
      autotetraploid Campanulastrum americanum, seeds were planted into native sites,
      and biennial offspring were followed through seed production. Inbred individuals
      had lower germination rates, reduced survival, were smaller, and flowered later,
      producing fewer fruits with fewer seeds. Inbred offspring had 6% of the
      cumulative fitness of outcross offspring. Although performance varied
      substantially among cohorts, inbreeding depression for cumulative fitness was
      relatively constant, with delta ranging only from 0.92 to 0.95. C. americanum,
      like many outcrossing species, expressed very high amounts of inbreeding
      depression. This supports the hypothesis that inbreeding depression of some
      autotetraploids may be similar to that of diploids. Furthermore, few studies have
      measured temporal variation in inbreeding depression. Constant inbreeding
      depression given a sixfold range in cohort performance suggests that inbreeding
      depression may be relatively robust to environmental variation experienced by
      natural populations.

PMID- 17204085
TI  - Microgametophyte population sizes and plant reproductive output in the insect
      pollinated Prunella grandiflora (Lamiaceae).
AB  - Intraspecific variation in pollen deposition and number of pollen tubes per style
      is rarely quantified, but is essential for assessing the occurrence of pollen
      limitation and pollen competition and their evolutionary implications. Moreover,
      pollen deposition, pollen tube growth, and the fate of fertilized ovules are
      rarely distinguished in field studies. Here we present such a study in eight
      natural populations of Prunella grandiflora. We quantified microgametophyte
      population sizes and inferred pollen limitation when the number of fertilizable
      ovules exceeded pollen tubes, and assessed seed set and fate after open
      pollination. Two and three populations had on average significantly fewer pollen
      grains and pollen tubes per flower, respectively, than the fixed number of
      fertilizable ovules per fruit, while one population experienced significant
      pollen competition. Style length was positively correlated with the number of
      pollen tubes. While pollen availability was very variable, seed abortion was
      significantly less frequent in denser populations, and in one population the
      proportion of well-developed seeds was significantly, positively correlated with
      the number of pollen tubes in the style. Less pollen deposition, lower numbers of
      pollen tubes reaching the base of the style, lower pollen quality and therefore
      increased abortion of fertilized ovules can all reduce seed set in natural P.
      grandiflora stands. Substantial intraspecific variability implies that
      microgametophyte competition also occurs in this species. Finally, style
      morphology may affect pollen receipt.

PMID- 17204086
TI  - Macrophylogenetic analyses of the gain and loss of self-incompatibility in the
      Asteraceae.
AB  - The self-incompatibility (SI) status of 571 taxa from the Asteraceae was
      identified and the taxa were scored as having SI, partial SI or self
      compatibility (SC) as their breeding system. A molecular phylogeny of the
      internal transcribed spacer (ITS) region was constructed for 211 of these taxa.
      Macrophylogenetic methods were used to test hypotheses concerning the ancestral
      state of SI in the Asteraceae, the gain and loss of SI, the irreversibility of
      the loss of SI and the potential for partial SI or SC to be terminal states. The
      ancestral breeding system in the family could not be resolved. Both maximum
      likelihood and parsimony analyses indicated that transitions among all breeding
      system states provide the best fit to the data and that neither partial SI nor SC
      is a terminal state. Furthermore, the data indicated that the loss of SI is not
      irreversible, although breeding system evolution has been more dynamic in some
      clades than in others. These results are discussed within the context of evidence
      for the gain and loss of SI, the evolutionary role of partial SI and
      methodological assumptions of tests of breeding system evolution.

PMID- 17204087
TI  - Correlated evolution of self-incompatibility and clonal reproduction in Solanum
      (Solanaceae).
AB  - It has been suggested that clonality provides reproductive assurance in cross
      fertilizing species subject to pollen limitation, relieving one of the main
      selective pressures favoring the evolution of self-fertilization. According to
      this hypothesis, cross-fertilizing species subject to pollen limitation should
      often be clonal. Here, we investigated the association between clonality and a
      genetic mechanism enforcing outcrossing, self-incompatibility, in Solanum
      (Solanaceae). We collected self-incompatibility and clonality information on 87
      species, and looked for an association between these two traits. To account for
      the contribution of shared evolutionary history to this association, we
      incorporated phylogenetic information from chloroplast (NADH dehydrogenase
      subunit F) sequence data. We found that self-incompatibility is strongly
      associated with clonal reproduction: all self-incompatible species reproduce
      clonally, while the absence of clonality is widespread among self-compatible
      taxa. The observed correlation persists after taking into account shared
      phylogenetic history, assumptions about the evolutionary history of self
      incompatibility, uncertainty associated with phylogeny estimation, and
      associations with life history (annual/perennial). Our results are consistent
      with the hypothesis that clonality provides reproductive assurance, and suggest
      that the consequences of clonal growth in the evolution of plant reproductive
      strategies may be more significant than previously thought.

PMID- 17204088
TI  - Correlated evolution of genome size and seed mass.
AB  - Previous investigators have identified strong positive relationships between
      genome size and seed mass within species, and across species from the same genus
      and family. Here, we make the first broad-scale quantification of this
      relationship, using data for 1222 species, from 139 families and 48 orders. We
      analyzed the relationship between genome size and seed mass using a statistical
      framework that included four different tests. A quadratic relationship between
      genome size and seed mass appeared to be driven by the large genome/seed mass
      gymnosperms and the many small genome size/large seed mass angiosperms. Very
      small seeds were never associated with very large genomes, possibly indicating a
      developmental constraint. Independent contrast results showed that divergences in
      genome size were positively correlated with divergences in seed mass. Divergences
      in seed mass have been more closely correlated with divergences in genome size
      than with divergences in other morphological and ecological variables. Plant
      growth form is the only variable examined thus far that explains a greater
      proportion of variation in seed mass than does genome size.

PMID- 17204089
TI  - Localization of water-soluble carbohydrates in wheat stems using imaging matrix
      assisted laser desorption ionization mass spectrometry.
AB  - The pool of endogenous water-soluble oligosaccharides found in the stems of wheat
      (Triticum aestivum) is being investigated as a potential indicator of grain
      yield. Techniques such as liquid chromatography with mass spectrometry (LC-MS)
      can profile these analytes but provide no spatial information regarding their
      distribution in the wheat stem. The imaging matrix-assisted laser desorption
      ionization (MALDI) mass spectrometry technique has not been utilized for the
      analysis of oligosaccharides in plant systems previously. Imaging MALDI mass
      spectrometry was used to analyse cross and longitudinal sections from the stems
      of Triticum aestivum. A range of oligosaccharides up to Hex(11) were observed.
      Water-soluble oligosaccharides were ionized as potassiated molecules, and found
      to be located in the stem pith that is retained predominantly around the inner
      stem wall. Imaging MALDI analyses provided spatial information on endogenous
      oligosaccharides present in wheat stems. The technique was found to offer
      comparable sensitivities for oligosaccharide detection to those of our
      established LC-MS method, and has potential for broad application in studying the
      in situ localization of other compound types in plant material.

PMID- 17204091
TI  - Expression of SpanX mRNA in testicular germ cell tumors.
AB  - The function of SpanX proteins is unknown, evidence is accumulating to suggest
      their involvement in tumorigenesis. A locus in Xq27, where the SpanX gene family
      is located, has been associated with testicular germ cell tumor (TGCT) onset.
      Therefore, we evaluated the presence of SpanX mRNA in six TGCT cases by RT-PCR.
      The results showed that SpanX mRNA is present in TGCT, confirming transcriptional
      activity of these genes in such tumors.

PMID- 17204092
TI  - Expression of hepatocyte growth factor activator inhibitor type 1 in endothelial
      cells.
AB  - Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is an integral
      membrane Kunitz-type serine proteinase inhibitor initially identified as a potent
      inhibitor of hepatocyte growth factor activator (HGFA). HGFA is a serum
      proteinase that is critically involved in the activation of hepatocyte growth
      factor/scatter factor (HGF/SF) in injured tissue. Previous studies have shown
      that HAI-1 is expressed on the basolateral surface of various epithelial cells.
      In this study, we analyzed the expression of HAI-1 in human endothelial cells.
      Immunohistochemically, HAI-1 protein was observed in the endothelial cells of
      capillaries, venules and lymph vessels. On the other hand, arterial endothelial
      cells were poorly stained for HAI-1. Mesothelial cells on the serous surface were
      also positively immunostained. The endothelial expression of HAI-1 was also
      examined in cultured human endothelial cells of various origins, such as
      umbilical vein, microvessels and aorta. Notably, in accordance with the results
      of immunohistochemistry, HAI-1 mRNA and protein levels were high in the
      endothelial cells derived from umbilical vein and were hardly detectable in those
      derived from aorta. A low but distinct level of HAI-1 expression was also
      observed in endothelial cells from microvessels. As these HAI-1-positive
      endothelial cells also expressed MET tyrosine kinase, the specific receptor of
      HGF/SF, it is conceivable that HAI-1 might have an important regulatory role in
      the HGF/SF-MET signaling axis of endothelial cells, which could be involved in
      the process of angiogenesis.

PMID- 17204094
TI  - Anti-p200 pemphigoid: a novel autoimmune subepidermal blistering disease.
AB  - Anti-p200 pemphigoid is a recently defined autoimmune subepidermal blistering
      disease characterized by circulating and tissue-bound autoantibodies to a 200-kDa
      protein (p200) of the dermal-epidermal junction (DEJ). This DEJ constituent is
      thought to be important for adhesion of basal keratinocytes to the underlying
      dermis. While the exact identity of p200 remains unknown, it has been
      demonstrated to be immunologically and biochemically distinct from all major
      autoantigens of the DEJ, including bullous pemphigoid antigens 180 and 230,
      laminin 1, 5 and 6, alpha6beta4 integrin, and type VII collagen. Clinically, most
      reported cases present with tense blisters as well as urticarial papules and
      plaques, closely resembling bullous pemphigoid. Histopathological examination of
      lesional skin biopsies shows subepidermal split formation and superficial
      inflammatory infiltrate typically dominated by neutrophils. Immunopathologically,
      linear deposits of immunoglobulin (Ig)G and C3 are detected along the DEJ by
      direct immunofluorescence microscopy of perilesional skin. Indirect
      immunofluorescence microscopy of patients' sera on NaCl-split human skin
      demonstrates circulating IgG autoantibodies labeling the dermal side of the
      split. By immunoblotting, these autoantibodies recognize a 200-kDa protein of
      human dermis. Biochemical characterization of the p200 molecule revealed a
      noncollagenous N-glycosylated acidic protein with an isoelectric point of
      approximately 5.5. We present an overview of the pathogenesis, clinical features,
      diagnosis and treatment of this new disease entity.

PMID- 17204093
TI  - Global gene expression profiling of preimplantation embryos.
AB  - Preimplantation development is marked by four major events: the transition of
      maternal transcripts to zygotic transcripts, compaction, the first lineage
      differentiation into inner cell mass and trophectoderm, and implantation. The
      scarcity of the materials of preimplantation embryos, both in size (diameter <
      100 microm) and in quantity (only a few to tens of oocytes from each ovulation),
      has hampered molecular analysis of preimplantation embryos. Recent progress in
      RNA amplification methods and microarray platforms, including genes unique to
      preimplantation embryos, allow us to apply global gene expression profiling to
      the study of preimplantation embryos. Our gene expression profiling during
      preimplantation development revealed the distinctive patterns of maternal RNA
      degradation and embryonic gene activation, including two major transient waves of
      de novo transcription. The first wave corresponds to zygotic genome activation
      (ZGA). The second wave, mid-preimplantation gene activation (MGA), contributes
      dramatic morphological changes during late preimplantation development. Further
      expression profiling of embryos treated with inhibitors of transcription or
      translation revealed that the translation of maternal RNA is required for the
      initiation of ZGA, suggesting a cascade of gene activation from maternal
      RNA/protein sets to ZGA gene sets and thence to MGA gene sets. To date, several
      reports of microarray experiments using mouse and human preimplantation embryos
      have been published. The identification of a large number of genes and multiple
      signaling pathways involved at each developmental stage by such global gene
      expression profiling accelerates understanding of molecular mechanisms
      underlining totipotency/pluripotency and programs of early mammalian development.

PMID- 17204095
TI  - Effect of standard medication on quality of life of patients with atopic
      dermatitis.
AB  - Patients with atopic dermatitis present with debilitating symptoms, including
      pruritus and subsequent excoriation, which significantly reduces their quality of
      life (QOL). At present, the standard therapy for atopic dermatitis constitutes a
      topical steroid and/or a topical immunomodulator, an emollient and an oral
      antihistamine, although few studies have reported the effect of this treatment
      regimen on QOL. The current study aimed to verify the efficacy of the standard
      therapy for both clinical symptom severity and patient QOL, assessed using the
      validated Skindex-16 questionnaire. Atopic dermatitis patients receiving the
      standard therapy (n=771) were enrolled in the current phase IV, multicenter, 12
      week, open-label study. The Rajka and Langeland scale (used to rate the severity
      of atopic dermatitis symptoms) and the Skindex-16 QOL questionnaire were
      completed at weeks 0 (baseline), 4 and 12. Of 415 patients completing the
      questionnaire at all time points (per-protocol population), 95.2% were prescribed
      the antihistamine fexofenadine HCl 60 mg. There were significant improvements in
      symptoms, emotions and functioning scale scores at weeks 4 and 12 compared with
      baseline (P<0.005). Discomfort associated with itching, as assessed by item 1 on
      the Skindex-16, improved over the treatment period (score decreased by >or=1 and
      >or=2 in 75.2% and 50.9% of patients, respectively). Significant (P<0.005)
      improvements from baseline in global scores were also observed at weeks 4 and 12,
      and for week 12 compared with week 4. Severity scores improved significantly
      (P<0.005) from weeks 0-4 and from weeks 4-12. The standard therapy was generally
      well tolerated with only mild adverse events reported (0.5%). These data suggest
      that patients with atopic dermatitis and associated pruritus experience
      significant improvements in both symptom severity and QOL when receiving standard
      therapy.

PMID- 17204096
TI  - Effectiveness of modified phenol peel (Exoderm) on facial wrinkles, acne scars
      and other skin problems of Asian patients.
AB  - Deep depth peeling using phenol is one of the most effective chemical peeling
      methods. However, it has been rarely used on Asian people because of side
      effects, especially hypopigmentation. In order to reduce side-effects, a number
      of modified phenol peeling formulas were developed. Exoderm, a modified phenol
      peel, has shown reduced side-effects such as arrhythmia, long-lasting erythema,
      hypopigmentation, hypertrophic scar and keloid. In the present study, our aim was
      to evaluate the effectiveness of Exoderm on wrinkles, acne scars, and melasma and
      its safety for Asian patients. Forty-six patients were treated with Exoderm.
      Twenty-eight patients (61%) were treated for wrinkles and 11 patients (24%) for
      acne scars. Clinical improvement and side-effects were evaluated and the degree
      of improvement was graded into four stages. The overall average improvement
      scores were 3.39 and 3.30 out of 4.00 as evaluated by the doctor and patient,
      respectively. Forty-one patients (89%) showed 51% or more improvement. All
      patients with wrinkles improved 51% or more and their average improvement score
      was 3.64 out of 4.00. Seven of 11 patients (64%) with acne scars improved 51% or
      more and their average improvement score was 2.73 out of 4.00. The most frequent
      side-effect was postinflammatory hyperpigmentation (74%). Prolonged erythema,
      keloid and milia were observed temporarily, however, hypopigmentation persisted
      for 6 months in the follow-up period. All side-effects were tolerable and
      reversible except for one complication of hypopigmentation. We conclude that
      Exoderm is very effective for treating the facial wrinkles and acne scars of
      Asian patients.

PMID- 17204097
TI  - Efficacy and safety of serial glycolic acid peels and a topical regimen in the
      treatment of recalcitrant melasma.
AB  - Melasma is a common acquired disorder of facial hyperpigmentation. In this study
      we investigated the efficacy and safety of a combined treatment regimen including
      serial glycolic acid peels, topical azelaic acid cream and adapalene gel in the
      treatment of recalcitrant melasma. Twenty-eight patients with recalcitrant
      melasma were enrolled in a prospective, randomized, controlled trial lasting 20
      weeks. The patients of the group receiving chemical peels underwent serial
      glycolic acid peels in combination with topical azelaic acid 20% cream (b.i.d.)
      and adapalene 0.1% gel (q.i.d., applied at night). The control group received
      only topical treatment including topical azelaic acid and adapalene. The clinical
      improvement was assessed with the Melasma Area Severity Index (MASI) at baseline
      and monthly during the 20-week treatment period. The results showed a prominent
      decrease in MASI scores at the end of the treatment in both groups, although the
      results were better in the group receiving chemical peels (P=0.048). All patients
      tolerated the topical agents well with minimal irritation observed in the first
      few weeks of the therapy. Three patients in the glycolic acid peel group
      developed a mild-degree postinflammatory hyperpigmentation with total clearance
      at the end of the treatment period. Therefore, the present study suggests that
      combined treatment with serial glycolic acid peels, azelaic acid cream and
      adapalene gel should be considered as an effective and safe therapy in
      recalcitrant melasma.

PMID- 17204098
TI  - Prediction of metastases in melanoma patients with positive sentinel node:
      histological and molecular approach.
AB  - It is now established that sentinel node (SN) biopsy is a minimally-invasive
      procedure that accurately indicates the regional nodal status. In our institute,
      14 consecutive patients had only one node micrometastases after elective lymph
      node dissection or positive SN for primary cutaneous melanoma. These 14 patients
      could be clearly divided into two groups: (i) patients who developed distant
      metastases or in-transit metastases (metastasized group); and (ii) and patients
      who remains free from metastases (non-metastasized group). The purpose of this
      study was to identify the histological and molecular factors that might predict
      the further dissemination beyond the SN. We assessed the maximum depth from the
      capsule to the deepest melanoma cells and the maximum diameter of melanoma nests
      in the lymph nodes as histological parameters and also evaluated the quantitative
      expression of tyrosinase mRNA as a molecular approach. The mean maximum depth and
      the maximum diameter were significantly smaller in the metastasized group than
      those in the non-metastasized group. Tyrosinase mRNA expression was strongly
      correlated with the histological tumor burden. Tyrosinase mRNA expression was
      higher in the former group than that in the latter group but there were no
      significant differences between them. Melanoma patients with small
      micrometastases (<0.5 mm deep, <1 mm in diameter) and a low level of tyrosinase
      mRNA had less chances for hematogenous metastases via lymph nodes.

PMID- 17204099
TI  - Topical 5-aminolaevulinic acid photodynamic therapy for intractable palmoplantar
      psoriasis.
AB  - Photodynamic therapy (PDT) has been reported to be useful in treating non
      melanoma skin cancers and a variety of benign skin conditions including
      psoriasis. However, only two reports of palmoplantar pustular psoriasis (PPP)
      treated with PDT have been reported. We treated three intractable cases of PPP
      with PDT, using 20% 5-aminolaevulinic acid and a 630+/-50 nm light-emitting diode
      device. The power density was 30 mW/cm2 and the fluence was 15 J/cm2. After
      treatment, all cases showed mild to marked improvement. Topical PDT may be an
      alternative therapy in the treatment of PPP, but further study is necessary to
      confirm the effectiveness of topical PDT in PPP.

PMID- 17204100
TI  - Case of keratosis lichenoides chronica with atypical sarcoidal granulomatous
      inflammation.
AB  - Keratosis lichenoides chronica (KLC) is a rare chronic disease characterized by
      violaceous, papular and nodular lesions typically arranged in a linear and
      reticulate pattern. The etiology of KLC is unknown, but it may be associated with
      internal diseases such as hypothyroidism, glomerulonephritis and
      lymphoproliferative disorders. Herein, we describe the case of 44-year-old male
      patient with characteristic lesions of KLC on the trunk and extremities, present
      for 12 years. The clinical diagnosis was proven by histopathological examination
      on several occasions. In the years following the diagnosis of KLC, he developed
      bilateral hilar and multiple mediastinal, cervical and inguinal lymphadenopathies
      and hepatosplenomegaly. In 2000, diffuse interstitial and then reticulonodular
      pulmonary infiltrates associated with fever, weight loss, malaise and
      subcutaneous nodules developed. Biopsies taken from peripheral and mediastinal
      lymph nodes, pulmonary parenchyma, pleural tissue, bone marrow and skin showed
      non-necrotizing granulomas, indicating a sarcoidal granulomatous reaction.
      Characteristic histopathological findings and the absence of atypical cells,
      clonality and a high proliferative index excluded lymphomas. Furthermore,
      detailed tests showed no evidence of an infectious granulomatous disease. As far
      as we know, this is the first reported case of KLC associated with a sarcoidal
      granulomatous reaction.

PMID- 17204101
TI  - Case of metastatic melanoma in an epitrochlear lymph node arising in a pregnant
      woman.
AB  - We describe a rare case of metastatic melanoma in an epitrochlear lymph node in a
      29-year-old female patient. The patient had been aware of a brown macule on her
      right posterior forearm at puberty. Because the lesion had enlarged rapidly, she
      was referred to our hospital. Histological examination revealed a malignant
      melanoma. She underwent wide local excision with 3-cm margins and split thickness
      skin graft closure, but we were not able to perform sentinel node biopsy. She
      also received three cycles of systemic chemotherapy with dacarbazine, nimustine,
      vincristine and interferon-beta. However, an epitrochlear node (interval node)
      metastasis occurred during pregnancy (seventh week) 2 years after the operation.
      We emphasize that it is important for clinicians to pay attention to the
      possibility of epitrochlear node metastasis in patients with malignant melanoma
      in the upper extremity and that it is necessary to perform sentinel node biopsy
      to identify uncommon lymph node metastasis.

PMID- 17204102
TI  - Melanocytic nevi clinically simulating melanoma.
AB  - Melanoma and other benign or malignant pigmented skin tumors can significantly
      overlap in their clinical and dermoscopical presentations. Thus, pigmented skin
      lesions may be misdiagnosed in a large number of cases. An extensive review of
      the published work provides numerous examples of benign lesions mimicking
      melanoma. Although a number of melanocytic nevi may have been identified as
      melanomas, information about their clinical appearance is limited. In this
      report, we present the clinical appearances of two melanocytic nevi on the vulva
      and the upper extremity that were difficult to diagnose clinically. Detecting
      melanoma at an early stage is of the utmost importance. However, more attention
      should be given to the diagnostic accuracy of benign pigmented skin lesions,
      which otherwise may be diagnosed and treated as melanoma.

PMID- 17204103
TI  - Atypical melanosis of the foot showing a dermoscopic feature of the parallel
      ridge pattern.
AB  - A 62-year-old male Turkish patient had a pigmented lesion on the sole with a 10
      year history. It was an asymmetrical macular lesion with an irregular border and
      irregular brown pigmentation and had a diameter of 1.2 cm x 1.7 cm. Dermoscopy
      revealed a parallel ridge pattern and an abrupt cut-off of pigmentation on the
      upper edge. Histologically lentiginous hyperplasia decorated by innocent
      melanocytes and scattered melanocytic proliferation with slight to moderate
      cytological atypia were seen. Atypical melanocytes were very scattered and it was
      insufficient to call it a melanoma in situ. A second finding was a microvascular
      proliferation located in the papillary dermis. There was no sign of regression
      such as fibrous tissue or host reaction. Atypical melanosis of the foot has
      rarely been reported in the published work, which are from Japan and Korea. This
      case is presented to emphasize the significance of this rare entity which has
      recently been reported to be a very early phase of acral melanoma.

PMID- 17204104
TI  - Neurofibromatosis type 2 in an infant with multiple plexiform schwannomas as
      first symptom.
AB  - Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder that is caused
      by inactivating mutations or a loss of both alleles in the NF2 tumor-suppressor
      gene. Bilateral vestibular schwannomas are considered to be the hallmark of this
      disease, with hearing loss and tinnitus which are caused by these tumors, usually
      presenting as the initial symptoms. In addition to other tumors and ocular
      findings, skin abnormalities also occur in NF2, however, they are not so
      characteristic as neurofibromatosis type 1 (NF1). We herein report a case of NF2
      which occurred in a 5-year-old boy. He had multiple cutaneous tumors but did not
      have any symptoms related to vestibular schwannomas. He also had multiple
      depigmented spots. A histopathological examination revealed these tumors to be
      plexiform schwannomas; we therefore suspected NF2. As a result of magnetic
      resonance imaging with gadolinium enhancement, bilateral vestibular schwannomas
      were detected and a final diagnosis of NF2 was thus made. The association between
      NF2 and multiple depigmented spots is unknown, we therefore consider that
      multiple cutaneous plexiform schwannomas may strongly suggest an association with
      NF2.

PMID- 17204105
TI  - Bowen's disease concealed by purpura.
AB  - Bowen's disease (BD) is a squamous cell carcinoma in situ characterized by a well
      demarcated scaly erythematous thin plaque with an irregular outline. Clinically,
      BD is frequently misdiagnosed as superficial basal cell carcinoma, patches of
      dermatitis, psoriasis, lichen planus, actinic keratosis, benign lichenoid
      keratosis, irritated seborrheic keratosis, viral warts, amelanotic melanoma or
      melanoma. However, angiosarcoma has not usually been mentioned in the
      differential diagnosis of BD before. Herein, we describe two cases of BD
      presenting as purpura on the scalp of the elderly with an initial clinical
      suspicion of angiosarcoma.

PMID- 17204106
TI  - Zosteriform skin involvement of nodal T-cell lymphoma: a review of the published
      work of cutaneous malignancies mimicking herpes zoster.
AB  - A 77-year-old Japanese woman initially presented with non-Hodgkin's lymphoma
      involving her neck, axillary and inguen lymph nodes. She had edematous erythema
      and nodules limited to the skin in zosteriform distribution on the left side
      chest wall along the T4-5 dermatome. In addition, since 1970, we have mainly been
      collecting English-language articles on malignant skin tumors and skin metastasis
      described as zosteriform in the title, and we have reviewed a total of 29 cases,
      including our own. It should be mentioned that 59% of the cases reported had been
      diagnosed with herpes zoster at the time of the initial examination and that many
      of them had received drug therapy (e.g. acyclovir). We wish to add the dermatomic
      eruption mimicking zoster sine herpete to the list of possible presentations of
      cutaneous malignancies.

PMID- 17204107
TI  - Drug eruption caused by ranitidine hydrochloride (Zantac) which showed a strong
      reaction in a drug-induced lymphocyte stimulation test.
AB  - An 80-year-old male who developed a generalized papular erythema-type drug
      eruption after being treated with ranitidine hydrochloride is herein reported.
      The duration from the intake of the medicine to the onset of the eruption was 3
      days, and the eruption remained unchanged for a week after withdrawal of the
      medicine and even after the eruption itself was treated. A diagnosis of drug
      eruption by ranitidine hydrochloride was confirmed based on a strongly-positive
      reaction of a drug-induced lymphocyte stimulation test (DLST).

PMID- 17204108
TI  - Bullous eosinophilic cellulitis succession with eosinophilic pustular
      folliculitis without eosinophilia.
AB  - Eosinophilic cellulitis is characterized clinically by an acute dermatitis
      resembling cellulitis with unknown etiology. Eosinophilic pustular folliculitis
      is also a rare inflammatory dermatosis characterized by recurrent crops of
      erythematous follicular papulopustules that coalesce to form annular plaques with
      unclear etiopathogenesis. We describe a 20-year-old white male who had
      vesiculobullous and plaque-like lesions on the hands and feet and was diagnosed
      with bullous eosinophilic cellulitis clinically and histologically without any
      etiological agents. Following therapy with oral corticosteroid and oral
      tetracycline capsules, the lesions disappeared. After a 2-month asymptomatic
      period, the patient developed pruritic follicular papules and pustules on the
      lower and upper extremities and upper back. Stool examination revealed Gierdia
      intestinalis eggs. The patient had complete clearance with treatment of ornidazol
      for 2 weeks and indomethacin for 2 months. This is the first report of bullous
      eosinophilic cellulitis coexisting with eosinophilic pustular folliculitis
      without eosinophilia in the English published work.

PMID- 17204109
TI  - Tuberculous gumma associated with idiopathic thrombocytopenic purpura: report of
      a Japanese female patient.
AB  - Our patient was a 77-year-old Japanese woman, who was under treatment for
      idiopathic thrombocytopenic purpura (ITP) and chronic renal failure. She had warm
      nodules and cord-like induration on her left knee that appeared similar to
      Bazin's erythema induratum. A chest X-ray examination revealed miliary
      tuberculosis; after anti-mycobacterial therapy, the warm nodules and cord-like
      induration were transformed into a cold, non-tender abscess that drained.
      Histopathological findings showed caseation necrosis in the subcutaneous tissue,
      however, mycobacteria were directly detected by Ziehl-Neelsen staining from
      cutaneous lesions, and cultures from the same lesion also grew Mycobacterium
      tuberculosis. Tuberculous gumma demonstrated multiple, cold, painless abscesses
      and thrombosis were also seen. This is a rare and unusual clinical form of
      cutaneous tuberculosis, and the result of hematogenous dissemination from a
      primary focus during periods of lowered resistance.

PMID- 17204110
TI  - Case of fasciitis panniculitis syndrome.

PMID- 17204112
TI  - Sensitivity analysis of transient population dynamics.
AB  - Short-term, transient population dynamics can differ in important ways from long
      term asymptotic dynamics. Just as perturbation analysis (sensitivity and
      elasticity) of the asymptotic growth rate reveals the effects of the vital rates
      on long-term growth, the perturbation analysis of transient dynamics can reveal
      the determinants of short-term patterns. In this article, I present a completely
      new approach to transient sensitivity and elasticity analysis, using methods from
      matrix calculus. Unlike previous methods, this approach applies not only to
      linear time-invariant models but also to time-varying, subsidized, stochastic,
      nonlinear and spatial models. It is computationally simple, and does not require
      calculation of eigenvalues or eigenvectors. The method is presented along with
      applications to plant and animal populations.

PMID- 17204113
TI  - Scale dependence of the correlation between human population presence and
      vertebrate and plant species richness.
AB  - Human presence is generally negatively related to species richness locally, but
      the relationship is positive at coarse scales. An increase in the strength of the
      latter correlation with increasing study resolution has been documented within
      studies, but it is not known whether such a scale dependence is present across
      different studies. We test this with data on the spatial co-occurrence of human
      beings and the species richness of plants and vertebrates from a continuum of
      scales. The correlation coefficient between human presence and species richness
      is positively related to study grain and extent. The correlation turns from
      positive to negative below a study grain of c. 1 km and below a study extent of
      c. 10,000 km(2). The broad-scale positive correlation between human presence and
      species richness suggests that people have preferentially settled and generally
      flourished in areas of high biodiversity and/or have contributed to it with
      species introductions and habitat diversification. The scale dependency of the
      correlation between people and biodiversity's presence emphasizes the importance
      of the preservation of green areas in densely populated regions.

PMID- 17204114
TI  - Should conservation strategies consider spatial generality? Farmland birds show
      regional not national patterns of habitat association.
AB  - A key assumption underlying any management practice implemented to aid wildlife
      conservation is that it will have similar effects on target species across the
      range it is applied. However, this basic assumption is rarely tested. We show
      that predictors [nearly all associated with agri-environment scheme (AES) options
      known to affect European birds] had similar effects for 11 bird species on sites
      with differing farming practice (pastoral vs. mixed farming) or which differed in
      the density at which the species was found. However, predictors from sites in one
      geographical region tended to have different effects in other areas suggesting
      that AES options targeted at a regional scale are more likely to yield beneficial
      results for farmland birds than options applied uniformly in national schemes.
      Our study has broad implications for designing conservation strategies at an
      appropriate scale, which we discuss.

PMID- 17204115
TI  - Invasion speed is affected by geographical variation in the strength of Allee
      effects.
AB  - Allee effects can play a critical role in slowing or preventing the establishment
      of low density founder populations of non-indigenous species. Similarly, the
      spread of established invaders into new habitats can be influenced by the degree
      to which small founder populations ahead of the invasion front are suppressed
      through Allee effects. We develop an approach to use empirical data on the gypsy
      moth, a non-indigenous invader in North America, to quantify the Allee threshold
      across geographical regions, and we report that the strength of the Allee effect
      is subject to spatial and temporal variability. Moreover, we present what is to
      our knowledge the first empirical evidence that geographical regions with higher
      Allee thresholds are associated with slower speeds of invasion.

PMID- 17204116
TI  - Rapid evolution and ecological host-parasite dynamics.
AB  - Traditionally, the termination of parasite epidemics has been attributed to
      ecological causes: namely, the depletion of susceptible hosts as a result of
      mortality or acquired immunity. Here, we suggest that epidemics can also end
      because of rapid host evolution. Focusing on a particular host-parasite system,
      Daphnia dentifera and its parasite Metschnikowia bicuspidata, we show that
      Daphnia from lakes with recent epidemics were more resistant to infection and had
      less variance in susceptibility than Daphnia from lakes without recent epidemics.
      However, our studies revealed little evidence for genetic variation in
      infectivity or virulence in Metschnikowia. Incorporating the observed genetic
      variation in host susceptibility into an epidemiological model parameterized for
      this system reveals that rapid evolution can explain the termination of epidemics
      on time scales matching what occurs in lake populations. Thus, not only does our
      study provide rare evidence for parasite-mediated selection in natural
      populations, it also suggests that rapid evolution has important effects on short
      term host-parasite dynamics.

PMID- 17204117
TI  - Does complementary resource use enhance ecosystem functioning? A model of light
      competition in plant communities.
AB  - Recent experiments on grassland ecosystems have shown that biodiversity can
      enhance ecosystem processes such as plant biomass production. Functional
      complementarity is generally regarded as the main class of mechanisms generating
      these effects of biodiversity on ecosystem functioning. Although intuitively
      appealing and supported by some data, the complementarity hypothesis has been
      little explored theoretically using mechanistic approaches. Here, we present a
      simple dynamical model for a light-limited terrestrial ecosystem to assess the
      effects of species diversity on light competition and total biomass in plant
      communities. Our model shows that competitive relaxation (reduction in average
      light competition intensity) due to differences in foliar architecture among
      species enhances total plant biomass in mixtures, but that competitive imbalance
      (generated by the variance of the average light competition intensity experienced
      by different species) can either reinforce the effect of competitive relaxation
      or counteract it and contribute to reducing total plant biomass. Thus,
      complementary resource use is not enough to increase total plant biomass in
      species-rich communities; competitive balance among species also plays an
      important role. We propose an operational measure of light-use complementarity
      using empirical field data on light absorption to test the presence of
      complementarity in natural plant communities.

PMID- 17204118
TI  - Towards genetic markers in animal populations as biomonitors for human-induced
      environmental change.
AB  - Genetic markers provide potentially sensitive indicators of changes in
      environmental conditions because the genetic constitution of populations is
      normally altered well before populations become extinct. Genetic indicators in
      populations include overall genetic diversity, genetic changes in traits measured
      at the phenotypic level, and evolution at specific loci under selection. While
      overall genetic diversity has rarely been successfully related to environmental
      conditions, genetically based changes in traits have now been linked to the
      presence of toxins and both local and global temperature shifts. Candidate loci
      for monitoring stressors are emerging from information on how specific genes
      influence traits, and from screens of random loci across environmental gradients.
      Drosophila research suggests that chromosomal regions under recent intense
      selection can be identified from patterns of molecular variation and a high
      frequency of transposable element insertions. Allele frequency changes at
      candidate loci have been linked to pesticides, pollutants and climate change.
      Nevertheless, there are challenges in interpreting allele frequencies in
      populations, particularly when a large number of loci control a trait and when
      interactions between alleles influence trait expression. To meet these
      challenges, population samples should be collected for longitudinal studies, and
      experimental programmes should be undertaken to link variation at candidate genes
      to ecological processes.

PMID- 17204119
TI  - Invasion in a heterogeneous world: resistance, coexistence or hostile takeover?
AB  - We review and synthesize recent developments in the study of the invasion of
      communities in heterogeneous environments, considering both the invasibility of
      the community and impacts to the community. We consider both empirical and
      theoretical studies. For each of three major kinds of environmental heterogeneity
      (temporal, spatial and invader-driven), we find evidence that heterogeneity is
      critical to the invasibility of the community, the rate of spread, and the
      impacts on the community following invasion. We propose an environmental
      heterogeneity hypothesis of invasions, whereby heterogeneity both increases
      invasion success and reduces the impact to native species in the community,
      because it promotes invasion and coexistence mechanisms that are not possible in
      homogeneous environments. This hypothesis could help to explain recent findings
      that diversity is often increased as a result of biological invasions. It could
      also explain the scale dependence of the diversity-invasibility relationship.
      Despite the undoubted importance of heterogeneity to the invasion of communities,
      it has been studied remarkably little and new research is needed that
      simultaneously considers invasion, environmental heterogeneity and community
      characteristics. As a young field, there is an unrivalled opportunity for
      theoreticians and experimenters to work together to build a tractable theory
      informed by data.

PMID- 17204121
TI  - Postnatal development of canine axial globe length measured by B-scan
      ultrasonography.
AB  - OBJECTIVE: The objectives of this study were to document the development of axial
      globe length (AGL) in normal mesocephalic cross-bred dogs between 2 and 52 weeks
      of age, to determine a relationship between AGL and age, and derive an equation
      to predict AGL in normal mesocephalic cross-bred dogs. ANIMALS STUDIED AND
      PROCEDURE: The AGL of twenty normal mesocephalic cross-bred dogs was measured at
      12 time points from 2 to 52 weeks of age using B-scan ultrasonography. RESULTS:
      The mean (+/- SEM) AGL increased from 12.65 mm (+/- 0.18) at 2 weeks of age to
      19.52 mm (+/- 0.18) at 52 weeks of age. The correlation between AGL and age was
      evaluated by fitting possible variables to a regression pattern. A linear model
      of natural logarithmic-transformed value of AGL (mm) and age (week) was
      established. Side (left or right eye) and gender did not correlate with
      development of AGL. CONCLUSIONS: A reverse transformation of the formula can be
      used to predict AGL in mesocephalic cross-bred dogs: AGL = 10.847 * age in weeks
      0.1653.

PMID- 17204122
TI  - Entropion correction in dogs and cats using a combination Hotz-Celsus and lateral
      eyelid wedge resection: results in 311 eyes.
AB  - A novel surgical combination technique for the correction of lateral lower lid
      entropion in dogs and cats is described, involving a combination of Hotz-Celsus
      and lateral eyelid wedge resection procedures. The technique was used to treat
      311 eyes with lower lid entropion: 269 canine (109 bilateral, 51 unilateral) and
      42 feline (16 bilateral, 10 unilateral). The most common canine breeds were the
      Shar Pei, Rottweiler, Bull Mastiff and Labrador Retriever. Domestic cats made up
      the majority of feline cases. The overall success rate for a single surgical
      procedure to correct lower lid entropion with this technique was 94.2% per eye.

PMID- 17204123
TI  - Comparison of cytologic and histologic evaluations of the conjunctiva in the
      normal equine eye.
AB  - OBJECTIVE: To describe the cells observed in conjunctival brush cytology (CBC)
      from normal horses and compare these findings with conjunctival structural
      histology so as to understand which cells are recovered from CBC. METHODS: This
      study was divided into three parts. (1) Conjunctival brush smears were collected
      from 20 healthy horses on both eyes and a differential count on 300 cells was
      carried out on May Grunwald-Giemsa (MGG) smears. (2) A similar protocol was used
      for whole eyes from five horses obtained rapidly after death from a
      slaughterhouse. The eyes were then assessed for conjunctival histology. (3)
      Cytobrush smears were collected from five healthy horses. Smears were examined
      after MGG or periodic acid Schiff (PAS) staining. RESULTS: The differential cell
      count showed a majority of deep and intermediate epithelial cells with very few
      superficial and goblet cells in both eyes. A stratified columnar to cuboidal
      epithelium was observed on nearly the whole surface of the conjunctiva. A
      stratified squamous type was observed at the palpebral and bulbar edges. Areas
      with highest mucus cell indices were found from the nasal to the temporal edge of
      the equine inferior conjunctiva in the upper palpebral segment near the fornix
      and in a part of the nasal fornix. In MGG smears no mucus cells were identified;
      however, they were numerous in PAS smears (22.6% +/- 11) and were mostly
      cylindrical cells (42.5% +/- 14.4 PAS positive). CONCLUSIONS: Cytobrush smears in
      the healthy horse are characterized by a majority of polyhedral and cylindrical
      cells and a few squamous cells. The cylindrical cells may be mucous cells and
      probably originate from the main stratified columnar to cuboidal epithelium.

PMID- 17204124
TI  - A retrospective evaluation of congenital ocular defects in Australian Shepherd
      dogs in Australia.
AB  - OBJECTIVE: A retrospective survey of ocular defects in Australian Shepherd dogs
      was conducted following concerns raised by breeders and owners in Australia. This
      is the first known such study conducted for this breed. RESULTS: Data from this
      survey indicate that persistent hyaloid remnants (PHR) were the most common eye
      defect noted in the Australian Shepherd. Collie eye anomaly (CEA) is the second
      most common defect noted by veterinary ophthalmologists in the breed in
      Australia, and extra eyelashes (ectopic cilia/distichia) the third most common.
      CONCLUSIONS: The data also support the hypothesis that PHR may be inherited in
      this breed. Further investigation is needed to reveal the status of PHR in this
      breed.

PMID- 17204125
TI  - Presumed and confirmed striatocapsular brain infarctions in six dogs.
AB  - OBJECTIVE: To describe the clinical and diagnostic features of the canine
      sensorimotor syndrome caused by striatocapsular brain infarctions (SCI). ANIMALS
      STUDIED: Six dogs with diagnostic imaging or postmortem evidence of SCI.
      PROCEDURES: Medical records of dogs with SCI were retrospectively reviewed and
      the signalment, history, clinical signs, antemortem clinicopathologic test
      results, diagnostic imaging findings, case outcomes, and pathologic findings
      recorded. RESULTS: All dogs had an acute onset of nonprogressive homonymous
      visual field deficits and contralateral general proprioceptive (GP) deficits.
      Contralateral hemiparesis and facial hypalgesia were noted in 5/6 dogs. CT scans
      were normal in 2/4 dogs, and revealed poorly defined hypoattenuating lesions in
      the subcortical white matter in two dogs. MRI exams were performed in 5/6 dogs
      and revealed unilateral, variably sized, striatocapsular lesions consistent with
      nonhemorrhagic infarctions. Diagnostic imaging (6/6) and postmortem examinations
      (2/6) suggested that SCI resulted from lesions in the vascular territories of the
      rostral choriodal (6/6) and lenticulostriate arteries (2/6). Diseases
      predisposing to infarction were not identified in 5/6 dogs. Improvements in
      mentation, behavior, proprioceptive deficits, and hemiparesis were seen in
      surviving dogs, but persistent, symptomatic sensory deficits were noted during
      the follow-up period. CONCLUSIONS: SCI should be considered as a differential
      diagnosis for dogs with acute onset, nonprogressive homonymous hemianopia,
      contralateral GP deficits or hemiparesis, and facial hypalgesia. MRI is the
      preferred modality for the antemortem imaging diagnosis of SCI. Although partial
      recovery occurred in all surviving dogs, visual and facial sensory disturbances
      persisted.

PMID- 17204126
TI  - Combined keratectomy, strontium-90 irradiation and permanent bulbar conjunctival
      grafts for corneolimbal squamous cell carcinomas in horses (1990-2002): 38
      horses.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effectiveness of
      postoperative beta-irradiation with strontium-90 as an adjunctive treatment to
      superficial keratectomy and permanent bulbar conjunctival graft for removal of
      equine corneolimbal squamous cell carcinoma (SCC), in decreasing recurrence rate.
      STUDY: The retrospective case study included 38 horses diagnosed and treated for
      SCC of the eye that involved the limbus and/or cornea. The patients were treated
      between 1990 and 2002, with strontium-90 irradiation immediately after corneal
      and conjunctival graft surgery. Recurrence was defined as the postoperative and
      postirradiation regrowth of SCC in the same site and globe that was previously
      treated. RESULTS: The Appaloosa was the most commonly represented breed and
      horses that had more than one base coat color represented the majority of the
      cases (53%). The coat colors of white, chestnut/sorrel and gray were the most
      commonly represented colors of the horses treated. Eight horses (21%) could not
      be assessed for tumor recurrence due to lack of two or more post-treatment
      examinations, and another horse was enucleated 6 days postoperatively due to
      progressive corneal ulceration. Twenty-four horses (63% of the entire study
      population; 83% of the followed cases) had a mean +/- SD of 1754 +/- 1319 days
      without tumor recurrence, ranging from 14 days to 5110 days. Five horses (13% of
      the entire study population; 17% of the assessed horses) had tumor recurrence at
      a mean +/- SD of 449 +/- 339 days with a range of 29 days to 900 days. For the
      five recurrences, treatment included local excision (n = 1), enucleation (n = 2),
      and additional strontium-90 therapy (n = 3). CONCLUSIONS: The combination of
      superficial keratectomy, beta-irradiation and permanent bulbar conjunctival
      grafts for limbal, corneal or corneolimbal SCC in horses is effective in at least
      83% of the horses. Recurrence occurred in about 17% of the horses. Multiple
      biannual re-examinations are recommended to observe for tumor recurrence.

PMID- 17204127
TI  - Ocular findings in two colonies of gray mouse lemurs (Microcebus murinus).
AB  - OBJECTIVE: To determine the incidence and describe the characteristics of
      cataracts and other ocular lesions found in two colonies of gray mouse lemurs
      (Microcebus murinus). ANIMALS STUDIED: A total number of 218 mouse lemurs (age
      range: 4 months-11 years) were included in this study. All individuals were
      property of the Museum National d'Histoire Naturelle (France), and were housed
      either in Paris (colony #1: 75 animals examined), or in Brunoy (colony #2: 143
      animals). METHODS: Ocular examinations were performed on all animals before and
      after pupil dilation, and included slit-lamp biomicroscopy and indirect
      ophthalmoscopy. In both colonies, a limited number of individuals were re
      examined between several months and 2 years following the initial eye
      examinations. The eyes of five mouse lemurs with incipient or immature cataracts
      that died during this period were collected, and processed for routine
      histopathologic examination. RESULTS: A high incidence of cataracts was observed
      in both colonies (48% in colony #1; 21% in colony #2). Cataracts were
      predominantly bilateral, started in the anterior and/or posterior subcapsular
      area, and appeared to be slowly progressive. The earliest age at which lens
      opacities were observed was 3.5 years, and more than 50% of mouse lemurs over 7
      years of age were diagnosed with cataracts. Complete cataracts led to blindness
      and were occasionally associated with other ocular lesions. CONCLUSION: We report
      a high incidence of acquired, slowly progressive, bilateral cataracts in two
      colonies of mouse lemurs (Microcebus murinus). Further studies need to be
      conducted to determine the cause of this disease in this species.

PMID- 17204128
TI  - Ocular biometry in the adult anesthetized ferret (Mustela putorius furo).
AB  - A total of 44 eyes of 22 ferrets were examined by B-mode ultrasonography. Four
      dimensions were measured: the distance from the corneal surface to the anterior
      lens surface (M1), the axial lens thickness (M2), the distance from the posterior
      lens surface to the retina (M3) and the distance from the anterior cornea to the
      retina (M4). The values obtained were (mean, standard deviation, range): M1: 1.31
      +/- 0.16 mm (1-1.7); M2: 3.42 +/- 0.15 mm (3.2-3.7); M3: 2.26 +/- 0.11 mm (2.1
      2.5); M4: 7 +/- 0.24 mm (6.4-7.7). To our knowledge this is the first description
      of ocular biometric measurement in the ferret. These values show little
      variability of ocular dimensions in ferrets.

PMID- 17204129
TI  - Taenia coenurus in the orbit of a chinchilla.
AB  - A 4-year old, male intact, captive-bred chinchilla (Chinchilla lanigera) was
      presented due to progressive exophthalmos of the right eye over a 5-month period.
      Ophthalmic examination revealed exophthalmos with dorsal displacement of the
      right globe. Retropulsion was decreased and a fluctuant, subcutaneous mass could
      be palpated posterior and dorsal to the central aspect of the zygomatic bone.
      Transdermal ultrasonography revealed a fluid-filled mass consistent with a cyst
      located within the ventral right orbit. Computed tomography demonstrated dorsal
      displacement of the globe, lateral displacement of the zygomatic arch, and
      numerous mineral-dense foci within the lumen of the cyst. The cyst was removed en
      bloc by ventral transpalpebral orbitotomy. Histopathology revealed a single
      capsulated cyst with multiple invaginated protoscolices, characterized by a
      prominent scolex with refractile hooklets, suckers, and abundant calcareous
      corpuscles consistent with a Taenia coenurus. Exophthalmos resolved with surgical
      therapy and there was no evidence of recurrence or postoperative complications
      over a period of 2 years. To the authors' knowledge, this is the first reported
      case of an orbital cyst of parasitic origin in a chinchilla.

PMID- 17204130
TI  - Primary conjunctival mast cell tumor in a Labrador Retriever.
AB  - A 4-year-old, intact male Labrador Retriever with a rapidly progressive
      conjunctival mass was evaluated. Ocular examination showed a 2-cm elongated mass
      arising from the superior bulbar conjunctiva of the left eye. The mass resulted
      in distortion of the palpebral fissure and contacted the superior aspect of the
      cornea without modifying its structure; no adhesion to the sclera was detected.
      The superior palpebral conjunctiva was unaffected, and the remaining ocular
      examination was normal. The initial diagnostic work-up included CBC, serum
      biochemical analysis, urinalysis, and fine needle biopsy of the mass. A poorly
      differentiated mast cell tumor was diagnosed by cytology. Immunocytochemistry was
      performed to evaluate Ki-67 proliferation index, and 54/1000 tumoral nuclei
      showed a dark red staining. After a complete clinical staging, the mass was
      excised and identified histologically as a grade-II mast cell tumor. An adjuvant
      treatment with prednisone and vinblastine was instituted because of the limited
      excisional margins. No evidence of local recurrence or metastasis has been
      apparent during the 29-month follow-up period. This report contributes to the
      current literature pertaining to canine conjunctival mast cell tumors;
      unfortunately, the paucity of case reports and the absence of large studies
      regarding this tumor make conclusions regarding its biologic behavior impossible.

PMID- 17204131
TI  - Use of a dermal biopsy punch for removal of ectopic cilia in dogs: 19 cases.
AB  - OBJECTIVE: To evaluate the use of a dermal biopsy punch for accurate and quick
      removal of ectopic cilia in dogs. ANIMALS STUDIED: This study reports the
      treatment of ectopic cilia detected in 12 dogs during the period from June 2002
      to December 2004. Five cases were affected with ectopic cilia in the right eye,
      and five in the left eye, with two cases affected bilaterally. Nineteen ectopic
      cilia were detected in 12 dogs. PROCEDURE: The technique described in this study
      consists of using a 2-3-mm skin biopsy punch with the aid of an operating
      microscope. RESULTS: No recurrence was noted in any of the cases. The presurgical
      blepharospasm due to the presence of the cilia resolved as well as uneventful
      corneal healing of any associated corneal erosions or ulcers. CONCLUSIONS: This
      method offers a simple, practical alternative to the traditional scalpel
      procedure as described in the veterinary ophthalmic literature.

PMID- 17204132
TI  - Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for
      cardiovascular death in patients with coronary artery disease: the AtheroGene
      study.
AB  - BACKGROUND: Tissue factor (TF) and its specific inhibitor, tissue factor pathway
      inhibitor (TFPI), are important contributors to the initiation of the coagulation
      process. OBJECTIVES: To compare plasma levels of soluble TF (sTF) and free-TFPI
      (f-TFPI) between patients with stable angina pectoris (SAP) and acute coronary
      syndrome (ACS) and to assess the impact of the two variables on long-term
      prognosis. PATIENTS/METHODS: Patients with SAPs (n = 1146) and acute coronary
      syndrome (n = 523) from the AtheroGene study were included and followed for 2.3
      years. Because of the strong impact of unfractionated heparin (UFH) on f-TFPI
      levels, but not on sTF levels, patients having received UFH before blood drawing
      were excluded from the analyses on f-TFPI (n = 226). RESULTS: On admission, no
      significant differences in sTF levels were observed between SAP and ACS patients.
      By comparison to patients with stable angina, f-TFPI levels significantly
      increased in patients with acute unstable angina and further increased in
      patients presenting with non-ST-elevation myocardial infarction and ST-elevation
      myocardial infarction (P < 10(-4)). Among the 1669 individuals with a coronary
      artery disease, 56 died from a cardiovascular cause. In prospective analyses,
      high sTF levels were independently associated with an increased risk of
      cardiovascular death in individuals with ACS (fully adjusted hazard ratio
      associated with one quartile increase = 2.06; 95% confidence interval 1.24-3.45;
      P = 0.006) but not in those with SAP (hazard ratio = 1.07; 95% confidence
      interval 0.78-1.46; P = 0.67). In SAP and ACS patients, high f-TFPI levels were
      not independently associated with an increased risk of cardiovascular death.
      CONCLUSIONS: Plasma sTF levels were predictive of cardiovascular mortality in
      individuals with ACS, whereas f-TFPI levels were associated with the severity of
      myocardial damage on admission but were not independently related to outcome.

PMID- 17204134
TI  - Sinus lifting before Le Fort I maxillary osteotomy: a suitable method for oral
      rehabilitation of edentulous patients with skeletal class-III conditions: review
      of the literature and report of a case.
AB  - BACKGROUND: Functional rehabilitation of patients afflicted with severe
      mandibular and maxillary alveolar atrophy might be challenging especially in
      malformed patients. METHODS: Treatment planning using sinus lifting and implant
      placement before Le Fort I maxillary osteotomy in a patient with severe
      mandibular and posterior maxillary alveolar atrophy and skeletal class-III
      conditions due to cleft palate are described. RESULTS: A full functional and
      esthetic rehabilitation of the patient was achieved by a stepwise surgical
      approach performed through sinus lifting as the primary approach followed by
      implant placement and subsequent Le Fort I maxillary osteotomy to correct the
      maxillo-mandibular relation. CONCLUSION: Stabilisation of the maxillary complex
      by a sinus lifting procedure in combination with computer aided implant placement
      as preorthodontic planning procedure before Le Fort I maxillary osteotomy seems
      to be suitable in order to allow ideal oral rehabilitation especially in
      malformed patients.

PMID- 17204135
TI  - Neuromuscular deterioration in the early stage of sepsis in rats.
AB  - INTRODUCTION: Critical illness polyneuropathy (CIP) is a clinical condition
      frequently seen in patients being treated in critical care units in the final
      stage of sepsis. The etiopathology of CIP is still unclear, and the onset time of
      appearance of the electrophysiological findings has not been elucidated. The very
      little research that has been carried out on this topic is limited to clinical
      electrophysiological and histopathological studies. In this study,
      electrophysiological alterations in the early stage of experimentally induced
      sepsis were investigated in septic rats. METHODS: We conducted a prospective,
      randomized, controlled experimental study in an animal basic science laboratory
      with 30 male Sprague-Dawley rats, weighing 200 to 250 g. All of the rats were
      randomly assigned to one of two groups. In the sepsis group (n = 20), cecal
      ligation and puncture (CLP) was performed to induce experimental sepsis. In the
      sham-operated group (n = 10), laparotomy without CLP was performed. Before and 24
      hours after CLP and laparotomy, the right sciatic nerve was stimulated from the
      sciatic notch and compound muscle action potentials (CMAPs) were recorded from
      the gastrocnemius muscle. Recordings of latency, amplitude, and duration of the
      CMAP were evaluated. RESULTS: CMAP durations before and 24 hours after surgery
      were 0.45 +/- 0.05 ms and 0.48 +/- 0.05 ms, respectively, in the sham-operated
      group and 0.46 +/- 0.05 ms and 0.55 +/- 0.01 ms, respectively, in the sepsis
      group. Latency measurements in the sham-operated group were 0.078 +/- 0.010 ms
      and 0.080 +/- 0.015 ms, respectively, whereas measurements were found to be
      prolonged in the sepsis group: 0.094 +/- 0.015 ms and 0.149 +/- 0.054 ms before
      and 24 hours after surgery, respectively (p < 0.05). CMAP amplitudes in the sham
      operated group before and 24 hours after surgery were 8.41 +/- 0.79 mV and 8.28
      +/- 1.92 mV, respectively, whereas in the sepsis group the amplitude measurements
      decreased to 7.60 +/- 1.75 mV and 4.87 +/- 3.44 mV, respectively (p < 0.05).
      CONCLUSION: The results of the study indicate that electrophysiological
      alterations appear in the first 24 hours after experimental sepsis and are
      characterized by an increase in latency and a decrease in CMAP amplitude. The
      results also suggest that electrophysiological findings seen in patients with CIP
      might appear before clinical signs of CIP.

PMID- 17204136
TI  - Protocol for the THREAD (THREshold for AntiDepressants) study: a randomised
      controlled trial to determine the clinical and cost-effectiveness of
      antidepressants plus supportive care, versus supportive care alone, for mild to
      moderate depression in UK general practice.
AB  - BACKGROUND: Depression guidelines in the UK recommended a policy of watchful
      waiting for mild depression due to a lack of evidence for the effectiveness of
      antidepressant treatment for mild cases. However there has been relatively little
      research carried out in primary care to help establish the severity threshold at
      which antidepressant treatment is effective and cost-effective. METHODS/DESIGN:
      The THREAD (THREshold for AntiDepressants) study is a multi-centre randomised
      controlled trial designed to determine the clinical and cost effectiveness of a
      selective serotonin reuptake inhibitor (SSRI) plus general practitioner (GP)
      supportive care, versus supportive care alone, for mild to moderate depression in
      primary care. The aim is to recruit 300 patients from three centres (Southampton,
      London and Liverpool). Depressive symptoms will be assessed at baseline, 12 weeks
      and 26 weeks, using the 17-item Hamilton Depression Rating Scale (HDRS). Two
      severity sub-groups of patients will be recruited, with HDRS scores of 12-15, and
      16-19. Possible predictors of response will be explored including life events and
      difficulties and alcohol consumption. Analysis of covariance, controlling for
      baseline value, severity group and centre will be used to estimate the overall
      treatment effectiveness (difference in HDRS score) at final follow up. The
      primary analysis will be by 'intention to treat' using double sided tests. The
      interaction between severity sub-group and treatment will be tested, and if
      appropriate, effects within separate severity sub-groups estimated. The economic
      analysis will compare the two treatment groups in terms of mean costs and cost
      effectiveness. DISCUSSION: The results of this study will give GPs important
      information to help them determine the severity of depression at which
      antidepressant treatment is likely to be cost-effective.

PMID- 17204137
TI  - Double-chambered right ventricle in an adult patient diagnosed by transthoracic
      echocardiography.
AB  - BACKGROUND: Double-chambered right ventricle is a rare congenital disease
      frequently misdiagnosed in the adult patient. An anomalous muscle band divides
      the right ventricle in two cavities causing variable degree of obstruction.
      Although echocardiography is considered a useful method for the diagnosis of this
      pathology in children, it has been recognized the transthoracic scanning
      limitation in adults. CASE PRESENTATION: A 29 year-old patient with double
      chambered right ventricle presenting mild exercise intolerance referred for
      follow up of a known ventricular septal defect in whom a complete diagnosis was
      obtained based only on transthoracic two dimensional echocardiography without the
      needing of cardiac catheterization. CONCLUSION: Based on non invasive
      echocardiographic diagnosis, patient was referred to surgical correction, which
      was completely successful.

PMID- 17204138
TI  - Single trial somatosensory evoked potential extraction with ARX filtering for a
      combined spinal cord intraoperative neuromonitoring technique.
AB  - BACKGROUND: When spinal cord functional integrity is at risk during surgery,
      intraoperative neuromonitoring is recommended. Tibial Single Trial Somatosensory
      Evoked Potentials (SEPs) and H-reflex are here used in a combined neuromonitoring
      method: both signals monitor the spinal cord status, though involving different
      nervous pathways. However, SEPs express a trial-to-trial variability that is
      difficult to track because of the intrinsic low signal-to-noise ratio. For this
      reason single trial techniques are needed to extract SEPs from the background
      EEG. METHODS: The analysis is performed off line on data recorded in eight
      scoliosis surgery sessions during which the spinal cord was simultaneously
      monitored through classical SEPs and H-reflex responses elicited by the same
      tibial nerve electrical stimulation. The single trial extraction of SEPs from the
      background EEG is here performed through AutoRegressive filter with eXogenous
      input (ARX). The electroencephalographic recording can be modeled as the sum of
      the background EEG, which can be described as an autoregressive process not
      related to the stimulus, and the evoked potential (EP), which can be viewed as a
      filtered version of a reference signal related to the stimulus. The choice of the
      filter optimal orders is based on the Akaike Information Criterion (AIC). The
      reference signal used as exogenous input in the ARX model is a weighted average
      of the previous SEPs trials with exponential forgetting behavior. RESULTS: The
      moving average exponentially weighted, used as reference signal for the ARX
      model, shows a better sensibility than the standard moving average in tracking
      SEPs fast inter-trial changes. The ability to promptly detect changes allows
      highlighting relations between waveform changes and surgical maneuvers. It also
      allows a comparative study with H-reflex trends: in particular, the two signals
      show different fall and recovery dynamics following stressful conditions for the
      spinal cord. CONCLUSION: The ARX filter showed good performances in single trial
      SEP extraction, enhancing the available information concerning the current spinal
      cord status. Moreover, the comparison between SEPs and H-reflex showed that the
      two signals are affected by the same surgical maneuvers, even if they monitor the
      spinal cord through anatomically different pathways.

PMID- 17204139
TI  - The alternative sigma factor SigB of Corynebacterium glutamicum modulates global
      gene expression during transition from exponential growth to stationary phase.
AB  - BACKGROUND: Corynebacterium glutamicum is a gram-positive soil bacterium widely
      used for the industrial production of amino acids. There is great interest in the
      examination of the molecular mechanism of transcription control. One of these
      control mechanisms are sigma factors. C. glutamicum ATCC 13032 has seven putative
      sigma factor-encoding genes, including sigA and sigB. The sigA gene encodes the
      essential primary sigma factor of C. glutamicum and is responsible for promoter
      recognition of house-keeping genes. The sigB gene codes for the non-essential
      sigma factor SigB that has a proposed role in stress reponse. RESULTS: The sigB
      gene expression was highest at transition between exponential growth and
      stationary phase, when the amount of sigA mRNA was already decreasing. Genome
      wide transcription profiles of the wild-type and the sigB mutant were recorded by
      comparative DNA microarray hybridizations. The data indicated that the mRNA
      levels of 111 genes are significantly changed in the sigB-proficient strain
      during the transition phase, whereas the expression profile of the sigB-deficient
      strain showed only minor changes (26 genes). The genes that are higher expressed
      during transition phase only in the sigB-proficient strain mainly belong to the
      functional categories amino acid metabolism, carbon metabolism, stress defense,
      membrane processes, and phosphorus metabolism. The transcription start points of
      six of these genes were determined and the deduced promoter sequences turned out
      to be indistinguishable from that of the consensus promoter recognized by SigA.
      Real-time reverse transcription PCR assays revealed that the expression profiles
      of these genes during growth were similar to that of the sigB gene itself. In the
      sigB mutant, however, the transcription profiles resembled that of the sigA gene
      encoding the house-keeping sigma factor. CONCLUSION: During transition phase, the
      sigB gene showed an enhanced expression, while simultaneously the sigA mRNA
      decreased in abundance. This might cause a replacement of SigA by SigB at the RNA
      polymerase core enzyme and in turn results in increased expression of genes
      relevant for the transition and the stationary phase, either to cope with
      nutrient limitation or with the accompanying oxidative stress. The increased
      expression of genes encoding anti-oxidative or protection functions also prepares
      the cell for upcoming limitations and environmental stresses.

PMID- 17204140
TI  - Normalization of boutique two-color microarrays with a high proportion of
      differentially expressed probes.
AB  - Normalization is critical for removing systematic variation from microarray data.
      For two-color microarray platforms, intensity-dependent lowess normalization is
      commonly used to correct relative gene expression values for biases. Here we
      outline a normalization method for use when the assumptions of lowess
      normalization fail. Specifically, this can occur when specialized boutique arrays
      are constructed that contain a subset of genes selected to test particular
      biological functions.

PMID- 17204141
TI  - Endoscopic management of hypertensive intraventricular haemorrhage with
      obstructive hydrocephalus.
AB  - BACKGROUND: Intracranial haemorrhage accounts for 30-60 % of all stroke
      admissions into a hospital, with hypertension being the main risk factor.
      Presence of intraventricular haematoma is considered a poor prognostic factor due
      to the resultant obstruction to CSF and the mass effect following the presence of
      blood resulting in raised intracranial pressure and hydrocephalus. We report the
      results following endoscopic decompression of obstructive hydrocephalus and
      evacuation of haematoma in patients with hypertensive intraventricular
      haemorrhage. METHODS: During a two year period, 25 patients diagnosed as having
      an intraventricular haemorrhage with obstructive hydrocephalus secondary to
      hypertension were included in this study. All patients underwent endoscopic
      evacuation of the haematoma under general anaesthesia. Post operative evaluation
      was done by CT scan and Glasgow outcome scale. RESULTS: Of the 25 patients,
      thalamic haemorrhage was observed in 12 (48%) patients, while, 11 (44%) had a
      putaminal haematoma. Nine (36%) patients had a GCS of 8 or less pre-operatively.
      Resolution of hydrocephalus following endoscopic evacuation was observed in 24
      (96%) patients. No complications directly related to the surgical technique were
      encountered in our study. At six months follow-up, a mortality rate of 6.3% and
      55.5% was observed in patients with a pre-operative GCS of > or = 9 and < or = 8
      respectively. Thirteen of the 16 (81.3%) patients with a pre-operative GCS >/= 9
      had good recovery. CONCLUSION: Endoscopic technique offers encouraging results in
      relieving hydrocephalus in hypertensive intraventricular haemorrhage. Final
      outcome is better in patient with a pre-operative GCS of >9. Future improvements
      in instrumentation and surgical techniques, with careful case selection may help
      improve outcome in these patients.

PMID- 17204142
TI  - All-trans retinoic acid induces COX-2 and prostaglandin E2 synthesis in SH-SY5Y
      human neuroblastoma cells: involvement of retinoic acid receptors and
      extracellular-regulated kinase 1/2.
AB  - BACKGROUND: Our recent results show that all-trans retinoic acid (ATRA), an
      active metabolite of vitamin A, induces COX-dependent hyperalgesia and allodynia
      in rats. This effect was mediated by retinoic acid receptors (RARs) and was
      associated with increased COX-2 expression in the spinal cord. Since ATRA also up
      regulated COX-2 expression in SH-SY5Y human neuroblastoma cells, the current
      study was undertaken to analyze in these cells the mechanism through which ATRA
      increases COX activity. METHODS: Cultured SH-SY5Y neuroblastoma cells were
      treated with ATRA. COX expression and kinase activity were analyzed by western
      blot. Transcriptional mechanisms were analyzed by RT-PCR and promoter assays.
      Pharmacological inhibitors of kinase activity and pan-antagonists of RAR or RXR
      were used to assess the relevance of these signaling pathways. Production of
      prostaglandin E2 (PGE2) was quantified by enzyme immunoabsorbent assay.
      Statistical significance between individual groups was tested using the non
      parametric unpaired Mann-Whitney U test. RESULTS: ATRA induced a significant
      increase of COX-2 expression in a dose- and time-dependent manner in SH-SY5Y
      human neuroblastoma cells, while COX-1 expression remained unchanged.
      Morphological features of differentiation were not observed in ATRA-treated
      cells. Up-regulation of COX-2 protein expression was followed by increased
      production of PGE2. ATRA also up-regulated COX-2 mRNA expression and increased
      the activity of a human COX-2 promoter construct. We next explored the
      participation of RARs and mitogen-activated peptide kinases (MAPK). Pre
      incubation of SH-SY5Y human neuroblastoma cells with either RAR-pan-antagonist
      LE540 or MAP kinase kinase 1 (MEK-1) inhibitor PD98059 resulted in the abolition
      of ATRA-induced COX-2 promoter activity, COX-2 protein expression and PGE2
      production whereas the retinoid X receptor pan-antagonist HX531, the p38 MAPK
      inhibitor SB203580 or the c-Jun kinase inhibitor SP600125 did not have any
      effect. The increase in RAR-beta expression and extracellular-regulated kinase
      1/2(ERK1/2) phosphorylation in ATRA-incubated cells suggested that RARs and
      ERK1/2 were in fact activated by ATRA in SH-SY5Y human neuroblastoma cells.
      CONCLUSION: These results highlight the importance of RAR-dependent and kinase
      dependent mechanisms for ATRA-induced COX-2 expression and activity.

PMID- 17204143
TI  - Health researchers in Alberta: an exploratory comparison of defining
      characteristics and knowledge translation activities.
AB  - BACKGROUND: Canadian funding agencies are no longer content to support research
      that solely advances scientific knowledge, and key directives are now in place to
      promote research transfer to policy- and decision-makers. Therefore, it is
      necessary to improve our understanding of how researchers are trained and
      supported to facilitate knowledge translation activities. In this study, we
      investigated differences in health researcher characteristics and knowledge
      translation activities. METHODS: Our sample consisted of 240 health researchers
      from three Alberta universities. Respondents were classified by research domain
      [basic (n = 72) or applied (n = 168)] and faculty [medical school (n = 128) or
      other health science (n = 112)]. We examined our findings using Mode I and Mode
      II archetypes of knowledge production, which allowed us to consider the scholarly
      and social contexts of knowledge production and translation. RESULTS: Differences
      among health researcher professional characteristics were not statistically
      significant. There was a significant gender difference in the applied researcher
      faculty group, which was predominantly female (p < .05). Research domain was
      linked to translation activities. Applied researchers reported engaging in
      significantly more Mode II activities than basic researchers (p < .001), and
      scored higher than basic researchers regarding the perceived importance of
      translation activities (Mode I, p = .01; Mode II, p < .001). Main effects of
      faculty were limited to engaged dissemination (medical school < other faculties;
      p = .025) and number of publications (medical school > other faculties; p =
      .004). There was an interaction effect for research domain and faculty group for
      number of publications (p = .01), in that applied researchers in medical
      faculties published more than their peers in other faculty groups. CONCLUSION:
      Our findings illustrate important differences between health researchers and
      provide beginning insights into their professional characteristics and engagement
      in Mode I and Mode II activities. A future study designed to examine these
      dimensions in greater detail, including potential covariates across more varied
      institutions, would yield richer insights and enable an examination of relative
      influences, needs and costs of each mode of activity.

PMID- 17204144
TI  - Development of a series of patient information leaflets for constipation using a
      range of cognitive interview techniques: LIFELAX.
AB  - BACKGROUND: The aim of the LIFELAX randomised controlled trial (diet and
      lifestyle vs. laxatives in the management of chronic constipation) is to develop
      and evaluate a cost effective intervention to promote diet and lifestyle in the
      treatment and management of chronic constipation for older people in Primary
      Care. Constipation affects the quality of life in around 20% of older people in
      the community. In the 65 years plus population, a significant proportion of men
      and women both living in institutions (81% and 75% respectively) and free living
      (30% and 37% respectively) use laxatives. Approximately 42 million pounds is
      spent each year on prescribed laxatives in England in addition to laxatives
      purchased over the counter. Although bowel problems are often multifactorial,
      diet and lifestyle have an extremely important role in their management. This
      paper describes one aspect of the main study, the development and piloting of the
      Patient information leaflets (PILs). METHODS: Following review of the literature
      and interviews with practitioners and patients, 8 PILs were designed on:
      constipation, activity, bowel health, fruit and vegetables, fibre, fluid,
      alternative therapies and laxatives. To check the patient's understanding of
      terms used in the PILS and the clarity and accessibility of the information
      understanding, cognitive interviews (CI) were used with nine patients (selected
      from 3 GP surgeries), aged > or = 55 years, who had received > or = 3
      prescriptions of laxatives over 12 months. Interviews were recorded and
      transcribed. RESULTS: Changes made following the CI process included the lay-out,
      words used (e.g. 'exercise' was changed to 'activity', 'gut motility' changed to
      'bowel movement') and descriptions and examples were adapted to be more
      appropriate for the target population. CONCLUSION: Pilot testing with CIs
      resulted in improvements in the PILs, which emphasises the need to pilot PILs
      with the target population before use. The techniques employed are relatively
      inexpensive and could be routinely used when preparing literature for research or
      clinical use including those intended for use with healthcare professionals and
      patients.

PMID- 17204145
TI  - Chicken ovalbumin upstream promoter transcription factor II regulates uncoupling
      protein 3 gene transcription in Phodopus sungorus.
AB  - BACKGROUND: Ucp3 is an integral protein of the inner mitochondrial membrane with
      a role in lipid metabolism preventing deleterious effects of fatty acids in
      states of high lipid oxidation. Ucp3 is expressed in brown adipose tissue and
      skeletal muscle and controlled by a transcription factor complex including
      PPARalpha, MyoD and the histone acetyltransferase p300. Several studies have
      demonstrated interaction of these factors with chicken ovalbumin upstream
      promoter transcription factor II (Coup-TFII). This nuclear receptor is involved
      in organogenesis and other developmental processes including skeletal muscle
      development, but also co-regulates a number of metabolic genes. In this study we
      in silico analyzed the upstream region of Ucp3 of the Djungarian hamster Phodopus
      sungorus and identified several putative response elements for Coup-TFII. We
      therefore investigated whether Coup-TFII is a further player in the
      transcriptional control of the Ucp3 gene in rodents. RESULTS: By quantitative PCR
      we demonstrated a positive correlation of Coup-TFII and Ucp3 mRNA expression in
      skeletal muscle and brown adipose tissue in response to food deprivation and cold
      exposure, respectively. In reporter gene assays Coup-TFII enhanced
      transactivation of the Ucp3 promoter conveyed by MyoD, PPARalpha, RXRalpha and/or
      p300. Using deletions and mutated constructs, we identified a Coup-TFII enhancer
      element 816-840 bp upstream of the transcriptional start site. Binding of Coup
      TFII to this upstream enhancer was confirmed in electrophoretic mobility shift
      and supershift assays. CONCLUSION: Transcriptional regulation of the Coup-TFII
      gene in response to starvation and cold exposure seems to be the regulatory
      mechanism of Ucp3 mRNA expression in brown adipose and skeletal muscle tissue
      determining the final appropriate rate of transcript synthesis. These findings
      add a crucial component to the complex transcriptional machinery controlling
      expression of Ucp3. Given the substantial evidence for a function of Ucp3 in
      lipid metabolism, Coup-TFII may not only be a negative regulator of glucose
      responsive genes but also transactivate genes involved in lipid metabolism.

PMID- 17204146
TI  - Mycoplasma alkalescens demonstrated in bronchoalveolar lavage of cattle in
      Denmark.
AB  - Mycoplasma alkalescens is an arginine-metabolizing mycoplasma, which has been
      found in association with mastitis and arthritis in cattle. Routine
      bacteriological examination of 17 bronchoalveolar lavage samples from calves with
      pneumonia in a single herd in Denmark, identified M. alkalescens in eight
      samples. The organism was found as a sole bacterilogical findings in five of the
      samples as well as in combination with Mannheimia haemolytica, Haemophilus somni
      and Salmonella Dublin. This is the first report of isolation of M. alkalescens in
      Denmark.

PMID- 17204147
TI  - Hereditary chronic pancreatitis.
AB  - Hereditary chronic pancreatitis (HCP) is a very rare form of early onset chronic
      pancreatitis. With the exception of the young age at diagnosis and a slower
      progression, the clinical course, morphological features and laboratory findings
      of HCP do not differ from those of patients with alcoholic chronic pancreatitis.
      As well, diagnostic criteria and treatment of HCP resemble that of chronic
      pancreatitis of other causes. The clinical presentation is highly variable and
      includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic
      function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and
      duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients
      have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen,
      play a causative role in chronic pancreatitis. It has been shown that the PRSS1
      mutations increase autocatalytic conversion of trypsinogen to active trypsin, and
      thus probably cause premature, intrapancreatic trypsinogen activation disturbing
      the intrapancreatic balance of proteases and their inhibitors. Other genes, such
      as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1
      (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) have
      been found to be associated with chronic pancreatitis (idiopathic and hereditary)
      as well. Genetic testing should only be performed in carefully selected patients
      by direct DNA sequencing and antenatal diagnosis should not be encouraged.
      Treatment focuses on enzyme and nutritional supplementation, pain management,
      pancreatic diabetes, and local organ complications, such as pseudocysts, bile
      duct or duodenal obstruction. The disease course and prognosis of patients with
      HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients
      should strongly avoid environmental risk factors for pancreatic cancer.

PMID- 17204148
TI  - Postural development in school children: a cross-sectional study.
AB  - BACKGROUND: Little information on quantitative sagittal plane postural alignment
      and evolution in children exists. The objectives of this study are to document
      the evolution of upright, static, sagittal posture in children and to identify
      possible critical phases of postural evolution (maturation). METHODS: A total of
      1084 children (aged 4-12 years) received a sagittal postural evaluation with the
      Biotonix postural analysis system. Data were retrieved from the Biotonix internet
      database. Children were stratified and analyzed by years of age with n = 36 in
      the youngest age group (4 years) and n = 184 in the oldest age group (12 years).
      Children were analyzed in the neutral upright posture. Variables measured were
      sagittal translation distances in millimeters of: the knee relative to the tarsal
      joint, pelvis relative to the tarsal joint, shoulder relative to the tarsal
      joint, and head relative to the tarsal joint. A two-way factorial ANOVA was used
      to test for age and gender effects on posture, while polynomial trend analyses
      were used to test for increased postural displacements with years of age.
      RESULTS: Two-way ANOVA yielded a significant main effect of age for all 4
      sagittal postural variables and gender for all variables except head translation.
      No age x gender interaction was found. Polynomial trend analyses showed a
      significant linear association between child age and all four postural variables:
      anterior head translation (p < 0.001), anterior shoulder translation (p < 0.001),
      anterior pelvic translation (p < 0.001), anterior knee translation (p < 0.001).
      Between the ages of 11 and 12 years, for anterior knee translation, T-test post
      hoc analysis revealed only one significant rough break in the continuity of the
      age related trend. CONCLUSION: A significant linear trend for increasing sagittal
      plane postural translations of the head, thorax, pelvis, and knee was found as
      children age from 4 years to 12 years. These postural translations provide
      preliminary normative data for the alignment of a child's sagittal plane posture.

PMID- 17204149
TI  - Total and functional parasite specific IgE responses in Plasmodium falciparum
      infected patients exhibiting different clinical status.
AB  - BACKGROUND: There is an increase of serum levels of IgE during Plasmodium
      falciparum infections in individuals living in endemic areas. These IgEs either
      protect against malaria or increase malaria pathogenesis. To get an insight into
      the exact role played by IgE in the outcome of P. falciparum infection, total IgE
      levels and functional anti-parasite IgE response were studied in children and
      adults, from two different endemic areas Gabon and India, exhibiting either
      uncomplicated malaria, severe non cerebral malaria or cerebral malaria, in
      comparison with control individuals. METHODOLOGY AND RESULTS: Blood samples were
      collected from controls and P. falciparum-infected patients before treatment on
      the day of hospitalization (day 0) in India and, in addition, on days 7 and 30
      after treatment in Gabon. Total IgE levels were determined by ELISA and
      functional P. falciparum-specific IgE were estimated using a mast cell line RBL
      2H3 transfected with a human Fcepsilon RI alpha-chain that triggers degranulation
      upon human IgE cross-linking. Mann Whitney and Kruskall Wallis tests were used to
      compare groups and the Spearman test was used for correlations. Total IgE levels
      were confirmed to increase upon infection and differ with level of transmission
      and age but were not directly related to the disease phenotype. All studied
      groups exhibited functional parasite-specific IgEs able to induce mast cell
      degranulation in vitro in the presence of P. falciparum antigens. Plasma IgE
      levels correlated with those of IL-10 in uncomplicated malaria patients from
      Gabon. In Indian patients, plasma IFN-gamma , TNF and IL-10 levels were
      significantly correlated with IgE concentrations in all groups. CONCLUSION:
      Circulating levels of total IgE do not appear to correlate with protection or
      pathology, or with anti-inflammatory cytokine pattern bias during malaria. On the
      contrary, the P. falciparum-specific IgE response seems to contribute to the
      control of parasites, since functional activity was higher in asymptomatic and
      uncomplicated malaria patients than in severe or cerebral malaria groups.

PMID- 17204150
TI  - Contraceptive considerations for breastfeeding women within Jewish law.
AB  - Breast milk has been shown to have multiple benefits to infant health and
      development. Therefore, it is important that maternal contraceptive choices
      consider the effects on lactation. Women who observe traditional Jewish law,
      halakha, have additional considerations in deciding the order of preference of
      contraceptive methods due to religious concerns including the use of barrier and
      spermicidal methods. In addition, uterine bleeding, a common side effect of
      hormonal methods and IUD, can have a major impact on the quality of intimacy and
      marital life due to the laws of niddah. This body of Jewish laws prohibits any
      physical contact from the onset of uterine bleeding until its cessation and for
      an additional week. Health care professionals should understand the issues of
      Jewish law involved in modern contraceptive methods in order to work in tandem
      with the halakha observant woman to choose a contraceptive method that preserves
      the important breastfeeding relationship with her infant and minimizes a negative
      impact on intimacy with her husband.

PMID- 17204151
TI  - VEGF, FGF1, FGF2 and EGF gene polymorphisms and psoriatic arthritis.
AB  - BACKGROUND: Angiogenesis appears to be a first-order event in psoriatic arthritis
      (PsA). Among angiogenic factors, the cytokines vascular endothelial growth factor
      (VEGF), epidermal growth factor (EGF), and fibroblast growth factors 1 and 2
      (FGF1 and FGF2) play a central role in the initiation of angiogenesis. Most of
      these cytokines have been shown to be upregulated in or associated with
      psoriasis, rheumatoid arthritis (RA) or ankylosing spondylitis (AS). As these
      diseases share common susceptibility associations with PsA, investigation of
      these angiogenic factors is warranted. METHODS: Two hundred and fifty-eight
      patients with PsA and 154 ethnically matched controls were genotyped using a
      Sequenom chip-based MALDI-TOF mass spectrometry platform. Four SNPs in the VEGF
      gene, three SNPs in the EGF gene and one SNP each in FGF1 and FGF2 genes were
      evaluated. Statistical analysis was performed using Fisher's exact test, and the
      Cochrane-Armitage trend test. Associations with haplotypes were estimated by
      using weighted logistic models, where the individual haplotype estimates were
      obtained using Phase v2.1. RESULTS: We have observed an increased frequency in
      the T allele of VEGF +936 (rs3025039) in control subjects when compared to our
      PsA patients [Fisher's exact p-value = 0.042; OR 0.653 (95% CI: 0.434, 0.982)].
      Haplotyping of markers revealed no significant associations. CONCLUSION: The T
      allele of VEGF in +936 may act as a protective allele in the development of PsA.
      Further studies regarding the role of pro-angiogenic markers in PsA are
      warranted.

PMID- 17204152
TI  - Identification and analysis of single nucleotide polymorphisms (SNPs) in the
      mosquito Anopheles funestus, malaria vector.
AB  - BACKGROUND: Single nucleotide polymorphisms (SNPs) are the most common source of
      genetic variation in eukaryotic species and have become an important marker for
      genetic studies. The mosquito Anopheles funestus is one of the major malaria
      vectors in Africa and yet, prior to this study, no SNPs have been described for
      this species. Here we report a genome-wide set of SNP markers for use in genetic
      studies on this important human disease vector. RESULTS: DNA fragments from 50
      genes were amplified and sequenced from 21 specimens of An. funestus. A third of
      specimens were field collected in Malawi, a third from a colony of Mozambican
      origin and a third form a colony of Angolan origin. A total of 494 SNPs including
      303 within the coding regions of genes and 5 indels were identified. The physical
      positions of these SNPs in the genome are known. There were on average 7 SNPs per
      kilobase similar to that observed in An. gambiae and Drosophila melanogaster.
      Transitions outnumbered transversions, at a ratio of 2:1. The increased frequency
      of transition substitutions in coding regions is likely due to the structure of
      the genetic code and selective constraints. Synonymous sites within coding
      regions showed a higher polymorphism rate than non-coding introns or 3' and
      5'flanking DNA with most of the substitutions in coding regions being observed at
      the 3rd codon position. A positive correlation in the level of polymorphism was
      observed between coding and non-coding regions within a gene. By genotyping a
      subset of 30 SNPs, we confirmed the validity of the SNPs identified during this
      study. CONCLUSION: This set of SNP markers represents a useful tool for genetic
      studies in An. funestus, and will be useful in identifying candidate genes that
      affect diverse ranges of phenotypes that impact on vector control, such as
      resistance insecticide, mosquito behavior and vector competence.

PMID- 17204154
TI  - GENECODIS: a web-based tool for finding significant concurrent annotations in
      gene lists.
AB  - We present GENECODIS, a web-based tool that integrates different sources of
      information to search for annotations that frequently co-occur in a set of genes
      and rank them by statistical significance. The analysis of concurrent annotations
      provides significant information for the biologic interpretation of high
      throughput experiments and may outperform the results of standard methods for the
      functional analysis of gene lists. GENECODIS is publicly available at
      http://genecodis.dacya.ucm.es/.

PMID- 17204153
TI  - Prostaglandin E2 receptor subtype 2 (EP2) regulates microglial activation and
      associated neurotoxicity induced by aggregated alpha-synuclein.
AB  - BACKGROUND: The pathogenesis of idiopathic Parkinson's disease (PD) remains
      elusive, although evidence has suggested that neuroinflammation characterized by
      activation of resident microglia in the brain may contribute significantly to
      neurodegeneration in PD. It has been demonstrated that aggregated alpha-synuclein
      potently activates microglia and causes neurotoxicity. However, the mechanisms by
      which aggregated alpha-synuclein activates microglia are not understood fully.
      METHODS: We investigated the role of prostaglandin E2 receptor subtype 2 (EP2) in
      alpha-synuclein aggregation-induced microglial activation using ex vivo, in vivo
      and in vitro experimental systems. RESULTS: Results demonstrated that ablation of
      EP2(EP2-/-) significantly enhanced microglia-mediated ex vivo clearance of alpha
      synuclein aggregates (from mesocortex of Lewy body disease patients) while
      significantly attenuating neurotoxicity and extent of alpha-synuclein aggregation
      in mice treated with a parkinsonian toxicant 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine. Furthermore, we report that reduced neurotoxicity by EP2-/-
      microglia could be attributed to suppressed translocation of a critical
      cytoplasmic subunit (p47-phox) of NADPH oxidase (PHOX) to the membranous
      compartment after exposure to aggregated alpha-synuclein. CONCLUSION: Thus, it
      appears that microglial EP2 plays a critical role in alpha-synuclein-mediated
      neurotoxicity.

PMID- 17204155
TI  - FLAME, a novel fuzzy clustering method for the analysis of DNA microarray data.
AB  - BACKGROUND: Data clustering analysis has been extensively applied to extract
      information from gene expression profiles obtained with DNA microarrays. To this
      aim, existing clustering approaches, mainly developed in computer science, have
      been adapted to microarray data analysis. However, previous studies revealed that
      microarray datasets have very diverse structures, some of which may not be
      correctly captured by current clustering methods. We therefore approached the
      problem from a new starting point, and developed a clustering algorithm designed
      to capture dataset-specific structures at the beginning of the process. RESULTS:
      The clustering algorithm is named Fuzzy clustering by Local Approximation of
      MEmbership (FLAME). Distinctive elements of FLAME are: (i) definition of the
      neighborhood of each object (gene or sample) and identification of objects with
      "archetypal" features named Cluster Supporting Objects, around which to construct
      the clusters; (ii) assignment to each object of a fuzzy membership vector
      approximated from the memberships of its neighboring objects, by an iterative
      converging process in which membership spreads from the Cluster Supporting
      Objects through their neighbors. Comparative analysis with K-means, hierarchical,
      fuzzy C-means and fuzzy self-organizing maps (SOM) showed that data partitions
      generated by FLAME are not superimposable to those of other methods and, although
      different types of datasets are better partitioned by different algorithms, FLAME
      displays the best overall performance. FLAME is implemented, together with all
      the above-mentioned algorithms, in a C++ software with graphical interface for
      Linux and Windows, capable of handling very large datasets, named Gene Expression
      Data Analysis Studio (GEDAS), freely available under GNU General Public License.
      CONCLUSION: The FLAME algorithm has intrinsic advantages, such as the ability to
      capture non-linear relationships and non-globular clusters, the automated
      definition of the number of clusters, and the identification of cluster outliers,
      i.e. genes that are not assigned to any cluster. As a result, clusters are more
      internally homogeneous and more diverse from each other, and provide better
      partitioning of biological functions. The clustering algorithm can be easily
      extended to applications different from gene expression analysis.

PMID- 17204156
TI  - Prevalence and factors associated with alcohol and drug-related disorders in
      prison: a French national study.
AB  - BACKGROUND: Most studies measuring substance-use disorders in prisons focus on
      incoming or on remand prisoners and are generally restricted to drugs. However,
      there is evidence that substance use initiation or continuation occurs in prison,
      and that alcohol use is common. The aim of this study is 1) to assess prevalence
      of both drug and alcohol abuse and dependence (DAD/AAD) in a national randomised
      cohort of French prisoners, short or long-term sentence 2) to assess the risk
      factors associated with DAD/AAD in prison. a stratified random strategy was used
      to select 1) 23 prisons among the different types of prison 2) 998 prisoners.
      Diagnoses were assessed according to a standardized procedure, each prisoner
      being assessed by two psychiatrists, one junior, using a structured interview
      (MINI 5 plus), and one senior, completing the procedure with an open clinical
      interview. At the end of the interview the clinicians met and agreed on a list of
      diagnoses. Cloninger's Temperament and Character Inventory (TCI) was also used.
      RESULTS: More than a third of prisoners presented either AAD or DAD in the last
      12 months. Cannabis was the most frequent drug and just under a fifth of
      prisoners had AAD. AAD and DAD were clearly different for the following: socio
      demographic variables, childhood history, imprisonment characteristics,
      psychiatric comorbidity and Cloninger's TCI. Profiles of AAD in prison are
      similar to type II alcoholism. CONCLUSION: Regular screening of AAD/DAD in
      prison, and specific treatment programmes taking into account differences between
      prisoners with an AAD and prisoners with a DAD should be a public health priority
      in prison.

PMID- 17204157
TI  - Magnetic characterization of superparamagnetic nanoparticles pulled through model
      membranes.
AB  - BACKGROUND: To quantitatively compare in-vitro and in vivo membrane transport
      studies of targeted delivery, one needs characterization of the magnetically
      induced mobility of superparamagnetic iron oxide nanoparticles (SPION). Flux
      densities, gradients, and nanoparticle properties were measured in order to
      quantify the magnetic force on the SPION in both an artificial cochlear round
      window membrane (RWM) model and the guinea pig RWM. METHODS: Three-dimensional
      maps were created for flux density and magnetic gradient produced by a 24-well
      casing of 4.1 kilo-Gauss neodymium-iron-boron (NdFeB) disc magnets. The casing
      was used to pull SPION through a three-layer cell culture RWM model. Similar maps
      were created for a 4 inch (10.16 cm) cube 48 MGOe NdFeB magnet used to pull
      polymeric-nanoparticles through the RWM of anesthetized guinea pigs. Other
      parameters needed to compute magnetic force were nanoparticle and polymer
      properties, including average radius, density, magnetic susceptibility, and
      volume fraction of magnetite. RESULTS: A minimum force of 5.04 x 10(-16) N was
      determined to adequately pull nanoparticles through the in-vitro model. For the
      guinea pig RWM, the magnetic force on the polymeric nanoparticles was 9.69 x 10
      20 N. Electron microscopy confirmed the movement of the particles through both
      RWM models. CONCLUSION: As prospective carriers of therapeutic substances,
      polymers containing superparamagnetic iron oxide nanoparticles were succesfully
      pulled through the live RWM. The force required to achieve in vivo transport was
      significantly lower than that required to pull nanoparticles through the in-vitro
      RWM model. Indeed very little force was required to accomplish measurable
      delivery of polymeric-SPION composite nanoparticles across the RWM, suggesting
      that therapeutic delivery to the inner ear by SPION is feasible.

PMID- 17204158
TI  - An annotated catalogue of salivary gland transcripts in the adult female
      mosquito, Aedes aegypti.
AB  - BACKGROUND: Saliva of blood-sucking arthropods contains a cocktail of
      antihemostatic agents and immunomodulators that help blood feeding. Mosquitoes
      additionally feed on sugar meals and have specialized regions of their glands
      containing glycosidases and antimicrobials that might help control bacterial
      growth in the ingested meals. To expand our knowledge on the salivary cocktail of
      AEdes aegypti, a vector of dengue and yellow fevers, we analyzed a set of 4,232
      expressed sequence tags from cDNA libraries of adult female mosquitoes. RESULTS:
      A nonredundant catalogue of 614 transcripts (573 of which are novel) is
      described, including 136 coding for proteins of a putative secretory nature.
      Additionally, a two-dimensional gel electrophoresis of salivary gland (SG)
      homogenates followed by tryptic digestion of selected protein bands and MS/MS
      analysis revealed the expression of 24 proteins. Analysis of tissue-specific
      transcription of a subset of these genes revealed at least 31 genes whose
      expression is specific or enriched in female SG, whereas 24 additional genes were
      expressed in female SG and in males but not in other female tissues. Most of the
      55 proteins coded by these SG transcripts have no known function and represent
      high-priority candidates for expression and functional analysis as antihemostatic
      or antimicrobial agents. An unexpected finding is the occurrence of four protein
      families specific to SG that were probably a product of horizontal transfer from
      prokaryotic organisms to mosquitoes. CONCLUSION: Overall, this paper contributes
      to the novel identification of 573 new transcripts, or near 3% of the AE. aegypti
      proteome assuming a 20,000-protein set, and to the best-described sialome of any
      blood-feeding insect.

PMID- 17204160
TI  - Psychogenic or neurogenic origin of agrammatism and foreign accent syndrome in a
      bipolar patient: a case report.
AB  - BACKGROUND: Foreign accent syndrome (FAS) is a rare speech disorder characterized
      by the appearance of a new accent, different from the speaker's native language
      and perceived as foreign by the speaker and the listener. In most of the reported
      cases, FAS follows stroke but has also been found following traumatic brain
      injury, cerebral haemorrhage and multiple sclerosis. In very few cases, FAS was
      reported in patients presenting with psychiatric disorders but the link between
      this condition and FAS was confirmed in only one case. CASE PRESENTATION: In this
      report, we present the case of FG, a bipolar patient presenting with language
      disorders characterized by a foreign accent and agrammatism, initially
      categorized as being of psychogenic origin. The patient had an extensive
      neuropsychological and language evaluation as well as brain imaging exams. In
      addition to FAS and agrammatism, FG also showed a working memory deficit and
      executive dysfunction. Moreover, these clinical signs were related to altered
      cerebral activity on an FDG-PET scan that showed diffuse hypometabolism in the
      frontal, parietal and temporal lobes bilaterally as well as a focal deficit in
      the area of the anterior left temporal lobe. When compared to the MRI, these
      deficits were related to asymmetric atrophy, which was retrospectively seen in
      the left temporal and frontal opercular/insular region without a focal lesion.
      DISCUSSION: To our knowledge, FG is the first case of FAS imaged with an 18F-FDG
      PET scan. The nature and type of neuropsychological and linguistic deficits,
      supported by neuroimaging data, exclude a neurotoxic or neurodegenerative origin
      for this patient's clinical manifestations. For similar reasons, a psychogenic
      etiology is also highly improbable. CONCLUSION: To account for the FAS and
      agrammatism in FG, various explanations have been ruled out. Because of the focal
      deficit seen on the brain imaging, involving the left insular and anterior
      temporal cortex, two brain regions frequently involved in aphasic syndrome but
      also in FAS, a cerebrovascular origin must be considered the best explanation to
      account for FG's language deficits.

PMID- 17204159
TI  - Quantitative analysis of Nipah virus proteins released as virus-like particles
      reveals central role for the matrix protein.
AB  - BACKGROUND: Nipah virus (NiV) is an emerging paramyxovirus distinguished by its
      ability to cause fatal disease in both animal and human hosts. Together with
      Hendra virus (HeV), they comprise the genus Henipavirus in the Paramyxoviridae
      family. NiV and HeV are also restricted to Biosafety Level-4 containment and this
      has hampered progress towards examining details of their replication and
      morphogenesis. Here, we have established recombinant expression systems to study
      NiV particle assembly and budding through the formation of virus-like particles
      (VLPs). RESULTS: When expressed by recombinant Modified Vaccinia virus Ankara
      (rMVA) or plasmid transfection, individual NiV matrix (M), fusion (F) and
      attachment (G) proteins were all released into culture supernatants in a membrane
      associated state as determined by sucrose density gradient flotation and
      immunoprecipitation. However, co-expression of F and G along with M revealed a
      shift in their distribution across the gradient, indicating association with M in
      VLPs. Protein release was also altered depending on the context of viral proteins
      being expressed, with F, G and nucleocapsid (N) protein reducing M release, and N
      release dependent on the co-expression of M. Immunoelectron microscopy and
      density analysis revealed VLPs that were similar to authentic virus. Differences
      in the budding dynamics of NiV proteins were also noted between rMVA and plasmid
      based strategies, suggesting that over-expression by poxvirus may not be
      appropriate for studying the details of recombinant virus particle assembly and
      release. CONCLUSION: Taken together, the results indicate that NiV M, F, and G
      each possess some ability to bud from expressing cells, and that co-expression of
      these viral proteins results in a more organized budding process with M playing a
      central role. These findings will aid our understanding of paramyxovirus particle
      assembly in general and could help facilitate the development of a novel vaccine
      approach for henipaviruses.

PMID- 17204161
TI  - Dietary calcium intake and renin angiotensin system polymorphisms alter the blood
      pressure response to aerobic exercise: a randomized control design.
AB  - BACKGROUND: Dietary calcium intake and the renin angiotensin system (RAS)
      regulate blood pressure (BP) by modulating calcium homeostasis. Despite similar
      BP regulatory effects, the influence of dietary calcium intake alone and combined
      with RAS polymorphisms on the BP response following acute aerobic exercise (i.e.,
      postexercise hypotension) has not been studied. Thus, we examined the effect of
      dietary calcium intake and selected RAS polymorphisms on postexercise
      hypotension. METHODS: Subjects were men (n = 50, 43.8 +/- 1.3 yr) with high BP
      (145.3 +/- 1.5/85.9 +/- 1.1 mm Hg). They completed three experiments: non
      exercise control and two cycle bouts at 40% and 60% of maximal oxygen consumption
      (VO2max). Subjects provided 3 d food records on five protocol-specific occasions.
      Dietary calcium intake was averaged and categorized as low (<880 mg/d = LowCa) or
      high (> or = 880 mg/d = HighCa). RAS polymorphisms (angiotensin converting enzyme
      insertion/deletion, ACE I/D; angiotensin II type 1 receptor, AT1R A/C) were
      analyzed with molecular methods. Genotypes were reduced from three to two: ACE
      II/ID and ACE DD; or AT1R AA and AT1R CC/AC. Repeated measure ANCOVA tested if BP
      differed among experiments, dietary calcium intake level and RAS polymorphisms.
      RESULTS: Systolic BP (SBP) decreased 6 mm Hg after 40% and 60% VO2max compared to
      non-exercise control for 10 h with LowCa (p < 0.01), but not with HighCa (p > or
      = 0.05). Under these conditions, diastolic BP (DBP) did not differ between
      dietary calcium intake levels (p > or = 0.05). With LowCa, SBP decreased after
      60% VO2max versus non-exercise control for 10 h among ACE II/ID (6 mm Hg) and
      AT1R AA (8 mm Hg); and by 8 mm Hg after 40% VO2max among ACE DD and AT1R CC/CA (p
      < 0.01). With HighCa, SBP (8 mm Hg) and DBP (4 mm Hg) decreased after 60% VO2max
      compared to non-exercise control for 10 h (p < 0.05), but not after 40% VO2max (p
      > or = 0.05). CONCLUSION: SBP decreased after exercise compared to non-exercise
      control among men with low but not high dietary calcium intake. Dietary calcium
      intake interacted with the ACE I/D and AT1R A/C polymorphisms to further modulate
      postexercise hypotension. Interactions among dietary calcium intake, exercise
      intensity and RAS polymorphisms account for some of the variability in the BP
      response to exercise.

PMID- 17204162
TI  - Rates of inappropriate antiretroviral prescription among injection drug users.
AB  - BACKGROUND: Although the survival benefits of antiretroviral therapy (ART) for
      the treatment of HIV infection are well established, the clinical management of
      HIV disease continues to present major challenges. There are particular concerns
      regarding access to appropriate HIV treatment among HIV-infected injection drug
      users (IDU). METHODS: In a prospective cohort study of HIV-infected IDU in
      Vancouver, Canada, we examined initial ART regimens vis-a-vis the provincial
      government's therapeutic guidelines at the time ART was initiated. Briefly, there
      have been four sets of guidelines: Era 1 (1992 to November 1995; double-drug
      (dual NRTIs) ART for patients with a CD4 cell count of 350 or less); Era 2
      (December 1995 to May 1996; double-drug therapy for patients with a CD4+ cell
      count of 500 or less); Era 3 (June 1996 to June 1997; triple-drug therapy (dual
      NRTIs with a PI or NNRTI) for patients who had a plasma viral load of > 100,000
      HIV-1 RNA copies/mL; dual therapy with two NRTIs for those with a plasma viral
      load of 5,000 to 100,000 HIV-1 RNA copies/mL); Era 4 (since July 1997; universal
      use of triple drug therapy as first-line treatment). RESULTS: Between May 1996
      and May 2003, 431 HIV-infected individuals were enrolled into the cohort. By May
      31, 2003, 291 (67.5%) individuals had initiated ART. We noted instances of
      inappropriate antiretroviral prescription in each guideline era, with 9 (53%) in
      Era 1, 3 (12%) in Era 2, 22 (28%) in Era 3, and 23 (15%) in Era 4. Of the 57
      subjects who received an inappropriate ART regimen initially, 14 never received
      the appropriate therapy; among the remaining 43, the median time to the
      initiation of a guideline-appropriate ART regimen was 12 months (inter-quartile
      range 5-20). CONCLUSION: The present study identified measurable rates of
      guideline-inappropriate ART prescription for patients who were injection drug
      users. Rates were highest in the era of dual therapy, although high rates
      persisted into the triple-therapy era. As therapeutic guidelines continue to
      evolve, it is critical that mechanisms be put in place to ensure prescription of
      ART combinations for IDU that are consistent with current expert recommendations.

PMID- 17204163
TI  - Clustering of genes into regulons using integrated modeling-COGRIM.
AB  - We present a Bayesian hierarchical model and Gibbs Sampling implementation that
      integrates gene expression, ChIP binding, and transcription factor motif data in
      a principled and robust fashion. COGRIM was applied to both unicellular and
      mammalian organisms under different scenarios of available data. In these
      applications, we demonstrate the ability to predict gene-transcription factor
      interactions with reduced numbers of false-positive findings and to make
      predictions beyond what is obtained when single types of data are considered.

PMID- 17204164
TI  - Recombinant Escherichia coli produces tailor-made biopolyester granules for
      applications in fluorescence activated cell sorting: functional display of the
      mouse interleukin-2 and myelin oligodendrocyte glycoprotein.
AB  - BACKGROUND: Fluorescence activated cell sorting (FACS) is a powerful technique
      for the qualitative and quantitative detection of biomolecules used widely in
      both basic research and clinical diagnostic applications. Beads displaying a
      specific antigen are used to bind antibodies which are then fluorescently
      labelled using secondary antibodies. As the individual suspension bead passes
      through the sensing region of the FACS machine, fluorescent signals are acquired
      and analysed. Currently, antigens are tediously purified and chemically cross
      linked to preformed beads. Purification and coupling of proteins often renders
      them inactive and they will not be displayed in its native configuration. As an
      alternative, we genetically engineered Escherichia coli to produce biopolyester
      (polyhdroxyalkanoate=PHA) granules displaying diagnostically relevant antigens in
      their native conformation and suitable for FACS analysis. RESULTS: Hybrid genes
      were constructed, which encode either the mouse interleukin-2 (IL2) or the myelin
      oligodendrocyte glycoprotein (MOG) fused via an enterokinase site providing
      linker region to the C terminus of the PHA granule associated protein PhaP,
      respectively. The hybrid genes were expressed in PHA-accumulating recombinant E.
      coli. MOG and IL2 fusion proteins were abundantly attached to PHA granules and
      were identified by MALDI-TOF/MS analysis and N terminal sequencing. A more
      abundant second fusion protein of either MOG or IL2 resulted from an additional N
      terminal fusion, which did surprisingly not interfere with attachment to PHA
      granule. PHA granules displaying either IL2 or MOG were used for FACS using
      monoclonal anti-IL2 or anti-MOG antibodies conjugated to a fluorescent dye. FACS
      analysis showed significant and specific binding of respective antibodies.
      Enterokinase treatment of IL2 displaying PHA granules enabled removal of IL2 as
      monitored by FACS analysis. Mice were immunized with either MOG or OVA
      (ovalbumin) and the respective sera were analysed using MOG-displaying PHA
      granules and FACS analysis showing a specific and sensitive detection of antigen
      specific antibodies within a wide dynamic range. CONCLUSION: E. coli can be
      genetically engineered to produce PHA granules displaying correctly folded
      eukaryotic proteins and which can be applied as beads in FACS based diagnostics.
      Since PHA granule formation and protein attachment occurs in one step already
      inside the bacterial cell, microbial production could be a cheap and efficient
      alternative to commercial beads.

PMID- 17204165
TI  - Fixed or mobile-bearing total knee arthroplasty.
AB  - Fixed and mobile-bearing in total knee arthroplasty are still discussed
      controversially. In this article, biomechanical and clinical aspects in both
      fixed and mobile-bearing designs were reviewed. In biomechanical aspect, the
      mobile-bearing design has proved to provide less tibiofemoral contact stresses
      under tibiofemoral malalignment conditions. It also provides less wear rate in in
      vitro simulator test. Patients with posterior stabilized mobile-bearing knees had
      more axial tibiofemoral rotation than patients with posterior stabilized fixed
      bearing knees during gait as well as in a deep knee-bend activity. However, in
      clinical aspect, the mid-term or long-term survivorship of mobile-bearing knees
      has no superiority over that of fixed-bearing knees. The theoretical advantages
      for mobile-bearing design to provide a long-term durability have not been
      demonstrated by any outcome studies. Finally, the fixed-bearing design with all
      polyethylene tibial component is suggested for relatively inactive, elder people.
      The mobile-bearing design is suggested for younger or higher-demand patients due
      to the potential for reduced polyethylene wear and more normal kinematics
      response after joint replacement. For younger surgeon, the fixed-bearing design
      is suggested due to less demand for surgical technique. For experienced surgeon,
      one familiar surgical protocol and instrumentation is suggested rather than
      implant design, either fixed-bearing or mobile-bearing.

PMID- 17204166
TI  - [A new method for 5, 10-methylenetetrahydrofolate reductase single nucleotide
      polymorphisms genotyping used to study susceptibility of hematological
      malignancy].
AB  - The aim of this study was to set up a new method for 5, 10
      Methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms (SNP)
      genotyping, and to investigate the hereditary susceptibility of hematological
      malignancy. Prepared an aimed gene microarray based on cDNA microarray theory,
      dual-color fluorescence hybridization was used to detect SNP loci, and DNA
      sequencing was performed to confirm the results. The MTHFR C677T SNP loci of 157
      controls and 127 patients with hematological malignancies (30 multiple myeloma,
      28 non-Hodgkin's lymphoma, 22 acute lymphoblastic leukemia, 40 acute myeloid
      leukemia, 7 chronic myeloid leukemia) from Jiangsu province were detected. The
      results showed that after overlapping, homozygous wild type, heterozygote type
      and homozygous mutant type yielded green, yellow and red fluorescence,
      respectively. DNA sequencing validated these results. The allele frequency of
      677C and 677T in patients and controls were 58.7% and 66.9%, 41.3% and 33.1%
      respectively, showing statistically significant difference (chi2 = 4.077, P =
      0.043). 677TT genotype showed a significantly higher risk of MM (OR = 4.21; 95%
      CI = 1.50 - 11.83; P = 0.006). It is concluded that this microarray-based method
      is accurate, high-throughput and inexpensive, suitable for SNP genotyping in a
      large number of individuals. C677T polymorphisms influence the risk of
      hematological malignancies. 677TT genotype is susceptive to MM.

PMID- 17204167
TI  - [Karyotype analysis in 119 patients with chronic myeloid leukemia at blast
      crisis].
AB  - To investigate the karyotype of chronic myeloid leukemia in blast crisis (CML
      BC), karyotype analysis was performed with R-banding technique in 119 patients
      with CML-BC. Dual fusion fluorescence in situ hybridization (FISH) was used to
      detect derivative chromosome 9 deletions in randomly selected 28 cases of them.
      The results showed that 11 cases (8.9%) were Ph negative; 113 cases (91.1%) were
      Ph positive; 104 cases (83.9%) had standard Ph translocation; 9 cases (7.2%)
      showed variant translocation, including 4 cases (3.2%) with simple variant
      translocation and 5 cases (4.0%) with complex variant translocation. 72.6% of Ph
      negative CML-BC had extra chromosomal abnormalities, with the most common ones
      being i (17q) and +14. 72.3% of Ph positive CML-BC had extra cytogenetic changes
      and +Ph, +8, i (17q) were the most frequent. The average time between diagnosis
      and blast crisis was 29.0 months (range 2 to 66 months) for Ph negative cases and
      34.2 months (range 1 to 127 months) for Ph positive cases. 5 cases (5/28, 17.9%)
      with der (9) deletions were detected by FISH technique. It is concluded that
      extra chromosomal abnormalities are common in CML-BC patients and FISH can
      effectively detect the der (9) deletions.

PMID- 17204168
TI  - Comparison of immunophenotype and clinical manifestations between patients with
      M5a and M5b of acute monocytic leukemia.
AB  - Acute monocytic leukemia is a distinct subtype of acute myeloid leukemia (AML)
      with characteristic biology and clinical features. This study was designed to
      compare the immunophenotypical features and clinical manifestations of the
      patients with AML-M(5a) to that of patients with AML-M(5b), and to identify
      differences between M(5a) and M(5b) and to explore their relations. A total of 58
      cases of de novo adult patients with AML M(5) were investigated.
      Immunofluorescence analysis by flow cytometry was performed to determine the
      immunophenotype of the leukemic cells in all cases. Meanwhile, clinical data of
      these cases were studied retrospectively. The results showed that the
      immunophenotypes of monocytic leukemic cells in patients with AML M(5) were
      heterogeneous, and CD68 and CD11b were expressed higher in patients with AML
      M(5a), compared with that in patients with AML M(5b) (P < 0.01). The significant
      differences in sex, extramedullary infiltration, WBC counts of peripheral blood,
      complete remission rate and disease-free survival (DFS > 300 days) between the
      patients with AML M(5a) and M(5b) did not exist (P > 0.05). It is concluded that
      the special individual immunophenotype features can be detected in patients with
      either of AML M(5a) or M(5b), and that expressions of CD68 and CD11b were much
      higher in M(5a). It seems that the complete remission rate and disease-free
      survival of patients with M(5a) and M(5b) are not different from that of
      currently available therapy.

PMID- 17204169
TI  - [Effect of the new human transcription factor hBKLF on the proliferation,
      differentiation of K562 cell line and hemoglobin synthesis].
AB  - The human basic Kruppel-like factor (hBKLF) is a newly cloned human transcription
      factor from the cDNA library of fetal liver. It belongs to the Kruppel-like
      transcription factor family. Previous expression study showed that it is a
      hematopoietic related factor. This study was aimed to investigate the effect of
      hBKLF on cell proliferation, differentiation and hemoglobin synthesis by using
      K562 cell line as model. The sense and antisense expression plasmids of hBKLF
      were constructed, and transfected into K562 cells by lipofectamine. After G418
      selection for 4 weeks, the cell line with stable expression of the gene was
      obtained. Then the hBKLF expression level, proliferation ability, colony
      formation and hemoglobin production were detected by RT-PCR and Western blot, MTT
      method, methyl cellulose semisolid culture method and benzidine test
      respectively. The morphologic change of cell was observed with inverted
      microscope. The results showed that the sense plasmid could increase hBKLF level
      and antisense plasmid could decrease hBKLF expression. When hBKLF level was down
      regulated, K562 cells could proliferate more quickly and synthesize more
      hemoglobin. But there were no differences in colony formation ability and no
      apparent morphologic change. It is concluded that hBKLF can inhibit hematopoietic
      cell proliferation and hemoglobin synthesis. It is suggested that hBKLF plays an
      important role in the proliferation and differentiation of hematopoietic cells.

PMID- 17204170
TI  - Effect of ginseng saponin, arsenic trioxide, beta-elemene combined with CTX on
      telomere-telomerase system in K562 cell line.
AB  - This study was aimed to investigate the modulating effects on telomere length and
      telomerase activity in K562 cells treated by arsenic trioxide, ginseng saponin,
      beta-elemene alone or in combination with cyclophosphamide (CTX) and to explore
      the possible mechanism and new therapy for acute leukemia. Human erythroleukemic
      cell line K562 was co-cultured with the above-mentioned drugs. Cells were
      collected after 24, 48 and 72 hours for further detection. Telomere length and
      telomerase activity were detected by Southern-blot and PCR-ELISA respectively.
      The effects of these drugs were observed at different concentrations and exposure
      time. The results showed that (1) ginseng saponin, arsenic trioxide, beta
      elemene, or CTX could completely inhibit the telomerase activity of K562 cells at
      proper concentrations and exposure time. The inhibiting effects were enhanced
      when the three former drugs were used with CTX. Telomerase activity decreased
      proportionally with the concentrations and length of time. (2) viability of K562
      cells was decreased after being co-cultured with arsenic trioxide, ginseng
      saponin, beta-elemene and CTX. The level of inhibition depends on the
      concentration and exposure time. (3) telomere length of K562 cells was 5.36 +/-
      0.18 kb. After being co-cultured with those drugs for 72 hours, telomere length
      was 5.90 kb -6.50 kb, significantly longer than that of control (5.18 - 5.35 kb).
      It is concluded that arsenic trioxide, ginseng saponin, and beta-elemene can
      inhibit the growth and telomerase activity of K562 cells. The inhibiting effects
      were enhanced when they were used in combination with CTX. The depression of
      telomerase activity may be one of the mechanisms of anti-tumor effect. Less
      dosage and shorter course can be expected when arsenic trioxide, ginseng saponin,
      and beta-elemene are used in combination with CTX. When telomerase activity was
      depressed, the telomere length prolonged a little, indicating K562 cell line may
      extend telomeres by some alternative way other than telomerase activation.

PMID- 17204171
TI  - [Aberrant localization of beta-catenin in leukemia cell lines].
AB  - Beta-catenin plays a central role in Wnt signaling pathway. The aberrant
      localization of beta-catenin in nucleus causes the transcription of down-stream
      target genes, which is the pathogenesy of some solid tumours. As the expression
      of adheren junction on hemopoietic cells is very low, there are a few studies on
      beta-catenin expression in leukaemia. This study was aimed to investigate beta
      catenin localization and beta-catenin mRNA expression levels in 4 leukemia cell
      lines so as to explore a new oncogenic mechanism and to find out a new
      therapeutic target. The beta-catenin localization in leukemia cell lines was
      detected by immunocytochemistry, the beta-catenin mRNA expression level was
      assayed by real-time quantitative RT-PCR. The results showed that there was
      aberrant localization of beta-catenin in Jurkat and Thp-1, and beta-catenin mRNA
      expression level was not increased in these two cell lines, however, the mRNA
      expression levels of Jurkat and Thp-1 were lower than those of Daudi and K562.
      The beta-catenin mRNA expression level was not correlated with beta-catenin
      aberrant localization in these 4 cell lines. It is concluded that the aberrant
      localization of beta-catenin may play a role in the development of some leukemia,
      and the mechanism resulting in beta-catenin aberrant localization not take place
      at transcription level.

PMID- 17204172
TI  - [Detection of IgVH mutation status in patients with chronic lymphocytic leukemia
      by multiplex PCR].
AB  - IgVH mutation status is one of the most important independent prognostic factor
      of chronic lymphocytic leukemia (CLL). In order to evaluate IgVH mutation status
      in patients with CLL, IgVH mutation was detected by multiplex PCR in 9 CLL
      patients and purified PCR amplification products were directly sequenced, IgH
      somatic hypermutation and mutation site were analysed by IMGT/V-QUEST. The
      results showed that 5 patients had mutated IgVH, and IgVHs were IGHV3-11*03,
      IGHV3-9*01, IGHV3-23*01, IGHV4-59*01, IGHV4-34*02, respectively; whereas 4 others
      had unmutated IgVH, these IgVHs were IGHV3-53*01, IGHV3-23*03, IGHV3-33*05 and
      IGHV3-7*01. It is concluded that multiplex PCR is a rapid and easy method to
      detect IgVH mutation status, and it solves the limitations and pitfalls of
      routine PCR, and it is worth being extensively used both in clinic and scientific
      researches.

PMID- 17204173
TI  - [Mechanism of G2/M blockage triggered by activated-Chk1 in regulation of drug
      resistance in K562/A02 cell line].
AB  - The study was purposed to investigate the effect of phosphorylated-chk1 on cell
      cycle and apoptosis of human erythroleukemic cell line K562 and K562/A02, and to
      explore the mechanism of chk1 in regulation of drug-resistance of leukemia cells.
      After treatment with adrimycin for six hours, the cell cycle distribution was
      detected by flow cytometry; the Chk1mRNA expression was detected by RT-PCR and
      the Chk1 phosphorylation level was detected by Western blot. Under the condition
      of down-regulation of Chk1mRNA expression in cells transfected with Chk1 short
      hairpin RNA, the cell apoptosis rates were detected by flow-cytometry following
      adrimycin. The results indicated that the proportion of K562/A02 cell line in
      G2/M phase was (54.12 +/- 0.57)% at 6 hours after drug treatment, significantly
      higher than that of K562 cell line (36.99 +/- 1.28)%. No evident difference of
      the Chk1mRNA expression was observed between K562 and K562/A02 cell lines, while
      elevated Chk1 phosphorylation following DNA damage induced by adriamycin was
      observed in the K562/A02 cell line (0.79 +/- 0.56), significantly higher than
      that in K562 cell line (0.27 +/- 1.47). The cell apoptosis rate of the Chk1 shRNA
      group in K562/A02 cell line was 3.84-fold of blank vector group, but that in K562
      cell line was 1.30-fold of blank vector group. It is concluded that the increased
      chk1 activity that delay the progress of cell cycle are associated with cellular
      resistance to adrimycin in the K562/A02 cell line.

PMID- 17204174
TI  - [Drug resistance reversal of HL-60/ADR cells by simultaneous suppression of XIAP
      and MRP].
AB  - This study was purposed to explore the mechanisms of drug resistance of HL-60/ADR
      cells and to compare the reversal drug-resistance effects of antisense
      oligonucleotides (AS ODN) of XIAP (X-linked inhibitor of apoptosis protein) and
      AS ODNs of MRP (multidrug resistance-associated protein) by use alone or in
      combination. Reverse transcription-PCR and Western blot were applied to detect
      the expression of XIAP, BCL-2, MRP and MDR1 in mRNA and protein levels of HL-60
      cells and HL-60/ADR cells, respectively. Fully phosphorothioated AS ODN of XIAP
      and MRP was delivered into HL-60/ADR cells with Lipofectamine 2000 in the form of
      liposome-ODN complexes alone or in combination. CCK-8 cell viability assay was
      used to determine the effect of AS ODN of XIAP and MRP used alone or in
      combination on the chemotherapy sensitivity of HL-60/ADR cells to daunorubicin
      (DNR). Reverse transcription-PCR and Western blot were applied to examine the
      changes of XIAP, MRP in mRNA and protein levels respectively. The results showed
      that MRP and XIAP were both significantly higher in HL-60/ADR cells than those in
      HL-60 cells. AS ODN of XIAP and MRP down-regulated the expression of XIAP and MRP
      in HL-60/ADR cells and increased the sensitivity of HL-60/ADR cells to DNR,
      respectively. AS ODN of XIAP + MRP did not enhance the inhibition expression of
      XIAP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR
      significantly as compared with AS ODN of XIAP (P < 0.05). AS ODN of XIAP + MRP
      did not increase the concentration of DNR nor enhanced the inhibition expression
      of MRP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR
      significantly (P < 0.05), as compared with AS ODN of MRP. It is concluded that
      both XIAP and MRP may be involved in the drug resistance mechanisms of HL-60/ADR
      cells. Drug-resistance of HL-60/ADR cells can be reversed significantly when
      antisense oligonucleotides of XIAP and MRP were used in combination.

PMID- 17204175
TI  - [Apoptosis of K562 cells induced by nociceptin/orphanin FQ].
AB  - The study was to investigate the proliferation and apoptosis effect of
      nociceptin/orphanin FQ (OFQ) on 562 cells in vitro. Inhibition of K562 cells
      proliferation was measured by MTT assay. Morphological assessment of apoptosis
      was performed with Wright staining and transmission electron microscope. The
      apoptosis peak was measured by flow cytometry. DNA fragmentation was visualized
      by agarose gel electrophoresis. The results showed that OFQ time-dependently and
      no-dose-dependently inhibited the proliferation of K562 cells at concentrations
      of 10(-6) - 10(-13) mol/L. Discrete maximum of cytolytic activity was detected at
      concentrations of 10(-6) - 10(-7), 10(-9), 10(-12) mol/L. Compared with the
      control group K562 cells, the cells treated with OFQ at concentration of 10(-9)
      mol/L for 72 hours showed typical characteristics of apoptosis under transmission
      electron microscope. Apoptosis peak was found by FCM at concentration of 0, 10(
      7), 10(-8), 10(-9) mol/L of OFQ for 72 hours, apoptosis rates were 0%, 22.8%,
      23.8% and 26.5% respectively. DNA agarose gel electrophoresis revealed nuclear
      fragmentation (DNA ladder). It is concluded that OFQ can inhibit the
      proliferation of K562 cells and induce the apoptosis in K562 cells.

PMID- 17204176
TI  - [Proliferation inhibition and apoptosis induction of K562 cells by D-limonene].
AB  - This study was aimed to investigate the effect of D-limonene on K562 leukemia
      cells and its mechanism. Inhibitory effect of D-limonene on proliferation of K562
      leukemia cells was assayed by MTT method and cell apoptosis was detected by flow
      cytometry and DNA agarose gel electrophoresis, the morphologic change of K562
      cells was observed by microscopy. The results showed that when K562 cells were
      treated with 0.125 - 1.0 mmol/L of D-limonene for 48 hours, the proliferation of
      K562 cells was obviously inhibited in dose-dependent manner. Typical
      morphological changes and the typical DNA ladder on agarose gel electrophoresis
      for analysis of cellular apoptosis were significantly appeared in D-limonene
      treated K562 cells. Simultaneously, the sub-G1 peak was found in FCM analysis. It
      is concluded that the D-limonene can inhibit proliferation of K562 cells in dose
      dependent manner, cause cell detained at G1 phase and induce apoptosis of K562
      cells.

PMID- 17204177
TI  - [Combined effect of recombinant mutant human TRAIL and daunorubicin in inducing
      apoptosis of leukemia cell and its mechanism].
AB  - The aim of study was to investigate the combined effect of recombinant mutant
      human TRAIL (rmhTRAIL) with daunorubicin (DNR) or alone on K562 and U937 leukemia
      cell lines and its mechanism. The fibroblasts (MRC-5) of normal-human embryonic
      lung were used as control cells. After being treated with rmhTRAIL and DNR or
      only with rmTRAIL, the cytotoxic effect and the apoptosis rate in K562, U937
      cells were measured by MTT assay. The expression levels of TRAIL death receptor
      and TRAIL decoy receptor mRNA in these three cell lines were assayed by
      semiquantitive RT-PCR before and after treatment with DNR. The results indicated
      that K562 and U937 were sensitive to rmhTRIAL. DNR had synergistic inhibitory
      effect with rmhTRAIL on the growth of K562 and U937 cell lines (P < 0.05). The
      expression level of DR4 and DR5 mRNA was significantly higher in K562 and U937
      with combined treatment of rmhTRAIL and DNR than that in those alone, while the
      expressions of DcR1 and DcR2 mRNA were not influenced. It is concluded that in
      vitro, rmhTRAIL alone or in combination with DNR can obviously inhibit the growth
      of leukemia cell lines and induce cell apoptosis, DNR and rmhTRAIL have a
      synergistic inhibitory effect on growth of K562 and U937. The mechanism may
      correlate with the up-regulation of DR4 and DR5 of K562 and U937.

PMID- 17204178
TI  - [Ultrastructural characteristics of malignant T cell in T cell lymphoma].
AB  - In order to investigate the ultrastructural features of malignant T cell (MTC) in
      bona marrow aspirate (BMA) from patients with T Cell Lymphoma, the antigen
      expression of MTC was analyzed by flow cytometry, and the ultrastructural
      features of MTC in BMA from 13 T-cell lymphoma patients with bone marrow
      involvement (BMI) were observed by transmission electron microscopy. The results
      indicated that the sizes of MTC were uneven in every patient and their diameter
      were between 12 and 28 microm, in 6 out of 13 cases sizes of MTC were slightly
      uneven but in 7/13 cases sizes of MTC were significantly uneven. The
      heterochromatin of MTC was less than that of normal T cell and nucleolus diameter
      was from 2 to 8 microm in all cases. The nuclear contour of MTC was strikingly
      irregular in 10 out of 13 cases. The MTC had plenty of cytoplasm in 8 out of 13
      cases and displayed many microvilli or processes on MTC surface in 7 out of 13
      cases, while MTC in 6 out of 13 cases contained more Golgi's apparatuses,
      secretary vacuoles, dense granules and intermediate filaments. In 8 out of 13
      cases mitochondria apparently swelled. It is concluded that the size of MTC
      increase unevenly in all patients. MTC nuclear contour in most cases is irregular
      by folding, indenting, and twisting, which often correlated with arising of
      paranuclear intermediate filaments. Processes and microvilli on surface and
      Golgi's apparatus, secretary vesicles, dense granules as well as intermediate
      filament in cytoplasm of MTC develop synchronously, meanwhile, mitochondria of
      MTC strikingly swell in most cases.

PMID- 17204179
TI  - [Hepatosplenic gammadelta T cell lymphoma and its relationship with Epstein-Barr
      virus infection].
AB  - To explore the clinical and pathological characteristics of hepatosplenic
      gammadelta T-cell lymphoma and its relationship with Epstein-Barr virus
      infection, the clinical features of a 9-year-old girl with hepatosplenic
      gammadelta T-cell lymphoma were investigated, the smears of bone marrow was
      stained with Wright' s stain, biopsies of bone marrow and liver specimen were
      embedded in plastic and sliced about 4 microm in thickness and routinely stained
      with HE staining, the immunohistochemical staining was used to mark the tumor
      cells, and EBER probes were used to detect Epstein-Barr virus RNA. The results
      showed that the girl presented with prolonged fever, anemia, thrombocytopenia,
      hepatosplenomegaly, chronic active Epstein-Barr virus infection, and elevated
      levels of serum ferritin and lactate dehydrogenase. Bone marrow aspirate revealed
      the infiltration of atypical lymphocytes in the bone marrow stroma. The liver
      biopsy specimen revealed the infiltration of lymphocytes in the sinusoids, which
      was positive for the T-cell associated marker CD3 and activated cytotoxicity
      associated marker granzyme B. In-situ hybridization analysis with EBER probes
      revealed that the above-mentioned characteristics were negative in neoplastic
      cells. It is concluded that hepatosplenic gammadelta T-cell lymphoma is a disease
      with distinctive clinical, histopathologic, and phenotypic characteristics.
      Hepatic and/or splenic and/or bone marrow biopsy with combined phenotype is
      beneficial to diagnosis. Epstein-Barr virus infection is late event involving an
      already transformed gammadelta T-cell clone.

PMID- 17204180
TI  - [Biological properties of mesenchymal stem cells derived from bone marrow of
      patients with multiple myeloma].
AB  - The study was purposed to explore the role of mesenchymal stem cells (MSCs) in
      the pathogenesis of bone disease particularly observed in multiple myeloma (MM),
      the biological features of marrow derived MSCs from patients with MM have been
      investigated. Marrow aspirates were harvested from 11 newly diagnosed patients
      with MM and 5 normal adults and MSCs were isolated and culture-expanded by the
      cell properties of adherence to plastic flasks, The phenotype was analyzed by
      flow cytometric technique. The proliferation of MSCs was observed by MTT assay
      and their differentiation capacities into osteoblasts and adipoblasts were
      assessed with lineage-specific histochemical staining. The concentrations of IL-6
      and SCF in the culture supernatant were detected by enzyme-linked immunosorbent
      assay (ELISA). MSC culture supernatants were collected and MTT assay was
      performed to evaluate their support on the proliferation of an MM cell line
      SKO007 cells. The results showed that bone marrow-derived MSCs from MM patients
      were homogeneously positive for CD29, CD73, CD166 and HLA-ABC and negative for
      hematopoietic cell marker CD45 and endothelial cell marker CD31, the phenotype of
      which was similar to that of marrow counterparts from normal adults. MTT assay
      indicated that MSCs from MM patients or normal adults proliferated at similar
      rates. MSCs from MM patients occupied in vitro osteogenic and adipogenic capacity
      as those from normal adults. The levels of IL-6 and SCF in culture supernatant
      were greatly up-regulated in MM patients by ELISA assay. Furthermore, MSC culture
      supernatants from MM bone marrow displayed enhanced activity to promote the
      proliferation of SKO007 cells. It is concluded that marrow-derived MSCs from bone
      marrow of MM patients are normal in their proliferation and differentiation
      capacities, and myeloma bone disease may not be ascribed to the differentiation
      of MSCs while the elevated secretion of IL-6 and SCF may provide necessary cues
      for the survival of malignant myeloma cells.

PMID- 17204181
TI  - [Expression of pituitary tumor-transforming gene in patients with multiple
      myeloma].
AB  - To explore the expression of pituitary tumor-transforming gene (PTTG) in elderly
      patients with multiple myeloma (MM) and its relationship with MM, the expressions
      of PTTG mRNA were detected in bone marrow mononuclear cells (BMMNC) from 33
      patients with MM and 10 normal controls by using reverse transcriptase-polymerase
      chain reaction (RT-PCR). The results showed that the expression of PTTG mRNA in
      MM patients (0.3415 +/- 0.2172) was significantly higher than that in normal
      controls (0.0590 +/- 0.0233) (P < 0.05). It is concluded that the overexpression
      of oncogene PTTG may be related to genesis and progression of MM. It provided a
      new ideas to study the pathogenesis and gene therapy for MM patients.

PMID- 17204182
TI  - [Salvage therapy with proteasome inhibitor bortezomib for relapsed and refractory
      multiple myeloma].
AB  - Multiple myeloma is a malignant disease with high incidence in middle-aged and
      old-aged population. Bortezomib is a proteasome inhibitor which target mainly is
      NF-kappaB. This observation is to study the clinical treatment effect of
      bortezomib in one relapsed multiple myeloma (MM) patient and one primary
      refractory MM patient. The first patient diagnosed as IgA IIIA stage, whose state
      of disease became worse after 8 months of autologous peripheral blood stem cell
      transplantation. And the disease became further aggressive with 4 courses of
      chemical therapy regimen including methylprednisolone, Arsenic trioxide,
      dexamethasone, cyclophosphamide, mitoxantrone, VM-26. Myeloma cells in bone
      marrow and abnormal monoclonal immunoglobulin in blood plasma both increased.
      Bone destruction became severe, and there was a plasmacytoma about 5 x 6 cm on
      the patient's right upper chest wall. Therefore, the patient received therapy of
      bortezomib combined with doxrubicin, dexamethasone and thalidomide (VADT). After
      one course of therapy with this VADT regimen, IgA in blood plasma decreased from
      54 g/L to 6.6 g/L, and abnormal plasma cells in bone marrow decreased from 40% to
      0.6%, and plasmacytoma on the patient's right upper chest wall almost absorbed.
      But there was no obvious clinical effect after the second course of therapy of
      VADT, and the disease status became progressive again. The second patient was MM
      patient with a light chain kappa type, III B stage. There was no any effect after
      two courses of VAD therapy and one course of MOFP therapy. The patient acquired
      near complete remission after one course of treatment with VADT. Quantity of
      kappa protein in urine reduced from 24 - 30 g/24 hours to 1.12 g/24 hours. Blood
      creatinine reduced from 475.3 micromol/L to 124.2 micromol/L. Beta2-MG reduced
      from 161g/L to 64 g/L. And this patient got complete remission after three
      consecutive VADT therapy. The mainly side effects of the bortezomib regimen in
      the first patient include markedly lassitude, diarrhea, numbness of the end of
      extremities, marked increase of LDH. All the side effects could be tolerated and
      became disappeared after contraposing treatment and stopping the bortezomib
      regimen therapy. The second patient complicated with severe subacute left
      hemiplegia after the bortezomib dose had been increased to 1.45 mg/m2 at the
      third time of the first VADT course and the complication became worst at the
      following day. The upper limb muscle strength was only 1 grade and the lower limb
      muscle strength was 2 grade. Then the condition improved with the support therapy
      and gradually recovered after two weeks. Therefore, bortezomib is an effective
      target drug for therapy in refractory multiple myeloma, and more attentions to
      the side effects should be paid in order to deal with those side effects in time.

PMID- 17204183
TI  - [Construction and expression of a prokaryotic expression plasmid of idiotypic
      vaccine against B cell lymphoma: encoding the fusion genes of single-chain
      variable fragment and MCP-3].
AB  - The aim was to construct a prokaryotic expression plasmid encoding the fusion
      gene of single-chain variable fragment and monocyte chemotactic protein-3 (MCP
      3). The cDNAs of immunoglobulin (Ig) VH and Ig VL were amplified by RT-PCR and
      assembled into the single-chain variable fragment (scFv) by recombinant PCR
      method. The cDNAs of Ig VH and Ig VL were connected by a (Gly4Ser)3 linker. Then,
      the fragments of scFv and MCP-3 were connected with a NDAQAPKS spacer, using
      recombinant PCR method again. The results indicated that the fusion gene of scFv
      MCP-3 were constructed correctly and cloned into the prokaryotic expression
      plasmid successfully identified by sequencing and restriction endonucleases
      examination. Finally, the fusion protein was expressed in E coli DH5alpha under
      induction by arabinose. And the fusion protein was 65 kD and account for 30% of
      the total protein of the bacteria. In conclusion, a prokaryotic plasmid, encoding
      the fusion gene of single-chain variable fragment with MCP-3 and expressing
      idiotype protein vaccination against B cell lymphoma, was constructed correctly.

PMID- 17204184
TI  - [Characteristics of T cell receptors recognizing antiphospholipid syndrome
      associated antigens].
AB  - To understand the characteristics of T cell receptors recognizing
      antiphospholipid syndrome associated antigen, the characteristics of T cells were
      analyzed using T cell receptor beta variable region (TCRbetaV) gene spectrotyping
      in a case of antiphospholipid syndrome (APS). The results indicated that in the
      case of APS there were 2 dominant T cell clones. The TCRbetaVs sequences of the 2
      T cell clones showed the TCRbetaVs belonged to 8 and 23 gene families
      respectively. The peptides of third complementarity-determining regions (CDR3) in
      the TCRbetaVs were CASSLLVAGGPRAYNEQFFGPG and CASSLAGFGQPQHFGDG. Comparing the
      motifs in CDR3 with another autoimmune disease, the motif YNEQFFGPG in TCRbetaV8
      and motif QHFGDG in TCRbetaV23 were identical with that of idiopathic
      thrombocytopenic purpura and systemic lupus erythematosus reported before. In
      conclusion, some T cell clones proliferating in these autoimmune diseases may
      recognize the same antigens.

PMID- 17204185
TI  - [Construction of fusion gene between IgGHV and IL-2 as IgHV nucleic acid vaccine
      against lymphoma].
AB  - The purpose of this study was to construct the IgHV and IL-2 coexpressed vector.
      The IgHV gene fragments were obtained from the peripheral blood of patients with
      lymphoma, and were cloned into eukaryotic expression vector. Meanwhile, the gene
      fragments of IgHV linked with gene of IL-2 were inserted into pcDNA3.0 to form a
      fusion gene of IgHV-IL-2. Then fusion genes were transfected into COS cells by
      Lipofectin and the expression of IL-2 was detected by ELISA. The results showed
      that the IgHV/pcDNA3.0 expression vector was successfully constructed. The 3' end
      of IgHV was linked to IL-2 gene, and IL-2 could be correctly expressed. In
      conclusion, the expression vector of IgHV-IL-2 can express IL-2 correctly in COS
      cells.

PMID- 17204186
TI  - [Comparison of expanding dendritic cells derived from cord blood and mobilized
      peripheral blood by two-step culture method].
AB  - To compare the expansion efficiency and function of dendritic cells derived from
      CB-CD34+ cells and MPB-CD34+ cells by using two-step culture method, enriched CB
      CD34+ cells or MPB-CD34+ cells with immunoadsorption were primarily cultured in
      the presence of FL, SCF, TPO, GM-CSF for 10 days, and then further cultured with
      a combination of GM-CSF, IL-4, TNF-alpha, CD40Ab and PGE2 to induce DC. The DC
      phenotypes were detected by flow cytometry, the expansion efficiency and cell
      function were evaluated by mix-lymphocyte reaction (MLR), IL-12 level was
      detected by using ELISA and the chemotactic function mediated by secondary
      lymphoid tissue chemokine (SLC) was determined with Transwell plate. The results
      indicated that after 10 days of expansion, there were no significant difference
      in the percentage of CD14+CD1a- cells between CB and MPB [(40.48 +/- 16.85)% vs
      (28.07 +/- 23.19)%, P > 0.05], but the expansion of total cells in CB was higher
      than that in MPB (388.88 +/- 84.63-fold vs 79.67 +/- 10.32-fold, P < 0.01), so
      the yield of CD14+CD1a- cells from CB was significantly higher than that from MPB
      too (189.42 +/- 25.02-fold vs 28.74 +/- 23.27-fold, P < 0.01). The percentage of
      CD83+ DCs cultured with CD40Ab/PGE2 derived from CB were higher than those
      cultured with TNF-alpha derived from MPB respectively [(34.52 +/- 11.22)% vs
      (3.70 +/- 2.27)% and (36.69 +/- 13.36)% vs (7.34 +/- 3.364)% respectively, P <
      0.01]. In the same circumstance, the yield of CD83+ DCs derived from CB was much
      more than that from MPB (198.72 +/- 117.53 times vs 33.95 +/- 6.19 times, P <
      0.01). There were no difference in stimulating capacity, IL-12 secretion and
      migration capacity between DCs derived from CB and MPB. It is concluded that DCs
      induced from CB-CD34+ cells by two-step culture possess similar functions with
      that from MPB-CD34+ cells, but the yield of DCs from CB CD34+ cells is much more
      than that from MPB CD34+ cells.

PMID- 17204187
TI  - [Production of specific CTL induced by exosomes derived from K562 cells].
AB  - The aim of this study was to investigate whether exosomes derived from K562 cells
      and human monocyte-derived dendritic cells (DCs) transfected with total RNA of
      K562 cells are capable of inducing antigen-specific cytotoxic T lymphocytes (CTL)
      responses in vitro. DCs were generated from peripheral blood mononuclear cells
      (PBMNC) of healthy volunteers in the presence of GM-CSF and IL-4, and then were
      transfected with K562 RNA by using DOTAP lipofection. Exosomes was extracted from
      the supernatant of DCs and K562 cells. The T cell were activated to be tumor
      specific CTL after DCs and exosomes were co-cultured with autologous T cells
      derived from healthy volunteers' PBMNC. The effect of CTL on K562 cells was
      detected by MTT assay. The results showed that treatment of T cells with exosomes
      derived from K562 cells or DCs transfected with total RNA of K562 cells could
      significantly promote their killing ability on K562 cells as compared with
      untreated T cells (P < 0.05). The killing ability of T cells treated with
      exosomes on K562 cells was stronger than on HL-60 cells (P < 0.05). It is
      concluded that the specific CTL immune response to leukemia cells can be induced
      by exosomes derived from K562 cells.

PMID- 17204188
TI  - [Positive immunoregulation of thalidomide on human peripheral blood mononuclear
      cell cultures].
AB  - This study was purposed to investigate the effects of thalidomide on
      proliferation of peripheral blood mononuclear cells (PBMNCs), levels of
      lymphocyte subsets, secretion of cytokines and its killing activity, and to
      elucidate the immunoregulation mechanisms in treatment of multiple myeloma with
      thalidomide. The method of MTT was used to detect the effects of thalidomide on
      the proliferations and the cytotoxic activity of PBMNC; the flow cytometer was
      used to analyze the lymphocyte subsets; the ELISA was used to measure the
      concentrations of cytokines in culture supernatants. The results showed that
      thalidomide enhanced the proliferations of the CD8+ T, NK cells in PHA-stimulated
      PBMNC from healthy volunteers, increased the secretion of IL-6 significantly, and
      decreased the secretion of IFN-gamma, and the secretions of IL-2 and IL-10 were
      not affected. Compared with control group, at the same ratio of effectors to
      targets the thalidomide (5 microg/ml) could enhance the cytotoxic activity of
      PBMNC (P < 0.01), the cytotoxic activity was maximal when the ratio of effectors
      to targets was 40:1. It is concluded that thalidomide preferentially enhances the
      proliferations of CD8+ T, NK cells in PHA-stimulated PBMNC from healthy
      volunteers, and enhances the cytotoxic activity of PBMNC by increasing the
      secretion of IL-6 significantly, in short, thalidomide can exert anti-myeloma
      effects by increasing cellular immune function.

PMID- 17204189
TI  - [Construction of HA-1-DC nucleic-acid vaccine and induction of specific cytotoxic
      T lymphocytes].
AB  - The purpose of this study was to construct a HA-1-DC nucleic acid vaccine and to
      induce anti-leukemia effect after hematopoietic stem cell transplantation (HSCT).
      The dendritic cells (DCs) were generated from HSCT donors in vitro, and its
      immunologic activity was studied by using flow cytometry and mix lymphocyte
      reaction. HA-1 gene was electroporated into the cultured DCs to construct a DC
      nucleic acid vaccine. After transfecting for 48 hours, the expression of HA-1
      protein was detected by Western blot. The DCs were cultured with isogenic
      lymphocytes to induce specific cytotoxic T lymphocytes (CTLs). The cytotoxicity
      of the CTLs was detected by LDH assay. The results showed that the DCs derived
      from peripheral blood monocytes (PBMCs) expressed the DC phenotype, and were
      effective in stimulating proliferation of the allogenic lymphocytes. After
      electroporating for 48 hours, HA-1 protein was detected by Western blot. The
      cytotoxity of inducing CTLs was higher than that in the control group. It is
      concluded that the minor histocompatibility antigen HA-1 can be considered as a
      target of immunotherapy against leukemia after HSCT.

PMID- 17204190
TI  - [Feasibility of HLA-DRB1 matching by using DHPLC].
AB  - To study feasibility of HLA-DRB1 matching by using denatured high performance
      liquid chromatography (DHPLC), 20 pairs of DNA samples from donors and recipients
      of hematopoietic cell transplantation (HCT) for DRB1 matching and 2 pairs of
      samples from donors and recipient of HCT for DRB1 mismatching were studied by
      DHPLC and PCR-SSP. After being amplified and annealed slowly to produce
      heteroduplex, PCR products for exon 2 of DRB1 were detected by DHPLC to find
      matched or mismatched peaks in chromatogram. The results showed that DHPLC and
      PCR-SSP were consistant with matched or mismatched HLA-DRB1 typing. The results
      of DHPLC and PCR-SSP for matching were compared by using kappa test (kappa =
      0.776, P = 0.00), which suggested DHPLC for HLA-DRB1 matching was in agreement
      with PCR-SSP. In conclusion, DHPLC for HLA-DRB1 matching is economic and
      convenient, moreover, will not be affected by unknown genes in HLA-DRB1 locus.

PMID- 17204191
TI  - [Sequence analysis of HLA-B*4061 allele newly found].
AB  - The aim of this study was aimed to investigate the molecular genetic basis for a
      novel HLA allele, HLA-B*4061, in Chinese population. DNA was extracted from whole
      blood by salting-out method. The HLA-B exons 1 - 8 of the proband was amplified
      and the amplified product was cloned using TOPO TA cloning sequencing kit to
      split the two alleles apart. Both strands of exons 2, 3 and 4 of chosen colonies
      were sequencing. The PCR-SSP was performed to confirm the mutations detected by
      sequencing. The sequencing results showed HLA-B alleles of the proband as B*4601
      and the novel allele. The sequences of the novel allele have been submitted to
      GenBank (DQ089628, DQ089629, DQ089630). After HLA blast analysis, the novel
      allele showed a single nucleotide mismatch with B*400101 in exon 2 at position
      272 C-->A, as the results, changing amino acid from Ser to Tyr at codon 67. It is
      concluded that this allele is a novel one and has been officially named B*4061 by
      the WHO Nomenclature Committee.

PMID- 17204192
TI  - Human fetal heart-derived adherent cells with characteristics similar to
      mesenchymal progenitor cells.
AB  - This study was aimed to investigate if human heart harbored a population of
      primitive undifferentiated cells with the characteristics of MPC. Cells were
      isolated from human fetal heart and were cultured under conditions appropriate
      for bone marrow-derived MPCs. Their morphology, phenotypes and functions were
      tested by methods developed for MPC from other sources. The results showed that
      morphologically, cells were spindle shaped and resembled fibroblasts. In their
      undifferentiated state, cells were CD73, CD105, CD29, CD44, HLA-ABC, CD166
      positive and CD45, CD34, CD86, HLA-DR negative. When cultured in adipogenic,
      osteogenic or chondrogenic media, cells differentiated into adipocytes,
      osteocytes and chondrocytes respectively. They could be extensively expanded in
      vitro and exhibited very low immunogenicity as evaluated by T cell proliferation
      assays. It is concluded that cells isolated from fetal heart possess similarity
      to their adult and fetal bone marrow counterparts in morphologic,
      immunophenotypic, and functional characteristics.

PMID- 17204193
TI  - [Application of nucleic acid sequence-based amplification in detection of
      cytomegalovirus mRNA of recipients after allogeneic peripheral blood stem cell
      transplantation].
AB  - The study was purposed to investigate diagnostic value of late-mRNA detection by
      nucleic acid sequence-based amplification (NASBA) technique for human
      cytomegalovirus (HCMV) infection of the recipients after allogeneic peripheral
      blood stem cell transplantation (allo-PBSCT) and to evaluate the clinical
      significance for guiding antiviral therapy. 352 samples were collected from 128
      transplant patients after allo-PBSCT. A molecular biological diagnostic technique
      -NASBA was used to detect human cytomegalovirus (HCMV) late mRNA encoding the
      viral structural protein PP67 (UL65) expression in peripheral blood of recipients
      after allo-PBSCT, and the detected results were compared with HCMV DNA detection
      by PCR. The sensitivity, specificity and early diagnostic value of HCMV mRNA
      detection for HCMV disease were evaluated. The results showed that out of 352
      detected blood specimens from 84 patients 183 specimens (51.99%) were positive of
      HCMV DNA by PCR, 105 specimens (29.83%) were positive of HCMV mRNA by NASBA. 45
      patients were infected by HCMV. The sensitivity and specificity of HCMV DNA and
      HCMV mRNA for detecting HCMV disease were 95.56% (43/45), 93.33% (42/45) and
      60.24% (50/83), 97.59% (81/83). The results of specificity showed significant
      difference between two groups of HCMV mRNA and HCMV DNA (P < 0.05). It is
      concluded that the detection of late-mRNA of HCMV by NASBA technique is rapid,
      sensitive and specific detection for HCMV active infection. The detected result
      correlates with clinical symptoms. It can monitor HCMV infection of allo-PBSCT
      transplanted recipients and provide indication to antiviral therapy.

PMID- 17204194
TI  - [Increment of chemokine CXCL9/Mig in plasma correlated with acute graft-versus
      host disease after allogeneic hematopoietic stem cell transplantation].
AB  - To investigate the relationship between the plasma levels of chemokine CXCL9/Mig
      and acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem
      cell transplantation (allo-HSCT). The plasma levels of CXCL9/Mig of 35 patients
      who received all-HSCT were detected by using ELISA assay, these patients included
      13 patients with grade 0-I, 12 patients with grade II and 10 patients with grade
      III - IV aGVHD, respectively. The four different time points including prior to
      allo-HSCT, one week before aGVHD onset, the plateau of aGVHD and time after
      completely controlled, were studied. The results showed that the plasma levels of
      CXCL9/Mig in the patients with serious aGVHD (grade II - IV) were significantly
      increased during aGVHD than those in the patients without aGVHD or with slight
      aGVHD (P < 0.001). It was found that CXCL9/Mig levels were significantly
      correlated with the severity of grade aGVHD (P < 0.001). Another important
      finding was that CXCL9/Mig levels obviously increased at one week before aGVHD
      was diagnosed. CXCL9/Mig level was not obviously correlated with CMV infection or
      other infectious complication (P > 0.05). It is concluded that the plasma level
      of CXC19/Mig significantly correlated with the severity of aGVHD and plays a
      critical role in pathogenesis of aGVHD, the changes in plasma level of CXCL9/Mig
      after allo-HSCT may be used as a valuable indicator for early diagnosis of aGVHD,
      finally, provide a early therapeutic approach to reduce aGVHD severity and
      improve the outcome for patients after allo-HSCT.

PMID- 17204195
TI  - [Prevalence of human herpesvirus-6 in allogeneic hematopoietic stem cell
      transplant recipients in correlation with cytomegalovirus infection].
AB  - In order to study the prevalence of human herpesvirus 6 (HHV-6) in allogeneic
      hematopoietic stem cell transplant (allo-HSCT) recipients in China and to analyze
      the relationship between HHV-6 and cytomegalovirus (CMV) infection in post-HSCT
      patients, nested polymerase chain reaction (PCR) was used to monitor HHV-6
      DNAemia in 72 consecutive allo-HSCT recipients. 680 EDTA anticoagulated
      peripheral blood specimens were gathered before HSCT or weekly until 12 weeks
      after allo-HSCT. The variants of HHV-6 were identified by Hind III restriction
      analysis. CMV-pp65 antigenemia was detected by immunofluorescence stain. The
      results showed that HHV-6 DNAemia was detected at least once in 62.5% (45/72) of
      the patients on the median day 14 (range, 7 - 63 days) after allo-HSCT, and HHV
      6B was the predominant variant. CMV antigenemia was detected at least once in
      65.3% (47/72) of the patients on the median day 43 (range, 14 - 105 days) after
      allo-HSCT. Co-infection of HHV-6 and CMV (HHV-6+/CMV+) occurred in 52.8% (38/72)
      recipients. The onset of HHV-6 DNAemia was earlier than that of CMV antigenemia
      (P < 0.0001). Patients with HHV-6 DNAemia positive were more likely to have
      concurrent CMV antigenemia than HHV-6 DNAemia negative patients (84.4% vs 33.3%,
      P = 0.0001) after allo-HSCT. Among the herpesvirus related disease, the
      relatively high incidence of hemorrhage cystitis (HC) occurred in 23.6% (17/72)
      of post-HSCT patients. 88.2% (15/17) of HC developed in HHV-6 positive patients,
      and 82.3% (14/17) occurred in CMV+/HHV-6+ patients. It is concluded that
      infection of HHV-6, co-infection of HHV-6 and CMV, commonly occurred in post-HSCT
      patients in China, HHV-6 infection closely related to CMV antigenemia.

PMID- 17204196
TI  - [Role of bone marrow-derived mesenchymal stem cells in reduction of graft-versus
      host disease by effecting CD4+CD25+ regulatory T cells in rats].
AB  - The study was purposed to investigate the effects and mechanism of bone marrow
      derived mesenchymal stem cells (MSCs) on graft-versus-host desease (GVHD) after
      allogeneic hematopoietic stem cell transplantation (allo-HSCT). The model of GVHD
      in rat had been established by allo-HSCT with donor derived T cells. The
      occurence of GVHD in recipients was observed in condition with or without donor
      derived MSC co-transplantation. Effects of MSCs on GVHD were analyzed by model
      rat survival rate and pathology. Proportions of CD4+CD25+ regulatory T cells were
      determined by using label spleen lymphocytes and thymocytes with double
      fluorescent-labeled antibodies and flow cytometry. The results showed that MSCs
      inhibited the lethal GVHD after HSC co-transplantation and increased the survival
      rate. The ratio of CD4/CD8 deceased in GVHD group in different levels, as
      compared with that in the experimental group. The proportion of CD4+CD25+
      regulatory T cells of spleen lymphocytes was 31.55 +/- 7.58% and 20.90 +/- 1.90%
      in experimental and GVHD groups, respectively. Similarly, the proportion of
      CD4+CD25+ regulatory T cells of thymocytes was 93.20 +/- 2.69% and 57.17 +/-
      6.79% in experimental and the GVHD groups, respectively. Meanwhile the proportion
      of CD4+CD25+ regulatory T cells was higher in experimental group than that in
      GVHD group. It is concluded that MSCs may prevent the lethal GVHD after allo-HSC
      co-transplantation and raise the survival rate of model rats by acting on the
      CD4+CD25+ regulatory T cells in vivo.

PMID- 17204197
TI  - [Difference between FOXP3 gene expressions in donor grafts with or without acute
      graft-versus-host disease].
AB  - The study was aimed to investigate the association of FOXP3 gene expression in
      donor grafts with acute graft-versus-host disease after HLA-identical sibling
      allogeneic hematopoietic stem cell transplantation. Twenty-six donor grafts
      (peripheral blood or bone marrow) and their respective clinical characteristics
      were evaluated. Flow cytometry analysis was performed to assess the percentage of
      CD4+CD25+ and CD4+CD25(high) T cells in cord blood, healthy controls' peripheral
      blood and donor grafts. Relative transcripts of FOXP3 mRNA were determined by
      real-time quantitative reverse transcription -polymerase chain reaction with
      beta2-MG as the internal control gene. The specificity of FOXP3 and beta2-MG
      amplifications was confirmed by analyzing the dissociation curves and
      electrophoresis of the target amplicon. The results showed that the CD4+CD25+ T
      cells in peripheral blood, peripheral blood stem cell (PBSC) or BM grafts
      exhibited a continuous and primarily low expression of CD25 and the frequencies
      of CD4+CD25+ T and CD4+CD25(high) T in CD4+ T cells were (48.5 +/- 16.3)% and
      (9.6 +/- 2.5)%, (42.1 +/- 14.7)% and (13.1 +/- 4.2)%, (43.4 +/- 9.6)% and (14.6
      +/- 4.5)%, respectively. There was no significant difference in the frequencies
      and absolute numbers of CD4+CD25(high) T cells between patients with aGVHD and
      patients without aGVHD (P > 0.05). The plot of log transfused cDNA amount versus
      DeltaCt had a slope of 0.0826 which indicated approximately equal efficiency of
      FOXP3 and beta2-MG amplifications in real-time PCR. The specificities of
      amplification were confirmed by analyzing the dissociation curves and
      electrophoresis of PCR products with the values of Tm 86.5 degrees C and 82.3
      degrees C, respectively. The relative transcripts of FOXP3 in PBSC grafts of
      recipients without aGVHD were 318%high as those with aGVHD (median of 41.0 x 10(
      5) and 12.9 x 10(-5), respectively) (P = 0.03). No significant difference was
      found in other related variables for GVHD. It is concluded that coexpression of
      CD4 and CD25 may be insufficient to identify regulatory T cells; FOXP3 mRNA
      expression may be specifically quantified with real-time quantitative RT-PCR
      using SYBR Green I chemistry. FOXP3 mRNA expression in donor grafts is
      significantly low in patients with aGVHD compared with patients without aGVHD. It
      indicated that the expression level of FOXP3 mRNA may be one of the useful
      indicators for in predicting aGVHD.

PMID- 17204198
TI  - [Clinical characteristics and immunophenotype of aged patients with acute
      leukemia].
AB  - In order to analyze the clinical characteristics and biological features of acute
      leukemia in elderly, 104 acute leukemia patients in elderly were retrospectively
      analyzed and compared with 71 acute leukemia patients below 60 years old. The
      results showed that: (1) the proportion of AML in the aged group (73%) was higher
      than that in the young group (54.9%), and the difference was statistically
      significant (P < 0.05), but AML (M3) was absent in the aged group; (2) the median
      of bone marrow blast cell in the aged group was significantly lower than that in
      the young group (P < 0.05); (3) in AML, the frequently of CD14 expression was
      higher in the aged group (18.8%) than that in the young group (2.6%), while the
      expression frequencies of CD15 (37.5%), CD117 (62.5%), and CD38 (59.4%) were
      respectively lower in the aged group than that in the young group which were
      (69.2%) for CD15, (89.7%) for CD17, and (84.6%) for CD38 respectively, and the
      difference was also statistically significant (P < 0.05). (4) CD19 was most
      frequently expressed in ALL of the aged group and the positive rate was 100%; (5)
      there was no significant difference in expression of special lineage antigens and
      overlapping lineage antigens between the aged group and the young group (P >
      0.05); (6) the expression frequency of unfavorable karyotypes in the aged group
      was higher than that in the young group, and the difference was statistically
      very significant (P < 0.01); (7) the complete remission rate (CR rate) in the
      aged group was 42.9%, 2-year survival rate in the aged group was 5.4%, and
      treatment-related mortality rate in the aged group was 26.8%, while the CR rate
      in the young group was 76.6%, the difference was statistically significant (P <
      0.05). It is concluded that the expression frequency of CD14 associated with
      unfavorable prognosis is higher in the aged group than that in the young group,
      while the expression frequency of CD15 associated with favorable prognosis is
      lower in the aged group than that in the young group. The expression frequency of
      unfavorable karyotypes in the aged group is higher than that in the young group.
      The CR rate of acute leukemia in elderly is low, thus the patients in elderly
      often have unfavorable prognosis.

PMID- 17204199
TI  - [PPARalpha agonist--fenofibrate inhibits LPS-induced tissue factor expression in
      THP-1 cells].
AB  - This study was aimed to investigate the influence of PPARalpha agonist on the
      expression of TF (tissue factor) in THP-1 cells. THP-1 cells were pretreated with
      different concentrations of PPARalpha agonist (fenofibrate) for definite time.
      Lipopolysaccharide (LPS)-induced TF mRNA and protein levels were detected by RT
      PCR and Western blot respectively. The results showed that fenofibrate decreased
      tissue factor protein and mRNA expression in supernatants of LPS-stimulated human
      monocytes in a concentration-dependent manner (P < 0.05 - 0.01, n = 5). It is
      concluded that fenofibrate inhibit TF expression induced by LPS in THP-1 cells,
      which may be involved in the anti-atherosclerotic effects of PPARalpha agonist.

PMID- 17204200
TI  - [Retrospective study on HIV infection among blood donors in Zhejiang Province
      over 11-year period (1993 - 2004)].
AB  - To determine HIV prevalence among blood donors in Zhejiang Province from 1993 to
      2004 years, almost 6,600, 000 blood donors information were collected and
      analyzed. Every sample was screened for markers of HIV-1 and HIV-2 by using
      commercially available ELISA kits twice, and Western blot for confirmation if
      positive or suspicious result appeared. The results indicated that during the
      study period, prevalence rate of HIV infection was 0.85/1000 donors (0.085%),
      with the rising tendency from 1:600000 in 1995 to 1:37500 in 2004. The prevalence
      of HIV infection in Zhejiang donors was significantly lower than that in donors
      of other provinces, prevalence of HIV infection in male was higher than that in
      female. In recent years, the prevalence of HIV in blood donors was obviously
      increased, but the difference among various populations began to reduce. It is
      concluded that in a low HIV prevalence area like Zhejiang province where no
      obvious AIDS occurred, risk for the expansion of the HIV epidemic was on the
      increase. Screening procedure used in transfusion services nowaday is reliable,
      but a comprehensive approach is required to make the blood more safe.

PMID- 17204201
TI  - [RHD 1227A allele frequency among Rh negative population and random population].
AB  - To investigate the frequency of RHD 1227A allele in Rh negative population and
      random population, an AS-PCR (allele specific-polymerase chain reaction) method
      was employed to detect RHD 1227A allele. RHD gene copy was determined by D
      zygosity test and RHD exon 9 nucleotide sequence analysis. The results showed
      that among 143 Rh negative donors, forty-one RHD 1227A allele carriers were
      detected, and 8 (19.51%) out of which were RhCCdee, 32 (78.05%) were RhCcdee, and
      1 (2.44%) was RhCcdEe. Thirty-five Rh negative RHD 1227A carriers had RHD gene
      deletion, and the remaining carriers were RHD 1227A homozygous. Seven (1.43%)
      individuals were detected with RHD 1227A allele among 489 random donors. They
      were all G/A heterozygous at RHD 1227 site. Serological test indicated that they
      were normal Rh positive phenotype. It is concluded that the frequency of RHD
      1227A allele is 16.43% among Rh negative population and 0.72% among the random
      population.

PMID- 17204202
TI  - [Stability of hepatitis C virus RNA in various processing and storage
      conditions].
AB  - The study was purposed to investigate whether processing and storage conditions
      might influence the stability of the HCV RNA in whole blood or in plasma. The
      samples obtained from seven patients known to be positive for HCV RNA were kept
      in different storage conditions with different anticoagulants, and at the end of
      processing the plasma samples were frozen at -80 degrees C until fluorescent
      quantitative PCR testing. The results showed that there was no significant loss
      of HCV RNA titers in whole blood anticoagulated with CPDA or ACD or EDTA or none
      (P > 0.05), while differences in comparison of the EDTA-anticoagulant storage
      condition with three other anticoagulants storage conditions at 4 degrees C after
      48 hours were significant (P < 0.05). The HCV RNA level decreased to 53.8%, 72.5%
      and 29.8% after 48 hours of storage of whole blood anticoagulated with ACD at 4
      degrees C, 25 degrees C and 37 degrees C respectively. The HCV RNA level of
      plasma samples stored at 4 degrees C and at 25 degrees C (room temperature) after
      7 days decreased to 70.9% and 25.1% respectively. After four freeze-thaw cycles
      the HCV RNA level decreased 38.9% in plasma samples. It is concluded that the HCV
      RNA is stable relatively. The HCV RNA is resistant to degradation under routine
      laboratory handling and storage conditions or blood collection, transport and
      processing conditions. The influence of different anticoagulants on the stability
      of HCV RNA is different. Blood samples would better be stored at 4 degrees C
      after collection and plasma separated within 48 hours. And it is important for
      the stability of HCV RNA undergoing asepsis blood collection process. HCV RNA
      remains stable at 4 degrees C for at least 7 days or at room temperature for 3
      days, allowing greater flexibility in samples collection and transport in
      transfusion practice nowadays. HCV RNA in plasma samples subject to up to three
      short-term freeze-thaw cycles is still stable.

PMID- 17204203
TI  - [Cold storage of rabbit platelet suspension by adding uridine diphosphate
      galactose].
AB  - This study was aimed to investigate the method to cold-store platelets with
      uridine diphosphate galactose (UDP-Gal). Rabbit heart blood was prepared for
      concentrated platelet suspension to which UDP-Gal was added, and then stored for
      ten days in 4 degrees C refrigerator. Thereafter, platelet count, mean platelet
      volume (MPV), platelet distributing width (PDW), platelet aggregation function,
      platelet activity to urge coagulation including PF3aT and APCT and apoptosis were
      determined. Meanwhile, survival time in vivo was tested after cold-stored rabbit
      platelets labeled with Cr51 were transfused into rabbits. The results showed that
      there was not significant difference for Plt count, MPV, PDW, PF3aT and APCT
      between UDP-Gal cold-stored platelet group and fresh platelet group (P > 0.05).
      On the contrary, platelet count decreased significantly, MPV, PDW jumped and
      PF3aT and APCT went down in cold control group as compared with fresh platelet
      group (P < 0.01). Apoptosis increased in UDP-Gal cold-stored platelet group as
      compared with fresh platelet group (P < 0.05), but was significantly lower than
      that in cold control group (P < 0.01). Although PagT (inducing reagent: C-PG)
      decreased, it could still be above 50% of fresh platelet. Survival time in rabbit
      in vivo was close between UDP-Gal cold-stored platelet group and fresh platelet
      group (P < 0.05). Survival rate in seventy-two hours after transfusion in the
      fresh platelet group, UDP-Gal cold-stored platelet group and cold control group
      was 57.5% +/- 7.2%, 50.3% +/- 6.3% and 0.1% +/- 0.5% respectively. It is
      concluded that the UDP-Gal can well protect cold-stored rabbit platelets and
      prolong the survival time of cold-stored platelets in vivo.

PMID- 17204204
TI  - [Signaling pathways regulating self-renewal of mouse embryonic stem cells-
      review].
AB  - Mouse embryonic stem cells (ES cells) are pluripotent in that they can give rise
      to almost all the cell types in vitro and in vivo. Also, they can sustain self
      renewal in vitro owing to symmetrical mitosis, i.e., only the cell number
      increases while the daughter cells remain pluripotent. Self-renewal and
      pluripotency of ES cells are under stringent regulation of several signaling
      pathways. Activation of either JAK-STAT3 or PI3K, the downstream cascade of
      gp130, can maintain the self-renewal of ES cells, while phosphorylation of
      another gp130-related branch, SHP2-Ras-ERK, drives the differentiation. BMP2/4
      mediated signaling is capable of suppressing the differentiation of ES cells in
      collaboration with activated JAK-STAT3 under serum free culture conditions. Other
      signaling such as Wnt also contributes to the self-renewal of ES cells.
      Generally, the network, which is composed of various signaling pathways,
      modulates the self-renewal and differentiation of mouse ES cells precisely. This
      review focuses on the role of gp130 in proliferation of mouse ES cells including
      inhibitory effect of JAK-STAT3 pathway activation on differentiation of mouse ES
      cells, maintenance effect of PI3K pathway activation on self-renewal of ES cells,
      promotive effect of SHP-2-Ras-ERK pathway activation on differentiation of ES
      cells, and influence of other signaling pathways on self-renewal of mouse ES
      cells, including maintenance effect of BMP combination with LIF under serum free
      culture conditions on self-renewal of ES cells and promotive effect of Wnt
      pathway activation on self-renewal of ES cells.

PMID- 17204205
TI  - [TGF-beta signaling during hematopoietic development--review].
AB  - Hematopoietic development is characterized by the dynamic generation of
      hematopoietic stem/progenitor cells during embryogenesis, and afterward, the
      maintaining of hematopoietic homeostasis in adult. Mouse model has been
      appreciated valuable for dissecting the regulatory mechanisms of hematopoietic
      development. As an important cytokine playing pivotal and versatile roles in the
      regulation of hematopoiesis, transforming growth factor-beta (TGF-beta) attracts
      more and more attention. In particular, gene targeting by homologous
      recombination provides a key means for systematic evaluation of how TGF-beta
      signaling is involved in hematopoiesis under physiological conditions. To further
      illustrate the functions and possible mechanisms of TGF-beta in hematopoietic
      development, hematopoietic phenotypes of targeted mutations and/or dominant
      negative transgenes of molecules within the TGF-beta signaling pathway are
      categorized and discussed in this review.

PMID- 17204206
TI  - [Immunotherapy of non-Hodgkin's lymphomas (NHL) by anti-CD22 antibody--review].
AB  - CD22 is a transmembrane sialoglycoprotein and a member of the immunoglobulin
      superfamily. Its expression is restricted to the B cell lineage and a vast
      majority of B cell NHLs. CD22 plays a key role in B cell development, survival,
      and function. Humanized anti-CD22 antibodies were developed to minimize the
      immunogenicity and to enhance effector interactions during their developments of
      diagnostic and immunotherapeutic agent. Preclinical test with anti-CD22
      antibodies indicates that a single, conjugated or radiolabeled agent has shown
      preliminary antitumor activity in patients with recurrent and heavily pretreated
      NHL. Anti-CD22 antibodies were well tolerated, without dose-dependant toxicity.
      Anti-CD22 antibodies are currently being evaluated in combination with rituximab,
      and the early results suggest that the combination of the two antibodies are well
      tolerated and may result in better clinical activity than the single agent alone.
      Thus, anti-CD22 antibodies are theoretically good candidates alone and in
      combination with other drugs in the treatment of B cell malignancies. In this
      review, the physiologic function and characteristics of CD22 antigen as target
      molecule of guide therapy for NHL, the types of anti-CD22 antibodies in therapy
      of NHL and the combination use with other antibodies were summarized.

PMID- 17204207
TI  - [Advances in the studies on human platelet alloantigen--review].
AB  - Human platelet alloantigens (HPA) are specific antigens carried by platelet
      glycoproteins, which genes showing single nucleotide polymorphism. HPA can induce
      alloantibodies bringing about alloimmune response. They play important roles in
      post-transfusion refractoriness to platelets, post-transfusion thrombocytopenic
      purpura, fetomaternal alloimmune thrombocytopenia, and graft-versus-host disease.
      Because of their side effects in clinical blood-transfusion, there were a great
      deal of studies on HPA during last few decades. This review focuses on the
      nomenclature of HPA, the polymorphisms of platelet glycoproteins, HPA typing of
      the serological and molecular technology, as well as the mechanism of
      alloimmunization to HPA and correlated diseases.

PMID- 17204208
TI  - Impaired filterability of erythrocytes from patients with chronic hepatitis C and
      effects of eicosapentaenoic acid on the filterability.
AB  - Although erythrocyte filterability plays a key role in microcirculation, it is
      unknown whether the filterability of erythrocytes from patients with chronic
      hepatitis C (CH-C) is impaired. This study aimed to investigate erythrocyte
      filterability in CH-C patients in relation to medical treatment. The mean
      erythrocyte filterability (%) for all 24 patients with CH-C (69.2 +/- 10.8%) was
      significantly lower than that for 5 normal controls (80.5 +/- 1.7%, P < 0.03). In
      8 patients, the combination therapy of ribavirin (RBV) and interferon improved
      liver function but caused anemia. The filterability after treatment (57.8 +/-
      12.8%) was lower than that before treatment (70.8 +/- 9.7%, P < 0.05). Decreased
      filterability showed no correlation with the mean corpuscular volume or mean
      corpuscular Hb concentration during treatment, suggesting that the decrease in
      filterability mainly arises from changes in erythrocyte membrane properties. We
      investigated the protective effects of eicosapentaenoic acid (EPA) on the RBV
      induced anemia. Filterability in 7 responders was markedly improved from 68.4 +/-
      4.6% to 77.4 +/- 2.4% (P < 0.001), but not in 3 nonresponders. In the responders,
      the progression of anemia was restrained. In conclusion, we found an obvious
      impairment of the filterability of erythrocytes from CH-C patients, further
      impairment of the filterability induced by oxidative membrane damage caused by
      RBV leading to hemolytic anemia, and amelioration of the filterability caused by
      the antioxidative effects of EPA.

PMID- 17204209
TI  - English for specific purposes: implications in medical education.

PMID- 17204210
TI  - Early effects of coronary artery bypass grafting on left ventricular regional
      wall motion abnormalities.
AB  - OBJECTIVE: To determine the early effects of Coronary Artery Bypass Grafting
      (CABG) on regional left ventricular wall motion abnormality in patients
      undergoing surgery for proven Coronary Artery Disease (CAD). DESIGN: Quasi
      experimental study. PLACE AND DURATION OF STUDY: Department of Cardiac Surgery,
      National Institute of Cardiovascular Diseases, Karachi. from October 2005 to
      April 2006. PATIENTS AND METHODS: A total of a 100 adult patients who underwent
      elective CABG were selected. Pre-operative echocardiography was done to note if
      segmental left ventricular wall motion at basal, mid and apical levels were
      normal, hypokinetic, akinetic, dyskinetic, or aneurysmal. Postoperative
      echocardiography was done between 4th and 6th day and change in left ventricular
      segmental wall motion was noted. RESULTS: Seventy-five patients (n=75) were
      included in the analysis. These results showed that effect of CABG on anterior
      segmental wall motion abnormalities was insignificant (p=.609), the effect on the
      anterior IVS showed deterioration of segmental wall motion and this effect was
      significant (p=.001), effect is insignificant on anteriolateral segmental wall
      motion abnormalities (p=.078), normal pre-operative segments in posterior wall
      showed stability (p=.664) while disappearance of dyskinetic, reduction in
      akinetic segments postoperatively and inferior wall motion have same effects as
      of posterior wall. Comparison of pre-operative and postoperative
      echocardiographic data revealed early improvement in segmental wall motion of
      posterior and inferior wall, while alterations in segmental wall motion of
      anterior, anterior-lateral and septal wall. CONCLUSION: Myocardial
      revascularization by CABG improves early left ventricular regional wall motion
      abnormalities where SVG is used as conduit for revascularization whereas no
      significant improvement occurs in early segmental wall motion in areas
      revascularized by LIMA.

PMID- 17204211
TI  - Systolic hypertension in adult Nigerians with hypertension.
AB  - OBJECTIVE: To determine the prevalence of both systolic and diastolic
      hypertensions in relation to age and their impacts on target organ among adult
      Nigerians with hypertension. DESIGN: Observational study. PLACE AND DURATION OF
      STUDY: The Cardiovascular Clinic of the University of Ilorin Teaching Hospital,
      Nigeria, from July 2002 to June 2003. PATIENTS AND METHODS: Newly diagnosed adult
      hypertensives, with blood pressure >or= 140/90mmHg, taken twice with mercury
      column sphygmomanometer at 3 weeks interval, were studied. The total number of
      hypertensive patients treated over this period was also taken into consideration.
      The newly diagnosed hypertensives were classified using JNC VI classification.
      The frequency of occurrence of target organ damage such as Left Ventricular
      Hypertrophy (LVH), heart failure, renal impairment etc. was charted according to
      systolic and or diastolic pressures. The occurrence of systolic or diastolic
      blood pressure was also related with the age of the patients. Blood metabolic
      parameters were compared in both systolic and diastolic blood pressures for their
      possible contributory role. RESULTS: Two thousand seven hundred and ninety-two
      adult hypertensive patients were managed over the study period. Of them, 218
      (7.8%) were newly diagnosed and studied. There were 94 males and 124 females.
      Seventy-seven (35.3%) were aged 60 years and above with equal frequency in the
      gender. One hundred and seventy-eight (81.7%) cases had combined systolic and
      diastolic pressures. Twenty-nine (13.3%) patients had systolic hypertension.
      Twenty-five (86.2%) of these 29 were aged 50 years and above and 20 (69.0%) were
      aged 60 years and above. Eleven (5.0%) patients had isolated diastolic
      hypertension and they were all in the age bracket 40-49 years. Systolic blood
      pressure was found to be rising with advancing age while diastolic blood pressure
      peaked at mid 40's and declined. Target organ damage occurred more frequently
      with systolic hypertension and advancing age than with diastolic hypertension.
      CONCLUSION: Systolic hypertension occurred more frequently in this series of
      adult Nigerians with hypertension. It was higher with advancing age and
      associated with more target organ damage than the diastolic hypertension.

PMID- 17204212
TI  - Frequency of two canals in maxillary second premolar tooth.
AB  - OBJECTIVE: To determine the frequency of two canals in relation to age and gender
      as well as role of shift cone angle radiographic technique in maxillary second
      premolar tooth. DESIGN: A cross-sectional study. PLACE AND DURATION OF STUDY: The
      study was conducted in Operative Department (Endodontic Department), Hamdard
      University Dental Hospital, Karachi, from January 2004 to February 2005. PATIENTS
      AND METHODS: One hundred and twenty patients were selected for the study, based
      on non-probability purposive sampling technique. Twenty patients were dropped out
      of the study and the data was analyzed for 100 patients. All patients were
      examined clinically as well as radiographically. Then the canals were opened to
      further confirm and treat the tooth. The findings were noted on a performa and
      then cross-tabbed for the significant difference. RESULTS: One hundred patients
      {43 males (43%) and 57 females (57%)} whose mean age was 36.2 (SD +/- 7.3} were
      treated. Forty (40) years was the age limit for dividing the patients into two
      groups. Out of 43 males, 27 (63%) were below 40 years and out of 57 females, 38
      (67%) were below 40 years. Statistical analysis with Chi-square revealed no
      significant difference. Out of 43 males, 27 (63%) had two canals and out of 57
      females, 30 (53%) had two canals with no significant difference between the two
      groups. Results of parallel X-ray were cross tabbed with shift cone angle
      technique and the difference was highly significant (Chi-square value 9.61 and p
      value 0.002). CONCLUSION: Frequency of two canals was high is not age or gender
      dependant. Shift cone angle technique should be used as radiographic support for
      the clinical examination to identify the number of canals. The second canal
      became apparent with shift cone technique in 78% cases where additional
      periapical radiographs with shift cone angle technique were taken.

PMID- 17204213
TI  - Ultrasound as a reliable guidance system for percutaneous nephrostomy.
AB  - OBJECTIVE: To determine the effectiveness and safety of ultrasound as a reliable
      guidance system for percutaneous nephrostomy (PCN). STUDY DESIGN: Quasi
      experimental. PLACE AND DURATION OF STUDY: Jinnah Postgraduate Medical Center,
      Karachi, Pakistan, from January 1997 to July 2005. PATIENTS AND METHODS: One
      hundred and fifty-three PCN were performed in 140 patients, referred from the
      Department of Urology and Transplantation, JPMC. Out of 140 patients, 137 had
      obstructive uropathy (>1 cm dilated pelvicalyceal system) of different
      etiologies. Three patients with ureteral rupture (non dilated pelvicalyceal
      system) underwent PCN for urinary diversion in the surgical ICU. The technique
      involved a pre procedural scan, initial renal puncture, placement of a guide
      wire, tract dilation and placement of 8-12 F Nephrostomy tube, entirely under
      ultrasound guidance. The machine used was 'Just vision' or 'Eccocee' with 3.5 MHz
      variable frequency convex transducer. Effectiveness in terms of successful tube
      placement and safety in terms of complications were observed. RESULTS: Out of 153
      patients there were 78 males and 62 females. The minimum age of patient was 13
      years while maximum age was 68 years, all (100%) patients had successful
      placement of PCN. Minor complications like transient gross hematuria and small
      perinephric collection occurred in 13 cases (8.5%) but was dealt with effectively
      by conservative measures. No major complications like hemorrhage, sepsis or
      periorgan damage were encountered in any of the patients. CONCLUSION: Ultrasound
      was found to be a rapid, effective, radiation-free, portable and safe imaging
      modality with minimum rate of complications that could be used as a reliable
      guidance system for critical interventions like percutaneous nephrostomies
      without using fluoroscopic units.

PMID- 17204214
TI  - Continuous infusion of small-volume fluid resuscitation in the treatment of
      combined uncontrolled hemorrhagic shock and head injury.
AB  - OBJECTIVE: To determine the effect of continuous limited fluid resuscitation on
      the hemodynamic response and survival in rats in a model of uncontrolled
      hemorrhage shock due to massive splenic injury (MSI) and head injury (HI).
      DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Dicle University
      Animal Research Laboratory, Turkey, between January and February 2005. SUBJECTS
      AND METHODS: Seventy Sprague-Dawley rats were used in this study. Group 1 rats
      (n=10) was sham-operated. In group 2 (n=10), only Massive Splenic Injury (MSI)
      was performed and untreated. In group 3 (n=10), only head injury (HI) was
      performed and untreated. In group 4 (n=10), HI and MSI were performed and were
      untreated. In group 5 (n=10), HI and MSI were performed and 15 minutes later
      treated with 7.5% NaCl. In group 6 (n=10), HI and MSI were performed, and rats
      were treated with Ringer's Lactate (RL) solution. In group 7 (n=10), HI and MSI
      were performed, rats were treated with 0.9 % NaCl. In groups 2,4,5,6 and 7
      midline incision was reopened and splenectomy was performed at 45 minutes.
      RESULTS: In group 4 rats, Mean Arterial Pressure (MAP) was decreased from 104 +/-
      6.1 mmHg to 75 +/- 19.5 mmHg at 15 minutes; heart rate decreased from 357 +/-
      24.9 beats/min to 321 +/- 62.1 beats/min and hematocrit decreased from 46 +/- 1.3
      % to 43 +/- 2.5 % (p<0.01). Similar early changes in MAP, heart rate and
      hematocrit were observed in groups 5, 6, and 7, at 15 minutes. At 45,60 and 120
      minutes, in fluid resuscitated rats (group 5,6,7) MAP, heart rate and hematocrit
      values were measured higher than group 2 and 4 (p<0.01 for all). At 120 min. in
      group 6, hematocrit was higher than group 4, 5 and 7, in group 6, total blood
      loss after splenectomy was calculated at 20 +/- 2.4% of blood volume and was the
      best value compared to other fluid resuscitated group 5 and 7 (28% and 27% of
      blood volume) (p<0.01). Mortality was lower in all fluid resuscitated groups when
      compared to group 3 and 4 (p<0.05). The median survival time was again higher in
      fluid resuscitated groups. CONCLUSION: Continuous infusion of 7.5% NaCl, RL and
      0.9 % NaCl following uncontrolled hemorrhagic shock with massive splenic injury
      and combined head injury resulted in better survival and RL did not increase
      abdominal bleeding before splenectomy was performed.

PMID- 17204215
TI  - Presentation and management of allergic fungal sinusitis.
AB  - OBJECTIVE: To assess the presentation of allergic fungal sinusitis and describe
      the line of management in our setup. DESIGN: Descriptive study. PLACE AND
      DURATION OF STUDY: Study was conducted in Otorhinolaryngology Department, Dow
      Medical College and Civil Hospital, Karachi, from January 2004 to January 2005.
      PATIENTS AND METHODS: Culture and sensitivity / fungal stain proven 20 cases of
      allergic fungal sinusitis were selected for the study, irrespective of age and
      gender. Data including age, gender, socioeconomic status, signs, symptoms,
      laboratory findings (especially Immunoglobulin E and eosinophil count) and
      imaging studies (Computed Tomography and /or Magnetic Resonance Imaging) were
      noted for the study. Pre and postoperative medical treatment, surgery performed,
      follow-up; residual/recurrence disease and revised surgery performed were also
      recorded. RESULTS: In this series, allergic fungal sinusitis was a disease of
      younger age group with an average age of 20.75 years with male dominance (70%).
      Poor socioeconomic status (80%), allergic rhinitis (100%) and nasal polyposis
      (100%) were important associated factors. Nasal obstruction (100%), nasal
      discharge (90%), postnasal drip (90%) and unilateral nasal and paranasal sinuses
      involvement (60%) were the commonest presenting features. Aspergillus (60%) was
      the most common etiological agent. In all cases (100%), increased eosinophil
      count and IgE levels were present. Orbital (20%) and intracranial (10%)
      involvement were also seen. Surgical management was preferred in all cases.
      Functional endoscopic sinus surgery in 90% cases and lateral rhinotomy in 10%
      cases were performed. Recurrence / residual disease was seen in 20% cases.
      CONCLUSION: In this series, allergic fungal sinusitis was seen in
      immunocompetent, young males, belonging to poor socioeconomic status, suffering
      from allergic rhinitis and nasal polyposis, presenting with nasal obstruction,
      nasal discharge and postnasal drip. Functional endoscopic sinus surgery was the
      most important problem solving procedure while lateral rhinotomy was reserved for
      extensive disease.

PMID- 17204216
TI  - Management of vesicovaginal fistulae in urological context.
AB  - OBJECTIVE: To find out the commonest cause of vesicovaginal fistula (VVF) and
      describe the surgical management. DESIGN: A descriptive study. PLACE AND DURATION
      OF STUDY: The Department of Urology and Transplantation, Pakistan Institute of
      Medical Sciences (P.I.M.S.) Islamabad, from January 1995 to April 2002. PATIENTS
      AND METHODS: The subjects were presenting with vesicovaginal fistulae.
      Symptomatology and demographic causes were noted. Investigation included IVU,
      cystoscopy, vaginoscopy and examination under anesthesia. Repair and outcome was
      noted. Patients presented with genitourinary fistulae other than VVF were
      excluded from the study. RESULTS: Most of the patients were young women of
      childbearing age. The causative factor of VVF in 27 (84.3%) out of 32(100%)
      patients was obstetrical trauma. Surgical repair proved to be successful through
      transabdominal route in all 24 (100%) cases of VVF and in 4 (80%) out of 5 (100%)
      cases through transvaginal route. Repair failed in the 2(100%) attempted through
      abdominovaginal route and 1(100%) through endoscopic fulguration. To describe an
      overall result, 28 (87.5%) vesicovaginal fistulae were successfully repaired at
      first attempt. CONCLUSION: Obstetrical trauma was the commonest cause of VVF in
      this series. Transabdominal repair was the most successful method of repair in
      this series. Despite the good results of surgical repair, attempt should be
      focused on the prevention of VVF.

PMID- 17204217
TI  - Metabolic syndrome: frequency and gender differences at an out - patient clinic.
AB  - OBJECTIVE: To determine the frequency of metabolic syndrome among patients
      attending an out-patient clinic of a teaching hospital and to compare the
      clinical features regarding metabolic syndrome among males and females. STUDY
      DESIGN: Cross-sectional study. PLACE AND DURATION: Aga Khan University Hospital
      (AKUH), Executive and Family Medicine Clinics, from December 2004 to April 2005.
      PATIENTS AND METHODS: All adults, above 25 years, attending the clinics for an
      executive check-up and giving informed consent were included in the study. Data
      was collected through a structured questionnaire administered to those eligible
      to participate. Metabolic syndrome was defined according to ATP-III guidelines.
      RESULTS: There were 250 participants in this study. Mean age of study
      participants was 48.94 (SD10.62) years, while approximately two-thirds, 157
      (62.8%), were male. Metabolic syndrome (those who had 3 or more risk factors) was
      present in 35.2% of adults. Fasting blood sugar level was raised in 36.4% of
      study participants while significant number of participants (78.8%) had a body
      mass index (BMI) >or= 25 (p = 0.02). CONCLUSION: Frequency of metabolic syndrome
      was significantly high in this study with preponderance of males and prevalence
      similar to that observed in developed countries. Majority of patients had obesity
      and high fasting blood sugar levels. Males demonstrated higher levels of
      triglycerides and low levels of high-density lipoprotein (HDL) compared to
      females while blood pressure reading was observed to be the same in both males
      and females.

PMID- 17204218
TI  - Primary gastric lymphoma.
AB  - OBJECTIVE: To evaluate the clinico-pathological status of Primary Gastric
      Lymphoma (PGL) at presentation in King Fahad Hospital, Madina Munawra, Kingdom of
      Saudi Arabia (KSA). STUDY DESIGN: A case series. PLACE AND DURATION OF SUDY:
      Oncology Department of King Fahad Hospital, Madina Munawra, KSA, from 1990 to
      1998. PATIENTS AND METHODS: Case records of 22 patients with a histologically
      confirmed diagnosis of PGL were analyzed. Tumors were staged according to the Ann
      Arbor Classification and divided according to the Rappaport working formulation.
      According to the treatment modality, different groups were established. Any other
      histopathological type was excluded from the study. Data were analyzed by
      frequency calculations. Survival was calculated from the date of surgery.
      RESULTS: All cases were Non-Hodgkin Lymphoma (NHL). The peak age was in the sixth
      decades with a slight male preponderance. Most common presenting symptoms were
      epigastric or upper abdominal pain with or without mass. There were 10 (45%)
      patients with stage II, and 6 (27%) patients each with stage III and IV diseases.
      Diffuse large cell lymphoma was found in 12 (55%), poorly differentiated lymphoma
      in 3 (14%) and diffuse mixed in 7 (32%). Helicobacter pylori infection was found
      in 2 (9%). Sixteen (73%) patients underwent chemotherapy with some surgical
      resection, in 5 (23%) surgical procedure was palliative bypass and 11 (50%) had
      partial gastrectomy. Three (14%) had only chemotherapy after endoscopic biopsy.
      Two (9%) patients needed urgent surgical intervention. One (5%) patient had total
      gastrectomy followed by radiotherapy. Eleven (50%) had more than 3 years
      survival. CONCLUSION: PGL is usually of NHL type, presenting in the sixth decade,
      and can be successfully treated with both surgery and chemotherapy when patients
      presented at stage II. Chemotherapy after sub-total gastrectomy or biopsy was the
      best treatment option.

PMID- 17204219
TI  - Late probing for congenital nasolacrimal duct obstruction.
AB  - OBJECTIVE: To determine the outcome of late Nasolacrimal Duct (NLD) probing in
      children 2 years and above and to identify the cause of failure in these
      children. STUDY DESIGN: Quasi- experimental. PLACE AND DURATION OF STUDY: Shri
      Ganapati Netralaya, Jalna, India, from January 1999 to June 2003. PATIENTS AND
      METHODS: Clinical diagnosis of Congenital Nasolacrimal Duct Obstruction (CNLDO)
      was defined in a child who presented with history of tearing and/or eye
      discharge. Probing was performed under general anesthesia. Intraoperative patency
      of probing was determined when fluorescein stained saline was recovered from
      throat after syringing. The type of obstruction was noted in each case as simple
      obstruction where the probe could bypass the obstruction and post-probing
      syringing was patent in these cases, and complex where the probe was snugly fit
      and/or could not pass the obstruction and syringing was not patent in these
      patients. Success was the main outcome measure and was defined as complete
      resolution of tearing and discharges in the affected eye. RESULTS: Forty-nine
      eyes of 42 children were included in the study. The age range was from 2-7 years
      (average age 3.7 years). Probing was successful in 39 eyes (79.60%). Success rate
      was 85% in children less than 5 years and 55.55% in those older than 5 years. Out
      of the failed 10 cases, 5 (50%) were above 5 years of age. All cases with failed
      probing had complex type obstruction. CONCLUSION: Probing is a viable option in
      older children. The success rate for probing depends upon the type of obstruction
      and children with complex obstruction are at high risk for failure of probing.

PMID- 17204220
TI  - Chemical versus surgical sphincterotomy for chronic fissure in ano.
AB  - OBJECTIVE: To evaluate the efficacy and costs of chemical (topical glyceryl
      trinitrate ointment) versus lateral internal sphincterotomy for the treatment of
      chronic anal fissure. DESIGN: A quasi-experimental study. PLACE AND DURATION OF
      STUDY: This study was conducted at D.H.Q. /Allied Hospital, Faisalabad from
      November 2001 to October 2003. PATIENTS AND METHODS: Out of 74 patients, topical
      treatment was applied to 46. Eighteen patients never followed this modality of
      treatment so were excluded from the study. The remaining 28 patients applied 0.2%
      glyceryl trinitrate ointment on their anal verge thrice-a-day for two months. The
      patients in urgency due to pain or refused topical modality were treated by
      surgical sphincterotomy. Twenty-eight patients were allocated to undergo surgical
      sphincterotomy. The patients were followed-up and the extent of improvement in
      presenting symptoms, side effects, complications and costs of these modalities
      were noted on the questionnaires. RESULTS: Chemical sphincterotomy relieved
      symptoms only in 18 (64.3%) patients while surgical sphincterotomy relieved 28
      (100%) patients. In the former, recurrence occurred in 6 (33.3%) patients, but in
      the later group incontinence of flatus/ faeces was present in 18 (64.3%) at first
      week which resolved by eighth weeks. Wound related complications in 4 (14.2%)
      cases were noted. Average costs of treatments excluding hospital expenditures
      were Rs. 164 and Rs. 1244 respectively. CONCLUSION: Topical modality proved to be
      cost-effective and non-invasive than the surgical modality, but later was
      superior regarding healing of anal fissures.

PMID- 17204221
TI  - Frequency of infection in cholelithiasis.
AB  - OBJECTIVE: To determine the frequency of infection in cholelithiasis and find
      common infecting organisms with their antibiotic sensitivity. DESIGN: A
      descriptive study. PLACE AND DURATION: This study was conducted in Surgical Unit 
      I, Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan, from April 2001
      to March 2002. PATIENTS AND METHODS: First 100 cases of cholelithiasis, selected
      and operated by open or laparoscopic cholecystectomy were included in this study.
      Patients with acute cholecystitis, history of jaundice, stones and / or dilated
      common bile duct were excluded from the study. Ultrasound was the main tool for
      pre-operative diagnosis. During cholecystectomy, bile was aspirated and specimens
      were sent to laboratory for microbiological examination. The results were
      recorded on a proforma. RESULTS: Out of 100, 36 patients had positive bile
      culture. The most common organism was E. coli (17 patients) followed by
      Klebsiella (9), Pseudomonas (6), Staphylococcus aureus (2), Salmonella (1) and
      Bacteroids fragalis (1) patient. In this study, most of the biliary organisms
      were highly sensitive to the 2nd generation cephalosporins and quinolones.
      CONCLUSION: From the bacteriological assessment, it seems that both endogenous
      and exogenous contamination were the causes of wound sepsis. It was also found
      that the infection of bile did not increase the risk of postoperative wound
      infection when prophylactic perioperative antibiotics were used.

PMID- 17204222
TI  - A rare cause of intermittent dysphagia: giant fibrovascular polyp of the proximal
      esophagus.
AB  - Fibrovascular polyps account for only 0.5-1% of all benign esophageal tumors and
      causes intermittent dysphagia. The patient was a 63-year-old gentleman with
      gradually progressive intermittent dysphagia of 40 days duration. Investigations
      revealed a submucosal tumor of the proximal esophagus causing luminal compromise.
      Excision was performed through a cervical esophagotomy and specimen was subject
      to histopathological examination. Postoperative recovery was uneventful and he
      was completely relieved of his symptoms.

PMID- 17204223
TI  - Juvenile Ewing sarcoma presenting as a pelvic mass.
AB  - A teen aged girl with rapidly developing pelvic mass, associated with weight loss
      and left leg weakness, was evaluated and found to have Ewing's sarcoma of non
      osseous origin from pelvis, which is a rare situation. She was treated by a
      multidisciplinary approach by surgery, chemotherapy and rehabilitation by
      physiotherapy to effective response.

PMID- 17204224
TI  - Fenton syndrome in an adolescent.
AB  - Scapho-capitate fracture (Fenton syndrome) is a rare lesion and is even less well
      documented in adolescents. The most frequent mechanism is possible forced
      extension and hyperextension of the wrist. We report a case of 15 years old boy
      with hyperextension injury to the wrist. The true diagnosis was made 2 weeks
      later. Treatment involved open reduction and internal fixation with K-wires and
      Herbert screws. It went on to heal well and at 6 months follow-up, there was no
      infection or avascular necrosis and wrist function was good.

PMID- 17204225
TI  - Mayer Rokitansky Kuster Hauser syndrome with urogenital sinus anomaly.
AB  - Mayer Rokitansky Kuster Hauser (MRKH) syndrome is a rare disorder, characterized
      by the congenital absence of uterus and associated renal tract anomalies. The
      case presented with primary amenorrhea and primary infertility, despite
      development of normal female secondary sexual characteristics. CT scan revealed
      absent uterus, a solitary left sided pelvic kidney and a vesicovaginal
      communication that, on cystoscopy, revealed urogenital sinus anomaly manifesting
      as a common channel formed due to absent anterior wall of vagina and posterior
      wall of urethra. The urogenital sinus anomaly in MRKH syndrome has not been
      reported earlier.

PMID- 17204226
TI  - Impact of a workshop on the knowledge and attitudes of medical students regarding
      health research.

PMID- 17204227
TI  - 'Koro' in a 13 years old boy of interior Sindh - a mistreated cultural syndrome.

PMID- 17204235
TI  - Home injuries mortality: sensitivity and specificity analysis of different data
      sources and operative definitions.
AB  - The aim of this longitudinal study was to test different operational definitions
      of home accident mortality. METHODS: The sources of data were the Emergency
      Information System, hospital discharge reports and the mortality registry of the
      Lazio Region, 2000-2001. We selected all emergency room visits for unintentional
      traumas that occurred at home. A 9-month follow-up was performed to calculate
      mortality rates. A sensitivity analysis of in-hospital mortality, deaths within
      30 days and deaths from home accident E-codes was performed. A gold standard
      definition of home accident-related deaths was proposed. RESULTS: We observed 598
      home accident-related fatalities (29.1% of all the deaths found in the follow-up
      study). In-hospital mortality, deaths within 30 days and deaths for home accident
      E-codes had sensitivity values of 63.4%, 63.4% and 59.4%, respectively; positive
      predictive values were 78.1%, 67.1% and 100%, respectively. CONCLUSIONS: The best
      operational definition of home injury was based on in-hospital mortality, while
      mortality based on E-codes reported on death certificates was lacking. In order
      to measure the real burden of home injuries, hospital and mortality data must be
      integrated.

PMID- 17204236
TI  - End-point focus manipulations to determine what information is used during
      observational learning.
AB  - We required two groups of participants to observe an end-point model (ENDPT)
      while another two groups viewed a full-body, point-light model (FULL) to
      determine the role of relative motion information in acquisition of a multi-limb,
      whole-body action. One ENDPT and one FULL group also bowled a ball. Following
      retention, all groups observed the FULL model. The participants' movements were
      compared to the model and outcome attainment was quantified. There was no
      difference in shoulder-elbow coordination between groups in acquisition or
      retention. The FULL groups replicated hip-knee coordination more accurately than
      did ENDPT groups in early acquisition only, with no significant differences in
      late acquisition or retention. Both bowling groups became more accurate at the
      task across acquisition, but the ENDPT group was more accurate and consistent in
      retention. Providing intra-limb relative motion in re-acquisition did not improve
      coordination for the ENDPT groups, but it did facilitate movement control (peak
      wrist velocity) and outcome attainment (target accuracy). The acquisition of
      coordination during observational learning is not only a result of copying
      relative motion information, but also involves copying of end-point trajectory
      information from the primary effector.

PMID- 17204237
TI  - Association of vasoactive intestinal peptide with polymer-grafted liposomes:
      structural aspects for pulmonary delivery.
AB  - A polymer-grafted liposomal formulation that has the potential to be developed
      for aerosolic pulmonary delivery of vasoactive intestinal peptide (VIP), a potent
      vasodilatory neuropeptide, is described. As VIP is prone to rapid proteolytic
      degradation in the microenvironment of the lung a proper delivery system is
      required to increase the half-life and bioavailability of the peptide. Here we
      investigate structural parameters of unilamellar liposomes composed of palmitoyl
      oleoyl-phosphatidylcholine, lyso-stearyl-phosphatidylglycerol and distearyl
      phosphatidyl-ethanolamine covalently linked to polyethylene glycol 2000, and
      report on VIP-lipid interaction mechanisms. We found that the cationic VIP is
      efficiently entrapped by the negatively charged spherical liposomes and becomes
      converted to an amphipathic alpha-helix. By fluorescence spectroscopy using
      single Trp-modified VIP we could show that VIP is closely associated to the
      membrane. Our data suggest that the N-terminal random-coiled domain is embedded
      in the interfacial headgroup region of the phospholipid bilayer. By doing so,
      neither the bilayer thickness of the lipid membrane nor the mobility of the
      phospholipid acyl chains are affected as shown by small angle X-ray scattering
      and electron spin resonance spectroscopy. Finally, in an ex vivo lung arterial
      model system we found that liposomal-associated VIP is recognized by its
      receptors to induce vasodilatory effects with comparable high relaxation
      efficiency as free VIP but with a significantly retarded dilatation kinetics. In
      conclusion, we have designed and characterized a liposomal formulation that is
      qualified to entrap biologically active VIP and displays structural features to
      be considered for delivery of VIP to the lung.

PMID- 17204238
TI  - Human normal T lymphocytes and lymphoid cell lines do express alternative
      splicing variants of human telomerase reverse transcriptase (hTERT) mRNA.
AB  - Alternative splicing of telomerase reverse transcriptase (hTERT) mRNA is known to
      contribute to regulation of telomerase activity in normal and cancerous cells,
      however, previous studies indicated that normal human T and B cells exhibited
      constitutive expression of full-length hTERT mRNA without splicing variants and
      that activation of telomerase upon stimulation of the cells was due to the
      shuttling of hTERT protein from cytoplasm to nucleus [Proc. Natl. Acad. Sci. USA
      96 (1999) 5147; J. Immunol. 166 (2001) 4826]. We found that typical variants of
      hTERT mRNA were widespread in human lymphocyte-derived cell lines and normal
      stimulated T cells. In activated T cells, induction of the full-length hTERT mRNA
      was coupled with increased hTERT protein expression and telomerase activity.
      Collectively, human normal and malignant lymphocytes, like other human cells,
      express splicing variants of hTERT mRNA and require transcriptional activation of
      the hTERT gene to acquire telomerase activity.

PMID- 17204239
TI  - Photo-dissociation quantum yields of mammalian oxyhemoglobin investigated by a
      nanosecond laser technique.
AB  - The photo-dissociations of oxyhemoglobin of several mammals, such as human,
      bovine, pig, horse, and rabbit, have been studied. By means of optical pump-probe
      technique, the quantum yields for photo-dissociation of these oxyhemoglobin have
      been determined at pH 7 and 20 degrees C. A nanosecond laser at 532 nm is used as
      the pumping source, and a xenon lamp through a monochrometer provides a probe
      light at 432 nm. The experimental results show that the quantum yields of these
      mammalian oxyhemoglobin are different from each other, especially for that of
      rabbit. By analyzing the amino acid sequences and tetramer structures as well as
      the flexibility and hydrophobicity of the different hemoglobin, possible
      explanations for the differences are proposed.

PMID- 17204240
TI  - Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by
      CLOCK-BMAL1 and LRH-1.
AB  - Small heterodimer partner (SHP; NR0B2) is an orphan nuclear receptor and acts as
      a repressor for wide variety of nuclear hormone receptors. We demonstrated here
      that mouse SHP mRNA showed a circadian expression pattern in the liver. Transient
      transfection of the mSHP promoter demonstrated that CLOCK-BMAL1, core circadian
      clock components, bound to E-box (CACGTG), and stimulated the promoter activity
      by 4-fold. Liver receptor homologue-1 (LRH-1; NR5A2) stimulated the mSHP
      promoter, and CLOCK-BMAL1 synergistically enhanced the LRH-1-mediated
      transactivation. Interestingly, SHP did not affect the CLOCK-BMAL1-mediated
      promoter activity, but strongly repressed the synergistic activation of CLOCK
      BMAL1 and LRH-1. Furthermore, in vitro pull-down assays revealed the existence of
      direct protein-protein interaction between LRH-1 and CLOCK. In summary, this
      study shows that CLOCK-BMAL1, LRH-1 and SHP coordinately regulate the mSHP gene
      to generate the circadian oscillation. The cyclic expression of mSHP may affect
      daily activity of other nuclear receptors and contribute to circadian liver
      functions.

PMID- 17204241
TI  - Decrease of hepatic delta-aminolevulinate dehydratase activity in an animal model
      of fatigue.
AB  - Fatigue can be defined physiologically as inability to maintain the expected
      power output. At present, no standard of fatigue are yet available. In order to
      find biomarkers of fatigue, we investigated the level of delta-aminolevulinic
      acid (ALA), the first intermediate metabolite in the heme biosynthetic pathway,
      in the plasma and urine of an animal model of fatigue. To prepare fatigued
      animals, we kept rats for 5 days in a cage filled with water to a height of 1.5
      cm. As a result, the plasma and urinary ALA levels were increased in the fatigued
      animals as compared with those in the control animals. One day after the rats had
      been returned to their normal cages, these increased levels were restored to the
      control ones. We also examined the activity of the enzyme ALA dehydratase (ALAD),
      which is the second enzyme in the heme biosynthetic pathway, and ALAD gene
      expression during the fatigue and its recovery sessions. The ALAD activity, as
      well as its gene expression, in the liver of the fatigued animals was decreased
      as compared with those of the control animals. Both activity and gene expression
      of ALAD were recovered to their respective control levels after the rats had been
      allowed to rest in their normal cages for 1 day. Furthermore, the activity of ALA
      synthase (ALAS), the rate-limiting enzyme in the heme biosynthesis, in the liver
      was increased after the fatigue session for 5 days. Although this level of
      increase in the plasma concentration of ALA may not induce fatigue, increase in
      plasma and urinary ALA levels can be biomarkers of fatigue.

PMID- 17204242
TI  - Co-inoculation of DNA and protein vaccines induces antigen-specific T cell
      suppression.
AB  - Immunization can sometimes lead to antigen-specific immune suppression. In this
      study, we investigated this phenomenon by testing several combinations of DNA and
      protein vaccines directed against various viruses. We find that co-inoculation of
      mice with combined DNA and protein vaccines induces immune suppression if the two
      vaccines are "matched" by targeting the same antigen. Conversely, vaccine
      combinations never lead to immune suppression if they are derived from different
      viruses and, thus, mismatched antigenically. We have further identified CD4+CD25-
      T cells as the type of regulatory T cells induced by and are responsible for
      suppressing T cell activities in an antigen-specific manner in immunized animals.
      These regulatory T cells are phenotypically unique in their expression of Foxp3,
      IL-10, and IFN-gamma. Our study thus shows for the first time that co
      administration of antigen-matched DNA and protein vaccines can generate this type
      of adaptive regulatory T cells.

PMID- 17204243
TI  - Instability of miRNA and cDNAs derivatives in RNA preparations.
AB  - Micro RNAs (miRNAs) are small RNA molecules, which function as important
      regulators of gene expression. We found that RNA preparation methods commonly
      utilized for miRNA expression studies yield highly unstable miRNAs. We studied
      the stability of four miRNAs belonging to different miRNAs families. A
      significant degradation of these molecules may be observed already three days
      after RNA isolation. Moreover, the respective cDNAs are highly unstable as well.
      Our findings indicate that instability of miRNAs and their cDNAs should be
      considered when designing miRNA expression studies.

PMID- 17204244
TI  - Bone-marrow derived hematopoietic stem/progenitor cells express multiple isoforms
      of NADPH oxidase and produce constitutively reactive oxygen species.
AB  - Consolidated evidence highlights the importance of redox signalling in poising
      the balance between self-renewal and differentiation in adult stem cells. The
      present study shows that human hematopoietic stem/progenitor cells (HSCs)
      constitutively generate low levels of hydrogen peroxide whose production is
      inhibited by DPI, apocynin, catalase, and LY294002 and scarcely stimulated by
      PMA. Moreover, it is shown that HSCs express at the mRNA and protein levels the
      catalytic subunits of NOX1, NOX2, and NOX4 isoforms of the NADPH oxidase family
      along with the complete battery of the regulatory subunits p22, p40, p47, p67,
      rac1, rac2, NOXO1, and NOXA1 as well as the splicing variant NOX2s and that the
      three NOX isoforms are largely co-expressed in the same HSC. These findings are
      interpreted in terms of a positive feed-back mechanism of NOXs activation
      enabling a fine tuning of the ROS level to be possibly used in redox-mediated
      signalling for growth and differentiation of HSCs.

PMID- 17204245
TI  - Bile acid-mediated thrombospondin-1 induction in hepatocytes leads to
      transforming growth factor-beta-dependent hepatic stellate cell activation.
AB  - In cholestasis, bile acids induce hepatocyte apoptosis, while activation of
      hepatic stellate cells (HSCs) results in fibrosis. Since transforming growth
      factor-beta (TGF-beta) is a critical mediator in this process, we hypothesized
      that bile acids may participate in TGF-beta-mediated HSC activation in
      cholestasis. Bile acid treatment increased TGF-beta transcription in hepatocytes,
      while the total TGF-beta concentration in culture media rapidly decreased
      following bile acid treatment. Bile acid treatment promptly induced
      thrombospondin-1 expression in hepatocytes, which is a potent activator of latent
      TGF-beta, whereas this induction was not observed in bile acid-treated HSCs. HSCs
      co-cultured with hepatocytes showed a significantly higher level of Smad2
      phosphorylation and collagen alpha1 synthesis following bile acid treatment than
      cells cultured without hepatocytes. Moreover, this enhanced collagen synthesis
      was significantly inhibited in the presence of TGF-beta receptor inhibitor. These
      observations imply that bile acids induce thrombospondin-1 expression in
      hepatocytes, which activates latent TGF-beta leading to HSC activation.

PMID- 17204246
TI  - BMP-4 treatment of C3H10T1/2 stem cells blocks expression of MMP-3 and MMP-13.
AB  - Microarray gene expression profiling was used to identify bone morphogenetic
      protein-4 (BMP-4) responsive factors involved in late stages of adipocyte
      commitment in C3H10T1/2 cells. The analysis revealed that the matrix
      metalloproteinase-3 (MMP-3) gene decreased 100-fold after BMP-4 treatment, and
      expression of MMP-13 decreased 19.5-fold. Uncommitted C3H10T1/2 cells exhibit
      dramatic up-regulation of MMP-3 and MMP-13 genes as cells become confluent. Real
      time RT-PCR demonstrated that BMP-4 blocks expression of both transcripts.
      Likewise, a stable committed preadipocyte line derived from C3H10T1/2 cells did
      not express MMP-3 or MMP-13 at confluence, despite never receiving BMP-4. Active
      forms of both proteins were detected in media from confluent C3H10T1/2 cells but
      not in BMP-4 treated cells. Addition of BMP-4 to confluent C3H10T1/2 cells
      repressed the expression of both genes but did not induce adipocyte
      differentiation. The findings indicate that BMP-4-induced down-regulation of MMP
      3 and MMP-13 is associated with commitment, but is insufficient to induce
      adipogenesis.

PMID- 17204247
TI  - Loss of TGF-beta dependent growth control during HSC transdifferentiation.
AB  - Liver injury induces activation of hepatic stellate cells (HSCs) comprising
      expression of receptors, proliferation, and extracellular matrix synthesis
      triggered by a network of cytokines provided by damaged hepatocytes, activated
      Kupffer cells and HSCs. While 6 days after bile duct ligation in rats TGF-beta
      inhibited DNA synthesis in HSCs, it was enhanced after 14 days, indicating a
      switch from suppression to DNA synthesis stimulation during fibrogenesis. To
      delineate mechanisms modulating TGF-beta function, we analyzed crosstalk with
      signaling pathways initiated by cytokines in damaged liver. Lipopolysaccharide
      and tumor necrosis factor-alpha enhanced proliferation inhibition of TGF-beta,
      whereas interleukin-6, oncostatin M, interleukin-1alpha, and interleukin-1beta
      did not. Hepatocyte growth factor (HGF) counteracted TGF-beta dependent
      inhibition of DNA synthesis in quiescent HSCs. Since expression of c-met is
      induced during activation of HSCs and HGF is overrepresented in damaged liver,
      crosstalk of HGF and TGF-beta contributes to loss of TGF-beta dependent
      inhibition of DNA synthesis in HSCs.

PMID- 17204248
TI  - Complex formation of 70-kDa heat shock protein with acidic glycolipids and
      phospholipids.
AB  - A new property of a heat-inducible heat shock protein (Hsp) 70.1 that it forms a
      complex with acidic lipids was first demonstrated. Based on the behaviors of the
      complexes on the native PAGE, the acidic lipid/Hsp70.1 complexes are categorized
      into two groups. The first group is the sulfatide-induced large-sized complex,
      which stays on the gel top on the native PAGE. Only the N-terminal ATPase domain
      is responsible for the complex formation. The second group is the ganglioside
      induced complex, which is diffused in the resolution gel on the native PAGE. Both
      the N-terminal ATPase and the C-terminal peptide-binding domains are involved in
      the complex formation. No complex is formed by neutral glyco- and phospholipids.
      The complex formation with the acidic glyco- and phospholipids implicates the
      various functions of Hsp70 on the membrane surfaces.

PMID- 17204249
TI  - The neural circuitry underlying the executive control of auditory spatial
      attention.
AB  - Although a fronto-parietal network has consistently been implicated in the
      control of visual spatial attention, the network that guides spatial attention in
      the auditory domain is not yet clearly understood. To investigate this issue, we
      measured brain activity using functional magnetic resonance imaging while
      participants performed a cued auditory spatial attention task. We found that cued
      orienting of auditory spatial attention activated a medial-superior distributed
      fronto-parietal network. In addition, we found cue-triggered increases of
      activity in the auditory sensory cortex prior to the occurrence of an auditory
      target, suggesting that auditory attentional control operates in part by biasing
      processing in sensory cortex in favor of expected target stimuli. Finally, an
      exploratory cross-study comparison further indicated several common frontal and
      parietal regions as being involved in the control of both visual and auditory
      spatial attention. Thus, the present findings not only reveal the network of
      brain areas underlying endogenous spatial orienting in the auditory modality, but
      also suggest that the control of spatial attention in different sensory
      modalities is enabled in part by some common, supramodal neural mechanisms.

PMID- 17204251
TI  - C-fos expression in the rat brain following lithium chloride-induced illness.
AB  - The present study examined c-Fos expression in selected brain areas consequent to
      administration of lithium chloride, the typical illness-inducing agent used in
      laboratory studies of conditioned taste aversion. The results replicated previous
      findings of significant c-Fos expression in the parabrachial nucleus, the central
      nucleus of the amygdala and the basolateral amygdala. New findings indicate
      significant lithium-induced c-Fos in the gustatory region of the thalamus and the
      bed nucleus of the stria terminalis but not in the insular cortex. The results
      are discussed with respect to the neural substrates of conditioned taste
      aversion.

PMID- 17204252
TI  - Caspase-dependent programmed cell death pathways are not activated in generalized
      seizure-induced neuronal death.
AB  - Activation of the caspase-dependent cell death pathways has been shown in focal
      seizures, but whether this occurs in prolonged generalized seizures is not known.
      We investigated whether the initiator caspase in the extrinsic pathway, caspase
      8, or the intrinsic pathway, caspase-9, is activated during the first 24 h
      following lithium-pilocarpine-induced status epilepticus, when neuronal death is
      maximal and widespread. The thymuses of rats given methamphetamine were used as
      positive controls for caspase-3-activated cellular apoptosis. Following
      methamphetamine treatment, caspase-9 but not caspase-8 was activated in
      thymocytes. However, 6 or 24 h following status epilepticus, none of 26 brain
      regions studied showed either caspase-8 or -9 activation by immunohistochemistry,
      western blotting and enzyme activity assays. Our results provide evidence against
      the activation of the extrinsic and intrinsic caspase pathways in generalized
      seizures, which produce morphologically necrotic neurons with internucleosomal
      DNA cleavage (DNA laddering), a programmed process. In contrast, there is
      increasing evidence that caspase-independent programmed mechanisms play a
      prominent role in seizure-induced neuronal death.

PMID- 17204250
TI  - Secretory phospholipase A2 IIA is up-regulated by TNF-alpha and IL-1alpha/beta
      after transient focal cerebral ischemia in rat.
AB  - Cerebral ischemia initiates an inflammatory response in the brain that is
      associated with the induction of a variety of cytokines, including tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-1alpha/beta (IL-1alpha/beta) that
      contributes to stroke injury. Transient middle cerebral artery occlusion (tMCAO)
      in spontaneously hypertensive rat (SHR) resulted in significant increases in TNF
      alpha and IL-1beta levels. We have previously demonstrated up-regulation of
      secretory phospholipase A2 IIA (sPLA2 IIA) mRNA and protein expression, increased
      PLA2 activity, and loss of phosphatidylcholine after 1-h tMCAO and 24-h
      reperfusion in SHR. Treatment with TNF-alpha antibody or IL-1 receptor antagonist
      significantly attenuated infarction volume, sPLA2 IIA protein expression, PLA2
      activity and significantly restored phosphatidylcholine levels after tMCAO. This
      suggests that cytokine induction up-regulates sPLA2 IIA protein expression,
      resulting in altered lipid metabolism that contributes to stroke injury.

PMID- 17204253
TI  - Serum S100B indicates brain edema formation and predicts long-term neurological
      outcomes in rat transient middle cerebral artery occlusion model.
AB  - To assess the usefulness of serum S100B as a biomarker, the present study
      proceeded by observing serum S100B kinetics in a rat transient middle cerebral
      artery occlusion (MCAO) model, then assessed the correlation between serum S100B
      and both brain edema formation and neurological outcomes. Study results showed
      increases in serum S100B concentrations, peaking 48 h after MCAO. Brain water
      content in the ipsilateral hemisphere significantly increased from 24 h after
      MCAO, and reached peak value 72 h after MCAO. A single measurement of serum S100B
      48 h after MCAO showed significant correlations with maximal extent of brain
      edema 72 h after MCAO. Furthermore, S100B concentrations 48 h after MCAO
      significantly correlated with infarct volumes. Neurological outcomes were
      estimated in a long-term study, where a gradual recovery was observed up to 168 h
      after MCAO. Serum S100B 48 h after MCAO was found to show higher correlation with
      neurological score 168 h after MCAO than those 48 h after MCAO. These findings
      suggest that serum S100B is an effective biomarker in predicting both extent of
      brain edema and long-term neurological outcomes in a rat transient MCAO model.

PMID- 17204254
TI  - Genetic variance contributes to naltrexone-induced inhibition of sucrose intake
      in inbred and outbred mouse strains.
AB  - The study of genetic variance in opioid receptor antagonism of sucrose and other
      forms of sweet intake has been limited to reductions in sweet intake in mice that
      are opioid receptor-deficient or lacking either pre-pro-enkephalin or beta
      endorphin. Marked genetic variance in inbred mouse strains has been observed for
      sucrose intake across a wide array of concentrations in terms of sensitivity,
      magnitude, percentages of kilocalories consumed as sucrose and compensatory chow
      intake. The present study examined potential genetic variance in systemic
      naltrexone's dose-dependent (0.01-5 mg/kg) and time-dependent (5-120 min) ability
      to decrease sucrose (10%) intake in eleven inbred (A/J, AKR/J, BALB/cJ, CBA/J,
      C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD
      1) mouse strains. A minimum criterion sucrose intake (1 ml) under vehicle
      treatment, designed to avoid "floor effects" of antagonist treatment was not
      achieved in three (A/J, AKR/J, CBA/J) inbred mouse strains. Marked genetic
      variance in naltrexone's ability to inhibit sucrose intake was observed in the
      remaining strains with the greatest sensitivity observed in the C57BL/10J and
      C57BL/6J strains, intermediate sensitivity in BALB/cJ, C3H/HeJ, CD-1 and DBA/2J
      mice, and the least sensitivity in 129P3/J, SWR/J and SJL/J strains with a 7.5
      36.5 fold range of greater effects in the ID(50) of naltrexone-induced inhibition
      in C57BL/10J relative to the three less-sensitive strains across the time course.
      Naltrexone primarily affected the maintenance, rather than the initiation of
      intake in BALB/cJ, CD-1, C3H/HeJ, DBA/2J and SJL/J mice, but significantly
      reduced sucrose intake at higher doses across the time course in C57BL/6J,
      C57BL/10J and 129P3/J mice. Whereas SWR/J mice failed to display any significant
      reduction in sucrose intake at any time point following any of the naltrexone
      doses, naltrexone's maximal magnitude of inhibitory effects was small (35-40%) in
      129P3/J and SJL/J mice, moderate ( approximately 50%) in BALB/cJ, C3H/HeJ, CD-1
      and DBA2/J mice, and profound (70-80%) in C57BL/6J and C57BL/10J mice. Indeed,
      the latter two strains displayed significantly greater percentages of naltrexone
      induced inhibition of sucrose intake than virtually all other strains. These data
      indicate the importance of genetic variability in opioid modulation of sucrose
      intake.

PMID- 17204255
TI  - Effects of progesterone on experimental spinal cord injury.
AB  - Progesterone has been proposed to be protective to the central nervous system
      following injury. This study assessed progesterone supplementation in the setting
      of contusional spinal cord injury in male and female rats. Short-term (5 days of
      either 4 or 8 mg/kg progesterone) and long-term (14 days of either 8 or 16 mg/kg
      progesterone) therapy failed to show any significant alteration in locomotor
      functioning and injury morphometrics after 21 days. This study does not support
      progesterone as a potential therapeutic agent in spinal cord injury.

PMID- 17204256
TI  - Synthesis of N- and S-bis-protected lactosyl isothiobiurets.
AB  - Several N,S-bis(hepta-O-acetyllactosyl)-1-aryl-2-isothiobiuret compounds have
      been synthesised for the first time by the reaction of S-(hepta-O-acetyl-beta
      lactosyl)-1-arylisothiocarbamides and hepta-O-acetyl-beta-lactosyl isocyanate.
      The identities of these newly synthesised compounds were established on the basis
      of elemental analysis and IR, (1)H NMR, (13)C NMR and mass spectral studies.

PMID- 17204257
TI  - Preparation of diamino pseudodisaccharide derivatives from 1,6-anhydro-beta-D
      hexopyranoses via aziridine-ring cleavage.
AB  - Twelve positional isomers of diamino pseudodisaccharide derivatives with gluco
      gluco configuration have been prepared using aziridine-ring cleavage of epimino
      derivatives of 1,6-anhydro-beta-D-hexopyranoses of the D-allo, D-manno, and D
      galacto configuration by 2-, 3-, and 4-amino derivatives of 1,6-anhydro-beta-D
      glucopyranose. The N-substitution of the aziridine ring by a 2
      nitrobenzenesulfonyl group and ionic-liquid solvent (N-methylpyridinium tosylate)
      was used to obtain cleavage products in high yield (64-93%). The cleavage
      reactions proceeded according to the Furst-Plattner rule and only trans-diaxial
      stereoisomers were formed.

PMID- 17204258
TI  - The Ruff degradation: a review of previously proposed mechanisms with evidence
      that the reaction proceeds by a Hofer-Moest-type reaction.
AB  - The Ruff degradation reaction is critically reviewed. Based on available
      information, the Hofer-Moest decarboxylation mechanism is presented as the
      mechanism for it. Cu(III) is proposed as the active species of the copper variant
      of the Ruff degradation, which is the most efficient form of the reaction.

PMID- 17204259
TI  - DFT study of alpha- and beta-D-allopyranose at the B3LYP/6-311++G ** level of
      theory.
AB  - One hundred and two conformations of alpha- and beta-D-allopyranose, the C-3
      substituted epimer of glucopyranose, were geometry optimized using the density
      functional, B3LYP, and the basis set, 6-311++G **. Full geometry optimization was
      performed on different ring geometries and on the hydroxymethyl rotamers
      (gg/gt/tg). Analytically derived Hessians were used to calculate zero point
      energy, enthalpy, and entropy. The lowest energy and free energy conformation
      found is the alpha-tg(g-)-4C1-c conformation, which is only slightly higher in
      electronic (approximately 0.2 kcal/mol) and free energy than the lowest energy
      alpha-D-glucopyranose. The in vacuo calculations showed a small (approximately
      0.3 kcal/mol) energetic preference for the alpha- over the beta-anomer for
      allopyranose in the 4C1 conformation, whereas in the 1C4 conformation a
      considerable (approximately 1.6 kcal/mol) energetic preference for the beta- over
      the alpha-anomer for allopyranose was encountered. The results are compared to
      previous aldohexose calculations in vacuo. Boat and skew forms were found that
      remained stable upon gradient optimization although many starting boat
      conformations moved to other skew forms upon optimization. As found for glucose,
      mannose, and galactose the orientation and interaction of the hydroxyl groups
      make the most significant contributions to the conformation/energy relationship
      in vacuo. A comparison of different basis sets and density functionals is made in
      the Discussion section, confirming the appropriateness of the level of theory
      used here.

PMID- 17204260
TI  - Bilberry xyloglucan--novel building blocks containing beta-xylose within a
      complex structure.
AB  - Bilberries are known to have one of the most complex xyloglucan structures
      described in the plant kingdom until now. To characterise this structure,
      xyloglucans were enzymatically degraded and the oligosaccharides obtained were
      analysed. More than 20 different building blocks were found to make up the
      xyloglucan polymer. Bilberry xyloglucan was of XXXG-type, but some XXG-type
      oligomers were present, as well. The building blocks contain galactose-xylose (L)
      and fucose-galactose-xylose (F) side chains. In both side chains, the galactose
      units can be acetylated. In addition, beta-xylose-alpha-xylose (U) side chains
      were shown. This U chain was present in three building blocks described before
      (XUXG, XLUG and XUFG) and four novel blocks that have not been described in the
      literature previously: XUG, XUUG, XLUG and XXUG.

PMID- 17204261
TI  - Re-characterization of three conjugated linolenic acid isomers by GC-MS and NMR.
AB  - Conjugated linolenic acids (CLN) refer to a group of octadecatrienoic acids with
      three conjugated double bonds. Minor positional and geometrical differences among
      CLN isomers make their separation and identification difficult. We have used GC
      MS and NMR to study three common CLN isomers namely alpha-eleostearic acid, beta
      eleostearic acid and punicic acid, finding that some signals of olefinic carbon
      atoms in NMR spectra were mistakenly assigned in the literature. The present
      study was therefore undertaken to re-characterize the location of CC double bonds
      and assign the chemical signals of proton and carbon atoms using (1)H NMR, (13)C
      NMR, (1)H-(1)H two-dimensional correlation spectra ((1)H-(1)H COSY) and (13)C
      (1)H two-dimensional correlation spectra ((13)C-(1)H COSY). The geometrical
      structure of double bonds in these three CLN isomers was identified using
      homonuclear decoupling technique.

PMID- 17204262
TI  - Cytochemical analysis of storage materials in cultured skin fibroblasts from
      patients with I-cell disease.
AB  - BACKGROUND: In cultured fibroblasts from I-cell disease patients the transport of
      many lysosomal enzymes is defective, and affected cells contain inclusion bodies
      filled with undegraded substrates. However, the contents of these inclusion
      bodies have not been well characterized yet. We attempted to identify accumulated
      substances in cultured I-cell disease fibroblasts cytochemically. METHODS:
      Cultured fibroblasts from I-cell disease patients were double-stained with a
      monoclonal antibody to lysosome-associated membrane protein-1 (LAMP-1) and that
      to GM2 ganglioside, or a series of lectins that specifically bind to sugar
      moieties. RESULTS: The patients' cells were granularly stained with the antibody
      to GM2 ganglioside and the lectins including Maakia amurensis, Datura stramonium,
      and concanavalin A. Their localization was coincident with that of LAMP-1.
      CONCLUSIONS: GM2 ganglioside and various kinds of glycoconjugates having sialic
      acidalpha2-3galactose, galactosebeta1-4N-acetylglucosamine and mannose residues
      accumulate in enlarged lysosomes in I-cell disease fibroblasts.

PMID- 17204264
TI  - Local peripheral antinociceptive effects of 14-O-methyloxymorphone derivatives in
      inflammatory and neuropathic pain in the rat.
AB  - Antinociception achieved after peripheral administration of opioids has opened a
      new approach to the treatment of severe and chronic pain. Additionally, opioid
      analgesics with restricted access to the central nervous system could improve
      safety of opioid drugs used in clinical practice. In the present study,
      peripheral components of antinociceptive actions of 6-amino acid-substituted
      derivatives of 14-O-methyloxymorphone were investigated after local intraplantar
      (i.pl.) administration in rat models of inflammatory and neuropathic pain. Their
      antinociceptive activities were compared with those of morphine, the classical mu
      opioid receptor agonist. Intraplantar administration of morphine and the 6-amino
      acid derivatives produced dose-dependent reduction of formalin-induced flinching
      of the inflamed paw, without significant effect on the paw edema. Local i.pl.
      administration of the new derivatives in rats with neuropathic pain induced by
      sciatic nerve ligation produced antiallodynic and antihyperalgesic effects;
      however, the antinociceptive activity was lower than that observed in
      inflammatory pain. In both models, the 6-amino acid derivatives and morphine at
      doses that produced analgesia after i.pl. administration were systemically (s.c.)
      much less active indicating that the antinociceptive action is due to a local
      effect. Moreover, the local opioid antinociceptive effects were significantly
      attenuated by naloxone methiodide, a peripherally acting opioid receptor
      antagonist, demonstrating that the effect was mediated by peripheral opioid
      receptors. The present data indicate that the peripherally restricted 6-amino
      acid conjugates of 14-O-methyloxymorphone elicit antinociception after local
      administration, being more potent in inflammatory than in neuropathic pain.
      Opioid drugs with peripheral site of action can be an important target for the
      treatment of long lasting pain.

PMID- 17204263
TI  - The role of TGF-beta signaling in regulating chondrogenesis and osteogenesis
      during mandibular development.
AB  - During craniofacial development, Meckel's cartilage and the mandible bone derive
      from the first branchial arch, and their development depends upon the
      contribution of cranial neural crest (CNC) cells. We previously demonstrated that
      conditional inactivation of Tgfbr2 in the neural crest of mice
      (Tgfbr2(fl/fl);Wnt1-Cre) results in severe defects in mandibular development,
      although the specific cellular and molecular mechanisms by which TGF-beta
      signaling regulates the fate of CNC cells during mandibular development remain
      unknown. We show here that loss of Tgfbr2 does not affect the migration of CNC
      cells during mandibular development. TGF-beta signaling is specifically required
      for cell proliferation in Meckel's cartilage and the mandibular anlagen and for
      the formation of the coronoid, condyle and angular processes. TGF-beta-mediated
      connective tissue growth factor (CTGF) signaling is critical for CNC cell
      proliferation. Exogenous CTGF rescues the cell proliferation defect in Meckel's
      cartilage of Tgfbr2(fl/fl);Wnt1-Cre mutants, demonstrating the biological
      significance of this signaling cascade in chondrogenesis during mandibular
      development. Furthermore, TGF-beta signaling controls Msx1 expression to regulate
      mandibular osteogenesis as Msx1 expression is significantly reduced in
      Tgfbr2(fl/fl);Wnt1-Cre mutants. Collectively, our data suggest that there are
      differential signal cascades in response to TGF-beta to control chondrogenesis
      and osteogenesis during mandibular development.

PMID- 17204265
TI  - Enhanced G-protein coupled receptors-mediated contraction and reduced endothelium
      dependent relaxation in hypertension.
AB  - The present study was designed to demonstrate a hypothesis that some G-protein
      coupled receptors are up-regulated and a dysfunction of endothelium occurs in
      hypertension. The arteries from hypertensive patients and spontaneously
      hypertensive rats (SHR) were tested. An in vitro myograph system was used to
      obtain concentration-contraction curves mediated by endothelin ET(A), endothelin
      ET(B), 5-hydroxytryptamine 2A (5-HT2A)-receptors and alpha1-adrenoceptors in the
      arterial segments. In hypertensive patients, the maximum contractions (Emax)
      induced by endothelin ET(B), endothelin ET(A) and 5-HT receptors were
      significantly increased with elevated pEC50 values, while a significantly
      leftward shift of alpha1-adrenoceptor-mediated contraction was seen. Similar
      results were obtained in SHR. Specific antagonists for 5-HT2A receptors or alpha1
      adrenoceptors rightward shifted the concentration-contractile curves induced by 5
      HT or noradrenaline, while the Emax were not significantly altered, suggesting
      that the contractions were mediated by 5-HT2A receptors and alpha1-adrenoceptors,
      respectively. Endothelium-dependent maximum relaxation (Rmax) in the arterial
      segments induced by acetylcholine was significantly decreased in both
      hypertensive patients and SHR. In addition, nitric oxide- and endothelium-derived
      hyperpolarizing factor-mediated dilatations were decreased significantly and the
      arterial endothelial cells were in part lost in SHR. In conclusion, endothelin
      ET(B), endothelin ET(A), 5-HT2A receptor- and alpha-adrenoceptor-mediated
      contractions were increased in hypertension, while the endothelium and its
      functions were damaged.

PMID- 17204266
TI  - Effects of adrenomedullin 2 on regional hemodynamics in conscious rats.
AB  - The present study aimed to assess the effects of rat adrenomedullin 2 on systemic
      and regional hemodynamics in conscious Wistar Kyoto (WKY) rats and spontaneously
      hypertensive rats (SHRs). Intravenous infusion of rat adrenomedullin 2 (0.25-5
      micro g/kg/min) decreased blood pressure, and increased heart rate in a dose
      dependent manner in both types of rats. Rat adrenomedullin 2 (5 micro g/kg/min)
      increased heart rate and cardiac output. As a result, total peripheral resistance
      significantly decreased. In SHRs, adrenomedullin 2 significantly increased
      regional blood flow in the heart, liver, spleen, kidneys, and adrenal glands.
      Especially, effects on heart, liver, and kidneys were remarkable. Regional
      hemodynamic changes were reproduced in WKY rats, and there was no qualitative
      difference in regional responses to rat adrenomedullin 2 between SHRs and WKY
      rats. Thus, rat adrenomedullin 2 predominantly increased flow rates in organs
      that were richly blood-supplied from cardiac output. Rat adrenomedullin 2 may
      contribute to the regulation of the cardiovascular system, by acting as a local
      vasodilatory hormone as well as a circulatory hormone.

PMID- 17204267
TI  - The lactoperoxidase system links anion transport to host defense in cystic
      fibrosis.
AB  - Chronic respiratory infections in cystic fibrosis result from CFTR channel
      mutations but how these impair antibacterial defense is less clear. Airway host
      defense depends on lactoperoxidase (LPO) that requires thiocyanate (SCN-) to
      function and epithelia use CFTR to concentrate SCN- at the apical surface. To
      test whether CFTR mutations result in impaired LPO-mediated host defense, CF
      epithelial SCN- transport was measured. CF epithelia had significantly lower
      transport rates and did not accumulate SCN- in the apical compartment. The lower
      CF [SCN-] did not support LPO antibacterial activity. Modeling of airway LPO
      activity suggested that reduced transport impairs LPO-mediated defense and cannot
      be compensated by LPO or H2O2 upregulation.

PMID- 17204268
TI  - The armadillo repeats of the Ufd4 ubiquitin ligase recognize ubiquitin-fusion
      proteins.
AB  - Armadillo (ARM) repeats have been identified in proteins regulating cell junction
      assembly, nuclear transport and transcription activation. Recent studies showed
      that a large number of ubiquitin (Ub) ligases (or E3s) also contain ARM repeats.
      The function of the ARM repeats in these E3s, however, remains unknown. Here we
      report that the ARM repeats of Ufd4, the E3 component of the UFD (Ub fusion
      degradation) pathway, recognize the Ub degradation signal of the UFD substrates.
      Disruption of the ARM repeats abolishes the ubiquitylating activity of Ufd4. This
      study uncovers a new role of the ARM repeats in protein ubiquitylation.

PMID- 17204269
TI  - The chronic intake of a Mediterranean diet enriched in virgin olive oil,
      decreases nuclear transcription factor kappaB activation in peripheral blood
      mononuclear cells from healthy men.
AB  - OBJECTIVE: Nuclear transcription factor kappaB (NF-kappaB) plays a key role in
      the inflammatory response and can be modulate by dietary fat. We have examined
      the effect of three diets, with different fat composition, on the activation of
      NF-kappaB on peripheral blood mononuclear cells (PBMCs). METHODS: Sixteen healthy
      men followed three 4-week diets, in a randomised crossover design: a Western
      diet, rich in saturated fat (SFA) [22% SFA, 12% monounsaturated fat (MUFA) and 0,
      4 alpha-linolenic acid]; a Mediterranean diet [<10% SFA, 24% MUFA and 0.4% alpha
      linolenic acid], and a low fat diet enriched in alpha-linolenic acid [<10% SFA,
      12% MUFA and 2% alpha-linolenic acid]. NF-kappaB (electrophoretic mobility shift
      assay) in mononuclear cells and plasma concentrations (ELISA) of soluble vascular
      cellular adhesion molecule 1 (VCAM-1) were examined after either diets. RESULTS:
      Western diet increased 2.7-fold NF-kappaB compared with the Mediterranean diet
      (p=0.038) and 1.79-fold with the alpha-linolenic acid diet (p=0.07). No
      differences were found between the last two. Furthermore, an increase on plasma
      VCAM-1 was observed with the Western diet (p<0.05). CONCLUSIONS: The
      Mediterranean diet diminished NF-kappaB activation in mononuclear cells, compared
      with Western diet, supporting its cardioprotective properties. The effect of the
      n-3 enriched diet was intermediate.

PMID- 17204270
TI  - Preparation of nitrilotriacetic acid/Co2+-linked, silica/boron-coated magnetite
      nanoparticles for purification of 6 x histidine-tagged proteins.
AB  - In this report, we describe the preparation of novel nitrilotriacetic acid/Co2+
      linked, silica/boron-coated magnetite nanoparticles for purification of 6 x His
      tagged proteins. The nanoparticles were approximately 200 nm in size and were
      stable against hydrochloric acid and had negligible non-specific binding for
      protein. Elimination of non-specific binding by nucleic acids was readily
      achieved by digestion of samples with DNase and RNase. The modified nanoparticles
      were used to purify two model proteins: one had a C-terminal 6 x His tag, and the
      other had an internal 6 x His tag. Both proteins were purified within one hour
      into single band purity on sodium dodecyl sulfate-polyacrylamide electrophoresis
      gel.

PMID- 17204271
TI  - Optimisation and validation of a solid-phase microextraction method for
      simultaneous determination of different types of pesticides in water by gas
      chromatography-mass spectrometry.
AB  - A solid-phase microextraction (SPME) method for the simultaneous determination of
      a large number of pesticides (46) with a wide range of polarities and chemical
      structures (organochlorine, organophosphorous, triazines, pyrethroids and others)
      in water samples by GC-MS has been developed. Three different fibres and
      parameters that influence the extraction and desorption efficiency were studied.
      The selected conditions were: a 60 microm polydimethylsiloxane/divinylbenzene
      (PDMS/DVB) fibre, 45 min of extraction time, sample agitation and temperature
      control at 60 degrees C; neither pH adjustment nor ionic strength correction were
      applied. Good detection limits, linearity and repeatability were obtained with
      this method for the 46 pesticides studied. The method was validated for 29
      pesticides following the recommendations of the international norm ISO/IEC 17025
      including the calculation of the uncertainties. The detection limits ranged from
      4 to 17 ng l(-1). Furthermore, repeatability (6.9-20.5%) and intermediate
      precision (4.5-19.7%) were shown to be satisfactory. To validate matrix effects
      for drinking and surface water analytical recoveries were calculated for these
      matrices. The accuracy of the method was also evaluated by participating in a
      proficiency inter-laboratory test.

PMID- 17204272
TI  - Fast and efficient separation of immunoglobulin M from immunoglobulin G using
      short monolithic columns.
AB  - Certain diagnostic, analytical and preparative applications require the
      separation of immunoglobulin G (IgG) from immunoglobulin M (IgM). In the present
      work, different ion-exchange methacrylate monoliths were tested for the
      separation of IgG and IgM. The strong anion-exchange column had the highest
      dynamic binding capacity reaching more than 20mg of IgM/ml of support.
      Additionally, separation of IgM from human serum albumin, a common contaminant in
      immunoglobulin purification, was achieved on the weak ethylenediamino anion
      exchange column, which set the basis for the IgM purification method developed on
      convective interaction media (CIM) supports. Experiments also confirmed flow
      independent characteristics of the short monolithic columns.

PMID- 17204273
TI  - Simplified method for determination of polycarbamate fungicide in water samples
      by liquid chromatography with tandem mass spectrometry following derivatization
      with dimethyl sulfate.
AB  - A simple and sensitive analytical method for the determination of polycarbamate
      in water samples was developed. In this method, polycarbamate was cleaved under
      alkaline conditions and derivatized with dimethyl sulfate to methyl
      dimethyldithiocarbamate (DMDC-methyl) and dimethyl ethylenebisdithiocarbamate
      (EBDC-dimethyl). After the solid-phase extraction of the resulting methyl
      derivatives, they were measured by liquid chromatography with tandem mass
      spectrometry (LC-MS/MS), based on reversed-phase separation and MS/MS detection
      with positive atmospheric pressure chemical ionization. The absolute recoveries
      (mean+/-SD) all through the procedure from polycarbamate to DMDC-methyl and EBDC
      dimethyl were 62.6+/-4.3 and 73.5+/-5.9%, respectively. The limits of detection
      and quantification of polycarbamate in the water samples were 0.061 and 0.20
      microg/L in the form of DMDC-methyl, and 0.032 and 0.11 microg/L in the form of
      EBDC-dimethyl, respectively. The method was validated at levels of 0.25, 1.0, and
      5.0 microg/L in the tap water and river water samples, and accuracy was achieved
      in the range of 94-109%. The proposed method can be applied to the determination
      of trace amounts of polycarbamate in environmental water samples.

PMID- 17204274
TI  - A simple and fast method for the simultaneous determination of polychlorinated
      biphenyls and polybrominated diphenyl ethers in small volumes of human serum.
AB  - A fast extraction and clean-up method for the simultaneous determination of PCBs
      and PBDEs has been developed. The procedure consisted of a solid-phase extraction
      (SPE) of the analytes on an Oasis HLB cartridge and the subsequent on-line fat
      elimination by directly dropping the eluate from the SPE cartridge onto a second
      cartridge containing layers of activated neutral silica gel and sulphuric acid
      modified silica gel. Detection limits using a gas chromatography coupled with an
      ion trap detector in the tandem mass spectrometry mode were from 0.03 to 0.3
      pg/microL for PCBs and from 0.07 to 1.3 pg/microL for PBDEs. Repeatability (lower
      than 11%) and reproducibility (lower than 17%), expressed as relative standard
      deviation (RSD, n=4), were satisfactory. The feasibility of the method developed
      for the determination of the target compounds was evaluated by participation in
      several rounds of interlaboratory exercises involving human serum with a wide
      range of PBDE and PCB concentrations. The method has been applied to the
      evaluation of PBDEs and PCBs in human serum samples of up to 1 mL.

PMID- 17204275
TI  - Fast data preprocessing for chromatographic fingerprints of tomato cell wall
      polysaccharides using chemometric methods.
AB  - The variability in the chemistry of cell wall polysaccharides in pericarp tissue
      of red-ripe tomato fruit (Solanum lycopersicon Mill.) was characterized by
      chemical methods and enzymatic degradations coupled to high performance anion
      exchange chromatography (HPAEC) and mass spectrometry analysis. Large fruited
      line, Levovil (LEV) carrying introgressed chromosome fragments from a cherry
      tomato line Cervil (CER) on chromosomes 4 (LC4), 9 (LC9), or on chromosomes 1, 2,
      4 and 9 (LCX) and containing quantitative trait loci (QTLs) for texture traits,
      was studied. In order to differentiate cell wall polysaccharide modifications in
      the tomato fruit collection by multivariate analysis, chromatograms were
      corrected for baseline drift and shift of the component elution time using an
      approach derived from image analysis and mathematical morphology. The baseline
      was first corrected by using a "moving window" approach while the peak-matching
      method developed was based upon location of peaks as local maxima within a window
      of a definite size. The fast chromatographic data preprocessing proposed was a
      prerequisite for the different chemometric treatments, such as variance and
      principal component analysis applied herein to the analysis. Applied to the
      tomato collection, the combined enzymatic degradations and HPAEC analyses
      revealed that the firm LCX and CER genotypes showed a higher proportion of
      glucuronoxylans and pectic arabinan side chains while the mealy LC9 genotype
      demonstrated the highest content of pectic galactan side chains. QTLs on tomato
      chromosomes 1, 2, 4 and 9 contain important genes controlling glucuronoxylan and
      pectic neutral side chains biosynthesis and/or metabolism.

PMID- 17204276
TI  - Room temperature synthesis of HgTe nanocrystals.
AB  - We report a new method to synthesize monodisperse zinc blende HgTe nanocrystals
      at room temperature in noncoordinating solvent-octadecene. Thiol was needed to
      control the reaction at a suitable nucleation and growth speed. In the early
      stage of the reaction, HgTe nanocrystals formed aggregates, and then the
      aggregates were dispersed and individual dot-shaped nanocrystals were formed with
      stronger photoluminescence emitting. UV-vis, photoluminescence, and TEM have been
      used to study the properties of as-prepared HgTe nanocrystals.

PMID- 17204277
TI  - Effect of lead on the sorption of phenol onto montmorillonites and organo
      montmorillonites.
AB  - The effect of lead (Pb) on the sorption of phenol onto montmorillonite-based
      sorbents was studied using a batch equilibration method when phenol and Pb were
      sorbed simultaneously and either Pb or phenol was previously sorbed. The sorbents
      were Na(+)-, Ca(2+)-, hexadecyl trimethylammonium (HDTMA)-Na(+)-, and HDTMA
      Ca(2+)-montmorillonites. Pb diminished the sorption of phenol largely onto Na(+)-
      or Ca(2+)-montmorillonites, while phenol had little effect on the sorption of Pb
      onto all sorbents. Pb had no effect on the sorption of phenol onto HDTMA-Na(+)-
      or HDTMA-Ca(2+)-montmorillonites either. The sorption capacity of phenol followed
      the order HDTMA-Na(+)- > HDTMA-Ca(2+)- > Na(+)- > Ca(2+)-montmorillonites. The
      pseudo-second-order equation described the kinetics of phenol sorption well.
      Sorption isotherms of phenol followed the Freundlich equation. Phenol sorption on
      HDTMA-Na(+)- and HDTMA-Ca(2+)-montmorillonites was linear, while that on Na(+)-
      and Ca(2+)-montmorillonites was nonlinear.

PMID- 17204278
TI  - RBM band shift-evidenced dispersion mechanism of single-wall carbon nanotube
      bundles with NaDDBS.
AB  - The dispersion process of single-wall carbon nanotube (SWNT) by using sodium
      dodecylbenzene sulfonate (NaDDBS) was studied by means of surface tension
      measurements, ultraviolet-visible (UV-Vis) spectroscopy, scanning electron
      microscopy (SEM), and transmission electron spectroscopy (TEM). The critical
      micelle concentration (CMC) and the concentration where the surface tension
      begins to drop increase by the presence of SWNT. The isotherm of NaDDBS amount
      adsorbed on SWNT shows the plateau region at 0.2-6 mM and the saturated region
      above 40 mM. The external surface of SWNT bundle is fully covered with adsorbed
      NaDDBS at the plateau region, showing that SWNTs can be dispersed with the bundle
      form. On the other hand, SWNTs are dispersed in individual tubes at the saturated
      region, where the adsorption amount corresponds to coating of individual tube
      surfaces with NaDDBS. This dispersion state was confirmed by SEM and TEM
      observations. The effect of the dispersion state of SWNTs on radial breathing
      mode in Raman spectrum gave inherent peak shifts, being the in situ evidences on
      the step-wise dispersion mechanism of the SWNT bundle to the individual tubes.

PMID- 17204279
TI  - Formation of protein molecular imprints within Langmuir monolayers: a quartz
      crystal microbalance study.
AB  - Protein imprinting leading to enhanced rebinding of ferritin to ternary lipid
      monolayers is demonstrated using a quartz crystal microbalance. Monolayers
      consisting of cationic dioctadecyldimethylammonium bromide, non-ionic methyl
      stearate, and poly(ethylene glycol) bearing phospholipids were imprinted with
      ferritin at the air/water interface of a Langmuir-Blodgett trough and transferred
      hydrated to hydrophobic substrates for study. This immobilization was shown by
      fluorescence correlation spectroscopy to significantly hinder any further
      diffusion of lipids, while rebinding studies demonstrated up to a six-fold
      increase in ferritin adsorption to imprinted versus control monolayers. A
      diminished rebinding of ferritin to its imprint was observed through pH reduction
      to below the protein isoelectric point, demonstrating the electrostatic nature of
      the interaction. Rebinding to films where imprint pockets remained occupied by
      the template protein was also minimal. Studies with a smaller acidic protein
      revealed the importance of the steric influence of poly(ethylene glycol) in
      forming the protein binding pockets, as albumin-imprinted monolayers showed low
      binding of ferritin, while ferritin-imprinted monolayers readily accommodated
      albumin. The controllable structure-function relationship and limitations of this
      system are discussed with respect to the application of protein imprinting in
      sensor development as well as fundamental studies of proteins at dynamic
      interfaces.

PMID- 17204280
TI  - Surfactant-assistant and facile synthesis of hollow ZnS nanospheres.
AB  - Small and monodisperse ZnS hollow nanospheres with outer diameter ranging from 60
      to 70 nm and wall thickness of 15-20 nm were fabricated in a large scale by a
      simple surfactant polyethylene glycol (PEG) assisted method. The diameter and the
      wall thickness of the hollow nanospheres could be controlled by manipulating the
      amount of PEG and the aging time, respectively. Moreover, the wall of these
      hollow nanospheres is very compact. The product was characterized by X-ray power
      diffraction (XRD), transmission electron microscopy (TEM), UV-vis spectrum and
      fluorescence spectroscopy. The photocatalytic activity of as-prepared ZnS hollow
      nanospheres was also evaluated by using methyl orange (MO) as a model organic
      compound and the result revealed that their photocatalytic activity is a little
      lower than that of Degussa P25 TiO(2) but better than that of ZnS nanocrystals
      prepared by literature method. Furthermore, a rational mechanism to the formation
      and evolution of the products is proposed.

PMID- 17204281
TI  - Direct aerosol synthesis of carboxy-functionalized iron oxide colloids displaying
      reversible magnetic behavior.
AB  - A simple and rapid synthetic strategy for fabricating carboxy-functionalized iron
      oxide colloidal particles displaying reversible magnetic behavior is reported.
      The method is based on the pyrolysis of aerosols generated from ethanol/water
      solutions containing iron inorganic salts and mono- or polysaccharides. Essential
      to the success of the method are the use of hybrid (organo-inorganic) aerosols
      and the temperature of pyrolysis. The resulting material could be used in
      advanced biotechnological applications such as the magnetically assisted chemical
      separation of biocompounds.

PMID- 17204282
TI  - Ionic separation efficiency of a novel electric-field-assisted membrane module
      comprising an array of microchannel units.
AB  - The ionic separation efficiency of a novel membrane module comprising an array of
      microchannel units is analyzed. Under the Debye-Huckel approximation, we derive a
      semianalytical expression for the ionic separation efficiency. Analyses reveal
      that the effects of the size of the microchannel, the fixed charge density in the
      membrane layer, and the permittivity of the membrane layer on ionic separation
      efficiency depend strongly on the valence type of electrolyte in treated water.
      Under the condition of a symmetric electrolyte, the ionic separation efficiency
      is found to be about unity and unresponsive to variation of system parameters. If
      the valence of the cation is higher than that of the anion, the ionic separation
      efficiency is larger than unity, and decreases to unity as the size of the
      microchannel increases. In contrast, if the valence of the cation is lower than
      that of the anion, the ionic separation efficiency is smaller than unity and
      increases to unity as the size of the microchannel increases. Under the latter
      two conditions, the effects of both fixed charge density in the membrane layer
      and permittivity of the membrane layer on the ionic separation efficiency are
      found to be reversed.

PMID- 17204283
TI  - Studies on selenite adsorption using manganese nodule leached residues.
AB  - Selenite adsorption on water-washed manganese nodule leached residues (WMNLR) was
      studied with the aim of detoxifying industrial effluents before their safe
      disposal into the environment. WMNLR, a solid waste material, was characterized
      with the help of XRD, FTIR, TG-DTA, pH(pzc), BET surface area, surface oxygen,
      surface hydroxyl group, and chemical analyses. The adsorption behavior of WMNLR
      toward selenite was studied as a function of time, pH, temperature, and
      concentration of adsorbate and adsorbent. Increased adsorption capacity with rise
      in temperature indicates that the adsorption process was endothermic in nature.
      Based on the thermodynamic parameters such as the Gibbs free energy change,
      standard enthalpy change, and standard entropy change, the adsorption process was
      found to be spontaneous and endothermic in nature. Adsorption followed second
      order kinetics. The adsorption capacity of the material was found to be 54.6 mg
      g(-1) at 60 mg L(-1) of selenite concentration at pH 5 in 3 h contact time.

PMID- 17204284
TI  - Exonization of Alu-generated splice variants in the survivin gene of human and
      non-human primates.
AB  - Survivin is a member of the inhibitor apoptosis family that is overexpressed in
      many malignancies. It has five known alternative splice forms, some of which
      differ in their antiapoptotic properties and expression levels in human cancers.
      Here we describe a novel donor splice site (DSS), 2B+32 DSS, which is used in
      conjunction with survivin alternative exon 2B, resulting in the inclusion of 32
      additional nucleotides from intron 2 at the 3' end of this exon. Sequence
      analysis showed that both the classical exon 2B DSS and 2B+32 are provided by an
      Alu sequence, which is inserted in intron 2 downstream of a functional acceptor
      splice site, leading to the exonization of part of the repetitive element. Minor
      transcripts including the 2B+32 alternative exon, or retaining the whole intronic
      region comprised between exons 2B and 3, were detected in several human cell
      lines and in some human tissues. Survivin 2B+32 containing variants acquire a
      premature stop codon (PTC) and may therefore be degraded by the nonsense mediated
      decay pathway. The implication of these novel isoforms, as well as other PTC+
      survivin variants, in the overall regulation of survivin expression is discussed.
      Sequence analysis of intron 2 which contains the Alu Y element was performed on
      different primate species in order to trace its insertion and exonization during
      primate evolution.

PMID- 17204285
TI  - NMR structural characterization of substrates bound to N
      acetylglucosaminyltransferase V.
AB  - N-Acetylglucosaminyltransferase V (GnT-V) is an enzyme involved in the
      biosynthesis of asparagine-linked oligosaccharides. It is responsible for the
      transfer of N-acetylglucosamine (GlcNAc) from the nucleotide sugar donor, uridine
      5'-diphospho-N-acetylglucosamine (UDP-GlcNAc), to the 6 position of the alpha-1-6
      linked Man residue in N-linked oligosaccharide core structures. GnT-V up
      regulation has been linked to increased cancer invasiveness and metastasis and,
      appropriately, targeted for drug development. However, drug design is impeded by
      the lack of structural information on the protein and the way in which substrates
      are bound. Even though the catalytic domain of this type II membrane protein can
      be expressed in mammalian cell culture, obtaining structural information has
      proved challenging due to the size of the catalytic domain (95 kDa) and its
      required glycosylation. Here, we present an experimental approach to obtaining
      information on structural characteristics of the active site of GnT-V through the
      investigation of the bound conformation and relative placement of its ligands,
      UDP-GlcNAc and beta-D-GlcpNAc-(1-->2)-alpha-D-Manp-(1-->6)-beta-D-GlcpOOctyl.
      Nuclear magnetic resonance (NMR) spectroscopy experiments, inducing transferred
      nuclear Overhauser effect (trNOE) and saturation transfer difference (STD)
      experiments, were used to characterize the ligand conformation and ligand-protein
      contact surfaces. In addition, a novel paramagnetic relaxation enhancement
      experiment using a spin-labeled ligand analogue, 5'-diphospho-4-O-2,2,6,6
      tetramethylpiperidine 1-oxyl (UDP-TEMPO), was used to characterize the relative
      orientation of the two bound ligands. The structural information obtained for the
      substrates in the active site of GnT-V can be useful in the design of inhibitors
      for GnT-V.

PMID- 17204286
TI  - A splice variant of the human CCA-adding enzyme with modified activity.
AB  - The human CCA-adding enzyme (tRNA nucleotidyltransferase) is an essential enzyme
      that catalyzes the addition of the CCA terminus to the 3' end of tRNA precursors,
      a reaction which is a fundamental prerequisite for mature tRNAs to become
      aminoacylated and to participate in protein biosynthesis. To date only one form
      of this enzyme has been identified in humans. Here, we describe the sequence and
      activity of a splice variant of the human CCA-adding enzyme identified in public
      cDNA databases. The in silico analyses performed on this splice variant indicate
      that there is conservation of the alternative splice donor site among species and
      indicate that it seems to be used in vivo. Moreover, the recombinantly expressed
      protein is active in vitro and accepts tRNA transcripts as substrates
      incorporating the dinucleotide sequence CC to their 3' end, in contrast to the
      activity of the full length enzyme. These findings strongly suggest that the
      splice variant of the human CCA-adding enzyme is expressed in the cell although
      the in vivo function remains unclear.

PMID- 17204287
TI  - Early kinetics of amyloid fibril formation reveals conformational reorganisation
      of initial aggregates.
AB  - Understanding the initial steps of protein aggregation leading to the formation
      of amyloid fibrils remains a challenge. Here, the kinetics of such a process is
      determined for a misfolding protein model, ADA2h. The double nature of the very
      early kinetics suggests a step model of aggregation, where the denatured
      polypeptide folds into an aggregated beta-intermediate that subsequently
      reorganises into a more organised beta-sheet-richer structure that finally
      results in amyloid fibre formation. To determine the regions of the protein
      involved in amyloidosis, we have analysed a series of mutants previously made to
      study ADA2h folding. Using the algorithm TANGO, we have designed mutants that
      should enhance or decrease aggregation. Experimental analysis of the mutants
      shows that the C terminus of the molecule (comprising the last and edge beta
      strand) is the major contributor to amyloid fibril formation, in good agreement
      with theoretical predictions. Comparison with proteins with similar topology
      reveals that family folds do not necessarily share the same principles of protein
      folding and/or aggregation.

PMID- 17204288
TI  - Contribution of initial heart rate to the prediction of posttraumatic stress
      symptom level in accident victims.
AB  - Earlier findings of a positive correlation between heart rate (HR) and
      posttraumatic symptom level have recently been brought into question. Therefore,
      we investigated the relationship between resting HR and symptom scores of
      posttraumatic stress disorder (PTSD) in physically injured accident survivors,
      controlling for well established predictors for (PTSD and factors influencing HR.
      A representative sample of 255 accident victims was assessed measuring PRIME-MD,
      PDEQ, trauma-related cognitions and CAPS. Initial interviews were conducted five
      days post trauma; follow-up assessments took place six months later. Heart rate
      measurements were obtained from surgical files. We found positive bivariate
      correlations between HR at hospital admission (HRA) and PTSD symptom levels.
      However, in multiple regression analysis HRA contributed marginally to the
      prediction of PTSD symptom levels. We conclude that the initial heart rate is a
      weak and not independent predictor for PTSD symptom level following accidental
      injuries.

PMID- 17204289
TI  - Spousal concordance for substance use and anxiety disorders.
AB  - Assortative mating -- the tendency for mate selection to occur on the basis of
      similar traits -- plays an essential role in understanding the genetic
      contribution to psychiatric illness. It also carries significant impact on
      clinical prognosis and is an important mechanism explaining spousal concordance.
      This study uses a family study design ascertaining 225 probands with substance
      abuse/dependence, anxiety disorders, and controls to address: (1) Is there
      spousal concordance or cross-concordance for substance use and/or anxiety
      disorders? (2) Is the spousal concordance or cross-concordance associated with
      worse clinical outcomes? (3) What is the mechanism of the concordance or cross
      concordance? Results show a high magnitude of spousal concordance for substance
      use disorders with a third of the substance probands' spouses also substance
      dependent. In contrast, there was no spousal concordance for anxiety disorders.
      Couples were also concordant for having "no disorders." Both substance use and
      anxiety disorder concordance were associated with poorer global functioning and
      persistent illness. Assortative mating is a likely mechanism for spousal
      concordance given the elevated rate of substance use disorders among the
      relatives of spouses' of substance probands. Implications for family/genetic
      studies and the transmission of substance use disorders and "no disorders"
      include: (1) at the individual level, spousal concordance influences probands'
      course of illness, couples' marital functioning, and offspring's genetic and
      environmental context; and (2) at the population level, it shifts the general
      distribution of substance use disorders and "no disorders" by reducing the
      "average" couple concordance and increasing the number concordant and discordant
      couples at extremes of the distribution.

PMID- 17204290
TI  - Superstability of the yeast cell-cycle dynamics: ensuring causality in the
      presence of biochemical stochasticity.
AB  - Gene regulatory dynamics are governed by molecular processes and therefore
      exhibits an inherent stochasticity. However, for the survival of an organism it
      is a strict necessity that this intrinsic noise does not prevent robust
      functioning of the system. It is still an open question how dynamical stability
      is achieved in biological systems despite the omnipresent fluctuations. In this
      paper we investigate the cell cycle of the budding yeast Saccharomyces cerevisiae
      as an example of a well-studied organism. We study a genetic network model of 11
      genes that coordinate the cell-cycle dynamics using a modeling framework which
      generalizes the concept of discrete threshold dynamics. By allowing for
      fluctuations in the process times, we introduce noise into the model, accounting
      for the effects of biochemical stochasticity. We study the dynamical attractor of
      the cell cycle and find a remarkable robustness against fluctuations of this
      kind. We identify mechanisms that ensure reliability in spite of fluctuations:
      'Catcher states' and persistence of activity levels contribute significantly to
      the stability of the yeast cell cycle despite the inherent stochasticity.

PMID- 17204291
TI  - Stochastic Markovian modeling of electrophysiology of ion channels:
      reconstruction of standard deviations in macroscopic currents.
AB  - Markovian models of ion channels have proven useful in the reconstruction of
      experimental data and prediction of cellular electrophysiology. We present the
      stochastic Galerkin method as an alternative to Monte Carlo and other stochastic
      methods for assessing the impact of uncertain rate coefficients on the
      predictions of Markovian ion channel models. We extend and study two different
      ion channel models: a simple model with only a single open and a closed state and
      a detailed model of the cardiac rapidly activating delayed rectifier potassium
      current. We demonstrate the efficacy of stochastic Galerkin methods for computing
      solutions to systems with random model parameters. Our studies illustrate the
      characteristic changes in distributions of state transitions and electrical
      currents through ion channels due to random rate coefficients. Furthermore, the
      studies indicate the applicability of the stochastic Galerkin technique for
      uncertainty and sensitivity analysis of bio-mathematical models.

PMID- 17204292
TI  - Endogenous angiotensin II enhances atherogenesis in apoprotein E-deficient mice
      with renovascular hypertension through activation of vascular smooth muscle
      cells.
AB  - Renovascular hypertension is one of the most important risk factors in the
      development of atherosclerosis. However, very little is known about the role of
      angiotensin II (AII), a key regulator of blood pressure homeostasis, on
      renovascular hypertension-associated atherogenesis. To study a possible role of
      AII on atherogenesis, we generated apoE-deficient hypertensive mice with either
      normal or increased AII production by applying 1-kidney, 1-clip (1K1C) or 2
      kidney, 1-clip (2K1C) operation, respectively. Hypertension was successfully
      achieved in both mice groups, and was persistent for 8 weeks. Atherosclerosis
      quantification showed a marked increase in lesion area in aortic sinus of 2K1C
      mice as compared with 1K1C mice, suggesting a potential role of endogenous AII on
      atherogenesis. In the immunohistochemical analysis, induction of renovascular
      hypertension with 2K1C for 8 weeks led to an enhanced accumulation of macrophages
      in the aortic sinus, which was accompanied by a parallel increase in scavenger
      receptor A (SRA) expression on the macrophages. In in vitro experiments, although
      treatment of cells with increasing concentrations of AII (0.1 to 10 microM)
      affects neither SRA expression nor oxLDL uptake by macrophages, conditioned media
      (CM) derived from AII-stimulated vascular smooth muscle cells (VSMC) increased
      macrophage uptake of oxLDL in association with an enhanced expression of SRA on
      the macrophages. These findings suggest that the increased generation of AII in
      renovascular hypertension may initiate and promote atherosclerosis by activation
      of VSMC.

PMID- 17204293
TI  - The effects of biscoclaurine alkaloid cepharanthine on mammalian cells:
      implications for cancer, shock, and inflammatory diseases.
AB  - The extract of Stephania cepharantha Hayata contains biscoclaurine alkaloids such
      as cepharanthine, which have been used widely in Japan for the treatment of
      patients with radiation-induced leukopenia, alopecia areata, exudative otitis
      media, and venomous snakebites. Many investigations have proven that the alkaloid
      cepharanthine exerts diverse pharmacological effects that include membrane
      stabilizing, multidrug resistance-reversing, antitumor, apoptosis-inducing, anti
      inflammatory, free radical scavenging, anti-HIV-1, antiallergic and
      immunomodulatory effects. The purpose of our review is to describe various
      therapeutic approaches using cepharanthine and their potential efficacy.

PMID- 17204294
TI  - The flavonoid baicalin protects against cerebrovascular dysfunction and brain
      inflammation in experimental heatstroke.
AB  - The present study was performed to assess the prophylactic effect of baicalin, a
      flavonoid compound, in an animal model of heatstroke. Anesthetized rats,
      immediately before the start of heat stress, were divided into two major groups
      and given the following: vehicle solution (1mL per kg body weight) or baicalin
      (10-40mg per kg body weight) intravenously. They were exposed to ambient
      temperature of 43 degrees C to induce heatstroke. Another group of rats was
      exposed to room temperature (24 degrees C) and used as normothermic controls.
      Their physiologic and biochemical parameters were continuously monitored. When
      the vehicle-pretreated rats underwent heat stress, their survival time values
      were found to be 20-28min. Pretreatment with intravenous doses of baicalin
      significantly improved survival during heatstroke (65-248min). As compared to
      those of normothermic controls, all vehicle-pretreated heatstroke animals
      displayed higher levels of core temperature, intracranial pressure, and nitric
      oxide metabolite (NO(2)(-)), glutamate, glycerol, lactate/pyruvate ratio, and
      dihydroxybenzoic acid (DHBA) in hypothalamus. In addition, both serum and
      hypothalamic levels of interleukin-1beta (IL-1beta) and tumor necrosis factor
      alpha (TNF-alpha) as well as plasma levels of creatinine, serum urea nitrogen,
      glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline
      phosphatase were elevated after heatstroke onset. In contrast, all vehicle
      pretreated heatstroke animals had lower levels of mean arterial pressure,
      cerebral perfusion pressure, cerebral blood flow, and brain PO(2). Administration
      of baicalin before the start of heat exposure significantly reduced the
      hyperthermia, intracranial hypertension, and the increased levels of NO(2)(-),
      glutamate, glycerol, lactate/pyruvate ratio, and DHBA in the hypothalamus that
      occurred during heatstroke. The heatstroke-induced increased levels of IL-1beta
      and TNF-alpha in both the serum and hypothalamus, and renal and hepatic
      dysfunction were suppressed by baicalin pretreatment. In contrast, both the serum
      and hypothalamic levels of IL-10 were significantly elevated by baicalin during
      heatstroke. We successfully demonstrated that baicalin can be used as a
      prophylactic agent for heatstroke. In particular, baicalin may protect against
      cerebrovascular dysfunction and brain inflammation in heatstroke.

PMID- 17204295
TI  - Neural correlates of processing facial identity based on features versus their
      spacing.
AB  - Adults' expertise in recognizing facial identity involves encoding subtle
      differences among faces in the shape of individual facial features (featural
      processing) and in the spacing among features (a type of configural processing
      called sensitivity to second-order relations). We used fMRI to investigate the
      neural mechanisms that differentiate these two types of processing. Participants
      made same/different judgments about pairs of faces that differed only in the
      shape of the eyes and mouth, with minimal differences in spacing (featural
      blocks), or pairs of faces that had identical features but differed in the
      positions of those features (spacing blocks). From a localizer scan with faces,
      objects, and houses, we identified regions with comparatively more activity for
      faces, including the fusiform face area (FFA) in the right fusiform gyrus, other
      extrastriate regions, and prefrontal cortices. Contrasts between the featural and
      spacing conditions revealed distributed patterns of activity differentiating the
      two conditions. A region of the right fusiform gyrus (near but not overlapping
      the localized FFA) showed greater activity during the spacing task, along with
      multiple areas of right frontal cortex, whereas left prefrontal activity
      increased for featural processing. These patterns of activity were not related to
      differences in performance between the two tasks. The results indicate that the
      processing of facial features is distinct from the processing of second-order
      relations in faces, and that these functions are mediated by separate and
      lateralized networks involving the right fusiform gyrus, although the FFA as
      defined from a localizer scan is not differentially involved.

PMID- 17204296
TI  - Characterization and engineering of glycosyltransferases responsible for steroid
      saponin biosynthesis in Solanaceous plants.
AB  - Solanaceous plants contain steroid saponins that have diverse biological and
      pharmacological activities. The structures of their sugar chains play an
      important role in their activities. A functional glucosyltransferase SaGT4A from
      Solanum aculeatissimum glucosylates both steroidal sapogenins and steroidal
      alkaloids. A potato (S. tuberosum) glycosyltransferase StSGT, which has a high
      degree of sequence homology with SaGT4A, exhibits the same substrate specificity
      toward steroidal compounds as SaGT4A. To identify the residues or domain
      structures responsible for these enzymatic activities, we determined the residues
      that are essential for SaGT4A activity, compared the specific activities of
      SaGT4A and StSGT, and constructed several SaGT4A/StSGT chimeric proteins,
      focusing on the donor-sugar recognition domain. These proteins were
      heterogeneously expressed in E. coli and purified, and their glycosyltransferase
      activities were evaluated using a coupled assay. His369 and Glu377, located in
      the consensus motif for plant glycosyltransferases, and Cys121, Cys247, and
      Cys370 were shown to be important for SaGT4A activity. StSGT exhibited more
      activity with UDP-galactose as a sugar donor than with UDP-glucose, whereas
      SaGT4A exhibited glucosyltransferase activity exclusively. The sugar
      selectivities of SaGT4A and StSGT were not altered by exchanging their domains,
      and some of the chimeric proteins showed no activity. These results suggest that
      the differences in the SaGT4A and StSGT amino acid sequences do not simply
      reflect their distinct sugar-donor specificities. We also successfully converted
      the non-functional SaGT4A homolog, SaGT4R, into an active glucosyltransferase.

PMID- 17204297
TI  - Estimates of short- and long-term incubation periods of Plasmodium vivax malaria
      in the Republic of Korea.
AB  - With the current epidemic of vivax malaria closely associated with the
      demilitarised zone along the border between North and South Korea, it has been
      suggested that the incubation period tends, in part, to be prolonged. Based on
      the detailed travel history of cases from 2000 to 2003 who reside in non
      malarious areas, statistical estimates of the incubation periods were obtained.
      The data suggest that cases fall into two categories with short- and long-term
      incubation periods, respectively. Of 416 cases with available information, 72 and
      79 successfully met our criteria for inferring the durations of short- and long
      term incubation periods. The mean short- and long-term incubation periods were
      estimated to be 26.6 days (95% CI 21.0-32.2) and 48.2 weeks (95% CI 46.8-49.5),
      respectively. The maximum likelihood method was used to fit gamma and normal
      distributions to the short- and long-term incubation periods, assisting
      prediction of the frequency distribution of the overall incubation period, which
      exhibited a bimodal pattern. We postulate that the observed distribution reflects
      adaptation of the parasite to the seasonal population dynamics of the vector,
      Anopheles sinensis, ensuring continued transmission of vivax malaria in this
      temperate zone.

PMID- 17204298
TI  - Atrazine-induced reproductive tract alterations after transplacental and/or
      lactational exposure in male Long-Evans rats.
AB  - Studies showed that early postnatal exposure to the herbicide atrazine (ATR)
      delayed preputial separation (PPS) and increased incidence of prostate
      inflammation in adult Wistar rats. A cross-fostering paradigm was used in this
      study to determine if gestational exposure to ATR would also result in altered
      puberty and reproductive tissue effects in the male rat. Timed-pregnant Long
      Evans (LE) rats were dosed by gavage on gestational days (GD) 15-19 with 100 mg
      ATR/kg body weight (BW) or 1% methylcellulose (controls, C). On postnatal day
      (PND)1, half litters were cross-fostered, creating 4 treatment groups; C-C, ATR
      C, C-ATR, and ATR-ATR (transplacental-milk as source, respectively). On PND4,
      male offspring in the ATR-ATR group weighed significantly less than the C-C
      males. ATR-ATR male pups had significantly delayed preputial separation (PPS).
      BWs at PPS for C-ATR and ATR-ATR males were reduced by 6% and 9%, respectively,
      from that of C-C. On PND120, lateral prostate weights of males in the ATR-ATR
      group were significantly increased over C-C. Histological examination of lateral
      and ventral prostates identified an increased distribution of inflammation in the
      lateral prostates of C-ATR males. By PND220, lateral prostate weights were
      significantly increased for ATR-C and ATR-ATR, but there were no significant
      changes in inflammation in either the lateral or ventral prostate. These results
      suggest that in LE rats, gestational ATR exposure delays PPS when male offspring
      suckle an ATR dam, but leads to increased lateral prostate weight via
      transplacental exposure alone. Inflammation present at PND120 does not increase
      in severity with time.

PMID- 17204299
TI  - Role of cyclooxygenases in oedema-forming activity of bothropic venoms.
AB  - The venoms of Bothrops asper (BaV) and Bothrops jararaca (BjV), two of the most
      medically important poisonous snakes of Latin America, cause pronounced oedema in
      the victims through poorly understood mechanisms. In the present study, we
      examined the possible role of cyclooxygenases (COX) in the genesis of mouse paw
      oedema caused by BaV and BjV injections. BaV at 2.5 microg/paw and BjV at 0.75
      microg/paw induced significant oedema that persisted for up to 6h following
      subplantar injection. Treatment with indomethacin (2 mg/kg), rofecoxib, (10
      mg/kg), or dexamethasone (2 mg/kg) significantly reduced the BaV- and BjV-induced
      oedema formation. Treatment with SC-560 (30 mg/kg) significantly reduced the
      oedema formation induced by BjV but had no effect on that induced by BaV. Both
      venoms induced significant increases in the levels of prostaglandin E(2) (PGE(2))
      and the expression of COX-1 and COX-2 in paw tissue. The peak of oedema formation
      and PGE(2) release correlated with marked expression of COX-2 in the paw tissue.
      These results demonstrate that injection of BaV and BjV results in a rapid
      increase in oedema formation that is, at least partially, mediated by arachidonic
      acid metabolites formed by COX-2. In the case of BjV, COX-1-derived prostanoids
      also appear to contribute significantly to the inflammatory changes.

PMID- 17204300
TI  - Retention of inorganic arsenic by coryneform mutant strains.
AB  - The natural resistance mechanisms of corynebacteria to respond to the
      environments containing high levels of arsenic were successfully adopted to
      develop inexpensive and selective extractants for submicrogram amounts of
      arsenic. Kinetic and equilibrium characteristics were evaluated, and a
      preliminary exploration of the capability of these strains to be used for arsenic
      speciation was also made in this work. Three kinetics models were used to fit the
      experimental data. It was found that the pseudo-first-order kinetics model was
      not quite adequate to describe the retention process, while the intraparticle
      diffusion and the pseudo-second-order kinetics models provide the best fits. The
      equilibrium isotherm showed that the retention of arsenic was consistent with the
      Langmuir equation and that the Freundlich and Dubinin-Radushkevich models
      provided poorer fits to the experimental data. The maximum effective retention
      capacity for arsenic was about 15.4 ng As/mg biomass. The amount of arsenic
      retained was directly measured in the biomass by forward planning a slurry
      electrothermal atomic absorption spectrometric procedure.

PMID- 17204301
TI  - Removing nitric oxide from flue gas using iron(II) citrate chelate absorption
      with microbial regeneration.
AB  - The addition of metal chelates such as Fe(II)EDTA or Fe(II)Cit to wet flue gas
      desulfurization systems has been shown to increase the amount of NO(x) absorption
      from gas streams containing SO(2). This paper attempts to demonstrate the
      advantage of not only using Fe(II)Cit chelate to absorb nitrogen oxides from flue
      gas but also the advantage gained from adding microorganisms to the system. Two
      distinct classes of microorganisms are needed: denitrifying and iron-reducing
      bacteria. The presence of oxygen in flue gas will affect the absorption
      efficiency of NO by Fe(II)Cit chelate. The oxidation of Fe(II) can be slowed with
      the help of bacteria in two ways: bacteria can serve to directly reduce Fe(III)
      to Fe(II) or they can serve to keep levels of dissolved oxygen in the solution
      low. As a result, after NO absorption, Fe(II)(Cit)NO will be reduced by
      denitrifying bacteria to Fe(II)Cit while Fe(III) is reduced by anaerobic bacteria
      back to Fe(II). Our experiments have shown that the implementation of our
      protocol allowed for an NO reduction rate constant increase from standard levels
      of 0.0222-0.100 m Mh(-1) with inlet NO changed from 250 to 1000 ppm. We have also
      found that total Fe concentration tends to decrease after prolonged periods of
      operation due to the loss of some Fe to the formation of Fe(OH)(3) that settles
      together with the sludge at the bottom of bioreactor tank.

PMID- 17204302
TI  - Metal catalyzed formation of chlorinated aromatic compounds: a study of the
      correlation pattern in incinerator fly ash.
AB  - Chlorinated aromatics are unintentionally formed and released from combustion and
      other thermal processes involving organic matter and chlorine. The catalytic
      activity of incinerator fly ash in the low-temperature formation of chlorinated
      aromatics has been demonstrated in both laboratory experiments and full-scale
      trials. Copper has been shown to be an effective catalyst, but several other
      transition metals possess a similar activity. Here results are reported from a
      series of full-scale combustion trials with different fractions of household and
      industrial wastes, with waste from forestry as a reference fuel. The composition
      of elements and chlorinated aromatics in the fly ash was evaluated with principal
      component analysis and partial least squares regression. The observed correlation
      pattern indicates that metals other than copper are of equal importance for the
      catalytic activity. Chromium and nickel are two of these metals, which may
      contribute to the de novo formation of chlorinated benzenes, phenols, PCDD and
      PCDF.

PMID- 17204303
TI  - The dissipation and transport of veterinary antibiotics in a sandy loam soil.
AB  - The environmental fate of the antibiotics sulfachloropyridazine and
      oxytetracycline was investigated in a sandy loam soil. Liquid pig manure was
      fortified with the compounds and then applied to soil plots to investigate
      leaching, dissipation and surface run-off under field conditions. Additionally,
      as the macrolide antibiotic tylosin had been administered to the pigs from which
      the slurry had been sourced, this was also analysed for in the samples collected.
      Sulfachloropyridazine dissipated rapidly with DT(50) and DT(90) values of 3.5 and
      18.9 days but oxytetracycline was more persistent with DT(50) and DT(90) values
      of 21.7 and 98.3 days. Both sulfachloropyridazine and oxytetracyline were
      detected in surface run-off samples at maximum concentrations of 25.9 and
      0.9microg/l respectively but only sulfachloropyridazine was detected in soil
      water samples at a maximum concentration of 0.78microg/l at 40cm depth 20 days
      after treatment. Tylosin was not detected in any soil or water samples. The
      results indicated that tylosin, when applied in slurry, posed very little risk of
      accumulating in soil or contaminating ground or surface water. However, tylosin
      may pose a risk if used to treat animals on pasture and risks arising from
      transformation products of tylosin, formed during slurry storage, cannot be ruled
      out. Oxytetracycline posed a very low risk of ground or surface water
      contamination but had the potential to persist in soils and sulfachloropyridazine
      posed a moderate risk of contaminating ground or surface water but had low
      potential to accumulate in soils. These findings were consistent with the
      sorption and persistence characteristics of the compounds and support a number of
      broad-scale monitoring studies that have measured these antibiotic classes in the
      environment.

PMID- 17204304
TI  - Cleaner co-combustion of lignite-biomass-waste blends by utilising inhibiting
      compounds of toxic emissions.
AB  - In this paper, the co-combustion behaviour of coal with wastes and biomass and
      the related toxic gaseous emissions were investigated. The objective of this work
      is to add on towards a cleaner co-combustion of lignite-waste-biomass blends by
      utilizing compounds that could inhibit the formation of toxic pollutants. A
      series of co-combustion tests was performed in a pilot scale incinerator, and the
      emissions of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs)
      were measured. The co-combustion behaviour of lignite with olive kernels, MDF and
      sawdust was studied and the ability of additives such as urea, almond shells and
      municipal sewage sludge to reduce the PCDD/F emissions was examined. All blends
      were proven good fuels and reproducible combustion conditions were achieved. The
      addition of inhibitors prior to combustion showed in some cases, relatively high
      PCDD/F emissions reduction. Among the inhibitors tested, urea seems to achieve a
      reduction of PCDD/F emissions for all fuel blends, while an unstable behaviour
      was observed for the others.

PMID- 17204305
TI  - Isolation and characterization of 1,2,4-trichlorobenzene mineralizing Bordetella
      sp. and its bioremediation potential in soil.
AB  - A soil which has been polluted with chlorinated benzenes for more than 25 years
      was used for isolation of adapted microorganisms able to mineralize 1,2,4
      trichlorobenzene (1,2,4-TCB). A microbial community was enriched from this soil
      and acclimated in liquid culture under aerobic conditions using 1,2,4-TCB as a
      sole available carbon source. From this community, two strains were isolated and
      identified by comparative sequence analysis of their 16S-rRNA coding genes as
      members of the genus Bordetella with Bordetella sp. QJ2-5 as the highest
      homological strain and with Bordetella petrii as the closest related described
      species. The 16S-rDNA of the two isolated strains showed a similarity of 100%.
      These strains were able to mineralize 1,2,4-TCB within two weeks to approximately
      50% in liquid culture experiments. One of these strains was reinoculated to an
      agricultural soil with low native 1,2,4-TCB degradation capacity to investigate
      its bioremediation potential. The reinoculated strain kept its biodegradation
      capability: (14)C-labeled 1,2,4-TCB applied to this inoculated soil was
      mineralized to about 40% within one month of incubation. This indicates a
      possible application of the isolated Bordetella sp. for bioremediation of 1,2,4
      TCB contaminated sites.

PMID- 17204306
TI  - Emission of N2O and CH4 from a constructed wetland in southeastern Norway.
AB  - The Skjonhaug constructed wetland (CW) is a free surface water (FSW) wetland
      polishing chemically treated municipal wastewater in southeastern Norway and
      consists of three ponds as well as trickling, unsaturated filters with light
      weight aggregates (LWA). Fluxes of nitrous oxide (N(2)O) and methane (CH(4)) have
      been measured during the autumn, winter and summer from all three ponds as well
      as from the unsaturated filters. Physicochemical parameters of the water have
      been measured at the same localities. The large temporal and spatial variation of
      N(2)O fluxes was found to cover a range of -0.49 to 110 mg N(2)O-N m(-2) day(-1),
      while the fluxes of CH(4) was found to cover a range of -1.2 to 1900 mg m(-2)
      day(-1). Thus, both emission and consumption occurred. Regarding fluxes of N(2)O
      there was a significant difference between the summer, winter and autumn, with
      the highest emissions occurring during the autumn. The fluxes of CH(4) were, on
      the other hand, not significantly different with regard to seasons. Both the
      emissions of N(2)O and CH(4) were positively influenced by the amount of total
      organic carbon (TOC). The measured fluxes of N(2)O and CH(4) are in the same
      range as those reported from other CWs treating wastewater. There was an
      approximately equal contribution to the global warming potential from N(2)O and
      CH(4).

PMID- 17204307
TI  - Heavy metal partitioning from electronic scrap during thermal End-of-Life
      treatment.
AB  - Samples of identical Printed Wiring Board Assemblies (PWBA) have been thermally
      treated in a Quartz Tube Reactor (QTR) in order to detect the volatility of
      selected heavy metals contained in electronic scrap being of environmental
      concern. In preparation, evaporation experiments were performed using a Thermo
      Gravimeter (TG) in connection with an Inductively Coupled Plasma-Optical
      Emissions Spectrometer (ICP-OES). The QTR experiments were performed under
      reducing and under oxidising conditions at 550 and at 880 degrees C. The
      volatilisation has been determined for As, Cd, Ni, Ga, Pb, and Sb using ICP-OES
      analysis of the ash residues. The results were evaluated by thermodynamic
      equilibrium calculations, the TG-ICP measurements and in comparison with similar
      studies. In coincidence with the preparative TG-ICP measurements as well as with
      thermodynamic equilibrium calculations neither As nor Cd could be detected in the
      residuals of the thermally treated PWBA samples, suggesting a high volatility of
      these metals. Ga does not show a distinct volatilisation mechanism and seems to
      be incorporated in the siliceous fraction. Ni remains as stable compound in the
      bottom ash. Sb shows a high volatility nearly independent of temperature and
      oxygen supply. The results imply that, if electronic scrap is thermally
      processed, attention has to be paid in particular to Sb, As, and Ga. These metals
      are increasingly used in new electronic equipment such as mobile phone network
      equipment of the third generation.

PMID- 17204308
TI  - Statin therapy does not seem to benefit giant cell arteritis.
AB  - OBJECTIVE: Since statins interfere with a variety of immune-inflammatory pathways
      shared by atherosclerosis and giant cell arteritis (GCA), they might be
      potentially useful as adjunctive therapy to glucocorticosteroids in GCA. Our aim
      was to examine whether concomitant use of statins had any potential benefit in
      GCA. METHODS: Retrospective follow-up study of an unselected population of 121
      patients with GCA. A comparative analysis between patients with and without
      statin therapy was performed. RESULTS: At the time of the GCA diagnosis, 30
      patients (25%) had already been receiving statins and continued taking them
      during the corticosteroid treatment. No statistically significant reduction in
      the incidence of severe ischemic complications (including visual manifestations,
      jaw claudication, cerebrovascular accidents, ischemic heart disease, and limb
      claudication due to large artery stenosis) was observed in this group compared
      with the remaining patients. When we analyzed follow-up data, we found no
      significant differences between groups in terms of frequency of relapses,
      incidence of aortitis, and percentage of patients recovered from GCA. The
      duration of therapy and corticosteroids requirements among patients in permanent
      remission was similar in both groups. CONCLUSION: We did not observe a
      significant benefit derived from the use of statins at low to moderate doses in
      the incidence of severe ischemia or the disease outcome.

PMID- 17204309
TI  - Determinants of pulmonary arterial hypertension in scleroderma.
AB  - OBJECTIVE: To define risk factors associated with pulmonary arterial hypertension
      (PAH) in a large cohort of patients with systemic sclerosis (SSc). METHODS: SSc
      patients undergoing screening for PAH by means of Doppler echocardiography were
      identified and their charts were retrospectively reviewed. In all patients, we
      recorded systolic pulmonary artery pressure along with pulmonary function
      testing, clinical, and laboratory data. PAH was defined as right ventricular
      systolic pressure equal or greater than 40 mm Hg. RESULTS: Of 114 SSc patients
      with echocardiographic measurements, PAH was found in 33 (29%) patients. In a
      multiple logistic regression analysis, the presence of pulmonary fibrosis on
      thoracic computed tomography (OR 6.78, CI 1.54 to 29.9), forced vital capacity
      less than 80% predicted (OR 3.03, CI 1.1 to 8.35), and duration of Raynaud's
      phenomenon preceding the onset of skin changes for at least 3 years (OR 5.75, CI
      1.9 to 17.41) were found to be independent predictors of PAH. Age, disease
      duration, disease subtype, or autoantibodies were not associated with PAH in our
      patients. CONCLUSIONS: The present analysis identified pulmonary fibrosis and
      Raynaud's phenomenon preceding SSc skin manifestations by at least 3 years as
      risk factors for PAH in our scleroderma cohort. Screening for PAH in these high
      risk patients may detect PAH at an earlier stage and guide decisions on
      therapeutic interventions.

PMID- 17204310
TI  - Patients with rheumatoid arthritis undergoing surgery: how should we deal with
      antirheumatic treatment?
AB  - OBJECTIVES: To review published data on the perioperative management of
      antirheumatic treatment and perioperative outcome in patients with rheumatoid
      arthritis (RA). METHODS: The review is based on a MEDLINE (PubMed) search of the
      English-language literature from 1965 to 2005, using the index keywords
      "rheumatoid arthritis" and "surgery". As co-indexing terms the different disease
      modifying antirheumatic drugs (DMARDs) as well as nonsteroidal anti-inflammatory
      drugs (NSAIDs) and "glucocorticoids" were used. In addition, citations from
      retrieved articles were scanned for additional references. Furthermore, because
      the number of published articles is so limited, relevant abstracts presented at
      congresses were included in the analysis. RESULTS: Continuation of methotrexate
      (MTX) appears to be safe in the perioperative period. Only a limited number of
      studies address the use of leflunomide and the results are conflicting. Because
      of the very long drug half-life, its discontinuation would need to be of long
      duration and is probably not necessary. Data on hydroxychloroquine do not show
      increased risks of infection. Regarding sulfasalazine, there are no studies from
      which definite answers could be drawn on whether it should be withheld
      perioperatively. Preliminary data show that the risk of infections during
      treatment with TNF-blocking agents may be lower than initially expected. The only
      available recommendation (Club Rhumatismes et Inflammation, CRI) suggests
      discontinuing the drugs before surgery for several weeks, depending on the risk
      of infection and the drug used. They should not be restarted until wound healing
      is complete. To avoid the antiplatelet effect during surgery, NSAIDs other than
      aspirin should be withheld for a duration of 4 to 5 times the drug half-life.
      Patients with chronic glucocorticoid therapy and suppressed hypothalamic
      pituitary-adrenal (HPA) axis need perioperative supplementation. CONCLUSIONS:
      While continuation of MTX likely is safe, data on other DMARDs are sparse. In
      particular, more data on the perioperative use of the biologic agents are needed.

PMID- 17204311
TI  - Lifetime cigarette smoke and second-hand smoke and cervical intraepithelial
      neoplasm--a community-based case-control study.
AB  - BACKGROUND: Both active cigarette smoking and human papillomavirus (HPV)
      infection are known risk factors for cervical intraepithelial neoplasm (CIN). The
      association between second-hand smoke (SHS) and CIN has not been conclusively
      determined. We conducted a community-based case-control study to estimate the
      relationship between SHS and CIN. METHODS: Potential study subjects were selected
      through Pap smear screening in Kaohsiung County, Taiwan. A total of 171 subjects
      with either their first case of inflammation (benign epithelial lesion) or > or =
      CIN1 by biopsy confirmation were assigned to a case group; 513 normal subjects
      with negative findings by Pap smears or biopsies were assigned to a control
      group. RESULTS: Non-smoking women exposed to more than 20 pack-years of cigarette
      smoke had a significantly greater risk of developing > or = CIN2 than unexposed
      non-smokers (adjusted OR=7.2, 95% CI=2.5-20.6). Among the women without HPV
      infections, the greater the severity of disease found in the groups (normal,
      inflammation, CIN1, to > or = CIN2), the more likely it was for the women to be
      exposed to SHS, a significant increasing trend (p=0.037). CONCLUSIONS: In
      addition to HPV infection and active cigarette smoking, exposure to SHS is a
      major risk factor for CIN among Taiwanese women.

PMID- 17204312
TI  - The lysophosphatidic acid (LPA) receptors their expression and significance in
      epithelial ovarian neoplasms.
AB  - OBJECTIVE: To investigate the lysophosphatidic acid (LPA) receptors expression
      situation and their biological significance in human ovarian cancer cell lines
      and in human epithelial ovarian neoplasms. METHODS: The reverse transcription
      polymerase chain reaction (RT-PCR) and Western blotting were employed to measure
      the expression levels of LPA(1), LPA(2) and LPA(3) mRNA, LPA(2) and LPA(3)
      protein expression in cultured human ovarian cancer cell lines (3AO, SKOV3 and
      OVCAR3) and in human epithelial ovarian neoplasms. The immunocytochemical method
      was used to detect LPA(2) and LPA(3) protein expression in cultured human ovarian
      cancer cell lines. RESULTS: RT-PCR revealed that all ovarian cancer cell lines
      expressed LPA(1), LPA(2) and LPA(3) mRNA. The positive rates (100%; 86.4%; 88.2%)
      of LPA(1) mRNA in normal ovarian tissue, benign tumor and ovarian cancer were no
      significant difference (p>0.05). The expression level of LPA(1) mRNA was
      significantly higher in normal ovarian tissue compared with that in benign tumor
      and in ovarian cancer tissue (p<0.01). LPA(1) expression level was no significant
      difference in both benign tumor and ovarian cancer tissue (p>0.05). LPA(2) mRNA
      positive rates (92.6%) and expression level were significantly higher in ovarian
      cancer compared with that in benign tumor (31.8%) and in normal ovarian tissue
      (31.3%) (p<0.01); LPA(2) mRNA-positive rates and expression level were no
      significant difference in both benign tumor and normal ovarian tissue (p>0.05).
      LPA(3) mRNA-positive rates (92.6%) and expression level were significantly higher
      in ovarian cancer compared with that in benign tumor (31.8%) and in normal
      ovarian tissue (31.3%) (p<0.01), LPA(3) mRNA-positive rates and expression level
      were no significant difference in both benign tumor and normal ovarian tissue
      (p>0.05). LPA(1) mRNA expression level was significantly decreased compared with
      that of LPA(2) and LPA(3) in ovarian cancer (p<0.01); Western blotting clearly
      revealed that all ovarian cancer cell lines showed LPA(2) and LPA(3) protein. The
      positive rates and expression level of LPA(2) and LPA(3) protein were
      significantly increased in ovarian cancer (92.6%; 92.6%) compared with that in
      benign tumor (45.5%; 45.5%) and that in normal ovarian tissue (43.8%; 43.8%)
      (p<0.01); LPA(2) and LPA(3) protein-positive rates and expression level were no
      significant difference in both benign tumor and normal ovarian tissue (p>0.05).
      Correlation of clinicopathological parameters showed that LPA receptors mRNA and
      protein expression were associated with FIGO stage and histological grade, except
      pathologic types and age. The mRNA and protein expression of LPA(2) and LPA(3) in
      stages III and IV was significantly higher than that in stages I and II
      epithelial ovarian cancer (p<0.05). The mRNA and protein expression of pathologic
      grade G(3) was significantly higher compared with grade G(1) (p<0.05).
      CONCLUSION: LPA(1), LPA(2) and LPA(3) mRNA and protein expressed widely in human
      epithelial ovarian neoplasms. LPA(2) and LPA(3) may be involved in the
      development and progression of human ovarian cancer. There was a significant
      correlation between LPA(2), LPA(3) and invasion and metastasis of epithelial
      ovarian cancer. LPA(2) and LPA(3) may be a prognostic indicator in patients with
      epithelial ovarian cancer.

PMID- 17204313
TI  - Chronic mild stress inhibits BDNF protein expression and CREB activation in the
      dentate gyrus but not in the hippocampus proper.
AB  - Chronic stress is linked to development of depression and may trigger
      neurobiological changes underlying the disease. Downregulation of the secretory
      peptide brain-derived neurotrophic factor (BDNF) and the transcriptional
      regulator calcium/cyclic-AMP responsive binding protein (CREB) have been
      implicated in stress and depression-related pathology in animal studies. When
      animals are exposed to the chronic mild stress (CMS) protocol, multiple
      depression-like symptoms are observed. Here we investigated the effect of CMS on
      BDNF protein expression and CREB activation in the dentate gyrus and hippocampus
      proper. Rats exposed for 5 weeks to repeated, unpredictable, mild stressors
      showed reduced BDNF expression and inhibited phosphorylation of CREB (Ser-133) in
      the dentate gyrus (-25.0%+/-3.5% and -29.7+/-7.3%, respectively), whereas no
      significant effects were observed in the hippocampus proper. CMS-treated rats
      consumed less sucrose compared to control rats, indicating a state of anhedonia.
      Moreover, phospho-CREB levels in the dentate gyrus were positively correlated
      with the animals' sucrose intake at the end of the CMS protocol. These results
      couple chronic mild stress to a downregulation of CREB activity and BDNF protein
      expression specifically within the dentate gyrus and support the possibility that
      the BDNF-CREB system plays an important role in the response to environmental
      challenges.

PMID- 17204314
TI  - Transcription factors in allergic diseases.

PMID- 17204315
TI  - Successful sublingual immunotherapy with birch pollen has limited effects on
      concomitant food allergy to apple and the immune response to the Bet v 1 homolog
      Mal d 1.
AB  - BACKGROUND: Cross-reactivity between the major birch pollen allergen, Bet v 1,
      and the apple protein, Mal d 1, frequently causes food allergy. OBJECTIVE: To
      investigate the effects of successful sublingual immunotherapy (SLIT) with birch
      pollen extract on apple allergy and the immune response to Bet v 1 and Mal d 1.
      METHODS: Before and after 1 year of SLIT, Bet v 1-sensitized patients with oral
      allergy syndrome to apple underwent nasal challenges with birch pollen and double
      blind placebo-controlled food challenges with apple. Bet v 1-specific and Mal d 1
      specific serum antibody levels and proliferation in PBMCs and allergen-specific T
      cell lines (TCLs) were determined. Bet v 1-specific TCLs were mapped for T-cell
      epitopes. RESULTS: In 9 patients with improved nasal provocation scores to birch
      pollen, apple-induced oral allergy syndrome was not significantly reduced. Bet v
      1-specific IgE and IgG(4) levels significantly increased. Bet v 1-specific T-cell
      responses to all epitopes and those cross-reactive with Mal d 1 significantly
      decreased. However, neither Mal d 1-specific IgE and IgG(4) levels nor Mal d 1
      induced T-cell proliferation changed significantly. In contrast, Mal d 1-specific
      TCLs showed increased responses to Mal d 1 after 1 year of SLIT. CONCLUSION: This
      longitudinal study indicates that pollen SLIT does not efficiently alter the
      immune response to pollen-related food allergens, which may explain why pollen
      associated food allergy is frequently not ameliorated by pollen immunotherapy
      even if respiratory symptoms significantly improve. CLINICAL IMPLICATIONS: SLIT
      with birch pollen may have no clinical effect on associated apple allergy.

PMID- 17204316
TI  - Activation of the tissue factor pathway of blood coagulation in patients with
      chronic urticaria.
AB  - BACKGROUND: In patients with chronic urticaria (CU), plasma shows signs of
      thrombin generation and autologous plasma skin tests score positive in as many as
      95% of cases. OBJECTIVE: To evaluate the initiators of blood coagulation that
      lead to thrombin generation and fibrinolysis in CU. METHODS: Activated factor
      VII, activated factor XII, fragment F(1+2), and D-dimer plasma levels were
      measured in 37 patients with CU and 37 controls. Skin specimens from 10 patients
      with CU and 10 controls were tested for tissue factor immunohistochemically.
      RESULTS: Mean F(1+2) levels were higher in patients than controls (2.54 [SD 2.57]
      nmol/L vs 0.87 [0.26] nmol/L; P < .001); disease activity was moderate or severe
      in 9 of 11 (82%) and 9 of 26 (35%) patients showing high or normal F(1+2) levels,
      respectively (P < .025). Mean D-dimer plasma levels were higher in patients than
      controls (329 [188] ng/mL vs 236 [81] ng/mL; P < .01); disease activity was
      moderate or severe in 6 of 8 (75%) and 11 of 29 (38%) showing elevated or normal
      plasma D-dimer levels (P = NS). Factor VIIa levels were higher in patients than
      controls (2.86 ng/mL [0.66] vs 1.97 ng/mL [0.65]; P < .001). Activated factor VII
      and F(1+2) levels were correlated (r = 0.529; P = .008). Tissue factor reactivity
      was observed only in CU skin specimens. CONCLUSION: The extrinsic pathway of
      clotting cascade is activated in CU. Disease severity is associated with the
      activation of the coagulation cascade. CLINICAL IMPLICATIONS: The involvement of
      the coagulation pathway in CU opens new perspectives for a better understanding
      of the pathogenesis and, possibly, for the treatment of this disease.

PMID- 17204317
TI  - Air trapping in mild and moderate asthma: effect of inhaled corticosteroids.
AB  - BACKGROUND: Air trapping reflects small airway obstruction in asthma and can be
      assessed quantitatively by high-resolution computed tomography (HRCT).
      Hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) is deposited across all
      sizes of airways, including the small ones. However, its long-term effect on air
      trapping remains unknown in uncontrolled asthma. OBJECTIVES: To compare the
      effect of inhaled corticosteroids of different particle size - HFA-BDP and
      fluticasone propionate (FP) - on lung attenuation in mild-to-moderate
      uncontrolled asthma. METHODS: A randomized study was performed to analyze the
      effect of HFA-BDP (400 microg/d) or FP (500 microg/d) given over a period of 3
      months to patients with uncontrolled mild-to-moderate asthma. HRCT was performed
      with spirometric gating, and lung attenuation was measured at residual volume and
      at pulmonary total capacity. The difference between inspiratory and expiratory
      attenuation was calculated as an air trapping index. RESULTS: Twenty-five out of
      58 patients had abnormal air trapping and could be included in the study. Lung
      attenuation significantly diminished in the posterior zones of the lung after a 3
      month treatment with HFA-BDP or FP, but the difference between the groups was not
      significant. Adjusted mean variations of the air trapping index from baseline to
      treatment completion were 34.3 (11.2, 57.3) and 27.3 (6.4, 48.2) for the HFA-BDP
      and FP groups, respectively. However, the reduction of air trapping area was more
      pronounced in the group treated with HFA-BDP. CONCLUSION: Inhaled corticosteroids
      decrease air trapping in uncontrolled asthma regardless of their particle size.
      CLINICAL IMPLICATIONS: In mild-to-moderate asthma, air trapping assessed by HRCT
      may be a new outcome related to the control of the disease.

PMID- 17204318
TI  - Recruiting pregnant smokers into a clinical trial: using a network-model managed
      care organization versus community-based practices.
AB  - OBJECTIVES: Recruiting pregnant smokers into smoking cessation intervention
      trials is challenging. Changes in health care systems offer new opportunities to
      overcome many of the obstacles encountered by researchers attempting to address
      the significant harm from maternal smoking. Investigators could facilitate
      smoking cessation study recruitment by collaborating with health care systems
      that systematically collect patient smoking status and record it in a
      centralized, retrievable fashion. This paper reports the results of utilizing
      this novel approach and compares it with a typical decentralized practice-based
      recruitment strategy. METHODS: The study was conducted at Massachusetts General
      Hospital, in Boston, Massachusetts, from 2000 to 2005. Four hundred forty-two
      pregnant smokers were recruited for a randomized controlled trial of telephone
      delivered smoking counseling from two sources: a network-model managed care
      health plan and community-based practices (CBP). At the health plan, study
      recruitment was built on an existing system that permitted pregnant smokers to be
      identified centrally. At the CBPs, identification and referral systems had to be
      developed at each practice specifically for the study. The two strategies were
      compared on the efficiency of recruitment, characteristics of enrollees, and
      study outcome and process measures. RESULTS: The health plan strategy generated
      referrals nearly twice as fast as the CBP strategy (30.4 vs. 17.0 per month), but
      because referrals were not timely, a large proportion of women from the plan were
      too advanced in pregnancy to be eligible to enroll in the study. As a result, the
      two strategies yielded a comparable enrollment rate. Participants from the health
      plan were older, better educated, less racially diverse, more likely to be living
      with the baby's father, and less likely to have smokers in their environment.
      These differences were largely explained by the socioeconomic diversity of women
      recruited from the CBPs. Smoking cessation outcomes did not differ by recruitment
      source. CONCLUSIONS: A recruitment strategy using a health plan's centralized
      system was more efficient than a practice-based recruitment strategy at
      identifying potential study participants, but less efficient at generating study
      participants from the referrals received. Importantly, participants recruited by
      the two strategies differed by socioeconomic, but not cessation-related,
      characteristics. To date, recruiting pregnant smokers into intervention studies
      remains resource intensive and time consuming. Participant identification and
      recruitment will be greatly enhanced by health system innovations such as
      implementation of electronic medical records.

PMID- 17204319
TI  - Short glass fiber reinforced restorative composite resin with semi-inter
      penetrating polymer network matrix.
AB  - OBJECTIVES: The purpose of this study was to investigate the reinforcing effect
      of short E-glass fiber fillers on some mechanical properties of dental composite
      resin with interpenetrating polymer network (IPN)-polymer matrix. MATERIALS AND
      METHODS: Experimental composite resin was prepared by mixing short fibers (3mm in
      length) with a fraction of 22.5 wt% and IPN-resin 22.5 wt% with silane treated
      silica filler 55 wt% using high speed mixing machine. Test specimens (2 mm x 2 mm
      x 25 mm) and (9.5 mm x 5.5 mm x 3 mm) were made from the experimental composite
      (FC) and conventional particulate composite resin (control, Z250, 3M-ESPE). The
      test specimens (n=6) were either dry stored or water stored (37 degrees C for 30
      days) before the mechanical tests. Three-point bending test was carried out
      according to ISO 10477 and compression loading test was carried out using a steel
      ball (O3.0mm) with speed of 1.0mm/min until fracture. Degree of monomer
      conversion (DC%) of both composites was determined by FTIR spectrometry. Water
      sorption and solubility of specimens were also measured. Scanning electron
      microscopy was used to evaluate the microstructure of the composite. RESULTS:
      ANOVA revealed that experimental fiber composite had statistically significantly
      higher mechanical performance of flexural strength (210 MPa) and compressive load
      bearing capacity (1881 N) (p < 0.05) than control composite (111 MPa, 1031 N).
      Degree of conversion of the FC (59%) and conventional composite (57%) was at the
      same range. SIGNIFICANCE: The use of short fiber fillers with IPN-polymer matrix
      yielded improved mechanical performance compared to conventional restorative
      composite.

PMID- 17204320
TI  - Analysis of camphorquinone in composite resins as a function of shade.
AB  - OBJECTIVE: To identify and quantify the camphorquinone (CQ) used in different
      brands of composite resins as a function of the shade analyzed. MATERIALS AND
      METHODS: Filtek Z250 A3 (FZA3), Filtek Z-250 Incisal (FZI), Pyramid Enamel A1
      (PEA1), Pyramid Enamel Translucent (PET), Filtek Supreme A3E (FSA3) and Filtek
      Supreme GT (FSGT) were used. Five hundred milligrams of each resin were weighed
      and then dissolved in 1.0 ml of methanol. The samples were centrifuged to
      accelerate the sedimentation of the inorganic particles. 0.8 ml of the
      supernatant solution was collected with a pipette and assessed under gas
      chromatography coupled to the mass spectrometer (GC-MS). The results were
      compared to pure CQ solutions, used as a standard. Student's t-test, (p=0.05)
      significant at the level of 5%, compared the results of each brand shade.
      RESULTS: A smaller amount of camphorquinone was found in Filtek Z-250 (FZI) resin
      incisal shade when compared to (FZA3) A3 shade. On the other hand, Filtek Supreme
      resin featured a statistically larger camphorquinone amount in the incisal shade.
      In Pyramid Enamel resin camphorquinone was found only in shade A1, while the
      photoinitiator used in the Translucent shade was not identified. SIGNIFICANCE:
      Based on the data obtained, it is possible to conclude that a single composite
      resin brand may feature differences in amount and type of photoinitiator used.

PMID- 17204321
TI  - Anti-inflammatory function of an in situ cross-linkable conjugate hydrogel of
      hyaluronic acid and dexamethasone.
AB  - Postoperative peritoneal adhesions cause pelvic pain, infertility, and
      potentially lethal bowel obstruction. We have designed and synthesized an
      injectable hydrogel composed of cross-linkable modified hyaluronic acids (HAs)
      conjugated to dexamethasone (HAX-DEX), and investigated its anti-inflammatory
      function. HAX-DEX formed a hydrogel in <1min by cross-linking reactions between
      aldehyde groups and hydrazide groups. The hydrogel degraded in media over 5 days,
      releasing dexamethasone slowly over that time, reducing TNF-alpha and IL-6
      production from lipopolysaccharide-stimulated primary mouse macrophages in vitro.
      HAX-DEX was biocompatible on subcutaneous injection, and caused less inflammation
      than unmodified cross-linked HA.

PMID- 17204322
TI  - Calumin, a novel Ca2+-binding transmembrane protein on the endoplasmic reticulum.
AB  - We have identified a novel endoplasmic reticulum (ER)-resident protein, named
      "calumin", which is expressed in various tissues. This protein has a molecular
      mass of approximately 60 kDa and is composed of an ER-luminal domain rich in
      acidic residues, a single transmembrane segment, and a large cytoplasmic domain.
      Biochemical experiments demonstrated that the amino-terminal luminal domain is
      capable of binding Ca2+ with a high capacity and moderate affinity. In embryonic
      fibroblasts derived from calumin-knockout mice exhibiting embryonic and neonatal
      lethality, fluorometric Ca2+ imaging detected insufficient Ca2+ contents in
      intracellular stores and attenuated store-operated Ca2+ entry. Moreover, the
      mutant fibroblasts were highly sensitive to cell death induced by ER stress.
      These observations suggest that calumin plays an essential role in ER Ca2+
      handling and is also implicated in signaling from the ER, which is closely
      associated with cell-fate decision.

PMID- 17204323
TI  - Substance P stimulates late-stage rat osteoblastic bone formation through
      neurokinin-1 receptors.
AB  - Substance P (SP) is a widely distributed neuropeptide that works as a
      neurotransmitter and neuromodulator. Recently, SP receptors, particularly
      neurokinin-1 receptors (NK(1)-Rs) that have a high affinity for SP, have been
      observed not only in neuron and immune cells, but also in other peripheral cells,
      including bone cells. To identify the role of SP in bone formation, we
      investigated the expression of NK(1)-Rs in osteoblastic cells and the effects of
      SP on bone formation by rat calvarial osteoblastic cells. Rat calvarial
      osteoblastic cells were isolated and cultured for 3 weeks in alpha-MEM containing
      10% serum, ascorbic acid, dexamethasone, and beta-glycerophosphate. We then
      investigated NK(1)-R expression, SP effects on osteoblastic bone formation, and
      osteocalcin mRNA expression in osteoblastic cells. RT-PCR and immunocytochemistry
      showed that NK(1)-R mRNA was expressed and NK(1)-R was present in 14-day, but not
      7-day, cultured calvarial osteoblasts. Bone formation by cultured osteoblastic
      cells significantly increased after the addition of 10(-8)-10(-6)MSP. During 3
      weeks of culture, the addition of SP in the first week did not significantly
      increase bone formation, whereas adding SP during the first and second week or
      all 3 weeks significantly increased calvarial osteoblastic bone formation.
      Furthermore, semi-quantitative RT-PCR indicated that SP stimulated osteocalcin
      mRNA expression in the osteoblasts at day 14 or day 21, whereas SP did not
      stimulated the runX2 or type I collagen mRNA expression at day 7 but stimulated
      them at day 14. These results indicate that SP stimulates bone formation by
      osteoblastic cells via NK(1)-Rs at late-stage bone formation. These effects were
      dependent on the expression of NK(1)-R in osteoblastic cells. Our findings
      suggest that SP secreted from sensory neurons may modulate bone formation after
      the expression of SP receptors.

PMID- 17204324
TI  - Switch in X-inactivation in a JAK2 V617F-negative case of polycythemia vera with
      two acquired X-autosome translocations.
AB  - We report a JAK2 V617F-negative case of polycythemia vera with two acquired
      balanced X-autosome translocations and no history of previous exposure to
      chemo/radiotherapy. The patient's first clone carried a novel translocation
      t(X;15)(q24;q13) as a sole abnormality. The second clone exhibited an additional
      translocation, t(X;20)(q13;q13.3), which is a rare recurrent abnormality in
      myeloid malignancies. This is the first report of a hematological disorder with
      both X chromosomes being translocated. Late replication studies revealed a switch
      in X-inactivation from the X chromosome involved in t(X;15) (first clone) to the
      X chromosome involved in the t(X;20)(q13;q13.3) (second clone). The inactivation
      of the translocated X chromosomes could provide potential for the inactivation of
      the adjacent autosomal regions, resulting in epigenetic gene silencing.

PMID- 17204325
TI  - Analysis of the zinc finger domain of TnpA, a DNA targeting protein encoded by
      mobilizable transposon Tn4555.
AB  - The mobilizable transposon Tn4555, found in Bacteroides spp., is an important
      antibiotic resistance element encoding a broad spectrum beta-lactamase. Tn4555 is
      mobilized by conjugative transposons such as CTn341 which can transfer the
      transposon to a wide range of bacterial species where it integrates into
      preferred sites on the host chromosome. Selection of the preferred target sites
      is mediated by a DNA-binding protein TnpA which has a prominent zinc finger motif
      at the N-terminus of the protein. In this report the zinc finger motif was
      disrupted by site directed mutagenesis in which two cysteine residues were
      changed to serine residues. Elemental analysis indicated that the wild-type
      protein but not the mutated protein was able to coordinate zinc at a molar ration
      of 1/1. DNA binding electrophoretic mobility shift assays showed that the ability
      to bind the target site DNA was not significantly affected by the mutation but
      there was about a 50% decrease in the ability to bind single stranded DNA.
      Consistent with these results, electrophoretic mobility shift assays
      incorporating zinc chelators did not have a significant on affect the binding of
      DNA target. In vivo, the zinc finger mutation completely prevented
      transposition/integration as measured in a conjugation assay. This was in
      contrast to results in which a TnpA knockout was still able to insert into host
      genomes but there was no preferred target site selection. The phenotype of the
      zinc finger mutation was not effectively rescued by providing wild-type TnpA in
      trans. Taken together these results indicated that the zinc finger is not
      required for DNA binding activity of TnpA but that it does have an important role
      in transposition and it may mediate protein/protein interactions with integrase
      or other Tn4555 proteins to facilitate insertion into the preferred sites.

PMID- 17204326
TI  - Toxicity of three pesticides individually and in mixture to larval grass shrimp
      (Palaemonetes pugio).
AB  - This study examined the toxicity of three pesticides, singly and in mixture, to
      grass shrimp (Palaemonetes pugio) larvae. The pesticides included atrazine, an
      herbicide used on turf grass and field crops; fipronil, a persistent insecticide
      used against termites and fire ants; and imidacloprid, a systemic insecticide
      used in agricultural and home products. Fipronil was the most toxic to shrimp
      larvae with a 96-h LC50 of 0.68microg/L (95% CI 0.57-0.79microg/L). Shrimp larvae
      were less sensitive to imidacloprid with a 96-h LC50 of 308.8microg/L (95% CI
      273.6-348.6microg/L). Atrazine was non-toxic to shrimp larvae at concentrations
      up to 10,000microg/L. In mixtures, fipronil plus atrazine and imidacloprid plus
      atrazine had no change in toxicity compared to fipronil and imidacloprid tested
      singly. Similarly, a fipronil/imidacloprid mixture did not show greater than
      additive toxicity. However, when atrazine was added to the fipronil/imidacloprid
      mix, greater than additive toxicity occurred.

PMID- 17204327
TI  - Exploring central and peripheral diversity in antibody evolution.
AB  - The antigen-binding site, the paratope, of an antibody can be seen as being
      composed of a central core and a more peripheral area situated at its rim.
      Naturally these regions acquire their diversity using different mechanisms and
      they also have dissimilar roles, as they contribute differently to the binding
      interaction. Also, antigens of different size utilize these regions differently;
      while haptens mainly interact with the central core, larger antigens have
      additional interactions in more peripheral regions. Since haptens do not occupy
      the entire available paratope we hypothesized that hapten-specific antibodies, as
      they develop naturally or in the laboratory, have an imprint of the carrier
      protein they were once selected on. By using combinatorial library and phage
      display technologies on a hapten-specific antibody we were able to demonstrate
      that a peripheral carrier imprint indeed exists. We further show that such an
      imprint can act as a seed in the evolution of binders that recognize the carrier
      protein even in the absence of the hapten modification. The observed results
      provide a plausible mechanism for how haptenization of self-antigens can lead to
      the development of autoimmunity.

PMID- 17204328
TI  - Response of the rainbow trout monocyte/macrophage cell line, RTS11 to the water
      molds Achlya and Saprolegnia.
AB  - The Saprolegniales are responsible for various fish mycoses worldwide and
      considered the most important fungi afflicting fresh water fish. Saprolegniosis
      leads to massive epidermal destruction and macrophage recruitment, yet little is
      known regarding the cytological response of their piscine hosts. The objective of
      this study was to explore the response of fish macrophage to members of the
      Saprolegniales using the rainbow trout monocyte/macrophage cell line, RTS11.
      After 48 h in co-culture, RTS11 demonstrated chemotaxis, adherence and homotypic
      aggregation to both live and heat-killed fungal spores and mycelia. This
      aggregation was enhanced when using conditioned media from co-cultured RTS11 and
      Achlya, suggesting the presence of synergistic effectors of aggregation. Although
      fungal toxins were not evident, as cells remained viable throughout fungal
      overgrowth, phagocytosis was inhibited due to large fungal spore size, allowing
      these molds to evade macrophage defenses. Although class I MH and other viral
      response genes showed no significant change in expression, calreticulin and
      interleukin-8 were moderately up-regulated implicating calcium modulation and
      chemotactic response, respectively. Cyclooxygenase (COX-2) and the cytokines IL
      1beta and TNFalpha were strongly up-regulated in the presence of Achlya, while
      gene expression of the class II major histocompatibility (MH II) receptor and
      associated molecules appeared down-regulated, suggesting fungal interference of
      immune function. Previous studies have shown an increased dependence of
      macrophage in immune function at low temperatures; based upon data presented
      here, this reduction of macrophage MH II receptor expression and inability to
      phagocytose spores may limit host response thereby providing increased
      susceptibility to these opportunistic pathogens.

PMID- 17204329
TI  - A gene-environment study of the paraoxonase 1 gene and pesticides in amyotrophic
      lateral sclerosis.
AB  - Sporadic amyotrophic lateral sclerosis (SALS) causes progressive muscle weakness
      because of the loss of motor neurons. SALS has been associated with exposure to
      environmental toxins, including pesticides and chemical warfare agents, many of
      which are organophosphates. The enzyme paraoxonase 1 (PON1) detoxifies
      organophosphates and the efficacy of this enzyme varies with polymorphisms in the
      PON1 gene. To determine if an impaired ability to break down organophosphates
      underlies some cases of SALS, we compared the frequencies of PON1 polymorphisms
      in SALS patients and controls and investigated gene-environment interactions with
      self-reported pesticide/herbicide exposure. The PON1 coding polymorphisms L55M,
      Q192R and I102V, and the promoter polymorphisms -909c>g, -832g>a, -162g>a and 
      108c>t, were genotyped in 143 SALS patients and 143 matched controls. Statistical
      comparisons were carried out at allele, genotype and haplotype levels. The PON1
      promoter allele -108t, which reduces PON1 expression, was strongly associated
      with SALS. Overall, promoter haplotypes that decrease PON1 expression were
      associated with SALS, whereas haplotypes that increase expression were associated
      with controls. Coding polymorphisms did not correlate with SALS. Gene-environment
      interactions were identified at the allele level for some promoter SNPs and
      pesticide/herbicide exposure, but not at the genotype or haplotype level. In
      conclusion, some PON1 promoter polymorphisms may predispose to SALS, possibly by
      making motor neurons more susceptible to organophosphate-containing toxins.

PMID- 17204330
TI  - The two modes of binding of Ru(phen)(2)dppz(2+) to DNA: thermodynamic evidence
      and kinetic studies.
AB  - The binding of Ru(phen)(2)dppz(2+) (dppz=dipyrido[3,2-a:2',3'-c]phenazine) to DNA
      was investigated at pH 7.0 and 25 degrees C using stopped-flow and
      spectrophotometric methods. Equilibrium measurements show that two modes of
      binding, whose characteristics depend on the polymer to dye ratio (C(P)/C(D)),
      are operative. The binding mode occurring for values of C(P)/C(D) higher than 3
      exhibits positive cooperativity, which is confirmed by kinetic experiments. The
      reaction parameters are K=2 x 10(3)M(-1), omega=550, n=1, k(r)=(1.9+/-0.5) x
      10(7)M(-1)s(-1) and k(d)=(9.5+/-2.5)x10(3)s(-1) at I=0.012 M. The results are
      discussed in terms of prevailing surface interaction with DNA grooves accompanied
      by partial intercalation of the dppz residue. The other binding mode becomes
      operative for C(P)/C(D)<3 and the equilibria analysis shows this is an ordinary
      intercalation mode (K=1.3 x 10(6) M(-1), n=1.5 at I=0.012 M and K=2 x 10(5) M(
      1), n=1.2 at I=0.21 M). Similar behaviour is displayed by double-stranded
      poly(A).

PMID- 17204331
TI  - Observation of terahertz vibrations in Pyrococcus furiosus rubredoxin via
      impulsive coherent vibrational spectroscopy and nuclear resonance vibrational
      spectroscopy--interpretation by molecular mechanics.
AB  - We have used impulsive coherent vibrational spectroscopy (ICVS) to study the Fe(S
      Cys)(4) site in oxidized rubredoxin (Rd) from Pyrococcus furiosus (Pf). In this
      experiment, a 15 fs visible laser pulse is used to coherently pump the sample to
      an excited electronic state, and a second <10 fs pulse is used to probe the
      change in transmission as a function of the time delay. PfRd was observed to
      relax to the ground state by a single exponential decay with time constants of
      approximately 255-275 fs. Superimposed on this relaxation are oscillations caused
      by coherent excitation of vibrational modes in both excited and ground electronic
      states. Fourier transformation reveals the frequencies of these modes. The
      strongest ICV mode with 570 nm excitation is the symmetric Fe-S stretching mode
      near 310 cm(-1), compared to 313 cm(-1) in the low temperature resonance Raman.
      If the rubredoxin is pumped at 520 nm, a set of strong bands occurs between 20
      and 110 cm(-1). Finally, there is a mode at approximately 500 cm(-1) which is
      similar to features near 508 cm(-1) in blue Cu proteins that have been attributed
      to excited state vibrations. Normal mode analysis using 488 protein atoms and 558
      waters gave calculated spectra that are in good agreement with previous nuclear
      resonance vibrational spectra (NRVS) results. The lowest frequency normal modes
      are identified as collective motions of the entire protein or large segments of
      polypeptide. Motion in these modes may affect the polar environment of the redox
      site and thus tune the electron transfer functions in rubredoxins.

PMID- 17204332
TI  - Transformation of arbitrary distributions to the normal distribution with
      application to EEG test-retest reliability.
AB  - Many variables in the social, physical, and biosciences, including neuroscience,
      are non-normally distributed. To improve the statistical properties of such data,
      or to allow parametric testing, logarithmic or logit transformations are often
      used. Box-Cox transformations or ad hoc methods are sometimes used for parameters
      for which no transformation is known to approximate normality. However, these
      methods do not always give good agreement with the Gaussian. A transformation is
      discussed that maps probability distributions as closely as possible to the
      normal distribution, with exact agreement for continuous distributions. To
      illustrate, the transformation is applied to a theoretical distribution, and to
      quantitative electroencephalographic (qEEG) measures from repeat recordings of 32
      subjects which are highly non-normal. Agreement with the Gaussian was better than
      using logarithmic, logit, or Box-Cox transformations. Since normal data have
      previously been shown to have better test-retest reliability than non-normal data
      under fairly general circumstances, the implications of our transformation for
      the test-retest reliability of parameters were investigated. Reliability was
      shown to improve with the transformation, where the improvement was comparable to
      that using Box-Cox. An advantage of the general transformation is that it does
      not require laborious optimization over a range of parameters or a case-specific
      choice of form.

PMID- 17204333
TI  - A spontaneously immortalized Schwann cell line to study the molecular aspects of
      metachromatic leukodystrophy.
AB  - The arylsulfatase A (ASA)-deficient mouse is a murine model of human
      metachromatic leukodystrophy (MLD) caused by a genetic defect in the ASA gene.
      Deficiency of ASA causes accumulation of cerebroside-3-sulfate (sulfatide) in
      visceral organs and in the central and peripheral nervous system, which
      subsequently causes demyelination in these areas. To investigate further the
      cellular pathomechanism of MLD, we established spontaneously immortalized Schwann
      cell lines from ASA-deficient mice. Cells showed marked sulfatide storage in the
      late endosomal/lysosomal compartment. This sulfatide accumulation can be further
      increased by external treatment with sulfatide using a lipid based transfection
      reagent as a cargo. The accumulated sulfatide was degraded in response to ASA
      treatment and first examination revealed that alteration on the molecular level
      found in ASA-deficient mice can also be observed in the presented cell culture
      model. Hence, these cells could be a suitable model to study MLD at a molecular
      level.

PMID- 17204334
TI  - A new approach to assess function after sciatic nerve lesion in the mouse -
      adaptation of the sciatic static index.
AB  - Among the numerous ways of assessing regeneration after peripheral nerve lesions,
      the analysis of gait is one of the most important, because it shows the recovery
      of function, which is the ultimate goal of the repair machinery. The sciatic
      function index was introduced as a method to assess reinnervation after an
      experimental sciatic nerve lesion, and was adapted to the mouse model. The
      sciatic static index (SSI), is more simple and practical to perform, and is not
      so influenced by gait's velocity, but this method has not yet been adapted to the
      mouse model of sciatic lesion. We used 63 male Swiss mice (Mus musculus) to
      develop a formula to the sciatic static index in mice (SSIm). The animals were
      divided on three groups (control, transection and crush). They were evaluated at
      the preoperative and 7th, 14th, 21st, 28th, 35th and 42nd days postoperative by
      the ink track method (SFI), and by the acquisition of photographs of the plantar
      aspects of the injured and uninjured hind paws. The parameters evaluated were the
      1-5 toe spread (TS), the 2-4 toe spread (ITS) and the distance between the tip of
      the third toe and the most posterior aspect of the paw (PL), on both methods.
      After verifying the temporal pattern of function, correlation and reproducibility
      of the measurements, we performed a multiple regression analysis using SFI values
      as dependent variable, and the TS, ITS and PL measured with the photo method as
      independent variables, and found the formula of the SSI for mice (SSIm). The
      three groups (control, transection and crush) had a characteristic pattern of
      dysfunction. The parameters measured in the ink and photo method had variable but
      significant correlations between them (P<0.000), but photo method of measurement
      showed a better reproducibility. The correlation between SFI and SSIm showed a
      high correlation coefficient (r=0.892, P<0.000), and demonstrates that SSIm can
      be used as an alternative method to assess the functional status relative of
      sciatic nerve activity in mice.

PMID- 17204335
TI  - ERPWAVELAB a toolbox for multi-channel analysis of time-frequency transformed
      event related potentials.
AB  - The open source toolbox 'ERPWAVELAB' is developed for multi-channel time
      frequency analysis of event related activity of EEG and MEG data. The toolbox
      provides tools for data analysis and visualization of the most commonly used
      measures of time-frequency transformed event related data as well as data
      decomposition through non-negative matrix and multi-way (tensor) factorization.
      The decompositions provided can accommodate additional dimensions like subjects,
      conditions or repeats and as such they are perfected for group analysis.
      Furthermore, the toolbox enables tracking of phase locked activity from one
      channel-time-frequency instance to another as well as tools for artifact
      rejection in the time-frequency domain. Several other features are highlighted.
      ERPWAVELAB can freely be downloaded from www.erpwavelab.org, requires EEGLAB
      [Delorme A, Makeig S. EEGLAB: an open source toolbox for analysis of single-trial
      EEG dynamics including independent component analysis. J Neurosci Meth 2004;134:9
      21] and runs under MATLAB (The Mathworks, Inc.).

PMID- 17204336
TI  - Reversible and irreversible knockout of the ventroposterolateral thalamic nucleus
      measured by intracerebral SEP recordings in the rat brain--an aid to
      neuronavigation in small nuclei.
AB  - Centrally active drugs are often hard to administer because of the blood brain
      barrier, and frequently high systemic doses are required to reach sufficient
      brain parenchyma concentrations, since these drugs are, additionally, diluted in
      the total blood volume. Moreover, topical administration via the systemic route
      is not possible. We here propose a technique for the local, quantitative
      deposition of active substances at defined intracerebral targets, e.g. the
      thalamic nuclei. We used a long micropipette and stereotactically advanced it to
      the desired coordinates under electrophysiological control. The pipette acted as
      both an electrode for intracerebral recordings and as a transportation means for
      the drug. The amplitude of intracerebral evoked potentials relayed by the
      thalamic nucleus to the sensorimotor cortex indicated the distance between the
      pipette tip and the neurons of the targeted nucleus. Data were obtained from
      anesthetized rats, where the micropipette was advanced towards the nucleus
      ventralis posterolateralis (VPL) during contralateral electrical forepaw
      stimulation and intracerebral recording of somatosensory evoked potentials.
      Within the VPL we either injected lidocaine or kainic acid, both resulting in an
      attenuation of the intracerebral as well as the cortical evoked potentials. This
      proposed tool may be useful for functional investigations of deep brain
      structures.

PMID- 17204337
TI  - Etiology of vertigo in children.
AB  - OBJECTIVE: To detect the most common causes of vertigo in children. METHODS:
      Fifty-four children (20 boys and 34 girls) aged 3-16 years, who presented with
      vertigo attacks during a 3-year period, were studied. A detailed medical history
      for vestibular symptoms and migraine was obtained from our patients or their
      parents. All patients underwent otolaryngologic, ophthalmologic and neurologic
      clinical evaluation. A detailed laboratory examination, including serologic tests
      for viral infections, was also obtained. Additionally, a complete audiological
      and neurotologic evaluation was performed. Computed tomography (CT) scans and
      magnetic resonance imaging (MRI) were obtained in selected cases. RESULTS: Viral
      infections, benign paroxysmal vertigo of childhood and migraine were the most
      common causes of vertigo accounting for approximately 65% of our patients. Otitis
      media, head trauma, benign paroxysmal positional vertigo, Meniere's disease and
      brain tumor were less common causes of vertigo. CONCLUSIONS: A peripheral type of
      vertigo was found in most cases. Diagnostic approach in vertigo in children
      should include a detailed history and clinical examination in conjunction with a
      test battery of audiological and neurotologic tests. When a central cause of
      vertigo is suspected an MRI or CT scan should be ordered.

PMID- 17204339
TI  - A novel high throughput quantum dot-based fluorescence assay for quantitation of
      virus binding and attachment.
AB  - Quantum dots (QDots) are fluorescent semiconductor nanocrystals with a narrow
      emission spectrum, high quantum yield, and excellent photostability. These unique
      properties of QDots have been utilized to develop a fluorescent binding assay
      using biotinylated human T cell leukemia virus type 1 (biot-HTLV-1) conjugated
      with streptavidin-coated QDots that enabled both qualitative and quantitative
      analyses of viral binding. The specificity and linearity of the assay was
      demonstrated utilizing T cells, the primary HTLV-1-susceptible cell population.
      Furthermore, differential binding of HTLV-1 was analyzed in additional cell types
      of clinical relevance including primary CD4(+) and CD8(+) T cells, dendritic
      cells (DCs), monocytes, bone marrow progenitor cells, and epithelial cells. DCs
      exhibited maximum binding affinity when compared to other examined cell types
      except the Jurkat and SUP-T1 T cell lines. Finally, blocking antibodies directed
      against a putative HTLV-1 receptor on DCs; DC-SIGN (dendritic cell-specific ICAM
      3-grabbing non-integrin), were utilized to study the inhibition of HTLV-1 binding
      to target cells. Overall, these results demonstrated that this novel high
      throughput assay can be utilized to study the binding of a biotinylated virus and
      has implications for screening of viral binding inhibitors as well as host
      membrane proteins that may serve as receptors for viral entry.

PMID- 17204340
TI  - Simultaneous assessment of autonomic function and anxiety-related behavior in
      BALB/c and C57BL/6 mice.
AB  - In humans, anxiety is accompanied by changes in autonomic nervous system
      function, including increased heart rate, body temperature, and blood pressure,
      and decreased heart rate variability. In rodents, anxiety is inferred by
      examining anxiety-related behavioral responses such as avoidance and freezing,
      and more infrequently by assessing autonomic responses to anxiogenic stimuli.
      However, few studies have simultaneously measured behavioral and autonomic
      responses to aversive stimuli in rodents and it remains unclear whether autonomic
      measures are reliable correlates of anxiety-related behavior in these animal
      models. Here we recorded for the first time heart rate and body temperature in
      freely moving BALB/c and C57BL/6 mice during exposure to an unfamiliar
      environment. Our data show that upon exposure to a novel open field, BALB/c mice
      showed increased anxiety-related behavior, reduced heart rate and higher heart
      rate variability (HRV) when compared with C57BL/6 mice. Regression analysis
      revealed a significant correlation between both heart rate and long-term HRV
      measures and locomotor activity and time spent in the center of the open field,
      but no correlation between body temperature and any behavioral variables. In the
      free exploration test, in which animals were allowed direct access to a novel
      environment from a familiar environment without experimenter handling,
      significant correlations were found only between heart rate and total locomotor
      activity, but not time spent in the unfamiliar chamber despite increased anxiety
      related behavior in BALB/c mice. These findings demonstrate that increased
      anxiety-related behavior in BALB/c mice is not associated with specific changes
      in heart rate, HRV, or body temperature.

PMID- 17204341
TI  - Protein phosphatase 2A plays a crucial role in Giardia lamblia differentiation.
AB  - The ability of Giardia lamblia to undergo two distinct differentiations in
      response to physiologic stimuli is central to its pathogenesis. The giardial
      cytoskeleton changes drastically during encystation and excystation. However, the
      signal transduction pathways mediating these transformations are poorly
      understood. We tested the hypothesis that PP2A, a highly conserved
      serine/threonine protein phosphatase, might be important in giardial
      differentiation. We found that in vegetatively growing trophozoites, gPP2A-C
      protein localizes to basal bodies/centrosomes, and to cytoskeletal structures
      unique to Giardia: the ventral disk, and the dense rods of the anterior,
      posterior-lateral, and caudal flagella. During encystation, gPP2A-C protein
      disappears from only the anterior flagellar dense rods. During excystation, gPP2A
      C localizes to the cyst wall in excysting cysts but is not found in the wall of
      cysts with emerging excyzoites. Transcriptome and immunoblot analyses indicated
      that gPP2A-C mRNA and protein are upregulated in mature cysts and during the
      early stage of excystation that models passage through the host stomach. Stable
      expression of gPP2A-C antisense RNA did not affect vegetative growth, but
      strongly inhibited the formation of encystation secretory vesicles (ESV) and
      water-resistant cysts. Moreover, the few cysts that formed were highly defective
      in excystation. Thus, gPP2A-C localizes to universal cytoskeletal structures and
      to structures unique to Giardia. It is also important for encystation and
      excystation, crucial giardial transformations that entail entry into and exit
      from dormancy.

PMID- 17204344
TI  - A functional modulation for timing a movement: a coordinative structure in
      baseball hitting.
AB  - In baseball hitting, a powerful bat-swing needs to be produced by utilizing
      ground reaction force (GRF) and it should also be temporally coordinated relative
      to the flight of the pitch. The temporal organization of hitting movements
      associated with these task requirements was investigated by analyzing GRF during
      hitting slow and fast pitches. The timing of stepping with a front foot and
      shifting weight forward was modulated relative to the pitch's speed. The temporal
      relation between successive motion phases was compensatory and timing variability
      progressively reduced up to ball-bat contact. These results demonstrated the
      coordinative structure of the hitting movement for timing the bat-swing relative
      to the pitch's flight.

PMID- 17204345
TI  - Synthesis of PHBV block copolymers driven by an oscillatory genetic network.
AB  - Artificial genetic networks constitute a powerful tool to achieve various
      biotechnological objectives. In this work, we propose the modification of an
      oscillatory genetic network, known as the repressilator, to drive synthesis of
      poly(3hydroxybutyrate-co-3hydroxyvalerate) (PHBV) block copolymer chains in
      recombinant Escherichia coli cells. To study the feasibility of this idea, we
      developed a detailed mathematical model describing the dynamics of the genetic
      network, which drive the formation of monomer units that are subsequently
      incorporated into actively growing block copolymer chains. Extensive simulation
      studies have shown that appropriate choice of the molecular characteristics of
      the network and manipulation of extracelllular conditions lead to tight control
      of both the micro- and macro-structures of the resulting block copolymer chains.
      Thus, the model can guide network design aiming at producing block copolymer
      structures with desirable characteristics.

PMID- 17204346
TI  - Unit-length, single-stranded circular DNAs of both polarity of begomoviruses are
      generated in Escherichia coli harboring phage M13-cloned begomovirus genome with
      single copy of replication origin.
AB  - Replication of genomic DNAs of plant-pathogenic begomoviruses has been
      demonstrated in prokaryotes, which supported the possibility of analyzing DNA
      replication process of begomoviruses in bacteria. However, previous studies
      indicated that the replication of begomovirus DNAs in prokaryotes requires tandem
      constructs of viral genomes with at least two copies of the origin of replication
      (ori). In this study, phage M13 vector harboring the unit-length genome with only
      a single copy of ori of a mono-partite begomovirus, Ageratum yellow vein virus PD
      isolate (AYVV-[PD]), was constructed and used to investigate the replication of
      AYVV-[PD] DNAs in Escherichia coli. The generation of single-stranded, circular
      DNAs (sscDNAs) corresponding to the unit-length AYVV-[PD] genome of both polarity
      was observed and verified. Replication-associated (Rep) protein of AYVV-[PD] was
      detected only in bacteria generating the corresponding sscDNAs, whereas
      disruption of the Rep gene abolished the phenomenon. The results suggested that a
      single copy of ori is sufficient for the prokaryotes to support the generation of
      unit-length, genomic sscDNAs of begomoviruses, which requires the presence of
      functional Rep protein.

PMID- 17204347
TI  - Does providing cost-effectiveness information change coverage priorities for
      citizens acting as social decision makers?
AB  - Escalating costs have generated increasing calls for Medicare to use cost
      effectiveness as one criterion in determining coverage decisions. Decision-makers
      in U.S. health care have largely assumed that the public will reject any explicit
      consideration of cost in coverage policy, but there has been little formal
      testing of that hypothesis. We tested this assumption in a pilot study in which
      groups of citizens learned about and discussed health care costs, CEA methods,
      and common ethical issues embedded in CEA. Participants received information
      about 14 conditions and treatments and were asked to prioritize them for funding
      by Medicare under assumptions of constrained resources. Contrary to prevailing
      assumptions, this diverse sample understood CEA, were largely open to its use,
      and changed their own funding priorities when given cost-effectiveness ratio
      information.

PMID- 17204348
TI  - Reorienting Health Ministry roles in transition settings: capacity and strategy
      gaps.
AB  - Health authorities in developing countries must often cope with rapid changes in
      the administrative, policy and socioeconomic contexts in which they work. Changes
      in this external environment have important implications for the roles that
      health planners can effectively play and the leverage they exercise throughout
      the system. This paper examines the challenges associated with reorienting
      ministry roles from administrative fiat to overall orchestration and strategic
      steering, using health workforce management in transitional Vietnam as a
      backdrop. Decentralization, commercialization of services and rising inequalities
      have reduced the efficacy of the administrative controls and standardized
      strategy on which Vietnam's Ministry of Health has traditionally relied.
      Reorientation, in Vietnam and elsewhere, depends on bridging significant capacity
      and strategy gaps, notably in the strengthening of information, planning and
      accountability systems that respect both the limitations of central control and
      the diversity of local conditions.

PMID- 17204342
TI  - Analysis of the Leishmania donovani transcriptome reveals an ordered progression
      of transient and permanent changes in gene expression during differentiation.
AB  - Leishmania donovani is an intracellular protozoan parasite that causes kala-azar
      in humans. During infection the extracellular insect forms (promastigotes)
      undergo rapid differentiation to intracellular amastigotes that proliferates in
      phagolysosomes of mammalian macrophages. We used microarray-based expression
      profiling to investigate the time-course of changes in RNA abundance during
      promastigote-to-amastigote differentiation in a host-free system that mimics this
      process. These studies revealed that several hundred genes underwent an ordered
      progression of transient or permanent up- and down-regulation during
      differentiation. Genes that were permanently up-regulated in amastigotes were
      enriched for transporters and surface proteins, but under-represented in genes
      involved in protein and other metabolism. Most of these changes occurred late in
      the differentiation process, when morphological differentiation was essentially
      complete. Down-regulated genes were over-represented in those involved in cell
      motility, growth and/or maintenance, and these changes generally occurred earlier
      in the process. Genes that were transiently up- or down-regulated during
      differentiation included those encoding heat shock proteins, ubiquitin
      hydrolases, RNA binding proteins, protein kinases, a protein phosphatase, and a
      histone deacetylase. These results suggest that changes in mRNA abundance may be
      important in signal transduction, as well as protein and mRNA turnover, during
      differentiation. In addition to these mRNA changes, other transcripts including
      one or more rRNAs and snoRNAs, and non-coding RNAs from several telomeres, also
      showed substantial changes in abundance during the differentiation process. This
      paper provides the first genome-scale quantitative analysis of gene expression
      during the transition from promastigotes to amastigotes and demonstrates the
      utility of the host-free differentiation system.

PMID- 17204349
TI  - Neuropeptide Y (NPY) Y2 receptor-selective agonist inhibits food intake and
      promotes fat metabolism in mice: combined anorectic effects of Y2 and Y4 receptor
      selective agonists.
AB  - Peripheral administration of the endogenous Y(2) and Y(4) receptor selective
      agonists, PYY(3-36) and PP, have been shown to inhibit food intake and body
      weight gain in rodents, and to reduce appetite and caloric intake in humans. We
      have previously developed a long-acting, potent and highly selective Y(2)
      receptor selective agonist, N-alpha-Ac-[Nle(24,28), Trp(30), Nva(31), Psi(35
      36)]PYY(22-36)-NH(2) (BT-48). BT-48 (ip) dose-dependently inhibited ad lib food
      intake and also decreased the respiratory quotient in mice during both the light
      and dark periods. The latter observation is indicative of enhanced fat
      metabolism. Moreover, BT-48 also inhibited food intake in fasted mice. Combined
      ip administration of BT-48 (50nmol/mouse) with a highly potent and selective Y(4)
      anorectic peptide, BVD-74D (50nmol/mouse), resulted in a powerful and long
      lasting inhibitory effect on food intake. As expected, this inhibitory effect on
      food intake was nearly double that exhibited by either peptide (50nmol/mouse)
      alone. In summary, BT-48, unlike PYY(3-36), exhibits little or no affinity to
      other "Y" receptors, and may therefore have a better clinical potential than
      PYY(3-36) for control of food intake. Moreover, it appears that treatment with a
      combination of Y(2) and Y(4) receptor selective agonists may constitute a more
      powerful approach to control food intake than treatment with either of these
      agonists alone.

PMID- 17204350
TI  - Neuropeptide Y in the recurrent mossy fiber pathway.
AB  - In the epileptic brain, hippocampal dentate granule cells become synaptically
      interconnected through the sprouting of mossy fibers. This new circuitry is
      expected to facilitate epileptiform discharge. Prolonged seizures induce the long
      lasting neoexpression of neuropeptide Y (NPY) in mossy fibers. NPY is released
      spontaneously from recurrent mossy fiber terminals, reduces glutamate release
      from those terminals by activating presynaptic Y2 receptors, and depresses
      granule cell epileptiform activity dependent on the recurrent pathway. These
      effects are much greater in rats than in C57BL/6 mice, despite apparently
      equivalent mossy fiber sprouting and neoexpression of NPY. This species
      difference can be explained by contrasting changes in the expression of mossy
      fiber Y2 receptors; seizures upregulate Y2 receptors in rats but downregulate
      them in mice. The recurrent mossy fiber pathway may synchronize granule cell
      discharge more effectively in humans and mice than in rats, due to its lower
      expression of either NPY (humans) or Y2 receptors (mice).

PMID- 17204351
TI  - Central infusion of the melanocortin receptor antagonist agouti-related peptide
      (AgRP(83-132)) prevents cachexia-related symptoms induced by radiation and colon
      26 tumors in mice.
AB  - Cachexia is a clinical wasting syndrome that occurs in multiple disease states,
      and is associated with anorexia and a progressive loss of body fat and lean mass.
      The development of new therapeutics for this disorder is needed due to poor
      efficacy and multiple side effects of current therapies. The pivotal role played
      by the central melanocortin system in regulating body weight has made this an
      attractive target for novel cachexia therapies. The mixed melanocortin receptor
      antagonist AgRP is an endogenous peptide that induces hyperphagia. Here, we used
      AgRP(83-132) to investigate the ability of melanocortin antagonism to protect
      against clinical features of cachexia in two distinct animal models. In an acute
      model, food intake and body weight gain were reduced in mice exposed to radiation
      (300 RAD), and delivery of AgRP(83-132) into the lateral cerebral ventricle
      prevented these effects. In a chronic tumor cachexia model, adult mice were
      injected subcutaneously with a cell line derived from murine colon-26
      adenocarcinoma. Typical of cachexia, tumor-bearing mice progressively reduced
      body weight and food intake, and gained significantly less muscle mass than
      controls. Administration of AgRP(83-132) into the lateral ventricles
      significantly increased body weight and food intake, and changes in muscle mass
      were similar to the tumor-free control mice. These findings support the idea that
      antagonism of the central melanocortin system can reduce the negative impact of
      cachexia and radiation therapy.

PMID- 17204352
TI  - Role of neuropeptide Y and its receptors in the progression of endocrine-related
      cancer.
AB  - The neuropeptide Y (NPY) family of peptides, in addition to its many
      physiological actions, has also been involved in the modulation of tumor
      progression, with specific reference to endocrine-related cancers such as
      neuroendocrine tumors, breast and prostate cancers. These have been found either
      to express NPY receptors, or to secrete NPY-related peptides, or both. The study
      of the role of the NPY family of peptides in the biology of endocrine-related
      tumors, specifically concerning cell proliferation, angiogenesis, invasion and
      metastatization, may help to clarify some aspects of tumor pathophysiology, as
      well as to indicate novel diagnostic markers and therapeutical approaches.

PMID- 17204353
TI  - Serum activity of dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) in breast-fed
      infants with symptoms of allergy.
AB  - Beta-casomorphins, opioid peptides present in mother's milk, are a good substrate
      for DPPIV (EC 3.4.14.5) which is a major factor limiting the half-life of
      biologically active peptides. Serum DPPIV activity of two groups of infants
      (healthy and atopic dermatitis) and contents of beta-casomorphin-5 and -7 in
      their mothers' milk were determined in the study. We have found correlation
      between those two parameters in the group of children with atopic dermatitis
      syndromes, while no such a correlation was found in the control group.

PMID- 17204354
TI  - Simulation of progressive spinal deformities in Duchenne muscular dystrophy using
      a biomechanical model integrating muscles and vertebral growth modulation.
AB  - BACKGROUND: Ninety percent of Duchenne muscular dystrophy patients develop
      scoliosis in parallel with evident muscular and structural impairment. Altered
      muscular spinal loads acting on growing vertebrae are likely to promote a self
      sustaining spinal deformation process. The purpose of this study was to simulate
      the effect of asymmetrical fat infiltration of the erector spinae muscles
      combined with vertebral growth modulation over a period of growth spurt. METHODS:
      A finite element model of the trunk was built. It integrates (1) longitudinal
      growth of vertebral bodies and its modulation due to mechanical stresses, (2)
      muscles and control processes generating muscle recruitment and forces. Three
      different impairments of the erector spinae muscles were considered and their
      actions over 12 consecutive cycles representing a span of 12 months were
      analyzed. FINDINGS: When asymmetrical muscle degeneration was simulated and
      weaker erector spinae muscles were located on the convex side of the curve, mild
      scoliosis (Cobb angle of 8-19 degrees ) was induced in the frontal plane and the
      kyphosis increased from 72 degrees to 110 degrees in all simulations. Those
      changes were accompanied by a substantial increase of muscle activity in the
      Rectus Abdominus and Obliquus Internus. INTERPRETATION: Scoliosis as documented
      in the literature were induced through an asymmetrical activity in the erector
      spinae muscles and it can be hypothesized that the Rectus Abdominus and Obliquus
      Internus have a role in maintaining balance and counteracting against spine
      torsion. This study demonstrated the feasibility of the modeling approach to
      investigate a musculo-skeletal deformation process based on a neuromuscular
      deficit.

PMID- 17204355
TI  - Application of a calibration method provides more realistic results for a finite
      element model of a lumbar spinal segment.
AB  - BACKGROUND: An important step in finite element modeling is the process of
      validation to derive clinical relevant data. It can be assumed that defect states
      of a finite element model, which have not been validated before, may predict
      wrong results. The purpose of this study was to show the differences in accuracy
      between a calibrated and a non-calibrated finite element model of a lumbar spinal
      segment for different clinical defects. METHODS: For this study, two
      geometrically identical finite element models were used. An in vitro experiment
      was designed, deriving data for the calibration. Frequently used material
      properties were obtained from the literature and transferred into the non
      calibrated model. Both models were validated on three clinical defects: bilateral
      hemifacetectomy, nucleotomy and interspinous defects, whereas in vitro range of
      motion data served as control points. Predictability and accuracy of the
      calibrated and non-calibrated finite element model were evaluated and compared.
      FINDINGS: Both finite element models could mimic the intact situation with a good
      agreement. In the defects, the calibrated model predicted motion behavior with
      excellent agreement, whereas the non-calibrated model diverged greatly.
      INTERPRETATION: Investigating the biomechanical performance of implants and load
      distribution of different spinal structures by numerical analysis requires not
      only good agreement with the intact segment, but also with the defect states,
      which are initiated prior to implant insertion. Because of more realistic results
      the calibration method may be recommended, however, it is more time consuming.

PMID- 17204356
TI  - Post Launch Monitoring of food products: what can be learned from
      pharmacovigilance.
AB  - Post Launch Monitoring (PLM) is one of the new approaches that are used in
      assessing the safety of novel foods or ingredients. It shares a close resemblance
      with procedures applied in the field of medicines, where Post Marketing
      Surveillance (PMS) has been carried out since the beginning of the 1960s. For
      this reason, Unilever and the Netherlands Pharmacovigilance Centre Lareb,
      maintaining the national reporting scheme in the Netherlands for adverse drug
      reactions, have been working together to optimize the Unilever's Post Launch
      Monitoring service. As a result of this cooperation a practical model for
      conducting PLM for food products has been developed. This model is also
      applicable for consumer products in general. The system allows for coding and
      assessing reports and the early detection of 'signals' of unintended health
      reactions. The methodological issues surrounding reporting of possible health
      reactions and practical issues surrounding coding and assessment of the reports
      that were encountered in the first period of this partnership are discussed. In
      addition, similarities and differences concerning PMS and PLM are described.

PMID- 17204357
TI  - Tuning the engine of cognition: a focus on NMDA/D1 receptor interactions in
      prefrontal cortex.
AB  - The prefrontal cortex of the primate frontal lobes provides the capacity for
      judgment which can constantly adapt behavior in order to optimize its outcome.
      Adjudicating between long-term memory programs and prepotent responses, this
      capacity reviews all incoming information and provides an interpretation
      dependent on the events that have just occurred, the events that are predicted to
      happen, and the alternative response strategies that are available in the given
      situation. It has been theorized that this function requires two essential
      integrated components, a central executive which guides selective attention based
      on mechanisms of associative memory, as well as the second component, working
      memory buffers, in which information is held online, abstracted, and translated
      on a mental sketchpad of work in progress. In this review, we critically outline
      the evidence that the integration of these processes and, in particular, the
      induction and maintenance of persistent activity in prefrontal cortex and related
      networks, is dependent upon the interaction of dopamine D1 and glutamate NMDA
      receptor signaling at critical nodes within local circuits and distributed
      networks. We argue that this interaction is not only essential for
      representational memory, but also core to mechanisms of neuroadaptation and
      learning. Understanding its functional significance promises to reveal major new
      insights into prefrontal dysfunction in schizophrenia and, hence, to target a new
      generation of drugs designed to ameliorate the debilitating working memory
      deficits in this disorder.

PMID- 17204358
TI  - Isobolographic characterization of interactions between vigabatrin and tiagabine
      in two experimental models of epilepsy.
AB  - To characterize the type of interactions between vigabatrin (VGB) and tiagabine
      (TGB) -- two newer antiepileptic drugs influencing GABA-ergic neurotransmitter
      system, the isobolographic analysis was used in two experimental models of
      epilepsy: the maximal electroshock seizure threshold (MEST) test and
      pentylenetetrazole (PTZ)-induced seizures in mice. Results indicated that VGB and
      TGB administered separately (i.p.) increased the electroconvulsive threshold in
      mice, which allowed the calculation of their TID(20) values (threshold increasing
      doses by 20% over the threshold of control animals) in the MEST test. The TID(20)
      for VGB was 226.2 mg/kg and that for TGB was 4.4 mg/kg. With isobolography, the
      combinations of VGB with TGB (at fixed-ratios of 1:3, 1:1 and 3:1) exerted
      additive interactions in the MEST test in mice. Similarly, VGB and TGB injected
      separately (i.p.) suppressed the PTZ-induced seizures, and their ED(50) values
      (median effective doses, protecting 50% of the animals tested against clonic
      convulsions) for VGB and TGB were 622.5 mg/kg and 0.8 mg/kg, respectively.
      Isobolographic analysis of interactions revealed that the combinations of VGB
      with TGB at the fixed-ratios of 1:3 and 1:1 produced supra-additive (synergistic)
      interactions against PTZ-induced seizures. Only the combination of VGB with TGB
      at the fixed-ratio of 3:1 was additive in the PTZ test. The evaluation of acute
      adverse-effect potential for all fixed-ratio combinations of VGB with TGB
      (administered at their TID(20) and ED(50) values from the MEST and PTZ tests)
      revealed that none of the examined combinations affected motor coordination in
      the chimney test and altered neuromuscular tone in the grip-strength test in
      mice. In contrast, VGB in combinations with TGB produced the antinociceptive
      effects with respect to suppression of acute thermal pain in animals subjected to
      the hot-plate test. Based on this preclinical study, one can ascertain that the
      combination of VGB with TGB would provide an adequate seizure control in
      epileptic patients.

PMID- 17204359
TI  - Sex differences in cardiac vagal control in a depressed sample: implications for
      differential cardiovascular mortality.
AB  - Previous studies suggest depression is a risk factor for all cause mortality,
      with depressed men at greater risk than depressed women. Diminished cardiac vagal
      control (CVC) in depressed patients has also been found to increase risk of
      cardiac mortality. Previous research found that depressed women have higher CVC
      than depressed men suggesting CVC might be related to the discrepancy in
      mortality rates between depressed men and women. This finding, however, was in
      the context of a study with several methodological weaknesses. The current study
      sought to replicate the sex difference in CVC in a sample of 137 medically
      healthy and clinically diagnosed depressed patients. Main effects of sex and age
      significantly predicted CVC such that depressed women had greater CVC and CVC
      decreased with age in the cross-sectional sample. The results suggest greater CVC
      in depressed women might confer cardioprotective functions, which may partially
      explain the sex difference in mortality rates in the depressed population.

PMID- 17204360
TI  - Do panty liners promote vulvovaginal candidiasis or urinary tract infections? A
      review of the scientific evidence.
AB  - Panty liners are used to absorb light menstrual flow, vaginal discharge, or urine
      leakage, or to maintain a clean, dry feeling. Allegations that panty liners may
      trap heat and moisture to promote vulvovaginal candidiasis (VVC) or promote
      colonization by microbes that contribute to urinary tract infections appear to be
      unfounded. As reviewed herein, measurements of the impact of panty liners on skin
      temperature and skin surface moisture had no clinically meaningful effect on cell
      densities of genital microflora. Epidemiological investigations of a potential
      link to VVC were either negative or were inconclusive because of confounding
      factors. Although enteric microbes reside on the vulva and perineum, no evidence
      exists that panty liner use promotes urethral colonization by enteric microbes.
      Moreover, a series of 13 randomized prospective trials of panty liners or ultra
      thin pads demonstrated no clinically significant adverse effects either on the
      skin or on isolation frequencies or cell densities of representative genital
      microflora. Post-market surveillance systems suggest a low incidence of
      complaints. Evidence from vulvar clinic patients reveals no significant
      contribution of these products to persistent vulvar symptoms. Taken together, the
      scientific evidence supports the conclusion that panty liners are safe when used
      as intended and do not promote VVC or urinary tract infections.

PMID- 17204361
TI  - Planning for sustainable tourism in southern Pulau Banggi: an assessment of
      biophysical conditions and their implications for future tourism development.
AB  - A priori assessments of a site's biophysical and socio-economic capacity for
      accommodating tourism are less common than tourism impact studies. A priori
      evaluations can provide a contextual understanding of ecological, economic and
      socio-cultural forces, which shape the prospects for sustainable tourism
      development at the host destination, and can avert adverse impacts of tourism. We
      conduct an a priori assessment of the biophysical environment of Pulau Banggi, in
      the Malaysian state of Sabah for sustainable tourism development. We characterise
      baseline conditions of the island's marine biodiversity, seasonality, and
      infrastructure. We then evaluate how existing biophysical conditions will
      influence options for sustainable tourism development. In particular, we suggest
      conditions, if there are any, which constitute a limit to future tourism
      development in terms of compatibility for recreation and resilience to visitor
      impacts. We find that the biggest constraint is the lack of adequate water and
      sanitation infrastructure. Blast fishing, although occurring less than once per
      hour, can potentially destroy the major attraction for tourists. We conclude that
      while Pulau Banggi possesses natural qualities that are attractive for
      ecotourism, financial and institutional support must be made available to provide
      facilities and services that will enable local participation in environmental
      protection and enhance prospects for future sustainable tourism.

PMID- 17204362
TI  - Genomic comparison using data mining techniques based on a possibilistic fuzzy
      sets model.
AB  - Current copiousness of genomic information stored in biological databases [Mar
      Alba, M., Lee, M., Pearl, D., Shepherd, F.M.G., Martin, A.J., Orengo, N., Kellam,
      C.A., 2001. P. VIDA: a virus database system for the organisation of virus genome
      open reading frames. Nuleic Acids Res. 133-136] makes ultimately feasible the
      proposal for an application of knowledge management aimed to discover general
      rules in subcellular phenomena. The goal of this work is primarily to discover
      relationships between genes by microarray analysis. The tools exploited come from
      clustering techniques and are mainly based on Knowledge Discovery in Databases
      (KDD) concepts [Fayyad, U., Piatetsky-Shapiro, G., Smyth, P., 1996. From data
      mining to knowledge discovery in databases. AI Magazine 17(3), 37-54]. Starting
      from a data set, each element can be represented by a characteristic matrix,
      which sums up all data attributes. In this case data mining is oriented to
      perform a Pattern Recognition of related sequences, hidden in databases [Hand,
      D.J., Nicholas, A., 2005. Heard finding groups in gene expression data. J.
      Biomed. Biotechnol. 215-225]. Following a bottom up approach, the next refinement
      is to compare retrieved data to gather similar features, by dedicated clustering
      algorithms [Kaufman, L., Rousseeuw, P.J., 1990. Finding groups in data. An
      Introduction to Cluster Analysis. John Wiley & Sons, New York; Forman, G., Zhang,
      B., 2000. Distributed Data clustering can be efficient and exact HP. Laboratories
      Palo Alto HPL-2000, p. 158], driven by fuzzy logic, allowing us to perceive by
      intuition a common denominator for various genomic families and to anticipate
      likely future developments.

PMID- 17204363
TI  - A hypothetical role of cortico-basal ganglia-thalamocortical loops in visual
      processing.
AB  - The goal of the present work was to define the mechanisms underlying the
      contribution of sensory and limbic cortico-basal ganglia-thalamocortical loops to
      visual processing and its attentional modulation. We proposed that visual
      processing is promoted by dopamine-dependent long-term modifications of synaptic
      transmission in the basal ganglia that favour a selection of neocortical patterns
      representing a visual stimulus. This selection is the result of the opposite sign
      of modulation of strong and weak cortico-basal ganglia inputs and subsequent
      activity reorganization in each loop. Reorganization leads to
      disinhibition/inhibition of cortical neurons strongly/weakly excited by stimulus
      during dopamine release. Recruitment of the thalamo-basal ganglia-collicular
      pathway is proposed to be necessary for stimulus-evoked dopamine release that
      underlies bottom-up attentional effects. Visual excitation of the prefrontal
      cortex and hippocampus (via the thalamus), their cooperation in control of the
      basal ganglia and dopaminergic cell firing, and simultaneous modulation of
      activity in diverse cortico-basal ganglia-thalamocortical loops is proposed to
      underlie top-down attentional effects. It follows from our model that only those
      components of cortical responses can be modulated by attention, whose onset
      exceeds the latency of visual responses of dopaminergic cells (50-110 ms). This
      and other consequences of the model are in accordance with known experimental
      data.

PMID- 17204364
TI  - Copper and zinc decontamination from single- and binary-metal solutions using
      hydroxyapatite.
AB  - Toxic metals contamination of waters, soils and sediments can seriously affect
      plants, animals and human being. The bioavailability of metal ions can be reduced
      trapping them in minerals with low solubilities. This study investigated the
      sorption of aqueous Cu and Zn onto hydroxyapatite surfaces. Batch experiments
      were carried out using synthetic hydroxyapatite. The metals were applied as
      single or binary species, in a range of metal concentrations ranging from 0 to 8
      mmol/L at 25+/-2 degrees C. The removal capacity of hydroxyapatite was 0.016
      0.764 mmol of Cu/g and 0.015-0.725 mmol of Zn/g. In the Cu-Zn binary system,
      competitive metal sorption occurred with reduction of the removal capacity by 13
      76% and 10-63% for Cu and Zn, respectively, compared to the single-metal systems.
      The sorption of Cu and Zn was well characterized by the Langmuir model. Heavy
      metal immobilization was attributed to a two-step mechanism: first rapid surface
      complexation and secondly partial dissolution of hydroxyapatite and ion exchange
      with Ca followed by the precipitation of a heavy metal-containing hydroxyapatite.

PMID- 17204365
TI  - Osmotic stress on nitrification in an airlift bioreactor.
AB  - The effect of osmotic pressure on nitrification was studied in a lab-scale
      internal-loop airlift-nitrifying reactor. The reactor slowly adapted to the
      escalating osmotic pressure during 270 days operation. The conditions were
      reversed to the initial stage upon full inhibition of the process. Keeping
      influent ammonium concentration constant at 420 mg N L(-1) and hydraulic
      retention time at 20.7h, with gradual increase in osmotic pressure from 4.3 to
      18.8x10(5) Pa by adding sodium sulphate, the ammonium removal efficiencies of the
      nitrifying bioreactor were maintained at 93-100%. Further increase in osmotic
      pressure up to 19.2x10(5) Pa resulted in drop of the ammonium conversion to
      69.2%. The osmotic pressure caused abrupt inhibition of nitrification without any
      alarm and the critical osmotic pressure value causing inhibition remained between
      18.8 and 19.2x10(5) Pa. Nitrite oxidizers were found more sensitive to osmotic
      stress as compared with ammonia oxidizers, leading to nitrite accumulation up to
      61.7% in the reactor. The performance of bioreactor recovered gradually upon
      lowering the osmotic pressure. Scanning and transmission electron microscopy
      indicated that osmotic stress resulted in simplification of the nitrifying
      bacterial populations in the activated sludge as the cellular size reduced; the
      inner membrane became thinner and some unknown inclusions appeared within the
      cells. The microbial morphology and cellular structure restored upon relieving
      the osmotic pressure. Addition of potassium relieved the effect of osmotic
      pressure upon nitrification. Results demonstrate that the nitrifying reactor
      possesses the potential to treat ammonium-rich brines after acclimatization.

PMID- 17204366
TI  - Removal of methylene blue from aqueous solution by dehydrated wheat bran carbon.
AB  - Dyes are usually presents in the effluent water of many industries, such as
      textiles, leather, paper, printing and cosmetics. The effectiveness of dye
      adsorption from wastewater has made to get alternative different low cost
      adsorbent to other expensive treatment methods. The adsorption of methylene blue
      onto dehydrated wheat bran (DWB) was investigated at temperatures (25-45 degrees
      C), initial methylene blue (MB) concentrations (100-500 mg L(-1)) and adsorbent
      dosage at the given contact time for the removal of dye. The optimum adsorption
      conditions were found to be as medium pH of 2.5 and at the temperature of 45
      degrees C for the varying adsorbent dosage. Equilibrium isotherms were analysed
      by Freundlich, Langmuir and Redlich-Peterson isotherm equations using correlation
      coefficients. Adsorption data were well described by the Langmuir model, although
      they could be modelled by the Freundlich and Redlich-Peterson model as well. The
      pseudo-first order and pseudo-second order kinetic models were applied to test
      the experimental data. It was concluded that the pseudo-second order kinetic
      model provided better correlation of the experimental data rather than the pseudo
      first order model. The mass transfer model as intraparticle diffusion was applied
      to the experimental data to examine the mechanisms of rate controlling step. It
      was found that at the higher initial MB concentration, intraparticle diffusion is
      becoming significant controlling step. The thermodynamic constants of the
      adsorption process were also evaluated by using the Langmuir constants related to
      the equilibrium of adsorption at temperatures varied in the range 25-55 degrees
      C.

PMID- 17204367
TI  - Use of cement and quicklime to accelerate ripening and immobilize contaminated
      dredging sludge.
AB  - In this study cement and quicklime are examined as binders to enhance the
      ripening process and immobilize contaminants in dredging sludge. Ripening
      comprises the drying in the open air till a dry matter content of 50-55% is
      reached. For this study, a dredging sludge of the highest contamination category
      was used. The binders speed up the ripening process substantially since the
      binders as such increase the dry matter content upon mixing, but they also modify
      the structure so that evaporation is facilitated. Furthermore, the reaction of
      cement and quicklime with water generates heat that also stimulates evaporation,
      and both binders, in combination with dredging sludge, bind water chemically
      (twice as much as expected). The total time for ripening could be reduced by 70%,
      which means that existing treatment depots can be used more effectively. The
      emission of contaminants was determined by a standard leaching test. The cement
      and quicklime had opposite effects on the leaching of constituents. The addition
      of cement had negative effects on sulphate, fluoride, and zinc, which were
      compensated by the addition of quicklime. On the other hand, cement reduced the
      emission of chloride, copper, and nickel, while quicklime seemed to increase the
      emission of these constituents. The concentration and emission of contaminants of
      the treated dredging sludge meet the requirements of the current legislation. It
      is therefore concluded that the presented method is able to produce, in a much
      shorter time, an applicable building material from contaminated dredging sludge.

PMID- 17204368
TI  - Ambiguous words in sentences: brain indices for native and non-native
      disambiguation.
AB  - In the present study, we compare how native speakers and second language learners
      process homonyms (such as bank and jam) in sentence context during a late
      processing phase that involves selection of the appropriate meaning. With both
      participant groups, we conducted a combined reaction time (RT)/event-related
      brain potential (ERP) lexical decision experiment with a long stimulus-onset
      asynchrony (SOA) of 800 ms. Related primes were homonyms at the end of sentences
      with a context biasing one of the homonym meanings, and targets reflected the
      contextually appropriate or inappropriate meaning. Both RT and ERP semantic
      priming in the N400 component revealed that for both natives and learners, only
      contextually appropriate meanings were primed, or still active, late in
      processing. The results indicate that L2 learners show similar, though slower,
      homonym processing mechanisms to those of native speakers of a language, and that
      both groups can achieve disambiguation based on semantic context.

PMID- 17204369
TI  - Phenotypic associations of tau and ApoE in Parkinson's disease.
AB  - Overlaps in clinical, pathological and molecular features of Parkinson's disease
      (PD), dementing and motor tauopathies have prompted association studies in search
      of common genetic risk factors that may predispose or modify this spectrum of
      disorders. To explore possible phenotypic implications, we studied common tau and
      ApoE gene polymorphisms, associated with Alzheimer's disease (AD), progressive
      supranuclear palsy (PSP) and PD, in a clinically and pathologically characterized
      cohort of PD patients and aged control subjects. Our results reveal a novel
      association between PD-related hallucinations and H1H1 genotype. We also report
      an association between PDD and the presence of the ApoE epsilon4 allele. Better
      determination of subsets of PD patients based upon the presence of specific
      phenotypic features may improve the accuracy of association studies.

PMID- 17204370
TI  - Is there a tipping point in neuronal ensembles during learning?
AB  - Learning is important for humans and can be disrupted by disease. However, the
      essence of how learning may be represented within a neuronal network is still
      elusive. Spike trains generated by neurons have been demonstrated to carry
      information which is relevant for learning. The present study uses well
      established mutual information (MI) analysis techniques to better understand
      learning within neuronal ensembles. Spike trains in tetrode recordings from the
      dorso-lateral striatum were used for computing MI as rats learnt a T-maze
      procedural task. We demonstrate that in in-vivo recordings the growth of MI is
      reflected in the behavioral response as learning proceeds. These changes in MI
      are seen to correspond to three phases, a low MI value, namely early learning, a
      rapid increase in MI value, task-acquisition and stabilization of MI, over
      training. Over multiple training sessions, small changes in MI within the
      neuronal network suddenly produce a big change in ensemble MI during the task
      acquisition phase. This phase represents the "tipping point" in the neuronal
      network where the MI growth builds habits during motor learning in the striatum.

PMID- 17204371
TI  - Differential expression of NF-kappaB in mycobacteria infected THP-1 affects
      apoptosis.
AB  - The present study was conducted to see the role of NF-kappaB in virulent
      (Mycobacterium tuberculosis H37Rv) and avirulent (M. tuberculosis H37Ra)
      mycobacterial infection in THP-1 cells. To inactivate NF-kappaB, pCMV
      IkappaBalphaM dn containing THP-1 cell line was generated which showed marked
      increase in apoptosis with M. tuberculosis H37Rv and M. tuberculosis H37Ra.
      Infected THP-1-IkappaBalphaM dn cells showed decrease in mitochondrial membrane
      potential, cytochrome c release, activation of caspase-3 and enhanced TNF-alpha
      production. Increase in apoptosis of infected THP-1-IkappaBalphaM dn cells
      resulted in inhibition of intracellular mycobacterial growth. Differential NF
      kappaB activation potential was observed with M. tuberculosis H37Rv and M.
      tuberculosis H37Ra. Both the strains activated NF-kappaB after 4 h in THP-1 cells
      however after 48 h only M. tuberculosis H37Rv activated NF-kappaB which lead to
      up-regulation of bcl-2 family anti-apoptotic member, bfl-1/A1. Our results
      indicated that NF-kappaB activation may be a determinant factor for the success
      of virulent mycobacteria within macrophages.

PMID- 17204372
TI  - Developmental changes in odor-evoked activity in rat piriform cortex.
AB  - In adult rats, odor-evoked Fos protein expression is found in rostrocaudally
      oriented bands of cells in anterior piriform cortex (APC), likely indicating
      functionally distinct subregions, while activated cells in posterior piriform
      cortex (PPC) lack apparent spatial organization. To determine whether these
      patterns are present during early postnatal life, and whether they change during
      development, Fos expression was assessed following acute exposure to single
      aliphatic acid odors in developing rats beginning at postnatal day 3 (P3). In the
      olfactory bulb, Fos-immunoreactive cells were present in the granule cell, mitral
      cell and glomerular layers at the earliest ages examined. Cells immunopositive
      for Fos were clustered in areas previously reported as active in response to
      these odors. In piriform cortex, activation in layers II/III shared some features
      with that seen in the adult; in APC, rostro-caudally oriented bands of Fos
      positive cells alternated with bands relatively free of label, while labeled
      cells were found dispersed throughout PPC. However, in P3-P7 animals, Fos
      positive cells in APC were found in a central rostro-caudally oriented band that
      was flanked by two bands relatively free of Fos-positive cells. This contrasted
      with the adult pattern, a central cell-poor band flanked by cell-rich bands,
      which was observed beginning at P10. These results suggest that subregions of APC
      visualized by odor-evoked Fos expression are active and functionally distinct
      shortly after birth. Changes in activity within these subregions during early
      postnatal development coincide with a shift toward adult-like olfactory learning
      behavior in the second postnatal week, and may play a role in this behavioral
      shift.

PMID- 17204373
TI  - Orbitofrontal cortex lesions disrupt risk assessment in a novel serial decision
      making task for rats.
AB  - Neurobiological mechanisms of decision-making have been shown to be modulated by
      a number of frontal brain regions. Among those areas, the orbitofrontal cortex
      (OFC) is thought to play an important role in the decision of behavioral actions
      when faced with alternative options of ambiguous outcome. Here we present a novel
      neurobehavioral task to study affective decision-making in the rat, based on
      evaluation of consecutive choices between two levers associated with rewards of
      different value and probability. Two groups of animals were studied; a sham
      control group (n=6) and an OFC-lesioned group (n=7). In the first 30 trials both
      groups had similar preference patterns but at the end of the 90 trials of the
      task both groups developed specific preferences. The control group systematically
      preferred the lever associated with smaller but more reliable rewards (low risk
      lever) while the OFC lesion group preferred the high risk lever (index of
      preference of 0.21+/-0.21 vs. -0.45+/-0.10; t-test, P<0.05). Analysis of choice
      persistence (i.e. choosing the same lever in consecutive trials) suggests that
      the OFC-lesioned group became less sensitive to risk, seeking large rewards
      irrespective of their success probability.

PMID- 17204375
TI  - Conservative evolution in duplicated genes of the primate Class I ADH cluster.
AB  - Humans have seven alcohol dehydrogenase genes (ADH) falling into five classes.
      Three out of the seven genes (ADH1A, ADH1B and ADH1C) belonging to Class I are
      expressed primarily in liver and code the main enzymes catalyzing ethanol
      oxidization. The three genes are tandemly arrayed within the ADH cluster on
      chromosome 4 and have very high nucleotide similarity to each other (exons: >90%;
      introns: >70%), suggesting the genes have been generated by duplication event(s).
      One explanation for maintaining similarity of such clustered genes is
      homogenization via gene conversion(s). Alternatively, recency of the duplications
      or some other functional constraints might explain the high similarities among
      the genes. To test for gene conversion, we sequenced introns 2, 3, and 8 of all
      three Class I genes (total>15.0 kb) for five non-human primates--four great apes
      and one Old World Monkey (OWM)--and compared them with those of humans. The
      phylogenetic analysis shows each intron sequence clusters strongly within each
      gene, giving no evidence for gene conversion(s). Several lines of evidence
      indicate that the first split was between ADH1C and the gene that gave rise to
      ADH1A and ADH1B. We also analyzed cDNA sequences of the three genes that have
      been previously reported in mouse and Catarrhines (OWMs, chimpanzee, and humans)
      and found that the synonymous and non-synonymous substitution (dN/dS) ratios in
      all pairs are less than 1 representing purifying selection. This suggests that
      purifying selection is more important than gene conversion(s) in maintaining the
      overall sequence similarity among the Class I genes. We speculate that the highly
      conserved sequences on the three duplicated genes in primates have been achieved
      essentially by maintaining stability of the hetero-dimer formation that might
      have been related to dietary adaptation in primate evolution.

PMID- 17204374
TI  - Severity of alcohol-induced painful peripheral neuropathy in female rats: role of
      estrogen and protein kinase (A and Cepsilon).
AB  - Small-fiber painful peripheral neuropathy, a complication of chronic ethanol
      ingestion, is more severe in women. In the present study, we have replicated this
      clinical finding in the rat and evaluated for a role of estrogen and second
      messenger signaling pathways. The alcohol diet (6.5% ethanol volume:volume in
      Lieber-DeCarli formula) induced hyperalgesia with more rapid onset and severity
      in females. Following ovariectomy, alcohol failed to induce hyperalgesia in
      female rats, well past its time to onset in gonad intact males and females.
      Estrogen replacement reinstated alcohol neuropathy in the female rat. The protein
      kinase A (PKA) inhibitor (Walsh inhibitor peptide, WIPTIDE) only attenuated
      alcohol-induced hyperalgesia in female rats. Inhibitors of protein kinase
      Cepsilon (PKCepsilon-I) and extracellular-signal related kinase (ERK) 1/2 (2'
      amino-3'-methoxyflavone (PD98059) and 1,4-diamino-2, 3-dicyano-1, 4-bis (2
      aminophenylthio) butadiene (U0126)) attenuated hyperalgesia in males and females,
      however the degree of attenuation produced by PKCepsilon-I was much greater in
      females. In conclusion, estrogen plays an important role in the expression of
      pain associated with alcohol neuropathy in the female rat. In contrast to
      inflammatory hyperalgesia, in which only the contribution of PKCepsilon signaling
      is sexually dimorphic, in alcohol neuropathy PKA as well as PKCepsilon signaling
      is highly sexually dimorphic.

PMID- 17204376
TI  - Use of an insect cell culture growth medium to isolate bacteria from horses with
      effusive, fibrinous pericarditis: a preliminary study.
AB  - Effusive, fibrinous pericarditis is an uncommon disease entity in horses. In
      2001, pericarditis occurred in conjunction with an epizootic in central Kentucky
      that was associated with exposure to eastern tent caterpillars (ETCs). Bacterial
      isolation from equine pericardial fluid samples was attempted using an insect
      cell culture growth medium (ICCGM). Using previously cultured, stored frozen
      samples from four horses with fibrinous pericarditis, inoculation of 10% blood
      agar plates yielded no growth, whereas simultaneous inoculation of ICCGM resulted
      in the isolation of Proprionibacterium acnes, Staphylococcus equorum, a
      Streptococcus sp. and Pseudomonas rhodesiae from pericardial fluid samples. A
      similar or novel caterpillar-associated bacteria was not identified; however, use
      of an ICCGM might enhance isolation of bacteria from equine pericardial fluid.

PMID- 17204377
TI  - Nuclear and cytoskeletal dynamics during oocyte maturation and development of
      somatic cell cloned pig embryos injected with membrane disintegrated donor cells.
AB  - The objectives of this study were to characterize the nuclear and cytoskeletal
      changes of pig oocytes during in vitro maturation (IVM) and the development of
      the reconstructed embryos after injection with membrane intact or disintegrated
      donor cells. Cumulus-oocyte complexes (COCs) were collected from abattoir ovaries
      by follicle (2-8mm) aspiration. In Experiment 1, COCs were cultured in NCSU-23
      medium for 0, 11, 22, 33, and 44 h. Oocytes were fixed at different time points
      for nuclear and cytoskeletal labeling. Forty-three percent and 75% oocytes
      progressed to MII stage at 33 and 44 h after IVM culture, respectively. Dynamic
      shift of spindle and cytoplasmic microtubules was evident. In Experiment 2,
      matured oocytes were injected with either the whole cumulus cell with or without
      intact cell membranes after enucleation. The reconstructed oocytes were fixed at
      0, 2, or 4 h after cell injection for nuclear and cytoskeletal evaluation. When
      an intact cumulus cell was injected, the injected cell remained intact within 4h
      after injection. When a cell with disintegrated membrane was injected, 59-63%
      (n=146) of the injected cell underwent premature chromosome condensation (PCC).
      In Experiment 3, the reconstructed pig oocytes received membrane-disintegrated
      cumulus cells or fetal fibroblasts were cultured in PZM medium. The blastocyst
      rate of the fibroblast-injected embryos was 10%, which was lower than the non
      cloned parthenotes (33%, P<0.05) but higher than the cumulus cell-injected
      embryos (2.7%). These results suggest that pig oocytes are subjected to nuclear
      and cytoskeletal reorganization during maturation. Pig oocytes injected with
      membrane-disintegrated fibroblast cells support better blastocyst development of
      the cloned embryos.

PMID- 17204378
TI  - Interspecific embryo transfer from mouflon (Ovis gmelini musimon) to domestic
      Corriedale sheep in Argentina.
AB  - An interspecific embryo transfer program was conducted for genetic improvement
      and increasing the number of offspring from a flock of mouflon sheep in
      Argentina. The female donor mouflons were divided into three groups, G1 (n=5), G2
      (n=4) and G3 (n=5). The total NIH-FSH-P1 dose given to each donor on the
      superovulatory treatment was 260, 200 and 160 mg for G1, G2 and G3, respectively.
      The mouflons in G3 were maidens, while the others were multiparous. Domestic
      Corriedale ewes (n=60) were synchronized and used as recipients. The embryo
      recovery and transfer was performed by a surgical method. Mouflons (n=13)
      responded to the superovulatory treatment with an average of 9.1+/-2.8
      ovulations. A low incidence of early luteal regression was found (1 out of 14
      donors). Embryo recovery rates were 60, 31 and 76% in groups G1, G2 and G3,
      respectively. The percentage of transferable embryos obtained in G1 and in G2
      exceeded 80%. None of the embryos obtained from G3 were of transferable quality.
      In G1, 25 transferable embryos were recovered and transferred to 13 recipients,
      resulting in a pregnancy rate of 76.9% (10/13). In G2, 10 embryos were
      transferred to 5 recipients, resulting in a 60% pregnancy rate (3/5). Lambing
      rate was 60% (15/25) and 30% (3/10) for G1 and G2, respectively. Thirteen lambs
      were born to the 14 donors following natural service after the embryo recoveries.
      This study demonstrates that the application of IET technology would have great
      reproductive impact, especially when the donor mouflon hinds are selected
      according to age and reproductive history.

PMID- 17204379
TI  - Analysis of prion protein genotypes in relation to reproduction traits in local
      and cosmopolitan German sheep breeds.
AB  - Due to the genetic determination of susceptibility to scrapie and other forms of
      transmissible spongiform encephalopathy (TSE) in sheep breeding to the less
      susceptible prion protein (PrP) genotype ARR/ARR was advanced within EU. In 4961
      ewes of nine German sheep breeds (Coburg Fox sheep, Gray Horned Heath sheep,
      Merinoland sheep, Rhoen sheep, German Blackheaded Mutton sheep, Shropshire,
      Suffolk, Texel and White East Friesian Milk sheep) representing local and
      cosmopolitan breeds the reproductive traits number of lambs born, dead (including
      abortion at the end of pregnancy, stillbirth and death during the first 56 days
      post natum), weaned and rearing rate at each lambing were recorded and in 1641 of
      these ewes the PrP genotype was determined. A linear model was used to evaluate
      associations between PrP genotype and reproduction traits including the effects
      of PrP genotype (four classes: ewes with two, one and no copy of the ARR allele
      and with unknown PrP genotype), breed, interaction of PrP genotype and breed,
      number of lambing, lambing season and stock. Significant associations were only
      observed between the PrP genotype and the number of dead lambs at each lambing in
      Shropshire and Merinoland sheep and the rearing rate at each lambing in
      Shropshire. These significant associations were mainly caused by differences
      between animals with unknown PrP genotype and animals of the other PrP classes.
      In conclusion, breeding for TSE resistant sheep will not lead to a reduction in
      economically important reproduction traits.

PMID- 17204380
TI  - Identification of novel pregnancy-associated glycoproteins (PAG) expressed by the
      peri-implantation conceptus of domestic ruminants.
AB  - Pregnancy-associated glycoproteins (PAG) are a multigene family, related to
      aspartic proteinases, expressed in the placenta of artiodactyls. Ruminant PAG
      expression varies spatially as well as temporally during gestation. The aim of
      this study was the identification of novel PAG expressed around implantation in
      domestic ruminants and to study their phylogenetic relationships. Day 12, 14, 17
      (ovine); day 15, 18 (bovine); and day 12, 14, 15, 16, 18 (caprine) conceptuses
      were used for reverse transcription-polymerase chain reaction (RT-PCR) performed
      on RNA extracted from conceptuses pooled on each day of recovery. In ovine, a
      single PAG was detected on day 14, ovPAG2, from the PAG II group. On day 17,
      three more PAG were identified. One of them similar to ovPAG1 and two unknown
      named as ovPAG10 and ovPAG11, apparently from the PAG I group. In bovine, PAG
      expression was detected by day 15 and two transcripts were identified on day 18.
      One, boPAG2, from the PAG II group and other was previously unknown, boPAG22,
      closest to boPAG2. In goats, PAG expression was not detected on non-elongated
      conceptuses (days 12, 14 and 15). Two different transcripts were identified in
      both day 16 and 18 elongated conceptuses, one similar to caPAG2, from the PAG II
      group, whereas the other, caPAG12, apparently from the PAG I group, was
      previously unknown. Interestingly, the three new early PAG identified in sheep
      and goats are clustered together within the PAG I group. In summary, a complement
      of new PAGs expressed at implantation in domestic ruminants has been cloned.

PMID- 17204381
TI  - Is there a relationship between prion protein genotype and ovulation rate and
      litter size in sheep?
AB  - The identification of an association between polymorphisms of the prion protein
      (PrP) gene and susceptibility to scrapie has enabled the development of breeding
      programmes to increase natural resistance to scrapie. It is, however, imperative
      to identify if such selection would affect important reproduction and production
      traits. The objective of this study was to determine if there is a relationship
      between polymorphisms at codons 136, 154 and 171 of the PrP gene and ovulation
      rate or litter size in sheep. Data were collected from a mixed-aged flock of
      Belclare ewes, over a 9-year period. Ovulation rate was determined annually using
      laparoscopy by counting the number of corpora lutea at each of two consecutive
      oestrous cycles, one immediately before and one after mating (2418 records from
      366 ewes). Litter size was recorded at parturition (875 records from 353 ewes).
      The five common PrP alleles were present in the population and 14 PrP genotypes
      were represented among the animals studied. There was no significant overall
      effect of PrP genotype on ovulation rate or litter size and pairwise comparisons
      among genotypes did not reveal any significant differences for either trait.
      These data suggest that breeding programmes based on selection for specific
      polymorphisms of the PrP gene will not influence ovulation rate or litter size,
      at least in the breed studied.

PMID- 17204382
TI  - Influence of membrane-solvent-solute interactions on solute permeation in model
      membranes.
AB  - The interaction of the components of topical formulations with the skin is an
      important consideration for effective drug delivery and efficacy. The relative
      importance of solubility parameters and other solvent properties on membrane
      diffusion processes has not been fully elucidated in the literature. In this
      paper, the effect of different vehicles on the permeation of caffeine, salicylic
      acid and benzoic acid through silicone membranes was evaluated.
      Polydimethylsiloxane membranes were used as model membranes for comparing the
      release characteristics of saturated solutions of model permeants because of
      their homogeneity and uniformity. Log P (octanol-water partition coefficient) and
      solubility parameter values were calculated for the compounds under study. In
      vitro diffusion studies indicated that the permeation profiles of all solutes
      showed a similar pattern. The permeation rates of benzoic acid and salicylic acid
      through silicone membrane from saturated solutions were higher than those for
      caffeine reflecting the more lipophilic nature of these compounds in comparison
      with caffeine. Solvent uptake studies confirmed that the vehicles that were
      highly sorbed by the membrane altered its properties and hence the flux. Vehicles
      that were not sorbed by the membrane showed similar steady-state fluxes for the
      model drugs. This suggests that the diffusion process is mainly influenced by the
      interactions between the vehicles and the membrane. Solubility parameter alone
      cannot explain the interactions between the membrane and the vehicles in all
      cases. Rather, it is likely that membrane flux reflects a combination of
      different solvent and solute characteristics, such as size, shape and charge
      distribution.

PMID- 17204384
TI  - Vasodilator effect of the extracts and some coumarins from the stem bark of
      Mammea africana (Guttiferae).
AB  - CH(2)Cl(2) fraction obtained from the stem bark of Mammea africana inhibited
      noradrenaline (NA) or KCl-induced contraction in isolated guinea pig and rat
      aorta. The vasorelaxant potency of the CH(2)Cl(2) fraction of Mammea africana was
      diminished by a pre-treatment with Nitro-L-arginine methyl ester (L-NAME), an
      inhibitor of NO synthase, which was however not affected by indomethacin pre
      treatment. These findings indicated that the vasorelaxant effect of Mammea
      africana may be partially endothelium dependent, mediated by nitric oxide and
      that vasoactive prostanoids might not be contributing to the vasorelaxation
      effect. Three bioactive compounds were isolated from this CH(2)Cl(2) fraction and
      identified as 4-n-propylcoumarins (1) (mammea B/BB), 4-phenylcoumarins (2)
      (mammea A/AA or mammeisin) and (B/BA) (3) and might involved in the vasorelaxant
      effect of the extract. The mechanisms of the vasorelaxant effect might therefore
      be multiple, including endothelium dependence and the mechanisms, which interfere
      with the liberation of Ca(2+) into the muscle cell.

PMID- 17204385
TI  - Treatment with total alkaloids from Radix Linderae reduces inflammation and joint
      destruction in type II collagen-induced model for rheumatoid arthritis.
AB  - Radix Linderae, the dry roots of Lindera aggregata (Sims) Kosterm., is frequently
      used in traditional Chinese medicine. It contains alkaloids, volatile oils and
      sesquiterpene esters. In the present study, we investigated the therapeutic
      potential and underlying mechanisms of the total alkaloids from Radix Linderae
      (TARL) on collagen II (CII)-induced arthritis (CIA) in mice. TARL (50, 100 and
      200mg/kg), orally administered on the same day of an antigen challenge for 20
      consecutive days, alleviated disease severity in a dose-dependent manner but did
      not significantly affect body weights. The TARL treatment reduced the serum level
      of anti-CII IgG and suppressed the delayed type hypersensitivity evaluated by its
      effect against CII-induced ear swelling. TARL also protected joint destruction
      based on the evidence of reducing the histopathological scores. Furthermore, TARL
      suppressed CII- and concanavalin A-stimulated lymphocyte proliferation in
      popliteal lymph nodes, where are close to the affected joints in CIA. These data
      suggest that TARL is a potential therapeutic agent for rheumatoid arthritis that
      suppresses inflammation and protects joints from destruction.

PMID- 17204383
TI  - Myosin VI and VIIa distribution among inner ear epithelia in diverse fishes.
AB  - Unconventional myosins are critical motor proteins in the vertebrate inner ear.
      Mutations in any one of at least six different myosins can lead to human
      hereditary deafness, but the precise functions of these proteins in the ear are
      unknown. This study uses a comparative approach to better understand the role of
      myosins VI and VIIa in vertebrate ears by examining protein distribution for
      these two myosins in the ears of evolutionarily diverse fishes and the aquatic
      clawed toad Xenopus laevis. Both myosins are expressed in the inner ears of all
      species examined in this study. Myo7a localizes to hair cells, particularly the
      actin-rich hair bundle, in all species studied. Myo6 also localizes to hair
      cells, but its distribution differs between species and end organs. Myo6 is found
      in hair bundles of most fish and frog epithelia examined here but not in anterior
      and posterior utricular hair bundles of American shad. These results show that
      myo7a distribution is highly conserved in diverse vertebrates and suggest
      functional conservation as well. The finding of myo6 in fish and Xenopus hair
      bundles, however, suggests a novel role for this protein in anamniotic hair
      cells. The lack of myo6 in specific American shad utricular hair bundles
      indicates a unique quality of these cells among fishes, perhaps relating to
      ultrasound detection capability that is found in this species.

PMID- 17204386
TI  - Synergistic activation of monocytes by polysaccharides isolated from Salicornia
      herbacea and interferon-gamma.
AB  - The hot water extract of Salicornia herbacea, SHE, has recently been shown to
      have strong immunomodulatory activity. In the present study, we purified the
      polysaccharides, termed SHP, from SHE preparation and examined their
      immunomodulatory activity alone and in combination with interferon (IFN)-gamma.
      The combination of SHP and IFN-gamma synergistically inhibited the growth of the
      mouse monocytic cell line, RAW 264.7, inducing further differentiation to
      strongly adherent macrophages. The differentiation-inducing activity of SHP alone
      and in combination with IFN-gamma was confirmed by changes in the expression of
      differentiation antigens such as CD11b, CD18 and CD24. In addition, the
      combination of SHP and IFN-gamma synergistically activated RAW cells to produce
      cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta,
      and nitric oxide (NO). The synergistic activity of SHP was more prominent when
      SHP concentration was low. Increased production of TNF-alpha, IL-1 beta and NO
      was correlated with an increased level of their respective transcripts. These
      results confirm that Salicornia herbacea contains immunomodulatory
      polysaccharides that activate monocytes synergistically with small doses of IFN
      gamma.

PMID- 17204387
TI  - Quantitative temporal lobe differences: autism distinguished from controls using
      classification and regression tree analysis.
AB  - The temporal lobe is thought to be abnormal in autism, yet standard volumetric
      analyses are often unrevealing when age, sex, IQ, and head size are controlled.
      Quantification of temporal lobe structures were obtained in male subjects with
      autism and controls, where subjects with head circumference (HC) defined
      macrocephaly were excluded, so that volume differences were not just related to
      the higher prevalence of macrocephaly in autism. Various statistical methods were
      applied to the analysis including a classification and regression tree (CART)
      method, a non-parametric technique that helps define patterns of relationships
      that may be meaningful in distinguishing temporal lobe differences between
      subjects with autism and age and IQ matched controls. Subjects with autism were
      also compared to a separate control group with reading disorder (RD), with the
      prediction that the temporal lobe morphometric analysis of the reading disorder
      controls would be more similar to that of the autism group. The CART method
      yielded a high specificity in classifying autism subjects from controls based on
      the relationship between the volume of the left fusiform gyrus (LFG) gray and
      white matter, the right temporal stem (RTS) and the right inferior temporal gyrus
      gray matter (RITG-GM). Reading disordered individuals were more similar to
      subjects with autism. Simple size differences did not distinguish the groups.
      These findings demonstrate different relationships within temporal lobe
      structures that distinguish subjects with autism from controls. Results are
      discussed in terms of pathological connectivity within the temporal lobe as it
      relates to autism.

PMID- 17204388
TI  - Caloric restriction reduces age-related pseudocapillarization of the hepatic
      sinusoid.
AB  - Age-related changes in the hepatic sinusoid, called pseudocapillarization, may
      contribute to the pathogenesis of dyslipidemia. Caloric restriction (CR) is a
      powerful model for the study of aging because it extends lifespan. We assessed
      the effects of CR on the hepatic sinusoid to determine whether
      pseudocapillarization is preventable and hence a target for the prevention of age
      related dyslipidemia. Livers from young (6 months) and old (24 months) CR and ad
      libitum fed (AL) F344 rats were examined using electron microscopy and
      immunohistochemistry. In old age, there was increased thickness of the liver
      sinusoidal endothelium and reduced endothelial fenestration porosity. In old CR
      rats, endothelial thickness was less and fenestration porosity was greater than
      in old AL rats. Immunohistochemistry showed that CR prevented age-related
      decrease in caveolin-1 expression and increase in peri-sinusoidal collagen IV
      staining, but did not alter the age-related increase of von Willebrand's factor.
      CR reduces age-related pseudocapillarization of the hepatic sinusoid and
      correlates with changes in caveolin-1 expression.

PMID- 17204389
TI  - Regular exercise reduces 8-oxodG in the nuclear and mitochondrial DNA and
      modulates the DNA repair activity in the liver of old rats.
AB  - Exercise is often said to increase the generation of reactive oxygen species that
      are potentially harmful. On the other hand, regular exercise has various health
      benefits even late in life. The specific aim of this study was to explore effects
      of regular exercise on oxidative status of DNA in aged animals. We report that 2
      months of regular treadmill running of aged rats (21 month old) significantly
      reduced 8-oxodG content to the level of young adult animals (11 month old) in
      both nuclear and mitochondrial DNA of the liver. The mitochondrial DNA showed 10
      fold higher content of the oxidative lesion than the nuclear DNA. The levels in
      old animals were 2- and 1.5-fold higher than that in young adults for the nucleus
      and mitochondria, respectively. The activity of the repair enzyme OGG1 was
      upregulated significantly in the nucleus but not in mitochondria by the exercise.
      To our knowledge, this is the first report demonstrating that regular exercise
      can reduce significantly oxidative damage to both the nuclear and mitochondrial
      DNA. We suggest that the apparent beneficial outcomes in reducing the DNA damage
      by regular exercise can be interpreted in terms of hormetic effect by moderate
      oxidative stress and potential adaptation to stronger stresses.

PMID- 17204390
TI  - Gene expression and generation of CD28-CD8 T cells mediated by interleukin 15.
AB  - Accumulation of CD28(-)CD8 T cells that are defective in response to antigenic
      stimulation is a hallmark of age-associated decline in T cell function. However,
      the underlying mechanism of this age-associated change is not fully understood.
      We recently analyzed the global gene expression profiles of CD8 T cell subsets
      from nai ve to memory (CD28(+) to CD28(-)) cells and the growth of CD28(+) and
      CD28(-)CD8 memory T cells in response to homeostatic cytokine interleukin 15 (IL
      15). At the gene expression level, one of the most striking changes is the
      altered expression of some co-stimulatory receptors and various NK cell receptors
      in CD28(-)CD8 T cells. Furthermore, CD28(-)CD8 T cells appear to have a normal
      proliferation response to IL-15 in vitro. Interestingly, IL-15 is also capable of
      inducing stable loss of CD28 expression in actively dividing CD28(+)CD8 memory T
      cells. Together, these findings provide the gene expression features of CD28(
      )CD8 T cells that differ from their CD28(+) counterparts and suggest a possible
      role of IL-15 in the increase of CD28(-)CD8 T cells that occurs with aging.

PMID- 17204391
TI  - Aging and estrogen: modulation of inflammatory responses after injury.
AB  - Aged subjects have a poor prognosis after traumatic injury and, regardless of the
      type of injury, they have slower recoveries and suffer more complications than
      their younger counterparts. The age-dependent responses may be influenced by the
      hyper-inflammatory state observed in the aged prior to injury, including elevated
      levels of interleukin-6 (IL-6). Physiological levels of estrogen are beneficial
      to the immune system, due, in part, to the hormone's ability to attenuate
      aberrant production of pro-inflammatory cytokines. Using two independent injury
      models, we have found increased mortality and elevated serum levels of IL-6 in
      aged mice, when compared to young animals (p<0.05). In parallel studies, groups
      of aged mice given estrogen (17beta-estradiol) prior to scald burn, had
      significantly improved survival (p<0.05) and lowered serum IL-6 (p<0.05).
      Multiple cellular mechanisms may be involved in mediating the beneficial effects
      of estrogen on inflammatory and immune responses in aged individuals who sustain
      an injury. These mechanisms are discussed herein.

PMID- 17204392
TI  - Liquid-liquid extraction of strongly protein bound BMS-299897 from human plasma
      and cerebrospinal fluid, followed by high-performance liquid
      chromatography/tandem mass spectrometry.
AB  - BMS-299897 is a gamma-secretase inhibitor that is being developed for the
      treatment of Alzheimer's disease. Liquid-liquid extraction (LLE),
      chromatographic/tandem mass spectrometry (LC/MS/MS) methods have been developed
      and validated for the quantitation of BMS-299897 in human plasma and
      cerebrospinal fluid (CSF). Both methods utilized (13)C6-BMS-299897, the stable
      label isotope analog, as the internal standard. For the human plasma extraction
      method, two incubation steps were required after the addition of 5 mM ammonium
      acetate and the internal standard in acetonitrile to release the analyte bound to
      proteins prior to LLE with toluene. For the human CSF extraction method, after
      the addition of 0.5 N HCl and the internal standard, CSF samples were extracted
      with toluene and no incubation was required. The organic layers obtained from
      both extraction methods were removed and evaporated to dryness. The residues were
      reconstituted and injected into the LC/MS/MS system. Chromatographic separation
      was achieved isocratically on a MetaChem C18 Hypersil BDS column (2.0 mm x 50 mm,
      3 microm). The mobile phase contained 10 mM ammonium acetate pH 5 and
      acetonitrile. Detection was by negative ion electrospray tandem mass
      spectrometry. The standard curves ranged from 1 to 1000 ng/ml for human plasma
      and 0.25-100 ng/ml for human CSF. Both standard curves were fitted to a 1/x
      weighted quadratic regression model. For both methods, the intra-assay precision
      was within 8.2% CV, the inter-assay precision was within 5.4% CV, and assay
      accuracy was within +/-7.4% of the nominal values. The validation and sample
      analysis results demonstrated that both methods had acceptable precision and
      accuracy across the calibration ranges.

PMID- 17204393
TI  - Multiple bombesin-like peptides with opposite functions from skin of Odorrana
      grahami.
AB  - Bombesin-like peptides (BLPs) are a family of neuroendocrinic peptides that
      mediate a variety of biological activities. Three mature BLPs from the skin
      secretions of the frog Odorrana grahami were purified. Several bombesin-like
      peptide cDNA sequences encoding precursors of BLPs were identified from the skin
      cDNA library of O. grahami. This is the maximal diversity of BLPs ever found in
      animals. Five mature BLPs (B1-B5) based on the amino acid sequences derived from
      the cDNA cloning were synthesized. In the in vitro myotropic contraction
      experiment, all synthesized BLPs displayed a stimulating effect toward rat
      stomach strips, except B4 and B5 which showed the opposite effect, suggesting
      that certain BLPs may act as antagonists of bombesin receptors while most other
      BLPs act as agonists. This finding will facilitate the finding of novel bombesin
      receptors and novel ligands of bombesin receptors. The diversity of amphibian
      BLPs and their precursors were also analyzed and results suggest that amphibian
      BLPs and corresponding precursors of various sizes and processing patterns can be
      used as markers of taxonomic and molecular phylogenetics. The remarkable
      similarity of preproregions gives rise to very different BLPs and 3'-terminal
      regions in distantly related frog species, suggesting that the corresponding
      genes form a multigene family originating from a common ancestor. The
      diversification of BLP loci could thus be part of an evolutionary strategy
      developed by amphibian species as a result of shifts to novel ecological niches
      when environmental factors change rapidly.

PMID- 17204394
TI  - Interleukin-6 mediates low-threshold mechanical allodynia induced by intrathecal
      HIV-1 envelope glycoprotein gp120.
AB  - Spinal cord glia (microglia and astrocytes) contribute to enhanced pain states.
      One model that has been used to study this phenomenon is intrathecal (i.t.)
      administration of gp120, an envelope glycoprotein of HIV-1 known to activate
      spinal cord glia and thereby induce low-threshold mechanical allodynia, a pain
      symptom where normally innocuous (non-painful) stimuli are perceived as painful.
      Previous studies have shown that i.t. gp120-induced allodynia is mediated via the
      release of the glial pro-inflammatory cytokines, tumor necrosis factor-alpha
      (TNF), and interleukin-1beta (IL-1). As we have recently reported that i.t. gp120
      induces the release of interleukin-6 (IL-6), in addition to IL-1 and TNF, the
      present study tested whether this IL-6 release in spinal cord contributes to
      gp120-induced mechanical allodynia and/or to gp120-induced increases in TNF and
      IL-1. An i.t. anti-rat IL-6 neutralizing antibody was used to block IL-6 actions
      upon its release by i.t. gp120. This IL-6 blockade abolished gp120-induced
      mechanical allodynia. While the literature predominantly documents the cascade of
      pro-inflammatory cytokines as beginning with TNF, followed by the stimulation of
      IL-1, and finally TNF plus IL-1 stimulating the release of IL-6, the present
      findings indicate that a blockade of IL-6 inhibits the gp120-induced elevations
      of TNF, IL-1, and IL-6 mRNA in dorsal spinal cord, elevation of IL-1 protein in
      lumbar dorsal spinal cord, and TNF and IL-1 protein release into the surrounding
      lumbosacral cerebrospinal fluid. These results would suggest that IL-6 induces
      pain facilitation, and may do so in part by stimulating the production and
      release of other pro-inflammatory cytokines.

PMID- 17204395
TI  - Early cytokine expression in mouse sciatic nerve after chronic constriction nerve
      injury depends on calpain.
AB  - Nerve injury initiates Wallerian degeneration with subsequent alterations of
      cytokine expression contributing to neuropathic pain. To investigate the very
      early temporal pattern of cytokine regulation we studied 140 mice of C57Bl/6J
      background after chronic constriction injury (CCI) of the right sciatic nerve and
      measured the relative mRNA expression of the pro-inflammatory cytokines tumor
      necrosis factor-alpha (TNF) and interleukin-1beta (IL-1beta) and of the anti
      inflammatory cytokines IL-4 and IL-10 with quantitative real-time polymerase
      chain reaction (qRT-PCR). The measurements were performed in ipsi- and
      contralateral sciatic nerves and dorsal root ganglia (DRG) 1, 3, 6, 9, 12, 24 h,
      and 3 and 7 days after CCI. We found an ipsilateral upregulation of TNF, IL-1beta
      and IL-10 mRNA levels as early as one hour after CCI. To investigate upstream
      regulatory mechanisms, we used inhibitors to the N-methyl-d-aspartate (NMDA)
      receptor ((+)-MK-801) and to calpain (MDL-28170). MDL-28170, but not (+)-MK-801
      inhibited TNF and IL-1beta upregulation one hour after CCI. This leads us to
      suggest that calpain is one of the earliest mediators of cytokine upregulation in
      injured peripheral nerves.

PMID- 17204396
TI  - Redox signalling in anchorage-dependent cell growth.
AB  - Current data have provided new perspectives concerning the regulation of non
      transformed cell proliferation in response to both soluble growth factors and to
      adhesive cues. Non-transformed cells are anchorage dependent for the execution of
      the mitotic program and cannot avoid the concomitant signals starting from
      mitogenic molecules, as growth factors, and adhesive agents belonging to
      extracellular matrix. Reactive oxygen species play a key role during both growth
      factor and integrin receptor signalling and these second messengers are
      recognised to have a synergistic function for anchorage-dependent growth
      signalling. Redox regulated proteins include protein tyrosine phosphatases and
      protein tyrosine kinases, although with opposite regulation of their enzymatic
      activity, and cytoskeletal proteins as beta-actin. In this review we support a
      role of ROS as key second messengers granting a proper executed mitosis for
      anchorage-dependent cells, through redox regulation of several downstream
      targets. Deregulation of these redox pathways may help to guide transformed cells
      to elude the native apoptotic response to abolishment of signals started by
      cell/ECM contact, sustaining ectopic anchorage-independent cancer cell growth.

PMID- 17204397
TI  - The validity of using patient self-report to assess psychotic symptoms in
      schizophrenia.
AB  - Brief, reliable and valid measures of psychosis can be very useful in both
      clinical practice and research, and for identifying unmet treatment needs in
      persons with schizophrenia. This study examines the concurrent validity and
      receiver operating characteristics of the psychosis scale of the Revised Behavior
      and Symptom Identification Scale (BASIS-R). The study was conducted with 71
      adults with schizophrenia who were randomly sampled from a large mental health
      clinic. Study participants at the West Los Angeles Veterans Healthcare Center
      were assessed using the BASIS-R, a subjective, self-report measure, and the UCLA
      Brief Psychiatric Rating Scale (BPRS), a clinician-rated measure administered by
      highly trained research staff. The psychosis scale of the BASIS-R shows good
      concurrent validity with the psychosis items on the BPRS. Using the BPRS as the
      gold standard for measuring psychosis, receiver operating characteristics suggest
      that both the weighted and unweighted versions of the BASIS-R psychosis scale
      adequately identify psychosis that is moderate or greater or severe. The
      performance of the two versions was similar. Unweighted scores are easier to
      calculate, and we therefore recommend cutoff scores based on the unweighted BASIS
      R. We identified a cutoff score of 0.5 to best detect moderate or greater
      psychosis, and a cutoff score of 1.0 to best detect severe or extremely severe
      psychosis. The BASIS-R has potential as an assessment tool and screening
      instrument in schizophrenia.

PMID- 17204398
TI  - Blunted serotonergic responsivity in neuroleptic-naive patients at first-episode
      of schizophrenia.
AB  - OBJECTIVE: To determine whether serotonergic responsivity, as assessed in
      platelets, is blunted in treatment-naive patients with first episode psychosis,
      similar to observations in chronic schizophrenia. METHODS: Serotonin (5-HT)
      amplified platelet aggregation was determined in 26 first-episode treatment-naive
      patients with psychosis (14 with schizophrenia, 12 with mood disorders with
      psychosis) and 16 matched healthy comparison subjects. Platelet aggregation was
      measured in fresh whole blood after stimulation with 5.0 microM adenosine
      diphosphate (ADP) alone and with the addition of 0.2 microg and 1.0 microg 5-HT.
      RESULTS: Healthy subjects showed expected robust increases in platelet
      aggregation (+106% and +146% at 0.2 microg and 1.0 microg 5-HT, respectively). By
      contrast, patients with schizophrenia showed almost no changes in aggregation
      (+6% and +3%), while patients with mood disorders showed intermediate increases
      (+59% and +66%). CONCLUSIONS: Blunted platelet serotonergic responsivity appears
      to be independent of treatment effects. To determine whether this is trait
      related factor will require prospective studies.

PMID- 17204399
TI  - Polymorphism of the IL-10 gene is associated with susceptibility to herpes zoster
      in Korea.

PMID- 17204400
TI  - Chemosensitisation of drug-resistant and drug-sensitive yeast cells to
      antifungals.
AB  - Multidrug resistance in yeast results from overexpression of genes encoding drug
      efflux transporters owing to gain-of-function mutations in transcription factors
      regulating their expression. We have screened a library of synthetic compounds
      for modulators of drug resistance using the multidrug-resistant Saccharomyces
      cerevisiae pdr3-9 mutant strain. One of the compounds, 7-chlorotetrazolo[5,1
      c]benzo[1,2,4]triazine (CTBT), displayed weak antifungal activity and strongly
      inhibited the growth of yeast cells in combination with subinhibitory
      concentrations of other antifungals with a different mode of action. Biological
      activity of CTBT was demonstrated in Saccharomyces, Kluyveromyces and Candida
      yeast species grown on solid and in liquid media. The chemosensitising effect of
      CTBT, manifested as increased antifungal activity of fluconazole, was
      demonstrated in yeast mutant strains with deleted genes encoding the major
      multidrug resistance transcription factors Yap1p, Pdr1p and Pdr3p as well as the
      drug efflux pumps Pdr5p and Snq2p in S. cerevisiae or their counterparts in
      Candida albicans and Candida glabrata, named Cdr1p and Mdr1p, respectively.
      Importantly, CTBT also increased the sensitivity to fluconazole in multidrug
      resistant cells overexpressing the efflux pumps. Yeast cells grown in the
      presence of subinhibitory concentrations of CTBT exhibited an altered sterol
      composition and a slightly enhanced accumulation of Rhodamine 6G, which suggests
      that the plasma membrane plays a role in sensitisation. This novel
      chemosensitisation by CTBT that can overcome multidrug resistance in yeast may
      prove useful in combined treatment of infections caused by drug-resistant fungal
      pathogens.

PMID- 17204401
TI  - The secret life of the multilocus sequence type.
AB  - Such are the challenges, and the potential, presented by complete genome
      sequences that the eventual erosion of the boundaries between biochemistry,
      ecology, bioinformatics, population biology, epidemiology and medical
      microbiology will perhaps be the most profound legacy of the genomics revolution.
      The development of nucleotide sequence-based typing schemes (multilocus sequence
      typing (MLST)) represents a similar synthesis, for this technique both matches
      the practical requirements for a highly portable standard for strain
      characterisation whilst also being firmly grounded in the population biology
      principles of multilocus enzyme electrophoresis (MLEE). Contrary to recent claims
      that population biology analyses of public health-oriented MLST data 'obscures
      its utility in applied microbiology' [Maiden MC. Multilocus sequence typing of
      bacteria. Annu Rev Microbiol 2006;60:561-88.], we argue that such an emphasis is
      essential for full interpretation of the data. Here we note a pertinent case in
      point; how a consideration of the rates of genetic recombination can help to
      explain why MLST data tend to correlate with virulence properties in some species
      (Neisseria meningitidis) but not in others (Staphylococcus aureus). We also
      discuss how the argument applies to the identification of recently emerged
      methicillin-resistant S. aureus (MRSA) clones using MLST. We conclude with a
      speculative rationale for promoting the 'clonal complexes' of S. aureus to
      species status.

PMID- 17204402
TI  - Evaluation of an intracellular pharmacokinetic in vitro infection model as a tool
      to assess tuberculosis therapy.
AB  - In vitro intracellular infection models have been used to evaluate drug therapy
      against Mycobacterium tuberculosis; however, they do not simulate human
      pharmacokinetics. This study demonstrates the intracellular and extracellular
      killing activity of antimycobacterial drugs in a pharmacokinetic intracellular in
      vitro model. The pharmacokinetic parameters of levofloxacin, rifampicin and
      isoniazid were controlled in the central chamber; drug passively diffused into
      the cell culture inserts and then into the macrophages. In the pharmacokinetic
      model, the rates of killing observed were faster than other in vitro methods and
      allowed for a higher initial inoculum to be utilised. The pharmacokinetic model
      more closely mimics in vivo conditions than other in vitro systems and is a new
      instrument for evaluating the activity of antimycobacterial agents.

PMID- 17204403
TI  - Bactericidal activity of daptomycin, vancomycin, teicoplanin and linezolid
      against Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium
      using human peak free serum drug concentrations.
AB  - The bactericidal activities of daptomycin, vancomycin, teicoplanin and linezolid
      at human peak free serum concentrations (C(max,free)) were determined against
      Staphylococcus aureus (one methicillin-susceptible and two methicillin-resistant
      strains), Enterococcus faecalis and Enterococcus faecium (one vancomycin
      susceptible and one vancomycin-resistant strain of each). Daptomycin was rapidly
      bactericidal against 7/7 strains at C(max,free) of 22.0 mg/L (corresponding to
      63% protein binding) and against 3/7 strains at 4.8 mg/L (corresponding to 92%
      protein binding). Vancomycin (18.0 mg/L) was bactericidal against only two
      strains. Both teicoplanin (4.5 mg/L) and linezolid (10.4 mg/L) were consistently
      bacteriostatic. Daptomycin is a useful option for the treatment of Gram-positive
      infections owing to its strong bactericidal activity.

PMID- 17204404
TI  - Ethical aspects for veterinarians regarding antimicrobial drug use in Italy.
AB  - Antimicrobial drugs are used in the treatment and control of many types of
      infections in a wide variety of animal species. As more antibiotics were
      discovered and introduced to veterinary clinical practice, it became clear that
      choice among rational agents needed to be guided by the agreement of antibiotic
      policies or 'ethical' measures. Prudent use of antimicrobial drugs is an integral
      part of good veterinary practice; it is an attitude to maximise therapeutic
      efficacy and to minimise selection of resistant microorganisms. This paper
      presents an overview of the judicious use of antimicrobial agents in animals,
      with particular emphasis on ethical aspects.

PMID- 17204405
TI  - parE mutations in Streptococcus pneumoniae may reduce bactericidal activity of
      respiratory fluoroquinolones.

PMID- 17204406
TI  - Reduced imipenem susceptibility in Klebsiella pneumoniae clinical isolates with
      plasmid-mediated CMY-2 and DHA-1 beta-lactamases co-mediated by porin loss.
AB  - We investigated the resistance mechanisms and clonality among 42 imipenem-non
      susceptible Klebsiella pneumoniae isolated at a tertiary care hospital in Korea.
      Two isolates had bla(VIM-2) alleles, whereas bla(CMY-2)- and bla(DHA-1)-like
      alleles were detected in 24 and 16 isolates, respectively, with these enzymes
      confirmed by sequencing for representative isolates. Transfer of bla(CMY-2) and
      bla(DHA-1) was achieved by conjugation. Addition of 300 mg/L 3-aminophenylboronic
      acid (APB) reduced the minimum inhibitory concentration for 90% of the organisms
      (MIC(90)) of imipenem and meropenem eight- and four-fold, respectively, for the
      bla(CMY-2)- and bla(DHA-1)-positive isolates, confirming the role of these
      enzymes in resistance. SDS-PAGE of outer membrane proteins for representative
      isolates showed lack or greatly diminished expression of OmpK35 and OmpK36
      porins. Pulsed-field gel electrophoresis of XbaI-restricted genomic DNA revealed
      two closely related clusters among 23 bla(CMY-2)-positive isolates, whereas those
      with bla(DHA-1) were more heterogeneous. In conclusion, reduced imipenem
      susceptibility among K. pneumoniae at this Korean hospital was largely co
      mediated by production of plasmid-mediated AmpC beta-lactamases along with lack
      or greatly diminished expression of OmpK35 and OmpK36 porins.

PMID- 17204407
TI  - Linezolid for the treatment of adults with bone and joint infections.
AB  - We reviewed the available evidence regarding the effectiveness and safety of
      linezolid administration for the treatment of patients with orthopaedic
      infections due to multidrug-resistant Gram-positive cocci. Although the reports
      published to date include promising results for the use of linezolid for bone and
      joint infections, controlled studies will be needed to reach safe conclusions.
      Attention should be paid to adverse effects that may be related to linezolid
      administration, especially bone marrow suppression with prolonged administration
      of the antibiotic. In addition, early identification of linezolid-induced
      peripheral neuropathy is necessary because this may be an irreversible event.

PMID- 17204408
TI  - Effects of genetic backgrounds on hyperbilirubinemia in radixin-deficient mice
      due to different expression levels of Mrp3.
AB  - ERM (ezrin/radixin/moesin) proteins are organizers of apical actin cortical layer
      in general. We previously reported that the knockout of radixin resulted in Rdx(
      /-) mice with displacement/loss of the canalicular transporter Mrp2, giving rise
      to Dubin-Johnson syndrome-like conjugated hyperbilirubinemia in the mixed genetic
      background (C57BL/6-129/Sv) (Kikuchi, et al. (2002) Nature Genetics 31, 320-325).
      However, when these mice were kept under mixed genetic background for years (late
      mixed backgrounds; LMB), the conjugated hyperbilirubinemia gradually became
      inconspicuous, while evidence of liver injury increased. We examined the effect
      of genetic background by backcrossing LMB Rdx(-/-) mice to C57BL/6 and 129/Sv
      wild type mice with the result that the Rdx(-/-) congenic mice regained
      hyperbilirubinemia with reduced hepatocellular damage. As revealed by
      immunofluorescence and western blots, the localization/expression of apical
      transporters, Mrp2, CD26, P-gps, and Bsep were not influenced by backcrossing,
      though those of a basolateral transporter, Mrp3, were strikingly increased by
      backcrossing.

PMID- 17204409
TI  - Drug permeability across a phospholipid vesicle based barrier: 3.
      Characterization of drug-membrane interactions and the effect of agitation on the
      barrier integrity and on the permeability.
AB  - Recently, we reported on the development and structural characterization of a
      phospholipid vesicle based barrier useful for medium throughput screening of
      passive drug permeability. Here, we investigate the physical and functional
      integrity of the phospholipid vesicle based barriers to agitation by stirring or
      shaking, and whether agitation affects drug permeability of sulpiride, metoprolol
      and testosterone. In addition, three drugs (caffeine, naproxen and
      sulphasalazine) which were shown in a previous study to affect the electrical
      resistance of the barriers, were investigated for their influence on the
      permeability of a simultaneously applied hydrophilic marker (calcein), and on the
      thermotropic phase transition of the phospholipid bilayers using differential
      scanning calorimetry (DSC). Electrical resistance measurements indicated that the
      barriers should withstand shaking speeds up to 150rpm without losing their
      integrity, but significant release of phospholipids from the membrane barriers to
      the donor and acceptor chambers was observed under agitation >or=150rpm. When
      using agitation up to 100rpm no increase in permeability was observed for
      sulpiride, metoprolol and testosterone. The phospholipid vesicle-based barrier
      thus differ from other permeability models in that agitation does not lead to an
      increase in permeability, not even for highly lipophilic drugs such as
      testosterone. This is explained by the different morphology of the vesicle-based
      barrier which is containing a 100microm thick layer of mostly aqueous
      compartments immobilised within a matrix of phospholipids vesicles.
      Sulphasalazine and naproxen were shown to decrease the electrical resistance and
      increase the permeability of the hydrophilic marker calcein. The DSC experiments
      showed that these two drugs probably interact with the head groups of the
      phospholipids. In contrast, caffeine gave an increase in electrical resistance
      and a decrease in permeability of calcein. From the DSC experiments no signs of
      interaction of caffeine with the phospholipid bilayer could be observed.

PMID- 17204410
TI  - The use of a new hydrophilic polymer, Kollicoat IR, in the formulation of solid
      dispersions of Itraconazole.
AB  - Kollicoat IR, a new pharmaceutical excipient developed as a coating polymer for
      instant release tablets, was evaluated as a carrier in solid dispersions of
      Itraconazole. The solid dispersions were prepared by hot stage extrusion.
      Modulated temperature differential scanning calorimetry and X-ray powder
      diffraction were used to evaluate the miscibility of the drug and the carrier.
      The pharmaceutical performance was evaluated by dissolution experiments,
      performed in simulated gastric fluid without pepsin (SGF(sp)). In the X-ray
      diffractograms no Itraconazole peaks were visible; the polymer on the other hand
      appeared to be semi-crystalline. Moreover, its crystallinity increased during the
      extrusion process due to exposure to heat and shear forces. Modulated temperature
      differential scanning calorimetry analysis showed that the drug and the polymer
      formed a two phase system. Separate clusters of glassy Itraconazole were present
      for drug loads of 40% or higher, indicating further phase separation. Dissolution
      measurements demonstrated a significantly increased dissolution rate for the
      solid dispersions compared to physical mixtures. Interestingly the physical
      mixture made up of glassy Itraconazole and Kollicoat IR (20/80, w/w) showed a
      dissolution rate and maximum that was much higher than that of the physical
      mixture made up of crystalline Itraconazole and that of pure glassy Itraconazole.
      The results of this study show that Kollicoat IR is a promising excipient for the
      formulation of solid dispersions of Itraconazole prepared by hot stage extrusion.

PMID- 17204411
TI  - Protein kinase C inhibition attenuates hypochlorite-induced acute lung injury.
AB  - Neutrophil-derived oxidative stress plays a crucial role in acute lung injury.
      Hypochlorite/hypochlorous acid (HOCl) is a major oxidant of neutrophils. Protein
      kinase C (PKC) may be an appropriate target for HOCl due to its functionally
      important thiols. This study investigates the role of PKC in HOCl-induced acute
      lung injury. Isolated lung preparations were from 30 rabbits. HOCl (1000 nmol
      min(-1)) or buffer (control) were infused into isolated rabbit lungs. Pulmonary
      artery pressure (PAP [Torr]) and lung weight were continuously measured.
      Capillary filtration coefficient (K(f,c)), was measured at baseline and at 30,
      60, 90 min. Experiments were terminated at 105 min or when fluid retention
      exceeded 50 g. The non-selective protein kinase inhibitor staurosporin (100 nM)
      or the selective PKC inhibitor bisindolylmaleimide I (GF109203X, 10nM) were added
      to the perfusate 5 min prior to the start of the experiments. Staurosporin
      completely prevented the HOCl-induced increase in PAP (no change versus
      DeltaPAP(max) 5.2+/-0.78) but did not influence the increase in vascular
      permeability. GF109203X delayed the HOCl-induced increase in PAP and vascular
      permeability. PAP(max) was observed significantly later in the HOCl-GF109203X
      group (84.4+/-4.0 min) in comparison with the HOCl group (52.1+/-3.5 min).
      Termination of the experiments due to edema formation occurred significantly
      later in experiments with GF109203X (91.8+/-1.9 versus 79.2+/-4.1 min). Protein
      kinases are involved in HOCl-induced acute lung injury. Specifically PKC
      inhibition delayed HOCl-induced increases in PAP and vascular permeability.

PMID- 17204412
TI  - Electrochemical quartz crystal impedance study on the overoxidation of
      polypyrrole-carbon nanotubes composite film for amperometric detection of
      dopamine.
AB  - The electrochemical quartz crystal impedance (EQCI) method was used to study the
      overoxidation of polypyrrole (PPy)-multiwalled carbon nanotubes (MWCNT)
      nanocomposite film in neutral and alkaline solutions. The values of molar mass
      per electron transferred (M/n) obtained during the overoxidation of PPy in 0.10
      mol L(-1) Na(2)SO(4) and 0.20 mol L(-1) NaOH aqueous solutions were estimated to
      be ca. 17 and 22 g mol(-1), respectively, suggesting the nucleophilic attack of
      solution OH(-) to the pyrrole units during the overoxidation, and the possible
      partial formation of carboxylic groups after the overoxidation in the NaOH
      solution. Also, the overoxidized PPy-MWCNT composite film prepared in the NaOH
      solution showed a notably larger affinity to dopamine (DA) dissolved in a neutral
      phosphate buffer than that prepared in the Na(2)SO(4) solution. The modification
      of the overoxidized nanocomposite film improved substantially the sensitivity for
      DA assay in a neutral phosphate buffer, as compared with the modification of
      overoxidized PPy or MWCNT alone. At a -6 kHz (201-nm thickness) nanocomposite
      film prepared in a polymerization bath containing 1.0 mg mL(-1) MWCNT and
      overoxidized in 0.20 mol L(-1) aqueous NaOH, the peak current response from
      differential pulse voltammetric assay of DA was linear with DA concentration from
      4.0 x 10(-8) to 1.4 x 10(-6) mol L(-1), with a lower limit of detection of 1.7
      nmol L(-1), good anti-interferent ability, as well as good stability and
      reproducibility.

PMID- 17204413
TI  - Determination of microsatellite repeats in the human thyroid peroxidase (TPOX)
      gene using an automated gene analysis system with nanoscale engineered
      biomagnetite.
AB  - The number of repeat in the microsatellite region (AATG)(5-14) of the human
      thyroid peroxidase gene (TOPX) was determined using an automated DNA analysis
      system with nano-scale engineered biomagnetite. Thermal melting curve analysis of
      DNA duplexes on biomagnetite indicated that shorter repeat sequences (less than 9
      repeats) were easily discriminated. However, it was difficult to determine the
      number of repeats at more than nine. In order to improve the selectivity of this
      method for the longer repeats, a "double probe hybridization assay" was performed
      in which an intermediate probe was used to replace a target repeat sequence
      having more than 9 repeats with a shorter sequence possessing less than 9
      repeats. Thermal probe melting curve analyses and Tm determination confirmed that
      the target with 10 repeats was converted to 5 repeats, 11 repeats converted to 4
      and 12 to 3, respectively. Furthermore, rapid determination of repeat numbers was
      possible by measuring fluorescence intensities obtained by probe dissociation at
      56 and 66 degrees C, and 40, 60 and 80 degrees C for signal normalization.

PMID- 17204414
TI  - Molecular imaging in heart failure.
AB  - Heart failure (HF), a heterogeneous syndrome of epidemic proportions, is
      increasingly defined by its underlying molecular and genomic alterations.
      Molecular cardiac imaging has emerged as a complementary discipline that has
      improved the understanding of the pathophysiologic principles governing
      experimental HF and has a potential to revolutionize assessment and management of
      HF in humans.

PMID- 17204415
TI  - Visual circuit development in Drosophila.
AB  - Fly visual circuits are organized into lattice-like arrays and layers. Recent
      genetic studies have provided insights into how these reiterated structures are
      assembled through stepwise processes and how precise connections are established
      during development. Afferent-derived morphogens, such as Hedgehog, play a key
      role in organizing the overall structure by inducing and recruiting target
      neurons and glia. In turn, the target-derived ligand DWnt4 guides Frizzled2
      expressing photoreceptor afferents to their proper destination. Photoreceptor
      afferents select specific synaptic targets by forming adhesive interactions and
      regulating actin cytoskeleton in growth cones. Target specificity is probably
      achieved by restricting the expression of adhesive molecules, such as Capricious,
      to appropriate presynaptic and postsynaptic partners, and by differentially
      regulating the function of broadly expressed adhesive molecules such as N
      cadherin.

PMID- 17204416
TI  - The effects of Vitamin D metabolites on expression of genes for calcium
      transporters in human duodenum.
AB  - The role of Vitamin D in the regulation of calcium absorption in the intestine is
      well recognized but the mechanisms of the effects on human genes are surprisingly
      poorly understood. We have determined the expression of transcripts of the apical
      membrane calcium transporter TRPV6, the cytoplasmic calcium binding protein
      calbindin-D9k, the basolateral plasma membrane Ca(2+)-ATPase (PMCA1) and the
      Vitamin D receptor (VDR) in normal endoscopic duodenal mucosal biopsies using
      quantitative real-time RT-PCR and related baseline expression to Vitamin D
      metabolites. TRPV6 transcript levels have been shown to be significantly
      correlated with serum 1,25(OH)(2)D levels in men, but not overall in women, where
      negative effects of age predominate. TRPV6 and VDR expression were significantly
      related in both men and women, but were significantly lower in older women.
      Associations with bone mineral density and fractional calcium absorption were
      also studied. In a second series of subjects, duodenal biopsies were incubated in
      organ culture for 6h with Vitamin D metabolites. TRPV6 expression was
      significantly increased by 1,25(OH)(2)D(3) (10(-9)mol/l) as was PMCA1 to a much
      smaller extent. TRPV6 expression also increased with 25(OH)D(3). CYP27B1
      expression was found in all samples, and CYP24 transcripts were detected after
      incubation with 1,25(OH)(2)D(3) or 25(OH)D(3).

PMID- 17204417
TI  - Extracellular calcium is a direct effecter of VDR levels in proximal tubule
      epithelial cells that counter-balances effects of PTH on renal Vitamin D
      metabolism.
AB  - In renal proximal tubules, VDR is transiently decreased by parathyroid hormone
      (PTH) during times of hypocalcemia and returns to normal levels with the rise in
      serum calcium (Ca). In this study we tested the hypothesis that elevated
      extracellular Ca induces VDR in a human renal proximal cell line (HK-2G) stably
      expressing PTH receptor type I. Exposure of HK-2G cells to increasing Ca
      concentration, up to 3mM, induced the expression of VDR. The increase in VDR
      occurred within 1h and was sustained over 24h. The increase in VDR was also dose
      dependently increased using 20-100 nM gadolinium, suggesting the induction of VDR
      is regulated via the extracellular Ca sensing receptor (CaSR) with is naturally
      expressed in HK-2G cells. In conclusion, an extracellular Ca concentration in the
      physiological range is capable of direct increase of renal proximal VDR
      expression, and the induction mechanism represents a strategy the body may use to
      counterbalance effects of PTH on renal Vitamin D metabolism.

PMID- 17204418
TI  - Sunlight, skin cancer and vitamin D: What are the conclusions of recent findings
      that protection against solar ultraviolet (UV) radiation causes 25-hydroxyvitamin
      D deficiency in solid organ-transplant recipients, xeroderma pigmentosum, and
      other risk groups?
AB  - A connection between vitamin D deficiency and severe health problems including
      various types of cancer has been demonstrated. We have shown that patients that
      have to protect themselves against solar UV radiation for medical reasons,
      including patients with xeroderma pigmentosum (XP), basal cell nevus syndrome
      (BCNS), lupus erythematodes (LE) or transplant recipients, are at risk to develop
      vitamin D deficiency. We conclude that 25-hydroxyvitamin D serum levels as a
      measure of vitamin D status have to be analyzed in patients that have to protect
      themselves against solar UV radiation for medical reasons. Suboptimal vitamin D
      status has to be substituted (e.g. via oral treatment) to protect against serious
      vitamin D deficiency-related health problems without increasing the risk to
      develop solar UV-induced skin cancer. Our finding that protection against solar
      UV radiation causes vitamin D deficiency underlines the need for re-defining
      dermatological recommendations for solar UV protection in skin cancer prevention
      programs.

PMID- 17204419
TI  - Processing of Rosa rubiginosa: extraction of oil and antioxidant substances.
AB  - In this work, a study about the effect of various operational conditions on the
      quantity of oil and soluble solids capable of being extracted from rosa mosqueta
      rosehip seeds is undertaken. Both the particle sizes assayed (0.6mm, 0.6-1mm, and
      1-2mm) and the solvent-to-solid ratios (15:1, 25:1, and 50:1) showed a remarkable
      influence on the extraction efficiency. Extracted substances obtained by using
      the minor particle size or the maximum solvent-to-solid ratio doubled, at least,
      those attained by working under any other conditions. A major weight of kinetics
      upon equilibrium factors can be inferred from the short extraction times and high
      effective diffusivity values (being the lower one 1.97x10(-11)m(2)s(-1)) assessed
      for any condition. The antioxidant power of extracts was evaluated by ability to
      scavenge the DPPH radical. Results noteworthy depended on the solvent used to
      extract; whilst an approximately 80% DPPH inhibition percentage was reached in
      ethanol extracts, values of 52.2% or 41% were found in methanol and aqueous
      extracts, respectively. Even so, antioxidant capacity of Rosa rubiginosa extracts
      was much higher than that reported for other agricultural matrixes.

PMID- 17204420
TI  - Characterization of vine shoots, cotton stalks, Leucaena leucocephala and
      Chamaecytisus proliferus, and of their ethyleneglycol pulps.
AB  - We characterized vine shoots, cotton stalks, Leucaena leucocephala and
      Chamaecytisus proliferus as pulping raw materials and found C. proliferus and
      cotton stalks to be the best for the intended purpose on the grounds of their
      increased contents in holocellulose (79.73% and 72.86%) and alpha-cellulose
      (45.37% and 58.48%), and their decreased contents in ethanol-benzene extractables
      (2.64% and 1.42%), hot water solubles (2.79% and 3.33%) and 1% soda solubles
      (16.67% and 20.34%). These properties resulted in increased pulp yields and hence
      in efficient use of these two types of raw material. The previous raw materials
      were pulped by using an ethyleneglycol concentration of 65% at 180 degrees C for
      75min, followed by beating at 1500 revolutions in a PFI refiner. The paper sheets
      obtained were characterized and those from C. proliferus found to be the best
      overall as they exhibited an increased breaking length (4644m), stretch (2.87%),
      burst index (2.46kN/g) tear index (0.33mNm(2)/g) and brightness (49.92% ISO); in
      addition C. proliferus pulp was obtained with a high-yield (62.88%). On the other
      hand, vine shoots provided the poorest results among the studied raw materials.

PMID- 17204421
TI  - Compost-based growing media: influence on growth and nutrient use of bedding
      plants.
AB  - The agronomic performance and the mineral composition and trace element content
      in Begonia semperflorens "Bellavista F1", Mimulus "Magic x hybridus", Salvia
      splendens "maestro", and Tagete patula xerecta "Zenith Lemon Yellow", were tested
      by growing the plants on substrates of white peat and 25-50-75-100% green waste
      and sewage sludge (80%+20%v/v) compost (CP). A commercial peat medium of black
      and white peat (2:1v/v) was used as control. At flowering, the agronomic
      parameters were compared by ANOVA and plant nutritional status was compared by
      vector analysis. Substrate-species interactions (P<0.001) were evident for all
      measured parameters. In the 25% CP medium all the species showed an increase or
      preservation of the studied agronomic parameters. Begonia grown in 25% CP, showed
      the highest dry weight (DW) and number of flowers. Other treatments were
      comparable to the control. Mimulus and Salvia showed the highest DW in the 25-50%
      CP. Mimulus, after a DW increase up to 50% CP, showed the steepest reduction as
      the CP increased further. Tagete showed no differences in DW up to 50% CP, or in
      flower number up to 25% CP, compared to the control. The additional increases of
      CP in the medium showed a DW decrease similar to that of Salvia. Vector analysis
      showed the use of compost mainly induced a decrease of P concentration in
      tissues, except for Begonia which remained unchanged. Plant tissues showed a
      general P reduction due to a dilution effect in the low compost mixtures (25-50%)
      and a deficiency in the higher CP mixtures. In contrast, an increase of Mg in the
      aboveground tissues of all species was detectable as compost usage increased,
      with the exception of Salvia which suffered a Mg deficiency. Vector analysis also
      highlighted a Ni and partial Fe deficiency in Tagete and Salvia.

PMID- 17204422
TI  - Biodegradation of Reactive blue-25 by Aspergillus ochraceus NCIM-1146.
AB  - The present study dealt with the decolorization and degradation of textile dye
      Reactive blue-25 (0.1gl(-1)) by mycelium of Aspergillus ochraceus NCIM-1146.
      Spectrophotometric and visual examinations showed that the decolorization was
      through fungal adsorption, followed by degradation. Shaking condition was found
      to be better for complete and faster adsorption (7h) and decolorization (20 days)
      of dye Reactive blue-25 (100mgl(-1)) as compared to static condition. Presence of
      glucose in medium showed faster adsorption (4h) and decolorization of dye from
      bound (7 days) mycelium. FTIR and GCMS analysis study revealed biodegradation of
      Reactive blue-25 into two metabolites phthalimide and di-isobutyl phthalate.

PMID- 17204423
TI  - Review paper on current technologies for decolourisation of textile wastewaters:
      perspectives for anaerobic biotechnology.
AB  - Dyes are natural and xenobiotic compounds that make the world more beautiful
      through coloured substances. However, the release of coloured wastewaters
      represents a serious environmental problem and a public health concern. Colour
      removal, especially from textile wastewaters, has been a big challenge over the
      last decades, and up to now there is no single and economically attractive
      treatment that can effectively decolourise dyes. In the passed years, notable
      achievements were made in the use of biotechnological applications to textile
      wastewaters not only for colour removal but also for the complete mineralization
      of dyes. Different microorganisms such as aerobic and anaerobic bacteria, fungi
      and actinomycetes have been found to catalyse dye decolourisation. Moreover,
      promising results were obtained in accelerating dye decolourisation by adding
      mediating compounds and/or changing process conditions to high temperatures. This
      paper provides a critical review on the current technologies available for
      decolourisation of textile wastewaters and it suggests effective and economically
      attractive alternatives.

PMID- 17204424
TI  - The impact of an evidence-based practice education program on the role of oral
      care in the prevention of ventilator-associated pneumonia.
AB  - BACKGROUND: Despite strong evidence in the literature on the role of oral care in
      the prevention of ventilator-associated pneumonia (VAP), nurses continue to view
      oral care as a comfort measure with low priority and utilise foam swabs rather
      than toothbrushes. Although an evidence-based oral care protocol existed and best
      practice oral care tools were available, the VAP rates had not significantly
      decreased even though nurses reported providing oral care. OBJECTIVES: The aim of
      the study was to determine if an evidence-based practice (EBP) educational
      programme would improve the quality of oral care delivered to mechanically
      ventilated patients; thereby, reducing the VAP rate. RESULTS: Improvement in oral
      health was demonstrated by a decrease in median scores on the Oral Assessment
      Guide (pre (11.0), post (9.0)). A t-test analysis revealed a statistically
      significant difference (p=0.0002). The frequency of oral care documentation also
      improved as demonstrated by a positive shift to the more frequent timeframes. The
      VAP rates have decreased by 50% following the EBP education intervention.
      CONCLUSIONS: The implementation of an EBP educational programme focused on
      patient outcome rather than a task to be performed improved the quality of oral
      care delivered by the nursing staff.

PMID- 17204425
TI  - Biological profile of new apoptotic agents based on 2,4-pyrido[2,3-d]pyrimidine
      derivatives.
AB  - In order to obtain less toxic antitumoral compounds we have looked for novel
      compounds with anticancer activity based on proapoptotic mechanisms. The
      compounds studied in this work are derivatives of bicyclic aromatic systems like
      pyrido[2,3-d]pyrimidines. The potential antitumoral activity of the compounds was
      evaluated in vitro by examining their cytotoxic effects against human breast,
      colon, and bladder cancer lines (MD-MBA-231, HT-29, and T-24). The data indicate
      that HC-6 is a potent anticancer drug showing dose-dependent cytostatic and
      proapoptotic effects through activation of two different signaling pathways
      namely a pathway leading to cell cycle arrest and a transcription-independent
      route leading to rapid apoptosis.

PMID- 17204426
TI  - Antidepressant-like profile of action of two 4-amine derivatives of 10,11-dihydro
      5H-dibenzo [a,d] cycloheptane in mice evaluated in the forced swimming test.
AB  - This study investigated the antidepressant-like effect of 4-amine derivatives of
      10,11-dihydro-5H-dibenzo-alkylamine-cycloheptane, 4-amine (3-N,N
      dimethylpropylamine)-10,11-dihydro-5H-dibenzo[a,d]cycloheptane-5-one (ADDCH1) and
      1,2,3,4,8,9-hexahydro-dibenzocyclohepta[4,4a,5-ef]1,4-diazepin (ADDCH2), in a
      validated experimental model of depression, the forced swimming test (FST) in
      mice. Female adult mice were sub-chronically (three doses in 24 h) or repeatedly
      (once a day for 10 days) treated with either of the compounds and evaluated in
      the FST. The sub-chronic treatment promoted a dose-dependent reduction in the
      immobility time in the FST with the doses of 50 mg/kg (ADDCH1) and 30 mg/kg
      (ADDCH2) ip being the most effective (33% and 37% of reduction, respectively). A
      similar profile of action was observed in the animals repeatedly treated with
      ADDCH1 50 mg/kg or ADDCH2 30 mg/kg ip (for 10 days) and there was no sign of
      motor impairment or locomotor activation as evaluated in the rota-rod and open
      field tests, respectively. These findings suggest that these amine derivatives of
      the system dibenzocycloheptane have an antidepressant-like action which could be
      of clinical interest and, therefore, deserves further investigation. In addition,
      putative underlying mechanisms of action are discussed.

PMID- 17204427
TI  - Comparative 11A structure of two molluscan hemocyanins from 3D cryo-electron
      microscopy.
AB  - Hemocyanins are giant extracellular proteins that transport oxygen in the
      hemolymph of many molluscs. Molluscan hemocyanins are cylindrical decamers or
      didecamers of a 350-400 kDa subunit that contains seven or eight different
      covalently linked globular functional units (FUs), arranged in a linear manner.
      Each FU carries a single copper active site and reversibly binds one dioxygen
      molecule. As a consequence, the decamer can carry up to 70 or 80 O(2) molecules.
      Although complete sequence information is now available from several molluscan
      hemocyanins, many details of the quaternary structure are still unclear,
      including the topology of the 10 subunits within the decamer. Here we show 3D
      reconstructions from cryo-electron micrographs of the hemocyanin decamer of
      Nautilus pompilius (Cephalopoda) and Haliotis tuberculata (Gastropoda) at a
      resolution of 11A (FSC(1/2-bit) criterion). The wall structure of both
      hemocyanins is very similar and shows, as in previous reconstructions, three
      tiers with 20 functional units each that encircle the cylinder wall, and the 10
      oblique minor and major wall grooves. However, the six types of wall FUs of the
      polypeptide subunit, termed a-b-c-d-e-f, are now for the first time individually
      discernable by their specific orientation, shape, and connections. Also, the
      internal collar complex of the decamers shows superior resolution which, in this
      case, reveals striking differences between the two hemocyanins. The five arcs (FU
      g pairs) of the central collar (in both hemocyanins) and the five slabs (FU-h
      pairs) of the peripheral collar (only present in Haliotis hemocyanin), as well as
      their connections to the wall and to each other are now more clearly defined. The
      arc is attached to the wall through a feature termed the anchor, a previously
      undescribed structural element of the hemocyanin wall.

PMID- 17204428
TI  - Influence of Coulombic repulsion on the dissociation pathways and energetics of
      multiprotein complexes in the gas phase.
AB  - Thermal dissociation experiments, implemented with blackbody infrared radiative
      dissociation and Fourier-transform ion cyclotron resonance mass spectrometry, are
      performed on gaseous protonated and deprotonated ions of the homopentameric B
      subunits of Shiga toxin 1 (Stx1 B5) and Shiga toxin 2 (Stx2 B5) and the
      homotetramer streptavidin (S4). Dissociation of the gaseous, multisubunit
      complexes proceeds predominantly by the loss of a single subunit. Notably, the
      fractional partitioning of charge between the product ions, i.e., the leaving
      subunit and the resulting multimer, for a given complex is, within error,
      constant over the range of charge states investigated. The Arrhenius activation
      parameters (E(a), A) measured for the loss of subunit decrease with increasing
      charge state of the complex. However, the parameters for the protonated and
      deprotonated ions, with the same number of charges, are indistinguishable. The
      influence of the complex charge state on the dissociation pathways and the
      magnitude of the dissociation E(a) are modeled theoretically with the discrete
      charge droplet model (DCDM) and the protein structure model (PSM), wherein the
      structure of the subunits is considered. Importantly, the major subunit charge
      states observed experimentally for the Stx1 B5(n+/-) ions correspond to the
      minimum energy charge distribution predicted by DCDM and PSM assuming a late
      dissociative transition-state (TS); while for structurally-related Stx2 B5(n+)
      ions, the experimental charge distribution corresponds to an early TS. It is
      proposed that the lateness of the TS is related, in part, to the degree of
      unfolding of the leaving subunit, with Stx1 B being more unfolded than Stx2 B.
      PSM, incorporating significant subunit unfolding is necessary to account for the
      product ions observed for the S4(n+) ions. The contribution of Coulombic
      repulsion to the dissociation E(a) is quantified and the intrinsic activation
      energy is estimated for the first time.

PMID- 17204429
TI  - Proteomic profiling of a snake venom using high mass detection MALDI-TOF mass
      spectrometry.
AB  - Proteomic profiling involves identification and quantification of protein
      components in complex biological systems. Most of the mass profiling studies
      performed with matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOF MS) have been restricted to peptides and small proteins
      (<20 kDa) because the sensitivity of the standard ion detectors decreases with
      increasing ion mass. Here we perform a protein profiling study of the snake venom
      Sistrurus miliarius barbouri, comparing 2D gel electrophoresis and reversed-phase
      high-performance liquid chromatography (HPLC) with a high mass cryodetector MALDI
      TOF instrument (Macromizer), whose detector displays an uniform sensitivity with
      mass. Our results show that such MS approach can render superior analysis of
      protein complexity compared with that obtained with the electrophoretic and
      chromatographic approaches. The summation of ion impacts allows relative
      quantification of different proteins, and the number of ion counts correlates
      with the peak areas in the reversed-phase HPLC. Furthermore, the sensitivity
      reached with the high mass cryodetection MS technology clearly exceeds the
      detection limit of standard high-sensitivity staining methods.

PMID- 17204430
TI  - Fragmentation of leucine enkephalin as a function of laser fluence in a MALDI TOF
      TOF.
AB  - The effects of laser fluence on ion formation in MALDI were studied using a
      tandem TOF mass spectrometer with a Nd-YAG laser and alpha-cyano hydrocinnamic
      acid matrix. Leucine enkephalin ionization and fragmentation were followed as a
      function of laser fluence ranging from the threshold of ion formation to the
      maximum available, that is, about 280-930 mJ/mm2. The most notable finding was
      the appearance of immonium ions at fluence values close to threshold, increasing
      rapidly and then tapering in intensity with the appearance of typical backbone
      fragment ions. The data suggest the presence of two distinct environments for ion
      formation. One is associated with molecular desorption at low values of laser
      fluence that leads to extensive immonium ion formation. The second becomes
      dominant at higher fluences, is associated initially with backbone type
      fragments, but, at the highest values of fluence, progresses to immonium
      fragments. This second environment is suggestive of ion desorption from large
      pieces of material ablated from the surface. Arrhenius rate law considerations
      were used to estimate temperatures associated with the onset of these two
      processes.

PMID- 17204431
TI  - Cell death by incompatibility in the fungus Podospora.
AB  - Filamentous fungi are naturally able of somatic fusions. When cells of unlike
      genotype at specific het loci fuse, non-self recognition operates in the fusion
      cell and a cell death reaction termed cell death by incompatibility is triggered.
      In Podospora anserina cell death by incompatibility is characterized by a
      dramatic vacuolar enlargement, induction of autophagy and cell lysis. Autophagy
      contributes neither to vacuolar morphological changes nor to cell death but
      rather protects cells against death. Autophagy could be involved in selective
      elimination of pro-death signals. Vacuole collapse and cytoplasm acidification
      might be the cause of cell death by incompatibility.

PMID- 17204432
TI  - Magnetic resonance imaging of the visual system in vivo: transsynaptic
      illumination of V1 and V2 visual cortex.
AB  - Brain nuclei directly receiving retinal projections are readily labeled in
      magnetic resonance images following intraocular injection of manganese (Mn). To
      assess whether Mn in retinal ganglion cell axons can be transsynaptically
      delivered to visual cortex, mice that had previously received intraocular Mn
      injection were anesthetized with isoflurane, and T1-weighted data sets were
      acquired of the eyes and brain using a 7-T magnetic resonance imaging machine.
      Image intensity within contralateral brain structures was evaluated by assessing
      1) signal-to-noise ratios, 2) mean image intensity, and 3) mean image intensity
      normalized to facial muscle intensity. Image intensity was increased throughout
      the visual pathway including within contralateral visual cortex areas V1 and V2L.
      Mean normalized image intensity was greater by 53% in the ipsilateral optic nerve
      and by 31% and 28% in the contralateral lateral geniculate nucleus and superior
      colliculus, respectively (N=5, P<0.02, paired t test). In contralateral visual
      cortex areas V1 and V2L, image intensity was increased by 7.5% and 6.8%,
      respectively (P<0.02 for both, paired t test). Power analysis of the different
      evaluation methods yielded evidence of superior sensitivity using the
      normalization method. Reconstruction of the visual system based upon threshold
      analysis allowed simultaneous visualization of all portions of the major retinal
      projections to the brain. These results support use of high magnetic field MRI
      imaging and data normalization for in vivo quantitative analysis of the mouse
      brain visual system including visual cortex.

PMID- 17204433
TI  - Human brain activity associated with audiovisual perception and attention.
AB  - Coherent perception of objects in our environment often requires perceptual
      integration of auditory and visual information. Recent behavioral data suggest
      that audiovisual integration depends on attention. The current study investigated
      the neural basis of audiovisual integration using 3-Tesla functional magnetic
      resonance imaging (fMRI) in 12 healthy volunteers during attention to auditory or
      visual features, or audiovisual feature combinations of abstract stimuli
      (simultaneous harmonic sounds and colored circles). Audiovisual attention was
      found to modulate activity in the same frontal, temporal, parietal and occipital
      cortical regions as auditory and visual attention. In addition, attention to
      audiovisual feature combinations produced stronger activity in the superior
      temporal cortices than attention to only auditory or visual features. These
      modality-specific areas might be involved in attention-dependent perceptual
      binding of synchronous auditory and visual events into coherent audiovisual
      objects. Furthermore, the modality-specific temporal auditory and occipital
      visual cortical areas showed attention-related modulations during both auditory
      and visual attention tasks. This result supports the proposal that attention to
      stimuli in one modality can spread to encompass synchronously presented stimuli
      in another modality.

PMID- 17204434
TI  - Comparison of functional activity in the rat cervical spinal cord during alpha
      chloralose and halothane anesthesia.
AB  - Alpha-chloralose is commonly used during animal fMRI studies for anesthesia,
      however, recovery of animals is difficult, limiting experimental design. The use
      of a less invasive anesthetic would enable chronic experiments. The present study
      compares functional activity in the spinal cord of the alpha-chloralose and
      halothane-anesthetized rat. Functional MRI of the rat cervical spinal cord was
      performed on 6 alpha-chloralose and 6 halothane-anesthetized rats in a Bruker 7 T
      MR system during electrical stimulation of the right forepaw. Following imaging,
      four animals from each group were perfused and spinal cords removed for
      immunohistochemical analysis. Areas of c-fos expression were identified with
      immunofluorescent labeling to confirm the presence of neuronal activity.
      Functional activity and c-fos expression were observed predominantly between the
      fifth and seventh cervical spinal cord segments. Areas of fMRI activation in the
      spinal cord correspond well with spinal cord physiology. Areas of c-fos
      expression confirmed that neuronal activity was present in the regions of fMRI
      activity. The regions and amount of fMRI activity observed were similar for both
      anesthetics. Functional magnetic resonance imaging of the spinal cord can be
      achieved using both alpha-chloralose and halothane anesthesia in rats. We
      therefore suggest that halothane may be used as an anesthetic agent for chronic
      fMRI studies of the spinal cord.

PMID- 17204435
TI  - Levetiracetam monotherapy for children and adolescents with benign rolandic
      seizures.
AB  - To assess the efficacy, tolerability and safety of Levetiracetam (LEV) therapy,
      we identified 21 (15 male; 6 female) patients with a history of benign epilepsy
      with centrotemporal spikes (BECTS), with and without secondarily generalization
      in children and adolescents aged between 5.0 and 12.1 years. LEV was administered
      as a first drug (number of patients=9) or converted after previous treatment with
      other AEDs (number of patients=12). The patients were subdivided into two groups:
      "newly diagnosed" patients and "converted" patients. Patients were followed up
      for 12 months and all patients were able to continue on LEV treatment. At the end
      of follow-up (12 months), all patients were seizure free or showed a reduction of
      seizures >50%. LEV dosage ranged from 1000 to 2500mg/daily. Overall, 100% of
      patients completed the 12 months study, without any important side effect.
      Somnolence and irritability occurred in two (9.5%) patients. Our results support
      findings that LEV monotherapy is effective and well tolerated in children with
      BECTS. Prospective, large, long-term double-blind studies are needed to confirm
      these findings.

PMID- 17204436
TI  - Psychiatric disorders in temporal lobe epilepsy patients over the first year
      after surgical treatment.
AB  - OBJECTIVE: To evaluate the psychiatric disorders over a 1-year period in a group
      of TLE patients who underwent surgery. METHODS: Prospective, open study in a
      sample of 70 TLE patients. Psychiatric disorders' assessment was made before
      surgery, and at 1, 6 and 12 months after surgery, with the structured clinical
      diagnostic interview for DSM-IV axis I diagnoses (SCID). Presurgical psychiatric
      and neurological variables were compared with the outcomes of surgery and the
      course of psychiatric pathology over the follow-up through parametric and non
      parametric tests. RESULTS: Depression decreased from 17.2% before surgery to 4.3%
      at 12 months after surgery (chi(2)=5.41, d.f.=1, p=0.071), anxiety disorders
      decreased from 21.5% before surgery to 14.2% at 12 months after surgery
      (chi(2)=10.309, d.f.=1, p<0.005). Patients with no presurgical psychiatric
      condition had lower postsurgical rate of psychiatric disorders than those with
      psychiatric history (X(2)=9.87, gl=1, p< or =0.001), with psychiatric disorders
      in the presurgical evaluation (X(2)=12.02, gl=1, p< or =0.001), or with both
      conditions (chi(2)=15.28, d.f.=1, p<0.001). No association was found between
      psychiatric disorders and the outcomes after surgery. No association was found
      between the course of psychiatric disorders before and after surgery and
      neurological or neurosurgical variables. CONCLUSIONS: Surgery in TLE patients
      does not worsen the global psychopathological status. Presurgical psychiatric
      morbidity was found to be related to the presence of psychiatric disorders after
      surgery. Specific psychiatric assessment should be made before and after surgery.

PMID- 17204437
TI  - Osteophytes: relevance and biology.
AB  - OBJECTIVE: Osteophytes are common features of osteoarthritis. This review
      summarizes the current understanding of the clinical relevance and biology of
      osteophytes. METHOD: This review summarizes peer-reviewed articles published in
      the PubMed database before May 2006. In addition this review is supplemented with
      own data and theoretical considerations with regard to osteophyte formation.
      RESULTS: Osteophytes can contribute both to the functional properties of affected
      joints and to clinical relevant symptoms. Osteophyte formation is highly
      associated with cartilage damage but osteophytes can develop without explicit
      cartilage damage. Osteophytes are mainly derived from precursor cells in the
      periosteum and growth factors of the TGFbeta superfamily appear to play a crucial
      role in their induction. CONCLUSION: Osteophyte formation is an integral
      component of OA pathogenesis and understanding the biology of osteophyte
      formation can give insights in the disturbed homeostasis in OA joints.

PMID- 17204438
TI  - Injuries in the event horse: training versus competition.
AB  - Two related studies on injuries sustained by event horses during competition and
      during training are reported. During the cross-country phase of competition, the
      most common injuries were lacerations and abrasions to the carpus and stifle.
      Superficial digital flexor tendonitis and exertional rhabdomyolysis were
      significantly more common during Cours Complete Internationale (CCI) competitions
      compared to one-day event (ODE) competitions. The difference in injury types at
      ODEs and CCI competitions probably relates to the increased athletic demands of
      the CCI and the closer veterinary observation at these competitions. The results
      of the training study indicate that 21% of horses intending to compete in a CCI
      did not start due to injury. Forty-three percent of these injuries involved soft
      tissue structures with injuries to the superficial digital flexor tendon and the
      suspensory ligament each accounting for 33%. The most important area for future
      research is investigation of the risk factors for these career-threatening soft
      tissue injuries.

PMID- 17204439
TI  - Sero-prevalence and risk indicators for canine ehrlichiosis in three rural areas
      of Brazil.
AB  - Ehrlichia canis has a worldwide geographic distribution, occurring particularly
      in tropical and subtropical areas. In Brazil, the main vector in urban areas is
      believed to be the brown dog tick Rhipicephalus sanguineus, but little is known
      about the occurrence, transmission and other epidemiological aspects of canine
      ehrlichiosis in rural areas, where Amblyomma ticks are found more frequently than
      R. sanguineus. A sero-prevalence study of canine ehrlichiosis was carried out in
      three distinct rural regions of the State of Minas Gerais, Brazil. Serum samples
      were collected from 226 dogs living on farms in Lavras (n=85), Belo Horizonte
      (n=45), and Nanuque (n=96) and were analyzed by an indirect fluorescent antibody
      test for the detection of anti-Ehrlichia canis antibodies. Age, breed, sex,
      presence of ticks and packed cell volume were also recorded. There were 65.6%
      positive dogs in Nanuque, 37.8% in Belo Horizonte, and 24.7% in Lavras. Animals
      living in Nanuque were 4.6 times more likely to be serologically positive than
      dogs living in the other two regions and antibody titres were considerable higher
      in this area. Male dogs, dogs >5 years of age, those infested with ticks, and
      mongrels all showed higher rates of positivity. The results point to the
      importance of canine ehrlichiosis in rural areas and indicate the need for
      further studies on natural transmission and maintenance of the disease.

PMID- 17204440
TI  - Quantitative sensory testing of patients with long lasting Patellofemoral pain
      syndrome.
AB  - BACKGROUND: Anterior knee pain, diagnosed as Patellofemoral Pain Syndrome (PFPS),
      is one of the most common musculoskeletal problems found in adolescents and young
      adults. There is no consensus in medical literature concerning the aetiology of
      the PFPS. AIMS: To assess by means of Quantitative Sensory Testing (QST) whether
      patients suffering from long-lasting unilateral PFPS demonstrate somatosensory
      dysfunction related to afferent fibres from the local pain area. METHODS: A
      descriptive non-experimental study with two independent samples, consisting of 25
      men and women between 18 and 44 years of age with unilateral PFPS, and a
      comparable group of 23 healthy subjects. Somedic Thermotest apparatus was used to
      assess thresholds of thermal perception, and of heat and cold pain thresholds.
      Von Frey filaments were used to detect tactile sensitivity. Furthermore, quality
      and intensity of knee pain, symptoms and signs from a clinical neurological
      examination were recorded. RESULTS: Decreased sensitivity to tactile stimulation,
      when tested with von Frey filaments, was demonstrated on both the painful and
      pain-free knee in subjects with PFPS, compared to the mean between the knees of
      the control group (p< or =0.001). The mean detection threshold for warmth was
      increased by 1.9 degrees C (p< or =0.01) in the painful knee, and 1.4 degrees C
      (p< or =0.01) in the non-painful knee in the PFPS group, compared to the mean of
      the healthy control group. The mean detection threshold for cold was increased by
      1.6 degrees C (p< or =0.01) in the painful knee of the PFPS group, compared to
      the control group. These findings were supported by clinical sensory tests. No
      significant differences of mean thermal pain thresholds between the PFPS group
      and controls were found, and there were no significant differences in mean
      detection thresholds for warmth, cold or thermal pain thresholds between the
      painful and the non-painful knees in the PFPS group. CONCLUSION: This study
      demonstrated an abnormal sensory function in the painful and non-painful knee in
      some individuals with long lasting unilateral Patellofemoral Pain Syndrome using
      Quantitative Sensory Testing supported by clinical neurological examinations. A
      dysfunction of the peripheral and/or the central nervous system may cause
      neuropathic pain in some subjects with PFPS.

PMID- 17204441
TI  - Quantitative structure spectroscopy relationships of carbon-13 nuclear magnetic
      resonance chemical shifts of steroids.
AB  - Quantitative structure spectroscopy relationships (QSSRs) are systematically
      studied for carbon-13 nuclear magnetic resonance ((13)C NMR) spectroscopic
      simulation of steroid compounds. Both the atomic electronegativity interaction
      vector (AEIV) and the atomic hybridization state index (AHSI) are used for the
      expression of local chemical microenvironment and atomic hybridization state of
      4434 resonance carbon atoms in 203 steroid molecules. A multiple linear
      regression (MLR) model is built after screening some insignificant parameters
      with the stepwise multiple regression (SMR) technique. Correlation coefficients
      of the developed model are R(cum)(2)=0.9341 and Q(LOO)(2)=0.9336 for classical
      estimation of molecular modeling and the cross-validation with leave-one-out
      (LOO) procedures, respectively, primarily indicating that the MLR model has good
      modeling stability and prediction ability. Furthermore, the superior performance
      of the MLR model is tested by the leave-33%-out (L33%O) cross-validation method,
      where the mean correlation coefficients of three test sets are Q(2)=0.9310 and
      Q(ext)(2)=0.9196 for both internal and external sets. In conclusion, AEIV and
      AHSI descriptors can be used for estimating and predicting (13)C NMR chemical
      shifts of steroids.

PMID- 17204442
TI  - Production of p-hydroxycinnamic acid from glucose in Saccharomyces cerevisiae and
      Escherichia coli by expression of heterologous genes from plants and fungi.
AB  - Biological production of p-hydroxycinnamic acid (pHCA) from glucose can be
      achieved via deamination of the aromatic amino acids l-tyrosine or l
      phenylalanine. Deamination of l-phenylalanine produces trans-cinnamic acid (CA)
      which is further hydroxylated in the para position to produce pHCA. However, when
      tyrosine is used as the substrate, trans-pHCA is produced in one step. This
      reaction is accomplished by phenylalanine ammonia-lyase (PAL)/tyrosine ammonia
      lyase (TAL). Various bacteria and eukaryotic microorganisms were screened for
      their ability to produce a PAL/TAL enzyme with high TAL activity. Cell-free
      extracts of the yeast Rhodotorula glutinis possessed the highest level of TAL
      activity (0.0143U/mg protein) and the lowest PAL/TAL ratio (1.68) amongst species
      examined. The gene for this enzyme was cloned and expressed in Escherichia coli
      and the kinetics of the purified PAL/TAL determined. The recombinant PAL/TAL
      possessed characteristics similar to those of the wild-type enzyme. Functional
      expression of R. glutinis PAL/TAL enzyme in Saccharomyces cerevisiae cells
      containing the plant C4H P-450 and P-450 reductase enzymes from Helianthus
      tuberosus allowed conversion of glucose to pHCA. Addition of l-phenylalanine to
      these cultures increased pHCA production confirming its production via the PAL
      route. When R. glutinis PAL/TAL was synthesized in an E. colil-phenylalanine
      producing strain (ATCC 31882) and grown on glucose, pHCA was formed in the
      absence of the Cytochrome P-450 and the P-450 reductase enzymes underlining its
      production via the TAL route without CA intermediacy.

PMID- 17204443
TI  - Extraction of spectral based measures from MEG background oscillations in
      Alzheimer's disease.
AB  - In this study, we explored the ability of several spectral based measures to
      summarize the information of the power spectral density (PSD) function from
      spontaneous magnetoencephalographic (MEG) activity in Alzheimer's disease (AD).
      The MEGs of 20 AD patients and 21 elderly controls were recorded with eyes closed
      at rest during 5 min from 148 channels. Five spectral parameters were estimated
      from PSD: mean frequency (MF), individual alpha frequency (IAF), transition
      frequency (TF), 95% spectral edge frequency (SEF95) and spectral entropy (SE). To
      reduce the dimensionality of the problem, we applied a principal component
      analysis. According to our results, MF was the best discriminating index between
      both groups (85.00% sensitivity, 85.71% specificity) indicating a shift to the
      left of the power spectrum in AD. A significant MEG slowing was also observed
      using both IAF (p < 0.001) and TF (p < 0.01). The lowest classification
      statistics (65% sensitivity, 66.67% specificity) were obtained with SEF95.
      However, these results were also significant (p < 0.05). This fact points out
      that there is a variation in the spectral content at high frequencies of AD
      patients and controls. Finally, a significant decrease of irregularity in the AD
      group was observed with SE, with results close to those obtained with MF (90.00%
      sensitivity, 76.19% specificity). In conclusion, a complete description of PSD
      can help to increase our insight into brain dysfunction in AD and to extract
      spectral patterns specific to the disease.

PMID- 17204444
TI  - Neogenin: A multi-functional receptor regulating diverse developmental processes.
AB  - Neogenin, a close relative of the axon guidance receptor Deleted in Colorectal
      Cancer (DCC), has been shown to be a receptor for members of the Netrin and
      Repulsive Guidance Molecule (RGM) families. While Netrin-1-Neogenin interactions
      result in a chemoattractive axon guidance response, the interaction between
      Neogenin and RGMa induces a chemorepulsive response. Evidence is now accumulating
      that Neogenin is a multi-functional receptor regulating many diverse
      developmental processes, including neural tube and mammary gland formation,
      myogenesis and angiogenesis. Little is known of the function of Neogenin in the
      adult, however, a novel role in the regulation of iron homeostasis is now
      emerging. While the signal transduction pathways activated by Neogenin are poorly
      understood, it is clear that the functional outcome of Neogenin activation, at
      least in the embryo, depends on both the developmental context as well as the
      nature of the ligand.

PMID- 17204445
TI  - Segmentation of blood vessels from red-free and fluorescein retinal images.
AB  - The morphology of the retinal blood vessels can be an important indicator for
      diseases like diabetes, hypertension and retinopathy of prematurity (ROP). Thus,
      the measurement of changes in morphology of arterioles and venules can be of
      diagnostic value. Here we present a method to automatically segment retinal blood
      vessels based upon multiscale feature extraction. This method overcomes the
      problem of variations in contrast inherent in these images by using the first and
      second spatial derivatives of the intensity image that gives information about
      vessel topology. This approach also enables the detection of blood vessels of
      different widths, lengths and orientations. The local maxima over scales of the
      magnitude of the gradient and the maximum principal curvature of the Hessian
      tensor are used in a multiple pass region growing procedure. The growth
      progressively segments the blood vessels using feature information together with
      spatial information. The algorithm is tested on red-free and fluorescein retinal
      images, taken from two local and two public databases. Comparison with first
      public database yields values of 75.05% true positive rate (TPR) and 4.38% false
      positive rate (FPR). Second database values are of 72.46% TPR and 3.45% FPR. Our
      results on both public databases were comparable in performance with other
      authors. However, we conclude that these values are not sensitive enough so as to
      evaluate the performance of vessel geometry detection. Therefore we propose a new
      approach that uses measurements of vessel diameters and branching angles as a
      validation criterion to compare our segmented images with those hand segmented
      from public databases. Comparisons made between both hand segmented images from
      public databases showed a large inter-subject variability on geometric values. A
      last evaluation was made comparing vessel geometric values obtained from our
      segmented images between red-free and fluorescein paired images with the latter
      as the "ground truth". Our results demonstrated that borders found by our method
      are less biased and follow more consistently the border of the vessel and
      therefore they yield more confident geometric values.

PMID- 17204446
TI  - Measurements of DNA damage on silver stained comets using free Internet software.
AB  - Silver stain offers the possibility to stain comets permanently, but up to now it
      was impossible to measure the majority of the comet parameters, because the
      distinction between head and tail was not recognised by software. Here, we report
      a silver staining protocol that allows the measurement of comet parameters using
      the free Internet software CASP. We validated the silver stain protocol by
      comparing the behaviour of the parameter '% DNA in tail' in silver and
      fluorescent stained comets. The range of % DNA in tail for different visual
      categories of damage in silver stained comets was similar to that reported with
      fluorescence staining. The range was for category 0 (no damage), <1%; category 1
      (low damage), 1-25%; category 2 (medium damage), >25-45%; category 3 (high
      damage), >45-70%; category 4 (very high damage), >70%. The mean of % DNA in tail
      in silver stained comets was also similar to that reported with fluorescence
      staining. The mean was for category 0, 0.4+/-0.34%; category 1, 12+/-7%; category
      2, 37+/-4%; category 3, 57+/-5% and category 4, 83+/-6%. Others comet parameters
      such as tail length, tail moment and Olive tail moment can be also measured. The
      silver staining protocol reported here opens new opportunities for those working
      in the assay without fluorescent microscope as the measurement of comet
      parameters using free Internet software and conventional microscope becomes
      possible.

PMID- 17204447
TI  - The investigation of chemical structure of coal macerals via transmitted-light FT
      IR microscopy by X. Sun.
AB  - A recent paper by Sun [X. Sun, Spectrochim. Acta A 62 (1-3) (2005) 557] attempts
      to characterize a variety of liptinite, termed "barkinite", from Chinese Permian
      coals. The component identified does not appear to fundamentally differ from
      previously-described liptinite macerals included in the International Committee
      for Coal and Organic Petrology's system of maceral nomenclature. Further,
      chemical comparisons made with macerals from coals of different rank and age are
      flawed because the author did not account for changes in chemistry with rank or
      for the chemical changes associated with botanical changes through geologic time.
      The author has not satisfactorily proved his hypothesis that the component
      differs morphologically or chemically from known liptinite-group macerals.

PMID- 17204448
TI  - FT-IR vibrational spectrum and DFT:B3LYP/6-31G structure and vibrational analysis
      of guanidinoaceticserinenickel(II) complex: [Ni(GAA)(Ser)].
AB  - Vibrational assignment and structural determination for the
      guanidinoaceticserinenickel(II) complex have been made through DFT:B3LYP/6-31G
      calculations. A full discussion of the framework vibrational modes was done using
      as criteria the geometry study of distorted structures generated for the
      vibrational modes. Incidentally, the normal co-ordinate treatments have been made
      in order to clarify the assignments for the Ni(N)(2)(O)(2) structural fragment.
      The calculated DFT spectra in the high and low energy regions agree well with the
      observed ones.

PMID- 17204449
TI  - FT-IR vibrational spectrum and DFT:B3LYP/6-311G structure and vibrational
      analysis of bis-serinenickel(II) complex: [Ni(Ser)2].
AB  - The bis-serinenickel(II) complex was synthesized, and the Fourier-transforms
      infrared spectra in the regions 4000-370 and 700-30 cm(-1) was measured. The
      second derivative spectra and band deconvolution analysis was also obtained.
      Density functional theory calculations, DFT:B3LYP/6-311G, were performed for the
      determination of geometrical structure and vibrational assignment for the bis
      serinenickel(II) complex. A full discussion of the framework vibrational modes
      was done using as criteria the geometry study of distorted structures generated
      for the vibrational modes. Incidentally, the normal coordinate analysis was
      carried out for the Ni(N)2(O)2 structural fragment. The calculated DFT spectra in
      the high and low energy regions agree well with the observed ones.

PMID- 17204450
TI  - Spectral image analysis for the absorption bands of the beta-methallyl free
      radical in the vapor phase.
AB  - The radicals formed in the flash photolysis of 2-methylbut-1-ene and subsequent
      reactions have been investigated by kinetic spectroscopy and gas liquid
      chromatography. Less than 10% of photo products are formed by a molecular made of
      fission of the excited olefin, and of the radical modes the relative
      probabilities of band fission, beta(CH):beta(CH):alpha(CC) are 13:1.37:1. The
      extinction coefficients of beta-methallyl radical measured experimentally for all
      the absorption bands. The decay of the beta-methallyl radical was second order.
      The rate constant for the beta-methallyl radical recombination experimentally
      measured was 2.6+/-0.3 x 10(10) l mol(-1)s(-1) at 295+/-2K. The spectrum image
      showing the absorption bands was examined by image processing techniques in order
      to improve the visual experience of each band by localizing to a specific region
      of interest. Experimental results illustrate how the exact location of absorption
      bands was clearly extracted from the spectral image and further improvements in
      the visual detection of absorption bands.

PMID- 17204451
TI  - Securing electronic health records without impeding the flow of information.
AB  - OBJECTIVE: We present an integrated set of technologies, known as the Hippocratic
      Database, that enable healthcare enterprises to comply with privacy and security
      laws without impeding the legitimate management, sharing, and analysis of
      personal health information. APPROACH: The Hippocratic Database approach to
      securing electronic health records involves (1) active enforcement of fine
      grained data disclosure policies using query modification techniques, (2)
      efficient auditing of past database access to verify compliance with policies and
      track security breaches, (3) data mining algorithms that preserve privacy by
      randomizing information at the individual level, (4) de-identification of
      personal health data using an optimal method of k-anonymization, and (5)
      information sharing across autonomous data sources using cryptographic protocols.
      CONCLUSIONS: Our research confirms that policies concerning the disclosure of
      electronic health records can be reliably and efficiently enforced and audited at
      the database level. We further demonstrate that advanced data mining and
      anonymization techniques can be employed to analyze aggregate health records
      without revealing individual patient identities. Finally, we show that web
      services and commutative encryption can be used to share sensitive information
      selectively among autonomous entities without compromising security or privacy.

PMID- 17204452
TI  - Pitfalls in diagnosing human poxvirus infections.

PMID- 17204453
TI  - Benefit of detecting tick-borne encephalitis viremia in the first phase of
      illness.
AB  - In Switzerland, reports of tick-borne encephalitis virus (TBEV) infections to the
      Federal Office of Public Health have increased by 100% in 2005 compared to the
      annual mean from 1999 to 2004. This might be partly due to unspecificity in
      serological testing. In order to make diagnostics more specific and to improve
      patient management, we recommend to consider the first phase of the biphasic
      course of TBE, that can be suspected in a trias of tick bite, followed by a
      feverish illness associated with thrombocytopenia and/or leucocytopenia. In this
      phase, detection of viremia by TBEV-specific polymerase chain reaction assay
      (PCR) will enable diagnosis as well as prediction of the second phase of TBEV
      infection, developing in the majority of patients. Circumstances suggesting
      detection of TBE viremia are exemplified by two case reports.

PMID- 17204454
TI  - Effect of serum and CTL on focal growth of human cytomegalovirus.
AB  - BACKGROUND: In immunocompromised patients only cytotoxic T-lymphocytes (CTL) but
      not antiviral antibodies appear to be efficient in control of human
      cytomegalovirus (HCMV) infection. This is contrasted by the well-documented
      neutralising activity of patient sera against standard HCMV strains. OBJECTIVE:
      We tested the hypothesis that a cell-culture model based on a recent clinical
      HCMV isolate would more accurately approximate the clinical situation and provide
      an explanation for the failure of neutralising antibodies in efficient
      restriction of HCMV infection. METHODS: Sera from five bone marrow transplant
      recipients with or without prolonged HCMV replication were analysed by an enzyme
      linked immunoassay for their capacity to neutralise cell-free HCMV preparations.
      The inhibitory effect of these sera on viral cell-to-cell-spread was then
      quantified by focus expansion assays using a recent clinical HCMV-isolate and was
      finally compared to the inhibitory effect of HCMV-specific CTL lines. RESULTS:
      Prolonged HCMV replication occurred in three patients despite high titres of
      neutralising antibodies. In contrast to the strong inhibitory effect on cell-free
      HCMV, their sera could not inhibit the focal growth of a recent cell-associated
      HCMV isolate, whereas CTL clones directed against pUL123 or pUL83 of HCMV
      effectively limited focal expansion of the clinical isolate in fibroblast
      culture. CONCLUSIONS: Focus expansion assays based on a cell-associated clinical
      HCMV isolate provide a model for the in vivo effectiveness of virus-specific CTL
      and neutralising antibodies. Our data support the assumption that due to their
      strict cell-association clinical HCMV strains are withdrawn from neutralising
      antibodies.

PMID- 17204455
TI  - Effects of bile diversion in rats on intestinal sphingomyelinases and ceramidase.
AB  - Alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase (N-CDase) in the
      intestinal microvillar membrane are responsible for dietary sphingomyelin
      digestion. The activities of the enzymes require the presence of bile salt, and
      the enzymes can be released into the gut lumen in active forms by bile salts and
      trypsin. It is unclear to what extent that the intestinal presence of bile salts
      is critical for the intraluminal activity of these enzymes. We compared the
      activities of Alk-SMase, N-CDase, and other types of SMases in control and
      permanently bile diverted rats. In the intestinal tract of control rats, the
      activity of Alk-SMase was profoundly higher than those of acid and neutral
      SMases. Bile diversion reduced Alk-SMase activity by 85% in the small intestinal
      content, and by 68% in the faeces, but did not significantly change the activity
      in the intestinal mucosa. Western blot showed a marked reduction of the enzyme in
      the intestinal lumen but not mucosa. N-CDase activities both in the intestinal
      mucosa and content were reduced by bile diversion. Bile diversion also decreased
      aminopeptidase N activity in the content and increased that in the mucosa, but
      had no effects on that of alkaline phosphatase. In conclusion, the presence of
      bile salts is important for maintaining high intraluminal levels of Alk-SMase and
      N-CDase, two key enzymes for hydrolysis of sphingomyelin in the gut. We speculate
      that the sphingomyelin hydrolysis in cholestatic conditions is impaired not only
      by reduced hydrolytic activity but also by deficient dissociation of the enzymes
      from the membrane.

PMID- 17204457
TI  - Proceedings of the Biomarker Discovery by Mass Spectrometry Symposium, May 18-19,
      2006, Amsterdam, The Netherlands.

PMID- 17204456
TI  - The use of flexible arm muscle synergies to perform an isometric stabilization
      task.
AB  - OBJECTIVE: To evaluate if functional synergies are comprised of flexible
      combinations of a small number of ensembles of upper limb muscles to stabilize a
      particular performance variable during a force production task. METHODS:
      Electromyographic (EMG) signals of wrist, elbow and shoulder muscles were
      recorded. Linear combinations of indices of the integrated EMG of nine muscles
      (muscle modes or M-modes) and their relationship to changes in the moment of
      force produced by the right arm of subjects about the horizontal axis of a handle
      were first determined. Uncontrolled manifold (UCM) analysis was performed to
      determine the extent to which variance of the M-modes acted to produce a
      consistent change in the moment of force. RESULTS: Subjects exhibited three M
      modes, two of which were 'reciprocal' while the third mode was considered a co
      contraction mode. The three M-modes were found to be combined to form synergies
      that produced a consistent change in the moment of force across repetitive
      trials. Variance in the M-mode space that led to consistent changes in the moment
      of force across repetitions was significantly higher than variance that tended to
      produce inconsistent changes in the moment of force. CONCLUSIONS: Flexible
      combinations of activations of ensembles of muscles are organized to stabilize
      the value of or produce consistent changes in the value of important performance
      variables. SIGNIFICANCE: The study of flexible muscle synergies in healthy
      individuals paves the way to understanding abnormal postural and movement
      patterns in individuals with neurological disorders.

PMID- 17204458
TI  - Theoretical calculation of triazolam hydroxylation and endogenous steroid
      inhibition in the active site of CYP3A4.
AB  - CYP3A4 has unusual kinetic characteristics because it has a large active site.
      CYP3A4 produced more 4-hydroxytriazolam than alpha-hydroxytriazolam at
      concentrations of more than 60 muM triazolam, and different steroids had
      different inhibitory effects on the system. To clarify these interesting
      observations, the interactions between substrate and substrate/steroid were
      investigated by theoretical calculations. When two triazolam molecules were
      docked into the active site, the distance between the O-atom and the 4
      hydroxylated site was less than the distance to the alpha-hydroxylated site
      because of interaction between the two triazolam molecules. Estradiol inhibited
      both alpha- and 4-hydroxytriazolam formation by 50%. Dehydroepiandrosterone
      (DHEA) inhibited alpha-hydroxylation more than 4-hydroxytriazolam formation,
      whereas aldosterone had no effect. When one triazolam molecule and one steroid
      molecule were simultaneously docked, estradiol increased the distance between the
      O-atom and the two hydroxylated sites, DHEA only increased the distance between
      the O-atom and alpha-hydroxylated site, and aldosterone did not change the
      distances. The relevant angles of Fe-O-C in the hydroxylated site of triazolam
      also widened, together with increased distance. These findings indicate that
      formation of a substrate and substrate/effector complex in the active site may be
      a factor for determining the enzyme kinetic parameters of CYP3A4.

PMID- 17204459
TI  - Hydroxyapatite/titania sol-gel coatings on titanium-zirconium alloy for
      biomedical applications.
AB  - A simple sol-gel method was developed for hydroxyapatite/titania (HA/TiO(2))
      coatings on non-toxic titanium-zirconium (TiZr) alloy for biomedical
      applications. The HA/TiO(2)-coated TiZr alloy displayed excellent bioactivity
      when soaked in a simulated body fluid (SBF) for an appropriate period.
      Differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction
      and scanning electron microscopy-energy dispersive spectrometry were used to
      characterize the phase transformations and the surface structures and to assess
      the in vitro tests. The HA/TiO(2) layers were spin-coated on the surface of TiZr
      alloy at a speed of 3000rpm for 15s, followed by a heat treatment at 600 degrees
      C for 20min in an argon atmosphere sequentially. The TiO(2) layer exhibited a
      cracked surface and an anatase structure and the HA layer displayed a uniform
      dense structure. Both the TiO(2) and HA layers were 25microm thick, and the total
      thickness of the HA/TiO(2) coatings was 50microm. The TiZr alloy after the above
      HA/TiO(2) coatings displayed excellent bone-like apatite-forming ability when
      soaked in SBF and can be anticipated to be a promising load-bearing implant
      material.

PMID- 17204460
TI  - Effects of parathyroid hormone (1-34) on tibia in an adult rat model for chronic
      alcohol abuse.
AB  - Chronic alcohol abuse is a risk factor for osteoporosis in men. Human recombinant
      parathyroid hormone (1-34) (PTH) therapy increases bone mass in patients with
      osteoporosis. The purpose of the present study was to determine whether PTH is
      effective in increasing bone formation and bone mass in a rat model for
      established osteopenia caused by chronic alcohol abuse. Eight-month-old male
      Sprague Dawley rats were fed the Lieber-DeCarli liquid diet in which 35% of the
      calories were derived from either maltose-dextran or ethanol. Measurements were
      performed 16 weeks later to establish the magnitude of bone changes in the rats
      fed alcohol. High dose PTH (80 microg/kg/day) was administered 5 days/week for 6
      weeks to establish the differential efficacy of hormone therapy on bone formation
      in alcohol consuming and alcohol withdrawn rats. The effects of alcohol and PTH
      on cancellous and cortical bone mass, architecture and turnover were determined
      by densitometry and histomorphometry. Rats fed alcohol had reduced bone mineral
      contents and densities, cancellous and cortical bone areas and cancellous bone
      formation rates compared to pair-fed controls. Following the withdrawal of
      alcohol, indices of bone formation increased compared to baseline values. PTH
      treatment increased bone mineral content and density, bone formation rates,
      cortical bone area, cancellous bone area and trabecular number and thickness, but
      several indices of bone formation were reduced in the presence of continued
      alcohol consumption. These results suggest that alcohol consumption, in addition
      to inducing bone loss, may reduce the efficacy of PTH therapy to reverse
      osteoporosis.

PMID- 17204461
TI  - SNPchip: R classes and methods for SNP array data.
AB  - High-density single nucleotide polymorphism microarrays (SNP chips) provide
      information on a subject's genome, such as copy number and genotype
      (heterozygosity/homozygosity) at a SNP. While fluorescence in situ hybridization
      and karyotyping reveal many abnormalities, SNP chips provide a higher resolution
      map of the human genome that can be used to detect, e.g., aneuploidies,
      microdeletions, microduplications and loss of heterozygosity (LOH). As a variety
      of diseases are linked to such chromosomal abnormalities, SNP chips promise new
      insights for these diseases by aiding in the discovery of such regions, and may
      suggest targets for intervention. The R package SNPchip contains classes and
      methods useful for storing, visualizing and analyzing high density SNP data.
      Originally developed from the SNPscan web-tool, SNPchip utilizes S4 classes and
      extends other open source R tools available at Bioconductor. This has numerous
      advantages, including the ability to build statistical models for SNP-level data
      that operate on instances of the class, and to communicate with other R packages
      that add additional functionality. AVAILABILITY: The package is available from
      the Bioconductor web page at www.bioconductor.org. SUPPLEMENTARY INFORMATION: The
      supplementary material as described in this article (case studies, installation
      guidelines and R code) is available from
      http://biostat.jhsph.edu/~iruczins/publications/sm/

PMID- 17204462
TI  - Oligonucleotide microarray identification of Bacillus anthracis strains using
      support vector machines.
AB  - The capability of a custom microarray to discriminate between closely related DNA
      samples is demonstrated using a set of Bacillus anthracis strains. The microarray
      was developed as a universal fingerprint device consisting of 390 genome
      independent 9mer probes. The genomes of B. anthracis strains are monomorphic and
      therefore, typically difficult to distinguish using conventional molecular
      biology tools or microarray data clustering techniques. Using support vector
      machines (SVMs) as a supervised learning technique, we show that a low-density
      fingerprint microarray contains enough information to discriminate between B.
      anthracis strains with 90% sensitivity using a reference library constructed from
      six replicate arrays and three replicates for new isolates.

PMID- 17204463
TI  - MinSet: a general approach to derive maximally representative database subsets by
      using fragment dictionaries and its application to the SCOP database.
AB  - MOTIVATION: The size of current protein databases is a challenge for many
      Bioinformatics applications, both in terms of processing speed and information
      redundancy. It may be therefore desirable to efficiently reduce the database of
      interest to a maximally representative subset. RESULTS: The MinSet method employs
      a combination of a Suffix Tree and a Genetic Algorithm for the generation,
      selection and assessment of database subsets. The approach is generally
      applicable to any type of string-encoded data, allowing for a drastic reduction
      of the database size whilst retaining most of the information contained in the
      original set. We demonstrate the performance of the method on a database of
      protein domain structures encoded as strings. We used the SCOP40 domain database
      by translating protein structures into character strings by means of a structural
      alphabet and by extracting optimized subsets according to an entropy score that
      is based on a constant-length fragment dictionary. Therefore, optimized subsets
      are maximally representative for the distribution and range of local structures.
      Subsets containing only 10% of the SCOP structure classes show a coverage of >90%
      for fragments of length 1-4. AVAILABILITY:
      http://mathbio.nimr.mrc.ac.uk/~jkleinj/MinSet. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 17204464
TI  - SChiSM2: creating interactive web page annotations of molecular structure models
      using Jmol.
AB  - SChiSM2 is a web server-based program for creating web pages that include
      interactive molecular graphics using the freely-available applet, Jmol, for
      illustration. The program works with Internet Explorer and Firefox on Windows,
      Safari and Firefox on Mac OSX and Firefox on Linux. AVAILABILITY: The program can
      be accessed at the following address: http://ci.vbi.vt.edu/cammer/schism2.html.

PMID- 17204465
TI  - In search of the small ones: improved prediction of short exons in vertebrates,
      plants, fungi and protists.
AB  - MOTIVATION: Prediction of the coding potential for stretches of DNA is crucial in
      gene calling and genome annotation, where it is used to identify potential exons
      and to position their boundaries in conjunction with functional sites, such as
      splice sites and translation initiation sites. The ability to discriminate
      between coding and non-coding sequences relates to the structure of coding
      sequences, which are organized in codons, and by their biased usage. For
      statistical reasons, the longer the sequences, the easier it is to detect this
      codon bias. However, in many eukaryotic genomes, where genes harbour many
      introns, both introns and exons might be small and hard to distinguish based on
      coding potential. RESULTS: Here, we present novel approaches that specifically
      aim at a better detection of coding potential in short sequences. The methods use
      complementary sequence features, combined with identification of which features
      are relevant in discriminating between coding and non-coding sequences. These
      newly developed methods are evaluated on different species, representative of
      four major eukaryotic kingdoms, and extensively compared to state-of-the-art
      Markov models, which are often used for predicting coding potential. The main
      conclusions drawn from our analyses are that (1) combining complementary sequence
      features clearly outperforms current Markov models for coding potential
      prediction in short sequence fragments, (2) coding potential prediction benefits
      from length-specific models, and these models are not necessarily the same for
      different sequence lengths and (3) comparing the results across several species
      indicates that, although our combined method consistently performs extremely
      well, there are important differences across genomes. SUPPLEMENTARY DATA:
      http://bioinformatics.psb.ugent.be/.

PMID- 17204466
TI  - Parasporin-1, a novel cytotoxic protein from Bacillus thuringiensis, induces Ca2+
      influx and a sustained elevation of the cytoplasmic Ca2+ concentration in toxin
      sensitive cells.
AB  - Parasporin-1 is a novel non-insecticidal inclusion protein from Bacillus
      thuringiensis that is cytotoxic to specific mammalian cells. In this study, we
      investigated the effects of parasporin-1 on toxin-sensitive cell lines to
      elucidate the cytotoxic mechanism of parasporin-1. Parasporin-1 is not a membrane
      pore-forming toxin as evidenced by measurements of lactate dehydrogenase release,
      propidium iodide penetration, and membrane potential in parasporin-1-treated
      cells. Parasporin-1 decreased the level of cellular protein and DNA synthesis in
      parasporin-1-sensitive HeLa cells. The earliest change observed in cells treated
      with this toxin was a rapid elevation of the intracellular free-Ca(2+)
      concentration; increases in the intracellular Ca(2+) levels were observed 1-3 min
      following parasporin-1 treatment. Using four different cell lines, we found that
      the degree of cellular sensitivity to parasporin-1 was positively correlated with
      the size of the increase in the intracellular Ca(2+) concentration. The toxin
      induced elevation of the intracellular Ca(2+) concentration was markedly
      decreased in low-Ca(2+) buffer and was not observed in Ca(2+)-free buffer.
      Accordingly, the cytotoxicity of parasporin-1 decreased in the low-Ca(2+) buffer
      and was restored by the addition of Ca(2+) to the extracellular medium. Suramin,
      which inhibits trimeric G-protein signaling, suppressed both the Ca(2+) influx
      and the cytotoxicity of parasporin-1. In parasporin-1-treated HeLa cells,
      degradation of pro-caspase-3 and poly(ADP-ribose) polymerase was observed.
      Furthermore, synthetic caspase inhibitors blocked the cytotoxic activity of
      parasporin-1. These results indicate that parasporin-1 activates apoptotic
      signaling in these cells as a result of the increased Ca(2+) level and that the
      Ca(2+) influx is the first step in the pathway that underlies parasporin-1
      toxicity.

PMID- 17204467
TI  - Regulation of Nanog expression by phosphoinositide 3-kinase-dependent signaling
      in murine embryonic stem cells.
AB  - Embryonic stem (ES) cell pluripotency is regulated by a combination of extrinsic
      and intrinsic factors. Previously we have demonstrated that phosphoinositide 3
      kinase (PI3K)-dependent signaling is required for efficient self-renewal of
      murine ES cells. In the study presented here, we have investigated the downstream
      molecular mechanisms that contribute to the ability of PI3Ks to regulate
      pluripotency. We show that inhibition of PI3K activity with either
      pharmacological or genetic tools results in decreased expression of RNA for the
      homeodomain transcription factor Nanog and decreased Nanog protein levels.
      Inhibition of glycogen synthase kinase 3 (GSK-3) activity by PI3Ks plays a key
      role in regulation of Nanog expression, because blockade of GSK-3 activity
      effectively reversed the effects of PI3K inhibition on Nanog RNA, and protein
      expression and self-renewal under these circumstances were restored. Furthermore,
      GSK-3 mutants mimicked the effects of PI3K or GSK-3 inhibition on Nanog
      expression. Importantly, expression of an inducible form of Nanog prevented the
      loss of self-renewal observed upon inhibition of PI3Ks, supporting a functional
      relationship between PI3Ks and Nanog expression. In addition, expression of a
      number of putative Nanog target genes was sensitive to PI3K inhibition. Thus, the
      new evidence provided in this study shows that PI3K-dependent regulation of ES
      cell self-renewal is mediated, at least in part, by the ability of PI3K signaling
      to maintain Nanog expression. Regulation of GSK-3 activity by PI3Ks appears to
      play a key role in this process.

PMID- 17204468
TI  - CXCR1 and CXCR2 activation and regulation. Role of aspartate 199 of the second
      extracellular loop of CXCR2 in CXCL8-mediated rapid receptor internalization.
AB  - CXCL8 (interleukin-8) interacts with two receptors, CXCR1 and CXCR2, to activate
      leukocytes. Upon activation, CXCR2 internalizes very rapidly relative to CXCR1 (
      approximately 90% versus approximately 10% after 5 min). The C termini of the
      receptors have been shown to be necessary for internalization but are not
      sufficient to explain the distinct kinetics of down-regulation. To determine the
      structural determinant(s) that modulate receptor internalization, various
      chimeric and point mutant receptors were generated by progressively exchanging
      specific domains or amino acids between CXCR1 and CXCR2. The receptors were
      stably expressed in rat basophilic leukemia 2H3 cells and characterized for
      receptor binding, intracellular Ca(2+) mobilization, phosphoinositide hydrolysis,
      phosphorylation, internalization, and MAPK activation. The data herein indicate
      that the second extracellular loop (2ECL) of the receptors is critical for the
      distinct rate of internalization. Replacing the 2ECL of CXCR2 with that of CXCR1
      (B(2ECL)A) or Asp(199) with its CXCR1 valine counterpart (B(D199V)A) delayed
      CXCR2 internalization similarly to CXCR1. Replacing Asp(199) with Asn (B(D199N))
      restored CXCR2 rapid internalization. Structure modeling of the 2ECL of the
      receptors also suggested that Asp(199) plays a critical role in stabilizing and
      modulating CXCR2 rapid internalization relative to CXCR1. B(D199N) internalized
      rapidly but migrated as a single phosphorylated form like CXCR1 ( approximately
      75 kDa), whereas B(2ECL)A and B(D199V)A showed slow and fast migrating forms like
      CXCR2 ( approximately 45 and approximately 65 kDa, respectively) but internalized
      like CXCR1. These data further undermine the role of receptor oligomerization in
      CXCL8 receptor internalization. Like CXCR1, B(D199V)A also induced sustained ERK
      activation and cross-desensitized Ca(2+) mobilization to CCR5 relative to
      B(D199N) and CXCR2. Altogether, the data suggest that the 2ECL of the CXCL8
      receptors is important in modulating their distinct rate of down-regulation and
      thereby signal length and post-internalization activities.

PMID- 17204469
TI  - MT1-MMP controls tumor-induced angiogenesis through the release of semaphorin 4D.
AB  - The semaphorins are a family of proteins originally identified as regulators of
      axon growth that recently have been implicated in blood vessel development. The
      plexins are high affinity receptors for the semaphorins and are responsible for
      initiation of signaling upon ligation. Emerging evidence indicates that many
      human cancers overexpress Semaphorin 4D, which promotes neovascularization upon
      stimulating its receptor, Plexin-B1, on endothelial cells. However, to exert its
      pro-angiogenic functions, Semaphorin 4D must be processed and released from its
      membrane bound form to act in a paracrine manner on endothelial cells. Here we
      show that Semaphorin 4D is a novel target for the membrane-tethered collagenase
      membrane type 1-matrix metalloproteinase. We demonstrate that this
      metalloproteinase, which is not expressed in normal or immortal but non
      tumorigenic epithelial cell lines, was present in several head and neck squamous
      cell carcinoma cell lines and was required for processing and release of
      Semaphorin 4D into its soluble form from these cells, thereby inducing
      endothelial cell chemotaxis in vitro and blood vessel growth in vivo. These
      results suggest that the proteolytic cleavage of Semaphorin 4D may provide a
      novel molecular mechanism by which membrane type 1-matrix metalloproteinase
      controls tumor-induced angiogenesis.

PMID- 17204470
TI  - The role of histone acetylation in regulating early gene expression patterns
      during early embryonic stem cell differentiation.
AB  - We have examined the role of histone acetylation in the very earliest steps of
      differentiation of mouse embryonic stem cells in response to withdrawal of
      leukemia inhibitory factor (LIF) as a differentiation signal. The cells undergo
      dramatic changes in morphology and an ordered program of gene expression changes
      representing differentiation to all three germ layers over the first 3-5 days of
      LIF withdrawal. We observed a global increase in acetylation on histone H4 and to
      a lesser extent on histone H3 over this time period. Treatment of the cells with
      trichostatin A (TSA), a histone deacetylase inhibitor, induced changes in
      morphology, gene expression, and histone acetylation that mimicked
      differentiation induced by withdrawal of LIF. We examined localized histone
      acetylation in the regulatory regions of genes that were transcriptionally either
      active in undifferentiated cells, induced during differentiation, or inactive
      under all treatments. There was striking concordance in the histone acetylation
      patterns of specific genes induced by both TSA and LIF withdrawal. Increased
      histone acetylation in local regions correlated best with induction of gene
      expression. Finally, TSA treatment did not support the maintenance or progression
      of differentiation. Upon removal of TSA, the cells reverted to the
      undifferentiated phenotype. We concluded that increased histone acetylation at
      specific genes played a role in their expression, but additional events are
      required for maintenance of differentiated gene expression and loss of the
      pluripotent state.

PMID- 17204471
TI  - Receptor subtype-specific docking of Asp6.59 with C-terminal arginine residues in
      Y receptor ligands.
AB  - Y receptors (YRs) are G protein-coupled receptors whose Y(1)R, Y(2)R, and Y(5)R
      subtypes preferentially bind neuropeptide Y (NPY) and peptide YY, whereas
      mammalian Y(4)Rs show a higher affinity for pancreatic polypeptide (PP).
      Comparison of YR orthologs and paralogs revealed Asp(6.59) to be fully conserved
      throughout all of the YRs reported so far. By replacing this conserved aspartic
      acid residue with alanine, asparagine, glutamate, and arginine, we now show that
      this residue plays a crucial role in binding and signal transduction of NPY/PP at
      all YRs. Sensitivity to distinct replacements is, however, receptor subtype
      specific. Next, we performed a complementary mutagenesis approach to identify the
      contact site of the ligand. Surprisingly, this conserved residue interacts with
      two different ligand arginine residues by ionic interactions; although in Y(2)R
      and Y(5)R, Arg(33) is the binding partner of Asp(6.59), in Y(1)R and Y(4)R,
      Arg(35) of human PP and NPY interacts with Asp(6.59). Furthermore, Arg(25) of PP
      and NPY is involved in ligand binding only at Y(2)R and Y(5)R. This suggests
      significant differences in the docking of YR ligands between Y(1/4)R and Y(2/5)R
      and provides new insights into the molecular binding mode of peptide agonists at
      GPCRs. Furthermore, the proposed model of a subtype-specific binding mode is in
      agreement with the evolution of YRs.

PMID- 17204472
TI  - Electron paramagnetic resonance spectroscopy of site-directed spin labels reveals
      the structural heterogeneity in the N-terminal domain of apoA-I in solution.
AB  - Apolipoprotein A-I (apoA-I) is the major protein constituent of high density
      lipoprotein (HDL) and plays a central role in phospholipid and cholesterol
      metabolism. This 243-residue long protein is remarkably flexible and assumes
      numerous lipid-dependent conformations. Consequently, definitive structural
      determination of lipid-free apoA-I in solution has been difficult. Using electron
      paramagnetic spectroscopy of site-directed spin labels in the N-terminal domain
      of apoA-I (residues 1-98) we have mapped a mixture of secondary structural
      elements, the composition of which is consistent with findings from other in
      solution methods. Based on side chain mobility and their accessibility to polar
      and non-polar spin relaxers, the precise location of secondary elements for amino
      acids 14-98 was determined for both lipid-free and lipid-bound apoA-I. Based on
      intermolecular dipolar coupling at positions 26, 44, and 64, these secondary
      structural elements were arranged into a tertiary fold to generate a structural
      model for lipid-free apoA-I in solution.

PMID- 17204473
TI  - Viral infections activate types I and III interferon genes through a common
      mechanism.
AB  - Viral infections trigger innate immune responses, including the production of
      type I interferons (IFN-alpha and -beta) and other proinflammatory cytokines.
      Novel antiviral cytokines IFN-lambda1, IFN-lambda2, and IFN-lambda3 are
      classified as type III IFNs and have evolved independently of type I IFNs. Type
      III IFN genes are regulated at the level of transcription and induced by viral
      infection. Although the regulatory mechanism of type I IFNs is well elucidated,
      the expression mechanism of IFN-lambdas is not well understood. Here, we analyzed
      the mechanism by which IFN-lambda gene expression is induced by viral infections.
      Loss- and gain-of-function experiments revealed the involvement of RIG-I
      (retinoic acid-inducible gene I), IPS-1, TBK1, and interferon regulatory factor
      3, key regulators of the virus-induced activation of type I IFN genes. Consistent
      with this, a search for the cis-regulatory element of the human ifnlambda1
      revealed a cluster of interferon regulatory factor-binding sites and a NF-kappaB
      binding site. Functional analysis demonstrated that all of these sites are
      essential for gene activation by the virus. These results strongly suggest that
      types I and III IFN genes are regulated by a common mechanism.

PMID- 17204475
TI  - Structural analysis of Xanthomonas XopD provides insights into substrate
      specificity of ubiquitin-like protein proteases.
AB  - XopD (Xanthomonas outer protein D), a type III secreted effector from Xanthomonas
      campestris pv. vesicatoria, is a desumoylating enzyme with strict specificity for
      its plant small ubiquitin-like modifier (SUMO) substrates. Based on SUMO sequence
      alignments and peptidase assays with various plant, yeast, and mammalian SUMOs,
      we identified residues in SUMO that contribute to XopD/SUMO recognition. Further
      predictions regarding the enzyme/substrate specificity were made by solving the
      XopD crystal structure. By incorporating structural information with sequence
      alignments and enzyme assays, we were able to elucidate determinants of the rigid
      SUMO specificity exhibited by the Xanthomonas virulence factor XopD.

PMID- 17204474
TI  - Radical sites in Mycobacterium tuberculosis KatG identified using electron
      paramagnetic resonance spectroscopy, the three-dimensional crystal structure, and
      electron transfer couplings.
AB  - Catalase-peroxidase (KatG) from Mycobacterium tuberculosis, a Class I peroxidase,
      exhibits high catalase activity and peroxidase activity with various substrates
      and is responsible for activation of the commonly used antitubercular drug,
      isoniazid (INH). KatG readily forms amino acid-based radicals during turnover
      with alkyl peroxides, and this work focuses on extending the identification and
      characterization of radicals forming on the millisecond to second time scale.
      Rapid freeze-quench electron paramagnetic resonance spectroscopy (RFQ-EPR)
      reveals a change in the structure of the initially formed radical in the presence
      of INH. Heme pocket binding of the drug and knowledge that KatG[Y229F] lacks this
      signal provides evidence for radical formation on residue Tyr(229). High field
      RFQ-EPR spectroscopy confirmed a tryptophanyl radical signal, and new analyses of
      X-band RFQ-EPR spectra also established its presence. High field EPR spectroscopy
      also confirmed that the majority radical species is a tyrosyl radical. Site
      directed mutagenesis, along with simulations of EPR spectra based on x-ray
      structural data for particular tyrosine and tryptophan residues, enabled
      assignments based on predicted hyperfine coupling parameters. KatG mutants W107F,
      Y229F, and the double mutant W107F/Y229F showed alteration in type and yield of
      radical species. Results are consistent with formation of a tyrosyl radical
      reasonably assigned to residue Tyr(229) within the first few milliseconds of
      turnover. This is followed by a mixture of tyrosyl and tryptophanyl radical
      species and finally to only a tyrosyl radical on residue Tyr(353), which lies
      more distant from the heme. The radical processing of enzyme lacking the Trp(107)
      Tyr(229)-Met(255) adduct (found as a unique structural feature of catalase
      peroxidases) is suggested to be a reasonable assignment of the phenomena.

PMID- 17204476
TI  - JunB and JunD regulate human heme oxygenase-1 gene expression in renal epithelial
      cells.
AB  - Heme oxygenase-1 is a highly inducible gene, the product of which catalyzes
      breakdown of the prooxidant heme. The purpose of this study was to investigate
      the regulation of the human heme oxygenase-1 gene in renal epithelial cells.
      DNase I hyper-sensitivity studies identified three distal sites (HS-2, -3, and 
      4) corresponding to approximately -4.0, -7.2, and -9.2 kb, respectively, of the
      heme oxygenase-1 promoter in addition to one proximal region, HS-1, which we have
      shown previously to be an E box. In vivo dimethyl sulfate footprinting of the HS
      2 region revealed six individual protected guanines. Two mutations within HS-2
      combined with a third mutation of the proximal E box abolished hemin- and cadmium
      driven heme oxygenase-1 promoter activation, suggesting that these three sites
      synergized for maximal heme oxygenase-1 induction. Jun proteins bound to the
      antioxidant response element in the HS-2 region in vitro and associated with the
      heme oxygenase-1 promoter in vivo. JunB and JunD contribute opposing effects;
      JunB activated whereas JunD repressed heme oxygenase-1 expression in human renal
      epithelial cells, results that were corroborated in junB(-)(/)(-) and junD(-)(/)(
      ) cells. We propose that heme oxygenase-1 induction is controlled by a dynamic
      interplay of regulatory proteins, and we provide new insights into the molecular
      control of the human heme oxygenase-1 gene.

PMID- 17204477
TI  - The collagens of hydra provide insight into the evolution of metazoan
      extracellular matrices.
AB  - A collagen-based extracellular matrix is one defining feature of all Metazoa. The
      thick sheet-like extracellular matrix (mesoglia) of the diploblast, hydra, has
      characteristics of both a basement membrane and an interstitial matrix. Several
      genes associated with mesoglea have been cloned including a basement membrane and
      fibrillar collagen and an A and B chain of laminin. Here we report the
      characterization of a further three fibrillar collagen genes (Hcol2, Hcol3, and
      Hcol5) and the partial sequence of a collagen gene with a unique structural
      organization consisting of multiple von Willebrand factor A domains interspersed
      with interrupted collagenous triple helices (Hcol6) from Hydra vulgaris. Hcol2
      and -5 have major collagenous domains of classical length ( approximately 1020
      amino acid residues), whereas the equivalent domain in Hcol3 is shorter (969
      residues). The N-propeptide of Hcol2 contains a whey acid protein four-cysteine
      repeat (WAP) domain, and the equivalent domain of Hcol3 contains two WAP and two
      von Willebrand factor A domains. Phylogenetic analyses reveal that the hydra
      fibrillar collagen genes form a distinct clade that appears related to the
      protostome/deuterostome A clade of fibrillar collagens. Data base searches reveal
      Hcol2, -5, and -6 are highly conserved in Hydra magnipapillata, which also
      provided preliminary evidence for the expression of a B-clade fibrillar collagen.
      All four of the H. vulgaris collagens are expressed specifically by the ectoderm.
      The expression pattern for Hcol2 is similar to that previously reported for Hcol1
      (Deutzmann, R., Fowler, S., Zhang, X., Boone, K., Dexter, S., Boot-Handford, R.
      P., Rachel, R., and Sarras, M. P., Jr. (2000) Development 127, 4669-4680) but
      distinct from the pattern shared by Hcol3 and Hcol5. The characterization of
      multiple collagen genes in relatively simple diploblastic organisms provides new
      insights into the molecular evolution of collagens and the origins of the
      collagen-based extracellular matrix found throughout the multicellular animal
      kingdom.

PMID- 17204478
TI  - Molecular interactions between MASP-2, C4, and C2 and their activation fragments
      leading to complement activation via the lectin pathway.
AB  - Activation of component C3 is central to the pathways of complement and leads
      directly to neutralization of pathogens and stimulation of adaptive immune
      responses. The convertases that catalyze this reaction assemble from fragments of
      complement components via multistep reactions. In the lectin pathway, mannose
      binding lectin (MBL) and ficolins bind to pathogens and activate MBL-associated
      serine protease-2 (MASP-2). MASP-2 cleaves C4 releasing C4a and generating C4b,
      which attaches covalently to the pathogen surface upon exposure of its reactive
      thioester. C2 binds to C4b and is also cleaved by MASP-2 to form the C3
      convertase (C4b2a). To understand how this complex process is coordinated, we
      have analyzed the interactions between MASP-2, C4, C2, and their activation
      fragments and have compared MASP-2-catalyzed cleavage of C4b2 and C2. The data
      show that C2 binds tightly to C4b but not to C4, implying that C4 and C2 do not
      circulate as preformed complexes but that C2 is recruited only after prior
      activation of C4. Following cleavage of C4, C4b still binds to MASP-2 (KD
      approximately 0.6 microM) and dissociates relatively slowly (koff approximately
      0.06 s-1) compared with the half-life of the thioester (<or=0.7 s) (Sepp, A.,
      Dodds, A. W., Anderson, M. J., Campbell, R. D., Willis, A. C., and Law, S. K.
      (1993) Protein Sci. 2, 706-716). We propose that the C4b.MASP-2 interaction
      favors attachment of C4b near to the activating MBL.MASP complex on the bacterial
      surface so that, following recruitment of C2, the proximity of enzyme and
      substrate (C4b2) combined with more favorable reaction kinetics drive the
      formation of the C3 convertase, promoting complement activation.

PMID- 17204479
TI  - Identification of a novel chondroitin-sulfated collagen in the membrane
      separating theca and granulosa cells in chicken ovarian follicles: the granulosa
      theca cell interface is not a bona fide basement membrane.
AB  - The membranous structure separating the granulosa from theca cells in the
      developing ovarian follicles of birds is generally perceived as a genuine
      basement membrane (BM). Previously, we suggested that this membrane is unusual in
      that it lacks several typical BM components, e.g. collagen IV, laminin B,
      perlecan, and fibronectin (Hummel, S., Osanger, A., Bajari, T. M., Balasubramani,
      M., Halfter, W., Nimpf, J., and Schneider, W. J. (2004) J. Biol. Chem. 279, 23486
      23494). We have now identified a novel chondroitin sulfate-modified collagen,
      tentatively termed ggBM1 (Gallus gallus basement membrane protein1) as a major
      component of the border between the vascularized theca and the epitheloid
      granulosa cells. In biosynthetic experiments using [3H]proline and [35S]sulfate,
      ggBM1 was shown to be synthesized by and secreted from the granulosa cells that
      support the developing oocyte. The acidic heterogeneous 135-kDa proteoglycan was
      converted to a protein with an apparent Mr of 95,000 by treatment with
      chondroitinase ABC and was completely degraded by collagenase. Sequencing of
      tryptic fragments revealed peptides typical of collagens. The follicular BM
      accumulated apolipoprotein B and apo-VLDLII, the major resident proteins of the
      yolk precursor very low density lipoprotein. Interestingly, and likely indicating
      an analogous situation to the follicle, ggBM1 is also a component of Bruch's
      membrane of the eye, which separates the vascularized choroid from retinal
      pigmented epithelial cells. Based on our data we propose that in addition to
      thecal perlecan, ggBM1 is involved in the transfer of yolk precursors from the
      thecal capillary bed to oocyte surface lipoprotein receptors mediating their
      uptake into oocytes.

PMID- 17204480
TI  - Insights into the multiple roles of pausing in HIV-1 reverse transcriptase
      promoted strand transfers.
AB  - We previously analyzed the role of pausing induced by hairpin structures within
      RNA templates in facilitating strand transfer by HIV-1 RT (reverse
      transcriptase). We proposed a multistep transfer mechanism in which pause-induced
      RNase H cuts within the initial RNA template (donor) expose regions of cDNA. A
      second homologous RNA template (acceptor) can interact with the cDNA at such
      sites, initiating transfer. The acceptor-cDNA hybrid is thought to then propagate
      by branch-migration, eventually catching up with the primer terminus and
      completing the transfer. The prominent pause site in the template system
      facilitated acceptor invasion; however, very few of the transfers terminated at
      this pause. To examine the effects of homology on pause-promoted transfer, we
      increased template homology before the pause site, from 19 nucleotides (nt) in
      the initial template system to 52 nt in the new system. Significantly, the
      increased homology enhanced transfers 3-fold, with 32% of the transfers now
      terminating at the pause site. Additionally, the acceptor cleavage profile
      indicated the creation of a new invasion site in the added region of homology. NC
      (nucleocapsid) increased the strand transfer throughout the whole template.
      However, the prominent hot spot for internal transfer remained, which was still
      at the pause site. We interpret the new results to mean that pause sites can also
      serve to stall DNA synthesis, allowing acceptor invasions initiated earlier in
      the template to catch up with the primer terminus.

PMID- 17204481
TI  - Functional analysis of norcoclaurine synthase in Coptis japonica.
AB  - (S)-Norcoclaurine is the entry compound in benzylisoquinoline alkaloid
      biosynthesis and is produced by the condensation of dopamine and 4
      hydroxyphenylacetaldehyde (4-HPAA) by norcoclaurine synthase (NCS) (EC 4.2.1.78).
      Although cDNA of the pathogenesis-related (PR) 10 family, the translation product
      of which catalyzes NCS reaction, has been isolated from Thalictrum flavum, its
      detailed enzymological properties have not yet been characterized. We report here
      that a distinct cDNA isolated from Coptis japonica (CjNCS1) also catalyzed NCS
      reaction as well as a PR10 homologue of C. japonica (CjPR10A). Both recombinant
      proteins stereo-specifically produced (S)-norcoclaurine by the condensation of
      dopamine and 4-HPAA. Because a CjNCS1 cDNA that encoded 352 amino acids showed
      sequence similarity to 2-oxoglutarate-dependent dioxygenases of plant origin, we
      characterized the properties of the native enzyme. Sequence analysis indicated
      that CjNCS1 only contained a Fe(2+)-binding site and lacked the 2-oxoglutarate
      binding domain. In fact, NCS reaction of native NCS isolated from cultured C.
      japonica cells did not depend on 2-oxoglutarate or oxygen, but did require
      ferrous ion. On the other hand, CjPR10A showed no specific motif. The addition of
      o-phenanthroline inhibited NCS reaction of both native NCS and recombinant
      CjNCS1, but not that of CjPR10A. In addition, native NCS and recombinant CjNCS1
      accepted phenylacetaldehyde and 3,4-dihydroxyphenylacetaldehyde, as well as 4
      HPAA, for condensation with dopamine, whereas recombinant CjPR10A could use 4
      hydroxyphenylpyruvate and pyruvate in addition to the above aldehydes. These
      results suggested that CjNCS1 is the major NCS in C. japonica, whereas native NCS
      extracted from cultured C. japonica cells was more active and formed a larger
      complex compared with recombinant CjNCS1.

PMID- 17204482
TI  - Convergence of p53 and transforming growth factor beta (TGFbeta) signaling on
      activating expression of the tumor suppressor gene maspin in mammary epithelial
      cells.
AB  - Using two-dimensional difference gel electrophoresis, we identified the tumor
      suppressor gene maspin as a transforming growth factor beta (TGFbeta) target gene
      in human mammary epithelial cells. TGFbeta up-regulatesMaspin expression both at
      the RNA and protein levels. This up-regulation required Smad2/3 function and
      intact p53-binding elements in the Maspin promoter. DNA affinity immunoblot and
      chromatin immunoprecipitation revealed the presence of both Smads and p53 at the
      Maspin promoter in TGFbeta-treated cells, suggesting that both transcription
      factors cooperate to induce Maspin transcription. TGFbeta did not activate Maspin
      luciferase reporter in p53-mutant MDA-MB-231 breast cancer cells, which exhibit
      methylation of the endogenous Maspin promoter. Expression of ectopic p53,
      however, restored ligand-induced association of Smad2/3 with a transfected Maspin
      promoter. Stable transfection of Maspin inhibited basal and TGFbeta-stimulated
      MDA-MB-231 cell motility. Finally, knockdown of endogenous Maspin in p53 wild
      type MCF10A/HER2 cells enhanced basal and TGFbeta-stimulated motility. Taken
      together, these data support cooperation between the p53 and TGFbeta tumor
      suppressor pathways in the induction of Maspin expression, thus leading to
      inhibition of cell migration.

PMID- 17204483
TI  - Deinococcus radiodurans RNA ligase exemplifies a novel ligase clade with a
      distinctive N-terminal module that is important for 5'-PO4 nick sealing and
      ligase adenylylation but dispensable for phosphodiester formation at an
      adenylylated nick.
AB  - Deinococcus radiodurans RNA ligase (DraRnl) is a template-directed ligase that
      seals nicked duplexes in which the 3'-OH strand is RNA. DraRnl is a 342 amino
      acid polypeptide composed of a C-terminal adenylyltransferase domain fused to a
      distinctive 126 amino acid N-terminal module (a putative OB-fold). An alanine
      scan of the C domain identified 9 amino acids essential for nick ligation, which
      are located within nucleotidyltransferase motifs I, Ia, III, IIIa, IV and V.
      Seven mutants were dysfunctional by virtue of defects in ligase adenylylation:
      T163A, H167A, G168A, K186A, E230A, F281A and E305A. Four of these were also
      defective in phosphodiester formation at a preadenylylated nick: G168A, E230A,
      F281A and E305A. Two nick sealing-defective mutants were active in ligase
      adenylylation and sealing a preadenylylated nick, thereby implicating Ser185 and
      Lys326 in transfer of AMP from the enzyme to the nick 5'-PO(4). Whereas deletion
      of the N-terminal domain suppressed overall nick ligation and ligase
      adenylylation, it did not compromise sealing at a preadenylylated nick.
      Mutational analysis of 15 residues of the N domain identified Lys26, Gln31 and
      Arg79 as key constituents. Structure-activity relationships at the essential
      residues were determined via conservative substitutions. We propose that DraRnl
      typifies a new clade of polynucleotide ligases. DraRnl homologs are detected in
      several eukaryal proteomes.

PMID- 17204485
TI  - Human allergy and geohelminth infections: a review of the literature and a
      proposed conceptual model to guide the investigation of possible causal
      associations.
AB  - Geohelminth infections and allergic disease are major public health problems and
      there is evidence in developing countries that they are associated. Although
      there is an extensive literature of the relationship between geohelminth
      infections and allergy, there is little consensus on whether the association is
      causal and if so, whether geohelminth infections may increase or decrease the
      risk of allergy. An explanation for the conflicting findings of epidemiological
      studies is that geohelminths decrease the risk of allergy in areas of high
      infection prevalence and increase the risk of allergy in areas of low prevalence.
      Chronic geohelminth infections are inversely associated with allergy and
      anthelmintic treatment may increase the prevalence of allergy. In this paper, we
      review studies that have investigated the relationship between geohelminths and
      allergy; discuss the relevance of prevalence and timing of geohelminth infections
      and propose a conceptual model to define relevant scientific questions in future
      human and animal studies.

PMID- 17204486
TI  - Access anxiety: HIPAA and historical research.
AB  - The Health Insurance Portability and Accountability Act of 1996 (HIPAA)
      establishes new standards for the protection of private health information in the
      United States. The Privacy Rule, one of the specific regulatory provisions of the
      act, went into effect 14 April 2003 for covered health care providers,
      institutions, and businesses. The Privacy Rule directly affected medical
      archivists and their collections. It has significant implications for historians
      of health care, as well. The Privacy Rule is the first major regulation that
      protects the privacy of the deceased in perpetuity. It establishes requirements
      that researchers must satisfy in order to gain access to "individually
      identifiable health information" held by HIPAA-protected institutions. While
      these requirements will burden historians in some cases, the Privacy Rule could
      open up opportunities for well-prepared historians to work with a more extensive
      range of twentieth-century documents.

PMID- 17204484
TI  - Positional clustering improves computational binding site detection and
      identifies novel cis-regulatory sites in mammalian GABAA receptor subunit genes.
AB  - Understanding transcription factor (TF) mediated control of gene expression
      remains a major challenge at the interface of computational and experimental
      biology. Computational techniques predicting TF-binding site specificity are
      frequently unreliable. On the other hand, comprehensive experimental validation
      is difficult and time consuming. We introduce a simple strategy that dramatically
      improves robustness and accuracy of computational binding site prediction. First,
      we evaluate the rate of recurrence of computational TFBS predictions by commonly
      used sampling procedures. We find that the vast majority of results are
      biologically meaningless. However clustering results based on nucleotide position
      improves predictive power. Additionally, we find that positional clustering
      increases robustness to long or imperfectly selected input sequences. Positional
      clustering can also be used as a mechanism to integrate results from multiple
      sampling approaches for improvements in accuracy over each one alone. Finally, we
      predict and validate regulatory sequences partially responsible for
      transcriptional control of the mammalian type A gamma-aminobutyric acid receptor
      (GABA(A)R) subunit genes. Positional clustering is useful for improving
      computational binding site predictions, with potential application to improving
      our understanding of mammalian gene expression. In particular, predicted
      regulatory mechanisms in the mammalian GABA(A)R subunit gene family may open new
      avenues of research towards understanding this pharmacologically important
      neurotransmitter receptor system.

PMID- 17204487
TI  - Pulmonary rheumatoid nodules demonstrating features usually associated with
      rheumatoid synovial membrane.
AB  - OBJECTIVES: To describe the unusual immunohistological characteristics of two
      pulmonary rheumatoid nodules showing ectopic lymphoid follicles and the features
      normally associated with rheumatoid synovial membrane, and to discuss the
      implications of this novel observation. METHODS: Two formalin-fixed wax-embedded
      pulmonary rheumatoid nodules were processed for immunohistology. RESULTS: The
      central structure of the pulmonary nodules was typical of that uniformly expected
      in a rheumatoid nodule with central necrosis surrounded by a palisade of
      macrophages. However, a feature not previously observed in nodules was the
      presence of lymphoid aggregates containing B lymphocytes and, in some cases,
      showing characteristic features of lymphoid follicles. CONCLUSIONS: The presence
      of B lymphocytes and the development of ectopic lymphoid follicles in rheumatoid
      nodules have not been described previously. It is similar to synovial membrane,
      and contrasts with the expected structure of subcutaneous nodules where B cells
      and lymphoid follicles are normally absent. These observations establish that the
      morphology of rheumatoid nodules can vary in different tissues. They further
      suggest that the inflammatory process in the nodule and synovial membrane are
      likely to be similar, and that the characteristics of different tissues may be an
      important determinant of apparent differences between inflammatory lesions in
      synovial membrane and extra-articular nodules in rheumatoid arthritis.

PMID- 17204488
TI  - Microtubule- and actin filament-dependent motors are distributed on pollen tube
      mitochondria and contribute differently to their movement.
AB  - The pollen tube exhibits cytoplasmic streaming of organelles, which is dependent
      on the actin-myosin system. Although microtubule-based motors have also been
      identified in the pollen tube, many uncertainties exist regarding their role in
      organelle transport. As part of our attempt to understand the role of microtubule
      based movement in the pollen tube of tobacco, we investigated the cooperation
      between microtubules and actin filaments in the transport of mitochondria and
      Golgi vesicles, which are distributed differently in the growing pollen tube. The
      analysis was performed using in vitro motility assays in which organelles move
      along both microtubules and actin filaments. The results indicated that the
      movement of mitochondria and Golgi vesicles is slow and continuous along
      microtubules but fast and irregular along actin filaments. In addition, the
      presence of microtubules in the motility assays forces organelles to use lower
      velocities. Actin- and tubulin-binding tests, immunoblotting and immunogold
      labeling indicated that different organelles bind to identical myosins but
      associate with specific kinesins. We found that a 90 kDa kinesin (previously
      known as 90 kDa ATP-MAP) is associated with mitochondria but not with Golgi
      vesicles, whereas a 170 kDa myosin is distributed on mitochondria and other
      organelle classes. In vitro and in vivo motility assays indicate that
      microtubules and kinesins decrease the speed of mitochondria, thus contributing
      to their positioning in the pollen tube.

PMID- 17204489
TI  - Eye ultrastructure in the pollen-feeding beetle, Xanthochroa luteipennis
      (Coleoptera: Cucujiformia: Oedemeridae).
AB  - The pollen-consuming beetle Xanthochroa luteipennis, which belongs to the family
      Oedemeridae, possesses a nearly spherical eye of approximately 400 microm in
      diameter. The eye contains 750-800, mostly hexagonal ommatidia, which are of the
      acone apposition type and have an open rhabdom. A well-developed pupil mechanism
      controls the light flux to the rhabdom. The pupil is formed with the help of
      screening pigment translocations, involving primary and secondary (accessory)
      pigment cells. Cross-sections of rhabdoms reveal that they are developed as ring
      like structures, made up of the rhabdomeres of six retinula cells, surrounding a
      rod-like inner column of two fused rhabdomeres. Rhabdoms of ommatidia in the
      middle of the eye differ somewhat from those in more peripheral areas. In the
      former the central rhabdom is circular in cross-section, while in the latter it
      is spindle-shaped. The rhabdom organization in combination with the distal pupil
      mechanism is seen as an adaptation to maximize photon capture under a variety of
      ambient light intensities, for Oedemerid beetles are commonly active during the
      day as well as the night.

PMID- 17204490
TI  - How much gas does it take to pump up synaptic transmission in the brain?

PMID- 17204491
TI  - Understanding central fatigue: where to go?

PMID- 17204492
TI  - Daytime variability of baroreflex function in patients with obstructive sleep
      apnoea: implications for hypertension.
AB  - Obstructive events during sleep in patients with obstructive sleep apnoea (OSA)
      cause large alterations in blood pressure, and this may lead to changes in
      baroreflex function with implications for long-term blood pressure control. This
      study examined the daytime variations in the responses to carotid baroreceptor
      stimulation in OSA patients. We determined the cardiac and vascular responses
      every 3 h between 09.00 and 21.00 h in 20 patients with OSA, using graded
      suctions and pressures applied to a neck collar. These responses were plotted
      against estimated carotid sinus pressures and, from these plots, baroreflex
      sensitivities and operating points were taken as the maximal slopes and the
      corresponding carotid sinus pressures, respectively. We found that at 09.00 h,
      sensitivity for the control of vascular resistance was at its lowest (--1.2 +/-
      0.2% mmHg(-1), compared with --1.9 +/- 0.3% mmHg(-1) at 12.00 h, P < 0.02) and
      operating point for control of mean arterial pressure was at its highest (101.1
      +/- 5.8 mmHg, compared with 94.1 +/- 5.8 mmHg at 12.00 h, P < 0.05). This is in
      contrast to previous data from normal subjects, in whom sensitivity was highest
      and operating point lowest at 09.00 h. We suggest that the higher baroreflex
      sensitivity and lower operating point seen in the mornings in normal subjects may
      provide a protective mechanism against hypertension and that this protection is
      absent in patients with OSA. It is possible that the reduced reflex sensitivity
      and increased operating point in the mornings may actually promote hypertension.

PMID- 17204493
TI  - Prenatal corticosterone exposure results in altered AT1/AT2, nephron deficit and
      hypertension in the rat offspring.
AB  - Maternal treatment with the synthetic glucocorticoid, dexamethasone has been
      reported to result in a nephron deficit and development of hypertension in the
      offspring of rats. However, it is not known whether elevated maternal
      corticosterone (CORT), the natural glucocorticoid, has similar effects on blood
      pressure and nephron endowment. The present study investigated the effects of
      CORT (0.8 mg kg(-1) day(-1)) administration on embryonic day 14 (E14) and E15 of
      pregnancy on: (1) nephron number at postnatal day 30 (PN30); (2) blood pressure
      at PN120; and (3) receptors of the renal renin-angiotensin system (RRAS)
      (AT(1)Ra, AT(1)Rb and AT(2)Ra) during both embryonic (E16, E20) and adolescent
      (PN30) life. Plasma CORT concentrations were approximately doubled 30 min after
      injection. Unbiased stereological analysis revealed that maternal CORT treatment
      resulted in a nephron deficit of 21 and 19% in male and female offspring,
      respectively. Mean arterial pressures were significantly elevated in offspring of
      both sexes from the CORT group. Real-time PCR revealed that CORT treatment
      increased expression of AT(1)Ra and AT(2)R at E16, and at PN30. Expression of
      AT(1)Rb was downregulated in embryonic life but upregulated at PN30. We believe
      that these results are the first to demonstrate that maternal CORT treatment
      results in a nephron deficit and development of hypertension in the rat
      offspring. Changes in the RRAS may be contributing to these phenotypes.
      Critically, this study suggests that increased but physiological levels of the
      natural glucocorticoid can programme similar changes to those seen with
      pharmacological doses of the synthetic glucocorticoid. This may have important
      implications for women experiencing significant stress during pregnancy.

PMID- 17204494
TI  - Polycystin-2 cation channel function in the human syncytiotrophoblast is
      regulated by microtubular structures.
AB  - Polycystin-2 (PC2), encoded by PKD2, which is one of the genes whose mutations
      cause polycystic kidney disease, is abundantly produced in the apical domain of
      the syncytiotrophoblast (hST) of term human placenta. PC2, a TRP-type (TRPP2) non
      selective cation channel, is present in primary cilia of renal epithelial cells,
      a microtubule-based ancillary structure with sensory function. The hST has
      abundant cytoskeletal structures, and actin filament dynamics regulate PC2
      channel function in this epithelium. However, it is expected that the apical hST
      excludes microtubular structures. Here, we demonstrated by Western blot and
      immunocytochemical analyses that hST apical vesicles indeed contain microtubule
      structural components, including tubulin isoforms, acetylated alpha-tubulin, and
      the kinesin motor proteins KIF3A and KIF3B. PC2 and tubulin were substantially
      colocalized in hST vesicles. Treatment of hST vesicles with either the
      microtubular disrupter colchicine (15 microM) or the microtubular stabilizer
      paclitaxel (taxol, 15 microM) resulted in distinct patterns of microtubular re
      organization and PC2 redistribution. We also observed that changes in
      microtubular dynamics regulate PC2 channel function. Addition of colchicine
      rapidly inhibited PC2 channel activity in lipid-bilayer reconstituted hST
      membranes. Addition of either tubulin and GTP, or taxol, however, stimulated PC2
      channel activity in control hST membranes. Interestingly, we found that the
      kinesin motor protein KIF3A was capable of increasing PC2 channel activity in
      hST. We believe that the data are the first to provide a direct demonstration of
      a microtubular interaction with PC2 in the hST. This interaction thus plays an
      important regulatory role in the control of ion transport in the human placenta.

PMID- 17204495
TI  - Maternal taurine supplementation in the late pregnant rat stimulates postnatal
      growth and induces obesity and insulin resistance in adult offspring.
AB  - An adequate supply of taurine during fetal life is important for normal beta-cell
      development and insulin action. An altered availability of taurine may programme
      glucose metabolism in utero and result in type 2 diabetes in adult age. We
      examined whether maternal taurine supplementation in late pregnant rats affects
      postnatal growth, adult body composition, insulin sensitivity and endogenous
      insulin secretion in intrauterine growth restricted (IUGR) and normal offspring.
      Uterine artery ligation or sham operations were performed on gestational day (GD)
      19. Taurine supplementation was given to half of the dams from GD 18 until term,
      resulting in four groups of offspring: sham (n = 22), sham/taurine (n = 22), IUGR
      (n = 22) and IUGR/taurine (n = 24). The offspring were studied at 12 weeks of
      age. In offspring with normal birth weight, fetal taurine supplementation
      markedly stimulated postnatal growth. In sham/taurine females, fat depots, plasma
      free fatty acid and leptin concentrations were increased, and insulin sensitivity
      was reduced. Insulin sensitivity was unaltered in IUGR and IUGR/taurine
      offspring. However, whereas IUGR offspring showed little catch-up growth, 50% of
      IUGR/taurine animals displayed complete catch-up at 12 weeks of age, and these
      animals had increased fat depots and reduced insulin sensitivity. In conclusion,
      taurine supplementation in late gestation resulted in accelerated postnatal
      growth, which was associated with adult obesity and insulin resistance in both
      IUGR and normal offspring. This effect was particularly evident in females. These
      data suggest that fetal taurine availability is an important determinant for
      postnatal growth, insulin sensitivity and fat accumulation.

PMID- 17204496
TI  - Reversible inhibition of GABAA receptors by alpha7-containing nicotinic receptors
      on the vertebrate postsynaptic neurons.
AB  - Nicotinic acetylcholine receptors (nAChRs) are expressed throughout the central
      nervous system and influence a variety of higher order functions including
      learning and memory. While the effects of presynaptic nAChRs on transmitter
      release have been well documented, little is known about possible postsynaptic
      actions. A major species of neuronal nAChRs contains the alpha7 gene product and
      has a high relative permeability to calcium. Both on rodent hippocampal
      interneurons and on chick ciliary ganglion neurons these alpha7-nAChRs are often
      closely juxtaposed to GABAA receptors. We show here that in both cases activation
      of alpha7-nAChRs on the postsynaptic neuron acutely down-regulates GABA-induced
      currents. Nicotine application to dissociated ciliary ganglion neurons diminished
      subsequent GABAA receptor responses to GABA. The effect was blocked by alpha7
      nAChR antagonists, by chelation of intracellular Ca2+ with BAPTA, and by
      inhibition of both Ca2+-calmodulin-dependent protein kinase II and mitogen
      activated protein kinase. A similar outcome was obtained in the hippocampus where
      electrical stimulation to activate cholinergic fibres reduced the amplitude of
      subsequent GABAA receptor-mediated inhibitory postsynaptic currents. The
      reduction showed the same calcium and kinase dependence seen in ciliary ganglion
      neurons and was absent in hippocampal slices from alpha7-nAChR knockout mice.
      Moreover, alpha7-nAChR blockade in hippocampal slices reduced rundown of GABAA
      receptor-mediated whole-cell responses, indicating ongoing endogenous modulation.
      The results demonstrate regulation of GABAA receptors by alpha7-nAChRs on the
      postsynaptic neuron and identify a new mechanism by which nicotinic cholinergic
      signalling influences nervous system function.

PMID- 17204497
TI  - Thin-filament regulation of force redevelopment kinetics in rabbit skeletal
      muscle fibres.
AB  - Thin-filament regulation of isometric force redevelopment (k(tr)) was examined in
      rabbit psoas fibres by substituting native TnC with either cardiac TnC (cTnC), a
      site I-inactive skeletal TnC mutant (xsTnC), or mixtures of native purified
      skeletal TnC (sTnC) and a site I- and II-inactive skeletal TnC mutant (xxsTnC).
      Reconstituted maximal Ca(2+)-activated force (rF(max)) decreased as the fraction
      of sTnC in sTnC: xxsTnC mixtures was reduced, but maximal k(tr) was unaffected
      until rF(max) was <0.2 of pre-extracted F(max). In contrast, reconstitution with
      cTnC or xsTnC reduced maximal k(tr) to 0.48 and 0.44 of control (P < 0.01),
      respectively, with corresponding rF(max) of 0.68 +/- 0.03 and 0.25 +/- 0.02
      F(max). The k(tr)-pCa relation of fibres containing sTnC: xxsTnC mixtures
      (rF(max) > 0.2 F(max)) was little effected, though k(tr) was slightly elevated at
      low Ca(2+) activation. The magnitude of the Ca(2+)-dependent increase in k(tr)
      was greatly reduced following cTnC or xsTnC reconstitution because k(tr) at low
      levels of Ca(2+) was elevated and maximal k(tr) was reduced. Solution Ca(2+)
      dissociation rates (k(off)) from whole Tn complexes containing sTnC (26 +/- 0.1
      s(-1)), cTnC (38 +/- 0.9 s(-1)) and xsTnC (50 +/- 1.2 s(-1)) correlated with
      k(tr) at low Ca(2+) levels and were inversely related to rF(max). At low Ca(2+)
      activation, k(tr) was similarly elevated in cTnC-reconstituted fibres with ATP or
      when cross-bridge cycling rate was increased with 2-deoxy-ATP. Our results and
      model simulations indicate little or no requirement for cooperative interactions
      between thin-filament regulatory units in modulating k(tr) at any [Ca(2+)] and
      suggest Ca(2+) activation properties of individual troponin complexes may
      influence the apparent rate constant of cross-bridge detachment.

PMID- 17204498
TI  - Mucus secretion by single tracheal submucosal glands from normal and cystic
      fibrosis transmembrane conductance regulator knockout mice.
AB  - Submucosal glands line the cartilaginous airways and produce most of the
      antimicrobial mucus that keeps the airways sterile. The glands are defective in
      cystic fibrosis (CF), but how this impacts airway health remains uncertain.
      Although most CF mouse strains exhibit mild airway defects, those with the
      C57Bl/6 genetic background have increased airway pathology and susceptibility to
      Pseudomonas. Thus, they offer the possibility of studying whether, and if so how,
      abnormal submucosal gland function contributes to CF airway disease. We used
      optical methods to study fluid secretion by individual glands in tracheas from
      normal, wild-type (WT) mice and from cystic fibrosis transmembrane conductance
      regulator (CFTR) knockout mice (Cftr(m1UNC)/Cftr(m1UNC); CF mice). Glands from WT
      mice qualitatively resembled those in humans by responding to carbachol and
      vasoactive intestinal peptide (VIP), although the relative rates of VIP- and
      forskolin-stimulated secretion were much lower in mice than in large mammals. The
      pharmacology of mouse gland secretion was also similar to that in humans; adding
      bumetanide or replacement of HCO(3)(-) by Hepes reduced the carbachol response by
      approximately 50%, and this inhibition increased to 80% when both manoeuvres were
      performed simultaneously. It is important to note that glands from CFTR knockout
      mice responded to carbachol but did not secrete when exposed to VIP or forskolin,
      as has been shown previously for glands from CF patients. Tracheal glands from WT
      and CF mice both had robust secretory responses to electrical field stimulation
      that were blocked by tetrodotoxin. It is interesting that local irritation of the
      mucosa using chili pepper oil elicited secretion from WT glands but did not
      stimulate glands from CF mice. These results clarify the mechanisms of murine
      submucosal gland secretion and reveal a novel defect in local regulation of
      glands lacking CFTR which may also compromise airway defence in CF patients.

PMID- 17204500
TI  - The respiratory drive to thoracic motoneurones in the cat and its relation to the
      connections from expiratory bulbospinal neurones.
AB  - The descending control of respiratory-related motoneurones in the thoracic spinal
      cord remains the subject of some debate. In this study, direct connections from
      expiratory bulbospinal neurones to identified motoneurones were investigated
      using spike-triggered averaging and the strengths of connection revealed were
      related to the presence and size of central respiratory drive potentials in the
      same motoneurones. Intracellular recordings were made from motoneurones in
      segments T5-T9 of the spinal cord of anaesthetized cats. Spike-triggered
      averaging from expiratory bulbospinal neurones in the caudal medulla revealed
      monosynaptic EPSPs in all groups of motoneurones, with the strongest connections
      to expiratory motoneurones with axons in the internal intercostal nerve. In the
      latter, connection strength was similar irrespective of the target muscle (e.g.
      external abdominal oblique or internal intercostal) and the EPSP amplitude was
      positively correlated with the amplitude of the central respiratory drive
      potential of the motoneurone. For this group, EPSPs were found in 45/83
      bulbospinal neurone/motoneurone pairs, with a mean amplitude of 40.5 microV. The
      overall strength of the connection supports previous measurements made by cross
      correlation, but is about 10 times stronger than that reported in the only
      previous similar survey to use spike-triggered averaging. Calculations are
      presented to suggest that this input alone is sufficient to account for all the
      expiratory depolarization seen in the recorded motoneurones. However, extra
      sources of input, or amplification of this one, are likely to be necessary to
      produce a useful motoneurone output.

PMID- 17204499
TI  - Morphological and physiological evidence for interstitial cell of Cajal-like
      cells in the guinea pig gallbladder.
AB  - Gallbladder smooth muscle (GBSM) exhibits spontaneous rhythmic electrical
      activity, but the origin and propagation of this activity are not understood. We
      used morphological and physiological approaches to determine whether interstitial
      cells of Cajal (ICC) are present in the guinea pig extrahepatic biliary tree.
      Light microscopic studies involving Kit tyrosine kinase immunohistochemistry and
      laser confocal imaging of Ca(2+) transients revealed ICC-like cells in the
      gallbladder. One type of ICC-like cell had elongated cell bodies with one or two
      primary processes and was observed mainly along GBSM bundles and nerve fibres.
      The other type comprised multipolar cells that were located at the origin and
      intersection of muscle bundles. Electron microscopy revealed ICC-like cells that
      were rich in mitochondria, caveolae and smooth endoplasmic reticulum and formed
      close appositions between themselves and with GBSM cells. Rhythmic Ca(2+)
      flashes, which represent Ca(2+) influx during action potentials, were
      synchronized in any given GBSM bundle and associated ICC-like cells. Gap junction
      uncouplers (1-octanol, carbenoxolone, 18beta-glycyrrhetinic acid and connexin
      mimetic peptide) eliminated or greatly reduced Ca(2+) flashes in GBSM, but they
      persisted in ICC-like cells, whereas the Kit tyrosine kinase inhibitor, imanitib
      mesylate, eliminated or reduced action potentials and Ca(2+) flashes in both cell
      types, as well as associated tissue contractions. This study provides
      morphological and physiological evidence for the existence of ICC-like cells in
      the gallbladder and presents data supporting electrical coupling between ICC-like
      and GBSM cells. The results support a role for ICC-like cells in the generation
      and propagation of spontaneous rhythmicity, and hence, the excitability of
      gallbladder.

PMID- 17204501
TI  - C-type natriuretic peptide activates a non-selective cation current in acutely
      isolated rat cardiac fibroblasts via natriuretic peptide C receptor-mediated
      signalling.
AB  - In the heart, fibroblasts play an essential role in the deposition of the
      extracellular matrix and they also secrete a number of hormonal factors. Although
      natriuretic peptides, including C-type natriuretic peptide (CNP) and brain
      natriuretic peptide, have antifibrotic effects on cardiac fibroblasts, the
      effects of CNP on fibroblast electrophysiology have not been examined. In this
      study, acutely isolated ventricular fibroblasts from the adult rat were used to
      measure the effects of CNP (2 x 10(-8) M) under whole-cell voltage-clamp
      conditions. CNP, as well as the natriuretic peptide C receptor (NPR-C) agonist
      cANF (2 x 10(-8) M), significantly increased an outwardly rectifying non
      selective cation current (NSCC). This current has a reversal potential near 0 mV.
      Activation of this NSCC by cANF was abolished by pre-treating fibroblasts with
      pertussis toxin, indicating the involvement of G(i) proteins. The cANF-activated
      NSCC was inhibited by the compounds Gd(3+), SKF 96365 and 2-aminoethoxydiphenyl
      borate. Quantitative RT-PCR analysis of mRNA from rat ventricular fibroblasts
      revealed the expression of several transient receptor potential (TRP) channel
      transcripts. Additional electrophysiological analysis showed that U73122, a
      phospholipase C antagonist, inhibited the cANF-activated NSCC. Furthermore, the
      effects of CNP and cANF were mimicked by the diacylglycerol analogue 1-oleoyl-2
      acetyl-sn-glycerol (OAG), independently of protein kinase C activity. These are
      defining characteristics of specific TRPC channels. More detailed molecular
      analysis confirmed the expression of full-length TRPC2, TRPC3 and TRPC5
      transcripts. These data indicate that CNP, acting via the NPR-C receptor,
      activates a NSCC that is at least partially carried by TRPC channels in cardiac
      fibroblasts.

PMID- 17204502
TI  - Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel
      (ASIC) 1a.
AB  - The homomeric acid-sensing ion channel 1a (ASIC1a) is a H+-activated ion channel
      with important physiological functions and pathophysiological impact in the
      central nervous system. Here we show that homomeric ASIC1a is distinguished from
      other ASICs by a reduced response to successive acid stimulations. Such a reduced
      response is called tachyphylaxis. We show that tachyphylaxis depends on H+
      permeating through ASIC1a, that tachyphylaxis is attenuated by extracellular
      Ca2+, and that tachyphylaxis is probably linked to Ca2+ permeability of ASIC1a.
      Moreover, we provide evidence that tachyphylaxis is probably due to a long-lived
      inactive state of ASIC1a. A deeper understanding of ASIC1a tachyphylaxis may lead
      to pharmacological control of ASIC1a activity that could be of potential benefit
      for the treatment of stroke.

PMID- 17204503
TI  - Breathing dysfunctions associated with impaired control of postinspiratory
      activity in Mecp2-/y knockout mice.
AB  - Rett syndrome (RTT) is an inborn neurodevelopmental disorder caused by mutations
      in the X-linked methyl-CpG binding protein 2 gene (MECP2). Besides mental
      retardation, most patients suffer from potentially life-threatening breathing
      arrhythmia. To study its pathophysiology, we performed comparative analyses of
      the breathing phenotype of Mecp2-/y knockout (KO) and C57BL/6J wild-type mice
      using the perfused working heart-brainstem preparation (WHBP). We simultaneously
      recorded phrenic and efferent vagal nerve activities to analyse the motor pattern
      of respiration, discriminating between inspiration, postinspiration and late
      expiration. Our results revealed respiratory disturbances in KO preparations that
      were similar to those reported from in vivo measurements in KO mice and also to
      those seen in RTT patients. The main finding was a highly variable
      postinspiratory activity in KO mice that correlated closely with breathing
      arrhythmias leading to repetitive apnoeas even under undisturbed control
      conditions. Analysis of the pontine and peripheral sensory regulation of
      postinspiratory activity in KO preparations revealed: (i) prolonged apnoeas
      associated with enhanced postinspiratory activity after glutamate-induced
      activation of the pontine Kolliker-Fuse nucleus; and (ii) prolonged apnoeas and
      lack of reflex desensitization in response to repetitive vagal stimulations. We
      conclude that impaired network and sensory mediated synaptic control of
      postinspiration induces severe breathing dysfunctions in Mecp2-/y KO
      preparations. As postinspiration is particularly important for the control of
      laryngeal adductors, the finding might explain the upper airway-related clinical
      problems of patients with RTT such as apnoeas, loss of speech and weak
      coordination of breathing and swallowing.

PMID- 17204504
TI  - Intravascular ADP and soluble nucleotidases contribute to acute prothrombotic
      state during vigorous exercise in humans.
AB  - Extracellular ATP and ADP trigger vasodilatatory and prothrombotic signalling
      events in the vasculature. Here, we tested the hypothesis that nucleotide
      turnover is activated in the bloodstream of exercising humans thus contributing
      to the enhanced platelet reactivity and haemostasis. Right atrial, arterial and
      venous blood samples were collected from endurance-trained athletes at rest,
      during submaximal and maximal cycle ergometer exercise, and after early recovery.
      ATP-specific bioluminescent assay, together with high-performance liquid
      chromatographic analysis, revealed that plasma ATP and ADP concentrations
      increased up to 2.5-fold during maximal exercise. Subsequent flow cytometric
      analysis showed that plasma from exercising subjects significantly up-regulated
      the surface expression of P-selectin in human platelets and these prothrombotic
      effects were diminished after scavenging plasma nucleotides with exogenous
      apyrase. Next, using thin layer chromatographic assays with [gamma-(32)P]ATP and
      (3)H/(14)C-labelled nucleotides, we showed that two soluble nucleotide
      inactivating enzymes, nucleotide pyrophosphatase/phosphodiesterase and nucleoside
      triphosphate diphosphohydrolase, constitutively circulate in human bloodstream.
      Strikingly, serum nucleotide pyrophosphatase and hydrolase activities rose during
      maximal exercise by 20-25 and 80-100%, respectively, and then declined after 30
      min recovery. Likewise, soluble nucleotidases were transiently up-regulated in
      the venous blood of sedentary subjects during exhaustive exercise. Human serum
      also contains 5'-nucleotidase, adenylate kinase and nucleoside diphosphate (NDP)
      kinase; however, these activities remain unchanged during exercise. In
      conclusion, intravascular ADP significantly augments platelet activity during
      strenuous exercise and these prothrombotic responses are counteracted by
      concurrent release of soluble nucleotide-inactivating enzymes. These findings
      provide a novel insight into the mechanisms underlying the enhanced risk of
      occlusive thrombus formation under exercising conditions.

PMID- 17204506
TI  - Prognostic significance of tumor necrosis in primary transitional cell carcinoma
      of upper urinary tract.
AB  - OBJECTIVE: We investigated the prognostic significance of tumor necrosis in
      primary transitional cell carcinoma (TCC) of upper urinary tract. METHODS: We
      retrospectively analyzed the records of 119 patients who received surgical
      management for primary TCC of upper urinary tract. The presence or absence of
      tumor necrosis was evaluated based on the macroscopic description of the tumor.
      Along with pathologic features of tumor necrosis, we assessed the impacts of
      various prognostic factors previously reported for TCC of upper urinary tract.
      RESULTS: Tumor necrosis was identified in 19 (16.0%) patients. Patients with
      tumor necrosis were more likely to have higher local stage, nodal involvement,
      higher tumor grade, lymphovascular invasion (LVI), and recurrence of disease.
      Among all subjects, disease-specific survival rates at 5 years after surgery for
      patients with and without macroscopic tumor necrosis were 36.7 and 83.2%,
      respectively (P = 0.0001). In multivariate analysis, only pathologic T stage, LVI
      and tumor necrosis were shown to be independent predictors for disease-specific
      survival. For solely the invasive tumors, variables including age, surgical
      margin and tumor necrosis were observed to be independent prognostic factors for
      disease-specific survival in multivariate analysis, with tumor necrosis showing
      the highest rank order of statistical significance. CONCLUSIONS: Our results
      suggest that macroscopic tumor necrosis may be a useful prognostic indicator for
      primary TCC of upper urinary, especially for invasive tumors. Further
      investigation would be warranted for the prognostic implications of tumor
      necrosis in TCCs of upper urinary tract and on actual pathogenesis of tumor
      necrosis in upper tract TCC.

PMID- 17204505
TI  - GABA excitation in mouse hilar neuropeptide Y neurons.
AB  - Neuropeptide Y-containing interneurons in the dentate hilar area play an
      important role in inhibiting the activity of hippocampal circuitry. Hilar cells
      are often among the first lost in hippocampal epilepsy. As many types of neurons
      are found in the hilus, we used a new transgenic mouse expressing green
      fluorescent protein (GFP) in a subset of neurons that colocalized neuropeptide Y
      (NPY), somatostatin (SST), and GABA for whole-cell, perforated, and cell-attached
      recording in 240 neurons. As these neurons have not previously been identifiable
      in live slices, they have not been the focus of physiological analysis. Hilar NPY
      neurons showed modest spike frequency adaptation, a large 15.6 +/- 1.0 mV
      afterhyperpolarization, a mean input resistance of 335 +/- 26 M Omega, and were
      capable of fast-firing. Muscimol-mediated excitatory actions were found in a
      nominally Ca(2+)-free/high-Mg(2+) bath solution using cell-attached recording.
      GABA(A) receptor antagonists inhibited half the recorded neurons and blocked
      burst firing. Gramicidin perforated-patch recording revealed a GABA reversal
      potential positive to both the resting membrane potential and spike threshold.
      Together, these data suggest GABA is excitatory to many NPY cells. NPY and SST
      consistently hyperpolarized and reduced spike frequency in these neurons. No
      hyperpolarization of NPY on membrane potential was detected in the presence of
      tetrodotoxin, AP5, CNQX and bicuculline, supporting an indirect effect. Under
      similar conditions, SST hyperpolarized the cells, suggesting a direct
      postsynaptic action. Depolarizing actions of GABA and GABA-dependent burst-firing
      may synchronize a rapid release of GABA, NPY, and SST, leading to pre- and
      postsynaptic inhibition of excitatory hippocampal circuits.

PMID- 17204507
TI  - Phase II study of radiation therapy combined with weekly nedaplatin in locally
      advanced uterine cervical carcinoma: Kitasato Gynecologic Radiation Oncology
      Group (KGROG 0501).
AB  - In order to evaluate the safety and efficacy of chemoradiotherapy using
      nedaplatin for locally advanced uterine cervical carcinoma in Japanese patients,
      we have started a single-institute phase II trial. Eligibility criteria include:
      (i) pathologically proven squamous cell carcinoma or adenocarcinoma, (ii)
      clinical FIGO stage Ib, IIa, or IIb with bulky tumor (> 40 mm) or pelvic lymph
      node swelling, or (iii) clinical FIGO stage IIIa, IIIb and IVa, (iv) no para
      aortic lymph node swelling. A combination of external beam radiation and high
      dose rate intracavitary irradiation is given. Nedaplatin (30 mg/m2) is
      intravenously infused on a weekly basis for five times. The primary endpoint is 3
      year overall survival, and the secondary endpoints are tumor response, 2-year
      overall survival, 3-year progression-free survival, acute adverse events,
      protocol treatment compliance, and late adverse events. We plan to recruit 45
      patients within 3 years.

PMID- 17204508
TI  - Spread of Enterobacteriaceae carrying the PER-1 extended-spectrum beta-lactamase
      gene as a chromosomal insert: a report from Italy.

PMID- 17204509
TI  - Understanding women's knowledge of breast cancer screening.

PMID- 17204510
TI  - Measuring young people's attitudes to breastfeeding using the Theory of Planned
      Behaviour.
AB  - BACKGROUND: The focus of this study was to design and pilot a questionnaire to
      measure young people's attitudes to breastfeeding using the Theory of Planned
      Behaviour (TPB). This is intended for subsequent use in a large-scale attitude
      survey, which in turn will inform the design of a breastfeeding intervention
      programme with adolescents. METHODS: The first three phases of a research
      programme employing the theory are described: belief elicitation, questionnaire
      development and a pilot study. Firstly, an elicitation study to identify the
      modal salient beliefs underlying young peoples' motivations to breastfeed, using
      six semi-structured focus groups with 48 young people, was performed. Secondly,
      the measurement instrument was constructed, incorporating all the key theoretical
      constructs and both direct and belief-based measures. The questionnaire was then
      piloted on a sample of 121 female and male schoolchildren to identify and assess
      the relative importance of the determinants of breastfeeding intention. RESULTS:
      The questionnaire proved to be reliable, and preliminary analysis provided strong
      support for the predictive power of the TPB. CONCLUSIONS: Some key issues
      involved in the operationalization of the theory are highlighted, which may be of
      interest to researchers involved in the design of TPB questionnaires for use in
      other intervention programmes.

PMID- 17204512
TI  - Wilhelm Weinberg's 1913 Large Retrospective Cohort Study: a rediscovery.
AB  - Wilhelm Weinberg, German physician, founder, and president of the Stuttgart
      Society for Racial Hygiene, published in 1913 the results of a large,
      retrospective cohort study entitled Die Kinder der Tuberkuloesen (Children of the
      Tuberculous). The exposed cohort comprised 18,212 children whose 3,246 fathers
      and 2,022 mothers died of tuberculosis between 1873 and 1902. The unexposed
      cohort comprised 7,574 children whose 1,830 parents died of causes other than
      tuberculosis in 1876, 1879, or 1886. He found that children of tuberculous
      parents had higher mortality rates and lower fertility than did children of
      nontuberculous parents. Because of its size, rigorous design, and meticulous
      analysis, Weinberg's cohort study stands as one of the major epidemiologic works
      carried out before 1945.

PMID- 17204513
TI  - Areca nut chewing and mortality in an elderly cohort study.
AB  - Compared with the well-documented association with betel-related cancer, little
      is known about the long-term effect of areca nut chewing on other fatal diseases.
      The authors' analyses were based on a population-based cohort study in Taiwan,
      including 4,049 participants aged 60 years or older enrolled in 1989 and 2,462
      participants aged 50-66 years enrolled in 1996. Information regarding betel quid
      chewing and covariates was collected at baseline and was updated at subsequent
      interviews. Proportional hazards analysis was performed to determine the effect
      of chewing on all-cause and cause-specific deaths. During a mean follow-up of 9.5
      years, 2,309 deaths occurred. Ever chewers were at higher risk of only total
      (hazard ratio = 1.19, 95% confidence interval: 1.05, 1.35) and cerebrovascular
      (hazard ratio = 1.66, 95% confidence interval: 1.19, 2.30) deaths. Furthermore,
      increased chewing-years or quid-years appeared to be associated with increased
      mortality risk (linear trend: p = 0.02 for total mortality and p = 0.001 for
      cerebrovascular mortality). The authors found that, although betel quid chewing
      resulted in a statistically significant increase in the risk of total and
      cerebrovascular deaths in the elderly population, the associations were weak and
      should be interpreted with caution. Further studies are needed to confirm these
      findings and to better understand the possible mechanisms of death.

PMID- 17204514
TI  - Measures of cumulative exposure from a standardized sun exposure history
      questionnaire: a comparison with histologic assessment of solar skin damage.
AB  - Ultraviolet radiation exposure is the dominant environmental determinant of all
      major forms of skin cancer; however, the nature of the association is
      incompletely understood. Existing instruments to capture sun exposure history
      tend to yield reproducible results, but the validity of these responses is
      unknown. To address this question, the authors examined the relation between
      responses to a standardized sun exposure instrument and histologic evidence of
      actinic damage in a population-based study of keratinocyte cancers from New
      Hampshire diagnosed from July 1, 1997, through March 31, 2000. A single study
      dermatopathologist histologically reviewed the adjacent skin of 925 skin cancer
      biopsies for the presence of solar keratoses and the extent of solar elastosis.
      The authors compared these measures with responses to a personal interview on
      history of sunburns, sunbathing, and time spent outdoors. Focusing on site
      specific exposure, they found variables that estimated cumulative exposure
      related to histologic evidence of actinic damage. In contrast, measures of
      acute/intermittent exposure were generally unrelated to solar damage
      histologically. Findings suggest that cumulative, but not intermittent, measures
      of sun exposure derived from a personal interview appear to reflect a person's
      exposure history based on histologic evidence.

PMID- 17204515
TI  - Alcohol consumption and breast cancer risk in the Women's Health Study.
AB  - The authors assessed the association between moderate alcohol consumption and
      breast cancer risk in the Women's Health Study (United States, 1992-2004). During
      an average of 10 years of follow-up, 1,484 cases of total breast cancer (1,190
      invasive and 294 in situ) were documented among 38,454 women who, at baseline,
      were free of cancer and cardiovascular disease and provided detailed dietary
      information, including alcohol consumption, for the preceding 12 months. Higher
      alcohol consumption was associated with a modest increase in breast cancer risk;
      the multivariable relative risks for > or =30 g/day of alcohol vs. none were 1.32
      (95% confidence interval (CI): 0.96, 1.82) for total breast cancer and 1.43 (95%
      CI: 1.02, 2.02) for invasive breast cancer. An increased risk was limited to
      estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors; the
      multivariable relative risks for an increment of 10 g/day of alcohol were 1.11
      (95% CI: 1.03, 1.20) for ER+PR+ tumors (804 cases), 1.00 (95% CI: 0.81, 1.24) for
      ER+PR- tumors (125 cases), and 0.99 (95% CI: 0.82, 1.20) for ER-PR- tumors (167
      cases). The association also seemed strongest among those taking postmenopausal
      hormones currently, but the test for interaction was not significant. The
      findings from this prospective study suggest that moderate alcohol consumption
      increases breast cancer risk.

PMID- 17204516
TI  - A prospective cohort study of bladder cancer risk in relation to active cigarette
      smoking and household exposure to secondhand cigarette smoke.
AB  - Active cigarette smoking is a major risk factor for bladder cancer. Secondhand
      exposure to cigarette smoke may also contribute to bladder carcinogenesis. The
      authors conducted a prospective cohort study to examine the influence of both
      active smoking and household exposure to secondhand smoke (SHS) on subsequent
      bladder cancer risk. The study population included persons from two cohorts
      established from private censuses conducted in Washington County, Maryland, in
      1963 (n = 45,749; 93 cases) and 1975 (n = 48,172; 172 cases). Poisson regression
      models were fitted to estimate the relative risk of bladder cancer associated
      with active and passive smoke exposure in the two cohorts (referent category:
      never smokers who did not live with any smokers). Current smokers had an elevated
      risk of bladder cancer in both the 1963 cohort (relative risk (RR) = 2.7, 95%
      confidence limits (CL): 1.6, 4.7) and the 1975 cohort (RR = 2.6, 95% CL: 1.7,
      3.9) after adjustment for age, education, and marital status. Among nonsmoking
      women, current household SHS exposure was associated with bladder cancer risk in
      the 1963 cohort (RR = 2.3, 95% CL: 1.0, 5.4) but not in the 1975 cohort (RR =
      0.9, 95% CL: 0.4, 2.3). This study further solidifies the evidence that active
      smoking is causally associated with bladder cancer. Additional studies are needed
      to determine whether passive smoking is a risk factor for bladder cancer.

PMID- 17204517
TI  - Risks of convulsion and aseptic meningitis following measles-mumps-rubella
      vaccination in the United Kingdom.
AB  - Measles-mumps-rubella (MMR) vaccines containing the Urabe strain of mumps were
      withdrawn in the United Kingdom in 1992 following demonstration of an increased
      risk of aseptic meningitis 15-35 days after vaccination. Following introduction
      of a replacement MMR vaccine (Priorix; GlaxoSmithKline, London, United Kingdom)
      in 1998, active surveillance of aseptic meningitis and convulsion was established
      to evaluate the risk associated with the new vaccine. No laboratory-confirmed
      cases of mumps meningitis were detected among children aged 12-23 months after
      administration of 1.6 million doses of Priorix (upper 95% confidence limit of
      risk: 1:437,000) in England and Wales. The upper 95% confidence limit excluded
      the risk found for mumps meningitis with Urabe vaccines (1:143,000 doses). No
      cases of aseptic meningitis were detected among children aged 12-23 months, who
      had received over 99,000 doses of Priorix (upper 95% confidence limit of risk:
      1:27,000), in a regional database of hospital-admitted cases. This compares with
      an observed risk of 1:12,400 for Urabe vaccines. An elevated relative incidence
      of convulsion was found in the 6- to 11-day period after receipt of Priorix
      (relative incidence = 6.26, 95% confidence interval: 3.85, 10.18)-consistent with
      the known effects of the measles component of MMR vaccine-but not in the 15- to
      35-day period (relative incidence = 1.48, 95% confidence interval: 0.88, 2.50) as
      occurred with Urabe-containing vaccines. This study demonstrates the power of
      active postmarketing surveillance to identify or exclude events too rare to be
      detected in prelicensure trials.

PMID- 17204518
TI  - Cigarette smoking, familial hematopoietic cancer, hair dye use, and risk of
      t(14;18)-defined subtypes of non-Hodgkin's lymphoma.
AB  - Some evidence suggests that smoking, a family history of hematopoietic cancer,
      and use of hair dyes are associated with t(14;18)-defined subsets of non
      Hodgkin's lymphoma (NHL) in men. To further evaluate these associations and to
      expand them to women, the authors determined t(14;18)(q32;q21) status by
      fluorescence in situ hybridization in 172 of 175 tumor blocks from a population
      based case-control study conducted in Nebraska during 1983-1986. Exposures in 65
      t(14;18)-positive cases and 107 t(14;18)-negative cases were compared with those
      among 1,432 controls. Odds ratios and 95% confidence intervals were calculated
      using polytomous logistic regression. Among men, smoking was not associated with
      risk of t(14;18)-positive or -negative NHL. Among women who had ever smoked
      cigarettes, there was an association with risk of t(14;18)-negative NHL (odds
      ratio (OR) = 1.9, 95% confidence interval (CI): 1.1, 3.3) but not t(14;18)
      positive NHL (p-difference = 0.01). The risks for t(14;18)-negative NHL among
      women increased with longer duration (>30 years: OR = 2.1, 95% CI: 1.1, 4.1) and
      early initiation (age </=20 years: OR = 2.2, 95% CI: 1.1, 4.4) of smoking. A
      family history of hematopoietic cancer was associated with a twofold higher risk
      for both t(14;18)-defined NHL subtypes among men and women. Hair dye use was not
      associated with either subtype. These findings should be interpreted cautiously
      because of the small sample.

PMID- 17204519
TI  - Long-term health outcomes associated with detectable troponin I concentrations.
AB  - BACKGROUND: Recent data suggest that older men with detectable cardiac troponin I
      (cTnI) concentrations that remain below the 99th percentile concentration cutoff
      are at increased risk for subsequent cardiovascular events. We designed this
      study to extend this observation by examining risk prediction in both men and
      women presenting to an emergency department with chest discomfort. METHODS: We
      obtained data for all-cause mortality and hospital discharges associated with
      either acute myocardial infarction (AMI) or congestive heart failure (CHF) for up
      to 8 years after the initial presentation in 448 patients who originally
      presented in 1996 with acute coronary syndrome (ACS). We performed retrospective
      analysis for cTnI (AccuTnI; Beckman Coulter) in frozen plasma samples based on
      the patients' reported time from onset of symptoms. Peak cTnI concentration was
      used for risk assessment. RESULTS: Patients with cTnI concentrations > or =0.02
      microg/L (i.e., limit of detection), including those whose peak values remained
      below the 99th percentile (0.04 microg/L), were at greater risk for death and
      AMI/CHF readmissions at 2, 5, and 8 years of follow-up compared with those with
      peak cTnI <0.02 microg/L. All results were statistically significant (P <0.05)
      except for death within 2 years among patients with normal but detectable cTnI
      (0.02 to 0.03 microg/L), relative to the group with values <0.02 microg/L. Kaplan
      Meier analyses indicated that both men and women with cTnI > or =0.02 microg/L
      had worse outcomes (P <0.001). CONCLUSION: Both men and women who present with
      possible ACS with detectable cTnI concentrations that remain below the 99th
      percentile are at a greater risk for future adverse events.

PMID- 17204520
TI  - Revisiting sugar-fat mixtures: sweetness and creaminess vary with phenotypic
      markers of oral sensation.
AB  - Genetic variation in oral sensation presumably influences ingestive behaviors
      through sensations arising from foods and beverages. Here, we investigated the
      influence of taste phenotype [6-n-propylthiouracil (PROP) bitterness, fungiform
      papillae (FP) density] on sweet and creamy sensations from sugar/fat mixtures.
      Seventy-nine subjects (43 males) reported the sweetness and creaminess of water
      or milk (skim, whole, heavy cream) varying in sucrose (0-20% w/v) on the general
      Labeled Magnitude Scale. Sweetness grew with sucrose concentration and when
      shifting from water to milk mixtures--the growth was greatest for those tasting
      PROP as most bitter. At higher sucrose levels, increasing fat blunted the PROP
      sweet relationship, whereas at lower levels, the relationship was effectively
      eliminated. Perceived sweetness of the mixture exceeded that predicted from the
      sum of components at low sucrose concentrations (especially for those tasting
      PROP most bitter) but fell below predicted at high concentrations, irrespective
      of fat level. Creaminess increased greatly with fat level and somewhat with
      sucrose. Those tasting PROP most bitter perceived greater creaminess in the heavy
      cream across all sucrose levels. Perceived creaminess was somewhat lower than
      predicted, irrespective of PROP bitterness. The FP density generally showed
      similar effects as PROP on sweetness and creaminess, (but to a lesser degree) and
      revealed potential taste-somatosensory interactions in weakly sweet stimuli.
      These data support that taste phenotype affects the nature of enhancement or
      suppression of sweetness and creaminess in liquid fat/sugar mixtures. Taste
      phenotype effects on sweetness and creaminess likely involve differential taste,
      retronasal olfactory, and somatosensory contributions to these perceptual
      experiences.

PMID- 17204521
TI  - Asymmetric suppression of components in binary aldehyde mixtures: behavioral
      studies in the laboratory rat.
AB  - The aim of the present study was to assess component interaction in the
      perception of the 2 aldehydes butanal and heptanal when presented in binary
      mixtures to rats. A further aim was to develop a behavioral paradigm for testing
      suppression of components in mixtures using rodent subjects. Thirsty rats were
      initially trained to discriminate between the 2 aldehydes butanal and heptanal in
      an olfactometer using a go/no-go discrimination task. This involved rats learning
      to place their noses in a sniff port where odors were presented and to lick a
      tube for water reward when one of the aldehydes was presented (S+) while
      withholding licking at the tube to the other, unrewarded, aldehyde (S-). A
      mixture condition was then introduced into the task, whereby a proportion of
      trials involved presentation of a combination of the 2 aldehydes as an additional
      unrewarded condition. Rats readily learned to withhold licking on trials when the
      mixture was presented. The concentration of the nonrewarded (S-) aldehyde in the
      mixture was then systematically decreased, whereas the concentration of the S+
      component was held constant. This eventually caused the S+ component in the
      mixture to suppress detection of the S-, as shown by an increasing number of lick
      responses (false alarms) on trials when the mixture was presented. These
      suppressing effects occurred well above the detection threshold for the S-
      aldehyde presented alone. Results showed asymmetric suppression in the mixture
      condition such that butanal suppressed detection of heptanal at much lower
      concentrations than vice versa. A second experiment showed that when both butanal
      and heptanal were present in a binary mixture at the same concentration (10(-6)
      volume %), then rats responded to the mixture as if only butanal was present.
      These findings are discussed in terms of butanal having higher mobility and being
      able to compete more effectively than heptanal for occupation of shared receptor
      sites.

PMID- 17204522
TI  - Amelioration of insulin resistance in women with PCOS via reduced insulin
      receptor substrate-1 Ser312 phosphorylation following laparoscopic ovarian
      electrocautery.
AB  - BACKGROUND: Increased Ser(312) phosphorylation of insulin receptor substrate
      (IRS)-1 is one possible molecular mechanism of insulin resistance in polycystic
      ovary syndrome (PCOS). We investigated whether laparoscopic ovarian
      electrocautery (LOE) improved insulin sensitivity in women with PCOS and examined
      the underlying molecular mechanism of LOE. METHODS: Adipose tissue and blood
      samples from 12 women with PCOS before, and 3 months after, LOE were analysed.
      RESULTS: Before LOE, women with PCOS were found to have significantly higher 2 h
      glucose, fasting and 2 h insulin levels, homeostasis model insulin resistance
      index and lower fasting glucose-to-insulin ratio (G(0)/I(0)) than healthy, lean,
      age-matched controls. Serum levels of glucose and insulin were significantly
      decreased, and G(0)/I(0) ratio was significantly increased 3 months after LOE.
      Levels of activated extracellular signal-regulated kinase 1/2 in PCOS women were
      higher than in controls, but were significantly decreased after LOE. Levels of
      insulin receptor, glucose transporter-4 and phosphatidylinositol 3-kinase were
      lower in PCOS patients before LOE than in controls and increased after LOE.
      Levels of Ser(312)-phosphorylated IRS-1 in PCOS women before LOE were higher than
      in controls and decreased significantly after LOE, whereas IRS-1 tyrosine
      phosphorylation in PCOS women before LOE was lower than in controls and increased
      significantly after LOE. CONCLUSION: Over the short observation period of this
      study, our results demonstrated that LOE effectively ameliorated insulin
      resistance in women with PCOS via decreased IRS-1 Ser(312) phosphorylation.

PMID- 17204523
TI  - Characterization and depletion of leukocytes from cells isolated from the pre
      ovulatory ovarian follicle.
AB  - BACKGROUND: Cells isolated from the periovulatory ovarian follicle are often used
      as a model of ovarian steroidogenesis and corpus luteum formation. The follicular
      fluid-derived cell (FFDC) population is, however, heterogeneous and in addition
      to granulosa-lutein cells, non-steroidogenic cells are also present. These non
      steroidogenic cells, especially the immune cells, may have important biological
      functions in this model. Here, we describe a method to isolate FFDC, characterize
      the phenotype of the immune cells and deplete immune cells from FFDC. METHODS AND
      RESULTS: Follicular fluid aspirated transvaginally during IVF was clarified by
      centrifugation and enzymatic dispersion, labelled for leukocyte-specific markers
      and analysed by flow cytometry. Leukocytes constituted 22% of FFDC and expressed
      macrophage/dendritic cell, monocyte and lymphocyte markers. Leukocytes were
      depleted with anti-CD45-conjugated immunobeads, resulting in an FFDC population
      with <1.9% leukocytes. Leukocyte-containing FFDC secreted more interleukin-8 in
      culture than leukocyte-depleted FFDC. CONCLUSION: Leukocyte-depleted FFDC may
      serve as a useful model to study the interaction of immune cells and luteinizing
      cells during corpus luteum formation.

PMID- 17204525
TI  - Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the
      human preimplantation embryo: a randomized controlled trial.
AB  - BACKGROUND: To test whether ovarian stimulation for in-vitro fertilization (IVF)
      affects oocyte quality and thus chromosome segregation behaviour during meiosis
      and early embryo development, preimplantation genetic screening of embryos was
      employed in a prospective, randomized controlled trial, comparing two ovarian
      stimulation regimens. METHODS: Infertile patients under 38 years of age were
      randomly assigned to undergo a mild stimulation regimen using gonadotrophin
      releasing hormone (GnRH) antagonist co-treatment (67 patients), which does not
      disrupt secondary follicle recruitment, or a conventional high-dose exogenous
      gonadotrophin regimen and GnRH agonist co-treatment (44 patients). Following IVF,
      embryos were biopsied at the eight-cell stage and the copy number of 10
      chromosomes was analysed in 1 or 2 blastomeres. RESULTS: The study was terminated
      prematurely, after an unplanned interim analysis (which included 61% of the
      planned number of patients) found a lower embryo aneuploidy rate following mild
      stimulation. Compared with conventional stimulation, significantly fewer oocytes
      and embryos were obtained following mild stimulation (P < 0.01 and < 0.05,
      respectively). Consequently, both regimens generated on average a similar number
      (1.8) of chromosomally normal embryos. Differences in rates of mosaic embryos
      suggest an effect of ovarian stimulation on mitotic segregation errors.
      CONCLUSIONS: Future ovarian stimulation strategies should avoid maximizing oocyte
      yield, but aim at generating a sufficient number of chromosomally normal embryos
      by reduced interference with ovarian physiology.

PMID- 17204524
TI  - Collagen gel contractility is enhanced in human endometriotic stromal cells: a
      possible mechanism underlying the pathogenesis of endometriosis-associated
      fibrosis.
AB  - BACKGROUND: Excessive fibrosis is frequently associated with endometriosis. To
      evaluate the involvement of the extracellular matrix contractility of
      endometriotic stromal cells (ECSCs) in the pathogenesis of endometriosis
      associated fibrosis, we compared the collagen gel contractility of cultured ECSCs
      with that of normal endometrial stromal cells. To clarify the mechanism
      underlying collagen gel contraction by ECSCs, we also evaluated the effect of (+)
      (R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride,
      monohydrate (Y-27632), a selective Rho-associated coiled-coil-forming protein
      kinase (ROCK) inhibitor, on the collagen gel contraction by ECSCs. METHODS AND
      RESULTS: ECSCs showed enhanced collagen gel contractility in comparison with
      NESCs. Myofibroblastic differentiation and the increased expression of
      fibronectin, RhoA, ROCK-I and ROCK-II proteins were observed with ECSCs using the
      3D culture. Y-27632 significantly inhibited the collagen gel contractility of
      ECSCs without cytotoxicity. CONCLUSIONS: The present findings suggest that the
      enhanced collagen contractility in ECSCs is associated with myofibroblastic
      differentiation, the increased expression of fibronectin and the activation of
      the Rho-ROCK-mediated signalling pathway, all of which may be involved in the
      pathogenesis of endometriosis-associated fibrosis. These results suggest that the
      inhibition of the Rho-ROCK-mediated signalling pathway may provide a novel
      strategy for the treatment of this disease. In addition, our experimental system
      of ECSCs using 3D collagen gel culture would be suitable for evaluating novel
      treatments for endometriosis.

PMID- 17204526
TI  - Can we achieve international agreement on terminologies and definitions used to
      describe abnormalities of menstrual bleeding?
AB  - BACKGROUND: There is considerable worldwide confusion in the use of terminologies
      and definitions around the symptom of abnormal uterine bleeding (AUB), and these
      are leading increasingly to difficulties in setting up multinational clinical
      trials and in interpreting the results of studies undertaken in single centres.
      An international initiative was established to develop an agreement process to
      recommend clear, simple terminologies and definitions with the potential for wide
      acceptance. METHODS: After widespread consultation with relevant international
      and national organizations, journal editors and individuals, a modified Delphi
      process was developed to assess the current use of terminologies followed by a
      structured face-to-face meeting of 35 clinicians (mostly gynaecologists) and
      scientists in Washington. Focused small group discussions led to plenary
      assessment of concepts and recommendations using an electronic keypad voting
      system. RESULTS: There was almost universal agreement that poorly defined terms
      of classical origin used in differing ways in the English medical language should
      be discarded and that these should be replaced by simple, descriptive terms with
      clear definitions which have the potential to be understood by health
      professional and patient alike and which can be translated into most languages.
      The major recommendations were to replace terms such as menorrhagia,
      metrorrhagia, hypermenorrhoea and dysfunctional uterine bleeding. Suggestions for
      potentially suitable replacement terms and definitions are made. CONCLUSIONS: A
      simple terminology has been recommended for the description and definition of
      symptoms and signs of AUB. This manuscript should be a living document and should
      be part of an ongoing process with international medical and community debate.
      Classification of causes, investigations and cultural and quality of life issues
      should be part of the ongoing process.

PMID- 17204527
TI  - A frequent Y chromosome b2/b3 subdeletion shows strong association with male
      infertility in Han-Chinese population.
AB  - BACKGROUND: Azoospermia factor c (AZFc) subdeletions were reported to be
      significant risk factors for spermatogenesis. In this study, we assessed the
      occurrence of classical AZF deletions and AZFc subdeletions and their impact on
      male infertility in a Han-Chinese population. METHODS: This study analysed a
      population of 699 subjects, including 451 idiopathic infertile patients with a
      range of fertility disorders and 248 fertile controls, using a retrospective
      design. Deletions were identified by multiplex PCR. RESULTS: The prevalence and
      phenotypes of the classical AZF deletions were similar to previous studies.
      Subdeletions of the AZFc region in patients showed similar overall frequencies in
      all sperm concentration categories of gr/gr (7.0%) and b2/b3 (8.9%). For
      controls, these subdeletions were also found with a prevalence of gr/gr (7.7%)
      and b2/b3 (3.2%). b1/b3 deletions were not found either in the patients or in the
      controls. CONCLUSION: Our data showed a higher frequency of deletion events in
      this Han-Chinese population than in populations elsewhere in the world. The
      classical AZF deletions were the primary genetic factors for spermatogenic
      failure, while no significant association was found for AZFc subdeletions with
      sperm concentration. However, the b2/b3 subdeletion was significantly associated
      with idiopathic male infertility (odds ratio, 2.93; 95% confidence interval 1.34
      6.39) (P = 0.005), indicating a potential impairment of male fertility.

PMID- 17204528
TI  - A comparative study of the effect of continuous combined conjugated equine
      estrogen plus medroxyprogesterone acetate and tibolone on blood coagulability.
AB  - BACKGROUND: Hormone therapy (HT) after the menopause is associated with increased
      risk of venous thromboembolism (VTE). Tibolone has pharmacodynamic properties
      different from other hormone preparations. We compared the effect of a combined
      HT and tibolone on the inhibition of haemostasis. METHODS: Thirty-eight post
      menopausal women were randomly assigned to 1.25 or 2.5 mg per day of tibolone or
      oral continuous combined conjugated equine estrogen plus medroxyprogesterone
      acetate (CEE/MPA). Inhibitors of haemostasis were measured at baseline and after
      12 months. RESULTS: Results from the two groups of women receiving tibolone were
      not significantly different and, to improve the power of the study, the two
      groups were merged. Higher concentration of protein S (1.16 versus 1.00 IU ml(
      1); P = 0.005) and higher activated protein C resistance ratio (APC-R) (4.2
      versus 3.65; P = 0.04) were observed in the tibolone group than in the CEE/MPA
      group. Both doses of tibolone increased APC-R significantly (P < 0.01). Tissue
      factor pathway inhibitor (TFPI) was lower in the CEE/MPA group than in the
      tibolone group (67.8 versus 79.9 ng ml(-1); P = 0.03). CEE/MPA reduced the
      concentration of antithrombin (P = 0.002), protein S (P < 0.001) and TFPI (P <
      0.001). Both preparations reduced the concentration of plasminogen activator
      inhibitor 1 (P < 0.05). CONCLUSIONS: Tibolone induces fewer pharmacological
      alterations on blood coagulability than CEE/MPA and has a potentially favourable
      effect on APC-R. This may translate into a corresponding low risk of VTE, as also
      indicated from the existing clinical data.

PMID- 17204529
TI  - Infertility, infertility treatment and twinning: the Danish National Birth
      Cohort.
AB  - BACKGROUND: We have previously observed that an increasing time to pregnancy
      (TTP) is associated with a reduced frequency of twin deliveries in couples not
      receiving infertility treatment. By using updated information, we assessed the
      frequencies of dizygotic (DZ) and monozygotic (MZ) twin deliveries as a function
      of infertility (TTP > 12 months), as well as infertility treatment. METHODS: From
      the Danish National Birth Cohort (1997-2003), we identified 51 730 fertile
      couples with TTP <or= 12 months, 5838 infertile couples who conceived naturally
      with TTP > 12 months and 5163 infertile couples who conceived after treatment.
      Information on zygosity, available for part of the cohort (1997-2000), was based
      on standardized questions on the similarities between the twins at the age of 3-5
      years. RESULTS: Compared with fertile couples, the frequency of DZ twin
      deliveries was lower for infertile couples conceiving naturally (odds ratio 0.4,
      95% confidence interval 0.2-0.7) and was much higher for infertile couples
      conceiving after treatment (17.3, 14.4-20.7). The frequency of DZ twin deliveries
      decreased with TTP in untreated couples, whereas the frequency of MZ twin
      deliveries remained constant. CONCLUSIONS: The frequency of DZ twin deliveries
      decreased with TTP and substantially increased with infertility treatment,
      whereas MZ twin deliveries remained substantially unchanged.

PMID- 17204530
TI  - The human sex ratio in New York City did not change after 11 September 2001.

PMID- 17204531
TI  - Single embryo transfer in preimplantation genetic diagnosis cycles for women <36
      years does not reduce delivery rate.
AB  - BACKGROUND: The Belgian legislation imposes single embryo transfer (SET) on women
      of <36 years in their first treatment cycle to avoid multiple pregnancies. The
      aim of this study is to assess the impact of this legislation on the outcome of
      preimplantation genetic diagnosis (PGD) for inherited diseases in young women
      undergoing SET. METHODS: A retrospective analysis of PGD cycles for monogenic
      disorders and translocations in women <36 years on their first treatment cycle.
      Two groups of patients were defined according to the implementation of the
      Belgian legislation: (i) double embryo transfer (DET), January 2001-June 2003
      (ii) SET, July 2003-June 2005. The primary and secondary outcome measures were
      delivery per embryo transfer and multiple pregnancy rates, respectively. A
      subgroup analysis for monogenic disorders and translocations was performed.
      RESULTS: 62 cycles were included in the DET group and 73 cycles in the SET group.
      The mean age, number of cumulus-oocyte complexes, number of fertilized oocytes,
      number of biopsied and cryopreserved embryos were comparable between both groups.
      There was no significant difference in the delivery rates between the DET and the
      SET groups (33.9% versus 27.4%, respectively). Multiple pregnancies were avoided
      when SET was performed. When monogenic disorders and chromosomal translocations
      were separately evaluated, no significant difference in the delivery rate after
      SET was observed. CONCLUSIONS: The implementation of a SET policy in young women
      undergoing PGD for monogenic disorders and translocations enables a significant
      reduction of multiple pregnancies without significantly affecting the delivery
      rate.

PMID- 17204532
TI  - Psychiatric symptoms and quality of life in schizophrenia: a meta-analysis.
AB  - Quality of life (QoL) has been recognized as an important outcome of
      schizophrenia treatment, yet the determinants of QoL for individuals with
      schizophrenia are not well known. Research has consistently found psychiatric
      symptoms to be negatively related to QoL, however, findings concerning the
      strength of these relationships have been mixed, making it difficult to determine
      the degree to which such symptoms are related to poor QoL. This research presents
      a systematic meta-analysis of studies examining the relationship between
      psychiatric symptoms and QoL in schizophrenia, in an effort to elucidate the
      determinants of QoL for this population. A total of 56 studies were extracted
      from literature searches of relevant databases for empirical reports published
      between 1966 and 2005 examining the relationship between positive, negative,
      and/or general psychiatric symptoms and QoL. Weighted effect size analyses
      revealed small relationships between psychiatric symptoms and QoL, with general
      psychopathology showing the strongest negative associations across all QoL
      indicators. Moderator analyses indicated that variation in effect sizes could be
      accounted for by differing operationalizations of QoL, study design, sample, and
      participant treatment setting. In particular, positive and negative symptoms were
      more strongly related to poor QoL among studies of schizophrenia outpatients,
      whereas general psychopathology showed a consistent negative relationship with
      QoL across all study samples and treatment settings. Implications for future
      research and treatment development are discussed.

PMID- 17204533
TI  - Quantitative analysis of the phenotypic variability of shoot architecture in two
      grapevine (Vitis vinifera) cultivars.
AB  - BACKGROUND AND AIMS: Plant architecture and its interaction with agronomic
      practices and environmental constraints are determinants of the structure of the
      canopy, which is involved in carbon acquisition and fruit quality development. A
      framework for the quantitative analysis of grapevine (Vitis vinifera) shoot
      architecture, based on a set of topological and geometrical parameters, was
      developed for the identification of differences between cultivars and the origins
      of phenotypic variability. METHODS: Two commercial cultivars ('Grenache N',
      'Syrah') with different shoot architectures were grown in pots, in well-irrigated
      conditions. Shoot topology was analysed, using a hidden semi-Markov chain and
      variable-order Markov chains to identify deviations from the normal pattern of
      succession of phytomer types (P0-P1-P2), together with kinematic analysis of
      shoot axis development. Shoot geometry was characterized by final internode and
      individual leaf area measurements. KEY RESULTS: Shoot architecture differed
      significantly between cultivars. Secondary leaf area and axis length were greater
      for 'Syrah'. Secondary leaf area distribution along the main axis also differed
      between cultivars, with secondary leaves preferentially located towards the basal
      part of the shoot in 'Syrah'. The main factors leading to differences in leaf
      area between the cultivars were: (a) slight differences in main shoot structure,
      with the supplementary P0 phytomer on the lower part of the shoot in 'Grenache
      N', which bears a short branch; and (b) an higher rate and duration of
      development of branches bearing by P1-P2 phytomers related to P0 ones at the
      bottom of the shoot in 'Syrah'. Differences in axis length were accounted for
      principally by differences in individual internode morphology, with 'Syrah'
      having significantly longer internodes. This trait, together with a smaller shoot
      diameter, may account for the characteristic 'droopy' habit of 'Syrah' shoots.
      CONCLUSIONS: This study highlights the architectural parameters involved in the
      phenotypic variability of shoot architecture in two grapevine cultivars.
      Differences in primary shoot structure and in branch development potential
      accounted for the main differences in leaf area distribution between the two
      cultivars. By contrast, shoot shape seemed to be controlled by differences in
      axis length due principally to differences in internode length.

PMID- 17204534
TI  - Genome size evolution in relation to leaf strategy and metabolic rates revisited.
AB  - BACKGROUND AND AIMS: It has been proposed that having too much DNA may carry
      physiological consequences for plants. The strong correlation between DNA
      content, cell size and cell division rate could lead to predictable morphological
      variation in plants, including a negative relationship with leaf mass per unit
      area (LMA). In addition, the possible increased demand for resources in species
      with high DNA content may have downstream effects on maximal metabolic
      efficiency, including decreased metabolic rates. METHODS: Tests were made for
      genome size-dependent variation in LMA and metabolic rates (mass-based
      photosynthetic rate and dark respiration rate) using our own measurements and
      data from a plant functional trait database (Glopnet). These associations were
      tested using two metrics of genome size: bulk DNA amount (2C DNA) and monoploid
      genome size (1Cx DNA). The data were analysed using an evolutionary framework
      that included a regression analysis and independent contrasts using a
      phylogenetic tree with estimates of molecular diversification times. A
      contribution index for the LMA data set was also calculated to determine which
      divergences have the greatest influence on the relationship between genome size
      and LMA. KEY RESULTS AND CONCLUSIONS: A significant negative association was
      found between bulk DNA amount and LMA in angiosperms. This was primarily a result
      of influential divergences that may represent early shifts in growth form.
      However, divergences in bulk DNA amount were positively associated with
      divergences in LMA, suggesting that the relationship may be indirect and mediated
      through other traits directly related to genome size. There was a significant
      negative association between genome size and metabolic rates that was driven by a
      basal divergence between angiosperms and gymnosperms; no significant independent
      contrast results were found. Therefore, it is concluded that genome size
      dependent constraints acting on metabolic efficiency may not exist within seed
      plants.

PMID- 17204535
TI  - Daytime depression in tree stem CO2 efflux rates: is it caused by low stem turgor
      pressure?
AB  - BACKGROUND AND AIMS: Daytime CO2 efflux rates (FCO2) from tree stems are often
      reported to be lower than expected from the exponential relationship between
      temperature and respiration. Explanations of daytime depression in FCO2 have
      focused on the possible role of internal CO2 transport in the xylem. However,
      another possible cause that has been overlooked is the daily dynamics of the
      water status in the living stem tissues and its influence on stem growth rate and
      thus respiration. The objective of this study was to assess the daily dynamics of
      stem water status and growth rate and to determine the extent to which they may
      be linked to daily variations in stem FCO2. METHODS: FCO2 of young beech and oak
      stems were measured under controlled conditions. Relative stem turgor pressure
      (Psi(p)), obtained from simulations with the 'RCGro' model, was used as an
      indicator of the water status in the living stem tissues. Daily dynamics of stem
      growth were derived from Psi(p): growth was assumed to occur when Psi(p) exceeded
      a relative threshold value. KEY RESULTS: There was a strong correspondence
      between fluctuations in FCO2 and simulated Psi(p). The non-growth conditions
      during daytime coincided with depressions in FCO2. Moreover, FCO2 responded to
      changes in Psi(p) in the absence of growth, indicating also that maintenance
      processes were influenced by the water status in the living stem tissues.
      CONCLUSIONS: Daytime depressions in stem FCO2 correlate with the daily dynamics
      of turgor, as a measure of the water status in the living stem tissues: it is
      suggested that water status of tree stems is a potentially important determinant
      of stem FCO2, as it influences the rate of growth and maintenance processes in
      the living tissues of the stem.

PMID- 17204536
TI  - Corolla herbivory, pollination success and fruit predation in complex flowers: an
      experimental study with Linaria lilacina (Scrophulariaceae).
AB  - BACKGROUND AND AIMS: Herbivory on floral structures has been postulated to
      influence the evolution of floral traits in some plant species, and may also be
      an important factor influencing the occurrence and outcome of subsequent biotic
      interactions related to floral display. In particular, corolla herbivory may
      affect structures differentially involved in flower selection by pollinators and
      fruit predators (specifically, those ovopositing in ovaries prior to fruit
      development); hence floral herbivores may influence the relationships between
      these mutualistic and antagonistic agents. METHODS: The effects of corolla
      herbivory in Linaria lilacina (Scrophulariaceae), a plant species with complex
      flowers, were considered in relation to plant interactions with pollinators and
      fruit predators. Tests were made as to whether experimentally created differences
      in flower structure (resembling those occurring naturally) may translate into
      differences in reproductive output in terms of fruit or seed production. KEY
      RESULTS: Flowers with modified corollas, particularly those with lower lips
      removed, were less likely to be selected by pollinators than control flowers, and
      were less likely to be successfully visited and pollinated. As a consequence,
      fruit production was also less likely in these modified flowers. However, none of
      the experimental treatments affected the likelihood of visitation by fruit
      predators. CONCLUSIONS: Since floral herbivory may affect pollinator visitation
      rates and reduce seed production, differences among plants in the proportion of
      flowers affected by herbivory and in the intensity of the damage inflicted on
      affected flowers may result in different opportunities for reproduction for
      plants in different seasons.

PMID- 17204537
TI  - Plants living on gypsum: beyond the specialist model.
AB  - BACKGROUND AND AIMS: Plants from gypsum habitats are classified as gypsophiles
      and gypsovags. The former include both narrow endemics limited to small gypsum
      areas and regionally dominant gypsophiles growing in gypsum areas of large
      regions, whereas gypsovags are plants that can grow both in gypsum and non-gypsum
      soils. Factors controlling the distribution of gypsum plants are still not fully
      understood. METHODS: To assess how the different types of gypsum plants deal with
      the stressful conditions of gypsum substrates, comparisons were made of the leaf
      chemical composition of four gypsovags, five regionally dominant gypsophiles and
      four narrow gypsum endemics growing in two massive gypsum areas of the Iberian
      Peninsula. KEY RESULTS: The chemical composition of gypsovags was clearly
      different from regionally dominant gypsophiles, while the chemical composition of
      narrow-gypsophile endemics was more similar to the chemical composition of
      gypsovags than to that of regionally dominant gypsophiles. Regionally dominant
      gypsophiles showed higher concentrations of ash, Ca, S, N, Mg P and Na, whereas
      gypsovags and local gypsophile endemics displayed higher concentrations of C and
      greater C : N ratios. CONCLUSIONS: Such differences suggest that the three groups
      of gypsum plants follow diverse ecological strategies. It is suggested that
      regionally dominant gypsophiles might fit the 'specialist' model, being species
      specifically adapted to gypsum, whereas both gypsovags and narrow-gypsophile
      endemics might fit the 'refuge' model, being stress-tolerant species that find
      refuge on gypsum soils from competition. The analysis of the leaf chemical
      composition could be a good predictor of the degree of plants specialization to
      gypsum soils.

PMID- 17204538
TI  - Mutual regulation of Arabidopsis thaliana ethylene-responsive element binding
      protein and a plant floral homeotic gene, APETALA2.
AB  - BACKGROUND AND AIMS: It has previously been shown that Arabidopsis thaliana
      ethylene-responsive element binding protein (AtEBP) contributed to resistance to
      abiotic stresses. Interestingly, it has also been reported that expression of
      ethylene-responsive factor (ERF) genes including AtEBP were regulated by the
      activity of APETALA2 (AP2), a floral homeotic factor. AP2 is known to regulate
      expression of several floral-specific homeotic genes such as AGAMOUS. The aim of
      this study was to clarify the relationship between AP2 and AtEBP in gene
      expression. METHODS: Northern blot analysis was performed on ap2 mutants,
      ethylene-related Arabidopsis mutants and transgenic Arabidopsis plants over
      expressing AtEBP, and a T-DNA insertional mutant of AtEBP. Phenotypic analysis of
      these plants was performed. KEY RESULTS: Expression levels of ERF genes such as
      AtEBP and AtERF1 were increased in ap2 mutants. Over-expression of AtEBP caused
      upregulation of AP2 expression in leaves. AP2 expression was suppressed by the
      null-function of ethylene-insensitive2 (EIN2), although AP2 expression was not
      affected by ethylene treatment. Loss of AtEBP function slightly reduced the
      average number of stamens. CONCLUSIONS: AP2 and AtEBP are mutually regulated in
      terms of gene expression. AP2 expression was affected by EIN2 but was not
      regulated by ethylene treatment.

PMID- 17204539
TI  - Ammonium and nitrate uptake by the floating plant Landoltia punctata.
AB  - BACKGROUND AND AIMS: Plants from the family Lemnaceae are widely used in
      ecological engineering projects to purify wastewater and eutrophic water bodies.
      However, the biology of nutrient uptake mechanisms in plants of this family is
      still poorly understood. There is controversy over whether Lemnaceae roots are
      involved in nutrient uptake. No information is available on nitrogen (N)
      preferences and capacity of Landoltia punctata (dotted duckweed), one of the best
      prospective species in Lemnaceae for phytomelioration and biomass production. The
      aim of this study was to assess L. punctata plants for their ability to take up
      NH4+ and NO3- by both roots and fronds. METHODS: NO3- and NH4+ fluxes were
      estimated by a non-invasive ion-selective microelectrode technique. This
      technique allows direct measurements of ion fluxes across the root or frond
      surface of an intact plant. KEY RESULTS: Landoltia punctata plants took up NH4+
      and NO3- by both fronds and roots. Spatial distribution of NH4+ and NO3- fluxes
      demonstrated that, although ion fluxes at the most distal parts of the root were
      uneven, the mature part of the root was involved in N uptake. Despite the
      absolute flux values for NH4+ and NO3- being lower in roots than at the frond
      surface, the overall capacity of roots to take up ions was similar to that of
      fronds because the surface area of roots was larger. L. punctata plants preferred
      to take up NH4+ over NO3- when both N sources were available. CONCLUSIONS:
      Landoltia punctata plants take up nitrogen by both roots and fronds. When both
      sources of N are available, plants prefer to take up NH4+, but will take up NO3-
      when it is the only N source.

PMID- 17204540
TI  - Effect of nitrogen form and root-zone pH on growth and nitrogen uptake of tea
      (Camellia sinensis) plants.
AB  - BACKGROUND AND AIMS: Tea (Camellia sinensis) is considered to be acid tolerant
      and prefers ammonium nutrition, but the interaction between root zone acidity and
      N form is not properly understood. The present study was performed to
      characterize their interaction with respect to growth and mineral nutrition.
      METHODS: Tea plants were hydroponically cultured with NH4+, NO3- and NH(4+) + NO3
      , at pH 4.0, 5.0 and 6.0, which were maintained by pH stat systems. KEY RESULTS:
      Plants supplied with NO3- showed yellowish leaves resembling nitrogen deficiency
      and grew much slower than those receiving NH4+ or NH(4+) + NO3- irrespective of
      root-zone pH. Absorption of NH4+ was 2- to 3.4-fold faster than NO3- when
      supplied separately, and 6- to 16-fold faster when supplied simultaneously.
      Nitrate-grown plants had significantly reduced glutamine synthetase activity, and
      lower concentrations of total N, free amino acids and glucose in the roots, but
      higher concentrations of cations and carboxylates (mainly oxalate) than those
      grown with NH4+ or NH(4+) + NO3-. Biomass production was largest at pH 5.0
      regardless of N form, and was drastically reduced by a combination of high root
      zone pH and NO3-. Low root-zone pH reduced root growth only in NO(3-)-fed plants.
      Absorption of N followed a similar pattern as root-zone pH changed, showing
      highest uptake rates at pH 5.0. The concentrations of total N, free amino acids,
      sugars and the activity of GS were generally not influenced by pH, whereas the
      concentrations of cations and carboxylates were generally increased with
      increasing root-zone pH. CONCLUSIONS: Tea plants are well-adapted to NH(4+)-rich
      environments by exhibiting a high capacity for NH4+ assimilation in their roots,
      reflected in strongly increased key enzyme activities and improved carbohydrate
      status. The poor plant growth with NO3- was largely associated with inefficient
      absorption of this N source. Decreased growth caused by inappropriate external pH
      corresponded well with the declining absorption of nitrogen.

PMID- 17204541
TI  - A model explaining genotypic and ontogenetic variation of leaf photosynthetic
      rate in rice (Oryza sativa) based on leaf nitrogen content and stomatal
      conductance.
AB  - BACKGROUNDS AND AIMS: Identification of physiological traits associated with leaf
      photosynthetic rate (Pn) is important for improving potential productivity of
      rice (Oryza sativa). The objectives of this study were to develop a model which
      can explain genotypic variation and ontogenetic change of Pn in rice under
      optimal conditions as a function of leaf nitrogen content per unit area (N) and
      stomatal conductance (g(s)), and to quantify the effects of interaction between N
      and g(s) on the variation of Pn. METHODS: Pn, N and g(s) were measured at
      different developmental stages for the topmost fully expanded leaves in ten rice
      genotypes with diverse backgrounds grown in pots (2002) and in the field (2001
      and 2002). A model of Pn that accounts for carboxylation and CO diffusion
      processes, and assumes that the ratio of internal conductance to g(s) is
      constant, was constructed, and its goodness of fit was examined. KEY RESULTS:
      Considerable genotypic differences in Pn were evident for rice throughout
      development in both the pot and field experiments. The genotypic variation of Pn
      was correlated with that of g(s) at a given stage, and the change of Pn with
      plant development was closely related to the change of N. The variation of g(s)
      among genotypes was independent of that of N. The model explained well the
      variation in Pn of the ten genotypes grown under different conditions at
      different developmental stages. Conclusions The response of Pn to increased N
      differs with g(s), and the increase in Pn of genotypes with low g(s) is smaller
      than that of genotypes with high g(s). Therefore, simultaneous improvements of
      these two traits are essential for an effective breeding of rice genotypes with
      increased Pn.

PMID- 17204542
TI  - Concurrent duodenal manometric and impedance recording to evaluate the effects of
      hyoscine on motility and flow events, glucose absorption, and incretin release.
AB  - Upper gastrointestinal motor function and incretin hormone secretion are major
      determinants of postprandial glycemia and insulinemia. However, the impact of
      small intestinal flow events on glucose absorption and incretin release is poorly
      defined. Intraluminal impedance monitoring is a novel technique that allows flow
      events to be quantified. Eight healthy volunteers were studied twice, in random
      order. A catheter incorporating six pairs of electrodes at 3-cm intervals, and
      six corresponding manometry sideholes, was positioned in the duodenum. Hyoscine
      butylbromide (20 mg) or saline was given as an intravenous bolus, followed by a
      continuous intravenous infusion of either hyoscine (20 mg/h) or saline over 60
      min. Concurrently, glucose and 3-O-methylglucose (3-OMG) were infused into the
      proximal duodenum (3 kcal/min), with frequent blood sampling to measure glucose,
      3-OMG, insulin, glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP). The frequency of duodenal pressure waves and
      propagated pressure wave sequences was reduced by hyoscine in the first 10 min
      (P<0.01 for both), but not after that time. In contrast, there were markedly
      fewer duodenal flow events throughout 60 min with hyoscine (P<0.005). Overall,
      blood glucose (P<0.01) and plasma 3-OMG concentrations (P<0.05) were lower during
      hyoscine than saline, whereas plasma insulin, GLP-1, and GIP concentrations were
      initially (t=20 min) lower during hyoscine (P<0.05). In conclusion, intraluminal
      impedance measurement may be more sensitive than manometry in demonstrating
      alterations in duodenal motor function. A reduction in the frequency of duodenal
      flow events is associated with a decreased rate of glucose absorption and
      incretin release in healthy subjects.

PMID- 17204543
TI  - Iron chelation acutely stimulates fetal human intestinal cell production of IL-6
      and VEGF while decreasing HGF: the roles of p38, ERK, and JNK MAPK signaling.
AB  - Bacteria have developed mechanisms to sequester host iron via chelators such as
      deferoxamine (DFO). Interestingly, DFO has been shown to stimulate acute
      intestinal epithelial cell inflammatory cytokine production in the absence of
      bacteria; however, this mechanism has not been elucidated. Intestinal epithelial
      cell production of IL-6 and TNF-alpha is elevated in various gastrointestinal
      pathologies, including acute intestinal ischemia. Similarly, VEGF and HGF are
      essential to intestinal epithelial cell integrity. Therapeutic strategies that
      decrease IL-6 and TNF-alpha while increasing VEGF and HGF therefore have
      theoretical appeal. We hypothesized that 1) fetal human intestinal epithelial
      cells acutely produce increased IL-6, TNF-alpha, VEGF, and HGF during iron
      chelation and 2) the MAPK pathway mediates these effects. Fetal human intestinal
      epithelial cells were stimulated by iron chelation (1 mM DFO) with and without
      p38 MAPK, ERK, or JNK inhibition. Supernatants were harvested after 24 h of
      incubation, and IL-6, TNF-alpha, VEGF, and HGF levels were quantified by ELISA.
      Activation of MAPK pathways was confirmed by Western blot analysis. DFO
      stimulation resulted in a significant increase in epithelial cell IL-6 and VEGF
      production while yielding a decrease in HGF production (P<0.05). Unexpectedly,
      TNF-alpha was not detectable. p38 MAPK, ERK, and JNK inhibition significantly
      decreased IL-6, VEGF, and HGF production (P<0.05). In conclusion, DFO acutely
      increases fetal human intestinal epithelial cell IL-6 and VEGF expression while
      causing an unexpected decrease in HGF expression and no detectable TNF-alpha
      production. Furthermore, chelator-induced intestinal epithelial cell cytokine
      expression depends on p38, ERK, and JNK MAPK pathways.

PMID- 17204545
TI  - IL-1beta modulation of H,K-ATPase alpha-subunit gene transcription in
      Helicobacter pylori infection.
AB  - Helicobacter pylori infection of the human gastric body induces hypochlorhydria
      by perturbing acid secretion. H. pylori inhibits parietal cell H,K-ATPase alpha
      subunit (HKalpha) gene and protein expression, providing a mechanistic basis for
      clinical hypochlorhydria. Given that H. pylori infection increases gastric
      mucosal IL-1beta, an acid secretory inhibitor, we investigated the role of IL
      1beta in H. pylori-mediated inhibition of HKalpha transcription. Human gastric
      adenocarcinoma (AGS) cells were transfected with promoter-reporter constructs
      containing human HKalpha 5'-flanking sequence deletions. IL-1beta (10 ng/ml) had
      no effect on the transcriptional activity of six progressively shorter deletion
      constructs of the HKalpha promoter (HKalpha2179-HKalpha340) and significantly
      stimulated the activity of HKalpha206, HKalpha177, HKalpha165, and HKalpha102
      deletion constructs (80%, 100%, 46%, and 35%, respectively). H. pylori inhibited
      the transcriptional activity of HKalpha2179, HKalpha206, HKalpha177, and
      HKalpha165; IL-1beta relieved the H. pylori inhibition of HKalpha2179 and
      HKalpha206 activity but not HKalpha177 and HKalpha165 activity. AGS cell
      pretreatment with a MEK1/2 inhibitor prevented the IL-1beta-mediated stimulation,
      but p38 and JNK pathway inhibitors did not. IL-1beta mRNA levels in AGS cells
      were low and unaffected by H. pylori, and ELISAs of H. pylori-conditioned AGS
      culture media showed no measurable IL-1beta secretion. These data indicate that
      an IL-1beta-dependent cis-response element lies downstream of -206 nt in the
      HKalpha promoter and that IL-1beta-mediated upregulation of HKalpha transcription
      is affected by an ERK1/2 kinase signal pathway. We conclude that an IL-1beta
      responsive HKalpha cis element positively regulates HKalpha gene transcription in
      shortened deletion constructs and that H. pylori-induced inhibition of HKalpha
      transcription is not mediated by IL-1beta.

PMID- 17204544
TI  - Molecular basis for calcium signaling in hepatic stellate cells.
AB  - Progressive liver fibrosis (with the resultant cirrhosis) is the primary cause of
      chronic liver failure. Hepatic stellate cells (HSCs) are critically important
      mediators of liver fibrosis. In the healthy liver, HSCs are quiescent lipid
      storing cells limited to the perisinusoidal endothelium. However, in the injured
      liver, HSCs undergo myofibroblastic transdifferentiation (activation), which is a
      critical step in the development of organ fibrosis. HSCs express P2Y receptors
      linking extracellular ATP to inositol (1,4,5)-trisphosphate-mediated cytosolic
      Ca(2+) signals. Here, we report that HSCs express only the type I inositol
      (1,4,5)-trisphosphate receptor and that the receptor shifts into the nucleus and
      cell extensions upon activation. These cell extensions, furthermore, express
      sufficient machinery to enable local application of ATP to evoke highly localized
      Ca(2+) signals that induce localized contractions. These autonomous units of
      subcellular signaling and response reveal a new level of subcellular
      organization, which, in turn, establishes a novel paradigm for the local control
      of fibrogenesis in the liver.

PMID- 17204546
TI  - Vagal modulation of intestinal afferent sensitivity to systemic LPS in the rat.
AB  - The central nervous system modulates inflammation in the gastrointestinal tract
      via efferent vagal pathways. We hypothesized that these vagal efferents receive
      synaptic input from vagal afferents, representing an autonomic feedback
      mechanism. The consequence of this vagovagal reflex for afferent signal
      generation in response to LPS was examined in the present study. Different
      modifications of the vagal innervation or sham procedures were performed in
      anesthetized rats. Extracellular mesenteric afferent nerve discharge and systemic
      blood pressure were recorded in vivo before and after systemic administration of
      LPS (6 mg/kg iv). Mesenteric afferent nerve discharge increased dramatically
      following LPS, which was unchanged when vagal efferent traffic was eliminated by
      acute vagotomy. In chronically vagotomized animals, to eliminate both vagal
      afferent and efferent traffic, the increase in afferent firing 3.5 min after LPS
      was reduced to 3.2 +/- 2.5 impulses/s above baseline compared with 42.2 +/- 2.0
      impulses/s in controls (P < 0.001). A similar effect was observed following
      perivagal capsaicin, which was used to eliminate vagal afferent traffic only. LPS
      also caused a transient hypotension (<10 min), a partial recovery, and then
      persistent hypertension that was exacerbated by all three procedures.
      Mechanosensitivity was increased 15 min following LPS but had recovered at 30 min
      in all subgroups except for the chronic vagotomy group. In conclusion, discharge
      in capsaicin-sensitive mesenteric vagal afferents is augmented following systemic
      LPS. This activity, through a vagovagal pathway, helps to attenuate the effects
      of septic shock. The persistent hypersensitivity to mechanical stimulation after
      chronic vagal denervation suggests that the vagus exerts a regulatory influence
      on spinal afferent sensitization following LPS.

PMID- 17204547
TI  - IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in
      vitro.
AB  - The IL-10-like cytokine IL-22 is produced by activated T cells. In this study, we
      analyzed the role of this cytokine system in hepatic cells. Expression studies
      were performed by RT-PCR and quantitative PCR. Signal transduction was analyzed
      by Western blot experiments and ELISA. Cell proliferation was measured by MTS and
      [(3)H]thymidine incorporation assays. Hepatocyte regeneration was studied in in
      vitro restitution assays. Binding of IL-22 to its receptor complex expressed on
      human hepatic cells and primary human hepatocytes resulted in the activation of
      MAPKs, Akt, and STAT proteins. IL-22 stimulated cell proliferation and migration,
      which were both significantly inhibited by the phosphatidylinositol 3-kinase
      inhibitor wortmannin. IL-22 increased the mRNA expression of suppressor of
      cytokine signaling (SOCS)-3 and the proinflammatory cytokines IL-6, IL-8, and TNF
      alpha. SOCS-1/3 overexpression abrogated IL-22-induced STAT activation and
      decreased IL-22-mediated liver cell regeneration. Hepatic IL-22 mRNA expression
      was detectable in different forms of human hepatitis, and hepatic IL-22 mRNA
      levels were increased in murine T cell-mediated hepatitis in vivo following
      cytomegalovirus infection, whereas no significant differences were seen in an in
      vivo model of ischemia-reperfusion injury. In conclusion, IL-22 promotes liver
      cell regeneration by increasing hepatic cell proliferation and hepatocyte
      migration through the activation of Akt and STAT signaling, which is abrogated by
      SOCS-1/3 overexpression.

PMID- 17204548
TI  - Gene expression and protein length influence codon usage and rates of sequence
      evolution in Populus tremula.
AB  - Codon bias is generally thought to be determined by a balance between mutation,
      genetic drift, and natural selection on translational efficiency. However,
      natural selection on codon usage is considered to be a weak evolutionary force
      and selection on codon usage is expected to be strongest in species with large
      effective population sizes. In this paper, I study associations between codon
      usage, gene expression, and molecular evolution at synonymous and nonsynonymous
      sites in the long-lived, woody perennial plant Populus tremula (Salicaceae).
      Using expression data for 558 genes derived from expressed sequence tags (EST)
      libraries from 19 different tissues and developmental stages, I study how gene
      expression levels within single tissues as well as across tissues affect codon
      usage and rates sequence evolution at synonymous and nonsynonymous sites. I show
      that gene expression have direct effects on both codon usage and the level of
      selective constraint of proteins in P. tremula, although in different ways. Codon
      usage genes is primarily determined by how highly expressed a genes is, whereas
      rates of sequence evolution are primarily determined by how widely expressed
      genes are. In addition to the effects of gene expression, protein length appear
      to be an important factor influencing virtually all aspects of molecular
      evolution in P. tremula.

PMID- 17204549
TI  - Sexual differentiation of Kiss1 gene expression in the brain of the rat.
AB  - The Kiss1 gene codes for kisspeptins, which have been implicated in the
      neuroendocrine regulation of reproduction. In the brain, Kiss1 mRNA-expressing
      neurons are located in the arcuate (ARC) and anteroventral periventricular (AVPV)
      nuclei. Kiss1 neurons in the AVPV appear to play a role in generating the
      preovulatory GnRH/LH surge, which occurs only in females and is organized
      perinatally by gonadal steroids. Because Kiss1 is involved in the sexually
      dimorphic GnRH/LH surge, we hypothesized that Kiss1 expression is sexually
      differentiated, with females having more Kiss1 neurons than either males or
      neonatally androgenized females. To test this, male and female rats were
      neonatally treated with androgen or vehicle; then, as adults, they were left
      intact or gonadectomized and implanted with capsules containing sex steroids or
      nothing. Kiss1 mRNA levels in the AVPV and ARC were determined by in situ
      hybridization. Normal females expressed significantly more Kiss1 mRNA in the AVPV
      than normal males, even under identical adult hormonal conditions. This Kiss1 sex
      difference was organized perinatally, as demonstrated by the observation that
      neonatally androgenized females displayed a male-like pattern of adulthood Kiss1
      expression in the AVPV. In contrast, there was neither a sex difference nor an
      influence of neonatal treatment on Kiss1 expression in the ARC. Using double
      labeling techniques, we determined that the sexually differentiated Kiss1 neurons
      in the AVPV are distinct from the sexually differentiated population of tyrosine
      hydroxylase (dopaminergic) neurons in this region. Our findings suggest that sex
      differences in kisspeptin signaling from the AVPV subserve the cellular
      mechanisms controlling the sexually differentiated GnRH/LH surge.

PMID- 17204550
TI  - Relaxin antagonizes hypertrophy and apoptosis in neonatal rat cardiomyocytes.
AB  - The pregnancy hormone relaxin has recently been shown to be cardio-protective.
      Despite its well-established antifibrotic actions in the heart, the effects of
      relaxin on cardiomyocytes (CM) remain to be determined. We investigated effects
      of isoform 2 of the human relaxin (H2-relaxin) on CM hypertrophy and apoptosis.
      In cultured neonatal rat CM, phenylephrine (50 microM) and cardiac fibroblast
      conditioned medium were used respectively to induce CM hypertrophy. The degree of
      hypertrophy was indicated by increased cell size, protein synthesis and gene
      expression of atrial natriuretic peptide. Although H2-relaxin (16.7 nM) alone
      failed to suppress hypertrophy induced by phenylephrine, it repressed the cardiac
      fibroblast-conditioned medium-induced increase in protein synthesis by 24%
      (P<0.05) and reversed the increase in cell size (P<0.001) and atrial natriuretic
      peptide expression (P<0.01). We further studied the effect of H2-relaxin on CM
      apoptosis induced by H2O2 (200 microM). Studies of DNA laddering and nuclear
      staining demonstrated that H2-relaxin treatment reduced H2O2-induced DNA
      fragmentation. Real-time PCR and Western blot analysis revealed a significant
      increase in the Bcl2/Bax ratio in H2-relaxin-treated CM. Further analysis showed
      that activation of Akt (1.8-fold, P<0.001) and ERK (2.0-fold, P<0.01) were
      involved in the antiapoptotic action of H2-relaxin in CM, and that Gi/o coupling
      of relaxin receptors was associated with the H2-relaxin-induced Akt activation in
      CM. In conclusion, these results extend our current knowledge of the cardiac
      actions of relaxin by demonstrating that H2-relaxin indirectly inhibits CM
      hypertrophy and directly protects CM from apoptosis.

PMID- 17204551
TI  - Obestatin partially affects ghrelin stimulation of food intake and growth hormone
      secretion in rodents.
AB  - Administration of ghrelin, an endogenous ligand for the GH secretagogue receptor
      1a (GHSR 1a), induces potent stimulating effects on GH secretion and food intake.
      However, more than 7 yr after its discovery, the role of endogenous ghrelin
      remains elusive. Recently, a second peptide, obestatin, also generated from
      proteolytic cleavage of preproghrelin has been identified. This peptide inhibits
      food intake and gastrointestinal motility but does not modify in vitro GH release
      from pituitary cells. In this study, we have reinvestigated obestatin functions
      by measuring plasma ghrelin and obestatin levels in a period of spontaneous
      feeding in ad libitum-fed and 24-h fasted mice. Whereas fasting resulted in
      elevated ghrelin levels, obestatin levels were significantly reduced. Exogenous
      obestatin per se did not modify food intake in fasted and fed mice. However, it
      inhibited ghrelin orexigenic effect that were evident in fed mice only. The
      effects of obestatin on GH secretion were monitored in superfused pituitary
      explants and in freely moving rats. Obestatin was only effective in vivo to
      inhibit ghrelin stimulation of GH levels. Finally, the relationship between
      octanoylated ghrelin, obestatin, and GH secretions was evaluated by iterative
      blood sampling every 20 min during 6 h in freely moving adult male rats. The half
      life of exogenous obestatin (10 microg iv) in plasma was about 22 min. Plasma
      obestatin levels exhibited an ultradian pulsatility with a frequency slightly
      lower than octanoylated ghrelin and GH. Ghrelin and obestatin levels were not
      strictly correlated. In conclusion, these results show that obestatin, like
      ghrelin, is secreted in a pulsatile manner and that in some conditions; obestatin
      can modulate exogenous ghrelin action. It remains to be determined whether
      obestatin modulates endogenous ghrelin actions.

PMID- 17204552
TI  - Thyronamines are substrates for human liver sulfotransferases.
AB  - Sulfotransferases (SULTs) catalyze the sulfation of many endogenous compounds
      that include monoamine neurotransmitters, such as dopamine (DA), and thyroid
      hormones (iodothyronines). Decarboxylation of iodothyronines results in formation
      of thyronamines. In the mouse, thyronamines act rapidly in a nongenomic fashion
      to initiate hypothermia and decrease cardiac output and heart rate. These effects
      are attenuated after 1-4 h, and metabolism of thyronamines via sulfation may be a
      mechanism for termination of thyronamine action. We carried out this study to
      test thyronamine (T0AM), 3-iodothyronamine (T1AM), 3,5-diiodothyronamine (T2AM),
      and 3,5,3'-triiodothyronamine (T3AM) as substrates for human liver and cDNA
      expressed SULT activities. We characterized several biochemical properties of
      SULTs using the thyronamines that acted as substrates for SULT activities in a
      human liver high-speed supernatant pool (n=3). T1AM led to the highest SULT
      activity. Activities with T0AM and T3AM were 10-fold lower, and there was no
      detectable activity with T2AM. Thyronamines were then tested as substrates with
      eight cDNA-expressed SULTs (1A1, 1A2, 1A3, 1C2, 1E1, 2A1, 2B1a, and 2B1b).
      Expressed SULT1A3 had the greatest activity with T0AM, T1AM, and T3AM, whereas
      SULT1A1 showed similar activity only with T3AM. Expressed SULT1E1 had low
      activity with each substrate. T1AM, the most active thyronamine
      pharmacologically, was associated with the greatest SULT activity of the
      thyronamines tested in the liver pool and in both the expressed SULT1A3 and
      SULT1E1 preparations. Our results support the conclusion that sulfation
      contributes to the metabolism of thyronamines in human liver and that SULT
      activities may regulate the physiological effects of endogenous thyronamines.

PMID- 17204553
TI  - Effects of loss of classical estrogen response element signaling on bone in male
      mice.
AB  - The role of estrogen signaling in the male skeleton via estrogen receptor (ER)
      alpha is now well established. ERalpha can elicit responses through either
      classical estrogen response elements (ERE) pathways or nonclassical, non-ERE
      pathways. In the present study, we examined the effects of either the attenuation
      or loss of classical ERalpha signaling on the murine male skeleton. To accomplish
      this, we crossed male mice heterozygous for a knock-in mutation [nonclassical
      ERalpha knock-in (NERKI)], which abolishes the ERE-mediated pathway with female
      heterozygous ERalpha knockout mice (ERalpha+/-) and studied the F1 generation
      ERalpha+/+, ERalpha+/-, ERalpha+/NERKI, and ERalpha-/NERKI male progeny
      longitudinally using bone density and histomorphometry. The only ERalpha allele
      present in ERalpha-/NERKI mice is incapable of classical ERE-mediated signaling,
      whereas the heterozygous ERalpha+/NERKI mice have both one intact ERalpha and one
      NERKI allele. As compared with ERalpha+/+ littermates (n=10/genotype), male
      ERalpha+/NERKI and ERalpha-/NERKI mice displayed axial and appendicular skeletal
      osteopenia at 6, 12, 20, and 25 wk of age, as demonstrated by significant
      reductions in total bone mineral density (BMD) at representative sites (areal BMD
      by dual-energy x-ray absorptiometry at the lumbar vertebrae and femur and
      volumetric BMD by peripheral quantitative computed tomography at the tibia;
      P<0.05-0.001 vs. ERalpha+/+). The observed osteopenia in these mice was evident
      in both trabecular and cortical bone compartments. However, these decreases were
      more severe in mice lacking classical ERalpha signaling (ERalpha-/NERKI mice),
      compared with mice in which one wild-type ERalpha allele was present
      (ERalpha+/NERKI mice). Collectively, these data demonstrate that classical
      ERalpha signaling is crucial for the development of the murine male skeleton.

PMID- 17204554
TI  - Midkine is an autocrine activator of signal transducer and activator of
      transcription 3 in 3T3-L1 cells.
AB  - Mitotic clonal expansion is believed to be necessary for 3T3-L1 adipocyte
      formation. Signal transducer and activator of transcription 3 (STAT3), a
      mitogenic signaling protein, is activated through tyrosine phosphorylation during
      the proliferative phases of adipogenesis. We hypothesize that this signaling
      protein plays a key role in mitotic clonal expansion and differentiation. Here we
      determined that the adipocyte differentiation cocktail containing
      isobutylmethylxanthine, dexamethasone, and insulin (MDI) induced STAT3 tyrosine
      phosphorylation indirectly through the synthesis of an autocrine/paracrine
      factor. We further determined that the factor has heparin binding properties and
      identified the factor as midkine, a pleiotrophic growth factor previously
      associated with neuronal development and oncogenesis. Recombinant midkine induced
      STAT3 tyrosine phosphorylation in a time- and dose-dependent manner and
      stimulated the proliferation of postconfluent 3T3-L1 cells. Midkine neutralizing
      antibodies inhibited differentiation-induced STAT3 tyrosine phosphorylation as
      well as adipogenesis. These results show that MDI-induced synthesis and release
      of midkine explains the delayed activation of STAT3 during adipogenesis and that
      the midkine-STAT3 signaling pathway plays a necessary role in mitotic clonal
      expansion and differentiation.

PMID- 17204555
TI  - Identification of SH2B2beta as an inhibitor for SH2B1- and SH2B2alpha-promoted
      Janus kinase-2 activation and insulin signaling.
AB  - The SH2B family has three members (SH2B1, SH2B2, and SH2B3) that contain
      conserved dimerization (DD), pleckstrin homology, and SH2 domains. The DD domain
      mediates the formation of homo- and heterodimers between members of the SH2B
      family. The SH2 domain of SH2B1 (previously named SH2-B) or SH2B2 (previously
      named APS) binds to phosphorylated tyrosines in a variety of tyrosine kinases,
      including Janus kinase-2 (JAK2) and the insulin receptor, thereby promoting the
      activation of JAK2 or the insulin receptor, respectively. JAK2 binds to various
      members of the cytokine receptor family, including receptors for GH and leptin,
      to mediate cytokine responses. In mice, SH2B1 regulates energy and glucose
      homeostasis by enhancing leptin and insulin sensitivity. In this work, we
      identify SH2B2beta as a new isoform of SH2B2 (designated as SH2B2alpha) derived
      from the SH2B2 gene by alternative mRNA splicing. SH2B2beta has a DD and
      pleckstrin homology domain but lacks a SH2 domain. SH2B2beta bound to both SH2B1
      and SH2B2alpha, as demonstrated by both the interaction of glutathione S
      transferase-SH2B2beta fusion protein with SH2B1 or SH2B2alpha in vitro and
      coimmunoprecipitation of SH2B2beta with SH2B1 or SH2B2alpha in intact cells.
      SH2B2beta markedly attenuated the ability of SH2B1 to promote JAK2 activation and
      subsequent tyrosine phosphorylation of insulin receptor substrate-1 by JAK2.
      SH2B2beta also significantly inhibited SH2B1- or SH2B2alpha-promoted insulin
      signaling, including insulin-stimulated tyrosine phosphorylation of insulin
      receptor substrate-1. These data suggest that SH2B2beta is an endogenous
      inhibitor of SH2B1 and/or SH2B2alpha, negatively regulating insulin signaling
      and/or JAK2-mediated cellular responses.

PMID- 17204556
TI  - Does cortisol acting via the type II glucocorticoid receptor mediate suppression
      of pulsatile luteinizing hormone secretion in response to psychosocial stress?
AB  - This study assessed the importance of cortisol in mediating inhibition of
      pulsatile LH secretion in sheep exposed to a psychosocial stress. First, we
      developed an acute psychosocial stress model that involves sequential layering of
      novel stressors over 3-4 h. This layered-stress paradigm robustly activated the
      hypothalamic-pituitary-adrenal axis and unambiguously inhibited pulsatile LH
      secretion. We next used this paradigm to test the hypothesis that cortisol,
      acting via the type II glucocorticoid receptor (GR), mediates stress-induced
      suppression of pulsatile LH secretion. Our approach was to determine whether an
      antagonist of the type II GR (RU486) reverses inhibition of LH pulsatility in
      response to the layered stress. We used two animal models to assess different
      aspects of LH pulse regulation. With the first model (ovariectomized ewe), LH
      pulse characteristics could vary as a function of both altered GnRH pulses and
      pituitary responsiveness to GnRH. In this case, antagonism of the type II GR did
      not prevent stress-induced inhibition of pulsatile LH secretion. With the second
      model (pituitary-clamped ovariectomized ewe), pulsatile GnRH input to the
      pituitary was fixed to enable assessment of stress effects specifically at the
      pituitary level. In this case, the layered stress inhibited pituitary
      responsiveness to GnRH and antagonism of the type II GR reversed the effect.
      Collectively, these findings indicate acute psychosocial stress inhibits
      pulsatile LH secretion, at least in part, by reducing pituitary responsiveness to
      GnRH. Cortisol, acting via the type II GR, is an obligatory mediator of this
      effect. However, under conditions in which GnRH input to the pituitary is not
      clamped, antagonism of the type II GR does not prevent stress-induced inhibition
      of LH pulsatility, implicating an additional pathway of suppression that is
      independent of cortisol acting via this receptor.

PMID- 17204557
TI  - Daily rhythm in pineal phosphodiesterase (PDE) activity reflects adrenergic/3',5'
      cyclic adenosine 5'-monophosphate induction of the PDE4B2 variant.
AB  - The pineal gland is a photoneuroendocrine transducer that influences circadian
      and circannual dynamics of many physiological functions via the daily rhythm in
      melatonin production and release. Melatonin synthesis is stimulated at night by a
      photoneural system through which pineal adenylate cyclase is adrenergically
      activated, resulting in an elevation of cAMP. cAMP enhances melatonin synthesis
      through actions on several elements of the biosynthetic pathway. cAMP degradation
      also appears to increase at night due to an increase in phosphodiesterase (PDE)
      activity, which peaks in the middle of the night. Here, it was found that this
      nocturnal increase in PDE activity results from an increase in the abundance of
      PDE4B2 mRNA (approximately 5-fold; doubling time, approximately 2 h). The
      resulting level is notably higher (>6-fold) than in all other tissues examined,
      none of which exhibit a robust daily rhythm. The increase in PDE4B2 mRNA is
      followed by increases in PDE4B2 protein and PDE4 enzyme activity. Results from in
      vivo and in vitro studies indicate that these changes are due to activation of
      adrenergic receptors and a cAMP-dependent protein kinase A mechanism. Inhibition
      of PDE4 activity during the late phase of adrenergic stimulation enhances cAMP
      and melatonin levels. The evidence that PDE4B2 plays a negative feedback role in
      adrenergic/cAMP signaling in the pineal gland provides the first proof that cAMP
      control of PDE4B2 is a physiologically relevant control mechanism in cAMP
      signaling.

PMID- 17204559
TI  - Glucotoxicity inhibits late steps of insulin exocytosis.
AB  - Prolonged exposure of beta-cells to high glucose (glucotoxicity) diminishes
      insulin secretion in response to glucose and has been linked to altered
      generation of metabolism-secretion coupling factors. We have investigated whether
      glucotoxicity may also alter calcium handling and late steps in secretion such as
      exocytosis. Clonal INS-1E beta-cells cultured at high glucose (20 or 30 mM vs.
      5.5 mM) for 72 h exhibited elevated basal intracellular calcium ([Ca2+]i), which
      was KATP-channel dependent and due to long-term activation of protein kinase A.
      An increased amplitude and shortened duration of depolarization-evoked rises in
      [Ca2+]i were apparent. These changes were probably linked to the observed
      increased filling of intracellular stores and to short-term activation of protein
      kinase A. Insulin secretion was reduced not only by acute stimulation with either
      glucose or KCl but more importantly by direct calcium stimulation of
      permeabilized cells. These findings indicate a defect in the final steps of
      exocytosis. To confirm this, we measured expression levels of some 30 proteins
      implicated in trafficking/exocytosis of post-Golgi vesicles. Several proteins
      required for calcium-induced exocytosis of secretory granules were down
      regulated, such as the soluble N-ethylmaleimide-sensitive factor-sensitive factor
      attachment receptor (SNARE) proteins VAMP-2 [vesicle (v)-SNARE, vesicle
      associated membrane protein 2] and syntaxin 1 as well as complexin. VAMP-2 was
      also reduced in human islets. In contrast, cell immunostaining and expression
      levels of several fluorescent proteins suggested that other post-trans-Golgi
      trafficking steps and compartments are preserved and that cells were not
      degranulated. Thus, these studies indicate that, in addition to known metabolic
      changes, glucotoxicity impedes generation of signals for secretion and diminishes
      the efficiency of late steps in exocytosis.

PMID- 17204558
TI  - Daily limited access to sweetened drink attenuates hypothalamic-pituitary
      adrenocortical axis stress responses.
AB  - Stress can promote palatable food intake, and consumption of palatable foods may
      dampen psychological and physiological responses to stress. Here we develop a rat
      model of daily limited sweetened drink intake to further examine the linkage
      between consumption of preferred foods and hypothalamic-pituitary-adrenocortical
      axis responses to acute and chronic stress. Adult male rats with free access to
      water were given additional twice-daily access to 4 ml sucrose (30%), saccharin
      (0.1%; a noncaloric sweetener), or water. After 14 d of training, rats readily
      learned to drink sucrose and saccharin solutions. Half the rats were then given
      chronic variable stress (CVS) for 14 d immediately after each drink exposure; the
      remaining rats (nonhandled controls) consumed their appropriate drinking solution
      at the same time. On the morning after CVS, responses to a novel restraint stress
      were assessed in all rats. Multiple indices of chronic stress adaptation were
      effectively altered by CVS. Sucrose consumption decreased the plasma
      corticosterone response to restraint stress in CVS rats and nonhandled controls;
      these reductions were less pronounced in rats drinking saccharin. Sucrose or
      saccharin consumption decreased CRH mRNA expression in the paraventricular
      nucleus of the hypothalamus. Moreover, sucrose attenuated restraint-induced c-fos
      mRNA expression in the basolateral amygdala, infralimbic cortex, and claustrum.
      These data suggest that limited consumption of sweetened drink attenuates
      hypothalamic-pituitary-adrenocortical axis stress responses, and calories
      contribute but are not necessary for this effect. Collectively the results
      support the hypothesis that the intake of palatable substances represents an
      endogenous mechanism to dampen physiological stress responses.

PMID- 17204560
TI  - Overexpression of adiponectin targeted to adipose tissue in transgenic mice:
      impaired adipocyte differentiation.
AB  - Adiponectin (ApN) is an adipokine whose expression and plasma levels are
      inversely related to obesity and insulin-resistant states. Chronic repercussions
      of ApN treatment or overexpression on adiposity and body weight are still
      controversial. Here, we generated a transgenic (Tg) mouse model allowing
      persistent and moderate overexpression of native full-length ApN targeted to
      white adipose tissue. Adipose mass and adipocyte size of Tg mice were reduced
      despite preserved calorie intake. This reduction resulted from increased energy
      expenditure and up-regulation of uncoupling proteins, and from abrogation of the
      adipocyte differentiation program, as shown by the loss of a key lipogenic enzyme
      and of adipocyte markers. Adipose mass remodeling favors enhanced insulin
      sensitivity and improved lipid profile of Tg mice. Alteration of the adipocyte
      phenotype was likely to result from increased expression of the preadipocyte
      factor-1 and from down-regulation of the transcription factor, CCAAT/enhancer
      binding protein-alpha, which orchestrates adipocyte differentiation. We further
      found that recombinant ApN directly stimulated pre- adipocyte factor-1 mRNA and
      attenuated CCAAT/enhancer binding protein-alpha expression in cultured 3T3-F442A
      cells. Conversely, opposite changes in the expression of these genes were
      observed in white fat of ApN-deficient mice. Thus, besides enhanced energy
      expenditure, our work shows that impairment of adipocyte differentiation
      contributes to the anti-adiposity effect of ApN.

PMID- 17204561
TI  - A natural genetic code expansion cassette enables transmissible biosynthesis and
      genetic encoding of pyrrolysine.
AB  - Pyrrolysine has entered natural genetic codes by the translation of UAG, a
      canonical stop codon. UAG translation as pyrrolysine requires the pylT gene
      product, an amber-decoding tRNA(Pyl) that is aminoacylated with pyrrolysine by
      the pyrrolysyl-tRNA synthetase produced from the pylS gene. The pylTS genes form
      a gene cluster with pylBCD, whose functions have not been investigated. The
      pylTSBCD gene order is maintained not only in methanogenic Archaea but also in a
      distantly related Gram-positive Bacterium, indicating past horizontal gene
      transfer of all five genes. Here we show that lateral transfer of pylTSBCD
      introduces biosynthesis and genetic encoding of pyrrolysine into a naive
      organism. PylS-based assays demonstrated that pyrrolysine was biosynthesized in
      Escherichia coli expressing pylBCD from Methanosarcina acetivorans. Production of
      pyrrolysine did not require tRNA(Pyl) or PylS. However, when pylTSBCD were
      coexpressed with mtmB1, encoding the methanogen monomethylamine
      methyltransferase, UAG was translated as pyrrolysine to produce recombinant
      monomethylamine methyltransferase. Expression of pylTSBCD also suppressed an
      amber codon introduced into the E. coli uidA gene. Strains lacking one of the
      pylBCD genes did not produce pyrrolysine or translate UAG as pyrrolysine. These
      results indicated that pylBCD gene products biosynthesize pyrrolysine using
      metabolites common to Bacteria and Archaea and, furthermore, that the pyl gene
      cluster represents a "genetic code expansion cassette," previously unprecedented
      in natural organisms, whose transfer allows an existing codon to be translated as
      a novel endogenously synthesized free amino acid. Analogous cassettes may have
      served similar functions for other amino acids during the evolutionary expansion
      of the canonical genetic code.

PMID- 17204562
TI  - Motifs for molecular recognition exploiting hydrophobic enclosure in protein
      ligand binding.
AB  - The thermodynamic properties and phase behavior of water in confined regions can
      vary significantly from that observed in the bulk. This is particularly true for
      systems in which the confinement is on the molecular-length scale. In this study,
      we use molecular dynamics simulations and a powerful solvent analysis technique
      based on inhomogenous solvation theory to investigate the properties of water
      molecules that solvate the confined regions of protein active sites. Our
      simulations and analysis indicate that the solvation of protein active sites that
      are characterized by hydrophobic enclosure and correlated hydrogen bonds induce
      atypical entropic and enthalpic penalties of hydration. These penalties
      apparently stabilize the protein-ligand complex with respect to the independently
      solvated ligand and protein, which leads to enhanced binding affinities. Our
      analysis elucidates several challenging cases, including the super affinity of
      the streptavidin-biotin system.

PMID- 17204563
TI  - Regulation of epithelial tight junction assembly and disassembly by AMP-activated
      protein kinase.
AB  - AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that
      plays an important role in maintaining cellular energy balance. The activity of
      AMPK is modulated both by the cellular AMP-to-ATP ratio and by upstream kinases.
      Recently, AMPK was shown to be phosphorylated and activated by LKB1, a protein
      kinase that plays a conserved role in epithelial polarity regulation in mammals
      and Drosophila. Here, we investigate the involvement of AMPK in the regulation of
      epithelial tight junction assembly and cell polarization in MDCK cells. We show
      that the level of AMPK phosphorylation increases during calcium-induced tight
      junction assembly and cell polarization and that this increase depends on the
      kinase activity of LKB1. Expression of a kinase-dead mutant of AMPK inhibits
      tight junction assembly as indicated by measurement of transepithelial resistance
      and analysis of ZO-1 localization to the tight junction after calcium switch.
      Conversely, 5-aminoimidizole-4-carboxamide riboside, an activator of AMPK,
      promotes transepithelial resistance development and tight junction assembly upon
      calcium switch. Furthermore, 5-aminoimidizole-4-carboxamide riboside partially
      protects the tight junctions from disassembly induced by calcium depletion. These
      results support an important role of AMPK in the regulation of epithelial tight
      junction assembly and disassembly and suggest an intriguing link between cellular
      energy status and tight junction function.

PMID- 17204564
TI  - Antimalarials may influence the risk of malignancy in systemic lupus
      erythematosus.
AB  - BACKGROUND: Recent studies suggest that antimalarials have antineoplastic
      properties. OBJECTIVE: To investigate whether antimalarials decrease the risk of
      cancer in systemic lupus erythematosus (SLE). METHODS: An observational
      prospective cohort study was carried out. 235 patients were included in the study
      at the time of diagnosis (American College of Rheumatology criteria). The end
      point was the diagnosis of cancer. Kaplan-Meier cancer-free survival curves for
      patients treated and not treated with antimalarials were compared. A Cox
      proportional hazards model was fitted, with cancer as the dependent variable. Age
      at diagnosis, gender, treatment with azathioprine, cyclophosphamide and
      methotrexate, smoking, Systemic Lupus International Collaborating Clinics (SLICC)
      Damage Index 6 months after diagnosis, year of diagnosis and treatment with
      antimalarials were entered as independent variables. RESULTS: 209 (89%) patients
      were women. 233 (99%) patients were white. Mean (SD) age at diagnosis was 37 (16)
      years. Median (range) follow-up was 10 (1-31) years. 156 (66%) patients had ever
      received antimalarials. 2/156 (1.3%) ever-treated patients compared with 11/79
      (13%) never-treated patients had cancer (p<0.001). Cumulative cancer-free
      survival in treated and not treated patients was 0.98 and 0.73, respectively
      (p<0.001). Adjusted hazard ratio for cancer among malaria drug users compared
      with non-users was 0.15 (95% CI 0.02 to 0.99). CONCLUSIONS: This study launches
      the hypothesis of a protective action of antimalarials against cancer in patients
      with SLE. This effect should be confirmed in larger multicentre studies.

PMID- 17204565
TI  - The public neglect of rheumatic diseases: insights from analyses of attendees in
      a musculoskeletal disease awareness activity.
AB  - OBJECTIVES: To obtain data on the care received by individuals counselled during
      a public health awareness campaign on painful musculoskeletal conditions (MSC).
      METHODS: Easy non-formal access to rheumatologists/pain specialists was offered
      using a mobile unit (Rheuma-Bus) at widely accessible sites. Clients were asked
      to assess their severity of pain using a 100 mm visual analogue scale (VAS). Age,
      gender, disease duration, diagnosis if known, current and previous treatment as
      well as tentative diagnoses assigned and recommendations given to each individual
      by the counselling physicians were recorded. RESULTS: Average (SD) VAS pain
      rating was 59 (20.6) mm. Approximately 40% of clients had never consulted a
      physician for their condition before, but had lower pain scores than those who
      had seen a physician. Patients with inflammatory MSC had higher pain scores than
      those with non-inflammatory conditions. More than 2% of the clients had a newly
      detected inflammatory rheumatic disease. CONCLUSIONS: Many individuals having
      painful MSC seek medical help only when a very high threshold of pain is reached.
      Even while under treatment, the high mean pain scores suggest neglect of MSC that
      are not adequately recognised as important contributors to disability and
      decreased quality of life.

PMID- 17204566
TI  - Effect of chondroitin sulphate in symptomatic knee osteoarthritis: a multicentre,
      randomised, double-blind, placebo-controlled study.
AB  - OBJECTIVE: To evaluate the efficacy and tolerability of chondroitin sulphate
      (chondroitin sulphate) in knee osteoarthritis. PATIENTS AND METHODS: A 24-week,
      randomised placebo-controlled trial of chondroitin sulphate (1 g/day) in patients
      with symptomatic knee osteoarthritis as measured on a visual analogue scale. Pain
      on daily activities and Lequesne's Index were the primary efficacy criteria.
      Secondary outcomes included the rate of responders according to the outcome
      measures in rheumatoid arthritis clinical trials of the Osteoarthritis Research
      Society International (OMERACT-OARSI) criteria, quality of life,
      patient's/physician's global assessments and carry-over effect after treatment.
      Biochemical markers of bone (CTX-I), cartilage (CTX-II) and synovium (hyaluronic
      acid) metabolism were also measured. Safety was assessed by recording adverse
      events (AEs). Statistical analysis was performed on the inter-group differences
      in the intention-to-treat population. RESULTS: 307 patients were included in the
      study. 28 (9%) patients discontinued the study because of lack of efficacy or
      AEs. At the end of treatment, the decrease in pain was -26.2 (24.9) and -19.9
      (23.5) mm and improved function was -2.4 (3.4) (-25%) and -1.7 (3.3) (-17%) in
      the chondroitin sulphate and placebo groups, respectively (p = 0.029 and 0.109).
      The OMERACT-OARSI responder rate was 68% in the chondroitin sulphate and 56% in
      the placebo group (p = 0.03). The investigator's assessments and short form 12
      (SF-12) physical component reported improvement more frequently in the
      chondroitin sulphate than in the placebo group (p = 0.044 and 0.021,
      respectively). No significant difference was observed between treatment groups
      for changes in biomarkers over 24 weeks. However, there was a significant
      difference between non-responders and responders according to the OARSI criteria
      for 24-week changes of CTX-I (p = 0.018) and CTX-II (p = 0.014). Tolerance was
      considered to be satisfactory. CONCLUSION: This study failed to show an efficacy
      of chondroitin sulphate on the two primary criteria considered together, although
      chondroitin sulphate was slightly more effective than placebo on pain, OMERACT
      OARSI response rate, investigator's assessment and quality of life.

PMID- 17204567
TI  - Effect of weight reduction in obese patients diagnosed with knee osteoarthritis:
      a systematic review and meta-analysis.
AB  - This review aims to assess by meta-analysis of randomised controlled trials
      (RCTs) changes in pain and function when overweight patients with knee
      osteoarthritis (OA) achieve a weight loss. Systematic searches were performed and
      reference lists from the retrieved trials were searched. RCTs were enclosed in
      the systematic review if they explicitly stated diagnosis of knee OA and reported
      a weight change as the only difference in intervention from the control group.
      Outcome Measures for Arthritis Clinical Trials III outcome variables were
      considered for analysis. Effect size (ES) was calculated using RevMan, and meta
      regression analyses were performed using weighted estimates from the random
      effects analyses. Among 35 potential trials identified, four RCTs including five
      intervention/control groups met our inclusion criteria and provided data from 454
      patients. Pooled ES for pain and physical disability were 0.20 (95% CI 0 to 0.39)
      and 0.23 (0.04 to 0.42) at a weight reduction of 6.1 kg (4.7 to 7.6 kg). Meta
      regression analysis showed that disability could be significantly improved when
      weight was reduced over 5.1%, or at the rate of >0.24% reduction per week.
      Clinical efficacy on pain reduction was present, although not predictable after
      weight loss. Meta-regression analysis indicated that physical disability of
      patients with knee OA and overweight diminished after a moderate weight reduction
      regime. The analysis supported that a weight loss of >5% should be achieved
      within a 20-week period--that is, 0.25% per week.

PMID- 17204568
TI  - Chimeric antibodies to proteinase 3 of IgG1 and IgG3 subclasses induce different
      magnitudes of functional responses in neutrophils.
AB  - BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCA) are associated with
      small-vessel vasculitis and have been implicated in its pathogenesis. The
      subclass distribution of ANCA IgG deviates from normal patterns, and it has been
      suggested that the IgG3 subclass may have pathogenic potential over the IgG1
      subclass and may be more likely to be associated with active disease and renal
      involvement. OBJECTIVE: To deal with potential pathogenicity, chimeric antibodies
      were constructed of IgG1 and three subclasses with human IgG1 or three constant
      regions and a murine-derived variable region that binds an epitope within the
      ANCA antigen proteinase 3 (PR3) that is recognised by human autoantibodies.
      METHODS: The antibodies were characterised for binding to PR3, including affinity
      and avidity, before being used as tools to explore their ability to activate
      human neutrophils for superoxide release, cytokine release, degranulation and
      ability to induce neutrophil adhesion under flow. RESULTS: Both subclass
      antibodies elicited similar neutrophil responses for superoxide release,
      degranulation and interleukin (IL) 8 production, although quantitative responses
      showed that the IgG1 subclass favoured degranulation and the IgG3 subclass
      favoured IL8 production. Both antibodies were able to convert neutrophils from
      selectin-dependent rolling adhesion to integrin-dependent stationary adhesion in
      a flow assay. CONCLUSIONS: These findings indicate that humanised antibodies
      directed against a single epitope of PR3 can recapitulate the effects of
      polyclonal human ANCA, which recognises multiple PR3 epitopes. Further, PR3-ANCA
      of both IgG1 and IgG3 subclasses can activate neutrophils, although the more
      potent IL8 response by IgG3 PR3-ANCA may encourage further neutrophil recruitment
      and amplify injury.

PMID- 17204569
TI  - Effects of airway distension on leukocyte recruitment in the mouse tracheal
      microvasculature.
AB  - We have shown previously that excessive distention of the rat trachea during
      mechanical ventilation results in enhanced leukocyte recruitment to the airway
      (Lim LH and Wagner EM. Am J Respir Crit Care Med 168:1068-1074, 2003). The
      objectives of this study were to develop a mouse model of positive end-expiratory
      pressure (PEEP)-induced leukocyte recruitment to the airway and begin to pursue
      molecular mechanisms that may contribute to the in vivo observation of increased
      leukocyte adhesion after PEEP exposure. We studied C57BL/6 wild-type mice and
      mice deficient in P-selectin or intercellular adhesion molecule-1 (ICAM-1)
      exposed to intermittent PEEP (8 cmH(2)O) applied five times for a 1-min duration,
      at 10-min intervals. After the imposed ventilatory stress, during normal
      ventilation (0.2 ml/breath, no PEEP), leukocyte adhesion in tracheal
      postcapillary venules was determined using intravital microscopy. PEEP induced a
      time-dependent increase in leukocyte adhesion that was significantly increased
      between 0 and 60 min (P < 0.01). Furthermore, PEEP-induced leukocyte adhesion at
      60 min was ablated in P-selectin- and ICAM-1-deficient mice. These findings
      demonstrate the essential nature of both P-selectin and ICAM-1 within airway
      postcapillary venular endothelium for leukocyte recruitment after airway
      distension.

PMID- 17204570
TI  - Metabolic acidosis inhibits hypothalamic warm-sensitive receptors: a potential
      causative factor in heat stroke.

PMID- 17204572
TI  - Postactivation potentiation in a human muscle: effect on the rate of torque
      development of tetanic and voluntary isometric contractions.
AB  - Postactivation potentiation (PAP), a mechanism by which the torque of a muscle
      twitch is increased following a conditioning contraction, is well documented in
      muscular physiology, but little is known about its effect on the maximal rate of
      torque development and functional significance during voluntary movements. The
      objective of this study was to investigate the PAP effect on the rate of
      isometric torque development of electrically induced and voluntary contractions.
      To that purpose, the electromechanical responses of the thumb adductor muscles to
      a single electrical stimulus (twitch), a train of 15 pulses at 250 Hz (HFT(250)),
      and during ballistic (i.e., rapid torque development) voluntary contractions at
      torque levels ranging from 10 to 75% of maximal voluntary contraction (MVC) were
      recorded before and after a conditioning 6-s MVC. The results showed that the
      rate of torque development was significantly (P < 0.001) increased after the
      conditioning MVC, but the effect was greater for the twitch ( approximately 200%)
      compared with the HFT(250) ( approximately 17%) or ballistic contractions (range:
      9-24%). Although twitch potentiation was maximal immediately after the
      conditioning MVC, maximal potentiation for HFT(250) and ballistic contractions
      was delayed to 1 min after the 6-s MVC. Furthermore, the similar degree of
      potentiation for the rate of isometric torque development between tetanic and
      voluntary ballistic contractions indicates that PAP is not related to the
      modality of muscle activation. These observations suggest that PAP may be
      considered as a mechanism that can influence our contractions during daily tasks
      and can be utilized to improve muscle performance in explosive sports.

PMID- 17204573
TI  - STAT3 signaling is activated in human skeletal muscle following acute resistance
      exercise.
AB  - The transcription factor signal transducer and activator of transcription 3
      (STAT3) has been identified as a mediator of cytokine signaling and implicated in
      hypertrophy; however, the importance of this pathway following resistance
      exercise in human skeletal muscle has not been investigated. In the present
      study, the phosphorylation and nuclear localization of STAT3, together with STAT3
      regulated genes, were measured in the early recovery period following intense
      resistance exercise. Muscle biopsy samples from healthy subjects (7 males, 23.0 +
      0.9 yr) were harvested before and again at 2, 4, and 24 h into recovery following
      a single bout of maximal leg extension exercise (3 sets, 12 repetitions). Rapid
      and transient activation of phosphorylated (tyrosine 705) STAT3 was observed at 2
      h postexercise. STAT3 phosphorylation paralleled the transient localization of
      STAT3 to the nucleus, which also peaked at 2 h postexercise. Downstream
      transcriptional events regulated by STAT3 activation peaked at 2 h postexercise,
      including early responsive genes c-FOS (800-fold), JUNB (38-fold), and c-MYC (140
      fold) at 2 h postexercise. A delayed peak in VEGF (4-fold) was measured 4 h
      postexercise. Finally, genes associated with modulating STAT3 signaling were also
      increased following exercise, including the negative regulator SOCS3 (60-fold).
      Thus, following a single bout of intense resistance exercise, a rapid
      phosphorylation and nuclear translocation of STAT3 are evident in human skeletal
      muscle. These data suggest that STAT3 signaling is an important common element
      and may contribute to the remodeling and adaptation of skeletal muscle following
      resistance exercise.

PMID- 17204574
TI  - 8-Oxoguanosine and uracil repair of nuclear and mitochondrial DNA in red and
      white skeletal muscle of exercise-trained old rats.
AB  - Oxoguanine DNA glycosylase (OGG1) and uracil DNA glycosylase (UDG) are two of the
      most important repair enzymes that are involved in the base excision repair
      processes to eliminate oxidative damage from mammalian DNA, which accumulates
      with aging. Red and white skeletal muscle fibers have very different antioxidant
      enzyme activities and resistance to oxidative stress. In this paper, we
      demonstrate that the activity of OGG1 is significantly higher in the red type of
      skeletal muscle compared with white fibers from old rats. Exercise training
      resulted in increased OGG1 activity in the nuclei of red fibers and decreased
      activity in nuclei of white fibers and in the mitochondria of both red and white
      fibers. The activities of UDG were similar in both red and white muscle fibers.
      Exercise training appears to increase the activity of UDG in the nuclei and
      mitochondria. However, exercise training affects the activity of OGG1 in nuclei
      and mitochondria differently, suggesting different regulation of the enzymes. In
      contrast, UDG showed similar activities in nuclei and mitochondrial extracts of
      exercise-trained animals. These data provide evidence for differential regulation
      of UDG and OGG1 in maintaining fidelity of DNA in oxidatively stressed cells.

PMID- 17204575
TI  - Parenchymal tethering, airway wall stiffness, and the dynamics of
      bronchoconstriction.
AB  - We do not yet have a good quantitative understanding of how the force-velocity
      properties of airway smooth muscle interact with the opposing loads of
      parenchymal tethering and airway wall stiffness to produce the dynamics of
      bronchoconstriction. We therefore developed a two-dimensional computational model
      of a dynamically narrowing airway embedded in uniformly elastic lung parenchyma
      and compared the predictions of the model to published measurements of airway
      resistance made in rats and rabbits during the development of bronchoconstriction
      following a bolus injection of methacholine. The model accurately reproduced the
      experimental time-courses of airway resistance as a function of both lung
      inflation pressure and tidal volume. The model also showed that the stiffness of
      the airway wall is similar in rats and rabbits, and significantly greater than
      that of the lung parenchyma. Our results indicate that the main features of the
      dynamical nature of bronchoconstriction in vivo can be understood in terms of the
      classic Hill force-velocity relationship operating against elastic loads provided
      by the surrounding lung parenchyma and an airway wall that is stiffer than the
      parenchyma.

PMID- 17204576
TI  - Age-related changes in multifinger synergies in accurate moment of force
      production tasks.
AB  - The purpose of this investigation was to document and quantify age-related
      differences in the coordination of fingers during a task that required production
      of an accurate time profile of the total moment of force by the four fingers of a
      hand. We hypothesized that elderly subjects would show a decreased ability to
      stabilize a time profile of the total moment of force, leading to larger indexes
      of moment variability compared with young subjects. The subjects followed a
      trapezoidal template on a computer screen by producing a time profile of the
      total moment of force while pressing down on force sensors with the four fingers
      of the right (dominant) hand. To quantify synergies, we used the framework of the
      uncontrolled manifold hypothesis. The elderly subjects produced larger total
      force, larger variance of both total force and total moment of force, and larger
      involvement of fingers that produced moment of force against the required moment
      direction (antagonist moment). This was particularly prominent during supination
      efforts. Young subjects showed covariation of commands to fingers across trials
      that stabilized the moment of total force (moment-stabilizing synergy), while
      elderly subjects failed to do so. Both subject groups showed similar indexes of
      covariation of commands to the fingers that stabilized the time profile of the
      total force. The lack of moment-stabilizing synergies may be causally related to
      the documented impairment of hand function with age.

PMID- 17204577
TI  - Vasopressin-induced vasoconstriction: two concentration-dependent signaling
      pathways.
AB  - Current scientific literature generally attributes the vasoconstrictor effects of
      [Arg(8)]vasopressin (AVP) to the activation of phospholipase C (PLC) and
      consequent release of Ca(2+) from the sarcoplasmic reticulum. However, half
      maximal activation of PLC requires nanomolar concentrations of AVP, whereas
      vasoconstriction occurs when circulating concentrations of AVP are orders of
      magnitude lower. Using cultured vascular smooth muscle cells, we previously
      identified a novel Ca(2+) signaling pathway activated by 10-100 pM AVP. This
      pathway is distinguished from the PLC pathway by its dependence on protein kinase
      C (PKC) and L-type voltage-sensitive Ca(2+) channels (VSCC). In the present
      study, we used isolated, pressurized rat mesenteric arteries to examine the
      contributions of these different Ca(2+) signaling mechanisms to AVP-induced
      vasoconstriction. AVP (10(-14)-10(-6) M) induced a concentration-dependent
      constriction of arteries that was reversible with a V(1a) vasopressin receptor
      antagonist. Half-maximal vasoconstriction at 30 pM AVP was prevented by blockade
      of VSCC with verapamil (10 microM) or by PKC inhibition with calphostin-C (250
      nM) or Ro-31-8220 (1 microM). In contrast, acute vasoconstriction induced by 10
      nM AVP (maximal) was insensitive to blockade of VSCC or PKC inhibition. However,
      after 30 min, the remaining vasoconstriction induced by 10 nM AVP was partially
      dependent on PKC activation and almost fully dependent on VSCC. These results
      suggest that different Ca(2+) signaling mechanisms contribute to AVP-induced
      vasoconstriction over different ranges of AVP concentration. Vasoconstrictor
      actions of AVP, at concentrations of AVP found within the systemic circulation,
      utilize a Ca(2+) signaling pathway that is dependent on PKC activation and can be
      inhibited by Ca(2+) channel blockers.

PMID- 17204578
TI  - Intracellular PO2 kinetics at different contraction frequencies in Xenopus single
      skeletal muscle fibers.
AB  - Increasing contraction frequency in single skeletal muscle fibers has been shown
      to increase the magnitude of the fall in intracellular Po(2) (Pi(O(2))),
      reflecting a greater metabolic rate. To test whether Pi(O(2)) kinetics are
      altered by contraction frequency through this increase in metabolic stress,
      Pi(O(2)) was measured in Xenopus single fibers (n = 11) during and after
      contraction bouts at three different frequencies. Pi(O(2)) was measured via
      phosphorescence quenching at 0.16-, 0.25-, and 0.5-Hz tetanic stimulation. The
      kinetics of the change in Pi(O(2)) from resting baseline to end-contraction
      values and end contraction to rest were described as a mean response time (MRT)
      representing the time to 63% of the change in Pi(O(2)). As predicted, the fall in
      Pi(O(2)) from baseline following contractions was progressively greater at 0.5
      and 0.25 Hz than at 0.16 Hz (32.8 +/- 2.1 and 29.3 +/- 2.0 Torr vs. 23.6 +/- 2.2
      Torr, respectively) since metabolic demand was greater. The MRT for the decrease
      in Pi(O(2)) was progressively faster at the higher frequencies (0.5 Hz: 45.3 +/-
      4.5 s; 0.25 Hz: 63.3 +/- 4.1 s; 0.16 Hz: 78.0 +/- 4.1 s), suggesting faster
      accumulation of stimulators of oxidative phosphorylation. The MRT for Pi(O(2))
      off-kinetics (0.5 Hz: 84.0 +/- 11.7 s; 0.25 Hz: 79.1 +/- 8.4 s; 0.16 Hz: 81.1 +/-
      8.3 s) was not different between trials. These data demonstrate in single fibers
      that the rate of the fall in Pi(O(2)) is dependent on contraction frequency,
      whereas the rate of recovery following contractions is independent of either the
      magnitude of the fall in Pi(O(2)) from baseline or the contraction frequency.
      This suggests that stimulation frequency plays an integral role in setting the
      initial metabolic response to work in isolated muscle fibers, possibly due to
      temporal recovery between contractions, but it does not determine recovery
      kinetics.

PMID- 17204579
TI  - Progenitor cells and age: can we fight aging with exercise?

PMID- 17204581
TI  - involvement of microsomal epoxide hydrolase enzyme in ovotoxicity caused by 7,12
      dimethylbenz[a]anthracene.
AB  - Ovarian follicle disruption in mice caused by 7,12-dimethylbenz[a]anthracene
      (DMBA) is attributed to its bioactivation by CYP1B1 to a 3,4-epoxide which is
      then hydrolyzed to form a 3,4-diol by microsomal epoxide hydrolase (mEH). Further
      epoxidation by CYP1A1 or 1B1 forms the ultimate ovotoxicant, DMBA-3,4-diol-1,2
      epoxide. Studies suggest that the mouse ovary expresses these enzymes, and thus,
      may be capable of bioactivating DMBA to its ovotoxic metabolite. The present
      study was designed to evaluate the role of ovarian mEH in DMBA-induced
      ovotoxicity using a novel neonatal mouse ovarian culture system. Ovaries from
      postnatal day (PND) 4 B6C3F(1) mice were incubated with DMBA (12.5 nM-1 microM)
      for various lengths of time. Following incubation, ovaries were histologically
      evaluated or assessed for mEH protein or mRNA. Following 15 days of incubation,
      DMBA reduced (p < 0.05) healthy follicles at concentrations >or= 12.5 nM. At 1
      microM DMBA, follicle loss and increased mEH protein were measured (p < 0.05) by
      6 h. mRNA encoding mEH markedly increased after 2 days of incubation, and this
      increase preceded accelerated follicle loss at 4 days. Furthermore, follicle loss
      induced by DMBA was prevented when cyclohexene oxide (2mM), an mEH inhibitor, was
      added to DMBA incubations. These studies suggest that the PND4 mouse ovary is
      capable of bioactivating DMBA to its ovotoxic form, and that ovarian mEH enzyme
      activity is likely involved. Furthermore, these observations support the use of a
      novel ovarian culture system to study ovary-specific metabolism of xenobiotic
      chemicals.

PMID- 17204582
TI  - Diethanolamine alters proliferation and choline metabolism in mouse neural
      precursor cells.
AB  - Diethanolamine (DEA) is a widely used ingredient in many consumer products and in
      a number of industrial applications. It has been previously reported that dermal
      administration of DEA to mice diminished hepatic stores of choline and altered
      brain development in the fetus. The aim of this study was to use mouse neural
      precursor cells in vitro to assess the mechanism underlying the effects of DEA.
      Cells exposed to DEA treatment (3mM) proliferated less (by 5-bromo-2-deoxyuridine
      incorporation) at 48 h (24% of control [CT]), and had increased apoptosis at 72 h
      (308% of CT). Uptake of choline into cells was reduced by DEA treatment (to 52%
      of CT), resulting in diminished intracellular concentrations of choline and
      phosphocholine (55 and 12% of CT, respectively). When choline concentration in
      the growth medium was increased threefold (to 210 microM), the effects of DEA
      exposure on cell proliferation and apoptosis were prevented, however,
      intracellular phosphocholine concentrations remained low. In choline kinase
      assays, we observed that DEA can be phosphorylated to phospho-DEA at the expense
      of choline. Thus, the effects of DEA are likely mediated by inhibition of choline
      transport into neural precursor cells and by altered metabolism of choline. Our
      study suggests that prenatal exposure to DEA may have a detrimental effect on
      brain development.

PMID- 17204583
TI  - Developmental exposure to methylmercury alters learning and induces depression
      like behavior in male mice.
AB  - To investigate the long-term effects of developmental exposure to methylmercury
      (MeHg), pregnant mice were exposed to at 0.5 mg MeHg/kg/day via drinking water
      from gestational day 7 until day 7 after delivery. The behavior of offspring was
      monitored at 5-15 and 26-36 weeks of age using an automated system (IntelliCage)
      designed for continuous long-term recording of the home cage behavior in social
      groups and complex analysis of basic activities and learning. In addition,
      spontaneous locomotion, motor coordination on the accelerating rotarod, spatial
      learning in Morris water maze, and depression-like behavior in forced swimming
      test were also studied. The analysis of behavior performed in the IntelliCage
      without social deprivation occurred to be more sensitive in detecting alterations
      in activity and learning paradigms. We found normal motor function but decreased
      exploratory activity in MeHg-exposed male mice, especially at young age. Learning
      disturbances observed in MeHg-exposed male animals suggest reference memory
      impairment. Interestingly, the forced swimming test revealed a predisposition to
      depressive-like behavior in the MeHg-exposed male offspring. This study provides
      novel evidence that the developmental exposure to MeHg can affect not only
      cognitive functions but also motivation-driven behaviors.

PMID- 17204584
TI  - Genetic toxicity assessment: employing the best science for human safety
      evaluation part III: the comet assay as an alternative to in vitro clastogenicity
      tests for early drug candidate selection.
AB  - Early screening of drug candidates for genotoxicity typically includes an
      analysis for mutagenicity in bacteria and for clastogenicity in cultured
      mammalian cells. In addition, in recent years, an early assessment of
      photogenotoxicity potential has become increasingly important. Also, for
      screening purposes, expert computer systems can be used to identify structural
      alerts. In cases where structural alerts are identified, mutagenicity testing
      limited to bacteria can be conducted. The sequence of computer-aided analysis and
      limited testing using bacteria allows for screening a comparatively large number
      of drug candidates. In contrast, considerably more resources, in terms of
      supplies, technical time, and the amount of a test substance needed, are required
      when screening for clastogenic activity in mammalian cells. In addition, the
      relatively large percentage of false positive results for rodent carcinogenicity
      associated with clastogenicity assays is of considerable concern. As a
      consequence, mammalian cell-based alternatives to clastogenicity assays are
      needed for early screening of mammalian genotoxicity. The comet assay is a
      relatively fast, simple, and sensitive technique for the analysis of DNA damage
      in mammalian cells. This assay seems especially useful for screening purposes
      because false positives associated with excessive toxicity appear to occur less
      frequently, only relatively small amounts of a test compound are needed, and
      certain steps of the test procedure can be automated. Therefore, the in vitro
      comet assay is proposed as an alternative to cytogenetic assays in early
      genotoxicity/photogenotoxicity screening of drug candidates.

PMID- 17204585
TI  - Inhibitory kappaB kinase 2 activates airway epithelial cells to stimulate bone
      marrow macrophages.
AB  - It has not been resolved whether macrophages or airway epithelial cells primarily
      respond to infectious and inflammatory stimuli and initiate a cell-to-cell
      inflammatory interaction within the airways. We hypothesized that the airway
      epithelial cells are primary responders that activate macrophages in response to
      environmental stimuli. To investigate the unilateral contribution of airway
      epithelial cells in the activation of macrophages, we developed an in vitro
      system in which the primary mouse tracheal epithelial cells (MTEC) and primary
      bone marrow-derived macrophages (BMDM) were incubated together for a brief period
      of time in a Transwell culture plate. MTEC were transfected with adenoviral
      vectors that express a constitutively active form of IKK2 (Ad-cIKK2), Ad-beta
      Gal, or PBS for 48 h before incubating with the macrophages. Macrophage
      activation was determined by measuring surface expression of CD11b, activation of
      NF-kappaB, phagocytic activity and production of reactive oxygen species, and
      cyclooxygenase (COX)-2 gene expression and production of prostaglandins.
      Macrophage adherence to epithelial layer was confirmed by CD68 immunostaining and
      scanning electron microscopy. MTEC cells transfected with Ad-cIKK2 produced
      increased amounts of IL-6, mouse GRO-alpha, TNF-alpha, and prostaglandin (PG)E2.
      Exposure of BMDM to MTEC, transfected with Ad-cIKK2, led to an increase in the
      CD11b expression and increased adherence of macrophages to the epithelial cell
      layer. NF-kappaB activation, COX-2 gene expression, and PGD2 synthesis were also
      increased in BMDM that were incubated with MTEC transfected with Ad-cIKK2. These
      data suggest that airway epithelial cells potentially play a primary role in
      generating inflammatory signals that result in activation of macrophages.

PMID- 17204586
TI  - Head, face, and eye injuries in scholastic and collegiate lacrosse: a 4-year
      prospective study.
AB  - BACKGROUND: Risks and mechanisms of head, face, and eye injuries in high school
      and college lacrosse are not well documented. PURPOSE: To identify (1) primary
      mechanisms of head, face, and eye injuries in lacrosse and (2) differences in
      injury risk between the men's and women's game and between high school and
      collegiate levels. STUDY DESIGN: Descriptive epidemiological study. METHODS: The
      authors gathered data on 507,000 girls' and boys' high school and 649,573 women's
      and men's college lacrosse athletic exposures using sport-specific injury
      surveillance systems over 4 seasons. They identified the most common scenarios
      for head, face, and eye injuries. RESULTS: The high school girls' head, face, and
      eye injury rate (0.54 per 1000 athletic exposures) was significantly higher
      (incident rate ratio, 1.42; 95% confidence interval, 1.09-1.86) than that for
      boys (0.38 per 1000 athletic exposures); college women (0.77 per 1000 athletic
      exposures) sustained a higher rate of injuries (incident rate ratio, 1.76; 95%
      confidence interval, 1.42-2.19) than did men (0.44 per 1000 athletic exposures).
      Concussions constituted a higher percentage of injuries among boys (73%) and men
      (85%) than among girls (40%) and women (41%). Men sustained few facial injuries,
      whereas a substantial proportion of women's injuries involved the face and
      orbital area. CONCLUSION: Although permitting only incidental contact, women's
      lacrosse had higher rates of head, face, and eye injuries at both the high school
      and collegiate levels. Concussion was the most common injury. For men, the
      primary injury mechanism was player-to-player contact; women's injuries primarily
      resulted from stick or ball contact. High school injury rates were lower than
      were college rates, but the nature of injuries, body parts affected, and
      mechanisms were similar.

PMID- 17204587
TI  - Intraosseous innervation of the human patella: a histologic study.
AB  - BACKGROUND: The soft tissue structures surrounding the human knee joint have been
      the subject of extensive anatomic study. The detailed histologic findings within
      the bone of the human patella, however, have not been systematically studied.
      While the nerves supplied to the periarticular soft tissues have been very well
      documented, the nerves supplied to the interior of the bony patella have never
      been described. HYPOTHESIS: This study tests the hypothesis that the patella
      contains an intraosseous nerve network. Further, the authors investigate the
      anatomic location of these intraosseous nerves to better understand their
      possible clinical relevance. STUDY DESIGN: Descriptive laboratory study. METHODS:
      Ten matched pairs of cadaveric patellae (left and right patellae from the same
      individual; 20 total) were prepared for evaluation by hematoxylin and eosin
      staining using a technique that allows the creation of complete, large histologic
      sections of individual patellae. The matched specimens were dissected free of
      soft tissue and then sectioned using a diamond-wafering saw into 3-mm sagittal
      (left patella) and transverse (right patella) sections. Sections were then
      decalcified and whole-mounted into paraffin blocks for further sectioning using a
      large-format microtome. All 20 specimens were prepared for evaluation. Age at
      death averaged 80 years (range, 64-91). All specimens demonstrated at least grade
      II chondromalacia. RESULTS: Nineteen of 20 (95%) specimens demonstrated
      intraosseous nerves. Of 248 sections studied, 116 (47%) demonstrated intraosseous
      nerves, with 227 individual nerves identified. The density of intraosseous nerves
      was greatest in the medial and central portions of the patella, with a
      significant paucity identified laterally. CONCLUSION: The primary intraosseous
      innervation of the patella derives from a medially based neurovascular bundle.
      CLINICAL RELEVANCE: A better understanding of the nerves within the human bony
      patella may improve understanding the patho-physiology of anterior knee pain
      syndromes.

PMID- 17204588
TI  - V-H+ -ATPase translocation during blood alkalosis in dogfish gills: interaction
      with carbonic anhydrase and involvement in the postfeeding alkaline tide.
AB  - We investigated the involvement of carbonic anhydrase (CA) in mediating V-H(+)
      ATPase translocation into the basolateral membrane in gills of alkalotic Squalus
      acanthias. Immunolabeling revealed that CA is localized in the same cells as V
      H(+)-ATPase. Blood plasma from dogfish injected with acetazolamide [30 mg/kg at
      time (t) = 0 and 6 h] and infused with NaHCO(3) for 12 h (1,000 microeq.kg(-1).h(
      1)) had significantly higher plasma HCO(3)(-) concentration than fish that were
      infused with NaHCO(3) alone (28.72 +/- 0.41 vs. 6.57 +/- 2.47 mmol/l, n = 3),
      whereas blood pH was similar in both treatments (8.03 +/- 0.11 vs. 8.04 +/- 0.11
      pH units at t = 12 h). CA inhibition impaired V-H(+)-ATPase translocation into
      the basolateral membrane, as estimated from immunolabeled gill sections and
      Western blotting on gill cell membranes (0.24 +/- 0.08 vs. 1.00 +/- 0.28
      arbitrary units, n = 3; P < 0.05). We investigated V-H(+)-ATPase translocation
      during a postfeeding alkalosis ("alkaline tide"). Gill samples were taken 24-26 h
      after dogfish were fed to satiety in a natural-like feeding regime. Immunolabeled
      gill sections revealed that V-H(+)-ATPase translocated to the basolateral
      membrane in the postfed fish. Confirming this result, V-H(+)-ATPase abundance was
      twofold higher in gill cell membranes of the postfed fish than in fasted fish (n
      = 4-5; P < 0.05). These results indicate that 1) intracellular H(+) or HCO(3)(-)
      produced by CA (and not blood pH or HCO(3)(-)) is likely the stimulus that
      triggers the V-H(+)-ATPase translocation into the basolateral membrane in
      alkalotic fish and 2) V-H(+)-ATPase translocation is important for enhanced
      HCO(3)(-) secretion during a naturally occurring postfeeding alkalosis.

PMID- 17204589
TI  - Effects of maternal parity and late gestational nutrition on mRNA abundance for
      growth factors in the liver of postnatal sheep.
AB  - The liver is a major metabolic and endocrine organ in growing neonates, but the
      extent to which its hormone receptor (R) sensitivity is potentially determined by
      maternal parity and the mother's nutritional environment is unknown. This was
      therefore investigated by sampling livers from postnatal sheep born to
      nulliparous or multiparous mothers. Offspring were sampled 1 or 30 days after
      birth from mothers consuming either 100 or 50% [i.e., nutrient-restricted (NR)
      group] of total metabolizable energy requirements from 110 days gestation to term
      ( approximately 147 days). Regardless of maternal diet, offspring of nulliparous
      mothers were lighter at birth and had smaller livers. By 1 mo of age, they
      exhibited catch-up growth, an adaptation not seen when mothers were NR, but they
      retained their lighter livers. At both sampling ages, livers from offspring born
      to nulliparous mothers exhibited increased mRNA abundance for growth hormone (GH)
      receptor, IGF-IR, plus hepatocyte growth factor (HGF); and at day 1 only IGF-I,
      but not IGF-IIR mRNA was decreased. In addition, mRNA for IGF-II, the HGFR, c
      Met, and Bax were persistently reduced in these offspring. Effects of parity were
      largely unaffected by maternal nutrient restriction. Maternal parity therefore
      has a substantial effect on liver size during postnatal development and its
      receptor population that is not dependent on maternal diet. First-born offspring
      appear to exhibit a resetting of the endocrine control of hepatic growth within
      the HGF and GH-IGF axis, which could have later consequences after their growth
      has caught up.

PMID- 17204590
TI  - Increased duration of simulated childbirth injuries results in increased time to
      recovery.
AB  - Stress urinary incontinence (SUI) development is strongly correlated with vaginal
      childbirth, particularly increased duration of the second stage of labor.
      However, the mechanisms of pelvic floor injury leading to SUI are largely
      unknown. The aim of this study was to determine the effects of increased duration
      of vaginal distension (VD) on voiding cystometry, leak point pressure testing,
      and histology. Sixty-nine virgin female rats underwent VD with an inflated
      balloon for either 1 or 4 h, while 33 age-matched rats were sham-VD controls.
      Conscious cystometry, leak point pressure testing, and histopathology were
      determined 4 days, 10 days, and 6 wk after VD. The increase in abdominal pressure
      to leakage (LPP) during leak point pressure testing was significantly decreased
      in both distension groups 4 days after distension, indicative of short-term
      decreased urethral resistance. Ten days after VD, LPP was significantly decreased
      in the 4-h but not the 1-h distension group, indicating that a longer recovery
      time is needed after longer distension duration. Six weeks after VD, LPP was not
      significantly different from sham-VD values, indicating a return toward normal
      urethral resistance. In contrast, 6 wk after VD of either duration, the distended
      rats had not undergone the same increase in voided volume as the sham-VD group,
      suggesting that some effects of VD do not resolve within 6 wk. Both VD groups
      demonstrated histopathological evidence of acute injuries and tissue remodeling.
      In conclusion, this experiment suggests pressure-induced hypoxia as a possible
      mechanism of injury in vaginal delivery.

PMID- 17204591
TI  - Intermittent hypobaric hypoxia exposure does not cause sustained alterations in
      autonomic control of blood pressure in young athletes.
AB  - Intermittent hypoxia (IH), which refers to the discontinuous use of hypoxia to
      reproduce some key features of altitude acclimatization, is commonly used in
      athletes to improve their performance. However, variations of IH are also used as
      a model for sleep apnea, causing sustained sympathoexcitation and hypertension in
      animals and, thus, raising concerns over the safety of this model. We tested the
      hypothesis that chronic IH at rest alters autonomic control of arterial pressure
      in healthy trained individuals. Twenty-two young athletes (11 men and 11 women)
      were randomly assigned to hypobaric hypoxia (simulated altitude of 4,000-5,500 m)
      or normoxia (500 m) in a double-blind and placebo-controlled design. Both groups
      rested in a hypobaric chamber for 3 h/day, 5 days/wk for 4 wk. In the sitting
      position, resting hemodynamics, including heart rate (HR), blood pressure (BP),
      cardiac output (Q(c), C(2)H(2) rebreathing), stroke volume (SV = Q(c)/HR), and
      total peripheral resistance (TPR = mean BP/Q(c)), were measured, dynamic
      cardiovascular regulation was assessed by spectral and transfer function analysis
      of cardiovascular variability, and cardiac-vagal baroreflex function was
      evaluated by a Valsalva maneuver, twice before and 3 days after the last chamber
      exposure. We found no significant differences in HR, BP, Q(c), SV, TPR,
      cardiovascular variability, or cardiac-vagal baroreflex function between the
      groups at any time. These results suggest that exposure to intermittent hypobaric
      hypoxia for 4 wk does not cause sustained alterations in autonomic control of BP
      in young athletes. In contrast to animal studies, we found no secondary evidence
      for sustained physiologically significant sympathoexcitation in this model.

PMID- 17204592
TI  - NPY Y1 receptor is involved in ghrelin- and fasting-induced increases in
      foraging, food hoarding, and food intake.
AB  - Fasting triggers a constellation of physiological and behavioral changes,
      including increases in peripherally produced ghrelin and centrally produced
      hypothalamic neuropeptide Y (NPY). Refeeding stimulates food intake in most
      species; however, hamsters primarily increase foraging and food hoarding with
      smaller increases in food intake. Fasting-induced increases in foraging and food
      hoarding in Siberian hamsters are mimicked by peripheral ghrelin, central NPY,
      and NPY Y1 receptor agonist injections. Because fasting stimulates ghrelin and
      subsequently NPY synthesis/release, it may be that fasting-induced increased
      hoarding is mediated by NPY Y1 receptor activation. Therefore, we asked: Can an
      Y1 receptor antagonist block fasting- or ghrelin-induced increases in foraging,
      food hoarding, and food intake? This was accomplished by injecting the NPY Y1
      receptor antagonist 1229U91 intracerebroventricularly in hamsters fasted, fed, or
      given peripheral ghrelin injections and housed in a running wheel-based food
      delivery foraging system coupled with simulated-burrow housing. Three foraging
      conditions were used: 1) no running wheel access, free food, 2) running wheel
      access, free food, or 3) foraging requirement (10 revolutions/pellet) for food.
      Fasting was a more potent stimulator of foraging and food hoarding than ghrelin.
      Concurrent injections of 1229U91 completely blocked fasting- and ghrelin-induced
      increased foraging and food intake and attenuated, but did not always completely
      block, fasting- and ghrelin-induced increases in food hoarding. Collectively,
      these data suggest that the NPY Y1 receptor is important for the effects of
      ghrelin- and fasting-induced increases in foraging and food intake, but other NPY
      receptors and/or other neurochemical systems are involved in increases in food
      hoarding.

PMID- 17204593
TI  - Presystemic influences on thirst, salt appetite, and vasopressin secretion in the
      hypovolemic rat.
AB  - The present studies investigated the influence of presystemic signals on the
      control of thirst, salt appetite, and vasopressin (VP) secretion in rats during
      nonhypotensive hypovolemia. Rats were injected with 30% polyethylene glycol (PEG)
      solution, deprived of food and water overnight, and then allowed to drink water,
      0.15 M NaCl, or 0.30 M NaCl. The PEG treatment, which produced 30-40% plasma
      volume deficits, elicited rapid intakes in an initial bout of drinking, but rats
      consumed much more 0.15 M NaCl than water or 0.30 M NaCl. In considering why
      drinking stopped sooner when water or concentrated saline was ingested, it seemed
      relevant that little or no change in systemic plasma Na(+) concentration was
      observed during the initial bouts and that the partial repair of hypovolemia was
      comparable, regardless of which fluid was consumed. In rats that drank 0.15 M
      NaCl, gastric emptying was fastest and the combined volume of ingested fluid in
      the stomach and small intestine was largest. These and other observations are
      consistent with the hypothesis that fluid ingestion by hypovolemic rats is
      inhibited by distension of the stomach and proximal small intestine and that
      movement of dilute or concentrated fluid into the small intestine provides
      another presystemic signal that inhibits thirst or salt appetite, respectively.
      On the other hand, an early effect of water or saline consumption on VP secretion
      in PEG-treated rats was not observed, in contrast to recent findings in
      dehydrated rats. Thus the controls of fluid ingestion and VP secretion are
      similar but not identical during hypovolemia.

PMID- 17204594
TI  - Soluble guanylyl cyclase expression is reduced in LPS-induced lung injury.
AB  - Soluble guanylyl cyclase (sGC) is a cGMP-generating enzyme implicated in the
      control of smooth muscle tone that also regulates platelet aggregation. Moreover,
      sGC activation has been shown to reduce leukocyte adherence to the endothelium.
      Herein, we investigated the expression of sGC in a murine model of LPS-induced
      lung injury and evaluated the effects of sGC inhibition in the context of acute
      lung injury (ALI). Lung tissue sGC alpha1 and beta1 subunit protein levels were
      determined by Western blot and immunohistochemistry, and steady-state mRNA levels
      for the beta1 subunit were assessed by real-time PCR. LPS inhalation resulted in
      a decrease in beta1 mRNA levels, as well as a reduction in both sGC subunit
      protein levels. Decreased alpha1 and beta1 expression was observed in bronchial
      smooth muscle and epithelial cells. TNF-alpha was required for the LPS-triggered
      reduction in sGC protein levels, as no change in alpha1 and beta1 levels was
      observed in TNF-alpha knockout mice. To determine the effects of sGC blockade in
      LPS-induced lung injury, mice were exposed to 1H-[1,2,4]oxodiazolo[4,3
      a]quinoxalin-l-one (ODQ) prior to the LPS challenge. Such pretreatment led to a
      further increase in total cell number (mainly due to an increase in neutrophils)
      and protein concentration in the bronchoalveoalar lavage fluid; the effects of
      ODQ were reversed by a cell-permeable cGMP analog. We conclude that sGC
      expression is reduced in LPS-induced lung injury, while inhibition of the enzyme
      with ODQ worsens lung inflammation, suggesting that sGC exerts a protective role
      in ALI.

PMID- 17204595
TI  - A defect in glucose-induced dissociation of glucokinase from the regulatory
      protein in Zucker diabetic fatty rats in the early stage of diabetes.
AB  - Effect of stimulation of glucokinase (GK) export from the nucleus by small
      amounts of sorbitol on hepatic glucose flux in response to elevated plasma
      glucose was examined in 6-h fasted Zucker diabetic fatty rats at 10 wk of age.
      Under basal conditions, plasma glucose, insulin, and glucagon were approximately
      8 mM, 2,000 pmol/l, and 60 ng/l, respectively. Endogenous glucose production
      (EGP) was 44 +/- 4 micromol x kg(-1) x min(-1). When plasma glucose was raised to
      approximately 17 mM, GK was still predominantly localized with its inhibitory
      protein in the nucleus. EGP was not suppressed. When sorbitol was infused at 5.6
      and 16.7 micromol x kg(-1) x min(-1), along with the increase in plasma glucose,
      GK was exported to the cytoplasm. EGP (23 +/- 19 and 12 +/- 5 micromol x kg(-1) x
      min(-1)) was suppressed without a decrease in glucose 6-phosphatase flux (145 +/-
      23 and 126 +/- 16 vs. 122 +/- 10 micromol x kg(-1) x min(-1) without sorbitol)
      but increased in glucose phosphorylation as indicated by increases in glucose
      recycling (122 +/- 17 and 114 +/- 19 vs. 71 +/- 11 microl x kg(-1) x min(-1)),
      glucose-6-phosphate content (254 +/- 32 and 260 +/- 35 vs. 188 +/- 20 nmol/g
      liver), fractional contribution of plasma glucose to uridine 5'-diphosphate
      glucose flux (43 +/- 8 and 42 +/- 8 vs. 27 +/- 6%), and glycogen synthesis from
      plasma glucose (20 +/- 4 and 22 +/- 5 vs. 9 +/- 4 mumol glucose/g liver). The
      decreased glucose effectiveness to suppress EGP and stimulate hepatic glucose
      uptake may result from failure of the sugar to activate GK by stimulating the
      translocation of the enzyme.

PMID- 17204596
TI  - Activation of the external urethral sphincter central pattern generator by a 5
      HT(1A) receptor agonist in rats with chronic spinal cord injury.
AB  - We recently demonstrated that treatment with the 5-HT(1A/7) receptor agonist [(R)
      (+)-8-hydroxy-2-di-n-propylamino]tetralin (8-OH-DPAT) increases bladder capacity
      in chloralose-anesthetized female cats with chronic spinal cord injury. In the
      current study, we investigated the effects of 8-OH-DPAT on bladder capacity and
      external urethral sphincter (EUS) activity in urethane-anesthetized female rats
      (initial body mass 175-200 g) with chronic spinal cord injury (transsection at
      T10). Cystometric study took place 8-12 wk posttranssection. Intravesical
      pressure was monitored in urethane-anesthetized rats with a transvesical
      catheter, and EUS activity was assessed electromyographically. Spinal cord injury
      disrupts phasic activity of the EUS, resulting in decreased voiding efficiency
      and increased residual volume. 8-OH-DPAT induced a dose-dependent decrease in
      bladder capacity (the opposite of its effect in chronic spinal cord-injured cats)
      with an increase in micturition volume and decrease in residual volume resulting
      from improvement in voiding efficiency. The unexpected improvement in voiding
      efficiency can be explained by the 8-OH-DPAT-induced emergence of phasic EUS
      relaxation. Phasic EUS relaxation was also altered by 8-OH-DPAT in spinally
      intact rats, whereas the 5-HT(1A) receptor antagonist N-tert-butyl-3-[4-(2
      methoxyphenyl)-piperazin-1-yl]-2-phenylpropanamide (WAY-100635), on its own, was
      without effect. It remains to be determined when phasic relaxation is restored
      after spinal cord injury, and indeed whether it is ever truly lost or is only
      temporarily separated from excitatory input.

PMID- 17204597
TI  - Health care-based interventions for women who have experienced sexual violence: a
      review of the literature.
AB  - Thirty publications that evaluated health care-based interventions for women who
      experienced sexual violence were reviewed. The findings highlight that clinicians
      often need training in the provision sexual assault care, and that not all
      emergency departments have sexual assault care protocols. Studies examining
      effectiveness found that Sexual Assault Nurse Examiner programs are very helpful,
      that health care-based sexual assault treatment settings attract more women than
      do forensic-based settings, that sexual assault survivors often prefer a
      combination of medication and counseling treatment, and that preexam
      administration of a video explaining the collection of forensic evidence may
      reduce women's stress during the procedure. Studies on postexposure HIV
      prophylaxis found that many women did not complete the treatment regimen, often
      because of side effects. Emergency contraception to prevent postrape pregnancy is
      not consistently offered to women. Only one study reported on abortion as part of
      the range of sexual assault services.

PMID- 17204598
TI  - Preventing female-perpetrated sexual abuse.
AB  - Sexual abuse and sexual assault are serious public health concerns. Although
      almost all of the research shows that the majority of sexual perpetrators are
      males, there is growing evidence that female-perpetrated sexual abuse is not rare
      and that the consequences of female-perpetrated sexual abuse can be just as
      traumatic as male-perpetrated sexual abuse. Despite this, there has been very
      little research published that has focused on female sex offending. Furthermore,
      although there have been some efforts in the past decade to stop sexual offenses
      by targeting potential perpetrators, few efforts have specifically focused on
      preventing females from becoming sex offenders. In an attempt to fill this gap,
      this article describes common characteristics of female sex offenders; and, based
      on these characteristics, suggestions are given of possible ways to intervene in
      the lives of at-risk females before they offend.

PMID- 17204599
TI  - Risk factors for victimization in romantic relationships of young women: a review
      of empirical studies and implications for prevention.
AB  - This article reviews the literature on risk factors for victimization in romantic
      relationships of adolescent girls and young adult women. The review includes 61
      empirical studies published between 1986 and 2006 that have investigated risk
      factors for sustained psychological, sexual, and physical violence in romantic
      relationships of young women ages 12 to 24. An ecological approach is used as a
      conceptual model to review risk factors into four categories: sociodemographic
      factors, individual factors (personal and interpersonal), environmental factors
      (family, community, and peers), and contextual factors (linked to the romantic
      relationship). Methodological limitations of the studies in terms of measurement
      issues, samples studied, research designs, and underlying conceptual models are
      discussed. Finally, implications for prevention programming are considered.
      Recommendations are presented about which clientele should be targeted, which
      risk factors should be considered, and when programs should be implemented.

PMID- 17204600
TI  - Vicarious traumatization: the impact on therapists who work with sexual
      offenders.
AB  - This article reviews the descriptive and empirical literature examining vicarious
      traumatization in therapists treating sexual offenders. Vicarious traumatization
      in sexual offender therapists is described, including an examination of the
      relationships between vicarious traumatization and client, therapist, and setting
      and therapy characteristics. Special attention is given to those unique factors
      that contribute to the development of vicarious traumatization in this group, as
      well as consideration of why therapists treating offenders or victims may differ
      in their experience and development of vicarious traumatization. Evidence from
      the research reviewed suggests that sexual offender therapists do experience
      symptoms of vicarious traumatization. Factors most strongly associated with the
      development of vicarious traumatization in sexual offender therapists include
      professional experience, treatment setting, and coping strategies employed by the
      therapists. Implications and recommendations for professionals and policymakers
      are discussed.

PMID- 17204602
TI  - A meta-analysis of human embryonic stem cells transcriptome integrated into a web
      based expression atlas.
AB  - Microarray technology provides a unique opportunity to examine gene expression
      patterns in human embryonic stem cells (hESCs). We performed a meta-analysis of
      38 original studies reporting on the transcriptome of hESCs. We determined that
      1,076 genes were found to be overexpressed in hESCs by at least three studies
      when compared to differentiated cell types, thus composing a "consensus hESC gene
      list." Only one gene was reported by all studies: the homeodomain transcription
      factor POU5F1/OCT3/4. The list comprised other genes critical for pluripotency
      such as the transcription factors NANOG and SOX2, and the growth factors
      TDGF1/CRIPTO and Galanin. We show that CD24 and SEMA6A, two cell surface protein
      coding genes from the top of the consensus hESC gene list, display a strong and
      specific membrane protein expression on hESCs. Moreover, CD24 labeling permits
      the purification by flow cytometry of hESCs cocultured on human fibroblasts. The
      consensus hESC gene list also included the FZD7 WNT receptor, the G protein
      coupled receptor GPR19, and the HELLS helicase, which could play an important
      role in hESCs biology. Conversely, we identified 783 genes downregulated in hESCs
      and reported in at least three studies. This "consensus differentiation gene
      list" included the IL6ST/GP130 LIF receptor. We created an online hESC expression
      atlas, http://amazonia.montp.inserm.fr, to provide an easy access to this public
      transcriptome dataset. Expression histograms comparing hESCs to a broad
      collection of fetal and adult tissues can be retrieved with this web tool for
      more than 15,000 genes.

PMID- 17204604
TI  - Activin a efficiently specifies definitive endoderm from human embryonic stem
      cells only when phosphatidylinositol 3-kinase signaling is suppressed.
AB  - Human ESCs (hESCs) respond to signals that determine their pluripotency,
      proliferation, survival, and differentiation status. In this report, we
      demonstrate that phosphatidylinositol 3-kinase (PI3K) antagonizes the ability of
      hESCs to differentiate in response to transforming growth factor beta family
      members such as Activin A and Nodal. Inhibition of PI3K signaling efficiently
      promotes differentiation of hESCs into mesendoderm and then definitive endoderm
      (DE) by allowing them to be specified by Activin/Nodal signals present in hESC
      cultures. Under conditions where hESCs are grown in mouse embryo fibroblast
      conditioned medium under feeder-free conditions, approximately 70%-80% are
      converted into DE following 5 days of treatment with inhibitors of the PI3K
      pathway, such as LY 294002 and AKT1-II. Microarray and quantitative polymerase
      chain reaction-based gene expression profiling demonstrates that definitive
      endoderm formation under these conditions closely parallels that following
      specification with elevated Activin A and low fetal calf serum (FCS)/knockout
      serum replacement (KSR). Reduced insulin/insulin-like growth factor (IGF)
      signaling was found to be critical for cell fate commitment into DE. Levels of
      insulin/IGF present in FCS/KSR, normally used to promote self-renewal of hESCs,
      antagonized differentiation. In summary, we show that generation of hESC-DE
      requires two conditions: signaling by Activin/Nodal family members and release
      from inhibitory signals generated by PI3K through insulin/IGF. These findings
      have important implications for our understanding of hESC self-renewal and early
      cell fate decisions.

PMID- 17204605
TI  - Multilineage differentiation and characterization of the human fetal osteoblastic
      1.19 cell line: a possible in vitro model of human mesenchymal progenitors.
AB  - The in vitro study of human bone marrow mesenchymal stromal cells (BMMSCs) has
      largely depended on the use of primary cultures. Although these are excellent
      model systems, their scarcity, heterogeneity, and limited lifespan restrict their
      usefulness. This has led researchers to look for other sources of MSCs, and
      recently, such a population of progenitor/stem cells has been found in mesodermal
      tissues, including bone. We therefore hypothesized that a well-studied and
      commercially available clonal human osteoprogenitor cell line, the fetal
      osteoblastic 1.19 cell line (hFOB), may have multilineage differentiation
      potential. We found that undifferentiated hFOB cells possess similar cell surface
      markers as BMMSCs and also express the embryonic stem cell-related pluripotency
      gene, Oct-4, as well as the neural progenitor marker nestin. hFOB cells can also
      undergo multilineage differentiation into the mesodermal lineages of chondrogenic
      and adipocytic cell types in addition to its predetermined pathway, the mature
      osteoblast. Moreover, as with BMMSCs, under neural-inducing conditions, hFOB
      cells acquire a neural-like phenotype. This human cell line has been a widely
      used model of normal osteoblast differentiation. Our data suggest that hFOB cells
      may provide for researchers an easily available, homogeneous, and consistent in
      vitro model for study of human mesenchymal progenitor cells.

PMID- 17204606
TI  - EphB/ephrin-B interaction mediates adult stem cell attachment, spreading, and
      migration: implications for dental tissue repair.
AB  - Human adult dental pulp stem cells (DPSCs) reside predominantly within the
      perivascular niche of dental pulp and are thought to originate from migrating
      neural crest cells during development. The Eph family of receptor tyrosine
      kinases and their ligands, the ephrin molecules, play an essential role in the
      migration of neural crest cells during development and stem cell niche
      maintenance. The present study examined the expression and function of the B
      subclass Eph/ephrin molecules on DPSCs. Multiple receptors were primarily
      identified on DPSCs within the perivascular niche, whereas ephrin-B1 and ephrin
      B3 were expressed by the surrounding pulp tissue. EphB/ephrin-B bidirectional
      signaling inhibited cell attachment and spreading, predominately via the mitogen
      activated protein kinase (MAPK) pathway for forward signaling and phosphorylation
      of Src family tyrosine kinases via reverse ephrin-B signaling. DPSC migration was
      restricted through unidirectional ephrin-B1-activated EphB forward signaling,
      primarily signaling through the MAPK pathway. Furthermore, we observed that
      ephrin-B1 was downregulated in diseased adult teeth compared with paired
      uninjured controls. Collectively, these studies suggest that EphB/ephrin-B
      molecules play a role in restricting DPSC attachment and migration to maintain
      DPSCs within their stem cell niche under steady-state conditions. These results
      may have implications for dental pulp development and regeneration.

PMID- 17204607
TI  - Long-term follow-up of patients with non-Hodgkin lymphoma following myeloablative
      therapy and autologous transplantation of CD34+-selected peripheral blood
      progenitor cells.
AB  - Graft engineering by CD34(+) selection of peripheral blood progenitor cells
      (PBPC) has been used in non-Hodgkin lymphoma (NHL) with the aim to reduce relapse
      related to tumor cells within the graft. From September 1995 to January 2000, 39
      patients with newly diagnosed (n = 31) or relapsed (n = 8) NHL were treated in
      our institution with myeloablative therapy followed by CD34(+) selected
      autologous PBPC transplantation. Thirty-one patients were diagnosed with
      follicular lymphoma, and eight patients with mantle-cell lymphoma. All patients
      had advanced disease (26% of patients stage III and 74% stage IV, Ann Arbor
      classification). Induction therapy resulted in a complete remission in 17
      patients and a partial remission in 22 patients. PBPC were mobilized after
      cytotoxic chemotherapy with granulocyte colony-stimulating factor support.
      CD34(+) selection was performed using immunomagnetic beads (Baxter Isolex 300SA
      or 300i Magnetic Cell Separation System). Most patients (85%) received total body
      irradiation and high-dose cyclophosphamide as myeloablative regimen. Twelve
      patients also received rituximab 375 mg/m(2) before radiation and before the
      start of the cyclophosphamide treatment. The mean CD34(+) cell number for
      transplantation was 6.5 x 10(6) CD34(+) cells/kg of body weight. Platelet
      recovery (>20,000/microl median on day 13) and leukocyte recovery (>1,000/microl
      median on day 12) were within expected range. The estimated median follow-up was
      47 months. The probabilities of freedom from progression, overall survival, and
      event-free survival 4 years after transplantation were 96%, 90%, and 87%,
      respectively, for patients with follicular lymphoma and 42%, 63%, and 33%,
      respectively, for patients with mantle-cell lymphoma. Risk factors for relapse
      were age and extranodal manifestation of disease. The rate of lethal infections
      in the 12-month follow-up period was 8%. We conclude that CD34(+) selection of
      autologous transplants following myeloablative therapy is feasible and results in
      long-term remission in the majority of patients, but the procedure is probably
      related to a higher rate of lethal infections.

PMID- 17204608
TI  - An X chromosome gene, WTX, is commonly inactivated in Wilms tumor.
AB  - Wilms tumor is a pediatric kidney cancer associated with inactivation of the WT1
      tumor-suppressor gene in 5 to 10% of cases. Using a high-resolution screen for
      DNA copy-number alterations in Wilms tumor, we identified somatic deletions
      targeting a previously uncharacterized gene on the X chromosome. This gene, which
      we call WTX, is inactivated in approximately one-third of Wilms tumors (15 of 51
      tumors). Tumors with mutations in WTX lack WT1 mutations, and both genes share a
      restricted temporal and spatial expression pattern in normal renal precursors. In
      contrast to biallelic inactivation of autosomal tumor-suppressor genes, WTX is
      inactivated by a monoallelic "single-hit" event targeting the single X chromosome
      in tumors from males and the active X chromosome in tumors from females.

PMID- 17204609
TI  - Direct measurements of the convective recycling of the upper troposphere.
AB  - We present a statistical representation of the aggregate effects of deep
      convection on the chemistry and dynamics of the upper troposphere (UT) based on
      direct aircraft observations of the chemical composition of the UT over the
      eastern United States and Canada during summer. These measurements provide unique
      observational constraints on the chemistry occurring downwind of convection and
      the rate at which air in the UT is recycled. These results provide quantitative
      measures that can be used to evaluate global climate and chemistry models.

PMID- 17204610
TI  - Coding/decoding and reversibility of droplet trains in microfluidic networks.
AB  - Droplets of one liquid suspended in a second, immiscible liquid move through a
      microfluidic device in which a channel splits into two branches that reconnect
      downstream. The droplets choose a path based on the number of droplets that
      occupy each branch. The interaction among droplets in the channels results in
      complex sequences of path selection. The linearity of the flow through the
      microchannels, however, ensures that the behavior of the system can be reversed.
      This reversibility makes it possible to encrypt and decrypt signals coded in the
      intervals between droplets. The encoding/decoding device is a functional
      microfluidic system that requires droplets to navigate a network in a precise
      manner without the use of valves, switches, or other means of external control.

PMID- 17204611
TI  - A New Year.

PMID- 17204612
TI  - 2007 U.S. budget. NSF braces for opportunities lost.

PMID- 17204613
TI  - Endangered species. U.S. weighs protection for polar bears.

PMID- 17204614
TI  - Scientific misconduct. Japan's universities take action.

PMID- 17204615
TI  - Biomedical policy. New autism law focuses on patients, environment.

PMID- 17204616
TI  - Bart Gordon profile. New chair of House science panel takes extreme route to
      moderation.

PMID- 17204617
TI  - Epidemiology. Indonesia taps village wisdom to fight bird flu.

PMID- 17204618
TI  - Epidemiology. Human cases create challenges and puzzles.

PMID- 17204620
TI  - Fall meeting of the American Geophysical Union. Could mother nature give the
      warming Arctic a reprieve?

PMID- 17204619
TI  - Biomedicine. Puzzling out the pains in the gut.

PMID- 17204621
TI  - Fall meeting of the American Geophysical Union. Weather forecasting way out
      there.

PMID- 17204622
TI  - Fall meeting of the American Geophysical Union. Snapshots from the meeting.

PMID- 17204623
TI  - Fall meeting of the American Geophysical Union. The earthquake that will eat
      Tokyo.

PMID- 17204624
TI  - The Israeli-Palestinian Science Organization.

PMID- 17204625
TI  - Another nail in which coffin?

PMID- 17204626
TI  - Chemistry Nobel rich in structure.

PMID- 17204628
TI  - Sustainability. Anchovy fishery threat to Patagonian ecosystem.

PMID- 17204629
TI  - Molecular biology. Do Watson and Crick motor from X to Z?

PMID- 17204630
TI  - Physics. Negative refractive index at optical wavelengths.

PMID- 17204631
TI  - Ecology. The heartbreak of adapting to global warming.

PMID- 17204632
TI  - Atmosphere. Aerosols before pollution.

PMID- 17204633
TI  - Plant science. Nodules and hormones.

PMID- 17204636
TI  - Stalking discovery from the infinitesimal to the infinite.

PMID- 17204634
TI  - Ecology. Rangeland ecology in a changing world.

PMID- 17204637
TI  - Quarks and the cosmos.
AB  - Cosmology is in the midst of a period of revolutionary discovery, propelled by
      bold ideas from particle physics and by technological advances from gigapixel
      charge-coupled device cameras to peta-scale computing. The basic features of the
      universe have now been determined: It is 13.7 billion years old, spatially flat,
      and expanding at an accelerating rate; it is composed of atoms (4%), exotic dark
      matter (20%), and dark energy (76%); and there is evidence that galaxies and
      other structures were seeded by quantum fluctuations. Although we know much about
      the universe, we understand far less. Poised to dramatically advance our
      understanding of both the universe and the laws that govern it, cosmology is on
      the verge of a golden age.

PMID- 17204638
TI  - Particle dark matter in the universe: at the brink of discovery?
AB  - The nature of dark matter is one of the central problems of cosmology, particle
      physics, and gravity. It may be made of still unknown particles produced in the
      early universe. Much progress has been made in attempts to detect these particles
      and in the development of the required experimental techniques. Results from
      direct searches, the Large Hadron Collider, and the Gamma-ray Large Area Space
      Telescope offer promising opportunities within the next decade to find the
      missing dark matter.

PMID- 17204639
TI  - Neutrino astrophysics: a new tool for exploring the universe.
AB  - In the past four decades a new type of astronomy has emerged, where instead of
      looking up into the sky, "telescopes" are buried miles underground or deep under
      water or ice and search not for photons (that is, light), but rather for
      particles called neutrinos. Neutrinos are nearly massless particles that interact
      very weakly with matter. The detection of neutrinos emitted by the Sun and by a
      nearby supernova provided direct tests of the theory of stellar evolution and led
      to modifications of the standard model describing the properties of elementary
      particles. At present, several very large neutrino detectors are being
      constructed, aiming at the detection of the most powerful sources of energy and
      particles in the universe. The hope is that the detection of neutrinos from these
      sources, which are extra-Galactic and are most likely powered by mass accretion
      onto black holes, will not only allow study of the sources, but, much like solar
      neutrinos, will also provide new information about fundamental properties of
      matter.

PMID- 17204640
TI  - Neutrino astrophysics experiments beneath the sea and ice.
AB  - Neutrino astronomy beyond the Sun was first imagined in the late 1950s. A
      neutrino detector at the bottom of Lake Baikal, the deployment of detectors in
      the Mediterranean Sea, and the construction of a kilometer-scale neutrino
      telescope at the South Pole exemplify current efforts to realize this dream.

PMID- 17204641
TI  - Cosmic rays: the highest-energy messengers.
AB  - The origin of the most energetic particles ever observed, cosmic rays, will begin
      to be revealed in the next few years. Newly constructed ultrahigh-energy cosmic
      ray observatories together with high-energy gamma-ray and neutrino observatories
      are well positioned to unveil this mystery before the centenary of their
      discovery in 2012. Cosmic ray sources are likely to involve the most energetic
      phenomena ever witnessed in the universe.

PMID- 17204642
TI  - The very-high-energy gamma-ray sky.
AB  - Over the past few years, very-high-energy gamma-ray astronomy has emerged as a
      truly observational discipline, with many detected sources representing different
      galactic and extragalactic source populations-supernova remnants, pulsar wind
      nebulae, giant molecular clouds, star formation regions, compact binary systems,
      and active galactic nuclei. It is expected that observations with the next
      generation of stereoscopic arrays of imaging atmospheric Cherenkov telescopes
      over a very broad energy range from 10(10) to 10(15) electron volts will
      dramatically increase the number of very-high-energy gamma-ray sources, thus
      having a huge impact on the development of astrophysics, cosmology, and particle
      astrophysics.

PMID- 17204643
TI  - Cross-species identification of Mendel's I locus.
AB  - A key gene involved in plant senescence, mutations of which partially disable
      chlorophyll catabolism and confer stay-green leaf and cotyledon phenotypes, has
      been identified in Pisum sativum, Arabidopsis thaliana, and Festuca pratensis by
      using classical and molecular genetics and comparative genomics. A stay-green
      locus in F. pratensis is syntenically equivalent to a similar stay-green locus on
      rice chromosome 9. Functional testing in Arabidopsis of a homolog of the rice
      candidate gene revealed (i) senescence-associated gene expression and (ii) a stay
      green phenotype after RNA interference silencing. Genetic mapping in pea
      demonstrated cosegregation with the yellow/green cotyledon polymorphism (I/i)
      first reported by Gregor Mendel in 1866.

PMID- 17204644
TI  - Atom interferometer measurement of the newtonian constant of gravity.
AB  - We measured the Newtonian constant of gravity, G, using a gravity gradiometer
      based on atom interferometry. The gradiometer measures the differential
      acceleration of two samples of laser-cooled Cs atoms. The change in gravitational
      field along one dimension is measured when a well-characterized Pb mass is
      displaced. Here, we report a value of G = 6.693 x 10(-11) cubic meters per
      kilogram second squared, with a standard error of the mean of +/-0.027 x 10(-11)
      and a systematic error of +/-0.021 x 10(-11) cubic meters per kilogram second
      squared. The possibility that unknown systematic errors still exist in
      traditional measurements makes it important to measure G with independent
      methods.

PMID- 17204645
TI  - Conductance-controlled point functionalization of single-walled carbon nanotubes.
AB  - We used covalent attachments to single-walled carbon nanotubes (SWNTs) to
      fabricate single-molecule electronic devices. The technique does not rely on
      submicrometer lithography or precision mechanical manipulation, but instead uses
      circuit conductance to monitor and control covalent attachment to an electrically
      connected SWNT. Discrete changes in the circuit conductance revealed chemical
      processes happening in real time and allowed the SWNT sidewalls to be
      deterministically broken, reformed, and conjugated to target species. By
      controlling the chemistry through electronically controlled electrochemical
      potentials, we were able to achieve single chemical attachments. We routinely
      functionalized pristine, defect-free SWNTs at one, two, or more sites and
      demonstrated three-terminal devices in which a single attachment controls the
      electronic response.

PMID- 17204646
TI  - Counting low-copy number proteins in a single cell.
AB  - We have designed a microfluidic device in which we can manipulate, lyse, label,
      separate, and quantify the protein contents of a single cell using single
      molecule fluorescence counting. Generic labeling of proteins is achieved through
      fluorescent-antibody binding. The use of cylindrical optics enables high
      efficiency (approximately 60%) counting of molecules in micrometer-sized
      channels. We used this microfluidic device to quantify beta2 adrenergic receptors
      expressed in insect cells (SF9). We also analyzed phycobiliprotein contents in
      individual cyanobacterial cells (Synechococcus sp. PCC 7942) and observed marked
      differences in the levels of specific complexes in cell populations that were
      grown under nitrogen-depleted conditions.

PMID- 17204647
TI  - Mass-independent sulfur isotopic compositions in stratospheric volcanic
      eruptions.
AB  - The observed mass-independent sulfur isotopic composition (Delta33S) of volcanic
      sulfate from the Agung (March 1963) and Pinatubo (June 1991) eruptions recorded
      in the Antarctic snow provides a mechanism for documenting stratospheric events.
      The sign of Delta33S changes over time from an initial positive component to a
      negative value. Delta33S is created during photochemical oxidation of sulfur
      dioxide to sulfuric acid on a monthly time scale, which indicates a fast process.
      The reproducibility of the results reveals that Delta33S is a reliable tracer to
      chemically identify atmospheric processes involved during stratospheric
      volcanism.

PMID- 17204648
TI  - CO2-forced climate and vegetation instability during Late Paleozoic deglaciation.
AB  - The late Paleozoic deglaciation is the vegetated Earth's only recorded icehouse
      to-greenhouse transition, yet the climate dynamics remain enigmatic. By using the
      stable isotopic compositions of soil-formed minerals, fossil-plant matter, and
      shallow-water brachiopods, we estimated atmospheric partial pressure of carbon
      dioxide (pCO2) and tropical marine surface temperatures during this climate
      transition. Comparison to southern Gondwanan glacial records documents covariance
      between inferred shifts in pCO2, temperature, and ice volume consistent with
      greenhouse gas forcing of climate. Major restructuring of paleotropical flora in
      western Euramerica occurred in step with climate and pCO2 shifts, illustrating
      the biotic impact associated with past CO2-forced turnover to a permanent ice
      free world.

PMID- 17204649
TI  - Climate change affects marine fishes through the oxygen limitation of thermal
      tolerance.
AB  - A cause-and-effect understanding of climate influences on ecosystems requires
      evaluation of thermal limits of member species and of their ability to cope with
      changing temperatures. Laboratory data available for marine fish and
      invertebrates from various climatic regions led to the hypothesis that, as a
      unifying principle, a mismatch between the demand for oxygen and the capacity of
      oxygen supply to tissues is the first mechanism to restrict whole-animal
      tolerance to thermal extremes. We show in the eelpout, Zoarces viviparus, a
      bioindicator fish species for environmental monitoring from North and Baltic Seas
      (Helcom), that thermally limited oxygen delivery closely matches environmental
      temperatures beyond which growth performance and abundance decrease. Decrements
      in aerobic performance in warming seas will thus be the first process to cause
      extinction or relocation to cooler waters.

PMID- 17204650
TI  - A hexanucleotide element directs microRNA nuclear import.
AB  - MicroRNAs (miRNAs) negatively regulate partially complementary target messenger
      RNAs. Target selection in animals is dictated primarily by sequences at the miRNA
      5' end. We demonstrated that despite their small size, specific miRNAs contain
      additional sequence elements that control their posttranscriptional behavior,
      including their subcellular localization. We showed that human miR-29b, in
      contrast to other studied animal miRNAs, is predominantly localized to the
      nucleus. The distinctive hexanucleotide terminal motif of miR-29b acts as a
      transferable nuclear localization element that directs nuclear enrichment of
      miRNAs or small interfering RNAs to which it is attached. Our results indicate
      that miRNAs sharing common 5' sequences, considered to be largely redundant,
      might have distinct functions because of the influence of cis-acting regulatory
      motifs.

PMID- 17204651
TI  - Left-right dynein motor implicated in selective chromatid segregation in mouse
      cells.
AB  - During cell division, copies of mouse chromosome 7 are segregated selectively or
      randomly to daughter cells depending on the cell type. The mechanism for
      differential segregation is unknown. Because mouse left-right dynein (LRD) gene
      mutations result in randomization of visceral organs' laterality, we hypothesized
      that LRD may also function in selective chromatid segregation. Indeed, upon knock
      down by RNA interference methods, LRD depletion disrupts biased segregation. LRD
      messenger RNA presence or absence correlates with the observed segregation
      patterns. This work supports the claim that LRD functions in a mechanism for
      selective chromatid segregation.

PMID- 17204652
TI  - Differential antigen processing by dendritic cell subsets in vivo.
AB  - Dendritic cells (DCs) process and present self and foreign antigens to induce
      tolerance or immunity. In vitro models suggest that induction of immunity is
      controlled by regulating the presentation of antigen, but little is known about
      how DCs control antigen presentation in vivo. To examine antigen processing and
      presentation in vivo, we specifically targeted antigens to two major subsets of
      DCs by using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the
      cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen,
      are specialized for presentation on major histocompatibility complex (MHC) class
      II. This difference in antigen processing is intrinsic to the DC subsets and is
      associated with increased expression of proteins involved in MHC processing.

PMID- 17204653
TI  - Differential transmission of actin motion within focal adhesions.
AB  - Cell migration requires the transmission of motion generated in the actin
      cytoskeleton to the extracellular environment through a complex assembly of
      proteins in focal adhesions. We developed correlational fluorescent speckle
      microscopy to measure the coupling of focal-adhesion proteins to actin filaments.
      Different classes of focal-adhesion structural and regulatory molecules exhibited
      varying degrees of correlated motions with actin filaments, indicating
      hierarchical transmission of actin motion through focal adhesions. Interactions
      between vinculin, talin, and actin filaments appear to constitute a slippage
      interface between the cytoskeleton and integrins, generating a molecular clutch
      that is regulated during the morphodynamic transitions of cell migration.

PMID- 17204654
TI  - Live-cell imaging of enzyme-substrate interaction reveals spatial regulation of
      PTP1B.
AB  - Endoplasmic reticulum-localized protein-tyrosine phosphatase PTP1B terminates
      growth factor signal transduction by dephosphorylation of receptor tyrosine
      kinases (RTKs). But how PTP1B allows for RTK signaling in the cytoplasm is
      unclear. In order to test whether PTP1B activity is spatially regulated, we
      developed a method based on Forster resonant energy transfer for imaging enzyme
      substrate (ES) intermediates in live cells. We observed the establishment of a
      steady-state ES gradient across the cell. This gradient exhibited robustness to
      cell-to-cell variability, growth factor activation, and RTK localization, which
      demonstrated spatial regulation of PTP1B activity. Such regulation may be
      important for generating distinct cellular environments that permit RTK signal
      transduction and that mediate its eventual termination.

PMID- 17204655
TI  - Central command regulation of circulatory function mediated by descending pontine
      cholinergic inputs to sympathoexcitatory rostral ventrolateral medulla neurons.
AB  - Central command is a feedforward neural mechanism that evokes parallel
      modifications of motor and cardiovascular function during arousal and exercise.
      The neural circuitry involved has not been elucidated. We have identified a
      cholinergic neural circuit that, when activated, mimics effects on tonic and
      reflex control of circulation similar to those evoked at the onset of and during
      exercise. Central muscarinic cholinergic receptor (mAChR) activation increased
      splanchnic sympathetic nerve activity (SNA) as well as the range and gain of the
      sympathetic baroreflex via activation of mAChR in the rostral ventrolateral
      medulla (RVLM) in anesthetized artificially ventilated Sprague-Dawley rats. RVLM
      mAChR activation also attenuated and inhibited the peripheral chemoreflex and
      somatosympathetic reflex, respectively. Cholinergic terminals made close
      appositions with a subpopulation of sympathoexcitatory RVLM neurons containing
      either preproenkephalin mRNA or tyrosine hydroxylase immunoreactivity. M2 and M3
      receptor mRNA was present postsynaptically in only non-tyrosine hydroxylase
      neurons. Cholinergic inputs to the RVLM arise only from the pedunculopontine
      tegmental nucleus. Chemical activation of this region produced increases in
      muscle activity, SNA, and blood pressure and enhanced the SNA baroreflex; the
      latter effect was attenuated by mAChR blockade. These findings indicate a novel
      role for cholinergic input from the pedunculopontine tegmental nucleus to the
      RVLM in central cardiovascular command. This pathway is likely to be important
      during exercise where a centrally evoked facilitation of baroreflex control of
      the circulation is required to maintain blood flow to active muscle.

PMID- 17204656
TI  - Myocyte nitroso-redox imbalance in sepsis: NO simple answer.

PMID- 17204657
TI  - The cardiac sarcoplasmic reticulum: filled with Ca2+ and surprises.

PMID- 17204658
TI  - Shooting the messenger: oxidative stress regulates sphingosine-1-phosphate.

PMID- 17204659
TI  - Myosin phosphatase regulatory pathways: different functions or redundant
      functions?

PMID- 17204660
TI  - A novel application for murine double minute 2 antagonists: the p53 tumor
      suppressor network also controls angiogenesis.

PMID- 17204661
TI  - Vascular cell senescence: contribution to atherosclerosis.
AB  - Cardiologists and most physicians believe that aging is an independent risk
      factor for human atherosclerosis, whereas atherosclerosis is thought to be a
      characteristic feature of aging in humans by many gerontologists. Because
      atherosclerosis is among the age-associated changes that almost always escape the
      influence of natural selection in humans, it might be reasonable to regard
      atherosclerosis as a feature of aging. Accordingly, when we investigate the
      pathogenesis of human atherosclerosis, it may be more important to answer the
      question of how we age than what specifically promotes atherosclerosis. Recently,
      genetic analyses using various animal models have identified molecules that are
      crucial for aging. These include components of the DNA-repair system, the tumor
      suppressor pathway, the telomere maintenance system, the insulin/Akt pathway, and
      other metabolic pathways. Interestingly, most of the molecules that influence the
      phenotypic changes of aging also regulate cellular senescence, suggesting a
      causative link between cellular senescence and aging. For example, DNA-repair
      defects can cause phenotypic changes that resemble premature aging, and senescent
      cells that show DNA damage accumulate in the elderly. Excessive calorie intake
      can cause diabetes and hyperinsulinemia, whereas dysregulation of the insulin
      pathway has been shown to induce cellular senescence in vitro. Calorie
      restriction or a reduction of insulin signals extends the lifespan of various
      species and decreases biomarkers of cellular senescence in vivo. There is
      emerging evidence that cellular senescence contributes to the pathogenesis of
      human atherosclerosis. Senescent vascular cells accumulate in human atheroma
      tissues and exhibit various features of dysfunction. In this review, we examine
      the hypothesis that cellular senescence might contribute to atherosclerosis,
      which is a characteristic of aging in humans.

PMID- 17204662
TI  - Platelets as immune cells: bridging inflammation and cardiovascular disease.
AB  - Beyond an eminent role in hemostasis and thrombosis, platelets are characterized
      by expert functions in assisting and modulating inflammatory reactions and immune
      responses. This is achieved by the regulated expression of adhesive and immune
      receptors on the platelet surface and by the release of a multitude of secretory
      products including inflammatory mediators and cytokines, which can mediate the
      interaction with leukocytes and enhance their recruitment. In addition, platelets
      are characterized by an enormous surface area and open canalicular system, which
      in concert with specialized recognition receptors may contribute to the
      engulfment of serum components, antigens, and pathogens. Platelet-dependent
      increases in leukocyte adhesion may not only account for an exacerbation of
      atherosclerosis, for arterial repair processes, but also for lymphocyte
      trafficking during adaptive immunity and host defense. This review compiles a
      selection of platelet-derived tools for bridging inflammation and vascular
      disease and highlights the molecular key components governing platelet-mediated
      mechanisms operative in immune surveillance, vascular remodeling, and
      atherosclerosis.

PMID- 17204663
TI  - A variant of recombinant factor VIIa with enhanced procoagulant and
      antifibrinolytic activities in an in vitro model of hemophilia.
AB  - OBJECTIVE: Recombinant factor VIIa (rFVIIa, NovoSeven) has proven efficacy in
      treating bleeding in hemophilia patients with inhibitors. A rFVIIa analog with
      mutations V158D/E296V/M298Q (NN1731) exhibits increased procoagulant activity in
      in vitro and in vivo models. The aim of this work was to define the effects of
      NN1731 toward factor X activation, platelet activation, thrombin generation, and
      fibrin clot formation and stability. METHODS AND RESULTS: In a cell-based in
      vitro model of hemophilia, rFVIIa and NN1731 similarly increased factor X
      activation on tissue factor-bearing cells; however, NN1731 exhibited 30-fold
      higher factor Xa generation on platelets than similar rFVIIa concentrations.
      NN1731-mediated thrombin generation depended on platelet activation, but NN1731
      did not directly activate platelets. NN1731 produced 4- to 10-fold higher maximal
      thrombin generation rates than equal rFVIIa concentrations. Both rFVIIa and
      NN1731 shortened clotting times in the absence of factors IX and VIII; however,
      NN1731 did so at 50-fold lower concentrations than were required of rFVIIa. In
      fibrinolytic conditions, both rFVIIa and NN1731 increased fibrin formation and
      stability; however, NN1731 was effective at 50-fold lower concentrations than
      were required of rFVIIa. CONCLUSIONS: By increasing factor Xa generation, NN1731
      promotes the formation of thrombin and a stable clot to a greater degree than
      rFVIIa.

PMID- 17204664
TI  - Stem cell factor attenuates vascular smooth muscle apoptosis and increases
      intimal hyperplasia after vascular injury.
AB  - OBJECTIVE: Stem cell factor (SCF) through its cognate receptor, the tyrosine
      kinase c-kit, promotes survival and biological functions of hematopoietic stem
      cells and progenitors. However, whether SCF/c-kit interactions exacerbate intimal
      hyperplasia through attenuating VSMC apoptosis induced by vascular injury has not
      been thoroughly investigated. METHODS AND RESULTS: VSMCs were stimulated with
      serum deprivation and H2O2 to induce apoptosis. The transcription of c-kit mRNA
      and the expression of the c-kit protein by VSMCs were estimated by Q-polymerase
      chain reaction and Western blotting, respectively. The interactions of SCF and c
      kit were investigated by in vitro and in vivo experiments. In vitro, H2O2
      stimulation significantly induced apoptosis of VSMCs as evidenced by the 3- and
      3.2-fold increases of cleaved caspase-3 compared with those in the control group
      by Western blot and flow cytometric analyses, respectively (P<0.01). Stimulation
      of apoptosis also caused 3.5- and 9-fold increases in c-kit mRNA transcription
      and protein expression, respectively, by VSMCs compared with those in the control
      group. Administration of SCF (10 to 1000 ng/mL) significantly lowered the amount
      of cleaved caspase-3 in H2O2-treated VSMCs (P<0.01). Specifically, SCF exerted
      this effect through activating Akt, followed by increasing Bcl-2 and then
      inhibiting the release of cytochrome-c from the mitochondria to the cytosol. In
      vivo, the mouse femoral artery was injured with a wire in SCF mutant (Sl/Sl(d)),
      c-kit mutant (W/W(v)), and colony control mice. In colony control mice, confocal
      microscopy demonstrated that the wire-injury generated a remarkable activation of
      caspase-3 on medial VSMCs, coinciding with upregulation of c-kit expression. The
      wire-injury also caused an increase in the expression of SCF on surviving medial
      VSMCs and cells in the adventitia. The upregulated c-kit expression in the vessel
      wall also facilitated homing by circulating SCF+ cells. Compared with colony
      control mice, vascular injury in SCF mutant and c-kit mutant mice caused a higher
      number of apoptotic VSMCs on day 14 and a lower number of proliferating cells,
      and resulted in significantly less neointimal formation (P<0.01) on day 28.
      CONCLUSIONS: The interactions between SCF and the c-kit receptor play an
      important role in protecting VSMCs against apoptosis and in maintaining intimal
      hyperplasia after vascular injury.

PMID- 17204665
TI  - Total body ABCG1 expression protects against early atherosclerotic lesion
      development in mice.
AB  - OBJECTIVE: ABCG1 has recently been identified as a facilitator of cholesterol and
      phospholipid efflux from macrophages to HDL. In bone marrow transplantation
      studies, we and others have now shown that the absence of macrophage ABCG1 may
      differentially influence atherosclerotic lesions dependent on the experimental
      setting and/or the stage of atherosclerotic lesion development. To further define
      the role of ABCG1 in atherogenesis, we investigated in the current study the
      effect of total body deficiency of ABCG1 on atherosclerotic lesion development.
      METHODS AND RESULTS: ABCG1-/- mice and wild-type littermates were fed an
      atherogenic diet for 12 weeks to induce atherosclerotic lesion formation. Both
      before and after the start of the atherogenic diet, serum lipid levels and
      lipoprotein profiles did not differ significantly between the two groups. In
      addition no significant difference in serum apoE levels was found after diet
      feeding. In wild-type mice the atherogenic diet induced the formation of
      macrophage-rich early lesions (size: 24+/-7x10(3) microm2 [n=6]). Feeding ABCG1-/
      mice the atherogenic diet led to a significant 1.9-fold stimulation of
      atherosclerotic lesion size (46+/-6x10(3) microm2 [n=7]; Student t test P=0.034
      and Mann-Whitney test P=0.050) compared with controls, suggesting a clear
      antiatherogenic role for ABCG1. At the same time, excessive lipid accumulation
      was observed in macrophage-rich areas of the lungs and spleens of ABCG1-/- mice
      as compared with wild-type mice. CONCLUSIONS: Total body ABCG1 expression
      protects against early atherosclerotic lesion development.

PMID- 17204666
TI  - Increased in-stent stenosis in ApoE knockout mice: insights from a novel mouse
      model of balloon angioplasty and stenting.
AB  - OBJECTIVE: We aimed to develop and validate a model of angioplasty and stenting
      in mice that would allow investigation of the response to stent injury using
      genetically modified mouse strains. METHODS AND RESULTS: Aortic segments from
      either C57BL/6 wild-type or atherosclerotic ApoE-KO mice underwent balloon
      angioplasty alone or balloon angioplasty and stenting with a 1.25x2.5 mm
      stainless steel stent. Vessels were carotid-interposition grafted into
      genetically identical littermate recipients and harvested at 1, 7, 14, or 28
      days. In wild-type mice, stenting generated an inflammatory vascular injury
      response between days 1 to 7, leading to the development of neointimal
      hyperplasia by day 14, which further increased in area by day 28 leading to the
      development of in-stent stenosis. Uninjured vessels and vessels injured by
      balloon angioplasty alone developed minimal neointimal hyperplasia. In stented
      ApoE-KO mice, neointimal area at 28 days was 30% greater compared with wild-type
      mice. CONCLUSIONS: By reproducing important features of human stenting in
      atherosclerotic mice, we provide the potential to investigate molecular pathways
      and evaluate novel therapeutic targets for stent injury and restenosis.

PMID- 17204667
TI  - Group v secretory phospholipase A2 promotes atherosclerosis: evidence from
      genetically altered mice.
AB  - OBJECTIVE: Group V secretory phospholipase A2 (GV sPLA2) has been detected in
      both human and mouse atherosclerotic lesions. This enzyme has potent hydrolytic
      activity towards phosphatidylcholine-containing substrates, including lipoprotein
      particles. Numerous studies in vitro indicate that hydrolysis of high density
      lipoproteins (HDL) and low density lipoproteins (LDL) by GV sPLA2 leads to the
      formation of atherogenic particles and potentially proinflammatory lipid
      mediators. However, there is no direct evidence that this enzyme promotes
      atherogenic processes in vivo. METHODS AND RESULTS: We performed gain-of-function
      and loss-of-function studies to investigate the role of GV sPLA2 in atherogenesis
      in LDL receptor-deficient mice. Compared with control mice, animals
      overexpressing GV sPLA2 by retrovirus-mediated gene transfer had a 2.7 fold
      increase in lesion area in the ascending region of the aortic root. Increased
      atherosclerosis was associated with an increase in lesional collagen deposition
      in the same region. Mice deficient in bone marrow-derived GV sPLA2 had a 36%
      reduction in atherosclerosis in the aortic arch/thoracic aorta. CONCLUSIONS: Our
      data in mouse models provide the first in vivo evidence that GV sPLA2 contributes
      to atherosclerotic processes, and draw attention to this enzyme as an attractive
      target for the treatment of atherosclerotic disease.

PMID- 17204668
TI  - Recommendations from the STAIR V meeting on acute stroke trials, technology and
      outcomes.

PMID- 17204670
TI  - Critical care and emergency medicine.

PMID- 17204671
TI  - Recent advances in stroke rehabilitation 2006.

PMID- 17204672
TI  - Health policy and outcomes 2006.

PMID- 17204673
TI  - Advances in imaging 2006.

PMID- 17204674
TI  - Advances in emerging therapies 2006.

PMID- 17204675
TI  - Primary prevention and health services delivery.

PMID- 17204676
TI  - Advances in interventional neuroradiology 2006.

PMID- 17204677
TI  - Advances in vascular cognitive impairment 2006.

PMID- 17204678
TI  - Update on the genetics of stroke and cerebrovascular disease 2006.

PMID- 17204679
TI  - Epsilon PKC may contribute to the protective effect of hypothermia in a rat focal
      cerebral ischemia model.
AB  - BACKGROUND AND PURPOSE: Protein kinase C epsilon (epsilonPKC) has been implicated
      as a neuroprotectant in vitro. We studied epsilonPKC activation (by its
      localization and proteolysis) in a rodent stroke model and correlated the effects
      of hypothermia with epsilonPKC activity after cerebral ischemia. METHODS: Rats
      were subjected to permanent distal middle cerebral artery occlusion plus 1 hour
      of bilateral common carotid artery occlusion. Body temperatures were maintained
      at 37 degrees C or 30 degrees C during common carotid artery occlusion. Brains
      were harvested at 10 minutes, 4 hours, and 24 hours after common carotid artery
      release, and the cortex corresponding to the ischemic core and penumbra was
      dissected. epsilonPKC localization after stroke was assessed by Western blot and
      immunofluorescence microscopy. A caspase-3 inhibitor was used to test whether
      epsilonPKC cleavage is caspase dependent. RESULTS: epsilonPKC in the membrane
      fraction and whole-protein homogenates decreased moderately in the penumbra but
      decreased markedly in the ischemic core. Hypothermia blocked this decrease in
      both the ischemic core and penumbra. Confocal microscopy confirmed that neuronal
      epsilonPKC expression decreased in the ischemic core at 4 hours after
      reperfusion, and this loss was prevented by hypothermia. Two carboxyl-terminal
      cleavage products of epsilonPKC with molecular masses of 43 and 35 kDa were
      detected. Although the protein band of 43 kDa decreased after stroke, the 35-kDa
      band increased. Such changes were not dependent on caspase-3. However,
      hypothermia blocked changes in the cleavage form of 35 kDa but not 43 kDa after
      stroke. CONCLUSIONS: Moderate hypothermia preserves epsilonPKC activity after
      stroke.

PMID- 17204680
TI  - Effects of locomotion training with assistance of a robot-driven gait orthosis in
      hemiparetic patients after stroke: a randomized controlled pilot study.
AB  - BACKGROUND AND PURPOSE: The success of gait rehabilitation after stroke depends
      on active walking exercises. However, the disabling after-effects of stroke often
      make such exercises impossible at the onset of therapy. To facilitate treadmill
      training of paraparetic patients, a robot-driven gait orthosis (Lokomat) was
      developed. We investigated the effects of the Lokomat when used with hemiparetic
      patients. METHODS: The authors conducted a randomized, controlled pilot study of
      30 acute stroke survivors. The treatment group received 30 minutes of robotic
      training daily and the control group 30 minutes of conventional physiotherapy
      daily in addition to 30 minutes of conventional physiotherapy for each group.
      Outcome measures were independence of gait, gait speed, gait parameters, and body
      tissue composition. RESULTS: After 4 weeks of therapy, the walking ability of the
      Lokomat group and the control group expressed as the functional ambulation
      classification was significantly improved. The functional ambulation category
      (median+/- interquartile range) was at baseline 0+/-0 in control and 0+/-1 in the
      therapy group and increased after therapy to 1+/-3 in both groups significantly
      (P=0.01). There was no significant difference in gain of these parameters between
      the groups. The Lokomat group had a significantly longer single stance phase
      (sec; mean+/-SEM) on the paretic leg when walking on the floor. At baseline, it
      was 0.19+/-0.17 and after therapy 0.49+/-0.07 (P=0.014). The control group had
      increased their body weight approximately 1.33+/-1.40 kg (mean+/-SEM; P=0.046),
      mostly as fat mass, whereas the Lokomat group had lost fat mass approximately 
      2.9+/-1.0 kg (mean+/-SEM; P=0.016) and increased their muscle mass approximately
      3.36+/-1.4 kg (mean+/- SEM; P=0.031). CONCLUSIONS: This pilot study indicates
      that Lokomat therapy is a promising intervention for gait rehabilitation.
      Although there was no difference between groups in gain of functional scores, the
      Lokomat group showed an advantage of robotic training over conventional
      physiotherapy in improvement of gait abnormality and body tissue composition.

PMID- 17204681
TI  - Efficacy and safety of anticoagulant treatment in acute cardioembolic stroke: a
      meta-analysis of randomized controlled trials.
AB  - BACKGROUND AND PURPOSE: The role of anticoagulant treatment for acute
      cardioembolic stroke is uncertain. We performed an updated meta-analysis of all
      randomized trials to obtain the best estimates of the efficacy and safety of
      anticoagulants for the initial treatment of acute cardioembolic stroke. METHODS:
      Using electronic and manual searches of the literature, we identified randomized
      trials comparing anticoagulants (unfractionated heparin or low-molecular-weight
      heparin or heparinoids), started within 48 hours, with other treatments (aspirin
      or placebo) in patients with acute ischemic cardioembolic stroke. Two reviewers
      independently selected studies and extracted data on study design, quality, and
      clinical outcomes, including death or disability, all strokes, recurrent ischemic
      stroke, and cerebral symptomatic bleeding. Odds ratios for individual outcomes
      were calculated for each trial and data from all the trials were pooled using the
      Mantel-Haenszel method. RESULTS: Seven trials, involving 4624 patients with acute
      cardioembolic stroke, met the criteria for inclusion. Compared with other
      treatments, anticoagulants were associated with a nonsignificant reduction in
      recurrent ischemic stroke within 7 to 14 days (3.0% versus 4.9%, odds ratio 0.68,
      95% CI: 0.44 to 1.06, P=0.09, number needed to treat=53), a significant increase
      in symptomatic intracranial bleeding (2.5% versus 0.7%, odds ratio 2.89; 95% CI:
      1.19 to 7.01, P=0.02, number needed to harm=55), and a similar rate of death or
      disability at final follow up (73.5% versus 73.8%, odds ratio 1.01; 95% CI: 0.82
      to 1.24, P=0.9). CONCLUSIONS: Our findings indicate that in patients with acute
      cardioembolic stroke, early anticoagulation is associated with a nonsignificant
      reduction in recurrence of ischemic stroke, no substantial reduction in death and
      disability, and an increased intracranial bleeding.

PMID- 17204682
TI  - Predictors of outcome in patients with cerebral venous thrombosis and
      intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Although intracerebral hemorrhages are frequent in
      patients with cerebral venous thrombosis, and lead to worse outcome, predictors
      of outcome in cerebral venous thrombosis patients with intracerebral hemorrhages
      have never been evaluated in adequately powered studies. METHODS: This study was
      conducted as a part of the International Study on Cerebral Vein and Dural Sinus
      Thrombosis. We evaluated predictors of outcome in cerebral venous thrombosis
      patients who had an "early intracerebral hemorrhage," ie, intracerebral
      hemorrhages already present at time of diagnosis of cerebral venous thrombosis by
      a logistic regression analysis, with a modified Rankin scale 3 to 6 at month 6 as
      dependent variable. The same analysis was performed with "delayed intracerebral
      hemorrhages," ie, intracerebral hemorrhages that occurred after the diagnosis of
      cerebral venous thrombosis, as dependent variable. RESULTS: Of 624 patients
      recruited in International Study on Cerebral Vein and Dural Sinus Thrombosis, 245
      (39%) had an early intracerebral hemorrhage: at month 6, 51 (21%) of them had a
      modified Rankin Scale 3 to 6. Independent predictors of having modified Rankin
      scale 3 to 6 at month 6 were older age (adjusted odds ratio for 1-year increase
      in age, 1.05; 95% CI, 1.02 to 1.08); male gender (adjusted odds ratio, 3.25; 95%
      CI, 1.29 to 8.16); having a deep cerebral venous system thrombosis (adjusted odds
      ratio, 5.43; 95% CI, 1.67 to 17.61) or a right lateral sinus thrombosis (adjusted
      odds ratio, 2.56; 95% CI, 1.03 to 6.40); and having a motor deficit (adjusted
      odds ratio, 2.94; 95% CI, 1.21 to 7.10). Of the 36 patients who had a delayed
      intracerebral hemorrhage, those who had a modified Rankin scale 3 to 6 at month 6
      were less likely to have received heparin at the acute stage, and more likely to
      have had early intracerebral hemorrhage. CONCLUSIONS: Among patients with early
      intracerebral hemorrhage, those who were older, men, had a thrombosis of the deep
      cerebral venous system or of the right lateral sinus, and a motor deficit were at
      higher risk for death or dependency at month 6. This subgroup of patients with
      predictors of poor outcome can be the target for new therapeutic strategies.

PMID- 17204683
TI  - Two tales: hemorrhagic transformation but not parenchymal hemorrhage after
      thrombolysis is related to severity and duration of ischemia: MRI study of acute
      stroke patients treated with intravenous tissue plasminogen activator within 6
      hours.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage represents the most feared
      complication of treatment with intravenous tissue plasminogen activator. We
      studied whether perfusion-weighted imaging and diffusion-weighted imaging has the
      potential to identify patients at risk of severe intracerebral hemorrhage after
      treatment with intravenous tissue plasminogen activator. METHODS: We analyzed
      data of prospectively studied MRI selected acute ischemic stroke patients treated
      with intravenous tissue plasminogen activator within 6 hours. All patients were
      examined by perfusion- and diffusion-weighted imaging < or =6 hours. Perfusion-
      and diffusion-weighted imaging lesion volumes were calculated. Hemorrhagic
      transformation was assessed on follow-up CT or MRI and diagnosed as hemorrhagic
      transformation, parenchymal hemorrhage, or symptomatic intracerebral hemorrhage
      according to ECASS II criteria. RESULTS: Of 152 patients, hemorrhagic
      transformation was seen in 60 (39.5%), parenchymal hemorrhage in 15 (9.9%), and
      symptomatic intracerebral hemorrhage in 4 (2.6%). Multiple logistic regression
      analysis identified onset to treatment time after 3 to 6 hours (P<0.001), a
      larger perfusion-weighted imaging lesion volume (P=0.002), and, as a tendency, a
      higher score on the National Institutes of Health Stroke Scale on admission
      (P=0.068) as independent predictors of hemorrhagic transformation. Neither MRI
      lesion volumes nor severity of symptoms, but rather only an older age tended to
      be associated with parenchymal hemorrhage (P=0.087). CONCLUSIONS: Our results
      further support the concept of a different pathogenesis for hemorrhagic
      transformation and parenchymal hemorrhage. Whereas hemorrhagic transformation
      should be regarded as a clinically irrelevant epiphenomenon of ischemic damage
      and reperfusion, parenchymal hemorrhage appears to be related to biologic effects
      of tissue plasminogen activator and other pre-existing pathologic conditions,
      which deserve further investigation.

PMID- 17204684
TI  - Glycated hemoglobin and risk of stroke in people without known diabetes in the
      European Prospective Investigation into Cancer (EPIC)-Norfolk prospective
      population study: a threshold relationship?
AB  - BACKGROUND AND PURPOSE: Diabetes is a well-recognized risk factor for
      cardiovascular diseases. Evidence suggests a linear relationship between blood
      glucose and myocardial infarction, even at blood glucose concentrations below the
      threshold for diabetes. The relationship between blood glucose concentration and
      stroke in people without established diabetes has been studied less extensively.
      METHODS: We examined the prospective relationship between usual blood glucose
      level measured by glycohemoglobin (HbA(1c)) concentrations and incident stroke
      risk in a general population without diabetes and stroke at baseline assessment
      in the European Prospective Investigation Into Cancer (EPIC)-Norfolk. RESULTS: A
      total of 10,489 men and women aged 40 to 79 years at baseline were followed up
      (mean=8.5 years). Mean age, systolic and diastolic blood pressure, body mass
      index, total cholesterol, triglycerides, and proportion of current smokers
      increased and mean high-density lipoprotein cholesterol decreased with increasing
      HbA(1c) concentrations. There were 164 incident strokes identified over 88 652
      person-years. After adjustment for age, sex, and cardiovascular risk factors, the
      relative risks (95% CI) for stroke for participants with HbA(1c) concentrations
      5% to 5.4%, 5.5% to 6.9%, and > or =7% were 0.78 (0.50 to 1.22), 0.83 (0.54 to
      1.27), and 2.83 (1.40 to 5.74), respectively, compared with those with HbA(1c)
      <5%. CONCLUSIONS: In contrast to the continuous linear relationship observed
      between blood glucose level and coronary heart disease risk, the association
      between blood glucose level and stroke risk appears to be more consistent with a
      threshold relationship. These observations may give insights into the differing
      pathogenesis of different vascular diseases.

PMID- 17204685
TI  - Stroke symptoms and the decision to call for an ambulance.
AB  - BACKGROUND AND PURPOSE: Few acute stroke patients are treated with alteplase,
      partly because of significant prehospital delays after symptom onset. The aim of
      this study was to determine among ambulance-transported stroke patients factors
      associated with stroke recognition and factors associated with a call for
      ambulance assistance within 1 hour from symptom onset. METHODS: For 6 months in
      2004, all ambulance-transported stroke or transient ischemic attack patients
      arriving from a geographically defined region in Melbourne (Australia) to 1 of 3
      hospital emergency departments were assessed. Tapes of the call for ambulance
      assistance were analyzed and the patient and the caller were interviewed.
      RESULTS: One hundred ninety-eight patients were included in the study. Stroke was
      reported as the problem in 44% of ambulance calls. Unprompted stroke recognition
      was independently associated with facial droop (P=0.015) and a history of stroke
      or transient ischemic attack (P<0.001). More than half of the calls for ambulance
      assistance were made within 1 hour from symptom onset and only 43% of these
      callers spontaneously identified the problem as "stroke." Factors independently
      associated with a call within 1 hour were: speech problems (P=0.009), caller
      family history of stroke (P=0.017), and the patient was not alone at symptom
      onset (P=0.018). CONCLUSIONS: Stroke was reported as the problem (unprompted) by
      <50% of callers. Fewer than half the calls were made within 1 hour from symptom
      onset. Interventions are needed to more strongly link stroke recognition to
      immediate action and increase the number of stroke patients eligible for acute
      treatment.

PMID- 17204686
TI  - Endothelial function and white matter hyperintensities in older adults with
      cardiovascular disease.
AB  - BACKGROUND AND PURPOSE: The presence of white matter hyperintensities on brain
      MRI is common among elderly individuals. Previous research suggests that
      cardiovascular risk factors are associated with increased white matter
      hyperintensities. Examining the role of direct physiological measures of vascular
      function will help to clarify the vascular mechanisms related to white matter
      hyperintensities. The aim of the present study was to examine the association
      between endothelial-dependent and endothelial-independent vasodilatation and
      white matter hyperintensity volume. METHODS: Twenty-five older adults with a
      range of cardiovascular diseases underwent brain MRI and completed assessments of
      blood vessel integrity using endothelial-dependent and independent flow-mediated
      dilation of the brachial artery. A semi-automated pixel-based method was used to
      quantify total brain volume and white matter hyperintensity volume, with white
      matter hyperintensity volume corrected for total brain volume. The association
      between measures of flow-mediated dilation and log-transformed white matter
      hyperintensities was examined. RESULTS: Correlation analysis revealed that
      endothelial-dependent vasodilatation was significantly and inversely associated
      with white matter hyperintensity volume. In contrast, endothelial-independent
      vasodilatation was not associated with white matter hyperintensities. Neither
      endothelial-dependent nor endothelial-independent vasodilatation was associated
      with total brain volume. CONCLUSIONS: These data provide preliminary evidence
      that the integrity of the vascular endothelium is associated with white matter
      hyperintensities in older adults with cardiovascular disease. Impaired vascular
      function may be one mechanism that contributes to the development of white matter
      hyperintensities in the brain. Additional longitudinal research combining
      measures of vessel function, neuroimaging and cognition will be helpful in
      clarifying this potential mechanism.

PMID- 17204687
TI  - Asymmetric dimethylarginine in cerebral small vessel disease.
AB  - BACKGROUND AND PURPOSE: Endothelial dysfunction may play a causal role in
      cerebral small vessel disease (SVD). Asymmetric dimethylarginine (ADMA), a
      circulating endogenous inhibitor of nitric oxide, has been implicated in
      endothelial dysfunction, particularly in hyperhomocystinemia, a known risk factor
      for SVD. We determined if ADMA was elevated in SVD, correlated with disease
      severity, and interacted with homocysteine. METHODS: ADMA and homocysteine levels
      were determined in 47 consecutive symptomatic SVD patients and 38 controls. SVD
      was graded by leukoariosis severity and number of lacunar infarcts. RESULTS: Mean
      (and SD) ADMA was higher in SVD patients compared with controls (0.814 [0.145]
      versus 0.747 [0.184] micromol/L; P=0.014) after controlling for age, gender,
      vascular risk factors, and creatinine clearance. Additionally controlling for
      homocysteine had only a small effect on this relationship (P=0.055). Mean
      homocysteine was higher in SVD cases compared with controls (15.14 [5.59] versus
      12.49 [4.15] micromol/L; P=0.035). Leukoariosis grade correlated positively with
      ADMA (P=0.026) and homocysteine (P=0.003). Lacunar grade correlated with
      homocysteine (P=0.017), but not ADMA. CONCLUSIONS: ADMA is independently
      associated with SVD and correlates with leukoariosis severity.

PMID- 17204688
TI  - The Thr715Pro polymorphism of the P-selectin gene is not associated with ischemic
      stroke risk.
AB  - BACKGROUND AND PURPOSE: A Thr>Pro polymorphism at codon 715 in the coding region
      of the P-selectin gene has recently been described. Individuals carrying the
      Pro715 allele were reported to have a reduced risk of myocardial infarction. A
      possible association of this polymorphism with the risk of ischemic stroke is
      currently under discussion. METHODS: We investigated the prevalence of the 715
      Thr>Pro polymorphism in 450 patients aged younger than 60 years with ischemic
      stroke or transient ischemic attack and in 450 controls without vascular disease
      matched for age and gender. We also investigated possible interactions of the
      polymorphism with other vascular risk factors, stroke severity and stroke
      etiology. RESULTS: The distribution of the two allelic variants of the 715Thr>Pro
      polymorphism did not differ significantly between patients and control subjects
      (78% versus 81% for Thr/Thr, 21% versus 18% for Thr/Pro and 1% versus 1% for
      Pro/Pro in patients and controls, respectively; adjusted odds ratio for carriers
      of the C allele: 1.0 [0.8 to 1.2; P=0.695]). We found no significant interaction
      of this polymorphism with vascular risk factors, stroke severity, or stroke
      etiology. CONCLUSIONS: Our study supports results from previous investigation
      showing that the 715Thr>Pro polymorphism of the P-selectin gene was not
      associated with a risk or clinical characteristics of ischemic stroke.

PMID- 17204689
TI  - Systematic review and meta-analysis of the efficacy of tirilazad in experimental
      stroke.
AB  - BACKGROUND AND PURPOSE: Tirilazad is a candidate neuroprotective drug with
      reported efficacy in animal models of stroke that was, however, without benefit
      in clinical trials. This apparent contradiction might be explained if the animal
      studies were falsely positive, if the clinical trials were falsely negative, or
      if tirilazad was not tested under the same conditions in animal and clinical
      studies. Here we use systematic review and meta-analysis to describe the
      characteristics and limits to the neuroprotective action of tirilazad in animal
      models of stroke. METHODS: Systematic review and meta-analysis of studies
      describing the efficacy of tirilazad in animal models of focal ischemia, in which
      outcome was measured as infarct volume and/or neurological score. Weighted mean
      difference random effects meta-analysis was used to measure overall efficacy in
      prespecified subgroups. RESULTS: Eighteen studies describing outcome in 544
      animals were identified. Study quality (median score, 5/10; interquartile range,
      4 to 6) was similar to that seen in systematic reviews of other candidate
      neuroprotective drugs. Tirilazad reduced infarct volume by 29.2% (95% confidence
      interval 21.1% to 37.2%) and improved neurobehavioral score by 48.1% (95%
      confidence interval 29.3% to 66.9%). CONCLUSIONS: Tirilazad may have substantial
      efficacy in animal models of stroke, but this conclusion must be qualified
      because of the presence of potential sources of bias.

PMID- 17204691
TI  - Spatial dose mapping for individualizing radioiodine treatment.

PMID- 17204692
TI  - What is in a number? The FDG lumped constant in the rat brain.

PMID- 17204693
TI  - Utility of 18F-FDG PET/CT uptake patterns in Waldeyer's ring for differentiating
      benign from malignant lesions in lateral pharyngeal recess of nasopharynx.
AB  - Focally increased (18)F-FDG uptake in the lateral pharyngeal recess (LPR) of the
      nasopharynx due to a benign or malignant lesion is not an uncommon finding on PET
      images. The aim of this study was to evaluate whether, on PET/CT images, (18)F
      FDG uptake occurs with characteristic patterns and intensities in various regions
      of Waldeyer's ring that can improve our ability to differentiate benign from
      malignant lesions. METHODS: Data generated from the (18)F-FDG PET/CT images of
      1,628 subjects in our cancer-screening program were analyzed. Increased uptake in
      the LPR was observed in 80 subjects (4.9%) presenting with benign lesions,
      including 53 subjects without and 27 subjects with symptoms of upper airway
      discomfort. In addition, 30 healthy controls and 21 patients with newly diagnosed
      nasopharyngeal carcinoma were recruited for this study. Visual uptake,
      measurements of the lesions' standardized uptake value (SUV), and any
      abnormalities on PET/CT were evaluated. The receiver-operating-characteristic
      curve and area under the curve were applied to evaluate the discriminating power.
      RESULTS: Increased (18)F-FDG uptake (SUV, mean +/- SD) was found in the LPR, with
      a statistically significant (P < 0.001) difference between benign lesions (3.0 +/
      1.16) and malignant lesions (7.03 +/- 3.83). However, associated increased
      uptake exclusively in the palatine tonsil, lingual tonsil, and submandibular
      gland was found in both asymptomatic and symptomatic subjects. The ratio of LPR
      uptake to palatine tonsil uptake (N/P ratio) in benign lesions (0.81 +/- 0.37)
      was significantly (P < 0.001) lower than that in malignant lesions (2.30 +/-
      1.62). Higher incidences of asymmetric (18)F-FDG LPR uptake, cervical lymph node
      uptake, and asymmetric wall thickening of the LPR on CT were observed in patients
      with nasopharyngeal carcinoma. When an SUV of less than 3.9 and an N/P ratio of
      less than 1.5 were used as cutoff points in subjects showing the combination of
      symmetric uptake in the LPR and normal or symmetric wall thickening, and
      detectable lymph node uptake, the area under the curve for benign lesions on
      PET/CT was 0.932 +/- 0.042 (95% confidence interval, 0.86-0.98), with a
      sensitivity of 90.4% and a specificity of 93.8%. CONCLUSION: The intensity and
      patterns of (18)F-FDG uptake in various regions of Waldeyer's ring along with CT
      scan findings provide a feasible modality to differentiate benign from malignant
      nasopharyngeal lesions.

PMID- 17204694
TI  - Clinical significance of small pulmonary nodules with little or no 18F-FDG uptake
      on PET/CT images of patients with nonthoracic malignancies.
AB  - Small pulmonary nodules with little or no perceptible (18)F-FDG uptake are
      relatively common findings on combined PET/CT images of patients with nonthoracic
      malignancies. Interpreting such nodules is often a diagnostic challenge, and this
      study aimed to evaluate the clinical significance of the nodules. METHODS:
      Patients with pulmonary nodules < or =1 cm in diameter showing no (18)F-FDG
      uptake or uptake less than the mediastinal background were included. Nodules with
      clearly benign or metastatic findings on CT were excluded. One hundred twenty-one
      patients had either tissue confirmation or clinical follow-up with additional
      chest images. The subjects were studied by 3 variables: (i) solitary versus
      multiple nodules, (ii) presence of accompanying benign lung lesion versus
      absence, and (iii) imperceptible (18)F-FDG uptake versus faint (18)F-FDG uptake.
      The malignancy rates were calculated for each variable. RESULTS: Of the 121
      patients, 24 had malignancy, with a strong possibility of pulmonary metastasis
      (19.8%). Six of the 44 patients with solitary nodules (13.6%) and 18 of the 77
      patients with multiple nodules (23.4%) had malignancies, though there was no
      statistically significant difference in the incidences of malignancy between the
      solitary and multiple groups. On the other hand, there was a statistically
      significant difference (P = 0.040) between the accompanying lung lesion present
      (8.3%) and absent (24.7%) groups. No statistically significant difference was
      noted between the (18)F-FDG uptake imperceptible group and faint (18)F-FDG uptake
      group (20.7% vs. 17.2%). CONCLUSION: For patients with incidental lung nodules of
      indeterminate nature with no (18)F-FDG uptake or uptake less than that of the
      mediastinum on PET/CT images, >19% of the cases turned out to be malignant. The
      nodule was more likely to be malignant when no other benign pulmonary lesions
      could be identified elsewhere in the lung field. Thus, regardless of the number
      of nodules and (18)F-FDG uptake, tissue confirmation or close imaging follow-up
      is necessary when small nodules with imperceptible or faint (18)F-FDG activity
      are present on the PET/CT images, especially in the absence of accompanying
      benign lung lesions.

PMID- 17204695
TI  - Deep-inspiration breath-hold PET/CT of the thorax.
AB  - The goal of this study was to describe our initial experience with the deep
      inspiration breath-hold (DIBH) technique in combined PET/CT of the thorax. This
      article presents particular emphasis on the technical aspects required for
      clinical implementation. METHODS: In the DIBH technique, the patient is verbally
      coached and brought to a reproducible deep inspiration breath-hold level. The
      first "Hold" period, which refers to the CT session, is considered as the
      reference. This is followed by 9- to 20-s independent breath-hold PET
      acquisitions. The goal is to correct for respiratory motion artifacts and,
      consequently, improve the tumor quantitation and localization on the PET/CT
      images and inflate the lungs for possible improvement in the detection of
      subcentimeter pulmonary nodules. A physicist monitors and records patient
      breathing during PET/CT acquisition using a motion tracker. Patient breathing
      traces obtained during acquisition are examined on the fly to assess the
      reproducibility of the technique. RESULTS: Data from 8 patients, encompassing 10
      lesions, were analyzed. Visual inspection of fused PET/CT images showed improved
      spatial matching between the 2 modalities, reduced motion artifacts especially in
      the diaphragm, and increased the measured standardized uptake value (SUV)
      attributed to reduced motion blurring, as compared with the standard clinical
      PET/CT images. CONCLUSION: The practice of DIBH PET/CT is feasible in a clinical
      setting. With this technique, consistent lung inflation levels are achieved
      during PET/CT sessions, as judged by both motion tracker and verification of
      spatial matching between PET and CT images. Breathing-induced motion artifacts
      are significantly reduced using DIBH compared with free breathing, enabling
      better target localization and quantitation. The DIBH technique showed an
      increase in the median SUV by 32.46%, with a range from 4% to 83%, compared with
      SUVs measured on the clinical images. The median percentage reduction in the PET
      to-CT lesions' centroids was 26.6% (range, 3%-50%).

PMID- 17204696
TI  - Extended studies of the striatal uptake of 99mTc-NC100697 in healthy volunteers.
AB  - This study evaluates a new formulation of a (99m)Tc-labeled tropane derivate,
      (99m)Tc-NC100697, in a human volunteer study. METHODS: Eighty healthy subjects
      (39 females, 41 males) underwent MRI and SPECT (injected dose [mean +/- SD], 10.6
      +/- 1.4 MBq/kg). Forty subjects were investigated 30, 90, 180, 240, 360, and 480
      min after injection, and another 40 subjects were imaged 240 min after injection.
      Specific striatal binding was assessed using 3 different approaches: 3
      dimensional volumes of interest (VOIs) drawn on the coregistered MRI scans,
      manually placed predefined 2-dimensional regions of interest (ROIs), and observer
      independent fully automated 3-dimensional VOI analyses based on coregistration of
      scans with a mean template of controls. Specific striatal dopamine transporter
      (DAT) binding was estimated for cohorts of ages of 21-30, 31-40, 41-50, 51-60, 61
      70, and 71-80 y. The relationship between age and DAT binding was analyzed with
      linear, "broken-stick," exponential, and logarithmic regression. RESULTS: Serial
      SPECT scans revealed increasing values of specific DAT binding over time.
      Consideration of all important variables suggests an optimum imaging time at 4 h
      after injection. Average DAT binding for the total population was 1.1 +/- 0.2
      (striatum), 1.3 +/- 0.2 (caudate), and 1.1 +/- 0.2 (putamen), with mean putamen
      to-caudate ratios of 0.83 +/- 0.08 (manual 2-dimensional ROI method). A
      significant age dependency of striatal DAT binding, best described by a broken
      stick (break-point age, 48 y) or logarithmic regression (both r = 0.76), with a
      lower decline observed in older than in younger subjects. Female subjects
      presented with slightly higher binding ratios than male subjects, more pronounced
      in pre- than in postmenopausal women. There was a high correlation between the 3
      semiquantitative evaluations. CONCLUSION: The current study has demonstrated the
      effective use of (99m)Tc-NC100697 for estimating presynaptic striatal DAT
      binding. The comparison of different semiquantification methods showed that in
      clinical routine work, this tracer can be reliably evaluated without individual
      MRI data. Age and a slight sex dependency (especially in premenopausal women) of
      (99m)Tc-NC100697 binding should be taken into consideration. The data generated
      in this phase 1 study provides a basis for an age- and sex-matched normal
      database.

PMID- 17204697
TI  - 18F-FDG PET and PET/CT in fever of unknown origin.
AB  - Fever of unknown origin (FUO) was originally defined as recurrent fever of 38.3
      degrees C or higher, lasting 2-3 wk or longer, and undiagnosed after 1 wk of
      hospital evaluation. The last criterion has undergone modification and is now
      generally interpreted as no diagnosis after appropriate inpatient or outpatient
      evaluation. The 3 major categories that account for most FUOs are infections,
      malignancies, and noninfectious inflammatory diseases. The diagnostic approach in
      FUO includes repeated physical investigations and thorough history-taking
      combined with standardized laboratory tests and simple imaging procedures.
      Nevertheless, there is a need for more complex or invasive techniques if this
      strategy fails. This review describes the impact of (18)F-FDG PET in the
      diagnostic work-up of FUO. (18)F-FDG accumulates in malignant tissues but also at
      the sites of infection and inflammation and in autoimmune and granulomatous
      diseases by the overexpression of distinct facultative glucose transporter (GLUT)
      isotypes (mainly GLUT-1 and GLUT-3) and by an overproduction of glycolytic
      enzymes in cancer cells and inflammatory cells. The limited data of prospective
      studies indicate that (18)F-FDG PET has the potential to play a central role as a
      second-line procedure in the management of patients with FUO. In these studies,
      the PET scan contributed to the final diagnosis in 25%-69% of the patients. In
      the category of infectious diseases, a diagnosis of focal abdominal, thoracic, or
      soft-tissue infection, as well as chronic osteomyelitis, can be made with a high
      degree of certainty. Negative findings on (18)F-FDG PET essentially rule out
      orthopedic prosthetic infections. In patients with noninfectious inflammatory
      diseases, (18)F-FDG PET is of importance in the diagnosis of large-vessel
      vasculitis and seems to be useful in the visualization of other diseases, such as
      inflammatory bowel disease, sarcoidosis, and painless subacute thyroiditis. In
      patients with tumor fever, diseases commonly detected by (18)F-FDG PET include
      Hodgkin's disease and aggressive non-Hodgkin's lymphoma but also colorectal
      cancer and sarcoma. (18)F-FDG PET has the potential to replace other imaging
      techniques in the evaluation of patients with FUO. Compared with labeled white
      blood cells, (18)F-FDG PET allows diagnosis of a wider spectrum of diseases.
      Compared with (67)Ga-citrate scanning, (18)F-FDG PET seems to be more sensitive.
      It is expected that PET/CT technology will further improve the diagnostic impact
      of (18)F-FDG PET in the context of FUO, as already shown in the oncologic
      context, mainly by improving the specificity of the method.

PMID- 17204698
TI  - A preliminary study of anti-1-amino-3-18F-fluorocyclobutyl-1-carboxylic acid for
      the detection of prostate cancer.
AB  - We evaluated the feasibility of anti-1-amino-3-(18)F-fluorocyclobutyl-1
      carboxylic acid (anti-(18)F-FACBC) in diagnosing prostate cancer (PCa), using a
      rat orthotopic prostate cancer transplantation (OPCT) model. Furthermore, using
      in vivo experiments, we examined the potential of anti-(18)F-FACBC for
      differentiating between PCa and inflammation and between PCa and benign prostatic
      hyperplasia (BPH). METHODS: The OPCT model was developed by transplanting DU145,
      a human PCa cell line, into the ventral prostate of athymic F344 rats. To develop
      a dual PCa and inflammation (DPCI) model, MAT-Ly-Lu-B2--a rat PCa cell line--was
      transplanted subcutaneously into male Copenhagen rats. Streptozotocin was
      injected into the hind footpad of these rats for inducing popliteal
      lymphadenitis. For inducing the BPH, normal F344 rats were castrated and injected
      subcutaneously with testosterone propionate. In biodistribution studies, the rats
      were injected with anti-(18)F-FACBC or (18)F-FDG and sacrificed at 15 or 60 min
      after injection. We performed dynamic small-animal PET of the abdominal portion
      of the OPCT rats for 60 min after the injection of anti-(18)F-FACBC or (18)F-FDG.
      RESULTS: The biodistribution in the OPCT rats at 60 min after injection showed
      that the uptake of anti-(18)F-FACBC and (18)F-FDG into the PCa tissue was 1.58 +/
      0.40 %ID/cm(3) (percentage injected dose per cm(3)) and 1.48 +/- 0.90 %ID/cm(3),
      respectively (P > 0.05). The accumulation of anti-(18)F-FACBC in the urinary
      bladder at 60 min after injection was 3.09 +/- 1.43 %ID/cm(3), whereas that of
      (18)F-FDG was 69.31 +/- 16.55 %ID/cm(3) (P < 0.05). Consequently, small-animal
      imaging with anti-(18)F-FACBC facilitated the visualization of the PCa tissue of
      the OPCT rats with higher contrast than (18)F-FDG. Furthermore, in comparison
      with (18)F-FDG, apparently higher ratios of PCa to inflammation and PCa to BPH
      accumulation of anti-(18)F-FACBC were demonstrated in the animal models.
      CONCLUSION: FACBC PET is believed to be useful not only for the visualization of
      human PCa but also for differentiating between PCa and inflammation and between
      PCa and BHP.

PMID- 17204699
TI  - Initial experience with the radiotracer anti-1-amino-3-18F-fluorocyclobutane-1
      carboxylic acid with PET/CT in prostate carcinoma.
AB  - Conventional imaging techniques have serious limitations in the detection,
      staging, and restaging of prostate carcinoma. Anti-1-amino-3-(18)F
      fluorocyclobutane-1-carboxylic acid (anti-(18)F-FACBC)is a synthetic l-leucine
      analog that has excellent in vitro uptake within the DU-145 prostate carcinoma
      cell line and orthotopically implanted prostate tumor in nude rats. There is
      little renal excretion compared with (18)F-FDG. The present study examines anti
      (18)F-FACBC uptake in patients with newly diagnosed and recurrent prostate
      carcinoma. METHODS: Fifteen patients with a recent diagnosis of prostate
      carcinoma (n = 9) or suspected recurrence (n = 6) underwent 65-min dynamic PET/CT
      of the pelvis after intravenous injection of 300-410 MBq anti-(18)F-FACBC
      followed by static body images. Each study was evaluated qualitatively and
      quantitatively. Maximum standardized uptake values were recorded in the prostate
      or prostate bed, and within lymph nodes at 4.5 min (early) and 20 min (delayed),
      and correlated with clinical, imaging and pathologic follow-up. Time-activity
      curves were also generated for benign and malignant tissue. RESULTS: In the 8
      patients with newly diagnosed prostate carcinoma who underwent dynamic scanning,
      visual analysis correctly identified the presence or absence of focal neoplastic
      involvement in 40 of 48 prostate sextants. Pelvic nodal status correlated with
      anti-(18)F-FACBC findings in 7 of 9 patients and was indeterminate in 2 of 9. In
      all 4 patients in whom there was proven recurrence, visual analysis was
      successful in identifying disease (1 prostate bed, 3 extraprostatic). In 3 of
      these patients, (111)In-capromab-pendetide had no significant uptake at nodal and
      skeletal foci. Malignant lymph node uptake in both the staging and restaging
      patients was significantly higher than benign nodal uptake. Though uptake faded
      with time, in all 6 patients with either lymph node metastases or recurrent
      prostate bed carcinoma, there was intense persistent uptake at 65 min.
      CONCLUSION: Anti-(18)F-FACBC is a promising radiotracer for imaging prostate
      carcinoma. Radiotracer uptake was demonstrated in primary and metastatic disease.
      Future research should investigate the mechanism of radiotracer uptake in normal
      and pathologic tissue and develop a clinical imaging strategy for initial staging
      and restaging.

PMID- 17204700
TI  - Synthesis and biologic evaluation of 64Cu-labeled rhenium-cyclized alpha-MSH
      peptide analog using a cross-bridged cyclam chelator.
AB  - Early detection of cutaneous melanoma is essential, as prognosis with metastatic
      melanoma is poor. Previous studies showed that (64)Cu-DOTA-ReCCMSH(Arg(11)) (DOTA
      is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), a cyclic
      analog of alpha-melanocyte-stimulating hormone (alpha-MSH), has the potential for
      the detection of malignant melanoma using PET. However, (64)Cu-DOTA
      ReCCMSH(Arg(11)) demonstrated high background in nontarget tissues due to the in
      vivo instability of the Cu-DOTA moiety. CBTE2A (CBTE2A is 4,11-bis(carboxymethyl)
      1,4,8,11-tetraazabicyclo[6.6.2]hexadecane) has been shown to be a more stable
      copper chelate with improved in vivo stability, resulting in an improvement in
      clearance from nontarget tissues. The goal of this study was to conjugate CBTE2A
      to the alpha-MSH targeting ReCCMSH(Arg(11)) peptide for labeling to (64)Cu and to
      investigate whether the increased metal-chelate stability with CBTE2A would
      improve imaging quality. METHODS: The recyclized peptide CBTE2A-ReCCMSH(Arg(11))
      was synthesized using a solid-phase peptide synthesizer followed by rhenium
      cyclization. In vivo characteristics of (64)Cu-CBTE2A-ReCCMSH(Arg(11)) were
      examined with small-animal PET and acute biodistribution studies in B16/F1 tumor
      bearing mice. RESULTS: Biodistribution studies showed high and rapid receptor
      mediated tumor uptake with values similar to those reported for (64)Cu- and (86)Y
      labeled DOTA-ReCCMSH(Arg(11)). Nontarget organ concentration for (64)Cu-CBTE2A
      ReCCMSH(Arg(11)) was considerably lower than that of the (64)Cu-DOTA analog,
      resulting in significantly higher tumor-to-nontarget tissue ratios. Compared with
      (86)Y-DOTA-ReCCMSH(Arg(11)), (64)Cu-CBTE2A-ReCCMSH(Arg(11)) demonstrated
      increased tumor retention and kidney clearance. Small-animal PET images showed
      that the tumor could be clearly visualized at all time points (0.5-24 h).
      CONCLUSION: Our data suggest the superior stability of the (64)Cu-CBTE2A moiety
      compared with (64)Cu-DOTA, making (64)Cu-CBTE2A-ReCCMSH(Arg(11)) an ideal
      candidate for the PET of malignant melanoma.

PMID- 17204701
TI  - 99mTc- and 111In-labeled alpha-melanocyte-stimulating hormone peptides as imaging
      probes for primary and pulmonary metastatic melanoma detection.
AB  - It is highly desired to develop new imaging probes for early detection of
      melanoma as early diagnosis and prompt surgical removal are a patient's best hope
      for a cure. The purpose of this study was to determine whether (99m)Tc- and
      (111)In-labeled alpha-melanocyte-stimulating hormone (alpha-MSH) peptides could
      be used as imaging probes for primary and metastatic melanoma using dual-modality
      micro-SPECT/CT detection. METHODS: [Cys(3,4,10),d-Phe(7),Arg(11)]alpha-MSH(3-13)
      [(Arg(11))CCMSH] and [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
      acid]Re(Arg(11))CCMSH [DOTA-Re(Arg(11))CCMSH] were labeled with (99m)Tc and
      (111)In. The pharmacokinetics of (99m)Tc-(Arg(11))CCMSH were examined in B16/F1
      flank and B16/F10 pulmonary metastatic murine melanoma-bearing C57 mice. The
      biodistribution of (111)In-DOTA-Re(Arg(11))CCMSH was performed in B16/F10
      pulmonary metastatic murine melanoma-bearing C57 mice. SPECT/CT of (99m)Tc
      (Arg(11))CCMSH and (111)In-DOTA-Re(Arg(11))CCMSH was determined in B16/F1 flank
      and B16/F10 pulmonary metastatic murine melanoma-bearing C57 mice. RESULTS:
      (99m)Tc-(Arg(11))CCMSH and (111)In-DOTA-Re(Arg(11))CCMSH exhibited high tumor
      uptakes (14.03 +/- 2.58 percentage injected dose/gram [%ID/g] at 1 h after
      injection and 17.29 +/- 2.49 %ID/g at 2 h after injection) in B16/F1 melanoma
      bearing mice, and the flank melanoma tumors were clearly imaged by micro
      SPECT/CT. Nontarget organ uptakes were considerably lower except for the kidneys.
      B16/F10 pulmonary melanoma metastases were also clearly visualized by micro
      SPECT/CT using (99m)Tc-(Arg(11))CCMSH or (111)In-DOTA-Re(Arg(11))CCMSH as the
      imaging probe. (99m)Tc-(Arg(11))CCMSH exhibited images with greater resolution of
      metastatic melanoma lesions compared with (111)In-DOTA-Re(Arg(11))CCMSH.
      CONCLUSION: The favorable tumor imaging properties of (99m)Tc-(Arg(11))CCMSH and
      (111)In-DOTA-Re(Arg(11))CCMSH highlighted their potential as novel probes for
      primary and metastatic melanoma detection.

PMID- 17204702
TI  - In vivo evaluation of P-glycoprotein modulation of 8 PET radioligands used
      clinically.
AB  - P-glycoprotein (P-gp) regulates the ability of endogenous and exogenous compounds
      to cross the blood-brain barrier. We investigated whether PET tracers used
      clinically for studying brain function are affected by P-gp. METHODS: Modulation
      of 8 radioligands by P-gp was assayed in mice by evaluating the effect of
      treatment with cyclosporine A (CsA) on uptake into the brain (assay 1) and the
      effect of treatment with a cold ligand of the corresponding radioligand on uptake
      of (11)C-verapamil, a representative radioligand for P-gp (assay 2). Brain-to
      blood ratios were also examined as the other index to correct the delivery of
      radioligands. The radioligands investigated were (11)C-TMSX (adenosine A(2A)
      receptor), (11)C-MPDX (adenosine A(1) receptor), (11)C-PK11195 (peripheral
      benzodiazepine receptor), (11)C-flumazenil (central benzodiazepine receptor),
      (11)C-raclopride (dopamine D(2)-like receptor), (11)C-pyrilamine (histamine H(1)
      receptor), (11)C-PIB (amyloid plaque), and (11)C-donepezil (acetylcholine
      esterase). RESULTS: In assay 1, CsA treatment increased both the uptake and the
      brain-to-blood ratio of (11)C-TMSX, (11)C-MPDX, (11)C-flumazenil, and (11)C
      donepezil among the 8 radioligands. In assay 2, in which 4 cold ligands were
      examined, cold verapamil slightly increased the brain-to-blood ratio of (11)C
      verapamil, but TMSX, MPDX, and MPPF did not increase either parameter.
      CONCLUSION: Assay 1 was suitable for evaluating the P-gp modulation of
      radioligands. Among the 8 radioligands investigated, (11)C-TMSX, (11)C-MPDX,
      (11)C-flumazenil, and (11)C-donepezil were modulated by P-gp.

PMID- 17204703
TI  - Androgen-dependent expression of the gastrin-releasing peptide receptor in human
      prostate tumor xenografts.
AB  - Human prostate cancers (PC) overexpress gastrin-releasing peptide (GRP)
      receptors. This observation suggests that GRP receptors may be used as new
      visualization and treatment modalities for these tumors. Radiolabeled GRP
      receptor-targeting analogs of GRP and bombesin (BN) have successfully been
      developed for these purposes. Expression of GRP receptors in human prostate
      tumors is, however, primarily evaluated in early stages of tumor development and
      information on expression in the more progressive prostate tumors is uncertain.
      To evaluate GRP receptor expression in all stages of PC, we investigated GRP
      receptor expression using a panel of 12 established human PC xenograft models
      representing the different stages of human PC and the effect of antiandrogen
      treatment (castration). METHODS: Human PC xenografts were grown in male nude
      mice, and GRP receptor density in the tumors was evaluated using displacement
      receptor autoradiography with the universal BN receptor analog (125)I-[D
      Tyr(6),beta-Ala(11),Phe(13),Nle(14)]BN(6-14) and the BN analog (111)In-[DTPA
      Pro(1),Tyr(4)]BN (DTPA is diethylenetriaminepentaacetic acid) before and after
      castration. RESULTS: Autoradiography showed high-density GRP receptor expression
      in the androgen-dependent tumors (3/12 models), whereas only very low receptor
      expression was found in the androgen-responsive and -independent tumors (9/12
      models). Castration resulted in GRP receptor downregulation (11%-36% of initial
      values) in the 3 androgen-dependent tumors. CONCLUSION: High GRP receptor density
      was only observed in androgen-dependent PC xenografts, indicating high GRP
      receptor expression in the early, androgen-dependent, stages of prostate tumor
      development and not in later stages. In addition, castration strongly reduced GRP
      receptor expression in androgen-dependent tumors, indicating that GRP receptor
      expression in human PC is androgen-regulated.

PMID- 17204704
TI  - Operational lumped constant for FDG in normal adult male rats.
AB  - We determined an operational value for the lumped constant to be used in
      measurements of the local rate of cerebral glucose use (lCMR(glc)) with FDG in
      normal adult male rats. METHODS: The standard quantitative autoradiographic
      method was used with 2-deoxy-d-(14)C-glucose ((14)C-DG) and with (14)C-FDG in
      awake normal adult male rats. Timed arterial blood samples were drawn for 45 min
      after the bolus and assayed for plasma glucose and (14)C concentrations. At the
      end of the 45-min experimental period, the rats were killed, and their brains
      were removed and divided in half sagittally. One hemisphere was immediately
      frozen and assayed for local (14)C concentrations by quantitative
      autoradiography; the other was weighed, homogenized in t
      octylphenoxypolyethoxyethanol solution, and assayed for (14)C concentrations in
      the whole brain by liquid scintillation counting. Paired rats (3 pairs), one in
      each pair receiving (14)C-DG and the other receiving (14)C-FDG, were studied in
      parallel on the same day. Additional unpaired animals (n = 8) were studied with
      either (14)C-DG or (14)C-FDG but not in parallel on the same day. To calculate
      the lCMR(glc) in rats studied with (14)C-FDG, the rate constants for (14)C-FDG
      were estimated from the (14)C-DG values determined for rats and the (14)C
      FDG/(14)C-DG ratios determined for humans. In all of the rats studied with either
      (14)C-DG or (14)C-FDG, the lCMR(glc) was first calculated in 12 representative
      brain structures with the lumped constant of 0.48 previously determined for (14)C
      DG in rats. The ratio of the lCMR(glc) thus determined with (14)C-FDG to that
      determined with (14)C-DG for each structure was then multiplied by the lumped
      constant for (14)C-DG to estimate the lumped constant for (14)C-FDG. The
      lCMR(glc) and the lumped constant for FDG in the brain as a whole were similarly
      estimated from the tracer concentrations in the brain homogenates. RESULTS: The
      mean values for the lumped constant for FDG were found to be 0.71 and 0.70 in the
      autoradiographic assays and the assays with brain homogenates, respectively.
      CONCLUSION: The appropriate value for the lumped constant to be used in
      determinations of the lCMR(glc) in normal adult male rat studies with (18)F-FDG
      and small-animal PET scanners is 0.71.

PMID- 17204705
TI  - Human biodistribution and radiation dosimetry of the tachykinin NK1 antagonist
      radioligand [18F]SPA-RQ: comparison of thin-slice, bisected, and 2-dimensional
      planar image analysis.
AB  - (18)F-Labeled substance P antagonist-receptor quantifier ([(18)F]SPA-RQ) [2
      fluoromethoxy-5-(5-trifluoromethyl-tetrazol-1-yl)-benzyl]-[(2S,3S)-2-phenyl
      piperidin-3-yl)amine] is a selective radioligand for in vivo quantification of
      tachykinin NK(1) receptors with PET. The aims of this study were to estimate the
      radiation safety profile and relative risks of [(18)F]SPA-RQ with 3 different
      methods of image analysis. METHODS: Whole-body PET images were acquired in 7
      healthy subjects after injection of 192 +/- 7 MBq (5.2 +/- 0.2 mCi) [(18)F]SPA
      RQ. Emission images were serially acquired at multiple time-points from 0 to 120
      min and approximately 180-240 min after injection. Urine samples were collected
      after each imaging session and for 24 h after the last scan to measure excreted
      radioactivity. Horizontal tomographic images were compressed to varying degrees
      in the anteroposterior direction to create 3 datasets: thin-slice, bisected, and
      2-dimensional (2D) planar images. Regions of interest were drawn around visually
      identifiable source organs to generate time-activity curves for each dataset.
      Residence times were determined from these curves, and doses to individual organs
      and the body as a whole were calculated using OLINDA/EXM 1.0. RESULTS: The lungs,
      upper large intestine wall, small intestine, urinary bladder wall, kidneys, and
      thyroid had the highest radiation-absorbed doses. Biexponential fitting of mean
      bladder and urine activity showed that about 41% of injected activity was
      excreted via urine. Assuming a 2.4-h urine voiding interval, the calculated
      effective doses from thin-slice, bisected, and 2D planar images were 29.5, 29.3,
      and 32.3 microSv/MBq (109, 108, and 120 mrem/mCi), respectively. CONCLUSION:
      Insofar as effective dose is an accurate measure of radiation risk, all 3 methods
      of analysis provided quite similar estimates of risk to human subjects. The
      radiation dose was moderate and would potentially allow subjects to receive
      multiple PET scans in a single year. Individual organ exposures varied among the
      3 methods, especially for structures asymmetrically located in an anterior or
      posterior position. Bisected and 2D planar images almost always provided higher
      organ dose estimates than thin-slice images. Thus, either the bisected or 2D
      planar method of analysis appears acceptable for quantifying human radiation
      burden, at least for radioligands with a relatively broad distribution in the
      body and not concentrated in a small number of radiation sensitive organs.

PMID- 17204706
TI  - Segmentation of PET volumes by iterative image thresholding.
AB  - The segmentation of metastatic volumes in PET is usually performed by
      thresholding methods. In a clinical application, the optimum threshold obtained
      from the adaptive thresholding method requires a priori estimation of the lesion
      volume from anatomic images such as CT. We describe an iterative thresholding
      method (ITM) used to estimate the PET volumes without anatomic a priori knowledge
      and its application to clinical images. METHODS: The ITM is based on threshold
      volume curves at varying source-to-background (S/B) ratio acquired from a body
      phantom. The spheres and background were filled either with (18)F-FDG or Na(124)I
      ((124)I). These calibrated S/B-threshold-volume curves were used in estimating
      the volume by applying an iterative procedure. The ITM was validated with a PET
      phantom containing spheres and with 39 PET tumors that were discernable on CT by
      using whole-body (18)F-FDG (15 patients) and (124)I PET/CT (9 patients): The
      measured S/B ratios of the lesions were estimated from PET images, and their
      volumes were iteratively calculated using the calibrated S/B-threshold-volume
      curves. The resulting PET volumes were then compared with the known sphere inner
      volume and CT volumes of tumors that served as gold standards. RESULTS: Phantom
      data analysis showed that the S/B-threshold-volume curves of (18)F-FDG and (124)I
      were similar. The average absolute deviation (expressed as a percentage of the
      expected volume) obtained in the PET validation phantom was 10% for volumes
      larger than 1.0 mL; sphere volumes of 0.5 mL showed a significantly larger
      deviation. For patients, the average absolute deviation for volumes between 0.8
      and 7.5 mL was about 9% (31 lesions), whereas volumes larger than 7.5 mL showed
      an average volume mismatch of 15% (8 lesions). CONCLUSION: The ITM sufficiently
      estimated the clinical volumes in the range of 0.8-7.5 mL; volumes larger than
      7.5 mL showed greater deviations that were still acceptable. These findings are
      associated with the limitation of the ITM. The ITM is especially useful for
      lesions that are only visible on PET. As a consequence, the lesion dosimetry is
      feasible with sufficient accuracy using PET images only.

PMID- 17204707
TI  - Fabrication and characterization of a 0.5-mm lutetium oxyorthosilicate detector
      array for high-resolution PET applications.
AB  - With the increasing use of in vivo imaging in mouse models of disease, there are
      many interesting applications that demand imaging of organs and tissues with
      submillimeter resolution. Though there are other contributing factors, the
      spatial resolution in small-animal PET is still largely determined by the
      detector pixel dimensions. METHODS: In this work, a pair of lutetium
      oxyorthosilicate (LSO) arrays with 0.5-mm pixels was coupled to multichannel
      photomultiplier tubes and evaluated for use as high-resolution PET detectors.
      RESULTS: Flood histograms demonstrated that most crystals were clearly
      identifiable. Energy resolution varied from 22% to 38%. The coincidence timing
      resolution was 1.42-ns full width at half maximum (FWHM). The intrinsic spatial
      resolution was 0.68-mm FWHM as measured with a 30-gauge needle filled with (18)F.
      The improvement in spatial resolution in a tomographic setting is demonstrated
      using images of a line source phantom reconstructed with filtered backprojection
      and compared with images obtained from 2 dedicated small-animal PET scanners.
      Finally, a projection image of the mouse foot is shown to demonstrate the
      application of these 0.5-mm LSO detectors to a biologic task. CONCLUSION: A pair
      of highly pixelated LSO detections has been constructed and characterized for use
      as high-spatial-resolution PET detectors. It appears that small-animal PET
      systems capable of a FWHM spatial resolution of 600 microm or less are feasible
      and should be pursued.

PMID- 17204708
TI  - Therapeutic effects of a 186Re-complex-conjugated bisphosphonate for the
      palliation of metastatic bone pain in an animal model.
AB  - Previously, based on the concept of bifunctional radiopharmaceuticals, we
      developed a highly stable (186)Re-mercaptoacetylglycylglycylglycine (MAG3)
      complex-conjugated bisphosphonate, [[[[(4-hydroxy-4,4
      diphosphonobutyl)carbamoylmethyl]carbamoylmethyl]carbamoylmethyl]carbamoylmethane
      hiolate] oxorhenium(V) ((186)Re-MAG3-HBP), for the treatment of painful bone
      metastases. This agent showed a superior biodistribution as a bone-seeking agent
      in normal mice when compared with (186)Re-1-hydroxyethylidene-1,1-diphosphonate
      ((186)Re-HEDP). In this study, we evaluated the therapeutic effects of (186)Re
      MAG3-HBP using an animal model of bone metastasis. METHODS: The model was
      prepared by injecting syngeneic MRMT-1 mammary tumor cells into the left tibia of
      female Sprague-Dawley rats. (186)Re-MAG3-HBP (55.5, 111, or 222 MBq/kg) or
      (186)Re-HEDP (55.5 MBq/kg) was then administered intravenously 21 d later. To
      evaluate the therapeutic effects and side effects, tumor size and peripheral
      blood cell counts were determined. Palliation of bone pain was evaluated by a von
      Frey filament test. RESULTS: In the rats treated with (186)Re-HEDP, tumor growth
      was comparable with that in untreated rats. In contrast, when (186)Re-MAG3-HBP
      was administered, tumor growth was significantly inhibited. Allodynia induced by
      bone metastasis was attenuated by treatment with (186)Re-MAG3-HBP or (186)Re
      HEDP, but (186)Re-MAG3-HBP tended to be more effective. CONCLUSION: These results
      indicate that (186)Re-MAG3-HBP could be useful as a therapeutic agent for the
      palliation of metastatic bone pain.

PMID- 17204709
TI  - Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in
      humans.
AB  - We investigated the biodistribution and radiation dosimetry of the PET amyloid
      imaging agent (11)C-PIB ((11)C-6-OH-BTA-1) (where BTA is benzothiazole) in
      humans. Previous radiation exposure estimates have been based on animal
      experiments. A dosimetry study in humans is essential for a balanced risk-benefit
      assessment of (11)C-PIB PET studies. METHODS: We used data from 16 different
      (11)C-PIB PET scans on healthy volunteers to estimate radiation exposure. Six of
      these scans were dynamic imaging over the abdominal region: 3 covering the upper
      abdomen and 3 covering the middle abdomen. On average, 489 MBq of (11)C-PIB
      (range, 416-606 MBq) were injected intravenously, and dynamic emission scans were
      recorded for up to 40 min. Two subjects had whole-body imaging over the entire
      body to illustrate the biodistribution. PET brain scans and blood and urine
      radioactivity measurements from our previous (11)C-PIB studies were also
      analyzed. Thirteen source organs and the remainder of the body were studied to
      estimate residence times and mean radiation-absorbed doses. The MIRD method was
      used to calculate the radiation exposure of selected target organs and the body
      as a whole. RESULTS: There is a high degree of consistency between our human data
      and previous biodistribution information based on baboons. In our study, the
      highest radiation-absorbed doses were received by the gallbladder wall (41.5
      microGy/MBq), liver (19.0 microGy/MBq), urinary bladder wall (16.6 microGy/MBq),
      kidneys (12.6 microGy/MBq), and upper large intestine wall (9.0 microGy/MBq). The
      hepatobiliary and renal systems were the major routes of clearance and excretion,
      with approximately 20% of the injected radioactivity being excreted into urine.
      The effective radiation dose was 4.74 microSv/MBq. CONCLUSION: The established
      clinical dose of (11)C-PIB required for 3-dimensional PET amyloid imaging has an
      acceptable effective radiation dose. This dose is comparable with the average
      exposure expected in other PET brain receptor tracer studies. (11)C-PIB is
      rapidly cleared from the body, largely by the kidneys. From the viewpoint of
      radiation safety, these results support the use of (11)C-PIB in clinical PET
      studies.

PMID- 17204710
TI  - Radiation dose distribution in human kidneys by octreotides in peptide receptor
      radionuclide therapy.
AB  - Ex vivo autoradiographs of healthy kidney tissue from patients who received
      (111)In-DTPA-octreotide (DTPA is diethylenetriaminepentaacetic acid) before
      nephrectomy showed very heterogeneous radioactivity patterns in the kidneys. The
      consequences of the reported inhomogeneities have been evaluated for radionuclide
      therapy with (90)Y- DOTA-Tyr(3)-octreotide (DOTA is 1,4,7,10
      tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid), (177)Lu-DOTA-Tyr(3)
      octreotate, and (111)In-DTPA-octreotide by calculating dose distributions and
      dose-volume histograms (DVHs) for the kidneys. METHODS: Monte Carlo radiation
      transport calculations were performed by using the MCNP code version 5. The
      autoradiography data were used in a 2-dimensional model of the kidney tissue
      sections. A voxel structure inside the MIRD Pamphlet 19 multiregion kidney model
      was developed to generate a 3-dimensional representation of the autoradiographs.
      Dose distributions were calculated for the beta-emitter (90)Y, the low-energy
      electron and gamma-emitter (111)In, and the beta- and gamma-emitter (177)Lu.
      Isodose curves were generated for the 2-dimensional kidney sections and DVHs for
      the 3-dimensional kidney model. RESULTS: The isodose curves for the high-energy
      beta-emitter (90)Y did not show a sign of the inhomogeneous activity
      distribution, apart from the cortex-medulla boundaries. Both (111)In and (177)Lu
      isodose curves follow the autoradiographic activity distribution exactly. The 2
      gamma-rays from (111)In give higher doses to the low-radioactivity regions in the
      kidney sections. The DVHs show that the inhomogeneous activity distribution
      creates considerable volumes within the kidney and within the cortex with lower
      doses than the average kidney dose, together with volumes receiving much higher
      doses. This effect is most profound for (177)Lu, but also (111)In shows this
      heterogeneity in the dose distribution. CONCLUSION: Kidney dosimetry for
      radionuclide therapy can be based on average MIRD-based dose models for high
      energy beta-emitters (such as (90)Y). In contrast, low-energy beta-emitters (such
      as (177)Lu) and Auger-electron-emitting radionuclides (such as (111)In) produce
      dose distributions in the kidneys that are very dependent on the activity
      distribution pattern in the kidney or renal cortex. Complication probability
      models for renal tissue damage after radionuclide therapy with these latter
      nuclides need to be developed, as the existing models based on average dose to
      the kidney or cortex from external beam therapy experience are most probably not
      valid.

PMID- 17204711
TI  - Prediction of absorbed dose to normal organs in thyroid cancer patients treated
      with 131I by use of 124I PET and 3-dimensional internal dosimetry software.
AB  - The objective of this work was to determine normal organ (131)I dosimetry in
      patients undergoing radioiodide therapy for thyroid cancer by use of serial
      scanning with (124)I PET. METHODS: A total of 26 patients who had papillary and
      follicular metastatic thyroid cancer and who were already enrolled in a Memorial
      Sloan-Kettering Cancer Center (131)I thyroid cancer protocol were selected for
      this study. Imaging before (131)I therapy consisted of multiple, whole-body
      (124)I PET studies over a period of 2-8 d, an (18)F-FDG PET scan and, for some, a
      diagnostic CT scan. With a set of in-house-developed software tools (3
      dimensional internal dosimetry [3D-ID] and Multiple Image Analysis Utility
      [MIAU]), the following procedures were performed: all PET emission and
      transmission and CT image sets were aligned; half-life-corrected tomographic
      images of (131)I activity were integrated voxel by voxel to produce cumulated
      (131)I activity images; and the latter images were, in turn, convolved with a
      (131)I electron-photon point kernel to produce images of (131)I dose
      distribution. Cumulated activity values and calculated residence times obtained
      from our patient-specific dosimetry software (3D-ID) were used as inputs to
      OLINDA, and volume difference-adjusted comparisons were made between the mean
      dose estimates. RESULTS: With 3D-ID, dose volume histograms and mean doses were
      calculated for 14 organs, and results were expressed in Gy/GBq. The highest mean
      dose, 0.26 Gy/GBq, was seen in the right submandibular gland, whereas the lowest
      mean dose, 0.029 Gy/GBq, was seen in the brain. CONCLUSION: This is the first
      comprehensive study of normal organ dosimetry in patients by use of a
      quantitative tomographic imaging modality.

PMID- 17204713
TI  - Reference and target region modeling of [11C]-(R)-PK11195 brain studies.
AB  - PET with [(11)C]-(R)-PK11195 is currently the modality of choice for the in vivo
      imaging of microglial activation in the human brain. In this work we devised a
      supervised clustering procedure and a new quantification methodology capable of
      producing binding potential (BP) estimates quantitatively comparable with those
      derived from plasma input with robust quantitative implementation at the pixel
      level. METHODS: The new methodology uses predefined kinetic classes to extract a
      gray matter reference tissue without specific tracer binding and devoid of
      spurious signals (in particular, blood pool and muscle). Kinetic classes were
      derived from an historical database of 12 healthy control subjects and from 3
      patients with Huntington's disease. BP estimates were obtained using rank-shaping
      exponential spectral analysis (RS-ESA) (both plasma and reference input) and the
      simplified reference tissue model (SRTM). Comparison between plasma- derived BPs
      and those produced with the new reference methodology was performed using 6
      additional healthy control subjects. Reliability of the new methodology was
      performed on 4 test-retest studies of patients with Alzheimer's disease. RESULTS:
      The new algorithm selected reference voxels in gray matter tissue avoiding
      regions with specific binding located, in particular, in the venous and arterial
      circulation. Using the new reference, BP values obtained using a plasma input and
      a reference input were in excellent agreement and highly correlated (r = 0.811, P
      < 10(-5)) when calculated with RS-ESA and less so (r = 0.507, P < 0.005) when
      SRTM was used. In the production of parametric maps, SRTM was used with the new
      reference extraction, resulting in test-retest variability (10.6%; mean ICC =
      0.878) that was superior to that obtained using the previous unsupervised
      clustering approach (mean ICC = 0.596). CONCLUSION: Reference region modeling
      combined with supervised reference tissue extraction produces a robust and
      reproducible quantitative assessment of [(11)C]-(R)-PK11195 studies in the human
      brain.

PMID- 17204712
TI  - Therapeutic potential of 90Y- and 131I-labeled anti-CD20 monoclonal antibody in
      treating non-Hodgkin's lymphoma with pulmonary involvement: a Monte Carlo-based
      dosimetric analysis.
AB  - Pulmonary involvement is common in patients with non-Hodgkin's lymphoma (NHL).
      (90)Y- and (131)I-anti-CD20 antibodies (ibritumomab tiuxetan and tositumomab,
      respectively) have been approved for the treatment of refractory low-grade
      follicular NHL. In this work, we used Monte Carlo-based dosimetry to compare the
      potential of (90)Y and (131)I, based purely on their emission properties, in
      targeted therapy for NHL lung metastases of various nodule sizes and tumor
      burdens. METHODS: Lung metastases were simulated as spheres, with radii ranging
      from 0.2 to 5.0 cm, which were randomly distributed in a voxelized adult male
      lung phantom. Total tumor burden was varied from 0.2 to 1,641 g. Tumor uptake and
      retention kinetics of the 2 radionuclides were assumed equivalent; a uniform
      distribution of activity within tumors was assumed. Absorbed dose to tumors and
      lung parenchyma per unit activity in lung tumors was calculated by a Monte Carlo
      based system using the MCNP4B package. Therapeutic efficacy was defined as the
      ratio of mean absorbed dose in the tumor to that in normal lung. Dosimetric
      analysis was also performed for a lung-surface distribution of tumor nodules
      mimicking pleural metastatic disease. RESULTS: The therapeutic efficacy of both
      (90)Y and (131)I declined with increasing tumor burden. In treating tumors with
      radii less than 2.0 cm, (131)I targeting was more efficacious than (90)Y
      targeting. (90)Y yielded a broader distribution of tumor absorbed doses, with the
      minimum 54.1% lower than the average dose; for (131)I, the minimum absorbed dose
      was 33.3% lower than the average. The absorbed dose to normal lungs was reduced
      when the tumors were distributed on the lung surface. For surface tumors, the
      reductions in normal-lung absorbed dose were greater for (90)Y than for (131)I,
      but (131)I continued to provide a greater therapeutic ratio across different
      tumor burdens and sizes. CONCLUSION: Monte Carlo-based dosimetry was performed to
      compare the therapeutic potential of (90)Y and (131)I targeting of lung
      metastases in NHL patients. (131)I provided a therapeutic advantage over (90)Y,
      especially in tumors with radii less than 2.0 cm and at lower tumor burdens. For
      both (90)Y- and (131)I-labeled antibodies, treatment is more efficacious when
      applied to metastatic NHL cases with lower tumor burdens. (131)I has advantages
      over (90)Y in treating smaller lung metastases.

PMID- 17204714
TI  - PET/CT in cancer patient management. Commentary.

PMID- 17204715
TI  - PET/CT in cancer patient management. Introduction.

PMID- 17204716
TI  - Screening for cancer with PET and PET/CT: potential and limitations.
AB  - Screening for cancer remains a very emotional and hotly debated issue in
      contemporary medical practice. An analysis of published data reveals a multitude
      of opinions based on a limited amount of reliable data. Even for breast cancer
      screening, which is now widely practiced in the United States and many European
      countries, there is continuing controversy regarding the appropriate age limits
      for screening mammography and, in fact, concerning the value of mammography
      itself. Similarly, there is no agreement as to whether screening for lung or
      prostate cancer is meaningful as currently practiced. Recommendations and
      decisions regarding cancer screening should be based on reliable data, not good
      intention, assumptions, or speculation. Therefore, we first explain the
      underlying principles and premises of screening and then briefly discuss current
      controversies regarding screening for breast, prostate, and lung cancers.
      Recently, some authors advocated CT, PET, or PET/CT for whole-body screening
      without support from reliable data. We discuss the potential financial, legal,
      and radiation safety implications associated with whole-body CT or PET cancer
      screening. We conclude from the available data that neither CT nor PET/CT cancer
      screening is currently warranted. Far from providing a desirable binary answer
      (presence of absence of cancer), in nonselected populations the procedures
      frequently yield equivocal or indeterminate findings that require further
      evaluation, with associated costs and potential complications. The clinical and
      statistical relevance of occasionally detected cancers is likely too low to
      justify population-wide screening efforts with these 2 imaging modalities.
      Ultimately, the true utility, or lack thereof, of PET and PET/CT for cancer
      screening can be assessed only in a prospective randomized trial. Because of
      prohibitive costs and the required length of follow-up, it is unlikely that such
      a trial will ever be conducted. Rather than spending time and resources on
      screening studies, medical practitioners should continue using whole-body PET/CT
      for diagnosing, staging, and restaging cancer and for monitoring treatment
      effects. Researchers should also investigate the utility of whole-body PET/CT for
      the surveillance of selected groups of patients who have cancer, who have
      completed curative treatment, but who remain at high risk for recurrent disease.

PMID- 17204717
TI  - Integrating PET and PET/CT into the risk-adapted therapy of lymphoma.
AB  - Imaging with 18F-FDG PET is increasingly accepted as a valuable tool for lymphoma
      management. A recent shift in the use of PET and PET/CT in medical practice has
      become evident. We selected aggressive lymphomas as a platform for the discussion
      of these imaging modalities in oncology patients and the resulting management
      questions. METHODS: On the basis of our clinical experience and a review of the
      literature, we evaluated the emerging role of 18F-FDG PET in staging, response
      assessment, risk stratification, and tailored therapy. We explored the biologic
      meaning of true-positive or true-negative PET results in assessing tumor killing
      and the implications for risk-adapted therapy of lymphoma. RESULTS: PET/CT
      improves the accuracy of staging and response assessment over that of
      conventional anatomic imaging. The strong prognostic value of PET for aggressive
      lymphomas is established, whether the imaging is performed at the end of therapy
      or after only a few cycles of chemotherapy. How to modify therapy on the basis of
      PET results is not yet established, although it is clear that high-risk patient
      subsets can be reliably identified. CONCLUSION: PET/CT improves the accuracy of
      staging and response assessment over that of CT alone. A negative midtreatment
      PET result does not indicate the absence of a viable tumor or that therapy can be
      abbreviated or reduced in intensity. Similarly, a positive PET result does not
      necessarily indicate a viable tumor or that extending or intensifying treatment
      will benefit the patient. In assessing response, it is possible that prognosis
      rests not only on whether the PET result is positive or negative but also on the
      intensity of the signal. Although the prognostic value of PET for lymphoma is now
      clear, how to tailor therapy accordingly is a separate matter that requires
      further investigation.

PMID- 17204718
TI  - Early detection of cancer recurrence: 18F-FDG PET/CT can make a difference in
      diagnosis and patient care.
AB  - Early detection of recurrence is clinically important and can improve the
      prognosis and survival of patients with cancer. CT, considered the primary method
      of investigation because of its low cost and widespread availability, provides
      high-resolution anatomic details but may underestimate the actual tumor burden by
      overlooking small tumor clusters in areas of distorted anatomy after treatment.
      18F-FDG PET is an effective whole-body imaging technique that detects metabolic
      changes preceding structural findings. However, the specificity of PET is
      impaired by false-positive or equivocal results attributable to the lack of
      precise anatomic landmarks and to sites of increased 18F-FDG uptake of
      nonmalignant etiology. PET/CT provides fused images that demonstrate the
      complementary roles of functional and anatomic assessments in the diagnosis of
      cancer recurrence through the precise localization of suspected 18F-FDG foci and
      their characterization as malignant or benign. In addition to the accurate
      diagnosis and definition of the whole extent of recurrent cancer, PET/CT has an
      impact on patient management because it can assist in defining potential
      candidates for surgery for cure, planning the appropriate surgical or
      radiotherapy approach, and referring patients with unresectable disease to other
      therapeutic options.

PMID- 17204719
TI  - Monitoring cancer treatment with PET/CT: does it make a difference?
AB  - PET with the glucose analog 18F-FDG is increasingly being used to monitor the
      effectiveness of therapy in patients with malignant lymphomas and a variety of
      solid tumors. The use of integrated PET/CT instead of stand-alone PET for
      treatment monitoring poses some methodologic challenges for the quantitative
      analysis of PET scans but also provides the opportunity to integrate morphologic
      information and functional information. This integration may allow the definition
      of new parameters for assessment of the tumor response and will also facilitate
      the use of PET in research studies as well as in clinical practice. This review
      addresses how CT-based attenuation correction may affect the quantitative
      analysis of 18F-FDG PET scans and summarizes the results of recent studies with
      PET/CT for treatment monitoring for lung cancer and gastrointestinal stromal
      tumors. The review concludes with an outlook on how PET/CT could make a
      difference in drug development and clinical management for patients.

PMID- 17204720
TI  - Can PET/CT replace separate diagnostic CT for cancer imaging? Optimizing CT
      protocols for imaging cancers of the chest and abdomen.
AB  - Stage-adapted treatment in oncology relies on correct tumor staging for patients
      with malignant diseases. To ensure accurate assessment of the tumor stage in
      thoracic and abdominal diseases by PET/CT, both CT and PET need to be optimized.
      In this setting, different malignant diseases require customized imaging
      protocols. Although in the clinical setting of therapy assessment, PET/CT with
      integration of low-dose, nonenhanced CT may be sufficient, tumor staging may
      require a more sophisticated CT protocol. This review focuses on potential CT
      protocols for imaging cancers of the chest and abdomen. Examples of CT protocols
      are presented and discussed for non-small cell lung cancer, breast cancer,
      colorectal cancer, gastrointestinal stromal tumors, and interventional liver
      therapy.

PMID- 17204721
TI  - Clinical role of 18F-FDG PET/CT in the management of squamous cell carcinoma of
      the head and neck and thyroid carcinoma.
AB  - 18F-FDG PET/CT has rapidly become a widely used imaging modality for evaluating a
      variety of malignancies, including squamous cell carcinoma of the head and neck
      and thyroid cancer. Using both published data and the multidisciplinary
      experience at our institution, we provide a practical set of guidelines and
      algorithms for the use of 18F-FDG PET/CT in the evaluation and management of head
      and neck cancer and thyroid cancer.

PMID- 17204722
TI  - PET-based treatment planning in radiotherapy: a new standard?
AB  - Molecular imaging, in particular, PET, has brought an additional dimension to
      management for patients with cancer. 18F-FDG, which is the most widely available
      tracer, has been shown to be of value for the selection of target volumes in
      radiation oncology. Depending on its sensitivity and specificity, 18F-FDG has
      been shown to influence the selection of target volumes for non-small cell lung
      cancers (NSCLC) or for esophageal tumors. On the other hand, for tumors such as
      head and neck squamous cell carcinomas (HNSCC) and rectal carcinomas, convincing
      data on the value of 18F-FDG for target volume selection are still lacking. For
      target volume delineation, given that an adequate method is used for volume
      segmentation, the added value of 18F-FDG has been demonstrated for HNSCC and
      NSCLC. For both types of tumors, modifications in target volume delineation
      translated into differences in dose distribution compared with the results of CT
      scan-based plans. Studies are in progress for rectal tumors. Novel markers of
      tumor hypoxia or proliferation have the potential to modify the delineation of
      target volumes, allowing for "dose painting" in selected subvolumes. Finally,
      variations in tumor volume and viability during radiotherapy also are under
      intense investigation, potentially paving the way for so-called "theragnostic" or
      adaptive dose distribution during treatment. This review discusses how PET/CT
      might modify the current state of the art of radiotherapy planning.

PMID- 17204723
TI  - Improvements in cancer staging with PET/CT: literature-based evidence as of
      September 2006.
AB  - PET/CT with 18F-FDG is increasingly being used for staging, restaging, and
      treatment monitoring for cancer patients. CT is still frequently used only for
      attenuation correction and lesion localization. However, increasing sales of high
      end scanners that combine PET with 64-detector CT strongly suggest that the field
      is moving toward a comprehensive concept, whereby diagnostic CT studies during
      intravenous contrast material application are combined with the highest-quality
      PET studies. At many institutions, in-line PET/CT has replaced separately
      acquired PET and CT examinations for many oncologic indications. This replacement
      has occurred despite the fact that only a relatively small number of well
      designed prospective studies have verified imaging findings against the gold
      standard of histopathologic tissue evaluation. However, a large number of studies
      have used acceptable reference standards, such as pathology, imaging, and other
      clinical follow-up findings, for validating PET/CT findings. From these data, we
      believe, has emerged reliable evidence in support of the notion that PET/CT
      offers diagnostic advantages over its individual components for the major
      cancers.

PMID- 17204724
TI  - Effects of the Irish smoking ban on respiratory health of bar workers and air
      quality in Dublin pubs.
AB  - BACKGROUND: Environmental tobacco smoke (ETS) causes disease in nonsmokers.
      Workplace bans on smoking are interventions to reduce exposure to ETS to try to
      prevent harmful health effects. On March 29, 2004, the Irish government
      introduced the first national comprehensive legislation banning smoking in all
      workplaces, including bars and restaurants. This study examines the impact of
      this legislation on air quality in pubs and on respiratory health effects in bar
      workers in Dublin. METHODS: Exposure study. Concentrations of particulate matter
      2.5 microm or smaller (PM(2.5)) and particulate matter 10 microm or smaller
      (PM(10)) in 42 pubs were measured and compared before and after the ban. Benzene
      concentrations were also measured in 26 of the pubs. Health effects study. Eighty
      one barmen volunteered to have full pulmonary function studies, exhaled breath
      carbon monoxide, and salivary cotinine levels performed before the ban and
      repeated 1 year after the ban. They also completed questionnaires on exposure to
      ETS and respiratory symptoms on both occasions. FINDINGS: Exposure study. There
      was an 83% reduction in PM(2.5) and an 80.2% reduction in benzene concentration
      in the bars. Health effects study. There was a 79% reduction in exhaled breath
      carbon monoxide and an 81% reduction in salivary cotinine. There were
      statistically significant improvements in measured pulmonary function tests and
      significant reductions in self-reported symptoms and exposure levels in
      nonsmoking barmen volunteers after the ban. CONCLUSIONS: A total workplace
      smoking ban results in a significant reduction in air pollution in pubs and an
      improvement in respiratory health in barmen.

PMID- 17204725
TI  - Smoking affects response to inhaled corticosteroids or leukotriene receptor
      antagonists in asthma.
AB  - RATIONALE: One-quarter to one-third of individuals with asthma smoke, which may
      affect response to therapy and contribute to poor asthma control. OBJECTIVES: To
      determine if the response to an inhaled corticosteroid or a leukotriene receptor
      antagonist is attenuated in individuals with asthma who smoke. METHODS: In a
      multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44
      nonsmokers and 39 light smokers with mild asthma were assigned randomly to
      treatment twice daily with inhaled beclomethasone and once daily with oral
      montelukast. MEASUREMENTS AND MAIN RESULTS: Primary outcome was change in
      prebronchodilator FEV(1) in smokers versus nonsmokers. Secondary outcomes
      included peak flow, PC(20) methacholine, symptoms, quality of life, and markers
      of airway inflammation. Despite similar FEV(1), bronchodilator response, and
      sensitivity to methacholine at baseline, subjects with asthma who smoked had
      significantly more symptoms, worse quality of life, and lower daily peak flow
      than nonsmokers. Adherence to therapy did not differ significantly between
      smokers and nonsmokers, or between treatment arms. Beclomethasone significantly
      reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers
      and nonsmokers, but increased FEV(1) (170 ml, p = 0.0003) only in nonsmokers.
      Montelukast significantly increased a.m. peak flow in smokers (12.6 L/min, p =
      0.002), but not in nonsmokers. CONCLUSIONS: In subjects with mild asthma who
      smoke, the response to inhaled corticosteroids is attenuated, suggesting that
      adjustments to standard therapy may be required to attain asthma control. The
      greater improvement seen in some outcomes in smokers treated with montelukast
      suggests that leukotrienes may be important in this setting. Larger prospective
      studies are required to determine whether leukotriene modifiers can be
      recommended for managing asthma in patients who smoke.

PMID- 17204726
TI  - Oral treatment with live Lactobacillus reuteri inhibits the allergic airway
      response in mice.
AB  - RATIONALE: Clinical trials have demonstrated that probiotics may be effective in
      the treatment and prevention of atopic disease in children but there have been
      few reports of therapeutic effects of oral probiotics outside the
      gastrointestinal tract. OBJECTIVES: We investigated the effect of two probiotic
      organisms on the response to antigen challenge in a mouse model of allergic
      airway inflammation. METHODS: We used an ovalbumin-sensitized asthma model in
      BALB/c and Toll-like receptor 9-deficient mice. Animals were treated with
      probiotic organisms via gavaging needle before antigen challenge. After antigen
      challenge, airway responsiveness to methacholine, influx of inflammatory cells to
      the lung, and cytokine levels in bronchoalveolar lavage fluid were assessed.
      RESULTS: Oral treatment with live Lactobacillus reuteri but not Lactobacillus
      salivarius significantly attenuated the influx of eosinophils to the airway lumen
      and parenchyma and reduced the levels of tumor necrosis factor, monocyte
      chemoattractant protein-1, IL-5, and IL-13 in bronchoalveolar lavage fluid of
      antigen-challenged animals, but there was no change in eotaxin or IL-10. L.
      reuteri but not L. salivarius also decreased allergen-induced airway
      hyperresponsiveness. These responses were dependent on Toll-like receptor 9 and
      were associated with increased activity of indoleamine 2,3-dioxygenase. Killed
      organisms did not mimic the ability of the live L. reuteri to attenuate
      inflammation or airway hyperresponsiveness. CONCLUSION: Oral treatment with live
      L. reuteri can attenuate major characteristics of an asthmatic response in a
      mouse model of allergic airway inflammation. These results suggest that oral
      treatment with specific live probiotic strains may have therapeutic potential in
      the treatment of allergic airway disease.

PMID- 17204727
TI  - Secreted modular calcium-binding protein 2 haplotypes are associated with
      pulmonary function.
AB  - RATIONALE: Previously reported linkage to FEV(1) (LOD score = 5.0) on 6q27 in the
      Framingham Heart Study (FHS) led us to explore a candidate gene, SMOC2, at 168.6
      Mb. OBJECTIVES: We tested association between SMOC2 polymorphisms and FEV(1) and
      FVC in unrelated FHS participants. METHODS: Twenty single-nucleotide
      polymorphisms (SNPs) around SMOC2 were genotyped in 1,734 subjects. MEASUREMENTS
      AND MAIN RESULTS: SNP data were analyzed using multiple linear regression models
      incorporating sex, age, body mass index, height, and smoking history as
      covariates, and analyses were repeated within strata of ever- and never-smokers.
      The minor allele of SNP rs1402 was associated with higher mean FEV(1) (p = 0.003)
      and FVC (p = 0.02) measures. In never-smoking subjects, association with higher
      measures was observed with the minor allele of rs747995 (FEV(1), p = 0.0006; FVC,
      p = 0.0008). These two SNPs lie in different haplotype blocks and reside in
      intron 4 of SMOC2. Haplotype analysis revealed a common G-T haplotype (rs747995
      rs1402) with 77% frequency in never-smoking FHS subjects. The G-T haplotype was
      associated with reduction of 126 ml for FEV(1) (p = 0.0002) and 157 ml for FVC (p
      = 0.0002). The G-T haplotype was similarly associated in a set of never-smoking
      subjects from the Family Heart Study (FEV(1), p = 0.03; FVC, p = 0.03).
      CONCLUSIONS: The replication of the association in two populations supports the
      possibility that SMOC2 might play an important role in the determination of
      FEV(1) and FVC.

PMID- 17204728
TI  - Measuring performance in primary care: what patient outcome indicators do
      physicians value?
AB  - BACKGROUND: Determining which patient outcome indicators may be appropriate to
      include in a primary care, practice performance tool is a difficult task.
      Unfortunately, no published studies currently document the opinions of these
      physicians regarding which indicators they most value. OBJECTIVE: To ascertain
      the level of agreement among primary care physicians regarding the most salient
      patient outcome indicators for measuring performance in primary care. METHODS: A
      random population survey of 115 adult primary care physicians. The survey
      consisted of a comprehensive list of health characteristics included in 8
      validated instruments (eg, SF-36, Sickness Impact Profile), as well as 10 common
      clinical indicators and 6 health behaviors. Each item was ranked using a 5-point
      Likert scale regarding its value for inclusion in a performance measure. RESULTS:
      Analysis of 93 returned surveys (RR 81%) indicated strong agreement (> or = 75%)
      that 19 health characteristics were important or very important. These
      characteristics fit into 8 domains: physical functioning, psychological
      functioning, social functioning, pain, quality of life, physiologic symptoms,
      health behaviors, and clinical indicators. Notably absent were measures of social
      support and health perceptions. CONCLUSIONS: Strong agreement exists among
      practicing primary care physicians regarding the most valued patient outcome
      indicators. Development of practice performance measures should be influenced by
      such data.

PMID- 17204729
TI  - Adult fat intake associated with the presence of children in households: findings
      from NHANES III.
AB  - BACKGROUND: Increasing prevalence of obesity and lifestyle related chronic
      disease is fundamentally tied to Americans' poor eating habits. Family
      environment, including the presence of children, may affect adults' diet
      behavior. OBJECTIVE: To compare dietary fat intake between adults with and
      without minor children in the home. DESIGN: Secondary analysis of cross-sectional
      survey data from the National Health and Nutrition Examination Survey III (NHANES
      III) public use dataset. SUBJECTS: Adults aged 17 to 65 years with and without
      children younger than 17 years old in the home. OUTCOME VARIABLES: Intake of
      total fat, saturated fat, and kilocalories based on a 24-hour dietary recall and
      a selection of high-fat foods from a food frequency questionnaire. METHODS:
      Linear and logistic regression, accounting for the sample weights and complex
      survey design. RESULTS: The presence of children in the household was associated
      with significantly higher adjusted total fat consumption for adults (4.9 g/24
      hours [95% CI: 0.8, 9.1]) and significantly higher adjusted saturated fat
      consumption (1.7 g/24 hours [0.3, 3.3]). Adults with children ate many high-fat
      foods more frequently than adults without children, including salty snacks,
      pizza, cheese, beef, ice cream, cakes/cookies, bacon/sausage/processed meats, and
      peanuts. CONCLUSIONS: The presence of children in the home may affect adults'
      diets. Providers should emphasize dietary discretion for the entire family.

PMID- 17204730
TI  - Three measures of sleep, sleepiness, and sleep deprivation and the risk of
      injury: a case-control and case-crossover study.
AB  - PURPOSE: Sleepiness and sleep deprivation are associated with injury, but few
      case-control studies have addressed them. We sought to add to the body of
      analytic observational studies. METHODS: Case-control and case-crossover study of
      2517 injured patients interviewed in person in 3 emergency departments and
      matched by age, sex, rural versus urban, day of week, and hour of day with 1856
      controls. Sleep constructs were measured by the following: (1) self-perceived
      sleepiness at injury or matched control time using 3 adjectives (tired, sleepy,
      drowsy); (2) usual sleep quality and quantity, and differences in those in the
      past 7 days; and (3) hours of sleep in the 24 hours before injury and the 24
      hours before that. RESULTS: Better sleep quality in the past 7 days was
      associated with a lower risk of injury (odds ratio (OR) 0.88, 95% confidence
      interval (CI) 0.80 to 0.97). Self-reported sleepiness just before injury compared
      with control time was associated with a lower risk of injury, with ORs of 0.82
      per unit on a 0-to-12 scale (95% CI 0.78 to 0.86) in case-control analysis and
      0.76 (0.73 to 0.80) in case-crossover analysis. In case-crossover analysis,
      additional sleep in the 24 hours before injury compared with the 24 hours before
      that was associated with an increased risk of injury (OR 1.06 per hour, 95% CI
      1.03 to 1.09), but this effect disappeared when we controlled for activity,
      location, and recent alcohol consumption. CONCLUSIONS: Better recent sleep
      quality was associated with a lower risk of injury, but surprisingly, feeling
      sleepy was also.

PMID- 17204731
TI  - Does literacy education improve symptoms of depression and self-efficacy in
      individuals with low literacy and depressive symptoms? A preliminary
      investigation.
AB  - BACKGROUND AND OBJECTIVES: Individuals with low literacy and symptoms of
      depression have greater improvement of depression symptoms when their treatment
      includes education to enhance literacy skills. The reason why literacy
      enhancement helps depression symptoms is unknown, but we hypothesize that it
      might be due to improved self-efficacy. We studied whether providing literacy
      education to individuals with both depression symptoms and limited literacy might
      improve their self-efficacy. METHODS: We studied 39 individuals enrolled in an
      adult literacy program and who, on further testing with the Patient Health
      Questionnaire (PHQ-9) had symptoms of depression. While they participated in the
      literacy program, we monitored their self-efficacy using the General Self
      Efficacy (GSE) scale, and also monitored the severity of depression symptoms with
      the PHQ-9. Changes in GSE and PHQ-9 scores from baseline were assessed with the
      Wilcoxon Signed Ranks Test. RESULTS: Thirty-one (79.5%) subjects participated for
      1 year. There was a significant increase in their self-efficacy (P = .019) and a
      significant decrease in depression symptoms (P < .002). CONCLUSION: The results
      of this preliminary study suggest that among persons with low literacy and
      symptoms of depression, depression symptoms lessen as self-efficacy scores
      improve during participation in adult basic literacy education.

PMID- 17204732
TI  - A qualitative study of depression in primary care: missed opportunities for
      diagnosis and education.
AB  - PURPOSE: Depression is one of the most commonly encountered chronic conditions in
      primary care, yet it remains substantially underdiagnosed and undertreated. We
      sought to gain a better understanding of barriers to diagnosis of and entering
      treatment for depression in primary care. METHODS: We conducted and analyzed
      interviews with 15 subjects currently being treated for depression recruited from
      primary care clinics in an academic medical center and an academic public
      hospital. We asked about experiences with being diagnosed with depression and
      starting treatment, focusing on barriers to diagnosis, subject understanding of
      depression, and information issues related to treatment decisions. RESULTS:
      Subjects reported many visits to primary care practitioners without the question
      of depression being raised. The majority had recurrent depression. Many reported
      that they did not receive enough information about depression and its treatment
      options. In the majority of cases, practitioners decided the course of treatment
      with little input from the patients. CONCLUSIONS: In this sample of depressed
      patients, we found evidence of frequent missed diagnoses, substantial information
      gaps, and limited patient understanding and choice of treatment options. Quality
      improvement efforts should address not only screening and follow-up but patient
      education about depression and treatment options along with elicitation of
      treatment preferences.

PMID- 17204733
TI  - Effects of a couple communication program on marital adjustment.
AB  - BACKGROUND: Couples are usually advised to improve their communication skills to
      increase harmony and avoid conflicts. However, studies aimed at increasing
      marital adjustment in primary care are limited. METHODS: A Couple Communication
      Program was announced at the Ondokuz Mayis University Permanent Education Center,
      and the Dyadic Adjustment Scale was administered to 67 couples who volunteered.
      Twenty-eight persons (14 couples) with the lowest test scores were randomized
      into study and control groups. At the end of the program (post-test), the scale
      was again administered to the study group. Afterward, the pretest and post-test
      scores of the study and control groups were compared. The study group's pretest,
      post-test, and follow-up test scores were also examined. RESULTS: No difference
      in marital adjustment was found between the study and control groups before the
      start of the program (P > .05). The post-test scores of the couples attending the
      Couple Communication Program proved to be higher in total than the scores of
      those who did not attend (P < .001). The post-test and follow-up scores of the
      study group were significantly higher than their pretest scores (P < .001). There
      was no significant difference between the post-test and follow-up scores of the
      study group (P = 1.0). CONCLUSION: This program may have a positive effect on
      marital adjustment levels by improving communication skills and may lead to long
      term behavioral modifications in couples.

PMID- 17204734
TI  - The new "normal" blood pressure: what are the implications for family medicine?
AB  - BACKGROUND: In 2003, the Joint National Committee on Prevention, Detection,
      Evaluation, and Treatment of High Blood Pressure redefined normal blood pressure
      (BP) as less than 120/80 mm Hg and added the category of prehypertension,
      recommending that such patients receive counseling on lifestyle modifications.
      Based on population data, 41.8% of US adults have normal BP, 31% have
      prehypertension, and the remainder has hypertension. These percentages may not
      reflect the proportions seen in family medicine practices. The purposes of this
      study were to describe the proportion of adults in a family medicine practice
      with normal BP and the proportions with prehypertension and hypertension and to
      examine associations with having normal BP. METHODS: Records of 633 nonpregnant
      adults from a large family medicine clinic were reviewed for demographic and BP
      information. Proportions of subjects in each BP category (normal,
      prehypertension, or hypertension) were determined. Characteristics associated
      with normal BP were examined using chi(2) tests and logistic regression. RESULTS:
      Nearly 80% of adults in this population had prehypertension or hypertension.
      Subjects more likely to have normal BP were young, female, white, and not
      overweight/obese. Almost 60% of subjects had documented hypertension, were
      receiving antihypertensive medications, or had a BP on the day of visit > or =
      140/90 mm Hg. Over 20% had prehypertension. CONCLUSION: The proportion of adult
      family medicine patients with normal BP is low. Counseling 20% of adult patients
      about prehypertension while continuing to strive to improve BP control for the
      60% of patients with hypertension could pose a new challenge to clinicians
      working in family medicine offices.

PMID- 17204735
TI  - Family physicians expedite diagnosis of breast disease in urban minority women.
AB  - BACKGROUND: The specialty of a patient's usual provider of care is associated
      with use of mammography and stage of breast cancer diagnosis. It is unknown if
      specialty of usual provider of care affects time from discovery of a breast
      screening abnormality to diagnostic resolution. METHODS: Retrospective chart
      review study of 546 women who had breast biopsies at an urban public university
      hospital from 2001 to 2005. Time from abnormal mammogram or clinical breast
      examination to pathology report was compared by specialty of usual provider of
      care, sociodemographic, and clinical factors. Multivariate logistic regression
      was conducted to assess predictors of having diagnostic interval greater than 60
      days. RESULTS: The median diagnostic interval was 36 days (interquartile range 21
      to 63). After controlling for age, race, insurance, specialty of usual provider
      of care, employment status, and palpable lump, decreased odds of having
      diagnostic delay (over 60 days) included having a family physician (odds ratio
      (OR) 0.242; 95% confidence interval (CI), 0.09 to 0.69), private health insurance
      (OR 0.360; 95% CI, 0.15 to 0.89), and cancer diagnosis (OR 0.324; 95% CI, 0.17 to
      0.61). CONCLUSIONS: To improve timely follow-up of minority urban women with
      breast abnormalities, promoting development of a relationship with a family
      physician may be an important public health intervention.

PMID- 17204736
TI  - Utility of nerve conduction studies for carpal tunnel syndrome by family
      medicine, primary care, and internal medicine physicians.
AB  - INTRODUCTION: Nerve conduction studies (NCS) are increasingly being performed at
      the point-of-service by family medicine, primary care, and internal medicine
      (FM/PCP/IM) physicians. Carpal tunnel syndrome (CTS) is a common neuropathy often
      diagnosed with the aid of NCS. METHODS: A retrospective analysis of a point-of
      service NCS data registry was conducted; 1190 patients who underwent NCS by 613
      FM/PCP/IM physician practices, for evaluation of CTS were analyzed. Utility
      measures included demographic and electrophysiological characteristics of study
      population, adherence to evidence-based testing guidelines, and relevance of
      diagnostic outcomes. RESULTS: Tested patients tended to be over 40, female, and
      overweight or obese. The median nerve distal motor latency was 4.4 +/- 1.2 ms;
      92.6% of studies met the testing guideline; 30.5% of tested limbs yielded normal
      results; 53.1% CTS; 5.4% ulnar neuropathy; and 11.0% nonspecific upper extremity
      neuropathy. DISCUSSION: This study demonstrated that point-of-service NCS by
      FM/PCP/IM physicians for CTS was applied to appropriate patient subpopulations,
      was performed in accordance with evidence-based testing parameters, and generated
      relevant diagnostic outcomes.

PMID- 17204737
TI  - Transcranial Doppler: an introduction for primary care physicians.
AB  - Transcranial Doppler (TCD) is a diagnostic tool that can be used at bedside to
      assess the cerebral vasculature noninvasively. It is inexpensive, safe, and
      reliable when compared with other techniques. It can be repeated multiple times
      and can be used for continuous monitoring if needed. Screening of children with
      sickle cell disease to assess and prevent ischemic strokes and monitoring for
      vasospasm after subarachnoid hemorrhage are well established, evidenced based
      utilizations of TCD. It is useful for the evaluation of occlusive intracranial
      vascular lesions with many emerging indications in the management of ischemic
      stroke. TCD with micro-bubble enhancement has comparable sensitivity to
      transesophageal echocardiogram in detecting right-to-left atrial cardiac shunts.
      TCD is underused as a clinical tool despite well established indications. The
      pressure to contain increasing medical cost will likely result in increased
      utilization of this test in future.

PMID- 17204738
TI  - Persistence, adherence, and risk of discontinuation associated with commonly
      prescribed antihypertensive drug monotherapies.
AB  - OBJECTIVE: To assess 1-year persistence and adherence with monotherapy using the
      most commonly dispensed individual agent in 4 antihypertensive drug classes:
      hydrochlorothiazide (HCTZ), amlodipine, lisinopril, or valsartan. DESIGN:
      Retrospective, longitudinal analysis of initial prescriptions during 2001 to 2002
      from a nationwide administrative claims database representing 11 million covered
      lives in the United States. MEASUREMENTS: Drug utilization following initiation.
      Cox proportional hazards regression models controlled for demographics, case-mix,
      and concomitant treatments. RESULTS: Records for 60,685 subjects were included:
      HCTZ (n = 18,713), amlodipine (n = 11,520), lisinopril (n = 21,138), or valsartan
      (n = 9314). Over 1 year, 31% to 44% of subjects utilized no treatment for at
      least 60 days. Medication possession ratio (MPR) and adherence measures ranged
      from 73% to 90%. Valsartan was associated with significantly (P < .001) more
      favorable measures of persistence, length of therapy, time to discontinuation,
      MPR, and risk of discontinuation, compared with HCTZ, amlodipine, or lisinopril.
      The risk of discontinuation was 53%, 32%, and 14% greater for HCTZ, amlodipine,
      and lisinopril, respectively, versus valsartan (all comparisons P < .001).
      CONCLUSION: Among antihypertensive agents studied, valsartan was associated with
      the most favorable utilization patterns. Health care providers and systems should
      evaluate the use of antihypertensive drugs within their populations to identify
      and manage treatment discontinuation.

PMID- 17204739
TI  - National recommendations for preconception care: the essential role of the family
      physician.
AB  - The Centers for Disease Control and Prevention have published national
      recommendations for improving preconception health and health care in response to
      unfavorable aspects of the health status of women and children in the United
      States. The publication explains that the national recommendations are part of a
      strategic plan for improving preconception health through the provision of
      clinical care as well as the promotion of changes in individual behaviors, health
      policy, and public health strategies. The concept of preconception care has been
      articulated for well over a decade but has not become part of the routine
      practice of family medicine. Because all women of reproductive age presenting to
      the primary care setting are candidates for preconception care, the essential and
      critical role of family physicians in the provision of preconception care is
      apparent. As a specialty, we are now challenged to devise ways to effectively
      translate the concept of preconception care into clinical reality.

PMID- 17204740
TI  - Family medicine and the life course paradigm.
AB  - A unique characteristic of family physicians is that they seek to understand
      individual patients within the context of their families and larger social
      environments. Unfortunately, the intellectual development of family medicine is
      hampered by the reliance on epidemiologic, health service, and biomedical
      paradigms that are limited in their contextual perspectives on patients' lives.
      However, another paradigm, that of the life course, represents an
      interdisciplinary framework that views persons in context over time. It provides
      an ecological understanding of individual people by examining phenomena at the
      nexus of social pathways, developmental or health trajectories, and social
      change. A life course paradigm provides a way of thinking about patients in both
      proximal (eg, lived lives and family) and distal (eg, health care system)
      contexts over a life span. Five core principles define the life course as a
      paradigmatic framework: (1) human development and aging as lifelong processes,
      (2) human agency, (3) historical time and place, (4) the timing of events in a
      life, and (5) linked lives. At the individual level, the life course orients
      physicians to the opportunities and constraints that frame the health care
      choices, plans, and initiatives of people who maintain health and also face
      illness. At the organizational level, the life course offers an intellectual
      infrastructure for the New Model of Family Medicine by depicting an idealized
      delivery system that may be longitudinally integrated. It also emphasizes health
      and illness trajectories by linking health and other service organizations that
      assist individuals at different stages of their lives.

PMID- 17204741
TI  - Delay in diagnosis of diabetes mellitus due to inaccurate use of hemoglobin A1C
      levels.
AB  - Testing of hemoglobin A(1C) (HbA(1C)) levels has become widespread in the
      management of patients with diabetes mellitus. Since the 1980s, it has proven to
      be an invaluable tool correlating with a patient's average blood glucose levels
      as well as with their disease morbidity. Clinicians often base treatment
      decisions and make adjustments depending on a patient's HbA(1C) level. As useful
      as the HbA(1C) is, it does have notable limitations. A number of conditions can
      lead to a falsely elevated or a falsely low HbA(1C) level. When one of these
      conditions is present, it is important to recognize the inaccuracy of the HbA(1C)
      test to prevent a delay or error in the diagnosis or care of patients with
      diabetes mellitus. It is also important to be aware of alternative methods of
      monitoring a patient's diabetes such as a fructosamine assay or home and office
      blood glucose measurements. Presented is the case of a patient with diabetes
      mellitus and hereditary spherocytosis, a condition that interfered with her
      HbA(1C) value and resulted in a delay in her care.

PMID- 17204743
TI  - Mothers' comfort with screening questions.

PMID- 17204744
TI  - Will this exercise be good enough?

PMID- 17204745
TI  - Identification of amino acid determinants of dopamine 2 receptor synthetic
      agonist function.
AB  - The human dopamine 2 receptor (hD2R) modulates locomotor activity, hormone
      secretion, and neuropsychiatric function. Current knowledge of the hD2R structure
      is in large part derived from mutagenesis studies and molecular pharmacologic
      analysis together with homology modeling using bovine rhodopsin as a template. In
      this study, we utilized comparison of the Drosophila D2-like receptor (DD2R) with
      the hD2R as a novel approach for identifying candidate amino acids that are
      determinants of ligand potency and/or efficacy. We focused our studies on four
      dopaminergic ligands that are used in the treatment of Parkinson's disease:
      bromocriptine, pergolide, piribedil, and ropinirole. All four ligands are potent
      agonists at the wild-type hD2R, whereas only bromocriptine shows comparable
      function at the DD2R. We performed site-directed mutagenesis to replace hD2R
      amino acids (modeled to project into the ligand binding pocket) with
      corresponding fly residues, and vice versa. Substitution of three amino acids in
      the hD2R with the homologous DD2R residues (V91A, C118S, and L170I) led to a
      pronounced loss of pergolide potency and efficacy. A converse triple amino acid
      substitution of human residues into the fly receptor (DD2R-A133V/S160C/I211L)
      markedly enhanced pergolide efficacy and potency at the mutant DD2R. The same
      substitutions also converted piribedil and ropinirole, which lacked appreciable
      activity on the DD2R, to partial agonists. These findings show the important role
      of these three residues in drug-receptor interactions. Our study illustrates that
      comparison of a mammalian receptor with an invertebrate homolog complements
      previously described strategies for defining G protein-coupled receptor structure
      function relationships.

PMID- 17204746
TI  - Bifunctional alkylating agent-induced p53 and nonclassical nuclear factor kappaB
      responses and cell death are altered by caffeic acid phenethyl ester: a potential
      role for antioxidant/electrophilic response-element signaling.
AB  - Bifunctional alkylating agents (BFA) such as mechlorethamine (nitrogen mustard)
      and bis-(2-chloroethyl) sulfide (sulfur mustard; SM) covalently modify DNA and
      protein. The roles of nuclear factor kappaB (NF-kappaB) and p53, transcription
      factors involved in inflammatory and cell death signaling, were examined in
      normal human epidermal keratinocytes (NHEK) and immortalized HaCaT keratinocytes,
      a p53-mutated cell line, to delineate molecular mechanisms of action of BFA. NHEK
      and HaCaT cells exhibited classical NF-kappaB signaling as degradation of
      inhibitor protein of NF-kappaBalpha (IkappaBalpha) occurred within 5 min after
      exposure to tumor necrosis factor-alpha. However, exposure to BFA induced
      nonclassical NF-kappaB signaling as loss of IkappaBalpha was not observed until 2
      or 6 h in NHEK or HaCaT cells, respectively. Exposure of an NF-kappaB reporter
      gene-expressing HaCaT cell line to 12.5, 50, or 100 muM SM activated the reporter
      gene within 9 h. Pretreatment with caffeic acid phenethyl ester (CAPE), a known
      inhibitor of NF-kappaB signaling, significantly decreased BFA-induced reporter
      gene activity. A 1.5-h pretreatment or 30-min postexposure treatment with CAPE
      prevented BFA-induced loss of membrane integrity by 24 h in HaCaT cells but not
      in NHEK. CAPE disrupted BFA-induced phosphorylation of p53 and p90 ribosomal S6
      kinase (p90RSK) in both cell lines. CAPE also increased nuclear factor E2-related
      factor 2 and decreased aryl hydrocarbon receptor protein expression, both of
      which are involved in antioxidant/electrophilic response element (ARE/EpRE)
      signaling. Thus, disruption of p53/p90RSK-mediated NF-kappaB signaling and
      activation of ARE/EpRE pathways may be effective strategies to delineate
      mechanisms of action of BFA-induced inflammation and cell death signaling in
      immortalized versus normal skin systems.

PMID- 17204747
TI  - Inhibition of acrolein-induced apoptosis by the antioxidant N-acetylcysteine.
AB  - Acrolein is a highly electrophilic alpha,beta-unsaturated aldehyde to which
      humans are exposed in many situations. It is an environmental pollutant that is
      responsible for multiple respiratory diseases and has been implicated in
      neurodegenerative diseases such as Alzheimer's disease. The hypothesis of the
      study is that the antioxidant N-acetylcysteine (NAC), a precursor of glutathione,
      could protect cells against acrolein-induced apoptosis. Exposure of Chinese
      hamster ovary cells to a noncytotoxic dose of acrolein (4 fmol/cell) depleted
      intracellular glutathione to 45% of initial levels. NAC, which increased
      intracellular glutathione levels by 30%, afforded protection against acrolein
      induced cytotoxicity (loss of cell proliferation) and apoptosis. NAC protected
      against apoptosis by diminishing acrolein-induced activation of the mitochondrial
      death pathway. NAC inhibited acrolein-induced Bad translocation from the cytosol
      to the mitochondria, as well as Bcl-2 translocation from mitochondria to the
      cytosol, as evaluated by Western blot analysis. However, NAC had no effect on
      acrolein-induced Bax translocation to mitochondria and cytochrome c liberation
      into the cytosol. Meanwhile, NAC inhibited depolarization of mitochondrial
      membrane potential, as evaluated by rhodamine fluorescence using flow cytometry.
      NAC also inhibited procaspase-9 processing, activation of enzymatic activity of
      caspase-9, -7, and -8, and poly(ADP-ribose) polymerase cleavage induced by
      acrolein. Inhibition of acrolein-induced apoptosis using NAC was confirmed
      morphologically by diminished condensation of nuclear chromatin, as evaluated by
      fluorescence microscopy. These findings suggest that NAC could be potentially
      useful as a protective agent for people exposed to acrolein.

PMID- 17204748
TI  - Antilipolytic activity of a novel partial A1 adenosine receptor agonist devoid of
      cardiovascular effects: comparison with nicotinic acid.
AB  - Elevated lipolysis and circulating free fatty acid (FFA) levels have been linked
      to the pathogenesis of insulin resistance. A1 adenosine receptor agonists are
      potent inhibitors of lipolysis. Several A1 agonists have been tested as potential
      antilipolytic agents; however, their effect on the cardiovascular system remains
      a potential problem for development of these agents as drugs. In the present
      study, we report that CVT-3619 [(2-{6-[((1R,2R)-2-hydroxycyclopentyl) amino]
      purin9-yl} (4S,5 S,2R,3R)5-[(2fluorophenylthio) methyl] oxolane-3,4-diol)], a
      novel partial A1 receptor agonist, significantly reduces circulating FFA levels
      without any effect on heart rate and blood pressure in awake rats. Rats were
      implanted with indwelling arterial and venous cannulas to obtain serial blood
      samples, record arterial pressure, and administer drug. CVT-3619 decreased FFA
      levels in a dose-dependent manner at doses from 1 up to 10 mg/kg. The FFA
      lowering effect was blocked by the A1 receptor antagonist, 1,3-dipropyl-8
      cyclopentylxanthine. Triglyceride (TG) levels were also significantly reduced by
      CVT-3619 treatment in the absence and presence of Triton. Tachyphylaxis of the
      antilipolytic effect of CVT-3619 (1 mg/kg i.v. bolus) was not observed with three
      consecutive treatments. An acute reduction of FFA by CVT-3619 was not followed by
      a rebound increase of FFA as seen with nicotinic acid. The potency of insulin to
      decrease lipolysis was increased 4-fold (p < 0.01) in the presence of CVT-3619
      (0.5 mg/kg). In summary, CVT-3619 is an orally bioavailable A1 agonist that
      lowers circulating FFA and TG levels by inhibiting lipolysis. CVT-3619 has
      antilipolytic effects at doses that do not elicit cardiovascular effects.

PMID- 17204749
TI  - Pharmacological and pharmacokinetic properties of a structurally novel, potent,
      and selective metabotropic glutamate 2/3 receptor agonist: in vitro
      characterization of agonist (-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo[3.1.0]
      hexane-4,6-dicarboxylic acid (LY404039).
AB  - Group II metabotropic glutamate (mGlu) receptor agonists, including (1S,2S,5R,6S)
      2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate monohydrate (LY354740) and (-)-2
      oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268), have demonstrated
      efficacy in animal models of anxiety and schizophrenia, and LY354740 decreased
      anxiety in human subjects. Herein, we report the in vitro pharmacological profile
      and pharmacokinetic properties of another potent, selective, and structurally
      novel mGlu2/3 receptor agonist, (-)-(1R,4S,5S,6S)-4-amino-2
      sulfonylbicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY404039) and provide
      comparisons with LY354740. Similar to LY354740, LY404039 is a nanomolar potent
      agonist at recombinant human mGlu2 and mGlu3 receptors (K(i) = 149 and 92,
      respectively) and in rat neurons expressing native mGlu2/3 receptors (Ki = 88).
      LY404039 is highly selective for mGlu2/3 receptors, showing more than 100-fold
      selectivity for these receptors, versus ionotropic glutamate receptors, glutamate
      transporters, and other receptors targeted by known anxiolytic and antipsychotic
      medications. Functionally, LY404039 potently inhibited forskolin-stimulated cAMP
      formation in cells expressing human mGlu2 and mGlu3 receptors.
      Electrophysiological studies indicated that LY404039 suppressed electrically
      evoked excitatory activity in the striatum, and serotonin-induced l-glutamate
      release in the prefrontal cortex; effects reversed by LY341495. These
      characteristics suggest LY404039 modulates glutamatergic activity in limbic and
      forebrain areas relevant to psychiatric disorders; and that, similar to LY354740,
      it works through a mechanism that may be devoid of negative side effects
      associated with current antipsychotics and anxiolytics. Interestingly, despite
      the slightly lower potency (approximately 2-5-fold) of LY404039 versus LY354740
      in binding, functional, and electrophysiological assays, LY404039 demonstrated
      higher plasma exposure and better oral bioavailability in pharmacokinetic
      experiments. Collectively, the current data indicate that LY404039 may be
      valuable in the treatment of neuropsychiatric disorders, including anxiety and
      psychosis.

PMID- 17204750
TI  - Evidence based medicine: increasing, not dictating, choice.

PMID- 17204751
TI  - Germ theory: invisible killers revealed.

PMID- 17204752
TI  - Imaging: revealing the world within.

PMID- 17204753
TI  - Immunology: making magic bullets.

PMID- 17204754
TI  - Oral rehydration therapy: the simple solution for saving lives.

PMID- 17204755
TI  - The pill: emblem of liberation.

PMID- 17204756
TI  - Risks of smoking: all done and dusted.

PMID- 17204757
TI  - Sanitation: pragmatism works.

PMID- 17204758
TI  - Tissue culture: unlocking the mysteries of viruses and cancer.

PMID- 17204759
TI  - Vaccines: conquering untreatable diseases.

PMID- 17204760
TI  - Milestones on the long road to knowledge.

PMID- 17204761
TI  - I've got a little list.

PMID- 17204762
TI  - Let's pension off the "major breakthrough".

PMID- 17204763
TI  - Anaesthesia: symbol of humanitarianism.

PMID- 17204764
TI  - Antibiotics: the epitome of a wonder drug.

PMID- 17204765
TI  - Chlorpromazine: unlocking psychosis.

PMID- 17204766
TI  - Computers: transcending our limits?

PMID- 17204767
TI  - Discovery of structure of DNA: the best is yet to come.

PMID- 17204769
TI  - Communicating with parents on the neonatal unit.

PMID- 17204770
TI  - Lower urinary tract symptoms in men.

PMID- 17204772
TI  - GPs, operations, and the community.

PMID- 17204773
TI  - Ellipsis marks an important omission.

PMID- 17204774
TI  - Special report adds nothing new, say paper authors.

PMID- 17204775
TI  - Taste in food also changes.

PMID- 17204776
TI  - What of Asian, African, and South American patients?

PMID- 17204777
TI  - New contract reduces quality of patient-nurse relationship.

PMID- 17204778
TI  - GPs to follow up patients after surgery.

PMID- 17204779
TI  - Anaesthetist helps Italian patient who wanted to die.

PMID- 17204780
TI  - New MRSA strain is not at epidemic level, expert says.

PMID- 17204781
TI  - Hepatitis C morbidity is set to double in next decade.

PMID- 17204782
TI  - Dramatic drop in HIV infections halts circumcision trials.

PMID- 17204783
TI  - Outrage over death sentences in Libyan AIDS trial.

PMID- 17204784
TI  - High court upholds General Medical Council's rejection of case against
      neurologist.

PMID- 17204786
TI  - Doctors criticise proposal for community practitioners in rural India.

PMID- 17204787
TI  - FDA proposes changes in access and charges for experimental drugs.

PMID- 17204788
TI  - Planned changes in law on embryo research will hit researchers.

PMID- 17204789
TI  - Patients can opt out of controversial national records system.

PMID- 17204792
TI  - The Netherlands bans private stem cell therapy.

PMID- 17204793
TI  - Clicking for pills.

PMID- 17204794
TI  - Are medical secrets up for grabs?

PMID- 17204797
TI  - Sucked into the Herceptin maelstrom.

PMID- 17204798
TI  - In defence of a National Sickness Service.

PMID- 17204799
TI  - Should smokers be refused surgery?

PMID- 17204800
TI  - Should smokers be refused surgery?

PMID- 17204801
TI  - A new look at NHS commissioning.

PMID- 17204802
TI  - Acute gastroenteritis in children.

PMID- 17204803
TI  - Dyspepsia and Helicobacter pylori.

PMID- 17204805
TI  - Screening and assessing adolescent asthmatics for anxiety disorders.
AB  - The purpose of this study was to evaluate a strategy designed to permit early
      detection of anxiety disorders in adolescent asthmatics. Adolescents with asthma
      (N = 53) were screened for anxiety disorders using the Trait subscale of the
      State-Trait Anxiety Inventory for Children [STAI-C (Trait)] and the
      Multidimensional Anxiety Scale for Children (MASC). Adolescents and their parents
      were individually evaluated by a nurse trained in the administration of the
      Anxiety Disorders Interview Schedule-IV: Parent and Child Versions (ADIS-IV:
      P&C). Of the participants, 21 (40%) met the diagnostic criteria for one or more
      anxiety disorders. The STAI-C (Trait) was more effective than the MASC in
      screening adolescents for risk of coexisting anxiety disorders. Nurses trained to
      administer the ADIS-IV: P&C diagnosed anxiety disorders with a high degree of
      accuracy. These results have important implications for resolving the problem of
      unrecognized and untreated anxiety disorders in the adolescent asthmatic
      population.

PMID- 17204806
TI  - Relationships between caregiver stress and self-care behaviors in response to
      symptoms.
AB  - The specific aims of this study were to (a) identify relationships among care
      giving stress, caregivers' functional ability, and number of self-care behavior
      responses to physical and psychological symptoms in caregivers of persons with
      dementia and (b) examine the mediating function of functional ability in the
      relationship between caregiving stress and self-care behavior response to
      symptoms. A correlational, cross-sectional design was used, and a survey was
      mailed to 99 caregivers. The survey questionnaire contained items about
      demographics, caregiving stress, functional ability, and self-care behavior. The
      results indicate that caregivers who reported higher levels of caregiving stress
      had poorer self-rated health, poorer physical function, more symptoms, high
      levels of depressed mood, and more self-care behaviors. Caregiving stress was
      indirectly related to self-care behavior response to symptoms through functional
      ability, which suggests a need for developing early interventions to enhance the
      functional ability and self-care behaviors in response to some caregivers'
      symptoms.

PMID- 17204807
TI  - Actions taken by frail older widows to allow home care providers access to their
      homes.
AB  - Nurses have been advised to encourage older persons to keep their doors locked,
      but there is little guidance about how home care providers should best gain
      access to the homes of clients. During a descriptive phenomenological study of
      the experience of home care (N = 25), 9 frail older women explained their
      strategies for allowing providers access to their homes. Women who typically left
      their doors open for their own reasons were not uncomfortable leaving the door
      open when a provider was expected. However, women who left the door unlocked at
      the request of a provider expressed misgivings about doing so. Older women need
      personalized counseling about ensuring access to care providers while maximizing
      safety. For practical, ethical, and legal reasons, home care providers who ask
      older women to leave their doors open should reconsider that strategy.

PMID- 17204808
TI  - Medication use and symptoms in individuals with mitral valve prolapse syndrome.
AB  - Mitral valve prolapse (MVP) is a common valvular heart disease associated with a
      variety of frightening symptoms. Beta-adrenergic blockers along with calcium
      channel blockers and anxiolytics are widely used to treat symptoms associated
      with MVPS despite a lack of evidence that supports their efficacy. This study
      examined the relationship between prescribed medication use and frequency and
      intensity of MVPS symptoms. A descriptive cross-sectional survey design was used.
      Descriptive statistics and Cramer's V correlational analysis were used to answer
      the research questions. Self-completed questionnaires were mailed to 2,282 MVPS
      individuals older than 21 years of age throughout the United States and Canada
      previously diagnosed with MVPS. Of the 837 participants, 337 (40%) were taking
      one or more medications. Although there were significant positive correlations
      between anxiety and calcium channel blockers, chest pain and digoxin, and mood
      swings and digoxin, the correlations were very weak.

PMID- 17204809
TI  - Nursing home error and level of staff credentials.
AB  - Providing safe nursing home care is both a clinical and fiscal challenge in many
      countries. The fiscal realities result in the addition of other workers, such as
      medication technicians or aides (CMT/A), to the health care team. The purpose of
      this study was to determine the impact of various levels of credentialing among
      nursing home staff who deliver medications (RN, LPN, or CMT/A) on medication
      error. In addition, the impact of distractions and interruptions was explored.
      Using naive observation, 39 medication administrators representing various levels
      of credentialing were unobtrusively observed to determine the number of
      medication errors, distractions, and interruptions in five nursing homes. There
      were no differences in medication error rates by level of credential. However,
      RNs had more interruptions during their medication administration, and these
      increased interruptions were associated with increased medication error rates
      when wrong time errors were excluded (p = .0348).

PMID- 17204810
TI  - Nurses are vital providers of culturally competent care.

PMID- 17204811
TI  - Brief history of inclusion of content on culture in nursing education.
AB  - Nursing has a long history of focusing on the cultural dimension of care, dating
      back to Florence Nightingale and the early days of public health nursing. Nursing
      education studies advocated for including social science concepts in nursing
      curricula well before the founding of the first university school of nursing in
      the United States in 1910. A brief review of the highlights of major nursing
      curriculum, licensing, funding, accreditation studies, and initiatives reveals
      that culture competence in nursing education continues to receive increasing
      emphasis and support.

PMID- 17204812
TI  - Current approaches to integrating elements of cultural competence in nursing
      education.
AB  - Cultural competence in nursing education is receiving renewed emphasis.
      Curricular input to incorporate such knowledge, attitudes, and skills encompasses
      a wide variety of teaching and learning methods. Five are described here:
      specialty focus, required courses, models, immersion experiences, and distance
      learning or simulation. Despite progress in incorporating cultural content into
      nursing curricula, several issues characterize all levels of nursing programs,
      including lack of consensus on what should be taught, lack of standards, limited
      and inconsistent formal evaluation of effectiveness, a decline of curricular
      specialty courses on culture, a focus on the microlevel of the nurse-patient
      encounter, and the need for, support of, and preparation of faculty.

PMID- 17204813
TI  - The relationship between cultural competence education and increasing diversity
      in nursing schools and practice settings.
AB  - This article attempted to examine the relationship between cultural competence
      education and increasing diversity in nursing schools and practice settings. In
      addition to the review of the literature, a panel of experts was interviewed
      regarding institutional practices in response to the challenge of increasing
      diversity and cultural competence education. Evidence of positive outcomes of
      cultural competent care and impact of race and ethnic concordance between
      patients and providers are presented. The challenge of increasing
      underrepresented minorities in health care professions remains elusive. An
      ecological analysis is recommended to address the social and cultural barriers
      that transcend the micro system of the school and the macro system of the
      society. The challenge of increasing diversity and realizing outcomes of cultural
      competence education requires social and comprehensive remedies to level life
      inequities that perpetuate a history of disadvantages in some groups.

PMID- 17204814
TI  - Community-based approaches to strengthen cultural competency in nursing education
      and practice.
AB  - This article explores existing informal as well as formal approaches that address
      health disparities in the communities where they occur, enhancing the opportunity
      to strengthen the cultural competency of providers, students, and faculty. A
      particular focus centers on the community-based participatory research approaches
      that involve community members, providing opportunities to develop mutually
      respectful, trusting relationships through co-teaching and co-learning
      experiences. With community-based participatory research approaches to community
      involvement in place, the stage is set for partnerships between communities and
      schools of nursing to collaboratively design, implement, and integrate informal
      and formal cultural competence components in nursing curricula.

PMID- 17204815
TI  - Extending cultural competence through systems change: academic, hospital, and
      community partnerships.
AB  - Work on cultural competence has a long history in nursing, yet we have not
      successfully institutionalized these attitudes and skills throughout education
      and practice. An effective approach to promoting widespread cultural competence
      is to work at the system level in which coalitions of community agencies partner
      with academic and health care organizations. A systems approach includes all
      health practitioners, reducing current discrepancies across disciplines, and
      establishes cultural competence as the standard. Work in and with communities
      places students and practitioners more consistently in cross-cultural
      circumstances. Implementing this vision will require national as well as local
      leadership across public and private sectors.

PMID- 17204816
TI  - Computational models of neocortical neuronogenesis and programmed cell death in
      the developing mouse, monkey, and human.
AB  - This paper presents a computational model allowing quantitative simulations of
      acquisition of neocortical neuronal number across mammalian species. When
      extrapolating scientific findings from rodents to humans, it is particularly
      pertinent to acknowledge the importance of the accelerated enlargement of the
      neocortex during human evolution. Neocortex development is marked by discrete
      stages of neural progenitor cell proliferation and death, neuronal
      differentiation, and neuronal programmed cell death. We have developed
      computational models of human and rhesus monkey neocortical neuronal cell
      acquisition based on experimentally derived parameters of cell cycle length,
      commitment to cell cycle exit, and cell death. Our model results agree with
      independent stereological studies estimating neocortical neuron number in adult
      and developing rhesus monkey and human. Comparisons of our primate models with
      previously developed rodent models suggest correlations between the lengthening
      of the duration of the neuronogenesis period and a lengthening of the cellular
      processes of cell cycle progression and death can account for the vast increase
      in size of the primate neocortex. Furthermore, when compared with rodents, we
      predict that cell death may play a larger role in shaping the primate neocortex.
      Our mathematical models of the development and evolution of the neocortex provide
      a quantitative, biologically based construct for extrapolation between rodent and
      humans. These models can assist in focusing future experimental research on the
      differing mechanisms of rodent versus human neocortical development.

PMID- 17204817
TI  - Working memory specific activity in auditory cortex: potential correlates of
      sequential processing and maintenance.
AB  - Working memory (WM) tasks involve several interrelated processes during which
      past information must be transiently maintained, recalled, and compared with test
      items according to previously instructed rules. It is not clear whether the rule
      specific comparisons of perceptual with memorized items are only performed in
      previously identified frontal and parietal WM areas or whether these areas
      orchestrate such comparisons by feedback to sensory cortex. We tested the latter
      hypothesis by focusing on auditory cortex (AC) areas with low-noise functional
      magnetic resonance imaging in a 2-back WM task involving frequency-modulated (FM)
      tones. The control condition was a 0-back task on the same stimuli. Analysis of
      the group data identified an area on right planum temporale equally activated by
      both tasks and an area on the left planum temporale specifically involved in the
      2-back task. A region of interest analysis in each individual revealed that
      activation on the left planum temporale in the 2-back task positively correlated
      with the task performance of the subjects. This strongly suggests a prominent
      role of the AC in 2-back WM tasks. In conjunction with previous findings on FM
      processing, the left lateralized effect presumably reflects the complex
      sequential processing demand of the 2-back matching to sample task.

PMID- 17204818
TI  - Task-related modulation of early cortical responses during language production:
      an event-related synthetic aperture magnetometry study.
AB  - We used whole-head magnetoencephalography measurements to investigate the
      spatiotemporal pattern of neural activity related to language production. Eight
      participants overtly responded by repeating aloud or vocalizing an internally
      generated verb to auditorily or visually presented nouns. Activity peaked within
      primary sensory (auditory or visual) cortices between 75 and 130 ms after
      stimulus onset, association cortices (inferior and superior temporal gyri)
      between 130 and 170 ms, and inferior frontal and premotor areas between 150 and
      240 ms. Common to auditory and visual modalities, peak activity at about 220 ms
      was significantly larger in bilateral inferior frontal and left precentral
      regions when participants generated a verb than when they repeated a noun. These
      early differences in frontal regions may reflect the allocation of resources to
      the processing of low-level perceptions that are projected to the premotor areas
      early in the preparation of language production.

PMID- 17204819
TI  - Plastic phase-locking and magnetic mismatch response to auditory deviants in
      temporal lobe epilepsy.
AB  - The magnetic equivalent (MMNm) of mismatch negativity may reflect auditory
      discrimination and sensory memory. To study whether temporal lobe epilepsy (TLE)
      affects automatic central auditory-change processing, we recorded
      magnetoencephalographic (MEG) responses to standard and duration-deviant sounds
      in 12 TLE patients and 12 age-matched controls, and repeated MEG measurement in 8
      patients 6-30 months following epilepsy surgery and in 6 controls 3-8 months
      after their first measurement. We compared the MMNm between patients and
      controls, and also evaluated intertrial phase coherences as indexed by phase
      locking factors (PLF) using wavelet-based analyses. We observed longer MMNm
      latencies for patients than for controls. Dipole modeling and minimum-current
      estimates together showed bi-frontotemporal sources for MMNm. The phase locking
      across trials was dominant at the 4- to 14-Hz band, and the main difference in
      PLF between deviant- and standard-evoked responses occurred in the time frame of
      150-250 ms after stimulus onset. Notably, in the 5 patients who became seizure
      free after removal of right temporal epileptic focus, the phase-locking phenomena
      resulting from deviant stimuli were enhanced, and even more distributed in the
      frontotemporal regions. We conclude that mesial TLE might affect auditory-change
      detection, and a successful surgery causes a possible plastic change in phase
      locking of deviant-evoked signals.

PMID- 17204820
TI  - Age effects on the neural correlates of episodic retrieval: increased cortical
      recruitment with matched performance.
AB  - Functional neuroimaging investigations have revealed a range of age-related
      differences in the neural correlates of episodic memory retrieval. Typically,
      whereas activity is reduced in older compared with younger adults in some
      regions, other regions are engaged exclusively, or to a greater extent, in older
      adults. It is unclear whether such differences merely represent the neural
      correlates of the lower levels of memory performance and impaired recollection
      typical of older adults. This issue was addressed in the present event-related
      functional magnetic resonance imaging study. The level of recollection was
      matched between groups of healthy younger and older adults for a subset of
      picture items in a source memory task by manipulating the number of study
      presentations. Contrasts of the activity elicited by old items attracting correct
      source judgments and correctly identified new items revealed that the 2 groups
      recruited many of the same brain regions. However, a striking pattern of age
      related differences was also observed. In older adults, retrieval-related
      increases in activity were more widespread and of greater magnitude than in the
      young. Moreover, regions demonstrating retrieval-related decreases in activity
      were almost absent in the older participants. These findings suggest an age
      related decline in the efficiency with which neural populations support cognitive
      function.

PMID- 17204821
TI  - Spatio-temporal analysis of feature-based attention.
AB  - The cortical mechanisms of feature-selective attention to color and motion cues
      were studied in humans using combined electrophysiological,
      magnetoencephalographic, and hemodynamic (functional magnetic resonance imaging)
      measures of brain activity. Subjects viewed a display of random dots that
      periodically either changed color or moved coherently. When attention was
      directed to the color change it elicited enhanced neural activity in visual area
      V4v, previously shown to be specialized for processing color information. In
      contrast, when dot movement was attended it produced enhanced activity in the
      motion-specialized area human MT. Parallel recordings of event-related
      electrophysiological and magnetoencephalographic responses indicated that the
      attention-related facilitation of neural activity in these specialized cortical
      areas occurred rapidly, beginning as early as 90-120 ms after stimulus onset. We
      conclude that selection of an entire feature dimension (motion or color) boosts
      neural activity in its specialized cortical module much more rapidly than does
      selection of one feature value from another (e.g., one color from another), as
      reported in previous electrophysiological studies. By combining methods with high
      spatial and temporal resolution it is possible to analyze the precise time course
      of feature-selective processing in specialized cortical areas.

PMID- 17204822
TI  - Recollection and the reinstatement of encoding-related cortical activity.
AB  - The neural correlates of episodic memory retrieval ("recollection") differ
      according to the type of information contained in the recollected episode. Such
      content-specific recollection effects have been hypothesized to reflect the
      reinstatement of processes or representations active during encoding. Using event
      related functional magnetic resonance imaging, we evaluated this hypothesis by
      directly contrasting the neural activity elicited during the encoding and
      subsequent recollection of words studied with one of 2 encoding tasks. Study
      words appearing on pictures of scenes required imagining the word's referent at
      any location within the scene, whereas words appearing on a blank background
      required generating a sentence that incorporated the word. On a later memory
      test, the neural correlates of recollection were operationalized by contrasting
      the activity elicited during correct "remember" versus "know" responses.
      Recollected words from the "scene" task elicited activity in regions of left
      occipital cortex and anterior fusiform gyrus that overlapped regions where
      encoding-related activity was greater for the scene than sentence task.
      Conversely, activity elicited by words recollected from the "sentence" task
      overlapped with a region of ventromedial frontal cortex where encoding-related
      activity was greater for the sentence task. These content-specific associations
      between encoding- and recollection-related neural activity strongly support the
      reinstatement hypothesis of episodic retrieval.

PMID- 17204824
TI  - Small-world anatomical networks in the human brain revealed by cortical thickness
      from MRI.
AB  - An important issue in neuroscience is the characterization for the underlying
      architectures of complex brain networks. However, little is known about the
      network of anatomical connections in the human brain. Here, we investigated large
      scale anatomical connection patterns of the human cerebral cortex using cortical
      thickness measurements from magnetic resonance images. Two areas were considered
      anatomically connected if they showed statistically significant correlations in
      cortical thickness and we constructed the network of such connections using 124
      brains from the International Consortium for Brain Mapping database. Significant
      short- and long-range connections were found in both intra- and interhemispheric
      regions, many of which were consistent with known neuroanatomical pathways
      measured by human diffusion imaging. More importantly, we showed that the human
      brain anatomical network had robust small-world properties with cohesive
      neighborhoods and short mean distances between regions that were insensitive to
      the selection of correlation thresholds. Additionally, we also found that this
      network and the probability of finding a connection between 2 regions for a given
      anatomical distance had both exponentially truncated power-law distributions. Our
      results demonstrated the basic organizational principles for the anatomical
      network in the human brain compatible with previous functional networks studies,
      which provides important implications of how functional brain states originate
      from their structural underpinnings. To our knowledge, this study provides the
      first report of small-world properties and degree distribution of anatomical
      networks in the human brain using cortical thickness measurements.

PMID- 17204823
TI  - Hippocampal activation for autobiographical memories over the entire lifetime in
      healthy aged subjects: an fMRI study.
AB  - We used functional magnetic resonance imaging to determine the cerebral
      structures required during the recollection of episodic autobiographical memories
      according to 5 time periods covering the whole lifespan to test the 2 concurring
      models of memory consolidation, which propose either a temporary (standard model)
      or a permanent (multiple-trace model) role of the hippocampus in episodic memory
      retrieval. The experimental paradigm was specially designed to engage subjects
      (67.17 +/- 5.22 years old) in the retrieval of episodic autobiographical
      memories, whatever the time period, from personally relevant cues selected by
      questioning a family member. Moreover, the nature of the memories was checked at
      debriefing by means of behavioral measures to control the degree of episodicity.
      Behavioral data showed that recollected memories were characterized by
      specificity and details whatever their remoteness. Main neuroimaging data
      (Statistical Parametric Mapping 99) revealed the activation of a network
      including the left superior frontal gyri, bilateral precuneus/posterior cingulate
      and lingual gyri, left angular gyrus, and left hippocampus, although the
      subtraction analyses detected subtle differences between certain time periods.
      Small volume correction centered on the hippocampus detected left hippocampal
      activation for all time periods and additional right hippocampal activation for
      the intermediate periods. Further confirmation was provided by using a 3-way
      analysis of variance on blood oxygen level-dependent values, which revealed
      hippocampal activation whatever the time interval. The present data challenge the
      standard model of memory consolidation and support the multiple-trace model,
      instead. The comparison with previous literature stresses the idea that a
      bilateral involvement of the hippocampus characterizes rich episodic
      autobiographical memory recollection.

PMID- 17204825
TI  - Urinary incontinence, catheters, and urinary tract infections: an overview of CMS
      tag F 315.
AB  - The majority of nursing home residents experience some type of urinary
      incontinence. Other bladder-related disorders (eg, urinary retention and urinary
      tract infection) also are common in long-term care facilities. Efforts to manage
      urological conditions such as the use of indwelling catheters and absorbent
      products, perineal hygiene and care, toileting, and bladder rehabilitation are
      areas of concern and have become the subject of revised regulations. The intent
      of recent changes to the Centers for Medicare and Medicaid Services surveyor
      guidance for incontinence and urinary catheters is to ensure that: 1) incontinent
      residents are identified, assessed, and provided appropriate treatment, 2)
      indwelling catheters are not used without medical justification and removed as
      soon as clinically warranted, and 3) residents receive appropriate care to
      prevent urinary tract infections. Nursing homes must implement policies,
      procedures, and programs to help restore bladder function and continence in order
      to improve quality-of-life for nursing home residents.

PMID- 17204826
TI  - Incontinence-associated skin damage in nursing home residents: a secondary
      analysis of a prospective, multicenter study.
AB  - More than half of the nursing home population is incontinent of urine or feces,
      presenting challenges to perineal skin health. To determine the occurrence and
      severity of skin damage in nursing home residents with incontinence, a secondary
      analysis of data collected from a multisite, open-label, quasi-experimental study
      of cost and efficacy of four regimens for preventing incontinence-associated
      dermatitis in nursing home residents was performed. Sixteen randomly selected
      nursing homes from across the US were included in the study. Participating
      nursing home residents were incontinent of urine and/or feces and free of skin
      damage. Of the 1,918 persons screened, 51% (n = 981) qualified for prospective
      surveillance. Perineal skin was assessed over a 6-week period; frequency, type,
      and severity of skin damage were observed. Skin damage developed after a median
      of 13 (range 6 to 42) days in 45 out of 981 residents (4.6%), of which 3.4% was
      determined to be incontinence-associated dermatitis. Some residents (14 out of
      45, 31%) had incontinence-associated dermatitis of other skin damage in more than
      one area. This study is one of the first to report the characteristics of
      incontinence-associated dermatitis in a large sample of nursing home residents.
      The sample size and random selection of nursing homes impart generalizability to
      the findings. Incontinence-associated dermatitis is a risk in nursing home
      residents, especially those with fecal incontinence. These findings suggest that
      the rate and severity of incontinence-associated dermatitis are low with close
      monitoring and use of a defined skin care regimen that includes a pH-balanced
      cleanser and moisture barrier.

PMID- 17204827
TI  - Fecal incontinence in acutely and critically ill patients: options in management.
AB  - Fecal incontinence presents a major challenge in the comprehensive nursing care
      of acutely and critically ill patients. When manifested as diarrhea, the effects
      of fecal incontinence can range from mild (superficial skin irritation) to
      profound (severe perineal dermatitis, dehydration, electrolyte imbalance, and
      sepsis). Fecal incontinence has many etiologies and risk factors. These include
      damage to the anal sphincter or pelvic floor, liquid stool consistency, abnormal
      colonic transport, and decreased intestinal capacity. To avoid or minimize
      complications, the cause of diarrhea should be addressed, fecal leakage
      prevented, stool contained, and skin integrity preserved. Management options
      addressing these goals include diet, pharmacological therapy, and the use of
      containment products. Management options and their respective advantages and
      disadvantages are presented with a special focus on safety issues. Diverse
      approaches are safe only if they are knowledgeably selected, carefully
      instituted, and constantly monitored for their effects on patient outcomes.
      Research to identify which options work best in selected clinical situations and
      which combinations of therapies are most effective is needed.

PMID- 17204828
TI  - Correlating the Fecal Incontinence Quality-of-Life Score and the SF-36 to a
      proposed Ostomy Function Index in patients with a stoma.
AB  - Quality of life is affected by the creation of a stoma. To assess the validity of
      the Ostomy Function Index in patients with a stoma, a prospective survey was
      conducted from July 2000 to September 2001 among patients participating in local
      United Ostomy Association chapters (N = 99; 55 with a colostomy and 44 with an
      ileostomy). The Short Form 36 general health survey, Fecal Incontinence Quality
      of Life Scale, and the proposed Cleveland Clinic Florida Ostomy Function Index
      were used to assess general health and stoma function in patients with an ostomy.
      The average proposed function index score (7 = excellent function, 35 = poor
      function) was 11.97 (range 7 to 22). The proposed function Index correlated with
      the Fecal Incontinence Quality of Life Scale and the physical and mental
      component scales of the SF-36 (P < 0.05). The correlation between the proposed
      function index and the Fecal Incontinence Quality of Life Scale was stronger in
      colostomy than in ileostomy patients. With the exception of the SF-36 role
      emotional domain in ileostomy patients, the function index correlated with all SF
      36 scales (P <0.05) in both patient groups. The results of this study suggest
      that ostomy function is variable and correlates with quality of life and that the
      Fecal Incontinence Quality of Life Scale offers a limited assessment of quality
      of life in colostomy patients. The Cleveland Clinic Florida Ostomy Function Index
      offers an objective assessment of ostomy function that reflects on quality of
      life. Additional studies to refine measurement of quality of life in stoma
      patients are warranted.

PMID- 17204829
TI  - Selective serotonin reuptake inhibitors reduce the attack frequency in familial
      mediterranean Fever.
AB  - Familial Mediterranean Fever (FMF) is characterized by recurrent acute attacks of
      fever and serositis, and colchicine is the primary treatment. The pathogenesis of
      the disease has not been fully understood. Resistance to colchicine remains to be
      a problem in up to 30% of the patients and yet there seems to be no alternative
      treatment. In this study our objective was to investigate whether a selective
      serotonin re-uptake inhibitor (SSRI) could affect the attack frequency and acute
      phase response in FMF patients who were unresponsive to colchicine. We
      retrospectively evaluated the hospital files of 11 colchicine-unresponsive FMF
      patients who had been treated with SSRIs. According to the records and re
      evaluation of the patients, the total number of the FMF attacks was calculated
      before and after the SSRI, adjunct to colchicine. The laboratory values including
      erythrocyte sedimentation rate, C-reactive protein, fibrinogen and white blood
      cell counts were also noted before and after the SSRI treatment from their
      hospital files. The mean attack frequency before adding SSRI to colchicine was
      8.09 +/- 3.53 per 6 months, and at the end of this period there was a great
      decline in the number of mean attack frequency (0.36 +/- 0.50 attacks per 6
      months) (p < 0.001). Acute phase reactants were significantly decreased after
      SSRI treatment (p < 0.001). All of the colchicine-unresponsive patients had
      depression and 3 of those patients also had fibromyalgia. SSRIs appear to be
      useful adjuncts in the management of FMF patients who continue to have attacks
      despite regular colchicine treatment.

PMID- 17204830
TI  - Antibiotic-resistant Pseudomonas aeruginosa in cystic fibrosis.

PMID- 17204831
TI  - Evidence for decreased circulating apelin beyond heart involvement in uremic
      cardiomyopathy.
AB  - BACKGROUND: Plasma apelin concentration in heart failure has been described in
      small studies reporting conflicting results. In hemodialysis (HD) patients,
      apelin decreased more in those with more severe heart involvement. It is unclear
      if uremia is connected to this reduction irrespective of heart failure. We
      compared apelin in two cardiomyopathies with different renal function. METHODS:
      Observational study conducted in 30 adult Caucasian outpatients in class I NYHA
      not affected by diabetes or ischemic heart, 15 with idiopathic dilated
      cardiomyopathy (DCM) and 15 with uremic dilated cardiomyopathy undergoing HD.
      Plasma apelin, creatinine, high-sensitivity C-reactive protein, endothelin, NT
      proB-type natriuretic peptide (NT-proBNP), and Doppler echocardiogram were
      evaluated. RESULTS: Heart involvement was more severe in the DCM patients (lower
      ejection fraction, greater diastolic volume index, and worse index of myocardial
      performance). Median value of apelin in HD patients (19.1 pg/ml) was one third of
      that in DCM patients (58.2 pg/ml) whereas creatinine, NT-proBNP, and C-reactive
      protein were 11, 80, and 9 times higher respectively in HD than in DCM patients.
      Median values of endothelin were comparable in both groups. Apelin was not
      significantly correlated with any variable. CONCLUSION: Uremic status was the
      determinant for decreased plasma apelin in HD patients regardless of the severity
      of heart involvement.

PMID- 17204832
TI  - Risk factors for sudden cardiac death in patients with chronic renal
      insufficiency and left ventricular dysfunction.
AB  - BACKGROUND: Patients with ischemic left ventricular dysfunction have a high risk
      of sudden cardiac death (SCD). It is, however, unclear if the risk and risk
      factors of SCD in these patients is modulated by the coexistence of mild chronic
      renal insufficiency. METHODS: We performed a post-hoc analysis of the outcome
      associated with mild renal dysfunction, as defined by an estimated glomerular
      filtration rate (eGFR) of <75 ml/min/1.73 m2 in patients allocated to the
      conventional medical therapy arm of the Multicenter Automatic Defibrillator
      Implantation Trial-II. RESULTS: In multivariable analysis, renal dysfunction was
      independently associated with significant increased risks for all-cause mortality
      (hazard ratio [HR] = 1.86; 95% CI 1.13-3.05) and SCD (HR = 2.00; 95% CI 1.01
      4.02), but not non-SCD, compared to patients without renal dysfunction.
      Independent predictors of SCD in patients with renal dysfunction were: increased
      resting heart rate (HR = 2.40; 95% CI 1.50-3.86); low diastolic blood pressure
      (HR = 3.23; 95% CI 1.52-6.66), and a prolonged QRS duration (HR = 1.63; 95% CI
      1.02-2.61). Beta-blocker therapy was independently associated with a significant
      reduction in the risk of SCD in patients with an eGFR of <75 ml/min/1.73 m2 (HR =
      0.61; 95% CI 0.38-0.99). CONCLUSION: These findings suggest that renal
      dysfunction significantly increases the risk for SCD in patients with left
      ventricular dysfunction, and that beta-blocker therapy reduces the risk of
      arrhythmic mortality in heart failure patients with coexisting renal
      insufficiency.

PMID- 17204833
TI  - Albumin activation of NAD(P)H oxidase activity is mediated via Rac1 in proximal
      tubule cells.
AB  - BACKGROUND: Rac1 is a Rho-family small GTP-ase, when activated is pivotal in
      NAD(P)H oxidase (NOX) activation and generation of reactive oxygen species (ROS).
      Evidence links Rac1 activation to receptor-mediated albumin endocytosis in the
      proximal tubule cell (PTC). Thus in states of albumin overload, Rac1 activation
      could lead to NOX activation and ROS formation in the PTC. Furthermore,
      accumulating evidence supports that HMG-CoA reductase inhibition may reduce
      oxidative stress and albuminuria. METHODS: To investigate the role of HMG-CoA
      reductase inhibition of Rac1 and oxidative stress we used the opossum kidney PTC.
      ROS generation in the PTC was confirmed using oxidative fluorescent
      dihydroethidium staining. RESULTS: We observed time-dependent increases in NOX
      activity with bovine serum albumin (albumin) stimulation (500 microg/dl, maximum
      at 20 min, p < 0.05) that was inhibited in a concentration-dependent manner with
      the HMG-CoA reductase inhibitor rosuvastatin (1 microM, p < 0.05). Additionally,
      the Rac1 inhibitor NSC23766 (100 ng/ml) attenuated albumin activation of NOX.
      Western blot analysis confirmed Rac1 translocation to plasma membrane in the PTC
      following albumin stimulation and subsequent inhibition by rosuvastatin and
      NSC23766. CONCLUSIONS: These data demonstrate that albumin-mediated increases in
      NOX activity and ROS in PTC are reversed by inhibition of Rac1 signaling with the
      use of rosuvastatin.

PMID- 17204834
TI  - Increased risk of cerebral hemorrhage in Chinese male heavy drinkers with mild
      liver disorder.
AB  - BACKGROUND: Epidemiological evidence suggests that heavy alcohol consumption
      increases the risk for either stroke or liver disease. The goal of this study was
      to determine whether heavy drinkers with mild liver disorder (MLD) are at risk of
      hemorrhagic stroke. METHODS: All of the 524 patients recruited were males with a
      first-ever acute stroke and were consecutively admitted to the Tri-Service
      General Hospital between January 2000 and December 2001. The risk factors, liver
      function, stroke subtypes, and hemostatic factors were assessed among 68 patients
      defined as heavy drinker stroke (HDS) and 456 patients as non-heavy drinker
      stroke (NHDS). RESULTS: HDS patients had a significantly higher incidence of
      hemorrhagic stroke than NHDS patients. HDS patients were also associated with
      significantly higher occurrence of cigarette smoking, hyperuricemia, liver
      dysfunction, and significantly lower platelet counts. HDS patients with MLD were
      more likely to have hemorrhagic stroke (76.5%) than HDS patients without MLD
      (33.3%) and NHDS patients with (40.3%) or without (26.7%) MLD. HDS patients with
      MLD also exhibited a significantly higher glutamic oxaloacetic
      transaminase/glutamic pyruvic transaminase ratio (2.0 +/- 1.2) and lower platelet
      number (185,000 +/- 85,000 per microl) when compared with HDS patients without
      MLD (1.4 +/- 0.5; 206,000 +/- 59,000 per microl) and NHDS patients with (1.1 +/-
      1.0; 256,000 +/- 97,000 per microl) or without (1.4 +/- 0.7; 216,000 +/- 68,000
      per microl) MLD. CONCLUSIONS: HDS patients with MLD are at higher risk for
      hemorrhagic stroke in part due to the changes in hemostatic factors, although
      other factors may also contribute to hemorrhagic stroke.

PMID- 17204835
TI  - Development of gene vectors for pinpoint targeting to human hepatocytes by
      cationically modified polymer complexes.
AB  - We developed a vector that might enable gene therapy of metabolic liver disease
      or hepatoma. Here we demonstrate the use of cationically modified biocompatible
      phospholipid polymer conjugated with hepatitis B surface (HBs) antigen for the
      specific transfer of genes into human hepatocytes. Poly(2-methacryloyloxyethyl
      phosphorylcholine (MPC)- co-N,N-dimethylaminoethyl methacrylate (DMAEMA)-co- p
      nitrophenylcarbonyloxyethyl methacrylate(NPMA))(polyMDN) was prepared as a frame
      of vector. The specific expression of sFlt-1 or GFP by polyMDN conjugated with
      HBs containing plasmid (plasmid/polyMDN-HBs), polyMDN containing plasmid
      (plasmid/polyMDN), plasmid only and PBS were assessed in tumor cells (HepG2 or
      WiDr) in vitro and in vivo. The histological findings, organ weight changes, and
      degree of liver dysfunction were examined in the mice administered by several
      reagents. The sFlt-1 and GFP expression was observed only in the HepG2 cells
      transfected with sFlt-1 or GFP/polyMDN-HBs. None of the side effects mentioned
      above was observed. In conclusion, these results suggest that polyMDN-HBs is a
      human hepatocyte-specific gene delivery vector that might not have serious side
      effects.

PMID- 17204836
TI  - Microvascular decompression in trigeminal neuralgia with no vascular compression.
AB  - BACKGROUND: Microvascular decompression (MVD) is a well-known surgical procedure
      with one of the best long-term results in the therapy of trigeminal neuralgia.
      But the exact pathophysiology of this disease has not yet been elucidated. Cases
      with undetectable vascular compression who are cured after MVD make this dilemma
      clear. Autopsy studies have also shown vascular compression in asymptomatic
      cases. METHODS: Five of 40 cases with TN treated with MVD in our clinic had no
      visible vascular compression. Diagnosis was made with MRI and MRA. RESULTS:
      Surprisingly all of these 5 patients were cured with MVD. Two of them needed only
      one operation to become pain free and 3 a second operation. CONCLUSION: We think
      that the therapeutic effect of MVD is due to minimal trauma of the nerve. It
      seems that MVD is a good alternative strategy with low complication rates in
      comparison to ablative procedures.

PMID- 17204837
TI  - Effects of growth hormone on growth, insulin resistance and related hormones
      (ghrelin, leptin and adiponectin) in Turner syndrome.
AB  - BACKGROUND: Concomitant evaluation of the metabolic and growth-promoting effects
      of growth hormone (GH) therapy in Turner syndrome (TS) may be used in the
      prediction of the growth response to GH therapy. AIM: To evaluate the metabolic
      effects of GH therapy in TS and correlation with the short-term growth response.
      PATIENTS: 24 prepubertal children with TS, aged 9.4 +/- 2.6 years were followed
      for auxology and IGF-I, IGFBP-3, leptin, ghrelin, adiponectin, lipids and OGTT
      results in a prospective multicenter study. INTERVENTION: GH (Genotropin) in a
      dose of 50 microg/kg/day for 1 year. RESULTS: Height standard deviation score
      (SDS) increased from -3.9 +/- 1.5 to -3.5 +/- 1.4 (p = 0.000) on therapy. BMI did
      not change. IGF-I SDS increased from -2.3 +/- 0.4 to -1.6 +/- 1.1 at 3 and 6
      months (p = 0.001) and decreased thereafter. Serum leptin decreased significantly
      from 2.3 +/- 3.9 to 1.7 +/- 5.3 ng/ml (p = 0.022) at 3 months and increased
      afterwards. Serum ghrelin decreased from 1.2 +/- 0.8 to 0.9 +/- 0.4 ng/ml (p =
      0.005) with no change in adiponectin. Basal and stimulated insulin levels also
      increased significantly. Delta height SDS over 1 year showed a significant
      correlation with Delta IGF-I(0-3 months) (r = 0.450, p = 0.027). CONCLUSION: IGF
      I may be considered as a marker of growth response in TS at short term. Leptin
      shows a decrease at short term but does not have a correlation with growth
      response. The decrease in ghrelin in face of unchanged weight seems to be
      associated with increase in IGF-I and insulin levels. The unchanged adiponectin
      levels in spite of an increase in insulin levels indicates that adiponectin is
      mainly affected by weight, not insulin.

PMID- 17204838
TI  - Insulin but not phlorizin treatment induces a transient increase in GLUT2 gene
      expression in the kidney of diabetic rats.
AB  - BACKGROUND/AIMS: Increases in the renal glucose transporter gene expression are
      involved in renal tubule-glomerular diseases. Here we investigate the GLUT2 gene
      expression changes in the kidney of diabetic rats, by using insulin or phlorizin
      treatment. METHODS: Rats were rendered diabetic and studied 20 days later: 4-12 h
      after one single injection of insulin or phlorizin, and 1-6 days after insulin or
      phlorizin injection twice a day, comparing with diabetic rats injected with
      placebo. GLUT2 was investigated by Northern and Western analysis. RESULTS: In 20
      day diabetic rats, acute treatment with insulin lowered the plasma glucose and
      increased the GLUT2 mRNA ( approximately 100%, p < 0.001) without changes in the
      protein content, while phlorizin lowered the plasma glucose, but changed neither
      the GLUT2 mRNA nor the protein expression. Twenty-four hours of insulin treatment
      increased both GLUT2 mRNA ( approximately 100%, p < 0.001) and protein (
      approximately 50%, p < 0.01), but no effects of phlorizin were observed. After 6
      days, insulin and phlorizin similarly reduced glycemia, with opposite effects
      upon plasma insulin and urinary glucose, and both treatments decreased GLUT2 mRNA
      and protein (p < 0.05). CONCLUSION: In kidney of diabetic rats, an initial and
      transient upregulation of GLUT2 was induced specifically by insulin only. The 6
      day normalization of GLUT2, however, was induced by both insulin and phlorizin
      treatment, which seems to be related to the plasma glucose lowering.

PMID- 17204839
TI  - Autophagy and cell-death proteases in plants: two wheels of a funeral cart.
AB  - Apoptosis is an evolutionarily young cell-death strategy evolved to disassemble
      animal cells through the action of the caspase family of proteases and phagocytic
      clearance. This strategy does not work in plants, which instead feature a
      phylogenetically older autophagic programmed cell death (PCD), as a bona fide
      type of cellular suicide. Recent work has begun to address the mechanistic roles
      for autophagic and proteolytic components, as well as their possible cooperation
      in plant PCD. A recent study has shown autophagosomal localization of a key cell
      death proteolytic activity at the early stage of plant PCD. Here we focus on the
      relationship between autophagic and proteoloytic components in plant PCD at the
      cellular and organismal levels.

PMID- 17204840
TI  - 4th International Symposium on Autophagy: exploiting the frontiers of autophagy
      research.
AB  - The 4th International Symposium on Autophagy was held in Mishima, a small town
      between Tokyo and Kyoto, October 1-5, 2006 (http://isa4th.umin.jp/). The meeting
      was organized by the group of Eiki Kominami. Approximately 150 participants took
      part in this well-organized meeting in the spacious and comfortable Toray
      Conference Hall (Fig. 1). The social program offered opportunities for informal
      discussions, Japanese culture (from karaoke singing to traditional drumming; Fig.
      2), history and nature (a visit to a steaming volcano; Fig. 3), as well as
      delicious Japanese food. The scientific program started with two plenary lectures
      on Sunday evening. Daniel Klionsky gave an overview of Atg9 cycling in yeast and
      Shigekazu Nagata talked about apoptosis and engulfment of dead cells by
      macrophages. The meeting consisted of five oral sessions and two poster sessions
      covering a wide range of autophagy-related topics. Exciting unpublished results
      were presented in all sessions, showing how quickly autophagy research is
      progressing. Two themes were discussed in many sessions during the symposium: the
      role of autophagy in the degradation of aggregate-prone proteins and protein
      aggregates, and the possible role of p62 in autophagy.

PMID- 17204841
TI  - Autophagy regulates ageing in C. elegans.
AB  - The role of autophagy in ageing regulation has been suggested based on studies in
      C. elegans, in which knockdown of the expression of bec-1 (ortholog of the yeast
      and mammalian autophagy genes ATG6/VPS30 and beclin 1, respectively) shortens
      lifespan of the daf-2(e1370) mutant C. elegans. However, Beclin1/ATG6 is also
      known to be involved in other cellular functions in addition to autophagy. In the
      current study, we knocked down two other autophagy genes, atg-7 and atg-12, in C.
      elegans using RNAi. We showed that RNAi shortened the lifespan of both wild type
      and daf-2 mutant C. elegans, providing strong support for a role of autophagy in
      ageing regulation.

PMID- 17204842
TI  - Autophagosome-lysosome fusion depends on the pH in acidic compartments in CHO
      cells.
AB  - Autophagy is the bulk degradation of cytoplasmic constituents in response to
      starvation and other environmental or intracellular cues. During this process,
      most of the cytoplasm is sequestered into autophagosomes, which then fuse with
      lysosomes where the degradation of the sequestered material proceeds. We
      investigated the relationship between autophagosome-lysosome fusion and the pH in
      acidic compartments by visualizing the fusion process using fluorescence in CHO
      cells. In this experiment, mitochondria were labeled with GFP by transfecting CHO
      cells with the presequence of ornithine transcarbamylase, and lysosomes were
      labeled with Texas Red Dextran; any fusion was identified by the colocalization
      of mitochondria (in autophagosomes) and lysosomes using fluorescence microscopy.
      When CHO cells were treated with rapamycin or starvation medium to induce
      autophagy, the colocalization of fluorescence was observed. Whereas when they
      were treated with 3-MA, an inhibitor of autophagy, the colocalization
      disappeared. We conclude that the colocalization reflects the fusion of
      autophagosomes and lysosomes. Moreover, when the CHO cells were treated with
      drugs that increase the pH of acidic compartments, the colocalization
      disappeared. This suggests that the autophagosome-lysosome fusion is inhibited by
      increasing pH in acidic compartments independently of V-ATPase activity in CHO
      cells.

PMID- 17204843
TI  - The importance of diversity.

PMID- 17204844
TI  - Nucleus-vacuole junctions and piecemeal microautophagy of the nucleus in S.
      cerevisiae.
AB  - Various modes of autophagy conspire to degrade virtually every compartment of the
      eukaryotic cell. In Saccharomyces cerevisiae, a process called "piecemeal
      microautophagy of the nucleus" (PMN) even pinches off and degrades nonessential
      portions of the nucleus. PMN is a constitutive process induced to high levels by
      starvation or rapamycin, an inhibitor of TOR kinase. PMN occurs at nucleus
      vacuole (NV) junctions, which are Velcro-like patches formed by interactions
      between the vacuole membrane protein Vac8p and the outer-nuclear-membrane protein
      Nvj1p. In response to nutrient depletion, Nvj1p increasingly binds and sequesters
      two proteins with roles in lipid metabolism, Osh1p and Tsc13p. Tsc13p is required
      for the normal biogenesis of PMN vesicles. The sequestration of Osh1p by Nvj1p
      likely serves to negatively regulate the trafficking of tryptophan permease(s) to
      the plasma membrane. Thus, NV junctions and PMN orchestrate novel and
      sophisticated responses to nutrient limitation.

PMID- 17204845
TI  - Autophagy induction and autophagic cell death in effector T cells.
AB  - The population size of the T cells is tightly regulated. The T cell number
      drastically increases in response to their specific antigens. Upon antigen
      clearance, the T cell number decreases over time. Apoptosis, also called type I
      programmed cell death, plays an important role in eliminating T cells. The role
      of autophagic cell death, also called type II programmed cell death, is unclear
      in T cells. Our recent work demonstrated that autophagy is induced in both Th1
      and Th2 cells. Both TCR signaling and IL-2 increase autophagy in T cells, and JNK
      MAP kinases are required for the induction of autophagy in T cells, whereas
      caspases and mTOR inhibit autophagy in T cells. Autophagy is required for
      mediating growth factor withdrawal-dependent cell death in T cells. Here, we
      hypothesize that autophagic cell death plays an important role in T cell
      homeostasis.

PMID- 17204846
TI  - Atg9 trafficking in the yeast Saccharomyces cerevisiae.
AB  - Autophagy can be divided into selective and nonselective modes. This process is
      considered selective when a precise cargo is specifically and exclusively
      incorporated into autophagosomes, the double-membrane vesicles that are the
      hallmark of autophagy. In contrast, during nonselective, bulk autophagy,
      cytoplasmic components are randomly enwrapped into autophagosomes. To date,
      approximately 30 autophagy-related genes called ATG have been identified. Sixteen
      of them compose the general basic machinery catalyzing the formation of double
      membrane vesicles in all eukaryotic cells. The rest of them are often not
      conserved between species and cooperate with the basic Atg proteins during either
      selective or nonselective autophagy. Atg9 is the only integral membrane component
      of the conserved Atg machinery and appears to be a crucial organizational
      element. Recent studies in the S. cerevisiae have shown that Atg9 transport is
      differentially regulated depending on the autophagy mode. In this addendum, we
      will review and discuss what has recently been unveiled about yeast S. cerevisiae
      Atg9 trafficking, its modulators and its potential role in double-membrane
      vesicle biogenesis.

PMID- 17204847
TI  - mTOR kinase and the regulatory subunit of protein kinase A (PRKAR1A) spatially
      and functionally interact during autophagosome maturation.
AB  - The regulatory subunit 1-alpha (RIalpha) of protein kinase A (PKA) and the mTOR
      kinase are involved in a common pathway regulating mammalian autophagy. RIalpha
      was found to localize on Rab7-positive late endosomes and on LC3-positive
      autophagosomal membranes in cultured cells. RIalpha was also shown to physically
      interact with mTOR kinase and affect its phosphorylation and activity. In this
      addendum, we further explore the subcellular distribution of mTOR related to
      RIalpha and LC3. We present experiments showing that mTOR colocalizes with
      RIalpha-, Rab7- and LC3-positive membranes in cultured cells. Because RIalpha
      regulates the phosphorylation and activity of mTOR kinase, which we now show
      localizes on autophagosomal membranes, the possibility emerges that the RIalpha
      mTOR complex acts at the level of autophagosome maturation.

PMID- 17204848
TI  - ATG genes involved in non-selective autophagy are conserved from yeast to man,
      but the selective Cvt and pexophagy pathways also require organism-specific
      genes.
AB  - ATG genes encode proteins that are required for macroautophagy, the Cvt pathway
      and/or pexophagy. Using the published Atg protein sequences, we have screened
      protein and DNA databases to identify putative functional homologs (orthologs) in
      21 fungal species (yeast and filamentous fungi) of which the genome sequences
      were available. For comparison with Atg proteins in higher eukaryotes, also an
      analysis of Arabidopsis thaliana and Homo sapiens databases was included. This
      analysis demonstrated that Atg proteins required for non-selective macroautophagy
      are conserved from yeast to man, stressing the importance of this process in cell
      survival and viability. The A. thaliana and human genomes encode multiple
      proteins highly similar to specific fungal Atg proteins (paralogs), possibly
      representing cell type-specific isoforms. The Atg proteins specifically involved
      in the Cvt pathway and/or pexophagy showed poor conservation, and were generally
      not present in A. thaliana and man. Furthermore, Atg19, the receptor of Cvt
      cargo, was only detected in Saccharomyces cerevisiae. Nevertheless, Atg11, a
      protein that links receptor-bound cargo (peroxisomes, the Cvt complex) to the
      autophagic machinery was identified in all yeast species and filamentous fungi
      under study. This suggests that in fungi an organism-specific form of selective
      autophagy may occur, for which specialized Atg proteins have evolved.

PMID- 17204849
TI  - Crosstalk between Bak/Bax and mTOR signaling regulates radiation-induced
      autophagy.
AB  - Bax and Bak, act as a gateway for caspase-mediated cell death. mTOR, an Akt
      downstream effector, plays a critical role in cell proliferation, growth and
      survival. The inhibition of mTOR induces autophagy, whereas apoptosis is a minor
      cell death mechanism in irradiated solid tumors. We explored possible alternative
      pathways for cell death induced by radiation in Bax/Bak-/- double knockout (DKO)
      MEF cells and wild-type cells, and we compared the cell survival: the Bax/Bak-/-
      cells were more radiosensitive than the wild-type cells. The irradiated cells
      displayed an increase in the pro-autophagic proteins ATG5-ATG12 and Beclin-1.
      These results are surprising in the fact that the inhibition of apoptosis
      resulted in increasing radiosensitivity; indicating that perhaps autophagy is the
      cornerstone in the cell radiation sensitivity regulation. Furthermore,
      irradiation upregulates autophagic programmed cell death in cells that are unable
      to undergo Bax/Bak-mediated apoptosis. We hypothesize the presence of a
      phosphatase-possibly PTEN, an Akt/mTOR negative regulator that can be inhibited
      by Bax/Bak. This fits with our hypothesis of Bax/Bak as a downregulator of
      autophagy. We are currently conducting experiments to explore the relationship
      between apoptosis and autophagy. Future directions in research include strategies
      targeting Bax/Bak in cancer xenografts and exploring novel radiosensitizers
      targeting autophagy pathways.

PMID- 17204850
TI  - Autophagy limits Listeria monocytogenes intracellular growth in the early phase
      of primary infection.
AB  - Autophagy has been recently proposed to be a component of the innate cellular
      immune response against several types of intracellular microorganisms. However,
      other intracellular bacteria including Listeria monocytogenes have been thought
      to evade the autophagic cellular surveillance. Here, we show that cellular
      infection by L. monocytogenes induces an autophagic response, which inhibits the
      growth of both the wild-type and a DeltaactA mutant strain, impaired in cell-to
      cell spreading. The onset of early intracellular growth is accelerated in
      autophagy-deficient cells, but the growth rate once bacteria begin to multiply in
      the cytosol does not change. Moreover, a significant fraction of the
      intracellular bacteria colocalize with autophagosomes at the early time-points
      after infection. Thus, autophagy targets L. monocytogenes during primary
      infection by limiting the onset of early bacterial growth. The bacterial
      expression of listeriolysin O but not phospholipases is necessary for the
      induction of autophagy, suggesting a possible role for permeabilization of the
      vacuole in the induction of autophagy. Interestingly, the growth of a DeltaplcA/B
      L. monocytogenes strain deficient for bacterial phospholipases is impaired in
      wild-type cells, but restored in the absence of autophagy, suggesting that
      bacterial phospholipases may facilitate the escape of bacteria from autophagic
      degradation. We conclude that L. monocytogenes are targeted for degradation by
      autophagy during the primary infection, in the early phase of the intracellular
      cycle, following listeriolysin O-dependent vacuole perforation but preceding
      active multiplication in the cytosol, and that expression of bacterial
      phospholipases is necessary for the evasion of autophagy.

PMID- 17204851
TI  - Immune surveillance via self digestion.
AB  - The adaptive immune system is orchestrated by CD4+ T cells. These cells detect
      peptides presented on Major Histocompatibility Complex (MHC) class II molecules,
      which are loaded in late endosomes with products of lysosomal proteolysis. One
      pathway by which proteins gain access to degradation in lysosomes is
      macroautophagy. We recently showed that constitutive macroautophagy can be
      detected in cells relevant for the immune system, including dendritic cells. In
      these antigen presenting cells, autophagosomes frequently fused with MHC class II
      antigen loading compartments and targeting of Influenza matrix protein 1 (MP1)
      for macroautophagy enhanced MHC class II presentation to MP1-specific CD4+ T cell
      clones up to 20 fold. Our findings indicate that macroautophagy is a constitutive
      and efficient pathway of antigen delivery for MHC class II presentation. We
      suggest that this pathway samples intracellular proteins for immune surveillance
      and induction of tolerance in CD4+ T cells, and could be targeted for improved
      MHC class II presentation of vaccine antigens.

PMID- 17204852
TI  - Permeases recycle amino acids resulting from autophagy.
AB  - Autophagy is a major survival mechanism for eukaryotes to recycle cellular
      nutrients during stress conditions (such as nutrient limitation, or the
      accumulation of damaged organelles). We recently revealed a molecular mechanism
      by which Atg22 recycles amino acids to link the degradative and recycling
      functions of autophagy. Atg22 is not directly required for autophagic body
      breakdown, in contrast to previously reported data. Instead, we found that Atg22,
      Avt3 and Avt4 are partially redundant vacuolar effluxers, which mediate the
      efflux of leucine and other amino acids resulting from autophagy.

PMID- 17204853
TI  - Autophagic elimination of intracellular parasites: convergent induction by IFN
      gamma and CD40 ligation?
AB  - Autophagy has recently been implicated in the immune elimination of the
      intracellular protozoan parasite, Toxoplasma gondii. Toxoplasma and other
      apicomplexan parasites actively invade host cells and form nonfusogenic
      parasitophorous vacuoles. Nevertheless, following entry into IFN-gamma-activated
      effector macrophages, vesiculation of the parasite vacuole or PV membrane ensues,
      in a process dependent upon the activity of p47 GTPases induced by IFN-gamma
      signaling. Subsequent disruption of the plasma membrane of the stripped parasites
      precedes autophagolysosomal elimination of T. gondii. In contrast, ligation of
      the CD40 receptor and autocrine signaling by TNF activate a seemingly distinct,
      p47 GTPase-independent mechanism leading to autophagic elimination of
      intracellular T. gondii, without prior disruption of the pathogen vacuole. Thus,
      two key pathways of the cell-mediated immune response, namely IFN-gamma and
      CD40/CD40L, trigger a common autophagolysosomal endpoint of parasite elimination,
      via distinct intermediary mechanisms.

PMID- 17204854
TI  - Endoplasmic reticulum stress: a new pathway to induce autophagy.
AB  - Autophagy is a response to the stress of nutrient limitation in yeast, whereby
      cytosolic long-lived proteins and organelles are nonselectively degraded, and the
      resulting macromolecules are recycled to allow new protein synthesis that is
      essential for survival. We recently revealed that endoplasmic reticulum (ER)
      stress induces autophagy. When misfolded proteins accumulate in the ER the
      resulting stress activates the unfolded protein response (UPR) to induce the
      expression of chaperones and proteins involved in the recovery process. Under
      conditions of ER stress, the preautophagosomal structure is assembled, and
      transport of autophagosomes to the vacuole is stimulated in an Atg protein
      dependent manner. Interestingly, Atg1 has high kinase activity during ER stress
      induced autophagy similar to the situation in starvation-induced autophagy.

PMID- 17204855
TI  - Regulation of neuronal autophagy in axon: implication of autophagy in axonal
      function and dysfunction/degeneration.
AB  - Autophagy has recently emerged as potential drug target for prevention of
      neurodegeneration. However, the details of autophagy process and regulation in
      the central nervous system (CNS) are unclear. By using a neuronal excitotoxicity
      model mice, we engineered expression of a fluorescent autophagic marker and
      systematically investigated autophagic activity under neurodegenerative
      condition. The study reveals an early response of Purkinje cells to excitotoxic
      insult by induction of autophagy in axon terminals, and that axonal autophagy is
      particularly robust in comparison to the cell body and dendrites. The
      accessibility of axons to rapid autophagy induction suggests local biogenesis of
      autophagosomes in axons. Characterization of functional interaction between
      autophagosome protein LC3 and microtubule-associated protein 1B (MAP1B), which is
      involved in axonal growth, injury and transport provides evidence for neuron or
      axon-specific regulation of autophagosomes. Furthermore, we propose that
      p62/SQSTM1, a putative autophagic substrate can serve as a marker for evaluating
      impairment of autophagic degradation, which helps resolve the controversy over
      autophagy levels under various pathological conditions. Future study of the
      relationship between autophagy and axonal function (e.g., transport) will provide
      insight into the mechanism underlying axonopathy which is directly linked to
      neurodegeneration.

PMID- 17204856
TI  - Autophagy as a mechanism of radiation sensitization in breast tumor cells.
AB  - Current studies to define the mechanism by which vitamin D3 and analogs of
      vitamin D3 enhance the response to ionizing radiation in breast tumor cells
      suggest that these effects are mediated, in large part, through the promotion of
      autophagic cell death. The residual surviving cell population remains in a
      senescent, growth arrested state, with minimal recovery of proliferative
      capacity. It is becoming evident that pathways other than or in addition to
      apoptosis, including senescence arrest, mitotic catastrophe and autophagy,
      contribute to loss of self-renewal capacity in tumor cells exposed to
      chemotherapeutic drugs and ionizing radiation. How and why the cell chooses a
      particular growth arrest and/or cell death pathway remains a puzzle to be solved.

PMID- 17204857
TI  - Naturally occurring, unmodified bacterial toxin for the treatment of glioblastoma
      multiforme?

PMID- 17204859
TI  - Targeting apoptosis to cancer via hTERT promoter.

PMID- 17204860
TI  - Dominant Negative RAS as an anticancer agent.

PMID- 17204861
TI  - Histamine: a potential therapeutic agent for breast cancer treatment?

PMID- 17204862
TI  - Illuminating TRAIL gene therapy.

PMID- 17204863
TI  - The regulation of energy generating metabolic pathways by p53.
AB  - The function of p53 as a tumor suppressor remains undisputed. p53 has a central
      role in cellular stress responses as well as affecting cancer development and
      progression. The word "central", however, is becoming increasingly more of an
      understatement as the list of p53-regulated pathways and processes is ever
      expanding. Although much focus continues to center on p53-mediated signaling
      cascades that control cell growth arrest and/or apoptosis, recent work has begun
      to define a role for p53 in the regulation of metabolic pathways typically
      thought of as essential for maintaining life. With the first potential link
      between p53 and glycolysis reported nearly ten years ago, the topic has gained a
      renewed interest. Recent studies now demonstrate the ability of p53 to regulate
      the expression of several novel genes including PGM (phosphoglycerate mutase),
      TIGAR (TP53-induced glycolysis and apoptosis regulator) and, SCO2 (synthesis of
      cytochrome c oxidase 2), each intimately linked to the processes of glycolysis
      and oxidative phosphorylation. With this discovery, yet another novel means by
      which p53 carries out its tumor suppressor function is brought into light.

PMID- 17204864
TI  - Spontaneous tumor lysis syndrome in acute myeloid leukemia: two cases and a
      review of the literature.
AB  - Spontaneous tumor lysis syndrome (TLS) is a constellation of electrolyte
      abnormalities and acute renal failure, which occurs in the setting of rapid cell
      turnover prior to the administration of cytotoxic chemotherapy. While spontaneous
      TLS is well described in patients with Burkitt's lymphoma, it is thought to occur
      less commonly in other hematologic malignancies. We present two cases of
      spontaneous TLS in patients with newly diagnosed acute myeloid leukemia (AML)
      followed by a review of the literature in this field.

PMID- 17204865
TI  - Evidence of myeloid differentiation in non-M3 acute myeloid leukemia treated with
      the retinoid X receptor agonist bexarotene.
AB  - All-trans-retinoic acid has dramatically changed the treatment paradigm for acute
      promyelocytic leukemia, however, it has no significant activity in non-M3 acute
      myeloid leukemia (AML). In vitro, bexarotene, a retinoid X receptor agonist
      inhibits the proliferation of non-M3 AML cell lines and induces differentiation
      of leukemic blasts from patients. We hypothesized that there may be similar
      activity in patients with AML. We report on two patients with relapsed or
      refractory non-M3 AML treated with bexarotene monotherapy. After initiating
      treatment, both patients showed leukemic differentiation in their peripheral
      blood and reduction in bone marrow blasts to less than 5%. One patient had a
      significant improvement in her platelet count with loss of platelet transfusion
      needs. Differentiation syndrome occurred in one patient and was successfully
      treated with steroids and discontinuation of bexarotene. These data suggest that
      bexarotene has clinical activity in non-M3 AML and may be able to induce myeloid
      differentiation in vivo.

PMID- 17204866
TI  - large-scale serologic testing program to assess the immunogenicity of inactivated
      hepatitis a vaccine (VAQTA) in prefilled syringes following product recall in
      Germany.
AB  - A voluntary recall of VAQTA in prefilled syringes was implemented in Europe in
      late 2001 after the manufacturer noted a slight decrease in the antigen content
      of a small percentage of the syringes manufactured over a particular time frame.
      In Germany, a large-scale serologic testing program was implemented. The assay
      results were conveyed to the subject's physician, and free vaccine was provided
      for anyone requesting revaccination. An analysis was performed on a subset of
      58,546 vaccine recipients with hepatitis A antibody results. Of the 28,681
      persons who received either two 25 units (25 U) or two 50 units (50 U) doses of
      VAQTA, the seropositivity rate (SPR) was 99.5% after receipt of 2 doses, similar
      to the results in prelicensure clinical trials. The SPR was similar among
      recipients of lots that had been manufactured over the time frame associated with
      the recalled lots versus those receiving lots not associated with the recalled
      lots (25U: 99.7% versus 99,7%; 50U: 98.6% versus 99.6%, respectively). There were
      less recipients of 25U doses of the affected lots, who had high hepatitis A
      antibody titers (> or =100 mIU/mL), compared to recipients of unaffected lots.

PMID- 17204867
TI  - Therapeutic vaccination with epidermal growth factor (EGF) in advanced lung
      cancer: analysis of pooled data from three clinical trials.
AB  - We have undertaken the analysis of pooled data from three pilot clinical trials
      of vaccination with Epidermal Growth Factor (EGF) in patients with advanced non
      small cell lung cancer (NSCLC), addressing particularly the issue of the
      relationship between immunization and survival. Eighty-three patients with
      advanced disease were included in three pilot clinical trials and vaccinated with
      the EGF Vaccine. The trials were designed to evaluate the immunogenicity and
      safety of the vaccine using different adjuvants, cyclophosphamide pretreatment or
      not, and different dosage levels of the vaccine. The vaccine elicited specific
      anti-EGF antibody titers in 83% of subjects, and 49% developed a good anti-EGF
      antibody response. The adjuvant, the vaccine dose, and cyclophosphamide
      pretreatment significantly influenced immunogenicity. Patients that seroconverted
      survived significantly longer than patients who did not. Good antibody responders
      survived significantly longer than poor responders. Pooled results from these
      trials confirm that vaccination with EGF is safe and immunogenic in advanced
      NSCLC patients. The association between good antibody responses and survival
      consistently appeared in every single trial independently of the specific trial
      designs. Although these were small pilot nonrandomized clinical trials not
      intended to confirm therapeutic effect, the survival of the pooled patient
      population was statistically greater compared with 163 control patients receiving
      standard treatment.

PMID- 17204868
TI  - Biological feasibility of developing prophylactic vaccines for viral pathogens:
      incubation period as a critical parameter.
AB  - Vaccines for sixteen major human viral pathogens have been approved for use in
      humans. For most other major human viral pathogens, the absence of an efficacious
      prophylactic vaccine is not for lack of effort. To identify the key parameters of
      biologic feasibility that determine "certainty-of-success" for developing
      prophylactic vaccines for major human viral pathogens, basic characteristics of
      viruses, such as primary genomic structure, route of transmission, and durability
      of viral infection were reviewed. These basic characteristics of viruses simply
      do not associate with successful vaccine development, so one must look elsewhere
      for characteristics predictive of successful vaccine development. Herein existing
      data are put forth in a way that demonstrates the impact of the combined effect
      of incubation period and broadly protective, relative immunogenicity on the
      "certainty-of-success" of developing effective vaccines for thirty viral
      pathogens. Both incubation period and broadly protective, relative immunogenicity
      appear to have accounted for much of the past successes in vaccine development,
      and may be useful in predicting where near term successes are most apt to occur.

PMID- 17204870
TI  - Techniques of posterior C1-C2 stabilization.
AB  - Instability of the atlantoaxial complex may result from inflammatory, traumatic,
      congenital, neoplastic, or degenerative disorders and often requires surgical
      stabilization. Initial dorsal wiring techniques allow safe fixation but require
      rigid external immobilization and have been associated with high fusion failure
      rates. Rigid screw fixation techniques including transarticular screw fixation
      and C1-C2 rod-cantilever fixation offer higher fusion rates and less need for
      rigid immobilization but are more technically demanding. C1-C2 fixation using
      crossing C2 laminar screws offers rigid fixation but without the technical
      demands of C2 pars placement. The history and techniques of dorsal fixation of
      the atlantoaxial complex are reviewed, and the success rates and complications of
      each are discussed.

PMID- 17204871
TI  - Use of ventral plates for cervical arthrodesis.
AB  - OBJECTIVE: Ventral cervical plates are used to increase the immediate
      postoperative rigidity of the spine after decompressive and reconstructive
      procedures. The evidence supporting this practice is reviewed. METHODS: A
      computerized literature search of the database of the National Library of
      Medicine was conducted using PubMed. All relevant articles were reviewed and a
      critique was performed to explore the utility of ventral cervical plating.
      RESULTS: Several randomized controlled trials of ventral cervical discectomy
      versus ventral cervical discectomy and fusion were identified. Three randomized
      controlled trials that included a differentiation between anterior cervical
      decompression and fusion, with and without plating, were identified. Many
      retrospective series, technical reports, and topical reviews were also
      identified. CONCLUSION: There is little support in the literature for the medical
      usefulness of ventral cervical plates after single-level cervical fusion. There
      may, however, be a cost-benefit advantage to the use of such devices. In
      multilevel procedures and in the setting of traumatic instability, there seems to
      be an advantage to the use of cervical plates.

PMID- 17204872
TI  - The use of rigid internal fixation in the surgical management of cervical
      spondylosis.
AB  - In the surgical management of cervical spondylosis, the application of rigid
      internal fixation can enhance the immediate stability of the cervical spine. The
      sophistication of such internal fixation systems and the indications for their
      use are continuously evolving. A sound understanding of regional anatomy,
      biomechanics, and kinematics within the cervical spine is essential for the safe
      and effective application of internal fixation. Numerous options currently exist
      for anterior cervical plating systems; some lock the screws to the plate rigidly
      (constrained), whereas others allow for some rotational or translational motion
      between the screw and plate (semiconstrained). The role of anterior fixation in
      single and multilevel fusions is still the subject of some controversy. Long
      anterior cervical reconstructions may require additional posterior fixation to
      reliably promote fusion. Rigid fixation in the posterior cervical spine can be
      achieved with lateral mass screws or pedicle screws. Although lateral mass screws
      provide excellent fixation within the subaxial cervical spine, the regional
      anatomy of C2 and C7 often make it difficult to place such screws, and pedicle
      screws at these levels are advocated. Pedicle screws achieve fixation into both
      the anterior and posterior column and are arguably the most stable form of rigid
      internal fixation within the cervical spine. Familiarity with these internal
      fixation techniques can be an extremely valuable tool for the spine surgeon
      managing these degenerative disorders of the cervical spine.

PMID- 17204873
TI  - Cervical spondylosis: ventral or dorsal surgery.
AB  - Cervical spondylosis is a result of degenerative changes of the cervical spine.
      Neurological symptoms of myelopathy result from the narrowing of the spinal
      canal, causing spinal cord compression. Surgical management of cervical stenosis
      requires an understanding of the interplay between multiple pathological and
      biomechanical factors contributing to this disease process. Surgical
      decompression can be addressed from a ventral, dorsal, or combined approach. The
      authors discuss the technical aspects of the surgical decision making process
      regarding the decision to approach the spine from a ventral or dorsal
      orientation.

PMID- 17204874
TI  - Cervical corpectomy and strut grafting.
AB  - Cervical corpectomy and strut grafting is a deceptively simple procedure that has
      been performed for many years for a variety of cervical spine disorders
      (infection, neoplastic disease, and trauma) but most commonly for cervical
      spondylosis. The procedure requires attention to detail to ensure adequate
      decompression of the neural structures and avoiding injury to the soft tissues of
      the neck and the vertebral artery in the transverse foramina. The following
      description of the technique is one we have successfully used for cervical
      corpectomy and strut grafting. We also discuss patient selection criteria,
      avoidance of common complications, and postoperative management.

PMID- 17204875
TI  - Neurological manifestations of cervical spondylosis: an overview of signs,
      symptoms, and pathophysiology.
AB  - The neurological manifestations of cervical spondylosis include symptomatic
      compression of the spinal cord (myelopathy), nerve roots (radiculopathy), or a
      combination of the two (myeloradiculopathy). The term myeloradiculopathy herein
      defines these often indistinct and inseparable entities. The pathophysiology of
      myeloradiculopathy is multifactorial in nature, and the natural history of
      untreated myeloradiculopathy is not clearly defined. We review the signs,
      symptoms, and clinical findings of cervical myelopathy, radiculopathy, and
      myeloradiculopathy. Standard grading techniques are also reviewed.

PMID- 17204876
TI  - Multiple level discectomy and fusion.
AB  - The ventrolateral approach for surgical decompression of the cervical spine is
      widely used and well known to most spinal surgeons. Because compression of the
      spinal cord and nerve roots usually occurs ventral to the spinal cord, and the
      spinal cord does not tolerate traction, this approach allows safe and direct
      decompression of most compressive pathology. This article reviews the
      indications, diagnostic evaluation, and technique for multiple level discectomy
      and fusion. It further addresses the advantages and disadvantages of this
      technique compared with alternate surgical procedures.

PMID- 17204877
TI  - Cervical laminectomy: technique.
AB  - Spinal canal decompression via cervical laminectomy with or without foraminotomy
      is a mainstay of treatment of cervical spondylotic myelopathy and
      myeloradiculopathy. The goal of this surgery is to expand the cervical canal
      dorsally by removing the spinous processes, laminae, ligamentum flavum, and bony
      hypertrophy that are contributing to the canal stenosis. In selecting this
      particular approach to decompression, the surgeon must take into account the
      spinal geometry and the primary pathology of the patient: an "effective" cervical
      kyphosis is a contraindication to a dorsal approach, and spinal canal compromise
      secondary to ventral compression is best addressed through a ventral or a
      combined ventral and dorsal approach. This technique is technically facile and
      versatile in application. Complications with this procedure are relatively rare,
      with postoperative spinal instability being the primary concern. With proper
      patient selection and attention to surgical technique, laminectomy is a safe and
      effective approach to the management of cervical myelopathy in selected patients.

PMID- 17204878
TI  - Open-door expansile cervical laminoplasty.
AB  - Open-door expansile laminoplasty is a practical surgical technique for the
      treatment of cervical myelopathy secondary to cervical spinal stenosis.
      Laminoplasty procedures were first described in the late 1970s and have undergone
      numerous modifications. The current article reviews the indications, techniques,
      and outcome data for cervical laminoplasty. Complications of laminoplasty and
      comparison to laminectomy outcomes are also discussed.

PMID- 17204879
TI  - Minimally invasive surgery for the management of cervical spondylosis.
AB  - Dorsal surgical procedures have a well-established role in the treatment of both
      radiculopathy and myelopathy caused by cervical spondylosis. Laminectomy and
      laminoplasty procedures can both lead to postoperative kyphosis because of the
      removal of the dorsal supporting structures of the neck. Minimally invasive or
      minimal-access spinal surgery procedures of the dorsal cervical spine are
      evolving techniques with the goal of decompressing the neural structures with
      minimal disruption of the dorsal supporting structures. We think that this will
      lead to less postoperative pain and a decreased incidence of post-decompression
      kyphotic deformity. Patient selection, techniques, and results are discussed for
      both minimally invasive cervical laminoforaminotomy and stenosis decompression.

PMID- 17204880
TI  - Decision making process: problem-based decision making.
AB  - Clinical problems are often complex. Problems of great complexity are usually
      associated with a commensurately greater degree of difficulty with respect to the
      decision making process. This is most certainly true regarding the management of
      cervical spondylosis. Usually, clinicians make clinically appropriate decisions.
      However, more often than realized, suboptimal decisions may be made. Therefore,
      an assessment of the types of errors regarding clinical decision making are
      worthy of consideration. In this article, a scheme for decision making regarding
      the management of cervical spondylosis is presented.

PMID- 17204881
TI  - Mechanical neck pain and cervicogenic headache.
AB  - Mechanical neck pain is a very common symptom that may occur with cervical
      spondylosis. It can be associated with cervical radiculopathy and myelopathy or
      can occur in isolation. Neck pain can result from a variety of causes, including
      trauma, tumor, infection, and degeneration. The presentation of axial neck pain
      varies. This article highlights the presentation, differential diagnosis, and
      appropriate work-up for the patient who presents with mechanical neck pain.

PMID- 17204882
TI  - Cervical radiculopathy: pathophysiology, presentation, and clinical evaluation.
AB  - Cervical radiculopathy is a common condition that usually results from
      compression and inflammation of the cervical nerve root or roots in the region of
      the neural foramen. It is frequently caused by cervical disc herniation and
      cervical spondylosis. The diagnosis can be established by history and physical
      examination, but care should be taken, as diagnoses can mimic or coexist with
      cervical radiculopathy, such as entrapment neuropathies. The pathophysiology,
      presentation, and clinical evaluation of cervical radiculopathy are discussed.

PMID- 17204884
TI  - Cervical spondylotic myelopathy: a brief review of its pathophysiology, clinical
      course, and diagnosis.
AB  - Degenerative disease of the cervical spine commonly occurs in the natural process
      of aging. This can lead to compression of the spinal cord and symptomatic
      myelopathy. We review the pathophysiological factors that lead to myelopathy and
      the controversial natural history of untreated myelopathy. Signs and symptoms at
      presentation, examination findings, differential diagnosis, and diagnostic
      studies are also discussed.

PMID- 17204885
TI  - Medical management of cervical spondylosis.
AB  - Medical management is often the initial management of cervical spondylitic
      syndromes, including radiculopathy, myelopathy, and neck pain. This includes
      pharmacological and rehabilitation treatment. Prospective studies comparing the
      efficacy of surgical versus medical management are lacking. The indications and
      efficacy of pharmacological and rehabilitative treatments are reviewed. The use
      of anti-inflammatory drugs, muscle relaxants, analgesics, antidepressants,
      anticonvulsants, steroids, facet joint ablation, and physical therapy are
      reviewed. A rationale for the medical management of acute neck pain, chronic neck
      pain, radiculopathy, and myelopathy is presented.

PMID- 17204886
TI  - Surgery for neck pain.
AB  - Axial neck pain is a common finding that typically represents a spectrum of
      clinical Arlington Orthopedic Associates, disorders affecting the cervical spine.
      Controversy exists concerning the ultimate treatment of the patient who presents
      with cervical spondylosis and primarily axial neck pain without radicular
      symptoms or myelopathy and who has failed to respond to extensive nonoperative
      treatment methods. Cervical discography has been used to assist in determining
      the specific level or levels causing the neck pain and, potentially, which levels
      to fuse; however, controversy regarding the specificity of cervical discograms
      has also been debated in the literature. Los Angeles, California We recommend
      exhausting all conservative means of treatment of axial neck pain. Surgery is
      offered only after conservative treatment fails and appropriate psychological
      testing is performed, as well as diagnostic imaging and discography that confirm
      a specific level or levels as the pain source. Cervical fusion may demonstrate
      good results in appropriately chosen patients with cervical spondylosis and axial
      neck pain.

PMID- 17204887
TI  - Posterior cervical spine surgery for radiculopathy.
AB  - It is now common knowledge that cervical radiculopathy, frequently caused by disc
      herniation and/or degeneration, will often improve without surgical intervention.
      Only a small percentage of patients with the severity of symptoms necessitate
      surgical treatment. Surgery for radiculopathy is indicated for motor weakness,
      progressive neurological deficits, and progressive symptoms that do not improve
      with nonoperative treatment. Advantages and disadvantages exist for both ventral
      and dorsal approaches in the surgical treatment of cervical radiculopathy.
      Indications and results for dorsal nerve root decompression are discussed, and a
      review of our preferred techniques, including use of minimally invasive
      technology, is presented.

PMID- 17204888
TI  - Anterior cervical approach for the treatment of cervical myelopathy.
AB  - Compression of the spinal cord by the degenerating cervical spine tends to lead
      to progressive clinical symptoms over a variable period of time. Surgical
      decompression can stop this process and lead to recovery of function. The choice
      of surgical technique depends on what is causing the compression of the spinal
      cord. This article reviews the symptoms and assessment for cervical spondylotic
      myelopathy (clinically evident compression of the spinal cord) and discusses the
      indications for decompression of the spinal cord anteriorly.

PMID- 17204889
TI  - Cervical spondylosis anatomy: pathophysiology and biomechanics.
AB  - Cervical spondylosis is the most common progressive disorder in the aging
      cervical spine. It results from the process of degeneration of the intervertebral
      discs and facet joints of the cervical spine. Biomechanically, the disc and the
      facets are the connecting structures between the vertebrae for the transmission
      of external forces. They also facilitate cervical spine mobility. Symptoms
      related to myelopathy and radiculopathy are caused by the formation of
      osteophytes, which compromise the diameter of the spinal canal. This compromise
      may also be partially developmental. The developmental process, together with the
      degenerative process, may cause mechanical pressure on the spinal cord at one or
      multiple levels. This pressure may produce direct neurological damage or ischemic
      changes and, thus, lead to spinal cord disturbances. A thorough understanding of
      the biomechanics, the pathology, the clinical presentation, the radiological
      evaluation, as well as the surgical indications of cervical spondylosis, is
      essential for the management of patients with cervical spondylosis.

PMID- 17204890
TI  - Dorsal surgery for myelopathy and myeloradiculopathy.
AB  - OBJECTIVE: To review the dorsal approaches to the cervical spine for myelopathy
      and myeloradiculopathy. METHODS: The literature was reviewed in reference to
      dorsal approaches for cervical myelopathy and myeloradiculopathy. RESULTS: There
      are a variety of surgical approaches in the management of cervical myelopathy and
      myeloradiculopathy. Deciding which is the best method for any individual requires
      the surgeon to be aware of the advantages of each technique, as well as the
      complications and limitations of each approach. CONCLUSION: Laminectomy is the
      traditional technique used for multilevel cervical stenosis. The complications
      related to laminectomy, such as late neurological decline, kyphosis, instability,
      and postoperative radiculopathy, led to laminectomy with fusion. In Japan,
      dissatisfaction with both laminectomy and laminectomy with fusion led to the
      development of laminoplasty for dorsal treatment of multilevel cervical stenosis.
      This article highlights the salient features of preoperative evaluation in this
      patient population as it pertains to dorsal surgical approaches. Additionally,
      the techniques of laminectomy, laminectomy with fusion, and laminoplasty are
      compared, and the results are reviewed.

PMID- 17204891
TI  - Combined ventral and dorsal surgery for myelopathy and myeloradiculopathy.
AB  - The past decade has witnessed significant advances in the surgical treatment of
      cervical myelopathy and myeloradiculopathy. In this article, we discuss in detail
      the indications for combined ventral and dorsal surgery for the treatment of
      cervical myelopathy and myeloradiculopathy. In addition, the advances in surgical
      technique and instrumentation in cervical spine surgery are explored. Finally,
      complication avoidance and management strategies are discussed. Combined ventral
      and dorsal decompression, reconstruction, and instrumentation procedures are
      viable options in the treatment of a select group of patients with complex
      cervical myelopathy or myeloradiculopathy.

PMID- 17204892
TI  - Cervical deformity correction.
AB  - Subaxial cervical deformities most often occur in the sagittal plane, primarily
      as kyphosis. Kyphosis may develop secondary to advanced degenerative disease,
      trauma, neoplastic disease, or after surgery. Whatever the cause, the development
      of cervical deformity should be avoided and corrected when appropriate because
      the greater the deformity, the greater the probability of an associated
      neurological deficit or chronic pain. Patients usually present with mechanical
      type cervical pain, with or without neurological deficit (i.e., myelopathy). They
      may also be relatively asymptomatic. Work-up includes appropriate imaging
      studies, such as radiographs, including dynamic images, and magnetic resonance
      imaging or computed tomography myelography. The deformity may be accurately
      assessed and an appropriate surgical strategy undertaken. Depending on
      flexibility of the deformity and the presence or absence of facet ankylosis, a
      dorsal, ventral, or combined approach may be used. All approaches are unique in
      their ability to correct a deformity and in their associated complications. A
      comprehensive discussion of each is undertaken.

PMID- 17204893
TI  - The decision-making process: allograft versus autograft.
AB  - The decision whether to use allograft or autograft in ventral cervical fusions
      has been widely discussed. The literature includes several prospective randomized
      trials. Extensive clinical evidence indicates that autograft use results in
      increased arthrodesis rates and less graft collapse. However, autograft harvest
      has a substantial morbidity rate. Allografts avoid the morbidity associated with
      autograft harvest but result in decreased arthrodesis rates and increased graft
      collapse rates. The decreased arthrodesis rate associated with allografts becomes
      more significant in multilevel surgery and in patients who smoke. The
      introduction and use of ventral cervical plates have made allograft use more
      attractive by increasing arthrodesis rates and decreasing graft collapse.

PMID- 17204895
TI  - Estimates of basilar-membrane nonlinearity effects on masking of tones and
      speech.
AB  - OBJECTIVE: The aim of this experiment was to assess the contribution of cochlear
      nonlinearities to speech recognition in noise for individuals with normal hearing
      and a range of quiet thresholds. For signals close to the characteristic
      frequency (CF) of a place on the basilar membrane, the normal growth of response
      of the basilar membrane is linear at lower signal levels and compressed at medium
      to higher signal levels. In contrast, at moderate to high CFs, the basilar
      membrane responds more linearly to stimuli at frequencies well below the CF
      regardless of input level. Thus, for moderate-level speech and a lower frequency
      masker, the response to the masker grows linearly whereas the response to the
      speech is compressed, which may result in changes in the effectiveness of the
      masker on speech recognition with increases in masker level. To test this
      hypothesis, observed speech-recognition scores were compared with scores
      predicted using an audibility-based model, which did not include nonlinear
      effects that may influence masker effectiveness. DESIGN: Growth of simultaneous
      masking was measured for moderate-level bandpass-filtered nonsense syllables and
      for 350-msec pure tones at frequencies within the speech passband. Masker
      frequencies were within (on-frequency) or below (off-frequency) the speech
      passband. Estimates of basilar-membrane nonlinearities were derived from growth
      of-masking functions for 10-msec, 2.0- and 4.0-kHz tones in narrowband, off
      frequency maskers presented simultaneously. Subjects were 26 adults with normal
      hearing with approximately a 20-dB range of average quiet thresholds. RESULTS:
      Breakpoints (i.e., the levels corresponding to the transitions from linear to
      nonlinear responses) were strongly associated with quiet thresholds but slopes
      measured above the breakpoints were independent of quiet thresholds. Individual
      differences were substantially larger for off-frequency masking of pure tones and
      speech than for on-frequency masking of pure tones and speech. Using an
      audibility-based predictive model, the change in speech audibility resulting from
      the compressed response to speech with increasing off-frequency masker level (and
      the resulting decline in scores) was well predicted from nonlinear growth of
      masking for pure tones measured in the same off-frequency masker. However,
      absolute speech-recognition predictions were generally inaccurate and were a
      function of how well pure-tone signal levels at masked threshold estimated masker
      effectiveness for speech. That is, subjects with lower off-frequency masked
      thresholds had less accurate predictions of speech recognition in off-frequency
      maskers. CONCLUSIONS: Large individual differences in off-frequency masking of
      pure tones and speech are consistent with the assumption that small changes in
      the shape of the basilar-membrane input-output function result in large changes
      in the amount of off-frequency masking but small (if any) changes in on-frequency
      masking where the signal and masker are subject to a similar compression. Growth
      of off-frequency masking of pure tones and speech were correlated with each
      other, consistent with the underlying basilar-membrane response, and consistent
      with changes in breakpoints for subjects with normal hearing and a range of quiet
      thresholds. These results provide support for a role of nonlinear effects in the
      understanding of speech in noise.

PMID- 17204896
TI  - Effect of intratympanic application of aminoglycosides on click-evoked myogenic
      potentials in Guinea pigs.
AB  - OBJECTIVES: Although numerous studies have identified damage to the cochlear and
      vestibular end organs as the primary site of aminoglycoside-induced ototoxicity,
      the effect on the saccule remains poorly understood, possibly due to lack of
      monitoring saccular function in experimental animals. Therefore, this study
      applied three kinds of aminoglycosides into the tympanic space of guinea pigs to
      examine their toxic impact on the saccule by way of click-evoked myogenic
      potential test coupled with morphologic assessment. DESIGN: Albino guinea pigs
      were treated with saline, gentamicin, tobramycin, or amikacin, with 10 animals
      assigned to each group. Each compound was injected directly overlying but not
      through the round window membrane on the left ear, with the right ear serving as
      a control. One week after injection, each animal underwent auditory brain stem
      response, caloric test, and click-evoked myogenic potential test. Animals were
      then killed for morphologic assessment through the use of light and electron
      microscopic examinations. RESULTS: The animals treated with saline, gentamicin,
      tobramycin, or amikacin exhibited abnormal auditory brain stem response in 0%,
      30%, 100%, and 30% of cases; abnormal caloric responses were found in 0%, 100%,
      40%, and 40% of cases; absent click-evoked myogenic potentials were found in 0%,
      100%, 30%, and 40% of cases, respectively. Gentamicin and other groups differed
      significantly in abnormal rates of caloric responses and click-evoked myogenic
      potentials. Morphologic study of the gentamicin-treated animals confirmed that
      the absence of click-evoked myogenic potential originated from the lesion in the
      saccular macula. CONCLUSIONS: Gentamicin represents the dominant susceptibility
      of aminoglycoside-induced vestibulotoxicity for eliminating both semicircular
      canal and saccular functions. This study further confirms the findings of human
      studies in which the caloric and vestibular evoked myogenic potentials responses
      were monitored to assess the abolition of vestibular function in patients treated
      with intratympanic gentamicin injection.

PMID- 17204897
TI  - Predictive measures of directional benefit part 1: estimating the directivity
      index on a manikin.
AB  - OBJECTIVE: In this investigation, a method for computing a directivity index (DI)
      on a manikin for directional microphones in hearing aids was proposed and
      evaluated comparatively to other conventional methods. DESIGN: Test devices
      included first- and second-order directional microphones. Signal presentation,
      implemented in an anechoic chamber, involved a single noise source rotated
      completely around the directional microphone in a hearing aid, in free field and
      on a manikin, at a defined radius. The area covered was equivalent to the
      approximate surface area of a sphere. It was anticipated that an equal angular
      resolution of 10 degrees (elevation and azimuth) would effectively estimate the
      DI of first-, second-, and higher-order directional microphone systems located in
      a hearing aid on a manikin. A total of 450 spatially varied presentation points
      were analyzed, each weighted in reference to direction of arrival on the
      directional microphone. RESULTS: Empiric differences between the DI derived from
      the 3D-DI method proposed in this investigation and the conventionally derived 2D
      DI method DI on a manikin were as large as 3.8 dB in the higher frequencies,
      depending on the device under test. CONCLUSIONS: The magnitude of these
      differences was dependent on the device under test microphone location. The
      further the microphone was placed into the ear of the manikin, the larger the
      empiric differences.

PMID- 17204898
TI  - Predictive measures of directional benefit part 2: verification of different
      approaches to estimating directional benefit.
AB  - OBJECTIVE: In this investigation, the relation between various directivity
      measures and subject performance with directional microphone hearing aids was
      determined. DESIGN: Test devices included first- and second-order directional
      microphones. Recordings of sentences and noise (Hearing in Noise Test, HINT) were
      made through each test device in simple, complex, and anisotropic background
      noise conditions. Twenty-six subjects, with normal hearing, were administered the
      HINT test recordings and directional benefit was computed. These measures were
      correlated to theoretical, free-field, and Knowles Electronic Manikin for
      Acoustic Research (KEMAR) directivity index (DI) values, as well as front-to-back
      ratios (FBR), in situ signal-to-noise ratios (SNR), and a newly proposed Db SNR,
      wherein a predictive value of the SNR improvement is calculated as a function of
      the noise source incidence. RESULTS: The different predictive scores showed high
      correlation to the measured directional benefit scores in the complex (diffuse
      like) background noise condition (r = 0.89 to 0.97, p < 0.05) but not across all
      background noise conditions (r = 0.45 to 0.97, p < 0.05). The Db SNR approach and
      the in situ SNR measures provided excellent prediction of subject performance in
      all background noise conditions (0.85 to 0.97, p < 0.05). None of the predictive
      measures could account for the effects of reverberation on the speech signal (r =
      0.35 to 0.40, p < 0.05). CONCLUSIONS: For environments that included a discrete
      number of noise sources, the in situ SNR and Db SNR estimates were most
      predictive of subject performance. No predictive approach was indicative of the
      directional benefit achieved when the speech was also subjected to reverberation
      (temporal distortion). This finding has implications for real-world estimates of
      directional benefit.

PMID- 17204899
TI  - Speech understanding in background noise with the two-microphone adaptive
      beamformer BEAM in the Nucleus Freedom Cochlear Implant System.
AB  - OBJECTIVE: This paper evaluates the benefit of the two-microphone adaptive
      beamformer BEAM in the Nucleus Freedom cochlear implant (CI) system for speech
      understanding in background noise by CI users. DESIGN: A double-blind evaluation
      of the two-microphone adaptive beamformer BEAM and a hardware directional
      microphone was carried out with five adult Nucleus CI users. The test procedure
      consisted of a pre- and post-test in the lab and a 2-wk trial period at home. In
      the pre- and post-test, the speech reception threshold (SRT) with sentences and
      the percentage correct phoneme scores for CVC words were measured in quiet and
      background noise at different signal-to-noise ratios. Performance was assessed
      for two different noise configurations (with a single noise source and with three
      noise sources) and two different noise materials (stationary speech-weighted
      noise and multitalker babble). During the 2-wk trial period at home, the CI users
      evaluated the noise reduction performance in different listening conditions by
      means of the SSQ questionnaire. In addition to the perceptual evaluation, the
      noise reduction performance of the beamformer was measured physically as a
      function of the direction of the noise source. RESULTS: Significant improvements
      of both the SRT in noise (average improvement of 5-16 dB) and the percentage
      correct phoneme scores (average improvement of 10-41%) were observed with BEAM
      compared to the standard hardware directional microphone. In addition, the SSQ
      questionnaire and subjective evaluation in controlled and real-life scenarios
      suggested a possible preference for the beamformer in noisy environments.
      CONCLUSIONS: The evaluation demonstrates that the adaptive noise reduction
      algorithm BEAM in the Nucleus Freedom CI-system may significantly increase the
      speech perception by cochlear implantees in noisy listening conditions. This is
      the first monolateral (adaptive) noise reduction strategy actually implemented in
      a mainstream commercial CI.

PMID- 17204900
TI  - Sound-direction identification with bilateral cochlear implants.
AB  - OBJECTIVE: The purpose of this study was to compare the accuracy of sound
      direction identification in the horizontal plane by bilateral cochlear implant
      users when localization was measured with pink noise and with speech stimuli.
      DESIGN: Eight adults who were bilateral users of Nucleus 24 Contour devices
      participated in the study. All had received implants in both ears in a single
      surgery. Sound-direction identification was measured in a large classroom by
      using a nine-loudspeaker array. Localization was tested in three listening
      conditions (bilateral cochlear implants, left cochlear implant, and right
      cochlear implant), using two different stimuli (a speech stimulus and pink noise
      bursts) in a repeated-measures design. RESULTS: Sound-direction identification
      accuracy was significantly better when using two implants than when using a
      single implant. The mean root-mean-square error was 29 degrees for the bilateral
      condition, 54 degrees for the left cochlear implant, and 46.5 degrees for the
      right cochlear implant condition. Unilateral accuracy was similar for right
      cochlear implant and left cochlear implant performance. Sound-direction
      identification performance was similar for speech and pink noise stimuli.
      CONCLUSIONS: The data obtained in this study add to the growing body of evidence
      that sound-direction identification with bilateral cochlear implants is better
      than with a single implant. The similarity in localization performance obtained
      with the speech and pink noise supports the use of either stimulus for measuring
      sound-direction identification.

PMID- 17204901
TI  - Effects of bone oscillator coupling method, placement location, and occlusion on
      bone-conduction auditory steady-state responses in infants.
AB  - OBJECTIVE: The aim of these experiments was to investigate procedures used when
      estimating bone-conduction thresholds in infants. The objectives were: (i) to
      investigate the variability in force applied using two common bone-oscillator
      coupling methods and to determine whether coupling method affects threshold
      estimation, (ii) to examine effects of bone-oscillator placement on bone
      conduction ASSR thresholds, and (iii) to determine whether the occlusion effect
      is present in infants by comparing bone-conduction ASSR thresholds for unoccluded
      and occluded ears. DESIGN: Experiment 1A: The variability in the amount of force
      applied to the bone oscillator by trained assistants (n = 4) for elastic-band and
      hand-held coupling methods was measured. Experiment 1B: Bone-conduction
      behavioral thresholds in 10 adults were compared for two coupling methods.
      Experiment 1C: ASSR thresholds and amplitudes to multiple bone-conduction stimuli
      were compared in 10 infants (mean age: 17 wk) using two coupling methods.
      Experiment 2: Bone-conduction ASSR thresholds and amplitudes were compared for
      temporal, mastoid and forehead oscillator placements in 15 preterm infants (mean
      age: 35 wk postconceptual age (PCA)). Experiment 3: Bone-conduction ASSR
      thresholds, amplitudes and phase delays were compared in 13 infants (mean age: 15
      wk) for an unoccluded and occluded test ear. All infants that participated had
      passed a hearing screening test. RESULTS: Experiment 1A: Coupling method did not
      significantly affect the variability in force applied to the oscillator.
      Experiment 1B: There were no differences in adult bone-conduction behavioural
      thresholds between coupling methods. Experiment 1C: There was no significant
      difference between oscillator coupling method or significant frequency x coupling
      method interaction for ASSR thresholds or amplitudes in the young infants tested.
      However, there was a nonsignificant 9-dB better threshold at 4000 Hz for the
      elastic-band method. Experiment 2: Mean bone-conduction ASSR thresholds for the
      preterm infants were not significantly different for the temporal and mastoid
      placements. Mean ASSR thresholds for the forehead placement were significantly
      higher compared to the other two placements (12-18 dB higher on average). Mean
      ASSR amplitudes were significantly larger for the temporal and mastoid placements
      compared to the forehead placement. Experiment 3: There was no difference in mean
      ASSR thresholds, amplitudes or phase delays for the unoccluded versus occluded
      conditions. CONCLUSIONS: Trained assistants can apply an appropriate amount of
      force to the bone oscillator using either the elastic-band or hand-held method.
      Coupling method has no significant effect on estimation of bone-conduction
      thresholds; therefore, either may be used clinically provided assistants are
      appropriately trained. For preterm infants, there are no differences in ASSRs
      when the oscillator is positioned at the temporal or mastoid placement. However,
      thresholds are higher and amplitudes are smaller for the forehead placement,
      consequently, a forehead placement should be avoided for clinical testing. There
      does not appear to be a significant occlusion effect in young infants; therefore,
      it may be possible to do bone-conduction testing with ears unoccluded or occluded
      without applying a correction factor, although further research is needed to
      confirm this finding.

PMID- 17204902
TI  - Evaluation of the benefit for cochlear implantees of two assistive directional
      microphone systems in an artificial diffuse noise situation.
AB  - OBJECTIVE: People with cochlear implants have severe problems with speech
      understanding in noisy surroundings. This study evaluates and quantifies the
      effect of two assistive directional microphone systems compared to the standard
      headpiece microphone on speech perception in quiet surroundings and in background
      noise, in a laboratory setting developed to reflect a situation whereby the
      listener is disturbed by a noise with a mainly diffuse character due to many
      sources in a reverberant room. DESIGN: Thirteen postlingually deafened patients,
      implanted in the Leiden University Medical Centre with the Clarion CII device,
      participated in the study. An experimental set-up with 8 uncorrelated steady
      state noise sources was used to test speech perception on monosyllabic words.
      Each subject was tested with a standard headpiece microphone, and the two
      assistive directional microphones, TX3 Handymic by Phonak and the Linkit array
      microphone by Etymotic Research. Testing was done in quiet at a level of 65 dB
      SPL and with decreasing signal-to-noise ratios (SNR) down to -15 dB. RESULTS:
      Using the assistive directional microphones, speech recognition in background
      noise improved substantially and was not affected in quiet. At an SNR of 0 dB,
      the average CVC scores improved from 45% for the headpiece microphone to 67% and
      62% for the TX3 Handymic and the Linkit respectively. Compared to the headpiece,
      the Speech Reception Threshold (SRT) improved by 8.2 dB SNR and 5.9 dB SNR for
      the TX3 Handymic and the Linkit respectively. The gain in SRT for TX3 Handymic
      and Linkit was neither correlated to the SRT score with headpiece nor the
      duration of CI-use. CONCLUSION: The speech recognition test in background noise
      showed a clear benefit from the assistive directional microphones for cochlear
      implantees compared to the standard microphone. In a noisy environment, the
      significant benefit from these assistive device microphones may allow
      understanding of speech with greater ease.

PMID- 17204903
TI  - Categorical Perception of Speech (VOT) and Analogous Non-Speech (FOT) signals:
      Behavioral and electrophysiological correlates.
AB  - OBJECTIVE: To determine whether voicing perception is influenced primarily by
      linguistic experience or if it is due to innate temporal sensitivity to voicing
      boundaries, by examining behavioral and electrophysiological correlates of speech
      Voice-Onset-Time (VOT) and nonspeech Formant-Onset-Time (FOT) categorical
      perception. DESIGN: Behavioral measures and auditory event-related potentials
      (ERPs) were obtained from 14 normal-hearing Hebrew speakers, whose voicing
      distinction is different than English, during identification and discrimination
      of two sets of stimuli: a VOT continuum, created by editing natural productions
      of /ba/ and /pa/, and an analogous nonspeech continuum, composed of two
      synthesized formants, varying in their onset time-FOT. RESULTS: VOT and FOT
      continua yielded similar behavioral identification curves. Differences between
      the two stimulus types were found in discrimination of within-category
      differences and in reaction time effects. During identification and
      discrimination tasks, ERPs were differently affected by the VOT or FOT value of
      the stimulus: VOT value had a significant effect on N1 latency and on N1 and P2
      amplitudes whereas FOT value had a significant effect on P2 amplitude.
      Additionally, during identification tasks, whereas all speech signals evoked a
      P3, regardless of overt categorization, only the perceptually "rare" nonspeech
      stimulus (+15 msec FOT) evoked a P3. CONCLUSIONS: Voicing boundaries corresponded
      to Hebrew VOT values of production, suggesting that voicing perception in Hebrew
      is mediated mainly by linguistic experience rather than by innate temporal
      sensitivity. ERP data differed to VOT versus FOT stimuli as early as N1,
      indicating that brain processing of the temporal aspects of speech and nonspeech
      signals differ from their early stages. Further studies to establish the neural
      response patterns to voicing in speakers of languages that use different voicing
      categories than English are warranted.

PMID- 17204904
TI  - Combined effects of low-dose spironolactone and captopril therapy in a rat model
      of genetic hypertrophic cardiomyopathy.
AB  - For several years, the severe side effects associated with the use of high doses
      of the aldosterone antagonist, spironolactone, limited its clinical use. Studies
      have recently shown efficacy and minimal side effects of low-dose spironolactone
      combined with standard therapy in the treatment of heart failure and hypertensive
      patients. The authors evaluated the effects of low-dose spironolactone alone or
      in combination with angiotensin-converting enzyme (ACE) inhibitors on the
      progression of left ventricular dysfunction and remodeling in a congenic rat
      model of hypertrophic cardiomyopathy. The congenic SS-16/Mcwi rats developed
      severe cardiac hypertrophy despite being normotensive even on high-salt diet. SS
      16/Mcwi and SS/Mcwi rats were fed a low-salt (0.4% NaCl) diet and were treated
      with vehicle (CON), spironolactone (20 mg/kg/d subcutaneously), captopril (100
      mg/kg/d drinking water), or both spironolactone and captopril for 4 weeks. Blood
      pressure, plasma peptides, cardiac fibrosis, and echocardiography measurements
      were evaluated. Spironolactone at a low dose had no effect on blood pressure,
      cardiac hypertrophy, and fibrosis in either strain. However, in combination with
      captopril, spironolactone decreased the cardiac hypertrophy more than captopril
      treatment alone. In the SS-16/Mcwi rats, the combined therapy significantly
      preserved the cardiac index when compared with control. These data indicate that
      the addition of low-dose spironolactone to captopril treatment was more effective
      in preventing the progression of heart hypertrophy and ventricular dysfunction in
      the SS-16/Mcwi than captopril alone. This study suggests that combined
      spironolactone and captopril therapy may be useful in the treatment of
      hypertrophic cardiomyopathy.

PMID- 17204905
TI  - Prevention of life-threatening ventricular tachyarrhythmia by a novel and pure
      class-III agent, nifekalant hydrochloride.
AB  - Nifekalant hydrochloride (NIF) is a novel intravenous class-III antiarrhythmic
      agent with a pirimidinedione structure that purely blocks the K+ channel without
      inhibiting beta-adrenergic receptors. The authors investigated the efficacy of
      NIF for refractory ventricular tachycardia/fibrillation (VT/VF). They studied 30
      patients treated with an intravenous infusion of NIF [ 26 men, 4 women; age: 63
      +/- 17 (mean +/- SD) years] at a dose of 0.19 +/- 0.14 mg/kg body weight per
      hour. Sixteen were patients with acute coronary syndrome (ACS), and 14 were
      patients with chronic structural heart disease (Chr-HD). Amiodarone and sotalol
      had already been administered to 9 patients with Chr-HD before the administration
      of NIF. The QT and T peak-end (Tp-e) intervals were measured and corrected by
      Bazett's method (QTc, cTp-e). The left ventricular ejection fraction was
      depressed (28 +/- 9%). NIF was effective for preventing VT/VF without
      proarrhythmia and hemodynamic deterioration in 21 patients (70%; 12 with ACS; 9
      with Chr-HD), but ineffective in 4 patients (all with Chr-HD). The QTc
      prolongation in the responders was more pronounced than in the nonresponders (25%
      +/- 15% versus 5% +/- 7% increase; P < 0.05). Proarrhythmic torsade de pointes
      (TdP) developed transiently in the remaining 5 patients in whom the cTp-e was
      markedly increased compared with that in the responders (93% +/- 49% versus 37%
      +/- 41% increase; P < 0.05). In conclusion, these findings indicate that the
      intravenous administration of NIF is useful in the emergent treatment of
      inhibiting drug-refractory VT/VF, although proarrhythmic TdP owing to an
      enhancement of transmural dispersion of repolarization needs to be taken into
      account.

PMID- 17204906
TI  - Long-term inhibition of Rho-kinase ameliorates hypoxia-induced pulmonary
      hypertension in mice.
AB  - Pulmonary hypertension (PH) is a fatal disease characterized by endothelial
      dysfunction, hypercontraction and proliferation of vascular smooth muscle cells,
      and migration of inflammatory cells for which no satisfactory treatment has yet
      been developed. It has been recently demonstrated that Rho-kinase, an effector of
      the small GTPase Rho, is involved in the pathogenesis of arteriosclerosis and
      that long-term inhibition of Rho-kinase markedly ameliorates monocrotaline
      induced PH in rats. However, it remains to be examined whether direct inhibition
      of Rho-kinase also ameliorates PH with a different etiology and whether
      endothelial nitric oxide synthase (eNOS) is involved in the beneficial effects of
      Rho-kinase inhibition. This study was designed to address those 2 important
      issues in a hypoxia-induced PH model using wild-type (WT) and eNOS-deficient
      (eNOS) mice. Long-term blockade of Rho-kinase with fasudil (100 mg/kg/d) for 3
      weeks markedly improved PH and right ventricular hypertrophy in WT mice with a
      lesser but significant inhibition noted in eNOS mice. Fasudil upregulated eNOS
      with increased Akt phosphorylation in WT but not in eNOS mice. These results
      suggest that long-term inhibition of Rho-kinase also ameliorates hypoxia-induced
      PH in mice, for which eNOS activation may partially be involved.

PMID- 17204907
TI  - Effects of tacrolimus or sirolimus on proliferation of vascular smooth muscle and
      endothelial cells.
AB  - Local strategies directed against vascular smooth muscle cell (VSMC)
      proliferation such as drug-eluting stents reduce the occurrence of restenosis.
      However, these approaches may also inhibit endothelial cell (EC) proliferation
      and, thus, impair reendothelialization. We compared the effects of tacrolimus on
      human VSMC and EC proliferation and migration to sirolimus, a compound with
      similar molecular structure. Thymidine incorporation was determined in growth
      factor-stimulated VSMC and EC. The drug concentration at which maximal VSMC
      proliferation was inhibited by 50% (IC50) was about 10-fold higher for tacrolimus
      (3.8 x 10 M) than for sirolimus (4.1 x 10 M; P = 0.055). It is interesting that
      the molar IC50 value in EC was around 10-fold higher for tacrolimus (2.3 x 10 M)
      than for sirolimus (7.1 x 10 M; P < 0.01). The profile of these drugs on VSMC and
      EC migration was similar to the one found in the proliferation assays. Inhibition
      of VSMC proliferation by both tacrolimus and sirolimus was associated with
      upregulation of the cell-cycle inhibitor p27. Thus, tacrolimus is less potent
      than sirolimus for inhibiting VSMC proliferation or migration. However,
      tacrolimus exerts markedly less antiproliferative effects on EC compared with
      sirolimus. In combination with its potent antiinflammatory effects, tacrolimus
      may represent a promising compound for the use in drug-eluting stents.

PMID- 17204908
TI  - Does the C-type natriuretic peptide have prognostic value in chagas disease and
      other dilated cardiomyopathies?
AB  - Atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP) are
      powerful neurohormonal indicators of left-ventricular function and prognosis in
      heart failure (HF). Chagas disease (CD) caused by the protozoan Trypanosoma cruzi
      remains a major cause of HF in Latin America. We assessed whether the plasma
      concentration of the third natriuretic peptide, C-type natriuretic peptide (CNP),
      also has diagnostic and prognostic properties in patients with CD or other
      dilated cardiomyopathies (DCM). Blood samples were obtained from 66 patients with
      CD, 50 patients with DCM from other causes, and 30 gender- and age-matched
      healthy subjects. Patients were subdivided according to the New York Heart
      Association (NYHA) class. The CNP concentration was determined by
      radioimmunoassay (Immundiagnostik, Bensheim, Germany). The main duration of
      follow-up was 31.4 months (range 13 to 54 months); 19 patients had died and 11
      patients received a heart transplant. CNP concentrations were only significantly
      altered in patients with DCM or CD of the NYHA classes III and IV (P < 0.05). The
      Pearson correlation of echocardiographic data with CNP revealed an association
      only with the left-ventricular end systolic volume (P = 0.03) in patients with
      DCM. Furthermore, CNP did not predict mortality or the necessity for heart
      transplant. Our data are the first to demonstrate the raised levels of the third
      natriuretic peptide CNP in CD and other DCM. Whereas ANP and BNP have a high
      predictive value for mortality in both diseases, CNP is without any predictive
      potency.

PMID- 17204909
TI  - Peroxisome proliferator-activated receptor gamma ligand pioglitazone alters
      neointimal composition in a balloon-denuded and radiated hypercholesterolemic
      rabbit.
AB  - Peroxisome proliferator-activated receptor (PPAR)-gamma activation suppresses
      inflammatory response, monocyte recruitment, and vascular cell proliferation.
      Because inflammation, deregulated growth, and migration of monocytes and vascular
      smooth muscle cells (VSMC) play important roles in the development of neointima,
      we tested the effect of pioglitazone, a high-affinity ligand, for PPAR-gamma on
      neointima formation in the iliac arteries of a balloon-denuded and radiated
      hypercholesterolemic rabbit. Rabbits were fed a 1.0% cholesterol diet for 7 days
      followed by denudation of endothelial layer and continued on a 0.15% cholesterol
      diet. On day 32, animals were divided into 2 groups. One group received a 0.15%
      cholesterol diet (n = 7) and the other group received a 0.15% cholesterol diet
      supplemented with 400 mg of pioglitazone per kilogram. On day 35, the balloon
      denuded area was radiated. Four weeks after radiation, animals were sacrificed
      and arterial segments were processed for morphometry and immunohistochemistry.
      Data analysis showed that the pioglitazone group had smaller neointima (0.85 +/-
      0.36 vs. 1.41 +/- 0.56, P < 0.05), with more cells positive for VSMC (23.07 +/-
      6.16 vs. 18.33 +/- 5.19, P = 0.04), less for monocytes (16.01 +/- 5.33 vs. 21.29
      +/- 4.33, P < 0.05), and fewer cells expressing metalloproteinase (MMP)-1 and MMP
      9 (3.69 +/- 0.47 vs. 4.82 +/- 0.93, P < 0.05 and 3.24 +/- 0.71 vs. 4.29 +/- 0.74,
      P < 0.05, respectively). Pioglitazone reduced neointimal area and modified its
      composition in a balloon-denuded and radiated hypercholesterolemic rabbit model.

PMID- 17204910
TI  - Physiologically tolerable insulin reduces myocardial injury and improves cardiac
      functional recovery in myocardial ischemic/reperfused dogs.
AB  - This study was designed to examine whether physiologically tolerable insulin,
      which maintains lower blood glucose, can protect the myocardium against
      ischemia/reperfusion (I/R) injury in a preclinical large animal model. Adult dogs
      were subjected to 50 minutes of myocardial ischemia (80% reduction in coronary
      blood flow) followed by 4 hours of reperfusion and treated with vehicle, glucose
      insulin-potassium (GIK; glucose, 250 g/L; insulin, 60 U/L; potassium, 80 mmol/L),
      GK, or low-dose insulin (30 U/L) 10 minutes before reperfusion. Treatment with
      GIK exerted significant cardioprotective effects as evidenced by improved cardiac
      function, improved coronary blood flow, reduced infarct size, and myocardial
      apoptosis. In contrast, treatment with GK increased blood glucose level and
      aggravated myocardial I/R injury. It is interesting that treatment with insulin
      alone at the dose that reduced blood glucose to a clinically tolerable level
      exerted significant cardioprotective effects that were comparable to that seen in
      the GIK-treated group. This low-dose insulin had no effect on coronary blood flow
      after reperfusion but markedly reduced coronary reactive hyperemia and switched
      myocardial substrate uptake from fat to carbohydrate. Our results suggest that
      lower glucose supply to the ischemic myocardium at early reperfusion may create a
      "metabolic postconditioning" and thus reduce myocardial ischemia/reperfusion
      injury after prolonged reperfusion.

PMID- 17204911
TI  - Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma
      butyrobetaine contents and cardioprotection in isolated rat heart infarction.
AB  - The inhibition of gamma-butyrobetaine (GBB) hydroxylase, a key enzyme in the
      biosynthesis of carnitine, contributes to lay ground for the cardioprotective
      mechanism of action of mildronate. By inhibiting the biosynthesis of carnitine,
      mildronate is supposed to induce the accumulation of GBB, a substrate of GBB
      hydroxylase. This study describes the changes in content of carnitine and GBB in
      rat plasma and heart tissues during long-term (28 days) treatment of mildronate
      [i.p. (intraperitoneal) 100 mg/kg/daily]. Obtained data show that in concert with
      a decrease in carnitine concentration, the administration of mildronate caused a
      significant increase in GBB concentration. We detected about a 5-fold increase in
      GBB contents in the plasma and brain and a 7-fold increase in the heart. In
      addition, we tested the cardioprotective effect of mildronate in isolated rat
      heart infarction model after 3, 7, and 14 days of administration. We found a
      statistically significant decrease in necrotic area of infarcted rat hearts after
      14 days of treatment with mildronate. The cardioprotective effect of mildronate
      correlated with an increase in GBB contents. In conclusion, our study, for the
      first time, provides experimental evidence that the long-term administration of
      mildronate not only decreases free carnitine concentration, but also causes a
      significant increase in GBB concentration, which correlates with the
      cardioprotection of mildronate.

PMID- 17204912
TI  - Inhibition of TNF-alpha reduces myocardial injury and proinflammatory pathways
      following ischemia-reperfusion in the dog.
AB  - We examined whether tumor necrosis factor-alpha (TNF-alpha) promotes postischemic
      inflammation and myocardial injury via activation of nuclear factor kappa B
      (NFkappaB) in an in vivo canine model. Isoflurane-anesthetized dogs underwent
      closed-chest balloon occlusion of the anterior descending coronary artery for 90
      minutes, followed by reperfusion for 3 hours. Dogs randomly received a soluble
      TNF inhibitor (etanercept, 0.5 mg/kg intravenously) or saline before occlusion.
      Collateral blood flow and risk region size (RISK) were measured with radioactive
      microspheres, infarct size (INF) was measured by triphenyltetrazolium chloride
      staining, inflammation was measured by tissue myeloperoxidase (MPO) activity,
      intercellular adhesion molecular-1 (ICAM-1) messenger ribonucleic acid (mRNA) was
      measured by Northern blotting, and ICAM-1 protein expression was measured by
      Western blotting. NFkappaB activation was measured in nuclear extracts by
      electrophoretic mobility shift assays. INF/RISK was significantly smaller in the
      etanercept group than in the saline control group after adjusting for collateral
      flow (P < 0.009 by analysis of covariance, mean reduction in INF/RISK = 40%, 0.32
      +/- 0.09 versus 0.53 +/- 0.09). MPO activity, ICAM-1 mRNA and protein expression,
      and NFkappaB binding activity were all significantly reduced in the etanercept
      group. Administration of a soluble TNF-alpha inhibitor reduced NFkappaB
      activation, ICAM-1 upregulation, and myocardial injury following ischemia
      reperfusion. TNF-alpha appears to play a significant role in vivo in the genesis
      of postischemic inflammation.

PMID- 17204913
TI  - Putting ocular neuromyotonia in context.

PMID- 17204914
TI  - Ocular neuromyotonia with spastic lid closure.
AB  - Ocular neuromyotonia is characterized by tonic spasms of extraocular muscles
      evoked by eccentric gaze that induces transient strabismus and diplopia. We
      report the case of a 70-year-old woman who initially presented with unilateral
      deficits in fifth and sixth cranial nerve functions attributed to a fifth cranial
      nerve schwannoma. After radiation treatment, she developed neuromyotonia and
      synkinesis of the ipsilateral third cranial nerve. During the attacks of
      neuromyotonia, the left eyelids were often spastically closed, a phenomenon not
      previously reported. The ocular neuromyotonia regressed spontaneously within 3
      years, but components of the synkinesis persisted. Ephaptic transmission in a
      damaged third cranial nerve may be responsible for the neuromyotonia and
      synkinesis. Synkinesis is a more enduring manifestation.

PMID- 17204915
TI  - Primary aberrant regeneration and neuromyotonia of the third cranial nerve.
AB  - A 52-year-old woman presented with episodic diplopia with a duration of 6 months.
      Between the episodes, infraduction of the right eye was mildly impaired with
      retraction of the right upper lid on downgaze. On resuming the primary position
      after prolonged left gaze, she developed a right esotropia and reduced abduction,
      supraduction, and infraduction of the right eye. There was no history of cranial
      radiation or previous diagnosis of a brain lesion. Brain imaging results were
      negative. The interictal infraduction deficit and lid retraction were interpreted
      as signs of a mild right third cranial nerve palsy with primary aberrant
      regeneration. The episodic esotropia and ductional deficits were considered to be
      signs of neuromyotonia. This combination of findings, rarely described before,
      suggests a link between primary aberrant regeneration and neuromyotonia. Abnormal
      and excessive conduction triggered by stimulation of a partially damaged nerve
      probably underlies ocular neuromyotonia.

PMID- 17204916
TI  - Evolution of brain imaging abnormalities in mitochondrial encephalomyopathy with
      lactic acidosis and stroke-like episodes.
AB  - An 18-year-old man developed consecutive homonymous hemianopias that were
      eventually attributed to mitochondrial encephalomyopathy with lactic acidosis and
      stroke-like episodes (MELAS). The diagnosis was initially suspected when brain CT
      scans showed bilateral dystrophic basal ganglia calcifications and MR
      spectroscopy later showed a prominent lactate peak. Diffusion-weighted MRI showed
      progressive evolution of restricted proton diffusion at the margins of the lesion
      from day 3 through 3 weeks. Genetic testing from peripheral blood confirmed an
      A3243G transition in the patient's MTTL1 gene encoding the transfer RNA for
      leucine. The patient's visual function improved, but severe atrophy of gray and
      white matter was visible on MRI.

PMID- 17204917
TI  - The ratio of square wave jerk rates to blink rates distinguishes progressive
      supranuclear palsy from Parkinson disease.
AB  - BACKGROUND: Distinguishing progressive supranuclear palsy (PSP) from Parkinson
      disease (PD) may be difficult, particularly in the early stages, because the
      characteristic vertical supranuclear eye movement abnormalities of PSP may be
      absent or delayed until late in the course of the disease. In this study we
      investigated the usefulness of comparing the square wave jerk rate (SWJR) and
      blink rate (BR) in the differentiation of these two disorders. METHODS: We
      studied 10 patients with PD (PD group) and 5 patients with PSP (PSP group) who
      met published diagnostic criteria. The SWJR and BR were measured from video
      recordings and were used to calculate a ratio (SWJR:BR). RESULTS: The PSP group
      exhibited a significantly higher SWJR, higher SWJR:BR, and lower BR than did the
      PD group. No patient with PSP exhibited a SWJR:BR of < 3; however, one patient
      with PD had a SWJR:BR of 5.3, creating overlap between the two groups.
      CONCLUSIONS: The SWJR:BR is a simple and reasonably useful clinical measure to
      distinguish established PSP from PD. Determining the value of this measure in
      differentiating early PSP from PD requires a prospective study.

PMID- 17204918
TI  - Papilledema in the assessment of ventriculomegaly.
AB  - To determine whether ventriculomegaly is associated with ongoing increased
      intracranial pressure (ICP), physicians often rely on corroborative imaging
      features such as altered periependymal signal, distortion of ventricular shape,
      subarachnoid space flattening, and an increase in ventricular size over time. In
      2 patients with new headache and altered mental status, symptoms and
      ventriculomegaly were dismissed as long-standing and not reflective of current
      ICP elevation. In the first patient, ICP was considered normal because there were
      no corroborative imaging features of elevated ICP. In the second patient, ICP was
      considered normal because ventricular size was stable over a 1-year period. The
      diagnosis of ICP elevation was finally made by ICP monitoring after papilledema
      was recognized. Ventriculoperitoneal shunting rapidly resolved the papilledema
      and markedly improved mentation. Brain imaging may often be an unreliable guide
      to the presence of elevated ICP. In such patients, the finding of papilledema is
      a critical determinant of management.

PMID- 17204919
TI  - Mitochondrial DNA haplogroup distribution in pedigrees of Southeast Asian G11778A
      Leber hereditary optic neuropathy.
AB  - To investigate the association of mitochondrial DNA (mtDNA) haplogroups and Leber
      hereditary optic neuropathy (LHON) in the Southeast Asian population, mtDNA
      haplogroup determination was performed by high-resolution restriction fragment
      length polymorphism in 42 patients with LHON who were carrying the G11778A
      mutation and in control subjects drawn from a Thai urban population unaffected by
      LHON. The patients with LHON were of Thai, Thai-Chinese, and Indian origin. Three
      mtDNA haplogroups, M, B*, and B, were found in LHON patients in a frequency
      similar to that in control subjects. mtDNA haplogroup F was found in none of the
      patients with LHON but was the second most common haplogroup in control subjects.
      The G11778A mutation must have arisen in our population independently from the
      mutation in Caucasians. In contrast to Caucasians, no specific mtDNA haplotype
      was associated with the patients with LHON in the Southeast Asian population. The
      mitochondrial polymorphisms that modify the expression of LHON in Southeast
      Asians could not be identified in this study. The lack of haplogroup F in our
      patients with LHON may indicate the protective effect of this haplogroup in the
      expression of this disorder.

PMID- 17204920
TI  - Leber hereditary optic neuropathy possibly triggered by exposure to tire fire.
AB  - We report three members of one family, a mother and two daughters aged 4 and 7
      years, who developed visual loss from Leber hereditary optic neuropathy within a
      19-month period. All three had been exposed to smoke from two large rubber tire
      fires within the previous 24 months, suggesting the possibility of an epigenetic
      triggering factor.

PMID- 17204921
TI  - Intraocular pressure is low in eyes with giant cell arteritis.
AB  - BACKGROUND: Although ocular ischemia occurs in giant cell arteritis (GCA),
      intraocular pressure (IOP) has not been systematically evaluated as a diagnostic
      sign. METHODS: We conducted a retrospective, case-controlled, observational study
      of IOP in patients with ocular manifestations of GCA (GCA patients), age-matched
      patients diagnosed with nonarteritic ischemic optic neuropathy (NAION patients),
      and age-matched patients with cataract (control patients). Medical records were
      examined for all consecutive patients with the diagnosis of GCA from 1995 to 2004
      (n = 16) and NAION from 2002 to 2004 (n = 16) and for patient candidates for
      cataract extraction (n = 16). The eye intended for cataract extraction was chosen
      as the "affected eye" in the control patients. RESULTS: The mean IOP in the
      affected eye of 16 GCA patients was 11.9 mm Hg, significantly lower than the 15.1
      mm Hg in affected eyes of age-matched NAION patients and 15.8 mm Hg in control
      patients (P = 0.002). At presentation, 5 GCA patients had IOP < 10 mm Hg (mean
      6.8 mm Hg) without other signs of anterior segment ischemia. None of the NAION or
      control patients displayed such low IOPs. CONCLUSIONS: IOP was significantly
      lower in the patients with GCA than in patients with NAION or cataract. Hypotony
      occurred in one third of GCA patients without other signs of anterior ocular
      ischemia. These findings suggest that low IOP may be a distinguishing factor
      between GCA and NAION in patients with ischemic optic neuropathy, but evaluation
      of a larger group of patients is needed for confirmation.

PMID- 17204922
TI  - Pontine tuberculoma presenting with horizontal gaze palsy.
AB  - A 38-year-old immunocompetent man presented with a horizontal supranuclear gaze
      palsy as the only neurologic manifestation of a pontine tuberculoma. Although a
      biopsy of the brain lesion was not performed, it was attributed to tuberculosis
      because of chest x-ray evidence. The patient was given empirical anti-tuberculous
      therapy. After one month, the gaze palsy had fully recovered and repeat MRI
      showed a decrease in the size of the lesion. This is the first reported case of
      supranuclear gaze palsy without diplopia as a manifestation of a tuberculous
      brain stem lesion.

PMID- 17204923
TI  - Chiari type capital I, Ukrainian malformation associated with morning glory disc
      anomaly.
AB  - Morning glory disc anomaly (MGDA) is a congenital malformation of the optic disc
      that has been reported in association with midline craniofacial defects such as
      basal encephalocele, hypertelorism, cleft lip and palate, and agenesis of the
      corpus callosum. We describe a 44 year-old woman with MGDA and Chiari type
      capital I, Ukrainian malformation, an association not previously reported.

PMID- 17204924
TI  - Tilted optic discs visualized by magnetic resonance imaging.
AB  - A young woman with headaches displayed ophthalmoscopic features suggestive of
      papilledema. MRI showed no intracranial abnormalities but demonstrated oblique
      insertion of the optic nerve into the left globe and posterior nasal flattening
      of the left globe, features consistent with congenitally tilted optic discs. This
      is the second report to show that orbital MRI can demonstrate this phenomenon.

PMID- 17204925
TI  - Advances in imaging of the optic disc and retinal nerve fiber layer.
AB  - In the past decade, three technologies for imaging the optic disc and retinal
      nerve fiber layer have become commercially available: 1) confocal scanning laser
      tomography with the Heidelberg retinal tomograph; 2) confocal scanning laser
      polarimetry with the GDx VCC; and 3) optical coherence tomography with the
      Stratus OCT. Each uses different principles of physics. Understanding the merits
      and limitations of each of these technologies requires familiarity with the
      principles of operation of each device. This knowledge should be considered a
      prerequisite for the appropriate clinical utilization of these devices and for
      accurate interpretation of their results.

PMID- 17204926
TI  - Isolated sixth cranial nerve palsy in preeclampsia.

PMID- 17204927
TI  - Recurrent isolated horner syndrome.

PMID- 17204928
TI  - Topical apraclonidine testing of pupillary sympathetic denervation in diabetic
      patients.

PMID- 17204931
TI  - The evolution of mathematical modeling of glioma proliferation and invasion.
AB  - Gliomas are well known for their potential for aggressive proliferation as well
      as their diffuse invasion of the normal-appearing parenchyma peripheral to the
      bulk lesion. This review presents a history of the use of mathematical modeling
      in the study of the proliferative-invasive growth of gliomas, illustrating the
      progress made in understanding the in vivo dynamics of invasion and proliferation
      of tumor cells. Mathematical modeling is based on a sequence of observation,
      speculation, development of hypotheses to be tested, and comparisons between
      theory and reality. These mathematical investigations, iteratively compared with
      experimental and clinical work, demonstrate the essential relationship between
      experimental and theoretical approaches. Together, these efforts have extended
      our knowledge and insight into in vivo brain tumor growth dynamics that should
      enhance current diagnoses and treatments.

PMID- 17204932
TI  - Mitochondrial alterations in the spinal cord of patients with sporadic
      amyotrophic lateral sclerosis.
AB  - Little information is available about morphologic changes of mitochondria in
      sporadic amyotrophic lateral sclerosis (ALS). We examined the anterior horns of
      the lumbar spinal cord in 14 patients with sporadic ALS and 15 age-matched
      controls by electron microscopy to illuminate the subject. In the controls, one
      patient showed occasional swollen mitochondria with markedly increased cristae
      and marked accumulation of mitochondria in the somata of anterior horn neurons.
      Another patient had periodic, stubby protrusions on the outer membrane. Among the
      patients with ALS, 7 showed filamentous structures in the inner compartment of
      the mitochondria mainly of the somata and only occasionally of the axons. The
      structures were composed of a stack of multilayered cristae consisting of linear
      structures on a longitudinal section. Other abnormal structures were periodic
      transverse processes like rungs of a ladder predominantly in somata and only
      occasionally in the axons, marked accumulation of mitochondria in the somata,
      dendrites or proximal axons (axon hillock and initial segment), stubby
      protrusions on the outer membrane, and swollen mitochondria with markedly
      increased cristae in the somata. The findings in this study may reflect the
      metabolic disturbance of mitochondria, probably associated with the
      pathomechanism of degenerative processes of anterior horn neurons in sporadic
      ALS.

PMID- 17204933
TI  - The DeltaK280 mutation in MAP tau favors exon 10 skipping in vivo.
AB  - Tau mutations in frontotemporal dementia and parkinsonism linked to chromosome 17
      (FTDP-17) are associated with changes in alternative splicing of exon 10. The
      DeltaK280 mutation in exon 10 is exceptional because in vitro observations
      suggest a dramatic effect on microtubule binding, enhanced self-aggregation, as
      well as a decrease of the 4R/3R ratio by the ablation of an exon splicing
      enhancer element. Using immunohistochemistry, Western blotting, and electron
      microscopy on brain material with the DeltaK280 mutation, we investigated which
      of these effects is most dominant in vivo. The brain showed abundant Pick bodies
      in several brain regions, which stained positive with 3-repeat-specific but not
      with 4-repeat-specific tau antibodies. Western blots of sarkosyl-insoluble tau
      showed exclusively three repeat (3R0N and 3R1N) tau in most regions, although
      some 4R1N could be detected in the frontal cortex. In addition, the sarkosyl
      soluble tau fraction showed a significantly higher amount of 3-repeat tau.
      Because quantitative analysis of 4R and 3R mRNA transcripts showed a 4R/3R ratio
      of only 0.3, association between increased transcription and protein expression
      was observed. These observations confirm the postulated hypothesis that the
      DeltaK280 mutation abolishes a splice enhancer element, which overrules the
      decreased microtubule binding and enhanced self-aggregation.

PMID- 17204934
TI  - Pathogenesis of simian immunodeficiency virus-induced alterations in macaque
      trigeminal ganglia.
AB  - Peripheral neuropathy is the most frequent neurologic complication associated
      with human immunodeficiency virus (HIV) infection, yet its pathogenesis remains
      poorly understood. To study the mechanisms causing HIV-induced peripheral nervous
      system disease, we examined trigeminal ganglia obtained from simian
      immunodeficiency virus (SIV)-inoculated macaques. SIV-infected macaques developed
      multifocal trigeminal ganglionitis of varying severity characterized by
      multifocal mononuclear infiltrates, neuronophagia, and neuronal loss resembling
      reports of HIV-associated changes present in dorsal root ganglia. Neuronal
      density, measured by calculating the fractional area of trigeminal ganglia
      occupied by neurons, was significantly lower in SIV-infected macaques versus
      uninfected macaques (p = 0.001). To characterize the inflammatory cell population
      and measure productive viral infection in ganglia, trigeminal ganglia from SIV
      infected macaques were immunostained for macrophage or cytotoxic lymphocyte
      markers and for SIV gp41. The extent of macrophage infiltration in trigeminal
      ganglia was inversely correlated with neuronal loss (p = 0.001), whereas
      cytotoxic lymphocyte infiltration was not associated with neuronal loss. These
      studies demonstrate that alterations in the somatosensory ganglia of SIV-infected
      macaques closely parallel those observed in HIV-infected individuals and show
      that study of SIV-infected macaques may help elucidate the pathophysiology of HIV
      induced peripheral neuropathy.

PMID- 17204935
TI  - Brain protein preservation largely depends on the postmortem storage temperature:
      implications for study of proteins in human neurologic diseases and management of
      brain banks: a BrainNet Europe Study.
AB  - The present study was designed to reveal protein modifications in control cases
      related with postmortem delay and temperature of storage in 3 paradigms in which
      the same postmortem tissue sample (frontal cortex) was frozen a short time after
      death or stored at 1 degrees C, 4 degrees C, or room temperature and then frozen
      at -80 degrees C at different intervals. No evidence of protein degradation as
      revealed with monodimensional gel electrophoresis and Western blotting was
      observed in samples artificially stored at 1 degrees C and then frozen at
      different intervals up to 50 hours after death. However, the levels of several
      proteins were modified in samples stored at 4 degrees C and this effect was more
      marked in samples stored at room temperature. Two-dimensional gel electrophoresis
      and mass spectrometry further corroborated these observations and permitted the
      identification of other proteins vulnerable or resistant to postmortem delay.
      Finally, gel electrophoresis and Western blotting of sarkosyl-insoluble fractions
      in Alzheimer disease showed reduced intensity of phospho-tau-specific bands with
      postmortem delay with the effects being more dramatic when the brain samples were
      stored at room temperature for long periods. These results emphasize the
      necessity of reducing the body temperature after death to minimize protein
      degradation.

PMID- 17204936
TI  - Downregulation of transforming growth factor-beta2 facilitates inflammation in
      the central nervous system by reciprocal astrocyte/microglia interactions.
AB  - The central nervous system is an immune privileged organ in which inflammatory
      reactions are normally downregulated by mechanisms that are not completely
      understood. Transforming growth factor (TGF)-beta2 is constitutively expressed in
      the adult central nervous system and little is known about its regulation and
      modulatory role during neuroinflammation. In this study, we show that TGFbeta2
      mRNA and protein are downregulated in the acute phase of chronic relapsing
      experimental autoimmune encephalomyelitis, whereas the homologous cytokine
      TGFbeta1 is upregulated. To further characterize regulatory mechanisms, we
      resorted to an in vitro glial cell culture system. The proinflammatory cytokines
      IFNgamma and TNFalpha suppressed TGFbeta2 secretion by astrocytes, the major
      intracerebral producers of TGFbeta2. On the cellular level, activated microglia
      inhibited TGFbeta2 secretion but induced TGFbeta1 through soluble factors. On the
      other hand, TGFbeta2 influenced antigen-presenting cell functions of microglia by
      downregulating major histocompatibility complex class II expression and
      costimulatory/adhesion molecules, and thereby inhibited myelin basic protein
      specific T cell proliferation. These data suggest that TGFbeta2 plays a central
      role in maintenance of the immune privilege of the central nervous system.
      Downregulation of astrocytic TGFbeta2 by T cell- and microglia-secreted cytokines
      appears to be a critical step in providing the grounds for acute and chronic
      neuroinflammation.

PMID- 17204937
TI  - Abnormal distribution of calcium-handling proteins: a novel distinctive marker in
      core myopathies.
AB  - Central core disease (CCD) and multi-minicore disease (MmD) are muscle disorders
      characterized by foci of mitochondria depletion and sarcomere disorganization
      ("cores") in muscle fibers. Although core myopathies are the most frequent
      congenital myopathies, their pathogenesis remains elusive and specific diagnostic
      markers are lacking. Core myopathies are mostly caused by mutations in 2
      sarcoplasmic reticulum proteins: the massive Ca-release channel RyR1 or the
      selenoprotein N (SelN) of unknown function. To search for distinctive markers and
      to obtain further pathophysiological insight, we identified the molecular defects
      in 12 core myopathy patients and analyzed the immunolocalization of 6 proteins of
      the Ca-release complex in their muscle biopsies. In 7 cases with RYR1 mutations
      (6 CCD, one MmD), RyR1 was depleted from the cores; in contrast, the other
      proteins of the sarcoplasmic reticulum (calsequestrin, SERCA1/2, and triadin) and
      the T-tubule (dihydropyridine receptor-alpha1subunit) accumulated within or
      around the lesions, suggesting an original modification of the Ca-release complex
      protein arrangement. Conversely, all Ca-related proteins were distributed
      normally in 5 MmD cases with SelN mutations. Our results provide an appropriate
      tool to orientate the differential and molecular diagnosis of core myopathies and
      suggest that different pathophysiological mechanisms lead to core formation in
      SelN- and in RyR1-related core myopathies.

PMID- 17204938
TI  - p53 transcription-dependent and -independent regulation of cerebellar neural
      precursor cell apoptosis.
AB  - Regulation of cerebellar neural precursor cell (NPC) death is important for both
      normal brain development and prevention of brain tumor formation. The tumor
      suppressor p53 is an important regulator of NPC apoptosis, but the precise
      mechanism of p53-regulated cerebellar NPC death remains largely unknown. Here, by
      using primary cerebellar NPCs and a mouse cerebellar NPC line, we compared the
      molecular regulation of cerebellar NPC death produced by staurosporine (STS), a
      broad-spectrum kinase inhibitor, with that caused by genotoxic agents. We found
      that both STS- and genotoxin-induced cerebellar NPC death were markedly inhibited
      by p53 or Bax deficiency. Genotoxin-induced cerebellar NPC death required new
      protein synthesis and PUMA, a p53 transcriptionally regulated BH3-only molecule.
      In contrast, STS caused cerebellar NPC death without requiring new protein
      synthesis or PUMA expression. In addition, genotoxic agents increased nuclear p53
      immunoreactivity, whereas STS produced rapid cytoplasmic p53 accumulation.
      Interestingly, STS-induced death of cerebellar granule neurons was p53
      independent, indicating a differentiation-dependent feature of neuronal apoptotic
      regulation. These results suggest that STS-induced cerebellar NPC death requires
      a direct effect of p53 on cytoplasmic apoptotic mediators, whereas genotoxin
      induced death requires p53-dependent gene transcription of PUMA. Thus, p53 has
      multiple death promoting mechanisms in cerebellar NPCs.

PMID- 17204939
TI  - Expression of Nrf2 in neurodegenerative diseases.
AB  - In response to oxidative stress, the nuclear factor E2-related factor 2 (Nrf2)
      transcription factor translocates from the cytoplasm into the nucleus and
      transactivates expression of genes with antioxidant activity. Despite this
      cellular mechanism, oxidative damage is abundant in Alzheimer and Parkinson
      disease (AD and PD). To investigate mechanisms by which Nrf2 activity may be
      aberrant or insufficient in neurodegenerative conditions, we assessed Nrf2
      localization in affected brain regions of AD, Lewy body variant of AD (LBVAD),
      and PD. By immunohistochemistry, Nrf2 is expressed in both the nucleus and the
      cytoplasm of neurons in normal hippocampi with predominant expression in the
      nucleus. In AD and LBVAD, Nrf2 was predominantly cytoplasmic in hippocampal
      neurons and was not a major component of beta amyloid plaques or neurofibrillary
      tangles. By immunoblotting, we observed a significant decrease in nuclear Nrf2
      levels in AD cases. In contrast, Nrf2 was strongly nuclear in PD nigral neurons
      but cytoplasmic in substantia nigra of normal, AD, and LBVAD cases. These
      findings suggest that Nrf2-mediated transcription is not induced in neurons in AD
      despite the presence of oxidative stress. In PD, nuclear localization of Nrf2 is
      strongly induced, but this response may be insufficient to protect neurons from
      degeneration.

PMID- 17204940
TI  - Upregulation of hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha in
      leptomeningeal vascular malformations of Sturge-Weber syndrome.
AB  - Cutaneous and leptomeningeal vascular malformations are hallmarks of the Sturge
      Weber Syndrome (SWS), resulting in chronic ischemic tissue damage. The mechanisms
      underlying the pathobiology of these progressive lesions are unknown. Aberrant
      expression of angiogenic factors has been implicated in the genesis and
      maintenance of vascular malformations. To assess the role of angiogenesis in SWS
      vascular lesions we determined the expression of key angiogenic factors by
      immunohistochemistry and in situ hybridization in 8 SWS patients (age: 8 months
      to 18 years). We observed increased expression of vascular endothelial growth
      factor (VEGF), its cognate receptors VEGFR-1, VEGFR-2, and neuropilin (NP)-1 as
      well as Tie2 in leptomeningeal SWS blood vessels. Intriguingly, these factors are
      known to be transcriptionally induced by hypoxia-inducible factor (HIF). The HIF
      system has emerged as the key regulatory system of responses to hypoxia.
      Immunohistochemical analysis demonstrated markedly elevated nuclear HIF-1alpha
      and HIF-2alpha protein levels in SWS vessels. Concomitantly, SWS vessels revealed
      signs of enhanced endothelial cell (EC) turnover as evidenced by increased EC
      proliferation and apoptosis. Thus, in terms of angiogenesis, vascular
      malformations in SWS are not static lesions but constitute dynamic structures.
      Our observation of a dysregulated HIF-alpha expression in SWS vessels are in
      agreement with recent findings that EC-specific HIF activation provides a setting
      which supports and sustains angiogenesis and could be of potential use for
      developing therapeutic strategies to treat these currently incurable lesions.

PMID- 17204942
TI  - Presentation of the 2006 Shwachman Award to Judith M. Sondheimer, MD.

PMID- 17204943
TI  - Presentation of the 2006 NASPGHAN Distinguished Service Award to Harvey L. Sharp,
      MD.

PMID- 17204944
TI  - Presentation of the 2006 Murray Davidson Award to George D. Ferry, MD.

PMID- 17204945
TI  - Functional nonretentive fecal incontinence in children.
AB  - Fecal incontinence, the loss of feces in the underwear after age 4 years, is a
      frustrating phenomenon for children and their parents. It is difficult to treat,
      presenting as a single symptom without any organic cause or signs of
      constipation. This review addresses the definition of functional nonretentive
      fecal incontinence and provides an overview of its epidemiology, pathophysiology,
      clinical features, diagnostic work-up and prognosis.

PMID- 17204946
TI  - Hepatitis B virus: something old, something new.

PMID- 17204947
TI  - Autoimmune hepatitis: are we using the right therapy?

PMID- 17204948
TI  - Activated mucosal mast cells differentiate eosinophilic (allergic) esophagitis
      from gastroesophageal reflux disease.
AB  - OBJECTIVES: To evaluate the utility of activated mucosal mast cells (MC) in the
      differential diagnosis of eosinophilic esophagitis (EE) and gastroesophageal
      reflux disease (GERD). METHODS: Intraepithelial eosinophils and MC were
      quantified in esophageal biopsies from 25 children with EE, 22 children with GERD
      and 22 controls. MCs were identified by immunohistochemistry for MC tryptase,
      whereas MC activation status was evaluated by immunohistochemistry for
      immunoglobulin E (IgE) and by electron microscopy. RESULTS: Esophageal biopsies
      from patients with EE showed higher intraepithelial eosinophil counts (55 +/-
      27.5 vs 6.9 +/- 9.7, P < 0.0001) and MC counts (26.3 +/- 12.7 vs 7.8 +/- 8.9, P <
      0.0001) than those from patients with GERD. Almost all EE biopsies (24 of 25
      patients; 96%) contained IgE-bearing cells compared with 9 of 22 (41%) GERD
      biopsies (P < 0.001). GERD biopsies with intraepithelial eosinophil counts
      >7/high-power field (suggesting an allergic component) contained IgE-bearing
      cells in 6 of 7 (86%) cases compared to 3 of 15 (20%) cases with eosinophil
      counts <7/h.p.f (P < 0.01). No intraepithelial eosinophils, MC or IgE-positive
      cells were present in controls. Electron microscopy confirmed the presence of
      intraepithelial MC and changes in cytoplasmic granules indicative of MC and
      eosinophil activation. CONCLUSIONS: Intraepithelial MC counts and IgE-bearing
      cells may help to differentiate EE and GERD and to define a subset of GERD
      patients in which an allergic component is present. The findings support a role
      for a MC-mediated hypersensitivity reaction in the pathogenesis of EE.

PMID- 17204949
TI  - Morphometric histology for infant gastroesophageal reflux disease: evaluation of
      reliability in 497 esophageal biopsies.
AB  - OBJECTIVES: We sought to determine the reliability of morphometric measurements
      on infant esophageal biopsies using a light microscope with eyepiece micrometer.
      METHODS: We measured epithelial thickness, basal layer thickness (B), papillary
      height (P) and epithelial lymphocyte and eosinophil numbers on approximately 500
      existing esophageal suction biopsies from infants previously evaluated for reflux
      esophagitis. We tested these measurements for interobserver, test-retest and
      internal consistency reliability. RESULTS: Infants ages 0.25 to 23.75 (median,
      6.25) months provided 497 biopsies. Both investigators scoring the biopsies
      independently judged 93% of them scorable. Of the biopsies scored by both, the 2
      readings were within 0.15 of each other for P in 97% and for B in 81%. In
      addition to these correlative measures of consistency, categoric measures
      demonstrated that 373 (89%) of the 420 scorable biopsies with visible papillae
      produced agreement as to P being abnormal (317, 85%) or normal (56, 15%).
      Similarly, 360 (78%) of the 463 scorable biopsies produced agreement as to B
      being abnormal (339, 94%) or normal (21, 6%). P values were 0.17 to 0.94 (median,
      0.67), and B values were 0.13 to 0.91 (median, 0.34). Lymphocytes numbered 0 to
      40 (median 5) per high-power field. Only 12% had any eosinophils; none of those
      with completely normal morphometrics had any eosinophils; and only 2% had >5
      eosinophils per high-power field. CONCLUSIONS: Simple quantitative esophageal
      histological morphometric parameters are reliably measurable on suction biopsies
      from infants using a light microscope fitted with an ocular micrometer, even by
      nonpathologists.

PMID- 17204950
TI  - Pharmacokinetics and pharmacodynamics of lansoprazole in children 13 to 24 months
      old with gastroesophageal reflux disease.
AB  - OBJECTIVES: To evaluate the pharmacokinetics and pharmacodynamics of lansoprazole
      in children between 13 and 24 months of age with gastroesophageal reflux disease
      (GERD). METHODS: From the population of 66 children with symptomatic GERD,
      erosive esophagitis (> or = grade 2) or esophageal pH < 4 for > 4.2% of the 24-h
      period who participated in a phase I/II, open-label, multicenter (11 sites) US
      study, a subanalysis of 8 toddlers between 13 and 24 months of age was performed.
      All children were treated, based on body weight, with lansoprazole 15 mg once
      daily for 8 to 12 weeks. If a child were still symptomatic after 2 weeks of
      treatment, then the dose of lansoprazole could be increased to twice daily at the
      discretion of the investigator. Pharmacokinetic parameters were assessed at day
      5. Twenty-four-hour median intragastric pH and the percentage of time
      intragastric pH > 3 or > 4 were assessed at baseline and at day 5 of treatment.
      Symptom response was assessed by investigator interview and daily diary. Safety
      was monitored by physical examinations including vital signs, adverse event
      assessments and laboratory evaluations. RESULTS: Pharmacokinetic analysis of 5
      children found a mean time to reach maximum concentration of 1.4 h, maximal
      plasma concentrations of 894 ng/mL, area under the concentration time curve of
      1906 ng * h/mL and a half-life of 0.66 h. Significant (P < or = 0.027) increases
      from baseline to day 5 were observed in mean 24-h intragastric pH (2.76-3.52) and
      the percentages of time pH were > 3 (29.46%-55.36%) and pH was > 4 (16.96%
      40.77%). Six of the 8 children had improvement in their overall GERD symptom
      severity on the basis of investigator assessment, and a reduction was seen in the
      percentage of days with moderate, severe or very severe GERD symptoms compared
      with baseline. The dosage of lansoprazole was increased in 3 of the 8 children.
      Median fasting serum gastrin level increased from 65.0 pg/mL at baseline to 136.5
      pg/mL at the final visit. Treatment-related events were mild constipation (1
      subject) and mild diarrhea (1 subject). CONCLUSIONS: Although larger studies are
      needed to confirm these results, lansoprazole displays pharmacokinetic and
      pharmacodynamic parameters in children between 13 and 24 months of age that are
      similar to those results observed in older children as well as adults.

PMID- 17204951
TI  - Effect of omeprazole on acid gastroesophageal reflux and gastric acidity in
      preterm infants with pathological acid reflux.
AB  - INTRODUCTION: Proton pump inhibitor (PPI) therapy is increasingly being used to
      treat premature infants with gastroesophageal reflux disease (GERD); however, the
      efficacy of PPI on acid production in this population has yet to be assessed in
      this patient group. The aim of this study was to determine the effect of 0.7
      mg/kg/d omeprazole on gastric acidity and acid gastroesophageal reflux in preterm
      infants with reflux symptoms and pathological acid reflux on 24-h pH probe.
      METHODS: A randomized, double blind, placebo-controlled, crossover design trial
      of omeprazole therapy was performed in 10 preterm infants (34-40 weeks
      postmenstrual age). Infants were given omeprazole for 7 d and then placebo for 7
      d in randomized order. Twenty-four-hour esophageal and gastric pH monitoring was
      performed on days 7 and 14 of the trial. RESULTS: Compared to placebo, omeprazole
      therapy significantly reduced gastric acidity (%time pH <4, 54% vs 14%, P <
      0.0005), esophageal acid exposure (%time pH <4, 19% vs 5%, P < 0.01) and number
      of acid GER episodes (119 vs 60 episodes, P < 0.05). CONCLUSIONS: Omeprazole is
      effective in reducing esophageal acid exposure in premature infants with
      pathological acid reflux on 24-h pH probe; however, the far more complex issues
      of safety and efficacy have yet to be addressed.

PMID- 17204952
TI  - Wireless video capsule in pediatric patients with functional abdominal pain.
AB  - OBJECTIVES: Upper endoscopy (esophagogastroduodenoscopy [EGD]) has a limited
      role, if any, in the evaluation of functional abdominal pain (FAP). Nevertheless,
      children with intractable FAP are occasionally referred to EGD to rule out
      intestinal pathology. We evaluated the role of wireless video capsule endoscopy
      (VCE) in children referred for EGD with a diagnosis of FAP. PATIENTS AND METHODS:
      Ten children older than 10 years of age were prospectively enrolled. Children
      were first studied with the PillCam SB (VCE; Given Imaging, Yokneam, Israel)
      followed by standard EGD within 2 weeks. After the completion of the study, a
      questionnaire of tolerance and content regarding the 2 procedures was completed
      by the patients. RESULTS: Physical examinations and laboratory tests were within
      normal limits in all of the patients. Patients swallowed the endoscopic capsules
      without difficulty. There were no complications. VCE identified gastritis in 4
      patients (confirmed by biopsies), whereas EGD detected erosive gastritis in only
      1 of the 4 children. EGD detected no duodenal abnormalities. VCE detected Crohn
      disease in the small intestine and cecum in 1 patient. VCE was ranked by 8
      patients as convenient and as a preferable procedure compared with EGD.
      CONCLUSION: The results of this small cohort suggest that in children with FAP,
      VCE is more sensitive than EGD for detection of macroscopic gastric and small
      bowel pathologies.

PMID- 17204953
TI  - Diagnostic utility of the water load test in children with chronic abdominal
      pain.
AB  - OBJECTIVES: To compare water load test consumption patterns between children with
      functional gastrointestinal disorders and healthy control children. METHODS:
      Seventy-one children with recurrent abdominal pain completed the Behavioral
      Assessment Scale for Children-Self-Report Form and the Questionnaire on Pediatric
      Gastrointestinal Symptoms during their first visit to a pediatric
      gastroenterology clinic. Parent- and child-report functional gastrointestinal
      diagnoses were based on the Questionnaire on Pediatric Gastrointestinal Symptoms
      scoring criteria, whereas the clinician's diagnosis was based on clinical
      impression from history and physical examination completed at this visit. Twenty
      six healthy children also participated as controls. Statistical comparisons
      involved Student t tests, whereas receiver operating characteristic curves
      estimated sensitivity/specificity of the water load test and linear regression
      determined the amount of variance accounted for in water volume consumption.
      RESULTS: Children with recurrent abdominal pain, particularly those with a
      diagnosis of functional dyspepsia, consumed less water than healthy children on
      the water load test. The water load test demonstrated good specificity, but poor
      sensitivity, in identifying patients with functional dyspepsia. Clinician
      evaluation provided the greatest differentiation between functional
      gastrointestinal disorders on the water load test. CONCLUSIONS: The water load
      test seems to be a poor diagnostic test for functional dyspepsia because of poor
      sensitivity. However, future research should examine whether the water load test
      is identifying a subset of children with functional dyspepsia experiencing a
      specific mechanosensory dysfunction and whether the water load test can predict
      clinical response to specific therapeutic interventions.

PMID- 17204954
TI  - Multiple somatic symptoms linked to positive screen for depression in pediatric
      patients with chronic abdominal pain.
AB  - OBJECTIVES: Abdominal pain is a frequent childhood complaint, comprising 2% to 4%
      of all reasons for pediatric office visits. Patients referred for evaluation of
      chronic abdominal pain (CAP) frequently present with comorbid nonspecific somatic
      symptoms that may complicate the medical evaluation and lead to unnecessary
      diagnostic tests and procedures. We tested the hypothesis that multiple
      nongastrointestinal (GI) symptoms in children presenting with CAP is a marker for
      clinically significant levels of depressive symptoms. METHODS: Participants were
      400 consecutive new patients (ages 8-17 years; 63% female) referred to the
      pediatric gastroenterology clinic for evaluation of abdominal pain of > 3 months'
      duration. Patients reported how frequently they experienced 7 non-GI symptoms.
      Patients were screened for depression with the Children's Depression Inventory.
      RESULTS: On the basis of their Children's Depression Inventory scores, 58 (15%)
      patients had a positive screen for clinically significant depressive symptoms.
      Patients with a positive versus negative depression screen did not differ by sex,
      pain duration or laboratory evidence of organic disease. Patient report of > or =
      3 non-GI symptoms maximized sensitivity (71%) and specificity (75%) in prediction
      of depression screening results. With each addition of a non-GI symptom, the odds
      of a positive screen for depression doubled. CONCLUSIONS: For patients with and
      without organic disease findings associated with CAP, the presence of > or = 3
      non-GI symptoms should signal the practitioner to evaluate for depression and may
      be used as an indicator of the likelihood of depression in the absence of
      specific inquiry into emotional symptoms.

PMID- 17204955
TI  - Anxiety and pain symptoms in children with inflammatory bowel disease and
      functional gastrointestinal disorders undergoing colonoscopy.
AB  - OBJECTIVE: To compare pain and anxiety scores between children with inflammatory
      bowel disease (IBD) and those with functional gastrointestinal disorders (FGID)
      undergoing colonoscopy and to examine the role of anxiety and procedure length in
      predicting reports of pain. MATERIALS AND METHODS: Children ages 10 to 18 years
      undergoing colonoscopy (general anesthesia) for the first time completed pain and
      anxiety questionnaires immediately before the procedure and a pain questionnaire
      48 hours after colonoscopy. The diagnosis was determined by chart review and
      physician interview. RESULTS: Children with FGID had a longer duration of pain
      than those with IBD. Children with FGID endorsed a greater total number of the
      pain descriptors. The FGID group reported higher usual pain severity and greater
      postprocedural pain. No differences in anxiety were reported. However, higher
      levels of anxiety were associated with higher pain scores at the time of
      colonoscopy in children with IBD. It required significantly more time to perform
      colonoscopy in the IBD group than in the FGID group. Longer procedure duration
      was positively correlated with pain in children with FGID but not in children
      with IBD. CONCLUSIONS: Children with FGID report more usual pain symptoms and may
      describe more pain after a colonoscopy when compared with children with IBD.
      Anxiety appears to play a role in pain severity after colonoscopy in children
      presenting with IBD, but not in children with FGID.

PMID- 17204956
TI  - Comparison of the 13C-urea blood test to histology and rapid urease testing in
      the diagnosis of Helicobacter pylori infection in children.
AB  - OBJECTIVE: Helicobacter pylori infection is commonly investigated in children
      with abdominal pain. The definitive means of diagnosing infection, histology,
      requires endoscopy and sedation, making it invasive and expensive. Our objective
      was to compare histology against a less invasive and safer method, the 13C-urea
      blood test. PATIENTS AND METHODS: Forty children with abdominal pain undergoing
      upper endoscopy were randomized into either of 2 dosages of 13C-urea. Several
      biopsies were taken for histology and rapid urease testing. After endoscopy, each
      child ingested a randomly assigned dosage of either 75 mg or 125 mg 13C-urea, and
      blood was withdrawn 30 min later. RESULTS: Irrespective of the dosage of 13C
      urea, the 13C-urea blood test performed with high accuracy (89%) when compared
      against either histology or rapid urease testing. The sensitivity and specificity
      of the blood test was 83% and 91%, respectively. When the smaller dosage of 13C
      urea was used, the accuracy of the blood test was 100% compared with histology.
      There were no adverse events related to using either dosage of 13C-urea.
      CONCLUSIONS: The 13C-urea blood test may be comparable with histology in
      diagnosing H. pylori infection in children, and the smaller dosage of 13C-urea
      does not adversely affect blood test performance. The 13C-urea blood test is well
      tolerated in children.

PMID- 17204957
TI  - Extraction of the plasticizers diethylhexylphthalate and polyadipate from
      polyvinylchloride nasogastric tubes through gastric juice and feeding solution.
AB  - OBJECTIVES: Except for polyadipate, which is used as an alternative in
      polyvinylchloride (PVC) feeding tubes, diethylhexylphthalate (DEHP) is the
      plasticizer used almost exclusively in PVC medical products. A clear response to
      the chronic intake of DEHP has been shown in several organ systems from different
      species. In the present study, we compared the extraction of DEHP and polyadipate
      from PVC gastric tubes. METHODS: An in vivo setting was simulated. We used 5 cm
      of PVC nasogastric tubes containing DEHP or polyadipate, which were incubated
      with gastric juice for 1 week and a feeding solution for 4 weeks. The leakage of
      these plasticizers was measured daily in the gastric juice group and weekly in
      the feeding solution group. The amount of plasticizer extracted was compared
      between groups and days. RESULTS: In the feeding solution group, the extraction
      of DEHP ranged from 200 to 542 microg after 1 week and from 660 to 1700 microg
      after 4 weeks. The extraction of polyadipate was 10 times lower than that of
      DEHP. In the gastric juice group, extracted DEHP ranged from 635 to 1043 microg,
      whereas the extraction of polyadipate was 100 times lower. CONCLUSIONS: Within 1
      week, the extraction of DEHP from a 5-cm PVC tube reaches up to 1 mg.
      Extrapolated, this represents an in vivo load of up to 4 mg. The load accumulated
      by a newborn in an intensive care unit can therefore easily reach several
      milligrams of DEHP per day. Polyadipate nasogastric tubes may therefore be an
      alternative and help to reduce the daily load of DEHP.

PMID- 17204958
TI  - Arachidonic acid content in adipose tissue is associated with insulin resistance
      in healthy children.
AB  - BACKGROUND: The fatty acid composition of membrane structural lipids, which is
      partly dependent on dietary intake, is associated with insulin action. AIM: To
      examine the association between fatty acid composition of adipose tissue and
      skeletal muscle phospholipids with insulin resistance markers in a healthy
      pediatric population. METHODS: Using a cross-sectional design, we studied 83
      healthy children divided into 3 groups, ages 2 to 5, 6 to 10 and more than 10
      years. MEASUREMENTS: Fatty acid composition of adipose tissue triacylglycerols
      and skeletal muscle phospholipids, plasma lipid profile and fasting plasma levels
      of glucose and insulin were measured. RESULTS: There was a linear increase of
      insulinemia, glycemia and homeostasis adipose tissue model assessment (HOMA)
      index throughout the pediatric age range. Linoleic acid proportion in skeletal
      muscle and arachidonic acid proportion in adipose tissue also increased
      significantly with age. An age-independent positive correlation between
      insulinemia or HOMA index and arachidonic acid content in adipose tissue
      triacylglycerols (r = 0.47, P < 0.001) was found. An age-dependent negative
      correlation was present between insulinemia or HOMA index and oleic acid content
      in skeletal muscle phospholipids (r = -0.30, P = 0.03 and r = -0.28, P < 0.04,
      respectively). Trans fatty acids content did not correlate with any marker of
      insulin resistance. CONCLUSION: Healthy children present a prepubertal increase
      of insulin resistance, which is significantly correlated with arachidonic acid
      content in adipose tissue.

PMID- 17204959
TI  - Natural history of chronic hepatitis B virus infection in children of different
      ethnic origins: a cohort study with up to 12 years' follow-up in northern Greece.
AB  - AIM: To investigate the mode of transmission and the natural history of chronic
      hepatitis B virus (HBV) infection in children of different ethnicities in Greece.
      This study was part of the Interreg I-II EC project. PATIENTS AND METHODS: One
      hundred seventy-three hepatitis B surface antigen (HBsAg)(+) carriers, median age
      6.9 (5-12) y, were prospectively followed-up for a mean period of 5.3 (1-12) y
      for serological markers of HBV infection, serum alanine aminotransferase (ALT),
      HBV-DNA, alpha-fetoprotein levels and ultrasonography. RESULTS: Vertical
      transmission predominates (61.8%) in Moslem children and horizontal (44%) in
      those born in Russia. At entry, 73 of 173 (42%) HBsAg(+) genotype D children were
      hepatitis B e antigen (HBeAg)(+), ranging from 27% to 67% among ethnic groups; 55
      of 173 (32%) had ALT > 2 x upper normal limit (UNL), ranging from 21% to 39%. Of
      100 anti-HBe(+) children, 85 (85%) were inactive carriers. During the follow-up
      period, seroconversion to anti-HBe was observed in 40 of 73 (55%) children with
      an annual rate of 11%; 35 of 40 (87.5%) had biochemical remission, and 28 of 35
      (80%) lost HBV-DNA. In the anti-HBe(+) group, 27 of 100 (27%) lost HBV-DNA and 9
      of 100 (9%) lost HBsAg. The annual seroconversion rate for HBeAg was
      significantly lower: in children with vertical transmission compared with
      horizontal (7.7% vs 14.8%, respectively, P < 0.001) and in Muslim children
      compared with both Christian children and those born in Russia (8.6% vs 12%,
      respectively, P < 0.001). No differences were found among the ethnic groups after
      adjusting for the mode of infection. Two of 173 children had progression of liver
      disease. CONCLUSIONS: The differences in HBeAg(+) status and seroconversion rate
      among the ethnic groups are related to the time/mode of HBV infection. The
      majority of children who developed anti-HBe immunity had biochemical remission,
      and a substantial number of the inactive carriers lost viremia during the
      observation period of up to 12 y.

PMID- 17204960
TI  - Long-term therapeutic efficacy of lamivudine compared with interferon-alpha in
      children with chronic hepatitis B: the younger the better.
AB  - OBJECTIVES: To assess and compare the long-term therapeutic response to
      lamivudine compared with interferon-alpha (IFN-alpha) in children with chronic
      hepatitis B. METHODS: A total of 40 children (27 male; age, 1.3-18 y, mean, 7.7
      y) with chronic hepatitis B who received lamivudine for at least 12 months were
      followed for a mean period of 39 (24-76) months. Their treatment efficacy was
      historically compared with that of 19 children (14 male; age, 2.1-17 y; mean, 10
      y) who had been treated with IFN-alpha and were followed for a mean period of 39
      (24-104) months. Therapeutic responses were compared at 2 y after the initiation
      of either of the treatment methods. RESULTS: Two years after the initiation of
      treatment, the results for children treated with lamivudine versus IFN-alpha were
      as follows: hepatitis B e antigen (HBeAg) seroconversion occurred in 26 (65%) of
      the 40 children versus 7 (37%) of the 19 children, P < 0.05. In the lamivudine
      treated group, the results for children treated before the age of 7 versus age >7
      were as follows: HBeAg seroconversion occurred in 17 (89%) of the 19 children
      versus 9 (43%) of the 21 children, P < 0.01, and loss of hepatitis B surface
      antigen (HBsAg) occurred in 8 (42%) versus 0%, P < 0.001. CONCLUSIONS: Long-term
      treatment of lamivudine led to significant improvement in the seroconversion rate
      of HBeAg in children with chronic hepatitis B compared with IFN-alpha therapy.
      Furthermore, in preschool-age children, it led to significant improvement in the
      seroconversion rate of HBeAg and HBsAg compared with school-age children.

PMID- 17204961
TI  - High prevalence of alpha-1-antitrypsin heterozygosity in children with chronic
      liver disease.
AB  - OBJECTIVE: Alpha-1-antitrypsin (A1AT) deficiency is the most common genetic cause
      of liver disease in children; however, the role of polymorphic heterogeneity in
      the A1AT gene as a modifier of other forms of pediatric liver disease is not
      clear. We hypothesized that non-M A1AT allele variants are more common in
      children with chronic liver disease than in the general population. METHODS: A
      retrospective, single-center study was performed in which A1AT phenotypes were
      obtained by reviewing charts of children with chronic liver disease. Chi-square
      analysis was used to compare allele frequencies in the population of children
      with liver disease with published epidemiologic data and to compare allele
      frequencies among disease subgroups. RESULTS: The frequency of A1AT Z and other
      alleles was increased in children with chronic liver disease (n = 241) when
      compared with the published reference database (P < 0.001). This increase
      remained significant when the population was divided into disease subsets:
      biliary atresia (n = 67) and other liver disease (n = 174) (P < 0.001 for both).
      Among children with biliary atresia referred for liver transplant evaluation, the
      presence of a non-M allele was associated with a lower mean age at transplant
      listing than the MM phenotype (235 vs 779 days, P = 0.036) and more frequent loss
      of native liver by 24 months of age (90% vs 65%, P = 0.04). CONCLUSIONS: A1AT non
      M alleles are more frequent in children with chronic liver disease than in the
      general population. We speculate that these non-M alleles may act as genetic
      modifiers in pediatric liver disease in general and modulate disease progression
      in children with biliary atresia in particular.

PMID- 17204962
TI  - Intrahepatic cystic lesions after hepatic portoenterostomy for biliary atresia
      with bile lake and dilated bile ducts.
AB  - BACKGROUND: Intrahepatic cystic lesions develop after hepatic portoenterostomy in
      some patients with biliary atresia and have been regarded as an indication of
      poor prognosis; however, there is confusion about the terminology and concepts of
      the lesions. We investigated whether the cystic lesions constituted a single
      entity. PATIENTS AND METHODS: From 1980 to 2005, we encountered 80 patients with
      biliary atresia. Abdominal ultrasonography disclosed intrahepatic cystic lesions
      in 20 (25%) patients after hepatic portoenterostomy. The cystic lesions were
      analyzed morphologically with radiologic imaging studies and histologically in 13
      patients who underwent liver transplantation. RESULTS: Fifteen patients had
      solitary simple cystic lesions, and 5 patients had multiple continuous oval or
      beaded lesions. Solitary lesions had a fibrotic cyst wall and lacked epithelia.
      Continuous lesions had a cyst wall covered with biliary epithelia. Thirteen
      patients with solitary cysts died or required liver transplantation. In 2
      patients with continuous lesions, surgical reboring of the porta hepatis could
      eliminate cystic lesions and jaundice. CONCLUSIONS: Intrahepatic cystic lesions
      include 2 different conditions. Solitary cysts are retention pseudocysts, which
      should be referred to as a bile lake, and are associated with poor prognosis.
      Continuous beaded cysts are dilated bile ducts, which may be reversed. This
      distinction is important when considering the treatment strategy.

PMID- 17204963
TI  - Paediatric Hepatology Dependency score (PHD score): an audit tool.
AB  - BACKGROUND: The aim was to develop a tool that measures patient dependency and
      disease severity in children with mild to severe liver disease. METHODS: The
      initial pilot score was based on known markers of disease severity in acute and
      chronic liver disease. Between 1997 and 2001, the score was modified 4 times and
      reduced to comprise 10 key parameters: aspartate transaminase, prothrombin time,
      albumin, bilirubin, ascites, nutritional support, organ dysfunction, blood
      product support, sepsis and intravenous access. The score's face validity,
      internal consistency, interobserver agreement and construct validity were
      evaluated statistically and by the use of endpoints such as survival and
      transplant after 6 months. RESULTS: The final 10 variable score was tested on 71
      children admitted over two 3-month periods. The Cronbach's alpha score (a test
      for internal consistency) for the total score was 0.72. Serial data paralleled
      clinical deterioration and response to interventions. A Paediatric Hepatology
      Dependency score >15 had an odds ratio of 7 (P = 0.0125) for death or transplant
      at 6 months. The score was also found to agree with the paediatric end-stage
      liver disease score for the 12 patients being listed for liver transplantation (r
      = 0.660, P < 0.05). CONCLUSION: The Paediatric Hepatology Dependency score is
      valid and internally consistent and is a convenient measure of dependency and
      disease severity in a heterogeneous group of patients with liver disease. It also
      allows admissions to be audited for comparison between eras and for monitoring
      the progress of patients while on the ward.

PMID- 17204964
TI  - Nutritional intake and status in children with cystic fibrosis: does age matter?
AB  - OBJECTIVES: To determine whether nutritional intake and status vary with age in
      children with cystic fibrosis (CF). METHODS: Case-control study examining
      differences in nutritional parameters and intakes in 58 children with CF
      recruited from a regional centre (2000-2001) and 45 controls. Participants were
      divided into age groups of 5-8 years, 9-12 years and 13-16 years. Weight, height,
      body mass index and standard deviation scores were recorded. A 4-day food diary
      (51 CF, 31 controls) was calculated for macronutrients and micronutrients.
      RESULTS: Energy intakes (%EAR) increased with age (112%, 115% and 116%,
      respectively) and were significantly higher in children with CF than controls.
      Lower weight and growth trends were observed in children ages 5 to 8 years (NS).
      Weight gain and growth was normal in children with CF ages 9 to 12 years but
      declined at 13 to 16 years (weight z score -0.85 vs 0.68 P = 0.003, height z
      score -0.54 vs 0.53 P = 0.002, body mass index z score -0.72 vs 0.41 P = 0.03).
      Lung function was the most significant predictor of nutritional status at 9 to 12
      years (r2 = 0.37, P = 0.006) and 13 to 16 years (r2 = 0.31, P = 0.01), but was
      not significant in children ages 5 to 8 years. CONCLUSION: Energy intakes
      increased with age in children with CF and exceeded that of healthy peers in all
      age groups. Weight gain and growth equaled that of healthy peers at 9 to 12 years
      but was suboptimal at 5 to 8 years and dramatically declines at 13 to 16 years.
      Energy intakes were unable to meet the clinical demands of children in these age
      groups. Both remain vulnerable and require greater nutritional targeting.

PMID- 17204965
TI  - Effects of high versus standard early protein intake on growth of extremely low
      birth weight infants.
AB  - OBJECTIVES: Early provision of protein has been shown to limit catabolism and
      could improve growth. Our objective was to determine whether early aggressive
      protein intake improved growth outcomes of extremely low birth weight (ELBW)
      infants. PATIENTS AND METHODS: ELBW infants were included in the study if they
      had no major congenital anomalies or renal failure and were still hospitalized at
      36 weeks postmenstrual age. In 25 infants (HP) the early protein intake was
      planned to be 20% greater than in 31 historical controls (SP). RESULTS: The 2
      groups were similar in the baseline characteristics. The mean protein intake
      during the first 14 days of life was significantly greater in the HP group (3.1
      +/- 0.2 vs 2.5 +/- 0.2 g/kg/d; P<0.0001). HP group showed lower postnatal weight
      loss (-3.1%; 95% confidence interval [CI] -5.9, -0.2) and earlier regain of birth
      weight (-4.1 days; 95% CI -6.6, -1.7). Mean blood urea nitrogen and bicarbonate
      levels were similar; mean serum glucose level was lower in the HP group (-21,7
      mg/dL; 95% CI -41.9,-1.5). HP infants had a reduced fall in weight z score (
      0.57; 95% CI -1.01, -0.12) and in length z score (-0.51; 95% CI -0.97, -0.05)
      from birth to discharge. CONCLUSION: Early high protein intake was associated
      with improved weight and length growth outcomes at discharge. These findings
      highlight the benefits of aggressive protein intake immediately after birth.

PMID- 17204966
TI  - Use of bioelectrical impedance analysis and anthropometry to measure fat-free
      mass in children and adolescents with Crohn disease.
AB  - OBJECTIVES: To investigate the precision of published prediction equations for
      fat-free mass (FFM) from bioimpedance measurements in children with Crohn disease
      using dual-energy X-ray absorptiometry (DXA) as an in vivo gold standard.
      METHODS: Fat-free mass of 49 white boys and girls ages 7.3 to 16.9 y suffering
      from Crohn disease was measured by DXA. Body weight, height and bioimpedance
      measurements were also collected. FFM measured by DXA (FFM(DXA)) was compared
      with FFM predicted by the only 5 published prediction equations available for
      children and adolescents. An equation was developed for predicting FFM and was
      validated using a bootstrap method. RESULTS: When correlating predicted FFM with
      FFM(DXA), Schaefer's equation showed the highest R2 (0.950), the smallest
      standard error of estimate (SEE) (2.05 kg) and the smallest percentage error
      (0.28%). Our prediction equation for estimating FFM was FFM = 0.652 Ht2/Z +
      0.0385 Wt + 0.586 Age - 0.327, R2 = 0.951, SEE = 2.08, P < 0.0005, where Ht2/Z is
      the impedance index in cm2/ohm, Wt is body weight in kilograms, age is in years.
      R2 value from bootstrap method was 0.950 +/- 0.01 (95% confidence interval 0.927
      0.968), indicating an acceptable validation of the derived formula. CONCLUSIONS:
      The formula of Schaefer is the best for predicting FFM. The present study
      provides a new prediction equation for estimating FFM in children with Crohn
      disease that may be used in clinical settings in which more sophisticated body
      composition measuring equipments are not available.

PMID- 17204967
TI  - Double-blind, placebo-controlled trial comparing effects of supplementation of
      two micronutrient sprinkles on fatty acid status in Cambodian infants.
AB  - BACKGROUND: Infants in developing countries require early dietary interventions
      to prevent nutritional deficiencies, above all protein, energy, iron and zinc. To
      what extent these interventions may affect the fatty acid (FA) status is still
      unknown. OBJECTIVES: To examine and compare the effects of 2 micronutrient
      "sprinkles" supplementations (iron 12.5 mg + folic acid 150 microg, iron/folate
      and iron 12.5 mg + folic acid 150 microg + zinc 5 mg + vitamins A, C and D3,
      mineral/micronutrient [MMN]) versus placebo on the FA status of Cambodian
      infants. METHODS: A total of 204 infants age 6 mo and living in Kompong Chhnang
      Province, Cambodia, were randomly assigned to receive daily supplementation of
      MMN (n = 68) and iron/folate (n = 68) or placebo (n = 68) for a 12-mo period in
      powder form as sprinkles. At the end of the intervention period, FAs in the range
      of 16 to 24 C were determined in blood drops absorbed on a strip collected from
      182 subjects, and values among the 3 intervention subgroups and those of 21
      Italian 18-mo-old, normal-growing infants as the reference group were compared.
      RESULTS: At the end of the supplementation trial, higher levels of the 2
      essential FAs (EFAs) (linoleic acid, 18:2n-6, and alpha-linolenic acid, 18:3n-3)
      were found in the MMN group. No differences occurred for the major longer chain
      derivatives of both EFAs arachidonic acid (20:4n-6) and docosahexaenoic acid
      (22:6n-3). In MMN supplemented Cambodians, blood levels of linoleic acid
      approached those of Italian infants, and in addition their alpha-linolenic acid
      levels were improved. Cambodian infants, mostly still breast-fed through the
      second year of life, showed significantly higher levels of long-chain derivatives
      of both the n-6 and the n-3 series compared with Italians. CONCLUSIONS:
      Supplementation with iron, folic acid, zinc and vitamins was associated with an
      increase of linoleic acid and alpha-linolenic acid levels in Cambodian infants
      versus placebo, without significant changes in the concentrations of their longer
      chain derivatives, resulting in a FA status closer to Italian counterparts for
      the essential polyunsaturated FA levels. The iron/folate-treated infants showed
      no differences compared with the other 2 groups. Studies are needed to
      differentiate the potential effects of the supplemented micronutrients on the FA
      status.

PMID- 17204968
TI  - Pulsatile hepatofugal flow in the portal vein: hallmark of a congenital
      hepatoportal arteriovenous fistula.

PMID- 17204969
TI  - Pancreatitis as the initial manifestation of stage IV neuroblastoma.

PMID- 17204970
TI  - Thrombotic microangiopathy in a child with acute pancreatitis.

PMID- 17204971
TI  - Pediatric gastrointestinal sarcoidosis presenting with protein-losing
      enteropathy.

PMID- 17204972
TI  - Studies on human rotavirus (HRV) vaccination.

PMID- 17204973
TI  - Nutritional solutions to major health problems of preschool children: how to
      optimise growth and development.

PMID- 17204974
TI  - Effect of infections and environmental factors on growth and nutritional status
      in developing countries.
AB  - Despite numerous advances and improvements in child health globally, malnutrition
      remains a major problem and underlies a significant proportion of child deaths. A
      large proportion of the hidden burden of malnutrition is represented by
      widespread single and multiple micronutrient deficiencies. A number of factors
      may influence micronutrient deficiencies in developing countries, including poor
      body stores at birth, dietary deficiencies and high intake of inhibitors of
      absorption such as phytates and increased losses from the body. Although the
      effects of poor intake and increased micronutrient demands are well described,
      the potential effects of acute and chronic infections on the body's micronutrient
      status are less well appreciated. Even more obscure is the potential effect of
      immunostimulation and intercurrent infections on the micronutrient distribution
      and homeostasis. The association therefore of relatively higher rates of
      micronutrient deficiencies with infectious diseases may be reflective of both
      increased predisposition to infections in deficient populations as well as a
      direct effect of the infection itself on micronutrient status indicators.
      Recently the association of increased micronutrient losses such as those of zinc
      and copper with acute diarrhea has been recognized and a net negative balance of
      zinc has been shown in zinc metabolic studies in children with persistent
      diarrhea. It is also recognized that children with shigellosis can lose a
      significant amount of vitamin A in the urine, thus further aggravating
      preexisting subclinical vitamin A deficiency. Given the epidemiological
      association between micronutrient deficiencies and diarrhea, supplementation
      strategies in endemic areas are logical. The growing body of evidence on the key
      role of zinc supplementation in accelerating recovery from diarrheal illnesses in
      developing countries supports its use in public health strategies.

PMID- 17204975
TI  - Nutritional deficiencies in learning and cognition.
AB  - The postinfancy period is crucial for normal brain development, providing
      subsequent optimal conditions for learning and cognition. Both iron deficiency
      and essential fatty acids deficiency may impair normal neurological development.
      This review examines the limited number of studies that have been performed in
      preschool children and offers a broader view of the relationships among
      nutrition, nutrients and cognition.

PMID- 17204976
TI  - Prevention and control of obesity in preschool children: importance of normative
      standards.

PMID- 17204977
TI  - Tackling the child malnutrition problem: from what and why to how much and how.
AB  - There is strong economic evidence to invest in improving the economic status of
      young children, yet programs remain underresourced. Returns on investment in
      child nutrition in terms of improved health, better education outcomes and
      increased productivity are substantial, and cost estimates for effective programs
      are in the range of $2.8 to $5.3 billion. These amounts are modest when compared
      with total international development assistance or current spending on luxury
      goods in wealthy nations. New initiatives to redefine nutrition science and to
      apply innovative problem-solving technologies to the global nutrition problem
      suggest that steps are being taken to accelerate progress toward a malnutrition
      free world.

PMID- 17204978
TI  - Nutritional solutions to major health problems of preschool children: how to
      optimise growth and development.
AB  - Despite major economic development in the last few decades, childhood nutrition
      remains a great challenge for the human species. A combination of undernutrition,
      overnutrition, and poor dietary quality affect to a variable extent all of the
      world's populations, and are often combined in the same areas and even in the
      same families. Malnutrition is part of the life of many individuals since
      conception and is transmitted by 1 generation to the next. Countries with lower
      income per capita and poor socioeconomic strata are mainly affected and, in turn,
      malnutrition hampers their development. The eradication of child malnutrition is
      crucial in the fight against poverty. This article examines whether this goal
      will be achieved within the time frame the United Nations has set.

PMID- 17204979
TI  - Successful food-based programmes, supplementation and fortification.
AB  - This review highlights interventions and delivery mechanisms to alleviate macro-
      and micronutrient deficiencies in preschool children. These deficiencies can be
      addressed through an integrated combination of improved dietary intake,
      supplementation, commercial and home-based fortification of complementary foods.
      Several developed and developing countries have implemented successful approaches
      to eliminate protein-energy malnutrition and micronutrient deficiencies with
      sustained impact. These include provision of oral supplements in capsule, tablet
      or syrup form. Certain micronutrients (eg, vitamin A) can be provided as high
      dose supplements twice per year. Most other vitamins and minerals (eg, iron,
      zinc, iodine) need to be provided in daily doses. Fortified complementary foods
      provided through public feeding programmes and commercially marketed foods have
      also made a positive impact. There is growing evidence of the impact of home
      based fortification of complementary foods using premixes in single-serving
      sachets. The fortification of commercially marketed staple foods such as cereal
      flours, cooking oils and dairy products could have a small but significant impact
      on preschool children. Cereal flours with iron, folic acid and other nutrients
      have expanded rapidly, with evidence of impact. A key need is to deliver
      micronutrients to remote and impoverished populations in an affordable and
      sustainable manner. Government commitment, clear policy and programme direction,
      advocacy and communication combined with a strong public-private partnership is
      essential for successful programmes. Often a period of voluntary fortification
      needs to be followed by mandatory requirement to ensure full compliance and
      sustained impact. The review concludes that proven technologies, communications
      and infrastructure can be harnessed to ensure that the nutrient needs of
      preschool children are met. When administered systematically with the commitment
      of and participation by the public and private sectors, most of the major
      deficiencies can be bridged on a sustained basis, contributing to improved health
      and well-being of millions of children around the world.

PMID- 17204980
TI  - Solutions to nutrition-related health problems of preschool children: education
      and nutritional policies for children.
AB  - OBJECTIVE: By reviewing the literature, lessons learned and experience regarding
      the nutrition-related health problems of preschool children, draw conclusions and
      make recommendations on education and nutrition policies for young children.
      RESULTS: The most common causes of under-5 mortality in low-income countries have
      been identified as neonatal disorders, diarrhoea, respiratory infections,
      malaria, measles, and in some developing countries, AIDS. More than half (56%) of
      all child deaths have underlying malnutrition and undernutrition as a
      contributing factor. Children must have optimal growth and physical and
      intellectual development to learn and achieve their potential in society.
      Solutions include both preventive and curative interventions at all levels and
      include both improved health and education systems. Recent focus has been on
      health systems interventions that address averting deaths by cause for the 42
      countries that account for 90% of worldwide under-5 deaths (the majority in sub
      Saharan Africa). However, parallel or multisectoral interventions must be
      addressed to all children at risk for death, poor health and compromised growth
      and development. Adequate health care and nutrition is a human right, legally
      established in the Convention on the Rights of the Child. CONCLUSIONS: Improved
      health and nutrition will lead to enhanced economic development, but having a
      poverty focus appears to be essential, if poor people are not to be marginalized
      further. The HIV/AIDS pandemic illustrates this challenge clearly. The role of
      education, especially girls' education, in improved health and nutrition status
      of children and birth-spacing is now clear, as is improving women's status.
      Increases in female status and education have been estimated to account for half
      of the reduction in child malnutrition rates during the past 25 years.

PMID- 17204981
TI  - Priorities in nutritional rehabilitation.
AB  - This review examines nutritional rehabilitation and stresses nutrition
      prophylaxis or prevention because for school-age children, health promotion and
      disease prevention are the keys to a healthy childhood.

PMID- 17204982
TI  - The Danone Institutes.

PMID- 17204983
TI  - Causes of nutrition-related public health problems of preschool children:
      available diet.
AB  - The primary goal of this review is to examine the timing and nature of dietary
      inadequacy during the first 5 years of life. An important issue is that many
      children in developing countries are already nutritionally depleted by the end of
      the first year of life, because maternal undernutrition can cause low fetal
      accumulation of nutrient stores and secretion of inadequate amounts of some
      micronutrients in breast milk. Improvement of maternal diet and micronutrient
      status is required to remedy this situation. During the period of complementary
      feeding, most households may be able to provide their young children with
      sufficient energy and protein from home-produced complementary foods, but many do
      not feed foods with an adequate energy density or a sufficient number of meals
      per day. Inadequate micronutrient intakes and resulting deficiencies are common
      in preschoolers because of a lack of sufficient animal source foods, and have
      been associated with delayed child development. Dietary diversity is an
      especially important determinant of micronutrient intakes when animal source food
      intake is low. Interventions with animal source foods have produced improvements
      in growth, micronutrient status, cognitive performance and activity of children.
      Although much is now known about the role of inadequate diets in preschooler
      malnutrition, on a global scale the ability of households to apply this knowledge
      to improve the diets of their children is still limited.

PMID- 17204984
TI  - A combined endoscopic and external approach for extraction of large stones with
      preservation of parotid and submandibular glands.

PMID- 17204985
TI  - Impact of re-resection for inadequate margins on the prognosis of upper
      aerodigestive tract cancer treated by laser microsurgery.
AB  - OBJECTIVES: Positive or uncertain surgical margins left untreated have a distinct
      prognostic relevance in squamous cell carcinoma of the upper aerodigestive tract.
      An advantage of transoral laser microsurgery is that it can be easily repeated if
      inadequate resection margins are found postoperatively. The present study
      investigates the impact of laser surgical reresection on the outcome of patients.
      STUDY DESIGN: The authors conducted a retrospective unicenter study. METHODS: A
      review of 1,467 patients with squamous cell carcinoma of the upper aerodigestive
      tract who were initially treated by transoral laser microsurgery with curative
      intent between August 1986 and December 2002 was conducted. Locoregional control
      as well as TNM adjusted and overall survival were analyzed using the Kaplan-Meier
      method. RESULTS: Three hundred eighty-six patients have required reresection to
      obtain clear surgical margins, in 70 of whom residual carcinoma has been detected
      in revision specimens. Patients without need for revision and those in whom
      revision specimens were found tumor-free had an almost identical locoregional
      control (P = .4611). In patients with positive revision specimens, however,
      locoregional control was significantly worsened (P = .0058). Neither the need for
      reresection nor the detection of further tumor tissue in revision specimens
      affected TNM adjusted or overall survival. CONCLUSIONS: Survival of patients was
      similar whether clear resection margins were reached within the first surgical
      step or with revision surgery. However, patients in whom reresection specimens
      contained residual carcinoma had an increased risk of locoregional failure and
      should undergo a further reresection or at least a very close follow up.

PMID- 17204986
TI  - Modeling the cholesteatoma microenvironment: coculture of HaCaT keratinocytes
      with WS1 fibroblasts induces MMP-2 activation, invasive phenotype, and
      proteolysis of the extracellular matrix.
AB  - BACKGROUND: Increased keratinocyte proliferation, increased keratinocyte
      migration, elaboration of proteases resulting in proteolysis of the extracellular
      matrix (ECM), and destruction of surrounding tissues all typify the course of
      cholesteatoma growth. The contribution of stromal fibroblasts to these behaviors
      remains relatively unexplored. OBJECTIVES: Our objective for the current studies
      was to create a simple model with which to study these cholesteatoma behaviors,
      specifically, cell migration, invasion, and proteolysis of the extracellular
      matrix as well as the role of fibroblasts in the activated keratinocyte phenotype
      of cholesteatoma. DESIGN: The authors conducted an in vitro culture model.
      METHODS: The resulting model consists of activated keratinocytes (HaCaT cells)
      cocultured with normal dermal fibroblasts (WS1 cells) within a three-dimensional
      reconstituted ECM. We used a confocal imaging assay and software analysis to
      quantify total functional proteolysis of the ECM in monotypic and organotypic
      cocultures. This was accomplished by growing cells on an artificial ECM comprised
      of Matrigel and DQ-collagen IV. DQ-collagen is a "quenched" fluorescent peptide
      whose fluorescence is unmasked by proteolytic cleavage. RESULTS: Organotypic
      cocultures of keratinocytes and fibroblasts exhibited increased cell migration,
      increased cell invasion, increased matrix metalloproteinase-2 secretion and
      activation, and increased proteolysis of type IV collagen in three-dimensional
      ECM. Exposure to NSC27366, inhibitor of the small GTPase, Rac, resulted in
      reduction in both cell invasion and ECM proteolysis. CONCLUSIONS: Stromal
      fibroblasts may stimulate the invasive phenotype of keratinocytes, including ECM
      proteolysis. Increased cell invasion and proteolysis are dependent on the Rac
      pathway in this model. This simple culture model may help further our
      understanding of these destructive behaviors in cholesteatoma keratinocytes.

PMID- 17204987
TI  - A potential portal flow in the inner ear.
AB  - OBJECTIVES/HYPOTHESIS: The aim of the present study was to visualize the flow
      direction of blood in the extraosseous part of the vein of the vestibular
      aqueduct (VVA) and to explore the effect of an induced obstruction in the distal
      part of the VVA before it merges with the sigmoid sinus. The endolymphatic sac
      has been implicated as a potential endocrine gland, which venules drain to the
      VVA. A reversal of the direction of flow in the VVA toward the inner ear could,
      through vestibular arteriovenous anastomosis, cause portal circulation in the
      inner ear. STUDY DESIGN: The authors conducted an experimental animal study using
      in vivo fluorescence microscopy. RESULTS: Obstructing the distal part of the VVA
      just before it empties into the sigmoid sinus immediately reverses the flow of
      blood in the VVA toward the inner ear. CONCLUSIONS: After an obstruction of the
      VVA, the drained venous blood from the endolymphatic sac may enter a portal
      circulation in the inner ear, which could cause disturbances in the endolymph
      homeostasis and potentially symptoms as seen in Meniere disease.

PMID- 17204988
TI  - Effects of 532 nm pulsed-KTP laser parameters on vessel ablation in the avian
      chorioallantoic membrane: implications for vocal fold mucosa.
AB  - OBJECTIVES: Selective vascular ablation (photoangiolysis) using pulsed lasers
      that target hemoglobin is an effective treatment strategy for many vocal fold
      lesions. However, vessel rupture with extravasation of blood reduces selectivity
      for vessels, which is frequently observed with the 0.45-ms, 585-nm pulsed dye
      laser. Previous studies have shown that vessel rupture is the result of
      vaporization of blood, an event that varies with laser pulse width and pulse
      fluence (energy per unit area). Clinical observations using a 532-nm wavelength
      pulsed potassium-titanyl-phosphate (KTP) laser revealed less laser-induced
      hemorrhage than the pulsed dye laser. This study investigated settings for the
      pulsed KTP laser to achieve selective vessel destruction without rupture using
      the avian chorioallantoic membrane under conditions similar to flexible
      laryngoscopic delivery of the laser in clinical practice. STUDY DESIGN: The chick
      chorioallantoic membrane offers convenient access to many small blood vessels
      similar in size to those targeted in human vocal fold. Using a 532-nm pulsed KTP
      laser, pulse width, pulse energy, and working distance from the optical delivery
      fiber were varied to assess influence on the ability to achieve vessel
      coagulation without vessel wall rupture. METHODS: Third-order vessels (n = 135)
      were irradiated: Energy (471-550 mJ), pulse width (10, 15, 30 ms), and fiber-to
      tissue distance (1 mm, 3 mm) were varied systematically. RESULTS: Selective
      vessel destruction without vessel wall rupture was more often achieved by
      increasing pulse width, increasing the fiber-to-tissue distance, and decreasing
      energy. Vessel destruction without rupture was consistently achieved using 15- or
      30-ms pulses with a fiber-to-tissue distance of 3 mm (pulse fluence of 13-16
      J/cm). CONCLUSIONS: This study substantiates our clinical observation that a 532
      nm pulsed KTP laser was effective for ablating microcirculation while minimizing
      vessel wall rupture and hemorrhage.

PMID- 17204989
TI  - Operating room versus office-based injection laryngoplasty: a comparative
      analysis of reimbursement.
AB  - BACKGROUND: Injection laryngoplasty (IL) continues to evolve as new indications,
      techniques, approaches, and injection materials are developed. Although
      historically performed under local or general anesthesia in the operating room
      suite, IL is now increasingly being performed in an office-based setting. This
      report presents the results of a reimbursement analysis comparing office-based
      versus operative IL. OBJECTIVE: The objective of this study was to compare the
      reimbursement of office-based injection laryngoplasty with the reimbursement of
      performing the same procedure in the operating room. DESIGN: The authors
      conducted reimbursement and outcome analysis through retrospective office chart
      and hospital record review. METHODS: A retrospective review was performed of the
      hospital records of patients having undergone injection laryngoplasty at the
      University of Pittsburgh Voice Center from July 1998 through March 2005. Group I
      included patients who underwent IL in the operating room, whereas group II
      included those who had office-based IL. A reimbursement analysis for both groups
      was then performed comparing surgeon fees, anesthesia, and hospital charges and
      reimbursement. The clinical efficacy of IL performed in either office versus
      operating room settings was measured by comparing the pre- and postintervention
      Voice Handicap Index-10 scores for all patients. A predictive model of potential
      cost savings is developed based on the results of the analysis. RESULTS: Average
      reimbursement was 2,505 dollars for group I (n = 108) and 496 dollars for group
      II (n = 50). This reimbursement differential was preserved across the various
      insurance types examined. There was no significant difference in Voice Handicap
      Index-10 change after surgery between group I and II. CONCLUSIONS: Office-based
      IL is both clinically and financially effective, providing patients with a
      convenient and flexible alternative to operating room-based intervention for
      glottal insufficiency.

PMID- 17204990
TI  - Endoscopic ligation of the anterior ethmoid artery.

PMID- 17204991
TI  - Electromyographic findings after different selective neck dissections.
AB  - OBJECTIVES: The objective was to compare electrophysiologic investigations of the
      upper trapezius muscle (UT) after different selective neck dissections (SND) and
      analyze the differences between types of SND and the preservation and excision of
      the cervical nerves (the C2-4 rami of the cervical plexus). STUDY DESIGN:
      Retrospective study of 54 patients (average age, 65.1 +/- 9.6 yr, 45 males) with
      70 SND. METHODS: Patients underwent needle electromyography (EMG) of the UT by 4
      months after surgery. The findings were rated according to the 5 point EMG scale
      system from 1 (total denervation: positive sharp wave or fibrillation potential
      at rest and electrical silence at voluntary contraction) to 5 (normal pattern).
      RESULTS: The average EMG scale was 1.7 +/- 1.1, 58.6% for score 1 and only 5.7%
      for score 5. There was not a significant difference in the EMG scale between the
      types of SND, whereas the group in which the cervical nerves were excised was
      significantly lower than in that in which it was preserved. The average EMG
      scales in the former and latter were 1.5 +/- 0.8 and 2.0 +/- 1.3, 68.8%.
      CONCLUSIONS: The study data confirm that complete or incomplete denervation of
      the UT was caused by axonal injury of the spinal accessory nerve, even though it
      was spared, because of traction of the nerve during neck dissection. Second, the
      excision of the C2 to 4 rami of the cervical plexus caused worse damage of the
      UT. It is suggested that it is important to preserve the cervical nerves to avoid
      denervation of the UT.

PMID- 17204992
TI  - Using a virtual reality temporal bone simulator to assess otolaryngology
      trainees.
AB  - OBJECTIVE: The objective of this study is to determine the feasibility of
      computerized evaluation of resident performance using hand motion analysis on a
      virtual reality temporal bone (VR TB) simulator. We hypothesized that both
      computerized analysis and expert ratings would discriminate the performance of
      novices from experienced trainees. We also hypothesized that performance on the
      virtual reality temporal bone simulator (VR TB) would differentiate based on
      previous drilling experience. STUDY DESIGN: The authors conducted a randomized,
      blind assessment study. METHODS: Nineteen volunteers from the Otolaryngology-Head
      and Neck Surgery training program at the University of Toronto drilled both a
      cadaveric TB and a simulated VR TB. Expert reviewers were asked to assess
      operative readiness of the trainee based on a blind video review of their
      performance. Computerized hand motion analysis of each participant's performance
      was conducted. RESULTS: Expert raters were able to discriminate novices from
      experienced trainees (P < .05) on cadaveric temporal bones, and there was a trend
      toward discrimination on VR TB performance. Hand motion analysis showed that
      experienced trainees had better movement economy than novices (P < .05) on the VR
      TB. CONCLUSION: Performance, as measured by hand motion analysis on the VR TB
      simulator, reflects trainees' previous drilling experience. This study suggests
      that otolaryngology trainees could accomplish initial temporal bone training on a
      VR TB simulator, which can provide feedback to the trainee, and may reduce the
      need for constant faculty supervision and evaluation.

PMID- 17204993
TI  - Interleukin-12 expression enhances vesicular stomatitis virus oncolytic therapy
      in murine squamous cell carcinoma.
AB  - OBJECTIVES: Replication-competent, vesicular stomatitis virus (VSV) has been
      demonstrated to be an effective oncolytic agent in a variety of malignant tumors.
      Cytokine gene transfer has also been used as immunomodulatory therapy for cancer.
      To test the use of combining these two approaches, an oncolytic VSV vector (rVSV
      IL12) was designed to express the murine interleukin 12 (IL12) gene. This
      cytokine-carrying oncolytic virus was compared with an analogous noncytokine
      carrying fusogenic virus (rVSV-F) in the treatment of murine SCC VII squamous
      cell carcinoma (SCC). STUDY DESIGN AND SETTING: The authors performed in vitro
      testing of recombinant VSV-F and recombinant VSV-IL12 in SCC cell lines. In vivo
      testing of multiple direct intratumoral injections of rVSV-F or rVSV-IL12 in an
      orthotopic floor of mouth murine model was performed. Each cell line was tested
      using rVSV-F or rVSV-IL12 at multiplicity of infection of 0.01. The ability of
      each virus to replicate was tested by real-time reverse transcriptase-polymerase
      chain reaction over 48 hours to determine viral copies of RNA. Cell survival was
      determined by MTT assay over 72 hours. IL12 expression by rVSV-IL12-treated cells
      was determined by enzyme-linked immunosorbent assay. RESULTS: Both viruses
      demonstrated similar infection efficiency, viral replication, and cytotoxicity in
      vitro. In an SCC VII orthotopic floor of mouth model in immunocompetent C3H/HeJ
      mice, multiple intratumoral injections with each virus caused a significant
      reduction in tumor volume when compared with saline injections alone. The rVSV
      IL12-treated tumors showed a striking reduction in tumor volume when compared
      with rVSV-F and saline-treated tumors (P < .005). This striking reduction in
      tumor volume translated into a substantial survival benefit in rVSV-IL12-treated
      animals. No treatment-related toxicity was observed in either group.
      CONCLUSION/SIGNIFICANCE: rVSV-IL12 is a novel oncolytic vesicular stomatitis
      virus that effectively expresses IL12 and significantly enhances the treatment of
      head and neck murine carcinoma. Such combined oncolytic and immunomodulatory
      strategies hold promise in the treatment of head and neck cancers.

PMID- 17204994
TI  - Blue nevi of the sinonasal mucosa: a report of two cases and review of the
      literature.
AB  - Blue nevi are uncommon melanocytic proliferations. They occur mostly in the skin
      and occasionally in mucosae. Blue nevi of the sinonasal mucosa are extremely rare
      with only two cases reported to date. We report two more cases and review the
      literature. Compared with sinonasal malignant melanomas, which usually present as
      symptomatic tumors, sinonasal blue nevi are asymptomatic lesions found
      incidentally. A biopsy is required for a definitive diagnosis. Although none of
      the four cases had recurrence, given a rare but possible occurrence of malignant
      transformation in cutaneous blue nevi, complete excision with follow up should be
      the treatment of choice.

PMID- 17204995
TI  - Oxybutynin for refractory hot flashes in cancer patients.
AB  - OBJECTIVE: There is little information available on the treatment of hot flashes
      in patients refractory to pharmaceutical interventions. Anecdotal evidence led to
      the use of oxybutynin for the management of hot flashes in refractory cancer
      patients; therefore, we performed a retrospective chart review of such patients
      to determine the effect of oxybutynin in treating hot flashes and to observe the
      side effects of the drug in these patients. DESIGN: A prospective database of all
      patients treated for hot flashes was started in July 2004 and was retrospectively
      analyzed as of March 2006. Also included were individual charts preceding July
      2004. Fifty-two patient charts were examined. Demographic information was
      obtained along with baseline severity and frequency of hot flashes, dose and
      duration of treatment with oxybutynin, patient response to oxybutynin, and side
      effects. RESULTS: More than 90% of patients analyzed were refractory to hot flash
      treatments before starting oxybutynin. Seventy percent of patients showed a
      partial or excellent response to oxybutynin. The duration of oxybutynin use
      ranged from 2 weeks to 5 years with more than half of patients currently on
      oxybutynin or taking oxybutynin for longer than 6 months. Of those patients who
      experienced an excellent or partial response to treatment, 12% stopped because of
      documented oxybutynin-related side effects within 4 weeks. CONCLUSION: Oxybutynin
      seems promising in the management of hot flashes with tolerable side effects in
      the majority of refractory patients. A placebo-controlled, randomized study is
      being developed to look more closely at the effectiveness of oxybutynin in
      reducing hot flashes.

PMID- 17204996
TI  - Measuring aortic diameter improves accuracy of esophageal Doppler in assessing
      fluid responsiveness.
AB  - OBJECTIVE: Fluid responsiveness requires the accurate measurement of cardiac
      output that can be approached by aortic blood flow (ABF) as measured by
      esophageal Doppler monitoring (EDM). EDM devices may either include an echo
      determination of aortic diameter or estimate aortic diameter from nomograms and
      thus consider it as constant. However, it is unclear if measuring aortic diameter
      increases the accuracy of EDM to identify fluid responsiveness. Aortic diameter
      varies with arterial pressure such that its measure could be essential for
      assessing the changes in ABF during acute circulatory failure. We attempted to
      demonstrate that measuring aortic diameter improved the accuracy of EDM to assess
      fluid responsiveness. DESIGN: Prospective study. SETTING: University hospital
      intensive care unit. PATIENTS: Seventy-six patients with acute circulatory
      failure in whom a fluid challenge was given. INTERVENTIONS: Rapid volume
      expansion (500 mL of NaCl 0.9%). MEASUREMENTS AND MAIN RESULTS: We measured
      aortic velocity and area by EDM before and after fluid loading and evaluated the
      effects of fluid challenge on ABF, either measured after fluid infusion (measured
      ABFafter) or estimated assuming an unchanging aortic area (estimated ABFafter).
      If measured ABFafter was used for assessing fluid response, it was increased
      above 15% compared with ABF at baseline in 41 patients (responders). Conversely,
      estimated ABFafter increased above 15% from ABF at baseline in 27 patients only;
      that is, the effects of the challenge were underestimated in 14 patients. In
      these 14 patients, the relative change in mean arterial pressure during volume
      expansion was of greater magnitude than in patients who were classified as
      nonresponders by considering measured ABFafter. CONCLUSIONS: Monitoring the
      changes in aortic diameter improves the accuracy of EDM in assessing the
      hemodynamic effects of a fluid challenge, especially if it induces a large
      increase in arterial pressure. Estimating rather than measuring the aortic
      diameter may lead to underestimation of fluid responsiveness.

PMID- 17204997
TI  - Transforming growth factor-beta1 blocks in vitro cardiac myocyte depression
      induced by tumor necrosis factor-alpha, interleukin-1beta, and human septic shock
      serum.
AB  - OBJECTIVE: Serum from patients with septic shock induces depression of myocyte
      contractility in vitro that is proportional the reduction of ejection fraction in
      vivo. This effect is mediated, in part, by tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-1beta. Transforming growth factor (TGF)-beta is an
      immunomodulatory cytokine with a broad range of anti-inflammatory effects. Using
      an in vitro assay, this study sought to determine the effect of TGF-beta1 on
      myocyte depression induced by TNF-alpha, IL-1beta, and serum with known
      depressant activity from patients with septic shock. DESIGN: The maximum extent
      of shortening of electrically paced rat cardiac myocytes in tissue culture was
      quantified by a closed-loop video tracking system. Myocytes were exposed to
      different combinations of TNF-alpha, IL-1beta, septic serum, and TGF-beta1.
      SETTING: Basic research laboratory. MEASUREMENTS AND MAIN RESULTS: Increasing
      concentrations of TNF-alpha and IL-1beta each caused significant depression of
      maximum extent of myocyte shortening in vitro over 30 mins (p<.0001). Similarly,
      a synergistic combination of TNF-alpha and IL-1beta as well as serum with known
      depressant activity from five patients with acute septic shock induced
      significant depression of cardiac myocyte contraction (p<.01). Increasing
      concentrations of TGF-beta1 alone had no effect on maximum extent of cardiac
      myocyte contraction. However, myocytes that were co-incubated with increasing
      concentrations of TGF-beta1 demonstrated dose-dependent reversal of depression
      induced by TNF-alpha or IL-1beta (p<.0001). Similarly, depressant effects caused
      by synergistic concentrations of TNF-alpha and IL-1beta and serum from all five
      patients with septic shock were prevented by co-incubation with TGF-beta1.
      CONCLUSIONS: These data demonstrate that depression of in vitro cardiac myocyte
      contraction induced by proinflammatory cytokines and septic serum can be blocked
      by TGF-beta1. TGF-beta1 may have potential as therapy for sepsis-associated
      myocardial depression in humans.

PMID- 17204998
TI  - Co-infection with two Chlamydophila species in a case of fulminant myocarditis.
AB  - OBJECTIVE: The aim of this study is to describe a case of fulminant myocarditis
      caused by co-infection with Chlamydophila pneumoniae and Chlamydophila psittaci
      in order to facilitate diagnosis and clinical management of patients suffering
      from this rare but life-threatening condition. DESIGN: Case report. SETTING:
      Intensive care unit of Innsbruck Medical University. PATIENT: A 24-yr-old patient
      admitted with septicemia and cardiac failure. INTERVENTIONS: Cardiopulmonary
      resuscitation, extracorporal membrane oxygenation, implantation of an
      extracorporal cardiac assist device, and antibiotic treatment with erythromycin.
      MEASUREMENTS AND MAIN RESULTS: Cp. pneumoniae and Cp. psittaci were identified by
      means of polymerase chain reaction and electron microscopy in the patient's
      myocytes. Successful weaning off the ventricular assist device was performed
      within 2 wks after commencement of antibiotic therapy. CONCLUSIONS: This case
      report demonstrates co-infection with Cp. pneumoniae and Cp. psittaci to be a
      hitherto unknown cause of fulminant myocarditis. There is a particular risk of
      misdiagnosis of viral myocarditis, which must be avoided. Patients should be
      transferred to a center where extracorporal membrane oxygenation therapy and
      molecular diagnosis of all members of the family Chlamydiaceae are available.

PMID- 17204999
TI  - Reduced monocyte CD86 expression in postinflammatory immunodeficiency.
AB  - OBJECTIVE: Major surgery, polytrauma, stroke, and pancreatitis frequently lead to
      a compensatory anti-inflammatory response syndrome that often predisposes
      patients to lethal infections. This temporary postinflammatory immunodeficiency
      is characterized by altered function of blood monocytes. These cells show
      strongly reduced inflammatory and antigen-presentation capacity. Diminished
      monocyte expression of the major histocompatibility complex class II molecule
      human leukocyte antigen (HLA)-DR is a well-established diagnostic marker of this
      immunodeficiency. To further characterize the monocytic cells in this clinical
      state, we analyzed their expression of CD86, the most important co-stimulatory
      molecule. DESIGN: Analysis of blood samples that entered the clinical immunologic
      diagnostics and of cells from an in vitro model of postinflammatory
      immunodeficiency. SETTING: University laboratory. SUBJECTS: Healthy donors and
      intensive care unit (ICU) patients at the university hospital. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: The expression of HLA-DR on monocytes and of
      CD86 and CD80 on monocytes and B cells was analyzed by flow cytometry. Messenger
      RNA expression of CD86 was analyzed in isolated monocytes by real-time polymerase
      chain reaction on reverse transcribed. The normal range of monocyte CD86
      expression in healthy subjects was established to be from 2128 to 5102 surface
      molecules per cell and was independent of age, gender, and leukocyte and monocyte
      count. The CD86 expression on monocytes in ICU patients correlated with HLA-DR
      expression. Approximately 40% of the ICU patients with long-term reduced monocyte
      HLA-DR expression had a long-term reduction of CD86 expression. Patients in whom
      the expression of both molecules was diminished had an unfavorable prognosis. The
      diminished number of CD86 surface molecules on monocytes was associated with
      reduced CD86 messenger RNA levels in these cells. The expression of CD86 in B
      cells was not diminished in immunodeficient patients. The expression of CD80 in
      both monocytes and B-cells was minimal in healthy donors and not clearly changed
      in patients. CONCLUSIONS: The monocyte CD86 expression may be a helpful
      diagnostic variable in ICU patients.

PMID- 17205000
TI  - Prognostication during physician-family discussions about limiting life support
      in intensive care units.
AB  - OBJECTIVE: Prognostic information is important to the family members of
      incapacitated, critically ill patients, yet little is known about what prognostic
      information physicians provide. Our objectives were to determine the types of
      prognostic information provided to families of critically ill patients when
      making major end-of-life treatment decisions and to identify factors associated
      with more physician prognostication. DESIGN: Multiple-center, cross-sectional
      study. SETTING: ICUs of four hospitals. SUBJECTS: Thirty-five physicians, 51
      patients, and 169 family members. INTERVENTIONS: We audiotaped 51 physician
      family conferences in which there were deliberations about major end-of-life
      treatment decisions at four hospitals in 2000-2002. Conferences were coded to
      identify the types of prognostic information provided by physicians. We used a
      mixed-effects regression model to identify factors associated with more
      prognostication by physicians. MEASUREMENTS AND MAIN RESULTS: The mean number of
      prognostic statements per conference was 9.4+/-6.4 (range 0-29). Eighty-six
      percent of conferences contained discussion of the patient's anticipated
      functional status or quality of life, compared with 63% in which the chances for
      survival were discussed (p=.01). There were significantly more statements about
      prognosis for functional outcomes per conference compared with statements about
      prognosis for survival (median 4 [interquartile range 2-8] vs. 1 [interquartile
      range 0-3]; p<.001). Increasing educational level of the family was independently
      associated with more prognostic statements by physicians (p<.001) as was the
      degree of physician-family conflict about withdrawing life support (p<.001) and
      the physician's race being white (p=.009). CONCLUSIONS: Prognostication occurred
      frequently during physician-family deliberations about whether to forego life
      support, but physicians did not discuss the patient's prognosis for survival in
      more than one third of conferences. Less educated families received less
      information about prognosis. Future studies should address whether these
      observations partially explain the high prevalence of family misunderstandings
      about prognosis in intensive care units.

PMID- 17205001
TI  - Nurse-physician perspectives on the care of dying patients in intensive care
      units: collaboration, moral distress, and ethical climate.
AB  - OBJECTIVE: To explore registered nurses' and attending physicians' perspectives
      on caring for dying patients in intensive care units (ICUs), with particular
      attention to the relationships among moral distress, ethical climate,
      physician/nurse collaboration, and satisfaction with quality of care. DESIGN:
      Descriptive pilot study using a survey design. SETTING: Fourteen ICUs in two
      institutions in different regions of Virginia. SUBJECTS: Twenty-nine attending
      physicians who admitted patients to the ICUs and 196 registered nurses engaged in
      direct patient care. INTERVENTIONS: Survey questionnaire. MEASUREMENTS AND MAIN
      RESULTS: At the first site, registered nurses reported lower collaboration
      (p<.001), higher moral distress (p<.001), a more negative ethical environment
      (p<.001), and less satisfaction with quality of care (p=.005) than did attending
      physicians. The highest moral distress situations for both registered nurses and
      physicians involved those situations in which caregivers felt pressured to
      continue unwarranted aggressive treatment. Nurses perceived distressing
      situations occurring more frequently than did physicians. At the second site, 45%
      of the registered nurses surveyed reported having left or considered leaving a
      position because of moral distress. For physicians, collaboration related to
      satisfaction with quality of care (p<.001) and ethical environment (p=.004); for
      nurses, collaboration was related to satisfaction (p<.001) and ethical climate
      (p<.001) at both sites and negatively related to moral distress at site 2
      (p=.05). Overall, registered nurses with higher moral distress scores had lower
      satisfaction with quality of care (p<.001), lower perception of ethical
      environment (p<.001), and lower perception of collaboration (p<.001).
      CONCLUSIONS: Registered nurses experienced more moral distress and lower
      collaboration than physicians, they perceived their ethical environment as more
      negative, and they were less satisfied with the quality of care provided on their
      units than were physicians. Provider assessments of quality of care were strongly
      related to perception of collaboration. Improving the ethical climate in ICUs
      through explicit discussions of moral distress, recognition of differences in
      nurse/physician values, and improving collaboration may mitigate frustration
      arising from differences in perspective.

PMID- 17205002
TI  - Can physiological variables and early warning scoring systems allow early
      recognition of the deteriorating surgical patient?
AB  - OBJECTIVE: Early warning scoring systems are widely used in clinical practice to
      allow early recognition of the deteriorating patient, but they lack validation.
      We aimed to test the ability of physiologic variables, either alone or in
      existing early scoring systems, to predict major deterioration in a patient's
      condition and attempt to derive functions with superior accuracy. DESIGN: A
      comparative cohort study. SETTING: A teaching hospital in Scotland. PATIENTS: Two
      cohorts of general surgical high-dependency patients. The cohorts are a group of
      surgical high-dependency care patients who did not require intensive care
      admission and another group of patients who did require admission. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Prospective physiologic data on consecutive
      surgical high-dependency unit patients were collected and compared with
      physiologic data on patients admitted to the intensive care unit from the same
      surgical high-dependency units. Data were quality checked and summarized, and
      discriminant analysis and receiver operator curves were used to discriminate
      between the groups. There were significant physiologic differences between groups
      with regard to heart rate (p<.001, area under the receiver operating
      characteristic curve [AUC] 0.7), respiratory rate (p<.001, AUC 0.71), and oxygen
      saturation (p<.001, AUC 0.78) across time points. This was not present for
      systolic blood pressure or temperature. Existing early warning scoring systems
      had good discriminatory power (AUC 0.83-0.86). We derived discriminant functions,
      which have a high predictive ability to determine differences between groups
      (p<.0001, AUC 0.86-0.90). We found that heart rate and respiratory rate could
      detect differences between groups at 6 and 8 hrs before ICU admission, but oxygen
      saturation and the discriminant function 2 could detect differences 48 hrs before
      ICU admission. CONCLUSIONS: Some commonly used physiologic variables have
      reasonable power in determining the difference between patients requiring
      intensive care unit admission, but others are poor. Existing early warning scores
      have comparatively good discriminatory power. We have derived functions with
      excellent predictive power in this derivation cohort.

PMID- 17205003
TI  - Alcohol dependence is independently associated with sepsis, septic shock, and
      hospital mortality among adult intensive care unit patients.
AB  - OBJECTIVE: To determine the association between alcohol dependence (alcoholism
      not in remission and/or alcohol withdrawal) and sepsis, septic shock, and
      hospital mortality among intensive care unit (ICU) patients. DESIGN:
      Retrospective cohort study. SETTING: Two ICUs in an urban hospital. PATIENTS:
      Patients included 11,651 adult admissions to Denver Health Medical Center from
      January 1, 1999, to December 31, 2004, with >or=1 ICU day. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Of first admissions appearing in the data set
      (n=9,981), 1,222 (12.2%) had a diagnosis consistent with alcohol dependence.
      These patients had higher rates of sepsis (12.9% vs. 7.6%, p<.001), organ failure
      (67.3% vs. 45.8%, p<.001), septic shock (3.6% vs. 2.1%, p=.001), and hospital
      mortality (9.4% vs. 7.5%, p=.022) on unadjusted analyses. Patients with alcohol
      dependence also had fewer hospital-free days. After adjustment for factors with
      known association with sepsis, alcohol dependence was associated with sepsis.
      This association was modified if the patient received (adjusted odds ratio, 0.92;
      95% confidence interval, 0.65-1.31) or did not receive (adjusted odds ratio,
      1.91; 95% confidence interval, 1.49-2.44) red cell transfusions. A general
      predisposition to infections mediated some, but not all, of this association.
      Results were similar when repeat admissions were included in the analysis.
      Alcohol dependence was also associated with septic shock and hospital mortality
      in multivariable analyses. Among those with liver disease and sepsis, alcohol
      dependence was associated with more than two-fold increased risk-adjusted odds of
      hospital mortality (adjusted odds ration, 2.31; 95% confidence interval, 1.26
      4.24). Similarly, sepsis and liver disease carried higher odds of death for
      alcohol-dependent patients than for those without alcohol dependence.
      CONCLUSIONS: Alcohol dependence is independently associated with sepsis, septic
      shock, and hospital mortality among ICU patients. The underlying mechanisms of
      this association require exploration, as an increased rate of infections mediated
      some, but not all, of this association.

PMID- 17205004
TI  - Cardiac troponins in the intensive care unit: common causes of increased levels
      and interpretation.
AB  - BACKGROUND AND OBJECTIVES: Clinical chemistry is an important component of the
      diagnosis of many conditions, and advances in laboratory science have brought
      many new diagnostic tools to the intensive care unit clinician, including new
      biomarkers of cardiac injury like troponin T and I. Interpretation of these
      clinical laboratory results requires knowledge of the performance of these tests.
      SETTING AND PATIENTS: This article reviews the interpretation and performance of
      diagnostic markers of myocardial injury in patients with diverse clinical
      conditions of interest to critical care practitioners. CONCLUSIONS: Cardiac
      troponin I and T, regulatory components of the contractile apparatus, are
      sensitive indicators of myocardial injury and have become central to the
      diagnosis of myocardial infarction. The troponins are also released in a number
      of clinical situations in which thrombotic complications of coronary artery
      disease and resultant acute myocardial infarction have not occurred. These
      situations include conditions like pulmonary embolism, sepsis, myocarditis, and
      acute stroke. Elevated troponins in these conditions are thought to emanate from
      injured myocardial cells and, in most circumstances, have been associated with
      adverse outcomes. Practitioners should be mindful of the wide spectrum of
      diseases that may result in elevated troponin when interpreting these
      measurements.

PMID- 17205005
TI  - Daily sedative interruption in mechanically ventilated patients at risk for
      coronary artery disease.
AB  - OBJECTIVES: To determine the prevalence of myocardial ischemia in mechanically
      ventilated patients with coronary risk factors and compare periods of sedative
      interruption vs. sedative infusion. DESIGN: Prospective, blinded observational
      study. SETTING: Medical intensive care unit of tertiary care medical center.
      PATIENTS: Intubated, mechanically ventilated patients with established coronary
      artery disease risk factors. INTERVENTIONS: Continuous three-lead Holter monitors
      with ST-segment analysis by a blinded cardiologist were used to detect myocardial
      ischemia. Ischemia was defined as ST-segment elevation or depression of >0.1 mV
      from baseline. MEASUREMENTS AND MAIN RESULTS: Comparisons between periods of
      awakening from sedation vs. sedative infusion were made. Vital signs,
      catecholamine levels, and time with ischemia detected by Holter monitor during
      the two periods were compared. Heart rate, mean arterial pressure, rate-pressure
      product, respiratory rate, and catecholamine levels were all significantly higher
      during sedative interruption. Eighteen of 74 patients (24%) demonstrated ischemic
      changes. Patients with myocardial ischemia had a longer intensive care unit
      length of stay (17.4+/-17.5 vs. 9.6+/-6.7 days, p=.04). Despite changes in vital
      signs and catecholamine levels during sedative interruption, fraction of ischemic
      time did not differ between the time awake vs. time sedated [median
      [interquartile range] of 0% [0, 0] compared with 0% [0, 0] while they were
      sedated [p=.17]). The finding of similar fractions of ischemic time between awake
      and sedated states persisted with analysis of the subgroup of 18 patients with
      ischemia. CONCLUSIONS: Myocardial ischemia is common in critically ill
      mechanically ventilated patients with coronary artery disease risk factors. Daily
      sedative interruption is not associated with an increased occurrence of
      myocardial ischemia in these patients.

PMID- 17205006
TI  - A view from the other side.
AB  - OBJECTIVE: The environment in our intensive care units (ICUs) often serves the
      convenience of the staff who work in the ICU, rather than the critically ill
      patients and their loved ones who are, as a family unit, the objects of our care.
      OBSERVATIONS: Critically ill patients, especially those with high acuity, require
      close bedside attention. Continuous monitoring, frequent physical evaluations,
      invasive procedures, and other demands of bedside care are just some of the
      processes in the ICU that require heightened attention from ICU clinicians. But
      the fact that we "have a lot to do" at the bedside of critically ill patients has
      led to an unfortunate environment in many ICUs, one in which the needs of
      families are not only considered secondary to the convenience of ICU personnel,
      but are frequently dismissed as burdensome, unreasonable, and even counter to
      good-quality patient care. Perhaps this is why there are reports in the
      literature of family concerns about less than satisfactory interactions with ICU
      clinicians. The attitude we have toward families is an important part of the care
      we offer to patients in the ICU, and it can have a profound effect on the health
      of our patients' families. In palliative care circles, it has long been
      understood that the "unit of care" is both the patient and the family. Although
      we are moving in that direction in critical care, many ICUs may not always
      reflect an appreciation of the therapeutic potential or devastating consequences
      of the attitudes in the ICU. CONCLUSION: The evolution of our understanding of
      care for critical illness should include a different approach to families and
      visiting hours in the ICU. One that balances the need of family members to be
      with their loved ones at a time of critical illness and the need of ICU
      clinicians to conduct efficient bedside care.

PMID- 17205007
TI  - Clinical practice guidelines for support of the family in the patient-centered
      intensive care unit: American College of Critical Care Medicine Task Force 2004
      2005.
AB  - OBJECTIVE: To develop clinical practice guidelines for the support of the patient
      and family in the adult, pediatric, or neonatal patient-centered ICU.
      PARTICIPANTS: A multidisciplinary task force of experts in critical care practice
      was convened from the membership of the American College of Critical Care
      Medicine (ACCM) and the Society of Critical Care Medicine (SCCM) to include
      representation from adult, pediatric, and neonatal intensive care units.
      EVIDENCE: The task force members reviewed the published literature. The Cochrane
      library, Cinahl, and MedLine were queried for articles published between 1980 and
      2003. Studies were scored according to Cochrane methodology. Where evidence did
      not exist or was of a low level, consensus was derived from expert opinion.
      CONSENSUS PROCESS: The topic was divided into subheadings: decision making,
      family coping, staff stress related to family interactions, cultural support,
      spiritual/religious support, family visitation, family presence on rounds, family
      presence at resuscitation, family environment of care, and palliative care. Each
      section was led by one task force member. Each section draft was reviewed by the
      group and debated until consensus was achieved. The draft document was reviewed
      by a committee of the Board of Regents of the ACCM. After steering committee
      approval, the draft was approved by the SCCM Council and was again subjected to
      peer review by this journal. CONCLUSIONS: More than 300 related studies were
      reviewed. However, the level of evidence in most cases is at Cochrane level 4 or
      5, indicating the need for further research. Forty-three recommendations are
      presented that include, but are not limited to, endorsement of a shared decision
      making model, early and repeated care conferencing to reduce family stress and
      improve consistency in communication, honoring culturally appropriate requests
      for truth-telling and informed refusal, spiritual support, staff education and
      debriefing to minimize the impact of family interactions on staff health, family
      presence at both rounds and resuscitation, open flexible visitation, way-finding
      and family-friendly signage, and family support before, during, and after a
      death.

PMID- 17205008
TI  - Hypertonic saline reverses stiffness in a Sprague-Dawley rat model of acute
      intestinal edema, leading to improved intestinal function.
AB  - INTRODUCTION: Acute edema induced by resuscitation and mesenteric venous
      hypertension impairs intestinal transit and contractility and reduces intestinal
      stiffness. Pretreatment with hypertonic saline (HS) can prevent these changes.
      Changes in tissue stiffness have been shown to trigger signaling cascades via
      stress fiber formation. We proposed that acute intestinal edema leads to a
      decrease in intestinal transit that may be mediated by changes in stiffness,
      leading to stress fiber formation and decreased intestinal transit. Furthermore,
      HS administration will abolish these detrimental effects of edema. RESULTS:
      Intestinal edema causes a significant increase in tissue water and a significant
      decrease in intestinal transit and stiffness compared with sham. HS reversed
      these changes to sham levels. In addition, tissue edema led to significant stress
      fiber formation and decreased numbers of focal contacts. HS preserved tissue
      stiffness, prevented stress fiber formation, and was associated with improved
      intestinal function. CONCLUSION: HS eliminates intestinal tissue edema formation
      and improves intestinal transit. In addition, the action of HS may be mediated
      through its preservation of tissue stiffness, which leads to prevention of
      signaling via stress fiber formation, leading to preserved intestinal function.
      Finally, intestinal edema may provide a novel physiologic model for examining
      stiffness and stress fiber signaling.

PMID- 17205009
TI  - The effect of statin therapy on infection-related mortality in patients with
      atherosclerotic diseases.
AB  - OBJECTIVE: Statins have pleiotropic effects that are independent of their lipid
      lowering ability. We have previously shown that prior statin therapy is
      associated with a decreased risk of severe sepsis in patients admitted with acute
      bacterial infection. The aim of this study was to determine whether statin
      therapy is associated with a decreased risk of infection-related mortality.
      DESIGN: A prospective, observational, population-based study. SETTING: Tertiary
      university medical center. PATIENTS: Using a computerized database, 11,490
      patients with atherosclerotic diseases were identified and followed for up to 3
      yrs. Two groups of patients were compared: those receiving statins in the final
      month before follow-up termination and those who were not. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The primary outcome was infection-related
      mortality. Of the 11,362 patients included in the final analysis, 5,698 (50.1%)
      belonged to the statin group. Median follow-up was 19.8 months (interquartile
      range, 14.3-33.3). The risk of infection-related mortality was significantly
      lower in the statin compared with the no-statin group (0.9% vs. 4.1%), reflecting
      a relative risk of 0.22 (95% confidence interval, 0.17-0.28). Stepwise Cox
      proportional hazard survival analysis including a propensity score for receiving
      statins revealed that the protective effect of statins adjusted for all known
      potential confounders remained highly significant (hazard ratio, 0.37; 95%
      confidence interval, 0.27-0.52). CONCLUSIONS: Therapy with statins may be
      associated with a reduced risk of infection-related mortality. This protective
      effect is independent of all known comorbidities and dissipates when the
      medication is discontinued. If this finding is supported by prospective
      controlled trials, statins may play an important role in the primary prevention
      of infection-related mortality.

PMID- 17205010
TI  - Emergency preservation and delayed resuscitation allows normal recovery after
      exsanguination cardiac arrest in rats: a feasibility trial.
AB  - OBJECTIVE: Emergency preservation and resuscitation (EPR) comprise a novel
      approach for resuscitation of exsanguination cardiac arrest victims. EPR uses a
      cold aortic flush to induce deep hypothermic preservation, followed by
      resuscitation with cardiopulmonary bypass. Development of a rat EPR model would
      enable study of the molecular mechanisms of neuronal injury and the screening of
      novel agents for emergency preservation. DESIGN: A prospective, randomized study.
      SETTING: University research facility. SUBJECTS: Adult male Sprague-Dawley rats.
      INTERVENTIONS: Isoflurane-anesthetized rats were subjected to lethal hemorrhage
      (12.5 mL for 5 mins), followed by KCl-induced cardiac arrest and 1 min of no
      flow. Three groups (n=6) were studied: hypothermic EPR (H-EPR; 0 degrees C flush;
      target temperature, 15 degrees C); normothermic EPR (N-EPR; 38 degrees C flush);
      and controls. After 20 mins of H-EPR or N-EPR, resuscitation was initiated with
      cardiopulmonary bypass for 60 mins and mechanical ventilation. Controls were
      subjected to complete experimental preparation and anesthesia without cardiac
      arrest, followed by 60 mins of cardiopulmonary bypass and mechanical ventilation.
      Surviving rats were extubated 2 hrs later. Survival, Overall Performance Category
      (1, normal; 5, death), Neurologic Deficit Score, Histologic Damage Score, and
      biochemistry were assessed in survivors on day 7. MEASUREMENTS AND MAIN RESULTS:
      All rats in H-EPR and control groups survived, whereas none of the rats in the N
      EPR group had restoration of spontaneous circulation. All rats in the H-EPR and
      control groups achieved Overall Performance Category 1, normal Neurologic Damage
      Score, and normal or near normal Histologic Damage Score and biochemical markers
      of organ injury. CONCLUSIONS: We have established an EPR model in rats showing no
      neurologic injury, despite an exsanguination cardiac arrest, followed by 20 mins
      of EPR using miniaturized cardiopulmonary bypass. Establishment of this model
      should facilitate application of molecular tools to study the effects of
      hypothermic preservation and reperfusion and to screen novel pharmacologic
      adjuncts.

PMID- 17205011
TI  - Ventilator-associated pneumonia: breaking the vicious circle of antibiotic
      overuse.
AB  - OBJECTIVE: To assess the rate of appropriateness of empirical antimicrobial
      therapy for ventilator-associated pneumonia, to evaluate de-escalation in
      patients with ventilator-associated pneumonia treated according to local pathway,
      and to identify the bacteria responsible for recurrence of ventilator-associated
      pneumonia. DESIGN: Prospective observational study during a 36-month period.
      SETTING: Medical-surgical intensive care unit of a university hospital. PATIENTS:
      One hundred and fifteen patients hospitalized in an intensive care unit
      developing ventilator-associated pneumonia with positive cultures. The patients
      with ventilator-associated pneumonia were treated with limited-spectrum
      antibiotics (i.e., without activity against Pseudomonas aeruginosa) if they had
      no prior hospitalization (within 21 days) or prior administration of antibiotics
      (within 10 days). Quantitative cultures obtained by bronchoscopy or tracheal
      aspiration were used to reassess empirical therapy. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: A limited-spectrum therapy was used in 79 patients
      (69%). Empirical antimicrobial therapy was appropriate in 100 patients (85%). The
      mortality rate was significantly higher in the patients in whom empirical therapy
      was inappropriate than in those in whom treatment was appropriate (47 vs. 20%,
      p=.04). De-escalation was done in respectively 26% and 72% of patients with early
      and late-onset ventilator-associated pneumonia, whereas treatment was escalated
      in 27 patients (23%). Ventilator-associated pneumonia episodes were recurrent in
      22 cases, including eight episodes due to high-risk bacteria. CONCLUSIONS: A
      rational empirical antimicrobial therapy for ventilator-associated pneumonia
      using limited-spectrum antibiotics is possible if local ecology and patient
      medical history and clinical status are considered. In addition, de-escalation is
      feasible in 42% of patients. This integrative approach may reduce the emergence
      of resistant bacteria, which in turns reduces the need for broad-spectrum
      antibiotics, breaking the vicious circle of antibiotic overuse.

PMID- 17205012
TI  - Visiting hours policies in New England intensive care units: strategies for
      improvement.
AB  - OBJECTIVE: Dying patients often feel isolated and alone, and restricted visiting
      hours in the intensive care unit (ICU) has been shown to increase anxiety and
      dissatisfaction in both critically ill patients and their families. Unrestricted
      visiting has been identified as a top-ten need by families of patients in the
      ICU. Because emotional distress experienced by patients and families may persist
      well beyond the ICU stay, an open visiting policy, by meeting the needs of
      patients and families, may improve the quality of end-of-life care in the ICU.
      This two-part study included a survey to determine the visiting hours policies of
      New England-area hospital ICUs, and nursing focus groups to describe challenges
      and barriers that nursing staff working in an open ICU have experienced and to
      provide solutions that will facilitate implementation of an open visiting hours
      policy. DESIGN: Two-part study: survey and focus groups. SETTING: ICUs in New
      England and one medical ICU in a tertiary care hospital. SUBJECTS: Registered
      nurses employed in medical ICUs. INTERVENTIONS: Adult ICUs in the six New England
      states were located using a library listing of all regional hospitals. A
      telephone questionnaire interview was used to ascertain visiting hours policies
      in each ICU. Six focus-group sessions were conducted with nursing staff who work
      in an urban, northeastern ICU with 8 yrs of experience with an unrestricted
      visiting hours policy. MEASUREMENTS AND MAIN RESULTS: A total of 171 hospitals
      completed the questionnaire (96%). From all ICUs surveyed, 62 (32%) had
      unrestricted, open visiting hours. Out of these, 57 (92%) were medical ICUs or
      mixed medical/surgical ICUs. Nursing staff identified three major areas of
      concern with an open visiting hours policy: space, conflict, and burden.
      Strategies for resolution that are either employed or advocated by nursing staff
      are described. CONCLUSIONS: The majority of ICUs in New England have restricted
      visiting hours. Only one third of ICUs have open visiting policies. Nursing
      concerns with an unrestricted ICU were identified and solutions were offered that
      may provide guidance for other ICUs considering adopting an open visiting hours
      policy.

PMID- 17205013
TI  - Glucose-6-phosphate dehydrogenase deficiency and the inflammatory response to
      endotoxin and polymicrobial sepsis.
AB  - OBJECTIVE: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human
      genetic polymorphism. The deficiency protects against malaria but was shown to
      worsen the clinical course after severe trauma. This study tested whether the
      deficiency is associated with altered cytokine responses in vitro and in vivo and
      affects survival after endotoxemia or polymicrobial sepsis (cecal ligation and
      puncture). DESIGN: Genotyping of animals was carried out using a novel and
      improved allele-specific polymerase chain reaction assay. Macrophage and
      splenocyte responses in vitro and ex vivo were compared using gene array analyses
      and enzyme-linked immunosorbent assays and flow cytometry under both baseline and
      lipopolysaccharide-stimulated conditions. Endotoxemia- or sepsis-induced
      mortality was compared under a variety of treatment and resuscitation protocols.
      SETTINGS: Medical school research laboratories. SUBJECTS: Litter mates of wild
      type and G6PD-mutant mice that display a degree of G6PD deficiency similar to
      that observed in the African-type human deficiency (20% of normal). MEASUREMENTS
      AND MAIN RESULTS: Lipopolysaccharide in vivo (lipopolysaccharide from Escherichia
      coli, 10-35 mg/kg body weight intraperitoneally) resulted in greater interleukin
      1beta, interleukin-6, and interleukin-10 levels in serum and peritoneal lavage in
      G6PD-deficient mice compared with wild type. Prevailing doses of
      lipopolysaccharide in vivo increased mortality in G6PD-deficient animals (40-70%)
      as compared with wild type (5-40%). In contrast, mortality after cecal ligation
      and puncture-induced sepsis was similar in G6PD-deficient and wild-type animals
      either in saline-resuscitated or antibiotic-treated animals. Splenic and blood
      phagocytes from septic G6PD-deficient and wild-type animals displayed attenuated
      ex vivo lipopolysaccharide responsiveness. CONCLUSIONS: This study demonstrates
      that G6PD deficiency augments cytokine responses after inflammatory challenges.
      The deficiency is disadvantageous as reflected in increased mortality after
      hyperinflammation caused by acute endotoxemia. However, the deficiency may not
      manifest worsened survival after the immunosuppressed condition associated with
      severe sepsis.

PMID- 17205014
TI  - Effects of chronic sepsis on the voltage-gated sodium channel in isolated rat
      muscle fibers.
AB  - OBJECTIVE: Physiopathology of critical illness polyneuromyopathy was investigated
      in several animal-based models. Electrophysiologic approach was achieved in
      denervated and corticosteroid-induced myopathy; other models based on sepsis or
      inflammatory factors (zymosan, cytokines) were also used but did not consider
      voltage-gated sodium channel implication in neuromuscular weakness. We have
      studied electrophysiologic effects of chronic sepsis on an intact neuromuscular
      rat model with special consideration to the subtypes of sodium channels involved.
      DESIGN: Experimental animal study. SETTING: University laboratory. SUBJECTS:
      Wistar rats. INTERVENTIONS: Chronic sepsis was achieved by a technique of cecal
      ligature and needle perforation. Ten days after surgery, the rats were killed.
      Fast-twitch flexor digitorum brevis was excised and dissociated in 4-(2
      hydroxyethyl)-1-piperazineethanesulfonic acid-buffered saline supplemented with
      3.0 mg/mL collagenase. Fast sodium currents were recorded by a macropatch clamp
      technique at room temperature (22+/-2 degrees C) in a cell-attached
      configuration. MEASUREMENTS AND MAIN RESULTS: A decrease in maximal sodium
      current and in conductance was evidenced without modification of the sodium
      Nernst potential. A shift of the voltage inactivation curve toward more negative
      potentials could explain the observed decrease in excitability. In parallel, we
      observed an up-regulation of NaV 1.5-type sodium channels. CONCLUSIONS: Chronic
      inflammation and sepsis induced modifications of sodium channel properties that
      could contribute to muscular inexcitability. This inexcitability can be elicited
      by a modification of properties or type of voltage-gated sodium channels. Our
      results lead us to explain this inexcitability by an up-regulation of NaV 1.5
      sodium channel.

PMID- 17205015
TI  - Epidemiology of sedation and sedation adequacy for mechanically ventilated
      patients in a medical and surgical intensive care unit.
AB  - OBJECTIVE: Describe the pharmacoepidemiology of sedative medications and nurse
      rated patients' behavior and sedation adequacy. DESIGN: Cohort study, 2001-2003.
      PATIENTS: Patients ventilated for >36 hrs in a medical or surgical intensive care
      unit at a university-affiliated hospital. Proxies for 312 eligible subjects were
      approached for consent, 277 subjects enrolled, and data from 274 subjects were
      analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Distribution of
      Arousal and Motor Activity levels, proportion of inadequate sedation and factors
      associated with inadequate sedation, variation of sedative therapy intensity, and
      behavior over time were measured. Sedatives were administered in 85% of 18,050
      four-hour intervals during mechanical ventilation. Sedation was judged as
      adequate in 83% of 12,414 sedation assessments; patients were judged to be
      undersedated in 13.9% and oversedated in 2.6% of the assessments. Patients were
      unarousable or minimally arousable 32% of the time and had no spontaneous motor
      activity (during a 10-min observation period) 21.5% of the time. There was little
      variation in level of consciousness or motor activity or drug dose over 24 hrs,
      but daytime caregivers were more likely to judge patients as oversedated (3.7%)
      compared with nighttime caregivers (1.6%, p<.001). Inadequate sedation was
      associated with sedative drug intensity and patient behavior as measured by a two
      domain sedation scale. Sedative drug intensity and behavior varied during the
      course of respiratory failure, and survivors received 13% more sedation per 4-hr
      interval of mechanical ventilation than nonsurvivors (p<.001). CONCLUSIONS:
      Although patients were minimally arousable or nonarousable in 32% and motionless
      in 21% of the sedation assessments, surprisingly, an oversedation rating occurred
      in <3%. This discrepancy, along with findings that time of day influences the
      interpretation of sedation adequacy and that patients' behavior change over time
      suggests that collaborative research is needed to define adequate sedation.

PMID- 17205016
TI  - Hyperventilation following head injury: effect on ischemic burden and cerebral
      oxidative metabolism.
AB  - OBJECTIVE: To determine whether hyperventilation exacerbates cerebral ischemia
      and compromises oxygen metabolism (CMRO2) following closed head injury. DESIGN: A
      prospective interventional study. SETTING: A specialist neurocritical care unit.
      PATIENTS: Ten healthy volunteers and 30 patients within 10 days of closed head
      injury. INTERVENTIONS: Subjects underwent oxygen-15 positron emission tomography
      imaging of cerebral blood flow, cerebral blood volume, CMRO2, and oxygen
      extraction fraction. In patients, positron emission tomography studies,
      somatosensory evoked potentials, and jugular venous saturation (SjO2)
      measurements were obtained at Paco2 levels of 36+/-3 and 29+/-2 torr.
      MEASUREMENTS AND MAIN RESULTS: We estimated the volume of ischemic brain and
      examined the efficiency of coupling between oxygen delivery and utilization using
      the sd of the oxygen extraction fraction distribution. We correlated CMRO2 to
      cerebral electrophysiology and examined the effects of hyperventilation on the
      amplitude of the cortical somatosensory evoked potential response. Patients
      showed higher ischemic brain volume than controls (17+/-22 vs. 2+/-3 mL;
      p<or=.05), with worse matching of oxygen delivery to demand (p<.001).
      Hyperventilation consistently reduced cerebral blood flow (p<.001) and resulted
      in increases in oxygen extraction fraction and ischemic brain volume (17+/-22 vs.
      88+/-66 mL; p<.0001), which were undetected by SjO2 monitoring. Mean CMRO2 was
      slightly increased following hyperventilation, but responses were extremely
      variable, with 28% of patients demonstrating a decrease in CMRO2 that exceeded
      95% prediction intervals for zero change in one or more regions. CMRO2 correlated
      with cerebral electrophysiology, and cortical somatosensory evoked potential
      amplitudes were significantly increased by hyperventilation. CONCLUSIONS: The
      acute cerebral blood flow reduction and increase in CMRO2 secondary to
      hyperventilation represent physiologic challenges to the traumatized brain. These
      challenges exhaust physiologic reserves in a proportion of brain regions in many
      subjects and compromise oxidative metabolism. Such ischemia is underestimated by
      common bedside monitoring tools and may represent a significant mechanism of
      avoidable neuronal injury following head trauma.

PMID- 17205017
TI  - Loss of complexity characterizes the heart rate response to experimental
      hemorrhagic shock in swine.
AB  - OBJECTIVE: To improve our ability to identify physiologic deterioration caused by
      critical illness, we applied nonlinear and frequency-domain analytical methods to
      R-to-R interval (RRI) and systolic arterial pressure (SAP) time series during
      hemorrhagic shock. DESIGN: Prospective, randomized, controlled trial. SETTING:
      Animal laboratory of a government research institute. SUBJECTS: Twenty swine
      (weight 36.4+/-0.11 kg). INTERVENTIONS: Fixed-volume hemorrhage followed by
      resuscitation; off-line analysis of RRI and SAP data. MEASUREMENTS AND MAIN
      RESULTS: Anesthetized swine (shock group, n=12) underwent withdrawal of 30 mL/kg
      blood in 10 mL/kg decrements. A control group (n=8) received maintenance fluids
      only. Electrocardiogram and arterial pressure waveforms were acquired at 500 Hz.
      Eight hundred-beat data sets were analyzed at six time points: at baseline, after
      each blood withdrawal, after lactated Ringer's resuscitation, and after infusion
      of shed blood. Nonlinear methods were used to estimate the complexity
      (approximate entropy, sample entropy, Lempel-Ziv entropy, normalized entropy of
      symbol dynamics), RRI bits per word, and fractal dimension by curve lengths and
      by dispersion analysis of the RRI and SAP time series. Fast Fourier
      transformation was used to measure the high-frequency and low-frequency powers of
      RRI and SAP. Baroreflex sensitivity was assessed in the time domain with the
      sequence method. Hemorrhagic shock caused decreases in RRI complexity as
      quantified by approximate entropy, sample entropy, and symbol dynamics; these
      changes were reversed by resuscitation. Similar but statistically insignificant
      changes in fractal dimension by curve lengths were seen. RRI high-frequency power
      decreased with hemorrhagic shock-indicating withdrawal of vagal cardiac input-and
      was restored by resuscitation. Similar changes in baroreflex sensitivity were
      seen. Hemorrhagic shock did not affect SAP complexity. CONCLUSIONS: Hemorrhagic
      shock caused a reversible decrease in RRI complexity; these changes may be
      mediated by changes in vagal cardiac control. Assessment of RRI complexity may
      permit identification of casualties with hemorrhagic shock.

PMID- 17205018
TI  - N-acetylcysteine for patients with prolonged hypotension as prophylaxis for acute
      renal failure (NEPHRON).
AB  - BACKGROUND: Acute renal failure is a common complication in critically ill
      patients and carries an increased morbidity and mortality. N-acetylcysteine is an
      antioxidant and anti-inflammatory agent that may counteract some of the
      pathophysiologic derangements in shock states. OBJECTIVE: To test whether the
      administration of N-acetylcysteine, compared with placebo, reduces the incidence
      of acute renal failure in hypotensive patients. DESIGN: Prospective, randomized,
      double-blinded, placebo-controlled study. SETTING: Intensive care units of a
      university tertiary care hospital. PATIENTS: One hundred forty-two patients with
      new onset (within 12 hrs) of at least>or=30 consecutive minutes of hypotension
      and/or vasopressor requirement. INTERVENTIONS: Patients were randomized to
      receive either N-acetylcysteine or placebo for 7 days, in addition to standard
      supportive therapy. MEASUREMENTS AND MAIN RESULTS: Patients who received N
      acetylcysteine had an incidence of acute renal failure (>or=0.5 mg/dL increase in
      creatinine) of 15.5%, compared with 16.9% in those receiving placebo (p=.82, not
      significant). There were no significant differences between treatment arms in any
      of the secondary outcomes examined, including incidence of a 50% increase in
      creatinine, maximal rise in creatinine, recovery of renal function, length of
      intensive care unit and hospital stay, requirement for renal replacement therapy,
      and mortality. Among patients receiving N-acetylcysteine, there were trends
      toward reduced incidence of acute renal failure in patients with baseline
      Sequential Organ Failure Assessment (SOFA) score>8 (p=.12), lower SOFA scores
      during the first 4 days of treatment (p=.28), and reduced mortality in
      patients<65 yrs of age (p=.20). CONCLUSIONS: There were no significant
      differences in any of our primary or secondary end points between patients
      treated with N-acetylcysteine or placebo. Trends toward reduced incidence of
      acute renal failure in patients with baseline SOFA score >8, reduced SOFA scores
      during the first 4 days, and reduced mortality in patients<65 yrs of age are
      provocative but require further study to determine their clinical significance.

PMID- 17205019
TI  - Plasma gelsolin is a marker and therapeutic agent in animal sepsis.
AB  - OBJECTIVE: Plasma gelsolin is a circulating actin-binding protein that serves a
      protective role against tissue injuries. Depletion of plasma gelsolin in systemic
      inflammation may contribute to adverse outcomes. We examined the role of plasma
      gelsolin in animal models of sepsis. DESIGN: Animal and laboratory experiments.
      SETTING: Academic research laboratory. SUBJECTS: Adult male mice. INTERVENTIONS:
      Mice subjected to endotoxin or cecal ligation and puncture (CLP) were treated
      with exogenous plasma gelsolin or placebo. MEASUREMENTS AND MAIN RESULTS: We
      document the depletion of plasma gelsolin (25-50% of normal) in murine models of
      sepsis associated with the presence of circulating actin within 6 hrs of septic
      challenge. Repletion of plasma gelsolin leads to solubilization of circulating
      actin aggregates and significantly reduces mortality in endotoxemic mice
      (survival rates were 88% in the gelsolin group vs. 0% in the saline group, p <
      .001) and in CLP-challenged mice (survival rates were 30% in the gelsolin group
      vs. 0% in the saline group, p = .001). Plasma gelsolin repletion also shifted the
      cytokine profile of endotoxemic mice toward anti-inflammatory (plasma interleukin
      10 levels were 205 +/- 108 pg/mL in the gelsolin group vs. 39 +/- 29 pg/mL in the
      saline group, p = .02). CONCLUSIONS: We propose that circulation of particulate
      actin is a marker for sepsis-induced cell injury, that plasma gelsolin has a
      crucial protective role in sepsis, and that gelsolin replacement represents a
      potential therapy for this common lethal condition.

PMID- 17205020
TI  - Circadian rhythm of blood glucose values in critically ill patients.
AB  - OBJECTIVE: To test whether there is a circadian rhythm of blood glucose control
      in critically ill patients and whether morning blood glucose is an accurate
      surrogate of overall blood glucose control. DESIGN: Retrospective multiple-center
      observational study. SETTING: Intensive care units of three tertiary hospitals
      and one affiliated private hospital. PATIENTS: Cohort of 8,307 consecutive
      critically ill patients. INTERVENTIONS: Extraction of blood glucose values from
      electronically stored measurements. Extraction of demographic and outcome data
      from unit and hospital databases. Statistical assessment of variations in blood
      glucose control over each 24-hr cycle. MEASUREMENTS AND MAIN RESULTS: We studied
      208,362 blood glucose measurements in 8,307 patients (5.5
      measurements/day/person). In each hospital, there was a circadian rhythm of blood
      glucose control (p<.0001). The differences between highest and lowest blood
      glucose concentration in different time periods in each hospital were 0.27, 0.28,
      0.95, and 0.22 mmol/L. There was also significant variation in the incidence and
      notional duration of hyperglycemia. The differences between the lowest and
      highest incidence of hyperglycemia in different time periods were 3.3, 2.7, 9.9,
      and 2.6% in each hospital. In all four hospitals, the average blood glucose value
      from 5:30 am to 6:30 am was significantly lower than the 24-hr average.
      CONCLUSIONS: Blood glucose values and the incidence of hyperglycemia have a
      circadian rhythm in critically ill patients. Morning blood glucose may not be an
      accurate surrogate of blood glucose control over the daily cycle.

PMID- 17205021
TI  - Impact of a methicillin-resistant Staphylococcus aureus active surveillance
      program on contact precaution utilization in a surgical intensive care unit.
AB  - OBJECTIVE: To determine the impact of an active surveillance for methicillin
      resistant Staphylococcus aureus (MRSA) on contact precaution utilization, as
      measured by additional number of contact precaution days attributable to the
      active surveillance program. DESIGN: Prospective cohort study. SETTING: Twenty
      four-bed surgical intensive care unit (ICU). PATIENTS: All patients admitted to
      the surgical ICU. INTERVENTIONS: Nasal cultures for MRSA were performed at
      admission to a surgical ICU for 19 months. Patients admitted>48 hrs also received
      weekly and discharge nasal cultures. MEASUREMENTS AND MAIN RESULTS: Clinical
      data, including start date and initial indication for contact precautions, were
      prospectively collected. Of 1,893 admissions, 253 (13%) were found to be MRSA
      positive during their ICU stay. One hundred forty-six (58%) were identified by
      nasal culture alone. Compared with the first 10 months of study, the prevalence
      of MRSA on admission to the ICU during the last 9 months of the study period
      significantly increased (7.2% vs. 11.4%, p<.001). Acquisition of MRSA by
      noncolonized patients remained constant between the first 10 months and last 9
      months of study (7.0 vs. 5.5 cases per 1000 patient days, p=.29). Two hundred
      fourteen (6%) of 3461 total contact precaution days in the ICU were attributable
      to MRSA active surveillance. In sensitivity analyses, the implementation of
      rapid, same-day results for MRSA active surveillance would increase contact
      precaution days by 15% compared with no surveillance. If the total number of
      vancomycin-resistant enterococci patients in the ICU were reduced by 50%, the
      contact precaution days attributable to active surveillance would increase to 9%.
      CONCLUSIONS: MRSA active surveillance increased total contact precaution days in
      this ICU by 6% yet detected 58% of MRSA cases that would have been otherwise
      missed. Despite an increasing prevalence of MRSA on admission to the ICU, the
      acquisition rate has remained constant.

PMID- 17205022
TI  - Blood transfusions are associated with increased risk for development of sepsis
      in severely burned pediatric patients.
AB  - OBJECTIVE: To determine the risk of developing sepsis following transfusion of
      blood products in severely burned pediatric patients. DESIGN: Retrospective,
      cohort study. SETTING: Shriners Hospital for Children and University Hospital.
      PATIENTS: Severely burned pediatric patients with >30% total body surface area
      (TBSA) burn. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred
      seventy-seven pediatric burn patients over a period of 7 yrs (1997-2004) were
      included in the study, with 25 patients being septic at admission and therefore
      excluded. Patients were stratified according to TBSA burn and presence or absence
      of inhalation injury. The amounts of packed red blood cells (RBCs) and fresh
      frozen plasma (FFP) were recorded during hospital stay before the development of
      sepsis. Blood product administration was normalized for the number of surgeries
      and divided into two groups: high (RBCs>20/FFP>5) or low (RBCs<20/FFP<5) amount
      of blood products. Sepsis was diagnosed based on the criteria set by the Society
      of Critical Care Medicine in conjunction with positive blood culture or presence
      of organisms in the organs at autopsy. By stratifying the groups into low and
      high blood transfusion, we found that patients with >60% TBSA burn with
      inhalation injury have an 8% risk of developing sepsis in the low RBC group,
      which increases to 58% in the high RBC group (p<.05). Similar results were found
      for RBCs per operation, FFP, and FFP per operation (p<.05). There were no
      differences in age and gender between groups. CONCLUSIONS: Pediatric burn
      suffering from a 60% TBSA burn with concomitant inhalation injury are more likely
      to develop sepsis if they are given high amounts of blood products, indicating an
      immunocompromised state following blood transfusion.

PMID- 17205023
TI  - Immunomodulation by n-3- versus n-6-rich lipid emulsions in murine acute lung
      injury--role of platelet-activating factor receptor.
AB  - OBJECTIVE: Cytokines, platelet-activating factor (PAF), and eicosanoids control
      local and systemic inflammation. Conventional soybean oil-based lipid emulsions
      used for parenteral nutrition may aggravate the leukocyte inflammatory response
      or adhesion to the vessel wall. Fish oil-based lipid emulsions, in contrast, may
      exert an anti-inflammatory effect. DESIGN: We investigated the impact of lipid
      emulsions on leukocyte invasion, protein leakage, and cytokines in two murine
      models of acute inflammation. SETTING: Research laboratory of a university
      hospital. SUBJECTS: Wild-type mice and PAF-receptor knockout mice. INTERVENTIONS:
      Mice received an infusion of normal saline, fish oil- or soybean oil-based lipid
      emulsions before lipopolysaccharide challenge. MEASUREMENTS AND MAIN RESULTS:
      Preinfusion with soybean oil resulted in increased leukocyte invasion,
      myeloperoxidase activity, and protein leakage and exaggerated release of tumor
      necrosis factor (TNF)-alpha as well as macrophage inflammatory protein (MIP)-2
      into the alveolar space after intratracheal lipopolysaccharide challenge. In
      contrast, preinfusion with fish oil reduced leukocyte invasion, myeloperoxidase
      activity, protein leakage, and TNF-alpha as well as MIP-2 generation.
      Corresponding profiles were found in plasma following intraperitoneal
      lipopolysaccharide application: Soybean oil increased but fish oil decreased the
      TNF-alpha and MIP-2 formation. When PAF-receptor-deficient mice were challenged
      with lipopolysaccharide, leukocyte invasion, lung tissue myeloperoxidase,
      cytokine generation, and alveolar protein leakage corresponded to those observed
      in wild-type animals. Fish oil and soybean oil lost their diverging effects on
      leukocyte transmigration, myeloperoxidase activity, leakage response, and
      cytokine generation in these knockout mice. Similarly, the differential impact of
      both lipid emulsions on these lipopolysaccharide-provoked changes was suppressed
      after pretreating animals with a PAF-receptor antagonist. CONCLUSIONS: Fish oil-
      vs. soybean oil-based lipid infusions exert anti- vs. proinflammatory effects in
      murine models of acute inflammation. The PAF/PAF-receptor-linked signaling
      appears to be a prerequisite for this differential profile.

PMID- 17205024
TI  - Longitudinal studies of inter-alpha inhibitor proteins in severely septic
      patients: a potential clinical marker and mediator of severe sepsis.
AB  - OBJECTIVE: To determine the clinical relevance and prognostic significance of
      serial measurement of inter-alpha inhibitor proteins (IalphaIp) in severely
      septic patients. DESIGN: A laboratory-based study of serial plasma samples over
      the first 5 days of severe sepsis from a prospective clinical trial. SETTING:
      Small business and academic medical center research laboratories. PATIENTS: Two
      hundred sixty-six patients with severe sepsis from a multiple-center phase III
      clinical trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Inter-alpha
      inhibitor proteins serve as endogenous serine protease inhibitors in human
      plasma. The levels of IalphaIp were markedly reduced to a mean value of 290+/-15
      microg/mL at the onset of severe sepsis compared with normal plasma levels (617+/
      197 microg/mL). Failure of IalphaIp levels to recover over the first 5 days of
      sepsis was associated with an unfavorable outcome (p<.001). IalphaIp levels were
      inversely correlated with interleukin-6 levels at study entry and over the first
      5 days of management of severe sepsis. IalphaIp levels were significantly lower
      in women, with increased age, in the presence of multiple organ failure and in
      patients with intra-abdominal sources of sepsis. CONCLUSIONS: Inter-alpha
      inhibitor proteins are markedly reduced in severe sepsis, and failure of recovery
      of IalphaIp levels over the course of sepsis is associated with an unfavorable
      outcome.

PMID- 17205025
TI  - Variables associated with positive findings at relaparotomy in patients with
      secondary peritonitis.
AB  - OBJECTIVE: The decision whether and when to perform a relaparotomy in secondary
      peritonitis is largely subjective and based on professional experience. No
      existing scoring system aids in this decisional process. Our aim was to search
      for variables that could predict positive findings at relaparotomy. DESIGN:
      Retrospective, clinical study. SETTING: Tertiary university hospital. PATIENTS:
      Two hundred and nineteen patients of a consecutive series who underwent an
      emergency laparotomy for secondary peritonitis. INTERVENTIONS: None. Sequential
      prediction models were constructed by accumulation of clinical information in
      chronological order using logistic regression to determine the strength of
      association between predictive variables and positive findings at relaparotomy
      outcome. Positive findings were defined as persistent peritonitis or a new
      infectious focus at relaparotomy. MEASUREMENTS AND MAIN RESULTS: Relaparotomy
      (planned or on demand) for secondary peritonitis was performed in 117 of 219
      patients (53%), yielding either positive (n=62) or negative (n=55) findings.
      Discriminatory power for positive findings at relaparotomy improved in the
      successive (multivariate) models: general patient characteristics (area under the
      curve, 0.60; 95% confidence interval, 0.52-0.68), adding peritonitis-related
      variables (area under the curve, 0.73; 95% confidence interval, 0.66-0.80),
      adding operation-related variables (area under the curve, 0.74; 95% confidence
      interval, 0.67-0.81), and adding postoperative variables (area under the curve,
      0.87; 95% confidence interval, 0.82-0.92). Bootstrap resampling reduced the areas
      under the curve of the subsequent models only slightly. Sensitivity and
      specificity of the final model were 82% and 76%, respectively, at a total error
      rate of 16%. One preoperative predictor and five postoperative predictors
      significantly increased the need for relaparotomy: younger age, decreased
      hemoglobin levels, temperature>39 degrees C, lower Pao2/Fio2 ratio, increased
      heart rate, and increased sodium levels. CONCLUSIONS: These data suggest that the
      causes of secondary peritonitis and findings at emergency laparotomy for
      peritonitis are poor indicators for whether patients will need a relaparotomy.
      Factors indicative of progressive or persistent organ failure during early
      postoperative follow-up are the best indicators for ongoing infection and
      associated positive findings at relaparotomy.

PMID- 17205026
TI  - Perflubron dosing affects ventilator-induced lung injury in rats with previous
      lung injury.
AB  - OBJECTIVES: Randomized controlled trials of partial liquid ventilation in acute
      respiratory distress syndrome have been negative. Reasons for this failure may
      reside in the use of too large doses of perfluorocarbon. The objective was to
      evaluate whether various doses of perflubron affect ventilation-induced injury in
      edematous lungs in different ways. DESIGN: Prospective, controlled animal study.
      SETTING: Research laboratory of a university. SUBJECTS: Male Wistar rats weighing
      300+/-20 g. INTERVENTIONS: Separate groups of rats were injected with alpha
      naphtylthiourea to produce mild permeability pulmonary edema. They were then
      given 0, 7 (low), 13 (moderate), or 20 mL/kg (near functional residual capacity)
      perflubron doses and mechanically ventilated with a large (33 mL/kg) tidal volume
      for 15 mins. MEASUREMENTS AND MAIN RESULTS: 125I-albumin distribution space was
      used to assess lung microvascular permeability. Quasi-static respiratory system
      pressure-volume curves were analyzed. Administration of low and moderate
      perflubron doses significantly improved respiratory mechanics and reduced the
      ventilator-induced permeability alterations to the level observed in rats that
      were not ventilated. By contrast, a perflubron dose that was near functional
      residual capacity increased end-inspiratory plateau pressure and aggravated the
      permeability alterations due to high tidal volume ventilation. CONCLUSIONS: Near
      functional residual capacity but not low perflubron dose worsens ventilation
      induced lung injury of preinjured lungs. This may provide some explanation for
      the negative results of the recent clinical trials, and it stresses the
      importance of the amount of perflubron used for partial liquid ventilation.

PMID- 17205027
TI  - Acute effects of hyperglycemia and hyperinsulinemia on hepatic oxidative stress
      and the systemic inflammatory response in rats.
AB  - OBJECTIVES: Intensive blood glucose control to a target value of 80-110 mg/dL has
      been shown to reduce morbidity and mortality in surgical intensive care unit
      patients. This was attributed predominantly to correction of hyperglycemia, based
      on multivariate regression analysis. However, the effects of glucose and insulin
      have not been independently evaluated. This study investigated the development of
      hepatic oxidative processes and systemic inflammatory response in rats with
      different levels of induced hyperglycemia and hyperinsulinemia. The effects of a
      modest increase in blood glucose following glucose infusion at a level adequate
      to meet energy requirements, hyperinsulinemia induced by a hyperinsulinemic
      euglycemic clamp with administered glucose in similar amounts, and marked
      hyperglycemia and hyperinsulinemia secondary to glucose infusion on hepatic
      oxidative stress and systemic inflammatory response in vivo were examined.
      DESIGN: Controlled laboratory study. SETTING: Medical school laboratory.
      SUBJECTS: Specific pathogen-free male Sprague-Dawley rats. INTERVENTIONS: Blood
      glucose was monitored over 3 hrs. At the end of study, the serum concentrations
      of insulin, tumor necrosis factor-alpha, interleukin-1, and alpha1 acid
      glycoprotein were determined. Malondialdehyde and total glutathione content were
      measured in the liver. MEASUREMENTS AND MAIN RESULTS: Glucose infusion adequate
      to provide energy requirements resulted in a modest increase in blood glucose
      (143+/-8 mg/dL) and hyperinsulinemia (45 microU/mL) and did not induce measurable
      hepatic oxidative stress or systemic inflammation. A hyperinsulinemic euglycemic
      clamp (insulin 112+/-9 microU/mL) resulted in evidence of increased oxidative
      processes in the liver but no change in hepatic antioxidant capacity or evidence
      of systemic inflammation. When hyperglycemia (approximately 350 mg/dL) and
      hyperinsulinemia (167+/-9 microU/mL) were induced by excess glucose infusion,
      rats manifested hepatic oxidative stress, antioxidant depletion, and a mild
      systemic inflammatory response. CONCLUSIONS: Hyperglycemia is a major cause of
      the systemic inflammatory response. Maintaining normal blood glucose, by avoiding
      overfeeding and providing insulin therapy when necessary, appears key to
      minimizing oxidative stress and systemic inflammation when intravenous nutrition
      is provided.

PMID- 17205028
TI  - Topical chlorhexidine for prevention of ventilator-associated pneumonia: a meta
      analysis.
AB  - OBJECTIVE: To assess the efficacy of topical chlorhexidine for prevention of
      ventilator-associated pneumonia (VAP) in a meta-analysis. DATA SOURCE:
      Computerized PubMed and MEDLINE search supplemented by manual searches for
      relevant articles. STUDY SELECTION: Randomized controlled trials evaluating
      efficacy of topical chlorhexidine applied to the oropharynx vs. placebo or
      standard care for prevention of VAP. DATA EXTRACTION: Data were extracted on
      patient population, inclusion and exclusion criteria, diagnostic criteria for
      VAP, form and concentration of topical chlorhexidine used, incidence of VAP, and
      overall mortality. DATA SYNTHESIS: Data on incidence of VAP and mortality were
      abstracted as dichotomous variables. Pooled estimates of the relative risk and
      95% confidence intervals were obtained using the DerSimonian and Laird random
      effects model and the Mantel-Haenszel fixed effects model. Heterogeneity was
      assessed using the Cochran Q statistic and I. Subgroup analyses were used to
      explore heterogeneity. RESULTS: Seven randomized controlled trials met the
      inclusion criteria. Topical chlorhexidine resulted in a reduced incidence of VAP
      (relative risk, 0.74; 95% confidence interval, 0.56-0.96; p=.02) using a fixed
      effects model. Using the more conservative random effects model, the point
      estimate was similar (relative risk, 0.70; 95% confidence interval, 0.47-1.04;
      p=.07), but the results failed to achieve statistical significance. The I test
      showed moderate heterogeneity. Subgroup analysis showed that the benefit of
      chlorhexidine was most marked in cardiac surgery patients (relative risk, 0.41;
      95% confidence interval, 0.17-0.98; p=.04). There was no mortality benefit with
      chlorhexidine although the sample size was small. CONCLUSIONS: Our analysis
      showed that topical chlorhexidine is beneficial in preventing VAP; the benefit is
      most marked in cardiac surgery patients. A large randomized trial is needed to
      determine the impact of topical chlorhexidine on mortality.

PMID- 17205029
TI  - The quality of reports of critical care meta-analyses in the Cochrane Database of
      Systematic Reviews: an independent appraisal.
AB  - OBJECTIVE: To independently appraise the methodological quality of a sample of
      reports of meta-analyses that address critical care topics in the Cochrane
      Database of Systematic Reviews compared with the quality of reports published in
      regular journals, using a validated assessment instrument, the Overview Quality
      Assessment Questionnaire (OQAQ). DATA SOURCE: Studies were selected from a search
      of MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 1994 to
      2003, using multiple search terms for critical care and sensitive filters to
      identify meta-analyses. STUDY SELECTION: Two authors independently selected meta
      analyses that addressed topics pertinent to critical care medicine. DATA
      EXTRACTION: Two authors independently extracted the data. The proportion of
      reports that met each component of the OQAQ was determined, as was the overall
      quality score. Meta-analyses published in the Cochrane Database of Systematic
      Reviews were compared with those published in regular journals. DATA SYNTHESIS:
      There were 36 reports of meta-analyses in the Cochrane Database of Systematic
      Reviews and 103 reports of meta-analyses published in regular journals; 11 of
      these were reports of Cochrane reviews. The meta-analyses published in the
      Cochrane Database of Systematic Reviews were more likely to fulfill most
      components of the OQAQ. The median overall OQAQ scores indicated significant
      methodological problems in the reports regardless of the source of publication,
      although the reports in the Cochrane database scored higher than those in regular
      journals (five compared with two, p<.001). Major methodological flaws, notably
      failure to appropriately refer to the validity of included studies, were found in
      meta-analyses in both the Cochrane Database of Systematic Reviews and regular
      journals (44.4% and 79.3%, respectively). CONCLUSIONS: Although the quality of
      reports of meta-analyses published in the Cochrane Database of Systematic Reviews
      is superior to the quality of reports of meta-analyses published in regular
      journals, there is significant room for improvement. Clinicians should critically
      appraise all reports of meta-analyses before considering the results, regardless
      of the source of publication.

PMID- 17205030
TI  - Osmotherapy with hypertonic saline attenuates water content in brain and
      extracerebral organs.
AB  - OBJECTIVE: Because of their beneficial effects in patients with hemorrhagic shock
      and multiple-system trauma, hypertonic saline solutions are increasingly being
      used perioperatively for volume resuscitation. Although the anti-edema effects of
      hypertonic saline on brain are well documented in a variety of brain injury
      paradigms, its effects on the water content on other organs has not been studied
      rigorously. In this study, we tested the hypothesis that a) hypertonic saline
      when given as an intravenous bolus and continuous infusion attenuates water
      content of small bowel, lung, and brain in rats without neuro-injury; and b)
      attenuation of stroke-associated increases in lung water is dependent on
      achieving a target serum osmolality. DESIGN: Prospective laboratory animal study.
      SETTING: Research laboratory in a teaching hospital. SUBJECTS: Adult male Wistar
      rats. INTERVENTIONS: In the first series of experiments, under controlled
      conditions of normoxia, normocarbia, and normothermia, spontaneously breathing,
      halothane-anesthetized (1.0-1.5%) adult male Wistar rats (280-320 g) were treated
      in a blinded randomized fashion with 7.5% hypertonic saline or 0.9% normal saline
      in a 8-mL/kg intravenous infusion for 3 hrs followed by a continuous intravenous
      infusion (1 mL/kg/hr) of 5% hypertonic saline or normal saline, respectively
      (n=10 each), for 48 hrs. A second group of rats were treated with continuous
      infusion only for 48 hrs of either 7.5% hypertonic saline or normal saline (1
      mL/kg/hr) (n=10 each) without an intravenous bolus. Naive rats served as controls
      (n=10). Tissue water content of small bowel, lung, and brain was determined by
      comparing the wet-to-dry ratios at the end of the experiment. In a second series
      of experiments, rats (n=94) were subjected to 2 hrs of transient middle cerebral
      artery occlusion by the intraluminal occlusion technique. At 6 hrs following
      middle cerebral artery occlusion, rats were treated in a blinded randomized
      fashion with a continuous intravenous infusion of normal saline, 3% hypertonic
      saline, or 7.5% hypertonic saline for 24, 48, 72, and 96 hrs. Surgical shams
      served as controls (n=7). Hypertonic saline was instituted as chloride/acetate
      mixture (50:50) in all experiments. Serum osmolality was determined at the end of
      the experiment in all animals. MEASUREMENTS AND MAIN RESULTS: In rats without
      neuro-injury that received intravenous bolus followed by a continuous infusion,
      lung water content was significantly reduced with hypertonic saline (73.9+/-1.1%;
      359+/-10 mOsm/L) (mean+/-sd) compared with normal saline treatment (76.1+/-0.53%;
      298+/-4 mOsm/L) as was water content of small bowel (hypertonic saline, 69.1+/
      5.8%; normal saline, 74.7+/-0.71%) and brain (hypertonic saline, 78.1+/-0.87%;
      normal saline, 79.2+/-0.38%) at 48 hrs. Stroke-associated increases in lung water
      content were attenuated with 7.5% hypertonic saline at all time points. There was
      a strong correlation between serum osmolality and attenuation of stroke
      associated increases in lung water content (r=-.647) CONCLUSIONS: Bowel, lung,
      and brain water content is attenuated with hypertonic saline when serum
      osmolality is >350 mOsm/L without adverse effect on mortality in animals with and
      without neuro-injury. Attenuation of water content of extracerebral organs with
      hypertonic saline treatment may have therapeutic implications in perioperative
      fluid management in patients with and without brain injury.

PMID- 17205031
TI  - Clinical and hemostatic responses to treatment in ventilator-associated
      pneumonia: role of bacterial pathogens.
AB  - OBJECTIVE: To determine pathogen-specific kinetic changes in the alveolar
      procoagulant (PC) activity, tissue factor (TF), and tissue factor pathway
      inhibitor (TFPI) expression during the course of ventilator-associated pneumonia
      (VAP) and to assess the relationship between clinical resolution, intra-alveolar
      bacterial eradication, and restoration of hemostatic balance. DESIGN:
      Prospective, multiple-center study in a cohort of VAP patients. SETTING: Two
      university-affiliated intensive care units. PATIENTS: Thirty-five patients with
      microbiologically documented VAP who received adequate antimicrobial coverage and
      13 controls. INTERVENTIONS: Nonbronchoscopic bronchoalveolar lavage was performed
      at the onset of VAP and on days 4 and 8 after initiation of antibiotic therapy.
      Samples were assayed for PC, TF, TFPI, and thrombin-antithrombin complex (TATc).
      The corresponding Clinical Pulmonary Infection Score (CPIS) was collected
      simultaneously. MEASUREMENTS AND MAIN RESULTS: Isolated pathogens included
      Pseudomonas aeruginosa (n=13), methicillin-resistant Staphylococcus aureus (MRSA)
      (n=8), methicillin-sensitive S. aureus (MSSA) (n=7), and Escherichia coli (n=7).
      Although PC activity and TF were increased among the various pathogens at the
      onset of VAP, the levels of those with P. aeruginosa remained elevated at the end
      of treatment compared with controls and other etiological agents. TFPI levels
      were elevated for the duration of the study for all pathogens. A universal
      increase in TATc was noted at the onset of VAP, but the difference among the
      group of pathogens was significant at days 4 and 8 posttherapy. Despite the
      persisting hemostatic imbalance and incomplete intra-alveolar eradication of P.
      aeruginosa at end of therapy, the CPIS fell comparably at each time point
      irrespective of the etiological agents. CONCLUSIONS: Alveolar activation of the
      TF-dependent pathway may be species-specific in VAP and may not be adequately
      balanced by TFPI. The disparity between clinical response and eradication of P.
      aeruginosa from the intra-alveolar space suggests the need for biological markers
      to guide response to therapy.

PMID- 17205032
TI  - Erythromycin is more effective than metoclopramide in the treatment of feed
      intolerance in critical illness.
AB  - OBJECTIVE: This study aimed to a) compare the efficacy of metoclopramide and
      erythromycin in the treatment of feed intolerance in critical illness; and b)
      determine the effectiveness of "rescue" combination therapy in patients who fail
      monotherapy. DESIGN: Randomized controlled trial. SETTING: Level III mixed
      medical and surgical intensive care unit. PATIENTS: Ninety mechanically
      ventilated, medical patients with feed-intolerance (gastric residual
      volume>or=250 mL). INTERVENTIONS: Patients received either metoclopramide 10 mg
      intravenously four times daily (n=45) or erythromycin 200 mg intravenously twice
      a day (n=45) in a double-blind, randomized fashion. After the first dose,
      nasogastric feeding was commenced and 6-hourly nasogastric aspirates were
      performed. If a gastric residual volume>or=250 mL recurred on treatment, open
      label, combination therapy was given. Patients were studied for 7 days.
      Successful feeding was defined as 6-hourly gastric residual volume<250 mL with a
      feeding rate>or=40 mL/hr. MEASUREMENTS AND MAIN RESULTS: Demographic data, blood
      glucose levels, and use of inotropes, opioids, and benzodiazepines were similar
      between the two groups. After 24 hrs of treatment, both monotherapies reduced the
      mean gastric residual volume (metoclopramide, 830+/-32 mL to 435+/-30 mL,
      p<.0001; erythromycin, 798+/-33 mL to 201+/-19 mL, p<.0001) and improved the
      proportion of patients with successful feeding (metoclopramide=62% and
      erythromycin=87%). Treatment with erythromycin was more effective than
      metoclopramide, but the effectiveness of both treatments declined rapidly over
      time. In patients who failed monotherapy, rescue combination therapy was highly
      effective (day 1=92%) and maintained its effectiveness for the study duration
      (day 6=67%). High pretreatment gastric residual volume was associated with poor
      response to prokinetic therapy. CONCLUSIONS: In critical illness, erythromycin is
      more effective than metoclopramide in treating feed intolerance, but the rapid
      decline in effectiveness renders both treatments suboptimal. Rescue combination
      therapy is highly effective, and further study is required to examine its role as
      the first-line therapy.

PMID- 17205033
TI  - Folate status in women of childbearing age, by race/ethnicity--United States,
      1999-2000, 2001-2002, and 2003-2004.
AB  - Fortification of enriched cereal-grain products with folic acid to help prevent
      pregnancies affected by a neural tube defect (NTD) (e.g., spina bifida or
      anencephaly) became mandatory in the United States in January 1998. Data from the
      1999-2000 National Health and Nutrition Examination Survey (NHANES) indicated
      that median serum folate concentrations in nonpregnant women of childbearing age
      had increased substantially, compared with concentrations during a period (1988
      1994) before fortification was mandated. This report uses NHANES data to update
      those findings and assess trends in serum folate and red blood cell (RBC) folate
      levels by race/ethnicity from the 1999--2000 survey through the 2003-2004 survey.
      The results of these comparisons indicated that median serum folate
      concentrations among nonpregnant women of childbearing age decreased 16% from
      1999-2000 through 2003-2004, and RBC folate concentrations decreased 8%. All
      women of childbearing age who are capable of becoming pregnant should consume 400
      microg of folic acid daily to reduce the occurrence of NTD-affected pregnancies.

PMID- 17205034
TI  - Latent tuberculosis infection among sailors and civilians aboard U.S.S. Ronald
      Reagan--United States, January-July 2006.
AB  - Crews aboard ships live and work in crowded, enclosed spaces. Historically, large
      tuberculosis (TB) outbreaks and extensive transmission of Mycobacterium
      tuberculosis have occurred on U.S. Navy ships. On July 13, 2006, smear- and
      culture-positive, cavitary, pulmonary TB was diagnosed in a sailor aboard the
      aircraft carrier U.S.S. Ronald Reagan; the patient, aged 32 years, had a negative
      human immunodeficiency virus test. The M. tuberculosis strain cultured was
      susceptible to all first-line TB medications. The sailor was born in the
      Philippines, had latent tuberculosis infection (LTBI) diagnosed in 1995 shortly
      after enlisting in the U.S. Navy, and completed the 6-month daily isoniazid
      course that was standard treatment at that time (current treatment standard is 9
      months). This report describes the contact investigation conducted by the U.S.
      Navy and CDC and demonstrates the importance of timely diagnosis of TB,
      identification and treatment of new LTBI, and cooperation among local, state, and
      federal agencies during large contact investigations.

PMID- 17205035
TI  - S5 Lipase: an organic solvent tolerant enzyme.
AB  - In this study, an organic solvent tolerant bacterial strain was isolated. This
      strain was identified as Pseudomonas sp. strain S5, and was shown to degrade BTEX
      (Benzene, Toluene, Ethyl-Benzene, and Xylene). Strain S5 generates an organic
      solvent-tolerant lipase in the late logarithmic phase of growth. Maximum lipase
      production was exhibited when peptone was utilized as the sole nitrogen source.
      Addition of any of the selected carbon sources to the medium resulted in a
      significant reduction of enzyme production. Lower lipase generation was noted
      when an inorganic nitrogen source was used as the sole nitrogen source. This
      bacterium hydrolyzed all tested triglycerides and the highest levels of
      production were observed when olive oil was used as a natural triglyceride. Basal
      medium containing Tween 60 enhanced lipase production to the most significant
      degree. The absence of magnesium ions (Mg2+) in the basal medium was also shown
      to stimulate lipase production. Meanwhile, an alkaline earth metal ion, Na+, was
      found to stimulate the production of S5 lipase.

PMID- 17205036
TI  - Evaluation of the diversity of cyclodextrin-producing Paenibacillus graminis
      strains isolated from roots and rhizospheres of different plants by molecular
      methods.
AB  - To address the diversity of cyclodextrin-producing P. graminis strains isolated
      from wheat roots and rhizospheres of maize and sorghum sown in Australia, Brazil,
      and France, restriction fragment length polymorphism analysis of part of genes
      encoding RNA polymerase (rpoB-RFLP) and DNA gyrase subunit B (gyrB-RFLP) was used
      to produce genetic fingerprints. A phylogenetic tree based on rpoB gene sequences
      was also constructed. The isolates originated from Brazil could be separated from
      those from Australia and France, when data from the rpoB-based phylogenetic tree
      or gyrB-RFLP were considered. These analyses also allowed the separation of all
      P. graminis strains studied here into four clusters; one group formed by the
      strains GJK201 and RSA19T, second group formed by the strains MC22.02 and
      MC04.21, third group formed by the strains TOD61, TOD 221, TOD302, and TOD111,
      and forth group formed by all strains isolated from plants sown in Cerrado soil,
      Brazil. As this last group was formed by strains isolated from sorghum and maize
      sown in the same soil (Cerrado) in Brazil, our results suggest that the diversity
      of these P. graminis strains is more affected by the soil type than the plant
      from where they have been isolated.

PMID- 17205037
TI  - Phylogenetic diversity of acidophilic sporoactinobacteria isolated from various
      soils.
AB  - Spore forming actinobacteria (sporoactinobacteria) isolated from soils with an
      acidic pH in Pinus thunbergii forests and coal mine waste were subjected to
      taxonomic characterization. For the isolation of acidophilic actinobacteria,
      acidified starch casein agar (pH adjusted to 4-5) was used. The numbers of
      actinobacteria growing in acidic media were between 3.2 x 10(4) and 8.0 x 10(6)
      CFU/g soil. Forty three acidophilic actinobacterial strains were isolated and
      their 16S rDNA sequences were determined. The isolates were divided into eight
      distinctive phylogenetic clusters within the variation encompassed by the family
      Streptomycetaceae. Four clusters among them were assigned to the genus
      Streptacidiphilus, whereas the remaining four were assigned to Streptomyces. The
      clusters belonging to either Streptomyces or Streptacidiphilus did not form
      monophyletic clade. The growth pH profiles indicated that the representative
      isolates grew best between pH 5 and 6. It is evident from this study that acidity
      has played a critical role in the differentiation of the family
      Streptomycetaceae, and also that different mechanisms might have resulted in the
      evolution of two groups, Streptacidiphilus (strict acidophiles) and
      neutrotolerant acidophilic Streptomyces. The effect of geographic separation was
      clearly seen among the Streptacidiphilus isolates, which may be a key factor in
      speciation of the genus.

PMID- 17205038
TI  - Molecular characterization of marine Cyanobacteria from the Indian subcontinent
      deduced from sequence analysis of the phycocyanin operon (cpcb-IGS-cpcA) and 16S
      23S ITS region.
AB  - Molecular characterization of ten marine cyanobacterial isolates belonging to the
      order Oscillatoriales was carried out using the phycocyanin locus (cpcBA-IGS) and
      the 16S-23S internally transcribed spacer region. DNA sequences from the
      phycocyanin operon discriminated ten genotypes, which corresponded to seven
      morphotypes identified by traditional microscopic analysis. The cpcB coding
      region revealed 17 % nucleotide variation, while cpcA exhibited 29 % variation
      across the studied species. Phylogenetic analyses support the conclusion that the
      Phormidium and Leptolyngbya genera are not monophyletic. The nucleotide
      variations were heterogeneously distributed with no or minimal informative
      nucleotides. Our results suggest that the discriminatory power of the phycocyanin
      region varies across the cyanobacterial species and strains. The DNA sequence
      analysis of the 16S-23S internally transcribed spacer region also supports the
      polyphyletic nature of the studied oscillatorian cyanobacteria. This study
      demonstrated that morphologically very similar strains might differ
      genotypically. Thus, molecular approaches comprising different gene regions in
      combination with morphological criteria may provide better taxonomical resolution
      of the order Oscillatoriales.

PMID- 17205039
TI  - Increase of yeast survival under oxidative stress by the expression of the
      laccase gene from Coprinellus congregatus.
AB  - Coprinellus congregatus secreted a laccase isozyme when the culture was
      transferred to an acidic liquid medium (pH 4.1). The laccase cDNA gene (clac2)
      was used as a probe for cloning of the genomic laccase gene (lac2) including the
      promoter (Plac2). The open reading frame (ORF) of lac2 had 526 deduced amino
      acids and four conserved copper binding domains as other fungal laccases.
      Recombinant plasmid (pRSlac2p-cDNA) of lac2 cDNA with its own promoter was
      transformed in Saccharomyces cerevisiae. Expression of the transformed lac2 gene
      was induced by oxidative stress (H2O2) in yeast and the survival rate of the
      transformed yeast strain was greatly increased when compared with that of the
      control strain transformed with pRS316 yeast vector.

PMID- 17205040
TI  - A fibrinolytic enzyme from the medicinal mushroom Cordyceps militaris.
AB  - In this study we purified a fibrinolytic enzyme from Cordyceps militaris using a
      combination of ion-exchange chromatography on a DEAE Sephadex A-50 column, gel
      filtration chromatography on a Sephadex G-75 column, and FPLC on a HiLoad 16/60
      Superdex 75 column. This purification protocol resulted in a 191.8-fold
      purification of the enzyme and a final yield of 12.9 %. The molecular mass of the
      purified enzyme was estimated to be 52 kDa by SDS-PAGE, fibrin-zymography, and
      gel filtration chromatography. The first 19 amino acid residues of the N-terminal
      sequence were ALTTQSNV THGLATISLRQ, which is similar to the subtilisin-like
      serine protease PR1J from Metarhizium anisopliae var. anisopliase. This enzyme is
      a neutral protease with an optimal reaction pH and temperature of 7.4 and 37
      degrees , respectively. Results for the fibrinolysis pattern showed that the
      enzyme rapidly hydrolyzed the fibrin alpha-chain followed by the gamma-gamma
      chains. It also hydrolyzed the beta-chain, but more slowly. The Aalpha, Bbeta,
      and gamma chains of fibrinogen were also cleaved very rapidly. We found that
      enzyme activity was inhibited by Cu2+ and Co2+, but enhanced by the additions of
      Ca2+ and Mg2+ ions. Furthermore, fibrinolytic enzyme activity was potently
      inhibited by PMSF and APMSF. This enzyme exhibited a high specificity for the
      chymotrypsin substrate S-2586 indicating it 's a chymotrypsin-like serine
      protease. The data we present suggest that the fibrinolytic enzyme derived from
      the edible and medicinal mushroom Cordyceps militaris has fibrin binding
      activity, which allows for the local activation of the fibrin degradation
      pathway.

PMID- 17205041
TI  - Characterization of beta-ketoadipate pathway from multi-drug resistance
      bacterium, Acinetobacter baumannii DU202 by proteomic approach.
AB  - In this study, the biodegradative activities of monocyclic aromatic compounds
      were determined from the multi-drug resistant (MDR) Acinetobacter baumannii,
      which were studied in the form of clinical isolates from a hospital in Korea.
      These bacteria were capable of biodegrading monocyclic aromatic compounds, such
      as benzoate and p-hydroxybenzoate. In order to determine which pathways are
      available for biodegradation in these stains, we conducted proteome analyses of
      benzoate and p-hydroxybenzoate-cultured A. baumannii DU202, using 2-DE/MS
      analysis. As genome DB of A. baumannii was not yet available, MS/MS analysis or
      de novo sequencing methods were employed in the identification of induced
      proteins. Benzoate branch enzymes [catechol 1,2-dioxygenase (CatA) and benzoate
      dioxygenase alpha subunit (BenA)] of the beta-ketoadipate pathway were identified
      under benzoate culture condition and p-hydroxybenzoate branch enzymes
      [protocatechuate 3,4-dioxygenase alpha subunit (PcaG) and 3-carboxy-cis,cis
      muconate cycloisomerase (PcaB)] of the beta-ketoadipate pathway were identified
      under p-hydroxybenzoate culture condition, respectively, thereby suggesting that
      strain DU202 utilized the beta-ketoadipate pathway for the biodegradation of
      monocyclic aromatic compounds. The sequence analysis of two purified dioxygenases
      (CatA and PcaGH) indicated that CatA is closely associated with the CatA of
      Acinetobacter radiresistance, but PcaGH is only moderately associated with the
      PcaGH of Acinetobacter sp. ADP1. Interestingly, the fused form of PcaD and PcaC,
      carboxymuconolactone decarboxylase (PcaCD), was detected on benzoate-cultured A.
      baumannii DU202. These results indicate that A. baumannii DU202 exploits a
      different beta-ketoadipate pathway from other Acinetobacter species.

PMID- 17205042
TI  - A new function of Skp1 in the mitotic exit of budding yeast Saccharomyces
      cerevisiae.
AB  - We previously reported that Skp1, a component of the Skp1-Cullin-F-box protein
      (SCF) complex essential for the timely degradation of cell cycle proteins by
      ubiquitination, physically interacts with Bfa1, which is a key negative regulator
      of the mitotic exit network (MEN) in response to diverse checkpoint-activating
      stresses in budding yeast. In this study, we initially investigated whether the
      interaction of Skp1 and Bfa1 is involved in the regulation of the Bfa1 protein
      level during the cell cycle, especially by mediating its degradation. However,
      the profile of the Bfa1 protein did not change during the cell cycle in skp1-11,
      which is a SKP1 mutant allele in which the function of Skp1 as a part of SCF is
      completely impaired, thus indicating that Skp1 does not affect the degradation of
      Bfa1. On the other hand, we found that the skp1-12 mutant allele, previously
      reported to block G2-M transition, showed defects in mitotic exit and
      cytokinesis. The skp1-12 mutant allele also revealed a specific genetic
      interaction with Deltabfa1. Bfa1 interacted with Skp1 via its 184 C-terminal
      residues (Bfa1-D8) that are responsible for its function in mitotic exit. In
      addition, the interaction between Bfa1 and the Skp1-12 mutant protein was
      stronger than that of Bfa1 and the wild type Skp1. We suggest a novel function of
      Skp1 in mitotic exit and cytokinesis, independent of its function as a part of
      the SCF complex. The interaction of Skp1 and Bfa1 may contribute to the function
      of Skp1 in the mitotic exit.

PMID- 17205043
TI  - Cloning and analysis of a type II polyketide synthase gene cluster from
      Streptomyces toxytricini NRRL 15,443.
AB  - A standard type II polyketide synthase (PKS) gene cluster was isolated while
      attempting to clone the biosynthetic gene for lipstatin from Streptomyces
      toxytricini NRRL 15,443. This result was observed using a Southern blot of a PstI
      digested S. toxytricini chromosomal DNA library with a 444 bp amplified probe of
      a ketosynthase (KS) gene fragment. Four open reading frames [thioesterase (TE),
      beta-ketoacyl systhase (KAS), chain length factor (CLF), and acyl carrier protein
      (ACP)], were identified through the nucleotide sequence determination and
      analysis of a 4.5 kb cloned DNA fragment. In order to confirm the involvement of
      a cloned gene in lipstatin biosynthesis, a gene disruption experiment for the KS
      gene was performed. However, the resulting gene disruptant did not show any
      significant difference in lipstatin production when compared to wild-type S.
      toxytricini. This result suggests that lipstatin may not be synthesized by a type
      II PKS.

PMID- 17205044
TI  - Molecular phylogenetic analysis of HIV-1 vif gene from Korean isolates.
AB  - Phylogenetic studies of nef, pol, and env gene sequences of HIV-1 isolated from
      Koreans suggested the presence of a Korean clade in which Korean sequences are
      clustered to the exclusion of foreign sequences. We attempted to identify and
      characterize the Korean clade using all vif gene sequences isolated from Koreans
      registered in the NCBI GenBank database (n = 233). Most (77 %) of the Korean
      isolates belonged to the Korean clade as a large subcluster in subtype B,
      designated the Korean clade subtype B (KCB). KCB sequences were relatively
      homogenous compared to Korean subtype B sequences that did not belong to the KCB
      (non-Korean clade subtype B; NKCB). Comparison of amino acid frequencies of KCB
      and NKCB sequences revealed several positions where the amino acid frequencies
      were significantly different. These amino acid residues were critical in
      separating KCB from NKCB or from foreign sequences, since substitution of these
      amino acids in KCB with the NKCB amino acids relocated the KCB sequences to NKCB,
      and vice versa. Further analyses of KCB will help us to understand the origin and
      evolutionary history of KCB.

PMID- 17205045
TI  - Claritromycin resistance and Helicobacter pylori genotypes in Italy.
AB  - The relationship between H. pylori clarithromycin resistance and genetic pattern
      distribution has been differently explained from different geographic areas.
      Therefore, we aimed to assess the clarithromycin resistance rate, to evaluate the
      bacterial genetic pattern, and to search for a possible association between
      clarithromycin resistance and cagA or vacA genes. This prospective study enrolled
      62 consecutive H. pylori infected patients. The infection was established by
      histology and rapid urease test. Clarithromycin resistance, cagA and vacA status,
      including s/m subtypes, were assessed on paraffin-embedded antral biopsy
      specimens by TaqMan real time polymerase chain reaction (PCR). Primary
      clarithromycin resistance was detected in 24.1 % of cases. The prevalence of cagA
      was 69.3 %, and a single vacA mosaicism was observed in 95.1 % cases. In detail,
      the s1m1 was observed in 23 (38.9 %) patients, the s1m2 in 22 (37.2 %), and the
      s2m2 in 14 (23.7 %), whereas the s2m1 combination was never found. The prevalence
      of cagA and the vacA alleles distribution did not significantly differ between
      susceptible and resistant strains. Primary clarithromycin resistance is high in
      our area. The s1m1 and s1m2 are the most frequent vacA mosaicisms. There is no a
      relationship between clarithromycin resistance and bacterial genotypic pattern
      and/or cagA positivity.

PMID- 17205046
TI  - Effect of mycelial extract of Clavicorona pyxidata on the production of amyloid
      beta-peptide and the inhibition of endogenous beta-secretase activity in vitro.
AB  - Amyloid beta-peptide (Abeta), which is a product of the proteolytic effect of
      beta-secretase (BACE) on an amyloid precursor protein, is closely associated with
      Alzheimer's disease (AD) pathogenesis. There is sufficient evidence to suggest
      that a BACE inhibitor may reduce Abeta levels, thus decreasing the risk of AD. In
      a previous study, an extract of Clavicorona pyxidata DGUM 29005 mycelia was found
      to inhibit the production of a soluble beta-amyloid precursor protein (sbetaAPP),
      Abeta, and BACE in neuronal cell lines. We sought to determine whether this
      mycelial extract exerts the same effect in human rhabdomyosarcoma A-204 and rat
      pheochromocytoma PC-12 cells. We found that the production of Abeta decreased in
      a dose-dependent manner in the presence of the mycelial extract and that the
      concentration of Abeta never exceeded 50 microg/ml. The presence of sAPP was
      detected in every culture medium to which the mycelial extract had been added and
      its concentration remained the same, regardless of the concentration of the
      extract used. Endogenous beta-secretase activity in A-204 and PC-12 cellular
      homogenates also decreased in the presence of this extract. These cells, in
      culture, were not susceptible to the cytotoxic activity of the mycelial extract.

PMID- 17205047
TI  - Construction of an Escherichia-Pseudomonas shuttle vector containing an
      aminoglycoside phosphotransferase gene and a lacZ'' Gene for alpha
      complementation.
AB  - A new 4.87 kb Escherichia-Pseudomonas shuttle vector has been constructed by
      inserting a 1.27 kb DNA fragment with a replication origin of a Pseudomonas
      plasmid pRO1614 into the 3.6 kb E. coli plasmid pBGS18. This vector, designated
      pJH1, contains an aminoglycoside phosphotransferase gene (aph) from Tn903, a
      lacZ'' gene for alpha-complementation and a versatile multiple cloning site
      possessing unique restriction sites for EcoRI, SacI, KpnI, SmaI, BamHI, XbaI,
      SalI, BspMI, PstI, SphI, and HindIII. When pJH1 was transformed into E. coli
      DH5alpha and into P. putida HK-6, it was episomally and stably maintained in both
      strains. In addition, the enhanced green fluorescent protein (EGFP) gene which
      was transcriptionally cloned into pJH1 rendered E. coli cells fluorescence when
      its transformants were illuminated at 488 nm.

PMID- 17205048
TI  - Diversity of yeasts associated with Panax ginseng.
AB  - Biodiversity of yeasts was investigated in the ginseng cultivation field. Among
      34 isolates tested in this study, 26 isolates belonged to the hymenomycetous
      yeast group. These 26 strains were classified into 12 species including four new
      species candidates that did not have clear affiliation to any established
      species. Seven isolates among the remaining strains were classified into three
      ascomycetous yeast species, and one isolate was identified as a urediniomycetous
      yeast species.

PMID- 17205049
TI  - Isolation of quinolone-resistant Escherichia coli found in major rivers in Korea.
AB  - Twenty isolates resistant to seven quinolones were isolated from major rivers in
      Korea. All isolates had three mutations, Ser83-->Leu and Asp87-->Asn in GyrA and
      Ser80-->Ile or Ser80-->Arg in ParC and three isolates had an additional mutation
      Glu84-->Gly or Glu84-->Val in ParC. In addition, a clonal spread was not found in
      these isolates.

PMID- 17205050
TI  - The molecular characterization of serogroup C Neisseria meningitidis strains
      circulating in Beijing.
AB  - The aim of this study was to characterize the molecular features of serogroup C
      Neisseria meningitidis strains circulating in Beijing, China. Twenty out of 23
      strains belonged to ST 4821. The causative serosubtype for meningococcal
      meningitis was P1.12-1,16-8. All of the strains expressed class 3 PorB protein.
      Among the five pulsed-field gel electrophoresis patterns observed, pattern III
      predominated.

PMID- 17205051
TI  - Carbon source-dependent regulation of the Schizosaccharomyces pombe pbh1 gene.
AB  - Pbh1, from the fission yeast Schizosaccharomyces pombe, is a baculoviral
      inhibitor of apoptosis (IAP) repeat (BIR) domain-containing protein. Its unique
      encoding gene was previously found to be regulated by nitric oxide and nitrogen
      starvation. In the current work, the Pbh1-lacZ fusion gene was used to elucidate
      the transcriptional regulation of the pbh1 gene under various carbon sources.
      When fermentable carbon sources, such as glucose (at a low concentration of
      0.2%), sucrose (2.0%) and lactose (2.0%), were the sole carbon source, the
      synthesis of beta-galactosidase from the Pbh1-lacZ fusion gene was reasonably
      enhanced. However, the induction by these fermentable carbon sources was
      abolished in the Pap1-negative S. pombe cells, implying that this type of
      induction of the pbh1 gene is mediated by Pap1. Ethanol (2.0%), a nonfermentable
      carbon source, was also able to enhance the synthesis of beta-galactosidase from
      the fusion gene in wild-type cells but not in Pap1-negative cells. The results
      indicate that the S. pombe pbh1 gene is up-regulated under metabolic oxidative
      stress in a Pap1-dependent manner.

PMID- 17205052
TI  - Marine bacteria associated with the Korean brown alga, Undaria pinnatifida.
AB  - Several marine bacterial strains were isolated from Undaria pinnatifida (Miyok in
      Korean). Sixty-six strains were isolated on R2A agar media at 10 degrees and
      identified by a phylogenetic analysis of the 16S rRNA gene sequences. They were
      grouped into 10 different sequence types based on the initial sequence analysis
      of the 5' domain of the gene (approximately 500 bp). Full sequences of 16S rRNA
      gene were obtained from one strain in each sequence type and the species
      affiliation was determined using phylogenetic and sequence similarity analyses.
      The results of the analyses indicated that they were closely related to
      Psychrobacter aquimaris, P. celer, P. nivimaris, P. pulmonis, Psychromonas
      arctica or Bacillus psychrodurans. These bacteria are marine or psychrotrophic
      bacteria. Because the sporophytes of U.pinnatifida are cultured on the costal
      area during winter, the U. pinnatifida-associated bacteria appeared to grow at
      low temperatures. U. pinnatifida sporophytes can be a good source for the
      isolation of psychrotrophic bacteria.

PMID- 17205055
TI  - Wilms' tumour 1 mutations are associated with FLT3-ITD and failure of standard
      induction chemotherapy in patients with normal karyotype AML.

PMID- 17205056
TI  - Antitumor activity of sorafenib in FLT3-driven leukemic cells.
AB  - Activating internal tandem duplication (ITD) insertions in the juxtamembrane
      domain of the FLT3 tyrosine kinase are found in about one fourth of patients with
      acute myeloid leukemia and have been shown to be an independent negative
      prognostic factor for survival. We show that sorafenib (BAY 43-9006, Nexavar)
      potently inhibits FLT3 enzymatic and signaling activities. In HEK293 cells stably
      transfected with FLT3-WT or FLT3-ITD, sorafenib blocked basal and ligand
      dependent FLT3-mediated tyrosine autophosphorylation as well as extracellular
      signal-regulated kinase1/2 and Stat5 phosphorylation. In leukemia cell lines MV4
      11 and EOL-1, sorafenib treatment resulted in decreased cell proliferation and
      inhibition of FLT3 signaling. The growth of the FLT3-independent RS4-11 cell line
      was only weakly inhibited by sorafenib. Cell cycle arrest and induction of
      apoptosis were observed upon treatment with sorafenib in MV4-11 and EOL-1 cells.
      The antitumor efficacy of sorafenib was evaluated against the MV4-11 leukemia
      grown subcutaneously in NCr nu/nu mice. Doses of 3 and 10 mg/kg administered
      orally for 14 days resulted in six and nine out of 10 animals with complete
      responses, respectively. The demonstration that sorafenib exhibits potent target
      inhibition and efficacy in FLT3-driven models suggests that this compound may
      have a therapeutic benefit for patients with FLT3-driven leukemias.

PMID- 17205057
TI  - Outcome of patients with acute promyelocytic leukemia failing to front-line
      treatment with all-trans retinoic acid and anthracycline-based chemotherapy
      (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention.
AB  - To determine prognosis of acute promyelocytic leukemia (APL) failing to front
      line therapy with all-trans retinoic acid (ATRA) and anthracyclines, outcome of
      52 patients (32 M/20 F; age: 37, 3-72) included in PETHEMA trials LPA96 and LPA99
      who presented with either molecular failure (MOLrel, n=16) or hematological
      relapse (HEMrel, n=36) was analyzed. Salvage therapy consisted of ATRA and high
      dose ara-C-based chemotherapy (HDAC) in most cases (83%), followed by stem-cell
      transplantation (autologous, 18; allogeneic, 10; syngeneic, 1). Fourteen patients
      with MOLrel (88%) achieved second molecular complete response (molCR), whereas
      81% HEMrel patients responded to second-line treatment, with 58% molCR. After
      median follow-up of 45 months, four MOLrel and 18 HEMrel patients, respectively,
      experienced a second relapse. Outcome after MOLrel compared favorably to HEMrel,
      with longer survival (5-year survival: 64+/-14 vs 24+/-8%, P=0.01) and lower
      relapse risk (5-year relapse risk: 30+/-13 vs 64+/-9%; P=0.044). Additionally,
      age <or=40 and male gender were favorable variables for survival, whereas
      molecular response predicted longer leukemia-free survival. In conclusion, early
      institution of salvage therapy at molecular failure, before onset of
      hematological relapse, is beneficial in APL. Moreover, given the poor outcome of
      HEMrel managed with ATRA and HDAC, use of alternative therapeutic strategies in
      this setting is warranted.

PMID- 17205058
TI  - Clinical and prognostic significance of cytokine receptor expression in adult
      acute lymphoblastic leukemia: interleukin-2 receptor alpha-chain predicts a poor
      prognosis.
AB  - We quantitatively assessed the expression of cytokine receptors (interleukin-2
      receptor (IL-2R), IL-3R, IL-4R, IL-5R, IL-6R, IL-7R, granulocyte-macrophage
      colony-stimulating factor R (GM-CSFR), G-CSFR, c-fms, c-mpl, c-kit and FLT3) in
      cells from 211 adults with acute lymphoblastic leukemia (ALL) by flow cytometry
      and determined their prevalence and clinical significance. Although all cytokine
      receptors were expressed to various degrees, the levels of IL-3R alpha-chain (IL
      3Ralpha), IL-2Ralpha, IL-2Rbeta, IL-7Ralpha, common-Rgamma(gammac), c-mpl, c-kit
      and FLT3 exhibited a wide spectrum > or =2000 sites/cell. Among them, IL-3Ralpha,
      IL-2Ralpha and FLT3 were highly expressed in B-lineage ALL, whereas IL-7Ralpha,
      gammac and c-kit predominated in T-lineage ALL. Higher levels of IL-3Ralpha, IL
      2Ralpha, c-kit and FLT3 correlated with the expression of CD13/33. Increased IL
      2Ralpha levels related to the presence of Philadelphia chromosome (Ph),
      leukocytosis and shorter event-free survival (EFS). C-kit preferred in male.
      Elevated FLT3 levels correlated with age > or =60 years. Multivariate analysis in
      B-lineage ALL revealed only IL-2Ralpha (P=0.028) and Ph (P=0.020) as independent
      factors for EFS. These findings suggest that several cytokine receptors
      associated with certain cellular and clinical features, but IL-2Ralpha solely had
      a prognostic value and should be considered as a major prognostic factor for
      adult ALL that is comparable with Ph.

PMID- 17205059
TI  - Acute differentiated dendritic cell leukemia: a variant form of pediatric acute
      myeloid leukemia with MLL translocation.

PMID- 17205060
TI  - Epidermal transglutaminase deposits in perilesional and uninvolved skin in
      patients with dermatitis herpetiformis.

PMID- 17205061
TI  - Evidence for a novel psoriasis susceptibility locus at 9q33-9q34 in Chinese Hans.
AB  - Psoriasis is a heterogeneous disease for which nine linkage loci (PSORS loci 1-5
      and PSORS7-10) have been accepted by the Human Genome Nomenclature Committee and
      an additional 16 potential susceptibility loci have been reported so far. Our
      previous genome-wide scan in 61 Chinese Han psoriasis vulgaris families found two
      susceptibility loci at 6p21.3 and 4q31 and additional suggestive linkage evidence
      at other regions, including 9q33. In this follow-up study, the linkage evidence
      at 9q33 was further investigated using an expanded sample of 160 families and
      improved marker coverage. Our follow-up linkage analysis of the 160 families
      demonstrated strong linkage evidence (P < or = 0.000022) throughout a region
      between 133.38 and 146.23 cM with a maximum nonparametric linkage (NPL) score of
      4.64 (P = 0.00000023) and a heterogeneity LOD (HLOD) score of 5.03 (alpha = 46%)
      at 142.39 cM near the marker D9S290. By stratifying the 160 families into the
      subtypes of 130 early-onset and 30 late-onset families, we revealed stronger
      linkage evidence in the early-onset psoriasis families with a maximum multipoint
      HLOD score of 6.48 (alpha = 58%) and a maximum NPL score of 4.69 (P = 0.00000012)
      near marker D9S290. Our follow-up study has confirmed a novel susceptibility
      locus at 9q33-34 for early-onset psoriasis in the Chinese population.

PMID- 17205062
TI  - The role of proline-rich protein tyrosine kinase 2 in differentiation-dependent
      signaling in human epidermal keratinocytes.
AB  - Non-receptor tyrosine kinase proline-rich protein tyrosine kinase 2 (Pyk2)
      functions as an integrator of multiple signaling pathways involved in the
      regulation of fundamental cellular processes. Pyk2 expression, regulation, and
      functions in skin have not been examined. Here we investigated the expression and
      subcellular localization of Pyk2 in human epidermis and in primary human
      keratinocytes, and studied the mechanisms of Pyk2 activation by differentiation
      inducing stimuli, and the role of Pyk2 as a regulator of keratinocyte
      differentiation. We demonstrate that Pyk2 is abundantly expressed in skin
      keratinocytes. Notably, the endogenous Pyk2 protein is predominantly localized in
      keratinocyte nuclei throughout all layers of healthy human epidermis, and in
      cultured human keratinocytes. Pyk2 is activated by treatment with keratinocyte
      differentiating agents, 12-O-tetradecanoylphorbol-13-acetate and calcium via a
      mechanism that requires intracellular calcium release and functional protein
      kinase C (PKC) and Src activities. Particularly, differentiation-promoting PKC
      delta and PKC eta elicit Pyk2 activation. Our data show that Pyk2 increases
      promoter activity and endogenous protein levels of involucrin, a marker of
      keratinocyte terminal differentiation. This regulation is associated with
      increased expression of Fra-1 and JunD, activator protein-1 transcription factors
      known to be required for involucrin expression. Altogether, these results provide
      insights into Pyk2 signaling in epidermis and reveal a novel role for Pyk2 in
      regulation of keratinocyte differentiation.

PMID- 17205063
TI  - Child neurology: a separate and necessary discipline.

PMID- 17205064
TI  - Strategies for therapy in acute ischemic stroke.

PMID- 17205065
TI  - Headache in the emergency department--how to identify patients at risk of serious
      underlying pathology.

PMID- 17205066
TI  - Is there a link between aspirin therapy and stroke severity?

PMID- 17205067
TI  - Should patients with anaplastic oligodendroglial tumors receive adjuvant
      chemotherapy?

PMID- 17205068
TI  - Complex regional pain syndrome--are we neglecting neglect?

PMID- 17205069
TI  - Do all patients with Duchenne muscular dystrophy require surgery for the
      correction of scoliosis?

PMID- 17205070
TI  - Do poststroke MRI findings predict the type of a subsequent stroke?

PMID- 17205071
TI  - Do patients with neurocysticercosis benefit from cysticidal therapy?

PMID- 17205072
TI  - Primary CNS lymphoma.
AB  - Non-Hodgkin's lymphoma invades the brain, the vitreous body and nerves of the
      eye, the meninges, and the nerve roots of brain and spine, leading to the
      development of a primary CNS lymphoma. The mechanism of involvement of these
      locations by malignant B lymphocytes is unknown, but it might involve molecular
      targeting of lymphoma cells generated at cryptic systemic sites. The diagnosis of
      primary CNS lymphoma has been facilitated by advances in imaging techniques and
      the discovery of molecular markers. Methotrexate-based regimens, even when
      radiation is deferred, prolong overall survival to over 5 years, but relapses
      eventually occur in most cases. Better tools for earlier diagnosis and monitoring
      of treatment response will emerge from molecular studies of therapeutic targets.

PMID- 17205073
TI  - Drug Insight: the use of intravenous immunoglobulin in neurology--therapeutic
      considerations and practical issues.
AB  - Over the past few years, we have achieved increasing success in the treatment of
      a number of autoimmune-mediated disorders affecting nerves and muscles. This
      success is partly attributable to the use of high-dose polyclonal intravenous
      immunoglobulin (IVIg), which has dramatically changed our treatment options. On
      the basis of results from controlled, but non-FDA-approved, clinical trials, IVIg
      is now the treatment of choice for Guillain-Barre syndrome, chronic idiopathic
      inflammatory demyelinating polyneuropathy and multifocal motor neuropathy; IVIg
      offers rescue therapy for patients with rapidly worsening myasthenia gravis, and
      is a second-line therapy for dermatomyositis, stiff-person syndrome, and
      pregnancy-associated or postpartum multiple sclerosis attacks. The ability of
      IVIg to treat such immunologically diverse disorders effectively, coupled with
      its excellent safety profile, has led clinicians to use the drug more liberally,
      even in diseases for which the data are weak and not evidence-based and in
      patients with coexisting conditions. Use of IVIg for such indications can
      increase the risk of complications while raising the cost of the drug. Practical
      issues regarding dosing and frequency of infusions generate dilemmas in clinical
      practice. In this article, we review the current indications for IVIg treatment,
      address practical issues related to the use and costs of the drug, and summarize
      its mechanisms of action.

PMID- 17205074
TI  - Technology Insight: recanalization with drugs and devices during acute ischemic
      stroke.
AB  - Revascularization therapy is pivotal to saving ischemic brain from infarction.
      Two major randomized trials of intravenous thrombolytic therapy have established
      clear clinical benefit, especially for strokes caused by small-vessel occlusion.
      Ischemic stroke caused by large-vessel intracranial occlusion carries higher
      morbidity, however, and intravenous thrombolytics are less capable of opening
      these large vessels. This observation makes a case for delivering thrombolytics
      directly into the clot, or simply removing the clot mechanically. Intra-arterial
      thrombolytic drugs have been shown to be effective for treating middle cerebral
      artery occlusions in a major randomized trial. In the past 2 years, a family of
      mechanical thrombectomy catheters designed to remove rather than dissolve the
      offending clot has received FDA clearance. Such devices offer alternative therapy
      to patients who cannot receive thrombolytics, and can also be used in combination
      with thrombolytics to safely restore cerebral perfusion. Mechanical techniques
      have not been directly compared with intra-arterial thrombolytic strategies, but
      these devices might be superior to thrombolytics within vessels with particularly
      high clot burden, such as the carotid terminus and the basilar artery.
      Comprehensive stroke centers are currently available in major metropolitan areas
      to treat stroke via intra-arterial means, and are likely to become 'hubs' to
      'spoke' hospitals that are credentialed as primary stroke centers. This design
      will allow any patient timely access to state-of-the-art stroke treatment
      tailored to their needs.

PMID- 17205075
TI  - Superficial siderosis: a case report and review of the literature.
AB  - BACKGROUND: A 48-year-old man with a past history of a car-accident-induced coma
      at the age of 3 years and spontaneous bilateral subdural hematomas at the age of
      34 years presented with a 2-year history of worsening gait difficulties,
      clumsiness and dysarthria. CT scans of the brain taken during the 6 months
      leading up to his presentation had revealed chronic subarachnoid hemorrhage, but
      angiograms had not been able to identify the source of bleeding. INVESTIGATIONS:
      Neurological examination, brain MRI scan, lumbar puncture, four-vessel cerebral
      angiogram and spinal angiogram. DIAGNOSIS: Superficial siderosis; a complete
      review of the current literature on the condition is provided. MANAGEMENT: Iron
      chelating agents.

PMID- 17205076
TI  - Mammalian SGO2 appears at the inner centromere domain and redistributes depending
      on tension across centromeres during meiosis II and mitosis.
AB  - Shugoshin (SGO) is a family of proteins that protect centromeric cohesin
      complexes from release during mitotic prophase and from degradation during
      meiosis I. Two mammalian SGO paralogues - SGO1 and SGO2 - have been identified,
      but their distribution and function during mammalian meiosis have not been
      reported. Here, we analysed the expression of SGO2 during male mouse meiosis and
      mitosis. During meiosis I, SGO2 accumulates at centromeres during diplotene, and
      colocalizes differentially with the cohesin subunits RAD21 and REC8 at metaphase
      I centromeres. However, SGO2 and RAD21 change their relative distributions during
      telophase I when sister-kinetochore association is lost. During meiosis II, SGO2
      shows a striking tension-dependent redistribution within centromeres throughout
      chromosome congression during prometaphase II, as it does during mitosis. We
      propose a model by which the redistribution of SGO2 would unmask cohesive
      centromere proteins, which would be then released or cleaved by separase, to
      trigger chromatid segregation to opposite poles.

PMID- 17205077
TI  - Molecular determinants of the subcellular localization of the Drosophila Bcl-2
      homologues DEBCL and BUFFY.
AB  - The Bcl-2-family of proteins localize to intracellular membranes via a C-terminal
      hydrophobic membrane anchor (MA) domain, to exert their antiapoptotic or
      proapoptotic functions. In Drosophila, both Bcl-2 family members, DEBCL and
      BUFFY, contain an MA. In DEBCL the MA is necessary for the localization of
      protein to mitochondria and for its proapoptotic activity. BUFFY is highly
      similar to DEBCL but its localization and function are not clearly defined. Here,
      we report on comparative analysis of BUFFY and DEBCL to decipher the molecular
      basis for their subcellular localization. We show that these two proteins
      localize to distinct intracellular membranes, DEBCL predominantly to mitochondria
      and BUFFY to endoplasmic reticula (ER). Our results suggest that the MA-flanking
      residues in DEBCL, homologous to Bcl-X(L), are required for the targeting of
      DEBCL to mitochondria. The C-terminal positively charged residues present in
      DEBCL are absent in BUFFY, which allows for its localization to ER. The MA in
      both proteins is required for the correct targeting and proapoptotic activities
      of these proteins. Interestingly, a functional nuclear localization signal was
      identified in the N-terminal region of BUFFY and in the absence of the MA, BUFFY
      accumulated in the nucleus. The functional implications of these findings are
      discussed.

PMID- 17205078
TI  - Bcl-2 family proteins are essential for platelet survival.
AB  - Platelets are relatively short-lived, anucleated cells that are essential for
      proper hemostasis. The regulation of platelet survival in the circulation remains
      poorly understood. The process of platelet activation and senescence in vivo is
      associated with processes similar to those observed during apoptosis in nucleated
      cells, including loss of mitochondrial membrane potential, caspase activation,
      phosphatidylserine (PS) externalization, and cell shrinkage. ABT-737, a potent
      antagonist of Bcl-2, Bcl-X(L), and Bcl-w, induces apoptosis in nucleated cells
      dependent on these proteins for survival. In vivo, ABT-737 induces a reduction of
      circulating platelets that is maintained during drug therapy, followed by
      recovery to normal levels within several days after treatment cessation. Whole
      body scintography utilizing ([111])Indium-labeled platelets in dogs shows that
      ABT-737-induced platelet clearance is primarily mediated by the liver. In vitro,
      ABT-737 treatment leads to activation of key apoptotic processes including
      cytochrome c release, caspase-3 activation, and PS externalization in isolated
      platelets. Despite these changes, ABT-737 is ineffective in promoting platelet
      activation as measured by granule release markers and platelet aggregation. Taken
      together, these data suggest that ABT-737 induces an apoptosis-like response in
      platelets that is distinct from platelet activation and results in enhanced
      clearance in vivo by the reticuloendothelial system.

PMID- 17205079
TI  - Regulation of the Drosophila ubiquitin ligase DIAP1 is mediated via several
      distinct ubiquitin system pathways.
AB  - Inhibitors of apoptosis proteins (IAPs) suppress cell death by inactivating
      proapoptotic regulators, and therefore play important roles in controlling
      apoptosis in normal and malignant cells. Many IAPs are ubiquitin ligases, and
      their activity is mediated via ubiquitination and subsequent degradation of their
      targets. Here we corroborate a previous observation that DIAP1 (Drosophila IAP1)
      can be degraded via a two-step mechanism: (i) limited caspase-mediated cleavage
      and (ii) degradation of the released fragment via the ubiquitin N-end rule
      pathway. Yet, we demonstrate that this pathway is not the only one involved in
      DIAP1 degradation, and the intact protein can be degraded independent of prior
      caspase cleavage. Importantly, this mode of degradation does not require the RING
      finger-mediated autoubiquitinating activity of DIAP1, believed to target many
      RING-finger E3s for self-destruction. Our preliminary data suggest that DIAP2
      mediates DIAP1 degradation, suggesting a novel regulatory loop within the
      apoptotic pathway. Studying the role of the autoubiquitinating activity of DIAP1,
      we demonstrate that it does not involve formation of Lys48-based polyubiquitin
      chains, but probably chains linked via Lys63. Our preliminary data suggest that
      the autoubiquitination serves to attenuate the ligase activity of DIAP1 towards
      its exogenous substrates.

PMID- 17205080
TI  - [Experiences, expectations and intentions].

PMID- 17205081
TI  - [Morbid obesity].

PMID- 17205082
TI  - [Use of out-of-hours services before and after introduction of a patient list
      system].
AB  - BACKGROUND: Our aim was to better understand why inhabitants in a typical
      Norwegian town use out-of-hours services in primary care, and whether
      introduction of a patient list system (Fastlegeordningen) in 2001 had any
      influence on this choice. We analyzed changed use of out-of-hours service in
      Stavanger, Norway (approx. 110,000 inhabitants) from 1989 to 2002. METHODS:
      Changes in the number of consultations and home visits between 4 to 11 pm seven
      days a week, were assessed in the light of changes in operational presumptions
      for both the out-of-hours service and the family physicians' day-time service.
      RESULTS: There was a steady increase in the number of consultations and home
      visits from 1989 to 1997, except for in 1994. The absolute increase in the
      proportion of the population who sought this kind of care was 4.6%, i.e. a
      relative increase of 20%. From 1997 to 2002, there was an absolute decrease in
      consultations and home visits of 5.3%, or a 19% relative reduction. The
      percentage of patient encounters in patients' homes, decreased from 25% in 1989
      to 11% in 2002. The number of consultations and home visits in the evenings
      during the first 17 months after the list system was introduced, decreased
      (absolute value) with 2.2% (1.7-2.6), i.e. a 10% relative decrease, as compared
      to those during a similar period two years earlier. INTERPRETATION: A 20 % change
      in the use of out-of-hours service during few years, indicates that patients have
      used the service for other purposes than the intended emergency care. The demand
      for out-of-hours service is most influenced by the availability of primary care
      physicians during daytime. The list system has most likely encouraged both
      doctors and patients to promote the "personal doctor" to solve everyday health
      emergencies during the day.

PMID- 17205083
TI  - [Autoimmune hepatitis in children].
AB  - BACKGROUND: Autoimmune mechanisms are involved in the pathogenesis of autoimmune
      hepatitis and primary sclerosing cholangitis. The disorders are rare but
      important to diagnose, as immunomodulating therapy can prevent liver failure.
      Cases of "overlap syndrome" between autoimmune hepatitis and primary sclerosing
      cholangitis are described. MATERIAL AND METHODS: We have studied the medical
      records of children diagnosed with hepatitis and cholangitis treated at
      Rikshospitalet University Hospital from 1986 through 2004. Symptoms, findings and
      disease course are presented. A general overview is given of autoimmune
      hepatitis, primary sclerosing cholangitis and overlap syndrome in children.
      RESULTS: 18 children were identified; 11 with autoimmune hepatitis, six with
      primary sclerosing cholangitis and one with overlap syndrome. Four of the
      children with primary sclerosing cholangitis had inflammatory bowel disease; two
      of them had ulcerative colitis and two had Crohn's disease. The patient with
      overlap syndrome had ulcerative colitis. Pathology was found in the liver
      biopsies of all the children. Sixteen patients were treated with prednisolone and
      azathioprine. Most of the children responded to immunomodulating therapy with
      normalization of liver function tests. Many relapsed while tapering steroids.
      None of the patients have needed a liver transplant. CONCLUSION: It is important
      to diagnose children with autoimmune liver disease, as children tend to respond
      well to immunomodulating therapy.

PMID- 17205084
TI  - [Scalp necrosis in temporal arteritis].
AB  - BACKGROUND: Temporal arteritis is a systemic granulomatous vasculitis affecting
      large and medium sized arteries. Scalp necrosis is a rare complication that can
      appear before, during and after treatment. MATERIAL AND METHODS: A patient with
      temporal arteritis and scalp necrosis is presented and relevant literature
      reviewed. RESULTS: Scalp necrosis is seen in a few patients with temporal
      arteritis. The skin manifestations are most often bilaterally distributed and
      localised to the frontal, parietal and temporal parts of the scalp. Scalp
      necrosis often signifies a severe and extensive vasculitis, and is therefore
      associated with a high incidence of other disease-related complications, among
      them visual disturbances and blindness. CONCLUSION: Awareness of scalp necrosis
      as a complication of temporal arteritis could reduce unnecessary time-consuming
      assessments and lead to a more rapid diagnosis and start of treatment.

PMID- 17205085
TI  - [Medical audits contribute to good and comparable health services].
AB  - In 2004, the board of Eastern Norwegian Regional Health Authority (HelseOst RHF)
      decided that medical audits should be carried out in the treatment of cerebral
      stroke and breast cancer and in the mental health services. The objective was to
      establish to what extent the best practice is followed, to learn from each other,
      and to obtain help and advice. The medical audits were based on guidelines in ISO
      and were carried out under the leadership of external medical audit leaders,
      medical experts and medical auditors from the region. The results show that, on
      the whole, the patients are offered satisfactory treatment, but improvement is
      needed. The number of breast-preserving operations could be increased, treatment
      should be offered in a cerebral stroke unit to all those with acute cerebral
      stroke and suicide assessments should be improved. Most improvement measures were
      started quickly and were followed up by directors and local boards. HelseOst RHF
      followed up the general improvement suggestions. The medical audits were well
      received by health enterprises. In order to carry out medical audits the
      following is needed; national medical standards or summarized information on the
      best practice where standards are not defined. The regional health enterprises
      can use medical audits to assess the standard of treatment in risk zones, thus
      ensuring that uniform services are available for the population. Medical audits
      provide a good tool for preserving quality.

PMID- 17205086
TI  - [Iodine prophylaxis following nuclear accidents].
AB  - Radioactive iodine isotopes may be released to air to a varying degree during
      accidents with nuclear reactors. Iodine tablets, taken before or shortly after
      such release, protect against intake of radioactive iodine isotopes, but not
      against other radionuclides. Iodine prophylaxis can be a relevant countermeasure
      in Norway and will be implemented according to recommendations from the Crisis
      Committee for Nuclear and Radiological Emergencies. The Chernobyl accident
      confirmed that the risk for radiogenic thyroid cancer is much higher for foetuses
      and children and adolescents under 18 years. An epidemiological study showed that
      intake of iodine tablets could reduce the risk for thyroid cancer by a factor of
      three. For children, the WHO has therefore recommended a 10 mGy avertable dose to
      the thyroid. The Norwegian Radiation Protection Authority acknowledge the WHO
      guidelines and advise that the first priority of all emergency preparedness
      planning for potential releases that can cause dispersion of radioactive iodine,
      should be given to the protection of pregnant and breast-feeding women, newborns
      and children under 18 years. Iodine tablets should be taken immediately
      (preferably not later than a few hours) in situations where inhalation of
      radioactive iodine may occur. It should be underlined that iodine prophylaxis is
      one of several emergency countermeasures; other measures are sheltering and
      evacuation. The latter two countermeasures will protect not only from intake of
      radioactive iodine, but also against other radionuclides that may be released.
      Based on the present risk assessment in Norway, iodine tablets have been
      distributed to the counties north of Salten. In addition, there is an emergency
      stockpile of iodine tablets in Oslo.

PMID- 17205087
TI  - [Has the obesity epidemic reached Norway?].
AB  - BACKGROUND: The prevalence of obesity has increased worldwide during the last
      decades. The goal of this article is to explore whether the obesity epidemic has
      reached Norway. MATERIAL AND METHODS: We have conducted a literature review where
      we identified and summarized recent population studies of prevalence,
      distribution and development trends of obesity among adults in Norway. We
      searched for articles from the last 5 years in PubMed, Google, Kvasir and Yahoo,
      with the search words "obes*", "prevalence" and "BMI". We included seven
      Norwegian population studies. RESULTS: In the studies from 2000-2003, the
      prevalence of obesity (BMI > or = 30) was 11-29% (median 19.5%) for men and 9-38%
      (median 20%) for women. The prevalence of obese men aged 40-45 years has
      increased steadily from 1965-69 until today. The prevalence of obese women
      decreased from 1965-69 to 1984 before it started to increase steadily up till
      2000-2003. INTERPRETATION: Our review shows that the obesity epidemic has reached
      Norway, but the prevalence among all age groups should be established before we
      can determine the epidemic's extent.

PMID- 17205088
TI  - [Surgical treatment of morbid obesity].
AB  - BACKGROUND: Patients with morbid obesity are prone to weight-related disease,
      reduced quality of life and shortened life expectancy. Long-term weight loss is
      unsatisfactory with conservative treatment and weight-reducing surgery is
      increasingly performed in all Norwegian health regions. METHODS: This review is
      based on electronic database searches. We describe the two procedures most
      commonly performed in Norway, i.e. gastric bypass and biliopancreatic diversion
      with duodenal switch, including preoperative workup and expected results after
      surgery. The domestic use of different surgical techniques is also outlined.
      RESULTS: In Norway, around 750 bariatric procedures were planned in 2006. Gastric
      bypass yields a weight reduction of 30% two years after the operative. Resolution
      of type 2-diabetes, hypertension, hyperlipidemia, and obstructive sleep apnea has
      been demonstrated in most patients. A majority of patients report improved
      quality of life. Procedure-related mortality is less than 1% and surgical
      complications occur in approximately 20%. Nutritional deficiencies are frequent.
      Weight loss is somewhat greater after biliopancreatic diversion with duodenal
      switch, but the procedure is more complex. Life-long follow-up is recommended
      after bariatric surgery. INTERPRETATION: In selected patients with morbid
      obesity, bariatric surgery is a viable treatment. However, prospective long- term
      studies are needed.

PMID- 17205089
TI  - [Laparoscopic gastric bypass surgery in extreme overweight at a private
      hospital].
AB  - BACKGROUND: Laparoscopic gastric bypass surgery leads to significant weight loss
      and reduced morbidity in patients with severe obesity. The technique was
      introduced at the private Aleris hospital the autumn 2005. We here present the
      method and results from our initial experience. MATERIAL AND METHODS: Inclusion
      criteria were BMI > 40 kg/m2 or BMI 35-39,9 kg/m2 , with obesity-related co
      morbidity for more than 5 years and insufficient effect of conservative
      treatment. The first 121 (103 women) consecutive patients who underwent gastric
      bypass surgery at Aleris Hospital were included. Characteristics were; mean age
      40 years (18-68), mean preoperative body weight 134 kg (91-211) and BMI 44 m/kg 2
      (35-64). Serious complications or major morbidity were defined as anastomosis- or
      intestinal leakage and bleeding requiring surgical treatment. RESULTS: No deaths
      or major morbidity was observed the first 30 days after surgery. One patient
      underwent successful surgery of a perforated ulcer localized distally to the
      gastro-jejunal anastomoses 3 months p.o. Mean operating time was 62 min (40-124)
      for patients who underwent isolated laparoscopic bypass. The mean hospitalisation
      time was 2.9 days (2-6). CONCLUSION: Our results demonstrate that bariatric
      surgery can be established successfully with a low rate of perioperative
      complications. We believe that thorough planning and experienced bariatric
      surgeons contribute to our favourable results. .

PMID- 17205090
TI  - [Surgical treatment of morbid obesity at a regional center].
AB  - BACKGROUND: Aker University Hospital has since 2004 offered laparoscopic surgery
      for morbid obesity. This study describes the characteristics of the patients
      undergoing surgery, the preoperative evaluation and the perioperative outcome
      after the first 139 laparoscopic procedures for morbid obesity. MATERIAL AND
      METHODS: All patients operated between June 2004 and March 2006 are included in
      the study. The registration of data was first retrospective, and from 2006
      prospective using specially designated registration forms. RESULTS: Surgery was
      performed on 105 women (76%) and 33 men. The median age was 39 years (range 22
      60), and the median preoperative body mass index was 47 kg/m2 (37-71). Frequent
      comorbidities included joint pain (44%), hypertension (31%), asthma (30%) and
      diabetes mellitus (27%). The patients underwent gastric bypass (86%), duodenal
      switch (10%) or gastric sleeve (4%). Two procedures (1%) were converted to open
      surgery. Perioperative morbidity (within 30 days) was 19%. The most frequent
      major complications were leakage from the stomach or bowel in seven patients
      (5%), intra-abdominal bleeding in four patients (3%) and deep infection (3%).
      Reoperation was performed on 13 patients (9%). One patient died following surgery
      (1%). INTERPRETATION: . Laparoscopic bariatric surgery has now been established
      at Aker University Hospital. The complication rates seem acceptable, considering
      the patients'comorbid conditions and the introduction of advanced laparoscopic
      procedures.

PMID- 17205091
TI  - [Nutritional status after surgical treatment of obesity].
AB  - BACKGROUND: Biliopancreatic bypass with duodenal switch is a treatment for morbid
      obesity that combines restriction of dietary intake with a high degree of
      malabsorption. The operation involves the risk of losing important nutritional
      elements. MATERIAL AND METHODS: 64 women and 14 men who had a biliopancreatic
      bypass with duodenal switch performed in 2002 - 2005 and were followed up at
      least once, six months or later after surgery, were examined with 3 to 6-month
      intervals for the following; body weight, clinical status, haematological
      variables, ferritin, folate, albumin, creatinine, retinol, alpha
      tocopherol/lipids, vitamin D metabolites, parathyroid hormone, vitamin B1,
      lipids, glucose and other clinical chemical variables. RESULTS: Weight loss after
      surgery was substantial and rapid, from a mean of 153.8 kg (SD 30.2) to 92.7 kg
      (SD 21.6) after one year (n = 74). Low values of serum albumin, creatinine,
      retinol, 25-OH vitamin D and elevated parathyroid hormone were very common. Four
      women and three men (9 % of all) with common channels of < 100 cm, required a
      surgical revision mainly due to hypoalbuminemia. Two women became pregnant before
      the recommended 18 months after surgery. INTERPRETATION: Biliopancreatic bypass
      with duodenal switch in patients with common channels < 100 cm, has a high rate
      of complications and nutritional deficiencies. This surgery should be used
      restrictively.

PMID- 17205092
TI  - [Prioritization and health--should maximum-price life years be introduced?].

PMID- 17205093
TI  - [Ethical assessment in preliminary evaluation of research].

PMID- 17205094
TI  - [Is the new St Olav Hospital on its way to collapse?].

PMID- 17205095
TI  - [Post-traumatic stress disorder?].

PMID- 17205096
TI  - [Heart arrhythmia and sudden death during methadone therapy].

PMID- 17205097
TI  - [Reflections from a non-specialist in psychiatry].

PMID- 17205099
TI  - [Platelet inhibition and gastric problems].

PMID- 17205100
TI  - [Metformin can cause vitamin B 12 deficiency in diabetes].

PMID- 17205103
TI  - [From cooperation to capitalism].

PMID- 17205105
TI  - Proteomic analyses to identify novel therapeutic targets for the treatment of
      advanced prostate cancer.
AB  - At present there is no cure for advanced prostate cancer once it progresses to an
      androgen independent stage. Hormonal therapy, radiotherapy, and chemotherapy all
      have limited durations of efficacy for men diagnosed with androgen independent
      disease and patients will succumb over a period of several months to two years.
      The androgen receptor (AR) has been suspected to play an important role in the
      mechanism of progression to androgen independence. This is because the AR is a
      transcription factor that 'normally' mediates the effects of androgen to regulate
      expression of genes involved in proliferation and survival of prostate cells.
      Thus identifying and characterizing the proteins that interact with the AR to
      facilitate an activated receptor is of critical importance. Proteomic approaches
      such as isotope-coded affinity tags (ICAT), isotope Tags for Relative and
      Absolute Quantification (iTRAQ)(TM), Stable Isotope Labeling with Amino acids in
      Cell culture (SILAC), Tandem Affinity Purification (TAP) of tagged proteins (TAP
      tag) and Multidimensional Protein Identification Technology (MudPIT) provide
      large scale unbiased strategies and have not been previously applied to identify
      proteins that interact with the AR. Here an example of the power of these
      proteomic approaches to identify potential therapeutic targets for prostate
      cancer is provided. Application of MudPIT identified 82 peptides in endogenous
      complexes immunoprecipitated with the AR from prostate cancer cells.
      Identification of these novel proteins may ultimately lead to the development of
      better therapies for the treatment or prevention of advanced prostate cancer.

PMID- 17205106
TI  - Role of TAB1 in nitric oxide-induced p38 activation in insulin-producing cells.
AB  - The aim of present study was to elucidate the role of TAB1 in nitric oxide
      induced activation of p38 MAPK. For this purpose we over-expressed TAB1 in
      insulin-producing beta-TC6 cells. We observed in cells transiently over
      expressing TAB1 that p38 activation was enhanced in response to DETA/NONOate. A
      lowering of TAB1 levels, using the siRNA technique, resulted in the opposite
      effect. The DETA/NONOate-induced cell death rate was increased in cells
      transiently overexpressing TAB1. In stable beta-TC6 cell clones with very high
      TAB1 levels p38 phosphorylation was enhanced also at basal conditions.
      DETA/NONOate increased also the phosphorylation of JNK and ERK in beta-TC6 cells,
      but these events were not affected by TAB1. Interestingly, the inhibitory effect
      of SB203580 on p38 phosphorylation was paralleled by a stimulatory effect on JNK
      phosphorylation and an inhibitory effect on ERK phosphorylation. In summary, we
      propose that TAB1 promotes nitric oxide-induced p38 autophosphorylation. In
      addition, nitric oxide-induced p38 activation seems to promote JNK inhibition and
      ERK activation, but this effect appears to not require TAB1. A better
      understanding of how the TAB1/p38 pathway promotes beta-cell death in response to
      nitric oxide might help in the development of novel pharmacological approaches in
      the treatment of diabetes.

PMID- 17205107
TI  - The environmental-endocrine basis of gynandromorphism (intersex) in a crustacean.
AB  - Commensurate with the decline in many crustacean populations has been an
      accumulation in reports of sexually ambiguous individuals within these
      populations. The cause of gynandromorphism or intersex among crustaceans is
      unknown. We show that gynandromorphism in the branchiopod crustacean Daphnia
      magna is initiated by the sex-determining hormone methyl farnesoate when levels
      of the hormone are intermediate between low levels that stimulate the production
      of broods containing all female offspring and high levels that stimulate the
      production of broods of all male offspring. The incidence of hormonally-induced
      gynandromorphism was low (0.14% at the maximum stimulatory hormone
      concentrations) but was significantly increased (46-fold) when the animals were
      hormone-treated at 30 degrees C. Some environmental chemicals also can stimulate
      the gynandromorphic phenotype as we demonstrated with the insecticide
      pyriproxyfen. Gynandromorphism occurs due to inadequate signaling of male-sex
      determination since: a) gynandromorphs did not occur in a population that was
      producing only female offspring; and, b) conditions that stimulated
      gynandromorphism also reduced the incidence of male offspring. We suggest that
      male sex determination normally occurs prior to the first embryonic cleavage.
      Elevated temperature may alter the timing of sex determination such that methyl
      farnesoate signaling occurs after the first embryonic cleavage and bilateral
      gynandromorphism occurs as a consequence of signaling to only one of the daughter
      cells. These results demonstrate that environmental factors can cause aberrant
      sex determination via perturbations in methyl farnesoate signaling.

PMID- 17205108
TI  - A complete mitochondrial genome sequence of Asian black bear Sichuan subspecies
      (Ursus thibetanus mupinensis).
AB  - We obtained the complete mitochondrial genome of U.thibetanus mupinensis by DNA
      sequencing based on the PCR fragments of 18 primers we designed. The results
      indicate that the mtDNA is 16,868 bp in size, encodes 13 protein genes, 22 tRNA
      genes, and 2 rRNA genes, with an overall H-strand base composition of 31.2% A,
      25.4% C, 15.5% G and 27.9% T. The sequence of the control region (CR) located
      between tRNA-Pro and tRNA-Phe is 1422 bp in size, consists of 8.43% of the whole
      genome, GC content is 51.9% and has a 6bp tandem repeat and two 10bp tandem
      repeats identified by using the Tandem Repeats Finder. U. thibetanus mupinensis
      mitochondrial genome shares high similarity with those of three other Ursidae: U.
      americanus (91.46%), U. arctos (89.25%) and U. maritimus (87.66%).

PMID- 17205109
TI  - Genetics of local adaptation in the laboratory: flowering time quantitative trait
      loci under geographic and seasonal conditions in Arabidopsis.
AB  - Flowering time in Arabidopsis thaliana is controlled by a large number of genes
      and various environmental factors, such as light and temperature. The objective
      of this study was to identify flowering time quantitative trait loci (QTL) under
      growth conditions simulating seasonal conditions from native geographic
      locations. Our growth chambers were set to simulate the spring conditions in
      Spain and Sweden, with appropriate changes in light color, intensity and day
      length, as well as temperature and relative humidity. Thus the Sweden-like spring
      conditions changed more dramatically compared to Spain-like spring conditions
      across the duration of our experiment. We have used these conditions to map QTL
      responsible for flowering time in the Kas-1/Col-gl1 recombinant inbred lines
      (RILs) across two replicate blocks. A linkage map from 96 RILs was established
      using 119 markers including 64 new SNPs markers. One major QTL, mapping to the
      FRIGIDA (FRI) locus, was detected on the top of chromosome 4 that showed
      significant gene x seasonal environment interactions. Three other minor QTL also
      were detected. One QTL mapping near FLOWERING LOCUS M (FLM) showed an epistatic
      interaction with the QTL at FRI. These QTLxenvironment and QTL x QTL interactions
      suggest that subtle ecologically relevant changes in light, temperature, and
      relative humidity are differentially felt by alleles controlling flowering time
      and may be responsible for adaptation to regional environments.

PMID- 17205110
TI  - An NF-kappaB and slug regulatory loop active in early vertebrate mesoderm.
AB  - BACKGROUND: In both Drosophila and the mouse, the zinc finger transcription
      factor Snail is required for mesoderm formation; its vertebrate paralog Slug
      (Snai2) appears to be required for neural crest formation in the chick and the
      clawed frog Xenopus laevis. Both Slug and Snail act to induce epithelial to
      mesenchymal transition (EMT) and to suppress apoptosis. METHODOLOGY & PRINCIPLE
      FINDINGS: Morpholino-based loss of function studies indicate that Slug is
      required for the normal expression of both mesodermal and neural crest markers in
      X. laevis. Both phenotypes are rescued by injection of RNA encoding the anti
      apoptotic protein Bcl-xL; Bcl-xL's effects are dependent upon IkappaB kinase
      mediated activation of the bipartite transcription factor NF-kappaB. NF-kappaB,
      in turn, directly up-regulates levels of Slug and Snail RNAs. Slug indirectly up
      regulates levels of RNAs encoding the NF-kappaB subunit proteins RelA, Rel2, and
      Rel3, and directly down-regulates levels of the pro-apopotic Caspase-9 RNA.
      CONCLUSIONS/SIGNIFICANCE: These studies reveal a Slug/Snail-NF-kappaB regulatory
      circuit, analogous to that present in the early Drosophila embryo, active during
      mesodermal formation in Xenopus. This is a regulatory interaction of significance
      both in development and in the course of inflammatory and metastatic disease.

PMID- 17205111
TI  - Biogenesis and dynamics of mitochondria during the cell cycle: significance of
      3'UTRs.
AB  - Nowadays, we are facing a renaissance of mitochondria in cancer biology. However,
      our knowledge of the basic cell biology and on the timing and mechanisms that
      control the biosynthesis of mitochondrial constituents during progression through
      the cell cycle of mammalian cells remain largely unknown. Herein, we document the
      in vivo changes on mitochondrial morphology and dynamics that accompany cellular
      mitosis, and illustrate the following key points of the biogenesis of
      mitochondria during progression of liver cells through the cycle: (i) the
      replication of nuclear and mitochondrial genomes is synchronized during cellular
      proliferation, (ii) the accretion of OXPHOS proteins is asynchronously regulated
      during proliferation being the synthesis of beta-F1-ATPase and Hsp60 carried out
      also at G2/M and, (iii) the biosynthesis of cardiolipin is achieved during the S
      phase, although full development of the mitochondrial membrane potential
      (DeltaPsim) is attained at G2/M. Furthermore, we demonstrate using reporter
      constructs that the mechanism regulating the accretion of beta-F1-ATPase during
      cellular proliferation is controlled at the level of mRNA translation by the
      3'UTR of the transcript. The 3'UTR-driven synthesis of the protein at G2/M is
      essential for conferring to the daughter cells the original phenotype of the
      parental cell. Our findings suggest that alterations on this process may promote
      deregulated beta-F1-ATPase expression in human cancer.

PMID- 17205112
TI  - Soluble TNF mediates the transition from pulmonary inflammation to fibrosis.
AB  - BACKGROUND: Fibrosis, the replacement of functional tissue with excessive fibrous
      tissue, can occur in all the main tissues and organ systems, resulting in various
      pathological disorders. Idiopathic Pulmonary Fibrosis is a prototype fibrotic
      disease involving abnormal wound healing in response to multiple sites of ongoing
      alveolar epithelial injury. METHODOLOGY/PRINCIPAL FINDINGS: To decipher the role
      of TNF and TNF-mediated inflammation in the development of fibrosis, we have
      utilized the bleomycin-induced animal model of Pulmonary Fibrosis and a series of
      genetically modified mice lacking components of TNF signaling. Transmembrane TNF
      expression is shown to be sufficient to elicit an inflammatory response, but
      inadequate for the transition to the fibrotic phase of the disease. Soluble TNF
      expression is shown to be crucial for lymphocyte recruitment, a prerequisite for
      TGF-b1 expression and the development of fibrotic lesions. Moreover, through a
      series of bone marrow transfers, the necessary TNF expression is shown to
      originate from the non-hematopoietic compartment further localized in apoptosing
      epithelial cells. CONCLUSIONS: These results suggest a primary detrimental role
      of soluble TNF in the pathologic cascade, separating it from the beneficial role
      of transmembrane TNF, and indicate the importance of assessing the efficacy of
      soluble TNF antagonists in the treatment of Idiopathic Pulmonary Fibrosis.

PMID- 17205113
TI  - To have or not to have a pet for better health?
AB  - BACKGROUND: Pet ownership is thought to have health benefits, but not all
      scientific explorations have been founded on proper applications of
      representative samples or statistically correct methodologies. Databanks have
      been too small for proper statistical analyses; or, instead of a random sample,
      participation has been voluntary. The direction of causality has been evaluated
      incorrectly or control of relevant factors noted deficient. This study examined
      the associations of pet ownership with perceived health and disease indicators by
      taking into account socio-demographic background factors together with health
      risk factors, including exercise. METHODOLOGY/PRINCIPAL FINDINGS: The present
      study used baseline data from the 15-year Health and Social Support Study (the
      HeSSup Study). The Finnish Population Register Centre was used to draw population
      based random samples stratified according to gender and four age groups (20-24,
      30-34, 40-44, and 50-54 years). A total of 21,101 working-aged Finns responded to
      the baseline survey questionnaire of the 15-year HeSSup Study in 1998. Ordinal
      and binary logistic regression was used to analyze the cross-sectional data. Pet
      ownership was associated with poor rather than good perceived health. BMI
      surfaced as the risk factor most strongly associated with pet ownership.
      CONCLUSIONS/SIGNIFICANCE: Pet owners set in their ways and getting older were
      found to have a slightly higher BMI than the rest. Additional research is needed
      for the testing of hypotheses involving effects of pet ownership with various
      health dimensions within population groups that are composed of different kinds
      of background characteristics.

PMID- 17205114
TI  - Unusually long palindromes are abundant in mitochondrial control regions of
      insects and nematodes.
AB  - BACKGROUND: Palindromes are known to be involved in a variety of biological
      processes. In the present investigation we carried out a comprehensive analysis
      of palindromes in the mitochondrial control regions (CRs) of several animal
      groups to study their frequency, distribution and architecture to gain insights
      into the origin of replication of mtDNA. METHODOLOGY/PRINCIPAL FINDINGS: Many
      species of Arthropoda, Nematoda, Mollusca and Annelida harbor palindromes and
      inverted repeats (IRs) in their CRs. Lower animals like cnidarians and higher
      animal groups like chordates are almost devoid of palindromes and IRs. The study
      revealed that palindrome occurrence is positively correlated with the AT content
      of CRs, and that IRs are likely to give rise to longer palindromes.
      CONCLUSIONS/SIGNIFICANCE: The present study attempts to explain possible reasons
      and gives in silico evidence for absence of palindromes and IRs from CR of
      vertebrate mtDNA and acquisition and retention of the same in insects. Study of
      CRs of different animal phyla uncovered unique architecture of this locus, be it
      high abundance of long palindromes and IRs in CRs of Insecta and Nematoda, or
      short IRs of 10-20 nucleotides with a spacer region of 12-14 bases in subphylum
      Chelicerata, or nearly complete of absence of any long palindromes and IRs in
      Vertebrata, Cnidaria and Echinodermata.

PMID- 17205115
TI  - The interplay between PolyQ and protein context delays aggregation by forming a
      reservoir of protofibrils.
AB  - Polyglutamine (polyQ) diseases are inherited neurodegenerative disorders caused
      by the expansion of CAG codon repeats, which code for polyQ in the corresponding
      gene products. These diseases are associated with the presence of amyloid-like
      protein aggregates, induced by polyQ expansion. It has been suggested that the
      soluble aggregates rather than the mature fibrillar aggregates are the toxic
      species, and that the aggregation properties of polyQ can be strongly modulated
      by the surrounding protein context. To assess the importance of the protein
      carrier in polyQ aggregation, we have studied the misfolding pathway and the
      kinetics of aggregation of polyQ of lengths above (Q41) and below (Q22) the
      pathological threshold fused to the well-characterized protein carrier
      glutathione S-transferase (GST). This protein, chosen as a model system, is per
      se able to misfold and aggregate irreversibly, thus mimicking the behaviour of
      domains of naturally occurring polyQ proteins. We prove that, while it is
      generally accepted that the aggregation kinetics of polyQ depend on its length
      and are faster for longer polyQ tracts, the presence of GST alters the polyQ
      aggregation pathway and reverses this trend. Aggregation occurs through formation
      of a reservoir of soluble intermediates whose populations and kinetic stabilities
      increase with polyQ length. Our results provide a new model that explains the
      toxicity of expanded polyQ proteins, in which the interplay between polyQ regions
      and other aggregation-prone domains plays a key role in determining the
      aggregation pathway.

PMID- 17205116
TI  - Increased nucleotide diversity with transient Y linkage in Drosophila americana.
AB  - Recombination shapes nucleotide variation within genomes. Patterns are thought to
      arise from the local recombination landscape, influencing the degree to which
      neutral variation experiences hitchhiking with selected variation. This study
      examines DNA polymorphism along Chromosome 4 (element B) of Drosophila americana
      to identify effects of hitchhiking arising as a consequence of Y-linked
      transmission. A centromeric fusion between the X and 4(th) chromosomes segregates
      in natural populations of D. americana. Frequency of the X-4 fusion exhibits a
      strong positive correlation with latitude, which has explicit consequences for
      unfused 4(th) chromosomes. Unfused Chromosome 4 exists as a non-recombining Y
      chromosome or as an autosome proportional to the frequency of the X-4 fusion.
      Furthermore, Y linkage along the unfused 4 is disrupted as a function of the rate
      of recombination with the centromere. Inter-population and intra-chromosomal
      patterns of nucleotide diversity were assayed using six regions distributed along
      unfused 4(th) chromosomes derived from populations with different frequencies of
      the X-4 fusion. No difference in overall level of nucleotide diversity was
      detected among populations, yet variation along the chromosome exhibits a
      distinct pattern in relation to the X-4 fusion. Sequence diversity is inflated at
      loci experiencing the strongest Y linkage. These findings are inconsistent with
      the expected reduction in nucleotide diversity resulting from hitchhiking due to
      background selection or selective sweeps. In contrast, excessive polymorphism is
      accruing in association with transient Y linkage, and furthermore, hitchhiking
      with sexually antagonistic alleles is potentially responsible.

PMID- 17205117
TI  - Towards alignment independent quantitative assessment of homology detection.
AB  - Identification of homologous proteins provides a basis for protein annotation.
      Sequence alignment tools reliably identify homologs sharing high sequence
      similarity. However, identification of homologs that share low sequence
      similarity remains a challenge. Lowering the cutoff value could enable the
      identification of diverged homologs, but also introduces numerous false hits.
      Methods are being continuously developed to minimize this problem. Estimation of
      the fraction of homologs in a set of protein alignments can help in the
      assessment and development of such methods, and provides the users with intuitive
      quantitative assessment of protein alignment results. Herein, we present a
      computational approach that estimates the amount of homologs in a set of protein
      pairs. The method requires a prevalent and detectable protein feature that is
      conserved between homologs. By analyzing the feature prevalence in a set of
      pairwise protein alignments, the method can estimate the number of homolog pairs
      in the set independently of the alignments' quality. Using the HomoloGene
      database as a standard of truth, we implemented this approach in a proteome-wide
      analysis. The results revealed that this approach, which is independent of the
      alignments themselves, works well for estimating the number of homologous
      proteins in a wide range of homology values. In summary, the presented method can
      accompany homology searches and method development, provides validation to search
      results, and allows tuning of tools and methods.

PMID- 17205118
TI  - Transcriptional changes common to human cocaine, cannabis and phencyclidine
      abuse.
AB  - A major goal of drug abuse research is to identify and understand drug-induced
      changes in brain function that are common to many or all drugs of abuse. As these
      may underlie drug dependence and addiction, the purpose of the present study was
      to examine if different drugs of abuse effect changes in gene expression that
      converge in common molecular pathways. Microarray analysis was employed to assay
      brain gene expression in postmortem anterior prefrontal cortex (aPFC) from 42
      human cocaine, cannabis and/or phencyclidine abuse cases and 30 control cases,
      which were characterized by toxicology and drug abuse history. Common
      transcriptional changes were demonstrated for a majority of drug abuse cases (N =
      34), representing a number of consistently changed functional classes: Calmodulin
      related transcripts (CALM1, CALM2, CAMK2B) were decreased, while transcripts
      related to cholesterol biosynthesis and trafficking (FDFT1, APOL2, SCARB1), and
      Golgi/endoplasmic reticulum (ER) functions (SEMA3B, GCC1) were all increased.
      Quantitative PCR validated decreases in calmodulin 2 (CALM2) mRNA and increases
      in apolipoprotein L, 2 (APOL2) and semaphorin 3B (SEMA3B) mRNA for individual
      cases. A comparison between control cases with and without cardiovascular disease
      and elevated body mass index indicated that these changes were not due to general
      cellular and metabolic stress, but appeared specific to the use of drugs.
      Therefore, humans who abused cocaine, cannabis and/or phencyclidine share a
      decrease in transcription of calmodulin-related genes and increased transcription
      related to lipid/cholesterol and Golgi/ER function. These changes represent
      common molecular features of drug abuse, which may underlie changes in synaptic
      function and plasticity that could have important ramifications for decision
      making capabilities in drug abusers.

PMID- 17205119
TI  - Detection of conjugation related type four secretion machinery in Aeromonas
      culicicola.
AB  - BACKGROUND: Aeromonas sp. can now be considered relatively common enteropathogens
      due to the increase of diseases in humans. Aeromonas culicicola is a gram
      negative rod-shaped bacterium isolated for the first time from the mosquito mid
      gut, but subsequently detected in other insects and waters also. Our previous
      study discovered that A. culicicola harbors three plasmids, which we designated
      as pAc3249A, pAc3249B and pAc3249C. We investigated and report here the existence
      and genetic organization of a Conjugal Type IV Secretion System (TFSS) in
      pAc3249A. METHODOLOGY/PRINCIPLE FINDING: The complete operon is 11,061 bp in
      length and has G+C content of 47.20% code for 12 ORFs. The gene order and
      orientation were similar to those found in other bacteria with some differences.
      We have designated this system as AcTra for Aeromonas culicicola transfer system.
      BLAST results of ORFs and phylogenetic analysis showed significant similarity
      towards the respective proteins of the IncI2 plasmid R721 of E. coli. Other
      bioinformatics studies have been performed to predict conserved motifs/domains,
      signal peptides, transmembrane helices, etc. of the ORFs.
      CONCLUSIONS/SIGNIFICANCE: BLAST results of ORFs and phylogenetic analysis showed
      significant similarity towards the respective proteins of the IncI2 plasmid R721
      of E. coli.

PMID- 17205120
TI  - MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia.
AB  - MicroRNAs (miRNAs) are a class of 20-24 nt non-coding RNAs that regulate gene
      expression primarily through post-transcriptional repression or mRNA degradation
      in a sequence-specific manner. The roles of miRNAs are just beginning to be
      understood, but the study of miRNA function has been limited by poor
      understanding of the general principles of gene regulation by miRNAs. Here we
      used CNE cells from a human nasopharyngeal carcinoma cell line as a cellular
      system to investigate miRNA-directed regulation of VEGF and other angiogenic
      factors under hypoxia, and to explore the principles of gene regulation by
      miRNAs. Through computational analysis, 96 miRNAs were predicted as putative
      regulators of VEGF. But when we analyzed the miRNA expression profile of CNE and
      four other VEGF-expressing cell lines, we found that only some of these miRNAs
      could be involved in VEGF regulation, and that VEGF may be regulated by different
      miRNAs that were differentially chosen from 96 putative regulatory miRNAs of VEGF
      in different cells. Some of these miRNAs also co-regulate other angiogenic
      factors (differential regulation and co-regulation principle). We also found that
      VEGF was regulated by multiple miRNAs using different combinations, including
      both coordinate and competitive interactions. The coordinate principle states
      that miRNAs with independent binding sites in a gene can produce coordinate
      action to increase the repressive effect of miRNAs on this gene. By contrast, the
      competitive principle states when multiple miRNAs compete with each other for a
      common binding site, or when a functional miRNA competes with a false positive
      miRNA for the same binding site, the repressive effects of miRNAs may be
      decreased. Through the competitive principle, false positive miRNAs, which cannot
      directly repress gene expression, can sometimes play a role in miRNA-mediated
      gene regulation. The competitive principle, differential regulation, multi-miRNA
      binding sites, and false positive miRNAs might be useful strategies in the
      avoidance of unwanted cross-action among genes targeted by miRNAs with multiple
      targets.

PMID- 17205121
TI  - Catechol-o-methyltransferase gene polymorphism modifies the effect of coffee
      intake on incidence of acute coronary events.
AB  - BACKGROUND: The role of coffee intake as a risk factor for coronary heart disease
      (CHD) has been debated for decades. We examined whether the relationship between
      coffee intake and incidence of CHD events is dependent on the metabolism of
      circulating catecholamines, as determined by functional polymorphism of the
      catechol-O-methyltransferase (COMT) gene. METHODOLOGY/PRINCIPAL FINDINGS: In a
      cohort of 773 men who were 42 to 60 years old and free of symptomatic CHD at
      baseline in 1984-89, 78 participants experienced an acute coronary event during
      an average follow-up of 13 years. In logistic regression adjusting for age,
      smoking, family history of CHD, vitamin C deficiency, blood pressure, plasma
      cholesterol concentration, and diabetes, the odds ratio (90% confidence interval)
      comparing heavy coffee drinkers with the low activity COMT genotype with those
      with the high activity or heterozygotic genotypes was 3.2 (1.2-8.4). Urinary
      adrenaline excretion increased with increasing coffee intake, being over two-fold
      in heavy drinkers compared with nondrinkers (p = 0.008 for trend).
      CONCLUSIONS/SIGNIFICANCE: Heavy coffee consumption increases the incidence of
      acute coronary events in men with low but not high COMT activity. Further studies
      are required to determine to which extent circulating catecholamines mediate the
      relationship between coffee intake and CHD.

PMID- 17205122
TI  - Swordtail fry attend to chemical and visual cues in detecting predators and
      conspecifics.
AB  - Predation pressure and energy requirements present particularly salient opposing
      selective pressures on young fish. Thus, fry are expected to possess
      sophisticated means of detecting predators and resources. Here we tested the
      hypotheses that fry of the swordtail fish Xiphophorus birchmanni use chemical and
      visual cues in detection of predators and conspecifics. To test these hypotheses
      we presented young (<7 day-old) fry with combinations of visual and chemical
      stimuli from adult conspecifics and predators. We found that exposure to predator
      odors resulted in shoal tightening similar to that observed when fry were
      presented with visual cues alone. In trials with conspecific stimuli, fry were
      particularly attracted to adult conspecifics when presented simultaneous visual
      and chemical stimuli compared to the visual stimulus alone. These results show
      that fry attend to the odors of adult conspecifics, whose presence in a
      particular area may signal the location of resources as well as an absence of
      predators. This is one of the first studies to show that such young fish use
      chemical and visual cues in predator detection and in interactions with
      conspecifics. Previous research in X. birchmanni has shown that anthropogenic
      alteration of the chemical environment disrupts intraspecific chemical
      communication among adults; we suggest that because fry use the same chemosensory
      pathways to detect predators and conspecifics, alteration of the chemical
      environment may critically disrupt predator and resource detection.

PMID- 17205123
TI  - Designer self-assembling peptide nanofiber scaffolds for adult mouse neural stem
      cell 3-dimensional cultures.
AB  - Biomedical researchers have become increasingly aware of the limitations of
      conventional 2-dimensional tissue cell culture systems, including coated Petri
      dishes, multi-well plates and slides, to fully address many critical issues in
      cell biology, cancer biology and neurobiology, such as the 3-D microenvironment,
      3-D gradient diffusion, 3-D cell migration and 3-D cell-cell contact
      interactions. In order to fully understand how cells behave in the 3-D body, it
      is important to develop a well-controlled 3-D cell culture system where every
      single ingredient is known. Here we report the development of a 3-D cell culture
      system using a designer peptide nanofiber scaffold with mouse adult neural stem
      cells. We attached several functional motifs, including cell adhesion,
      differentiation and bone marrow homing motifs, to a self-assembling peptide
      RADA16 (Ac-RADARADARADARADA-COHN2). These functionalized peptides undergo self
      assembly into a nanofiber structure similar to Matrigel. During cell culture, the
      cells were fully embedded in the 3-D environment of the scaffold. Two of the
      peptide scaffolds containing bone marrow homing motifs significantly enhanced the
      neural cell survival without extra soluble growth and neurotrophic factors to the
      routine cell culture media. In these designer scaffolds, the cell populations
      with beta-Tubulin(+), GFAP(+) and Nestin(+) markers are similar to those found in
      cell populations cultured on Matrigel. The gene expression profiling array
      experiments showed selective gene expression, possibly involved in neural stem
      cell adhesion and differentiation. Because the synthetic peptides are
      intrinsically pure and a number of desired function cellular motifs are easy to
      incorporate, these designer peptide nanofiber scaffolds provide a promising
      controlled 3-D culture system for diverse tissue cells, and are useful as well
      for general molecular and cell biology.

PMID- 17205124
TI  - Cooperation between engulfment receptors: the case of ABCA1 and MEGF10.
AB  - The engulfment of dying cells is a specialized form of phagocytosis that is
      extremely conserved across evolution. In the worm, it is genetically controlled
      by two parallel pathways, which are only partially reconstituted in mammals. We
      focused on the recapitulation of the CED-1 defined pathway in mammalian systems.
      We first explored and validated MEGF10, a novel receptor bearing striking
      structural similarities to CED-1, as a bona fide functional ortholog in mammals
      and hence progressed toward the analysis of molecular interactions along the
      corresponding pathway. We ascertained that, in a system of forced expression by
      transfection, MEGF10 function can be modulated by the ATP binding cassette
      transporter ABCA1, ortholog to CED-7. Indeed, the coexpression of either a
      functional or a mutant ABCA1 exerted a transdominant positive or negative
      modulation on the MEGF10-dependent engulfment. The combined use of biochemical
      and biophysical approaches indicated that this functional cooperation relies on
      the alternate association of these receptors with a common partner, endogenously
      expressed in our cell system. We provide the first working model structuring in
      mammals the CED-1 dependent pathway.

PMID- 17205125
TI  - Acceptance of anti-retroviral therapy among patients infected with HIV and
      tuberculosis in rural Malawi is low and associated with cost of transport.
AB  - BACKGROUND: A study was conducted among newly registered HIV-positive
      tuberculosis (TB) patients systematically offered anti-retroviral treatment (ART)
      in a district hospital in rural Malawi in order to a) determine the acceptance of
      ART b) conduct a geographic mapping of those placed on ART and c) examine the
      association between "cost of transport" and ART acceptance. METHODOLOGY/PRINCIPAL
      FINDINGS: A retrospective cross-sectional analysis was performed on routine
      program data for the period of February 2003 to July 2004. Standardized registers
      and patient cards were used to gather data. The place of residence was used to
      determine road distances to the Thyolo district hospital. Cost of transport from
      different parts of the district was based on the known cost for public transport
      to the road-stop closest to the patient's residence. Of 1,290 newly registered TB
      patients, 1,003(78%) underwent HIV-testing of whom 770 (77%) were HIV-positive.
      742 of these individuals (pulmonary TB = 607; extra-pulmonary TB = 135) were
      considered eligible for ART of whom only 101(13.6%) accepted ART. Cost of
      transport to the hospital ART site was significantly associated with ART
      acceptance and there was a linear trend in association between cost and ART
      acceptance (chi(2) for trend = 25.4, P<0.001). Individuals who had to pay 50
      Malawi Kwacha (1 United States Dollar = 100 Malawi Kwacha, MW) or less for a one
      way trip to the Thyolo hospital were four times more likely to accept ART than
      those who had to pay over 100 MW (Adjusted Odds ratio = 4.0, 95% confidence
      interval: 2.0-8.1, P<0.001). CONCLUSIONS/SIGNIFICANCE: ART acceptance among TB
      patients in a rural district in Malawi is low and associated with cost of
      transport to the centralized hospital based ART site. Decentralizing the ART
      offer from the hospital to health centers that are closer to home communities
      would be an essential step towards reducing the overall cost and burden of
      travel.

PMID- 17205126
TI  - Shaping leg muscles in Drosophila: role of ladybird, a conserved regulator of
      appendicular myogenesis.
AB  - Legs are locomotor appendages used by a variety of evolutionarily distant
      vertebrates and invertebrates. The primary biological leg function, locomotion,
      requires the formation of a specialised appendicular musculature. Here we report
      evidence that ladybird, an orthologue of the Lbx1 gene recognised as a hallmark
      of appendicular myogenesis in vertebrates, is expressed in leg myoblasts, and
      regulates the shape, ultrastructure and functional properties of leg muscles in
      Drosophila. Ladybird expression is progressively activated in myoblasts
      associated with the imaginal leg disc and precedes that of the founder cell
      marker dumbfounded. The RNAi-mediated attenuation of ladybird expression alters
      properties of developing myotubes, impairing their ability to grow and interact
      with the internal tendons and epithelial attachment sites. It also affects
      sarcomeric ultrastructure, resulting in reduced leg muscle performance and
      impaired mobility in surviving flies. The over-expression of ladybird also
      results in an abnormal pattern of dorsally located leg muscles, indicating
      different requirements for ladybird in dorsal versus ventral muscles. This
      differential effect is consistent with the higher level of Ladybird in ventrally
      located myoblasts and with positive ladybird regulation by extrinsic Wingless
      signalling from the ventral epithelium. In addition, ladybird expression
      correlates with that of FGF receptor Heartless and the read-out of FGF signalling
      downstream of FGF. FGF signals regulate the number of leg disc associated
      myoblasts and are able to accelerate myogenic differentiation by activating
      ladybird, leading to ectopic muscle fibre formation. A key role for ladybird in
      leg myogenesis is further supported by its capacity to repress vestigial and to
      down-regulate the vestigial-governed flight muscle developmental programme. Thus
      in Drosophila like in vertebrates, appendicular muscles develop from a
      specialised pool of myoblasts expressing ladybird/Lbx1. The ladybird/Lbx1 gene
      family appears as a part of an ancient genetic circuitry determining leg-specific
      properties of myoblasts and making an appendage adapted for locomotion.

PMID- 17205127
TI  - Natural variation in partial resistance to Pseudomonas syringae is controlled by
      two major QTLs in Arabidopsis thaliana.
AB  - BACKGROUND: Low-level, partial resistance is pre-eminent in natural populations,
      however, the mechanisms underlying this form of resistance are still poorly
      understood. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we used the
      model pathosystem Pseudomonas syringae pv. tomato DC3000 (Pst) - Arabidopsis
      thaliana to study the genetic basis of this form of resistance. Phenotypic
      analysis of a set of Arabidopsis accessions, based on evaluation of in planta
      pathogen growth revealed extensive quantitative variation for partial resistance
      to Pst. It allowed choosing a recombinant inbred line (RIL) population derived
      from a cross between the accessions Bayreuth and Shahdara for quantitative
      genetic analysis. Experiments performed under two different environmental
      conditions led to the detection of two major and two minor quantitative trait
      loci (QTLs) governing partial resistance to Pst and called PRP-Ps1 to PRP-Ps4.
      The two major QTLs, PRP-Ps1 and PRP-Ps2, were confirmed in near isogenic lines
      (NILs), following the heterogeneous inbred families (HIFs) strategy. Analysis of
      marker gene expression using these HIFs indicated a negative correlation between
      the induced amount of transcripts of SA-dependent genes PR1, ICS and PR5, and the
      in planta bacterial growth in the HIF segregating at PRP-Ps2 locus, suggesting an
      implication of PRP-Ps2 in the activation of SA dependent responses.
      CONCLUSIONS/SIGNIFICANCE: These results show that variation in partial resistance
      to Pst in Arabidopsis is governed by relatively few loci, and the validation of
      two major loci opens the way for their fine mapping and their cloning, which will
      improve our understanding of the molecular mechanisms underlying partial
      resistance.

PMID- 17205128
TI  - IL-7 up-regulates TNF-alpha-dependent osteoclastogenesis in patients affected by
      solid tumor.
AB  - BACKGROUND: Interleukin-7 (IL-7) is a potent regulator of lymphocyte development,
      which has also significant effects on bone; in fact it is a potent
      osteoclastogenic factor. Some human solid tumors produce high IL-7 levels,
      suggesting a potential IL-7 role on tumor development and progression.
      METHODOLOGY: We studied 50 male patients affected by solid tumors, and their
      blood samples were collected at tumor diagnosis. PBMCs were isolated and cultured
      with/without IL-7 to study its influence on osteoclastogenesis. Serum and cell
      culture supernatant IL-7 levels were measured by ELISA. The quantitative analysis
      of IL-7 expression on T and B cells was performed by Real-Time PCR. PRINCIPAL
      FINDINGS: Serum IL-7 levels were highest in osteolytic cancer patients, followed
      by cancer patients without bone lesions, and then healthy controls. We showed the
      IL-7 production in PBMC cultures and particularly in monocyte and B cell co
      cultures. A quantitative analysis of IL-7 expression in T and B cells confirmed
      that B cells had a high IL-7 expression. In all cell culture conditions, IL-7
      significantly increased osteoclastogenesis and an anti-IL-7 antibody inhibited
      it. We demonstrated that IL-7 supports OC formation by inducing the TNF-alpha
      production and low RANKL levels, which synergize in promoting osteoclastogenesis.
      CONCLUSIONS: We demonstrated the presence of high serum IL-7 levels in patients
      with bone metastasis, suggesting the use of serum IL-7 level as a clinical marker
      of disease progression and of bone involvement. Moreover, we showed the
      capability of IL-7 to stimulate spontaneous osteoclastogenesis of bone metastatic
      patients and to induce osteoclastogenesis in cancer patients without bone
      involvement. These findings add further details to the disclosure of the
      mechanisms controlling bone metastasis in solid tumors.

PMID- 17205129
TI  - Heterozygote advantage for fecundity.
AB  - Heterozygote advantage, or overdominance, remains a popular and persuasive
      explanation for the maintenance of genetic variation in natural populations in
      the face of selection. However, despite being first proposed more than 80 years
      ago, there remain few examples that fit the criteria for heterozygote advantage,
      all of which are associated with disease resistance and are maintained only in
      the presence of disease or other gene-by-environment interaction. Here we report
      five new examples of heterozygote advantage, based around polymorphisms in the
      BMP15 and GDF9 genes that affect female fecundity in domesticated sheep and are
      not reliant on disease for their maintenance. Five separate mutations in these
      members of the transforming growth factor beta (TGFbeta) superfamily give
      phenotypes with fitness differentials characteristic of heterozygous advantage.
      In each case, one copy of the mutant allele increases ovulation rate, and
      ultimately litter size per ewe lambing, relative to the wildtype. However,
      homozygous ewes inheriting mutant alleles from both parents have impaired oocyte
      development and maturation, which results in small undeveloped ovaries and
      infertility. Using data collected over many years on ovulation rates, litter
      size, and lambing rates, we have calculated the equilibrium solution for each of
      these polymorphisms using standard population genetic theory. The predicted
      equilibrium frequencies obtained for these mutant alleles range from 0.11 to
      0.23, which are amongst the highest yet reported for a polymorphism maintained by
      heterozygote advantage. These are amongst the most frequent and compelling
      examples of heterozygote advantage yet described and the first documented
      examples of heterozygote advantage that are not reliant on a disease interaction
      for their maintenance.

PMID- 17205130
TI  - Docking of secretory vesicles is syntaxin dependent.
AB  - Secretory vesicles dock at the plasma membrane before they undergo fusion.
      Molecular docking mechanisms are poorly defined but believed to be independent of
      SNARE proteins. Here, we challenged this hypothesis by acute deletion of the
      target SNARE, syntaxin, in vertebrate neurons and neuroendocrine cells. Deletion
      resulted in fusion arrest in both systems. No docking defects were observed in
      synapses, in line with previous observations. However, a drastic reduction in
      morphologically docked secretory vesicles was observed in chromaffin cells.
      Syntaxin-deficient chromaffin cells showed a small reduction in total and plasma
      membrane staining for the docking factor Munc18-1, which appears insufficient to
      explain the drastic reduction in docking. The sub-membrane cortical actin network
      was unaffected by syntaxin deletion. These observations expose a docking role for
      syntaxin in the neuroendocrine system. Additional layers of regulation may have
      evolved to make syntaxin redundant for docking in highly specialized systems like
      synaptic active zones.

PMID- 17205131
TI  - Gender differences in publication output: towards an unbiased metric of research
      performance.
AB  - We examined the publication records of a cohort of 168 life scientists in the
      field of ecology and evolutionary biology to assess gender differences in
      research performance. Clear discrepancies in publication rate between men and
      women appear very early in their careers and this has consequences for the
      subsequent citation of their work. We show that a recently proposed index
      designed to rank scientists fairly is in fact strongly biased against female
      researchers, and advocate a modified index to assess men and women on a more
      equitable basis.

PMID- 17205132
TI  - A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell
      proliferation.
AB  - Cyclin D1 regulates G1 progression. Its transcriptional regulation is well
      understood. However, the mechanism underlying cyclin D1 ubiquitination and its
      subsequent degradation is not yet clear. We report that cyclin D1 undergoes
      increased degradation in the cytoplasm during S phase in a variety of cancer
      cells. This is mediated by phosphorylation at Thr286 through the activity of the
      Ras/Raf/MEK/ERK cascade and the F-box protein FBXW8, which is an E3 ligase. The
      majority of FBXW8 is expressed in the cytoplasm during G1 and S phase. In
      contrast, cyclin D1 accumulates in the nucleus during G1 phase and exits into the
      cytoplasm in S phase. Increased cyclin D1 degradation is linked to association
      with FBXW8 in the cytoplasm, and enhanced phosphorylation of cyclin D1 through
      sustained ERK1/2 signaling. Depletion of FBXW8 caused a significant accumulation
      of cyclin D1, as well as sequestration of CDK1 in the cytoplasm. This resulted in
      a severe reduction of cell proliferation. These effects could be rescued by
      constitutive nuclear expression of cyclin D1-T286A. Thus, FBXW8 plays an
      essential role in cancer cell proliferation through proteolysis of cyclin D1. It
      may present new opportunities to develop therapies targeting destruction of
      cyclin D1 or its regulator E3 ligase selectively.

PMID- 17205133
TI  - CD4+CD25+FOXP3+ regulatory T cells suppress anti-tumor immune responses in
      patients with colorectal cancer.
AB  - BACKGROUND: A wealth of evidence obtained using mouse models indicates that
      CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) maintain peripheral tolerance to
      self-antigens and also inhibit anti-tumor immune responses. To date there is
      limited information about CD4(+) T cell responses in patients with colorectal
      cancer (CRC). We set out to measure T cell responses to a tumor-associated
      antigen and examine whether Treg impinge on those anti-tumor immune responses in
      CRC patients. METHODOLOGY AND PRINCIPAL FINDINGS: Treg were identified and
      characterized as CD4(+)CD25(+)FOXP3(+) using flow cytometry. An increased
      frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph
      nodes of patients with colorectal cancer (CRC) compared with either healthy
      controls or patients with inflammatory bowel disease (IBD). Depletion of Treg
      from peripheral blood mononuclear cells (PBMC) of CRC patients unmasked CD4(+) T
      cell responses, as observed by IFNgamma release, to the tumor associated antigen
      5T4, whereas no effect was observed in a healthy age-matched control group.
      CONCLUSIONS/SIGNIFICANCE: Collectively, these data demonstrate that Treg capable
      of inhibiting tumor associated antigen-specific immune responses are enriched in
      patients with CRC. These results support a rationale for manipulating Treg to
      enhance cancer immunotherapy.

PMID- 17205134
TI  - Comparative toxicity of fumigants and a phosphine synergist using a novel
      containment chamber for the safe generation of concentrated phosphine gas.
AB  - BACKGROUND: With the phasing out of ozone-depleting substances in accordance with
      the United Nations Montreal Protocol, phosphine remains as the only economically
      viable fumigant for widespread use. However the development of high-level
      resistance in several pest insects threatens the future usage of phosphine; yet
      research into phosphine resistance mechanisms has been limited due to the
      potential for human poisoning in enclosed laboratory environments. PRINCIPAL
      FINDINGS: Here we describe a custom-designed chamber for safely containing
      phosphine gas generated from aluminium phosphide tablets. In an improvement on
      previous generation systems, this chamber can be completely sealed to control the
      escape of phosphine. The device has been utilised in a screening program with C.
      elegans that has identified a phosphine synergist, and quantified the efficacy of
      a new fumigant against that of phosphine. The phosphine-induced mortality at 20
      degrees C has been determined with an LC(50) of 732 ppm. This result was
      contrasted with the efficacy of a potential new botanical pesticide dimethyl
      disulphide, which for a 24 hour exposure at 20 degrees C is 600 times more potent
      than phosphine (LC(50) 1.24 ppm). We also found that co-administration of the
      glutathione depletor diethyl maleate (DEM) with a sublethal dose of phosphine (70
      ppm, <LC(5)), results in a doubling of mortality in C. elegans relative to DEM
      alone. CONCLUSIONS: The prohibitive danger associated with the generation,
      containment, and use of phosphine in a laboratory environment has now been
      substantially reduced by the implementation of our novel gas generation chamber.
      We have also identified a novel phosphine synergist, the glutathione depletor
      DEM, suggesting an effective pathway to be targeted in future synergist research;
      as well as quantifying the efficacy of a potential alternative to phosphine,
      dimethyl disulphide.

PMID- 17205136
TI  - A predator from East Africa that chooses malaria vectors as preferred prey.
AB  - BACKGROUND: All vectors of human malaria, a disease responsible for more than one
      million deaths per year, are female mosquitoes from the genus Anopheles. Evarcha
      culicivora is an East African jumping spider (Salticidae) that feeds indirectly
      on vertebrate blood by selecting blood-carrying female mosquitoes as preferred
      prey. METHODOLOGY/PRINCIPAL FINDINGS: By testing with motionless lures made from
      mounting dead insects in lifelike posture on cork discs, we show that E.
      culicivora selects Anopheles mosquitoes in preference to other mosquitoes and
      that this predator can identify Anopheles by static appearance alone. Tests using
      active (grooming) virtual mosquitoes rendered in 3-D animation show that
      Anopheles' characteristic resting posture is an important prey-choice cue for E.
      culicivora. Expression of the spider's preference for Anopheles varies with the
      spider's size, varies with its prior feeding condition and is independent of the
      spider gaining a blood meal. CONCLUSIONS/SIGNIFICANCE: This is the first
      experimental study to show that a predator of any type actively chooses Anopheles
      as preferred prey, suggesting that specialized predators having a role in the
      biological control of disease vectors is a realistic possibility.

PMID- 17205135
TI  - Rho kinase's role in myosin recruitment to the equatorial cortex of mitotic
      Drosophila S2 cells is for myosin regulatory light chain phosphorylation.
AB  - BACKGROUND: Myosin II recruitment to the equatorial cortex is one of the earliest
      events in establishment of the cytokinetic contractile ring. In Drosophila S2
      cells, we previously showed that myosin II is recruited to the furrow
      independently of F-actin, and that Rho1 and Rok are essential for this
      recruitment [1]. Rok phosphorylates several cellular proteins, including the
      myosin regulatory light chain (RLC). METHODOLOGY/PRINCIPAL FINDINGS: Here we
      express phosphorylation state mimic constructs of the RLC in S2 cells to examine
      the role of RLC phosphorylation involving Rok in the localization of myosin.
      Phosphorylation of the RLC is required for myosin localization to the equatorial
      cortex during mitosis, and the essential role of Rok in this localization and for
      cytokinesis is to maintain phosphorylation of the RLC. The ability to regulate
      the RLC phosphorylation state spatio-temporally is not essential for the myosin
      localization. Furthermore, the essential role of Citron in cytokinesis is not
      phosphorylation of the RLC. CONCLUSIONS/SIGNIFICANCE: We conclude that the Rho1
      pathway leading to myosin localization to the future cytokinetic furrow is
      relatively straightforward, where only Rok is needed, and it is only needed to
      maintain phosphorylation of the myosin RLC.

PMID- 17205137
TI  - The sound generated by mid-ocean ridge black smoker hydrothermal vents.
AB  - Hydrothermal flow through seafloor black smoker vents is typically turbulent and
      vigorous, with speeds often exceeding 1 m/s. Although theory predicts that these
      flows will generate sound, the prevailing view has been that black smokers are
      essentially silent. Here we present the first unambiguous field recordings
      showing that these vents radiate significant acoustic energy. The sounds contain
      a broadband component and narrowband tones which are indicative of resonance. The
      amplitude of the broadband component shows tidal modulation which is indicative
      of discharge rate variations related to the mechanics of tidal loading. Vent
      sounds will provide researchers with new ways to study flow through sulfide
      structures, and may provide some local organisms with behavioral or navigational
      cues.

PMID- 17205138
TI  - Maf1, a new player in the regulation of human RNA polymerase III transcription.
AB  - BACKGROUND: Human RNA polymerase III (pol III) transcription is regulated by
      several factors, including the tumor suppressors P53 and Rb, and the proto
      oncogene c-Myc. In yeast, which lacks these proteins, a central regulator of pol
      III transcription, called Maf1, has been described. Maf1 is required for
      repression of pol III transcription in response to several signal transduction
      pathways and is broadly conserved in eukaryotes. METHODOLOGY/PRINCIPAL FINDINGS:
      We show that human endogenous Maf1 can be co-immunoprecipitated with pol III and
      associates in vitro with two pol III subunits, the largest subunit RPC1 and the
      alpha-like subunit RPAC2. Maf1 represses pol III transcription in vitro and in
      vivo and is required for maximal pol III repression after exposure to MMS or
      rapamycin, treatments that both lead to Maf1 dephosphorylation.
      CONCLUSIONS/SIGNIFICANCE: These data suggest that Maf1 is a major regulator of
      pol III transcription in human cells.

PMID- 17205139
TI  - DNA encoding an HIV-1 Gag/human lysosome-associated membrane protein-1 chimera
      elicits a broad cellular and humoral immune response in Rhesus macaques.
AB  - Previous studies of HIV-1 p55Gag immunization of mice have demonstrated the
      usefulness of targeting antigens to the cellular compartment containing the major
      histocompatibility complex type II (MHC II) complex molecules by use of a DNA
      antigen formulation encoding Gag as a chimera with the mouse lysosome-associated
      membrane protein (mLAMP/gag). In the present study, we have analyzed the
      magnitude and breadth of Gag-specific T-lymphocyte and antibody responses
      elicited in Rhesus macaques after immunization with DNA encoding a human LAMP/gag
      (hLAMP/gag) chimera. ELISPOT analyses indicated that the average Gag-specific IFN
      gamma response elicited by the hLAMP/gag chimera was detectable after only two or
      three naked DNA immunizations in all five immunized macaques and reached an
      average of 1000 spot-forming cells (SFC)/10(6) PBMCs. High IFN-gamma ELISPOT
      responses were detected in CD8(+)-depleted cells, indicating that CD4(+) T-cells
      play a major role in these responses. The T-cell responses of four of the
      macaques were also tested by use of ELISPOT to 12 overlapping 15-amino acids (aa)
      peptide pools containing ten peptides each, encompassing the complete Gag protein
      sequence. The two Mamu 08 immunized macaques responded to eight and twelve of the
      pools, the Mamu B01 to six, and the other macaque to five pools indicating that
      the hLAMP/gag DNA antigen formulation elicits a broad T-cell response against
      Gag. Additionally, there was a strong HIV-1-specific IgG response. The IgG
      antibody titers increased after each DNA injection, indicating a strong amnestic
      B-cell response, and were highly elevated in all the macaques after three
      immunizations. Moreover, the serum of each macaque recognized 13 of the 49
      peptides of a 20-aa peptide library covering the complete Gag amino acid
      sequence. In addition, HIV-1-specific IgA antibodies were present in the plasma
      and external secretions, including nasal washes. These data support the findings
      of increased immunogenicity of genetic vaccines encoded as LAMP chimeras,
      including the response to DNA vaccines by non-human primates.

PMID- 17205140
TI  - Analysis of in-vivo LacR-mediated gene repression based on the mechanics of DNA
      looping.
AB  - Interactions of E. coli lac repressor (LacR) with a pair of operator sites on the
      same DNA molecule can lead to the formation of looped nucleoprotein complexes
      both in vitro and in vivo. As a major paradigm for loop-mediated gene regulation,
      parameters such as operator affinity and spacing, repressor concentration, and
      DNA bending induced by specific or non-specific DNA-binding proteins (e.g., HU),
      have been examined extensively. However, a complete and rigorous model that
      integrates all of these aspects in a systematic and quantitative treatment of
      experimental data has not been available. Applying our recent statistical
      mechanical theory for DNA looping, we calculated repression as a function of
      operator spacing (58-156 bp) from first principles and obtained excellent
      agreement with independent sets of in-vivo data. The results suggest that a
      linear extended, as opposed to a closed v-shaped, LacR conformation is the
      dominant form of the tetramer in vivo. Moreover, loop-mediated repression in wild
      type E. coli strains is facilitated by decreased DNA rigidity and high levels of
      flexibility in the LacR tetramer. In contrast, repression data for strains
      lacking HU gave a near-normal value of the DNA persistence length. These findings
      underscore the importance of both protein conformation and elasticity in the
      formation of small DNA loops widely observed in vivo, and demonstrate the utility
      of quantitatively analyzing gene regulation based on the mechanics of
      nucleoprotein complexes.

PMID- 17205141
TI  - Stimulus dependence of barrel cortex directional selectivity.
AB  - Neurons throughout the rat vibrissa somatosensory pathway are sensitive to the
      angular direction of whisker movement. Could this sensitivity help rats
      discriminate stimuli? Here we use a simple computational model of cortical
      neurons to analyze the robustness of directional selectivity. In the model,
      directional preference emerges from tuning of synaptic conductance amplitude and
      latency, as in recent experimental findings. We find that directional selectivity
      during stimulation with random deflection sequences is strongly dependent on the
      mean deflection frequency: Selectivity is weakened at high frequencies even when
      each individual deflection evokes strong directional tuning. This variability of
      directional selectivity is due to generic properties of synaptic integration by
      the neuronal membrane, and is therefore likely to hold under very general
      physiological conditions. Our results suggest that directional selectivity
      depends on stimulus context. It may participate in tasks involving brief whisker
      contact, such as detection of object position, but is likely to be weakened in
      tasks involving sustained whisker exploration (e.g., texture discrimination).

PMID- 17205143
TI  - Gallbladder carcinoma surgical therapy. An overview.

PMID- 17205142
TI  - NMDA and dopamine converge on the NMDA-receptor to induce ERK activation and
      synaptic depression in mature hippocampus.
AB  - The formation of enduring internal representation of sensory information demands,
      in many cases, convergence in time and space of two different stimuli. The first
      conveys the sensory input, mediated via fast neurotransmission. The second
      conveys the meaning of the input, hypothesized to be mediated via slow
      neurotransmission. We tested the biochemical conditions and feasibility for fast
      (NMDA) and slow (dopamine) neurotransmission to converge on the Mitogen Activated
      Protein Kinase signaling pathways, crucial in several forms of synaptic
      plasticity, and recorded its effects upon synaptic transmission. We detected
      differing kinetics of ERK2 activation and synaptic strength changes in the CA1
      for low and high doses of neurotransmitters in hippocampal slices. Moreover, when
      weak fast and slow inputs are given together, they converge on ERK2, but not on
      p38 or JNK, and induce strong short-term synaptic depression. Surprisingly,
      pharmacological analysis revealed that a probable site of such convergence is the
      NMDA receptor itself, suggesting it serves as a detector and integrator of fast
      and slow neurotransmission in the mature mammalian brain, as revealed by ERK2
      activation and synaptic function.

PMID- 17205144
TI  - The effect of valsartan, an angiotensin II receptor antagonist, on portal and
      systemic hemodynamics and on renal function in liver cirrhosis.
AB  - AIM: The aim of the study was to assess the effects of valsartan, a new
      generation angiotensin II receptor antagonist, on portal and systemic
      hemodynamics and on renal function in cirrhosis. METHODS: Eighty patients with
      cirrhosis and portal hypertension were divided in two groups as follows: group I 
      40 patients who received valsartan (Diovan) 80 mg /day for 7 days and group II -
      40 patients who received placebo. All the patients had hemodynamic, endocrine and
      renal parameters measured on day 0 and 7. The following were assessed: creatinine
      clearance, lithium clearance, plasma renin activity, concentration of plasma
      aldosteron and sodium homeostasis. Hemodynamic effects were assessed
      sonographically by portal flow volume and velocity evaluation, and mean arterial
      blood pressure. RESULTS: Valsartan increased the portal blood flow and the portal
      velocity (p < 0.01). These changes occurred without any significant changes in
      blood pressure and renal function or the glomerular filtration rate, compared
      with controls (p > 0.05). Valsartan also reduced the concentration of plasma
      aldosteron (p < 0.01) and increased the urinary sodium excretion (p < 0.001).
      CONCLUSION: A one week treatment with valsartan in cirrhotic patients with portal
      hypertension determines an increase in natriuresis, which could be regarded as
      beneficial and changes in the portal hemodynamics which might be speculated to
      represent a reduction of portal resistance.

PMID- 17205145
TI  - Echo-Doppler measurements of portal vein and hepatic artery in asymptomatic
      patients with hepatitis B virus and healthy adults.
AB  - BACKGROUND AND AIM: The aim of this prospective study was to determine the range
      of various hemodynamic parameters of portal vein and hepatic artery with echo
      Doppler imaging in asymptomatic carriers of hepatitis B virus (HBV) and healthy
      adults. METHODS: One hundred and twenty two healthy adults and fifty-three
      asymptomatic patients with chronic HBV formed two groups. All participants
      underwent color Doppler imaging of the portal vein and hepatic artery. A single
      operator performed all echo-Doppler measurements. The examination protocol
      included measurements of portal vein and hepatic artery diameter (d), blood flow
      (BF), time averaged velocity (TAV) and calculation of Doppler Perfusion Index
      (DPI) of liver. RESULTS: Asymptomatic HBV carriers showed a statistically
      significant decrease in portal vein TAV (12.8 +/- 6.1 vs 17.5 +/- 8.8), an
      increase in portal vein BF (411.38 +/- 211.31 vs 327.55 +/- 188.77) and decrease
      in DPI (0.18 +/- 0.14 vs 0.28 +/- 0.15). CONCLUSIONS: Echo-Doppler measurements
      of portal vein and hepatic artery can detect significant hemodynamic changes in
      asymptomatic HBV carriers.

PMID- 17205146
TI  - NAT2 gene polymorphism and sporadic colorectal cancer. Prevalence, tumor stage
      and prognosis. A preliminary study in 70 patients.
AB  - AIM: Theoretically, individuals with a NAT2 rapid acetylator genotype are exposed
      to a higher risk of developing colorectal cancer. We attempted to study this
      relationship. MATERIAL AND METHODS: We evaluated a group of 70 patients with
      sporadic colorectal cancer and 40 controls. We calculated the relative risk for
      patients homozygous for the normal allele NAT2*5C, NAT2*5A, NAT2*6B, NAT2*7B, for
      heterozygous patients and for patients homozygous for the mutant allele. RESULTS:
      We found an increased risk for patients with a rapid acetylator genotype to
      develop colorectal cancer. Rapid acetylators, homozygous negative or heterozygous
      for the NAT2*5C, NAT2*5A and NAT2*6B mutations have an increased risk of
      colorectal cancer compared to homozygous positive patients.The analysis of the
      NAT2*5C genotype shows that the majority of the cases are at stage pT3 for rapid
      acetylators, 41 cases (74.54%), compared to slow acetylators, where the majority
      of cases are at stage pT4, 10 cases (66.66%) (p<0.05). The genotype with a rapid
      acetylator phenotype of the NAT2*5C, NAT2*5A and NAT2*7B variants was most
      frequently associated with Dukes stage B. The NAT2*5C, NAT2*5A and NAT2*7B gene
      variants with a slow acetylator pheno-type were most frequently associated with
      Dukes stage C. CONCLUSIONS: Rapid acetylators, homozygous negative or
      heterozygous for the NAT2*5C, NAT2*5A and NAT2*6B mutations have a higher risk of
      colorectal cancer compared to positive homozygotes. Rapid acetylators have
      earlier stages of colorectal cancer and a better prognosis than slow acetylators,
      who are diagnosed in more advanced stages.

PMID- 17205147
TI  - Pattern of relapses in Iranian patients with ulcerative colitis. A prospective
      study.
AB  - BACKGROUND: The pattern of relapses in patients with ulcerative colitis (UC) has
      a significant role in taking decisions about the therapy and the follow up of
      patients. This study is designed to find out the pattern, time and severity of
      relapses in Iranian patients with UC. METHOD: From 1991 to 2003, a period of 13
      years, the pattern of relapses in 163 patients with UC who had been admitted to a
      private referral gastroenterology clinic in Iran were evaluated. RESULTS: 163
      patients (58.3% female, 41.7% male) were included, aged from 17 to 74 years with
      mean age of 38.9 +/- 12.3 years. Mean follow up time was 52.7 +/- 41.4 months
      (ranges 12 and 155 months). Mean relapse chance was 0.028 +/- 0.036 for each
      patient in every month (ranges 0-0.21). The mean time from the initial attack to
      the first relapse was 23.8 +/- 22.5 months, which was not the same in patients
      with different primary disease severity (p = 0.03). CONCLUSION: The time and
      severity of the relapses relate to the severity of UC. Iranian patients have a
      milder course of the disease.

PMID- 17205148
TI  - Feasibility of day care surgery in proctology.
AB  - BACKGROUND: Proctological surgery is being carried out increasingly on an
      outpatient basis. The reasons for this are safe anesthetic procedures, short
      operation times and low complication rates. This study is a retrospective
      analysis of complication rates, symptom recurrence and long-term results
      according to outpatient proctologic surgery practiced in our hospital in the last
      10 years. MATERIAL AND METHOD: A total of 2840 patients were operated and
      followed up. The procedures included hemorrhoidectomy, anal fistulotomy,
      sphincterotomy, and removal of rectal polyps, pilonidal sinotomy and anal
      stricturotomy. Procedures were performed either under short-term general
      anesthesia or regional block. RESULTS: Mean hospital stay was 7.3 hours (range 4
      21 hours). The overall complication rate was 2.5%, which included bleeding,
      urinary retention, infection, continence disturbance and recurrence. CONCLUSION:
      Outpatient proctological surgery can be safely performed with a low recurrence
      and complication rate while offering a high level of patient acceptance and
      satisfaction. However, an appropriate diagnosis of the disease, proper selection
      of the patients with respect to their suitability for surgery and a round-the
      clock availability of patient communication with the nursing staff are a must for
      the successful outcome of the procedure.

PMID- 17205149
TI  - The role of cytokines in non-alcoholic steatohepatitis. A review.
AB  - The pathogenesis of NASH is being unraveled by studies of animal models and
      humans with this disorder. The necro-inflammatory component of NASH appears to be
      modulated by interactions among various factors (for example cytokines, hormones,
      neurotransmitters) that regulate the biological activity of TNF- and other
      proinflammatory (Th-1) cytokines. Hepatic necroinflammation is necessary, but not
      sufficient, for progression to cirrhosis. Factors such as leptin inducible
      factors (for example, noradrenaline), that regulate the activity of profibrogenic
      cytokines, such as IL-10 and TGF-beta, dictate the extent of fibrosis that occurs
      during liver injury. A better understanding of how these and other soluble and
      cell associated factors regulate the phenotypes of different types of liver cells
      should help us to develop rationale treatments for NASH and other disorders in
      the metabolic syndrome.

PMID- 17205150
TI  - Does capsule endoscopy recognise gastric antral vascular ectasia more frequently
      than conventional endoscopy?
AB  - BACKGROUND: Gastric antral vascular ectasia (GAVE) is a rare cause of obscure
      gastrointestinal bleeding which can be difficult to recognise endoscopically.
      Capsule endoscopy is primarily designed to image the small bowel, but may
      identify gastric and colonic lesions. There have been few reported cases of GAVE
      diagnosed by capsule endoscopy in the literature. OBJECTIVE: Our aim was to
      assess the frequency of GAVE in patients with obscure gastrointestinal bleeding
      referred for capsule endoscopy. DESIGN: Case series. SETTING: This study was
      conducted in a tertiary referral hospital. PATIENTS. This study comprised 128
      consecutive patients with obscure gastrointestinal bleeding. INTERVENTIONS: All
      patients underwent capsule endoscopy. RESULTS. Six patients were diagnosed with
      GAVE on the basis of the capsule endoscopy findings (4.7%, five female, median
      age 71.5 years). All patients had previously had numerous gastrointestinal
      investigations prior to capsule endoscopy. Five patients to date have been
      treated with argon plasma coagulation of their vascular lesions. This has
      resulted in stabilisation of their haemoglobin and cessation of blood
      transfusions in 4/5 cases with an average follow up period of 15 months.
      CONCLUSIONS: GAVE is commonly missed at gastroscopy and accounted for 4.7% of
      patients referred for capsule endoscopy with obscure gastrointestinal bleeding
      (in our series). This case series represents the largest number of GAVE
      recognised by capsule endoscopy. In the presence of any of the reported
      risk/associated factors for GAVE the gastroenterologist interpreting the capsule
      images should have a high index of suspicion.

PMID- 17205151
TI  - Treatment with infliximab in a patient with ankylosing spondylitis and Crohn's
      disease.
AB  - The association of Crohn's disease and ankylosing spondylitis is described in up
      to 30% of cases. Treatment of both conditions is not an easy task. We present the
      case of a 53 year old woman, diagnosed with colonic Crohn's disease and
      ankylosing spondilitis, treated initially with increasing doses of sulphasalazine
      and moderate dose of corticosteroids, with the persistence of severe
      gastrointestinal and articular symptoms. She underwent therapy with tumor
      necrosis factor alpha (TNFalpha) inhibitor infliximab, with a spectacular
      improvement of symptoms, signs and quality of life.

PMID- 17205152
TI  - Primary hydatid disease in a retroplaced gallbladder.
AB  - A 60-year-old man with abdominal distension, fever, vomiting and pain on the
      right upper quadrant of the abdomen was admitted to our hospital. US revealed a
      well circumscribed lesion of mixed echogenicity. CT revealed hypoplasia of the
      right liver lobe, and a cystic mass with solid components replacing a retroplaced
      gallbladder. On T1-weighted MR images the lesion had low signal intensity and
      presented mild peripheral post-contrast enhancement, while on T2-weighted images
      the periphery was of moderately high signal intensity and the centre of fluid
      like, high signal intensity. Adjacent liver parenchyma had relatively high signal
      intensity on T2-weighted images. The patient underwent exploratory laparotomy,
      and a hydatid cyst of the gallbladder that was inflamed was evidenced.

PMID- 17205153
TI  - Migrated biliary stent predisposing to fatal ERCP-related perforation of the
      duodenum.
AB  - ERCP may be associated with very serious and even fatal complications. Internal
      drainage with endoscopical prostheses has been used as a palliative treatment for
      malignant bile duct obstruction. We report a rare case of subcutaneous emphysema
      with a fatal outcome. The emphysema resulted from a perforation of a duodenal
      ulcer during ERCP due to a migrated biliary stent that had been previously
      endoscopically placed.

PMID- 17205154
TI  - The prevention of an expected hepatic flare in HBe negative patients after
      lamivudine discontinuation.
AB  - The treatment with lamivudine leads to drug resistant mutations in 19 to 70%
      cases after 1- and 5-year therapy, respectively, associated with the risk of
      severe rebound of liver disease with alaninaminotransferase flare. In this
      situation, adefovir should be added, but this drug is not available in every
      country. We report three cases where we avoided the expected hepatic flare-ups by
      using IFN and isoprinosine. Based on this empirical experience, we suggest that
      the new drug has to be administered one month before discontinuation of
      lamivudine. Prospective trials are mandatory.

PMID- 17205155
TI  - CT and MRI of acquired portal venous system anomalies.
AB  - In this educational presentation, we offer an overview of acquired anomalies of
      the portal venous system explored by biphasic helical CT and MRI. Portosystemic
      collateral vessels, cavernous transformation of the portal vein, intrahepatic
      vascular shunts, aneurysms of the portal venous system, thrombosis of the portal
      venous system, and gas in the portal venous system will be discussed. For liver
      surgery and interventional procedures it is necessary to have a correct mapping
      of normal anatomy, variants, and different pathologies involving the portal
      venous system.

PMID- 17205156
TI  - E-publishing develops rapidly in Romania: the experience of the Journal of
      Gastrointestinal and Liver Diseases.

PMID- 17205157
TI  - Successful treatment for the rupture of a hepatic metastasis of GIST.

PMID- 17205158
TI  - Oesophago-bronchial fistula secondary to cancer of the oesophagus.

PMID- 17205160
TI  - New routes to organofluorine compounds based on ketenes and the radical transfer
      of xanthates.
AB  - New routes to organofluorine derivatives based mostly on the powerful xanthate
      radical transfer technology are described. A special emphasis is placed on the
      synthesis of trifluoromethyl-substituted structures, including trifluromethyl
      ketones and fluorinated aromatic and heteroaromatic substances of interest to the
      pharmaceutical and agrochemical industries.

PMID- 17205161
TI  - A systems perspective to digital structures in molecular analysis.
AB  - Within the last decade, the advance of miniaturization has opened the window to
      new systems that permit digital and molecular science to intersect, suggesting a
      new role for organic chemistry. Currently, fusion of molecules and electronic
      digits, as well as molecular-based digital structures, have expanded the
      conventional interpretation of the digit. This emergence has already generated
      new technological platforms with unique applications for molecular analysis and
      computation. We provide a brief overview of the conventional understanding of
      digital devices, examine the concept of molecular-based digits, and suggest new
      architectures by examining studies conducted on the compact discs. This analysis
      presents a perspective for the unique interaction of molecules and digits and the
      development of digital-based platforms for molecular analysis.

PMID- 17205162
TI  - Diagnosing viruses by the rolling circle amplified synthesis of DNAzymes.
AB  - Circular DNA is used as a template for the amplified detection of M13 phage ssDNA
      by a rolling circle amplification (RCA) process that synthesizes DNAzyme chains,
      thus enabling the colorimetric or chemiluminescent detection of the analyte.

PMID- 17205163
TI  - A ratiometric fluorescent sensor for phosphates: Zn2+-enhanced ICT and ligand
      competition.
AB  - A pyrene-terpyridine-Zn conjugate has been synthesized and characterized, where
      Zn2+ acts as an electron acceptor to enhance molecular ICT with a large emission
      red-shift (>100 nm). It showed a ratiometric fluorescence change upon addition of
      phosphate anions in buffered aqueous solution. The selective response to
      phosphates or pyrophosphates involved ICT and ligand competition processes.

PMID- 17205164
TI  - Acyl palladium species in synthesis: single-step synthesis of alpha,beta
      unsaturated ketones from acid chlorides.
AB  - Conditions are reported for the facile, one-pot synthesis of alpha,beta
      unsaturated ketones via the palladium-catalysed cross-coupling of acyl chlorides
      with hydrozirconated acetylenes, and its use in the 2-step synthesis of D-5-O
      benzyl deoxyxylulose.

PMID- 17205165
TI  - Bipyridyl ligands as photoactivatable mono- and bis-alkylating agents capable of
      DNA cross-linking.
AB  - The photoactivation of 6,6'-bis-CH2X-[2,2']bipyridinyl-5,5'-diol ligands as mono
      and bis-alkylating agents has been investigated, detecting transient heterocyclic
      quinone methides.

PMID- 17205166
TI  - Photo-Fries reaction in water made selective with a capsule.
AB  - The water soluble capsule formed by a deep cavity cavitand with eight carboxylic
      acid groups controls product distribution during photo-Fries rearrangement of
      naphthyl esters in water by restricting the mobility of primary singlet radical
      pair.

PMID- 17205167
TI  - Homopolymeric pyrrolidine-amide oligonucleotide mimics: Fmoc-synthesis and
      DNA/RNA binding properties.
AB  - By chemically modifying or replacing the backbone of oligonucleotides it is
      possible to modulate the DNA and RNA recognition properties and fine-tune the
      physiochemical properties of oligomers. This is important because it challenges
      our understanding of natural nucleic acid structural and recognition properties
      and can lead to nucleic acid mimics with a wide range of applications in nucleic
      acid targeting, analysis or diagnostics. In this paper we describe the solid
      phase synthesis of pyrrolidine-amide oligonucleotide mimics (POMs) using Fmoc
      peptide chemistry. This required the synthesis of adeninyl, cytosinyl, thyminyl
      and guaninyl pyrrolidine monomers, with Fmoc- and standard acyl-protecting groups
      on the exocyclic amino groups and nucleobases respectively. These monomers were
      used to synthesise several thyminyl and adeninyl POM pentamers, with modest
      coupling efficiency. The pentamers were purified by RP-HPLC, characterised by
      mass spectrometry and their DNA and RNA binding properties were investigated
      using UV thermal denaturation/renaturation experiments. This revealed that all
      the pentamers exhibit strong affinity for complementary nucleic acids. The
      further evaluation of longer mixed-sequence POMs is described in a second
      accompanying paper (R. J. Worthington et al., Org. Biomol. Chem., 2006, DOI:
      10.1039/b613386j).

PMID- 17205168
TI  - Mixed-sequence pyrrolidine-amide oligonucleotide mimics: Boc(Z) synthesis and
      DNA/RNA binding properties.
AB  - Pyrrolidine-amide oligonucleotide mimics (POMs) exhibit promising properties for
      potential applications, including in vivo DNA and RNA targeting, diagnostics and
      bioanalysis. Before POMs can be evaluated in these applications it is first
      necessary to synthesise and establish the properties of fully modified oligomers,
      with biologically relevant mixed sequences. Accordingly, Boc-Z-protected
      thyminyl, adeninyl and cytosinyl POM monomers were prepared and used in the first
      successful solid phase synthesis of a mixed sequence POM, Lys-TCACAACTT-NH2. UV
      thermal denaturation studies revealed that the POM oligomer is capable of
      hybridising with sequence selectivity to both complementary parallel and
      antiparallel RNA and DNA strands. Whilst the duplex melting temperatures (Tm)
      were higher than the corresponding duplexes formed with isosequential PNA, DNA
      and RNA oligomers the rates of association/dissociation of the mixed sequence POM
      with DNA/RNA targets were noticeably slower.

PMID- 17205169
TI  - The use of fullerene substituted phenylalanine amino acid as a passport for
      peptides through cell membranes.
AB  - We report the formation of a fullerene-peptide conjugate via the incorporation of
      a fullerene substituted phenylalanine derivative, "Bucky amino acid" (Baa), to a
      cationic peptide, which acts as a passport for intracellular delivery, enabling
      transport of a range of sequences into HEK-293, HepG2, and neuroblastoma cells
      where the peptides in the absence of the fullerene amino acid cannot enter the
      cell. Delivery of the fullerene species to either the cytoplasm or nucleus of the
      cell is demonstrated. Fullerene peptides based on the nuclear localization
      sequence (NLS), H-Baa-Lys(FITC)-Lys-Lys-Arg-Lys-Val-OH, can actively cross over
      the cell membrane and accumulate significantly around the nucleus of HEK-293 and
      neuroblastoma cells, while H-Baa-Lys(FITC)-Lys8-OH accumulates in the cytoplasm.
      Cellular studies show that the uptake for the anionic peptide Baa
      Lys(FITC)Glu4Gly3Ser-OH is greatly reduced in comparison with the cationic
      fullerene peptides of the same concentration. The hydrophobic nature of the
      fullerene assisting peptide transport is suggested by the effect of gamma
      cyclodextrin (CD) in lowering the efficacy of transport. These data suggest that
      the incorporation of a fullerene-based amino acid provides a route for the
      intracellular delivery of peptides and as a consequence the creation of a new
      class of cell penetrating peptides.

PMID- 17205170
TI  - Enantioselective synthesis of beta2-amino acids using rhodium-catalyzed
      hydrogenation.
AB  - A series of protected beta2-dehydroamino acids has been prepared in three steps
      from commercially available starting materials in good yields. These were used as
      substrates in rhodium-catalyzed asymmetric hydrogenation applying a mixed ligand
      system of monodentate phosphoramidites and phosphines. Optimization of the
      catalyst structure was achieved by high throughput experimentation. High
      enantioselectivities were obtained (up to 91%) with full conversion for a number
      of beta-amino acids.

PMID- 17205171
TI  - Recognition of solvent exposed protein surfaces using anthracene derived
      receptors.
AB  - A new class of receptor is described that can selectively bind to the solvent
      exposed surface of proteins such as cytochrome c and lysozyme with low micromolar
      affinity over cytochrome c551, alpha-lactalbumin, myoglobin and RNase A, under
      physiologically relevant conditions (5 mM phosphate, pH 7.4). The use of
      anthracene as a hydrophobic scaffold allows the receptor to act as a selective
      chemosensor via fluorescence quenching or FRET. The study reveals that co
      operative electrostatic interactions over a large surface area dominate binding.
      Further investigations reveal that the receptor binds to the solvent exposed heme
      edge of cytochrome c inhibiting its reaction with small reducing agents and
      validating the strategy for the disruption of protein function.

PMID- 17205172
TI  - Stereochemical investigation on the construction of poly-functionalized
      bicyclo[3.3.1]nonenones by successive Michael reactions of 2-cyclohexenones.
AB  - A method for the practical construction of poly-functionalized
      bicyclo[3.3.1]nonenones by successive Michael reactions of cyclohexenones with
      acrylates using K2CO3 and TBAB (n-Bu4N+ Br-) was developed. The construction
      could be carried out in both stepwise and one-pot reactions with similar
      tendencies in regioselectivity. The alpha-regioselectivity in the intramolecular
      Michael reaction agreed with that stereoelectronically expected in intermolecular
      reactions based upon consideration of the HOMO orbital profile of the enolate I,
      the precursor to ring-closure, although the reaction site was trisubstituted and
      prone to steric hindrance in most of the examples presented. For the
      acetoxymethylacrylates substituted at either the alpha or gamma position, steric
      hindrance of the substituents (R2 and R3) served as a controlling factor to
      induce high regiocontrol. Facial selection in the protonation of enolate II,
      formed upon ring-closure, was also affected by these substituents. In both the
      intramolecular Michael reaction and the protonation of enolate II, the ammonium
      counter cation played an important role.

PMID- 17205173
TI  - A concise and convergent (formal) total synthesis of huperzine A.
AB  - The first convergent synthesis of the tricyclic skeleton of huperzine A is
      described and includes, as the key step, an efficient regioselective
      intramolecular Heck reaction of 2-(tert-butyldimethylsilyloxymethyl)-6-(2-methoxy
      5-bromopyridin-6-yl)methylcyclohex-2-enol.

PMID- 17205174
TI  - Mitochondrial targeting of radioprotectants using peptidyl conjugates.
AB  - Ionizing radiation activates a mitochondrial nitric oxide synthase, leading to
      inhibition of the respiratory chain, generation of excess superoxide,
      peroxynitrite production and nitrosative damage. We have measured the
      radioprotective effects of a nitric oxide synthase antagonist (AMT) versus a free
      radical scavenger (4-amino-TEMPO) using electrochemical detection of nitric oxide
      and peroxynitrite. To enhance their efficacy, we have conjugated these compounds
      to peptides and peptide isosteres--derived from the antibiotic gramicidin S--that
      target the mitochondria. The targeting ability of these peptidyl conjugates was
      measured using quantitative mass spectrometry.

PMID- 17205175
TI  - Highly selective 4-amino-1,8-naphthalimide based fluorescent photoinduced
      electron transfer (PET) chemosensors for Zn(II) under physiological pH
      conditions.
AB  - The design and synthesis of two novel fluorescent sensors based on the
      photoinduced electron transfer (PET) concept, and , for the detection of zinc
      under competitive media is described. These sensors are based on the 4-amino-1,8
      naphthalimide fluorophore, which has an absorption band centred at 450 nm and
      emits in the green with lambda(max) approximately 550 nm. By functionalizing the
      chromophore with a simple benzyl or ethyl-aryl based iminodiacetate receptor at
      the 4-position, both high selectivity and sensitivity were achieved for the
      sensing of Zn(II) over other competitive transition and Group I and II metal
      ions. These sensors were also shown to be pH independent, with a pKa of 2.3 being
      determined for , which allows these to be used in highly competitive pH media.
      Upon sensing of Zn(II) the fluorescence emission spectrum is 'switched on'
      demonstrating the suppression of PET from the receptor to the fluorophore. For ,
      the sensing of Zn(II) was achieved with Kd = 4 nM when measured in pH 7.4
      buffered solution, in the presence of 1.1 mM of EGTA.

PMID- 17205176
TI  - Synthesis of enantiopure chloroalcohols by enzymatic kinetic resolution.
AB  - 3-Alkenyl and heteroaryl chloroalcohols have been obtained in excellent
      enantiomeric excess (>99%) by enzymatic kinetic resolution using the haloalcohol
      dehalogenase HheC. Yields were close to the theoretical maximum for all
      substrates employed. Furthermore, the applicability of this methodology on
      multigram scale has been established.

PMID- 17205177
TI  - Effect of para-substituents on alkaline earth metal ion extraction by proton di
      ionizable calix[4]arene-crown-6 ligands in cone, partial-cone and 1,3-alternate
      conformations.
AB  - Two carboxylic acid or N-(X)sulfonyl carboxamide groups were incorporated into
      calix[4]arene-crown-6 compounds to afford di-ionizable ligands for use in
      divalent metal ion separations. Acidities of the N-(X)sulfonyl carboxamide groups
      were tuned by variation of the electron-withdrawing properties of X. Cone,
      partial-cone and 1,3-alternate conformations were obtained by different synthetic
      strategies and their structures verified by NMR spectroscopy. Competitive solvent
      extractions of alkaline earth metal cations from aqueous solutions into
      chloroform were performed and the results compared with those reported previously
      for di-ionizable p-tert-butylcalix[4]arene-crown-6 analogues to probe the
      influence of the para-substituent on the calix[4]arene scaffold on extraction
      selectivity and efficiency.

PMID- 17205178
TI  - 2-(4-Tolylsulfonyl)ethoxymethyl (TEM)-a new 2'-OH protecting group for solid
      supported RNA synthesis.
AB  - The 2-(4-tolylsulfonyl)ethoxymethyl (TEM) as a new 2'-OH protecting group is
      reported for solid-supported RNA synthesis using phosphoramidite chemistry. The
      usefulness of the 2'-O-TEM group is exemplified by the synthesis of 12 different
      oligo-RNAs of various sizes (14-38 nucleotides long). The stepwise coupling yield
      varied from 97-99% with an optimized coupling time of 120 s. The synthesis of all
      four pure phosphoramidite building blocks is also described. Two new reliable
      parameters, delta(C2')-delta(C3') and delta(H2')-delta(H3'), have been suggested
      for the characterization of isomeric 2'-O-TEM and 3'-O-TEM as well as other
      isomeric mono 2'/3'-protected ribonucleoside derivatives. The most striking
      feature of this strategy is that the crude RNA prepared using our 2'-O-TEM
      strategy is sufficiently pure (>90%) for molecular biology research without any
      additional purification step, thereby making oligo-RNAs easily available at a
      relatively low cost, saving both time and lab resources.

PMID- 17205179
TI  - Expedient total synthesis of pyrrothine natural products and analogs.
AB  - This paper describes an expedient and straightforward total synthesis of the two
      pyrrothine natural products holomycin (7 steps, 11% overall) and xenorhabdin I (7
      steps, 11% overall) and analogs thereof via a common late-stage intermediate. The
      pathway proceeds via the pyrrothine hydrochloride intermediate (6 steps, 17%
      overall) which also gave access to very fast synthesis of analogs as demonstrated
      by the synthesis of , and (7 steps, 11-12% overall).

PMID- 17205180
TI  - Stereoselective syntheses of piperidinones and their modification by
      organometallic coupling reactions.
AB  - Dehydropiperidinones stereoselectively obtained from N-arabinosyl imines were
      iodinated at the enaminone structure. Knochel iodine-magnesium exchange afforded
      Grignard compounds of these piperidinone derivatives which reacted, either
      directly or after transmetalation to zinc or copper intermediates, with alkyl-,
      aryl- or acylhalides to give correspondingly substituted piperidinones.
      Stereoselective conjugate allyl cuprate addition to a thus obtained 5-allyl
      dehydropiperidinone and ring-closing metathesis of the product gave a
      hydroquinolinone containing three stereogenic centers.

PMID- 17205181
TI  - An efficient and chemoselective synthesis of N-substituted 2-aminopyridines via a
      microwave-assisted multicomponent reaction.
AB  - A facile and selective synthesis of N-substituted 2-aminopyridines is
      accomplished via microwave-assisted multi-component reactions controlled by the
      basicity of amine and the nature of solvent. In addition, a possible mechanism
      accounting for the reaction was proposed.

PMID- 17205182
TI  - Utilization of achiral alkenyl amines for the preparation of high affinity Grb2
      SH2 domain-binding macrocycles by ring-closing metathesis.
AB  - A family of previously reported ring-closing metathesis (RCM)-derived macrocycles
      that exhibit potent Grb2 SH2 domain-binding affinity is characterized by
      stereoselectively-introduced upper ring junctions that bear bicyclic aryl
      substituents. However, the synthetic complexity of these macrocycles presents a
      potential limit to their therapeutic application. Therefore, the current study
      was undertaken to simplify these macrocycles through the use of achiral 4
      pentenylamides as ring-forming components. A series of macrocycles (5a-f) was
      prepared bearing both open and cyclic constructs at the upper ring junction. The
      Grb2 SH2 domain-binding affinities of these macrocycles varied, with higher
      affinities being obtained with cyclo-substituents. The most potent analogue (5d)
      contained a cyclohexyl group and exhibited Grb2 SH2 domain-binding affinity (K(D)
      = 1.3 nM) that was nearly equal to the parent macrocycle (2), which bore a
      stereoselectively-introduced naphthylmethyl substituent at the upper ring
      junction (K(D) = 0.9 nM). The results of this study advance design considerations
      that should facilitate the development of Grb2 SH2 domain-binding antagonists.

PMID- 17205183
TI  - Limb regeneration in amphibians: immunological considerations.
AB  - We review key aspects of what is known about limb regeneration in urodele and
      anuran amphibians, with a focus on the early events of the process that lead to
      formation of the regeneration blastema. This includes the role of the nerves and
      wound epithelium, but also covers the inflammatory effects of the amputation
      trauma and their importance for regenerative growth. We propose that
      immunotolerance is important for limb regeneration and changes in its regulation
      may underlie the loss of regenerative capacity during anuran metamorphosis.

PMID- 17205184
TI  - Limb regeneration in axolotl: is it superhealing?
AB  - The ability of axolotls to regenerate their limbs is almost legendary. In fact,
      urodeles such as the axolotl are the only vertebrates that can regenerate
      multiple structures like their limbs, jaws, tail, spinal cord, and skin (the list
      goes on) throughout their lives. It is therefore surprising to realize, although
      we have known of their regenerative potential for over 200 years, how little we
      understand the mechanisms behind this achievement of adult tissue morphogenesis.
      Many observations can be drawn between regeneration and other disciplines such as
      development and wound healing. In this review, we present new developments in
      functional analysis that will help to address the role of specific genes during
      the process of regeneration. We also present an analysis of the resemblance
      between wound healing and regeneration, and discuss whether axolotls are
      superhealers. A better understanding of these animals' regenerative capacity
      could lead to major benefits by providing regenerative medicine with directions
      on how to develop therapeutic approaches leading to regeneration in humans.

PMID- 17205185
TI  - Limb regeneration in Xenopus laevis froglet.
AB  - Limb regeneration in amphibians is a representative process of epimorphosis. This
      type of organ regeneration, in which a mass of undifferentiated cells referred to
      as the "blastema" proliferate to restore the lost part of the amputated organ, is
      distinct from morphallaxis as observed, for instance, in Hydra, in which
      rearrangement of pre-existing cells and tissues mainly contribute to
      regeneration. In contrast to complete limb regeneration in urodele amphibians,
      limb regeneration in Xenopus, an anuran amphibian, is restricted. In this review
      of some aspects regarding adult limb regeneration in Xenopus laevis, we suggest
      that limb regeneration in adult Xenopus, which is pattern/tissue deficient, also
      represents epimorphosis.

PMID- 17205186
TI  - Transcriptional profiling of caudal fin regeneration in zebrafish.
AB  - Regeneration of severed limbs in adult animals is restricted to urodele
      amphibians. Mammals, including humans, have very limited regenerative
      capabilities and even with proper treatment, only the tips of our digits can grow
      back. Teleost fish can regenerate amputated fins, the evolutionary ancestors of
      limbs. To elucidate the principles of limb-fin regeneration, we performed an
      Affymetrix microarray screen on regenerating caudal fins 12, 24, 48, and 72 h
      post amputation. Approximately 15,000 zebrafish transcripts were analyzed,
      identifying 829 transcripts as differentially expressed during regeneration. Of
      those, 563 were up-regulated and 266 were down-regulated. We constructed a
      comprehensive database containing expression data, functional assignment, and
      background information from the literature for each differentially expressed
      transcript. In order to validate our findings, we employed three approaches: (1)
      microarray expression analysis of genes previously implicated in fin
      regeneration, (2) RT-PCR analysis of genes newly identified as differentially
      expressed during regeneration, and (3) in situ hybridization of the up-regulated
      genes bambi, dlx5A, and her6. Moreover, we show that Smad 1/5/8 proteins,
      effector molecules of Bmp signaling, are phosphorylated during fin regeneration.
      Taken together, we provide a comprehensive database of fin regeneration that will
      serve as an important tool for understanding the molecular mechanisms of
      regeneration.

PMID- 17205187
TI  - Newt opportunities for understanding the dedifferentiation process.
AB  - Urodele amphibians, such as the newt Notophthalmus viridescens, have the unique
      ability to regenerate limbs, spinal cord, eye structures, and many vital organs
      through a process called epimorphic regeneration. Although the cellular basis of
      regeneration has been studied in detail, we know relatively little about the
      molecular controls of the process. This review provides an overview of forelimb
      regeneration in the newt, addressing what we know about cellular and molecular
      aspects. Particular focus is placed on the dedifferentiation process, which
      yields a population of embryonic-like pluripotent cells that will eventually
      reform the lost structure. This cellular plasticity seems to be the key to
      regenerative ability. We discuss the dedifferentiation process in newt forelimb
      regeneration and outline the various studies that have revealed that mammalian
      cells also have the ability to dedifferentiate if given the appropriate triggers.

PMID- 17205188
TI  - Two different transgenes to study gene silencing and re-expression during
      zebrafish caudal fin and retinal regeneration.
AB  - We used the 500-bp Xenopus ef1-alpha promoter and the 2-kb zebrafish histone
      2A.F/Z promoter to generate several independent transgenic zebrafish lines
      expressing EGFP. While both promoters drive ubiquitous EGFP expression in early
      zebrafish development, they are systematically silenced in several adult tissues,
      including the retina and caudal fin. However, EGFP expression is temporarily
      renewed in the adult during either caudal fin or retinal regeneration. In the
      Tg(H2A.F/Z:EGFP)nt line, EGFP is moderately expressed in both the wound
      epithelium and blastema of the regenerating caudal fin. In the Tg(ef1
      alpha:EGFP)nt line, EGFP expression is reinitiated and restricted to the blastema
      of the regenerating caudal fin and colabels with BrdU, PCNA, and msxc-positive
      cells. Thus, these two ubiquitous promoters drive EGFP transgene expression in
      different cell populations during caudal fin regeneration. We further analyzed
      the ability of the ef1-alpha:EGFP transgene to label nonterminally differentiated
      cells during adult tissue regeneration. First, we demonstrated that the transgene
      is highly methylated in adult zebrafish caudal fin tissue, but not during fin
      regeneration, implicating methylation as a potential means of transgene silencing
      in this line. Next, we determined that the ef1-alpha:EGFP transgene is also re
      expressed during adult retinal regeneration. Specifically, the ef1-alpha:EGFP
      transgene colabels with PCNA in the Muller glia, a specialized cell that is the
      source of neuronal progenitors during zebrafish retinal regeneration. Thus, we
      concluded that Tg(ef1-alpha:EGFP)nt line visually marks nonterminally
      differentiated cells in multiple adult regeneration environments and may prove to
      be a useful marker in tissue regeneration studies in zebrafish.

PMID- 17205189
TI  - Characteristics of the endoderm: embryonic and extraembryonic in mouse.
AB  - In mouse, four endodermal lineages are generated during the period from the late
      blastocyst to the end of gastrulation. The characteristics of each lineage and
      the proposed genetic cascades involved in their formation are reviewed. In
      addition, a list of the current markers used to identify these lineages in vivo
      and in vitro is presented.

PMID- 17205190
TI  - MicroRNAs in development.
AB  - Over 10 years ago, the lab of Victor Ambros cloned an unusual gene, lin-4, which
      encodes two small RNA transcripts[1]. In the past few years, hundreds more of
      these tiny transcripts, termed microRNAs (miRNAs), have been uncovered in over a
      dozen species. The functions of the first two miRNAs, lin-4 and let-7, were
      relatively easy to identify since they were found in forward genetic screens in
      Caenorhabditis elegans[1,2,3]. However, uncovering the functions of the growing
      list of miRNAs presents a challenge to developmental biologists. This review will
      describe our current understanding of how miRNAs regulate gene expression and
      will focus on the roles these noncoding RNAs play during the development of both
      invertebrate and vertebrate species.

PMID- 17205191
TI  - The evolution of sensory placodes.
AB  - The vertebrate cranial sensory placodes are ectodermal embryonic patches that
      give rise to sensory receptor cells of the peripheral paired sense organs and to
      neurons in the cranial sensory ganglia. Their differentiation and the genetic
      pathways that underlay their development are now well understood. Their
      evolutionary history, however, has remained obscure. Recent molecular work,
      performed on close relatives of the vertebrates, demonstrated that some sensory
      placodes (namely the adenohypophysis, the olfactory, and accoustico-lateralis
      placodes) first evolved at the base of the chordate lineage, while others might
      be specific to vertebrates. Combined with morphological and cellular fate data,
      these results also suggest that the sensory placodes of the ancestor of all
      chordates differentiated into a wide range of structures, most likely to fit the
      lifestyle and environment of each species.

PMID- 17205192
TI  - Chromatin modification and remodeling in heart development.
AB  - In organogenesis, cell types are specified from determined precursors as
      morphogenetic patterning takes place. These events are largely controlled by
      tissue-specific transcription factors. These transcription factors must function
      within the context of chromatin to activate or repress target genes. Recent
      evidence suggests that chromatin-remodeling and -modifying factors may have
      tissue-specific function. Here we review the potential roles for chromatin
      remodeling and -modifying proteins in the development of the mammalian heart.

PMID- 17205193
TI  - Formation of the ventricles.
AB  - The formation of the ventricles of the heart involves numerous carefully
      regulated temporal events, including the initial specification and deployment of
      ventricular progenitors, subsequent growth and maturation of the ventricles
      through "ballooning" of chamber myocardium, the emergence of trabeculations, the
      generation of the compact myocardium, and the formation of the interventricular
      septum. Several genes have been identified through studies on mouse knockout and
      transgenic models, which have contributed to our understanding of the molecular
      events governing these developmental processes. Interpretation of these studies
      highlights the fact that even the smallest perturbation at any stage of
      ventricular development may lead to cardiac malformations that result in either
      early embryonic mortality or a manifestation of congenital heart disease.

PMID- 17205194
TI  - The 22q11.2 deletion syndrome: a gene dosage perspective.
AB  - The 22q11.2 deletion/DiGeorge syndrome is a relatively common "genomic" disorder
      that results from heterozygous deletion of a 3-Mbp segment of chromosome 22. Of
      the more than 30 genes deleted in this syndrome, TBX1 is the only one that has
      been found to be mutated in some patients with a phenotype that is very similar
      to that of patients with the full deletion, suggesting that TBX1
      haploinsufficiency is a major contributor to the syndrome's phenotype. Multi- and
      single-gene mouse models have provided a considerable amount of information about
      the consequences of decreased and increased dosage of the genomic region (and in
      particular of the Tbx1 gene) on mouse embryonic development. Modified alleles of
      Tbx1, as well as conditional ablation strategies have been utilized to map in
      vivo the tissues and developmental stages most sensitive to gene dosage. These
      experiments have revealed substantially different sensitivity to gene dosage in
      different tissues and at different times, underlying the importance of the
      developmental context within which gene dosage reduction occurs.

PMID- 17205195
TI  - Genomic imprinting and cancer: from primordial germ cells to somatic cells.
AB  - Imprinted genes are a subset of genes that are expressed from only one of the
      parental alleles. The majority of imprinted genes have roles in growth regulation
      and are, therefore, potential oncogenes or tumour suppressors. Cancer is a
      disease of aberrant cell growth and is characterised by genetic mutations and
      epigenetic changes such as DNA methylation. The mechanisms whereby imprinting is
      maintained in somatic cells and then erased and reset in the germline parallels
      epigenetic changes that cancer cells undergo. This review summarises what we know
      about imprinting in stem cells and how loss of imprinting may contribute to
      neoplasia.

PMID- 17205196
TI  - DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A): a
      gene with dosage effect during development and neurogenesis.
AB  - DYRKs (dual-specificity tyrosine-regulated kinases) are an emerging family of
      evolutionarily conserved dual-specificity kinases that play key roles in cell
      proliferation, survival, and development. The research in the last years suggests
      a relevant conserved function during neuronal development, related to
      proliferation and/or differentiation for DYRK1A. It is expressed in neural
      progenitor cells and has been proposed to participate in the signaling mechanisms
      that regulate dendrite differentiation. In Drosophila, disruption of the homolog
      minibrain gene results in flies with reduced neuroblast proliferation, decreased
      numbers of central brain neurons, and learning/memory deficits. Knockout DYRK1A
      mice are embryonic lethal, and heterozygotes show decreased viability and region
      specific reductions in brain size. In humans, DYRK1A has been proposed to be
      involved in the neurodevelopmental alterations associated with Down syndrome. The
      large number of protein interaction and putative substrates described for DYRK1A
      suggest multiple pathways and functions to be involved in its developmental
      function. This review focuses on the functional role that DYRK1A plays in brain
      development.

PMID- 17205197
TI  - Function and diversification of MADS-box genes in rice.
AB  - MADS-box genes play critical roles in a number of developmental processes in
      flowering plants, such as specification of floral organ identity, control of
      flowering time, and regulation of fruit development. Because of their crucial
      functions in flower development, diversification of the MADS-box gene family has
      been suggested to be a major factor responsible for floral diversity during
      radiation of the flowering plants. Inflorescences and flowers in the grass
      species have unique structures that are distinct from those in eudicots. Thus, it
      is plausible that the diversification of the function of MADS-box genes may have
      been a key driving force in the morphological divergence of the flowers and
      inflorescences in the grasses. Indeed, recent progress in genetic studies has
      shown that MADS-box genes function in flower development in Oryza sativa (rice),
      in support of the idea that functional diversification of the MADS-box genes was
      involved in evolution of the angiosperms. In this review, we summarize the
      functions of the major subfamilies of the MADS-box genes in rice and discuss
      their role in the development and evolution of rice flowers and inflorescences.

PMID- 17205198
TI  - The orchid MADS-box genes controlling floral morphogenesis.
AB  - Orchids are known for both their floral diversity and ecological strategies. The
      versatility and specialization in orchid floral morphology, structure, and
      physiological properties have fascinated botanists for centuries. In floral
      studies, MADS-box genes contributing to the now famous ABCDE model of floral
      organ identity control have dominated conceptual thinking. The sophisticated
      orchid floral organization offers an opportunity to discover new variant genes
      and different levels of complexity to the ABCDE model. Recently, several
      remarkable research studies done on orchid MADS-box genes have revealed the
      important roles on orchid floral development. Knowledge about MADS-box genes'
      encoding ABCDE functions in orchids will give insights into the highly evolved
      floral morphogenetic networks of orchids.

PMID- 17205199
TI  - Developmental defects in trisomy 21 and mouse models.
AB  - Aneuploidies have diverse phenotypic consequences, ranging from mental
      retardation and developmental abnormalities to susceptibility to common
      phenotypes and various neoplasms. This review focuses on the developmental
      defects of murine models of a prototype human aneuploidy: trisomy 21 (Down
      syndrome, DS, T21). Murine models are clearly the best tool for dissecting the
      phenotypic consequences of imbalances that affect single genes or chromosome
      segments. Embryos can be studied freely in mice, making murine models
      particularly useful for the characterization of developmental abnormalities. This
      review describes the main phenotypic alterations occurring during the development
      of patients with T21 and the developmental abnormalities observed in mouse
      models, and investigates phenotypes common to both species.

PMID- 17205200
TI  - Mesenteric fibromatosis as a potential source of false-positive interpretation of
      FDG-PET: report of a case.

PMID- 17205201
TI  - Long-axis rotational volvulus in a W ileoanal pouch: an unusual but potentially
      preventable problem. Report of a case.
AB  - PURPOSE: This study was designed to report long-axis rotational volvulus, an
      unusual long-term complication of restorative proctocolectomy. METHODS: A MEDLINE
      search using the keywords, pouch volvulus, pouch complications, ileoanal pouch
      volvulus, restorative proctocolectomy volvulus, restorative proctocolectomy
      complications, W-pouch, and early and late complications, was performed and
      yielded no previous reports. RESULTS: We describe pouch gangrene secondary to
      volvulus in a W-pouch four years after restorative proctocolectomy for ulcerative
      colitis. Early recognition by clinical features, pouchoscopy, and soluble
      contrast studies are crucial if pouch salvage by pouchpexy is to be successful.
      CONCLUSIONS: Acute necrosis of the ileoanal pouch caused by long-axis rotational
      volvulus is an important, but uncommon, cause of life-threatening acute abdomen
      after restorative proctocolectomy. Prophylactic pouchpexy at the time of pouch
      construction or salvage pouchpexy after early diagnosis of the at-risk pouch are
      important considerations to avoid loss of the pouch.

PMID- 17205202
TI  - Transient profound mesenteric ischemia strongly affects the strength of
      intestinal anastomoses in the rat.
AB  - PURPOSE: Experimental data suggest that transient preoperative ischemia and
      reperfusion may compromise anastomotic strength. However, data on this subject
      are equivocal, in particular as to the onset and duration of this effect. This
      study was designed to comprehensively characterize the effects of profound
      transient intestinal ischemia on anastomotic healing during the first
      postoperative week. METHODS: Ischemia was induced in rats by clamping both the
      superior mesenteric artery and ileal branches for 30 minutes. Immediately after
      declamping, anastomoses were constructed in both terminal ileum and descending
      colon. After three, five, or seven days, both bursting pressure and breaking
      strength were measured. Anastomotic collagen content, gelatinase activity, and
      histology were analyzed. RESULTS: Anastomotic leakage rate was 13 percent in
      ischemia-reperfusion group and 0 percent (P=0.02) in controls. The breaking
      strength in ileum remained significantly (P<0.05) lower in the ischemic groups
      than in the control groups at all time points. Bursting pressure in the ileum was
      not significantly different between ischemic and control groups at either of the
      time points measured. However, at Day 7 the bursting site was significantly more
      frequent within the suture line in the ischemic groups. In the colon, at Day 3
      the bursting pressure was 35 percent lower in the ischemic group than in the
      control group (P<0.05). Anastomotic collagen content and gelatinase activity were
      similar in ischemic and control groups. CONCLUSIONS: Transient profound
      splanchnic ischemia compromises anastomotic strength throughout the entire first
      postoperative week. This effect does not seem to be caused by impaired
      accumulation of wound collagen.

PMID- 17205203
TI  - An algorithm for the management of sigmoid colon volvulus and the safety of
      primary resection: experience with 827 cases.
AB  - PURPOSE: This study was designed to review the outcomes of emergent treatment of
      sigmoid colon volvulus. METHODS: The records of 827 patients were reviewed
      retrospectively. RESULTS: The mean age was 57.9 years (range, 10 weeks to 98
      years), and 688 patients (83.2 percent) were male. Nonoperative reduction was
      applied in 575 patients (barium enema in 13, rigid sigmoidoscopy in 351, and
      flexible sigmoidoscopy in 211, with rectal tube placement in all patients). The
      results were as follows: success of 78.1 percent, mortality of 0.9 percent,
      complication of 3 percent, and early recurrence of 3.3 percent. Surgical
      treatment was performed on 393 patients (detorsion in 46, mesosigmoidopexy in 56,
      exteriorization in 4, resection with Hartmann's procedure in 146, resection with
      Mikulicz procedure in 14, resection with primary anastomosis in 51, tube
      cecostomy and colonic cleansing with resection in 75, and laparotomy in 1). The
      results were as follows: mortality of 15.8 percent, complication of 37.2 percent,
      early recurrence of 0.8 percent, and late recurrence of 6.7 percent. CONCLUSIONS:
      Nonoperative reduction is the initial treatment of sigmoid colon volvulus, and
      flexible sigmoidoscopy with rectal tube placement can be used successfully.
      Patients in whom bowel gangrene or peritonitis is present or nonoperative
      treatment is unsuccessful need emergency surgery. In surgical treatment,
      resection and primary anastomosis is the first choice, and it can be performed
      with acceptable mortality and morbidity rates if the patient is stable and a
      tension-free anastomosis is possible. Nondefinitive procedures have high
      recurrence rates; thus, definitive surgical techniques must be preferred.

PMID- 17205204
TI  - Pharmacotherapy for fecal incontinence: a review.
AB  - Fecal incontinence is a common clinical problem that often is frustrating to the
      patient and treating physician. Nonsurgical management for fecal incontinence
      includes dietary manipulation, Kegel exercises, perianal skin care, and
      biofeedback therapy. Pharmacotherapies often are used to assist in management of
      fecal incontinence. A variety of pharmacotherapies have been utilized for the
      management of fecal incontinence; limited data from randomized, placebo
      controlled trials are available. This is a review of the existing literature on
      clinical trials of several classes of drugs and other medical therapies that may
      be beneficial for patients with fecal incontinence. The information in this
      article was obtained by a MEDLINE search for all clinical trials of drug therapy
      for fecal incontinence. These treatments and the existing data on their use are
      summarized. Treatments reviewed include stool bulking agents, with an emphasis on
      the most promising effect obtained with calcium polycarbophil, constipating
      agents, including loperamide, codeine, amitriptyline, atropine, and diphenoxylate
      agents injected into the anal sphincter, drugs to enhance anal sphincter
      function, including topical phenylepherine and oral sodium valproate, and trials
      of fecal disimpaction. A new classification to easily remember the treatment
      categories for this condition, based on the "ABCs of treatment for fecal
      incontinence," has been introduced into the structure of this review.

PMID- 17205205
TI  - Female bowel function: the real story.
AB  - PURPOSE: There has been minimal research done on normal female bowel habits.
      Because we do not know what is normal, this affects counseling of patients and
      research. The aim of this study was to conduct a survey of females with no bowel
      pathology to obtain a baseline of normal bowel function and examine any normal
      changes that occur during a woman's lifetime. METHODS: Females accompanying
      patients to our hospital and clinic were invited to fill out an IRB-approved
      questionnaire after excluding those with current bowel pathology, depression, a
      stoma, or were wheelchair bound. RESULTS: Four hundred twenty-five of 528
      questionnaires of females who reported they had normal bowel habits were
      evaluated. The age range was from 18 to 80 years and comparison was according to
      age, race, and parity. Fifty-one percent had one bowel movement daily while 30
      percent reported fewer. Overall, 15 percent reported constipation, which was
      higher in African-American females (26 percent) vs. Caucasian females (14
      percent), P = 0.08. The average time for a bowel movement was 5-6 minutes, which
      was longer in African-American females (7.7 min) vs. Caucasian (5.0 min), P =
      0.002. Younger females had changes in their bowel pattern reported as soft stool
      usually associated with their menstrual cycle; this was seen mostly in single
      females. Menopause did not affect bowels. Thirty-six percent of parous females
      reported occasional stool incontinence. Flatal incontinence was seen occasionally
      in over 50 percent of females, more frequently in those over 35 years old.
      Seventy-four percent of parous females reported incontinence to gas. One-third of
      females read on the toilet, with a majority doing so to relax or to be distracted
      and with African-American females reading more (54 percent) vs. Caucasian (32
      percent), P = 0.004. Interestingly, Caucasian females read to conserve time (26
      percent) vs. African-Americans (4 percent), P = 0.02. Fiber as a supplement was
      taken by only 8 percent. Foods affected bowel function in all age groups, while
      travel and exercise did not. Stress affected a change in 35 percent in the 18 to
      50-year group. CONCLUSION: There is a vast diversity in what is considered normal
      female bowel habits. One daily bowel movement is not the norm. Normal older
      females and those who have had children report more flatal incontinence. One
      third experience some element of fecal incontinence. Foods most commonly caused a
      change in bowel pattern, followed by menstruation, stress, and childbirth. A vast
      majority do not take fiber as a supplement.

PMID- 17205206
TI  - A yeast glycolipid biosurfactant, mannosylerythritol lipid, shows high binding
      affinity towards lectins on a self-assembled monolayer system.
AB  - Mannosylerythritol lipids (MEL), which are glycolipid biosurfactants secreted by
      the Pseudozyma yeasts, show not only excellent surface-active properties but also
      versatile biochemical actions including antitumor and cell-differentiation
      activities. In order to address the biochemical actions, interactions between MEL
      A, the major component of MEL, and different lectins were investigated using the
      surface plasmon resonance spectroscopy. The monolayer of MEL-A showed high
      binding affinity to concanavalin A (ConA) and Maackia amurensis lectin-I (MAL-I).
      The observed affinity constants for ConA and MAL-I were estimated to be 9.48 +/-
      1.31 x 10(6) and 3.13 +/- 0.274 x 10(6) M(-1), respectively; the value was
      comparable to that of Manalpha1-6(Manalpha1-3)Man, which is one of the most
      specific probe to ConA. Significantly, alpha-methyl-D-mannopyranoside (1 mM)
      exhibited no binding inhibition between MEL-A and ConA. MEL-A is thus likely to
      self-assemble to give a high affinity surface, where ConA binds to the
      hydrophilic headgroup in a different manner from that generally observed in
      lectin-saccharide interactions. The binding manner should be related with the
      biochemical actions of MEL toward mammalian cells via protein-carbohydrate
      interactions.

PMID- 17205207
TI  - Functional and genetic analysis of the Saccharomyces cerevisiae RNC1/TRM2:
      evidences for its involvement in DNA double-strand break repair.
AB  - We previously isolated the RNC1/TRM2 gene and provided evidence that it encodes a
      protein with a possible role in DNA double strand break repair. RNC1 was
      independently re-isolated as the TRM2 gene encoding a methyl transferase involved
      in tRNA maturation. Here we show that Trm2p purified as a fusion protein
      displayed 5' --> 3' exonuclease activity on double-strand (ds) DNA, and
      endonuclease activity on single-strand (ss) DNA, properties characteristic of
      previously isolated endo-exonucleases. A variant of Trm2p, Trm2p(ctDelta76aa)
      lacking 76 amino acids at the C-terminus retained nuclease activities but not the
      methyl transferase activity. Both the native and the variant exhibited
      sensitivity to the endo-exonuclease inhibitor pentamidine. The Saccharomyces
      cerevisiae trm2(Delta232-1920nt) mutant (containing only the first 231
      nucleotides of the TRM2 gene) displayed low sensitivity to methyl methane
      sulfonate (MMS) and suppressed the MMS sensitivity of rad52 mutants in
      trm2(Delta232-1920nt)rad52 double mutants. The deletion of KU80, in trm2(Delta232
      1920nt) mutant background displayed higher MMS sensitivity supporting the view of
      the possible role of Trm2p in a competing repair pathway separate from NHEJ. In
      addition, trm2 exo1 double mutants were synergistically more sensitive to MMS and
      ionizing radiation than either of the single mutant suggesting that TRM2 and EXO1
      can functionally complement each other. However, the C-terminal portion, required
      for its methyl transferase activity was found not important for DNA repair. These
      results propose an important role for TRM2 in DNA repair with a potential
      involvement of its nuclease function in homologous recombination based repair of
      DNA DSBs.

PMID- 17205208
TI  - Nickel-binding and accessory proteins facilitating Ni-enzyme maturation in
      Helicobacter pylori.
AB  - Helicobacter pylori colonizes the human gastric mucosa and this can lead to
      chronic gastritis, peptic and duodenal ulcers, and even gastric cancers. The
      bacterium colonizes over one-half of the worlds population. Nickel plays a major
      role in the bacteriums colonization and persistence attributes as two nickel
      enzyme sinks obligately contain the metal. Urease accounts for up to 10% of the
      total cellular protein made and is required for initial colonization processes,
      and the hydrogen oxidizing hydrogenase provides the bacterium a high-energy
      substrate yielding low potential electrons for energy generation. A battery of
      accessory proteins are needed for maturation or activation of each of the
      apoenzymes. These include Ni-chaperones and GTPases, some of which are unique to
      each Ni-enzyme and others that are individually required for maturation of both
      the Ni-enzymes. H. pylori's need for some conventional hydrogenase maturation
      proteins playing roles in urease maturation may have to do with the poor nickel
      sequestering ability of the UreE urease maturation protein compared to other
      systems. H. pylori also possesses a NixA nickel specific permease, a nickel
      dependent regulator (NikR), a recently identified nickel efflux system (CznABC),
      and a histidine-rich heat shock protein, HspA. Based on mutant analysis
      approaches all these proteins have roles in nickel homeostasis, in urease
      expression, and in host colonization. The His-rich putative nickel storage
      proteins Hpn and Hpn-like play roles in nickel detoxification and may influence
      the levels of Ni-activated urease that can be achieved.

PMID- 17205209
TI  - Metabolic regulation of citrate and iron by aconitases: role of iron-sulfur
      cluster biogenesis.
AB  - Iron and citrate are essential for the metabolism of most organisms, and
      regulation of iron and citrate biology at both the cellular and systemic levels
      is critical for normal physiology and survival. Mitochondrial and cytosolic
      aconitases catalyze the interconversion of citrate and isocitrate, and aconitase
      activities are affected by iron levels, oxidative stress and by the status of the
      Fe-S cluster biogenesis apparatus. Assembly and disassembly of Fe-S clusters is a
      key process not only in regulating the enzymatic activity of mitochondrial
      aconitase in the citric acid cycle, but also in controlling the iron sensing and
      RNA binding activities of cytosolic aconitase (also known as iron regulatory
      protein IRP1). This review discusses the central role of aconitases in
      intermediary metabolism and explores how iron homeostasis and Fe-S cluster
      biogenesis regulate the Fe-S cluster switch and modulate intracellular citrate
      flux.

PMID- 17205210
TI  - "Trade-off" in Antarctic bacteria: limnetic psychrotrophs concede multiple enzyme
      expressions for multiple metal resistance.
AB  - The present study examines the metal and antibiotic resistant bacteria in ice and
      water from lakes east and west of the Indian base camp (Maitri) in Antarctica.
      The isolates from western and eastern lakes showed distinct geographical
      differences in properties like metal resistance and enzyme expression. This may
      be attributed to high organic loading in the lakes on the west of Maitri.
      However, there was no marked geopraphical distinction in antibiotic resistance
      between the lakes. Bacteria from the lakes on the eastern side showed resistance
      to three or more metals including mercury while, those from the western were
      resistant to only 1-2 metals excluding mercury. Multiple enzyme expression was
      more pronounced in the lakes on the western side. On the eastern side multiple
      metal resistance was encountered in bacterial isolates associated with fewer
      enzyme expressions suggesting a "trade-off". Thus these Antarctic isolates from
      the east trade their ability to express multiple enzymes for developing
      resistance to multiple metals including mercury.

PMID- 17205211
TI  - Effective triplet interactions in nematic colloids.
AB  - Three-body effective interactions emerging between parallel cylindrical rods
      immersed in a nematic liquid crystals are calculated within the Landau-de Gennes
      free-energy description. Collinear, equilateral and midplane configurations of
      the three colloidal particles are considered. In the last two cases the effective
      triplet interaction is of the same magnitude and range as the pair one.

PMID- 17205212
TI  - Lateral vibration of a water drop and its motion on a vibrating surface.
AB  - The resonant modes of sessile water drops on a hydrophobic substrate subjected to
      a small-amplitude lateral vibration are investigated using computational fluid
      dynamic (CFD) modeling. As the substrate is vibrated laterally, its momentum
      diffuses within the Stokes layer of the drop. Above the Stokes layer, the
      competition between the inertial and Laplace forces causes the formation of
      capillary waves on the surface of the drop. In the first part of this paper, the
      resonant states of water drops are illustrated by investigating the velocity
      profile and the hydrostatic force using a 3d simulation of the Navier-Stokes
      equation. The simulation also allows an estimation of the contact angle variation
      on both sides of the drop. In the second part of the paper, we investigate the
      effect of vibration on a water drop in contact with a vertical plate. Here, as
      the plate vibrates parallel to gravity, the contact line oscillates. Each
      oscillation is, however, rectified by hysteresis, thus inducing a ratcheting
      motion to the water droplet vertically downward. Maximum rectification occurs at
      the resonant states of the drop. A comparison between the frequency-dependent
      motion of these drops and the variation of contact angles on their both sides is
      made. The paper ends with a discussion on the movements of the drops on a
      horizontal hydrophobic surface subjected to an asymmetric vibration.

PMID- 17205213
TI  - Henoch-Schonlein purpura nephritis complicated by reversible posterior
      leukoencephalopathy syndrome.
AB  - We report a young female patient with Henoch-Schonlein purpura (HSP) nephritis
      complicated by reversible posterior leukoencephalopathy syndrome (RPLS). The
      patient suddenly showed generalized seizures and cortical blindness with severe
      hypertension due to renal insufficiency approximately 1 year after cessation of
      corticosteroid treatment for HSP nephritis. Magnetic resonance imaging (MRI)
      demonstrated bilateral abnormal signals mainly in the cerebellum and white matter
      of the occipital lobe. Clinical symptoms quickly improved in conjunction with
      disappearance of abnormal signals on brain MRI after starting control of
      hypertension and continuous hemodiafiltration with steroid pulse therapy and
      plasmapheresis. RPLS may be caused by vasculitis and also by hemodynamic change
      due to severe hypertension in HSP, particularly in patients with nephropathy. In
      such cases intensive treatment should be performed as soon as possible to avoid
      neurological sequelae.

PMID- 17205214
TI  - Serum hyaluronan levels in patients with knee osteoarthritis.
AB  - We examined the association between clinical parameters of disease activity and
      serum hyaluronic acid (HA) level in patients with knee osteoarthritis (OA). Fifty
      eight patients with knee OA and 40 healthy individuals were included in this
      study. Demographic data were noted. The radiological evaluation was done
      according to Kellgren/Lawrence Grading System. Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC) was used in evaluating the clinical
      disability caused by OA. Erythrocyte sedimentation rate (ESR) and serum C
      reactive protein (CRP) level were determined in laboratory evaluations. Serum HA
      levels (in nanogram per milliliter) of both groups were measured by enzyme-linked
      immunosorbent assay. The mean ages of patients in OA group and control group were
      57.58 (9.55) and 43.3(10.2) years, respectively. There was a significant
      difference between HA levels of both groups (p=0.02). Also, there was a
      significant correlation between HA level and disease duration (p=0.04), ESR
      (p=0.001), and CRP level (p<0.001). However, there was no significant correlation
      between HA levels with WOMAC and radiological grade (p>0.05). There is no
      satisfactory amount of data regarding HA level in OA. In our study, we
      demonstrated that HA was in high levels in the serum of patients with OA. We
      suggest that serum HA levels may be used as a marker to determine the disease
      activity.

PMID- 17205215
TI  - Distinct expression of mast cell tryptase and protease activated receptor-2 in
      synovia of rheumatoid arthritis and osteoarthritis.
AB  - The objective of this study is to examine the differential expression of mast
      cell tryptase and its receptor, protease-activated receptor-2 (PAR-2), in the
      synovium and synovial fluid of patients with rheumatoid arthritis (RA) and
      osteoarthritis (OA). Biochemical and immunohistochemical analyses were performed
      to determine whether the trypsin-like protease in the synovium is identical to
      mast cell tryptase. The effects of mast cell tryptase on the proliferation of
      synovial fibroblast-like cells (SFCs) and the release of IL-8 thereof were
      evaluated by the [3H]-thymidine incorporation and ELISA, respectively. The
      trypsin-like protease in the synovium of RA patients was identical to human mast
      cell tryptase, which was composed of two subunits: 33 and 34 kDa. The 33- and 34
      kDa proteins are different glycosylated forms of the 31-kDa protein, which was
      unglycosylated. Mast cell tryptase activity in RA synovial fluid was
      significantly higher than that in OA synovial fluid, while their activities and
      expression in the synovium were similar. Expression of PAR-2 mRNA in the synovium
      was higher in RA than in OA. Mast cell tryptase containing the unglycosylated 31
      kDa subunit was the predominant form in synovial fluid. RA patients had higher
      amounts of this subunit in their synovial fluid than OA patients. Mast cell
      tryptase and PAR-2 activating peptide stimulated the proliferation of SFCs and
      release of IL-8 from these cells. Mast cell tryptase secretion into RA synovial
      fluid is higher than OA synovial fluid. Mast cell tryptase in synovial fluid
      stimulates the proliferation of SFCs and the release of pro-inflammatory
      cytokines via PAR-2, which may contribute to exacerbation of synovitis in RA.

PMID- 17205216
TI  - Systemic polyarteritis nodosa associated with acute Epstein-Barr virus infection.
AB  - Polyarteritis nodosa (PAN) is a rare cause of systemic vasculitis in children,
      affecting medium and small-sized arteries. We report on a patient who presented
      with prolonged fever, shock, acute renal failure with nephrotic range
      proteinuria, hypertension, and sudden deterioration of consciousness. Cranial
      tomography revealed a left extensive hemorrhagic lesion. Renal biopsy revealed a
      large fibrinoid necrosis lesion consistent with PAN. Epstein-Barr virus (EBV)
      infection was confirmed by real-time polymerase chain reaction (RT-PCR) detection
      of EBV DNA. The patient was successfully treated with oral prednisolone and
      intravenous pulse of cyclophosphamide. To our knowledge, this is the first
      reported case of c-PAN related to active EBV infection.

PMID- 17205217
TI  - Brazilian-Portuguese version of the Health Assessment Questionnaire for
      Spondyloarthropathies (HAQ-S) in patients with ankylosing spondylitis: a
      translation, cross-cultural adaptation, and validation.
AB  - To translate and cross-culturally adapt to the Brazilian-Portuguese language
      (BP), five items were added to Health Assessment Questionnaire (HAQ) to validate
      the resulting HAQ-S BP version for ankylosing spondylitis (AS). The items were
      translated into BP following translation and back-translation. To assess
      validity, 25 patients were evaluated using the HAQ, Bath AS Functional Index
      (BASFI), Bath AS Disease Activity Index (BASDAI), Bath AS Metrology Index
      (BASMI), and laboratory variables (erythrocyte sedimentation rate, C-reactive
      protein). One question required modification to adapt culturally to Brazilian
      conditions. The test-retest and interobserver correlation coefficients were 0.990
      (p<0.05) and 0.993 (p<0.05), respectively. HAQ-S BP correlated to BASFI (r=0.574;
      p<0.05) and to HAQ (r=0.963; p<0.05), but not to BASDAI (r=0.282), BASMI
      (r=0.194), and laboratory variable. Individually, the fifth item referring to
      driving correlated highly to neck rotation (r=0.900; p<0.05), while the HAQ-S BP
      correlated to the neck rotation component (r=0.303), but did not reach
      statistical significance. The HAQ-S BP version demonstrated adequate
      reproducibility, internal consistency and validity, confirming its utility in the
      research of AS in Brazil.

PMID- 17205218
TI  - Urethral pressure response patterns induced by squeeze in continent and
      incontinent women.
AB  - Our aim was to compare the urethral pressure response pattern to pelvic floor
      muscle contractions in 20-27 years old, nulliparous continent women (n = 31) to
      that of continent (n = 28) and formerly untreated incontinent (n = 59) (53-63
      years old) women. These women underwent urethral pressure measurements during
      rest and repeated pelvic muscle contractions. The response to the contractions
      was graded 0-4. The young continent women showed a mean urethral pressure
      response of 2.8, the middle-aged continent women 2.2 (NS vs young continent), and
      the incontinent women 1.5 (p < 0.05 vs middle-aged continent, p < 0.001 vs young
      continent). Urethral pressures during rest were significantly higher in the
      younger women than in both groups of middle-aged women. The decreased ability to
      increase urethral pressure on demand seen in middle-aged incontinent women
      compared to continent women of the same age as well as young women seems to be a
      consequence of a neuromuscular disorder rather than of age.

PMID- 17205219
TI  - The effect of ovariectomy on biomarkers of urogenital ageing in old versus young
      adult rats.
AB  - The aim of this study was to compare the effects of ageing and ovariectomy on
      biomarkers of urogenital ageing in old and young-adult rats. Fisher 344 rats (18-
      and 3-months-old, n = 6 x 2) underwent ovariectomy. Age-matched sham animals
      received no intervention (n = 6 x 2). One month later, biomarkers of urogenital
      ageing were evaluated (light microscopic count of urethral and anal canal
      submucosal blood vessels, Western blot analysis of urethral, and anal canal
      submucosal collagen I and III and cytoplasmic p27(kip1) expression in the
      striated urethral and anal sphincters and levator ani and gel electrophoresis of
      isomyosin I proportion in these muscles) and compared in all groups (n = 24). All
      biomarkers of urogenital ageing studied were significantly increased in old
      compared to young-adult sham rats. Ovariectomy significantly increased these
      changes further in old versus young-adult rats with either smaller or larger
      differential effect than ageing compared to young-adult sham animals. Ovariectomy
      significantly exacerbates normative urogenital ageing changes in rats.

PMID- 17205220
TI  - Adequacy of urine cytology specimens: an assessment of collection techniques.
AB  - The objective of this study was to determine whether the method of urine
      collection impacts the adequacy and cell counts of cytology specimens in a low
      risk population. Voided, post-cystometrogram (CMG), and bladder irrigant
      specimens were collected and evaluated for cytologic adequacy and average cell
      count by a single cytopathologist masked to the source of each sample. Data were
      analyzed to detect differences in specimen adequacy and cell counts based on
      method of collection. Both the voided and post-CMG specimens (97.3%, 93.7%
      respectively) were significantly more likely to be adequate compared to the
      bladder irrigant specimen (11.7%, p < 0.0001). The spontaneously voided specimen
      (211.4 +/- 100.1) had significantly higher cell counts than both the post-CMG
      specimen (85.9 +/- 86.6) and the cystoscopy specimen (6.4 +/- 19.6, p < 0.0001).
      In a multivariate linear model, collection method and specimen adequacy were
      associated with increased cell count/hpf (p < 0.001), as was the presence of
      hematuria on urine dipstick (p = 0.03). No cytologic abnormalities were
      diagnosed. Whereas both spontaneously voided and post-CMG specimens were
      consistently adequate for interpretation, spontaneous voided specimens were
      optimal with regard to maximizing cell count/hpf.

PMID- 17205221
TI  - Bone cross-sectional geometry in adolescents and young women with anorexia
      nervosa: a hip structural analysis study.
AB  - INTRODUCTION: Better characterization of bone geometry in adolescents with
      anorexia nervosa (AN) may improve understanding of skeletal deficits in this
      population. Our objective was to determine whether hip cross-sectional geometry
      and bone strength were altered in adolescents with AN. METHODS: Measurements of
      the left total proximal femur and body composition were obtained in 85
      adolescents with AN and 61 healthy controls by dual X-ray absorptiometry. The Hip
      Structural Analysis (HSA) program was used to determine aBMD, cross-sectional
      area (CSA), and section modulus (Z) at the femoral neck and shaft. Strength
      indices were calculated and corrected for lean mass. RESULTS: Femoral neck and
      shaft aBMD were lower in AN patients than healthy controls (-36% and -29%, p <
      0.001). In both regions, bone CSA and Z were lower in AN sufferers (-11 to -35%,
      p < 0.001). While lean body mass correlated with HSA variables (r = 0.48 to 0.58,
      p < 0.001), body fat did not. AN sufferers had lower indices of both whole bone
      strength (-40%, p < 0.001) and relative bone strength (-36%, p < 0.001) than
      controls. CONCLUSIONS: Anorexia nervosa sufferers had decreased resistance to
      axial (CSA) and bending loads (Z) compared with healthy controls. Differences in
      strength properties were significant even when adjusted for lean mass, suggesting
      that not only decreased mechanical loading, but also known metabolic differences
      are likely responsible for deficits in bone strength in these patients.

PMID- 17205222
TI  - Survival among elderly Italian patients with dementia treated with atypical
      antipsychotics: observational study.
AB  - The objective was to compare survival in a population-based cohort of elderly
      demented patients with behavioural and psychological symptoms (BPSD) dispensed an
      atypical antipsychotic (AA) with that of a sample of demented patients not
      treated with AAs. An observational cohort study was carried out in the province
      of Modena, Italy (644,000 inhabitants) on a cohort of 294 patients with BPSD
      diagnosed by a dementia specialist and treated with an AA, and a cohort of 2020
      demented adults not dispensed AAs. All patients were 65 years of age or older.
      Measured outcomes were death by any cause and death by cerebrovascular accident
      at the end of the study. After a median follow-up of one year, survival was not
      significantly different between patients treated and not treated with AAs
      (overall mortality rates: 0.52 vs. 0.55/1000 years/person, respectively; relative
      risk reduction 0.047, 95% confidence interval -0.251 to 0.286). Multivariate
      survival analysis showed that older age at entry, male gender, severe dementia
      and functional impairment were associated with a higher risk of death. Although
      our sample size does not allow the exclusion of small differences in the short
      term, age, gender and dementia severity but not treatment with AAs seem to
      influence survival among elderly demented patients.

PMID- 17205223
TI  - Italian neuropsychological instruments to assess memory, attention and frontal
      functions for developmental age.
AB  - In this study, a series of tests exploring long-term verbal memory (the Short
      Story Test), attention (a modified version of Attentional Matrices and the Trail
      Making Test) and frontal functions (a modified version of the Frontal Assessment
      Battery) have been standardised on an Italian population of 283 children aged 5
      14. Raw scores for each test have been adjusted for a series of variables
      (child's age, years of parents' education, handedness, gender) and transformed in
      equivalent scores enabling direct comparison across measures. This study was
      promoted by LICE (the Italian League Against Epilepsy) in order to provide
      Italian instruments standardised on the developmental age population and to study
      some of the most frequently impaired cognitive functions in epilepsy.

PMID- 17205224
TI  - Comparative analysis of visual and semi-quantitative assessment of striatal
      [123I]FP-CIT-SPET binding in Parkinson's disease.
AB  - We used qualitative visual assessment and semiquantitative measures of striatal
      DAT binding using [(123)I]FP-CIT-SPET in 85 patients with Parkinson's disease
      (PD). We compared these two assessments and their correlation with PD clinical
      progression. SPET imaging was visually classified by a nuclear medicine physician
      as normal or abnormal pattern grade I, II and III, in relation to a different
      degree of radioligand reduction uptake. Nineteen patients presented abnormal
      grade I (group 1), 53 grade II (group 2) and 13 grade III (group 3). The UPDRS
      III motor score, the H-Y score, the rigidity and bradykinesia subscores were
      significantly different among the three groups. Post hoc analysis showed that all
      values of these clinical parameters were higher in group 3 than in 2 and 1. All
      clinical indices were also significantly higher in group 2 than in group 1. This
      means that groups 3 and 2 were clinically more severely affected. No significant
      differences among the 3 groups were observed for age or duration of disease.
      Values of the mean striatum uptake were also significantly different among the
      three groups. Post hoc analysis revealed significantly lower values of the mean
      striatum uptake in group 3 with respect to groups 2 and 1; values were also
      significantly lower in group 2 than in group 1. We conclude that our findings of
      good consistency between visual and semi-quantitative assessment may help
      simplify the evaluation of striatal DAT binding in PD in a clinical routine
      setting.

PMID- 17205225
TI  - A self-administered questionnaire of ulnar neuropathy at the elbow.
AB  - We report a new self-administered questionnaire for assessment of symptom
      severity of ulnar neuropathy at the elbow (UNE). The new UNE and Levine's
      questionnaires were administered to a sample of UNE subjects and for comparison
      also to a sample of subjects with carpal tunnel syndrome (CTS). We enrolled 89
      consecutive patients (32 women, 57 men, mean age 52.3 years) with UNE and 203
      consecutive patients (157 women and 46 men, mean age 53.7 years) with CTS. The
      protocol of the study consisted in self-administration of the new UNE and
      Levine's questionnaires, as well as scoring of clinical and electrophysiological
      severity of entrapment syndromes with ordinal scales. The UNE questionnaire
      (UNEQ) includes nine questions and considers numbness and tingling in the fourth
      and fifth fingers, elbow pain and modification of pain and paraesthesia with
      elbow position. A score from 1 (absence of symptom) to 5 (most severe) is
      assigned for each question. The overall score is calculated as the mean of the
      nine scores. Test-retest reliability, internal consistency and validity were
      assessed. Responsiveness was also tested in a sample of patients undergoing
      conservative treatment. The UNEQ was reproducible. Spearman's correlation
      coefficient between scores at successive observations (test-retest reliability),
      assessed in the first 44 patients, was 0.97 and Cohen coefficients kappa for
      single items were between 0.64 and 0.81. Internal consistency was high:
      Cronbach's alpha, which summarises interitem correlations among all items of
      UNEQ, was 0.87. Validity was demonstrated by a direct correlation with UNE
      clinical and electrophysiological severity scores (0.65 and 0.35). On the
      contrary, Spearman's correlation coefficients between UNEQ and clinical and
      electrophysiological CTS severity scores were low (0.11 and 0.02, respectively).
      Responsiveness was calculated at 6-8 months follow-up in 25 cases. The effect
      size was 0.46. The Wilcoxon rank-test showed significant improvement between
      basal and follow-up UNEQ scores (Z=-2.39, p=0.017), but not Boston Questionnaire
      scores. There was also significant correlation between UNEQ changes and an
      arbitrary scale of patient satisfaction at follow-up (r=0.85, p<0.001). The UNEQ
      is reproducible, internally consistent and valid. Although further studies are
      required to test its responsiveness to clinical changes, UNEQ may be also
      considered responsive. UNEQ can be used to measure subjective discomfort in UNE
      patients.

PMID- 17205226
TI  - Primary postural instability: a cause of recurrent sudden falls in the elderly.
AB  - Elderly patients with recurrent falls are frequently diagnosed with an
      extrapyramidal syndrome. This study aims to characterise a distinct group of
      patients with recurrent falls and postural instability as a hallmark of the
      clinical examination. The study took place in the Movement Disorders Unit, Rabin
      Medical Center, Petah Tiqva, Israel among 26 patients with recurrent falls who
      had no clinical evidence of a neurodegenerative disease. Medical records,
      neurological examination and brain imaging studies were assessed. Falls in these
      patients were sudden, unprovoked, with no vertigo or loss of consciousness. All
      had postural instability with minimal or no abnormality on the neurological
      examination. Brain imaging showed diffuse ischaemic changes in 65%. [(123)I]
      FPCIT SPECT with the dopamine transporter ligand, performed in five patients, was
      normal in all. Recurrent falls might be caused by a neurological syndrome that
      primarily affects balance control. The importance of identifying this disorder is
      its distinction from other parkinsonian syndromes causing falls.

PMID- 17205227
TI  - Variables influencing quality of life and disability in Charcot Marie Tooth (CMT)
      patients: Italian multicentre study.
AB  - The purpose of this study was to assess the variables that influence quality of
      life (QoL) and disability in patients with Charcot-Marie-Tooth disease (CMT). We
      performed a prospective multicentre study using validated clinical disability and
      QoL measurements. Multivariate analysis was performed using QoL as a dependent
      variable and duration of symptoms, age, gender and CMT type, depression and
      disability measurements as independent variables. We enrolled 211 patients. QoL
      was highly significantly deteriorated with respect to the Italian normative
      sample. The physical aspect of QoL was mainly related to disability but it does
      not increase with the age, probably because of an adaptation between expectation
      and reality. The mental QoL is influenced by depression (hence we have to
      consider this aspect approaching CMT patients). Moreover, we observed that women
      complained of more severe symptoms than men. Finally, some CMT subtypes are
      related to more severe bodily pain symptoms than others. Multiperspective
      assessment of CMT showed new aspects of this disease, mainly regarding (1)
      differences between men and women and (2) the crucial role of pain and
      depression.

PMID- 17205228
TI  - A case of recurrent Miller Fisher syndrome mimicking botulism.
AB  - Miller Fisher syndrome (MFS) is a rare and usually monophasic
      polyradiculoneuropathy characterised by ophthalmoplegia, decreased or absent
      tendon reflexes, and ataxia. The objective of this study was to report a case of
      recurrent MFS with a clinical presentation virtually indistinguishable from
      botulism. The patient was a young man with two episodes of increasing external
      ophthalmoplegia, ptosis, and ataxia with a long asymptomatic interval in between.
      The second episode occurred after consumption of rotten fish and was accompanied
      by gastrointestinal symptoms and an anticholinergic syndrome. Very rarely, MFS
      can present with a recurrent course. The importance of this case of recurrent MFS
      lies not only in its long asymptomatic period and identical clinical
      presentation, but also in its instructiveness regarding the differential
      diagnosis of MFS, particularly life-threatening botulism.

PMID- 17205229
TI  - Nail aplasia, microcephaly, severe mental retardation and MRI abnormalities:
      report of two unrelated cases.
AB  - We present the clinical and laboratory features of two unrelated mentally
      retarded females with sporadic bilateral periventricular nodular heterotopia
      (BPNH), hypoplastic/absent nails and other malformative features. Clinical
      examination, MRI scanning, EEG recording, karyotyping and neuropsychological
      testing were performed. From a molecular genetic point of view, direct sequencing
      analysis, X-inactivation assay and telomere analysis were carried out in one
      patient. The two patients showed convincing similarities from clinical and
      neuroradiological points of view with BPNH, mental retardation, microcephaly and
      hypoplastic/absent nails of fingers and toes. Our two unrelated mentally retarded
      females may be affected by complex malformative syndromes sharing some common
      features such as BPNH, mental retardation and hypoplastic/absent nails. Further
      genetic studies are needed to better understand the pathogenetic bases of this
      neurological disease. These two cases widen the spectrum of BPNH-associated
      syndromes.

PMID- 17205230
TI  - Concurrent relapsing central nervous system and ocular involvement in a case of
      life-threatening Adamantiades-Behcet Disease (ABD).
AB  - Adamantiades-Behcet disease (ABD) is characterised by oral and genital
      ulcerations, skin lesions and ocular manifestations and, rarely, by central
      nervous system (CNS) involvement. Neuro-Behcet disease (NBD) is categorised to
      parenchymal or non-parenchymal, while combined CNS disease is rarely reported in
      the literature. A case of NBD, with severe relapsing ocular and neurological
      disease of combined pattern is presented. Neurological complications included
      brainstem manifestations, as well as neurovascular involvement, while ocular
      involvement consisted of bilateral uveitis and branch retinal vein occlusion.
      Manifestations responded to corticosteroid plus cyclophosphamide pulse therapy.
      Maintenance therapy included cyclosporine A, azathioprine and corticosteroids.
      Case individualities are discussed, focusing on scepticism concerning treatment
      of NBD relapses in the long term.

PMID- 17205231
TI  - Non-convulsive status epilepticus and generalised tonic-clonic seizures
      persisting in old age in a patient with idiopathic generalised epilepsy: a long
      term observation.
AB  - Persisting non-convulsive status epilepticus in a man with idiopathic generalised
      epilepsy is reported. After a first generalised tonic/clonic seizure on awakening
      one day at the age of 20, the patient experienced rare non-convulsive status
      epilepticus until the age of 73, when the frequency of the episodes increased, in
      spite of the initiation of treatment with antiepileptic drugs. No significant
      cognitive decline was documented when the patient was 83. The existence of such
      conditions in the context of idiopathic generalised epilepsy shows the problems
      of syndromic diagnosis and of age dependency of some epileptic phenomena over the
      course of life with potential bidirectional influences between epileptic
      manifestations and senile processes.

PMID- 17205232
TI  - Hemichorea associated with polycythaemia vera.
AB  - Chorea is a rare complication of polycythaemia vera. Polycythaemic chorea occurs
      predominantly in females and usually in generalised form. We present a 66-year
      old woman with acute onset hemichorea-ballism with no vascular pathology in the
      basal ganglia region. A clear relationship was observed between the onset of
      chorea and worsening of haematological parameters in the patient. After repeated
      phlebotomies the patient's clinical status was improved. Polycythaemic chorea
      must be considered, especially in the elderly, as early diagnosis leads to
      effective treatment and prevention of complications.

PMID- 17205233
TI  - Post-malaria neurological syndrome: clinical and laboratory findings in one
      patient.
AB  - Post-malaria neurological syndrome (PMNS) is a rare complication of malaria. It
      follows recovery from an episode of Plasmodium falciparum malaria and is
      characterised by symptoms and signs of encephalopathy. Patients usually improve
      without any specific treatment. The pathogenesis is unknown, but it is probably
      immunologically mediated. The objective of this case study is to describe the
      first Italian patient with PMNS. A 60-year-old Italian man developed acute P.
      falciparum malaria after a stay in French Guinea. Twenty days after recovering
      from malaria, he became confused, developed generalised weakness, limb tremors,
      shivering and dizziness. These symptoms continued for three days, then resolved
      spontaneously. Neuroimaging was normal. Cerebrospinal fluid analysis revealed
      breakdown of the blood/brain barrier, without oligoclonal bands and normal IgG
      index. Our patient presented a mild diffuse encephalopathy suggestive of a
      generic activation of the immune system without any specific reaction against
      antigens within the CNS.

PMID- 17205234
TI  - Inter-coder agreement for ICD-9-CM coding of stroke.
AB  - The objective was to evaluate agreement among neurologists for coding stroke,
      using the International Classification of Diseases 9th Revision - Clinical
      Modification (ICD-9-CM). Clinical records of 53 consecutive patients (27 stroke
      or TIA and 26 other diseases) discharged from our general neurology department
      were coded by four neurology residents, four general neurologists and four
      neurologists trained in ICD-coding (experts). Inter-coder agreement was evaluated
      by the kappa statistic. The overall kappa value for coding 430-438 was 0.77 (95%
      confidence interval 0.70-0.84) for primary (PDx) and 0.82 (0.77-0.88) for
      PDx+secondary diagnoses (SDx). It was 0.73-0.86 for the residents, 0.78-0.90 for
      the neurologists and 0.67-0.88 for the experts. The overall kappa values (PDx,
      SDx) for specific codes were 0.83-0.88 for 431-intracerebral haemorrhage
      (residents: 0.75-0.89; neurologists: 0.91-0.96; experts: 0.78-0.88) and 0.48-0.51
      for 434-occlusion of cerebral arteries) (residents: 0.26-0.26; neurologists: 0.61
      0.66; experts: 0.60-0.65). Agreement was substantial for the whole code group 430
      438 and higher for code 431 than 434. Reliability was generally improved when
      both PDx and SDx were considered. Specific training did not increase inter
      coders' agreement.

PMID- 17205235
TI  - Antonio Berti and the early history of aphasia in Italy.
AB  - Whilst the debate about cerebral localisation of articulate speech was raging in
      France in the 1860s and in particular with reference to the observations of Paul
      Broca, there were also some Italians who attempted to make a contribution on the
      subject. Among those was the physician Antonio Berti, who in 1865 furnished some
      interesting observations on the association of aphasia with the frontal lobe. In
      this paper we intend to revive this forgotten episode that represents one of the
      early Italian observations on the issue of cortical localisation of speech.

PMID- 17205237
TI  - A comparison of commercially available demineralized bone matrix for spinal
      fusion.
AB  - In an effort to augment the available grafting material as well as to increase
      spinal fusion rates, the utilization of a demineralized bone matrix (DBM) as a
      graft extender or replacement is common. There are several commercially available
      DBM substances available for use in spinal surgery, each with different amounts
      of DBM containing osteoinductive proteins. Each product may have different
      osteoinductivity potential due to different methods of preparation, storage, and
      donor specifications. The purpose of this study is to prospectively compare the
      osteoinductive potential of three different commercially available DBM substances
      in an athymic rodent spinal fusion model and to discuss the reasons of the
      variability in osteoinductivity. A posterolateral fusion was performed in 72
      mature athymic nude female rats. Three groups of 18 rats were implanted with 1 of
      3 DBMs (Osteofil, Grafton, and Dynagraft). A fourth group was implanted with
      rodent autogenous iliac crest bone graft. The rats were sacrificed at 2, 4, 6,
      and 8 weeks. A dose of 0.3 cm(3) per side (0.6 cm(3)per animal) was used for each
      substance. Radiographs were taken at 2 weeks intervals until sacrifice. Fusion
      was determined by radiographs, manual palpation, and histological analysis. The
      Osteofil substance had the highest overall fusion rate (14/18), and the highest
      early 4 weeks fusion rate of (4/5). Grafton produced slightly lower fusion rates
      of (11/17) overall, and lower early 4 weeks fusion rate of (2/5). There was no
      statistically significant difference between the rate of fusion after
      implantation of Osteofil and Grafton. None of the sites implanted with Dynagraft
      fused at any time point (0/17), and there was a significantly lower fusion rate
      between the Dynagraft and the other two substances at the six-week-time point and
      for final fusion rate (P = 0.0001, Fischer's exact test). None of the autogenous
      iliac crest animals fused at any time point. Non-decalcified histology confirmed
      the presence of a pseudarthrosis or the presence of a solid fusion, and the
      results were highly correlated with the manual testing. Although all products
      claim to have significant osteoinductive capabilities, this study demonstrates
      that there are significant differences between some of the tested products.

PMID- 17205239
TI  - Total lumbar disc replacement in athletes: clinical results, return to sport and
      athletic performance.
AB  - Despite the increasing popularity of total lumbar disc replacement (TDR) in
      predominantly young and active patients, no previous study has addressed
      possibilities, limitations and potential risks regarding athletic performance
      following TDR. Mechanical concerns remain and the implant's resilience as regards
      its load-bearing capacity during sporting activities is unknown. Thirty-nine
      athletic patients fulfilled the inclusion criteria for this study. These patients
      participated in a large variety of different types of sport. Significant and
      lasting pain-relief was attained following TDR with a mean follow-up of 26.3
      months (range 9-50.7 months; FU rate 97.4%). Sporting activity was resumed within
      the first 3 months (38.5%) to 6 months (30.7%) with peak performance being
      reached after 5.2 months. Thirty-seven patients (94.9%) achieved resumption of
      sporting activity. Athletic performance improved significantly in 33 patients
      (84.6%). Minor subsidence was observed in 13 patients (30%) within the first 3
      months with no further implant migration thereafter in 12 patients. Participation
      in all types of sport recorded in this study was accessible for a high rate of
      patients up to the level of professional athletes as well as those participating
      in extreme sports. Preoperative participation in sport proved to be a strong
      positive predictor for highly satisfactory postoperative outcome following TDR.
      In a selected group of patients, however, preoperative inability to participate
      in sporting activities did not impair postoperative physical activity. Due to the
      young age of the patients and significant load increase exerted during athletic
      activities, persisting concerns regarding the future behaviour of the implant
      remain and will require longer follow-up, modified investigation techniques and
      larger patient cohorts.

PMID- 17205240
TI  - Biomechanical study of anterior spinal instrumentation configurations.
AB  - The biomechanical impact of the surgical instrumentation configuration for spine
      surgery is hard to evaluate by the surgeons in pre-operative situation. This
      study was performed to evaluate different configurations of the anterior
      instrumentation of the spine, with simulated post-operative conditions, to
      recommend configurations to the surgeons. Four biomechanical parameters of the
      anterior instrumentation with simulated post-operative conditions have been
      studied. They were the screw diameter (5.5-7.5 mm) and its angle (0 degrees -
      22.5 degrees), the bone grip of the screw (mono-bi cortical) and the amount of
      instrumented levels (5-8). Eight configurations were tested using an experimental
      plan with instrumented synthetic spinal models. A follower load was applied and
      the models were loaded in flexion, torsion and lateral bending. At 5 Nm, average
      final stiffness was greater in flexion (0.92 Nm/degrees) than in lateral bending
      (0.56 Nm/degrees) and than in torsion (0.26 Nm/degrees). The screw angle was the
      parameter influencing the most the final stiffness and the coupling behaviors. It
      has a significant effect (p < or = 0.05) on increasing the final stiffness for a
      22.5 degrees screw angle in flexion and for a coronal screw angle (0 degrees) in
      lateral bending. The bi-cortical bone grip of the screw significantly increased
      the initial stiffness in flexion and lateral bending. Mathematical models
      representing the behavior of an instrumented spinal model have been used to
      identify optimal instrumentation configurations. A variation of the angle of the
      screw from 22.5 degrees to 0 degrees gave a global final stiffness diminution of
      13% and a global coupling diminution of 40%. The screw angle was the most
      important parameter affecting the stiffness and the coupling of the instrumented
      spine with simulated post-operative conditions. Information about the effect of
      four different biomechanical parameters will be helpful in preoperative
      situations to guide surgeons in their clinical choices.

PMID- 17205241
TI  - Medium-term survival without haematopoietic stem cell transplantation in a case
      of IPEX: insights into nutritional and immunosuppressive therapy.

PMID- 17205242
TI  - Perioperative extracorporeal membrane oxygenation support for critical pediatric
      airway surgery.
AB  - Extracorporeal membrane oxygenation (ECMO) has been used for cardiopulmonary
      support in neonates, infants, and adults. We report the application of ECMO for
      critical airway surgery when mechanical ventilation cannot provide adequate gas
      exchange. Three pediatric patients underwent emergency ECMO establishment because
      of hypercapnia that could not be managed by conventional mechanical ventilation.
      The pathology included: (1) left pulmonary artery sling with long-segment
      tracheal stenosis; (2) absence of the right intermediate bronchus and abnormal
      origin of the right lower bronchus arising from the left main bronchus; (3) right
      lung agenesis with long-segment tracheobronchial stenosis. Venoarterial ECMO was
      established. Before ECMO, the arterial pH values were 7.28, 7.0, and 7.08, and
      the PaCO2 values were 111.8, 112.0, and 208.7 mmHg for each patient,
      respectively. After ECMO support, respiratory acidosis was reversed. The patients
      then underwent surgical intervention. The surgical procedures included: (1) slide
      tracheoplasty and reimplantation of the left pulmonary artery; (2) resection of
      the stenotic tracheal segment and reconstruction of the bronchial tree; (3)
      tracheal dilatation and stent implantation. The ECMO durations were 11, 5, and 16
      h, respectively. All patients were successfully weaned off ECMO without
      complications. In conclusion, ECMO provided adequate ventilation support for
      patients undergoing critical tracheobronchial reconstruction when conventional
      mechanical ventilation could not maintain adequate gas exchange.

PMID- 17205243
TI  - Inhaled nitric oxide therapy during the transport of neonates with persistent
      pulmonary hypertension or severe hypoxic respiratory failure.
AB  - Our aim was to determine whether starting inhaled nitric oxide (iNO) on
      critically ill neonates with severe hypoxemic respiratory failure and/or
      persistent pulmonary hypertension (PPH), at a referring hospital at the start of
      transport, decreases the need for extracorporeal membrane oxygenation (ECMO),
      lessens the number of hospital days and improves survival in comparison with
      those patients who were started on iNO only at the receiving facility. The study
      was a retrospective review of 94 charts of neonates that had iNO initiated by the
      transport team at a referring hospital or only at the tertiary neonatal intensive
      care unit (NICU) of the receiving hospital. Data collected included demographics,
      mode of transport, total number of hospital days, days on inhaled nitric oxide
      and ECMO use. Of the 94 patients, 88 were included. Of these, 60 were started on
      iNO at the referring facility (Field-iNO) and 28 were started at the receiving
      NICU (CHLA-iNO). All patients survived transport to the receiving NICU. Death
      rates and ECMO use were similar in both groups. Overall, patients who died were
      younger and had lower birth weights and Apgar scores. For all surviving patients
      who did not require ECMO, the length of total hospital stay (median days 22
      versus 38, P = 0.018), and the length of the hospital stay at the receiving
      hospital (median days 18 versus 29, P = 0.006), were significantly shorter for
      the Field-iNO patients than for the CHLA-iNO patients, respectively. Earlier
      initiation of iNO may decrease length of hospital stay in surviving neonates with
      PPH not requiring ECMO.

PMID- 17205244
TI  - Prognosis of antenatally diagnosed oligohydramnios of renal origin.
AB  - Although clinical outcome data on fetuses with oligohydramnios of renal origin
      are scarce, prognosis is regarded as poor due to a high risk of renal dysfunction
      and pulmonary hypoplasia. This review aims to summarize the current knowledge and
      clinical experience with patients presenting antenatally with renal
      oligohydramnios. By reviewing the underlying mechanisms, complications, and
      outcome data, we hope to further improve antenatal counseling and postnatal care.
      We conclude that prognosis of ROH has changed in recent years. While early data
      before the introduction of sophisticated neonatal intensive care and renal
      replacement therapy indicated a poor prognosis, nowadays, a much more optimistic
      prognosis of children after renal oligohydramnios can be expected from the recent
      publications in the literature.

PMID- 17205245
TI  - Sedation and analgesia for brief diagnostic and therapeutic procedures in
      children.
AB  - The number of diagnostic and therapeutic procedures done outside of the operating
      room and the intensive care unit has increased substantially in recent years. In
      parallel, the management of acute pain and anxiety in children undergoing
      therapeutic and diagnostic procedures has developed considerably in the past two
      decades. The primary goal of procedural sedation and analgesia is the safe and
      efficacious control of emotional distress and pain. The availability of non
      invasive monitoring, short-acting opioids and sedatives has broadened the
      possibilities of sedation and analgesia in children in diverse settings. While
      most of these procedures themselves pose little risk to the child, the
      administration of sedation or analgesia may add substantial risk to the patient.
      This article reviews the current status of sedation and analgesia for invasive
      and non-invasive procedures in children providing an evidence-based approach to
      several topics of importance, including patient assessment, personnel
      requirements, equipment, monitoring, and drugs.

PMID- 17205246
TI  - Does the surface structure of implants have an impact on the formation of a
      capsular contracture?
AB  - BACKGROUND: The formation of a fibrous capsule around a silicone breast implant
      is part of a physiologic foreign body reaction after breast augmentation. In
      contrast, the formation of a capsular contracture is a local complication of
      unknown cause. This study aimed to discover whether the surface structure of the
      implant (textured vs smooth) has any impact on the formation of a capsular
      contracture. METHODS: This prospective study included 48 female patients with
      unilateral capsular fibrosis grades 1 to 4 in Baker's clinical scaling system. Of
      these patients, 14 received implants with a textured surface (Mentor), and 34
      received implants with a smooth surface (Mentor). The implants all were placed in
      a submuscular position by the same experienced plastic surgeon. The clinical data
      were assessed using standardized patient questionnaires. For histologic
      diagnosis, operatively excised capsular tissue was examined. Preoperatively,
      venous blood samples for determining serum hyaluronan concentrations were taken
      from the patients. The control group consisted of 20 patients without capsular
      fibrosis. RESULTS: The separate analysis of clinical data for the patients with
      textured and those with smooth-surfaced breast implants showed a slightly reduced
      degree of symptoms for the patients with textured silicone breast implants, as
      compared with those who had smooth-surfaced implants. The histologic assessment
      of the fibrosis showed a symmetric distribution for Wilflingseder scores 1 to 3
      (29% each), whereas 13% of the capsular tissues could be assigned to
      Wilflingseder score 4. In contrast, the histologic assessment of the patients
      with smooth-surfaced implants predominantly showed a Wilflingseder score of 3
      (65%). The serologic investigations via enzyme-linked immunoassay (ELISA) showed
      serum hyaluronan concentrations of 10 to 57 ng/ml (25.0 +/- 11.7 ng/ml).
      Therefore, no statistically significant differences in terms of serum hyaluronan
      levels could be determined between the two groups of patients. In comparison with
      the control group, the patients with implants showed elevated serum hyaluronan
      levels (p < 0.05). CONCLUSIONS: The histologic examination and serum hyaluronan
      concentration analysis showed no statistically significant difference between
      smooth-surfaced and textured implants (Mentor) with respect to the development of
      capsular contracture. On the other hand, the severity of capsular contracture
      showed a positive linear correlation with the degree of local inflammatory
      reactions, which were independent of the implant surface.

PMID- 17205247
TI  - A new scalpel for circular incisions: compass scalpel.

PMID- 17205248
TI  - Modified device for easy infiltration of tumescent solution in liposuction.
AB  - BACKGROUND: Managing large amounts of tumescent fluid may be cumbersome and a
      waste of time. To solve the problems of an easy, quick, reliable, and cost
      effective jet infiltration technique for large tumescent volumes, the authors
      describe a simple handpiece that connects with standard air-driven wound
      irrigation systems. On the basis of former observations with a modified
      irrigation system previously published by our group, a newly developed multi-use
      irrigation infiltration cannula handpiece was used successfully for 63 patients
      without any complications. METHODS: An infiltration cannula with a handpiece and
      standard luer lock adapter that connects with an air-driven wound irrigation
      system required for liposuction procedures was developed and clinically tested.
      RESULTS: Between 2003 and 2005, a total of 63 patients with moderate- to large
      volume suction (1,500-4,500 ml) were treated by subcutaneous infiltration of
      tumescent solution using the air-driven irrigation system and the newly developed
      infiltration cannula. The device proved to be reliable and efficient. No
      disconnection of the system was seen. The time savings and ease of use were most
      noticeable in cases of larger volume infiltration. Wiring and tubing of this
      device was facilitated in any case. No adverse side effects were noted.
      CONCLUSION: A simple infiltration cannula system that connects with standard
      wound irrigation systems facilitates the liposuction procedure in terms of cost
      effectiveness and time savings.

PMID- 17205249
TI  - Bilateral reduction mammaplasty for immediate breast conservation surgery
      reconstruction and intraoperative radiotherapy: a preliminary report.
AB  - BACKGROUND: Breast conservation surgery and postoperative radiotherapy are widely
      accepted as the treatment of choice for patients with early breast cancer.
      Despite its oncologic benefits, the radiotherapy may cause unpredictable outcomes
      in soft tissues, especially in patients undergoing breast reconstruction.
      Described recently, intraoperative irradiation (IORT) has been indicated for
      selected patients as an alternative to radiotherapy with fewer adverse local
      effects. Clinical use of reduction mammaplasty (RM) techniques in oncologic
      breast surgery has been described previously. However, no previous studies have
      mentioned its application after breast conservation surgery and IORT. METHODS:
      The authors used RM to reconstruct a partial breast tissue defect secondary to
      breast conservation surgery followed by IORT treatment in a 46-year-old patient
      with an 11-mm invasive ductal carcinoma between the superior internal quadrants
      of the right breast. RESULTS: Satisfactory breast volume and shape were achieved,
      and no immediate or late complications were observed. After 2 postoperative
      years, no evidence of fat necrosis, tumor recurrence, or tissue volume loss was
      observed. CONCLUSION: The initial data indicate that RM in the setting of breast
      conservation surgery reconstruction and IORT is feasible. With appropriate
      patient selection, respecting indications and limitations, RM has its place among
      the various reconstructive techniques. Additional studies with larger clinical
      series and longer follow-up periods are necessary to analyze the precise IORT
      effects in patients submitted to immediate breast conservation surgery
      reconstruction.

PMID- 17205250
TI  - Histologic findings in axillary hydradenosuction.
AB  - Liposuction or its modifications have become accepted therapy for hyperhidrosis.
      During the nearly 20 years since its introduction, the actual anatomic removal of
      sweat glands has not been investigated. In this study, three patients underwent
      axillary liposuction and histologic examination of the aspirates. Apocrine sweat
      glands embedded in adipose tissue were found throughout the crosscuts. These
      results prove that the therapeutic effects are at least partially attributable to
      removal of glandular tissue.

PMID- 17205251
TI  - Postoperative analgesic effect of locally infiltrated levobupivacaine in fleur-de
      Lys abdominoplasty.
AB  - BACKGROUND: This prospective double-blind study compared the analgesic properties
      of locally infiltrated levobupivacaine with those of ropivacaine in fleur-de-lys
      abdominoplasty. METHODS: A total of 46 patients subjected to fleur-de-lis
      abdominoplasty under general anesthesia were included. The patients were randomly
      assigned to receive local infiltration of the peri-incisional and dissected area
      with the following solutions: group A (placebo group, n = 15) received 100 ml of
      saline 0.9%, group B (n = 15) received 50 ml of ropivacaine 0.75% in 50 ml of
      saline 0.9%, and group C (n = 16) received 60 ml of levobupivacaine 0.25% in 40
      ml of saline 0.9%. The anesthetic technique was standardized for all the groups.
      The patients were asked to assess their pain at rest on a visual analog scale
      (VAS) at 2 h, 4 h, and 24 h postoperatively. Data were analyzed by mixed analysis
      of variance (ANOVA), simple ANOVA, and repeated measures ANOVA, followed by
      Tukey's test. RESULTS: Groups B and C did not differ significantly in their VAS
      scores at 2 h postoperatively, but group C experienced significantly less pain (p
      < 0.001) than either the control group or the B group at 4 h and 24 h
      postoperatively. Group B also registered significantly lower VAS scores (p <
      0.001) than the placebo group at 4 h postoperatively. CONCLUSIONS: It is
      concluded that for mini abdominoplasty, adequate analgesia is achieved for at
      least 4 h postoperatively by local tissue infiltration with either ropivacaine or
      levobupivacaine. However, in terms of intensity and duration of analgesia,
      levobupivacaine was found to be more effective than ropivacaine in reducing
      postoperative pain associated with mini abdominoplasty.

PMID- 17205252
TI  - The impact of breast size on the vertebral column: a radiologic study.
AB  - BACKGROUND: Macromastia usually is associated with the physical and psychological
      symptoms reported comprehensively by many studies. Reduction mammoplasty seems to
      be the most reasonable solution for these symptoms, and many articles have
      reported improvement of these complaints after surgery. Some authors have
      postulated that the anatomic mechanisms of postural aberrations are heavy breasts
      and related pain symptoms. However, limited numbers of studies have tried to
      explain the effect of the heavy breasts on the vertebral column. METHODS: This
      study enrolled 100 females in four groups according to their breast cup sizes
      (groups A, B, C, D). All four groups were compared with each other statistically
      using one-way analysis of variance (ANOVA) followed by a post hoc test according
      to the body mass index (BMI) as well as the thoracic kyphosis, lumbar lordosis,
      and sacral inclination angles. RESULTS: The BMI was significantly higher in the D
      cup-sized breast group. There was a statistically significant difference between
      groups A and D in terms of the thoracic kyphosis and the lumbar lordosis angles,
      and between groups B and D in terms of the lumbar lordosis angle. No
      statistically significant difference was detected between the groups in terms of
      the sacral inclination angle. CONCLUSION: Breast size seems to be an important
      factor that affects posture, especially the thoracic kyphosis and lumbar lordosis
      angles.

PMID- 17205253
TI  - A technical refinement to prevent supratip deformity in aesthetic rhinoplasty:
      "the trapezoid peak".
AB  - BACKGROUND: The relationship between appropriate caudal dorsum resection and
      supratip deformity or inadequate tip projection currently is clear. Correct
      quadrangular cartilage management seems to have a basic role in the final tip
      aspect after aesthetic rhinoplasty. METHODS: Primary aesthetic rhinoplasty was
      performed for 38 Caucasian patients. A septal refinement was used for patients
      requiring extra tip support and not requiring grafts. RESULTS: The minimum follow
      up period was 1 year. No supratip deformity was noted after surgery. The tip and
      midvault had adequate projection. CONCLUSIONS: The described maneuver sustains
      the alar cartilage without sutures, preventing supratip deformity, sustaining
      soft tissues, and avoiding loss of tip projection.

PMID- 17205254
TI  - Decision making in abdominoplasty.
AB  - BACKGROUND: Improvements and variations in abdominoplasty techniques have
      complicated patient and procedure selection. The authors describe their
      guidelines for selecting the ideal procedure to be used with patients by
      stratifying them into treatment groups according to the presence and location of
      excess skin and subcutaneous tissue, lipodystrophy, and abdominal wall laxity.
      METHODS: A prospective study analyzed 151 female patients treated for abdominal
      contour deformities from January 2004 to July 2005. The patients were
      systematically classified into five treatment groups: mini-abdominoplasty (5%),
      standard abdominoplasty (42%), abdominoplasty with liposuction and minimal
      midline undermining (10%), standard abdominoplasty with removal of deep fat
      (13%), and circumferential abdominoplasty (30%). RESULTS: The patients had a mean
      age of 42 years and a mean body mass index (BMI) of 26 kg/m(2). The prevalence of
      overweight (BMI, 25.0-29.9) was 37%, and that of obesity (BMI > 30.0) was 19%.
      Comparison of pre- and postoperative photographs included improved tension of the
      entire abdominal wall, enhancement of the waistline, and increased uniformity of
      the contour of the abdomen. There was a significant difference in mean BMI
      between preabdominoplasty (26 kg/m(2)) and postabdominoplasty (24 kg/m(2)) (p =
      0.01). The prevalence of overweight and obesity decreased by 8% and 9%,
      respectively (p = 0.01), and a decrease in BMI occurred within each
      abdominoplasty subgroup (p = 0.01). The prevalence of complications was 11%.
      Seroma (4%) and delayed wound healing (4%) were the most common. One case of
      pulmonary embolus was encountered. Although there was a positive trend in
      complications with higher BMI, no statistically significant difference was found
      (p = 0.74). Half of the patients had additional procedures performed without a
      significant increase in complications (p = 0.5). CONCLUSIONS: The described
      algorithm for abdominoplasty selection is safe, effective, and flexible, with
      long-term improvement in abdominal contour and BMI.

PMID- 17205255
TI  - Follicular transplantation for the correction of various stigmas after
      rhytidoplasty.
AB  - BACKGROUND: Rhytidoplasty may cause permanent and unwanted stigmas, such as
      dislocation of the temporal and cervical hairline. Widened scars inside the
      hairline may cause considerable social embarrassment. Furthermore, pretrichial
      incisions, even if well placed, may widen or become hypochromic, thus revealing
      that an aesthetic procedure has been performed. Various procedures for the
      correction of these undesirable telltale signs of a face-lift have been
      published. This report aims to present the results of correction for
      postrhytidoplasty stigmas using follicular transplantation. Patient assessment is
      discussed, and relevant technical aspects are detailed and illustrated. METHODS:
      A prospective study at the Ivo Pitanguy Clinic investigated patients who
      underwent hair transplantation to correct unaesthetic signs secondary to
      rhytidoplasty from January 2001 to December 2004. The aesthetic results and
      complications were evaluated, as well as the patients' satisfaction rate. The
      patients presented in this series either were referred from another service or
      had their rhytidoplasty originally performed in the authors' service. RESULTS: A
      total of 33 female patients were included in this study. Two patients were lost
      to follow-up evaluation and not included. The complications were minor. In the
      late follow-up assessment, 24 patients classified the result as excellent, 4 as
      satisfactory, and 3 as unsatisfactory. Only the patients who classified the
      results as unsatisfactory requested a second procedure (i.e., another follicular
      transplantation). CONCLUSIONS: When performed by an experienced surgical team,
      the follicular unit transplantation technique is a simple, safe, and efficient
      way to correct stigmas secondary to a rhytidoplasty, such as a visible scar or a
      displaced hairline, with satisfactory results and a very low complication rate.

PMID- 17205256
TI  - Digital photography in plastic surgery: how to achieve reasonable standardization
      outside a photographic studio.
AB  - Accurate photographic documentation has become essential in reconstructive and
      cosmetic plastic surgery both for clinical and scientific purposes. Digital
      imaging systems currently are popular, being reasonably affordable and much
      improved in quality. They offer multiple advantages in terms of quality, easy
      image storage and retrieval. Nevertheless, obtaining standardized, consistent,
      and relevant digital images is not easy outside a photographic studio. The
      purpose of this report is to define guidelines for accurate image capture in
      different anatomic areas, following elementary general criteria based on
      practical issues beyond the purely theoretical, to obtain reasonable
      standardization, consistency, and reproducibility.

PMID- 17205257
TI  - Treatment of muscular pseudogynecomastia with botulinum toxin A.

PMID- 17205258
TI  - Air drainage: an essential technique for preventing breast augmentation-related
      pneumothorax.
AB  - BACKGROUND: Pneumothorax is one of the most poorly understood and least
      frequently reported complications associated with breast augmentation, yet this
      complication presents as a dramatic and often extremely distressing event to both
      the patient and the surgeon. In addition, this complication is associated with an
      estimated 10% occurrence of medicolegal consequence. A recent survey of 363
      Californian Plastic Surgeons concerning the occurrence and outcome of breast
      augmentation related Pneumothorax suggested that the incidence of this
      complication could be more prevalent than previously reported. The author
      previously suggested barotrauma as the underlying mechanism responsible for the
      development of pneumothorax associated with breast augmentation. This study aimed
      to analyze the role of air drainage in preventing pneumothorax during insertion
      of breast implants. METHODS: A control group of five patients who experienced
      pneumothorax was compared with a group of six consecutive patients whose surgical
      pocket was drained of air during insertion of the implant. RESULTS: None of the
      study patients experienced pneumothorax. CONCLUSIONS: Air drainage from the
      surgical cavity during insertion of the implant is extremely successful in
      preventing the development of breast augmentation-related pneumothorax. It is
      suggested that air drainage be introduced as a routine step in breast
      augmentation procedures, particularly in those that involve insertion of large
      implants through small incisions.

PMID- 17205259
TI  - Dermolipectomy of the pubic area associated with abdominoplasty.
AB  - Aesthetic alterations of the pubic area, whether constitutional or the result of
      excessive weight, if not treated, may become more evident after an
      abdominoplasty. The authors recommend a simple and effective technique to be
      performed simultaneously with abdominoplasty that leads to satisfactory results
      and does not interfere with the lymphatic drainage of the area.

PMID- 17205260
TI  - Ordered adsorption of coagulation factor XII on negatively charged polymer
      surfaces probed by sum frequency generation vibrational spectroscopy.
AB  - Electrostatic interactions between negatively charged polymer surfaces and factor
      XII (FXII), a blood coagulation factor, were investigated by sum frequency
      generation (SFG) vibrational spectroscopy, supplemented by several analytical
      techniques including attenuated total reflection Fourier transform infrared
      spectroscopy (ATR-FTIR), quartz crystal microbalance (QCM), zeta-potential
      measurement, and chromogenic assay. A series of sulfonated polystyrenes (sPS)
      with different sulfonation levels were synthesized as model surfaces with
      different surface charge densities. SFG spectra collected from FXII adsorbed onto
      PS and sPS surfaces with different surface charge densities showed remarkable
      differences in spectral features and especially in spectral intensity.
      Chromogenic assay experiments showed that highly charged sPS surfaces induced
      FXII autoactivation. ATR-FTIR and QCM results indicated that adsorption amounts
      on the PS and sPS surfaces were similar even though the surface charge densities
      were different. No significant conformational change was observed from FXII
      adsorbed onto surfaces studied. Using theoretical calculations, the possible
      contribution from the third-order nonlinear optical effect induced by the surface
      electric field was evaluated, and it was found to be unable to yield the SFG
      signal enhancement observed. Therefore it was concluded that the adsorbed FXII
      orientation and ordering were the main reasons for the remarkable SFG amide I
      signal increase on sPS surfaces. These investigations indicate that negatively
      charged surfaces facilitate or induce FXII autoactivation on the molecular level
      by imposing specific orientation and ordering on the adsorbed protein molecules.

PMID- 17205261
TI  - Validation of a new planar chromatographic method for quantification of the
      heterocyclic aromatic amines most frequently found in meat.
AB  - A new HPTLC method, in which all the HPTLC steps are performed automatically, has
      been established for quantification of the five most frequently found
      heterocyclic aromatic amines (HAA: PhIP, MeIQx, 4,8-DiMeIQx, norharmane, and
      harmane). The method was used for trace analysis (low microg kg(-1) range) of HAA
      in meat samples and found to be a cost-effective alternative to HPLC, because it
      enables simultaneous chromatography of up to 20 samples within 30 min. After
      preconditioning of the HPTLC silica gel layer with ammonia vapour the plate was
      developed with methanol-chloroform, 1:9 (v/v). At least 4o separations were
      obtained and selectivity for the meat matrix was achieved. In repeatability tests
      relative standard deviations (RSD, n = 14, peak height) were less than or equal
      to +/-3.3%. In tests of intermediate precision (mean value for 14 tracks on six
      different plates on six different days) RSDs were better than +/-2% (peak
      height). Measurement of the reproducibility of migration distances on six
      different plates resulted in RSDs less than or equal to +/-1.3%. Limits of
      detection and quantification (S/N 3 and 10, respectively) for the five HAA ranged
      between 0.4 and 5 ng per band and between 0.8 and 14 ng per band, respectively.
      With paraffin-n-hexane, 3:7 (v/v), as fluorescence enhancer more sensitive
      determinations (up to 8.5-fold greater signal intensities) were achieved for
      PhIP, norharmane, and harmane. In the working range (1:10) polynomial regressions
      for PhIP, MeIQx, and 4,8-DiMeIQx and linear regressions for norharmane and
      harmane resulted in RSDs between +/-1.9 and 3.6%. To confirm the absence of
      potentially coeluting minor HAA, rarely formed in meat, mass spectra were
      occasionally recorded by online ESI-MS. Robustness tests showed that
      preconditioning with ammonia was essential for successful separation and that
      relative humidity had only a minor effect on the chromatography.

PMID- 17205262
TI  - Trends in human risk assessment of pharmaceuticals.

PMID- 17205263
TI  - CH-overtone regions as diagnostic markers for near-infrared spectroscopic
      diagnosis of primary cancers in human pancreas and colorectal tissue.
AB  - We have investigated the application of near-infrared spectroscopy for detection
      of human primary pancreatic and colorectal cancers. Spectra from cancerous and
      normal tissue were collected from a total of 37 surgically resected pancreatic
      and colorectal patient tissue specimens using a fibre-optic probe. Major spectral
      differences were observed in the CH-stretching first (6,000-5,400 cm(-1)) and
      second overtone (9,000-7,900 cm(-1)) regions. By use of artificial neural
      networks, linear discriminant analysis, and cluster analysis as pattern
      recognition methods the spectra were classified into cancerous and normal tissue
      groups with accuracy up to 89%. We also explored differences between the spectra
      obtained from colorectal and pancreatic tissue. Spectral data from cancerous and
      normal tissue were classified organ-specifically into four groups with accuracy
      between 80 and 83%. Our results indicate that CH-overtone regions, besides
      serving as diagnostic markers for NIR spectroscopic diagnosis of primary human
      pancreas and colorectal cancers, are also useful for elucidating differences
      between the spectra obtained from colorectal and pancreatic cancerous tissue.

PMID- 17205264
TI  - Feasibility of gamma irradiation as a stabilisation technique in the preparation
      of tissue reference materials for a range of shellfish toxins.
AB  - The effect of gamma-irradiation on concentrations of hydrophilic and lipophilic
      phycotoxins has been investigated by use of HPLC-UV and LC-MS. Pure toxins in
      organic solvents and toxins in mussel (Mytilus edulis) tissues were irradiated at
      three different doses. In solution all toxin concentrations were reduced to some
      extent. Most severe decreases were observed for domoic acid and yessotoxin, for
      which the smallest dose of irradiation led to almost complete destruction. For
      pectenotoxin-2 the decrease in concentration was less severe but still continuous
      with increasing dose. Azaspiracid-1 and okadaic acid were the least affected in
      solution. In shellfish tissue the decrease in toxin concentrations was much
      reduced compared with the effect in solution. After irradiation at the highest
      dose reductions in concentrations were between ca. 5 and 20% for the lipophilic
      toxins and there was no statistical difference between control and irradiated
      samples for azaspiracids in tissue. Irradiation of shellfish tissues contaminated
      with domoic acid led to a more continuous decrease in the amount of the toxin
      with increasing dose. The effect of irradiation on the viability of microbial
      activity in shellfish tissues was assessed by using total viable counting
      techniques. Microbial activity depended on the type of shellfish and on the
      pretreatment of the shellfish tissues (with or without heat treatment). As far as
      we are aware this is the first investigation of the effectiveness of irradiation
      as a technique for stabilising tissue reference materials for determination of
      phycotoxins. Our results suggest that this technique is not effective for
      materials containing domoic acid. It does, however, merit further investigation
      as a stabilisation procedure for preparation of shellfish tissue materials for
      some lipophilic toxins, in particular azaspiracids. Chemical structures of the
      toxins investigated in the study.

PMID- 17205265
TI  - New method for the photo-chemiluminometric determination of benzoylurea
      insecticides based on acetonitrile chemiluminescence.
AB  - The viability of tandem photochemical reaction-chemiluminescence detection has
      been studied for the determination of five benzoylurea insecticides, namely,
      diflubenzuron, triflumuron, hexaflumuron, lufenuron and flufenoxuron. The 'on
      line' photochemical reaction of benzoylurea pesticides provides an enhanced
      chemiluminescence response of the pesticides during their oxidation by potassium
      hexacyanoferrate(III) and sodium hydroxide, whose signal increases with the
      percentage of acetonitrile in the reaction medium. The determination was
      performed using a photoreactor consisting of a PFA (perfluoroalkoxy) tube reactor
      coil (5 mx1.6-mm O.D. and 0.8-mm I.D.) and an 8-W xenon lamp. As the yield of the
      photoderivatization process and the chemiluminescent signals depend on the
      percentage of acetonitrile, the chromatographic column (a Gemini C18, Phenomenex
      150 mmx4.6 mm, 5-microm particle size) was chosen with the aim of using high
      percentages of this organic solvent in the mobile phase. Previous studies showed
      that the rate of the chemiluminescent reaction was very fast. Therefore, a
      modification was carried out in the detector in order to mix the analytes and
      reactants as near as possible to the measure cell. The optimised method was
      validated with respect to linearity, precision, limits of detection and
      quantification accuracy. Under the optimised conditions, linear working range
      extends three orders of magnitude with the relative standard deviation of intra
      day precision below 10% and detection limits between 0.012 and 0.18 microg mL-1,
      according to the compound. The proposed method has been successfully applied to
      the determination of benzoylureas in cucumber with good results.

PMID- 17205266
TI  - A chemical uncertainty principle challenge.

PMID- 17205267
TI  - Surface plasmon resonance biosensor based on Hg/Ag-Au film.
AB  - Mercury or silver was electrodeposited on an Au surface to form an Hg-Au or Ag-Au
      film. Wavelength-modulation SPR biosensors based on this Hg/Ag-Au film were then
      used to determine human IgG and rabbit IgG. When direct immunoreactions were
      performed on the Au sensing surface, the range of concentrations of human IgG and
      rabbit IgG that could be determined were 2.00-40.00 microg/ml and 2.50-40.00
      microg/ml, respectively. When Hg was electrodeposited onto the Au film for 1200
      s, the range of concentrations of human IgG and rabbit IgG that could be
      determined were 0.50-40.00 microg/ml and 0.63-40.00 microg/ml, respectively. When
      Ag was electrodeposited onto the Au film for 1500 s, the range of concentrations
      of human IgG and rabbit IgG that could be determined were 0.25-20.00 and 0.42
      20.00 microg/ml, respectively. The biosensor based on Ag-Au film was therefore
      found to be the most sensitive of the three types of biosensor tested, giving
      limits of determination that were up to eight times lower than those obtained
      with a biosensor based on Au film alone.

PMID- 17205268
TI  - Novel methodology for the study of mercury methylation and reduction in sediments
      and water using 197Hg radiotracer.
AB  - Mercury tracers are powerful tools that can be used to study mercury
      transformations in environmental systems, particularly mercury methylation,
      demethylation and reduction in sediments and water. However, mercury
      transformation studies using tracers can be subject to error, especially when
      used to assess methylation potential. The organic mercury extracted can be as low
      as 0.01% of the endogenous labeled mercury, and artefacts and contamination
      present during methylmercury (MeHg) extraction processes can cause interference.
      Solvent extraction methods based on the use of either KBr/H2SO4 or HCl were
      evaluated in freshwater sediments using 197Hg radiotracer. Values obtained for
      the 197Hg tracer in the organic phase were up to 25-fold higher when HCl was
      used, which is due to the coextraction of 197Hg2+ into the organic phase during
      MeHg extraction. Evaluations of the production of MeHg gave similar results with
      both MeHg extraction procedures, but due to the higher Hg2+ contamination of the
      controls, the uncertainty in the determination was higher when HCl was used. The
      Hg2+ contamination of controls in the HCl extraction method showed a nonlinear
      correlation with the humic acid content of sediment pore water. Therefore, use of
      the KBr/H2SO4 method is recommended, since it is free from these interferences.
      197Hg radiotracer (T1/2=2.673 d) has a production rate that is about 50 times
      higher than that of 203Hg (T1/2=46.595 d), the most frequently used mercury
      radiotracer. Hence it is possible to obtain a similar level of performance to
      203Hg when it is used it in short-term experiments and produced by the
      irradiation of 196Hg with thermal neutrons, using mercury targets with the
      natural isotopic composition. However, if the 0.15% natural abundance of the
      196Hg isotope is increased, the specific activity of the 197Hg tracer can be
      significantly improved. In the present work, 197Hg tracer was produced from
      mercury 51.58% enriched in the 196Hg isotope, and a 340-fold increase in specific
      activity with respect to natural mercury targets was obtained. When this high
      specific activity tracer is employed, mercury methylation and reduction
      experiments with minimum mercury additions are feasible. Tracer recovery in
      methylation experiments (associated with Me197Hg production from 197Hg2+ spike,
      but also with Hg2+ contamination and Me197Hg artefacts) with marine sediments was
      about 0.005% g-1 WS (WS: wet sediment) after 20 h incubation with mercury
      additions of 0.05 ng g-1 WS, which is far below natural mercury levels. In this
      case, the amount of Hg2+ reduced to Hg0 (expressed as the percent 197Hg0
      recovered with respect to the 197Hg2+ added) varied from 0.13 to 1.6% g-1 WS.
      Me197Hg production from 197Hg2+ spike after 20 h of incubation of freshwater
      sediment ranged from 0.02 to 0.13% g-1 WS with mercury additions of 2.5 ng g-1
      WS, which is also far below natural levels. 197Hg0 recoveries were low, 0.0058+/
      0.0013% g-1 WS, but showed good reproducibility in five replicates. Me197Hg
      production from 197Hg2+ spiked in freshwater samples ranged from 0.1 to 0.3% over
      a period of three days with mercury additions of 10 ng L-1. A detection limit of
      0.05% for Me197Hg production from 197Hg2+ spike was obtained in seawater in a 25
      h incubation experiment with mercury additions of 12 ng L-1.

PMID- 17205269
TI  - Use of NIRS technology with a remote reflectance fibre-optic probe for predicting
      mineral composition (Ca, K, P, Fe, Mn, Na, Zn), protein and moisture in alfalfa.
AB  - In the present work we study the use of near-infrared spectroscopy (NIRS)
      technology together with a remote reflectance fibre-optic probe for the analysis
      of major (Ca, K, P) and minor (Fe, Mn, Na, Zn) elements, protein and moisture in
      alfalfa. The method allows immediate analysis of the alfalfa without prior sample
      treatment or destruction through direct application of the fibre-optic probe on
      ground samples in the case of the mineral composition and on-ground and compacted
      (baled) samples in the case of protein and humidity. The regression method
      employed was modified partial least-squares (MPLS). The calibration results
      obtained using samples of alfalfa allowed the determination of Ca, K, P, Fe, Mn,
      Na and Zn, with a standard error of prediction (SEP(C)) and a correlation
      coefficient (RSQ) expressed in mg/kg of alfalfa of 1.37x10(3) and 0.878 for Ca,
      1.10x10(3) and 0.899 for K, 227 and 0.909 for P, 103 and 0.948 for Fe, 5.1 and
      0.843 for Mn, 86.2 and 0.979 for Na, and of 1.9 and 0.853 for Zn, respectively.
      The SEP(C) and RSQ values (in %) for protein and moisture in ground samples were
      0.548 and 0.871 and 0.150 and 0.981, respectively; while in the compacted samples
      they were 0.564 and 0.826 and 0.262 and 0.935, respectively. The prediction
      capacity of the model and the robustness of the method were checked in the
      external validation in alfalfa samples of unknown composition, and the results
      confirmed the suitability of the method.

PMID- 17205270
TI  - Occurrence patterns of pharmaceuticals in water and wastewater environments.
AB  - The occurrence of pharmaceuticals and their metabolites and transformation
      products in the environment is becoming a matter of concern, because these
      compounds, which may have adverse effects on living organisms, are extensively
      and increasingly used in human and veterinary medicine and are released
      continuously into the environment. A variety of pharmaceuticals have been
      detected in many environmental samples worldwide. Their occurrence has been
      reported in sewage-treatment-plant effluents, surface water, seawater,
      groundwater, soil, sediment and fish. This paper provides an overview of recent
      scientific research on the sources, occurrence, and fate of pharmaceuticals in
      water and wastewater.

PMID- 17205271
TI  - Effect of silica nanoparticles with different sizes on the catalytic activity of
      glucose oxidase.
AB  - In this work we present a strategy for the covalent immobilization of periodate
      oxidized glucose oxidase (IO(4)(-) - GOx) to aminated silica nanoparticles
      (ASNPs) modified on gold electrodes. Silica nanoparticles greatly enhanced the
      catalytic ability of GOx toward the oxidation of glucose and improved the
      electron transfer between the GOx and the electrode surface. ASNPs of varying
      size--that is 100, 80, 60, and 30 nm--were prepared, and they were used to
      fabricate biosensors. Electrochemical impedance spectroscopy (EIS) of
      ferrocyanide followed the assembly process and verified the successful
      immobilization of IO(4)(-) - GOx on ASNPs modified on gold electrodes. From the
      analysis of catalytic signals of biosensors using different sizes of ASNPs under
      the same conditions, the surface concentration of electrically wired enzyme
      (Gamma (ET)) was estimated and was found to increase with decreasing ASNPs size.
      Therefore, the sensitivity of biosensors using smaller ASNPs was higher than that
      using larger particles. Specifically, we utilized the ASNPs with optimal size (30
      nm) to fabricate the glucose biosensor. The resulting electrodes showed a wide
      linear response to glucose at least to 6 mM and reached 95% of the steady-state
      current in less than 4 s with a sensitivity of 5.02 microA mM(-1) cm(-2) and a
      detection limit of 0.01 mM. The biosensor also showed excellent stability and
      good reproducibility.

PMID- 17205272
TI  - Reinventing yourself: marketing the experienced chemist in today's job market.

PMID- 17205273
TI  - Determination of epoxides by high-performance liquid chromatography following
      derivatization with N,N-diethyldithiocarbamate.
AB  - A reversed-phase, high-performance liquid chromatography (RP-HPLC) method that
      allows quantitation of low levels of epoxides has been described. The method
      involved derivatization of epoxides using 100- to 1,000-fold excess N,N
      diethyldithiocarbamate (DTC) at 60 degrees C for 20 min at neutral pH. The
      unreacted DTC was then decomposed to CS(2) and diethyl amine by acidification of
      the reaction mixture to pH 2 using orthophosphoric acid. The first two steps
      could be performed in the same reaction vessel by sequential addition of
      reagents. In the final step, an aliquot (20 microL) of the derivatized sample was
      analyzed for the presence of stable esters of DTC by RP-HPLC using a Supelcosil
      LC-18-S (150 x 4.6-mm) column and a mobile phase consisting of 40% (v/v)
      acetonitrile in water at a flow of 1 mL min(-1). Using UV detection at 278 nm,
      the epoxides gave linear responses in the concentration range of 0.25 to 50
      microM. The method is robust, and as low as 5 pmol of the analyte could be
      successfully detected and quantified with recoveries of > or =94%. Following a
      minimal pretreatment such as ultrafiltration (molecular weight cutoff 5,000 Da),
      the method is suitable for analysis of epoxides in complex physiological fluids
      (e.g., fetal bovine serum). The method has been rigorously evaluated and adapted
      in our laboratory for routine analysis and determination of stability of epoxides
      of 1,3-butadiene and other alkenes added to cell cultures.

PMID- 17205274
TI  - The impact of a cancer diagnosis on the health behaviors of cancer survivors and
      their family and friends.
AB  - GOALS: The aim of this study was to examine the effect of a cancer diagnosis on
      the health behaviors of cancer survivors and their family and friends, and to
      determine whether a cancer diagnosis could be a teachable moment for
      intervention. MATERIALS AND METHODS: This was a cross-sectional study of the
      health behaviors of individuals taking part in a cancer fundraising event. The
      questionnaire was completed by 657 participants. MAIN RESULTS: Participants were
      81.4% women, had a mean age of 46 years, and comprised of 17.2% cancer survivors.
      For cancer survivors, 31.3% reported an increase in physical activity, 50% of
      smokers quit, and 59 to 72% reported dietary improvements within 1 month of
      diagnosis. Significant differences in behavior change were found by age, but not
      by gender or education. For individuals without cancer, 24.3% reported improved
      physical activity and the majority reported some dietary changes. A greater
      proportion of family and friends who perceived they were at greater risk of
      developing cancer increased physical activity and sun-smart behavior but did not
      improve dietary habits. CONCLUSIONS: The results indicate that the cancer
      survivors made significantly more positive health behavior changes compared to
      the non-cancer group. For this sample, a personal diagnosis of cancer, or a
      diagnosis in a family member or friend, may have acted as a 'cue to action' to
      improve lifestyle health behaviors. This field of research is still at an early
      stage, and further studies are needed to confirm if this situation could be
      useful as a 'teachable moment' for intervention purposes.

PMID- 17205275
TI  - A population-based study on the specific locations of cancer deaths in Taiwan,
      1997-2003.
AB  - INTRODUCTION: In traditional Taiwanese culture, home death is generally regarded
      as implying a good death, as it is believed that the spirit will not be left to
      wander. The purpose of this study was to determine the place of death and
      identify the predictors of home deaths for all cancer patients in Taiwan.
      MATERIALS AND METHODS: We undertook a population-based study using death
      registration data on all cancer deaths which occurred in Taiwan between 1997 and
      2003. In total, 173,187 eligible cancer deaths occurring during the period were
      examined. RESULTS: Results revealed that around 60% of all cancer deaths in
      Taiwan between 1997 and 2003 occurred at home. Female cancer patients and those
      aged between 55 and 64 years, who were either married or widowed, living in less
      urbanized areas of Taiwan, and areas with a low density of hospital beds, were
      found to be more likely to have died at home. Results from the logistic
      regression revealed that predictors for a home death included being female, aged
      more than 55 years, having been married, being employed, having respiratory
      cancer, living in central Taiwan, and living in less-urbanized areas. DISCUSSION:
      There is increased awareness on a global scale of the desire among terminally ill
      patients to be able to die at home, and indeed, we are seeing greater efforts
      towards promoting home deaths; however, greater palliative home care services
      will be necessary if home deaths are to become a feasible option in Taiwan.

PMID- 17205276
TI  - Factors associated with poor general health after stem-cell transplantation.
AB  - AIMS: To describe functional status (FS), general health (GH) and symptom
      distress (SD) from admission to 1 year post-SCT and to identify medical,
      demographic, and/or patient-reported outcome variables associated with patient
      perceived GH. MATERIAL AND METHODS: Forty-one patients (27 women) with a median
      age of 44 (18-65) years answered three questionnaires (SIP, SWED-QUAL, and SFID
      SCT) from admission to 1 year post-SCT. RESULTS: At discharge, 59% of the
      patients reported poor FS and GH, and 24% reported > 10 simultaneous symptoms.
      After 1 year post-SCT, 22% still reported poor FS, 32% poor GH, and 12% > 10
      simultaneous symptoms. Compared with admission, significantly larger proportions
      of the patients reported poor GH at discharge (20 vs 59%, p = .001), poor FS at 6
      months (24 vs 59%, p = .004), and poor GH [The number of symptoms was found to be
      significantly associated with poor GH at discharge (OR 1.330, p = .009) and at 1
      year post-SCT (OR 2.000, p = .010)]. Patients reporting "poor GH" at discharge
      and at 1 year post-SCT reported a median of 7 and 10 symptoms, respectively.
      Patients with "good GH" reported a median of three symptoms both at T1 and T4.
      "Tiredness", "anxiety", "mouth dryness", "loss of appetite", and "diarrhoea" were
      reported by a larger proportion of the patients reporting "poor GH". CONCLUSIONS:
      The results confirm that some patients who have undergone a SCT have a negatively
      affected life situation. The study indicates that actively asking for symptoms
      and applying the best treatment for symptom alleviation are among the most
      important measures that SCT teams can take to help the patients perceive better
      general health and an improved life situation.

PMID- 17205277
TI  - Demographic, medical, and psychosocial correlates to CAM use among survivors of
      colorectal cancer.
AB  - GOALS OF WORK: Complementary and alternative medicines (CAM) use among cancer
      patients is becoming more prevalent; however, our understanding of factors
      contributing to patients' decisions to participate in CAM is limited. This study
      examined correlates of CAM use among colorectal cancer (CRC) survivors, an
      understudied population that experiences many physical and psychological
      difficulties. MATERIALS AND METHODS: The sample was 191, predominantly white, CRC
      survivors (mean age = 59.9 +/- 12.6) who were members of a colon disease registry
      at a NYC metropolitan hospital. Participants completed assessments of
      sociodemographic characteristics, psychosocial factors [e.g., psychological
      functioning, cancer specific distress, social support (SS), quality of life
      (QOL)], and past CAM use (e.g., chiropractic care, acupuncture, relaxation,
      hypnosis, and homeopathy). MAIN RESULTS: Seventy-five percent of participants
      reported using at least one type of CAM; most frequently reported was home
      remedies (37%). Younger (p < 0.01) or female patients (p < 0.01) were more likely
      to participate in CAM than their older male counterparts. Among psychosocial
      factors, poorer perceived SS (p = 0.00), more intrusive thoughts (p < 0.05), and
      poorer overall perceived QOL (p < 0.05) were associated to CAM use. In a linear
      regression model (including age, gender, SS, intrusive thoughts, and perceived
      QOL), only age remained a significant predictor of CAM use. CONCLUSION: These
      findings demonstrate that CAM use is prevalent among CRC survivors and should be
      assessed routinely by providers. CAMs may serve as a relevant adjunct to
      treatment among CRC patients as well as an indication of need for additional SS,
      especially among younger patients.

PMID- 17205278
TI  - Impact of family structure on long-term survivors of osteosarcoma.
AB  - GOALS OF WORK: Long-term outcomes of osteosarcoma have dramatically improved with
      the use of modern combination therapies. Such aggressive treatments, however,
      entail chronic complications. In the present study, we assessed the functional,
      psychological, and familial status of long-term survivors of osteosarcoma treated
      at our institution. MATERIALS AND METHODS: Fifteen long-term survivors of
      osteosarcoma were evaluated for functional and psychological sequelae. Functional
      assessment was based on a method described by Enneking et al. Psychological
      assessment was based on General Health Questionnaire 28, Inventory Scale for
      Traumatic Neurosis, and Family System Test. MAIN RESULTS: Ten patients showed
      mild functional impairments; only five patients were handicapped more seriously.
      Depressive symptoms were diagnosed in four patients. A total of six patients
      revealed unbalanced family structures, including three of the four patients with
      depressive symptoms, all four patients with symptoms of posttraumatic stress
      disorder, and five of seven patients who showed poor emotional acceptance.
      CONCLUSIONS: Osteosarcoma survivors will generally recover good functional
      performance. Only a minority of them remain seriously impaired. One third of the
      patients present depressive symptoms and posttraumatic stress disorder. Poor
      coping is closely associated with unbalanced family structures. Therefore, the
      psychological and familial situation of patients with newly diagnosed
      osteosarcoma should be carefully assessed.

PMID- 17205279
TI  - Determining mucosal barrier injury to the oesophagus using CT scan.
AB  - INTRODUCTION: Oral mucositis is recognised as one of the most debilitating
      complications of high-dose cytostatic chemotherapy used to prepare for
      haematopoietic stem cell transplantation (HSCT), but very little is known about
      oesophageal mucositis, as endoscopy is not routinely performed. MATERIALS AND
      METHODS: We incorporate the computed tomography (CT) scan in the diagnostic
      workup of fever during neutropenia to detect evidence of pulmonary complications.
      This allowed us to evaluate whether mucosal barrier injury to the oesophagus can
      be determined. We selected 46 patients without oesophageal cancer or immune
      suppression (controls), who had a normal oesophagus, and measured the mucosal
      thickness at the upper part (UP), middle part (MP) and lower part (LP) of the
      oesophagus. Next, we selected 30 patients having a CT scan done for diagnostic
      purposes within 14 days after HSCT and measured mucosal thickness at the same
      levels. We also scored oral mucositis and gut toxicity. RESULTS: The mucosal
      thickness of the UP, MP and LP, respectively, for the controls (mean +/- SD) was
      4.1 mm (+/-1.1), 4.2 mm (+/-1.2) and 4.8 mm (+/-1.3), and the corresponding
      values for the subjects were 5.9 mm (+/-2.2), 5.9 mm (+/-2.0) and 7.7 mm (+/
      3.0). Analysis of variance showed statistically significant differences between
      subjects and controls at all oesophageal levels. All patients suffered from
      severe oral mucositis at the time. CONCLUSION: Hence, mucosal barrier injury to
      the oesophagus can be objectively measured using CT scan.

PMID- 17205280
TI  - Change in quality of life in Chinese women with breast cancer: changes in
      psychological distress as a predictor.
AB  - INTRODUCTION: The effect of fluctuating psychological distress on quality of life
      (QoL) scores is not well delineated. We examined how changes in psychological
      distress affected change in QoL over time in 259 Chinese women recovering from
      breast cancer (BC). PATIENTS AND METHODS: Women were interviewed during their
      first postoperative outpatient visit for chemotherapy (Baseline), at 3 months
      (FU1), and at 6 months after Baseline (FU2). Respondents completed the Chinese
      version of the FACT-G version-3 scale [FACT-G (Ch)]. Psychological distress was
      assessed using three categorical measures of depression, mood, and boredom.
      Linear mixed effects (LME) models examined whether changes in psychological
      distress predicted subsequent changes in QoL. RESULTS: Respondents' mood improved
      significantly over time from baseline to FU2 (Baseline/FU2: standardized beta = 
      0.266, p < 0.005; FU1/FU2: standardized beta = -0.243, p < 0.005). Changes in
      depression scores consistently predicted subsequent changes in overall
      (standardized beta = 4.96; 95% CI, 3.749, 6.171, p < 0.001), physical
      (standardized beta = 1.752; 95% CI, 1.209, 2.294, p < 0.001), and functional
      (standardized beta = 0.872; 95% CI, 0.308, 1.436, p < 0.001) QoL scores.
      CONCLUSIONS: The magnitude of change in psychological distress significantly
      impacted physical and functional, but not social QoL in Chinese BC patients.
      These data highlight the need to address psychological and physical distress as
      part of the drive to improve physical and functional QoL for women with BC.

PMID- 17205282
TI  - A survey of National Cancer Institute-designated comprehensive cancer centers'
      oral health supportive care practices and resources in the USA.
AB  - BACKGROUND: The oral complications and morbidity resulting from overall cancer
      therapy utilizing radiation, chemotherapy, and/or stem cell transplantation can
      have significant impact on a patient's health, quality of life, cost of care, and
      cancer management. There has been minimal health services research focusing on
      the status of medically necessary, oral supportive services at US cancer centers.
      METHODS: A pre-tested, survey questionnaire was distributed to the directors of
      National Cancer Institute (NCI)-designated comprehensive cancer centers to assess
      each institution's resource availability and clinical practices, as it relates to
      the prevention and management of oral complications during cancer treatment.
      RESULTS: Sixteen of the 39 comprehensive cancer centers responded to the survey.
      Of the respondents, 56% of the centers did not have a dental department. The
      sites of delivery of oral supportive care services range from the provision of in
      house dental care to community-based, private practice sites. No standard
      protocols were in place for either oral preventive care or for supportive
      services for oral complications during or after cancer therapy. Fifty percent of
      the responding comprehensive cancer centers reported orally focused research
      and/or clinical trial activities. CONCLUSIONS: Comprehensive cancer care must
      include an oral care component, particularly for those cancer patients who are at
      high risk for oral complications. This requires a functional team of oral care
      providers collaborating closely within the oncology team. Considering the number
      of cancer patients receiving aggressive oncologic treatment that may result in
      oral toxicity, the impact of oral conditions on a compromised host, and the
      potential lack of appropriate resources and healthcare personnel to manage these
      complications, future research efforts are needed to identify the strengths and
      weaknesses of present oral supportive care delivery systems at both NCI
      designated cancer centers and community-based oncology practices.

PMID- 17205281
TI  - A meta-analysis comparing the efficacy of four 5-HT3-receptor antagonists for
      acute chemotherapy-induced emesis.
AB  - GOALS OF WORK: Comparing antiemetic efficacy of different 5-HT(3)-receptor
      antagonists (5-HT(3)RAs) is difficult due to inter-study variability. Therefore,
      a meta-analysis was performed to comparatively evaluate dolasetron, granisetron,
      ondansetron and tropisetron for acute chemotherapy-induced nausea and vomiting
      (CINV). PATIENTS AND METHODS: Comparisons between 5-HT(3)RAs were based on 44
      randomized studies (including 12,343 patients) identified by MEDLINE, CANCERLIT
      or EMBASE searches and subcategorized by chemotherapy type (cisplatin- or non
      cisplatin-based). MAIN RESULTS: When all studies were combined, granisetron was
      equivalent to ondansetron (n = 27), and showed an advantage vs tropisetron (p =
      0.018; n = 12). Ondansetron vs tropisetron (n = 11) and ondansetron vs dolasetron
      (n = 3) revealed equivalence in each comparison. An advantage for 3 mg
      granisetron vs 8 mg ondansetron was found in non-cisplatin-based studies (p =
      0.015; n = 6). Overall equivalence was seen between ondansetron, 24 or 32 mg, and
      granisetron, 2 or 3 mg, for all studies (n = 13). There was a possible advantage
      for higher (24 or 32 mg) vs lower (8 mg) ondansetron dose regimens with cisplatin
      based trials (n = 6). No differences were seen between 3 and 1 mg granisetron
      doses (n = 6). CONCLUSIONS: Efficacy of 5-HT(3)RAs for preventing CINV following
      cisplatin- and non-cisplatin-based chemotherapy is comparable, with the exception
      of granisetron vs tropisetron. Some differences were noted in dosing subanalyses.

PMID- 17205284
TI  - Pulmonary nodular opacities in children with hereditary hemorrhagic
      telangiectasia.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare inherited
      disorder of vascular endothelium that can result in the formation of pulmonary
      arteriovenous malformations (pAVMs). We observed that small pulmonary nodules,
      possibly representing early vascular malformations, are more common in these
      children than in the general population. OBJECTIVE: To describe and characterize
      the small pulmonary nodules seen on chest CT examination in the lungs of children
      with HHT. MATERIALS AND METHODS: We followed 19 children who had undergone chest
      CT as part of their initial diagnostic evaluation in the HHT clinic of a
      pediatric hospital. Chest CT scans were reviewed independently by two
      radiologists blinded to clinical data. Pulmonary nodules were analyzed according
      to lobar distribution, anatomic position in the lung (outer, mid, inner third),
      shape (round, linear, V- or Y-shaped, ill-defined), presence of overt AVMs, and
      nodule size (<or= or >5 mm). We also reviewed a control group of chest CT scans
      performed on 25 age-matched children. RESULTS: A total of 35 pulmonary nodules
      were identified on the CT scans in 15 of the 19 children. Multiple nodules were
      seen in eight children (42%), solitary nodules were seen in seven children (37%)
      and no nodules were seen in the remaining four children (21%). The nodules were
      found to be nonspecific with regard to multiple factors other than their anatomic
      position within the lung. The chest CT scans of 2 of the 25 age-matched controls
      revealed a total of only four nodules, a significantly lower total (P = 0.0001
      vs. children with HHT). CONCLUSION: Nonspecific nodules are commonly seen in
      children with HHT.

PMID- 17205283
TI  - Malaria-induced renal damage: facts and myths.
AB  - Malaria infections repeatedly have been reported to induce nephrotic syndrome and
      acute renal failure. Questions have been raised whether the association of a
      nephrotic syndrome with quartan malaria was only coincidental, and whether the
      acute renal failure was a specific or unspecific consequence of Plasmodium
      falciparum infection. This review attempts to answer questions about "chronic
      quartan malaria nephropathy" and "acute falciparum malaria nephropathy". The
      literature review was performed on all publications on kidney involvement in
      human and experimental malarial infections accessible in PubMed or available at
      the library of the London School of Hygiene and Tropical Medicine. The
      association of a nephrotic syndrome with quartan malaria was mostly described
      before 1975 in children and rarely in adult patients living in areas endemic for
      Plasmodium malariae. The pooled data on malaria-induced acute renal failure
      included children and adults acquiring falciparum malaria in endemic areas either
      as natives or as travellers from non-tropical countries. Non-immunes (not living
      in endemic areas) had a higher risk of developing acute renal failure than semi
      immunes (living in endemic areas). Children with cerebral malaria had a higher
      rate and more severe course of acute renal failure than children with mild
      malaria. Today, there is no evidence of a dominant role of steroid-resistant and
      chronic "malarial glomerulopathies" in children with a nephrotic syndrome in
      Africa. Acute renal failure was a frequent and serious complication of falciparum
      malaria in non-immune adults. However, recently it has been reported more often
      in semi-immune African children with associated morbidity and mortality.

PMID- 17205285
TI  - Secondary myelodysplastic syndrome after hydroxychloroquine therapy.
AB  - Primary myelodysplastic syndromes (MDS) occur in the absence of exposure to
      ionizing radiation, chemotherapeutic agents or myelotoxic drugs, whereas
      secondary MDS occurs in the presence of such exposure. We encountered 4 patients
      among 217 patients on hydroxychloroquine for rheumatological conditions in 2005
      diagnosed with MDS. Two patients were male and two were female; the median age
      was 69.75 years, (range 65-76). The dose of hydroxychloroquine for all patients
      was 400 mg daily with median treatment duration of 10.5 years and a range of 6
      16. All patients had bone marrow biopsy confirmation of the diagnosis of MDS. The
      incidence of MDS in a group older than 70 years ranges from 15 to 50/100,000
      persons per year. The diagnosis of 4 cases of MDS among 217 patients in 1 year is
      approximately 123-137-fold higher than the risk of MDS in the general population
      aged more than 70 years (P < 0.001) and suggests that long-term treatment with
      hydroxychloroquine is associated with an increased risk of developing secondary
      MDS.

PMID- 17205286
TI  - Leukocyte numbers correlate with plasma levels of granulocyte-macrophage colony
      stimulating factor in sickle cell disease.
AB  - Despite a clear role for leukocytes in modulating the pathophysiology of sickle
      cell disease (SCD), the mechanism by which leukocyte numbers are increased in
      this disorder remains unclear. Hypothesizing that the chronic inflammatory state,
      elicited by adhesive interactions involving various cell types, might underlie
      leukocytosis, we measured plasma levels of proinflammatory or myeloid cytokines
      that play a role in leukocytosis and examined their correlations with leukocyte
      numbers in patients with SCD. Our studies found that, although plasma levels of
      granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3, and
      macrophage colony-stimulating factor are elevated in steady-state patients with
      SCD, only plasma GM-CSF levels are positively correlated with the numbers of
      total leukocytes, neutrophils, monocytes, and eosinophils, regardless of whether
      they received hydroxyurea. GM-CSF levels were significantly decreased in patients
      on hydroxyurea therapy. These data suggest a role of GM-CSF in leukocytosis of
      SCD. In contrast, plasma levels of granulocyte colony-stimulating factor, a major
      cytokine that induces leukocytosis due to bacterial infection, were lower than
      those of control subjects. These results indicate that elevated GM-CSF levels may
      contribute, at least in part, to high leukocyte numbers in SCD. As plasma GM-CSF
      levels were decreased in patients on hydroxyurea therapy, hydroxyurea may
      decrease leukocyte numbers by reducing circulating GM-CSF levels.

PMID- 17205287
TI  - Towards a new age in the treatment of multiple myeloma.
AB  - Multiple myeloma (MM) is an incurable disease characterized by the proliferation
      of end-stage B lymphocytes (plasma cells, PCs). As a consequence of myeloma
      growth in the bone marrow, a number of signaling pathways are activated that
      trigger malignant PC proliferation, escape from apoptosis, migration, and
      invasion. Thanks to new insights into the molecular pathogenesis of MM, novel
      approaches aimed at targeting these abnormally activated cascades have recently
      been developed and others are under study. These strategies include the
      inhibition of membrane receptor tyrosine kinases, inhibition of the
      proteasome/aggresome machinery, inhibition of histone deacetylases, inhibition of
      farnesyltransferases, targeting of molecular chaperones, and others. We will
      herein review and discuss these novel biological approaches with particular
      emphasis on those based on biochemical pathways which drive cell signaling. By
      providing the rationale for innovative therapeutic strategies, the above
      mechanisms represent targets for new compounds being tested in the management of
      this disease.

PMID- 17205288
TI  - Overexpressed platelet integrin alphaIIbbeta3 in a Fechtner syndrome patient
      uneventfully undergoing adenotomy.

PMID- 17205289
TI  - Scrotal ulcerations during all-transretinoic acid therapy for acute promyelocytic
      leukemia.

PMID- 17205290
TI  - Social learning and innovation are positively correlated in pigeons (Columba
      livia).
AB  - When animals show both frequent innovation and fast social learning, new
      behaviours can spread more rapidly through populations and potentially increase
      rates of natural selection and speciation, as proposed by A.C. Wilson in his
      behavioural drive hypothesis. Comparative work on primates suggests that more
      innovative species also show more social learning. In this study, we look at
      intra-specific variation in innovation and social learning in captive wild-caught
      pigeons. Performances on an innovative problem-solving task and a social learning
      task are positively correlated in 42 individuals. The correlation remains
      significant when the effects of neophobia on the two abilities are removed.
      Neither sex nor dominance rank are associated with performance on the two tasks.
      Free-flying flocks of urban pigeons are able to solve the innovative food-finding
      problem used on captive birds, demonstrating it is within the range of their
      natural capacities. Taken together with the comparative literature, the positive
      correlation between innovation and social learning suggests that the two
      abilities are not traded-off.

PMID- 17205291
TI  - The protective effect of dexpanthenol on testicular atrophy at 60th day following
      experimental testicular torsion.
AB  - Despite the prompt diagnosis and treatment of testicular torsion (TT), there are
      problems with fertility and atrophy after testicular salvage. Dexpanthenol (Dxp)
      is the biologically active alcohol of pantothenic acid (PA). Dxp is converted to
      PA in tissues. PA increases the content of reduced glutathione (GSH), Coenzyme A
      and ATP synthesis in cells. GSH and glutathione-dependent peroxidases (GPX) are
      the major defense systems against oxidative stress. GPX-4 is the major
      antioxidant in testicular tissue. However, the activity of GPX-4 appeared and
      increased only after puberty. We investigated the effect of Dxp on testicular
      atrophy after TT at the 60th day. Rats were separated randomly into four groups.
      Group C: control group, group Td: torsion + detorsion, group Sal: torsion +
      saline + detorsion, group Dxp: torsion + Dxp + detorsion. The left testis was
      rotated 720 degrees for 2 h. In group Sal, normal saline and in group Dxp,
      Dexpanthenol were injected intraperitonally, 30 min before detorsion. After 60
      days, the testicular weights and volumes were measured. Histopathology of the
      left testis was evaluated with mean seminiferous tubular diameter (MSTD) and mean
      testicular biopsy score (MTBS). The left (torsed) testicular weight and volume of
      groups Td and Sal were significantly lower compared to group Dxp. The MSTD and
      MTBS of group Td and Sal were significantly lower than group Dxp. Contralateral
      testicular weight and volume of groups Td, Sal and Dxp had no significant
      difference compared to the control group. Dxp significantly prevented testicular
      atrophy after 60 days of TT. Dxp has FDA approval, is safe, cost effective and
      readily available. Its relevance for clinical trials may especially be for the
      problem of testicular atrophy catastrophe, seen very frequently following
      testicular salvage.

PMID- 17205292
TI  - Immunonutritional effects during synbiotics therapy in pediatric patients with
      short bowel syndrome.
AB  - The aim of this study was to evaluate the effects of synbiotic therapy in
      patients with short bowel syndrome (SBS). Four pediatric patients with SBS, who
      were receiving synbiotics therapy including Bifidobacterium breve, Lactobacillus
      casei and galactooligosaccharides, were enrolled in this study. We evaluated
      changes in immunonutritional parameters before and after receiving synbiotics
      therapy. Four normal, healthy, age-matched children were enrolled as controls.
      Fecal samples from patients and controls were collected and analyzed for fecal
      bacterial flora and organic acid (OA) contents. Levels of short chain fatty acids
      (SCFA) such as butyrate, propionate, and acetate increased in one patient, and
      SCFA/total OA levels increased in three patients. Serum lymphocyte counts and
      concentrations of pre-albumin increased after beginning synbiotics therapy,
      reaching a statistically significant level at the ninth month compared to the pre
      treatment level. There was an increasing trend in height and weight gain velocity
      during the study compared with the pre-treatment period. The patients' fecal
      bacterial flora improved as a result of synbiotics therapy. Synbiotics therapy
      may be very effective at improving the intestinal flora and systemic
      immunonutritional status of patients with SBS.

PMID- 17205293
TI  - Intestinal epithelial cell proliferation is dependent on the site of massive
      small bowel resection.
AB  - Early intestinal adaptation after massive small bowel resection (SBR) is driven
      by increased epithelial cell (EC) proliferation. There is a clear clinical
      difference in the post-operative course of patients after the loss of proximal
      (P) compared to distal (D) small bowel. This study examined the effects of the
      site of SBR on post-resectional intestinal adaptation, and investigated the
      potential mechanisms involved. C57BL/6J mice (n = 7/group) underwent: (1) 60% P
      SBR, (2) 60% D-SBR, (3) 60% mid (M)-SBR and (4) SHAM-operation
      (transection/reanastomosis). Mice were sacrificed at 7 days after surgery and ECs
      and adjacent mucosal lymphocytes (IELs) isolated. Adaptation was assessed in both
      jejunum and ileum by quantification of villus height, crypt depth, villus cell
      size, crypt cell size (microns), goblet cell number, and EC proliferation (%BrdU
      incorporation). Proliferation signalling pathways including keratinocyte growth
      factor (KGF)/KGFR(1), IL-7/IL-7R, and epidermal growth factor receptor (EGFR)
      were measured by RT-PCR. Expression of IL-7 was further analysed by
      immunofluorescence. Data were analyzed using ANOVA. All three SBR models led to
      significant increases in villus height, crypt depth, goblet cell numbers and EC
      proliferation rate when compared to respective SHAM groups. The strongest
      morphometric changes were found for jejunal segments after M-SBR and for ileal
      segments after P-SBR. Furthermore, morphometric analysis showed that at 1-week
      post-resection a tremendous increase in EC numbers occurred in jejunal villi
      (cell hyperplasia), whereas a significant increase in EC size predominated in
      ileal villi (cell hypertrophy). mRNA expression of KGF, KGFR(1), IL-7R, and EGFR
      showed a significant increase only after D-SBR, whereas IL-7 increased
      significantly after SBR in all investigated models, and this was confirmed by
      immunofluorescence studies. Early intestinal adaptation shows distinct
      differences depending on the site of SBR, and is predominately driven by cell
      hyperplasia in jejunal villi and cell hypertrophy in ileal villi. However, the
      exact mechanisms, which guide these signalling pathways are still unclear.

PMID- 17205294
TI  - Pleural macrophages are the dominant cell population in the thoracic cavity with
      an inflammatory cytokine profile similar to peritoneal macrophages.
AB  - Numerous human macrophage (mphi) subpopulations with different behavior have been
      identified in adults. It is well known that peritoneal mphi are activated by
      abdominal surgery and subsequently contribute to a systemic inflammatory response
      that leads to immune suppression, increased morbidity and mortality. Information
      on the role of pleural mphi in adults is scarce and information on their role in
      children is lacking. We investigated the behavior of pleural versus peritoneal
      mphi in children and adolescents. As a first step, we compared the cellular
      composition of the pleural and peritoneal surface in children and adolescents.
      Pleural and peritoneal lavages were performed in 21 patients undergoing non
      contaminated laparoscopic and thoracoscopic surgical procedures. We observed a
      significantly higher percentage of mphi in the pleural compared to the peritoneal
      cavity with less lymphocytes, a small amount of polymorphonuclear cells (PMNs)
      and other cells. To further study the mphi inflammatory response, we measured the
      spontaneous and LPS triggered cytokine release of isolated pleural versus
      peritoneal mphi (IL-1beta, IL-6, and IL-10). The pattern of cytokine release was
      similar in both, pleural and peritoneal mphi. Directly after lavage, they showed
      a strong activation, with no difference between stimulated and non-stimulated
      cells. After 24 h resting, mphi of both compartments reacted to LPS with a
      similar significant increase in the cytokine release. In conclusion, our results
      demonstrate that pleural mphi represent the dominant cell population in the
      pleural cavity of the young. They show a similar inflammatory response as
      peritoneal mphi and should be considered to play a major role in the local
      inflammatory response to thoracic surgery.

PMID- 17205295
TI  - A new rapid acetylcholinesterase staining kit for diagnosing Hirschsprung's
      disease.
AB  - Conventional acetylcholinesterase (AChE) histochemistry is both time consuming
      and complicated and requires the mixing of reagents that are toxic to the human
      body. We developed a rapid technique for performing AChE histochemistry, which
      has already been published, and now present a kit for performing AChE
      histochemistry that is a further improvement. Rectal suction biopsy specimens
      taken from 20 constipated patients and three full thickness biopsy specimens
      taken from 4 Hirschsprung's disease (HD) patients during pull-through surgery
      from aganglionic, transitional, and ganglionic bowel segments were tested using
      our rapid technique and the new kit. Each specimen was incubated for only 6 min.
      All ganglion cells stained clearly for AchE in just 6 min using both techniques.
      However, the kit was able to stain AchE positive nerve fibers more clearly and
      did not detect endogenous peroxidase-containing histiocytes, as did the earlier
      rapid technique. The kit could also detect AchE positive nerve fibers in the
      circular and longitudinal muscle layers, unlike the earlier rapid technique. The
      kit allows AChE histochemistry to be performed rapidly with complete accuracy,
      without any risk for toxicity. Moreover, the kit provides more focused
      information on AchE distribution in the bowel itself without any extraneous
      staining and can be used for diagnosing HD and allied disorders as well as
      establishing the exact level of innervation for pull-through resection.

PMID- 17205296
TI  - Adriamycin mouse model: a variable but reproducible model of tracheo-oesophageal
      malformations.
AB  - A spectrum of tracheo-oesophageal malformations is seen in humans: oesophageal
      atresia, tracheal agenesis and laryngotracheo-oesophageal clefts. They are
      thought to share a common but unknown aetiology. These birth defects are
      frequently associated with other VACTERL anomalies. The adriamycin rat model
      (ARM) has proved to be a valuable model of the VACTERL anomalies, illustrating
      the dysmorphogenesis of oesophageal atresia and tracheal agenesis. As
      organogenesis relies on temporaspatially co-ordinated signalling systems, the
      next step would be to study the molecular pathogenesis of tracheo-oesophageal
      malformations. However, the mouse is the foremost mammal studied by developmental
      biologists, offering an expanding wealth of knowledge and scientific research
      techniques with which to investigate these anomalies. A limited dose response
      analysis of the teratogenicity of adriamycin in the mouse has identified a dose
      and timing of injections that produced tracheo-oesophageal malformations and
      other VACTERL anomalies. A clear account of the types and variability of the
      tracheo-oesophageal malformations produced by this dose is essential in order to
      be able to plan and interpret any future investigations of early gestation
      fetuses. CBA/Ca mice were accurately time-mated (n = 10). Nine dams received
      intraperitoneal injections of adriamycin (6 mg/kg) and one control dam received
      saline injections, on days 7 and 8. Fetuses were harvested on day 18, near term.
      Tracheo-oesophageal malformations were examined by dissecting microscope and
      serial transverse sections. Results are reported in the standard teratological
      manner as mean percentage per litter (+/-SEM). The resorption rate of the
      adriamycin treated fetuses was 50.4%. There were 29 adriamycin treated fetuses
      for inspection. Tracheo-oesophageal malformations were found in 29.2% (+/-10.3),
      affecting five out of nine litters. Oesophageal atresia occurred in 15.6% (+/
      8.1), laryngotracheo-oesophageal cleft in 10.4% (+/-7) and tracheal agenesis in
      3.1% (+/-3.1). All of these malformations occurred with a tracheo-oesophageal
      fistula. Unlike the ARM, the AMM can produce fetuses with complete laryngotracheo
      oesophageal cleft as well as oesophageal atresia or tracheal agenesis. Their
      occurrence was found to be reproducible but variable. These are important
      considerations when planning and interpreting experiments using this model.

PMID- 17205297
TI  - A new approach to blue rubber bleb nevus syndrome: the role of capsule endoscopy
      and intra-operative enteroscopy.
AB  - Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular malformation disorder
      with cutaneous and visceral lesions frequently associated with serious, even
      fatal bleeding and anemia. The syndrome is considered to be autosomaly
      predominantly inherited. Intra-operative enteroscopy (IOE) is the best method of
      identification of all lesions (particularly the small ones, less than 3 mm) and
      treatment by endoscopic electro-coagulation or surgical excision. Capsule
      wireless endoscopy is optimal for screening before the IOE and for monitoring the
      effect of therapy (in patients with BRBNS). We report two cases of BRBNS. Anemia,
      gastrointestinal bleeding, gastrointestinal malformations and multifocal venous
      malformations of the skin were present in both of our cases. Gastrointestinal
      lesions were identified by gastroscopy, colonoscopy and capsule endoscopy. The
      multiple venous malformations were treated partly by endoscopic electro
      coagulation (lesions up to 4 mm in diameter) and by wedge resection. Both of our
      patients were 12-year-old girls at the time of operation. In the first patient 31
      venous malformations of the small bowel were coagulated, two were resected by the
      surgeon. In the second patient 20 lesions were coagulated endoscopically and
      another 31 nevi were resected during an 8 h procedure. The first girl is doing
      fine 4 years after the procedure, the second was allowed home 2 weeks after the
      procedure in excellent condition. IOE is a unique method of small bowel
      investigation and concurrently provides a solution for pathological findings.
      Capsule endoscopy is a feasible non-invasive screening procedure. We believe that
      a radical eliminatory approach by means of combined surgery and IOE is indicated
      for the BRBNS to prevent ongoing gastrointestinal bleeding.

PMID- 17205298
TI  - Spatial symmetries in vestibular projections to the uvula-nodulus.
AB  - The discharge of secondary vestibular neurons relays the activity of the
      vestibular endorgans, occasioned by movements in three-dimensional physical
      space. At a slightly higher level of analysis, the discharge of each secondary
      vestibular neuron participates in a multifiber projection or pathway from primary
      afferents via the secondary neurons to another neuronal population. The logical
      organization of this projection determines whether characteristics of physical
      space are retained or lost. The logical structure of physical space is standardly
      expressed in terms of the mathematics of group theory. The logical organization
      of a projection can be compared to that of physical space by evaluating its
      symmetry group. The direct projection from the semicircular canal nerves via the
      vestibular nuclei to neck motor neurons has a full three-dimensional symmetry
      group, allowing it to maintain a three-dimensional coordinate frame. However, a
      projection may embed only a subgroup of the symmetry group of physical space,
      which incompletely mirrors the properties of physical space. The major visual and
      vestibular projections in the rabbit via the inferior olive to the uvula-nodulus
      carry three degrees of freedom-rotations about one vertical and two horizontal
      axes-but do not have full three dimensional symmetry. Instead, the vestibulo
      olivo-nodular projection has symmetries corresponding to a product of two
      dimensional vestibular and one-dimensional optokinetic spaces. This combination
      of projection symmetries provides the foundation for distinguishing horizontal
      from vertical rotations within a three dimensional space. In this study, we
      evaluate the symmetry group given by the physiological organization of the
      vestibulo-olivo-nodular projection. Although it acts on the same sets of elements
      and mirrors the rotations that occur in physical space, the physiological
      transformation group is distinct from the spatial group. We identify symmetries
      as products of physiological and spatial transformations. The symmetry group
      shapes the information the projection conveys to the uvula-nodulus; this shaping
      may depend on a physiological choice of generators, in the same way that function
      depends on the physiological choice of coordinates. We discuss the implications
      of the symmetry group for uvula-nodulus function, evolution, and functions of the
      vestibular system in general.

PMID- 17205299
TI  - The channel-lining 6' amino acid in the second membrane-spanning region of
      ionotropic GABA receptors has more profound effects on 4'-ethynyl-4-n
      propylbicycloorthobenzoate binding than the 2' amino acid.
AB  - The noncompetitive antagonist of ionotropic gamma-aminobutyric acid (GABA)
      receptors 4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB) is a useful tool to
      probe the antagonist-binding site. In the present study, four mutants of the
      human GABA(A) receptor beta3 subunit were stably expressed in S2 cells and
      examined for their abilities to bind [(3)H]EBOB to identify the binding site of
      EBOB. The homo-oligomeric beta3 GABA receptor was used as a housefly GABA
      receptor model, as the beta3 subunit has a high sequence similarity with the
      housefly Rdl subunit in the second membrane-spanning (M2) region. The A274S
      mutation at the -1' position in the M2 region had no effect on [(3)H]EBOB
      binding. The A277S mutation at the 2' position led to a decrease in the affinity
      of EBOB for the GABA receptor. The T281V mutant at the 6' position and the
      A277S/T281V double mutant completely abolished the binding ability. A beta3 GABA
      receptor homology model predicts these interactions between the receptor and
      EBOB. These results suggest that EBOB interacts with threonine 281 and alanine
      277, and that threonine 281 plays a more critical role in interacting with EBOB
      than alanine 277.

PMID- 17205300
TI  - NIPA1 (SPG6) mutations are a rare cause of autosomal dominant spastic paraplegia
      in Europe.

PMID- 17205301
TI  - [Chemically modified, ultra-hydrophilic titanium implant surfaces].
AB  - Recently, a chemically modified ultra-hydrophilic sand-blasted, large grit and
      acid-etched (modSLA) titanium surface has been introduced in order to enhance
      bone apposition. Indeed, preliminary preclinical and clinical data have indicated
      that modSLA implants may enhance bone apposition during early stages of wound
      healing. These positive effects on bone regeneration might be probably mainly due
      to the hydrophilic surface properties noted for modSLA which ensured a
      stabilization of the blood clot. The aim of the present review article is to
      evaluate, based on the currently available evidence, the potential impact of
      modSLA surfaces for implant dentistry.

PMID- 17205302
TI  - [Evaluation of 157 arbitration procedures against maxillofacial surgeons handled
      by the arbitration office of the North German Medical Associations from 2000 to
      2005].
AB  - Medical work is, just like any other profession, not always without error and
      even when no mistake has been made the patient may suffer health damages, because
      such are the unavoidable risks. Arbitration procedures of medical liability
      disputes can in particular cases resolve the individual conflict between
      physician and patient. The results of these arbitration procedures can point
      towards the main focus of diagnosis, patient accusations (patient
      dissatisfaction) and treatment errors. In the space of 6 years from 2000 until
      2005 the North-German arbitration office handled 157 arbitration procedures
      against Maxillofacial surgeons. The decisions were statistically and
      casuistically analysed with regard to patient accusations, type of treatment
      error, frequency of treatment error, health damages that were caused and not
      caused by errors. Liability claims against a physician result only from those
      errors that have caused health damages to a patient. Not all errors cause damage
      automatically. Patient claims were found to be justified in 28% of all procedures
      and a recommendation for regulation was made to the physician's insurance.
      Maxillofacial surgery, with reference to the 20.4% of cases analysed, clearly
      represents less than the total average. The main focus of accusations raised by
      patients and also the main focus of the observed treatment errors are operative
      errors as a cause of sensitivity defects of the lower lip and the tongue, also of
      tongue damages and their associated taste defects. Parallel to the 20.4% of
      cases, which showed iatrogenic health damages caused by errors, 60.9% of cases
      showed patients had also suffered iatrogenic damages even though no medical
      errors had caused them.

PMID- 17205303
TI  - Differential susceptibility of chick and mouse islets to streptozotocin and its
      co-relation with islet antioxidant status.
AB  - Species differences in susceptibility of islets to STZ in different mammals have
      been well documented. Likewise, failure of diabetes induction in birds by
      streptozotocin has been reported. We hypothesized that the susceptibility of
      islets to STZ treatment may be related to generation of reactive oxygen species
      (ROS) and their antioxidant defense mechanisms. To test this hypothesis, we
      measured the total ROS generated and estimated the damage caused to the chick
      islets due to STZ treatment, in terms of lipid peroxidation, protein carbonyl
      formation and DNA strand breaks and compared it with that of mouse islets. We
      also compared the activities of antioxidant enzymes like catalase, superoxide
      dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR) and
      amount of antioxidant molecules like reduced glutathione (GSH) and uric acid
      under control and STZ-treated conditions. These studies coupled with viability,
      functionality and presence of glucose transporter GLUT2 in chick and mouse islets
      clearly indicated that STZ treatment neither affects viability nor functionality
      of chick islets whereas those of mouse islets are affected significantly. Here we
      demonstrate for the first time a correlation between the generation of ROS on STZ
      treatment and antioxidant status with insensitivity of chick islets to STZ
      resulting into failure of diabetes induction in chick.

PMID- 17205304
TI  - Novel paclitaxel formulations for oral application: a phase I pharmacokinetic
      study in patients with solid tumours.
AB  - PURPOSE: To explore the pharmacokinetics (PKs) of paclitaxel and two major
      metabolites after three single oral administrations of a novel drinking solution
      and two capsule formulations in combination with cyclosporin A (CsA) in patients
      with advanced cancer. Moreover, the tolerability and safety of the formulations
      was studied. In addition, single nucleotide polymorphisms in the multidrug
      resistance (MDR1) gene were determined. PATIENTS AND METHODS: Ten patients were
      enrolled and randomized to receive CsA 10 mg/kg followed by oral paclitaxel 180
      mg given as (1) drinking solution (formulation 1), (2) capsule formulation 2B,
      and (3) capsule formulation 2C on day 1, 8, or 15. RESULTS: The median C (max) of
      paclitaxel was 0.42 (0.23-0.96), 0.48 (0.08-0.59), and 0.39 (0.11-1.03) microg/ml
      and the area under the plasma concentration-time curve was 2.83 (1.69-5.12), 2.01
      (1.57-3.04), and 2.67 (1.05-3.61) mug h/ml following administration of
      formulations 1, 2B, and 2C, respectively. The novel formulations were tolerated
      after single oral dose without causing relevant gastrointestinal or
      haematological toxicity. CONCLUSIONS: The PK and metabolism of paclitaxel were
      comparable between the oral formulations co-administered with CsA.

PMID- 17205305
TI  - Localization of proteasomes and proteasomal proteolysis in the mammalian
      interphase cell nucleus by systematic application of immunocytochemistry.
AB  - Proteasomes are ATP-driven, multisubunit proteolytic machines that degrade
      endogenous proteins into peptides and play a crucial role in cellular events such
      as the cell cycle, signal transduction, maintenance of proper protein folding and
      gene expression. Recent evidence indicates that the ubiquitin-proteasome system
      is an active component of the cell nucleus. A characteristic feature of the
      nucleus is its organization into distinct domains that have a unique composition
      of macromolecules and dynamically form as a response to the requirements of
      nuclear function. Here, we show by systematic application of different
      immunocytochemical procedures and comparison with signature proteins of nuclear
      domains that during interphase endogenous proteasomes are localized diffusely
      throughout the nucleoplasm, in speckles, in nuclear bodies, and in nucleoplasmic
      foci. Proteasomes do not occur in the nuclear envelope region or the nucleolus,
      unless nucleoplasmic invaginations expand into this nuclear body. Confirmedly,
      proteasomal proteolysis is detected in nucleoplasmic foci, but is absent from the
      nuclear envelope or nucleolus. The results underpin the idea that the ubiquitin
      proteasome system is not only located, but also proteolytically active in
      distinct nuclear domains and thus may be directly involved in gene expression,
      and nuclear quality control.

PMID- 17205306
TI  - Immunohistochemical localization of advanced glycation end-products (AGEs) and
      their receptor (RAGE) in polycystic and normal ovaries.
AB  - The aim of the present study was to investigate the
      localization/immunohistochemical distribution of AGEs and RAGE, as well as their
      putative signalling mediator NF-kappaB in ovaries of women with polycystic ovary
      syndrome (PCOS) compared to normal. Archival ovarian-tissue samples from biopsies
      of six women with PCOS and from six healthy of similar age women, were examined
      immunohistochemically with monoclonal anti-AGEs, anti-RAGE and anti-NF
      kappaB(p50/p65) specific antibodies. In healthy women, AGE immunoreactivity was
      observed in follicular cell layers (granulosa and theca) and luteinized cells,
      but not in endothelial cells. PCOS specimens displayed AGE immunoexpression in
      theca interna and granulosa cells as well as in endothelial cells, but staining
      of granulosa cells was stronger than in that of normal ovaries. RAGE was highly
      expressed in normal and PCOS tissues. Normal tissue exhibited no staining
      differences between granulosa cell layer and theca interna. However, in PCOS
      ovaries, granulosa cells displayed stronger RAGE expression compared to theca
      interna cells in comparison to controls. NF-kappaB(p50/p65) was expressed in the
      cytoplasm of theca interna and granulosa cells of both normal and PCOS ovaries;
      whereas the NF-kappaB p65 subunit was only observed in granulosa cells nuclei in
      PCOS tissue. In conclusion, these findings demonstrate for the first time that
      RAGE and AGE-modified proteins with activated NF-kappaB are expressed in human
      ovarian tissue. Furthermore, a differential qualitative distribution of AGE, RAGE
      and NF-kappaB p65 subunit was observed in women with PCOS compared to healthy
      controls, where a stronger localization of both AGE and RAGE was observed in the
      granulosa cell layer of PCOS ovaries.

PMID- 17205307
TI  - Expression of androgen receptor and its co-localization with estrogen receptor
      alpha in the developing pituitary gland of sheep fetus.
AB  - No information is known concerning the expression of androgen receptor (AR) and
      its co-localization with estrogen receptor alpha (ERalpha) in the developing
      pituitary of sheep fetus. In the present study, we detected AR expression and its
      co-localization with ERalpha in the anterior pituitary of sheep fetus from day 60
      of gestation to the postnatal by dual immunochemistry. The results showed that
      both AR immunoreactivity (AR-ir) and ERalpha immunoreactivity (ERalpha-ir) were
      predominantly localized in the nuclei of LH positive gonadotropes. The cell
      counting results showed that the percentage of the anterior pituitary cells
      expressing AR fluctuated from 13.51 +/- 0.92 to 17.05 +/- 1.83% during the
      examined stages, but there were no significant differences between sexes and
      among ages examined (P > 0.05). However, the proportion of AR-ir cells containing
      LH markedly increased from day 60 of gestation to the neonatal (P < 0.05). The
      percentage of AR-ir cells expressing ERalpha-ir significantly increased from day
      60 of gestation to the neonatal, respectively (P < 0.05), but no significant
      differences were seen between genders at each stage examined. These results
      indicate that both AR and ERalpha are mainly expressed in the gonadotropes of
      anterior pituitary gland of sheep fetuses, whereas the functions and interaction
      of AR and ERalpha expressions in the developing pituitary gland are required to
      be elucidated further.

PMID- 17205308
TI  - Differentiation-specific association of HP1alpha and HP1beta with chromocentres
      is correlated with clustering of TIF1beta at these sites.
AB  - Mammalian heterochromatin protein 1 (HP1alpha, HP1beta, HP1gamma subtypes) and
      transcriptional intermediary factor TIF1beta play an important role in the
      regulation of chromatin structure and function. Here, we investigated the nuclear
      arrangement of these proteins during differentiation of embryonal carcinoma P19
      cells into primitive endoderm and into the neural pathway. Additionally, the
      differentiation potential of trichostatin A (TSA) and 5-deoxyazacytidine (5
      dAzaC) was studied. In 70% of the cells from the neural pathway and in 20% of TSA
      stimulated cells, HP1alpha and HP1beta co-localized and associated with
      chromocentres (clusters of centromeres), which correlated with clustering of
      TIF1beta at these heterochromatic regions. The cell types that we studied were
      also characterized by a pronounced focal distribution of HP1gamma. The above
      mentioned nuclear patterns of HP1 and TIF1beta proteins were completely different
      from the nuclear patterns observed in the remaining cell types investigated, in
      which HP1alpha was associated with chromocentres while HP1beta and HP1gamma were
      largely localized in distinct nuclear regions. Moreover, a dispersed nuclear
      distribution of TIF1beta was observed. Our findings showed that the nuclear
      arrangement of HP1 subtypes and TIF1beta is differentiation specific, and seems
      to be more important than changes in the levels of these proteins, which were
      relatively stable during all the induced differentiation processes.

PMID- 17205309
TI  - Nucleolar marker for living cells.
AB  - In the recent molecular and cell biological research, there is an increasing need
      for labeling of subcellular structures in living cells. Here, we present the use
      of a fluorescently labeled cell penetrating peptide for fast labeling of nucleoli
      in living cells of different species and origin. We show that the short peptide
      with ten amino acids was able to cross cellular membranes and reach the nucleolar
      target sites, thereby marking this subnuclear structure in living cells. The
      treatment of cells with actinomycin D and labeling of B23 protein and fibrillarin
      provided evidence for a localization to the granular component of the nucleolus.
      The fluorescently conjugated nucleolar marker could be used in combination with
      different fluorophores like fluorescent proteins or DNA dyes, and nucleolar
      labeling was also preserved during fixation and staining of the cells.
      Furthermore, we observed a high stability of the label in long-term studies over
      24 h as well as no effect on the cellular viability and proliferation and on rDNA
      transcription. The transducible nucleolar marker is therefore a valuable
      molecular tool for cell biology that allows a fast and easy labeling of this
      structure in living cells.

PMID- 17205310
TI  - Analysis of urinary calculi using an infrared microspectroscopic surface
      reflectance imaging technique.
AB  - This investigation highlights the use of infrared microspectroscopy for the
      morphological analysis of urinary stones. The research presented here has
      utilized the reflectance mode of an infrared microscope for use in creating
      chemically specific maps of cross-sectioned renal calculi surfaces, precisely
      showing the placement of renal stone components in a calculus sample. The method
      has been applied to renal stones of both single and multiple components
      consisting primarily of hydroxyapatite, calcium oxalate monohydrate and calcium
      oxalate dihydrate. Factors discussed include the photometric accuracy of the
      spectra obtained, a comparison of the surface reflectance method with existing
      methods such as diffuse reflectance infrared Fourier transform spectroscopy
      (DRIFTS) and attenuated total internal reflection (ATR) analysis, and the
      influence of specular reflectance between polished and unpolished sample spectra.
      Full spectral maps of cross-sectioned renal stones provided positive localization
      of components using qualitatively accurate spectra similar in appearance to
      DRIFTS spectra. Unlike ATR and DRIFTS spectra, surface reflectance spectra lack
      photometric accuracy and are therefore not quantifiable; at present, however,
      spectra are suitable for qualitative analysis. It was found that specular
      reflectance increases minimally with a highly polished stone cross-section
      surface, though qualitative data is not affected. Surface reflectance imaging of
      sections of renal stones is useful for determining the identity of stone
      components while simultaneously providing precise locations of mineral components
      within the stone using presently available instruments.

PMID- 17205311
TI  - Regional cerebral blood flow abnormalities in patients with primary
      hyperparathyroidism.
AB  - INTRODUCTION: We assessed the alterations in regional cerebral blood flow (rCBF)
      in patients with primary hyperparathyroidism (PHP) before parathyroidectomy by
      semiquantitative analysis of brain single photon emission computed tomography
      (SPECT) images. METHODS: Included in this prospective study were 14 patients
      (mean age 47.6 +/- 10.4 years; 3 male, 11 female) and 10 control subjects (mean
      age 36.0 +/- 8.5 years, 6 male, 4 female) were SPECT imaging was performed using
      a dual-headed gamma camera 60-90 min after intravenous administration of 925 MBq
      Tc-99m HMPAO. The corticocerebellar rCBF ratios were calculated from 52 brain
      areas and reference lower values (RLVs) were calculated from the rCBF ratios of
      control subjects. The regional ratios that were below the corresponding RLV were
      considered abnormal (hypoperfused). RESULTS: Hypoperfusion was shown in 171 out
      of 728 regions (23%) and there was a significant correlation between serum
      calcium, PTH levels and the sum of hypoperfused regions in the patient group (R =
      0.75 and P = 0.001, and R = 0.75, P = 0.001, respectively). Significantly reduced
      rCBF were found in the following cortical regions: bilateral cingulate cortex,
      superior and inferior frontal cortex, anterior temporal cortex, precentral gyrus,
      postcentral gyrus and parietal cortex, and right posterior temporal cortex.
      CONCLUSION: Our results indicate that alterations in rCBF in patients with PHP
      can be demonstrated with brain SPECT. The correlation between serum calcium, PTH
      levels and the sum of hypoperfused regions indicates that there may be a strong
      relationship between rCBF abnormalities and increased levels of serum calcium and
      PTH. In addition, the degree of rCBF abnormalities could be determined by brain
      SPECT in PHP patients with or without psychiatric symptoms.

PMID- 17205312
TI  - MR neurography with multiplanar reconstruction of 3D MRI datasets: an anatomical
      study and clinical applications.
AB  - INTRODUCTION: Extracranial MR neurography has so far mainly been used with 2D
      datasets. We investigated the use of 3D datasets for peripheral neurography of
      the sciatic nerve. METHODS: A total of 40 thighs (20 healthy volunteers) were
      examined with a coronally oriented magnetization-prepared rapid acquisition
      gradient echo sequence with isotropic voxels of 1 x 1 x 1 mm and a field of view
      of 500 mm. Anatomical landmarks were palpated and marked with MRI markers. After
      MR scanning, the sciatic nerve was identified by two readers independently in the
      resulting 3D dataset. RESULTS: In every volunteer, the sciatic nerve could be
      identified bilaterally over the whole length of the thigh, even in areas of close
      contact to isointense muscles. The landmark of the greater trochanter was falsely
      palpated by 2.2 cm, and the knee joint by 1 cm. The mean distance between the
      bifurcation of the sciatic nerve and the knee-joint gap was 6 cm (+/-1.8 cm). The
      mean results of the two readers differed by 1-6%. CONCLUSION: With the described
      method of MR neurography, the sciatic nerve was depicted reliably and objectively
      in great anatomical detail over the whole length of the thigh. Important
      anatomical information can be obtained. The clinical applications of MR
      neurography for the brachial plexus and lumbosacral plexus/sciatic nerve are
      discussed.

PMID- 17205313
TI  - MR and CT imaging of 24 pleomorphic xanthoastrocytomas (PXA) and a review of the
      literature.
AB  - INTRODUCTION: The aim of our study was to review the imaging appearance of PXA, a
      rare and usually low-grade, astrocytic tumor that typically occurs in young
      adults. METHODS: The clinical presentation, location and imaging findings on CT
      (n = 15) and MR (n = 18) of 24 pathologically confirmed PXA were retrospectively
      reviewed. Two morphologic patterns were defined according to imaging features.
      The Mann-Whitney U-test was used for statistical analysis of the data. RESULTS:
      All the neoplasms were supratentorial and superficial in location with obvious
      leptomeningeal contact in 22 patients, although leptomeningeal enhancement was
      demonstrated in only 3. Common locations were temporal (42%), frontal (33%) and
      parietal (21%), and more than one lobe was involved in 21% of patients. On CT
      without contrast enhancement, PXA was an iso- or hypoattenuating mass, and
      calcification was seen in six tumors and inner table remodeling was seen in three
      patients younger than 12 years. On MR, the solid component of PXA was isointense
      relative to gray matter on T1-weighted images, hyperintense on T2-weighted images
      in more than 90% and enhanced intensely following intravenous contrast material
      administration. Cystic areas showed hyperintensity relative to CSF. Two imaging
      patterns were differentiated: first a cystic mass containing a mural nodule (70%)
      and second a predominantly solid mass that may show cystic changes (30%).
      CONCLUSION: The most consistent imaging features of PXA were a superficial
      location, leptomeningeal contact, and enhancement of the solid component. Apart
      from the classical PXA appearance of a cystic lesion with an enhancing mural
      nodule, a second pattern consisting of a predominantly solid mass was recognized.

PMID- 17205314
TI  - Reversal of flow during carotid artery stenting: use of the Parodi antiembolism
      system.
AB  - INTRODUCTION: To evaluate the flow reversal efficacy of the Parodi antiembolism
      system (PAES) in the prevention of distal emboli during carotid stenting.
      METHODS: A total of 90 patients were treated for internal carotid artery (ICA)
      stenosis with a stent device. A PAES device was used in 31 symptomatic and 5
      asymptomatic patients (total 36 patients) with ICA stenosis, and 54 patients were
      stented without any protection device. Diffusion-weighted (DW) imaging was
      performed before and after stenting. RESULTS: In the group without PAES
      protection, 23 out of 54 patients showed new lesions on DW images after stenting.
      Of the lesions seen, 147 (2.72 lesions/patient) were in the vessel-dependent
      area. In the group with protection, 19 out of 36 patients had new lesions, and
      only 34 (0.94 lesions/patient) were noted in the vessel-dependent area. The
      number of new lesions in the nondependent vessel area did not differ if a
      protection system was used (P = 0.671). The use of PAES led to a significant
      reduction (P = 0.024) in the incidence of the most frequently seen lesions (size
      <2 mm). The stroke death rate was 3.3% overall, 3.7% in the group without
      protection device, and 2.7% in the PAES group. There were no permanent
      neurological deficits after 3 months. CONCLUSION: The PAES is a safe and
      effective tool to reduce the incidence of embolic complications during carotid
      stenting. Older patients and patients with higher grade stenosis seem to profit
      more.

PMID- 17205315
TI  - Unique pharmacological profile of aripiprazole as the phasic component buster.
AB  - RATIONALE: Aripiprazole is a recently introduced antipsychotic with a unique
      pharmacological profile, a dopamine partial agonist. Dopaminergic neural
      transmission has two different components, tonic and phasic, which have different
      physiological functions, but the effects of aripiprazole on tonic and phasic
      components are not reported. OBJECTIVE: Studies on antipsychotics including
      aripiprazole and tonic/phasic dopamine transmission are summarized. RESULTS:
      Antipsychotics exert efficacy without extrapyramidal side effects (EPS's) when
      their occupation of dopamine D2 receptors reaches 65-80%. When a "tightly
      binding" antipsychotic binds 70% of D2 receptors, the remaining 30% are available
      for endogenous dopamine to bind. These tight antipsychotics suppress dopamine
      transmission in both tonic/phasic components equally so that similar proportions
      are kept. Aripiprazole is effective when >90% of D2 receptors are occupied. In
      this condition, less than 10% of D2 receptors are available for endogenous
      dopamine to bind; however, EPS's do not occur because aripiprazole exerts partial
      dopaminergic agonistic activity. Because the concentration of aripiprazole in the
      brain is relatively constant and it binds to D2 receptors tightly, the added
      dopaminergic agonism may show a tonic nature. Thus, aripiprazole suppresses the
      phasic component relatively more than the tonic component. In contrast, under
      treatment with "loosely binding" antipsychotics, phasic dopaminergic transmission
      is relatively preserved. CONCLUSIONS: Tight antipsychotics suppress both tonic
      and phasic components equally. Aripiprazole suppresses the phasic component
      relatively more than the tonic; that is, aripiprazole is a phasic [corrected]
      component buster. By contrast, suppression of the phasic component by loosely
      binding antipsychotics may be relatively weak.

PMID- 17205316
TI  - 5-HT2 receptor mechanisms of the dorsal periaqueductal gray in the conditioned
      and unconditioned fear in rats.
AB  - RATIONALE: It is well known that 5-HT(2) mechanisms modulate the defensive
      behavior produced by the stimulation of the dorsal periaqueductal gray (dPAG).
      However, in spite of the notion that past stressful experiences play a role in
      certain types of anxiety, only studies with the stimulation of the dPAG of rats
      without previous aversive experience have been conducted so far. OBJECTIVES: We
      investigated the mediation of 5-HT(2) receptors of the dPAG in rats previously
      submitted to contextual fear conditioning (CFC). Defensive behaviors induced by
      the activation of the dPAG were assessed by measuring the lowest intensity of
      electric current applied to this structure (threshold) able to produce freezing
      and escape responses during the testing sessions of CFC in which animals were
      placed in a context previously paired to footshocks. The 5-HT(2) function of the
      dPAG in this condition was evaluated by local injections of alpha-methyl-5-HT (20
      nmol/0.2 mul) and ketanserin (5 and 10 nmol/0.2 mul), selective agonist and
      antagonist of 5-HT(2) receptors, respectively. RESULTS: In accordance with
      previous studies, alpha-methyl-5-HT increased the aversive thresholds
      (antiaversive effects) in naive rats, and injection of ketanserin into the dPAG
      did not produce significant effects. On the other hand, ketanserin decreased in a
      dose-dependent manner the freezing threshold (proaversive effect) determined by
      the dPAG electrical stimulation, whereas alpha-methyl-5-HT continued to show
      antiaversive effects in animals under CFC. CONCLUSIONS: The present results
      suggest that past stressful experience can produce changes in the synaptic
      function of 5-HT(2) receptors within the dPAG with important impact on the
      expression of defensive behaviors.

PMID- 17205318
TI  - A double-blind placebo-controlled experimental study of nicotine: II--Effects on
      response inhibition and executive functioning.
AB  - RATIONALE: Smokers may show abnormal functioning in prefrontal cortex during
      acute abstinence, reflecting deficient activity in mesocorticolimbic circuitry.
      Cognitive correlates of this putatively include impaired response inhibition and
      other aspects of executive functioning. OBJECTIVES: To investigate whether
      inhibitory control and other executive functions in smokers are impaired during
      acute abstinence relative to post-nicotine. METHODS: 145 smokers were tested
      twice after overnight abstinence-once after nicotine and once after placebo
      lozenges (order counterbalanced, double-blind)-on an antisaccade task, a
      continuous performance task (CPT), a delayed response spatial working memory task
      and a verbal fluency test. RESULTS: Compared with placebo, nicotine was
      associated with better inhibitory control on the antisaccade task and fewer
      impulsive responses to filler stimuli (motor errors) on the CPT; at the first
      assessment only, nicotine also reduced impulsive responses to 'catch' stimuli on
      the CPT. However, it did not affect CPT response bias (an index of impulsive vs
      cautious decision-making), spatial working memory, or verbal fluency.
      CONCLUSIONS: Smoking abstinence appears to be associated with a difficulty in
      inhibiting prepotent motor responses, and with nicotine to attenuate this
      difficulty. However, more 'cognitive' forms of inhibitory control (e.g. decision
      making) and the other aspects of executive function tested here appear to be
      unaffected.

PMID- 17205317
TI  - The pharmacological management of childhood anxiety disorders: a review.
AB  - RATIONALE: Pediatric anxiety is a prevalent psychiatric disorder that may have
      important implications for school, social, and academic function.
      Psychopharmacological approaches to the treatment of pediatric anxiety have
      expanded over the past 20 years and increasing empirical evidence helps guide
      current clinical practice. OBJECTIVE: To review studies which examine the
      pharmacological treatment of pediatric anxiety disorders, including obsessive
      compulsive disorder and to summarize treatment implications. METHODS: All
      relevant studies were searched using MEDLINE and PsycINFO search engines,
      supplemented by a manual bibliographical search; studies published between 1985
      and 2006 that met inclusion criteria were examined. RESULTS: This article
      provides a systematic review of the psychopharmacological treatment of pediatric
      anxiety disorders based on available empirical evidence, with a focus on
      randomized controlled trials. General treatment principles and pharmacological
      management of specific pediatric anxiety disorders are also reviewed. CONCLUSION:
      There is good evidence to support the efficacy of several pharmacological agents
      including the selective serotonin reuptake inhibitors to treat pediatric anxiety
      and obsessive-compulsive disorder, although there are still many unanswered
      questions.

PMID- 17205319
TI  - Effects of olanzapine, risperidone and haloperidol on sleep after a single oral
      morning dose in healthy volunteers.
AB  - OBJECTIVES: To compare the effects of typical and atypical antipsychotic drugs on
      sleep activity and subjective sleep quality. DESIGN: Randomised, double-blind,
      placebo-controlled, four-period cross-over, clinical trial was used to evaluate
      the effects of active treatments on objective and subjective sleep variables.
      SETTING: Sleep laboratory evaluation. PARTICIPANTS: Twenty healthy young
      volunteers, both sexes. INTERVENTIONS: Single oral morning administrations of
      olanzapine 5 mg, risperidone 1 mg, haloperidol 3 mg and placebo. MEASUREMENTS AND
      RESULTS: Five polysomnographic nights were evaluated: one control night and one
      after each intervention. Significant increase in total sleep time, sleep
      efficiency, slow wave sleep (SWS) and rapid eye movement (REM) sleep with
      decreases in wake time were observed after olanzapine. Decreases in wake time,
      REM sleep and stage shifts together with increases in stage 2 were obtained after
      risperidone. Haloperidol showed only a tendency to increase sleep efficiency and
      stage 2 and to decrease wake time. Olanzapine showed decreases in power density
      in frequencies higher than 10 Hz during all sleep stages and in frequencies lower
      than 5 Hz range in SWS; decreases in the dynamics of spindle frequency activity
      (SFA) in the second and fourth non-rapid eye movement (NREM) episodes were also
      obtained. Risperidone presented increases in the 3.6-10.8 Hz frequency range in
      NREM sleep stages and in stage 2. Haloperidol also showed increases in NREM sleep
      stages and in stage 2, but these were in frequencies higher than 10 Hz, with
      increases in the dynamics of SFA in the first NREM episode. Only a significant
      improvement in subjective sleep quality was observed after olanzapine.
      CONCLUSIONS: Antipsychotics showed different sleep changes as their neurochemical
      profiles were distinct. These changes were observed even when the drug was
      administered 15 h before going to bed.

PMID- 17205320
TI  - Delay discounting predicts cigarette smoking in a laboratory model of abstinence
      reinforcement.
AB  - RATIONALE: Higher rates of delay discounting, or impulsive choice, may be related
      to relapse during abstinence reinforcement interventions for cigarette smoking,
      and a transdermal nicotine patch may attenuate delay discounting. OBJECTIVE: The
      objectives of this study are to assess the relation between delay discounting and
      smoking after nicotine deprivation in a laboratory model of abstinence
      reinforcement and the effects of a transdermal nicotine patch on discounting and
      smoking. MATERIALS AND METHODS: Smokers with no self-reported intention to quit
      were randomly assigned to an active (14 mg) or placebo patch group (n = 15 per
      group). In each of three sessions, after a 3-h deprivation period, participants
      completed a delay discounting task, mood, and craving measures and finally
      engaged in a laboratory model of abstinence reinforcement. Three abstinence
      reinforcement conditions were presented in counterbalanced order across the three
      sessions. During the control session, monetary consequences were delivered every
      30 s regardless of smoking. During the low (5.00 dollars available) and high
      (20.00 dollars available) sessions, participants could earn a progressively
      increasing amount of money for each 30 s period of abstinence. RESULTS: The low
      and high conditions significantly increased the latency to smoke relative to
      control and significantly decreased the amount of smoking. The nicotine patch
      decreased negative affect, but it did not significantly affect delay discounting
      or smoking. Individuals who smoked during the low and high conditions showed
      higher rates of discounting. CONCLUSION: The patch did not attenuate delay
      discounting or smoking after a period of deprivation, but contingencies for
      abstinence significantly decreased smoking. Higher rates of delay discounting
      were related to smoking in a model of abstinence reinforcement treatment.

PMID- 17205321
TI  - Incorrect use of orlistat and sibutramine in clinical practice.
AB  - OBJECTIVE: To investigate how the antiobesity drugs orlistat and sibutramin are
      prescribed in relation to the approved indications and the Swedish subsidiary
      rules. METHODS: Anonymous survey to prescribers of a random sample of 2000 out of
      20,000 prescription of orlistat and sibutramin. RESULTS: The response rate was
      around 65%. About half of the patients were not treated in accordance with the
      approved indications and a fourth of the patients prescribed sibutramin had one
      or several contraindications to the drug. The subsidiary rules were not followed
      in the majority of cases. CONCLUSION: Deviation from the approved indications and
      subsidiary criteria of orlistat and sibutramin is a question of waste of medical
      and economic resources. Prescribing of sibutramin to patients with
      contraindications is a serious health hazard.

PMID- 17205322
TI  - Scientific misconduct.

PMID- 17205323
TI  - [Peripheral pain syndrome].
AB  - The bases for peripheral pain syndromes of the musculoskeletal system, which are
      common and often difficult to treat, involve complex neurophysiologic changes.
      They are generally very troublesome for the patient and result in long-term
      disability and absence from work and sport activities. As all levels of the pain
      perception system are involved, evaluation has to take place at the peripheral,
      spinal and central nervous system levels. Treatment requires a concept including
      all affected structures. If this is not the case, an inefficient series of
      monotherapies often results, which increases the risk of pain chronification in
      these patients similar to the situation found for low back pain. The
      biomechanical-functional aspect is of great importance for the lower extremities.
      This point of view, which is familiar to the orthopedist, reveals a clear
      connection between pain and disturbed function, permitting a clear concept for a
      successful therapy.

PMID- 17205324
TI  - [Clinical pharmacology of analgesics].
AB  - The orthopedist can choose from three classes of drugs to relieve pain.
      Nonsteroidal anti-inflammatory drugs (NSAID) possess sufficient analgetic
      efficacy, but they are hampered by often causing gastrointestinal pain and
      bleeding. Opioids are strong analgetics that can be successfully used against
      strong pain. Their use is limited by spasms in both the gastrointestinal and the
      urinary tract causing constipation and retention of urine, respectively. A
      particular problem is respiratory depression that may be the ultimate cause of
      death in severely ill patients.Among nonacidic analgetics derivatives of pyrazole
      (e.g. dipyrone = metamizole) may also be used in situations associated with
      strong pain. Because of the risk of damage to white blood cells leading to
      agranulocytosis with foudroyant infections their use should be strictly limited
      to conditions that justify such a risk like tumor or colic pain. The aniline
      derivative acetaminophen (= paracetamol) is well tolerated and is the drug of
      choice in usual common pain. Large doses are to be avoided because of liver
      damage, especially in children.

PMID- 17205325
TI  - Heritability and shared environment estimates for myopia and associated ocular
      biometric traits: the Genes in Myopia (GEM) family study.
AB  - To examine the familial correlations, heritability (h(2)) and common
      environmental components (c(2)) of myopia and ocular biometric traits (all
      treated as continuous outcomes) in families collected through the Genes in Myopia
      (GEM) family study in Australia. A total of 132 pedigrees (723 participants) were
      recruited for this study. All individuals completed a risk factor questionnaire
      and underwent a detailed eye examination including spherical equivalent (SphE)
      and ocular biometric measurements of axial length (AL), anterior chamber depth
      (ACD) and corneal curvature (CC). Familial correlations were calculated and h(2)
      and c(2) were estimated using a variance component model that assumes a
      multivariate t distribution within each pedigree. Two definitions of common
      environments (c(2)) were considered: nuclear family (current) shared environment
      (Model 1) and sib-ship (childhood) shared environment (Model 2). Population
      ascertainment adjustment was performed using the Blue Mountains eye study
      dataset. The trends observed for familial correlations suggested that SphE is
      influenced by both environmental and genetic factors whereas AL, ACD and CC are
      predominantly genetically determined. This was largely confirmed by variance
      components modelling. Heritability estimates (adjusted for age, sex and years of
      education) from the best fitting ACE model (Model 2, childhood shared
      environment) were 0.50 +/- 0.05 for SphE, 0.73 +/- 0.04 for AL, 0.78 +/- 0.04 for
      ACD and 0.16 +/- 0.06 for CC. Childhood environmental effects were significant
      with c(2) estimated to be 0.33 +/- 0.04 for SphE, 0.06 +/- 0.03 for AL, 0.22 +/-
      0.04 for ACD and 0.10 +/- 0.05 for CC. Age was associated with SphE, total years
      of education was associated with AL and sex was associated with all traits
      studied. We used a novel and conservative approach to account for and estimate
      common environmental effects by specifying either nuclear family or sib-ship
      environment when estimating heritability estimates and showed that all traits
      examined (SphE, AL, ACD and CC) are heritable, thus reflecting a genetic
      component. These traits therefore all represent candidates for quantitative trait
      linkage analyses.

PMID- 17205326
TI  - The effect of interleukin-1alpha polymorphisms on bone mineral density and the
      risk of vertebral fractures.
AB  - Interleukin-1alpha (IL-1alpha) stimulates bone resorption via osteoclasts.
      Mononuclear cells from patients with osteoporosis show increased IL-1alpha
      production, and IL-1alpha mRNA is more often detected in bone biopsies from
      osteoporotic compared to normal postmenopausal women. Polymorphisms have been
      identified in the IL-1alpha gene; however, none of these has been examined for an
      effect on bone phenotypes in Caucasians. We investigated if the polymorphisms in
      the IL-1alpha gene affect the risk of osteoporotic fractures, bone mineral
      density (BMD), and bone turnover in 462 osteoporotic patients and 336 normal
      controls. Based on previous studies of polymorphisms in the gene and data from
      the International Hap-Map Project, four polymorphisms needed examination in order
      to investigate the effect of known polymorphisms in the IL-1alpha gene. We
      examined C(-1202)-T(rs1800794), C(-889)-T(rs1800587), T(155 + 209)-C(rs2071373),
      C(155 + 320)-T(rs2856838), and G(398)-T(rs 17561) by Taqman and restriction
      fragment-length polymorphism assays. BMD was examined by dual-energy X-ray
      absorptiometry. Bone turnover was evaluated by serum osteocalcin, serum carboxy
      terminal propeptide of human type I procollagen, serum bone-specific alkaline
      phosphatase, serum carboxy-terminal telopeptide of type I collagen, and urinary
      hydroxyproline/creatinine. Genotype distributions were in Hardy-Weinberg
      equilibrium. All polymorphisms were in strong linkage disequilibrium. The C
      allele of the C(155 + 320)-T polymorphism tended to be more common among patients
      with vertebral fractures (P = 0.06) and patients with BMD T score <-2.5 (P =
      0.05). Furthermore, haplotype 1 was associated with reduced risk of having BMD T
      score <-2.5 (P = 0.02). None of the other polymorphisms or haplotypes was
      associated with fracture risk or BMD T score <-2.5. BMD and bone turnover were
      not associated with any of the genetic variants. In conclusion, all the
      polymorphisms within the IL-1alpha gene are in strong linkage disequilibrium and
      not convincingly associated with fracture risk, BMD, or bone turnover.

PMID- 17205327
TI  - Klotho gene polymorphism and male bone mass.
AB  - The Klotho gene codes for a protein that is thought to influence the homeostasis
      of several tissues, including bone, as well as the aging process. Although the
      mechanism of action has not been fully elucidated, some studies in women have
      associated Klotho allelic variants to bone mineral density (BMD). The objective
      of this study was to determine the relationship of a common T/G polymorphism,
      resulting in a phenylalanine (F) to valine (V) substitution, with male bone mass.
      BMD was measured by dual-energy X-ray absorptiometry in 362 Spanish men aged 19
      83 years. Klotho alleles were determined by a Taqman assay. Allele frequencies
      were 85% and 15% for the F and V alleles, respectively. In comparison with the
      most common FF genotype, young and middle-aged men (age less than 53 years) with
      FV/VV genotypes had higher age- and body mass index-adjusted BMD at the lumbar
      spine (1.059 +/- 0.017 vs. 1.016 +/- 0.011 g/cm(2), P = 0.036), the hip (1.077 +/
      0.017 vs. 1.033 +/- 0.011 g/cm(2), P = 0.028), and the calcaneus (0.599 +/-
      0.125 vs. 0.547 +/- 0.108 g/cm(2), P = 0.012). Klotho alleles explained about 2
      4% of BMD variance. However, Klotho genotype was not associated to BMD in older
      men. There were no Klotho-related differences in height, body weight, calcium
      intake, tobacco or alcohol consumption, or serum testosterone levels. In
      conclusion, these results suggest that allelic variants of Klotho constitute one
      of the genetic factors influencing BMD in male adults.

PMID- 17205328
TI  - Clinical determinants of quality of life in Paget's disease of bone.
AB  - Paget's disease of bone (PDB) can adversely affect quality of life, but
      relatively little is known about the clinical predictors of reduced quality of
      life in patients with the disease. Here, we studied quality of life and its
      determinants in a large cohort of PDB patients who had been enrolled into the
      PRISM study, a randomized comparative trial of intensive versus symptomatic
      treatment for PDB. Health-related quality of life was assessed using the Short
      Form 36 (SF36) questionnaire and other validated assessment instruments in 1,324
      subjects with PDB. Clinical predictors of quality of life were identified by
      multivariate regression analysis. The physical summary (mean +/- standard
      deviation) score of the SF36 was substantially reduced in PDB to 36.3 +/- 11.3
      compared with the expected population norm of 50 (P < 0.001). The mental summary
      score was only slightly reduced, to 48.7 +/- 11.8, in PDB; but this was
      statistically significant (P < 0.001). Bone pain due to PDB, previous
      bisphosphonate therapy, and increasing age were identified as negative predictors
      of the SF36 physical summary score (P < 0.001); but serum levels of total
      alkaline phosphatase (ALP) did not predict physical summary score. We conclude
      that PDB has a substantial negative impact on health-related quality of life,
      which mainly affects physical functioning. The lack of correlation between ALP
      and quality of life observed in this study emphasizes the importance of
      addressing quality-of-life issues when treating PDB and not just focussing on
      response of ALP levels.

PMID- 17205329
TI  - Cannabinoids stimulate fibroblastic colony formation by bone marrow cells
      indirectly via CB2 receptors.
AB  - Recently, the cannabinoid receptors CB(1) and CB(2) were shown to modulate bone
      formation and resorption in vivo, although little is known of the mechanisms
      underlying this. The effects of cannabinoids on mesenchymal stem cell (MSC)
      recruitment in whole bone marrow were investigated using either the fibroblastic
      colony-forming unit (CFU-f) assay or high-density cultures of whole bone marrow.
      Levels of the CB(1) and CB(2) receptors were assessed by flow cytometry.
      Treatment of CFU-f cultures with the endocannabinoid 2-arachidonylglycerol (2-AG)
      dose-dependently increased fibroblastic and differentiated colony formation along
      with colony size. The nonspecific agonists CP 55,940 and WIN 55,212 both
      increased colony numbers, as did the CB(2) agonists BML190 and JWH015. The CB(1)
      specific agonist ACEA had no effect, whereas the CB(2) antagonist AM630 blocked
      the effect of the natural cannabinoid tetrahydrocannabivarin, confirming
      mediation via the CB(2) receptor. Treatment of primary bone marrow cultures with
      2-AG stimulated proliferation and collagen accumulation, whereas treatment of
      subcultures of MSC had no effect, suggesting that the target cell is not the MSC
      but an accessory cell present in bone marrow. Subcultures of MSCs were negative
      for CB(1) and CB(2) receptors as shown by flow cytometry, whereas whole bone
      marrow contained a small population of cells positive for both receptors. These
      data suggest that cannabinoids may stimulate the recruitment of MSCs from the
      bone marrow indirectly via an accessory cell and mediated via the CB(2) receptor.
      This recruitment may be one mechanism responsible for the increased bone
      formation seen after cannabinoid treatment in vivo.

PMID- 17205330
TI  - Peripheral bone mineral density and different intensities of physical activity in
      children 6-8 years old: the Copenhagen School Child Intervention study.
AB  - This study aimed to evaluate the association between objectively measured
      habitual physical activity and calcaneal and forearm bone mineral density (BMD,
      g/cm(2)), one mechanically more loaded and one less loaded skeletal region, in
      children aged 6-8 years. BMD was measured in 297 boys and 265 girls by peripheral
      dual-energy X-ray absorptiometry in the forearm and calcaneus. An accelerometer
      registered the level of physical activity during 4 days (2 weekdays and the
      weekend). Weight, height, and skinfold thickness were measured. In order to
      establish thresholds (count . min(-1)) for bone-stimulating physical activity, we
      evaluated different definitions of vigorous physical activity. The boys had 3.2%
      higher distal forearm bone mineral content (BMC, P < 0.001) and 4.5% higher
      distal forearm BMD (P < 0.001) than the girls. They also carried out 9.7% more
      daily physical activity and spent 14.6-19.0% more time in vigorous physical
      activity (all P < 0.05) compared to the girls. In contrast, the girls had 3.8%
      higher calcaneal BMC (P < 0.01) and 2.5% higher calcaneal BMD (P < 0.05) than the
      boys. Both calcaneal and forearm BMD were significantly related to total time of
      daily physical activity as well as with intense physical activity above all the
      chosen cut-off points (all P < 0.05). The beta value for mean count . min(-1)
      physical activity was significantly lower than that for all the chosen cut-off
      points of vigorous activity both for calcaneal and distal forearm BMD. This study
      suggests that both habitual daily physical activity and amount of vigorous
      physical activity in children aged 6-8 years are associated with appendicular
      BMD.

PMID- 17205331
TI  - Quantitative ultrasound in adults with cystic fibrosis: correlation with bone
      mineral density and risk of vertebral fractures.
AB  - In several conditions, including cystic fibrosis (CF) and corticosteroid-induced
      osteoporosis, bone mineral density (BMD) measurements provide a modest prediction
      of fracture risk. We investigated in adult CF patients whether quantitative
      ultrasound (QUS) parameters were able to discriminate between patients with and
      without prevalent vertebral fractures. One hundred seventy-two adults with CF, 91
      men and 81 women, often on chronic oral or inhaled corticosteroid therapy, were
      studied. BMD at the lumbar spine, proximal femur, and total body were measured by
      dual-energy X-ray absorptiometry (DXA). QUS parameters were assessed by Achilles
      Express at the calcaneus and by the DBM Sonic 1200 at the phalanges. All bone
      measurements by DXA and QUS were significantly correlated with each other, with
      the exception of phalangeal amplitude-dependent speed of sound versus spine BMD.
      The mean T-score values in CF patients with and without prevalent vertebral
      fractures were similar for all DXA measurements and for stiffness index. A
      significant difference between the two groups was observed only for phalangeal
      ultrasound bone profile index (UBPI) values (relative risk = 1.25, 95% confidence
      interval 1.05-1.49 for each decrease in T score), and this difference was
      maintained after adjusting the values for age, body weight, forced expiratory
      volume in 1 second, gender, and corticosteroid use. In conclusion, only a
      phalangeal QUS parameter (UBPI), in contrast with calcaneus QUS or DXA
      measurements, was able to discriminate CF patients with from those without
      vertebral fractures, possibly as a result of qualitative alterations of bone
      tissue independent of BMD.

PMID- 17205332
TI  - [Anesthetic incompatibility--rare, but dangerous].

PMID- 17205333
TI  - Agrobacterium-mediated transformation of protocorm-like bodies in Cymbidium.
AB  - Genetically transformed plants of Cymbidium were regenerated after cocultivating
      protocorm-like bodies (PLB) with Agrobacterium tumefaciens strain EHA101
      (pIG121Hm) that harbored genes for beta-glucuronidase (gus), hygromycin
      phosphotransferase (hpt) and neomycin phosphotransferase II (nptII). PLB of three
      genotypes maintained in liquid new Dogashima medium (NDM), were subjected to
      transformation experiments. The PLB inoculated with Agrobacterium produced
      secondary PLB, 4 weeks after transfer onto 2.5 g L(-1) gellan gum-solidified NDM
      containing 10 g L(-1) sucrose, 20 mg L(-1) hygromycin and 40 mg L(-1) meropenem.
      Transformation efficiency was affected by genotype and the presence of
      acetosyringone during cocultivation. The highest transformation efficiency was
      obtained when PLB from the genotype L4 were infected and cocultivated with
      Agrobacterium on medium containing 100 muM acetosyringone. Transformation of the
      hygromycin-resistant plantlets regenerated from different sites of inoculated PLB
      was confirmed by histochemical GUS assay, PCR analysis and Southern blot
      hybridization.

PMID- 17205334
TI  - Genetic transformation of chickpea (Cicer arietinum L.) with insecticidal crystal
      protein gene using particle gun bombardment.
AB  - Here, we report the establishment of an efficient particle gun bombardment
      mediated genetic transformation in chickpea (Cicer arietinum L.) using cryIAc
      gene of Bacillus thuringiensis. Explants were bombarded with recombinant plasmids
      engineered for the expression of cryIAc transgene in plants and stable
      transformants regenerated in presence of benzyladenine, kinetin and kanamycin.
      Transformation frequency showed dependence on explant type, cultivars, plasmids,
      helium pressure and microcarrier type used. Integration of transgenes was
      demonstrated using polymerase chain reaction and Southern blot hybridization
      approaches in T (0) plants. The expression of CryIA(c) delta-endotoxin and GUS
      enzyme was ascertained by enzyme linked immunosorbent assay and histochemical
      assays, respectively. These transgenic plants (T (0)) showed more protection and
      high mortality for Heliothis armigera and Spodoptera litura larvae as compared to
      control plants. The results of the present study indicate that highest
      transformation frequency (18%) could be achieved by use of gold as a microcarrier
      in combination with helium pressure of 900 psi. Among the other factors tested,
      plasmid pHS 102 was the most efficient plasmid, while epicotyl explant was the
      best explant source for particle gun bombardment. Among the different cultivars
      of chickpea tested, cultivar ICCC37 and PG-12 produced higher frequency of
      transformation frequency compared to others.

PMID- 17205335
TI  - Genetic transformation of Arabidopsis lyrata: specific expression of the green
      fluorescent protein (GFP) in pistil tissues.
AB  - Arabidopsis thaliana has become widely used as a model system for plant biology.
      Recent phylogenetic studies led to a severe revision of the systematic
      relationships across species of the Brassicaceae family. This provided an
      opportunity to examine close relatives of A. thaliana and to study the function
      and molecular evolution of genes that play roles in ecology and speciation. In
      this context, developing tools to genetically transform "non-model plants"
      appears as a major issue to ascertain gene function. Here, we report a method to
      transform A. lyrata, one of the closest relatives of A. thaliana.

PMID- 17205336
TI  - A proteinase inhibitor from Nicotiana alata inhibits the normal development of
      light-brown apple moth, Epiphyas postvittana in transgenic apple plants.
AB  - Insecticidal proteins are a potential resource to enhance resistance to insect
      pests in transgenic plants. Here, we describe the generation and analysis of the
      apple cultivar 'Royal Gala' transgenic for Nicotiana alata (N. alata) proteinase
      inhibitor (PI) and the impact of this PI on the growth and development of the
      Epiphyas postvittiana (light-brown apple moth). A cDNA clone encoding a
      proteinase inhibitor precursor from N. alata (Na-PI) under the control of either
      a double 35S promoter or a promoter from a ribulose-1,5-bisphosphate carboxylase
      small sub-unit gene (rbcS-E9 promoter) was stably incorporated into 'Royal Gala'
      apple using Agrobacterium-mediated transformation. A 40.3 kDa Na-PI precursor
      protein was expressed and correctly processed into 6-kDa proteinase inhibitors in
      the leaves of transgenic apple lines. The 6-kDa polypeptides accumulated to
      levels of 0.05 and 0.1% of the total soluble protein under the control of the rbc
      E9 promoter and the double 35S promoter, respectively. Light-brown apple moth
      larvae fed with apple leaves expressing Na-PI had significantly reduced body
      weight after 7 days of feeding and female pupae were 19-28% smaller than
      controls. In addition, morphological changes such as pupal cases attached to the
      wing, deformed wings, deformed body shape, and pupal cases and curled wings
      attached to a deformed body were observed in adults that developed from larvae
      fed with apple leaves expressing Na-PI, when compared to larvae fed with the non
      transformed apple leaves.

PMID- 17205337
TI  - The use of the phosphomannose isomerase gene as alternative selectable marker for
      Agrobacterium-mediated transformation of flax (Linum usitatissimum).
AB  - In order to meet the future requirement of using non-antibiotic resistance genes
      for the production of transgenic plants, we have adapted the selectable marker
      system PMI/mannose to be used in Agrobacterium-mediated transformation of flax
      (Linum usitatissimum L.) cv. Barbara. The Escherichia coli pmi gene encodes a
      phosphomannose isomerase (E.C. 5.1.3.8) that converts mannose-6-phosphate, an
      inhibitor of glycolysis, into fructose-6-phosphate (glycolysis intermediate). Its
      expression in transformed cells allows them to grow on mannose-selective medium.
      The Agrobacterium tumefaciens strain GV3101 (pGV2260) harbouring the binary
      vector pNOV2819 that carries the pmi gene under the control of the Cestrum yellow
      leaf curling virus constitutive promoter was used for transformation experiments.
      Transgenic flax plants able to root on mannose-containing medium were obtained
      from hypocotyl-derived calli that had been selected on a combination of 20 g L(
      1) sucrose and 10 g L(-1) mannose. Their transgenic state was confirmed by PCR
      and Southern blotting. Transgene expression was detected by RT-PCR in leaves,
      stems and roots of in vitro grown primary transformants. The mean transformation
      efficiency of 3.6%, that reached 6.4% in one experiment was comparable to that
      obtained when using the nptII selectable marker on the same cultivar. The ability
      of T1 seeds to germinate on mannose-containing medium confirmed the Mendelian
      inheritance of the pmi gene in the progeny of primary transformants. These
      results indicate that the PMI/mannose selection system can be successfully used
      for the recovery of flax transgenic plants under safe conditions for human health
      and the environment.

PMID- 17205338
TI  - Micropropagation of photinia employing rhizobacteria to promote root development.
AB  - An alternative protocol was developed for in vitro propagation of photinia
      (Photinia x fraseri Dress), an ornamental shrub, using the plant growth-promoting
      rhizobacteria (PGPR) Azospirillum brasilense and Azotobacter chroococcum during
      rhizogenesis. Shoot tips from four-year-old mature plants, cut in spring and
      summer, were used as initial explants. They were cultured on Murashige-Skoog (MS)
      medium with Gamborg's vitamins, N(6)-benzyladenine (BA: 11.1 microM) and
      gibberellic acid (GA(3): 1.3 microM), obtaining 63% of established explants. The
      highest shoot length (22.9 mm) and multiplication rate (4.3) was achieved by
      cultivating for four weeks in the same basal medium supplemented with 4.4 microM
      BA. Both auxin induction and bacterial inoculation were used for rooting.
      Elongated shoots were treated with two concentrations of indole-3-butyric acid
      (IBA: 4.9 or 49.2 microM) during 6 days for auxin induction. Then, the shoots
      were transferred to an auxin-free medium and inoculated with A. brasilense Cd,
      Sp7 or A. chroococcum (local strain). Bacterial inoculation induced earlier
      rooting of photinia shoots. A. brasilense Cd with 49.2 microM IBA pulse showed a
      significant increase (P <or= 0.05) in root fresh and dry weight (105%, 137%),
      root surface area (65%) and shoot fresh and dry weight (32%, 62%). A. brasilense
      Sp7 enhanced the root fresh weight (34%) and root surface area (41%) while no
      significant differences with A. chroococcum inoculation were detected. The PGPR
      inoculated micro-cuttings in combination with auxin induction pulses may play a
      useful role in root organogenesis of micropropagated plants.

PMID- 17205339
TI  - The effects of spacer sequences on silencing efficiency of plant RNAi vectors.
AB  - RNA interference (RNAi) has been used to suppress gene expression in various
      eukaryotic organisms. In plants, RNAi can be induced by introduction of an RNAi
      vector that transcribes a self-complementary hairpin RNA. Most basic RNAi
      constructs have an inverted repeat interrupted with a spacer sequence. To test
      silencing capability of RNAi constructs, we developed an in vivo assay that is
      based on the RNAi-mediated changes of the alpha-linolenic acid content in hairy
      roots. A tobacco endoplasmic reticulum omega-3 fatty acid desaturase (NtFAD3) is
      the main enzyme for production of alpha-linolenic acid of root membrane lipids.
      Tobacco hairy roots transformed with the RNAi vectors against the NtFAD3 gene
      showed a decrease in alpha-linolenic acid content. The frequency of RNA silencing
      was more affected by spacer sequence than by spacer length, at least between 100
      and 1800 bp. Since significant amounts of hairpin RNA against the NtFAD3 gene
      remained in the transgenic plants displaying a weak silencing phenotype, low
      degree of silencing was attributed to low efficiency of hairpin RNA processing
      mediated by Dicer-like proteins. Our results show the possibility of producing a
      broad range of the RNAi-induced silencing phenotypes by replacing the spacer
      sequence of RNAi construct.

PMID- 17205340
TI  - Cytological and molecular characterization of a novel monogenic dominant GMS in
      Brassica napus L.
AB  - A novel genic male sterile (GMS) line in Brassica napus L., which was identified
      in 1999, was found to be controlled by a monogenic dominant gene, which we have
      designated as MDGMS. The microspores of the MDGMS abort before the degradation of
      the tapetal cell layer. The F1 fertility from any fertile lines crossed with
      MDGMS segregated and the ratio was close to 1:1. Bulked segregation analysis
      (BSA) was employed to identify random amplified polymorphic DNA (RAPD) markers
      linked to the Ms gene in MDGMS. Among 880 random 10-mer oligonucleotide primers
      screened against the bulk DNA of sterile and fertile, one primer S243 (5'
      CTATGCCGAC-3') gave a repeatable 1500-bp DNA polymorphic segment S243(1500)
      between the two bulks. Analysis of individual plants of each bulks and other
      types of GMS and cytoplasmic male sterility (CMS) lines suggest that the RAPD
      marker S243(1500) is closely linked to the MDGMS locus in rapeseed. This RAPD
      marker has been converted into sequence characterized amplified region (SCAR)
      marker to aid identification of male-fertility genotypes in segregating progenies
      of MDGMS in marker-assisted selection (MAS) breeding programs.

PMID- 17205341
TI  - In vitro screening of potato against water-stress mediated through sorbitol and
      polyethylene glycol.
AB  - With the objective to develop a practical and effective method of screening
      potato for drought tolerance, shoot and root growth in microtuber-derived
      plantlets was studied in vitro in three genotypes with known root mass production
      under field conditions. Different levels of water-stress were induced using five
      concentrations of either sorbitol or polyethylene glycol (PEG) in MS medium.
      Water potential of various media ranged from -0.80 MPa to -2.05 MPa. Water-stress
      in culture adversely affected plantlet growth, and genotypes differed for their
      responses. Genotype IWA-1 was less affected than IWA-3 and IWA-5. At the same
      level of water potential, sorbitol had lower adverse effect than PEG; the latter
      being sticky. Genotype x sorbitol and genotype x PEG interactions were
      significant. At 0.2 M sorbitol and 0.003 M PEG, IWA-1 had significantly more
      roots with higher total root length, root volume, as well as root-dry weight than
      those of IWA-3 and IWA-5, whereas the latter two genotypes were at par for all
      these characters. This pattern was similar to the reported pattern of these
      genotypes for root-dry weight under field conditions. It is concluded that in
      vitro screening of potato under specific and limited water-stress conditions may
      provide a system for effectively differentiating the genotypes for their expected
      root mass production under field conditions.

PMID- 17205342
TI  - Retransformation of a male sterile barnase line with the barstar gene as an
      efficient alternative method to identify male sterile-restorer combinations for
      heterosis breeding.
AB  - We report in this study, an improved method for identifying male sterile-restorer
      combinations using the barnase-barstar system of pollination control for
      heterosis breeding in crop plants, as an alternative to the conventional line x
      tester cross method. In this strategy, a transgenic male sterile barnase line was
      retransformed with appropriate barstar constructs. Double transformants carrying
      both the barnase and barstar genes were identified and screened for their male
      fertility status. Using this strategy, 66-90% of fertile retransformants
      (restored events) were obtained in Brassica juncea using two different barstar
      constructs. Restored events were analysed for their pollen viability and copy
      number of the barstar gene. Around 90% of the restored events showed high pollen
      viability and approximately 30% contained single copy integrations of the barstar
      gene. These observations were significantly different from those made in our
      earlier studies using line (barnase) x tester (barstar) crosses, wherein only two
      viable male sterile-restorer combinations were identified by screening 88
      different cross-combinations. The retransformation strategy not only generated
      several independent restorers for a given male sterile line from a single
      transformation experiment but also identified potential restorers in the T(0)
      generation itself leading to significant savings in time, cost and labour. Single
      copy restored plants with high pollen viability were selfed to segregate male
      sterile (barnase) and restorer (barstar) lines in the T(1) progeny which could
      subsequently be diversified into appropriate combiners for heterosis breeding.
      This strategy will be particularly useful for crop plants where poor
      transformation frequencies and/or lengthy transformation protocols are a major
      limitation.

PMID- 17205343
TI  - Identification of a 20-bp regulatory element of the Arabidopsis
      pyrophosphate:fructose-6-phosphate 1-phosphotransferase alpha2 gene that is
      essential for expression.
AB  - Arabidopsis harbors two alpha and two beta genes of pyrophosphate:fructose-6
      phosphate 1-phosphotransferase (PFP). The spatial expression patterns of the two
      AtPFPalpha genes were analyzed using transgenic plants containing a promoter::ss
      glucuronidase (GUS) fusion construct. Whereas the AtPFPalpha1 promoter was found
      to be ubiquitously active in all tissues, the AtPFPalpha2 promoter is
      preferentially expressed in specific heterotrophic regions of the Arabidopsis
      plant such as the trichomes of leaves, cotyledon veins, roots, and the stamen and
      gynoecium of the flowers. Serial deletion analysis of the AtPFPalpha2 promoter
      identified a key regulatory element from nucleotides -194 to -175,
      CGAAAAAGGTAAGGGTATAT, which we have termed PFPalpha2 and which is essential for
      AtPFPalpha2 gene expression. Using a GUS fusion construct driven by this 20-bp
      sequence in conjunction with a -46 CaMV35S minimal promoter, we also demonstrate
      that PFPalpha2 is sufficient for normal AtPFPalpha2 expression. Hence, this
      element can not only be used to isolate essential DNA-binding protein(s) that
      control the expression of the carbon metabolic enzyme AtPFPalpha2, but has also
      the potential to be utilized in the production of useful compounds in a specific
      organ such as the leaf trichomes.

PMID- 17205344
TI  - Microhomologies between T-DNA ends and target sites often occur in inverted
      orientation and may be responsible for the high frequency of T-DNA-associated
      inversions.
AB  - Sequence analysis of left and right border integration sites of independent,
      single-copy T-DNA inserts in Arabidopsis thaliana revealed three previously
      unrecognized concomitants of T-DNA integration. First, genomic pre-insertion
      sites shared sequence similarity not only with the T-DNA left and right border
      regions, as was previously reported, but also at high frequency with the inverted
      complement of the T-DNA right border region. Second, palindromic sequences were
      frequently found to overlap or lie adjacent to genomic target sites, suggesting a
      high recombinogenic potential for palindromic elements during T-DNA integration
      and a possible role during the primary contact between the T-DNA and the target
      DNA. Third, "filler" DNA sequences between genomic pre-insertion site DNA and T
      DNA often derive from sequences in the T-DNA left and right border regions that
      are clustered around palindromic sequences in these T-DNA regions, suggesting
      that these palindromic elements are "hot spots" for filler DNA formation. The
      discovery of inverted sequence similarities at the right border suggests a
      previously unrecognized mode of T-DNA integration that involves heteroduplex
      formation at both T-DNA borders and with opposite strands of the target DNA.
      Scanning for sequence similarities in both direct and inverted orientation may
      increase the probability and/or effectiveness of anchoring the T-DNA to the
      target DNA. Variations on this scheme may also account for inversion events at
      the target site of T-DNA integration and inverted T-DNA repeat formation, common
      sequence organization patterns associated with T-DNA integration.

PMID- 17205346
TI  - [The management of cutaneous metastases].
AB  - Cutaneous metastases are rare and usually signify a poor prognosis. The
      manifestation of cutaneous metastases is variable; crucial to their diagnosis is
      their inclusion in the differential diagnosis. The therapy occurs mostly with
      palliative intention. The quality of life of the patient should take first
      priority. A combination chemotherapy is usually carried out because of systemic
      progress. For local tumor control and wound care, metastasis surgery and
      radiotherapy are used.

PMID- 17205347
TI  - Routine use of FDG-PET scans in melanoma patients with positive sentinel node
      biopsy.

PMID- 17205349
TI  - Sacral chordoma: a diagnosis not to be sat on?
AB  - Sacral chordomas are rare, slow-growing tumours that are amenable to surgery, but
      unfortunately often diagnosed late. The aim of the study was to identify
      presenting symptoms, which may aid diagnosis and reduce the treatment time. Forty
      four patients were identified with sacral chordoma between 1989 and 2006.
      Clinical and pathological records were reviewed retrospectively to elicit the
      symptoms recorded prior to diagnosis, duration of symptoms, surgical treatment,
      size of tumour and survival. Eleven patients were excluded, leaving 33 patients
      in the study group. Thirty-one patients had chordomas arising from the sacrum and
      two patients from the coccyx. The mean duration of symptoms prior to diagnosis
      was 120 weeks (2.3 years), with a median of length of 104 weeks (two years) and
      range of 26 to 416 weeks (0.5 to eight years). The mean maximum tumour size at
      resection was 8.3 cm, with a mean volume of 614 cm(3) (range 9-2,113 cm(3)).
      Pain, typically dull and worse with sitting, was the most common presenting
      symptom in 85% of patients. The classic symptoms of cauda equina (saddle
      anaesthesia, bladder or bowel dysfunction) occurred in 70% patients (23
      patients). Sacral chordoma should be considered in cases of back pain with
      coccydynia, especially with neurological symptoms.

PMID- 17205350
TI  - Construction of the astaxanthin biosynthetic pathway in a methanotrophic
      bacterium Methylomonas sp. strain 16a.
AB  - Methylomonas sp. strain 16a is an obligate methanotrophic bacterium that uses
      methane or methanol as the sole carbon source. An effort was made to engineer
      this organism for astaxanthin production. Upon expressing the canthaxanthin gene
      cluster under the control of the native hps promoter in the chromosome,
      canthaxanthin was produced as the main carotenoid. Further conversion to
      astaxanthin was carried out by expressing different combinations of crtW and crtZ
      genes encoding the beta-carotenoid ketolase and hydroxylase. The carotenoid
      intermediate profile was influenced by the copy number of these two genes under
      the control of the hps promoter. Expression of two copies of crtZ and one copy of
      crtW led to the accumulation of a large amount of the mono-ketolated product
      adonixanthin. On the other hand, expression of two copies of crtW and one copy of
      crtZ resulted in the presence of non-hydroxylated carotenoid canthaxanthin and
      the mono-hydroxylated adonirubin. Production of astaxanthin as the predominant
      carotenoid was obtained in a strain containing two complete sets of carotenoid
      biosynthetic genes. This strain had an astaxanthin titer ranging from 1 to 2.4 mg
      g(-1) of dry cell biomass depending on the growth conditions. More than 90% of
      the total carotenoid was astaxanthin, of which the majority was in the form of E
      isomer. This result indicates that it is possible to produce astaxanthin with
      desirable properties in methanotrophs through genetic engineering.

PMID- 17205351
TI  - The role of computed tomography in terminal ballistic analysis.
AB  - Terminal ballistics concerns the science of projectile behaviour within a target
      and includes wound ballistics that considers what happens when a projectile
      strikes a living being. A number of soft tissue ballistic simulants have been
      used to assess the damage to tissue caused by projectiles. Standard assessment of
      these materials, such as ballistic soap or ordnance gelatine, requires the block
      to be opened or that a mould to be made to visualize the wound track. This is
      time consuming and may affect the accuracy of the findings especially if the
      block dries and alters shape during the process. Therefore, accurate numerical
      analysis of the permanent or temporary cavity is limited. Computed tomography
      (CT) potentially offers a quicker non-invasive analysis tool for this task. Four
      commercially purchased ballistic glycerine soap blocks were used. Each had a
      single firearm discharged into it from a distance of approximately 15 cm using
      both gunshot and shotgun projectiles. After discharge, each block was imaged by a
      modern 16 slice multi-detector CT scanner and analysed using 3-D reconstruction
      software. Using the anterior-posterior and lateral scout views and the multi
      plane reconstructed images, it was possible to visualize the temporary cavity, as
      well as the fragmentation and dispersal pattern of the projectiles, the distance
      travelled and angle of dispersal within the block of each projectile or fragment.
      A virtual cast of the temporary cavity can be also be made. Multi-detector CT
      with 3-D analysis software is shown to create a reliable permanent record of the
      projectile path allowing rapid analysis of different firearms and projectiles.

PMID- 17205352
TI  - Susceptibility to infection by a haemogregarine parasite and the impact of
      infection in the Australian sleepy lizard Tiliqua rugosa.
AB  - The Hamilton and Zuk hypothesis on haemoparasite-mediated sexual selection and
      certain studies of fitness are based on the assumption that blood parasite
      infections are detrimental to their hosts. However, there are few reports that
      have demonstrated harmful effects of endemic blood parasites on fitness in wild
      populations, and it has even been suggested that they may be non-pathogenic. In
      this paper, we show that individuals of the Australian sleepy lizard (Tiliqua
      rugosa) have smaller home ranges when they are infected with the haemogregarine
      blood parasite Hemolivia mariae than when no infection can be detected. An
      apparently contradictory result was that lizards with larger home ranges were
      more susceptible to infection under experimental exposure to Hemolivia. We
      propose that lizards sacrifice defence against pathogens by increased activity,
      perhaps associated with maintaining home ranges and mating opportunities. As a
      consequence, they gain higher parasite loads, which in turn inhibit their
      activity. In this case, the parasite-host interaction may act as a buffer of
      lizard activity.

PMID- 17205353
TI  - Sacculogenesis and sporogony of Tetracapsuloides bryosalmonae (Myxozoa:
      Malacosporea) within the bryozoan host Fredericella sultana (Bryozoa:
      Phylactolaemata).
AB  - Tetracapsuloides bryosalmonae is the myxozoan parasite responsible for
      proliferative kidney disease (PKD) of salmonid fishes. This disease affects
      farmed species in North America and Western Europe where it results in
      significant economic losses for the rainbow trout industry. The parasite has two
      hosts in its life cycle, salmonid fish, and freshwater bryozoans. In this study,
      we describe the development of the parasite at the ultrastructural level within
      the bryozoan host Fredericella sultana. Single celled, presaccular stages form
      aggregates within the metacoel of this host which resolve into spore sacs. Within
      these sacs sporogenesis is initiated with the differentiation of presporogonic
      cells into sporogonic and valvogenic cells. These latter cells surround a
      sporogonic cell which subsequently divides to form a sporoplasmogenic cell and a
      capsulogenic cell. The capsulogenic cell divides further to form four cells each
      with a polar capsule, while the sporoplasmogenic cell divides resulting in four
      cells, two primary cells and two secondary cells. The secondary cells are
      engulfed by the primary cells resulting in a mature sporoplasm. It is
      hypothesized that autogamy occurs during the initial formation of the spore sac
      and that allogamy is also possible during this time.

PMID- 17205354
TI  - Serine-401 as a batrachotoxin- and local anesthetic-sensing residue in the human
      cardiac Na+ channel.
AB  - Sequence alignment of four S6 segments in the human cardiac Na+ channel suggests
      that serine-401 (hNav1.5-S401) at D1S6 along with asparagine-927 (N927) at D2S6,
      serine-1458 (S1458) at D3S6, and phenylalanine-1760 (F1760) at D4S6 may jointly
      form a pore-facing S(401)N(927)S(1458)F(1760) ring. Importantly, this pore-facing
      structure is adjacent to the putative gating-hinge (G(400)G(926)G(1457)S(1759))
      and close to the selectivity filter. Within this SNSF ring, only S401 has not yet
      been identified as a batrachotoxin (BTX) sensing residue. We therefore created
      S401 mutants with 12 substitutions (S401C,W,P,A,K,F,R,E,L,N,D,G) and assayed
      their BTX sensitivity. All S401 mutants expressed Na+ currents but often with
      altered gating characteristics. Ten mutants were found sensitive to 5 muM BTX,
      which eliminated Na+ channel fast inactivation after repetitive pulses. However,
      S401K and S401R became BTX resistant. In addition, the block of open and
      inactivated hNav1.5-S401K Na+ channels by local anesthetic bupivacaine was
      reduced by approximately 8-10-fold, but not the block of resting Na+ channels.
      Qualitatively, these ligand-sensing phenotypes of hNav1.5-S401K channels resemble
      those of S1458K and F1760K channels reported earlier. Together, our results
      support that residue hNav1.5-S401 at D1S6 is facing the inner cavity and is in
      close proximity to the receptor sites for BTX and for local anesthetics.

PMID- 17205355
TI  - Odor and pheromone detection in Drosophila melanogaster.
AB  - Drosophila melanogaster has proven to be a useful model system to probe the
      mechanisms underlying the detection, discrimination, and perception of volatile
      odorants. The relatively small receptor repertoire of 62 odorant receptors makes
      the goal of understanding odor responses from the total receptor repertoire
      approachable in this system, and recent work has been directed toward this goal.
      In addition, new work not only sheds light but also raises more questions about
      the initial steps in odor perception in this system. Odorant receptor genes in
      Drosophila are predicted to encode seven transmembrane receptors, but surprising
      data suggest that these receptors may be inverted in the plasma membrane compared
      to classical G-protein coupled receptors. Finally, although some Drosophila
      odorant receptors are activated directly by odorant molecules, detection of a
      volatile pheromone, 11-cis vaccenyl acetate requires an extracellular adapter
      protein called LUSH for activation of pheromone sensitive neurons. Because
      pheromones are used by insects to trigger mating and other behaviors, these
      insights may herald new approaches to control behavior in pathogenic and
      agricultural pest insects.

PMID- 17205356
TI  - Ciliary calcium signaling is modulated by kidney injury molecule-1 (Kim1).
AB  - Primary cilia have been shown to play an important role in embryonic development
      as well as in postnatal life. Dysfunctional cilia are associated with situs
      inversus, retinal abnormalities, impaired mucociliary clearance, infertility,
      hydrocephalus, and congenital renal cysts. In autosomal dominant polycystic
      kidney disease, mutations of the ciliary proteins polycystin1 or the transient
      receptor potential (TRP) channel family protein polycystin2 (TRPP2) cause
      progressive cyst formation and destruction of the kidney. Primary cilia act as
      flow sensors and respond to flow-mediated bending with a prolonged intracellular
      calcium increase, which appears to require an intact polycystin protein complex.
      We have established a novel flow chamber system, which allows us to study renal
      epithelial cells by live cell imaging. We show that MDCK cells respond to flow by
      a delayed increase in intracellular calcium and that this response requires these
      cells to be ciliated. We show that a novel interactor of TRPP2, kidney injury
      molecule-1 (Kim1), which is expressed at low levels in the normal kidney and
      upregulated after ischemia, in renal cell cancer and in PKD is targeted to
      primary cilia when stably expressed in MDCK cells. We demonstrate that expression
      of tyrosine mutant Kim1, lacking a conserved tyrosine in the intracellular tail,
      abolishes the calcium increase in response to flow in a dominant negative manner.
      These results establish Kim1 as a novel regulatory molecule of flow-induced
      calcium signaling.

PMID- 17205357
TI  - Costs versus benefits: best possible and best practical treatment regimens for
      HIV.
AB  - Current HIV therapy, although highly effective, may cause very serious side
      effects, making adherence to the prescribed regimen difficult. Mathematical
      modeling may be used to evaluate alternative treatment regimens by weighing the
      positive results of treatment, such as higher levels of helper T cells, against
      the negative consequences, such as side effects and the possibility of resistance
      mutations. Although estimating the weights assigned to these factors is
      difficult, current clinical practice offers insight by defining situations in
      which therapy is considered "worthwhile". We therefore use clinical practice,
      along with the probability that a drug-resistant mutation is present at the start
      of therapy, to suggest methods of rationally estimating these weights. In our
      underlying model, we use ordinary differential equations to describe the time
      course of in-host HIV infection, and include populations of both activated CD4(+)
      T cells and CD8(+) T cells. We then determine the best possible treatment
      regimen, assuming that the effectiveness of the drug can be continually adjusted,
      and the best practical treatment regimen, evaluating all patterns of a block of
      days "on" therapy followed by a block of days "off" therapy. We find that when
      the tolerance for drug-resistant mutations is low, high drug concentrations which
      maintain low infected cell populations are optimal. In contrast, if the tolerance
      for drug-resistant mutations is fairly high, the optimal treatment involves
      periods of reduced drug exposure which consequently boost the immune response
      through increased antigen exposure. We elucidate the dependence of the optimal
      treatment regimen on the pharmacokinetic parameters of specific antiviral agents.

PMID- 17205358
TI  - Treatment of a hepatic artery aneurysm by endovascular stent-grafting.
AB  - Aneurysms of the visceral arteries are rare. Traditional treatment has been
      surgical or endovascular with coil embolization. Recently, however, reports on
      endovascular therapy with stent-grafts have been published. We report the case of
      a 61-year-old man who was successfully treated with a stent-graft for a
      symptomatic combined celiac/hepatic artery aneurysm.

PMID- 17205359
TI  - Onyx, a new liquid embolic material for peripheral interventions: preliminary
      experience in aneurysm, pseudoaneurysm, and pulmonary arteriovenous malformation
      embolization.
AB  - PURPOSE: To describe our preliminary experience with a new liquid embolization
      agent, Onyx, in peripheral interventions. METHODS AND RESULTS: We successfully
      treated two peripheral aneurysms (one in an internal iliac artery, one in a
      thoracic collateral artery of an aortic coarctation), two peripheral
      pseudoaneurysms (one in a lumbar artery, one in a renal artery), and one
      pulmonary arteriovenous malformation. CONCLUSION: Onyx is a promising alternative
      embolic material for peripheral interventions. It can be combined with coils in
      selected cases, and balloon catheters can be effectively used during slow
      injection of embolic material to control flow and protect the aneurysm neck.

PMID- 17205360
TI  - Air embolism detected during computed tomography fluoroscopically guided
      transthoracic needle biopsy.
AB  - Air embolism is a rare but potentially fatal complication of percutaneous needle
      biopsy of the lung. We report a case of cerebral air embolism which occurred
      during computed tomography (CT)-guided needle biopsy. Air entering the aorta is
      depicted on CT-fluoroscopy images of the procedure.

PMID- 17205361
TI  - Results of a peripheral cutting balloon prospective multicenter European registry
      in hemodialysis vascular access.
AB  - PURPOSE: To report initial experience with the Peripheral Cutting Balloon (PCB)
      in treatment of failing hemodialysis shunts. METHODS: A total of 190 patients (95
      men, 95 women; average age 64.4 +/- 11.9 years, range 32-87 years) who were
      treated with the PCB for pressure-resistant stenosis, restenosis or failed
      percutaneous transluminal angioplasty (PTA) in the venous limb of an
      arteriovenous shunt were followed in seven European centers using a simple
      registry. The group consisted of 109 de novo lesions (57%) and 79 restenotic
      lesions (43%). RESULTS: Technical success was achieved in 88.9% of cases. Primary
      patency was as follows (the results for whole group and simultaneous results for
      de novo lesions and restenoses are presented): 1 month (140 patients followed):
      94%, 98%, and 93%; 3 months (116 patients followed): 93%, 98%, and 92%; 6 months
      (40 patients followed): 85%, 92%, and 79%; 12 months (27 patients followed): 74%,
      87%, and 48%. No complication occurred. Patients experienced an equal or lower
      level of pain during the procedure compared with conventional PTA. CONCLUSION:
      The PCB proved to be successful in dilating pressure-resistant stenoses. We
      cannot conclude whether PCB angioplasty can lower the restenosis rate in
      hemodialysis access lesions, but the long-term patency for de novo lesions is
      high. A further randomized study is advisable.

PMID- 17205362
TI  - Percutaneous transcatheter ethanol sclerotherapy and catheter drainage of
      postoperative pelvic lymphoceles.
AB  - The aim of this study is to investigate the efficacy and long-term results of
      percutaneous transcatheter ethanol sclerotherapy (PTES) for postoperative pelvic
      lymphocele treatment. Fifty-two patients who were referred for lymphocele
      treatment were included in this study. Sixty lymphoceles of 52 patients were
      treated by percutaneous treatment with or without ethanol sclerotherapy.
      Lymphoceles developed in 47 and 5 patients, who underwent gynecologic malignancy
      operation (31 ovarian cancer, 6 cervix cancer, 10 endometrial cancer) and renal
      transplantation, respectively. Lymphoceles were catheterized by ultrasonography
      and fluoroscopy guidance using the Seldinger technique. Lymphoceles smaller than
      150 mL underwent single-session ethanol sclerotherapy and the others were treated
      by multiple-session ethanol sclerotherapy. In 10 patients, percutaneous ethanol
      sclerotherapy could not be performed and they were treated only by percutaneous
      catheter drainage. The mean lymphocele volume was 329 mL (15-2900 mL). The mean
      catheterization duration was 11.8 days (1-60 days). The mean follow up time was
      25.8 months (2-64 months). The initial treatment was successful in 46 out of 50
      (91%) lymphoceles treated with PTES and 7 out of 10 (70%) lymphoceles treated
      with percutaneous catheter drainage. Minor complications (secondary infection and
      catheter dislodgement) were noted in seven (11.6%) patients. Recurrence developed
      in four and three patients who were treated by PTES and percutaneous catheter
      drainage, respectively. Five of these patients were treated with PTES without
      further recurrence. Percutaneous transcatheter ethanol sclerotherapy is an
      effective and reliable method for the treatment of postoperative lymphoceles.

PMID- 17205363
TI  - Transvenous embolization of a spontaneous femoral AVF 5 years after an incomplete
      treatment with arterial stent-grafts.
AB  - A 66-year-old man with complex left femoral arterio-venous fistula (AVF) was
      first diagnosed after a deep venous thrombosis incident approximately 5 years
      ago. Partial treatment was performed by means of endografts along the superficial
      femoral artery, which remained patent for 5 years. The patient had been doing
      well until a couple of months ago when he developed severe venous stasis and
      ulcers of the left cruris, due to a high-flow nonhealing complex AVF with
      additional iliac vein occlusion. Therefore; the definitive treatment was
      performed by a unique endovascular technique combined with surgical venous bypass
      (femoro-femoral crossover saphenous bypass, the Palma operation). A novel
      percutaneous transvenous technique for occlusion of a complex high-flow AVF is
      reported with a review of the literature. The case is unique with spontaneous
      AVF, transvenous embolization with detachable coils and ONYX, and the hybrid
      treatment technique as well as the long-term patency of superficial femoral
      artery stent-grafts.

PMID- 17205364
TI  - Evaluation of retrievability of the Gunther tulip vena cava filter.
AB  - PURPOSE: To evaluate the feasibility and safety of withdrawal of a Gunther tulip
      retrievable vena cava filter (GTF). METHODS: Between June 2001 and December 2005,
      at our institution 86 GTFs were implanted for temporary caval filtration in 59
      patients (37 women, 22 men; mean age 59.3 years, range 18-87 years). For GTFs
      retrieved thereafter, we retrospectively reviewed the following parameters: rate
      of success in retrieval, degree of trapped thrombus in the filter, and
      complications during retrieval. RESULTS: Worsening of or new development of
      pulmonary embolism after filter implantation did not occur in any patient. Of the
      86 GTFs implanted, retrieval of 80 was attempted. Among those 80 filters, 77
      (96%) were successfully retrieved (with the standard method, n = 72; with the
      modified method, n = 5) without any complication. The period of implantation of
      the retrieved filters was 13.4 +/- 4.2 days. In the 5 filters that were filled to
      a height of > or = 1/4 with trapped thrombus, retrieval was performed after
      attempts were made to decrease trapped thrombi. In addition, a temporary filter
      or another GTF was temporarily placed at the cephalad level of the GTF during
      this removal procedure. CONCLUSION: GTFs can be retrieved in the majority of
      cases. Even when encountering situations in which the filter could not be removed
      using the standard method, withdrawal was possible in a high frequency of cases
      through various trials using modified methods.

PMID- 17205365
TI  - Successful percutaneous transluminal angioplasty and stenting in acute mesenteric
      ischemia.
AB  - Acute mesenteric ischemia (AMI) is a life-threatening emergency. The
      complications are high by the time of diagnosis in most cases and therefore only
      few data on primary percutaneous intervention with percutaneous transluminal
      angioplasty (PTA) and stenting in AMI are available. We present the case of an 84
      year-old woman who presented to our emergency department complaining of an acute
      worsening of pre-existing abdominal periumbilical pain, nausea, vomiting, and
      diarrhea. She had previously undergone percutaneous transluminal embolectomy for
      an acute occlusion of the left common femoral artery. Due to suspicion of
      intestinal infarction, conventional angiography of the aorta and the superior
      mesenteric artery (SMA) was performed and confirmed a proximal occlusion of the
      SMA. Percutaneous SMA recanalization with balloon dilation and subsequent stent
      implantation was carried out successfully. The abdominal symptoms subsided after
      this procedure. In AMI that is diagnosed early, endovascular stenting should be
      considered as an alternative treatment to the surgical approach that avoids the
      need for surgical bowel resection.

PMID- 17205366
TI  - Contrast-enhanced ultrasound in detection and follow-up of an infrarenal
      abdominal aortic aneurysm with aorto-caval fistula and endovascular treatment.
AB  - An aorto-caval fistula is a rare complication of a symptomatic or ruptured
      infrarenal aortic aneurysm having a frequency of 3-6%. Patients typically present
      with clinical signs of diffuse abdominal pain associated with increasing venous
      congestion and tachycardia, rapid cardiopulmonary decompensation with acute
      dyspnea, and an audible machinerylike bruit. Perioperative mortality is high,
      ranging from 20% to 60%. We report a case of an endovascular aortic repair in a
      patient with a symptomatic infrarenal aortic aneurysm and an aorto-caval fistula.
      Contrast-enhanced ultrasound seems to be a promising new diagnostic option for
      the diagnosis and preoperative treatment planning for patients with abdominal
      aortic aneurysms with rupture into the inferior vena cava. It is in addition to
      computed tomography angiography. It might allow a more rapid and noninvasive
      diagnosis, especially for patients in intensive care because of its bedside
      availability. Because the examination is dynamic, additional information about
      blood flow between the aorta and inferior cava vein can be evaluated.

PMID- 17205367
TI  - A weight index for the standardized uptake value in 2-deoxy-2-[F-18]fluoro-D
      glucose-positron emission tomography.
AB  - INTRODUCTION: Known errors in the standardized uptake value (SUV) caused by
      variations in subject weights W encountered can be corrected by lean body mass or
      body surface area (bsa) algorithms replacing W in calculations. However this is
      infrequently done. The aims of the work here are: quantify sensitivity to W,
      encourage SUV correction with an approach minimally differing from tradition, and
      show what improvements in the SUV coefficient of variation (cv) for a population
      can be expected. METHODS: Selected for analyses were 2-deoxy-2-[F-18]fluoro-D
      glucose (FDG) SUV data from positron emission tomography (PET) and PET/computed
      tomography (CT) scans at the University of Tennessee as well as from the
      literature. A weight sensitivity index was defined as -n=slope of ln(SUV/W) vs.
      lnW. The portion of the SUV variability due to this trend is removed by using the
      defined [formula: see text], or a virtually equal SUVm using [formula: see text],
      with Q and ID being tissue specific-activity and injected dose. [formula: see
      text] measures performance. Adapting to animal studies' tradition, [formula: see
      text] is preferred over the conventional [formula: see text]. RESULTS: For FDG in
      adults [formula: see text] from averaging over most tissues. In children,
      however, [formula: see text]. Tissues have the same index if their influx
      constants are independent of W. Suggested, therefore, is a very simplified
      [formula: see text], which is dimensionless and keeps the same population
      averages as traditional SUVs. It achieves [formula: see text]. Hence, for cv's of
      SUVs below approximately 1/3 improvements over tradition are possible, leading to
      F's<0.95. Accounting additionally for height, as in SUVbsa, gives very little
      improvement over the simplified approach here and gives essentially the same F's
      as SUVm. CONCLUSIONS: Introduced here is a weight index useful in reducing
      variability and further understanding the SUV. Addressing weight sensitivity is
      appropriate where the cv of the SUVs is below about 1/3. Proposed is the very
      simple approach of using an average of an adult patient's weight and
      approximately 70 kg for FDG SUV calculations. Unlike other approaches the
      dimensionless population average of SUVms is unchanged from tradition.

PMID- 17205368
TI  - Scrotal bladder hernia: report of two cases.
AB  - Two new cases of scrotal bladder hernia (SBH) are presented. The first patient
      developed leakage of urine from the wound after "hydrocele" surgery. Revision of
      the wound showed a defect in the bladder wall. The bladder was separated from
      hernias sutures and closed in two layers. In the second, obese patient with a
      right scrotal swelling and two-stage voiding SBH was recognized preoperatively.
      The peritoneal sac and bladder wall were separately sutured and herniotomy was
      performed. The history, clinical features, pathology and treatment of SBH are
      summarized. The literature is briefly reviewed.

PMID- 17205369
TI  - Intravesical Cu-T emigration: an atypical and infrequent cause of vesical
      calculus.
AB  - Transuterine transvesical emigration of an intrauterine contraceptive device is a
      rare and uncommonly described complication of an intrauterine device. We report
      and describe the clinical outcome and management of one such case of intravesical
      intrauterine device that had become calcified leading to the erroneous diagnosis
      of a vesical calculus. The diagnosis was confirmed after cystoscopic
      visualization, lithoclasty and extraction of the calcified plaque consisting of
      the Cu-T. A migrated IUD is a rare and infrequent cause for the formation of
      secondary vesical calculi. The treating surgeon should be aware of the
      possibility of such episodic cases of vesical calculi occurring in the women
      presenting with recurrent unexplained urinary sepsis.

PMID- 17205370
TI  - Spontaneous rupture and emergency repairment of the renal pelvis.
AB  - A case of spontaneous rupture of the renal pelvis is very rare and unusual
      occurrence. Our case was a young woman who did not present with any disease that
      was a factor for pelvic rupture. The diagnosis was confirmed by abdominopelvic
      CT, and emergency repair of the renal pelvis was performed and a ureteral stent
      was inserted. Appropriate antibiotherapy was ordered, and the recovery was rapid.
      The differential diagnosis of this ease is discussed and the literature is
      reviewed:

PMID- 17205371
TI  - Scrotal extension of emphysematous pyelonephritis.
AB  - We report an extensive form of emphysematous pyelonephritis (EPN) in the right
      kidney extending from the anterior abdominal wall to the scrotum in a patient
      with renal calculi with obstructive uropathy and describe the progression route
      of infection from retroperitoneum to scrotum. Such an extensive occurrence of EPN
      is very rare. The patient succumbed after 48 h despite aggressive treatment.

PMID- 17205372
TI  - Life threatening hypokalemia and quadriparesis in a patient with
      ureterosigmoidostomy.
AB  - We report quadriparesis as a result of severe hypokalemia and acidosis in a 15
      years-old young man who had undergone ureterosigmoidostomy for bladder extrophy 3
      months earlier. The patient was initially mistakenly diagnosed to be a case of
      Guillain-Barre syndrome. On investigations acidosis and profound hypokalemia were
      present. Dramatic improvement occurred after correction of hypokalemia and
      acidosis with intravenous potassium and bicarbonate. The underlying mechanism as
      well as the treatment of hyperchloremic metabolic acidosis and hypokalemia after
      ureterosigmoidostomy are hereby discussed.

PMID- 17205373
TI  - Evaluation of machine-learning methods for ligand-based virtual screening.
AB  - Machine-learning methods can be used for virtual screening by analysing the
      structural characteristics of molecules of known (in)activity, and we here
      discuss the use of kernel discrimination and naive Bayesian classifier (NBC)
      methods for this purpose. We report a kernel method that allows the processing of
      molecules represented by binary, integer and real-valued descriptors, and show
      that it is little different in screening performance from a previously described
      kernel that had been developed specifically for the analysis of binary
      fingerprint representations of molecular structure. We then evaluate the
      performance of an NBC when the training-set contains only a very few active
      molecules. In such cases, a simpler approach based on group fusion would appear
      to provide superior screening performance, especially when structurally
      heterogeneous datasets are to be processed.

PMID- 17205374
TI  - Feature-map vectors: a new class of informative descriptors for computational
      drug discovery.
AB  - In order to develop robust machine-learning or statistical models for predicting
      biological activity, descriptors that capture the essence of the protein-ligand
      interaction are required. In the absence of structural information from X-ray or
      NMR experiments, deriving informative descriptors can be difficult. We have
      developed feature-map vectors (FMVs), a new class of descriptors based on
      chemical features, to address this challenge. FMVs, which are derived from the
      conformational models of a few actives, are low dimensional, problem specific,
      and highly interpretable. By using shape-based alignments and scoring with
      chemical features, FMVs can combine information about a molecule's shape and the
      pharmacophores it can match. In five validation studies, bag classifiers built
      using FMVs have shown high enrichments for identifying actives for five diverse
      targets: CDK2, 5-HT(3), DHFR, thrombin, and ACE. The interpretability of these
      descriptors has been demonstrated for CDK2 and 5-HT(3), where the method
      automatically discovers the standard literature pharmacophore.

PMID- 17205375
TI  - First evidence of methylation in the genome of Drosophila willistoni.
AB  - DNA methylation has been studied abundantly in vertebrates and recent evidence
      confirms that this phenomenon could be disseminated among some invertebrates
      groups, including Drosophila species. In this paper, we used the Methylation
      Sensitive Restriction Endonuclease (MSRE) technique and Southern blot with
      specific probes, to detect methylation in the Drosophila willistoni species. We
      found differential cleavage patterns between males and females that cannot be
      explained by Mendelian inheritance, pointing to a DNA methylation phenomenon
      different from the Drosophila melanogaster one. The sequencing of some of these
      bands showed that these fragments were formed by different DNA elements, among
      which rDNA. We also characterized the D. willitoni dDnmt2 sequence, through a
      Mega Blast search against the D. willistoni Trace Archive Database using the D.
      melanogaster dDnmt2 nucleotide sequence as query. The complete analysis of D.
      willistoni dDnmt2 sequence showed that its promoter region is larger, its dDnmt2
      nucleotide sequence is 33% divergent from the D. melanogaster one, Inverted
      Terminal Repeats (ITRs) are absent and only the B isoform of the enzyme is
      produced. In contrast, ORF2 is more conserved. Comparing the D. willistoni and D.
      melanogaster dDnmt2 protein sequences, we found higher conservation in motifs
      from the large domain, responsible for the catalysis of methyl transfer, and
      great variability in the region that carries out the recognition of specific DNA
      sequences (TRD). Globally, our results reveal that methylation of the D.
      willistoni genome could be involved in a singular process of species-specific
      dosage compensation and that the DNA methylation in the Drosophila genus can have
      diverse functions. This could be related to the evolutionary history of each
      species and also to the acquisition time of the dDnmt2 gene.

PMID- 17205376
TI  - Oximetry feedback flow control simulation for oxygen therapy.
AB  - OBJECTIVES: For many with Chronic Obstructive Pulmonary Disease (COPD), arterial
      oxygen saturation while receiving Long-Term Oxygen Therapy (LTOT) falls below an
      acceptable threshold (SpO(2) < 90%) for extended periods during routine daily
      activities. Using a closed-loop controller, we have evaluated a simulated method
      to automatically regulate the oxygen flow-rate in response to the measured oxygen
      demand. METHODS: The closed-loop control scheme was implemented in a computer
      simulation on Simulink. Feedback from a pulse oximeter was used to maintain a
      target SpO(2) of 91% by changing the oxygen flow-rate to the patient. The
      controller was evaluated using a model to approximate the patient's arterial
      oxygen saturation response, including hypoxic events from artificial disturbances
      as well as recorded patient oximetry data. RESULTS: The simulated controller
      produced improvement in arterial oxygen saturation throughout a wide range of
      disturbance frequencies. It suppressed disturbances with periods greater than a
      couple of minutes by more than -10 dB. When evaluated with patient oximetry
      recordings, the controller on average reduced the time spent with arterial blood
      saturation below threshold by 76%. Given the same volume of oxygen, the closed
      loop controller also produced a 63% improvement compared to fixed flow-rate LTOT.
      CONCLUSIONS: The simulation findings indicate an optimized matching between
      oxygen supply and demand, maintaining SpO(2) above threshold to improve
      therapeutic efficacy compared to standard LTOT.

PMID- 17205377
TI  - Genotyping of phenotypically defined cells in neoplasia: enhanced immunoFISH via
      tyramide signal amplification (TSA) segregates immunophenotypically-defined cell
      populations for gated genotyping.
AB  - Molecular morphologic tools exist for simultaneously visualizing immunophenotype
      and genotype of tumors, but are frequently hampered by a delicate balance between
      removing sufficient amount of the protein blocking full access of the probe to
      hybridize to target nucleic acids while still preserving sufficient target
      antigen for immunophenotyping. The result is often suboptimal, with either
      insufficiently visualized gene deletions and amplifications due to masking
      protein, or overdigestion of the protein target. Our purpose was to design and
      validate a gated genotyping assay that enables optimal and concomitant detection
      of both gene and protein. Using the proliferating endothelial cell compartment
      within gliomas organized in a tissue microarray (TMA), we tested the hypothesis
      that tyramide signal amplification (TSA) with deposition of a fluorochrome could
      be used during immunophenotyping, permitting sufficient protein digestion while
      insuring probe accessibility to nucleic acid target. The method was successfully
      validated using a TMA containing 38 glioma cases previously genotyped for EGFR
      amplification. CD31 positive endothelial cells were segregated via TSA-based
      Alexa-Fluor 647 immunofluorescence for analysis of EGFR amplification of the
      gliomas organized in the TMA. Enhanced immunoFISH (TSA) successfully segregates
      immunophenotypically-defined cell populations for gated genotyping.

PMID- 17205379
TI  - Candida gelsemii sp. nov., a yeast of the Metschnikowiaceae clade isolated from
      nectar of the poisonous Carolina jessamine.
AB  - A new yeast species, Candida gelsemii, is described to accommodate three isolates
      recovered in Georgia, USA, from the toxic nectar of the Carolina jessamine
      (Gelsemium sempervirens). The species resembles other members of the
      Metschnikowiaceae clade that have been recovered from nectar, but differs in a
      number of morphological and physiological characteristics. Analysis of rDNA
      sequences places the new species well into the clade, but in a basal position
      with respect to a group of Metschnikowia and Candida species known to occur in
      association with nectars and bees, as well as marine invertebrates. The type is
      strain UWOPS 06-24.1(T) (CBS 10509(T), NRRL Y-48212(T).

PMID- 17205380
TI  - Introducing "I wish I knew then ...".

PMID- 17205381
TI  - The tissue bank at the Instituto Nacional de Investigaciones Nucleares: ISO
      9001:2000 certification of its quality management system.
AB  - Tissue banking is a complex operation concerned with the organisation and
      coordination of all the steps, that is, from donor selection up to storage and
      distribution of the final products for therapeutic, diagnostic, instruction and
      research purposes. An appropriate quality framework should be established in
      order to cover all the specific methodology as well as the general aspects of
      quality management, such as research and development, design, instruction and
      training, specific documentation, traceability, corrective action, client
      satisfaction, and the like. Such a framework can be obtained by developing a
      quality management system (QMS) in accordance with a suitable international
      standard: ISO 9001:2000. This paper presents the implementation process of the
      tissue bank QMS at the Instituto Nacional de Investigaciones Nucleares in Mexico.
      OBJECTIVE: The objective of the paper is to share the experience gained by the
      tissue bank personnel [radiosterilised tissue bank (BTR)] at the Instituto
      Nacional de Investigaciones Nucleares (ININ, National Institute of Nuclear
      Research), during implementation of the ISO 9001:2000 certification process. At
      present, the quality management system (QMS) of ININ also complies with the
      Mexican standard NMX-CC-9001:2000. The scope of this QMS is Research, Development
      and Processing of Biological Tissues Sterilised by Gamma Radiation, among others.

PMID- 17205382
TI  - Effects of gamma irradiation on mechanical properties of defatted trabecular bone
      allografts assessed by speed-of-sound measurement.
AB  - New sterilization methods for human bone allografts may lead to alterations in
      bone mechanical properties, which strongly influence short- and medium-term
      outcomes. In many sterilization procedures, bone allografts are subjected to
      gamma irradiation, usually with 25 KGy, after treatment and packaging. We used
      speed-of-sound (SOS) measurements to evaluate the effects of gamma irradiation on
      bone. All bone specimens were subjected to the same microbial inactivation
      procedure. They were then separated into three groups, of which one was treated
      and not irradiated and two were exposed to 10 and 25 KGy of gamma radiation,
      respectively. SOS was measured using high- and low-frequency ultrasound beams in
      each orthogonal direction. SOS and Young modulus were altered significantly in
      the three groups, compared to native untreated bone. Exposure to 10 or 25 KGy had
      no noticeable effect on the study variables. The impact of irradiation was small
      compared to the effects of physical or chemical defatting. Reducing the radiation
      dose used in everyday practice failed to improve graft mechanical properties in
      this study.

PMID- 17205383
TI  - Developing a simplified river landscape assessment model: examples from the
      Chungkang and Touchien rivers, Taiwan.
AB  - Currently, river landscape evaluations cannot be conducted by the general public,
      due to their lack of professional training. However, consulting professionals is
      time consuming and costly. The research conducted addresses both problems by (1)
      developing suitable criteria for assessing river environments, and (2)
      formulating a strategy for using the proposed criteria, thereby creating an
      effective method for river management by non-professionals. This research was
      carried out, in accordance with Visual Resource Management theory, at 12 survey
      sites along the ChungKang River. The landscape quality sequences acquired were
      then evaluated using a revised and simplified assessment model. The same process
      was repeated on the Touchien River to verify its feasibility. This research
      developed both specific criteria as well a method for evaluating river
      landscapes, which can be employed by non-professional river project managers.
      Ultimately, the aim of this research is to develop and promote sustainable river
      resource management.

PMID- 17205384
TI  - Generation of an improved cytogenetic and comparative map of Bos taurus
      chromosome BTA27.
AB  - Comparative genome analysis in cattle, human, and mouse identified various
      evolutionary breakpoints between Bos taurus 27 chromosome (BTA27) and
      corresponding segments in the Homo sapiens 4 and 8 chromosomes (HSA4, HSA8) and
      the Mus musculus 8 chromosome (MMU8). The fragmentary cytogenetic location of
      breaks is based on nine known loci and Zoo-FISH data on BTA27. A comparative
      mapping approach combining in-silico mapping and physical mapping by fluorescence
      in-situ hybridization (FISH) revealed an improved cytogenetic map of BTA27 based
      on 25 new and nine existing assignments of loci. Furthermore, hybrid cell mapping
      techniques identified and anchored three additional gene loci on BTA27. The BTA27
      map was compared with available mapping and annotated sequence data for the
      chromosome and a generated comparative map displays conserved syntenic chromosome
      blocks between cattle, human, and mouse. The new anchor loci identify and narrow
      down evolutionary breakpoints on a cytogenetic level and can help to support the
      cattle genome assembly and annotation process.

PMID- 17205385
TI  - Chromosome maps of legumes.
AB  - Legumes are of immense importance as food and feed, and for sustainable
      agriculture, due to their ability to fix nitrogen. Here, the chromosome maps of
      the legumes soybean (Glycine max), Lotus (Lotus japonicus), and red clover
      (Trifolium pratense) are reviewed. These species have relatively small
      chromosomes and therefore are difficult to exploit for chromosome studies.
      Nevertheless, the identification of individual chromosomes became feasible, and
      chromosome maps have been developed applying image analysis and fluorescence in
      situ hybridization. For Lotus japonicus, e.g. detailed chromosome maps have been
      developed using the information of genetic linkage maps. Future prospects of
      further legume chromosome mapping for breeding and genetic purposes are
      discussed.

PMID- 17205386
TI  - Complex emotions, complex problems: understanding the experiences of perinatal
      depression among new mothers in urban Indonesia.
AB  - In this article, we explore how Javanese women identify and speak of symptoms of
      depression in late pregnancy and early postpartum and describe their subjective
      accounts of mood disorders. The study, conducted in the East Java region of
      Indonesia in 2000, involved in-depth interviews with a subgroup of women (N = 41)
      who scored above the cutoff score of 12/13 on the Edinburgh Postnatal Depression
      Scale (EPDS) during pregnancy, at six weeks postpartum, or on both occasions.
      This sample was taken from a larger cohort study (N cohort = 488) researching the
      sociocultural factors that contribute to women's emotional well-being in early
      motherhood. The women used a variety of Indonesian and Javanese terms to explain
      their emotional states during pregnancy and in early postpartum, some of which
      coincided with the feelings described on the EPDS and others of which did not.
      Women attributed their mood variations to multiple causes including: premarital
      pregnancy, chronic illness in the family, marital problems, lack of support from
      partners or family networks, their husband's unemployment, and insufficient
      family income due to giving up their own paid work. We argue for the importance
      of understanding the context of childbearing in order to interpret the meaning of
      depression within complex social, cultural, and economic contexts.

PMID- 17205387
TI  - Successful neoadjuvant synchronous chemo- and radiotherapy for disseminated
      primary intracranial choriocarcinoma: case report.
AB  - We report a 17-year-old male with disseminated intracranial choriocarcinoma at
      the basal ganglia whose consciousness level was very low at diagnosis. He
      received neoadjuvant therapy (NAT) consisting of combined chemo- and radiotherapy
      prior to radical excision of the tumor. Postoperatively he was treated with three
      courses of high-dose chemotherapy (carboplatin (CBDCA), methotrexate (MTX), and
      etoposide (VP-16)) and peripheral blood stem-cell transplantation. This
      combination of therapies resulted in tumor regression on MRI and remarkable
      improvement in his neurological condition. Ours is the first report of the
      effectiveness of NAT followed by radical surgery in a patient with disseminated
      primary intracranial choriocarcinoma.

PMID- 17205388
TI  - Marantic endocarditis (NBTE) with systemic emboli and paraneoplastic cerebellar
      degeneration: uncommon presentation of ovarian cancer.
AB  - We report a case in which the only presenting symptoms of the underlying ovarian
      malignancy were that of paraneoplastic cerebellar degeneration and nonbacterial
      thrombotic endocarditis. If suspecting paraneoplastic cerebellar degeneration and
      nonbacterial thrombotic endocarditis, complete physical examination, including
      pelvic exams in female patients is warranted. Investigations should include CT
      chest/abdominal/pelvis, MRI brain, and Transesophageal Echocardiogram. Early
      recognition will lead to early diagnosis of occult malignancy and initiation of
      appropriate therapy. Awareness of these complications as initial presentation for
      internists, gynecologists and neurologists may avoid diagnostic delay.

PMID- 17205389
TI  - Strategies to reduce HIV risk behavior in HIV primary care clinics: brief
      provider messages and specialist intervention.
AB  - Reducing HIV transmission is a critical goal worldwide, prompting new strategies
      to slow the spread of the virus. This paper describes the theoretical
      underpinnings of the Comprehensive Harm Reduction Protocol (CHRP) and the process
      of its implementation in one large urban HIV clinic and two smaller rural primary
      care clinics. Patients enrolled in CHRP complete the Risk Diagnostic
      Questionnaire (RDQ), self-reporting HIV transmission risk behavior at most clinic
      visits. Clinicians review RDQs to trigger dialogue using motivational
      interviewing and the stages of health behavior change to reduce high-risk
      behaviors (drug use, alcohol use, or high-risk sexual behavior). In the ongoing
      evaluation study, CHRP patients receive two provider-only visits before being
      randomized to continue with provider brief prevention messages only or to receive
      additional intensive counseling with a risk-reduction specialist following the
      provider visit. If outcome data support one or both interventions, CHRP could be
      a useful model for widespread adoption. Observations from the implementation of
      this protocol are presented in order to facilitate the adoption of this protocol
      in interested clinics. Later, results of the evaluation of the implementation of
      the protocol may have value in developing prevention policy in HIV treatment
      clinics.

PMID- 17205390
TI  - Effects of levetiracetam in lipid peroxidation level, nitrite-nitrate formation
      and antioxidant enzymatic activity in mice brain after pilocarpine-induced
      seizures.
AB  - : Oxidative stress has been implicated in a large number of human degenerative
      diseases, including epilepsy. Levetiracetam (LEV) is a new antiepileptic agent
      with broad-spectrum effects on seizures and animal models of epilepsy. Recently,
      it was demonstrated that the mechanism of LEV differs from that of conventional
      antiepileptic drugs. Objectifying to investigate if LEV mechanism of action
      involves antioxidant properties, lipid peroxidation levels, nitrite-nitrate
      formation, catalase activity, and glutathione (GSH) content were measured in
      adult mice brain. The neurochemical analyses were carried out in hippocampus of
      animals pretreated with LEV (200 mg/kg, i.p.) 60 min before pilocarpine-induced
      seizures (400 mg/kg, s.c.). The administration of alone pilocarpine, 400 mg/kg,
      s.c. (P400) produced a significant increase of lipid peroxidation level in
      hippocampus. LEV pretreatment was able to counteract this increase, preserving
      the lipid peroxidation level in normal value. P400 administration also produced
      increase in the nitrite-nitrate formation and catalase activity in hippocampus,
      beyond a decrease in GSH levels. LEV administration before P400 prevented the
      P400-induced alteration in nitrite-nitrate levels and preserved normal values of
      catalase activity in hippocampus. Moreover, LEV administration prevented the P400
      induced loss of GSH in this cerebral area. The present data suggest that the
      protective effects of LEV against pilocarpine-induced seizures can be mediated,
      at least in part, by reduction of lipid peroxidation and hippocampal oxidative
      stress.

PMID- 17205391
TI  - Antibodies to a nonconjugated prion protein peptide 95-123 interfere with PrP( Sc
      ) propagation in prion-infected cells.
AB  - 1. Vaccination-induced anti-prion protein antibodies are presently regarded as a
      promising approach toward treatment of prion diseases. Here, we investigated the
      ability of five peptides corresponding to three different regions of the bovine
      prion protein (PrP) to elicit antibodies interfering with PrP(Sc) propagation in
      prion-infected cells.2. Rabbits were immunized with free nonconjugated peptides.
      Obtained immune sera were tested in enzyme-linked immunosorbent assay (ELISA) and
      immunoblot for their binding to recombinant PrP and cell-derived pathogenic
      isoform (PrP(Sc)) and normal prion protein (PrP(c)), respectively. Sera positive
      in all tests were chosen for PrP(Sc) inhibition studies in cell culture.3. All
      peptides induced anti-peptide antibodies, most of them reacting with recombinant
      PrP. Moreover, addition of the serum specific to peptide 95-123 led to a
      transient reduction of PrP(Sc) levels in persistently prion-infected cells.4.
      Thus, anti-PrP antibodies interfering with PrP(Sc) propagation were induced with
      a prion protein peptide nonconjugated to a protein carrier. These results point
      to the potential application of the nonconjugated peptide 95-123 for the
      treatment of prion diseases.

PMID- 17205392
TI  - Effects of opioid blockade with naltrexone and distraction on cold and ischemic
      pain in hypertension.
AB  - Essential hypertension is characterised by reduced pain sensitivity. Hypertensive
      hypoalgesia has been attributed to elevated endogenous opioids and/or increased
      activation of descending pain modulation systems. A double-blind placebo
      controlled design compared the effects of naltrexone and placebo on cold and
      ischemic pain in unmedicated newly-diagnosed patients with essential
      hypertension. Patients performed a cold pressor task while resting and while
      performing a distracting secondary task. They also performed a forearm ischemia
      task while resting. Although the cold pressor and ischemia tasks elicited
      significant increases in pain and blood pressure, pain ratings and pressor
      responses did not differ between naltrexone and placebo. Cold pain was reduced by
      distraction compared to rest. The finding that opioid blockade with naltrexone
      did not moderate the pain and pressor responses to cold and ischemia suggests
      that pain and associated blood pressure responses are not modulated by opioids in
      hypertension. The finding that the distracting secondary task successfully
      reduced pain ratings suggests normal supraspinal pain modulation in essential
      hypertension.

PMID- 17205393
TI  - Multivariate Cholesky models of human female fertility patterns in the NLSY.
AB  - Substantial evidence now exists that variables measuring or correlated with human
      fertility outcomes have a heritable component. In this study, we define a series
      of age-sequenced fertility variables, and fit multivariate models to account for
      underlying shared genetic and environmental sources of variance. We make
      predictions based on a theory developed by Udry [(1996) Biosocial models of low
      fertility societies. In: Casterline, JB, Lee RD, Foote KA (eds) Fertility in the
      United States: new patterns, new theories. The Population Council, New York]
      suggesting that biological/genetic motivations can be more easily realized and
      measured in settings in which fertility choices are available. Udry's theory,
      along with principles from molecular genetics and certain tenets of life history
      theory, allow us to make specific predictions about biometrical patterns across
      age. Consistent with predictions, our results suggest that there are different
      sources of genetic influence on fertility variance at early compared to later
      ages, but that there is only one source of shared environmental influence that
      occurs at early ages. These patterns are suggestive of the types of gene-gene and
      gene-environment interactions for which we must account to better understand
      individual differences in fertility outcomes.

PMID- 17205394
TI  - Morphological analogies in Hebrew-speaking university students with dyslexia
      compared with typically developing gradeschoolers.
AB  - Little attention has been devoted to date to the study of morphological knowledge
      in individuals with developmental dyslexia. The current study compares the
      ability of Hebrew-speaking adult dyslexic students and gradeschool children to
      analyze written words into their morphological components, using a linguistic
      analogy task. Two sets of monolingual Hebrew-speaking participants--152 typically
      developing gradeschool children and 38 undergraduate students diagnosed with
      reading disabilities--were administered the Morphological Analogies Task. Results
      indicate an early ability of normally developing children to perform
      morphological analogies, while the adult dyslexic group performed on par with 3rd
      and 4th grade. Error analysis revealed that the overwhelming majority of the
      erroneous responses in all grades involved morphological strategies rather than
      the associative semantic strategy. However, the adult dyslexic students had many
      more associative responses than the graderschoolers. This testifies to the
      reduced written morphological abilities of adult dyslexic students.

PMID- 17205396
TI  - Identification and biochemical studies on novel non-nucleoside inhibitors of the
      enzyme adenosine kinase.
AB  - The enzyme adenosine kinase (AK) plays a key role in the regulation of
      intracellular and extracellular concentration of adenosine (Ado), which exhibits
      potent hormonal activity in cardiovascular, nervous and immune systems. In view
      of the pharmacological effects of Ado, there is much interest in identifying
      inhibitors of AK, which can augment its tissue-protective effects. In this study,
      we have screened 1040 compounds from a chemical library of putative kinase
      inhibitors for their effect on purified human recombinant AK. These studies have
      identified 8 novel, non-nucleoside AK inhibitors. Four of these compounds (viz. 2
      tert-butyl-4H-benzo[1,2,4]thiadiazine-3-thione (2759-0749); N-(5,6-diphenyl
      furo[2,3-d]pyrimidin-4-yl)-propionamide (3998-0118); 3-[5,6-Bis-(4-methoxy
      phenyl)-furo[2,3-d]pyrimidin-4-ylamino]-propan-1-ol (4072-2732); and 2-[2-(3,4
      dihydroxy-phenyl)-5-phenyl-1H-imidazol-4-yl]-fluoren-9-one (8008-6198)), which
      inhibited human AK in a concentration-dependent manner in a low micromolar range
      (IC(50) = 0.38 approximately 1.98 microM) were further studied. Kinetic and
      structural studies on these compounds provide evidence that inhibition of AK by
      these compounds was competitive with respect to Ado and non-competitive for ATP.
      All of these compounds also inhibited uptake of Ado and its metabolism in
      cultured mammalian cells at comparable concentrations indicating their efficient
      cellular penetrability. These AK inhibitors, whose chemical structures differ
      significantly from all previously known inhibitors, provide useful lead compounds
      for identification of more potent but less toxic AK inhibitors that may prove
      useful for therapeutic purposes.

PMID- 17205397
TI  - An irreversible and kinetically controlled process: thermal induced denaturation
      of L-2-hydroxyisocaproate dehydrogenase from Lactobacillus confusus.
AB  - The thermal denaturation of Lactobacillus confusus L-2-Hydroxyisocaproate
      Dehydrogenase (L-HicDH) has been studied by Differential Scanning Calorimetry
      (DSC). The stability of this enzyme has been investigated at different pH
      conditions. The results of this study indicate that the thermal denaturation of
      this enzyme is irreversible and the T(m) is dependent on the scan-rate, which
      suggests that the denaturation process of L-HicDH is kinetically determined. The
      heat capacity function of L-HicDH shows a single peak with the T(m) values
      between 52.14 degrees C and 55.89 degrees C at pH 7.0 at different scan rates.
      These results indicate that the whole L-HicDH could unfold as a single
      cooperative unit, and intersubunit interactions of this homotetrameric enzyme
      must play a significant role in the stabilization of the whole enzyme. The rate
      constant of the unfolding is analyzed as a first order kinetic constant with the
      Arrhenius equation, and the activation energy has been calculated. The variation
      of the activation energy values obtained with different methods does not support
      the validity of the one-step irreversible model. The denaturation pathway was
      described by a three-state model, N --> U --> F, in which the dissociation of the
      tetramer takes place as an irreversible step before the irreversible unfolding of
      the monomers. The calorimetric enthalpy associated with the irreversible
      dissociation and the calorimetric enthalpy associated with the unfolding of the
      monomer were obtained from the best fitting procedure. Thermal unfolding of L
      HicDH was also studied using Circular Dichroism (CD) spectroscopy. Both methods
      yielded comparable values.

PMID- 17205398
TI  - Stigmatization of overweight Mexican children.
AB  - The present study was designed to determine the weight-based stigmatization of
      Mexican overweight (OW) and non-OW children by their mothers and peers, who rated
      both boys and girls with varying physical characteristics. Four hundred and
      thirty-two fifth and sixth graders and 342 mothers participated in the study.
      Children were administered a questionnaire displaying six drawings. Participants'
      responses were numbered in order of preference from 1 to 6 (most to least well
      liked). Participants were divided into categories based on socioeconomic status,
      ethnicity, and current body mass index. The majority of children chose the child
      in a wheelchair as the preferred friend. Boys and girls, Indian and non-Indian,
      with and without risk of OW chose the obese peer as the least-preferred friend.
      Non-OW girls and their mothers liked the obese child less than non-OW boys and
      their mothers. Agreement correlations between mothers and children were rho =
      0.19 (P = 0.0001), rho = 0.17 (P = 0.001), and rho = 0.13 (P = 0.02) for the
      healthy child, child with missing arm, and obese child, respectively. There was a
      strong correlation between Indian mothers and non-OW daughters (rho = 0.54, P =
      0.009) on choosing the drawing of the obese child as the least preferred friend.
      These data suggest an influential effect of the negative attitude of mothers
      toward the obese child, which are projected to their children.

PMID- 17205400
TI  - Prone to pregnancy: Orlando, Virginia Woolf and Sally Potter represent the
      gestating body.
AB  - The visibility of pregnancy in contemporary societies through various forms of
      medical imaging has often been interpreted by feminist critics as negative for
      the autonomy and experience of pregnant women. Here, I consider the
      representation of pregnancy in Virginia Woolf's novel, Orlando, and Sally
      Potter's film of the same name arguing that, despite limited critical attention
      to Orlando's pregnancy, these texts offer a productive interpretation of
      gestation that counters conventionally reductive cultural images of that embodied
      state. In particular, I argue that Potter's translation of Woolf's novel to the
      screen gives us a useful model for thinking through the new visibility of
      pregnancy in contemporary Western culture.

PMID- 17205399
TI  - Human pancreatic digestive enzymes.
AB  - A primary function of the pancreas is to produce digestive enzymes that are
      delivered to the small intestine for the hydrolysis of complex nutrients. Much of
      our understanding of digestive enzymes comes from studies in animals. New
      technologies and the availability of the sequence of the human genome allow for a
      critical review of older reports and assumptions based on animal studies. This
      report updates our understanding of human pancreatic digestive enzymes with a
      focus on new insights into the biology of human proteases, lipases and amylases.

PMID- 17205401
TI  - Temperament and character in pathological gambling.
AB  - OBJECTIVE: We have studied temperament and character in pathological gambling
      (PG). METHODS: Thirty-eight DSM-IV verified pathological gamblers (31 males and 7
      females; mean age 35.4 +/- 10.4 years) were tested with Cloninger's Temperament
      and Character Inventory (TCI). Matched controls were chosen from the normal
      population. RESULTS: Pathological gamblers scored higher on the temperament
      factors novelty seeking (NS) and harm avoidance (HA). The most pronounced
      difference was found in the character factor self-directedness (SD). The
      pathological gamblers differed from controls in cooperativeness and self
      transcendence. A personality disorder was found in 29% of the pathological
      gamblers 84% of whom scored either low on SD and high on impulsivity or had a
      more dishonest behaviour. Two-thirds of pathological gamblers showed immature
      character with or without high HA in temperament. The other third showed normal
      character extravagant behaviour (86%), high impulsivity (36%) and less
      responsibility (50%) being the most common personality traits. CONCLUSION: HA and
      NS might be trait-like characteristics in PG.

PMID- 17205402
TI  - Controversial issues in the management of echinococcal liver disease.

PMID- 17205403
TI  - Assessment of bone metabolism and mineral density in chronic viral hepatitis.
AB  - BACKGROUND/AIMS: The aim of the study was to assess bone metabolism and impact of
      disease on bone mineral density in patients with non-cirrhotic chronic hepatitis
      B or C. METHODS: 105 patients with chronic hepatitis B or C receiving antiviral
      agents and 60 healthy controls were included. Subgroups (n=15) were defined on
      the basis of age (males) or menopausal status (females). Bone mineral density;
      serum parathyroid hormone (PTH), calcium (Ca), phosphorus (P), total alkaline
      phosphatase, and 25-hydroxy vitamin D levels; 24-hour urinary levels of Ca and P;
      and urinary telopeptide (NTX) were measured. Statistical comparisons were made
      between patient groups and the matched controls. RESULTS: Compared to controls,
      the average serum levels of PTH were lower and 24-hour urinary mean Ca levels and
      T scores were higher in chronic hepatitis B patients between 20 and 40 years of
      age. Men with chronic hepatitis B and aged 40 - 65 years had lower mean serum P
      concentrations. Postmenopausal women with chronic hepatitis B had significantly
      higher NTX levels. Men with chronic hepatitis C had significantly elevated levels
      of 24-hour mean urinary P levels. The serum 25 OH vitamin D levels were
      significantly higher in premenopausal women with chronic hepatitis C.
      Postmenopausal women with chronic hepatitis C had significantly lower serum P
      concentrations. Other parameters and T scores did not differ significantly
      between patient groups and matched controls. CONCLUSION: Our results suggest that
      chronic hepatitis B and C infections do not pose a risk for osteoporosis and low
      bone mineral density.

PMID- 17205404
TI  - Hepatitis B and C virus in West-Central Turkey: seroprevalence in healthy
      individuals admitted to a university hospital for routine health checks.
AB  - BACKGROUND/AIMS: The aim was to determine the seroprevalence rates for hepatitis
      B virus and hepatitis C virus and the frequency of hepatitis B core antibody
      seropositivity alone in residents of a city in Turkey. The subjects visited the
      Family Medicine Outpatient Clinics of a university hospital in Afyon for routine
      health checks between January 2002 and January 2004. METHODS: A single serum
      sample was collected from subjects examined. The sera were analyzed by ELISA for
      hepatitis B surface antigen, hepatitis B surface antibody, anti-HBcIgG and anti
      hepatitis C virus. Samples that were HBsAg-positive were also screened for
      hepatitis B early antigen and antibody. Subjects who were positive for anti
      HBcIgG alone were considered to have "isolated anti-HBcIgG positivity". RESULTS:
      1320 persons weere screened the rates of positivity for HBsAg, anti- HBs,
      isolated anti-HBcIgG, and anti-hepatitis C virus were 6.6%, 27.2%, 6.1% and 2.2%,
      respectively. Eight percent of the 87 HBsAg-positive individuals were HBeAg
      positive. Comparison of marker detection rates according to sex and age (younger
      than 50 years vs 50 years or older) revealed a significantly higher prevalence of
      HBsAg positivity in males than in females (p=0.02), and a significantly higher
      prevalence of anti-hepatitis C virus and anti-HBcIgG positivity in the older than
      in the younger group (p=0.001 and p=0.001, respectively). CONCLUSION: According
      to our results, the rates of hepatitis B virus and hepatitis C virus
      seropositivities in our region are similar to those reported in recent studies
      from other parts of Turkey. But these results cannot be extrapolated to all
      residents of the Afyon area because a random sampling method was not used for
      statistical analysis. However, they provide a good reference for future studies
      because of the large number of cases investigated.

PMID- 17205405
TI  - The results of surgical treatment for hepatic hydatid cysts in an endemic area.
AB  - BACKGROUND/AIMS: Hydatid cyst remains an important public health problem in
      endemic areas. METHODS: This study retrospectively reviewed medical records of 63
      patients treated for hepatic cyst hydatidosis in Frat University, Medical School,
      Department of General Surgery between January 1994 and December 2002. RESULTS:
      There were 96 cysts in total in 63 patients, with 67 (69%) of them located in the
      right lobe of the liver. Of 96 hepatic cysts, 41 (45%) were treated with partial
      cystectomy and drainage, 25 (26%) with partial cystectomy and capitonnage and 15
      (15%) with partial cystectomy and omentoplasty. Thirty-two patients (51%)
      received treatment with albendazole while 31 (49%) received no medical therapy.
      The postoperative complication rate was 19% and there was no significant
      difference in the early post-operative complications between surgical procedures
      (p>0.05). Cysts recurred in 6 patients (11%) and no correlation was found between
      recurrence of cysts and albendazole use, type of surgical procedure, number and
      size of the cysts, Gharbi classification as determined by ultrasound examination
      or the relation of the cyst with the biliary tract (p>0.05). CONCLUSION: It was
      concluded that there was no significant difference in the rates of complications
      and recurrences among different surgical procedures when performed with basic
      rules of the surgical principles.

PMID- 17205406
TI  - Changes in pulse oximetry levels and factors affecting oxygen saturation during
      routine upper gastrointestinal endoscopy with or without sedation.
AB  - BACKGROUND/AIMS: We aimed to investigate whether endoscopy or midazolam as
      premedication causes oxygen desaturation and to determine factors which may
      affect the occurrence of oxygen desaturation. METHODS: Totally 200 patients with
      various indications (103 men and 97 women), who presented to the Endoscopy Unit
      of Dicle University Hospital for upper gastrointestinal endoscopy examination,
      were included in the study. Anamnesis and anthropometric values of the patients
      were taken. Preoperative oxygen saturation, hemoglobin levels and heart rate per
      minute were recorded. Patients with initial oxygen saturation levels <90% were
      excluded. Patients were divided into two groups. The first group included 100
      patients who underwent endoscopic examination without sedation and the second
      group included 100 patients who underwent endoscopic examination with sedation
      [midazolam (2-5 mg)]. At the end of endoscopy, intravenous flumazenil (0.2 mg)
      was administered to the premedication patients. Patients were monitored for
      oxygen saturation and heart rate starting before the sedation and oropharynx
      anesthesia and lasting until 1 min after the end of the procedure. During the
      endoscopic examination, minimum oxygen saturation and maximum heart rate values
      were recorded. The duration of the oxygen saturation <90% was recorded throughout
      the procedure and the relation of this time with the total time of the endoscopic
      examination was evaluated. RESULTS: The mean age of the 200 patients included in
      the study was 45 and 44 years for Group 1 and Group 2, respectively. No
      differences were found between the two groups in terms of body mass index,
      smoking, hemoglobin and basal maximum pulse rate, duration of endoscopy, minimum
      basal oxygen saturation, duration of hypoxia and time to hypoxia. No relation was
      determined between oxygen desaturation and gender, duration of the endoscopy,
      basal pulse rate or hemoglobin level. It was found that smoking made significant
      contributions to the oxygen desaturation. CONCLUSION: Midazolam premedication for
      upper gastrointestinal system endoscopy is a reliable procedure and does not
      contribute an additional risk in individuals without serious comorbidities.
      Smoking habits should be taken into account in endoscopy patients.

PMID- 17205407
TI  - The effect of preoperative blood transfusion on morbidity and survival in
      colorectal malignancy.
AB  - BACKGROUND/AIMS: It is believed that blood transfusions adversely affect
      colorectal cancer surgery. However, intra- and postoperative blood transfusions
      represent urgent interventions, and immeasurable confounding factors may affect
      the shortand long-term outcome. Therefore, we compared colorectal cancer patients
      who had received preoperative blood transfusion with patients who did not receive
      transfusions with regard to postoperative complications and long-term outcome.
      METHODS: The records of 333 patients who were operated for colorectal malignancy
      between 1980 and 1995 were evaluated. RESULTS: Sixty-one patients (18.3%)
      received preoperative blood transfusions. Wound infection rate was higher (14.2%
      vs 1.9%) in the no-transfusion group. Disease-free survival was not different
      between the groups (p=0.134). Cumulative survival was adversely affected in the
      preoperative transfusion group (p=0.012). However, preoperative blood transfusion
      did not emerge to be an independent factor for wound infection or for death on
      follow-up when the confounding factors were corrected. CONCLUSION: Preoperative
      transfusion during surgery for colorectal malignancy does not result in an
      increase in postoperative complications, long-term failure or death rates.

PMID- 17205408
TI  - Comparison of virtual colonoscopy with conventional colonoscopy in detection of
      colorectal polyps.
AB  - BACKGROUND/AIMS: To determine the sensitivity and specificity of multidetector
      computed tomography-based virtual colonoscopy for colorectal polyp detection by
      using conventional colonoscopy as the reference standard. METHODS: 48 patients
      with high risk for colorectal cancer underwent virtual colonoscopy followed by
      conventional colonoscopy. Examination results were compared with conventional
      colonoscopy, which served as the gold standard. RESULTS: Virtual colonoscopy
      correctly depicted 19 of 22 polyps (sensitivity, 86%) that were detected in
      conventional colonoscopy. All 4 polyps that were greater than 10 mm in size
      (100%), 6 of 7 polyps 6-9 mm in size (85%), and 9 of 11 polyps 5 mm in size or
      smaller (81%) were correctly depicted with virtual colonoscopy. Virtual
      colonoscopy had an overall sensitivity of 86% and specificity of 98%. CONCLUSION:
      Multidetector computed tomography-based virtual colonoscopy has excellent
      sensitivity for the detection of clinically important colorectal polyps.

PMID- 17205409
TI  - Management of cervical esophageal strictures with self-expanding metalic stents.
AB  - Esophageal strictures due to malignant diseases are treated with self-expanding
      metalicic stents. However, experience is limited with these metalic stents in the
      cervical esophagus. Due to technical difficulties and procedure-related
      complications, the cervical esophagus has been assigned as a risky area for
      stenting procedures. Another encountered problem is patient discomfort after the
      procedure. In this case report, we present three patients with cervical
      esophageal strictures who were successfully treated with self-expandable metalic
      stents. Two of these patients had inoperable esophageal carcinoma and the third
      had benign stenosis due to radiotherapy of larynx carcinoma. The two patients
      with malignant disease survived four and six months, respectively, after the
      procedure. The last patient with benign disease is still alive and has been
      without dysphagia symptom for six months.

PMID- 17205410
TI  - Liver penetration of duodenal ulcer.
AB  - Liver penetration is a rare complication of peptic ulcer disease.
      Histopathological examination of endoscopic biopsy is essential for diagnosis as
      well as sonographic and computerized tomography imaging. Endoscopic examination
      could not exclude tumor without pathologic examination. Herein, we report a
      patient diagnosed as duodenal ulcer penetration into liver by endoscopic biopsy.

PMID- 17205411
TI  - An interesting coexistence: small bowel volvulus and small bowel diverticulosis.
AB  - Acquired (non-Meckel's) jejuno-ileal diverticular disease is uncommon, and most
      surgeons have limited, if any, experience with this condition. We present an
      interesting case with coexistence of small bowel diverticulum and small bowel
      volvulus with massive abdominal distension, in which the patient had a history of
      abdominal distension without abdominal pain over a five-year period. A brief
      discussion of the common clinical features is given and the principles of
      treatment of jejuno-ileal diverticular disease and small bowel volvulus are
      presented. A 29-year- old man with no history of laparotomy was admitted with
      abdominal distension and abdominal compartment syndrome symptoms. An emergency
      laparotomy revealed 180 degree clockwise volvulus of the multiple diverticula
      bearing terminal ileum. There was no diverticulum in other sites of the small
      intestine and colon. Additionally, there was neither adhesion nor any congenital
      anomalies at the other sites of the gastrointestinal system. The viability of the
      intestine was normal but the diameter of the ileum was extremely enlarged
      (approximately 20 cm). In addition, the bowel wall was also hypertrophied. The
      rotated and enormously enlarged diverticula-bearing small intestine was removed
      with cecum, and ileocolostomy was performed. The patient was discharged
      uneventfully from hospital on the eighth postoperative day. After the operation,
      all symptoms of the patient disappeared. Small bowel obstruction is a common
      cause of emergency surgical admission. Awareness of the fact that volvulus of the
      diverticula-bearing segment of the jejuno- ileum is a rare cause of small bowel
      obstruction may lead to earlier and prompt diagnosis and treatment.

PMID- 17205412
TI  - Mechanical bowel obstruction due to colonic hemangioma: report of a case.
AB  - Colon hemangiomas are rare benign vascular lesions which are usually seen in
      teenagers. The frequent presentation is repetitive painless rectal bleeding.
      Colonic hemangiomas are occasionally found in the rectosigmoid area. A 62-year
      old male patient was admitted to the hospital with the complaints of mechanical
      bowel obstruction. The radiological imaging techniques revealed a transverse
      colon tumor. Consequently, the patient was operated, and transverse colectomy and
      end-to-end anastomosis were performed. No postoperative complications occurred.
      The pathologic examination revealed cavernous hemangioma of the transverse colon.
      This report describes a very rare case of bowel obstruction due to colonic
      hemangioma.

PMID- 17205413
TI  - Diffuse cavernous hemangioma of the rectosigmoid colon with extraintestinal
      involvement.
AB  - Cavernous hemangioma of the colon is a rare cause of gastrointestinal bleeding.
      These lesions can be encountered as solitary, multiple, or part of a more complex
      syndrome with cutaneous manifestations. We herein describe a 26-year-old woman
      with cavernous hemangioma involving the rectosigmoid area. Additional hemangiomas
      were identified in the pelvic structures, spine, iliac bone and spleen. This
      multi-visceral involvement without cutaneous manifestations represents an
      intermediate variety between solitary hemangioma and well-defined syndromes with
      cutaneous and structural anomalies. The potential presence of extraintestinal
      hemangiomatosis should be considered and investigated in patients with cavernous
      hemangioma of the colon even without cutaneous manifestations or with a limited
      colonic involvement.

PMID- 17205414
TI  - Endoscopic submucosal resection of a rectal carcinoid tumor by cap aspiration -
      snare resection method.
AB  - We report a 55-year-old man with a white plaque-like lesion 4 mm in diameter
      located in the rectum on colonoscopic examination. Biopsy specimens showed
      carcinoid tumor. Endoscopic submucosal resection (ESMR) of the lesion was
      successfully performed by using cap aspiration-snare resection method.

PMID- 17205415
TI  - Solid pseudopapillary tumor of the pancreas: a case report.
AB  - A 29-year-old woman presented with an abdominal mass existing for 10 years and
      abdominal pain for one year. Physical examination revealed an abdominal mass
      about 10 cm in diameter between the epigastrium and right upper quadrant.
      Abdominal ultrasonography and multi-slice computerized tomography showed a well
      demarcated solid mass containing cystic and calcified areas (97-80 mm in
      diameter) located on the head and uncinate process of the pancreas. Percutaneous
      ultrasonographyguided tru-cut biopsy was performed and the pathologic diagnosis
      of biopsy material was solid pseudopapillary tumor of the pancreas. The patient
      then underwent surgery and exploration revealed an encapsulated mass of 10 cm in
      diameter that was retracting the portal vein and was adherent to mesentery of the
      transverse colon. Pancreaticoduodenectomy was performed preserving the pylorus.
      Histopathologic diagnosis of the mass supported the tru-cut biopsy findings. At
      12th months of follow-up, physical, laboratory and radiological examinations were
      all normal. Although solid pseudopapillary tumor is a rarely seen low-grade
      malignant tumor, it is important to differentiate it from other pancreatic tumors
      because of its benign course.

PMID- 17205416
TI  - Portal venous aneurysm and liver cirrhosis.

PMID- 17205419
TI  - Myometrial progesterone responsiveness.
AB  - Progesterone actions in human pregnancy are controlled by the extent of
      myometrial progesterone responsiveness. Current progress in unraveling the
      biochemistry for myometrial progesterone responsiveness at the genomic and
      nongenomic levels have lead to novel hypotheses regarding the role of these
      pathways in the hormonal control of human pregnancy and parturition. For the
      genomic pathway, progesterone interacts with the type-B nuclear progesterone
      receptor (nPR-B), which decreases expression of contraction-associated genes. For
      the nongenomic pathway, progesterone interacts with membrane-associated PRs
      (mPRs) to modulate directly intracellular Ca2+ and cyclic adenosine monophosphate
      (cAMP) levels. During most of human pregnancy the genomic and nongenomic pathway
      cooperate to maintain myometrial relaxation. However, at parturition the relaxing
      actions of progesterone are nullified by changes in myometrial progesterone
      responsiveness. This occurs by (1) increased expression of the nPR variants
      (e.g., PR-A and/or PR-C) and changes in nPR coregulator levels that together
      repress the transcriptional activity of PR-B; and (2) increased expression of
      specific mPRs, especially mPRss, which augments contractility by decreasing
      intracellular cAMP. Functional progesterone withdrawal may be induced by locally
      produced prostaglandins that alter myometrial nPR expression. This may be an
      important physiological link between the control of parturition and the
      immune/inflammatory process.

PMID- 17205420
TI  - The human fetal adrenal gland, corticotropin-releasing hormone, and parturition.
AB  - Labor initiation is a complex process that remains to be fully elucidated. An
      area of active research involves the study of the different mechanisms that may
      lead to successful signaling for parturition. This review focuses on the fetal
      derived signals that lead to the initiation of labor. These signals may also play
      a role in preterm labor when activated prematurely. Studying these signals may
      prove important in the prediction, diagnosis, and possible intervention in
      preterm labor.

PMID- 17205421
TI  - The role of inflammation and infection in preterm birth.
AB  - Inflammation has been implicated in the mechanisms responsible for preterm and
      term parturition, as well as fetal injury. Out of all of the suspected causes of
      preterm labor and delivery, infection and/or inflammation is the only
      pathological process for which both a firm causal link with preterm birth has
      been established and a molecular pathophysiology defined. Inflammation has also
      been implicated in the mechanism of spontaneous parturition at term. Most cases
      of histopathological inflammation and histological chorioamnionitis, both in
      preterm and term labor, are sub-clinical in nature. The isolation of bacteria in
      the amniotic fluid, known as microbial invasion of the amniotic cavity, is a
      pathological finding; the frequency of which is dependent upon the clinical
      presentation and gestational age. This article reviews the role of inflammation
      in preterm and term parturition.

PMID- 17205422
TI  - Genetic influences on preterm birth.
AB  - The high prevalence, increasing frequency, and adverse outcomes for mothers and
      infants of preterm birth have led to heightened awareness of this public health
      concern. The causes of preterm birth are likely to be multifactorial, with
      genetic, infectious, nutritional, behavioral, and other environmental
      contributors. Because of important differences in the physiology of human
      pregnancy and that of nonprimate mammals, extrapolation of mechanisms from animal
      model systems to humans has had limited impact on the understanding of human
      prematurity. This review summarizes work from many groups that implicates
      important genetic contributions to human preterm birth. These efforts use
      epidemiological, classical genetic, and more recently, genomic science approaches
      to determine pregnancies at risk for preterm delivery and to facilitate an
      understanding of the substantial racial disparity in preterm birth. Data
      revealing racial and familial predispositions to prematurity, along with genetic
      polymorphisms conferring increased preterm birth, promise new insights into the
      understanding and treatment of this critical problem.

PMID- 17205423
TI  - Regulation of oxytocin receptors and oxytocin receptor signaling.
AB  - The oxytocin (OT) -oxytocin receptor (OTR) system plays a key role in many
      aspects of mammalian reproduction as well as several other physiological
      processes such as bond pairing and cardiovascular homeostasis. To manifest these
      diverse physiological roles, the transcription and expression of the OTR is
      tightly regulated within reproductive, cardiovascular, and neuronal tissues. The
      expression of the OTR within the mammalian uterus is regulated during gestation
      with a peak at the day of delivery. The control of this dramatic increase in
      expression is mediated in rodent species by a combination of stretch, classical
      steroid hormone stimulation, and repression. In the human uterus events are less
      clear, although a prominent role for inflammatory-related rapid-response genes
      and novel transcription factors such as hMafF (human homologue of chicken
      musculoaponeurotic fibrosarcoma oncogene family protein F) have been put forward.
      In the uterus the potent uterotonic actions of OT are mediated by the OTR through
      G-protein activation to stimulate phospholipase C activity. The activated OTR
      increases contraction frequency and increases force by sensitizing the
      contractile apparatus of the myocytes to calcium. This review summarizes the
      current knowledge of the complex regulation of OTR transcription in the
      myometrium and the intracellular signaling mechanisms through which OT mediates
      its potent stimulatory effects.

PMID- 17205424
TI  - Prostaglandin F2alpha and its receptor as activators of human decidua.
AB  - Prostaglandins produced by the intrauterine tissues of both mother and fetus
      (myometrium, decidua, placenta, chorion, and amnion) are involved with all of the
      physiologies of parturition (membrane rupture, cervical dilatation, myometrial
      contractility, placental separation, and uterine involution). For parturition to
      occur, however, the intrauterine tissues need to first be activated to prepare
      for the work of labor, then stimulated to initiate labor. Prostaglandins normally
      are considered to be stimulators of the physiologies of labor. This review
      presents evidence that one prostaglandin, PGF2alpha, and its receptor, FP, are
      also activators, especially of the decidua. Stimulated by cytokines, the decidual
      synthesis of PGF2alpha and the expression of FP lead to increased matrix
      metalloproteinase activity, further enhancement of cytokine activity, increased
      decidual oxytocin and oxytocin receptor expression, decreased progesterone
      responsiveness, and possibly, enhanced expression of vascular endothelial growth
      factor. These collective actions prepare the decidua for its role in parturition.

PMID- 17205425
TI  - Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and
      current concepts.
AB  - The cervix serves as a protective barrier from invading microorganisms and as a
      structural barrier to delivery of the fetus. Among all biological processes, the
      phenomenal connective tissue remodeling that occurs in the cervix during and
      after parturition is unparalleled in scope and magnitude. The process of
      connective tissue remodeling in the cervix during pregnancy occurs in four
      stages: softening, ripening, dilation, and repair. Although overlapping in time,
      each stage is uniquely regulated. Results from studies using serial measurements
      of cervical length indicate that cervical ripening precedes myometrial
      contractions of labor by several weeks, suggesting that parturition in women is a
      process of long duration and that uterine contractions of labor are late events
      in the parturition process. A clear understanding of the biologic mechanisms that
      regulate cervical remodeling during pregnancy is needed to influence the preterm
      birth rate and to develop strategies to prevent preterm dilation of the cervix.

PMID- 17205427
TI  - [Methylphenidate double-blind trial: indication and performing].
AB  - Hyperkinetic disorders or attention-deficit/hyperactivity disorders (ADHD) are
      among the psychiatric diagnoses most often encountered in children and
      adolescents. Symptoms include inattention, hyperactivity and impulsivity. Within
      the multi-modal treatment system, the therapy with psychostimulants (e. g.
      methylphenidate) proved to be an effective in patients with ADHD. A double-blind
      trial is indicated in cases of unclear efficacy of methylphenidate at initial
      application or if psychostimulants have regularly been applied for more than one
      year with an leave-out trial delivering unequivocal results. Further it is
      helpful in verifying potential undesirable side effects and improving patients'
      compliance.

PMID- 17205428
TI  - [Early identification of developmental language disorders--predictive value of
      the German version of the CDI--infant form (ELFRA-1)].
AB  - BACKGROUND: Early identification of developmental language disorders is a
      precondition for early intervention and therefore of high clinical relevance. The
      ELFRA-1 was constructed to identify children at risk for language disorders in
      the context of the routine examination of children at the age of 12 months. The
      aim of the study was to determine the predictive validity of this screening tool.
      SUBJECTS AND METHOD: 121 parents completed the questionnaire for their 12 months
      old children. One year later the language development was assessed by means of
      the ELFRA-2, the German version of the CDI for two year old children. RESULTS:
      63% of the children were correctly classified. The sensitivity amounted to 52%
      and the specificity to 65%. The RATZ-index (relative improvement of the hit rate
      in comparison to the random hit rate) was 23%, which has to be considered as
      unsatisfying. Improvement of language abilities were less likely in boys compared
      to girls and in cases of low educational background of the mother. CONCLUSIONS:
      The prognostic validity of the ELFRA-1 is insufficient and too low to identify
      children at risk for later language impairment. The screening overlooked too many
      late talkers and classified too many normally developed children as language
      impaired. The ELFRA-1 can not be recommended as a useful method for the early
      identification of language impaired children at the age of 12 months.

PMID- 17205429
TI  - [Measurement of activities of daily living in children--standardisation of a
      screening questionnaire].
AB  - BACKGROUND: Especially at preschool age, but also at school age, it is a major
      issue to what extent developmental problems are relevant for activities of daily
      living. This should be important for the prescription of therapeutic
      interventions. Previous instruments require training and/or they are time
      consuming (e. g. interviews, direct observation and testing) or they are not
      suitable for the target group. The objective of the presented screening
      questionnaire for parents and professionals is a quick and standardised
      instrument for the status of everyday activities, particular in children with
      physical and mental delays or handicaps. The study examines the interrater and
      the retest reliability. PATIENTS AND METHODS: A questionnaire (M-ADL) with the
      subscales eating and drinking, hand skill in everyday life, toiletting and
      mobility was tested. The ratings were carried out on two levels: first, a global
      rating from 0 to 10 had to be given on each subscale. Secondly, a rating based on
      a defined scale had to be given. The average time for evaluation is about 5
      minutes. We examined 28 children with cerebral palsy for the test-retest
      reliability, and 48 children for the interrater reliability. The children had all
      types of cerebral palsy and all degrees of severity rated according to the Gross
      Motor Function Classification Scale cerebral palsy. RESULTS: The M-ADL total
      scores showed an excellent interrater reliability (r=0.84 to r=0.89) and test
      retest-reliability (r=0.91 to r=0.97). Each subscale had a good reliability (at
      least r=0.73). CONCLUSION: The M-ADL is a reliable, economic measure for
      activities of daily living for children with physical and mental delays or
      handicaps. The instrument may serve as a tool for quick information on the level
      of activities according to the International Classification of Functioning (ICF).

PMID- 17205430
TI  - [Preparation of a compatibility chart for intravenous drug therapy in neonatal
      and pediatric intensive care units].
AB  - BACKGROUND: Modern neonatal and pediatric intensive care includes a sophisticated
      pharmacotherapy with numerous drugs, mainly administered intravenously. Often,
      despite the use of multi-lumen central venous lines, more peripheral venous
      accesses are required. To reduce the necessity of numerous venous lines on one
      hand and on the other hand to avoid complications from incompatibilities of the
      administered drugs, we compiled a compatibility chart, encompassing more
      substances than covered in previously available charts. METHODS: Information on
      compatibility of commonly prescribed drugs was collected by analysis of
      manufacturers' information, medical and pharmaceutical handbooks, and a
      literature research. RESULTS: Available data on compatibility of 78 drugs were
      displayed in a two-dimensional chart. Beside the pH of each drug, compatibility
      of drug combinations was encoded for simultaneous infusion. Special emphasis was
      on security of the therapy. CONCLUSION: The compatibility chart gives quick
      reference for Data on compatibility of intravenously administered drugs in
      neonatal and pediatric intensive care.

PMID- 17205431
TI  - Acute hepatitis delta virus infection in Italy: incidence and risk factors after
      the introduction of the universal anti-hepatitis B vaccination campaign.
AB  - BACKGROUND: Updates on the incidence of and risk factors for acute hepatitis
      delta virus infection in Italy, as well as in other countries, are lacking, and
      the impact of the mandatory anti-hepatitis B vaccination has not been evaluated.
      METHODS: We performed a case-control study within a population-based surveillance
      for acute viral hepatitis. RESULTS: During 1993-2004, 344 cases of acute
      hepatitis delta virus infection were reported. After a peak in 1993 (2.8 cases
      per 1 million population), the incidence decreased from 1.7 to 0.5 cases per 1
      million population. Coinfections were prevalent. The decrease in incidence
      particularly affected young adults, and it paralleled the decrease in incidence
      of acute hepatitis B. In 1993, being an injection drug user (adjusted odds ratio
      [OR(adj)], 67.9; 95% confidence interval [CI], 18.1-254.5) or being a member of a
      household with a carrier of hepatitis B surface antigen (OR(adj,) 14.8; 95% CI,
      3.0-72.9) were the only independent predictors of infection. During 1994-2004,
      being an injection drug user (OR(adj), 36.8; 95% CI, 20.7-65.4), cohabitation
      with an injection drug user (OR(adj), 4.2, 95% CI, 1.7-12.3), hospitalization
      (OR(adj), 3.5; 95% CI, 1.9-6.6), receipt of dental therapy (OR(adj), 2.3; 95% CI,
      1.4-3.6), promiscuous sexual activity (OR(adj), 2.2; 95% CI, 1.4-3.6), and
      receipt of beauty treatment (OR(adj), 2.0; 95% CI, 1.3-3.2) were independently
      associated with infection. CONCLUSIONS: Incidence of acute hepatitis delta
      infection is markedly decreasing in Italy. Undergoing invasive medical
      procedures, engaging in promiscuous sexual activity, and receiving beauty
      treatments are emerging, in addition to injection drug use, as important risk
      factors for infection. Further efforts are needed to increase vaccine coverage in
      high-risk groups and to implement the safety of invasive procedures performed
      both inside and outside health care facilities.

PMID- 17205432
TI  - Selective defect in plasmacyoid dendritic cell function in a patient with AIDS
      associated atypical genital herpes simplex vegetans treated with imiquimod.
AB  - We report a case of acquired immunodeficiency syndrome (AIDS)-associated,
      acyclovir-refractory genital herpes infection treated with topical
      imidazoquinoline therapy. The patient's plasmacytoid dendritic cells made a
      robust interferon- alpha response following in vitro stimulation with
      imidazoquinoline but not with herpes simplex virus. We hypothesize that disease
      resulting from defective herpes simplex virus-stimulated interferon- alpha may be
      overcome by stimulating intact alternative pathways.

PMID- 17205433
TI  - Multiple organ failure during primary HIV infection.
AB  - The appearance of primary HIV infection ranges from an asymptomatic presentation
      to a symptomatic illness resembling infectious mononucleosis. Severe unusual
      presentations include acute myopericarditis, renal failure, and opportunistic
      infections such as esophageal candidiasis, cytomegalovirus infection, and
      Pneumocystis jirovecii pneumonia. We report a case of multiple organ failure
      during primary HIV infection.

PMID- 17205434
TI  - Nursing and community rates of Mycobacterium tuberculosis infection among
      students in Harare, Zimbabwe.
AB  - BACKGROUND: African hospitals have experienced major increases in admissions for
      tuberculosis, but they are ill-equipped to prevent institutional transmission. We
      compared institutional rates and community rates of tuberculin skin test (TST)
      conversion in Harare, Zimbabwe. METHODS: We conducted a cohort study of TST
      conversion 6, 12, and 18 months into training among 159 nursing and 195
      polytechnic school students in Harare. Students had negative TST results
      (induration diameter, < or =9 mm) with 2-step testing at the start of training.
      RESULTS: Nursing students experienced 19.3 TST conversions (increase in
      induration diameter, > or =10 mm) per 100 person-years (95% confidence interval
      [CI], 14.2-26.2 conversions per 100 person-years), and polytechnic school
      students experienced 6.0 (95% CI, 3.5-10.4) conversions per 100 person-years. The
      rate of difference was 13.2 conversions (95% CI, 6.5-20.0) per 100 person-years.
      With a more stringent definition of conversion (increase in the induration
      diameter of > or =10 mm to at least 15 mm), which is likely to increase
      specificity but decrease sensitivity, conversion rates were 12.5 and 2.8
      conversions per 100 person-years in nursing and polytechnic school students,
      respectively (rate difference, 9.7 conversions per 100 person-years; 95% CI, 4.5
      14.8 conversions per 100 person-years). Nursing students reportedly nursed 20,868
      inpatients with tuberculosis during 315 person-years of training. CONCLUSIONS:
      Both groups had high TST conversion rates, but the extremely high rates among
      nursing students imply high occupational exposure to Mycobacterium tuberculosis.
      Intense exposure to inpatients with tuberculosis was reported during training.
      Better prevention, surveillance, and management of institutional M. tuberculosis
      transmission need to be supported as part of the international response to the
      severe human immunodeficiency virus infection epidemic and health care worker
      crisis in Africa.

PMID- 17205435
TI  - Tuberculosis risks for health care workers in Africa.

PMID- 17205436
TI  - Case-control study of shigellosis in San Francisco: the role of sexual
      transmission and HIV infection.
AB  - BACKGROUND: Shigella species infect approximately 450,000 persons annually in the
      United States. Person-to-person transmission of Shigella species, which have a
      low infectious dose, occurs frequently, particularly in areas with poor
      sanitation and hygiene. Sexual transmission of Shigella species among men who
      have sex with men (MSM) has been inferred from outbreaks of shigellosis among
      that population, and limited studies have suggested the importance of human
      immunodeficiency virus (HIV) infection as a risk factor for shigellosis. No
      population-based study of sporadic shigellosis has evaluated the role of sexual
      practices (especially among MSM) and HIV infection along with other established
      risk factors for shigellosis. METHODS: We conducted a population-based case
      control study of shigellosis in adults in San Francisco, California, during the
      period 1998-1999. Cases of Shigella infection were identified through laboratory
      based active surveillance conducted by the California Emerging Infections
      Program. Seventy-six case patients were matched by sex with 146 control subjects.
      Exposure data were collected on established risk factors, sexual practices, and
      HIV infection status. Bivariable and multivariable analyses were conducted.
      Population-attributable fractions were calculated. RESULTS: From the
      multivariable analysis, for men, shigellosis was associated with MSM (odds ratio
      [OR], 8.24; 95% confidence interval [CI], 2.70-25.2), HIV infection (OR, 8.17;
      95% CI, 2.71-24.6), direct oral-anal contact (OR, 7.50; 95% CI, 1.74-32.3), and
      foreign travel (OR, 20.0; 95% CI, 5.26-76.3), with population-attributable
      fractions of 0.72, 0.42, 0.31, and 0.18, respectively. For women, shigellosis was
      associated only with foreign travel (OR, 21.0; 95% CI, 2.52-899), with a
      population-attributable fraction of 0.37. CONCLUSIONS: Among MSM, shigellosis is
      predominantly a sexually transmitted disease, with direct oral-anal contact
      conferring the highest risk and HIV infection likely contributing to increased
      host susceptibility.

PMID- 17205437
TI  - Another perfect storm: Shigella, men who have sex with men, and HIV.

PMID- 17205438
TI  - Traveler's diarrhea in Thailand: randomized, double-blind trial comparing single
      dose and 3-day azithromycin-based regimens with a 3-day levofloxacin regimen.
AB  - BACKGROUND: Traveler's diarrhea in Thailand is frequently caused by Campylobacter
      jejuni. Rates of fluoroquinolone (FQ) resistance in Campylobacter organisms have
      exceeded 85% in recent years, and reduced fluoroquinolone efficacy has been
      observed. METHODS: Azithromycin regimens were evaluated in a randomized, double
      blind trial of azithromycin, given as a single 1-g dose or a 3-day regimen (500
      mg daily), versus a 3-day regimen of levofloxacin (500 mg daily) in military
      field clinics in Thailand. Outcomes included clinical end points (time to the
      last unformed stool [TLUS] and cure rates) and microbiological end points
      (pathogen eradication). RESULTS: A total of 156 patients with acute diarrhea were
      enrolled in the trial. Campylobacter organisms predominated (in 64% of patients),
      with levofloxacin resistance noted in 50% of Campylobacter organisms and with no
      azithromycin resistance noted. The cure rate at 72 h after treatment initiation
      was highest (96%) with single-dose azithromycin, compared with the cure rates of
      85% noted with 3-day azithromycin and 71% noted with levofloxacin (P=.002).
      Single-dose azithromycin was also associated with the shortest median TLUS (35 h;
      P=.03, by log-rank test). Levofloxacin's efficacy was inferior to azithromycin's
      efficacy, except in patients with no pathogen identified during the first 24 h of
      treatment or in patients with levofloxacin-susceptible Campylobacter isolates, in
      whom it appeared to be equal to azithromycin. The rate of microbiological
      eradication was significantly better with azithromycin-based regimens (96%-100%),
      compared with levofloxacin (38%) (P=.001); however, this finding was poorly
      correlated with clinical outcome. A higher rate of posttreatment nausea in the 30
      min after receipt of the first dose (14% vs. <6%; P=.06) was observed as a mild,
      self-limited complaint associated with single-dose azithromycin. CONCLUSIONS:
      Single-dose azithromycin is recommended for empirical therapy of traveler's
      diarrhea acquired in Thailand and is a reasonable first-line option for empirical
      management in general.

PMID- 17205439
TI  - Azithromycin for the self-treatment of traveler's diarrhea.

PMID- 17205440
TI  - Treatment of Bolivian mucosal leishmaniasis with miltefosine.
AB  - BACKGROUND: Although mucosal leishmaniasis is a prominent disease, it has been
      studied only to a limited extent. It is classically treated with parenteral
      antimony or, as a last resort, amphotericin B. METHODS: We treated Bolivian
      mucosal leishmaniasis due to Leishmania braziliensis with the oral agent
      miltefosine, 2.5 mg/kg/day for 28 days, and followed-up for 12 months. RESULTS:
      Seventy-two patients were evaluable. The cure rate for the 36 patients who had
      "mild" disease (i.e., affecting nasal skin and nasal mucosa) was 83%. The cure
      rate for the 36 patients who had more extensive disease (involving the palate,
      pharynx, and larynx) was 58%. Patients refused to be randomized to parenteral
      agents, but the cure rate for an almost contemporary group who was receiving
      amphotericin B (45 mg/kg over 90 days) was 7 (50%) of 14. CONCLUSIONS: In this
      unrandomized trial, oral miltefosine was at least as effective as heroic doses of
      parenteral amphotericin B. The cure rate for miltefosine was approximately
      equivalent to historical cure rates using parenteral pentavalent antimony for
      mild and extensive disease in neighboring Peru. Although gastrointestinal side
      reactions do occur with miltefosine, its toxicity profile is superior to that of
      antimony and far superior to that of amphotericin B--in part because of the
      inherent attractiveness of oral versus parenteral agents. Our results suggest
      that miltefosine should be the treatment of choice for mucosal disease in North
      and South America.

PMID- 17205441
TI  - Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical
      implications of an extended-infusion dosing strategy.
AB  - BACKGROUND: Piperacillin-tazobactam is frequently used to treat Pseudomonas
      aeruginosa infections in critically ill patients. In an effort to improve
      clinical outcomes, an extended-infusion dosing scheme for piperacillin-tazobactam
      therapy was devised using a Monte Carlo simulation and was adopted into clinical
      practice at Albany Medical Center (Albany, New York). This study evaluates the
      clinical implications of extended infusion of piperacillin-tazobactam therapy for
      critically ill patients with P. aeruginosa infection. METHODS: We performed a
      cohort study of patients who received piperacillin-tazobactam therapy for a P.
      aeruginosa infection that was susceptible to piperacillin-tazobactam during the
      period January 2000-June 2004. Prior to February 2002, all patients received
      intermittent infusions of piperacillin-tazobactam (3.375 g intravenously for 30
      min every 4 or 6 h); after this time, all patients received extended infusions of
      piperacillin-tazobactam (3.375 g intravenously for 4 h every 8 h). Data on
      demographic characteristics, disease severity, and microbiology were collected,
      and outcomes were compared between groups. RESULTS: A total of 194 patients
      comprised the 2 study groups: 102 patients received extended infusions of
      piperacillin-tazobactam, and 92 patients received intermittent infusions of
      piperacillin-tazobactam. No differences in baseline clinical characteristics were
      noted between the 2 groups. Among patients with Acute Physiological and Chronic
      Health Evaluation-II scores > or =17, 14-day mortality rate was significantly
      lower among patients who received extended-infusion therapy than among patients
      who received intermittent-infusion therapy (12.2% vs. 31.6%, respectively;
      P=.04), and median duration of hospital stay after collection of samples for
      culture was significantly shorter for patients who received extended-infusion
      therapy than for patients who received intermittent-infusion therapy (21 days vs.
      38 days; P=.02).Conclusions. These results indicate that extended-infusion
      piperacillin-tazobactam therapy is a suitable alternative to intermittent
      infusion piperacillin-tazobactam therapy, and they strongly suggest that improved
      outcomes may be realized by administering extended-infusion piperacillin
      tazobactam therapy to critically ill patients with P. aeruginosa infection.

PMID- 17205442
TI  - Early surgery in patients with infective endocarditis: a propensity score
      analysis.
AB  - BACKGROUND: An accurate assessment of the predictors of long-term mortality in
      patients with infective endocarditis is not possible using retrospective data
      because of inherent treatment biases and predictable imbalances in the
      distribution of prognostic factors. Largely because of these limitations, the
      role of surgery in long-term survival has not been adequately studied. METHODS:
      Data were collected prospectively from 426 patients with infective endocarditis.
      Variables associated with surgery in patients who did not have intracardiac
      devices who had left-side-associated valvular infections were determined using
      multivariable analysis. Propensity scores were then assigned to each patient
      based on the likelihood of undergoing surgery. Using individual propensity
      scores, 51 patients who received medical and surgical treatment were matched with
      51 patients who received medical treatment only. RESULTS: The following factors
      were statistically associated with surgical therapy: age, transfer from an
      outside hospital, evidence of infective endocarditis on physical examination, the
      presence of infection with staphylococci, congestive heart failure, intracardiac
      abscess, and undergoing hemodialysis without a chronic catheter. After adjusting
      for surgical selection bias by propensity score matching, regression analysis of
      the matched cohorts revealed that surgery was associated with decreased mortality
      (hazard ratio, 0.27; 95% confidence interval, 0.13-0.55). A history of diabetes
      mellitus (hazard ratio, 4.81; 95% confidence interval, 2.41-9.62), the presence
      of chronic intravenous catheters at the beginning of the episode (hazard ratio,
      2.65; 95% confidence interval, 1.31-5.33), and paravalvular complications (hazard
      ratio, 2.16; 95% confidence interval, 1.06-4.44) were independently associated
      with increased mortality. CONCLUSIONS: Differences between clinical
      characteristics of patients with infective endocarditis who receive medical
      therapy versus patients who receive surgical and medical therapy are paramount.
      After controlling for inherent treatment selection bias and imbalances in
      prognostic factors using propensity score methodology, risk factors associated
      with increased long-term mortality included diabetes mellitus, the presence of a
      chronic catheter at the onset of infection, and paravalvular complications. In
      contrast, surgical therapy was associated with a significant long-term survival
      benefit.

PMID- 17205443
TI  - Imaging findings in acute invasive pulmonary aspergillosis: clinical significance
      of the halo sign.
AB  - BACKGROUND: Computed tomography (CT) of the chest may be used to identify the
      halo sign, a macronodule surrounded by a perimeter of ground-glass opacity, which
      is an early sign of invasive pulmonary aspergillosis (IPA). This study analyzed
      chest CT findings at presentation from a large series of patients with IPA, to
      assess the prevalence of these imaging findings and to evaluate the clinical
      utility of the halo sign for early identification of this potentially life
      threatening infection. METHODS: Baseline chest CT imaging findings from 235
      patients with IPA who participated in a previously published study were
      systematically analyzed. To evaluate the clinical utility of the halo sign for
      the early identification and treatment of IPA, we compared response to treatment
      and survival after 12 weeks of treatment in 143 patients who presented with a
      halo sign and in 79 patients with other imaging findings. RESULTS: At
      presentation, most patients (94%) had > or =1 macronodules, and many (61%) also
      had halo signs. Other imaging findings at presentation, including consolidations
      (30%), infarct-shaped nodules (27%), cavitary lesions (20%), and air-crescent
      signs (10%), were less common. Patients presenting with a halo sign had
      significantly better responses to treatment (52% vs. 29%; P<.001) and greater
      survival to 84 days (71% vs. 53%; P<.01) than did patients who presented with
      other imaging findings. CONCLUSIONS: Most patients presented with a halo sign
      and/or a macronodule in this large imaging study of IPA. Initiation of antifungal
      treatment on the basis of the identification of a halo sign by chest CT is
      associated with a significantly better response to treatment and improved
      survival.

PMID- 17205444
TI  - Medical imaging and timely diagnosis of invasive pulmonary aspergillosis.

PMID- 17205445
TI  - Direct E-test (AB Biodisk) of respiratory samples improves antimicrobial use in
      ventilator-associated pneumonia.
AB  - BACKGROUND: Ventilator-associated pneumonia is the most frequently observed
      nosocomial infection in intensive care units, and it is associated with high
      morbidity and mortality. Early microbiological diagnosis and the initial
      administration of appropriate antimicrobial therapy are associated with decreased
      mortality and potentially reduced costs. Our study evaluates the clinical and
      financial impact of performing rapid antimicrobial susceptibility tests directly
      on samples obtained from the lower respiratory tract. METHODS: A prospective,
      randomized study was performed over a 2-year period. Patients who had a lower
      respiratory tract infection that was acquired during mechanical ventilation and
      for whom samples obtained from the respiratory tract were sent for culture were
      randomized to 1 of 2 groups. Samples were cultured for the control group, and
      results were reported using standard procedures. Samples were also cultured for
      the test subject group using standard procedures, but in addition, a rapid
      antibiogram was immediately performed by placing E-test antibiotic strips (AB
      Biodisk) directly on respiratory tract samples. Patients in the E-test group
      received a preliminary laboratory report when it became available. The 2 patient
      groups were compared according to the following variables: type and severity of
      underlying conditions, total days of antimicrobial use, number of defined daily
      doses, cost of acquisition of the antimicrobial agent per episode, days of fever,
      days receiving mechanical ventilation, days in the intensive care unit, incidence
      of Clostridium difficile-associated diarrhea, and mortality. RESULTS: Reporting a
      rapid E-test was associated with fewer days of fever, fewer days of antibiotic
      administration until resolution of the episode of ventilator-associated
      pneumonia, decreased antibiotic consumption, less C. difficile-associated
      diarrhea, lower costs of antimicrobial agents, and fewer days receiving
      mechanical ventilation. CONCLUSIONS: A rapid E-test of respiratory tract samples
      improves antimicrobial use in cases of ventilator-associated pneumonia.

PMID- 17205446
TI  - Moving towards real-time antimicrobial management of ventilator-associated
      pneumonia.

PMID- 17205447
TI  - Scrub typhus serologic testing with the indirect immunofluorescence method as a
      diagnostic gold standard: a lack of consensus leads to a lot of confusion.
AB  - A review was performed to determine the evidence base for scrub typhus indirect
      immunofluorescence assay (IFA) methodologies and the criteria for positive
      results. This review included a total of 109 publications, which comprised 123
      eligible studies for analysis (14 publications included 2 substudies). There was
      considerable underreporting of the IFA methodology and seropositivity criteria
      used, with most studies using a defined cutoff titer rather than an increase in
      the titer in paired samples. The choice of positivity cutoff titer varied by
      country and purpose of the IFA test. This variation limits the comparability of
      seroprevalence rates between studies and, more seriously, raises questions about
      the appropriateness of the cutoffs for positive IFA results chosen for diagnosis
      of acute scrub typhus infection. We suggest that the diagnosis of scrub typhus
      using IFA should be based on a > or =4-fold increase in the titer in paired serum
      samples and should only be based on a single sample titer when there is an
      adequate local evidence base.

PMID- 17205448
TI  - Prevention and early treatment of invasive fungal infection in patients with
      cancer and neutropenia and in stem cell transplant recipients in the era of newer
      broad-spectrum antifungal agents and diagnostic adjuncts.
AB  - Invasive fungal infection (IFI) is a leading cause of infection-related mortality
      among patients with cancer and prolonged neutropenia and among allogeneic
      hematopoietic stem cell transplant recipients with graft-versus-host disease.
      Invasive candidiasis was the principal IFI in the period predating fluconazole
      prophylaxis, whereas today, invasive aspergillosis and other mold infections
      cause the majority of deaths from fungal infection in this patient population.
      The changing epidemiology of IFI, in addition to advances made in antifungal
      therapeutics and early diagnosis of IFI, warrant a reevaluation of earlier
      strategies aimed at prevention and early treatment of IFI that were developed
      several years ago. Here, we propose that persistent neutropenic fever is
      nonspecific for an IFI and should not be used as the sole criterion for empirical
      modification in the antifungal regimen in a patient receiving mold-active
      prophylaxis. We explore the potential benefits and gaps in knowledge associated
      with employing chest CT scans and laboratory markers as diagnostic adjuncts for
      IFI. Finally, we discuss the implications of newer antifungal agents and
      diagnostic adjuncts in the design of future clinical trials to evaluate
      prophylaxis and early prevention strategies.

PMID- 17205449
TI  - Heterosexual transmission of community-associated methicillin-resistant
      Staphylococcus aureus.
AB  - Heterosexual transmission of community-associated methicillin-resistant
      Staphylococcus aureus has not been documented. As part of a survey conducted in
      northern Manhattan, we encountered 3 households in which heterosexual
      transmission was responsible for new community-associated methicillin-resistant
      S. aureus infection. The vaginal and inguinal isolates obtained from the sexual
      partners were USA 300. This report documents an important and previously
      unrecognized means of community-associated methicillin-resistant S. aureus
      colonization and transmission for these potentially invasive strains.

PMID- 17205450
TI  - Fatal pneumonia among metalworkers due to inhalation exposure to Bacillus cereus
      Containing Bacillus anthracis toxin genes.
AB  - Bacillus cereus pneumonia is unusual in nonimmunocompromised hosts. We describe
      fatal cases in 2 metalworkers and the associated investigation. Anthrax toxin
      genes were identified in B. cereus isolates from both patients using polymerase
      chain reaction. Finding anthrax toxin genes in non-Bacillus anthracis isolates
      has, to our knowledge, only been reported once previously.

PMID- 17205451
TI  - Man with a right thigh mass.

PMID- 17205452
TI  - Rapid detection and identification of bacterial pathogens using novel molecular
      technologies: infection control and beyond.
AB  - The rapid detection and reporting of antimicrobial-resistant pathogens, such as
      methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci,
      and multidrug-resistant Mycobacterium tuberculosis, is a challenge for the
      clinical microbiology laboratory. Molecular-based diagnostic tests can provide
      data on the presence of methicillin-resistant S. aureus in the nares in
      approximately 1 h, whereas testing for the vanA and vanB resistance genes in
      enterococci isolated from perirectal samples can be completed in approximately 4
      h. Novel pyrosequencing assays can provide data regarding the presence of
      multidrug-resistant M. tuberculosis directly from positive mycobacterial broth
      cultures in <1 day. These data can assist physicians in both therapeutic and
      infection control decisions.

PMID- 17205453
TI  - An approach to prevention of infectious diseases during military deployments.
AB  - The US military conducts missions that range from major ground combat operations
      to disaster and humanitarian relief efforts. A primary goal of military medical
      professionals is disease prevention, which can be made more difficult in the
      context of short preparation times and prolonged deployment duration. The
      military uses a 6-component approach to deployment medicine, emphasizing
      preparation, education, personal protective measures, vaccines, chemoprophylaxis,
      and surveillance in an attempt to prevent infectious diseases. Many of the
      components of military deployment medicine are applicable to civilian disaster
      relief and humanitarian missions.

PMID- 17205454
TI  - The impact of cirrhosis on CD4+ T cell counts in HIV-seronegative patients.
AB  - BACKGROUND: Studies of the progression liver fibrosis in human immunodeficiency
      virus (HIV) and hepatitis C virus-coinfected patients suggest that cirrhosis is
      associated with immunosuppression, as measured by low absolute CD4(+) T cell
      counts. However, we hypothesized that, in patients with advanced liver disease,
      low CD4(+) T cell counts may occur secondary to portal hypertension and splenic
      sequestration, regardless of the presence or absence of HIV infection. METHODS:
      Sixty HIV-seronegative outpatients with cirrhosis were enrolled during the period
      2001-2003 in a prospective, cross-sectional study of the association between
      liver disease and CD4(+) T cell counts and percentages. Demographic
      characteristics, liver disease-related characteristics, and laboratory results-
      including CD4(+) T cell parameters--were collected. RESULTS: A total of 39
      patients (65%) had a low CD4(+) T cell count; 26 patients (43%) and 4 patients
      (7%) had CD4(+) T cell counts <350 and <200 cells/mm(3), respectively. Abnormal
      CD4(+) T cell counts were associated with splenomegaly (P=.03), thrombocytopenia
      (P=.002), and leukopenia (P<.001). The percentage of CD4(+) T cells was normal in
      95% of patients who had a low absolute CD4(+) T cell count. CD4(+) T cell counts
      were significantly lower among cirrhotic patients than among 7638 HIV
      seronegative historic control subjects without liver disease. CONCLUSIONS:
      Cirrhosis is associated with low CD4(+) T cell counts in the absence of HIV
      infection. Discordance between low absolute CD4(+) T cell counts and normal
      CD4(+) T cell percentages may be attributable to portal hypertension and splenic
      sequestration. Our findings have significant implications for the use and
      interpretation of absolute CD4(+) T cell counts in HIV-infected patients with
      advanced liver disease.

PMID- 17205455
TI  - Cirrhosis is associated with low CD4+ T cell counts: implications for HIV
      infected patients with liver disease.

PMID- 17205456
TI  - CD4+ cell count 6 years after commencement of highly active antiretroviral
      therapy in persons with sustained virologic suppression.
AB  - BACKGROUND: Sustained suppression of the human immunodeficiency virus (HIV) type
      1 RNA load with the use of highly active antiretroviral therapy (HAART) results
      in immunologic improvement, but it is not clear whether the CD4(+) cell count
      increases to normal levels or whether it reaches a less-than-normal plateau. We
      characterized the increase in the CD4(+) cell count in patients in clinical
      practice who maintained sustained viral suppression for up to 6 years. METHODS:
      All patients were from the Johns Hopkins HIV Clinical Cohort, a longitudinal
      observational study of patients receiving primary HIV care in Baltimore,
      Maryland, who were observed for >1 year while receiving HAART and who had
      sustained suppression of the HIV RNA load at <400 copies/mL. We analyzed annual
      change in the CD4(+) cell count for up to 6 years after the start of HAART,
      stratified by baseline CD4(+) cell counts of < or =200, 201-350, >350
      cells/microL, and we assessed the development of clinical events (death and new
      acquired immunodeficiency syndrome-defining illness) by Kaplan-Meier analysis.
      RESULTS: A total of 655 patients were observed for a median of 46 months (range,
      13-72 months). The median change from baseline to most recent CD4(+) cell count
      was +274 cells/microL, with 92% of patients having an increase in CD4(+) cell
      count. By 6 years, the median CD4(+) cell count was 493 cells/microL among
      patients with baseline CD4(+) cell counts < or =200 cells/microL, 508
      cells/microL among those with baseline CD4(+) cell counts of 201-350
      cells/microL, and 829 cells/microL among those with baseline CD4(+) cell counts
      >350 cells/microL. In addition to baseline CD4(+) cell count, injection drug use
      and older age were associated with a lesser CD4(+) cell count response, and
      duration of therapy was associated with a greater CD4(+) cell count response.
      CONCLUSION: Only patients with baseline CD4(+) cell counts >350 cells/microL
      returned to nearly normal CD4(+) cell counts after 6 years of follow-up.
      Significant increases were observed in all CD4(+) cell count strata during the
      first year, but there was a lower plateau CD4(+) cell count at lower baseline
      CD4(+) cell strata. These data suggest that waiting to start HAART at lower
      CD4(+) cell counts will result in the CD4(+) cell count not returning to normal
      levels.

PMID- 17205457
TI  - Options for a second-line antiretroviral regimen for HIV type 1-infected patients
      whose initial regimen of a fixed-dose combination of stavudine, lamivudine, and
      nevirapine fails.
AB  - BACKGROUND: A fixed-dose combination of stavudine, lamivudine, and nevirapine is
      extensively used as an antiretroviral regimen in developing countries because of
      its affordability. Virological failure with this regimen has become more common,
      and a second-line regimen needs to be prepared in the national program. METHODS:
      Genotypic resistance testing was conducted among human immunodeficiency virus
      type 1 (HIV-1)-infected patients who experienced treatment failure with their
      first antiretroviral regimen (a fixed-dose combination of stavudine, lamivudine,
      and nevirapine) during 2003-2005. Patterns of resistance mutations and options
      for a second-line regimen were studied. RESULTS: We studied 98 patients (mean
      age, 35.2 years), of whom, 63% were male. The median duration of antiretroviral
      therapy was 20 months. The median HIV-1 RNA load at the time of virological
      failure detection was 4.1 log copies/mL. The prevalences of patients with > or =1
      major mutation conferring drug resistance to nucleoside reverse-transcriptase
      inhibitors and nonnucleoside reverse-transcriptase inhibitors were 95% and 92%,
      respectively. M184V was the most common nucleoside reverse-transcriptase
      inhibitor resistance mutation (observed in 89% of patients). Thymidine analogue
      mutations, K65R, and Q151M were observed in 37%, 6%, and 8% of patients,
      respectively. Patients with an HIV-1 RNA load of >4 log copies/mL at the time of
      treatment failure had higher prevalence of thymidine analogue mutations (P=.041),
      K65R (P=.031), and Q151M (P=.008) mutations. The second-line regimen was
      determined in a resource-limited setting where tenofovir and enfuvirtide are not
      available; the options were limited for 48% of patients. CONCLUSIONS: After
      experiencing treatment failure with a fixed-dose combination of stavudine,
      lamivudine, and nevirapine, almost all patients have lamivudine and nonnucleoside
      reverse-transcriptase inhibitor resistance. The options for a second-line regimen
      are limited for one-half of these patients. In resource-limited settings where
      availability of antiretroviral agents is limited, strategies for prevention of
      HIV-1 resistance are crucial. Early detection of virological failure may provide
      more options and better treatment outcomes.

PMID- 17205458
TI  - Drug resistance after failure of initial antiretroviral therapy in resource
      limited countries.

PMID- 17205459
TI  - Clinical utility of HIV standard genotyping among antiretroviral-naive
      individuals with unknown duration of infection.
AB  - In clinical settings, we have found a high rate of human immunodeficiency virus
      (HIV) drug resistance among antiretroviral-naive patients for whom the duration
      of infection was unknown. These high rates were most likely the result of both
      transmitted resistance and informal antiretroviral use, and they suggest that
      routine resistance testing among antiretroviral-naive patients would be a cost
      effective clinical practice.

PMID- 17205460
TI  - Screening for acute HIV infection: lessons learned.
AB  - Human immunodeficiency virus (HIV) nucleic acid testing is increasingly being
      used by researchers and public health screening programs to identify highly
      infectious, HIV antibody-negative individuals with acute HIV infection. We
      present cases to illustrate unusual instances of acute HIV screening, which
      include "window period" testing and the discovery of low-level HIV RNA.

PMID- 17205462
TI  - Safety of the rifampin and pyrazinamide short-course regimen for treating latent
      tuberculosis infection.

PMID- 17205464
TI  - Prevalence of antibodies against rubella virus in Spain.

PMID- 17205465
TI  - Efficacy of nitazoxanide for cyclosporiasis in patients with sulfa allergy.

PMID- 17205466
TI  - Combination therapy for sleeping sickness: a wake-up call.

PMID- 17205467
TI  - Two studies feed the debate on active surveillance for methicillin-resistant
      Staphylococcus aureus and vancomycin-resistant enterococci carriage: to screen or
      not to screen?

PMID- 17205468
TI  - Enfuvirtide antiviral activity despite rebound viremia and resistance mutations:
      fitness tampering or a case of persistent braking on entering?

PMID- 17205469
TI  - Equivalence trial of melarsoprol and nifurtimox monotherapy and combination
      therapy for the treatment of second-stage Trypanosoma brucei gambiense sleeping
      sickness.
AB  - BACKGROUND: Treatment of second-stage sleeping sickness relies mainly on
      melarsoprol. Nifurtimox has been successfully used to cure melarsoprol-refractory
      sleeping sickness caused by Trypanosoma brucei gambiense infection. METHODS: An
      open, randomized trial was conducted to test for equivalence between the standard
      melarsoprol regimen and 3 other regimens, as follows: standard melarsoprol
      therapy (3 series of 3.6 mg/kg/day intravenously [iv] for 3 days, with 7-day
      breaks between the series); 10-day incremental-dose melarsoprol therapy (0.6
      mg/kg iv on day 1, 1.2 mg/kg iv on day 2, and 1.8 mg/kg iv on days 3-10);
      nifurtimox monotherapy for 14 days (5 mg/kg orally 3 times per day); and
      consecutive 10-day melarsoprol-nifurtimox combination therapy (0.6 mg/kg iv
      melarsoprol on day 1, 1.2 mg/kg iv melarsoprol on day 2, and 1.2 mg/kg/day iv
      melarsoprol combined with oral 7.5 mg/kg nifurtimox twice a day on days 3-10).
      Primary outcomes were relapse, severe adverse events, and death attributed to
      treatment. RESULTS: A total of 278 patients were randomized. The frequency of
      adverse events was similar between the standard melarsoprol regimen and the other
      regimens. Encephalopathic syndromes occurred in all groups and caused all deaths
      that were likely due to treatment. Relapses (n=48) were observed only with the 3
      monotherapy regimens. CONCLUSION: A consecutive 10-day low-dose melarsoprol
      nifurtimox combination is more effective than the standard melarsoprol regimen.

PMID- 17205470
TI  - Improving methicillin-resistant Staphylococcus aureus surveillance and reporting
      in intensive care units.
AB  - BACKGROUND: Routine culturing of patients in intensive care units (ICUs) for
      methicillin-resistant Staphylococcus aureus (MRSA) identifies unrecognized
      carriers and facilitates timely isolation. However, the benefit of surveillance
      in detecting prevalent and incident carriers likely varies among ICUs. In
      addition, many assessments underestimate the incidence of acquisition by
      including prevalent carriers in the at-risk population. METHODS: We performed a
      retrospective cohort study using accurate at-risk populations to evaluate the
      range of benefit of admission and weekly surveillance cultures in detecting
      otherwise unrecognized MRSA in 12 ICUs in 5 states. RESULTS: We assessed 142 ICU
      months. Among the 12 ICUs, the admission prevalence of imported MRSA was 5%-21%,
      with admission surveillance providing 30%-135% increases in rates of detection.
      The monthly hospital-associated incidence was 2%-6%, with weekly surveillance
      providing 7%-157% increases in detection. The common practice of reporting
      incidence using the total number of patients or total patient-days underestimated
      incidence by one-third. Surgical ICUs had lower MRSA importation but higher MRSA
      incidence. Overall, routine surveillance prevented the misclassification of 17%
      (unit range, 11%-29%) of "incident" carriers, compared with clinical cultures,
      and increased precaution days by 18% (unit range, 11%-91%). CONCLUSIONS: Routine
      surveillance significantly increases the detection of MRSA, but this benefit is
      not uniform across ICUs, even with high compliance and the use of correct
      denominators.

PMID- 17205471
TI  - Improving the assessment of vancomycin-resistant enterococci by routine
      screening.
AB  - BACKGROUND: As infection with vancomycin-resistant enterococci (VRE) increases in
      hospitals, knowledge about VRE reservoirs and improved accuracy of epidemiologic
      measures are needed. Many assessments underestimate incidence by including
      prevalent carriers in at-risk populations. Routine surveillance cultures can
      substantially improve prevalence and incidence estimates, and assessing the range
      of improvement across diverse units is important. METHODS: We performed a
      retrospective cohort study using accurate at-risk populations to evaluate the
      range of benefit of admission and weekly surveillance cultures in detecting
      unrecognized VRE in 14 patient-care units. RESULTS: We assessed 165 unit-months.
      The admission prevalence of VRE was 2.2%-27.2%, with admission surveillance
      providing 2.2-17-fold increased detection. Medical units were significantly more
      likely to admit VRE carriers than were surgical units. Monthly incidence was 0.8%
      9.7%, with weekly surveillance providing 3.3-15.4-fold increased detection. The
      common practice of reporting incidence using the total number of patients, rather
      than patients at risk, underestimated incidence by one-third. Overall, routine
      surveillance prevented the misclassification of 43.0% (unit range, 0%-85.7%) of
      "incident" carriers on the basis of clinical cultures alone and increased VRE
      precaution days by 2.4-fold (unit range, 2.0-2.6-fold). CONCLUSIONS: Routine
      surveillance markedly increases the detection of VRE, despite variability across
      patient-care units. Correct denominators prevent the substantial underestimation
      of incidence.

PMID- 17205472
TI  - Diversity and antibiotic resistance among nonvaccine serotypes of Streptococcus
      pneumoniae carriage isolates in the post-heptavalent conjugate vaccine era.
AB  - BACKGROUND: In response to the selective pressure of pneumococcal conjugate
      vaccine, increased asymptomatic carriage of antibiotic-nonsusceptible nonvaccine
      serotypes (NVTs) has been observed. Possible mechanisms include de novo
      acquisition of resistance, serotype switching, introduction of new clones, and
      expansion of existing clones. METHODS: To investigate the process of increased
      antibiotic nonsusceptibility among replacing serotypes, we applied multilocus
      sequence typing to samples of 126 and 222 pneumococci collected in 2001 and 2004,
      respectively, from the nasopharynges of children <7 years of age in 16
      Massachusetts communities. RESULTS: We found no evidence of penicillin resistance
      due to either serotype switching or de novo acquisition. Nonetheless, resistance
      increased through the expansion of previously recognized clones of NVTs,
      particularly in serotypes 19A, 15A, and 35B. In 19A, several unrelated clones
      increased in frequency, whereas, in the other 2 serotypes, single resistant
      lineages were responsible for the increased prevalence of resistant strains.
      CONCLUSIONS: The decreased prevalence of antibiotic resistance with the
      introduction of heptavalent pneumococcal conjugate vaccine is likely to be
      partially eroded over time as vaccine-included serotypes are replaced by
      resistant clones of NVTs. The clinical significance of this will depend on the
      pathogenic potential of replacing clones to cause local (e.g., otitis media) or
      invasive disease.

PMID- 17205473
TI  - Group B Streptococcus bacteremia elicits beta C protein-specific IgMand IgG in
      humans.
AB  - Group B Streptococcus (GBS) beta C protein elicits protective antibodies in
      experimental animals, making beta C protein an attractive component of a human
      GBS glycoconjugate vaccine. We determined whether natural exposure to beta C
      protein elicits antibodies in humans. Geometric mean concentrations (in
      micrograms per milliliter) of beta C-specific immunoglobulin (Ig) M and IgG as
      determined by enzyme-linked immunosorbent assay were similar in serum from 16
      colonized (0.82 and 0.76, respectively) and 48 age-matched noncolonized (0.96 and
      0.74, respectively) pregnant women. Serum from 3 women with beta C GBS bacteremia
      had significantly higher levels of IgM (6.0) and IgG (52.9) (P=.01 and 0.01,
      respectively). Invasive disease but not colonization elicits beta C-specific IgM
      and IgG.

PMID- 17205474
TI  - Gene-expression patterns in whole blood identify subjects at risk for recurrent
      tuberculosis.
AB  - BACKGROUND: The majority of patients with tuberculosis who comply with
      appropriate treatment are cured. However, approximately 5% subsequently have a
      repeat disease episode, usually within 2 years of successful combination therapy.
      Presently, there is no way of predicting which patients will experience a
      relapse. METHODS: We identified 10 subjects who had previously experienced
      recurrent tuberculosis and carefully matched them to cured subjects who had had
      only 1 episode of tuberculosis, to patients with active tuberculosis, and to
      latently infected healthy subjects. We compared their ex vivo whole-blood gene
      expression profiles by use of DNA array technology and confirmed the results by
      use of quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).
      RESULTS: The 4 clinical tuberculosis groups exhibited distinct patterns of gene
      expression. The gene-transcript profiles of the patients with recurrent
      tuberculosis were more similar to those of the patients with active tuberculosis
      than to those of the cured or latently infected subjects. Discriminant analysis
      of a training data set showed that 9 genes were sufficient to classify the
      subjects. We confirmed that measurement of the expression of these genes by qRT
      PCR can accurately discriminate between subjects in a test set of samples.
      CONCLUSIONS: A simple test based on gene-expression patterns may be used as a
      biomarker of cure while identifying patients who are at risk for relapse. This
      would facilitate the introduction of new tuberculosis drugs.

PMID- 17205475
TI  - Enteroaggregative Escherichia coli virulence markers: positive association with
      distinct clinical characteristics and segregation into 3 enteropathogenic E. coli
      serogroups.
AB  - BACKGROUND: Enteroaggregative Escherichia coli (EAEC) are a heterogeneous
      category of emerging pathogens associated with acute and persistent diarrhea.
      METHODS: We performed a case-control study to evaluate the association of EAEC
      strains and their virulence markers with infantile diarrhea in Brasilia, Brazil.
      RESULTS: Of the EAEC markers that were tested, only EAEC heat-stable toxin
      (EAST1), protein involved in colonization (Pic), and the CVD432 sequence showed
      positive correlation with diarrhea; however, these virulence traits presented
      associations with distinct clinical characteristics. Although CVD432-positive
      strains were associated with persistent diarrhea, EAST1-positive strains were
      statistically correlated with acute diarrhea only in children >6 months of age.
      Typical EAEC strains were found with equal frequency in case patients and control
      subjects. O antigens of enteropathogenic E. coli (EPEC) were also sought, and the
      data showed that the EAEC markers are frequently segregated into 3 EPEC
      serogroups: O126, O128, and O158. CONCLUSIONS: The presence of EPEC O antigens
      along with EAEC markers influenced the positive association of E. coli strains
      with diarrhea. Concerning the detection of the AA phenotype, the CVD432 sequence
      presented a low positive predictive value, regardless of its high specificity as
      a marker.

PMID- 17205476
TI  - Escape from immune surveillance by Capnocytophaga canimorsus.
AB  - Capnocytophaga canimorsus, a commensal bacterium from dogs' mouths, can cause
      septicemia or meningitis in humans through bites or scratches. Here, we describe
      and characterize the inflammatory response of human and mouse macrophages on C.
      canimorsus infection. Macrophages infected with 10 different strains failed to
      release tumor necrosis factor (TNF)- alpha and interleukin (IL)-1 alpha .
      Macrophages infected with live and heat-killed (HK) C. canimorsus 5 (Cc5), a
      strain isolated from a patient with fatal septicemia, did not release IL-6, IL-8,
      interferon- gamma , macrophage inflammatory protein-1 beta , and nitric oxide
      (NO). This absence of a proinflammatory response was characterized by the
      inability of Toll-like receptor (TLR) 4 to respond to Cc5. Moreover, live but not
      HK Cc5 blocked the release of TNF- alpha and NO induced by HK Yersinia
      enterocolitica. In addition, live Cc5 down-regulated the expression of TLR4 and
      dephosphorylated p38 mitogen-activated protein kinase. These results highlight
      passive and active mechanisms of immune evasion by C. canimorsus, which may
      explain its capacity to escape from the host immune system.

PMID- 17205477
TI  - Interruption of enfuvirtide in HIV-1 infected adults with incomplete viral
      suppression on an enfuvirtide-based regimen.
AB  - Many antiretroviral drugs continue to exert an anti-human immunodeficiency virus
      (HIV) benefit in the presence of drug resistance mutations. The degree to which
      enfuvirtide exerts continued antiviral activity in the presence of incomplete
      viral suppression has not been defined. To address this question, 25 subjects
      interrupted enfuvirtide while remaining on a stable background regimen.
      Enfuvirtide interruption was associated with an immediate but limited increase in
      plasma HIV-1 RNA levels. Enfuvirtide resistance waned rapidly in the absence of
      drug pressure and was no longer detectable by week 16 in most individuals. These
      data indicate that enfuvirtide has measurable antiviral activity in the setting
      of incomplete viral suppression. Although enfuvirtide resistance mutations are
      associated with significant fitness defects in vivo, the clinical significance of
      these mutations remains undefined.

PMID- 17205478
TI  - Phenotypic susceptibility to didanosine is associated with antiviral activity in
      treatment-experienced patients with HIV-1 infection.
AB  - OBJECTIVE: We investigated the relationship between human immunodeficiency virus
      (HIV) phenotypic susceptibility to didanosine and the antiviral activity of
      didanosine (ddI) in the JAGUAR study. METHODS: Baseline plasma HIV phenotypic
      susceptibility to ddI was assessed using a phenotype assay of patients randomized
      to receive ddI or placebo for 4 weeks in addition to their current regimen.
      Phenotypic susceptibility scores (PSSs) were then calculated for each sample.
      Associations between PSS and week 4 reductions in plasma HIV-1 RNA load or
      virologic response were assessed using linear regression and Jonckherre's test
      and the Wilcoxon and Cochran-Armitage tests, respectively. RESULTS: In the ddI
      arm, a significant association between reduction in viral load and continuous PSS
      was observed (P<.0001). Using distinct categories, an increasing fold change (FC)
      in susceptibility to ddI was strongly associated with smaller reductions in
      plasma HIV-1 RNA load (P<.0001). The proportion of virologic responders was 83%
      (15/18) for patients with a ddI FC < or =1.3, 50% (33/66) for patients with an FC
      of 1.3-2.2, and 29% (4/14) for patients with an FC > or =2.2 (P=.0008). After we
      determined these findings, 3 ddI FC categories were defined using 1.3 and 2.2 as
      thresholds. CONCLUSIONS: The relationship between phenotypic susceptibility to
      ddI and reduction in plasma HIV-1 RNA load describes a continuum. The
      establishment of a lower clinical cutoff at 1.3 and an upper clinical cutoff at
      2.2 are clinically relevant.

PMID- 17205479
TI  - Persistence of HIV-1 variants with multiple protease inhibitor (PI)-resistance
      mutations in the absence of PI therapy can be explained by compensatory fixation.
AB  - OBJECTIVE: To investigate the mechanism explaining the persistence of human
      immunodeficiency virus (HIV) type 1 variants with multiple protease inhibitor
      (PI)-resistance mutations in the absence of PI therapy. METHODS: Longitudinal
      genotypic analyses were performed on sequential samples obtained from 2 HIV-1
      infected patients who had stopped PI therapy for 4 years. Replication capacity
      (RC) was determined using recombinant viruses. Subsequently, the effect that
      changing individual protease mutations back to wild type has on RC was analyzed.
      RESULTS: We observed prolonged persistence (up to 4 years) of viruses with
      multiple protease mutations after PI therapy was stopped, despite the fact that
      the RC of the viruses was severely reduced. Forcing the virus to evolve toward
      wild type by changing individual protease mutations to wild type was
      unsuccessful, because all variants displayed a decreased RC in comparison with
      that of their predecessors. CONCLUSIONS: We propose compensatory fixation as a
      mechanism for the in vivo persistence of variants with multiple PI-resistance
      mutations in the absence of PI therapy. Viruses with multiple PI mutations have
      (partially) compensated for the initial loss in RC. Therefore, reversion of a
      single mutation causes a (further) reduction in RC and, as a consequence, the
      route to wild type is blocked.

PMID- 17205480
TI  - Reconstitution of herpes simplex virus-specific T cell immunity in HIV-infected
      patients receiving highly active antiretroviral therapy.
AB  - Production of herpes simplex virus (HSV)-specific interferon- gamma by peripheral
      blood mononuclear cells (PBMCs) of HSV-seropositive healthy donors and human
      immunodeficiency virus-infected persons was determined by use of ELISPOT. The
      mean +/- SD number of spot-forming cells/10(6) PBMCs was 314 +/- 74 in 11 healthy
      donors, 360 +/- 69 in 3 long-term nonprogressors (LTNPs), 186 +/- 52 in 9 newly
      diagnosed patients, and 181 +/- 59 in 33 patients who were receiving highly
      active antiretroviral therapy (HAART) for a median period of 30 months (range, 1
      109 months). In 9 patients monitored prospectively while receiving virologically
      and immunologically successful first-line HAART, the number of spot-forming cells
      increased by 5.6/month (95% confidence interval, 1.2-9.9 [P=.01]) and 21.3/100
      CD4 cells/mm(3) gained (95% confidence interval, 13.8-28.7 [P<.0001]). Responses
      were correlated with LTNP status and CD4 cell count.

PMID- 17205481
TI  - Rapid, real-time detection of acute HIV infection in patients in Africa.
AB  - BACKGROUND: We conducted a prospective study to evaluate methods of detecting
      clients with sexually transmitted diseases (STDs) who were acutely coinfected
      with human immunodeficiency virus (HIV) in Lilongwe, Malawi. METHODS: After
      informed consent was obtained, all clients with acute STDs were offered voluntary
      HIV counseling and testing by 2 rapid antibody tests. Samples from rapid test
      negative or -discordant subjects were pooled (50 : 5 : 1) and tested for HIV RNA.
      Western blots were performed on all rapid test-discordant specimens with
      detectable HIV RNA. A subset of specimens received p24 antigen testing with
      standard and/or ultrasensitive methods. Patients with possible acute HIV
      infection were followed to confirm seroconversion. RESULTS: A total of 1450
      clients (34% female and 66% male) agreed to testing, of whom 588 (40.55%) had
      established HIV infection and 21 (1.45%) had acute infection. Discordant rapid
      antibody tests identified 7 of 21 (33.3% sensitivity), standard p24 antigen
      identified 12 of 16 (75% sensitivity), and ultrasensitive p24 antigen identified
      15 of 17 (88% sensitivity) acute cases. By definition, the sensitivity of the RNA
      assay was 100%. CONCLUSIONS: Real-time pooled RNA testing for the detection of
      acute HIV infection is feasible in resource-limited settings. However, parallel
      rapid testing and p24 antigen testing are technologically simpler and together
      may detect approximately 90% of acute cases.

PMID- 17205482
TI  - Absolute count and percentage of CD4+ lymphocytes are independent predictors of
      disease progression in HIV-infected persons initiating highly active
      antiretroviral therapy.
AB  - BACKGROUND: Highly active antiretroviral therapy (HAART) is recommended when the
      absolute CD4(+) T lymphocyte count is <200 cells/mm(3), and it should be
      considered when that count is > or =200, although the optimal timing when it is >
      or =200 is unclear. Because preliminary data had suggested that a low CD4(+) T
      lymphocyte percentage (%CD4) is associated with disease progression in persons
      initiating HAART who have a higher absolute CD4, we sought to further
      characterize the predictive utility of %CD4. METHODS: We conducted an
      observational study of persons in Collaborations in HIV Outcomes Research/US
      cohort who initiated their first HAART regimen between 1997 and 2004, received >
      or =30 days of therapy, and had baseline values of absolute CD4, %CD4, and HIV-1
      RNA. Cox proportional-hazards models determined associations between %CD4 and
      disease progression (to either a new AIDS-defining event [ADE] or death).
      RESULTS: Of 1891 persons, 11% were female and 18% were African American; the
      median age was 38 years. Median follow-up was 55 months (interquartile range, 23
      83 months), and 468 (25%) had disease progression. Multivariable analysis
      including age, race, sex, HIV-1 RNA, prior antiretroviral therapy, probable route
      of infection, prior ADE, absolute CD4, and %CD4 was performed; prior ART
      (P<.0001), injection-drug use (P=.04), lower absolute CD4 (P=.002), and lower
      %CD4 (P=.002) predicted disease progression. CONCLUSIONS: %CD4 at initiation of
      the first HAART regimen predicted disease progression independent of absolute
      CD4; %CD4 may be used to determine the timing of HAART.

PMID- 17205483
TI  - The nonstructural 5A protein of hepatitis C virus genotype 1b does not contain an
      interferon sensitivity-determining region.
AB  - BACKGROUND: The nonstructural (NS) 5A protein of hepatitis C virus (HCV) has been
      suggested to contain an interferon (IFN) sensitivity-determining region (ISDR).
      METHODS: We studied whether the degree of viral decline on day 1 is associated
      with differences in NS5A amino acid sequences among patients receiving IFN-
      alpha. RESULTS: Phylogenetic analyses of the full-length protein and of
      functional domains showed no relationship between the baseline protein sequence
      and the antiviral response. NS5A quasispecies sequences showed no differences in
      the number of mutations in the putative ISDR relative to a prototype sequence
      between responders and nonresponders or according to IFN- alpha antiviral
      efficacy. No relationship was found between antiviral efficacy at 24 h and the
      baseline sequence of any NS5A region. Amino acid changes were observed in a few
      cases at 24 h in both responders and nonresponders, but no consistent pattern of
      amino acid shifts was observed, ruling out the possibility that IFN- alpha
      selected IFN-resistant variants. CONCLUSION: Our findings show that there is no
      ISDR in the HCV genotype 1 NS5A protein and that the NS5A sequence does not
      influence the capacity of IFN- alpha to block viral replication. The findings do
      not rule out a role for NS5A in subsequent viral clearance.

PMID- 17205484
TI  - A prospective longitudinal study of polyomavirus shedding in lung-transplant
      recipients.
AB  - BACKGROUND: Polyomavirus infection causes renal dysfunction after kidney
      transplantation, but it has not been thoroughly investigated in nonrenal solid
      organ transplantation. METHODS: Fifty lung-transplant recipients provided
      prospective urine and blood samples over the course of 17 months. Samples were
      analyzed for BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) using
      conventional polymerase chain reaction (PCR), sequence analysis, and quantitative
      real-time PCR. RESULTS: Thirty-one (62%) of 50 patients had polyomavirus detected
      in at least 1 urine specimen, including 16 (32%) for BKV, 12 (24%) for JCV, and 6
      (12%) for SV40. Mean BKV loads (5.0 log(10) copies/mL) did not differ from those
      of JCV (5.7 log(10) copies/mL; P=.38), but SV40 loads (2.5 log(10) copies/mL)
      were lower than those of BKV (P=.006) and JCV (P=.002). Blood samples were
      negative. Infection with individual polyomaviruses or polyomavirus infection in
      aggregate was not associated with reduced creatinine clearance. Patients not
      shedding polyomavirus had better survival than patients shedding polyomavirus
      (P=.049). CONCLUSIONS: Polyomaviruses BKV and JCV were commonly detected in urine
      from lung-transplant recipients. SV40 was found in 12% of patients but was shed
      at a lower frequency and with lower viral loads than the other viruses.
      Polyomavirus infection was not associated with renal dysfunction.

PMID- 17205485
TI  - Detection of active human herpesvirus-6 infection in the brain: correlation with
      polymerase chain reaction detection in cerebrospinal fluid.
AB  - One-half of bone-marrow transplant (BMT) and stem-cell transplant recipients have
      reactivation of latent human herpesvirus (HHV)-6 2-4 weeks after transplant.
      Although the detection of viral DNA, RNA, and antigen in brain material confirmed
      active HHV-6 variant B infection, peak viral loads in cerebrospinal fluid (CSF)
      and serum occurred 2-4 weeks before death and decreased to low levels before or
      at autopsy. All autopsy samples consistently demonstrated HHV-6 active infection
      in the hippocampus. Astrocytic cells positive for viral antigen provided support
      for an HHV-6-specific tropism for hippocampal astrocytes. HHV-6 DNA in CSF and
      serum may not reflect the level of active viral infection in the brain after BMT.

PMID- 17205487
TI  - Effect of signal-to-noise ratio and spectral linewidth on metabolite
      quantification at 4 T.
AB  - The accuracy and precision of measurements of metabolite concentrations from
      short echo-time spectra has previously been characterized at l.5 T as a function
      of signal-to-noise ratio (SNR) and peak linewidth. The purpose of this study was
      to characterize the systematic error in quantification of metabolite
      concentrations associated with linewidth and SNR for the major metabolites of
      interest in the short echo-time 1H-MR spectrum at 4 T. Simulated 4 T LASER
      localized spectra (TE = 46 ms) were generated with full width at half maximum
      (FWHM) over the range 4-14 Hz, and SNR over the range 5-500 by adding 100
      Gaussian-distributed noise realizations at each combination of SNR and linewidth.
      Linewidth and SNR were treated as independent parameters, and therefore an
      increase in linewidth at a constant SNR resulted in increased metabolite areas.
      All spectra were fitted in the time domain using identical prior-knowledge and
      relative parameter starting values. Six metabolites (N-acetylaspartate,
      glutamate, creatine, myo-inositol, glycerophosphocholine, phosphocholine) were
      quantified with >90% accuracy and <10% standard deviation at SNR = 10 for
      linewidths ranging from 8 to 14 Hz FWHM. These simulations did not consider
      additional sources of variation, including eddy current artifacts, incomplete
      macromolecule baseline removal, and incomplete water suppression. Regardless, the
      results show that metabolite quantification from 4 T short echo-time 1H-MRS is
      sensitive to SNR and linewidth.

PMID- 17205486
TI  - Pathogenesis of Aspergillus fumigatus and the kinetics of galactomannan in an in
      vitro model of early invasive pulmonary aspergillosis: implications for
      antifungal therapy.
AB  - BACKGROUND: Little is known about the pathogenesis of invasive pulmonary
      aspergillosis and the relationship between the kinetics of diagnostic markers and
      the outcome of antifungal therapy. METHODS: An in vitro model of the human
      alveolus, consisting of a bilayer of human alveolar epithelial and endothelial
      cells, was developed. An Aspergillus fumigatus strain expressing green
      fluorescent protein was used. Invasion of the cell bilayer was studied using
      confocal and electron microscopy. The kinetics of culture, polymerase chain
      reaction, and galactomannan were determined. Galactomannan was used to measure
      the antifungal effect of macrophages and amphotericin B. A mathematical model was
      developed, and results were bridged to humans. RESULTS: A. fumigatus penetrated
      the cellular bilayer 14-16 h after inoculation. Galactomannan levels were
      inextricably tied to fungal invasion and were a robust measure of the antifungal
      effect of macrophages and amphotericin B. Neither amphotericin nor macrophages
      alone was able to suppress the growth of A. fumigatus; rather, the combination
      was required. Monte Carlo simulations showed that human dosages of amphotericin B
      of at least 0.6 mg/kg were required to achieve adequate drug exposure.
      CONCLUSIONS: This model provides a strategy by which relationships among
      pathogenesis, immunological effectors, and antifungal drug therapy for invasive
      pulmonary aspergillosis may be further understood.

PMID- 17205488
TI  - Standardized T2* map of normal human heart in vivo to correct T2* segmental
      artefacts.
AB  - A segmental, multislice, multi-echo T2* MRI approach could be useful in heart
      iron-overloaded patients to account for heterogeneous iron distribution,
      demonstrated by histological studies. However, segmental T2* assessment in heart
      can be affected by the presence of geometrical and susceptibility artefacts,
      which can act on different segments in different ways. The aim of this study was
      to assess T2* value distribution in the left ventricle and to develop a
      correction procedure to compensate for artefactual variations in segmental
      analysis. MRI was performed in four groups of 22 subjects each: healthy subjects
      (I), controls (II) (thalassemia intermedia patients without iron overload),
      thalassemia major patients with mild (III) and heavy (IV) iron overload. Three
      short-axis views (basal, median, and apical) of the left ventricle were obtained
      and analyzed using custom-written, previously validated software. The myocardium
      was automatically segmented into a 16-segment standardized heart model, and the
      mean T2* value for each segment was calculated. Punctual distribution of T2* over
      the myocardium was assessed, and T2* inhomogeneity maps for the three slices were
      obtained. In group I, no significant variation in the mean T2* among slices was
      found. T2* showed a characteristic circumferential variation in all three slices.
      The effect of susceptibility differences induced by cardiac veins was evident,
      together with low-scale variations induced by geometrical artefacts. Using the
      mean segmental deviations as correction factors, an artefact correction map was
      developed and used to normalize segmental data. The correction procedure was
      validated on group II. Group IV showed no significant presence of segmental
      artefacts, confirming the hypothesis that susceptibility artefacts are additive
      in nature and become negligible for high levels of iron overload. Group III
      showed a greater variability with respect to normal subjects. The correction map
      failed to compensate for these variations if both additive and percentage-based
      corrections were applied. This may reinforce the hypothesis that true
      inhomogeneity in iron deposition exists.

PMID- 17205489
TI  - Randomized clinical trial of the effects on anal function of Milligan-Morgan
      versus Ferguson haemorrhoidectomy (Br J Surg 2006; 93: 1208-1214).

PMID- 17205491
TI  - Non-patient factors related to rates of ruptured appendicitis.
AB  - BACKGROUND: Adult rates of ruptured appendicitis vary from 13.2 to 41.9 per cent
      in urban hospitals, despite controlling for individual factors. This suggests an
      effect of hospital organization. Surgeons report that appendicectomies may be
      delayed because of lack of access to operating rooms. METHODS: Combining
      interviews with hospital personnel and information from medical records for 1998
      1999, a cross-sectional study using logistic regression, taking hospital
      clustering of patients into account, was conducted on 861 patients from 12
      hospitals. Hospitals were grouped into organizational models. The diagnostic
      information was recoded to ensure interhospital validity. RESULTS: Hospitals with
      high activity and volumes of patients, but without an operating room designated
      for urgent surgery, were associated with a significantly higher risk of
      peritonitis (P<0.050). Time to surgery was very long in all hospitals,
      particularly time after departure from the emergency department and for elderly
      patients. CONCLUSION: Organizational characteristics, in unfavourable
      combinations, influence the course of time-dependent diseases such as
      appendicitis. Difficulties in gaining access to operating rooms, even for urgent
      operations, have emerged. Delays in treatment must be addressed when planning
      healthcare reforms.

PMID- 17205492
TI  - PTQ Implants in the treatment of faecal soiling.

PMID- 17205493
TI  - A protocol is not enough to implement an enhanced recovery programme for
      colorectal resection.
AB  - BACKGROUND: Single-centre studies have suggested that enhanced recovery can be
      achieved with multimodal perioperative care protocols. This international
      observational study evaluated the implementation of an enhanced recovery
      programme in five European centres and examined the determinants affecting
      recovery and length of hospital stay. METHODS: Four hundred and twenty-five
      consecutive patients undergoing elective open colorectal resection above the
      peritoneal reflection between January 2001 and January 2004 were enrolled in a
      protocol that defined multiple perioperative care elements. One centre had been
      developing multimodal perioperative care for 10 years, whereas the other four had
      previously undertaken traditional care. RESULTS: The case mix was similar between
      centres. Protocol compliance before and during the surgical procedure was high,
      but it was low in the immediate postoperative phase. Patients fulfilled
      predetermined recovery criteria a median of 3 days after operation but were
      actually discharged a median of 5 days after surgery. Delay in discharge and the
      development of major complications prolonged length of stay. Previous experience
      with fast-track surgery was associated with a shorter hospital stay. CONCLUSION:
      Functional recovery in 3 days after colorectal resection could be achieved in
      daily practice. A protocol is not enough to enable discharge of patients on the
      day of functional recovery; more experience and better organization of care may
      be required.

PMID- 17205494
TI  - The Ulcerated Leg Severity Assessment score for prediction of venous leg ulcer
      healing.
AB  - BACKGROUND: The aim of the study was to create a reliable scoring system for the
      prediction of venous ulcer healing in patients treated with compression. METHODS:
      A prospective baseline study to identify risk factors for venous ulcer healing
      was undertaken between March 1999 and August 2001. All patients were treated with
      multilayer compression. A number of variables were related to 24-week healing
      rates. A Cox regression model was used to identify risk factors that predicted
      ulcer healing, from which a scoring system was developed and validated
      prospectively between February 2004 and March 2005. RESULTS: In the baseline
      study of 229 patients, patient age, ulcer chronicity and venous refill time (VRT)
      of 20 s or less were identified as risk factors. Using these factors and hazard
      ratios from the Cox regression analysis, the following formula was devised:
      Ulcerated Leg Severity Assessment (ULSA) score=age+chronicity-50 (when VRT is
      greater than 20 s). Patients with an ULSA score of 50 or less had higher 24-week
      ulcer healing rates than those with higher scores in both the baseline study
      (P<0.001, log rank test) and the validation study performed in 86 patients
      (P=0.007, log rank test). CONCLUSION: The ULSA score may help to identify
      patients with venous ulcers unlikely to respond to conventional treatment who
      could be offered alternative therapy.

PMID- 17205495
TI  - Outcome of patients with huge hepatocellular carcinoma after primary resection
      and treatment of recurrent lesions.
AB  - BACKGROUND: Tumour recurrence is common after hepatic resection of hepatocellular
      carcinomas (HCCs) greater than 10 cm in diameter. This study evaluated the
      outcome of patients with huge HCC after primary resection and treatment of
      recurrent lesions. METHODS: A retrospective review was undertaken of clinical
      data for 100 patients with huge HCC who underwent liver resection. RESULTS:
      Mean(s.d.) tumour diameter was 13.3(3.0) cm; 80 per cent were single lesions.
      Systematic and non-systematic resections were performed in 80 and 20 per cent of
      patients respectively, with R0 resection achieved in 86 per cent. Overall 1-, 3-
      and 5-year disease-free survival rates were 43, 26 and 20 per cent respectively.
      Risk factors for HCC recurrence were resection margin less than 1 cm and
      macrovascular invasion. Extensive tumour necrosis of 90 per cent or more after
      preoperative transarterial chemoembolization was not a prognostic factor. Some 85
      per cent of patients with recurrence received various treatments, and these
      patients had a longer post-recurrence survival than those who were not treated.
      Overall 1-, 3- and 5-year survival rates were 66, 44 and 31 per cent
      respectively. CONCLUSION: In patients with huge HCC, hepatic resection combined
      with active treatment for recurrence resulted in longer-term survival. Frequent
      protocol-based follow-up appears to be beneficial for the early detection and
      timely treatment of recurrence.

PMID- 17205496
TI  - Minimally invasive parathyroidectomy using the lateral focused mini-incision
      technique without intraoperative parathyroid hormone monitoring.
AB  - BACKGROUND: Minimally invasive parathyroidectomy (MIP) involves scan-directed
      removal of a single adenoma through a 2.0-cm mini-incision without intraoperative
      monitoring. The aim of this study was to analyse the outcomes of MIP using such a
      simplified technique. METHODS: The study group comprised 500 consecutive patients
      undergoing MIP via a lateral mini-incision from August 2000 to September 2005.
      Levels of parathyroid hormone (PTH) were measured after operation solely to aid
      informed discharge. RESULTS: Some 97.4 per cent of patients were initially cured
      by MIP. Eight patients remained hypercalcaemic and a further five were
      normocalcaemic on the day after surgery but became hypercalcaemic again within 3
      months of the procedure. Eleven of these patients were cured with subsequent re
      exploration. Analysis of postoperative PTH data indicated that, at best, the use
      of intraoperative PTH measurement during surgery would have increased the cure
      rate by only a further 1 per cent. Three (0.6 per cent) of 500 patients had
      permanent recurrent laryngeal nerve palsy after MIP. CONCLUSION: MIP performed by
      the lateral focused mini-incision technique, without the use of intraoperative
      PTH monitoring, is a safe and effective procedure that results in outcomes equal
      to those of bilateral neck exploration.

PMID- 17205497
TI  - Optical adjuncts for enhanced colonoscopic diagnosis.
AB  - BACKGROUND: Optical techniques using previously unexploited properties of light
      interaction with tissue may be valuable in the detection, diagnosis and staging
      of colorectal neoplasia. METHODS: A Medline search (1990 to present) was
      conducted on optical diagnostics in the detection of colorectal neoplasia. The
      reference list of each identified article was reviewed for further relevant
      papers. RESULTS AND CONCLUSION: Chromoendoscopy is the only optical adjunct to
      colonoscopy that has been tested in large randomized clinical trials. It improves
      the detection of small and flat colorectal adenomas, and of neoplasia in chronic
      ulcerative colitis and hereditary non-polyposis colorectal cancer. All other
      techniques are the subject of ongoing research and the practicality of population
      screening with any of the methods has yet to be established. Optical techniques
      may, however, permit immediate clinical diagnosis, removing the need for
      histological analysis. They may also improve the diagnosis of early colonic
      neoplasia.

PMID- 17205498
TI  - MicroRNAs and cancer.
AB  - BACKGROUND: MicroRNAs (miRNAs) are small sequences of RNA, 21 to 22 nucleotides
      long, that have been discovered recently. They are produced from areas of the
      human genome that were previously thought to have no function. These sequences
      now appear to be important in the regulation of many fundamental processes.
      Evidence has recently emerged that deregulated miRNA activity is associated with
      human cancers. METHODS: The English literature was searched using PubMed for
      publications relevant to miRNAs and cancer. Relevant references from identified
      publications were also sourced. These publications were reviewed to identify
      existing evidence for the role of miRNAs in cancer. RESULTS: miRNAs inhibit the
      translation of mRNA from many target genes involved in cancer development. This
      leads to changes in the levels of protein encoded by these target genes and
      drives the development of cancer. The genes that produce miRNAs are frequently
      located in regions of the genome that are either lost, or amplified, in cancer
      cells. CONCLUSION: Determination of the miRNA expression profile in cancer
      tissues should lead to a better understanding of the genetic pathways involved in
      tumour development.

PMID- 17205499
TI  - Nerve management during open hernia repair.
AB  - BACKGROUND: Peroperative identification and subsequent division or preservation
      of the inguinal nerves during open hernia repair may influence the incidence of
      chronic postoperative pain. METHODS: A systematic literature review was performed
      to identify studies investigating the influence of different types of nerve
      management. RESULTS: Based on three randomized studies the pooled mean percentage
      of patients with chronic pain after identification and division of the
      ilioinguinal nerve was similar to that after identification and preservation of
      the ilioinguinal nerve. Two cohort studies suggested that the incidence of
      chronic pain was significantly lower after identification of all inguinal nerves
      compared with no identification of any nerve. Another cohort study reported a
      significant difference in the incidence of chronic pain in favour of
      identification and facultative pragmatic division of the genital branch of the
      genitofemoral nerve compared with no identification at all. CONCLUSION: The
      nerves should probably be identified during open hernia repair. Division of and
      preservation of the ilioinguinal nerve show similar results.

PMID- 17205500
TI  - Redefining the R1 resection in pancreatic cancer (Br J Surg 2006; 93:1232-1237).

PMID- 17205501
TI  - Contralateral recurrence and prognostic factors in familial non-BRCA1/2
      associated breast cancer (Br J Surg 2006; 93: 961-968).

PMID- 17205504
TI  - Letter 2: randomized clinical trial assessing the effect of Doppler-optimized
      fluid management on outcome after elective colorectal resection (Br J Surg 2006;
      93: 1069-1076).

PMID- 17205505
TI  - Letter 1: randomized clinical trial assessing the effect of Doppler-optimized
      fluid management on outcome after elective colorectal resection (Br J Surg 2006;
      93: 1069-1076).

PMID- 17205507
TI  - An integrated system-wide strategy for quality improvement in cancer surgery.

PMID- 17205508
TI  - Natural orifice transluminal endoscopic surgery.

PMID- 17205510
TI  - OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer.
AB  - OCT-4 (also known as POU5F1) is a key regulator of self-renewal in embryonic stem
      cells. Regarding the new cancer stem cell concept, the expression of such genes
      is potentially correlated with tumorigenesis and can affect some aspects of tumor
      behavior, such as tumor recurrence or resistance to therapies. Although OCT-4 has
      been introduced as a molecular marker for germ cell tumors, little is known about
      its expression in somatic cancers. Here, we have investigated the potential
      expression of OCT-4 in bladder cancer. We used semiquantitative RT-PCR to examine
      the expression of OCT-4 in 32 tumors, 13 apparently nontumor tissues taken from
      the margin of tumors and 9 normal urothelial tissues. The expression of OCT-4 at
      protein level was further determined by Western blotting and immunohistochemical
      (IHC) analysis. OCT-4 expression was detected in almost all examined tumors
      (31/32), but at much lower level (p<0.001) in some nonneoplastic samples (6/22).
      A significantly strong correlation of 0.6 has been observed between OCT-4
      expression and the presence of tumors (p<0.001). Western blot analysis further
      confirmed the expression of OCT-4 in tumor biopsies. According to IHC results,
      OCT-4 is primarily localized in the nuclei of tumor cells, with no or low
      immunoreactivity in nontumor cells. Our study demonstrated, for the first time,
      the expression of OCT-4 in bladder cancer and a further clue to the involvement
      of embryonic genes in carcinogenesis.

PMID- 17205511
TI  - Free PSA isoforms and intact and cleaved forms of urokinase plasminogen activator
      receptor in serum improve selection of patients for prostate cancer biopsy.
AB  - Clinicians currently use simple cut-points, such as serum prostate-specific
      antigen (PSA) >or=4 ng/ml, to decide whether to recommend further work-up for
      prostate cancer (PCa). As an alternative strategy, we evaluated multivariable
      models giving probabilities of a PCa diagnosis based on PSA and several
      circulating novel biomarkers. We measured total PSA, free PSA (fPSA), fPSA
      subfractions (single-chain fPSA-I and multichain fPSA-N), total human glandular
      kallikrein 2 (hK2) and full-length and cleaved forms of soluble urokinase
      plasminogen activator receptor (suPAR) in pretreatment serum from 355 men
      referred for prostate biopsy. Age and total PSA were combined in a "base"
      regression model to predict biopsy outcome. We then compared this base model to
      models supplemented by various combinations of circulating markers, using
      concordance index (AUC) to measure diagnostic discrimination. PCa prediction was
      significantly enhanced by models supplemented by measurements of suPAR fragments
      and fPSA isoforms. Addition of these markers improved bootstrap-corrected AUC
      from 0.611 for a cut-point and 0.706 for the base model to 0.754 for the full
      model (p=0.005). This improved diagnostic accuracy was also seen in subanalysis
      of patients with PSA 2-9.99 ng/ml and normal findings on DRE (0.652 vs. 0.715,
      p=0.039). In this setting, hK2 did not add diagnostic information. Measurements
      of individual forms of suPAR and PSA isoforms contributed significantly to
      discrimination of men with PCa from those with no evidence of malignancy.

PMID- 17205512
TI  - Expression of CCR9 in HTLV-1+ T cells and ATL cells expressing Tax.
AB  - Adult T-cell leukemia (ATL) is a highly aggressive mature CD4+ T-cell malignancy
      that is etiologically associated with human T-lymphotropic virus Type 1 (HTLV-1).
      ATL is characterized by frequent infiltration of lymph nodes, spleen, liver, skin
      and gut. Previously, we and others have shown that the majority of ATL cases are
      strongly positive for CCR4, which may explain the frequent skin invasion of ATL.
      Here, we examined whether ATL cells express CCR9, which is involved in T-cell
      homing to the gastrointestinal tract. Human T cell lines carrying HTLV-1
      consistently expressed CCR9 together with the HTLV-1-encoded transcriptional
      activator Tax. Although ATL cells freshly isolated from peripheral blood hardly
      expressed CCR9, ATL cells cultured for 1 day consistently expressed CCR9 in
      parallel with the upregulation of Tax. Induction of Tax by Cd2+ in JPX-9, a
      subline of Jurkat human T cell line carrying Tax under the control of
      metallothionein promoter, led to upregulation of CCR9. A luciferase reporter gene
      under the control of the CCR9 promoter was expressed by cotransfection of an
      expression vector for Tax or in Cd2+-treated JPX-9 cells. Furthermore,
      immunohistochemical staining demonstrated that ATL cells infiltrating
      gastrointestinal tract were frequently positive for CCR9. Collectively, CCR9 is
      inducible in ATL cells expressing Tax and may play a role in the gastrointestinal
      involvement of ATL.

PMID- 17205513
TI  - Mismatch repair polymorphisms and the risk of colorectal cancer.
AB  - Rare germline variants in mismatch repair genes have been linked to hereditary
      nonpolyposis colorectal cancer; however, it is unknown whether common
      polymorphisms in these genes alter the risk of colorectal cancer. To examine the
      association between common variants in mismatch repair genes and colorectal
      cancer, we conducted a case-cohort study within the CLUE II cohort. Four single
      nucleotide polymorphisms in 3 mismatch repair genes (MSH3 R940Q, MSH3 T1036A,
      MSH6 G39E and MLH1 I219V) were genotyped in 237 colorectal cancer cases and a
      subcohort of 2,189 participants. Incidence rate ratios (RRs) and 95% confidence
      intervals (95% CIs) for each polymorphism were estimated. The MSH3 1036A variant
      was found to be associated with an increased risk of colorectal cancer (RR=1.28,
      95% CI: 0.94-1.74 and RR=1.65, 95% CI: 1.01-2.70 for the AT and TT genotypes,
      respectively, with p(trend)=0.02), particularly proximal colon cancer. Although
      the MSH3 940Q variant was only weakly associated with colorectal cancer overall
      (p(trend)=0.07), it was associated with a significant increased risk of proximal
      colon cancer (RR=1.69, 95% CI: 1.10-2.61 and RR=2.68, 95% CI: 0.96-7.47 for the
      RQ and QQ genotypes, respectively with p(trend)=0.005). Processed meat intake
      appeared to modify the association between the MSH3 polymorphisms and colorectal
      cancer (p(interaction) < 0.10 for both). No association was observed with the
      MSH6 and MLH1 polymorphisms overall. This study suggests that common
      polymorphisms in the mismatch repair gene, MSH3, may increase the risk of
      colorectal cancer, especially proximal colon cancer.

PMID- 17205514
TI  - Human papillomavirus testing on self-sampled cervicovaginal brushes: an effective
      alternative to protect nonresponders in cervical screening programs.
AB  - Women not attending cervical screening programs are at increased risk of cervical
      cancer. We investigated in these nonresponders to what extent offering self
      sampling devices for cervicovaginal brushes for high-risk human papillomavirus
      (hrHPV) testing would induce participation and, if so, what the yield of
      precursor (i.e. CIN2 or worse) lesions following self-sampling would be. In
      addition, we assessed screening history of participants and costs per detected
      high-grade CIN2 or worse ("CIN2+") lesion in comparison to the regular program in
      the Netherlands. Nonresponders received a device for hrHPV testing (self-sampling
      group, n=2,546) or an extra recall for conventional cytology (control group,
      n=284). The percentage of self-sampling responders were compared with responders
      in the recall group. hrHPV positive self-sampling responders were invited for
      cytology and colposcopy. CIN2+ yield and costs per detected CIN2+ were evaluated.
      Active response was higher in the self-sampling than in the control group (34.2
      vs. 17.6%; p<0.001). hrHPV positive self-sampling responders were less likely to
      have a prior screening history than screening participants (p<0.001), indicating
      that they are regular nonresponders. hrHPV prevalence was similar (8.0 vs. 6.8%;
      p=0.11), but CIN2+ yield was higher in self-sampling responders compared to
      screening participants (1.67 vs. 0.97%; OR=2.93, 95% CI 1.48-5.80; p=0.0013).
      Costs per CIN2+ lesion detected via self-sampling were in the same range as those
      calculated for conventional cytological screening (euro 8,836 vs. euro 7,599).
      Offering self-sampling for hrHPV testing in nonresponders is an attractive
      adjunct to effectively increase population coverage of screening without the
      adverse effect of markedly increased costs per detected CIN2+ lesion.

PMID- 17205515
TI  - Gefitinib and chemotherapy combination studies in five novel human non small cell
      lung cancer xenografts. Evidence linking EGFR signaling to gefitinib antitumor
      response.
AB  - The epidermal growth factor receptor (EGFR) signaling pathway is often activated
      in NSCLC, and thus represents a promising therapeutic target. We studied the
      antitumor activity of gefitinib (Iressa), an orally active EGFR-tyrosine kinase
      inhibitor, alone and in combination with standard chemotherapy in 5 recently
      established human NSCLC xenografts with wild-type EGFR. Mice were treated with 2
      protocols of chemotherapy based on cisplatin (CDDP) combined with either
      gemcitabine (GEM) or vinorelbine (VNR). Gefitinib alone significantly inhibited
      tumor growth (TGI) in 4 of the 5 tumor xenografts (mean TGI of 58%, range: 25
      70%). CDDP+VNR alone failed to achieve any significant responses, while CDDP+GEM
      achieved significant responses in 2 xenografts (TGI of 93 and 47%). Addition of
      gefitinib to CDDP+GEM potentialized chemotherapy in the 3 CDDP+GEM-resistant
      xenografts, but did not potentialize the CDDP+VNR combination. The effect of
      gefitinib treatment on the activity of extra cellular-regulated kinase (Erk),
      Akt, JNK and p38 kinases was assessed in IC9LC11 and IC1LC131, two NSCLC
      xenografts selected for their sensitivity and resistance to gefitinib,
      respectively. In IC9LC11, gefitinib strongly inhibited Erk, Akt and Jnk
      phosphorylation, but P38 remained active. Inversely, in IC1LC131, Erk and Akt
      pathways remained active, while Jnk and P38 pathways were inhibited by gefitinib.
      The data indicate that the antitumor activity of gefitinib in NSCLC, alone or in
      combination with chemotherapy, is tumor-dependent and is influenced by downstream
      signaling events independent of EGFR status.

PMID- 17205516
TI  - CD133 positive hepatocellular carcinoma cells possess high capacity for
      tumorigenicity.
AB  - Recently increasing reported data have suggested that only a small subset of
      cancer cells possess capability to initiate malignancies including leukemia and
      solid tumors, which was based on investigation in these cells displaying a
      distinct surface marker pattern within the primary cancers. CD133 is a putative
      hematopoietic and neuronal stem-cell marker, which was also considered as a
      tumorigenic marker in brain and prostate cancer. We hypothesized that CD133 was a
      marker closely correlated with tumorigenicity, since it was reported that CD133
      expressed in human fetal liver and repairing liver tissues, which tightly
      associated with hepatocarcinogenesis. Our findings showed that a small population
      of CD133 positive cells indeed exists in human hepatocellular carcinoma (HCC)
      cell lines and primary HCC tissues. From SMMC-7721 cell line, CD133+ cells
      isolated by MACS manifested high tumorigenecity and clonogenicity as compared
      with CD133- HCC cells. The implication that CD133 might be one of the markers for
      HCC cancer stem-like cells needed further investigation.

PMID- 17205518
TI  - Regulation of P53 stability in p53 mutated human and mouse hepatoma cells.
AB  - The tumor suppressor p53 is frequently mutated in cancer. We have investigated
      the regulation of P53 in p53 wild type mouse hepatoma cells (line 55.1c), in p53
      heterozygeously mutated cells (56.1b) and in p53 defective cells (lines 56.1d,
      70.4 and HUH7) under various experimental settings. The basal levels of P53 were
      low in 55.1c cells, but nuclear accumulation occurred upon UV-irradiation.
      Similarly, UV-exposure induced stabilization of P53 in the heterozygeously p53
      mutated 56.1b hepatoma cells. By contrast, the 3 hepatoma lines, which lack
      transcriptionally active P53, demonstrated high basal nuclear concentrations of
      P53 protein and, unexpectedly, showed loss of P53 upon UV-irradiation. Expression
      of p53 mRNA was also decreased in p53 defective cells after 24 hr post UV
      irradiation, which may be linked to induction of apoptosis of the irradiated
      cells under these conditions. Other stressors like H2O2 also mediated a decrease
      in P53 concentration in p53 defective cells. This effect occurred at very low
      concentrations and was already detectable 1-2 hr after exposure of cells. There
      were no signs of apoptosis of H2O2-exposed cells at this time point and no
      significant changes in p53 mRNA or MDM2 level. These unexpected findings indicate
      a new aspect related to regulation of P53 stability in cells with a defect in the
      tumor suppressor protein.

PMID- 17205517
TI  - CENP-F expression is associated with poor prognosis and chromosomal instability
      in patients with primary breast cancer.
AB  - DNA microarrays have the potential to classify tumors according to their
      transcriptome. Tissue microarrays (TMAs) facilitate the validation of biomarkers
      by offering a high-throughput approach to sample analysis. We reanalyzed a high
      profile breast cancer DNA microarray dataset containing 96 tumor samples using a
      powerful statistical approach, between group analyses. Among the genes we
      identified was centromere protein-F (CENP-F), a gene associated with poor
      prognosis. In a published follow-up breast cancer DNA microarray study,
      comprising 295 tumour samples, we found that CENP-F upregulation was
      significantly associated with worse overall survival (p<0.001) and reduced
      metastasis-free survival (p<0.001). To validate and expand upon these findings,
      we used 2 independent breast cancer patient cohorts represented on TMAs. CENP-F
      protein expression was evaluated by immunohistochemistry in 91 primary breast
      cancer samples from cohort I and 289 samples from cohort II. CENP-F correlated
      with markers of aggressive tumor behavior including ER negativity and high tumor
      grade. In cohort I, CENP-F was significantly associated with markers of CIN
      including cyclin E, increased telomerase activity, c-Myc amplification and
      aneuploidy. In cohort II, CENP-F correlated with VEGFR2, phosphorylated Ets-2 and
      Ki67, and in multivariate analysis, was an independent predictor of worse breast
      cancer-specific survival (p=0.036) and overall survival (p=0.040). In conclusion,
      we identified CENP-F as a biomarker associated with poor outcome in breast cancer
      and showed several novel associations of biological significance.

PMID- 17205519
TI  - Coffee consumption and the risk of colorectal cancer: a prospective cohort study
      in Japan.
AB  - An inverse association between coffee consumption and the risk of colorectal
      cancer has been reported in several case-control studies, but results from
      prospective cohort studies have been inconclusive. We conducted a prospective
      cohort study among a Japanese population to clarify the association between
      coffee consumption and the risk of colorectal cancer incidence. We used data from
      the Miyagi Cohort Study for this analysis. Usable self-administered
      questionnaires about coffee consumption were returned from 22,836 men and 24,769
      women, aged 40-64 years, with no previous history of cancer. We used the Cox
      proportional-hazard regression model to estimate hazard ratios and 95% confidence
      intervals. During 11.6 years of follow-up (425,303 person-years), we identified
      457 cases of colorectal cancer. Coffee consumption was not associated with the
      incidence of colorectal, colon or rectal cancer. The multivariate-adjusted hazard
      ratio (95% confidence interval) of colorectal cancer incidence for 3 or more cups
      of coffee per day as compared with no consumption was 0.95 (0.65-1.39) for men
      and women (p for trend = 0.55), 0.91 (0.56-1.46) for men (p for trend = 0.53) and
      1.16 (0.60-2.23) for women (p for trend = 0.996). Coffee consumption was also not
      associated with incidence of either proximal or distal colon cancer. We conclude
      that coffee consumption is not associated with the incidence risk of colorectal
      cancer in the general population in Japan.

PMID- 17205520
TI  - Inhibition of lung carcinogenesis by 1alpha,25-dihydroxyvitamin D3 and 9-cis
      retinoic acid in the A/J mouse model: evidence of retinoid mitigation of vitamin
      D toxicity.
AB  - 9-cis-Retinoic acid (9cRA) and 1alpha,25-dihydroxyvitamin D3 (1,25D) show promise
      as potential chemopreventive agents. We examined 9cRA and 1,25D, alone and in
      combination, for their potential to inhibit carcinogen (NNK)-induced lung
      carcinogenesis in A/J mice. A/J mice (n=14/group) were treated with 9cRA (7.5,
      15, or 30 mg/kg diet), 1,25D (2.5 or 5.0 microg/kg diet), or a combination of
      9cRA (15 mg/kg diet) plus 1,25D (2.5 microg/kg diet) for 3 weeks before and 17
      weeks after carcinogen injection. Lung tumor incidence, tumor multiplicity,
      plasma 1,25D levels and kidney expression of vitamin D 24-hydroxylase (CYP24)
      were determined. Compared to carcinogen-injected controls, mice receiving 9cRA
      supplementation had significantly lower tumor multiplicity at all doses
      (decreased 68-85%), with body weight loss at the higher doses of 9cRA. Mice
      receiving 1,25D supplementation had significantly lower tumor incidence
      (decreased 36 and 82%) and tumor multiplicity (decreased 85 and 98%), but
      experienced significant body weight loss, kidney calcium deposition, elevated
      kidney CYP24 expression and decreased fasting plasma 1,25D levels. Although,
      there was no apparent influence on chemopreventive efficacy, addition of 9cRA to
      1,25D treatment effectively prevented the weight loss and kidney calcification
      associated with 1,25D treatment alone. These data demonstrate that 9cRA and
      1,25D, alone or combined, can inhibit lung tumor promotion in the A/J mouse
      model. Combining 1,25D with 9cRA has the potential to mitigate the toxicity of
      1,25D, while preserving the significant effect of 1,25D treatment against lung
      carcinogenesis. The underlying mechanism behind this effect does not appear to be
      related to retinoid modulation of vitamin D catabolism.

PMID- 17205521
TI  - A retrospective case-control study of the use of hormone-related supplements and
      association with breast cancer.
AB  - Hormone-related supplements (HRS), many of which contain phytoestrogens, are
      widely used to manage menopausal symptoms, yet their relationship with breast
      cancer risk has generally not been evaluated. We evaluated whether use of HRS was
      associated with breast cancer risk, using a population-based case-control study
      in 3 counties of the Philadelphia metropolitan area consisting of 949 breast
      cancer cases and 1,524 controls. Use of HRS varied significantly by race, with
      African American women being more likely than European American women to use any
      herbal preparation (19.2% vs. 14.7%, p=0.003) as well as specific preparations
      including black cohosh (5.4% vs. 2.0%, p=0.003), ginseng (12.5% vs. 7.9%,
      p<0.001) and red clover (4.7% vs. 0.6%, p<0.001). Use of black cohosh had a
      significant breast cancer protective effect (adjusted odds ratio 0.39, 95% CI:
      0.22-0.70). This association was similar among women who reported use of either
      black cohosh or Remifemin (an herbal preparation derived from black cohosh;
      adjusted odds ratio 0.47, 95% CI: 0.27-0.82). The literature reports that black
      cohosh may be effective in treating menopausal symptoms, and has antiestrogenic,
      antiproliferative and antioxidant properties. Additional confirmatory studies are
      required to determine whether black cohosh could be used to prevent breast
      cancer.

PMID- 17205522
TI  - Low adiponectin levels are associated with renal cell carcinoma: a case-control
      study.
AB  - Adiponectin is a novel endogenous insulin sensitizer, secreted by mature
      adipocytes. Circulating levels of adiponectin are inversely associated with
      obesity and insulin resistance. Because obesity is a risk factor for renal cell
      carcinoma (RCC), we hypothesized that low adiponectin levels are associated with
      RCC. To evaluate this hypothesis, we conducted a case- control study of 70
      patients with histologically confirmed RCC and 280 healthy controls matched by
      gender, age and county of residence. Study subjects were interviewed and blood
      samples were collected during a 32-month period in Athens, Greece. Serum
      adiponectin levels were statistically, significantly and inversely associated
      with RCC when compared with controls (OR=0.76, p=0.05) and this association
      remained practically unchanged after controlling for BMI; the introduction of
      waist to hip ratio along with adiponectin in the multiple logistic regression
      analysis model rendered the association between adiponectin and RCC risk
      insignificant, indicating that altered levels of adiponectin may mediate the
      effect of central or intra-abdominal obesity on RCC. Prospective studies as well
      as studies exploring underlying mechanisms are needed to fully explore the role
      of adiponectin in predicting future risk of RCC in humans.

PMID- 17205523
TI  - In vivo mutagenicity of vinyl carbamate and ethyl carbamate in lung and small
      intestine of F1 (Big Blue x A/J) transgenic mice.
AB  - Vinyl carbamate (VC) is a metabolite of ethyl carbamate (EC), a chemical found in
      alcoholic beverages and fermented foods. We undertook this study to: (i) evaluate
      the ability of both EC and VC to induce gene mutations in lung and various
      extrapulmonary tissues, and (ii) identify the type of mutations induced by the
      two compounds in various tissues. F1 (Big Blue x A/J) transgenic mice harboring
      the lambda cII transgene were used for identification and quantitation of
      mutations in vivo. Time-course studies in lung showed a plateau in mutant
      frequency (MF) 4 weeks after VC treatment, at which time mutations were fixed and
      were about 4-fold higher than in controls. Dose-dependent increases in MF were
      detected in the lung and small intestine (SI) after treatment with 15-75 mg/kg,
      i.p., of VC. VC was mutagenic in the lung and SI at doses of 45, 60 and 75 mg/kg.
      Sequencing of the cII gene in lung and SI showed that VC induced mainly A:T-->G:C
      transitions and A:T-->T:A transversions. EC was also mutagenic in the lung at 500
      and 1,000 mg/kg and elicited mainly G:C-->A:T transitions. A VC dose of 60 mg/kg
      elicited a similar level of MF as an EC dose of 1,000 mg/kg. At 4 weeks after
      treatment, neither VC nor EC elicited mutations in the colon, bone marrow or
      kidney. These results demonstrated that VC and EC are mutagenic in vivo and
      affirm that VC is a more potent mutagen than EC.

PMID- 17205524
TI  - Differential effects of naturally occurring and synthetic organoselenium
      compounds on biomarkers in androgen responsive and androgen independent human
      prostate carcinoma cells.
AB  - Epidemiological studies and clinical trials show that selenium supplementation
      results in reduction of prostate cancer incidence; however, the form of selenium
      and mechanisms underlying protection remain largely unknown. Toward this end, we
      compared the effects of naturally occurring selenomethionine (SM) and Se
      methylselenocysteine (MSC) and synthetic 1,4-phenylenebis(methylene)selenocyanate
      (p-XSC) and p-xylylbis(methylselenide) p-XMS) organoselenium compounds in
      androgen responsive (AR) LNCaP and its androgen independent clone (AI) LNCaP C4-2
      human prostate carcinoma cells on cell growth, secretion of prostate specific
      antigen (PSA), intracellular redox status and genomic profiles with emphasis on
      identifying redox sensitive genes. Both p-XSC and p-XMS reduced cell number and
      total protein concentration compared to control-treated AR and AI cells, while SM
      and MSC exhibited no effect on growth of AR and AI cells. SM, p-XSC and p-XMS but
      not MSC inhibited levels of secreted PSA in AR cells. SM, MSC and p-XMS increased
      glutathione (GSH) levels in AI LNCaP cells. By contrast, in both cell types, only
      p-XSC significantly decreased GSH concentrations to <50% of control suggesting
      either an increase in intracellular oxidative stress or a change in GSH/GSSG
      ratio. On the basis of RT-PCR analysis, SM and p-XSC increased p53 gene
      expression by 2-fold in AR cells but not in AI cells and only SM enhanced
      epidermal growth factor receptor in AR cells. Depending on the structure,
      organoselenium compounds exhibit differential effects on growth, PSA secretion,
      oxidative stress and selective gene responses in human prostate cancer cells and
      suggest the potential of developing novel organoselenium compounds as
      chemopreventive agents in models of human prostate cancer.

PMID- 17205525
TI  - Enhanced levels of glutathione and protein glutathiolation in rat tongue
      epithelium during 4-NQO-induced carcinogenesis.
AB  - High glutathione (GSH) levels are commonly found in oral tumors and are thought
      to play an important role in tumorigenesis. While posttranslational binding of
      GSH to cellular proteins (protein glutathiolation) has recently been recognized
      as an important redox-sensitive regulatory mechanism, no data currently exist on
      this process during carcinogenesis. Our goal was to determine the effects of 4
      nitroquinoline-N-oxide (4-NQO)-induced carcinogenesis on tongue levels of protein
      bound and free GSH and related thiols in the rat. Male F-344 rats (6 weeks of
      age) were administered either 4-NQO (20 ppm) in drinking water or tap water alone
      (controls) for 8 weeks. Twenty-four weeks after cessation of 4-NQO, squamous cell
      carcinomas of the tongue were observed in all rats. The levels of both free and
      bound GSH in tumors, as well as in adjacent tissues, were 2- to 3-fold greater
      than in tongue epithelium from control rats (p < 0.05). Prior to tumor formation,
      at 8 weeks after cessation of 4-NQO, hyperplasia, dysplasia and carcinoma in situ
      were observed in 100%, 25% and 12.5% of 4-NQO-treated rats, respectively. At this
      early stage of carcinogenesis, levels of free and bound GSH were increased 50%
      compared with tongue tissues from control rats (p<0.05). Glutathione disulfide
      (GSSG) levels were also 2-fold greater in tongue tissues from 4-NQO treated vs.
      control rats (p<0.05). Altogether, these results suggest that protein
      glutathiolation, together with GSH and GSSG levels, are induced during oral
      carcinogenesis in the rat possibly as a result of enhanced levels of oxidative
      stress.

PMID- 17205526
TI  - Esophageal cancer in Central and Eastern Europe: tobacco and alcohol.
AB  - Esophageal cancer mortality rates in Central and Eastern Europe have been
      increasing steadily and are expected to increase further in the future. To
      evaluate the role of risk factors for esophageal cancer in this population, a
      multicenter study was conducted, with investigation of tobacco and alcohol as one
      of the principal aims. We have included 192 squamous cell carcinoma (SCC) and 35
      adenocarcinoma cases of the esophagus diagnosed at designated hospitals in 5
      centers from Romania, Russia, the Czech Republic and Poland. Controls were
      frequency matched from patients in the same hospital as the cases (n=1,114). Our
      results showed that the risk of esophageal SCC may be increased by approximately
      7-fold for current smokers (OR=7.41, 95% CI 3.98-13.79) and by 3-fold for ever
      alcohol drinkers (OR=2.86, 95% CI 1.06-7.74). Dose-response relations were
      evident for both the frequency and duration of tobacco and of alcohol on the risk
      of esophageal SCC. Risk estimates for tobacco smoking were highest for lower
      esophageal SCCs, while risk estimates for alcohol drinking were highest for upper
      esophageal SCCs; though differences were not statistically significant. For
      adenocarcinoma of the esophagus, our results suggested a more modest increase in
      risk because of tobacco smoking than that for SCC of the esophagus and no
      association with alcohol consumption, although our sample size was small. A
      synergistic interaction between tobacco and alcohol was observed for the risk of
      esophageal SCC, highlighting the importance of both factors for esophageal
      cancers in Central and Eastern Europe.

PMID- 17205527
TI  - Human retinoblastoma is not caused by known pRb-inactivating human DNA tumor
      viruses.
AB  - Retinoblastomas occur as the consequence of inactivation of the tumor suppressor
      retinoblastoma protein (pRb), classically upon biallelic inactivation of the RB1
      gene locus. Recently, human papillomavirus (HPV) genomic DNA has been detected in
      retinoblastomas. To investigate the possibility that oncoproteins encoded by pRb
      inactivating DNA tumor viruses play a role in the pathogenesis of human
      retinoblastoma, 40 fresh-frozen tumors were analyzed for the presence of HPV,
      adenovirus (HAdV) and polyomavirus (BKV, JCV and SV40) genomic DNA sequences by
      real-time polymerase chain reaction (PCR). Tumors were screened for genetic and
      epigenetic alterations in all 27 exons of the RB1 gene locus and promoter by
      exonic copy number detection, sequencing and methylation-specific PCR of the
      promoter region. Retinoblastoma tumors from children with bilateral familial
      (n=1), bilateral nonfamilial (n=1) and unilateral nonfamilial (n=38) disease were
      analyzed. Inactivating modifications to the RB1 gene locus were identified on
      both the alleles in 27 tumors, one allele in 8, and neither allele in 5 cases. A
      median of over 107,000 tumor cells were analyzed for viral genomic DNA in each
      PCR reaction. All tumor samples were negative for 37 HPV types, 51 HAdV types,
      BKV and JCV genomic sequences. Very low copy number (0.2-260 copies per 100,000
      tumor cells) SV40 genomic DNA detected in 8 of 39 samples was demonstrated to be
      consistent with an artifact of plasmid-derived SV40. In contrast to recent
      reports, we obtained substantial quantitative evidence indicating that neither
      HPV nor any other pRb-inactivating human DNA tumor viruses play a role in the
      development of retinoblastoma, regardless of RB1 genotype.

PMID- 17205528
TI  - HPV integration begins in the tonsillar crypt and leads to the alteration of p16,
      EGFR and c-myc during tumor formation.
AB  - The prevalence of human papillomavirus (HPV) infection is high in the
      oropharyngeal mucosal regions, of which the tonsil is the most commonly affected.
      There may be a link between HPV and the pathogenesis of tonsillar cancer (TC),
      because of common anatomical characteristics between cervical and tonsillar
      cancer. We aimed to clarify whether HPV directly affects the oncogenesis and
      biologic behavior of TC by making a comparison between infection prevalence,
      physical status and viral loading numbers, and clinicopathologic prognostic
      factors. To compare HPV-related molecules between TC and tonsillitis (CFT), p16,
      survivin, HIF-1alpha, skp-1, cyclin A, cyclin B1, c-myc and EGFR were
      investigated. We observed a significant difference in HPV prevalence between 52
      TCs and 69 CFTs (73.1% vs. 11.6%), and most of the HPVs were type 16 (87.2%) and
      nonepisomal (94.1%). Most TCs associated with HPV arose from the tonsillar
      crypts, and tended to be inverted and poorly differentiated. Compared with HPV
      negative TC, HPV-positive TC showed a strong association with p16 overexpression
      (p<0.0001), and an inverse association with EGFR amplification (p=0.0478). HPV-16
      integration status was strongly associated with c-myc amplification (p=0.034) and
      HIF-1alpha overexpression (p=0.022). HPV-16 integration could be directly related
      to tonsillar carcinogenesis initially in tonsillar crypts, followed by cell cycle
      aberration such as p16 overexpression related to the G1-S phase.

PMID- 17205529
TI  - Gene transfer of the CD40-ligand to human dendritic cells induces NK-mediated
      antitumor effects against human carcinoma cells.
AB  - The CD40-ligand (CD40L) is a key molecule for the activation of dendritic cells
      (DCs), followed by the induction of DC maturation and cytokine production. Here
      we found that DC infected with adenovirus vector encoding human CD40L (CD40L-DC)
      displayed significantly higher levels of immune accessory molecules and IL-12
      production than did uninfected cells, and that CD40L-DC produced much higher
      levels of IFN-gamma. To investigate whether CD40L-DC-derived these soluble
      factors could stimulate NK cells without physical cell-to-cell contact, we
      cocultured NK cells with CD40L-DC in transwell culture plates. NK cells showed up
      regulated cytotoxic activity toward various squamous oral cell carcinoma (OSC-70,
      HSC-2, HSC-3), and we determined that both IL-12 and IFN-gamma contributed to the
      CD40L-DC-mediated NK cell activation. NK cells stimulated with CD40L-DC resulted
      in the induction of the cell surface expression of TRAIL, the production of IFN
      gamma and intracellular accumulation of granzyme B. The cytotoxic activity of NK
      cells stimulated with CD40L-DC could be mostly inhibited by neutralizing antibody
      for TRAIL and completely abrogated by the combination of antibody and exocytosis
      inhibitor, indicating that this was mainly mediated by a TRAIL-TRAIL-receptor
      interaction and granule exocytosis. Moreover, CD40L-DC-activated NK cells could
      induce up-regulation of a death-receptor TRAIL-R2 (DR5) and down-regulation of a
      decoy receptor TRAIL-R3 (DcR1) on carcinoma cells. Overall, these results have
      revealed that CD40L-DC could activate an innate immune reaction by stimulating NK
      cells followed by carcinoma cells, supporting that administration of CD40L-DC may
      have potential as an anticancer therapy.

PMID- 17205530
TI  - Nonsteroidal anti-inflammatory drugs and risk of lung cancer.
AB  - Regular aspirin and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use
      is associated with a reduced risk of colorectal cancer. The effect of NSAIDs on
      the risk of other cancers remains unclear. To evaluate whether use of aspirin or
      other specific NSAIDs protects against lung cancer, we conducted a case-control
      study nested in a cohort of subjects 40-84 years old in 1995-2004, without a
      diagnosis of cancer before the study start date, and with at least 2 years of
      enrollment with a general practitioner providing data to the The Health
      Improvement Network (THIN) database in the UK. Patients who had a first diagnosis
      of primary lung cancer during the study period were considered cases. A random
      sample of 10,000 controls was frequency-matched to the cases for age, sex and
      calendar year. The index date for exposure definition was 1 year before the date
      of diagnosis for cases and 1 year before a random date within the study period
      for controls. Relative risks and 95% confidence intervals were estimated using
      conditional logistic regression stratified for matching factors. Factors such as
      smoking, chronic obstructive pulmonary disease, cardiovascular diseases and body
      mass index were introduced in the model. We identified 4,336 cases with primary
      incident lung cancer (incidence rate 7.6 per 10,000 person-years). Compared with
      subjects with no prescription of non-aspirin NSAID prior to the index date, the
      risk of lung cancer was 0.76 (0.61-0.94) among those who received a prescription
      the previous year and had a treatment duration of at least 1 year. The
      corresponding relative risk was 1.15 (0.99-1.34) for aspirin. In conclusion,
      prescription of non-aspirin NSAIDs for at least 1 year might be associated with a
      slightly reduced risk of lung cancer. Aspirin was not associated with a risk
      reduction, perhaps due to residual confounding.

PMID- 17205531
TI  - Coffee and tea consumption and risk of hepatocellular carcinoma in Italy.
AB  - The role of coffee in the aetiology of hepatocellular carcinoma has raised great
      interest. In Italy, coffee consumption is high, thus allowing the investigation
      of the topic over a broad range of consumption. A hospital-based case-control
      study was conducted in Italy in 1999-2002, including 185 incidents,
      histologically confirmed cases of hepatocellular carcinoma aged 43-84 years.
      Controls were 412 subjects admitted to the same hospitals' networks for acute,
      non-neoplastic diseases unrelated to diet. Coffee and tea consumption were
      assessed using a validated food-frequency questionnaire. Odds ratios (ORs) and
      corresponding the 95% confidence intervals (CI) were computed using unconditional
      multiple logistic regression, adjusting for hepatitis viruses seropositivity,
      alcohol intake, smoking habits and other potential confounding factors. Compared
      to people who drunk <14 cups/week of coffee, the risk of hepatocellular carcinoma
      decreased for increasing levels of consumption (OR=0.4, 95% CI: 0.2-1.1 for
      >or=28 cups/week, p for trend = 0.02). In the present study, inverse relations
      were observed across strata of hepatitis C and, B virus infections and alcohol
      drinking. No significant association emerged with consumption of decaffeinated
      coffee (OR=0.7, 95% CI=0.2-2.5) or tea (OR=1.4, 95% CI=0.8-2.7). The present
      study supports the hypothesis of a favourable effect of coffee, though not
      decaffeinated coffee and tea, on the risk on hepatocellular carcinoma.

PMID- 17205532
TI  - Detection of tumor-specific DNA in blood and bone marrow plasma from patients
      with prostate cancer.
AB  - Tumor tissues, blood plasma and bone marrow (BM) aspirates of 57 prostate cancer
      patients (PCa) without clinical signs of overt metastases were assessed for LOH
      (loss of heterozygosity) by a PCR-based fluorescence microsatellite analysis,
      using a panel of 15 markers. Additionally, micrometastatic tumor cells in BM were
      monitored by an immunocytological cytokeratin assay. In total, 25 (44%), 32 (56%)
      and 41 (72%) of the patients had at least 1 LOH in their blood, BM and tumor
      samples, respectively. Among the informative cases, the frequency of LOH was
      highest in blood plasma for the markers D8S360 (18%) and D10S1765 (15%), and in
      BM plasma for THRB (24%) and D8S137 (22%). Comparison of blood plasma and BM with
      tumors showed discrepant results in 35% and 45% of patients, respectively.
      Whereas all LOHs at THRB in BM plasma were also detected in the autologous tumor
      tissues, LOHs at D6S474 and D11S898 in BM were not retrieved in the tumors. The
      comparison with established risk factors showed a correlation of borderline
      significance for LOH at D9S1748 in the BM aspirates (p=0.055) and a significant
      correlation in the tumor samples (p=0.004) with increasing pathologic Gleason
      scores. Interestingly, 22% of the PCa patients harbored tumor cells in their BM
      and tended (p=0.065) to have more frequent LOH (16%) in BM plasma compared to
      patients without tumor cells (9%). These data demonstrate, for the first time,
      the presence of free tumor-specific DNA in blood and BM of PCa patients and
      suggest a possible relationship to BM micrometastasis.

PMID- 17205533
TI  - Multiple peripheral artery occlusions in antiphospholipid syndrome.

PMID- 17205534
TI  - Aggressive T-cell large granular lymphocyte leukemia: a case report and review of
      the literature.
AB  - The majority of patients with T-cell large granular lymphocyte (LGL) leukemia
      will have an indolent clinical course. Herein, we report a case of an aggressive
      T-cell LGL leukemia in a previously healthy 42-year-old Caucasian male who
      presented with acute onset of B-symptoms, hepatosplenomegaly, lymphocytosis,
      moderate anemia, and thrombocytopenia. Immunophenotypically, the malignant cells
      co-expressed CD3(+)CD8(+)CD56(+) markers and the T-cell receptor beta (TCR beta)
      gene demonstrated clonal rearrangement. The patient was treated with an intensive
      chemotherapeutic regimen (hyper-CVAD) and he achieved a complete remission. A
      systematic review of all available English literature revealed 12 well-described
      cases of aggressive T-cell LGL leukemia suggesting that this variant is a new and
      distinct entity in the spectrum of LGL disorders.

PMID- 17205535
TI  - Association of acquired von Willebrand syndrome with AL amyloidosis.
AB  - Acquired loss of functional von Willebrand factor (VWF) has been termed the
      acquired von Willebrand syndrome (AVWS). AVWS is a rare adult-onset bleeding
      diathesis that is clinically similar to congenital von Willebrand disease (VWD),
      and occurs with a variety of autoimmune, lymphoproliferative, or
      myeloproliferative disorders. We have identified four patients with AVWS in
      association with immunoglobulin light chain (AL) amyloidosis. These patients,
      lacking any pre-existing or family history of abnormal bleeding, developed
      cutaneous, mucosal, or gastrointestinal bleeding in the course of their disease
      without deficiency of clotting factor X or other factors; the activated partial
      thromboplastin time (aPTT) was prolonged in three out of the four cases. Despite
      normal VWF antigen levels, VWF ristocetin cofactor activity (VWF:RCo) was low.
      Electrophoresis patterns of high molecular weight (HMW) VWF multimers were
      abnormal in two of the four cases. Two of the patients were treated with high
      dose intravenous melphalan followed by autologous stem cell transplantation
      (HDM/SCT) and achieved hematologic remission. In these two patients, the bleeding
      diathesis improved and the coagulation parameters normalized, confirming a causal
      relationship between the plasma cell dyscrasia and the AVWS. AVWS should be
      considered in AL amyloidosis patients with hemorrhagic diatheses and normal
      clotting factor levels.

PMID- 17205536
TI  - Lack of A563G (I188V) missense mutation in RIZ/ PRDM2 in human diffuse large B
      cell lymphomas.

PMID- 17205538
TI  - From ether theory to ether theology: Oliver Lodge and the physics of immortality.
AB  - This article follows the development of physicist Oliver Lodge's religio
      scientific worldview, beginning with his reticent attraction to metaphysics in
      the early 1880s to the full formulation of his "ether theology" in the late
      1890s. Lodge undertook the study of psychical phenomena such as telepathy,
      telekinesis, and "ectoplasm" to further his scientific investigations of the
      ether, speculating that electrical and psychical manifestations were linked
      phenomena that described the deeper underlying structures of the universe,
      beneath and beyond matter. For Lodge, to fully understand the ether was to force
      from the universe an ultimate Revelation, and psychical research, as the most
      modern and probatory science, was poised to replace religion as the means of that
      disclosure.

PMID- 17205537
TI  - Characterization of a 3;6 translocation associated with renal cell carcinoma.
AB  - The most frequent cause of familial clear cell renal cell carcinoma (RCC) is von
      Hippel-Lindau disease and the VHL tumor suppressor gene (TSG) is inactivated in
      most sporadic clear cell RCC. Although there is relatively little information on
      the mechanisms of tumorigenesis of clear cell RCC without VHL inactivation, a
      subset of familial cases harbors a balanced constitutional chromosome 3
      translocation. To date nine different chromosome 3 translocations have been
      associated with familial or multicentric clear cell RCC; and in three cases
      chromosome 6 was also involved. To identify candidate genes for renal
      tumorigenesis we characterized a constitutional translocation, t(3;6)(q22;q16.1)
      associated with multicentric RCC without evidence of VHL target gene
      dysregulation. Analysis of breakpoint sequences revealed a 1.3-kb deletion on
      chromosome 6 within the intron of a 2 exon predicted gene (NT_007299.434).
      However, RT-PCR analysis failed to detect the expression of this gene in
      lymphoblast, fibroblast, or kidney tumor cell lines. No known genes were
      disrupted by the translocation breakpoints but several candidate TSGs (e.g.,
      EPHB1, EPHA7, PPP2R3A RNF184, and STAG1) map within close proximity to the
      breakpoints.

PMID- 17205539
TI  - Schizophrenia as split personality/Jekyll and Hyde: the origins of the informal
      usage in the English language.
AB  - The entry into the English language of the informal usage of schizophrenia as
      split personality/Jekyll and Hyde is traced and commented upon. The metaphor of
      split personality is followed from Eugene Bleuler via his translators and the
      wider psychiatric community into the present day. It, and to a lesser extent the
      Jekyll-Hyde personality, is found to be as much a product of the psychological
      professions as a product of lay misinterpretation. The informal definition of
      schizophrenia as split personality has outlived the scientific theory with which
      it was initially associated.

PMID- 17205540
TI  - Burt's separated twins: the larger picture.

PMID- 17205542
TI  - Ribot, Binet, and the emergence from the anthropological shadow.
AB  - In the drive to establish a naturalistic psychology in France, anthropological
      assumptions about a hierarchy of physically determined racial groups with
      inherent psychological characteristics and about the nearly insurmountable
      retardation of primitive cultures permeated the work of the founder of French
      empirical psychology, Theodule Ribot. Assumptions about the correlation of brain
      mass and head size with intelligence affected Alfred Binet. The rise of sociology
      and challenges to existing theories of inheritance led Ribot to surrender
      fitfully some hereditarian assumptions. Binet's experimental caution and
      contemporary critiques of anthropometry tempered, but did not fully extinguish,
      his enthusiasm for psychophysical correlations.

PMID- 17205543
TI  - George Herbert Mead and the Allen controversy at the University of Wisconsin.
AB  - This essay uses previously unpublished correspondence of George Herbert Mead to
      tell the story of his involvement in the aftermath of a political dispute that
      took place at the University of Wisconsin during the years 1914-1915. It seeks
      thereby to clarify the historical significance of an article he published on this
      controversy in late 1915. Taken together with relevant information about the
      educational activities of William H. Allen of the New York Bureau of Municipal
      Research, Mead's correspondence and article throw helpful light upon his
      understanding of how an educational survey of a university should proceed; they
      also show how he went about the task of evaluating a failed attempt at such a
      survey.

PMID- 17205546
TI  - A proteomic analysis of adult rat bone reveals the presence of
      cartilage/chondrocyte markers.
AB  - The non-mineral component of bone matrix consists of 90% collagenous, 10% non
      collagenous proteins. These proteins regulate mineralization, growth, cell
      signaling and differentiation, and provide bone with its tensile strength.
      Expression of bone matrix proteins have historically been studied individually or
      in small numbers owing to limitations in analytical technologies. Current mass
      spectrometric and separations technologies allow a global view of protein
      expression patterns in complex samples. To our knowledge, no proteome profile of
      bone matrix has yet been reported. Therefore, we have used mass spectrometry as a
      tool to generate a profile of proteins present in the extracellular matrix of
      adult rat bone. Overall, 108 and 25 proteins were identified with high confidence
      in the metaphysis and diaphysis, respectively, using a bottom up proteomic
      technique. Twenty-one of these proteins were present in both the metaphysis and
      diaphysis including the bone specific proteins, osteocalcin, type I collagen,
      osteopontin, osteoregulin, and bone sialoprotein. Interestingly, type II
      collagen, a protein thought to be exclusively expressed in cartilage, was
      identified in both the metaphysis and diaphysis. This observation was validated
      by Western blot. Additionally, the presence of aggrecan, another protein
      expressed in cartilage was identified in the bone matrix extracts by Western
      blot. The proteome profile generated using this technology represents an initial
      survey of the acid soluble proteins of bone matrix which provides a reference for
      the analysis of deviations from the normal composition due to perturbations or
      disease states.

PMID- 17205547
TI  - Childhood malnutrition and growth in a rural area of Western Kenya.
AB  - An anthropometric survey was carried out on 1,383 school students aged 5-17 years
      in Suba district (a rural area of western Kenya). Body size and proportion were
      computed from height, weight, sitting height, arm circumference, and skinfolds.
      The aim of the study was to evaluate patterns of growth and nutritional status of
      the Luo population by assessment of the prevalence and trends of malnutrition
      among children and adolescents. Very few age-groups show significant sex
      differences for height, body weight, and arm muscle area. However, there are
      several differences in skinfold thicknesses and arm circumference, always with
      higher mean values in girls. Analysis of the nutritional status (weight-for-age,
      height-for-age, and BMI-for-age) shows significant differences among the age
      groups in both sexes. Boys present lower Z-scores than girls and there are higher
      percentages of malnourished subjects (stunted and underweight) among the males.
      The Luo data were compared with those of other African populations. Their body
      dimensions, nutritional status, and growth are similar to those of the other sub
      Saharan samples. In conclusion, the Luo children are generally undernourished at
      the older ages: adolescents (11-16 years of age) show the most severe
      undernutrition and the highest percentages of undernourished subjects. In
      addition to the higher risk of undernutrition in teenagers, an emerging problem
      of over-nutrition is evident among the younger age-groups, with a higher
      prevalence in females. These findings are discussed in light of sexual dimorphism
      in sensitivity to adverse environmental conditions.

PMID- 17205548
TI  - Population structure of the Classic period Maya.
AB  - This study examines the population structure of Classic period (A.D. 250-900)
      Maya populations through analysis of odontometric variation of 827 skeletons from
      12 archaeological sites in Mexico, Guatemala, Belize, and Honduras. The
      hypothesis that isolation by distance characterized Classic period Maya
      population structure is tested using Relethford and Blangero's (Hum Biol 62
      (1990) 5-25) approach to R matrix analysis for quantitative traits. These results
      provide important biological data for understanding ancient Maya population
      history, particularly the effects of the competing Tikal and Calakmul hegemonies
      on patterns of lowland Maya site interaction. An overall F(ST) of 0.018 is found
      for the Maya area, indicating little among-group variation for the Classic Maya
      sites tested. Principal coordinates plots derived from the R matrix analysis show
      little regional patterning in the data, though the geographic outliers of
      Kaminaljuyu and a pooled Pacific Coast sample did not cluster with the lowland
      Maya sites. Mantel tests comparing the biological distance matrix to a geographic
      distance matrix found no association between genetic and geographic distance. In
      the Relethford-Blangero analysis, most sites possess negative or near-zero
      residuals, indicating minimal extraregional gene flow. The exceptions were Barton
      Ramie, Kaminaljuyu, and Seibal. A scaled R matrix analysis clarifies that genetic
      drift is a consideration for understanding Classic Maya population structure. All
      results indicate that isolation by distance does not describe Classic period Maya
      population structure.

PMID- 17205549
TI  - A preliminary analysis of the DNA and diet of the extinct Beothuk: a systematic
      approach to ancient human DNA.
AB  - We have used a systematic protocol for extracting, quantitating, sexing and
      validating ancient human mitochondrial and nuclear DNA of one male and one female
      Beothuk, a Native American population from Newfoundland, which became extinct
      approximately 180 years ago. They carried mtDNA haplotypes, which fall within
      haplogroups X and C, consistent with Northeastern Native populations today. In
      addition we have sexed the male using a novel-sexing assay and confirmed the
      authenticity of his Y chromosome with the presence of the Native American
      specific Y-QM3 single nucleotide polymorphism (SNP). This is the first ancient
      nuclear SNP typed from a Native population in the Americas. In addition, using
      the same teeth we conducted a stable isotopes analysis of collagen and dentine to
      show that both individuals relied on marine sources (fresh and salt water fish,
      seals) with no hierarchy seen between them, and that their water sources were
      pooled or stored water. Both mtDNA sequence data and Y SNP data hint at possible
      gene flow or a common ancestral population for both the Beothuk and the current
      day Mikmaq, but more importantly the data do not lend credence to the proposed
      idea that the Beothuk (specifically, Nonosabasut) were of admixed (European
      Native American) descent. We also analyzed patterns of DNA damage in the clones
      of authentic mtDNA sequences; there is no tendency for DNA damage to occur
      preferentially at previously defined mutational hotspots, suggesting that such
      mutational hotspots are not hypervariable because they are more prone to damage.

PMID- 17205550
TI  - Isotopic evidence for age-related immigration to imperial Rome.
AB  - Oxygen stable isotope ratios (delta(18)O) have been determined in carbonate in
      paired first and third molar teeth from individuals (N = 61) who lived in the
      town of Portus Romae ("Portus") and who were buried in the necropolis of Isola
      Sacra (First to Third centuries AD) near Rome, Italy. We compare these analyses
      with data for deciduous teeth of modern Roman children. Approximately one-third
      of the archaeological sample has first molar (M1) values outside the modern
      range, implying a large rate of population turnover at that time, consistent with
      historical data. Delta (18)O(ap) values suggest that a group within the sample
      migrated to the area before the third molar (M3) crown had completely formed
      (i.e., between 10 and 17.5 years of age). This is the first quantitative
      assessment of population mobility in Classical antiquity. This study demonstrates
      that migration was not limited to predominantly single adult males, as suggested
      by historical sources, but rather a complex phenomenon involving families. We
      hypothesize that migrants most likely came from higher elevations to the East and
      North of Rome. One individual with a higher delta(18)O value may have come (as a
      child) from an area isotopically similar to North Africa.

PMID- 17205551
TI  - A formal test of linguistic and genetic coevolution in native Central and South
      America.
AB  - This paper investigates a mechanism of linguistic and genetic coevolution in
      Native Central and South America. This mechanism proposes that a process of
      population fissions, expansions into new territories, and isolation of ancestral
      and descendant groups will produce congruent language and gene trees. To evaluate
      this population fissions mechanism, we collected published mtDNA sequences for
      1,381 individuals from 17 Native Central and South American populations. We then
      tested the hypothesis that three well-known language classifications also
      represented the genetic structure of these populations. We rejected the
      hypothesis for each language classification. Our tests revealed linguistic and
      genetic correspondence in several shallow branches common to each classification,
      but no linguistic and genetic correspondence in the deeper branches contained in
      two of the language classifications. We discuss the possible causes for the lack
      of congruence between linguistic and genetic structure in the region, and
      describe alternative mechanisms of linguistic and genetic correspondence and
      their predictions.

PMID- 17205552
TI  - Identification of soluble CD14 as an endogenous agonist for Toll-like receptor 2
      on human astrocytes by genome-scale functional screening of glial cell derived
      proteins.
AB  - Human astrocytes express a limited repertoire of Toll-like receptor (TLR) family
      members including TLR1-4, which are expressed on the cell surface. Also, TLR3 but
      not TLR4 activation on astrocytes induces expression of several factors involved
      in neuroprotection and down-regulation of inflammation rather than in the onset
      of traditional pro-inflammatory reactions. The notion that astrocyte TLR may thus
      play a role not only in host defense but also in tissue repair responses prompted
      us to examine the possibility that endogenous TLR agonists could be expressed in
      the human central nervous system to regulate the apparently dual astrocyte
      functions during trauma or inflammation. As a potential source of endogenous
      agonists, a cDNA library derived from several human brain tumor cell lines was
      used. Gene pools of this library were transfected into COS-7 cells and the
      expression products were screened for their ability to induce TLR activation in
      human primary astrocytes. The screening resulted in the identification of soluble
      CD14. By using a panel of TLR-transfected HEK293 cells, we found that signaling
      by soluble CD14 was TLR2 dependent. Moreover, the CD14-triggered TLR2-mediated
      response in astrocytes lead to the production of CXCL8, IL-6, and IL12p40,
      whereas typical TLR-induced pro-inflammatory cytokines, like TNF-alpha and IL
      1beta, were not produced at detectable levels. In conclusion, our data indicate
      that apart from its well-known ability to act as a co-receptor for TLR-dependent
      signaling by peptidoglycans or LPS, soluble CD14 can also act as a direct agonist
      for TLR2.

PMID- 17205553
TI  - Trends and experiences in liver retransplantation over 15 years.
AB  - Compared to primary liver transplantation (LT), the inferior results in the
      outcome of liver retransplantation (re-LT) continue to be a major challenge. The
      purpose of this study was to analyze changes in and outcomes of re-LT over a
      period of 15 years at the Charite Virchow Clinic. Between 1989 and 2003, we
      performed 1,619 LTs and 157 re-LTs (9.7%) in 1,462 patients. A total of 119
      retransplants (50 females, 69 males) were analyzed after consideration of
      exclusion criteria: recipient age <16 years, second re-LT, primary LT as split
      liver or living-related LT, or combination with renal transplantation or Whipple
      operation. All patients received a whole-size organ. Mean follow-up was 62 months
      (6 days to 187 months). The main indications for re-LT were initial nonfunction
      (26.9%), recurrence of viral-induced hepatitis (20.2%), or acute and chronic
      rejection or thrombosis of the hepatic artery (both 16.8%). The main causes of
      death were bacterial infections (26.0%) as well as bleeding complications or
      recurrence of disease (both 16.0%) within the first postoperative month. Overall,
      50 out of 119 patients (42%) died after re-LT, 26 patients within the first 3
      months and 38 within 1 year. Overall patient survival was 89.9% after 1 month,
      78.2% after 1 year, and 67.1% after 5 years. In conclusion, our study showed good
      clinical results after re-LT. Apart from the changing indications for re-LT with
      an increasing amount of initial organ failure and hepatic artery thrombosis, the
      analysis also showed a decreasing amount of complications such as rejection,
      ischemic type biliary lesions, and recurrence of the disease with unchanged
      outcome over a period of 15 years.

PMID- 17205554
TI  - Tendons and ligaments are anatomically distinct but overlap in molecular and
      morphological features--a comparative study in an ovine model.
AB  - Tendons and ligaments are similar in composition but differ in function. Simple
      anatomical definitions do not reflect the fact individual tendons and ligaments
      have unique properties due to their adaptation to a specific role. The patellar
      tendon is a structure of particular clinical interest. A null hypothesis was
      declared stating that the patellar tendon is not significantly different in terms
      of matrix composition and collagen fibril diameter to other tendons. The lateral
      and medial collateral ligaments (LCL, MCL), anterior and posterior cruciate
      ligaments (ACL, PCL), together with the long digital extensor, superficial
      digital extensor, and patellar tendons (LDET, SDFT, PT) were harvested from three
      cadaveric ovine hindlimbs. The extracellular matrix was assessed in terms of
      water, collagen, and total sulphated glycosaminoglycan (GAG) content. The
      organization of the collagen component was determined by an ultrastructural
      analysis of collagen fibril diameter distributions, together with values for the
      collagen fibril index (CFI) and mass-average diameter (MAD). There were
      significant differences between ligaments and tendons. The PT had a bimodal
      collagen fibril diameter distribution with CFI 72.9%, MAD 202 nm, water content
      53.1%, GAG content 2.3 microg/mg, and collagen content 73.7%, which was not
      significantly different from the other tendons. The results of this study support
      the null hypothesis suggesting that the patellar tendon is similar to other
      tendons and demonstrate that tendons have different characteristics to ligaments.

PMID- 17205555
TI  - Alendronate prevents bone loss and improves tendon-to-bone repair strength in a
      canine model.
AB  - Previously we showed a loss of bone and a concomitant decrease in mechanical
      properties in the first 21 days after flexor tendon insertion site injury and
      repair in a canine model. The goal of this short-term study was to suppress bone
      loss after insertion site repair using alendronate in an attempt to prevent the
      reduction in biomechanical properties. Flexor tendons of the second and fifth
      digits of the right forelimbs of canines were injured and repaired. Dogs received
      a daily oral dose of alendronate (2 mg/kg). One digit in each dog also received a
      local dose of alendronate in the bone tunnel at the time of surgery. The repair
      was evaluated for bone mineral density (BMD) and biomechanical properties and
      compared to data from a previous study in which no alendronate was used.
      Alendronate was effective in protecting the distal phalanx from resorption during
      tendon-to-bone healing (BMD was 94 and 104% of control for systemic alendronate
      and for systemic plus local alendronate, respectively). Alendronate treatment
      prevented much of the decrease in ultimate load that occurs in the first 21 days.
      Without treatment, ultimate load was 42% of control. With systemic alendronate
      treatment and systemic plus local alendronate treatment, ultimate load was 78 and
      69% of control, respectively. Failure mode was significantly different when
      comparing alendronate treatment to repair alone. A lower incidence of suture pull
      through was found in alendronate treated dogs, suggesting less tendon
      degeneration. Ultimate load can be improved in association with preventing the
      bone loss that normally occurs during the early period following tendon-to-bone
      repair. These initial short-term data demonstrate the potential for a clinical
      treatment that could enhance tendon-to-bone healing.

PMID- 17205556
TI  - In healthy subjects without knee osteoarthritis, the peak knee adduction moment
      influences the acute effect of shoe interventions designed to reduce medial
      compartment knee load.
AB  - The purpose of this study was to evaluate shoe sole material stiffness changes
      and angle changes that are intended to reduce the peak knee adduction moment
      during walking. Fourteen physically active adults were tested wearing their
      personal shoes (control) and five intervention pairs, two with stiffness
      variations, two with angle variations, and a placebo shoe. The intervention shoes
      were evaluated based on how much they reduced the peak knee adduction moment
      compared to the control shoe. An ANOVA test was used to detect differences
      between interventions. Linear regression analysis was used to determine a
      relationship between the magnitude of the knee adduction moment prior to
      intervention and the effectiveness of the intervention in reducing the peak knee
      adduction moment. Peak knee adduction moments were reduced for the altered
      stiffness and altered angle shoes (p < 0.010), but not for the placebo shoe (p =
      0.363). Additionally, linear regression analysis showed that subjects with higher
      knee adduction moments prior to intervention had larger reductions in the peak
      knee adduction moment (p < 0.010). These results demonstrate that shoe sole
      stiffness and angle interventions can be used to reduce the peak knee adduction
      moment and that subjects with initially higher peak knee adduction moments have
      higher reductions in their peak knee adduction moments.

PMID- 17205558
TI  - Early histologic changes in fibrosing cholestatic hepatitis C.
AB  - Recurrent hepatitis C (RHCV) after liver transplantation is almost universal, and
      occasional patients will have an aggressive course characterized histologically
      by pericellular/sinusoidal fibrosis and cholestasis, known as fibrosing
      cholestatic hepatitis (FCH). The early stages and evolution of this disease have
      not been well characterized. A total of 77 liver biopsies performed for
      indication (nonprotocol) were evaluated for necroinflammation, rejection,
      cholestasis, and fibrosis. Control groups were composed of protocol biopsies from
      HCV transplant patients (10 biopsies) as well as non-HCV transplant patients (6
      biopsies). Scoring for necroinflammation, rejection, and fibrosis were compiled
      using standard criteria (hepatic activity index, Banff, Ishak, METAVIR).
      Pericellular fibrosis was staged with a novel "sinusoidal" system. A cholestasis
      scoring system was developed to quantitate parenchymal and portal features of
      cholestasis. Biopsies were categorized as rejection, RHCV, FCH, and stable based
      on histology and clinical information. FCH was found to have a higher fibrosis
      stage overall when compared to most diagnostic groups, regardless of the staging
      system used. Additionally, sinusoidal fibrosis was significantly higher in the
      FCH diagnosis group. Cholestasis was more prominent in biopsies of FCH in all
      comparisons. In conclusion, the presence of cholestasis and fibrosis with mild to
      moderate RHCV should raise the suspicion of FCH. When studying the evolution of
      these cases, the first abnormality to appear is RHCV and cholestasis, fibrosis
      develops soon after, and both continue to worsen until the point of allograft
      failure or patient death.

PMID- 17205557
TI  - Local application of recombinant human fibroblast growth factor-2 on bone repair:
      a dose-escalation prospective trial on patients with osteotomy.
AB  - Based on preclinical evidence in animal models, the present study examined the
      clinical efficacy and safety of recombinant human fibroblast growth factor-2
      (rhFGF-2) to accelerate bone repair in a dose-escalation prospective trial. One
      of three dosages (200, 400 or 800 microg) of rhFGF-2 in a biodegradable gelatin
      hydrogel was injected during surgery into the osteotomy site of 59 knee
      osteoarthritis patients undergoing high tibial osteotomy, and 57 of them were
      monitored for 16 weeks. The rhFGF-2 dose dependently increased the percentage of
      patients with radiographic bone union, and decreased the average time needed for
      such union. The percentages of patients with an absence of pain and full-weight
      bearing were also greater in the higher dosage groups than in the low dosage
      group, especially in the clinically critical periods 6, 8, and 10 weeks. Neither
      blood chemistries nor clinical adverse events were associated with the rhFGF-2
      dosages. We therefore conclude that the rhFGF-2 in gelatin hydrogel dose
      dependently accelerated radiographic bone union of a surgical osteotomy with a
      safety profile at least at the dosages used, suggesting the clinical efficacy of
      this agent for bone repair.

PMID- 17205559
TI  - Kinetics of polymethylmethacrylate particle-induced inhibition of osteoprogenitor
      differentiation and proliferation.
AB  - Periprosthetic bone loss induced by implant wear debris may be a combined effect
      of osteolysis and reduced bone formation resulting from particle-induced
      suppression of osteoprogenitor differentiation. This study investigated the time
      dependent effects of polymethylmethacrylate (PMMA) particles on the osteogenic
      capability of bone marrow osteoprogenitor cells during the early phase of
      differentiation. Murine bone marrow cells were challenged with PMMA particles
      (0.30% v/v) on the first day of growth in osteogenic medium. Particles were
      removed from culture after 1, 3, and 5 days, respectively, after which cell
      growth in osteogenic medium was continued until the 15th day. Bone marrow
      osteoprogenitor cells exposed to particles during the first 5 days of
      differentiation showed complete, irreversible inhibition of proliferation,
      alkaline phosphatase expression, and mineralization. Osteoprogenitors exposed to
      particles for more than 5 days showed the same degree of inhibition, while those
      exposed to particles for less than 5 days showed a diminished inhibitory
      response. Conditioned medium from particle-treated cells did not suppress
      osteogenic development, demonstrating that suppression of osteogenesis was not
      due to secreted inhibitory factors. This study has shown that the early phase of
      osteoprogenitor differentiation is a crucial time period during which exposure to
      PMMA particles causes irreversible inhibition of osteogenesis.

PMID- 17205560
TI  - Comparison of the stability of various internal fixators used in the treatment of
      osteochondritis dissecans--a mechanical model.
AB  - The purpose of this study was to determine what characteristics of fixation
      devices used in the treatment of osteochondritis dissecans (OCD) contribute to
      improved stability to resist shear loading. An OCD model was designed using rigid
      polyurethane foam. Each specimen consisted of two components, an osteochondral
      fragment and a corresponding defect. A total of 40 specimens were prepared and
      assigned to one of four groups: control (no extrinsic stabilizer); two 2-mm
      diameter Kirschner wires (K-wires), 40 mm in length; one threaded washer and a 28
      mm screw; and one threaded washer and a 38 mm screw. Each specimen was mounted
      onto an Iosipescu shear test fixture and subjected to shear loads at a pseudo
      static displacement rate of 0.075 mm/s. All groups demonstrated some stability;
      controls were significantly less stable than all other groups. The group with the
      threaded washer and 38-mm screw demonstrated the greatest stability (p < 0.001),
      and no difference was noted between the K-wire and 28-mm screw groups. These
      results suggest that, in this OCD model, friction conferred some intrinsic
      stability to resist loads in shear. However, stability was improved with the use
      of long implants that compressed the fragments together.

PMID- 17205561
TI  - Cost-effectiveness of screening for hepatopulmonary syndrome in liver transplant
      candidates.
AB  - The hepatopulmonary syndrome (HPS) is present in 15-20% of patients with
      cirrhosis undergoing orthotopic liver transplantation (OLT) evaluation. Both
      preoperative and post-OLT mortality is increased in HPS patients particularly
      when hypoxemia is severe. Screening for HPS could enhance detection of OLT
      candidates with sufficient hypoxemia to merit higher priority for transplant and
      thereby decrease mortality. However, the cost-effectiveness of such an approach
      has not been assessed. Our objective was to perform a cost-effectiveness analysis
      from a third-party payer's perspective of screening for HPS in liver OLT
      candidates. The costs and outcomes of 3 different strategies were compared: (1)
      no screening, (2) screening patients with a validated dyspnea questionnaire, and
      (3) screening all patients with pulse oximetry. Arterial blood gas analyses and
      contrast echocardiography were performed in patients with dyspnea or a pulse
      oximetry (SpO(2)) < or =97% to define the presence of HPS. A Markov model was
      constructed simulating the natural history of cirrhosis in a cohort of patients
      50 years old over a time horizon of their remaining life expectancy. Transition
      probabilities were obtained from published data available through Medline and
      U.S. vital statistics. Costs represented Medicare reimbursement data at our
      institution. Costs and health effects were discounted at a 3% annual rate. No
      screening was associated with a total cost of 291,898 dollars and a life
      expectancy of 11.131 years. Screening with pulse oximetry was associated with a
      cost of 299,719 dollars and a life expectancy of 12.27 years. Screening patients
      with the dyspnea-fatigue index was associated with a cost and life expectancy of
      300,278 dollars and 12.28 years, respectively. The incremental cost-effectiveness
      ratio of screening with pulse oximetry (compared to no screening) was 6,867
      dollars per life year gained, whereas that of the dyspnea-fatigue index (compared
      to pulse oximetry) was 55,900 dollars per life year gained. The cost
      effectiveness of screening depended on the prevalence and severity of HPS, and
      the choice of screening strategy was dependent on the sensitivity of the
      screening modality. In conclusion, screening for HPS, especially with pulse
      oximetry, is a cost-effective strategy that improves survival in transplant
      candidates predominantly by targeting the transplant to the subgroup of patients
      most likely to benefit. The utility of screening depends on the prevalence and
      severity of HPS in the target population.

PMID- 17205562
TI  - Investigating the possibility of cellular seeding onto an allograft scaffold for
      impaction grafting in revision arthroplasty.

PMID- 17205563
TI  - Long-term survival and predictors of relapse after orthotopic liver
      transplantation for alcoholic liver disease.
AB  - The relevance of sobriety for outcome after orthotopic liver transplantation
      (OLT) for alcoholic liver disease (ALD) is still discussed controversially. We
      conducted a retrospective analysis of 300 patients transplanted for ALD with
      regard to recurrent alcohol consumption, risk factors for drinking after OLT, and
      long-term survival. The 300 patients underwent OLT for ALD between 1989 and 2002.
      Median follow-up was 89 months. Incidence and severity of drinking, survival
      rates, and causes of death were assessed. Age, gender, duration of pretransplant
      sobriety, social support, presence of children, and the results of psychosomatic
      evaluation were analyzed for their impact on recurrent alcohol consumption after
      OLT. Drinking of various degrees was observed in 19% of ALD patients after OLT.
      Pretransplant sobriety of less than 6 months, absence of companion in life,
      presence of young children, and a predicted poor psychosomatic prognosis were
      associated with an increased risk of recurrent alcohol consumption, whereas age
      and gender were not independent risk factors. Survival rates of patients who
      resumed abusive drinking were significantly lower than survival rates of
      abstinent patients or patients with minor lapses. Recurrent alcoholic liver
      disease accounted for the vast majority of deaths among patients who resumed
      abusive drinking after OLT, whereas malignant tumors, infections, and
      cardiovascular disease were the most common causes of death among abstinent
      patients. In conclusion, abusive drinking after OLT is associated with poor long
      term survival. Analysis of risk factors may help to identify patients with a high
      risk for recurrent alcohol abuse after OLT.

PMID- 17205564
TI  - Genes with greater up-regulation in the fracture callus of older rats with
      delayed healing.
AB  - The rate of bone formation to bridge a fracture gap slows with age. To explore
      potential pathogenic mechanisms and possible negative-feedback responses by the
      skeleton to this reduced rate of healing, mRNA transcripts up-regulated more
      and/or longer were studied in older rats with delayed healing. Female rats at 6
      (young), 26 (adult), and 52 (old) weeks of age received unilateral diaphyseal
      femoral fractures with intramedullary rod stabilization. At 0, 0.4, 1, 2, 4, and
      6 weeks after fracture, the fracture site was harvested. Total RNA was extracted,
      cRNA was prepared, and the cRNA was hybridized to 54 Affymetrix U34A microarrays
      (three arrays/age/time point). Transcripts for 180 genes were identified as up
      regulated more and/or longer in old rats with delayed fracture healing. Of these,
      60 were selected for more intense review. Significantly more and/or longer
      expression was seen in genes related to myofibroblasts, cell proliferation,
      calcification inhibition, TGF-beta activity, lipid metabolism, cell adhesion, and
      the cytoskeleton. Further study is needed to determine if these up-regulated
      transcripts are related to the pathological processes which slow healing or are
      related to attempts by the fracture tissue to stimulate bone to bridge the
      fracture gap.

PMID- 17205565
TI  - Cell division of Giardia intestinalis: assembly and disassembly of the adhesive
      disc, and the cytokinesis.
AB  - Trophozoites of Giardia are equipped with a special organelle of attachment,
      essential for parasite survival and pathogenicity, the ventral disc. Although its
      basic structure is well established, its reorganization and assembly during cell
      replication is poorly understood. We addressed some of these problems with aid of
      conventional, confocal and electron microscopy. We found that dividing Giardia
      alternates attached and free swimming phases in accordance with functional
      competence of the parent or newly assembled discs. The division started in
      attached cells by detachment of the disc microtubules from basal bodies.
      Shortening and eventual loss of the giardin microribbons, and unfolding of the
      microtubular layer resulting in collapse of the disc chamber and parasite
      detachment underlined gradual disassembly of the parent disc skeleton. Two
      daughter discs assembled on the dorsal side of the attached cell, with their
      ventral sides exposed on the parent cell surface and their microtubular skeletons
      growing in counter-clockwise direction. A depression between the assembling discs
      marked the cleavage plane. The splitting continued during the free-swimming phase
      with ventral-ventral axial symmetry in a plane of the daughter discs. Finally,
      the daughter cells with fully developed discs but still connected tail to tail by
      a cytoplasmic bridge, attached to a substrate and terminated the division by a
      process resembling adhesion-dependent cytokinesis. The mode of assembly of the
      daughter discs and plane of the division is compatible with maintenance of the
      left-right asymmetry of the Giardia cytoskeleton in progeny, which cannot be
      satisfactorily explained by alternative models proposed so far.

PMID- 17205566
TI  - Stress analysis of the anterior tibial post in posterior stabilized knee
      prostheses.
AB  - Recent retrieval studies have indicated a high incidence of polyethylene wear on
      the anterior tibial post caused by impingement. This study investigated the
      influences of post-cam design features and component alignment on the stress
      distribution in the anterior tibial post when subjected to the impingement
      loading. Two three-dimensional finite element models of posterior stabilized knee
      prostheses were constructed, one with flat on flat (FF) and another with curve on
      curve (CC) contact surfaces between anterior tibial post and femoral cam. The
      polyethylene insert was modeled with elastoplastic properties. Nine cases, three
      hyperextension angles (0 degrees , 5 degrees , and 10 degrees ) combined with
      three axial tibial rotations (0 degrees , 2.5 degrees , and 5 degrees )
      simulating different component alignments were analyzed. A vertical compressive
      load of 2,000 N and an extension moment of 45 Nm were applied simultaneously. The
      FF model had larger stress increases than the CC model in both hyperextension and
      tibial rotation compared with the neutral position. The maximum increase for the
      FF model was 68% in peak contact stress, 125% in von Mises stress, and 58% in
      tensile stress in the extreme case of 10 degrees of hyperextension combined with
      5 degrees of axial rotation. Stress concentration was found at the anterior
      corner of the post in the FF model; this was not found in the CC model. The curve
      on curve design can reduce edge loading on the tibial post, especially during
      axial tibiofemoral rotation.

PMID- 17205567
TI  - Anti-catabolic effect of OP-1 in chronically compressed intervertebral discs.
AB  - Experimental animal models of disc degeneration have been used to assess the
      biomechanical behavior, biochemical composition, and biological changes in the
      intervertebral discs. The objective of our study was to evaluate the anabolic and
      anti-catabolic effects of intradiscal injection of Osteogenic Protein-1 (OP-1) by
      histology and immunohistochemistry in disc degeneration model. Thirty-four rats
      were divided into five groups: intact control; sham control; compressed nucleus
      pulposus (NP) injected with saline; and two OP-1 groups: COP-1 group (compression
      was continued after intradiscal OP-1 injection) and ROP-1 group (compression was
      released at the time of OP-1 injection). Anabolic and anti-catabolic effects of
      OP-1 were evaluated by histology and immunohistochemistry with the following
      antibodies: anti-pro- and anti-mature OP-1, anti-MMP-13, anti-aggrecanase, anti
      substance P, anti-tumor necrosis factor-alpha (TNF-alpha), and anti-interleukin
      1beta (IL-1beta). The OP-1 injection to the degenerative disc stimulated an
      anabolic response characterized by the restoration of the normal morphology of
      the disc, increased Safranin O staining in the NP, extention of the extracellular
      matrix, and stimulation of endogenous OP-1 synthesis in the NP, annulus fibrosis
      (AF), and end-plate. The anti-catabolic effect of OP-1 was documented by reduced
      immunostaining for aggrecanase, MMP-13, substance P, TNF-alpha, and IL-1beta.
      This study confirmed the anti-catabolic activity of OP-1 as demonstrated
      previously in human articular cartilage and provided critical evidence for the
      potential of OP-1 therapy in the treatment of disc degeneration. Because
      substance P is a neuropeptide linked with inflammation and pain, a reduction in
      the level of this protein may support our previously reported results on the
      effect of OP-1 on pain-related behavior.

PMID- 17205568
TI  - Application of immunomagnetic cell enrichment in combination with RT-PCR for the
      detection of rare circulating head and neck tumor cells in human peripheral
      blood.
AB  - Detection of rare, circulating tumor cells (CTC's) in human peripheral blood is a
      potential indicator of prognosis and diagnosis in oncology. Typical methods to
      detect these CTC's are either by immunocytochemistry (ICCS) or RT-PCR. However
      without accurate, rapid, and reproducible enrichment processes, these detection
      techniques are labor intensive and/or unreliable. In this article, a repeatable
      enrichment process that included a flow-through immunomagnetic cell separation
      system, the quadrupole magnetic sorter (QMS) was optimized with the aid of a
      statistical analysis software package. The QMS was operated in a negative mode of
      operation by immunomagnetically targeting normal human peripheral blood
      lymphocytes (PBL) through the CD45 surface marker. Three head and neck squamous
      carcinoma cell lines (HNSCC), Detroit-562, SCC-4, and CAL-27, were used to
      determine the sensitivity of RT-PCR for the epidermal growth factor receptor
      (EGFR) in spiked PBL. The detection purity needed for detection was found to be
      one cell in 10(4), one cell in 10(3), and one cell in 10(5) for the Detroit-562,
      SCC-4, and CAL-27, respectively. The actual number of cancer cells needed for RT
      PCR detection ranged from 30 to 1 cell. To mimic the potential concentration of
      rare CTC present in peripheral blood of cancer patients, the spiking
      concentration was chosen to be one cancer cell per 10(5) total leukocytes from
      healthy donors. Using a single step immunomagnetic labeling, the final, optimized
      enrichment process produced a 57.6 +/- 30.3-fold (n = 6) enrichment of the rare
      cancer cells with a final cancer cell recovery of (77.8 +/- 6.6)%.

PMID- 17205570
TI  - Flow cytometry PRA using lymphocyte pools from random donors.
AB  - BACKGROUND: Pools of lymphocytes from carefully chosen donors have been used for
      flow cytometry (FC) panel reactive antibody (PRA) assays. We intended to devise
      an FC PRA assay using mixed lymphocyte pools from a large number of randomly
      selected donors (RD FC PRA) to accurately predict the likelihood of a positive
      HLA crossmatch. METHODS: Lymphocyte pools were prepared from randomly selected
      donors (N = 120). %PRA was calculated based on the anti-IgG FITC histogram of the
      T cells. The proposed RD FC PRA assay was assessed in comparison with the bead FC
      PRA, antiglobulin-augmented CDC (AHG-CDC) PRA assay, and the expected %PRA
      calculated by summing up the antigen frequencies of the known specificities.
      RESULTS: In 29 FC crossmatch positive sera, the positivity rate for the bead FC,
      RD FC, and AHG-CDC PRA was 100, 100, and 79%, and the mean %PRA was 77% +/-
      0.205). In 19 sensitized patients with a negative FC crossmatch, the positivity
      rate was 21% using the RD FC PRA and 16% using the bead FC PRA, which suggested
      that both assays had similar abilities to detect low levels of HLA antibodies.
      CONCLUSIONS: The RD FC PRA assay allows easy panel preparation, reduces cost, and
      naturally reflects the probabilities of a positive crossmatch in the population
      to which the cadaveric donor belongs. Therefore, this new assay is expected to be
      useful as another approach to determine the % PRA.

PMID- 17205569
TI  - Assessing immunophenotyping performance: proficiency-validation for adopting
      improved flow cytometry methods.
AB  - BACKGROUND: The continuous improvement and evolution of immune cell phenotyping
      requires periodic upgrading of laboratory methods and technology. Flow cytometry
      laboratories that are participating in research protocols sponsored by the NIAID
      are required to perform "switch" studies to validate performance before methods
      for T-cell subset analysis can be changed. METHODS: Switch studies were conducted
      among the four flow cytometry laboratories of the Multicenter AIDS Cohort Study
      (MACS), comparing a 2-color, lyse-wash method and a newer, 3-color, lyse no-wash
      method. Two of the laboratories twice failed to satisfy the criteria for
      acceptable differences from the previous method. Rather than repeating more
      switch studies, these laboratories were allowed to adopt the 3-color, lyse no
      wash method. To evaluate the impact of the switch to the new method at these two
      sites, their results with the new method were evaluated within the context of all
      laboratories participating in the NIH-NIAID-Division of AIDS Immunology Quality
      Assurance (IQA) proficiency-testing program. RESULTS: Laboratory performance at
      these two sites substantially improved relative to the IQA standard test results.
      Variation across the four MACS sites and across replicate samples was also
      reduced. CONCLUSIONS: Although switch studies are the conventional method for
      assessing comparability of laboratory methods, two alternatives to the
      requirement of repeating failed switch studies should be considered: (1) test the
      new method and assess performance on the proficiency testing reference panel, and
      (2) prior to adoption of the new methods, use both the old and the new method on
      the reference panel samples and demonstrate that performance with the new method
      is better according to standard statistical procedures. These alternatives may
      help some laboratories' transition to a new and superior methodology more quickly
      than if they are required to attempt multiple, serial switch studies.

PMID- 17205571
TI  - Human papillomavirus-related cellular changes measured by cytometric analysis of
      DNA ploidy and chromatin texture.
AB  - BACKGROUND: Image cytometry has provided two highly sensitive markers for the
      identification of the malignant potential of squamous lesions. Aneuploidy and
      chromatin texture have been investigated as quantitative measures of nuclear
      damage in premalignant lesions and carcinoma. Real-time PCR methods have evolved
      to yield highly specific measurements of mRNA expression in very sparse cellular
      samples. METHODS: Human papillomavirus (HPV) 16 and 18 E7 mRNA expression was
      measured using quantitative RT-PCR. DNA index and chromatin measures were taken
      from image cytology samples. The chromatin features, through discriminant
      analysis, were aggregated into a score, and both measurements were related to
      mRNA expression. RESULTS: mRNA level and DNA index show an increasing trend over
      increasing histological grades. However, DNA index and chromatin score were not
      correlated to mRNA levels in these samples. Chromatin score differed by mRNA type
      found with HPV 18 infected samples having a higher score than those with HPV 16.
      Samples infected with HPV 16 and HPV 18 had even higher chromatin scores.
      CONCLUSIONS: DNA index and chromatin score were not directly correlated with mRNA
      levels. However both mRNA and DNA index were related to histological grade, and
      chromatin score was associated with HPV type. Therefore, DNA index and mRNA
      levels could be independent predictors of cervical dysplasia, and chromatin score
      could be related to the viral integration process in cells infected with HPV 18
      or dual infections.

PMID- 17205572
TI  - The distal lateral arm flap for resurfacing of extensive defects of the digits.
AB  - The distal lateral arm flap (DLAF) was used to reconstruct six extensive defects
      of the digits: 2 degloving injuries of the thumb and 4 major skin losses of the
      fingers. Two adjacent fingers were involved in 1 patient. Flap size ranged from 3
      x 7 cm to 9 x 14 cm. Four flaps were reinnervated using the posterior cutaneous
      nerve of the forearm. All flaps survived, though 1 showed marginal necrosis.
      Average follow-up was 53.4 months. Thumb opposition scored 5 according to
      Kapandji; finger ROM averaged 50.75%; pinch strength 72.5%. Protective sensation
      with touch localization was restored. Patient satisfaction for resurfaced digits
      averaged 8.9 on a 10-points visual analogic scale. All donor sites resulted in a
      painless scar with good patient satisfaction. The DLAF offers a thin, pliable
      skin ideal for digit reconstruction, with low rate of donor site morbidity and
      can be considered when toe-to-hand flap transfer is not advisable or refused by
      the patient.

PMID- 17205573
TI  - Composite reconstruction in advanced cancer of the mouth floor: autogenous frozen
      thawed mandibular bone and free flaps.
AB  - Mandibular symphyseal resection requires composite reconstructions, often with
      unsatisfactory morphofunctional results. Seven patients with advanced squamous
      cell carcinoma of the floor of the mouth underwent block resection with immediate
      reconstruction, using the removed mandible treated with liquid nitrogen and
      covered with a free forearm flap. In all cases, the resection was radical and no
      major postoperative complications occurred. Two patients died in 6 months for
      distant metastases and regional recurrence. In the other 5 patients, no local
      recurrence occurred at a mean follow-up of 52 months (36-70). Immediate cosmetic
      and functional results were good. Of the 5 patients, 4 had late complications
      requiring further surgery. This technique of bone reimplantation produces no
      donor site morbidity, perfect immediate morphological result, and is of low cost.
      The free forearm flap is effective in sealing the oral cavity, though further
      clinical and experimental studies are necessary to reduce late local
      complications.

PMID- 17205574
TI  - Ulnar nerve repair by end-to-side neurorrhaphy on the median nerve with
      interposition of a vein: an experimental study.
AB  - Our study used a rat animal model to verify that Schwann cell migration,
      collateral axonal sprouting, and regeneration were not hindered by interposition
      of a 10-mm vein segment between the distal stump of the transected ulnar nerve
      and the donor median nerve in end-to-side reconstruction. Reconstructed nerves
      were withdrawn at 7, 14, 30, and 60 days after surgery, then analyzed by confocal
      laser microscopy after immunolabeling with anti-neurofilament-200 kD (an axonal
      marker) and anti-S100 (a glial marker) antibodies. Results are reported at 7, 14,
      30, and 60 days after surgery. Our observations indicate that chemotactic factors
      that stimulate end-to-side nerve regeneration can exert their action at this
      distance. These findings suggest a possible clinical application for this
      surgical technique in cases when the severed nerve stump is far from the
      potential donor nerve.

PMID- 17205575
TI  - Introduction: reconstructive microsurgery in Italy.

PMID- 17205576
TI  - Clinical evaluation of a hyaluronan-based gel following microsurgical
      reconstruction of peripheral nerves of the hand.
AB  - A controlled clinical trial was performed to investigate the safety and efficacy
      of the hyaluronate-based gel polymer Hyaloglide after microsurgical
      reconstruction of peripheral nerves of the hand. Thirty patients were randomized
      to receive either no postsurgical treatment (n = 16) or Hyaloglide (n = 14) and
      were clinically evaluated at various intervals for 1 year. The application of
      Hyaloglide posed no safety concerns. Efficacy was assessed by the recovery of
      sensitivity, measurement of pain, and progression of Tinel's sign. The Hyaloglide
      treated group showed better improvement in recovery from pain, approaching
      statistical significance during the first 3 months postsurgery. Likewise,
      recovery of sensitivity was also higher in the Hyaloglide-treated group
      throughout the entire follow-up period, and the distance of Tinel's sign was
      longer in the Hyaloglide-treated group (P < 0.05 at day 30). The application of
      Hyaloglide may improve recovery of sensitivity and decrease pain following
      microsurgical repair of the peripheral nerves of the hand.

PMID- 17205577
TI  - Origin and history of end-to-side neurorrhaphy.
AB  - This historical note offers a perspective concerning the origin of the employment
      of end-to-side (termino-lateral) anastomosis for nerve repair and summarizes the
      works that have been published on this surgical technique through the first part
      of the 20th Century. While the origin of end-to-side neurorrhaphy is usually
      dated to the beginning of the 20th Century, some works referring to this
      technique were published earlier, the first of which dates as far back as 1873. A
      number of interesting clinical and experimental studies have been carried out on
      end-to-side nerve anastomosis during the first years of the twentieth century.
      However, this literature is not easily detectable through current online
      scientific databases. In this paper we will give an overview of these early
      works. This history contributes interesting information to the debate surrounding
      this surgical concept and adds perspective to the use of a technique that has
      attracted a great deal of attention over the last 15 years.

PMID- 17205578
TI  - The versatility of vascularized iliac crest with internal oblique muscle flap for
      composite upper maxillary reconstruction.
AB  - The middle third defects of the face following total or partial oncologic
      maxillectomy include very important facial structures, both for esthetical and
      for functional reasons. Among the outcomes, large oronasal or oromaxillary
      fistulas due to destruction of big bone segments and soft tissues have long been
      the consequences of such extensive surgical ablations. In the last few years,
      immediate reconstruction of maxillary bones and soft tissues has proved to be a
      reliable morphofunctional reconstruction technique following surgery for large
      oncological defects or the late effects of radiation therapy. Among other free
      flaps such as composite fibula, composite scapula, or composite radial, the use
      of vascularized iliac crest with the internal oblique flap has become our flap
      choice for morphofunctional maxillary reconstruction for bone segments within 6
      15 cm of length, and when there is no need for overlying facial skin or oral
      sphincter reconstruction. The advantages of this composite bone flap are its
      available large and resizable bone stock; the quality of the bone for transfer
      (optimal height, depth, and contour to maintain a good facial profile); and the
      possibility to properly reconstruct the oral lining, orbital content; and
      maxillary soft tissues with a portion of the internal oblique muscle flap raised
      with the same pedicle. In addition, this flap's soft tissue will epithelialize
      during the healing stages.

PMID- 17205579
TI  - Atypical reconstructions with free jejunum flap after circumferential
      pharyngolaryngectomy.
AB  - The ideal reconstruction after circumferential pharyngolaryngectomy is
      represented by the jejunum free flap, but when the resection extends to the oro-
      or nasopharynx, the discrepancy between the lumen of the flap and the pharyngeal
      defect represents a disadvantage. Two reconstructions to overcome this problem
      are presented: end-to-side anastomosis between the pharynx and the antimesenteric
      side of the jejunum; and a jejunal "reservoir." The type 1 technique is quicker
      to perform, but can result in dysphagia; the type 2 technique is more complex,
      but usually no dysphagia is observed. In our opinion, no ideal surgical technique
      exists to equal the jejunum loop. The choice must be tailored to the single
      patient, bearing in mind the degree of the defect, the stage of the tumor
      removed, the general conditions of the patient, and personal surgical experience.
      Whatever procedure is chosen, it should provide the best possible quality of life
      for the expected life span of the patient.

PMID- 17205580
TI  - The expression pattern of nuclear receptors during cerebellar development.
AB  - The cerebellum is essential for fine control of movement and posture, and it has
      been a useful model for studying many aspects of neural development because of
      its relatively simple anatomy and developmental program. However, the roles of
      nuclear receptors (NRs) underlying formation of the cerebellum and maintenance of
      cerebellar functions are still poorly characterized. As a contribution to the
      Nuclear Receptor Signaling Atlas (NURSA), we employed immunohistochemistry to
      investigate the expression pattern of 18 NRs in the cerebellum. Ten receptors
      were demonstrated to be expressed in the postnatal day 21 (P21) cerebellum. Among
      them, five receptors (COUP-TFI, COUP-TFII, RORalpha, ERbeta, and ERRgamma) were
      expressed at all stages (embryonic stage, P0, P7, and P21) examined.
      Interestingly, COUP-TFI and COUP-TFII show differential anterior-posterior
      expression patterns during cerebellar development. Taken together, our results
      suggest that members of the nuclear receptor superfamily might play importantly
      physiological roles in the cerebellum.

PMID- 17205581
TI  - Socs 3 modulates the activity of the transcription factor Stat3 in mammary tissue
      and controls alveolar homeostasis.
AB  - Signal transducer and activator of transcription 5 and 3 (Stat5 and Stat3)
      control pregnancy-mediated mammary development and involution-dependent
      remodeling, respectively. Suppressor of cytokine signaling 3 (Socs3) has been
      implicated in the modulation of both Stat3 and Stat5 activity. To explore the
      biology of Socs3 in mammary tissue, the gene was deleted using Cre-mediated
      recombination. Deletion of the Socs3 gene from mammary stem or early progenitor
      cells did not grossly alter pregnancy-mediated mammary development but resulted
      in impaired lactation due to attenuated proliferation. Loss of Socs3 from
      differentiated luminal cells did not interfere with glandular function during
      lactation, but resulted in accelerated tissue remodeling upon weaning. Loss of
      Socs3 led to enhanced and precocious Stat3 activation. Thus, Socs3 serves as a
      modulator of Stat3 activity to ensure controlled proliferation and apoptosis in
      pregnancy and involution, respectively.

PMID- 17205582
TI  - Controlled rotary motion in a monolayer of molecular motors.

PMID- 17205583
TI  - Direct ortho iodination of beta- and gamma-aryl alkylamine derivatives.

PMID- 17205584
TI  - Fast high-resolution protein structure determination by using unassigned NMR
      data.

PMID- 17205586
TI  - Nanometer-sized shell molecules that confine endohedral polymerizing units.

PMID- 17205585
TI  - Site isolation and epoxidation reactivity of a templated ferrous
      bis(phenanthroline) site in porous silica.

PMID- 17205587
TI  - A mild chemically cleavable linker system for functional proteomic applications.

PMID- 17205588
TI  - Cyclopentadienyl zincates: synthesis and X-ray studies of sodium and potassium
      salts of the [Zn(C5H5)3]- and [Zn2(C5H5)5]- ions.

PMID- 17205589
TI  - Water gas shift reaction on Cu and Au nanoparticles supported on CeO2(111) and
      ZnO(0001): intrinsic activity and importance of support interactions.

PMID- 17205590
TI  - Dibenzo[c,g]fluorene: the combination of cyclopentadiene and 1,1'-binaphthyl in
      one ligand.

PMID- 17205591
TI  - Diastereomeric fluoroolefins as peptide bond mimics prepared by asymmetric
      reductive amination of alpha-fluoroenones.

PMID- 17205592
TI  - Highly controlled living radical polymerization through dual activation of
      organobismuthines.

PMID- 17205593
TI  - In vitro study of magnesium-calcite biomineralization in the skeletal materials
      of the seastar Pisaster giganteus.
AB  - The mechanisms of formation of biogenic magnesium-rich calcite remain an enigma.
      Here we present ultrastructural and compositional details of ossicles from the
      seastar Pisaster giganteus (Echinodermata, Asteroidea). Powder X-ray diffraction,
      infrared spectroscopy and elemental analyses confirm that the ossicles are
      composed of magnesium-rich calcite, whilst also containing about 0.01 % (w/w) of
      soluble organic matrix (SOM) as an intracrystalline component. Amino acid
      analysis and N-terminal sequencing revealed that this mixture of intracrystalline
      macromolecules consists predominantly of glycine-rich polypeptides. In vitro
      calcium carbonate precipitation experiments indicate that the SOM accelerates the
      conversion of amorphous calcium carbonate (ACC) into its final crystalline
      product. From this observation and from the discovery of ACC in other closely
      related taxa, it is suggested that substitution of magnesium into the calcite
      lattice through a transient precursor phase may be a universal phenomenon
      prevalent across the phylum echinodermata.

PMID- 17205594
TI  - Hydrogen-bonded dendronized polymers and their self-assembly in solution.
AB  - Frechet-type benzyl ether dendrons of second and third generations with a
      carboxyl group (G2, G3) at the apex site could attach to poly(4-vinylpyridine)
      (PVP), forming hydrogen-bonded dendronized polymers (HB denpols) in their common
      solvent, chloroform. The HB denpols show unique self-assembly behavior, forming
      vesicles in the common solvent under ultrasonic treatment. The structure and
      morphology of the vesicles were characterized by dynamic light scattering (DLS),
      static light scattering (SLS), SEM, TEM, and AFM. The size of the vesicles
      decreases and the thickness of the vascular membrane increases as the molar ratio
      of Gx/PVP increases. The hydrogen bonding, pi-pi aromatic stacking of the
      dendrons, and the considerable difference in architecture between the dendron Gx
      and PVP are the main factors facilitating the assembly of the HB denpols in the
      common solvent.

PMID- 17205595
TI  - Mechanistic study on rearrangement cascades starting from annulated 2-aza-hepta
      2,4-dienyl-6-ynyl anions: formation of aniline and azepine derivatives.
AB  - Deprotonation of benzothiophene-derived alkynyl imine 11 with lithium
      diisopropylamide (LDA) and subsequent transmetalation with ZnCl2 etherate
      furnished azepine 12 upon aqueous workup. Similarly, alkynyl benzaldimine 1a gave
      a mixture of benzazepine 13 and naphthylamine 14. Allylic benzonitriles 15 a,b
      reacted to produce naphthylamine 16 upon deprotonation with LDA at room
      temperature. In an analogous manner, imino benzonitrile 17 may be converted into
      4-amino isoquinoline 18 by means of an intramolecular nucleophilic attack on the
      nitrile function upon treatment with LDA. The allylic benzonitriles 19 a,b were
      prepared by LDA treatment of alkynyl imine 11. They were further converted to
      amino dibenzothiophene 20 by LDA deprotonation and aqueous workup. These various
      transformations represent the key steps of a multistep reaction cascade, which
      was previously postulated on the basis of quantum chemical calculations. Thus,
      all features of this complex rearrangement mechanism could now be confirmed
      experimentally. DFT calculations support the lower reactivity of zinc species in
      the ring-opening step compared to the lithium intermediates. All new compounds
      were completely characterized by spectroscopic data, including X-ray diffraction
      studies for the key compounds 12, 19 a, and 20.

PMID- 17205597
TI  - Native proteomic analysis of protein complexes in murine intestinal brush border
      membranes.
AB  - Intestinal epithelial cell protrusions referred as microvilli or brush border
      membranes (BBMs) are specialized in the digestion, uptake, and transport of
      nutrients, trace elements and vitamins from intestinal lumen into the
      circulation. Disorders of intestinal absorption are common in human pathology and
      include serious defects such as malabsorption. A detailed description of native
      digestive protein complexes in BBMs is therefore essential for understanding the
      physiology and pathology of digestion and absorption. In this study, we employed
      blue native PAGE (BN-PAGE) technique to separate protein complexes from purified
      mouse intestinal BBMs. We found 23 distinct protein complexes, which were cut off
      from the gel, and their protein composition was determined by LC-MS/MS. A total
      of 55 individual proteins were identified including peptidases, enzymes of
      carbohydrate metabolism, membrane transporters, cytoskeletal proteins,
      chaperones, and regulatory enzymes. From the identified proteins, 50% represent
      molecules with at least one predicted transmembrane domain as predicted by SOSUI
      software. To the best of our knowledge, this work is the first attempt aimed to
      characterize the native membrane proteome of intestinal BBM. As demonstrated
      here, BN-PAGE is a powerful tool for the separation of not only mitochondrial,
      but also membrane hydrophobic proteins in general. In addition, BN-PAGE technique
      preserves metal-protein interactions, as shown by the presence of 65Zn in
      metalloprotein complexes, isolated from zinc-radiolabeled BBMs.

PMID- 17205600
TI  - New mortalin and histidyl tRNA synthetase isoforms point out a pitfall in
      proteomic analysis of Egr1 genetically modified mice.
AB  - Egr1 (Zif268) is an immediate early gene encoding an inducible transcription
      factor involved in synaptic plasticity and several forms of memory in rodents.
      Using 2-DE and MS, we compared proteomes of hippocampal subregions and cortex in
      Egr1-deficient and wild-type littermates. Two significant differences were
      identified: a shift in the pI of the molecular chaperone mortalin
      (mtHsp70/PBP74/Grp75) and the apparent disappearance of histidyl tRNA synthetase
      (HisRS). We found that the pI shift for mortalin in Egr1-deficient mice was
      caused by a difference in protein sequence: D626G. Using cDNA sequencing, we
      demonstrated for both mortalin and HisRS that protein differences were not due to
      a lack of Egr1 but to DNA polymorphism between the C57Bl/6J and 129/Sv strains
      used to generate the Egr1-deficient mice. Our results show that mortalin and
      HisRS genes, which map closely to the Egr1 locus, have conserved the 129/Sv
      haplotype despite numerous back-crossing of the null mice progeny with C57Bl/6J
      animals. This demonstrates that allelic differences between mouse strains can
      introduce variations in differential proteomic analyses of genetically modified
      organisms. Finally, we report the identification of new isoforms of HisRS and
      mortalin (mot-3) encoded by the 129/Sv haplotype.

PMID- 17205601
TI  - Proteomic profiling identifies breast tumor metastasis-associated factors in an
      isogenic model.
AB  - A combination of LC and MS was applied to an isogenic breast tumor metastasis
      model to identify proteins associated with a cellular phenotype. Chromatofocusing
      followed by nonporous-RP-HPLC/ESI-TOF MS was applied to cell lysates of a pair of
      monoclonal cell lines from the human breast carcinoma cell line MDA-MB-435 that
      have different metastatic phenotypes in immune-compromised mice. This method was
      developed to separate proteins based on pI and hydrophobicity. The high
      resolution and mass accuracy of ESI-TOF measurements provided a good correlation
      of theoretical MW and experimental Mr values of intact proteins measured in mass
      maps obtained in the pH range 3.8-6.4. The isolated proteins were digested by
      trypsin and analyzed by MALDI-TOF MS, MALDI-QIT-TOF MS, and monolith-based
      HPLC/MS/MS. The unique combination of the techniques provided valuable
      information including quantitation and modification of proteins. We identified 89
      selected proteins, of which 43 were confirmed as differentially expressed.
      Metastasis-associated proteins included galectin-1, whereas annexin I and annexin
      II were associated with the nonmetastatic phenotype. In this study, we
      demonstrate that combining a variety of MS tools with a multidimensional liquid
      phase separation provides the ability to map cellular protein content, to search
      for modified proteins, and to correlate protein expression with cellular
      phenotype.

PMID- 17205602
TI  - Differential radioactive quantification of protein abundance ratios between
      benign and malignant prostate tissues: cancer association of annexin A3.
AB  - A differential quantitative protein expression study, comparing matched prostate
      cancerous and benign tissues from 31 patients, revealed proteins newly associated
      with prostate cancer. Average effects for 17 proteins whose abundance was
      significantly different (p<0.01) across patients ranged from 1.5- to 6.1-fold,
      and included a number of known cancer markers. The most differentially abundant
      proteins between cancer and benign samples were isopeptidase T, serum amyloid P
      (SAP), annexin A3 (ANXA3) and mitochondrial enoyl coenzyme-A hydratase. SAP is
      restricted to stroma in healthy tissue, and the lower abundance in tumours may be
      explained by the reduced stromal content. ANXA3 is present in healthy epithelial
      cells, exhibits strong staining in precancerous prostatic intraepithelial
      neoplasia, and is relatively less abundant in individual tumour cells of
      increasing Gleason pattern (GP), despite exhibiting higher overall tissue
      abundance in tumours. ANXA3 staining was predominantly cytoplasmic, yet nuclear
      localization was also observed. Strongly staining single cells, possibly
      phagocytes, were interspersed in highly dedifferentiated GP5 tumour areas among
      tumour cells without measurable ANXA3. Local recurrent androgen ablation therapy
      resistant tumours exhibit heterogenous low levels of ANXA3 staining. Results are
      discussed focussing on the potential implications for tumour tissues.

PMID- 17205603
TI  - Photogenerated glycan arrays identify immunogenic sugar moieties of Bacillus
      anthracis exosporium.
AB  - Using photogenerated glycan arrays, we characterized a large panel of synthetic
      carbohydrates for their antigenic reactivities with pathogen-specific antibodies.
      We discovered that rabbit IgG antibodies elicited by Bacillus anthracis spores
      specifically recognize a tetrasaccharide chain that decorates the outermost
      surfaces of the B. anthracis exosporium. Since this sugar moiety is highly
      specific for the spores of B. anthracis, it appears to be a key biomarker for
      detection of B. anthracis spores and development of novel vaccines that target
      anthrax spores.

PMID- 17205604
TI  - Detection and identification of bacterial cell surface proteins by fluorescent
      labeling.
AB  - A rapid method of detection and identification of bacterial cell surface proteins
      is needed to better understand the interaction of bacteria with host components.
      To detect cell surface proteins, we have labeled cells of the Gram-negative
      anaerobic bacterium, Porphyromonas gingivalis, with fluorescent cyanine dyes, Cy3
      and Cy5. We demonstrate that only cell surface proteins were labeled, indicating
      the method applied in our study is suitable for detection and identification of
      cell surface proteins in Gram-negative bacteria and possibly other organisms.

PMID- 17205606
TI  - A comparative proteome and phosphoproteome analysis of differentially regulated
      proteins during fertilization in the self-incompatible species Solanum chacoense
      Bitt.
AB  - We have used 2-DE for a time-course study of the changes in protein and
      phosphoprotein expression that occur immediately after fertilization in Solanum
      chacoense. The phosphorylation status of the detected proteins was determined
      with three methods: in vivo labeling, immunodetection, and phosphoprotein
      specific staining. Using a pI range of 4-7, 262 phosphorylated proteins could be
      mapped to the 619 proteins detected by Sypro Ruby staining, representing 42% of
      the total proteins. Among these phosphoproteins, antibodies detected 184 proteins
      from which 78 were also detected with either of the other two methods (42%). Pro
      Q Diamond phosphoprotein stain detected 111 proteins, of which 76 were also
      detected with either of the other two methods (68%). The 32P in vivo labeling
      method detected 90 spots from which 78 were also detected with either of other
      two methods (87%). On comparing before and after fertilization profiles, 38
      proteins and phosphoproteins presented a reproducible change in their
      accumulation profiles. Among these, 24 spots were selected and analyzed by LC
      MS/MS using a hybrid quadrupole-TOF (Q-TOF) instrument. Peptide data were
      searched against publicly available protein and EST databases, and the putative
      roles of the identified proteins in early fertilization events are discussed.

PMID- 17205607
TI  - Conifer defense against insects: proteome analysis of Sitka spruce (Picea
      sitchensis) bark induced by mechanical wounding or feeding by white pine weevils
      (Pissodes strobi).
AB  - Feeding insects can have major ecological and economic impacts on both natural
      and planted forests. Understanding the molecular and biochemical mechanisms by
      which conifers defend themselves from insect pests is a major goal of ongoing
      research in forest health genomics. In previous work, we demonstrated a complex
      system of anatomical, chemical, and transcriptome responses in Sitka spruce
      (Picea sitchensis) upon feeding by the economically significant insect pest, the
      white pine weevil (Pissodes strobi). In this study, changes to the proteome of
      Sitka spruce bark tissue were examined subsequent to feeding by white pine
      weevils or mechanical wounding. 2-D PAGE and high-throughput MS/MS were used to
      examine induced changes in protein abundance and protein modification.
      Significant changes were observed as early as 2 h following the onset of insect
      feeding. Among the insect-induced proteins are a series of related small heat
      shock proteins, other stress response proteins, proteins involved in secondary
      metabolism, oxidoreductases, and a novel spruce protein. Comparison of protein
      expression and cDNA microarray profiles of induced spruce stem tissues reveals
      the complementary nature of transcriptome and proteome analyses and the need to
      apply a multifaceted approach to the large-scale analysis of plant defense
      systems.

PMID- 17205608
TI  - Differential expression of sarcoplasmic proteins in four heterogeneous ovine
      skeletal muscles.
AB  - Fiber-type distribution is known to vary widely within and between muscles
      according to differences in muscle functions. 2-DE and MALDI-MS were used to
      investigate the molecular basis of muscle fiber type-related variability. We
      compared four lamb skeletal muscles with heterogeneous fiber-type composition
      that are relatively rich in fast-twitch fiber types, i.e., the semimembranosus,
      vastus medialis, longissimus dorsi, and tensor fasciae latae (TL). Our results
      clearly showed that none of the glycolytic metabolism enzymes detected, including
      TL which was most strongly glycolytic, made intermuscular differentiation
      possible. Muscle differentiation was based on the differential expression of
      proteins involved in oxidative metabolism, including not only citric acid cycle
      enzymes but also other classes of proteins with functions related to oxidative
      metabolism, oxidative stress, and probably to higher protein turnover. Detected
      proteins were involved in transport (carbonate dehydratase, myoglobin, fatty acid
      binding protein), repair of misfolding damage (heat shock protein (HSP) 60 kDa,
      HSP-27 kDa, alpha-crystallin beta subunit, DJ1, stress-induced phosphoprotein),
      detoxification or degradation of impaired proteins (GST-Pi, aldehyde
      dehydrogenase, peroxiredoxin, ubiquitin), and protein synthesis (tRNA
      synthetase). The fractionating method led to the detection of proteins involved
      in different functions related to oxidative metabolism that have not previously
      been shown concomitancy.

PMID- 17205609
TI  - Identification of bactenecin-1 in cervicovaginal fluid by two-dimensional
      electrophoresis in an ovine model of preterm labour.
AB  - Preterm labour is a major problem in obstetrics. Timely intervention with
      available treatments is hampered by the lack of a reliable test of imminent
      preterm delivery. Current methods of diagnosis are based on the detection of
      breakdown products of foetal membranes or structural changes to the cervix when
      preterm labour is well established. The aim of this study was to screen the
      cervicovaginal fluid (CVF) proteome to identify labour-associated proteins that
      could be used as markers of imminent preterm delivery. Labour was induced in
      sheep at 135 days of gestation (term 147 days) by foetal infusion of
      dexamethasone (1 mg/24 h). CVF samples were collected before and 28 h after the
      start of infusion as well as at delivery (58.7 +/- 1.9 after the start of
      infusion, n = 5). One protein that was upregulated eight-fold, was bactenecin-1,
      a member of the cathelicidin family of antimicrobial proteins. This antimicrobial
      protein warrants further investigation as a marker of preterm labour,
      particularly during the period after the initiation of labour but before there is
      marked cervical connective tissue breakdown.

PMID- 17205610
TI  - Towards a consensus on datasets and evaluation metrics for developing B-cell
      epitope prediction tools.
AB  - A B-cell epitope is the three-dimensional structure within an antigen that can be
      bound to the variable region of an antibody. The prediction of B-cell epitopes is
      highly desirable for various immunological applications, but has presented a set
      of unique challenges to the bioinformatics and immunology communities. Improving
      the accuracy of B-cell epitope prediction methods depends on a community
      consensus on the data and metrics utilized to develop and evaluate such tools. A
      workshop, sponsored by the National Institute of Allergy and Infectious Disease
      (NIAID), was recently held in Washington, DC to discuss the current state of the
      B-cell epitope prediction field. Many of the currently available tools were
      surveyed and a set of recommendations was devised to facilitate improvements in
      the currently existing tools and to expedite future tool development. An
      underlying theme of the recommendations put forth by the panel is increased
      collaboration among research groups. By developing common datasets, standardized
      data formats, and the means with which to consolidate information, we hope to
      greatly enhance the development of B-cell epitope prediction tools.

PMID- 17205611
TI  - Immunotherapy with a ragweed vaccine.

PMID- 17205612
TI  - Transmission of human herpesvirus 8 by blood transfusion.

PMID- 17205613
TI  - Medical education after the Flexner report.

PMID- 17205614
TI  - Medical education after the Flexner report.

PMID- 17205615
TI  - Medical education after the Flexner report.

PMID- 17205616
TI  - The tuberous sclerosis complex.

PMID- 17205617
TI  - The tuberous sclerosis complex.

PMID- 17205618
TI  - Endocannabinoid-dependent regulation of feedforward inhibition in cerebellar
      Purkinje cells.

PMID- 17205619
TI  - Nursepreneurship': the best of both worlds?

PMID- 17205620
TI  - Simulation of ozone depletion using ambient irradiance supplemented with UV
      lamps.
AB  - In studies of the biological effects of UV radiation, ozone depletion can be
      mimicked by performing the study under ambient conditions and adding radiation
      with UV-B lamps. We evaluated this methodology at three different locations along
      a latitudinal gradient: Rimouski (Canada), Ubatuba (Brazil) and Ushuaia
      (Argentina). Experiments of the effect of potential ozone depletion on marine
      ecosystems were carried out in large outdoor enclosures (mesocosms). In all
      locations we simulated irradiances corresponding to 60% ozone depletion, which
      may produce a 130-1900% increase in 305 nm irradiance at noon, depending on site
      and season. Supplementation with a fixed percentage of ambient irradiance
      provides a better simulation of irradiance increase due to ozone depletion than
      supplementation with a fixed irradiance value, particularly near sunrise and
      sunset or under cloudy skies. Calculations performed for Ushuaia showed that, on
      very cloudy days, supplementation by the square-wave method may produce
      unrealistic irradiances. Differences between the spectra of the calculated
      supplementing irradiance and the lamp for a given site and date will be a
      function of the time of day and may become more or less pronounced according to
      the biological weighting function of the effect under study.

PMID- 17205621
TI  - Ultraviolet-B radiation effects on the structure and function of lower trophic
      levels of the marine planktonic food web.
AB  - The impact of UV-B radiation (UVBR; 280-320 nm) on lower levels of a natural
      plankton assemblage (bacteria, phytoplankton and microzooplankton) from the St.
      Lawrence Estuary was studied during 9 days using several immersed outdoor
      mesocosms. Two exposure treatments were used in triplicate mesocosms: natural
      UVBR (N treatment, considered as the control treatment) and lamp-enhanced UVBR (H
      treatment, simulating 60% depletion of the ozone layer). A phytoplankton bloom
      developed after day 3, but no significant differences were found between
      treatments during the entire experiment for phytoplankton biomass (chlorophyll a
      and cell carbon) nor for phytoplankton cell abundances from flow cytometry and
      optical microscopy of three phytoplankton size classes (picoplankton,
      nanoplankton and microplankton). In contrast, bacterial abundances showed
      significantly higher values in the H treatment, attributed to a decrease in
      predation pressure due to a dramatic reduction in ciliate biomass (approximately
      70-80%) in the H treatment relative to the N treatment. The most abundant ciliate
      species were Strombidinium sp., Prorodon ovum and Tintinnopsis sp.; all showed
      significantly lower abundances under the H treatment. P. ovum was the less
      affected species (50% reduction in the H treatment compared with that of the N
      control), contrasting with approximately 90% for the other ones. Total specific
      phytoplanktonic and bacterial production were not affected by enhanced UVBR.
      However, both the ratio of primary to bacterial biomass and production decreased
      markedly under the H treatment. In contrast, the ratio of phytoplankton to
      bacterial plus ciliate carbon biomass showed an opposite trend than the previous
      results, with higher values in the H treatment at the end of the experiment.
      These results are explained by the changes in the ciliate biomass and suggest
      that UVBR can alter the structure of the lower levels of the planktonic community
      by selectively affecting key species. On the other hand, linearity between
      particulate organic carbon (POC) and estimated planktonic carbon was lost during
      the postbloom period in both treatments. On the basis of previous studies, our
      results can be attributed to the aggregation of carbon released by cells to the
      water column in the form of transparent exopolymer particles (TEPs) under
      nutrient limiting conditions. Unexpectedly, POC during such a period was higher
      in the H treatment than in controls. We hypothesize a decrease in the ingestion
      of TEPs by ciliates, in coincidence with increased DOC release by phytoplankton
      cells under enhanced UVBR. The consequences of such results for the carbon cycle
      in the ocean are discussed.

PMID- 17205622
TI  - Vertical mixing and ecological effects of ultraviolet radiation in planktonic
      communities.
AB  - We present a mathematical model for a phytoplankton-zooplankton system, based on
      a predator-prey scheme. The model considers the effects of sinking in the
      phytoplankton, vertical mixing and attenuation of photosynthetically active
      radiation (PAR) and ultraviolet radiation (UVR) in the water column. In a first
      approach, the model was studied under conditions of average PAR irradiance and
      shows fluctuations and stable equilibrium points. Secondly, we introduced the
      effects of photoperiod and photoinhibition by UVR and vertical mixing. Under
      these conditions, the phytoplankton biomass oscillates depending on the combined
      effects of UVR and mixing. Higher inhibition by UVR and longer mixing periods can
      induce strong fluctuations in the system but can also produce higher plankton
      peaks.

PMID- 17205623
TI  - The whole is more than the sum of its parts: Modeling community-level effects of
      UVR in marine ecosystems.
AB  - The effect of UVB radiation (UVBR, 290-320 nm) on the dynamics of the lower
      levels of the marine plankton community was modeled. The model was built using
      differential equations and shows a good fit to experimental data collected in
      mesocosms (defined as large enclosures of 1500 L filled with natural marine
      waters). Some unexpected results appear to be possible by indirect effects in
      prey (bacteria, phytoplankton and heterotrophic flagellates). In particular,
      apparent competition appears between small phytoplankton and bacteria. This
      effect is caused by a shared predator (ciliates). Another remarkable effect is an
      increase in bacteria and flagellates populations due to enhanced UVBR. This
      effect is similar to that observed under mesocosm experimental conditions and is
      related to the decrease of predation due to the direct damage to predators
      (ciliates) by UVBR. The effect of UVBR changing interaction coefficients may be
      dramatic on the community structure, producing big changes in equilibrium
      populations, as demonstrated by sensitivity analysis of the model. In order to
      generalize these results to field conditions it will be necessary to increase
      model complexity and include extra organic mater sources, mixing and sinking
      effects and predation by large zooplankton. This work shows that UVBR may produce
      community global responses that are consequence of both direct and indirect
      effects among populations.

PMID- 17205624
TI  - Effects of enhanced UV-B on pigment-based phytoplankton biomass and composition
      of mesocosm-enclosed natural marine communities from three latitudes.
AB  - A series of three outdoor mesocosm experiments was undertaken in Rimouski
      (Canada), Ubatuba (Brazil) and Ushuaia (southern Argentina) to examine the
      effects of lamp-enhanced UV-B (280-320 nm) on phytoplankton communities isolated
      from seawater at each site. Detailed pigment composition was used to identify
      these communities. Each experiment compared three replicated UV-B treatments,
      consisting of natural sunlight conditions (NUVB), low-level UV-B enhancement
      corresponding to local 30% ozone depletion (LUVB) and high-level enhancement
      corresponding to 60% ozone depletion (HUVB). Each mesocosm (ca 2 m deep) was
      mixed continuously (turnover time, ca 1.3 h) and samples were obtained daily over
      7-10 days. In Rimouski a large diatom bloom occurred during the first week.
      Repeated-measures analysis of variance (RM-ANOVA), with time as the repeated
      factor, showed slight but statistically significant increases in the chlorophyll
      (Chl) a level with the HUVB treatment, which were especially obvious over the
      last 3 days of the experiment. A large decrease in grazers (ciliates) that was
      observed concurrently with this treatment is the most likely explanation for the
      increase in Chl a level. The lack of negative effect on algal biomass by enhanced
      UV-B is attributed to the mixing inside the mesocosms and to the relatively low
      UV-B penetration. In Ubatuba levels of most pigments decreased over time,
      particularly fucoxanthin, Chl c3 and alloxanthin. The RM-ANOVA showed no effect
      of the UV-B treatments, except for Chl c3, which had significantly lower
      concentrations under natural UVB conditions, indicating that enhanced UV-B
      directly or indirectly favored Chl c3 algae (likely prymnesiophytes). Although
      particulate organic carbon concentration was significantly larger during HUVB
      treatment than during the other treatments, Chl a was unaffected, suggesting that
      enhanced UV-B favored heterotrophs. Lack of algal growth during this experiment
      was attributed to low nutrient concentrations (which were the lowest of the three
      sites), high irradiances (which were the highest noon incident photosynthetically
      available radiation and UV of the three sites) and UV-B penetration down to the
      bottom of the mesocosms. In Ushuaia a small bloom took place over the first 5
      days. The RM-ANOVA showed no overall effect of the UV-B treatments for any of the
      pigments examined but on the last 3 days of the experiment several green algae
      type pigments, such as Chl b and siphonein, showed increased concentrations under
      the HUVB treatment. UV-B enhancement hence favored green algae, as seen from the
      stronger increase over time in the ratio of Chl b to Chl a associated with the
      HUVB treatment. UV-B enhancement also seemed to cause a slight decrease in
      physiological condition, because the relative concentration of chlorophyllide a
      and some pheophorbides that may be the product of dying algae increased during
      the HUVB treatments in Ubatuba and particularly in Ushuaia (where UV-B also
      penetrated to the bottom of mesocosms). For all three sites changes in
      phytoplankton biomass due to the UV-B treatments were minor, even though UV-B
      enhancement was important. This study indicates that effects of enhanced UV-B on
      the community structure of both phytoplankton and their grazers are potentially
      more important than effects on overall algal biomass.

PMID- 17205625
TI  - Occurrence of photoprotective compounds in yeasts from freshwater ecosystems of
      northwestern Patagonia (Argentina).
AB  - In this paper we present the results of research on the occurrence, induction and
      role of photoprotective compounds (PPCs) present in native aquatic yeasts from
      freshwater Patagonian ecosystems. We focus on the effect of UV radiation (UVR) as
      a factor that controls the level of photoprotection of yeasts, and explore its
      potential significance in shaping yeast distributional patterns. The research
      presented here combines field surveys and laboratory work, including the
      isolation and culture of native yeasts strains, and laboratory assays under
      different radiation conditions. The results obtained suggest that yeasts are
      common dwellers of oligotrophic Patagonian water bodies, and provide the first
      evidence of the distribution of PPC (carotenoid and mycosporine)-producing yeasts
      in temperate freshwaters. A greater proportion of carotenogenic yeasts were
      observed in high-elevation lakes. The yeast strains isolated from these
      environments were found to produce higher amounts of mycosporines (MYCs), and to
      present higher tolerance to UVB exposure than those from piedmont lakes.
      Patagonian yeasts have only one type of MYC, mycosporine-glutaminol-glucoside
      (myc-glu-glu), which seems common to all other yeasts. By analyzing the
      production of myc-glu-glu in a large number of yeasts belonging to different
      taxonomic groups, we propose that this compound may have potential use as a
      chemotaxonomic marker in yeast systematics. Collectively, our work reveals that
      in Patagonian freshwater yeasts there is an apparent relationship between the
      ability to produce PPCs, their tolerance to UV exposure and their success in
      colonizing habitats highly exposed to UVR.

PMID- 17205626
TI  - Effects of photodegradation on the physical and antioxidant properties of
      melanosomes isolated from retinal pigment epithelium.
AB  - Melanosomes of the retinal pigment epithelium (RPE) are relatively long-lived
      organelles that are theoretically susceptible to changes induced by exposure to
      visible light. Here melanosomes were isolated from porcine RPE cells and
      subjected to high intensity visible light to determine the effects of
      illumination on melanosome structure and on the content and antioxidant
      properties of melanin. As compared to untreated melanosomes, illuminated granules
      showed morphologic changes consistent with photodegradation, which included
      variable reductions in electron density demonstrated by transmission electron
      microscopy (TEM), and particle fragmentation and surface disruption revealed by
      scanning electron microscopy (SEM) and atomic force microscopy. Illuminated
      melanosomes had lower melanin content, indicated by measures of absorbance and
      electron spin resonance (ESR) signal intensity, and reduced ability to bind iron,
      shown by chemical and ESR analyses. Compared to untreated melanosomes, ESR-spin
      trapping analyses further indicated that illuminated melanosomes show increased
      photogeneration of superoxide anion and reduced ability to inhibit the iron ion
      catalyzed free radical decomposition of hydrogen peroxide. It appears therefore
      that visible light irradiation can disrupt the structure of RPE melanosomes and
      reduce the amount and antioxidant properties of melanin. Some of these changes
      occur in human RPE melanosomes with aging and the results obtained here suggest
      that visible light irradiation is at least partly responsible. The consequence of
      light-induced changes in RPE melanosomes may be a diminished capacity of melanin
      to help protect aged cells from oxidative damage, perhaps increasing the risk of
      diseases with an oxidative stress component such as age-related macular
      degeneration.

PMID- 17205627
TI  - Microspectroscopy of the photosynthetic compartment of algae.
AB  - We performed microspectroscopic evaluation of the pigment composition of the
      photosynthetic compartments of algae belonging to different taxonomic divisions
      and higher plants. The feasibility of microspectroscopy for discriminating among
      species and/or phylogenetic groups was tested on laboratory cultures. Gaussian
      bands decompositions and a fitting algorithm, together with fourth-derivative
      transformation of absorbance spectra, provided a reliable discrimination among
      chlorophylls a, b and c, phycobiliproteins and carotenoids. Comparative analysis
      of absorption spectra highlighted the evolutionary grouping of the algae into
      three main lineages in accordance with the most recent endosymbiotic theories.

PMID- 17205628
TI  - UV Index on tilted surfaces.
AB  - Solar ultraviolet erythemal irradiance (UVER) has been studied on inclined planes
      with different orientations in Valencia, Spain. To do this a platform was
      designed that could turn through 90 degrees on its own axis. The radiometers were
      inclined at an angle close to the latitude of Valencia (39.5 degrees N). Using
      two timers the platform could be turned through 90 degrees every 5 min. On clear
      or partially cloudy days, including those with different turbidity values, it was
      observed that the UVER showed a maximum at 1200 h GMT, very close to solar noon,
      in the north and south positions, while the maximum for east and west
      orientations was found at approximately one hour before and one hour after midday
      respectively. It was also observed how the irradiance for the south orientation
      was greater and for the north was less than for the horizontal plane, as well as
      the opposite performances of the east and west orientations, for four days close
      to the summer and winter solstices and each equinox. Some experimental results
      were also compared with the results from the SMARTS2.9 model for the same
      conditions. It was found that the model frequently overestimated the experimental
      data. With respect to the maximum calculated UV Index in the different planes
      this was always higher for the south orientation than for the north, while it was
      similar for east and west orientations throughout the year. Finally the
      accumulated erythemal dosage for the considered period was obtained as a function
      of phototype and orientation, confirming that the accumulated erythemal dosage
      decreased by around 37% in the north orientation compared to the horizontal
      value, while in the south position it was only 6% less and some 20% and 15% less
      in the east and west positions, respectively.

PMID- 17205629
TI  - The fluence rate determines the synergistic interaction of UV radiation and heat
      for mitotic recombination and cell inactivation in yeasts.
AB  - The significance of the UV fluence rate for the synergistic interaction of UV
      light (254 nm) and heat was demonstrated for the frequency of mitotic
      recombination in a wild-type diploid yeast of Saccharomyces cerevisiae (strain
      T1) and for cell inactivation of two wild-type diploid yeast of S. cerevisiae
      (strains T1, XS800). It was shown for mitotic recombination that a decrease in
      the intensity of UV exposure results in the necessity of decreasing the
      temperature at which UV irradiation occurs to provide the same value of the
      synergistic enhancement ratio. For cell inactivation, there was a specific
      temperature maximizing the synergistic effect for any constant fluence rate and
      the temperature range, synergistically increasing the inactivation effect of UV
      radiation, should be shifted to lower temperatures with a decrease in the fluence
      rate. To interpret the results observed, a simple mathematical model of the
      synergistic interaction was applied. The model suggests that the synergistic
      interaction of UV light and hyperthermia is expected to result from some
      additional effective damages arising from the interaction of some sublesions
      induced by both agents. On the basis of data obtained, it was supposed that the
      synergistic interaction of these factors might take place at small intensities of
      UV light and temperatures existing in the biosphere. In other words, for a long
      duration of interaction, which is important for problems of UV light protection
      and health effects, one can expect a synergistic interaction of this factor with
      environmental heat or physiological temperatures and thereby an increase in their
      inactivating and genetic consequences.

PMID- 17205630
TI  - Enhancement of fluoresceinyl cypridina luciferin analog chemiluminescence by
      human serum albumin for singlet oxygen detection.
AB  - Fluoresceinyl cypridina luciferin analog (FCLA) is a chemiluminescence (CL) probe
      for detecting reactive oxygen species (ROS). Its efficiency for detecting singlet
      oxygen (1O2) can be significantly enhanced in the presence of human serum albumin
      (HSA). This phenomenon may apply to important applications for both research and
      clinical testing, because of the broad presence of HSA in the human system. In
      the current study the mechanism of the FCLA-HSA CL system is studied by means of
      direct CL measurement and spectroscopy techniques. Our results show that FCLA can
      combine with HSA via a single binding site to form a complex. The CL efficiency
      of the system is largely governed by an intersystem energy transfer between the
      two components upon interaction with 1O2. The CL production reaches maximum in a
      synergetic manner when equal amounts of FCLA and HSA are present simultaneously,
      but production is less at other ratios. The results also show that the
      combination of FCLA with HSA does not significantly alter the ROS selectivity of
      FCLA. In conclusion, our study shows that FCLA and HSA can combine and form a
      complex with higher CL efficiency. This provides us a new approach in designing
      CL techniques for studying ROS.

PMID- 17205631
TI  - On the role of iron and one of its chelating agents in the production of
      protoporphyrin IX generated by 5-aminolevulinic acid and its hexyl ester
      derivative tested on an epidermal equivalent of human skin.
AB  - Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) or its derivatives as
      precursors of protoporphyrin IX (PPIX) is routinely used in dermatology for the
      treatment of various pathologies. However, this methodology suffers to some
      extent from a limited efficacy. Therefore, the main goal of this study was to
      investigate the modulation and pharmacokinetics of PPIX buildup after a 5 h
      incubation with ALA (1.5 mM) and one of its derivatives, the hexyl ester of ALA
      (h-ALA) (1.5 mM), on the human epidermal equivalent Epidex. PPIX production was
      modulated with (L+) ascorbic acid iron (II) salt (LAI) or the iron (II)-specific
      chelating agent deferoxamine (DFO). PPIX fluorescence from the Epidex layers was
      measured up to 150 h after the precursor administration using a
      microspectrofluorometer (lambda(ex): 400 +/- 20 nm; lambda(det): 635 nm). The
      maximum PPIX fluorescence intensity induced by h-ALA was about 1.7 x larger than
      that induced by ALA. The addition of DFO resulted in a more than 50% increase in
      PPIX fluorescence for both precursors. The decay half life measured for PPIX
      fluorescence is 30 and 42.5 h, respectively, for ALA and h-ALA. These half lives
      are doubled when the samples contain DFO. In the samples with the highest
      fluorescence intensity, a modified fluorescence spectrum was observed after 10 h,
      with the emergence of a peak at 590 nm, which is attributed to zinc
      protoporphyrin IX (Zn PPIX).

PMID- 17205632
TI  - Unusual high exposure to ultraviolet-C radiation.
AB  - UV radiation is known to cause acute and chronic eye and skin damage. The present
      case report describes a 90 min accidental exposure to UV-C radiation of 26
      medical school students. Germicidal lamps were lit due to a malfunctioning of the
      timer system. Several hours after irradiation exposure, all subjects reported the
      onset of ocular symptoms, subsequently diagnosed as photokeratitis, and skin
      damage to the face, scalp and neck. While the ocular symptoms lasted 2-4 days,
      the sunburn-like condition produced significant erythema followed by deep skin
      exfoliation. The irradiation was calculated to be approximately 700 mJ cm(-2)
      absorbed energy, whereas the actual radiation emitted by the lamps was 0.14 mW
      cm(-2) (the radiometric measurements confirmed these calculi, because the
      effective irradiance measured from the height of the autopsy table to about 1 m
      under the UV-C lamp varied from 0.05 to 0.25 mW cm(-2)) but, more likely, the
      effective irradiance, according to skin phototype and symptoms, was between 50
      and 100 mJ cm(-2). The ocular and skin effects produced by such a high
      irradiation (largely higher than that accepted by the American Conference of
      Governmental Industrial Hygienists [ACGIH] threshold limit values [TLVs])
      appeared reversible in a relatively short time.

PMID- 17205633
TI  - UVB dose-toxicity thresholds and steady-state DNA-photoproduct levels during
      chronic irradiation of inbred Xenopus laevis tadpoles.
AB  - Environmental stressors that severely impact some species more than others can
      alter ecosystems and threaten biodiversity. Genotoxic stress, such as solar UV-B
      irradiance, may induce levels of DNA damage at rates that exceed repair
      capacities in some species but remain below repair capacities in other species.
      Repair rates would seem to establish toxicity thresholds. We used inbred Xenopus
      laevis tadpoles in the laboratory to test the hypothesis that balances between
      rates of induction of cyclobutane pyrimidine dimers (CPDs; the major UV-B
      photoproduct in DNA) and rates of CPD removal (repair) can determine UV-B
      toxicity thresholds. As rates of chronic UV-B irradiance were progressively
      increased by decreased shielding of lamps, survival decreased sharply over a
      relatively narrow range of dose rates. Apparent toxicity thresholds were
      associated with large increases in steady-state CPD levels. Induction at twice
      the measured removal (repair) rate produced sustained high CPDs and 100%
      mortality. Induction at one-half the removal rate resulted in negligible CPD
      levels and low mortality. Increased intensity of visible radiation available to
      drive CPD photoreactivation, mimicking interspecies variation in DNA repair
      capacity, reduced steady-state CPD levels and increased survival at UV-B dose
      rates that were previously toxic, resulting in increased thresholds of apparent
      toxicity. We suggest that threshold effects due to DNA repair should generally be
      considered in assessments of effects of genotoxic agents on species-specific
      population decreases and human health risks.

PMID- 17205634
TI  - Two native pools of phytochrome A in monocots: Evidence from fluorescence
      investigations of phytochrome mutants of rice.
AB  - Fluorescence investigations of phytochrome (phy) in rice (Oryza sativa L. cv.
      Nipponbare) mutants deficient in phyA, phyB and phyA plus phyB were performed.
      Total content of the pigment (P(tot)) and its spectroscopic and photochemical
      characteristics were determined in different parts of the dark-grown and far-red
      light (FR)-grown coleoptiles. Spectroscopically, phyA in the phyB mutant was
      identical to phyA in the wild-type (WT) and the extent of the conversion from Pr
      to lumi-R at 85 K was the same for phyA in both lines and varied similarly,
      depending on the part of the coleoptile used. The latter finding proved that phyA
      in rice is heterogeneous and comprises two phyA populations, phyA' and phyA".
      Functional properties of phyA were also determined. In the dark the phyB mutant
      had a higher content of phyA, inactive protochlorophyllide (Pchlide633) and
      active protochlorophyllide (Pchlide655) than WT and its coleoptile was longer,
      indicating that phyB may affect the development of WT seedlings in the dark.
      Constant FR drastically reduced the content of phyA, Pchlide633 and Pchlide655
      and brought about coleoptile shortening and appearance of the first leaf, whereas
      pulsed FR of equal fluence was less effective. This suggested that the reactions
      were primarily of the high irradiance responses type, which are likely to be
      mediated by phyA'. The effects on protochlorophyllide biosynthesis and growth
      responses type were more pronounced in the phyB mutant than in the WT seedlings,
      which can be connected with the higher phyA' content in the phyB mutant and/or
      phyB interference with its action in WT seedlings. In the phyA mutant induction
      of Pchlide633 and Pchlide655 biosynthesis was observed under constant FR,
      indicating that phyC may be responsible for this effect.

PMID- 17205635
TI  - Relevance of sunscreen application method, visible light and sunlight intensity
      to free-radical protection: A study of ex vivo human skin.
AB  - With the continued rise in skin cancers worldwide there is a need for effective
      skin protection against sunlight damage. It was shown previously that sunscreens,
      which claimed UVA protection (SPF 20+), provided limited protection against UV
      induced ascorbate radicals in human skin. Here the results of an electron spin
      resonance (ESR) investigation to irradiate ex vivo human skin with solar
      simulated light are reported. The ascorbate radical signal in the majority of
      skin samples was directly proportional to the irradiance over relevant sunlight
      intensities (0.9-2.9 mW cm(-2)). Radical production (substratum-corneum) by UV
      (wavelengths < 400 nm) and visible components (> 400 nm) was approximately 67%
      and 33% respectively. Ascorbate radicals were in steady state concentration at
      low irradiance (approximately 1 mW cm(-2) equivalent to UK sunlight), but at
      higher irradiance (approximately 3 mW cm(-2)) decreased with time, suggesting
      ascorbate depletion. Radical protection by a four star-rated sunscreen (with UVA
      protection) was optimal when applied as a thin film (40-60% at 2 mg cm(-2)) but
      less so when rubbed into the skin (37% at 4 mg cm(-2) and no significant
      protection at 2 mg cm(-2)), possibly due to cream filling crevices, which reduced
      film thickness. This study validates ESR determinations of the ascorbate radical
      for quantitative protection measurements. Visible light contribution to radical
      production, and loss of protection when sunscreen is rubbed into skin, has
      implications for sunscreen design and use for the prevention of free-radical
      damage.

PMID- 17205636
TI  - Is alcohol always harmful?

PMID- 17205637
TI  - Medical education primarily a subject of the humanities.

PMID- 17205638
TI  - [Echo-guided compression sclerotherapy using foam: an improvement in the
      treatment of varicose veins].

PMID- 17205639
TI  - The expert consensus guideline series. Pharmacotherapy of depressive disorders in
      older patients.
AB  - OBJECTIVES: Depression in older patients contributes to personal suffering and
      family disruption and increases disability, medical morbidity, mortality, suicide
      risk, and healthcare utilization. The majority of clinical trials of
      antidepressant treatments are conducted in younger patients. For this reason,
      clinicians often have to extrapolate from studies in populations that do not
      present the same problems as older patients. For example, older patients often
      have serious coexisting medical conditions that may contribute to the depression
      and complicate the choice of treatment. Older patients as a rule need to be on
      many medications, some of which may contribute to depression and/or interact with
      antidepressants. Finally, older adults metabolize medications slowly and are more
      sensitive to side effects than younger patients. Because of these complexities,
      we conducted a consensus survey of expert opinion on the pharmacotherapy of
      depressive disorders in older patients to address clinical questions not
      definitively answered in the research literature. METHOD: After reviewing the
      literature and convening a work group of experts, we prepared a written survey
      with 64 questions that asked about 857 options. 618 of the options were scored
      using a modified version of the RAND 9-point scale for rating appropriateness of
      medical decisions. For the other options, the experts were asked to write in
      answers (e.g., average doses) or to check a box to indicate their preferred
      answer. We sent the survey to 50 national experts on geriatric depression, all of
      whom completed it. Consensus on each option was defined as a nonrandom
      distribution of scores by chi-square "goodness-of-fit" test. We assigned a
      categorical rank (first line/preferred choice, second line/alternate choice,
      third line/usually inappropriate) to each option based on the 95% confidence
      interval around the mean rating. Guideline tables indicating preferred treatment
      strategies were then developed for key clinical situations. RESULTS: The expert
      panel reached consensus on 89% of the options rated on the 9-point scale. The
      experts stress the importance of identifying coexisting medical conditions that
      may be contributing to the depression or complicate treatment. For unipolar
      nonpsychotic major depression, the preferred strategy is an antidepressant
      (selective serotonin reuptake inhibitor [SSRI] or venlafaxine XR preferred) plus
      psychotherapy. For unipolar psychotic major depression, the treatment of choice
      is an antidepressant (SSRI or venlafaxine XR) plus one of the newer atypical
      antipsychotics. Electroconvulsive therapy is also first line. For dysthymic
      disorder or persistent milder depression, the experts recommend combining an
      antidepressant (SSRIs preferred) and psychotherapy. If the patient has a comorbid
      medical condition (e.g., hypothyroidism) that is contributing to the depression,
      the experts recommend treating both the depression and the medical condition from
      the outset. The SSRIs were the top-rated antidepressants for all types of
      depression. Among them, the experts gave the highest ratings for efficacy and
      tolerability to citalopram and sertraline. Paroxetine was another first-line
      option, and fluoxetine was rated high second line. The preferred psychotherapy
      techniques for treating depression in older patients are cognitive-behavioral
      therapy, supportive psychotherapy, problem-solving psychotherapy, and
      interpersonal psychotherapy. The experts also give strong support to including
      appropriate psychosocial interventions (e.g., psychoeducation, family counseling,
      visiting nurse services) in the treatment program. The majority of experts would
      continue treatment with antidepressant medication for at least 1 year if a
      patient has had a single episode of severe unipolar major depression, for 1-3
      years for a patient who has had 2 such episodes, and for longer than 3 years if
      there is a history of 3 or more episodes. CONCLUSIONS: The experts reached a high
      level of consensus on the appropriateness of including both antidepressant
      medication, specifically SSRIs, and nonpharmacological modalities in treatment
      plans for severe depression. Within the limits of expert opinion and with the
      expectation that future research data will take precedence, these guidelines
      provide direction for addressing common clinical dilemmas in older individuals.
      They can be used to inform clinicians and educate patients regarding the relative
      merits of a variety of interventions. Nonetheless, the guidelines cannot address
      the complexities involved in the care of each individual patient and can be most
      helpful in the hands of experienced clinicians.

PMID- 17205640
TI  - [Gemfibrozil induced rhabdomyolysis in a patient with undiscovered
      hypothyroidism].

PMID- 17205641
TI  - [Mycoplasma pneumoniae pneumonia and acute respiratory distress syndrome].

PMID- 17205642
TI  - [Spontaneous pneumomediastinum associated to Speed inhalation].

PMID- 17205643
TI  - [Epiploic appendagitis: An unusual case of acute abdominal pain].

PMID- 17205644
TI  - [The prevalence of anemia in patients with chronic heart failure].

PMID- 17205645
TI  - Anti-HIV agents. Integrase inhibitors come of age.

PMID- 17205646
TI  - Anti-HIV agents. Merck's integrase inhibitor--short-term efficacy.

PMID- 17205647
TI  - Anti-HIV agents. Some drug interactions with Merck's integrase inhibitor.

PMID- 17205648
TI  - Co-infections.  Can hepatitis C virus help keep cholesterol levels low?

PMID- 17205649
TI  - Bibliography. Current world literature. Cancer biology.

PMID- 17205650
TI  - Anti-HIV agents. Selected highlights from the XVI International AIDS Conference.
      Toronto, Canada, 13-18 August 2006.

PMID- 17205651
TI  - Anti-HIV agents. Darunavir shows its strength.

PMID- 17205652
TI  - Anti-HIV agents. Merck integrase inhibitor.

PMID- 17205653
TI  - Anti-HIV agents. Access denied--keeping HIV out with entry inhibitors.

PMID- 17205654
TI  - Anti-HIV agents. Maraviroc in treatment-experienced PHAs.

PMID- 17205655
TI  - Mental health. Vancouver team uncovers self-medication with crystal meth.

PMID- 17205656
TI  - [Filamentous bacterial infection developing after tuberculous sequela and causing
      massive hemoptysis].

PMID- 17205657
TI  - [Autopsy study of chronic necrotic aspergillosis of the lung associated with
      organizing pneumonia].

PMID- 17205658
TI  - [Significance and keypoints in fungal allergens in airway allergy].

PMID- 17205659
TI  - [Postprandial glycemia in diabetes patients: assessing this indicator].

PMID- 17205660
TI  - [Prophylactic administration of fluconazole and itraconazole in febrile
      neutropenia associated with hematopoietic malignancy].

PMID- 17205661
TI  - [A case of IgG kappa-type multiple myeloma complicated with carinii pneumonia
      following thalidomide administration].

PMID- 17205662
TI  - [Analysis of serum Aspergillus galactomannan contents conducted at our hospital
      during the past 2 years].

PMID- 17205663
TI  - Overview of the immunization product quality control practices of vaccinators in
      Monteregie.

PMID- 17205664
TI  - Population-based epidemiology of rotavirus hospitalisations in Switzerland.
AB  - BACKGROUND: Rotaviruses (RV) are the most common cause of dehydrating
      gastroenteritis requiring hospitalisation in children <5 years of age. A new
      generation of safe and effective RV vaccines is available. Accurate data
      describing the current burden of RV disease in the community are needed to devise
      appropriate strategies for vaccine usage. METHODS: Retrospective, population
      based analysis of RV hospitalisations in children <5 years of age during a 5-year
      period (1999-2003) in a both urban and rural area inhabited by 12% of the Swiss
      population. RESULTS: Of 406 evaluable cases, 328 were community-acquired RV
      infections in children <5 years of age. RV accounted for 38% of all
      hospitalisations for gastroenteritis. The overall hospitalisation incidence in
      the <5-year-old was 1.5/1000 child-years (peak incidence, 2.6/1000 child-years in
      children aged 13-24 months). The incidence of community-acquired RV
      hospitalisations was significantly greater in children of non-Swiss origin (3.0
      vs. 1.1/1000 child-years, relative risk 2.7; 95% CI 2.2-3.4), who were younger,
      but tended to be less severely dehydrated on admission than Swiss children. In
      comparison with children from urban areas, RV hospitalisation incidence was
      significantly lower among those residing in the remote mountain area (0.71 vs.
      1.71/1000 child years, relative risk 2.2, 95% CI 1.6-3.1). CONCLUSION: Population
      based RV hospitalisation incidence was low in comparison with other European
      countries. Significantly greater hospitalisation rates among children living in
      urban areas and those from non-Swiss families indicate that factors other than
      the severity of RV-induced dehydration are important driving forces of hospital
      admission.

PMID- 17205665
TI  - Takotsubo and Kounis syndrome: is there any association?

PMID- 17205666
TI  - The introduction of a performance-based system for funding research.

PMID- 17205667
TI  - Impact factors and the law of unintended consequences.

PMID- 17205668
TI  - How to survive (and enjoy) doing a thesis: the experiences of a methodological
      working group.
AB  - 'Doing a thesis', whether for Masters or PhD, can be a lonely and tortuous
      journey. This article offers a complementary process to the traditional
      apprenticeship supervision model. It describes the experiences of students who
      during their thesis research met monthly in a grounded theory working group. They
      reflected on their experiences during a focus group interview. After describing
      the background to how the group started in 1999 and exploring some of the ideas
      in the literature concerning the thesis experience, the article presents the
      interview. To focus the presentation, specific questions are used as category
      headings. Overall, the participants found attending the group was a "life-line"
      that gave them "hope" and was complementary to the supervision process. Through
      the support of peers, guidance from those ahead in the process, and consultancy
      with teachers and visiting methodological scholars, these students not only
      successfully completed their theses, but reported that they had some enjoyment
      along the way. This is the fifteenth in a series of articles which have been
      based on interviews with nursing and midwifery researchers, and were primarily
      designed to offer the beginning researcher a first-hand account of the experience
      of using particular methodologies.

PMID- 17205669
TI  - Experiences of Maori families accessing health care for their unwell children: a
      pilot study.
AB  - The aim of this study was to explore with a small number of Maori families their
      experiences of accessing health care when their children were unwell with a
      respiratory condition. Although there is a wide variety of literature exploring
      Maori and their ability to access health care, there is a very limited amount
      that describes the experience of individual Maori families in accessing health
      care for their children. A qualitative research methodology was used in the
      study. Participating families were among those experiencing an admission to a
      children's ward between July and December 2003. Four families were interviewed.
      They discussed in depth their experience of accessing health care for their
      unwell children. Data were analysed using thematic analysis, and three common
      themes were evident: family resources, choice of health service provider and
      parents' feelings of vulnerability. The findings highlight that while socio
      economic status plays a large part in determining the ease with which families
      can access the needed health care, there are other barriers within the health
      system which also pose difficulties for Maori.

PMID- 17205670
TI  - Protein misassembly: macromolecular crowding and molecular chaperones.
AB  - The generic tendency of proteins to misassemble into nonfunctional, and sometimes
      cytotoxic, structures poses a universal problem for all types of cell. This
      problem is exacerbated by the high total concentration of macromolecules found
      within most intracellular compartments but it is solved by the actions of
      molecular chaperones. This review discusses some of the basic evidence and key
      concepts relating to this conclusion.

PMID- 17205671
TI  - The cellular "networking" of mammalian Hsp27 and its functions in the control of
      protein folding, redox state and apoptosis.
AB  - Cells possess effective mechanisms to cope with chronic or acute disturbance of
      homeostasis. Key roles in maintaining or restoring homeostasis are played by the
      various heat shock or stress proteins (Hsps). Among the Hsps, the group of
      proteins characterized by low molecular masses (between 20 to 30 kDa) and
      homology to alpha-crystallin are called small stress proteins (denoted sHsps).
      The present chapter summarizes the actual knowledge of the protective mechanisms
      generated by the expression of mammalian Hsp27 (also denoted HspB1 in human)
      against the cytotoxicity induced by heat shock and oxidative stress. It also
      describes the anti-apoptotic properties of Hsp27 and their putative consequences
      in different pathological conditions.

PMID- 17205672
TI  - Molecular interaction network of the Hsp90 chaperone system.
AB  - Hsp90 is an essential and ubiquitous molecular chaperone that is required for the
      proper folding of a set of client proteins at a late stage in their folding
      process. In eukaryotes, cytoplasmic Hsp90 is absolutely essential for cell
      viability under all growth conditions. The functional cycle of the Hsp90 system
      requires a cohort of cochaperones and cofactors that regulate the activity of
      this chaperone. Hence, Hsp90 function is highly complex; in order to understand
      that complexity, several groups have attempted to map out the interaction network
      of this chaperone in yeast and mammalian systems using the latest available
      proteomic and genomic tools. Interaction networks emerging from these large scale
      efforts clearly demonstrate that Hsp90 plays a central role effecting multiple
      pathways and cellular processes. In yeast Saccharomyces cerevisiae, Hsp90 was
      shown to interact directly or indirectly with at least 10% of the yeast ORFs. The
      systematic application of large scale approaches to map out the Hsp90 chaperone
      network should allow the determination of the mechanisms employed by this
      chaperone system to maintain protein homeostasis in the cell.

PMID- 17205673
TI  - Organization of the functions and components of the endoplasmic reticulum.
AB  - The endoplasmic reticulum is the site of entry into the secretory pathway and
      represents a major and particularly crowded site of protein biosynthesis. In
      addition to the complexity of protein folding in any organelle, the ER
      environment poses further dangers and constraints to the process. A quality
      control apparatus exists to monitor the maturation of proteins in the ER. Nascent
      polypeptide chains are specifically prevented from traveling further along the
      secretory pathway until they have completed their folding or assembly. Proteins
      that cannot achieve a proper conformation are recognized and removed from the ER
      for degradation by the 26S proteasome. Finally, the homeostasis of the ER is
      vigilantly monitored and changes that impinge upon the proper maturation of
      proteins in this organelle lead to the activation of a signal transduction
      cascade that serves to restore balance to the ER. Recent studies suggest that
      some of these diverse functions may be achieved due to the organization of the ER
      into functional and perhaps even physical sub-domains.

PMID- 17205674
TI  - Molecular crime and cellular punishment: active detoxification of misfolded and
      aggregated proteins in the cell by the chaperone and protease networks.
AB  - Labile or mutation-sensitised proteins may spontaneously convert into aggregation
      prone conformations that may be toxic and infectious. This hazardous behavior,
      which can be described as a form of "molecular criminality", can be actively
      counteracted in the cell by a network of molecular chaperone and proteases.
      Similar to law enforcement agents, molecular chaperones and proteases can
      specifically identify, apprehend, unfold and thus neutralize "criminal" protein
      conformers, allowing them to subsequently refold into harmless functional
      proteins. Irreversibly damaged polypeptides that have lost the ability to
      natively refold are preferentially degraded by highly controlled ATP-consuming
      proteases. Damaged proteins that escape proteasomal degradation can also be
      "incarcerated" into dense amyloids, "evicted" from the cell, or internally
      "exiled" to the lysosome to be hydrolysed and recycled. Thus, remarkable
      parallels exist between molecular and human forms of criminality, as well as in
      the cellular and social responses to various forms of crime. Yet, differences
      also exist: whereas programmed death is the preferred solution chosen by aged and
      aggregation-stressed cells, collective suicide is seldom chosen by lawless
      societies. Significantly, there is no cellular equivalent for the role of
      familial care and of education in general, which is so crucial to the proper
      shaping of functional persons in the society. Unlike in the cell, humanism
      introduces a bias against radical solutions such as capital punishment, favouring
      crime prevention, reeducation and social reinsertion of criminals.

PMID- 17205675
TI  - Chaperones as parts of cellular networks.
AB  - The most important interactions between cellular molecules have a high affinity,
      are unique and specific, and require a network approach for a detailed
      description. Molecular chaperones usually have many first and second neighbors in
      protein-protein interaction networks and they play a prominent role in signaling
      and transcriptional regulatory networks of the cell. Chaperones may uncouple
      protein, signaling, membranous, organellar and transcriptional networks during
      stress, which gives an additional protection for the cell at the network-level.
      Recent advances uncovered that chaperones act as genetic buffers stabilizing the
      phenotype of various cells and organisms. This chaperone effect on the emergent
      properties of cellular networks may be generalized to proteins having a specific,
      central position and low affinity, weak links in protein networks. Cellular
      networks are preferentially remodeled in various diseases and aging, which may
      help us to design novel therapeutic and anti-aging strategies.

PMID- 17205676
TI  - Chaperones as parts of organelle networks.
AB  - The efficiency, divergence, and specificity of virtually all intracellular
      metabolic and signalling pathways largely depend on their compartmentalized
      organization. A corollary of the requirement of compartmentalization is the
      dynamic structural partition of the intracellular space by endomembrane systems.
      A branch of these membranes communicate with the extracellular space through the
      endo- and exocytotic processes. Others, like the mitochondrial and endoplasmic
      reticulum networks accomplish a further role, being fundamental for the
      maintenance of cellular energy balance and for determination of cell fate under
      stress conditions. Recent structural and functional studies revealed that the
      interaction of these networks and the connectivity state of mitochondria controls
      metabolic flow, protein transport, intracellular Ca2+ signalling, and cell death.
      Moreover, reflecting the fact that the above processes are accomplished in a
      microdomain between collaborating organelle membranes, the existence of
      macromolecular complexes at their contact sites have also been revealed. Being
      not only assistants of nascent protein folding, chaperones are proposed to
      participate in assembling and maintaining the function of the above complexes. In
      this chapter we discuss recently found examples of such an assembly of protein
      interactions driven by chaperone proteins, and their role in regulating
      physiological and pathological processes.

PMID- 17205677
TI  - Heat shock factor 1 as a coordinator of stress and developmental pathways.
AB  - The transition from normal growth conditions to stressful conditions is
      accompanied by a robust upregulation of heat shock proteins, which dampen the
      cytotoxicity caused by misfolded and denatured proteins. The most prominent part
      of this transition occurs on the transcriptional level. In mammals, protein
      damaging stress leads to the activation of heat shock factor 1 (HSF1), which
      binds to upstream regulatory sequences in the promoters of heat shock genes. The
      activation of HSF1 proceeds through a multi-step pathway, involving a monomer-to
      trimer transition, nuclear accumulation and extensive posttranslational
      modifications. In addition to its established role as the main regulator of heat
      shock genes, new data link HSF 1 to developmental pathways. In this chapter, we
      examine the established stress-related functions and prospect the intriguing role
      of HSF 1 as a developmental coordinator.

PMID- 17205678
TI  - Chaperone regulation of the heat shock protein response.
AB  - The heat shock protein response appears to be triggered primarily by nonnative
      proteins accumulating in a stressed cell and results in increased expression of
      heat shock proteins (HSPs). Many heat shock proteins prevent protein aggregation
      and participate in refolding or elimination of misfolded proteins in their
      capacity as chaperones. Even though several mechanisms exist to regulate the
      abundance of cytosolic and nuclear chaperones, activation of heat shock
      transcription factor 1 (HSF1) is an essential aspect of the heat shock protein
      response. HSPs and co-chaperones that are assembled into multichaperone complexes
      regulate HSF1 activity at different levels. HSP90-containing multichaperone
      complexes appear to be the most relevant repressors of HSF1 activity. Because
      HSP90-containing multichaperone complexes interact not only specifically with
      client proteins including HSF1 but also generically with nonnative proteins, the
      concentration of nonnative proteins influences assembly on HSF1 of HSP90
      containing complexes that repress activation, and may play a role in
      inactivation, of the transcription factor. Proteins that are unable to achieve
      stable tertiary structures and remain chaperone substrates are targeted for
      proteasomal degradation through polyubiquitination by co-chaperone CHIP. CHIP can
      activate HSF1 to regulate the protein quality control system that balances
      protection and degradation of chaperone substrates.

PMID- 17205679
TI  - Mechanisms of activation and regulation of the heat shock-sensitive signaling
      pathways.
AB  - Heat shock (HS), like many other stresses, induces specific and highly regulated
      signaling cascades that promote cellular homeostasis. The three major mitogen
      activated protein kinases (MAPK) and protein kinase B (PKB/Akt) are the most
      notable of these HS-stimulated pathways. Their activation occurs rapidly and
      sooner than the transcriptional upregulation of heat shock proteins (Hsp), which
      generate a transient state of extreme resistance against subsequent thermal
      stress. The direct connection of these signaling pathways to cellular death or
      survival mechanisms suggests that they contribute importantly to the HS response.
      Some of them may counteract early noxious effects of heat, while others may
      bolster key apoptosis events. The triggering events responsible for activating
      these pathways are unclear. Protein denaturation, specific and nonspecific
      receptor activation, membrane alteration and chromatin structure perturbation are
      potential initiating factors.

PMID- 17205680
TI  - Membrane-regulated stress response: a theoretical and practical approach.
AB  - Anumber of observations have lent support to a model in which thermal stress is
      transduced into a signal at the level of the cellular membranes. Our alternative,
      but not exclusive, approach is based on the concept that the initial stress
      sensing events are associated with the physical state and lipid composition of
      cellular membranes, i.e., the subtle alteration(s) of membrane fluidity, phase
      state, and/or microheterogeneity may operate as a cellular thermometer. In fact,
      various pathological states and aging are associated with typical "membrane
      defects" and simultaneous dysregulation of heat shock protein synthesis. The
      discovery of nonproteotoxic membrane-lipid interacting compounds, capable of
      modulating membrane microdomains engaged in primary stress sensing may be of
      paramount importance for the design of new drugs with the ability to induce or
      attenuate the level of particular heat shock proteins.

PMID- 17205681
TI  - Beyond the lipid hypothesis: mechanisms underlying phenotypic plasticity in
      inducible cold tolerance.
AB  - The physiological adjustment of organisms in response to temperature variation is
      a crucial part of coping with environmental stress. An important component of the
      cold response is the increase in membrane lipid unsaturation, and this has been
      linked to an enhanced resistance to the debilitating or lethal effects of cold.
      Underpinning the lipid response is the upregulation of fatty acid desaturases
      (des), particularly those introducing double bonds at the 9-10 position of
      saturated fatty acids. For plants and microbes there is good genetic evidence
      that regulation of des genes, and the consequent changes in lipid saturation, are
      causally linked to generation of a cold-tolerant phenotype. In animals, however,
      supporting evidence is almost entirely limited to correlations of saturation with
      cold conditions. We describe our recent attempts to provide a direct test of this
      relationship by genetic manipulation of the nematode Caenorhabditis elegans. We
      show that this species displays a strong cold tolerant phenotype induced by prior
      conditioning to cold, and that this is directly linked to upregulated des
      activity. However, whilst genetic disruption of des activity and lipid
      unsaturation significantly reduced cold tolerance, animals retained a substantial
      component of their stress tolerant phenotype produced by cold conditioning. This
      indicates that mechanisms other than lipid unsaturation play an important role in
      cold adaptation.

PMID- 17205682
TI  - Trehalose as a "chemical chaperone": fact and fantasy.
AB  - Trehalose is a disaccharide of glucose that is found at high concentrations in a
      wide variety of organisms that naturally survive drying in nature. Many years ago
      we reported that this molecule has the remarkable ability to stabilize membranes
      and proteins in the dry state. A mechanism for the stabilization rapidly emerged,
      and it was sufficiently attractive that a myth grew up about trehalose as a
      universal protectant and chemical chaperone. Many of the claims in this regard
      can be explained by what is now known about the physical properties of this
      interesting sugar. It is emerging that these properties may make it unusually
      useful in stabilizing intact cells in the dry state.

PMID- 17205683
TI  - Chaperones as part of immune networks.
AB  - Network theory is increasingly accepted as a basic regulatory mechanism in
      diverse immunological functions. Heat shock proteins (Hsps) are involved in
      multiple networks in the immune system. Hsps themselves (foreign or endogenous)
      activate innate immunity and play important roles to deliver self or nonself
      materials to antigen presenting cells. However, Hsps are immunodominant antigens
      during infectious diseases making self Hsps endangered targets of autoimmunity by
      cross-reactive clones. Therefore, it is not surprising that the mechanism of
      protection of self Hsps is not clonal deletion in natural self tolerance; rather,
      self Hsps are protected by active regulating natural autoimmunity. The active
      regulatory/protective immunity is accomplished by natural autoantibodies and
      regulatory T cells, both recognizing Hsps. The multiple involvements of Hsps in
      immune networks make them ideal targets of therapy in autoimmune diseases.
      Indeed, immunotherapy with Hsps was recently reported to be effective treatment
      modality against cancer, arthritis or diabetes mellitus.

PMID- 17205684
TI  - The stress of misfolded proteins: C. elegans models for neurodegenerative disease
      and aging.
AB  - A growing number of human neurodegenerative diseases are associated with the
      expression of misfolded proteins that oligomerize and form aggregate structures.
      Over time, accumulation of misfolded proteins leads to the disruption of cellular
      protein folding homeostasis and eventually to cellular dysfunction and death. To
      investigate the relationship between misfolded proteins, neuropathology and
      aging, we have developed models utilizing the nematode C. elegans. In addition to
      being genetically tractable, C. elegans have rapid growth rates and short life
      cycles, providing unique advantages for modeling neurodegenerative diseases of
      aging caused by the stress of misfolded proteins. The C. elegans models described
      here express polyglutamine expansion-containing proteins, as occur in
      Huntington's disease. Through the use of tissue-specific expression of different
      lengths of fluorescently tagged polyglutamine repeats, we have examined the
      dynamics of aggregate formation both within individual cells and over time
      throughout the lifetime of individual animals, identifying aging and other
      genetic modifiers as an important physiologic determinant of aggregation and
      toxicity.

PMID- 17205685
TI  - Hsp90 and developmental networks.
AB  - The most abundant cytoplasmic chaperone of eukaryotic cells, Hsp90 is a hub in
      developmental regulatory networks and the first example described of the
      phenomenon of molecular buffering. As a chaperone for many different signaling
      proteins, Hsp90 maintains the clarity and strength of communication within and
      between cells, concealing developmental and stochastic variations that otherwise
      cause abrupt morphological changes in a large variety of organisms, including
      Drosophila and Arabidopsis. The chapter provides a framework for understanding
      how Hsp90 controls the sudden appearance of novel morphologies. We start with a
      discussion of the longstanding problem of hidden polygenic variation and then
      introduce the idea of signal transduction thresholds in mediating the effect of
      Hsp90 on the expression of phenotypic variation. This leads to a discussion of
      the role of nonlinearity in creating thresholds for sudden changes in cellular
      responses to developmental signals. We end with speculation on the potentially
      pivotal role of Hsp90 in controlling the developmental networks that determine
      morphological stasis and change in evolution.

PMID- 17205686
TI  - [Molecular analysis of vancomycin-resistant enterococci isolated from clinical
      samples].
AB  - Enterococcus species are the inhabitants of gastrointestinal flora and can cause
      endocarditis, urinary tract infections, and bacteremia. In recent years,
      infections caused by vancomycin-resistant enterococci (VRE) have increased in our
      country. The infections caused by VRE are treated with glycopeptide antibiotics
      like vancomycin and teicoplanin. Although seven different resistant genes have
      been described in VRE, VanA is the most frequently detected one in Turkey. The
      aim of this study was (i) to genotype four vancomycin-resistant Enterococcus
      faecium strains isolated in our hospital, by using pulsed field gel
      electrophoresis (PFGE); and (ii) to detect the type of Van gene by using
      polymerase chain reaction. Three of the strains were isolated from blood cultures
      and one from cerebrospinal fluid of the hospitalized patients between the years
      2000-2004, and identified by both conventional methods and commercial kits. By
      using PFGE, we detected that isolates were different according to Tenover
      criteria and they had VanA genes. As a result, VanA carrying VRE cause sporadic
      infections in our hospital. The molecular epidemiologic investigation of
      resistant microorganisms is important in terms of infection control and
      epidemiology.

PMID- 17205687
TI  - [Isolation and identification of Burkholderia cepacia complex from cystic
      fibrosis patients].
AB  - In this study, sputum samples collected from cystic fibrosis patients with
      preliminary diagnosis of pulmonary infection were evaluated for the presence of
      bacteria belonging to Burkholderia cepacia complex by commercial phenotypic
      systems and recA polymerase chain reaction (PCR). A total of 85 patients ages
      between 5-30 years (mean age: 12.8 years) were included to the study with
      female/male ratio of 44/41. The mostly isolated bacteria from 85 sputum samples
      were found as Staphylococcus aureus (55.3%), Pseudomonas aeruginosa (48.2%) and
      Haemophilus influenzae (15.3%), whereas B. cepacia complex was phenotypically
      identified from two (2.3%) out of the samples. However only one was confirmed by
      PCR and typed as Burkholderia multivorans by restriction fragment lenght
      polymorphism method. This study emphasizes the importance of molecular methods as
      confirmatory tests for accurate identification of B. cepacia complex.

PMID- 17205688
TI  - [Investigation of the role of ribonuclease L gene in the response of tonsil
      tissues against viral infections].
AB  - Mutations or variants that impair function of ribonuclease L (RNase-L),
      particularly R462Q, have been proposed as susceptibility factors for the innate
      antiviral response. The aim of this study was to investigate and compare the
      expression levels of RNase-L and mutation of R462Q in the tonsils of
      tonsillectomy patients who were infected and not infected with herpes simplex
      virus type 1 (HSV-1), Epstein-Barr virus (EBV) and human herpes virus 6 (HHV-6).
      Six tonsils were included in the study. One tonsil was infected with all of these
      three viruses, two were infected with at least one of these viruses, and three
      were not infected with these viruses. The presence of viral DNAs in the tonsil
      tissues had been searched by polymerase chain reaction (PCR) in our previous
      study. Reverse transcriptase PCR method was used for RNase-L expression analyses,
      and single strand conformation polymorphism (SSCP) and direct sequencing methods
      were used for the mutation analyses. PCR products containing R462Q mutation site
      in the genomic DNA were used for SSCP analysis. In addition to SSCP analyses,
      partial sequencing of the cDNA PCR product containing R462Q mutation site were
      performed. As a result, no difference between the virus-infected and non-infected
      tonsils for the expressions of RNase-L were detected, and there were no mutations
      detected by SSCP and sequencing analyses. It was concluded that other factors
      than RNase-L protein, might be involved in the innate defense mechanisms of
      tonsil cells against viruses.

PMID- 17205689
TI  - [Investigation of the efficacy of electrolyzed acid water on the standard strains
      of some pathogenic microorganisms].
AB  - Many of the studies have indicated that electrolyzed acid water (EAW) has a
      strong microbicidal activity. In this study, EAW was obtained by the exposure of
      NaCl (10 g/L) and tap water mixture to direct electric current (2 ampere) during
      15 minutes, in an instrument designed by the study group. EAW was tested for its
      inactivation efficacy on the standard strains of Staphylococcus aureus, Candida
      albicans and Pseudomonas aeruginosa in different concentrations and for different
      periods (0, 10, 30 and 60 seconds). The EAW dilutions were prepared by using
      sterile deionized water in the rates of 100% (undiluted), 20%, 10%, 5%, 2% and
      1%, while deionized water alone was used as control. The oxidation-reduction
      potency, pH, and free cloride amounts were separately measured in different
      concentrations of EAW. UNE-EN 1276 standard was used to investigate the
      inhibitory efficacy of EAW on S. aureus ATCC 29213, C. albicans ATCC 10231 and P.
      aeruginosa ATCC 9027 through the use of membrane filtration method. As a result,
      all of the microorganisms have been completely inactivated at the end of 10th
      second, in all of the EAW concentrations, except 1% dilution. However, after the
      treatment with 1% EAW during 60 seconds, it was determined that an average
      population of 4.09 log cfu/ml, 4.56 log cfu/ml, and 3.62 log cfu/ml survived,
      respectively for S. aureus, C. albicans and P. aeruginosa. Our data showed that
      2% concentration of EAW had a bactericidal effect and may be used for the surface
      disinfection in practice.

PMID- 17205690
TI  - [Histologic demonstration of adrenal macrophages as a member of mononuclear
      phagocytic system in guinea pig models].
AB  - Macrophages as mononuclear phagocytes, function in removing foreign substances
      and in the initiation of the immune response. Although some tissue-specific
      macrophages such as Kupffer's cells and alveolar macrophages are well-known, any
      knowledge about the adrenal macrophages are not yet documented in the textbooks.
      The aim of this study was to demonstrate the resident macrophages in the adrenals
      of a total 16 (8 pregnant, 8 non-pregnant) guinea pigs. Four of the animals were
      injected with India ink (no intervention for the other animals), and after
      sacrificing all animals, removed adrenals were fixed in Bouin's solution, and
      embedded in paraffin. Sections were stained with haematoxylin-eosin (HE) and
      periodic acid-Schiff (PAS) methods. Many macrophages with yellowish-brown
      cytoplasm in HE slides, especially adjacent to sinusoids, were observed primarily
      in the zona reticularis, suggesting that they are rich in lipofuscin pigment.
      These cells were also PAS positive. Adrenals of India ink-injected animals
      demonstrated perisinusoidal macrophages phagocytosing the ink. Much more adrenal
      macrophages were seen in the pregnant animals in comparison with the non
      pregnants. It has been previously reported that the number of human macrophages
      increases with rising concentrations of estrogen during pregnancy. Thus, higher
      number of adrenal macrophages in pregnant animals was an expected result. Since
      they secrete cytokines, macrophages are favorable cells in terms of interactions
      of the neuro-endocrine organs with the immune system. Some cytokines released by
      macrophages have been stated to induce adrenocortical steroidogenesis independent
      from adrenocorticotropic hormone through medullary catecholamines. Thus,
      macrophages may have a significant role in the immune-adrenocortical
      communications within the adrenal. Finally, resident macrophages of the adrenals
      wait to be documented in the textbooks.

PMID- 17205691
TI  - [Evaluation of specialist training in basic sciences in two university medical
      schools: perspectives from both specialist residents and trainers].
AB  - A questionnaire survey has been undertaken to evaluate the specialist training in
      basic sciences in view of both specialist residents (SpRs) and trainers of two
      university medical schools in Izmir, Turkey. Seventy four SpRs (39 from Dokuz
      Eylul and 35 from Ege Universities) and 15 basic science units (8 from Dokuz Eyul
      and 7 from Ege Universities) were joined in this survey. The response rate was
      73% for SpRs and 86.7% for basic science units. Technical equipments, the number
      of trainers, education programmes and training equipments of basic science units
      have been found adequate both by SpRs and trainers. However, professional
      education has been found incapable. In basic science units, it was seen that the
      SpRs are permanently assessed and attended the investigation activities during
      educational process. The trainers expressed that the SpRs have got training
      knowledge, skills and attitute sufficiently, but SpRs answered that they have got
      them in moderate means. In conclusion, although the training programmes of SpRs
      in both of the university hospitals have been found competent, SpRs indicated
      that there is a need for development of trainers quality, assessing methods and
      rotational education programmes in basic science.

PMID- 17205692
TI  - [Evaluation of the level of knowledge of medical secretaries about clinical
      specimens].
AB  - The rapid development of medical industry in the last 5 years in Turkey led to an
      increased demand for medical technicians and secretaries. The aim of this study
      was to evaluate the level of knowledge of students in Occupational School of
      Medical Documentation and Secretary about the clinical specimens, and to estimate
      the need for an additional education on clinical specimens. Four hundred and
      forty eight students from eight universities were participated to this
      questionnaire survey. Mean age of the participants were 20.4+/-1.66 years and 342
      (76.3%) of them were female students. The mean answer rate of students to the
      questions about clinical specimens was found 3.4+/-1.9% (min-max: 0-10). Correct
      answer rates were similar for both first and second year students. There was a
      negative relationship between the educational year and the rate of correct
      answer, however the correlation was not significant. Additionally, internship
      period did not have any effect on the level of knowledge. The results of this
      survey have indicated that the level of knowledge of medical secretaries about
      clinical specimens was very low. As the roles and responsibilities of medical
      secretaries in medical industry increases, in order to increase the cost
      effectivity, quality and patient satisfaction, the contents of their education
      programs must be reorganized, and a lecture about clinical specimens should be
      integrated.

PMID- 17205693
TI  - [Short communication: prevalence of extended spectrum beta-lactamases in gram
      negative rods: data of 2001-2004 period].
AB  - This study was undertaken to determine the prevalence of extended spectrum beta
      lactamase (ESBL) production by Gram negative rods (GNRs) isolated from various
      clinical specimens (3.240 urine, 336 pus, 277 feces, 83 blood, 38 sputum) sent to
      our hospital laboratory, between 2001-2004. Of isolated bacteria 71.4% were
      identified as Escherichia coli, 11.1% were Klebsiella spp, 4.2% were Salmonella
      spp, 3.7% were Pseudomonas spp, 3.5% were Proteus spp, 2.9% were Shigella spp,
      2.3% were Enterobacter spp, 0.5% were Acinetobacter spp, 0.12% of each Serratia
      spp, and Stenotrophomonas maltophilia, 0.1% were Citrobacter spp, and one of each
      Providencia spp and Pantoeae spp. (0.02%). ESBL production were screened by using
      the double disk synergy test. Of a total of 3.974 isolates, 269 (6.8%) were found
      to be ESBL producers. Klebsiella spp had the highest rate (14.3%) which was
      followed by Enterobacter spp (8.6%) and E.coli (6.7%). All of the S.maltophilia
      isolates were resistant to carbapenems. One of the Shigella spp was found to be
      an ESBL producer, being the first case from Turkey and the fifth from the world.
      There was statistically significant difference in distribution of ESBL producing
      isolates between hospitalized (16%) and non-hospitalized patients (5%) (p<0.01).
      A significant increase in ESBL production rates (from 3.8% in 2001 to 10.6% in
      2004) was observed over time (p<0.05). The increasing trend (about 300% in four
      years) in ESBL production rates, should be considered as an indicator for
      expansion propensity and speed of the threat against the effective treatment of
      infections, and possible preventive strategies should be established.

PMID- 17205694
TI  - [Short communication: comparison of two different assays for the investigation of
      HBsAG, anti-HCV and anti-HIV in blood donors].
AB  - Acquisition of infectious agents during blood transfusions is an important
      complication. The choice of screening tests is of crucial importance since it is
      difficult to detect the markers of the infection in blood donors, especially
      before the window period when seroconversion has not taken place. In this study
      the blood samples of 150 volunteer donors were screened for anti-HIV 1/2, anti
      HCV, and HBsAg by chemiluminescence method. Samples found to be positive for anti
      HIV 1/2 and anti-HCV were confirmed by Western Blot and Inno-Lia HCV Ab III
      tests, respectively. HBsAg, anti-HCV and anti-HIV 1/2 antibodies were also
      investigated by the Simul-Tec immunoassay in all of the samples, and the results
      were compared. As a result, 4.7% of the donors were positive for HBsAg and
      confirmatory tests showed that the positivity rate was 2.7% for anti-HCV, 0.7%
      for anti-HIV 1/ 2. Although the results obtained with the Simul-Tec immunoassay
      were similar to the screening test results obtained for HBsAg, discrepant results
      were obtained for anti-HCV and anti-HIV 1/ 2. The results of this study indicated
      that Simul-Tec immunassay method is not yet ready to meet the demands in terms of
      anti-HCV and anti-HIV detection.

PMID- 17205695
TI  - [Short communication: hepatitis B, hepatitis C and human immunodeficiency virus
      seropositivities in women admitted to Sanliurfa Gynecology and Obstetrics
      Hospital].
AB  - The aim of this retrospective study was to determine the seroprevalence of
      hepatitis B virus (HBV), hepatitis C virus (HCV) and immune deficiency virus
      (HIV) in women who were admitted to Sanliurfa Gynecology and Obstetrics Hospital
      clinics and to compare the results with the previous seropositivity rates
      reported from different regions of Turkey. The serum samples were screened for
      HBsAg, anti-HCV and anti-HIV markers by a commercial chemiluminescence method
      (UniCel Dxl 800, Beckman Coulter, USA), during a six months period (January 1st
      to June 30th, 2006). As a result the seropositivity rates of HBsAg, anti-HCV and
      anti-HIV were found as 5.1% (119/2335), 0.9% (18/2066) and 0.1% (3/2548),
      respectively. While anti-HCV seropositive results were approved by confirmation
      tests, three of anti-HIV positive results were not confirmed and accepted as
      false positivities. HBsAg, anti-HCV and anti-HIV seropositivities detected in our
      study were similar to the rates previously reported in other studies in Turkey.
      However, HBsAg positivity was found slightly higher than the rates that were
      reported from western parts of our country. This result may be related to the
      lower socioeconomical status of Sanliurfa (which is located in Southeast
      Anatolia), and indicates that HBV should be considered as a serious public health
      problem in East and Southeast parts of Turkey.

PMID- 17205696
TI  - [Short communication: investigation of Toxoplasma gondii antibodies in blood
      donors by Sabin-Feldman Dye Test].
AB  - In this study, a serological survey of Toxoplasma gondii infection in healthy
      blood donors admitted to Blood Center of Ministry of Health, Ankara Training and
      Research Hospital was carried out. Sera from 390 male and 24 female (ages between
      18-59 years) were evaluated by using Sabin Feldman Dye Test (SFDT). Of 414 donors
      176 (42.5%) were found positive for T. gondii antibodies. Among the seropositive
      cases, 106 (25.6%) had 1/16, 40 (9.7%) had 1/64, 28 (6.8%) had 1/256, and two
      (0.5%) had 1/1024 SFDT titers. The seropositivity rates for females and males
      were found as 62.5% and 41.3%, respectively, and there was no statistically
      significant difference (p=0.053). A statistically significant increase was
      detected in the seropositivity rates with age, 39% being under the age of 40 (18
      39 years), 54% over the age of 40 (p<0.01). In conclusion, although it is not
      necessary to screen the blood donors routinely for T. gondii antibodies, if the
      transfusion of cellular blood components is planned for immunosuppresive
      recipients, then those bloods should be tested for T. gondii antibodies.

PMID- 17205697
TI  - [Short communication: prevalence of fungal allergy in patients applied to
      hospital with symptoms of atopic disease in Kocaeli, Turkey].
AB  - The aim of this study was to investigate the prevalence of fungal sensitization
      and to detect the IgE and eosinophilic cationic protein (ECP) levels in the
      positive cases inhabiting in Kocaeli province (located in Northwest region of
      Turkey). The results of mixed fungus tests of 1.799 patients (870 male, 929
      female) ages between 3-80 years old who were admitted to Kocaeli University
      Medical Faculty Hospital in the period of January 2002-January 2005, with the
      symptoms of atopic disease such as upper/lower respiratory tract symptoms, asthma
      and/or rhinitis and/or eczema, were evaluated retrospectively. Serum IgE and ECP
      levels of all cases were determined by a commercial enzyme immunoassay (UniCAP
      System, Pharmacia, Uppsala, Sweden) method. The allergy test performed by using
      mixed fungal panel (Penicillium notatum, Cladosporium herbarum, Aspergillus
      fumigatus, Candida albicans, Alternaria alternata, Helminthosporium halodes) was
      found positive in 68 cases (3.8%). Of those cases 7 (10.2%) were found to be
      sensitized to Alternaria alternata, 8 (11.7%) to Aspergillus fumigatus, 10
      (14.7%) to Penicillium notatum, and 6 (8.8%) were sensitized to more than one
      fungus. The mean IgE (106.2+/-166.1) and ECP levels (31.7+/-18.3) of fungus
      sensitized cases were found significantly higher than the non-sensitized subjects
      (IgE; 77.8+/-95.0, ECP; 22.4+/-16.5) (p<0.001). The prevalence rates of fungal
      allergy in our region were determined as 1.9% (26/1.341), 4.5% (2/44) and 9.6%
      (40/414) in pediatric, adolescent and adult populations, respectively. In
      conclusion, it was determined that the rate of the sensitization against fungi
      was low in Kocaeli, Turkey and it exhibited a tendency towards increase with age.

PMID- 17205698
TI  - [Liver abscess and infective endocarditis cases caused by Ruminococcus
      productus].
AB  - The genus Ruminococcus which are anaerobe Gram positive cocci, previously
      classified as Peptostreptococcus, may colonize the upper respiratory tract,
      gastrointestinal tract, vagina and skin of humans and animals. In this report a
      case of liver abscess and a case of infective endocarditis caused by Ruminoccocus
      productus, which is very rarely encountered in the clinical practice were
      presented. The first case was a 32 years old male who was admitted to the
      hospital in 2002, with the complaints of fever lasting for 20 days and pain while
      breathing. The abdominal ultrasonography revealed the presence of a liver
      abscess, and the drainage material from the abscess yielded Ruminococcus
      productus, identified in BACTEC 9200 (Becton Dickinson, Sparks, Md) anaerobe
      system. As the isolate was found to be sensitive to penicilin, the empirical
      gentamicin and ampicillin/sulbactam therapy was continued. The second case was a
      25 years old male who was admitted to the hospital in 2005, with the signs of
      fever lasting for 3-4 months, chills, bone and joint pains. As multiple
      vegetations were detected in echocardiography, blood cultures were collected and
      empirical therapy with ceftriaxone and gentamicin was initiated with the
      preliminary diagnosis of infective endocarditis. Bacteria which were isolated
      from blood cultures by BACTEC 9200 system have been identified as R. productus.
      As this strain was also sensitive to penicillin, the empirical therapy was
      changed to penicilin and gentamicin. These two cases indicated that R. productus
      should be considered in complicated infections even if it is a rarely isolated
      species from the clinical samples.

PMID- 17205699
TI  - [Catheter associated Staphylococcus sciuri sepsis in a patient with acute myeloid
      leukemia].
AB  - The coagulase-negative bacterial species Staphylococcus sciuri is widely
      distributed in the natural environment. Although principally found in animals, S.
      sciuri is occasionally isolated from human samples. In this paper, S. sciuri
      bacteremia which was associated with an indwelling catheter of a patient with
      acute myeloid leukemia (AML) and neutropenia was presented. An empirical
      intravenous antibiotic therapy (meropenem, vancomycin) was initiated with the
      preliminary diagnosis of febrile neutropenia and catheter infection. The catalase
      and oxidase positive, tube coagulase negative strain isolated from three of the
      concurrent blood cultures and intravenous catheter culture has been identified as
      S. sciuri. The isolate was found resistant to penicilin and oxacilline. This case
      has emphasized the importance of identification of coagulase-negative
      staphylococci isolated from the cultures of patients with haematological
      malignancy.

PMID- 17205700
TI  - [An atypical measles case presenting with severe cervical spasm].
AB  - Atypical measles is characterized by high fever, headache, myalgia and atypical
      rash, in patients who were vaccinated against measles. In this report a 22 years
      old male patient presenting with severe cervical and shoulder muscles spasms,
      purpuric and petechial lesions on palm, sole and whole body, has been presented.
      The patient had not an underlying disease or immunosuppression, and he had
      experienced single dose of measles vaccine when he was nine months old. Diagnosis
      of atypical measles was based on the clinical and serological findings (by
      measles IgM and IgG positivity). The aim of the presentation of this case was to
      emphasize that atypical measles should be considered for differential diagnosis
      in the cases complaining of muscle spasms and atypical skin rashes even if
      vaccinated against measles.

PMID- 17205701
TI  - [A plasmodium alciparum malaria case originated from Mozambique: clues for the
      diagnosis and therapy].
AB  - The aim of this report was the presentation of a falciparum malaria case
      originated from Mozambique and the evaluation of diagnostic and therapeutic
      approaches. Sixty years old Canadian male patient who has been working in
      Mozambique for 13 years was admitted to hospital with the complaints of high
      fever (39.6 degrees C), weakness, nausea and vomiting, when returned to Turkey.
      The patient was sleepiness and has undulating confusions with the laboratory
      findings of thrombocytopenia, hypoglycemia, hyperlactatemia, increased
      BUN/creatinine levels, increased LDH levels and hypocholesterolemia. The
      diagnosis was based on the detection of multiple ring formed trophozoites in the
      thick blood film and the presence of multiple ring forms inside the erythrocytes
      and the absence of trophozoite and shizont forms in the thin blood film. His
      medical history revealed that he experienced another falciparum malaria infection
      one year ago, although he has been using mefloquine prophylaxis during his stay
      in Mozambique. Since chloroquine resistance was thought to be high in this
      region, the patient was treated with quinine sulphate and doxycycline. Six days
      after the onset of therapy, the biochemical markers turned to normal and 14 days
      later the blood films were free of the parasite. The patient was given
      doxycycline prophylaxis since he would return to Mozambique. In conclusion, the
      followings should be taken into consideration for the diagnosis and therapy: (i)
      cyclic type of fever which is characteristic for malaria, might not be detected
      in falciparum malaria; (ii) some of the clinical symptoms might be blocked by
      partial immune response in case of recurrent infections; (iii) thrombocytopenia
      and hypocholesterolemia might indicate the presence of falciparum malaria; and
      when falciparum malaria is confirmed by parasitological examinations the patient
      should be treated as if he/she is accepted as resistant to chloroquine.

PMID- 17205702
TI  - [Herpes simplex virus vaccine studies: from past to present].
AB  - The dramatical increase in the prevalence of Herpes simplex virus (HSV)
      infections and the significant physical and psychosocial morbidity of HSV type 2
      infections, generate the need for an efficacious HSV vaccine. The most important
      properties of HSVs that should be targeted for a successful vaccine are neuronal
      invasion, latency and reactivation in spite of specific host immune responses.
      The major expectation for an ideal HSV vaccine candidate is to induce sterilizing
      immunity, which must be effective at all portals of HSV entry; to prevent or
      reduce the symptomatic disease and to eliminate or at least to limit the
      asymptomatic viral shedding. The first vaccine studies have began in the 1920s
      and in the intervening eight decades there have been many attempts to develop an
      effective one. Although encouraging findings came from experiments in various
      animal models, human studies have been disappointing, unfortunately. The vaccine
      strategies that have undergone clinical evaluation until today included
      autoinoculation of live HSV, whole inactivated vaccines, attenuated live virus
      vaccines, modified live virus subunit vaccines, cell culture-derived subunit
      vaccines, recombinant subunit (glycoprotein) vaccines, DISC (Disabled Infectious
      Single Cycle) virus vaccines, viral vectors and naked DNA vaccines. In most of
      the clinical studies the failure of HSV vaccines in spite of inducing very high
      levels of specific neutralizing antibodies have emphasized that cell-mediated
      immune response, especially Thl type immunity is important in preventing both
      primary disease and recurrences with HSV, rather than humoral response. The most
      hopeful result was obtained with HSV-2 gD and alum/MPL vaccine in clinical
      studies. This vaccine was found 74% effective in preventing genital disease in
      HSV seronegative women but was not effective in men or seropositive women. In
      recent years it is possible to genetically engineer HSV to produce a vaccine
      strain that is protective without causing human disease. An example for this
      strategy was the development of a live attenuated vaccine from which
      neurovirulence gene (gamma1 34.5) has been removed. Another promising one was the
      replication-defective DISC virus HSV vaccine which is derived from a virus with
      an essential gene (e.g. gH gene) deleted, so the replication has been limited
      only to a single cycle. As a result, intensive HSV vaccine trials are currently
      underway, although all the previous attempts to produce an effective vaccine for
      the prophylaxis and immunotherapy against HSV have been largely unsuccessful. In
      this review the history of HSV vaccine development together with the preclinical
      and clinical studies from past to present has been summarized and recent progress
      for an effective HSV vaccine together with the further improvements required for
      an immunogenic vaccine have been discussed.

PMID- 17205703
TI  - [The adventure of human immunodeficiency virus: from where to where?].
AB  - What is the origin of HIV as the plaque of our age? What was the way of
      transmission? Did it just cross from the primates to the human being or has it
      been introduced accidentally during the polio vaccine trials period in Africa? Is
      there any other risks in front of the human being, originating from the primates
      harbouring other viruses. In this review article, it has been tried to give up to
      date and scientific answers to these kinds of questions.

PMID- 17205704
TI  - [Distribution of bacteria isolated from urine cultures in Malatya University
      Hospital laboratory (letter)].
AB  - The aim of this letter was to report the distribution of bacterial species
      isolated from the urine samples of patients in Malatya, which is located in
      Estern Anatolia part of Turkey. A total of 3.774 urine cultures were performed in
      the period of April-June 2006, and 792 (21%) of them yielded bacterial growth.
      The isolates have been identified by conventional methods and confirmed by
      Phoenix 100 (Becton-Dickinson) system. As a result, 702 (89%) Gram negative and
      90 (11%) Gram positive bacteria were isolated from the samples. The most
      frequently isolated bacteria were Escherichia coli (58%), followed by Klebsiella
      spp. (14%), Pseudomonas spp. (6.4%), Enterococcus spp. (5%), Staphylococcus spp.
      (3.8%) and Streptococcus spp. (1.7%). The species distribution was found as
      follows; K. pneumoniae ssp pneumoniae (95/110), P. aeruginosa (48/51), E.faecalis
      (27/40), E. cloacae (19/29), P.mirabilis (19/22), C.freundii (8/12), coagulase
      negative staphylococci (19/30) and S. aureus (11/30). The first three array were
      shared by E. coli, Klebsiella spp. and Pseudomonas spp. for the samples of both
      outpatients and inpatients, while Pseudomonas spp. and E. coli were the most
      frequently isolated bacteria from the urine samples of intensive care unit
      patients. Our data was found parallel to the results of other national and
      international studies.

PMID- 17205705
TI  - Effect of modified egg* on developmental defects in neonates of NIDDM induced
      Wistar rats.
AB  - Maternal Zn deficiency has been suggested as the contributing factor for all
      congenital malformations during pregnancy particularly in diabetes. Maternal Zn
      supplementation, therefore, was suggested as one possible nutrition intervention
      during pregnancy to improve its outcome. But a number of trials with Zn
      supplementation are not consistent and discourage the use of excessive Zn
      supplementation during pregnancy. Instead a multivitamin/ mineral supplement to
      them has been suggested to reduce its complication. Accordingly, the poultry egg
      was modified for trace elements, vitamin-E and omega-3 fatty acids so as to use
      it as a dietary supplement for diabetics to reduce their complications during the
      pregnancy. The results showed that NIDDM induced rats fed either on 40 or 80 mg
      Zn/kg diet delivered less number of pups/litter and their body weight was higher
      at birth as compared to control group fed 20 mg Zn/kg diet. During the weaning
      period, some abnormalities characterized by restricted movements of the hind
      legs, curl toes of limbs, eye opening problems, less hair on the body and more
      head to body ratio were observed. Whereas number of pups delivered per litter
      were more with higher body weights without abnormalities in the pups in NIDDM
      groups fed egg mixed diet. Further Zn, Cu and Mg concentrations were
      significantly less in the liver, hair and abdominal muscles in pups in NIDDM
      groups but their concentrations were restored approaching closer to control in
      pups in groups fed egg mixed diet estimated on 18th day of weaning period. The
      excretion of these trace elements increased in the urine of dams fed Zn
      supplemented diet but decreased in the dams fed egg mixed diet on 15th day of
      their suckling period. The data suggest that if these modified eggs are included
      in the regular diet during pregnancy, they may protect the neonates in womb
      against the damaging effect of imbalances of physiologically important nutrients
      due to diabetes or environmental contamination.

PMID- 17205706
TI  - Effect of increased calcium intake on cardiac and vascular Na(+)-K(+)-ATPase
      activity in oral contraceptive-treated female Sprague-Dawley rats.
AB  - The present study aimed at investigating the influence of increased dietary
      calcium on Na(+)-K(+)-ATPase activity in heart and aorta of female Sprague-Dawley
      rats treated with oral contraceptive (OC) steroids. Rats were grouped as control
      (CR), OC-treated and OC+calcium-treated. OC-treated and OC+calcium-treated
      received a combination of OC steriods (ethinyloestradiol and norgestrel; ig).
      OC+calcium-treated rats were fed with 2.5% calcium diet, while OC-treated and CR
      groups were fed on 0.9% calcium diet. The activity of Na(+)-K(+)-ATPase in heart
      and aorta was significantly lower in OC-treated rats than those in the other
      groups. OC treatment caused significant increase in plasma glucose and
      significant decrease in plasma K+ as compared to control group. Decrease in Na(+)
      K(+)-ATPase activity and plasma K+ was abrogated by increased calcium intake,
      while increase in plasma glucose was not normalized by calcium supplementation.
      Plasma levels of Na+, lipid peroxidation index and ascorbic acid were comparable
      among the three groups. These results showed that OC treatment could lead to
      impaired activity of cardiac and vascular Na(+)-K(+)-ATPase, possibly due to
      reduced plasma K+ level and these effects could be abolished by high calcium
      diet.

PMID- 17205707
TI  - Effect of ovine follicular fluid peptide on ovarian responses and other organ
      weights in rats, Rattus norvegicus Berkenhout 1769.
AB  - The present study was aimed to study the effect of an ovine follicular fluid
      peptide on ovarian follicle and good oocyte numbers and weights of ovary, uterus,
      liver, pancreas and kidney in rats, R. norvegicus. A 30.1 kDa peptide was
      isolated from ovine follicular fluid by ammonium sulphate precipitation and then
      gel filtration. The peptide was tested at various levels in normal (22 and 36 day
      old), superovulated (29 day-old) immature and 121-day old mature rats on the
      ovarian responses and other organ weights. The isolated peptide inhibited the
      growth of antral follicles in normal and superovulated rats. Ovarian, uterine
      weight and recovery of good oocytes were reduced when the peptide was
      administered at 100 microg dose. The peptide had no effect on kidney, liver,
      pancreas weight and recovery of preantral follicles.

PMID- 17205708
TI  - PAF antagonism modifies neuroprotective action of histone deacetylase and
      calcineurin phosphatase inhibitors in mice.
AB  - To evaluate the hypothesis that platelet activating factor (PAF) antagonism may
      affect the functional recovery following the nerve injuries and also to evaluate
      the effect of PAF receptor antagonism on the neuroprotective effect of tacrolimus
      and sodium valproate, effect of PAF receptor antagonist, WEB2086 was evaluated in
      animal models of sciatic nerve crush and endothelin-1 induced focal cerebral
      ischemia. WEB2086, per se, while attenuating spontaneous sensory motor recovery
      after sciatic nerve crush, enhanced functional recovery after focal cerebral
      ischemia. WEB2086 also attenuated the neuroprotective effect of tacrolimus and
      sodium valproate subsequent to peripheral nerve injury, while it significantly
      improved the neuroprotective action of tacrolimus and sodium valproate following
      cerebral ischemia reperfusion injury. These results suggest that PAF receptor
      antagonists alone and in combination with tacrolimus/sodium valproate could be
      used in the treatment of cerebral ischemia reperfusion injuries however, their
      use following peripheral nerve injuries could be detrimental.

PMID- 17205709
TI  - Ethanolic Zingiber officinale R. extract pretreatment alleviates isoproterenol
      induced oxidative myocardial necrosis in rats.
AB  - Ethanolic Z. officinale (ZO) extract (200 mg/kg) pretreatment for 20 days in
      isoproterenol (ISO)-treated rats significantly increased the levels of endogenous
      myocardial antioxidants (catalase, superoxide dismutase and tissue glutathione),
      decreased the levels of serum marker enzymes (lactate dehydrogenase, creatine
      kinase, aspartate transaminase and alanine transaminase) and increased myocardial
      lipid peroxides. Histological examination of rat's heart section confirmed
      myocardial injury with ISO administration and near normal pattern with ethanolic
      ZO extract pretreatment. The results of the present study, for the first time,
      provide clear evidence that the ethanolic ZO extract pretreatment enhances the
      antioxidant defense against ISO-induced oxidative myocardial injury in rats and
      exhibit cardioprotective property.

PMID- 17205710
TI  - Evaluation of aqueous leaves extract of Moringa oleifera Linn for wound healing
      in albino rats.
AB  - Aqueous extract of leaves of M. oleifera was investigated and rationalised for
      its wound healing activity. The aqueous extract was studied at dose level of 300
      mg/kg body weight using resutured incision; excision and dead space wound models
      in rats. Significant increase in wound closure rate, skin-breaking strength,
      granuloma breaking strength, hydroxyproline content, granuloma dry weight and
      decrease in scar area was observed. The prohealing actions seem to be due to
      increased collagen deposition as well as better alignment and maturation. From
      the results obtained, it may be concluded that the aqueous extract of M. oleifera
      has significant wound healing property.

PMID- 17205712
TI  - Hypolipidemic and antihyperlipidemic effects of Lagenaria siceraria (Mol.) fruit
      extracts.
AB  - Bottle gourd [(Lagenaria siceraria (Mol.) Stand.] fruit is ascribed with many
      therapeutic effects. The present study was undertaken to explore the
      antihyperlipidemic effect of four different extracts viz. petroleum ether,
      chloroform, alcoholic and aqueous extracts from bottle gourd in Triton-induced
      hyperlipidemic rats and their hypolipidemic effects in normocholesteremic rats.
      The study is comprised preliminary phytochemical screening of the extracts. Oral
      administration of the extracts, at doses of 200 and 400 mg/kg body weight in
      rats, dose-dependently inhibited the total cholesterol, triglycerides, low
      density lipoproteins level, and significantly increased the high density
      lipoproteins level. However, petroleum ether extract did not show the significant
      effects. Both the chloroform and alcoholic extract exhibited more significant
      effects in lowering total cholesterol, triglycerides and low density lipoproteins
      along with increase in HDL as compared to the others. Preliminary phytochemical
      screening revealed the presence of flavonoids, sterols, cucurbitacin saponins,
      polyphenolics, proteins, and carbohydrates. The results obtained suggest marked
      antihyperlipidemic and hypolipidemic activity of the extracts.

PMID- 17205711
TI  - Enhanced wound contraction and epithelization period in steroid treated rats:
      role of pyramid environment.
AB  - Contribution and role of a pyramid/square box on the wound healing suppressant
      effect of dexamethasone was studied in rats of either sex using excision wound
      model to record the wound contraction rate and epithelization period. The results
      showed enhanced wound contraction rate and decreased epithelization period in the
      pyramid-exposed rats as compared to controls. Thus, it appears that pyramid
      environment facilitates the process of wound healing. Also, the wound healing
      suppressant effects of dexamethasone were significantly reduced.

PMID- 17205713
TI  - Potentiation of pentobarbital hypnosis by Rosa damascena in mice.
AB  - Rosa damascena has been found to act on central nervous system including brain.
      It inhibits the reactivity of the hypothalamous and pituitary systems in rat. In
      traditional medicine hypnotic effect of Rose is also suggested. In the present
      study hypnotic effect of ethanolic, aqueous and chloroformic extracts of R.
      damascena was investigated in mice. Hypnotic method was based on potentiation of
      pentobarbital induced sleeping time by extracts. Three doses of extracts (100,
      500 and 1000 mg/kg) were injected i.p. in comparison with diazepam (3mg/kg) as
      positive control and saline as negative control. After 30 min of injection of
      extracts, pentobarbital (30mg/kg) was injected and increase in sleeping time by
      extracts was recorded. The results showed that the ethanolic and aqueous extracts
      in 500 and 1000 mg/kg doses significantly increased pentobarbital induced
      sleeping time which was comparable to diazepam. The chloroformic extract had no
      hypnotic effect.

PMID- 17205714
TI  - Green tea [Camellia sinensis (L.) O. Kuntze] extract reverses the despair
      behaviour in reserpinised and diabetic mice.
AB  - Green tea (C. sinensis) extract (GTE) dose dependently produced reversal of
      despair in normal, reserpinised and diabetic mice, thereby demonstrating an
      antidepressant effect. Although the exact mechanism is yet to be explored, the
      possible inhibition of catechol-o-methyl transferase and monoamine oxidase
      enzymes may be responsible for antidepressant activity of GTE.

PMID- 17205715
TI  - Survival, nodulation and N2 fixation ability of root nodule bacteria under
      different nutritional regimes.
AB  - Eleven strains of Rhizobium and five strains of Bradyrhizobium were examined for
      their viability as well nodulation and nitrogen fixation ability after storage
      under different conditions for two years. The storage conditions comprised
      lateritic soil, lateritic soil plus 1% mannitol, lateritic soil plus 0.1% yeast
      extract, lateritic soil plus 1% mannitol and 0.1% yeast extract, organic soil,
      organic soil plus 1% mannitol, organic soil plus 0.1% yeast extract, organic soil
      plus 1% mannitol and 0.1% yeast extract, and sterile distilled water. All the
      slow growing strains showed better viability than the fast growing strains in any
      of these conditions. The survived strains maintained their nodulation ability
      about 50-60% after one year and 40-50% after two years of preservation as
      compared to control, but the nodulation ability in sterile distilled water was
      very poor. Acetylene reduction activity in the nodules was found to be 70-90% and
      50-70% after 12 and 24 months of preservation, respectively. The strains retained
      their phenotypic characters like antibiotic resistance and salt tolerance up to
      their highest survivability in respective nutritional condition.

PMID- 17205716
TI  - Morphological variation, histology, histochemistry and nutrient contents of
      Frankia root nodules in Casuarina equisetifolia.
AB  - Root nodules were collected from the existing plantation of Casuarina
      equisetifolia from three different agroclimatic zones of Tamil Nadu, India.
      Morphological variation, histology, histochemistry and nutrient contents of the
      nodules were studied. The nodules were found to be simple, dichotomously branched
      and coralloid. The stele in simple and branched nodules reached up to the tip of
      the nodules. Structure of Frankia nodules was described using histochemical
      methods to elucidate the nature of micro-symbiont within the nodules. The nodule
      consisted of a distinct periderm enclosing the cortex. The cortex showed patches
      of infected cells interspersed among the uninfected ones. Inside the cortex was a
      stele bound by an endodermis, which contained high amount of tannin. The micro
      symbiont was observed in the nodule tisues in hyphal form and spore packed
      sporocorp was also seen in the cortex. The histochemical tests revealed the
      presence of proteins, insoluble polysaccharides and polyphenols.

PMID- 17205717
TI  - Mutation in mexR-gene leading to drug resistance in corneal keratitis in human.
AB  - The present study deals with the genetic polymorphism of the mexR gene which is
      involved in the resistance to drugs like ciprofloxacin. Mutations in mexR result
      in increased resistance to multiple antibiotics due to overexpression of this
      efflux system. The MexR product contains 147 amino acids with a molecular mass of
      16,964 Da. We detected 28 point mutations in 14 samples from corneal scraping
      infected with Pseudomonas aeruginosa, which were screened for ciprofloxacin
      resistance. Twenty four were silent mutations and four missense mutations.
      Mapping these mutations was done by using in silico methods on the protein 3D-
      structure obtained from PDB database, localized at 3 specific sites. Single amino
      acid changes (mutations) may influence MexR stability or its ability to dimerise,
      and thus result in the conformation changes at the DNA-binding domain, of the
      structure. Hence it is concluded that the mutations in the DNA binding domain of
      mexR gene could be one of the factors contributing to the possible drug
      resistance in these patients.

PMID- 17205718
TI  - [Characterization of the organic crystal DAST as a THz emitter].
AB  - Using THz time-domain spectroscopy, the home-grown organic crystal DAST and
      widely used high-efficient ZnTe were characterized as THz emitters. Bolometer was
      also used to measure the absolute energy of THz radiation from DAST and ZnTe. The
      refractive index and absorption coefficient of DAST were measured too. It is
      concluded that the home-grown DAST is a kind of high-efficiency THz material, and
      could become a good THz emitter and detector after the improvement in growing
      process.

PMID- 17205719
TI  - [Investigation on spectroscopic properties of Yb3+ -doped laser glasses].
AB  - Yb3+ -doped borosilicate glasses were prepared at high tempreture. The absorption
      spectra and fluorescence spectra were measured at room temperature. The
      integrated absorption cross section, stimulated emission cross section and
      fluorescent time were calculated. The results showed that the main peak
      wavelength was 975.15 nm in absorption spectra with one subpeak near 937.17 nm;
      emission peak was at 977.15 nm in fluorescence spectra with one subpeak near
      997.42 nm; with increasing the sample thickness from 0.5 to 5 mm, luminescence
      intensity became greater, and the peak shifted to longer wavelength from 995.79
      to 999.02 nm. The effective line width of fluorescence increased from 34.64 to
      54.50 nm; Fluorescence lifetime decreased from 1.04 to 1.00 ms.

PMID- 17205720
TI  - [Spectroscopic diagnostics of DC argon plasma at atmospheric pressure].
AB  - The optical emission spectra of DC argon plasma at atmospheric pressure were
      measured inside and outside the arc chamber. The electron temperature was
      determined from the Boltzmann plot, and the electron density was derived from
      Stark broadening of Ar I lines. The criteria for the existence of local
      thermodynamic equilibrium (LTE)in the plasma was discussed. The results indicate
      that the DC argon plasma at atmospheric pressure under our experimental
      conditions is in LTE.

PMID- 17205721
TI  - [Spectral properties and energy transfer of Ce3+ and Eu2+ ions co-doped Ba2SiO4 :
      xCe3+, 0.02Eu2+ green phosphor for white LEDs].
AB  - In the present paper, Ce3+ and Eu2+ co-doped silicate Ba2SiO4:xCe3+, 0.02Eu2+
      green-emitting phosphors were synthesized by conventional solid-state reaction in
      a CO-reductive atmosphere. The diffuse reflection spectra, excitation spectra,
      and emission spectra of Ba2SiO4 : xCe3+, 0.02Eu2+ were measured and studied. Due
      to the good overlap between the Ce3+ emission bands and the Eu2+ excitation
      bands, the energy transfer between Ce3+ and Eu2+ is expected to be very efficient
      and is confirmed by the emission spectra of Ba2SiO4 : xCe3+, 0.02Eu2+. Co-doped
      Ba2SiO4 : xCe3+, 0.02Eu2+ is efficient green phosphors with the excitation of
      longer wavelength UV light, and the emission intensity is stronger than Eu2+
      doped Ba2SiO4 phosphors. Analyzing the spectra, the authors draw a conclusion
      that the luminescence sensitization of Eu2+ by Ce3+ in Ba2SiO4 : xCe3+, 0.02 Eu2+
      is due to the efficient energy transfer from Ce3+ to Eu2+ under long UV light.

PMID- 17205722
TI  - [Composition and structure evolution of carbon nanotube/silica xerogel composites
      during the process of laser irradiation].
AB  - The composition and structure evolution of carbon nanotube (CNT)/silica xerogel
      composites during the process of laser irradiation was traced by infrared (IR)
      spectra, Raman spectra, transmission electronic microscope (TEM) and pore
      structure analysis. The results of IR and Raman spectra show that during the
      process of laser irradiation the compositions of the composites do not make any
      noteworthy changes, while the matrix silica network becomes perfect and the doped
      CNTs become more graphitized. TEM images and pore structure analysis show that
      the SiO2 granules and the corresponding pore size increase after laser
      irradiation.

PMID- 17205723
TI  - [Bonding structure in silicon nitride thin films containing silicon nano
      particles].
AB  - Non-stoichiometric hydrogenated amorphous silicon nitride (a-SiNx : H) film was
      deposited by helico-wave plasma-enhanced chemical vapour deposition (HWP-CVD)
      technique. The microstructure and bonding characteristics of both as-deposited
      and annealed thin films were studied. Raman scattering measurement shows that
      excess silicon exists in the form of amorphous silicon particles in the as
      deposited sample. The microstructure of crystalline nano-particles silicon
      embedded in silicon nitride matrix in the post-annealed sample was formed.
      Comparing the results of both the Fourier transform infrared spectra and the
      optical absorption spectra of the samples deposited under different conditions,
      it is shown that the microstructure of the thin film depended on the gas flow
      ratio and annealing process. The sample with lower excess silicon shows a lower
      density of defect state at the silicon nanocrystal/SiNx interface due to a higher
      binding hydrogen content. The annealing process induces the decrease in Si-H and
      N--H binding densities. Because of the formation of silicon nanocrystals, the
      annealed samples exhibit a higher structure disorder degree.

PMID- 17205724
TI  - [Synthesis and luminescence of methyl-phenacyl sulfoxide complexes with heavy
      rare earth perchlorate].
AB  - RE(ClO4)3 x L5 x C2H5OH(RE=Gd, Tb, Dy, Tm, Yb; L = C6H5COCH2SOCH3) complexes were
      synthesized. The composion of the complexes was determined by elemental analysis,
      coordination titration, molar conductivities, and TGA studies. The ligand and
      coordination compounds were studied by means of IR spectra, 1H NMR, and the
      Tb(II) coordination compound was studied by means of phosphorescence spectra, and
      fluorescence excitation and emission spectra. Each energy level of Tb3+ was
      calculated according to the fluorescent emission spectra results.

PMID- 17205725
TI  - [Preparation and photoluminescence investigation of erbium-doped zinc oxide
      nanocrystalline].
AB  - Er3+ -doped zinc oxide nanocrystalline powders were successfully prepared by
      chemical precipitation method. Photoluminescence spectrum (PL), photoluminescence
      spectrum excitation(PLE) and X-ray diffraction pattern (XRD) of the
      nanocrystalline ZnO:Er3+ with excitation wavelength 365 nm were measured at room
      temperature. XRD pattern indicates nanocrystalline ZnO:Er3+ has a hexagonal
      wurtzite structure and polycrystallining. The mean grain size of nanocrystalline
      ZnO:Er3+ was calculated with Debye-Scherrer formula. The luminescence process of
      Er3+ -doped zinc oxide nanocrystalline was investigated by using PL and PLE.
      Emissions of S(3/2)(550 nm), 2H(11/2))(521 nm) and 4F(5/2)(456 nm) of Er3+ ions
      were observed in wide visible band of ZnO. By analyzing the spectrum the effect
      of Er3+ -doping on the luminescence of ZnO was studied. An energy transfer from
      excited states of ZnO hosts to doping Er3+ ions centers was disclosed by the fact
      that photoluminescence intensity maximum of nanocrystalline ZnO = Er3+ changed
      with the doping concentration of Er3+.

PMID- 17205726
TI  - [Determination of the error of aerosol extinction coefficient measured by DOAS].
AB  - The method of defining the error of aerosol extinction coefficient measured by
      differential optical absorption spectroscopy (DOAS) is described. Some factors
      which could bring errors to result, such as variation of source, integral time,
      atmospheric turbulence, calibration of system parameter, displacement of system,
      and back scattering of particles, are analyzed. The error of aerosol extinction
      coefficient, 0.03 km(-1), is determined by theoretical analysis and practical
      measurement.

PMID- 17205727
TI  - [Study on intelligent system of hyper-spectral data gathering based on wireless
      data communication technology in farm machinery].
AB  - In order to meet the needs of highly dense and overall farmland information
      gathering, wireless data communicating, and real-time processing in the precision
      agriculture, this system integrated GPS, GIS and RS based on the technology of
      computer and wireless data transmission. On the one hand, the system makes DGPS
      and Hyper-spectrograph integrated through the AT891v52 MCU, providing the
      accurate space position and realizing the integration of spectrum data
      acquisition and orientation. On the other hand, the system realizes the
      communication between the data gathering control system and the microcomputer by
      using the nRF905 system. Meanwhile the system has realized the visualized
      analysis and management of the spectrum data by integrating Visual Basic and Map
      Objects into GIS, displaying real-time trace of moving point and some related
      attributes of the moving point in map layers, and calculating crop derivative
      spectra and crop vegetation index NDVI etc. Thus, sufficient information was
      provided for expert system and decision support system of precision agriculture.

PMID- 17205728
TI  - [Spectroscopy study of molecular recognition of a molecular imprinted
      monocrotophos-specific polymer].
AB  - In the present study, molecular imprinting was used to develop a method based on
      noncovalent interaction for the synthesis of a monocrotophos-specific polymer.
      The selective binding characteristics of the template polymer were evaluated by
      1H NMR and ultraviolet spectrometry. The polymer obtained was found to interact
      specifically with monocrotophos by cooperative hydrogen bonding. The infrared
      spectrometry of the polymer further indicated that there were some functional
      groups in the moleculary imprinted polymer which could interact on the template.

PMID- 17205729
TI  - [Accuracy analysis of pulse oximetry based on dynamic spectroscopy].
AB  - The pulse oximeter used to measure patients oxygen saturation non-invasively and
      continuously, has numerous applications in clinic care. The pulse oximetry
      measurement combines two basic methods, spectrophotometry and
      photoplethysmography (PPG). The red light and the infrared light are exposed to
      the ear lobe, finger or other tissue with fluctuation of artery blood, and then
      detected. The amplitude ratio of the photoplethysmography waveform of red light
      and infrared light varies with the oxygen saturation of blood. The measuring
      principle of the pulse oximeter is based on traditional test method, its accuracy
      is not gratifying due to various factors influencing the measurement result, such
      as the principle, measuring condition, and individual discrepancy. In the present
      paper a new pulse oximetry based on dynamic spectroscopy is introduced, It can
      promote the accuracy of the pulse oximeter evidently. The dynamic spectroscopy
      method is able to eliminate the interference of individual discrepancy and
      measuring condition in principle. This new method can eliminate the measurement
      error of pulse oximetry theoretically.

PMID- 17205730
TI  - [FTIR analysis of the enzymatic degradation of chitosan blend membranes].
AB  - Chitosan blend membranes were prepared by casting the mixture solution of highly
      deacetylated chitosan (HDC) and moderately deacetylated chitosan (MDC). FTIR was
      used to investigate the components of the blend membranes before and after
      lysozymic degradation. It was found that the ratio of MDC in the blen d membranes
      had a linear relation with the degree of deacetylation (DD) of the membranes. In
      enzymatic degradation process, DD of the membranes exhibited an increasing
      tendency. The FTIR data indicate that MDC component in the blend membranes can be
      removed by selective enzymatic degradation. This also suggests that FTIR can be
      used as an efficient and rapid method to investigate the degradation process of
      chitosan.

PMID- 17205731
TI  - [EQCM and in situ FTIR studies on the adsorption and oxidation of 1-butanol at a
      platinum electrode in alkaline media].
AB  - The adsorption and oxidation of 1-butanol in alkaline media on a platinum
      electrode were investigated mainly by EQCM and in situ FTIR spectroscopy. The
      experimental results demonstrate that the electrooxidation of 1-butanol is
      closely relative to solution acidity. Since no chemically adsorbed species, such
      as CO, were evidenced by in situ FTIR spectroscopy, the adsorption of 1-butanol
      or its dissociative products on Pt surface is suggested by EQCM and CV data. Only
      one current peak of 1-butanol oxidation in PGPS was detected at -0.23 V/SCE,
      which illustrated the disappearance of the second current peak due to Pt
      electrode passivation in alkaline media. The final product of 1-butanol oxidation
      is only butyric acid anion under experimental condition. It may therefore be
      suggested that the main reaction occurring at the electrode is the oxidation of 1
      butanol to butyric acid anion. The EQCM studies provide quantitative results of
      surface mass variation and have shed light on elucidating 1-butanol oxidation.

PMID- 17205732
TI  - [Fourier transform infrared spectroscopy study on normal and malignant tissues of
      cervix].
AB  - Fourier transform infrared spectroscopy (FTIR) was used to investigate 35
      cervical tissues , including 17 squamous cell carcinoma of cervical samples, and
      5 adenocarcinoma of cervical samples, 13 normal cervical samples. The results
      show that there are 18 spectral bands with highly appearance percentage(>80%) in
      these three types of tissues, and these spectral bands may be the characteristic
      infrared spectra bands for cervical tissues; Some of relative absorbance ratios
      are statistically significant (p < 0.05) among these three types of tissues.
      These differences of relative absorbance ratios are mainly centered at 1080,
      1238, 1314, 1339, 1397, 1454, 1541, 1647, 2854, 2873, 2926, and 2958 cm(-1). The
      present results indicate that FTIR can be used to distinguish these three types
      of tissues. The utilization of FTIR spectra in cervical tissues is expected to be
      a hopeful method in cervical cancer screening and clinical diagnosis in the
      future.

PMID- 17205733
TI  - [Analysis of several methods for wavelet denoising used in near infrared spectrum
      pretreatment].
AB  - Based on the wavelet analysis, the noise of the near infrared first derivative
      spectrum of rapeseed oil is eliminated. Several popular wavelet denoising methods
      are introduced, including wavelet decomposition and reconstruction method,
      nonlinear wavelet soft-threshold denoising method, and wavelet transform modulus
      maxima method, The results show that the wavelet transform modulus maxima method
      is the best, the nonlinear wavelet soft-threshold method is the second, and other
      are worse. The wavelet transform modulus maxima method can produce more precise
      model with little deviation.

PMID- 17205734
TI  - [Determination of the artificial bezoar powder in bezoar powder by near-infrared
      spectrometry and support vector machine].
AB  - A method for determining the artificial bezoar powder in bezoar powder using near
      infrared (NIR) diffuse reflectance spectrometry was proposed in the present
      paper. The method was based on support vector machine (SVM). The calibration set
      was set up by adding unequal artificial bezoar powder to the bezoar powder
      (content range: 0%-100% ) and collecting the NIR spectrum of the samples in the
      wave number range of 4000-10000 cm(-1). The processing algorithm was wavelet
      transform with first and second derivatives. A mathematical model with support
      vector machine was established. The model was checked with leave one method. The
      sum of the square of the relative prediction error was 0.00135. This method is
      reliable and can be used to control the quality of bezoar powder.

PMID- 17205735
TI  - [A review on applications of infrared spectroscopy to the study of traditional
      Chinese medicine].
AB  - Infrared spectroscopy is well suited for the rapid and nondestructive
      identification and quantification of traditional Chinese medicine (TCM) for its
      high resolution, easy operation and strong specialization of absorbance bands. It
      is becoming an efficient methodology in the quality control of TCM. The present
      paper reviews the applications of infrared spectrometry in the qualitative and
      quantitative analysis of TCM, especially to the discrimination and effective
      content determination of traditional Chinese medicinal materials (including
      different parts of the same medicinal material, TCM from different geographical
      areas, easily confusing TCM, and true and false TCM) and Chinese patent medicine
      (such as TCM formula particles, injections, etc.). With the ceaseless rapid
      development and popularization of FTIR spectrometer and computer science,
      infrared spectrometry will greatly accelerate the process of TCM modernization
      and internationalization by all means.

PMID- 17205736
TI  - [Accurate curve fitting and revising of infrared data based on NUBSC].
AB  - Accurate curve fitting of infrared spectrum data is important for building
      standard spectrum, and is the basic requirement for qualitative and quantitative
      spectral analysis. In the present paper, B-Spline was used to accurately fit the
      infrared spectrum data. Based on the max norm distances of B-Spline curve fitting
      arithmetic, this method not only resolved the curve fitting problem of infrared
      data, but also provided a convenient way to orient peak values of spectrum. The
      authors introduced the B-Spline, realized curve fitting of quadratic non-uniform
      B-Spline curves (for short: NUBSC), and described the precision control of curve
      fitting of infrared spectrum data.

PMID- 17205737
TI  - [Fast algorithm for feature extraction and identification of infrared spectra of
      polluted gases].
AB  - With the multi-resolution analysis, features of infrared spectra of polluted
      gases were extracted. Then the data were trained or identified by a neural
      network system. The experimental results show that the combination of the wavelet
      transform and the neural network has the great ability of feature extracting. And
      the system is quite efficient for identifying infrared spectra.

PMID- 17205738
TI  - [The quality assessment of cigarette paper by SIMCA and PLS combined with near
      infrared spectrum].
AB  - By using algorithm of SIMCA and partial least squares(PLS) combined with Fourier
      transform near infrared spectra (FT-NIR), the classification methods were
      established for the discrimination of cigarette paper. Meanwhile, the calibration
      models were established for the determination of the grammage, thickness,
      permeability, moisture and ash of cigarette paper. Correlation coefficients of
      the models were 0.9768, 0.9664, 0.9470, 0.956 3 and 0.9759, and the root mean
      square errors of cross validation (RMSECV) were 0.5614, 0.0960, 1.2741, 0.0967
      and 0.2603 respectively. The methods has been applied to the determination and
      discrimination of unknown samples with satisfactory results.

PMID- 17205739
TI  - [Advanced development of remote sensing FTIR in air environment monitoring].
AB  - Remote sensing FTIR(RS-FTIR) is one of the most important technologies in
      atmospheric pollutant monitoring. It has several prevailing advantages: (1) high
      resolution and high selectivity; (2) it requiring no sampling and no sample
      preprocessing; (3) capability of detecting several compounds simultaneously; (4)
      real time, long distance, and automatic monitoring. So it is extraordinarily
      appropriate for the quantitative and qualitative determination, and remote, real
      time, dynamic monitoring of air contaminant, especially the toxic volatile
      organic compounds (VOCs). The present paper reviews the research progress in
      remote sensing FTIR for air monitoring made by the Laboratory of Advanced
      Spectroscopy in recent years, including chemometrics, computed tomography, FTIR
      spectra interpretation, spatial distribution of air pollutant concentration and
      passive remote monitoring, etc. These research findings show that the rapid
      development and application of remote sensing FTIR accelerated the temporal and
      spatial extension of analytical chemistry, and it will by all means have wide
      prospects in atmospheric environmental monitoring.

PMID- 17205740
TI  - [FT-Raman spectroscopic investigation on hypothyroid cancer].
AB  - The normal and malignant tissues from hypothyroid were investigated by FT-Raman
      spectroscopy. The results show that two characteristic Raman spectral peaks of
      normal tissues appeared at 503 and 758 cm(-1) (corresponding to theextension
      vibration of C--I band and the vibration of benzene rings respectively) in the
      range of 400-3500 cm(-1). The two peaks disappeared at malignant tissues. The
      intensity of the characteristic vibration peaks of normal tissues appearing at 3
      062 and 1 003 cm(-1) corresponding to tyrosine weakened in malignant tissues.
      Thus, FT-Raman spectroscopy is a potential method in the diagnosis of hypothyroid
      cancer.

PMID- 17205741
TI  - [Raman active vibrations of aluminosilicates].
AB  - Raman spectra of aluminosilicate minerals, namely kyanite, andalusite, and
      sillimanite and K2O-Al2O3-SiO2 glasses were recorded. Four alumino-silicon
      tetrahedral model clusters were calculated by self-consistent (SCF) molecular
      orbital ab-ini-tio calculation of the quantum chem (QC) method. The result shows
      a decrease tendency in Raman frequencies in the 800-1200 cm(-1) frequency region
      with increase in four-coordinated Al content, which is assigned to the Si--Onb
      symmetry stretching vibrations. The Raman spectra in the 700-800 cm(-1) frequency
      region is attributed to Al-Onb symmetry stretching vibrations.

PMID- 17205742
TI  - [Study of the interaction between methotrexate and bovine serum albumin by
      spectrometry].
AB  - The interaction of methotrexate (MTX) and bovine serum albumin (BSA) was studied
      by fluorescence and absorption spectra. The results show that methotrexate
      strongly quenched the fluorescence of bovine serum albumin, and the quenching
      mechanism is a static quenching procedure. The binding constants and the number
      of binding sites between MTX and BSA at different temperatures were calculated.
      Furthermore, the enthalpy and entropy changes in the interaction were also
      obtained, and the primary binding pattern between MTX and BSA was interpreted as
      hydrophobic interaction.

PMID- 17205743
TI  - [Spectra and structural analysis of high boiling solvent lignin from Bagasse].
AB  - Bagasse high boiling solvent lignin is a polymer prepared by high boiling solvent
      pulping process. In the IR spectra, the absorbance of HBS lignin at 1700 and 1
      328 cm(-1) is present. It is showed that the nonconjugated carbonyl existed. The
      strong absorbance of UV spectra of HBS lignin is about 201 nm for n-->pi electron
      transition, which indicates that the HBS lignin is an unsaturated polymer. Judged
      from the 1H NMR, the syringyl and guaiacyl group in the lignin is present. The
      element composition and the content of OCH3 group were investigated. The
      empirical C9-formula of the lignin is C9H9.79O2.58(OCH)0.75 according to dealing
      with the experiment data. The weight-average molecular weight of the HBS lignin
      is 2674 g x mol(-1).

PMID- 17205744
TI  - [Preparation and spectral analysis of a new type of blue light-emitting material
      delta-Alq3].
AB  - In the present article, delta-Alq3, a new type of blue light-emitting material,
      was synthesized and investigated by IR spectra, XRD spectra, UV-Vis absorption
      spectra, photoluminescence (PL) spectra, and electroluminescence (EL) spectra.
      The relationship between molecular spatial structure and spectral characteristics
      was studied by the spectral analysis of delta-Alq3 and alpha-Alq3. Results show
      that a new phase of Alq3 (delta-Alq3) can be obtained by vacuum heating alpha
      Alq3, and the molecular spatial structure of alpha-Alq3 changes during the vacuum
      heating. The molecular spatial structure of delta-Alq3 lacks symmetry compared to
      alpha-Alq3. This transformation can reduce the electron cloud density on
      phenoxide of Alq3 and weaken the intermolecular conjugated interaction between
      adjacent Alq3 molecules. Hence, the pi--pi* electron transition absorption peak
      of delta-Alq3 shifts toward short wavelength in UV-Vis absorption spectra, and
      the maximum emission peak of delta-Alq3 (lamda max = 480 nm) blue-shifts by 35 nm
      compared with that of alpha-Alq3 (lamda max = 515 nm) in PL spectra. The maximum
      emission peaks of delta-Alq3 and alpha-Alq3 are all at 520 nm in EL spectra.

PMID- 17205745
TI  - [A new spectral method for the determination of cationic surfactant based on the
      resonance scattering effect of AgI2- association particles].
AB  - In pH 3.5 NaAc-HCl medium, there is a maximum resonance scattering (RS) peak at
      360 nm and a synchronous scattering peak at 470 nm for the association particle
      system of (CTMAB-AgI2)n in white color, with a diameter of 700 nm. The CTMAB
      concentration cCTMAB in the range of 2.0-50.0 x 10(-7) 4 mol x L(-1) is linear to
      the I360 nm value. Its regression equation is I360 nm = 2.03 x 10(7) cCTMB +
      0.48, and regression coefficient is 0.9985. The detection limit is 8.0 x 10(-8)
      mol x L(-1). A new RS method has been proposed for the determination of cationic
      surfactant in samples with satisfactory results. The laser scattering and RS
      spectra show that CTMAB+ and AgI2- combine to CTMA-AgI2- association molecule by
      means of attractive forces. The association molecules automatically aggregate to
      (CTMA-AgI2)n association particles, so that the particles exhibit a resonance
      scattering peak at 360 nm, and the system is in white color.

PMID- 17205746
TI  - [Spectroscopic studies on the binding of prulifloxacin and ct-DNA].
AB  - The interaction mechanism of prulifloxacin (PL) and calf thymus DNA (ct-DNA) was
      studied by UV spectra, fluorescence spectra, and hydrodynamic measurements. The
      binding of ct-DNA and different concentrations of PL was discussed with UV, FL,
      phosphate effect and ion strength. The denaturation temperature and viscosity
      were measured. It is obvious that there is a hypochromic effect on the UV spectra
      with the fluorescence intensity decreasing regularly after addition of DNA and a
      red shift of the maximum emission peak with a static quenching constant of 3.1 x
      10(4) L x mol(-1). The above results show that a binary complex forms between PL
      and DNA. It is indicated that there is no static-electro interaction between them
      by phosphate effect. The outer groove binding is suggested by denaturation
      temperature of DNA increasing (no more than 7 degrees C) and viscosity slightly
      decreasing.

PMID- 17205747
TI  - [Studies on the interaction between thionine and deoxyribo-nucleic acid by
      ethidium bromide probe].
AB  - The interaction between thionine and deoxyribonucleic acid was studied with
      ethidium bromide probe in Tris-HCl buffer solution at pH 7.4 by fluorescence
      spectra, electronic absorption spectra, and resonance light scattering spectra.
      From the obtained results, it was found obviously that the planar structure of
      thionine can be intercalated into the stacked base pairs of DNA, which is the
      major controlling factor. The binding constant was found to be 1.0 x 10(5) L x
      mol(-1).

PMID- 17205748
TI  - [Study on the mechanism of interaction between TH-PF-Mo(VI) complex and bovine
      serum albumin by fluorimetric method].
AB  - The mechanism of interaction between bovine serum albumin (BSA) and
      trihydroxylphenylfluorone (TH-PF)-Mo(VI) complex in neutral solution was studied
      by fluorimetric method. The mechanism of fluorescence quenching of BSA caused by
      (TH-PF)-Mo(VI) complex probe was investigated and the binding constants under
      different temperature were measured. The binding constants of the reaction at 25
      degrees C and 40 degrees C were calculated by fluorimetric method to be 4.78 x
      10(4) L x mol(-1) and 3.72 x 10(4) L x mol(-1), respectively. According to the
      theory of Forster non-radiation energy transfer, the binding distance and
      transfer efficiency at 25 degrees C were calculated to be 2.89 nm and 0.314,
      respectively. Furthermore, the thermodynamic parameters were measured and the
      results indicated that electrostatic force played a major role in the interaction
      between TH-PF-Mo(VI) complex and BSA.

PMID- 17205749
TI  - [Extraction and analysis of gracilaria gigas Harvey polysaccharides].
AB  - Gracilaria Gigas Harvey Polysaccharides (GHPS) were extracted with hot water and
      sedimentated with ethanol. The amount of polysaccharides was determined by phenol
      H2SO4 method. The mineral elements and molecular configuration were analysed by
      inductively coupled plasma (ICP) and infrared absorption spectrum (IR). The rate
      of distillation was 14.98%, the amount of polysaccharides was 78.2%, and GHPS
      contained manifold mineral elements (Ca, Fe, Mg and S). The IR spectra manifested
      that the extraction was a compound of polysaccharides, i.e. acidic
      polysaccharides.

PMID- 17205751
TI  - [Pretreatment of supported Wacker catalysts and the determination of palladium
      and copper].
AB  - The supported Wacker catalysts were pretreated with two different methods. Then
      copper and palladium were determined by inductively coupled plasma atomic
      emission spectrometry(ICP-AES). The results showed that the best pretreatment
      method is burning-acid dissolving. With this method, the detection limits of Pd
      and Cu were 3.127 and 2.548 ng x mL(-1), the recoveries of standard addition of
      Pd and Cu were 96.26% and 94.82%, and the relative standard deviations (n=11) of
      Pd and Cu were less than 1.237% and 1.354%, respectively. The method is
      efficient, accurate, and easy to operate. Pd and Cu in supported Wacker
      catalysts, which were sampled before calcination, after calcination and after
      reaction, were determined by this method, and the contents were compared with
      calculated values. The percentages were larger than 96.4% and 96.6% respectively.
      It is considered that the active components did not decrease in preparation and
      reaction.

PMID- 17205750
TI  - [Studies on the contents of twenty elements in different parts of garlic by using
      ICP-OES, AAS and AFS combined with microwave decomposition method].
AB  - The garlic plants sampled in the suburbs of Suzhou were rinsed thoroughly with
      deionized water, and divided into six different parts: root, low stem, middle
      stem, high stem, tender leaves and old leaves. After decomposition in a microwave
      oven, the contents of Al, As, B, Ca, Cd, Cr, Cu, Fe, Hg, K, Mg, Mn, Na, Ni, P,
      Pb, S, Se, Sr and Zn in these parts were determined by using ICP-OES, AAS and
      AFS, and the contents of these 20 elements in garlic bulbs collected from the
      same location were also determined. It was found that the tender leaves or the
      bulbs of garlic should be chosen preferably for the extraction of active
      compounds, because they are much richer in Cu, Fe, Mn, S, Se and Zn elements and
      rather low in harmful As, Cd, Hg and Pb elements as compared with other parts of
      garlic. The contents of 20 elements are varied in six different parts of garlic,
      from which some useful conclusions can be drawn concerning either physiological
      properties of garlic or situations of atmosphere contamination.

PMID- 17205752
TI  - [Study on NPLS model with three-dimensional hyperspectrum for assessing per-mu
      yield of winter wheat].
AB  - The present study piled a cube array with the winter wheat's cap reflection
      hyperspectra sampled from 35 experimental districts during 8 growth periods, and
      then used a multiway partial least squares (NPLS) algorithm to establish a model
      to assess the per-mu-yield of winter wheat. The model was used to predict the per
      mu-yields of other 13 experimental districts. The correlation coefficient of
      predicted and actual values was 0.9366, and the mean relative error was 4.44%.
      These results showed a good prediction of the model. The study has guiding
      meaning to actual yield assessment.

PMID- 17205753
TI  - [Analyzing the effect of field frequencies on reconstructive accuracy of rebuilt
      field with spectroscopy].
AB  - The field to be reconstructed was simulated with numerical simulation technique.
      The effect of a three-dimensional field's characteristics, especially, its
      frequency components, on the reconstructive accuracy was discussed with
      spectroscopy. A double-peaked field model was built with Gaussian function, and
      its frequency components were analyzed by Fourier transform. With algebraic
      reconstruction technique, the model field was reconstructed. The reconstructed
      field was analyzed with many error indexes. As a result, the reconstructed field
      was similar to the model one in respect of the position, pointing and shape of
      the peaks, but the heights of the peaks were shorter than those of corresponding
      ones in the model. The border of the reconstructive field showed obvious
      fluctuation. It was considered that the main causation of the reconstructive
      result was the filtering inserted in iterating process. To confirm this idea, the
      convergence factor, represented with A, of Gaussian function was changed from six
      to thirty in order to change the frequency components of the model field, and the
      same numerical simulation as the one for the first model field with A=18 was
      carried out for these new model ones consisting of different frequency. As a
      result, the idea proved to be right. At the same time, it was found that the
      characteristics of the field at the edge of the reconstructed zone had a deeper
      effect on the reconstructive accuracy. When the precondition that the field edge
      approximated to zero could no longer existed, the reconstructive accuracy
      declined, and furthermore, it would make iterating process divergent. From all
      the above, the characteristics of the field at the edge should draw much
      attention when we reconstruct a field with Algebraic reconstruction technique.

PMID- 17205754
TI  - [Wavelength interval selection by iteratively reinitialized GA and its
      application to spectrophotometric determination of components in cough syrup].
AB  - Wavelength selection in PLS calibration can be used to reach two goals: improve
      the predictive ability and simplify the model. Iteratively reinitialized GA is a
      modified genetic algorithm, and it gives an initializing procedure of selecting
      the first candidates for every run of GA, which uses the results of previous runs
      as the guiding information. This algorithm can select wavelength regions instead
      of scattering points, which is very helpful in understanding the relevant parts
      of spectra. Furthermore, the continuous wavelength points make the PLS model more
      robust. Appling IRGA based wavelength selection to the UV-Vis spectrum of cough
      syrup, the result illustrates that PLS regression can greatly benefit from
      variable selection when used for multicomponent spectrophotometric determination.

PMID- 17205755
TI  - [Slurry sampling for direct determination of trace cadmium in amber by graphite
      furnace atomic absorption spectrometry].
AB  - A method for the direct determination of trace cadmium in amber by graphite
      furnace atomic absorption spectrometry (GFAAS) with slurry sampling was
      described. Palladium nitrate was used as a matrix modifier to eliminate the
      interference. Slurry stability and the influences of the matrix modifier,
      ashing/atomization temperature and coexistent ions on analytical signals were
      investigated in detail. Under the optimized experimental conditions, the
      detection limit of this method was 9.4 ng x g(-1) with a precision of 6.1%.

PMID- 17205756
TI  - [Determination of eleven trace elements in Chinese traditional and herbal drugs
      for relieving heat and toxic by FAAS].
AB  - Chinese traditional herbal drugs for relieving away heat and toxic were treated
      with cineration, and the residues were dissolved by HNO3. Eleven trace elements
      including, calcium, magnesium, manganese, copper, iron, zinc, cadmium, lead,
      cobalt, nickel and chromium in twenty sample solutions were determined by flame
      atomic absorption spectrometry. The results obtained show that the contents of
      calcium, magnesium, iron, zinc, manganese and copper are abundant, and the
      addition standard recoveries (n=5) were 90%-110%.

PMID- 17205757
TI  - [Determination of thirteen metal elements in the plant Foeniculum vulgare Mill.
      by flame atomic absorption spectrophotometry].
AB  - The objective of the paper is to determine the amount of metal elements of Na, K,
      Mg, Ca, Cu, Zn, Mn, Fe, Co, Ni, Cd, Cr and Pb in the planted Foeniculum vulgare
      Mill. by flame atomic absorption spectrophotometry (FAAS), after the cinefaction
      and the digestion with HNO3-HClO4 (phi 4:1) at 90-95 degrees C and normal
      pressure. The optimum parameters of FAAS and the effects of solution medium on
      the results were investigated. The analytical results show that the amount of Na,
      K, Mg, Ca, Mn, Fe, Cu, Zn and Pb was 1508.7, 27653.0, 2036.0, 4848.1, 24.8,
      323.5, 15.2, 23.7 and 10.8 microg x g(-1), respectively, and that of Co, Ni, Cd
      and Cr was not checked out in the samples. The recovery of standard addition is
      97.45%-102.50%, the relative standard deviation (n=9) was 0.34%-2.77%. The
      characteristic method is quick, simple and convenient and the results are
      satisfactory.

PMID- 17205758
TI  - [Synthesis, characterization and photo degradation application for dye-rhodamine
      B of nano-iron oxide/bentonite].
AB  - The iron oxide/bentonite was prepared through a reaction of a solution of OH-Fe
      salt with bentonite clay dispersion. BET, XRD an d HRTEM were used t o study i ts
      surface area, microstructure, and average particle size. The iron oxide/bentonite
      nano composite was developed as the heterogeneous catalyst for successful
      discoloration and mineralization of dye rhodamine B And the effects of solution
      pH, H2O2 molar concentration, catalyst loading and initial rhodamine B
      concentration were studied in detail by photometric method. The process of
      degradation was traced by UV-Visible spectrum. Besides, the comparison between
      the heterogeneous photo-Fenton process and homogeneous photo-Fenton process was
      performed. The result shows that, it has large surface area and mainly consists
      of high catalytic activity alpha-Fe2O3. The discoloration ratio is up to 97% and
      the COD(Cr), removal ratio is 71% after 4 h in the presence of pH 3.0, 2.5 x 10(
      5) mol x L(-1) rhodamine B 100 mL, 0.3 g x L(-1) catalyst, 10 mmol x L(-1) H2O2
      and UV. The rhodamine B degradating speed of heterogeneous photo-Fenton process
      is much faster than that of homogeneous photo-Fenton process. The catalyst can be
      reused after being treated.

PMID- 17205759
TI  - [Spectral studies of novel Na specific adsorbent Li(1+x)Al(x)Ti(2-x)(PO4)3].
AB  - A novel Na specific adsorbent Li(1+x)Al(x)Ti(2-x)(PO4)3 was synthesized by high
      temperature solid state reaction method. The samples were characterized by X-ray
      diffraction(XRD) and scanning electron microscope(SEM). Raman and FTIR
      spectroscopic studies of these materials were carried out, and the vibrational
      bands were assigned. Their adsorption performances were investigated. The results
      indicate that the low concentration (x < 0.6) Al dopant does not affect the
      structure of the material but makes it able to selectively adsorb sodium. The
      adsorbing test results show that its exchange capacity is high with the maximum
      value of adsorption capacity of 11.76 mg x g(-1) at x = 0.4 and pH = 10.0-11.0.
      So it can be used to remove the microamounts impurity-sodium in the production of
      high purity lithium salt.

PMID- 17205760
TI  - [Theoretical analysis of the spectral line missing stage in crystal X-ray
      diffraction based on the diffraction of grating].
AB  - In the present paper, the theoretical analysis was performed of the phenomenon
      and causes of the spectral line missing stage in diffraction of grating and
      crystal X-ray diffraction, and their application was discussed. It was concluded
      that the crystal X-ray diffraction probably lies in the fact that the geometrical
      structure factor of unit cells of some crystal materials is zero, and secondly,
      the spectral line missing stage in diffraction could be an interesting subject in
      the crystal X-ray diffraction research. On the whole, these conclusions may
      provide an important reference to the study on material phase, structure and
      intact analysis etc.

PMID- 17205761
TI  - [Optical-fiber Fourier transform spectrometer].
AB  - A novel Fourier transform spectrum analyzer based on a single mode fiber Mach
      Zehnder interferometer is reported. An optical fiber Fourier transform
      spectrometer, with bulk optics components replaced by fiber optical components
      and with the moving mirror replaced by a piezoelectric element fiber stretcher
      was constructed. The output spectrum of a LD below threshold was measured.
      Experiment result agrees with that by using grating spectrum analyzer, showing
      the feasibility of the optic fiber Fourier transform spectrometer for practical
      spectrum measurement. Spectrum resolution -7 cm(-1) was obtained in our
      experiment. The resolution can be further improved by increasing the maximum
      optical path difference.

PMID- 17205762
TI  - [The project and simulation of a compositive miniature spectrum instrument based
      on the array of Fabry-Perot cavity].
AB  - This paper advances a kind of micro-spectrometer based on Fabry-Perot cavity's
      character of filtering the waves. The basic structure of the micro-spectrometer
      is the array of Fabry-Perot cavity which contains many different lengths of
      cavity on the substrate of silicon, consequently the authors can achieve the
      detection at several wavelengths simultaneously. The unit of probing is a Fabry
      Perot cavity made up of the substrate of silicon-metal film-silicon dioxide layer
      metal film. The authors carried out the corresponding simulation. In the basic
      structure of aluminum film(14 nm)-silicon dioxide layer-silver film(39 nm), the
      resolution can reach 15 nm. When the area of a unit of probing is 0.14 mm x 0.14
      mm only, it can reach the luminous flux of miniature grating spectrum instrument
      (the minimum volume in the order of cm), but the volume of the part of spectrum
      detection is only of the order of mm. The design size of the micro-spectrometer
      is a few millimeters. Furthermore it has no movable parts and could detect
      several wavelengths at the same time. It is possible to fabricate such micro
      spectrometer through existing processing methods of IC technology.

PMID- 17205763
TI  - [Spectra classification based on generalized discriminant analysis].
AB  - A kernel based generalized discriminant analysis (GDA) technique is proposed for
      the classification of stars, galaxies, and quasars. GDA combines the LDA
      algorithm with kernel trick, and samples are projected by nonlinear mapping onto
      the feature space F with high dimensions, and then LDA is conducted in F. Also,
      it could be inferred that GDA which combines the extension of Fisher's criterion
      with kernel trick is complementary to kernel Fisher discriminant framework. LDA,
      GDA, PCA and KPCA were experimentally compared with these three different kinds
      of spectra. Among these four techniques, GDA obtains the best result, followed by
      LDA, and PCA is the worst. Although KPCA is also a kernel based technique, its
      performance is not satisfactory if the selected number of the principal
      components is small, and in some cases, it appears even worse than LDA, a non
      kernel based technique.

PMID- 17205764
TI  - [The absorption spectrum of green-sensitive cyanine dyes J-aggregate adsorbed on
      silver chloride microcrystals].
AB  - The silver chloride microcrystals emulsion which are sensitized by the adsorbed
      green-sensitive cyanine dye of different concentration, was studied by using the
      absorption spectrum. The experiments show that when the sensitizing concentration
      is less than 0.02 mL (5.0 mg x mL(-1))/40 g emulsion, the dye J-aggregate is not
      formed on the surface of silver chloride microcrystals; when the dye
      concentration is more than 0.2 mL (5.0 mg x mL(-1)/40 g emulsion, the dye J
      aggregate is formed on the surface of silver chloride microcrystals; compare to
      the M-state of dye, the maximal absorption peak of J-aggregate shifted to a
      longer wavelength by about 50 nm. It was found, when the J-aggregate is formed,
      the absorption in the wavelength range of more than 450 nm is increased.

PMID- 17205765
TI  - [The influence of gastroesophageal reflux on the course and therapy of bronchial
      asthma].
AB  - The epidemiological and clinical data suggest the influence of gastroesophageal
      reflux disease (GER) on the course of bronchial asthma (BA). Pathogenetic
      relationships of both diseases are still not clear. The most possible theory
      seems to be micro-aspirations of refluxing digestive contents leading to the
      development of bronchial inflammation. It is increasingly improved the benefits
      of treatment for gastroesophageal reflux on asthma course. Apart from advices
      referring proper diet and resting with semirecumbent position, the most effective
      method of treatment seems to be appropriately high dose of proton pump
      inhibitors. It is seamed that in some cases an important role in development of
      GER could play hypotention produced in mediastinum in patients with exacerbated
      course of asthma. It is suggested to connect treatment of both illnesses to
      benefit in clinical course of GER and BA as well.

PMID- 17205766
TI  - [Positive microvolt T-wave alternans as a marker of ventricular arrhythmia
      trigering during cardioverter-defibrillator implantation].
AB  - Microvolt T-wave alternans (MTWA) is promising method for noninvasive assessment
      of arrhythmic risk, but its role hasn't established yet. The aim of this study
      was to establish the MTWA potency to predict the ventricular arrhythmia
      triggering during implantable cordioverter-defibrillator (ICD) implantation.
      Material and metods. The study group consisted of 21 patients, aged 63.0+/-8.0
      years; EF was 38.0+/-12.8%. Seventeen of them had a history of myocardial
      infarction and 4 had non-ischemic cardiomyopathy. The reason for ICD implantation
      were secondary prevention due to nonfatal cardiac arrest caused by VF/VT in
      nineteen patients and in two patients ICD was implanted because of unexplained
      syncope and low EF (< or =35%). All patients underwent VT/VF triggering during
      device implantation caused by electrophysiological study (EPS). If this proved
      ineffective aggressive protocol of 50 Hz BURST and T SHOCK was applied. After ICD
      implantation the following tests were performed: ECG with HR, QRS and QTc
      evaluation, 24-hour ECG Holter monitoring with HRV assessment and MTWA evaluation
      during treadmill exercise test. Results. In the group with VT/VF induced by less
      aggressive protocol (EPS), group I (n = 10) MTWA was present in nine patients, in
      one the result of MTWA was indeterminate. In the group with VT/VF induced by more
      aggressive protocol, group II (n = 11) MTWA was present in four patients,
      indeterminate in four and absent in three. There was a significant (p = 0.017)
      difference between group I and II in the frequency of positive result of MTWA.
      There were no differences between the two groups according to time domain
      parameters of HRV such as SDNN, RMSSD and PNN50 and QTc. There was a significant
      difference between the two groups in time duration of QRS complexes, 118.9+/-14.7
      vs. 105.6+/-11.5 accordingly (p < 0.04). Conclusions. MTWA may help identify
      patients in whom VTNVF is more easily inducible by electrophysiologic study
      during ICD implantation. It is easier to induce ventricular arrhythmia when QRS
      complexes are wider, irrelevant to left ventricular dysfunction and autonomic
      function of the heart.

PMID- 17205767
TI  - [Right ventricle pacing site optimization guided by intracardiac
      echocardiography].
AB  - Right ventricle outflow tract (RVOT) is an alternative pacing site to right
      ventricle apex (RVA). Intracardiac echocardiography (ICE) is a new method for
      intracardiac structures visualization. THE AIM: is comparison of functional
      effects of DDD permanent ventricular pacing in patients with lead implanted in
      RVA or in RVOT with the use of traditional fluoroscopy or in RVOT guided by ICE.
      MATERIAL AND METHODS: 33 patients with AV block grade I/III no older than 75 y
      (mean age 65,9+/-0,3 years). Group 1: 10 patients with RVA lead implantation.
      Group II: 12 patients with leads implanted in RVOT with the use of ICE. Group
      IlI: 11 patients with lead positioned in RVOT with the use of fluoroscopy. High
      septum was established as an target pacing site for RVOT implantation. On 3 day
      and 3 months after implantation the following parameters were collected: VO2 max,
      6-minute walking test distance, level of NT-proBNP. The comparison of relative
      changes was done, 3 month vs. 3 day for each parameter. RESULTS: Statistically
      significant greater decrease in NT-proBNP was found in Group II in comparison
      with both Group I and Ill (respectively p = 0.021 and p _ 0.034). Significantly
      greater increase in VO2 max was detected in patients Group II comparing to Group
      I (p = 0.047). Moreover it was found that ICE guided implantation is most
      effective in precise lead positioning. CONCLUSION: ICE guided lead localization
      on high interventricular septum seems to have better functional characteristics
      than other right ventricle pacing sites.

PMID- 17205768
TI  - [The value of anorectal manometry as differentiated organic and functional
      disorders in children and youth with chronic constipation].
AB  - Constipation is the most frequent ailment from digestive tract in children and
      youth. Anorectal manometry is no invasion research, contribute to the explanation
      of pathomechanisms of defecation disorders. THE AIM: of our study is the value of
      anorectal manometry in diagnostics organic and functional constipation in
      children and youth. MATRIAL AND METHOD: The study was comprised 100 patients, in
      it 35 girls and 65 boys, aged from 3 to 17 years old (median age 7 years), who
      were diagnosed and treated in Chair and Clinic of Pediatrics, Allergology and
      Gastroenterology by the reason of constipation. The difficulties with
      constipation were kept at least by three months. Among of analyzed patients 64
      came from city and 36 came from the country environment. Transit time was
      measured in all patients by Abrahamsson' method in modification Hinton. In all
      patients was measured also anorectal manometry and rectoscopy with histological
      research. RESULTS: At age group from 3-6 years old and 7-12 years old near 70%
      were boys. At the group 13-17 years old frequently constipation were in girls
      (70%). Majority analyzed with constipation in the three groups came from city
      (group I - 60%, group /II - 71%, group /1/ - 67%). The total colonic transit time
      was prolonged in 50 (50%) patients with constipation, in 50 (50%) transit time
      was normal. In 19 patients was the lack of nerve cells in rectum. In 6 patients
      with the lack of nerve cells in histological research was the lack of rectoanal
      inhibitory reflex in anorectal manometry. In all patients with presence of nerve
      cells was RAIR in anorectal manometry. In 66 (66%) children had normal dynamics
      of defecation. At 34% patients had disturbance of dynamics of defecation (in 21
      patients paradoxical shrink of anorectal sphincter, 13 the lack of sphincters
      relaxation during straining). The organic lesions in anorectal region were in 16
      children with constipation. 84 patients granted criteria of functional disorders
      defecation from 1999 (so called I1 classification of roman functional
      disturbance). There were not observed essential statistically differences in
      frequency paradoxical shrink of sphincter and the lack of sphincters relaxation
      during straining in the group children with organic and functional constipation
      (p > 0.05). We were observed strong relationship important statistically between
      presence nerve cells and presence RAIR (p < or =0.01). CONCLUSION: On the base of
      conducted analysis may be stated at anorectal manometry is useful research in
      differentiating the kind of defecation disorders in children and youth, which can
      limit the range of invasion diagnostic research.

PMID- 17205769
TI  - [Gastric myoelectrical activity in children and youth with dyspeptic symptoms].
AB  - THE AIM: of the study was to analyze gastric myoelectrical activity in children
      and youth with dyspeptic symptoms. MATERIAL AND METHODS: 113 children and youth
      aged 4.5 to 18 years (mean age 13.4 years) with dyspeptic symptoms were enrolled
      into the study. They were divided into 4 groups: group I--30 patients--without
      gastrooesophageal acid reflux GER (-) and Helicobacter pylori infection Hp (-),
      group II--35 patients, GER (+) Hp (-); group III--20 patients, GER (-) Hp (+);
      group IV --28 patients, GER (+) Hp (+). Gastrooesophageal acid reflux was
      recognized using 24-hour pH-metry. Helicobacter pylori infection was diagnosed
      based on histopathological examination of gastric body and/or antrum specimens,
      urease test and (or) C13 urea breath test. Gastric myoelectrical activity was
      performed using multichannel electrogastrography (Medtronic POLYGRAM NETTM). Six
      EGG electrodes were fixed on the subject's abdomen in standard places. Fasting
      EGG was recorded for 30 minutes followed by one hour postprandial recording after
      an ingestion of standard meal. Variables assessed were: dominant frequency (DF),
      the power of the dominant frequency (DP), percentage of bradygastria, normal,
      tachygastria and arrhythmia frequency, dominant frequency instability coefficient
      (DFIC), dominant power instability coefficient (DPIC) recorded from each channel
      (C1, C2, C3, C4) and average percentage slow wave coupling (%SWC) among channels.
      Comparisons were performed using Kruskal-Wallis's test. RESULTS: In comparison to
      group II GER (+) Hp (-) in group I GER (-) Hp (-) were recorded significantly
      higher percentage of bradygastria frequency in C1 and C2 (5% vs 2% and 4% vs. 1%)
      and postprandialy significantly higher percentage of arrhythmia in C4 (18% vs
      13%). In comparison to group Ill GER (-) Hp (+) in group I GER (-) Hp (-) fasting
      were observed significantly lower dominant frequency (2.89 vs 3.07 cpm), higher
      percentage of tachygastria frequency in C1 (3% vs. 1%), lower percentage of
      arrhythmia frequency in C2 (20% vs 29%), higher DPIC in C4 (1.46 vs 1.27), higher
      average percentage %SWC 2-3 (70% vs 59%) and postprandialy lower DFIC in C4 (0.45
      vs 0.54). In comparison to group IV GER (+) Hp (+) in group I GER (-) Hp (-)
      fasting were recorded lower percentage of arrhythmia frequency in C1 and C2 (18%
      vs 27% and 20% vs 30%) and postprandialy lower percentage of arrhythmia frequency
      in C2 (11% vs 17%) and lower DFIC in C2 (0.37 vs 0.48). In comparison to group
      Ill GER (-) Hp (+) in group II GER (+) Hp (-) fasting were observed significantly
      lower percentage of bradygastria frequency in C1 (2% vs 4%), higher DPIC in C2
      (1.87 vs 1.28), higher average percentage %SWC 1-3 and 2-3 (71% vs 63% and 71% vs
      59%) and postprandialy higher percentage of bradygastria frequency in C1 (5% vs
      3%) and higher average percentage %SWC 3-4 (68% vs 58%). In comparison to group
      IV GER (+) Hp (+) in group II GER (+) Hp (-) fasting were recorded significantly
      higher percentage of normal frequency in C1 and C2 (76% vs 68% and 75% vs 67%)
      and higher average percentage %SWC 1-2 (77% vs 69%) and postprandialy
      significantly lower percentage of arrhythmia frequency in C1 (12% vs 18%). In
      comparison to group IV GER (+) Hp (+) in group Ill GER (-) Hp (+) fasting were
      observed significantly higher dominant frequency (3.07 vs. 2.87 cpm, p < or =
      0.01) and lower percentage of tachygastria frequency in C1 (1% vs 2%) and
      postprandialy lower percentage of bradygastria frequency in C1 and C2 (3% vs 5%
      and 3% vs 5%) and lower DFIC in C2 (0.33 vs 0.48). CONCLUSION: In dyspeptic
      children and youth Helicobacter pylori infection and/ or gastrooesophageal acid
      reflux have influence on the gastric myoelectrical activity EGG abnormalities in
      patients with these diseases are varied, mostly preprandialy and recorded from
      proximal part of the stomach.

PMID- 17205770
TI  - [Biochemical bone turnover markers in patients with conventional and
      nonconventional osteosarcoma].
AB  - Biochemical bone turnover markers which reflect bone formation as well as bone
      resorption processes are sensitive indicators of early bone metabolism
      disturbances. They are considered to be useful in diagnosis and treatment of many
      metastatic bone diseases and primary osseous tumours. THE AIM: of the study was
      to assess bone turnover markers in patients with conventional and nonconventional
      osteosarcoma during treatment. MATERIAL AND METHODS: We examined 55 patients (5
      20 years) with osteosarcoma. Among them 91% had conventional and 9% had
      nonconventional histology. Among patients with most frequent conventional
      osteosarcoma distinguished histological subtypes. Bone turnover markers were
      determined in serum by immunoenzymatic assay at diagnosis, during preoperative-
      and postoperative chemotherapy and then after treatment. RESULTS: We found
      different values of bone turnover markers in serum of patients with conventional
      osteosarcoma. At the moment of biopsy the highest value of osteocalcin in
      patients with fibroblastic subtype was observed. The highest activity of bone
      alkaline phosphatase and collagen type I crosslinked C-telopeptide in children
      with osteoblastic subtype of osteosarcoma were obtained. The levels of tested
      parameters decreased about 20-40% during preoperative and postoperative
      chemotherapy, then they increased after treatment first of all in patients with
      chondroblastic subtype (p < 0.05). Next we found that the osteocalcin
      concentration was 4-fold lower, in nonconventional osteosarcoma in comparison to
      the conventional. This marker is stable during treatment and remains unchanged
      after it. Moreover we showed that the changes of the bone alkaline phosphatase
      activity and the collagen type I crosslinked C-telopeptide concentration during
      and after treatment were less dynamic in children with nonconventional
      osteosarcoma. CONCLUSIONS: Observed changes of markers in various histological
      subtypes of osteosarcoma can indicate different rate of their bone turnover.
      Changes observed during treatment are more dynamic in conventional than in
      nonconventional type of osteosarcoma.

PMID- 17205771
TI  - [Comparative retrospective analysis of pain afflictions in patients with lumbar
      discopathy receiving conservative or operative therapies].
AB  - Pain afflictions are the basic problems in patients with discopathy of the lumbar
      backbone. Pain control is the key therapeutic task in patients with a disease of
      the intervertebral disc. Degree of reduction of the pain sensations is one of the
      most important criteria in assessment of the treatment efficacy. THE AIM: of this
      study was to evaluate the pain afflictions in patients with lumbar discopathy
      treated with conservative and operative therapies. MATERIAL AND METHODS: 665
      patients aged between 16 and 76 years with discopathy at L4-L5 and L5-S1 levels
      have been enrolled to the study. In estimated group 348 patients received only a
      conservative therapy whereas 317 patients undergone an operative procedure.
      Analysis has been performed based on pain rating scores: Low Back Pain Rating
      Scale (LBPRS), Japanese Orthopedic Association Low Back Pain Score (JOA-LBPS),
      Domial's pain rating score. RESULTS: Results of performed studies show that
      conservative and operative treatment significantly alleviate pain affliction in
      patients with lumbar discopathy. Complete abatement of pain afflictions more
      frequent refers to operated patients than those only receiving conservative
      therapy. Alleviation of pain afflictions within a period of three years following
      operating procedure is significantly higher than within analogous period of
      conservative treatment. Reduction of pain obtained as a result of surgical
      procedure in higher degree refers to limb than backbone. Treatment method does
      not exert an influence on nature of pain afflictions within distant period.
      CONCLUSIONS: Alleviation of pain afflictions within a period of three years
      following operating procedure is significantly higher than within analogous
      period of conservative treatment. Treatment method does not exert an influence on
      nature of pain afflictions within distant period. Patients at the age of above 50
      notify the higher level of intensity of pain ailments than young patients and
      patients in mid age.

PMID- 17205772
TI  - [Causes of death of patients with systemic sclerosis].
AB  - Systemic sclerosis (SSc) is a chronic, systemic connective tissue disease,
      characterized by progressive skin fibrosis, internal organs and disfunction blood
      vessels. THE AIM: of the study was o analyze death causes in patients with SSc
      and the assessment of relationship between clinical status, immunologic test
      results and survival/mortality of patients with SSc. MATERIAL AND METHODS: Case
      histories of all patients with SSc, hospitalized for six years (since 1'" October
      1999 to 1It October 2005) in Department of Rheumatology and Internal Diseases,
      Medical University of Bialystok, were retrospectively analyzed. Current patients
      status at the end-point of study was estimated during control examination and
      phone contact in selected cases. The time and cause of death was based on autopsy
      results. RESULTS: In study group of 76 patients with SSc, 13 deaths were found
      (17,1%). Death cause analyses revealed that: interstitial lung disease was the
      main cause of death (4/13 - 30%). As a secondary cause of death in these patients
      neoplasms were recognized (3/13 - 23,1%). In all patients with neoplasms
      exudation in pleura was diagnosed. CONCLUSIONS: Pulmonary complications and
      neoplasms are predominant causes of death in patients with SSc. Risk factors of
      death are: pulmonary hypertension and myositis. The presence of exudation in
      pleura in patients with SSc is a bad prognostic symptom and a possible sign of
      neoplastic disease.

PMID- 17205773
TI  - [The personality change in epilepsy patients].
AB  - Personality disorders in epilepsy patients are frequent, and cause behaviour that
      is quite often troublesome for social environment of patients. The peculiarity of
      the clinical picture and mechanism of disorder formation has caused great
      interest. The term 'characteropathy in epilepsia patient', with characteristic
      viscosity as its important basic symptom, was eliminated from present medical
      terminology. Current worldwide international disease classification systems (DSM
      IV and ICD-10) do not distinguish the separate form of personality disorders
      related to epilepsy. THE AIM: of the work is to analyse personality change in
      epilepsy patients on the basis of information from the patients and their
      relatives by means of the Adjective Check List (ACL) by Gough and Heilbrun, with
      taking into consideration the incidence of depression and the phenomenon of 'out
      of-body experience'. MATERIAL AND METHODS: 40 patients with idiopathic
      generalized epilepsy with tonic - clonic seizures in age 19-55 years (mean 28
      years) and 30 persons of age - matched control groups were examined. Each
      examined person and relative filled in ACL form two times in order to answer a
      question about the features of actual and premorbid patient's personality. The
      change of personality was evaluated according to ACL criteria and the
      psychoterapeutic criteria. In analysis were also taken into account the incidence
      of depression and the phenomenon of 'out-of-body experience'. RESULTS: The
      personality change in epilepsy patients was more frequent than in the control
      group and more frequent concerned need scales of ACL (endurance, deference, self-
      and others understanding, and aggression scale). In the grave epilepsy group
      considerable behavioral and interpersonal relationships change (more
      subordination tendency), features of dementia, and often phenomenon 'out-of-body
      experience' were observed. The range of personality change in the mild epilepsy
      group, like in control group, included the adaptation of family functioning
      principles to the patients' needs, the change of patients' emotional reaction and
      the meaning of life. In this group depression was often, but the phenomenon 'out
      of-body experience' hardly ever appeared. CONCLUSIONS: The personality change in
      epilepsy patients was found in more than 80% of patients and concerned need
      scales of ACL (endurance, deference, self- and others understanding and
      aggression scale), and thematic scales (self ideal, self-control, and self
      confidence scale). In the grave epilepsy group considerable behavioral changes,
      features of dementia, and often the phenomenon 'out-of-body experience' were
      observed. In the mild epilepsy group the changes were limited to alter of
      conviction and emotional response, often depression appeared, but hardly ever the
      phenomenon 'out-of-body experience' was observed.

PMID- 17205775
TI  - [Severe sepsis or clinical view of autoaggressive disease. Wegener's
      granulomatosis--case report].
AB  - Each factor infection or non-infection (surgery, burn) can be the cause of
      inflammatory reaction development and in turn releasing of pro- and
      antiinflammatory mediators. Excessive or/and uncontrol releasing of these
      mediators leads to endothelium damage and organ dysfunction. Standard analysis of
      common infection markers, i.e. peripheral blood leukocytes, C-reactive protein,
      reaction of Biernacki measurements, do not allow to distinguish infection and
      noninfection reason of systemic inflammatory response. Procalcitonin is the
      specific marker for bacterial and fungal infection. Its level is low during local
      bacterial and virus infection, autoimmunological diseases, but it is increased at
      the patients with sepsis, severe sepsis. In described case (patient with
      Wegener's granulomatosis) applying procalcitonin measurement and sensitive and
      specific microbiological diagnostic by using bronchio-alveolal lavage leads to
      successful treatment.

PMID- 17205774
TI  - [Sudden cardiac arrest as the first symptom of coronary heart disease--case
      report].
AB  - We describe the patient at whom sudden cardiac arrest was the first symptom of
      coronary heart disease. In the paper, we describe factors which influence the
      effectiveness of resuscitation in out of hospital cardiac arrest. Applying the
      cardiac massage by a bystander, the presence of defibrillation rhythm and short
      period of time to the first defibrillation, determined the survival of the
      patient.

PMID- 17205776
TI  - [Hemorrhage from stomach ulceration in chronically hemodialysed patient after
      planned tonsillectomy].
AB  - We present a chronically hemodialysed patient who developed an acute throat
      hemorrhage after standard tonsillectomy, planned as a standard surgery for
      purulent tonsillitis being contraindication to kidney transplantation in this
      case. Hemorrhage diagnosed firstly as a local post tonsillectomy complication
      proved to be caused by in the acute stomach ulcer. In the discussion we present
      the differentiate diagnosis as well as procedures which should be undertaken in
      hemodialysed patients who develop acute hemorrhage episodes from upper
      respiratory tract after tonsillectomy.

PMID- 17205777
TI  - [Diffuse hyperplastic oncocytosis of the parotid gland].
AB  - An intracellular metabolic disturbance associated with mitochondriopathy, due to
      an age dependent metabolic defect, is suggested to cause metaplasia of salivary
      gland cells into oncocytes. The WHO classification of salivary gland diseases
      considers 3 oncocytic lesions: oncocytosis, oncocytoma and oncocytic carcinoma.
      In case of diffuse hyperplastic oncocytosis of the parotid gland, extensive
      metaplasia of acinic and ductal cells leads to transformation of nearly all cells
      of the gland into oncocytes, which is clinically characterised by swelling of the
      parotid gland, and is an extremely rare condition. A 82-year-old man (the eldest
      of all reported) presented with a 2-month history of increasing diffuse swelling
      of the left parotid gland, 6 cm in diameter. The mass was soft, painless to
      palpation and grew in the superficial lobe of the parotid gland. The patient
      underwent surgical removal of the lesion with wide margins of healthy tissue.
      Histopathological examination of the operative specimen disclosed oncocytosis of
      the salivary gland. The patient has been followed-up for 6 months. He is doing
      well without recurrence. Surgical removal of the diffuse hyperplastic oncocytosis
      of the parotid gland, with indications and extent of the resection like in benign
      tumors, was effective in the presented patient.

PMID- 17205778
TI  - [Biology of tumor necrosis factor type alpha (TNF-alpha)].
AB  - Tumor necrosis factor type alpha (TNF-alpha) is one of 22 TNF superfamily
      ligands. Its synthesis is regulated by expression of gene localized on chromosome
      6. During posttranslation modification the proteolytic cleavage of the 76
      aminoacid domain from the membrane-bound protein occurs with final formation of
      mature, biologically active, secreted TNF-alpha form. The effect on the target
      cells depends on the activation of specific surface receptors: TNFR1--is present
      on most nuclear cells and has affinity to both membrane-bound and secreted forms;
      TNFR2--is localized mostly on fibroblasts, endothelial cells, lymphocytes,
      macrophages, neutrophils and thymocytes, and is activated almost selectively by
      membrane-bound form. Depends on additional factors the TNFR1 activation may
      initiate apoptosis, or activation of pathways which depend on nuclear factor
      kappaB (NFkappaB) and c-Jun N-terminal kinase (JNK). Role of TNFR2 is unclear.
      TNF-a has multidirectional biological activity that include immunomodulation,
      oncostatic, osteolytic, pirogenic, proinflammatory and other effects.

PMID- 17205779
TI  - [The role of integrins in the physiologic and pathogenic processes].
AB  - Cell adhesion molecules (CAM) are a numerous, diverse group of cell surface
      proteins, which are both receptors and ligands for receptors. Their functions
      include adhesion, recognition, cell-cell interaction, and communication between
      mediate cells and extracellular matrix. The following groups of CAM can be
      distinguished: seletins, integrins, cadherins and other isoforms, including CD
      44. Integrins are heterodimers formed from the alpha and beta chains. The a
      subclass is responsible for a specific bond with ligands. It defines the
      specificity of integrins. The 8 chain participates in the integration with
      cytoskeleton ptoteins. It determines the functions of the integrin receptor. The
      best recognized integrins include: integrin beta1, beta2 and beta3. The
      expression and activity of integrins have been found to be affected by a variety
      of factors being either activators or inhibitors. Adhesion molecules (including
      integrins) play a significant role in both physiological processes
      (embryogenesis, organogenesis, the normal growth and tissue development) and
      pathogenic ones. In the latter case, they are particularly involved in
      inflammatory, allergic and neoplastic diseases. The role of integrins is also
      emphasized in organ response to trauma and in skin lesion redevelopment. The
      knowlegde of the integrin molecular basis and that of other adhesion molecules
      can contribute significantly to the creation of new diagnostic and therapeutic
      perspectives. An adequate modification of cellular adhesion constitutes a
      promising way of the pathogenic processes control.

PMID- 17205781
TI  - [The connection between gastroesophageal reflux and airways inflammatory
      diseases].
AB  - It is increasingly suggested a connection between gastroesophageal reflux (GER)
      and bronchial asthma (BA). Coexistence of both these diseases is suggested by
      presence of asthmatics symptoms in non-atopic patients, difficult control and
      resistance of the specific treatment for asthma disease in some patients,
      worsening of respiratory symptoms in circumstances which favored GER. The purpose
      of the paper was presentation of the potential pathogenetic relationships between
      asthma and GER, their clinical manifestations and epidemiology in different age
      groups, and finally confirmation of the effectiveness of treatments for
      gastroesophageal reflux (especially using protonic pumps inhibitors) in terms of
      their benefit on asthma course, both in children as in adults.

PMID- 17205780
TI  - [Drugs affecting thyroid--part II].
AB  - The use of several groups of medications may result in thyroid dysfunction. So
      far the best known medication is amiodarone. The role of other medications and
      diagnostic agents in causing thyroid dysfunction is quite often forgotten. We
      presented medications and diagnostic agents commonly used in medical day-to-day
      practice. We described other than amiodarone iodinated agents and quoted recently
      published European guidelines in using iodinate contrast agents. We focused on
      lithium and psychiatric drugs and mechanism of their toxic impact on thyroid
      gland. These agents are important as they are applied for years (including
      children). At the end the impact of cytokines on thyroid gland was discussed,
      medications ever more widely applied in anti-viral and anti-neoplastic therapy.

PMID- 17205782
TI  - [Biochemical basic of alcoholic liver injury].
AB  - The liver is the main place of ethanol oxidation and is especially sensitive to
      the toxic effects of alcohol. Alcoholic liver disease is caused by chronic
      alcohol abuse. The article presents the negative effect of alcohol and its
      metabolites on the different biochemical processes in the liver.

PMID- 17205783
TI  - [The presence of bacteriophages in human feces and their potential importance].
AB  - Bacteriophages are widely distributed throughout the environment as well as in
      the bodies of humans and animals (feces, urine, saliva, sputum). Higher presence
      of Escherichia coli phages compared with Bacteroides fragilis and Salmonella
      phages was noticed in the feces of healthy human individuals and patients, mainly
      those with gastro-intestinal tract diseases. A strict correlation exists between
      the number of bacteria and of phages in the feces of healthy individuals as well
      as of patients with different diseases. The presence of phages in human feces
      correlates with the character of the coexisting disease. The frequency of phages
      in the feces depends on the different indicator bacterial host strains and the
      numbers of indicator strains. The role of bacteriophages in protecting against
      pathogenic microorganisms and controlling bacterial flora in the human organism
      is of major significance.

PMID- 17205784
TI  - [Genetic factors in susceptibility to age- and noise-related hearing loss].
AB  - Individual susceptibility to age-related hearing loss (AHL) and noise-induced
      hearing loss (NIHL) varies greatly, and this inter-individual variation is due to
      an interaction of environmental factors, individual factors, and susceptibility
      genes. Majority of studies on susceptibility genes for AHL and NIHL have been
      performed in mice model. These findings suggest the role of the same genes in the
      development of AHL and NIHL, the more so as the pathogenesis of both diseases is
      similar with a crucial role of oxidative stress. The alleles responsible for AHL
      have been localized to the chromosome 10 (Ahl gene). Ahl-/- mice develop hearing
      impairment at early age and are also oversensitive to noise. Ahl gene is a
      recessive gene and it is probably responsible for the synthesis of cell junction
      proteins. In mice ahl codes for cadherin (CDH) proteins. The cadherin of interest
      is named otocadherin or CDH23, and it is localized to the links between
      stereocilia of hair cells. A hypomorphic 753G>A single nucleotide polymorphism
      (SNP) in Cdh 23 is associated with AHL, and the 753A variant is also correlated
      with susceptibility to NIHL. An increased susceptibility to AHL and NIHL may rely
      on the SNPs of several other genes, including the groups of oxidative stress
      genes, K+ ions recycling genes, monogenic deafness genes (including Connexin 26
      gene, which mutation is responsible for the most frequent hereditary deafness in
      Caucasians), as well as mitochondrial genes. Several oxidative stress enzyme
      (sod1-/-, gpx -/-) knock-out mice have been shown to be more susceptible to NIHL
      than wild strains. Current large-scale cohort studies on AHL and NIHL performed
      under the European projects in between-lab collaboration along with a dynamic
      progress in the field of genetics of deafness open up new opportunities to find
      human AHL and NIHL susceptibility genes and develop methods for AHUNIHL
      treatment.

PMID- 17205785
TI  - [Melatonin and bone status].
AB  - This paper reviews the findings accumulated on the role of melatonin (MEL) on
      bone status and the role of RANKL/RANK/OPG system (receptor activator of nuclear
      factor-kappa B ligand/ receptor activator of nuclear factor-kappa
      B/osteoprotegerin) in this mechanism. Recent studies indicate that MEL may
      influence on the bone directly by acting osteoclasts and perhaps osteoblasts,
      and/or indirectly by down-regulating RANK-mediated osteoclast formation and
      activation. Induced by MEL, changes in the level of factors which play a role in
      the regulation of bone remodelling, may secondarily (directly and/or indirectly
      through RANKURANK/OPG system) influence on bone status.

PMID- 17205786
TI  - [Specific of pharmacotherapy management in back pain among the elderly].
AB  - Back pain is one of the main reasons for physical disability among the elderly.
      The most frequent cause of the pain among this group is the degenerative disease.
      The larger part in causes of low back pain among the elderly has metabolic
      (osteoporosis) and neoplastic diseases. Pharmacological treatment of the back
      pain requires to take into consideration its etiology, course, specific
      biological features of the organism ageing, pain chronification features and
      extrasomatic influences. Environmental influences and additional diseases are not
      insignificant as well. The aforementioned factors determine limitations in using
      painkillers. The limitations concern quality area (e.g. medicine group, chosen
      pharmaceutical agents, way of medicine administration) and quantity area (e.g.
      drug dosage, time of application). The specified differences in etiology, course
      of low back pain and drug absorption and excretion among the elderly are not
      sufficiently taken into consideration. It becomes the cause of side effects of
      the used drugs, lack of treatment efficiency and as a result deterioration of
      life quality. To improve efficiency in low back pain treatment, the authors
      reviewed the literature and presented their own opinions on using different
      groups of drugs and limits of pharmacotherapy among the elderly.

PMID- 17205787
TI  - [Placental corticotropin releasing-hormone and urocortin--possible role in
      mechanism of preterm labor].
AB  - The preterm labor is a very important clinical problem, both in the diagnostic,
      prophylactic and therapeutic aspect. It is the leading cause of prenatal
      morbidity and mortality. Despite of numerous studies and hypotheses mechanisms
      responsible for human parturition and pre-term labor are unclear. More than 30
      years ago it was documented, that placenta is the important source of hormones,
      cytokins and growth factors. Corticotropin-relasing hormone (CRH) and urocortin
      (new ligand of CRH receptor) secreted during pregnancy by placenta, chorion,
      amnion and uterine decidua probably plays important role in human parturition and
      preterm labor. Possibly the combined hormonal markers profile to predict preterm
      labor can be used in the future.

PMID- 17205788
TI  - [Music therapy as a part of complex healing].
AB  - Music therapy is a method which takes the adventage of therapeutic influence of
      musie on psychological and somatic sphere of the human body. Its therapeutic
      properties are more and more used. Current scientific research have proved its
      modifying influence on vegetative, circulatory, respiratory and endocrine
      systems. Works devoted to the effects of musie on the patients' psychological
      sphere have also confirmed that it reduces psychopathologic symptoms (anxiety and
      depression), improves self-rating, influences quality and disorders of sleep,
      reduces pain, improves moral immunity and patients' openness, readiness, co
      operation in treatment process. Music therapy is treated as a method which
      complements conventional treatment and makes up part of an integral whole
      together with physiotherapy, kinesitherapy and recuperation.

PMID- 17205789
TI  - [Metabolic integration of organisms within symbiotic systems].
AB  - Adaptation of organisms to coexisence in symbiotic systems is usually related to
      significant metabolic changes resulting in the integration of the biochemical
      pathways of the partners. In the symbioses between plants and nitrogen-fixing
      organisms, between heterotrophic and autotrophic organisms, as well as between
      animals and microorganisms providing the consumption of plant biomass, the
      systems of C- and N-metabolism, controlling the utilization of various sources of
      nitrogen (N2, organic and inorganic compounds, metabolic waste of the host) and
      carbon (CO2, plant polymers), of the partners are tightly integrated. Bilateral
      biochemical links between partners are typical to mutualistic symbioses (wherein
      biotrophic nutrition predominates, in some cases including necrotrophy of
      secondary origin). In antagonistic symbioses, unilateral links predominate,
      though active assimilation of the pathogen's secondary metabolites by the host is
      also possible. In most mutualistic symbioses, integrated metabolic ties have
      derived from trophic chains in biocenoses (syntrophic consortia, "predator-prey"
      systems), but not from the systems where the pathogens consume host metabolites.
      At the same time, molecular analysis of symbiotic interactions has shown that
      symbioses considerably differ from biocenoses, where the cycling of nutrients and
      energy implies no functional integration of the partner's genes.

PMID- 17205790
TI  - [Comparative analysis of the energy flows in the ecosystem of a small eutrophic
      lake during three vegetation seasons (balance model)].
AB  - Seasonal energy flows were calculated, based on a simulation balance model, from
      unique data collected during three vegatation seasons, 1986-1988, in the
      ecosystem of the Lake Bolshoy Okunyonok, Leningrad province. The model is based
      on principles developed by G.G. Winberg's school of production hydrobiology and
      was described in detail in an earlier work (Kazantseva, 2003). Analysis and
      comparison of the results showed that certain regularities of energy
      transformation processes in any lake ecosystem are apparent in spite of natural
      differences determined by differences in the environment properties and the
      levels of development of the ecosystem components. For instance, the extreme
      importance of the bacteriadetritus element in the food chains of water-body was
      confirmed. Broad spectrum of food and considerable changes in food composition
      during a vegetation season were clearly shown for most hydrobionts. The degree of
      consumption was estimated for the production of the organisms at each trophic
      level. It was shown that all the consumers eat away ca. 50-60 per cent of the
      production of the forage phytoplankton, 90 per cent of the production of non
      predatory benthos, and 20-50 per cent of the production of the other trophic
      groups during a season. The proposed coefficient of energy transformation, CET(s,
      k) = Ps(k)/Pk, where Ps(k) in the production of the consumer s created by
      consuming the source k, and Pk is the production of the source itself, proved to
      be more stable than the generally accepted coefficient q = Ps/Ps -1.

PMID- 17205791
TI  - [Principal stages in the Cenozoic diversification of shallow-water molluscan
      faunas in the North Pacific].
AB  - Cluster analysis of bivalve species recorded in Cenozoic deposits in Sakhalin
      Island, western Kamchatka, Hokkaido, and California was used to determine
      geological age of the modem North Pacific biogeographic region and its
      constituent subregions (Japan-Mandchurian, Beringian, and Oregon-Sitkan). The
      North Pacific region developed during the Paleogene-Neogene transition due to
      Drake Passage opening to deep-water movement, formation of the deep-water
      Antarctic Circumpolar Current, and the change in climate from greenhouse to
      psychospheric. Differentiation of the three subregions within the North Pacific
      Region seems to have occurred in late Miocene-early Pliocene, about 5.6 millions
      years ago and was probably due to the flooding of the Bering Land Bridge and
      development of the present configuration of circulation in the North Pacific. In
      the Northwest Pacific, during Paleogene and early Neogene, the faunal
      diversification occurred more rapidly and was more extensive than in the
      Northeast Pacific.

PMID- 17205792
TI  - [Relation of the snow cover to the structure of vegatation in the alpine
      communities of the eastern Tsinghai-Tibet Plateau].
AB  - The type of snow cover considerably influences the sctructure of vegetation and
      production-related processes in alpine communities of diverse regions. The
      relation of snow cover thickness to the structure of apline plant communities in
      the eastern Tsinghai-Tibet Plateau (Sichuan, People's Republic of China) was
      studied by analyzing the vegetation in 251 sample areas grouped in five transects
      along the gradient of mesotopographic conditions and wintertime snow cover
      thickness. Considerable differentiation of plant communities related to snow
      cover thickness in revealed along the line from the northern to the southern
      slope. It is shown that the influence of snow cover on the distribution of
      particular plant species is significantly greater than the influence of soil
      properties (pH, content of humus, total phosphorus, potassium, and ammonia
      nitrogen in the upper strata of soil). Among the 56 herbaceous plant species and
      7 shrub species studied, 52 herbaceous and all the 7 shrub species showed
      significant (P < 0.05) correlation (positive or negative) to snow cover
      thickness. Snow cover thickness appeared also significantly correlated to a
      number of soil properties: soil thickness, content of water, total phosphorus,
      and humus. But, in contrast to the alpine communities of the Caucasus and the
      Alps, no considerable acidification of the soil under snowflakes, due to
      perpetual removal of cations by melt water, was observed.

PMID- 17205793
TI  - [Competition of two marine diatom algae for urea and nitrate nitrogen under three
      levels of irradiance].
AB  - Biomass dynamics of the plankton diatoms Thalassiosira weissflogii and Pseudo
      nitzschia delicatissima were analyzed in batch mono- and mixed cultures grown on
      media with urea or nitrate as the sources of nitrogen, under irradiance 13, 38,
      and 115 microE/(m(2) x s). At the initial enrichment, nitrogen concentration was
      0.18 mmol, and the nitrogen : phosphorus ratio was 5 : 1. The mechanisms of
      competition for the limiting resource satisfactorily described the interactions
      between the algae grown on urea. Competitive ability of algae was characterised
      according to the value of competitive eddect (CE), which was calculated as the
      ratio of growth rate and accumulated biomass decrease in mixed culture to that in
      monoculture CE of algae grown on urea increased with the increasing of irradiance
      and was lower than that of algae grown on nitrate. CE of P. delicatissima was
      higher than that T. weissflogii, independently of the source of nigrogen and the
      level of irradiance. At 38 and 115 microE/(m(2) x s) the growth of T. weissflogii
      ceased earlier than that of P. delicatissima, independently of the source o
      nitrogen. At 13 microE/(m(2) x s) the growth of P. delicatissima ceased earlier
      than of T. weissflogii in on cultures grown urea, but the growth of T.
      weissflogii was the first to cease on nitrate. The competition revealed in
      experimental communities for the nitrogen of urea between plankton algae gives
      reasons to suggest that in natural communities plankton algae also compere under
      inorganic nitrogen deficiency and organic nitrogen abundance.

PMID- 17205794
TI  - [Fungal lycopene: the biotechnology of its production and prospects for its
      application in medicine].
AB  - This article deals with the lycopene of mycelial fungi. It pays special attention
      to its physical and chemical properties, occurrence in nature, biological
      functions, and the biotechnology of lycopene production. Data are presented
      concerning the medically important properties of lycopene and the drug
      Mycolycopene prepared on its basis. Its prospective use in the therapy of
      prostate cancers is discussed.

PMID- 17205795
TI  - [Alternative pathways of nitric oxide formation in lactobacilli: EPR evidence for
      nitric oxide synthase activity].
AB  - The study of the ability of Lactobacillus plantarum 8P-A3 to synthesize nitric
      oxide (NO) showed that this strain lacks nitrite reductase. However, analysis by
      the EPR method revealed the presence of nitric oxide synthase activity in this
      strain. Like mammalian nitric oxide synthase, lactobacillar NO synthase is
      involved in the formation of nitric oxide from L-arginine. L. plantarum 8P-A3
      does not produce NO in the course of denitrification process. The regulatory role
      of NO in symbiotic bacteria is discussed.

PMID- 17205796
TI  - [Comparative analysis of glycogen and trehalose accumulation in methylotrophic
      and nonmethylotrophic yeasts].
AB  - Trehalose and glycogen accumulate in certain yeast species when they are exposed
      to unfavorable growth conditions. Accumulations of these reserve carbohydrates in
      yeasts provide resistance to stress conditions. The results of this study
      indicate that certain Pichia species do not accumulate high levels of glycogen
      and trehalose under normal growth conditions. However, depending on the Pichia
      species, both saccharides accumulate at high levels when the Pichia cells are
      exposed to unfavorable or stress-inducing growth conditions. Growth on glycerol
      or methanol mostly led to trehalose accumulation in Pichia species tested in this
      study. It was shown that the metabolic pathways for glycogen and trehalose
      biosynthesis are present in Pichia species. However, it appears that the
      biosynthesis of trehalose and glycogen may be regulated in different manners in
      Pichia species than in the yeast S. cerevisiae.

PMID- 17205797
TI  - [The fungus Penicillium variabile sopp 1912 isolated from permafrost deposits as
      a producer of rugulovasines].
AB  - It has been established that relict fungi Penicillium variabile Sopp can
      synthesize clavine alkaloids, rugulovasines A and B, which are revealed in this
      species for the first time. Submerged cultivation of the strain-producer revealed
      several microcycles of conidia formation. The synthesis of alkaloids was also of
      a cyclic character. The synchronism beween the cycles of rugulovasine
      biosynthesis and conidia formation was revealed. Zinc ions stimulated fungal
      growth but had a negative effect on the biosynthesis of rugulovasines.

PMID- 17205798
TI  - [Extracellular proteinases of filamentous fungi as potential markers of
      phytopathogenesis].
AB  - The presence of proteins in the culture liquid of filamentous fungi under study
      was found to induce the secretion of proteinases. The inhibitory analysis of the
      major extracellular proteinases of the saprotrophic fungus Trichoderma harzianum
      and the phytopathogenic fungus Alternaria alternata showed that they both belong
      to the group of serine proteinases. The substrate specificity of these
      proteinases and their sensitivity to inhibitors suggest that the enzyme of T.
      harzianum is a subtilisin-like proteinase and the enzyme of A. alternata is a
      trypsin-like proteinase. This difference between the proteinases may reflect the
      physiological difference between their producers (saprotroph and phytopathogen).

PMID- 17205799
TI  - [Response of microbial communities of Lake Baikal to extreme temperatures].
AB  - The survival rate, metabolic activity, and ability for growth of microbial
      communities of Lake Baikal after exposure to extremely low temperatures (freeze
      thawing) for different lengths of time have been first studied. It has been shown
      that short-term freezing (1-3 days) inhibits the growth and activity of microbial
      communities. The quantity of microorganisms increased after 7- and 15-day
      freezing. In the periods of maximums, the total number of microorganisms in the
      test samples was twice as high as in the control. It was established that after
      more prolonged freezing the microorganisms required more time after thawing to
      adapt to new conditions. In the variants with 7- and 15-day freezing, the
      activities of defrosted microbial communities were three or more times higher
      than in the control. The survival rate and activity of Baikal microorganisms
      after freeze-thawing confirms the fact that the Baikal microbial communities are
      highly resistant to this type of stress impact.

PMID- 17205800
TI  - [An efficient mutational method for photosynthetic bacteria].
AB  - The pigment and auxotrophic mutants of Rhodobacter sphaeroides Y6 were obtained
      by treatment with ethyl methanesulfonate (EMS) followed by lithium chloride
      (LiCI). Treatment with 0.081 M EPS and subsequent treatment with 0.071 M LiCI
      resulted in 12% higher frequency of pigment mutations than application of 0.081 M
      EMS alone; the frequency of auxotrophic mutations increased 2.5-fold when
      treatment with lithium chloride was applied. A blue shift 10 nm was recorded in
      the absorption spectrum of carotenoids form YM5-3 green mutant; considerable
      accumulation of neurosporine was revealed by HPLC and mass spectrometry. The
      method is efficient for isolating mutants of photosynthetic bacteria.

PMID- 17205801
TI  - [The first protein map of Synechococcus sp. strain PCC 7942].
AB  - The first protein map was developed of Synechococcus sp. strain PCC 7942, a model
      organism for studies of photosynthesis, prokaryotic circadian rhythms, cell
      division, carbon-concentrating mechanisms, and adaptive responses to a variety of
      stresses. The proteome was analyzed by two-dimensional gel electrophoresis with
      subsequent MALDI-TOF mass spectroscopy and database analysis. Of the 140 analyzed
      protein spots, 110 were successfully identified as 62 different proteins, many of
      which occurred as multiple spots on the gel. The identified proteins participate
      in the major metabolic and cellular processes in cyanobacterial cells during the
      exponential growth phase. In addition, 14 proteins which were previously either
      unknown or considered to be hypothetical were shown to be true gene products in
      Synechococcus sp. strain PCC 7942. These results may be helpful for the
      annotation of the recently sequenced genome of this cyanobacterium, as well as
      for biochemical and physiological studies of Synechococcus.

PMID- 17205802
TI  - [Geoalkalibacter ferrihydriticus gen. nov., sp. nov., the first alkaliphilic
      representative of the family Geobacteraceae, isolated from a soda lake].
AB  - Investigation of iron reduction in bottom sediments of alkaline soda lakes
      resulted in the isolation of a new obligately anaerobic iron-reducing bacterium,
      strain Z-0531, from Lake Khadyn (Tuva Republic, Russia) sediment samples. The
      cells of strain Z-0531 are short (1.0-1.5 by 0.3-0.5 microm), motile, non-spore
      forming, gram-negative rods. The isolate is an obligate alkaliphile, developing
      in the pH range of 7.8-10.0, with an optimum at pH 8.6. It does not require NaCl
      but grows at NaCl concentrations of 0-50 g/1l. It can oxidize acetate with such
      electron acceptors as amorphous Fe(llI) hydroxide (AFH), EDTA-Fe(III),
      anthraquinone-2,6-disulfonate (quinone), Mn(IV), and S(0). On media with EDTA
      Fe(III), the isolate can oxidize, apart from acetate, ethanol, pyruvate, oxalate,
      arginine, tartrate, lactate, propionate, and serine. H2 is not utilized. The
      reduced products formed during growth with AFH are siderite or magnetite,
      depending on the growth conditions. The isolate is incapable of fermenting
      sugars, peptides, and amino acids. Yeast extract or vitamins are required as
      growth factors. The organism is capable of dinitrogen fixation and harbors the
      nifH gene. The DNA G+C content is 55.3 mol %. 16S rRNA analysis places strain Z
      0531 into the family Geobacteraceae. Its closest relative (93% similarity) is
      Desulfuromonas palmitatis. Based on phenotypic distinctions and phylogenetic
      position, it is proposed that strain Z-0531 be assigned to the new genus and
      species Geoalkalibacter ferrihydriticus gen. nov., sp. nov.

PMID- 17205803
TI  - [Effect of hydrogen concentration on the hydrogenotrophic methanogenic community
      structure studied by T-RELP analysis of 16S rRNA gene amplicons].
AB  - Analysis of length polymorphism of 16S rRNA genes terminal restriction fragments
      (T-RFLP analysis) was used to monitor the changes in the composition of the
      population of methanogens in enrichment cultures under high and low hydrogen
      concentrations. Hydrogen concentration was shown to determine the structure of a
      methanogenic community. High hydrogen concentration probably favors the hydrogen-
      and acetate-utilizing representatives of Methanosarcinaceae, while a more diverse
      methanogenic community is favored by low hydrogen concentrations.

PMID- 17205804
TI  - [Classification of Methylomonas rubra sp. nov].
AB  - Strain Methylomonas rubra 15sh(T), deposited in several collections of
      microorganisms (NCIMB 11913(T) = UCM B-3075(T) = ACM 3303(T)), is the subject of
      numerous studies. However, the name of this strain is not valid, primarily due to
      the phenotypic similarity of the species M. rubra to the species M. methanica.
      The results of the present study and data available in the literature indicate
      that M. rubra deserves the status of a separate species. Strains of M. rubra
      differ from strains of M. methanica in a number of properties, such as the
      ability to reduce nitrates to nitrites, the structure of intracytoplasmic
      membranes, and the presence of a new coenzyme Q. The distinctions between the
      species M. rubra and M. methanica were confirmed by comparison of electrophoretic
      patterns of their cellular proteins, by results of DNA-DNA hybridization, and by
      the data from 16S rRNA gene sequencing (the level of phylogenetic homology
      between these two species was below 95%). Phylogenetic and phenotypic analyses
      showed that strains of M. rubra cannot be assigned to any species of the genus
      Methylomonas. Results of polyphasic analysis suggest an independent taxonomic
      status of strain Methylomonas rubra 15sh(T). This paper contains description of
      Methylomonas rubra sp. nov. with the type strain 15sh(T) = NCIMB 11913T = UCM B
      3075(T) = ACM 3303(T). The nucleotide sequence of the 16S rRNA gene of strain
      15sh(T) has been deposited with the GenBank database under the accession number
      AY995198.

PMID- 17205805
TI  - [Phylogenetic characterization of endosymbionts of the hydrothermal vent mussel
      Bathymodiolus azoricus by analysis of the 16S rRNA, pmoL, and cbbA genes].
AB  - In order to assess the phylogenetic diversity of the endosymbiotic microbial
      community of the gills of marine shellfish Bathymodiolus azoricus, total DNA was
      extracted from the gills. The PCR fragments corresponding to the genes encoding
      16S rRNA, ribulose-bisphosphate carboxylase (cbbL), and particulate methane
      monooxygenase (pmoA) were amplified, cloned, and sequenced. For the 16S rDNA
      genes, only one phylotype was revealed; it belonged to the cluster of Mytilidae
      thiotrophic symbionts within the Gammaproteobacteria. For the RuBisCO genes, two
      phylotypes were found, both belonging to Gammaproteobacteria. One of them was
      closely related to the previously known mytilid symbiont, the other, to a
      pogonophore symbiont, presumably a methanotrophic bacterium. One phylotype of
      particulate methane oxygenase genes was also revealed; this finding indicated the
      presence of a methanotrophic symbiont. Phylogenetic analysis of the pmoA placed
      this endosymbiont within the Gammaproteobacteria, in a cluster including the
      methanotrophic bacterial genus Methylobacter and other methanotrophic
      Bathymodiolus gill symbionts. These results provide evidence for the existence of
      two types of endosymbionts (thioautotrophic and methanotrophic) in the gills of
      B. azoricus and demonstrate that, apart from the phylogenetic analysis of 16S
      rRNA genes, parallel analysis of functional genes is essential.

PMID- 17205806
TI  - [The ratio of fungi and bacteria in the biomass of different types of soil
      determined by selective inhibition].
AB  - Tundra, chernozem (virgin and arable), sod-podzolic (coniferous forest, meadow,
      and arable), and grey forest (larch forest) soils were used to separate the
      contributions of fungi and bacteria to substrate-induced respiration (SIR) with
      the help of antibiotics. For soils with a high content of organic matter (tundra
      and chernozem: 12 and 8%, respectively), the procedure of selective inhibition of
      SIR has been optimized. The optimized procedure includes the application of high
      concentrations of streptomycin (50-120 mg/g of soil) and cycloheximide (50-80
      mg/g of soil) and decreasing the weight of the analyzed soil sample. Soils under
      study have shown the predominant contribution of fungi (63-82%) to the total SIR.
      The fungal-bacterial ratio in the soils of natural ecosystems (0-5 cm, without
      litter) was 4.32, 2.19, 1.5, and 1.5 for tundra soil, virgin chernozem,
      coniferous (sod-podzolic soil), and larch (grey forest soil) forests,
      respectively. The lower layers of sod-podzolic (5-10 cm) and grey forest (48-58
      cm) soils showed a decrease in the fungal and increase in the bacterial component
      in the total SIR.

PMID- 17205807
TI  - [Interrelationships between yeast fungi and collembolans in soil].
AB  - The possibility of feeding on green and newly fallen leaves of the small-leaved
      lime Tilia cordata was studied for the collembolans Protaphorura armata and
      Vertagopus pseudocinereus. Young leaves grown under sterile conditions and almost
      free of yeast fungi were established to be toxic to the collembolan V.
      pseudocinereus: feeding on them led to the death of the animals. Leaves grown
      under natural conditions were nontoxic: when used by the collembolans as feed,
      they provided for collembolan growth and fecundity. Feeding preferences of the
      collembolans in relation to the yeasts attributed to different ecomorphs
      epiphytes, litter saprophytes, pedobionts, and saccharobionts-were studied. Of
      the 24 yeast strains isolated from plant green parts, litter, and soil and
      assigned to eight species, no strain was revealed that was not used by the
      collembolans. However, certain yeast strains were preferable for the
      collembolans. The population of the V. pseudocinereus collembolans feeding on the
      yeast Rhodotorula glutinis (nss 31-4) exceeded that grown on Cryptococcus
      terricola (2044) 1.5-fold. Thus, the collembolans have feeding preferences in
      relation to yeast fungi, as was shown earlier for mycelial micromycetes. The
      possible mechanisms of the feeding preferences of the collembolans in relation to
      yeasts are discussed.

PMID- 17205808
TI  - [High abundance of planctomycetes in anoxic layers of a Sphagnum peat bog].
AB  - The depth distribution of planctomycete abundance has been examined in six
      different sites of the Sphagnum peat bog in Bakchar, Tomsk oblast, Russia. In
      situ hybridization of peat with the fluorescently labeled oligonucleotide probes
      PLA46 and PLA886, reported to be group-specific for representatives of the phylum
      Planctomycetes, revealed two distinct population maxima of these bacteria in all
      of the profiles examined. The first population maximum was detected in the
      uppermost, oxic layer of the bog profile, while the second maximum was located at
      a depth of 30 cm below the water table level. The population sizes of
      planctomycetes in the uppermost layer and at a depth of 30 cm were of the same
      order of magnitude and comprised 0.5-1.5 x 10(7) and 0.4-0.7 x 10(7) cells per g
      of wet peat, respectively. Only 25-30% of the total number of planctomycete cells
      in the anoxic layer could be detected if the probe PLA886, whose target
      specificity is restricted to taxonomically characterized aerobic planctomycetes
      of the genera Gemmata, Planctomyces, Pirellula, and Isosphaera, was used alone.
      Other planctomycete cells in this layer were detected only with the probe PLA46,
      which possesses a much wider scope. This suggests the affiliation of these
      organisms with a yet undescribed phylogenetic subgroup within the Planctomycetes.

PMID- 17205809
TI  - [Sulfate reduction and methanogenesis in the Shira and Shunet meromictic lakes
      (Khakass Republic, Russia)].
AB  - The biogeochemical and molecular biological study of the chemocline and sediments
      of saline meromictic lakes Shira and Shunet (Khakass Republic, Russia) was
      performed. A marked increase in the rates of sulfate reduction and methanogenesis
      was revealed at the medium depths of the chemocline. The rates of these processes
      in the bottom sediments decreased with depth. The numbers of Bacteria, Archaea,
      and of sulfate-reducing bacteria (SRB) were determined by fluorescence in situ
      hybridization with rRNA specific oligonucleotide probes labeled with horseradish
      peroxidase and subsequent tyramide signal amplification. In the chemocline, both
      the total microbial numbers and those of Bacteria were shown to increase with
      depth. The archaea and SRB were present in almost equal numbers. In the lake
      sediments, a drastic decrease in microbial numbers with depth was revealed. SRB
      were found to prevail in the upper sediment layer and archaea in the lower one.
      This finding correlates with the measured rates of sulfate reduction and
      methanogenesis.

PMID- 17205810
TI  - [Distribution and activity of microorganisms in the deep repository for liquid
      radioactive waste at the Siberian Chemical Combine].
AB  - The physicochemical conditions, composition of microbial communities, and the
      rates of anaerobic processes in the deep sandy horizons used as a repository for
      liquid radioactive wastes (LRW) at the Siberian Chemical Combine (Seversk, Tomsk
      oblast), were studied. Formation waters from the observation wells drilled into
      the production horizons of the radioactive waste disposal site were found to be
      inhabited by microorganisms of different physiological groups, including aerobic
      organotrophs, anaerobic fermentative, denitrifying, sulfate-reducing, and
      methanogenic bacteria. The density of microbial population, as determined by
      cultural methods, was low and usually did not exceed 10(4) cells/ml. Enrichment
      cultures of microorganisms producing gases (hydrogen, methane, carbon dioxide,
      and hydrogen sulfide) and capable of participation in the precipitation of metal
      sulfides were obtained from the waters of production horizons. The contemporary
      processes of sulfate reduction and methanogenesis were assayed; the rates of
      these terminal processes of organic matter destruction were found to be low. The
      denitrifying bacteria from the underground repository were capable of reducing
      the nitrates contained in the wastes, provided sources of energy and biogenic
      elements were available. Biosorption of radionuclides by the biomass of aerobic
      bacteria isolated from groundwater was demonstrated. The results obtained give us
      insight into the functional structure of the microbial community inhabiting the
      waters of repository production horizons. This study indicates that the numbers
      and activity of microbial cells are low both inside and outside the zone of
      radioactive waste dispersion, in spite of the long period of waste discharge.

PMID- 17205811
TI  - [Characterization of extremely halophilic archaea isolated from saline
      environment in different parts of Turkey].
AB  - Ninety-five extremely halophilic strains were isolated from six distinct saline
      regions of Turkey by using complex medium containing 25% NaCl. The selected
      regions are Tuz Golu (salt lake), Ankara; Aci Lake, Denizli; Salda Lake, Denizli;
      Seyfe Lake, Kirsehir; Tuzla Lake, Kayseri; and Bolluk Lake, Konya. The isolated
      strains were tested for motility, Gram reaction, cell and colony morphologies,
      pigmentation, biochemical characteristics, and antibiotic sensitivities.
      According to membrane glycerol diether moieties and antibiotic susceptibilities,
      all isolated strains were found to belong to the domain Archaea. All isolates
      were examined for the presence of plasmids by agarose gel electrophoresis and it
      was established that most isolates contained plasmids that varied in number and
      whose molecular sizes ranged from 1 to 36.9 kbp. Whole-cell protein profiles from
      isolates were analyzed by SDS-PAGE and a similarity dendogram was constructed
      using the UPGMA method. Significant similarities and differences were observed
      among the isolates. The strains were clustered in eight groups and ten of our
      isolates were placed in the same group with the standard strains. The current
      study represents the first isolation and characterization of such a large
      collection of archeal strains from Turkey.

PMID- 17205812
TI  - [Spectral properties of viable ancient green algae from arctic permafrost].

PMID- 17205813
TI  - [Computer system for image analysis of fluorescently stained bacteria].

PMID- 17205814
TI  - [Prospective, multi-centered, randomized and controlled trial on effect of Shenle
      Capsule in treating patients with IgA nephropathy of Fei-Pi qi-deficiency
      syndrome].
AB  - OBJECTIVE: To observe the effect and safety of Chinese compound Shenle Capsule
      (SC) in treating IgA nephropathy patients of Fei-Pi qi-deficiency syndrome
      (FPQD). METHODS: A prospective, multi-centered, randomized, double-blinded,
      double-mimetic, controlled trial was conducted in 70 IgA nephropathy patients of
      FPQD syndrome, who were randomly assigned to two groups treated with SC and
      fosinopril respectively for 12 weeks. The changes of TCM syndrome score, 24 h
      urine protein quantity (UP), serum creatinine (SCr), hepatic function before and
      after treatment and the adverse reaction were observed. RESULTS: Compared with
      those before treatment, the level of UP and the TCM syndrome scores decreased
      significantly in both groups (P < 0.05 or P < 0.01), while the level of albumin
      increased significantly after treatment, and the level of total cholesterol,
      triglycerid and renal function remained unchanged (P > 0.05). There was no
      significant difference in all the above parameters between the two groups.
      According to the curative criterion for Chinese medicine and Western medicine,
      the total effective rate was 83.3% and 66.7% respectively in the SC treated
      patients, 82.4% and 58.8% respectively in the fosinopril treated patients,
      showing insignificant difference between them. In addition, no severe adverse
      event was found. CONCLUSION: SC treatment showed effects similar to that of
      fosinopril in reducing proteinuria and improving TCM syndrome in IgA nephropathy
      patients of FPQD syndrome, and could be well tolerated by patients.

PMID- 17205815
TI  - [Effects of modified Wuzi Yanzong Granule on memory ability and volume of
      hippocampus measured by MRI in patients with mild cognitive impairment].
AB  - OBJECTIVE: To observe the effect of modified Wuzi Yanzong Granule (WYG) on memory
      ability and volume of hippocampus measured by magnetic resonance imaging (MRI) in
      patients with mild cognitive impairment (MCI). METHODS: According to the
      international accepted diagnostic criteria, 36 MCI patients were selected and
      randomly assigned to two groups equally, the treated group treated with WYG and
      the control group with placebo, with a course of 3 months for both groups.
      Besides, 20 healthy subjects were selected as the normal group. The changes of
      memory ability were observed and the volume of hippocampus was detected by MRI
      before and after treatment. RESULTS: Memory quotient (MQ) was significantly lower
      in MCI patients than in healthy subjects (P < 0.01), after treatment it increased
      in the treated group as compared with that before treatment (P < 0.01), and the
      increment was higher than that in the control group (P < 0.05); the volume of
      hippocampus, total or that of either side, as well as the increment of the total
      volume of hippocampus in the treated group were all higher than those in the
      control group (P < 0.05). CONCLUSION: WYG could improve memory ability in MCI
      patients and could prevent and treat the hippocampal atrophy to certain degree.

PMID- 17205816
TI  - [Effect of electroacupuncture on bispectral index of electroencephalography in
      patients undergoing subtotal thyroidectomy].
AB  - OBJECTIVE: To investigate the effects of electroacupuncture on bispectral index
      (BIS) of electroencephalography in patients undergoing subtotal thyroidectomy.
      METHODS: Sixty patients were equally randomized into group A given
      electroacupuncture combined with cervical plexus block (CPB) and group B given
      CPB alone. After needling sensation was reached in bilateral "Hegu" and "Neiguan"
      acupoints, 5 min of high frequency electrical stimulation by electrical
      stimulation device followed with CPB was applied to group A, while only CPB was
      performed in group B. Visual analog scale (VAS) and verbal stress scale (VSS)
      were monitored, complication and adverse reaction were observed and BIS, mean
      arterial pressure (MAP), heart rate (HR) and arterial oxygen saturation (SaO2)
      were monitored continuously in the perioperative period. RESULTS: HR increased
      and BIS decreased in group A, both were lower significantly than those in group B
      (P < 0.01); MAP, the complementary dosage of fentanyl and lidocaine used and
      scores of VAS and VSS were also lower in group A than those in group B (P <
      0.01). CONCLUSION: Electroacupuncture could enhance the anesthetic effect of CPB,
      lower the BIS value during subtotal thyroidectomy.

PMID- 17205817
TI  - [Effect of three-step sequential method on Th1/Th2 in patients with
      corticosteroid-dependent asthma].
AB  - OBJECTIVE: To investigate the therapeutic mechanism of three-step sequential
      method (TSSM) on patients with corticosteroid-dependent asthma (SDA). METHODS:
      Forty patients with SDA were randomly assigned according to the randomizing
      number table to two groups equally, the treated group treated with three-step
      sequential recipes plus inhalation of Pulmicort Turbuhaler 200 microg, twice a
      day, and the control group treated with Pulmicort Turbuhaler alone. The
      therapeutic course for both groups was 12 - 14 weeks. Changes of the symptom
      score of asthma, the corticosteroid dosage used and the lung function were
      observed and the positive expression rate of IFN-gamma and IL-4 in peripheral
      CD4+ T cells were determined by flow cytometry before and after treatment.
      RESULTS: There was significant difference in the asthma symptom score, the oral
      corticosteroid dosage and the lung function between the treated group and the
      control group after treatment (P < 0.01). The expression rate of Th2 reduced, the
      ratio of Th1/Th2 increased significantly after treatment in both groups (P <
      0.01, P < 0.05), but the changes were more remarkable in the treated group than
      those in the control group, showing significant difference between them (P <
      0.01), while the expression rate of Th1 had no obvious change after treatment
      with no significant difference shown between the two groups (P > 0.05).
      CONCLUSION: TSSM can regulate imbalance of Th1/Th2, inhibit generation of
      inflammatory cytokines, decrease airway hyper-response, and therefore improve the
      pulmonary function, alleviate the asthmatic symptoms and reduce the patients'
      dependence on corticosteroid.

PMID- 17205818
TI  - [Effect of Chinese medicine for resolving dampness on activated and functional T
      lymphocyte subsets in chronic hepatitis B patients with dampness syndrome].
AB  - OBJECTIVE: To explore the relation between the effect of Huashi Decoction (HD)
      and levels of activated and functional T lymphocyte subsets in chronic hepatitis
      B (CHB) patients of dampness syndrome (DS). METHODS: Seventy CHB patients were
      nonrandomly assigned to two groups, the treated group (n = 45) treated by HD and
      the control group (n = 30) by nucleotide analogies. The clinical efficay was
      observed and levels of activated and functional T lymphocyte subsets were
      detected before and after treatment. RESULTS: The peripheral blood levels of CD8+
      CD28+ and CD4+ CD28+ T cells were significantly lower in CHB patients than those
      in the healthy subjects (P < 0.01), which were higher in the treated group after
      treatment compared with those before treatment (P < 0.05), while the CD8+ CD38+ T
      cell level was significantly higher in CHB patients than in the healthy subjects
      (P < 0.05), which was lower in the treated and the control groups after treatment
      than those before treatment respectively (P < 0.05). No significant difference
      was found in the markedly effective rate and total effective rate between the two
      groups (P > 0.05). The levels of CD8+ CD28+ and CD4+ CD28+ T cells increased and
      the CD8+ CD3+ and CD4+ CD25+ T cell level decreased obviously after treatment in
      those who acquired marked effectiveness (P < 0.05), while they changed
      insignificantly in those who did not acquire marked effectiveness (P > 0.05).
      CONCLUSION: HD is effective in regulating activated and functional T lymphocyte
      subsets in CHB patients with DS, which might be its mechanism of inhibiting virus
      replication and eliminating virus.

PMID- 17205819
TI  - [Preliminary study on differential expressed genes in T lymphocyte of chronic
      obstructive pulmonary disease patients with Fei-qi deficiency syndrome].
AB  - OBJECTIVE: To study T lymphocyte related genes with differential expression in
      patients with chronic obstructive pulmonary disease (COPD) of Fei-qi deficiency
      (FQD) syndrome type by gene chips. METHODS: Lymphocytes in peripheral blood were
      isolated by Ficoll technique from blood samples collected from COPD patients of
      FQD syndrome type, Fei-yin deficiency (FYD) syndrome type, and also from healthy
      subjects for control. They were sorted and purified by flow cytometry, and the
      different expressed genes were screened from them by gene chip technique.
      RESULTS: There were 15 genes with high differential expression between patients
      of FQD type and those of FYD syndrome type, and between patients of FQD type and
      healthy subjects. CONCLUSION: Gene chip technique could be used for studying the
      gene expression profiles of TCM syndrome, and the T-lymphocyte related genes with
      differential expression in COPD patients with FQD were screened preliminarily.

PMID- 17205820
TI  - [Correlation between TCM syndrome type and intracranial aggressive potentiality
      of untreated nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the correlation between TCM syndrome type and
      intracranial aggressive potentiality of untreated nasopharyngeal carcinoma (NPC).
      METHODS: Sixty untreated NPC patients of different syndrome types were treated
      conventionally and followed up for over one year. Correlation between the TCM
      syndrome type differentiated at the first consultation and the intracranial
      aggressive potentiality of the primary focus of NPC were analyzed. RESULTS: The
      incidence of intracranial aggression was significantly higher in patients with Qi
      Yin deficiency type than that in those with other two syndrome types during the
      follow-up period (P < 0.01). CONCLUSION: The intracranial aggessive rate in the
      untreated NPC patients of Qi-Yin deficiency type was higher than in those of
      either Qi and blood coagulation type or fire-toxin stagnation type.

PMID- 17205821
TI  - [Effects of resolving phlegm method on fibrinolytic status in non-alcoholic
      steatohepatitis patients of phlegm and blood-stasis syndrome].
AB  - OBJECTIVE: To observe the effect of resolving phlegm method (RPM) on fibrinolytic
      status in non-alcoholic steatohepatitis (NASH) patients of phlegm blood-stasis
      (PBS) syndrome type. METHODS: Sixty-two patients were randomly assigned to 2
      groups, namely the treated group (n = 34) treated with Chinese herbs for
      resolving phlegm and dampness, smoothing liver and gallbladder, promoting blood
      circulation and removing blood stasis (composition: Indigo Naturalis 10 g, Alumen
      3 g, Semen Cassiae 15 g, Fructus Crataegi 15 g, vinegar prepared Radix Bupleuri
      10 g, Radix Curcumae 10 g, Radix Salviae Miltiorrhizae 12 g, Herba Lycopi 12 g,
      talc 12 g and Radix Glycyrrhizae 2 g), one dose twice per day orally, and the
      control group (n = 28) with ursodeoxycholic acid tablet (UAT) 150 mg three times
      per day. The treatment course for both groups was 12 weeks. Liver function (ALT,
      AST, ALP), insulin resistance (IR) index represented by homeostasis model-IR
      (HOMA-IR) and insulin (Ins), levels of tissue plasminogen activator (t-PA) and
      plasminogen activator inhibitor-1 (PAI-1), as well as main symptoms and physical
      signs were assessed before and after treatment. RESULTS: (1) Compared with those
      before treatment, levels of ALT, AST, HOMA-IR, t-PA, PAl-1 and main symptoms were
      all improved in the treated group (P < 0.05 or P < 0.01); (2) There was
      significant difference in ALP, HOMA-IR, t-PA and PAI-1 between the treated group
      and the control group (P < 0.05 or P < 0.01); (3) The improvement in liver
      function related indexes in the control group was mainly the level of ALT, t-PA
      (P < 0.01), and also shown on HOMA-IR, Ins and PAI-1. CONCLUSION: RPM could
      effectively improve liver function and fibrinolytic status. Its effect was better
      than that of UAT.

PMID- 17205822
TI  - [Effects of multi-glycoside of Tripterygium wilfordii Hook. f. on proteinuria and
      expression of slit diaphragm-associated molecules in rats with anti-thy1.1
      glomerulonephritis].
AB  - OBJECTIVE: To examine the effect of multi-glycoside of Tripterygium wilfordii
      Hook. f. (GTW) on proteinuria and expression of slit diaphragm-associated
      molecules such as nephrin and podocin in glomerulonephritis induced by anti
      Thy1.1 antibody (anti-Thy1 . 1 GN). METHODS: Anti-Thy1.1 GN was induced in rats
      by a single intravenous injection with 500 microg of anti-Thy1.1 mAb 1-22-3.
      Fourteen rats were randomly divided into 2 groups, the GTW-treated group and
      vehicle treated group, and sacrificed on day 14 in Experiment 1 or on day 7 in
      Experiment 2 after induction of Anti-Thy1.1 GN. Daily oral administration of GTW
      and vehicle as a control was started from 3 days before injection or at the same
      time of injection to the day of sacrifice in Experiment 1 or 2. Proteinuria was
      determined during 14 days in Experiment 1 or during 7 days in Experiment 2. From
      kidneys taken at sacrifice, glomerular morphological changes, glomerular
      macrophage infiltration, glomerular expression of nephrin and podocin, and its
      mRNA expression in renal tissue were examined. RESULTS: In Experiment 1,
      proteinuria and mesangial matrix expansion were significantly attenuated by GTW
      treatment. No difference in staining intensity of nephrin and podocin in
      glomeruli was observed between GTW treated group and vehicle treated group on day
      14. In Experiment 2, GTW treatment significantly ameliorated proteinuria,
      mesangial injury and activated macrophage infiltration in glomerulus. In
      addition, it significantly increased the expression of nephrin and podocin and
      its mRNA expression in glomeruli on day 7. CONCLUSION: In anti-Thy1.1 GN, the
      reduced expression of nephrin and podocin may contribute to the development of
      mesangial injury and proteinuria. The findings suggest that GTW ameliorates not
      only proteinuria but also mesangial lesions in anti-Thy1 . 1 GN most likely by
      increasing the expression of nephrin and podocin.

PMID- 17205823
TI  - [Effect of puerarin on ADMA-DDAH system in human umbilical vein endothelial cells
      cultured with oxidized free radical].
AB  - OBJECTIVE: To observe the effects of puerarin on activity of dimethylarginine
      dimethylaminohydrolase (DDAH) in human umbilical vein endothelial cells (HUVECs)
      cultured with oxidized free radical (OFR), to explore the effect of puerarin on
      metabolic mechanism of asymmetric dimethylarginine (ADMA). METHODS: HUVECs of the
      3rd - 6th passage cultured with modified Jaffe's method were divided into 4
      groups, the blank control group cultured with DMEM medium, the OFR group cultured
      with DMEM medium containing 0.1 mmol of OFR per liter, the puerarin group 1 and 2
      cultured with DMEM medium containing 0.1 mmol of OFR per liter as well as 0.5
      mg/ml and 1.0 mg/ml of puerarin respectively. After being incubated for 24 h,
      activity of nitric oxide synthase (NOS), contents of nitric oxide (NO), ADMA,
      endothelin (ET), and L-citrulline (L-cit) in the supernate were measured, and
      DDAH protein expression in the lysate was detected by Western blotting. RESULTS:
      Compared with those in the blank control group, ADMA and ET contents were higher,
      while the levels of NO and L-cit and the activity of NOS were lower markedly, but
      the DDAH expression changed insignificantly in the OFR group. These abnormalities
      were restored significantly in the puerarin groups. CONCLUSION: The increase of
      ADMA in OFR injured HUVECs was correlated with the reduction of DDAH activity and
      irrelevant to DDAH expression. Puerarin could promote ADMA metabolism through
      increasing DDAH activity, and improve NOS activity, thus to reduce the impairing
      of OFR on endothelial function.

PMID- 17205824
TI  - [Regulatory effect of Wenyang Whengling Decoction on Smads expressions in testis
      of sterile rats with Shen-yang deficiency].
AB  - OBJECTIVE: To study the localization and distribution of expressions of Smads
      (mother against dpp), the intracellular signal transduction molecules in the
      transforming growth factor-beta (TGF-beta) family, in the testis of male sterile
      rats with Shen-yang deficiency induced by adenine and to observe the effect of
      Wenyang Shengjing Decoction (WSD) on these expressions. METHODS: Rats were
      randomly divided into the control group, the model group and the WSD group.
      Localization and distribution of Smad 1, Smad 2 and Smad 4 expressions were
      detected by immunohistochemistry SABC and semi-quantitative RT-PCR and analyzed
      statistically by image analysis system; the contents of testosterone (T),
      luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were detected by
      radioimmunoassay; and the weights of body, testis and epididymis, as well as
      sperm number of rats were also measured. RESULTS: Smad 1 and Smad 2 were
      expressed in cytoplasm of all levels of spermatogenic cells in rats' testis with
      their positive immuno-responsive substance locating in the cytoplasm, and
      positive Smad 2 expression could also be found in cytoplasm of Sertoli's cell,
      but both of them showed negative response in Leydig's cell; Smad 4 was positively
      expressed in cytoplasm of Leydig's cell but showed negative response in
      spermatogenic cell and Sertoli's cell. Compared with the normal control, Smad 1
      expression was lower (P < 0.05), but Smad 2 and Smad 4 were higher in the model
      group (both P < 0.05), these abnormal changes could be reversed by WSD treatment
      (all P < 0.05). Compared with the normal control group, the body weight, sperm
      number and serum T level were lower, and levels of FSH and LH were higher (all P
      < 0.05) in the model group, which could all be improved by WSD (P < 0.05); the
      weights of testis and epididymis were unchanged in all groups (P > 0.05).
      CONCLUSION: WSD could not only increase the sperm number through elevating serum
      T level and decreasing the levels of FSH and LH, but also by way of regulating
      Smads genes expression to adjust the levels of sex hormones, promote the
      production of sperm directly or indirectly, so as to treat male infertility.

PMID- 17205825
TI  - [Clinical observation on treatment of somatic disorder with combination of
      Xiaoyao Powder and Wendan Decoction].
AB  - OBJECTIVE: To compare the efficacy of Chinese medicine and selective serotonin
      reuptake inhibitors (SSRI), fluoxetine, on somatic disorder (SD) and to explore
      the advantage of Chinese medicine. METHODS: Patients with SD screened with
      Hamilton depression scale (HAMD) were randomly assigned to the fluoxetine group
      treated with fluoxetine 20 mg once per day administered after breakfast, and the
      Chinese medicine group with combination of Xiaoyao Decoction (XD) and Wendan
      Decoction (WD) one dose a day given before supper everyday, the treatment for
      both groups was lasted for 8 weeks. Clinical general impression (CGI) and symptom
      checklist 90 (SCL-90) were applied to evaluate the changes in symptoms before and
      after treatment, and a self-made rating scale was used to evaluate the adverse
      reaction. RESULTS: CGI score changed significantly in both groups after
      treatment, showed the average 2-week reduction rate of more than 30% and the
      average 8-week reduction rate of more than 70%, without significant difference
      shown between the two groups (P > 0.05). SCL-90 scoring showed the average score
      of somatic factor was significantly lower in the Chinese medicine group than in
      the fluoxetine group (P < 0.05) with few adverse reaction, while no significant
      difference was found in the respective scores of other factors between the two
      groups (P > 0.05). CONCLUSION: Chinese medicine shows noticeable superiority in
      treating SD, it has the effect similar to that of new antidepressants.

PMID- 17205826
TI  - [Toxicity attenuation and efficacy potentiation effect of liquorice on treatment
      of rheumatoid arthritis with Tripterygium wilfordii].
AB  - OBJECTIVE: To investigate the toxicity attenuation and efficacy potentiation
      effect of liquorice on treatment of rheumatoid arthritis (RA) with Tripterygium
      wilfordii (TW). METHODS: One hundred and twenty RA patients were randomly
      assigned to two groups: the treated group treated with compound decoctum of TW
      and liquorice and the control group with TW ployglycosidium tablets both based on
      routine treatment. The therapeutic effect and adverse reaction were observed
      after 2 months of treatment. RESULTS: The total efficacy rate was 89.8% in the
      treated group and 79.6% in the control group with insignificant difference
      between the two groups; the effect was better in the treated group than that of
      the control group in decreasing the swollen joint index and increasing the
      average grip strength of both hands (P < 0.05); the total incidence of adverse
      reaction was obviously lower in the treated group than that of the control (P <
      0.01). CONCLUSION: Liquorice has toxicity attenuation and efficacy potentiation
      effect on treatment of RA with TW.

PMID- 17205827
TI  - [Effect of Huangbai Liquid on expression of human beta-defensin-2 mRNA in skin
      lesions of patients with recurrent genital herpes].
AB  - OBJECTIVE: To investigate the expression of human beta-defensin-2 (HBD-2) mRNA in
      skin lesions of patients with recurrent genital herpes (RGH) and the effect of
      Huangbai Liquid (HL) on it. METHODS: Twenty-seven patients were randomly assigned
      to 2 groups, the HL group (n = 14) treated with HL and the famciclovir group (n =
      13) with famciclovir. HBD-2 expression of patients were detected before and after
      the treatment and compared with that of 10 healthy subjects. RESULTS: HBD-2
      expression was found in the skin lesions of both the healthy persons and the RGH
      patients before treatment. It is higher significantly in the HL group than in the
      famciclovir group after treatment. CONCLUSION: HL was suitable for treatment of
      RGH since it could improve immune function of RGH patients and keep a rather
      higher concentration of HBD-2 expression in local skin lesions.

PMID- 17205828
TI  - [An outstanding feature of traditional Chinese medicine: improving local
      pathology by regulating holistic function].
AB  - Holistic conception reflects that "Syndrome" summarizes all aspects and
      conditions related to occurrence of disease referring to different constitutions.
      "Treatment according to syndrome differentiation" improves local pathological
      changes through regulating holistic function, which is the practical application
      of holistic conception and an outstanding feature of TCM. According to syndrome
      differentiation, treatment shows favorable effects on local pathological changes
      as restenosis after coronary artery intervention therapy, excessive inflammation,
      vascular endothelial injury in coronary artery disease and hypoadrenocortical
      function with drugs for promoting blood to remove blood stasis, clearing heat and
      detoxifying toxin, and warming Shen-yang, and aromatic drugs for warming meridian
      to dredge obstruction.

PMID- 17205829
TI  - [Integral syndrome differentiation, local syndrome differentiation and
      microcosmic syndrome differentiation --thinking on the modern TCM system of
      syndrome differentiation dependent treatment].
AB  - From the historic and realistic viewpoints, the authors discussed the theory of
      TCM syndrome differentiation, pointing out that the modern TCM system of syndrome
      differentiation dependent treatment should consist of three components, the
      integral syndrome differentiation, local syndrome differentiation and microcosmic
      syndrome differentiation, they are independent comparatively and supplementary
      with each other.

PMID- 17205830
TI  - [Review of clinical and experimental studies on treatment of atherosclerosis with
      expelling phlegm and relieving blood stasis principle].
AB  - Atherosclerosis (AS) is one of the most essential factors to cause cardio
      cerebrovascular diseases. Abundant experience has been acquired in treatment of
      AS by traditional Chinese medicine (TCM) with its own distinctive diagnostic and
      therapeutic principles. To expell phlegm and relieve blood stasis, a hot topic of
      TCM therapeutic principle for AS, is reviewed in this paper.

PMID- 17205831
TI  - [Fundamental research on effect of Ginseng and its components on hematopoiesis
      and their clinical application].
AB  - Ginseng contains multiple components, such as saponins and saccharide, etc. The
      major is ginsenoside, which includes more than 40 kinds of monomers. It has been
      applied to treat blood-deficiency syndrome, but the action mechanism is still
      unclear. The fundamental researches on the effect of ginseng and its components
      on hematopoiesis and their clinical application were reviewed in this article.
      They were found to have effects on hematopoietic cells, microenvironment and
      regulatory factors, indicating they are potential for prevention of
      hemocytopenia, protection from injury of radiotherapy/chemotherapy and even for
      transplantation of hematopoietic stem cell.

PMID- 17205832
TI  - Dairy cow mortality. A review.
AB  - We reviewed the literature to give an overview over the mortality among dairy
      cows in countries with a relatively intensive dairy production. A total of 19
      studies focussing on dairy cow mortality were identified. Information about
      objectives, measures of mortality, sample sizes, study designs, causes of death
      and risk factors from these studies is presented and discussed. Additionally,
      recommendations for future recordings of mortality that will enable better
      possibilities for comparison of study results, generalization of results from a
      study population to a larger population and meta-analysis are given.

PMID- 17205833
TI  - Experimental studies on the impact of an increased dose of anionic salts on the
      metabolism of dairy cows.
AB  - This study was initiated to investigate the influence of a daily dose of anionic
      salts (AS) above the valid upper limit at present on metabolism of dairy cows.
      Eleven non-pregnant and non-lactating Holstein-Friesian crossbred cows with a
      permanent rumen cannula were used in a study with a controlled feeding design.
      The initial daily dose was 2500 meq/day, which resulted in a Dietary Cation Anion
      Difference (DCAD) of -211 meq/kg dry matter. Every seven days,the daily dose was
      raised by 500 meq. If a cow stopped eating, the application of AS was stopped and
      these cows were monitored over the next seven days. On day 30 another batch of
      hay, having the same DCAD but higher concentrations of minerals and energy, was
      fed. Blood and urine samples were taken to monitor acid-base balance and calcium
      concentrations. Acid-base balance was strongly influenced by AS. Blood pH dropped
      steadily and reached values around 7.23. Urine pH dropped quickly below 6 and
      remained at that level regardless of the increased dosage of AS. Net acid base
      excretion (NABE) fell continuously with the increase of the dosage of AS and
      reached values below -200 mmol/l. Calcium concentrations in the serum were nearly
      stable, but those in urine increased sharply and remained on an elevated level
      with increasing doses of AS. A few days before the individual cow's refusal of
      feed intake, calcium excretion in urine decreased. The majority of cows stopped
      eating while consuming a diet containing 3500 to 4000 meq AS except two animals
      who consumed up to 6000 meq/day AS but they received the better hay in the second
      half of the treatment period. In this time pH in blood increased slowly. NABE
      remained stable on a low level at -100 mmol/l. The results showed that with an
      increasing amount of AS fed the risk of clinical acidosis increased. The
      decreasing urine concentrations of calcium indicate a breakdown of the
      compensation capability of the single cow. Besides the dose of AS fed, the
      quality of the feed stuff might be another factor concerning the tolerance of
      cows against AS.

PMID- 17205834
TI  - Food safety surveillance through a risk based control programme: approach
      employed by the Belgian Federal Agency for the Safety of the Food Chain.
AB  - The principal responsibility of the Belgian Federal Agency for the Safety of the
      Food Chain (FASFC) is to guarantee the safety along the food chain. In order to
      accomplish this responsibility, the FASFC has developed an integrated official
      control program to check compliance with various regulations. The original
      methodology developed and applied by FASFC is presented. This methodology is
      based on risk evaluation, statistical tools and current scientific knowledge.

PMID- 17205835
TI  - Irish Nursing Homes Organisation's Nurses Committee.

PMID- 17205836
TI  - Selling a dental practice.

PMID- 17205837
TI  - EU Framework for Health Services.

PMID- 17205838
TI  - Bleaching.

PMID- 17205839
TI  - Amalgam issue.

PMID- 17205840
TI  - New Medical Practitioners Bill.

PMID- 17205841
TI  - Oral and dental aspects of Sjogren's syndrome.
AB  - Sjogren's syndrome is a common condition which can result in significant physical
      and emotional debility. Dentists can play a pivotal role in the prompt diagnosis,
      investigation and management of patients with Sjogren's syndrome. A sound
      understanding of the pathogenesis, presentation and current management of
      Sjogren's syndrome, will enable the general dental practitioner to make a
      significant contribution to the oral health and general well-being of those
      affected by the disease. This article aims to provide the general dental
      practitioner with a comprehensive and practical guide to current developments and
      best practise in the care of these individuals.

PMID- 17205842
TI  - Vocational training in Ireland: an overview.
AB  - Vocational training in dentistry in Ireland was first established in 1999 to
      introduce new graduates to the practice of dentistry and to provide general
      dental training. The Vocational Dental Practitioner (VDP) spends two days per
      week in private practice, two days in the health board and one day on day-release
      attending lectures. Their salary is paid by the Health Service Executive (HSE).
      The VDP completes a portfolio book throughout the year to demonstrate their
      progress. Vocational training is not currently mandatory in Ireland. However it
      does come highly recommended as an excellent start to any dental career.

PMID- 17205843
TI  - Avoiding perforations in endodontics.
AB  - PRECIS: While it will be impossible to eliminate all iatrogenic errors in
      endodontics, by focusing on key areas during the endodontic process, we can
      reduce the potential for problems for ourselves and our patients.

PMID- 17205844
TI  - An audit of the laboratory service provided to the Health Service Executive
      Orthodontic Department, St James Hospital, Dublin.
AB  - PURPOSE OF THE STUDY: To evaluate the service purchased from contracted
      orthodontic laboratories used by HSE (SWA) regional orthodontic unit, St. James's
      Hospital, Dublin and identify deficiencies in the current service. MATERIALS AND
      METHODS: A data collection questionnaire was designed and distributed to the
      departmental orthodontists for a period of three months (October-December 2004).
      Gold standards, drawn up based on the authors' ideal requirements and published
      guidelines, were supplied to grade the work returned. RESULTS: During the study
      period 363 items of laboratory work were requested. 20% of the laboratory work
      arrived late and most of the delayed work was delayed for more than 24 hours.
      Most laboratory delays occurred with functional appliances, retainers and study
      models. Prior to fit, 20% of the appliances required adjustments for more than 30
      seconds. 65% of laboratory work returned to the department met all of the gold
      standards. 10% of appliances were considered unsatisfactory. Functional
      appliances were most often ill fitting accounting for almost half of the
      unsatisfactory laboratory work. CONCLUSIONS: The majority of the laboratory work
      returned to the department met our gold standards and arrived on time. Forty six
      percent of the appliances required adjustments. Functional appliances required
      the most adjustments; one in five of all functional appliances ordered were
      considered unsatisfactory.

PMID- 17205845
TI  - Crash course in accounts.

PMID- 17205846
TI  - Sharing the burden.
AB  - Expense sharing arrangements are extremely beneficial to dentists and not just in
      a financial sense. They can be easy to organise and administer, but must be based
      on a proper written legal agreement.

PMID- 17205847
TI  - Promoting inclusive services.

PMID- 17205848
TI  - Bureaucracy and centralisation are destroying midwives' morale.

PMID- 17205849
TI  - Bridging the inequality gap.

PMID- 17205850
TI  - Professional ethics and charging for care.

PMID- 17205851
TI  - Learning form Isabella's story.

PMID- 17205852
TI  - Make sure they get a healthy start.

PMID- 17205853
TI  - Midwifery basics: women's health needs (3). Menstrual health.

PMID- 17205854
TI  - Mary's midwife: a Christmas legend.

PMID- 17205855
TI  - Mind the bully: using emotional intelligence.

PMID- 17205856
TI  - Vaginal birth after caesarean (part 3).

PMID- 17205857
TI  - The importance of small things.

PMID- 17205858
TI  - Benefit of electrocardiography during front-line combination paclitaxel and
      carboplatin chemotherapy for epithelial ovarian cancer.
AB  - OBJECTIVE: To evaluate the patterns of electrocardiography (ECG), cardiac risk
      factors and its clinical consequence in women with epithelial ovarian cancer
      (EOC) who received paclitaxel and carboplatin (PC) as front line chemotherapy.
      MATERIAL AND METHOD: The medical records and electrocardiographic data of women
      with EOC who received paclitaxel (175 mg/min2) and carboplatin (AUC=5) every 3
      weeks at Chiang Mai University Hospital between January 2000 and December 2004
      were reviewed for cardiac risk factors and clinical consequence. RESULTS: Among
      79 women receiving PC for EOC, 43 (54.4%) had cardiac risk factors. Seventy
      (88.6%) women had normal ECG, the remaining nine had sinus tachycardia (5),
      bundle branch block (2), mild T inversion (1), and Wolff-Parkinson-White syndrome
      (1) before the first course of chemotherapy. Among 70 women with normal initial
      ECG 8 (11.4%) had sinus tachycardia, one (1.4%) had early depolarization, two
      (2.9%) had sinus bradycardia and three (4.3%) had sinus arrhythmia in subsequent
      ECG All these cardiac disturbances were asymptomatic and needed no intervention,
      indicating grade I toxicity. The odds ratio of developing abnormal ECG in women
      with cardiac risk factor was 1.24 (95% CI = 0.33 to 4.64, p = 0.77). Among nine
      patients with abnormal ECG before the first course of PC, six (66.7%) had
      subsequent abnormal ECG but all were asymptomatic and no worsening of abnormal
      ECG pattern was noted. CONCLUSION: Although paclitaxel and carboplatin
      chemotherapy could induce abnormal ECG in women with either normal or abnormal
      prior ECG, its consequence was of no clinical significance. Therefore, the
      benefit of ECG before each treatment course was theoretically limited.

PMID- 17205859
TI  - Cytomorphologic comparison between rehydrated air-dried and conventional wet
      fixed pap smears.
AB  - OBJECTIVE: To compare the cytomorphologic quality of the cervical (Pap) smears
      between two fixation techniques, rehydration of air-dried smears (AD) versus wet
      fixation (WF). MATERIAL AND METHOD: Paired-cervical smears (AD and WF) from 172
      women who underwent cervical cytology screening at Chiang Mai University Hospital
      between August 2004 and September 2004 were prospectively evaluated for the
      cytologic parameters and the staining qualities. RESULTS: The mean age of the 172
      women was 41.7 years +/-2 SD 18.1), 27 women (15.7%) were postmenopausal. Absence
      ofred blood cells in the smear background was significantly more frequent in AD
      smears than in WF specimens (p = 0.0006). Air-drying artifact was more frequent
      in AD smears compared to those of WF (p = 0.036) but was of only mild degree in
      all cases. There was no significant difference between AD and WF smears in the
      cytoplasmic quality including distinctness of cell border (p = 0.30) and
      satisfactory staining (p = 0.054). For the nuclear morphology, there was no
      significant difference between both fixation techniques in the distinctness of
      nuclear border (p = 0.26) and chromatin crispness (p = 0.23) of the endocervical
      nuclei. In squamous nuclei, AD smears had higher frequency of indistinct nuclear
      border and hazy chromatin compared to WF smears (p = 0.003 each). However, these
      were observed in only mild degree and did not affect the cytologic
      interpretation. CONCLUSION: The quality of AD smears was slightly inferior to WF
      smears but was still satisfactory for cervical cytology. AD technique may be
      acceptable as an alternative to wet fixation in cytologic cervical cancer
      screening.

PMID- 17205860
TI  - Obstetric hysterectomy: a 14-year experience of Rajavithi Hospital 1989-2002.
AB  - OBJECTIVES: To review and compare the incidence rate of obstetric hysterectomised
      patients between two seven-year periods. Theperiods were from October 1, 1988 to
      September 30, 1995 andfrom October P', 1995 to September 30th, 2002. The data
      included demographic characteristics, indications, possible risk factors,
      complications, and operative managements. MATERIAL AND METHOD: Retrospective
      analysis of the data that was collected from medical and labor records of the
      obstetric hysterectomised patientsfrom October 1, 1995 to September 30, 2002, the
      second seven-year period, compared with those in Pratumthong and
      Wattanaruangkowit's study from October 1, 1988 to September 30, 1995, the first
      seven-year period. RESULTS: Between 1998 and 2002, there were 201, 696 total
      deliveries with 111 obstetric hysterectomies. A significant increase in the
      average incidence rate of hysterectomy from 0.42 to 0.76/1000 deliveries and
      maternal age, placenta previa and blood transfusion in the second period compared
      with the first period (p < 0.05). Postoperative complications and the other risk
      factors of obstetric hysterectomy were not significant difference. CONCLUSION:
      The present study of obstetric hysterectomy demonstrates a significant increase
      in the incidence of hysterectomised rate, maternal age, blood transfusion, and
      placenta previa in the second period compared with the first period.

PMID- 17205861
TI  - Use of Hachinski Ischemic Score in the memory clinic: Thai experience.
AB  - BACKGROUND: The validity ofHachinski Ischemic Score (HIS) in differentiating
      between Alzheimer's disease (AD) and Vascular dementia (VaD) has been questioned
      and compared with the gold standard autopsy. OBJECTIVE: To confirm that the HIS
      can be used to differentiate related VaD from AD in a Thai population. MATERIAL
      AND METHOD: A prospective study of 398 patients who were attending the Memory
      Clinic, at Siriraj Hospital between January 2001 and October 2003. RESULTS: The
      214 patients, with a mean age of 71.15 + 10.20 years, were classified as AD, VaD
      or mixed dementia (AD with cerebrovascular disease) in proportion of 60.2%,
      30.4%, and 9.3% respectively. The authors propose HIS at 5 as a cut off point to
      differentiate patients with AD and those with VaD or AD with cerebrovascular
      disease with sensitivity of 85.3% and specificity of 72.9%. CONCLUSION: The HIS
      can be applied to differentiate dementia related vascular etiology from AD in a
      Thai population.

PMID- 17205862
TI  - Patterns of single photon emission tomography (SPECT) among patients with
      dementia in the memory clinic at Siriraj Hospital.
AB  - OBJECTIVE: The authors hypothesized that there is a pattern difference in
      cerebralperfusion of the 99-Technitium L, L-ethyl cysteinate dimer Single Photon
      Emission Computer Tomography (99-Tc ECD SPECT) between mild and moderate to
      severe dementia. MATERIAL AND METHOD: The authors reported a retrospective study
      in the Memory Clinic, Siriraj Hospital between January 2001 and October 2003
      including only patients with Alzheimer's disease, vascular dementia, and mixed
      dementia. Clinical dementia rating (CDR) was used to document dementia severity.
      Patterns of hypoperfusion were classified into no definite hypoperfusion,
      regional hypoperfusion, and diffused hypoperfusion. RESULTS: One hundred and
      seven patients were included in the present study. Only mean Thai Mental State
      Examination (TMSE) score was different between the two groups. There was no
      significant correlation between pattern of hypoperfusion in brain SPECT and
      severity of dementia. CONCLUSION: The authors cannot demonstrate the pattern of
      hypoperfusion of 99-Tc ECD SPECT among patients' difference in dementia severity.

PMID- 17205863
TI  - Rural-urban difference in lipid levels and prevalence of dyslipidemia: a
      population-based study in Khon Kaen province, Thailand.
AB  - OBJECTIVES: To determine the lipid levels and examine the effect of an urban
      lifestyle on dyslipidemia, by comparing the lipid levels and the prevalence of
      dyslipidemia of rural vs. urban dwellers in Thailand MATERIAL AND METHOD: A cross
      sectional study was conducted in both rural and urban areas of Khon Kaen
      province. After a 12-hour fast, blood was drawn for assessment of total
      cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C) and low
      density lipoprotein (LDL-C) cholesterol. The classification of dyslipidemia was
      based on the NCEP A TP III guidelines. RESULTS: The authors recruited 916
      subjects (595 urban; 321 rural), ranging between 20 and 88 years of age. In both
      the men and women, the mean TC and LDL-C were significantly higher in urban vs.
      rural subjects (TC; 207 vs. 169 for men and 204 vs. 192 mg/dl for women and LDL
      C; 120 vs. 87 for men and 122 vs. 110 mg/dl for women, p < 0.001). The rural
      women had a significantly higher mean TG (159 vs. 111 mg/dl, p < 0.001) but lower
      HDL-C (51 vs. 59, mg/dl, p < 0.001) than urban women. The TG and HDL-C between
      urban and rural men was not significantly different. Urban men had a
      significantly higher prevalence of dyslipidemia (TC > or =240 and LDL-C > or = 60
      mg/dl) than rural men (25.9 vs. .3.7 per cent for TC and 16.7 vs. 3.7 percent for
      LDL-C, p < 0.001) while the prevalence of hypertriglyceridemia (> or =200 mg/dl)
      and low HDL-C (< 40 mg/dl) was significantly higher in rural women (18.2 vs. 7.9
      percent for TG and 15.0 vs. 3.8 per cent of HDL-C, p < 0.001). The results were
      unchanged after matching for age and sex between the urban and rural populations.
      CONCLUSION: This present study demonstrated a significant difference in urban vs.
      rural lipid levels and the prevalence of dyslipidemia. Migration to urban centers
      and adopting an urban lifestyle is likely related to the rising lipid level and
      prevalence of dyslipidemia.

PMID- 17205864
TI  - Role of drowsy driving in traffic accidents: a questionnaire survey of Thai
      commercial bus/truck drivers.
AB  - OBJECTIVE: The authors assessed the relationship between traffic accidents and
      drowsiness. MATERIAL AND METHOD: A self-answered questionnaire survey of 4331
      commercial bus/truck drivers was done. RESULT: Sixty-nine percent of the drivers
      reported accidents and one third of these accidents was attributable to
      drowsiness. Drowsy driving and microsleeps were experienced by 75% and 28% of
      drivers respectively. Forty-five percent of drivers had excessive daytime
      sleepiness based on the Epworth Sleepiness Scale (ESS score > or =11). This
      excessive daytime sleepiness was strongly associated with feeling drowsy,
      microsleeps, and accidents. The major causes of drowsiness were sleep deprivation
      (90%), medications that caused sleepiness (78%), drinking alcohol the previous
      night (23%), and chronic loud snoring with or without obesity (17%). 61% of
      drivers worked longer than 12 hours with no days off The feeling of drowsiness at
      the wheel was also closely related to long hours of driving (>4 hours).
      Countermeasures that drivers used to keep them awake were talking to someone,
      drinking coffee or caffeinated-energy drinks, chewing snacks or gum and pulling
      over to have a nap. CONCLUSION: There is a strong relationship between accidents
      and drowsiness in commercial bus/truck drivers. The main cause of drowsiness was
      sleep deprivation. The authors hope that this information will help the public
      authority develop a policy to reduce the traffic accidents attributable to drowsy
      driving in commercial bus/truck drivers.

PMID- 17205865
TI  - Galactomannan antigenemia for the diagnosis of invasive aspergillosis in
      neutropenic patients with hematological disorders.
AB  - OBJECTIVES: Invasive aspergillosis (IA) is among the most common invasive fungal
      infections in neutropenic patients with hematological disorders in the authors'
      institution, King Chulalongkorn Memorial Hospital (KCMH), Bangkok, Thailand
      Previous studies have reported the Aspergillus galactomannan enzyme immunosorbent
      assay (GMEIA) may be a useful diagnostic tool for IA. The authors evaluated the
      performance of the GM EIA for the diagnosis and monitoring of the course of IA in
      KCMH. MATERIAL AND METHOD: The authors prospectively performed the study from
      June 2002 to January 2004 in a consecutive series of adult neutropenic patients
      with hematological disorders who were at risk for developing IA. During
      hospitalization, serum galactomannan levels were measured once or twice weekly
      using the Platellia Aspergillus EIA test kit. The sensitivity and specificity of
      the GM EIA were calculated according to the proportion of patients with true and
      false positive and negative tests. RESULTS: There were 50 treatment episodes in
      44 patients with 5 proven, 12 probable, and 33 possible or no IA. The cutoff GM
      index of > 0.75 was determined with a sensitivity of 94.1% and a specificity of
      78.8%. There was a close relationship between clinical outcome and the kinetics
      of GM indices. CONCLUSION: The GM EIA is a useful diagnostic toolfor the
      diagnosis and monitoring of the course oflA in the presented institute.

PMID- 17205866
TI  - Survival time of AIDS patients in Bamrasnaradura Institute.
AB  - A retrospective cohort study compared the survival time of AIDS patients, or HIV
      infected patients who had a CD4 count less than 200 cell/mm3, who had Thailands
      local triple anti-retroviral drugs regimen (GPO-VIR) with original triple anti
      retroviral therapy without protease inhibitor in Bamrasnaradura Institute. The
      result proved that survival time in patients who had local anti-retroviral drugs
      was the same as patients who had original triple anti-retroviral therapy without
      protease inhibitor (log rank p-value = 0.9617). In conclusion, local anti
      retroviral drugs can be used to prolong patients' survival time as much as
      original triple anti-retroviral therapy without protease inhibitor

PMID- 17205867
TI  - Breast pain and service satisfaction during digital mammography.
AB  - OBJECTIVES: To determine the frequency and predisposing factors of breast pain
      felt during digital mammography, and factors associated with service
      satisfaction. MATERIAL AND METHOD: A questionnaire was distributed to 1250 women
      immediately after their mammography. The outcomes assessed were a five-point
      scale of breast pain and rating of the satisfaction with the mammography service.
      Several factors potentially associated with breast pain and satisfaction were
      obtained from the questionnaire and analyzed. Multiple cumulative logit
      regression was used to identify independent, significant factors. RESULTS: Breast
      pain was found to be absent in 22% of patients, slight in 50%, moderate in 23%
      and substantial or severe in only 4%. Significant factors associated with breast
      pain during mammography included higher educational level, having no children,
      having had prior mammography, impolite and rough radiographer and poorly
      performed mammography. Factors associated with satisfaction with the mammography
      service included older age, polite and gentle radiographer and well-performed
      mammography. CONCLUSION: Radiographer delivery of the mammography service seemed
      to be the most important, modifiable reason for breast pain during mammography
      and dissatisfaction with the mammography service.

PMID- 17205868
TI  - Preoperative capecitabine with pelvic radiotherapy for locally advanced rectal
      cancer (phase I trial).
AB  - OBJECTIVE: Phase I multicenter study defined the maximal tolerated dose (MTD),
      dose-limiting toxicity (DLT) and safety profile of capecitabine in combination
      with preoperative radiation for patients with locally advanced rectal cancer
      (LARC). MATERIAL AND METHOD: Patients were treated with oral capecitabine (700,
      800, 900, 1000, 1100 and 1200 mg/m2 twice daily continuously) plus preoperative
      whole pelvic irradiation (45-46 Gy in 23-25 fractions over 5-6 weeks). Surgery
      was performed at the median of 42 days after chemoradiation treatment. RESULTS:
      Twenty-seven patients were in this trial. Eighteen patients (3 per dose level)
      had received capecitabine from 700 mg/m2 twice daily to the highest dose level of
      1200 mg/m2 twice daily. There were no grade 3/4 DLTs during dose escalation, a
      further nine patients were included at the highest capecitabine dose. Two of the
      twelve patients (16%) receiving capecitabine 1200 mg/m2 twice daily developed
      grade 3 diarrhea and discontinued treatment. There were no other grade 3/4
      adverse events. After capecitabine chemoradiation, 24 of 27 patients (89%)
      received definite surgery. Primary and lymph node down staging occurred in ten
      patients (42%). Sphincter-sparing surgery was performed in seven patients (26%)
      and abdominal-perineal resection was performed in 17 patients (63%). CONCLUSION:
      Preoperative capecitabine chemoradiation based on continuous daily capecitabine
      is very well tolerated in patients with LARC. The authors did not reach the MTD
      in the present study.

PMID- 17205869
TI  - 5-fluorouracil and mitomycin-C: effective, low-cost chemotherapy for colorectal
      cancer.
AB  - OBJECTIVE: To evaluate the regimen of 5-fluorouracil (5-FU) and mitomycin-C (MMC)
      in terms ofresponse rate and overall survival in advanced colorectal cancer.
      MATERIAL AND METHOD: Between January 1993 and December 2000, 121 from 559
      patients with advanced colorectal cancer were treated with chemotherapy. Bolus
      MMC (10 mg/m2) on first day, 5-FU (600 mg/m2/day) was given as a continuous
      infusion for 5 days, repeated every 4 weeks for 6 cycles. Toxicity and response
      were analyzed according to WHO criteria, and survival was analyzed according to
      Kaplan-Meier methodology. RESULTS: In the chemotherapy group (121 patients), 70
      were males and 51 were females, the mean age was 52 years. The ratio of colon and
      rectal cancer was 0.57. Nearly all patients (88.89%) had tumors with moderate
      differentiation. Forty patients with liver metastasis showed an overall response
      rate of 45% (95% CI 35.4-54.6) with a CR in 3 (7.5%) and PR in 15 (37.5%). The
      median survival was 13.1 months. The regimen was well tolerated with 11.64% of
      patients experiencing WHO grade 3-4 toxicity. CONCLUSION: The present study has
      indicated a highly active, acceptable toxic, inexpensive regimen of old drugs to
      be used as an alternative to the more expensive combination including CPT-11 or
      oxaliplatin.

PMID- 17205870
TI  - Palliative surgical bypass versus percutaneous transhepatic biliary drainage on
      unresectable hilar cholangiocarcinoma.
AB  - OBJECTIVE: To compare the survival probability of unresectable hilar
      cholangiocarcinoma patients who have been managed by palliative surgical bypass
      versus percutaneous transhepatic biliary drainage (PTBD). MATERIAL AND METHOD: A
      historical (retrospective) cohort study was performed by retrospective and
      prospective data collection. From January 1, 2000 to December 31, 2002, all
      unresectable hilar cholangiocarcinoma patients who received only one type of
      palliative surgical bypass or PTBD in Srinagarind Hospital, Khon Kaen University
      were included in the present study. The patients were followed until December 31,
      2004. Survival analysis was completed for all of the patients. STATISTIC
      ANALYSIS: Survival analysis was analyzed with the Kaplan-Meier method, Cox
      regression analysis, and Log-rank test. A p-value of less than 0.05 was
      considered significant. RESULTS: During the study period, 83 patients were
      included. Palliative surgical bypass was performed in 42 patients and PTBD was
      performed in 41 patients. Demographic data, peri-operative complication rate, and
      late complication rate were comparable. The median survival time of the
      palliative surgical bypass group was 160 days,(95% CI: 85.33, 234.67) and 82 days
      (95% CI: 29.76, 134.24)for PTBD group. Comparing survival experience by Log-rank
      test gave statistical significant diference (p = 0.0276). Hazard ratio was 0.599
      (p = 0.03) CONCLUSION: Survival rate of the palliative surgical bypass group was
      higher than the PTBD group. The survival rate of both groups was comparable to
      previous reports.

PMID- 17205871
TI  - Mechanical evaluation of aluminum alloy ring fixator.
AB  - OBJECTIVE: To test the homemade ring fixator as a tool for correction of bony
      deformity. MATERIAL AND METHOD: The authors developed an aluminum alloy ring
      fixator and tested it to find out the accuracy of manufacturing and strength of
      the ring systems under axial load with the Roundness Testing Machine and Lloyd
      Universal Testing Machine. RESULTS: The mean diameter of the twenty five-drill
      holes was 6.5843872 +/- 0.0521594 mm (mean +/- SD). Distance between particular
      drill holes, which reflected the precision of drilling, had a high accuracy with
      standard deviation from 0.1138 to 0.1870 mm. The roundness of the rings was
      0.2421376 +/- 0.12437977 mm (mean +/- SD). The system structure had minimal
      permanent deformity at breaking point, mean yield strength of the system was
      4786.9 +/- 14.353 N (mean +/- SD). This was caused by the failure of the wire.
      Mean stiffness of the system was 127 N./mm. CONCLUSION: The aluminum alloy ring
      fixator was strong enough and well tolerated for clinical usage

PMID- 17205872
TI  - Associations between floor activities and knee osteoarthritis in Thai Buddhist
      monks: the Songkhla study.
AB  - OBJECTIVE: Whether floor activity, a common daily activity among Buddhist monks,
      is a risk factor for knee osteoarthritis remains controversial. The objective of
      the present study was to search for any association between floor activities and
      knee osteoarthritis. MATERIAL AND METHOD: This population-based survey involved
      261 monks, 40 years of age or older from Songkhla province in the southern part
      of Thailand Histories were taken on lifetime floor activities in four common
      positions, squatting, lotus, side-knee bending, and kneeling. Radiographic
      investigations included antero-posterior and skyline views of both knees.
      Diagnosis of osteoarthritis in each compartment was based on Kellgren & Lawrence
      grade 2 or more. Logistic regression analysis adjusted for age, body mass index
      and smoking status was used to identify the associations between lifetime floor
      activity and knee osteoarthritis. RESULTS: The mean age (SD) of monks in the
      present study was 60.4 (12.7) with mean age at ordination 44.4 (17.6) years. The
      lotus and side-knee bending positions were the two most common practices. Using
      the lowest tertile of exposure to lotus position as a reference, the third
      tertile had an odds ratio of 1.0 (95% CI; 0.5-2.2) associated with radiographic
      knee osteoarthritis. The corresponding odds ratio for side-knee bending was 0.8
      (95% CI; 0.3-1.7), for squatting 2.1 (95% CI; 0.9-4.5), and for kneeling 0.7 (95%
      CI; 0.3-1.5). There was no significant association between the average daily
      lifetime floor activity in any positions and symptomatic radiographic knee
      osteoarthritis. CONCLUSION: Floor activities involving squatting, lotus, side
      knee bending and kneeling do not increase the risk of knee osteoarthritis in Thai
      Buddhist monks.

PMID- 17205873
TI  - Result of video-education on "genetic transmission in thalassemia" to thalassemic
      patients and their parents.
AB  - OBJECTIVE: To determine the degree of knowledge improvement and retention after a
      single viewing of a video CD presentation on the genetic transmission of
      thalassemia among patients with thalassemia and their parents. MATERIAL AND
      METHOD: The present research was approved by Khon Kaen University Ethics Review
      Board A video CD on the genetic transmission of thalassemia was created as an
      educational tool for improving knowledge and retention. The validity and the
      informative usefulness of the video CD was evaluated, adapted and approved by a
      thalassemia expert. Between November 1, 2002 and September 30, 2005, 61 subjects
      (thalassemic patients and their parents, both groups were in reproductively
      active ages) at the Pediatric Outpatient Unit, Srinagarind Hospital, Khon Kaen,
      consented to participate. Their ages ranged between 17 and 50 years (mean +/-SD =
      36.5 +/- 9.4; median = 38.0) and 44.3% completed elementary while 26.2% completed
      secondary school. Their occupations varied. Mothers, fathers, and thalassemic
      patients comprised 68.9%, 21.3%, and 9.8% of participants, respectively. In a
      quiet room in the Unit, each subject watched a single viewing of the video. A
      validated questionnaire (Cronbach's alpha coefficient = 0.79) with 40 true/false
      items was used to evaluate baseline knowledge on the genetic transmission of
      thalassemia. Knowledge was retested four times: immediately after the viewing,
      then at the 4th, 12th, and 24th week. The scores for each test were skewed toward
      high scores; therefore, non-parametric tests were used for the statistical
      evaluation. RESULTS: The running time for the video CD was 20 minutes. The
      baseline knowledge on genetic transmission was high. Immediately after a single
      viewing of the video, the knowledge level increased significantly (p = 0.000, 95%
      CI = 4.0-7.0) and was maintained up to the 12th week, after which (at the 24'h
      week) there was a significant drop (p = 0.020, 95% CI = -2.0 to 0) compared to
      the immediate post-test. CONCLUSION: The authors' video CD presentation
      effectively provided knowledge on the genetic transmission of thalassemia to
      patients with thalassemia and their parents. Post-viewing knowledge increased
      significantly and was retained for at least 12 weeks. Thereafter a refresher
      should be taken.

PMID- 17205874
TI  - Efficacy and safety of tacrolimus ointment in pediatric Patients with moderate to
      severe atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is an immunological skin disease. It is common
      in pediatric populations and often requires topical steroid treatment. Moderate
      to severe AD may not respond to topical steroids. They often require systemic
      steroids, which may result in growth retardation. Protopic, a non-steroid,
      tacrolimus based ointment which is a calcinurin inhibitor has been proved to be
      effective in caucacian with AD. OBJECTIVE: To evaluate safety and efficacy of
      0.03% tacrolimus ointment (Protopic&) in moderate to severe AD in pediatric
      patients age 2-12 years. MATERIAL AND METHOD: This was a one month multicenter
      open-label clinical trial using tacrolimus ointment twice daily in 61 subjects
      with moderate to severe AD from September to December 2004. Efficacy assessments
      were measured by Physician's Global Evaluation of Clinical Response (PhGECR),
      Eczema area and Severity Index (EASI), Patient's Global Evaluation of Clinical
      Response (PaGECR), and Quality of Life (QOL). Safety assessment was measured by
      incidence rate of adverse events. RESULTS: Fifty-eight patients completed the
      studies. Twenty-two patients were male; thirty-nine patients were female. Twenty
      nine patients had moderate AD. Thirty-two patients had severe AD. Three cases had
      discontinued treatment at the third week due to increase in severity. Over all
      PhGECR were significantly increased, 94% showed moderate improvement in PhGECR at
      week 4 or end of treatment (EOT)and 83% had better improvement in PaGECR at EOT
      Within 7 days, tacrolimus demonstrated rapid onset in reduction of EASI score and
      itch in patients. Mean QOL were significantly decreased at the end of the present
      study. Incidence of adverse events included application site burning (21%),
      itching (17%), pruritus (9%), infections(3%), and erythema and folliculitis (2%).
      Burning sensation, erythema, pruritus and itching were resolved after the first
      week. CONCLUSION: Topical tacrolimus ointment is effective and safe in moderate
      to severe AD. It significantly improved PhGECR, EASI, PaGECR, and QOL in
      pediatric patients after the first week of treatment and continued through the
      end of the study. The major adverse events were burning, itching, and pruritus,
      which were resolved within the first week of therapy.

PMID- 17205875
TI  - Auditory performance of cochlear implant children aged 2-5 years.
AB  - OBJECTIVE: To assess the categories of auditory performance in prelingual deaf
      children after implantation. STUDY DESIGN: Prospective study MATERIAL AND METHOD:
      The present study consisted of one boy and four girls aged between 2 and 5 years
      old at the time of implantation. All subjects had bilateral profound
      sensorineural hearing loss and received no substantial benefit from
      amplification. Three subjects were implanted with Med-El combi 40+ with CIS
      strategy and two subjects received multichanal monopolar Nucleus 24 cochlear
      implant with ACE strategy. After implantation, all subjects undertook a program
      ofhabilitation at the Speech and Hearing Clinic Ramathibodi Hospital. The
      Categories of Auditory Performance (CAP) score was determined at regular
      intervals prior to implantation, immediately at the initial mapping (0) and 3, 6,
      12 and 18 months after the implantation. RESULTS: The results showed that before
      implantation, only three children showed awareness of environment sounds, CAP
      score level 1, and that immediately after mapping, all of the children
      demonstrated awareness of the environmental sounds. Moreover, two of these
      children showed awareness of speech sounds, CAP score level 2. The CAP scores
      were gradually increased over a 12-month period. At the 12-month assessment
      interval, four children could discriminate two speech sounds, CAP score level 4
      and one child understood phrases without lip reading, CAP score level 5. 18
      months after of implantation, the CAP score for four children increased to level
      5. One child understood conversation without lip reading with a familiar talker,
      CAP score level 6. Furthermore, children with congenital hearing loss who
      underwent implantation at a younger age received more benefit from the
      implantation. CONCLUSION: The CAP score was found to be a useful and sensitive
      tool to evaluate the outcome of auditory receptive abilities in young congenital
      deaf children who underwent cochlear implantation. The accessible outcome
      measurement will provide information for parents and professionals to obtain a
      hierarchical scale on which the children's auditory ability with other more
      formal measures may be inappropriate.

PMID- 17205876
TI  - Prevalence of intestinal parasitic infections among school children in the
      central region of Thailand.
AB  - OBJECTIVE: Survey the prevalence of intestinal parasitic infections in 14 primary
      schools of Central Thailand. MATERIAL AND METHOD: A cross sectional survey of the
      prevalence of intestinal parasitic infections in 14 primary schools of Central
      Thailand that included Ang Thong, Ayudthaya, and Suphanburi provinces was
      conducted One thousand and thirty seven children with age ranging from 3-12 years
      (540 males and 497 females) were examined for intestinal parasites by the
      formalin-ether concentration technique. RESULT: The overall prevalence was 4.24%.
      The pathogenic parasites found were Giardia lamblia (1.25%), Enterobius
      vermicularis (0.19%), Trichuris trichiura and Hookworm (0.19% each),
      respectively. The common non-pathogenic protozoa found were Entamoeba coli
      (1.64%) and Endolimax nana (0.48%). The infection rate of Blastocystis hominis
      was 0.19%. CONCLUSION: Interestingly, the area studied which is low and flat and
      contains rice and water chestnut fields and small rivers, did not demonstrate
      Fasciolopsis buski as highly found in the past five decades. However, Parasittic
      infections are still public health problems in Thailand Close monitoring and
      control of parasitic infections is needed

PMID- 17205877
TI  - Single dose of 1% tropicamide and 10% phenylephrine for pupil dilation.
AB  - OBJECTIVE: To compare the efficacy of pupil dilation between a single dose and
      three doses of 1% tropicamide and 10% phenylephrine for binocular indirect
      ophthalmoscopy. MATERIAL AND METHOD: A prospective randomized double-blind
      clinical controlled trial was conducted. All patients underwent the binocular
      indirect ophthalmoscopy and met the inclusion criteria were randomized into two
      groups using block randomization. Group A received a single dose of 1%
      tropicamide and 10% phenylephrine eye drops, and Group B received three doses of
      the same drugs. The primary outcome was the horizontal pupil diameter measured by
      slit-lamp biomicroscope (Haag-Streit model 900) before and at 10, 15, 20, 25 and
      30 minutes after eye drop instillation. The clinical equivalence of the efficacy
      of pupil dilation between the two groups was defined as the difference of less
      than or equal to 1 mm (-1 mm to + 1 mm). RESULTS: Eighty patients (160 eyes) were
      randomized into 40 patients (80 eyes) in group A and 40 patients (80 eyes) in
      group B. The mean pupil sizes at baseline of group A were 3.51 +/- 0.63 mm in the
      right eye and 3.39 +/- 0.67 mm in the left eye. Those in group B were 3.61 +/-
      0.67 mm in the right eye and 3.66 +/- 0.72 mm in the left eye. The mean pupil
      diameters at 30 minutes of group A were 7.34 +/- 0.51 mm in the right eye and
      7.41 +/- 0.56 mm in the left eye, whereas those of group B were 7.49 +/- 0.45 mm
      in the right eye and 7.51 +/- 0.40 mm in the left eye. The mean difference of the
      pupil size between the two groups was 0.15 mm (p = 0.175) in the right eye and
      0.l0 mm (p = 0.362) in the left eye. The 95% confidence intervals of the
      difference in pupil size were -0.36 to 0.07 mm in the right eye and -0.32 to 0.12
      mm in the left eye. CONCLUSION: The 95% confidence interval of the difference in
      pupil size lay entirely within the range of equivalence. The single dose of 1%
      tropicamide and 10% phenylephrine was clinically equivalent to the three doses of
      the same drugs.

PMID- 17205878
TI  - Relationship between bone and ash weight to age, body weight and body length of
      thai adults after cremation.
AB  - BACKGROUND: Cremation is the most common Thai funeral mode. In Thailand, there
      have not been any previous reports of bone and ash weight after cremation.
      OBJECTIVE: Collect the bone and ash weight after the cremation and find the
      variables that affected the bone and ash weight. MATERIAL AND METHOD: One hundred
      and ten samples, including fifty-five males and fifty-five females, were
      collected from the Thai population. A Thai crematorium (Series Tiger 1) that
      could produce a temperature of approximately 850 degrees C - 1200 degrees C was
      employed. It took about 1-1.5 hours to complete the incineration. RESULTS: The
      average bone and ash weight of the males was 2.68 kg with SD 1.41; female was
      2.12 with SD 1.25; and total was 2.40 with SD 1.36. The present study supported
      that age and body weight affected the bone and ash weight while the body length
      (height) did not. The fitted equation was y = 1.969 - 0.01846 (age) + 0.03087
      (body weight), where y = predicted bone and ash weight. CONCLUSION: The present
      study shows that age and body weight affected the bone and ash weight. From this
      information, the authors could find the predicted value of either age or body
      weight. If the authors would like to find the age, the authors can employ the
      fittest equation y = 76.097 - 3.219 (Bone and ash weight) where y = predicted
      age. Additionally, if the authors would like tofind the body weight, we can
      employ thefittest equation = 51.930 + 1.673 (Bone and ash weight) where y =
      predicted body weight.

PMID- 17205879
TI  - Family functioning in the families of psychiatric patients: a comparison with
      nonclinical families.
AB  - OBJECTIVE: To examine family functioning in the families of psychiatric patients.
      MATERIAL AND METHOD: Families of psychiatric patients and nonclinical families
      were compared. There were 60 families in each group. The instrument included a
      semistructured interview of family functioning and the Chulalongkorn Family
      Inventory (CFI), a self-report questionnaire designed to assess the perception of
      one's family. RESULTS: From the assessment by semistructured interview, 83.3% of
      psychiatric families and 45.0% of nonclinical families were found to be
      dysfunctional in at least one dimension. The difference was statistically
      significant (p < 0.001). The average number of dysfunctional dimensions in the
      psychiatric families was significantly higher than in the nonclinical control
      group, 3.5 +/- 1.9 and 0.98 +/- 1.5 respectively, p < 0.0001. The CFI scores of
      the psychiatric families were significantly lower than the control group,
      reflecting poor family functioning. The dysfunctions were mostly in the following
      dimensions: problem-solving, communication, affective responsiveness, affective
      involvement, and behavior control. Psychiatric families faced more psychosocial
      stressors and the average number of stressors was higher than the control
      families, 88.3% vs. 56.7% and 4.2 +/- 2.7 vs. 1.3 +/- 1.47 stressors
      respectively, p < 0.0001. CONCLUSION: Family functioning of psychiatric patients
      was less healthy than the nonclinical control. The present study underlined the
      significance of family assessment and family intervention in the comprehensive
      care of psychiatric patients.

PMID- 17205880
TI  - Appropriateness of therapeutic drug monitoring for lithium.
AB  - OBJECTIVE: Evaluate the appropriateness of therapeutic drug monitoring (TDM) for
      lithium. MATERIAL AND METHOD: A retrospective chart review of all patients who
      received lithium for treatment of psychiatric disorders between January 2004 and
      October 2005 was done. The present study was investigated in a psychiatric
      hospital in Thailand Based on detailed chart review, the appropriateness of TDM
      utilization comprised of three aspects, i.e., the indication of TDM request, the
      time of blood sample taking in relation to the medication process, and the
      clinical applications of the reported serum lithium levels, were evaluated. The
      Morecambe Bay Shared Care Guideline 2003 was modified and used as criteria for
      evaluation. Altogether 91 serum lithium samples were measured among 60 patients.
      RESULT: In 66 (72.5%) of requests, clear indications for lithium TDM were
      recorded i.e., initiation therapy 41.8%, suspected toxicity 15.4%, patient
      compliance assessment 5.5%, after regimen changes 5.5%, and therapeutic failure
      4.4%. Routine tests without specified indications were found in the remainder
      (27.5%), all were in-patients, which pointed to potentially redundant use. The
      time of sample taking was recorded in 37 (40.6%) of blood samples, all were taken
      from in-patients, after steady state had been reached. These data for out
      patients were not recorded, except one noted that blood sample was drawn after
      the patient had not received lithium for four days. Serum lithium levels were
      reported in 83 (91.2%) samples. Of these, 37 (44.6%) were out of therapeutic
      range, and only 12 required dosage alterations. The evaluation demonstrated
      somewhat inappropriate use of reported lithium levels. Dose changes were done in
      some patients who required dosage adjustment. Among 14 toxicity-suspected
      patients, nine actually had serum lithium levels exceeding the therapeutic range.
      Of these, only one patient was subsequently switched to a reduced dose, three
      patients were discontinued while five patients were prescribed the pre-TDM doses.
      Similarly, in five toxicity-suspected patients whose serum lithium levels were
      below therapeutic range, lithium was discontinued in three patients and no dosage
      alteration, which was considerably acceptable, in two patients. The doses were
      increased in three out offour inadequately controlled patients whose serum
      lithium was lower than the therapeutic range. Overall, in only 33 (36.3%)
      requests was TDM performed appropriately according to the indication, sampling
      time and subsequent dose adjustment. CONCLUSION: The findings indicate the need
      to improve the utilization of TDM for lithium. Education for hospital personnel
      on appropriateness of serum sample collection, interpretation, and proper use of
      serum drug levels is encouraged. Development of a request form containing
      essential data, such as indication for TDM, current drug dosing regimen, time of
      last dose, patient compliance, test results and interpretations and clinical
      decision made, can help optimize TDM use and reduce unnecessary costs.

PMID- 17205881
TI  - Pregnancy in biliary atresia after kasai operation complicated by portal
      hypertension.
AB  - Hepatic portoenterostomy or Kasai operation has been widely accepted as the
      standard therapy for biliary atresia. Recently, more female patients have grown
      up and reached adulthood; therefore, pregnancy in women with biliary atresia is
      sometimes inevitable. The authors report a 17-year-old woman with biliary atresia
      post Kasai operation at 3 months of age. After the operation, she became jaundice
      free but developed portal hypertension with abnormal liver function. She had
      several episodes of esophageal variceal bleeding and was treated by beta-blocker
      and endoscopic sclerotherapy. Since then, she was lost to follow up for nearly 2
      years. She came back again with 12 weeks of gestation with no symptoms of
      gastrointestinal bleeding for antenatal care. At 32 weeks of gestation, she
      presented with severe hematemesis from variceal bleeding and had thrombocytopenia
      from hypersplenism. She was treated with somatostatin analogue, fluid and blood
      component replacement and other supportive treatments. Cesarean section was
      performed when she was stable at 33 weeks of gestation. After the operation, her
      clinical status was improved and had no other complications. Her baby experienced
      complications of prematurity but improved after treatment. Pregnancy may affect
      the natural course of portal hypertension and worsen the clinical outcome.
      Pregnancy should be avoided in patients with portal hypertension, however it is
      not contraindicated. Pregnancy in biliary atresia patients needs intensive
      prenatal care.

PMID- 17205882
TI  - Successful management of a superior mesenteric artery aneurysm by ligation: a
      case report.
AB  - Superior mesenteric artery aneurysm (SMAA) is a rare entity. Management varies
      from simple ligation with or without revascularization to endovascular placement
      of a covered stent graft. The authors report a case of SMAA who presented with
      retroperitoneal hemorrhage. Diagnosis was made from abdominal computed tomography
      and angiography. The cause of SMAA was not definitely identified but infective
      origin was highly suspicious. The patient underwent successful treatment with
      ligation of the superior mesenteric artery proximal and distal to the SMAA.

PMID- 17205883
TI  - Periosteal chondroma of the proximal humerus: a case report and review of the
      literature.
AB  - Periosteal chondroma is a slow growing benign cartilaginous tumor of bone. It is
      rarely reported among Thai people. The authors present a case ofperiosteal
      chondroma of the proximal humerus. A 14-year-old girl was admitted with a
      painless mass around her left shoulder On magnetic resonance images, a
      subcutaneous lesion with hypointensity on TI-weighted images and marked
      hyperintensity on T2-weighted images, eroded the underlying cortical bone of the
      proximal humerus. The patient underwent marginal excision. There was no
      recurrence of the lesion during 3 years of follow-up.

PMID- 17205884
TI  - Lightwand-assisted nasotracheal intubation in awake ankylosing spondylitis.
AB  - Several techniques of airway management in ankylosing spondylitis (AS) have been
      reported. No study related specifically to the use of a lightwand-assisted
      intubation in AS has been previously described. The present case report
      demonstrates that an awake, nasotracheal intubation can be successfully performed
      to provide general anesthesia in a patient with AS. A 65-year-old Thai male was
      scheduled for exploratory surgery under general anesthesia. Past medical history
      consisted of hypertension and AS. The preoperative airway assessment showed
      limitation of mouth opening, an extremely anteriorly flexed and immobile cervical
      spine. An awake intubation under sedation and topical airway anesthesia were
      chosen. Multiple attempts at blind nasotracheal intubation and oral approach with
      lightwand were unsuccessful. Finally, intubation was successfully performed with
      lightwand by nasal route. This serves to show that an awake nasotracheal
      intubation with a lightwand may be a safe and useful alternative option for
      airway management in patients with severe ankylosing spondylitis.

PMID- 17205885
TI  - Cefazolin induced seizures in hemodialysis patients.
AB  - Cephalosporins are epileptogenic drugs, especially when excessive dosages are
      used or when the drugs are used in patients with decreased renal clearance. The
      present case report showed that a chronic kidney patient receiving hemodialysis
      developed generalized tonic clonic seizures when an inappropriate high dose
      cefazolin was given. Cefazolin 2 g iv q 8 h was given for 25 days continuously to
      treat fever of unknown origin in a patient who was a severe renal impairment
      patient. In a severe renal impairment patient, the maintenance dose of cefazolin
      should be reduced by half and the interval for administration should be extended
      to 24 h. Even though hemodialysis could remove cefazolin from the blood
      circulation, in the presented case the very high dose of cefazolin given was far
      beyond the ability of hemodialysis to clear the drug. The accumulation
      ofcefazolin, therefore, induced three episodes of seizures on days 14, 21 and 25.
      More precaution should be taken when prescribing medication to a patient with
      predisposing factors.

PMID- 17205886
TI  - Intellectual property and patent in stem cell research era.
AB  - Stem cell therapy has obtained much attention, not only for its exceptional
      promise for curing many chronic disorders and degenerative conditions but also
      for its great economic potential. Apart from expenses in research laboratories
      and ongoing clinical trials, intellectual properties, patent of stem cell
      differentiation protocols, and stem cell-derived medical products for cell and
      tissue therapy are of very high cost. Intellectual properties and patents are
      inevitably important issues for stem cell researchers. Stem cell researchers in
      most countries have a chance to develop affordable stem cell therapy, scientific
      progression, and innovations for their patients. However, for this to be done,
      appropriate solutions for international patent barrier must be created so that
      the owner of the original stem cell protocols and techniques can be acknowledge,
      build his reputation and reap reasonable financial benefits. International patent
      barriers will be a crucial step to move the whole stem cell research community
      forward.

PMID- 17205887
TI  - Moral education in medical schools.
AB  - The present report summarizes challenges in teaching medical ethics, defines its
      goals, describes theoretical frameworks for moral education, and reviews
      strategies for teaching medical ethics to serve as guidelines in developing
      medical ethics instruction. Medical teachers should clarify the instructional
      goals in cognitive, attitudinal, and behavioral domains. The cognitive
      developmental and behavior-analytic theories called for ethical instruction using
      a series of discussions based on real-life ethical dilemmas while pointing out
      all the basic rules related to medical practice. Ethical courses for medical
      students should be student-centered, problem-based, and integrative. Ethical
      instruction should be systematically taught to every student, but additional
      elective courses could also be used. Moral education for residents should be more
      focused to issues specific to their specialties. Medical researchers need both
      formal ethical training and informal teaching, and role modeling. Finally,
      experienced staff could use small group discussions of shared ethical problems to
      maintain their ethical knowledge and skills.

PMID- 17205888
TI  - Biological invasions: recommendations for U.S. policy and management.
AB  - The Ecological Society of America has evaluated current U.S. national policies
      and practices on biological invasions in light of current scientific knowledge.
      Invasions by harmful nonnative species are increasing in number and area
      affected; the damages to ecosystems, economic activity, and human welfare are
      accumulating. Without improved strategies based on recent scientific advances and
      increased investments to counter invasions, harm from invasive species is likely
      to accelerate. Federal leadership, with the cooperation of state and local
      governments, is required to increase the effectiveness of prevention of
      invasions, detect and respond quickly to new potentially harmful invasions,
      control and slow the spread of existing invasions, and provide a national center
      to ensure that these efforts are coordinated and cost effective. Specifically,
      the Ecological Society of America recommends that the federal government take the
      following six actions: (1) Use new information and practices to better manage
      commercial and other pathways to reduce the transport and release of potentially
      harmful species; (2) Adopt more quantitative procedures for risk analysis and
      apply them to every species proposed for importation into the country; (3) Use
      new cost-effective diagnostic technologies to increase active surveillance and
      sharing of information about invasive species so that responses to new invasions
      can be more rapid and effective; (4) Create new legal authority and provide
      emergency funding to support rapid responses to emerging invasions; (5) Provide
      funding and incentives for cost-effective programs to slow the spread of existing
      invasive species in order to protect still uninvaded ecosystems, social and
      industrial infrastructure, and human welfare; and (6) Establish a National Center
      for Invasive Species Management (under the existing National Invasive Species
      Council) to coordinate and lead improvements in federal, state, and international
      policies on invasive species. Recent scientific and technical advances provide a
      sound basis for more cost-effective national responses to invasive species.
      Greater investments in improved technology and management practices would be more
      than repaid by reduced damages from current and future invasive species. The
      Ecological Society of America is committed to assist all levels of government and
      provide scientific advice to improve all aspects of invasive-species management.

PMID- 17205889
TI  - The enigma of progress in denitrification research.
AB  - Humans have dramatically increased the amount of reactive nitrogen (primarily
      ammonium, nitrogen oxides, and organically bound N) circulating in the biosphere
      and atmosphere, creating a wide array of desirable products (e.g., food
      production) and undesirable consequences (e.g., eutrophication of aquatic
      ecosystems and air pollution). Only when this reactive N is converted back to the
      chemically unreactive dinitrogen (N2) form, do these cascading effects of
      elevated reactive N cease to be of concern. Among the quantitatively most
      important processes for converting reactive N to N2 gas is the biological process
      of classical denitrification, in which oxides of nitrogen are used as terminal
      electron acceptors in anaerobic respiration. This Invited Feature on
      denitrification includes a series of papers that integrate our current state of
      knowledge across terrestrial, freshwater, and marine systems on denitrification
      rates, controlling factors, and methodologies for measuring and modeling
      denitrification. In this paper, we present an overview of the role of
      denitrification within the broader N cycle, the environmental and health concerns
      that have resulted from human alteration of the N cycle, and a brief historical
      perspective on why denitrification has been so difficult to study. Despite over a
      century of research on denitrification and numerous recent technological
      advances, we still lack a comprehensive, quantitative understanding of
      denitrification rates and controlling factors across ecosystems. Inherent
      problems of measuring spatially and temporally heterogeneous N2 production under
      an N2-rich atmosphere account for much of this slow progress, but lack of
      interdisciplinary communication of research results and methodological
      developments has also impeded denitrification research. An integrated
      multidisciplinary approach to denitrification research, from upland terrestrial
      ecosystems, to small streams, river systems, estuaries, and continental shelf
      ecosystems, and to the open ocean, may yield new insights into denitrification
      across landscapes and waterscapes.

PMID- 17205890
TI  - Denitrification across landscapes and waterscapes: a synthesis.
AB  - Denitrification is a critical process regulating the removal of bioavailable
      nitrogen (N) from natural and human-altered systems. While it has been
      extensively studied in terrestrial, freshwater, and marine systems, there has
      been limited communication among denitrification scientists working in these
      individual systems. Here, we compare rates of denitrification and controlling
      factors across a range of ecosystem types. We suggest that terrestrial,
      freshwater, and marine systems in which denitrification occurs can be organized
      along a continuum ranging from (1) those in which nitrification and
      denitrification are tightly coupled in space and time to (2) those in which
      nitrate production and denitrification are relatively decoupled. In aquatic
      ecosystems, N inputs influence denitrification rates whereas hydrology and
      geomorphology influence the proportion of N inputs that are denitrified.
      Relationships between denitrification and water residence time and N load are
      remarkably similar across lakes, river reaches, estuaries, and continental
      shelves. Spatially distributed global models of denitrification suggest that
      continental shelf sediments account for the largest portion (44%) of total global
      denitrification, followed by terrestrial soils (22%) and oceanic oxygen minimum
      zones (OMZs; 14%). Freshwater systems (groundwater, lakes, rivers) account for
      about 20% and estuaries 1% of total global denitrification. Denitrification of
      land-based N sources is distributed somewhat differently. Within watersheds, the
      amount of land-based N denitrified is generally highest in terrestrial soils,
      with progressively smaller amounts denitrified in groundwater, rivers, lakes and
      reservoirs, and estuaries. A number of regional exceptions to this general trend
      of decreasing denitrification in a downstream direction exist, including
      significant denitrification in continental shelves of N from terrestrial sources.
      Though terrestrial soils and groundwater are responsible for much denitrification
      at the watershed scale, per-area denitrification rates in soils and groundwater
      (kg N x km(-2) x yr(-1)) are, on average, approximately one-tenth the per-area
      rates of denitrification in lakes, rivers, estuaries, continental shelves, or
      OMZs. A number of potential approaches to increase denitrification on the
      landscape, and thus decrease N export to sensitive coastal systems exist.
      However, these have not generally been widely tested for their effectiveness at
      scales required to significantly reduce N export at the whole watershed scale.

PMID- 17205891
TI  - Methods for measuring denitrification: diverse approaches to a difficult problem.
AB  - Denitrification, the reduction of the nitrogen (N) oxides, nitrate (NO3-) and
      nitrite (NO2-), to the gases nitric oxide (NO), nitrous oxide (N2O), and
      dinitrogen (N2), is important to primary production, water quality, and the
      chemistry and physics of the atmosphere at ecosystem, landscape, regional, and
      global scales. Unfortunately, this process is very difficult to measure, and
      existing methods are problematic for different reasons in different places at
      different times. In this paper, we review the major approaches that have been
      taken to measure denitrification in terrestrial and aquatic environments and
      discuss the strengths, weaknesses, and future prospects for the different
      methods. Methodological approaches covered include (1) acetylene-based methods,
      (2) 15N tracers, (3) direct N2 quantification, (4) N2:Ar ratio quantification,
      (5) mass balance approaches, (6) stoichiometric approaches, (7) methods based on
      stable isotopes, (8) in situ gradients with atmospheric environmental tracers,
      and (9) molecular approaches. Our review makes it clear that the prospects for
      improved quantification of denitrification vary greatly in different environments
      and at different scales. While current methodology allows for the production of
      accurate estimates of denitrification at scales relevant to water and air quality
      and ecosystem fertility questions in some systems (e.g., aquatic sediments, well
      defined aquifers), methodology for other systems, especially upland terrestrial
      areas, still needs development. Comparison of mass balance and stoichiometric
      approaches that constrain estimates of denitrification at large scales with point
      measurements (made using multiple methods), in multiple systems, is likely to
      propel more improvement in denitrification methods over the next few years.

PMID- 17205892
TI  - Modeling denitrification in terrestrial and aquatic ecosystems at regional
      scales.
AB  - Quantifying where, when, and how much denitrification occurs on the basis of
      measurements alone remains particularly vexing at virtually all spatial scales.
      As a result, models have become essential tools for integrating current
      understanding of the processes that control denitrification with measurements of
      rate-controlling properties so that the permanent losses of N within landscapes
      can be quantified at watershed and regional scales. In this paper, we describe
      commonly used approaches for modeling denitrification and N cycling processes in
      terrestrial and aquatic ecosystems based on selected examples from the
      literature. We highlight future needs for developing complementary measurements
      and models of denitrification. Most of the approaches described here do not
      explicitly simulate microbial dynamics, but make predictions by representing the
      environmental conditions where denitrification is expected to occur, based on
      conceptualizations of the N cycle and empirical data from field and laboratory
      investigations of the dominant process controls. Models of denitrification in
      terrestrial ecosystems include generally similar rate-controlling variables, but
      vary in their complexity of the descriptions of natural and human-related
      properties of the landscape, reflecting a range of scientific and management
      perspectives. Models of denitrification in aquatic ecosystems range in complexity
      from highly detailed mechanistic simulations of the N cycle to simpler source
      transport models of aggregate N removal processes estimated with empirical
      functions, though all estimate aquatic N removal using first-order reaction rate
      or mass-transfer rate expressions. Both the terrestrial and aquatic modeling
      approaches considered here generally indicate that denitrification is an
      important and highly substantial component of the N cycle over large spatial
      scales. However, the uncertainties of model predictions are large. Future
      progress will be linked to advances in field measurements, spatial databases, and
      model structures.

PMID- 17205893
TI  - Environmental controls on denitrifying communities and denitrification rates:
      insights from molecular methods.
AB  - The advent of molecular techniques has improved our understanding of the
      microbial communities responsible for denitrification and is beginning to address
      their role in controlling denitrification processes. There is a large diversity
      of bacteria, archaea, and fungi capable of denitrification, and their community
      composition is structured by long-term environmental drivers. The range of
      temperature and moisture conditions, substrate availability, competition, and
      disturbances have long-lasting legacies on denitrifier community structure. These
      communities may differ in physiology, environmental tolerances to pH and O2,
      growth rate, and enzyme kinetics. Although factors such as O2, pH, C
      availability, and NO3- pools affect instantaneous rates, these drivers act
      through the biotic community. This review summarizes the results of molecular
      investigations of denitrifier communities in natural environments and provides a
      framework for developing future research for addressing connections between
      denitrifier community structure and function.

PMID- 17205894
TI  - Nitrous oxide nitrification and denitrification 15N enrichment factors from
      Amazon forest soils.
AB  - The isotopic signatures of 15N and 18O in N2O emitted from tropical soils vary
      both spatially and temporally, leading to large uncertainty in the overall
      tropical source signature and thereby limiting the utility of isotopes in
      constraining the global N2O budget. Determining the reasons for spatial and
      temporal variations in isotope signatures requires that we know the isotope
      enrichment factors for nitrification and denitrification, the two processes that
      produce N2O in soils. We have devised a method for measuring these enrichment
      factors using soil incubation experiments and report results from this method for
      three rain forest soils collected in the Brazilian Amazon: soil with differing
      sand and clay content from the Tapajos National Forest (TNF) near Santarem, Para,
      and Nova Vida Farm, Rondonia. The 15N enrichment factors for nitrification and
      denitrification differ with soil texture and site: -111 per thousand +/- 12 per
      thousand and -31 per thousand +/- 11 per thousand for a clay-rich Oxisol (TNF), 
      102 per thousand +/- 5 per thousand and -45 per thousand +/- 5 per thousand for a
      sandier Ultisol (TNF), and -10.4 per thousand +/- 3.5 per thousand (enrichment
      factor for denitrification) for another Ultisol (Nova Vida) soil, respectively.
      We also show that the isotopomer site preference (delta15Nalpha - delta15Nbeta,
      where alpha indicates the central nitrogen atom and beta the terminal nitrogen
      atom in N2O) may allow differentiation between processes of production and
      consumption of N2O and can potentially be used to determine the contributions of
      nitrification and denitrification. The site preferences for nitrification and
      denitrification from the TNF-Ultisol incubated soils are: 4.2 per thousand +/-
      8.4 per thousand and 31.6 per thousand +/- 8.1 per thousand, respectively. Thus,
      nitrifying and denitrifying bacteria populations under the conditions of our
      study exhibit significantly different 15N site preference fingerprints. Our data
      set strongly suggests that N2O isotopomers can be used in concert with
      traditional N2O stable isotope measurements as constraints to differentiate
      microbial N2O processes in soil and will contribute to interpretations of the
      isotopic site preference N2O values found in the free troposphere.

PMID- 17205895
TI  - N fertilization effects on denitrification and N cycling in an aggrading forest.
AB  - We investigated N cycling and denitrification rates following five years of N and
      dolomite amendments to whole-tree harvested forest plots at the long-term soil
      productivity experiment in the Fernow Experimental Forest in West Virginia, USA.
      We hypothesized that changes in soil chemistry and nutrient cycling induced by N
      fertilization would increase denitrification rates and the N2O:N2 ratio. Soils
      from the fertilized plots had a lower pH (2.96) than control plots (3.22) and
      plots that received fertilizer and dolomite (3.41). There were no significant
      differences in soil %C or %N between treatments. Chloroform-labile microbial
      biomass carbon was lower in fertilized plots compared to control plots, though
      this trend was not significant. Extractable soil NO3- was elevated in fertilized
      plots on each sample date. Soil-extractable NH4+, NO3-, pH, microbial biomass
      carbon, and %C varied significantly by sample date suggesting important seasonal
      patterns in soil chemistry and N cycling. In particular, the steep decline in
      extractable NH4+ during the growing season is consistent with the high N demands
      of a regenerating forest. Net N mineralization and nitrification also varied by
      date but were not affected by the fertilization and dolomite treatments. In a
      laboratory experiment, denitrification was stimulated by NO3- additions in soils
      collected from all field plots, but this effect was stronger in soils from the
      unfertilized control plots, suggesting that chronic N fertilization has partially
      alleviated a NO3- limitation on denitrification rates. Dextrose stimulated
      denitrification only in the whole-tree-harvest soils. Denitrification enzyme
      activity varied by sample date and was elevated in fertilized plots for soil
      collected in July 2000 and June 2001. There were no detectable treatment effects
      on N2O or N2 flux from soils under anaerobic conditions, though there was strong
      temporal variation. These results suggest that whole-tree harvesting has altered
      the N status of these soils so they are less prone to N saturation than more
      mature forests. It is likely that N losses associated with the initial harvest
      and high N demand by aggrading vegetation is minimizing, at least temporarily,
      the amount of inorganic N available for nitrification and denitrification, even
      in the fertilized plots in this experiment.

PMID- 17205896
TI  - Denitrification and the nitrogen budget of a reservoir in an agricultural
      landscape.
AB  - Denitrification is an important process in aquatic sediments, but its role has
      not been assessed in the N mass balance of upper-Midwestern (USA) reservoirs that
      receive large agricultural riverine N inputs. We used a 4400-ha reservoir to
      determine the role of denitrification in the N mass balance and effectiveness in
      reducing downstream transport of NO(3-)N. Sediment denitrification was (1)
      measured monthly (March 2002-March 2003) at eight sites in the Lake Shelbyville
      reservoir in central Illinois using the acetylene inhibition, chloramphenicol
      technique, (2) scaled to the overall reservoir and compared to N not accounted
      for in a mass balance, and (3) estimated indirectly using long-term (1981-2003)
      mass balances of N in the reservoir. Denitrification rates in the reservoir were
      high during spring and early summer of 2002, when maximum NO(3-)N concentrations
      were measured (10-14 mg NO(3-)N/L). We estimated that denitrification for the
      year was between 2580 and 5150 Mg N. Missing N from the mass balance was 3004 Mg
      N, suggesting that sediment denitrification was the sink. Areal rates of sediment
      denitrification in the reservoir ranged from 62 to 225 g N x m(-2) x yr(-1), with
      rates a function of both denitrification intensity (microg N x g dry mass x h(
      1)) and the overall mass of sediment present. From 1981 to 2003 the average NO(3
      )N inlet flux was 8900 Mg N/yr. About 58% of the total NO(3-)N input was removed,
      and annual NO(3-)N removed as a percentage of inputs was significantly related to
      reservoir retention time (average = 0.36 yr for the 23 years, range = 0.21-0.84
      yr). By scaling denitrification in Lake Shelbyville to other reservoirs in
      Illinois, we estimated a sink of 48900 Mg N/yr. When combined with estimated in
      stream denitrification, 60900 Mg N/yr was estimated to be removed by sediment
      denitrification. This reduces riverine export from Illinois to the Gulf of
      Mexico, where the flux during the 1990s was about 244000 Mg N/yr, and illustrates
      the importance of reservoir denitrification as an N sink in Midwestern
      agricultural landscapes.

PMID- 17205897
TI  - Denitrification in nitrate-rich streams: application of N2:Ar and 15N-tracer
      methods in intact cores.
AB  - Rates of benthic denitrification were measured using two techniques, membrane
      inlet mass spectrometry (MIMS) and isotope ratio mass spectrometry (IRMS),
      applied to sediment cores from two NO3(-)-rich streams draining agricultural land
      in the upper Mississippi River Basin. Denitrification was estimated
      simultaneously from measurements of N2:Ar (MIMS) and 15N[N2] (IRMS) after the
      addition of low-level 15NO3- tracer (15N:N = 0.03-0.08) in stream water overlying
      intact sediment cores. Denitrification rates ranged from about 0 to 4400 micromol
      N x m(-2) x h(-1) in Sugar Creek and from 0 to 1300 micromol N x m(-2) x h(-1) in
      Iroquois River, the latter of which possesses greater streamflow discharge and a
      more homogeneous streambed and water column. Within the uncertainties of the two
      techniques, there is good agreement between the MIMS and IRMS results, which
      indicates that the production of N2 by the coupled process of
      nitrification/denitrification was relatively unimportant and surface-water NO3-
      was the dominant source of NO3- for benthic denitrification in these streams.
      Variation in stream NO3- concentration (from about 20 micromol/L during low
      discharge to 1000 micromol/L during high discharge) was a significant control of
      benthic denitrification rates, judging from the more abundant MIMS data. The
      interpretation that NO3- concentration directly affects denitrification rate was
      corroborated by increased rates of denitrification in cores amended with NO3-.
      Denitrification in Sugar Creek removed < or = 11% per day of the instream NO3- in
      late spring and removed roughly 15-20% in late summer. The fraction of NO3-
      removed in Iroquois River was less than that of Sugar Creek. Although benthic
      denitrification rates were relatively high during periods of high stream flow,
      when NO3 concentrations were also high, the increase in benthic denitrification
      could not compensate for the much larger increase in stream NO3- fluxes during
      high flow. Consequently, fractional NO3- losses were relatively low during high
      flow.

PMID- 17205898
TI  - Dynamics of prion disease transmission in mule deer.
AB  - Chronic wasting disease (CWD), a contagious prion disease of the deer family, has
      the potential to severely harm deer populations and disrupt ecosystems where deer
      occur in abundance. Consequently, understanding the dynamics of this emerging
      infectious disease, and particularly the dynamics of its transmission, has
      emerged as an important challenge for contemporary ecologists and wildlife
      managers. Although CWD is contagious among deer, the relative importance of
      pathways for its transmission remains unclear. We developed seven competing
      models, and then used data from two CWD outbreaks in captive mule deer and model
      selection to compare them. We found that models portraying indirect transmission
      through the environment had 3.8 times more support in the data than models
      representing transmission by direct contact between infected and susceptible
      deer. Model-averaged estimates of the basic reproductive number (R0) were 1.3 or
      greater, indicating likely local persistence of CWD in natural populations under
      conditions resembling those we studied. Our findings demonstrate the apparent
      importance of indirect, environmental transmission in CWD and the challenges this
      presents for controlling the disease.

PMID- 17205899
TI  - Test of a behavior-based individual-based model: response of shorebird mortality
      to habitat loss.
AB  - In behavior-based individual-based models (IBMs), demographic functions are
      emergent properties of the model and are not built into the model structure
      itself, as is the case with the more widely used demography-based IBMs. Our
      behavior-based IBM represents the physiology and behavioral decision making of
      individual animals and, from that, predicts how many survive the winter
      nonbreeding season, an important component of fitness. This paper provides the
      first test of such a model by predicting the change in winter mortality of a
      charadriid shorebird following removal of intertidal feeding habitat, the main
      effect of which was to increase bird density. After adjusting one calibration
      parameter to the level required to replicate the observed mortality rate before
      habitat loss, the model predicted that mortality would increase by 3.65%, which
      compares well with the observed increase of 3.17%. The implication that mortality
      was density-dependent was confirmed by predicting mortality over a range of bird
      densities. Further simulations showed that the density dependence was due to an
      increase in both interference and depletion competition as bird density
      increased. Other simulations suggested that an additional area of mudflat,
      equivalent to only 10% of the area that had been lost, would be needed by way of
      mitigation to return mortality to its original level. Being situated at a high
      shore level with the flow of water in and out impeded by inlet pipes, the
      mitigating mudflat would be accessible to birds when all mudflats in the estuary
      were covered at high tide, thus providing the birds with extra feeding time and
      not just a small replacement mudflat. Apart from providing the first, and
      confidence-raising, test of a behavior-based IBM, the results suggest (1) that
      the chosen calibration procedure was effective; (2) that where no new fieldwork
      is required, and despite being parameter rich, a behavior-based IBM can be
      parameterized quickly (few weeks), and thus cheaply, because so many of the
      parameter values can be obtained from the literature and are embedded in the
      model; and (3) that behavior-based IBMs can be used to explore system behavior
      (e.g., the role of depletion competition and interference competition in density
      dependent mortality).

PMID- 17205900
TI  - Landscape history, fragmentation, and patch occupancy: models for a forest bird
      with limited dispersal.
AB  - We developed and tested patch occupancy models for an endemic understory bird
      with limited dispersal ability, the Chucao Tapaculo (Scelorchilus rubecula), in
      two South American temperate rain forest landscapes that differed in levels and
      duration of forest loss. We assessed cover changes since 1961 in each landscape
      and surveyed patches for Chucao Tapaculo occupancy. We then developed incidence
      based predictive models independently for each landscape and tested each model
      reciprocally in the alternative study area. We thereby assessed the domain of
      model applicability and identified those predictor variables with general effects
      and those that varied between the two landscapes. The two models were consistent
      regarding variable selection, and predictive accuracy of each model was high in
      the landscape where training data were collected. However, the models differed
      substantially in the magnitudes of effects related to patch size, with larger
      unoccupied patches observed in the landscape with the more advanced stage of
      fragmentation. Due to this discrepancy, each model performed poorly when applied
      to the alternative landscape, potentially reflecting the contrasting stages of
      habitat loss. Although it was impossible to dissociate effects of level and
      duration of forest loss, we viewed the landscapes as representing two extremes
      along a continuum of fragmentation, providing insights into potential
      trajectories for portions of the biome where deforestation is occurring. Further,
      our data suggest that static equilibrium models developed from distribution
      patterns in recently fragmented landscapes may overestimate persistence when used
      as a forecasting tool, or when extrapolated to alternative landscapes where
      fragmentation is more advanced. Thus, we suggest that landscapes used as
      standards for model building should be selected with caution. We recommend that
      distribution patterns be obtained from landscapes where fragmentation is
      advanced, preferably with histories of fragmentation long enough that time
      delayed extinctions already would have occurred.

PMID- 17205901
TI  - Grassland songbirds in a dynamic management landscape: behavioral responses and
      management strategies.
AB  - In recent decades, earlier and more frequent harvests of agricultural grasslands
      have been implicated as a major cause of population declines in grassland
      songbirds. From 2002 to 2005, in the Champlain Valley of Vermont and New York,
      USA, we studied the reproductive success of Savannah Sparrows (Passerculus
      sandwichensis) and Bobolinks (Dolichonyx oryzivorus) on four grassland
      treatments: (1) early-hayed fields cut before 11 June and again in early- to mid
      July; (2) middle-hayed fields cut once between 21 June and 10 July; (3) late
      hayed fields cut after 1 August; and (4) rotationally grazed pastures. Both the
      number of fledglings per female per year and nest success (logistic-exposure
      method) varied among treatments and between species. Although birds initiated
      nests earlier on early-hayed fields compared to others, haying caused 99% of
      active Savannah Sparrow and 100% of active Bobolink nests to fail. Both the
      initial cutting date and time between cuttings influenced renesting behavior.
      After haying, Savannah Sparrows generally remained on early-hayed fields and
      immediately renested (clutch completion 15.6 +/- 1.28 days post-haying; all
      values are reported as mean +/- SE), while Bobolinks abandoned the fields for at
      least two weeks (mean clutch completion 33 +/- 0.82 days post-haying). While
      female Savannah Sparrows fledged more offspring per year (1.28 +/- 0.16) than
      female Bobolinks (0.05 +/- 0.05), reproductive success on early-hayed fields was
      low. The number of fledglings per female per year was greater on middle-hayed
      fields (Savannah Sparrows, 3.47 +/- 0.42; Bobolinks, 2.22 +/- 0.26), and late
      hayed fields (Savannah Sparrows, 3.29 +/- 0.30; Bobolinks, 2.79 +/- 0.18).
      Reproductive success was moderate on rotationally grazed pastures, where female
      Savannah Sparrows and female Bobolinks produced 2.32 +/- 0.25 and 1.79 +/- 0.33
      fledgling per year, respectively. We simultaneously conducted cutting surveys
      throughout the Champlain Valley and found that 3-8% of hayfield habitat was cut
      by 1-4 June, 25-40% by 12-16 June, and 32-60% by 28 June-2 July. Thus, the
      majority of grassland habitat was cut during the breeding season; however, late
      hayed fields served as high-quality reserves for late-nesting female Bobolinks
      that were displaced from previously hayed fields. For fields first cut in May, a
      65-day interval between cuts could provide enough time for both species to
      successfully fledge young.

PMID- 17205902
TI  - Dispersal per recruit: an efficient method for assessing sustainability in marine
      reserve networks.
AB  - Marine reserves are an increasingly important tool for the management of marine
      ecosystems around the world. However, the effects of proposed marine reserve
      configurations on sustainability and yield of populations are typically not
      estimated because of the computational intensity of direct simulation and
      uncertainty in larval dispersal and density-dependent recruitment. Here we
      develop a method for efficiently assessing a marine reserve configuration for
      persistence and yield of a population with sedentary adults and dispersing
      larvae. The method extends the familiar sustainability criteria of individual
      replacement for single populations based on eggs-per-recruit (EPR) to spatially
      distributed populations with sedentary adults, a dispersing larval phase, and
      limited carrying capacity in the settlement-recruit relationship. We refer to
      this approach as dispersal-per-recruit (DPR). In some cases, a single DPR
      calculation, based on the assumption that post-settlement habitat is saturated
      (i.e., at maximum recruitment), is sufficient to determine population
      persistence, while in other cases further iterative calculations are required.
      These additional calculations reach an equilibrium more rapidly than a full
      simulation of age- or size-structured populations. From the DPR result, fishery
      yield can be computed from yield-per-recruit (YPR) at each point. We assess the
      utility of DPR calculations by applying them to single reserves, uniformly
      distributed systems of reserves, and randomly sized and spaced systems of
      reserves on a linear coastline. We find that for low levels of EPR in fished
      areas (e.g., 10% or less of the natural, unfished EPR when post-settlement
      habitats are saturated by 35% of natural settlement), a single DPR calculation is
      sufficient to determine persistence of the population. We also show that, in
      uniform systems of reserves with finite reserve size, maximal fisheries yield
      occurs when the density of reserves is such that all post-settlement habitat is
      nearly saturated with settlers. Finally, we demonstrate the application of this
      approach to a realistic proposed marine reserve configuration.

PMID- 17205903
TI  - Robustness of surrogates of biodiversity in marine benthic communities.
AB  - The usefulness of surrogates to estimate complex variables describing community
      structure, such as the various components of biodiversity, is long established.
      Most attention has been given to surrogates of species richness and species
      diversity and has focused on identifying a subset of taxa as a surrogate of total
      community richness or diversity. In adopting a surrogate measure, it is assumed
      that the relationship between the surrogate(s) and total richness or diversity is
      consistent in both space and time. These assumptions are rarely examined
      explicitly. We examined the robustness of potential surrogates of familial
      richness and multivariate community structure for macrofauna communities
      inhabiting artificial kelp holdfasts by comparing among communities of dissimilar
      ages and among communities established at different times of the year. This is
      important because most benthic "landscapes" will be a mosaic of patches
      reflecting different intensities, frequencies, and timing of disturbances. The
      total abundance of organisms and familial richness of crustaceans or polychaetes
      were all good predictors of total familial richness (R2 > 0.68). In contrast,
      while the familial richness of other groups, such as mollusks and echinoderms,
      were well correlated with total familial richness for communities at an early
      stage of development, the strength of these relationships declined with community
      age. For multivariate community structure, carefully selected subsets of
      approximately 10% of the total taxa yielded similar patterns to the total suite
      of taxa, irrespective of the age of the community. Thus, useful surrogates of
      both familial richness and multivariate community structure can be identified for
      this type of community. However, the choice of technique for selecting surrogate
      taxa largely depends on the nature of the pilot data available, and careful
      selection is required to ensure that surrogates perform consistently across
      different-aged communities. While the specific taxa selected as surrogates will
      vary among different communities, and possibly even among similar communities at
      different sites, the techniques and the concepts we address are applicable to any
      community type.

PMID- 17205904
TI  - Continued decline of an Atlantic cod population: how important is gray seal
      predation?
AB  - The continental shelf ecosystem on the Eastern Scotian Shelf (ESS) has
      experienced drastic changes. Once common top predators are a small fraction of
      their historical abundance, and much of the current community structure is now
      dominated by pelagic fishes and invertebrates. Embedded within this food web,
      Atlantic cod and gray seal populations have recently exhibited nearly opposite
      trends. Since 1984, cod populations have decreased exponentially at a rate
      averaging 17% per year, whereas gray seals have continued to increase
      exponentially at a rate of 12%. We reexamined the impact of gray seals on
      Atlantic cod dynamics using more than 30 years of data on the population trends
      of cod and gray seals while incorporating new information on seal diet and
      seasonal distribution. The closure of the cod fishery over 10 years ago allowed
      for a better estimation of natural mortality rates. We quantified the impact of
      seals on ESS cod by (1) estimating trends in seal and cod abundance, (2)
      estimating the total energy needed for seal growth and maintenance from an
      energetics model, (3) using estimates of the percentage of cod in the total diet
      derived from quantitative fatty acid signature analysis (QFASA) and of the size
      specific selectivity of cod consumed (derived from otoliths collected from fecal
      samples), and (4) assuming a gray seal functional response. Uncertainties of the
      model estimates were calculated using the Hessian approximation of the variance
      covariance matrix. Between 1993 and 2000, cod comprised, on average, < 5% of a
      gray seal's diet. Our model shows that, since the closure of the fishery, gray
      seals have imposed a significant level of instantaneous mortality (0.21), and
      along with other unknown sources of natural mortality (0.62), are contributing to
      the failure of this cod stock to recover.

PMID- 17205905
TI  - Incorporating diverse data and realistic complexity into demographic estimation
      procedures for sea otters.
AB  - Reliable information on historical and current population dynamics is central to
      understanding patterns of growth and decline in animal populations. We developed
      a maximum likelihood-based analysis to estimate spatial and temporal trends in
      age/sex-specific survival rates for the threatened southern sea otter (Enhydra
      lutris nereis), using annual population censuses and the age structure of
      salvaged carcass collections. We evaluated a wide range of possible spatial and
      temporal effects and used model averaging to incorporate model uncertainty into
      the resulting estimates of key vital rates and their variances. We compared these
      results to current demographic parameters estimated in a telemetry-based study
      conducted between 2001 and 2004. These results show that survival has decreased
      substantially from the early 1990s to the present and is generally lowest in the
      north-central portion of the population's range. The greatest temporal decrease
      in survival was for adult females, and variation in the survival of this age/sex
      class is primarily responsible for regulating population growth and driving
      population trends. Our results can be used to focus future research on southern
      sea otters by highlighting the life history stages and mortality factors most
      relevant to conservation. More broadly, we have illustrated how the powerful and
      relatively straightforward tools of information-theoretic-based model fitting can
      be used to sort through and parameterize quite complex demographic modeling
      frameworks.

PMID- 17205906
TI  - Homogenization dynamics and introduction routes of invasive freshwater fish in
      the Iberian Peninsula.
AB  - Nonnative invasive species are one of the main global threats to biodiversity.
      The understanding of the traits characterizing successful invaders and invasion
      prone ecosystems is increasing, but our predictive ability is still limited.
      Quantitative information on biotic homogenization and particularly its temporal
      dynamics is even scarcer. We used freshwater fish distribution data in the
      Iberian Peninsula in four periods (before human intervention, 1991, 1995, and
      2001) to assess the temporal dynamics of biotic homogenization among river
      basins. The percentage of introduced species among fish faunas has increased in
      recent times (from 41.8% in 1991 to 52.5% in 2001), leading to a clear increase
      in the similarity of community composition among basins. The mean Jaccard's index
      increase (a measure of biotic homogenization) from the pristine situation to the
      present (17.1%) was similar to that for Californian fish but higher than for
      other studies. However, biotic homogenization was found to be a temporally
      dynamic process, with finer temporal grain analyses detecting transient stages of
      biotic differentiation. Introduced species assemblages were spatially structured
      along a latitudinal gradient in the Iberian Peninsula, with species related to
      sport fishing being characteristic of northern basins. Although the comparison of
      fish distributions in the Iberian Peninsula and France showed significant and
      generalized biotic homogenization, nonnative assemblages of northeastern Iberian
      basins were more similar to those of France than to those of the rest of the
      Iberian Peninsula, indicating a main introduction route. Species introduced to
      the Iberian Peninsula tended to be mainly piscivores or widely introduced species
      that previously had been introduced to France. Our results indicate that the
      simultaneous analysis of the spatial distribution of introduced assemblages
      (excluding native species that reflect other biogeographical patterns) and their
      specific traits can be an effective tool to detect introduction and invasion
      routes and to predict future invaders from donor regions.

PMID- 17205907
TI  - Atrazine increases ranavirus susceptibility in the tiger salamander, Ambystoma
      tigrinum.
AB  - Pathogenic diseases and environmental contaminants are two of the leading
      hypotheses for global amphibian declines, yet few studies have examined the
      influence of contaminants on disease susceptibility. In this study, we examined
      effects of ecologically relevant doses of atrazine (0, 1.6, 16, and 160
      microg/L), sodium nitrate (0, 6.8, 68 mg/L), and their interactions on
      susceptibility of four laboratory-bred tiger salamander families to Ambystoma
      tigrinum virus (ATV), a pathogen implicated in global amphibian die-offs.
      Salamanders were from Arizona populations where a coevolutionary history with ATV
      is supported, and thus cofactors rather than recent introduction may contribute
      to disease epizootics. Use of atrazine and nitrogenous fertilizers are
      ubiquitous; therefore, the impact of these cofactors on disease susceptibility is
      an important consideration. Atrazine and sodium nitrate significantly decreased
      peripheral leukocyte levels, suggesting an impact of these contaminants on the
      immune system. As expected from this result, atrazine significantly increased
      susceptibility of larvae to ATV infection. In contrast, nitrate had a marginally
      significant main effect and significantly decreased infection rate at the highest
      level. However, neither atrazine nor sodium nitrate had significant effects on
      viral copy number per individual. These results suggest that ecologically
      relevant concentrations of atrazine and nitrates have immunosuppressive effects,
      and atrazine may contribute to ATV epizootics, raising concerns about the
      influence of contaminants on diseases in general.

PMID- 17205908
TI  - Interspecific resource partitioning in sympatric ursids.
AB  - The fundamental niche of a species is rarely if ever realized because the
      presence of other species restricts it to a narrower range of ecological
      conditions. The effects of this narrower range of conditions define how resources
      are partitioned. Resource partitioning has been inferred but not demonstrated
      previously for sympatric ursids. We estimated assimilated diet in relation to
      body condition (body fat and lean and total body mass) and reproduction for
      sympatric brown bears (Ursus arctos) and American black bears (U. americanus) in
      south-central Alaska, 1998-2000. Based on isotopic analysis of blood and keratin
      in claws, salmon (Oncorhynchus spp.) predominated in brown bear diets (> 53%
      annually) whereas black bears assimilated 0-25% salmon annually. Black bears did
      not exploit salmon during a year with below average spawning numbers, probably
      because brown bears deterred black bear access to salmon. Proportion of salmon in
      assimilated diet was consistent across years for brown bears and represented the
      major portion of their diet. Body size of brown bears in the study area
      approached mean body size of several coastal brown bear populations,
      demonstrating the importance of salmon availability to body condition. Black
      bears occurred at a comparable density (mass:mass), but body condition varied and
      was related directly to the amount of salmon assimilated in their diet. Both
      species gained most lean body mass during spring and all body fat during summer
      when salmon were present. Improved body condition (i.e., increased percentage
      body fat) from salmon consumption reduced catabolism of lean body mass during
      hibernation, resulting in better body condition the following spring. Further,
      black bear reproduction was directly related to body condition; reproductive
      rates were reduced when body condition was lower. High body fat content across
      years for brown bears was reflected in consistently high reproductive levels. We
      suggest that the fundamental niche of black bears was constrained by brown bears
      through partitioning of food resources, which varied among years. Reduced
      exploitation of salmon caused black bears to rely more extensively on less
      reliable or nutritious food sources (e.g., moose [Alces alces], berries)
      resulting in lowered body condition and subsequent reproduction.

PMID- 17205909
TI  - Litter and dead wood dynamics in ponderosa pine forests along a 160-year
      chronosequence.
AB  - Disturbances such as fire play a key role in controlling ecosystem structure. In
      fire-prone forests, organic detritus comprises a large pool of carbon and can
      control the frequency and intensity of fire. The ponderosa pine forests of the
      Colorado Front Range, USA, where fire has been suppressed for a century, provide
      an ideal system for studying the long-term dynamics of detrital pools. Our
      objectives were (1) to quantify the long-term temporal dynamics of detrital
      pools; and (2) to determine to what extent present stand structure, topography,
      and soils constrain these dynamics. We collected data on downed dead wood,
      litter, duff (partially decomposed litter on the forest floor), stand structure,
      topographic position, and soils for 31 sites along a 160-year chronosequence. We
      developed a compartment model and parameterized it to describe the temporal
      trends in the detrital pools. We then developed four sets of statistical models,
      quantifying the hypothesized relationship between pool size and (1) stand
      structure, (2) topography, (3) soils variables, and (4) time since fire. We
      contrasted how much support each hypothesis had in the data using Akaike's
      Information Criterion (AIC). Time since fire explained 39-80% of the variability
      in dead wood of different size classes. Pool size increased to a peak as material
      killed by the fire fell, then decomposed rapidly to a minimum (61-85 years after
      fire for the different pools). It then increased, presumably as new detritus was
      produced by the regenerating stand. Litter was most strongly related to canopy
      cover (r2 = 77%), suggesting that litter fall, rather than decomposition,
      controls its dynamics. The temporal dynamics of duff were the hardest to predict.
      Detrital pool sizes were more strongly related to time since fire than to
      environmental variables. Woody debris peak-to-minimum time was 46-67 years,
      overlapping the range of historical fire return intervals (1 to > 100 years).
      Fires may therefore have burned under a wide range of fuel conditions, supporting
      the hypothesis that this region's fire regime was mixed severity.

PMID- 17205910
TI  - Regional and phylogenetic variation of wood density across 2456 Neotropical tree
      species.
AB  - Wood density is a crucial variable in carbon accounting programs of both
      secondary and old-growth tropical forests. It also is the best single descriptor
      of wood: it correlates with numerous morphological, mechanical, physiological,
      and ecological properties. To explore the extent to which wood density could be
      estimated for rare or poorly censused taxa, and possible sources of variation in
      this trait, we analyzed regional, taxonomic, and phylogenetic variation in wood
      density among 2456 tree species from Central and South America. Wood density
      varied over more than one order of magnitude across species, with an overall mean
      of 0.645 g/cm3. Our geographical analysis showed significant decreases in wood
      density with increasing altitude and significant differences among low-altitude
      geographical regions: wet forests of Central America and western Amazonia have
      significantly lower mean wood density than dry forests of Central and South
      America, eastern and central Amazonian forests, and the Atlantic forests of
      Brazil; and eastern Amazonian forests have lower wood densities than the dry
      forests and the Atlantic forest. A nested analysis of variance showed that 74% of
      the species-level wood density variation was explained at the genus level, 34% at
      the Angiosperm Phylogeny Group (APG) family level, and 19% at the APG order
      level. This indicates that genus-level means give reliable approximations of
      values of species, except in a few hypervariable genera. We also studied which
      evolutionary shifts in wood density occurred in the phylogeny of seed plants
      using a composite phylogenetic tree. Major changes were observed at deep nodes
      (Eurosid 1), and also in more recent divergences (for instance in the Rhamnoids,
      Simaroubaceae, and Anacardiaceae). Our unprecedented wood density data set yields
      consistent guidelines for estimating wood densities when species-level
      information is lacking and should significantly reduce error in Central and South
      American carbon accounting programs.

PMID- 17205911
TI  - Physiological and developmental effects of O3 on cottonwood growth in urban and
      rural sites.
AB  - Previously we found that cloned cottonwood saplings (Populus deltoides) grew
      twice as large in New York, New York, USA, compared to surrounding rural
      environments and that soils, temperature, CO2, nutrient deposition, and
      microclimatic variables could not account for the greater urban plant biomass.
      Correlations between final season biomass and cumulative O3 exposures, combined
      with twofold growth reductions in an open-top chamber experiment provided strong
      evidence that higher cumulative O3 exposures in rural sites reduced growth in the
      country. Here, we assess the field gas exchange, growth and development, and
      allocation responses underlying the observed growth differences and compare them
      with isolated O3 responses documented in the open-top chamber experiment.
      Cottonwoods showed no visible foliar injury, reduced photosynthesis of recently
      expanded foliage, early leaf senescence, protective reduction in stomatal
      conductance, or compensatory allocation to shoot relative to root biomass for
      either the chamber or field experiment. Instead, O3-impacted chamber plants had
      significantly higher conductance and reduced photosynthesis of older foliage that
      led to reduced leaf area production and a twofold biomass reduction in the
      absence of visible injury. Rural-grown field plants showed the same pattern of
      significantly higher conductance in the absence of concomitant increases in
      photosynthesis that was indicative of a loss of stomatal control. Incremental
      changes in foliar production were also significantly inversely related to
      fluctuations in ambient O3 exposures. The similarity in biomass, gas exchange,
      phenological, and allocation responses between chamber and field experiments
      indicate that mechanisms accounting for reduced growth at rural sites were
      consistent with those in the open-top chamber O3 experiment. This study shows the
      limitation of visible symptoms as a sole diagnostic factor for documenting
      detrimental O3 impacts and points toward a new approach to show O3 impacts when
      visible injury is not present. Namely, O3-impacted vegetation showed an unusual
      inverse relationship of increased conductance with lower photosynthesis of older
      foliage that was indicative of a loss of stomatal control. This increased
      stomatal conductance of O3-impacted vegetation accentuates pollutant flux into
      affected foliage and has important implications for system water balance during
      warm, dry portions of the growing season when O3 concentrations are highest.

PMID- 17205912
TI  - Multiple plant exploiters on a shared host: testing for nonadditive effects on
      plant performance.
AB  - The combined impact of multiple plant parasites on plant performance can either
      be additive (the total damage equals the sum of the individual effects) or
      nonadditive (synergistic or antagonistic damage). Two statistical models are
      available for testing the independent (=additive) effects of two factors. Here we
      suggest that the natural history of the plant-parasite system should motivate the
      choice of a statistical model to test for additivity. Using in-field,
      manipulative experiments, we examined the interactions between the herbivorous
      mite Calacarus flagelliseta Fletchmann, De Moraes and Barbosa (Acari:
      Eriophyidae), the fungal pathogen Oidium caricae F. Noack (a powdery mildew), and
      their host plant Carica papaya L. in Hawaii. First, we found that herbivorous
      mites had a moderate negative effect on powdery mildew: when mites were absent,
      powdery mildew colonies were larger and more numerous. Second, we showed that
      each plant parasite, when evaluated alone, significantly reduced several measures
      of plant performance. Third, we found that the combined impact of mites and
      mildew on plant performance is mostly additive and, for a few variables, less
      than additive. Finally, we explored compensatory responses and found no evidence
      for nonlinearities in the relationship between plant performance and cumulative
      parasite impact. Plants are almost universally subject to attack by multiple
      herbivores and pathogens; thus a deeper understanding of how multiple plant
      parasites shape each other's population dynamics and plant performance is
      essential to understanding plant-parasite interactions.

PMID- 17205913
TI  - Demographic models inform selection of biocontrol agents for garlic mustard
      (Alliaria petiolata).
AB  - Nonindigenous invasive plants pose a major threat to natural communities
      worldwide. Biological control of weeds via selected introduction of their natural
      enemies can affect control over large spatial areas but also risk nontarget
      effects. To maximize effectiveness while minimizing risk, weed biocontrol
      programs should introduce the minimum number of host-specific natural enemies
      necessary to control an invasive nonindigenous plant. We used elasticity analysis
      of a matrix model to help inform biocontrol agent selection for garlic mustard
      (Alliaria petiolata (M. Bieb.) Cavara and Grande). The Eurasian biennial A.
      petiolata is considered one of the most problematic invaders of temperate forests
      in North America. Four weevil species in the genus Ceutorhynchus (Coleoptera:
      Curculionidae) are currently considered potential biocontrol agents. These
      species attack rosettes (C. scrobicollis), stems (C. roberti, C. alliariae), and
      seeds (C. constrictus) of A. petiolata. Elasticity analyses using A. petiolata
      demographic parameters from North America indicated that changes in the rosette
      to-flowering-plant transition and changes in fecundity consistently had the
      greatest impact on population growth rate. These results suggest that attack by
      the rosette-feeder C. scrobicollis, which reduces overwintering survival, and
      seed or stem feeders that reduce seed output should be particularly effective.
      Model outcomes differed greatly as A. petiolata demographic parameters were
      varied within ranges observed in North America, indicating that successful
      control of A. petiolata populations may occur under some, but not all,
      conditions. Using these a priori analyses we predict: (1) rosette mortality and
      reduction of seed output will be the most important factors determining A.
      petiolata demography; (2) the root-crown feeder C. scrobicollis will have the
      most significant impact on A. petiolata demography; (3) releases of single
      control agents are unlikely to control A. petiolata across its full range of
      demographic variability; (4) combinations of agents that simultaneously reduce
      rosette survival and seed production will be required to suppress the most
      vigorous A. petiolata populations. These predictions can be tested using
      established long-term monitoring sites coupled with a designed release program.
      If demographic models can successfully predict biocontrol agent impact on
      invasive plant populations, a continued dialogue and collaboration between
      empirical and theoretical approaches may be the key to the development of
      successful biocontrol tactics for plant invaders in the future.

PMID- 17205914
TI  - Deconstructing adaptive management: criteria for applications to environmental
      management.
AB  - The concept of adaptive management has, for many ecologists, become a foundation
      of effective environmental management for initiatives characterized by high
      levels of ecological uncertainty. Yet problems associated with its application
      are legendary, and many of the initiatives promoted as examples of adaptive
      management appear to lack essential characteristics of the approach. In this
      paper we propose explicit criteria for helping managers and decision makers to
      determine the appropriateness of either passive or active adaptive-management
      strategies as a response to ecological uncertainty in environmental management.
      Four categories of criteria--dealing with spatial and temporal scale, dimensions
      of uncertainty, the evaluation of costs and benefits, and institutional and
      stakeholder support--are defined and applied using hypothetical yet realistic
      case-study scenarios that illustrate a range of environmental management
      problems. We conclude that many of the issues facing adaptive management may have
      less to do with the approach itself than with the indiscriminate choice of
      contexts within which it is now applied.

PMID- 17205915
TI  - Heart rate variability in neurally mediated reflex syncope.
AB  - OBJECTIVE: The aim of this study was to investigate the heart rate variability
      (HRV) parameters in patients with neurally mediated reflex syncope. METHODS:
      Thirty-three patients (10 men, age range 16-50 years) who were scheduled to
      undergo head-upright tilt test (HUTT) with a typical history of vasovagal syncope
      (VVS) underwent 24-hour Holter monitoring in an attempt to study HRV parameters.
      Sixteen individuals without syncope and similar baseline characteristics made up
      the control group. RESULTS: Seventeen of the 33 syncopal patients showed HUTT
      positivity. All the time domain HRV parameters except the mean RR interval were
      higher in the HUTT (+) syncopal patients than in the negative responders.
      Although not statistically significant, the positive responders had higher NN50,
      pNN50, RMSSD and SDNNi values than the control group. HUTT (-) VVS patients had
      lower SDNN and SDANN values when compared with the control group. The other HRV
      parameters did not differ significantly between the HUTT (-) patients and the
      control group. CONCLUSION: Increased parasympathetic tonus as reflected by
      significantly higher HRV parameters is associated with a greater frequency of
      HUTT positivity in patients with syncope and no organic heart disease.

PMID- 17205916
TI  - Study of the correlation between blood lipid levels and the severity of coronary
      atherosclerosis in a Chinese population sample.
AB  - OBJECTIVE: To investigate the relationship between blood lipid levels with
      severity of coronary artery atherosclerosis in a Chinese population sample.
      METHODS AND RESULTS: According to coronary angiography results, 363 patients (287
      men and 76 women) with coronary artery atherosclerosis were divided into four
      groups: the single-vessel group (I, n = 125), the double-vessel group (II, n =
      113), the triple-vessel group (III, n = 107) and the multi-vessel group (IV, n =
      18). The severity of coronary artery atherosclerosis was quantified with a
      modified Gensini score on the basis of angiographic imaging. Serum triglycerides
      (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high
      density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol
      (non-HDL-C) were measured before angiography in all groups. Levels of serum TC,
      LDL-C and non-HDL-C of the II, III and IV group were significantly higher than
      those of the I group (4.78 +/- 0.82 mmol/L and 4.87 +/- 1.50 mmol/L and 4.73 +/-
      0.99 mmol/L vs. 4.38 +/- 0.93 mmol/L, 2.91 +/- 0.68 mmol/L and 2.74 +/- 1.23
      mmol/L and 2.64 +/- 0.84 mmol/L vs. 2.30 +/- 0.77 mmol/L, 3.58 +/- 0.75 mmol/L
      and 3.59 +/- 1.41 mmol/L and 3.43 +/- 0.94 mmol/L vs. 3.17 +/- 0.91 mmol/L; p <
      0.05); the mean levels of TC, LDL-C and non-HDL-C associated positively with the
      Gensini score. CONCLUSION: Serum lipid levels correlate positively with the
      severity of coronary artery atherosclerosis in a Chinese population sample.
      Patients with higher levels of serum TC, LDL-C and non-HDL-C have more severe
      coronary atherosclerosis, compared with those with low levels of serum TC, LDL-C
      and non-HDL-C.

PMID- 17205917
TI  - Cardiovascular risk factors in first-degree relatives of patients with premature
      coronary artery disease.
AB  - OBJECTIVE: The objective of this study was to evaluate the prevalence of coronary
      risk factors among Iranian first-degree relatives of patients with premature
      coronary artery disease (PCAD) and compare them with the general population.
      METHODS AND RESULTS: The study comprised 144 siblings and offspring (aged 25-64
      years) of patients with angiographically documented PCAD (< 55 years in men and <
      65 years in women). Body mass index, blood pressure and smoking were
      investigated. Fasting venous blood was analysed for lipids and fasting plasma
      glucose. The means of measured values and prevalence of risk factors were
      compared with the results obtained from the Tehran University Population
      Laboratory Study. Two or more atherosclerosis risk factors were found in 76% of
      men and 50.3% of women. Prevalence of smoking, obesity, hypertension and diabetes
      was 24.3%, 30%, 29.9% and 6.9%, respectively. Total cholesterol and LDL-C levels
      were higher than desirable in 36.8% and 15.3% of our subjects, respectively,
      14.6% had lower HDL-C values and 31.9% presented hypertriglyceridaemia. Overall,
      60.4% of cases revealed at least one of the lipid abnormalities. Compared with
      the Tehran University Population Laboratory Study men showed a higher prevalence
      of high LDL and triglyceride (TG) levels and obesity. High LDL-C and smoking were
      found to be more prevalent among women with a family history of premature CAD.
      CONCLUSIONS: The prevalence of coronary risk factors among first-degree relatives
      of patients with premature CAD is high, especially in men. Risk factor
      identification and modification should be considered in individuals with a
      positive family history of premature CAD.

PMID- 17205918
TI  - Tilt table testing in childhood: improved sensitivity by non-invasive
      haemodynamic monitoring devices?
AB  - OBJECTIVE: Tilt table testing represents a valuable diagnostic method in
      suspected neurally mediated syncope. As sympathovagal imbalance and impaired
      baroreceptor sensitivity (BRS) have been observed in these patients, both methods
      were used in this study to investigate whether a combination of these parameters
      would improve sensitivity and whether specific patterns of neurally mediated
      syncopes would correspond to characteristic trends in heart rate variability
      (HRV) and BRS. METHODS AND RESULTS: Fifty-one pts. (29 female, mean age 14.5 +/-
      3.9 y) with unexplained syncope and 15 control subjects (9 female, mean age 14.8
      +/- 3.0 y) were tested following a standard tilt table test protocol. Power
      spectral analysis (PSA) of HRV and BRS calculation were used additionally to beat
      to-beat blood pressure and ECG-monitoring. Twenty-three out of 51 pts. (45%)
      experienced a syncope after 18 +/- 10.2 min of tilting. In 2/23 patients (8.6%) a
      postural tachycardia syndrome (POTS), in 14/23 (60.8%) a neurally mediated
      syncope of mixed type, in 2/23 (8.6%) a vasodepressor syncope and in 5/23 (21.7%)
      a cardioinhibitory syncope with asystole were observed. PSA of HRV and BRS
      revealed a specificity, sensitivity, and positive and negative predictive values
      of the cut-off points in combination (LF/HF > or = 2.7 and BRS > or = 8) of
      93.3%, 65.2%, 93% and 39%, respectively. CONCLUSION: In this study population,
      BRS and PSA of HRV were able to improve sensitivity of tilt testing after
      unexplained syncope. Specific BRS or HRV patterns in different mechanisms of
      neurally mediated syncope could not be identified possibly due to the small
      sample size.

PMID- 17205919
TI  - Left ventricular hypertrophy in hypertensive obese women.
AB  - OBJECTIVE: Left ventricular hypertrophy (LVH) is an independent predictor of
      cardiovascular and general mortality. Both arterial hypertension and obesity
      cause changes in structure and function of the left ventricle. Given the rising
      global epidemic of obesity, it is likely that adverse health consequences of
      excess adiposity will escalate in the future. The aim of this investigation was
      to assess the relation and predictive value of obesity on the occurrence of left
      ventricular hypertrophy in hypertensive middle-aged women. METHODS AND RESULTS:
      Investigation was conducted on a sample of 64 middle-aged women, diagnosed with
      arterial hypertension and treated longer than 10 years in the absence of other
      chronic diseases or heart failure. Based on anthropometric parameters, 14 women
      (21.9%) had a body mass index (BMI) within the normal range, 17 (26.6%) were
      overweight, and 33 (52.5%) were obese. Left ventricular hypertrophy was assessed
      by electrocardiographic and echocardiographic criteria. The influence of
      anthropometric parameters on left ventricular hypertrophy and patterns in left
      ventricular geometry was assessed using multivariate regression analyses. The
      prevalence of LV hypertrophy was 7.1% among normal-weight hypertensive women,
      41.2% among overweight and 66.7% among obese women. Compared to normal-weight
      women, overweight and obese hypertensive subjects had higher mean values of all
      ECG and echo parameters. The strong correlation between anthropometric and left
      ventricular parameters was observed. Multivariate analysis showed that percent of
      body fat (OR = 1.226; 95% CI 1.011-1.486) was the only independent predictor of
      left ventricular hypertrophy. Being overweight was identified as predictor for
      the development of eccentric LV hypertrophy (OR = 31.824; 95% CI 1.225-826.850),
      and for concentric left ventricular remodelling (OR = 20.755; 95% CI 1.119
      385.029). CONCLUSIONS: Heart abnormalities occurring in arterial hypertension in
      conjunction with overweight/obesity include left ventricular hypertrophy and
      structural changes in the left ventricle. These findings support weight control
      and the regulation of blood pressure for the prevention of left heart
      abnormalities.

PMID- 17205920
TI  - Role of the ubiquitin-proteasome system in carotid plaque instability in diabetic
      patients.
AB  - In order to define the role of the ubiquitin-proteasome system in atherosclerotic
      plaque rupture in patients with type 2 diabetes mellitus (T2DM), we evaluated the
      amount of this system, of the main inflammatory cells, of the collagen content
      and some indexes indicative of oxidative stress in the carotid plaques of both
      diabetic and non-diabetic asymptomatic patients. Plaques were obtained from 31
      type 2 diabetic and 27 non-diabetic patients undergoing endoterectomy. Both were
      examined for macrophages, T-lymphocytes, ubiquitin/proteasome 20S activity, NFkB,
      IkB-b, nitrotyrosine, matrix metalloproteinase-9 (MMP-9) and collagen. Diabetic
      plaques had more macrophages,T-lymphocytes, inflammatory cells (HLA-DR),
      ubiquitin/proteasome, NFkB, nitrotyrosine, MMP-9 and lower collagen content and
      IkB-b levels, in comparison with non-diabetic plaques. These findings indicate
      that in diabetic patients, ubiquitin/proteasome overactivity is associated with
      enhanced inflammatory activity induced by diabetic oxidative stress. This induces
      the NFkB release into the nucleus which, in turn, is responsible for the
      expression of inflammatory cytokines causing plaque rupture.

PMID- 17205921
TI  - Cariporide attenuates myocardial ischaemia, reperfusion injury and apoptosis in
      isolated rat hearts.
AB  - OBJECTIVE: Inhibition of Na+/H+ exchanger (NHE) may protect the ischaemic
      reperfused myocardium by attenuating sodium overload. This study investigated the
      time-dependent beneficial effect of the NHEI inhibitor cariporide and the effect
      on early apoptosis in a rat model of ischaemia and reperfusion. METHODS AND
      RESULTS: The hearts of rats were perfused in a Langendorff apparatus. In the
      first part of the experiment, rats were divided into four groups: I/R (cariporide
      was not given), HOE-Pr+I/R (cariporide was given 15 min before ischaemia), HOE
      Is+I/R (cariporide was given shortly before ischaemia), HOE-Re+I/R (cariporide
      was given during reperfusion). The left ventricular systolic pressure (LVSP), the
      left ventricular end-diastolic pressure (LVEDP), arrhythmia, coronary flow and
      myocardial enzymes were measured. In the second part of the experiment, hearts
      were bathed in the presence or absence of cariporide before ischaemia. Terminal
      deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling
      (TUNEL) assays were used to quantify apoptotic cells. Improvement of recovery
      from ischaemia, defined as increased LVSP, decreased LVEDP, improvement in
      arrhythmia score, CK-MB and LDH was more significant in the HOE-Pr+I/R group than
      in the I/R group. Furthermore, cariporide given during ischaemia caused
      intermediate improvement of ischaemic recovery, while there was no difference
      between HOE-Re+I/R and I/R hearts. The number of apoptotic cells after ischaemia
      and reperfusion was 51.8 +/- 15.2 per 1000 cardiomyocytes compared to 11.5 +/-
      5.7 (p < 0.05) in hearts pretreated before ischaemia with cariporide.
      CONCLUSIONS: In conclusion, cariporide decreases the degree of impaired cardiac
      recovery and early apoptosis after ischaemia/reperfusion injury. The
      cardioprotective effects of cariporide are more pronounced when the drug is given
      before ischaemia.

PMID- 17205922
TI  - Amniotic fluid embolism: a rare cause of acute left-sided heart failure.
AB  - STUDY DESIGN AND SETTING: Two case reports, University Hospital of Antwerp,
      tertiary referral hospital of the University of Antwerp, Edegem, Belgium. METHODS
      AND RESULTS: Two women were transferred to our hospital because of acute
      cardiorespiratory failure due to amniotic fluid embolism during the peripartal
      period. Both required intensive supportive treatment and invasive monitoring.
      Haemodynamic data revealed primary left ventricular failure confirming the
      clinical picture of cardiogenic pulmonary oedema. Review of the literature
      provides data that do not support obstruction of the pulmonary vasculature by
      amniotic fluid as the only primary pathophysiological event. However, despite
      several case reports stressing left ventricular failure as the dominant clinical
      event, pathophysiological mechanisms are merely speculative. CONCLUSIONS: The
      diagnosis of amniotic fluid embolism remains a clinical challenge, but can be
      supported by the presence of amniotic cells in the pulmonary artery, aspirated
      through a pulmonary artery catheter. The treatment is still not causative but
      supportive. An overview of cases in the literature with predominant left heart
      failure during amniotic fluid embolism is given.

PMID- 17205923
TI  - The sick doctor: the sprayer sprayed.
AB  - "A physician does not need to have had a disease to know all its components, but
      it sharpens the perception ... one acquires a deeper understanding of the
      difference that exists between giving and receiving". Marcel Thibault, 2004.

PMID- 17205924
TI  - Echocardiographically suspected hypertrabeculation/noncompaction confirmed by
      magnetic resonance imaging in metabolic myopathy.

PMID- 17205925
TI  - Celiprolol-induced lupus-like syndrome.
AB  - Systemic lupus erythematosus can be idiopathic or drug-induced. Although a number
      of beta-blockers have been reported to induce a lupus-like syndrome, to the best
      of our knowledge, no such case has been described following celiprolol therapy.
      We diagnosed a lupus-like syndrome in a 67-year-old female patient who developed
      febrile polyarthritis, percarditis, antinuclear and anti-histone antibodies after
      taking celiprolol for 2 years. Despite drug withdrawal, prolonged corticotherapy
      was needed to obtain clinical and biological remission.

PMID- 17205926
TI  - Unruptured sinus of Valsalva aneurysm presenting as acute coronary syndrome.
AB  - Sinus of Valsalva aneurysm is an infrequent cardiac anomaly. In the United
      States, it accounts for only 0.15 to 1.5% of all cardiopulmonary bypass
      procedures. Sinus of Valsalva aneurysms can be acquired, secondary to infectious,
      degenerative or traumatic processes. This paper describes the case report of an
      81-year-old woman, with an unruptured aneurysm of the right Valsalva sinus, who
      was admitted to the emergency department with a history of chest pain. After
      surgical repair of the sinus ofValsalva aneurysm, the prognosis is usually good,
      and the risk of recurrence is rare.

PMID- 17205927
TI  - Auto-intoxication with flecainide and quinapril: ECG-changes, symptoms and
      treatment.
AB  - Flecainide acetate is a sodium channel blocker and a class Ic antiarrhythmic
      agent with potential life-threatening proarrhythmic and cardioinhibitory
      properties when taken in overdose. Quinapril is an angiotensin-converting enzyme
      inhibitor (ACE-inhibitor) and overdose can lead to prolonged hypotension and,
      less frequently, transient renal impairment. We describe the first published case
      of intoxication with both drugs. The patient developed a broad-QRS-tachycardia
      and severe hypotension. Treatment with volume expansion, hypertonic sodium
      bicarbonate, inotropic support with norepinephrine and insertion of an intra
      aortic balloon pump led to complete recovery after 72 hours. We assume that the
      clinical picture was mainly dictated by flecainide intoxication. Relevant
      literature data are discussed.

PMID- 17205928
TI  - Mitral valve thrombosis and infective endocarditis in a patient with prothrombin
      mutation.
AB  - This report deals with a 25-year-old female patient, who was admitted to a
      medical centre with complaints of fatigue and arthralgia. A non-homogeneous mass
      originating from the posterior papillary muscle and reaching the posterior and
      anterior cusps of the mitral valve was evident on the patient's echocardiogram.
      Her intractable fever, despite adequate antibiotic therapy, led us to consult
      with the cardiac surgeons. A mitral valve replacement was performed on the 8th
      day of admission. The pathological examination of the mitral valve and the
      vegetative lesion revealed the presence of organized thrombus and infective
      endocarditis. The patient had a history of oral contraceptive use for one year
      and at genetic examination we detected a heterozygous prothrombin mutation
      (G20210A). The association of infective endocarditis with native mitral valvular
      thrombosis in a case with prothrombin mutation and history of oral contraceptive
      use encouraged us to share our experience with our colleagues.

PMID- 17205929
TI  - [Agranulocytosis in a patient treated with metamizole and clopidogrel].

PMID- 17205930
TI  - [What is your diagnosis? Tongue diseases].

PMID- 17205931
TI  - [Cardiovascular prediction rules: problems for application in practice results of
      a workshop].
AB  - Guidelines for primary prevention of cardiovascular disease recommend a
      management based on global cardiovascular risk calculated with prediction rules.
      While cardiovascular prediction rules are applied as a tool to estimate risk,
      Guidelines describe which consequences to be drawn based on this risk
      information. We performed a workshop to discuss open questions for application of
      prediction rules in primary care. Technical aspects may not be a problem,
      however, additional barriers for application in daily routine exist. First,
      accuracy of risk estimation is unclear for some of the prediction rules. Second,
      risk factors, which are intuitively relevant (like obesity), are lacking in most
      of the prediction rules. Third, differences between guidelines and prediction
      rules are sometimes not clear for the general physician. In this article we want
      to answer the most important questions, which have been discussed during the
      workshop.

PMID- 17205932
TI  - [Treatment of acute myocardial infarction: a matter of time].

PMID- 17205933
TI  - [Comment on the case: "When life benefit becomes a problem"].

PMID- 17205934
TI  - [A 81-year-old patient with physiotherapy-resistant upper limb tenderness].
AB  - A 81-year-old patient with a six month history of upper extremity tenderness,
      most likely due to an atypical presentation of a polymyalgia rheumatica,
      responded well to a course of systemic steroids. A good clinical assessment is of
      primary importance to distinguish polymyalgia rheumatica from giant cell
      arteritis and other possible differential diagnoses, and constitutes the basis of
      a controlled therapy with steroids.

PMID- 17205935
TI  - [CME-ECG 14. Broad complex tachycardia].

PMID- 17205936
TI  - [Varicella: previously healthy children sometimes develop complications].
AB  - Three healthy boys, 3.5, 5 and 1.5 years of age, were admitted to hospital with a
      severe bacterial skin infection, cerebellar ataxia, and pneumonia, respectively,
      one week after the onset of varicella. They recovered completely after treatment.
      Studies in Europe report complications from varicella in 2.5% of healthy
      children. Most of these are neurological complications and secondary bacterial
      infections of skin and soft tissue. Last year, a European consensus was published
      that recommended that all healthy children be vaccinated against chickenpox. In
      The Netherlands, routine varicella zoster virus (VZV) vaccination has not (yet)
      been implemented. We propose a new discussion on the possible inclusion of VZV
      vaccination in the national vaccination programme.

PMID- 17205937
TI  - [Chickenpox: sufficient reasons for the introduction of vaccination].
AB  - The incidence of chickenpox and its complications is high enough to favour
      introducing varicella vaccination into the Dutch immunisation programme for
      children, although current Dutch figures may even underestimate the incidence.
      Safe and effective MMRV vaccines, in which varicella (V) vaccine is combined with
      measles, mumps and rubella (MMR), could well replace the MMR vaccine used at
      present. MMRV vaccines should be administered subcutaneously in two doses. Ten
      years after the introduction of varicella vaccination in the United States of
      America, the incidence of complications has decreased impressively. An effect on
      the incidence of herpes zoster has not (yet) been seen.

PMID- 17205938
TI  - [Limited possibilities for the evidence-based treatment and prevention of
      postherpetic neuralgia].
AB  - Postherpetic neuralgia is a disorder that occurs frequently in the elderly. As
      the effect of the treatment of postherpetic neuralgia is often disappointing,
      studies have focussed on the prevention of this complaint. A commonly used
      preventive intervention is the administration ofa single epidural injection of a
      local anaesthetic and a corticosteroid, combined with oral antiviral agents and
      analgesics. In a large, multicentre, randomised controlled trial, the
      investigators found that the single injection of a corticosteroid and a local
      anaesthetic had no added value in the prevention of long-term postherpetic
      neuralgia.

PMID- 17205939
TI  - [Treatment of testicular cancer clinical stage I: watchful waiting, radiotherapy,
      chemotherapy or surgical intervention].
AB  - Micrometastasis in the retroperitoneal lymph nodes is seen in 20% of patients
      with a seminoma in clinical stage I and in 30% of patients with a nonseminoma in
      clinical stage I. It is not possible to detect micrometastases. Nearly all
      patients recover from the illness irrespective of the treatment choice. This is
      based on the patient's wish, the doctor's preference, local expertise and risk
      factors for dissemination. In the case of a seminoma, treatment consists of
      regular checks ('watchful waiting'), radiotherapy or chemotherapy. In the case of
      a non-seminoma in clinical stage I without vascular impingement the risk of
      micrometastases in the retroperitoneal nodes is 15%. Standard treatment consists
      of watchful waiting. The options 'retroperitoneal lymph node dissection with, in
      the case of positive nodes, chemotherapy' and 'primary chemotherapy' result in
      more excessive treatment, but less uncertainty in patients. In the case of a non
      seminoma in clinical stage I with vascular impingement, the risk of
      micrometastases is 50%. Standard treatment in this case consists of watchful
      waiting or retroperitoneal lymph node dissection with chemotherapy, if necessary,
      in case of positive lymph nodes. Another option is primary chemotherapy.

PMID- 17205940
TI  - [Putative effects of doping in cycling].
AB  - After recent scandals in cycling involving doping, it has been asserted that top
      level cycling is impossible without pharmacological support. An important
      prerequisite for successfully completing the Tour de France is maintaining energy
      balance. To compensate for the daily caloric expenditure of 23-25 MJ,
      conventional food must be supplemented with liquid food. Quick administration of
      liquid carbohydrates is essential for optimal recovery of glycogen stores in the
      liver and skeletal muscle. Androgenic anabolic steroids are a frequently used
      form of doping. In endurance sports, these drugs have not been shown to affect
      endurance performance, and there is little evidence to suggest that they enhance
      recovery. Although epoetin use can increase maximal oxygen uptake, its effects on
      maximal power output are less pronounced than what is generally assumed. A
      relationship between haemoglobin concentration and sport performance has not been
      proved. It has been found that growth hormone rather has a negative than a
      positive influence on the sport performance. The doping problem is due in part to
      superstition, hearsay and insufficient knowledge among the athlete's support
      personnel, which frequently leads to medical malpractice in sport. Education and
      quality control for sport professionals, including sports physicians, may help to
      control the doping problem.

PMID- 17205941
TI  - [New drugs; ivabradine].
AB  - Ivabradine lowers the heart rate by inhibiting the cardiac pacemaker current that
      is responsible for diastolic depolarisation. The most important side effect is
      the appearance of light flashes (phosphenes). The agent can be used in patients
      with angina pectoris when beta-blockers are insufficiently effective, provided
      that the heart rate is at least 60 beats per minute at the beginning of the
      treatment.

PMID- 17205942
TI  - [Diagnostic image (302). A neonate with a knot in the umbilical cord].
AB  - After the delivery of a healthy boy, the umbilical cord showed a figure of eight
      stopper.

PMID- 17205943
TI  - [Treatment of patients with herpes zoster by epidural injection of steroids and
      local anaesthetics: less pain after 1 month, but no effect on long-term
      postherpetic neuralgia--a randomised trial].
AB  - OBJECTIVE: To assess the effectiveness of a single epidural injection of steroids
      and local anaesthetics, as a supplement to the standard treatment, for the
      prevention ofpostherpetic neuralgia in older patients with herpes zoster. DESIGN:
      Open randomised trial. METHOD: In the period September 2001-February 2004, 598
      patients, aged > 50 years, with acute herpes zoster (rash for < 7 days) below
      dermatome C6, were randomly assigned to receive either standard therapy (oral
      antiviral agents and analgesics) alone or standard therapy plus an additional
      single epidural injection of 80 mg methylprednisolone and 10 mg bupivacaine. The
      primary endpoint was the proportion of patients with zoster-associated pain one
      month after inclusion. The presence and severity of zoster-associated pain at
      other time points were secondary endpoints. RESULTS: At one month, pain was
      reported by 137 (48%) patients in the injection group versus 164 (58%) in the
      control group (relative risk; RR: 0.83; 95% CI: 0.71-0.97; p = 0.02). After three
      months, these values were 58 (21%) and 63 (24%), respectively (RR: 0.89; 95% CI:
      0.65-1-21; p = 0.47), and at 6 months: 39 (15%) and 44 (17%) (RR: 0.85; 95% CI:
      0.57-1-13; p = 0.43). No subgroups were detectable in which the relative risk for
      pain at one month after inclusion substantially differed from the overall
      estimate. At one month, the median severity of pain in the injection group was 2
      (on a 100-points scale) versus 6 in the control group (p = 0.02). At later follow
      up, there was no longer any statistically significant difference in the severity
      of pain between the two groups. No patient had major adverse events related to
      the epidural injection. CONCLUSION: A single epidural injection of steroids and
      local anaesthetics in the acute phase of herpes zoster resulted in a modest
      decrease in zoster-associated pain in the first month. This treatment did not,
      however, prevent long-term postherpetic neuralgia.

PMID- 17205944
TI  - [Three children with recurrent meningitis as the result of an anatomical defect].
AB  - Three children, a 12-year-old girl, a 5-year-old boy and a 5-year-old girl, were
      referred with recurrent episodes of meningitis. After an immunological defect had
      been ruled out early in the diagnostic work-up, the cause appeared to be an
      anatomical defect. After surgical treatment, no further meningitis occurred.
      Recurrent meningitis in children is rare. Anatomical defects, congenital or
      acquired, in the otorhinolaryngological area are the main cause. Conscientious
      history taking, careful physical examination and imaging using high-definition
      cranial computed tomography are important in establishing the diagnosis. In order
      to minimise the risk of another episode of meningitis, the otorhinolaryngologist
      should be consulted immediately in the diagnostic and therapeutic process and
      this process should be completed as soon as possible.

PMID- 17205945
TI  - [Sympathomimetic syndrome caused by autointoxication with methylphenidate].
AB  - A 31-year-old man claimed that he had ingested more than 100 tablets of
      methylphenidate (10 mg), 20 tablets ofibuprofen (400 mg) and 2 bottles of wine.
      At admission, signs of sympathomimetic syndrome were observed, including
      agitation, hallucinations, mydriasis and sinus tachycardia. The patient was
      treated with activated charcoal and an oral laxative. Given the possibly lethal
      dose of methylphenidate, the patient was admitted to the intensive care unit for
      observation. He made a full recovery and was discharged 36 hours after admission.
      Toxicological analysis indicated a plasma-ethanol concentration of 0.27% and a
      maximum serum-methylphenidate concentration of 176 microg/l (therapeutic range: 5
      40 microg/l). The active metabolite ethylphenidate was also present at toxic
      concentrations. Treatment of potentially lethal methylphenidate poisoning
      includes prevention of absorption, careful observation and support of vital
      functions as necessary.

PMID- 17205946
TI  - [The combination of acetylsalicylic acid and dipyridamole is more effective in
      secondary prevention following transient ischaemic attack or cerebral infarction:
      the debate is closed].

PMID- 17205947
TI  - [The combination of acetylsalicylic acid and dipyridamole is more effective in
      secondary prevention following transient ischaemic attack or cerebral infarction:
      the debate is closed].

PMID- 17205948
TI  - Comparison of interocclusal contacts registered intraorally and after a remount
      procedure in complete denture patients.
AB  - Prosthodontists recommend a remount procedure for identification and correction
      of occlusal errors in complete dentures rather than the more common practice of
      placing articulating paper intra-orally, followed by 'spot-grinding' at the chair
      side. There is no evidence to support this recommendation. The aim of this study
      was to compare the number and distribution of occlusal markings obtained using a
      remount procedure with those achieved using articulating paper intra-orally. 147
      edentulous subjects with newly constructed complete dentures participated. In all
      cases the remount method produced a significantly lower number of occlusal
      contacts compared with articulating paper used intra-orally (p<0.001). The
      distribution of occlusal markings was also different between the remount and
      intra-oral methods. These results suggest that, for complete dentures,
      articulating paper used intra-orally is inaccurate compared with a remount
      procedure.

PMID- 17205949
TI  - The effect of preparation height and taper on cement lute stress: a three
      dimensional finite element analysis.
AB  - Three dimensional finite element models of an upper second premolar and molar
      with full veneer gold crown preparations were developed from extracted samples.
      The cement lute width was kept constant at 40 microm, but the height and
      preparation taper were varied. For both models the preparation height was either
      1.5 mm (short preparation) or 3 mm (long preparation). The preparation taper was
      either 10 degree or 30 degree, giving a total of eight models. Each model was
      loaded with a 10 N horizontal load, a 10 N vertical load or a 10 N load
      distributed across the occlusal surface. The maximum shear stress and the maximum
      Von Mises' stress in the cement lute of each model were recorded. For the
      premolar, the maximum shear stresses ranged from 0.3-5.43 MPa and the maximum Von
      Mises' stress ranged from 1.44-14.98 MPa. For the molar, the maximum shear
      stresses ranged from 0.15-5.22 MPa and the maximum Von Mises' stress ranged from
      0.3 7-15.02 MPa. The stress fields were consistently higher in the premolar with
      a 30 degree preparation taper compared to the 10 degree taper. The attainment of
      a cavity taper of 100 is still important to minimise stress in the cement lute
      and is particularly important in teeth with a lower preparation surface area such
      as a premolar

PMID- 17205950
TI  - Partial- or full-mouth examination assessing the dental and prosthetic status
      among elderly individuals.
AB  - The aim of this study was to determine whether half-mouth examinations accurately
      reflect the dental and prosthetic status of the entire mouth. Samples of 1,830
      adults aged 55- 79 years were examined. The rate of agreement between half- and
      full-mouth examinations was estimated using weighted and unweighted Kappa values
      comparing findings of each tooth bilaterally. A power analysis was performed to
      estimate the number of subjects representing complete dental recordings within a
      certain power. Subjects showed unweighted Kappa values from 0.34-0.96. Weighted
      Kappa values ranged from 0. 74-0.99. A power analysis for unweighted Kappa scores
      computed that.findings from 122-335 individuals were necessary to equal the
      results obtained using complete dental recordings.

PMID- 17205951
TI  - An in-vitro investigation of the effect of a water additive and a new acidic
      primer on the tensile bond strength of composite resin to human enamel and
      dentine.
AB  - The aim of this study was to investigate the effect of a water additive on the
      bond strength of a composite restorative material to enamel and dentine which
      have undergone a range of surface treatments regimes. Human enamel and dentine
      specimens were prepared and divided into 3 surface treatment groups. Composite
      resin restorative material was bonded to the surface prepared enamel and dentine
      specimens. The tensile bond strength of the composite resin was measured using a
      Lloyd's testing machine. The tensile bond strength of composite resin to etched
      enamel surfaces using a standard etch technique was significantly greater than
      that to dentine (p < 0.05). For those specimens subjected to the addition of the
      water additive 'Alpron' the bond strength to the enamel was still significantly
      greater than to the dentine (p< 0.005). The addition of 'Alpron' to the water
      significantly improved the bond strength of composite to enamel and dentine when
      etched and placed with 'Prime&BondNT' (p < 0.05). There was no significant
      difference in bond strength of enamel and dentine specimens bonded using Xeno III
      (p> 0.05). However, the bond strength of dentine specimens bonded with Xeno III
      was significantly greater than other dentine specimens bonded with Prime&BondNT
      (p< 0.05). For those groups of specimens which included the water additive
      'Alpron' in the regime, the tensile bond strength of the composite resin
      restorative material to enamel and dentine was greater than for those non water
      additive groups. The tensile bond strength of composite resin bonded to enamel
      surfaces prepared with 'Alpron' was significantly higher than that bonded to
      dentine surfaces.

PMID- 17205952
TI  - A radiographic review of bone levels around Calcitek dental implants supporting
      mandibular over-dentures. Preliminary results at 3 to 6 years.
AB  - This retrospective study aimed to measure marginal bone resorption around
      cylindrical hydroxyapatite-coated implants retaining mandibular overdentures and
      compares this between two- and four- implant supported overdentures. Twenty three
      edentulous patients received 66 implants in their anterior mandible and were
      restored with overdentures. Panoramic radiographs one week post-operatively and
      at last recall were compared and marginal bone loss calculated. The mean recall
      interval was 51.22 months. The mean cumulative bone loss was 1.08 mm and the mean
      annual bone loss 0.263 mm. There was no significant difference between two- and
      four- implant overdentures. The results were comparable with other reports.

PMID- 17205953
TI  - Dental technicians' experiences with all-ceramic extra-coronal restorations.
AB  - The aim of this study was to identify the dental technicians' experiences with
      extra-coronal all-ceramic restorations. A questionnaire was mailed to all
      laboratories registered in The Norwegian Association of Dental Laboratory Owners
      (n=186). The response was 149 (80%). All-ceramic restorations were produced by 93
      (62%) of the responding laboratories. A few of these (1 7%) produced the majority
      (67%) of the restorations. The dental technicians reported low rates of remakes
      (median 2%) for all-ceramic restorations. The low production and the limited
      number of laboratories that perform this work show that there is room for
      extended training and more expertise in this field.

PMID- 17205954
TI  - Relationship between personality and satisfaction with the dentition in tooth
      wear patients.
AB  - This study was undertaken to identify whether personality traits had any
      relationship with patients' satisfaction with their dentition in tooth wear
      cases. One hundred tooth wear patients and one hundred controls were recruited
      into the study. A Dental Impact on Daily Living questionnaire was used to assess
      impact of tooth wear on day to day life and satisfaction with the dentition. An
      ordinal scale was used to assess tooth wear severity in tooth wear patients. The
      NEO Five Factor inventory was used to assess personal profiles. Tooth wear
      patients were less satisfied with their dentition, had higher Neuroticism, lower
      Extraversion, and higher Openness than the controls.

PMID- 17205955
TI  - Effectiveness of a self-adhesive resin luting system on fracture resistance of
      teeth restored with dentin-bonded crowns.
AB  - Laboratory studies have demonstrated satisfactory fracture resistance of all
      ceramic crowns placed using a conventional resin-composite luting material and a
      dentine bonding system. This study investigated the fracture resistance of teeth
      restored with dentine-bonded ceramic crowns luted with a self-etching luting
      material. Standardized preparations were carried out on two groups of ten sound,
      unrestored, maxillary premolar teeth. Ceramic crowns were constructed, their
      internal surfaces etched and placed using two luting system combinations.
      Compressive fracture resistance was determined for each group using a Universal
      Testing Machine. Mean compressive fracture resistance of 890 (222) N and 760
      (271) N were recorded for the RelyX Unicem Aplicap and Mirage groups,
      respectively. There was no significant difference in the mean compressive
      fracture resistance of the restored teeth in both groups (P<0.05). The failure
      modes were different for each cements with more severe (Mode V)failures
      associated with the Mirage group compared with the consistent Mode II failures
      associated with RelyX Unicem Aplicap. We conclude that the fracture resistance of
      dentine-bonded crowns luted with a self-adhesive resin-based luting material was
      no different from that of a conventional resin-based luting system. The fracture
      resistance of dentine-bonded ceramic crowns may be clinically satisfactory when a
      self-adhesive resin-based luting material is utilised.

PMID- 17205956
TI  - Brief report: testing the factorial invariance of the CBCL Somatic Complaints
      scale as a measure of internalizing symptoms for children with and without
      chronic illness.
AB  - OBJECTIVE: To examine the factorial invariance of the Somatic Complaints subscale
      of the Child Behavior Checklist as a measure of Internalizing Behavior Problems
      across a sample of children with and without spina bifida. METHODS: Multisample
      confirmatory factor analysis was used to compare mother and father report on the
      Somatic Complaints subscale across a sample of children with spina bifida and a
      matched comparison sample of able-bodied children ages 8 through 11 years (N = 68
      for mother report in each group; N = 54 for father report in the spina bifida
      group and 53 for the able-bodied group). RESULTS: Although there were no
      significant between-group differences in the magnitude of factor loadings,
      significantly more variance in scores on the Somatic Complaints scale was
      unrelated to Internalizing Behavior Problems for the spina bifida group, compared
      to the able-bodied group. There were no between-group differences when father
      data were analyzed, but the latent variable of Internalizing Behavior Problems
      explained little variance in the Somatic Complaints scale for either group.
      CONCLUSIONS: Maternal report of Somatic Complaints on the CBCL does not appear to
      measure Internalizing Behavior Problems in the same manner across groups of
      children with and without spina bifida. This suggests that the Somatic Complaints
      subscale should be interpreted with caution when measuring Internalizing Behavior
      Problems within this population.

PMID- 17205957
TI  - Specific changes in plasma concentrations of matrix metalloproteinase-2 and -9,
      TIMP-1 and TGF-beta1 in patients with distinct types of primary
      glomerulonephritis.
AB  - BACKGROUND: Dysregulated renal expression of matrix metalloproteinases (MMPs),
      tissue inhibitors of MMPs (TIMP) and TGF-beta1 contribute to the development of
      tubulo-interstitial fibrosis characteristic of progressive forms of primary
      glomerulonephritis (GN). There is little information on the circulating levels of
      these proteins in human GNs. Here, we assessed whether different
      histopathological GN types could be associated with distinct plasma patterns of
      MMPs and regulatory proteins. METHODS: Protein levels of MMP-2, MMP-9, TGF-beta1
      and TIMP-1 were measured by ELISA in plasma from venous blood of 108 untreated
      patients with various types of primary GN defined by kidney biopsy, namely IgAN
      (n=63), membranous GN (MN, n=26), minimal change nephrotic syndrome (MCNS, n=12)
      and focal and segmental glomerular sclerosis (FSGS, n=7), and were compared with
      levels in 50 healthy subjects. Plasma samples were assayed for gelatinolytic
      activity (zymography). RESULTS: Zymography detected the proforms of MMP-2 and MMP
      9. Compared with controls, IgAN patients exhibited a significant, parallel
      decrease in plasma levels of MMP-2, MMP-9 and TGF-beta1. In MN patients,
      decreased MMP-9 level contrasted with a high MMP-2 level and a normal TGF-beta1
      level. In the MCNS/FSGS group, increased MMP-2 level contrasted with unchanged
      MMP-9 and decreased TGF-beta1 levels. Plasma concentration of TIMP-1 was elevated
      in all GN groups. There was no correlation between baseline MMP-2/MMP-9/TIMP
      1/TGF-beta1 levels and the degree of renal dysfunction or with progression toward
      ESRD. CONCLUSIONS: Plasma concentrations of MMP-2, MMP-9 and TGF-beta1
      significantly differed between the various histopathological types of primary
      GNs, thus suggesting the involvement of different underlying mechanisms in the
      regulation of glomerular and tubulointerstitial fibrosis in these renal diseases.

PMID- 17205958
TI  - ACE gene I/D polymorphism and the presence of renal failure or hypertension in
      autosomal dominant polycystic kidney disease (ADPKD).

PMID- 17205959
TI  - Vibrio vulnificus peritonitis after eating raw sea fish in a patient undergoing
      continuous ambulatory peritoneal dialysis (CAPD).

PMID- 17205960
TI  - Is there really good news about pandemic diabetic nephropathy?

PMID- 17205961
TI  - Microalbuminuria, but not cystatin C, is associated with carotid atherosclerosis
      in middle-aged adults.
AB  - BACKGROUND: Cystatin C, a marker of renal function, has been shown to be an
      independent predictor of cardiovascular disease (CVD) in older adults, but few
      data are available in middle-aged adults. Moreover, no study has compared
      cystatin C and microalbuminuria as risk factors for CVD outcomes in middle-aged
      adults, and it is not known whether cystatin C is related to an early stage of
      atherosclerosis. METHODS: We evaluated the relationships between serum
      creatinine, estimated glomerular filtration rate (GFR), serum cystatin C (all
      divided into tertiles), microalbuminuria and carotid atherosclerosis in a
      population-based random sample of 523 adults aged 35-64 years from the Seychelles
      (Indian Ocean). GFR was estimated using the modification of diet in renal disease
      (MDRD) equation. Intima-media thickness (IMT) was assessed by B-mode ultrasound.
      RESULTS: The mean age of the study sample was 52 years, and 55% were women.
      Carotid IMT was higher in participants with microalbuminuria (802 vs 732 microm,
      P<0.001) and was inversely associated with GFR tertiles (from 728 to 809 microm,
      P for trend=0.002). IMT was not associated with cystatin C or creatinine (P for
      trend=0.10 and 0.16, respectively). In multivariate analyses adjusted for
      cardiovascular risk factors, the association between microalbuminuria and IMT
      remained (P=0.047), while the association between GFR and IMT disappeared (P for
      trend=0.33). CONCLUSIONS: Microalbuminuria, but not cystatin C, is associated
      with carotid atherosclerosis beyond traditional cardiovascular risk factors among
      middle-aged adults. Cystatin C does not have a stronger relationship with carotid
      atherosclerosis in middle-aged adults than creatinine.

PMID- 17205962
TI  - Mineral metabolism parameters throughout chronic kidney disease stages 1-5-
      achievement of K/DOQI target ranges.
AB  - BACKGROUND: Dialysis Outcomes and Practice Patterns Study has shown that the
      proportion of haemodialysis patients with adequate mineral metabolism parameters
      according to the Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines is
      very low. The adequacy of such parameters in relation to the recommended ranges
      in patients with different chronic kidney disease (CKD) stages has not been
      reported. The objective of this study is to provide an in-depth description of
      mineral metabolism in the early stages of CKD in a European population, and to
      compare it with current recommendations for stages 3-5 (K/DOQI guidelines).
      METHODS: A total of 1836 patients were classified into stages 1-5 according to
      K/DOQI guidelines. The following clinical and biochemical data were recorded:
      age, gender, CKD aetiology, presence of diabetes, serum creatinine, creatinine
      clearance, serum phosphate, calcium, CaxP product and intact parathyroid hormone
      (PTH). RESULTS: A decrease in 1,25-dihydroxyvitamin D and an increase in PTH are
      the earliest mineral metabolism alterations in CKD, while serum calcium and
      phosphate are altered later in the course of CKD. The percentages of patients
      with serum levels within the recommended K/DOQI guidelines for stages 3, 4 and 5
      were as follows: serum calcium: 90.7, 85.6 and 55; serum phosphate: 90.9, 77.1
      and 70.3; iPTH 42.4, 24.6 and 46.8 and Ca x P product 99.9, 99.6 and 83.8,
      respectively. The percentages of patients who had all four parameters within the
      recommended ranges were 34.9, 18.4 and 21.6 for stages 3, 4 and 5, respectively.
      CONCLUSION: Mineral metabolism disturbances start early in the course of CKD. The
      first alterations to take place are a 1,25-dihydroxyvitamin D decrease, a 24 h
      urine phosphate decrease and a PTH elevation, which show significant level
      variation when the glomerular filtration rate falls below 60 ml/min. K/DOQI
      recommended levels for mineral metabolism parameters are difficult to accomplish,
      in particular for PTH levels.

PMID- 17205963
TI  - A leucine repeat in the carnosinase gene CNDP1 is associated with diabetic end
      stage renal disease in European Americans.
AB  - BACKGROUND: Four linkage analyses have identified a region on chromosome 18q22-23
      that appears to harbour a diabetic nephropathy (DN) susceptibility locus. A
      trinucleotide repeat sequence in exon 2 of the carnosinase gene (CNDP1) residing
      on 18q22.3 was subsequently associated with DN in European Caucasians and Arabs.
      METHODS: We evaluated the role of the CNDP1 5 leucine/5 leucine (5-5)
      polymorphism (CNDP1 Mannheim) in diabetic end-stage renal disease (ESRD)
      susceptibility in 858 European Americans: 294 with type 2 DN-associated ESRD (DN
      ESRD), 258 with diabetes mellitus (DM) lacking nephropathy and 306 healthy
      controls. RESULTS: Subjects with DM lacking nephropathy were significantly more
      likely to be homozygous for the 5-leucine repeat CNDP1 genotype (5-5), compared
      with those with DN-ESRD (P=0.02). Healthy controls were also more likely to be
      homozygous for the 5-5 genotype, compared with those with DN-ESRD (P=0.008). No
      significant difference in 5-5 genotype frequency was observed between healthy
      controls and DM cases without nephropathy (P=0.74). CONCLUSION: European
      Americans homozygous for the 5-5 leucine repeat polymorphism in the CNDP1 gene
      are at significantly reduced risk for developing diabetic ESRD. This replicates
      the CNDP1 gene association with DN that was initially detected in European
      Caucasians and in Arabs, and further demonstrates that the CNDP1 gene and
      carnosine pathway appear to play a role in susceptibility to DN.

PMID- 17205964
TI  - Significance of glomerular cell apoptosis in the resolution of acute post
      streptococcal glomerulonephritis.
AB  - BACKGROUND: Glomerular hypercellularity due to resident glomerular cell
      proliferation and leucocyte infiltration has been described in acute post
      streptococcal glomerulonephritis (APSGN). APSGN usually resolves without
      progression. However, the mechanism of resolution remains to be determined.
      METHODS: Renal biopsy tissues from 15 patients with APSGN (obtained 1-31 days
      after disease onset) and five control patients with minor glomerular abnormality
      were evaluated with respect to glomerular resolution. Apoptotic cells were
      assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labelling (TUNEL) as well as by immunostaining of single-stranded DNA (ssDNA).
      RESULTS: The number of glomerular cells was high in the early-phase of APSGN and
      decreased over time. No TUNEL+ glomerular cells were found in control subjects,
      whereas prominent glomerular TUNEL+ cells were observed in APSGN patients,
      particularly in the early phase of the disease. The number of glomerular TUNEL+
      cells decreased exponentially but was still prominent in renal tissue biopsied at
      31 days after disease onset. Double staining for ssDNA and glomerular cell
      markers showed that glomerular apoptotic cells were predominantly mesangium and
      endothelial cells, with some neutrophils and macrophages. CONCLUSIONS: These
      results suggest that apoptosis exists in the glomerulus in patients with APSGN
      from the early to the late stages of the disease and contributes to the
      resolution of glomerular hypercellularity.

PMID- 17205965
TI  - Complications of gallstone disease in kidney transplantation patients.
AB  - BACKGROUND: We studied the complications of gallstone disease in kidney
      transplantation patients and evaluated whether the screening and treatment of
      gallstones before acceptance to the kidney waiting list is relevant. METHODS:
      Complications of gallstone disease were evaluated in 1608 kidney transplantation
      patients on cyclosporine and long-term steroid treatment with median age 45.5
      years, transplanted between 1990 and 2000. To evaluate the prevalence of
      cholecystolithiasis after kidney transplantation an abdominal ultrasound
      examination was cross-sectionally performed to a subgroup of 304 patients and the
      results were correlated to their serum lipid values, changes in BMI and use of
      statins. RESULTS: Pre-transplant cholecystectomy due to cholecystolithiasis
      (prerequisite for acceptance to kidney waiting list) had been performed on 71
      (4%) of the patients. Thirty (15%) patients with diagnosed post-transplant
      gallstones and four without gallstones developed biliary complications. There
      were 25 cases of cholecystitis of which three resulted in gallbladder
      perforations. Seventeen patients (50%) with biliary complications required urgent
      surgery and one (3%) patient died of post-operative complications. In the
      subgroup of ultrasound examination patients (median 7 years post-transplant
      follow-up) 81% of the patients had no gallstones and 9% of the patients had
      gallstones had developed after transplantation. Patients with pre-transplant
      gallstones were older (P < 0.01) and patients with post-transplant gallstones
      gained the most weight during the follow-up. No differences in lipid values were
      found. CONCLUSION: In transplantation patients, the complications of gallstone
      disease may be severe. Screening and treatment of pre- and post-transplantation
      gallstone disease are recommended.

PMID- 17205966
TI  - Serum and cellular interleukin-6 in haemodialysis patients: relationship with
      energy expenditure.
AB  - BACKGROUND: Inflammation is a highly prevalent condition among end-stage renal
      disease (ESRD) patients and it has been implicated with several metabolic
      derangements. Considering the harmful effect of hypermetabolism on nutritional
      status and clinical outcomes of ESRD patients, we aimed to investigate the
      relationship between proinflammatory cytokine interleukin-6 (IL-6) and energy
      expenditure in this population. METHODS: This cross-sectional study enrolled 80
      adult haemodialysis patients for the evaluation of serum IL-6 and energy
      expenditure. The production of IL-6 by peripheral blood mononuclear cells (PBMCs)
      (spontaneous and endotoxin-stimulated production) was examined in a subgroup of
      30 haemodialysis patients and in 11 healthy control subjects. IL-6 was measured
      by immunoenzymatic assay. The resting energy expenditure was evaluated by means
      of indirect calorimetry. Body composition was assessed by bioelectrical impedance
      analysis and skinfold thicknesses. RESULTS: Serum IL-6 [6.3 (2.2-163.5) pg/ml]
      correlated positively with age (R = 0.26; P = 0.02) and C-reactive protein (R =
      0.31; P < 0.01). Resting energy expenditure correlated positively with lean body
      mass (R = 0.68; P < 0.001) and BMI (R = 0.44; P < 0.001), and negatively with
      Kt/V (R = -0.37; P < 0.01). In the multivariate analysis, controlling for age and
      lean body mass, serum IL-6 was positively associated with resting energy
      expenditure (n = 80; beta = 2.4; P = 0.01). The production of IL-6 by PBMCs did
      not reach statistically significant differences between patients and controls
      [spontaneous production 6541 (96-7739) pg/ml vs 3410 (50-7806) pg/ml,
      respectively; and stimulated production 6530 (579-7671) pg/ml vs 5304 (1527-7670)
      pg/ml, respectively]. IL-6 secreted by monocytes showed no association with
      either serum IL-6 or resting energy expenditure. CONCLUSION: Serum IL-6 was
      associated with an increase of energy expenditure in haemodialysis patients.

PMID- 17205967
TI  - Immunohistochemical comparison of a case of inherited distal renal tubular
      acidosis (with a unique AE1 mutation) with an acquired case secondary to
      autoimmune disease.

PMID- 17205968
TI  - The expression patterns of three class B genes in two distinctive whorls of
      petaloid tepals in Alstroemeria ligtu.
AB  - Alstroemeria (Liliales) has two layers of petaloid tepals, in which the often
      spotted narrow inner tepals can be distinguished easily from the wider outer
      tepals. In order to explore this floral morphology in Alstroemeria, we
      investigated the tepal morphology and the expression patterns of three class B
      genes, whose homologs in eudicots have been shown previously to be involved in
      petal and stamen development. The two DEF-like genes (AlsDEFa and AlsDEFb) and
      the one GLO-like gene (AlsGLO) of Alstroemeria ligtu were isolated by rapid
      amplification of cDNA ends (RACE). Northern hybridization, reverse transcription
      PCR (RT-PCR) and in situ hybridization analyses indicated that AlsDEFb and AlsGLO
      were expressed in whorls 1, 2 and 3 (outer tepals, inner tepals and stamens,
      respectively), whereas AlsDEFa expression was detected only in whorls 2 and 3.
      These results suggest that in A. ligtu, AlsDEFb and AlsGLO would participate in
      determining the organ identity of the two-layered petaloid tepals and stamens,
      which is in support of the modified ABC model. Additionally, the distinctive
      expression patterns of AlsDEFa and AlsDEFb might be related to morphological
      differences between the two-layered tepals.

PMID- 17205969
TI  - Ethylene promotes submergence-induced expression of OsABA8ox1, a gene that
      encodes ABA 8'-hydroxylase in rice.
AB  - A rapid decrease of the plant hormone ABA under submergence is thought to be a
      prerequisite for the enhanced elongation of submerged shoots of rice (Oryza
      sativa L.). Here, we report that the level of phaseic acid (PA), an oxidized form
      of ABA, increased with decreasing ABA level during submergence. The oxidation of
      ABA to PA is catalyzed by ABA 8'-hydroxylase, which is possibly encoded by three
      genes (OsABA8ox1, -2 and -3) in rice. The ABA 8'-hydroxylase activity was
      confirmed in microsomes from yeast expressing OsABA8ox1. OsABA8ox1-green
      fluorescent protein (GFP) fusion protein in onion cells was localized to the
      endoplasmic reticulum. The mRNA level of OsABA8ox1, but not the mRNA levels of
      other OsABA8ox genes, increased dramatically within 1 h after submergence. On the
      other hand, the mRNA levels of genes involved in ABA biosynthesis (OsZEP and
      OsNCEDs) decreased after 1-2 h of submergence. Treatment of aerobic seedlings
      with ethylene and its precursor, 1-aminocyclopropane-1-carboxylate (ACC), rapidly
      induced the expression of OsABA8ox1, but the ethylene treatment did not strongly
      affect the expression of ABA biosynthetic genes. Moreover, pre-treatment with 1
      methylcyclopropene (1-MCP), a potent inhibitor of ethylene action, partially
      suppressed induction of OsABA8ox1 expression under submergence. The ABA level was
      found to be negatively correlated with OsABA8ox1 expression under ACC or 1-MCP
      treatment. Together, these results indicate that the rapid decrease in ABA levels
      in submerged rice shoots is controlled partly by ethylene-induced expression of
      OsABA8ox1 and partly by ethylene-independent suppression of genes involved in the
      biosynthesis of ABA.

PMID- 17205970
TI  - Dissection of enhanced cell expansion processes in leaves triggered by a defect
      in cell proliferation, with reference to roles of endoreduplication.
AB  - Leaf development relies on cell proliferation, post-mitotic cell expansion and
      the coordination of these processes. In several Arabidopsis thaliana mutants
      impaired in cell proliferation, such as angustifolia3 (an3), leaf cells are
      larger than normal at their maturity. This phenomenon, which we call compensated
      cell enlargement, suggests the presence of such coordination in leaf development.
      To dissect genetically the cell expansion system(s) underlying this compensation
      seen in the an3 mutant, we isolated and utilized 10 extra-small sisters (xs)
      mutant lines that show decreased cell size but normal cell numbers in leaves. In
      the xs single mutants, the palisade cell sizes in mature leaves are about 20-50%
      smaller than those of wild-type cells. Phenotypes of the palisade cell sizes in
      all combinations of xs an3 double mutants fall into three classes. In the first
      class, the compensated cell enlargement was significantly suppressed. Conversely,
      in the second class, the defective cell expansion conferred by the xs mutations
      was significantly suppressed by the an3 mutation. The residual xs mutations had
      effects additive to those of the an3 mutation on cell expansion. The
      endopolyploidy levels in the first class of mutants were decreased, unaffected or
      increased, as compared with those in wild-type, suggesting that the abnormally
      enhanced cell expansion observed in an3 could be mediated, at least in part, by
      ploidy-independent mechanisms. Altogether, these results clearly showed that a
      defect in cell proliferation in leaf primordia enhances a part of the network
      that regulates cell expansion, which is required for normal leaf expansion.

PMID- 17205971
TI  - Individual differences in odor imaging ability reflect differences in olfactory
      and emotional perception.
AB  - We asked whether the large variability in odor imaging ability is underlain by
      interindividual differences in the processing of smells and emotion. Olfactory
      imaging ability, anhedonia level, and odor perception were measured in 40
      subjects, using the Vividness of Olfactory Imagery Questionnaire (VOIQ), the
      Physical Anhedonia Scale, and the European Test of Olfactory Capabilities. "Good"
      olfactory imagers, defined primarily on the basis of the VOIQ, rated pleasant
      smells as more familiar and had lower anhedonia scores than "bad" olfactory
      imagers. Based on self-reported measures, these results suggest that, like
      olfactory perception, the mental imagery of smells is related to emotion and
      that, beyond their differences in vividness, good and bad olfactory imagers
      differ in their experience of emotion and long-term memory of smells.

PMID- 17205972
TI  - The expression of Wiskott-Aldrich syndrome protein (WASP) is dependent on WASP
      interacting protein (WIP).
AB  - The Wiskott-Aldrich syndrome protein (WASP) is a key molecule for transduction of
      extracellular signals that induce a variety of critical biological events
      involving actin cytoskeleton rearrangement. Among the cellular partners of WASP,
      the Wiskott-Aldrich syndrome protein-interacting protein (WIP) has been
      speculated to play a critical role in the pathophysiology of Wiskott-Aldrich
      syndrome since WASP mutation hot spots map to the WIP-binding region. The notion
      that WIP promotes WASP function, however, conflicts with evidence that WIP
      inhibits WASP-mediated actin polymerization and IL-2 production and suggests a
      complex regulation of WASP function by WIP. Here we show that WASP gene transfer
      results in high WASP expression only when WIP is concomitantly expressed in K562
      cells. Furthermore, WIP-knockdown experiments demonstrated that T cells with
      reduced WIP expression show a concordant reduction of WASP levels. Mapping
      studies using WIP mutants showed that the minimal WIP region able to rescue WASP
      expression in WIP-knockdown cells was the WASP-binding domain. However,
      expression of such a minimal domain of WIP failed to rescue WASP-dependent,
      nuclear factor of activated T-cells-mediated IL-2 transcriptional activity. These
      results demonstrate that expression of WIP is necessary for functional WASP
      expression in human cells and provide a new paradigm for understanding the
      function of these two molecules.

PMID- 17205974
TI  - Empathy for pain and touch in the human somatosensory cortex.
AB  - Although feeling pain and touch has long been considered inherently private,
      recent neuroimaging and neurophysiological studies hint at the social
      implications of this experience. Here we used somatosensory-evoked potentials
      (SEPs) to investigate whether mere observation of painful and tactile stimuli
      delivered to a model would modulate neural activity in the somatic system of an
      onlooker. Viewing video clips showing pain and tactile stimuli delivered to
      others, respectively, increased and decreased the amplitude of the P45 SEP
      component that reflects the activity of the primary somatosensory cortex (S1).
      These modulations correlated with the intensity but not with the unpleasantness
      of the pain and touch ascribed to the model or the aversion induced in the
      onlooker by the video clips. Thus, modulation of S1 activity contingent upon
      observation of others' pain and touch may reflect the mapping of sensory
      qualities of observed painful and tactile stimuli. Results indicate that the S1
      is not only involved in the actual perception of pain and touch but also plays an
      important role in extracting somatic features from social interactions.

PMID- 17205975
TI  - Effects of prolonged exposure to perchlorate on thyroid and reproductive function
      in zebrafish.
AB  - The objectives of this study were to determine the effects of prolonged exposure
      to perchlorate on (1) thyroid status and reproductive performance of adult
      zebrafish (Danio rerio) and (2) F1 embryo survival and early larval development.
      Using a static-renewal procedure, mixed sex populations of adult zebrafish were
      exposed to 0, 10, and 100 mg/l nominal concentrations of waterborne perchlorate
      for 10 weeks. Thyroid histology was qualitatively assessed, and females and males
      were separated and further exposed to their respective treatments for six
      additional weeks. Eight females in each tank replicate (n = 3) were paired weekly
      with four males from the same respective treatment, and packed-egg (spawn) volume
      (PEV) was measured each of the last five weeks. At least once during weeks 14-16
      of exposure, other end points measured included fertilization rate, fertilized
      egg diameter, hatching rate, standard length, and craniofacial development of 4
      day-postfertilization larvae and thyroid hormone content of 3.5-h embryos and of
      exposed mothers. At 10 weeks of exposure, perchlorate at both concentrations
      caused thyroidal hypertrophy and colloid depletion. A marked reduction in PEV was
      observed toward the end of the 6-week spawning period, but fertilization and
      embryo hatching rates were unaffected. Fertilized egg diameter and larval length
      were increased by parental exposure to perchlorate. Larval head depth was
      unaffected but the forward protrusion of the lower jaw-associated cartilage
      complexes, Meckel's and ceratohyal, was decreased. Exposure to both
      concentrations of perchlorate inhibited whole-body thyroxine content in mothers
      and embryos, but triiodothyronine content was unchanged. In conclusion, prolonged
      exposure of adult zebrafish to perchlorate not only disrupts their thyroid
      endocrine system but also impairs reproduction and influences early F1
      development.

PMID- 17205976
TI  - In vitro toxicity of tetrabromobisphenol-A on cerebellar granule cells: cell
      death, free radical formation, calcium influx and extracellular glutamate.
AB  - Tetrabromobisphenol-A (TBBPA) is one of the worlds most widely used brominated
      flame retardant. The present study reports effects of TBBPA on primary cultures
      of cerebellar granule cells (CGC). Using the trypan blue exclusion assay, we show
      that TBBPA induces death of CGC at low micro molar concentrations. Cell death was
      reduced by the NMDA receptor antagonist MK-801 (3 microM), the antioxidant
      vitamin E (50 microM), and in calcium-free buffer. We further demonstrate that
      TBBPA's toxicity was accompanied by apoptosis-like nuclear shrinkage, chromatin
      condensation, and DNA fragmentation. Other hallmarks of apoptosis such as caspase
      activity were, however, absent, indicating an atypical form of apoptosis. TBBPA
      increased intracellular free calcium in a concentration-dependent manner. TBBPA
      also induced an increase in extracellular glutamate in a time-dependent manner.
      TBBPA gave a concentration-dependent increase information reactive oxygen species
      (ROS) of measured with 2,7-dichlorofluorescein diacetate. The ROS formation was
      inhibited by the extracellular signal-regulated protein kinase (ERK) inhibitor
      U0126 (10 microM), the tyrosine kinase inhibitor erbstatin-A (25 microM),
      eliminating calcium from the buffer and by the superoxide dismutase inhibitor
      diethyldithio-carbamic acid (DDC, 100 microM). Further analysis with Western blot
      confirmed phosphorylation of ERK1/2 after exposure to TBBPA. We found that TBBPA
      induces ROS formation, increases intracellular calcium, extracellular glutamate,
      and death of CGC in vitro at concentrations comparable to those of
      polychlorinated biphenyl. These findings implicate TBBPA as a predicted
      environmental toxin and bring out the importance of awareness of its hazardous
      effects.

PMID- 17205977
TI  - Chimpanzee, orangutan, mouse, and human cell cycle promoters exempt CCAAT boxes
      and CHR elements from interspecies differences.
AB  - Mechanisms regulating the cell division cycle are well conserved among all
      eukaryotes. Consistently many proteins regulating the cell cycle are functionally
      interchangeable between many organisms. Cell division control is regulated on
      different levels of which the transcriptional level appears to be particularly
      important for controlling synthesis of many cell cycle proteins. We had earlier
      described transcription factor-binding sites essential for regulating genes
      important for the transition from the G(2) phase to mitosis. A tandem repressor
      site named cell cycle-dependent element (CDE) and cell cycle genes homology
      region (CHR) are responsible for the correct expression during the cell cycle.
      Another feature of these G(2)/M-specific promoters is the activation through 2 or
      3 CCAAT boxes binding the transcription factor nuclear factor-Y (NF-Y). These
      major activating sites have to be spaced 32 or 33 bp apart to be fully
      functional. We were interested in looking at the evolutionary changes in
      regulatory elements and overall promoter structure of 3 well-characterized cell
      cycle genes. Here, we compare the DNA sequences and functional features of the
      cdc25C, cyclin B1, and cyclin B2 promoters from humans, mouse, chimpanzee, and
      orangutan. We find numerous differences in the nucleotide sequence between mouse
      and primate promoters. However, CHR and CCAAT boxes stand out in that they are
      perfectly conserved in all promoters tested. The CDE site contains nucleotide
      exchanges between mouse and primate promoters. Comparing sequences and functions
      of chimpanzee, orangutan, and human promoters, we observe a complete conservation
      in nucleotide sequence of the regulatory elements. Functional assays of the
      cyclin B1, cyclin B2, and cdc25C promoters yield moderate variations in activity
      and thereby a good conservation of function. Although we find nucleotide
      differences in cell cycle promoters between orangutan and humans of about 5%,
      there are never changes in any of the CCAAT boxes or CDE/CHR sites in the cyclin
      B1, cyclin B2, and cdc25C promoters. Furthermore, we describe the influence of
      the tumor suppressor p53 and the transcriptional activator NF-Y on regulation of
      the newly cloned primate promoters.

PMID- 17205978
TI  - Rapid and individual-specific glycoprofiling of the low abundance N-glycosylated
      protein tissue inhibitor of metalloproteinases-1.
AB  - A gel-based method for a mass spectrometric site-specific glycoanalysis was
      developed using a recombinant glycoprotein expressed in two different cell lines.
      Hydrophilic interaction liquid chromatography at nanoscale level was used to
      enrich for glycopeptides prior to MS. The glycoprofiling was performed using
      matrix-assisted laser desorption/ionization MS and MS/MS. The method proved to be
      fast and sensitive and furthermore yielded a comprehensive site-specific glycan
      analysis, allowing a differentiation of the glycoprofiles of the two sources of
      recombinant protein, both comprising N-glycans of a highly heterogeneous nature.
      To test the potential of the method, tissue inhibitor of metalloproteinases-1
      (TIMP-1), a secreted low abundance N-glycosylated protein and a cancer marker,
      was purified in an individual-specific manner from plasma of five healthy
      individuals using IgG depletion and immunoaffinity chromatography. The
      corresponding TIMP-1 glycoprofiles were determined to be highly similar,
      comprising mainly bi- and triantennary complex oligosaccharides. Additionally it
      was shown that platelet-derived TIMP-1 displayed a similar glycoprofile. This is
      the first study to investigate the glycosylation of naturally occurring human
      TIMP-1, and the high similarity of the glycoprofiles showed that individual
      specific glycosylation variations of TIMP-1 are minimal. In addition, the results
      showed that TIMP-1 derived from platelets and plasma is similarly glycosylated.
      This comprehensive and rapid glycoprofiling of a low abundance glycoprotein
      performed in an individual-specific manner allows for future studies of
      glycosylated biomarkers for person-specific detection of altered glycosylation
      and may thus allow early detection and monitoring of diseases.

PMID- 17205979
TI  - Lysine trimethylation of retinoic acid receptor-alpha: a novel means to regulate
      receptor function.
AB  - Retinoic acid receptors (RARs) belong to the nuclear receptor superfamily. The
      mechanism of ligand-dependent activation of RARs is well known. The effect of
      protein phosphorylation on the activity of RARs has also been demonstrated.
      However, it is unclear whether other types of modifications exist and if so
      whether they can affect the activity of RARs. In a mass spectrometric analysis of
      mouse RARalpha expressed in insect cells, we identified a trimethylation site on
      Lys(347) in the ligand binding domain. The modification site was verified in
      mammalian cells, and site-directed mutagenesis studies revealed the functionality
      of Lys(347) methylation in vivo. Constitutive negative mutants, mimicking
      hypomethylated RARalpha, were prepared by replacing methylated Lys(347) with
      either alanine or glutamine. A constitutive positive mutant partially mimicking
      the hypermethylated RARalpha was generated by replacing the methylated lysine
      residue with phenylalanine, a bulky hydrophobic amino acid, to introduce a site
      specific hydrophobicity similar to that contributed by lysine methylation.
      Studies of these mutants revealed that trimethylation of Lys(347) of RARalpha
      facilitated its interactions with cofactors p300/CREB-binding protein-associated
      factor and receptor-interacting protein 140 as well as its heterodimeric partner
      retinoid X receptor, suggesting that site-specific hydrophobicity at Lys(347)
      enhanced molecular interaction of RARalpha with its modulators. This study
      uncovers the first example of lysine trimethylation on a mammalian non-histone
      protein that has an important biological consequence. Our finding also provides
      the evidence for lysine methylation for the family of nuclear receptors for the
      first time.

PMID- 17205980
TI  - Carbonylation of adipose proteins in obesity and insulin resistance:
      identification of adipocyte fatty acid-binding protein as a cellular target of 4
      hydroxynonenal.
AB  - Obesity is a state of mild inflammation correlated with increased oxidative
      stress. In general, pro-oxidative conditions lead to production of reactive
      aldehydes such as trans-4-hydroxy-2-nonenal (4-HNE) and trans-4-oxo-2-nonenal
      implicated in the development of a variety of metabolic diseases. To investigate
      protein modification by 4-HNE as a consequence of obesity and its potential
      relationship to the development of insulin resistance, proteomics technologies
      were utilized to identify aldehyde-modified proteins in adipose tissue. Adipose
      proteins from lean insulin-sensitive and obese insulin-resistant C57Bl/6J mice
      were incubated with biotin hydrazide and detected using horseradish peroxidase
      conjugated streptavidin. High carbohydrate, high fat feeding of mice resulted in
      a approximately 2-3-fold increase in total adipose protein carbonylation.
      Consistent with an increase in oxidative stress in obesity, the abundance of
      glutathione S-transferase A4 (GSTA4), a key enzyme responsible for metabolizing 4
      HNE, was decreased approximately 3-4-fold in adipose tissue of obese mice. To
      identify specific carbonylated proteins, biotin hydrazide-modified adipose
      proteins from obese mice were captured using avidin-Sepharose affinity
      chromatography, proteolytically digested, and subjected to LC-ESI MS/MS.
      Interestingly enzymes involved in cellular stress response, lipotoxicity, and
      insulin signaling such as glutathione S-transferase M1, peroxiredoxin 1,
      glutathione peroxidase 1, eukaryotic elongation factor 1alpha-1 (eEF1alpha1), and
      filamin A were identified. The adipocyte fatty acid-binding protein, a protein
      implicated in the regulation of insulin resistance, was found to be carbonylated
      in vivo with 4-HNE. In vitro modification of adipocyte fatty acid-binding protein
      with 4-HNE was mapped to Cys-117, occurred equivalently using either the R or S
      enantiomer of 4-HNE, and reduced the affinity of the protein for fatty acids
      approximately 10-fold. These results indicate that obesity is accompanied by an
      increase in the carbonylation of a number of adipose-regulatory proteins that may
      serve as a mechanistic link between increased oxidative stress and the
      development of insulin resistance.

PMID- 17205981
TI  - High copper selectively alters lipid metabolism and cell cycle machinery in the
      mouse model of Wilson disease.
AB  - Copper is essential for human physiology, but in excess it causes the severe
      metabolic disorder Wilson disease. Elevated copper is thought to induce
      pathological changes in tissues by stimulating the production of reactive oxygen
      species that damage multiple cell targets. To better understand the molecular
      basis of this disease, we performed genome-wide mRNA profiling as well as protein
      and metabolite analysis for Atp7b-/- mice, an animal model of Wilson disease. We
      found that at the presymptomatic stages of the disease, copper-induced changes
      are inconsistent with widespread radical-mediated damage, which is likely due to
      the sequestration of cytosolic copper by metallothioneins that are markedly up
      regulated in Atp7b-/- livers. Instead, copper selectively up-regulates molecular
      machinery associated with the cell cycle and chromatin structure and down
      regulates lipid metabolism, particularly cholesterol biosynthesis. Specific
      changes in the transcriptome are accompanied by distinct metabolic changes.
      Biochemical and mass spectroscopy measurements revealed a 3.6-fold decrease of
      very low density lipoprotein cholesterol in serum and a 33% decrease of liver
      cholesterol, indicative of a marked decrease in cholesterol biosynthesis.
      Consistent with low cholesterol levels, the amount of activated sterol regulatory
      binding protein 2 (SREBP-2) is increased in Atp7b-/- nuclei. However, the SREBP-2
      target genes are dysregulated suggesting that elevated copper alters SREBP-2
      function rather than its processing or re-localization. Thus, in Atp7b-/- mice
      elevated copper affects specific cellular targets at the transcription and/or
      translation levels and has distinct effects on liver metabolic function, prior to
      appearance of histopathological changes. The identification of the network of
      specific copper-responsive targets facilitates further mechanistic analysis of
      human disorders of copper misbalance.

PMID- 17205982
TI  - Role of trace elements in primary arterial hypertension: is mineral water style
      or prophylaxis?
AB  - A negative relationship between water hardness and cardiovascular mortality rate
      was demonstrated and became a source of interest regarding minerals and trace
      metals in the pathogenesis of atherosclerosis, cardiovascular diseases, and
      arterial hypertension. Higher incidences of sudden death, cerebrovascular
      diseases, arterial hypertension, and coronary heart disease have been reported in
      soft water areas. A major research effort has been devoted to the problem in an
      attempt to find a protective factor in hard water or a detrimental factor or
      element in soft water. The roles of calcium, magnesium, cobalt, lithium,
      vanadium, silicon, manganese, and thallium [corrected] have been considered
      potentially beneficial, whereas those of cadmium, lead, silver, zinc, and
      antimony have been considered potentially harmful. Cobalt and zinc have been
      attributed both roles. In the present article, the role of trace quantities of
      several elements in mineral water in the etiopathogenesis of primary arterial
      hypertension is reviewed.

PMID- 17205983
TI  - Relationship among placental cadmium, lead, zinc, and copper levels in smoking
      pregnant women.
AB  - Previous studies on Cd-exposed pregnant animals have reported a Cd-Zn interaction
      that result in increased placental Cd levels and decreased placental Zn
      transport. In this study, placental Cd, Pb, Cu, and Zn status in pregnant women
      exposed to Cd and Pb through cigarette smoke was investigated. Placental tissues
      obtained from 30 nonsmokers (controls), 70 passive smokers, and 90 smokers were
      analyzed for Cu and Zn levels using an atomic absorption spectrophotometer and
      for Pb and Cd levels using an EG&G PARC Model 303A hanging mercury drop
      electrode. The result showed that whereas the placental Cd and Pb levels in
      smokers were higher that those of nonsmokers, Cu and zinc levels were lower in
      nonsmokers. These results imply that smoking during pregnancy could be harmful
      for both the mother and the fetus.

PMID- 17205984
TI  - Assessment of copper and lipid profile in obese children and adolescents.
AB  - The aim of this study was to assess erythrocyte and plasma copper concentrations
      and correlate them with the lipid profile of overweight and obese children and
      adolescents. The study was performed with 15 overweight and 30 obese children and
      adolescents, and the results were compared to the control group (21), aged 6-16
      yr. Anthropometric assessment was carried out using body mass index (BMI). Total
      cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein
      (HDL) cholesterol, and triglyceride serum levels were investigated. Erythrocyte
      and plasma copper levels were determined by atomic absorption spectrophotometry.
      Greater alterations in the lipid profile were observed in HDL-cholesterol, LDL
      cholesterol, and triglyceride levels, with distinctions according to gender. The
      plasma copper concentrations in the overweight and obese male groups were
      significantly higher than those in the control group (p = 0.0006). Negative
      correlations between plasma copper and total cholesterol (r = -0.54) and LDL
      cholesterol (r = -0.59) were observed in the obese male group. There was no
      statistical difference in copper erythrocyte concentrations. The obesity
      associated to disorders in lipid metabolism predisposes to changes in copper
      plasma concentrations, but there was no alteration in intracellular reserves,
      which suggests an important homeostatic control to compensate for plasma
      oscillations and metabolic alterations of the disease.

PMID- 17205985
TI  - Relationship among TNF-alpha, sICAM-1, and selenium in presurgical patients with
      abdominal aortic aneurysms.
AB  - The purpose of our study was to estimate the utility of tumor necrosis factor
      (TNF), soluble intercellular adhesion molecule-1 (sICAM-1), and selenium (Se)
      measurements as subsidiary parameters for the diagnosis and differentiation of
      large aortic abdominal aneurysms (AAAs). The TNF and sICAM-1 levels in AAAs were
      significantly higher than in the controls. On the contrary, the Se level in AAAs
      was slightly lower; however, the difference was not significant. sICAM-1 did not
      correlate with TNF or Se as well as with any physical parameter. TNF was related
      to body mass index (r = 0.375). A negative correlation was found for Se and the
      aneurysm's diameter (r = -0.382), especially for the height-adjusted diameter (r
      = -0.418). The results of the present study do not allow one to count TNF and
      sICAM-1 as markers of AAA advancement. It was shown for the first time that the
      level of serum Se is low in ruptured aneurysms, but not in the unruptured AAAs.

PMID- 17205986
TI  - Levels of selenium, zinc, copper, and antioxidant enzyme activity in patients
      with leukemia.
AB  - Essential elements, mainly selenium and zinc, were involved in protection against
      oxidative stress in cells. Oxidation could lead to the formation of free radicals
      that have been implicated in the pathogenesis of many diseases, including
      leukemia. Leukemia is a neoplastic disease that is susceptible to antioxidant
      enzyme and essential elements alterations. This study was undertaken to examine
      the levels of essential elements, antioxidant enzymes activities, and their
      relationships with different types of leukemia. Serum selenium, zinc, and copper
      concentrations, red blood cell glutathione peroxidase (GPx) activities, plasma Cu
      Zn superoxide dismutase (Cu-Zn SOD) activities and lipid peroxidation (LPO)
      levels were determined in 49 patients with different types of leukemia before
      initial treatment. Serum selenium and zinc concentrations were lower in leukemia
      patients than those of controls (p<0.01). Serum copper concentration was higher
      in leukemia patients than that of controls (p<0.01). The activities GPx and Cu-Zn
      SOD were significantly increased in leukemia patients, especially with acute
      leukemia (AL), acute lymphoid leukemia (ALL), and acute nonlymphoid leukemia
      (ANLL) (p<0.05), whereas no difference was found between those of chronic
      myelogenous leukemia and the controls. The levels of LPO were normal as controls.
      Serum selenium concentration was not correlated with GPx, and serum levels of
      zinc and copper were not related to Cu-Zn SOD. Serum zinc levels had a negative
      correlation with the absolute peripheral blast cells, whereas serum copper had a
      positive correlation with the absolute peripheral blast cells. Increased GPx and
      Cu-Zn SOD activities and normal levels of LPO, which were a protective responses,
      were an indicator of mild oxidative stress; it might indicate that the essentials
      elements alterations in leukemia patients were mostly dependent on tumor
      activity. Changes of their levels demonstrated that there are low selenium, zinc,
      and high copper status in leukemia patients. The decrease of plasma zinc and
      increase of the Cu/Zn ratio could be the index that showed an unfavorable
      prognosis of acute leukemia.

PMID- 17205987
TI  - Gender differences in selected zinc metabolism parameters in patients with mild
      primary arterial hypertension.
AB  - The relationship between selected zinc (Zn) metabolism parameters, arterial blood
      pressure, age, and renin-angiotensin-aldosterone system in subjects of both sexes
      with mild primary arterial hypertension is presented in this study. The following
      parameters were measured: systolic and diastolic arterial blood pressure, total
      and ouabain-dependent efflux rate constants of Zn from lymphocytes, serum and
      lymphocyte Zn concentrations, serum aldosterone, angiotensin-converting enzyme,
      sodium and potassium concentrations, body mass index, and plasma rennin activity.
      When all subjects are taken into account, no significant age-related differences
      were found for serum Zn. If divided into men and women, negative (r = -0.39) and
      positive (r = 0.34) correlations are observed, respectively. Lymphocyte Zn
      correlated negatively with age in the entire group (r = -0.55) and also for men
      (r = -0.54) and women (r = -0.57). The renin-angiotensin-aldosterone system
      parameters correlated with those of Zn metabolism only for women: plasma rennin
      activity with total Zn efflux from lymphocytes (r = -0.33) and with lymphocyte Zn
      (r = 0.71); the angiotensin-converting enzyme with total Zn efflux from
      lymphocytes (r = -0.35), with the ouabain-dependent Zn efflux from lymphocytes (r
      = -0.33) and with lymphocyte Zn (r = 0.57); serum aldosterone with ouabain
      dependent Zn efflux from lymphocytes (r = -0.44) and with lymphocyte Zn (r =
      0.59). For the men, the only positive correlation was that of serum Zn and
      aldosterone (r = 0.45). In all cases (men and women), there was no negative
      correlation between serum Zn and angiotensin-converting enzyme. In women, the
      diastolic blood pressure correlated negatively with total Zn efflux from
      lymphocytes (r = -0.39), ouabain-dependent Zn efflux from lymphocytes (r = 
      0.49), and serum Zn (r = -0.46); systolic blood pressure correlated negatively
      with lymphocyte zinc (r = -0.38). In men, the systolic blood pressure had a
      negative correlation with lymphocyte zinc (r = -0.32), which was also true for
      the entire group (r = -0.34). These results clearly show gender-related
      differences in Zn metabolism and indicate the need for further research to
      elucidate the possible causes of this phenomenon not only for Zn but for other
      elements as well.

PMID- 17205988
TI  - Selected zinc metabolism parameters in relation to insulin, renin-angiotensin
      aldosterone system, and blood pressure in healthy subjects: gender differences.
AB  - The relationship between the renin-angiotensin-aldosterone system and insulin
      concentration and selected zinc (Zn) metabolism parameters and arterial blood
      pressure in young healthy subjects of both sexes is presented in this study. The
      following parameters were measured: systolic and diastolic arterial blood
      pressure, total and ouabain-dependent efflux rate constants of Zn from
      lymphocytes, serum and lymphocyte Zn concentrations, serum aldosterone,
      angiotensin-converting enzyme, insulin, sodium and potassium concentrations, body
      mass index, and plasma rennin activity. The correlations among these parameters
      show gender-dependent differences, except for a negative correlation between
      serum Zn and ouabain-dependent Zn efflux rate constant and the serum level of
      angiotensin-converting enzyme, and a positive relationship between the total
      efflux rate constant of Zn from lymphocytes and the serum aldosterone levels,
      both of which were gender independent. The results led us to conclude that there
      is a gender-independent functional relation between Zn homeostasis and the renin
      angiotensin-aldosterone system. Insulin does not appear to play a significant
      role in Zn homeostasis.

PMID- 17205989
TI  - Micronutrients and macronutrients and parameters of antioxidative ability in
      saliva of women: inhabitants of Krakow (Poland) in the course of uncomplicated
      singleton pregnancy.
AB  - There were two aims of the present study: (1) to evaluate changes of superoxide
      dismutase (SOD) activity and total antioxidative status measured as the ferric
      reducing ability of plasma (FRAP) concentration in saliva of pregnant women
      during the first, second, and third trimesters of singleton uncomplicated
      pregnancy and (2) to assess possible relations among SOD, FRAP, and intake of
      macronutrients and micronutrients in daily nutritional rations (DNRs) during
      pregnancy. Forty pregnant women aged 27.1+/-5.4 yr (examined group) and 40
      healthy women (the control group) were recruited for this study. The relationship
      between FRAP and SOD in saliva and the intake of macronutrients (proteins,
      carbohydrates, total fat, saturated fatty acid, monounsaturated fatty acids,
      polyunsaturated fatty acids), minerals (Na, K, Ca, P, Mg, Fe, Zn, Cu, Mn), and
      vitamins (A, C, E, B1, B2, B6, PP) in DNR was evaluated by clustering analysis
      with Ward's grouping method. During pregnancy, FRAP and SOD values were lower
      than in the controls, but only for FRAP were the differences statistically
      significant (p < 0.001). For the whole pregnancy period, cluster analysis
      identified two major clusters for which the differentiating variables were SOD
      and retinoids intake, but different patterns for each trimester of pregnancy were
      revealed. The following were concluded: (1) FRAP values were the lowest in the
      second trimester. It suggests that in this trimester of uncomplicated pregnancy,
      women might be not fully adapted to increased demands for antioxidative
      mechanisms. (2) Cluster analysis showed that there were no statistical
      relationships between the intake of micronutrients and macronutrients in DNRs and
      the SOD or FRAP level in the saliva of pregnant women.

PMID- 17205990
TI  - Cerium depresses endocardial endothelial cell-mediated proliferation of cardiac
      fibroblasts.
AB  - Cerium has been implicated in the pathogenesis of cardiac disorders such as acute
      myocardial infarction and endomyocardial fibrosis (EMF). A geochemical hypothesis
      for the causation of EMF linked the cardiac lesions to magnesium deficiency
      consequent to malnutrition and increased cardiac levels of cerium derived from
      monazite soils in the coastal regions of the tropics. We tested the hypothesis
      that the stimulus for fibroblast proliferation and enhanced collagen synthesis in
      EMF is derived from cardiac endothelial cells activated or injured by cerium. We
      explored whether endocardial endothelial cells exposed to cerium secrete factors
      responsible for the increased proliferation and collagen synthesis in cardiac
      fibroblasts. Our results suggest that the growth response of cardiac fibroblasts
      to cerium is not mediated through growth factors secreted by endocardial
      endothelium and that the cardiac lesions in EMF result from direct stimulation of
      subendocardial fibroblasts by cerium.

PMID- 17205991
TI  - Acrodermatitis enteropathica: zinc therapy and possible identification of a
      carrier state through multiple hair zinc analyses over three decades.
AB  - We report on the successful use of repeated hair analyses over three decades to
      monitor zinc and copper status in two siblings with Acrodermatitis enteropathica
      who were treated with oral zinc sulfate beginning in 1975. Furthermore, we report
      for the first time that analysis of zinc in hair over a 30-yr period allows for
      the identification of individuals who might be heterozygous carriers of this
      autosomal recessive disease and who, therefore, would be expected to have hair
      zinc levels intermediate between normal, healthy individuals and those with
      Acrodermatitis enteropathica. Zinc treatment of the two patients with
      Acrodermatitis enteropathica resulted in remission of the signs and symptoms of
      the disease within the first month of therapy. However, any short-term
      interruption (typically, 7-10 d) in oral zinc resulted in an almost immediate
      relapse, with the reappearance of the skin lesions. We also document the inverse
      relationship that exists between zinc and copper through analysis of these metals
      in the scalp hair from the two patients, thus providing a tool for ensuring
      adequate copper intake in patients taking relatively high doses of zinc over a
      long period.

PMID- 17205992
TI  - Changes of heavy metal concentrations in cross-sections of human femur head.
AB  - The concentrations of 12 elements (Ni, Ma, Cr, Cd, Pb, Cu, Fe, Zn, Mg, K, Na, Ca)
      were determined in cross-sections of human femur heads. The highest
      concentrations of these elements was found in the cortical bone, and the lowest
      concentrations occurred in the trabecular bone, with exception of the E cross
      section, in which the lowest values were found in articular cartilage. The
      average concentrations of Na, Ca, K, and Mg were highest in cortical bone and
      lowest in articular cartilage. Pb was found in higher concentrations in articular
      cartilage and lowest in trabecular bone, with exception of cross-sections A and
      E. The Fe contents in the cortical parts were highest in cross-sections A, B, and
      D. Cu was highest in cross-sections B, C, and D of articular cartilage. These
      results show that the contents of the selected metals in the femur head varied
      considerably. As expected, the largest concentrations were found in the outmost
      part of cross-section E and the lowest in its innermost one, possibly related to
      mechanical stress.

PMID- 17205993
TI  - Potential role of serum magnesium measurement as a biomarker of acute falciparum
      malaria infection in adult patients.
AB  - Serum magnesium concentration was measured in 80 adult patients (age range: 18-40
      yr) presenting with acute, uncomplicated falciparum malaria infection and a
      control group of 20 age-matched, healthy individuals. The mean serum magnesium
      concentration in the patients was 1950.0 +/- 10.0 microg/dL. The control serum
      magnesium was 640.0 +/- 40.0 microg/dL. This represents an over threefold
      increase in serum magnesium levels above normal value, p < 0.01. The key
      pathogenic event in acute falciparum malaria infection is the hemolysis of both
      infected and uninfected red blood cells. Therefore, the increased serum magnesium
      concentration might occur because of the hemolysis arising from erythrocytic
      merogony because red blood cells contain high amounts of magnesium. In
      conclusion, the increased serum magnesium has potential application as a
      biomarker of acute falciparum malaria infection in adults.

PMID- 17205994
TI  - Estimation of serum zinc and copper in children with acute diarrhea.
AB  - Diarrhea is, in reality, as much a nutritional disease as one of fluid and
      electrolyte loss. Children who die from diarrhea, despite good management of
      dehydration, are usually malnourished and often severely so. In this study, we
      determined the serum levels of zinc and copper before and after standard oral
      rehydration solution (ORS) therapy in children with acute diarrhea and correlated
      it with diarrheal duration and severity. One hundred ten children suffering from
      acute diarrhea were included. Serum zinc and copper levels of these children were
      estimated at the time of enrollment and after treatment with standard ORS
      therapy. This study shows that children suffering from acute diarrhea show a
      statistically significant decrease of 13.1% and 12.8% in serum zinc and copper
      concentrations, respectively, compared to normal. These levels further decrease
      by 22.6% and 22.4%, respectively, after treatment with standard ORS therapy. Our
      study shows that children with the lower plasma zinc and copper levels suffered
      with more severe and longer duration of diarrhea. Zinc and copper supplementation
      could be added to standard ORS therapy for the reduction in morbidity and
      mortality associated with acute diarrhea in children.

PMID- 17205995
TI  - Urinary zinc excretion is normalized in primary arterial hypertension after
      perindopril treatment.
AB  - Increased or unchanged urinary zinc excretion has been reported in hypertension.
      In the present article, this observation was confirmed in a group of 10 untreated
      hypertensive patients of both sexes that had no diabetes or obesity. The 24-h
      zinc excretion was significantly different between the patients: 7.46+/-3.01
      micromol and healthy controls: 5.19+/-2.19 micromol (p<0.025). After a 1-mo
      treatment with 4 mg perindopril per day, a decrease of urinary zinc was observed
      until it reached levels not significantly different from those of the healthy
      controls (5.98 +/- 2.13 micromol). The decrease was significantly different from
      that of the pretreatment values (p<0.05).

PMID- 17205996
TI  - Differences in selected zinc metabolism parameters in obese and normal-weight
      hypertensive patients following treatment with spironolactone.
AB  - Twenty-three hypertensive outpatients aged 18-53 yr (average: 39.8+/-10.4 yr)
      were classified into two groups according to body mass index (BMI). Six patients
      exceeded the BMI limit, set at 30 kg/m2. All were treated with 100 mg/d
      spironolactone and were subject to before and after measurements of their
      arterial pressure, efflux rate constants of zinc from lymphocytes (total ERCt-Zn
      and ouabain-dependent ERCos-Zn), serum zinc (Zn-s), lymphocyte zinc (Zn-l), serum
      aldosterone (Ald-s), plasma renin activity (PRA), serum sodium (Na-s), and
      potassium (K-s). After 7 d of spironolactone treatment, the ERCt-Zn change in
      normal-weight patients was +0.78+/-0.57, and -0.22+/-0.69 in obese patients. In
      the same manner, the change of ERCos-Zn was +0.59+/-0.94 and -0.025+/-0.32 in
      normal and obese patients, respectively. Serum Zn was increased in normal-weight
      patients but remained unchanged in the obese. The initial lymphocyte zinc values
      were significantly lower in obese patients, but increased up to normal values
      after spironolactone treatment.

PMID- 17205997
TI  - In vitro study of elements in herbal remedies.
AB  - Decreased glucose tolerance is a first sign of diabetes mellitus and therefore
      rigorous control must be taken in carbohydrate and lipid metabolisms. Herbal
      remedies (lyophilized extracts of Myrtilli folium and Phaseoli fructus sine
      seminibus (L1), Myrtilli folium, Phaseoli fructus sine seminibus, and Salviae
      folium (L2) are traditionally used in mid-European folk medicine and in common
      adjuvant therapy for the prevention of complications in type 2 diabetes.
      Significant iron (355.7 +/- 13.8 mg/kg) and zinc (84.73 +/- 1.83 mg/kg)
      concentration was found in L1 and chromium (3.82 +/- 2.71 mg/kg) in L2. Ion
      concentrations in teas made from L1 and L2 are relatively low because the
      quantities of metal ions in teas do not cover the daily need, although the teas
      are good sources for some elements. According to the Recommended Daily
      Allowances, the tea of L1 is a good source for iron and manganese, whereas for
      chromium, the tea of L2 is better. For evaluating the element bioavailability, an
      in vitro dialysis system was applied to determine the element transfer from tea
      of the lyophilized sample to the plasma (buffer pH=7.4). Measurements showed that
      the elements transferred between 6.90% (iron from tea of L2) and 90.05% (chromium
      from tea of L2) through the membrane from teas to the plasma. Metal ions in teas
      of herbal remedies might contribute to the favorable therapeutic effect of
      preventing complications, because they might transfer through the membranes in
      relatively high percentages.

PMID- 17205998
TI  - Trace elements in human tendons and ligaments.
AB  - Tendons and ligaments are key structures in promoting joint movement and
      maintaining joint stability. Although numerous reviews have detailed their
      structure, molecular composition, and biomechanical properties, far less
      attention has been paid to their content of trace elements. Tendons and ligaments
      are generally rich in calcium, sulfur, and phosphorus, although there are
      intriguing differences between one tendon/ligament and another. Furthermore,
      there can be significant regional variations that correlate with the presence or
      absence of fibrocartilage in the "wrap-around" regions of tendons or ligaments,
      where they change direction and press against bone. Here, their sulfate and
      calcium contents are particularly high. This is undoubtedly associated with the
      high levels of proteoglycans that are found in these cartilaginous tissues and
      the occasional presence of sesamoid bones within them.

PMID- 17205999
TI  - Stimulation effect of lithium on the metabolic activity of liver tissue
      mitochondria measured by microcalorimetry.
AB  - The effect of Li(I) on the metabolism of mitochondria isolated from Carassius
      auratus liver tissue was investigated by microcalorimetric method to provide
      evidence for mitochondria hypothesis of bipolar disorder (BPD) and to explore
      therapeutic mechanism of drug for treatment of BPD. Obvious stimulation induced
      by Li(I) on mitochondria metabolism was reflected by power-time (P-t) curves. The
      power-time curves of hepatic mitochondria metabolism without Li(I) could be
      divided into four parts: lag phase, active recovery phase, stationary phase, and
      decline phase. When Li(I) was added, the second heat peak occurred in a
      concentration-dependent sequence. Considering the first heat peak on the P-t
      curves, Li(I) in the range of therapeutic and lower concentration induced slight
      alterations in comparison with the characteristic heat peak observed in the
      control. However, Li(I) above the therapeutic concentration resulted in
      significant changes. Heat output increased with the concentration of Li(I), but
      the rate constant (k2) and the maximum heat power (Pmax2) for the second heat
      peak reached maximum value in the range of therapeutic concentration. Mechanism
      of activation of mitoKatp was suggested and discussed.

PMID- 17206000
TI  - Effects of alpha-tocopherol on serum trace and major elements in rats with
      bleomycin-induced pulmonary fibrosis.
AB  - The study was undertaken to investigate the influence of alpha-tocopherol on
      zinc, copper, iron, calcium, magnesium, and potassium concentrations in serum of
      rats with bleomycin-induced pulmonary fibrosis. Fourteen Wistar albino rats were
      randomly divided into two groups of seven animals each. The first group was
      treated intratracheally with bleomycin hydrochloride (BM group); the second group
      was also instilled with BM but received injections of alpha-tocopherol twice a
      week (BM+E group). The third group was treated in the same manner with saline
      solution only, acting as controls (C). The zinc concentrations of the BM and BM+E
      groups were significantly decreased compared to the controls (p<0.05). The iron
      concentration of the controls was significantly higher than the other two groups.
      The magnesium concentration in the controls and the BM+E group was significantly
      higher than that of the BM group. The serum copper, calcium, and potassium
      concentrations were not found to be statistically different among the three
      groups. Distinct histopathologic changes were found in the BM group compared to
      the untreated rats. Less severe fibrotic lesions were also observed in the BM+E
      group. The results of this study show that lungs of rats treated with bleomycin
      were seriously damaged and that vitamin E seemed to counteract some of the
      damage, as indicated by differences in the serum concentrations of major
      elements.

PMID- 17206001
TI  - Effect of sulfite exposure on zinc, iron, and copper levels in rat liver and
      kidney tissues.
AB  - Sulfite is a potentially toxic molecule that might enter the body via ingestion,
      inhalation, or injection. For cellular detoxification, mammalians rely on sulfite
      oxidase to convert sulfite to sulfate. The purpose of this research was to
      determine the effect of sulfite on zinc, iron, and copper levels in rat liver and
      kidney tissues. Forty normal and sulfite oxidase-deficient male albino rats were
      divided into four groups that included untreated controls (group C), a sulfite
      supplemented group that received 70 mg sodium metabisulfite per kilogram per day
      (group S), a sulfite oxidase-deficient group (group D), and a sulfite oxidase
      deficient group that was also given 70 mg sodium metabisulfite per kilogram per
      day (group DS). The iron and zinc levels in the liver and kidney in groups S and
      DS were not affected by sulfite treatment compared to their respective controls
      (groups C and D). Sulfite exposure led to an increase of kidney copper content in
      the S group when compared to untreated controls. The kidney copper levels were
      significantly increased in the unexposed deficient rats, but it was not different
      than that of the deficient rats that were given oral sulfite treatment. These
      results suggest that kidney copper levels might be affected by exogenous or
      endogenous sulfite.

PMID- 17206002
TI  - Effect of sodium selenite-enriched reperfusion solutions on rat cardiac ischemia
      reperfusion injury.
AB  - Cardiac surgery often generates oxidative stress leading to ischemia reperfusion
      injury (I-R). Antioxidants have been shown to prevent this injury and have been
      added to cardioplegic solutions to assist in recovery. In this study, we tested
      the effectiveness of sodium selenite in protecting against ischemia reperfusion
      injury and investigated the mechanisms behind this protection. Hearts from male
      Wistar rats were subjected to ischemia reperfusion using the Langendorf model.
      Krebs-Henseleit perfusion solutions were supplemented with 0, 0.1, 0.5, 1.0, and
      10 microM sodium selenite. Hearts were perfused for 30 min and then subjected to
      22.5 min of global ischemia followed by 45 min reperfusion. Heart rate, ischemic
      contracture, end diastolic pressure, and developed ventricular pressure were
      monitored. At the completion of the experiment, hearts were homogenized and
      tissue extracts were assayed for glutathione peroxidase (GSH-Px) and thioredoxin
      reductase (Thx-Red) activity. Sodium selenite, at a concentration of 0.5 microM,
      demonstrated a protective effect on the recovery of cardiac function following I
      R, as evidenced by a lower end diastolic pressure and enhanced recovery of rate
      pressure product. There was no beneficial effect observed in hearts perfused with
      0.1 microM sodium selenite-supplemented buffer, whereas poorer functional
      recovery was observed in hearts perfused with 10 microM sodium selenite
      supplemented buffer. The beneficial effect of sodium selenite was not mediated
      through increased activity of GSH-Px or Thx-Red. This study demonstrates that the
      addition of sodium selenite to reperfusion solutions, at an optimal concentration
      of 0.5 microM, assists in cardiac recovery following ischemia reperfusion.

PMID- 17206003
TI  - Effect of iodine supplement on iodine status and 5'-deiodinase activity in the
      brain of neonatal rats with iodine deficiency.
AB  - The weanling Wistar rats of iodine deficiency were divided into three groups for
      supplementation of different levels of iodine (iodine-excessive [IE], iodine
      adequate [IA], and iodine-deficient [ID]), with a control group (C). The iodine
      content in the thyroid was determined by epithermal neutron activation analysis.
      The activities of 5'-deiodinase and 5-deiodinase in the brains were assayed by
      determining the conversion ratios of T4 to T3 and rT3, respectively. The thyroid
      hormones levels in serum were also tested. The results indicated that the ID
      group had a goiter containing a small amount of iodine, but the IE group had a
      slightly swollen thyroid with rich iodine; the concentration of iodine per unit
      mass of thyroid was lower in group IE than in groups IA and C. The highest 5'
      deiodinase and lowest 5-deiodinase activities in group ID and the lowest 5'
      deiodinase activity in group IE were found. The iodine deficiency or excess
      resulted in a compensated hypothyroid state. The results suggest that the iodine
      status and the deiodinases activities would become normal for the rats of iodine
      deficiency if adequate iodine is supplemented soon after birth. Meanwhile, it is
      also critical to avoid excessive intake of iodine to reduce the risk for
      overcorrecting.

PMID- 17206004
TI  - Teniasis: effect on element status of children.
AB  - The aim of this study was to investigate the changes of level of the essential
      elements of copper, magnesium, and zinc status in cases of teniasis in children.
      Copper, magnesium, and zinc levels were measured in 40 children who were positive
      for intestinal parasite of Taenia saginata. Scores were obtained for the
      positives and their 30 age- and sex-matched T. saginata-negative healthy
      children. The mean concentration of copper, magnesium, and zinc in blood showed
      no statistically difference in T. saginata-positive children than in their
      controls both in females (p>0.05) and males (p>0.05). However, a clear
      numerically decrease was observed especially in magnesium and zinc levels
      compared to the controls both in females and males. The average magnesium
      concentration in T. saginata-positive female children and male children were 20+/
      1.9 and 22+/-2.2 mg/L and it was 27+/-2.1 and 27+/-2.3 mg/L in controls,
      respectively. The mean values of the zinc in blood were 0.76+/-0.5 and 0.72+/-0.4
      mg/L in T. saginata-positive female children and male children and 0.85+/-0.3 and
      0.81+/-0.5 mg/L in female and male controls, respectively. No correlation could
      be demonstrated between age and mean values of copper, magnesium, and zinc in T.
      saginata-positive females and males and controls (p>0.05). No significant
      correlation could be found between blood copper, magnesium and zinc levels in T.
      saginata-positive female and male children and controls (p>0.05). Although there
      was no statistical correlation observed in copper, magnesium, and zinc levels
      between patients and controls, there seem to be, especially in magnesium and zinc
      levels, a decrease, whereas no change was seen in the zinc level in children
      infected with T. saginata compared to controls.

PMID- 17206005
TI  - Urinary yttrium excretion and effects of yttrium chloride on renal function in
      rats.
AB  - Evaluation of yttrium exposure in biological samples has not been fully examined.
      To evaluate yttrium nephrotoxicity, yttrium chloride was orally administered to
      male Wistar rats and the urine volume (UV) and N-acetyl-beta-D-glucosaminidase
      (NAG) and creatinine excretion (Crt) were measured in 24-h urine samples. The
      urinary yttrium concentration and excretion rate were determined by inductively
      coupled plasma-argon emission spectrometry (ICP-AES). Large significant decreases
      of UV (>30%) and Crt (>10%) were observed at yttrium doses of 58.3-116.7 mg per
      rat, but no significant NAG changes was observed. This response pattern shows
      that a high yttrium dosage alters glomerular function rather than the proximal
      convoluted tubules. A urinary yttrium excretion rate of 0.216% and good dose
      dependent urinary excretion (r=0.77) were confirmed. These results suggest that
      urinary yttrium is a suitable indicator of occupational and environmental
      exposure to this element, an increasingly important health issue because recent
      technological advances present significant potential risks of exposure to rare
      earth elements. We propose that the ICP-AES analytical method and animal
      experimental model described in this study will be a valuable tool for future
      research on the toxicology of rare earth elements.

PMID- 17206006
TI  - Chromium(III) propionate and dietary fructans supplementation stimulate
      erythrocyte glucose uptake and beta-oxidation in lymphocytes of rats.
AB  - The study describes the effects of 10-wk dietary supplementation with fructans
      (inulin and oligofructose, 5% and 10%, respectively) as well as the biomimetic
      Cr(III) propionate complex (0.5 and 5 mg Cr/kg diet) on blood glucose, insulin,
      glucose transmembrane transport, and beta-oxidation of fatty acids in healthy
      male rats. No significant differences in blood serum glucose concentrations were
      found. Rats fed diets supplemented with the biomimetic complex (5 mg Cr/kg diet)
      had markedly decreased serum insulin level by 15%, whereas the red blood cells
      (RBCs) glucose transmembrane transport and beta-oxidation of fatty acids in white
      blood cells (WBCs) were elevated by 9% and 77%, respectively. These effects were
      accompanied by a slight decrease of the insulin-resistance index. Oligofructose
      and the high-fructan diet (10%) were more effective in increasing the RBCs
      glucose transmembrane transport vs inulin and low-fructan diet (5%). Also, beta
      oxidation of fatty acids in WBCs was increased by 37.5% in groups fed the high
      fructan diet (10%). The results suggest that dietary fructans and the biomimetic
      Cr(III) complex exerted beneficial effects on glucose and lipid metabolism,
      increasing the efficiency of their utilization.

PMID- 17206007
TI  - Metallothionein expression and tissue metal kinetics after partial hepatectomy in
      mice.
AB  - To better elucidate previous results showing that partial hepatectomy noticeably
      changes the tissue content of zinc, calcium, magnesium, and iron(II) ions in
      regenerating the liver, thymus, and spleen, we report on the correlation of these
      metal tissue kinetics in these organs with the expression of metallothionein-I+II
      (MT-I+II) proteins and MT-I mRNA in early postoperative period (1, 2, 6, 12, and
      24 h) after one-third hepatectomy (pHx). The results showed that 2 h after pHx
      the regenerating liver accumulated Zn2+, Ca2+, Mg2+, and Fe2+ ions while
      decreasing the concentration of all these metals in the spleen and of Zn2+ in the
      thymus. On the 24th h, a new high accumulation of Zn2+ and Ca2+ was seen in the
      regenerating liver and of Zn2+, Ca2+, and Fe2+ in the spleen. Simultaneously, MT
      I mRNA increased in the liver and spleen. In hepatocytes and on several spleen
      and thymus mononuclear lymphatic cells, the increased expression of MT proteins
      was found mainly in the cytoplasm and nuclei. The areas expressing MTs in
      regenerating liver inversely correlated with those containing apoptotic cells,
      suggesting that these proteins participate in tissue restoration through
      reduction or increase of metal ions after injury to the liver.

PMID- 17206008
TI  - Zinc supplementation to protein-deficient diet in CO-exposed mice decreased fetal
      mortality and malformation.
AB  - In developing countries, diet during pregnancy is frequently low in both protein
      and zinc contents and exposure to CO is common because of environmental pollution
      and smoking. This study was conducted to evaluate whether zinc supplementation
      ameliorates fetal mortality and malformations in protein-deficient, CO-exposed
      mice. Pregnant mice of the CD-1 strain were maintained on 17% (reference) or 9%
      protein diets mixed with deficient, normal, or supplemental zinc throughout
      gestation. The dams in each dietary group were exposed to air (control) or 500
      ppm CO in air in environmental chambers from gestation days 7-18. As compared to
      the control group (normal protein, normal zinc), the incidence of fetal mortality
      was 66.8% and 57.2% higher, respectively, and malformation incidence was 74.4%
      and 72.4% higher (0 and 500 ppm CO, respectively) in mice fed both deficient
      protein-zinc diets. However, the highest malformation rate was observed in the
      group with normal protein, deficient zinc (96% mortality in both 500 and 0 ppm
      CO, as compared to the reference group, p < 0.0001). The fetal mortality rate was
      -3.5% (0 ppm CO) and 25.4% (500 ppm CO) lower in zinc-supplemented, protein
      deficient groups compared to the control group. There was a significant negative
      association between fetal zinc concentrations and fetal malformations (p < or =
      0.001). The result of this study might be relevant to populations that are
      exposed to CO and or consume marginal zinc and protein diets during gestation.

PMID- 17206010
TI  - Study on the toxic mechanism of La3+ to Escherichia coli.
AB  - The toxic mechanism of La3+ to Escherichia coli is investigated by detecting the
      concentration change of La3+ in E. coli cells growing in La3+-containing medium.
      Stimulatory action and inhibitory effect of La3+ in different concentrations can
      be attributed to the permeability alteration of the cell. Low concentration of
      La3+ increases the nutrition absorbability of the cells from the cultures as a
      result of increased cell permeability, and high concentration of La3+ causes the
      accumulation of La3+ in cells, resulting in the toxic effects on the E. coli
      cells.

PMID- 17206009
TI  - Effect of supplemental magnesium on the kidney levels of cadmium, zinc, and
      copper of mice exposed to toxic levels of cadmium.
AB  - In this report, we present the results of our investigations on the effect of Mg
      pretreatment on Cd and bioelements (Cu and Zn) contents in kidney of mice exposed
      to acute and subacute Cd intoxication. Acute intoxication was performed on male
      Swiss mice given a single oral dose of 20 mg Cd/kg body weight and mice given the
      same dose of Cd but pretreated with 40 mg Mg/kg body weight. For subacute
      intoxication one group of mice was given 10 mg Cd/kg body weight every day, for 2
      wk, and the other one received the same dose of Cd after oral Mg intake of 20
      mg/kg body weight. Cd, Cu, and Zn content was determined in kidney by atomic
      absorption spectrophotometry. In acute Cd intoxication, Mg pretreatment resulted
      in significant decrease of Cd in kidney after 4 and 6 h, compared with animals
      given only Cd. Under the condition of subacute Cd intoxication, Mg
      supplementation reduced Cd kidney content after 2 wk for about 30%, compared with
      animals treated with Cd only. The effect of Mg on Cu and Zn kidney content was
      also beneficial.

PMID- 17206011
TI  - Interaction of an organic selenium compound with human serum albumin: a
      spectroscopic study.
AB  - The interaction between 4,4'-diselenadibenzoic acid and human serum albumin (HSA)
      was investigated by fluorescence and absorption spectroscopy. The quenching
      mechanism of fluorescence of HSA by 4,4'-diselenadibenzoic acid was discussed. It
      is proved that the fluorescence quenching of HSA by 4,4'-diselenadibenzoic acid
      is a result of the formation of the HSA-4,4'-diselenadibenzoic acid complex. The
      binding sites number n, apparent corporation constant K, and corresponding
      thermodynamic parameters, deltaH(theta), deltaG(theta), and deltaS(theta) were
      calculated. Results indicate that the electrostatic interactions forces played
      major role in the reaction.

PMID- 17206012
TI  - Differences in the binding modes of phytochelatin to cadmium(II) and zinc(II)
      ions.
AB  - An 1H NMR (nuclear magnetic resonance) spectroscopic structural analysis of Cd2+
      complexes formed with the pentapeptide phytochelatin, (NH3)+-(gamma-Glu-Cys)2-Gly
      COO- (PC2), at a pH of 7.5 showed that the two thiol groups of the Cys residues
      and either the carbonyl or amide group of the peptide bond between Glu1 and Cys1
      act as possible donor groups in the complexes at Cd2+/PC2 ratios up to 0.4. As
      the ratio increases, the carboxylate group of Glu2 and either the carbonyl or
      amide group of the peptide bond between Cys1 and Glu2 comes to serve as a donor
      group. The manner in which Cd2+ forms complexes with PC2 is distinctly different
      from Zn2+ and might account for the role of phytochelatin in Cd2+ detoxification.
      Electron absorption spectrometry demonstrated that the Cd2+ complexes are
      coordinated in a tetrahedral fashion by four thiol groups and that several sulfur
      atoms might bridge Cd2+ ions, resulting in the formation of polynuclear
      complexes. This contrasts with Zn2+ complex formation, which consists exclusively
      of a 1:1 complex.

PMID- 17206013
TI  - [Screening for lung cancer].

PMID- 17206014
TI  - [Doctors have to do better in the fight against lung cancer].

PMID- 17206015
TI  - [Macular oedema and intravitreal triamcinolone injections].
AB  - PURPOSE: To evaluate the efficacy of intravitreal triamcinolone injections for
      macular oedema in Iceland 2004-2006. METHODS: We reviewed hospital records of 28
      patients who underwent intravitreal injection with triamcinolone acetonide 2004
      2006. Most patients were treated with 8 mg of triamcinolone acetonide. Patients
      were categorized according to the cause of macular oedema (diabetes (n=10),
      phacoemulsification (n=7), branch retinal vein occlusion (BRVO) (n=7) and uveitis
      (n=4)). Best corrected visual acuity was determined before treatment and 1, 3 and
      6 months postoperatively. Intraocular pressure and foveal thickness were measured
      before and after treatment. RESULTS: Visual acuity improved in 4 patients with
      diabetic macular oedema while 5 had unchanged vision. The effect lasted 6 months
      in 8 out of 9 cases. Seven were treated for macular oedema after
      phacoemulsification. Two had improved visual acuity after the injection and 5 had
      unchanged eye sight. The effect lasted for 6 months in every case except for one
      who lost vision. Out of 7 who were treated for macular oedema after BRVO, 3 had
      improved visual acuity and 4 remained unchanged for 6 months. Four patients with
      uveitis got triamcinolone injections and a month after treatment 2 had better
      vision and 2 had unchanged visual acuity. The effect lasted for 6 months in all
      cases but one. In the diabetes and BRVO groups OCT showed a significant reduction
      of foveal thickness. In 4 cases intraocular pressure increased, all of them were
      successfully treated with topical treatment. CONCLUSION: Intravitreal
      triamcinolone improves visual acuity in about 40% of patients with macular
      oedema, about 10% lose vision and about 50% remain unchanged. OCT reveal improved
      anatomic results with significant reduction of foveal thickness and macular
      oedema. No serious complications were noted.

PMID- 17206016
TI  - [Case report: prolonged croup due to herpes simplex infection].
AB  - In recent years only a few cases of croup due to herpes simplex infection among
      healthy children have been reported. This case report concerns a 15 month old,
      healthy boy who was admitted to the Children's Hospital with croup and failed to
      recover within the week. The boy had a positive throat culture for herpes simplex
      type 1 and was diagnosed with croup due to herpes simplex on the basis of
      serology. The boy was treated with corticosteroids; a recognised practice in
      severe cases of croup. The harmful effects of corticosteroids in herpes simplex
      croup, if indeed any, are not known. We surmise that in this case the use of
      corticosteroids was not a decisive factor, but it has been previously noted that
      prolonged corticosteroid treatment can play a role in herpes simplex infection.
      Furthermore it has been debated whether other viral pathogens proceed the
      infection, but in this case serology indicates otherwise.

PMID- 17206017
TI  - [Neonatal life support].
AB  - Although most newborn infants are vigorous at birth, some need to be
      resuscitated. Therefore, at least one person skilled in neonatal resuscitation
      should be present at every delivery and appropriate equipment for resuscitation
      should be available. Most infants who require resuscitation only need respiratory
      support. Chest compressions and administration of medications are infrequently
      needed. This article provides guidelines on neonatal resuscitation, which are
      mainly based on recently published International Liaison Committee on
      Resuscitation (ILCOR) guidelines.

PMID- 17206018
TI  - [The number of psychiatric patients receiving disability compensation is rising.
      Why?].

PMID- 17206019
TI  - [Prevalence of disability in Iceland in December 2005].
AB  - OBJECTIVE: To determine the size and main medical and social characteristics of
      the group of individuals receiving disability benefits in Iceland in December
      2005. MATERIAL AND METHODS: The study includes all those receiving disability
      benefits in Iceland on December 1st 2005 as ascertained by the disability
      register at the State Social Security Institute of Iceland classified by gender,
      age and place of residence. Similar information was obtained on the Icelandic
      population. The prevalence of disability pension was calculated. RESULTS: On
      December 1st 2005 the prevalence of disability pension was 8.6% for females (8.0%
      for the higher and 0.6% for the lower pension level) and 5.5% for males (5.2% for
      the higher and 0.3% for the lower pension level). For females the prevalence of
      disability was lower in the capital region than in other regions, but this was
      not the case for males. The prevalence of disability increased with age. On the
      whole disability was more common among females than males. Mental and behavioural
      disorders and diseases of the musculoskeletal system and connective tissue were
      the most prevalent causes of disability. CONCLUSION: The prevailing trend over
      the last decade of increasing disability in Iceland has continued. Iceland
      appears to lag behind the other Nordic countries in the use of vocational
      rehabilitation and labour marked activation to prevent disability. Ample
      opportunities to slow down this trend are therefore available by greater emphasis
      on such measures.

PMID- 17206020
TI  - [Not all wheezing is asthma. Case report].
AB  - A fifty six year old woman with history of asthma visited a respiratory
      specialist. She had been diagnosed with asthma more than a year previously in a
      primary care clinic. She was treated with inhaled medications without good
      response. A respiratory specialist diagnosed tracheal narrowing secondary to
      thyroid enlargement that was pushing the trachea together. She was cured with a
      thyroid operation. Discussed are differential diagnosis of asthma and causes of
      airway narrowing and the importance of spirometry in diagnosing asthma. KEYWORDS:
      case report, asthma, airway narrowing, spirometry.

PMID- 17206021
TI  - [A new year for The Icelandic Medical Journal].

PMID- 17206023
TI  - Investigation of a tuberculosis cluster at a job centre in Manchester, United
      Kingdom.
AB  - During the summer of 2005, four cases of active tuberculosis from the same
      occupational setting were investigated in Manchester, UK. The index case had been
      diagnosed in December of the previous year. At that stage the closest
      occupational contacts had been screened, all of whom were assessed as being free
      from active disease, and none had met nationally recommended criteria for
      chemoprophylaxis for latent tuberculosis infection (LTBI). In June 2005, two work
      contacts developed progressive primary extrapulmonary (pleural) TB. Following a
      detailed risk assessment, the screening programme was widened to include 137
      staff who worked at the job centre (employment agency) where the first four cases
      had been found. This screening programme was based on tuberculin Mantoux testing,
      CXR and gamma-interferon testing. Of these 137 contacts screened, one additional
      person was found to have active disease and six others were offered
      chemoprophylaxis for LTBI. The isolates from the index case and the first two
      secondary cases were indistinguishable on VNTR-MIRU (variable number tandem
      repeat--mycobacterial interspersed repetitive unit) typing at 15 loci. No samples
      were available for testing from the fourth case of active disease. Management of
      this incident has benefited from the evolving fields of both genotyping and
      diagnostic testing for LTBI. However, further research into the epidemiological
      inferences made through genotyping, as well as the significance of a positive
      gamma-interferon test in assessing the risk of development of active disease, is
      still required.

PMID- 17206025
TI  - Improvement of a national public health surveillance system through use of a
      quality circle.
AB  - Surveillance systems for infectious diseases build the basis for effective public
      health measures in the prevention and control of infectious diseases. Assessing
      and improving the quality of such national surveillance systems is a challenge,
      as many different administrations and professions contribute to a complex system
      in which sensitive information must be exchanged in a reliable and timely
      fashion. We conducted a multidisciplinary quality circle on the national public
      health surveillance system in Germany which included clinicians, laboratory
      physicians, and staff from local and state health departments as well as from the
      Robert Koch-Institut. The recommendations resulting from the quality circle
      included proposals to change the federal law for the control of infectious
      diseases as well as practical activities such as the change of notification forms
      and the mailing of faxed information letters to clinicians. A number of
      recommendations have since been implemented, and some have resulted in measurable
      improvements. This demonstrates that the applied method of quality circle is a
      useful tool to improve the quality of national public health surveillance
      systems.

PMID- 17206024
TI  - Outbreak of Salmonella enterica serotype Manhattan infection associated with meat
      products, France, 2005.
AB  - Between August 2005 and March 2006 in France, 69 cases of Salmonella enterica
      serotype Manhattan (Salmonella Manhattan) were reported, 51 (74%) of them from
      southeastern France. At the time of the alert (November 2005), 13 cases and 33
      controls were interviewed. Cases were more likely than controls to have eaten
      pork sausages (OR=5.9, confidence interval CI [1.3; 26.9]) and beef (OR=9.3, CI
      [1.3; 68.6]). At the same time, 19 strains of Salmonella Manhattan isolated from
      meat products in southeastern France, reported to the French food safety agency
      (Afssa, Agence francaise de securite sanitaire des aliments) in September and
      November 2005, had an indistinguishable PFGE profile to the 7 human isolates of
      Salmonella Manhattan from the outbreak in southeastern France. Trace-back
      investigations revealed that pork samples came from one wholesaler whose pork
      products had tested positive for S. Manhattan during routine food testing in
      August 2005. This wholesaler supplied retail outlets in southeastern France.
      Additionally, a slaughterhouse supplying the wholesaler was inspected and
      widespread contamination with Salmonella spp. and S. Manhattan was found.
      Cooperation between the national agencies in charge of human health (Institut de
      veille sanitaire, InVS) and food safety (Afssa) allowed us to determine the most
      probable source of contamination and to take appropriate control measures.

PMID- 17206026
TI  - A pseudo-outbreak of human A/H5N1 infections in Greece and its public health
      implications.
AB  - The recent wide geographic spread of the highly pathogenic avian influenza A/H5N1
      virus has important public health implications. Several wild migratory birds were
      confirmed to be infected with avian influenza A/H5N1 in Greece in February and
      March 2006. The aim of this paper is to report data from potential H5N1 human
      cases that presented to local hospitals during this period with a respiratory
      infection and expressing concern about exposure to avian influenza. A case
      control investigation was conducted that included case identification with the
      use of a structured definition, review of epidemiological and clinical
      characteristics and molecular testing for avian influenza A/H5N1. The setting was
      the entire country of Greece during February and March 2006. The main outcomes
      were rates of possible cases (meeting both a clinical and an epidemiological
      criterion) and clinical or epidemiological characteristics differentiating them
      from potential cases that met either one of the criteria of a possible case, but
      not both. Twenty six potential patients (81% of whom met a clinical criterion,
      and 39% of whom met an epidemiological criterion) presented and most (85%) were
      admitted in local hospitals during the period of interest. The majority of cases
      (85%) were observed in northern Greece where most of the confirmed A/H5N1 avian
      cases were documented. Five of the 26 evaluated patients met the definition of a
      possible case. These clustered within the early period of confirmed A/H5N1 cases
      in wild migratory birds (P=0.05). Molecular testing was negative for all possible
      cases. Application of a revised case definition constructed according to newer
      European Union guidance resulted in the exclusion of two possible cases. Several
      potential A/H5N1 human cases were recently identified in Greece. Both the timing
      of identification and the geographical location of potential cases suggest an
      increased awareness on the part of the general public, as well as poor
      interpretation of the case definition by the clinicians.

PMID- 17206027
TI  - From evaluation to continuous quality assurance of surveillance systems.

PMID- 17206028
TI  - A/H5N1 in the European Union: current levels of risk to humans, and responding to
      human cases and outbreaks.

PMID- 17206029
TI  - Orientational disorder of [Mg(H2O)6] octahedra in the novel magnesium selenite
      hydrate Mg(SeO3).7.5H2O.
AB  - The crystal structure of magnesium selenite 7.5-hydrate, Mg(SeO3).7.5H2O (space
      group P6(3)/mmc), is characterized by two crystallographically distinct
      [Mg(H2O)6]2+ octahedra, one of which is disordered over two different
      orientations. The selenite groups and water molecules (with partially disordered
      H atoms) bridge the octahedra via hydrogen bonds. All the atoms are located on
      special positions, except for one water molecule.

PMID- 17206030
TI  - Ca1.5 Eu3Sn0.5 O7: a calcium europium tin oxide with a novel structure.
AB  - A new quaternary compound in the Ca-Eu-Sn-O system, namely calcium europium tin
      heptaoxide, Ca1.5 Eu3Sn0.5 O7, was prepared by solid-state reaction at 2073 K.
      All atoms in the structure are on 4i special positions (on mirrors) in space
      group C2/m. Ca/Eu sites are situated within two O octahedra and within two
      sevenfold coordination sites surrounded by O-capped trigonal prisms. A Ca/Eu/Sn
      site is coordinated by five O atoms. The structural formula can be represented as
      (Ca0.28 Eu0.72)(Ca0.16 Eu0.84)(Ca0.46 Eu0.54)(Ca0.28 Eu0.72)(Ca0.32 Eu0.18
      Sn0.50)O7. The crystal structure is a new type and is related to the structure of
      B-form Eu2O3.

PMID- 17206031
TI  - Monoclinic Cu3(SeO3)2Cl2: an oxohalide with an unusual CuO4Cl trigonal
      bipyramidal coordination.
AB  - In single crystals of a new monoclinic (C2/m) form of tricopper(II)
      diselenium(IV) dichloride hexaoxide, Cu3(SeO3)2Cl2, the Se atom is in the 4i
      position, while the two Cu atoms are in 2a and 4i positions. The structure is
      based on layers of CuO4Cl trigonal bipyramids, CuO4 square planes and SeO3E
      tetrahedra. The Cu polyhedra are connected by edge- and corner-sharing to form
      [010] chains and these chains are bridged by the Se atoms to form (001) layers.
      The compound is isostructural with Cu3(TeO3)2Br2.

PMID- 17206032
TI  - Mg2Ru2Cl10O.16H2O.
AB  - Mg2Ru2Cl10O.16H2O {dimagnesium mu-oxo-bis[pentachlororuthenate(IV)]
      hexadecahydrate} crystallizes in the monoclinic system (space group P2(1)/c). The
      structure consists of layers of [Ru2Cl10O]4- anions, [Mg(H2O)6]2+ cations and
      water molecules stacked along the a axis. Only the O atom bonded to Ru occupies
      the 2a site with -1 symmetry. All the other atoms occupy general 4e sites. The
      crystal structure is stabilized by O-H...O and O-H...Cl interactions.

PMID- 17206033
TI  - Bis[bis(methoxycarbimido)amine-kappa2N,N']bis(perchlorato-kappaO)copper(II)
      bis[bis(methoxycarbimido)amine-kappa2N,N']bis(methanol-kappaO)copper(II)
      bis(perchlorate) methanol disolvate.
AB  - The title compound, [Cu(ClO4)2(C4H9N3O2)2][Cu(C4H9N3O2)2(CH4O)2](ClO4)2.2CH3OH,
      comprises two independent Cu(II) species lying on different inversion sites. In
      the Cu complexes, a distorted octahedral geometry arises (from basic square
      planar N4 coordination) from the weak coordination of two perchlorate ions (as Cu
      O) in one species and two methanol molecules in the other (also as Cu-O).
      Interactions between the O atoms of the perchlorate anions or methanol groups and
      the imide or amine NH groups afford an extensive intermolecular hydrogen-bonding
      network.

PMID- 17206034
TI  - Bis(mu-3-nitrobenzene-1,2-dicarboxylato)-kappa8O1,O2:O2,O3;O3,O2:O2,O1
      bis[triaqua(2-carboxy-3-nitrobenzoato-kappa2O,O')lanthanum(III)] dihydrate.
AB  - The title compound, [La2(C8H3NO6)2(C8H4NO6)2(H2O)6].2H2O, consists of dimeric
      units related by an inversion center. The two La(III) atoms are linked by two
      bridging bidentate carboxylate groups and two monodentate carboxylate groups.
      Each La(III) atom is nine-coordinated by six O atoms from five different
      carboxylate groups and three from water molecules. Hydrogen bonds between the
      water molecules and between the solvent water and a carboxylate O atom are
      observed in the structure. In the crystal packing, there are slipped pi-pi
      stacking interactions between the parallel benzene rings. Both hydrogen-bonding
      and pi-pi interactions combine to stabilize the three-dimensional supramolecular
      network.

PMID- 17206035
TI  - Bis(acesulfamato-kappaO4)diaquabis(3-methylpyridine-kappaN)nickel(II).
AB  - In the crystal structure of the title compound [systematic name: diaquabis(6
      methyl-2,2-dioxo-1,2,3-oxathiazin-4-olato-kappaO4)bis(3-methylpyridine
      kappaN)nickel(II)], [Ni(C4H4NO4S)2(C6H7N)2(H2O)2], the Ni(II) centre resides on a
      centre of symmetry and has a distorted octahedral geometry. The basal plane is
      formed by two carbonyl O atoms of two monodentate trans-oriented acesulfamate
      ligands and two trans aqua ligands. The axial positions in the octahedron are
      occupied by two N atoms of two trans pyridine ligands. Molecules are stacked in
      columns running along the a axis. There are pi-pi stacking interactions between
      the molecules in each column, with a distance of 3.623 (2) A between the
      centroids of the pyridine rings. There are also O-H...O interactions between the
      columns.

PMID- 17206036
TI  - An organometallic compound with Z' = 4: {2-[2-(benzylideneamino)phenyl]-1,2
      bis(methoxycarbonyl)ethenyl-kappa2C1,N}iodo(triphenylphosphine
      kappaP)palladium(II).
AB  - The title compound, [Pd(C19H17NO4)I(C18H15P)], crystallizes with four independent
      molecules in the asymmetric unit. The main difference between the molecules is
      the disposition of the PPh3 ligand, for which in each molecule one ring is
      perpendicular to the ligand plane, but may be directed in either direction away
      from the plane; of the four molecules, two represent each possible direction. The
      independent molecules are arranged to form a chain parallel to [101] with an
      approximate translation of (a+c)/4 between successive molecules, excluding the
      PPh3 rings. This leads to a systematic weakness of the reflections with h + l not
      equal 4n.

PMID- 17206037
TI  - A novel mixed-valence copper complex, poly[[mu2-4,4'-bipyridine-mu3-pyridine
      2,4,6-tricarboxylato-dicopper(I,II)] monohydrate].
AB  - In the title novel mixed-valence copper complex, {[Cu2(C8H2NO6)(C10H8N2)].H2O}n,
      the Cu(I) and Cu(II) ions are linked by 4,4'-bipyridine (bpy) and pyridine-2,4,6
      tricarboxylate (ptc) ligands into corrugated layers, which are assembled via
      interlayer C-H...O hydrogen bonds to give a three-dimensional supramolecular
      architecture.

PMID- 17206038
TI  - catena-Poly[[bis(mu2-4-methylbenzoato-kappa2O:O')disilver(I)(Ag-Ag)]-mu2-di-2
      pyridylamine-kappa2N2:N2'] and catena-poly[[(di-2-pyridylamine-kappaN2)(mu2-4
      nitrobenzoato-kappa2O:O')disilver(I)(Ag-Ag)]-mu3-4-nitrobenzoato-kappa3O:O':O'].
AB  - Both title compounds are polynuclear polymeric complexes with binuclear units. In
      the former compound, [Ag2(C8H7O2)2(C10H9N3)]n, the two Ag(I) atoms display
      distorted square-planar coordinations. This compound contains a twofold axis and
      a crystallographic inversion centre, and di-2-pyridylamine (DPA) ligands
      crosslink adjacent binuclear units to form infinite polymeric chains. Crystal
      packing is stabilized by van der Waals interactions and partial pi-pi stacking
      interactions between the chains. The latter compound, [Ag2(C7H4NO4)2(C10H9N3)]n,
      contains crystallographic inversion centres and the two Ag(I) atoms exhibit two
      types of distorted square-pyramidal coordination. Ag-Ag argentophilic
      interactions and Ag-O crosslinking between adjacent binuclear units contribute to
      form infinite polymeric chains. Weak pi-pi stacking interactions are observed in
      the polymer chain. Crystal packing is stabilized by C-H...O hydrogen bonds and by
      weak pi-pi stacking interactions.

PMID- 17206039
TI  - 1,4,8,11-Tetraazacyclotetradecane antimony(III) sulfide.
AB  - Poly[1,4,8,11-tetraazacyclotetradecane(2+) [hepta-mu-sulfido
      trisulfidohexaantimony(III)]], {(C10H26N4)[Sb6S10]}n, consists of novel [Sb6S10]2
      layers containing Sb2S2, Sb4S4 and Sb7S7 hetero-rings, which are separated by
      macrocyclic amine molecules. The macrocyclic amine molecules are disordered over
      two crystallographically distinct positions and are diprotonated in order to
      balance the charge of the anionic layers.

PMID- 17206040
TI  - A new trinuclear cobalt(II) complex: decaaqua-1kappa3O,2kappa4O,3kappa3O
      bis(benzene-1,3,5-tricarboxylato)-1kappaO,3kappaO-di-mu-4,4'-bipyridine
      1:2kappa2N:N';2:3kappa2N:N'-di-4,4'-bipyridine-1kappaN,3kappaN-tricobalt(II) 4,4'
      bipyridine solvate octahydrate.
AB  - The principal building units in the title compound,
      [Co3(C9H3O6)2(C10H8N2)4(H2O)10].C10H8N2.8H2O, are the linear centrosymmetric
      tricobalt(II) complex molecules resulting from two square-pyramidal
      [Co(btc)(bpy)(H2O)3]- entities (bpy is 4,4'-bipyridine and btc is the benzene
      1,3,5-tricarboxylate trianion) bridged by one trans-[Co(bpy)2(H2O)4]2+ unit. The
      trinuclear complex molecules are assembled into infinite chains through
      intermolecular O-H...N hydrogen bonds and pi-pi stacking interactions between
      adjacent monodentate bpy ligands. The chains and uncoordinated bpy molecules are
      further assembled into two-dimensional open layers, which are stacked in a
      staggered manner to give a three-dimensional supramolecular architecture with the
      solvent water molecules in the cavities.

PMID- 17206041
TI  - Poly[diaqua(mu-4,4'-bipyridine)tetrakis(mu
      ferrocenecarboxylato)bis(ferrocenecarboxylato)trimanganese(II)].
AB  - The title compound, [Mn3Fe6(C5H5)6(C6H4O2)6(C10H8N2)(H2O)2]n, consists of two
      crystallographically unique Mn(II) centers. One is situated on an inversion
      center and is octahedrally coordinated by two N atoms from two bridging 4,4'
      bipyridine (4,4'-bipy) ligands and four O atoms, two from different bridging
      ferrocenecarboxylate (mu2-FcCOO-; Fc is ferrocene) units and two from aqua
      ligands. The two halves of each 4,4'-bipy ligand are related by a center of
      symmetry. The second Mn(II) center is in a strongly distorted tetragonal
      pyramidal geometry, coordinated by five O atoms, three from three mu2-FcCOO-
      units and two from a fourth, chelating, eta2-FcCOO- unit. The FcCOO- units
      function as bridging ligands to adjacent Mn(II) centers, leading to the formation
      of linear ...Mn1Mn2Mn2Mn1... chains. Adjacent chains are further bridged by 4,4'
      bipy ligands, resulting in a two-dimensional layered polymer.

PMID- 17206042
TI  - Two square-planar palladium(II) complexes with P,O-bidentate hybrid ligands.
AB  - In the two square-planar palladium(II) complexes
      chloro[(diphenylphosphinoamino)diphenylphosphine oxide]methylpalladium(II)
      dimethyl sulfoxide solvate, [Pd(CH3)Cl(C24H21NOP2)].C2H6OS, (I), and chloro{[2
      (diphenylphosphino)phenyl]diethoxymethane}methylpalladium(II),
      [Pd(CH3)Cl(C23H25O2P)], (II), a trans disposition of the diphenylphosphino and
      chloro groups is observed. The Pd atom in both complexes displays a distorted
      square-planar configuration formed by the four unique donor atoms (P, Cl, C and
      O). In compound (I), the five-membered Pd-P-N-P-O metallacycle is best described
      as having an envelope conformation, whereas in (II) the six-membered Pd-P-C-C-C-O
      metallacycle adopts a skewed boat conformation. Furthermore, within the P-N-P-O
      backbone in (I), the P-N distances are consistent with single-bond character
      [1.659 (3) and 1.692 (3) A], whilst the P=O bond shows appreciable double-bond
      character [1.509 (2) A].

PMID- 17206043
TI  - Bis(tert-butylsulfonyl)ethyne and 1-tert-butylsulfinyl-2-tert
      butylsulfonylethyne.
AB  - The title compounds are electron-poor ethynes. The structure determination of
      bis(tert-butylsulfonyl)ethyne, C10H18O4S2, (I), is the first of a bis-sulfonyl
      substituted ethyne. The molecule is situated on a crystallographic inversion
      centre. The S-Csp bond [1.737 (2) A] is the longest of this type reported to
      date. 1-tert-Butylsulfinyl-2-tert-butylsulfonylethyne, C10H18O3S2, (II), which is
      basically the same as (I) minus one O atom, crystallizes isomorphous with (I).
      This results in a nearly equal distribution of the three O atoms over the four
      possible positions.

PMID- 17206044
TI  - Conformation and structure of bis(glycyl-L-aspartic acid) oxalate 0.4-hydrate.
AB  - The title bis(glycyl-L-aspartic acid) oxalate complex {systematic name: bis[2-(2
      ammonioacetamido)butanedioic acid] oxalate 0.4-hydrate}, 2C6H11N2O5+.C2O4(2
      ).4H2O, crystallizes in a triclinic space group with the planar peptide unit in a
      trans conformation. The asymmetric unit consists of two glycyl-L-aspartic acid
      molecules with positively charged amino groups and neutral carboxyl groups, and
      an oxalate dianion. The twist around the C-Calpha bond indicates that both the
      peptide molecules adopt extended conformations, while the twist around the N
      Calpha bond shows that one has a folded and the other a semi-extended state. The
      present complex can be described as an inclusion compound with the dipeptide
      molecule as the host and the oxalate anion as the guest. The usual head-to-tail
      sequence of aggregation is not observed in this complex, as is also the case with
      the glycyl-L-aspartic acid dihydrate molecule. The study of aggregation and
      interaction patterns in binary systems is the first step towards understanding
      more complex phenomena. This further leads to results that are of general
      interest in bimolecular aggregation.

PMID- 17206045
TI  - o-Chloro- and o-bromobenzonitrile: pseudosymmetry and pseudo-isostructural
      packing.
AB  - The structures of o-chlorobenzonitrile, C7H4ClN, (I), and o-bromobenzonitrile,
      C7H4BrN, (II), have similar packing arrangements, even though Z' = 4 in (I) and
      Z' = 1 in (II). Both structures involve X...N interactions, as well as weak C
      H...X and C-H...N hydrogen bonds. The four crystallographically independent
      molecules in (I) are related by pseudosymmetry.

PMID- 17206046
TI  - Hydrogen bonding in two solid phases of phenazine-chloranilic acid (1/1)
      determined at 170 and 93 K.
AB  - The crystal structures in two solid phases, i.e. phase II stable between 146 and
      253 K and phase IV below 136 K, of the title compound [phenazine-chloranilic acid
      (1/1), C12H8N2.C6H2Cl2O4, in phase II, and phenazinium hydrogen chloranilate,
      C12H9N2+.C6HCl2O4-, in phase IV], have been determined. Both phases crystallize
      in P2(1), and each structure was refined as an inversion twin. In phase II, the
      phenazine and chloranilic acid molecules are arranged alternately through two
      kinds of O-H...N hydrogen bonds. In phase IV, salt formation occurs by donation
      of one H atom from the chloranilic acid molecule to the phenazine molecule; the
      resulting monocation and monoanion are linked by N-H...O and O-H...N hydrogen
      bonds.

PMID- 17206047
TI  - Three substituted 4-pyrazolylbenzoates: hydrogen-bonded supramolecular structures
      in one, two and three dimensions.
AB  - The molecules of ethyl 4-(5-amino-3-methyl-1H-pyrazol-1-yl)benzoate, C13H15N3O2,
      are linked by two independent N-H...O hydrogen bonds into a chain of edge-fused
      and alternating R(4)2(8) and R(2)2(20) rings. A combination of N-H...N and N
      H...O hydrogen bonds links the molecules of methyl 4-(5-amino-3-tert-butyl-1H
      pyrazol-1-yl)benzoate, C15H19N3O2, into sheets of alternating R(2)2(20) and
      R(6)6(32) rings. In 4-(5-amino-3-methyl-1H-pyrazol-1-yl)benzoic acid monohydrate,
      C11H11N3O2.H2O, the molecular components are linked into a three-dimensional
      framework structure by a combination of five independent hydrogen bonds, two of O
      H...N type and one each of O-H...O, N-H...O and N-H...N types.

PMID- 17206048
TI  - 7-Amino-2-tert-butyl-5-methylpyrazolo[1,5-a]pyrimidine: a three-dimensional
      framework structure built from two N-H...N hydrogen bonds.
AB  - The bond distances in the title compound, C11H16N4, provide evidence for
      peripheral delocalization of pi electrons. The molecules are linked by two
      independent N-H...N hydrogen bonds into a three-dimensional framework structure.

PMID- 17206049
TI  - Hydrogen-bonded chains in 3-tert-butyl-5-[(4-methoxybenzyl)amino]-1-phenyl-1H
      pyrazole and tetramolecular hydrogen-bonded aggregates in 5-[(benzotriazol-1
      ylmethyl)(4-methoxybenzyl)amino]-3-tert-butyl-1-phenyl-1H-pyrazole.
AB  - The molecules of 3-tert-butyl-5-[(4-methoxybenzyl)amino]-1-phenyl-1H-pyrazole,
      C21H25N3O, are linked into simple C9 chains by a single C-H...N hydrogen bond. 5
      [(Benzotriazol-1-ylmethyl)(4-methoxybenzyl)amino]-3-tert-butyl-1-phenyl-1H
      pyrazole, C28H30N6O, crystallizes with Z' = 2 in the space group P2(1)/c. The
      molecules are weakly linked into centrosymmetric tetramolecular aggregates by a
      combination of C-H...N and C-H...O hydrogen bonds.

PMID- 17206050
TI  - Three ethyl 5-amino-1-aryl-1H-imidazole-4-carboxylates: hydrogen-bonded
      supramolecular structures in one, two and three dimensions.
AB  - The molecules of ethyl 5-amino-1-(4-cyanophenyl)-1H-imidazole-4-carboxylate,
      C13H12N4O2, are linked into a chain of alternating R(2)2(10) and R(4)4(34) rings
      by a combination of N-H...N and C-H...N hydrogen bonds. In ethyl 5-amino-1-(4
      chlorophenyl)-1H-imidazole-4-carboxylate, C12H12ClN3O2, where the ethyl group is
      disordered over two sets of sites, a combination of N-H...O, N-H...N, C-H...N and
      C-H...pi(arene) hydrogen bonds links the molecules into complex sheets. Two
      intermolecular hydrogen bonds, one each of N-H...N and C-H...O types, link the
      molecules of ethyl 5-amino-1-(2,6-difluorophenyl)-1H-imidazole-4-carboxylate,
      C12H11F2N3O2, into a continuous three-dimensional framework structure.

PMID- 17206051
TI  - Hydrogen-bonded chains of rings in methyl 4-[(5-methyl-1H-pyrazol-3-yl)amino]-3
      nitrobenzoate and hydrogen-bonded sheets in methyl 1-(5-methyl-1H-pyrazol-3-yl)
      1H-benzimidazole-5-carboxylate.
AB  - Molecules of methyl 4-[(5-methyl-1H-pyrazol-3-yl)amino]-3-nitrobenzoate,
      C12H12N4O4, (I), exhibit a polarized (charge-separated) structure in the
      nitroaniline portion. The molecules are linked into chains of edge-fused
      R(2)2(16) and R(2)2(22) rings by a combination of N-H...O(carbonyl) and C
      H...O(nitro) hydrogen bonds. Methyl 1-(5-methyl-1H-pyrazol-3-yl)-1H-benzimidazole
      5-carboxylate, C13H12N4O2, (II), which is readily formed from (I) by reduction
      followed by ring formation, crystallizes with Z' = 2 in the space group P-1. Each
      of the two independent molecular types is linked into sheets of R(4)4(28) rings
      by a combination of N-H...N and C-H...O(carbonyl) hydrogen bonds.

PMID- 17206052
TI  - A new pseudopolymorph of hexakis(4-cyanophenyl)benzene.
AB  - The title compound (systematic name: benzene-4,4',4'',4''',4'''',4'''''
      hexaylhexabenzonitrile dichloromethane disolvate), C48H24N6.2CH2Cl2, crystallizes
      as an inclusion compound during the slow diffusion of methanol into a solution of
      hexakis(4-cyanophenyl)benzene in CH2Cl2. The hexakis(4-cyanophenyl)benzene
      molecule lies on an axis of twofold rotation in the space group Pbcn. Weak C
      H...N interactions between hexakis(4-cyanophenyl)benzene molecules define an open
      network with space for including guests. The resulting structure is a new
      pseudopolymorph of hexakis(4-cyanophenyl)benzene. The eight known
      pseudopolymorphs have few shared architectural features, in part because none of
      the intermolecular interactions that are present plays a dominant role or forces
      neighboring molecules to assume particular relative orientations.

PMID- 17206053
TI  - 3-Nitrobenzaldehyde isonicotinoylhydrazone monohydrate redetermined at 120 K:
      sheets built from O-H...O, O-H...N, N-H...O and C-H...O hydrogen bonds.
AB  - In the title compound, C13H10N4O3.H2O, the molecular components are linked into
      complex sheets by a combination of four types of hydrogen bonds.

PMID- 17206054
TI  - Cyclic trihydroxamic acid derivatives.
AB  - In the crystal structures of two cyclic trihydroxamic acid derivatives containing
      the same substructure unit, viz. 1,3,5-trihydroxy-1,3,5-triazinane-2,4,6-trione
      dihydrate, C3H3N3O6.2H2O, (I), and 1,3,5-benzyloxy-1,3,5-triazinane-2,4,6-trione,
      C24H21N3O6, (II), there is no significant difference in the geometric parameters.
      In (I), there are 11 hydrogen bonds of the O-H...O type interconnecting the
      molecules in a three-dimensional network, while in (II) there are only two weak C
      H...O hydrogen bonds. The results of IR spectroscopic analysis are in good
      agreement with the crystallographic study.

PMID- 17206055
TI  - Diisopropylammonium 2-[(2,4-dinitrophenyl)sulfanylaminocarbonyl]benzoate.
AB  - The structure of title compound, C6H16N+.C14H8N3O7S-, comprises discrete ions
      which are interconnected by N-H...O- and N-H+...O- hydrogen bonds, leading to a
      neutral one-dimensional network along [100]. These hydrogen bonds appear to
      complement the Coulombic interaction and help to stabilize the structure further.

PMID- 17206056
TI  - Hydrogen bonding and pi-pi stacking in 6-hydroxybiochanin A monohydrate.
AB  - In the lattice of the title compound (systematic name: 5,6,7-trihydroxy-4'
      methoxyisoflavone monohydrate), C16H12O6.H2O, the isoflavone molecules are linked
      into chains through R(4)3(17) motifs composed via O-H...O and C-H...O hydrogen
      bonds. Centrosymmetric R(4)2(14) motifs assemble the chains into sheets. Hydrogen
      bonding and aromatic pi-pi stacking interactions lead to the formation of a three
      dimensional network structure.

PMID- 17206057
TI  - 2'-Deoxy-5-propynylcytidine: a nucleoside forming two solid-state conformations.
AB  - The title compound, 4-amino-1-(2-deoxy-beta-D-erythropentofuranosyl)-5-(prop-1
      ynyl)pyrimidin-2(1H)-one, C12H15N3O4, shows two conformations in the crystalline
      state which differ mainly in the glycosylic bond torsion angle and the sugar
      pucker. Both molecules exhibit an anti glycosylic bond conformation, with torsion
      angles chi = -135.0 (2) and -156.4 (2) degrees for molecules 1 and 2,
      respectively. The sugar moieties show a twisted C2'-endo sugar pucker (S-type),
      with P = 173.3 and 192.5 degrees for molecules 1 and 2, respectively. The crystal
      structure is characterized by a three-dimensional network that is stabilized by
      several intermolecular hydrogen bonds between the two conformers.

PMID- 17206058
TI  - Pearls on a string: a Z' = 7 structure for glycyl-L-valine.
AB  - The title peptide, C7H14N2O3, crystallizes with seven independent molecules in
      the asymmetric unit. All have essentially the same overall conformation, but some
      flexibility is exhibited by the glycine residue. It appears that the high Z'
      value, observed only three times before for an organic compound, permits
      formation of shorter hydrogen bonds in one of the two head-to-tail chains
      involving the N-terminal amino groups and the C-terminal carboxylate groups than
      found in a hypothetical model structure of glycyl-L-valine with Z' = 1, and that
      it furthermore alleviates strain associated with an eclipsed orientation of the
      amino group.

PMID- 17206059
TI  - Hydrogen phosphate and dihydrogen phosphate salts of 4-aminoazobenzene.
AB  - 4-Amino-trans-azobenzene {or 4-[(E)-phenyldiazenyl]aniline} can form isomeric
      salts depending on the site of protonation. Both orange bis{4-[(E)
      phenyldiazenyl]anilinium} hydrogen phosphate, 2C12H12N3+.HPO4(2-), and purple 4
      [(E)-phenyldiazenyl]anilinium dihydrogen phosphate phosphoric acid solvate,
      C12H12N3+.H2PO4-.H3PO4, (II), have layered structures formed through O-H...O and
      N-H...O hydrogen bonds. Additionally, azobenzene fragments in (I) are assembled
      through C-H...pi interactions and in (II) through pi-pi interactions. Arguments
      for the colour difference are tentatively proposed.

PMID- 17206060
TI  - Cyano-stabilized triphenylphosphonium ylids.
AB  - Crystalline cyano-stabilized triphenylphosphonium ylids with keto or ester groups
      give rise to an extended electronic delocalization. In methyl 2-cyano-2
      (trimethylphosphonio)ethenoate, Ph3P=C(CN)CO2CH3 or C22H18NO2P, (I), and 1-cyano
      1-(trimethylphosphonio)prop-1-en-2-olate, Ph3P=C(CN)CO-CH3 or C22H18NOP, (II),
      the carbonyl groups are oriented toward the cationoid P atom. Bond lengths and
      angles, torsion angles and P...O contact distances are consistent with a dominant
      coplanar conformation where the molecular structures are the result of a balance
      between intra- and intermolecular interactions. The main interactions presented
      by cyano-ester (I) and cyano-keto (II) are intramolecular interactions between
      the carbonyl O and the P atoms. In addition, both compounds show other less
      important intramolecular interactions between the carbonyl O and phenyl H atoms,
      which could contribute to form a preferred conformation in the crystal structure.

PMID- 17206061
TI  - 2,3-Dimethoxybenzaldehyde isonicotinoylhydrazone chloroform monosolvate, and the
      mono- and dihydrates of 3,4,5-trimethoxybenzaldehyde isonicotinoylhydrazone:
      hydrogen-bonded supramolecular structures in one, two and three dimensions.
AB  - In 2,3-dimethoxybenzaldehyde isonicotinoylhydrazone chloroform monosolvate,
      C15H15N3O3.CHCl3, the hydrazone molecules are linked by a combination of N-H...N
      and C-H...N hydrogen bonds into chains from which the chloroform molecules are
      pendent. 3,4,5-Trimethoxybenzaldehyde isonicotinoylhydrazone forms two
      stoichiometric hydrates. In the monohydrate, C16H17N3O4.H2O, the components are
      linked into sheets by a combination of O-H...O, O-H...N and N-H...N hydrogen
      bonds, and in the dihydrate, C16H17N3O4.2H2O, a combination of O-H...O, O-H...N
      and N-H...O hydrogen bonds links the components into a three-dimensional
      framework structure.

PMID- 17206062
TI  - The concomitant crystallization of two polymorphs of 1-deoxy-alpha-D-tagatose.
AB  - The crystalline form of 1-deoxy-D-tagatose, C6H12O5, is shown to be 1-deoxy-alpha
      D-tagatopyranose; the absolute configuration is determined by use of D-lyxono-1,4
      lactone as the starting material. The title compound crystallized as concomitant
      polymorphs from a mixture of ethyl actate and methanol. Although the melting
      points of the materials differ by 7 K, the molecular conformations are almost
      identical and, in both polymorphs, each molecule is subject to four O-H...O
      hydrogen bonds.

PMID- 17206063
TI  - Secondary interactions in two related terphenyl derivatives: 2',5'-dimethyl-p
      terphenyl and 2',5'-bis(bromomethyl)-p-terphenyl.
AB  - In 2',5'-dimethyl-p-terphenyl, C20H18, which displays pseudosymmetry (the true
      space group is Pna2(1), but less satisfactory refinement can also be achieved in
      Pbcn), the molecules are linked into chains by two short C-H...pi interactions to
      the centroid of the central ring. In 2',5'-bis(bromomethyl)-p-terphenyl,
      C20H16Br2, the polar CH2Br groups cause molecules to aggregate via C-H...Br and
      Br...Br interactions, forming a layer structure, in which the phenyl rings
      project outwards from the central, more polar, region.

PMID- 17206065
TI  - The crystal structure of tRNA.

PMID- 17206064
TI  - Early days of tRNA research: discovery, function, purification and sequence
      analysis.

PMID- 17206066
TI  - The genetic code - thawing the 'frozen accident'.

PMID- 17206067
TI  - The discovery of modified nucleosides from the early days to the present: a
      personal perspective.

PMID- 17206068
TI  - The early history of tRNA recognition by aminoacyl-tRNA synthetases.

PMID- 17206069
TI  - Chemistry of aminoacylation and peptide bond formation on the 3'terminus of tRNA.

PMID- 17206070
TI  - A revolution in liver ultrasound.
AB  - Liver ultrasound has been revolutionized by the development of microbubble
      contrast agents and multipulse software designed to detect their nonlinear
      resonances. The ability to visualize all parts of the liver's vasculature,
      including the sinusoids, at high spatial and temporal resolution gives unique
      insights into the haemodynamics of focal liver lesions. It has enabled ultrasound
      to detect and, as described by Celli N, et al.Eur J Gastroenterol Hepatol 2007; 3
      14, to characterize such lesions with an accuracy comparable to multidetector
      computed tomography with consequent improvements in patient handling.

PMID- 17206071
TI  - Characterization of liver lesions by real-time contrast-enhanced ultrasonography.
AB  - OBJECTIVE: The aim of this study was to identify the most common patterns of
      various common liver lesions at real-time contrast-enhanced ultrasonography with
      second-generation contrast agents and their role in the differentiation of
      malignant from benign lesions. PATIENTS AND METHODS: The enhancement pattern in
      the arterial phase and its modifications in subsequent portal and sinusoidal
      phases were separately evaluated in (i) 171 liver lesions detected at
      conventional ultrasonography in 125 noncirrhotic patients (87 metastases, six
      cholangiocellular carcinoma, 38 focal nodular hyperplasia, 30 hemangiomas, seven
      focal fatty sparing/changes, two hepatocellular adenomas and one hepatocellular
      carcinoma) and (ii) 75 lesions detected in 67 cirrhotic patients (66
      hepatocellular carcinoma and nine dysplastic nodules). The final diagnosis was
      made by contrast-enhanced helical computed tomography and/or magnetic resonance
      imaging or by ultrasonography-guided biopsy when the diagnosis was equivocal at
      conventional imaging techniques (45 lesions). RESULTS: In noncirrhotic patients,
      the hypoechoic pattern in portal and sinusoidal phase (rapid washout) or the
      markedly hypoechoic or anechoic pattern in sinusoidal phase (marked late washout)
      showed a sensitivity, specificity and accuracy of 96.8, 100 and 98.2% for the
      diagnosis of malignancy. In cirrhotic patients, early arterial enhancement showed
      a sensitivity of 93.9% for the diagnosis of malignancy, with a specificity as low
      as 55.5% given the presence of arterial enhancement in 5/9 nodules resulted
      dysplastic at histological analysis. CONCLUSION: Real-time contrast-enhanced
      ultrasonography provides sensitive and specific criteria for the differential
      diagnosis between benign and malignant liver lesions, and in most cases it may
      replace more expensive and invasive imaging techniques.

PMID- 17206072
TI  - Antibiotic therapy: a major cause of drug-induced jaundice in southwest England.
AB  - OBJECTIVE: To determine the incidence and causes of drug-induced jaundice in a
      rural community. METHODS: A retrospective analysis of 800 patients presenting to
      a single-centre jaundice referral system serving a community of 400 000 over a
      period of 66 months (1998-2004). Standard criteria for drug-induced liver injury
      were applied to patients with a putative diagnosis of drug-induced jaundice. The
      incidence rates per prescription of drug-induced jaundice caused by co-amoxiclav
      and flucloxacillin were derived from local and national annual prescription
      rates. RESULTS: The incidence of drug-induced jaundice was 1.27 (confidence
      limits 0.85-1.8) per 100 000 per annum in a total of 28 patients (17 men, mean
      age 69 years). Antibiotics were the commonest cause of jaundice (n=21). Of these,
      co-amoxiclav (n=9) and flucloxacillin (n=7) caused the majority with an incidence
      rate per 100 000 prescriptions of 9.91 (4.6-18.0) and 3.60 (1.5-7.2),
      respectively. Co-amoxiclav-induced jaundice was observed more commonly in elderly
      males (age 65 years, M : F 7 : 2). In those patients with flucloxacillin or co
      amoxiclav-induced jaundice, bilirubin ranged from 54 to 599 mumol/l (267 mumol/l)
      with a resolution of jaundice between 30 and 90 days. Counselling with regard to
      potential drug-induced liver injury and reporting of the adverse reaction had
      been performed in 1/28 patients. CONCLUSIONS: 8.1% patients with no biliary
      obstruction and jaundice had a drug-induced and predominantly antibiotic-related
      aetiology particularly affecting an elderly population. We recommend that all
      patients receiving co-amoxiclav and flucloxacillin should be counselled before
      the therapy regarding the potential risk of jaundice and that an alternative
      antibiotic to co-amoxiclav is used if possible in men over the age of 60 years.

PMID- 17206073
TI  - Prognostic value of immunohistochemistry in gastric neuroendocrine (carcinoid)
      tumors.
AB  - Three subtypes of enterochromaffin-like cell tumors (carcinoids) have been
      described: type I, associated with chronic atrophic gastritis; type II, multiple
      endocrine neoplasia 1 and Zollinger-Ellison syndrome; and type III, sporadic
      tumors. OBJECTIVES: (i) To investigate the immunoexpression of Ki-67, p53 and Bcl
      2 proteins in enterochromaffin-like cell (carcinoid) tumors and (ii) to evaluate
      the prognostic value of these markers. METHODS: Fifty-four samples from 21
      patients with gastric carcinoid tumors were sectioned and immunostained using
      avidin-biotin peroxidase method. RESULTS: The mean age was 62.2+/-11.4 years (36
      83 years-old) and 13 (61.9%) were women. Type I lesions were detected in 61.9%
      and type III in 38.1%. Tumors were single in 10 (47.6%) and were multiple and/or
      multicentric in 11 (52.4%). Nuclear p53 immunoreactivity was observed in 6/21
      patients (28.6%), and all of them were type III tumors (6/8), compared with no
      p53 expression in type I (0/13), P=0.0002. p53 expression was also associated
      with high degree of cell proliferation (Ki-67-positive nuclear cells), P=0.00001.
      Bcl-2 expression was either unreactive or weakly positive in all tumor lesions.
      The mean follow-up period was 50.4 months (SD=45.2), varying from 6 to 144
      months. Overall survival time of patients with positive p53 expression and high
      proliferative rate was significantly lower than that of negative patients (14.4
      vs 123 months, P=0.0007). CONCLUSIONS: (i) p53 immunoexpression associated with
      high proliferative rate was useful to distinguish between type I and type III
      gastric carcinoid tumors and (ii) these markers were able to predict a shorter
      survival.

PMID- 17206074
TI  - Gastric electrical stimulation in medically refractory nausea and vomiting.
AB  - INTRODUCTION: High-frequency gastric electrical stimulation is a new therapeutic
      option to improve refractory nausea and vomiting, in gastroparetic patients. Its
      effects on gastric emptying are, however, inconstant and limited. Therefore, we
      have hypothesized that high-frequency gastric electrical stimulation could be
      also effective in patients suffering from refractory vomiting and nausea with
      normal gastric emptying, and we have compared the symptomatic efficacy of high
      frequency gastric electrical stimulation between patients with delayed and normal
      gastric emptying. PATIENTS AND METHODS: Fifteen patients with chronic, severe and
      medically resistant nausea and vomiting were included in the study. Gastric
      emptying was delayed in eight patients (Group 1) and normal in seven patients
      (Group 2). At inclusion and at 6 months after the start of the stimulation,
      symptoms (nausea and vomiting, bloating, regurgitations, abdominal pain and
      appetite) and quality of life were prospectively evaluated using the
      Gastrointestinal Quality of Life Index score whereas gastric emptying was
      assessed by scintigraphy and/or octanoic acid breath test. RESULTS: Age, sex,
      symptoms and quality of life were not different at baseline between the two
      groups. At 6 months, Gastrointestinal Quality of Life Index and nausea/vomiting
      scores had significantly improved in both groups. Other symptoms (bloating,
      regurgitations, abdominal pain and appetite) had improved at 6 months in Group 1
      but not in Group 2. Six months after the start of stimulation, gastric emptying
      was normal in 4/8 Group 1 patients and 5/7 Group 2 patients but was not
      significantly different from that calculated before the implantation of the
      stimulator. CONCLUSION: Our results suggest that high-frequency gastric
      electrical stimulation could be an effective therapy for treating chronic, severe
      vomiting and nausea whether gastric emptying is delayed or not.

PMID- 17206075
TI  - Diagnostic yield of routine duodenal biopsies in iron deficiency anaemia: a study
      from Western Anatolia.
AB  - OBJECTIVE: The role of routine endoscopic duodenal biopsies obtained during the
      evaluation of iron deficiency anaemia is being increasingly emphasized, but
      insufficiently applied. Diagnostic yield of this practice, mainly identification
      of coeliac disease, differs in different populations and geographic regions. The
      aim of this study is to assess the usefulness of routine duodenal biopsies during
      upper endoscopy in patients presenting with iron deficiency anaemia in Western
      Anatolia. METHODS: Routine duodenal biopsies were evaluated over a 12-month
      period in 100 consecutive adult patients with iron deficiency anaemia undergoing
      upper endoscopy. All potential bleeding lesions were identified and gastric as
      well as duodenal biopsies were taken for histopathologic investigation. RESULTS:
      A bleeding lesion is identified in 44% of cases. Duodenal biopsy gives an
      additional 5% diagnostic yield and revealed three patients with coeliac disease
      and two patients with giardiasis. One of the patients diagnosed with coeliac
      disease had a second bleeding lesion at the upper endoscopic examination.
      Appearance of the duodenal mucosa was normal in all patients including those with
      diagnostic duodenal biopsy. CONCLUSIONS: Routine duodenal sampling during the
      upper endoscopic examination gives an additional 5% diagnostic benefit and this
      practice should be included in the diagnostic work-up of patients with iron
      deficiency anaemia. As one of the patients who was found to have coeliac disease
      had a second bleeding lesion that may otherwise explain iron deficiency anaemia,
      finding a source for bleeding at the upper endoscopy should not preclude duodenal
      biopsy. Moreover, performing duodenal biopsy is still necessary even though the
      endoscopic appearance of the mucosa is normal. Aside from coeliac disease,
      Giardia infestation could be identified as a contributory factor for iron
      deficiency anaemia, in endemic regions.

PMID- 17206076
TI  - High prevalence of celiac disease in Brazilian blood donor volunteers based on
      screening by IgA antitissue transglutaminase antibody.
AB  - OBJECTIVE: To study the prevalence of celiac disease among blood donor volunteers
      based on screening by IgA antitissue transglutaminase antibody, followed by a
      confirmatory small intestine biopsy. METHODS: The transversal study involved 3000
      potential blood donors, residing in the city of Sao Paulo, Brazil. The
      participants were gender divided into 1500 men and 1500 women, with an average
      age 34.4+/-10.8 years, and included blood donor volunteers who could be turned
      down owing to anemia. All participants answered a questionnaire concerning the
      presence of diarrhea, constipation or abdominal pain during the 3 months before
      the study. Each participant with human recombinant IgA antitissue
      transglutaminase antibody level above 10 U/ml was invited to undergo a small
      intestine biopsy by means of an upper gastrointestinal endoscopy. The presence of
      villous atrophy and a positive antibody test were suggestive of possible celiac
      disease. RESULTS: Antitissue transglutaminase antibody was positive in 1.5%
      (45/3000) of the study population. Among the antibody-positive group, 21 (46.6%)
      agreed to have a biopsy performed, and within them the histological pattern of
      villous atrophy was confirmed in 66.7% (14/21). Consequently, the suggestive
      prevalence of celiac disease was at the minimum, one per 214 of the potential
      blood donor volunteers. A significant association was found between celiac
      disease and the symptoms of diarrhea, constipation and abdominal pain.
      CONCLUSIONS: The prevalence of celiac disease in Sao Paulo city is high and
      comparable to that observed in European countries. It is possible that in Brazil
      the prevalence of this disease had previously been underestimated.

PMID- 17206077
TI  - National survey of anticoagulation policy in endoscopy.
AB  - BACKGROUND: Anticoagulated patients who need to undergo endoscopy present unique
      challenges to the gastroenterologist. The continuation of anticoagulant therapy
      increases the risk of haemorrhagic complications of gastrointestinal endoscopy.
      Reversing the anticoagulation increases the risk of thromboembolism. In our
      experience in various endoscopy units, there are variable policies on the
      management of anticoagulated patients undergoing gastrointestinal endoscopy.
      METHODS: To study the current practice, survey questionnaires were sent to 2320
      doctors, working in 231 hospitals across the United Kingdom. RESULTS: Responses
      were obtained from 219 hospitals (94.8%), but only from 434 doctors (18.7%). The
      results show 40.8% endoscopists continued the patients on warfarin when
      performing a planned upper gastrointestinal endoscopy, whereas 26% stopped it;
      33.2% gave varying reports, that is, they used their own judgement according to
      the disease for which the anticoagulant was being given. For planned lower
      gastrointestinal endoscopy, 48.7% doctors preferred to stop warfarin; 53.3% of
      the endoscopists stated that they have a policy in place at their hospital for
      both upper and lower gastrointestinal endoscopy in anticoagulated patients; 5.5%
      had a policy for upper gastrointestinal endoscopy only and 6.2% for lower
      gastrointestinal endoscopy only. Thirty-five per cent doctors reported that they
      did not have any standard policy. We compared the responses from within a
      hospital to see whether the doctors were uniformly aware of an existing policy in
      their hospital. For upper gastrointestinal endoscopy, the responses were the same
      (either yes or no) by 51% of the doctors, whereas they were different by 49%. For
      lower gastrointestinal endoscopies, the same response was given by 49% of the
      doctors, whereas 51% gave different answers. The poor response rate from the
      doctors, however, makes firm interpretation of the data difficult. CONCLUSIONS: A
      wide variation in practice is seen across the country. A robust national
      guideline to streamline the endoscopy practice in anticoagulated patients is
      needed.

PMID- 17206078
TI  - Oesophageal pH monitoring using the Bravo catheter-free radio capsule.
AB  - OBJECTIVES: Oesophageal pH monitoring is the current standard for the diagnosis
      of gastro-oesophageal reflux disease. The Bravo capsule allows 48-h monitoring
      without the need for a naso-oesophageal catheter. Our aim was to assess the Bravo
      capsule in terms of patient discomfort and interference with daily activities,
      and to determine if 48-h Bravo pH studies facilitate the diagnosis of gastro
      oesophageal reflux disease. METHODS: Ambulatory pH studies were performed at two
      hospitals using either the Bravo capsule (n=100) or a conventional naso
      oesophageal catheter (n=100). Participants were selected either for investigation
      of symptoms suggestive of gastro-oesophageal reflux disease, or to follow-up
      antireflux surgery. All participants completed questionnaires to assess
      discomfort and interference with daily activities. RESULTS: Eighty-nine Bravo
      studies recorded at least 48 h of data, and 95 were diagnostic. Bravo
      participants reported significantly less discomfort during insertion (P<0.0001)
      and monitoring (P<0.0001), and less interference with daily activities
      (P<0.0001), eating (P<0.005), sleeping (P<0.0001) and work (P<0.0001). No
      significant difference was observed between day 1 and 2 median total time pH<4
      (4.0 and 4.3%, P=0.64), erect time pH<4 (5.0 and 5.0%, P=0.56), supine time pH<4
      (0.5 and 0.5%, P=0.23), and Johnson-DeMeester scores (15.9 and 16.2, P=0.90). Ten
      Bravo participants (10%) were diagnosed with gastro-oesophageal reflux disease
      using day 2 data after a normal day 1. CONCLUSIONS: The Bravo capsule
      significantly reduces the patient discomfort and interference with normal daily
      activities during pH monitoring associated with a naso-oesophageal catheter.
      Moreover, 48-h Bravo studies offer an advantage over conventional 24-h studies in
      diagnosing gastro-oesophageal reflux disease.

PMID- 17206079
TI  - Impedance signature of pharyngeal gaseous reflux.
AB  - BACKGROUND: Pharyngeal impedance changes induced by various pharyngeal reflux
      events have not been characterized. OBJECTIVES: To characterize pharyngeal
      impedance changes induced by participant-perceived belching events. METHODS: We
      systematically evaluated pharyngeal impedance and pH changes related to 453 belch
      events in 11 gastroesophageal reflux disease, 10 reflux attributed-laryngitis
      patients and 16 controls. RESULTS: Of 453 belch events, 362 were analyzable. Of
      these, 72% occurred within 10 s, 93% within 20 s, 99% within 30 s and 100% within
      40 s of the time that participants marked a belch event. In 15% impedance changes
      in the pharynx preceded, in 12% they were simultaneous and in 73% they occurred
      after the start of the impedance change in the proximal esophagus. Time interval
      between the two events ranged between 0.4+/-0.03 and 0.7+/-0.1 s. In all, there
      were three types of belch-induced impedance changes: (a) impedance increase, (b)
      impedance decrease and (c) multiphasic. Twenty percent of impedance events
      associated with belching had less than 50% change from baseline, whereas in 51%
      changes exceeded or were equal to 50%. Among events with a drop in pharyngeal
      impedance, only two satisfied the criteria for the liquid reflux event.
      CONCLUSIONS: Pharyngeal ventilation of gastric gaseous content seems to have a
      unique impedance signature. During pharyngeal gas reflux events, impedance
      changes may start before or after proximal esophageal changes. Belching may
      induce negative pharyngeal changes that do not meet the criteria for liquid
      reflux. These findings need to be taken into consideration in the analysis of
      pharyngeal reflux events.

PMID- 17206080
TI  - Relationship between clinical features of Crohn's disease and the risk of
      developing extraintestinal manifestations.
AB  - OBJECTIVES: Crohn's disease is frequently associated with extraintestinal
      manifestations. The aim of this study was to evaluate the degree of association
      between the development of extraintestinal manifestations, the clinical forms of
      Crohn's disease according to the Vienna Classification and to the presence of
      several potential risk factors of the disease. METHODS: One hundred and seventy
      three consecutive Crohn's disease patients were studied. Sex, smoking habits,
      previous Crohn's disease-related surgery, family history of Crohn's disease,
      steroid dependency, steroid resistance and the presence of at least one mutant
      allele in any of the three considered variants of CARD15 gene were considered as
      potential risk factors. The Vienna Classification was applied, and the presence
      of extraintestinal manifestations was evaluated. RESULTS: A total of 61 (35.3%)
      patients developed extraintestinal manifestations. They were more frequently seen
      in women than in men (41.1 vs. 26.7%), (odds ratio 1.92, 95% confidence interval:
      0.99-3.70; P=0.05) and in steroid-dependent patients than in steroid responders
      (61.1 vs. 28.5%), (odds ratio 3.94, 95% confidence interval: 1.83-8.49; P<0.01).
      No relationship was found in general between the extraintestinal manifestations
      of Crohn's disease and smoking habits, previous Crohn's disease-related surgery,
      a family history of Crohn's disease, steroid resistance and CARD15 mutations.
      Such relationships were, however, detected for some individual extraintestinal
      manifestations as between both smoking habits (odds ratio 9.09, 95% confidence
      interval: 1.15-71.66; P<0.05) and the G908R CARD15 mutation (odds ratio 4.76, 95%
      confidence interval: 1.11-20.43; P<0.05), respectively, and erythema nodosum.
      Patients with any colonic involvement of Crohn's disease (L2+L3) suffered from
      extraintestinal manifestations of the disease more frequently than patients
      without colonic involvement (42.7 vs. 25.9%, respectively; odds ratio 2.12, 95%
      confidence interval: 1.10-4.07; P<0.05). CONCLUSIONS: Female gender, steroid
      dependency and colonic involvement are associated with the risk of developing
      extraintestinal manifestations of Crohn's disease.

PMID- 17206081
TI  - Peptic ulcer disease associated with Helicobacter felis in a dog owner.
AB  - The aim of this study was to investigate the identity of the Helicobacter
      heilmannii-like bacteria found in the stomach of a human patient suffering from
      stomach ulcers and her asymptomatic pet dog. An elderly woman was referred for
      gastroscopy because of right hypochondrial pain, nausea, anorexia and vomiting.
      Gastric ulcers were observed and histology revealed the presence of multiple H.
      heilmannii-like bacteria. Multiplex polymerase chain reaction (PCR) identified
      the bacteria as H. felis. Her pet dog was also examined gastroscopically. Only
      mild gastric lesions were found but PCR showed the presence of H. felis as well
      as H. bizzozeronii and Candidatus H. heilmannii. This report associates H. felis
      infection in humans with severe gastric ulceration. Moreover, the suggestion can
      be made that the patient contracted H. felis from her dog.

PMID- 17206082
TI  - Repeated coaxial colonic stenting in the palliative management of benign colonic
      obstruction.
AB  - In inflammatory bowel disease, strictures of the colon, causing bowel
      obstruction, is not uncommon. Usually an operative procedure can deal with these
      strictures. We describe a case of an unfit patient with pulmonary malignancy
      having a Crohn's stricture of the recto-sigmoid junction in which repeated
      coaxial placement of self-expanding metallic stents eliminated the need to
      perform an operation. This is the first report of multiple coaxial colonic
      stenting. It shows that there is a place for stents in selected cases of
      inflammatory bowel disease with a limited life expectancy and that repeated
      colonic stenting makes colonic stenting possible also in patients requiring
      stents for longer time periods.

PMID- 17206083
TI  - Juvenile polyposis of the stomach causing recurrent upper gastrointestinal
      bleeding.
AB  - We present the case of a 42-year-old man who suffered from recurrent severe upper
      gastrointestinal bleeding starting from February 2003. Endoscopy showed multiple
      glassy polyps in the stomach, which corresponded to a diffuse mucosal thickening
      detected by endosonography. The duodenum was normal. In February 2006, life
      threatening acute gastrointestinal bleeding prompted total gastrectomy. The
      resection specimen showed the gastric mucosa carpeted by numerous glassy
      pedunculated polyps, measuring 2 cm in largest diameter. Histologically, the
      polyps were characterized by an abundant loose stroma and by elongated, twisting
      foveolae, covered by hyperplastic epithelium. Colonoscopy including the terminal
      ileum revealed a single tubulovillous adenoma, but no hamartomatous polyps,
      rendering a final diagnosis of juvenile polyposis of the stomach. This case
      represents the first description of juvenile polyposis causing life-threatening
      gastric haemorrhage. Thus, although rare, the disease has to be considered in the
      differential diagnosis of patients with acute upper gastrointestinal tract
      bleeding.

PMID- 17206084
TI  - Treatment of hepatitis C virus-associated inflammatory polyneuropathy with
      pegylated interferon-alpha and ribavirin.
AB  - Peripheral neuropathy is common in patients with hepatitis C virus infection and
      cryoglobulinemia. Here, we report a patient with axonal polyneuropathy associated
      with type III mixed cryoglobulinemia and hepatitis C virus infection without
      significant liver disease, who was successfully treated with pegylated interferon
      alpha-2a and ribavirin. This case illustrated that clinical improvement was
      paralleled by a decrease of cryocrit but not necessarily by a decrease of viral
      replication rate. Treatment of hepatitis C virus-cryoglobulinemia-associated
      neuropathy should therefore be continued even if response of viral replication is
      lacking or delayed as long as a clinical benefit can be observed.

PMID- 17206085
TI  - The power of saying no.

PMID- 17206087
TI  - Implement a handoff communications approach.

PMID- 17206088
TI  - Compensation survey 2007.

PMID- 17206089
TI  - Improve your environment through communication and change.

PMID- 17206090
TI  - Encourage corporate compliance and disclosure.

PMID- 17206091
TI  - Nursing Management Visionary Leader 2006: North Carolina chief nurse officer
      earns journal's annual leadership award.
AB  - The following manuscript is the winning Visionary Leader 2006 entry submitted to
      Nursing Management by the staff of Moses Cone Health System, Greensboro, N.C., in
      recognition of Joan Wessman, chief nurse officer at the organization. Joan was
      formally recognized for her achievements during the opening ceremony of Congress
      2006, October 15, in Philadelphia, Pa., during which she received the award,
      sponsored this year by B.E. Smith.

PMID- 17206092
TI  - Patient safety: learning from the aviation industry.

PMID- 17206095
TI  - The "ambient experience": pediatric patients and diagnostic testing.

PMID- 17206096
TI  - Recognize the many facets of gerontological nursing.

PMID- 17206097
TI  - Massachusetts nurse leaders share best practices.
AB  - By using networking and collaboration between hospitals and staff members, the
      Massachusetts Magnet Networking Group helps regional organizations attain Magnet
      status while promoting high-quality nursing practices.

PMID- 17206098
TI  - Innovations in cardiac nursing and technology.

PMID- 17206099
TI  - Adopt outcomes-focused strategies into your practice.

PMID- 17206100
TI  - Look professional while motivating staff toward certification.

PMID- 17206101
TI  - Management of neglected joint contractures.
AB  - This review is based on the author's experience treating over 5,000 joint
      contractures of the lower limbs in developing countries in the tropics and
      subtropics over the past 40 years. It includes realistic methods of correction of
      neglected, untreated joint contractures mainly due to poliomyelitis and other
      paralytic conditions by general duty medical officers. Corrections were performed
      in centers where medical facilities were often limited and where millions of
      untreated patients still await treatment. The treatment includes percutaneous
      correction of flexed hips, knees and equinus ankles and rotational osteotomy of
      the distal femur for severe knee contractures. Surgery is followed by simple
      cheap braces made out of local materials. These methods will usually allow early
      mobility, and in severe cases survival instead of early death.

PMID- 17206102
TI  - Range of motion in anterior femoroacetabular impingement.
AB  - The range of motion of normal hips and hips with femoroacetabular impingement
      relative to some specific anatomic reference landmarks is unknown. We therefore
      described: (1) the range of motion pattern relative to landmarks; (2) the
      location of the impingement zones in normal and impinging hips; and (3) the
      influence of surgical debridement on the range of motion. We used a previously
      developed and validated noninvasive 3-D CT-based method for kinematic hip
      analysis to compare the range of motion pattern, the location of impingement, and
      the effect of virtual surgical reconstruction in 28 hips with anterior
      femoroacetabular impingement and a control group of 33 normal hips. Hips with
      femoroacetabular impingement had decreased flexion, internal rotation, and
      abduction. Internal rotation decreased with increasing flexion and adduction. The
      calculated impingement zones were localized in the anterosuperior quadrant of the
      acetabulum and were similar in the two groups and in impingement subgroups. The
      average improvement of internal rotation was 5.4 degrees for pincer hips, 8.5
      degrees for cam hips, and 15.7 degrees for mixed impingement. This method helps
      the surgeon quantify the severity of impingement and choose the appropriate
      treatment option; it provides a basis for future image-guided surgical
      reconstruction in femoroacetabular impingement with less invasive techniques.

PMID- 17206103
TI  - Cement restrictor function below the femoral isthmus.
AB  - Cement restrictors rely on achieving an interference fit with the wall of the
      medullary canal. Depending on the design of the cement restrictor, the
      intramedullary fit may be compromised as the femur starts to widen distally.
      Three different designs of cement restrictor were identified; universal, press
      fit, and expandable. We determined which design of cement restrictor could resist
      the greatest pressures in a closed column of cement. Additionally, we recorded
      leakage of cement past the restrictor. We reamed synthetic femora to recreate the
      normal distal flare of the femur below the femoral isthmus. After inserting the
      cement restrictor, low-viscosity cement was gradually pressurized using an
      electronically controlled pneumatic ram. We then simultaneously recorded cement
      pressure above the cement restrictor and displacement of the cement restrictor.
      There was variation in the performance of the cement restrictors. The expandable
      cement restrictors resisted the greatest pressures. The resorbable expandable
      (REX Cement Stop) and press-fit cement restrictors reliably prevented cement
      leakage. The press-fit and universal restrictors failed at low pressures when
      deployed below the isthmus. The choice of cement restrictor may need to be
      modified if preoperative templating indicates the restrictor will sit below the
      femoral isthmus.

PMID- 17206105
TI  - ARPP protein is selectively expressed in renal oncocytoma, but rarely in renal
      cell carcinomas.
AB  - We have recently isolated a gene, Ankyrin-repeated protein with a proline-rich
      region (ARPP), that is highly expressed in the skeletal and cardiac muscle. Our
      previous immunohistochemical analysis revealed that ARPP expression was augmented
      in rhabdomyosarcoma but scarcely detectable in leiomyosarcoma, showing that ARPP
      is a useful marker for rhabdomyosarcoma. In the present study, we generated the
      anti-ARPP monoclonal antibody, YAS11, immunoreactive with the N-terminal region
      (amino-acids residues 1-145) of the ARPP protein. Further, we
      immunohistochemically analyzed 100 renal tumors including 14 oncocytomas, and 86
      renal cell carcinomas (RCCs). We found that ARPP was highly expressed in 12 of
      the 14 (85.7%) oncocytomas, but was detectable in only four of the 86 (4.7%)
      RCCs. Interestingly, ARPP was not detected in any of 11 chromophobe RCCs,
      suggesting that ARPP may be useful for differential diagnosis between oncocytoma
      and chromophobe RCC. Furthermore, we found that ARPP was selectively expressed in
      part of the distal renal tubule in normal kidney. Immunoelectron microscopy with
      anti-ARPP antibody revealed that ARPP was localized in mitochondria and nuclei in
      both the normal distal renal tubule and oncocytoma, suggesting that oncocytoma
      may be derived from the distal nephron, and probably from part of the distal
      renal tubule.

PMID- 17206107
TI  - Nature medicine 2.0.

PMID- 17206106
TI  - Significance of lymph vessel invasion identified by the endothelial lymphatic
      marker D2-40 in node negative breast cancer.
AB  - Monoclonal antibody D2-40, a marker of lymphatic endothelium, identifies tumor
      emboli in lymph vessels. The aim of the study was to assess whether D2-40+ lymph
      vessel invasion (LVI) correlates with clinicopathologic factors including
      lymphovascular invasion (LVI) as assessed by haematoxylin and eosin-stained
      sections (H&E+ or H&E-) and to assess the prognostic significance in node
      negative breast cancer. The study group consisted of 303 node-negative breast
      cancer patients that had a median follow-up of 7.6 years. Clinical and
      pathological data were retrieved from the Henrietta Banting database.
      Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded
      tissue sections of the primary invasive carcinoma using D2-40. Immunostaining
      with CD31 was performed on the discordant cases that were H&E+/D2-40-. D2-40+
      lymph vessel invasion was detected in 82/303 (27%) cases. The foci of lymphatic
      invasion occurred predominantly at the invasive front of the tumor. The absence
      of D2-40 and CD31 in 13/17 discordant cases was suggestive of retraction
      artefact. D2-40+ lymph vessel invasion correlated significantly with age
      (P=0.0003), tumor size (P=0.005), histological grade (P=0.0001), H&E+ (P=<0.0001)
      and estrogen receptor status (P=0.005) but not with histological type or
      progesterone receptor status. Multivariate analysis revealed that D2-40+ lymph
      vessel invasion was the only significant predictor of distant recurrence. There
      was no significant association between D2-40 status and local recurrence
      (P=0.752) or regional recurrence (P=0.13). Both D2-40+lymph vessel invasion
      (P=0.009) and H&E+LVI cases (P=0.02) were associated with overall shorter
      survival in univariate analysis. These data indicate that D2-40 identifies
      lymphatic invasion in breast tumors and is a significant predictor of outcome in
      breast cancer.

PMID- 17206108
TI  - Biomarkers trump behavior in mental illness diagnosis.

PMID- 17206109
TI  - Alternative medicine loses its champion.

PMID- 17206111
TI  - Abstinence activist to head US family planning.

PMID- 17206112
TI  - Companies balk at California's patent rules for stem cell research.

PMID- 17206113
TI  - Practical malaria tests promise results in remote regions.

PMID- 17206114
TI  - Menno de Jong.

PMID- 17206116
TI  - Cluster busters.

PMID- 17206117
TI  - In reply to 'Cardiotoxicity of the cancer therapeutic agent imatinib mesylate'.

PMID- 17206118
TI  - In reply to 'Cardiotoxicity of the cancer therapeutic agent imatinib mesylate'.

PMID- 17206119
TI  - In reply to 'Cardiotoxicity of the cancer therapeutic agent imatinib mesylate'.

PMID- 17206121
TI  - In reply to 'Cardiotoxicity of the cancer therapeutic agent imatinib mesylate'.

PMID- 17206122
TI  - Is leptin an important physiological regulator of CRP?

PMID- 17206123
TI  - Is leptin an important physiological regulator of CRP?

PMID- 17206124
TI  - Is leptin an important physiological regulator of CRP?

PMID- 17206127
TI  - Bone-breaking cancer treatment.

PMID- 17206128
TI  - IL-23: a master regulator in Crohn disease.

PMID- 17206129
TI  - Scanning the genome.

PMID- 17206130
TI  - A 'good death' for tumor immunology.

PMID- 17206131
TI  - Hope in sight for retinoblastoma.

PMID- 17206132
TI  - Bad signals jam organelle traffic.

PMID- 17206133
TI  - Singling out heart cells.

PMID- 17206138
TI  - Isolation of amniotic stem cell lines with potential for therapy.
AB  - Stem cells capable of differentiating to multiple lineages may be valuable for
      therapy. We report the isolation of human and rodent amniotic fluid-derived stem
      (AFS) cells that express embryonic and adult stem cell markers. Undifferentiated
      AFS cells expand extensively without feeders, double in 36 h and are not
      tumorigenic. Lines maintained for over 250 population doublings retained long
      telomeres and a normal karyotype. AFS cells are broadly multipotent. Clonal human
      lines verified by retroviral marking were induced to differentiate into cell
      types representing each embryonic germ layer, including cells of adipogenic,
      osteogenic, myogenic, endothelial, neuronal and hepatic lineages. Examples of
      differentiated cells derived from human AFS cells and displaying specialized
      functions include neuronal lineage cells secreting the neurotransmitter L
      glutamate or expressing G-protein-gated inwardly rectifying potassium channels,
      hepatic lineage cells producing urea, and osteogenic lineage cells forming tissue
      engineered bone.

PMID- 17206139
TI  - Cyclostreptin binds covalently to microtubule pores and lumenal taxoid binding
      sites.
AB  - Cyclostreptin (1), a natural product from Streptomyces sp. 9885, irreversibly
      stabilizes cellular microtubules, causes cell cycle arrest, evades drug
      resistance mediated by P-glycoprotein in a tumor cell line and potently inhibits
      paclitaxel binding to microtubules, yet it only weakly induces tubulin assembly.
      In trying to understand this paradox, we observed irreversible binding of
      synthetic cyclostreptin to tubulin. This results from formation of covalent
      crosslinks to beta-tubulin in cellular microtubules and microtubules formed from
      purified tubulin in a 1:1 total stoichiometry distributed between Thr220 (at the
      outer surface of a pore in the microtubule wall) and Asn228 (at the lumenal
      paclitaxel site). Unpolymerized tubulin was only labeled at Thr220. Thus, the
      pore region of beta-tubulin is an undescribed binding site that (i) elucidates
      the mechanism by which taxoid-site compounds reach the kinetically unfavorable
      lumenal site and (ii) explains how taxoid-site drugs induce microtubule formation
      from dimeric and oligomeric tubulin.

PMID- 17206140
TI  - Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp
      recording study.
AB  - Basal dendrites receive the majority of synapses that contact neocortical
      pyramidal neurons, yet our knowledge of synaptic processing in these dendrites
      has been hampered by their inaccessibility for electrical recordings. A new
      approach to patch-clamp recordings enabled us to characterize the integrative
      properties of these cells. Despite the short physical length of rat basal
      dendrites, synaptic inputs were electrotonically remote from the soma (>30-fold
      excitatory postsynaptic potential (EPSP) attenuation) and back-propagating action
      potentials were significantly attenuated. Unitary EPSPs were location dependent,
      reaching large amplitudes distally (>8 mV), yet their somatic contribution was
      relatively location independent. Basal dendrites support sodium and NMDA spikes,
      but not calcium spikes, for 75% of their length. This suggests that basal
      dendrites, despite their proximity to the site of action potential initiation, do
      not form a single basal-somatic region but rather should be considered as a
      separate integrative compartment favoring two integration modes: subthreshold,
      location-independent summation versus local amplification of incoming
      spatiotemporally clustered information.

PMID- 17206141
TI  - Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive
      evolution.
AB  - We recently described an association between risk of type 2diabetes and variants
      in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a
      population attributable risk (PAR) of 17%-28% in three populations of European
      ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk
      variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through
      replication in West African and Danish type 2 diabetes case-control studies and
      an expanded Icelandic study. We also identify another variant of the same gene,
      HapA, that shows evidence of positive selection in East Asian, European and West
      African populations. Notably, HapA shows a suggestive association with body mass
      index and altered concentrations of the hunger-satiety hormones ghrelin and
      leptin in males, indicating that the selective advantage of HapA may have been
      mediated through effects on energy metabolism.

PMID- 17206142
TI  - Common genetic variants account for differences in gene expression among ethnic
      groups.
AB  - Variation in DNA sequence contributes to individual differences in quantitative
      traits, but in humans the specific sequence variants are known for very few
      traits. We characterized variation in gene expression in cells from individuals
      belonging to three major population groups. This quantitative phenotype differs
      significantly between European-derived and Asian-derived populations for 1,097 of
      4,197 genes tested. For the phenotypes with the strongest evidence of cis
      determinants, most of the variation is due to allele frequency differences at cis
      linked regulators. The results show that specific genetic variation among
      populations contributes appreciably to differences in gene expression phenotypes.
      Populations differ in prevalence of many complex genetic diseases, such as
      diabetes and cardiovascular disease. As some of these are probably influenced by
      the level of gene expression, our results suggest that allele frequency
      differences at regulatory polymorphisms also account for some population
      differences in prevalence of complex diseases.

PMID- 17206143
TI  - Systematic pathway analysis using high-resolution fitness profiling of
      combinatorial gene deletions.
AB  - Systematic genetic interaction studies have illuminated many cellular processes.
      Here we quantitatively examine genetic interactions among 26 Saccharomyces
      cerevisiae genes conferring resistance to the DNA-damaging agent methyl
      methanesulfonate (MMS), as determined by chemogenomic fitness profiling of pooled
      deletion strains. We constructed 650 double-deletion strains, corresponding to
      all pairings of these 26 deletions. The fitness of single- and double-deletion
      strains were measured in the presence and absence of MMS. Genetic interactions
      were defined by combining principles from both statistical and classical
      genetics. The resulting network predicts that the Mph1 helicase has a role in
      resolving homologous recombination-derived DNA intermediates that is similar to
      (but distinct from) that of the Sgs1 helicase. Our results emphasize the utility
      of small molecules and multifactorial deletion mutants in uncovering functional
      relationships and pathway order.

PMID- 17206144
TI  - A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of
      cerebral infarction.
AB  - Cerebral infarction is the most common type of stroke and often causes long-term
      disability. To investigate the genetic contribution to cerebral infarction, we
      conducted a case-control study using 52,608 gene-based tag SNPs selected from the
      JSNP database. Here we report that a nonsynonymous SNP in a member of protein
      kinase C (PKC) family, PRKCH, was significantly associated with lacunar
      infarction in two independent Japanese samples (P = 5.1 x 10(-7), crude odds
      ratio of 1.40). This SNP is likely to affect PKC activity. Furthermore, a 14-year
      follow-up cohort study in Hisayama (Fukuoka, Japan) supported involvement of this
      SNP in the development of cerebral infarction (P = 0.03, age- and sex-adjusted
      hazard ratio of 2.83). We also found that PKCeta was expressed mainly in vascular
      endothelial cells and foamy macrophages in human atherosclerotic lesions, and its
      expression increased as the lesion type progressed. Our results support a role
      for PRKCH in the pathogenesis of cerebral infarction.

PMID- 17206145
TI  - CNS myeloid DCs presenting endogenous myelin peptides 'preferentially' polarize
      CD4+ T(H)-17 cells in relapsing EAE.
AB  - Peripherally derived CD11b(+) myeloid dendritic cells (mDCs), plasmacytoid DCs,
      CD8alpha(+) DCs and macrophages accumulate in the central nervous system during
      relapsing experimental autoimmune encephalomyelitis (EAE). During acute relapsing
      EAE induced by a proteolipid protein peptide of amino acids 178-191, transgenic T
      cells (139TCR cells) specific for the relapse epitope consisting of proteolipid
      protein peptide amino acids 139-151 clustered with mDCs in the central nervous
      system, were activated and differentiated into T helper cells producing
      interleukin 17 (T(H)-17 cells). CNS mDCs presented endogenously acquired peptide,
      driving the proliferation of and production of interleukin 17 by naive 139TCR
      cells in vitro and in vivo. The mDCs uniquely biased T(H)-17 and not T(H)1
      differentiation, correlating with their enhanced expression of transforming
      growth factor-beta1 and interleukins 6 and 23. Plasmacytoid DCs and CD8alpha(+)
      DCs were superior to macrophages but were much less efficient than mDCs in
      presenting endogenous peptide to induce T(H)-17 cells. Our findings indicate a
      critical function for CNS mDCs in driving relapses in relapsing EAE.

PMID- 17206146
TI  - B and T lymphocyte attenuator regulates CD8+ T cell-intrinsic homeostasis and
      memory cell generation.
AB  - B and T lymphocyte attenuator (BTLA) is a negative regulator of T cell
      activation, but its function in vivo is not well characterized. Here we show that
      mice deficient in full-length BTLA or its ligand, herpesvirus entry mediator, had
      increased number of memory CD8(+) T cells. The memory CD8(+) T cell phenotype
      resulted from a T cell-intrinsic perturbation of the CD8(+) T cell pool. Naive
      BTLA-deficient CD8(+) T cells were more efficient than wild-type cells at
      generating memory in a competitive antigen-specific system. This effect was
      independent of the initial expansion of the responding antigen-specific T cell
      population. In addition, BTLA negatively regulated antigen-independent
      homeostatic expansion of CD4(+) and CD8(+) T cells. These results emphasize two
      central functions of BTLA in limiting T cell activity in vivo.

PMID- 17206147
TI  - Direct interactions between NEDD8 and ubiquitin E2 conjugating enzymes upregulate
      cullin-based E3 ligase activity.
AB  - Although cullin-1 neddylation is crucial for the activation of SCF ubiquitin E3
      ligases, the underlying mechanisms for NEDD8-mediated activation of SCF remain
      unclear. Here we demonstrate by NMR and mutational studies that NEDD8 binds the
      ubiquitin E2 (UBC4), but not NEDD8 E2 (UBC12). Our data imply that NEDD8 forms an
      active platform on the SCF complex for selective recruitment of ubiquitin-charged
      E2s in collaboration with RBX1, and thereby upregulates the E3 activity.

PMID- 17206148
TI  - Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal
      aneuploidy detection.
AB  - Current methods for prenatal diagnosis of chromosomal aneuploidies involve the
      invasive sampling of fetal materials using procedures such as amniocentesis or
      chorionic villus sampling and constitute a finite risk to the fetus. Here, we
      outline a strategy for fetal chromosome dosage assessment that can be performed
      noninvasively through analysis of placental expressed mRNA in maternal plasma. We
      achieved noninvasive prenatal diagnosis of fetal trisomy 21 by determining the
      ratio between alleles of a single-nucleotide polymorphism (SNP) in PLAC4 mRNA,
      which is transcribed from chromosome 21 and expressed by the placenta, in
      maternal plasma. PLAC4 mRNA in maternal plasma was fetal derived and cleared
      after delivery. The allelic ratios in maternal plasma correlated with those in
      the placenta. Fetal trisomy 21 was detected noninvasively in 90% of cases and
      excluded in 96.5% of controls.

PMID- 17206149
TI  - Tropism of avian influenza A (H5N1) in the upper and lower respiratory tract.
AB  - Poor human-to-human transmission of influenza A H5N1 virus has been attributed to
      the paucity of putative sialic acid alpha2-3 virus receptors in the epithelium of
      the human upper respiratory tract, and thus to the presumed inability of the
      virus to replicate efficiently at this site. We now demonstrate that ex vivo
      cultures of human nasopharyngeal, adenoid and tonsillar tissues can be infected
      with H5N1 viruses in spite of an apparent lack of these receptors.

PMID- 17206150
TI  - Detection of minor drug-resistant populations by parallel allele-specific
      sequencing.
AB  - We developed a highly sensitive parallel allele-specific sequencing (PASS) assay
      to simultaneously analyze a large number of viral genomes and detect minor drug
      resistant populations at approximately 0.1-0.01% levels. Using this assay on
      samples from individuals infected with human immunodeficiency viruses (HIV), we
      successfully detected and quantified minor populations of drug-resistant viruses
      and performed linkage analysis of multiple-drug resistance mutations. This assay
      may serve as a useful tool to study drug resistance in HIV and other infectious
      agents.

PMID- 17206151
TI  - Mining a yeast library for brain endothelial cell-binding antibodies.
AB  - We describe the use of yeast surface display for the identification of antibodies
      that bind the plasma membranes of living cells. Yeast panning with a nonimmune
      human single-chain antibody library identified 34 unique lead antibodies that
      bind (K(d) = 82 +/- 15 nM) and in some cases internalize into rat brain
      endothelial cells. In addition, we used a new yeast display immunoprecipitation
      procedure for initial characterization of the cognate antigens.

PMID- 17206152
TI  - Rapid identification of functionally critical amino acids in a G protein-coupled
      receptor.
AB  - G protein-coupled receptors (GPCRs) comprise one of the largest protein families
      found in nature. Here we describe a new experimental strategy that allows rapid
      identification of functionally critical amino acids in the rat M(3) muscarinic
      acetylcholine receptor (M3R), a prototypic class I GPCR. This approach involves
      low-frequency random mutagenesis of the entire M3R coding sequence, followed by
      the application of a new yeast genetic screen that allows the recovery of
      inactivating M3R single point mutations. The vast majority of recovered mutant
      M3Rs also showed substantial functional impairments in transfected mammalian (COS
      7) cells. A subset of mutant receptors, however, behaved differently in yeast and
      mammalian cells, probably because of the specific features of the yeast
      expression system used. The screening strategy described here should be
      applicable to all GPCRs that can be expressed functionally in yeast.

PMID- 17206153
TI  - Cosmology: the Universe's skeleton sketched.

PMID- 17206154
TI  - Dark matter maps reveal cosmic scaffolding.
AB  - Ordinary baryonic particles (such as protons and neutrons) account for only one
      sixth of the total matter in the Universe. The remainder is a mysterious 'dark
      matter' component, which does not interact via electromagnetism and thus neither
      emits nor reflects light. As dark matter cannot be seen directly using
      traditional observations, very little is currently known about its properties. It
      does interact via gravity, and is most effectively probed through gravitational
      lensing: the deflection of light from distant galaxies by the gravitational
      attraction of foreground mass concentrations. This is a purely geometrical effect
      that is free of astrophysical assumptions and sensitive to all matter--whether
      baryonic or dark. Here we show high-fidelity maps of the large-scale distribution
      of dark matter, resolved in both angle and depth. We find a loose network of
      filaments, growing over time, which intersect in massive structures at the
      locations of clusters of galaxies. Our results are consistent with predictions of
      gravitationally induced structure formation, in which the initial, smooth
      distribution of dark matter collapses into filaments then into clusters, forming
      a gravitational scaffold into which gas can accumulate, and stars can be built.

PMID- 17206155
TI  - Escape from HER-family tyrosine kinase inhibitor therapy by the kinase-inactive
      HER3.
AB  - Oncogenic tyrosine kinases have proved to be promising targets for the
      development of highly effective anticancer drugs. However, tyrosine kinase
      inhibitors (TKIs) against the human epidermal growth factor receptor (HER) family
      show only limited activity against HER2-driven breast cancers, despite effective
      inhibition of epidermal growth factor receptor (EGFR) and HER2 in vivo. The
      reasons for this are unclear. Signalling in trans is a key feature of this
      multimember family and the critically important phosphatidylinositol-3-OH kinase
      (PI(3)K)/Akt pathway is driven predominantly through transphosphorylation of the
      kinase-inactive HER3 (refs 9, 10). Here we show that HER3 and consequently
      PI(3)K/Akt signalling evade inhibition by current HER-family TKIs in vitro and in
      tumours in vivo. This is due to a compensatory shift in the HER3 phosphorylation
      dephosphorylation equilibrium, driven by increased membrane HER3 expression
      driving the phosphorylation reaction and by reduced HER3 phosphatase activity
      impeding the dephosphorylation reaction. These compensatory changes are driven by
      Akt-mediated negative-feedback signalling. Although HER3 is not a direct target
      of TKIs, HER3 substrate resistance undermines their efficacy and has thus far
      gone undetected. The experimental abrogation of HER3 resistance by small
      interfering RNA knockdown restores potent pro-apoptotic activity to otherwise
      cytostatic HER TKIs, re-affirming the oncogene-addicted nature of HER2-driven
      tumours and the therapeutic promise of this oncoprotein target. However, because
      HER3 signalling is buffered against an incomplete inhibition of HER2 kinase, much
      more potent TKIs or combination strategies are required to silence oncogenic HER2
      signalling effectively. The biologic marker with which to assess the efficacy of
      HER TKIs should be the transphosphorylation of HER3 rather than
      autophosphorylation.

PMID- 17206160
TI  - [The new law against smoking: success for public health?].

PMID- 17206161
TI  - [A survey of residential care services for HIV infected individuals].
AB  - The aims of this study were to examine the current situation regarding
      residential care facilities for HIV-infected individuals in Italy and to describe
      the characteristics of residents of such facilities.

PMID- 17206162
TI  - [Day surgery for cataract: descriptive survey in central and southern Italy].
AB  - Day surgery has rapidly gained worldwide acceptance especially in the field of
      ophthalmology. In Italy, cataract surgery is the most frequently performed
      surgical procedure, even on account of the ageing of the population. This
      procedure represents a very sensitive indicator of trends in day surgery
      hospitalizations and of political-managerial situations in the different regional
      healthcare realities. The aim of this study was to evaluate the diffusion of
      cataract day surgery in ophthalmology centres/divisions in central and southern
      Italy in 2003. A questionnaire was used to collect information regarding the
      number of surgical procedures performed, types of hospital admissions, time since
      the introduction of cataract day surgery, perioperative norms, and presence of
      other operative surgical centres in the area.

PMID- 17206163
TI  - [Evidence-based prevention: a new model for public health].
AB  - The concept of evidence-based prevention (EBP), was developed during the last
      decade as the counterpart, in Public Health, of Evidence-Based Medicine (EBM) in
      Clinical Medicine. The growing debate on EBP reflects the increasing recognition
      that successful evaluation of public health interventions will necessarily entail
      the use of research designs other than controlled trials as well as the use of
      various other types of evidence, often in combination. Evidence-based prevention,
      therefore, aims to implement those prevention strategies that have been found to
      be useful and effective through a formal evaluation based on scientific
      methodology. A the same it aims to progressively discard all preventive practices
      for which usefulness and effectiveness have not been proved.

PMID- 17206164
TI  - [Food labelling and the role of citizens: reading a food label. Note 2].
AB  - This review discusses European and Italian regulations concerning labelling of
      commercial beef (whether packed or not) and highlights their salient points in
      order to define criteria for correct beef labelling.

PMID- 17206165
TI  - [Prescription drugs and the elderly: results of the Argento study].
AB  - OBJECTIVE: To evaluate prescription drug use in the elderly and in particular, to
      determine the number and types of medications taken, whether and to what extent
      drugs that are contraindicated in this age group are being used, and what type of
      prescription check may be performed by primary care physicians. DESIGN: A survey
      was performed in a sample of non-institutionalised elderly subjects (= 65 years).
      These were selected by cluster sampling in 11 of 20 Italian regions and were
      interviewed in the home by trained interviewers using a standardised
      questionnaire. RESULTS: Eighty-seven percent of interviewed subjects reported
      that they had taken at least one medication in the previous year; higher
      frequencies were found in age groups= 75 years. The most common therapeutic
      classes of drugs used in all participating regions, in the previous week, were
      cardiovascular, gastrointestinal, metabolic (including drugs to treat diabetes)
      and nervous system. Among interviewed subjects, 45.3% reported using 4 or more
      different drugs, though wide regional differences were observed (Campania 60.5%,
      Bolzano 35.6%); 7.2 % were taking potentially inappropriate drugs while 2.3% were
      taking medications that may lead to potentially harmful interactions. In
      addition, 84.9% of subjects reported that their primary care physician regularly
      checked their drug prescriptions. CONCLUSIONS: The high frequency of prescription
      drug use observed in the elderly is a diffuse phenomenon, related to the
      worsening health conditions that inevitably accompany aging. Considering the
      extent of this phenomenon, care should be taken to improve qualitative (i.e.
      contraindications in the elderly, potential drug-interactions) and quantitative
      (high number of medications taken by the elderly) appropriateness in physician
      prescribing. In addition, special attention must be placed on regularly checking
      drug therapies in the elderly.

PMID- 17206166
TI  - [A retrospective study to an evaluation of the quality of Uniform Hospital
      Discharge Data Set regarding discharge with death of the patient attributed to a
      Diagnosis Related Group with a low Relative Weight; retrospective study in some
      hospitals in Rome [corrected]].
AB  - Aim of the present study is to evaluate the quality of medical record and Uniform
      Hospital Discharge Data Set (UHDDS), regarding admissions with death of the
      patient assigned to a Diagnosis Related Group (DRG) with a Relative Weight (RW)
      less than 1; the authors suggest that these admissions involve a more expensive
      hospital treatment if compared to admissions with favorable outcome and,
      therefore, the attribution of a DRG with RW more than 1 might be ascribed to an
      incorrect compilation of UHDDS. The admissions with the death of the patient,
      carried out between July 2002 and December 2002, in 11 different Rome hospitals
      located within the territory of two Local Health Units, have been split into 2
      groups: admissions assigned to a DRG with RW less than 1 (group 1) and more than
      1 (group 2). Afterward, two doctors of the Regional System of External Controls
      have required and examined the medical records of the group 1 (n= 57) using an
      evaluating format to verify the accuracy of UHDDS information. In the 91.0%
      (n=51) of the cases the UHDDS coding have been considered inadequate. In the
      96.2% of the cases (n=49) the principal diagnosis has not been correctly coded
      while, in the 69.2% of the cases (n=36), at least one of the secondary diagnosis
      has been incorrectly reported. Medium RW rose from 0,7893 to 1,4354 after
      controllers' review and assignment of the new DRG. The results have confirmed the
      initial hypothesis and pointed out how an incorrect compilation of the UHDDS
      might compromise its validity under a statistic and epidemiologic point of view
      and produce significant repercussions under the economic one.

PMID- 17206167
TI  - [The role of selected risk factors in three chronic degenerative conditions].
AB  - The aim of this study was to verify the possible effects that several of the most
      common endogenous and exogenous risk factors may have on the development of
      essential hypertension, hypercholesterolemia and type I diabetes. The study was
      performed on a national sample of the population aged 16-65 years. The study
      population was classified on the basis of health status, main life habits and
      family history. The relative risk of various exposures in healthy and ill
      subjects was evaluated as well as the population inference for the probability of
      developing disease. Though the proportion of ill subjects, especially diabetics,
      was low, the evaluated risk factors play an important role in most cases of
      chronic morbidity in patients over 40 years of age.

PMID- 17206168
TI  - [How Italian midwives contribute to breastfeeding promotion: a national
      experience of "cascade" training].
AB  - Social changes of the last century have increasingly transformed maternity and
      newborn care into a medical act and have greatly reduced the number of
      breastfeeding women. In Italy, the explicit aim of the Ministry of Health
      concerning mother and child health (Progetto-Obiettivo Materno-Infantile) is to
      bring this process back to a more natural activity. The prevalence of women who
      breastfed after the third month of life has been set as an indicator of the
      effectiveness of mother and child health services. However, the percentage of
      fully breastfeeding women at the fourth month of the newborn varies greatly among
      Italian regions, from 18 to 56%. As in many other Countries in the European
      Union, in Italy the initial education of the mother and child caregivers often
      lacks a specific formal training on breastfeeding promotion, as do academic
      midwife-training courses. In 2004 the Italian Federation of the Colleges of
      Midwives implemented a cascade training project in collaboration with the
      Istituto Superiore di Sanita, to train trainer-midwives who in turn would train
      midwives, either already working (Continuing Medical Education) or during their
      formal academic education. Contents, techniques and methods have been the same as
      those adopted for the World Health Organization's 40+40 hours course
      "Breastfeeding: counselling: a training course" for trainers. A total of 39
      training coordinators and teachers of academic midwifery courses have
      participated, in two separate groups. In their turn, the trainers have trained 74
      working midwives, from almost every Italian region. Throughout the training
      program, the trainers were supervised by two tutors who assessed their learning
      teaching performance and provided a final certificate. The program allowed the
      trainers and the other participants to reach a standard level of knowledge on the
      issue, regardless of their initial knowledge. Moreover, it helped to build and
      share a common language and attitude on the protection, promotion and support of
      breastfeeding. In the original course the final certification was not included;
      it was introduced in the present course to ensure high qualitative levels of
      teaching and to let the training groups better integrate with already existing
      training groups within the Local Health Authorities. To translate the training
      experience into an effective improvement of health objectives, as much as
      possible caregivers should be exposed to this kind of courses, from the beginning
      of their training. The WHO/UNICEF model proved to be a good basic model even for
      academic education, maybe with some additional elements aimed at the specific
      professionals. At present about half of the courses for midwives throughout Italy
      employ at least one teacher who is also in charge of the WHO/UNICEF course.

PMID- 17206169
TI  - [Evolution and current tools of multidimensional assessment in Italy].
AB  - Evaluation of the health status of elderly patients clearly should take into
      consideration the older individual's medical (physical and mental health),
      psychosocial and economical status, and functional capabilities and problems
      (multidimensional evaluation). This methodology has been used in anglo-saxon
      countries since over 20 years and is now quite diffuse in Italy as well. This
      paper reports the results of a study performed by the Epidemiology Unit of Tor
      Vergata University in Rome (Italy) to verify whether a national project regarding
      the elderly population (Progetto Obiettivo Anziani), has been put into effect
      across Italy and, in particular, whether, in the context of this project,
      Geriatric Evaluation Units have been activated. The study evaluated the
      structural features of the existing Geriatric Units, as well as the type of
      employed staff and tools used. The results confirm that multidimensional
      assessment of the elderly is well established in Italy even though Geriatric
      Evaluation Units across the country are very diverse with respect to the type of
      employed staff and their work experience. The number of elderly persons evaluated
      in the Geriatric Units appears to be low but this is also due to the fact that
      multidimensional evaluation is only one of the many activities performed by the
      Units. This fact should be reflected upon however, and may call for a greater
      investment in this important sector of geriatric care.

PMID- 17206170
TI  - [General practitioner and family practitioner are not synonyms: what is the
      difference?].

PMID- 17206180
TI  - [Risk assessment and risk management].

PMID- 17206181
TI  - [Design and implementation of evidence-based measures for the prevention and
      treatment of tobacco use disorder: the experience of the Public Health Department
      of the Cesena Local Health Authority].
AB  - Tobacco smoke is the main cause of preventable death in Italy. It is important
      therefore to develop evidence-based measures aimed at preventing and treating
      tobacco addiction. This article describes the "Smoke-free" community project,
      implemented in the territory of the Cesena Local Health Authority. The success of
      the project shows that it is possible to carry out inter-sectorial and evidence
      based prevention. It also leads to considerations about the role of Prevention
      Services in the fight against tobacco smoke.

PMID- 17206182
TI  - [Epidemiology of falls among the elderly].
AB  - INTRODUCTION: Falls among the elderly have important physical and psychological
      consequences. Interventions of proven effectiveness exist at individual and
      population level for their prevention. Studies conducted in other countries have
      estimated the prevalence and identified the health and environmental risk factors
      associated with falls, while in Italy, the information available is limited to
      elderly living in protected residences. To estimate therefore the prevalence of
      falls and to estimate the association between these events and different risk
      factors, a series of questions on falls and their possible determinants were
      included in Studio Argento, a cross-sectional survey of the state of health of
      the non-institutionalized population > or = 65 years of age that was conducted in
      2002 in 11 Italian Regions. METHODS: In each region, two-stage cluster sampling
      was used to sample 210 individuals. In the first phase, 30 communes were
      selected, with the probability of selection proportionate to their population; in
      the second phase, simple random sampling using the communal population register
      to select the persons to be interviewed. Interviews were conducted in the homes
      of the study subjects using a standardized questionnaire. Data from the 11
      regions were merged for purposes of the analysis, and the C-sample routine of Epi
      Info version 2002 was used to conduct the analysis, taking into account of the
      survey design and the size of the total population > or = 65 years in the various
      Regions. SUDAAN, an application of SAS was used for the calculation of the rate
      ratios (R.R.) and 95% confidence intervals (95% CI) and the population
      attributable fractions, taking into account potentially confounding variables.
      RESULTS: A total of 2,273 persons were included in the study. During the previous
      12 months, 651 (28.6%; 95% CI = 26.4%-30.7%) had fallen; of these 43.1% (95% IC =
      38.6%-47.7%) had fallen 2 or more times. Sixty percent (95% CI = 55,6%-64,2%) of
      those who had fallen reported having fallen at home. Risk factors for falls
      included stroke (adjusted RR = 1.4 (95% CI = 1.03-1.8)). diabetes (adjusted RR =
      1.7 (95% CI = 1.2-2.1)). visual difficulties (adjusted RR = 1.3 (95% CI = 1.02
      1.6)). urinary incontinence (adjusted RR = 1.3 (95%CI= 1.1-1.5) and physical
      inactivity (adjusted RR = 1.3 (95% CI = 1.03-1.5)). In addition, the consumption
      of anti-anxiety drugs was also associated with a greater risk of falls. The
      highest population-attributable fractions were seen for urinary incontinence
      (9.4%) and lack of physical activity (10.0%). CONCLUSIONS: Falls are common in
      Italian elderly and are linked with the fragility of aging. To prevent falls, it
      is necessary to intervene on factors associated with fragility. Methods include
      encouraging regular physical activity to improve equilibrium and muscle strength
      and the continuous monitoring of health status to prevent further deterioration.
      Moreover studies carried out in other countries have demonstrated that the
      multidisciplinary interventions targeted at persons who have already experienced
      a fall reduces their risk of further falls. These interventions consist of
      evaluations of visual acuity, balance, and gait and a review of clinical history
      with eventual modifications of drug therapy and the environmental risks in the
      home.

PMID- 17206183
TI  - [Political expertice of Public Health Scholars].

PMID- 17206184
TI  - [Evaluation of a questionnaire for measuring individual environmental exposure to
      disinfection byproducts found in drinking water].
AB  - Epidemiological studies to evaluate the association between environmental
      exposure to risk factors and negative health effects often use population level
      aggregated data to measure exposure, but do not consider personal characteristics
      that may affect the degree of exposure at the individual level. The aim of this
      study was to evaluate the validity and reproducibility of a questionnaire
      specifically designed to measure individual oral, inhalation and transdermal
      exposure to disinfection byproducts in drinking water. Reproducibility of the
      questionnaire was evaluated by administering the questionnaire twice, in
      different time periods, to the same subjects. On the other hand, validity was
      tested by comparing responses to the questions with information contained in
      diaries filled out by the subjects daily over a period of one week (gold
      standard). Questionnaire reproducibilty and validity were both found to be very
      good, as shown by high Spearman's correlaton coefficients, Intraclass correlation
      coefficients (ICC), kappa concordance coefficient, sensibility and specificity.
      The use of a questionnaire such as the one evaluated in this study may be a
      valuable aid when conductin epidemiological studies to assess individual
      environmental exposure to risk factors found in drinking water and to explain the
      effect of such factors on human health.

PMID- 17206185
TI  - [Reasons for turning to healthcare services outside of own area of residence: a
      study among patients of the AV1 Local Health Unit in Italy].
AB  - In this study, 552 patients from the AV-1 Local Health Unit, who accessed
      healthcare services outside of their own area or region of residence ("intra- and
      extra-regional mobility") were interviewed by their general practitioner. The aim
      was to describe the healthcare "mobility" phenomenon and the reasons patient
      resort to it. Most cases involve patients who turn to healthcare services outside
      their local area but within their own region of residence (intraregional
      mobility). On the other hand cases that involved "extraregional mobility", that
      is involved patients who accessed healthcare services outside their own region of
      residence , occurred in Basilicata, Puglia, Emilia Romagna and Lombardia. Reasons
      given by patients for this choice are, in order of importance: prestige of a
      specific hospital or hospital department, trusted physician working in a given
      hospital, disease severity, specialist advice, reduced waiting times, friends' or
      relatives' suggestions, better hospital services, lack of trust in healthcare
      services provided locally, advice given by general practitioner.

PMID- 17206186
TI  - [The mild cognitive impairment in the dementia: importance for Public Health].

PMID- 17206187
TI  - [Use of the Mini-Cog test as a screening method for dementia in the Italian
      population: the Argento Study results].
AB  - INTRODUCTION: This article describes the use of the Mini Cog test in a sample of
      elderly subjects participating in a multicentre Italian study on the healthcare
      needs of older adults. The Mini Cog is a simple screening test for cognitive
      impairment. It combines a brief memory test and a simply scored clock-drawing
      test and allows rapid screening for short term memory defects, learning and
      different cognitive abilities that are impaired in dementia patients. Various
      studies have shown that the Mini-Cog, which can be administered in as little as 3
      minutes, is as effective in detecting dementia as longer screening tests. In
      addition, it can be easily administered by personnel that is unfamiliar with
      cognitive testing. METHODS: The Mini-Cog test was administered to 2,186 elderly
      subjects participating in the Argento study, a study conducted in 11 Italian
      regions. Clocks were rated as abnormal (0 points) or normal (1 point) and 1 point
      was given for each recalled word in the memory test. A total score of 0-2 was
      considered positive for dementia. Two training courses were organized for the 11
      regional coordinators who were responsible for rating the clock drawing test. In
      order to validate the study results, 300 clocks were rated by expert raters who
      had developed the test. RESULTS: The test was acceptable to study subjects and
      less than 1% refused to perform the clock drawing test. Ratings by expert and
      local raters were found to be 90% concordant. The estimated prevalence of persons
      with a score >or=2 was 23.1% and double in persons over 75 years of age (65-74:
      16,4%; >or=75: 31,2%). No gender differences were observed. On the other hand
      large differences were observed between persons with different educational
      levels; in fact while 63.1% of illiterate subjects scored positive for dementia,
      only 8.9% of university educated persons had positive tests. CONCLUSIONS: The
      Mini-Cog test was found to be easy to administer by Italian Local Health Unit
      personnel in the context of evaluating healthcare needs of older persons. Study
      results were consistent with other population studies that evaluated cognitive
      impairment in elderly subjects in developed countries. In view of its high
      acceptability and reliability the Mini-Cog can be a valid screening tool for use
      in outpatient services and by general practitioners and in the planning and
      management of healthcare services.

PMID- 17206188
TI  - [Contamination by disinfection byproducts (DPBs) and microbiological quality of
      dialysis water: a study in an Italian hospital dialysis service].
AB  - Maintaining a high standard of quality of dialysis fluid has been shown to be
      difficult. For this reason, an evaluation of the microbiological quality (total
      bacterial count at 22 degrees C and 37 degrees C, pyrogenic Pseudomonas,
      Staphylococcus, Acinetobacter and Enterobacteriaceae) and contamination by
      disinfection byproducts, of dialysis fluids was carried out in a hospital
      dialysis service in Arezzo (Italy). The analysis was carried out in different
      points of the water treatment system used for the preparation of dialysis fluids.
      Results show diffuse microbiological contamination especially at the point of
      entry of the dialyzer monitor; Staphylococcus and Pseudomonas were found to be
      the most frequent contaminants due to the presence of biofilms in the water
      system, while pyrogenic bacteria were found to be within regulatory limits.
      Trichloroethane and trichloroethylene were absent but traces of carbon
      tetrachloride, percloroethylene and bromoform were found; these were outnumbered
      by trialomethanes (chloroform at point of entry decalcifier: mean 90.14
      microg/L). Contamination by trialomethanes decreased at the end of the
      distribution system (mean chloroform 8.55 microg/L). The yearly level of exposure
      of a dialysis patient to low molecular weight volatile halogenated organics
      (VHOs) that are able to pass the dialyser membrane, was therefore estimated to be
      approximately 100 mg.

PMID- 17206189
TI  - [BCG vaccination and development of an innovative vaccine for preventing vertical
      HIV transmission in Africa].
AB  - "Families First Africa" is an international project whose main objective is to
      develop a pediatric vaccine that protects infants against HIV transmission during
      breast feeding. The vaccine being developed consists of HIV peptides matching HLA
      genotypes of the Western Africa population and will be administered in
      association with BCG vaccine which acts as a strong adjuvant. An alternative
      strategy is to administer a recombinant BCG vaccine with HIV gene fragments which
      codify for the same peptides.

PMID- 17206190
TI  - [A possible scenario of pandemic influenza in Italy].
AB  - An influenza pandemic is expected to occur and will require timely
      countermeasures. Based on analysis of past influenza epidemics, a deterministic
      model was developed to estimate the expected number of cases (over 12 million),
      medical consultations (over 5 million), hospital admissions (over 220,000) and
      deaths (over 43,000) in the absence of public health interventions. The adoption
      of available measures would reduce the number of cases by about 22%,
      hospitalizations by 20%, and deaths by 28%.

PMID- 17206191
TI  - [Hospitalisation associated with Rotavirus gastroenteritis in Italy, 2001-2003,
      evaluated by means of ICD9-CM diagnostic codes].
AB  - Rotaviruses (RV) are the most common etiological agents in acute gastroenteritis
      (GE) in children in the first years of life. Data from the national scientific
      literature show that RV is responsible of 26% of all cases of hospitalisation for
      diarrea in children, resulting the most frequently identified agent. The Italian
      database of hospital discharge, freely available from the web site of the
      national Ministry of Health, was searched to investigate the epidemiology of RV
      gastroenteritis. The mean number of hospitalisation for RV enteritis in children
      in the first 4 years of live was 4.758 in the years 2001, 2002 and 2003,
      representing 84% of viral enteritis. RV was identified as agent in 17% of all
      intestinal infectious diseases in this age group. This percentage shows the
      important role of RV in severe gastrointestinal infections; it is however much
      lower than the value expected from specifically performed surveys. This
      underestimation may be attributed to the high number of undefined gastroenteritis
      found in the database (54%), to the scarce sensitivity of the hospital discharge
      code, and to the fact that the analysis was performed using only the principal
      diagnosis. A specific immunisation strategy, safe, effective, cost-effective and
      easy to perform, could have a great impact on the incidence of the disease and on
      the associated costs.

PMID- 17206192
TI  - [Hospitalisations for cataract surgery in Puglia 2000-2002].
AB  - Cataracts are a common condition and represent a frequent cause of visual
      disability. Nevertheless, data regarding the incidence of cataracts and the
      progression of and loss of vision due to cataracts is scarce. In this study,
      hospital discharge abstract data was evaluated to estimate the frequency and type
      of hospitalisations for cataract surgery that occurred in the Puglia region in
      the years 2000-2002. The results of this study confirm that cataract surgery
      accounts for a relevant amount of regional healthcare system costs. In fact,
      every year, over 25,000 lens surgery procedures, most of which age-related, are
      performed in the Puglia region. Approximately 90% of such procedures involve
      cataract surgery; age-specific hospitalisation rates show very high rates in the
      > 50 year old population. Only 25% of total cataract extractions were performed
      as a day-surgery procedure and the mean length of hospital stay was found to be
      2.5 days. This confirms that inappropriate hospitalisations, with respect to both
      type and duration, do occur. Cataract surgery is performed in over 30 hospitals
      in Puglia; the availability of health facilities in the region, therefore, seems
      to be satisfactory. In fact, on average, in the three-year period, only 7.5% of
      cases underwent the procedure outside the Puglia region.

PMID- 17206193
TI  - [A survey of preventive measures against infection risk in dental surgery].
AB  - In dental healthcare surgeries, both workers and patients are regularly exposed
      to various infectious agents. It is essential therefore that dental healthcare
      workers have a good knowledge of disinfection systems and that dentists'
      surgeries be effectively managed so as to reduce or even eliminate the risk of
      cross infections. In order to evaluate infectious risk prevention methods and
      describe the procedures used by dental healthcare workers on a daily basis, a
      sample of dentists who work in public surgeries were asked to anonymously fill up
      a questionnaire. The results of this survey show that dental healthcare workers
      are sufficiently well-informed about the infectious hazards present in the
      workplace and are aware of the high risk of exposure to infections but seem to be
      especially concerned about blood-borne infections (hepatitis, AIDS). Only 67.5%,
      however, are immunised against HBV. Individual safety devices are used correctly
      while there seems to be a lack of knowledge about the proper use of disinfection
      and sterilization systems. In addition, some dental healthcare workers still
      today refuse to treat HIV-positive patients.

PMID- 17206194
TI  - [Sanitary control of cosmetics].
AB  - In the Lombardia region (Italy), the function of sanitary control of cosmetic
      products has been delegated to the local health units (ASL). The Province of
      Milano 1 Local Health Unit therefore carried out a cosmetics surveillance
      programme involving 92 cosmetic firms located in its territory. Manufacturing and
      storage conditions of cosmetics produced by the local firms were evaluated and
      overall, good sanitary conditions were found.

PMID- 17206195
TI  - [Sanitary and nutritional control of the Catania school catering service].
AB  - Sanitary and nutritional control of meals distributed by school catering services
      is one of the institutional duties of the Food Hygiene and Nutrition Services
      (Servizi Igiene Alimenti e Nutrizione - SIAN) of the Local Health Units. In order
      to carry out this activity properly it is necessary to ask oneself beforehand
      what the main outcome of control activities should be. The answer to this
      question can only be that "proper nutrition is essential for healthy growth".
      Starting from this assumption, control activities performed along the entire
      chain of the scholastic catering service, starting from the final dish served at
      school up to the primary producer, were reviewed. The review was carried out by a
      team of multiprofessionals which included a physician, a prevention technician, a
      dietician, a biologist, an agronomist and a veterinarian. Preliminary results are
      extremely positive and show that the multidisciplinary integration of roles
      entrusted to the coordinators of SIAN is crucial to obtaining the best results.

PMID- 17206196
TI  - [Strategies for protecting the elderly from the health-risks of heat-waves:
      measures undertaken in Italy in the summer of 2004].
AB  - Heat waves constitute an important public health problem because of their
      potential serious health impact on vulnerable populations such as the elderly and
      individuals living in poor health, socioeconomic, cultural or environmental
      conditions. The summer of 2003 was the hottest summer, with respect to both
      minimum and maximum temperatures, of the last fifty years. During that summer, an
      increased mortality was found especially in the elderly population = 75 years.
      The Ministry of Health therefore released guidelines for the regions and other
      local authorities, regarding the measures be undertaken in order to safeguard the
      elderly and other vulnerable populations from the health risks associated with
      heat waves. Subsequently, a survey was performed to collect information regarding
      the projects put into practice in the summer of 2004 by the various regions and
      local authorities. The aim of the study was to promote a comparison and sharing
      of appropriately documented experiences. This article classifies and describes
      the various interventions that were put into practice.

PMID- 17206197
TI  - [Health impact assessment: a modern and heavy commitment for Public Health
      workers].

PMID- 17206198
TI  - [Evaluation of the cytotoxicity of cigarette smoke condensate by using different
      solvents].
AB  - The use of short term in vitro tests is an important step in the evaluation of
      the mechanism of action of cigarette smoke condensate (CSC). This study evaluated
      the effects of both CSC and solvents on Swiss 3T3 murine fibroblast cells.
      Results show that after 24 hours of treatment, CSC exerts a dose-dependent
      cytotoxic activity, both in methanol and dimethyl sulfoxide (DMSO), through
      mechanisms involving cell death and alterations in cell proliferation and
      metabolism. On the contrary, after 1 hour of treatment, a cytotoxic effect is
      seen only with CSC in DMSO. In cell cultures devoid of CSC, similar results have
      been obtained after 24 hours with both types of treatment.

PMID- 17206199
TI  - [Evaluation of hydrocarbon-oxidizing bacteria in port water and of health risks
      related to harbour activities: port of Otranto (Italy)].
AB  - The aim of this study was to evaluate the water quality of the port of Otranto
      (Italy), through a combined approach which integrates monitoring of traditional
      microbiological parameters and studying the dynamics of some autochthonous
      bacterial communities. The fecal contamination indicators, total coliforms, fecal
      coliforms, and fecal streptococci were measured to evaluate the sanitary aspects,
      while the presence of organic matter was considered as a parameter strictly
      related to dumping. In addition, being the port of Otranto especially exposed to
      hydrocarbon pollution, hydrocarbon-oxidizing bacteria were evaluated. Fecal
      contamination indicators were consistently found to be below the threshold values
      set by the Italian legislative decree N. 470/82 for bathing waters, indicating a
      good microbiological quality of these waters. A higher density of hydrocarbon
      oxidizing bacteria was found at mooring and craft transit areas. This parameter
      was therefore found to be useful for evaluating port water hydrocarbon pollution.

PMID- 17206200
TI  - [Socio-demographic determinants of physical activity in Italy].
AB  - A cross-sectional study was performed to evaluate the determinants of physical
      activity in Italy, by analysing data from the Italian Institute of Statistics
      (ISTAT) study regarding the health status and use of health services of the
      Italian population in the years 1999-2000. Multiple logistic regression analysis
      of data highlighted a lower propensity of women, smokers, ex-smokers, and
      individuals with a lower educational level, to engage in physical activity. These
      data are useful for planning targeted prevention strategies.

PMID- 17206201
TI  - [Utilization of the results or research about nursing workload in a surgical
      suite, based on the methodology of the "Projet de Recherche en Nursing" (PRN87)].
AB  - The aim of this study was to evaluate actual levels of nursing care delivered in
      a functionally aggregated Surgery Area of the Tor Vergata University Hospital in
      Rome, by measuring nursing workload according to the "Projet de Recherche en
      Nursing" (PRN87) methodology. The study was performed between February 1st and
      June 26, 2004. The results of the study have highlighted the fact that nursing
      staff is often improperly used, for example to perform many administrative
      activities, thereby reducing the quality and amount of direct nursing care.

PMID- 17206202
TI  - [Particulate matter (PM10) air pollution, daily mortality, and hospital
      admissions: recent findings].
AB  - The first studies conducted to evaluate a possible association between air
      pollution and mortality date back to the serious events that occurred in the Mosa
      Valley, Belgium (1930), in the small city of Donora ("killer fog" incident of
      1948) and in London (1952). The latter episode led to the introduction of air
      pollution control policies. Following the introduction of air pollution control
      measures in economically advanced cities in the 60s and 70s, the concentration
      levels of pollutants reached were believed, for many years, to be risk free.
      However, despite improvements in air quality achieved by many industrialized
      countries the negative effects of air pollution remain today an important public
      health problem. Among all air pollutants, particulate matter is the type of air
      pollution that causes the most numerous and serious effects on human health,
      because of the broad range of diverse toxic substances it contains,. For this
      reason, when assessing human health risk, PM10 may be considered to be a reliable
      indicator of the impact of global air pollution. Various epidemiologic studies
      conducted in the last 10 years, such as the Air Pollution and Health-European
      Approach (APHEA) project, the National Morbidity, Mortality and Air Pollution
      (NMMAPS) Study and Italian Meta-analysis of Studies on the short-term effects of
      Air pollution (MISA), have shown that current ambient concentrations of PM10 may
      lead to increased mortality and morbidity. Various studies have reported mean
      increases in mortality below 1% for 10 ?g/mc increases of ambient PM10. Studies
      have also underscored the role of particulate matter in aggravating
      cardiorespiratory diseases and consequently increasing hospital admissions. Air
      quality standards have been recently revised by legislation. The EU has issued a
      directive that sets limiting values and, where appropriate, threshold values, for
      the different air pollutants.

PMID- 17206203
TI  - [Travel-associated Legionellosis: emerging illness or epidemiological reality?].
AB  - Travel for business or tourism has become increasingly common in the age we live
      in. The great volume of national and international traffic and the speed of
      transportation are inevitably linked to a possible increased risk of acquiring
      certain illnesses such as Legionellosis, which, in fact, has shown a consistently
      increased incidence in recent years. In this paper, a brief introduction
      regarding the etiology and clinical and epidemiological characteristics of the
      disease, is followed by recent national and international data regarding its
      diffusion and guidelines for its prevention and control.

PMID- 17206204
TI  - [Guidelines for preparing informative material for obtaining informed consent
      from individuals undergoing diagnostic and therapeutic procedures].
AB  - The authors describe the ethical principles and legal basis of obtaining informed
      consent for diagnostic and therapeutic procedures. They also quote a text of
      proposed guidelines directed at rationalizing activities, behaviours and
      modalities of obtaining informed consent in a hospital setting. In line with the
      general objectives of guidelines, such as improvement of results through
      behaviour changes, including reduction of the variability of behaviour, a
      standard form is proposed for obtaining a valid informed consent.

PMID- 17206205
TI  - [Plans and vaccination calendar in the Italian regions].

PMID- 17206207
TI  - [Population's health and individual health].

PMID- 17206208
TI  - [Short-term hospitalization: experience in Otorhinolaryngology and Orthopedics].
AB  - The activation of short-term hospitalization in the Otorhinolaryngology and
      Orthopedics departments of a medium-sized hospital has led to considerable
      rationalization of costs, as well as to organization of patient care based on
      level and intensity of treatment required, less social and psychological
      discomforts for patients, and to a higher level of integration between hospital
      and community services. This experience, of 10 months duration, may be taken as a
      model of a concrete organizational and functional transformation and of
      adaptation to the demand and supply of healthcare services.

PMID- 17206209
TI  - [Psychiatric residential care facilities in the Puglia region. Phase 1 results of
      the PROGRES project].
AB  - One of the more important aspects of the psychiatric care reform in Italy has
      been the opening of a great number of psychiatric Non-Hospital Residential
      Facilities (NHRF). However, 22 years have elapsed since the reform and there are
      still very scarce data regarding such facilities, the type of patients being
      accomodated, and the types of treatments provided. The "PROGRES" (PROGetto
      RESidenze - Residential Project) project is the first national study regarding
      NHRFs ever carried out in Italy. The objectives of "PROGRES" are to make a survey
      of all NHRFs in Italy (Phase 1) and to perform a detailed assessment of 20% of
      the surveyed facilities and of the type of patients being treated (Phase 2). This
      paper reports the survey (Phase 1) results for the Puglia Region. As of March 31,
      2003, 113 psychiatric residential facilities were present in Puglia, with a total
      of 1.479 beds. This results in an average of 13,08 beds per facility and a rate
      of 3,86 beds per 10.000 inhabitants. The number of NHRFs present in the territory
      of each Local Health Unit in Puglia is very variable. Most NHRFs (57%) opened
      after January 1997. Eighty-three percent have a 24-hour staff coverage while only
      5,3% has a 2-hour staff coverage. Eighty five percent of the residential
      facilities are financed by the Italian National Healthcare System, while a small
      percentage is privately funded. In over half (69,93%) of the NHRFs the
      predominant patient age group is 40-59 years; 26,4% of the residential facilities
      accommodate patients below age 40 and only 3,53% accommodate patients over 60
      years old.

PMID- 17206210
TI  - [ALEE-AO: epidemiologic and economic atlas of hospital activities in Lombardy].
AB  - This paper describes the main characteristics of a data processing system that is
      available through the Internet and that is used to process epidemiological and
      economic data, predominantly from a geographical viewpoint, starting from the
      hospital discharge abstracts of the Lombardy Region. Technical aspects of the
      system are briefly reviewed, including epidemiological-statistical aspects
      (incidence, prevalence, variety of diagnoses, indicators, controlling for
      statistical variability, etc.) and aspects relating to information systems
      (hardware platform, software environment, Internet access and security problems,
      original database, etc). The system introduces several methodological innovations
      in the processing of hospital discharge abstracts (such as links between data
      files, evaluation of activity of each individual GP, and analysis of patient
      mobility), proposes three successive levels of case selection (time, geography,
      nosology) prior to statistical analysis which is performed starting from the
      information on each individual discharge abstract. Finally, several examples are
      given and critical aspects, as well as prospects of the system, are discussed.

PMID- 17206211
TI  - [Comparing two different techniques to assess the appropriateness of admissions
      provided in the emergency room of a pediatric hospital].
AB  - Two different techniques aimed to assess the appropriateness of hospital
      utilisation were used to study the same sample of clinical records of admissions
      provided during 2001 by the emergency room of a pediatric sicilian hospital. The
      first technique estimated the '"high risk of inappropriateness" DRGs prevalence,
      according to the Decreto del Presidente del Consiglio dei Ministri of 29 Novembre
      2001, and the second was the pediatric version of the Appropriateness Evaluation
      Protocol (AEP), based on clinical characteristics of patients and complexity of
      assistance provided. The comparison of results did not show any agreement between
      the two techniques (kappa= 0,031, C. I. 95%: from -0,001 to +0,062). In a
      paediatric emergency room AEP criteria cannot be used as clinical guidelines
      aimed to reduce the prevalence of "high risk of inappropriateness" DRGs.

PMID- 17206212
TI  - [An intervention model for smoking prevention strategies].
AB  - Tobacco smoke represents the main cause of preventable morbidity and mortality in
      Western countries: in Italy, approximately 85.000 persons die each year because
      of smoke-related illnesses. Starting from the objectives defined by the 2001/2003
      National Healthcare Plan, the Department of Prevention of the "Roma B" Local
      Health Unit elaborated a three-year project for the fight against tobacco smoke.
      The general objectives of the project are: to prevent young people from starting
      to smoke, to promote stop-smoking initiatives (with the involvement of General
      Practitioners) and to protect non-smokers from passive smoking (in the context of
      a smoke-free health facilities program). A special technical-scientific committee
      was set up to evaluate the effectiveness of the smoking prevention interventions.

PMID- 17206213
TI  - [Sexually transmitted diseases: a public health issue].
AB  - Sexually Transmitted Diseases (STDs) are a main problem in the public health
      policy. The importance of these diseases is not only limited to their high
      incidence but also to the complications they may cause and to their role in the
      HIV transmission. Control of STDs represents one of the main aims of the World
      Health Organization. For many years STDs were thought to have been almost
      completely eliminated; instead, recently the rates of STDs are increasing. This
      has prompted the search for control strategies, that, however, have shown to be
      difficult to implement. For this reason, prevention programs based on promotion
      of responsible sexual behaviour, early diagnosis and treatment, and reduction of
      infectiousness, have been implemented in many countries.

PMID- 17206214
TI  - [New progress in public health].

PMID- 17206215
TI  - [Further research on the kinetics of inactivation of HAV and enteroviruses with
      peracetic acid. Note II].
AB  - Further research was performed on the disinfectant efficacy of peracetic acid on
      viruses. Hepatitis A virus (HM-175 strain), Poliovirus 2 (attenuated strain) and
      Coxsackie virus B5 (isolated strain) were tested using peracetic acid
      concentrations between 160 mg/l and 1280 mg/l. Inactivation tests were carried
      out at +20 degrees C and at 3 different pH conditions, acid, neutral and basic.
      The results confirmed that HAV virus, which showed a decline with concentrations
      above 320 mg/l, has the highest resistance with respect to the other viruses. The
      other two Enteroviruses were found to be less resistant, especially in neutral
      and acid conditions.

PMID- 17206216
TI  - [Evaluation of occupational safety training effectiveness in healthcare workers].
AB  - OBJECTIVES: In Italy, Legislative Decree N.626/94 introduced new occupational
      safety rules and prevention measures to decrease or eliminate risk factors in
      workplaces. These issues are important even in the hospital setting where
      healthcare workers, especially nurses, are exposed to various hazardous
      substances and do not always follow the appropriate workplace safety practices.
      According to LD 626, safety training should be used to communicate and educate
      workers about occupational safety and health issues and modify at-risk behaviors.
      However, training effectiveness should be evaluated. The aim of this project was
      to evaluate the effectiveness, in terms of acquired knowledge, of a
      chemical/biological risk training course aimed at nurses and nursing students.
      METHODS: Three groups of nurses and nursing students participated in the training
      course. Knowledge acquired by the participants was evaluated by means of pre- and
      post-tests. Post-tests were given immediately after the course and three months
      later. RESULTS: The proposed evaluation method allowed us to identify and explain
      relevant occupational safety and health issues regarding chemical risk. Data
      analysis showed that the multimedial teaching method used was effective; in fact,
      the teaching method generated debate within the audience, and led to diffusion
      and consolidation of knowledge.

PMID- 17206217
TI  - [Testing for Pseudomonas aeruginosa: an additional parameter for assessing
      microbiological quality of dialysis water].
AB  - In 1995 the regional council of the Lazio region passed Decree N.1650 which
      regulates the maintenance of dialysis equipment and sets limiting values for
      microbiological and chemical parameters used to assess the quality of water used
      for dialysis fluids. As regards the microbiological parameters, limiting values
      were set for total bacterial count and endotoxins. However, in recent literature,
      serious health effects following dialysis have been described; these suggest the
      advisability of including testing for more specific microorganisms and of testing
      greater samples of dialysis water. In this study, conducted over 2 years, in
      addition to normal microbiological parameters, dialysis fluids were tested for
      the presence of bacteria of the Pseudomonas species. Results show that samples
      which met the standards for dialysis water set by legislation were actually found
      to be contaminated by Pseudomonas species.

PMID- 17206218
TI  - [Genetically modified organisms: European and Italian legislation to protect
      citizens' health].
AB  - The development of GM foods and organisms has concentrated everyone's attention
      on the importance of food safety and on protecting citizens' health, and
      inevitably influenced healthcare policies regarding food safety. Personal ethical
      beliefs regarding food and in particular, the consumption of foods derived from
      biotechnology should be taken into account when deciding healthcare policy. AIM:
      The aim of this study was to analyse whether European, Italian and Regional
      legislation meets basic human rights regarding health and the right to choose,
      based on the precautionary principle. METHODS: European and Italian laws
      regarding the production and marketing of GM foods were analysed and compared to
      food safety legislation, in order to evaluate how and to what degree existing
      legislation protects consumers' right to choose. Results show that existing
      legislation protects consumers from possible foodborne diseases, but the right to
      informed consent and to free choice is not warranted. Existing laws do not attach
      enough importance to consumers' right to information; arbitrary threshold levels
      set for labeling and clauses concerning technical causes allow food businesses to
      avoid labeling and do not give consumers the possibility of making an informed
      choice.

PMID- 17206219
TI  - [A call for organizational and managerial changes in primary and hospital care
      services].
AB  - The changing epidemiological situation and socio-economic conditions in Italy
      have led to a situation where the Italian health care system no longer adequately
      satisfies the actual needs of society. Organizational and managerial changes in
      both primary and hospital care are needed and are proposed in this article. As
      regards general practice and primary healthcare it is crucial that a stable and
      exclusive relationship between GPs and their patients be regained through
      continuous and qualified care by the GP. This can be achieved through the
      establishment of primary care structures where a team of general practitioners
      work in association with nursing personnel for the delivery of key services
      including continuous at-home assistance. As for the organization of hospital care
      it would be useful to set up, in addition to existing general hospitals, "zonal
      inpatient facilities", resembling the old "infirmaries", directed by a
      specialized nurse and with a small full-time medical staff. In these facilities,
      designed for brief hospitalizations of patients with chronic conditions, GPs
      could take part in the management of their patients. Two important results could
      be achieved by establishing such facilities: a substantial reduction of
      healthcare costs related to frequent hospitalizations of patients with chronic
      medical conditions, and a structural reorganization of existing hospitals.
      Presently hospitals are often too large especially considering the continuous
      progresses made in diagnostic and therapeutic techniques which allow consistently
      shorter lengths of hospital stay and consequently, a more rapid turnover of
      patients.

PMID- 17206220
TI  - [Disability management: a new approach to prevention].
AB  - Disability Management (DM) is a workplace prevention and care strategy aimed at
      having healthier and more productive workers and improving company
      competitiveness. The DM process consists of 4 phases: wellbeing promotion,
      preventive measures, early intervention and case management. To be successful, DM
      requires a team approach which co-involves DM experts, employees, supervisors,
      human resource management staff, union representatives, physicians and other
      health operators.

PMID- 17206221
TI  - ["The hedgehog and the fox" of public health].

PMID- 17206222
TI  - [Trends in mortality due to the main causes of death in Umbria (Italy), 1994
      2004].
AB  - In order to obtain information regarding the efficacy of healthcare services in
      the region of Umbria (Italy), trends in mortality due to the main causes of death
      in this region, between 1994-2004, were analysed. Mortality data was collected
      from the Nominal Registry of Causes of Death. Standardized mortality and years of
      potential life lost (YPLL) rates, and cumulative death risk were used as
      indicators. Joinpoint regression was used to determine whether temporal changes
      in indicator trends were statistically significant. The joinpoint analysis of
      mortality trends has shown that general mortality, as well as specific mortality
      due to malignant tumors, cardiovascular disease, gastrointestinal disease and
      accidental causes declined over the examined time period. Statistically
      significant decreases in the indicators used were constant over time: in fact,
      joinpoints were found only for YPLL and cumulative risk trends for cardiovascular
      disease-related mortality. These results have provided important information
      regarding healthcare in the Umbria region.

PMID- 17206223
TI  - [The management control system of the Roma/C Local Health Authority. Financial
      year 2004].
AB  - The aim of this study was to describe the budgeting process of the Roma/C Local
      Health Authority during the 2004 financial year. The planning-control process,
      which included preparing regular reports, allowed performing comparisons between
      actual with planned results so that the necessary corrective actions could be
      taken in a timely manner. It also led to a confrontation between the various
      managers involved, regarding: 1. the conversion of ordinary regime hospital beds
      into day hospital beds; 2. the development of a new model of emergency care aimed
      at integrating care between the hospital and the community; 3. the need to
      implement dataware housing.

PMID- 17206224
TI  - [Survey on vaccination strategies used in different Italian Regions, for the 7
      valent conjugate pneumococcal, meningococcal C and varicella vaccines].
AB  - A survey was performed to obtain information regarding regional vaccination
      strategies in Italy, for 7-valent conjugate pneumococcal, meningococcal C and
      varicella vaccines. A questionnaire was sent to the person in charge of
      infectious disease control and vaccination activities in each of the 21 regions.
      All 21 regions replied to the questionnaire. Twenty regions offer pneumococcal 7
      valent conjugate vaccine free only to high-risk children, while 9 of these
      regions offer it to all newborns as well. Seventeen regions offer meningococcal C
      vaccine only to high-risk individuals while 9 regions offer it to all newborns.
      All 19 regions that have deliberated on varicella vaccination offer it to high
      risk subjects only while 3 offer it also to all newborns. Local health
      authorities were found to widely adhere to regional deliberations regarding these
      vaccinations. Vaccination strategies for the three vaccines are not uniform
      across Italy. Additional efforts are required to ensure that high-risk subjects
      in all regions receive these vaccines and to homogenize immunization strategies
      aimed at other target groups. Monitoring of coverage levels and disease
      surveillance will allow evaluation of the impact of vaccination strategies
      implemented in the different regions.

PMID- 17206225
TI  - [Risk management project: reactive or proactive approach?].
AB  - Risk management in healthcare refers to the process of developing strategies
      aimed at preventing and controlling the risk of occurrence of errors and harmful
      events. The final objective is primarily that of increasing patient safety and
      secondarily, that of reducing the financial burden of adverse events. The
      implementation of a risk management system is therefore of vital strategic
      importance. Nevertheless, a fundamental question that needs to be answered in the
      operational phase is: should a proactive or reactive approach to risk management
      be taken? In our view, proactive risk management has many advantages over a
      reactive approach and is therefore preferable. The reactive approach should be
      taken exclusively to obtain information regarding risk and errors, in the
      preliminary, as well as monitoring and follow-up phases of the project.

PMID- 17206226
TI  - [Positive predictive value of ICD-9-CM codes in hospital inpatient discharge
      abstract records, for identifying adverse events].
AB  - A retrospective study was conducted in the ambit of Risk Management research, in
      order to assess adverse events in patients hospitalised in hospitals in one Local
      Health Authority of the Piemonte region. Specifically, the aims of the study were
      to: evaluate the relative frequency of ICD-9-CM codes used to define adverse
      events, with respect to the total number of hospital discharge records submitted
      in 2003; identify true and false positives, by hospital chart review; estimate
      the positive predictive value (VPP) of the ICD-9-CM codes used, and determine, in
      each case, whether the adverse event had led to hospitalisation or if it had
      occurred during hospitalisation. Results show that the ICD-9-CM codes used
      effectively identify adverse events. In fact, the probability that an ICD-9-CM
      code will accurately identify an adverse event is 100% for codes in the
      "Misadventures of surgical and medical care" category of adverse events, 62.8%
      for codes indicating "Complications of medications (adverse drug events)" and
      56.8% for the "Complications of surgical or medical procedures" category. In most
      cases the adverse event had occurred prior to hospital admission.

PMID- 17206227
TI  - [The importance of the motivation of human resources in health care
      organizations].

PMID- 17206228
TI  - [Treatment of thermal pool waters].
AB  - No laws currently exist regarding the treatment of spa pool water, since it is
      not completely logical that these should have the same requirements as normal
      swimming pools. The problem arises especially with regards to the use of chlorine
      as a disinfectant, which may actually annulate the therapeutic effects of spring
      waters by altering their physical-chemical characteristics. Possible choices may
      be represented by frequent replacement of pool water, which may be easily
      achievable for small pools but more difficult to implement for larger pools, or
      by alternative disinfection methods such as ozone or ultraviolet rays. The
      efficacy of these methods must be shown through frequent chemical and
      microbiological analyses and future, to be hoped-for laws or guidelines, will
      need to be aimed at defining safety performance standards rather than prescribing
      analytical intervention and control methods. Beyond the choice of disinfection
      method, it is extremely important to highlight some relevant hygienic measures
      that bathers should take and that play a fundamental role in preventing
      infectious diseases which may be acquired in pools. The most important of these
      include: showering before entering the pool, wearing slippers around the pool,
      not urinating in the pool, not bathing if affected by diarrhea, wearing a bathing
      cap, avoiding the use of contact lenses while bathing and avoiding exchanging
      towels. Pool managers have the important role of avoiding overcrowding of the
      facilities and ensuring that all technological systems function properly.

PMID- 17206229
TI  - [Vaccination and vaccines on the Internet: contrary and critical positions].
AB  - Using Google, sites expressing position against, or critical towards,
      vaccinations have been searched among the first 200 pages obtained using both
      "vaccine" and "vaccination" as key words. Position against compulsory vaccination
      or doubt about vaccine safety were found in 47 pages. The repetition of false
      news induces to think they are true and difficult to refute, while vaccine
      preventable diseases continue to cause damages.

PMID- 17206230
TI  - [The New Italian Health Information System].

PMID- 17206231
TI  - [Bioinformatics and GenEnv database in biological risk management].
AB  - Identification and molecular typing of environmental isolates by molecular
      techniques requires knowledge of the genetic characteristics of the microbe
      species being examined. The introduction of automated sequences has greatly
      speeded up the entire sequencing process as well as improved the accuracy of the
      collected information. Bioinformatics tools have become indispensable not only
      for setting up research studies, but also for storing, organizing and managing
      enormous quantities of sequencing data. Despite its great advantages, the use of
      bioinformatics is hindered by difficulties in learning how to use its software
      tools. The GenEnv database was developed to provide operators involved in
      biological risk management with a user-friendly tool for sequence analysis.
      Presently, there are over 20.000 sequence records, and over 9000 bacterial
      species represented in the database. The initial gene set comprises rDNA16S,
      rpoB, gyrB. The system allows sequence-driven microbe identification as well as
      the development of study protocols for research on specific microbe species.
      Nucleotide sequences are represented graphically. The GenEnv database was
      designed as a tool for public health operators but also offers wide prospects for
      scientific research.

PMID- 17206232
TI  - [The nurse's role in the management of patients with type 2, non-insulin-treated
      diabetes: the current state in Friuli Venezia Giulia].
AB  - Patient education is well known to be an essential aspect in the management of
      diabetes mellitus. This report aims to provide a general review of nursing care
      management for patients with diabetes mellitus, in particular non-insulin
      dependent type 2 diabetes, at either the inpatient or outpatient levels, in
      Friuli Venezia Giulia. Furthermore, it aims to identify the factors that may be
      preventing the implementation of adequate diabetes nursing care. We have
      identified 48 professional nurses formally involved in centres for diabetic care
      with a response rate of 87.5%.

PMID- 17206233
TI  - [Semi-permanent make up and tattooing equipment: safety and health issues].
AB  - The UK's Health and Safety Executive (HSE), at Machinery Directive Administrative
      Cooperation meeting, brought a problem to the attention of semi-permanent make up
      equipment sold in the European market, that may pose a health risk due to
      microbiological contamination. Considering that body adornment techniques are
      becoming increasingly popular, a study was carried out to evaluate the technical
      characteristics of such equipment and to collect information on the National and
      European regulatory situation. In most member states of the European Community,
      tattooing and semi-permanent make up activities are not regulated by specific
      laws. In Italy, the "Guidelines for safe tattooing and piercing practices" were
      laid down by the Ministry of Health in 1998 (Notes N. 2.8/156 of 5 February 1998
      and n.2.8/633 of 16 July 1998). This paper discusses the need to implement the
      above guidelines and to harmonize European legislation on the subject.

PMID- 17206234
TI  - [The Portfolio Activities Matrices; a strategic planning tool for guiding
      decision making in healthcare management].
AB  - Management of healthcare organizations relies on the availability of decision
      making tools. The Portfolio Activities Matrices is a method that can be applied
      to healthcare management. It allows simultaneous evaluation of indicators of
      efficiency, case-mix, cost and demand, so that the strengths and weaknesses of
      the organization may be identified. The method is complex and may have some
      degree of subjectivity. Nevertheless, it is a useful tool for performing the
      evaluations necessary for strategic planning management decisions, which must
      consider available resources as well as the social role of the organization.

PMID- 17206235
TI  - [Food labelling and the role of consumers. Note n. 1].
AB  - Food labelling regulations increasingly involve the use of tools and procedures
      that give consumers a more active role in the assessment of food safety and in
      the application of risk management processes. In Europe, compulsory food
      labelling has been introduced for all foods, whether pre-packaged or not. To
      better define the consumer's role in the food safety evaluation process, this
      first note discusses the inspiring principles of the European and the Italian
      legislation on this matter. In addition, guidelines are provided for adapting
      food safety procedures to modern risk evaluation strategies in an effort to
      minimize risks for the consumers.

PMID- 17206236
TI  - [Medical records and third party personal data processed in the patient's
      interest].
AB  - The authors examine some critical aspects relating to the management of sensitive
      personal data of individuals (third parties) other than the patients. The issue
      raised is that of how consent can be obtained for treatment of third party
      personal data when the subject is not available to give consent, and what should
      be done if consent is not given. In some cases it can be difficult to decide
      whose interests should prevail. The authors recommend using caution when
      processing third party personal data and to collect third party information only
      if strictly indispensable. They also discuss what should be done when a third
      party requests information regarding whether personal data, of which that
      individual is the data subject, is being processed by the health institution. The
      authors conclude that more time will be required before the full protection of
      personal information is achieved.

PMID- 17206237
TI  - ["Quality of life" of the elderly population: a survey to evaluate elderly
      people's self -perceived health in 11 Italian regions (Argento Study, 2002).].
AB  - Self-perception of health influences the quality of life of the elderly. In order
      to identify the more vulnerable elderly and guide interventions to improve health
      in this population group, we evaluated self-perceived health of elderly people
      through a set of 4 questions called the "Healthy Days Measures", which were
      incorporated into the Argento Study. The latter is a study performed to evaluate
      the health status of the elderly population in 11 Italian regions (2002).
      Methods. Following cluster sampling, 2,369 elderly subjects (>64 years) were
      interviewed at home, by trained personnel, through a standardized questionnaire.
      Self-rated health (on a scale from poor to excellent) was estimated, as well as
      the average number of days during the previous month when physical or mental
      health was not good and the number of activity limitation days. Multivariate
      analysis was performed using Sudaan software and by considering the following
      outcomes: self-perceived health, physical or mental problems or activity
      limitations for more than 1 day. Prevalence rates by gender, age, civil status,
      education level, home situation, place of residence, chronic diseases, dependence
      on a caregiver, sedentariness and social isolation, were calculated. Results.
      34.7% of interviewed subjects rated their health as good to excellent. A
      significantly lower proportion of women, older subjects (>75 years), those with a
      lower education level, those residing in southern Italy, those suffering from
      chronic illnesses, those dependent on a caregiver, and socially isolated or
      sedentary subjects rated their health favorably. The mean number of physically
      and mentally unhealthy days (summary index) was estimated to be 11.3 per month.
      Multivariate analysis showed that female gender was significantly associated with
      all outcomes considered; age and education level did not show any significant
      associations with the outcomes considered; depression was significantly
      associated with self-rated health and with number of mentally unhealthy days;
      physical dependence and sedentariness were associated with an increased risk for
      all outcomes, especially activity limitation days. Conclusions. These results
      suggest that depression, physical dependence and sedentariness influence self
      perceived health more so than socio-demographic characteristics. Public Health
      may have a relevant role in promoting and guiding interventions to prevent these
      factors in the elderly. The introduction of Healthy Days measures in health
      surveillance systems may be an important public health tool for monitoring
      perceived health status and in intervention planning and evaluation at both the
      national and local levels.

PMID- 17206238
TI  - [Attitudes and risk-taking behaviour for HIV infection, of drug addicts followed
      by a Drug Addiction Treatment Service (Ser.T).].
AB  - A questionnaire was administered to 160 injection drug users, enrolled in a
      methadone or buprenorphine maintenance treatment program at their local Drug
      Addiction Treatment Service (Ser.T), in order to measure their attitudes and risk
      taking behaviours towards HIV. Despite being on a maintenance treatment program,
      almost half of the interviewed subjects (43,75%) declared that they continued to
      use drugs, occasionally (15,62%), monthly (6,25%), weekly (10,62%) or daily
      (11,25%). Moreover, a high rate of risk-taking behaviour for HIV was found among
      the interviewed drug addicts, such as sharing of injection equipment (39,40%),
      irregular condom use (15,00%) and unprotected sex with casual partners (9,40%).
      When asked about which interventions they would consider to be most effective for
      HIV prevention, more than half of the interviewed subjects (58,12%) indicated
      qualified information regarding HIV transmission, while a lower but not
      negligible proportion of subjects thought the free distribution of syringes
      (21,25%) or condoms (20,63%) would be most effective. In contrast to other
      studies, our results show that pharmacological maintenance treatments may not
      have a role in preventing HIV infection among injection drug users. On the other
      hand, our results suggest that the presence, within the Ser.T team, of
      professional educators specialized in the prevention of sexually transmitted
      diseases may be more useful.

PMID- 17206239
TI  - [A new method for the detection of coliforms and Escherichia coli in water
      intended for human consumption.].
AB  - The ISO reference method, defined by the European Drinking Water Directive for
      the enumeration of total coliforms and Escherichia coli in water intended for
      human consumption, has various limitations, especially related to discrepancies
      observed with the new taxonomic classification of the coliform group. A study was
      therefore performed to compare the above reference method with another rapid
      method, the DST/Colilert, and to evaluate the phenotypical characteristics of
      isolated microrganisms. The ISO reference method failed to detect a significant
      proportion of coliforms and E. coli in water and furthermore, it enumerated
      microrganisms belonging to other groups. The DST/Colilert method was found
      instead to be a suitable alternative method for the detection of bacterial
      indicators.

PMID- 17206240
TI  - [Evaluation of viral and bacterial contamination of coastal seawater.].
AB  - The aim of this study was to determine whether testing for faecal contamination
      of water through evaluation of traditional bacteriological indicators, as per
      Directive EEC 76/160, effectively correlates with the presence of viruses in
      water. The study was performed both on water samples and bivalve molluscan
      shellfish (Mytilus galloprovincialis) with the further objective of evaluating
      whether mussels could be used as bioindicator organisms for assessing faecal
      pollution of water. Overall, 23 sea-water samples and the same number of mussels,
      taken from three sites along the Salento coast in southern Italy, were analysed
      to detect total and faecal coliforms, faecal streptococci, E. Coli, Salmonella
      and enteric viruses. The results of the study confirm that viruses and bacteria
      do not always follow the same trend. In fact, in one of the two water samples
      which tested positive for viruses, bacteriological indicators of faecal
      contamination were found to be below the limits established by current
      legislation and Salmonellae were absent. Similar results were obtained in the
      sample of mussels which tested positive for viruses. Conflicting results were
      obtained in the two examined matrices. This study highlights the importance of
      searching for viruses in the water environment and the possibility of using
      mussels as bioindicators for monitoring virological quality of coastal sea
      waters.

PMID- 17206241
TI  - [Survey of the Council of Residents of the Italian Society of Hygiene (SItI) on
      the smoking habits of physicians training in Hygiene and Preventive Medicine.].
AB  - This study was conducted on a sample of physicians training in Hygiene and
      Preventive medicine to evaluate their: smoking habits, awareness of the effects
      of cigarette smoke on health and attitudes regarding antismoking legislation.
      Data was obtained through administration of an anonymous questionnaire. A total
      of 220 physicians were interviewed: 27% was found to be a smoker while 45% of
      smokers stated that they did not want to quit smoking. These results are similar
      to those obtained for the general population. Amongst the residents of the
      various schools of specialisation, there are large differences in habits,
      awareness and attitudes towards smoke: a lack of professional training on the
      subject is present.

PMID- 17206242
TI  - [In Process Citation].

PMID- 17206243
TI  - [Employment opportunities and education needs of physicians with specialty
      training in Hygiene and Preventive Medicine.].
AB  - This survey was carried out under the sponsorship of the Italian Society of
      Hygiene (SItI), to evaluate the current professional position of physicians who
      completed their post-graduate professional training in Hygiene and Preventive
      Medicine in the years 2000 through 2003. An ad-hoc questionnaire was administered
      to 689 such specialists across Italy with a response rate of 40%. The results
      show that specialists in Hygiene and Preventive Medicine are generally satisfied
      with their professional choice though most specialists were found to have only
      temporary employment. Post-specialty training courses of major interest to
      specialists in Hygiene and Preventive medicine are those regarding occupational
      health, statistical analysis and epidemiology, and quality of health care.

PMID- 17206244
TI  - Development and numerical solution of a mechanistic model for corneal tissue
      ablation with the 193 nm argon fluoride excimer laser.
AB  - We detail the development and implementation of a global ablation model that
      incorporates a dynamically changing tissue absorption coefficient. Detailed
      spectroscopic measurements rule out plasma-shielding effects during the laser
      tissue interaction and thereby support a photochemical mechanism. The model
      predicts ablation rate behavior that agrees well with a variety of experimental
      ablation rate data and that substantially deviates from a static Beer-Lambert
      model. The dynamic model predicts an enhancement in the tissue absorption
      coefficient of about 25%-50% as compared with the initial, static value. In
      addition, the model predicts an increase in the tissue ablation rate as corneal
      hydration increases, which may provide additional insight into variations in
      refractive surgery outcome.

PMID- 17206245
TI  - Multilevel isotrigon textures.
AB  - To date a small palette of isotrigon textures have been available to study how
      the brain uses higher-order spatial correlation information. We introduce several
      hundred new isotrigon textures. Special modulation properties are illustrated
      that can be used to extract neural responses to higher-order spatial
      correlations. We also ask how many textures make an adequate training set and how
      representative individual examples are of their texture class. Human
      discrimination of 90 of these patterns was quantified. Modeling those responses
      shows that humanlike performance can be obtained providing a fourth-order
      classifier is used, although more than one mechanism is required.

PMID- 17206246
TI  - Analytic solution for separating spectra into illumination and surface
      reflectance components.
AB  - The measured light spectrum is the result of an illuminant interacting with a
      surface. The illuminant spectral power distribution multiplies the surface
      spectral reflectance function to form a color signal--the light spectrum that
      gives rise to our perception. Disambiguation of the two factors, illuminant and
      surface, is difficult without prior knowledge. Previously [IEEE Trans. Pattern
      Anal. Mach. Intell.12, 966 (1990); J. Opt. Soc. Am. A21, 1825 (2004)], one
      approach to this problem applied a finite-dimensional basis function model to
      recover the separate illuminant and surface reflectance components that make up
      the color signal, using principal component bases for lights and for
      reflectances. We introduce the idea of making use of finite-dimensional models of
      logarithms of spectra for this problem. Recognizing that multiplications turn
      into additions in such a formulation, we can replace the original iterative
      method with a direct, analytic algorithm with no iteration, resulting in a
      speedup of several orders of magnitude. Moreover, in the new, logarithm-based
      approach, it is straightforward to further design new basis functions, for both
      illuminant and reflectance simultaneously, such that the initial basis function
      coefficients derived from the input color signal are optimally mapped onto
      separate coefficients that produce spectra that more closely approximate the
      illuminant and the surface reflectance for any given dimensionality. This is
      accomplished by using an extra bias correction step that maps the analytically
      determined basis function coefficients onto the optimal coefficient set,
      separately for lights and surfaces, for the training set. The analytic equation
      plus the bias correction is then used for unknown input color signals.

PMID- 17206247
TI  - Probe transit effect in interferometry of fast moving samples.
AB  - When a fast moving transparent sample (with a speed close to c) is probed with a
      laser pulse, some artifacts can occur from data analysis. These artifacts are
      connected to the transit time of the probe through the sample and can mask the
      presence of a steep gradient of refractive index in the sample. We study this
      problem in the case of interferometry. In fact, the problem can affect the
      femtosecond interferometry of the media under ultrafast ionization by a
      propagating laser pulse. Two algorithms are introduced: the first based on the
      phase difference and the second based on visibility. Both algorithms allow for
      the reconstruction, under suitable assumptions, of an approximated refractive
      index profile from the distorted fringes.

PMID- 17206248
TI  - Digital superresolution and the generalized sampling theorem.
AB  - The technique of reconstructing a higher-resolution (HR) image of size MLxML by
      digitally processing LxL subpixel-shifted lower-resolution (LR) copies of it,
      each of size MxM, has now become well established. This particular digital
      superresolution problem is analyzed from the standpoint of the generalized
      sampling theorem. It is shown both theoretically and by computer simulation that
      the choice of regularly spaced subpixel shifts for the LR images tends to
      maximize the robustness and minimize the error of reconstruction of the HR image.
      In practice, since subpixel-level control of LR image shifts may be nearly
      impossible to achieve, however, a more likely scenario, which is also discussed,
      is one involving random subpixel shifts. It is shown that without reasonably
      tight bounds on the range of random shifts, the reconstruction is likely to fail
      in the presence of even small amounts of noise unless either reliable prior
      information or additional data are available.

PMID- 17206249
TI  - Error analysis in inverse scatterometry. I. Modeling.
AB  - Scatterometry is an optical technique that has been studied and tested in recent
      years in semiconductor fabrication metrology for critical dimensions. Previous
      work presented an iterative linearized method to retrieve surface-relief profile
      parameters from reflectance measurements upon diffraction. With the iterative
      linear solution model in this work, rigorous models are developed to represent
      the random and deterministic or offset errors in scatterometric measurements. The
      propagation of different types of error from the measurement data to the profile
      parameter estimates is then presented. The improvement in solution accuracies is
      then demonstrated with theoretical and experimental data by adjusting for the
      offset errors. In a companion paper (in process) an improved optimization method
      is presented to account for unknown offset errors in the measurements based on
      the offset error model.

PMID- 17206250
TI  - Single-scattering theory of light diffraction by a circular subwavelength
      aperture in a finitely conducting screen.
AB  - A perturbation theory based on a single-scattering approximation is developed
      from the rigorous differential theory of diffraction in cylindrical coordinates.
      It results in analytical formulas in the inverse space for the field amplitudes
      providing results that are in quantitative agreement with the results of the
      rigorous method, in both the near- and far-field regions, when a proper
      correction to the incident field inside the aperture is made by using the
      renormalized Born approximation. When working in reflection by a screen having
      permittivity high in modulus, the method proposes an equivalence with the simple
      model consisting of the emission by a single magnetic dipole excited inside the
      pierced layer, emission that is then transferred back into the cladding following
      the Fresnel's coefficients of transmission from the layer into the cladding. The
      theory predicts a directivity of the radiation pattern that increases for smaller
      values of modulus of permittivity, both for dielectrics and metals, thus
      independently of the possibility of plasmon surface wave excitation along the
      interface. The theory can take into account such surface wave resonances, as well
      as the waveguide supported by a dielectric slab, but cannot implicitly recognize
      the modes carried out by the cylindrical waveguide corresponding to the aperture.
      This fact limits its domain of validity when used in transmission, although the
      far- and near-field maps can be reconstructed sufficiently well within a
      multiplicative factor corresponding to the enhanced transmission due to the
      excitation of these modes.

PMID- 17206251
TI  - Exact analysis of the effects of sampling of the scalar diffraction field.
AB  - If the sampled diffraction pattern due to a planar object is used to reconstruct
      the object pattern by backpropagation, the obtained pattern is no longer the same
      as the original. The effect of such sampling on the reconstruction is analyzed.
      The formulation uses the plane-wave expansion, and therefore the provided
      solution is exact for wave propagation in media where scalar wave propagation is
      valid. In contrast to the sampling effects under the Fresnel approximation, the
      exact solution indicates that there are no modulated replicas of the original
      object in the reconstructed pattern. Rather, the distortion is in the form of
      modulated, translated, and dispersed versions of the original.

PMID- 17206252
TI  - Propagation theories of arbitrary-order correlations of partially coherent
      electromagnetic fields based on separated-coordinate mode decomposition.
AB  - Theories to calculate the propagation of arbitrary-order correlations of
      stationary or nonstationary partially coherent electromagnetic fields are
      proposed. The theories are based on separated-coordinate mode decomposition, and
      can make the well-developed propagation theories of fully coherent
      electromagnetic fields applicable to partially coherent electromagnetic fields
      governed by linear Maxwell equations. The validity of the theories is illustrated
      by an example.

PMID- 17206253
TI  - Optical properties of a square-lattice photonic crystal within the partial
      bandgap.
AB  - Optical properties of a two-dimensional square-lattice photonic crystal are
      systematically investigated within the partial bandgap through anisotropic
      characteristics analysis and numerical simulation of field pattern. Using the
      plane-wave expansion method and Hellmann-Feynman theorem, the relationships
      between the incident and refracted angles for both phase and group velocities are
      calculated to analyze light propagation from air to photonic crystals. Three
      kinds of flat slab focusing are summarized and demonstrated by numerical
      simulations using the multiple scattering method.

PMID- 17206254
TI  - Separation of surface and volume effects in scattering from heterogeneous rough
      surfaces: derivation of a splitting rule.
AB  - We give theoretical support to the splitting rule, which was recently observed
      numerically for the scattering from heterogeneous rough surfaces. Under certain
      general conditions, the incoherent intensity of a composite medium with a rough
      interface is the sum of the incoherent intensity of the rough homogeneous surface
      with an effective permittivity and the incoherent intensity of the same composite
      medium below a flat interface. The coherent intensity is merely that of the rough
      effective homogeneous surface. The effective permittivity is given accurately by
      the Bruggemann mixing rule, provided that the scale of fluctuations in the volume
      is small with respect to the electromagnetic wavelength.

PMID- 17206255
TI  - Maximum-likelihood methods in wavefront sensing: stochastic models and likelihood
      functions.
AB  - Maximum-likelihood (ML) estimation in wavefront sensing requires careful
      attention to all noise sources and all factors that influence the sensor data. We
      present detailed probability density functions for the output of the image
      detector in a wavefront sensor, conditional not only on wavefront parameters but
      also on various nuisance parameters. Practical ways of dealing with nuisance
      parameters are described, and final expressions for likelihoods and Fisher
      information matrices are derived. The theory is illustrated by discussing Shack
      Hartmann sensors, and computational requirements are discussed. Simulation
      results show that ML estimation can significantly increase the dynamic range of a
      Shack-Hartmann sensor with four detectors and that it can reduce the residual
      wavefront error when compared with traditional methods.

PMID- 17206256
TI  - Closed-form approximations for the angle-of-arrival variance of plane and
      spherical waves propagating through homogeneous and isotropic turbulence.
AB  - The calculation of the aperture-averaged angle-of-arrival variance, observed with
      a telescope with a circular aperture, of a plane or spherical wave propagating
      through homogeneous and isotropic turbulence is one of the classical problems in
      the theory of wave propagation through random media. We present and discuss
      approximate closed-form solutions on the basis of the Rytov approximation. For
      both plane and spherical waves, the accuracy of the approximations is better than
      0.25% for all ratios of aperture diameter and Fresnel length.

PMID- 17206257
TI  - Numerical study on the validity of the diffusion approximation for computational
      optical biopsy.
AB  - Currently, we are developing a computational optical biopsy technology for
      molecular sensing. We use the diffusion equation to model photon propagation but
      have a concern about the accuracy of diffusion approximation when the optical
      sensor is close to a bioluminescent source. We derive formulas to describe photon
      fluence for point and ball sources and measurement formulas for an idealized
      optical biopsy probe. Then, we numerically compare the diffusion approximation
      and the radiative transport as implemented by Monte Carlo simulation in the cases
      of point and ball sources. Our simulation results show that the diffusion
      approximation can be accurately applied if mu's>>mu(a) even if the sensor is very
      close to the source (>1mm). Furthermore, an approximate formula is given to
      describe the measurement of a cut-end fiber probe for a ball source.

PMID- 17206258
TI  - Optical trapping of spheroidal particles in Gaussian beams.
AB  - The T matrix method is used to compute equilibrium positions and orientations for
      spheroidal particles trapped in Gaussian light beams. It is observed that there
      is a qualitative difference between the behavior of prolate and oblate ellipsoids
      in linearly polarized Gaussian beams; the former generally orient with the
      symmetry axis parallel to the beam except at very small particle sizes, while the
      latter orient with the symmetry axis perpendicular to the beam. In the presence
      of a circularly polarized beam, it is demonstrated that oblate ellipsoids will
      experience a torque about the beam axis. However, for a limited range of particle
      sizes, where the particle dimensions are comparable with the beam waist, the
      particles are predicted to rotate in a sense counter to the sense of rotation of
      the circular polarization. This unusual prediction is discussed in some detail.

PMID- 17206259
TI  - Propagation of elliptical Gaussian beams modulated by an elliptical annular
      aperture.
AB  - An analytical propagation expression for a generalized astigmatic elliptical
      Gaussian beam (EGB) modulated by an elliptical annular aperture and passing
      through an axially nonsymmetrical optical system is obtained by the use of vector
      integration. The derived analytical results provide more convenience for studying
      the propagation and transformation of EGBs than the usual method of using the
      diffraction integral directly, and the efficiency of the numerical calculation is
      significantly improved. Some numerical simulations are illustrated for the
      propagation properties of EGBs passing through a free space with an elliptical
      annular aperture, an elliptical screen, or an elliptical aperture. Further
      extensions are also pointed out.

PMID- 17206260
TI  - Comparison of geometric optics approximation and integral method for reflection
      and transmission from microgeometrical dielectric surfaces.
AB  - The effects of incidence angle, geometrical shape, and optical properties of
      dielectric rough surfaces on reflectivity and transmissivity are discussed.
      Radiative properties for various surface geometries are calculated. Since the
      integral method is computationally expensive, a geometric optics approximation is
      developed. The regions of validity of the approximation compared with the
      integral method are quantified. Curves are presented that show these radiative
      properties versus the correlation length at incidence angle for a fixed rms
      deviation of the surface. The surface geometry, incidence angle, multiple
      scattering, shadowing effects, and dielectric permittivity contributions to the
      domains of validity of the approximation method are discussed for both TE and TM
      polarizations.

PMID- 17206261
TI  - Intensity control with a free-form lens.
AB  - A family of free-form lenses for intensity control is designed. The lens can
      shape an incident collimated beam with a given intensity distribution I1 into a
      new collimated beam with intensity distribution I2. No symmetry is assumed for
      the two intensity profiles. The key idea is that the lens design problem can be
      formulated and solved in terms of an optimization process involving a specific
      action functional. It is further shown that the free-form lens can be
      manufactured by a surfacing process using a convex tool.

PMID- 17206262
TI  - Electromagnetic analysis of coupling and guiding phenomena in elliptical cross
      section parallel waveguides with rotated symmetry planes.
AB  - Rigorous electromagnetic analysis methods, based on the Green's function method
      along with the method of moments, are utilized to analyze coupling, guiding, and
      polarization phenomena in elliptic cross-section parallel waveguides. The
      analysis is carried out for the general case of closely spaced elliptic fibers of
      arbitrary orientation of the ellipses' axes. Numerical results are presented for
      the cases of 0 degrees and 45 degrees angles between axes, as well as for the
      single elliptical fiber and closely spaced circular dielectric waveguides. The
      possibility of using this type of coupling structure in quantum signal processing
      applications is examined.

PMID- 17206263
TI  - Dynamics of the linearly polarized fundamental Gaussian light wave.
AB  - A continuous planar array of dipoles that are oriented in a particular direction
      and have an amplitude distribution that is Gaussian in the paraxial limit is
      introduced as a source for the fundamental Gaussian light wave. The radiation
      intensity of the Gaussian light wave is determined and its characteristics are
      analyzed. The universal Gaussian beam factor is deduced and identified as the
      radiation intensity of the scalar Gaussian wave. The total radiated power, the
      mean center of the localized wave, and the beam widths of the intensity
      distribution are obtained. The ratio of the power in the Gaussian wave to that in
      the corresponding paraxial Gaussian beam is used as a measure of the quality of
      the paraxial beam approximation. A limiting factor for the power ratio is
      introduced as an indicator for the acceptability of the paraxial beam
      approximation. The cross section and the beam widths of the localized light wave
      are investigated in the large and small kw0 limits, where k is the wavenumber and
      w0 is the beam waist at the input plane. The beam width of the full Gaussian wave
      is found to be less than that of the corresponding paraxial Gaussian beam both
      for the scalar Gaussian wave and for the Gaussian light wave.

PMID- 17206264
TI  - Reflectivity properties of an anisotropic slab waveguide with isolated substrate.
AB  - The scattering properties for both TE and TM modes of an abruptly ended two
      layered slab waveguide with anisotropic core and isolated substrate are examined
      by an improved iteration technique, which is based on the integral equation
      method with accelerating parameters. The relative dielectric constants of the
      core for the three Cartesian directions are considered to be different, but cases
      with isotropic core are also considered. The electric field distribution on the
      terminal plane and the reflection coefficients of the dominant TE and TM guided
      modes, as well as the near-field distribution and the far-field radiation
      pattern, are computed, while numerical results are presented for several cases of
      the core anisotropy.

PMID- 17206265
TI  - Scattering from a cylindrical reflector: modified theory of physical optics
      solution.
AB  - The problem of scattering from a perfectly conducting cylindrical reflector is
      examined with the method of the modified theory of physical optics. In this
      technique the physical optics currents are modified by using a variable unit
      vector on the scatterer's surface. These current components are obtained for the
      reflector, which is fed by an offset electric line source. The scattering
      integral is expressed by using these currents and evaluated asymptotically with
      the stationary phase method. The results are compared numerically by using
      physical optics theory, geometrical optics diffraction theory, and the exact
      solution of the Helmholtz equation. It is found that the modified theory of
      physical optics scattering field equations agrees with the geometrical optics
      diffraction theory and the exact solution of the Helmholtz equation.

PMID- 17206266
TI  - Edge-dislocation waves in the diffraction process by an impedance half-plane.
AB  - Edge-dislocation waves, created in the diffraction of plane waves by an impedance
      half-plane, are examined by the method of modified theory of physical optics. The
      integrals, obtained by a related technique, are decomposed according to their
      boundaries and evaluated by using uniform asymptotic methods. The results are
      plotted and are investigated numerically.

PMID- 17206267
TI  - Rigorous electromagnetic analysis of the common focusing characteristics of a
      cylindrical microlens with long focal depth and under multiwavelength
      illumination.
AB  - The common focusing characteristics of a cylindrical microlens with a long focal
      depth and under a given multiple-wavelength illumination are analyzed based on
      the boundary element method (BEM). The surface-relief profile of a finite
      substrate-thickness microlens with a long focal depth is presented. Its focusing
      performances, such as the common extended focal depth (CEFD), the spot size, and
      the diffraction efficiency, are numerically studied in the case of TE
      polarization. The results show that the CEFD of the microlens increases
      initially, reaches a peak value, and then decreases with increasing preset focal
      depth. Two modified profiles of a finite-substrate-thickness cylindrical
      microlens are proposed for enlarging the CEFD. The rigorous numerical results
      indicate that the modified surface-relief structures of a cylindrical microlens
      can successfully modulate the optical field distribution to achieve longer CEFD,
      higher transverse resolution, and higher diffraction efficiency simultaneously,
      compared with the prototypical microlens. These investigations may provide useful
      information for the design and application of micro-optical elements in various
      multiwavelength optical systems.

PMID- 17206268
TI  - Design method for small-f-number microlenses based on a finite thickness model in
      combination with the Yang-Gu phase-retrieval algorithm.
AB  - We present a fast and general iterative design method for both diffractive and
      nondiffractive two-dimensional optical elements. The method is based on a finite
      thickness model in combination with the Yang-Gu phase-retrieval algorithm. A
      rigorous electromagnetic analysis (boundary element method) is used to appraise
      the designed results. We calculate the transverse-intensity distributions,
      diffraction efficiency, and spot size of the designed microlenses at the focusing
      plane for microlenses designed using the presented method and the conventional
      zero-thickness model. The main findings show the superiority of the presented
      method over the conventional method, especially for nondiffractive optical
      elements.

PMID- 17206269
TI  - Sensitivity analysis of a nanowire-based surface plasmon resonance biosensor in
      the presence of surface roughness.
AB  - We have investigated the effect of surface roughness on the sensitivity of
      conventional and nanowire-based surface plasmon resonance (SPR) biosensors. The
      theoretical research was conducted using rigorous coupled-wave analysis with
      Gaussian surface profiles of gold films determined by atomic force microscopy.
      The results suggest that, when surface roughness ranges near 1 nm, the
      sensitivity of a conventional SPR system is not significantly affected regardless
      of the correlation length. For a nanowire-based SPR biosensor, however, we have
      found that the sensitivity degrades substantially with decreasing correlation
      length. In particular, at a correlation length smaller than 100 nm, a random
      rough surface may induce destructive coupling between excited localized surface
      plasmons, which can lead to prominent reduction of sensitivity enhancement.

PMID- 17206270
TI  - Surface modes at the interfaces between isotropic media and indefinite media.
AB  - Characteristics of surface modes at the interface between an isotropic medium and
      an indefinite medium that has a dispersion relation of hyperbolic form are
      studied. Four cases for the isotropic medium, including normal, left-handed,
      magnetic (with negative permeability), and metallic media, are considered. The
      conditions for the existence of surface modes in each case are analyzed in
      detail, and the results are expressed explicitly, indicating that the existence
      of surface modes is determined by the nature of the indefinite medium as well as
      the orientation of the boundary surface of this anisotropic medium. The energy
      flows associated with the surface modes are also discussed.

PMID- 17206271
TI  - X-ray noninterferometric phase imaging: a unified picture.
AB  - A unified theory of noninterferometric phase recovery based on the so-called
      ambiguity function is introduced. The theory is used to analyze previously
      published techniques and unify them with the methods of phase-space tomography
      applicable to partially coherent data. The theory is then used to propose some
      new approaches to noninterferometric phase recovery.

PMID- 17206272
TI  - Examination of the revised Kubelka-Munk theory: considerations of modeling
      strategies.
AB  - The revised Kubelka-Munk theory is examined theoretically and experimentally.
      Systems of dyed paper sheets are simulated, and the results are compared with
      other models. The results show that the revised Kubelka-Munk model yields
      significant errors in predicted dye-paper mixture reflectances, and is not self
      consistent. The absorption is noticeably overestimated. Theoretical arguments
      show that properties in the revised Kubelka-Munk theory are inadequately derived.
      The main conclusion is that the revised Kubelka-Munk theory is wrong in the
      inclusion of the so-called scattering-induced-path-variation factor.
      Consequently, the theory should not be used for light scattering calculations.
      Instead, the original Kubelka-Munk theory should be used where its accuracy is
      sufficient, and a radiative transfer tool of higher resolution should be used
      where higher accuracy is needed.

PMID- 17206275
TI  - Improvements to the Red List Index.
AB  - The Red List Index uses information from the IUCN Red List to track trends in the
      projected overall extinction risk of sets of species. It has been widely
      recognised as an important component of the suite of indicators needed to measure
      progress towards the international target of significantly reducing the rate of
      biodiversity loss by 2010. However, further application of the RLI (to non-avian
      taxa in particular) has revealed some shortcomings in the original formula and
      approach: It performs inappropriately when a value of zero is reached; RLI values
      are affected by the frequency of assessments; and newly evaluated species may
      introduce bias. Here we propose a revision to the formula, and recommend how it
      should be applied in order to overcome these shortcomings. Two additional
      advantages of the revisions are that assessment errors are not propagated through
      time, and the overall level extinction risk can be determined as well as trends
      in this over time.

PMID- 17206274
TI  - Rapid dissemination of Plasmodium falciparum drug resistance despite strictly
      controlled antimalarial use.
AB  - BACKGROUND: Inadequate treatment practices with antimalarials are considered
      major contributors to Plasmodium falciparum resistance to chloroquine,
      pyrimethamine and sulfadoxine. The longitudinal survey conducted in Dielmo, a
      rural Senegalese community, offers a unique frame to explore the impact of
      strictly controlled and quantified antimalarial use for diagnosed malaria on drug
      resistance. METHODOLOGY/PRINCIPAL FINDINGS: We conducted on a yearly basis a
      retrospective survey over a ten-year period that included two successive
      treatment policies, namely quinine during 1990-1994, and chloroquine (CQ) and
      sulfadoxine/pyrimethamine (SP) as first and second line treatments, respectively,
      during 1995-1999. Molecular beacon-based genotyping, gene sequencing and
      microsatellite analysis showed a low prevalence of Pfcrt and Pfdhfr-ts resistance
      alleles of Southeast Asian origin by the end of 1994 and their effective
      dissemination within one year of CQ and SP implementation. The Pfcrt resistant
      allele rose from 9% to 46% prevalence during the first year of CQ reintroduction,
      i.e., after a mean of 1.66 CQ treatment courses/person/year. The Pfdhfr-ts triple
      mutant rose from 0% to 20% by end 1996, after a mean of 0.35 SP treatment
      courses/person in a 16-month period. Both resistance alleles were observed at a
      younger age than all other alleles. Their spreading was associated with enhanced
      in vitro resistance and rapidly translated in an increased incidence of clinical
      malaria episodes during the early post-treatment period. CONCLUSION/SIGNIFICANCE:
      In such a highly endemic setting, selection of drug-resistant parasites took a
      single year after drug implementation, resulting in a rapid progression of the
      incidence of clinical malaria during the early post-treatment period. Controlled
      antimalarial use at the community level did not prevent dissemination of
      resistance haplotypes. This data pleads against reintroduction of CQ in places
      where resistant allele frequency has dropped to a very low level after CQ use has
      been discontinued, unless drastic measures are put in place to prevent selection
      and spreading of mutants during the post-treatment period.

PMID- 17206276
TI  - Intron dynamics in ribosomal protein genes.
AB  - The role of spliceosomal introns in eukaryotic genomes remains obscure. A large
      scale analysis of intron presence/absence patterns in many gene families and
      species is a necessary step to clarify the role of these introns. In this
      analysis, we used a maximum likelihood method to reconstruct the evolution of
      2,961 introns in a dataset of 76 ribosomal protein genes from 22 eukaryotes and
      validated the results by a maximum parsimony method. Our results show that the
      trends of intron gain and loss differed across species in a given kingdom but
      appeared to be consistent within subphyla. Most subphyla in the dataset diverged
      around 1 billion years ago, when the "Big Bang" radiation occurred. We speculate
      that spliceosomal introns may play a role in the explosion of many eukaryotes at
      the Big Bang radiation.

PMID- 17206278
TI  - The waiting time for inter-country spread of pandemic influenza.
AB  - BACKGROUND: The time delay between the start of an influenza pandemic and its
      subsequent initiation in other countries is highly relevant to preparedness
      planning. We quantify the distribution of this random time in terms of the
      separate components of this delay, and assess how the delay may be extended by
      non-pharmaceutical interventions. METHODS AND FINDINGS: The model constructed for
      this time delay accounts for: (i) epidemic growth in the source region, (ii) the
      delay until an infected individual from the source region seeks to travel to an
      at-risk country, (iii) the chance that infected travelers are detected by
      screening at exit and entry borders, (iv) the possibility of in-flight
      transmission, (v) the chance that an infected arrival might not initiate an
      epidemic, and (vi) the delay until infection in the at-risk country gathers
      momentum. Efforts that reduce the disease reproduction number in the source
      region below two and severe travel restrictions are most effective for delaying a
      local epidemic, and under favourable circumstances, could add several months to
      the delay. On the other hand, the model predicts that border screening for
      symptomatic infection, wearing a protective mask during travel, promoting early
      presentation of cases arising among arriving passengers and moderate reduction in
      travel volumes increase the delay only by a matter of days or weeks. Elevated in
      flight transmission reduces the delay only minimally. CONCLUSIONS: The delay
      until an epidemic of pandemic strain influenza is imported into an at-risk
      country is largely determined by the course of the epidemic in the source region
      and the number of travelers attempting to enter the at-risk country, and is
      little affected by non-pharmaceutical interventions targeting these travelers.
      Short of preventing international travel altogether, eradicating a nascent
      pandemic in the source region appears to be the only reliable method of
      preventing country-to-country spread of a pandemic strain of influenza.

PMID- 17206277
TI  - Wingless directly represses DPP morphogen expression via an armadillo/TCF/Brinker
      complex.
AB  - BACKGROUND: Spatially restricted morphogen expression drives many patterning and
      regeneration processes, but how is the pattern of morphogen expression
      established and maintained? Patterning of Drosophila leg imaginal discs requires
      expression of the DPP morphogen dorsally and the wingless (WG) morphogen
      ventrally. We have shown that these mutually exclusive patterns of expression are
      controlled by a self-organizing system of feedback loops that involve WG and DPP,
      but whether the feedback is direct or indirect is not known. METHODS/FINDINGS: By
      analyzing expression patterns of regulatory DNA driving reporter genes in
      different genetic backgrounds, we identify a key component of this system by
      showing that WG directly represses transcription of the dpp gene in the ventral
      leg disc. Repression of dpp requires a tri-partite complex of the WG mediators
      armadillo (ARM) and dTCF, and the co-repressor Brinker, (BRK), wherein ARM.dTCF
      and BRK bind to independent sites within the dpp locus. CONCLUSIONS/SIGNIFICANCE:
      Many examples of dTCF repression in the absence of WNT signaling have been
      described, but few examples of signal-driven repression requiring both ARM and
      dTCF binding have been reported. Thus, our findings represent a new mode of WG
      mediated repression and demonstrate that direct regulation between morphogen
      signaling pathways can contribute to a robust self-organizing system capable of
      dynamically maintaining territories of morphogen expression.

PMID- 17206279
TI  - Relationship between thermodynamic driving force and one-way fluxes in reversible
      processes.
AB  - Chemical reaction systems operating in nonequilibrium open-system states arise in
      a great number of contexts, including the study of living organisms, in which
      chemical reactions, in general, are far from equilibrium. Here we introduce a
      theorem that relates forward and reverse fluxes and free energy for any chemical
      process operating in a steady state. This relationship, which is a generalization
      of equilibrium conditions to the case of a chemical process occurring in a
      nonequilibrium steady state in dilute solution, provides a novel equivalent
      definition for chemical reaction free energy. In addition, it is shown that
      previously unrelated theories introduced by Ussing and Hodgkin and Huxley for
      transport of ions across membranes, Hill for catalytic cycle fluxes, and Crooks
      for entropy production in microscopically reversible systems, are united in a
      common framework based on this relationship.

PMID- 17206280
TI  - Heterologous tissue culture expression signature predicts human breast cancer
      prognosis.
AB  - BACKGROUND: Cancer patients have highly variable clinical outcomes owing to many
      factors, among which are genes that determine the likelihood of invasion and
      metastasis. This predisposition can be reflected in the gene expression pattern
      of the primary tumor, which may predict outcomes and guide the choice of
      treatment better than other clinical predictors. METHODOLOGY/PRINCIPAL FINDINGS:
      We developed an mRNA expression-based model that can predict prognosis/outcomes
      of human breast cancer patients regardless of microarray platform and patient
      group. Our model was developed using genes differentially expressed in mouse
      plasma cell tumors growing in vivo versus those growing in vitro. The prediction
      system was validated using published data from three cohorts of patients for whom
      microarray and clinical data had been compiled. The model stratified patients
      into four independent survival groups (BEST, GOOD, BAD, and WORST: log-rank test
      p = 1.7x10(-8)). CONCLUSIONS: Our model significantly improved the survival
      prediction over other expression-based models and permitted recognition of
      patients with different prognoses within the estrogen receptor-positive group and
      within a single pathological tumor class. Basing our predictor on a dataset that
      originated in a different species and a different cell type may have rendered it
      less sensitive to proliferation differences and endowed it with wide
      applicability. SIGNIFICANCE: Prognosis prediction for patients with breast cancer
      is currently based on histopathological typing and estrogen receptor positivity.
      Yet both assays define groups that are heterogeneous in survival. Gene expression
      profiling allows subdivision of these groups and recognition of patients whose
      tumors are very unlikely to be lethal and those with much grimmer outlooks, which
      can augment the predictive power of conventional tumor analysis and aid the
      clinician in choosing relaxed vs. aggressive therapy.

PMID- 17206283
TI  - Hereditary hemorrhagic telangiectasia. Genetics, pathogenesis, clinical
      manifestation and management.
AB  - Hereditary hemorrhagic telangiectasia HHT, Morbus Osler or Osler-Weber-Rendu
      syndrome OMIM 187300, is an autosomal dominant disorder characterized by
      epistaxis, telangiectasia, multi-systemic vascular dysplasia and clinical
      presentation of wide variation. The pathogenesis involves dilated post-capillary
      venules or telangiectases in the mucus membrane of various organs as well as
      larger arteriovenous malformations. Genetic heterogeneity of HHT is confirmed; 2
      disease loci, ACVRL1 and ENG genes, have been identified and characterized. The 2
      major types of the disease, HHT1 and HHT2, are attributed to mutations in the ENG
      and ACVRL1 genes. ENG and ACVRL1 genes code for proteins, namely endoglin and
      activin-receptor-like kinase 1 ALK-1, which are members of the TGF-beta receptor
      family, are essential for maintaining vascular integrity. Another gene has been
      implicated in HHT; the HHT3 locus linked to chromosome 5. In the last 2 decades,
      the genetics, pathogenesis, clinical manifestations and management of HHT have
      been extensively researched. At this stage, it is deemed appropriate to review
      the wealth of information accumulated on the topic. Better understanding of the
      functions of endoglin, ALK-1, and other proteins involved in the pathogenesis of
      HHT should facilitate better management of patients with this disorder.

PMID- 17206281
TI  - At-risk and recent-onset type 1 diabetic subjects have increased apoptosis in the
      CD4+CD25+ T-cell fraction.
AB  - BACKGROUND: In experimental models, Type 1 diabetes T1D can be prevented by
      adoptive transfer of CD4+CD25+ (FoxP3+) suppressor or regulatory T cells. Recent
      studies have found a suppression defect of CD4+CD25+(high) T cells in human
      disease. In this study we measure apoptosis of CD4+CD25+(high) T cells to see if
      it could contribute to reduced suppressive activity of these cells. METHODS AND
      FINDINGS: T-cell apoptosis was evaluated in children and adolescent 35 females/40
      males subjects comprising recent-onset and long-standing T1D subjects and their
      first-degree relatives, who are at variable risk to develop T1D. YOPRO1/7AAD and
      intracellular staining of the active form of caspase 3 were used to evaluate
      apoptosis. Isolated CD4+CD25+(high) and CD4+CD25- T cells were co-cultured in a
      suppression assay to assess the function of the former cells. We found that
      recent-onset T1D subjects show increased apoptosis of CD4+CD25+(high) T cells
      when compared to both control and long-standing T1D subjects p<0.0001 for both
      groups. Subjects at high risk for developing T1D 2-3Ab+ve show a similar trend
      p<0.02 and p<0.01, respectively. On the contrary, in long-standing T1D and T2D
      subjects, CD4+CD25+(high) T cell apoptosis is at the same level as in control
      subjects p = NS. Simultaneous intracellular staining of the active form of
      caspase 3 and FoxP3 confirmed recent-onset FoxP3+ve CD4+CD25+(high) T cells
      committed to apoptosis at a higher percentage 15.3+/-2.2 compared to FoxP3+ve
      CD4+CD25+(high) T cells in control subjects 6.1+/-1.7 p<0.002. Compared to
      control subjects, both recent-onset T1D and high at-risk subjects had
      significantly decreased function of CD4+CD25+(high) T cells p = 0.0007 and p =
      0.007, respectively. CONCLUSIONS: There is a higher level of ongoing apoptosis in
      CD4+CD25+(high) T cells in recent-onset T1D subjects and in subjects at high risk
      for the disease. This high level of CD4+CD25+(high) T-cell apoptosis could be a
      contributing factor to markedly decreased suppressive potential of these cells in
      recent-onset T1D subjects.

PMID- 17206284
TI  - Prevalence of extended-spectrum beta-lactamases-producing isolates over a 1-year
      period at a University Hospital in Oman.
AB  - OBJECTIVE: To evaluate the prevalence of extended-spectrum beta-lactamases
      isolates over one year period at Sultan Qaboos University Hospital. METHODS: We
      identified the ESBL isolates during a 12-month period from July 2004 to June
      2005, using a commercial system, and confirmed the result using the National
      Committee for Clinical Laboratory Standards-approved double-disk diffusion
      method. RESULTS: Sensitivity was recorded for a wide range of antibiotics,
      aminoglycosides, carbapenem, cephalosporins, quinolones, aztreonam, ampicillin,
      amoxicillin/clavulanate, ampicillin/sulbactam, piperacillin-tazobactam,
      trimethoprim/ sulfamethoxazole and nitrofurantoin. Of the total ESBL isolated,
      29.6% were from medical ward, followed by outpatients clinic, 24.3%. Urine was
      the main source of ESBLs 70.4%, followed by 16.5% from blood. We observed a 100%
      sensitivity to carbapenems, whereas 93.9% of the isolates were susceptible to
      amikacin. Cephalosporins were 100% resistant, except for cefoxitin, which
      demonstrated sensitivity of 77.4%. Aztreonam, ampicillin, co-amoxyclav and
      ampicillin/sulbactam were 100% resistant. Of the isolates, 57.4% were sensitive
      to nitrofurantoin, whereas Tazocin showed 49.6% sensitivity and co-trimoxazole
      13.9%. To quinolones, 74.8% of the isolates were resistant. CONCLUSION: Excess
      use of third generation cephalosporins led to increase rate of ESBLs, which are
      difficult to treat. Carbapenem are most reliable for treatment of infections
      caused by ESBL isolates. However, overuse of carbapenem may lead to resistance of
      other gram-negative organisms. Therefore, justifiable use of third-generation
      cephalosporins, will be an effective means of controlling and decreasing the
      spread of ESBL isolates.

PMID- 17206285
TI  - A comparative study of the ultrastructure of submandibular, parotid and exocrine
      pancreas in diabetes and fasting.
AB  - OBJECTIVE: To comparatively analyze the ultrastructural changes in the
      submandibular and parotid glands and in the exocrine pancreas following diabetes
      induced by Streptozotocin exposure and the effects of fasting and insulin
      treatment on these alterations. METHODS: For experimental procedure, we included
      48 Sprague-Dawley type rats in July 2001-March 2002 at Gazi University, Turkey.
      We divided the rats into 8 groups following the infusion of Streptozotocin.
      RESULTS: While the degeneration manifested itself as accumulation of secretions
      within the mucous cells in the submandibular gland, lipid droplets were absent,
      being replaced by vacuolar structures. The parotid gland and exocrine pancreas,
      having similar properties, were affected similarly. Diabetes-induced loss of
      granules was observed in the serous cells in both glands. There was diffuse lipid
      accumulation within these cells. Regarding granule content, we observed the most
      prominent degenerative changes in the parotid gland. While cellular loss was
      observed in neither the submandibular, nor the parotid gland, we noted presence
      of apoptotic cells was noted in the pancreas. State of fasting was found to cause
      alterations within the glands indicating increased activity. While insulin
      treatment was seen to restore the structure to normal in general in both of the 3
      glands. CONCLUSION: This study demonstrated that both of the 3 glands are
      affected by diabetes and concomitant fasting, and this effect manifests itself
      via the granule content.

PMID- 17206286
TI  - Single breath vital capacity induction of anesthesia with 8% sevoflurane versus
      intravenous propofol for laryngeal tube insertion in adults.
AB  - OBJECTIVE: To compare the conditions for laryngeal tube airway insertion obtained
      by the inhalation of 8% sevoflurane using a vital capacity breath (VCB) technique
      with propofol intravenous induction. METHODS: We carried out a prospective,
      randomized, single blind study at King Abdullah University Hospital, Irbid,
      Jordan from September 2005 to April 2006. Involved in this study were 80 adult
      (ASA physical status I and II) patients aged 26-70 years undergoing elective
      surgery under general anesthesia. The patients were randomized into 2 groups. An
      independent observer noted the time to loss of consciousness, the presence of
      adverse events, time to successful laryngeal tube placement and the number of
      attempts needed until a successful laryngeal tube insertion. RESULTS: With the
      single VCB method, sevoflurane produced a loss of consciousness faster than
      propofol did (51.6 +/- 4.4 versus 59.7 +/- 4.9 seconds, p<0.001). The insertion
      of laryngeal tube was faster in the propofol group (77.2 +/- 20.2 versus 122.2 +/
      33.3 seconds, p<0.001) and required fewer attempts (1.2 +/- 0.4 versus 1.6 +/-
      0.7, p<0.02). The overall incidence of complications during the induction of
      anesthesia as well as during the laryngeal tube insertion, especially apnea (42%
      versus 0%; p<0.001), was more frequent in the propofol group (82.5% versus 27.5%;
      p<0.001). CONCLUSION: We conclude that vital capacity breath induction with
      sevoflurane produces a faster loss of consciousness and fewer side effects than
      propofol and efficient for laryngeal tube insertion, but takes slightly longer
      than propofol due to the prolonged jaw tightness.

PMID- 17206287
TI  - Is it necessary to consider obesity when constructing norms for hemoglobin or
      when screening for anemia using hemoglobin levels?
AB  - OBJECTIVE: To assess the relationship of total adiposity and abdominal adiposity
      on hemoglobin levels in Saudi nonpregnant women. METHODS: We carried out this
      cross-sectional study during winter of 2002 (from January to March) in and around
      Abha city, Kingdom of Saudi Arabia. Included in the study were 530 non-pregnant
      women between the age of 18-65 years. Body weight was measured using an Avery
      Beam weighing scale, while height was measured using a stadiometer and waist
      circumference using a fiberglass. Hemoglobin levels were estimated using
      cyanmethemoglobin method. Total obesity was defined as body mass index (BMI)
      >or=30 and abdominal obesity as WC >88 cm. RESULTS: The mean and median
      hemoglobin levels were significantly higher in abdominally obese women compared
      with totally obese (p<0.04 versus <0.02) and non obese ones (p<0.04 versus
      <0.03). No significant differences in the mean and median hemoglobin levels were
      observed when abdominally obese women were compared with both abdominally and
      totally obese ones (p<0.7 for both). The mean and the median hemoglobin levels
      were virtually identical in non-obese and totally obese women. Statistical
      analysis showed that the mean hemoglobin level was positively and significantly
      associated with WC (p<0.005) and negatively and insignificantly associated with
      BMI (p<0.8). CONCLUSION: In view of the positive and significant association
      between abdominal obesity and the mean hemoglobin level in this population,
      abdominal obesity should be considered when constructing norms for hemoglobin or
      when screening for anemia using hemoglobin levels.

PMID- 17206288
TI  - Superficial skin ulcers.
AB  - OBJECTIVE: To determine the underlying cause of superficial skin ulcers over a 15
      year period. METHODS: A retrospective histopathological analysis of 670 cases of
      superficial skin ulcers diagnosed in the Department of Pathology, Ahmadu Bello
      University Teaching Hospital, Zaria, Nigeria from January 1991 to December 2005.
      RESULTS: A total of 670 superficial skin ulcers were analyzed. The male to female
      gender ratio was 409:261(1.5:1.0) and a peak age frequency of 44.3% (297) in the
      5th and 6th decades. Spectrum of lesions encountered was categorized into
      inflammatory, infections, benign and malignant diseases. The malignant lesions
      were 309 (46.1%), non-specific inflammation 302 (45.1%), granulation tissue 25
      (3.7%) and pseudoepitheliomatous hyperplasia 14 (2.1%). A total of 18 (2.7%)
      specific infections were encountered, which included bacterial, fungal and viral
      infection. Benign lesions were 2 (0.3%), comprising of neurofibroma and Bowen's
      disease. The most common malignant lesion was squamous cell carcinoma 203 (30.3%)
      with a male to female ratio of 128:75 (1.7:1.0). Of these, 161 were well
      differentiated tumors. The lower limb was the prevalent site distribution of all
      the ulcers. CONCLUSION: Superficial ulcers may be harbinger of malignant
      diseases. Squamous cell carcinoma remains the most common malignant lesion
      arising from chronic superficial ulcers in our setting. Adequate tissue biopsy
      and early diagnosis may reduce the attendant morbidity of these ulcers.

PMID- 17206290
TI  - Revascularization in patients with severe left ventricular impairment who have
      ischemic heart disease.
AB  - OBJECTIVE: To assess the effect of coronary bypass grafting on left ventricular
      (LV) function, exercise capacity and symptom profile in patients with LV
      impairment and retrospectively evaluate the role of the different factors
      affecting LV. METHODS: A total of 45 patients (33 men, 12 women, mean age 63.49
      +/- 7.38 years) with LV ejection fraction of less than 0.32 were admitted to the
      Istanbul University, Cardiology Institute, Istanbul, Turkey between January 2001
      to June 2003 for coronary bypass operation. Preoperative and postoperative wall
      motion, functional class (New York Heart Association) and risk factors were
      analyzed. RESULTS: We had one perioperative mortality (2.2%) and 2 early
      postoperative mortality (4.4%) due to poor cardiac function. There was a
      significant increase in the mean LV ejection fraction from 26.64 +/- 5.17 to
      32.98 +/- 6.38 (p<0.001) postoperatively. In this group the mean New York Heart
      Association grade improved from 2.07 +/- 0.76 to 1.5 +/- 0.79 (p<0.001).
      Preoperative functional class, congestive heart failure, arrhythmia, age,
      pre/postoperative complications were the main predictors of poor outcome
      following surgical revascularization for ischemic cardiomyopathy. CONCLUSION: In
      patients with severe LV impairment with myocardial hibernation, coronary artery
      bypass grafting improves both global and regional LV function and symptom
      profile. We therefore, recommend a coronary artery bypass grafting as an
      alternative to orthotopic heart transplantation whenever myocardial viability are
      documented.

PMID- 17206289
TI  - Ultra-low dose aprotinin effects on reducing the need for blood transfusion in
      cardiac surgery.
AB  - OBJECTIVE: To assess the effects of ultra-low dose one million kallikrein
      inhibitor units (KIU) of aprotinin on bleeding and the need for transfusion after
      cardiac surgery. METHODS: We carried out this randomized clinical trial on 162
      cardiac surgery patients in Shahid Madani Hospital, Tabriz, Iran from April 2004
      to December 2005. The patients were randomly divided into 2 groups of 81
      individuals. In the aprotinin group, 0.5 million KIU infused before and 0.5
      million KIU during cardiopulmonary bypass. In the placebo group, 100 ml normal
      saline was infused as above. The need to use fresh frozen plasma (FFP), packed
      red blood cells (PRBCs) transfusion during, after operation, the rate of chest
      tubes drainage at 6, 12 and 24 hours after surgery were measured in 2 groups.
      RESULTS: Chest tubes drainage at 6 hours after surgery was 190 +/- 24 ml in the
      aprotinin group and 266 +/- 33 ml in the placebo group (p=0.066). The amount of
      bleeding at 12 and 24 hours was significantly different between 2 groups
      (p=0.048, p=0.009). The frequency of blood products transfusion in the aprotinin
      group was 68% and in the placebo group was 75% (p=0.02). The number of PRBCs and
      FFP units transfused were significantly lower in the aprotinin group (p=0.000,
      p=0.005). Total amount of blood and products transfusion in the aprotinin group
      was 2.56 +/- 0.27 units and in placebo group it was 4.37 +/- 0.27 units
      (p=0.0001). CONCLUSION: Results indicate that the use of one million KIU of
      aprotinin in cardiac surgery is effective in reducing postoperative bleeding and
      transfusion requirements.

PMID- 17206291
TI  - Effects of salmon calcitonin on fracture healing in ovariectomized rats.
AB  - OBJECTIVE: To explore the effects of salmon calcitonin on the healing process of
      osteoporotic fractures in ovariectomized rats. METHODS: We performed this study
      in The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China,
      during the period March 2002 to December 2004. We used 120 female adult Wistar
      rats in this experiment, among which 90 underwent ovariectomy (OVX) and the other
      30 had sham-operation. All rats had their left tibias fractured 3 months later.
      The 90 OVX rats were randomly divided into 3 groups with 30 in each, while the 30
      sham-operated rats served as control group. After the fracture the rats had
      subcutaneous injection of normal saline, salmon calcitonin and estrogen,
      respectively. X-ray film, histological examination, bone mineral density (BMD)
      measurement and biomechanics testing were carried out to evaluate the fracture
      healing. RESULTS: Compared with OVX rats treated with normal saline, the rats
      with salmon calcitonin had significantly higher BMD values in the left tibia,
      higher max torque, shear stress of the left tibia 8 weeks after fracture
      (p<0.05), and presented with stronger callus formation, shorter fracture healing
      time and faster normalization of microstructure of bone trabeculae. CONCLUSION:
      Salmon calcitonin can, not only increase BMD in osteoporotic bone, but also
      enhance the bone biomechanical properties and improve the process of fracture
      healing in fractured osteoporotic bone.

PMID- 17206292
TI  - Morel-Lavallee lesion. Results of surgical drainage with the use of synthetic
      glue.
AB  - OBJECTIVE: To evaluate the results of surgical drainage and use of synthetic glue
      in Morel-Lavallee lesions. METHODS: We treated 7 Morel-Lavallee lesions in Ankara
      Bayindir Hospital, Ankara, Turkey between April 2003 and June 2004. These lesions
      developed in 5 male patients due to crush under a vehicle or a traffic accident.
      The mean age was 32.8 years; range 16-55. All lesions were localized in thigh.
      One patient had surgery due to acetabulum fracture and one had an urological
      operation for urethral rupture. All patients were operated 6-48 hours after the
      injury. After surgical drainage, soft tissues were attached with the use of
      synthetic glue and compressive bandage was applied. We defined healing as the
      loss of fluctuation and elicitation of the normal mobility of the injured skin on
      manual examination. The mean follow-up was 11.6 months (range 8-20 months).
      RESULTS: One patient was operated for acetabulum fracture and had a bilateral
      Morel-Lavallee lesion 2 days after the operation. This patient was reoperated for
      drainage. All lesions were healed with a mean of 5 weeks (range 3-8 weeks). No
      infection, necrosis or recurrences were detected during the follow-up.
      CONCLUSION: Results of the treatment with the use of synthetic glue and surgical
      drainage in Morel-Lavallee lesion are satisfactory with early healing time
      without recurrence.

PMID- 17206293
TI  - Laser prostatectomy versus transurethral resection of prostate in the treatment
      of benign prostatic hyperplasia.
AB  - OBJECTIVE: To assess the effectiveness of laser-prostatectomy compared with
      transurethral resection of prostate (TURP). METHODS: This randomized clinical
      trial with one year follow-up, was conducted on 87 patients with benign prostatic
      hyperplasia (BPH) at Shohada-e-Tajrish Hospital, Tehran, Iran, from 1999 to 2003.
      Fifty-two patients underwent TURP and 35 patients were treated by non-contact
      laser prostatectomy using ND: YAG laser at 40-60 watt power and 13000-29000 jules
      energy settings. RESULTS: Comparing variables of urinary maximum flow and
      residue, changes of urine volume and severity of symptoms during consequent
      periods of 3, 6 and 12 months after the operation in 3 groups revealed that
      differences in maximum urinary flow changes were significant only in the sixth
      month (p<0.05). Also, changes in the severity of symptoms before and after the
      operation showed more decrease in the TURP group during all 3 periods of follow
      up (p=0.01). In the laser prostatectomy group duration of operation (p=0.01),
      amount of fluid used during the operation (p<0.001) and duration of bed rest
      (p<0.001) were less than those of the TURP group. CONCLUSION: Laser prostatectomy
      can decrease duration of operation, duration of bed rest and pathogenesis
      following the operation in patients. Although changes in the severity of symptoms
      are more pronounced in TURP patients, changes in urodynamic indexes are similar
      in both groups.

PMID- 17206294
TI  - Iatrogenic bladder injuries during obstetric and gynecological procedures.
AB  - OBJECTIVE: To review the frequency of iatrogenic bladder injuries (IBI) occurring
      during obstetric and gynecological (OBG) procedures and we report a single center
      experience with these emergency urological consultations and interventions and
      analyze their outcomes and correlate them with the present day trends. METHODS:
      We reviewed retrospectively the relevant data of all IBI during various OBG
      procedures from the Medical Records of Abha Maternity Hospital, the OBG wing of
      Assir Central Hospital, Abha, Saudi Arabia over a period of 4.5 years (September
      2000 to February 2005). Various relevant factors of the injuries were studied
      with their final outcome. RESULTS: Out of the 8,684 OBG procedures carried out
      during this period there were 20 occasions of IBI directly related, with an
      overall incidence of 0.23%. The majority of injuries were seen during obstetric
      procedures (85%) and 15% during gynecological procedures. Notably 90% of them
      were recognized intraoperatively and managed. Concomitant ureteric injury was
      noticed in 20% of the cases. Endourological and surgical options were both used
      in the management. Overall outcomes were very satisfactory, unrelated to the
      site, type or other associated injuries. CONCLUSION: The bladder is the most
      commonly injured organ during OBG interventions. Prompt recognition and repair of
      injuries should be the main goal. Gynecologists should be able to do at least a
      minimum diagnostic cystoscopy in emergency situations. It is well established
      that this can lessen, missing iatrogenic urinary tract injuries in this era of
      increasing gamut of gynecologic surgical and laparoscopic procedures.

PMID- 17206295
TI  - Hypertension in Saudi Arabia.
AB  - OBJECTIVE: To determine the prevalence of hypertension among Saudis of both
      gender, between the ages of 30-70 years in rural as well as urban communities.
      This work is part of a major national study on Coronary Artery Disease in Saudis
      Study (CADISS). METHODS: This is a community-based study conducted by examining
      subjects in the age group of 30-70 years of selected households during a 5-year
      period between 1995 and 2000 in Saudi Arabia. Data were obtained from history
      using a validated questionnaire, and examination including measurement of blood
      pressure. The data were analyzed to provide prevalence of hypertension. Logistic
      regression was used to develop a risk assessment model for prevalence of
      hypertension. RESULTS: The total number of subjects included in the study was
      17,230. The prevalence of hypertension was 26.1% in crude terms. For males, the
      prevalence of hypertension was 28.6%, while for females; the prevalence was
      significantly lower at 23.9% (p<0.001). The urban population showed significantly
      higher prevalence of hypertension of 27.9%, compared to rural population's
      prevalence of 22.4% (p<0.001). The prevalence of CAD among hypertensive patients
      was 8.2%, and 4.5% among normotensive subjects (p<0.001). Increasing weight
      showed significant increase in prevalence of hypertension in a linear
      relationship. CONCLUSION: Hypertension is increasing in prevalence in KSA
      affecting more than one fourth of the adult Saudi population. We recommend
      aggressive management of hypertension as well as screening of adults for
      hypertension early to prevent its damaging consequences if left untreated. Public
      health awareness of simple measures, such as low salt diet, exercise, and
      avoiding obesity, to maintain normal arterial blood pressure need to be
      implemented by health care providers.

PMID- 17206296
TI  - Management of hypertensive patients in primary health care setting, auditing the
      practice.
AB  - OBJECTIVE: To audit the medical care provided to hypertensive patients in a
      health care center in Riyadh, Kingdom of Saudi Arabia (KSA) and determine the
      efficient control of hypertension. METHODS: We carried out this cross-sectional
      study on all patients who visited the Health Care Specialty Center of King Abdul
      Aziz Medical City, Riyadh, KSA for hypertension follow-up during the study period
      from October to December 2004. A representative sample of patients was allocated
      randomly using simple randomization method. All patient's records were reviewed
      for proper recording in a designed form. RESULTS: Out of the 242 records we
      reviewed, 201 were included in the study. The patients' mean age was 58.3 +/-
      12.5 years. All were Saudis and 78.6% were females. Most of them (84.3%) received
      their management at primary care level only. Age, gender, presence of diabetes,
      level of medical care, blood glucose, lipid levels and drugs used for management
      of hypertension were sufficiently recorded. Smoking history, body mass index and
      family history of ischemic heart disease were poorly recorded. Quarter of the
      hypertensive patients was sufficiently controlled. The factors associated with
      poor blood pressure (BP) control were advanced age (p=0.008) and presence of
      diabetes, [odds ratio (95% CI)=2.98 (1.47-6.08)]. CONCLUSION: The study reflects
      the deficiencies in BP control and physicians practice. Introducing a checklist
      or electronic medical records may help the improvement of care. Frequent auditing
      is recommended to ensure the required development.

PMID- 17206297
TI  - The role of renin blockers in the prevention of diabetes.
AB  - OBJECTIVE: To evaluate the role of renin blockers angiotensin converting enzymes
      inhibitors (ACEI) or angiotensin receptor blockers (ARB) in the prevention of
      diabetes. METHODS: We did a meta-analysis using the Cochrane group methodology of
      all available randomized controlled trials (RCTs) that evaluated the role of
      renin blockers in which outcomes of new-onset diabetes was reported. This meta
      analysis was conducted between April 2005-April 2006 at King Faisal Specialist
      Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia. RESULTS: Thirteen
      trials including 91,388 individuals met the inclusion criteria. There was a
      statistically significant reduction in the incidence of new-onset diabetes in
      patients receiving renin blockers compared to other antihypertensive agents
      [relative risks=0.79; 95% confidence interval=0.75-0.84). There was a
      statistically significant reduction in the incidence of new-onset diabetes in
      patients receiving renin-blockers compared to diuretics, conventional
      antihypertensive therapy (diuretics or beta-blockers), and calcium channel
      blockers. CONCLUSION: Renin blockers reduce the incidence of new-onset diabetes
      and should be considered as first line therapy, when indicated, in patients at
      high risk for diabetes.

PMID- 17206298
TI  - Male infertility in Kuwait. Etiologic and therapeutic aspects.
AB  - OBJECTIVE: To evaluate the pathological patterns associated with male infertility
      in Kuwait and to characterize treatment outcome after varicocele repair using
      percutaneous varicocele embolization. METHODS: We carried out a prospective study
      of 64 infertile men in Kuwait between 2001 and 2005. All patients included had
      proven non-obstructive azoospermia or oligospermia (sperm count <20 million/ml).
      All patients underwent ultrasonographic evaluation of the scrotum. Fine needle
      aspiration of the testes was performed on all azoospermic patients. RESULTS: A
      total of 24 (38%) patients were azoospermic while 40 (62%) were oligospermic.
      Sertoli- cell-only pattern was the most common cytopathology associated with
      primary testicular failure. Among the oligospermic patients, 50% had small to
      moderate varicocele. Spermatic vein embolization resulted in a significant rise
      in the mean sperm count from 10.6 +/- 3.8 million/ml to 30.2 +/- 6.8 million/ml
      (p<0.05) in 5 treated oligospermic patients, followed by spontaneous pregnancy in
      2 couples. No effect was seen on azoospermic patients. CONCLUSION: From an
      etiological point of view, we believe that the high incidence of Sertoli cell
      only-syndrome among nationals and residents of a country that underwent a major
      environmental insult strengthens the chances of an environmental role in the
      development of this syndrome. From a management point of view, in cultures where
      in vitro fertilization is either still not widely acceptable or is unaffordable,
      oligospermia with clinical or subclinical varicocele deserves a trial of a low
      risk, out patient procedure, namely, spermatic vein embolization that could
      improve fertility.

PMID- 17206299
TI  - Effect of submersion injury on water safety practice after the event in children,
      Saudi Arabia.
AB  - OBJECTIVE: To bring to light issues surrounding water safety practices and the
      impact of such incidents on these practices in our community. METHODS: We
      conducted a prospective observational study at King Abdul-Aziz Medical City,
      Riyadh, Kingdom of Saudi Arabia of all children <12 years of age presenting with
      submersion injury in the period between January 1999 through December 2004 noting
      the demographics and the pattern of water safety practices prior to and after
      event. RESULTS: A total of 29 patients were included. The majority of incidents
      took place in swimming pools. Water safety practices were lacking in most cases
      as evidenced by the fact that 87% of the victims were not properly supervised at
      the time of the event. None of swimming pools met the required safety
      regulations. Cardiopulmonary resuscitation knowledge was virtually nonexistent.
      The event did not have a positive impact on the water safety practices of the
      affected families. CONCLUSION: Submersion injury is also prevalent in land locked
      areas. Water safety practices are deficient in our community. Submersion injury
      was not enough to have a consistent positive impact on water safety practices of
      the affected families. Much can be carried out to improve water safety and save
      lives.

PMID- 17206300
TI  - Acral lentiginous melanoma versus lentigo maligna melanoma among Iraqi patients.
AB  - OBJECTIVE: To report the different clinical aspects of malignant melanoma and
      their varieties in Iraqi patients. METHODS: We carried out this study in the
      Department of Dermatology and Venereology, Baghdad Teaching Hospital, Baghdad,
      Iraq during the period from 1985-2005. Eighteen patients with malignant melanoma
      were enrolled in this work. The different clinical aspects and histopathological
      examination were determined. RESULTS: The study population consisted of 18
      patients (15 females and 3 males) with a female to male ratio of 5:1. Their ages
      ranged from 12-75 years (mean +/- SD, 43.72 +/- 14.75 years) while the duration
      of the disease ranged between 0.25-5 years (1.98 +/- 1.44 years). The duration of
      acral lentiginous melanoma was 0.5-4 years (2.16 +/- 1.36 years) and in nodular
      type was 0.5-3 years (1.28 +/- 0.90 years), while in lentigo maligna melanoma was
      1.5-5 years (3.37 +/- 1.49 years). Regarding the location and gender of the
      patients affected, 6 cases (all females) were on the acral parts of the body (4
      on the feet, and 2 on the hands), 5 patients (all females) on the face, 5 cases
      (4 females and one male) on the lower legs, while the remaining 2 male cases, was
      on the interscapular region and the other one on the elbow area. CONCLUSION: We
      conclude that malignant melanoma in Iraqi patients is a disease of younger
      females, which presented mainly as acral lentiginous melanoma, nodular melanoma
      and lentigo maligna melanoma and superficial spreading melanoma.

PMID- 17206301
TI  - Pattern of rheumatic heart disease in Southern Yemen.
AB  - OBJECTIVE: To determine the pattern of rheumatic heart disease in Aden city and
      surrounding areas by assessing its frequency distribution, severity and
      complications. METHODS: We conducted this research in a sole regional
      echocardiographic department for Southern Yemen governorates at a referral
      hospital located in Aden city, from January 1999 to December 2003. It was a
      retrospective study focused on echocardiographic findings in 805 patients
      affected by rheumatic heart disease. RESULTS: Out of 805 patients, 383 (47.6%)
      were male and 422 (52.4%) were female (age range, 4-70 years; mean age, 28.6 +/-
      14.5). Heart valve damage was distributed among patients as follow: mitral 459
      (57.1%), aorta 70 (8.7%) and both valves 276 (34.2%); isolated lesions 55.2% and
      multiple 44.8%; mitral regurgitation 464 (57.6%), mitral stenosis 405 (50.3%),
      aortic regurgitation 327 (40.6%) and aortic stenosis 54 (6.7%). All children aged
      less than 10 years had regurgitation. Stenosis and multiple valve lesions
      predominated in adolescents and young adults. Complications were detected in
      20.8% of cases. Pulmonary hypertension was the most common complication (80.4%).
      Lesions with moderate and severe degree were detected in 51% cases. Only 34.8% of
      patients at severe stage were operated. CONCLUSION: Rheumatic heart disease takes
      an aggressive course in Southern Yemen. Children, adolescents and young adults of
      both gender are the victims. Complications appear early with scanty opportunity
      to reach advanced age. There is a little chance for palliative treatment.

PMID- 17206302
TI  - Causes of nosocomial pneumonia and evaluation of risk factors in a university
      hospital in Turkey.
AB  - OBJECTIVE: To determine the incidence, risk factors, mortality rate, and
      organisms causing nosocomial pneumonia (NP). METHODS: We carried out this study
      in the Intensive Care Units (ICUs), General Medical and Surgical wards of Baskent
      University, Training and Research Hospital in Adana, Turkey, between November
      2000 and August 2002. Patients were observed from the time of admission until 48
      hours after discharge from the hospital. RESULTS: In this study, 618 (2.1%)
      nosocomial infections (NIs) were detected in 29778 patients. One hundred and
      fifteen of these infections were NP and investigated with surveillance
      prospectively. The most frequently isolated microorganisms in NP were methicillin
      resistant Staphylococcus aureus (MRSA) 32.8%, Pseudomonas species 21.5%,
      methicillin-sensitive Staphylococcus aureus (MSSA) 10.2%, Klebsiella species
      (9.1%) and Acinetobacter species 5.9%, E. coli; 5.4% (10/186), Streptococcus
      species; 4.8% (9/186), Candida species; 4.8% (9/186), Enterobacter species; 2.7%
      (5/186) and the other bacteria; 2.7%. The predominant pathogens isolated in this
      study were MRSA (33.8%), Pseudomonas species (16.9%) and MSSA (16.9%) in early
      onset pneumonias and MRSA (32.2%), Pseudomonas species (24.0%), and Klebsiella
      species (10.7%) in late-onset pneumonias. CONCLUSION: This study demonstrated
      that the possibility of developing NP, significantly increases with such risk
      factors as decreased level of consciousness, respiratory failure, mechanical
      ventilation and tracheostomy. Each center should know its patients' profile, the
      factors that increase the infection, the antibiotic resistance patterns of
      microorganisms, and the distribution of hospital infections in every department.
      Strategies to prevent both development of antibiotic resistance and spread of
      resistant organisms are necessary.

PMID- 17206303
TI  - BK virus infection in a renal transplant Saudi child.
AB  - BK human polyomavirus BKV causes an asymptomatic primary infection in children,
      but later, establishes latency mainly in the urinary tract. Virus-host
      interactions influencing persistence and pathogenicity are not well-understood.
      We present here a 12-year-old Saudi boy, who had renal transplant in Egypt. Seven
      months later, he was admitted to our Pediatric Nephrology Unit as a case of renal
      impairment. He developed BKV infection, diagnosed and successfully managed in our
      hospital. This case demonstrates the expanding clinical importance of BKV in a
      post renal transplant patient. This virus can be detected in transitional cells
      in the urine decoy cells using cytology. Testing for BKV deoxyribonucleic acid in
      urine and blood is an early detection assay, and can be used as a screening test
      in the early stages. The early reduction of immunosuppression can improve the
      prognosis. No specific antiviral treatment has been established yet. This is the
      first report of detecting BK virus in a Saudi post-transplant child in urine and
      blood specimens by using polymerase chain reaction.

PMID- 17206304
TI  - Sudden onset of herpes zoster following chemotherapy for orbital lymphoma in a
      HIV positive patient.
AB  - We report a 38-year-old HIV positive female, who developed an acute attack of
      herpes zoster HZ involving the mandibular, C2, C3, C4, T1, and T2 dermatomes, 9
      days after the commencement of the first cycle of chemotherapy regimen for non
      Hodgkin's lymphoma NHL. She had developed NHL of the ovary approximately 6 months
      earlier, followed by metastasis to the left orbit resulting in proptosis of the
      left eye. A combination of a positive HIV status, lymphoma, and chemotherapy can
      predispose a patient to an attack of HZ involving many dermatomes.

PMID- 17206305
TI  - Elevated cerebrospinal fluid beta-2 microglobulin as a tumor marker in a patient
      with myeloma of the central nervous system.
AB  - Myeloma involvement of the nervous system is rare. Extensive literature review
      revealed only a few cases reported from different parts of the world. The
      presence of CNS symptoms and detection of plasma cells in the CSF is the usual
      basis of diagnosis. In addition, immunoelectrophoresis and immunofixation for
      detection of monoclonal protein confirm the diagnosis in some cases, while some
      authors used flow cytometry and cytogenetic studies on CSF. Reports of multiple
      myeloma also include unfavorable cytogenetic abnormalities of chromosome 13. We
      report a case with relapsed CNS multiple myeloma with the detection of elevated
      beta-2 microglobulin (beta2M) as a tumor marker in the CSF.

PMID- 17206306
TI  - Pulmonary lymphangioleiomyomatosis.
AB  - A 38-year-old Iraqi female, presented with one-year history of exertional dyspnea
      and exercise intolerance, without systemic or constitutional symptoms. Clinical
      examination revealed bilateral basal crackles with signs suggestive of left side
      pleural effusion, chest x-ray showed left sided pleural effusion, and diffuse
      bilateral basal pulmonary shadowing. Her biochemical analysis, hematological
      tests, electrocardiogram and echocardiography were normal, aspiration of the
      fluid revealed a chylothorax, the radiological shadowing was proved by computed
      tomography scan of the chest to be diffuse cystic lesions involving mostly the
      lower lobes. Open lung biopsy showed dilated lymphatic vessels with surrounding
      inflammatory cells and smooth muscle fibers consistently with the diagnosis of
      pulmonary lymphangioleiomyomatosis LAM.

PMID- 17206307
TI  - Wandering spleen with torsion of the pedicle.
AB  - Wandering spleen is a rare medical entity. It usually occurs at 20-40 years of
      age, and most cases are seen in women. Clinical diagnosis is difficult due to
      lack of symptoms, unless splenic torsion has occurred and clinical symptomatology
      of acute abdomen develops. The diagnosis can be confirmed by imaging techniques.
      Treatment is operative due to complications of splenic infarction. Splenopexy is
      the usual treatment, except for cases of splenic infarction. Splenectomy should
      be carried out when there is no evidence of splenic blood flow after detorsion of
      the spleen and in cases of excessive splenomegaly.

PMID- 17206308
TI  - Breast fibroadenoma in female adolescents.
AB  - Palpable breast masses in pediatric patients are uncommon. Fibroadenoma which
      must be distinguished from malignant tumors is the most frequent breast tumor in
      adolescent girl. Fine needle aspiration FNA biopsy is highly specific in breast
      masses. The final cosmetic result is important when planning the surgical
      excision. Therefore it is mandatory to know preoperative cytology of the mass.
      Five girls who had undergone operation with breast masses between 1999-2004 were
      evaluated retrospectively. The mean age at presentation was 13 years. Each
      patient underwent FNA biopsy before excision. Aspiration cytology of the lump
      showed fibroadenoma confirmed by subsequent histopathology. The breast masses can
      be handled operatively through a circumareolar incision without any complication.
      Protection of the developing breast bud, nipple and areola is as important as
      appropriate excision of the lesion. Cosmetic results have been satisfactory and
      there has been no evidence of recurrence.

PMID- 17206309
TI  - Placenta percreta with bladder invasion. A plea for multidisciplinary approach.
AB  - Placenta previa percreta with the urinary bladder invasion is a rare but
      potentially lethal condition. It has an increasing clinical significance due to
      its association with previous cesarean sections and uterine curettage. Herein, we
      report on a patient with placenta percreta and bladder invasion, who presented
      with hematuria and in whom delivery was delayed to almost full term highlighting
      the potential catastrophic results and the need for a multidisciplinary approach
      with the need to involve surgeons who are familiar with vascular and urologic
      surgery. We also present an elegant MRI of placenta percreta invading the urinary
      bladder, which shows that MRI is potentially an excellent diagnostic modality in
      this difficult condition.

PMID- 17206310
TI  - Can worms cause chest pain?

PMID- 17206311
TI  - Percutaneous multiple K-wire fixation for humeral shaft fractures.

PMID- 17206312
TI  - Negative suction versus non-negative suction after coronary surgery.

PMID- 17206313
TI  - Amyloid-depositing plasmacytoma of cervical spine masquerades as a granulomatous
      inflammatory reaction.

PMID- 17206314
TI  - Maternal and fetal thyroid stimulating hormones and the fetal indices of
      maturation, growth, and development.

PMID- 17206315
TI  - A 36-year-old man with palpitation.

PMID- 17206316
TI  - Accuracy of clinical diagnosis versus echocardiography in evaluating heart
      murmurs. How to measure accuracy?

PMID- 17206317
TI  - Loss of body weight and changes of lipid profile.

PMID- 17206318
TI  - White book on Physical and Rehabilitation Medicine in Europe.

PMID- 17206343
TI  - [Oral steroids effects on the respiratory muscles function in severe asthmatic
      patients].
AB  - INTRODUCTION: Several studies suggest that severe asthmatic patients under oral
      steroids show higher risk of myopathy induced by steroids. Nevertheless, no
      conclusive data exist about the prolonged oral steroid therapy effects on the res
      piratory muscles function. We didn't found correlation between the severity of
      obs- truction (evaluated by FEV1), hyperinflation (residual volu- me- RV) and the
      muscle pressures in both groups. Also, there were no significant correlation
      between the G1 PImax and oral steroid accumulated dose. CONCLUSION: We found a
      significant compromise of the res- piratory muscle function in the both studied
      groups with severe asthma. The oral steroid therapy caused no additional adverse
      effect in muscle respiratory function even after a prolon- ged treatment. The
      compromise of the muscle respiratory function foun- ded can be justified by the
      prolonged exposition to inhaled steroids. Key-words: Asthma, respiratory muscles,
      oral steroids.

PMID- 17206368
TI  - Expression and characterization of recombinant human micro-plasminogen.
AB  - Micro-plasminogen (microPlg) gene amplified from human liver cells by reverse
      transcription PCR was inserted into expression vector pET-28a (pET-28a/microPlg)
      and transformed into E. coli strain BL21(DE3). Recombinant human micro
      plasminogen (rh-microPlg) was over-expressed as inclusion bodies when induced
      with IPTG. After renaturation and purification, 16 mg rh-microPlg/l was obtained
      with a homogeneity of 95% (w/w). Pro-urokinase (proUK)-induced rh-microPlg
      activation was significantly faster than when Glu-plasminogen was the substrate.
      The catalytic efficiency of urokinase (UK) activation of rh-microPlg was twice
      that of Glu-plasminogen. While recombinant human micro-plasmin (rh-microPlm) and
      Lys-plasmin had a similar amidolytic activity against a small substrate, D-valyl
      L-leucyllysine-p-nitroaniline dihydrochloride, Lys-plasmin activated proUK with a
      catalytic efficiency about fourfold greater than did rh-microPlm. These results
      suggested that the kringle 1-5 domain of plasminogen and plasmin may modify both
      UK activation of plasminogen and plasmin activation of proUK, respectively.

PMID- 17206369
TI  - Antioxidant properties of dihydroherbimycin A from a newly isolated Streptomyces
      sp.
AB  - During antioxidant screening using 1,1-diphenyl-picrylhydrazyl (DPPH) and a lipid
      peroxidation assay, a streptomycete strain was found to produce herbimycin A and
      dihydroherbimycin A as antioxidants in the culture filtrate. These molecules were
      identified by using spectral analyses, including infrared, ultraviolet, mass
      spectrum, and nuclear magnetic resonance assays. In the DPPH radical-scavenging
      assay, dihydroherbimycin A exhibited more potent antioxidant activity (IC(50),
      1.3 microM) than alpha-tocopherol (IC(50), 2.7 microM) that was used as a
      reference compound. In the lipid peroxidation assay, both herbimycin A and
      dihydroherbimycin A demonstrated antioxidant activities of 61% and 72%,
      respectively, at 100 microg/ml, while alpha-tocopherol exhibited an activity of
      93% at the same concentration. Therefore, dihydroherbimycin A might have the
      potential to be developed into a new therapeutic agent.

PMID- 17206370
TI  - Expression of xylanase with high specific activity from Streptomyces
      olivaceoviridis A1 in transgenic potato plants (Solanum tuberosum L.).
AB  - The gene, xynB, from Streptomyces olivaceoviridis A1 encoding xylanase, XYNB,
      with a high specific activity for xylan, was transformed into potato (Solanum
      tuberosum L.) by Agrobacterium tumefaciens. The integration of xynB into genomic
      DNA was confirmed by PCR and reverse transcriptase-PCR. The gene was expressed
      under the control of a constitutive double cauliflower mosaic virus (CaMV) 35S
      promoter. Both SDS-PAGE and western blot analysis showed high levels of
      expression of the 21 kDa and 31 kDa XYNB proteins in transgenic potato plants
      transformed by the binary vectors pBinXy and signal peptide contained pBinSPXy,
      respectively. The recombinant XYNB protein was present at up to 5% of total
      soluble leaf protein in the cytoplasm. In transgenic leaf and tuber extracts,
      xylanase activity was up to 87 micromol min(-1) g(-1) fresh leaf (9.7 micromol
      min(-1) mg(-1) total soluble protein). The xylanase was stable at 60 degrees C
      and 70 degrees C in buffers (pH 5.2) for 5 min. Furthermore, the xylanase
      enzymatic activity remained virtually unchanged over several generations of
      potato. These results demonstrate that the transgenic potato can be used to
      produce recombinant xylanase with high specific enzyme activity and can
      potentially be an alternative to present-day xylanase additives to animal feed.

PMID- 17206371
TI  - Transient co-expression of post-transcriptional gene silencing suppressors and
      beta-glucuronidase in harvested lettuce leaf tissue does not improve recombinant
      protein accumulation in planta.
AB  - Agrobacterium-mediated gene transfer was used to co-express three virus-derived
      post-transcriptional gene silencing (PTGS) suppressors, P19 from tomato bushy
      stunt virus and two species of helper component proteinase (HcPro) from tobacco
      etch virus (TEV) and turnip mosaic virus, with beta-glucuronidase (GUS) in
      harvested lettuce leaf tissue to investigate whether GUS accumulation increases
      in the presence of PTGS suppressors. Co-expression incubations were 3-5 days at 4
      and 22 degrees C. GUS activity and leaf viability were measured after incubation.
      Co-expression of PTGS suppressors did not elevate GUS expression levels. Under
      certain incubation conditions, co-expression of TEV HcPro significantly lowered
      transient GUS expression and was detrimental to leaf viability, suggesting that
      expression of PTGS silencers may have a negative effect on transient expression
      levels that outweighs any effects of PTGS suppression in harvested leaf tissues.

PMID- 17206372
TI  - Production of D-tagatose at high temperatures using immobilized Escherichia coli
      cells expressing L-arabinose isomerase from Thermotoga neapolitana.
AB  - Escherichia coli cells expressing L-arabinose isomerase from Thermotoga
      neapolitana (TNAI) were immobilized in calcium alginate beads. The resulting cell
      reactor (2.4 U, t (1/2) = 43 days at 70 degrees C) in a continuous recycling mode
      at 70 degrees C produced 49 and 38 g D-tagatose/l from 180 and 90 g D
      galactose/l, respectively, within 12 h.

PMID- 17206373
TI  - Improved procedure for separation and purification of Arthronema africanum
      phycobiliproteins.
AB  - A rapid, inexpensive and reliable procedure for separation and purification of C
      phycocyanin (C-PC) and allophycocyanin (APC) from Arthronema africanum based on a
      previously described rivanol-sulfate method for C-PC purification was developed.
      Exclusion of NaCl from the extraction buffer resulted in complete separation of
      APC and C-PC, two-fold reduction of rivanol treatments, and a higher yield and
      purity of C-PC. Pure C-PC (A(620)/A(280) of 4.52) and APC (A(652)/A(280) of 2.41)
      were obtained. The estimated molecular masses of the alpha and beta subunits were
      17 and 19 kDsmall a, Cyrillic for capital ES, Cyrillic-phycocyanin and 16 and 18
      kDsmall a, Cyrillic for APC, respectively. The overall C-PC recovery of 55% (w/w)
      from its content (100 mg) in the crude extract was 10-20% higher than so far
      reported. The procedure appears promising for scaling up and broader
      applications.

PMID- 17206374
TI  - A comparison of enzymatic phosphorylation and phosphatidylation of beta-L- and
      beta-D-nucleosides.
AB  - Enzymatic 5'-monophosphorylation and 5'-phosphatidylation of a number of beta-L-
      and beta-D-nucleosides was investigated. The first reaction, catalyzed by
      nucleoside phosphotransferase (NPT) from Erwinia herbicola, consisted of the
      transfer of the phosphate residue from p-nitrophenylphosphate (p-NPP) to the 5'
      hydroxyl group of nucleoside; the second was the phospholipase D (PLD)-catalyzed
      transphosphatidylation of L-alpha-lecithin with a series of beta-L- and beta-D
      nucleosides as the phosphatidyl acceptor resulted in the formation of the
      respective phospholipid-nucleoside conjugates. Some beta-L-nucleosides displayed
      similar or even higher substrate activity compared to the beta-D-enantiomers.

PMID- 17206375
TI  - Characterization of raffinose synthase from rice (Oryza sativa L. var.
      Nipponbare).
AB  - The putative raffinose synthase gene from rice was cloned and expressed in
      Escherichia coli. The enzyme displayed an optimum activity at 45 degrees C and pH
      7.0, and a sulfhydryl group was required for its activity. The enzyme was
      specific for galactinol and p-nitrophenyl-alpha-D-galactoside as galactosyl
      donors, and sucrose, lactose, 4-beta-galactobiose, N-acetyl-D-lactosamine,
      trehalose and lacto-N-biose were recognized as galactosyl acceptors.

PMID- 17206376
TI  - Biodegradation of crystal violet by Pseudomonas putida.
AB  - Crystal violet (CV), which has been extensively used as a biological stain and a
      commercial textile dye, is a recalcitrant molecule. A strain of Pseudomonas
      putida was isolated that effectively degraded CV: up to 80% of 60 microM CV as
      the sole carbon source, was degraded in liquid media within 1 week. Nine
      degradation products were isolated and identified. We propose that CV degradation
      occurs via a stepwise demethylation process to yield mono-, di-, tri-, tetra-,
      penta- and hexa-demethylated CV species.

PMID- 17206377
TI  - The G277S transferrin mutation does not affect iron absorption in iron deficient
      women.
AB  - BACKGROUND: Iron deficiency anaemia is one of the most important nutritional
      diseases, with high prevalence worldwide. The G277S transferrin mutation has been
      implicated as a risk factor for iron deficiency in menstruating women. However,
      the subject is controversial and there are no data concerning the possible
      influence of this polymorphism on iron absorption. AIM OF THE STUDY: To undertake
      a pilot study to investigate the effect of carrying the G277S transferrin
      mutation on non-haem iron absorption from a meal in young menstruating women
      compared to wild-type controls. METHODS: Menstruating women with low iron stores
      (serum ferritin < 30 microg/l) or who had suffered from iron deficiency anaemia
      or had a family history of anaemia were recruited (n = 162). Haematological
      parameters were analysed, including haemoglobin, ferritin, total-iron binding
      capacity and transferrin saturation. Non-haem iron absorption from a meal was
      measured in 25 non-anaemic women either with the G277S/G277G (n = 10) or the wild
      type G277G/G277G (n = 15) genotype. The incorporation of stable isotopes of iron
      into erythrocytes was used to measure absorption. RESULTS AND CONCLUSIONS: There
      were no significant differences in iron status indices or non-haem iron
      absorption between genotypes. However, G277S carriers did not show the usual
      inverse association between iron stores and non-haem iron absorption. Further
      studies should focus on the effects of a combination of polymorphisms in iron
      metabolism genes on iron absorption.

PMID- 17206378
TI  - High glucose promotes the production of collagen types I and III by cardiac
      fibroblasts through a pathway dependent on extracellular-signal-regulated kinase
      1/2.
AB  - Hyperglycemia promotes fibrosis by increasing collagen synthesis, a process
      involving mitogen activated protein kinases (MAPKs). Several studies of diabetic
      cardiomyopathy have demonstrated an accumulation of collagen, including collagen
      types I and III, in the myocardium, leading to interstitial fibrosis, which is
      related to left-ventricular diastolic dysfunction. However, the mechanisms of
      hyperglycemia-induced collagen production in cardiac fibroblasts are poorly
      defined. In the present study, neonatal rat cardiac fibroblasts treated with high
      glucose (25 mM) were assessed by real time PCR and enzyme linked immunosorbent
      assay (ELISA) showed an increase in both the mRNA and protein level of collagen
      types I and III. These effects were not due to changes in osmotic pressure.
      Extracellular signal regulated kinase 1/2 (ERK1/2) was activated by high glucose
      level (25 mM), and treatment with PD98059 to block ERK phosphorylation
      significantly inhibited the mRNA and protein expression of collagen types I and
      III. These results suggest that high glucose accelerates the synthesis of
      collagen types I and III, and an ERK1/2 cascade in cardiac fibroblasts play an
      essential role in the control of collagen deposition by high glucose.

PMID- 17206379
TI  - Osteogenic differentiation of adipose derived stem cells promoted by
      overexpression of osterix.
AB  - Adipose-derived stem cells (ASCs) are considered to be multipotent mesenchymal
      stem cells that are easily induced to differentiate into functional osteoblasts
      both in vitro and in vivo. Osterix (Osx) is a zinc finger-containing
      transcription factor of Sp gene family, which plays important roles in bone
      development and mineralization. In this study, we hypothesized that
      overexpression of Osx in murine ASCs would promote their osteogenic
      differentiation in vitro. A plasmid expressing Osx (pcDNA3.1-Osx) was constructed
      and applied to transfect monolayers of murine ASCs. Then expression of bone
      related genes, nodule formation, proliferation rate, and alkaline phosphatase
      activity were examined to evaluate the osteogenic potential of ASCs with pcDNA3.1
      Osx transfection. Results of RT-PCR and immunohistochemistry showed that pcDNA3.1
      Osx transfection enhanced the expression of bone matrix proteins, such as bone
      sialoprotein, osteocalcin, osteopontin, and Collagen type I in ASCs. At the same
      time, overexpression of Osx in ASCs enhanced alkaline phosphatase activity and
      capability to form mineralized nodules, while not inhibited their proliferation
      rate. These results indicated that pcDNA3.1-Osx transfection promoted the
      osteogenic differentiation of ASCs, while not affecting their proliferative
      ability. Since they can be easily isolated and genetically modified, ASCs are
      hopeful cell sources in the further application of hard tissue engineering.

PMID- 17206380
TI  - Protein kinase A phosphorylation of the multifunctional protein CAD antagonizes
      activation by the MAP kinase cascade.
AB  - The flux through the de novo pyrimidine biosynthetic pathway is controlled by the
      multifunctional protein CAD, which catalyzes the first three steps. The cell
      cycle dependent regulation of pyrimidine biosynthesis is a consequence of
      sequential phosphorylation of CAD Thr456 and Ser1406 by the MAP kinase and PKA
      cascades, respectively. Coordinated regulation of the pathway requires precise
      timing of the two phosphorylation events. These studies show that phosphorylation
      of purified CAD by PKA antagonizes MAP kinase phosphorylation, and vice versa.
      Similar results were observed in vivo. Forskolin activation of PKA in BHK-21
      cells resulted in a 8.5 fold increase in Ser1406 phosphorylation and severely
      curtailed the MAP kinase mediated phosphorylation of CAD Thr456. Moreover, the
      relative activity of MAP kinase and PKA was found to determine the extent of
      Thr456 phosphorylation. Transfectants expressing elevated levels of MAP kinase
      resulted in a 11-fold increase in Thr456 phosphorylation, whereas transfectants
      that overexpress PKA reduced Thr456 phosphorylation 5-fold. While phosphorylation
      of one site by one kinase may induce conformational changes that interfere with
      phosphorylation by the other, the observation that both MAP kinase and PKA form
      stable complexes with CAD suggest that the mutual antagonism is the result of
      steric interference by the bound kinases. The reciprocal antagonism of CAD
      phosphorylation by MAP kinase and PKA provides an elegant mechanism to coordinate
      the cell cycle-dependent regulation of pyrimidine biosynthesis ensuring that
      signals for up- and down-regulation of the pathway do not conflict.

PMID- 17206381
TI  - Antioxidant enzyme inhibitors enhance peroxynitrite-induced cell death in U937
      cells.
AB  - Peroxynitrite, a potent physiological inorganic toxin, is known to play a
      critical role in cellular oxidative damage. The protective role of antioxidant
      enzymes against peroxynitrite-induced oxidative damage in U937 cells was
      investigated in control and cells pre-treated with diethyldithiocarbamic acid,
      aminotriazole, and oxlalomalate, specific inhibitors of superoxide dismutase,
      catalase, and NADP(+)-dependent isocitrate dehydrogenase, respectively. Upon
      exposure to 1 mM 3-morpholinosydnomine N-ethylcarbamide (SIN-1), a generator of
      peroxynitrite through the reaction between nitric oxide and superoxide anion, to
      U937 cells, the viability was lower and the protein oxidation, lipid peroxidation
      and oxidative DNA damage reflected by an increase in 8-hydroxy-2'-deoxyguanosine,
      were higher in the inhibitor-treated cells as compared to the control cells. We
      also observed the significant increase in the endogenous production of reactive
      oxygen species, as measured by the oxidation of 2'7'-dichlorodihydrofluorescin as
      well as the significant decrease in the intracellular GSH level in the inhibitor
      treated U937 cells upon exposure to SIN-1. These results suggest that antioxidant
      enzymes play an important role in cellular defense against peroxynitrite-induced
      cell death.

PMID- 17206382
TI  - Glutathione and glutathione-linked enzymes in normal human aortic smooth muscle
      cells: chemical inducibility and protection against reactive oxygen and nitrogen
      species-induced injury.
AB  - Substantial evidence suggests a crucial role for glutathione (GSH) and GSH-linked
      enzymes in protecting against oxidative vascular disorders. However, studies on
      the chemical inducibility of these antioxidant defenses and their protective
      effects on oxidant injury in normal human vascular cells are currently lacking.
      Accordingly, this study was undertaken to investigate the inducibility of GSH,
      glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S
      transferase (GST) by the chemoprotective agent, 3H-1,2-dithiole-3-thione (D3T) in
      cultured normal human aortic smooth muscle cells (HASMCs). HASMCs expressed
      measurable levels/activities of GSH, GR, GPx, and GST. Incubation of HASMCs with
      low micromolar concentrations of D3T resulted in a marked elevation in total
      cellular GSH content and GR activity. The protein and mRNA expression of gamma
      glutamylcysteine ligase (GCL) and GR were also upregulated by D3T. In addition,
      D3T caused significant increases in mitochondrial GSH content and GR activity. In
      contrast, neither cellular GPx nor GST activity was altered after D3T treatment.
      Pretreatment of HASMCs with D3T afforded remarkable protection against reactive
      oxygen and nitrogen species (ROS/RNS)-mediated cell injury. Depletion of cellular
      GSH by pretreatment with buthionine sulfoximine (BSO), an inhibitor of GSH
      biosynthesis led to marked potentiation of the ROS/RNS-induced cell injury.
      Moreover, co-treatment of HASMCs with BSO was found to completely abolish the D3T
      mediated GSH elevation, and remarkably reverse D3T cytoprotection against the
      ROS/RNS-elicited injury. Taken together, this study demonstrates that both
      GSH/GCL and GR in normal HASMCs are inducible by D3T, and that upregulation of
      GSH biosynthesis appears to be the predominant mechanism underlying D3T-mediated
      cytoprotection against ROS/RNS-elicited injury to human vascular smooth muscle
      cells.

PMID- 17206384
TI  - Iron acquisition in the dental pathogen Actinobacillus actinomycetemcomitans:
      what does it use as a source and how does it get this essential metal?
AB  - Actinobacillus actinomycetemcomitans requires iron to grow under limiting
      conditions imposed by synthetic and natural chelators. Although none of the
      strains tested used hemoglobin, lactoferrin or transferrin, all of them used
      FeCl3 and hemin as iron sources under chelated conditions. Dot-blot binding
      assays showed that all strains bind lactoferrin, hemoglobin, and hemin but not
      transferrin. When compared with smooth strains, the rough isolates showed higher
      hemin binding activity, which was sensitive to proteinase K treatment. A.
      actinomycetemcomitans harbors the Fur-regulated afeABCD locus coding for iron
      acquisition in isogenic and non-isogenic cell backgrounds. The genome of this
      oral pathogen also harbors several other predicted iron uptake genes including
      the hitABC locus, which restored iron acquisition in the E. coli 1017 ent mutant.
      However, the disruption of this locus in the parental strain did not affect iron
      acquisition as drastically as the inactivation of AfeABCD, suggesting that the
      latter system could be more involved in iron transport than the HitABC system.
      The genome of this oral pathogen also harbors an active copy of the exbBexbDtonB
      operon, which could provide the energy needed for hemin acquisition. However,
      inactivation of each coding region of this operon did not affect the hemin and
      iron acquisition phenotypes of isogenic derivatives. This observation suggests
      that the function of these proteins could be replaced by those coded for by tolQ,
      tolR and tolA as it was described for other bacterial transport systems.
      Interruption of a hasR homolog, an actively transcribed gene that is predicted to
      code for an outer membrane hemophore receptor protein, did not affect the ability
      of an isogenic derivative to bind and use hemin under chelated conditions. This
      result also indicates that A. actinomycetemcomitans could produce more than one
      outer membrane hemin receptor as it was described in other human pathogens. All
      strains tested formed biofilms on plastic under iron-rich and iron-chelated
      conditions. However, smooth strains attached poorly and formed weaker biofilms
      when compared with rough isolates. The incubation of rough cells in the presence
      of FeCl3 or hemin resulted in an increased number of smaller aggregates and
      microcolonies as compared to the fewer but larger aggregates formed when cells
      were grown in the presence of dipyridyl.

PMID- 17206383
TI  - Plasminogen and angiostatin interact with heat shock proteins.
AB  - Previous studies from this laboratory have demonstrated that plasminogen and
      angiostatin bind to endothelial cell (EC) surface-associated actin via their
      kringles in a specific manner. Heat shock proteins (hsps) like hsp 27 are
      constitutively expressed by vascular ECs and regulate actin polymerization, cell
      growth, and migration. Since many hsps have also been found to be highly abundant
      on cell surfaces and there is evidence that bacterial surface hsps may interact
      with human plasminogen, the purpose of this study was to determine whether human
      plasminogen and angiostatin would interact with human hsps. ELISAs were developed
      in our laboratory to assess these interactions. It was observed that plasminogen
      bound to hsps 27, 60, and 70. In all cases, binding was inhibited (85-90%) by
      excess (50 mM) lysine indicating kringle involvement. Angiostatin predominantly
      bound to hsp 27 and to hsp 70 in a concentration- and kringle-dependent manner.
      As observed previously for actin, there was concentration-dependent inhibition of
      angiostatin's interaction with hsp 27 by plasminogen. In addition, 30-fold molar
      excess actin inhibited (up to 50%), the interaction of plasminogen with all hsps.
      However, 30-fold molar excess actin could only inhibit the interaction of
      angiostatin with hsp 27 by 15-20%. Collectively, these data indicate that (i)
      while plasminogen interacts specifically with hsp 27, 60, and 70, angiostatin
      interacts predominantly with hsp 27 and to some extent with hsp 70; (ii)
      plasminogen only partially displaces angiostatin's binding to hsp 27 and (iii)
      actin only partially displaces plasminogen/angiostatin binding to hsps. It is
      conceivable therefore that surface-associated hsps could mediate the binding of
      these ligands to cells like ECs.

PMID- 17206385
TI  - Heme, an iron supply for vibrios pathogenic for fish.
AB  - One of the main mechanisms present in gram-negative bacterial pathogens to obtain
      iron is the utilization of free heme or heme proteins from the host tissues.
      Vibrio anguillarum, the etiological agent of vibriosis in fish, and
      Photobacterium damselae subsp. piscicida, the causative agent of fish
      pasteurellosis, can acquire iron from free heme or heme-containing proteins
      present in the host tissues by a siderophore-independent mechanism. Similarly to
      other animal and human pathogens, the general mechanism for heme uptake in these
      two species consists in the presence of an outer membrane receptor that transport
      the heme molecule into the periplasm via a TonB-dependent process, and additional
      proteins that complete the transport of heme from the periplasm into the cell
      cytoplasm. Expression of heme uptake genes is iron-regulated at the
      transcriptional level by the repressor protein Fur. The heme uptake mechanisms
      are believed to contribute to virulence for fish. The existence of variability in
      the distribution of heme transport genes among strains suggests that gene
      inactivation and/or horizontal transfer might play a significant role in
      generating intraspecific genetic diversity.

PMID- 17206386
TI  - Roles of the Yfe and Feo transporters of Yersinia pestis in iron uptake and
      intracellular growth.
AB  - In Yersinia pestis, the Yfe and Feo systems likely function to transport ferrous
      iron. Both FeoA and FeoB are essential for iron acquisition activity while FeoC
      is not. Mutations in yfe and feo had an additive effect on microaerophilic growth
      under iron-chelating conditions. Y. pestis cells lacking the Ybt siderophore
      dependent system, the Yfe or the Feo system grow normally in J774A.1 cells.
      However, a double yfeAB feoB mutant was no longer able to grow in this murine
      macrophage cell line. This growth defect likely resulted from iron and not
      manganese deprivation since a yfeAB mntH mutant grew normally in J774A.1 cells.
      These results suggest that the Yfe and Feo systems are somewhat redundant ferrous
      iron transporters capable of iron acquisition during intracellular growth of the
      plague bacterium.

PMID- 17206387
TI  - Spontaneous hemothorax in neurofibromatosis treated with percutaneous
      embolization.
AB  - We evaluated the effectiveness of transcatheter arterial coil embolization
      therapy for the treatment of spontaneous hemothorax followed by aneurysm rupture
      in neurofibromatosis patients. Three patients were treated for massive hemothorax
      caused by arterial lesions associated with neurofibromatosis. Bleeding episodes
      were secondary to ascending cervical artery aneurysm and dissection of vertebral
      artery in 1 patient, and intercostal artery aneurysm with or without
      arteriovenous fistula in 2 patients. Patients were treated by transarterial coil
      embolization combined with chest drainage. In 1 patient, the ruptured ascending
      cervical artery aneurysm was well embolized but, shortly after the embolization,
      fatal hemorrhage induced by dissection of the vertebral artery occurred and the
      patient died. In the other 2 patients, the ruptured intercostal artery aneurysm
      was well embolized and they were successfully treated and discharged.
      Transcatheter arterial coil embolization therapy is an effective method for the
      treatment of spontaneous hemothorax followed by aneurysm rupture in
      neurofibromatosis patients.

PMID- 17206388
TI  - Preoperative embolization of a tumor-bearing horseshoe kidney via both channels
      of a concomitant aortic dissection.
AB  - Renal cell carcinoma arising in a horseshoe kidney is a rare entity. Preoperative
      tumor embolization can be performed to prevent massive bleeding complications
      during organ-preserving surgery. We report the first case of a patient with a
      tumor-bearing horseshoe-kidney in whom the preoperative embolization, already
      complex because of the abnormal vascular supply, was additionally complicated by
      an aortic dissection. An aberrant, horseshoe-kidney-supplying artery originated
      from the false dissection channel of the aorta, and thus had to be catheterized
      separately while the other tumor-supplying vessels could be reached via the true
      aortic lumen. After devascularization of the tumor, organ-preserving surgery was
      performed without bleeding complications.

PMID- 17206389
TI  - Lipid-altering therapies and the progression of atherosclerotic disease.
AB  - Lipids play a key role in the progression of atherosclerosis, and lipid-lowering
      therapies have been studied for 30 years in coronary disease. Measurement of the
      progression of atherosclerosis through carotid intima-media thickness, coronary
      mean lumen diameter, and, mostly recently, intravascular ultrasound is generally
      accepted. This article reviews the role of lipid-lowering therapies in changing
      the rate of atherosclerosis progression in the coronary and carotid circulations.
      Statins are the primary therapy used to reduce atherosclerosis and cardiovascular
      events, including strokes and transient ischemic attacks, and have benefits in
      reducing events in patients undergoing carotid endarterectomy. In contrast, data
      for other agents, including fibrates and nicotinic acid, in reducing the
      progression of atherosclerosis are less extensive and not as well known. There is
      increasing interest in optimizing the whole lipid profile, as this might deliver
      extra benefits over and above statin therapy alone. Initial proof of this concept
      has recently come from studies that measured the progression of atherosclerosis
      and showed that adding nicotinic acid to statin therapy and, more directly,
      infusion of high-density lipoprotein-like particles reduced progression and
      indeed might induce regression of the disease. It is likely that the management
      of significant carotid stenosis will become ever more drug focused and will be
      customized to the lipid profile of each patient with intervention reserved only
      for late-stage symptomatic disease.

PMID- 17206390
TI  - Endovascular treatment of descending thoracic aortic aneurysms with the EndoFit
      stent-graft.
AB  - OBJECTIVE: To evaluate the mid-term feasibility, efficacy, and durability of
      descending thoracic aortic aneurysm (DTAA) exclusion using the EndoFit device
      (LeMaitre Vascular). METHODS: Twenty-three (23) men (mean age 66 years) with a
      DTAA were admitted to our department for endovascular repair (21 were ASA III+
      and 2 refused open repair) from January 2003 to July 2005. RESULTS: Complete
      aneurysm exclusion was feasible in all subjects (100% technical success). The
      median follow-up was 18 months (range 8-40 months). A single stent-graft was used
      in 6 cases. The deployment of a second stent-graft was required in the remaining
      17 patients. All endografts were attached proximally, beyond the left subclavian
      artery, leaving the aortic arch branches intact. No procedure-related deaths have
      occurred. A distal type I endoleak was detected in 2 cases on the 1 month follow
      up CT scan, and was repaired with reintervention and deployment of an extension
      graft. A nonfatal acute myocardial infarction occurred in 1 patient in the sixth
      postoperative month. Graft migration, graft infection, paraplegia, cerebral or
      distal embolization, renal impairment or any other major complications were not
      observed. CONCLUSION: The treatment of DTAAs using the EndoFit stent-graft is
      technically feasible. Mid-term results in this series are promising.

PMID- 17206391
TI  - Percutaneous placement of peritoneal port-catheter in patients with malignant
      ascites.
AB  - We report our experience with a radiologically placed peritoneal port-catheter in
      palliation of malignant ascites. Port-catheters were successfully placed under
      ultrasonographic and fluoroscopic guidance in seven patients (five women, two
      men) who had symptomatic malignant ascites. The long-term primary patency rate
      was 100%. The mean duration of catheter function was 148 days. Seven patients had
      a total of 1040 port-days. Two patients received intraperitoneal chemotherapy via
      the port-catheter. There were no procedure-related mortality and major
      complications. Minor complications such as ascitic fluid leakage from the
      peritoneal entry site, migration of the catheter tip to the right upper quadrant,
      and reversal of the port reservoir occurred in four patients. None of these
      complications affected the drainage and required port explantation. In patients
      with symptomatic malignant ascites, a peritoneal port-catheter can provide
      palliation and eliminate multiple hospital visits for repeated paracentesis with
      high patency and low complication rates.

PMID- 17206392
TI  - Transcatheter embolization of a renal artery aneurysm using ethylene vinyl
      alcohol copolymer.
AB  - Our aim was to treat a clinically silent renal artery aneurysm. The patient was a
      76-year-old man with elevated prostate-specific antigen and prostate biopsies
      with a grade II-III adenocarcinoma who was incidentally found to have an aneurysm
      in his right renal artery. We performed a successful transcatheter embolization
      of the aneurysm using ethylene vinyl alcohol copolymer (Onyx). To avoid migration
      of the liquid material into the parent artery, a balloon was inflated in the
      orifice of the neck of the aneurysm while the liquid was injected. Five-month
      follow-up computed tomography (CT) imaging confirmed total occlusion of the
      aneurysm.

PMID- 17206393
TI  - Late intrahepatic hematoma complicating transjugular intrahepatic portosystemic
      shunt for Budd-Chiari syndrome.
AB  - Late intrahepatic hematoma is a rare complication of the transjugular
      intrahepatic portosystemic shunt (TIPS) procedure. We describe a patient with
      Budd-Chiari syndrome (BCS) who presented with a large intrahepatic hematoma 13
      days after TIPS. Review of the literature revealed only 2 previous cases, both
      occurring in patients with BCS and presenting after a similar time interval. This
      potentially serious complication appears to be specific for TIPS in BCS.

PMID- 17206394
TI  - Isolation of Pseudomonas aeruginosa from open ocean and comparison with
      freshwater, clinical, and animal isolates.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen responsible for morbidity and
      mortality in humans, animals, and plants. This bacterium has been regarded to be
      widely present in terrestrial and freshwater environments, but not in open ocean
      environments. Our purpose was to clarify its presence in open ocean, and their
      genotypic and physiological characteristics were compared with those of isolates
      from clinical, animal, and freshwater sources. Water samples were collected from
      freshwater, bays, and offshore environments in Japan. Sixty-two isolates,
      including 26 from the open ocean, were identified as P. aeruginosa by phenotypic
      characteristics and the BD Phoenix System. Pulsed-field gel electrophoresis
      (PFGE) was performed on all strains, together with 21 clinical and 8 animal
      strains. The results showed that open ocean strains are composed of a few
      genotypes, which are separated from other strains. Although some clinical
      isolates made a cluster, other strains tended to mix together. Different
      antibiotypes were observed among marine isolates that had similar PFGE and
      serotyping patterns. Some were multidrug-resistant. Laboratory-based microcosm
      study were carried out to see the responses of P. aeruginosa toward increased
      NaCl concentrations in deionized water (DW). Marine strains showed better
      survival with the increase, whereas river and clinical strains were suppressed by
      the increase. These findings illustrate the potential significance of open ocean
      as a possible reservoir of P. aeruginosa, and there may be clones unique to this
      environment. To our knowledge, this is the first report on the presence and
      characterization of P. aeruginosa in the open ocean.

PMID- 17206395
TI  - Oxidant/antioxidant status in men with Behcet's disease.
AB  - Behcet's disease (BD) is a chronic, progressive disorder that affects many
      systems of the body including the eye. The aim of this study was to assess
      whether the increase in oxidative stress in the affected tissues is reflected by
      lipid peroxidation and to check for alterations in antioxidants and antioxidant
      enzyme activities in patients with BD. Erythrocyte antioxidant potential (AOP),
      glutathione (GSH) and GSH-dependent enzymes (glutathione peroxidase (GSH-Px),
      glutathione reductase (GRD) and glutathione-S-transferase (GST), catalase (CAT),
      Cu-Zn superoxide dismutase (Cu-Zn SOD) activities, malondialdehyde (MDA) and some
      trace elements (zinc, Zn; copper, Cu; manganese, Mn) levels in men with BD.
      Erythrocyte CAT, GSH-Px activities, MDA, GSH, AOP and serum Zn values were
      significantly lower in patients with BD than in the control group. However,
      erythrocyte Cu-Zn SOD, GRD activities, erythrocyte sedimentation rate (ESR),
      serum C-reactive protein (CRP) and Cu values were significantly higher in
      patients with BD than in the control group, but GST activity and serum Mn values
      were unchanged. In conclusion, our results confirm the presence of oxidative
      stress in patients with BD and suggest that the severity of BD may arise from
      impaired antioxidant mechanisms. Therapy with antioxidants may lead to the
      increase in the antioxidant defense system and thus improvement in clinical
      symptoms.

PMID- 17206396
TI  - Serum-soluble selectin levels in patients with Behcet's disease.
AB  - Soluble forms of selectins may play a regulatory role in inflammatory responses.
      The aim of this study was to examine the levels of serum-soluble (s) selectins in
      Behcet's disease (BD) patients and to evaluate the associations of these
      molecules to disease activity, clinical findings, and drugs taken for BD, mainly
      colchicine. Serum sE-, sL-, and sP-selectins levels were measured by sandwich
      enzyme-linked immunosorbent assay in 28 BD patients and 22 healthy subjects. The
      BD patients were classified according to the disease activity, clinical findings,
      and therapy. Ten patients were newly diagnosed and were not taking any therapy.
      Remainder were on colchicine (n = 18) and immunosuppressive drugs (n = 5). In BD
      patients, the levels of sL- and sP-selectins were significantly lower than those
      of healthy controls, but sE-selectin level was similar to that of the controls.
      The patients on the therapy had significantly lower levels of sE- and sL
      selectins and insignificantly lower level of sP-selectin than the patients not
      receiving therapy. The BD patients with active disease had significantly higher
      levels of sE-, sL-, and sP-selectins compared with the patients with inactive
      disease. There were no significant differences in the levels of selectins between
      the treated active patients and inactive patients. However, the untreated
      patients with active disease had significantly higher selectin levels than the
      inactive patients. There were no significant differences in all selectin levels
      between the patients with or without vascular involvement. Serum sL-selectin was
      found to be significantly higher in patients with erythema nodosum. In
      conclusion, our findings suggest that the levels of soluble selectin molecules in
      BD patients seem to be modified by the drugs taken for BD. The colchicine therapy
      is associated with lower selectin levels.

PMID- 17206397
TI  - Bone biopsy and densitometry findings in a child with Camurati-Engelmann disease.
AB  - Progressive diaphyseal dysplasia (MIM 131300), also known as Camurati-Engelmann
      disease (CED), is a rare autosomal dominant craniotubular dysplasia caused by
      mutations in the transforming growth factor beta1 (TGF-beta1) gene. Radiographs
      of the long bones of a 9-year-old boy presenting with waddling gait, muscular
      weakness, underweight, and severe skeletal pain showed symmetric diaphyseal
      cortical thickening pathognomonic for CED. The diagnosis was verified by
      detecting a mutation in exon 4 of the TGF-beta1 gene. Full body bone mineral
      densitometry studies performed before treatment with prednisolone were indicative
      for osteoporosis (Z-scores for the lumbar spine and femoral neck -2.3 and -3.2,
      respectively). A transiliac bone biopsy showed markedly reduced trabecular bone
      volume. Oral prednisolone was initiated, and subsequently, pamidronate infusions
      were commenced in an attempt to prevent progression of osteoporosis. To our
      knowledge, this is the first time bone biopsy and bone mineral densitometry
      studies have been performed and bisphosphonate treatment evaluated in a child
      with CED.

PMID- 17206398
TI  - Rheumatoid arthritis is linked to Proteus--the evidence.
AB  - Rheumatoid arthritis (RA) is a chronic inflammatory arthritic and potentially
      disabling condition, mainly affecting women of middle age and having
      characteristic clinical features. Various microbial agents were implicated in the
      causation of RA. Extensive literature based on the results of various genetic,
      microbiological, molecular, and immunological studies carried out by independent
      research groups supports the role of Proteus mirabilis bacteria in the
      etiopathogenesis of RA. New diagnostic markers and criteria and the use of a
      novel therapeutic protocol in the form of antibiotic and dietary measures are
      suggested to be used together with current treatments in the management of RA.
      Prospective longitudinal studies with the use of antimicrobial measures in
      patients with RA are required to establish the therapeutic benefit of this
      microbe-disease association.

PMID- 17206399
TI  - High bone mineral density in pycnodysostotic patients with a novel mutation in
      the propeptide of cathepsin K.
AB  - INTRODUCTION: Pycnodysostosis is typically associated with short stature,
      multiple fractures without adequate trauma and high bone density on x-ray. The
      increased bone density is due to a genetic defect of cathepsin K, leading to
      dysfunctional osteoclastic bone resorption and bone remodeling. We wanted to know
      how this defect influences the trabecular and cortical volumetric bone mineral
      density of long bones as measured quantitatively by pQCT. METHODS: Three siblings
      of a consanguineous family were admitted to our hospital because of multiple
      fractures. Pycnodysostosis was diagnosed based on the clinical presentation with
      the characteristic dense appearance of their bones on x-ray. The distal and
      proximal radius of the patients and of control subjects was scanned using a
      Stratec XCT-2000 pQCT scanner and data were processed using the software provided
      by the manufacturer. Genomic DNA was extracted from blood samples of all three
      patients and their parents. The coding exons of the cathepsin K gene (CTSK) were
      amplified and sequenced. RESULTS: The patients displayed the typical features of
      pycnodysostosis: Short stature, delay of closure of the fontanelles, hypoplasia
      of the maxilla, spondylolysis of the lumbar spine, stubby hands and feet and a
      history of multiple fractures. Volumetric bone density was much higher in
      pycnodysostotic bone than in the control bones 686 +/- 28 mg/cm(3) in patients
      vs. 290 +/- 6 mg/cm(3) in controls; p = 0.001), especially in the trabecular
      compartment (733 +/- 26 mg/cm(3) in patients vs. 195 +/- 8 mg/cm(3) in controls;
      p < 0.001), but also in the cortical bone (1108 +/- 22 in patients vs. 1020 +/-
      17 in controls; p < 0.01). In contrast to this finding, the patients displayed an
      elevation of alkaline phosphatase in the serum and free deoxypyridinoline
      crosslinks (DPD) in the urine, suggesting osteomalacia. Sequencing of the
      cathepsin K gene revealed homozygosity for a novel missense mutation in all three
      patients predicting the amino acid exchange from arginine to tryptophan at
      position 46 (R46W). CONCLUSION: We present here for the first time quantitative
      data on the mineral density of bones of pycnodysostotic patients with a novel
      mutation in the propeptide of cathepsin K. The elevated bone mineral density in
      the cortex and the changes in the serum markers suggest an effect of cathepsin K
      not only on bone volume, but also on bone mineralization. This might in part
      explain the increased susceptibility to fractures of patients with
      pycnodysostosis.

PMID- 17206400
TI  - Fracture risk and antiresorptive medication use in older women in the USA.
AB  - Risk of fragility fractures in older women appears to be under-recognized and
      under treated. Analysis of a national sample of older US women reveals that over
      5 million are at high risk of fracture; only one third of these report being told
      they have osteoporosis and one quarter are receiving appropriate treatment.
      INTRODUCTION: Substantial numbers of older women in the United States suffer
      fragility fractures each year. Although risk for these fractures can be readily
      identified from clinical characteristics, many women may not be receiving
      treatments demonstrated to reduce risk. Our objective was to estimate the extent
      of fracture risk among older white US women and assess patterns of use of
      pharmacologic agents in response to that risk. METHODS: Cross-sectional data from
      the National Health and Nutrition Examination Survey (NHANES) for 1999-2000 and
      2001-2002 were combined to enumerate risk factors for fracture and use of
      antiresorptive prescription medications for all white women 65 years of age and
      older. The FRACTURE Index (FI), developed from the Study of Osteoporotic
      Fractures (SOF), which combines subjects' characteristics to estimate five-year
      fracture risk, was applied to these national data. RESULTS: Of more than 15
      million US women in this age group almost 40% have one risk factor in addition to
      age that predisposes to fracture; 20% have two or more. More than 5 million women
      are in the highest category of FI risk; 26% of these will have a nonvertebral
      fracture and 10% will have a vertebral fracture in the next five years.
      Antiresorptive medications are being taken by less than 50% of women in most risk
      categories when all antiresorptives, including estrogen replacement, are
      included; only 17% of older women who have sustained a prior fracture and 13% in
      the highest category of FI risk are receiving agents specifically intended to
      reduce bone loss. CONCLUSIONS: Millions of older US women are at high risk for
      fragility fractures. Levels of treatment with antiresorptive medications are low
      and are not commensurate with fracture risk.

PMID- 17206401
TI  - Comparison of the effects of bilateral posterior dynamic and rigid fixation
      devices on the loads in the lumbar spine: a finite element analysis.
AB  - A bilateral dynamic stabilization device is assumed to alter favorable the
      movement and load transmission of a spinal segment without the intention of
      fusion of that segment. Little is known about the effect of a posterior dynamic
      fixation device on the mechanical behavior of the lumbar spine. Muscle forces
      were disregarded in the few biomechanical studies published. The aim of this
      study was to determine how the spinal loads are affected by a bilateral posterior
      dynamic implant compared to a rigid fixator which does not claim to maintain
      mobility. A paired monosegmental posterior dynamic implant was inserted at level
      L3/L4 in a validated finite element model of the lumbar spine. Both a healthy and
      a slightly degenerated disc were assumed at implant level. Distraction of the
      bridged segment was also simulated. For comparison, a monosegmental rigid
      fixation device as well as the effect of implant stiffness on intersegmental
      rotation were studied. The model was loaded with the upper body weight and muscle
      forces to simulate the four loading cases standing, 30 degrees flexion, 20
      degrees extension, and 10 degrees axial rotation. Intersegmental rotations,
      intradiscal pressure and facet joint forces were calculated at implant level and
      at the adjacent level above the implant. Implant forces were also determined.
      Compared to an intact spine, a dynamic implant reduces intersegmental rotation at
      implant level, decreases intradiscal pressure in a healthy disc for extension and
      standing, and decreases facet joint forces at implant level. With a rigid
      implant, these effects are more pronounced. With a slightly degenerated disc
      intersegmental rotation at implant level is mildly increased for extension and
      axial rotation and intradiscal pressure is strongly reduced for extension. After
      distraction, intradiscal pressure values are markedly reduced only for the rigid
      implant. At the adjacent level L2/L3, a posterior implant has only a minor effect
      on intradiscal pressure. However, it increases facet joint forces at this level
      for axial rotation and extension. Posterior implants are mostly loaded in
      compression. Forces in the implant are generally higher in a rigid fixator than
      in a dynamic implant. Distraction strongly increases both axial and shear forces
      in the implant. A stiffness of the implant greater than 1,000 N/mm has only a
      minor effect on intersegmental rotation. The mechanical effects of a dynamic
      implant are similar to those of a rigid fixation device, except after
      distraction, when intradiscal pressure is considerably lower for rigid than for
      dynamic implants. Thus, the results of this study demonstrate that a dynamic
      implant does not necessarily reduce axial spinal loads compared to an un
      instrumented spine.

PMID- 17206402
TI  - Ericksonian hypnosis in tinnitus therapy: effects of a 28-day inpatient
      multimodal treatment concept measured by Tinnitus-Questionnaire and Health Survey
      SF-36.
AB  - For the first time, the therapeutic effects on subacute and chronic tinnitus of
      an inpatient multimodal treatment concept based on principles of Ericksonian
      hypnosis (EH) were examined by standardized criteria of the Tinnitus
      Questionnaire (TQ) and Health Survey (SF-36) within a controlled prospective,
      longitudinal study. A total of 393 patients were treated within an inpatient
      closed-group 28-day-setting based on a resource-oriented, hypnotherapeutic
      concept. The severity of tinnitus was assessed by TQ at times of admission,
      discharge and also at a 6- and 12-month follow-up. Health-related quality of life
      was evaluated before and after therapy using the SF-36. After therapy, a decrease
      in TQ score was seen in 90.5% of the patients with subacute tinnitus and in 88,3%
      of those with chronic tinnitus. Assessment of the TQ score at the end of therapy
      revealed highly significant improvements of 15.9/14.1 points in mean. Effect
      sizes in the treatment groups (0.94/0.80) were superior to those in the waiting
      list controls (0.14/0.23). The TQ score remained stable in the follow-up
      controls. Significant improvement in health-related quality of life has been
      observed within the treatment groups depending on initial level of tinnitus
      serverity I-IV according to TQ. Using a multimodal treatment concept with
      emphasis on resource-activating approaches of EH the annoyance of tinnitus can be
      significantly reduced while health-related quality of life is enhanced within a
      comparatively short treatment period of 28 days.

PMID- 17206404
TI  - Modeling the interaction of fipronil-related non-competitive antagonists with the
      GABA beta3-receptor.
AB  - A three-dimensional model of the beta3-homopentamer of the gamma-aminobutyric
      acid (GABA) receptor/chloride ionophore complex was developed by homology
      modeling using the cyro-electron microscopy structure of nicotinic acetylcholine
      as a template. Interactions between the beta3-homopentamer and two classes of
      fipronil-related non-competitive antagonists were investigated using docking
      studies. The phenyl groups of these compounds were stabilized by strong
      hydrophobic and hydrophilic interactions with the rings formed by Thr256 and
      Ala252. Leu253 and Ile255 were involved mainly in hydrophobic contact with the
      pyrazole moiety. Different substitution at positions 15, 16 and 17 of the
      pyrazole ring of fipronil resulted in weakening of the hydrogen bonds and
      hydrophobic interactions between the beta3-receptor and fipronil-related
      heterocyclic compounds, which maybe the principal cause of the decreased
      affinities reported in vitro. Moreover, a good correlation between total binding
      energies calculated by AutoDock and experimentally determined IC(50) values
      proved our models to be reasonable in predicting the interaction mode of the
      antagonist with the GABA beta3-receptor.

PMID- 17206403
TI  - Paraneoplastic syndromes in patients with primary head and neck cancer.
AB  - Paraneoplastic syndromes represent the clinical manifestations of the indirect
      and remote effects produced by tumor metabolites or other products. The clinical
      spectrum of the various paraneoplastic syndromes related to primary malignancies
      of the head and neck region is presented. A review of the literature on
      paraneoplastic syndromes in patients with primary head and neck cancer was
      carried out. Paraneoplastic syndromes related to primary malignancies of the head
      and neck region can be categorized as: endocrine, cutaneous or dermatologic,
      hematologic, neurologic, osteoarticular or rheumatologic, ocular syndromes.
      Sometimes, paraneoplastic syndromes can be more serious than the consequences of
      the primary tumor itself and can precede, follow or be concurrent to the
      diagnosis of a malignancy; moreover, they can dominate the clinical picture and
      thus lead to errors with respect to the origin and type of the primary tumor.
      Physicians who deal with cancer-associated syndromes should be able to
      differentiate the paraneoplastic syndromes from the benign disorders that mimic
      them. Patients with a suspected paraneoplastic disorder should undergo a complete
      panel of laboratory studies, in addition to imaging studies and endoscopy.
      Identification of paraneoplastic syndromes allow the clinician to make an early
      diagnosis and to provide adequate treatment of tumors, with a favorable oncologic
      outcome and improved life expectancy for the patient. These syndromes can follow
      the clinical course of the tumor and thus be useful for monitoring its evolution.

PMID- 17206405
TI  - Meconium pseudocyst secondary to ileal atresia complicated by volvulus: antenatal
      MR demonstration.
AB  - We report a case of meconium pseudocyst evaluated by prenatal MR imaging. The
      unusual features were its huge size, the absence of meconium peritonitis, and its
      development late in fetal life. The case also demonstrates a possible diagnostic
      pitfall since it suggests that rapid deterioration of a mechanically compensated
      bowel obstruction may occur, potentially occurring only after an MRI study has
      been performed.

PMID- 17206406
TI  - Insect sodium channels and insecticide resistance.
AB  - Voltage-gated sodium channels are essential for the generation and propagation of
      action potentials (i.e., electrical impulses) in excitable cells. Although most
      of our knowledge about sodium channels is derived from decades of studies of
      mammalian isoforms, research on insect sodium channels is revealing both common
      and unique aspects of sodium channel biology. In particular, our understanding of
      the molecular dynamics and pharmacology of insect sodium channels has advanced
      greatly in recent years, thanks to successful functional expression of insect
      sodium channels in Xenopus oocytes and intensive efforts to elucidate the
      molecular basis of insect resistance to insecticides that target sodium channels.
      In this review, I discuss recent literature on insect sodium channels with
      emphases on the prominent role of alternative splicing and RNA editing in the
      generation of functionally diverse sodium channels in insects and the current
      understanding of the interactions between insect sodium channels and
      insecticides.

PMID- 17206407
TI  - On the theory of reactive mixtures for modeling biological growth.
AB  - Mixture theory, which can combine continuum theories for the motion and
      deformation of solids and fluids with general principles of chemistry, is well
      suited for modeling the complex responses of biological tissues, including tissue
      growth and remodeling, tissue engineering, mechanobiology of cells and a variety
      of other active processes. A comprehensive presentation of the equations of
      reactive mixtures of charged solid and fluid constituents is lacking in the
      biomechanics literature. This study provides the conservation laws and entropy
      inequality, as well as interface jump conditions, for reactive mixtures
      consisting of a constrained solid mixture and multiple fluid constituents. The
      constituents are intrinsically incompressible and may carry an electrical charge.
      The interface jump condition on the mass flux of individual constituents is shown
      to define a surface growth equation, which predicts deposition or removal of
      material points from the solid matrix, complementing the description of volume
      growth described by the conservation of mass. A formulation is proposed for the
      reference configuration of a body whose material point set varies with time.
      State variables are defined which can account for solid matrix volume growth and
      remodeling. Constitutive constraints are provided on the stresses and momentum
      supplies of the various constituents, as well as the interface jump conditions
      for the electrochemical potential of the fluids. Simplifications appropriate for
      biological tissues are also proposed, which help reduce the governing equations
      into a more practical format. It is shown that explicit mechanisms of growth
      induced residual stresses can be predicted in this framework.

PMID- 17206409
TI  - Determination of polybrominated diphenyl ethers in environmental standard
      reference materials.
AB  - Standard reference materials (SRMs) are valuable tools in developing and
      validating analytical methods to improve quality assurance standards. The
      National Institute of Standards and Technology (NIST) has a long history of
      providing environmental SRMs with certified concentrations of organic and
      inorganic contaminants. Here we report on new certified and reference
      concentrations for 27 polybrominated diphenyl ether (PBDE) congeners in seven
      different SRMs: cod-liver oil, whale blubber, fish tissue (two materials), mussel
      tissue and sediment (two materials). PBDEs were measured in these SRMs, with the
      lowest concentrations measured in mussel tissue (SRM 1974b) and the highest in
      sediment collected from the New York/New Jersey Waterway (SRM 1944). Comparing
      the relative PBDE congener concentrations within the samples, we found the biota
      SRMs contained primarily tetrabrominated and pentabrominated diphenyl ethers,
      whereas the sediment SRMs contained primarily decabromodiphenyl ether (BDE 209).
      The cod-liver oil (SRM 1588b) and whale blubber (SRM 1945) materials were also
      found to contain measurable concentrations of two methoxylated PBDEs (MeO-BDEs).
      Certified and reference concentrations are reported for 12 PBDE congeners
      measured in the biota SRMs and reference values are available for two MeO-BDEs.
      Results from a sediment interlaboratory comparison PBDE exercise are available
      for the two sediment SRMs (1941b and 1944).

PMID- 17206408
TI  - Therapeutic potential and mechanism of kinetin as a treatment for the human
      splicing disease familial dysautonomia.
AB  - Mutations that affect the splicing of pre-mRNA are a major cause of human
      disease. Familial dysautonomia (FD) is a recessive neurodegenerative disease
      caused by a T to C transition at base pair 6 of IKBKAP intron 20. This mutation
      results in variable tissue-specific skipping of exon 20. Previously, we reported
      that the plant cytokinin kinetin dramatically increases exon 20 inclusion in RNA
      isolated from cultured FD cells. The goal of the current study was to investigate
      the nature of the FD splicing defect and the mechanism by which kinetin improves
      exon inclusion, as such knowledge will facilitate the development of future
      therapeutics aimed at regulating mRNA splicing. In this study, we demonstrate
      that treatment of FD lymphoblast cell lines with kinetin increases IKBKAP mRNA
      and IKAP protein to normal levels. Using a series of minigene constructs, we show
      that deletion of a region at the end of IKBKAP exon 20 disrupts the ability of
      kinetin to improve exon inclusion, pinpointing a kinetin responsive sequence
      element. We next performed a screen of endogenously expressed genes with multiple
      isoforms resulting from exon skipping events and show that kinetin's ability to
      improve exon inclusion is not limited to IKBKAP. Lastly, we highlight the
      potential of kinetin for the treatment of other human splicing disorders by
      showing correction of a splicing defect in neurofibromatosis.

PMID- 17206410
TI  - Detection of labeled abasic sites in damaged DNA by capillary electrophoresis
      with laser-induced fluorescence.
AB  - Removal of nucleobases from the DNA backbone leads to the formation of abasic
      sites. The rate of abasic site formation is significantly increased for
      chemically damaged nucleobases. Thus, abasic sites serve as general biomarkers
      for the quantification of DNA damage. Herein, we show that capillary
      electrophoresis with laser-induced fluorescence (CE-LIF) can be used to detect
      the amount of abasic sites with very high sensitivity. For proof of concept, DNA
      was incubated with methylmethane sulfonate (MMS) and the damaged bases were
      removed by incubation at 80 degrees C. The resulting abasic sites were then
      tagged with a fluorescent aldehyde-reactive probe (FARP). The DNA was
      precipitated with ethanol, and then analyzed by CE-LIF. CE-LIF and HPLC analysis
      shows that the fluorescently tagged DNA (DNA-FARP) had a peak area directly
      proportional to the amount of N-7 methyl guanines. The CE-LIF method had a
      detection limit of 1.2 abasic sites per 1,000,000 bases or ca. 20 attomoles of
      abasic sites. This provides a general method for detecting DNA damage that is not
      only faster but also has comparable or better sensitivity than the alternative
      ELISA-like method.

PMID- 17206411
TI  - Fate of the abstracts presented at three Spanish clinical pharmacology congresses
      and reasons for unpublished research.
AB  - OBJECTIVES: To assess the publication rate of abstracts at 5 years after their
      presentation at three consecutive clinical pharmacology congresses and to examine
      the reasons relating to the lack of publication. METHODS: Oral and poster
      presentations from the congresses of the Spanish Society of Clinical Pharmacology
      (SSCP) in 1994, 1996, and 1998 were reviewed. Authors were contacted to determine
      the fate of their presented studies and the reasons for not publishing them.
      Publications of abstracts with unknown fate were searched the in PubMed database.
      Determinants of publication were examined by Cox regression. RESULTS: In all, 248
      abstracts were analysed. The cumulative publication rate at 5 years was 26%, and
      the median time for publication was 18 months (range: 2-60). The European Journal
      of Clinical Pharmacology was the English language medical journal where most
      abstracts were published. The median impact factor of the articles published was
      1.96 (range: 0.29-8.32). The author survey identified a lack of time (38.2%) and
      a lack of interest (33.3%) as the main reasons for failure to publish. The only
      predictor of an abstract's publication was to be affiliated with a university
      department (hazard ratio: 1.98, 95% confidence interval: 1.20-3.27). CONCLUSIONS:
      Only one-quarter of the abstracts presented at SSCP congresses were subsequently
      published. A lack of time and interest were the main reasons given for not
      submitting these presentations for publication. Authors, scientific societies and
      editorial boards should enhance publications as full papers in peer-reviewed
      journals of the abstracts presented at meetings.

PMID- 17206412
TI  - BoLA class I allele diversity and polymorphism in a herd of cattle.
AB  - Major histocompatibility complex class I genes are among the most polymorphic
      genes characterized. The high level of polymorphism is essential for generating
      host immune responses. In humans, three distinct genomic loci encode human
      leukocyte antigen (HLA) class I genes, allowing individuals to express up to six
      different HLA class I molecules. In cattle, the number of distinct genomic loci
      are currently at least six, and the number of different bovine leukocyte antigens
      (BoLA) class I molecules that are expressed in individual animals are variable.
      The extent of allele variation within the cattle population is unknown. In this
      study, the number and variety of BoLA class I sequences expressed by 36
      individuals were determined from full-length BoLA class I cDNA clones. Twenty
      distinct BoLA class I alleles were identified, with only four being previously
      reported. The number of expressed BoLA class I alleles in individual animals
      ranged between one and four, with none of the animals having an identical
      complement of BoLA class I molecules. Variation existed in the number of BoLA
      class I alleles expressed as well as the composition of expressed alleles,
      however, several BoLA class I alleles were found in multiple individual animals.
      Polymorphic amino acid sites were analyzed for positive and negative selection
      using the ADAPTSITE program. In the antigen recognition sites (ARS), there were
      eight positions that were predicted to be under positive selection and three
      positions that were predicted to be under negative selection from 62 positions.
      In contrast, for non-antigen recognition sites (non-ARS), there were three
      positions that were predicted to be under positive selection and 20 that were
      predicted to be under negative selection from 278, indicating that positive
      selection of amino acids occurs at a greater frequency within the antigen
      recognition sites.

PMID- 17206413
TI  - Assessment of coronary flow reserve by sestamibi imaging in patients with typical
      chest pain and normal coronary arteries.
AB  - PURPOSE: We assessed coronary flow reserve (CFR) by sestamibi imaging in patients
      with typical chest pain, positive exercise stress test and normal coronary
      vessels. METHODS: Thirty-five patients with typical chest pain and normal
      angiogram and 12 control subjects with atypical chest pain underwent
      dipyridamole/rest (99m)Tc-sestamibi imaging. Myocardial blood flow (MBF) was
      estimated by measuring first transit counts in the pulmonary artery and
      myocardial counts from SPECT images. Estimated CFR was expressed as the ratio of
      stress to rest MBF. Rest MBF and CFR were corrected for rate-pressure product
      (RPP) and expressed as normalised MBF (MBF(n)) and normalised CFR (CFR(n)).
      Coronary vascular resistances (CVR) were calculated as the ratio between mean
      arterial pressure and estimated MBF. RESULTS: At rest, estimated MBF and MBF(n)
      were lower in controls than in patients (0.98 +/- 0.4 vs 1.30 +/- 0.3
      counts/pixel/s and 1.14 +/- 0.5 vs 1.64 +/- 0.6 counts/pixel/s, respectively,
      both p < 0.02). Stress MBF was not different between controls and patients (2.34
      +/- 0.8 vs 2.01 +/- 0.7 counts/pixel/s, p=NS). Estimated CFR was 2.40 +/- 0.3 in
      controls and 1.54 +/- 0.3 in patients (p < 0.0001). After correction for the RPP,
      CFR(n) was still higher in controls than in patients (2.1 +/- 0.5 vs 1.29 +/-
      0.5, p < 0.0001). At baseline, CVR values were lower (p < 0.01) in patients than
      in controls. Dipyridamole-induced changes in CVR were greater (p < 0.0001) in
      controls (-63%) than in patients (-35%). In the overall study population, a
      significant correlation between dipyridamole-induced changes in CVR and CFR was
      observed (r = -0.88, p < 0.0001). CONCLUSION: SPECT might represent a useful non
      invasive method for assessing coronary vascular function in patients with angina
      and a normal coronary angiogram.

PMID- 17206414
TI  - Should FDG-PET imaging be considered on a routine basis in clinical trials for
      carcinoma of esophagus to assure uniformity of protocols among sites?

PMID- 17206415
TI  - Non-invasive visualisation of the development of peritoneal carcinomatosis and
      tumour regression after 213Bi-radioimmunotherapy using bioluminescence imaging.
AB  - PURPOSE: Non-invasive imaging of tumour development remains a challenge,
      especially for tumours in the intraperitoneal cavity. Therefore, the aim of this
      study was the visualisation of both the development of peritoneal carcinomatosis
      and tumour regression after radioimmunotherapy with tumour-specific 213Bi
      Immunoconjugates, via in vivo bioluminescence imaging of firefly luciferase
      transfected cells. METHODS: Human diffuse-type gastric cancer cells expressing
      mutant d9-E-cadherin were stably transfected with firefly luciferase (HSC45-M2
      luc). For bioluminescence imaging, nude mice were inoculated intraperitoneally
      with 1x10(7) HSC45-M2-luc cells. On days 4 and 8 after tumour cell inoculation,
      imaging was performed following D-luciferin injection using a cooled CCD camera
      with an image intensifier unit. For therapy, mice were injected with 2.7 MBq
      213Bi-d9MAb targeting d9-E-cadherin on day 8 after tumour cell inoculation.
      Bioluminescence images were taken every 4 days to monitor tumour development.
      RESULTS: After i.p. inoculation of HSC45-M2-luc cells into nude mice, development
      as well as localisation of peritoneal carcinomatosis could be visualised using
      bioluminescence imaging. Following 213Bi-d9MAb therapy on day 8 after
      intraperitoneal inoculation of HSC45-M2-luc cells, small tumour nodules were
      totally eliminated and larger nodules showed a clear reduction in size on day 12
      after tumour cell inoculation. Subsequently a recurrence of tumour mass was
      observed, starting from the remaining tumour spots. By measuring the mean grey
      level intensity, tumour development over time could be demonstrated. CONCLUSION:
      Non-invasive bioluminescence imaging permits visualisation of the development of
      peritoneal carcinomatosis, localisation of tumour in the intraperitoneal cavity
      and evaluation of therapeutic success after 213Bi-d9MAb treatment.

PMID- 17206416
TI  - In vivo evaluation of 2'-deoxy-2'-[(18)F]fluoro-5-iodo-1-beta-D
      arabinofuranosyluracil ([18F]FIAU) and 2'-deoxy-2'-[18F]fluoro-5-ethyl-1-beta-D
      arabinofuranosyluracil ([18F]FEAU) as markers for suicide gene expression.
AB  - PURPOSE: FIAU and FEAU were evaluated in vitro and in vivo as markers for HSV1-tk
      gene expression. METHODS: In vitro and biodistribution studies were performed in
      wild type and transduced HT-29 cells using [14C]FIAU and [3H]FEAU. PET imaging
      was performed using [18F]FIAU and [18F]FEAU. RESULTS: In vitro uptake of
      [14C]FIAU in tk-positive cells was 39-fold, 49-fold, and 43-fold higher (p<0.001)
      than in wild type cells at 30, 60, and 120 min, respectively. Uptake of [3H]FEAU
      in transduced cells was 46-fold, 62-fold, and 121-fold higher (p<0.001) than in
      wild type cells at the same time points. In vivo uptake of [14C]FIAU at 2 h in
      HSV1-tk positive tumors was 15.48+/-3.94, 6.7-fold higher (p<0.001) than in wild
      type tumors. Uptake of [3H]FEAU in transduced tumors was 9.98+/-1.99, 5.0-fold
      higher (p<0.001) than in wild type tumors. Micro-PET images using [18F]FIAU and
      [18F]FEAU also showed very high uptake in HSV-tk tumors. CONCLUSION: [18F]FIAU
      and [18F]FEAU appear to be potential PET imaging agents for gene expression.

PMID- 17206417
TI  - Medial impingement after ankle replacement.
AB  - Ankle replacements appear to offer a good alternative to fusion for most
      arthritic conditions. Use of mobile bearings has significantly improved results
      of ankle replacement. Ankle replacements still have a significant minor
      complication rate which does not seem to affect the long-term outcome. Medial
      impingement as a complication has been reported with popular designs. We reviewed
      the senior author's first five years of Buechel-Pappas ankle replacements looking
      at AOFAS scores, VAS scores, patient satisfaction, learning curve of the surgeon
      and complications. Eight patients out of a total of 34 reported symptoms of
      medial impingement at follow-up. Four patients underwent revision surgery for
      this. Ankle replacements have a significant proportion of minor complications,
      one of which is medial impingement. Whether this is due to implant design,
      residual arthritis in medial recess or soft-tissue pathology is uncertain but
      revision surgery may be required.

PMID- 17206418
TI  - For Dr. Choi's Epub study "Combination index of sTfR and MCH for evaluating iron
      deficiency in end-stage renal disease".

PMID- 17206419
TI  - Cytogenetics detects infiltrations of a primary cutaneous acute myeloid leukemia
      to the kidney.
AB  - Extramedullary manifestations of acute myeloid leukemia (AML) are rare and
      commonly involve one tissue. We report of a cutaneous acute myelomonocytic
      leukemia infiltrating the kidney next to the skin. A 61-year-old female patient
      with complex karyotype cutaneous AML FAB M4 underwent abdominal computed
      tomography scans. A lesion in her left kidney appeared suspicious of renal
      carcinoma as confirmed by histology. However, fluorescence in situ hybridization
      cytogenetics revealed a chromosome 11q23 abnormality in the nephrectomy specimen,
      which also appeared in the leukemic blasts of skin and bone marrow. Closer
      histomorphologic workup revealed an infiltration of the kidney with leukemia.
      This case report illustrates how modern diagnostic procedures can help to reveal
      rare sites of disease.

PMID- 17206420
TI  - Accuracy of automated volumetry of pulmonary nodules across different multislice
      CT scanners.
AB  - The purpose of this study was to compare the accuracy of an automated volumetry
      software for phantom pulmonary nodules across various 16-slice multislice spiral
      CT (MSCT) scanners from different vendors. A lung phantom containing five
      different nodule categories (intraparenchymal, around a vessel, vessel attached,
      pleural, and attached to the pleura), with each category comprised of 7-9 nodules
      (total, n = 40) of varying sizes (diameter 3-10 mm; volume 6.62 mm(3)-525 mm(3)),
      was scanned with four different 16-slice MSCT scanners (Siemens, GE, Philips,
      Toshiba). Routine and low-dose chest protocols with thin and thick collimations
      were applied. The data from all scanners were used for further analysis using a
      dedicated prototype volumetry software. Absolute percentage volume errors (APE)
      were calculated and compared. The mean APE for all nodules was 8.4% (+/-7.7%) for
      data acquired with the 16-slice Siemens scanner, 14.3% (+/-11.1%) for the GE
      scanner, 9.7% (+/-9.6%) for the Philips scanner and 7.5% (+/-7.2%) for the
      Toshiba scanner, respectively. The lowest APEs were found within the diameter
      size range of 5-10 mm and volumes >66 mm(3). Nodule volumetry is accurate with a
      reasonable volume error in data from different scanner vendors. This may have an
      important impact for intraindividual follow-up studies.

PMID- 17206421
TI  - Extracranial applications of diffusion-weighted magnetic resonance imaging.
AB  - Diffusion-weighted MRI has become more and more popular in the last couple of
      years. It is already an accepted diagnostic tool for patients with acute stroke,
      but is more difficult to use for extracranial applications due to technical
      challenges mostly related to motion sensitivity and susceptibility variations
      (e.g., respiration and air-tissue boundaries). However, thanks to the newer
      technical developments, applications of body DW-MRI are starting to emerge. In
      this review, we aim to provide an overview of the current status of the published
      data on DW-MRI in extracranial applications. A short introduction to the physical
      background of this promising technique is provided, followed by the current
      status, subdivided into three main topics, the functional evaluation, tissue
      characterization and therapy monitoring.

PMID- 17206422
TI  - Molecular cardiovascular imaging using scintigraphic methods.
AB  - Molecular cardiovascular imaging plays an increasingly important role both in
      basic research and in clinical diagnosis. Scintigraphic methods have long been
      used to study pathophysiological changes on a cellular and molecular level, and
      they are likely to remain important molecular imaging modalities in the
      foreseeable future. This article provides an overview over current developments
      in cardiovascular molecular imaging using scintigraphic methods. The focus lies
      on imaging of cardiac innervation, plaque instability, hypoxia and angiogenesis,
      gene expression and stem and progenitor cell migration and proliferation.

PMID- 17206423
TI  - Multislice computed tomography: angiographic emulation versus standard assessment
      for detection of coronary stenoses.
AB  - The present study investigated angiographic emulation of multislice computed
      tomography (MSCT) (catheter-like visualization) as an alternative approach of
      analyzing and visualizing findings in comparison with standard assessment. Thirty
      patients (120 coronary arteries) were randomly selected from 90 prospectively
      investigated patients with suspected coronary artery disease who underwent MSCT
      (16-slice scanner, 0.5 mm collimation, 400 ms rotation time) prior to
      conventional coronary angiography for comparison of both approaches. Sensitivity
      and specificity of angiographic emulation [81% (26/32) and 93% (82/88)] were not
      significantly different from those of standard assessment [88% (28/32) and 99%
      (87/88)], while the per-case analysis time was significantly shorter for
      angiographic emulation than for standard assessment (3.4 +/- 1.5 vs 7.0 +/- 2.5
      min, P < 0.001). Both interventional and referring cardiologists preferred
      angiographic emulation over standard curved multiplanar reformations of MSCT
      coronary angiography for illustration, mainly because of improved overall
      lucidity and depiction of sidebranches (P < 0.001). In conclusion, angiographic
      emulation of MSCT reduces analysis time, yields a diagnostic accuracy comparable
      to that of standard assessment, and is preferred by cardiologists for
      visualization of results.

PMID- 17206424
TI  - A novel technique in selective venous sampling in the localization of parathyroid
      tumours utilizing a micro-wire and standardized catheter.
AB  - Selective venous sampling (SVS) is a useful technique to localize a number of
      hormone-producing tumours, such as parathyroid tumours, when other imaging
      techniques are inconclusive. Typically, a 5 French selective single end-hole
      catheter and standard hydrophilic wire are utilized to access the required
      vessels and an attempt made to withdraw blood. However, most interventional
      radiologists are familiar with the difficulty and limited success in withdrawing
      venous blood through an end-hole catheter. We describe a simple, cheap and novel
      technique utilizing a micro-wire that we have developed in our interventional
      suite to overcome this common problem. Having reached the target site with the
      selective end-hole catheter, a Tuohy Borst adapter is attached to the catheter
      end. A 0.018-inch micro-wire is then inserted through the selective end-hole
      catheter such that the distal wire tip exits the distal catheter tip. The purpose
      of the micro-wire exiting the catheter is to both straighten the catheter tip to
      a position parallel to the vessel, allowing easier aspiration as well as
      physically preventing blockage of the catheter by the vein intimal wall collapse
      on suction. The 5-ml sample required for PTH assay is then successfully obtained
      via the Tuohy Borst adapter.

PMID- 17206425
TI  - Imaging of Budd-Chiari syndrome.
AB  - Budd-Chiari syndrome occurs when venous outflow from the liver is obstructed. The
      obstruction may occur at any point from the hepatic venules to the left atrium.
      The syndrome most often occurs in patients with underlying thrombotic disorders
      such as polycythemia rubra vera, paroxysmal nocturnal hemoglobinuria and
      pregnancy. It may also occur secondary to a variety of tumours, chronic
      inflammatory diseases and infections. Imaging plays an important role both in
      establishing the diagnosis of Budd-Chiari syndrome as well as evaluating for
      underlying causes and complications such as portal hypertension. In this review
      article, we discuss the role of modern imaging in the evaluation of Budd-Chiari
      syndrome.

PMID- 17206426
TI  - Neglectable benefit of searching for incidental findings in the Dutch-Belgian
      lung cancer screening trial (NELSON) using low-dose multidetector CT.
AB  - The purpose of this study was to prospectively determine the frequency and
      spectrum of incidental findings (IFs) and their clinical implications in a high
      risk population for lung cancer undergoing low-dose multidetector computed
      tomography (MDCT) screening for lung cancer. Scans of 1,929 participants were
      evaluated for lung lesions and IFs by two radiologists. IFs were categorised as
      not clinically relevant or possibly clinically relevant. Findings were considered
      possibly clinically relevant if they could require further evaluation or could
      have substantial clinical implications. All possibly clinically relevant IFs were
      reviewed by a third radiologist, who determined its clinical relevance. Of all
      1,929 participants, 1,410 (73%) had not clinically relevant IFs and 163 (8%) had
      possibly clinically relevant IFs of which 129 (79%) were indeed considered
      clinically relevant. Additional imaging was performed mainly by ultrasound (112
      of 118, 96%). All but one lesion were concluded to be benign, mostly cysts (n =
      115, 80%). Only 21 (1%) participants had findings with clinical implications. In
      one participant a malignancy was found, yet without any clinical benefit since no
      curative treatment was possible. Based on our results, we advise against
      systematically searching for and reporting of IFs in lung cancer screening
      studies using low-dose MDCT.

PMID- 17206427
TI  - Characterization of myocardial viability using MR and CT imaging.
AB  - Cardiovascular magnetic resonance (MR) imaging is of proven clinical value for
      the noninvasive characterization of myocardial viability. Computed tomography
      (CT) is also being exploited for this indication. Examples of each of these
      imaging strategies for the assessment of myocardial viability will be provided in
      this review. Key MRI concepts and practical considerations such as customized MR
      imaging techniques and tailored imaging protocols dedicated to viability
      assessment are outlined with the primary focus on recent developments. Clinical
      applications of MR-based viability assessment are reviewed, ranging from rapid
      functional cine imaging to tissue characterization using T2-weighted imaging and
      T1-weighted late-contrast-enhanced imaging. Next, the merits and limitations of
      state-of-the-art CT imaging are surveyed, and their implications for viability
      assessment are considered. The final emphasis is on current trends and future
      directions in noninvasive viability assessment using MRI and CT.

PMID- 17206428
TI  - Cell labeling with the positive MR contrast agent Gadofluorine M.
AB  - The purpose of this study was to label human monocytes with Gadofluorine M by
      simple incubation for subsequent cell depiction at 1.5 and 3 T. Gadofluorine M
      displays a high r(1) relaxivity and is spontaneously phagocytosed by macrophages.
      Human monocytes were incubated with Gadofluorine M-Cy at varying concentrations
      and incubation times and underwent MR imaging at 1.5 and 3 T at increasing time
      intervals after the labeling procedure. R1-relaxation rates and r1 relaxivities
      of the labeled cells and non-labeled controls were determined. Cellular contrast
      agent uptake was examined by fluorescence microscopy and quantified by ICP-AES.
      Efficient cell labeling was achieved after incubation of the cells with 25 mM Gd
      Gadofluorine M for 12 h, resulting in a maximal uptake of 0.3 fmol Gd/cell
      without impairment of cell viability. Fluorescence microscopy confirmed
      internalization of the fluorescent contrast agent by monocytes. The r1 relaxivity
      of the labeled cells was 137 mM(-1)s(-1) at 1.5 T and 80.46 mM(-1)s(-1) at 3 T.
      Imaging studies showed stable labeling for at least 7 days. Human monocytes can
      be effectively labeled for MR imaging with Gadofluorine M. Potential in vivo cell
      tracking applications include targeting of inflammatory processes with
      Gadofluorine-labeled leukocytes or monitoring of stem cell therapies for the
      treatment of arthritis.

PMID- 17206429
TI  - Coronary artery stent geometry and in-stent contrast attenuation with 64-slice
      computed tomography.
AB  - We aimed at assessing stent geometry and in-stent contrast attenuation with 64
      slice CT in patients with various coronary stents. Twenty-nine patients (mean age
      60 +/- 11 years; 24 men) with 50 stents underwent CT within 2 weeks after stent
      placement. Mean in-stent luminal diameter and reference vessel diameter proximal
      and distal to the stent were assessed with CT, and compared to quantitative
      coronary angiography (QCA). Stent length was also compared to the manufacturer's
      values. Images were reconstructed using a medium-smooth (B30f) and sharp (B46f)
      kernel. All 50 stents could be visualized with CT. Mean in-stent luminal diameter
      was systematically underestimated with CT compared to QCA (1.60 +/- 0.39 mm
      versus 2.49 +/- 0.45 mm; P < 0.0001), resulting in a modest correlation of QCA
      versus CT (r = 0.49; P < 0.0001). Stent length as given by the manufacturer was
      18.2 +/- 6.2 mm, correlating well with CT (18.5 +/- 5.7 mm; r = 0.95; P < 0.0001)
      and QCA (17.4 +/- 5.6 mm; r = 0.87; P < 0.0001). Proximal and distal reference
      vessel diameters were similar with CT and QCA (P = 0.06 and P = 0.03). B46f
      kernel images showed higher image noise (P < 0.05) and lower in-stent CT
      attenuation values (P < 0.001) than images reconstructed with the B30f kernel. 64
      slice CT allows measurement of coronary artery in-stent density, and
      significantly underestimates the true in-stent diameter compared to QCA.

PMID- 17206430
TI  - Actual role of endobronchial ultrasound (EBUS).
AB  - Many pathologies of the airway involve the bronchial wall and the parabronchial
      structures. The view of the endoscopist, however, is limited to the lumen and the
      internal surface of the airway. Processes within the airway wall and outside the
      airway can only be assessed by indirect signs. Especially in malignancies, this
      can be of decisive importance for the fate of the patient. Therefore, expanding
      the endoscopist's view beyond the airway is essential. Endobronchial ultrasound
      (EBUS) and endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA)
      are new diagnostic tools that are available on the market. They have great
      potential for diagnosis of mediastinal processes and staging of lung cancer.
      After discovering a lung cancer without extrathoracic metastases, the
      preoperative mediastinal check-up is of great importance in determining
      operability. The investigation of a suspected malignant adenopathy justifies a
      complete examination by mediastinoscopy or mediastinotomy, which are considered
      gold standards. EBUS-TBNA constitutes the recent evolution of TBNA, a method
      known for 20 years now but underused. The aim of this review is to highlight to
      the different techniques and to discuss the results of published trials.

PMID- 17206431
TI  - Ball valve obstruction of a bronchus causing lobar emphysema in a neonate.
AB  - Lobar emphysema in the neonate is usually congenital, resulting from cartilage
      deficiency causing bronchomalacia and distal air trapping. Acquired forms are
      usually associated with chronic lung disease or endobronchial obstruction such as
      mucus plugging. We report a pedunculated endobronchial polyp in a 2-month old ex
      premature infant causing intermittent hyperinflation of the right middle lobe.
      The polyp was seen prolapsing in and out of the bronchus intermedius at
      bronchoscopy. Possible aetiological links with mechanical ventilation are
      discussed. We also emphasise the value of bronchoscopy prior to lobectomy in
      cases of congenital lobar emphysema (CLE).

PMID- 17206432
TI  - Serum monocyte chemotactic protein-1 levels in congenital diaphragmatic hernia.
AB  - To measure serum monocyte chemotactic protein-1 (MCP-1) in patients with
      congenital diaphragmatic hernia (CDH) and investigate its relationship to the
      development of persistent pulmonary hypertension (PPH). Serum MCP-1 was measured
      in 13 neonates with high risk for CDH at the time of diagnosis and
      postoperatively, and in five age-matched controls using an ELISA system. The 13
      CDH subjects were divided into four groups according to the presence of PPH and
      outcome. Group I (severe-pre group): subjects with severe PPH who died prior to
      surgery (n = 5); Group II (mild-pre group): subjects with mild PPH controlled by
      medications (n = 8); Group IIa (severe-post group): subjects who subsequently
      developed severe PPH postoperatively and died (n = 3); and Group IIb (mild-post
      group): subjects who continued to have mild PPH controlled by medications. We
      also examined nitrofen-induced hypoplastic lungs from five rat fetuses with CDH
      and five control lung specimens for MCP-1 using immunohistochemistry. Mean serum
      MCP-1 in Group I was (1038.0 +/- 95.8 pg/ml), which was significantly higher than
      Group II (444.9 +/- 39.7 pg/ml) (P < 0.0001) and controls (147.3 +/- 11.3 pg/ml)
      (P < 0.0001). Postoperatively, Group IIa was significantly higher than Group IIb
      from 24 to 120 h postoperatively (P < 0.001). In Group IIb serum MCP-1 did not
      rise at all between 24 and 120 h postoperatively. Hypoplastic fetal rat CDH lungs
      had strong expression of MCP-1 compared with control lungs. Up-regulated
      expression and high circulating levels of MCP-1 in CDH patients with PPH suggest
      that MCP-1 may play a role in the development of PPH in CDH.

PMID- 17206433
TI  - Genetic diversity of 10 X chromosome STRs in northern Portugal.
AB  - Genetic data of 10 X chromosome STRs (DXS8378, DXS9898, DXS8377, HPRTB,
      GATA172D05, DXS7423, DXS6809, DXS7132, DXS101 and DXS6789) were obtained in a
      sample of unrelated males born in the five northern Portuguese districts. In a
      global sample of 347 individuals, no shared haplotypes were found for this set of
      markers and single locus gene diversities were high, varying between 0.678 for
      DXS7423 and 0.921 for DXS8377. Linkage disequilibrium analysis did not reveal
      consistent evidence of association between the X-STRs used. Population
      comparisons of northern Portuguese districts (exact test of population
      differentiation; pairwise genetic distances) and analysis of molecular variance
      supported genetic homogeneity of this region and therefore a common genetic
      database was considered. In comparisons with other European data, the only
      population samples showing statistically significant differences to northern
      Portugal were Germany and Latvia. The present work demonstrates that these
      genetic markers are highly discriminating and therefore useful for human
      identification purposes and anthropological research.

PMID- 17206434
TI  - Postmortem determination of concentrations of stress hormones in various body
      fluids--is there a dependency between adrenaline/noradrenaline quotient, cause of
      death and agony time?
AB  - To find out whether a certain cause of death or a certain length of an agonal
      period shows specific adrenaline or noradrenaline profiles, heart blood, femoral
      vein blood, liquor, urine and vitreous humour were taken from corpses (n = 98) at
      the Medical School Hannover, and noradrenaline and adrenaline were determined
      using high-performance liquid chromatography (HPLC). Corpses were classified
      according to the following five categories: short agony, long agony, state after
      hanging, state after asphyxiation and state after CPR with documented
      administration of epinephrine. Once results were collected the
      adrenaline/noradrenaline quotient was determined. It became clear that there were
      no significant differences regarding the concentration of adrenaline and
      noradrenaline in the various body fluids in relation to the above-mentioned
      categories. The means adrenaline/noradrenaline quotients in femoral vein blood
      were 0.21 +/- 0.29 for hanged persons, 0.38 +/- 0.47 for asphyxiated persons,
      0.17 +/- 0.19 for those with short agony and 0.42 +/- 0.43 for those with long
      agony, significantly below 1 (p < 0.001; p = 0.001; p = 0.003). For condition
      after CPR we found an adrenaline/noradrenaline quotient of 2.81 +/- 5.8. In
      liquor the adrenaline/noradrenaline quotients for short agony was 0.17 +/- 0.17,
      for hanged persons 0.18 +/- 0.19 and for asphyxiated ones 0.30 +/- 0.38,
      significantly lower than 1 (p < 0.001). In urine the adrenaline/noradrenaline
      quotients for all categories are lower than 1 (p < 0.001); short agony (0.13 +/-
      0.09), long agony (0.21 +/- 0.16), hanged (0.15 +/- 0.16), asphyxiated (0.14 +/-
      0.08) and CPR (0.14 +/- 0.06). In vitreous humour the quotients for short agony
      (0.14 +/- 0.28), long agony (0.13 +/- 0.12), hanged (0.07 +/- 0.09) and
      asphyxiated (0.09 +/- 0.11) are lower than 1 (p < 0.001). The spread of data for
      the adrenaline/noradrenaline quotient did not allow for any conclusions about
      cause of death and length of agony in individual cases.

PMID- 17206435
TI  - Clinical forensic radiology in strangulation victims: forensic expertise based on
      magnetic resonance imaging (MRI) findings.
AB  - Based on only one objective and several subjective signs, the forensic
      classification of strangulation incidents concerning their life-threatening
      quality can be problematic. Reflecting that it is almost impossible to detect
      internal injuries of the neck with the standard forensic external examination, we
      examined 14 persons who have survived manual and ligature strangulation or
      forearm choke holds using MRI technique (1.5-T scanner). Two clinical
      radiologists evaluated the neck findings independently. The danger to life was
      evaluated based on the "classical" external findings alone and in addition to the
      radiological data. We observed hemorrhaging in the subcutaneous fatty tissue of
      the neck in ten cases. Other frequent findings were hemorrhages of the neck and
      larynx muscles, the lymph nodes, the pharynx, and larynx soft tissues. Based on
      the classical forensic strangulation findings with MRI, eight of the cases were
      declared as life-endangering incidents, four of them without the presence of
      petechial hemorrhage but with further signs of impaired brain function due to
      hypoxia. The accuracy of future forensic classification of the danger to life
      will probably be increased when it is based not only on one objective and several
      subjective signs but also on the evidence of inner neck injuries. However,
      further prospective studies including larger cohorts are necessary to clarify the
      value of the inner neck injuries in the forensic classification of surviving
      strangulation victims.

PMID- 17206436
TI  - Change in airway responsiveness over a workweek in organic waste loaders.
AB  - OBJECTIVE: Organic waste workers are exposed to high endotoxin levels that may
      result in respiratory health effects. This study describes changes in lung
      function and methacholine airway responsiveness over a workweek in household
      organic waste loaders. METHODS: Assessment of lung function and methacholine
      airway responsiveness before and after a workweek in six organic waste loaders
      with and ten loaders without regular respiratory symptoms. Methacholine
      responsiveness was expressed as dose-response slope, i.e. % fall in FEV(1) per mg
      methacholine compared to either the post-saline value (DRS(sal)), or the highest
      FEV(1) (DRS(max)). RESULTS: Monday morning, FEV(1) was similar in cases and
      controls. Over the workweek, FEV(1) and MMEF decreased slightly in both cases and
      controls (P > 0.10). In contrast, DRS increased in cases and decreased in control
      subjects (P < 0.10). The difference in % change of DRS was statistically
      significant after adjustment for smoking and age. CONCLUSION: Our results suggest
      exaggeration of pre-existent airway inflammation during the workweek in organic
      waste loaders with regular respiratory symptoms. This needs confirmation in
      larger studies.

PMID- 17206437
TI  - Mitochondrial coupling in humans: assessment of the P/O2 ratio at the onset of
      calf exercise.
AB  - Coupling of oxidation to ATP synthesis (P/O2 ratio) is a critical step in the
      conversion of carbon substrates to fuel (ATP) for cellular activity. The ability
      to quantitatively assess mitochondrial coupling in vivo can be a valuable tool
      for basic research and clinical purposes. At the onset of a square wave moderate
      exercise, the ratio between absolute amount of phosphocreatine split and O2
      deficit (corrected for the amount of O2 released from the body O2 stores and in
      the absence of lactate production), is the mirror image of the P/O2 ratio. To
      calculate this value, cardiac output (Q), whole body O2 uptake (VO2), O2 deficit
      (O2(def)) and high-energy phosphates concentration (by 31P-NMR spectroscopy) in
      the calf muscles were measured on nine healthy volunteers at rest and during
      moderate intensity plantar flexion exercise (3.44 +/- 0.73 W per unit active
      muscle mass). Q and VO2 increased (from 4.68 +/- 1.56 to 5.83 +/- 1.59 l min(-1)
      and from 0.28 +/- 0.05 to 0.48 +/- 0.09 l min(-1), respectively), while
      phosphocreatine (PCr) concentration decreased significantly (22 +/- 6%) from rest
      to steady-state exercise. For each volunteer, "gross" O2(def) was corrected for
      the individual changes in the venous blood O2 stores (representing 49.9 +/- 9.5%
      of the gross O2(def)) yielding the "net" O2(def). Resting PCr concentration was
      estimated from the appropriate spectroscopy data. The so calculated P/O2 ratio
      amounted on average to 4.24 +/- 0.13 and was, in all nine subjects, very close to
      the literature values obtained directly on intact skeletal muscle. This unfolds
      the prospect of a non-invasive tool to quantitatively study mitochondrial
      coupling in vivo.

PMID- 17206438
TI  - High-energy phosphate metabolism in the calf muscle of healthy humans during
      incremental calf exercise with and without moderate cuff stenosis.
AB  - It is known that the relevance of a peripheral stenosis for muscle function
      increases with exercise. Our intention was to investigate the impact of a
      moderate cuff stenosis (CS) at 120 mmHg of the superficial femoral artery on high
      energy phosphate (HEP) metabolism during isotonic, incremental calf exercise.
      Serial phosphorus 31 magnetic resonance spectroscopy (31P MRS) and velocity
      encoded phase-contrast MR imaging (VEPC MRI) were carried out in each leg of ten
      healthy male volunteers. Each leg underwent four increments of calf exercise (2,
      3, 4 and 5 W) followed by recovery during separate exercise sessions with and
      without a CS at 120 mmHg. The serial 31P MRS measurements had a time resolution
      of 10 s. VEPC MRI was performed at the end of each increment during separate
      sessions. During all increments, we detected significant differences (P < 0.05)
      in the phosphocreatine (PCr) time constants and the amount of PCr hydrolysis
      between the sessions without and with CS. Regarding the time courses of the PCr,
      inorganic phosphate (Pi) and pH level, we observed significant differences (P <
      0.002) during exercise and recovery. During both conditions, the end-increment
      PCr levels as well as blood flow correlated significantly with the mechanical
      power. The PCr time constants during exercise significantly correlated with the
      intramuscular pH, but not with blood flow or mechanical power. However, the PCr
      recovery time constants correlated significantly with blood flow and end-exercise
      pH. Our study shows that reduction of blood flow due to a peripheral stenosis
      results in a prolongation of PCr time constants, decreased PCr and pH level as
      well as increased Pi level during exercise. We believe that 31P MRS during
      incremental exercise might provide additional information for assessing the
      relevance of a peripheral stenosis and its impact on muscle function.

PMID- 17206439
TI  - Acute effects of hyperglycaemia with and without exercise on endothelial function
      in healthy young men.
AB  - Post-prandial hyperglycaemia impairs endothelial function as evaluated by
      brachial artery flow-mediated dilation (FMD). Exercise is an intervention to
      protect against cardiovascular disease and to improve FMD. In this study, we
      examined whether the effect of acute hyperglycaemia on endothelial function in
      healthy young men is restored by aerobic exercise. Using a counterbalanced,
      randomized crossover design, we measured the brachial artery FMD at baseline and
      1, 2, 3 and 4 h after 75 g glucose ingestion in 11 healthy young men, with and
      without a single bout of aerobic exercise. Brachial artery FMD declined from 11.4
      +/- 3.8% at baseline to 7.3 +/- 3.4% 1 h after oral glucose ingestion, and
      returned to baseline after 4 h. When the oral glucose ingestion was followed
      immediately by 45 min of treadmill exercise at an intensity of 60% maximal oxygen
      uptake, FMD demonstrated no significant decrease (11.8 +/- 2.5, 11.3 +/- 2.8,
      12.2 +/- 2.7, 13.5 +/- 3.5, and 12.6 +/- 2.4% at baseline and 4 h after
      ingestion, respectively). The results indicate that the aerobic exercise restores
      the impaired FMD induced by oral glucose ingestion.

PMID- 17206440
TI  - Reduced hypoxic ventilatory response with preserved blood oxygenation in yoga
      trainees and Himalayan Buddhist monks at altitude: evidence of a different
      adaptive strategy?
AB  - Yoga induces long-term changes in respiratory function and control. We tested
      whether it represents a successful strategy for high-altitude adaptation. We
      compared ventilatory, cardiovascular and hematological parameters in: 12
      Caucasian yoga trainees and 12 control sea-level residents, at baseline and after
      2-week exposure to high altitude (Pyramid Laboratory, Nepal, 5,050 m), 38 active
      lifestyle high-altitude natives (Sherpas) and 13 contemplative lifestyle high
      altitude natives with practice of yoga-like respiratory exercises (Buddhist
      monks) studied at 5,050 m. At baseline, hypoxic ventilatory response (HVR), red
      blood cell count and hematocrit were lower in Caucasian yoga trainees than in
      controls. After 14 days at altitude, yoga trainees showed similar oxygen
      saturation, blood pressure, RR interval compared to controls, but lower HVR (
      0.44 +/- 0.08 vs. -0.98 +/- 0.21 l/min/m/%SaO(2), P < 0.05), minute ventilation
      (8.3 +/- 0.9 vs. 10.8 +/- 1.6 l/min, P < 0.05), breathing rate (indicating higher
      ventilatory efficiency), and lower red blood cell count, hemoglobin, hematocrit,
      albumin, erythropoietin and soluble transferrin receptors. Hypoxic ventilatory
      response in monks was lower than in Sherpas (-0.23 +/- 0.05 vs. -0.63 +/- 0.09
      l/min/m/%SaO(2), P < 0.05); values were similar to baseline data of yoga trainees
      and Caucasian controls, respectively. Red blood cell count and hematocrit were
      lower in monks as compared to Sherpas. In conclusion, Caucasian subjects
      practicing yoga maintain a satisfactory oxygen transport at high altitude, with
      minimal increase in ventilation and with reduced hematological changes,
      resembling Himalayan natives. Respiratory adaptations induced by the practice of
      yoga may represent an efficient strategy to cope with altitude-induced hypoxia.

PMID- 17206441
TI  - Mild exercise training, cardioprotection and stress genes profile.
AB  - To improve current knowledge of the molecular mechanisms underlying exercise
      induced cardioprotection in a rat model of mild exercise training, Sprague-Dawley
      rats were trained to run on a treadmill up to 55% of their maximal oxygen uptake
      for 1 h/day, 3 days/week, 14 weeks, with age-matched sedentary controls (n =
      20/group). Rats were sacrificed 48 h after the last training session. Despite
      lack of cardiac hypertrophy, training decreased blood hemoglobin (7.94 +/- 0.21
      mM vs. 8.78 +/- 0.23 mM, mean +/- SE, P = 0.01) and increased both plasma
      malondialdehyde (0.139 +/- 0.005 mM vs. 0.085 +/- 0.009 mM, P = 0.05) and the
      activity of Mn-superoxide dismutase (11.6 +/- 0.6 vs. 16.5 +/- 1.6 mU/microg, P =
      0.01), whereas total superoxide dismutase activity was unaffected. When subjected
      to 30-min ischemia followed by 90-min reperfusion, hearts from trained rats (n =
      5) displayed reduced infarct size as compared to controls (37.26 +/- 0.92% vs.
      49.09 +/- 2.11% of risk area, P = 0.04). The biochemical analyses in the
      myocardium, which included gene expression profiles, real-time PCR, Western blot
      and determination of enzymatic activity, showed training-induced upregulation of
      the following mRNAs and/or proteins: growth-arrest and DNA-damage induced 153
      (GADD153/CHOP), heme-oxygenase-1 (HO-1), cyclooxygenase-2 (Cox-2), heat-shock
      protein 70/72 (HSP70/72), whereas heat-shock protein 60 (HSP60) and glucose
      regulated protein 75 (GRP75) were decreased. As a whole, these data indicate that
      mild exercise training activates a second window of myocardial protection against
      ischemia/reperfusion by upregulating a number of protective genes, thereby
      warranting further investigation in man.

PMID- 17206442
TI  - Revisiting the effect of posture on high-intensity constant-load cycling
      performance in men and women.
AB  - It was recently observed that inclining the body from a supine to upright
      position improved the performance of high-intensity, constant-load cycling to a
      larger extent in men than women (Egana et al. in Eur J Appl Physiol 96:1-9,
      2006), although this gender-related effect was based on a small number of men (n
      = 5) and women (n = 5). To explore this effect further, we studied the effect of
      body tilt on cycling performance in a larger and different group of men (n = 8)
      and women (n = 18). Peak power, peak VO2 and the ventilatory threshold (VT) were
      determined during an upright maximal graded cycle test, and a high-intensity test
      (80% peak power) was performed to failure in both the upright and supine
      positions. Performance was significantly longer in the upright compared with
      supine position in men (17.4 +/- 7.7 vs. 7.6 +/- 3.4 min) and women (14.1 +/- 6.0
      vs. 6.0 +/- 3.7 min). The magnitude of this postural effect was not significantly
      different between men and women; whereas it was significantly correlated with the
      relative intensity of exercise expressed as a function of VT (r = -0.39). These
      data demonstrate that the postural effect on high-intensity cycling performance
      is not influenced by gender; but that it is related to the intensity of exercise
      relative to the ventilatory threshold.

PMID- 17206443
TI  - Biomarkers of muscle and cartilage damage and inflammation during a 200 km run.
AB  - Ultra-marathon running is frequently associated with muscle fibre damage.
      However, ultra-marathon related information is scarce. The present study
      evaluated muscle and cartilage biomarkers, and cytokine secretion during a 200 km
      running event. Venous blood samples from 54 trained male ultra-marathon runners
      (mean +/- SD, 45.7 +/- 5.1 years). Plasma creatine phosphokinase (CPK), lactate
      dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), lactate, glucose, high-sensitivity C-reactive protein (Hs-CRP),
      interleukin-6 (IL-6), TNF- proportional, variant and serum cartilage oligomeric
      matrix protein (COMP) content were determined before, midway and immediately
      after the race. CPK increased 90-fold (19-fold at 100 km) from pre-race value and
      LDH increased 3.7-fold (2.2-fold at 100 km). AST increased 15-fold (5-fold at 100
      km) and ALT increased 3.9-fold (2-fold at 100 km). Blood lactate and glucose
      levels did not change significantly. Hs-CRP increased 23-fold (3-fold at 100 km)
      and IL-6 increased 121-fold at 100 km, and then remained stable up to 200 km,
      whereas TNF- proportional, variant did not change significantly. Serum COMP
      increased 3-fold (1.3-fold at 100 km). Post-run CPK was correlated with LDH (r =
      0.62, P < 0.001), Hs-CRP (r = 0.45, P < 0.001), ALT (r = 0.89, P < 0.001), AST (r
      = 0.97, P < 0.001), and IL-6 (r = 0.61, P < 0.001). The present study
      demonstrated that blood biomarkers related to muscle and cartilage damage and
      inflammation were increased during a 200 km run and that this was particularly
      marked during the second half of the event. Ultra-marathon running clearly has a
      major impact on muscle and cartilage structures.

PMID- 17206444
TI  - Correction of compliance and resistance altered by endotracheal tube leaks and
      non-linear pressure/volume-relationships.
AB  - Measurements of lung compliance (C) and resistance (R) are influenced by
      endotracheal tube leaks (ETTL) as well as non-linear pressure/volume
      relationships (P/V relationship). To keep C and R reliable, we developed an
      algorithm to mathematically correct inspiratory and expiratory volume (V) and
      flow. In this study, a ventilated lung model for non-linear P/V relationship with
      adjustment of an increasing ETTL was studied. In addition, the recordings (airway
      pressure, flow, and volume) of 21 infants (median weight: 1,220 g, range: 640
      2,160 g, with a median leak size of 32%, range: 24-56%) were investigated. C and
      R were calculated continuously from the recordings of flow, volume, and airway
      pressure over time according to the changing volume. A method especially
      developed for the analysis of non-linear pressure-volume-relationship (APVNL) was
      employed. C and R affected by leaks were corrected applying the newly developed
      mathematical algorithm and compared with measurements without leakage. C could be
      corrected up to a leak of 80% and R up to 55% leak at half tidal V for the model
      with non-linear P/V-R. C and R without leak and after leak correction did not
      differ significantly in all infants where the APVNL method was applied (P >
      0.05).

PMID- 17206445
TI  - Generation and modulation of chemosensory behaviors in C. elegans.
AB  - C. elegans recognizes and discriminates among hundreds of chemical cues using a
      relatively compact chemosensory nervous system. Chemosensory behaviors are also
      modulated by prior experience and contextual cues. Because of the facile genetics
      and genomics possible in this organism, C. elegans provides an excellent system
      in which to explore the generation of chemosensory behaviors from the level of a
      single gene to the motor output. This review summarizes the current knowledge on
      the molecular and neuronal substrates of chemosensory behaviors and chemosensory
      behavioral plasticity in C. elegans.

PMID- 17206447
TI  - Angiotensin type 1 (AT1) and type 2 (AT2) receptors mediate the increase in TGF
      beta1 in thyroid hormone-induced cardiac hypertrophy.
AB  - Increased thyroid hormone (TH) levels are known to induce cardiac hypertrophy.
      Some studies have provided evidence for a functional link between angiotensin II
      (ANG II) and transforming growth factor beta1 (TGF-beta1) in the heart, both
      being able to also induce cardiac hypertrophy. However, the contribution of this
      growth factor activated directly by TH or indirectly by ANG II in cardiac
      hypertrophy development remains unknown. To analyze the possible role of TGF
      beta1 in cardiac hypertrophy induced by TH and also to evaluate if the TGF-beta1
      effect is mediated by ANG II receptors, we employed Wistar rats separated into
      control, hypothyroid (hypo) and hyperthyroid (T4 - 10) groups combined or not
      with ANG II receptor blockers (losartan or PD123319). Serum levels of T3 and T4,
      systolic pressure and heart rate confirmed the thyroid state of the groups. The
      T4 - 10 group presented a significant increase in cardiac TGF-beta1 levels;
      however, TGF-beta1 levels in the hypo group did not change in relation to the
      control. Inhibition of the increase in cardiac TGF-beta1 levels was observed in
      the groups treated with T4 in association with losartan or PD123319 when compared
      to the T4 - 10 group. These results demonstrate for the first time the TH
      modulated induction of cardiac TGF-beta1 in cardiac hypertrophy, and that this
      effect is mediated by ANG II receptors.

PMID- 17206446
TI  - Hyperosmotic stress response: comparison with other cellular stresses.
AB  - Cellular responses induced by stress are essential for the survival of cells
      under adverse conditions. These responses, resulting in cell adaptation to the
      stress, are accomplished by a variety of processes at the molecular level. After
      an alteration in homeostatic conditions, intracellular signalling processes link
      the sensing mechanism to adaptive or compensatory changes in gene expression. The
      ability of cells to adapt to hyperosmotic stress involves early responses in
      which ions move across cell membranes and late responses characterized by
      increased synthesis of either membrane transporters essential for uptake of
      organic osmolytes or of enzymes involved in their synthesis. The goal of these
      responses is to return the cell to its normal size and maintain cellular
      homeostasis. The enhanced synthesis of molecular chaperones, such as heat shock
      proteins, is another important component of the adaptive process that contributes
      to cell survival. Some responses are common to different stresses, whereas others
      are specific. In the first part of the review, we illustrate the characteristic
      and specific features of adaptive response to hypertonicity; we then describe
      similarities to and differences from other cellular stresses, such as genotoxic
      agents, nutrient starvation and heat shock.

PMID- 17206448
TI  - Measurements of membrane patch capacitance using a software-based lock-in system.
AB  - On-cell patch-clamp capacitance measurements can resolve the fusion of individual
      vesicles to a membrane patch and the accompanying dilation of the fusion pore. So
      far, these measurements have used a patch-clamp amplifier in combination with a
      hardware lock-in amplifier. Usually, solely the capacitance and conductance
      outputs of hardware lock-in amplifiers were recorded, which needed to be filtered
      rather heavily to suppress spectral components at the stimulus frequency.
      Therefore, the temporal resolution was limited, and information carried in the
      patch current was not utilized. In this paper, we describe an alternative and
      more versatile approach for measuring patch capacitance and conductance, using a
      digitally controlled patch-clamp amplifier. The software lock-in system showed
      better bandwidth and identical signal-to-noise performance needing less
      instrumentation. High temporal resolution measurements on patches of chromaffin
      cells showed that vesicle fission can be completed in only tens of microseconds.
      Capacitance calculation based on the patch current allows for straightforward
      offline phase correction. Moreover, the close inspection of direct current for
      the first time revealed small current changes accompanying the fusion and fission
      of large secretory vesicles, promising new insights into the vesicles' membrane
      properties. A practical guide to high-resolution on-cell patch-clamp capacitance
      measurements using the software lock-in is provided.

PMID- 17206450
TI  - Attentional demand and memory retrieval in negative priming.
AB  - Negative priming refers to delayed response to previous distractors, and can
      reflect the operation of attentional selection in prime trials. One important
      feature of negative priming is that it is modulated by the characteristics of
      probe trials. The current study manipulated competition from probe distractors
      and prime-probe similarity to examine the effects of attentional demand and
      memory retrieval in probe trials. The results demonstrated that the effects of
      attentional demand and memory retrieval on negative priming were dynamic.
      Distractor competition in probe trials affected negative priming in Experiment 1,
      and prime-probe similarity affected negative priming in Experiment 2. Moreover,
      negative priming in Experiment 3 was observed either when competition from probe
      distractors was strong or when identical spatial layouts were used in prime-probe
      couplets. Taken together, either competition from probe distractors or prime
      probe similarity of spatial layouts was critical to the manifestation of negative
      priming at one time. Implications for distractor inhibition and memory retrieval
      in negative priming were discussed.

PMID- 17206449
TI  - K+ channels stimulated by glucose: a new energy-sensing pathway.
AB  - Insights into how sugar can turn off cell activity are emerging from studies of
      hypothalamic neurons. Brain states are coordinated by hypothalamic
      orexin/hypocretin neurons, whose loss leads to narcoleptic instability of
      consciousness and inability to rouse when hungry. Recent studies indicate that
      glucose blocks the electrical activity of orexin cells by opening K+ channels in
      their membrane. This new energy-sensing mechanism is so sensitive that even small
      changes in glucose levels, of the type occurring between meals, can turn orexin
      cells on and off. Glucose-stimulated K+ channels share biophysical properties
      with "leak" (two-pore domain) K+ channels, the newest and least understood K+
      channel family. A hypothesis is outlined whereby the stimulation of brain K+
      channels by sugar could relieve stress and enhance reward, although probably at a
      cost of increased sleepiness.

PMID- 17206451
TI  - The xbp-1 gene is essential for development in Drosophila.
AB  - We report in this paper the characterization of Dxbp-1, the Drosophila homologue
      of the xpb-1 gene that encodes a "bZIP"-containing transcription factor that
      plays a key role in the unfolded protein response (UPR), an evolutionarily
      conserved signalling pathway activated by an overload of misfolded proteins in
      the endoplasmic reticulum (ER). Dxbp-1 is ubiquitously transcribed, and high
      levels are found in embryonic salivary glands and in the ovarian follicle cells
      committed to the synthesis of the respiratory appendages. Loss of function of
      Dxbp-1 induced a recessive larval lethality, thus, revealing an essential
      requirement for this gene. The Dxbp-1 transcript was submitted to an
      "unconventional" splicing that generated a processed Dxbp-1s transcript encoding
      a DXbp-1 protein isoform, as is the case for yeast, Caenorhabditis elegans and
      vertebrate hac1/xbp-1 transcripts after UPR activation. However, in the absence
      of exogenously induced ER stress, the Dxbp-1s transcript was also detectable not
      only throughout embryonic and larval development but also in adults with a high
      level of accumulation in the male sexual apparatus and, to a lesser extent, in
      the salivary glands of the third-instar larvae. Using a Dxbp-1:GFP transgene as
      an in vivo reporter for Dxbp-1 mRNA unconventional splicing, we confirmed that
      Dxbp-1 processing took place in the salivary glands of the third-instar larvae.
      The Dxbp-1 gene appears, thus, to play an essential role during the development
      of Drosophila, hypothetically by stimulating the folding capacities of the ER in
      cells committed to intense secretory activities.

PMID- 17206453
TI  - Autoimmune sclerosing cholangitis in two sisters.

PMID- 17206452
TI  - Peptidomic analysis of human peripheral monocytes persistently infected by
      Chlamydia trachomatis.
AB  - Peptidomic analysis using Differential Peptide Display (DPD) of human peripheral
      blood mononuclear cells (PBMC) mock-infected or persistently infected by
      Chlamydia trachomatis (CT) revealed 10 peptides, expressed upon CT infection.
      Analysis of these 10 candidates by tandem mass spectrometry enabled the
      determination of seven candidates as fragments from the precursors (I) ferritin
      heavy chain subunit, (II) HLA class II histocompatibility antigen, (III)
      vimentin, (IV) indoleamine 2,3-dioxygenase, (V and VI) pre-B cell enhancing
      factor (PBEF), and (VII) Interleukin-8 (CXCL8). The identified candidates proved
      the presence of anti-bacterial and immunologically active monocytic proteins
      after CT infection.

PMID- 17206454
TI  - Stevens-Johnson syndrome.

PMID- 17206455
TI  - Improvements of hypertriglyceridemia and hyperlacticemia in Japanese children
      with glycogen storage disease type Ia by medium-chain triglyceride milk.
AB  - BACKGROUND: Besides profound hypoglycemia with hyperlacticemia, glycogen storage
      disease type Ia (GSD Ia) presents hypertriglyceridemia that is often resistant to
      dietary treatment with cornstarch. The present study aimed to evaluate the
      effects of medium-chain triglycerides (MCT)--which are absorbed via the portal
      vein without being incorporated into chylomicrons--on hypertriglyceridemia and to
      explore otherwise metabolic changes in children with GSD Ia. PATIENTS AND
      METHODS: A 13-year-old boy with GSD Ia who received a dietary treatment with MCT
      milk after cornstarch administration and two infants also with GSD Ia, ages 6 and
      7 months, who received MCT milk after carbohydrate-rich, lipid-poor milk were
      enrolled. In addition to serum glucose and lactate levels, serum levels of total
      cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol were
      serially determined. Simultaneously, serum levels of total carnitine, free
      carnitine, acylcarnitine, and ketone bodies were determined to evaluate fatty
      acid beta-oxidation. RESULTS: Mean glucose level (mmol/l) of patient 1 remained
      stable, the value being around 4.5, while those of patients 2 and 3 increased to
      this level from 4.00 and 3.72, respectively. Lactate levels were significantly
      decreased in all patients. Mean triglyceride levels (mM) of patient 1 decreased
      from 3.00 to 2.05. Also, triglyceride levels of patients 2 and 3 decreased from
      2.74 and 3.15 to 2.13 and 2.70, respectively. HDL cholesterol, acylcarnitine, and
      ketone body levels increased in all patients after MCT administration, while
      total and free carnitine levels decreased. CONCLUSION: We describe here the
      beneficial effects on lipid and carbohydrate metabolisms in three Japanese
      children with GSD Ia. In light of the unfavorable influence of lipid restriction
      on growth and development in infancy, dietary treatment with MCT milk may be a
      better treatment for infants with GSD Ia. Further investigation should be
      required to confirm the efficacy of MCT milk in GSD Ia.

PMID- 17206456
TI  - A newborn with VLCAD deficiency. Clinical, biochemical, and histopathological
      findings.
AB  - Here we report a newborn with VLCAD deficiency with a severe neonatal onset type
      who presented with hypoglycemia, cardiomyopathy, mild hepatomegaly and slight
      hypoalbuminemia. The patient was also homozygous for a new missense mutation
      (R456H). Postmortem examination of the liver, heart and skeletal muscle revealed
      diffuse lipid accumulation in various amounts. Mild lobular and portal fibrosis
      as well as severe macrovesicular steatosis were also found in the liver. The
      fatal course of the patient may have resulted from diffuse lipid accumulation in
      the liver and myocardium, which probably began during the intrauterine life with
      slight hypoalbuminemia as a silent marker of this process.

PMID- 17206459
TI  - A comparison of myocardial perfusion and rejection in cardiac transplant
      patients.
AB  - INTRODUCTION: Although histological evaluation of the cardiac tissue is the
      current gold standard for evaluation of rejection, we hypothesized that cardiac
      perfusion MRI is a safe non-invasive method that correlates tissue blood flow
      changes with biopsy proven rejection in the cardiac transplant patient. MATERIALS
      AND METHODS: In a retrospective study from 1984-2001, 83 patients underwent 135
      MR Gd-DTPA imaging studies. In 8 patients (9%), biopsies graded 2 or higher (by
      ISHLT criteria) provided evidence of rejection. Patients were age and sex matched
      to 11 non-rejected controls for imaging analysis. Time-signal intensity curves
      generated for a mid-ventricle LV short axis slice during rest and adenosine
      stress allowed determination of myocardial blood flow (MBF, ml/min/gm). ROC curve
      analysis by SPSS allowed estimation of sensitivity and specificity. RESULTS: At
      rest, there was no difference in MBF between patients with prior rejection vs.
      those without (1.18 +/- 0.26 vs. 1.16 +/- 0.29). At stress there was a decrease
      in MBF for patients with prior rejection episodes (3.27 +/- 0.74) compared to no
      rejection (3.60 +/- 0.72), P = 0.067). The area under the ROC curve was 0.82,
      with specificity and sensitivity of 75% and 81%, respectively. CONCLUSION: This
      study suggests that perfusion MR imaging can be used in assessing the cardiac
      transplant patient for rejection related microvascular changes. The high
      specificity and sensitivity recorded from the ROC curve illustrates the potential
      utility of this diagnostic test for future studies.

PMID- 17206460
TI  - Metals and radionuclides in birds and eggs from Amchitka and Kiska Islands in the
      Bering Sea/Pacific Ocean ecosystem.
AB  - Metals and radionuclide levels in marine birds of the Aleutians are of interest
      because they are part of subsistence diets of the Aleut people, and can also
      serve as indicators of marine pollution. We examined geographic and species
      specific variations in concentrations of radionuclides in birds and their eggs
      from Amchitka, the site of underground nuclear tests from 1965 to 1971, and Kiska
      Islands (a reference site) in the Aleutians, and the levels of lead, mercury and
      cadmium in eggs. In 2004 we collected common eiders (Somateria mollissima),
      tufted puffins (Fratercula cirrhata), pigeon guillemot (Cepphus columba) and
      glaucous-winged gulls (Larus glaucescens) from Amchitka and Kiska, and eggs from
      eiders and gulls from the two island. We also collected one runt bald eagle
      (Haliaeetus leucocephalus) chick from both Amchitka and Kiska Islands. For most
      species, the levels of radionuclide isotopes were below the minimum detectable
      activity levels (MDA). Out of 74 cesium-137 analyses, only one composite (gulls)
      was above the MDA, and out of 14 composites tested for plutonium (Pu-239, 240),
      only one exceeded the MDA (a guillemots). Three composites out of 14 tested had
      detectable uranium-238. In all cases, the levels were low and close to the MDAs,
      and were below those reported for other seabirds. There were significant
      interspecific differences in metal levels in eggs: gulls had significantly higher
      levels of cadmium and mercury than the eiders, and eiders had higher levels of
      lead than gulls. There were few significant differences as a function of island,
      but eiders had significantly higher levels of cadmium in eggs from Kiska, and
      gulls had significantly higher levels of mercury on Kiska. The levels of cadmium
      and mercury in eggs of eiders and gulls from this study were above the median for
      cadmium and mercury from studies in the literature. The levels of mercury in eggs
      are within the range known to affect avian predators, but seabirds seem less
      vulnerable to mercury than other birds. However, the levels of mercury are within
      the action levels for humans, suggesting some cause for concern if subsistence
      Aleuts eat a large quantity of eggs.

PMID- 17206461
TI  - Banding patterns and chromosomal evolution in five species of neotropical Teiinae
      lizards (Squamata: Teiidae).
AB  - Karyotypes of five species of South American teiid lizards from subfamily
      Teiinae: Ameiva ameiva, Kentropyx calcarata, K. paulensis, K. vanzoi (2n = 50,
      all acrocentric), and Cnemidophorus ocellifer (2n = 50, all biarmed), are herein
      described and compared on the basis of conventional and silver staining, and CBG
      and RBG banding patterns. Meiotic data are also included. Karyotypes of K.
      paulensis, K. vanzoi, and C. ocellifer are reported here for the first time.
      Inter-generic variability in Ag-NORs location was detected with NORs occurring at
      the end of long arm of pair 1 in K. calcarata, K. paulensis, and K. vanzoi; pair
      5 in C. ocellifer and pair 7 in A. ameiva. The location of NORs, along with the
      karyological differences between A. ameiva and the Central American species (A.
      auberi), corroboretes the molecular-based hypothesis that the genus Ameiva is
      paraphyletic. Inter-populational heteromorphism in Ag-NORs size was detected
      between populations of C. ocellifer. RBG and CBG banding data demonstrated that
      the biarmed condition of the C. ocellifer chromosomes is due to multiple
      pericentric inversion events instead of addition of constitutive heterochromatin.
      Differential-staining techniques used here revealed valuable information about
      Teiinae karyotypic diversity and made it possible to compare these species,
      contributing to both the better comprehension of their chromosomal evolution and
      issues on taxa systematics.

PMID- 17206463
TI  - Progressive retinal dystrophy in two sisters with glutathione synthetase (GS)
      deficiency.
AB  - We report the ophthalmological findings of two sisters with severe glutathione
      synthetase deficiency, an autosomal recessive inborn error of metabolism
      resulting in very low intracellular levels of the free-radical scavenger
      glutathione. The patients were investigated because of declining visual acuity.
      The most prominent finding was progressive retinal dystrophy with
      hyperpigmentations and maculopathy. Generally disturbed functioning of both the
      outer and inner layers of the retina resulted in attenuated or nearly abolished
      electroretinograms. These findings agree with a rod/cone type of retinal
      dystrophy, and we suggest that this is due to glutathione deficiency. Treatment
      with antioxidants such as vitamins E and C seems to prevent the progression of
      CNS damage. We speculate that it might also prevent retinal dystrophy in patients
      with glutathione synthetase deficiency. We suggest that patients with retinal
      dystrophy and additional neurological signs should be investigated for a defect
      in glutathione metabolism. Also, we recommend that patients with low levels of
      glutathione should be examined for retinal dystrophy. Our results suggest that a
      decreased capacity for scavenging reactive oxygen species and/or increased
      oxidative stress may cause retinal dystrophy. If this is the case, the redox
      state in the retina should be a potentially useful therapeutic target to prevent
      reduced visual function and blindness.

PMID- 17206462
TI  - The Dutch Fabry cohort: diversity of clinical manifestations and Gb3 levels.
AB  - BACKGROUND: Fabry disease (OMIM 301500) is an X-linked lysosomal storage disorder
      with characteristic vascular, renal, cardiac and cerebral complications.
      Globotriaosylceramide (Gb(3)) accumulates in Fabry patients as a result of alpha
      galactosidase A deficiency. The phenotypic variability is high, but the
      relationship between clinical symptoms in individual Fabry patients has not been
      uniformly documented. Also, the relation between the most prominent biochemical
      abnormalities, elevated Gb(3) levels in plasma and urine, and clinical symptoms
      is not firmly established. METHODS: Clinical and biochemical characteristics of
      96 (25 deceased) Dutch Fabry patients were collected retrospectively and before
      the initiation of enzyme therapy. RESULTS: Clinical assessment revealed that
      median life expectancy was 57 years for male and 72 years for female patients.
      Cerebral complications, acroparaesthesias and gastrointestinal complications, but
      not cardiac and auditory complications, were all seen more frequently in male
      than female patients. Glomerular filtration rate (GFR) was highly variable in
      male patients, including 2 patients with GFR < 30 ml/min, but median GFR did not
      differ between males and females (103 and 101 ml/min, respectively).
      Hyperfiltration was more frequently observed in the female patient group.
      Microalbuminuria was present in 60% of males and 45% of females. No specific
      pattern of combined symptoms existed except for a relationship between left
      ventricular hypertrophy (LVH) and cerebral complications (males 36%, females
      32%), or proteinuria (males 35%, females 31%). Gb(3) was found to be more
      elevated in plasma samples from male (n = 26; median 6.27 micromol/L (1.39-9.74))
      than female Fabry patients (n = 37; median 2.16 (0.77-4.18)). This was also
      observed for urinary Gb(3): males (n = 22) median 1851 nmol/24 h (40-3724);
      females (n = 29) median 672 (86-2052). Plasma and urinary Gb(3) levels correlated
      with each other in both males (r = 0.4, p = 0.05) and females (r = 0.4, p =
      0.03), but no correlation between elevated Gb(3) levels and clinical symptoms
      could be detected. CONCLUSION: Analysis of the characteristics of the Dutch Fabry
      cohort has revealed that a limited relationship between various disease
      manifestations exists and that individual symptoms do not correlate with elevated
      urinary or plasma Gb(3) levels, limiting their value as surrogate disease
      markers.

PMID- 17206464
TI  - A new technique for assaying cytochrome P450 enzyme activity in a single cell.
AB  - A new microspectrofluorometric technique for measuring the ethoxyresorufin-O
      deethylase (EROD) activity of cytochrome P450 (CYP)1A1 in single living cells is
      described. The system, which uses a perfusion chamber and an HPLC pump, allowed
      cells to be stained, fixed, blocked, and washed by injecting each treatment
      solution into the on-line carrier stream of buffer from the sampling block of the
      HPLC pump. After addition of the substrate 7-ethoxyresorufin, the fluorescence
      intensity of the metabolite resorufin was measured in individual cells.
      Fluorescence intensity steeply increased to a unique peak for each cell and then
      decreased to the basal level. Furthermore, CYP1A1 in each cell was stained with
      its antibody and quantified using the fluorescence intensity of an FITC
      conjugated secondary antibody. EROD activity was normalized using the FITC
      fluorescence. The results show that the initial slopes and peak values of
      resorufin production by the cells were dependent on the CYP1A1 level. Treatment
      of hepatocytes with two nonspecific P450 inhibitors, cimetidine and SKF-525A,
      suppressed EROD activity.

PMID- 17206465
TI  - The role of biomedical knowledge in diagnosis of difficult clinical cases.
AB  - Although biomedical knowledge is believed to be of little value in diagnosis of
      routine clinical cases, studies of clinical reasoning have found that physicians
      revert to use of basic biomedical knowledge when faced with challenging clinical
      problems. The current paper presents two experiments that empirically examine the
      role of biomedical knowledge in diagnosis of difficult cases by novice
      diagnosticians. Novices are taught to diagnose a series of artificial diseases
      using either knowledge of causal mechanisms or a list of clinical features. In
      Experiment 1, participants are then tested on two types of clinical challenges:
      (1) case summaries with irrelevant findings; (2) cases using unfamiliar
      terminology. Participants with an understanding of underlying mechanisms out
      performed their counterparts on both types of cases. In Experiment 2,
      participants are tested 1 week after initial training. Participants with
      knowledge of causal mechanisms were found to do better on cases with unfamiliar
      terminology. The results of the two studies provide additional support for the
      critical role of biomedical knowledge in diagnosis of difficult clinical cases.

PMID- 17206466
TI  - Sexual history inquiry and HIV counseling: improving clinical skills and medical
      knowledge through an interactive workshop utilizing standardized patients.
AB  - BACKGROUND: Sexual history and HIV counseling (SHHIVC) are essential clinical
      skills. Our project's purpose was to evaluate a standardized patient educational
      intervention teaching third-year medical students SHHIVC. METHODS: A four-hour
      standardized patient workshop was delivered to one-half of the class each of
      three consecutive years at one medical school. Approximately 3.5 weeks later, all
      students engaged in a standardized patient examination including one station
      assessing SHHIVC, answered an open-ended written exercise following the
      standardized patient encounter, and completed a written examination including
      sexual history and HIV-related questions. RESULTS: Workshop participants scored
      higher than non-participants on SHHIVC items on the standardized patient station
      (P < .0001), written exam (P < .0001), and open-ended written exercise after the
      standardized patient encounter (P = .024). CONCLUSIONS: Our SHHIVC curriculum was
      associated with students demonstrating better clinical skills on a SHHIVC
      standardized patient examination station and more SHHIVC knowledge on two
      measures of medical knowledge than students not participating in the SHHIVC
      educational intervention.

PMID- 17206467
TI  - Optimizing the design of web-based questionnaires--experience from a population
      based study among 50,000 women.
AB  - BACKGROUND: Web-questionnaires are an important tool for future epidemiological
      research because these allow for rapid and cost-efficient assembly of self
      reported information on risk factors and health outcomes. However, to achieve
      high response rates it is essential to accommodate factors that prevent drop out
      and so insure validity of future studies. We aim to study how socio-demographic
      variables as well as design issues such as the ordering and level of difficulty
      (Easy-to-hard vs. Hard-to-easy) of questions in a web-questionnaire affects the
      probability of drop out and non-response. METHOD: In 2003 we invited 47,859 women
      participating in an ongoing prospective study to a follow-up using a web-based
      mode. Two versions of the questionnaire existed, varying in level of difficulty
      (Easy-to-hard vs. Hard-to-easy). We report drop out (proportion non-completers)
      between groups defined by level of difficulty and estimated adjusted risk
      differences. RESULTS: The drop out differs significantly depending on the order
      of the questions in the web-questionnaire. The socio-demographic pattern among
      lurkers (participants that enter, start responding to, but do not complete a web
      questionnaire) differs from that among completers of web-questionnaires.
      CONCLUSIONS: An additional 6% units of completers--persons initiating and
      completing the questionnaire--can be obtained by considering the ordering of
      questions. A group uniquely identified in web-surveys, as lurkers are potentially
      easier to persuade to complete an already started web-questionnaire compared to a
      non-responder. Lurkers thus constitute a unique opportunity of decreasing the
      drop out rate and therefore merit future research.

PMID- 17206468
TI  - NMR resonance assignments of the human high mobility group protein HMGA1.

PMID- 17206469
TI  - Backbone and side chain 1H, 13C, and 15N resonance assignments of AF2241 from
      Archaeoglobus fulgidus.

PMID- 17206470
TI  - Complete 1H, 13C and 15N resonance assignments of Blo t 5, a major mite allergen
      from Blomia tropicalis.

PMID- 17206471
TI  - The transduction of His-TAT-p53 fusion protein into the human osteogenic sarcoma
      cell line (Saos-2) and its influence on cell cycle arrest and apoptosis.
AB  - The p53 gene is a tumor suppressor gene. It encodes a nuclear phosphoprotein p53
      involved in the regulation of cell cycle arrest and apoptosis to maintain the
      genomic integrity of the cell. As mutations of p53 gene are found in most human
      cancers, p53 protein becomes a hot target in the research of anticancer therapy.
      In the present study, an 11-amino acid domain of TAT protein which has been
      demonstrated to be able to transduce across cell membranes was fused with p53.
      The result revealed that the fusion protein His-TAT-p53 accumulated in the
      nucleus and inhibited the growth of the Saos-2 cells. Besides apoptosis, an
      increased percentage of G2 phase suggested that the transduction of His-TAT-p53
      into cells might be associated with a G2 arrest of cell cycle.

PMID- 17206472
TI  - Down-regulation of Wilms' tumor 1 expression in glioblastoma cells increases
      radiosensitivity independently of p53.
AB  - The Wilms' tumor 1 (WT1) gene is overexpressed in human glioblastoma and
      correlates with wild-type p53 status. In other cell types, WT1 inhibits p53
      mediated apoptosis in response to DNA damaging agents. However, neither this
      interaction nor the relationship between WT1 and radiosensitivity has been
      studied in glioblastoma. To study this interaction, we generated LN-229 glioma
      cell lines (p53 mutant) stably expressing WT1 isoforms and induced apoptosis by
      transfecting with different doses of wild-type p53 plasmid expression vector.
      Constitutive expression of WT1 did not protect against exogenous p53-mediated
      apoptosis. Likewise, WT1 expression did not protect against endogenous p53
      mediated cell death induced by radiotherapy in U87MG cells, which contain
      functional wild-type p53. We then tested the efficacy of WT1 siRNA in inhibiting
      WT1 expression and its effect on radiosensitivity. In T98G and LN-18 glioma
      cells, which possess p53 mutations, WT1 siRNA decreased WT1 protein to almost
      undetectable levels by 96-h post-transfection. Furthermore, WT1 siRNA
      transfection caused a significantly larger decrease in viability following
      irradiation than was seen in untransfected cells in both cell lines after
      treatment with ED50 of ionizing radiation. In conclusion, WT1 overexpression did
      not protect against p53-mediated apoptosis or ionizing radiation induced cell
      death. WT1 siRNA increased the radiosensitivity of two human glioma cell lines
      independently of p53. Anti-WT1 strategies may, therefore, prove useful in
      improving the response of glioblastoma to radiotherapy, thus potentially
      improving patient survival.

PMID- 17206473
TI  - Radiation induced peripheral nerve tumors: case series and review of the
      literature.
AB  - PURPOSE: Radiation induced peripheral nerve tumors (PNT) are a rare but known
      complication of radiotherapy. The clinical and pathologic features of six cases
      of post-radiation PNT's are reported here, more than doubling the number of known
      cases reported in the literature. METHODS: We reviewed six cases of radiation
      induced PNT and performed a review of the current literature on radiation induced
      neurofibromas. RESULTS: Patient's ranged in age from 18 months to 49 years at the
      time of their original diagnosis, with radiation doses to the primary tumor
      ranging from 24 to 40 Gy with post radiation intervals from 10 to 50 years. The
      majority of PNT's identified were neurofibromas (3) and schwannomas (3). Nuclear
      atypia, S100 positive staining and mild-moderate cellularity were common
      pathologic findings. CONCLUSIONS: There are only a handful of neurofibromas in
      the 60 cases of PNT's thus far reported. This case series broadens the post
      radiation neurofibroma literature. While the pathology of PNT induced
      transformation is still poorly understood, experiments and pathology are
      congruent on the possibility of malignant transformation, especially for the
      "atypical neurofibroma". On the clinical level, this case series lends its
      support to some, but not all, of the risk factors thought to predispose to the
      formation of radiation induced neurofibromas. Though rare, the complication of
      radiation-induced neurofibroma cannot be ignored, especially with the increasing
      use of focused radiosurgical techniques.

PMID- 17206474
TI  - Long term outcome with post-operative radiation therapy for spinal canal
      ependymoma.
AB  - PURPOSE: A retrospective study was performed to evaluate the long term efficacy
      and safety of post-operative radiation therapy in the management of spinal canal
      ependymoma at our institution. METHODS AND MATERIALS: Between 1954 and 1997, 22
      patients with spinal canal ependymoma were treated with post-operative
      radiotherapy at our institution. The median age at diagnosis was 34.7 years
      (range 9.8-56.1 years). All patients underwent open biopsy with histologic
      diagnosis: 13 patients (59%) had ependymoma (WHO Grade II) and 9 patients (41%)
      had myxopapillary ependymoma (WHO Grade I). The median tumor size was 4.0 cm
      (range 1.5-15.0 cm). Twenty patients received subtotal resection and 2 patients
      received gross-total resection. Median radiation dose was 45.0 Gy. RESULTS: The
      median follow up for surviving patients was 11.4 years (range 0.6-37.0 years). An
      80% progression-free-survival (PFS) was observed for all patients at 5-, 10- and
      15-year endpoints. All recurrences were within 3 years of treatment. The 5-, 10-
      and 15-year overall-survivals (OS) for all patients were 85%, 78% and 64%,
      respectively. Patients with tumors larger than 6.0 cm at time of presentation
      demonstrated 5- and 10-year PFS of 58.3% compared to 92.3% for patients with
      tumors 6.0 cm or smaller (P = 0.047). There was no significant correlation
      between tumor size and OS. CONCLUSIONS: Post-operative radiation after subtotal
      resection is safe and offers durable tumor control and long term patient
      survival.

PMID- 17206476
TI  - The importance of early postoperative radiation in spinal myxopapillary
      ependymomas.

PMID- 17206475
TI  - Frequent but borderline methylation of p16 (INK4a) and TIMP3 in medulloblastoma
      and sPNET revealed by quantitative analyses.
AB  - Certain risk groups among tumors of the central nervous system (CNS) in children
      take an almost inevitably fatal course. The elucidation of molecular mechanisms
      offers hope for improved therapy. Aberrant methylation is common in malignant
      brain tumors of childhood and may have implications for stratification and
      therapy. Methylation of p16 (INK4A), p14 (ARF), TIMP3, CDH1, p15 (INK4B )and
      DAPK1 in medulloblastoma (MB) and ependymoma has been discussed controversially
      in the literature. DUTT1 and SOCS1 have not previously been analyzed. We examined
      methylation in MB, sPNET and ependymoma using methylation-specific PCR (MSP),
      quantitative Combined Bisulfite Restriction Analysis (COBRA) and direct and clone
      sequencing of bisulfite PCR products. We detected methylation of p16 (INK4A)
      (17/43), p14 (ARF) (11/42) and TIMP3 (9/44) in MB and others by MSP. CDH1 was not
      only methylated in MB (31/41), but also in normal controls. Evaluation of MSP
      results by quantitative COBRA and sequencing yielded methylation between the
      detection limits of COBRA (1%) and MSP (0.1%). Only p16 (INK4A )and TIMP3 were
      methylated consistently in medulloblastomas (p16 (INK4A ) 14%, TIMP3 11%) and p16
      (INK4A) also in anaplastic ependymomas (1/4 tumors). Methylation ranged from 1
      5%. Evaluation of methylation using MSP has thus to be supplemented by
      quantitative methods. Our analyses raise the issue of the functional significance
      of low level methylation, which may disturb the delicate growth factor
      equilibrium within the cell. Therapeutic and diagnostic implications urge into
      depth analyses of methylation as a mechanism, which might fill some of the gaps
      of our understanding of brain tumor origin.

PMID- 17206477
TI  - Short-term exposure of cancer cells to micromolar doses of paclitaxel, with or
      without hyperthermia, induces long-term inhibition of cell proliferation and cell
      death in vitro.
AB  - BACKGROUND: During intraoperative hyperthermic intraperitoneal chemotherapy for
      primary or secondary peritoneal malignancies, tumor cells are exposed to high
      drug concentrations for a relatively short period of time. We investigated in
      vitro the effect of paclitaxel and hyperthermia on cell proliferation, cell cycle
      kinetics and cell death under conditions resembling those during intraoperative
      hyperthermic intraperitoneal chemotherapy. METHODS: Human breast MCF-7, ovarian
      SKOV-3 and hepatocarcinoma HEpG2 cells were exposed to 10 and 20 microM
      paclitaxel at 37, 41.5 or 43 degrees C for 2 h. Cell proliferation, cell cycle
      kinetics, necrosis and apoptosis were evaluated. RESULTS: Hyperthermia exerted a
      cytostatic effect to all cell lines and at 43 degrees C a cytotoxic effect on MCF
      7 cells. MCF-7 and SKOV-3 cells treated under normothermic conditions with
      paclitaxel were arrested at G2/M or M phase for at least 3 days. Most of MCF-7
      cells and approximately half of SKOV-3 cells were in interphase and became
      multinucleated without properly completing cytokinesis. Hyperthermia at 41.5
      degrees C altered cell cycle distribution and affected the paclitaxel-related
      effect on cell cycle kinetics of MCF-7 and SKOV-3 cells. Analysis of the mode of
      cell death showed that cell necrosis prevailed over apoptosis. Hyperthermia at 43
      degrees C increased paclitaxel-mediated cytotoxicity in MCF-7 cells and to a
      lesser extent in SKOV-3 and HEpG2 cells. CONCLUSIONS: Short-time treatment of
      carcinoma cells with high (micromolar) concentrations of paclitaxel in
      normothermic and hyperthermic conditions is highly efficient for cell growth
      arrest and could be of clinical relevance in locoregional chemotherapy.

PMID- 17206478
TI  - Monitoring health outcomes following cytoreductive surgery plus intraperitoneal
      hyperthermic chemotherapy for peritoneal carcinomatosis.
AB  - BACKGROUND: Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy
      for peritoneal carcinomitosis (PC) is an aggressive treatment designed to
      alleviate symptoms and prolong life. It is associated with physical and
      psychological morbidity. The purpose of this study was to monitor health outcomes
      related to treatment. METHODS: Patients completed a questionnaire before and
      after surgery at 3, 6 and 12 months. The questionnaire consisted of basic
      demographic items as well as the Functional Assessment of Cancer Therapy-Colon
      Scale (FACT-C), SF-36 Medical Outcomes Study Health Survey, Center for
      Epidemiologic Studies-Depression Scale (CES-D), Brief Pain Inventory-Short Form,
      and ECOG Performance Status Rating. Time trends were assessed with mixed models
      (SAS PROC MIXED) so as to use all data and to account for missing data. RESULTS:
      Ninety-six patients (49% females, 9% African Americans) of an average age of 52.9
      (SD = 12.5) years were assessed before surgery. PC originated in primary lesions
      of the appendix (n = 36); colon/rectum (n = 24); mesothelium (n = 9); ovary (n =
      5); stomach (n = 4); and miscellaneous (n = 18). Quality of life (QOL) and pain
      scores improved from baseline to 12 months. Physical functioning changed over the
      12-month study period with improvement recorded at 6 months. The percentage of
      patients reporting significant depressive symptom at each time point was;
      baseline = 32%; 3 months = 19%; 6 & 12 months = 24%. CONCLUSIONS: Acceptable QOL,
      return of functional status, and reduced pain can be attained between 3 and 6
      months following treatment although some deficits in general health remain.
      Depressive symptoms are common and should be monitored.

PMID- 17206479
TI  - TAT-Bim induces extensive apoptosis in cancer cells.
AB  - BACKGROUND: Suppression of apoptosis is central to the development of cancer and
      is associated with resistance to modern adjuvant treatments. Therefore, molecules
      and pathways of apoptotic processes are critical targets for the development of
      anti-cancer therapeutics. Since apoptosis is executed by intracellular proteins,
      molecular approaches must incorporate a method to deliver the treatment into the
      tumor cells. METHODS: We utilized a peptide that contains two domains, a peptide
      transduction domain derived from the HIV-1 TAT protein and a biological effector
      domain, the BH3 domain from the pro-apoptotic Bcl-2 family member Bim. We
      examined whether this construct (TAT-Bim) induced apoptosis in several cancer
      cell lines (T-cell lymphoma (EL4), pancreatic cancer (Panc-02), and melanoma
      (B16)) and whether TAT-Bim treatment synergized with radiation. A mutant TAT-Bim
      peptide with no biologic activity (TAT-Bim-inactive) was used as a control.
      C57/BL6 mice were challenged with syngeneic cancer cell lines and the effects of
      intratumoral TAT-Bim injection on tumor growth and host survival were determined.
      RESULTS: TAT-Bim was internalized by all cancer cells within two hours. TAT-Bim
      resulted in apoptosis in a dose dependent fashion in all cell lines and sublethal
      irradiation augmented the effects of TAT-Bim induced apoptosis. TAT-Bim
      significantly slowed tumor growth in murine models of pancreatic cancer and
      melanoma. CONCLUSION: TAT-Bim exemplifies a strategy for cancer therapy that
      involves inducing apoptosis by antagonizing the endogenous anti-apoptotic
      machinery. Small peptide therapeutics, in combination with traditional adjuvant
      therapies such as radiation, may provide a valuable 'second hit' and drive tumor
      cells into programmed cell death.

PMID- 17206480
TI  - Peroneal neuropathy due to ground pad burn injury after a radiofrequency ablation
      surgery.

PMID- 17206481
TI  - Intra-operative touch preparation cytology; does it have a role in re-excision
      lumpectomy?
AB  - OBJECTIVE: Breast carcinoma is the most frequently diagnosed malignancy in women
      of North America. The combination of breast conservation surgery and radiotherapy
      has become a standard of treatment for the majority of breast cancers. It is
      critical to obtain clear margins to minimize local recurrence. However, avoiding
      multiple re-excisions for margin clearance helps optimize cosmetic results in
      patients undergoing breast conservation surgery. Intra-operative touch
      preparation cytology (IOTPC) may decrease the need for multiple re-excisions and
      thereby improve cosmesis. The literature suggests that IOTPC can be useful in
      evaluation of margins. Klimberg et al. evaluated the touch preparation technique
      prospectively in 428 patients undergoing breast biopsy for undiagnosed breast
      masses. Margin evaluation was correct in 100% of the lesions and was used to re
      excise the margins when touch prep results were positive. They reported a
      diagnostic accuracy, sensitivity, specificity, positive predictive value, and
      negative predictive value of 100% for the touch prep technique. To the best of
      our knowledge, there has been no published data on the role of IOTPC for
      evaluation of margins in re-excision cases. This report describes our experience
      with IOTPC for margin assessment for re-excision partial mastectomy at Beth
      Israel Medical Center (BIMC). The purpose of this study is to determine whether
      IOTPC is reliable for evaluating margins in patients undergoing re-excision for
      involved or close margins. METHODS: A prospective study of 30 patients, who have
      undergone re-excision partial mastectomy for involved or close margins after
      breast conservation surgery with the use of IOTPC for margin assessment at BIMC
      was performed. The re-excision lumpectomy specimens were oriented by the surgeon
      intra-operatively and were submitted fresh to pathology for cytologic assessment.
      The touch prep method consisted of touching the corresponding margin onto the
      glass slide. The principle of this technique is that if cancer cells are present
      they will stick to the slide, while fat cells will not. A slide was prepared for
      each re-excision specimen. Air-dried samples were stained immediately using the
      Diff-Quik method and examined under the microscope by a cytopathologist. RESULTS:
      Thirty patients underwent re-excision lumpectomy for involved or close margins
      with touch preparation cytology for assessment of 68 margins. Twenty-six patients
      had invasive ductal carcinoma and/or ductal carcinoma in situ, three patients had
      invasive lobular carcinoma and the remaining one patient had a combination of
      invasive lobular and ductal carcinoma. There was a correlation between touch prep
      cytology and final pathology in 56/68 margins, which accounts for 82.4% of the
      cases. CONCLUSION: Intra-operative touch preparation cytology for assessment of
      margins in patients undergoing re-excision lumpectomy for involved or close
      margins has a sensitivity of 75%, specificity of 82.8%, positive predictive value
      of 21.4%, and negative predictive value of 98.2%. This high negative predictive
      value and a single false negative margin are quite significant. Therefore, based
      on our experience, IOTPC can be a useful tool for intra-operative assessment of
      margins for patients undergoing re-excision partial mastectomy.

PMID- 17206482
TI  - Sentinel lymph node mapping in colon cancer: current status.
AB  - BACKGROUND: The primary role of sentinel lymph node (SLN) mapping in colon cancer
      is to increase the accuracy of nodal staging by identifying those lymph nodes
      with the greatest potential for harbouring metastatic disease. Ultrastaging
      techniques aim to identify the otherwise undetected metastases. Until now, no
      consensus exists as to the most optimal procedure in patients with colon cancer.
      METHODS: A systematic literature search on the value of different SLN mapping
      techniques in patients with colon cancer was performed using the electronic
      search engine PubMed. Prospective studies published before 1 December 2005 were
      included and further articles were selected by cross-referencing. The results of
      different techniques using either blue dye or radiocolloid, were investigated.
      RESULTS: The literature search yielded 17 relevant articles. SLN mapping using
      blue dye was described in 15 studies. Two studies reported the results of SLN
      mapping using a combination of blue dye and radiocolloid. The reported results on
      identification rate varied between 71 and 100%. Accuracy rates were between 78
      and 100%, sensitivity rates between 25 and 100% and true upstaging rates between
      0 and 26%. The results were not affected by the addition of radiocolloid to blue
      dye. CONCLUSIONS: Sentinel lymph node mapping in patients with colon cancer
      remains an experimental procedure with varying results. Further evaluation may
      lead to a standardized technique that offers the potential for significant
      upstaging of stage II patients. This may have important implications as to tailor
      adjuvant chemotherapeutic regimens in these patients.

PMID- 17206483
TI  - Retroperitoneal and truncal sarcomas: prognosis depends upon type not location.
AB  - BACKGROUND: Prognostication of truncal and retroperitoneal soft tissue sarcomas
      has traditionally been predicated on tumor location and grade. OBJECTIVE: To
      compare outcomes for patients with retroperitoneal or truncal sarcomas. METHODS:
      Retrospective analysis of a prospective cancer data registry from 1977 to 2004
      was performed and outcomes were determined. RESULTS: The study group numbered 312
      patients (median age 58 years, 54% male, 56% Caucasian, 14% black, 29% Hispanic).
      The most common tumor types were liposarcoma (35.9%), leiomyosarcoma (30.1%), and
      malignant fibrous histiocytoma (MFH) (19.5%). Tumor distributions were
      retroperitoneal (38.9%), pelvic (24.7%), abdominal (18.6%) and thoracic (17.9%).
      Median overall survival was 74 months. Operative resection was undertaken in
      89.4% of cases and multiple surgeries (range 2-5) in 42.2%. Negative resection
      margins were obtained in 72.7% of patients. Univariate analysis comparing
      retroperitoneal versus truncal location demonstrated no significant differences
      in survival. Survival was improved in lower grade tumors (P < 0.02). Liposarcoma
      and fibrosarcoma were associated with improved survival (P < 0.0001).
      Multivariate analysis of pre-treatment variables showed increasing age, grade,
      histopathology (leiomyosarcoma and MFH) and metastasis to be associated with
      worse outcomes. Multivariate analysis of the treatment variables showed that
      surgery and negative resection margins were associated with improved survival (P
      < 0.001). No advantage for chemoradiotherapy could be demonstrated. CONCLUSIONS:
      Successful operative resection can confer prolonged disease-free survival and
      cure for truncal and retroperitoneal sarcomas. Histological subtype, not
      location, is predictive of long-term survival. Future studies should focus on
      histological subtype rather than tumor location for truncal and retroperitoneal
      sarcomas.

PMID- 17206484
TI  - Lymph node involvement in locally advanced cervical cancer patients administered
      preoperative chemoradiation versus chemotherapy.
AB  - BACKGROUND: A retrospective study was planned in 127 locally advanced cervical
      cancer (LACC) to investigate: (1) the rate and pattern of metastatic lymph node
      involvement in patients administered preoperative chemoradiation (CT/RT) versus
      neoadjuvant chemotherapy (NACT), and (2) the profile of clinico-pathological
      parameters predictive of metastatic lymph node involvement in these two clinical
      settings. Finally, we investigated whether the pathologically assessed status of
      lower pelvic nodes (LPN) was able to predict the pathologically assessed status
      of upper pelvic nodes (UPN) and parametrium in cases administered CT/RT. METHODS:
      Patients were selected including LACC patients who were administered concomitant
      CT/RT (n = 87) or NACT (n = 40), before radical surgery. RESULTS: Metastatic
      pelvic lymph node involvement was significantly lower in cases administered CT/RT
      (11.5%) compared to cases administered NACT (30.0%) (P value = 0.009). In the
      CT/RT group, only MRI-assessed pelvic node status (both at staging and post
      treatment evaluation) was associated with pathologic pelvic node status. In
      patients administered CT/RT, the status of LPN appeared associated with the
      status of UPN. CONCLUSIONS: (1) Preoperative CT/RT treatment is associated with a
      lower rate of pelvic node disease in LACC patients compared to NACT; (2) there is
      no association between the preoperative extent of residual cervical disease after
      CT/RT and pathologically assessed pelvic node status; (3) the pathological status
      of LPN is predictive of the pathological status of UPN and parametrium.

PMID- 17206485
TI  - Results of MRI screening for breast cancer in high-risk patients with LCIS and
      atypical hyperplasia.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) can detect breast cancer in high
      risk patients, but is associated with a significant false-positive rate resulting
      in unnecessary breast biopsies. More data are needed to define the role of MRI
      screening for specific high-risk groups. We describe our experience with MRI
      screening in patients with atypical hyperplasia (AH) and lobular carcinoma in
      situ (LCIS). METHODS: We retrospectively reviewed data from our high-risk
      screening program prospective database for the period from April 1999 (when
      screening MRI was first performed at our institution) to July 2005. Patients with
      AH or LCIS demonstrated on previous surgical biopsy were identified. All patients
      underwent yearly mammography and twice yearly clinical breast examination.
      Additional screening MRI was performed at the discretion of the physician and
      patient. RESULTS: We identified 378 patients; 126 had AH and 252 had LCIS. Of
      these, 182 (48%) underwent one or more screening MRIs (mean, 2.6 MRIs; range, 1
      8) during this period, whereas 196 (52%) did not. Those who had MRIs were younger
      (P < 0.001) with stronger family histories of breast cancer (P = 0.02). In MRI
      screened patients, 55 biopsies were recommended in 46/182 (25%) patients, with
      46/55 (84%) biopsies based on MRI findings alone. Cancer was detected in 6/46
      (13%) MRI-generated biopsies. None of the six cancers detected on MRI were seen
      on recent mammogram. All six cancers were detected in five patients (one with
      bilateral breast cancer) with LCIS; none were detected by MRI in the AH group.
      Thus, cancer was detected in 5/135 (4%) of patients with LCIS undergoing MRI. The
      yield of MRI screening overall was cancer detection in 6/46 (13%) biopsies, 5/182
      (3%) MRI-screened patients and 5/478 (1%) total MRIs done. In two additional MRI
      screened patients, cancer was detected by a palpable mass in one, and on
      prophylactic surgery in the other and missed by all recent imaging studies. For
      196 non-MRI-screened patients, 21 (11%) underwent 22 biopsies during the same
      period. Eight of 22 (36%) biopsies yielded cancer in seven patients. All MRI
      detected cancers were stage 0-I, whereas all non-MRI cancers were stage I-II.
      CONCLUSION: Patients with AH and LCIS selected to undergo MRI screening were
      younger with stronger family histories of breast cancer. MRI screening generated
      more biopsies for a large proportion of patients, and facilitated detection of
      cancer in only a small highly selected group of patients with LCIS.

PMID- 17206486
TI  - Papillary lesions: a review of the literature.

PMID- 17206487
TI  - Laparoscopic distal pancreatectomy in children: case report and review of the
      literature.
AB  - BACKGROUND: Laparoscopic resection of benign tumors of the pancreas has been
      reported in adults, but only four cases of partial laparoscopic pancreatectomy in
      children have been described in the English-language literature. METHODS: We
      describe the case of an 11-year-old girl with a solid pseudopapillary tumor who
      was treated with a laparoscopic, spleen-preserving, distal pancreatectomy. The
      specimen was extracted in an endoscopic bag retrieval system through a
      Pfannenstiel incision. Operative time was 120 minutes, and minimal blood loss
      occurred. The literature is reviewed. RESULTS: The postoperative course was
      uneventful. Twenty-two months after the operation, clinical follow-up (including
      assessment of exocrine and endocrine pancreatic function) revealed nothing
      abnormal. The functional and aesthetic results were satisfactory. CONCLUSIONS:
      The technique used for our case is simple and reproducible, was completed safely
      within a reasonable operative time, and yielded a good result.

PMID- 17206488
TI  - Mechanical properties and compositions of tissue engineered and native arteries.
AB  - With the goal of mimicking the mechanical properties of a given native tissue,
      tissue engineers seek to culture replacement tissues with compositions similar to
      those of native tissues. In this report, differences between the mechanical
      properties of engineered arteries and native arteries were correlated with
      differences in tissue composition. Engineered arteries failed to match the
      strengths or compliances of native tissues. Lower strengths of engineered
      arteries resulted partially from inferior organization of collagen, but not from
      differences in collagen density. Furthermore, ultimate strengths of engineered
      vessels were significantly reduced by the presence of residual polyglycolic acid
      polymer fragments, which caused stress concentrations in the vessel wall. Lower
      compliances of engineered vessels resulted from minimal smooth muscle cell
      contractility and a lack of organized extracellular elastin. Organization of
      elastin and collagen in engineered arteries may have been partially hindered by
      high concentrations of sulfated glycosaminoglycans. Tissue engineers should
      continue to regulate cell phenotype and promote synthesis of proteins that are
      known to dominate the mechanical properties of the associated native tissue.
      However, we should also be aware of the potential negative impacts of polymer
      fragments and glycosaminoglycans on the mechanical properties of engineered
      tissues.

PMID- 17206489
TI  - Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in
      inducible nitric oxide synthase deficient mice.
AB  - The ability to genetically manipulate mice has led to rapid progress in our
      understanding of the roles of different gene products in human disease.
      Transgenic mice have often been created in the FVB/NJ (FVB) strain due to its
      high fecundity, while gene-targeted mice have been developed in the 129/SvJ
      C57Bl/6J strains due to the capacity of 129/SvJ embryonic stem cells to
      facilitate germline transmission. Gene-targeted mice are commonly backcrossed
      into the C57Bl/6J (B6) background for comparison with existing data. Genetic
      modifiers have been shown to modulate mammary tumor latency in mouse models of
      breast cancer and it is commonly known that the FVB strain is susceptible to
      mammary tumors while the B6 strain is more resistant. Since gene-targeted mice in
      the B6 background are frequently bred into the polyomavirus middle T (PyMT) mouse
      model of breast cancer in the FVB strain, we have sought to understand the impact
      of the different genetic backgrounds on the resulting phenotype. We bred mice
      deficient in the inducible nitric oxide synthase (iNOS) until they were congenic
      in the PyMT model in the FVB and B6 strains. Our results reveal that the large
      difference in mean tumor latencies in the two backgrounds of 53 and 92 days
      respectively affect the ability to discern smaller differences in latency due to
      the Nos2 genetic mutation. Furthermore, the longer latency in the B6 strain
      enables a more detailed analysis of tumor formation indicating that individual
      tumor development is not stoichastic, but is initiated in the #1 glands and
      proceeds in early and late phases. NO production affects tumors that develop
      early suggesting an association of iNOS-induced NO with a more aggressive tumor
      phenotype, consistent with human clinical data positively correlating iNOS
      expression with breast cancer progression. An examination of lung metastases,
      which are significantly reduced in PyMT/iNOS-/- mice compared with PyMT/iNOS+/+
      mice only in the B6 background, is concordant with these findings. Our data
      suggest that PyMT in the B6 background provides a useful model for the study of
      inflammation-induced breast cancer.

PMID- 17206490
TI  - Effects of paclitaxel and doxorubicin in histocultures of hepatocelular
      carcinomas.
AB  - Cancer has been the leading cause of death in Taiwan over the past two decades
      and liver cancer is the leading cause of all cancer deaths in Taiwan with a trend
      of increase in incidence. Therapeutic options and efficacy for liver cancer have
      been limited and the 5-year survival rate is less than 7% in the Unite States.
      The study was conducted to establish a histoculture system of human
      hepatocellular carcinomas (HCC) for biological and pharmacological studies and to
      determine the efficacy of anticancer drugs with the established HCC
      histocultures. Patient HCC tissues freshly obtained after surgeries were prepared
      and histocultured. The histocultured HCC were treated with doxorubicin and
      paclitaxel of various concentrations for 96-h. Upon drug treatments, the activity
      of tumor cell proliferation and extent of cell death induction were measured and
      changes of the alpha-fetoprotein levels in the culture medium were determined. We
      demonstrated that human HCC can be successfully cultured in a 3-dimensional
      histoculture system and used for pharmacological studies. Doxorubicin and
      paclitaxel showed concentration-dependent activities in anti-proliferation and
      cell death induction against the human HCC. Inhibitory effects of both drugs on
      alpha-fetoprotein production of the cultured HCC were in agreement with their
      anti-proliferative effects. Exposure time-dependent antitumoral effects of
      paclitaxel treatments at 3-, 24-, and 96-h against the histocultured HCC
      PLC/PRF/5 xenograft tumors were also observed. In conclusion, we have
      demonstrated a histoculture system for patient HCC and it can be utilized in
      selection of active drugs prior to treatments in patients and in evaluation of
      new agents against HCC, for which therapeutic agents are in desperate needs
      worldwide.

PMID- 17206491
TI  - Immunohistochemical analysis of collagen types I, III, IV and alpha-actin in the
      urethra of sexually intact and ovariectomized beagles.
AB  - Urinary incontinence is a widespread problem in both postmenopausal women and
      ovariectomized dogs. The objective of this study was to investigate the influence
      of ovariectomy on the immunoreactivity and the distribution pattern of collagens
      I, III, IV and alpha-actin in the canine urethra. The immunohistochemical results
      were evaluated in five sexually intact and five ovariectomized beagles. The
      immunostaining of both collagens I and III delineated urethral connective tissue
      fibres and co-localized within in the fibres of both groups. The basement
      membranes of smooth muscle cells and sinusoids showed marked type IV collagen
      expression, whereas only faint immunoreactivity was present at the urothelial
      stromal interface. No differences could be detected in the expression or
      distribution of the assessed collagen types and actin between ovariectomized and
      control animals. In conclusion, ovariectomy does not appear to have an effect on
      urethral collagens I, III, IV and smooth muscle actin in the dog, as ascertained
      by immunohistochemistry.

PMID- 17206492
TI  - The vertebral fracture cascade in osteoporosis: a review of aetiopathogenesis.
AB  - Once an initial vertebral fracture is sustained, the risk of subsequent vertebral
      fracture increases significantly. This phenomenon has been termed the "vertebral
      fracture cascade". Mechanisms underlying this fracture cascade are inadequately
      understood, creating uncertainty in the clinical environment regarding prevention
      of further fractures. The cascade cannot be explained by low bone mass alone,
      suggesting that factors independent of this parameter contribute to its
      aetiopathogenesis. This review explores physiologic properties that may help to
      explain the vertebral fracture cascade. Differences in bone properties, including
      bone mineral density and bone quality, between individuals with and those without
      osteoporotic vertebral fractures are discussed. Evidence suggests that non-bone
      parameters differ between individuals with and those without osteoporotic
      vertebral fractures. Spinal properties, including vertebral macroarchitecture,
      intervertebral disc integrity, spinal curvature and spinal loading are compared
      in these groups of individuals. Cross-sectional studies also indicate that
      neurophysiologic properties, particularly trunk control and balance, are affected
      by the presence of a vertebral fracture. This review provides a synthesis of the
      literature to highlight the multi-factorial aetiopathogenesis of the vertebral
      fracture cascade. With a more comprehensive understanding of the mechanisms
      underlying this clinical problem, more effective preventative strategies may be
      developed to offset the fracture cascade.

PMID- 17206493
TI  - Dopamine D2 receptor-dependent modulation of striatal NO synthase activity.
AB  - RATIONALE: Striatal nitric oxide (NO)-producing interneurons receive synaptic
      contacts from midbrain dopamine (DA) neurons and are regulated by phasic DA
      transmission. Classic antipsychotic drugs elevate neuronal NO synthase (NOS)
      expression in the rat striatum. Given that NO signaling potently modulates the
      membrane excitability of striatal projection neurons, it is plausible that up
      regulation of NOS activity after DA D2 receptor blockade contributes to the
      therapeutic efficacy and/or motor side effects associated with antipsychotic
      drugs. OBJECTIVES: This study assessed the impact of DA D(2) receptor activation
      on striatal NOS activity in vivo. Characterization of the dopaminergic regulation
      of striatal NO signaling will be relevant for understanding the mechanism(s) of
      action of antipsychotic drugs. MATERIALS AND METHODS: Striatal NO efflux, evoked
      via electrical stimulation of the substantia nigra (SN) or systemic
      administration of the DA D(1) receptor agonist SKF 81297, was assessed in
      anesthetized rats using an NO-selective amperometric microsensor. RESULTS: The
      facilitatory effect of SN stimulation on striatal NO efflux was attenuated by
      systemic administration of the DA D(2) receptor agonist quinpirole. Conversely,
      administration of the DA D(2) receptor antagonist eticlopride augmented evoked NO
      efflux. NO efflux induced by systemic administration of SKF 81297 was attenuated
      by quinpirole and restored by co-administration of quinpirole and eticlopride.
      The facilitatory effect of SKF 81297 on NO efflux was also significantly
      attenuated after pretreatment with the non-specific NOS inhibitor methylene blue.
      CONCLUSIONS: Activation of NO synthesis by phasic DA transmission is down
      regulated via a DA D2 receptor-dependent mechanism. DA D(2) receptor activation
      opposes DA D(1) receptor activation of NO synthesis at a site postsynaptic to the
      DA terminal. Further studies examining NO-DA dynamics may have potential to
      reveal novel therapeutic strategies to treat various brain disorders.

PMID- 17206494
TI  - An investigation of the behavioral actions of ethanol across adolescence in mice.
AB  - RATIONALE: The transition from adolescence into adulthood is characterized by
      rapid maturation of brain systems mediating reward and by increasing
      experimentation with drugs of abuse including ethanol (EtOH). Previous studies
      have found marked differences in sensitivity to the behavioral effects of EtOH in
      adolescent rats as compared to adults, but relatively few studies have been
      conducted in mice. OBJECTIVES: The present study examined sensitivity to various
      behavioral effects of EtOH in C57BL/6J mice at various stages of
      adolescence/adulthood (4, 6, 8 weeks old). Ages were compared for locomotor
      stimulant (open field), anxiolytic-like (elevated plus-maze), memory-impairing
      (Pavlovian fear conditioning) and ataxic (accelerating rotarod) effects of EtOH,
      and the sedative/hypnotic (sleep time) effects of EtOH and pentobarbital. EtOH
      self-administration was compared using a two-bottle choice paradigm. Measures of
      EtOH metabolism were also obtained. RESULTS: Early adolescent mice exhibited
      increased sensitivity to locomotor stimulant (1.5 g/kg), anxiolytic-like (1.5
      g/kg) and ataxic (1.5-2.5 g/kg), but not memory impairing (2.0 g/kg), effects of
      EtOH relative to adults. Early adolescent, and to some extent peri-adolescent,
      mice were less sensitive than adults to the sedative/hypnotic effects of EtOH
      (3.5-4.5 g/kg), but not pentobarbital (40-50 mg/kg). Early adolescent mice showed
      lower EtOH preference, but not EtOH consumption, than adults. Blood EtOH
      concentrations were higher at early time points and lower at later time points
      after (3.0 g/kg) EtOH injection in early and peri-adolescents relative to adults.
      CONCLUSIONS: Present data demonstrate that sensitivity to the acute intoxicating
      effects of EtOH changes across mouse adolescent development in a behavior
      dependent manner.

PMID- 17206495
TI  - Association of functional catechol O-methyl transferase (COMT) Val108Met
      polymorphism with smoking severity and age of smoking initiation in Chinese male
      smokers.
AB  - RATIONALE: Catechol-O-methyltransferase (COMT) is an enzyme involved in the
      degradation and inactivation of the neurotransmitter dopamine, which is important
      in mediating drug reward such as nicotine in tobacco smoke. Different COMT
      alleles encode enzyme whose activity varies from three- to fourfold that may
      affect dopamine levels and alter subjective effects of nicotine. Recent evidence
      also suggests that a COMT polymorphism may be especially important in determining
      an individual's predisposition to developing nicotine dependence. SUBJECTS AND
      METHODS: We studied the COMT Val108Met polymorphism in a male population of 203
      current smokers, 66 former smokers, and 102 non-smokers. The age-adjusted odds
      ratios were estimated by multiple logistic regression models. RESULTS: The
      results showed no significant association of the COMT Val108Met with initiation,
      persistent smoking, or smoking cessation. However, current smokers with the Met
      allele had significantly higher Fagerstrom Test for Nicotine Dependence scores
      (7.5 +/- 2.1 vs 6.8 +/- 1.8, p = 0.018) and started smoking significantly earlier
      (18.4 +/- 4.9 vs 20.1 +/- 5.9 years, p = 0.036). CONCLUSIONS: These results
      suggest that the COMT Val108Met polymorphism may not influence smoking status in
      a Chinese male population but may influence the age at which smoking started and
      smoking severity among smokers. However, the findings must be regarded as
      preliminary because of the relatively small sample size and marginal associations
      and should be replicated in a larger cohort.

PMID- 17206496
TI  - The dynamic vacuum orthosis: a functional and economical benefit?
AB  - In a prospective, randomised study, 27 patients with internally fixed ankle
      fractures were treated post-operatively for a period of six weeks by application
      of either a new dynamic vacuum orthosis with permitted mobilisation to 10 degrees
      -0 degrees -10 degrees at the ankle joint or a synthetic cast. Full weight
      bearing was allowed in both groups after two weeks. The cast group was prescribed
      four weeks of physiotherapy following six weeks of immobilisation. After ten
      weeks, the Olerud and Molander score showed a significant difference in favour of
      the orthosis. Early functional outcomes were significantly better for this group
      after six weeks and ten weeks. Patients in the orthosis group who were in formal
      employment returned to work 24 days earlier than those in the control group.
      Treatment of the orthosis patients took up three to four times less working time
      for the medical personnel. A saving of 38 euros on directly ascertainable costs
      could be evaluated. Rehabilitation of ankle fractures with a dynamic vacuum
      orthosis leads to better early functional results and greater patient
      satisfaction. The orthosis fulfils the conditions for early return to work.
      Treatment with an orthosis not only reduces working time for medical personnel
      but economises on expenditure for treatment and rehabilitation.

PMID- 17206497
TI  - A new classification and guide for surgical treatment of spinal tuberculosis.
AB  - So far, there is no widely accepted classification system based on objective
      findings that can serve as a guide in selecting the treatment method for spinal
      tuberculosis. This retrospective study evaluates patients with spinal
      tuberculosis (Pott's disease) treated with different surgical procedures. Our aim
      was to outline a new classification of spinal tuberculosis. A retrospective
      review of 76 cases (55 male and 25 female patients) of spinal tuberculosis was
      conducted. Five of the patients were treated medically, and the others who were
      treated surgically were classified into three types (I, II and III) according to
      the new classification system for spinal tuberculosis. All 76 patients were
      classifiable by this new system. The most common complication observed was local
      kyphosis (maximum 8 degrees) in type-II patients, but none of the patients needed
      correction. No neurological deterioration was observed in any of the cases. This
      new classification system helps in differentiating the various manifestations of
      spinal tuberculosis and appears to correlate with the surgical treatment of
      spinal tuberculosis. We believe that this new classification system can be used
      as a practical guide in the treatment of Pott's disease.

PMID- 17206498
TI  - Intramedullary fixation of tibial shaft fractures: a comparison of the unlocked
      and interlocked nail.
AB  - The study is a prospective evaluation and comparison. Eighty-two patients with
      tibial shaft fractures were treated with intramedullary fixation by either an
      unlocked nail (ULN) or an interlocked nail (ILN). All patients were followed up
      for 12 months with a functional score evaluation. The patients were divided into
      two groups, based on the method of treatment. The ULN group included 42 patients
      with an average age of 43.1 years. The ILN group included 40 patients with an
      average age of 40.0 years. Both groups were similar in the injury mechanism,
      fracture location, open fracture type and associated medical conditions (all P >
      0.05). The operative time was shorter and the wound size smaller in the ULN group
      when compared to the ILN group (P < 0.001). The union rate, healing time and
      malunion rate were not significantly different between the two groups (P > 0.05).
      Although the functional score showed no difference between the groups (P = 0.3),
      the ILN group had a greater ability to return to their work 6 months after
      surgery (P = 0.03). In conclusion, unlocked nailing for tibial shaft fractures is
      a simple and effective method especially in the treatment of middle-third
      fractures. Interlocked nailing gives stable fixation without cast immobilisation,
      which resulted in a greater ability for the patients to return to their previous
      work 6 months after surgery.

PMID- 17206499
TI  - Differential localization of aquaporin-2 and glucose transporter 4 in polarized
      MDCK cells.
AB  - Membrane water channel aquaporin-2 (AQP2) and glucose transporter 4 (GLUT4)
      exhibit a common feature in that they are stored in intracellular storage
      compartments and undergo translocation to the plasma membrane upon hormonal
      stimulation. We compared the intracellular localization and trafficking of AQP2
      and GLUT4 in polarized Madin-Darby canine kidney cells stably transfected with
      human AQP2 (MDCK-hAQP2) by immunofluorescence microscopy. When expressed in MDCK
      hAQP2 cells, GLUT4 and GLUT4-EGFP were predominantly localized in the perinuclear
      region close to and within the Golgi apparatus, similar to endogenous GLUT4 in
      adipocytes and myocytes. In addition, GLUT4 was occasionally seen in EEA1
      positive early endosomes. AQP2, on the other hand, was sequestered in subapical
      Rab11-positive vesicles. In the basal state, the intracellular storage site of
      GLUT4 was distinct from that of AQP2. Forskolin induced translocation of AQP2
      from the subapical storage vesicles to the apical plasma membrane, which did not
      affect GLUT4 localization. When forskolin was washed out, AQP2 was first
      retrieved to early endosomes from the apical plasma membrane, where it was partly
      colocalized with GLUT4. AQP2 was then transferred to Rab11-positive storage
      vesicles. These results show that AQP2 and GLUT4 share a common compartment after
      retrieval from the plasma membrane, but their storage compartments are distinct
      from each other in polarized MDCK-hAQP2 cells.

PMID- 17206500
TI  - Real-time PCR for quantifying Haemonchus contortus eggs and potential limiting
      factors.
AB  - The purpose of this study was to evaluate the practicality of using real-time PCR
      for quantifying feces-derived trichostrongyle eggs. Haemonchus contortus eggs
      were used to evaluate fecal contaminants, time after egg embryonation, and the
      presence of competing and non-competing DNAs as factors that might interfere with
      generating reproducible results during simplex and multiplex quantitative real
      time PCR (QPCR). Real-time PCR results showed linear quantifiable amplification
      with DNA from five to 75 eggs. However, threshold cycle (C (T)) values obtained
      by amplification of DNA from egg numbers between 75 and 1,000 did not differ
      significantly. Inhibitors of QPCR were effectively removed during DNA extraction
      as exemplified by the absence of any improvement in C (T) values with bovine
      serum albumin or phytase treatments. Changes from egg embryonation could only be
      detected during the first 6 h. Noncompetitive DNA did not appear to impact
      amplification; however, in a multiplex reaction a competing trichostrongyle such
      as Cooperia oncophora can hinder amplification of H. contortus DNA, when present
      at tenfold greater amounts. This study demonstrates the usefulness of QPCR for
      amplification and quantification of trichostrongyle eggs, and identifies
      potential limitations, which may be addressed through multiplex assays or the
      addition of a standard: exogenous DNA target.

PMID- 17206501
TI  - Nitric oxide contributes to host resistance against experimental Taenia
      crassiceps cysticercosis.
AB  - The immune mechanisms that underlie resistance and susceptibility to
      cysticercosis are not completely understood. In this paper, using susceptible
      BALB/c mice and resistant STAT6-/-BALB/c mice, we have analyzed the role of
      nitric oxide (NO) in determining the outcome of murine cysticercosis caused by
      the cestode Taenia crassiceps. After T. crassiceps infection, wild-type BALB/c
      mice developed a strong Th2-like response, produced high levels of IgG1, IgE, IL
      5, IL-4, and discrete levels of NO, and remained susceptible to T. crassiceps
      infection. In contrast, similarly infected BALB/c mice treated with N(omega)
      nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) mounted a
      similar immune response but with lower levels of NO and harbored nearly 100% more
      parasites than N(omega)-nitro-D-arginine methyl ester (D-NAME, inactive
      enantiomer)-treated mice. To further analyze the role of NO in murine
      cysticercosis, we treated STAT6-/-male mice (known to be highly resistant to T.
      crassiceps) with L-NAME during 8 weeks of infection. As expected, STAT6-/-mice
      mounted a strong Th1-like response, produced high levels of IgG2a, IFN-gamma, and
      IL-17, whereas their macrophages displayed increased transcripts of tumor
      necrosis factor (TNF)-alpha as well as inducible nitric oxide synthase (iNOS) and
      efficiently controlled T. crassiceps infection. However, STAT6-/-male mice
      receiving L-NAME mounted a similar immune response but with lower iNOS
      transcripts concomitantly with decreased levels of NO in sera and displayed
      significantly higher parasite burdens. These findings suggest that macrophage
      activation and NO production are effector mechanisms that importantly contribute
      in host resistance to T. crassiceps infection. The immune mechanisms that
      underlie resistance and susceptibility to cysticercosis are not completely
      understood. In this paper, using susceptible BALB/c mice and resistant STAT6-/
      BALB/c mice, we have analyzed the role of nitric oxide (NO) in determining the
      outcome of murine cysticercosis caused by the cestode Taenia crassiceps. After T.
      crassiceps infection, wild-type BALB/c mice developed a strong Th2-like response,
      produced high levels of IgG1, IgE, IL-5, IL-4, and discrete levels of NO, and
      remained susceptible to T. crassiceps infection. In contrast, similarly infected
      BALB/c mice treated with N(omega)-nitro-L-arginine methyl ester (L-NAME, an
      inhibitor of NO synthase) mounted a similar immune response but with lower levels
      of NO and harbored nearly 100% more parasites than N(omega)-nitro-d-arginine
      methyl ester (D-NAME, inactive enantiomer)-treated mice. To further analyze the
      role of NO in murine cysticercosis, we treated STAT6-/-male mice (known to be
      highly resistant to T. crassiceps) with L-NAME during 8 weeks of infection. As
      expected, STAT6-/-mice mounted a strong Th1-like response, produced high levels
      of IgG2a, IFN-gamma, and IL-17, whereas their macrophages displayed increased
      transcripts of tumor necrosis factor (TNF)-alpha as well as inducible nitric
      oxide synthase (iNOS) and efficiently controlled T. crassiceps infection.
      However, STAT6-/-male mice receiving L-NAME mounted a similar immune response but
      with lower iNOS transcripts concomitantly with decreased levels of NO in sera and
      displayed significantly higher parasite burdens. These findings suggest that
      macrophage activation and NO production are effector mechanisms that importantly
      contribute in host resistance to T. crassiceps infection.

PMID- 17206502
TI  - CD4(+), CD8(+), immunoglobulin status and ocular lesions among some
      onchocerciasis-infected rural Nigerians.
AB  - CD4(+), CD8(+), immunoglobulin status and ocular lesions of some onchocerciasis
      infected rural Nigerians as manifested by the presence of microfilariae in their
      skin snips and some chronic symptoms of the parasitic infestation were evaluated.
      The highest mean CD4(+) and mean microfilarial (mff) load of 560 +/- 20.46 unit
      cells/microl and 20 mff/mg were recorded among the individuals within the second
      decade of life, while the least mean CD4+ and mff load of 307.20 +/- 11.23 unit
      cell/microl and 6.5 mff/mg occurred among volunteers after 60 years of age. The
      highest mean CD8(+) of 388.00 +/- 23.71 unit cells/microl occurred at the third
      decade of life. The individuals above 60 years had the least mean CD8(+) of
      350.25 +/- 11.90 unit cells/microl. The volunteers had mean CD4(+) of 372.45 +/-
      109.02 unit cells/microl and mean CD8(+) of 359.42 +/- with an overall
      CD4(+):CD8(+) ratio of 1.04. The mean CD4(+) and mean CD8(+) had positive
      correlation with the mean microfilarial load (r = 0.52 and r = 0.40),
      respectively. The mean IgE, IgG, lgA, IgM, and IgD were 2,074.82 +/- 823.09,
      19.36 +/- 2.49, 3.88 +/- 0.26, 3.59 +/- 0.38, and 0.29 +/- 0.19 mg/dl, and these
      immunoglobulins negatively correlated with the mean microfilarial load at r = 
      0.02, r = -0.15, r = -0.82, r = -0.37, and r = 0.26, respectively. Among these
      immunoglobulins evaluated, only mean IgE (2,074.82 +/- 823 ng/ml) was
      statistically different from the control subjects (0 mg/dl) at t = 3.39, P <
      0.05. In all, the prevalence of the visual impairment and lesions were low. Among
      the six visual lesions, namely, cataract, choroidoretinitis, iridocyclitis,
      glaucoma, sclerosing keratitis, and optic atrophy encountered in Egoro-Eguare,
      only optic atrophy and sclerosing keratitis was reported among the children. The
      female adults had the highest prevalence of reduced vision 20(43.5%). Also, the
      prevalence of choroidoretinitis (2.2%) and iridocyclitis (2.2%) were the least
      prevalent ocular lesions reported among these female adults. The depletion of the
      CD4(+) contributed to the low prevalence of visual impairment and lesions in this
      locality. The depleted CD4(+), CD8(+), and the lower values of IgA, IgM, and IgG
      contributed in the maintenance of chronicity of onchocerciasis in Egoro-Eguare,
      Nigeria.

PMID- 17206503
TI  - Evaluation of bovine abortion associated with Neospora caninum by different
      diagnostic techniques in Mashhad, Iran.
AB  - Twelve aborted foetuses (gestational ranged from 4-9 months) and dams from
      dairies cattle farms in (Mashhad) Iran were analysed to investigate the
      participation of Neospora caninum in abortion. Diagnosis of the infection was
      determined by histopathology, serology (indirect fluorescent antibody test
      [IFAT]) and semi-nested polymerase chain reaction (PCR). A total 33% of bovine
      foetuses were considered to be infected by PCR technique. Microscopic lesions
      consistent with N. caninum infection in foetal brains were observed in 25% of the
      samples, whereas 33% were positive using IFAT (with a cut-off titre of 1:20).
      This study confirms the importance of N. caninum as an important cause of
      abortion in Iran.

PMID- 17206504
TI  - The use of Trichuris suis and other helminth therapies to treat Crohn's disease.
AB  - Infections with gastrointestinal (GI) nematodes are prevalent worldwide, despite
      the fact that anti-helminthic medications are regarded as safe, efficient, and
      widely available globally. In this review, we highlight the potential therapeutic
      benefits that may be realized through the clinical use of Trichuris suis and
      other helminths for Crohn's disease (CD). Long-lived helminthic parasites are
      remarkable in their ability to down-regulate host immunity, protecting themselves
      from elimination, and also minimize severe pathological host changes. This review
      summarizes what is known about the underlying mechanisms that may account for the
      observed patterns in humans treated with helminths for CD. The Th2 arm of the
      immune system is emphasized as a component of primary importance in the
      association between the host immune system and GI nematode infections. Although
      GI nematode infections in humans cause significant morbidity and mortality, the
      existence and nature of protective mechanisms these helminths may confer remain
      largely unclear.

PMID- 17206505
TI  - Morphological and molecular identification of two Paragonimus spp., of which
      metacercariae concurrently found in a land crab, Potamiscus tannanti, collected
      in Yenbai Province, Vietnam.
AB  - Paragonimosis is an important food-borne zoonosis especially in Asian countries.
      Among Paragonimus species, Paragonimus westermani followed by P. skrjabini
      complex are the major pathogens for human paragonimosis in Asia. In addition, P.
      heterotremus is an important pathogen in southern China and the Indochina
      Peninsula and is the only proven species to cause human paragonimosis in Vietnam.
      During a recent survey in Yenbai Province in northern Vietnam, we found small and
      large types of Paragonimus metacercariae often concurrently in mountainous crabs,
      Potamiscus tannanti. Adult worms from those small and large metacercariae were
      obtained separately by experimental infection in dogs and cats. Morphological and
      molecular phylogenetic study based on sequences of ITS2 and a part of CO1 genes
      were performed for the identification of small and large metacercariae and their
      adults. The results showed that small metacercariae and their adults are
      completely identical with P. heterotremus in morphology and molecular genetic
      profiles. In contrast, large metacercariae and their adults have some
      morphological similarities with P. skrjabini and P. harinasutai, but are
      unidentifiable from each other by morphology alone. Molecular phylogenetic tree
      analyses on ITS2 and CO1 genes revealed that large metacercariae and their adults
      were grouped in the same clade and different from any known Paragonimus species.
      Although they share the same ancestor with P. skrjabini complex, their genetic
      distance was considerably different from two other known subspecies, P. skrjabini
      skrjabini and P. skrjabini miyazakii. Our results provide a new insight on the
      phylogeny of the genus Paragonimus.

PMID- 17206506
TI  - In vitro activity of perifosine: a novel alkylphospholipid against the
      promastigote stage of Leishmania species.
AB  - Perifosine is a novel alkylphospholipid. Perifosine has displayed significant
      antiproliferative activity in vitro and in vivo in several human tumor model
      systems and has recently entered phase II clinical trials. Other
      alkylphospholipids have been previously used as antileishmanial agents, and
      miltefosine (Impavido) is now established as the first oral drug for the
      treatment of visceral and cutaneous leishmaniasis. Perifosine showed the higher
      activity against all tested strains. This study demonstrates for, the first time,
      an in vitro activity of perifosine against different species of Leishmania in the
      promastigote stage.

PMID- 17206507
TI  - Leishmania (Viannia) lainsoni (Silveira et al. 1987): ultrastructural aspects of
      the parasite and skin lesion in experimentally infected hamster (Mesocricetus
      auratus).
AB  - Leishmania (Viannia) lainsoni was first described in 1987 in the state of Para,
      in the Brazilian Amazon region. The initial characterization of this parasite was
      performed based only in light microscopy techniques. Posterior studies with this
      Leishmania species, which focused on biochemistry and molecular assays, showed
      its divergent position in the Leishmania genus. In this study, we characterize
      the ultrastructure of culture promastigote forms throughout the growth curve. Our
      results demonstrate a time-dependent accumulation of electron-dense deposit in
      the acidocalcisome matrix. We have also analyzed, by transmission electron
      microscopy, the chronic experimental skin lesion induced in hamster. The
      experimental infection assay showed adhesion of the intracellular parasites to
      the parasitophorous vacuole membrane and the occurrence of free vacuoles in the
      lesion site containing amastigote forms (the amastigote forms morphometrical data
      were summarized). Our morphological evidences suggest a possible alternative
      surviving mechanism for L. (Viannia) lainsoni in chronic lesion site.

PMID- 17206508
TI  - Comparative study of the efficacy of formulations containing fluconazole or
      paromomycin for topical treatment of infections by Leishmania (Leishmania) major
      and Leishmania (Leishmania) amazonensis.
AB  - The development of alternative therapeutic approaches for cutaneous leishmaniasis
      (CL) has received considerable attention in recent research, including the
      identification of formulations for topical treatment. In the present study, the
      activity of two formulations was evaluated in BALB/c mice experimentally infected
      with either Leishmania (Leishmania) major or L. (L.) amazonensis, a hydrophilic
      gel containing 10% paromomycin (PAHG) and a cream containing 1% fluconazole
      (FLUC). After development of ulcerated lesions, infected mice were divided into
      three groups of five animals each: (1) PA group: Lesions were covered with 50
      microl of PAHG; (2) FLUC group: Lesions were covered with 50 microl of FLUC, and
      (3) placebo group: treated with gel without paromomycin. During and after
      treatment, the size of lesions was determined weekly using a caliper. The
      efficacy of PAHG was significantly higher than that observed for FLUC for both
      Leishmania species. The PAHG formulation was effective in promoting the healing
      of ulcers in all animals 28 days after the beginning of treatment, whereas none
      of the animals was cured by FLUC. These results suggest that the PAHG formulation
      could be suitable for clinical studies and may represent an alternative
      formulation for the topical treatment of CL.

PMID- 17206509
TI  - Genetic markers to distinguish Moniezia expansa from M. benedeni (Cestoda:
      Anoplocephalidae) and evidence of the existence of cryptic species in Australia.
AB  - Multilocus enzyme electrophoresis (MEE) was used to genetically compare Moniezia
      spp. collected from sheep and cattle in southern Australia. Fifteen enzyme loci
      were established for the genetic characterisation of individual specimens of
      Moniezia, which represents a significant increase in the number of loci that was
      previously available for these cestodes. Another four enzyme loci were also
      identified as providing potential genetic markers. There were no differences in
      staining activity or banding patterns of different body regions of individual
      cestodes. Fixed genetic differences between Moniezia expansa and Moniezia
      benedeni were detected at 10 (77%) loci. Individuals that lacked the diagnostic
      morphological characters (i.e. the arrangement pattern of the interproglottidal
      glands) could be assigned to either morphospecies based on their MEE profiles.
      Genetic differences were also detected among individuals of the two
      morphospecies. One specimen of M. expansa had fixed genetic differences at 33% of
      enzyme loci when compared to all other specimens of M. expansa. Fixed genetic
      differences were also detected between the two groups of M. benedeni at 12 of 13
      (92%) enzyme loci. This magnitude of genetic difference was greater than that
      detected between the two morphospecies. This provides evidence for the existence
      of cryptic species in the genus Moniezia.

PMID- 17206510
TI  - Molecular characterization of Cyclospora-like organism from dairy cattle.
AB  - Cyclospora cayetanensis was identified as the cause of large outbreaks of
      diarrhea in many parts of the world, but its host range and reservoirs remains
      poorly defined. Recently, oocysts resembling the C. cayetanensis were detected in
      dairy cattle fecal specimens from China. The 18S rDNA from two of these
      Cyclospora-like oocyst specimens from dairy cattle was amplified and sequenced.
      Phylogenetic analysis indicated that these cattle-associated Cyclospora-like
      organisms are nearly identical to each other and belong to the group of primate
      derived Cyclospora, which are the closest known relatives of C. cayetanensis;
      while these cyclosporans constitute a coherent clade within the diverse group of
      Eimeria species. Moreover, on the basis of our finding that ruminant- and avian
      associated Eimeria species are different in MnlI sites, a new PCR-restriction
      fragment length polymorphism protocol with primers NesCycF and NesCycR was
      developed to distinguish the Cyclospora species from ruminant-associated Eimeria
      species.

PMID- 17206511
TI  - Iron therapy for renal anemia: how much needed, how much harmful?
AB  - Iron deficiency is the most common cause of hyporesponsiveness to erythropoiesis
      stimulating agents (ESAs) in end-stage renal disease (ESRD) patients. Iron
      deficiency can easily be corrected by intravenous iron administration, which is
      more effective than oral iron supplementation, at least in adult patients with
      chronic kidney disease (CKD). Iron status can be monitored by different
      parameters such as ferritin, transferrin saturation, percentage of hypochromic
      red blood cells, and/or the reticulocyte hemoglobin content, but an increased
      erythropoietic response to iron supplementation is the most widely accepted
      reference standard of iron-deficient erythropoiesis. Parenteral iron therapy is
      not without acute and chronic adverse events. While provocative animal and in
      vitro studies suggest induction of inflammation, oxidative stress, and kidney
      damage by available parenteral iron preparations, several recent clinical studies
      showed the opposite effects as long as intravenous iron was adequately dosed.
      Thus, within the recommended international guidelines, parenteral iron
      administration is safe. Intravenous iron therapy should be withheld during acute
      infection but not during inflammation. The integration of ESA and intravenous
      iron therapy into anemia management allowed attainment of target hemoglobin
      values in the majority of pediatric and adult CKD and ESRD patients.

PMID- 17206512
TI  - Improving NMR sensitivity by use of salt-tolerant cryogenically cooled probes.

PMID- 17206513
TI  - Na+ recirculation and isosmotic transport.
AB  - The Na(+) recirculation theory for solute-coupled fluid absorption is an
      expansion of the local osmosis concept introduced by Curran and analyzed by
      Diamond & Bossert. Based on studies on small intestine the theory assumes that
      the observed recirculation of Na(+) serves regulation of the osmolarity of the
      absorbate. Mathematical modeling reproducing bioelectric and hydrosmotic
      properties of small intestine and proximal tubule, respectively, predicts a
      significant range of observations such as isosmotic transport, hyposmotic
      transport, solvent drag, anomalous solvent drag, the residual hydraulic
      permeability in proximal tubule of AQP1 (-/-) mice, and the inverse relationship
      between hydraulic permeability and the concentration difference needed to reverse
      transepithelial water flow. The model reproduces the volume responses of cells
      and lateral intercellular space (lis) following replacement of luminal NaCl by
      sucrose as well as the linear dependence of volume absorption on luminal NaCl
      concentration. Analysis of solvent drag on Na(+) in tight junctions provides
      explanation for the surprisingly high metabolic efficiency of Na(+) reabsorption.
      The model predicts and explains low metabolic efficiency in diluted external
      baths. Hyperosmolarity of lis is governed by the hydraulic permeability of the
      apical plasma membrane and tight junction with 6-7 mOsm in small intestine and <
      or = 1 mOsm in proximal tubule. Truly isosmotic transport demands a Na(+)
      recirculation of 50-70% in small intestine but might be barely measurable in
      proximal tubule. The model fails to reproduce a certain type of observations: The
      reduced volume absorption at transepithelial osmotic equilibrium in AQP1 knockout
      mice, and the stimulated water absorption by gallbladder in diluted external
      solutions. Thus, it indicates cellular regulation of apical Na(+) uptake, which
      is not included in the mathematical treatment.

PMID- 17206514
TI  - Comparison of the effects exerted by luminal Ca2+ on the sensitivity of the
      cardiac ryanodine receptor to caffeine and cytosolic Ca2+.
AB  - Ca(2+) released from the sarcoplasmic reticulum (SR) via ryanodine receptor type
      2 (RYR2) is the key determinant of cardiac contractility. Although activity of
      RYR2 channels is primary controlled by Ca(2+) entry through the plasma membrane,
      there is growing evidence that Ca(2+) in the lumen of the SR can also be
      effectively involved in the regulation of RYR2 channel function. In the present
      study, we investigated the effect of luminal Ca(2+) on the response of RYR2
      channels reconstituted into a planar lipid membrane to caffeine and Ca(2+) added
      to the cytosolic side of the channel. We performed two sets of experiments when
      the channel was exposed to either luminal Ba(2+) or Ca(2+). The given ion served
      also as a charge carrier. Luminal Ca(2+) effectively shifted the EC(50) for
      caffeine sensitivity to a lower concentration but did not modify the response of
      RYR2 channels to cytosolic Ca(2+). Importantly, luminal Ca(2+) exerted an effect
      on channel gating kinetics. Both the open and closed dwell times were
      considerably prolonged over the whole range (response to caffeine) or the partial
      range (response to cytosolic Ca(2+)) of open probability. Our results provide
      strong evidence that an alteration of the gating kinetics is the result of the
      interaction of luminal Ca(2+) with the luminally located Ca(2+) regulatory sites
      on the RYR2 channel complex.

PMID- 17206515
TI  - Cholesterol in negatively charged lipid bilayers modulates the effect of the
      antimicrobial protein granulysin.
AB  - The release of granulysin, a 9-kDa cationic protein, from lysosomal granules of
      cytotoxic T lymphocytes and natural killer cells plays an important role in host
      defense against microbial pathogens. Granulysin is endocytosed by the infected
      target cell via lipid rafts and kills subsequently intracellular bacteria. The
      mechanism by which granulysin binds to eukaryotic and prokaryotic cells but lyses
      only the latter is not well understood. We have studied the effect of granulysin
      on large unilamellar vesicles (LUVs) and supported bilayers with prokaryotic and
      eukaryotic lipid mixtures or model membranes with various lipid compositions and
      charges. Binding of granulysin to bilayers with negative charges, as typically
      found in bacteria and lipid rafts of eukaryotic cells, was shown by
      immunoblotting. Fluorescence release assays using LUV revealed an increase in
      permeability of prokaryotic, negatively charged and lipid raft-like bilayers
      devoid of cholesterol. Changes in permeability of these bilayers could be
      correlated to defects of various sizes penetrating supported bilayers as shown by
      atomic force microscopy. Based on these results, we conclude that granulysin
      causes defects in negatively charged cholesterol-free membranes, a membrane
      composition typically found in bacteria. In contrast, granulysin is able to bind
      to lipid rafts in eukaryotic cell membranes, where it is taken up by the
      endocytotic pathway, leaving the cell intact.

PMID- 17206516
TI  - Pharmacology and surface electrostatics of the K channel outer pore vestibule.
AB  - In spite of a generally well-conserved outer vestibule and pore structure, there
      is considerable diversity in the pharmacology of K channels. We have investigated
      the role of specific outer vestibule charged residues in the pharmacology of K
      channels using tetraethylammonium (TEA) and a trivalent TEA analog, gallamine.
      Similar to Shaker K channels, gallamine block of Kv3.1 channels was more
      sensitive to solution ionic strength than was TEA block, a result consistent with
      a contribution from an electrostatic potential near the blocking site. In
      contrast, TEA block of another type of K channel (Kv2.1) was insensitive to
      solution ionic strength and these channels were resistant to block by gallamine.
      Neutralizing either of two lysine residues in the outer vestibule of these Kv2.1
      channels conferred ionic strength sensitivity to TEA block. Kv2.1 channels with
      both lysines neutralized were sensitive to block by gallamine, and the ionic
      strength dependence of this block was greater than that for TEA. These results
      demonstrate that Kv3.1 (like Shaker) channels contain negatively charged residues
      in the outer vestibule of the pore that influence quaternary ammonium
      pharmacology. The presence of specific lysine residues in wild-type Kv2.1
      channels produces an outer vestibule with little or no net charge, with important
      consequences for quaternary ammonium block. Neutralizing these key lysines
      results in a negatively charged vestibule with pharmacological properties
      approaching those of other types of K channels.

PMID- 17206517
TI  - Topology of the type IIa Na+/P(i) cotransporter.
AB  - The type IIa Na(+)/P(i) cotransporter (NaPi-IIa) plays a key role in the
      reabsorption of inorganic phosphate (P(i)) in the renal proximal tubule. The rat
      NaPi-IIa isoform is a protein of 637 residues for which different algorithms
      predict 8-12 transmembrane domains (TMDs). Epitope tagging experiments
      demonstrated that both the N and the C termini of NaPi-IIa are located
      intracellularly. Site-directed mutagenesis revealed two N-glycosylation sites in
      a large putative extracellular loop. Results from structure-function studies
      suggested the assembly of two similar opposed regions that possibly constitute
      part of the substrate translocation pathway for one phosphate ion together with
      three sodium ions. Apart from these topological aspects, other structural
      features of NaPi-IIa are not known. In this study, we have addressed the topology
      of NaPi-IIa using in vitro transcription/translation of HK-M0 and HK-M1 fusion
      vectors designed to test membrane insertion properties of cDNA sequences encoding
      putative NaPi-IIa TMDs. Based on the results of in vitro
      transcription/translation analyses, we propose a model of NaPi-IIa comprising 12
      TMDs, with both N and C termini orientated intracellularly and a large
      hydrophilic extracellular loop between the fifth and sixth TMDs. The proposed
      model is in good agreement with the prediction of the NaPi-IIa structure obtained
      by the hidden Markov algorithm HMMTOP.

PMID- 17206518
TI  - Permeability changes of Manduca sexta midgut brush border membranes induced by
      oligomeric structures of different cry toxins.
AB  - The pore-formation activity of monomeric and oligomeric forms of different Cry1
      toxins (from Cry1A to Cry1G) was analyzed by monitoring ionic permeability across
      Manduca sexta brush border membrane vesicles. The membrane vesicles were isolated
      from microvilli structures, showing a high enrichment of apical membrane markers
      and low intrinsic K(+) permeability. A fluorometric assay performed with 3,3'
      dipropylthiodicarbocyanine fluorescent probe, sensitive to changes in membrane
      potential, was used. Previously, it was suggested that fluorescence
      determinations with this dye could be strongly influenced by the pH, osmolarity
      and ionic strength of the medium. Therefore, we evaluated these parameters in
      control experiments using the K(+)-selective ionophore valinomycin. We show here
      that under specific ionic conditions changes in fluorescence can be correlated
      with ionic permeability without effects on osmolarity or ionic strength of the
      medium. It is extremely important to attenuate the background response due to
      surface membrane potential and the participation of the endogenous permeability
      of the membrane vesicles. Under these conditions, we analyzed the pore-formation
      activity induced by monomeric and oligomeric structures of different Cry1 toxins.
      The Cry1 toxin samples containing oligomeric structures correlated with high pore
      activity, in contrast to monomeric samples that showed marginal pore-formation
      activity, supporting the hypothesis that oligomer formation is a necessary step
      in the mechanism of action of Cry toxins.

PMID- 17206519
TI  - Factors associated with religious congregation members' support to people living
      with HIV/AIDS in Kumasi, Ghana.
AB  - Physical, social and economic constraints often limit the ability of people
      living with HIV/AIDS to meet their basic needs. Community members are a valuable
      source of support for people living with HIV/AIDS, although little is known about
      the types of support they provide or how to mobilize this support. To examine
      this issue, a survey of 1200 members of 6 religious congregations was conducted
      in Kumasi, Ghana. A fifth of congregation members reported providing some support
      to people with HIV/AIDS in the last 6 months, mostly through prayer, financial
      support, and counseling. Factors associated with providing support include having
      heard a congregation or tribal chief speaking about HIV/AIDS, collective efficacy
      related to HIV/AIDS, and perceived risk of becoming infected with HIV. To enhance
      support to people with HIV/AIDS, programs should involve community leaders and
      encourage dialogue on ways to address the epidemic.

PMID- 17206520
TI  - A comparative analysis of functional cerebral asymmetry in lesbian women,
      heterosexual women, and heterosexual men.
AB  - This study tested dichotic listening performance, a measure of functional
      cerebral asymmetry previously shown to be sexually dimorphic, in homosexual women
      (n=23), heterosexual women (n=27), and heterosexual men (n=24). All participants
      completed a verbal consonant-vowel dichotic listening task. On three laterality
      indices, heterosexual men displayed a significantly greater right-ear advantage
      compared to heterosexual women only. Homosexual women did not differ
      significantly from heterosexual men or from heterosexual women. Post-hoc
      comparisons (with a statistical correction) for each ear separately showed that
      heterosexual men displayed significantly greater right-ear scores compared to
      heterosexual women only. These data suggest that lesbian women are somewhat
      masculinized in their functional cerebral asymmetry. The results were interpreted
      in the context of sexual variation in models of linguistic hemispheric
      processing.

PMID- 17206521
TI  - Recent developments in the use of animal models of psychiatric disease-
      introduction to special issue.

PMID- 17206522
TI  - Predictors of optimal outcome in toddlers diagnosed with autism spectrum
      disorders.
AB  - A diagnosis of autism spectrum disorder (ASD) is usually taken to be permanent.
      In this study, 13 two-year-old children with ASD lost the diagnosis by age 4, at
      which time they scored within the normal range on standardized measures of
      cognitive and adaptive functioning. No differences were found in symptom
      severity, socialization, or communication between children who lost the ASD
      diagnosis and children who did not, but children with PDD-NOS were significantly
      more likely than those with full autistic disorder to move off the spectrum. The
      clearest distinguishing factor was motor skills at age 2. Results support the
      idea that some toddlers with ASD can lose their diagnosis and suggest that this
      is difficult to predict.

PMID- 17206523
TI  - Atomic force and confocal microscopy for the study of cortical cells cultured on
      silicon wafers.
AB  - The primary cortical cells were selected as a model to study the adherence and
      neural network development on chemically roughened silicon substrates without any
      coatings using confocal laser scanning microscopy (CLSM) and atomic force
      microscopy (AFM). The silicon substrates have a nano-range roughness (RMS)
      achieved by chemical etching using hydrofluoric (HF) acid. After 7 days of
      culturing, the neurons were observed to connect together and form dense neural
      networks. Furthermore, AFM results revealed that some porous structures at a few
      micrometer range existed between the neuron cells and the silicon substrates. It
      is suggested that the porous structures are made of extracellular matrix (ECM)
      components and play an important role in the neuronal adhesion and neurite
      outgrowth on the inert silicon wafers.

PMID- 17206524
TI  - Population pharmacokinetics of nicotine and its metabolites I. Model development.
AB  - We present a mechanistic population model for the pharmacokinetics of nicotine
      (NIC), its primary (CYP2A6-generated) metabolite cotinine (COT), and COT's
      primary (CYP2A6-generated) metabolite, trans-3'-hydroxycotinine (3HC). Sixty-six
      subjects received oral deuterium-labeled NIC (NIC-d(2), 2 mg), and COT (COT-d(4),
      10 mg) simultaneously. Frequent plasma/saliva samples were taken for measurement
      of concentrations of NIC-d(2), COT-d(2), 3HC-d(2), COT-d(4), and 3HC-d(4). A
      mechanistic population pharmacokinetic model was fitted to all data
      simultaneously. Most of the pharmacokinetic parameters found here agree with
      previous studies and with a previous model-independent analysis of these data.
      However, 3HC t(1/2) was found to be considerably shorter than a previously
      reported value, possibly because 3HC elimination was saturated with the larger
      doses used in the previous study. Additionally, the delay in the appearance of
      COT-d(2) in the blood was modeled as a time delay (t(1/2) = 12 min) in its
      release from the liver following NIC-d(2) administration. The most important
      result of the previous model-independent analysis of these data, confirmed here,
      is that NIC clearance to COT and the 3HC:COT saliva concentration ratio are
      highly correlated (r = 0.7-0.8). The correlation above support that idea that the
      3HC:COT ratio can be used as a predictor of CYP2A6 activity and nicotine
      clearance. The model-based analysis extends and further justifies this
      conclusion.

PMID- 17206525
TI  - Prediction methods for nicotine clearance using cotinine and 3-hydroxy-cotinine
      spot saliva samples II. Model application.
AB  - To develop and compare methods that predict individual nicotine (NIC) clearance,
      which reflects CYP2A6 activity, using random saliva cotinine (COT) and trans 3'
      hydroxycotinine (3HC) measurements. COT and 3HC saliva concentrations in smokers
      were simulated utilizing a mechanistic population pharmacokinetic model of NIC
      metabolism that was adapted from the one described in a companion paper. Four
      methods to predict NIC clearance using the metabolites concentrations were
      compared. The precision bias, and the fraction of predictions that are made with
      an absolute error below 25% were the performance measures evaluated. Four
      prediction methods were compared: (M1) reference method, an intercept slope model
      of the metabolite concentration ratios ([3HC]/[COT]) (M2) an intercept slope
      model of the natural logarithm of the metabolite ratios (M3) a spline of the
      logarithm of the metabolite ratios (M4) Maximal Posteriori Bayesian estimate of
      NIC clearance conditioned on the model, COT and 3HC concentrations. In addition,
      the effect of smoking patterns on the concentrations of COT and 3HC was
      evaluated. The precision, accuracy, and the fraction of predictions with an
      absolute error below 25%, were higher for methods M2-M4 compared to method M1.
      However, the differences between M2 and M4 were small. Additionally, smoking
      pattern did not affect the metabolite concentration profiles. Predicting NIC
      clearance using an intercept slope model of the natural logarithm of the ratio of
      3HC to COT appears to be a relatively simple method that is better than using the
      metabolite ratio directly. This method has a bias of approximately -10%,
      precision of approximately 60%. The fraction of estimates below an absolute error
      of 25% is 43%. These results support use of M2 to estimate CYP2A6 activity in
      smokers in the clinical setting.

PMID- 17206526
TI  - GPR54 and KiSS-1: role in the regulation of puberty and reproduction.
AB  - The finding of inactivating mutations in GPR54 in IHH patients and the lack of
      reproductive maturation of the GPR54 null mouse have uncovered a previously
      unrecognized role for GPR54 and KiSS-1 in the physiologic regulation of puberty
      and reproduction. This newly identified function for GPR54 and its cognate
      ligand, kisspeptin, has led to additional studies that have localized GPR54 and
      KiSS-1 mRNA in the hypothalamus, colocalized GPR54 in GnRH neurons, demonstrated
      GnRH-dependent activation of LH and FSH release by kisspeptin, and shown
      increased hypothalamic KiSS-1 and GPR54 mRNA levels at the time of puberty. Taken
      together, these findings establish the role of the kisspeptin-GPR54 system in the
      stimulation of GnRH neurons during puberty. The mechanisms by which kisspeptin
      activates GnRH release, as well as the trigger for this pathway at the onset of
      puberty, are yet to be elucidated. In the future, modulators of GPR54 activity,
      including kisspeptin, may prove valuable in clinical applications in the fields
      of both cancer therapy and reproductive medicine.

PMID- 17206527
TI  - The "literally" (and not so literally) homeless.

PMID- 17206528
TI  - More flowerpots, less smoking?

PMID- 17206529
TI  - Physical activity and risk of colorectal cancer in Japanese men and women: the
      Japan Public Health Center-based prospective study.
AB  - OBJECTIVE: To prospectively examine the association between physical activity and
      the risk of developing colorectal cancer in a large population-based cohort study
      of Japanese men and women, and to investigate whether the effects of physical
      activity on colorectal cancer risk differ by sex and subsite. METHODS: We
      analyzed data from a population-based cohort of 65,022 subjects. A total of 486
      incident colorectal cancers (154 proximal colon, 166 distal colon and 149 rectal
      cancers) was identified during 6 years of follow-up. RESULTS: We observed a
      significant inverse association between physical activity and the risk of
      developing colorectal cancer, particularly colon cancer, among men. Relative to
      men in the lowest level of metabolic equivalent (MET) hours per day, those in the
      highest level had a RR of 0.69 (95% CI = 0.49-0.97). A significant decrease in
      risk of colorectal cancer was associated with increasing MET hours per day among
      men. This inverse association was essentially limited to colon cancer. A
      significant decrease in risk with increasing MET-hour score was observed
      predominantly for proximal colon cancer among men. In contrast, no significant
      decrease was seen among women. CONCLUSION: These findings suggest that physical
      activity may prevent colon cancer among Japanese men.

PMID- 17206530
TI  - Association of MTHFR C677T and SHMT(1) C1420T with susceptibility to ESCC and GCA
      in a high incident region of Northern China.
AB  - OBJECTIVE: To assess the association between the C to T transition in the
      methylenetetrahydro folate reductase gene (MTHFR C677T) and the C to T transition
      in the serine hydroxymethyltransferase ( 1 )gene (SHMT ( 1 ) C1420T) and the
      increased risk of carcinogenesis of esophageal squamous cell carcinoma (ESCC) and
      gastric cardia adenocarcinoma (GCA) in a population of high incident region of
      Northern China. METHODS: The polymorphisms were genotyped by polymerase chain
      reaction-restriction fragment length polymorphism and PCR-confronting two-pair
      primers analysis respectively among 1051 cancer patients (584 ESCC and 467 GCA)
      and 540 healthy controls. RESULTS: The MTHFR 677T/T genotype significantly
      increased susceptibility to both ESCC and GCA compared with the C/C genotype, the
      adjusted OR was 2.13 (95% CI = 1.50-3.02) and 1.28 (95% CI = 1.07-1.53,
      respectively. For the SHMT ( 1 ) C1420T polymorphism, the C/C genotype was
      significantly associated with the increased risk of ESCC and GCA, compared with
      the C/T genotype (the adjusted OR = 1.43 and 1.35, 95% CI = 1.02-2.00 and 1.11
      1.63, respectively). The interactive influence of the MTHFR and SHMT ( 1 )
      polymorphisms in the risk of ESCC and GCA was also observed. CONCLUSION: The
      association between the MTHFR C677T and SHMT ( 1 ) C1420T polymorphisms and the
      risk of ESCC and GCA was demonstrated.

PMID- 17206531
TI  - Examination of gender effect in birth weight and miscarriage associations with
      childhood cancer (United Kingdom).
AB  - BACKGROUND: Higher birth weight and maternal history of miscarriage has been
      associated with an increased risk of childhood leukemia. The possibility that
      this association may be sex-specific has not been explored in detail in previous
      studies. METHODS: In a retrospective case-control study, 732 childhood (< or =14
      years) cancer cases from a population-based Registry in Northern England whose
      hospital birth records could be accessed and 3,723 controls matched for date and
      hospital of birth to the cases were compared. We examined birth weight for sex
      specific associations with childhood cancer. Conditional logistic regression
      analysis was used for statistical evaluation of associations. RESULTS: In acute
      lymphoblastic leukemia (ALL) (225 cases and 1,163 matched controls), birth weight
      and sex showed a strong interaction (P = 0.003). In boys with ALL, but not in
      girls, there was a nonlinear association with birth weight (P for trend = 0.008;
      OR = 3.05 for the highest quintile compared to the second lowest quintile, 95% CI
      = 1.40-6.64; P = 0.005). When birth weights were adjusted using UK standards for
      gestational age and sex, the risk associations were similar in statistical
      significance and magnitude. Maternal history of miscarriage showed an association
      with all cancers and individually with ALL. The miscarriage association with ALL
      was statistically significant in boys only (OR = 1.91, 95% CI = 1.07-3.42; P =
      0.03). A multivariable model for ALL containing other examined maternal and
      reproductive variables confirmed the independence of the birth weight and
      miscarriage associations. There was no birth weight or miscarriage associations
      in other cancers. CONCLUSIONS: This study confirmed the risk associations with
      birth weight and miscarriages in childhood ALL. Statistically significant
      association of size at birth suggested marked differences in etiology between
      girls and boys.

PMID- 17206532
TI  - Ambient UV, personal sun exposure and risk of multiple primary melanomas.
AB  - OBJECTIVE: Sun exposure is the main cause of melanoma in populations of European
      origin. No previous study has examined the effect of sun exposure on risk of
      multiple primary melanomas compared with people who have one melanoma. METHODS:
      We identified and enrolled 2,023 people with a first primary melanoma (controls)
      and 1,125 with multiple primary melanomas (cases) in seven centers in four
      countries, recorded their residential history to assign ambient UV and
      interviewed them about their sun exposure. RESULTS: Risk of multiple primary
      melanomas increased significantly (P<0.05) to OR=2.10 for the highest exposure
      quarter of ambient UV irradiance at birth and 10 years of age, to OR=1.38 for
      lifetime recreational sun exposure, to OR=1.85 for beach and waterside
      activities, to OR=1.57 for vacations in a sunnier climate, to OR=1.50 for
      sunburns. Occupational sun exposure did not increase risk (OR=1.03 for highest
      exposure). Recreational exposure at any age increased risk and appeared to add to
      risk from ambient UV in early life. CONCLUSIONS: People who have had a melanoma
      can expect to reduce their risk of a further melanoma by reducing recreational
      sun exposure whatever their age. The same is probably true for a person who has
      never had a melanoma.

PMID- 17206533
TI  - Family history of hematopoietic and non-hematopoietic malignancies and risk of
      non-Hodgkin lymphoma.
AB  - BACKGROUND: Family history of hematopoietic malignancies has been linked to the
      risk of non-Hodgkin lymphoma (NHL). The relationship between family history of
      specific hematopoietic and non-hematopoietic malignancies and the risk of NHL and
      by NHL subtypes are unclear. METHODS: We analyzed data from a population-based
      case-control study in Connecticut women. A total of 601 histologically confirmed
      NHL incident cases and 717 randomly selected controls were included in the study.
      Unconditional logistic regression was used to estimate the association between
      family cancer history and risk of NHL overall and by NHL subtypes. RESULTS:
      Compared to women who reported to have no family history of any malignancies in
      first-degree relatives, those who reported to have a family history of lymphoma
      (OR = 2.2, 95%CI: 1.1-4.5) or leukemia (OR = 2.5, 95%CI: 1.2-5.2) had an
      increased risk of NHL. The risk was higher among women who had a sibling with
      lymphoma or leukemia than those who had parents with lymphoma or leukemia.
      Several non-hematopoietic malignancies in first-degree relatives, including
      cancer of the lung (OR = 1.7, 95%CI: 1.1-2.6) in first-degree relatives, stomach
      (OR = 2.2, 95%CI: 0.8-5.9) and pancreas (OR = 2.6, 95%CI: 0.9-7.1) in parents, as
      well as liver (OR = 5.0, 95%CI: 1.0-24.6), breast (OR = 2.2, 95%CI: 1.3-3.9),
      cervix (OR = 7.5, 95%CI: 0.9-64.9), and ovary (OR = 3.5, 95%CI: 1.1-11.5) in
      siblings were also associated with an increased risk of NHL. CONCLUSIONS: The
      risk associated with a family history of malignancies in first degree-relatives
      appears to vary by type of first-degree relatives.

PMID- 17206534
TI  - Screening for prostate cancer: a Cochrane systematic review.
AB  - OBJECTIVES: The objective of this systematic review was to determine whether
      screening for prostate cancer reduces prostate cancer mortality. METHODS: A
      systematic search for randomised controlled trials was conducted through
      electronic scientific databases and a specialist register of the Cochrane
      Prostatic Diseases and Urologic Cancers Group. Manual searching of specific
      journals was also conducted. Two authors independently reviewed studies that met
      the inclusion criteria. Studies were independently assessed for quality. Data
      from included studies was also extracted independently. RESULTS: Two randomised
      controlled trials were included however, both trials had methodological
      weaknesses. Re-analysis of the reported data using intention-to-screen and meta
      analysis indicated no statistically significant difference in prostate cancer
      mortality between men randomized for prostate cancer screening and controls (RR
      1.01, 95% CI: 0.80-1.29). CONCLUSIONS: Given that only two randomised controlled
      trials were included, and the high risk of bias of both trials, there is
      insufficient evidence to either support or refute the routine use of screening
      compared to no screening for reducing prostate cancer mortality. Currently, no
      robust evidence from randomised controlled trials is available regarding the
      impact of screening on quality of life, harms of screening, or its economic
      value. Results from two ongoing large scale multi-center randomised controlled
      trials, which will be available in the upcoming few years, will assist patients
      and health professionals in making an evidence-based decision regarding the
      effectiveness of screening for prostate cancer.

PMID- 17206535
TI  - Physical activity and endometrial cancer risk: a review of the current evidence,
      biologic mechanisms and the quality of physical activity assessment methods.
AB  - OBJECTIVES: To (1) determine the nature of the association between physical
      activity and endometrial cancer risk; (2) assess the contribution of variation in
      the quality of physical activity measurement to inconsistencies in study results;
      and (3) review the biologic mechanisms that might mediate possible effects of
      physical activity on risk. METHODS: We reviewed and summarized all published
      epidemiologic studies examining physical activity and endometrial cancer risk,
      and evidence relating to possible biologic mechanisms. We assigned each study a
      quality score for physical activity measurement. RESULTS: Fourteen of the 18
      studies showed a convincing or possible protective effect of physical activity on
      endometrial cancer risk, with an average relative risk reduction of around 30%. A
      dose-response relation was observed in 7 of 13 studies. The quality score was not
      related to the observed strength of association or the presence of a dose
      response relation. There was epidemiologic and biologic evidence that vigorous
      activity, as well as light and moderate intensity activities, such as housework,
      gardening or walking for transportation, may reduce risk. CONCLUSIONS: Physical
      activity probably has a protective role in endometrial cancer development. More
      epidemiologic and biologic evidence is needed to make conclusive recommendations
      on optimal types, characteristics or time periods of physical activity.

PMID- 17206536
TI  - Sexual risk behavior and venues for meeting sex partners: an intercept survey of
      gay and bisexual men in LA and NYC.
AB  - Understanding the link between venues for meeting sex partners and sexual risk
      behavior is critical to developing and placing effective sexual health education
      and HIV prevention services. Non-monogamous gay and bisexual men (n = 886) were
      surveyed in New York and Los Angeles about the venues that they met recent sex
      partners: bathhouses, private sex parties, gay bars/clubs, the gym, via public
      cruising, and the Internet. Bars/clubs, bathhouses, and the Internet were the
      most endorsed venues for meeting partners. Men having met a majority of their
      partners (i.e., "preference") via these three venues were compared/contrasted.
      Those having preference for bars/clubs were dissimilar from men with preference
      for bathhouses or the Internet on multiple levels (e.g. age, number of sex
      partners, temptation for unsafe sex). However, these men were proportionally
      similar in whether they had engaged in a recent episode of unprotected anal
      intercourse (UAI). Logistic regressions predicting UAI suggested venues might not
      play a role in differentiating men who had preference for bars/clubs, bathhouses
      or the Internet. Additional regression analyses utilizing all six venues to
      predict UAI suggested other person-factors such as identity as a barebacker and
      temptation for unsafe sex better explain UAI. This research suggests HIV
      prevention and educational campaigns targeted within venues need also address
      socio-psychological person-factors in addition to environmental/venue contexts.

PMID- 17206537
TI  - Radio-frequency ablation of arrhythmias following congenital heart surgery.
AB  - BACKGROUND: Cardiac arrhythmias as a late complication following congenital heart
      surgery are encountered more and more frequently in clinical practice. The use of
      new electrophysiological methods of visualisation and mapping improves the
      efficacy of radio-frequency (RF) ablation of these arrhythmias. AIM: To assess
      patterns of atrial arrhythmias following congenital heart surgery and to examine
      the efficacy of RF ablation using the electro-anatomical CARTO system. METHODS:
      Electrophysiological diagnostic study and RF ablation were performed in 24
      consecutive patients (mean age 36+/-18 years) who had atrial arrhythmias
      following congenital heart surgery. The mechanism of arrhythmia (ectopic or
      reentrant) and strategy of RF ablation procedure were based on the results of the
      right atrial map performed during index arrhythmia. RESULTS: The patients were
      divided into five groups according to the type of congenital heart surgery. The
      ASD group consisted of 17 patients who had undergone in the past surgery due to
      atrial septal defect, four patients had a history of surgery due to ventricular
      septal defect (VSD group), and one patient each had undergone surgery due to
      corrected transposition of the great arteries (ccTGA), tetralogy of Fallot (TF)
      or dual-outflow right ventricle (DORV). During diagnostic electrophysiological
      study typical atrial flutter (AFL) was diagnosed in nine patients from the ASD
      group, atypical AFL in three ASD patients, and ectopic atrial tachycardia (EAT)
      in six ASD patients. In one patient EAT was induced after ablation of typical
      AFL. Of the VSD patients, three had atypical AFL, and one had typical AFL. The
      patient following surgery for ccTGA had atypical AFL and EAT, whereas in the two
      remaining patients (DORV and TF) atypical AFL was demonstrated. The efficacy of
      the first session of RF ablation was 83% and no complications were observed. The
      efficacy of RF ablation of typical AFL was 90%, atypical AFL 78%, and EAT 86%
      (NS). During the long-term follow-up (24+/-17 months) arrhythmia recurrences were
      noted in 2 (10%) out of 20 patients who were effectively treated during the first
      RF ablation session. CONCLUSIONS: Reentry is the most common electrophysiological
      mechanism of incisional tachycardias, followed by ectopic atrial tachycardia. RF
      ablation using the electro-anatomical CARTO system is effective and safe in this
      group of patients.

PMID- 17206538
TI  - The effect of glycoprotein IIIa A1/A2 gene polymorphism on one-year outcome in
      patients with ST-segment elevation myocardial infarction treated with primary
      percutaneous coronary intervention.
AB  - INTRODUCTION: Glycoprotein IIb/IIIa (GP IIb/IIIa) is a platelet receptor composed
      of two subunits coded by individual genes. GP IIIa gene has two alleles: A1 and
      A2. The A2 allele determines higher platelet activity and was investigated many
      times as a potential risk factor of ACS. The influence of A1/A2 polymorphism on
      the prognosis in patients with ST-segment elevation myocardial infarction (STEMI)
      has not been analysed so far. AIM: Evaluation of the relationship between GP
      IIb/IIIa A1/A2 gene polymorphism and one-year prognosis in patients with STEMI
      treated with primary percutaneous coronary intervention (pPCI). METHODS: 171
      patients (23.9%--women, 39.7%--anterior MI) with STEMI treated successfully with
      pPCI as well as 121 healthy subjects from a reference group were enrolled in the
      study. Genotyping was performed using restriction fragment length polymorphism
      analysis (RFLP). In one-year follow-up the primary end point included deaths and
      infarctions. The following methods were used in statistical analysis: chi(2) as
      well as Mann-Whitney test, Kaplan-Meier survival analysis, Cox regression model
      and multivariate analysis. RESULTS: The percentage of A2 allele carriers was
      similar in STEMI patients and in subjects from the reference group (27.4% vs.
      21.5%, p=0.24). No statistically significant difference in the incidence of
      primary end point between the A1A1 homozygotes and A2 allele carriers (A1A2/A2A2
      genotype) was observed among STEMI patients. In Cox regression analysis, the
      variables associated with death or MI were: ejection fraction (RR 0.912, p=0.01)
      and systolic blood pressure on admission (RR 0.97, p=0.049). The variables
      categorised as unfavourable predictors included: Killip class >2 and heart ratio
      on admission >100/min (p <0.05, log-rank test). CONCLUSION: No relationship
      between GP IIb/IIIa A1/A2 gene polymorphism and STEMI incidence as well as one
      year prognosis in patients with STEMI treated with pPCI was documented.

PMID- 17206539
TI  - Effects of high-dose statin administered prior to coronary angioplasty on the
      incidence of cardiac events in patients with acute coronary syndrome.
AB  - INTRODUCTION: Statins given after acute coronary syndrome without ST elevation
      (NSTE-ACS) reduce the incidence of major adverse cardiac events (MACE) in long
      term follow-up. AIM: To evaluate the effects of high-dose statin administered in
      patients with NSTE ACS and increased CRP level prior to percutaneous coronary
      intervention (PCI) on the incidence of MACE in long-term follow-up. METHODS: The
      study involved 140 consecutive patients with NSTE ACS and increased CRP level at
      baseline. Patients from group A (n=54) did not receive statin before PCI, whereas
      subjects in group B (n=86) were given 80 mg of atorvastatin. Patients in both
      groups received typical cardiological therapy including aspirin, thienopyridine
      and low molecular weight heparin. After PCI all patients received 40 mg of
      atorvastatin. Incidence of MACE (death, myocardial infarction (MI), re-PCI)
      during long-term followup was evaluated in both groups. RESULTS: Study groups did
      not differ with respect to demographic parameters and rate of ischaemic heart
      disease risk factors. Also, no differences occurred regarding CRP level (group A
      vs. B: hsCRP 10.8+/-1.8 mg/l vs. 8.2+/-2.8 mg/l; p=NS) and TIMI Risk Score (group
      A vs. B: 4.3+/-0.71 vs. 4.37+/-0.79; p=NS). During long-term follow-up the
      incidence of MI (9.25% vs. 1.2%, p=0.03), composite endpoint: death + MI (14.8%
      vs. 2.32%, p=0.013) and death + MI + re PCI (25.9% vs. 8.1%, p=0.006) was
      significantly higher in group A than group B. CONCLUSIONS: Administration of high
      dose statin in NSTE ACS patients before PCI was associated with significant
      reduction of MACE in long-term follow-up. This effect was observed despite the
      same therapy given after PCI.

PMID- 17206540
TI  - The relationship between serum LDL-cholesterol, HDL-cholesterol and systolic
      blood pressure in patients with type 2 diabetes.
AB  - BACKGROUND: The prevalence of hypertension and lipid disorders is increased in
      patients with diabetes. The relationship between cholesterol and blood pressure
      values has not yet been well established in this group of patients. AIM: To
      assess the correlation between lipid levels and blood pressure values in patients
      with type 2 diabetes. METHODS: The study group consisted of 122 patients (82
      females, 40 males, mean age 63+/-10 years) with type 2 diabetes. The mean
      duration of diabetes was 7.4+/-5.8 years, and hypertension 3.2+/-4.6 years. In
      all patients glycosylated haemoglobin (HbA1c) and lipid serum concentrations were
      assessed. RESULTS: The mean serum LDL-cholesterol was 112+/-37 mg/dl (median: 112
      mg/dl) and HDL-cholesterol - 47+/-18 mg/dl (median: 44 mg/dl). A significant
      inverse correlation between HDL-cholesterol and systolic blood pressure (r=
      0.177, p=0.05) as well as a positive correlation between LDL-cholesterol and
      systolic blood pressure values (r=0.196, p=0.031) were found. CONCLUSION: In
      patients with type 2 diabetes there is a significant relationship between lipid
      levels and blood pressure values, which suggests an increased susceptibility to
      vascular disease associated with LDL-cholesterol in these patients.

PMID- 17206541
TI  - [Percutaneous ablation of the segmental renal artery for the treatment of the
      arterio-pelvic fistula complicating percutaneous nephrolithotomy--a case report].
AB  - We present a case of an 18-year-old female who underwent two percutaneous
      nephrolithotomy procedures complicated with haematuria. Angiography revealed the
      presence of an aneurysm of the right superior renal artery branch and arterio
      pelvic fistula. The aneurysm was successfully obliterated using alcohol injection
      via coronary balloon catheter.

PMID- 17206542
TI  - [Isolated non-compaction of the left ventricular myocardium in a neonate--a case
      report].
AB  - We describe a case of a neonate who developed cardiogenic shock 24 days after
      birth. Echocardiography revealed congenital anomaly--isolated non-compaction of
      the left ventricular myocardium. Medical treatment was effective. The whole
      clinical presentation suggests the Barth syndrome. The diagnosis and treatment of
      this condition are discussed.

PMID- 17206543
TI  - [Cardiac tamponade due to angiosarcoma--was surgical treatment necessary? A case
      report].
AB  - We present a case of a 49-year-old patient with cardiac tamponade due to
      haemopericardium. The decision to perform surgery, although controversial,
      allowed to diagnose cardiac angiosarcoma with metastases to pericardium, vena
      cava superior and pulmonary trunk. Consequently, chemotherapy was instituted and
      was initially effective, however, the patient died 12 months later due to the
      progression of the disease.

PMID- 17206544
TI  - [Aortic dissection type B with aortic arch involvement surgically treated--a case
      report].
AB  - A case of a 56-year-old male with acute aortic dissection type B is presented.
      The patient underwent successful surgery which was very difficult due to the
      extent of aortic dissection.

PMID- 17206545
TI  - [Ezetimibe--intestinal cholesterol absorbtion inhibitor].

PMID- 17206546
TI  - [Electrocardiogram with diffuse ST-segment changes--acute ischaemia or something
      else?].

PMID- 17206547
TI  - [Complication of the right heart angiography in 2-months old baby-
      echocardiography assessment].

PMID- 17206548
TI  - [Efficient revascularization of totally blocked left branch of coronary artery in
      cardiogenic shock complicating myocardial infarction of anterior and side heart
      wall].

PMID- 17206549
TI  - [Morgagni-Adams-Stokes after adenosine injection in a patient with WPW syndrome-
      a case report].
AB  - A case of a 16-year-old girl with left sided accessory pathway is presented.
      Following adenosine-induced termination of atrio-ventricular reentrant
      tachycardia the patient developed polymorphic ventricular tachycardia followed by
      preexcited atrial fibrillation with very rapid ventricular response and syncope.
      Arrhythmia was terminated by amiodarone infusion. Potential complications after
      adenosine injection are discussed.

PMID- 17206550
TI  - [Commentary to the articles: SPACE Collaborative Group. 30 day results from the
      SPACE trial of stent-protected angioplasty versus carotid endarterectomy in
      symptomatic patients: a randomised non-inferiority trial. Lancet 2006; 368: 1239
      47. Mas JL, Chatellier G, Beyssen B, et al. EVA-3S Investigators. Endarterectomy
      versus stenting in patients with symptomatic severe carotid stenosis. N Engl J
      Med. 2006; 355: 1660-71].

PMID- 17206551
TI  - [New Guidelines in the selection of patients with heart insufficiency for heart
      transplantation - discussion of standards of the International Society of Heart
      and Lung Transplantation (ISHLT) in 2006].

PMID- 17206552
TI  - [Monitored and spontaneous cardiac rehabilitation in the home environment as an
      alternative to traditional ambulatory rehabilitation].

PMID- 17206553
TI  - [Intrauterine fetal death in pregnancies of women with preconceptional and
      gestational diabetes mellitus and of women without glucose tolerance disorders.
      Results of the perinatal registry of Lower Saxony, Germany].
AB  - OBJECT: The prevalence of intrauterine fetal death as well as the relevant risk
      factors in pregnancies of women with preconceptional and gestational diabetes
      mellitus and non-diabetic women were investigated. METHODS: The data of the
      Perinatal Registry of Lower Saxony between 1987 and 1999 for pregnancies of women
      with preconceptional diabetes mellitus (PDM, n = 3351), gestational diabetes
      mellitus (GDM, n = 3954) and women without diabetes mellitus (non-diabetic
      pregnancies, NDM, n = 887,779) were retrospectively analysed. RESULTS:
      Intrauterine fetal death occurred in 46 women with PDM (1.35 %), 32 women with
      GDM (0.79 %) and 2756 non-diabetic women (0.31 %). The odds ratio (OR, 95 % CI)
      for PDM vs. NDM was 4.468 (3.332 - 5.992; p < 0.01) and for GDM vs. NDM it was
      2.595 (1.829 - 3.682; p < 0.01). The percentage of death, which occurs before the
      32nd week of gestation, was 13 % in pregnancies with PDM, 12.5 % in pregnancies
      with GDM and 27.7 % in non-diabetic pregnancies. 50 % of fetal deaths in the PDM
      group, 43.8 % of those in the GDM group and 39.3 % of those in the NDM group
      occurred after the 36th week of gestation. The percentages of dead fetuses who
      were under the 10th percentile of growth (small for gestational age, SGA), in
      pregnancies with PDM, GDM and NDM were 15.2 %, 6.3 %, and 28.7 %, respectively.
      The percentages of dead fetuses above the 90th percentile of growth (large for
      gestational age, LGA) were 41.3 % (PDM), 37.5 % (GDM), and 8.7 % (NDM), (p < 0.01
      for PDM vs. NDM and for GDM vs. NDM). CONCLUSION: The risk of intrauterine fetal
      death in pregnancies of diabetic women is still increased. It seems that
      especially the LGA fetuses of diabetic mothers and SGA fetuses of non-diabetic
      mothers are at greater risk of intrauterine death.

PMID- 17206554
TI  - [Perinatal morbidity in pregnancies of women with preconceptional and gestational
      diabetes mellitus in comparison with pregnancies of non-diabetic women. Results
      of the perinatal registry of Lower Saxony, Germany].
AB  - OBJECTIVE: Pregnancies of women with glucose tolerance disorders are still
      associated with high maternal and perinatal morbidity. In the present population
      based study, we investigated the fetal and neonatal risks and complications in
      pregnancies of women with preconceptional and gestational diabetes in comparison
      with pregnancies of non-diabetic women. METHODS: A total of 913,255 pregnancies
      with 926,685 newborns documented by the Perinatal Registry of Lower Saxony,
      Germany, between 1987 and 1999 was retrospectively evaluated. In particular, the
      obstetric parameters of 3439 women with preconceptional diabetes mellitus (PDM, n
      = 3485 neonates), 4051 women with gestational diabetes mellitus (GDM, n = 4155
      neonates) and 905,765 non-diabetic women (NDM, n = 919.053 neonates) were
      analysed. RESULTS: The diabetes groups had a higher rate of preterm birth < 31st
      week of gestation (PDM vs. NDM odds ratio [OR] 2.341; GDM vs. NDM OR 1.483) and
      between the 32nd and 37th weeks of gestation (OR 3.688 and 2.418, respectively).
      The incidences of pathological cardiotocograms (OR 1.519 and 1.258, respectively)
      and acidosis as indication for operative delivery (OR 5,015 and 2,102,
      respectively) were increased in the diabetes groups. There was a higher
      prevalence of birth weight > 4500 g (OR 2.775 and 2.742, respectively) and >95.
      percentile (OR 4.268 and 3.610, respectively) in newborns of diabetic women. The
      higher rate of umbilical arterial pH < 7.00 (OR 2.481 and 1.195, respectively) as
      well as Apgar score at 1 minute <7 (OR 2.971 and 1.897, respectively) indicated a
      poorer neonatal outcome in pregnancies of women with diabetes mellitus. The
      frequency of necessary intubation of the infants was significantly higher in the
      diabetes group (OR 3.384 and 1.317, respectively). There also was an increased
      prevalence of intrauterine fetal death in pregnancies of diabetic women (OR 4.197
      and 2.511, respectively). CONCLUSION: Pregnancies of women with diabetes mellitus
      are still correlated with higher perinatal risks and complications. The neonatal
      morbidity in pregnancies with gestational diabetes mellitus was more similar to
      that of pregnancies with preconceptional diabetes mellitus than to the morbidity
      in the group of non-diabetic women. Changes of the parameters within the
      observation period were the same in all three groups and therefore cannot be
      attributed to a primary more intensive prenatal care of diabetic women.

PMID- 17206555
TI  - [Origin and significance of leptin and neuropeptide Y (NPY) in amniotic fluid
      between the 14th and 18th weeks of gestation].
AB  - INTRODUCTION: Leptin and neuropeptide Y (NPY) play important roles in the
      regulation of food intake, energy expenditure, hematopoesis and reproduction. The
      biological functions of leptin and NPY in fetal development, and their regulation
      during pregnancy by fetal and maternal factors remain poorly understood. PATIENTS
      AND METHODS: From 55 women undergoing diagnostic amniocentesis between the 14th
      and 18th weeks of gestation samples of amniotic fluid were collected. In accord
      with the circadian rhythm of leptin secretion all amniocenteses were performed
      between 8.00 and 12.00 a. m. The concentrations of leptin and NPY in amniotic
      fluid were analysed using commercially available RIA's. RESULTS: The amniotic
      fluid samples of 32 male and 23 female fetuses were determined and demonstrated
      no gender-dependent differences in leptin and NPY levels. No correlation was
      found between leptin/NPY and the maternal body mass index. NPY concentrations are
      lower in advanced gestational age pregnancies. Leptin levels revealed no
      differences with respect to gestational age. CONCLUSION: Leptin and NPY levels
      were independent of fetal gender and maternal BMI. This provides clues for
      alternative regulatory mechanisms in leptin and NPY secretion. Compared to the
      data of adults, our findings show high leptin concentrations in the amniotic
      fluid in the presence of only minor amounts of white adipose tissues which might
      include the placenta. Our data including the observation of lower levels of NPY
      in more advanced gestational age support the idea of specific factors regulating
      leptin and NPY secretion into the amniotic fluid.

PMID- 17206556
TI  - [Neonatal septicemia in the G-DRG system].
AB  - INTRODUCTION: The introduction of Diagnosis Related Groups in Germany (G-DRG) has
      brought forward the obligation for physicians to take into account an intricate
      system of medical, economical and legal implementations. Mistakes in the process
      of encoding the principal diagnosis or procedures may have financial
      consequences. Problems to determine the correct ICD-code will be most prominent
      for diseases with poorly defined or even inconsistent diagnostic criteria as is
      the case for neonatal septicemia. We decided to evaluate whether the introduction
      of G-DRG resulted in a change of frequency of the diagnosis "neonatal
      septicemia". METHODS: We analysed data derived from the quality assurance program
      "Neonatalerhebung" in the state of Baden-Wurttemberg during the years of 2001
      through 2004, i. e., 2 years before and 2 years during the introduction of G-DRG.
      During this period an annual number of 12,316 up to 13,172 newborns were admitted
      to the participating hospitals. RESULTS: The mean number of diagnoses per patient
      increased from 2.2 to 3.8. The frequency of the diagnosis of septicemia remained
      constant. The percentage of newborns receiving antibiotic therapy did not change.
      The ratio of cases with "septicemia yes" over "antibiotics yes" did not change.
      Although it is difficult to determine the diagnosis of neonatal septicemia and in
      spite of the economic implications of this diagnosis, no change in the frequency
      of this diagnosis occurred during the introduction of DRG. CONCLUSIONS: Assuming
      that the participating hospitals used an identical database for the quality
      assurance program "Neonatalerhebung" and for accounting, we conclude that the DRG
      system is stable with respect to neonatal septicemia.

PMID- 17206557
TI  - [Pasteurella multocida as a rare cause of neonatal meningitis].
AB  - Pasteurella multocida (P. multocida), a Gram-negative bacillus is a typical
      commensal in the oropharynx of animals such as dogs and cats. Human diseases
      caused by P. multocida are rare and include respiratory infections, sepsis and
      meningitis. P. multocida infections are described predominantly in patients with
      underlying chronic disorders, in elderly patients or in infants < or = 1 year. We
      describe the case of a 3-week-old boy with meningitis due to Pasteurella
      multocida. P. multocida was also identified in oral swab and stool cultures of
      the pet cat. A direct contact between baby and cat was negated by the parents.
      The patient recovered without any neurological sequelae.

PMID- 17206558
TI  - [Congenital skin lesions in occult spinal dysraphism--what is typical?].
AB  - Occult spinal dysraphism (OSD) includes a group of spinal malformations covered
      by intact skin. Neurological sequelae include paresis and sensory deficits in the
      lower limbs, neurogenic bladder and bowel disturbances, pain and neuro
      orthopaedic syndrome as well as a high risk for secondary neurological
      deterioration. In up to 80 % of the cases, OSD is accompanied by lumbosacral skin
      anomalies. In this article, an overview on the main forms of OSD and
      characteristic skin lesions is given, which can guide the clinician to early
      diagnosis and appropriate diagnostic work-up and, if necessary, therapeutic
      intervention.

PMID- 17206559
TI  - Protective effect of glycyrrhizin, glycyrrhetic acid and matrine on acute
      cholestasis induced by alpha-naphthyl isothiocyanate in rats.
AB  - Alpha-naphthyl isothiocyanate (ANIT) is a known hepatotoxicant that causes acute
      cholestatic hepatitis characterized by the infiltration of neutrophils around
      bile ducts and necrotic hepatocytes. The effects of glycyrrhizin (GL), 18beta
      glycyrrhetinic acid (GA), matrine (MT), oxymatrine (OMT), salvianolic acid B
      (SAB), silymarin (SI) and dexamethasone (DEX) on ANIT-induced acute cholestasis
      in rats were investigated. Serological and histological data demonstrated that
      the administration of GL, GA or MT all protected against hepatocyte injury and
      cholestasis induced by ANIT. Furthermore, the bile flow and the accumulative bile
      excretion of ketoprofen glucuronide (KPG), that were significantly suppressed by
      ANIT, were preserved in rats administered GL, GA or MT. DEX protected against
      acute cholestasis but did not protect against hepatocyte necrosis and elevated
      serum alanine aminotransferase levels following ANIT administration. Rats
      administrated OMT, SAB or SI were not resistant to ANIT toxicity. In summary, the
      protective effect of DEX is directed toward cholangiocytes rather than
      hepatocytes whereas the natural products, GA, GL and MT, exhibit significantly
      better protective effects against ANIT-induced liver damage including the
      protection of hepatocytes as well as cholangiocytes.

PMID- 17206560
TI  - [Surgical principles in the treatment of diverticular disease].

PMID- 17206561
TI  - [Intraoperative neuromonitoring of the recurrent laryngeal nerve - results and
      learning curve].
AB  - Intraoperative neuromonitoring was introduced in thyroid surgery several years
      ago resulting in a facilitated identification of the recurrent laryngeal nerve
      and less recurrent laryngeal nerve injuries. Between 1999 and 2004 data of all
      patients (n=937) undergoing thyroid resection were recorded prospectively and
      analyzed yearly. The intraoperative identification of recurrent laryngeal nerve
      succeeded in 99.2% (1665 nerves at risk). The percentage of completely resecting
      surgical procedures raised from 17% to 56%. Minimal vocal cord dysfunction
      associated with hematoma and edema in most cases was diagnosed laryngosopically
      in 1.4-2.4%. Transient recurrent nerve palsies were seen in 2.3% without changes
      throughout the years. The permanent palsy rate of 0.8% in the first years
      decreased. No permanent palsies were diagnosed in the last 3 years. Routine
      introduction of intraoperative neuromonitoring in thyroid surgery is associated
      with a demonstrable learning curve lasting several years. Permanent palsy rate is
      decreased. The rate of minimal vocal cord movement disorders and transient
      recurrent laryngeal nerve palsies is not changed.

PMID- 17206562
TI  - [Rectusbanding variation II - a method for the repair of incisional hernias -
      further developments].
AB  - We report on further developments of the rectusbanding variation II method which
      is used for the repair of large incisional hernias in 70 patients. Using this
      method the musculus rectus abdominis is not entirely looped. Instead, the
      polypropylene bands, which have been placed in sublay position, are penetrating
      the lateral rim through incisions and are fastened there. Important to note that
      the polypropylene bands are not used to ligate the abdominal wall. The bands must
      be placed loosely. This allowed us to reduce the applied material by almost 50
      per cent. Although a high number (n = 70) of large incisional hernias (about 150
      cm (2), variation I n = 16/20,3%, variation II n = 29/41,4%) were operated upon
      with this method (rectusbanding variation II) previous excellent results could be
      further improved (wound infectionrate 2,8%, recurrence rate after 18 months 0%,
      patients had no complaints and their mobility was excellent). Only the seroma
      formation rate was slightly increased due to the large size of the hernias. These
      excellent results are mainly based on the absolutely reliable fixing of the
      polypropylene bands and the complete mesh coverage by soft tissue. This method
      can be easily learned by any surgeon and is a true alternative to all
      conventional methods which have been published so far. In particular laparoscopic
      methods for incisional hernia repair can be replaced by this technique.

PMID- 17206563
TI  - [Therapy and course of disease in spontaneous esophageal perforations].
AB  - INTRODUCTION: Esophageal perforations occur spontaneously or as a complication of
      endoscopic procedures. Especially in spontaneous perforation there is ongoing
      debate regarding the best treatment options. METHODS: 24 patients that were
      treated at two surgical centers (University Halle, City-hospital Bielefeld) after
      spontaneous esophageal perforations between 1996 and 2005 were analysed
      retrospectively. RESULTS: All patients but one underwent surgical treatment with
      in 2 cases additional stent implantation. Average stay in hospital was 53 days.
      In-hospital-lethality was 25% (overall lethality 37.5%). Concerning the
      therapeutic outcome there was no link between patients' age, localization or size
      of the perforation and the time interval between perforation and treatment. In 22
      patients diagnosis was made > 12hrs after the event. CONCLUSIONS: Main problem of
      the Boerhaave-syndrome is the septic-toxic disease. Prognostic criteria are the
      patients' health-state and not factors like size of perforation, time of delay or
      localization of the perforation. Since in case of survival esophageal resection
      shows good long-term-results, in doubt a radical surgical procedure should be
      recommended as primary option. Implanting an esophageal stent might become a
      useful mean of treating patients with spontaneous perforations.

PMID- 17206564
TI  - [Prevention of bile duct injuries after laparoscopic cholecystectomy. "The
      critical view of safety"].
AB  - INTRODUCTION: Iatrogenic injuries of the bile duct and hepatic artery represent a
      continuous problem after laparoscopic cholecystectomy. In this observational
      study we report about our experiences applying the "critical view of safety",
      defined as unambiguous identification of the cystic duct and artery by creation
      of an infundibular window, in order to minimise bile duct lesions and conversion
      rate. METHODS: Between July 2002 and November 2004 100 consecutive laparoscopicly
      started cholecystectomies were prospectively investigated. The central surgical
      step of dissection aimed at reaching the "critical view of safety" and its photo
      printing before cutting the cystic duct and artery, otherwise a conversion was
      carried out without exception. Primary endpoints of the study were the conversion
      rate, secondary endpoints the incidence of intra- and postoperative
      complications, operation time and histological results. RESULTS: 53 of the 100
      primary laparoscopic operated patients showed the signs of an acute
      cholecystitis, 44 patients offered partially multiple abdominal operations in
      their history. In 19 patients we performed a "therapeutic splitting". Only in 3
      patients it was not possible to apply the "critical view of safety" resulting in
      a conversion to open cholecystectomy. The mean operation time was 81 minutes and
      the postoperative hospital stay ranged to 5.4 (1-18) days. Postoperatively an
      insufficiency of cystic duct, a navel infection, an abdominal wall haematoma, an
      urinary tract infection and a pneumonia occurred in one patient each. DISCUSSION:
      Pivotal factors leading to bile duct injury after laparoscopic cholecystectomy
      are systematic mistakes in the surgical technique, an insufficient surgical
      training and human failure of the surgeon. The introduction of the "critical view
      of safety" represents an objective, understandable and compulsory criterion for
      minimising the risk of iatrogenic injuries of the bile duct and decision on
      conversion to open cholecystectomy.

PMID- 17206565
TI  - [Extent of lymphnode dissection with minimally invasive esophageal resection].
AB  - Esophageal resection is still today associated with a high morbidity and
      mortality. Minimally invasive procedures show a significantly lower rate of such
      complications and therefore might also be associated with a lower surgical risk.
      However, publications till date contain little or no data on the extent of lymph
      node dissection. The aim of our study was to evaluate the morbidity and mortality
      rate of minimally invasive esophageal resection. MATERIAL AND METHODS: In the
      last two years, we carried out 25 minimally invasive esophageal resections on
      five women and 20 men with a median age of 63 years (range 41-74 years). All data
      were accrued prospectively. RESULTS: Nine patients were operated upon
      transhiatally and 12 combined laparocopic-thoracoscopic. On four patients, a
      thoracotomy was necessary. The average surgical time for the transhiatal approach
      was calculated at 164 minutes (range 150-180 min) and for the combined
      laparoscopic-thoracoscopic procedure 285 minutes (240-360 min). The thoracoscopic
      esophageal resection itself lasted 105 minutes on average; the last five
      resections each lasting 70 minutes. A median of 24,5 lymph nodes (19-26) was
      calculated in the laparoscopic-thoracoscopic technique. The transhiatal procedure
      revealed a median of 14 lymph nodes (12-17). Postoperatively, we had three cases
      of anastomotic and two cases of bronchial leakages, most probably associated with
      the use of monopolar current; complications no longer seen since usage of the
      HARMONIC ACE for surgical preparation. There was no 30 day letality. CONCLUSION:
      Our experience with 25 successful minimally invasive esophageal resections shows
      that with increasing experience and better surgical equipment, the extent of
      lymph node dissection does not differ from open procedure.

PMID- 17206566
TI  - [Need and extension of lymph node dissection in gallbladder carcinoma].
AB  - Gallbladder carcinomas have the propensity to metastasize early, commonly into
      locoregional lymph nodes. For gallbladder carcinomas with infiltration of at
      least the muscularis (pT1b) or subserosa (pT2), surgical therapy with a curative
      intent always includes a locoregional lymphadenectomy besides cholecystectomy and
      an anatomical or atypical liver resection. In incidentally discovered gallbladder
      carcinomas, such a locoregional lymphadenectomy should be performed depending on
      the age of the patient and on tumor extension. However, this only is helpful with
      respect to prognosis, if the metastases are limited to the hepatoduodenal
      ligament or to the posterosuperior pancreaticoduodenal nodes. For gallbladder
      carcinomas with metastases into more distal lymph nodes, especially in paraaortal
      nodes, lymphadenectomy only rarely impacts long-term survival. An extended
      lymphadenectomy that includes resection of the bile duct and/or pancreatic head
      is associated with an increased rate of morbidity and mortality, therefore not
      being of proven advantage in terms of prognosis.

PMID- 17206567
TI  - [Results and significance of lymphadenectomy in pancreatic cancer].
AB  - Pancreatic adenocarcinoma is one of the most aggressive human solid tumors with a
      5-year survival rate of less than 5%. The only chance for cure is complete
      resection of the tumor. This can be achieved in approximately 8-15% of all cases
      since solely localized tumors and a small part of locally advanced carcinomas may
      be resected. However, many patients suffer from a local relapse after surgical
      therapy. In order to improve the long-term survival of surgically treated
      patients, extended lymphadenectomy after partial duodenopancreatectomy was
      introduced. Some retrospective studies from the 80 s showed improved survival
      rates for those patients in whom extended lymphadenectomy was performed. However,
      these results were not confirmed in following randomised controlled prospective
      studies. Extended lymphadenectomy can be performed with slightly increased
      morbidity and equal mortality but survival is not improved. Therefore, standard
      lymphadenectomy is recommended in patients undergoing duodenopancreatectomy for
      pancreatic cancer. Extended lymphadenectomy (with retroperitoneal clearance)
      should only be accomplished within controlled clinical studies.

PMID- 17206568
TI  - [Are there relevant minimum procedure volumes in trauma and orthopedic surgery?].
AB  - INTRODUCTION: The introduction of minimum surgical volumes aimed at improving the
      quality of care is currently the subject of controversial debate. One relevant
      issue is whether the data from external quality assurance can be used to predict
      outcomes that justify the introduction of minimum surgical volumes. METHOD:
      Analysis was carried out on the procedures total knee replacements
      (arthroplasties) (TKA) and femoral neck fractures (FNF). A total of 31,657 data
      records from North Rhine Westphalia (2002/2003) were included in TKA evaluation.
      The data records provided by the External Quality Assurance Department of the
      General Medical Council, Westphalia Lippe (from 1993 to 2000) were merged with
      data compiled between 2001 and 2004 by the German National Quality Assurance
      Center (BQS) in a survey conducted in North Rhine Westphalia. A total of 49,928
      cases were analyzed. The analysis aimed to determine any connections between
      number of cases and outcome quality. RESULTS: No connection between outcome
      quality and number of cases was postulated for TKA in terms of general
      complications such as cardiovascular events, pneumonia, pulmonary embolism and
      thrombosis. By contrast, the incidence of specific complications secondary to TKA
      (wound infections, abscesses, hematomas and postoperative bleeding) was much
      rarer in hospitals with high case volumes. The trend noted in the overall group
      may appear a contrary one when the individual departments and hospitals are
      considered. No connection was established for FNF outcomes. DISCUSSION: In line
      with reports in the literature, it can be presumed that a connection exists
      between outcome quality and surgical volume for TKA. However, no threshold value
      can be deduced on the basis of current outcome data. Debate continues as to
      whether the introduction of minimum surgical volumes might be economically
      motivated and how minimum surgical volumes might impact healthcare structures.
      Lastly, it is discussed whether or not diagnostic related groups (DRG) inherently
      lead to a concentration of services that would make the introduction of minimum
      surgical volumes superfluous.

PMID- 17206569
TI  - [The "new" Erlangen technique of funnel chest correction - minimalization of a
      well working procedure].
AB  - INTRODUCTION: In many operative fields there is a trend to be minimally invasive,
      so in chestwall surgery too. Because of this influence we developed a technique
      for routine measurements of the forces during surgery. So it was possible to make
      the Erlangen technique substantially less invasive. METHODS: Mobilisation of the
      sternum always begins with freeing of the xiphisternum. Then we use a spring
      balance with a measurement range of 20-230 N. This is attached to the sternum
      with a single-pronged hook, and then the sternum is raised to the desired
      position. DISCUSSION: Since the introduction of intraoperative measurements it
      has been possible to make the Erlangen technique substantially less invasive,
      i.e. division of the ribs at the outer rim of the funnel, previously always
      carried out, is no longer done. Of course we could also minimise the length of
      the incision.

PMID- 17206570
TI  - [Plastic reconstruction of postoncologic defects in the pelvic area].
AB  - The surgical management of defects in the pelvic region is a great surgical
      challenge. Primary tumor recurrences have to be addressed and local infections
      require appropriate therapy such as rigorous debridement and antibiotic therapy.
      Plastic surgery provides tissue reconstruction by well perfused flaps and also
      reestablishment of anatomic structures in the ano-genital region. An early
      reconstruction also reduces the wound complications of adjuvant or post oncologic
      therapy and reduces the rate of wound healing problems.

PMID- 17206571
TI  - [Recent findings in minor traumatic brain injury in sports].

PMID- 17206572
TI  - [Treatment of burn victims: who can be treated as an outpatient and who requires
      treatment as an inpatient?].

PMID- 17206573
TI  - Implantation of cryopreserved mitral allograft into the tricuspid position in an
      experimental study in sheep: technical aspects of implantation and immediate
      results evaluated by epicardial echocardiography.
AB  - AIMS: Cryopreserved mitral allograft valve (MAV) offers theoretical advantages
      over conventional mechanical or biological prostheses in tricuspid position,
      especially in infectious endocarditis patients. MAV processing and tricuspid
      valve (TV) replacement in a sheep model is described. METHODS AND RESULTS: In 20
      adult sheep, MAV were harvested, processed and cryopreserved. One month later,
      recipient's TV were excised and the MAVs were transplanted into the tricuspid
      position in 13 sheep, under general anaesthesia, via a right thoracotomy, with an
      extracorporeal circulation (ECC) and cardioplegic heart arrest. Both MAV
      papillary muscles were anchored into the right ventricular wall by transmural
      stitches and the MAV anulus was sewn into the recipient's tricuspid anulus. After
      weaning from ECC, the anatomy and function of the MAV in the tricuspid position
      was assessed by epicardial echocardiography. The average duration of the ECC was
      58 minutes (42-88), the cardioplegic heart arrest was 36 minutes (28-45). Weaning
      from EEC was always uneventful. Right atrial & pulmonary artery pressure
      measurements and epicardial echocardiography documented good function of all
      MAVs. CONCLUSION: MAV remained mechanically strong enough for implantation into
      the tricuspid position. Reproducible technique of MAV transplantation into the
      tricuspid position with excellent early postoperative haemodynamic performance
      was developed.

PMID- 17206574
TI  - [Melorheostosis of the foot: a case report of a rare entity].
AB  - INTRODUCTION: Melorheostosis is a rare bony dysplasia and often recognised just
      sporadically by chance. CASE REPORT: We present a case of a 15 year old girl who
      presented a melorheostosis of the left foot. After birth there was recognized a
      shortening and deformity of the 2nd toe on the left foot. Furthermore she had an
      interphalangeal hallux valgus that displaced the 2nd toe increasingly. Thus in
      the last years there were more and more difficulties to wear normal shoes.
      Conservative therapy was not successful. We performed a lengthening extending
      osteotomy of the 2nd toe (a modified Weil osteotomy) and an Akin osteotomy of the
      interphalangeal hallux valgus. Since the surgical procedure the patient is out of
      any complaints. DISCUSSION: We demonstrate the radiologic and histologic findings
      and discuss the relevant literature and possible etiology.

PMID- 17206575
TI  - [Perforated jejunal divertikula - a rare differential diagnosis of acute
      abdominal pain].
AB  - DIAGNOSTIC FINDINGS: We report about a 83 years old female with persisting
      abdominal pain for 3 days. Abdominal x-ray, as well as abdominal ultrasound
      examination were unsuccessful. CT scan revealed a 7 cm tumor, suspicious for
      abscess. OPERATION: Diagnostic laparotomy showed a 6 cm inflammatory tumor with
      covered perforation of a jejunal diverticula at the 4th intestinal loop distal
      the ligament of Treitz. We performed a segmental resection. FOLLOW UP: Clinical
      follow-up was uneventful, the patient was without any symptoms within the first 6
      months. Pre- and intraoperative pathology will be explained and discussed
      referring to the literature.

PMID- 17206576
TI  - [Jural - decisions and background].

PMID- 17206577
TI  - Ecological specialization and adaptive decay in digital organisms.
AB  - The transition from generalist to specialist may entail the loss of unused traits
      or abilities, resulting in narrow niche breadth. Here we examine the process of
      specialization in digital organisms--self-replicating computer programs that
      mutate, adapt, and evolve. Digital organisms obtain energy by performing
      computations with numbers they input from their environment. We examined the
      evolutionary trajectory of generalist organisms in an ecologically narrow
      environment, where only a single computation yielded energy. We determined the
      extent to which improvements in this one function were associated with losses of
      other functions, leading to organisms that were highly specialized to perform
      only one or a few functions. Our results show that as organisms evolved improved
      performance of the selected function, they often lost the ability to perform
      other computations, and these losses resulted most often from the accumulation of
      neutral and deleterious mutations. Beneficial mutations, although relatively
      rare, were disproportionately likely to cause losses of function, indicating that
      antagonistic pleiotropy contributed significantly to niche breadth reductions in
      this system. Occasionally, unused functions were not lost and even increased in
      performance. Here we find that understanding how the functions were integrated
      into the genome was crucial to predictions of their maintenance.

PMID- 17206578
TI  - Habitat connectivity and ecosystem productivity: implications from a simple
      model.
AB  - The import of resources (food, nutrients) sustains biological production and food
      webs in resource-limited habitats. Resource export from donor habitats subsidizes
      production in recipient habitats, but the ecosystem-scale consequences of
      resource translocation are generally unknown. Here, I use a nutrient
      phytoplankton-zooplankton model to show how dispersive connectivity between a
      shallow autotrophic habitat and a deep heterotrophic pelagic habitat can amplify
      overall system production in metazoan food webs. This result derives from the
      finite capacity of suspension feeders to capture and assimilate food particles:
      excess primary production in closed autotrophic habitats cannot be assimilated by
      consumers; however, if excess phytoplankton production is exported to food
      limited heterotrophic habitats, it can be assimilated by zooplankton to support
      additional secondary production. Transport of regenerated nutrients from
      heterotrophic to autotrophic habitats sustains higher system primary production.
      These simulation results imply that the ecosystem-scale efficiency of nutrient
      transformation into metazoan biomass can be constrained by the rate of resource
      exchange across habitats and that it is optimized when the transport rate matches
      the growth rate of primary producers. Slower transport (i.e., reduced
      connectivity) leads to nutrient limitation of primary production in autotrophic
      habitats and food limitation of secondary production in heterotrophic habitats.
      Habitat fragmentation can therefore impose energetic constraints on the carrying
      capacity of aquatic ecosystems. The outcomes of ecosystem restoration through
      habitat creation will be determined by both functions provided by newly created
      aquatic habitats and the rates of hydraulic connectivity between them.

PMID- 17206579
TI  - Uncovering the biodiversity of genetic and reproductive systems: time for a more
      open approach. American Society of Naturalists E. O. Wilson Award winner address.
AB  - Important scientific findings frequently arise from serendipitous findings.
      Unfortunately, many scientists are not prepared to take advantage of unexpected
      results and to question established paradigms, and this prevents them from
      capitalizing on their good fortune. In this essay, I first explain how pure
      serendipity led us to discover unusual modes of reproduction such as clonal
      reproduction by males and a green-beard gene. Next, I argue that the reproductive
      systems of ants and other organisms are probably much more diverse than is
      generally appreciated. This leads me to advocate for a new "molecular naturalist"
      approach to reproductive systems and a more "naturalistic" approach in population
      and evolutionary genetics. Finally, I make two further points. The first is that
      our current funding and education systems tend to hinder originality and
      curiosity. The other is that the field of ecology and evolution, and more
      generally all of science, would benefit from a shift in values from scientific
      productivity to scientific creativity. A few suggestions are made to this effect.

PMID- 17206580
TI  - The evolution of condition-dependent sexual dimorphism.
AB  - Theory suggests that the net benefit of allocating resources to a sexual trait
      depends both on the strength of sexual selection on that trait and on individual
      condition. This predicts a tight coevolution between sexual dimorphism and
      condition dependence and suggests that these patterns of within-sex and between
      sex variation may share a common genetic and developmental basis. Although
      condition-dependent expression of sexual traits is widely documented, the extent
      of covariation between condition dependence and sexual dimorphism remains poorly
      known. I investigated the effects of condition (larval diet quality) on
      multivariate sexual dimorphism in the fly Telostylinus angusticollis (Neriidae).
      Condition determined the direction of sexual size dimorphism and modulated sexual
      shape dimorphism by affecting allometric slopes and/or intercepts of sexually
      homologous traits in both sexes. Although the greatest responses to condition
      manipulation were observed in male sexual traits, both sexual and nonsexual
      traits exhibited substantial variation in the nature and magnitude of condition
      effects. Nonetheless, condition dependence and sexual dimorphism were remarkably
      congruent: variation in the strength of condition effects on male traits
      explained more than 90% of the variation in the magnitude of sexual dimorphism,
      whether quantified in terms of trait size or allometric slope. The genetic
      mechanisms that give rise to multivariate sexual dimorphism in body shape thus
      function in a strongly condition-dependent manner in this species, suggesting a
      common genetic basis for body shape variation within and between sexes.

PMID- 17206581
TI  - Sexual systems and measures of occupancy and abundance in an annual plant:
      testing the metapopulation model.
AB  - The need for reproductive assurance during dispersal, along with the pressure of
      local mate competition, means that the importance of frequent or repeated
      colonization is implicit in the sexual-system evolution literature. However, to
      date there have been few empirical tests of the association between colonization
      and the sexual system in plants. Here we provide such a test by comparing
      occupancy and abundance of populations of the European plant Mercurialis annua
      across regions characterized by different sexual systems. Specifically, we
      predicted that monomorphic, hermaphroditic populations, which are thought to have
      evolved under selection for reproductive assurance during repeated bouts of
      colonization, would be smaller and their suitable habitat less frequently
      occupied than dimorphic populations, where males co-occur with either females or
      hermaphrodites. We show that both of these predictions are upheld. We evaluate
      our results against competing hypotheses for the occupancy-abundance relationship
      and conclude that they are most consistent with the metapopulation model for
      sexual-system variation in M. annua.

PMID- 17206582
TI  - An evolutionary cost of separate genders revealed by male-limited evolution.
AB  - Theory predicts that intralocus sexual conflict can constrain the evolution of
      sexual dimorphism, preventing each sex from independently maximizing its fitness.
      To test this idea, we limited genome-wide gene expression to males in four
      replicate Drosophila melanogaster populations, removing female-specific
      selection. Over 25 generations, male fitness increased markedly, as sexually
      dimorphic traits evolved in the male direction. When male-evolved genomes were
      expressed in females, their fitness displayed a nearly symmetrical decrease.
      These results suggest that intralocus conflict strongly limits sex-specific
      adaptation, promoting the maintenance of genetic variation for fitness.
      Populations may carry a heavy genetic load as a result of selection for separate
      genders.

PMID- 17206583
TI  - The loss of adaptive plasticity during long periods of environmental stasis.
AB  - Adaptive plasticity allows populations to adjust rapidly to environmental change.
      If this is useful only rarely, plasticity may undergo mutational degradation and
      be lost from a population. We consider a population of constant size N undergoing
      loss of plasticity at functional mutation rate m and with selective advantage s
      associated with loss. Environmental change events occur at rate theta per
      generation, killing all individuals that lack plasticity. The expected time until
      loss of plasticity in a fluctuating environment is always at least tau, the
      expected time until loss of plasticity in a static environment. When mN > 1 and N
      theta >> 1, we find that plasticity will be maintained for an average of at least
      10(8) generations in a single population, provided tau > 18/theta. In a
      metapopulation, plasticity is retained under the more lenient condition tau >
      1.3/theta, irrespective of mN, for a modest number of demes. We calculate both
      exact and approximate solutions for tau and find that it is linearly dependent
      only on the logarithm of N, and so, surprisingly, both the population size and
      the number of demes in the metapopulation make little difference to the retention
      of plasticity. Instead, tau is dominated by the term 1/(m+s/2).

PMID- 17206584
TI  - Age-specific fitness components and their temporal variation in the barn owl.
AB  - Theory predicts that temporal variability plays an important role in the
      evolution of life histories, but empirical studies evaluating this prediction are
      rare. In constant environments, fitness can be measured by the population growth
      rate lambda, and the sensitivity of lambda to changes in fitness components
      estimates selection on these traits. In variable environments, fitness is
      measured by the stochastic growth rate lambda(S), and stochastic sensitivities
      estimate selection pressure. Here we examine age-specific schedules for
      reproduction and survival in a barn owl population (Tyto alba). We estimated how
      temporal variability affected fitness and selection, accounting for sampling
      variance. Despite large sample sizes of old individuals, we found no strong
      evidence for senescence. The most variable fitness components were associated
      with reproduction. Survival was less variable. Stochastic simulations showed that
      the observed variation decreased fitness by about 30%, but the sensitivities of
      lambda and lambda(S) to changes in all fitness components were almost equal,
      suggesting that temporal variation had negligible effects on selection. We
      obtained these results despite high observed variability in the fitness
      components and relatively short generation time of the study organism, a
      situation in which temporal variability should be particularly important for
      natural selection and early senescence is expected.

PMID- 17206585
TI  - On the relationship between productivity and food chain length at different
      ecological levels.
AB  - The effects of energy on food web structure have been debated for at least 80
      years. Nevertheless, the empirical evidence is meager, especially from
      terrestrial ecosystems. We analyzed long-term temporal variation in food chain
      length in a semiarid continental ecosystem, where productivity shows large
      interannual variations. Incidence of nonherbivorous prey in predator diet was
      used as a proxy of trophic position, allowing us to analyze the effect of
      productivity on food chain length within the assemblage of top predators (which
      comprises the most abundant and persistent top predators in the system) and to
      compare observed patterns at the species and assemblage levels. At the species
      level, the relationship between trophic position and productivity took different
      forms, varying in magnitude and shape. This pattern contrasts with the consistent
      increase in food chain length, with productivity observed at the assemblage
      level. Our results indicate that productivity can be a main determinant of food
      chain length, but not necessarily because of energy limitation. Further, the
      increase in food chain length with available energy probably represents an
      aggregate attribute, driven to a large extent by predators with higher
      consumption rates, rather than being the result of compensatory responses among
      predators.

PMID- 17206586
TI  - Parental effort and reproductive skew in coalitions of brood rearing female
      common eiders.
AB  - Members of breeding groups face conflicts over parental effort when balancing
      antipredatory vigilance and feeding. Empirical evidence has shown disparate
      responses to manipulations of parental effort. We develop a model in which we
      determine the evolutionarily stable effort of partners given their body
      conditions, allowing the benefits of shared care to be unevenly divided, and we
      test this model's predictions with data on common eiders (Somateria mollissima).
      Eiders show uniparental female care; females may share brood rearing, or they may
      tend alone, and their body condition at hatching of the young shows large
      environmentally induced variation. The model predicts that parental effort
      (vigilance) in a coalition is lower than when tending alone, controlling for
      parental condition; this prediction is supported by the data. The parental effort
      in a coalition should be positively correlated with body condition, and this
      prediction is also supported. Finally, parental effort should increase when
      partner condition decreases and vice versa; this prediction is partially
      supported. The Nash bargaining game may provide promising avenues by which to
      determine the precise settlement of reproductive skew and effort between
      coalition partners in the future.

PMID- 17206587
TI  - Maternal modulation of natal dispersal in a passerine bird: an adaptive strategy
      to cope with parasitism?
AB  - The decision of how far to disperse from the natal territory has profound and
      long-lasting consequences for young animals, yet the optimal dispersal behavior
      often depends on environmental factors that are difficult or impossible to assess
      by inexperienced juveniles. Natural selection thus favors mechanisms that allow
      the adaptive and flexible adjustment of the offspring's dispersal behavior by
      their parents via either paternal or maternal effects. Here we show that
      different dispersal strategies maximize the reproductive success of young great
      tits (Parus major) originating from a parasite-infested or a parasite-free nest
      and demonstrate that differential transfer of maternal yolk androgens in response
      to parasitism can result in a modification of the offspring's dispersal behavior
      that appears adaptive. It demonstrates that prenatal maternal effects are an
      important yet so far neglected determinant of natal dispersal and highlights the
      potential importance of maternal effects in mediating coevolutionary processes in
      host-parasite systems.

PMID- 17206588
TI  - Nest predation and the evolution of conspecific brood parasitism: from risk
      spreading to risk assessment.
AB  - Conspecific brood parasitism (CBP) is a taxonomically widespread reproductive
      tactic. One of the earliest hypotheses put forward to explain the evolution of
      CBP was "risk spreading"; that is, by laying eggs in more than one nest,
      parasites may increase the likelihood that at least one offspring will survive to
      independence. However, the risk spreading hypothesis, based on the assumptions of
      random nest predation and random selection of target nests by parasites, was
      theoretically refuted soon after its appearance. New results from the common
      goldeneye (Bucephala clangula) have revealed that nests are not predated at
      random and that parasites preferentially lay in safe nests. By taking into
      account these findings and by modifying accordingly the basic assumptions of the
      earlier model that refuted the risk spreading hypothesis, we built a model to
      address the role of nest predation in the evolution of CBP. Model simulations
      revealed that the selective advantage of parasitic laying, related to nest
      predation, is much higher than previously thought. Furthermore, the invasion
      probability of parasitic tactic when initially rare was reasonably high within
      our model framework. We show that the use of risk assessing, instead of random
      risk spreading, makes parasitic laying evolutionarily advantageous.

PMID- 17206589
TI  - The evolutionary and developmental basis of parallel reduction in mammalian
      zeugopod elements.
AB  - Understanding the mechanisms by which parallel evolution occurs has the potential
      to clarify the complex relationship between evolution and development. In this
      study, we examine the role of development in the repeated reduction of zeugopod
      elements during mammalian evolution, a functionally important phenomenon enabling
      locomotor specialization. By completing a morphometric study (incorporating both
      analyses of variation and phylogenetics) of mammalian limbs, we are able to
      demonstrate an evolutionary trend toward width reduction in posterior zeugopod
      elements of the forelimbs and hindlimbs, the ulna and fibula, respectively. We
      also examine the developmental basis of limb reduction in three test cases, the
      bat Carollia perspicillata ulna and fibula and the mouse Mus musculus fibula. The
      most common pattern of reduction, that of reduced element width, was achieved via
      the same developmental process in both bat and mouse limbs (i.e., by a slower
      growth rate relative to other skeletal elements), suggesting that the parallel
      reduction of the posterior zeugopod element within mammals could have occurred
      primarily by the repeated evolution of the same developmental mechanism. However,
      our findings also suggest that the developmental mechanisms behind the parallel
      evolution of other, more taxon-specific characteristics of limb reduction (i.e.,
      element fusion) are not conserved.

PMID- 17206590
TI  - Optimizing time and resource allocation trade-offs for investment into
      morphological and behavioral defense.
AB  - Prey organisms are confronted with time and resource allocation trade-offs. Time
      allocation trade-offs partition time, for example, between foraging effort to
      acquire resources and behavioral defense. Resource allocation trade-offs
      partition the acquired resources between multiple traits, such as growth or
      morphological defense. We develop a mathematical model for prey organisms that
      comprise time and resource allocation trade-offs for multiple defense traits.
      Fitness is determined by growth and survival during ontogeny. We determine
      optimal defense strategies for environments that differ in their resource
      abundance, predation risk, and defense effectiveness. We compare the results with
      results of simplified models where single defense traits are optimized. Our
      results indicate that selection acts in favor of integrated traits. The selective
      advantage of expressing multiple defense traits is most pronounced at
      intermediate environmental conditions. Optimizing single traits generally leads
      to a more pronounced response of the defense traits, which implies that studying
      single traits leads to an overestimation of their response to predation.
      Behavioral defense and morphological defense compensate for and augment each
      other depending on predator densities and the effectiveness of the defense
      mechanisms. In the presence of time constraints, the model shows peak investment
      into morphological and behavioral defense at intermediate resource levels.

PMID- 17206591
TI  - Winning by a neck: tall giraffes avoid competing with shorter browsers.
AB  - With their vertically elongated body form, giraffes generally feed above the
      level of other browsers within the savanna browsing guild, despite having access
      to foliage at lower levels. They ingest more leaf mass per bite when foraging
      high in the tree, perhaps because smaller, more selective browsers deplete shoots
      at lower levels or because trees differentially allocate resources to promote
      shoot growth in the upper canopy. We erected exclosures around individual Acacia
      nigrescens trees in the greater Kruger ecosystem, South Africa. After a complete
      growing season, we found no differences in leaf biomass per shoot across height
      zones in excluded trees but significant differences in control trees. We conclude
      that giraffes preferentially browse at high levels in the canopy to avoid
      competition with smaller browsers. Our findings are analogous with those from
      studies of grazing guilds and demonstrate that resource partitioning can be
      driven by competition when smaller foragers displace larger foragers from shared
      resources. This provides the first experimental support for the classic
      evolutionary hypothesis that vertical elongation of the giraffe body is an
      outcome of competition within the browsing ungulate guild.

PMID- 17206592
TI  - Variation in and correlation between intrinsic rate of increase and carrying
      capacity.
AB  - Intrinsic population growth rate and density dependence are fundamental
      components of population dynamics. Theory suggests that variation in and
      correlations between these parameters among patches within a population can
      influence overall population size, but data on the degree of variation and
      correlation are rare. Replicate populations of a specialist aphid (Chaetosiphon
      fragaefolii) were followed on 11 genotypes of host plant (Fragaria chiloensis) in
      the greenhouse. Population models fit to these census data provide estimates of
      intrinsic growth rate and carrying capacity for aphid populations on each plant
      genotype. Growth rate and carrying capacity varied substantially among plant
      genotypes, and these two parameters were not significantly correlated. These
      results support the existence of spatial variation in population dynamic
      parameters; data on frequency distributions and correlations of these parameters
      in natural populations are needed for evaluation of the importance of variation
      in growth rate and density dependence for population dynamics in the field.

PMID- 17206593
TI  - The evolution of sexually selected traits and antagonistic androgen expression in
      actinopterygiian fishes.
AB  - Many sexually selected traits in male fishes are controlled by testosterone.
      Directional selection for male ornaments could theoretically increase male
      testosterone levels over evolutionary timescales, and when genetically
      correlated, female testosterone levels as well. Because of the negative fitness
      consequences of high testosterone, it is plausible that female choice for
      sexually selected traits in males results in decreased female reproductive
      fitness. I used comparative analysis to examine the association between male peak
      testosterone expression and sexually selected ornaments. I also tested for
      genetic correlation between male and female androgen levels. The presence of
      sexually selected traits in males was significantly correlated with increased
      peak androgen levels in males as well as females, and female testosterone levels
      were significantly correlated with male peak testosterone titers, although the
      slope was only marginally <1. This suggests that selection to decouple high male
      and female testosterone levels is either weak or otherwise ineffective.

PMID- 17206594
TI  - Estimating the predictive quality of dose-response after model selection.
AB  - Prediction of dose-response is important in dose selection in drug development.
      As the true dose-response shape is generally unknown, model selection is
      frequently used, and predictions based on the final selected model. Correctly
      assessing the quality of the predictions requires accounting for the
      uncertainties caused by the model selection process, which has been difficult.
      Recently, a new approach called data perturbation has emerged. It allows
      important predictive characteristics be computed while taking model selection
      into consideration. We study, through simulation, the performance of data
      perturbation in estimating standard error of parameter estimates and prediction
      errors. Data perturbation was found to give excellent prediction error estimates,
      although at times large Monte Carlo sizes were needed to obtain good standard
      error estimates. Overall, it is a useful tool to characterize uncertainties in
      dose-response predictions, with the potential of allowing more accurate dose
      selection in drug development. We also look at the influence of model selection
      on estimation bias. This leads to insights into candidate model choices that
      enable good dose-response prediction.

PMID- 17206595
TI  - Simulation of high- and low-resolution mass spectra for assessment of calibration
      methods.
AB  - Calibrating mixtures of residual gases in quadrupole mass spectrometry (QMS) can
      be difficult since low m/z ratios of molecular ions and their fragments result in
      overlap of signals especially in the lower mass regions. This causes problems in
      univariate calibration methods and encourages use of full spectral multivariate
      methods. Experimental assessment of regression methods has limitations since
      experimental sources of error can only be minimised and not entirely eliminated.
      A method of simulating full spectra at low and high resolution to accurate masses
      is described and these are then used for a calibration study of some popular
      linear regression methods [classical least squares regression (CLS), partial
      least squares (PLS), principal component regression (PCR)].

PMID- 17206596
TI  - Evidence for the receipt of DNA damage stimuli by PML nuclear domains.
AB  - Promyelocytic leukaemia nuclear domains (PML-NDs) comprise a shell of PML protein
      and many labile cargo proteins. The nature of their cargo, their juxtaposition to
      foci of damaged DNA following ionizing radiation (IR), and the altered DNA damage
      responses in PML null cells all implicate PML-NDs in the DNA damage response. In
      this work, the propensity of PML-NDs to increase in number and decrease in size
      following IR has been studied. Serial quantitative studies of endogenous PML-NDs
      prove that the PML-ND response to IR is not the result of the asymmetry in cell
      cycle distribution that can follow IR, but reflects more directly the process of
      DNA damage. The response is swift, sensitive (evident after 1 Gy), and
      potentially reversible in untransformed fibroblasts. In these cells and in HCT116
      colon cancer cells, failure to restore PML-ND number within 24 h correlates with
      later loss of growth potential--in fibroblasts, through prolonged cell cycle
      arrest and in HCT116 cells, through apoptosis. Failure to express an intact
      ATM/CHK2 DNA damage signalling pathway in either cell type leads to a delay in
      the PML-ND response to IR. Conversely, cell cycle progression following IR in
      cells that detect damaged DNA accelerates PML-ND reorganization. Collectively,
      these data show that the increase in PML-ND number seen after irradiation is, in
      part, triggered by the receipt of the DNA damage stimulus. The senescent cell
      state is also associated with chronic DNA damage and Hayflick-limited fibroblasts
      were found to express nuclei with elevated numbers of PML-NDs before IR that
      remained unresponsive to IR. Though the underlying reasons for damage-induced PML
      alteration remain obscure, it is noteworthy that significant numbers of PML-NDs
      juxtapose with ionizing radiation-induced foci after IR. The co-regulation of
      these structures may necessitate the stereotyped increases in PML-ND number
      following damage.

PMID- 17206597
TI  - Determination of selenosugars in crude human urine using high-performance liquid
      chromatography/atmospheric pressure chemical ionization tandem mass spectrometry.
AB  - The narrow gap between essentiality and toxicity of selenium requires detailed
      investigations on selenium metabolism in order to find suitable indicators for
      the selenium status in the human body. Current methods for quantitative selenium
      speciation in human urine are based on separation by high-performance liquid
      chromatography (HPLC) coupled online with elemental mass spectrometry (MS), and
      the potential of molecular MS detection techniques for the reliable
      identification and quantification of selenosugars in crude human urine has not
      been utilized. Now we report the development of an HPLC tandem mass spectrometric
      (MS/MS) method for the reliable determination in crude human urine of three
      significant selenium urinary metabolites, collectively termed selenosugars,
      namely methyl 2-acetamido-2-deoxy-1-seleno-beta-D-galactopyranoside (SeGalNAc),
      methyl 2-acetamido-2-deoxy-1-seleno-beta-D-glucopyranoside (SeGluNAc) and methyl
      2-amino-2-deoxy-1-seleno-beta-D-galactopyranoside (SeGalNH2). Reversed-phase
      HPLC, with and without cation-exchange guard columns, was applied for the
      separation of the selenosugars, and atmospheric pressure chemical ionization
      (APCI) and selected reaction monitoring (SRM) were used for selective and
      sensitive detection. The collision-induced dissociation behaviour of the
      selenosugars was studied in detail using APCI triple quadrupole MS/MS and
      electrospray ion trap MS. The developed method was applied to urine samples
      collected prior to and after selenium supplementation for the quantification of
      SeGalNAc using both external calibration and the method of standard additions.
      Additionally, SeGalNH2 was detected in urine samples after Se supplementation.
      Finally, neutral loss scanning was explored as a possible method for the
      detection of unknown methyl-selenosugars.

PMID- 17206598
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for
      metabolic flux analyses using isotope-labeled ethanol.
AB  - We describe a novel method for the determination of the concentration and
      labeling degree of ethanol originating from 1-13C-labeling experiments. This
      method is suitable for high-throughput metabolic flux analysis because of the
      possible parallel sample preparation and fast final analysis using matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI
      TOFMS). In a closed vial containing culture supernatant, ethanol is enzymatically
      oxidized to acetaldehyde. The acetaldehyde formed evaporates and is readily
      trapped in a second enclosed but open vial containing acidified 2,4
      dinitrophenylhydrazine (DNPH). The 2,4-acetaldehyde dinitrophenylhydrazone (Ac
      DNPH) that is formed is insoluble under these conditions. This leads to a
      constant conversion rate of the acetaldehyde produced from ethanol after 14 h
      minimum incubation time. MALDI-TOFMS was used to quantify the formed Ac-DNPH with
      [13C2]-ethanol as internal standard. The relative signal intensities of the
      unlabeled ethanol derivative as well as of [1-13C]-ethanol were linearly related
      to the ethanol concentration within a range of 1 to 50 mM with a limit of
      detection of 0.6 mM, a range which is sufficient for flux analysis in microtiter
      plate fermentation experiments. The method allows the estimation of the [1-13C]
      ethanol originating from 1-13C-labeling experiments of Saccharomyces cerevisiae
      strains. In experiments where the expected flux range was exceeded, unlabeled
      ethanol was determined with a linear range from 30 to 500 mM. Ethanol
      quantification using this method was compared with enzymatic analysis and
      exhibited differences of less than 3.3% on average. Comparison of flux
      partitioning ratios between glycolysis and the pentose-phosphate pathway (PPP)
      based on MALDI-TOFMS and gas chromatography (GC)/MS methods showed good
      agreement, with differences for ethanol and alanine labeling of only 4.3%.

PMID- 17206599
TI  - Comprehensive analysis of proteins of pH fractionated samples using monolithic
      LC/MS/MS, intact MW measurement and MALDI-QIT-TOF MS.
AB  - A comprehensive platform that integrates information from the protein and peptide
      levels by combining various MS techniques has been employed for the analysis of
      proteins in fully malignant human breast cancer cells. The cell lysates were
      subjected to chromatofocusing fractionation, followed by tryptic digestion of pH
      fractions for on-line monolithic RP-HPLC interfaced with linear ion trap MS
      analysis for rapid protein identification. This unique approach of direct
      analysis of pH fractions resulted in the identification of large numbers of
      proteins from several selected pH fractions, in which approximately 1.5 microg of
      each of the pH fraction digests was consumed for an analysis time of ca 50 min.
      In order to combine valuable information retained at the protein level with the
      protein identifications obtained from the peptide level information, the same pH
      fraction was analyzed using nonporous (NPS)-RP-HPLC/ESI-TOF MS to obtain intact
      protein MW measurements. In order to further validate the protein identification
      procedures from the fraction digest analysis, NPS-RP-HPLC separation was
      performed for off-line protein collection to closely examine each protein using
      MALDI-TOF MS and MALDI-quadrupole ion trap (QIT)-TOF MS, and excellent agreement
      of protein identifications was consistently observed. It was also observed that
      the comparison to intact MW and other MS information was particularly useful for
      analyzing proteins whose identifications were suggested by one sequenced peptide
      from fraction digest analysis.

PMID- 17206600
TI  - Analysis of matched case-control data with multiple ordered disease states:
      possible choices and comparisons.
AB  - In an individually matched case-control study, effects of potential risk factors
      are ascertained through conditional logistic regression (CLR). Extension of CLR
      to situations with multiple disease or reference categories has been made through
      polychotomous CLR and is shown to be more efficient than carrying out separate
      CLRs for each subgroup. In this paper, we consider matched case-control studies
      where there is one control group, but there are multiple disease states with a
      natural ordering among themselves. This scenario can be observed when the cases
      can be further classified in terms of the seriousness or progression of the
      disease, for example, according to different stages of cancer. We explore several
      popular models for ordered categorical data in this context. We first adopt a
      cumulative logit or equivalently, a proportional-odds model to account for the
      ordinal nature of the data. The important distinction of this model from a
      stratified dichotomous and polychotomous logistic regression model is that the
      stratum-specific nuisance parameters cannot be eliminated in this model via the
      conditional-likelihood approach. We discuss a Mantel-Haenszel approach for
      analysing such data. We point out possible difficulties with standard likelihood
      based approaches with the cumulative logit model when applied to case-control
      data. We then consider an alternative conditional adjacent-category logit model.
      We illustrate the methods by analysing data from a matched case-control study on
      low birthweight in newborns where infants are classified according to low and
      very low birthweight and a child with normal birthweight serves as a control. A
      simulation study compares the different ordinal methods with methods ignoring sub
      classification of the ordered disease states.

PMID- 17206601
TI  - On modelling response propensity for dwelling unit (DU) level non-response
      adjustment in the Medical Expenditure Panel Survey (MEPS).
AB  - Non-response is a common problem in household sample surveys. The Medical
      Expenditure Panel Survey (MEPS), sponsored by the Agency for Healthcare Research
      and Quality (AHRQ), is a complex national probability sample survey. The survey
      is designed to produce annual national and regional estimates of health-care use,
      expenditures, sources of payment, and insurance coverage for the U.S. civilian
      non-institutionalized population. The MEPS sample is a sub-sample of respondents
      to the prior year's National Health Interview Survey (NHIS) conducted by the
      National Center for Health Statistics (NCHS). The MEPS, like most sample surveys,
      experiences unit, or total, non-response despite intensive efforts to maximize
      response rates. This paper summarizes research on comparing alternative
      approaches for modelling response propensity to compensate for dwelling unit
      (DU), i.e. household level non-response in the MEPS.Non-response in sample
      surveys is usually compensated for by some form of weighting adjustment to reduce
      the bias in survey estimates. To compensate for potential bias in survey
      estimates in the MEPS, two separate non-response adjustments are carried out. The
      first is an adjustment for DU level non-response at the round one interview to
      account for non-response among those households subsampled from NHIS for the
      MEPS. The second non-response adjustment is a person level adjustment to
      compensate for attrition across the five rounds of data collection. This paper
      deals only with the DU level non-response adjustment. Currently, the categorical
      search tree algorithm method, the chi-squared automatic interaction detector
      (CHAID), is used to model the response probability at the DU level and to create
      the non-response adjustment cells. In this study, we investigate an alternative
      approach, i.e. logistic regression to model the response probability. Main
      effects models and models with interaction terms are both evaluated. We further
      examine inclusion of the base weights as a covariate in the logistic models. We
      compare variability of weights of the two alternative response propensity
      approaches as well as direct use of propensity scores. The logistic regression
      approaches produce results similar to CHAID; however, using propensity scores
      from logistic models with interaction terms to form five classification groups
      for weight adjustment appears to perform best in terms of limiting variability
      and bias. Published in 2007 by John Wiley & Sons, Ltd.

PMID- 17206602
TI  - beta-Secretase expression in normal and functionally deprived rat olfactory
      bulbs: inverse correlation with oxidative metabolic activity.
AB  - Cerebral hypometabolism, mitochondrial dysfunction, and beta-amyloid peptide
      (Abeta) accumulation are well-characterized manifestations of Alzheimer's disease
      (AD). beta-Secretase (BACE) is a prerequisite for amyloidogenesis, and it is up
      regulated in sporadic AD. To explore a potential in vivo mechanism by which Abeta
      production is modulated by neuronal activity and/or oxidative metabolism, we
      compared BACE expression with cytochrome c oxidase (CO) or succinic dehydrogenase
      (SDH) activity in normal and functionally deprived adult rat olfactory bulb. In
      normal bulb, BACE was expressed predominantly in the glomerular layer, but
      labeling intensity within individual glomeruli varied substantially. A strong
      negative correlation existed between BACE labeling intensity and CO or SDH
      activity among individual glomeruli. Unilateral naris occlusion resulted in
      elevated glomerular BACE labeling in the deprived bulbs relative to the
      nondeprived counterparts, which was correlated with decreased CO activity in the
      same anatomic location. Enhanced BACE labeling was confirmed by measurements of
      elevated protein levels, enzymatic activity, and beta-site cleavage products of
      amyloid precursor protein in bulb extracts. Our findings reveal a negative
      regulation of BACE expression by physiological neuronal activity and an intrinsic
      inverse correlation between BACE expression and oxidative metabolism at the first
      synapse on the olfactory pathway. The results point to a biological role of BACE
      in synapse function and plasticity as well as a potential mechanism whereby
      reduced neuronal activity or metabolism could lead to amyloid overproduction in
      synaptic terminals.

PMID- 17206603
TI  - Cortical and thalamic connections of the representations of the teeth and tongue
      in somatosensory cortex of new world monkeys.
AB  - Connections of representations of the teeth and tongue in primary somatosensory
      cortex (area 3b) and adjoining cortex were revealed in owl, squirrel, and
      marmoset monkeys with injections of fluorescent tracers. Injection sites were
      identified by microelectrode recordings from neurons responsive to touch on the
      teeth or tongue. Patterns of cortical label were related to myeloarchitecture in
      sections cut parallel to the surface of flattened cortex, and to coronal sections
      of the thalamus processed for cytochrome oxidase (CO). Cortical sections revealed
      a caudorostral series of myelin dense ovals (O1-O4) in area 3b that represent the
      periodontal receptors of the contralateral teeth, the contralateral tongue, the
      ipsilateral teeth, and the ipsilateral tongue. The ventroposterior medial
      subnucleus, VPM, and the ventroposterior medial parvicellular nucleus for taste,
      VPMpc, were identified in the thalamic sections. Injections placed in the O1 oval
      representing teeth labeled neurons in VPM, while injections in O2 representing
      the tongue labeled neurons in both VPMpc and VPM. These injections also labeled
      adjacent part of areas 3a and 1, and locations in the lateral sulcus and frontal
      lobe. Callosally, connections of the ovals were most dense with corresponding
      ovals. Injections in the area 1 representation of the tongue labeled neurons in
      VPMpc and VPM, and ipsilateral area 3b ovals, area 3a, opercular cortex, and
      cortex in the lateral sulcus. Contralaterally, labeled neurons were mostly in
      area 1. The results implicate portions of areas 3b, 3a, and 1 in the processing
      of tactile information from the teeth and tongue, and possibly taste information
      from the tongue.

PMID- 17206605
TI  - Synthesis of new 4-heteroaryl-2-phenylquinolines and their pharmacological
      activity as NK-2/NK-3 receptor ligands.
AB  - Substituted 4-heteroaryl-2-phenylquinolines were synthesized and tested on NK-2
      and NK-3 receptors in order to get a better insight in the structure-activity
      relationship. On the whole, these molecules, which can be regarded as bioisosters
      of the NK-3 antagonist SB 218795, displayed a lower activity than the template.
      Ring electronic distribution and H-bond donor and acceptor positions played some
      role in selectivity, 2-imidazolyl substituted 2a showing affinity mainly towards
      NK-3 while 3-pyrazolyl substituted 4 displayed a preferential interaction with NK
      2 receptor. Structural characterization of the synthesized compounds was achieved
      by NMR and mass techniques. Bidimensional 1H-NOESY experiments were a helpful
      tool for the assignment of the isomeric structures of compounds 9 and llb-c.

PMID- 17206606
TI  - Synthesis, DNA binding and antiviral activity of new uracil, xanthine, and
      pteridine derivatives.
AB  - Some new 6-amino-1,3-dimethyl-5-(substituted methylidene)aminouracils were
      synthesized. Most of them were cyclized with triethyl orthoformate as a one
      carbon source to afford 1,3-dime-thyl-6-substituted pteridine derivatives.
      Certain uracils gave xanthine instead of the expected pteridine derivatives upon
      using another one-carbon source such as triethyl orthoacetate or triethyl
      orthobenzoate. The nucleic acid binding assay revealed that some new compounds
      showed high affinity, chelation, and fragmentation of nucleic acids whether DNA
      or RNA contrary to acyclovir that has affinity to DNA only. The antiviral
      activity of these novel compounds showed that compounds 2e and 2f reduced the
      cytopathogencity of Peste des petits ruminant virus (PPRV) on Vero cell culture
      by 60 and 50%, respectively.

PMID- 17206607
TI  - The organization of frontoparietal cortex in the tree shrew (Tupaia belangeri):
      II. Connectional evidence for a frontal-posterior parietal network.
AB  - Tree shrews are small squirrel-like mammals that are the closest living relative
      to primates available for detailed neurobiological study. In a recent study
      (Remple et al. [2006] J. Comp. Neurol. 497:133-154), we provided anatomical and
      electrophysiological evidence that the frontoparietal cortex of tree shrews has
      two motor fields (M1 and M2) and five somatosensory fields (3a, 3b, S2,
      somatosensory caudal area [SC], and parietal ventral area [PV]). In the present
      study, we injected anatomical tracers into M1, M2, 3a, 3b, SC, and posterior
      parietal cortex to establish the ipsilateral cortical connections of these areas.
      The results provide evidence for a number of new cortical areas including medial
      motor and somatosensory areas (MMA and MSA), three posterior parietal areas (PPd,
      PPv, and PPc), and an area ventral to temporal inferior cortex (TIV). Ml receives
      topographic projections from M2, MMA, 3a, and PPv, and nontopographic connections
      from the temporal anterior and dorsal areas (TA and TD), PPc, TIV, and MSA. The
      connections of M2 are similar to those of M1, except that M2 receives denser
      projections from TIV, PPc, and dorsal frontal cortex and sparser input from M1.
      Areas 3a, 3b, and SC receive dense topographic projections from each other, S2,
      and PV and sparser connections from PPd and PPv. Area 3a receives additional
      input from posterior parietal and temporal regions and from M1 and MMA. Overall,
      the frontoparietal connections of tree shrew cortex are most similar to those of
      prosimian primates and quite different from those of more distant relatives such
      as rats.

PMID- 17206608
TI  - Aminocarbonyloxymethyl ester prodrugs of flufenamic acid and diclofenac:
      suppressing the rearrangement pathway in aqueous media.
AB  - Aminocarbonyloxymethyl ester prodrugs are known to undergo rearrangement in
      aqueous solutions to form the corresponding N-acylamine side product via an O-->N
      intramolecular acyl transfer from the carbamate conjugate base. Novel
      aminocarbonyloxymethyl esters of diclofenac and flufenamic acid containing amino
      acid amide carriers were synthesized and evaluated as potential prodrugs
      displaying less ability to undergo rearrangement. These compounds were prepared
      in reasonable yield by a four-step synthetic method that uses the appropriate N
      Boc-protected amino acid N-hydroxysuccinimide ester and secondary amine and
      chloromethyl chloroformate as key reactants. Their reactivity in pH 7.4 buffer
      and 80% human plasma at 37 degrees C was assessed by RP-HPLC. The
      aminocarbonyloxymethyl esters containing a secondary carbamate group derived from
      amino acids such as glycine or phenylalanine were hydrolyzed quantitatively to
      the parent drug both in non-enzymatic and enzymatic conditions, with no
      rearrangement product being detected. The oral bioavailability in rats was
      determined for selected diclofenac derivatives. These derivatives displayed a
      bioavailability of 25 to 68% relative to that of diclofenac, probably due to
      their poor aqueous solubility and lipophilicity. These results suggest that
      further optimization of aminocarbonyloxymethyl esters as potential prodrugs for
      non-steroidal anti-inflammatory drugs require the use of amino acid carriers with
      ionizable groups to improve aqueous solubility.

PMID- 17206609
TI  - Synthesis and pharmacological evaluation of some 3-(4-methylphenyl)-2-substituted
      amino-3H-quinazolin-4-ones as analgesic and anti-inflammatory agents.
AB  - A variety of 3-(4-methyl phenyl)-2-substituted amino-3H-quinazolin-4-ones were
      synthesized by reacting the amino group of 2-hydrazino-3-(4-methyl phenyl)-3H
      quinazolin-4-one with a variety of aldehydes and ketones. The starting material 2
      hydrazino-3-(4-methyl phenyl)-3H-quinazolin-4-one was synthesized from 4-methyl
      aniline. The title compounds were investigated for analgesic, anti-inflammatory,
      and ulcerogenic index activities. While the test compounds exhibited significant
      activity, compounds Al, A2, and A3 showed more potent analgesic activity and the
      compound A3 showed more potent anti-inflammatory activity when compared to the
      reference standard diclofenac sodium. Interestingly, the test compounds showed
      only mild ulcerogenic potential when compared to aspirin.

PMID- 17206610
TI  - Synthesis and antibacterial activity of new 7-piperazinyl-quinolones containing a
      functionalized 2-(furan-3-yl)ethyl moiety.
AB  - A number of 7-piperazinylquinolones carrying a functionalized 2-(furan-3-yl)ethyl
      moiety attached to the piperazine ring have been synthesized and evaluated as
      antibacterial agents against a panel of Gram-positive and Gram-negative bacteria.
      Most of the synthesized compounds exhibited significant antibacterial activity,
      and this activity can be modulated through the nature of the functionality on
      ethyl spacer attached to piperazine ring and the type of side chain present at
      the N-1 position of quinolone ring.

PMID- 17206611
TI  - Breaches of the pial basement membrane and disappearance of the glia limitans
      during development underlie the cortical lamination defect in the mouse model of
      muscle-eye-brain disease.
AB  - Neuronal overmigration is the underlying cellular mechanism of cerebral cortical
      malformations in syndromes of congenital muscular dystrophies caused by defects
      in O-mannosyl glycosylation. Overmigration involves multiple developmental
      abnormalities in the brain surface basement membrane, Cajal-Retzius cells, and
      radial glia. We tested the hypothesis that breaches in basement membrane and the
      underlying glia limitans are the key initial events of the cellular
      pathomechanisms by carrying out a detailed developmental study with a mouse model
      of muscle-eye-brain disease, mice deficient in O-mannose beta31,2-N
      acetylglucosaminyltransferase 1 (POMGnT1). The pial basement membrane was normal
      in the knockout mouse at E11.5. It was breached during rapid cerebral cortical
      expansion at E13.5. Radial glial endfeet, which comprise glia limitans, grew out
      of the neural boundary. Neurons moved out of the neural boundary through these
      breaches. The overgrown radial glia and emigrated neurons disrupted the overlying
      pia mater. The overmigrated neurons did not participate in cortical plate (CP)
      development; rather they formed a diffuse cell zone (DCZ) outside the original
      cortical boundary. Together, the DCZ and the CP formed the knockout cerebral
      cortex, with disappearance of the basement membrane and the glia limitans. These
      results suggest that disappearance of the basement membrane and the glia limitans
      at the cerebral cortical surface during development underlies cortical lamination
      defects in congenital muscular dystrophies and a cellular mechanism of cortical
      malformation distinct from that of the reeler mouse, double cortex syndrome, and
      periventricular heterotopia.

PMID- 17206612
TI  - Effects of impromidine- and arpromidine-derived guanidines on recombinant human
      and guinea pig histamine H1 and H2 receptors.
AB  - Imidazolylpropylguanidines derived from impromidine and arpromidine are more
      potent and efficacious agonists at the guinea pig histamine H2 receptor (gpH2R)
      than at the human H2R (hH2R) in the GTPase assay. Additionally, such guanidines
      are histamine H1 receptor (H1R) antagonists with preference for the human
      relative to the guinea pig receptor. The purpose of this study was to examine
      structure-activity relationships of guanidines at human and guinea pig H1R and
      H2R species isoforms expressed in Sf9 insect cells. Three impromidine analogues
      and six arpromidine analogues exhibited agonistic activity at H2R and
      antagonistic activity at H1R as assessed in the steady-state GTPase assay.
      Species selectivity of derivatives was similar as compared with the parent
      compounds. None of the structural modifications examined (different aromatic ring
      systems and different ring substituents) was superior in terms of H2R potency and
      efficacy relative to impromidine and arpromidine, respectively. These data point
      to substantial structural constraints at the agonist binding site of H2R.
      Guanidines exhibited distinct structure-activity relationships for H1R antagonism
      in a radioligand competition binding assay and the GTPase assay and for H1R
      inverse agonism. Our data indicate that it is difficult to obtain guanidine-type
      agonists with high potency and high efficacy for hH2R, but those compounds may be
      useful tools for exploring the antagonist binding site and constitutive activity
      of H1R.

PMID- 17206613
TI  - Enzymes that synthesize the IB4 epitope are not sufficient to impart IB4 binding
      in dorsal root ganglia of rat.
AB  - The isolectin B4 (IB4) stains a subset of small and medium-sized dorsal root
      ganglion (DRG) neurons by binding to terminal alpha-galactose on glycoproteins
      and glycolipids. The enzymes alpha(1,3)galactosyltransferase (1,3GT) and
      isoglobotriaosylceramide synthase (iGb3S) synthesize the galactose-alpha(1,3)
      galactose group, which is the most common carbohydrate containing terminal alpha
      galactose. 1,3GT preferentially glycosylates proteins whereas iGb3S glycosylates
      lipids. We generated antibodies against rat 1,3GT and iGb3S that were used for
      immunohistochemical staining of DRG cells. Virtually all neurons that bound IB4
      expressed both enzymes, suggesting that IB4 binds to both glycoproteins and
      glycolipids in IB4-positive neurons. 1,3GT immunoreactivity was observed in small
      and medium-sized neurons and satellite cells. iGb3S immunoreactivity was observed
      in neurons of varying sizes. Many neurons that expressed these enzymes did not
      bind IB4. Additionally, the majority of neurons that expressed substance P
      expressed both enzymes but did not bind IB4. Ultrastructual studies revealed that
      1,3GT was predominantly associated with the Golgi apparatus, whereas iGb3S was
      found near the Golgi apparatus and in large, clear vesicles throughout the soma.
      These data suggest that, although expression of 1,3GT and/or iGb3S appears to be
      necessary for IB4 binding, expression of these enzymes is not sufficient to
      impart IB4 binding.

PMID- 17206614
TI  - Identification of aromatase-positive radial glial cells as progenitor cells in
      the ventricular layer of the forebrain in zebrafish.
AB  - Compared with other vertebrates, the brain of adult teleost fish exhibits two
      unique features: it exhibits unusually high neurogenic activity and strongly
      expresses aromatase, a key enzyme that converts aromatizable androgens into
      estrogens. Until now, these two features, high neurogenic and aromatase
      activities, have never been related to each other. Recently, it was shown that
      aromatase is expressed in radial glial cells of the forebrain and not in neurons.
      Here, we further document that Aromatase B is never detected in cells expressing
      the markers of postmitotic neurons, Hu and acetylated tubulin. By using a
      combination of bromodeoxyuridine (BrdU) treatment and immunohistochemical
      techniques, we demonstrate for the first time to our knowledge that aromatase
      positive radial cells actively divide to generate newborn cells in many forebrain
      regions. Such newborn cells can further divide, as shown by BrdU-proliferating
      cell nuclear antigen double staining. We also demonstrate that, over time,
      newborn cells move away from the ventricles, most likely by migrating along the
      radial processes. Finally, by using antisera to Hu and acetylated tubulin, we
      further document that some of the newborn cells derived from radial glia
      differentiate into neurons. These data provide new evidence for the mechanism of
      neurogenesis in the brain of adult fish. In addition, given that estrogens are
      well-known neurotrophic and neuroprotective factors affecting proliferation,
      apoptosis, migration, and differentiation, the expression of aromatase in the
      neural stem cells of the adult strongly demonstrates that the fish brain is an
      outstanding model for studying the effects of estrogens on adult neurogenesis and
      brain repair.

PMID- 17206615
TI  - Dynamic expression of the basic helix-loop-helix transcription factor neuroD in
      the rod and cone photoreceptor lineages in the retina of the embryonic and larval
      zebrafish.
AB  - NeuroD is a basic helix-loop-helix (bHLH) transcription factor critical for
      determining neuronal cell fate and regulating withdrawal from the cell cycle. We
      showed previously that, in goldfish, neuroD is expressed in the rod photoreceptor
      lineage, and we inferred that neuroD is also expressed in a subset of amacrine
      cells and nascent cone photoreceptors. Here we extended that study by examining
      the temporal and spatial expression pattern of neuroD in the embryonic and larval
      zebrafish and by identifying the cell types that express this gene. NeuroD
      expression in the developing zebrafish retina is dynamic, spanning early
      retinogenesis and the maturation of cone photoreceptors. In early retinogenesis
      neuroD expression expands from a small patch in the ventronasal retina, through
      the remaining retinal neuroepithelium. As retinogenesis progresses, neuroD
      expression becomes restricted to amacrine cells, immature cones, and cells of rod
      and cone lineages. This expression achieves an adult pattern by 96 hours
      postfertilization (hpf), whereupon the temporal pattern of neuroD expression in
      central retina is spatially recapitulated at the germinative margin. The cellular
      pattern of expression suggests that neuroD regulates aspects of rod and cone
      genesis, but through separate cellular lineages. Furthermore, neuroD is
      coexpressed with the cone-rod-homeobox transcription factor (Crx) in putative
      cone progenitors and nascent cone photoreceptors, suggesting that, in the
      zebrafish retina, as in other vertebrate retinas, similar genetic cascades
      regulate photoreceptor genesis and maturation.

PMID- 17206616
TI  - Relationship of complex spike synchrony bands and climbing fiber projection
      determined by reference to aldolase C compartments in crus IIa of the rat
      cerebellar cortex.
AB  - Synchronous complex spike (CS) activity occurs most often among cerebellar
      Purkinje cells located in a narrow longitudinal (parasagittal) strip of cortex
      (synchrony band). The relationship of the anatomical organization of the
      olivocerebellar projection to these synchrony bands has not been investigated in
      detail. Thus, we studied this relationship by using the aldolase C (zebrin II)
      expression pattern, another landmark for the cerebellar longitudinal
      organization, as a reference frame in rat crus IIa. Crus IIa consists of 10
      aldolase C-positive and -negative longitudinal compartments. Aldolase C labeling
      after multiple-electrode recording of CSs indicated that in lateral crus IIa
      (compartments 5+ to 7+) synchrony bands were generally constrained to single
      compartments. In contrast, in medial crus IIa (compartments 4a- to 5a-) the
      synchrony within and across the compartments was much higher than in lateral crus
      IIa, resulting in wide synchrony bands covering multiple compartments. Retrograde
      labeling of olivary neurons by injections of biotinylated dextran amine into
      aldolase C compartments in crus IIa showed that compartments in medial crus IIa
      were all innervated by the caudal part of the medial accessory olive. On the
      other hand, each aldolase C compartment in the lateral crus IIa was innervated by
      a region in a different subnucleus in the rostral inferior olive. These regions
      in different subnuclei were located close to each other. These results suggest
      that CS synchrony bands reflect the olivocerebellar compartmental projection
      pattern and neuronal coupling within a particular olivary subnucleus, and that
      medial and lateral crus IIa may be functionally distinct.

PMID- 17206617
TI  - Dynamic patterns of neurotrophin 3 expression in the postnatal mouse inner ear.
AB  - Recent studies indicate that neurotrophin 3 (NT3) may be important for the
      maintenance and function of the adult inner ear, but the pattern of postnatal NT3
      expression in this organ has not been characterized. We used a reporter mouse in
      which cells expressing NT3 also express beta-galactosidase, allowing for their
      histochemical visualization, to determine the pattern of NT3 expression in
      cochlear and vestibular organs. We analyzed animals from birth (P0) to adult
      (P135). At P0, NT3 was strongly expressed in supporting cells and hair cells of
      all vestibular and cochlear sense organs, Reissner's membrane, saccular membrane,
      and the dark cells adjacent to canal organs. With increasing age, staining
      disappeared in most cell types but remained relatively high in inner hair cells
      (IHCs) and to a lesser extent in IHC supporting cells. In the cochlea, by P0
      there is a longitudinal gradient (apex > base) that persists into adulthood. In
      vestibular maculae, staining gradients are: striolar > extrastriolar regions and
      supporting cells > hair cells. By P135, cochlear staining is restricted to IHCs
      and their supporting cells, with stronger expression in the apex than the base.
      By the same age, in the vestibular organs, NT3 expression is weak and restricted
      to saccular and utricular supporting cells. These results suggest that NT3 might
      play a long-term role in the maintenance and functioning of the adult auditory
      and vestibular systems and that supporting cells are the main source of this
      factor in the adult.

PMID- 17206618
TI  - Embryonic differentiation of serotonin-containing neurons in the enteric nervous
      system of the locust (Locusta migratoria).
AB  - The enteric nervous system (ENS) of the locust consists of four ganglia (frontal
      and hypocerebral ganglion, and the paired ingluvial ganglia) located on the
      foregut, and nerve plexus innervating fore- and midgut. One of the major
      neurotransmitters of the ENS, serotonin, is known to play a vital role in gut
      motility and feeding. We followed the anatomy of the serotonergic system
      throughout embryonic development. Serotonergic neurons are generated in the
      anterior neurogenic zones of the foregut and migrate rostrally along the
      developing recurrent nerve to contribute to the frontal ganglion. They grow
      descending neurites, which arborize in all enteric ganglia and both nerve plexus.
      On the midgut, the neurites closely follow the leading migrating midgut neurons.
      The onset of serotonin synthesis occurs around halfway through development-the
      time of the beginning of midgut closure. Cells developing to serotonergic
      phenotype express the serotonin uptake transporter (SERT) significantly earlier,
      beginning at 40% of development. The neurons begin SERT expression during
      migration along the recurrent nerve, indicating that they are committed to a
      serotonergic phenotype before reaching their final destination. After completion
      of the layout of the enteric ganglia (at 60%) a maturational phase follows,
      during which serotonin-immunoreactive cell bodies increase in size and the fine
      arborizations in the nerve plexus develop varicosities, putative sites of
      serotonin release (at 80%). This study provides the initial step for future
      investigation of potential morphoregulatory functions of serotonin during ENS
      development.

PMID- 17206619
TI  - Upregulation of aggrecan, link protein 1, and hyaluronan synthases during
      formation of perineuronal nets in the rat cerebellum.
AB  - Extracellular matrix molecules accumulate around central nervous system neurons
      during postnatal development, forming so-called perineuronal nets (PNNs). PNNs
      play a role in restricting plasticity at the end of critical periods. In the
      adult rat cerebellum, PNNs are found around large, deep cerebellar nuclei (DCN)
      neurons and Golgi neurons and are composed of chondroitin sulfate proteoglycans
      (CSPGs), tenascin-R (TN-R), hyaluronan (HA), and link proteins, such as cartilage
      link protein 1 (Crtll). Granule cells and Purkinje cells are surrounded by a
      partially organized matrix. Both glial cells and neurons surrounded by PNNs are
      the site of synthesis of some CSPGs and of TN-R, but only neurons produce HA
      synthetic enzymes (HASs), thus HA, and link proteins, which are scaffolding
      molecules for an organized matrix. To elucidate the mechanisms of formation of
      PNNs, we analyzed by immunohistochemistry and in situ hybridization which PNN
      components are upregulated during PNN formation in rat cerebellar postnatal
      development and what cell types express them. We observed that Wisteria
      floribunda agglutinin-binding PNNs develop around DCN neurons from postnatal day
      (P)7 and around Golgi neurons from P14. At the same time as their PNNs start to
      form, these neurons upregulate aggrecan, Crtll, and HASs mRNAs. However, Crtll is
      the only PNN component to be expressed exclusively in neurons surrounded by PNNs.
      The other link protein that shows a perineuronal net pattern in the DCN, Bral2,
      is upregulated later during development. These data suggest that aggrecan, HA,
      and, particularly, Crtll might be crucial elements for the initial assembly of
      PNNs.

PMID- 17206620
TI  - Y-position cysteine substitution in type I collagen (alpha1(I) R888C/p.R1066C) is
      associated with osteogenesis imperfecta/Ehlers-Danlos syndrome phenotype.
AB  - The most common mutations in type I collagen causing types II-IV osteogenesis
      imperfecta (OI) result in substitution for glycine in a Gly-Xaa-Yaa triplet by
      another amino acid. We delineated a Y-position substitution in a small pedigree
      with a combined OI/Ehlers-Danlos Syndrome (EDS) phenotype, characterized by
      moderately decreased DEXA z-score (-1.3 to -2.6), long bone fractures, and large
      joint hyperextensibility. Affected individuals have an alpha1(I)R888C (p.R1066C)
      substitution in one COL1A1 allele. Polyacrylamide gel electrophoresis (PAGE) of
      [(3)H]-proline labeled steady-state collagen reveals slight overmodification of
      the alpha1(I) monomer band, much less than expected for a substitution of a
      neighboring glycine residue, and a faint alpha1(I) dimer. Dimers form in about
      10% of proband type I collagen. Dimer formation is inefficient compared to a
      possible 25%, probably because the SH-side chains have less proximity in this Y
      position than when substituting for a glycine. Theoretical stability
      calculations, differential scanning calorimetry (DSC) thermograms, and thermal
      denaturation curves showed only weak local destabilization from the Y-position
      substitution in one or two chains of a collagen helix, but greater
      destabilization is seen in collagen containing dimers. Y-position collagen dimers
      cause kinking of the helix, resulting in a register shift that is propagated the
      full length of the helix and causes resistance to procollagen processing by N
      proteinase. Collagen containing the Y-position substitution is incorporated into
      matrix deposited in culture, including immaturely and maturely cross-linked
      fractions. In vivo, proband dermal fibrils have decreased density and increased
      diameter compared to controls, with occasional aggregate formation. This report
      on Y-position substitutions in type I collagen extends the range of phenotypes
      caused by nonglycine substitutions and shows that, similar to X- and Y-position
      substitutions in types II and III collagen, the phenotypes resulting from
      nonglycine substitutions in type I collagen are distinct from those caused by
      glycine substitutions.

PMID- 17206621
TI  - Combined use of WEB2170 and HBO therapy can reduce ischemia and reperfusion
      injury to the skeletal muscle in a rabbit model.
AB  - Ischemia/reperfusion injury is regarded as the main cause of failure in
      revascularization of limbs and transfer of free flaps in the so called nonreflow
      phenomenon. This type of damage is caused by the production of free radicals,
      above all, of neutrophils that release great quantities of extracellular
      superoxide through the action of a membrane enzyme. In our study we used 40 white
      rabbits. Rabbit rectus femoris muscle is perfused by a single artery and vein and
      is therefore a valuable model for study of ischemia-induced reperfusion injury of
      skeletal muscle. The objective of this study was to individualize a valid method
      of protection for the muscle from damage by ischemia-induced reperfusion injury.
      We have tested the effectiveness of WEB2170, a PAF antagonist, of hyperbaric
      oxygen therapy one (HBO), and of combined employment of WEB2170 and HBO. The
      results show that both PAF and HBO play important protective roles against damage
      from ischemia/reperfusion injury, and that the combined employment of both
      therapies has a synergistic effect. We propose therefore a new therapeutic
      protocol for the prevention of damage resulting from ischemia/reperfusion injury
      with the simultaneous employment of this PAF and HBO.

PMID- 17206622
TI  - Dangers associated with endoscopic management of strictures in IBD.

PMID- 17206623
TI  - Computational study of the absorption spectra of green fluorescent protein
      mutants.
AB  - In this work, we present a theoretical study of the relationship between
      molecular structure and the red-shift in absorption spectra of S65G and S65T
      green fluorescent protein (GFP) mutants. To identify the effects of the protein
      environment, we combined results from molecular dynamics (MD) simulations and
      quantum mechanics/molecular mechanics calculations to obtain structural
      properties, and applied time-dependent density functional theory to calculate the
      excitation energies. By using results from the MD simulations, we were able to
      provide a systematic analysis of the structural details that may effect the red
      shift in the absorption spectra when taking into account temperature effects.
      Furthermore, a detailed study of hydrogen bonding during the MD simulations
      demonstrated differences between S65G and S65T, for example, regarding hydrogen
      bonding with Glu222. An analysis of the absorption spectra for different forms of
      the chromophore emphasized the dominance of the anionic forms in solution for the
      S65G and S65T GFP mutants.

PMID- 17206624
TI  - Interactions between peptides containing nucleobase amino acids and T7 phages
      displaying S. cerevisiae proteins.
AB  - The importance of high-throughput analyses of protein abundances and functions is
      interestingly increasing in genomic/proteomic studies. In such postgenome
      sequencing era, a protein-detecting chip, in which a large number of molecules
      specifically capturing target proteins (capturing agents) such as antibodies,
      recombinant proteins, and small molecules are arrayed onto solid, wet, or semi
      wet substrates, enables comprehensive analysis of proteomes by a single
      experiment. However, whole proteomes are generally complicated for comprehensive
      analyses so that alternative approaches to subproteome analysis categorized by
      protein functions and binding properties (focused proteome) would be effective.
      Approaching the goal of development of designed peptide chip for protein
      analysis, diversity increases in peptide structures and validation of target
      proteins are needed. We herein describe design and synthesis of nucleobase amino
      acid (NBA)-containing peptides, selection of nucleic acid-related proteins
      derived from S. cerevisiae, and detection of interactions between NBA-containing
      peptides and T7 phages displaying proteins by both enzyme-linked immunosorbent
      assays (ELISA) and label-free anomalous reflection of gold (AR) measurements.
      Twenty-eight phage clones were obtained by the phage-display method and
      sequenced. Ten of 28 clones were expected to be nucleic acid-related proteins
      including initiation factor, TYB protein, ribosomal proteins, elongation factor,
      ATP synthase subunit, GTP-binding protein, and ribonuclease. Other phage clones
      encoded several classes of enzymes such as reductase, oxidase, aldolase,
      metalloprotease, and hexokinase. Both ELISA and AR measurements suggested that
      the methodology of in vitro selection for recognition of the NBA-containing
      peptide presented in this study was successfully established. Such a combination
      of NBA and phage display technologies would be potential to efficiently confirm
      valuable target proteins binding specifically to capturing agents, to be arrayed
      onto solid surfaces to develop the designed peptide chip.

PMID- 17206625
TI  - Relationship between blood compatibility and water structure--comparative study
      between 2-methoxyethylacrylate- and 2-methoxyethylmethacrylate-based random
      copolymers.
AB  - We have proposed that the excellent blood compatibility of poly(2
      methoxyethylacrylate (MEA)) is caused by freezing bound water contained in it on
      the basis of results on platelet activation (Tanaka and Mochizuki, J Biomed Mater
      Res A 2004; 68:684-695). To clarify the applicability of this mechanism to other
      indexes for blood compatibility, the relationship between complement activation
      and water structure was investigated by using two copolymers, poly(MEA-2
      hydroxyethylmethacrylate (HEMA)) and poly(2-methoxyethylmethacrylate (MEMA)
      HEMA), where HEMA content was varied from 25 to 90 mol %. ESCA analysis revealed
      that the surface compositions of these copolymers (dry state) agreed with the
      compositions determined by (1)H NMR. However, analysis by water contact angle
      (wet state) showed that their surfaces were quite different. The contact angle of
      poly(MEMA-HEMA) depended on the monomer composition, whereas the angle of
      poly(MEA-HEMA) was close to that of polyHEMA regardless of the monomer
      composition. The effect of HEMA content in the copolymers on complement
      activation (production of C3a) was investigated in an in vitro test. The
      activation by poly(MEMA-HEMA) was enhanced according to the HEMA content, while
      the activation by poly(MEA-HEMA) with 0-40 mol % of HEMA was weak and did not
      depend on the HEMA content. These properties are discussed from the viewpoints of
      the water structure observed by DSC and the surface structure.

PMID- 17206626
TI  - Switch-peptides as folding precursors in self-assembling peptides and amyloid
      fibrillogenesis.
AB  - The study of conformational transitions of peptides has obtained considerable
      attention recently because of their importance as a molecular key event in a
      variety of degenerative diseases. However, the study of peptide self-assembly
      into beta-sheets and amyloid beta (Abeta) fibrils is strongly hampered by their
      difficult synthetic access and low solubility. We have recently developed a new
      concept termed switch-peptides that allows the controlled onset of polypeptide
      folding and misfolding at physiologic conditions. As a major feature, the folding
      process is initiated by chemically or enzyme triggered O,N-acyl migration in
      flexible and soluble folding precursors containing Ser- or Thr-derived switch (S)
      elements. The elaborated methodologies are exemplified for the in situ conversion
      of NPY- and Cyclosporine A-derived prodrugs, as well as for the onset and
      reversal of alpha and beta conformational transitions in Abeta peptides. In
      combining orthogonally addressable switch-elements, the consecutive switching on
      of S-elements gives new insights into the role of individual peptide segments
      (hot spots) in early processes of polypeptide self-assembly and fibrillogenesis.
      Finally, the well-known secondary structure disrupting effect of pseudoprolines
      (PsiPro) is explored for its use as a building block (S-element) in switch
      peptides. To this end, synthetic strategies are described, allowing for the
      preparation of PsiPro-containing folding precursors, exhibiting flexible random
      coil conformations devoid of fibril forming propensity. The onset of beta-sheet
      and fibril formation by restoring the native peptide chain in a single step
      classify PsiPro-units as the most powerful tool for inhibiting peptide self
      assembly, and complement the present methodologies of the switch-concept for the
      study of fibrillogenesis.

PMID- 17206627
TI  - Activity based fingerprinting of proteases using FRET peptides.
AB  - We have successfully developed a protease assay using fluorescence resonance
      energy transfer based peptide libraries, which allows not only general detection
      of enzymatic activities, but more importantly substrate fingerprinting of
      proteases from different classes. The method allows the generation of substrate
      fingerprints of a protease from both the nonprime and prime sites. Therefore, it
      is well suited for profiling of major metalloproteases such as thermolysin and
      MMPs. We envisage that this method will provide a useful tool in the emerging
      field of Catalomics for high-throughput studies of proteases.

PMID- 17206628
TI  - From the test tube to the cell: exploring the folding and aggregation of a beta
      clam protein.
AB  - A crucial challenge in present biomedical research is the elucidation of how
      fundamental processes like protein folding and aggregation occur in the complex
      environment of the cell. Many new physico-chemical factors like crowding and
      confinement must be considered, and immense technical hurdles must be overcome in
      order to explore these processes in vivo. Understanding protein misfolding and
      aggregation diseases and developing therapeutic strategies to these diseases
      demand that we gain mechanistic insight into behaviors and misbehaviors of
      proteins as they fold in vivo. We have developed a fluorescence approach using
      FlAsH labeling to study the thermodynamics of folding of a model beta-rich
      protein, cellular retinoic acid binding protein (CRABP) in Escherichia coli
      cells. The labeling approach has also enabled us to follow aggregation of a
      modified version of CRABP and chimeras between CRABP and huntingtin exon 1 with
      its glutamine repeat tract. In this article, we review our recent results using
      FlAsH labeling to study in-vivo folding and present new observations that hint at
      fundamental differences between the thermodynamics and kinetics of protein
      folding in vivo and in vitro.

PMID- 17206629
TI  - NMR analysis of G7-18NATE, a nonphosphorylated cyclic peptide inhibitor of the
      Grb7 adapter protein.
AB  - G7-18NATE is a nonphosphorylated, cyclic peptide that specifically inhibits the
      Grb7 adapter protein implicated in several pathways critical to cell
      proliferation and migration. It has been shown that G7-18NATE is able to compete
      with natural ligands for the Grb7 SH2 phosphotyrosine binding site, and to
      attenuate cell migration in a pancreatic cancer cell line. It is thus an
      important lead in the development of a selective inhibitor of Grb7 and potential
      novel anticancer therapeutics. The current study reports the solution properties
      of G7- 18NATE determined using NMR spectroscopy, in both water (pH 2-3) and
      phosphate buffer (pH 6.0), with 100 mM NaCl. The spectra reveal that G7-18NATE
      exists in two distinguishable conformational states on the NMR timescale, most
      likely due to cis-trans proline isomerization. In addition, the chemical shift
      data are consistent with a tendency of G7-18NATE to form a turn about the YDN
      motif, known to be important for binding, and suggest that this turn is
      stabilized in low salt and low pH conditions. Low NH temperature coefficients of
      Tyr-5 and Asn-7 amide protons may reflect their involvement in the formation of
      hydrogen bonds that stabilize such a turn. Overall, however, the peptide does not
      form a rigid structure, but exists in a highly flexible state in solution.
      Averaged 3JNH-H coupling constants and a lack of interresidue NOEs are
      characteristic of such peptide solution behavior. This suggests that there is
      scope for increasing the rigidity of the peptide that may enhance its binding
      affinity and specificity for Grb7.

PMID- 17206630
TI  - Peptides as transmembrane segments: decrypting the determinants for helix-helix
      interactions in membrane proteins.
AB  - Although the structural analysis of membrane proteins is advancing, an
      understanding of the basic principles that underlie their folding and assembly
      remains limited because of the high insolubility intrinsic to these molecules and
      concomitant challenges in obtaining crystals. Fortunately, from an experimental
      standpoint, membrane protein folding can be approximated as the rigid-body
      docking of pre-formed alpha-helical transmembrane segments one with another to
      form the final functional protein structure. Peptides derived from the sequences
      of native alpha-helical transmembrane segments and those that mimic their
      properties are therefore valuable in the experimental evaluation of protein
      folding within the membrane. Here we present an overview of the progress made in
      our laboratory and elsewhere in using peptide models toward defining the sequence
      requirements and forces stabilizing membrane protein folds.

PMID- 17206631
TI  - A new sequence representation as applied in better specificity elucidation for
      human immunodeficiency virus type 1 protease.
AB  - Factor analysis scales of generalized amino acid information (FASGAI) involving
      hydrophobicity, alpha and turn propensities, bulky properties, compositional
      characteristics, local flexibility, and electronic properties were derived from
      516 property parameters of 20-coded amino acids, and was then employed to
      represent sequence structures of 746 peptides with 8 amino acid residues.
      Cleavage site prediction models for human immunodeficiency virus type 1 protease
      by linear discriminant analysis and support vector machine with radial basis
      function kernel were constructed to identify if they could be cleaved or not, and
      were further utilized to investigate the cleavage specificity. These diversified
      properties, including the bulky properties, secondary conformation
      characteristics, electronic properties, and hydrophobicity at the first, the
      second, the fourth, the fifth, and the sixth residue, are possibly important
      factors in determining HIV PR cleavage or not. Particularly, maximal positive and
      negative influences result from the bulky properties of different sites. Further
      results from analysis of variance also likely reflect that the HIV PR recognizes
      diversified key properties of various sites in the octameric sequences.
      Satisfactory results show that FASGAI can not only be used to represent sequence
      structures of various functional peptides, but alsoprovide a potential feasible
      measure for exploring relationship between protein motif sequences and their
      functions.

PMID- 17206633
TI  - Safety and tolerability of concurrent natalizumab treatment for patients with
      Crohn's disease not in remission while receiving infliximab.
AB  - BACKGROUND: Natalizumab, a humanized monoclonal IgG(4) antibody to alpha4
      integrin, was investigated as a treatment of active Crohn's disease (CD). The
      safety of natalizumab given in combination with infliximab has not previously
      been studied. METHODS: Seventy-nine adult patients with active CD (Crohn's
      Disease Activity Index [CDAI] score > or = 150) despite ongoing infliximab
      treatment were randomized 2:1 to receive 3 intravenous infusions of natalizumab
      (300 mg; n = 52) or placebo (n = 27) every 4 weeks. Patients received infliximab
      (5 mg/kg) every 8 weeks for at least 10 weeks before randomization and throughout
      the study. The primary objective was to assess the short-term safety and
      tolerability of natalizumab in patients concurrently receiving infliximab.
      Secondary and tertiary objectives included measures of efficacy, health-related
      quality of life (HRQoL), and effects on inflammatory markers. A subset of
      patients also participated in a pharmacokinetic/pharmacodynamic (PK/PD) analysis
      of the effects of concurrent treatment. RESULTS: Incidence of adverse events
      (AEs) was similar in the treatment groups. AEs frequently reported in both groups
      were headache, CD exacerbation, nausea, and nasopharyngitis. No patient had a
      hypersensitivity-like reaction to natalizumab, whereas 4 patients (5%)
      experienced reactions to infliximab. Two patients (4%) developed anti-natalizumab
      antibodies; 10 patients (14%) developed anti-infliximab antibodies. The mean CDAI
      score decreased with natalizumab plus infliximab but was unchanged with
      infliximab alone (-37.7 versus +3.5; P = 0.084). Patients in both groups showed
      small increases in HRQoL (P = 0.811). No drug-drug interactions were noted.
      CONCLUSIONS: The combination of natalizumab plus infliximab was well tolerated.
      Several positive trends suggested that treating patients not in remission with
      infliximab plus natalizumab had greater efficacy than treatment with infliximab
      alone.

PMID- 17206634
TI  - Does colonoscopy cause increased ulcerative colitis symptoms?
AB  - BACKGROUND: Ulcerative colitis (UC) patients often report symptom flares after
      colonoscopy. However, this has not been documented in the literature. OBJECTIVES:
      1. Determine whether colonoscopy is associated with increased UC symptoms. 2.
      Determine whether there is a need for escalation of UC medications after
      colonoscopy. 3. Identify baseline variables associated with increased symptoms
      after colonoscopy. METHODS: Fifty-five outpatients with a history of UC, intact
      colon, and quiescent disease were enrolled in a prospective case-crossover study.
      Subjects were evaluated with the Simple Clinical Colitis Activity Index (SCCAI)
      before colonoscopy, 1 week and 4 weeks after colonoscopy. A mixed model analysis
      was used to accommodate nonindependence of repeated measurements on the same
      patients. RESULTS: Fifty-one (91%) subjects completed the study. Six subjects had
      clinical relapse defined by a score of 5 or greater on the SCCAI during the week
      after colonoscopy. Five subjects increased their 5-aminosalicylic acid (5-ASA)
      medications immediately postcolonoscopy, two of whom had a SCCAI 5 or greater.
      Multivariate modeling demonstrated a clear association between the week
      immediately after colonoscopy preparation and increased disease activity, with
      the time period being predictive of increased SCCAI (week 1 vs. week 4, P =
      0.0127). The baseline SCCAI (P value < 0.0001) and prednisone use (P = 0.0120)
      were predictive of increased SCCAI postcolonoscopy. Thiopurines (P < 0.001) were
      protective against increased symptoms. CONCLUSIONS: In our study, 1 in 8 subjects
      had UC relapse by SCCAI immediately postcolonoscopy, and 1 in 10 subjects
      required an increase in their 5-ASA medications. Clinicians should be cognizant
      of this effect of colonoscopy in patients with UC.

PMID- 17206635
TI  - Multidrug resistance gene-1 polymorphisms and resistance to cyclosporine A in
      patients with steroid resistant ulcerative colitis.
AB  - BACKGROUND: Cyclosporine A (CsA) is inconstantly effective in inducing remission
      in acute attacks of ulcerative colitis (UC) not responding to steroids. This
      study aimed to establish whether multidrug resistance gene (MDR)1 polymorphisms
      would be associated with CsA failure. PATIENTS AND METHODS: The distribution of
      the different genotypes of single nucleotide polymorphisms (SNP) G2677T/A and
      C3435T of MDR1 exons 21 and 26, respectively, was studied in 154 patients (mean
      age, 44 yr) who had received CsA to treat severe attacks of steroid resistant UC
      in 11 centers in France and Belgium. Patients were classified as CsA failure (n =
      50) when they needed colectomy within 30 days after CsA initiation. The SNPs were
      detected by use of a 5' nuclease allelic discrimination assay. RESULTS: There was
      a significant association between the G2677T/A polymorphism distribution (exon
      21) and the risk for CsA failure (P = 0.0001). The TT genotype of exon 21 was
      significantly associated with the risk compared with the two other genotypes
      (odds ratio, 3.77; 95% confidence interval, 1.42-9.97, P = 0.007). There was no
      significant association between the genotype C3435T distribution (exon 26) and
      the risk of CsA failure (P = 0.23). CONCLUSION: The TT genotype of exon 21 MDR1
      polymorphisms is associated with a higher risk of CsA failure in patients with
      steroid resistant UC. Further studies should be performed to establish whether
      other treatments could be more efficient to avoid surgery in this subset of
      patients.

PMID- 17206636
TI  - The prevalence of genetic and serologic markers in an unselected European
      population-based cohort of IBD patients.
AB  - BACKGROUND AND AIM: The aetiology of inflammatory bowel disease (IBD) is unknown,
      but it has become evident that genetic factors are involved in disease
      susceptibility. Studies have suggested a north-south gradient in the incidence of
      IBD, raising the question whether this difference is caused by genetic
      heterogeneity. We aimed to investigate the prevalence of polymorphisms in CARD15
      and TLR4 and occurrence of anti-Saccharomyces cerevisiae (ASCA) and
      antineutrophil cytoplasmic antibodies (pANCA) in a European population-based IBD
      cohort. METHODS: Individuals from the incident cohort were genotyped for three
      mutations in CARD15 and the Asp299gly mutation in TLR4. Levels of ASCA and pANCA
      were assessed. Disease location and behaviour at time of diagnosis was obtained
      from patient files. RESULTS: Overall CARD15 mutation rate was 23.9% for CD and
      9.6% for UC patients (P < 0.001). Mutations were less present in the Scandinavian
      countries (12.1%) versus the rest of Europe (32.8%) (P < 0.001). Overall
      population attributable risk was 11.2%. TLR4 mutation rate was 7.6% in CD, 6.7%
      in UC patients and 12.3% in healthy controls (HC), highest among South European
      CD patients and HC. ASCA was seen in 28.5% of CD patients with no north-south
      difference, and was associated with complicated disease. pANCA was most common in
      North European UC patients and not associated with disease phenotype. CONCLUSION:
      The prevalence of mutations in CARD15 varied across Europe, and was not
      correlated to the incidence of CD. There was no association between mutations in
      TLR4 and IBD. The prevalence of ASCA was relatively low; however related to
      severe CD.

PMID- 17206637
TI  - The Luebeck interview for psychosocial screening in patients with inflammatory
      bowel disease.
AB  - BACKGROUND: Psychosocial factors play an important role in the course of
      inflammatory bowel disease (IBD). However, a simple, valid psychosocial screening
      instrument that is suitable for short patient-physician contacts does not exist.
      Therefore, the Luebeck semistructured Interview for Psychosocial Screening was
      developed as a rating tool for psychosocial stress in IBD patients (LIPS-IBD).
      METHOD: The entire interview requires approximately 10 minutes. Interrater
      reliability was tested. Depression, anxiety, social support, impact of the
      disease, global level of psychosocial stress, and demand for psychosocial support
      were rated in 92 patients with IBD on 5 point Likert scales. Patients from the in
      and out-patient clinic for gastroenterology were included. In addition, patients
      filled out self-report questionnaires regarding depression, anxiety, social
      support, and impact of the disease. Indices of disease activity (Colitis Activity
      Index, Crohn's Disease Activity Index) were recorded. RESULTS: Both patients and
      physicians found the interview feasible. Reliability was good, with interrater
      reliability ranging from .76 to .94. Convergence with self-report instruments was
      also high (r = .5-.6). Ratings of depression and impact of the disease were
      correlated with indices of disease activity. DISCUSSION: LIPS helps to identify
      patients with high levels of psychosocial stress and provide them with more
      detailed psychologic assessments. It was found to be a suitable instrument for
      daily clinical routine. It is potentially a valuable screening tool to obtain
      reliable, valid, and useful information in daily practice in IBD treatment
      settings.

PMID- 17206638
TI  - Natural history of bone metabolism and bone mineral density in children with
      inflammatory bowel disease.
AB  - BACKGROUND: In children with inflammatory bowel disease (IBD) it is not known
      whether reductions in bone mineral density (BMD) are a consequence of bone
      turnover alterations and if BMD improves with treatment. METHODS: In a cohort of
      children with IBD, we prospectively measured indicators of bone remodeling, body
      mass index (BMI), disease activity, intact parathyroid hormone, serum IL-6, and
      insulin-like growth factor-I at diagnosis and then every 6 months for 2 years.
      BMD was determined annually using dual x-ray absorptiometry (DXA). BMD Z-scores
      were calculated using height/age. Baseline measurements and calcium intake were
      compared with a group of age- and sex-matched healthy children. RESULTS: We
      observed that at diagnosis total body BMD Z-score (mean +/- SD) was -0.78 +/-
      1.02 for Crohn's disease (CD, n = 58), -0.46 +/- 1.14 for ulcerative colitis (UC,
      n = 18), and -0.17 +/- 0.95 for control (CL, n = 49) (P < 0.01, CD versus CL). In
      CD, a BMD Z-score <-1.0 was associated with lower BMI and higher serum IL-6.
      Patients with CD and UC had low bone turnover. Activation of bone formation
      paralleled clinical improvement, but BMC gain was less than expected over the 2
      year study period, especially in CD. Prednisone use did not correlate with low
      BMD. CONCLUSIONS: Decreased bone turnover occurs in children newly diagnosed with
      IBD. Although indicators of osteoblast activity increase with clinical
      improvement, bone mineral accrual does not accelerate. Children with low BMI may
      be considered for BMD screening, since they are at risk for low bone mass.

PMID- 17206639
TI  - Azathioprine and mesalazine-induced effects on the mucosal flora in patients with
      IBD colitis.
AB  - BACKGROUND: The impact of azathioprine and 5-aminosalicylic acid (5-ASA) on the
      innate immunity and mucosal flora is unknown. The study investigated the
      influence of IBD treatment on the concentrations and spatial organization of
      mucosal bacteria using fluorescence in situ hybridization with 16s r-RNA
      targeting probes. METHODS: We prospectively investigated colonoscopic biopsies
      from five groups of 20 subjects each: patients with ulcerative or indeterminate
      colitis treated with azathioprine (group 1), azathioprine and 5-ASA (group 2), 5
      ASA (group 3), untreated IBD (group 4), and healthy controls. RESULTS: The
      elevated numbers of leukocytes in mucus of IBD patients were reduced nearly to
      norm in patients treated with azathioprine alone. In contrast, 5-ASA therapy had
      no influence on mucus leukocyte migration and was associated with the lowest
      concentrations of mucosal bacteria of all IBD groups. The suppressed migration of
      leukocytes in azathioprine-treated patients was accompanied by a 28-fold higher
      concentration of mucosal bacteria when compared with the 5-ASA group or a 1000
      fold increase when compared with healthy controls. The percent of the epithelial
      surface covered with adherent bacteria (P < 0.001) and the amenability of mucosal
      bacteria (P = 0.01) were also significantly increased in the azathioprine-treated
      group compared with all other IBD groups. The patients receiving both 5-ASA and
      azathioprine did not differ statistically from untreated IBD patients either in
      mucus leukocyte migration or in bacterial concentrations. CONCLUSIONS:
      Azathioprine and 5-ASA induce opposite effects on the mucus barrier. Concomitant
      therapy of 5-ASA and azathioprine mutually neutralizes the effects of both on the
      mucosal flora and the barrier function.

PMID- 17206640
TI  - Glutathione-S-transferase genotypes and the adverse effects of azathioprine in
      young patients with inflammatory bowel disease.
AB  - BACKGROUND: Adverse drug reactions to azathioprine, the prodrug of 6
      mercaptopurine, occur in 15%-38% of patients and the majority are not explained
      by thiopurine-S-methyltransferase (TPMT) deficiency. Azathioprine is known to
      induce glutathione depletion and consumption of glutathione is greater in cells
      with high glutathione-S-transferase (GST) activity compared with those with low
      activity; moreover, some reports indicate that GST might play a direct role in
      the reaction of glutathione with azathioprine. The association between
      polymorphisms of GST-M1, GST-P1, GST-T1, and TPMT genes and the adverse effects
      of azathioprine was therefore investigated. METHODS: Seventy patients with
      inflammatory bowel disease (IBD), treated with azathioprine, were enrolled and
      clinical data were retrospectively determined. TPMT and GST genotyping were
      performed by polymerase chain reaction (PCR) assays on DNA extracted from blood
      samples. RESULTS: Fifteen patients developed adverse effects (21.4%); there was a
      significant underrepresentation of the GST-M1 null genotype among patients
      developing adverse drug reactions to azathioprine (odds ratio [OR] = 0.18, 95%
      confidence interval [CI] = 0.037-0.72, P = 0.0072) compared with patients who did
      not develop adverse effects. Patients heterozygous for TPMT mutations presented a
      marginally significant increased probability of developing adverse effects (OR =
      6.38, 95% CI = 0.66-84.1, P = 0.062). Moreover, among the 55 patients who did not
      develop adverse effects, there was a significant underrepresentation of the GST
      M1 null genotype among patients who displayed lymphopenia as compared with those
      that did not display this effect of azathioprine (OR = 0.15, 95% CI = 0.013-1.08,
      P = 0.032). CONCLUSION: Patients with IBD with a wildtype GST-M1 genotype present
      increased probability of developing adverse effects and increased incidence of
      lymphopenia during azathioprine treatment.

PMID- 17206641
TI  - Predictive value of mucosal TNF-alpha transcripts in steroid-refractory Crohn's
      disease patients receiving intensive immunosuppressive therapy.
AB  - BACKGROUND: Concentrations of proinflammatory cytokines are increased in the
      intestinal mucosa of patients with active Crohn's disease (CD). In a prospective
      study we investigated whether cytokines can predict long-term remission (>6
      months) in patients with steroid-refractory CD receiving treatment with
      infliximab or cyclophosphamide, followed by azathioprine or methotrexate.
      METHODS: Cytokine transcripts were quantified using real-time polymerase chain
      reaction (PCR) in mucosal biopsies from 19 patients with active, steroid
      refractory CD before and 8 weeks after initiation of therapy. Patients were
      treated with cyclophosphamide (monthly treatment of 750 mg cyclophosphamide
      intravenously) or infliximab (5 mg/kg body weight) and were followed until
      relapse of the disease. Statistical analysis was performed to identify predictive
      factors to discriminate between patients with or without long-term remission.
      RESULTS: Seventeen out of 19 patients achieved remission of the disease, two
      patients were nonresponders, while six out of 17 patients exhibited an early
      recurrence. Pretreatment TNF-alpha, IL-18, MRP-14, and IL-8 transcripts were
      significantly correlated with long-term remission. While several cytokines, most
      importantly MMP-1, determined after 8 weeks were able to predict patients
      achieving long-term remission, only a decrease of TNF-alpha levels after 8 weeks
      was predictive. Overall, statistical analysis identified lower pretreatment TNF
      alpha levels as the strongest predictor of long-term remission among baseline
      variables. CONCLUSIONS: Quantification of mucosal TNF-alpha transcripts prior to
      therapy allows identification of patients achieving long-term remission upon
      immunosuppression with infliximab or cyclophosphamide. Real-time PCR might have
      considerable potential in the analysis of disease activity and subsequent
      clinical management of patients with immunosuppressive therapies.

PMID- 17206642
TI  - Macrophage migration inhibitory factor (MIF) -173G/C promoter polymorphism
      influences upper gastrointestinal tract involvement and disease activity in
      patients with Crohn's disease.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is a proinflammatory
      cytokine with increased expression in inflammatory bowel disease. The aim of the
      study was to analyze the role of the MIF -173G/C single nucleotide polymorphism
      in Crohn's disease (CD). METHODS: Using restriction fragment length polymorphism
      analysis, genomic DNA of 198 patients with CD and 159 unrelated controls was
      analyzed for the -173G/C SNP in the MIF promoter region. Colonic MIF mRNA
      expression was measured by quantitative polymerase chain reaction (PCR), serum
      MIF levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Thirty-six of
      the 146 G/G wildtype carriers (24.7%) but only 3 of the 45 G/C heterozygotes
      (6.7%) and only 1 of the C/C homozygotes (14.3%) were diagnosed with upper
      gastrointestinal tract involvement (P = 0.009, odds ratio [OR] = 0.22, 95%
      confidence interval [CI], 0.06-0.75 for wildtype versus hetero- and homozygous
      carriers). This result was confirmed in a second prospective study, in which all
      patients diagnosed with upper gastrointestinal involvement (n = 13) were G/G
      wildtype carriers (P = 0.01 versus controls). All patients (n = 12; 100%) with a
      Crohn's disease activity index (CDAI) > 300 were G/G wildtype carriers compared
      to only 65.6% wildtype carriers in the group with a CDAI < 150 (P = 0.016). MIF
      is expressed in the colonic mucosa of CD patients and intestinal epithelial cells
      but its mRNA expression does not correlate with the degree of inflammation and is
      not upregulated by proinflammatory cytokines. In CD, MIF serum levels are not
      influenced by the MIF -173G/C polymorphism. CONCLUSIONS: The MIF -173G/C
      polymorphism appears to be a factor contributing to a particular CD phenotype
      characterized by protection against upper gastrointestinal tract involvement and
      severe disease activity.

PMID- 17206643
TI  - Lactobacillus fermentum attenuates the proinflammatory effect of Yersinia
      enterocolitica on human epithelial cells.
AB  - BACKGROUND: Lactobacilli represent a major component of the human microbiota. In
      this study we investigated whether and how Lactobacillus fermentum inhibits the
      proinflammatory responses of human epithelial cells on Yersinia enterocolitica
      infection. METHODS: Human epithelial cells were exposed to Y. enterocolitica pYV(
      ) or L. fermentum or to both strains, combinations of heat-killed L. fermentum or
      supernatant of L. fermentum cultures and Y. enterocolitica. The modulation of Y.
      enterocolitica induced IL-8 levels in the culture supernatants was determined and
      activation of Rac, p38, and NF-kappaB was investigated. RESULTS: Exposure of
      human epithelial cells to L. fermentum does not induce NF-kappaB activation and
      subsequent IL-8 secretion in HeLa cells, whereas Y. enterocolitica induces NF
      kappaB activation and high levels of IL-8. Viable L. fermentum, supernatant of L.
      fermentum cultures, but not heat-killed L. fermentum, inhibited IL-8 secretion of
      HeLa cells triggered by Y. enterocolitica. Lactobacillus fermentum-exposed HeLa
      cells showed decreased Rac, p38, and NF-kappaB activation after Y. enterocolitica
      infection. Treatment of L. fermentum supernatants with phospholipase C abolished
      the inhibitory effect, indicating that a secreted phospholipid mediates the
      antiinflammatory properties of L. fermentum. Adhesion to or invasion of Y.
      enterocolitica into epithelial cells was not altered by coincubation with L.
      fermentum. CONCLUSION: Our results lead to the conclusion that L. fermentum
      inhibits the Y. enterocolitica-induced IL-8 production by a possibly secreted
      phospholipid of <10 kDa molecular weight. These data suggest that L. fermentum
      may have probiotic properties modulating intestinal inflammatory responses and
      might offer new therapeutic strategies in the treatment of intestinal
      inflammatory diseases.

PMID- 17206644
TI  - Treatment of irritable bowel syndrome in outpatients with inflammatory bowel
      disease using a food and beverage intolerance, food and beverage avoidance diet.
AB  - Irritable bowel syndrome (IBS) in the outpatient with chronic inflammatory bowel
      disease (IBD) is a difficult but important challenge to recognize and treat. It
      is very helpful to have effective treatment approaches for IBS that are practical
      and use minimal medications. Because of the underlying chronic inflammation in
      IBD, IBS symptoms occur with increased frequency and severity, secondary to
      increased hypersensitivity to foods and beverages that stimulate the
      gastrointestinal tract. This paper discusses how to treat IBS in the IBD
      outpatient, with emphasis on using a food and beverage intolerance, avoidance
      diet. The adverse effects of many foods and beverages are amount dependent and
      can be delayed, additive, and cumulative. The specific types of foods and
      beverages that can induce IBS symptoms include milk and milk containing products;
      caffeine containing products; alcoholic beverages; fruits; fruit juices; spices;
      seasonings; diet beverages; diet foods; diet candies; diet gum; fast foods;
      condiments; fried foods; fatty foods; multigrain breads; sourdough breads;
      bagels; salads; salad dressings; vegetables; beans; red meats; gravies; spaghetti
      sauce; stews; nuts; popcorn; high fiber; and cookies, crackers, pretzels, cakes,
      and pies. The types of foods and beverages that are better tolerated include
      water; rice; plain pasta or noodles; baked or broiled potatoes; white breads;
      plain fish, chicken, turkey, or ham; eggs; dry cereals; soy or rice based
      products; peas; applesauce; cantaloupe; watermelon; fruit cocktail; margarine;
      jams; jellies; and peanut butter. Handouts that were developed based upon what
      worsens or helps IBS symptoms in patients are included to help patients learn
      which foods and beverages to avoid and which are better tolerated.

PMID- 17206645
TI  - Matrix metalloproteinases in inflammatory bowel disease: boon or a bane?
AB  - Matrix metalloproteinases (MMPs) are a family of Zn(2+)-dependent extracellular
      matrix (ECM) degrading endopeptidases that share common functional domains,
      activation mechanisms, and collectively have the capacity to degrade all types of
      ECM proteins. In addition to playing a central role in ECM turnover, MMPs
      proteolytically activate or degrade a variety of nonmatrix substrates including
      chemokines, cytokines, growth factors, and junctional proteins. Thus, they are
      increasingly recognized as critical players in inflammatory response. Indeed,
      accumulating data from several studies indicate that they are the predominant
      proteases involved in the pathogenesis of inflammatory bowel disease (IBD) via
      their influence on the function and migration of inflammatory cells, mucosal
      ulceration, as well as matrix deposition and degradation. Some MMPs are
      constitutively expressed and play a protective role in IBD through their effect
      on cellular homeostasis, while others are induced during inflammation-mediated
      tissue damage. This article focuses on the role of the various MMPs in IBD,
      discussing their physiologic and pathogenetic role in the context of intestinal
      defense, mucosal inflammatory response, and immune cell-epithelial interaction.

PMID- 17206646
TI  - Hypothesis about mechanisms through which nicotine might exert its effect on the
      interdependence of inflammation and gut barrier function in ulcerative colitis.
AB  - Ulcerative colitis (UC) is characterized by impairment of the epithelial barrier
      and the formation of ulcer-type lesions, which result in local leaks and
      generalized alterations of mucosal tight junctions. Ultimately, this results in
      increased basal permeability. Although disruption of the epithelial barrier in
      the gut is a hallmark of inflammatory bowel disease and intestinal infections, it
      remains unclear whether barrier breakdown is an initiating event of UC or rather
      a consequence of an underlying inflammation, evidenced by increased production of
      proinflammatory cytokines. UC is less common in smokers, suggesting that the
      nicotine in cigarettes may ameliorate disease severity. The mechanism behind this
      therapeutic effect is still not fully understood, and indeed it remains unclear
      if nicotine is the true protective agent in cigarettes. Nicotine is metabolized
      in the body into a variety of metabolites and can also be degraded to form
      various breakdown products. It is possible these metabolites or degradation
      products may be the true protective or curative agents. A greater understanding
      of the pharmacodynamics and kinetics of nicotine in relation to the immune system
      and enhanced knowledge of gut permeability defects in UC are required to
      establish the exact protective nature of nicotine and its metabolites in UC. This
      review suggests possible hypotheses for the protective mechanism of nicotine in
      UC, highlighting the relationship between gut permeability and inflammation, and
      indicates where in the pathogenesis of the disease nicotine may mediate its
      effect.

PMID- 17206647
TI  - Why good pouches go bad.

PMID- 17206648
TI  - Synergistic effect of methotrexate and infliximab on activated lymphocyte
      apoptosis.

PMID- 17206649
TI  - Litaf/Simple protein is increased in intestinal tissues from patients with CD and
      UC, but is unlikely to function as a transcription factor.

PMID- 17206650
TI  - Identification of neuropeptide Y cleavage products in human blood to improve
      metabolic stability.
AB  - Regulatory, receptor-binding peptides are considered as the agents of choice for
      diagnostic imaging and therapy of cancers, because their receptors are
      overexpressed in various human cancer cells. It has been recently indicated that
      there is a putative role of NPY in breast tumors. The expression of the two best
      investigated NPY receptor subtypes, Y1 and Y2, in breast tissue shows predominant
      occurrence of the Y1 receptor subtype in tumors, whereas Y2 receptors are found
      in nonproliferative tissue. To investigate the usefulness of NPY analogs for
      tumor diagnosis and therapy, we investigated the metabolic stability of receptor
      selective NPY analogs in human blood plasma. NPY analogs were synthesized by
      Fmoc/t-Bu solid-phase strategy. Prior to the cleavage of peptides from the resin,
      they were labeled with 5(6)-carboxyfluorescein (CF) either at the N-terminus or
      at the side chain of Lys4. For the metabolic stability study, the digestion of
      peptides was monitored by HPLC and the cleavage products were identified by MALDI
      ToF mass spectrometry. The data showed that full-length [Phe7, Pro34]NPY analogs,
      which show high binding affinity to Y1 receptors are enzymatically more stable
      than centrally truncated analogs, which show high binding affinity to Y2
      receptors. Furthermore, the N-terminally CF-labeled Y1 and Y2 receptor-selective
      peptides were found to be enzymatically more resistant than their counterparts
      containing the CF label at Lys4 side chain.

PMID- 17206651
TI  - Rapid and accurate measurement for phase-change optical recording bits.
AB  - Conducting atomic force microscopy (CAFM) and scanning surface potential
      microscopy (SSPM) have been used to image the phase-change optical recording
      bits. Commercially available digital versatile discs (DVD) + rewritable (RW) with
      initialization process were measured in experiments. Comparing the measurement
      results of both, the measurement resolution of CAFM is far superior to that of
      SSPM. With the DVD + RW disc rotating at a linear speed of 3.5 m/s, appropriate
      writing laser power range, may be precisely identified by CAFM as 10-15 mW. This
      is sufficient to verify the high-resolution recording bits research method. This
      new method may also be applied to the development of new types of phase-change
      recording materials.

PMID- 17206652
TI  - Studies on the importance of sympathetic innervation, adrenergic receptors, and a
      possible local catecholamine production in the development of patellar
      tendinopathy (tendinosis) in man.
AB  - Changes in the patterns of production and in the effects of signal substances may
      be involved in the development of tendinosis, a chronic condition of pain in
      human tendons. There is no previous information concerning the patterns of
      sympathetic innervation in the human patellar tendon. In this study, biopsies of
      normal and tendinosis patellar tendons were investigated with immunohistochemical
      methods, including the use of antibodies against tyrosine hydroxylase (TH) and
      neuropeptide Y, and against alpha1-, alpha2A-, and beta1-adrenoreceptors. It was
      noticed that most of the sympathetic innervation was detected in the walls of the
      blood vessels entering the tendon through the paratendinous tissue, and that the
      tendon tissue proper of the normal and tendinosis tendons was very scarcely
      innervated. Immunoreactions for adrenergic receptors were noticed in nerve
      fascicles containing both sensory and sympathetic nerve fibers. High levels of
      these receptors were also detected in the blood vessel walls; alpha1
      adrenoreceptor immunoreactions being clearly more pronounced in the tendinosis
      tendons than in the tendons of controls. Interestingly, immunoreactions for
      adrenergic receptors and TH were noted for the tendon cells (tenocytes),
      especially in tendinosis tendons. The findings give a morphological correlate for
      the occurrence of sympathetically mediated effects in the patellar tendon and
      autocrine/paracrine catecholamine mechanisms for the tenocytes, particularly, in
      tendinosis. The observation of adrenergic receptors on tenocytes is interesting,
      as stimulation of these receptors can lead to cell proliferation, degeneration,
      and apoptosis, events which are all known to occur in tendinosis. Furthermore,
      the results imply that a possible source of catecholamine production might be the
      tenocytes themselves

PMID- 17206656
TI  - Strong and weak hydrogen bonds in the protein-ligand interface.
AB  - The characteristics of N--H...O, O--H...O, and C--H...O hydrogen bonds and other
      weak intermolecular interactions are analyzed in a large and diverse group of 251
      protein-ligand complexes using a new computer program that was developed in-house
      for this purpose. The interactions examined in the present study are those which
      occur in the active sites, defined here as a sphere of 10 A radius around the
      ligand. Notably, N--H...O and O--H...O bonds tend towards linearity.
      Multifurcated interactions are especially common, especially multifurcated
      acceptors, and the average degree of furcation is 2.6 hydrogen bonds per furcated
      acceptor. A significant aspect of this study is that we have been able to assess
      the reliability of hydrogen bond geometry as a function of crystallographic
      resolution. Thresholds of 2.3 and 2.0 A are established for strong and weak
      hydrogen bonds, below which hydrogen bond geometries may be safely considered for
      detailed analysis. Interactions involving water as donor or acceptor, and C-
      H...O bonds with Gly and Tyr as donors are ubiquitous in the active site. A
      similar trend was observed in an external test set of 233 protein-ligand
      complexes belonging to the kinase family. Weaker interactions like X--H...pi (X =
      C, N, O) and those involving halogen atoms as electrophiles or nucleophiles have
      also been studied. We conclude that the strong and weak hydrogen bonds are
      ubiquitous in protein-ligand recognition, and that with suitable computational
      tools very large numbers of strong and weak intermolecular interactions in the
      ligand-protein interface may be analyzed reliably. Results confirm earlier trends
      reported previously by us but the extended nature of the present data set mean
      that the observed trends are more reliable.

PMID- 17206657
TI  - Variability of the recessive oculopharyngeal muscular dystrophy phenotype.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is usually transmitted as an autosomal
      dominant trait and characterized by an expansion from 6 to 8 or more GCG/GCA
      repeats in the poly-(A) binding protein nuclear 1 (PABPN1) gene on chromosome
      14q11. Autosomal-recessive OPMD with a homozygous (GCG)7 expansion of PABPN1 has
      only been described in two Canadian patients, who showed a comparably mild
      phenotype, suggesting that it is less severe than the dominant form. We
      clinically and genetically characterized the first two reported cases of
      autosomal-recessive OPMD in Europe. Remarkably, both patients revealed severe and
      diverse phenotypes, with an unusual onset and atypical clinical course in one
      patient. Former studies found a 1%-2% frequency of the (GCG)7 allele, which
      theoretically produces an incidence of 1:10,000 of autosomal-recessive OPMD in
      the general population. We conclude that the apparent rarity of the autosomal
      recessive form of OPMD may be due to the fact that genetic testing is generally
      administered only to patients with typical clinical features or a positive family
      history.

PMID- 17206658
TI  - Urtica ferox neuropathy.
AB  - A 21-year-old student developed an acute, symmetrical, predominantly motor
      polyneuropathy within 48 h of walking through a patch of nettles (Urtica ferox).
      Two companions had similar but less severe symptoms. Nerve conduction studies
      demonstrated markedly reduced compound muscle action potentials and prolonged
      distal motor latencies. Recovery occurred over a period of a few weeks. This case
      demonstrates that cutaneous exposure to Urtica ferox can cause an acute
      polyneuropathy and that its stinging hairs contain an unidentified neurotoxin.

PMID- 17206659
TI  - Contact patterns between helices and strands of sheet define protein folding
      patterns.
AB  - Comparing and classifying protein folding patterns allows organizing the known
      structures and enumerating possible protein structural patterns including those
      not yet observed. We capture the essence of protein folding patterns in a concise
      tableau representation based on the order and contact patterns of secondary
      structures: helices and strands of sheet. The tableaux are intelligible to both
      humans and computers. They provide a database, derived from the Protein Data
      Bank, mineable in studies of protein architecture. Using this database, we have:
      (i) determined statistical properties of secondary structure contacts in an
      unbiased set of protein domains from ASTRAL, (ii) observed that in 98% of cases,
      the tableau is a faithful representation of the folding pattern as classified in
      SCOP, (iii) demonstrated that to a large extent the local structure of proteins
      indicates their complete folding topology, and (iv) studied the use of the
      representation for fold identification.

PMID- 17206660
TI  - Secondary structure length as a determinant of folding rate of proteins with two-
      and three-state kinetics.
AB  - We present a simple method for determining the folding rates of two- and three
      state proteins from the number of residues in their secondary structures
      (secondary structure length). The method is based on the hypothesis that two- and
      three-state foldings share a common pattern. Three-state proteins first condense
      into metastable intermediates, subsequent forming of alpha-helices, turns, and
      beta-sheets at slow rate-limiting step. The folding rate of such proteins
      anticorrelate with the length of these beta-secondary structures. It is also
      assumed that in two-state folding, rapidly folded alpha-helices and turns may
      facilitate formation of fleeting unobservable intermediates and thus show two
      state behavior. There is an inverse relationship between the folding rate and the
      length of beta-sheets and loops. Our study achieves 94.0 and 88.1% correlations
      with folding rates determined experimentally for 21 three- and 38 two-state
      proteins, respectively, suggesting that protein-folding rates are determined by
      the secondary structure length. The kinetic kinds are selected on the basis of a
      competitive formation of hydrophobic collapse and alpha-structure in early
      intermediates.

PMID- 17206661
TI  - Sources of axonal calcium loading during in vitro ischemia of rat dorsal roots.
AB  - A detailed understanding of injury mechanisms in peripheral nerve fibers will
      help guide successful design of therapies for peripheral neuropathies. This study
      was therefore undertaken to examine the ionic mechanisms of Ca2+ overload in
      peripheral myelinated fibers subjected to chemical inhibition of energy
      metabolism. Myelinated axons from rat dorsal roots were co-loaded with Ca2+
      sensitive (Oregon Green BAPTA-1) and Ca2+-insensitive (Alexa Fluor 594) dextran
      conjugated fluorophores and imaged using confocal laser scanning microscopy.
      Axoplasmic regions were clearly outlined by the Ca2+-insensitive dye, from which
      axonal Ca2+-dependent fluorescence changes (FCa.ax) were measured. Block of Na+
      K+ ATPase (ouabain), opening of Na+ channels (veratridine), and inhibiting energy
      metabolism (iodoacetate + NaN3) caused a rapid rise in FCa.ax to 96% above
      control after 30 min. Chemical ischemia (iodoacetate + NaN3) caused a more
      gradual increase in FCa.ax (54%), which was almost completely dependent on bath
      Ca2+, indicating that most of the Ca2+ accumulation occurred via influx across
      the axolemma. Na+ channel block (tetrodotoxin) reduced ischemic FCa.ax rise
      (14%); however, inhibition of L-type Ca2+ channels (nimodipine) had no effect
      (60%). In contrast, Na+-Ca2+ exchange inhibition (KB-R7943) significantly reduced
      ischemic FCa.ax rise (18%). Together our results indicate that the bulk of Ca2+
      overload in injured peripheral myelinated axons occurs via reverse Na+-Ca2+
      exchange, driven by axonal Na+ accumulation through voltage-gated tetrodotoxin
      sensitive Na+ channels. This mechanism may represent a viable therapeutic target
      for peripheral neuropathies.

PMID- 17206662
TI  - Myasthenia gravis and Lambert-Eaton myasthenic syndrome in the same patient.
AB  - An 18-year-old-woman developed symptoms of generalized myasthenia gravis (MG).
      Antibodies to the acetylcholine receptor were found in her serum, but
      electrodiagnostic testing showed abnormalities typical of the Lambert-Eaton
      myasthenic syndrome (LEMS). Following thymectomy, the thymus gland showed thymic
      hyperplasia typical of MG, and the patient responded to treatment with 3,4
      diaminopyridine and pyridostigmine. There have been few reports in the literature
      of MG and LEMS coexisting in the same patient. In this case, electrodiagnostic
      tests, antibody studies, thymus pathology, and response to treatment suggest that
      both disorders contributed to the patient's symptoms. Thymic hyperplasia, so far
      only known to be associated with MG, provides strong evidence that both diseases
      were symptomatic.

PMID- 17206663
TI  - Refractory and infected pyoderma gangrenosum in a patient with ulcerative
      colitis: response to infliximab.

PMID- 17206664
TI  - Study of expression patterns and levels of neurotrophins and neurotrophin
      receptors in ulcerative colitis.
AB  - BACKGROUND: Neurotrophins may be involved in ulcerative colitis (UC). Yet, it is
      unclear whether if their effects should be blocked. METHODS: In this study, the
      neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor
      (BDNF) and their receptors were examined by immunohistochemistry, ELISA, and RT
      PCR. RESULTS: BDNF immunoreaction was detected in nerve structures in particular,
      and NGF immunoreaction was detected in lamina propria cells. Cellular NGF
      immunoreaction was generally observed to be higher in the mucosa of UC patients
      than in the controls. In addition, UC patients demonstrated significantly higher
      p75 immunoreaction (P = 0.010) in lamina propria cells. The controls expressed
      significantly higher BDNF immunoreaction in the nerve structures than did UC
      patients (P = 0.000). However, the UC group showed marked interindividual
      variation in expression of neurotrophins and neurotrophin receptors. This
      included variation at the mRNA level for NGF. Differences with the controls were
      most pronounced in UC specimens demonstrating great infiltration of inflammatory
      cells and marked tissue derangement. Corticosteroid treatment seemed to affect
      neurotrophin production in lamina propria cells but not in nerve structures.
      These observations demonstrate that up-regulation and down-regulation of
      neurotrophins occur in different structural components in response to the disease
      process. Massive inflammation seemed to be correlated with decreased neurotrophin
      immunoreaction in nerve structures, but there was a tendency toward increased
      neurotrophin production in lamina propria cells. CONCLUSIONS: Our study shows
      that UC patients are not a uniform group in their expression of neurotrophins, a
      fact that should be considered when discussing therapeutic interventions.

PMID- 17206665
TI  - Expression and functional characterization of FOXP3+ CD4+ regulatory T cells in
      ulcerative colitis.
AB  - BACKGROUND: CD4+CD25+ regulatory T cells (TR) can prevent or treat experimental
      murine colitis but little is known about their potential role in human
      inflammatory bowel disease (IBD). FOXP3 is a transcription factor that plays a
      critical role in the development and function of CD4+CD25+ TR. The aim of this
      study was to examine the presence and functional characteristics of TR cells in
      colonic lymphoid tissues in patients with ulcerative colitis (UC). METHODS: FOXP3
      expression was assessed by flow cytometry, immunohistochemistry, and reverse
      transcriptase polymerase chain reaction (RT-PCR). Functional characterization of
      CD4+CD25+ cells was analyzed by suppression of proliferation and secretion of
      cytokines by cocultured effector CD4+CD25- T cells. RESULTS: FOXP3 +CD4+ T cells
      are increased in the lamina propria (LP) of inflamed and noninflamed areas of UC
      colon compared to normal colon. CD4+CD25+ T cells in UC mesenteric lymph nodes
      (MLN) express FOXP3 mRNA and protein and suppress the proliferation of autologous
      MLN CD4+CD25 T cells. The suppressor activity of MLN CD4+CD25+ T cells is cell
      contact-dependent but cytokine-independent. In addition, CD4+CD25+ T cells
      potently suppress the production of both Thl (IFN-gamma, IL-2) and Th2 (IL-5, IL
      13) cytokines by cocultured CD4+CD25 T cells. FOXP3' cells localized in the T
      cell-rich areas of MLN and occasionally present in the follicles. CONCLUSIONS:
      There is an expansion of FOXP3+CD4+ T cells in mucosal lymphoid tissues in UC.
      CD4+CD25+ isolated from UC MLN express FOXP3 and display features of TR cells in
      spite of active mucosal inflammation. These data suggest that their suppressor
      activity may be abrogated in vivo or they are unable to counterbalance the
      chronic mucosal inflammation in UC.

PMID- 17206666
TI  - Use of an intravascular thrombectomy device to treat life-threatening venous
      thrombosis in a patient with Crohn's disease and G20210A prothrombin gene
      mutation.

PMID- 17206667
TI  - Genetics of the innate immune response in inflammatory bowel disease.
AB  - The discovery of nucleotide-binding oligomerization domain 2/caspase recruitment
      domain-containing protein 15 (NOD2/CARD15) as the first susceptibility gene in
      Crohn's disease (CD) has shifted the focus of research into the pathogenesis of
      inflammatory bowel disease (IBD) firmly to the innate immune response and the
      integrity of the epithelial barrier. The subsequent implication in IBD of variant
      alleles of OCTN, DLG5, MDR1, and TLRs has provided further support for a new,
      more complex model of innate immunity function in the gastrointestinal tract. In
      this review, we examine the recent advances in our understanding of the influence
      of genetics of the innate immune response on IBD. We will focus on germline
      variation of genes encoding pathogen-recognition receptors, proteins involved in
      epithelial homeostasis and secreted antimicrobial proteins.

PMID- 17206668
TI  - Contribution of genetic and environmental factors in the pathogenesis of Crohn's
      disease in a large family with multiple cases.
AB  - BACKGROUND: A large family of Moroccan immigrants was investigated. In this
      family the father developed Crohn's disease (CD) after moving from Morocco to
      Belgium and successively 4 of his 8 children subsequently developed CD. There was
      no previous history of familial CD. METHODS: The family was interviewed at their
      home and an elaborated questionnaire was completed. The food and sanitation
      characteristics of the family were investigated. Moreover, serological markers
      were tested in all family members, including ASCA, ASCAg, ALCA, ACCA, Omp, and
      ANCA, using enzyme-linked immunosorbent assay and indirect immunofluorescence.
      Genetic variants in CARD15, TLR4, NOD1, CARD8, and DLG5 associated with CD were
      tested as well. The complete medical history of all patients was reviewed.
      RESULTS: There were no known genetic variants associated with CD in this family.
      None of the serological antibodies could discriminate between patients and
      unaffected family members, although the antibody titers were higher in diseased
      family members as compared with the healthy family members. CONCLUSION: The
      occurrence of 5 new cases of CD within 1 Moroccan family after immigration to
      Belgium cannot be explained by the known genetic susceptibility factors, and thus
      suggests a major environmental factor probably not related to sanitation in
      childhood.

PMID- 17206670
TI  - Is the incidence of inflammatory bowel disease in the developed countries
      increasing again? Is that surprising?

PMID- 17206669
TI  - Patchy distribution of mucosal lesions in ileal Crohn's disease is not linked to
      differences in the dominant mucosa-associated bacteria: a study using
      fluorescence in situ hybridization and temporal temperature gradient gel
      electrophoresis.
AB  - BACKGROUND: The mucosa-associated bacteria (MAB) are suspected of being involved
      in the pathogenesis of Crohn's disease. We analyzed and compared the MAB in
      noninflamed and inflamed ileal mucosa of Crohn's disease patients (n = 22).
      METHODS: Tissue samples from the inflamed ileal mucosa and from the adjacent
      noninflamed ileal mucosa were taken from surgical resection specimens. The MAB
      were investigated using fluorescence in situ hybridization with 7 group-specific
      probes and temporal temperature gradient gel electrophoresis (TTGE). RESULTS:
      Samples from both noninflamed and inflamed mucosa were obtained from 15 patients.
      The distribution of the bacterial populations was not different between
      noninflamed and inflamed mucosa. The Bacteroidetes phylum was dominant and
      accounted for 29% of MAB (0%-74%) in noninflamed tissues and 32% (0%-70%) in
      inflamed areas. The gamma Proteobacteria represented 12% (0%-70%) of MAB both in
      noninflamed and inflamed areas. The Clostridium coccoides group (Firmicutes
      phylum) represented 15% of MAB in noninflamed tissues versus 7% in inflamed
      areas. For most of the patients the similarity index between TTGE paired profiles
      was very high. CONCLUSION: The dominant MAB do not differ between noninflamed and
      inflamed ileal mucosa in Crohn's disease. This argues against a localized
      dysbiosis to explain the patchy distribution of mucosal lesions.

PMID- 17206671
TI  - Topical tacrolimus in the treatment of perianal Crohn's disease: exploratory
      randomized controlled trial.
AB  - BACKGROUND: The aim of this study is to evaluate the efficacy of topical
      tacrolimus in treating perianal Crohn's disease. METHODS: Nineteen patients,
      stratified into 7 with ulcerating, and 12 with fistulizing, perianal Crohn's
      disease were randomized to topical tacrolimus 1 mg/g (1 g ointment twice a day
      [bid]) or placebo for 12 weeks. Sixteen patients had been on, or were currently
      taking, azathioprine/6-MP, and 6 had received infliximab. The primary outcome in
      ulcerating disease was global improvement in perianal/anal lesions, as assessed
      by the attending physician; for fistulas, it was reduction of > or =50% of
      actively draining fistulas on 2 consecutive visits. Blood tacrolimus levels and
      adverse events were assessed. RESULTS: Three of 4 patients treated with topical
      tacrolimus for ulcerating disease improved compared with none of 3 in the placebo
      group. Complete healing was not achieved. In fistulizing disease, topical
      tacrolimus was not beneficial. Two tacrolimus-treated patients developed perianal
      abscesses, 1 after improvement in fistula drainage. Adverse events were otherwise
      infrequent and mild. Whole blood tacrolimus levels were detectable in only 2
      patients and were low. CONCLUSIONS: These preliminary data suggest that topical
      tacrolimus is effective and safe in the treatment of perianal or anal ulcerating
      Crohn's disease. This therapy is unlikely to be beneficial in fistulizing
      perianal Crohn's disease, although a larger study is required to confirm this.

PMID- 17206672
TI  - Linear growth improves during infliximab therapy in children with chronically
      active severe Crohn's disease.
AB  - BACKGROUND: The efficacy of infliximab as maintenance therapy in patients with
      otherwise chronically active Crohn's disease (CD) is well established. Data
      concerning the linear growth response are sparse and can only be accrued in
      children. METHODS: From September 2000 to February 2004, 32 children and
      adolescents (63% males; mean age 13.4 years, range 4.7-17.3) with chronically
      active CD despite immunomodulatory and prior corticosteroid therapy commenced
      infliximab therapy. Growth parameters standardized for age, gender, and pubertal
      development prior to and following infliximab therapy were compared. RESULTS: In
      all, 28 of 32 patients tolerated and responded to the induction regimen and 27
      responders continued to receive infliximab via regularly scheduled infusions (n =
      22) or episodically (n = 5) for a median of 26 months. Mean standard deviation
      score (SDS) for height at time of initiation of infliximab therapy was -1.15 +/-
      1.2 and had declined despite the use of other therapies from -0.44 +/- 1.1 at
      initial diagnosis. Increases in height velocity and stature during infliximab
      therapy were limited by pubertal stage: Tanner I-III: DeltaSDS for height
      velocity +3.94, for height +0.50, P < 0.001; Tanner IV, V: DeltaSDS for height
      velocity +0.22, for height 0.02, P = NS. CONCLUSIONS: Height velocity improves
      and height centile increases during infliximab therapy provided patients are
      treated prior to or in early puberty. These data support the use of infliximab in
      young patients with otherwise refractory disease, and suggest that ultimate
      height in this subset of children with severe CD may be less compromised than
      with previous therapies.

PMID- 17206673
TI  - Role of capsule endoscopy in inflammatory bowel disease: where we are and where
      we are going.
AB  - Capsule endoscopy (CE) is an innovative technological breakthrough that for the
      first time provides a noninvasive method to obtain high-resolution imaging of the
      entire small bowel. Since its recent inception, the diagnostic utility of CE has
      become well established for the evaluation of diverse ulcerative and inflammatory
      disorders of the jejunum and ileum. The incredible resolution of its lens (0.1
      mm) detects focal villous edema or atrophy, denuded, as well as ulcerated mucosal
      lesions missed by other imaging techniques. CE has been shown by meta-analysis to
      be a more sensitive method to investigate patients for small bowel Crohn's
      disease, with an incremental yield above 30% versus other imaging modalities. In
      patients with indeterminate colitis, CE is useful in distinguishing between
      ulcerative and Crohn's colitis. Among patients with established Crohn's disease,
      CE may be employed to determine: (1) the extent and severity of small bowel
      involvement, (2) postoperative recurrence, (3) post-therapy mucosal healing, and
      (4) whether active small bowel inflammatory lesions exist in the clinical setting
      of functional bowel disorder. Complications are rare and include capsule
      retention at stricture sites. The new patency capsule can diminish the risk of
      the latter problem in at-risk patients. CE can also serve as a guide to sites
      that require biopsies or dilatation by push or double-balloon enteroscopy.
      However, other causes of small bowel lesions may mimic Crohn's disease. A
      standard terminology system has thus been developed, and a CE Crohn's disease
      severity scoring index is currently undergoing validation studies.

PMID- 17206674
TI  - How adherent to treatment with azathioprine are patients with Crohn's disease in
      long-term remission?
AB  - BACKGROUND: Patients with longstanding quiescent Crohn's disease on azathioprine
      usually maintain an excellent quality of life but are also concerned about long
      term safety. This may affect adherence to treatment. The aim of the present study
      was to assess the adherence to azathioprine in a cohort of patients with Crohn's
      disease in long-term remission. METHODS: Thirty patients with Crohn's disease in
      remission on azathioprine for > or =48 months were enrolled in the study. All
      were asked to record the number of azathioprine tablets they consumed daily.
      Notes were kept every other month for 6 months. Adherence was defined as
      consumption of > or =80% of medication. RESULTS: Most patients (18/28, 74.3%)
      were not adherent to treatment. The mean (+/-SD) daily dose of azathioprine in
      adherent and nonadherent patients was 145 +/- 45 mg and 102 +/- 20 mg,
      respectively. However, there were no significant differences between the 2 groups
      in the mean IBDQ score and mean Crohn's Disease Activity Index (CDAI) score, both
      throughout the entire study and at each time point of the study. Male gender,
      single status, and consumption of >5 concomitant medications were associated with
      nonadherence. CONCLUSIONS: Most patients with Crohn's disease in longstanding
      remission had low self-reported adherence to azathioprine. Both male gender and
      single status were associated with nonadherence to azathioprine, whereas disease
      factors were not related to self-reported adherence. Patients considered
      nonadherent to treatment maintained disease remission and a quality of life
      similar to patients who were adherent to treatment.

PMID- 17206675
TI  - Comparative analysis of colonic gene expression of three experimental colitis
      models mimicking inflammatory bowel disease.
AB  - BACKGROUND: Mouse models of inflammatory bowel diseases (IBD) are used to unravel
      the pathophysiology of IBD and to study new treatment modalities, but their
      relationship to Crohn's disease (CD) or ulcerative colitis (UC) is speculative.
      METHODS: Using Agilent mouse TOX oligonucleotide microarrays, we analyzed colonic
      gene expression profiles in three widely used models of experimental colitis. In
      2 of the models (TNBS and DSS-induced colitis), exogenous agents induce the
      colitis. In the third model the colitis is induced after transfer of a T-cell
      population (CD4(+)CD45RB(high) T cells) that lacks regulatory cells into an
      immunodeficient host. RESULTS: Compared with control mice, in DSS, TNBS, and the
      CD45RB transfer colitis mice, 387, 21, and 582 genes were more than 2-fold
      upregulated in the intestinal mucosa. Analyses of exclusively shared gene
      expression profiles between the different models revealed that DSS/transfer
      colitis share 69 concordantly upregulated genes, DSS/TNBS 6, and TNBS/transfer
      colitis 1. Seven genes were upregulated in all three models. The CD45RB transfer
      model expression profile included the most genes that are known to be upregulated
      in IBD. Of 32 genes that are known to change transcriptional activity in IBD
      (TNF, IFN-gamma, Ltbeta, IL-6, IL-16, IL-18R1, IL-22, CCR2, 7, CCL2, 3, 4, 5, 7,
      11, 17, 20, CXCR3, CXCL1, 5, 10, Mmp3, 7,9, 14, Timp1, Reg3gamma, and Pap, S
      100a8, S-100a9, Abcb1, and Ptgs2), 2/32 are upregulated in TNBS, 15/32 are
      upregulated or downregulated in DSS and 30/32 are upregulated or downregulated in
      the CD45RB transfer colitis. CONCLUSION: The pattern of gene expression in the
      CD45RB transfer model most closely reflects altered gene expression in IBD.

PMID- 17206676
TI  - Active and passive smoking in childhood is related to the development of
      inflammatory bowel disease.
AB  - BACKGROUND: The highest prevalence of smoking in the United States is in
      Kentucky, where smoking typically begins in childhood. The state has many
      patients who suffer from inflammatory bowel diseases (IBD). The primary aim of
      this study was to assess whether exposure to active and/or passive tobacco smoke
      in childhood is related to the likelihood of developing IBD. METHODS: Recruited
      into this prospective study were a total of 672 participants (253 patients with
      Crohn's disease [CD], 177 patients with ulcerative colitis [UC], and 242
      controls), all of whom were asked to complete the Behavioral Risk Factor
      Surveillance Survey modified by the addition of 4 questions on childhood passive
      smoke exposure. RESULTS: Survey response rate was 84%. CD and UC patients were
      more likely than controls to begin smoking regularly by ages 10 and 15,
      respectively, suggesting that becoming a regular smoker at a younger age may be
      associated with a subsequent diagnosis of IBD. Smoking by age 10 was associated
      with an earlier age at diagnosis with UC, but not with CD. CD patients were more
      likely than controls to have prenatal smoke exposure (odds ratio [OR], 1.72; 95%
      confidence interval [CI], 1.1-2.71) and were more likely to have passive smoke
      exposure during childhood, with 1 or both parents or other household members
      being smokers (OR, 2.04; 95% CI, 1.28-3.31). CONCLUSIONS: Passive and active
      smoke exposure in childhood influences the development of IBD. A high incidence
      of this disease in a state with a high rate of cigarette smoking underscores the
      profound role of environmental factors in the etiology of these illnesses.

PMID- 17206677
TI  - Long-standing colonic inflammation is associated with a low prevalence of
      diverticuli in inflammatory bowel disease patients.
AB  - BACKGROUND: Diverticulosis is associated with high intracolonic pressure and a
      weakened bowel wall. Chronic colitis is characterized by liquid stools suggestive
      of low intracolonic pressure and a thickened bowel wall. Therefore, the aim of
      this study was to assess the prevalence of diverticulosis in colitis patients.
      METHODS: Colonoscopy results of patients with inflammatory bowel disease (IBD)
      associated colitis older than 50 years were retrospectively evaluated and
      compared with those of patients who underwent screening colonoscopy. Only
      patients with biopsy-proven disease, disease duration of more than 5 years, and
      disease beyond the distal 20 cm were included. RESULTS: In all, 1037 patients
      were diagnosed by colonoscopy as suffering from IBD-associated colitis between
      1987-2005. After exclusion of patients who did not meet the inclusion criteria
      the study population consisted of 314 IBD patients and 1023 age-matched control
      patients. A significantly higher percent of diverticuli was detected in the
      control group compared with the IBD group (15% versus 3.5%, P < 0.001). No
      significant difference in the prevalence of diverticuli was detected between the
      three subtypes of IBD patients (2% in ulcerative colitis versus 4.7% in Crohn's
      colitis versus 7.6% in indeterminant colitis). Neither disease duration nor the
      specific colonic segment involved had a significant influence on the prevalence
      of diverticulosis. CONCLUSIONS: Long-standing colonic inflammation in IBD
      patients is associated with a lower prevalence of diverticuli.

PMID- 17206678
TI  - Genetic risk factors in patients with inflammatory bowel disease and vascular
      complications: case-control study.
AB  - BACKGROUND: Inherited risk factors have been suggested to play an important role
      in the pathogenesis of vascular complications of inflammatory bowel disease
      (IBD). The aim of the present study was to investigate the role of mutations
      associated with cardiovascular disease in IBD patients with or without vascular
      complications compared with thrombotic and healthy controls (HC). METHODS: Twelve
      polymorphisms of thrombophilic and vasoactive genes were evaluated in a group of
      30 IBD patients with vascular complications (IBD-VC) compared with 60 IBD
      patients without vascular complications, 30 thrombotic controls (TC), and 54
      healthy controls, using a commercially available kit. RESULTS: No significant
      differences between IBD-VC and TC concerning the carriage of these mutations were
      found. The frequencies of the factor V (FV) 506 RQ (Leiden) genotype and the 506Q
      allele were significantly higher in these groups than in HC (P < 0.05) but not
      IBD controls (P > 0.05). The allele frequency of the mutant 4G allele of the
      plasminogen activator inhibitor (PAI) polymorphism, similar in the IBD-VC and TC
      groups, was significantly higher in these groups compared with the IBD group (P =
      0.03) and the HC (P = 0.001). It is noteworthy that there was a trend of
      association of FV R506Q polymorphism with venous thrombosis and PAI-1 gene
      polymorphism with arterial thrombosis. CONCLUSIONS: Our results suggest that the
      investigated gene polymorphisms do not differ in patients with IBD-VC and TC. FV
      R506Q and PAI-1 gene polymorphisms might be associated with the increased risk of
      development of vascular complications in IBD.

PMID- 17206679
TI  - Effect of the anti-tumor necrosis factor-alpha antibody infliximab on the ex vivo
      mucosal matrix metalloproteinase-proteolytic phenotype in inflammatory bowel
      disease.
AB  - BACKGROUND: Previous studies have shown an upregulation of matrix
      metalloproteinases (MMPs) in intestinal tissue of patients with inflammatory
      bowel disease (IBD) and significant clinical improvement after administration of
      the anti-TNF-a antibody infliximab. The aims of our study were to determine
      expression and secretion of MMP-1, -2, -3, -9, and their inhibitors TIMP-1, -2 by
      IBD versus control intestinal mucosa ex vivo and to assess the regulatory
      capacity by infliximab of the proteolytic phenotype. METHODS: Intestinal mucosal
      explants from 20 IBD and 15 control patients were cultured with or without
      infliximab and/or the T-cell activator pokeweed mitogen (PWM). Explants and
      culture supernatants were analyzed for MMPs, TIMPs, and TNF-alpha protein,
      activity and/or mRNA levels. All patients were genotyped for functional TNF
      alpha, MMP, and TIMP single nucleotide polymorphism (SNP) loci. RESULTS:
      Expression of MMP and TIMP protein/activity in basal medium was higher in IBD
      versus control explants. Dependent on genotype at SNP loci, infliximab
      downregulated MMP-1, -3, and -9 relative to TIMP-1 and -2 and also decreased MMP
      1 and -3 activities, while PWM enhanced these levels, partly counteracted again
      by infliximab. The expression of MMP-2 relative to TIMP did not change by
      treatment with infliximab and/or PWM. CONCLUSIONS: The high expression of MMPs in
      patients with IBD suggests a role for these proteinases in the pathogenesis of
      this disease. Infliximab seems to induce a genotype-associated matrix protective
      phenotype, which may contribute to the observed therapeutic efficacy of this drug
      in IBD, particularly at the mucosal surface.

PMID- 17206680
TI  - Antibodies against cyclic citrullinated peptide (CCP) in inflammatory bowel
      disease patients with or without arthritic manifestations.

PMID- 17206681
TI  - Potential role for the common cystic fibrosis DeltaF508 mutation in Crohn's
      disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is an epithelial barrier disease
      that is thought to result from a dysregulated interaction with bacteria in the
      intestine of genetically predisposed individuals. The cystic fibrosis
      transmembrane conductance regulator (CFTR), which is mutated in the autosomal
      recessive disease cystic fibrosis, modulates gut permeability, mucus production,
      and epithelial interactions with bacteria. The cystic fibrosis DeltaF508 mutation
      is commonly found in the general population and has been shown to result in a
      reduced number of CFTR molecules at the surface of epithelial cells. Given the
      important biological functions of CFTR in the intestine, we tested whether this
      mutation is of relevance to IBD. METHODS: Using DNA heteroduplex analysis, we
      investigated the distribution of DeltaF508 heterozygosity in 2568 subjects from
      three independent cohorts of Italian, Swedish, and Scottish IBD patients and
      controls. RESULTS: In all three cohorts an association between DeltaF508 and
      Crohn's disease (CD) was observed. Specifically, DeltaF508 heterozygosity was
      markedly underrepresented in CD patients from Italy and Sweden (P = 0.021 and
      0.027 versus controls, respectively), while stratification for disease location
      revealed an absence of DeltaF508 carriers among Scottish CD patients with right
      sided colitis (P = 0.023 versus all other locations). CONCLUSIONS: DeltaF508
      heterozygosity might exert a protective effect in CD.

PMID- 17206682
TI  - NOD2/CARD15 disease associations other than Crohn's disease.
AB  - At this moment, few confirmed associations between NOD2 mutations and diseases
      other than Crohn's disease (CD) and Blau syndrome (BS) have been reported, but
      research is ongoing in several fields where a genetic susceptibility factor
      and/or a role for the innate immune system is suspected. Whether the Crohn's
      associated CARD15 mutations lead to a loss or gain of function of the NOD2
      receptor is subject to controversy, and by which mechanisms this change in
      function might increase the susceptibility to CD is still under investigation.
      The possible involvement of NOD2/CARD15 in the pathogenesis of certain diseases
      with already (partially) unraveled pathophysiologic mechanisms might contribute
      to our further understanding of NOD2/CARD15 and its function in CD. We review
      studies on the association of CARD15 variants with diseases other than CD. The
      association of NOD2/CARD15 mutations with CD and BS, and possibly also early
      onset sarcoidosis, suggests a role for the gene in the development of granulomata
      and granulomatous diseases, possibly by inappropriate activation of the immune
      system. The data from the oncology field suggest that this inappropriate
      activation might even lead to uncontrolled proliferation of certain cell types.
      The studies in allergic diseases and atopy are the largest so far, and the
      association of NOD2/CARDI5 mutations with atopic phenotypes might be an
      indication that CARD15 also plays a role in the Th2 pathway. Finally,
      transplantation studies indicate that the genetic background of a patient should
      be taken into account when considering hematopoietic stem cell transplantation,
      given the increased risk of mortality and graft versus host disease observed.
      Whether NOD2 variants are also associated with an increased risk for infections
      and sepsis in patients receiving immunosuppressive therapies is unclear.

PMID- 17206683
TI  - Non-enteric salmonella spontaneous peritonitis--a new complication of an old
      immunosuppressant?

PMID- 17206684
TI  - A new type of strictureplasty for the treatment of multiple long stenosis in
      Crohn's disease.

PMID- 17206685
TI  - Blockade of colony stimulating factor-1 (CSF-I) leads to inhibition of DSS
      induced colitis.
AB  - BACKGROUND: Intestinal inflammation associated with inflammatory bowel disease
      (IBD) is typically characterized by an inflammatory cell infiltrate and pro
      inflammatory cytokine production. Of particular interest, the frequency of colony
      stimulating factor-1 (CSF-l)-expressing cells is increased in active lesions. In
      this study, we have investigated the role of CSF-1 in mucosal inflammation, using
      a murine model of colitis induced by dextran sulfate sodium (DSS). METHODS: A
      neutralizing anti-CSF-1 antibody was administered to Balb/c mice that received
      DSS in their drinking water. Signs of colitis, such as clinical disease score,
      cellular infiltrate, and cytokine production, were assessed. RESULTS:
      Administration of a neutralizing anti-CSF-1 antibody significantly inhibited DSS
      induced colitis. Clinical symptoms, such as weight loss and the appearance of
      diarrhea or fecal blood, were reduced by CSF-1 blockade; histologic scores were
      also improved. The cellular infiltrate of macrophages and T cells was inhibited
      and a trend toward reduced production of pro-inflammatory cytokines was noted.
      CONCLUSIONS: This is the first study to demonstrate that CSF-1 plays an important
      role in mediating intestinal mucosal inflammation and therefore may prove to be
      an attractive therapeutic target for intestinal diseases such as inflammatory
      bowel disease.

PMID- 17206686
TI  - Inflammation is the main determinant of low bone mineral density in pediatric
      inflammatory bowel disease.
AB  - AIMS: To assess bone mineral density (BMD) in children with Crohn's disease (CD)
      and ulcerative colitis (UC) and to investigate the role of inflammation and
      steroids on BMD. METHODS: Lumbar spine areal BMD was measured by DXA, and
      volumetric BMD was then estimated (BMAD); inflammatory cytokines (TNF-alpha, IL
      6, IL-10, and IL-12) were dosed in peripheral blood; and cumulative and daily
      doses of steroids were calculated. Therapy with infliximab (IFX) was considered
      for CD patients. RESULTS: Fifty-six patients with IBD (35 CD, 21 UC) were
      studied. An inverse correlation was found between BMAD and IL-6 in patients with
      UC (r = -0.65); no correlation was found between BMAD and serum levels of TNF
      alpha, IL-10, and IL-12 in all patients. Disease activity indexes use inversely
      correlated with BMAD (r = -0.62 in patients with CD and r = -0.64 in patients
      with UC). Cumulative dose of corticosteroids and duration of therapy did not
      correlate with BMAD. The 10 patients with CD who were treated with IFX had higher
      BMAD (-1 +/- 0.8) than those never treated with IFX (-1.8 +/- 0.8). Mean
      Pediatric Crohn's Disease Activity Index and body mass index in patients with CD
      (R(2) = 0.48) and IL-6 level in patients with UC (R(2) = 0.43) were found to be
      independent and significant predictors of BMAD. CONCLUSIONS: In children with
      IBD, inflammation is an important determinant of bone loss, as shown by the
      correlation of BMAD with serum IL-6 and with disease activity indexes as well as
      by the beneficial effect of IFX on bone density. Corticosteroids seem to be a
      less important variable in pediatric IBD-related BMD reduction than previously
      believed.

PMID- 17206687
TI  - Occult hepatitis B and infliximab-induced HBV reactivation.

PMID- 17206688
TI  - Antibodies to saccharomyces cerevisiae in Crohn's disease: higher titers are
      associated with a greater frequency of mutant NOD2/CARD15 alleles and with a
      higher probability of complicated disease.
AB  - BACKGROUND: Both antibodies to Saccharomyces cerevisiae (ASCA) and carriage of
      two mutated NOD2/CARD15 alleles are associated with ileal Crohn's disease (CD)
      and complications requiring bowel surgery. We assessed the ASCA titer as a marker
      of CD clinical behavior. METHODS: In a cross-sectional study, we phenotyped 117
      unrelated CD patients. Titers (Units, U) of ASCA IgG and IgA were measured and
      patients were genotyped for three high-risk NOD2/CARD15 alleles. Multiple
      logistic regression and Cox regression analyses were used to assess the
      association of factors to CD phenotype and time to surgery. RESULTS: ASCA
      seropositivity was associated with younger age at diagnosis, ileal disease, and
      complicated (stricturing or penetrating) behavior. There was a dose-response
      between the number of mutant NOD2/CARD15 alleles and the prevalence and titers of
      ASCA. The ASCA titer and tobacco use were associated with ileal disease
      independently of NOD2/CARD15 status. The ASCA titer (odds ratio (OR): 2.7 per 25
      U, 95% confidence interval (CI): 1.5-46.7) and ileal disease were associated with
      stricturing/penetrating behavior, independently of NOD2/CARD15 status. Patients
      with ileal CD and ASCA titers of 41 U and 60 U needed 10 and 5 years of disease,
      respectively, to accumulate a 50% risk of complications. CONCLUSIONS: ASCA+
      patients had a greater frequency of mutant NOD2/CARD15 alleles. Nonetheless,
      higher ASCA titers were associated with higher probabilities of ileal CD and
      stricturing/penetrating behavior independently of NOD2/CARD15 status. Higher ASCA
      titers were associated with more rapid development of complications. This
      quantitative marker may prove useful in risk-stratifying patients to more
      aggressive antiinflammatory therapies.

PMID- 17206689
TI  - Efflux transporters in ulcerative colitis: decreased expression of BCRP (ABCG2)
      and Pgp (ABCB1).
AB  - BACKGROUND: Efflux transport proteins are important components of the intestinal
      barrier against bacterial toxins, carcinogens, and drugs. This investigation was
      conducted to determine the expression of Breast Cancer Resistance Protein
      (BCRP/ABCG2), P-glycoprotein (Pgp/MDR1/ABCB1), and Multidrug Resistance Protein 2
      (MRP2/ABCC2) in the gut mucosa of patients with ulcerative colitis (UC). METHODS:
      Patients were thoroughly diagnosed according to well-established clinical,
      endoscopic, and histologic criteria to be included in the group of patients with
      active UC (n = 16) or UC in remission (n = 17). Colonic and rectal mucosa from
      patients with UC were compared with tissues from control subjects (n = 15). The
      mRNA expression (TaqMan) of the efflux transporters and the proinflammatory
      cytokines interleukin (IL)-1beta and IL-6 was determined. Western blot was used
      in the analysis of protein expression and the tissue localization of BCRP was
      determined with confocal microscopy. RESULTS: BCRP and Pgp expression was
      strongly reduced in individuals with active inflammation compared with controls
      and was negatively correlated with the levels of IL-6 mRNA. The BCRP staining of
      colonic epithelium seen in healthy mucosa was diminished in inflamed tissues,
      with concurrent disruption of epithelial F-actin structure. CONCLUSIONS: Two of
      the efflux transporters of importance for the barrier function of the gut mucosa,
      Pgp and BCRP, are expressed at strongly reduced levels during active inflammation
      in patients with UC. Investigations are warranted to determine whether the low
      levels of efflux transporters during active UC contribute to altered transport
      and tissue exposure of carcinogens, bacterial toxins, and drugs.

PMID- 17206690
TI  - Voluntary childlessness is increased in women with inflammatory bowel disease.
AB  - BACKGROUND: The women's health aspect of inflammatory bowel disease (IBD) is a
      newer area of study; childbearing issues have received little attention despite
      the fact that IBD affects women predominantly during their childbearing years.
      The aim of this study was to better understand patients' considerations about
      pregnancy-related issues and to examine trends in childbearing so that physicians
      are able to better tailor their advice to IBD-specific concerns. METHODS: Data
      were gathered from specific questions in 3147 surveys mailed anonymously to all
      members of the Crohn's and Colitis Foundation of America (CCFA) Illinois Carol
      Fisher chapter. The subjects were provided a pre-addressed, pre-stamped return
      envelope and were instructed to return their completed surveys with no
      identifying information. Subjects were from the Illinois community. Females IBD
      patients were 15-44 of age and were members of the CCFA Illinois Carol Fisher
      chapter. RESULTS: In this study, 169 females age 15-44 years with IBD, 110 with
      Crohn's disease (CD) and 59 with ulcerative colitis (UC), were identified. Most
      subjects were white. IBD patients had a higher rate of voluntary childlessness
      (CD 18%, UC 14%) than the 6.2% seen in the general population (P = 0.001 for CD,
      P = 0.08 for UC). Women with UC had a lower rate of temporary childlessness (CD
      28%, UC 13.6%) than the general population (33%) (P = NS and P < 0.0001 for UC).
      The rates of nonvoluntary childlessness in IBD were similar to the general
      population. Women with IBD also had fewer children than their state and national
      counterparts. The state of the patients' IBD, including those who had gone
      through a previous pregnancy with IBD, did not alter their resolve to have
      children. The educational level of our subjects was higher than the nationwide
      and statewide levels; 76% of the subjects used contraception before diagnosis of
      IBD, and 82% used it after diagnosis. The most common choices were oral
      contraception, barrier methods, and abstinence. This study was unable to compare
      the lifetime rates of complications of pregnancy with population-based controls
      because such data were unavailable. Furthermore, their findings in this study may
      not be generalized to all ethnic groups because our population was mostly white.
      CONCLUSIONS: Women with IBD had a higher rate of voluntary childlessness and
      fewer children than the general population. These observations are likely
      attributable to a higher educational achievement and to racial background of the
      patients rather than to IBD-related reasons. Although contraception use in
      patients with IBD was lower that in the general population, use was higher after
      the diagnosis of IBD than before the diagnosis. Contraceptive choices and
      adoption rates were similar to the general population. Women with CD were more
      affected by miscarriages after diagnosis with IBD than those with UC.

PMID- 17206691
TI  - Health-related quality of life after ileocolonic resection for Crohn's disease:
      long-term results.
AB  - BACKGROUND: Crohn's disease (CD) is a chronic illness that interferes with the
      daily life of those affected. The aim of the present study was to evaluate long
      term health-related quality of life (HRQL) outcome and its clinical predictors in
      CD patients who have had ileocolonic resection. METHODS: Ninety-seven CD
      patients, with a mean follow-up of 47.1 months (95% CI, 40.7-53.5 months) after
      ileocolonic resection, were interviewed by telephone and responded to the generic
      Cleveland Global Quality of Life (CGQL) questionnaire, and 63 of them also agreed
      to come to our outpatient clinic to have a Crohn's Disease Activity Index (CDAI)
      assessment and blood test and to answer the disease-specific Padova Inflammatory
      Bowel Diseases Quality of Life (PIBDQL) questionnaire. Control groups also were
      enrolled. RESULTS: The CGQL scores of the 97 CD patients were similar to those of
      69 healthy controls. Only the item on current quality of health was scored
      significantly lower by patients with CD. In contrast, the PIBDQL item and total
      scores of the CD patients were all significantly lower than those of the
      respective healthy controls (P < 0.05). Multivariate analysis showed that the
      CGQL and PIBDQL scores both had a strong linear relationship with number of daily
      stools and with CDAI score (P < 0.05). CONCLUSIONS: Despite CD patients who have
      undergone ileocolonic resection having an apparently normal quality of life with
      a good energy level, as shown by the CGQL, their long-term HRQL is still affected
      by a significantly impaired quality of health. In fact, the PIBDQL questionnaire
      showed significant impairment of bowel and systemic symptom domains with
      important consequences for emotional and social functions. HRQL seems to be
      significantly related only to current disease activity.

PMID- 17206692
TI  - Apolipoprotein A-IV is an independent predictor of disease activity in patients
      with inflammatory bowel disease.
AB  - BACKGROUND: ApoA-IV, an apolipoprotein (apo) with antioxidant, antiatherogenic,
      and antiinflammatory properties, was recently demonstrated to inhibit dextran
      sulfate sodium (DSS)-induced experimental colitis in mice. We therefore
      hypothesized that apoA-IV may be associated with disease activity in patients
      with inflammatory bowel disease (IBD). METHODS: We addressed this question by
      testing for associations between apoA-IV genotypes, apoA-IV plasma levels,
      inflammatory parameters, and clinical disease activity in 206 patients with
      Crohn's disease (CD), 95 subjects with ulcerative colitis (UC), and 157 healthy
      controls. RESULTS: In CD patients, apoA-IV plasma levels were inversely
      associated with C-reactive protein (CRP) (P = 0.005) and disease activity (P =
      0.01) in univariate analysis. In multiple logistic regression analysis, apoA-IV
      levels were identified as an independent predictor of elevated CRP (odds ratio
      [OR] 0.956, 95% confidence interval [CI]: 0.916-0.998, P = 0.04) and active
      disease (OR 0.957, 95% CI: 0.918-0.998, P = 0.04). In UC patients the apoA-IV
      gene variant 360 His (P = 0.03) but not apoA-IV levels (P = 0.15) were associated
      with increased disease activity in univariate analysis. This association,
      however, was lost in multiple logistic regression analysis (OR 3.435, 95% CI
      0.995-11.853, P = 0.05). CONCLUSIONS: To our knowledge, this is the first study
      to demonstrate an association of apoA-IV with disease activity in patients with
      CD. Further studies are needed to define the relationship of apoA-IV to IBD.

PMID- 17206693
TI  - Quality-of-life measurement in patients with inflammatory bowel disease receiving
      social support.
AB  - BACKGROUND: Crohn's disease and ulcerative colitis, referred to as inflammatory
      bowel diseases, affect mainly young adults and have an elevated morbidity and a
      negative effect on quality of life. This study aimed to compare the health
      related quality of life between 2 randomized groups of patients with inflammatory
      bowel disease: (1) the supported group (SG), patients receiving social support
      for an 18-month period, and (2) the control group (CG), patients receiving no
      social support. METHODS: Health-related quality of life was assessed at 4 moments
      with the Portuguese versions of the Medical Outcomes Study Short Form 36 and the
      Inflammatory Bowel Disease Questionnaire (IBDQ), both validated in Brazil.
      RESULTS: In the SG, using analysis of variance for repeated measures complemented
      by the Bonferroni test positive variations were observed (1) in the Social
      Aspects domain, between the first and third evaluations (P = 0.044), and (2) in
      the Emotional Aspects domain, between the first and second and the third and
      fourth evaluations (P = 0.029). CONCLUSIONS: In the sample studied, social
      support, measured by use of the Inflammatory Bowel Disease Questionnaire, had a
      positive impact on the social and emotional aspects of quality of life.

PMID- 17206694
TI  - Medium-term results of oral tacrolimus treatment in refractory inflammatory bowel
      disease.
AB  - BACKGROUND: This study aimed to evaluate the efficacy of oral tacrolimus in
      patients with inflammatory bowel disease (IBD) refractory to conventional
      therapy, including azathioprine, 6-mercaptopurine, and infliximab. METHODS:
      Retrospective review of all patients with IBD treated with oral tacrolimus was
      undertaken. Tacrolimus was administered t an initial dose of 0.05 mg/kg twice
      daily, aiming for serum trough levels of 5-10 ng/mL. We evaluated clinical
      response, a retrospective estimated Crohn's disease activity index (CDAI) for
      Crohn's disease (CD), modified Truelove-Witts index for ulcerative colitis (UC),
      and modified pouch disease activity index (mPDAI) for pouchitis. Patients had
      been monitored clinically for benefit and side effects and by whole blood
      tacrolimus level approximately every 4 weeks for the duration of treatment.
      Clinical remission was defined as an estimated CDAI <150 (CD), an inactive
      disease score on the Truelove-Witts index (UC), and mPDAI <5 (pouchitis).
      RESULTS: Twelve patients with CD, six with UC, and one with pouchitis, all
      resistant to previous therapies, were treated for a median of 5 months. After 4
      weeks 10 CD (83%), four UC (67%) patients, and one pouchitis patient had a
      clinical response. There was a median reduction of the estimated CDAI of 108
      points (range 35-203; P = 0.002) and stool frequency of three per day at week 4.
      Remission was achieved in 42% (5/12) of CD and 50% (3/6) of UC patients at the
      end of follow-up. Side effects included temporary elevated creatinine (n = 1),
      tremor (n = 3), arthralgia (n = 1), insomnia (n = 1), and malaise (n = 1). Four
      patients discontinued treatment due to side effects. CONCLUSION-: Oral tacrolimus
      is well tolerated and effective in patients with refractory IBD in the short- to
      medium-term. Further controlled, long-term evaluation is warranted.

PMID- 17206695
TI  - 5-Aminosalicylic acid therapy and the risk of colorectal cancer among patients
      with inflammatory bowel disease.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) affecting the colon
      are at increased risk of developing colorectal cancer (CRC). Published data are
      conflicting about whether 5-aminosalicylic acid (5-ASA) has chemopreventive
      properties against IBD-related carcinogenesis. The objective of this
      observational study was to determine if an association between 5-ASA therapy and
      CRC risk exists in IBD patients. METHODS: Adult patients with a new CRC diagnosis
      (n = 18,440) were identified from 2 large administrative claims databases. For
      each case, 20 control patients with no record of CRC diagnosis or bowel surgery
      (n = 368,800) were identified. RESULTS: An IBD diagnosis was associated with a 6-
      to 7-fold increased risk of CRC (ulcerative colitis, crude odds ratio [OR] =
      6.72, 95% CI, 5.79-7.81; Crohn's disease, crude OR = 6.60, 95% CI, 5.56-7.82).
      Among patients with IBD (364 CRC cases, 1172 controls), exposure to 5-ASA therapy
      of any dose or duration during the 12 months before CRC diagnosis was not
      associated with a reduced risk of CRC (OR = 0.97; 95% CI, 0.77-1.23). However,
      there was a trend toward a decreased risk of CRC with increasing number of
      mesalamine prescriptions in the previous year, though statistical significance
      was not achieved (trend P = 0.08). CONCLUSIONS: Treating IBD patients with 5-ASA
      medications was not found to have a protective effect against colitis-related CRC
      when assessed over a short period of exposure.

PMID- 17206696
TI  - Multicenter randomized-controlled clinical trial of probiotics (Lactobacillus
      johnsonii, LA1) on early endoscopic recurrence of Crohn's disease after lleo
      caecal resection.
AB  - BACKGROUND: Seventy percent of Crohn's disease (CD) patients exhibit anastomotic
      recurrence within 1 year after ileo-caecal surgery. Recent clinical trials
      suggest the beneficial use of probiotics in the control of intestinal
      inflammation in pouchitis and ulcerative colitis. This study is a multicenter
      clinical trial evaluating the efficacy of an oral administration of the probiotic
      LAl on early post-operative endoscopic recurrence of CD. METHODS: Seventy
      patients with CD were enrolled prior to elective ileo-caecal resection and
      randomly assigned after surgery to daily treatment with either Lactobacillus
      johnsonii, LA1, Nestle (1010 colony-forming units, CFU) (group A, n = 34) or
      placebo (group B, n = 36) for 12 weeks. The primary objective was to assess the
      effect of LAl on the endoscopic recurrence rate at 12 weeks. Stratification was
      performed according to smoking status at randomization. RESULTS: Seven and 14
      patients were excluded in the LA1 and placebo groups, respectively. In intention
      to-treat analysis, the mean endoscopic score was not significantly different
      between the two treatment groups at 3 months (LA1 versus placebo: 1.50 +/- 1.32
      versus 1.22+/-1.37, treatment effect: P = 0.48, smoke effect: P = 0.72). The
      percentage of patients with severe recurrence (i3 + i4) was 21% and 15% in the
      LAl and placebo groups, respectively (P = 0.33). Using a per-protocol (PP)
      analysis, the mean endoscopic score was not significantly different between the
      two treatment groups (LAl versus placebo groups: 1.44 +/-1.31 versus 1.05 +/-
      1.21, P = 0.32). The percentage of patients with severe recurrence (i3 + i4) was
      19% and 9% in the LAl and placebo groups, respectively (P = 0.054). Clinical
      relapse rate (CDAI [CD activity index] > 150, with an increase of CDAI > 70
      points or greater from baseline) in the LAl and placebo groups was 15% (4/27) and
      13.5% (3/22), respectively (PP analysis: chi-square test, P = 0.91 and log-rank
      test: P = 0.79). CONCLUSION: Oral administration of the probiotic LA1 in patients
      with CD failed to prevent early endoscopic recurrence at 12 weeks after ileo
      caecal resection.

PMID- 17206697
TI  - Value of wireless capsule endoscopy in patients with indeterminate colitis
      (inflammatory bowel disease type unclassified).
AB  - BACKGROUND: Wireless capsule endoscopy (WCE) can identify small bowel mucosal
      lesions not seen with other imaging modalities. This technique can therefore play
      an important diagnostic role in the evaluation of patients with inflammatory
      bowel disease type unclassified (IBDU). We report on a multicentric study whose
      objective was to evaluate the value of WCE to increase diagnostic accuracy in
      categorizing IBDU. METHODS: Thirty patients with IBDU and negative serology were
      included. WCE was performed with a standard Pillcam capsule. Outcome measures
      were classified as suggestive of Crohn's disease (CD) when -3 ulcerations were
      present. RESULTS: WCE displayed endoscopic features suggestive for CD in 5
      patients. In 6 other patients, WCE was negative, but repeated ileocolonoscopy
      with biopsies performed during follow-up evaluation revealed CD in 5 and
      ulcerative colitis (UC) in 1 patient. UC was found in a seventh case at colectomy
      performed just after WCE. Eighteen patients remained with a diagnosis of IBDU 16
      months on average after WCE. CONCLUSIONS: WCE is a potentially clinically useful
      technique for categorizing a subgroup of patients with IBDU, although negative
      WCE does not exclude further diagnosis of CD. Patients with negative WCE who
      remain IBDU at follow-up evaluation may belong to an original subgroup of IBD.

PMID- 17206698
TI  - Group-based intervention program in inflammatory bowel disease patients: effects
      on quality of life.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and
      Crohn's disease (CD) have great impact on patients' health-related quality of
      life (HRQOL). The aim of this study was to develop an integrated medical and
      psychological/ psychosocial group-based intervention program for IBD patients and
      to evaluate if such a program could influence the patients' HRQOL and coping
      abilities. METHODS: IBD patients in remission or with low disease activity were
      randomized to intervention or control groups. The intervention comprised nine
      weekly sessions, alternating lectures, and group therapy sessions. The
      Inflammatory Bowel Disease Questionnaire (IBDQ) and the Sense of Coherence scale
      (SOC) were used to measure HRQOL and coping ability at 0, 6, and 12 months. The
      intervention was evaluated by a visual analog scale (VAS) and written comments by
      a content analysis. RESULTS: In all, 24 patients were included in the
      intervention group and 20 in the control group. The mean IBDQ score showed no
      statistically significant differences before (173.9) or after the intervention at
      month 6 (175.7) or at month 12 (171.8), or when comparing intervention and
      controls at month 12. Similarly, there were no statistically significant
      differences in mean SOC before or after intervention or when comparing groups.
      The VAS and the content analysis showed that the intervention was well
      appreciated by the patients. CONCLUSIONS: The group-based intervention program
      was feasible and highly appreciated. There were no statistically significant
      differences in average IBDQ or SOC over time or in comparison with controls,
      although a significant increase was seen in patients with short disease duration.

PMID- 17206699
TI  - Symptomatic overlap between irritable bowel syndrome and microscopic colitis.
AB  - BACKGROUND: Microscopic colitis is diagnosed on the basis of histologic criteria,
      and irritable bowel syndrome (IBS) is diagnosed by symptom-based criteria. There
      has been little investigation into the symptomatic overlap between these
      conditions. Our aim was to assess the prevalence of symptoms of irritable bowel
      syndrome in a population-based cohort of patients with microscopic colitis.
      METHODS: The Rochester Epidemiology Project (REP), a medical records linkage
      system providing all health care data for the defined population of Olmsted
      County, Minnesota, was used to identify all county residents with a diagnosis of
      microscopic colitis between 1985 and 2001. The medical records of these
      individuals were reviewed to ascertain symptoms consistent with Rome, Rome II,
      and Manning criteria for irritable bowel syndrome. RESULTS: One hundred thirty
      one cases of microscopic colitis were identified. Median age at diagnosis was 68
      years (range, 24-95); 71% were women. Sixty-nine (53%) and 73 (56%) met Rome and
      Rome II criteria for irritable bowel syndrome, respectively. Fifty-four (41%) had
      three or more Manning criteria. Forty-three (33%) had previously been diagnosed
      with irritable bowel syndrome. CONCLUSIONS: In this population-based cohort of
      histologically confirmed microscopic colitis, approximately one-half met symptom
      based criteria for the diagnosis of irritable bowel syndrome. The clinical
      symptom-based criteria for irritable bowel syndrome are not specific enough to
      rule out the diagnosis of microscopic colitis. Therefore, patients with suspected
      diarrhea-predominant irritable bowel syndrome should undergo biopsies of the
      colon to investigate for possible microscopic colitis if symptoms are not well
      controlled by antidiarrheal therapy.

PMID- 17206700
TI  - Fecal excretion of deoxyribonucleic acid in long-term follow-up of patients with
      inactive ulcerative colitis.
AB  - BACKGROUND: We have developed a technique for measuring fecal excretion of human
      DNA by assuming that luminal desquamation of epithelial and inflammatory cells
      increases in damaged colonic mucosa. However, the clinical usefulness of this
      technique in the follow-up of patients with ulcerative colitis has not been
      established. The aim of this study was to determine the stability of fecal DNA in
      inactive ulcerative colitis and its potential value as an indicator of relapse.
      METHODS: The 54 patients with clinically quiescent ulcerative colitis in this
      prospective study were followed for 12 months or until clinical relapse (clinical
      activity index > 7). Fecal calprotectin concentration was determined by ELISA,
      and fecal DNA concentration was determined by quantitative PCR. RESULTS: During
      the year of follow-up, 23 of the 54 patients relapsed, with a median increase in
      the colitis activity index from 1.0 to 8.0 (P < 0.01). Median fecal DNA remained
      unchanged in patients with stable, inactive colitis, ranging from 6.8
      copies/microg at inclusion to 1.7 copies/microg at the end of follow-up. Fecal
      calprotectin level also was unchanged, ranging from 414.0 microg/g at inclusion
      to 128.9 microg/g at the end of follow-up. In contrast, fecal DNA concentration
      increased significantly in patients who relapsed (259.0 versus 3.9 copies/microg
      at entry; P < 0.01). Similar increases in relapsing patients were also observed
      with fecal calprotectin. ROC curve analysis to assess the accuracy of fecal DNA
      and calprotectin in detecting relapses during follow-up yielded similar results.
      CONCLUSIONS: Fecal DNA concentration remained stable in patients with inactive
      ulcerative colitis but increased significantly with relapses. Determining fecal
      DNA concentration may be a new objective instrument to use in the follow-up of
      patients.

PMID- 17206701
TI  - CD4(+) T lymphocytes mediate colitis in HLA-B27 transgenic rats monoassociated
      with nonpathogenic Bacteroides vulgatus.
AB  - BACKGROUND: HLA-B27/beta2 microglobulin transgenic (TG) rats develop spontaneous
      colitis when raised under specific pathogen-free (SPF) conditions or after mono
      association with Bacteroides vulgatus (B. vulgatus), whereas germ-free TG rats
      fail to develop intestinal inflammation. SPF HLA-B27 TG rnu/rnu rats, which are
      congenitally athymic, remain disease free. These results indicate that commensal
      intestinal bacteria and T cells are both pivotal for the development of colitis
      in TG rats. However, it is not known if T cells are also required in the
      induction of colitis by a single bacterial strain. The aim of this study was
      therefore to investigate the role of T cells in the development of colitis in B.
      vulgatus-monoassociated HLA-B27 TG rats. METHODS: HLA-B27 TG rnu/rnu and rnu/+
      rats were monoassociated with B. vulgatus for 8-12 weeks. CD4(+) T cells from
      mesenteric lymph nodes (MLNs) of B. vulgatus-monoassociated rnu/+ TG donor rats
      were transferred into B. vulgatus-monoassociated rnu/rnu TG recipients. RESULTS:
      B. vulgatus-monoassociated rnu/+ rats showed higher histologic inflammatory
      scores and elevated colonic interferon-gamma mRNA, cecal myeloperoxidase, and
      cecal IL-1beta levels compared to those in rnu/rnu TG rats that did not contain T
      cells. After transfer of CD4(+) cells from colitic B. vulgatus-monoassociated
      rnu/+ TG donor rats, B. vulgatus-monoassociated rnu/rnu TG recipients developed
      colitis that was accompanied by B. vulgatus-induced IFN-gamma production by MLN
      cells in vitro and inflammatory parameters similar to rnu/+ TG rats. CONCLUSIONS:
      These results implicate CD4(+) T cells in the development of colitis in HLA-B27
      TG rats monoassociated with the nonpathogenic bacterial strain B. vulgatus.

PMID- 17206702
TI  - Update on the incidence and prevalence of Crohn's disease and ulcerative colitis
      in Olmsted County, Minnesota, 1940-2000.
AB  - BACKGROUND: We previously reported that the prevalence of Crohn's disease (CD)
      and ulcerative colitis (UC) in Olmsted County, Minnesota, had risen significantly
      between 1940 and 1993. We sought to update the incidence and prevalence of these
      conditions in our region through 2000. METHODS: The Rochester Epidemiology
      Project allows population-based studies of disease in county residents. CD and UC
      were defined by previously used criteria. County residents newly diagnosed
      between 1990 and 2000 were identified as incidence cases, and persons with these
      conditions alive and residing in the county on January 1, 2001, were identified
      as prevalence cases. All rates were adjusted to 2000 US Census figures for
      whites. RESULTS: In 1990-2000 the adjusted annual incidence rates for UC and CD
      were 8.8 cases per 100,000 (95% confidence interval [CI], 7.2-10.5) and 7.9 per
      100,000 (95% CI, 6.3-9.5), respectively, not significantly different from rates
      observed in 1970-1979. On January 1, 2001, there were 220 residents with CD, for
      an adjusted prevalence of 174 per 100,000 (95% CI, 151-197), and 269 residents
      with UC, for an adjusted prevalence of 214 per 100,000 (95% CI, 188-240).
      CONCLUSION: Although incidence rates of CD and UC increased after 1940, they have
      remained stable over the past 30 years. Since 1991 the prevalence of UC decreased
      by 7%, and the prevalence of CD increased about 31%. Extrapolating these figures
      to US Census data, there were approximately 1.1 million people with inflammatory
      bowel disease in the US in 2000.

PMID- 17206703
TI  - Predictors of early response to infliximab in patients with ulcerative colitis.
AB  - BACKGROUND: Our objective is to report the outcome of infliximab (IFX) in
      ulcerative colitis (UC) patients from a single center and to identify predictors
      of early clinical response. METHODS: The first 100 UC patients (45 female; median
      age, 37.9 years) who received IFX at a single center were included. Eighty-four
      patients received 5 mg/kg IFX, and 37 patients received a 3-dose IFX induction at
      weeks 0, 2, and 6. The Mayo endoscopic subscore, assessed by sigmoidoscopy before
      inclusion, was 1, 2, and 3 in 5%, 52%, and 43% of patients, respectively. Sixty
      percent had pancolitis, 63% were on concomitant immunosuppressive therapy, 9%
      were active smokers, 64% had C-reactive protein > or =5 mg/dL, and 44% were
      pANCA+/ASCA-. Five patients received IFX because of severe acute colitis
      refractory to intravenous corticosteroids. RESULTS: Early complete and partial
      clinical responses were observed in 41% and 24% of patients. Patients with early
      clinical response were significantly younger than nonresponders (median age, 35.7
      versus 41.6 years, P = 0.041). Patients who were pANCA+/ASCA- had a significantly
      lower early clinical response (55% versus 76%; odds ratio [OR] = 0.40 (0.16
      0.99), P = 0.049). Concomitant immunosuppressive therapy and the use of an IFX
      induction scheme did not influence early clinical response. Only 1 of 5 patients
      who received IFX for acute steroid-refractory colitis required colectomy within 2
      months. CONCLUSIONS: IFX is an efficient therapy in UC, as shown by 65% early
      clinical response. A pANCA+/ASCA- serotype and an older age at first IFX infusion
      are associated with a suboptimal early clinical response.

PMID- 17206704
TI  - Extracorporeal elimination of TNF-alpha-producing CD14(dull)CD16(+) monocytes in
      leukocytapheresis therapy for ulcerative colitis.
AB  - BACKGROUND: In recent years leukocytapheresis using a leukocyte removal filter
      (known as lymphocytapheresis, LCAP) has been applied to the treatment of various
      autoimmune diseases including ulcerative colitis (UC). In the present study we
      aimed to clarify how LCAP therapy modifies inflammatory responses by modulating
      circulating TNF-alpha-producing monocytes. METHODS: Mononuclear cells were
      obtained from blood before and after the first treatment, and the expression
      profiles of various immune cells (naive versus. memory, regulatory
      CD4(+)CD25(bright) versus non-regulatory CD4(+)CD25(-) T cells, and CD14(+)CD16(
      ) versus CD14(dull)CD16(+) monocytes) were assessed. To evaluate immunological
      differences between CD14(+)CD16(-) and CD14(dull)CD16(+) monocytes, the
      expression of TNF-alpha, IL-6, IL-12, IL-10, IL-18, surface toll-like receptor 2
      (TLR2), TLR4, and other activation markers including HLA-DR, CD80 and CD86, as
      well as cytokine profiles, were analyzed. RESULTS: LCAP treatment selectively
      removed CD14(dull)CD16(+) monocytes, which preferentially produce TNF-alpha and
      IL-12 and express HLA-DR, CD80, CD86, and TLR2, compared with the major fraction
      of CD14(+)CD16(-) monocytes, which conversely produce a higher amount of IL-10.
      In addition, the CD4(+)CD45RO(+)CD62L(-)/CD4(+)CD45RO(+)CD62L(+) ratio was
      significantly lower after LCAP therapy. However, the CD4(+)CD25(bright)/total
      CD4(+) ratio did not change. CONCLUSIONS: The present findings revealed the real
      target of proinflammatory CD14(dull)CD16(+) monocytes removed during LCAP
      treatment of UC and that LCAP might be used as an extracorporeal anti-TNF-alpha
      therapy, expanding the clinical applications of this procedure to include the
      treatment of Crohn's disease.

PMID- 17206705
TI  - Changes in clinical characteristics, course, and prognosis of inflammatory bowel
      disease during the last 5 decades: a population-based study from Copenhagen,
      Denmark.
AB  - BACKGROUND: It remains uncertain whether the increasing incidence of inflammatory
      bowel disease (IBD) during the last decades has been accompanied by an alteration
      in the presentation, course, and prognosis of the disease. To answer this
      question, 3 consecutive population-based IBD cohorts from Copenhagen, Denmark
      (1962-2005), were assessed and evaluated. METHODS: Phenotype, initial disease
      course, use of medications, cumulative surgery rate, standardized incidence ratio
      of colorectal cancer (CRC), and standardized mortality ratio (SMR) were compared
      in the 3 cohorts, which had a total of 641 patients with Crohn's disease (CD) and
      1575 patients with ulcerative colitis (UC). RESULTS: From 1962 to 2005, the
      proportion of IBD patients suffering from CD increased (P < 0.001), time from
      onset of symptoms to diagnosis of CD decreased (P = 0.001), and median age at
      diagnosis of UC increased (P < 0.01). The prevalence of upper gastrointestinal
      involvement and pure colonic CD varied significantly between cohorts. UC patients
      diagnosed in the 1990s had a higher prevalence of proctitis, received more
      medications, and had a milder initial disease course than did previous patients.
      The surgery rate decreased significantly in CD but not in UC. The risk of CRC in
      IBD was close to expected over the entire period, whereas the mortality of
      patients with CD increased (overall SMR, 1.31; 95% CI, 1.07-1.60). CONCLUSIONS:
      Despite variations in the presentation and initial course of IBD during the last
      5 decades, its long-term prognosis remained fairly stable. Treatment of IBD
      changed recently, and future studies should address the effect of these changes
      on long-term prognosis.

PMID- 17206706
TI  - Controversies surrounding the comorbidity of depression and anxiety in
      inflammatory bowel disease patients: a literature review.
AB  - Psychological disorders are highly prevalent in patients with inflammatory bowel
      disease (IBD). Anxiety and depression are known to independently affect quality
      of life and may additionally impair quality of life in IBD over and above the IBD
      itself. Some researchers have further proposed that anxiety and depression may
      influence the clinical course of IBD. However, despite the potential for anxiety
      and depression to play an important role in the clinical picture of IBD, there is
      little prospective well-controlled research in this area. Probably because of
      this lack of clear data, researchers dispute the actual role of these
      psychological disorders in IBD, with a number of conflicting opinions expressed.
      This article reports on a review of the literature in this field. Herein we
      discuss the five main areas of controversy regarding IBD and the specific
      psychological comorbidities of depression and anxiety: 1) the relative rate of
      cooccurrence of these psychological disorders with IBD; 2) the cooccurrence of
      these psychological disorders with particular phase of IBD; 3) the cooccurrence
      of these psychological disorders with the specific type of IBD; 4) the rate of
      these psychological comorbidities compared both to healthy subjects and to other
      disease states; and 5) the timing of onset of psychological comorbidity with
      respect to onset of IBD. Methodological weaknesses of the reviewed studies make
      it impossible to resolve these controversies. However, the results clearly show
      that anxiety/depression and IBD frequently interact. Given the long-term illness
      burden patients with IBD face, further prospective, appropriately controlled
      studies are needed to adequately answer the question of the precise interplay
      between anxiety/depression and IBD.

PMID- 17206707
TI  - Portal vein thrombosis in ulcerative colitis complicated by bleeding from gastric
      varices.

PMID- 17206708
TI  - Remission-inducing effect of anti-TNF monoclonal antibody in TNBS colitis:
      mechanisms beyond neutralization?
AB  - BACKGROUND: Tumor necrosis factor (TNF) plays an important role in the
      pathogenesis of several inflammatory diseases. Its expression is increased in
      inflamed mucosa of Crohn's disease patients and anti-TNF treatment improves
      mucosal inflammation. Besides neutralization, induction of apoptosis of
      monocytes/macrophages and T cells is thought to be an important mechanism of
      action of the anti-TNF monoclonal antibody therapy. The aim was to investigate
      the pathogenic role of TNF in hapten-induced colitis models and to study the
      relationship between apoptosis induction and disease remission. METHODS: In 2
      murine colitis models (trinitrobenzene sulphonic acid, TNBS, and oxazolone
      colitis), mice were injected daily with anti-TNF monoclonal antibody (mAb).
      Macrophages were collected from lamina propria of TNBS colitis mice. 7AAD and
      anti-active-caspase-3 staining were used to study DNA degradation and
      intracellular caspase activation. A pan-caspase inhibitor, N-benzyloxycarbonyl
      Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK), was given to a subgroup of the
      colitis mice. RESULTS: Treatment with anti-TNF effectively reduced intestinal
      mucosal inflammation in TNBS colitis but not in oxazolone colitis. Effectiveness
      was evidenced by a more rapid recovery of body weight and reduced cell
      infiltration, and downregulation of proinflammatory cytokines interferon-gamma
      (IFN-gamma), TNF, and IL-18 at the mRNA level. Apoptosis was induced in lamina
      propria macrophages after treatment with anti-TNF, and it was abrogated through
      short-term pretreatment with Z-VAD-FMK. CONCLUSION: Anti-TNF downregulates
      proinflammatory cytokines and decreases cell infiltration in the bowel after TNBS
      application. The remission-inducing effect of anti-TNF may partly rely on
      apoptosis induction.

PMID- 17206709
TI  - Oral biopsies from patients with orofacial granulomatosis with histology
      resembling Crohn's disease have a prominent Th1 environment.
AB  - BACKGROUND: Orofacial granulomatosis (OFG) is an idiopathic inflammatory disorder
      of children and young adults whose clinical symptoms include swelling of the lips
      or face, mucosal nodularity (cobblestoning), mucosal tags, hyperplasia of the
      gingivae, and aphthous oral ulcers. Whether some OFG patients with clinical and
      histological characteristics resembling Crohn's disease (CD) are a special group
      (oral CD) or true CD patients with symptoms reaching all the way to the oral
      mucosa remains to be determined. METHODS: In this study oral biopsies from 10
      patients with OFG were analyzed for the presence of T cells, T-cell subsets, B
      cells, and macrophages, as well as cytokines (IL-4, IL-10, IFN-gamma, IL-12, and
      TNF-alpha), chemokines (RANTES and MIP-1alpha), and chemokine receptors (CCR3,
      CCR5, and CXCR3). For comparison, oral tissues from 7 patients with other
      granulomatous diseases were included. RESULTS: Compared with the non-OFG group,
      the OFG group had raised levels of CD4(+) T cells, IFN-gamma, IL-10, and RANTES
      but reduced levels of CD68(+) macrophages outside the granulomas, whereas within
      the granulomas the levels of CD3(+) and CD4(+) T cells and of IFN-gamma were
      raised, but the levels of IL-4 were decreased. These data are indicative of a Th1
      environment within the oral OFG tissues, which resembles that already observed in
      gut CD tissues. CONCLUSIONS: Therefore, it can be concluded that some OFG
      patients have both histopathological and immunopathological features that
      resemble those observed in CD patients.

PMID- 17206710
TI  - Interactions between the toxin Kid of the bacterial parD system and the
      antitoxins Kis and MazE.
AB  - The proteins Kid and Kis are the toxin and antitoxin, respectively, encoded by
      the parD operon of Escherichia coli plasmid R1. Kis prevents the inhibition of E.
      coli cell growth caused by the RNA cleavage activity of Kid. Overproduction of
      MazE, the chromosome-encoded homologue of Kis, has been demonstrated to
      neutralize Kid toxicity to a certain extent in the absence of native Kis. Here,
      we show that a high structural similarity exists between these antitoxins, using
      NMR spectroscopy. We report about the interactions between Kid and Kis that are
      responsible for neutralization of Kid toxicity and enhance autoregulation of parD
      transcription. Native macromolecular mass spectrometry data demonstrate that Kid
      and Kis form multiple complexes. At Kis:Kid ratios equal to or exceeding 1:1, as
      found in vivo in a plasmid-containing cell, various complexes are present,
      ranging from Kid(2)-Kis(2) tetramer up to Kis(2)-Kid(2)-Kis(2)-Kid(2)-Kis(2)
      decamer. When Kid is in excess of Kis, corresponding to an in vivo situation
      immediately after loss of the plasmid, the Kid(2)-Kis(2)-Kid(2) heterohexamer is
      the most abundant species. NMR chemical shift and intensity perturbations in the
      (1)H (15)N HSQC spectra of Kid and Kis, observed when titrating the partner
      protein, show that the interaction sites of Kid and Kis resemble those within the
      previously reported MazF(2)-MazE(2)-MazF(2) complex. Furthermore, we demonstrate
      that Kid(2)-MazE(2) tetramers can be formed via weak interactions involving a
      limited part of the Kis-binding residues of Kid. The functional roles of the
      identified Kid-Kis and Kid-MazE interaction sites and complexes in toxin
      neutralization and repression of transcription are discussed.

PMID- 17206711
TI  - Relationship between 6-mercaptopurine dose and 6-thioguanine nucleotide levels in
      patients with inflammatory bowel disease.
AB  - BACKGROUND: 6-Thioguanine nucleotides (6-TGN) are active metabolites of
      azathioprine (AZA) and 6-mercaptopurine (6MP). Higher remission rates have been
      observed in patients with higher 6-TGN levels. However, many physicians prescribe
      AZA/6MP using milligrams per kilogram (mg/kg) dosing regimens without measuring 6
      TGN levels. The aim of this study was to examine the association between 6MP dose
      and 6-TGN levels. METHODS: We conducted a cross-sectional study of patients
      treated for inflammatory bowel disease (IBD) with AZA or 6MP, whose 6-TGN levels
      were measured. Patients with low or intermediate thiopurine methyl transferase
      (TPMT) activity were excluded. AZA dose was converted to 6MP equivalents. The
      relationship between dose and 6-TGN levels was assessed with the Spearman
      correlation coefficient. We used logistic regression to assess the relationship
      between dose and 6-TGN levels of >230 pmol/8 x 10(8). RESULTS: In this study, 155
      patients met our inclusion criteria (median dose, 1.01 +/- 0.40; range, 0.61-1.41
      mg/kg). There was a weak correlation between 6-TGN levels and the absolute dose
      (rho = 0.18, P = 0.04) and the dose in mg/kg (rho = 0.19, P = 0.03). The
      correlation between mg/kg dosage and 6-TGN levels was slightly stronger in those
      using concomitant 5-aminosalicylate (5-ASA) medications (rho = 0.24, P = 0.02).
      Compared with <1.0 mg/kg per day, doses of > or =1.5 mg/kg per day were strongly
      associated with 6-TGN levels of >230 pmol/8 x 10(8) RBC (adjusted odds ratio [OR]
      = 3.7, 95% confidence interval [CI] = 1.1-11.8). However, only 37% of patients
      receiving > or =1.0 mg/kg per day had 6-TGN levels of >230 pmol/8 x 10(8) RBC.
      CONCLUSIONS: 6MP dose is weakly associated with 6-TGN levels. The use of standard
      mg/kg dosing regimens will result in low 6-TGN levels in most patients.

PMID- 17206712
TI  - Leukocyte scintigraphy compared to intraoperative small bowel enteroscopy and
      laparotomy findings in Crohn's disease.
AB  - BACKGROUND: Leukocyte scintigraphy is a noninvasive investigation to assess
      inflammation. We evaluated the utility of labeled leukocytes to detect small
      bowel inflammation and disease complications in Crohn's disease and compared it
      to whole small bowel enteroscopy and laparotomy findings. METHODS: Scintigraphy
      with technetium-99m exametazime-labeled leukocytes was prospectively performed in
      48 patients with Crohn's disease a few days before laparotomy; 41 also had an
      intraoperative small bowel enteroscopy. The same procedures were performed in 8
      control patients. Independent grading of scans was compared with the results of
      enteroscopy and with surgical, histopathologic, and clinical data. RESULTS: In
      the 8 control patients leukocyte scan, endoscopy, and histopathology were all
      negative for the small bowel. In patients with Crohn's disease and small bowel
      inflammation seen at enteroscopy and/or laparotomy (n = 39) the scan was positive
      in 33. In 8 patients without macroscopic small bowel inflammation, the scan was
      positive for the small bowel in 3 patients; at histology, 2 of 3 had
      inflammation. When combining results for patients and controls, the sensitivity
      of leukocyte scan for macroscopically evident small bowel inflammation was 0.85,
      specificity 0.81, accuracy 0.84, positive predictive value 0.92, and negative
      predictive value 0.68. Scintigraphy detected inflammatory lesions not known
      before laparotomy in 16 of 47 (34%) Crohn's disease patients and showed uptake in
      25 of 35 (71%) bowel strictures. It was diagnostic regarding 4 of 8 abscesses and
      9 of 15 fistulas. In 6 patients (13%) lesions first demonstrated by leukocyte
      scintigraphy were treated during the surgery performed. CONCLUSIONS: Leukocyte
      scintigraphy reliably detects small bowel inflammation in Crohn's disease. It
      gives additional information on the presence of inflammatory lesions in a
      fraction of patients planned for surgery.

PMID- 17206713
TI  - Should rare complications of treatment influence decision-making in ulcerative
      colitis?

PMID- 17206714
TI  - Corneal melt after uneventful cataract surgery in a patient with Crohn's disease.

PMID- 17206715
TI  - Pure ileal Crohn's disease without colonic involvement after a long ileo-colonic
      anastomosis (Lester Martin Procedure) for Hirschsprung's disease: an argument
      favoring a specific sensitivity of the ileum in a subset of patients with Crohn's
      disease.

PMID- 17206716
TI  - Comparative study of eosinophil chemotaxis, adhesion, and degranulation in vitro
      in ulcerative colitis and Crohn's disease.
AB  - BACKGROUND: Eosinophils have been identified in tissues from patients with
      Crohn's disease (CD) and ulcerative colitis (UC) but whether they contribute to
      IBD pathogenesis is unknown. This study aimed to investigate the functional
      activity and morphological aspects of peripheral-blood eosinophils from IBD
      patients compared to those from healthy volunteers (HVs). METHODS: Eosinophils
      from HVs and CD and UC patients were purified using a Percoll gradient and then a
      immunomagnetic cell separator. Functional activity in inactivated and previously
      activated cells was investigated by measuring adhesion to fibronectin and
      chemotaxis to fMLP, and degranulation was measured by release of eosinophil
      peroxidase (EPO). Cell morphology was investigated using electron microscopy.
      RESULTS: Eosinophil adhesion to human fibronectin in both inactivated and PAF
      stimulated and PMA-stimulated eosinophils was markedly higher in patients with CD
      than in either patients with UC or HVs. Similarly, the chemotactic response was
      markedly higher in eosinophils isolated from CD patients than in those isolated
      from UC patients or HVs. Baseline EPO release was higher in eosinophils isolated
      from UC patients than in those isolated from HVs or CD patients. Stimulation with
      fMLP or PMA did not further increase EPO release in cells from UC or CD patients.
      Comparable expression of MAC- 1 and VLA-4 adhesion molecules was observed on the
      surfaces of eosinophils from all groups, and an greater number of granules was
      noted in the eosinophils from UC patients than in those from CD patients.
      CONCLUSIONS: Our results indicate that peripheral-blood eosinophils are
      potentially primed and activated in IBD patients. Whether the differences in the
      morphology and functional responses of eosinophil from UC and CD patients reflect
      differences in disease phenotype remains to be elucidated.

PMID- 17206717
TI  - Impact of interobserver disagreement on phenotype-genotype associations in
      Crohn's disease.
AB  - BACKGROUND: Nonvalidated definitions of disease-related parameters in
      inflammatory bowel disease cause variations in diagnosis and disease
      classification. We determined interobserver agreement on applications of
      definitions of the Vienna Classification variables and computed the potential
      influence of misclassification on genotype/phenotype associations. METHODS: Ten
      records of patients with Crohn's disease (CD) were independently evaluated by 19
      observers using a standardized inflammatory bowel disease documentation system,
      which included the Vienna Classification. Interobserver agreement (IOA) was
      calculated as a percentage of the observers' agreement with a predetermined
      reference observer and by Cohen's kappa. Randomized reclassifications were then
      computed with 10,000 simulation runs using the IOA results and published
      NOD2/CARD15 gene status. A chi-square independence test was calculated for each
      simulation run. RESULTS: IOA for location and behavior was 70% (K = 0.57) and 95%
      (K = 0.91), respectively. IOA for location subgroups ranged from 48% to 88% and
      for behavior from 91% to 97%. By including the results of histopathology into the
      evaluation of location, the overall IOA increased significantly, to 80% (P =
      0.019). Assuming a true genotype/phenotype association, the proportion of studies
      with nonsignificant findings (P > 0.05) because of the observed misclassification
      of location ranged from 13.3% to 63.8% and of behavior from 0.2% to 22.2%,
      depending on a study sample size of 500 or 150 patients respectively.
      CONCLUSIONS: We concluded that there is appreciable interobserver disagreement on
      the location of CD according to the original Vienna Classification that may
      obscure true genotype/phenotype associations. Definitions of disease parameters
      have to be validated before being used as the bases for classifications.

PMID- 17206718
TI  - Importance of early detection of cytomegalovirus infection in refractory
      inflammatory bowel disease.

PMID- 17206719
TI  - Computed tomographic enterography adds information to clinical management in
      small bowel Crohn's disease.
AB  - BACKGROUND: CT enterography yields striking findings in the bowel wall in Crohn's
      disease. These images may help to evaluate whether small bowel narrowing results
      from active disease requiring anti-inflammatory therapy. However, the clinical
      relevance of these images is unknown. It is also not known if these radiologic
      findings correlate with objective biomarkers of inflammation. METHODS: In a
      blinded and independent evaluation, IBD subspecialty gastroenterologists reviewed
      clinical data, and CT radiologists reviewed CT enterography scans of 67
      consecutive patients with Crohn's disease and suspicion of either small bowel
      inflammation or stricture. Comparisons were made between (1) clinical and
      radiologic assessments of inflammation and stricture, (2) clinical assessments
      before and after computed tomographic enterography (CTE) reports were revealed,
      and (3) radiologic findings and objective biomarkers of inflammation. RESULTS:
      (1) Individual CTE findings correlated poorly (Spearman's rho < 0.30) with
      clinical assessment; (2) clinicians did not suspect 16% of radiologic strictures,
      and more than half the cases of clinically suspected strictures did not have them
      on CTE; (3) CTE data changed clinicians' perceptions of the likelihood of steroid
      benefit in 41 of 67 cases; (4) specific CTE findings correlated with CRP, and a
      distinct set of CTE findings correlated with ESR in the subset of patients who
      had these biomarkers measured. CONCLUSIONS: CTE seems to add unique information
      to clinical assessment, both in detecting additional strictures and in changing
      clinicians' perceptions of the likelihood of steroids benefiting patients. The
      biomarker correlations suggest that CTE is measuring real biologic phenomena that
      correlate with inflammation, providing information distinct from that in a
      standard clinical assessment.

PMID- 17206720
TI  - Clinical epidemiology of inflammatory bowel disease in Lebanon.
AB  - BACKGROUND: The objectives of this study were to determine the prevalence and
      incidence of inflammatory bowel disease (IBD) in a representative Lebanese cohort
      and to describe practice prevalence trends, disease characteristics, and impact
      on quality of life (QoL) of IBD patients in Lebanon. METHODS: All of a university
      based health program's 2000-2004 computerized records that listed a diagnosis of
      Crohn's disease (CD) or ulcerative colitis (UC) were reviewed. In addition, data
      on patients seen in the gastroenterology clinics and data from the IBD registry
      at the American University of Beirut Medical Center (AUBMC) from the same period
      were analyzed. RESULTS: Of 15,073 insured individuals, 8 had a diagnosis of CD
      and 16 of UC, giving an age-adjusted prevalence of 53.1 per 100,000 people for CD
      and 106.2 per 100,000 people for UC. The mean age at diagnosis for patients with
      CD and UC was 28.8 +/- 11.1 and 32.0 +/- 13.4 years, respectively, and there was
      a slight female predominance. The mean annual incidence was 4.1 per 100,000
      people for UC and 1.4 per 100,000 people for CD (range, 0-6.9/100,000 for both).
      Of the 10,383 patients seen in the gastroenterology clinic from 2000 to 2004, 251
      (2.4%) had IBD (142 UC, 100 CD, and 9 indeterminate), a ratio that trended upward
      over time (range, 1.8%-2.7%). The median IBD Quality-of-Life (IBDQ) questionnaire
      score was 124.9 +/- 30.5, indicating that the disease had a moderately severe
      impact on QoL. CONCLUSIONS: The prevalence of IBD in this representative Lebanese
      cohort falls in the intermediate range of that reported for white populations in
      Europe and North America. Future studies are needed to examine local risk
      factors, disease genotypes and phenotypes, and epidemiologic time trends. The
      psychosocial burden of IBD in Lebanon appears significant.

PMID- 17206721
TI  - Serum lipopolysaccharide-binding protein in endotoxemic patients with
      inflammatory bowel disease.
AB  - BACKGROUND: In inflammatory bowel disease (IBD), enhanced inflammatory activity
      in the gut is thought to increase the risk of bacterial translocation and
      endotoxemia. By searching for signs of endotoxin-signaling cascade activation,
      including augmented levels of endotoxin, lipopolysaccharide-binding protein
      (LBP), and soluble CD14 receptor (sCD14), this prospective study sought to
      establish whether endotoxemia could contribute to greater clinical activity of
      disease. METHODS: Concentrations of plasma endotoxin, LBP, sCD14, several
      cytokines, acute phase proteins and clinical activity indices were determined in
      104 patients with Crohn's disease (CD) and 52 patients with ulcerative colitis
      (UC). RESULTS: Endotoxemia was present in 48% of the patients with CD and in 28%
      of the patients with UC. The mean LBP was higher in patients with active CD (23.1
      +/- 13.7 microg/mL) and UC (21.4 +/- 10.9 microg/mL) than in healthy controls
      (7.2 +/- 1.8 microg/mL; P < 0.01). Elevated serum concentrations of endotoxin and
      LBP were even detected in patients with inactive CD. Among the patients with
      active IBD, those with higher endotoxin levels had the worst clinical activity
      scores and the highest LBP levels. Treatment normalized LBP concentrations, from
      29.1 +/- 13.0 to 15.2 +/- 7.3 microg/mL; (P < 0.05) in active CD and from 21.7 +/
      9.8 to 13.6 +/- 5.7 microg/mL; (P < 0.01) in active UC, along with normalizing
      endotoxin and sCD14 plasma concentrations. CONCLUSIONS: Patients with IBD show
      increased serum levels of endotoxin, LBP and sCD14. This alteration correlates
      with disease activity, with normal levels recovered after treatment, although
      less completely in Crohn's disease, and parallels a rise in proinflammatory
      cytokines, suggesting a contribution of bacterial products to the inflammatory
      cascade in these patients.

PMID- 17206722
TI  - Clinical features and natural history of ulcerative colitis in Korea.
AB  - BACKGROUND: The clinical characteristics of ulcerative colitis (UC) in Asian
      populations have not been well characterized. We therefore investigated the
      clinical features and natural history of UC in Korea. METHODS: We retrospectively
      analyzed 304 Korean patients with UC first diagnosed at the Asan Medical Center
      between June 1989 and August 2005. RESULTS: The male-to-female ratio of the
      patients was 0.94:1, and their median age at diagnosis was 40.0 years (range, 12
      72 years). At diagnosis, proctitis was noted in 134 patients (44.1%), left-sided
      colitis in 69 patients (22.7%), and extensive colitis in 101 patients (33.2%).
      Disease activity at diagnosis was mild in 149 patients (49.0%), moderate in 125
      patients (41.1%), and severe in 26 patients (8.6%). In addition, 4 asymptomatic
      patients (1.3%) were detected as a result of a screening colonoscopy. Clinical
      remission after the first attack was documented in 97.4% of patients. The
      cumulative relapse rate after 1, 5, and 10 years was 30.2%, 72.0%, and 88.4%,
      respectively. The cumulative risk of proximal extension in patients with
      proctitis or left-sided colitis was 33.0% after 5 years and 44.5% after 10 years.
      The cumulative probability of colectomy was 2.0% after 1 year, 2.8% after 3
      years, and 3.3% after 5 to 15 years. The cumulative survival rate after 1, 5, and
      10 years was 100%, 99.4%, and 97.4%, respectively. CONCLUSIONS: The clinical
      features of Korean UC patients at diagnosis are similar to those of Westerners.
      However, UC in Koreans may have a milder course than in Westerners, as indicated
      by the lower rate of colectomy among Koreans.

PMID- 17206723
TI  - Predictive model for the outcome of infliximab therapy in Crohn's disease based
      on apoptotic pharmacogenetic index and clinical predictors.
AB  - BACKGROUND: Infliximab (IFX) is an effective therapy for refractory luminal and
      fistulizing Crohn's disease (CD). Predictors of response could improve selection
      of patients with a higher probability of favorable outcomes and could improve the
      safety profile. We aimed to develop a predictive model for the response to
      infliximab in CD. METHODS: Genetic and clinical data collected in a previous
      pharmacogenetic study of apoptosis genes were analyzed using SAS Enterprise miner
      modeling software and SPSS 12.0. We proposed a novel apoptotic pharmacogenetic
      index (API) with a score ranging from 0 (low apoptotic response) to 3 (high
      apoptotic response) and subsequently developed a decision tree model. RESULTS:
      Response and remission rates significantly increased with API score (P = 0.005 in
      the group of patients with luminal CD, P = 0.02 in the group of patients with
      fistulizing CD). Patients with an API < or = 1 (n = 59) had the lowest response
      and remission rates in both the luminal CD (50% and 39.5%, respectively) and
      fistulizing CD (61.9% and 28.6%, respectively) groups, compared to those with an
      API of 2 (n = 158), whose response and remission rates were 73.8% and 56.1%,
      respectively, in the luminal CD group and 85.7% and 44.9%, respectively, in the
      fistulizing CD group; and those with an API of 3 (n = 10), whose response and
      remission rates were 100% and 85.7%, respectively, in the luminal CD group and
      100% and 0% in the fistulizing CD group. Response in patients with an API < or =
      1 was significantly influenced by concurrent azathioprine therapy in the luminal
      CD (21.4% versus 78.9%, P < 0.001) and in the fistulizing CD (46.6% versus 100%,
      P = 0.04) groups. In patients with an API of 2, we saw an interaction with age
      older than 40 years and location of disease (response 52.2% versus 83.9%, P =
      0.008) in the luminal CD group and with baseline CRP greater than 5 mg/L (73.9%
      versus 93.9%, P = 0.04) in the fistulizing CD group. CONCLUSIONS: From our newly
      proposed apoptotic pharmacogenetic index and clinical predictors, we developed a
      model for prediction of low, medium, and high responses to the first infusion of
      IFX in patients with CD. Further studies are needed to confirm the hypothesis
      generated by our study.

PMID- 17206724
TI  - Prediction of side-chain conformations on protein surfaces.
AB  - An approach is described that improves the prediction of the conformations of
      surface side chains in crystal structures, given the main-chain conformation of a
      protein. A key element of the methodology involves the use of the colony energy.
      This phenomenological term favors conformations found in frequently sampled
      regions, thereby approximating entropic effects and serving to smooth the
      potential energy surface. Use of the colony energy significantly improves
      prediction accuracy for surface side chains with little additional computational
      cost. Prediction accuracy was quantified as the percentage of side-chain dihedral
      angles predicted to be within 40 degrees of the angles measured by X-ray
      diffraction. Use of the colony energy in predictions for single side chains
      improved the prediction accuracy for chi(1) and chi(1+2) from 65 and 40% to 74
      and 59%, respectively. Several other factors that affect prediction of surface
      side-chain conformations were also analyzed, including the extent of
      conformational sampling, details of the rotamer library employed, and accounting
      for the crystallographic environment. The prediction of conformations for polar
      residues on the surface was generally found to be more difficult than those for
      hydrophobic residues, except for polar residues participating in hydrogen bonds
      with other protein groups. For surface residues with hydrogen-bonded side chains,
      the prediction accuracy of chi(1) and chi(1+2) was 79 and 63%, respectively. For
      surface polar residues, in general (all side-chain prediction), the accuracy of
      chi(1) and chi(1+2) was only 73 and 56%, respectively. The most accurate results
      were obtained using the colony energy and an all-atom description that includes
      neighboring molecules in the crystal (protein chains and hetero atoms). Here, the
      accuracy of chi(1) and chi(1+2) predictions for surface side chains was 82 and
      73%, respectively. The root mean square deviations obtained for hydrogen-bonding
      surface side chains were 1.64 and 1.81 A, with and without consideration of
      crystal packing effects, respectively.

PMID- 17206725
TI  - Primary small cell carcinoma of the pancreas with an unusual sonographic
      appearance.
AB  - We present a case of primary pancreatic small cell carcinoma with an unusual
      sonographic feature. A 75-year-old woman presented with poor appetite and weight
      loss. Abdominal sonographic examination revealed a diffusely enlarged pancreas
      with relative increased echogenicity and smooth contour. CT also confirmed the
      diffuse infiltrative pattern of the tumor. The diagnosis was confirmed via
      sonographically guided biopsy. The tumor was composed of small cells with
      hyperchromatic nuclei and scanty cytoplasm infiltrating the pancreatic tissue,
      consistent with small cell carcinoma of the pancreas. Primary pancreatic small
      cell carcinoma rarely presents as the diffuse infiltrating type. These unusual
      sonographic features must be differentiated from other pancreatic tumors
      presenting as diffuse pancreatic enlargement.

PMID- 17206726
TI  - Role of second trimester sonography in detecting trisomy 18: a review of 70
      cases.
AB  - PURPOSE: To investigate the role of second-trimester sonographic examination in
      the prenatal diagnosis of trisomy 18. METHODS: Out of 22,150 fetal chromosomal
      analyses performed between 1990 and 2004, 70 trisomy 18 fetuses were found. The
      sonographic findings of this aneuploidy were analyzed. RESULTS: The average
      maternal age was 32.4 years; the average gestational age was 19.5 weeks. Major
      anomalies were seen in 61 (87.1%) of the 70 fetuses with trisomy 18; among these,
      cardiac anomalies were the most common (47.1%), with a 27.1% incidence of
      ventricular septal defects. Anomalies of the central nervous system were seen in
      35.7% of cases; abnormal head shape was the most frequently detected anomaly in
      this group (12.9%). Fifty-six (80%) of the fetuses had at least 1 minor anomaly;
      of these, choroid plexus cyst was the most common (38.6%). Increased nuchal fold
      thickness was detected in 17.1% of cases. CONCLUSION: The vast majority of
      trisomy 18 fetuses have sonographically detectable abnormalities in the second
      trimester. Both the 87.1% frequency of major anomalies and the 80% frequency of
      minor anomalies are substantially higher than multiple biochemical marker tests
      could achieve. It was also demonstrated that fetal echocardiography plays a
      pivotal role in the diagnosis of trisomy 18.

PMID- 17206727
TI  - Sonographic diagnosis of thyroid nodules: correlation with the results of
      sonographically guided fine-needle aspiration biopsy.
AB  - PURPOSE: To assess the reliability of sonography in differentiating benign from
      malignant thyroid nodules and selecting lesions for fine-needle aspiration (FNA).
      METHODS: During a 2-year period, the following 7 sonographic parameters were
      assessed in 129 patients with thyroid nodules: size, number, echogenicity,
      echotexure, margin regularity, presence of calcifications, and presence of a
      hypoechoic rim. Sonographically guided FNA was performed on thyroid nodules 5 mm
      in diameter. Out of 184 FNAs, we obtained 168 specimens adequate for cytologic
      analysis and 16 (9%) nondiagnostic specimens. RESULTS: FNA diagnoses included 150
      (89%) benign and 18 (11%) malignant nodules. Among 53 solitary nodules, 11 were
      carcinomas and 42 were benign (p < 0.01). The mean size of the carcinomas was 28
      +/- 12 mm versus 18 +/- 10 mm for benign nodules (p < 0.01). The following
      sonographic features were significantly associated with malignancy:
      hypoechogenicity, irregular margins, calcifications, and absence of a hypoechoic
      rim. Differences in echotexure between malignant and benign nodules were not
      statistically significant. CONCLUSION: Sonographically guided FNA should be
      performed on thyroid nodules 5 mm in diameter with sonographic characteristics
      that suggest malignancy.

PMID- 17206728
TI  - Large cystic infiltrating ductal carcinoma in male breast.
AB  - Cystic infiltrating ductal carcinoma is a very rare entity that, to the best of
      our knowledge, has not yet been reported in males. We report the sonographic and
      CT findings of a large cystic infiltrating ductal carcinoma in a 51-year-old man.
      Cystic infiltrating ductal carcinoma is a very rare entity that, to the best of
      our knowledge, has not yet been reported in males. We report the sonographic and
      CT findings of a large cystic infiltrating ductal carcinoma in a 51-year-old man.

PMID- 17206729
TI  - Elaboration of neosamine rings in the biosynthesis of neomycin and butirosin.
AB  - The proteins Neo-11 and Neo-18 encoded in the neomycin gene cluster (neo) of
      Streptomyces fradiae NCIMB 8233 have been characterized as glucosaminyl-6'
      oxidase and 6'-oxoglucosaminyl:L-glutamate aminotransferase, respectively. The
      joint activity of Neo-11 and Neo-18 is responsible for the conversion of
      paromamine to neamine in the biosynthetic pathway of neomycin through a mechanism
      of FAD-dependent dehydrogenation followed by a pyridoxal-5'-phosphate-mediated
      transamination. Neo-18 is also shown to catalyze deamination at C-6''' of
      neomycin, thus suggesting bifunctional roles of the two enzymes in the formation
      of both neosamine rings of neomycin. The product of the btrB gene, a homologue of
      neo-18 in the butirosin biosynthetic gene cluster (btr) in Bacillus circulans,
      exhibits the same activity as Neo-18; this indicates that there is a similar
      reaction sequence in both butirosin and neomycin biosynthesis.

PMID- 17206731
TI  - Self-organization of InAs quantum-dot clusters directed by droplet homoepitaxy.

PMID- 17206732
TI  - CdSe nanocrystals as hydroperoxide scavengers: a new approach to highly sensitive
      quantification of lipid hydroperoxides.

PMID- 17206730
TI  - Surface-plasmon-resonance-based chemical proteomics: efficient specific
      extraction and semiquantitative identification of cyclic nucleotide-binding
      proteins from cellular lysates by using a combination of surface plasmon
      resonance, sequential elution and liquid chromatography-tandem mass spectrometry.
AB  - Chemical proteomics is a powerful methodology for identifying the cellular
      targets of small molecules, however, it is biased towards abundant proteins.
      Therefore, quantitative strategies are needed to distinguish between specific and
      nonspecific interactions. Here, we explore the potential of the combination of
      surface plasmon resonance (SPR) coupled to liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) as an alternative approach in chemical proteomics. We
      coupled cGMP molecules to the SPR chip, and monitored the binding and
      dissociation of proteins from a human lysate by using sequential elution steps
      and SPR. The eluted proteins were subsequently identified by LC-MS/MS. Our
      approach enabled the efficient and selective extraction of low-abundant cyclic
      nucleotide-binding proteins such as cGMP-dependent protein kinase, and a
      quantitative assessment of the less- and nonspecific competitive binding
      proteins. The data show that SPR-based chemical proteomics is a promising
      alternative for the efficient specific extraction and quantitative identification
      of small-molecule-binding proteins from complex mixtures.

PMID- 17206733
TI  - Derivatives of Iressa, a specific epidermal growth factor receptor inhibitor, are
      powerful apoptosis inducers in PC3 prostatic cancer cells.
AB  - The tyrosine kinase activity of the epidermal growth factor receptor (EGFR) is
      widely involved in signaling pathways and often deregulated in cancer. Its role
      in the development of prostate cancer is well established, and therapeutic
      strategies such as blockade of the intracellular tyrosine kinase domain with
      small-molecule tyrosine kinase inhibitors have been proposed. Herein we describe
      the synthesis and in vitro pharmacological properties of C6- and C7-substituted 4
      anilinoquinazolines, analogues of Iressa and powerful proapoptotic inducers in
      hormone-independent prostate cancer PC3 cell lines.

PMID- 17206734
TI  - Combined mass spectrometry and dynamic chemistry approach to identify
      metalloenzyme inhibitors.

PMID- 17206736
TI  - Intra- and intermolecular reactions of indoles with alkynes catalyzed by gold.
AB  - Indoles react intramolecularly with alkynes in the presence of gold catalysts to
      give from six- to eight-membered-ring annulated compounds. The cationic Au(I)
      complex [Au(P{C(6)H(4)(o-Ph)}(tBu)(2))(NCMe)]SbF(6) is the best catalyst for the
      formation of six- and seven-membered rings by 6-endo-dig, 6-exo-dig, and 7-exo
      dig cyclizations. Indoloazocines are selectively obtained with AuCl(3) as
      catalyst in a rare 8-endo-dig process. In this process allenes or tetracyclic
      annulated derivatives are also formed as a result of an initial fragmentation
      reaction. The intermolecular reaction of indoles with alkynes proceeds to form 3
      alkenylated intermediates that react with a second equivalent of indole to give
      bisindolyl derivatives. Indoles that are substituted at the 3-position react
      intermolecularly with alkynes to give 2-alkenylated intermediates that can be
      trapped intramolecularly with the appropriate nucleophiles.

PMID- 17206735
TI  - The enhancement effect of gold nanoparticles in drug delivery and as biomarkers
      of drug-resistant cancer cells.
AB  - The enhancement effect of 3-mercaptopropionic acid capped gold nanoparticles
      (NPs) in drug delivery and as biomarkers of drug-resistant cancer cells has been
      demonstrated through fluorescence microscopy and electrochemical studies. The
      results of cell viability experiments and confocal fluorescence microscopy
      studies illustrate that these functionalized Au NPs could play an important role
      in efficient drug delivery and biomarking of drug-resistant leukemia K562/ADM
      cells. This could be explored as a novel strategy to inhibit multidrug resistance
      in targeted tumor cells and as a sensitive method for the early diagnosis of
      certain cancers. Our observations also indicate that the interaction between the
      functionalized Au NPs and biologically active molecules on the surface of
      leukemia cells may contribute the observed enhancement in cellular drug uptake.

PMID- 17206739
TI  - LC/MS characterization of undesired products formed during iodoacetamide
      derivatization of sulfhydryl groups of peptides.
AB  - Many undesired by-products have been noticed during alkylation with
      iodoacetamide, a widely used derivatization reaction in proteomics for the
      determination of sulfhydryl groups in peptides and proteins. We report here that
      iodoacetamide reacts with the N-terminal NH2 and the C-terminal carboxylic acid
      groups, in addition to the peripheral residues bearing protic functional groups.
      If sufficient reaction time is given, the N-terminal NH2 group is readily
      dialkylated by iodoacetamide. In fact, the N-terminal NH2 group reacts even
      faster than the reactive sites present in residues, such as tyrosine or
      histidine. LC/MS investigations with certain reactive peptides show that by
      products are formed in a relatively short reaction time, even at room
      temperature. Interestingly, derivatives formed in this way are useful for
      sequence determination of peptides by MS since the intensities of y'' ions are
      highly suppressed in the spectra of N-terminus mono- and dialkylated peptides,
      whereas those of b-ions are significantly enhanced. For example, in the spectrum
      of N,N-dicarboxamidomethyl derivative of Val-Ala-Ala-Phe (VAAF), the y-series
      ions are virtually absent. On the other hand, when the derivatization takes place
      at the carboxylic group, the y-series ions are markedly observed in the spectra
      of these undesired O-carboxamidomethyl derivatives.

PMID- 17206740
TI  - Using electrospray-assisted pyrolysis ionization/mass spectrometry for the rapid
      characterization of trace polar components in crude oil, amber, humic substances,
      and rubber samples.
AB  - We describe the use of electrospray-assisted pyrolysis ionization/mass
      spectrometry (ESA-Py/MS) to selectively ionize trace polar compounds that coexist
      with large amounts of nonpolar hydrocarbons in crude oil, amber, humic
      substances, and rubber samples. Samples of different origins are distinguished
      rapidly by their positive ion ESA-Py mass spectra without prior separation or
      chemical pretreatment. During ESA-Py analysis, the samples in their solid or
      liquid states were pyrolyzed at 590, 630 or 940 degrees C using a commercial
      Curie-point pyrolysis probe. The gaseous pyrolysates were transferred into a
      glass reaction cell. The polar compounds (M) in the pyrolysates were then ionized
      by electrospray ionization (ESI), yielding protonated molecules (MH+). Although
      the major components of the pyrolysates are nonpolar hydrocarbons, their lack of
      functional groups that can receive a proton in the ESA-Py source results in no
      hydrocarbon ion signals being produced; thus, the positive ions detected in ESA
      Py mass spectra all result from trace polar components in the pyrolysates.

PMID- 17206741
TI  - Use of a variably sensitive selected reaction monitoring method to extend the
      linear dynamic range for quantitative high-performance liquid
      chromatography/tandem mass spectrometry.
AB  - A method has been devised with the capacity to extend the linear dynamic range of
      a triple quadrupole mass spectrometer operated in the selected reaction
      monitoring (SRM) mode of analysis. This extended range experiment can be realized
      by simultaneously acquiring variably sensitive data, via collision energy
      adjustment, for the same precursor-to-product ion transition within a single SRM
      method. While this method can be applied universally to many different study
      types without any detrimental effect to the analysis or throughput, it was
      applied herein to acquire and quantify, within a single analysis, the
      concentrations of GSK-A in a multiple-dose rodent study, that previously required
      a dilution scheme. Using this methodology, the linear dynamic range of GSK-A was
      increased over traditional methods by nearly two orders of magnitude, from 2.00
      10,000 ng/mL to 0.500-100,000 ng/mL.

PMID- 17206742
TI  - Photodissociation at 193 nm of some singly protonated peptides and proteins with
      m/z 2000-9000 using a tandem time-of-flight mass spectrometer equipped with a
      second source for delayed extraction/post-acceleration of product ions.
AB  - A tandem time-of-flight mass spectrometer was built for photodissociation (PD) of
      singly protonated peptides and small proteins generated by matrix-assisted laser
      desorption/ionization. PD was performed in a second source after deceleration of
      precursor ions. The delayed extraction/post-acceleration scheme was used for the
      product ions. For the PD at 193 nm of small singly protonated peptides, the
      present instrument showed much better sensitivity and resolution for product ions
      than the previous one (Moon JH, Yoon SH, Kim MS, Bull. Korean Chem. Soc. 2005;
      26: 763) even though the overall spectral patterns obtained with the two
      instruments were similar. The present instrument was inferior in precursor ion
      selection and background noise level. PD was achieved for precursor ions as large
      as the singly protonated ubiquitin (m/z 8560.63), indicating that the
      photoexcitation is capable of supplying a sufficient amount of internal energy to
      dissociate large singly protonated proteins. As the precursor ion m/z increased,
      however, product ion signals deteriorated rather rapidly. As in the PD of small
      peptide ions with m/z around 1000, the types of the product ions generated from
      singly protonated peptides with m/z in the range 2000-4000 were mostly determined
      by the positions of arginine residues. Namely, a(n) and d(n) ions dominated when
      an arginine residue(s) was near the N-terminus while v(n), w(n), x(n) and y(n)
      dominated when the same residue(s) was near the C-terminus. In addition, d(n),
      v(n) and w(n) ions were generated according to the correlation rules previously
      observed in the collisionally activated dissociation. Isoleucine and leucine
      isomers could be easily distinguished based on the w(n) and d(n) ions.

PMID- 17206743
TI  - Data-dependent tandem mass spectrometry of doubly protonated molecules in
      pharmaceutical analysis.

PMID- 17206744
TI  - High-throughput direct-infusion ion trap mass spectrometry: a new method for
      metabolomics.
AB  - A fast method was developed to directly infuse raw plant extracts into a linear
      ion trap mass spectrometer, using the ion trap to isolate and fragment as many
      ions as possible from the extract. The full mass spectra can be analysed by
      multivariate statistics to determine discriminating ions, and the fragmentation
      data allows rapid classification or identification of these ions. The methodology
      was used to screen a wide range of strains of endophytic fungi in perennial
      ryegrass seeds for differences in metabolic profiles. The results show that this
      newly developed methodology is able to determine discriminating ions that can be
      present in very low concentrations. It also yielded sufficient fragmentation data
      to classify or identify the discriminating ions.

PMID- 17206745
TI  - An electrospray membrane probe for the analysis of volatile and semi-volatile
      organic compounds in water.
AB  - A new membrane probe incorporating electrospray ionization (ESI) was designed,
      built and coupled to an ion trap mass spectrometer to detect low levels of semi
      volatile organic compounds (SVOCs) in water. Similar to other membrane
      introduction mass spectrometry (MIMS) systems, the probe contains a capillary
      polydimethylsiloxane (PDMS) membrane to allow for the preferential permeation of
      small molecules but, in contrast, the interface uses a liquid/membrane/liquid
      interface rather than liquid/membrane/gas. The ESI source allows the probe to be
      operated at atmospheric pressure in positive or negative ionization mode and the
      lack of fragmentation in ESI allows for the simultaneous screening of many
      analytes with high sensitivity. The interface allows for the addition of
      additives to both the external and the internal liquid mobile phases to
      selectively improve permeation and/or the ionization efficiency of various
      classes of compounds. Characterization of the probe with methanol as the internal
      mobile phase showed that the signal for aniline optimized at 60 degrees C and an
      internal flow rate between 2-5 microL/min. The transfer of analyte through the
      membrane from water to methanol ensures a strong signal and robust electrospray
      for both positive and negative ion mode which is not typical when spraying pure
      water. Detection limits for aniline, pyridine and pentachlorophenol, and for the
      herbicides alachlor, atrazine, butachlor, metolachlor and simazine, were in the
      ppb to pptr range.

PMID- 17206746
TI  - The venom of the snake genus Atheris contains a new class of peptides with
      clusters of histidine and glycine residues.
AB  - We investigated venoms from members of the genus Atheris (Serpentes, Viperidae),
      namely the rough scale bush viper (Atheris squamigera), the green bush viper (A.
      chlorechis) and the great lakes bush viper (A. nitschei), using mass spectrometry
      based strategies, relying on matrix-assisted laser desorption/ionisation time-of
      flight mass spectrometry (MALDI-TOF-MS) and electrospray ionisation tandem mass
      spectrometry (ESI-MS/MS) with de novo peptide sequencing. We discovered a set of
      novel peptides with masses in the 2-3 kDa range and containing poly-His and poly
      Gly segments (pHpG). Complete primary structural elucidation and confirmation of
      two sequences by Edman degradation indicated the consensus sequence
      EDDH(9)GVG(10). Bioinformatic investigations in protein sequence databanks did
      not show relevant homology with known peptides or proteins. However, a more
      extensive investigation of data in nucleic acid databases revealed some
      similarities to the precursor sequences of bradykinin potentiating peptides (BPP)
      and C-type natriuretic peptides (CNP), agents that are known to affect the
      cardiovascular system by acting on specific metalloproteases and receptors. The
      novel pHpG peptides found in Atheris venoms might also act on the cardiovascular
      system by inhibiting particular metalloproteases, which however remain to be
      identified.

PMID- 17206747
TI  - Resin-packed nanoelectrospray in combination with video and mass spectrometry for
      the direct and real-time molecular analysis of mast cells.
AB  - A nano-electrospray ionization (nanoESI) emitter for analysis of a biological
      solution was developed by packing a nanoESI needle with two types of resins for
      desalting and preconcentration of target molecules. Determination of secreted
      histamine and serotonin molecules in cell culture buffers was demonstrated using
      5-methyltryptamine as internal standard. The results showed good linearity of
      target signals in the concentration range from 0.25 to 50.0 ng/mL of histamine or
      serotonin. These molecules were monitored to be secreted by A23187 (calcium
      ionophore) stimulant in rat peritoneal mast cells. Using a combination of a video
      microscope and a mass spectrometer, we could visualize exocytotic moments and
      analyze secreted molecules by mass spectrometry simultaneously. Time-dependent
      release of histamine and serotonin from activated mast cells showed that
      significant production of these molecules occurred and reached a maximal level at
      15 min for serotonin and at 30 min for histamine, respectively. These results
      showed that this method allows the direct and timely analysis of secreted
      molecules in biological responses.

PMID- 17206748
TI  - Early stopping clinical trials of binomial response with an exact group
      sequential method.
AB  - In Phase II clinical trials much slower patient enrollment and intervening
      results of comparable trials can make it desirable to stop trials early when the
      data indicate no relevant effect. For a binomial response, we adopt an exact
      group sequential method as a decision tool to assess whether the trial could be
      stopped early or not. We have applied the exact group sequential method to a
      Phase II Tuberculosis clinical trial, and the results have been compared with
      that from error spending and conditional power approaches. We conclude that the
      exact group sequential method is more efficient for interim analysis in clinical
      trials than the error spending and conditional power approaches. Published in
      2007 by John Wiley & Sons, Ltd.

PMID- 17206750
TI  - Recent advances in hepatitis B virus research: a German point of view.
AB  - More than 30 years after the discovery of human hepatitis B virus (HBV) this
      virus remains to be one of the major global health problems. In infected
      adolescents or adults, 5%-10% will lead to a chronic carrier state, whereas in
      infected neonates up to 90% develop chronicity. It is estimated that about 370
      million people are chronic carriers of HBV worldwide. In many regions of the
      world, chronic HBV infection is still the major cause of liver cirrhosis and
      hepatocellular carcinoma. During the last 30 years, many steps of the viral life
      cycle have been unravelled, mainly due to cloning, sequencing and expression of
      the genomic DNA extracted from HBV virions. This has lead to the development of a
      safe and efficient vaccine and sensitive tests for HBV surface protein (HBsAg)
      allowing reliable diagnosis and screening of blood products. More recently, a
      growing number of reverse transcriptase inhibitors have been developed. However,
      together with these improvements new deficiencies in prevention and cure of HBV
      infections are becoming apparent. Although HBV is a DNA virus, it is highly
      variable under immunity or drug induced selection pressure, resulting in vaccine
      related escape mutants and drug resistance. To overcome these challenging
      problems new antivirals and optimised vaccines have to be developed.

PMID- 17206749
TI  - Nutritional modulation of the inflammatory response in inflammatory bowel disease
      -from the molecular to the integrative to the clinical.
AB  - Nutrient deficiencies are common in patients with inflammatory bowel disease
      (IBD). Both total parenteral and enteral nutrition provide important supportive
      therapy for IBD patients, but in adults these are not useful for primary therapy.
      Dietary intervention with omega-3 polyunsaturated fatty acids contained in fish
      oil may be useful for the care of IBD patients, and recent studies have stressed
      the role of PPAR on NFkappaB activity on the potential beneficial effect of
      dietary lipids on intestinal function.

PMID- 17206751
TI  - Hepatitis B virus taxonomy and hepatitis B virus genotypes.
AB  - Hepatitis B virus (HBV) is a member of the hepadnavirus family. Hepadnaviruses
      can be found in both mammals (orthohepadnaviruses) and birds (avihepadnaviruses).
      The genetic variability of HBV is very high. There are eight genotypes of HBV and
      three clades of HBV isolates from apes that appear to be additional genotypes of
      HBV. Most genotypes are now divided into subgenotypes with distinct virological
      and epidemiological properties. In addition, recombination among HBV genotypes
      increases the variability of HBV. This review summarises current knowledge of the
      epidemiology of genetic variability in hepadnaviruses and, due to rapid progress
      in the field, updates several recent reviews on HBV genotypes and subgenotypes.

PMID- 17206752
TI  - Viral and cellular determinants involved in hepadnaviral entry.
AB  - Hepadnaviridae is a family of hepatotropic DNA viruses that is divided into the
      genera orthohepadnavirus of mammals and avihepadnavirus of birds. All members of
      this family can cause acute and chronic hepatic infection, which in the case of
      human hepatitis B virus (HBV) constitutes a major global health problem. Although
      our knowledge about the molecular biology of these highly liver-specific viruses
      has profoundly increased in the last two decades, the mechanisms of attachment
      and productive entrance into the differentiated host hepatocytes are still
      enigmatic. The difficulties in studying hepadnaviral entry were primarily caused
      by the lack of easily accessible in vitro infection systems. Thus, for more than
      twenty years, differentiated primary hepatocytes from the respective species were
      the only in vitro models for both orthohepadnaviruses (e.g. HBV) and
      avihepadnaviruses (e.g. duck hepatitis B virus [DHBV]). Two important discoveries
      have been made recently regarding HBV: (1) primary hepatocytes from tree-shrews;
      i.e., Tupaia belangeri, can be substituted for primary human hepatocytes, and (2)
      a human hepatoma cell line (HepaRG) was established that gains susceptibility for
      HBV infection upon induction of differentiation in vitro. A number of potential
      HBV receptor candidates have been described in the past, but none of them have
      been confirmed to function as a receptor. For DHBV and probably all other avian
      hepadnaviruses, carboxypeptidase D (CPD) has been shown to be indispensable for
      infection, although the exact role of this molecule is still under debate. While
      still restricted to the use of primary duck hepatocytes (PDH), investigations
      performed with DHBV provided important general concepts on the first steps of
      hepadnaviral infection. However, with emerging data obtained from the new HBV
      infection systems, the hope that DHBV utilizes the same mechanism as HBV only
      partially held true. Nevertheless, both HBV and DHBV in vitro infection systems
      will help to: (1) functionally dissect the hepadnaviral entry pathways, (2)
      perform reverse genetics (e.g. test the fitness of escape mutants), (3) titrate
      and map neutralizing antibodies, (4) improve current vaccines to combat acute and
      chronic infections of hepatitis B, and (5) develop entry inhibitors for future
      clinical applications.

PMID- 17206753
TI  - Intracellular transport of hepatitis B virus.
AB  - For genome multiplication hepadnaviruses use the transcriptional machinery of the
      cell that is found within the nucleus. Thus the viral genome has to be
      transported through the cytoplasm and nuclear pore. The intracytosolic
      translocation is facilitated by the viral capsid that surrounds the genome and
      that interacts with cellular microtubules. The subsequent passage through the
      nuclear pore complexes (NPC) is mediated by the nuclear transport receptors
      importin alpha and beta. Importin alpha binds to the C-terminus of the capsid
      protein that comprises a nuclear localization signal (NLS). The exposure of the
      NLS is regulated and depends upon genome maturation and/or phosphorylation of the
      capsid protein. As for other karyophilic cargos using this pathway importin alpha
      interacts with importin beta that facilitates docking of the import complex to
      the NPC and the passage through the pore. Being a unique strategy, the import of
      the viral capsid is incomplete in that it becomes arrested inside the nuclear
      basket, which is a cage-like structure on the karyoplasmic face of the NPC.
      Presumably only this compartment provides the factors that are required for
      capsid disassembly and genome release that is restricted to those capsids
      comprising a mature viral DNA genome.

PMID- 17206754
TI  - Hepatitis B virus replication.
AB  - Hepadnaviruses, including human hepatitis B virus (HBV), replicate through
      reverse transcription of an RNA intermediate, the pregenomic RNA (pgRNA). Despite
      this kinship to retroviruses, there are fundamental differences beyond the fact
      that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation
      of reverse transcription: it occurs by protein-priming, is strictly committed to
      using an RNA hairpin on the pgRNA, epsilon, as template, and depends on cellular
      chaperones; moreover, proper replication can apparently occur only in the
      specialized environment of intact nucleocapsids. This complexity has hampered an
      in-depth mechanistic understanding. The recent successful reconstitution in the
      test tube of active replication initiation complexes from purified components,
      for duck HBV (DHBV), now allows for the analysis of the biochemistry of
      hepadnaviral replication at the molecular level. Here we review the current state
      of knowledge at all steps of the hepadnaviral genome replication cycle, with
      emphasis on new insights that turned up by the use of such cell-free systems. At
      this time, they can, unfortunately, not be complemented by three-dimensional
      structural information on the involved components. However, at least for the
      epsilon RNA element such information is emerging, raising expectations that
      combining biophysics with biochemistry and genetics will soon provide a powerful
      integrated approach for solving the many outstanding questions. The ultimate,
      though most challenging goal, will be to visualize the hepadnaviral reverse
      transcriptase in the act of synthesizing DNA, which will also have strong
      implications for drug development.

PMID- 17206755
TI  - Hepatitis B virus morphogenesis.
AB  - The hepatitis B virus (HBV) particle consists of an envelope containing three
      related surface proteins and probably lipid and an icosahedral nucleocapsid of
      approximately 30 nm diameter enclosing the viral DNA genome and DNA polymerase.
      The capsid is formed in the cytosol of the infected cell during packaging of an
      RNA pregenome replication complex by multiple copies of a 21-kDa C protein. The
      capsid gains the ability to bud during synthesis of the viral DNA genome by
      reverse transcription of the pregenome in the lumen of the particle. The three
      envelope proteins S, M, and L shape a complex transmembrane fold at the
      endoplasmic reticulum, and form disulfide-linked homo- and heterodimers. The
      transmembrane topology of a fraction of the large envelope protein L changes post
      translationally, therefore, the N terminal domain of L (preS) finally appears on
      both sides of the membrane. During budding at an intracellular membrane, a short
      linear domain in the cytosolic preS region interacts with binding sites on the
      capsid surface. The virions are subsequently secreted into the blood. In
      addition, the surface proteins can bud in the absence of capsids and form
      subviral lipoprotein particles of 20 nm diameter which are also secreted.

PMID- 17206756
TI  - Hepatitis B virus-induced oncogenesis.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers in the world
      with an annual incidence of more than 500000 in the year 2000. Its incidence is
      rising in many countries. Recently, it has been estimated that about 53% of HCC
      cases in the world are related to hepatitis B virus (HBV). The epidemiological
      association of HBV with HCC is well established. In recent studies, it was
      revealed that HBsAg carriers have a 25-37 times increased risk of developing HCC
      as compared to non-infected people. At present, HBV-associated carcinogenesis can
      be seen as a multi-factorial process that includes both direct and indirect
      mechanisms that might act synergistically. The integration of HBV DNA into the
      host genome occurs at early steps of clonal tumor expansion. The integration has
      been shown in a number of cases to affect a variety of cancer-related genes and
      to exert insertional mutagenesis. The permanent liver inflammation, induced by
      the immune response, resulting in a degeneration and regeneration process confers
      to the accumulation of critical mutations in the host genome. In addition to
      this, the regulatory proteins HBx and the PreS2 activators that can be encoded by
      the integrate exert a tumor promoter-like function resulting in positive
      selection of cells producing a functional regulatory protein. Gene expression
      profiling and proteomic techniques may help to characterize the molecular
      mechanisms driving HBV-associated carcinogenesis, and thus potentially identify
      new strategies in diagnosis and therapy.

PMID- 17206757
TI  - Pathogenesis of hepatitis B virus infection.
AB  - Infection with hepatitis B virus (HBV) leads to a wide spectrum of clinical
      presentations ranging from an asymptomatic carrier state to self-limited acute or
      fulminant hepatitis to chronic hepatitis with progression to cirrhosis and
      hepatocellular carcinoma. Infection with HBV is one of the most common viral
      diseases affecting man. Both viral factors as well as the host immune response
      have been implicated in the pathogenesis and clinical outcome of HBV infection.
      In this review, we will discuss the impact of virus-host interactions for the
      pathogenesis of HBV infection and liver disease. These interactions include the
      relevance of naturally occurring viral variants for clinical disease, the role of
      virus-induced apoptosis for HBV-induced liver cell injury and the impact of
      antiviral immune responses for outcome of infection.

PMID- 17206758
TI  - Avian hepatitis B viruses: molecular and cellular biology, phylogenesis, and host
      tropism.
AB  - The human hepatitis B virus (HBV) and the duck hepatitis B virus (DHBV) share
      several fundamental features. Both viruses have a partially double-stranded DNA
      genome that is replicated via a RNA intermediate and the coding open reading
      frames (ORFs) overlap extensively. In addition, the genomic and structural
      organization, as well as replication and biological characteristics, are very
      similar in both viruses. Most of the key features of hepadnaviral infection were
      first discovered in the DHBV model system and subsequently confirmed for HBV.
      There are, however, several differences between human HBV and DHBV. This review
      will focus on the molecular and cellular biology, evolution, and host adaptation
      of the avian hepatitis B viruses with particular emphasis on DHBV as a model
      system.

PMID- 17206761
TI  - Effects of nociceptin/orphanin FQ on rats with cathartic colon.
AB  - AIM: To demonstrate the change and effect of nociceptin/orphanin FQ in the colon
      of rats with cathartic colon. METHODS: The cathartic colon model was established
      by feeding rats rhubarb for 3 mo, the changes of colonic electromyography were
      investigated by both suspension muscle strips test and serosal recordings of
      colonic myoelectrical activity. Immunohistochemical staining (S-P methods) and
      image analysis were used to determine the changes of nociceptin/orphanin FQ in
      the proximal colon and distal colon of rats with cathartic colon. RESULTS:
      Suspension muscle strips test in vitro showed OFQ (10(-9)-10(-6) mol/L)
      concentration dependently caused an immediate tonic contraction in the isolated
      colon. But the increase of tension in cathartic colon was less than control
      groups (P < 0.01). Intravenous administration of OFQ (1 microg/kg) caused phasic
      contractions in the proximal colon, while the amplitude of phasic contractions
      caused by OFQ in cathartic colon was much lower than that in the control groups
      (2.58 +/- 0.41 vs 4.16 +/- 0.53, t = -2.6, P = 0.012). OFQ was highly expressed
      in the myenteric plexus of the rat colon but not in the muscle cells. The
      immunoreactivity of OFQ in the proximal colon in cathartic colon rats decreased
      significantly compared with the control group (P = 0.001). CONCLUSION: Colonic
      smooth muscle of cathartic colon showed low sensitivity to the stimulation of
      OFQ, suggesting that it might be caused by the abnormal distribution of OFQ or
      the abnormalities of receptors, leading to the disorganization of dynamic and
      incoordinated contractions.

PMID- 17206762
TI  - Malignancy and mortality in a population-based cohort of patients with coeliac
      disease or "gluten sensitivity".
AB  - AIM: To determine the risk of malignancy and mortality in patients with a
      positive endomysial or anti-gliadin antibody test in Northern Ireland. METHODS: A
      population-based retrospective cohort study design was used. Laboratory test
      results used in the diagnosis of coeliac disease were obtained from the Regional
      Immunology Laboratory, cancer statistics from the Northern Ireland Cancer
      Registry and mortality statistics from the General Registrar Office, Northern
      Ireland. Age standardized incidence ratios of malignant neoplasms and
      standardized mortality ratios of all-cause and cause-specific mortality were
      calculated. RESULTS: A total of 13 338 people had an endomysial antibody and/or
      an anti-gliadin antibody test in Northern Ireland between 1993 and 1996. There
      were 490 patients who tested positive for endomysial antibodies and they were
      assumed to have coeliac disease. There were 1133 patients who tested positive for
      anti-gliadin antibodies and they were defined as gluten sensitive. Malignant
      neoplasms were not significantly associated with coeliac disease; however, all
      cause mortality was significantly increased following diagnosis. The standardized
      incidence and mortality ratios for non-Hodgkin's lymphoma were increased in
      coeliac disease patients but did not reach statistical significance. Lung and
      breast cancer incidence were significantly lower and all-cause mortality,
      mortality from malignant neoplasms, non-Hodgkin's lymphoma and digestive system
      disorders were significantly higher in gluten sensitive patients compared to the
      Northern Ireland population. CONCLUSION: Patients with coeliac disease or gluten
      sensitivity had higher mortality rates than the Northern Ireland population. This
      association persists more than one year after diagnosis in patients testing
      positive for anti-gliadin antibodies. Breast cancer is significantly reduced in
      the cohort of patients with gluten sensitivity.

PMID- 17206759
TI  - The woodchuck as an animal model for pathogenesis and therapy of chronic
      hepatitis B virus infection.
AB  - This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an
      animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV)
      infection and disease in humans. The establishment of woodchuck breeding
      colonies, and use of laboratory-reared woodchucks infected with defined WHV
      inocula, have enhanced our understanding of the virology and immunology of HBV
      infection and disease pathogenesis, including major sequelae like chronic
      hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and
      of viral load on the natural history of infection and disease progression has
      been firmly established along the way. More recently, the model has shed new
      light on the role of host immune responses in these natural processes, and on how
      the immune system of the chronic carrier can be manipulated therapeutically to
      reduce or delay serious disease sequelae through induction of the recovery
      phenotype. The woodchuck is an outbred species and is not well defined
      immunologically due to a limitation of available host markers. However, the
      recent development of several key host response assays for woodchucks provides
      experimental opportunities for further mechanistic studies of outcome predictors
      in neonatal- and adult-acquired infections. Understanding the virological and
      immunological mechanisms responsible for resolution of self-limited infection,
      and for the onset and maintenance of chronic infection, will greatly facilitate
      the development of successful strategies for the therapeutic eradication of
      established chronic HBV infection. Likewise, the results of drug efficacy and
      toxicity studies in the chronic carrier woodchucks are predictive for responses
      of patients chronically infected with HBV. Therefore, chronic WHV carrier
      woodchucks provide a well-characterized mammalian model for preclinical
      evaluation of the safety and efficacy of drug candidates, experimental
      therapeutic vaccines, and immunomodulators for the treatment and prevention of
      HBV disease sequelae.

PMID- 17206760
TI  - Antiviral therapy and resistance with hepatitis B virus infection.
AB  - Hepatitis B virus (HBV) infection is still the most common cause of
      hepatocellular carcinoma and liver cirrhosis world wide. Recently, however, there
      has been quite dramatic improvement in the understanding of HBV associated liver
      disease and its treatment. It has become clear that high viral replication is a
      major risk factor for the development of both cirrhosis and hepatocellular
      carcinoma. Early studies have shown lamivudine lowers the risk of HBV associated
      complications. There are currently three nucleos(t)ides licensed, in addition to
      interferon, and there are more drugs coming to the market soon. Interferon or its
      pegylated counterpart are still the only options for treatment with defined end
      points, while nucleos(t)ides therapy is used mostly for long term treatment.
      Combination therapies have not been shown to be superior to monotherapy in naive
      patients, however, the outcome depends on how the end point is defined.
      Interferon plus lamivudine achieves a higher viral suppression than either
      treatment alone, even though Hbe-seroconversion was not different after a one
      year treatment. HBV-genotypes emerge as relevant factors, with genotypes "A" and
      "B" responding relatively well to interferon, achieving up to 20% HBsAg clearance
      in the case of genotype "A". In addition to having a defined treatment duration,
      interferon has the advantage of lacking resistance selection, which is a major
      drawback for lamivudine and the other nucleos(t)ides. The emergence of resistance
      against adefovir and entecavir is somewhat slower in naive compared to lamivudine
      resistant patients. Adefovir has a low resistance profile with 3%, 9%, 18%, and
      28% after 2, 3, 4, and 5 years, respectively, while entecavir has rarely produced
      resistance in naive patients for up to 3 years.

PMID- 17206763
TI  - Age-related histomorphologic changes in the canine gastrointestinal tract: a
      histologic and immunohistologic study.
AB  - AIM: To examine the changes in the histomorphology of the gastric, jejunal and
      colonic wall of dogs due to physiological aging. METHODS: Full thickness biopsies
      were taken from the gastrointestinal tracts of 28 dogs of different ages. The
      thickness of the different layers of the wall was measured and the numbers of
      proliferating cells as indicated by immunohistochemical detection of Ki67 were
      counted. RESULTS: In the three excision sites, the thickness of all subepithelial
      layers increased with rising age. The strongest correlation between age and
      thickness of the intestinal wall was found in the first 10 years of life and in
      the jejunum (r = 0.6-0.71 for the deep lamina propria mucosa, the muscularis
      mucosa, and the circular layer of the tunica muscularis). The number of
      proliferating cells decreased during aging, with the strongest correlation in the
      lamina propria mucosa and lamina muscularis mucosa of the jejunum and in the
      colonic submucosa (r = -0.61 to -0.71). Epithelial proliferation was only weakly
      correlated to the age. CONCLUSION: The morphology of the deeper layers and the
      proliferation of mesenchymal cells of the intestinal wall of healthy dogs are
      correlated with age. Gastrointestinal epithelial proliferation is only weakly age
      correlated.

PMID- 17206766
TI  - Recombinant human morphogenetic protein: its future role in spinal fusions.
AB  - The marriage of basic scientific research and clinical application often leads to
      profound advances in our understanding of various disease processes and how they
      may be ameliorated. One such fortuitous combination has been the discovery of
      bone morphogenetic proteins (BMPs) and their potential application in spinal
      fusions. The goal of this article is to introduce the neurosurgeon to the basic
      biology of this protein family, current experimental data (in vitro and in vivo
      models) demonstrating their effectiveness in enhancing bony fusions, and
      preliminary clinical trials utilizing BMP in long bone fusions. Using this
      information, a proposal for the use of BMP in spinal fusions under various
      clinical scenarios will be discussed.

PMID- 17206765
TI  - Intraoperative chymopapain in lumbar laminotomy for disc disease: a less invasive
      technique.
AB  - The use of chymopapain in the treatment of lumbar disc herniation has been widely
      studied since Smith first described its use in humans in 1963. The authors
      describe the use of chymopapain intraoperatively in open lumbar microdiscectomy
      in 63 patients. When combined with the results of a previous study performed at
      the same institution, the authors found that this technique significantly reduces
      the rate of recurrent disc herniation when compared with traditional laminotomy
      with discectomy. This procedure maximizes the benefits of each approach taken
      separately, allowing for decompression of the nerve root from a free fragment or
      sequestered disc and preventing recurrence through dissolution of the nucleus
      pulposus. Overall, outcome was good or excellent immediately postoperatively in
      73% of the 63 patients and in 64% at last follow-up evaluation. Additionally,
      this procedure is safe with no complications noted in the immediate perioperative
      period or at follow-up evaluation.

PMID- 17206767
TI  - Bone morphogenetic protein gene therapy for the induction of spinal arthrodesis.
AB  - Gene therapy has many potential applications in neurosurgery. One application
      involves bone morphogenetic protein-2 (BMP-2), a low-molecular-weight
      glycoprotein that induces bone formation in vivo. Numerous studies have
      demonstrated that the BMP-2 protein can enhance spinal fusion. This study was
      undertaken to determine whether direct injection of an adenoviral construct
      containing the BMP-2 gene can be used for spinal fusion. Twelve athymic nude rats
      were used in this study. Recombinant, replication-defective type-5 adenovirus
      with a universal promoter and BMP-2 gene (Ad-BMP-2) was used. A second adenovirus
      constructed with a universal promoter and beta-galactosidase (beta-gal) gene (Ad
      beta-gal) was used as a control. Seven and one-half microliters of virus was
      injected percutaneously and paraspinally at the lumbosacral junction in three
      groups (four animals each): 1) Ad-BMP-2 bilaterally, 2) Ad-BMP-2 on the right, Ad
      beta-gal on the left, and 3) Ad-beta-gal bilaterally. Computerized tomography
      (CT) scans of the lumbosacral spine were obtained at 3, 5, and 12 weeks. At 12
      weeks, the animals were killed for histological inspection. Ectopic bone
      formation was seen both on three-dimensional CT reconstruction and histologically
      in all rats at sites treated with Ad-BMP-2. Histological analysis revealed bone
      at different stages of maturity adjacent to the spinous processes, laminae, and
      transverse processes. This study clearly demonstrated that it is possible to
      produce in vivo endochondral bone formation by using direct adenoviral construct
      injection into the paraspinal musculature, which suggests that gene therapy may
      be useful for spinal fusion in the future.

PMID- 17206768
TI  - Posterolateral approach for decompression with anterior and posterior fusion: a
      less invasive surgical technique for stabilization of the thoracic spine. Case
      report.
AB  - The goals of surgery in unstable thoracic fractures or tumors involving the
      thoracic spine are neural decompression, correction of deformity, and
      stabilization. Several different approaches can be used to achieve these goals.
      The anterior, combined anterior and posterior, and more recently thoracoscopic
      approaches are well described in the literature and are extremely effective in
      achieving the goals mentioned. However, they do carry with them significant
      morbidity and mortality rates in patients who are elderly, who have associated
      medical problems, or for whom there are contraindications to thoracic surgery.
      The authors believe the posterolateral approach is a viable alternative that is
      reasonably well tolerated in this select patient population. One can achieve
      circumferential neural decompression as well as anterior and posterior
      arthrodesis through a single incision. Most neurosurgeons are familiar with the
      anatomical landmarks and technical steps in the posterolateral approach, and the
      authors believe it is a less invasive method that can be especially useful and
      should not be overlooked in this subgroup of patients.

PMID- 17206769
TI  - Thoracoscopic sympathectomy: techniques and outcomes.
AB  - Thoracic sympathectomy is an important option in the treatment of palmar
      hyperhidrosis and pain disorders. Earlier surgical procedures were highly
      invasive with known morbidity, acceptable outcome, and established recurrence
      rates that were the limitations to considering surgical treatment. Thoracoscopic
      sympathectomy is a minimally invasive procedure that allows detailed
      visualization of the sympathetic ganglia and minimal postoperative morbidity;
      however, outcome studies of this technique have been limited. The authors treated
      39 patients with 60 thoracoscopic procedures, and the outcomes in this small
      series were equivalent to previously established open surgical techniques;
      however, operative moribidity rates, hospital stay, and time of return to normal
      activity were substantially reduced. Complications and recurrence of symptoms
      were also comparable to previous reports. Overall patient satisfaction and
      willingness to repeat the operative procedure ranged from 66 to 96% in all
      patients. Patients and physicians can consider minimally invasive thoracoscopic
      sympathectomy procedures as an option to treat sympathetically mediated disorders
      because of the procedure's reduced morbidity and at least equivalent outcome
      rates in comparison to other treatments.

PMID- 17206770
TI  - Endoscopic microscopic transpedicular thoracic discectomy. Technical note.
AB  - In an effort to make thoracic discectomy simple and less invasive while using
      direct visualization, a 70 degrees -angled lens endoscope has been adopted to
      visualize the ventral aspect of the spinal cord dura mater during microsurgical
      thoracic discectomy via a transpedicular approach. The patient is positioned in a
      60 degrees forwardly inclined lateral position with the side of the lesion facing
      upward. After radiographic corroboration of the correct level, a transpedicular
      approach is made using a 1.5-cm-diameter tubular retractor through a 2-cm-long
      paramedian transverse skin incision. With the aid of an operating microscope, the
      ipsilateral facet joint, including the upper portion of the pedicle, is removed
      using a high-speed drill, thus exposing the neural foramen, intervertebral disc,
      and upper portion of the pedicle leading to the vertebral bodies. When the
      herniated disc and bone spur have been removed laterally in relation to the
      spinal cord, creating a cavity under the operating microscope, a 4-mm-diameter
      rigid endoscope with a 70 degrees -angled lens is mounted to an endoscope holder
      so that the ventral aspect of the spinal cord dura mater can be visualized
      directly. With the aid of direct endoscopic visualization, the disc and bone
      spur, which compress the spinal cord anteriorly, are pushed away toward a cavity
      created at the intervertebral space and are removed using a downward-biting long
      armed curette. Patients with myelopathy are kept overnight in the hospital;
      however, those with radiculopathy are discharged home on the same day as their
      operation. The surgical technique and two illustrative cases are reported.

PMID- 17206771
TI  - Minimally invasive techniques in spinal surgery: current practice.
AB  - Minimally invasive spinal surgery under arthroscopic or endoscopic magnification
      and illumination is emerging as an alternative, reliable method of treatment in a
      variety of spinal disorders. The operative techniques being used for discectomy
      and retrieval of herniated disc fragments or stabilization of unstable spinal
      motion segments are being utilized for visual diagnosis and debridement of
      infectious discitis and osteomyelitis transpedicular and transforaminal vertebral
      body biopsy, temporary diagnostic fixation of unstable lumbar motion segments,
      and transforaminal epidural steroid therapy.

PMID- 17206772
TI  - Percutaneous lumbar discectomy with a working endoscope and laser assistance.
AB  - The authors describe percutaneous disc surgery performed via the unilateral
      monoportal method with a C-arm image intensifier, a working endoscope, and an
      yttrium-aluminum-garnet laser in 300 patients at three community hospitals over a
      6-year period. Visualizing the area of the annulus to be fenestrated, verifying
      the status of the nerve root, inspecting the cavity created, and monitoring laser
      hemostasis and vaporization all contributed to patient safety. Fewer than 2% of
      the cases required a second surgery. The only postoperative sequelae recorded
      were one psoas hematoma, which resolved, and sympathetic mediated pain in 5% of
      the patients who responded to appropriate treatment. For treatment of a prolapsed
      lumbar disc, a 1-hour endoscopic procedure performed while the patient receives a
      neuroleptanalgesic continues to be a significant surgical alternative.

PMID- 17206773
TI  - Comparison of functional outcomes from orthopedic and neurosurgical interventions
      in spastic diplegia.
AB  - Selective dorsal rhizotomy (SDR) and orthopedic surgery, in the form of muscle
      tendon (MT) lengthening surgery are commonly performed in ambulatory children
      with spastic diplegia to improve their level of motor function. This
      investigation is a post hoc comparison of the functional effects from each of
      these surgical options in 30 patients with spastic diplegia who underwent one of
      these interventions as their initial surgical procedure. Sixteen children
      underwent SDR and 14 underwent MT surgery in two separate prospective clinical
      trials. The same functional outcome measures preoperatively and approximately 1
      year postoperatively were used in both studies including temporospatial
      parameters from three-dimensional gait analysis, the total score, and score on
      each of the five dimensions of the Gross Motor Function Measure (GMFM).
      Comparisons indicate that patients who underwent SDR had significant improvements
      in GMFM Dimensions 2, 4, and 5 as well as in total score, although 63% of those
      studied had a 10% or more reduction in gait velocity. Gait was more predictably
      improved in the MT group, with only 21% demonstrating reductions in velocity.
      Conversely, the change in GMFM scores in the MT group was not as pervasive and
      skewed toward higher skills with only GMFM Dimension 5 and total score improved
      significantly. Several important hypotheses are derived from these comparisons.
      Multicenter clinical trials are needed to define more clearly the indications for
      and to assess more comprehensively the outcomes from each intervention.

PMID- 17206774
TI  - Spasticity and strength changes as a function of selective dorsal rhizotomy.
AB  - This investigation quantified pre- and postsurgery (8 months) hamstring muscle
      spasticity and strength in children with cerebral palsy (CP) undergoing a
      selective dorsal rhizotomy. Nineteen children with CP (CP group) and six children
      with able bodies (AB group) underwent testing with a dynamometer. For the
      spasticity measure, the dynamometer measured the resistive torque of the
      hamstring muscles during passive knee extension at four different speeds. Torque
      angle data were processed to calculate the work done by the machine to extend the
      knee for each speed. Linear regression was used to calculate the slope of the
      line of best fit for the work velocity data. The slope simultaneously encompassed
      three key elements associated with spasticity (velocity, resistance, and stretch)
      and was considered the measure of spasticity. For the strength test, the
      dynamometer moved the leg from full knee extension to flexion while a maximum
      concentric contraction of the hamstring muscles was performed. Torque angle data
      were processed to calculate the work done on the machine by the child. Hamstring
      spasticity values for the CP group were significantly greater than similar values
      for AB group prior to surgery; however they were not significantly different
      after surgery. Hamstring strength values for the CP group remained significantly
      less than those for the AB group after surgery, but were significantly increased
      relative to their presurgery values. The results of spasticity testing in the
      present investigation agreed with previous studies indicating a reduction in
      spasticity for the CP group. The results of strength testing did not agree with
      those in the previous literature; a significant increase in strength was observed
      for the CP group.

PMID- 17206775
TI  - The descriptive epidemiology of craniopharyngioma.
AB  - The incidence of craniopharyngioma in the United States was estimated from two
      population-based cancer registries that include brain tumors of benign and
      borderline malignancy: the Central Brain Tumor Registry of the United States
      (CBTRUS) and Los Angeles county. Information on additional pediatric tumors was
      available from the Greater Delaware Valley Pediatric Tumor Registry (GDVPTR). The
      overall incidence of craniopharyngioma was 0.13 per 100,000 person years and did
      not vary by gender or race. A bimodal distribution by age was noted with peak
      incidence rates in children (aged 5-14 years) and among older adults (aged 65-74
      years in CBTRUS and 50-74 years in Los Angeles county). Survival information was
      available from GDVPTR and the National Cancer Data Base (NCDB), a hospital-based
      reporting system. In the NCDB, the 5-year survival rate was 80% and decreased
      with older age at diagnosis. Survival is higher among children and has improved
      in recent years. Approximately 338 cases of craniopharyngiomas are expected to
      occur annually in the United States, with 96 occurring in children from 0 to 14
      years of age.

PMID- 17206776
TI  - Recent results of primary transnasal surgery for infradiaphragmatic
      craniopharyngioma.
AB  - Results of primary transnasal surgery were evaluated in 35 patients (18 males and
      17 females) with intrasellar and suprasellar craniopharyngiomas treated between
      1985 and 1996 when more refined surgical and diagnostic techniques were
      available. Patients ranged in age from 8 to 72 years (mean 27 years); 14 patients
      were younger than 18 years of age. The transnasal approach was chosen because of
      sellar enlargement and presence of infradiaphragmatic tumor. The paramedian
      portion of the normal pituitary gland was incised vertically to reach a dorsally
      located tumor in 25 patients. Complete tumor resection was achieved in 15
      patients and subtotal removal in 19; in one patient, only aspiration of cyst
      contents was performed. Tumor regrowth was seen in three patients after subtotal
      removal; in two, total tumor removal was achieved by a second transnasal surgery,
      whereas radiotherapy was administered in the other. In a single patient, total
      tumor removal was achieved by a second transcranial surgery after cyst
      aspiration. The duration of the clinical follow-up period was at least 1 year.
      Persistent diabetes insipidus appeared after total tumor resection in five
      patients. Cerebrospinal fluid leakage occurred in three patients, with two
      requiring revision. Among 29 patients with preoperatively normal pituitary
      functions, 20 (69%) were preserved after primary total resection, whereas six
      (19.4%) of 31 previously disturbed functions were normalized. After subtotal
      removal including cyst aspiration, 39 (88.6%) of 44 normal functions were
      preserved, whereas nine (24.3%) of 37 disturbed functions were normalized. The
      transnasal approach should be the first choice in infradiaphragmatic
      craniopharyngiomas with sellar enlargement in cases in which the extrasellar
      portion is mostly cystic and is accessible. The concept of subtotal removal with
      preservation of pituitary functions, especially when treating craniopharyngioma
      in children, seems to be justified.

PMID- 17206777
TI  - Optimization of the operative corridor for the resection of craniopharyngiomas in
      children: the combined frontoorbitozygomatic temporopolar approach. Technical
      note.
AB  - Complete extirpation of tumor remains the primary goal of neurosurgeons in
      treating intracranial craniopharyngiomas. The intimate relationship of these
      lesions with the structures of the skull base and the difficulties of obtaining
      adequate operative visualization often make total removal an elusive goal. The
      authors describe the use of a combined fronto-orbitozygomatic temporopolar
      craniotomy to maximize the operative corridor and thereby increase the
      probability of maximum tumor resection without morbidity and mortality. They
      applied this approach in four children with craniopharyngiomas that involved the
      sellar and parasellar, third ventricle, cavernous sinus, and interpeduncular
      fossa regions. The surgical results are summarized with a presentation of pre-
      and postoperative imaging from two illustrative cases. A detailed description of
      the operative procedure is provided with a comparison to other previously
      described surgical approaches.

PMID- 17206778
TI  - Treatment of cystic craniopharyngiomas with yttrium-90 colloid solution.
AB  - The authors analyzed long-term follow-up data to assess the value of
      intracavitary irradiation with stereotactically implanted beta-emitting
      radioisotope (90)Y-silicate colloid for the treatment of craniopharyngiomas.
      Fifty-seven craniopharyngiomas in 42 patients were selected for retrospective
      analysis. The yttrium-90 was implanted intracavitally, using computerized
      tomography-guided and three-dimensional stereotactic treatment planning. The
      cumulative dose aimed at the inner surface of the cyst wall was 300 Gy. An
      average of 75% shrinkage of the initial cyst volume was observed. In 18 cases the
      reduction was more than 91%, and the cyst disappeared totally in 11 cases. A 50%
      decrease in cyst volume was usually apparent between the 2nd and 4th months. A
      70% decrease in cyst volume was seen by the 5th and 6th months and an 80%
      reduction by the 7th and 8th months. Cysts that were unchanged remained so
      throughout the observation period. The time course of volume reduction could be
      expressed mathematically by the formula of 0.73 X e(-0.62 X T) + 0.27, where "e"
      is the basic number of natural logarithm and "T" is the time expressed in months.
      Mean survival duration after intracavitary irradiation was 9.4 years. The
      shrinkage of the cyst was a consequence of fibrosis of the wall, as seen on
      histopathological examination. The neuroophthalmological prognosis was favorable
      only when the optic disc was normal or nearly normal at the time of the
      treatment. In the presence of preexisting optic atrophy, visual deterioration
      proved to be irreversible. The long-term results support the view that
      intracavitary (90)Y-irradiation is a noninvasive and very effective method of
      treatment for craniopharyngioma cysts. Because of the 1.1 mm half-life decay of
      beta irradiation, it cannot influence the solid part of the tumor; therefore, the
      best result can be expected in solitary cysts.

PMID- 17206779
TI  - Transfection of C6 glioma cells with the bax gene and increased sensitivity to
      treatment with cytosine arabinoside.
AB  - Genes known to be involved in the regulation of apoptosis include members of the
      bcl-2 gene family, such as inhibitors of apoptosis (bcl-2 and bcl-xl) and
      promotors of apoptosis (bax). The authors investigated a potential approach for
      the treatment of malignant gliomas by using a gene transfection technique to
      manipulate the level of an intracellular protein involved in the control of
      apoptosis. The authors transfected the murine bax gene, which had been cloned
      into a mammalian expression vector, into the C6 rat glioma cell line.
      Overexpression of the bax gene resulted in a decreased growth rate (average
      doubling time of 32.96 hours compared with 22.49 hours for untransfected C6, and
      23.11 hours for clones transfected with pcDNA3 only), which may be caused, in
      part, by an increased rate of spontaneous apoptosis (0.77 +/- 0.15% compared with
      0.42 +/- 0.08% for the vector-only transfected C6 cell line; p = 0.038, two
      tailed Student's t-test). Treatment with 1 microM of cytosine arabinoside (ara-C)
      resulted in significantly more cells undergoing apoptosis in the cell line
      overexpressing bax than in the vector-only control cell line (23.57 +/- 2.6%
      compared with 5.3 +/- 0.7% terminal deoxynucleotidyl transferase--mediated
      biotinylated--deoxyuridine triphosphate nick-end labeling technique-positive
      cells; p = 0.007). Furthermore, measurements of growth curves obtained
      immediately after treatment with 0.5 microM ara-C demonstrated a prolonged growth
      arrest of at least 6 days in the cell line overexpressing bax. These results can
      be used collectively to argue that overexpression of bax results in increased
      sensitivity of C6 cells to ara-C and that increasing bax expression may be a
      useful strategy, in general, for increasing the sensitivity of gliomas to
      antineoplastic treatments.

PMID- 17206780
TI  - Distribution and stability of antisense phosphorothioate oligonucleotides in
      rodent brain following direct intraparenchymal controlled-rate infusion.
AB  - High-flow microinfusion is a novel technique for delivery of compounds directly
      into the brain parenchyma, bypassing the blood-brain barrier. The feasibility of
      this technique has been demonstrated with low-molecular-weight compounds,
      macromolecular dyes, and proteins. Delivery of antisense oligonucleotides into
      the brain parenchyma represents an additional potential application of this
      technique not previously described. In this report, the authors examined the
      distribution and disposition of phosphorothioate oligodeoxynucleotide (PS-ODN)
      infused for this reason. An 18-mer (35)S-PS-ODN (molecular weight approximately
      6000) was infused over 1 hour into the caudate putamen of Fischer 344 rats. At 1,
      6, 12, 24, and 48 hours after beginning the infusion, the brains were extracted
      and analyzed using quantitative autoradiographic techniques. Cerebrospinal fluid
      (CSF) was also aspirated from the cisterna magna and analyzed for radioactivity
      and stability of the (35)S-PS-ODN. At 1 hour, the infused ODN was uniformly
      distributed in brain tissue, with a maximum average concentration of 4806.5 +/-
      210.5 nCi/g. This represents a tissue concentration of 19.2 +/- 0.84 microM.
      Extensive spread into surrounding parenchyma was observed over the ensuing 47
      hours. The (35)S-PS-ODN radioactivity peaked in the CSF at the end of the 1-hour
      infusion, containing 10% (50 +/- 20 nCi) of the infused radioactivity. Activity
      then decayed exponentially over 11 hours, stabilizing at a lower CSF content of
      0.2% (1 +/- 0.1 nCi). The volume of distribution (V(d)) was 105 +/- 7.9 mm3 at 1
      hour, representing a ratio of V(d)/V(i) (volume of infusion) of 5.2. The V(d)
      increased to 443.4 +/- 62.3 mm(3) at the end of 48 hours, whereas the average
      minimum tissue concentration decreased from 15.2 to 3.2 microM. Undegraded 18-mer
      was seen throughout the 48-hour period using 20% polyacrylamide/7M urea gel
      electrophoresis. The animals tolerated the infusion without evidence of toxicity,
      and minimal structural changes in tissue were observed on histological
      examination. Thus, PS-ODN can be safely delivered in high concentrations to wide
      areas of the rat brain by using high-flow microinfusion, and the concentrations
      remain stable even after 48 hours in situ.

PMID- 17206781
TI  - The future prospects of microbial cellulose in biomedical applications.
AB  - Microbial cellulose has proven to be a remarkably versatile biomaterial and can
      be used in wide variety of applied scientific endeavors, such as paper products,
      electronics, acoustics, and biomedical devices. In fact, biomedical devices
      recently have gained a significant amount of attention because of an increased
      interest in tissue-engineered products for both wound care and the regeneration
      of damaged or diseased organs. Due to its unique nanostructure and properties,
      microbial cellulose is a natural candidate for numerous medical and tissue
      engineered applications. For example, a microbial cellulose membrane has been
      successfully used as a wound-healing device for severely damaged skin and as a
      small-diameter blood vessel replacement. The nonwoven ribbons of microbial
      cellulose microfibrils closely resemble the structure of native extracellular
      matrices, suggesting that it could function as a scaffold for the production of
      many tissue-engineered constructs. In addition, microbial cellulose membranes,
      having a unique nanostructure, could have many other uses in wound healing and
      regenerative medicine, such as guided tissue regeneration (GTR), periodontal
      treatments, or as a replacement for dura mater (a membrane that surrounds brain
      tissue). In effect, microbial cellulose could function as a scaffold material for
      the regeneration of a wide variety of tissues, showing that it could eventually
      become an excellent platform technology for medicine. If microbial cellulose can
      be successfully mass produced, it will eventually become a vital biomaterial and
      will be used in the creation of a wide variety of medical devices and consumer
      products.

PMID- 17206782
TI  - Dendrimer-based targeted delivery of an apoptotic sensor in cancer cells.
AB  - Our previous studies have demonstrated the applicability of poly(amidoamine)
      (PAMAM) dendrimers as a platform for the targeted delivery of chemotherapeutic
      drugs both in vitro and in vivo. To monitor the rate and extent of cell-killing
      caused by the delivered chemotherapeutic drug, we wished to analyze the degree of
      apoptosis in targeted cells on a real-time basis. As the apoptosis-regulating
      caspases are activated during the apoptotic process, several caspase
      hydrolyzable, fluorescence resonance energy transfer (FRET)-based substrates have
      been marketed for the detection of apoptosis. However, the applicability of these
      agents is limited because of their nonspecificity and the consequent high
      background fluorescence in tissues. Here we show the synthesis, characterization,
      and in vitro targeting of an engineered PAMAM nanodevice in which folic acid (FA)
      is conjugated as the targeting molecule and a caspase-specific FRET-based agent
      (PhiPhiLux G1D2) is conjugated as the apoptosis-detecting agent. This conjugate
      specifically targets FA-receptor-positive, KB cells. In these cells, the
      apoptosis-inducing agent staurosporine caused a 5-fold increase in the cellular
      fluorescence. These results show, for the first time, the potential applicability
      of a targeted apoptosis-measuring nanodevice, which could be used for
      simultaneously monitoring the apoptotic potential of a delivered drug.

PMID- 17206783
TI  - Synergistic activity of hydrophilic modification in antibiotic polymers.
AB  - Quaternized poly(vinylpyridine) is known to kill up to 99% of drug-resistant gram
      positive and -negative bacteria but shows minimal biocompatibility. We report
      enhanced bactericidal activity of vinylpyridine through copolymerization with
      hydroxyethyl methacrylate and poly(ethylene gycol) methyl ether methacrylate.
      Copolymers with increasing comonomer content were synthesized by radical
      polymerization and quaternized with hexylbromide. We assessed the effects of the
      changes in polymer composition on the bactericidal activity of the surface
      activity using a bioluminescent pathogenic strain of Escherichia coli (O157:H7).
      By recording the photoluminescence emitted by these bacteria in contact with the
      copolymers, it was shown that several of the copolymers possess better
      antibacterial efficiency than quaternized poly(vinylpyridine). Results indicate
      that several of the copolymers synthesized possess antibacterial activity
      approximately 20 times greater than the pure quaternized poly(vinylpyridine)
      homopolymer, while only containing 1 wt % hexylated pyridinium. This behavior is
      explained by the increased surface wettability of the copolymers containing
      lesser amounts of poly(vinylpyridine), as bactericidal behavior correlates to the
      hydrophilicity of the system as measured by contact angles. A hydrophilicity
      based design-paradigm can significantly improve both the efficacy and the
      biocompatibility of antibacterial materials.

PMID- 17206784
TI  - Plasmid DNA adsorption on silica: kinetics and conformational changes in
      monovalent and divalent salts.
AB  - A quartz crystal microbalance with dissipation (QCM-D) is used to determine the
      adsorption rate of a supercoiled plasmid DNA onto a quartz surface and the
      structure of the resulting adsorbed DNA layer. To better understand the DNA
      adsorption mechanisms and the adsorbed layer physicochemical properties, the QCM
      D data are complemented by dynamic light scattering measurements of diffusion
      coefficients of the DNA molecules as a function of solution ionic composition.
      The data from simultaneous monitoring of variations in frequency and dissipation
      energy with the QCM-D suggest that the adsorbed DNA layer is more rigid in the
      presence of divalent (calcium) cations compared to monovalent (sodium) cations.
      Adsorption rates are significantly higher in the presence of calcium, attaining a
      transport-limited rate at about 1 mM Ca2+. Results further suggest that in low
      ionic strength solutions containing 1 mM Ca2+ and in moderately high ionic
      strength solutions containing 300 mM NaCl, plasmid DNA adsorption to negatively
      charged mineral surfaces is irreversible.

PMID- 17206785
TI  - Structurally colored thin films of Ca2+-cross-linked alginate.
AB  - Alginate, or alginic acid, is an unbranched binary copolymer of (1-->4)-linked
      beta-D-mannuronic acid and alpha-L-guluronic acid. Alginate readily forms binding
      interactions with a variety of divalent metal ions, such as calcium. This binding
      has been used to cross-link bulk alginates for a wide variety of applications,
      particularly in areas of tissue engineering, medical devices, and wound-healing
      dressings. A new method is identified here for producing Ca2+-cross-linked thin
      films of sodium alginate, using an aerosolized spray of CaCl2 solution. These
      thin films exhibit structural color that varies with film thickness. It is
      demonstrated that this structural color is highly reproducible and can also be
      tuned to produce a wide range of colored films. The noted ability of alginates to
      bind metal ions is used in combination with the structural coloration afforded by
      the thin film structure as a basis for color-based optical sensing of metal ions
      in aqueous solutions. Changes in film thickness, refractive index, and
      reflectivity in response to metal ions have been measured and reported. For
      certain ions such as Cr(III) and Cr(VI), changes in film thickness are the
      predominate factors in shifting the reflected film color. In the case of other
      ions such as Pb(II), a change in film refractive index plays a significant role
      in the reflectance properties of films.

PMID- 17206786
TI  - Synthetic biomimetic hydrogels incorporated with ephrin-A1 for therapeutic
      angiogenesis.
AB  - Eph receptors and ephrin ligands are essential for vascular development and
      angiogenic remodeling. In this work, we developed biomimetic poly(ethylene
      glycol)-diacrylate hydrogels incorporated with ephrin-A1 and examined their
      angiogenic properties. Ephrin-A1 was covalently immobilized on the surface of
      hydrogels by chemical modification and photopolymerization. Ephrin-A1 immobilized
      on hydrogels was found to retain its capacity to stimulate endothelial cell
      adhesion in a dose-dependent manner as similar findings were observed on
      polystyrene culture wells pre-adsorbed with ephrin-A1. Cell adhesion stimulated
      by ephrin-A1 was abolished by treatment with soluble RGDS and anti-alpha(v)beta3
      integrin but not anti-alpha(v)beta5 integrin antibodies, suggesting that ephrin
      A1 activates cell adhesion through alpha(v)beta3 integrins. Also, surface
      immobilized ephrin-A1 was found to induce endothelial tubule formation with
      luminal diameters ranging 5-30 microm on hydrogels. The results of these studies
      demonstrate that pro-angiogenic properties of ephrin-A1 are preserved in
      hydrogels and suggest potential applications of this hydrogel system in
      regenerative medicine and tissue engineering.

PMID- 17206787
TI  - Synthesis and characterization of the novel transfection reagent poly(amino ester
      glycol urethane).
AB  - Poly(ester urethane) (PEU) is a class of biodegradable polymer that has been
      applied as tissue-engineering scaffolds with minimum toxicity. Despite its unique
      biocompatibility, there have been no reports in modifying the PEU backbone to
      design a soluble, PEU-based DNA carrier. We have developed a method of
      incorporating tertiary amines and poly(ethylene glycol) (PEG) into PEU to
      synthesize a soluble poly(amino ester glycol urethane) (PaEGU) as a novel
      transfection reagent. Parallel to this, we have synthesized poly(amino ester)
      (PaE) and poly(amino ester urethane) (PaEU) as the control polymers. The test
      transfection reagent PaEGU and the control PaE were similar in their properties
      of being soluble and buffering pH in water and their capabilities of self
      assembling with DNA and transfecting the target cells. Significantly, PaEGU
      exhibited faster hydrolysis kinetics than PaE, half-lives of 19 and 36 h for
      PaEGU and PaE, respectively, underlying PaEGU's unique property of low
      cytotoxicity. However, in comparison to PaEGU, the other control polymer, PaEU,
      was not readily dissolved in water, indicating the importance of PEG units in
      PaEGU in increasing polymer hydrophilicity. This study demonstrated a useful
      synthesis scheme for the PEU-based transfection reagent PaEGU. The combination of
      tertiary amine, ester, PEG, and urethane units in the polymer backbone
      constitutes a feasible approach for the future design of low-toxicity gene
      transfer vectors.

PMID- 17206788
TI  - Hydrogen bonding versus ion pairing in polyelectrolyte multilayers with
      homopolynucleotides.
AB  - Homopolynucleotides--poly(adenylic acid), poly(A), and poly(uridylic acid),
      poly(U)--were assembled, layer-by-layer, into thin films with poly(ethylenimine),
      PEI. Various combinations and sequences of polynucleotide and PEI were used to
      highlight contributions of electrostatic versus hydrogen bonding as driving
      forces for multilayer build-up. Assembly of alternating poly(A) and poly(U)
      failed to yield growing films, due to excessively strong interactions between
      these complimentary strands. The surface morphology of multilayers depended on
      the deposition order and whether films had been annealed by salt. Films assembled
      from preformed A/U duplexes (having high persistence lengths) were very smooth.
      Individual adsorption steps, followed by optical waveguide light-mode
      spectroscopy, showed that only complementary polynucleotides adsorb by H-bonding
      to the surface of a growing multilayer. In contrast to behavior usually observed
      for polyelectrolyte multilayer build-up, the films decreased in thickness with
      increasing salt concentration.

PMID- 17206789
TI  - Human saliva forms a complex film structure on alumina surfaces.
AB  - Films formed from saliva on surfaces are important for the maintenance of oral
      health and integrity by protection against chemical and/or biological agents. The
      aim of the present study was to investigate adsorbed amounts, thickness, and
      structure of films formed from human whole saliva on alumina surfaces by means of
      in situ ellipsometry, neutron reflectivity, and atomic force microscopy. Alumina
      (Al2O3, synthetic sapphire) is a relevant and interesting substrate for saliva
      adsorption studies as it has an isoelectric point close to that of tooth enamel.
      The results showed that saliva adsorbs rapidly on alumina. The film could be
      modeled in two layers: an inner and dense thin region that forms a uniform layer
      and an outer, more diffuse and thicker region that protrudes toward the bulk of
      the solution. The film morphology described a uniformly covering dense layer and
      a second outer layer containing polydisperse adsorbed macromolecules or
      aggregates.

PMID- 17206790
TI  - Polymer manipulation and nanofabrication in real time using transmission electron
      microscopy.
AB  - Here we present time-resolved in situ transmission electron microscopy (TEM)
      observations and real-time manipulation of nematic ordered cellulose and
      ultradrawn polyethylene films. Drawn films of these two polymers exhibited a
      unique response to the low-dose electron beam. Electron beam damage was minimal
      based on retention of an organized electron diffraction pattern. Increased
      electron dosage appeared to melt the polymer with subsequent movement and
      attraction toward preferred electron concentrations within the beam. This
      discovery allowed the preferential, directed manipulation of polymer chain
      aggregates in two dimensions. These findings provide a basis for a new technique
      to manipulate and simultaneously observe dynamic assembly at the molecular level
      of structures using TEM.

PMID- 17206791
TI  - Beta-lactoglobulin fibers under capillary flow.
AB  - We describe the capillary flow behavior of gels of beta-lactoglobulin (beta-lg)
      containing droplets of fibrils and the shear flow alignment of beta-lg fibers in
      dilute aqueous solutions. Polarized optical microscopy and laser scanning
      confocal microscopy are used to show that capillary shear flow does not affect
      the fibril droplet sizes in the beta-lg gels, the system behaving in this respect
      as a solution of compact colloidal particles under shear flow. Small-angle X-ray
      scattering (SAXS) on dilute aqueous solutions indicates that the fibers can be
      initially aligned under capillary shear, but this alignment is lost after 18 min
      of shear. Transmission electron microscopy experiments on the samples studied by
      SAXS suggest that the loss of orientation is due to a shear-induced breakup of
      the swollen fibril network. Dynamic and static light scattering on dilute beta-lg
      fibril aqueous solutions are used to show that before shear beta-lg fibrils
      behave as strongly interacting semiflexible polymers, while they behave as weakly
      interacting rods after 18 min of capillary shear.

PMID- 17206792
TI  - Self-gelling primaquine-gum arabic conjugate: an injectable controlled delivery
      system for primaquine.
AB  - Primaquine, an 8-aminoquinoline, forms a cross-linked gel with periodate-oxidized
      gum arabic rapidly by simply mixing the drug with the oxidized polysaccharide due
      to Schiff's base formation between the two amino groups of primaquine and the
      aldehyde groups in the oxidized polysaccharide. The speed of gelation is
      determined by the degree of oxidation of polysaccharide, its quantity, and the
      drug payload. Estimation of the cross-linking density of the gels showed that the
      higher is the degree of oxidation of gum arabic, the higher is the cross-linking
      density. In vitro release of primaquine into phosphate buffered saline (PBS) at
      37 degrees C demonstrated that the extent of release depended on the cross
      linking density and drug payload. Repeated extraction using PBS soon after gel
      formation showed that not all of the primaquine was conjugated to the
      polysaccharide and the release seen in vitro was mostly from the unconjugated
      drug especially from matrices with higher cross-linking density. The gels were
      found to degrade in PBS, the kinetics of degradation being dependent on the cross
      linking density. Cytotoxicity evaluation using MTT assay against L929 mouse
      fibroblasts showed that oxidized gum arabic having a degree of oxidation of 50%
      was only very mildly cytotoxic at a concentration of 0.025 g/mL. An injectable,
      biodegradable drug depot with controlled release of primaquine over several days
      or weeks would be advantageous for long-term delivery of this drug against
      malaria or leishmaniasis, and the present study shows that a primaquine-polymer
      conjugate that can be formed in situ could be an interesting possibility.

PMID- 17206793
TI  - Analysis of the surfaces of wood tissues and pulp fibers using carbohydrate
      binding modules specific for crystalline cellulose and mannan.
AB  - Carbohydrate binding modules (CBMs) are noncatalytic substrate binding domains of
      many enzymes involved in carbohydrate metabolism. Here we used fluorescent
      labeled recombinant CBMs specific for crystalline cellulose (CBM1(HjCel7A)) and
      mannans (CBM27(TmMan5) and CBM35(CjMan5C)) to analyze the complex surfaces of
      wood tissues and pulp fibers. The crystalline cellulose CBM1(HjCel7A) was found
      as a reliable marker of both bacterially produced and plant G-layer cellulose,
      and labeling of spruce pulp fibers with CBM1(HjCel7A) revealed a signal that
      increased with degree of fiber damage. The mannan-specific CBM27(TmMan5) and
      CBM35(CjMan5C) CBMs were found to be more specific reagents than a monoclonal
      antibody specific for (1-->4)-beta-mannan/galacto-(1-->4)-beta-mannan for mapping
      carbohydrates on native substrates. We have developed a quantitative fluorometric
      method for analysis of crystalline cellulose accumulation on fiber surfaces and
      shown a quantitative difference in crystalline cellulose binding sites in
      differently processed pulp fibers. Our results indicated that CBMs provide
      useful, novel tools for monitoring changes in carbohydrate content of nonuniform
      substrate surfaces, for example, during wood or pulping processes and possibly
      fiber biosynthesis.

PMID- 17206794
TI  - Synthesis of temperature-responsive heterobifunctional block copolymers of
      poly(ethylene glycol) and poly(N-isopropylacrylamide).
AB  - Heterobifunctional block copolymers of poly(ethylene glycol) (PEG) and poly(N
      isopropylacrylamide) (PNIPAM) were synthesized by reversible addition
      fragmentation chain transfer (RAFT) polymerization of NIPAM using a
      macromolecular trithiocarbonate PEG-based chain transfer agent. The
      polymerization showed all the expected features of living radical polymerization
      and allowed the synthesis of copolymers with different lengths of the PNIPAM
      block. The synthesized block copolymers contained a carboxylic acid group from L
      lysine at the focal point and a trithiocarbonate group at the terminus of the
      PNIPAM block. The trithiocarbonate functionality was converted into a thiol group
      and used for conjugation of biotin to the end of the PNIPAM block. The copolymers
      exhibited temperature-dependent association behavior in aqueous solution with a
      phase transition of approximately 32 degrees C. The described heterobifunctional
      block copolymers show promise for surface modifications with the potential for
      stimulus-controlled surface presentation of ligands attached to the terminus of
      the PNIPAM block.

PMID- 17206795
TI  - Conformational changes and aggregation of alginic acid as determined by
      fluorescence correlation spectroscopy.
AB  - Insight into the conformations and aggregation of alginic acid was gained by
      measuring its diffusion coefficient at very dilute concentrations using
      fluorescence correlation spectroscopy. Both the pH and ionic strength (I) had an
      important influence on the diffusion coefficient of the polysaccharide. For pH,
      three effects were isolated: (i) below pH 4, the charge density decreased causing
      increased aggregation; (ii) between pH 4 and 8, a molecular expansion was
      observed with increasing pH, whereas (iii) above pH 8 some dissociation of the
      polymer was observed. Increasing I from 0.001 to 0.1 M resulted in a ca. 20%
      increase in the diffusion coefficient. By coupling these measurements to molar
      mass determinations obtained by size exclusion chromatography and monomer size
      estimations determined from ab initio calculations, it was possible to determine
      the radii of gyration via de Gennes renormalization theory. From diffusion
      coefficients and radii of gyration obtained as a function of ionic strength,
      persistence lengths (total, electrostatic, and intrinsic) were calculated from
      the Benoit-Doty relationship.

PMID- 17206796
TI  - Formation of polysaccharide gel layers in the presence of Ca2+ and K+ ions:
      measurements and mechanisms.
AB  - Understanding the adsorption properties of polysaccharides in terms of substrate
      affinity, kinetics, and layer structure is of paramount importance in numerous
      industrial and natural systems. The structural growth of the layers of two model
      polysaccharides--sodium alginate and polygalacturonic acid (PGA)--was
      characterized by quartz crystal microbalance with dissipation and atomic force
      microscopy. Monitoring the variations in frequency and dissipation energy
      provides insights into both the average adsorbed mass and the viscoelastic
      properties of the adsorbed layer of polyelectrolytes along with the associated
      ions and water molecules. Both polysaccharides had similar adsorption patterns
      with increasing ionic strengths and showed significant complexation of calcium
      ions. In the presence of calcium, the alginate gel layer exhibited significant
      swelling with an increasing concentration of monovalent salt that the PGA gel
      layer did not manifest. Basing our discussion on the "egg-box model", we
      interpreted these different swelling behaviors as resulting from differences in
      the complexation modes of the two polysaccharides. The dimerization of the
      polymers by cross-linking and the weaker dimer-dimer associations play major
      roles in the sensitivity of the polysaccharide gel matrix to high salt
      concentration environments.

PMID- 17206797
TI  - Development of biocompatible interpenetrating polymer networks containing a
      sulfobetaine-based polymer and a segmented polyurethane for protein resistance.
AB  - Interpenetrating polymer networks (IPNs) were prepared by the modification of a
      segmented polyurethane (SPU) with a cross-linked sulfobetaine methacrylate (SBMA)
      polymer. The IPN films that were prepared can effectively resist nonspecific
      protein adsorption when the distribution of SBMA units within the SPU film is
      well controlled, and they retain high mechanical strengths inherent from the base
      SPU films. Furthermore, the zwitterionic and biomimetic nature of sulfobetaine
      and the ease of SBMA preparation make SBMA-based materials very attractive for a
      wide range of applications. It is challenging to control the diffusion of highly
      polar SBMA into the hydrophobic network of SPU. In this study, various parameters
      governing the formation of IPNs containing SBMA were studied. The chemical
      composition depth profile of the IPN films was determined by confocal Raman
      microscopy. The morphology and thickness of these IPN films were examined by
      atomic force microscopy and scanning electron microscopy. The amount of adsorbed
      proteins on the IPN films was determined by an enzyme-linked immunosorbent assay.
      Results show that the amount of adsorbed proteins on the IPN films depends on the
      incubation conditions, including solvent polarity, incubation time, SBMA monomer
      ratio, and incubation concentration. It appears that the IPN films prepared in a
      mixed solvent of higher polarity with long incubation time lead to very low
      protein adsorption. This study not only introduces a new IPN system containing
      SBMA, but also provides a fundamental understanding of various parameters
      governing the formation of IPNs.

PMID- 17206798
TI  - Transformation of amyloid-like fibers, formed from an elastin-based biopolymer,
      into a hydrogel: an X-ray photoelectron spectroscopy and atomic force microscopy
      study.
AB  - Previous studies have revealed the propensity of elastin-based biopolymers to
      form amyloid-like fibers when dissolved in water. These are of interest when
      considered as "ancestral units" of elastin in which they represent the simplest
      sequences in the hydrophobic regions of the general type XxxGlyGlyZzzGly (Xxx,
      Zzz = Val, Leu). We normally refer to these biopolymers based on elastin or
      related to elastin units as "elastin-like polypeptides". The requirement of water
      for the formation of amyloids seems quite interesting and deserves investigation,
      the water representing the natural transport medium in human cells. As a matter
      of fact, the "natural" supramolecular organization of elastin is in the form of
      beaded-string-like filaments and not in the form of amyloids whose "in vivo"
      deposition is associated with some important human diseases. Our work is
      directed, therefore, to understanding the mechanism by which such hydrophobic
      sequences form amyloids and any conditions by which they might regress to a non
      amyloid filament. The elastin-like sequence here under investigation is the
      ValGlyGlyValGly pentapeptide that has been previously analyzed both in its
      monomer and polymer form. In particular, we have focused our investigation on the
      apparent stability of amyloids formed from poly(ValGlyGlyValGly), and we have
      observed these fibers evolving to a hydrogel after prolonged aging in water. We
      will show how atomic force microscopy can be combined with X-ray photoelectron
      spectroscopy to gain an insight into the spontaneous organization of an elastin
      like polypeptide driven by interfacial interactions. The results are discussed
      also in light of fractal-like assembly and their implications from a biomedical
      point of view.

PMID- 17206799
TI  - Multifunctional polyelectrolyte multilayer films: combining mechanical
      resistance, biodegradability, and bioactivity.
AB  - Cross-linked polyelectrolyte multilayer films (CL PEM) have an increased rigidity
      and are mechanically more resistant than native (e.g., uncrosslinked) films.
      However, they are still biodegradable, which make them interesting candidates for
      biomedical applications. In this study, CL PEM films have been explored for their
      multifunctional properties as (i) mechanically resistant, (ii) biodegradable, and
      (iii) bioactive films. Toward this end, we investigated drug loading into CL
      chitosan/hyaluronan (CHI/HA) and poly(L-lysine)/hyaluronan (PLL/HA) films by
      simple diffusion of the drugs. Sodium diclofenac and paclitaxel were chosen as
      model drugs and were successfully loaded into the films. The effect of varying
      the number of layers in the (CHI/HA) films as well as the cross-linker
      concentration on diclofenac loading were studied. Diclofenac was released from
      the film in about 10 h. Paclitaxel was also found to diffuse within CL films. Its
      activity was maintained after loading in the CL films, and cellular viability
      could be reduced by about 55% over 3 days. Such a simple approach may be applied
      to other types of cross-linked films and to other drugs. These results prove that
      it is possible to design multifunctional multilayer films that combine mechanical
      resistance, biodegradability, and bioactivity properties into a single PEM
      architecture.

PMID- 17206800
TI  - Preparation and characterization of nanoparticles shelled with chitosan for oral
      insulin delivery.
AB  - Nanoparticles (NPs) composed of chitosan (CS) and poly(gamma-glutamic acid)
      (gamma-PGA) were prepared by a simple ionic-gelation method for oral insulin
      delivery. Fourier transform infrared (FT-IR) spectra indicated that CS and gamma
      PGA were ionized at pH 2.5-6.6, while X-ray diffractograms demonstrated that the
      crystal structure of CS was disrupted after it was combined with gamma-PGA. The
      diameters of the prepared NPs were in the range of 110-150 nm with a negative or
      positive surface charge, depending on the relative concentrations of CS to gamma
      PGA used. The NPs with a positive surface charge (or shelled with CS) could
      transiently open the tight junctions between Caco-2 cells and thus increased the
      paracellular permeability. After loading of insulin, the NPs remained spherical
      and the insulin release profiles were significantly affected by their stability
      in distinct pH environments. The in vivo results clearly indicated that the
      insulin-loaded NPs could effectively reduce the blood glucose level in a diabetic
      rat model.

PMID- 17206801
TI  - Organocatalytic ring opening polymerization of trimethylene carbonate.
AB  - A variety of organocatalysts has been surveyed in the ring opening polymerization
      of trimethylene carbonate. Excellent control was found for several of these
      catalysts yielding well-defined polycarbonates with molecular weights up to
      50,000 g mol(-1), polydispersities below 1.08, and high end-group fidelity. Melt
      or bulk polymerization was accomplished without loss of control of molecular
      weight or polydispersity, and random ester-carbonate bulk polymerizations were
      also demonstrated. Furthermore, by combining disparate polymerization techniques
      using bifunctional initiators, the mild polymerization conditions allow for the
      preparation of new block copolymers. Hydrogen-bond activation of monomer and
      initiator/propagating species is proposed as the underlying mechanism, which can
      be tuned to mitigate adverse side reactions.

PMID- 17206802
TI  - Micropatterned thin film honeycomb materials from regiospecifically modified
      cellulose.
AB  - Thin film honeycomb materials were prepared from regioselectively modified
      celluloses. The method uses water condensation at the surface of a cellulosic
      solution as an ordered template to form honeycomb structures. Pore size and
      distribution is controlled by several factors, one of which is the hydrophilicity
      of the cellulosic used. The amphiphilic nature of the celluloses was modified
      with varying lengths of ethylene glycol side chains using 2,6-thexyldimethylsilyl
      cellulose. It was found that the side chains do affect the honeycomb formation,
      with longer ethylene glycol chains leading to increased pore uniformity but
      having little influence on the pore size.

PMID- 17206803
TI  - Terminal electron acceptors influence the quantity and chemical composition of
      capsular exopolymers produced by anaerobically growing Shewanella spp.
AB  - Bacterial exopolymers perform various roles, including acting as a carbon sink, a
      protective layer against desiccation or antimicrobial agents, or a structural
      matrix in biofilms. Despite such varied roles, little is known about the
      heterogeneity of bacterial exopolymer production under varying growth conditions.
      Here we describe experiments designed to characterize the quantity and quality of
      exopolymers produced by two commonly studied members of the widely distributed
      genus Shewanella. Electrokinetic, spectroscopic, and electron microscopic
      techniques were employed to demonstrate that cell surfaces of Shewanella
      oneidensis MR-1 (electrophoretic softness, lambda(-1), range from 0.4 to 2.6 nm)
      are associated with less extracellular polymeric material than surfaces of
      Shewanella putrefaciens 200R (lambda(-1) range from 1.6 to 3.0 nm). Both species
      exhibit similar responses to changes in electron acceptor with nitrate- and
      fumarate-grown cells producing relatively little exopolymer compared to
      trimethylamine N-oxide (TMAO)-grown cells. In S. oneidensis, the increase in
      exopolymers has no apparent effect upon cell-surface fixed charge density (-7.7
      to -8.7 mM), but for S. putrefaciens a significant drop in fixed charge density
      is observed between fumarate/nitrate-grown cells (-43 mM) and TMAO-grown cells (
      20.8 mM). For both species, exopolymers produced during growth on TMAO have
      significant amide functionality, increasing from approximately 20-25% of C
      containing moieties in nitrate-grown cells to over 30% for TMAO-grown cells
      (determined from X-ray photoelectron spectroscopy). The increased exopolymer
      layer associated with TMAO-grown cells appears as a continuous, convoluted layer
      covering the entire cell surface when viewed by low-temperature, high-resolution
      scanning electron microscopy. Such significant changes in cell-surface
      architecture, dependent upon the electron acceptor used for growth, are likely to
      influence a variety of cell interactions, including aggregation and attachment to
      surfaces, and the binding of aqueous metal species.

PMID- 17206804
TI  - Some observations on the structure and function of the spinning apparatus in the
      silkworm Bombyx mori.
AB  - Silkworm silk has outstanding mechanical properties despite being spun at room
      temperature and from aqueous solution. Although it has been proposed that fiber
      formation is mainly induced by shearing and extensional flow in the spinneret,
      the detailed structure and function of the spinning apparatus of Bombyx mori
      silkworms are still not fully elucidated. In this paper we describe three aspects
      of the functional microanatomy of the spinning apparatus: changes in the diameter
      of the silk gland duct with distance along the duct, how the birefringence of the
      fibroin changes as it flows down the duct, and the detailed three-dimensional
      structure of the silk press and related structures. The existence of a double
      escaped nematic liquid crystal texture in the fibroin in a region of the duct is
      described. After this region the birefringence suddenly disappeared until the
      start of an internal draw down taper which commenced just before the silk press.
      In the internal draw down taper the birefringence increased dramatically to an
      asymptotic value as a thread was drawn from the fibroin gel. The structure of the
      silk press suggests that it acts as a restriction die whose diameter can be
      regulated.

PMID- 17206805
TI  - Controlled amine functionalization on conducting polypyrrole nanotubes as
      effective transducers for volatile acetic acid.
AB  - Pristine (carboxylated) and aminated polypyrrole nanotubes were successfully
      fabricated using vapor deposition polymerization with a template. In particular,
      aminated polypyrrole nanotubes were readily synthesized by modifying the nanotube
      surface with open polyamine chains. Pristine and aminated polymer nanotubes were
      used as the transducer to acetic acid vapor. Amino-functionalized nanotubes
      revealed more enhanced sensitivity than the pristine carboxylated nanotubes with
      the increasing number of amine spacers due to the increased polymer/analyte
      partition coefficient and mass uptake of the analyte. Moreover, polyamine
      functionalized nanotubes presented a reversible and reproducible response to
      acetic acid up to 40% sensitivity. The aminated polypyrrole nanotubes
      demonstrated the potential capability to be excellent transducers for volatile
      fatty acids in disposable sensors.

PMID- 17206806
TI  - Chitinase-catalyzed synthesis of an alternatingly N-sulfonated chitin derivative.
AB  - An alternatingly N-sulfonated chitin derivative (2) was synthesized via ring
      opening polyaddition of an N-sulfonated chitobiose oxazoline derivative (1)
      catalyzed by chitinases from Bacillus sp. and Serratia marcescens. The
      polymerization proceeded homogeneously, providing 2 as a water-soluble
      polysaccharide in good yields with total control of regioselectivity and
      stereochemistry. M(n) of 2 reached 1900 and 4180 by use of chitinases from
      Bacillus sp. and Serratia marcescens, which correspond to 8-10 (n = 4-5) and 18
      20 (n = 9-10) saccharide units, respectively. These results indicate that M(n) of
      2 is controllable by selecting chitinases from different origins. It is
      considered that the C-2 position of the nonreducing unit in the oxazoline-type
      monomer is not deeply involved in the catalysis of chitinase.

PMID- 17206807
TI  - A new degradable hydroxamate linkage for pH-controlled drug delivery.
AB  - A new drug delivery system based on a hydrodegradable hydroxamate linkage was
      evaluated. The carrier support system was poly(N-hydroxyacrylamide), which was
      synthesized via free radical polymerization of acryloyl chloride in 1,4-dioxane,
      initiated with 2,2'-azobisisobutyronitrile. The poly(acryloyl chloride) was
      modified in two steps. First, N-hydroxysuccinimide was added to give the imide
      ester of poly(acryloyl). In the second step, the imide ester of poly(acryloyl)
      was reacted with either hydroxylamine or N-methylhydroxylamine to give the
      corresponding hydroxamic acid. The hydroxamide functionality was then used to
      link the model drug ketoprofen. All products and intermediates were characterized
      by elemental analysis and FTIR and 1H NMR spectra. In vitro drug release was
      performed under specific conditions to elucidate the influence of the pH, polymer
      microstructure, and temperature on the hydrolysis rate of the amido-ester bond
      that linked the drug to the macromolecule. The drug release rate from N
      methylhydroxamic acid polymers was faster than from hydroxamic acid polymers. All
      polymers showed higher rates of drug release at higher pH values (9.0 > 7.4 >
      2.0) and at higher temperatures (37 degrees C > 20 degrees C).

PMID- 17206808
TI  - Hydrotropic polymeric micelles for enhanced paclitaxel solubility: in vitro and
      in vivo characterization.
AB  - The purpose of this investigation was to characterize the in vitro stability and
      in vivo disposition of paclitaxel in rats after solubilization of paclitaxel into
      hydrotropic polymeric micelles. The amphiphilic block copolymers consisted of a
      micellar shell-forming poly(ethylene glycol) (PEG) block and a core-forming
      poly(2-(4-vinylbenzyloxy)-N,N-diethylnicotinamide) (P(VBODENA)) block. N,N
      Diethylnicotinamide (DENA) in the micellar inner core resulted in effective
      paclitaxel solubilization and stabilization. Solubilization of paclitaxel using
      polymeric micelles of poly(ethylene glycol)-b-P(D,L-lactide) (PEG-b-PLA) served
      as a control for the stability study. Up to 37.4 wt % paclitaxel could be loaded
      in PEG-b-P(VBODENA) micelles, whereas the maximum loading amount for PEG-b-PLA
      micelles was 27.6 wt %. Thermal analysis showed that paclitaxel in the polymeric
      micelles existed in the molecularly dispersed amorphous state even at loadings
      over 30 wt %. Paclitaxel-loaded hydrotropic polymeric micelles retained their
      stability in water for weeks, whereas paclitaxel-loaded PEG-b-PLA micelles
      precipitated in a few days. Hydrotropic polymer micelles were more effective than
      PEG-PLA micelle formulations in inhibiting the proliferation of human cancer
      cells. Paclitaxel in hydrotropic polymer micelles was administered orally (3.8
      mg/kg), intravenously (2.5 mg/kg), or via the portal vein (2.5 mg/kg) to rats.
      The oral bioavailability was 12.4% of the intravenous administration. Our data
      suggest that polymeric micelles with a hydrotropic structure are superior as a
      carrier of paclitaxel due to a high solubilizing capacity combined with long-term
      stability, which has not been accomplished by other existing polymeric micelle
      systems.

PMID- 17206809
TI  - Michael-type addition reactions for the in situ formation of poly(vinyl alcohol)
      based hydrogels.
AB  - Michael-type addition reactions offer the possibility to obtain in situ formation
      of polymeric hydrogels in the absence of a radical mechanism for the networking
      process. We explored such a synthetic route for obtaining a poly(vinyl alcohol)
      (PVA)-based hydrogel as a potential biomaterial for applications in vitro-retinal
      replacement surgery. The presence of radicals in the reaction medium can
      represent a risk for in situ surgical treatment. To circumvent this problem we
      have applied nucleophilic addition to ad hoc modified PVA macromers. The gel
      formation has been studied with respect to the timing required in this surgery
      and in terms of the structural characteristics of the obtained network.

PMID- 17206810
TI  - Size control of silica nanoparticles and their surface treatment for fabrication
      of dental nanocomposites.
AB  - Nearly monodispersed silica nanoparticles having a controlled size from 5 to 450
      nm were synthesized via a sol-gel process, and then the optimum conditions for
      the surface treatment of the synthesized silica nanoparticles with a silane
      coupling agent (i.e., 3-methacryloxypropyltrimethoxysilane (gamma-MPS)) were
      explored to produce dental composites exhibiting enhanced adhesion and dispersion
      of silica nanoparticles in the resin matrix. The particle size was increased by
      increasing amounts of the catalyst (NH4OH) and silica precursor
      (tetraethylorthosilicate, TEOS) and by decreasing the amount of water in the
      reaction mixtures regardless of solvents used for the synthesis. The particle
      size prepared by using ethanol as a solvent was significantly larger than that
      prepared by using methanol as a solvent when the composition of the reaction
      mixture was fixed. The nanosized particles in the 5-25 nm range were aggregated.
      The amount of grafted gamma-MPS on the surface of the synthesized silica
      nanoparticles was dependent on the composition of the reaction mixture when an
      excess amount of gamma-MPS was used. When surface treatment was performed at
      optimum conditions found here, the amount of the grafted gamma-MPS per unit
      surface area of the silica nanoparticles was nearly the same regardless of the
      particle size. Dispersion of the silica particles in the resin matrix and
      interfacial adhesion between silica particles and resin matrix were enhanced when
      surface treated silica nanoparticles were used for preparing dental
      nanocomposites.

PMID- 17206811
TI  - Assessment of in vitro binding of isolated pectic domains to cellulose by
      adsorption isotherms, electron microscopy, and X-ray diffraction methods.
AB  - Isolated pectic domains representative of the pectic backbone and the neutral
      sugar side chains were tested for their ability to interact with cellulose in
      comparison to the well-known binding of xyloglucan. Pectic side chains displayed
      a significant in vitro binding capacity to cellulose, whereas pectic backbone
      domains exhibited only slight adsorption to cellulose microfibrils. To support
      the binding results, electron microscopy and X-ray diffraction were applied.
      Celluloses from bacteria and sugar beet cell walls were used as substrates for
      the precipitation of isolated pectic domains or xyloglucan by acetone vapor
      diffusion. Pectic side chains grew attached to the cellulose surfaces, whereas
      pectic backbone domains were observed separately from cellulose microfibrils.
      Xyloglucan seeded with cellulose provoked a decrease of microfibrils
      entanglement, but no clear cross-links between neighboring microfibrils were
      observed. These results led to the elucidation of the pectic domains responsible
      for binding with cellulose microfibrils.

PMID- 17206812
TI  - From oligomers to molecular giants of soybean oil in supercritical carbon dioxide
      medium: 1. Preparation of polymers with lower molecular weight from soybean oil.
AB  - Polymers with a low molecular weight derived from soybean oil have been prepared
      in a supercritical carbon dioxide medium by cationic polymerization. Boron
      trifluoride diethyl etherate was used as an initiator. Influences of
      polymerization temperature, amount of initiator, and carbon dioxide pressure on
      the molecular weight were investigated. It is shown that the higher
      polymerization temperature favors polymers with relatively higher molecular
      weights. Larger amounts of initiator also provide polymers with higher molecular
      weights. Higher pressure favors polymers with relatively higher molecular
      weights. The applications of these soy-based materials will be in the lubrication
      and hydraulic fluid areas.

PMID- 17206813
TI  - Blends of reverse enteric polymer with Enteric and pH-independent polymers:
      mechanistic investigations for tailoring drug release.
AB  - Blends of conventional reverse enteric polymer with enteric polymers result in
      insoluble polyelectrolyte complexes and hence cannot be used in film coatings. We
      report a new set of miscible blends of a new reverse enteric polymer (NREP)
      synthesized by us with enteric and pH-independent polymers. The nature of
      interactions between polymers in the blends has been established by analyzing
      Fourier transform infrared (FTIR) spectra. The extent of interaction has been
      investigated by thermal analysis and quantified in terms of parameters K1 and K2
      in the Schneider equation. Based on these values, the interactions between NREP
      and these polymers have been ranked in the order EC (ethylcellulose) < ES
      (Eudragit S) < HPMCP (hydroxypropyl methylcellulose phthalate). The
      quantification of interactions in blends helps explain the release pattern of
      cefuroxime axetil (CA) at gastric pH and tailor the release of other drugs
      according to their pharmacokinetic characteristics. The understanding also
      provides a more rational approach for selection of polymers and their content in
      the coating compositions, rather than an empirical approach.

PMID- 17206814
TI  - Alpha-chitin nanocrystals prepared from shrimp shells and their specific surface
      area measurement.
AB  - Alpha-chitin was isolated from shrimp shells. The chitin was subjected to
      extensive treatments of acid hydrolysis and mechanical disruption to yield
      nanocrystals. The goal of this article is to characterize alpha-chitin
      nanocrystals produced from shrimp shells in regard to crystallite properties and
      the specific surface area of the chitin nanoparticles. X-ray diffraction data
      indicate an increase in chitin crystallinity after hydrolysis, as less-ordered
      chitin domains are digested. Line broadening data were used to measure
      crystallite size and particle size in the hydrolyzed chitin nanocrystals. Dye
      adsorption with Congo red was used to measure the specific surface area of the
      particles, indicating values near 350 m2/g. This value was supported with
      calculations derived from X-ray crystallite size measurements. Particle surface
      area measurements were compared with similarly prepared cellulose nanocrystals.

PMID- 17206815
TI  - Effect of silk fibroin interpenetrating networks on swelling/deswelling kinetics
      and rheological properties of poly(N-isopropylacrylamide) hydrogels.
AB  - Novel protein/synthetic polymer hybrid interpenetrating polymer networks (IPNs)
      of poly(N-isopropylacrylamide) (PNIPAAm) with Bombyx mori silk fibroin (SF) have
      been prepared by using methanol to postinduce SF crystallization. Those IPNs
      having the beta sheet crystalline structure of SF show improved storage and loss
      moduli. The IPN hydrogels show the same volume phase transition temperature and
      NaCl concentration as pure PNIPAAm hydrogels. The PNIPAAm/SF IPNs keep the
      swelling kinetics of PNIPAAm, while showing increased deswelling kinetics. The
      IPNs with SF beta sheet structure should decrease the formation of the skin layer
      observed in conventional PNIPAAm hydrogels. Therefore, the proposed IPN hydrogels
      composed of protein/polymer provide fast deswelling rates as well as improved
      mechanical properties over pure PNIPAAm hydrogels. The effect of SF beta sheet
      networks on the IPNs copolymerized with acrylic acid (AAc) (P(NIPAAm-co-AAc)/SF
      IPNs) is compared with that on the PNIPAAm/SF IPNs, and the parameters
      controlling the deswelling kinetics of the IPNs are investigated. Three
      parameters, (1) the skin layer formation, (2) the restriction of SF beta sheet
      networks, and (3) the aggregation force of NIPAAm chains, are cooperatively
      involved in the deswelling process of IPN hydrogels according to the SF content
      and the presence of the AAc moiety.

PMID- 17206816
TI  - Development of improved nanoparticulate polyelectrolyte complex physicochemistry
      by nonstoichiometric mixing of polyions with similar molecular weights.
AB  - Water-based, biodegradable polyelectrolyte complex dispersions (PECs) prepared by
      mixing oppositely charged polyions are advantageous drug delivery systems due to
      constituent biocompatibility and nanoparticulate architectures. Reaction phase
      environmental parameters dictate PEC physicochemical properties, and
      specifically, complexation between polyelectrolytes having significantly
      different molecular weights leads to formation of water-insoluble aggregates.
      Starting with this fact, four-component similar and dissimilar molecular weight
      PEC chemistries were applied and compared with and without frequency-induced
      dispergation. The goal was to define nanoparticulate PEC systems with desirable
      characteristics for use in biological systems. Results show PEC formulations from
      precursors with similar low molecular weights yielded dispersions with suitable
      physicochemical characteristics, as verified by photon correlation spectroscopy
      and TEM, presumably due to efficient ion pairing. Similar low molecular weight
      PECs fabricated with dispergation exhibited pH-independent stability, as
      validated by charge and size measurements. These physicochemical advantages lead
      to an ideal delivery platform.

PMID- 17206817
TI  - Weak interaction induces an ON/OFF switch, whereas strong interaction causes
      gradual change: folding transition of a long duplex DNA chain by poly-L-lysine.
AB  - A large-scale conformational change in genomic DNA is an essential feature of
      gene activation in living cells. Considerable effort has been applied to explain
      the mechanism in terms of key-lock interaction between sequence-specific
      regulatory proteins and DNA, in addition to the modification of DNA and histones
      such as methylation and acetylation. However, it is still unclear whether these
      mechanisms can explain the ON/OFF switching of a large number of genes that
      accompanies differentiation, carcinogenesis, etc. In this study, using single
      molecule observation of DNA molecules by fluorescence microscopy with the
      addition of poly-L-lysine with different numbers of monomer units (n = 3, 5, 9,
      and 92), we found that an ON/OFF discrete transition in the higher-order
      structure of long duplex DNA is induced by short poly-L-lysine, whereas a
      continuous gradual change is induced by long poly-L-lysine. On the other hand,
      polycations with a lower positive charge have less potential to induce DNA
      compaction. Such a drastic difference in the conformational transition of a giant
      DNA between short and large oligomers is discussed in relation to the mechanisms
      of gene regulation in a living cell.

PMID- 17206818
TI  - Efficient production of (R)-3-hydroxycarboxylic acids by biotechnological
      conversion of polyhydroxyalkanoates and their purification.
AB  - An efficient method to prepare enantiomerically pure (R)-3-hydroxycarboxylic
      acids from bacterial polyhydroxyalkanoates (PHAs) accumulated by Pseudomonas
      putida GPo1 is reported in this study. (R)-3-Hydroxycarboxylic acids from whole
      cells were obtained when conditions were provided to promote in vivo
      depolymerization of intracellular PHA. The monomers were secreted into the
      extracellular environment. They were separated and purified by acidic
      precipitation, preparative reversed-phase column chromatography, and subsequent
      solvent extraction. Eight (R)-3-hydroxycarboxylic acids were isolated: (R)-3
      hydroxyoctanoic acid, (R)-3-hydroxyhexanoic acid, (R)-3-hydroxy-10-undecenoic
      acid, (R)-3-hydroxy-8-nonenoic acid, (R)-3-hydroxy-6-heptenoic acid, (R)-3
      hydroxyundecanoic acid, (R)-3-hydroxynonanoic acid, and (R)-3-hydroxyheptanoic
      acid. The overall yield based on released monomers was around 78 wt % for (R)-3
      hydroxyoctanoic acid. All obtained monomers had a purity of over 95 wt %. The
      physical properties of the purified monomers and their antimicrobial activities
      were also investigated.

PMID- 17206819
TI  - Photografted poly(ethylene glycol) matrix for affinity interaction studies.
AB  - A poly(ethylene glycol) (PEG)-based matrix for studies of affinity interactions
      is developed and demonstrated. The PEG matrix, less than 0.1 microm thick, is
      graft copolymerized onto a cycloolefin polymer from a mixture of PEG
      methacrylates using a free radical reaction initiated by UV light at 254 nm. The
      grafting process is monitored in real time, and characteristics such as
      thickness, homogeneity, relative composition, photostability, and performance in
      terms of protein resistance in complex biofluids and sensor qualities are
      investigated with null ellipsometry, infrared spectroscopy, and surface plasmon
      resonance. The matrix is subsequently modified to contain carboxyl groups,
      thereby making it possible to immobilize ligands in a controlled and functional
      manner. Human serum albumin and fibrinogen are immobilized and successfully
      detected by antibody recognition using surface plasmon resonance. The results are
      encouraging and suggest that the PEG matrix is suitable for biochip and biosensor
      applications in demanding biofluids.

PMID- 17206820
TI  - A study of water diffusion into a high-amylose starch blend: the effect of
      moisture content and temperature.
AB  - The effect of moisture content and temperature on water diffusion into a modified
      high amylose (< or = 90%) maize thermoplastic starch blend was investigated.
      Gravimetric and magnetic resonance imaging (MRI) studies were conducted to
      elucidate the diffusion mechanism and diffusion coefficients for this system. The
      diffusion coefficient data demonstrated that the rate of water diffusion into
      this blend was significantly dependent upon temperature and moisture content.
      Water diffusion was faster at higher temperatures and generally for samples
      stored at higher relative humidity environments. It was revealed from the
      gravimetric data that water diffusion into this starch blend was Fickian;
      however, further analysis of the MRI images found that the water diffusion
      mechanism was exponentially dependent on the concentration. This result was
      determined by comparing experimental water concentration profiles to a
      theoretical model calculated using the implicit Crank-Nicolson finite difference
      method.

PMID- 17206821
TI  - Association of star-shaped poly(D,L-lactide)s containing nucleobase multiple
      hydrogen bonding.
AB  - A new family of associating polymers based on four-arm, star-shaped poly(D,L
      lactide) (PDLLA) containing peripheral complementary hydrogen-bonding sites is
      described. Hydroxy-terminated, four-arm, star-shaped PDLLAs of controlled molar
      mass were functionalized with complementary DNA base pairs, adenine (A) and
      thymine (T), to obtain PDLLA-A and PDLLA-T, respectively. 1H NMR spectroscopy
      confirmed quantitative functionalization and the subsequent formation of PDLLA-A
      and PDLLA-T hydrogen-bonded complexes. Job's analysis revealed a 1:1 optimal
      stoichiometry for the hydrogen-bonded complexes, and the association constant
      (Ka) that was determined using the 1H NMR-based Benesi-Hildebrand treatment was
      84 M(-1) for the low molar mass complementary polymers. Furthermore, the PDLLA
      based hydrogen-bonded complexes exhibited higher solution viscosities compared to
      the corresponding non-hydrogen-bonded precursors, which further confirmed strong
      complementary multiple-hydrogen-bonding associations between the star-shaped
      polymers with terminal adenine and thymine groups. Moreover, variable-temperature
      1H NMR studies demonstrated the thermoreversibility of the hydrogen-bonded PDLLA
      based complexes in solution.

PMID- 17206822
TI  - Depolymerization and de-N-acetylation of chitin oligomers in hydrochloric acid.
AB  - The monosaccharide 2-amino-2-deoxy-D-glucose (glucosamine, GlcN) has recently
      drawn much attention in relation to its use to treat or prevent osteoarthritis in
      humans. Glucosamine is prepared from chitin, a process that is performed in
      concentrated acid, such as hydrochloric acid. This process involves two acid
      catalyzed processes, that is, the hydrolysis of the glycosidic linkages
      (depolymerization) and of the N-acetyl linkages (de-N-acetylation). The
      depolymerization reaction has previously been found to be much faster compared to
      the deacetylation, with the consequence that the chitin chain will first be
      hydrolyzed to the monomer 2-acetamido-2-deoxy-D-glucose (N-acetylglucosamine,
      GlcNAc) which is subsequently deacetylated. We have found that the chitin
      disaccharide GlcNAc(1-->4)GlcNAc could be completely hydrolyzed to the
      monosaccharide GlcNAc with negligible concomitant de-N-acetylation, and the
      chitin disaccharide and monosaccharide were further used to study the
      depolymerization reaction and the de-N-acetylation reaction, respectively. The
      reactions were performed in hydrochloric acid as a function of acid concentration
      (3-12 M) and temperature (20-35 degrees C), and 1H-NMR spectroscopy was used to
      monitor the reaction rates. The 1H NMR spectrum of GlcNAc in concentrated (12 M)
      and deuterated hydrochloric acid at 25 degrees C was assigned. The glucofuranosyl
      oxazolinium (3) ion was found to exist in equilibrium with the alpha- and beta
      anomers of the pyranose form of GlcNAc, where 3 was present in half the total
      molar concentrations of the two anomeric forms of GlcNAc. At lower acid
      concentration (3-6 M), only trace concentrations of 3 could be detected. The rate
      of de-N-acetylation of GlcNAc was determined as a function of hydrochloric acid
      concentration, showing a maximum at 6 M and decreasing by a factor of 2 upon
      decreasing or increasing the acid concentration to 3 or 12 M. The activation
      energy for hydrolysis of the N-acetyl linkage of GlcNAc was determined to be 102
      +/- 7, 116 +/- 8, and 110 +/- 8 kJ mol(-1) at 3, 6, and 12 M hydrochloric acid
      concentration, respectively. The results are in accordance with the proposed SN2
      reaction mechanism of the acid-catalyzed hydrolysis of the N-acetyl linkage where
      the rate-limiting step is the addition of water to the carbonium ion. The 1H NMR
      spectrum of the dimer GlcNAc-GlcNAc in concentrated (12 M) and deuterated
      hydrochloric acid at 25 degrees C was assigned. The rate of the acid-catalyzed
      cleavage of the glycosidic linkage of the dimer was determined as a function of
      hydrochloric acid concentration, showing a 6-fold increase from 3 to 6 M HCl
      concentration and a further 6-fold increase from 6 to 12 M HCl concentration, in
      contrast to the much smaller effect of acid concentration on the deacetylation
      reaction. Activation energy for hydrolysis of the glycosidic linkage of GlcNAc
      GlcNAc was determined to be 110 +/- 6, 111 +/- 6, and 112 +/- 4 kJ mol(-1) at 3,
      6 and 12 M hydrochloric acid concentration, respectively, that is, very similar
      to the activation energies determined for the deacetylation reaction. The results
      are in accordance with the proposed SN1 reaction mechanism of the acid-catalyzed
      hydrolysis of the glycosidic linkage, where the rate-limiting step is the
      formation of the carbonium ion.

PMID- 17206823
TI  - Two galactosyltransferases' selection of different binders from the same uridine
      based dynamic combinatorial library.

PMID- 17206824
TI  - Parallel liquid-phase synthesis of benzopyrano[2,3-d]pyrimidine libraries.

PMID- 17206825
TI  - Scaffold approach for solid-phase synthesis of 2,3-disubstituted 8-arylamino-3H
      imidazo[4,5-g]quinazolines.

PMID- 17206826
TI  - Three-component, one-pot synthesis of 2,4,5-substituted pyrimidines library for
      screening against human hepatocellular carcinoma BEL-7402 cells.

PMID- 17206827
TI  - Multicomponent reactions to form heterocycles by microwave-assisted continuous
      flow organic synthesis.

PMID- 17206828
TI  - Sonication-assisted library synthesis of oxazolidinone-carbohydrate conjugates.

PMID- 17206829
TI  - Solution-phase parallel synthesis of a library of delta(2)-pyrazolines.
AB  - A parallel synthesis of a library (80 members) of 2-pyrazolines in solution phase
      is described. The 2-pyrazoline core was accessed through the [3 + 2]
      cycloaddition of nitrilimines with enoyl oxazolidinones. The cycloaddition
      provided two regioisomers, the major product being the C regioisomer. The
      oxazolidinone moiety was further reduced to the primary alcohol, producing
      another library of 5-hydroxymethyl-2-pyrazolines. The Lipinski profiles and
      calculated ADME properties of the compounds are also reported.

PMID- 17206830
TI  - Solid-phase synthesis of a library of pyrrolo[2,1-c][1,4]benzodiazepine-5,11
      diones with potential antitubercular activity.
AB  - A versatile combinatorial approach was developed and utilized for the rapid
      synthesis of pyrrolo[2,1-c]-[1,4]benzodiazepine-5,11-dione (PBD-5,11-dione)
      libraries 10, 15, and 19 containing 210 compounds with varied substitutions in A,
      B, and C rings. The key aspect of the synthetic strategy includes Staudinger,
      intermolecular aza-Wittig reaction followed by imine reduction and base-mediated
      cyclative cleavage results in the formation of final resin-free compounds. This
      strategy provides a highly efficient and practical protocol for the parallel
      synthesis of PBD-5,11-diones on solid support. The modifications in the C-ring of
      the PBD scaffold produced three types of sublibraries. Reactions were monitored
      by FT-IR spectroscopy on the resin beads. Further, from a generated library of
      210 compounds, 142 compounds have been selected and evaluated for in vitro
      activity against Mycobacterium tuberculosis, and some of these compounds have
      exhibited promising activity.

PMID- 17206831
TI  - Combinatorial approach to N-substituted aminocyclitol libraries by solution-phase
      parallel synthesis and preliminary evaluation as glucocerebrosidase inhibitors.
AB  - Libraries of N-substituted aminocyclitol derivatives of the scyllo and racemic
      chiro series by means of parallel solution-phase methodology with the help of
      robotic technology are described. Chemical diversity has been introduced by
      reaction of selected scaffolds with a set of aldehydes, acyl chlorides, sulfonyl
      chlorides, chloroformates, and amines to afford the corresponding amines, amides,
      sulfonamides, carbamates and ureas, respectively. The optimized methodology has
      proven excellent, in terms of overall purities of the resulting libraries, for
      the production of amides. Sulfonamides and carbamates have been obtained in
      slightly lower purities, while amines afforded modest results. Selected library
      members have been evaluated as inhibitors of recombinant glucocerebrosidase with
      K(i) values ranging in the low micromolar scale for the most active members.

PMID- 17206832
TI  - High-throughput gas sensing screening of surface-doped In(2)O(3).
AB  - The effect of various surface doping elements on the electrical and gas sensing
      properties of indium(III) oxide thick films sensors was investigated by means of
      high-throughput impedance spectroscopy (HTIS). Some doping elements lead to
      changes in both the conductivity in air as well as in the gas sensing properties
      towards oxidizing (NO(2), NO) and reducing (H(2), CO, propene) gases.
      Correlations between the sensing and the electrical properties in reference
      atmosphere indicate that the effect of the doping elements can be ascribed to an
      influence on the oxidation state of the metal oxide surface rather that to an
      interaction with the respective testing gases. An equation for the description of
      the temperature-dependent conductivity in air and nitrogen is proposed to
      describe the oxidation state of the metal oxide surface taking into account
      sorption of oxygen. Furthermore, a model associating the sensing properties and
      the oxidation state of the surface layer of the metal oxide based on oxygen
      spillover from doping element particles to the metal oxide surface is introduced.

PMID- 17206833
TI  - Diversely substituted sugar-linked alpha,beta-unsaturated gamma-lactones from
      sugar-derived Baylis-Hillman adducts via a RCM.
AB  - A versatile protocol for the production of sugar-linked alpha,beta-unsaturated
      gamma-lactones with stereochemical and functional group diversity is described
      starting from sugar-derived Baylis-Hillman adducts via ring-closing metathesis.

PMID- 17206834
TI  - Benzofused tricycles based on 2-quinoxalinol.
AB  - This paper describes our recent efforts to synthesize novel compound scaffolds
      integrating 2-quinoxalinol with privileged structures of 1,3-dihydro
      benzoimidazol-2-one, 1,3-dihydro-benzoimidazole-2-thione, 3-hydroxy-1H-quinoxalin
      2-one, 2H-benzo[1,4]oxazin-3-ol, 2H-benzo[1,4]thiazin-3-ol, and 1,3,4,5
      tetrahydro-benzo[1,4]diazepin-2-one, respectively. Eight novel benzofused
      tricycles and their substituent diversity points were developed. These include
      pyrazino[2,3-g]quinoxaline-2,8-diol (I), 3-hydroxy-6,8,9,10-tetrahydro-1,4,6,10
      tetraaza-cyclohepta[b]naphthalen-7-one (II), 6-hydroxy-4H-1-oxa-4,5,8-triaza
      anthracen-3-one (III), 6-hydroxy-4H-1-thia-4,5,8-triaza-anthracen-3-one (IV), 6
      hydroxy-1,1-dioxo-1,4-dihydro-2H-1lambda(6)-thia-4,5,8-triaza-anthracen-3-one
      (V), 6-hydroxy-1,3-dihydro-imidazo[4,5-g]quinoxalin-2-one (VI), 6-hydroxy-1,3
      dihydro-imidazo[4,5-g]quinoxaline-2-thione (VII), and 7-hydroxy-1,4-dihydro
      pyrazino[2,3-g]quinoxaline-2,3-dione (VIII). This strategy of integrating two
      benzofused privileged structures into one molecule may provide a greater chance
      for the discovery of novel lead compounds.

PMID- 17206835
TI  - Solid-phase synthesis of a peptide-based P,S-ligand system designed for
      generation of combinatorial catalyst libraries.
AB  - An efficient methodology for the solid-phase synthesis of diverse combinatorial
      peptide-based P,S-ligand libraries based on a modular approach was developed.
      Chiral thioethers were introduced into a series of peptide scaffolds using
      commercially available Fmoc-protected cysteine derivatives, and secondary amines
      were incorporated into the peptide backbones by reductive alkylation using
      readily available Fmoc-protected amino aldehydes. Phosphinylation of the
      secondary amines of the scaffolds, applying two different reagents, yielded two
      different types of ligands. Subsequent complexation with palladium afforded six-
      or seven-membered chelates, respectively. The selectivity, in an asymmetric
      allylic substitution reaction, of the two different types of chelates, derived
      from the same peptide scaffold, was complementary in all cases studied, affording
      the product as opposite stereoisomers with up to 60% ee. These results hold great
      promise for the identification of highly selective catalysts upon screening of
      larger P,S-based catalyst libraries.

PMID- 17206836
TI  - Solution-phase parallel synthesis of 3,5,6-substituted indolin-2-ones.
AB  - A practical and efficient new parallel method has been developed for the
      synthesis of 3-substituted indolin-2-ones with a large variety of substituents at
      the 5- and 6-positions using 1,5-difluoro-2,4-dinitrobenzene. This 3,5,6
      substituted indolin-2-one skeleton possesses three points of diversification and,
      thus, affords new opportunities for identification and optimization of leads in
      drug discovery.

PMID- 17206837
TI  - Synthesis of heterocyclic compounds possessing the 4H-thieno[3,2-b]pyrrole
      moiety.
AB  - A series of novel heterocyclic combinatorial libraries containing 4H-thieno[3,2
      b]pyrrole, thieno[2',3':4,5]-pyrrol[1,2-d][1,2,4]triazine and
      thieno[2',3':4,5]pyrrolo[1,2-a]pyrazine heterocyclic moieties were obtained by
      parallel solution-phase synthesis. Key steps include different reactions of
      initial alkyl 4H-thieno[3,2-b]-pyrrole-5-carboxylates, such as alkylation with
      alkylating agents; transformation of the carboxylate group into different
      reactive functionalities, followed by reactions with electrophilic species;
      intramolecular cyclizations; and amide bond formation. Simple manual techniques
      for parallel reactions were coupled with easy purification procedures to give
      high-purity final products.

PMID- 17206838
TI  - Design and synthesis of an array of selective androgen receptor modulators.
AB  - We describe the design, using shape comparison and fast docking computer
      algorithms, and rapid parallel synthesis of a 1300 member array based on GSK7721,
      a 4-aminobenzonitrile androgen receptor (AR) antagonist identified by focused
      screening of the GSK compound collection. The array yielded 352 submicromolar and
      17 subnanomolar AR agonists as measured by a cell-based reporter gene functional
      assay. The rapid synthesis of a large number of active compounds provided
      valuable information in the optimization of AR modulators, which may be useful in
      treating androgen deficiency in aging males.

PMID- 17206839
TI  - Multipolymer reaction system for selective aerobic alcohol oxidation:
      simultaneous use of multiple different polymer-supported ligands.
AB  - A multipolymer reaction system has been developed in which a water-soluble
      polymer-supported 2,2'-bipyridine group and a similarly immobilized TEMPO
      derivative are used as ligands for copper to effect the mild and selective
      aerobic oxidation of primary alcohols in acetonitrile-water solvent. In this
      reaction system, poly(ethylene glycol) monomethyl ether (molecular weight = 5000
      Da) was used as the support for both the 2,2'-bipyridine and TEMPO moieties
      because of its solubility properties. The use of these functionalized polymers
      simultaneously in catalytic quantities allows for primary alcohols to be oxidized
      selectively to the corresponding aldehydes in an environmentally friendly manner.
      This is the first reported example of using two different polymer-supported
      ligands together to form an organometallic species capable of catalyzing an
      organic reaction.

PMID- 17206840
TI  - Solid-phase synthesis of linked heterocycles from a selenopolystyrene resin.
AB  - A linked heterocycle library of isoxazoles, 1,2,3-triazoles, bicyclo[2.2.1]hepta
      2,5-diene or 4-methylcyclohexa-1,3-diene and 1,2,4-oxadiazoles was prepared by
      solid-phase organic synthesis. Key steps on resin-bound selenium were
      electrophilic additions; 1,3-dipolar cycloaddition; Porco's two-step, one-pot
      condensation of amidoxime and carboxylate; and Diels-Alder reaction.

PMID- 17206841
TI  - Structure-based rational quest for potential novel inhibitors of human HMG-CoA
      reductase by combining CoMFA 3D QSAR modeling and virtual screening.
AB  - 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) catalyzes the formation of
      mevalonate. In many classes of organisms, this is the committed step leading to
      the synthesis of essential compounds, such as cholesterol. However, a high level
      of cholesterol is an important risk factor for coronary heart disease, for which
      an effective clinical treatment is to block HMGR using inhibitors like statins.
      Recently the structures of catalytic portion of human HMGR complexed with six
      different statins have been determined by a delicate crystallography study
      (Istvan and Deisenhofer Science 2001, 292, 1160-1164), which established a solid
      basis of structure and mechanism for the rational design, optimization, and
      development of even better HMGR inhibitors. In this study, three-dimensional
      quantitative structure-activity relationship (3D QSAR) with comparative molecular
      field analysis (CoMFA) was performed on a training set of up to 35 statins and
      statin-like compounds. Predictive models were established by using two different
      ways: (1) Models-fit, obtained by SYBYL conventional fit-atom molecular alignment
      rule, has cross-validated coefficients (q2) up to 0.652 and regression
      coefficients (r2) up to 0.977. (2) Models-dock, obtained by FlexE by docking
      compounds into the HMGR active site, has cross-validated coefficients (q2) up to
      0.731 and regression coefficients (r2) up to 0.947. These models were further
      validated by an external testing set of 12 statins and statin-like compounds.
      Integrated with CoMFA 3D QSAR predictive models, molecular surface property
      (electrostatic and steric) mapping and structure-based (both ligand and receptor)
      virtual screening have been employed to explore potential novel hits for the HMGR
      inhibitors. A representative set of eight new compounds of non-statin-like
      structures but with high pIC(50) values were sorted out in the present study.

PMID- 17206842
TI  - Selective nucleophilic chemistry in the synthesis of 5-carbamoyl-3
      sulfanylmethylisoxazole-4-carboxylic acids.
AB  - The solution-phase syntheses of 5-carbamoyl-3-sulfanylmethylisoxazole-4
      carboxylic acids were accomplished from dimethyl 3-chloromethylisoxazole-4,5
      dicarboxylate by selective nucleophilic chemistry. For example, treatment of this
      trifunctionalized core with 3-bromobenzylamine and subsequent X-ray analysis
      identified the sole product as methyl 5-(3-bromobenzylcarbamoyl)-3
      chloromethylisoxazole-4-carboxylate. Subjecting this amide/ester to thiophenol in
      the presence of 1 N NaOH completed the two-step transformation of this versatile
      starting material to the targeted 5-carbamoyl-3-sulfanylmethylisoxazole-4
      carboxylic acid. Employing various amines and thiophenols, this chemistry was
      applied in the generation of a 90-compound library of druglike isoxazoles.

PMID- 17206843
TI  - A spiroisoxazolinoproline-based amino acid scaffold for solid phase and one-bead
      one-compound library synthesis.
AB  - An efficient, multigram synthesis of a spiroisoxazolinoproline-based amino acid,
      7, requiring minimal purification, delivering good cis:trans diastereoselectivity
      (approximately 1:4), and providing good yields is reported. Surface-bound studies
      of the reduction of an arylnitro group in the presence of an isoxazoline ring
      with tin(II) dichloride dihydrate were undertaken to confirm the stability of the
      isoxazoline ring. Full derivitization of this spiroisoxazolinoproline-based amino
      acid scaffold was performed during the synthesis of a sample library with high
      yields and high purity that validated the efficiency of the chemistry that was
      employed in resin-bound library synthesis. A 129,600 member one-bead-one-compound
      (OBOC) library based on the scaffold 7 was synthesized utilizing a dual amino
      acid encoding method and bifunctionalization of TentaGel resin.

PMID- 17206844
TI  - Synthesis of diverse benzo[1,4]oxazin-3-one-based compounds using 1,5-difluoro
      2,4-dinitrobenzene.
AB  - This paper discusses the synthesis of benzo[1,4]oxazin-3-one-based compounds from
      1,5-difluoro-2,4-dinitrobenzene (1), including benzo[1,4]oxazin-3-ones (5-11) and
      five novel benzo[1,4]oxazin-3-one-based tricycles: 6-hydroxy-4H-1-oxa-4,5,8
      triazaanthracen-3-one (14), 3,8-dihydro-5-oxa-1,3,8-triazacyclopenta-[b]
      naphthalene-7-one (15, 17, 21), 3,8-dihydro-5-oxa-1,2,3,8-tetraazacylopenta[b]
      naphthalene-7-one (16, 20), 3,8-dihydro-1H-5-oxa-1,3,8-triazacyclopenta[b]
      naphthalene-2,7-dione (18, 22), and 5,8-dihydro-4H-1-oxa-4,5,8-triazaanthracene
      3,6,7-trione (19). Finally, a chemical library based on 15 was synthesized in
      parallel solution-phase reactions.

PMID- 17206845
TI  - Synthesis of a library of 2-alkyl-3-alkyloxy-2H-indazole-6-carboxamides.
AB  - A library of 200 2-alkyl-3-alkyloxy-2H-indazole-6-carboxamides was synthesized
      using parallel solution-phase methods. The indazole cyclization reaction was
      optimized for library production with the best yields resulting from controlled
      alcohol/water solvent ratios. The key step, a heterocyclization reaction,
      proceeds by N,N-bond formation and delivers the 2H-indazole scaffold. Automated
      preparative HPLC was utilized to provide pure compounds on a 10+ mg scale.

PMID- 17206846
TI  - Combinatorial and high-throughput screening of the effect of siloxane composition
      on the surface properties of crosslinked siloxane-polyurethane coatings.
AB  - Libraries of siloxane-polyurethane coatings were designed, formulated, and
      screened using high-throughput experimentation. Four independent variables that
      were analyzed were the molecular weight of poly(dimethylsiloxane) (PDMS),
      presence or absence of poly(epsilon-caprolactone) (PCL) blocks attached to the
      PDMS backbone, the length of the PCL blocks, and the siloxane polymer level in
      the coating formulations. In addition to the siloxane libraries (3-aminopropyl
      terminated PDMS and poly(epsilon-caprolactone)-poly(dimethylsiloxane)
      poly(epsilon-caprolactone) (PCL-PDMS-PCL) triblock copolymers), the coating
      formulation included a trifunctional isocyanate crosslinker, trifunctional
      poly(epsilon-caprolactone) polyol, 2,4-pentanedione (pot-life extender),
      dibutyltin diacetate (catalyst), and a blend of solvents. The resulting coatings
      were analyzed for their surface energy and pseudobarnacle adhesion both before
      and after aging the coatings for 30 days in water. The water and methylene iodide
      contact angle averages increase with increasing molecular weight of PDMS.
      Coatings prepared from PCL-PDMS-PCL triblock copolymers have lower surface
      energies than coatings prepared from 3-aminopropyl-terminated PDMS; however,
      lower pseudobarnacle adhesion results were obtained for the coatings prepared
      from 3-aminopropyl-terminated PDMS than coatings prepared from PCL-PDMS-PCL
      triblock copolymers. The siloxane polymer level in the coating formulations does
      not have a significant effect on the surface energy of the coatings, but it
      resulted in higher pseudobarnacle adhesion.

PMID- 17206847
TI  - The impact of dyskeratosis congenita mutations on the structure and dynamics of
      the human telomerase RNA pseudoknot domain.
AB  - The pseudoknot domain is a functionally crucial part of telomerase RNA and
      influences the activity and stability of the ribonucleoprotein complex. Autosomal
      dominant dyskeratosis congenita (DKC) is an inherited disease that is linked to
      mutations in telomerase RNA and impairs telomerase function. In this paper, we
      present a computational prediction of the influence of two base DKC mutations on
      the structure, dynamics, and stability of the pseudoknot domain. We use molecular
      dynamics simulations, MM-GBSA free energy calculations, static analysis, and
      melting simulations analysis. Our results show that the DKC mutations stabilize
      the hairpin form and destabilize the pseudoknot form of telomerase RNA. Moreover,
      the P3 region of the predicted DKC-mutated pseudoknot structure is unstable and
      fails to form as a defined helical stem. We directly compare our predictions with
      experimental observations by calculating the enthalpy of folding and melting
      profiles for each structure. The enthalpy values are in very good agreement with
      values determined by thermal denaturation experiments. The melting simulations
      and simulations at elevated temperatures show the existence of an intermediate
      structure, which involves the formation of two UU base pairs observed in the
      hairpin form of the pseudoknot domain.

PMID- 17206848
TI  - Protein architecture chronology deduced from structures of amino acid synthases.
AB  - Inferring the protein architecture chronology is one of central topics in origin
      of life study and has been given much attention. Based on an amino acid
      evolutionary model that late amino acids were bio-synthesized prior to early
      counterparts, we addressed the issue by examining the structures of amino acid
      synthases. Despite the limited structural information on amino acid synthases,
      our deduction revealed that alpha/beta was the oldest protein class, which is in
      good agreement with the prior fold-usage-based conclusion.

PMID- 17206849
TI  - Intrinsic disorder in the Protein Data Bank.
AB  - The Protein Data Bank (PDB) is the preeminent source of protein structural
      information. PDB contains over 32,500 experimentally determined 3-D structures
      solved using X-ray crystallography or nuclear magnetic resonance spectroscopy.
      Intrinsically disordered regions fail to form a fixed 3-D structure under
      physiological conditions. In this study, we compare the amino-acid sequences of
      proteins whose structures are determined by X-ray crystallography with the
      corresponding sequences from the Swiss-Prot database. The analyzed dataset
      includes 16,370 structures, which represent 18,101 PDB chains and 5,434 different
      proteins from 910 different organisms (2,793 eukaryotic, 2,109 bacterial, 288
      viral, and 244 archaeal). In this dataset, on average, each Swiss-Prot protein is
      represented by 7 PDB chains with 76% of the crystallized regions being
      represented by more than one structure. Intriguingly, the complete sequences of
      only approximately 7% of proteins are observed in the corresponding PDB
      structures, and only approximately 25% of the total dataset have >95% of their
      lengths observed in the corresponding PDB structures. This suggests that the vast
      majority of PDB proteins is shorter than their corresponding Swiss-Prot sequences
      and/or contain numerous residues, which are not observed in maps of electron
      density. To determine the prevalence of disordered regions in PDB, the residues
      in the Swiss-Prot sequences were grouped into four general categories, "Observed"
      (which correspond to structured regions), "Not observed" (regions with missing
      electron density, potentially disordered), "Uncharacterized," and "Ambiguous,"
      depending on their appearance in the corresponding PDB entries. This non
      redundant set of residues can be viewed as a 'fragment' or empirical domain
      database that contains a set of experimentally determined structured regions or
      domains and a set of experimentally verified disordered regions or domains. We
      studied the propensities and properties of residues in these four categories and
      analyzed their relations to the predictions of disorder using several algorithms.
      "Non-observed," "Ambiguous," and "Uncharacterized" regions were shown to possess
      the amino acid compositional biases typical of intrinsically disordered proteins.
      The application of four different disorder predictors (PONDR(R) VL-XT, VL3-BA,
      VSL1P, and IUPred) revealed that the vast majority of residues in the "Observed"
      dataset are ordered, and that the "Not observed" regions are mostly disordered.
      The "Uncharacterized" regions possess some tendency toward order, whereas the
      predictions for the short "Ambiguous" regions are really ambiguous. Long
      "Ambiguous" regions (>70 amino acid residues) are mostly predicted to be ordered,
      suggesting that they are likely to be "wobbly" domains. Overall, we showed that
      completely ordered proteins are not highly abundant in PDB and many PDB sequences
      have disordered regions. In fact, in the analyzed dataset approximately 10% of
      the PDB proteins contain regions of consecutive missing or ambiguous residues
      longer than 30 amino-acids and approximately 40% of the proteins possess short
      regions (> or =10 and < 30 amino-acid long) of missing and ambiguous residues.

PMID- 17206850
TI  - RUN-CBFbeta interaction in C. elegans: computational prediction and experimental
      verification.
AB  - The Runt domain proteins are eukaryotic transcription factors that regulate major
      developmental pathways. All members of this family contain a highly-conserved
      sequence-specific DNA binding domain: the Runt domain (RD). Structural and
      biochemical studies have shown that the Runt domain undergoes a conformational
      transition upon binding to DNA and that this process is regulated by an unrelated
      partner protein CBFbeta that enhances the DNA binding affinity of RD. Most of the
      reported studies on the Runt domain transcription factors were performed on
      proteins from mammals and Drosophila whereas very little has been known about the
      C. elegans RD protein, RUN, which provides the simplest model system for
      understanding the function of this class of transcription factors. We performed
      computational studies on RD domains from various species including C. elegans,
      Drosophila, and human, using the atom-atom contact surface area scoring method.
      The scoring analysis indicates that the DNA binding regulation of the C. elegans
      RD protein (CeRD) occurs via its interaction with a CBFbeta-like partner, as
      found for the human proteins, whereas a different mode of regulation may occur in
      the Drosophila system. Sequence, secondary structure and fold analyses of a
      putative CBFbeta protein identified in the C. elegans genome, CeCBFbeta, sharing
      a 22% identity with the human protein, predict a similar structure of this
      protein to that of the human CBFbeta protein. We produced the C. elegans proteins
      CeRD and CeCBFbeta in bacteria and confirmed their physical interaction as well
      as cross interactions with the corresponding human proteins. We also confirmed
      the structural similarity of CBFbeta and CeCBFbeta by circular dichroism
      analysis. The combined results suggest that a similar mechanism of regulation
      operates for the human and the C. elegans RD proteins despite the low sequence
      identity between their CBFbeta proteins and the evolutionary distance between the
      two systems.

PMID- 17206851
TI  - Monomeric creatine kinase aggregation and sodium dodecyl sulfate-cyclodextrin
      assisted refolding.
AB  - The monomeric state of creatine kinase (CK) was stably captured at the
      equilibrium state by employing cysteine residue modifications in the presence of
      a denaturant, and at a partially folded state. The partially folded monomeric CK
      (PF-CK) was aggregated with kinetic order, which was mainly caused by the
      hydrophobic surface interactions between the CK subunits. The artificial
      chaperone, described as a SDS-cyclodextrin, was applied to prevent aggregation as
      well as to refold the PF-CK: SDS treatment onto the monomeric CK can
      significantly block aggregation and can be successfully refolded in the solutions
      containing cyclodextrins and DTT. Three types of cyclodextrins such as alpha-,
      beta-, and gamma-cyclodextrins were applied to strip SDS from the enzyme
      molecule, and each kinetic course was measured. The intrinsic fluorescence
      changes showed that reactivation occurred and this accompanied the conformational
      changes. The size exclusion chromatography detected the variously trapped
      monomeric CKs such as the thiol residue modified PF-CK, the SDS-binding PF-CK,
      the cyclodextrin treated PF-CK, and the DTT treated SDS-binding PF-CK. Our study
      demonstrated monomer CK aggregation for the first time; we also demonstrated the
      complex reassociation of CK during refolding with the aid of the SDS
      cyclodextrin, and these pathways followed first-order kinetics.

PMID- 17206852
TI  - Conserved water molecular dynamics of the different X-ray structures of
      rusticyanin: an unique aquation potentiality of the ligand bonded Cu++ center.
AB  - The invariant water molecular interaction involving in the Rusticyanin of
      Thiobacillus ferrooxidans is thought to be important for its molecular
      complexation with other proteins at differential acidophilic situation. The
      comparative analysis of the different x-ray, energy minimized, and auto solvated
      structures of Rusticyanin revealed the presence of five specific invariant bound
      water molecules (among the approximately 150 water molecules per monomer) in the
      crystals. The five W 205, W 206, W 112, W 214, and W 221 water molecules (in
      Rusticyanin PDB code: 1RCY) were seem to be invariant in all the seven structures
      (PDB codes: 1RCY, 1A3Z, 1A8Z, 1E3O, 1GY1, 1GY2, 2CAL). Among the five conserved
      water molecules the W 221 (of 1 RCY or the equivalent water molecules in the
      other oxidized form of Rusticyanin structures) had endowed an interesting
      coordination potentiality to Cu(+2) ion during the energy minimization. The W 221
      was observed to approach toward the tetrahedrally bonded Cu(+2) ion through the
      opposite (or trans) route of metal-bonded Met 148. This direct water molecular
      coordination affected the tetrahedral geometry of Cu(+2) to trigonal bipyramidal.
      Presumably this structural dynamics at the Cu(+2) center could involve in the
      electron transport process during protein-protein complexation.

PMID- 17206853
TI  - A comparative molecular dynamics study of thermophilic and mesophilic
      ribonuclease HI enzymes.
AB  - We studied a pair of homologous thermophilic and mesophilic ribonuclease HI
      enzymes by molecular dynamics simulations. Each protein was subjected to three 5
      ns simulations in explicit water at both 310 K and 340 K. The thermophilic enzyme
      showed larger overall positional fluctuations at both temperatures, while only
      the mesophilic enzyme at the higher temperature showed significant instability.
      When the temperature is changed, the relative flexibility of different local
      segments on the two proteins changed differently. Principal component analysis
      showed that the simulations of the two proteins explored largely overlapping
      regions in the conformational space. However, at 340 K, the collective structure
      variations of the thermophilic protein are different from those of the mesophilic
      protein. Our results, although not in accordance with the view that
      hyperthermostability of proteins may originate from their conformational
      rigidity, are consistent with several recent experimental and simulation studies
      which showed that thermophilic proteins may be conformationally more flexible
      than their mesophilic counterparts. The decorrelation between conformational
      rigidity and hyperthermostability may be attributed to the temperature dependence
      and long range nature of electrostatic interactions that play more important
      roles in the structural stability of thermophilic proteins.

PMID- 17206854
TI  - Domain analysis of fatty acid synthase protein (NP_217040) from Mycobacterium
      tuberculosis H37Rv--a bioinformatics study.
AB  - Different domains of fatty acid synthase (FAS) protein of Mycobacterium
      tuberculosis H37Rv, involved in mycolic acid synthesis were analyzed using
      various bioinformatics tools. Based on different database searches (CDD and
      Pfam), FAS protein of Mycobacterium tuberculosis was grouped into eight domains,
      five of which showed close similarity with pdb templates (1MLA, 1IQ6A, 2BMOA, and
      1J3NA). Based on the PSI blast analysis, 3D structures of only five domains were
      predicted using MODELLER software, and loop modeling was done for only those
      regions that were predicted as loops by predict protein server. Compared to the
      original structure, the loop modeled structure showed a lower DOPE score value
      for FAS protein. The X-ray determined templates that were used for predicting the
      3D structure suggest that, FAS protein has "Malonyl-coenzyme A-Hydratase
      Nitrobenzene dioxygenase-3-oxoacyl-(acp) synthase" activity. Accuracy of the
      prediction of 3D structure of different domains of FAS protein was further
      validated by Ramachandran plot and PROCHECK (G-value).

PMID- 17206855
TI  - The coiled-coil structure potential of the laminin LCC domain is very fragmented
      and does not differentiate between natural and non-detected isoforms.
AB  - There are 15 known laminins, which differ in the isoforms of the three chains
      that assemble into the cross-shape molecules that are observed by electron
      microscopy. The amino acid sequences of the rod-like portion of the long arm have
      long been recognized as having a potential for coiled-coil structure formation;
      however, an experimental determination of its structure is hampered by the
      complexity of laminin, a multidomain, heterotrimeric, and glycosilated 800 kDa
      molecule. Here, we have investigated the coiled-coil structure potential of
      laminin to evaluate its distribution along the long arm, the presence of
      conserved patterns, and differences between natural and non-natural isoforms.
      With these aims, we have analysed the sequences of each laminin chain in the
      context of the three-chain assemblies to yield an overall score of coiled-coil
      potential for the 15 natural laminins and for the other 30 possible but non
      detected ones. The potential has been calculated with two different existing
      methods to exclude algorithm specific biases and with different chain alignments
      to evaluate the dependency of the results on uncertainties in the specific
      alignment along the domain. The analysis shows that the distribution of the
      potential is discontinuous, highly fragmented along the arm, without a common
      pattern except for a higher potential at the C-terminus, and that natural and non
      natural laminins cannot be distinguished based on their coiled-coil potential,
      indicating that other factors are responsible for the selection of chain
      assembly.

PMID- 17206856
TI  - Study and prediction of secondary structure for membrane proteins.
AB  - In this paper we present a novel approach to membrane protein secondary structure
      prediction based on the statistical stepwise discriminant analysis method. A new
      aspect of our approach is the possibility to derive physical-chemical properties
      that may affect the formation of membrane protein secondary structure. The
      certain physical-chemical properties of protein chains can be used to clarify the
      formation of the secondary structure types under consideration. Another aspect of
      our approach is that the results of multiple sequence alignment, or the other
      kinds of sequence alignment, are not used in the frame of the method. Using our
      approach, we predicted the formation of three main secondary structure types
      (alpha-helix, beta-structure and coil) with high accuracy, that is Q(3) = 76%.
      Predicting the formation of alpha-helix and non-alpha-helix states we reached the
      accuracy which was measured as Q(2) = 86%. Also we have identified certain
      protein chain properties that affect the formation of membrane protein secondary
      structure. These protein properties include hydrophobic properties of amino acid
      residues, presence of Gly, Ala and Val amino acids, and the location of protein
      chain end.

PMID- 17206858
TI  - A Philadelphia fable: how ideal occlusion became the philosopher's stone of
      orthodontics.

PMID- 17206860
TI  - A phylogenomic study of human, dog, and mouse.
AB  - In recent years the phylogenetic relationship of mammalian orders has been
      addressed in a number of molecular studies. These analyses have frequently
      yielded inconsistent results with respect to some basal ordinal relationships.
      For example, the relative placement of primates, rodents, and carnivores has
      differed in various studies. Here, we attempt to resolve this phylogenetic
      problem by using data from completely sequenced nuclear genomes to base the
      analyses on the largest possible amount of data. To minimize the risk of
      reconstruction artifacts, the trees were reconstructed under different criteria
      distance, parsimony, and likelihood. For the distance trees, distance metrics
      that measure independent phenomena (amino acid replacement, synonymous
      substitution, and gene reordering) were used, as it is highly improbable that all
      of the trees would be affected the same way by any reconstruction artifact. In
      contradiction to the currently favored classification, our results based on full
      genome analysis of the phylogenetic relationship between human, dog, and mouse
      yielded overwhelming support for a primate-carnivore clade with the exclusion of
      rodents.

PMID- 17206861
TI  - Modeling HER2 effects on cell behavior from mass spectrometry phosphotyrosine
      data.
AB  - Cellular behavior in response to stimulatory cues is governed by information
      encoded within a complex intracellular signaling network. An understanding of how
      phenotype is determined requires the distributed characterization of signaling
      processes (e.g., phosphorylation states and kinase activities) in parallel with
      measures of resulting cell function. We previously applied quantitative mass
      spectrometry methods to characterize the dynamics of tyrosine phosphorylation in
      human mammary epithelial cells with varying human epidermal growth factor
      receptor 2 (HER2) expression levels after treatment with epidermal growth factor
      (EGF) or heregulin (HRG). We sought to identify potential mechanisms by which
      changes in tyrosine phosphorylation govern changes in cell migration or
      proliferation, two behaviors that we measured in the same cell system. Here, we
      describe the use of a computational linear mapping technique, partial least
      squares regression (PLSR), to detail and characterize signaling mechanisms
      responsible for HER2-mediated effects on migration and proliferation. PLSR model
      analysis via principal component inner products identified phosphotyrosine
      signals most strongly associated with control of migration and proliferation, as
      HER2 expression or ligand treatment were individually varied. Inspection of these
      signals revealed both previously identified and novel pathways that correlate
      with cell behavior. Furthermore, we isolated elements of the signaling network
      that differentially give rise to migration and proliferation. Finally, model
      analysis identified nine especially informative phosphorylation sites on six
      proteins that recapitulated the predictive capability of the full model. A model
      based on these nine sites and trained solely on data from a low HER2-expressing
      cell line a priori predicted migration and proliferation in a HER2-overexpressing
      cell line. We identify the nine signals as a "network gauge," meaning that when
      interrogated together and integrated according to the quantitative rules of the
      model, these signals capture information content in the network sufficiently to
      predict cell migration and proliferation under diverse ligand treatments and
      receptor expression levels. Examination of the network gauge in the context of
      previous literature indicates that endocytosis and activation of phosphoinositide
      3-kinase (PI3K)-mediated pathways together represent particularly strong loci for
      the integration of the multiple pathways mediating HER2's control of mammary
      epithelial cell proliferation and migration. Thus, a PLSR modeling approach
      reveals critical signaling processes regulating HER2-mediated cell behavior.

PMID- 17206862
TI  - Viral and cell cycle-regulated kinases in cytomegalovirus-induced pseudomitosis
      and replication.
AB  - A process of pseudomitosis occurs during human cytomegalovirus infection that
      appears similar to cellular mitosis but involves the formation of multiple
      spindle poles, abnormal condensation, and mislocalization of chromosomal DNA. The
      relationship of this process to viral replication and cell cycle regulation
      during infection has been poorly understood. Pseudomitosis consistently peaks at
      late times of infection in all viral strains examined but at overall highest
      frequencies (30% to 35% of cells) using one common laboratory strain variant
      (AD169varATCC). Cyclin-dependent kinase 1 (Cdk1) plays a crucial role in
      pseudomitosis, mirroring its role in conventional mitosis. Dominant negative Cdk1
      inhibits and wild-type Cdk1 stimulates this process; however, viral yields remain
      the same regardless of pseudomitosis levels. Broad inhibition of cell cycle
      regulated kinases (Cdk1/Cdk2/Cdk5/Cdk9) with indirubin-3'-monoxime substantially
      decreases viral yields and synergizes with the viral UL97 kinase inhibitor,
      maribavir. Thus, Cdk1 is necessary and sufficient to drive pseudomitosis, whereas
      a combination of viral and cell cycle-regulated kinases is important during viral
      replication.

PMID- 17206863
TI  - Early history of mammals is elucidated with the ENCODE multiple species
      sequencing data.
AB  - Understanding the early evolution of placental mammals is one of the most
      challenging issues in mammalian phylogeny. Here, we addressed this question by
      using the sequence data of the ENCODE consortium, which include 1% of mammalian
      genomes in 18 species belonging to all main mammalian lineages. Phylogenetic
      reconstructions based on an unprecedented amount of coding sequences taken from
      218 genes resulted in a highly supported tree placing the root of Placentalia
      between Afrotheria and Exafroplacentalia (Afrotheria hypothesis). This topology
      was validated by the phylogenetic analysis of a new class of genomic phylogenetic
      markers, the conserved noncoding sequences. Applying the tests of alternative
      topologies on the coding sequence dataset resulted in the rejection of the
      Atlantogenata hypothesis (Xenarthra grouping with Afrotheria), while this test
      rejected the second alternative scenario, the Epitheria hypothesis (Xenarthra at
      the base), when using the noncoding sequence dataset. Thus, the two datasets
      support the Afrotheria hypothesis; however, none can reject both of the remaining
      topological alternatives.

PMID- 17206864
TI  - A high-resolution map of segmental DNA copy number variation in the mouse genome.
AB  - Submicroscopic (less than 2 Mb) segmental DNA copy number changes are a recently
      recognized source of genetic variability between individuals. The biological
      consequences of copy number variants (CNVs) are largely undefined. In some cases,
      CNVs that cause gene dosage effects have been implicated in phenotypic variation.
      CNVs have been detected in diverse species, including mice and humans. Published
      studies in mice have been limited by resolution and strain selection. We chose to
      study 21 well-characterized inbred mouse strains that are the focus of an
      international effort to measure, catalog, and disseminate phenotype data. We
      performed comparative genomic hybridization using long oligomer arrays to
      characterize CNVs in these strains. This technique increased the resolution of
      CNV detection by more than an order of magnitude over previous methodologies. The
      CNVs range in size from 21 to 2,002 kb. Clustering strains by CNV profile
      recapitulates aspects of the known ancestry of these strains. Most of the CNVs
      (77.5%) contain annotated genes, and many (47.5%) colocalize with previously
      mapped segmental duplications in the mouse genome. We demonstrate that this
      technique can identify copy number differences associated with known polymorphic
      traits. The phenotype of previously uncharacterized strains can be predicted
      based on their copy number at these loci. Annotation of CNVs in the mouse genome
      combined with sequence-based analysis provides an important resource that will
      help define the genetic basis of complex traits.

PMID- 17206865
TI  - A role for Alstrom syndrome protein, alms1, in kidney ciliogenesis and cellular
      quiescence.
AB  - Premature truncation alleles in the ALMS1 gene are a frequent cause of human
      Alstrom syndrome. Alstrom syndrome is a rare disorder characterized by early
      obesity and sensory impairment, symptoms shared with other genetic diseases
      affecting proteins of the primary cilium. ALMS1 localizes to centrosomes and
      ciliary basal bodies, but truncation mutations in Alms1/ALMS1 do not preclude
      formation of cilia. Here, we show that in vitro knockdown of Alms1 in mice causes
      stunted cilia on kidney epithelial cells and prevents these cells from increasing
      calcium influx in response to mechanical stimuli. The stunted-cilium phenotype
      can be rescued with a 5' fragment of the Alms1 cDNA, which resembles disease
      associated alleles. In a mouse model of Alstrom syndrome, Alms1 protein can be
      stably expressed from the mutant allele and is required for cilia formation in
      primary cells. Aged mice developed specific loss of cilia from the kidney
      proximal tubules, which is associated with foci of apoptosis or proliferation. As
      renal failure is a common cause of mortality in Alstrom syndrome patients, we
      conclude that this disease should be considered as a further example of the class
      of renal ciliopathies: wild-type or mutant alleles of the Alstrom syndrome gene
      can support normal kidney ciliogenesis in vitro and in vivo, but mutant alleles
      are associated with age-dependent loss of kidney primary cilia.

PMID- 17206866
TI  - The astrocyte as a gatekeeper of synaptic information transfer.
AB  - We present a simple biophysical model for the coupling between synaptic
      transmission and the local calcium concentration on an enveloping astrocytic
      domain. This interaction enables the astrocyte to modulate the information flow
      from presynaptic to postsynaptic cells in a manner dependent on previous activity
      at this and other nearby synapses. Our model suggests a novel, testable
      hypothesis for the spike timing statistics measured for rapidly firing cells in
      culture experiments.

PMID- 17206867
TI  - Thermodynamically equivalent silicon models of voltage-dependent ion channels.
AB  - We model ion channels in silicon by exploiting similarities between the
      thermodynamic principles that govern ion channels and those that govern
      transistors. Using just eight transistors, we replicate--for the first time in
      silicon--the sigmoidal voltage dependence of activation (or inactivation) and the
      bell-shaped voltage-dependence of its time constant. We derive equations
      describing the dynamics of our silicon analog and explore its flexibility by
      varying various parameters. In addition, we validate the design by implementing a
      channel with a single activation variable. The design's compactness allows tens
      of thousands of copies to be built on a single chip, facilitating the study of
      biologically realistic models of neural computation at the network level in
      silicon.

PMID- 17206868
TI  - Spatiotemporal conversion of auditory information for cochleotopic mapping.
AB  - Auditory communication signals such as monkey calls are complex FM vocal sounds
      and in general induce action potentials in different timing in the primary
      auditory cortex. Delay line scheme is one of the effective ways for detecting
      such neuronal timing. However, the scheme is not straightforwardly applicable if
      the time intervals of signals are beyond the latency time of delay lines. In
      fact, monkey calls are often expressed in longer time intervals (hundreds of
      milliseconds to seconds) and are beyond the latency times observed in the brain
      (less than several hundreds of milliseconds). Here, we propose a cochleotopic map
      similar to that in vision known as a retinotopic map. We show that information
      about monkey calls could be mapped on a cochleotopic cortical network as
      spatiotemporal firing patterns of neurons, which can then be decomposed into
      simple (linearly sweeping) FM components and integrated into unified percepts by
      higher cortical networks. We suggest that the spatiotemporal conversion of
      auditory information may be essential for developing the cochleotopic map, which
      could serve as the foundation for later processing, or monkey call identification
      by higher cortical areas.

PMID- 17206869
TI  - Reducing the variability of neural responses: a computational theory of spike
      timing-dependent plasticity.
AB  - Experimental studies have observed synaptic potentiation when a presynaptic
      neuron fires shortly before a postsynaptic neuron and synaptic depression when
      the presynaptic neuron fires shortly after. The dependence of synaptic modulation
      on the precise timing of the two action potentials is known as spike-timing
      dependent plasticity (STDP). We derive STDP from a simple computational
      principle: synapses adapt so as to minimize the postsynaptic neuron's response
      variability to a given presynaptic input, causing the neuron's output to become
      more reliable in the face of noise. Using an objective function that minimizes
      response variability and the biophysically realistic spike-response model of
      Gerstner (2001), we simulate neurophysiological experiments and obtain the
      characteristic STDP curve along with other phenomena, including the reduction in
      synaptic plasticity as synaptic efficacy increases. We compare our account to
      other efforts to derive STDP from computational principles and argue that our
      account provides the most comprehensive coverage of the phenomena. Thus,
      reliability of neural response in the face of noise may be a key goal of
      unsupervised cortical adaptation.

PMID- 17206870
TI  - Fast population coding.
AB  - Uncertainty coming from the noise in its neurons and the ill-posed nature of many
      tasks plagues neural computations. Maybe surprisingly, many studies show that the
      brain manipulates these forms of uncertainty in a probabilistically consistent
      and normative manner, and there is now a rich theoretical literature on the
      capabilities of populations of neurons to implement computations in the face of
      uncertainty. However, one major facet of uncertainty has received comparatively
      little attention: time. In a dynamic, rapidly changing world, data are only
      temporarily relevant. Here, we analyze the computational consequences of encoding
      stimulus trajectories in populations of neurons. For the most obvious, simple,
      instantaneous encoder, the correlations induced by natural, smooth stimuli
      engender a decoder that requires access to information that is nonlocal both in
      time and across neurons. This formally amounts to a ruinous representation. We
      show that there is an alternative encoder that is computationally and
      representationally powerful in which each spike contributes independent
      information; it is independently decodable, in other words. We suggest this as an
      appropriate foundation for understanding time-varying population codes.
      Furthermore, we show how adaptation to temporal stimulus statistics emerges
      directly from the demands of simple decoding.

PMID- 17206871
TI  - The basal ganglia and cortex implement optimal decision making between
      alternative actions.
AB  - Neurophysiological studies have identified a number of brain regions critically
      involved in solving the problem of action selection or decision making. In the
      case of highly practiced tasks, these regions include cortical areas hypothesized
      to integrate evidence supporting alternative actions and the basal ganglia,
      hypothesized to act as a central switch in gating behavioral requests. However,
      despite our relatively detailed knowledge of basal ganglia biology and its
      connectivity with the cortex and numerical simulation studies demonstrating
      selective function, no formal theoretical framework exists that supplies an
      algorithmic description of these circuits. This article shows how many aspects of
      the anatomy and physiology of the circuit involving the cortex and basal ganglia
      are exactly those required to implement the computation defined by an
      asymptotically optimal statistical test for decision making: the multihypothesis
      sequential probability ratio test (MSPRT). The resulting model of basal ganglia
      provides a new framework for understanding the computation in the basal ganglia
      during decision making in highly practiced tasks. The predictions of the theory
      concerning the properties of particular neuronal populations are validated in
      existing experimental data. Further, we show that this neurobiologically grounded
      implementation of MSPRT outperforms other candidates for neural decision making,
      that it is structurally and parametrically robust, and that it can accommodate
      cortical mechanisms for decision making in a way that complements those in basal
      ganglia.

PMID- 17206872
TI  - Realistically coupled neural mass models can generate EEG rhythms.
AB  - We study the generation of EEG rhythms by means of realistically coupled neural
      mass models. Previous neural mass models were used to model cortical voxels and
      the thalamus. Interactions between voxels of the same and other cortical areas
      and with the thalamus were taken into account. Voxels within the same cortical
      area were coupled (short-range connections) with both excitatory and inhibitory
      connections, while coupling between areas (long-range connections) was considered
      to be excitatory only. Short-range connection strengths were modeled by using a
      connectivity function depending on the distance between voxels. Coupling strength
      parameters between areas were defined from empirical anatomical data employing
      the information obtained from probabilistic paths, which were tracked by water
      diffusion imaging techniques and used to quantify white matter tracts in the
      brain. Each cortical voxel was then described by a set of 16 random differential
      equations, while the thalamus was described by a set of 12 random differential
      equations. Thus, for analyzing the neuronal dynamics emerging from the
      interaction of several areas, a large system of differential equations needs to
      be solved. The sparseness of the estimated anatomical connectivity matrix reduces
      the number of connection parameters substantially, making the solution of this
      system faster. Simulations of human brain rhythms were carried out in order to
      test the model. Physiologically plausible results were obtained based on this
      anatomically constrained neural mass model.

PMID- 17206873
TI  - Dimension selection for feature selection and dimension reduction with principal
      and independent component analysis.
AB  - This letter is concerned with the problem of selecting the best or most
      informative dimension for dimension reduction and feature extraction in high
      dimensional data. The dimension of the data is reduced by principal component
      analysis; subsequent application of independent component analysis to the
      principal component scores determines the most nongaussian directions in the
      lower-dimensional space. A criterion for choosing the optimal dimension based on
      bias-adjusted skewness and kurtosis is proposed. This new dimension selector is
      applied to real data sets and compared to existing methods. Simulation studies
      for a range of densities show that the proposed method performs well and is more
      appropriate for nongaussian data than existing methods.

PMID- 17206874
TI  - One-bit-matching theorem for ICA, convex-concave programming on polyhedral set,
      and distribution approximation for combinatorics.
AB  - According to the proof by Liu, Chiu, and Xu (2004) on the so-called one-bit
      matching conjecture (Xu, Cheung, and Amari, 1998a), all the sources can be
      separated as long as there is an one-to-one same-sign correspondence between the
      kurtosis signs of all source probability density functions (pdf's) and the
      kurtosis signs of all model pdf's, which is widely believed and implicitly
      supported by many empirical studies. However, this proof is made only in a weak
      sense that the conjecture is true when the global optimal solution of an
      independent component analysis criterion is reached. Thus, it cannot support the
      successes of many existing iterative algorithms that usually converge at one of
      the local optimal solutions. This article presents a new mathematical proof that
      is obtained in a strong sense that the conjecture is also true when any one of
      local optimal solutions is reached in helping to investigating convex-concave
      programming on a polyhedral set. Theorems are also provided not only on partial
      separation of sources when there is a partial matching between the kurtosis
      signs, but also on an interesting duality of maximization and minimization on
      source separation. Moreover, corollaries are obtained on an interesting duality,
      with supergaussian sources separated by maximization and subgaussian sources
      separated by minimization. Also, a corollary is obtained to confirm the symmetric
      orthogonalization implementation of the kurtosis extreme approach for separating
      multiple sources in parallel, which works empirically but lacks mathematical
      proof. Furthermore, a linkage has been set up to combinatorial optimization from
      a distribution approximation perspective and a Stiefel manifold perspective, with
      algorithms that guarantee convergence as well as satisfaction of constraints.

PMID- 17206875
TI  - Boundedness and stability for integrodifferential equations modeling neural field
      with time delay.
AB  - In this letter, delayed integrodifferential equations modeling neural field
      (DIEMNF) is studied. The model of DIEMNF is first established as a modified
      neural field model. Second, it has been proved that if the interconnection of
      neural field is symmetric, then every trajectory of the system converges to an
      equilibrium. The boundedness condition for integrodifferential equations modeling
      neural field with delay is obtained. Moreover, when the interconnection is
      asymmetric, we give a sufficient condition that can guarantee that the
      equilibrium of the DIEMNF is unique and is also a global attractor.

PMID- 17206876
TI  - Providing the evidence for evidenced-based practice.

PMID- 17206877
TI  - Evaluating psychiatric hospital admission decisions for children in foster care:
      an optimal classification tree analysis.
AB  - This study explored clinical and nonclinical predictors of inpatient hospital
      admission decisions across a sample of children in foster care over 4 years (N =
      13,245). Forty-eight percent of participants were female and the mean age was
      13.4 (SD = 3.5 years). Optimal data analysis (Yarnold & Soltysik, 2005) was used
      to construct a nonlinear classification tree model for predicting admission
      decisions. As expected, clinical variables such as suicidality, psychoticism, and
      dangerousness predicted psychiatric admissions; however, several variables that
      are not direct indications of acute psychiatric distress, such as the presence of
      family problems and the location of the hospital screening, impacted decision
      making in a subsample of cases. Further analyses indicated that the model
      developed in Year 1 reliably and consistently predicted admission decisions (with
      64%-68% overall accuracy) across the next 3 years. Policy, research, and clinical
      implications are discussed.

PMID- 17206878
TI  - Psychometric properties of the Alabama parenting questionnaire-preschool
      revision.
AB  - The psychometric properties of the Alabama Parenting Questionnaire-Preschool
      Revision (APQ-PR) were explored in a sample of hyperactive-inattentive preschool
      children (N = 47) and nonimpaired controls (N = 113). A subset of parents
      completed the questionnaire on 2 occasions, approximately 1 year apart. Factor
      analysis revealed a 3-factor solution, accounting for 32.28% of the variance. The
      resultant Positive Parenting, Negative/Inconsistent Parenting, and Punitive
      Parenting factors demonstrated good internal consistency and temporal stability.
      At baseline, parents of hyperactive-inattentive and control children did not
      differ on any APQ-PR subscale. However, over time parents of controls increased
      their use of positive parenting techniques, whereas the use of positive parenting
      practices decreased over time in the hyperactive-inattentive group.

PMID- 17206879
TI  - Concurrent validity and clinical usefulness of several individually administered
      tests of children's social-emotional cognition.
AB  - In this study, the validity of 5 tests of children's social-emotional cognition,
      defined as their encoding, memory, and interpretation of social information, was
      tested. Participants were 126 clinic-referred children between the ages of 5 and
      17. All 5 tests were evaluated in terms of their (a) concurrent validity, (b)
      incremental validity, and (c) clinical usefulness in predicting social
      functioning. Tests included measures of nonverbal sensitivity, social language,
      and social problem solving. Criterion measures included parent and teacher report
      of social functioning. Analyses support the concurrent validity of all measures,
      and the incremental validity and clinical usefulness of tests of pragmatic
      language and problem solving.

PMID- 17206880
TI  - Parents' aggressive influences and children's aggressive problem solutions with
      peers.
AB  - This study examined children's aggressive and assertive solutions to hypothetical
      peer scenarios in relation to parents' responses to similar hypothetical social
      scenarios and parents' actual marital aggression. The study included 118 children
      ages 9 to 10 years old and their mothers and fathers. Children's aggressive
      solutions correlated with same-sex parents' actual marital aggression. For
      children with mothers who exhibited low actual marital aggression, mothers'
      aggressive solutions to hypothetical situations corresponded with children's
      tendencies to propose aggressive but not assertive solutions. In a 3-way
      interaction, fathers' aggressive solutions to peer scenarios and marital
      aggression, combined, exacerbated girls' aggressive problem solving but had the
      opposite effect for boys. We address the complexity, particularly with respect to
      parent and child gender combinations, in understanding parents' aggressive
      influences on children's peer relationships.

PMID- 17206881
TI  - Subtypes of rumination in adolescence: associations between brooding, reflection,
      depressive symptoms, and coping.
AB  - Prior research has indicated that rumination contributes to the maintenance or
      intensification of depressive symptoms among adults. This study examined
      associations between rumination and depressive symptoms in early adolescence.
      Using a short-term longitudinal design, we evaluated relations between subtypes
      of rumination and both depressive symptoms and coping among a community sample of
      168 adolescents (70 boys, 98 girls, age M= 13.58). Results provided support for
      brooding and self-reflective subtypes of rumination. Brooding, but not
      reflection, predicted the development of depressive symptoms over time,
      particularly for girls. Brooding was related to maladaptive disengagement coping
      strategies, whereas reflection was related to adaptive primary and secondary
      coping strategies. These results suggest that not all types of self-focus on
      emotion contribute to the maintenance or intensification of depressive symptoms.

PMID- 17206882
TI  - Rumination on anger and sadness in adolescence: fueling of fury and deepening of
      despair.
AB  - We examined anger rumination and sadness rumination in clinic-referred
      adolescents (N = 121). Factor analysis indicated that items from analogous anger
      and sadness rumination measures loaded onto 2 factors tapping anger rumination
      and sadness rumination, respectively. Structural equation modeling confirmed
      unique relations between each form of rumination and specific emotional or
      behavioral problems. Anger and anger rumination were independent predictors of
      aggression, suggesting that both the affective component of anger (i.e., angry
      feelings) and the cognitive process (i.e., recurrent thoughts about anger) are
      important in predicting aggressive behavior. Girls reported higher levels of both
      forms of rumination compared to boys; however, no sex differences were found in
      the relations between either form of rumination and outcomes.

PMID- 17206883
TI  - Sociocultural influences and body image in 9- to 12-year-old girls: the role of
      appearance schemas.
AB  - This study tested whether an individual's beliefs about the importance of
      appearance in their life is a mediator of sociocultural influences on body
      dissatisfaction in young girls. Participants were 265 girls in Grades 4 to 7 (M
      age = 10.71 years) from 5 private primary schools in metropolitan Adelaide, South
      Australia. Girls completed questionnaire measures of appearance television and
      magazine exposure, peer appearance conversations, autonomy, appearance schemas,
      and body dissatisfaction. Appearance media exposure and peer appearance
      conversations were negatively related to body esteem, and autonomy positively
      predicted body esteem. Most important, appearance schemas mediated between all
      sociocultural variables and body dissatisfaction.

PMID- 17206884
TI  - Longitudinal associations between externalizing behavior and dysfunctional eating
      attitudes and behaviors: a community-based study.
AB  - This study investigated longitudinal associations between externalizing behavior
      and dysfunctional eating attitudes and behaviors. Participants were girls drawn
      from the community-based Minnesota Twin Family Study and assessed at ages 11, 14,
      and 17. Cross-sectional correlations indicated that the strength of the
      associations between externalizing behavior and dysfunctional eating attitudes
      and behaviors increased over time. Mixed-model analyses indicated that earlier
      externalizing behavior predicted increases in weight preoccupation, body
      dissatisfaction, and use of inappropriate compensatory behaviors. Earlier use of
      inappropriate compensatory behaviors predicted increases in externalizing
      behavior.

PMID- 17206885
TI  - Overgeneral autobiographical memory and depressive disorder in children.
AB  - Overgeneral autobiographical memory seems to be a stable cognitive marker in
      depressed adults and may predict persistence of depression. This study
      investigated whether depressive disorders in children are associated with
      overgeneral memory. Sixty children (ages 9 to 13 years) participated; 15 were
      diagnosed with lifetime depressive disorder, 25 had other lifetime psychiatric
      disorders, and 20 had no history of psychiatric disorder. Depressed children gave
      fewer specific memories compared to children with no or other psychiatric
      disorders, even after controlling for depressive mood, potential traumatic life
      events, verbal IQ, and verbal memory.

PMID- 17206886
TI  - Reliability and validity of the youth version of the Balloon Analogue Risk Task
      (BART-Y) in the assessment of risk-taking behavior among inner-city adolescents.
AB  - This study examined the reliability and validity of the youth version of the
      Balloon Analogue Risk Task (BART-Y) for assessing adolescent risk behaviors among
      a sample of 98 inner-city African American adolescents (M age = 14.8, SD = 1.5).
      In addition to a relation with sensation seeking, BART-Y responding evidenced a
      significant relation with a composite of risk behaviors across substance use,
      sexual behavior, delinquency, and health domains. BART-Y responding also
      explained unique variance in a composite of these risk behaviors above and beyond
      demographic variables and risk-related personality constructs, including
      sensation seeking and impulsivity.

PMID- 17206887
TI  - Update on the epidemiology and biology of renal cortical neoplasms.
AB  - A new era is developing in the understanding of the diagnosis, classification,
      and management of renal-cell carcinoma (RCC). Historically, RCC has been divided
      into subtypes on the basis of the histopathologic findings alone. Now, genetic
      alterations, nuclear characteristics, and clinical criteria are routinely
      incorporated into the classification. The greater use of axial imaging that began
      in the 1980s dramatically increased the incidence of RCC, but there has not been
      a decrease in the percentage of cases that are metastatic. Nevertheless, many
      incidental lesions prove to be benign, so there is renewed enthusiasm for biopsy
      before treatment is selected. Genetic conditions associated with RCC, such as Von
      Hippel Lindau and Birt-Hogg-Dube syndromes, along with genetic analyses of
      tumors, have provided considerable insight into the pathogenesis of these
      lesions. Renal-cell carcinoma is resistant to chemotherapy, and high-dose
      interleukin-2 is the only regimen currently approved by the Food and Drug
      Administration for the treatment of advanced RCC. Stem cell transplantation is an
      evolving therapy. The vascular endothelial growth factor (VEGF), epidermal growth
      factor (EGF), platelet-derived growth factor (PDGF), and transforming growth
      factor-alpha pathways are promising targets for medical therapy of RCC.
      Bevacizumab, a monoclonal antibody that acts as a competitive blocker of the VEGF
      receptor; sorafenib, an oral well-tolerated tyrosine kinase inhibitor that blocks
      the intracellular second-messenger system associated with the VEGF receptor;
      sunitinib, a multitarget inhibitor of kinases associated with the VEGF and PDGF
      receptors; temsirolimus (CCI-779), a kinase blocker that inhibits the mammalian
      target of rapamycin pathway; and erlotinib, an inhibitor of the tyrosine kinases
      associated with the EGF receptor, have shown promise. Combinations of the above
      therapies and cytokines also are being investigated, as there may be synergistic
      effects.

PMID- 17206888
TI  - The da Vinci robot.
AB  - BACKGROUND: One might assume from the title of this paper that the nuances of a
      complex mechanical robot will be discussed, and this would be correct. On the
      other hand, the date of the design and possible construction of this robot was
      1495, a little more than five centuries ago. The key point in the title is the
      lack of a trademarked name, as Leonardo was the designer of this sophisticated
      system. His notes from the Codex Altanticus represent the foundation of this
      report. METHODS: English translations of da Vinci's notebooks are currently
      available. Beginning in the 1950s, investigators at the University of California
      began to ponder the significance of some of da Vinci's markings on what appeared
      to be technical drawings. Such markings also occur in his Codex Atlanticus (the
      largest single collection of da Vinci's sheets, consisting of 1119 separate pages
      and 481 folios) along with a large number of other mechanical devices. Continuing
      research at the Instituto e Museo di Storia della Scienza in Florence has yielded
      a great deal of information about Leonardo's intentions with regard to his
      mechanical knight. RESULTS: It is now known that da Vinci's robot would have had
      the outer appearance of a Germanic knight. It had a complex core of mechanical
      devices that probably was human powered. The robot had two independent operating
      systems. The first had three degree-of-freedom legs, ankles, knees, and hips. The
      second had four degrees of freedom in the arms with articulated shoulders,
      elbows, wrists, and hands. A mechanical analog-programmable controller within the
      chest provided the power and control for the arms. The legs were powered by an
      external crank arrangement driving the cable, which connected to key locations
      near each lower extremity's joints. Da Vinci also is known to have devised a
      programmable front-wheel-drive automobile with rack-and-pinion suspension
      mechanisms at age 26. He would recall this device again, when, at age 40, he is
      thought to have built a programmable automated lion, but by then, he had produced
      his own metal springs as well as drum-containing springs called tambours. He
      positioned his fusee to a stationary rotating power output shaft that would be
      used to power his programmable automaton. CONCLUSIONS: Part of the obscurity of
      da Vinci's robot comes from the difficulties interpreting Leonardo's markings.
      His designs precede any formal method of blueprint designing. The technical
      aspects had to be deciphered before anyone could even attempt to reproduce his
      intended device. This robotic device fits together with other pieces of evidence
      that link 15(th) Century automatons to da Vinci's design, namely the automated
      Tea Servers from Spain. As with many things from da Vinci, looking backward at
      this master leaves one with a pronounced sense of awe at his prescient view of
      the world.

PMID- 17206889
TI  - Percutaneous bladder cryoablation in porcine model.
AB  - PURPOSE: To demonstrate the morphologic changes of full-thickness bladder
      cryoablation utilizing contemporary percutaneous technology. MATERIALS AND
      METHODS: Cryoablation of the bladder wall was conducted in 24 pigs. The bladders
      were exposed laparoscopically and inspected cystoscopically. The animals
      underwent either extravesical (serosal) or transvesical (mucosal) approaches for
      the creation of the cryoablation lesion. Single or double freeze/thaw cycles were
      applied, and no bladder drainage was used. The bladder was evaluated for
      perforation, and histologic examination was undertaken to assess the extent of
      acute, subacute (2 weeks), or chronic (1 month) lesions. RESULTS: Cryoablation
      reliably produced a controlled transmural area of necrosis (both serosa and
      mucosa) by both techniques. The size and extent of the lesion were directly
      proportional to the duration of freezing and the type of cryoprobe used. The
      pathology report confirmed the full-thickness coagulative necrosis of muscle.
      Bladder perforation was not detected clinically or at autopsy. CONCLUSION:
      Cryoablation produces reliable zones of tissue destruction without bladder
      perforation. These preliminary data show the safety and feasibility for trials in
      the treatment of bladder tumors by laparoscopic, cystoscopic, or image-guided
      techniques.

PMID- 17206890
TI  - Fate of abstracts presented at the World Congress of Endourology: are they
      followed by publication in peer-reviewed journals?
AB  - PURPOSE: To estimate the acceptance rate of peer-reviewed journals, to describe
      the time course of subsequent full publication, and to identify those with
      characteristics associated with publication of the abstracts presented at the
      World Congress of Endourology (WCE). METHODS: All abstracts accepted for
      presentation at the 2001 and 2002 WCE meetings were identified from the published
      supplements to the Journal of Endourology. The subsequent publication rate for
      the corresponding studies was evaluated by scanning MEDLINE for the 5-year period
      after the meetings. RESULTS: Overall, 20.5% of the abstracts were followed by
      publication in peer-reviewed journals. Abstracts on transurethral, laparoscopic,
      and percutaneous procedures had the highest publication rates (25.5%, 25%, and
      24.3%, respectively). Studies from North America had the highest publication rate
      (29.2%). The mean time to publication was 14.6 months. There was an 80% chance
      that an eventually published abstract was in print 2 years after presentation.
      The largest number of the reports were published in the Journal of Endourology
      (75 of 234; 32%), the official publication of the society that sponsors the WCE.
      CONCLUSIONS: Only one fifth of the abstracts presented at the WCE are ultimately
      published in peer-reviewed journals. Attendees should be aware of this
      limitation, and scientific committees should be encouraged to be more selective.
      Although presentation at major urological congresses constitutes an invaluable
      method for rapid scientific dissemination, abstracts contain data that usually
      are difficult to access and of questionable validity. In this respect,
      investigators are encouraged to publish their data.

PMID- 17206891
TI  - Case report: scrotal ecchymosis after shockwave lithotripsy.
AB  - Shockwave lithotripsy (SWL) is the treatment of choice for most renal calculi
      because it is highly effective and relatively noninvasive. Although complications
      of SWL are relatively few, one that occurs more frequently is perirenal hematoma,
      usually diagnosed by radiologic procedures. We present an interesting case of
      scrotal ecchymosis as an unusual presentation of perirenal hematoma causing
      ipsilateral spermatic-vein thrombosis after SWL for a left renal stone. To our
      knowledge, this condition has not been reported previously.

PMID- 17206892
TI  - Renal tract calculi: comparison of stone size on plain radiography and
      noncontrast spiral CT scan.
AB  - BACKGROUND AND PURPOSE: Noncontrast spiral CT (NCCT) has emerged as the
      investigation of choice in patients presenting with renal-tract calculi. As
      management guidelines are based on stone size measured on plain radiography of
      the kidneys, ureters, and bladder (KUB), it is important to assess the accuracy
      of stone size measured on NCCT compared with KUB films. PATIENTS AND METHODS: The
      NCCT and KUB studies obtained from 24 patients (27 stones) presenting to the
      emergency department at a major metropolitan hospital were analyzed randomly and
      independently by two urologists and one uroradiologist. The NCCT scans were
      assessed separately from the KUB films. Only size in greatest dimension and stone
      location were recorded. RESULTS: The stone size was 2 to 38 mm on NCCT scans and
      2 to 46 mm on KUB films. The mean stone size was 6.773 +/- 6.146 mm and 7.747 +/-
      7.866 mm, respectively (P = 0.0398; Student's t-test). Almost three fourths (70%)
      of the stones were larger on KUB films than they were on NCCT scans, with a mean
      difference -0.974 mm (95% confidence interval -5.652, 3.703) for NCCT.
      CONCLUSION: Spiral CT underestimates stone size by approximately 12% compared
      with KUB films. This error may impact stone management as outlined in guidelines
      published by the American Urological Association, particularly for stones about 5
      mm in greatest dimension. These patients may initially be managed conservatively
      when intervention would be more appropriate.

PMID- 17206893
TI  - Use of tramadol drip in controlling renal colic pain.
AB  - BACKGROUND AND PURPOSE: Although the continuous perfusion of antispasmodic drugs
      has been the traditional mainstay in the treatment of renal colic, the results
      more often than not are unsatisfactory. Our hypothesis was that a continuous
      intravenous (IV) drip of tramadol would be an effective and safe alternative.
      PATIENTS AND METHODS: In this prospective study, 300 patients with renal colic
      were randomized into four treatment groups, single blind for the patients. At the
      start, all received an anti-inflammatory drug intramuscularly and an antiemetic
      and antispasmodic IV. Group A was given the classical IV antispasmodic perfusion
      combined with a sham drip. Group B received the classical antispasmodic perfusion
      in combination with a tramadol drip. Group C had a sham perfusion and drip. Group
      D received a sham perfusion and tramadol drip. There was no significant
      difference in the degree of pain between the groups on a visual analog scale
      (VAS) at the start. The pain was scored again on the VAS at 30 minutes, 1 hour,
      and 4 hours after the start of the treatment and at IV urography. Side effects,
      as well as the need for rescue medication, were registered. RESULTS: Both
      tramadol groups scored significantly better after 60 and 240 minutes and during
      IV urography (P < 0.005). There was a significant decrease in VAS in group B
      after 30 minutes. The tramadol groups needed significantly less rescue medication
      (P = 0.001). There was no significant difference in the reported side effects.
      The combination spasmolytic-tramadol drip scored the best, although the
      difference was not statistically significant. CONCLUSION: We consider our
      hypothesis proved that a continuous tramadol drip is a safe and valuable
      analgesic regimen in renal colic.

PMID- 17206894
TI  - Safety and efficacy of supracostal access in tubeless percutaneous
      nephrolithotomy.
AB  - PURPOSE: To evaluate the feasibility and safety of supracostal access in tubeless
      percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: From September 2004 to
      November 2005, tubeless PCNL using supracostal access was done for 72 patients at
      our institute. Patients requiring more than two percutaneous tracts or with
      significant intraoperative bleeding or residual stone burden were excluded from
      the study. The outcome of these patients was compared with that of a historic
      cohort of similar patients having supracostal access with routine placement of a
      nephrostomy tube. The two groups had comparable demographic data. RESULTS: The
      differences in the mean drop in hemoglobin concentration, transfusion
      requirement, and complication rate in the two groups were not statistically
      significant, with three patients in the study group and four patients in the
      control group requiring blood transfusion. Patients undergoing tubeless PCNL
      required less analgesia (P = 0.000) and were discharged a mean of 19 hours
      earlier (P = 0.000) than those in the control group. Complete stone clearance was
      achieved in 90.27% of the renal units in the study group and 86.11% of the renal
      units in the control group. Two patients in the study group and three patients in
      the control group had postoperative hydrothorax, all of whom, except for one in
      the control group, were managed conservatively. CONCLUSION: Supracostal access in
      tubeless PCNL appears to be feasible, safe, and effective, offering the
      advantages of a lower analgesic requirement and shorter hospital stay without
      increasing thoracic complications. Studies with larger numbers of patients are
      needed to confirm these initial findings.

PMID- 17206895
TI  - Ureteroscopic treatment of multiple distal-ureteral stones.
AB  - BACKGROUND AND PURPOSE: Ureteroscopic intracorporeal lithotripsy for solitary
      distal-ureteral stones may be considered a first-line therapy. However, few
      reports that mention ureteroscopic procedures for multiple ureteral stones were
      found in the literature. Retrospectively, we reviewed our patients who were
      treated by ureteroscopy for multiple distal-ureteral stones. PATIENTS AND
      METHODS: Fifteen patients underwent ureteroscopic pneumatic lithotripsy for
      unilateral multiple distal-ureteral stones. Ten patients had two stones, four
      patients had three stones, and another patient had five stones. The average stone
      number per ureteral unit was 2.44, and the average stone size was 9.7 mm (range 3
      23 mm). RESULTS: Eighty percent of the patients (12/15) who had unilateral stones
      were stone free after the first session of ureteroscopic pneumatic lithotripsy.
      Two patients underwent a second ureteroscopy procedure for the remaining stone or
      failure of ureteral access. Overall, 93.3% of the patients (14/15) were stone
      free. Ureteral perforation as a major complication occurred in one patient
      (6.6%), who was treated by open surgery. We did not routinely use Double-J
      ureteral stents after ureteroscopy. Only one patient required stenting because of
      failure of ureteral access. Steinstrasse was observed in three patients, but it
      resolved spontaneously in the early postoperative period. CONCLUSION:
      Ureteroscopic pneumatic lithotripsy has a high success rate with few
      complications for the treatment of unilateral multiple distal-ureteral stones.
      Ureteroscopic pneumatic lithotripsy seems very effective for such stones.

PMID- 17206896
TI  - Primary ureteroscopy for distal-ureteral stones compared with ureteroscopy after
      failed extracorporeal lithotripsy.
AB  - BACKGROUND AND PURPOSE: We reviewed our experiences with ureteroscopic pneumatic
      lithotripsy (URS-PL) for the treatment of distal-ureteral stones and investigated
      whether failed extracorporeal shockwave lithotripsy (SWL) is a limiting factor
      for the ureteroscopic procedure. PATIENTS AND METHODS: We retrospectively studied
      the medical records of 375 patients treated with URS-PL from January 1999 to
      September 2005 in our clinic. Of these patients, 213 were treated with URS-PL
      primarily (group 1), whereas the remaining 162 patients had undergone SWL
      unsuccessfully before URS-PL was performed (group 2). We used 9F or 9.5F rigid
      instruments and the Vibrolith (Elmed, Ankara, Turkey). RESULTS: In group 1, 206
      patients (96.7%) were treated successfully with URS alone, as were 155 patients
      (95.6%) in group 2. Impacted stones were observed in 21 patients in group 1
      (9.85%) and in 57 patients in group 2 (35.1%). The average operating time was
      33.19 +/- 9.039 minutes in group 1 and 57.42 +/- 8.757 minutes in group 2. The
      stone-free rates of the two groups were significantly different on the first
      postoperative day, but this difference decreased to an insignificant level at the
      end of the first month. CONCLUSION: When SWL fails, URS-PL is as safe and
      effective as primary URS. Pneumatic lithotripsy also seems to be effective for
      impacted stones.

PMID- 17206897
TI  - Acute effects of percutaneous tract dilation on renal function and structure.
AB  - BACKGROUND: Percutaneous nephrolithotomy (PCNL) is performed on a routine basis
      for the rapid and efficient removal of large caliceal stones. After percutaneous
      puncture, rigid dilators or an inflatable balloon are used to dilate the
      nephrostomy tract to allow access to the collecting system for stone removal.
      Little is known of the acute impact of tract dilation procedures on renal
      function. MATERIALS AND METHODS: We compared renal hemodynamic and excretory
      function in female pigs immediately before and up to 5 hours after percutaneous
      nephrostomy (PCN) using sequential Amplatz dilators (N = 8) or Nephromax balloon
      inflation (N = 7) and control pigs with no PCN access (N = 8). We also examined
      renal function in patients undergoing PCNL. RESULTS: The two PCN procedures
      produced a renal lesion of comparable size and morphology, as well as similar
      changes in renal function. Glomerular filtration rate (GFR), renal plasma flow
      (RPF), and urinary sodium excretion (U(Na)V) were significantly reduced in
      Amplatz- and Nephromax-treated kidneys throughout the 5-hour observation period,
      by about 50%, 60%, and 80%, respectively. In control pigs, GFR and RPF remained
      stable and U(Na)V declined progressively to about 50% of baseline over the course
      of the experiment. The contralateral kidney showed changes in renal function
      similar to those in the PCN-treated or control kidney in all three groups. A
      retrospective analysis of 196 adults with normal renal function who underwent
      unilateral PCNL using the Nephromax balloon dilator revealed a significant
      increase in serum creatinine of 0.14 mg/dL at 1 day. CONCLUSION: Both animal and
      human studies show that PCN is associated with an acute decline in renal
      function.

PMID- 17206898
TI  - Novel method used to test pullout parameters of different nephrostomy catheters.
AB  - PURPOSE: To present a novel in-vitro pig model for testing the design and
      function of different internal catheter constructs, along with the resulting exit
      wound resulting from removal. MATERIALS AND METHODS: We compared the pullout
      parameters of two nephrostomy catheters that differ only in their internal loop
      design. RESULTS: Greater force, work, and displacement are necessary to extricate
      catheters with a double loop without increasing exit-wound size. CONCLUSION:
      Although the differences were not statistically significant, results from this
      model have potential clinical implications that may prompt further design
      modifications and prototype development to improve the retention of catheters in
      the kidney, thus reducing patient discomfort and costs associated with repeated
      catheter placement.

PMID- 17206899
TI  - Forgotten, encrusted ureteral stents: a challenging problem with an endourologic
      solution.
AB  - BACKGROUND AND PURPOSE: Forgotten, encrusted ureteral stents represent a
      difficult problem for urologists, and a consensus on the best therapeutic
      approach is lacking. We present our experience with endoscopic management of this
      challenging problem and discuss the chosen treatment combinations. PATIENTS AND
      METHODS: Five women and four men aged 31 to 71 years (mean 50.2 years) with 10
      stents indwelling for 6 to 85 months (mean 24.1 months) were treated in our
      department. Stent encrustation and the associated stone burden were evaluated by
      plain radiographs and intravenous urography. Treatment decisions were based on
      the clinical presentation and imaging findings. Three stents in two patients had
      minimal or slight encrustations. RESULTS: The mean number of procedures per
      patient was 2.1 (range 1-4). Percutaneous nephrolithotomy was performed in eight
      patients and retrograde ureteroscopy with or without intracorporeal lithotripsy
      in seven cases. Cystolitholapaxy or percutaneous cystolithotripsy was used to
      manage the distal portion of the encrusted stent in two cases. Extracorporeal
      shockwave lithotripsy was performed in only two patients. All stents and the
      associated stones were eventually removed without any complications. CONCLUSIONS:
      Combined endourologic techniques can achieve safe removal of forgotten stents if
      treatment is tailored to the volume of encrustation and associated stone. Imaging
      evaluation and documentation of negative urine culture are imperative prior to
      any attempt to remove the stent.

PMID- 17206900
TI  - Laparoscopic transperitoneal dismembered pyeloplasty for ureteropelvic junction
      obstruction.
AB  - PURPOSE: To review the outcome of transperitoneal laparoscopic dismembered
      pyeloplasty (LDP) in our institution. PATIENTS AND METHODS: From April 2001 to
      April 2005, 36 men and 34 women underwent LDP for symptomatic and radiologically
      proved ureteropelvic junction (UPJ) obstruction. A successful outcome was defined
      clinically by improvement in symptoms and objectively by improvement in the
      diuretic renography study performed at 3 and 12 months after reconstruction.
      RESULTS: The mean operative time was 160.5 +/- 45 minutes with a mean blood loss
      of 77.8 +/- 52.8 mL. There were no conversions to open surgery. Lower-pole
      vessels were observed in 38 patients (54.3%). In all cases, the ureter was
      transposed anteriorly. The mean hospital stay was 3.3 +/- 2.1 days. Postoperative
      complications were recorded in 4 patients (5.7%). One patient developed an
      anastomotic stricture. A successful outcome was achieved in 68 of the 70 patients
      (97.1%) at a mean follow-up of 27.6 +/- 13.2 months. CONCLUSION: Our results
      further strengthen the evidence that LDP has a reliable medium-term outcome with
      the added benefit of being minimally invasive.

PMID- 17206901
TI  - Reported failures of the polymer self-locking (Hem-o-lok) clip: review of data
      from the Food and Drug Administration.
AB  - BACKGROUND AND PURPOSE: New technology has played an important role in the
      proliferation of laparoscopy within urology. A central issue remains meticulous
      hemostasis, particularly for larger vessels (e.g., renal artery and vein). This
      paper presents available information regarding failure of the widely utilized
      nonabsorbable polymer Hem-o-lok clip (Weck Closure Systems, Research Triangle
      Park, NC), introduced in 1999. METHODS: The Food and Drug Administration Center
      for Devices and Radiological Health maintains a compendium of reports of adverse
      events involving medical devices (MAUDE). We performed multiple searches of MAUDE
      using a variety of key words, including Weck, Hem-o-lok, laparoscopy,
      nephrectomy, and clip. RESULTS: Within the MAUDE database, we identified 27
      reports of problems with the Hem-o-lok clip until July 6, 2005. Of these events,
      only 1 (4%) involved application during open surgery, with the remainder
      occurring during laparoscopy. Minimal morbidity resulted from applicator
      difficulty during laparoscopic cholecystectomy (N = 7; 26%), with one case of
      open conversion. Forty-eight percent (N = 13) of the failures occurred during
      urologic laparoscopy; of these, bleeding was the primary problem in 77%. Delayed
      exploration, immediate open conversion, and death resulted in 38% (N = 5), 8% (N
      = 1), and 15% (N = 2), respectively. No clear etiology for the events could be
      found, although in all situations, multiple clips had been applied with apparent
      initial vessel control intraoperatively. CONCLUSIONS: Reported difficulty with
      the Hem-o-lok clip occurs primarily during laparoscopic surgery. Cases of failure
      after laparoscopic nephrectomy require urgent exploration, although it is unclear
      whether device or user error is the underlying cause. Regardless, care must be
      taken in securing the renal vessels, surgeons must be educated regarding proper
      use and techniques, and consideration should be given to using transfixing
      techniques.

PMID- 17206902
TI  - A 4-year review of balloon dilation of ureteral strictures in renal allografts.
AB  - BACKGROUND: Ureteral obstruction necessitating intervention occurs in 2% to 7.5%
      of all renal allograft recipients. Conventional management includes open surgical
      repair, although more recently, percutaneous ureteral dilation has been
      performed. PATIENTS AND METHODS: The management and outcome of all seven
      allograft ureteral strictures treated with balloon dilation in our unit over a 4
      year period were reviewed. Half (55%) of these strictures occurred in the
      proximal ureter. RESULTS: Four strictures were dilated successfully with a
      requirement for five dilations in total. These patients have stable graft
      function with no evidence of obstruction. Five strictures persisted despite 11
      dilations. There were no significant complications from balloon dilation.
      CONCLUSION: Definitive surgical management should be considered if obstruction
      persists after one attempt at ureteral dilation, as multiple dilations have a low
      success rate (25%).

PMID- 17206903
TI  - Ureteral injuries during gynecologic surgery: treatment with a minimally invasive
      approach.
AB  - PURPOSE: To report the safety and efficacy of percutaneous nephrostomy and
      primary antegrade recanalization for treatment of iatrogenic ureteral strictures
      after gynecologic surgery. PATIENTS AND METHODS: Ten women had symptoms
      suggestive of ureteral obstruction during the immediate postoperative period (5
      days-1 week after surgery). Under analgesia and conscious sedation, standard
      percutaneous nephrostomy was performed, and a long 7F sheath was placed in the
      upper ureter. The obstructions were traversed with the aid of a 0.0035-inch
      Glidewire and a 5F angled Glide catheter (Terumo, Japan). Subsequently, the areas
      were dilated with angioplasty balloons to a maximum diameter of 7 mm. Finally, an
      8F percutaneous internal/external nephroureteral drainage stent was inserted to
      secure ureteral patency. Follow-up was carried out by serial nephrostomography
      until removal of the stent and by renal ultrasonography thereafter. RESULTS:
      Twelve obstructions with a mean length of 1.4 cm (range 0.4-1.9 cm) were managed.
      The technical success rate was 100%. No major complications occurred, and normal
      renal function was restored. The mean follow-up was 12 months. In 60% of the
      patients, a patent ureter was depicted at 1 week, whereas in four patients,
      repeat dilation of the obstructed segment was required. The stents were removed
      after a mean period of 4.8 weeks. CONCLUSION: Percutaneous nephrostomy and
      primary antegrade ureteral balloon dilation is safe and efficacious for treating
      ureteral injury after pelvic surgery and obviates open surgical manipulations.

PMID- 17206904
TI  - BCG for upper-tract transitional-cell carcinoma: is it safe in patients with
      renal compromise?
AB  - We report three cases of end-stage renal failure necessitating hemodialysis
      subsequent to BCG administration for the treatment of upper-urinary tract
      transitional-cell carcinoma in patients with a solitary kidney, one with normal
      renal function and two with chronic renal failure prior to BCG instillation. We
      discuss treatment-related issues with pertinent literature review.

PMID- 17206905
TI  - Laparoscopic partial cystectomy in the management of bladder endometriosis:
      report of two cases.
AB  - Endometriosis is the proliferation of endometrial tissue outside the normal
      confines of the myometrium or uterine cavity. Endometriosis involving the urinary
      tract occurs in approximately 1% to 2% of cases. The bladder is affected in 80%
      of these patients. The diagnosis of vesical endometriosis is difficult, and it
      should be confirmed by cystoscopy with biopsy. Laparoscopic examination
      represents the gold standard for the diagnosis of pelvic endometriosis. Urinary
      bladder endometriosis may be treated surgically or medically with hormone
      suppressive therapy. However, medical treatments usually are only palliative, and
      symptoms generally recur on discontinuation. We report our experience in two
      patients with vesical endometriosis who were managed successfully with cystoscopy
      assisted laparoscopic partial cystectomy.

PMID- 17206906
TI  - Treatment characteristics and inherent prostatic features do not predict patient
      outcome after high-energy transurethral thermotherapy: a prospective study of
      prostalund feedback treatment.
AB  - PURPOSE: To determine whether treatment characteristics, intrinsic prostatic
      factors, and clinical parameters predict the outcome in patients treated with
      high-energy transurethral microwave thermotherapy (HE-TUMT). PATIENTS AND
      METHODS: A series of 48 consecutive patients, 28 with an indwelling catheter,
      underwent ProstaLund Feedback Treatment (PLFT). The 12-month International
      Prostate Symptom Score response rate (IPSS < or = 7 or > or =50% improvement),
      peak flow rate response rate (Q(max) > or = 15 mL/sec or > or =50% improvement),
      and bladder outflow obstruction index response rate (BOOI <40) were correlated
      with treatment characteristics such as duration, average intraprostatic
      temperature, time with therapeutic intraprostatic temperatures (>45 degrees C),
      average intraprostatic blood flow, consumed energy, and recorded prostate mass
      destruction. Baseline parameters such as age, serum prostate specific antigen
      concentration, prostate volume, and pretreatment IPSS, quality of life (QOL),
      Q(max), postvoiding residual urine volume (PVR), and BOOI were included in the
      logistic regression analysis. RESULTS: Treatment characteristics did not
      discriminate responders and nonresponders to HE-TUMT. For the patients without a
      catheter, the IPSS response (75%) was predicted by higher pretreatment IPSS (P =
      0.041; relative risk [RR] = 3.4) and higher pretreatment PVR (P = 0.026; RR =
      1.1). The Q(max) response (85%) was predicted by higher grades of pretreatment
      obstruction (P = 0.009; RR = 1.02). The BOOI response (60%) was not related to
      any of the factors tested. For the patients with a catheter, no outcome
      predictors could be identified. CONCLUSIONS: According to our results, the
      intraprostatic temperature, the duration of intraprostatic temperatures in the
      therapeutic range, and the pattern of blood flow did not predict HE-TUMT outcome.
      Treatment duration, consumed energy, and the magnitude of tissue necrosis did not
      translate into clinical efficacy. Clinical parameters were important predictors
      of outcome in patients not in retention.

PMID- 17206907
TI  - Macroplastique implantation system for female stress urinary incontinence: long
      term follow-up.
AB  - PURPOSE: To evaluate the 60-month outcome of the Macroplastique Implantation
      System (MIS) for the treatment of female stress urinary incontinence (SUI) caused
      by intrinsic sphincter deficiency evaluated by objective and subjective measures,
      including Quality of Life (QoL) impact. PATIENTS AND METHODS: Twenty-one women,
      mean age 47.4 years, with urodynamically diagnosed intrinsic sphincter deficiency
      were enrolled. They were assessed preoperatively by physical examination, QoL
      (King's Health Questionnaire), Stamey grading of incontinence, pad usage, 1-hour
      pad-weight test, and urodynamic testing. Patients underwent periurethral
      injection of MIS under local anesthesia. After 24-month follow-up, six patients
      were discharged from the group, and the remaining 15 patients were reassessed by
      means of objective and subjective parameters at 6, 12, 24, and 60 months after
      last treatment. RESULTS: Patients' QoL improved in all domains throughout the
      study. The overall subjective success rate was 80%. At 60 months, pad usage was
      reduced from a mean of 3.5/day to 0.9/day, and the 1-hour pad weight decreased
      from 53.8 to 5.9 g. Valsalva leak-point pressure testing demonstrated a 73.3%
      rate of cure/improvement. There was no significant statistical difference
      assessed by Stamey grading and objective cure at 6, 12, 24, and 60 months of
      follow-up. The data showed a stable overall outcome from 6 to 60 months.
      CONCLUSION: The MIS produced promising long-term subjective and objective
      outcomes, as well as long-lasting improvements in QoL. It should be considered a
      good option for certain cases of female SUI.

PMID- 17206908
TI  - Transanal endoscopic microsurgery for correction of rectourethral fistulae.
AB  - BACKGROUND: Rectourethral fistula is a rare complication of radical
      prostatectomy. Transanal endoscopic microsurgery (TEM) is a minimally invasive
      technique available for its surgical correction, although currently, TEM is used
      more commonly for excision of adenomas and stage T(1) carcinomas of the rectum.
      PATIENTS AND METHODS: We report two patients with rectourethral fistulae after
      laparoscopic radical prostatectomy in whom TEM was used for closure. The surgical
      procedure included microscopic full-thickness excision of the rectal wall around
      the fistula with a 1-cm margin and endoscopic suturing of the defect in the
      urethral and rectal walls. RESULTS: In one case, the rectourethral fistula was
      closed using TEM. In the other patient, the procedure, performed after failure of
      a graciloplasty, was difficult because of extensive scar tissue, and the fistula
      persisted. CONCLUSIONS: The TEM procedure is a minimally invasive technique that
      may be considered for surgical repair of rectourethral fistulae.

PMID- 17206909
TI  - Rapid communication: renal apoptosis after shockwave application in rabbit model.
AB  - PURPOSE: To identify any apoptotic effect of shockwave lithotripsy (SWL) on renal
      tubular and glomerular cells. MATERIALS AND METHODS: Thirty-five male New Zealand
      White rabbits were divided into five groups of seven rabbits each: I (control),
      II (sham), and III, IV, and GV (treated and sacrificed 1, 7, and 28 days after
      SWL, respectively). Intramuscular anesthetic agent (ketamine HCl; 20 mg/kg) and
      intravenous contrast medium (iohexol 300 mg of I/mL) were administered to animals
      in group II. The left kidneys of animals in groups III, IV, and V were exposed to
      2000 shockwaves at 18 kV after administration of anesthesia and contrast medium.
      The animals were sacrificed on day 1, 7, or 28 after SWL, and the kidneys were
      removed. Apoptotic and proliferative indices of renal tubular and glomerular
      cells were determined by terminal deoxynucleotidyl transferase dUTP nick and
      label (TUNEL) and Ki-67 labeling methods, respectively, counting 1000 cells in
      each preparation. RESULTS: No apoptosis was detected in glomerular cells in any
      group. The mean apoptotic indices of the tubular cells in animals in groups I and
      II were 483.0 +/- 85 and 484.4 +/- 105, respectively with no significant
      difference between the groups. In groups III and IV, the mean apoptotic indices
      were 343.4 +/- 89 and 358.4 +/- 61, respectively. There were no statistically
      significant differences between groups III and IV and the control group.
      Similarly, there were no significant differences in the apoptotic indices in
      groups III and IV. However, the apoptotic index in group V was 821.4 +/- 57,
      significantly higher than in the control group. The proliferative indices of all
      SWL groups were lower than that of the control group. CONCLUSION: Shockwave
      lithotripsy has an apoptotic effect on renal tubular cells that can be detected 4
      weeks after the procedures, but no apoptotic effect on glomerular cells.
      Treatment with SWL also attenuates the proliferation of both tubular and
      glomerular cells.

PMID- 17206910
TI  - Laparoscopic partial nephrectomy with saline-irrigated KTP laser in a porcine
      model.
AB  - PURPOSE: To evaluate the feasibility of using the potassium titanyl phosphate
      (KTP) laser to perform laparoscopic partial nephrectomy in a porcine model, with
      saline irrigation to reduce intraoperative smoke formation. MATERIALS AND
      METHODS: A high-power (80 W) KTP laser was used without hilar occlusion in 14
      laparoscopic partial nephrectomies in four pigs. During laser discharge, the
      cutting plane was irrigated continuously with saline. RESULTS: Thirteen partial
      nephrectomies were completed. Hemostasis was obtained without the need for any
      non-laser techniques. Only minimal smoke was produced, not affecting visibility
      or the progress of surgery. Histologic examination of the resection margin showed
      only minimal tissue destruction. One procedure failed because the laser fiber
      broke and occluded the suction during the operation. The mean partial nephrectomy
      time was 13.14 minutes (range 7-19 minutes) with a mean estimated blood lost of
      28.57 mL (range 5-80 mL). The mean saline irrigation used for each operation was
      2600 mL (range 1500-3400 mL), and the amount of saline drained out was 1700 mL
      (range 900-3200 mL). CONCLUSION: Laparoscopic partial nephrectomy using the 80 W
      KTP laser is feasible and effective in the porcine model. Saline irrigation
      dramatically reduces smoke formation. The technique is deserving of clinical
      studies after the laser-application device and suction irrigation are refined.

PMID- 17206911
TI  - Effect of freeze time during renal cryoablation: a swine model.
AB  - BACKGROUND AND PURPOSE: Cryotherapy provides a minimally invasive treatment for
      small renal tumors via an open, percutaneous, or laparoscopic approach. We sought
      to determine the most appropriate duration of freezing and the number of probes
      necessary to produce cell death without concomitant morbidity. MATERIALS AND
      METHODS: Nine domestic female pigs were divided into three groups of three
      animals each. Each group underwent a single freeze cycle with a commercially
      available cryotherapy device with 3.4-mm probes: group 1 for 5 minutes, group 2
      for 10 minutes, and group 3 for 15 minutes. The right kidney was treated with a
      single probe, the left with a double probe. Animals were permitted to survive for
      an average of 4.8 days (range 4-7 days), after which the kidneys were harvested.
      A single pathologist examined the kidneys for gross and histologic changes.
      Evidence of complications (fistula, bleeding, bowel injury) was documented at the
      time of necropsy. RESULTS: For group 1, the temperature obtained with a single
      probe 5, 10, 15, and 20 mm from the probe was -57 degrees C, 3 degrees C, 25
      degrees C, and 33 degrees C, respectively; for group 2 -85 degrees C, -37 degrees
      C, -2 degrees C, and 25 degrees C; and for group 3 -10 degrees C, -45 degrees C, 
      20 degrees C, and 6 degrees C. For group 1, the temperature obtained with a
      double probe at 5, 10, 15, and 20 mm from each probe was -65 degrees C, 0 degrees
      C, 20 degrees C, and 30 degrees C, respectively; for group 2 -72 degrees C, -25
      degrees C, 5 degrees C, 25 degrees C; and for Group 3 -82 degrees C, -30 degrees
      C, -12 degrees C, 13 degrees C. Complete necrosis was seen 5 mm from the
      cryoprobe within each group, but only in groups 2 and 3 did necrosis extend 10 mm
      or beyond the probes when utilizing either single or double probes. The maximum
      diameter of consistent necrosis was 35 to 40 mm in the animals in group 3 treated
      with a double probe. Bleeding and renal fracture were the two most common
      complications. CONCLUSIONS: A 5-minute freeze appears to be inadequate to cause
      tissue necrosis and is associated with excessive bleeding at the time of the
      procedure, whereas the 15-minute freeze produces consistent necrosis but is
      associated with renal fracture. In this animal model, the 10-minute freeze with
      the single or double probe configuration appears optimal to produce necrosis
      without complications.

PMID- 17206916
TI  - Bioengineering assessment of acupuncture, part 2: monitoring of microcirculation.
AB  - In the second part of the review article, monitoring of microcirculation during
      acupuncture is described. Laser Doppler flowmetry and laser Doppler imaging
      provide easy-to-use, noninvasive, real-time measurements of local tissue blood
      flow. Using these types of biomedical equipment, it is possible to quantify and
      objectify peripheral changes in microcirculation during different methods of
      acupuncture stimulation (manual needle acupuncture and laserneedle acupuncture).

PMID- 17206917
TI  - Bioengineering assessment of acupuncture, part 3: ultrasound.
AB  - Multidirectional transcranial ultrasound monitoring can be used to prove
      quantifiable effects of acupuncture stimulation in the brain. This third part of
      the review article gives a short introduction in monitoring cerebral blood flow
      velocity and summarizes the scientific results in this area of research. New
      constructions from the Medical University of Graz that can be used for evidence
      based computer-controlled acupuncture are described. With these new methods and
      concepts, reproducible effects of needle and laserneedle acupuncture stimulation
      in cerebral blood flow velocity can be objectified for the first time.

PMID- 17206918
TI  - Bioengineering assessment of acupuncture, part 4: functional magnetic resonance
      imaging.
AB  - In the fourth part of this review article, research on the topic of acupuncture
      and functional magnetic resonance imaging is described. Needle as well as
      painless laserneedle stimulation have led to significant changes in different
      areas of the brain. With the help of modern biomedical engineering equipment and
      neuroscience, some of acupuncture's secrets have begun to be revealed. The neuro
      modulating effects require further investigation in a larger population sample.

PMID- 17206919
TI  - Mechanical impact and articular cartilage.
AB  - Mechanical impact forces on articular cartilage can cause substantial damage. Car
      accidents, falls, and sports injuries have a tremendous effect on the U.S. and
      world populations, both in terms of economic and quality of life costs. While the
      effects of impact forces are known to be damaging, tolerance levels of cartilage
      to these forces and the mechanobiologic sequelae are still mostly unknown. Impact
      studies can be difficult to compare to each other due to the complex array of
      mechanical factors that are involved in a single impact. Previous work includes
      mathematical models, acute effects of impact, and in vivo and explant models of
      impact. These experiments have found that articular cartilage has a threshold
      above which impact forces are damaging, though this threshold is likely dependent
      on many factors, both genetic and environmental. This type of damage has been
      shown to vary according to the severity of the impact, from leaving the articular
      cartilage surface intact to fracture of the subchondral bone. Some studies have
      initiated investigations into ways to ameliorate the injurious response to
      impact, which may allow some patients to avoid the ensuing cartilage degeneration
      and osteoarthritis. Much work remains to be performed in understanding the
      genetic and biochemical response to impact. The goal of this research is to
      eventually decrease the incidence of posttraumatic arthritis and possibly even
      delay primary osteoarthritis, which can be achieved by using a robust testing
      design that includes morphological, biomechanical, quantitative biochemical, and
      genetic characterization of a model system for articular cartilage impact. This
      model system can then be used to test treatments to prevent degenerative changes
      in articular cartilage.

PMID- 17206920
TI  - Review of research on prosthetic devices for lower extremity amputation.
AB  - The literature on lower extremity prostheses from 1989 to 2006 has been reviewed
      in this article. New technologies, such as the microprocessor-controlled
      prosthetic knees and energy-storing/return prosthetic feet, are recent advances
      in the prosthetic field. Despite the extensive research to date in the areas of
      socket design and manufacturing, and alignment of prostheses for optimum gait
      analyses, problems persist in the field. Difficulties in obtaining a comfortable
      socket fit, prostheses weight and alignment guidelines, and the ability to
      rapidly manufacture a prosthetic socket that can accommodate the changing sizes
      of the residual limb persist. Furthermore, no prosthetic device can adjust to the
      typical movements of the human gait. These areas provide opportunities for
      further research and development.

PMID- 17206921
TI  - Vascular and cellular targeting for photodynamic therapy.
AB  - Photodynamic therapy (PDT) involves the combination of photosensitizers (PS) with
      light as a treatment, and has been an established medical practice for about 10
      years. Current primary applications of PDT are age-related macular degeneration
      (AMD) and several types of cancer and precancer. Tumor vasculature and parenchyma
      cells are both potential targets of PDT damage. The preference of vascular versus
      cellular targeting is highly dependent upon the relative distribution of
      photosensitizers in each compartment, which is governed by the photosensitizer
      pharmacokinetic properties and can be effectively manipulated by the
      photosensitizer drug administration and light illumination interval (drug-light
      interval) during PDT treatment, or by the modification of photosensitizer
      molecular structure. PDT using shorter PS-light intervals mainly targets tumor
      vasculature by confining photosensitizer localization within blood vessels,
      whereas if the sensitizer has a reasonably long pharmacokinetic lifetime, then
      PDT at longer PS-light intervals can induce more tumor cellular damage, because
      the photosensitizer has then distributed into the tumor cellular compartment.
      This passive targeting mechanism is regulated by the innate photosensitizer
      physicochemical properties. In addition to the passive targeting approach, active
      targeting of various tumor endothelial and cellular markers has been studied
      extensively. The tumor cellular markers that have been explored for active
      photodynamic targeting are mainly tumor surface markers, including growth factor
      receptors, low-density lipoprotein (LDL) receptors, transferrin receptors, folic
      acid receptors, glucose transporters, integrin receptors, and insulin receptors.
      In addition to tumor surface proteins, nuclear receptors are targeted, as well. A
      limited number of studies have been performed to actively target tumor
      endothelial markers (ED-B domain of fibronectin, VEGF receptor-2, and neuropilin
      1). Intracellular targeting is a challenge due to the difficulty in achieving
      sufficient penetration into the target cell, but significant progress has been
      made in this area. In this review, we summarize current studies of vascular and
      cellular targeting of PDT after more than 30 years of intensive efforts.

PMID- 17206922
TI  - A critical comparison of the current view of Ca signaling with the novel concept
      of F-actin-based Ca signaling.
AB  - A detailed comparative survey on the current idea of Ca signaling and the
      alternative concept of F-actin-based Ca signaling is given. The two hypotheses
      differ in one central aspect - the mechanism of Ca storage. The current theory
      rests on the assumption of Ca-accumulating vesicles derived from the endoplasmic/
      sarcoplasmic reticulum, which are equipped with an ATP-dependent Ca pump and IP3-
      or ryanodine-sensitive Ca-release channels/receptors. The alternative hypothesis
      proceeds from the idea of Ca storage at the high-affinity binding sites of F
      actin subunits. Several prominent features of Ca signaling, which are not
      adequately described by the current concept, are inherent properties of the F
      actin system and its dynamic state of treadmilling. F-actin is the only known
      biological Ca-binding system that has been proven by in vitro experiments to work
      within the physiological range of Ca concentrations and the only system that
      meets all necessary conditions to function as receptor-operated Ca store and as a
      coupling device between the Ca store and the store-operated Ca influx pathway.
      The most important properties of Ca signaling, such as store-channel coupling,
      quantal Ca release, spiking and oscillations, biphasic and "phasic" uptake
      kinetics, and Ca-induced Ca release, turn out to be systematic features of the
      new concept but remain unexplained by the classical vesicle storage hypothesis. A
      number of novel findings, specifically recent reports about direct effects of
      actin-specific toxins on Ca stores, have strengthened the new concept. The
      concept of F-actin-based Ca signaling combined with the notion of microvillar
      regulation of ion and substrate fluxes opens new aspects and far-reaching
      consequences, not only for cellular Ca signaling but also for various other cell
      functions, and represents an opportunity to connect several fields of cell
      physiology on the basis of a common mechanism.

PMID- 17206924
TI  - Oral controlled-release formulation in veterinary medicine.
AB  - The development of controlled-release dosage forms (CRDFs) is highly desirable
      both from a convenience and compliance perspective. Furthermore, these
      formulations release drugs at a prescribed rate, leading to relatively constant
      blood drug concentrations or to pulse dosing. Another benefit is the ability to
      administer medications in infrequent regimens. For example, antimicrobial agents
      generally require very frequent administration regimens. In recent years, the
      pharmaceutical industry has realized the potential of this treatment modality and
      efforts have been made to develop a variety of CRDFs exclusively for veterinary
      use. While there are a number of controlled-release products available for
      veterinary applications, only a limited number of therapeutic niches (such as the
      application of antiparasitic drugs in cattle) are associated with products that
      have been developed as oral controlled-release products. In addition to reviewing
      potential new therapeutic areas where oral controlled-release products can be
      applied in veterinary medicine, this article reviews differences in the
      gastrointestinal tracts of various species and the significance of the
      dissimilarity in the development of CRDFs. Technological aspects involved in
      veterinary CRDFs are also assessed.

PMID- 17206925
TI  - Microneedles and other physical methods for overcoming the stratum corneum
      barrier for cutaneous gene therapy.
AB  - The outermost layer of skin, the epidermis, has developed formidable physical and
      immunological barrier properties that prevent infiltration of deleterious
      chemicals and pathogens. Consequently, transdermal delivery of medicaments is
      currently restricted to a limited number of low molecular weight drugs. As a
      corollary, there has been significant recent interest in providing strategies
      that disrupt or circumvent the principal physical barrier, the stratum corneum,
      for the efficient cutaneous delivery of macromolecular and nucleic acid based
      therapeutics. These strategies include: electrical methods, intradermal
      injection, follicular delivery, particle acceleration, laser ablation,
      radiofrequency ablation, microscission, and microneedles. The application of
      microfabricated microneedle arrays to skin creates transient pathways to enable
      transcutaneous delivery of drugs and macromolecules. Microneedle use is simple,
      pain-free, and causes no bleeding, with further advantages of convenient
      manufacture, distribution, and disposal. To date, microneedles have been shown to
      deliver drug, peptide, antigen, and DNA efficiently through skin. Robust and
      efficient microneedle designs and compositions can be inserted into the skin
      without fracture. Further progress in microneedle array design, microneedle
      application apparatus, and integrated formulation will confirm this methodology
      as a realistic clinical strategy for delivering a range of medicaments, including
      DNA, to and through skin.

PMID- 17206926
TI  - Establishing improved normal values for nerve conduction studies.
AB  - Nerve conduction studies are commonly performed to diagnose injuries of the
      peripheral nerves. In the past, normal ranges have been derived on relatively
      small samples of normal subjects. These ranges were often suboptimal for clinical
      use. Therefore, this series of articles was created to establish an improved
      database of normative values. It highlights the key contributions of a number of
      authors. In this foreword, the contributions of the various authors to the
      special issue on the development of an improved database for nerve conduction
      studies are described. The authors are introduced, including their training,
      gifts, and which articles they were involved in writing. In addition, there is a
      brief review of each of the articles in this special supplement. The fundamentals
      of ulnar motor nerve conduction to the first dorsal interosseous muscle are
      described, as is the contribution of Nate Prahlow, MD. In addition, the median
      motor nerve conduction to the pronator teres muscle and flexor carpi radialis
      muscle is highlighted including the contributions of Brian Foley, MD. The radial
      sensory nerve and dorsal ulnar cutaneous sensory nerve studies are described, as
      well as the contributions of Van Evanoff, Jr., MD, in creating this research.
      Median motor conduction to the lumbrical muscles and ulnar motor conduction to
      the palmar interosseous muscles are described, again highlighting the
      contributions of Dr. Foley. In addition, medial and lateral antebrachial
      cutaneous nerve studies are described, along with the contributions of Dr. Nathan
      Prahlow. Median and ulnar sensory conduction studies recording from the fourth
      digit, as well as median and radial sensory conduction to the first digit, are
      described, as are the contributions of James Lohman, MD, and Andrew Berkson, DO.
      The side-to-side differences in median and ulnar sensory conduction studies and
      the importance of performing such studies are described, as are the contributions
      in this research of Dr. Nathan Prahlow and Elizabeth Grossart, MD. Lastly, median
      and ulnar sensory amplitude differences are described, including the
      contributions of Dr. Zaliha Omar, Dr. Andrew Berkson, and Doug Mottley, MD.

PMID- 17206927
TI  - Ulnar nerve motor conduction to the first dorsal interosseous muscle.
AB  - The ulnar motor study to the abductor digiti minimi (ADM) is commonly performed,
      but does not test the terminal deep palmar branch of the ulnar nerve. Although
      damage to the ulnar nerve most often occurs at the elbow, the damage may occur
      elsewhere along the course of the nerve, including damage to the deep palmar
      branch. Ulnar conduction studies of the deep branch have been performed with
      recording from the first dorsal interosseous (FDI) muscle. These studies have
      used differing methodologies and were mostly limited by small sample size. The
      aim of this study was to develop a normative database for ulnar nerve conduction
      to the FDI. A new method of recording from the FDI was developed for this study.
      It utilizes recording with the active electrode over the dorsal first web space,
      with the reference electrode placed at the fifth metacarpophalangeal joint. This
      technique reliably yields negative takeoff measurements. An additional comparison
      was made between ulnar motor latency with recording at the ADM and with recording
      at the FDI. For this study, 199 subjects with no risk factors for neuropathy were
      tested. The latency, amplitude, area, and duration were recorded. The upper limit
      of normal (ULN) was defined as the 97th percentile of observed values. The lower
      limit of normal (LLN) was defined as the 3rd percentile of observed values. For
      the FDI, mean latency was 3.8 +/- 0.5 ms, with a ULN of 4.7 ms for males, 4.4 ms
      for females, and 4.6 ms for all subjects. Mean amplitude was 15.8 +/- 4.9 mV,
      with a LLN of 5.1 for all subjects. Side-to-side differences in latency to the
      FDI, from dominant to nondominant hands, was -0.1 +/- 0.4 ms, with a ULN of 0.8
      ms. For the amplitude, up to a 52% decrease from side to side was normal. For the
      same-limb comparison of the FDI and ADM, the mean latency difference was 0.6 +/-
      0.4 ms, with a ULN increase of 1.3 ms for latency to the ADM versus the FDI.

PMID- 17206928
TI  - Establishing normal values of the proximal median motor nerve-a study of the
      pronator teres and flexor carpi radialis in healthy volunteers.
AB  - The importance of normative peripheral nerve data is increasing due to advances
      in medical implantation, microsurgical suturing, and tubulization repair
      techniques. Because the median nerve is often affected, its normal values must be
      reliable. Although the distal portion of the median nerve has been well studied
      using electrodiagnostic methods, the proximal forearm segment has not. This study
      establishes a normative database for median nerve conduction to the pronator
      teres (PT) and to the flexor carpi radialis (FCR). Two hundred-eight asymptomatic
      subjects were studied using proximal median motor stimulation at 10 cm.
      Latencies, amplitudes, areas, and durations were recorded. To the pronator teres:
      The upper limit for normal (ULN) motor latency was 3.5 ms (2.9 +/- 0.3 ms). The
      side-to-side latency difference was </= 0.5 ms. Overall, the lower limit of
      normal (LLN) amplitude was 2.2 mV. However, this decreased to 1.5 mV in the over
      50 age group. To the flexor carpi radialis: The ULN motor latency was 3.6 ms (2.8
      +/- 0.4 ms). The side-to-side latency difference was </= 0.7 ms. Overall, the LLN
      amplitude was 2.3 mV. However, this decreased to 1.7 mV in the over-50 group.
      This study produced a large database of normal results for the median motor nerve
      conduction to the pronator teres and to the flexor carpi radialis. The 10-cm
      techniques are easily reproducible and helpful when evaluating this portion of
      the median nerve.

PMID- 17206929
TI  - Radial versus dorsal ulnar cutaneous sensory studies.
AB  - Peripheral nerves injuries are unfortunately common. Neuropathy may result from
      trauma, entrapment, metabolic or hereditary disturbances, inflammatory processes,
      iatrogenic injury from medical implants, and several other causes. We set out to
      create a large normative database for radial and dorsal ulnar cutaneous (DUC)
      sensory studies. Because comparison between two nerves of the same limb can be
      useful in detecting pathology, we also compared the latencies between the two
      nerves. Data were collected on both nerves using a 10-cm antidromic technique
      while controlling for temperature. Included subjects were asymptomatic: radial
      sensory studies were performed on 212 volunteers, DUC sensory studies were
      performed on 194 volunteers, and both studies were performed on 159 volunteers.
      Data were collected for onset and peak latencies, onset-to-peak and peak-to-peak
      amplitudes, area, rise time, and duration. Side-to-side differences were
      investigated. The data were analyzed to determine whether age, race, gender,
      height, weight, or body mass index (BMI) (kg/m2) correlated with different
      results. Differences in latencies between the nerves were analyzed as were side
      to-side differences. Mean values for radial and DUC nerves, respectively, were
      found to be as follows: onset latency 1.9 +/- 0.2 ms and 1.8 +/- 0.3 ms, peak
      latency 2.4 +/- 0.2 ms and 2.3 +/- 0.4 ms, onset-to-peak amplitude 29 +/- 13 muV
      and 17 +/- 10 muV, peak-to-peak amplitude 33 +/- 14 muV and 20 +/- 13 muV, and
      area 18 +/- 7 nVs and 11 +/- 7 nVs. Mean rise time (0.5 +/- 0.1 ms) and duration
      (1.2 +/- 0.2 ms) were identical for both nerves. The upper limit of normal (ULN)
      side-to-side difference in peak latency was 0.3 ms for the radial and 0.4 ms for
      the DUC study. The ULN drop in peak-to-peak amplitude from one side to the other
      was 54% for the radial and 67% for the ulnar study. Increasing age, male gender,
      and increasing BMI (radial only) were associated with lower amplitudes and area,
      though the effects were clinically insignificant. The ULN increase in both radial
      versus-DUC and DUC-versus-radial peak latency was 0.4 ms. In conclusion, a large
      normative database for the radial and DUC sensory studies has been derived that
      will assist in the diagnosis of peripheral neuropathy from a variety of
      etiologies. Side-to-side and internerve comparisons were also made.

PMID- 17206930
TI  - Establishing normal nerve conduction values- lumbrical and interosseous
      responses.
AB  - OBJECTIVE: The importance of normative peripheral nerve data is increasing due to
      the advances in medical implantation, microsurgical suturing, and tubulization
      repair techniques. Because the median and ulnar nerves are often affected, their
      normal values must be reliable. The objective of this study was to create a
      larger database of normative values for the first and second lumbrical responses.
      The differences between the second lumbrical response and the interosseous
      response were also studied. BACKGROUND: The available literature is lacking in
      sample size and rigor, preventing reliable interpretations of normal values.
      METHODS: One hundred ninety-six asymptomatic subjects without risk factors for
      neuropathy were recruited and tested. Stimulations were performed with recording
      at the first lumbrical, second lumbrical, and interosseous muscles. RESULTS: Mean
      latency to the first lumbrical was 3.6 +/- 0.4 ms. Mean amplitude was 2.5 +/- 2.0
      mV. The mean difference between latencies to the first lumbrical and second
      lumbrical was 0.1 +/- 0.3 ms, with the second lumbrical usually being the larger
      value. The mean difference between latencies to the abductor pollicic brevis
      (APB) and the first lumbrical was 0.2 +/- 0.4 ms, with the APB latency usually
      being the larger value. Mean latency to the second lumbrical was 3.7 +/- 0.4 ms
      and to the interosseous was 3.1 +/- 0.3 ms. Mean amplitude to the second
      lumbrical was 3.0 +/- 2.0 mV and to the interosseous was 6.9 +/- 2.3 mV. The mean
      difference between latencies to the second lumbrical and interosseous was 0.4 +/-
      0.4 ms, with the second lumbrical usually being the larger value. The upper limit
      of normal increase of latency of the second lumbrical over the interosseous was
      1.2 ms. The upper limit of normal increase of latency in subjects for which the
      interosseous latency exceeded the second lumbrical was 0.2 ms. CONCLUSIONS: This
      study provides a large normative database for nerve conduction studies to the
      first and second lumbricals, as well as to the second interosseous muscle.

PMID- 17206931
TI  - An antidromic study of the medial antebrachial cutaneous nerve, with a comparison
      of the differences between medial and lateral antebrachial cutaneous nerve
      latencies.
AB  - Electrodiagnostic study of the medial antebrachial cutaneous (MAC) and lateral
      antebrachial cutaneous (LAC) nerves is not routinely undertaken. Pathology of
      either nerve or of the brachial plexus may occur from a variety of causes.
      Iatrogenic injury of these nerves has been rarely reported, but potential exists
      for nerve damage with a number of medical procedures, implants, or surgeries in
      the flexor forearm. In any of these situations, nerve conduction studies on the
      MAC and the LAC can be of benefit. Previous studies have reported normal values
      and examined side- to-side differences in the LAC, but have not compared the
      latencies of the MAC to the LAC in the same limb. This study establishes normal
      nerve conduction study values for the MAC from 207 subjects with no risk factors
      for neuropathy, using a 10-cm distance and an antidromic technique. It also
      examines both side-to-side differences in the MAC and same-limb differences
      between the MAC and LAC. For this study, the upper limit of normal (ULN) was
      defined as the 97th percentile of observed values. The lower limit of normal
      (LLN) was defined as the 3rd percentile of observed values. The onset latency,
      peak latency, onset-to-peak amplitude, peak-to-peak amplitude, rise time, and
      duration were recorded. For the MAC, the mean onset latency was 1.7 +/- 0.2 ms,
      with a ULN of 2.0 ms. Mean peak latency was 2.2 +/- 0.2 ms, with a ULN of 2.6 ms.
      Onset-to-peak amplitude was 13 +/- 7 muV, with a LLN of 4 muV. Peak-to-peak
      amplitude was 10 +/- 7 muV, with a LLN of 3 muV. Side-to-side differences in MAC
      onset and peak latencies were 0.0 +/- 0.2 ms, with a ULN of 0.3 ms. Up to a 67%
      side-to-side decrease in MAC onset-to-peak amplitude was within the normal range.
      A 78% side- to-side decrease in MAC peak-to-peak amplitude was within the normal
      range. For the same-limb comparison of the MAC and the LAC, both onset and peak
      latencies had a mean difference of 0.0 +/- 0.2 ms and a ULN of 0.3 ms, regardless
      of whether the MAC or the LAC had the longer latency.

PMID- 17206932
TI  - Median and ulnar antidromic sensory studies to the fourth digit.
AB  - The literature documents multiple reports of neurological injury resulting from
      both the implantation and the removal of orthopedic devices. These injuries can
      be easily and objectively evaluated with nerve conduction studies. This study was
      undertaken to derive a normative database for median and ulnar sensory conduction
      studies to the fourth digit. Testing was done utilizing a 14-cm antidromic
      technique on 192 asymptomatic subjects with no risk factors for neuropathy. The
      subjects were studied bilaterally. Onset latency, peak latency, onset-to-peak
      amplitude, peak-to-peak amplitude, rise time, and duration were recorded.
      Increasing age and body mass index were associated with decreasing amplitudes and
      area. No other demographic factors correlated with differences in waveform
      measurements. Mean onset latency was 2.7 +/- 0.3 ms for the median nerve and 2.6
      +/- 0.2 for the ulnar nerve. Mean peak latency was 3.4 +/- 0.3 ms for the median
      nerve and 3.3 +/- 0.3 ms for the ulnar nerve. Mean onset-to-peak amplitude was 21
      +/- 12 muV for the median nerve and 23 +/- 12muV for the ulnar nerve. Mean peak
      to-peak amplitude was 34 +/- 20 muV for the median nerve and 36 +/- 23 muV for
      the ulnar nerve. Mean area was 25 +/- 17 nVs for the median nerve and 28 +/- 19
      nVs for the ulnar nerve. Mean rise time was 0.7 +/- 0.1 ms for the median nerve
      and 0.7 +/- 0.2 ms for the ulnar nerve. Mean duration was 1.9 +/- 0.4 ms for the
      median nerve and 1.9 +/- 0.5 ms for the ulnar nerve. The mean difference in onset
      and peak latency between the median and ulnar nerves (median minus ulnar) was 0.1
      +/- 0.2 ms. The upper limit of normal difference of median greater than ulnar
      onset and peak latency was 0.5 ms. The upper limit of normal difference of ulnar
      greater than median onset latency was 0.2 ms (0.3 ms for peak latency). The upper
      limit of normal drop in median peak-to-peak amplitude from one side to the other
      was 56%. For the ulnar nerve this value was 73%.

PMID- 17206933
TI  - Comparison of median and radial sensory studies to the thumb.
AB  - There are multiple reports of neurological injury from both the implantation and
      the removal of devices utilized in orthopedics. Nerve conduction studies can be a
      valuable tool in evaluating the acuity, severity, and prognosis of these
      injuries, as well as in tracking their course. This study was undertaken in an
      effort to create a large normative database for examining median and radial
      sensory nerve conduction studies to the first digit. An antidromic technique was
      employed utilizing a 10-cm distance between the stimulating and recording
      electrodes. Two hundred three asymptomatic volunteers were tested. Onset latency,
      peak latency, onset-to-peak amplitude, peak-to-peak amplitude, area, rise time,
      and duration of the waveforms were measured. Males, older subjects, and those
      with higher body mass index (BMI) were found to have lower amplitude and area on
      the median nerve studies. Age was the only variable which demonstrated
      significant correlation with differing results on the radial nerve studies. Mean
      onset latencies were 2.1 +/- 0.2 ms for the median nerve and 2.0 +/- 0.2 ms for
      the radial nerve. Mean peak latencies were 2.7 +/- 0.2 ms for the median nerve
      and 2.6 +/- 0.2 ms for the radial nerve. Mean peak-to-peak amplitude for the
      median nerve was 45 +/- 24 muV and for the radial nerve was 12 +/- 9 muV. The
      upper limit of normal difference in median-versus-radial onset latency was 0.5 ms
      (0.6 ms for peak latency). The upper limit of normal difference in radial-minus
      median onset latency was 0.3 ms (0.4 ms for peak latency).

PMID- 17206934
TI  - Acceptable differences in sensory and motor latencies between the median and
      ulnar nerves.
AB  - The median and ulnar nerves are often studied during the same electrodiagnostic
      examination. The sensory and motor latencies of these nerves have been compared
      to detect a common electrodiagnostic entity: median neuropathy at the wrist.
      However, this comparison could also be used to diagnose less common ulnar
      pathology. For this reason, it is important to establish normal values for
      comparing median and ulnar sensory and motor latencies. Previous research
      deriving these differences in latency has had some limitations. The purpose of
      this study was to derive an improved normative database for the acceptable
      differences in latency between the median and ulnar sensory and motor nerves of
      the same limb. Median and ulnar sensory and motor latencies were obtained from
      219 and 238 asymptomatic risk-factor-free subjects, respectively. An analysis of
      variance was performed to determine whether physical characteristics,
      specifically age, race, gender, height, or body mass index (as an indicator of
      obesity), correlated with differences in latency. Differences in sensory
      latencies were unaffected by physical characteristics. The upper limit of normal
      difference between median and ulnar (median longer than ulnar) onset latency was
      0.5 ms (97th percentile), whereas the peak latency value was 0.4 ms (97th
      percentile). The upper limit of normal difference between ulnar-versus-median
      (ulnar longer than median) onset latency was 0.3 ms (97th percentile), whereas
      the peak-latency value was 0.5 ms (97th percentile). The mean difference in motor
      latencies correlated with age, with older subjects having a greater variability.
      In subjects aged 50 and over, the mean difference in median-versus-ulnar latency
      was 0.9 ms +/- 0.4 ms. The upper limit of normal difference (median longer than
      ulnar) was 1.7 ms (97th percentile). The upper limit of normal ulnar motor
      latency is attained if the ulnar latency comes within 0.3 ms of the median
      latency. In individuals less than 50 years of age, the mean difference in latency
      was 0.6 ms +/- 0.4 ms, with the median latency usually being greater than the
      ulnar. The upper limit of normal difference (median longer than ulnar) was 1.4 ms
      (97th percentile), whereas the upper limit of ulnar latency relative to median
      latency was attained if the ulnar latency was equal to median latency.

PMID- 17206935
TI  - Median and Ulnar 14-cm Antidromic Sensory Studies to the Third and Fifth Digits-A
      Comparison of Amplitude.
AB  - There are multiple reports of peripheral nerve injury following the implantation
      or removal of surgical hardware. Electrodiagnostic testing can be useful in
      assessing the chronicity, severity, and recovery of such a nerve injury. The
      purpose of this study is to establish a normative data set to allow for
      comparison of median and ulnar antidromic sensory peak-to-peak amplitude values.
      Median and ulnar antidromic sensory studies to digits 3 and 5 are commonly
      performed in electrodiagnosis to aid in the diagnosis of a variety of clinical
      conditions. Numerous studies have examined normal latency and amplitude values
      for these studies. To our knowledge there has been one other study that compared
      the relationship between median and ulnar sensory amplitude results taken from
      the same limb. That study had limited generalizability to the population at
      large. One hundred-nineteen volunteers were tested with antidromic sensory
      technique to digits 3 and 5 at 14-cm stimulation distance. Peak latency and peak
      to-peak amplitude were recorded. Possible relationships between age, gender,
      height, weight, BMI, and median and ulnar amplitude were examined through simple
      linear regressions. Age, weight, height, and BMI were all found to negatively
      correlate with both median and ulnar amplitude. Female subjects were found to
      have statistically greater median and ulnar amplitudes than male subjects.
      Factors were said to be statistically significant at the P </= 0.05 level. The
      mean median peak latency was 3.2 +/- 0.3 ms. The mean ulnar peak latency was 3.2
      +/- 0.4 ms. The mean median peak-to-peak amplitude was 87 +/- 36 muV. The mean
      ulnar peak-to-peak amplitude was 72 +/- 34 muV. The upper limit of normal
      difference (2.5th percentile) in median-versus-ulnar amplitude was a 56% drop
      from median-to-ulnar amplitude, or a 59% drop from ulnar-to-median amplitude.
      This allows for amplitude comparisons to be made between these two nerves.

PMID- 17206936
TI  - Urocortin 1 modulates the neurohumoral response to acute nitroprusside-induced
      hypotension in sheep.
AB  - In addition to haemodynamic actions, Ucn1 (urocortin 1) has been reported to
      affect a number of hormonal systems; however, it remains unclear whether Ucn1
      modulates circulating hormones under physiological conditions. Accordingly, in
      the present study, we have examined the effects of Ucn1 on haemodynamics,
      hormones and renal indices in normal conscious sheep subjected to a nitroprusside
      induced hypotensive stimulus designed to alter hormonal levels within the
      physiological range. Ucn1 administration did not alter the haemodynamic response
      to nitroprusside-induced hypotension. However, compared with the rise observed on
      the control day, plasma ANP (atrial natriuretic peptide; P=0.043), BNP (brain
      natriuretic peptide; P=0.038) and endothelin-1 (P=0.011) levels were reduced
      following Ucn1 administration. Associated with this significant reduction in
      natriuretic peptides, the increase in urinary sodium output associated with
      rising pressures post-nitroprusside was abolished following Ucn1 administration
      (P=0.048). Ucn1 had no significant effect on the response of hormones of the
      renin-angiotensin-aldosterone system or the hypothalamo-pituitary-adrenal axis.
      In conclusion, Ucn1, administered at physiologically relevant levels during
      nitroprusside-induced hypotension, attenuates the secretion/release of endothelin
      1 and the cardiac natriuretic peptides ANP and BNP. Suppression of ANP and BNP
      probably led to an attenuated natriuretic response to recovery from acute
      hypotension. The threshold for the action of Ucn1 on the natriuretic peptides and
      endothelin-1 appears to be below that of other actions of Ucn1.

PMID- 17206937
TI  - Pathway of biogenesis of apolipoprotein E-containing HDL in vivo with the
      participation of ABCA1 and LCAT.
AB  - We have investigated the ability of apoE (apolipoprotein E) to participate in the
      biogenesis of HDL (high-density lipoprotein) particles in vivo using adenovirus
      mediated gene transfer in apoA-I-/- (apolipoprotein A-I) or ABCA1-/- (ATP-binding
      cassette A1) mice. Infection of apoA-I-/- mice with 2x10(9) pfu (plaque-forming
      units) of an apoE4-expressing adenovirus increased both HDL and the
      triacylglycerol-rich VLDL (very-low-density lipoprotein)/IDL (intermediate
      density lipoprotein)/LDL (low-density lipoprotein) fraction and generated
      discoidal HDL particles. ABCA1-/- mice treated similarly failed to form HDL
      particles, suggesting that ABCA1 is essential for the generation of apoE
      containing HDL. Combined infection of apoA-I-/- mice with a mixture of
      adenoviruses expressing both apoE4 (2x10(9) pfu) and human LCAT
      (lecithin:cholesterol acyltransferase) (5x10(8) pfu) cleared the triacylglycerol
      rich lipoproteins, increased HDL and converted the discoidal HDL into spherical
      HDL. Similarly, co-infection of apoE-/- mice with apoE4 and human LCAT corrected
      the hypercholesterolaemia and generated spherical particles, suggesting that LCAT
      is essential for the maturation of apoE-containing HDL. Overall, the findings
      indicate that apoE has a dual functionality. In addition to its documented
      functions in the clearance of triacylglycerol-rich lipoproteins, it participates
      in the biogenesis of HDL-sized apoE-containing particles. HDL particles generated
      by this pathway may account at least for some of the atheroprotective functions
      of apoE.

PMID- 17206938
TI  - Reggie/flotillin proteins are organized into stable tetramers in membrane
      microdomains.
AB  - Reggie-1 and -2 proteins (flotillin-2 and -1 respectively) form their own type of
      non-caveolar membrane microdomains, which are involved in important cellular
      processes such as T-cell activation, phagocytosis and signalling mediated by the
      cellular prion protein and insulin; this is consistent with the notion that
      reggie microdomains promote protein assemblies and signalling. While it is
      generally known that membrane microdomains contain large multiprotein assemblies,
      the exact organization of reggie microdomains remains elusive. Using chemical
      cross-linking approaches, we have demonstrated that reggie complexes are composed
      of homo- and hetero-tetramers of reggie-1 and -2. Moreover, native reggie
      oligomers are indeed quite stable, since non-cross-linked tetramers are resistant
      to 8 M urea treatment. We also show that oligomerization requires the C-terminal
      but not the N-terminal halves of reggie-1 and -2. Using deletion constructs, we
      analysed the functional relevance of the three predicted coiled-coil stretches
      present in the C-terminus of reggie-1. We confirmed experimentally that reggie-1
      tetramerization is dependent on the presence of coiled-coil 2 and, partially, of
      coiled-coil 1. Furthermore, since depletion of reggie-1 by siRNA (small
      interfering RNA) silencing induces proteasomal degradation of reggie-2, we
      conclude that the protein stability of reggie-2 depends on the presence of reggie
      1. Our data indicate that the basic structural units of reggie microdomains are
      reggie homo- and hetero-tetramers, which are dependent on the presence of reggie
      1.

PMID- 17206939
TI  - SUMF1 enhances sulfatase activities in vivo in five sulfatase deficiencies.
AB  - Sulfatases are enzymes that hydrolyse a diverse range of sulfate esters.
      Deficiency of lysosomal sulfatases leads to human diseases characterized by the
      accumulation of either GAGs (glycosaminoglycans) or sulfolipids. The catalytic
      activity of sulfatases resides in a unique formylglycine residue in their active
      site generated by the post-translational modification of a highly conserved
      cysteine residue. This modification is performed by SUMF1 (sulfatase-modifying
      factor 1), which is an essential factor for sulfatase activities. Mutations in
      the SUMF1 gene cause MSD (multiple sulfatase deficiency), an autosomal recessive
      disease in which the activities of all sulfatases are profoundly reduced. In
      previous studies, we have shown that SUMF1 has an enhancing effect on sulfatase
      activity when co-expressed with sulfatase genes in COS-7 cells. In the present
      study, we demonstrate that SUMF1 displays an enhancing effect on sulfatases
      activity when co-delivered with a sulfatase cDNA via AAV (adeno-associated virus)
      and LV (lentivirus) vectors in cells from individuals affected by five different
      diseases owing to sulfatase deficiencies or from murine models of the same
      diseases [i.e. MLD (metachromatic leukodystrophy), CDPX (X-linked dominant
      chondrodysplasia punctata) and MPS (mucopolysaccharidosis) II, IIIA and VI]. The
      SUMF1-enhancing effect on sulfatase activity resulted in an improved clearance of
      the intracellular GAG or sulfolipid accumulation. Moreover, we demonstrate that
      the SUMF1-enhancing effect is also present in vivo after AAV-mediated delivery of
      the sulfamidase gene to the muscle of MPSIIIA mice, resulting in a more efficient
      rescue of the phenotype. These results indicate that co-delivery of SUMF1 may
      enhance the efficacy of gene therapy in several sulfatase deficiencies.

PMID- 17206940
TI  - Systematic review: managing anaemia in Crohn's disease.
AB  - BACKGROUND: Anaemia is a serious complication of Crohn's disease that triggers
      hospitalization and, if not interfered with, may lead to death. AIMS: To
      systematically summarize and compare the literature on anaemia in Crohn's
      disease. METHODS: For this systematic review the literature was searched for
      English-language articles using anaemia, Crohn* and IBD as key words. 144
      articles were identified and sorted according to the following topics:
      prevalence, aetiology, diagnostic tests and therapy. RESULTS: The reported
      prevalence of anaemia varied between 6.2% and 73.7%, with higher reported
      frequencies in older studies and in in-patients. Iron deficiency is the most
      common underlying condition. Vitamin B12 deficiency is related to the extent of
      ileal resection but has rarely impact on anaemia. Diagnostic criteria are not
      established and treatment guidelines are missing. Oral iron supplementation seems
      effective for short periods but intolerance leads to discontinuation in up to
      21%. Eleven of 11 studies show that oral iron enhances intestinal inflammation
      and colon carcinogenesis in animal models of colitis. Intravenous iron
      supplementation with iron sucrose has been tested in over 250 Crohn's disease
      patients, is safe, effective and does not carry such hazards. CONCLUSIONS: As
      disease activity is determining the degree of anaemia in Crohn's disease,
      implementation of more effective therapy for Crohn's disease will lower its
      incidence. However, further studies regarding the safety and effectiveness of
      iron supplementation are needed.

PMID- 17206941
TI  - Review article: tolevamer, a novel toxin-binding polymer: overview of preclinical
      pharmacology and physicochemical properties.
AB  - BACKGROUND: Tolevamer is a novel toxin-binding polymer that is currently being
      investigated in clinical trials for the treatment of patients who have
      Clostridium difficile-associated diarrhoea. AIMS: To summarize the results of in
      vitro and in vivo preclinical studies of tolevamer. In contrast to antibiotics,
      tolevamer binds C. difficile toxins to interrupt toxin-mediated intestinal
      inflammation and tissue damage, and does not demonstrate direct antimicrobial
      activity. METHODS: Pharmacokinetics/pharmacodynamics were studied in rats and
      dogs; efficacy was studied in a hamster model. RESULTS: Studies in rats and dogs
      indicate that tolevamer is essentially non-absorbed from the gastrointestinal
      tract and show that drug interactions with commonly used therapies are unlikely.
      Pharmacologic studies indicate that tolevamer reduces disease severity and
      recurrence rates in the hamster model of C. difficile-associated diarrhoea and
      blocks the enterotoxic effects of toxin A in rat ileum. The binding parameters
      calculated for the interaction of tolevamer with toxins A and B provide a
      reasonable physicochemical model that supports the potential clinical utility of
      tolevamer. CONCLUSIONS: These preclinical results are consistent with the
      effectiveness and safety profile of tolevamer observed in clinical studies in
      patients with C. difficile-associated diarrhoea.

PMID- 17206942
TI  - Systematic review and meta-analysis: D-Penicillamine vs. placebo/no intervention
      in patients with primary biliary cirrhosis--Cochrane Hepato-Biliary Group.
AB  - BACKGROUND: D-Penicillamine is used for patients with primary biliary cirrhosis
      due to its ability to decrease hepatic copper and modulate the immune response.
      The results on effects of D--penicillamine in randomized-clinical trials of
      primary biliary cirrhosis patients are inconsistent. AIM: To systematically
      evaluate the benefits and harms of D-penicillamine for patients with primary
      biliary cirrhosis. METHODS: We have performed a systematic review with meta
      analyses of randomized-clinical trials to evaluate the effects of D-penicillamine
      for primary biliary cirrhosis. The primary outcomes are mortality and mortality
      or liver transplantation. We analysed the data by fixed-effect and random-effect
      models. RESULTS: Seven randomized trials including 706 patients were analysed. d
      Penicillamine was without significant effects on mortality (RR 1.08, 95% CI: 0.82
      1.43, P = 0.56), mortality or liver transplantation (RR 1.11, 95% CI: 0.74-1.68,
      P = 0.62), pruritus, liver complications, progression of liver histological stage
      and liver biochemical variables. D--Penicillamine significantly decreased serum
      alanine aminotransferase activity (weighted mean difference -45 IU/L, 95% CI: -75
      to -15, P < 0.05) and led to significantly more adverse events (RR 4.18, 95% CI:
      1.38-12.69, P = 0.01). CONCLUSION: D-Penicillamine did not appear to reduce the
      risk of mortality or morbidity, and led to more adverse events in patients with
      primary biliary cirrhosis.

PMID- 17206943
TI  - Pharmacokinetics and bone effects of budesonide in primary biliary cirrhosis.
AB  - BACKGROUND/AIM: To evaluate the safety of budesonide in primary biliary
      cirrhosis. METHODS: 77 primary biliary cirrhosis patients, with stages I-III at
      entry, were randomized to use either budesonide 6 mg and ursodeoxycholic acid 15
      mg/kg (group A), or ursodeoxycholic acid alone (group B) daily for 3 years. In 22
      patients, budesonide pharmacokinetics was determined after 3 years. Bone mass
      density was measured in 62 patients at baseline and 3 years; in 57 patients also
      liver biopsies were performed. RESULTS: At 3 years, no significant differences in
      the pharmacokinetics of budesonide were found between the patients with stages 0
      I, II and III primary biliary cirrhosis. In group A, bone mass density in femoral
      neck and lumbar spine were decreased by 3.6% (P = 0.0002) and 2.8% (P = 0.003)
      from the baseline. In group B, the corresponding decreases were 1.9% (P = 0.029)
      and 0.7% (P = 0.25), but the differences between the groups were not
      statistically significant (P = 0.16 for femoral neck and P = 0.08 for lumbar
      spine). CONCLUSIONS: The plasma concentrations of budesonide do not significantly
      differ within stages I-III primary biliary cirrhosis patients. The combination of
      budesonide and ursodeoxycholic acid may decrease bone mass density in the femoral
      neck and lumbar spine in some primary biliary cirrhosis patients, and bone mass
      density is recommended to be monitored during budesonide therapy.

PMID- 17206944
TI  - Effect of vitamin E on aminotransferase levels and insulin resistance in children
      with non-alcoholic fatty liver disease.
AB  - BACKGROUND: Few data are available on the effect of antioxidants in paediatric
      non-alcoholic fatty liver disease (NAFLD). AIM: To compare the effect of a
      nutritional programme alone or combined with alpha-tocopherol and ascorbic acid
      on alanine aminotransferase (ALT) levels, and insulin resistance (IR) in biopsy
      proven NAFLD children. METHODS: IN a 12-month double-blind placebo study, 90
      patients were prescribed a balanced calorie diet (25-30 cal/kg/d), physical
      exercise, and placebo (group A) or alpha-tocopherol 600 IU/day plus ascorbic acid
      500 mg/day (group B). IR was estimated by the homeostasis model assessment (HOMA
      IR). RESULTS: At month 12, ALT (32.67 +/- 8.09 vs. 32.18 +/- 11.39 IU/L; P = NS),
      HOMA-IR (1.52 +/- 0.66 vs. 1.84 +/- 0.95 IU/L; P = NS), and weight loss (32% vs.
      35% of excessive body weight; P = NS) did not differ between the two arms. Among
      subjects who lost >or=20% of their excessive weight, ALT and body weight
      percentage changes were significantly related (r(o) = 0.260; P = 0.03). In
      subjects, who lost more than 1.0 kg, HOMA-IR significantly decreased (2.20 +/-
      0.21 to 1.57 +/- 0.13 in group A (P <or= 0.01; -8%); 2.91 +/- 0.24 to 1.88 +/-
      0.16 in group B (-32%; P <or= 0.0001)). ALT decreased by 36% (59.13 +/- 4.11 vs.
      30.27 +/- 1.46 IU/L; P <or= 0.001), and 42% (68.19 +/- 5.68 vs. 31.92 +/- 1.92
      IU/L; P <or= 0.0001). In a multivariate analysis, fasting insulin changes in
      group A (P = 0.012; F = 7.150). CONCLUSIONS: Diet and physical exercise in NAFLD
      children seem to lead to a significant improvement of liver function and glucose
      metabolism beyond any antioxidant therapy.

PMID- 17206945
TI  - Antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim
      like/membranous' patterns: diagnostic accuracy for primary biliary cirrhosis.
AB  - BACKGROUND: Serum antinuclear antibodies giving the 'multiple nuclear dots' or
      the 'rim-like/membranous' patterns are frequently detected by indirect
      immunofluorescence on HEp-2 cells in patients with primary biliary cirrhosis.
      AIM: To assess the accuracy of multiple nuclear dot and rim-like/membranous
      antinuclear antibodies for the diagnosis of primary biliary cirrhosis. METHODS:
      Sera from 4371 consecutive patients referred to our laboratory were analysed
      under code for antinuclear antibodies testing by indirect immunofluorescence on
      HEp-2 cells. RESULTS: Review of the clinical records of the 4371 patients allowed
      identification of 101 patients with antimitochondrial antibody-positive primary
      biliary cirrhosis and 22 with antimitochondrial antibody-negative variant.
      Multiple nuclear dot and/or rim-like/membranous patterns were found in 59 (1.3%)
      of the 4371 patients: 31 antimitochondrial antibody-positive primary biliary
      cirrhosis, 17 antimitochondrial antibody-negative primary biliary cirrhosis and
      11 non-primary biliary cirrhosis. The specificity for primary biliary cirrhosis
      of both the antinuclear antibodies pattern was 99%. Positive predictive value and
      likelihood ratio for a positive test were 86% (95% CI: 72.7-94) and 221 (95% CI:
      91.7-544) for multiple nuclear dot, 79% (95% CI: 62.2-90.1) and 132 (95% CI: 56.8
      312.7) for rim-like/membranous, respectively. CONCLUSIONS: Multiple nuclear dot
      and rim-like/membranous antinuclear antibodies are rare findings. Their
      positivity strongly suggests the diagnosis of primary biliary cirrhosis,
      irrespective of antimitochondrial antibody status. The high specificity for
      primary biliary cirrhosis makes them a useful diagnostic tool especially in
      antimitochondrial antibody-negative patients.

PMID- 17206946
TI  - Use of antisecretory drugs among consumers of non-steroidal anti-inflammatory
      drugs in the general population.
AB  - BACKGROUND: Overall success of prophylactic strategies against non-steroidal anti
      inflammatory drug (NSAID) complications depends on the use of gastroprotective
      drugs. AIM: We examined the use of antisecretory drugs in NSAID users in the
      general population of Spain. PARTICIPANTS AND METHODS: In 2002, a phone interview
      was conducted with 2500 persons representative of the general population of
      Spain. Using a validated questionnaire, we asked about the use of NSAID, aspirin
      and antisecretory drugs, and history of digestive diseases. We estimated the use
      of antisecretory drugs in NSAID users, according to risk factors for
      gastrointestinal (GI) lesions associated with NSAID. RESULTS: In total, 425
      persons [17.0% (95% CI 15.5-18.5%)] were NSAID users. Of them, 69 persons (16.2%;
      95% CI 12.7-19.7%) used antisecretory drugs [proton pump inhibitor (PPI) 11.8%
      and H2-blocker 4.9%]. Forty-four of the 224 NSAID users (19.6%) with one risk
      factor for GI lesions were antisecretory drug users (PPI 16%; H2-blocker 4%),
      compared with 24 of the 197 NSAID users (12.7%) without risk factors (PPI 6.6%;
      H2-blocker 6.1%). NSAID users with risk factors for GI lesions but without upper
      GI (UGI) symptoms did not consume more antisecretory drugs than equivalent non
      NSAID users (12.9% vs. 10.7%). CONCLUSION: Current strategies to prevent GI
      lesions in NSAID users are not effective from a population perspective,
      especially in subjects without UGI symptoms.

PMID- 17206947
TI  - Oesophageal mucosal involvement in patients with systemic sclerosis receiving
      proton pump inhibitor therapy.
AB  - AIM: To assess the prevalence of oesophagitis, Barrett's oesophagus (BE) and
      other oesophageal mucosal abnormalities in patients with systemic sclerosis (SSc)
      without prior selection on digestive clinical presentation. We also investigated
      the association between oesophageal endoscopic and manometric data with clinical
      manifestations of SSc. METHODS: Oesophageal endoscopy and manometry were
      performed in 133 consecutive patients with SSc, receiving proton pump inhibitor
      (PPI) therapy since SSc diagnosis. RESULTS: Endoscopy revealed oesophagitis in 43
      patients (32.3%), BE in 9 patients (6.8%), candidiasis in 7 patients (5.3%) and
      hyperplastic polyp arising in ectopic gastric mucosa in 1 patient. Patients with
      severe oesophageal motor impairment further exhibited a higher prevalence of
      interstitial lung disease (ILD) when compared with those without. CONCLUSION: Our
      study underlines the high frequency of oesophageal mucosal abnormalities in
      unselected SSc patients receiving long-term PPI therapy. A relationship between
      oesophagitis/BE and severe manometric motor disturbances was established; these
      patients may require a higher regimen of PPI. Finally, our series indicates a
      correlation between severe oesophageal motor disturbances and evidence for ILD in
      patients, suggesting that gastro-oesophageal reflux may be one of the
      contributing factors of ILD in SSc; this subgroup of patients may require close
      monitoring of lung parameters.

PMID- 17206948
TI  - An in vitro comparison of different providers to deliver four proton pump
      inhibitor products through a feeding tube.
AB  - BACKGROUND: It is unclear how delivery through a feeding tube compares between
      esomeprazole in water, lansoprazole oral disintegrating tablet in water,
      omeprazole/NaHCO(3) in water and simplified lansoprazole suspension. AIM: This in
      vitro study compared delivery through a narrow calibre (8F) feeding tube among
      four proton pump inhibitors when given by skilled [nurse; (n = 8)] or unskilled
      [lay; (n = 8)] providers. METHODS: Following standard instruction, subjects were
      observed delivering each proton pump inhibitor in a sequential, but random,
      fashion to evaluate administration quality and time. Delivery was quantified
      using high-performance liquid chromatography methods and subject preferences were
      evaluated. RESULTS: Delivery (%), similar between lansoprazole oral
      disintegrating tablet (95.7 +/- 3.2) and omeprazole/NaHCO(3) (96.1 +/- 3.0), was
      both greater for lansoprazole oral disintegrating tablet than esomeprazole in
      water (88.9 +/- 8.6; P = 0.006) or simplified lansoprazole suspension (86.1 +/-
      9.5; P = 0.0001) and omeprazole/NaHCO(3) than esomeprazole in water (P = 0.004)
      or simplified lansoprazole suspension (P < 0.001), and was not affected by prior
      subject experience. Quality was higher with both omeprazole/NaHCO(3) and
      lansoprazole oral disintegrating tablet than simplified lansoprazole suspension.
      Administration was quicker for lansoprazole oral disintegrating tablet than
      esomeprazole in water. Subjects preferred lansoprazole oral disintegrating tablet
      and omeprazole/NaHCO(3). CONCLUSIONS: When given through an in vitro feeding
      tube, omeprazole/NaHCO(3) and lansoprazole oral disintegrating tablet lead to
      greater drug delivery, improved administration quality and higher user
      satisfaction, than either esomeprazole in water or simplified lansoprazole
      suspension.

PMID- 17206949
TI  - Does CDX2 expression predict Barrett's metaplasia in oesophageal columnar
      epithelium without goblet cells?
AB  - BACKGROUND: Intestinal metaplasia (Barrett's oesophagus), but not cardiac-type
      mucosa in columnar-lined oesophagus, is regarded as premalignant. As intestinal
      metaplasia and cardiac-type mucosa are endoscopically indiscernible, it is
      difficult to take targeted samples from columnar-lined oesophagus with
      consequently a risk of having undetected intestinal metaplasia. AIM: To
      investigate whether the intestinal markers CDX2, MUC2 and villin can predict the
      presence of undetected intestinal metaplasia in columnar-lined oesophagus.
      Methods Presence of intestinal metaplasia or cardiac-type mucosa was identified
      in 122 biopsy sets of columnar-lined oesophagus from 61 patients, collected at
      two subsequent follow-up upper endoscopies. CDX2, MUC2 and villin expression were
      determined by immunohistochemistry. RESULTS: All intestinal metaplasia samples
      (55) were positive for CDX2 and MUC2 and 32 of 55 for villin. CDX2 expression was
      detected in 23 of 67 (34%) samples with only cardiac-type mucosa. Detection of
      CDX2 in cardiac-type mucosa increased the likelihood of finding intestinal
      metaplasia in another biopsy set of columnar-lined oesophagus (odds ratio 3.5,
      95% CI = 1.2-10, P = 0.02). MUC2 was positive in 13 of 23 (57%) of CDX2-positive
      cardiac-type mucosa samples, whereas villin was detected in seven of 23 (30%).
      CONCLUSIONS: CDX2 expression in cardiac-type mucosa might be able to predict the
      presence of undetected intestinal metaplasia in columnar-lined oesophagus, and
      thus may be a putative marker for the presence of intestinal metaplasia in the
      absence of goblet cells.

PMID- 17206950
TI  - Determinants of compliance with colonoscopy in patients with adenomatous colon
      polyps in a veteran population.
AB  - AIM: To determine factors affecting compliance of a follow-up colonoscopy in
      patients with previously diagnosed adenomatous colon polyps. METHODS: A
      retrospective review was performed on patients with adenomatous polyps excised
      between January and December 1998. Twenty-nine clinical factors were assessed in
      patients grouped into whether they were compliant (n = 81) or noncompliant (n =
      38) with follow-up colonoscopy. Significant variables by univariate analysis were
      included in multivariate regression. RESULTS: One hundred and nineteen patients
      with adenomatous colon polyps were identified. Of 119 patients, 114 had a
      documented recommendation for follow-up of 5 years or less, with 69% having been
      compliant. In a univariate analysis, greater number of polyps (P = 0.04), NSAID
      use (P = 0.02), statin use (P = 0.005), first-degree relatives with colon cancer
      (P = 0.05) and compliance with out-patient clinic follow-up (P < 0.001) were
      significantly associated with patient compliance. Multivariate analysis revealed
      statin use (P = 0.05), first-degree relatives with colon cancer (P = 0.06) and
      compliance with out-patient clinic follow-up (P < 0.001) were independent
      predictors of compliance. CONCLUSIONS: History of statin use and family history
      of colon cancer are good predictors of compliance. The strongest predictor can be
      anticipated with compliance assessed with encounters for other visits. Strong
      efforts should be directed at improving patient education about colon cancer by
      the physician and facilitating patient compliance.

PMID- 17206951
TI  - Letters to the editors.

PMID- 17206953
TI  - Best Practice Guidelines on Publication Ethics: a publisher's perspective.
AB  - These Best Practice Guidelines on Publication Ethics describe Blackwell
      Publishing's position on the major ethical principles of academic publishing and
      review factors that may foster ethical behavior or create problems. The aims are
      to encourage discussion, to initiate changes where they are needed, and to
      provide practical guidance, in the form of Best Practice statements, to inform
      these changes. Blackwell Publishing recommends that editors adapt and adopt the
      suggestions outlined to best fit the needs of their own particular publishing
      environment.

PMID- 17206958
TI  - The epidemiology of preterm labour--why have advances not equated to reduced
      incidence?
AB  - The major burden of preterm birth is in the developing world, where most of the
      increasing death and morbidity is secondary to infectious diseases such as
      malaria, HIV, tuberculosis, bacterial vaginosis and intestinal parasites. In some
      developing countries, the growth of medical care has outstripped the growth of
      preventive public health, with an associated increase in iatrogenic preterm
      births. In developed countries, more than one-third of preterm births are
      medically indicated because of conditions such as fulminating pre-eclampsia or
      severe intrauterine growth restriction. Neither of these conditions is currently
      preventable. One in five preterm births is associated with multiple pregnancy,
      and these have been greatly increased by assisted reproduction techniques. The
      use of tocolytics has proved disappointing perhaps because inflammation rather
      than spontaneous uterine activity is increasingly recognised as the final common
      pathway. Inappropriate antibiotics used late in pregnancy are ineffective and may
      have adverse effects. Currently, the most promising interventions are public
      health related and include reducing the transmission of communicable diseases,
      improvements in the management of diabetes and reduction in harmful behaviours
      such as smoking and drug abuse.

PMID- 17206959
TI  - The cost of preterm birth: the low cost versus high value of tocolysis.
AB  - The consequences of preterm birth (PTB), to the individual and society at large,
      remain a major financial and personal burden. Babies born at the limits of
      viability, who survive, often have major neurological impairments, such as
      cerebral palsy, developmental delay and blindness. The cost of initial
      hospitalisation is more than $200,000 for each birth but takes no account of
      future costs once they leave the hospital. The major morbidities associated with
      extreme prematurity are respiratory distress syndrome (RDS), intraventricular
      haemorrhage (IVH) and necrotising enterocolitis (NEC). With advancing gestational
      age at birth, the financial costs and morbidity associated with these conditions
      decrease. The major morbidities (RDS, IVH and NEC) are rare by 34 weeks of
      gestation, with the exception of RDS, which complicates 7% of deliveries at this
      gestational age. While the vast majority of infants survive the first year of
      life, the infant mortality rate is markedly increased by three- to five-fold even
      for the mildly preterm infants, as compared with that of the term infants.
      Neonates born after 34 completed weeks of gestation rarely have mortality or
      major morbidity, but the financial costs remain significant ($7000 per case), and
      efforts to prevent delivery at this gestational age are probably indicated.
      Economic costs associated with PTB include the cost of initial hospitalisation,
      the cost of any chronic diseases resulting from the prematurity and social costs
      including loss of gainful employment by a family member taking care of the infant
      or child and loss of potential future earnings of the affected child. Antenatal
      steroids, if given to the mother at least 48 hours prior to a PTB, have shown
      significant reductions in RDS, IVH and NEC. Efforts to prevent, or avoid, PTB
      include the use of tocolytic agents which have been shown to prolong gestation
      for a minimum of 48 hours, or longer in some cases. The range of tocolytic agents
      used to delay or prevent PTB work through many different pathways, with varying
      degrees of success. Which tocolytic agent to use depends on many factors
      including underlying maternal status, gestational age of the fetus and documented
      efficacy of agent used.

PMID- 17206960
TI  - EPICure: facts and figures: why preterm labour should be treated.
AB  - The principal objective of the EPICure studies was to determine both short- and
      long-term outcomes of extremely preterm birth. Data were collected for all births
      before 26 completed weeks of gestation in the UK and Republic of Ireland for 10
      months in 1995. Of 811 infants admitted to neonatal units, 314 (39%) survived. Of
      these, 283 (92%) were assessed at 2.5 years and 241 (78%) at 6 years, together
      with a comparator group selected from classmates in normal schools. At 6 years,
      32 (13%) of those assessed had disabling cerebral palsy and 31 (13%) had severe
      sensory impairment. Cognitive impairment was a more frequent adverse outcome: the
      mean intelligence quotient (IQ) was 82 (SD 19). Fifty children (21%) had IQs > 3
      SD less than that of the comparator group, and in 48 children (20%), IQ was 2-3
      SD less than that of the comparator group. Infants whose mothers had received
      antenatal steroids had fewer severely abnormal head scan findings. In this
      population, abnormal head scan findings are independent predictors of reduced,
      severe motor disability at 2.5 years. Using step-wise logistic regression
      analysis, postnatal transfer was associated with severe motor disability;
      prolonged membrane rupture with reduced Mental Development Index (MDI) and
      antenatal steroid with increased MDI. It is clear that factors around the time of
      birth are critical in determining outcome, irrespective of later complications
      during neonatal intensive care. Since 1995, there is good evidence of improved
      survival, but it is not clear whether or not the number of survivors with severe
      adverse outcomes has changed. A new cohort of births <27 completed weeks is
      currently being collected in English maternity units. Data collection around the
      time of birth is more detailed than in 1995 in order to better explore the
      relationship between perinatal factors and later outcomes.

PMID- 17206961
TI  - Management of the neonate at the limits of viability: the Dutch viewpoint.
AB  - Due to ever-improving medical technology over the course of the last century, the
      limit of viability has been lowered from around 32 weeks of gestation, first to
      28 weeks and, in recent decades, to as low as less than 24 weeks. Long-term
      follow-up studies (Project on Preterm and Small-for-Gestational-Age Infants,
      Leiden Follow-up Project on Prematurity, Epidemiological Project for ICU Research
      and Evaluation, Etude Epidemiologique sur les Petits Ages Gestationnels,
      Extremely Preterm Infants in Belgium), however, have shown high percentages of
      deaths and/or disabilities at lower gestational ages in surviving children. Many
      parents and children are burdened with lifelong iatrogenic disabilities. As a
      result, the Dutch Paediatric Association and the Dutch Society of Obstetrics and
      Gynaecology have laid down joint rules for the management of expected/threatened
      preterm delivery.

PMID- 17206962
TI  - The preterm parturition syndrome.
AB  - The implicit paradigm that has governed the study and clinical management of
      preterm labour is that term and preterm parturition are the same processes,
      except for the gestational age at which they occur. Indeed, both share a common
      pathway composed of uterine contractility, cervical dilatation and activation of
      the membranes/decidua. This review explores the concept that while term labour
      results from physiological activation of the components of the common pathway,
      preterm labour arises from pathological signalling and activation of one or more
      components of the common pathway of parturition. The term "great obstetrical
      syndromes" has been coined to reframe the concept of obstetrical disease. Such
      syndromes are characterised by: (1) multiple aetiology; (2) long preclinical
      stage; (3) frequent fetal involvement; (4) clinical manifestations that are often
      adaptive in nature; and (5) gene-environment interactions that may predispose to
      the syndromes. This article reviews the evidence indicating that the pathological
      processes implicated in the preterm parturition syndrome include: (1)
      intrauterine infection/inflammation; (2) uterine ischaemia; (3) uterine
      overdistension; (4) abnormal allograft reaction; (5) allergy; (6) cervical
      insufficiency; and (7) hormonal disorders (progesterone related and
      corticotrophin-releasing factor related). The implications of this conceptual
      framework for the prevention, diagnosis, and treatment of preterm labour are
      discussed.

PMID- 17206963
TI  - The role of inflammation in preterm birth--focus on periodontitis.
AB  - It is universally accepted that acute inflammation is responsible for a
      substantial fraction of preterm births, particularly early cases. Much of this
      inflammation is caused by intrauterine infection. There is also evidence that
      infection and perhaps inflammation remote from the genitourinary tract can
      trigger preterm labour. Several studies have suggested that periodontitis during
      pregnancy increases the risk of preterm birth. Periodontitis may cause preterm
      birth by causing low-grade bacteraemia, which lodges in the decidua, chorion and
      amnion or by releasing endotoxin into the maternal circulation, which triggers
      intrauterine inflammation and preterm birth. Alternatively, it may release
      cytokines and other inflammatory products, which then trigger preterm labour. It
      is also conceivable that periodontitis might serve as a marker for other
      unhealthy behaviours, or immune hyperresponsiveness and that hyperresponsiveness
      to low-grade intrauterine infection itself might cause preterm birth. Currently,
      there are few data available to distinguish these possibilities. Such
      distinctions are important since they have clear implications for whether
      treatment of periodontitis might reduce the incidence of preterm birth. Several
      clinical trials of treatment of periodontitis are continuing, but until their
      results are known there is currently little evidence that treatment of
      periodontitis during pregnancy reduces the incidence of preterm birth.

PMID- 17206964
TI  - Aetiology of preterm labour: bacterial vaginosis.
AB  - Bacterial vaginosis (BV) is a common condition characterised by a polymicrobial
      disorder, with an overgrowth of several anaerobic or facultative bacteria and
      with a reduction or absence of lactobacillus colonisation. The prevalence of BV
      ranges from 4 to 64%, depending on the racial, geographic and clinical
      characteristics of the study population. In asymptomatic women, the prevalence
      varies from 12 to 25%, and similar percentages are observed in pregnant women.
      Although BV is associated with several adverse outcomes, such as upper genital
      tract infections, pelvic inflammatory disease, endometritis, preterm birth and
      low birthweight, many basic questions regarding the pathogenesis of BV remain
      unanswered. Mucosal immune system activation may represent a critical determinant
      of adverse consequences associated with BV. An unequal risk for BV acquisition
      and?or recurrence could derive from different mucosal immune host abilities
      and?or capability of invading microbes to produce factors that inactivate the
      local immune response. BV is associated with a two-fold increased risk of preterm
      birth, with the greatest risk when BV is present before 16 weeks of gestation
      (odds ratio = 7.55). This may indicate a critical period during early gestation
      when BV-related organisms can gain access to the upper genital tract and set the
      stage for spontaneous preterm labour later in gestation. The results of treatment
      trials for pregnant women with BV have been heterogeneous, with anywhere from an
      80% reduction to a two-fold increase in preterm birth among women who received
      treatment. For this reason, in current clinical practice significant controversy
      surrounds determining not only who and when to screen but also who and how to
      treat. Recent evidence shows that individual genetic backgrounds can affect
      chemokine production. This is an interesting area for future research and could
      lead to trials of treatment only for women genetically predisposed to preterm
      birth.

PMID- 17206965
TI  - Preterm birth: the value of sonographic measurement of cervical length.
AB  - Transvaginal ultrasound scanning of cervical length at approximately 20 weeks of
      gestation in women attending for routine antenatal care is useful for predicting
      the likelihood of spontaneous early preterm birth. The risk of early birth
      increases exponentially with decreasing cervical length in both singleton and
      multiple pregnancies. In such women, individualization of risk would lead to
      rationalisation of antenatal care, including frequency of visits, patient
      education in recognising and reporting symptoms of spontaneous preterm labour and
      timely administration of steroids. It is also possible that in women identified
      as being at high risk, the rate of preterm birth might be reduced by the
      prophylactic use of progesterone. In women presenting with threatened spontaneous
      preterm labour, transvaginal measurement of cervical length provides a useful
      distinction between those who are likely to deliver within the subsequent 7 days
      and those who are not. Since only 10-20% of such women are in true spontaneous
      preterm labour, the cervical length measurement in rational care can avoid the
      current practice of hospitalisation and administration of steroids and tocolytics
      to all. This article reviews the evidence in support of the clinical introduction
      of transvaginal sonography for both the prediction and management of spontaneous
      preterm labour.

PMID- 17206966
TI  - Should every unit have a 24-hour transvaginal ultrasound available?
AB  - The purpose of this debate is to argue the merits of whether the availability of
      24-hour transvaginal ultrasound service in every unit will help predict and,
      subsequently, prevent preterm birth. Any new test introduced will need to fulfil
      certain criteria. It must be acceptable in terms of risk, cost and patient
      convenience. It must be an improvement over existing alternatives, and it must
      aid clinicians to improve care. While the 24-hour availability of transvaginal
      ultrasound to every maternity unit may be useful to research and teaching, there
      is, as yet, little evidence that a 24-hour transvaginal ultrasound service
      improves perinatal and maternal morbidity and mortality. Results from our own
      centre suggest that experienced clinicians can make an acceptable diagnosis of
      spontaneous preterm labour (PTL) using only history and digital examination.
      Based on these findings, the availability of 24-hour vaginal ultrasound in every
      unit cannot be justified for the diagnosis of spontaneous PTL.

PMID- 17206967
TI  - Diagnosis of early preterm labour.
AB  - While preterm contractions occur almost as often extremely preterm as they do
      closer to term, birth due to spontaneous preterm labour before 27 weeks of
      gestation is rare, accounting for 0.05-0.7% of all births in different
      populations. Although the likelihood that uterine contractions before 27 weeks of
      gestation represent true preterm labour is low, the risk of adverse outcome in
      such cases is high. A correct diagnosis is important, and a useful diagnostic
      test should have a high sensitivity. In most reports, only 30-40% of women
      hospitalised for spontaneous preterm labour experience a preterm birth,
      suggesting a low positive predictive value of clinical diagnosis based on uterine
      contractions and vaginal examination. Transvaginal ultrasonographic scanning
      (TVUSS) of cervical length has shown a high sensitivity for preterm birth, 90
      100% for preterm birth before 33-35 weeks, using a liberal cutoff at 30 mm.
      Assessment of cervicovaginal fetal fibronectin (FFN) levels has shown a
      sensitivity of about 80%. Adding FFN assessment to TVUSS might contribute
      insignificantly to the prediction of preterm birth. In a retrospective study of
      147 women with spontaneous preterm labour and intact membranes before 27 weeks in
      our department, 61% of hospitalised women and 77% of women receiving tocolytic
      infusion therapy delivered before 32 weeks. Among 66 singleton pregnancies
      delivered before 32 weeks, at admission, 94% either had an effaced cervix or
      cervix with >/=2 cm dilation (74%), vaginal bleeding (61%) or serum C-reactive
      protein level >20 mg/l (40%), whereas one of these findings only was present in
      18% of women who delivered at later gestations. Among 132 women with symptoms of
      spontaneous preterm contractions before 27 weeks not admitted for hospital care,
      only 2 (1.5%) delivered before 32 weeks, not significantly higher than for all
      other women (0.6%). Although TVUSS may be useful when the diagnosis of
      spontaneous preterm labour is in doubt, the main predicament in early spontaneous
      preterm labour may not be to predict preterm birth but to prevent it, since many
      women appear in advanced labour or with manifest chorioamnionitis.

PMID- 17206968
TI  - Does assisted reproduction technology, per se, increase the risk of preterm
      birth?
AB  - There is little doubt that all methods of assisted reproduction increase the
      likelihood of multiple pregnancy and, as a result, increase the likelihood of
      preterm birth. Data from the East Flanders Prospective Twin Study clearly show
      that the proportion of spontaneous to iatrogenic twins has changed from 25:1 to
      1:1 over the past two decades. Data from the very low birthweight (VLBW) Infant
      Database of the Israel Neonatal Network showed that 10% of VLBW singletons were a
      result of assisted reproduction compared with 60% of the VLBW twins and 90% of
      the VLBW triplets. Irrespective of plurality, an association between preterm
      birth and assisted reproduction has long been suspected and was related to causes
      such as iatrogenic preterm birth (in the so-called 'premium' pregnancies),
      fertility history, past obstetric performance and to underlying medical
      conditions of the female partner. With more data available, a clearer picture is
      defined. Two different, recent meta-analyses showed that singleton pregnancies
      resulting from in vitro fertilisation (IVF) have increased rates of preterm birth
      at <33 weeks of gestation (OR 2.99; 95% CI 1.54-5.80), at <37 weeks of gestation
      (OR 1.93; 95% CI 1.36-2.74) and a relative risk of 1.98 (95% CI 1.77-2.22) for
      preterm birth in singleton pregnancies resulting from in vitro fertilisation
      embryo transfer/gamete intra fallopian transfer (IVF-ET/GIFT) compared with
      naturally conceived pregnancies. Since there is no way to predict which pregnant
      woman is at increased risk of preterm birth, it may be advisable to consider all
      pregnancies after assisted reproduction as being at risk. In any case, the most
      appropriate endpoint after assisted reproduction should also include preterm or
      term birth as measure of success.

PMID- 17206969
TI  - Use of tocolytics: what is the benefit of gaining 48 hours for the fetus?
AB  - Preterm birth remains one of the serious problems in perinatal medicine and is
      associated with an increased risk of neonatal complications and long-term
      morbidity. Although each day that delivery is delayed between 22 and 28 weeks of
      gestation increases survival by 3%, since most spontaneous preterm labour occurs
      between 28 and 34 weeks of gestation, this is of secondary concern; the primary
      goal of delay is to improve the function of certain systems in the fetus and to
      balance the risks of a hostile intrauterine environment with the complications of
      extrauterine preterm life. Although there is a lack of definitive evidence that
      tocolytic drugs improve outcome following spontaneous preterm labour and preterm
      birth, there is ample evidence that tocolysis delays delivery for long enough to
      permit administration of a complete course of antepartum glucocorticoids and to
      facilitate in utero transfer to a tertiary care unit where neonatal care will be
      optimal. Both these measures have been associated with improved outcomes;
      antepartum glucocorticoids reduce the incidence of respiratory distress syndrome,
      intraventricular haemorrhage, periventricular leucomalacia and necrotising
      enterocolitis, and in utero transfer is associated with decreased morbidity and
      mortality and less hospital-based intervention compared with postnatal
      transportation. Consequently, women who are more likely to benefit from tocolysis
      are those at early gestational ages, those needing transfer to a hospital that
      can provide neonatal intensive care and those who have not yet received a full
      course of antepartum glucocorticosteroids. In these cases, delaying labour for at
      least 48 hours with drugs such as atosiban should be considered, since it offers
      clear advantages for the fetus.

PMID- 17206970
TI  - Use of tocolytics: what is the benefit of gaining even more time?
AB  - Today's dogma states that tocolytics can be used to prolong pregnancy for just 48
      hours, allowing corticosteroids to be administered and transportation of the
      mother to a tertiary care centre. Surveys have shown that up to 30% of
      practitioners use maintenance tocolysis. Theoretically, maintenance tocolysis
      should be able to improve neonatal outcome by avoiding preterm birth and allowing
      delivery in the community maternity hospital or even at home, minimising social
      difficulties created by long distances between the mother and/or her baby and the
      rest of the family. This should result in fewer neonatal intensive care unit
      admissions, less respiratory distress syndrome and fewer long-term neurological
      sequelae. Such an effect has never been proven, probably because we do not know
      which women benefit from treatment, which do not require treatment because they
      are not in labour and which babies would better be born because chorioamnionitis
      and other insults jeopardize intrauterine development. Most studies on long-term
      tocolysis have been performed with beta-agonists. No improvement has been shown.
      On the contrary, a trend towards fetal harm with an increased risk for
      periventricular leucomalacia exists. Results from studies of one tocolytic should
      not be generalised; one published study on maintenance therapy with atosiban
      showed prolonged uterine quiescence and prolonged gestation, but was too small to
      detect differences in neonatal outcome. In the future, we need larger studies,
      not only to detect whether long-term tocolysis with newer tocolytics (oral
      oxytocin antagonists, prostaglandin receptor blockers) results in better neonatal
      outcome, especially at the lower gestational ages but also to discover methods
      that allow us to identify those women who will benefit from treatment and those
      for whom prolongation of pregnancy may cause harm.

PMID- 17206971
TI  - Mode of delivery in the early preterm infant (<28 weeks).
AB  - Elective caesarean section for women in labour with an immature baby might reduce
      the chances of fetal or neonatal death, but might also increase the risk of
      maternal morbidity. A review (updated in February 2004) of randomised trials
      comparing a policy of elective caesarean section versus expectant management with
      recourse to caesarean section produced six studies involving only 122 women.
      Differences in fetal outcome did not reach significance, but mothers undergoing
      elective caesarean section were more likely to have serious morbidity.
      Scientifically, the evidence remains inadequate. Clinically, the recommendation
      is that prematurity is not, in itself, an indication for caesarean section. In a
      survey from Israel, published in December 2004, of 2955 very low birthweight
      infants born at 24-34 weeks of gestation, the overall caesarean section rate was
      51.7%, and the mortality rate among babies prior to discharge was lower after
      caesarean section (13.2 versus 21.8%). After adjustment using multiple logistic
      regression, caesarean section had no effect on survival except in a subgroup with
      amnionitis, and it was again concluded that caesarean section cannot be routinely
      recommended unless there are other indications. A decision model developed in the
      USA has compared costs and health outcomes of two options for managing labour at
      24 weeks of gestation. The probabilities of both intact survival (16.8 versus
      12.9%) and survival with major morbidity (39.2 versus 19.4%) are higher with
      willingness to perform caesarean section, but less aggressive management is the
      more cost-effective strategy. Large studies are few and recruitment to such
      studies is perceived as a major problem. For clinicians, the decision will be
      influenced by local circumstances.

PMID- 17206972
TI  - Setting up a preterm prevention clinic: a practical guide.
AB  - In gynaecology, specialist menopause, urogynae, colposcopy, infertility, pelvic
      pain and cancer, rapid access clinics exist at many teaching and busy district
      general hospitals in the UK. Similarly, in obstetrics many busy maternity units
      have fetal medicine clinics, dedicated twins clinics and maternal medicine
      clinics, incorporating various general medical conditions and conditions
      peculiarly appropriate to pregnancy such as haematological disorders, diabetes
      and epilepsy. In contrast, in very few hospitals is there a dedicated clinic for
      women at increased risk of preterm birth, yet this is the major cause of neonatal
      mortality and morbidity in the developed world. Such a situation may be due to
      the confusion created by the fact that preterm birth is a heterogeneous condition
      with multiple aetiologies and hence multiple therapeutic interventions. It is
      possible to identify a group of women at particularly high risk of preterm birth
      in whom screening and interventional techniques have the potential to reduce the
      mortality and morbidity associated with spontaneous preterm labour and preterm
      birth.

PMID- 17206973
TI  - The quality of randomised trials of tocolysis.
AB  - Tocolytic treatment of suspected preterm labour has been evaluated in at least 75
      randomised controlled trials. These have been included in six Cochrane reviews.
      If the trials are poorly designed, such reviews may mislead or, at best, provide
      weaker evidence than those based on well-designed ones. The objective of this
      study was to compare the quality of the trials included in the Cochrane reviews
      of tocolytic therapy. Trial group sizes; the methods used by each trial to avoid
      selection, performance, attrition, and detection bias; and evidence that the
      statistical analysis plan was prespecified were abstracted from each Cochrane
      review. Except where noted, the judgement of the Cochrane reviewers was used. The
      number of trials graded A (sealed envelopes or third-party randomisation) for
      allocation concealment was as follows: beta-agonists 5/16, magnesium sulphate
      9/23, oxytocin receptor antagonists 6/6, cox inhibitors 12/13, calcium channel
      blockers 9/12, and nitric oxide donors 5/5. The number blinding the intervention
      was as follows: beta-agonists 9/16, magnesium sulphate 2/23, oxytocin receptor
      antagonists 5/6, cox inhibitors 7/13, calcium channel blockers 0/12, and nitric
      oxide donors 1/5. The number reporting a sample size calculation was as follows:
      beta-agonists 2/16, magnesium sulphate 3/23, oxytocin receptor antagonists 6/6,
      cox inhibitors 4/13, calcium channel blockers 4/12, and nitric oxide donors 1/5.
      The mean sample size of each treatment group was as follows: beta-agonists 53,
      magnesium sulphate 41, oxytocin receptor antagonists 126, cox inhibitors 31,
      calcium channel blockers 43, and nitric oxide donors 46. Data on avoiding
      attrition bias (follow-up rates) are difficult to summarise because there is no
      agreed standard for 'complete follow up'. Data on avoiding detection bias
      (blinding of outcome assessments) appeared unreliable because reviewers reported
      this in different ways. In conclusion, the trials of oxytocin antagonists and
      beta-agonists were of the highest quality. There remains considerable scope for
      bias in many of the trials included in the current Cochrane systematic reviews of
      tocolytics.

PMID- 17206974
TI  - A quality assessment tool to evaluate tocolytic studies.
AB  - Over the past 15 years, the use of beta-agonists has declined worldwide.
      Following the Royal College of Obstetricians and Gynaecologists guidelines in
      2002, clinicians in the UK and beyond were faced with the dilemma of continuing
      to use beta-agonists, desist from using tocolytic therapy completely or choosing
      to change to atosiban or calcium channel blockers (CCBs). While grade A level 1
      evidence exists to show that atosiban is significantly more efficacious than
      placebo and significantly safer than beta-agonists for the treatment of
      spontaneous preterm labour, the evidence for CCBs, such as nifedipine, is much
      less robust and no placebo-controlled trials have been performed. Published
      studies on nifedipine are largely investigator-led studies of small sample size,
      which lack sufficient power. As a result, most of the evidence has been based on
      meta-analyses of these studies, which look retrospectively at pooled data and are
      only as good as the quality of the studies included. In light of this, a tool was
      developed to produce a systematic review of studies on tocolytic effectiveness,
      which can and should be applied to all tocolytics and which considered both
      method- and topic-specific markers of quality. In the process of applying this
      tool to nifedipine, an extensive literature search identified 31 studies for a
      systematic review of the quality of nifedipine studies assessed by eight paired
      reviewers with wide experience in the subject of spontaneous preterm labour and
      preterm birth. Forty topic- and method-specific items of quality were assessed.
      The paucity of good quality studies of nifedipine used for the treatment of
      spontaneous preterm labour should be highlighted in meta-analyses or systematic
      reviews, which measure efficacy and should limit and influence the degree to
      which recommendations and guidelines are made on the basis of such studies.

PMID- 17206975
TI  - Regulatory and methodologic challenges to tocolytic development.
AB  - The development of tocolytic medications faces challenges common to all drug
      development programmes, principally related to evolving understanding of the
      pathophysiology. There are unique impediments to drug development for pregnancy
      related conditions in general and for tocolysis in particular. The purpose of
      this brief overview is to familiarize the obstetrician with the current
      challenges to drug development, focusing in particular on the problems of
      tocolytic development. A strategy for encouraging drug development for preterm
      labour and for pregnancy-related problems in general is presented.

PMID- 17206976
TI  - Clinical practice evaluation of atosiban in preterm labour management in six
      European countries.
AB  - OBJECTIVE: To evaluate the efficacy and safety of early administration compared
      with standard administration of atosiban, when predefined eligibility criteria
      were met. DESIGN: A prospective, open-label, randomised clinical trial. Women
      were randomised to receive atosiban either immediately (early) or when specified
      criteria, in terms of duration/frequency of uterine contraction or status of
      cervical dilation/effacement, were fulfilled (standard). SETTING: Carried out at
      105 centres in six European countries. POPULATION: Pregnant women admitted to
      hospital in threatened preterm labour between 24 and 34 weeks of gestation,
      comprising a subgroup of women enrolled in the Tractocile Efficacy Assessment
      Survey in Europe (TREASURE) clinical experience review. MAIN OUTCOME MEASURES:
      Efficacy was defined as the successful delay of delivery with no alternative
      tocolytic agent for 48 hours. RESULTS: More women in the early group remained
      undelivered at 48 hours with no alternative tocolytic agent compared with those
      who received atosiban when specified criteria were fulfilled (88.9 versus 76.1%;
      P = 0.03). Safety was comparable between the groups. There were no statistical
      differences in maternal, fetal or neonatal adverse events between the early and
      standard atosiban arms. CONCLUSIONS: The use of atosiban was effective for the
      delay of preterm labour and presented no safety concerns irrespective of the time
      it was administered.

PMID- 17206977
TI  - Continuing challenges in treating preterm labour: preterm prelabour rupture of
      the membranes.
AB  - Preterm prelabour rupture of the membranes (PPROM) is defined as prelabour
      rupture of the membranes prior to 37 weeks of gestation. It occurs in
      approximately 3% of pregnancies and is responsible for one-third of all preterm
      births. Effective treatment relies on accurate diagnosis, and it is gestational
      age dependent because the potential complications change with gestational age.
      Diagnosis itself is made by clinical suspicion, patient history and simple
      testing. Studies have shown that if a combination of patient history, nitrazine
      testing and ferning was used, the accuracy of at least two positive tests was
      93.1%. PPROM is associated with significant maternal and neonatal morbidity and
      mortality from infection, umbilical cord compression, placental abruption and
      preterm birth. Subclinical uterine infection has been implicated as a major
      aetiological factor in the pathogenesis and subsequent morbidity associated with
      PPROM and antenatal antibiotics, together with corticosteroid therapies, have
      clear benefits and should be offered to all women without contraindications.
      Women with PPROM after 32 weeks should be considered for delivery, and after 34
      weeks of gestation the benefits of elective delivery appear to outweigh the
      risks. Here, two cases are discussed that were experienced in our unit.

PMID- 17206978
TI  - Emerging tocolytics for maintenance therapy of preterm labour: oxytocin
      antagonists and calcium channel blockers.
AB  - The incidence of spontaneous preterm labour and preterm birth has increased, and
      its management worldwide remains suboptimal. While considerable debate remains as
      to whether long-term maintenance tocolysis is appropriate after an episode of
      spontaneous preterm labour, many practitioners support its use. Several drugs
      have been used for maintenance tocolysis, but they differ in terms of safety and
      efficacy. Atosiban and nifedipine are preferable for maintenance tocolysis, as
      they have been shown to be as effective as ritodrine while being associated with
      fewer adverse effects. Nifedipine is not licensed for use as a tocolytic. An
      ideal tocolytic should be utero specific, with few fetomaternal and fetal adverse
      effects, and should significantly improve perinatal outcome. To warrant the use
      of maintenance therapy, larger trials in women at particular gestational age
      ranges may be needed, in which the primary endpoints are perinatal outcomes. The
      inclusion of cost-effectiveness analyses would also be of benefit.

PMID- 17206979
TI  - 'Normal' pregnancy with adverse events on initial tocolytic treatment.
AB  - Preterm birth is never low risk and there are advantages gained by prolonging
      gestation even at relatively advanced stages of pregnancy. This means that high
      value treatments should not just be reserved for high-risk pregnancies. Some
      women treated with tocolytics will experience adverse events, and some adverse
      events are particularly associated with different classes of tocolytic agents.
      Cardiovascular adverse events are particularly common with beta-agonists and
      there have been several maternal deaths from pulmonary oedema as a result of beta
      agonist use for tocolysis. Calcium channel blockers are often associated with
      maternal hypotension, and a number of case studies reporting serious adverse
      events have been reported. The aim of this case study is to discuss what can be
      done if a patient experiences adverse events with tocolytics, and suggests
      approaches to continuing patient management and implications for obstetric
      practice.

PMID- 17206980
TI  - The use of high-dimensional biology (genomics, transcriptomics, proteomics, and
      metabolomics) to understand the preterm parturition syndrome.
AB  - High-dimensional biology (HDB) refers to the simultaneous study of the genetic
      variants (DNA variation), transcription (messenger RNA [mRNA]), peptides and
      proteins, and metabolites of an organ, tissue, or an organism in health and
      disease. The fundamental premise is that the evolutionary complexity of
      biological systems renders them difficult to comprehensively understand using
      only a reductionist approach. Such complexity can become tractable with the use
      of "omics" research. This term refers to the study of entities in aggregate. The
      current nomenclature of "omics" sciences includes genomics for DNA variants,
      transcriptomics for mRNA, proteomics for proteins, and metabolomics for
      intermediate products of metabolism. Another discipline relevant to medicine is
      pharmacogenomics. The two major advances that have made HDB possible are
      technological breakthroughs that allow simultaneous examination of thousands of
      genes, transcripts, and proteins, etc., with high-throughput techniques and
      analytical tools to extract information. What is conventionally considered
      hypothesis-driven research and discovery-driven research (through "omic"
      methodologies) are complementary and synergistic. Here we review data which have
      been derived from: 1) genomics to examine predisposing factors for preterm birth;
      2) transcriptomics to determine changes in mRNA in reproductive tissues
      associated with preterm labour and preterm prelabour rupture of membranes; 3)
      proteomics to identify differentially expressed proteins in amniotic fluid of
      women with preterm labour; and 4) metabolomics to identify the metabolic
      footprints of women with preterm labour likely to deliver preterm and those who
      will deliver at term. The complementary nature of discovery science and HDB is
      emphasised.

PMID- 17206981
TI  - Prematurity or immaturity?
AB  - Birth in the human is particularly difficult compared with that in the other
      primates. Bipedalism has evolved over the past 6 or 7 million years, and has
      resulted in a small pelvis, adapted to the upright posture. In recent millennia,
      the increasing size of the fetal head at birth has made childbirth difficult.
      Haig has suggested that the mother and fetus do not have identical interests; the
      baby benefits from being large at birth, while it is easier for the mother to
      deliver a small baby. Many of the 500 000 maternal deaths per year around the
      world are due to obstructed labour, especially in Africa. Even in London, black
      African women have the highest caesarean section rates. Black African babies are
      on average smaller than white European babies, due mainly to earlier delivery. In
      a 13-year study of births in North West Thames, African babies were 2.5 times
      more likely to be born between 24 and 31 weeks inclusive than white European
      babies. Between 33 and 38 weeks of gestation, black African babies behaved in a
      more mature way, are more likely to pass meconium and have jaundice, but less
      likely to have respiratory problems leading to admission to the special care baby
      unit. Preterm black African babies have lower gestation-specific perinatal
      mortality than white European babies, while at term and beyond the reverse is
      true. Preterm birth may have evolved partly as a response to disproportion.

PMID- 17206990
TI  - Opportunities for change: the future roles of the health library and information
      professional.

PMID- 17206982
TI  - The therapeutic use of rituximab in non-Hodgkin's lymphoma.
AB  - The non-Hodgkin's lymphomas (NHLs) comprise a heterogeneous collection of
      lymphoproliferative malignancies, which are most common in people aged over 55
      years. Diffuse large B-cell lymphoma (DLBCL) is the most common type of NHL,
      accounting for approximately 30% of all new patients. Follicular lymphoma (FL) is
      the second most common NHL sub-type, and accounts for a further 22% of cases.
      While the incidence of most other cancers is decreasing, that of NHL is
      increasing steadily. During the 1970's and 1980's, worldwide NHL incidence rose
      by 3-4% per year. This rise has slowed in the 1990's, but an annual increase of 1
      2% is still being recorded. Over the last five years, the introduction of
      monoclonal antibodies, and specifically the anti-CD20 monoclonal antibody,
      rituximab, has radically changed treatment of B-cell NHL. Rituximab is a
      genetically engineered chimeric mouse/human monoclonal antibody which binds to
      the transmembrane antigen, CD20, a non-glycosylated phosphoprotein, located on
      pre-B and mature B lymphocytes. This antigen is expressed on over 95% of all B
      cell NHLs, and on normal B cells, but not on haematopoietic stem cells, normal or
      malignant plasma cells. The Fc domain of rituximab recruits immune effector
      functions to mediate B cell lysis. Possible mechanisms of cytotoxicity include
      complement-dependent cytotoxicity (CDC) resulting from C1q binding, and antibody
      dependent cellular cytotoxicity (ADCC) mediated by one or more of the Fcgamma
      receptors on the surface of granulocytes, macrophages and NK cells. It is also
      possible that the binding of rituximab to the CD20 antigen on the cell surface
      may directly induce apoptosis. For patients with both follicular and diffuse
      large B-cell NHL, several large scale prospective randomised trials have
      demonstrated prolongation of remission when rituximab is incorporated into first
      line treatment, and, in follicular lymphoma, as a component of salvage therapy.
      As a result of these studies, current European indications for rituximab include:
      the treatment of previously untreated patients with stage III-IV follicular
      lymphoma in combination with cyclophosphamide, vincristine and prednisone (CVP)
      chemotherapy; as maintenance therapy in patients with relapsed follicular
      lymphoma responding to induction therapy with chemotherapy or immuno
      chemotherapy; the treatment of patients with diffuse large B cell NHL in
      combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)
      chemotherapy. This paper examines the evidence supporting the use of rituximab in
      these settings, and places its use into the context of standard clinical
      practice.

PMID- 17206991
TI  - The context of change: information professionals and the information professions
      in an information society.

PMID- 17206992
TI  - What do clinicians want from us? An evaluation of Brighton and Sussex University
      Hospitals NHS Trust clinical librarian service and its implications for
      developing future working patterns.
AB  - BACKGROUND: The Clinical Librarian (CL) Service at Brighton was established in
      2003 with the aim of providing high-quality evidence to designated teams and
      fostering an evidence-based culture. OBJECTIVE: To evaluate the CL service at
      Brighton and discuss the implication of the findings. METHODS: A combination of
      internally collected data (n = 167), and an external evaluation of the service by
      questionnaires (n = 86) of users and non-users and interviews (n = 9) of users.
      RESULTS: Internal data suggest that the service is valued by its users and that
      patient care and continuing professional development are the most common uses for
      searches (confirmed by the external study); that searches generally result in
      some change in knowledge; and that this knowledge is disseminated. The external
      study found that visibility of the CL was crucial to the effectiveness of the
      role and that clinicians used the service mostly to get access to a wider range
      of resources and/or to save time. Users wanted the CL to include evaluative
      annotation with the results, and for the CL role to become more embedded in the
      team. Interview results expanded on the issues of integration of the CL and the
      need for annotation of results. CONCLUSIONS: To be most effective, CLs would be
      dedicated to one team, but financial constraints make this unlikely. Alternative
      working patterns are suggested as a possible compromise.

PMID- 17206993
TI  - Achieving change through mutual development: supported online learning and the
      evolving roles of health and information professionals.
AB  - INTRODUCTION: Major changes in health care, within an information- and technology
      rich age, are impacting significantly on health professionals and upon their
      education and training. Health information professionals-in both the National
      Health Service (NHS) and higher education (HE) contexts-are consequently
      developing their roles, skills and partnerships to meet the needs of flexible
      education and training. This article explores one facet of this-supported online
      learning and its impact on role development. METHODOLOGY: A case study approach
      was taken, aiming to explore how academics, health information professionals and
      learning technologists are developing supported online learning to explicitly
      address the e-literacy and information needs of health students within the
      context of NHS frameworks for education. This was contextualized by a literature
      review. RESULTS: The case study explores and discusses three dynamics--(i) The
      use of supported online learning tools by future health-care professionals
      throughout their professional training to ensure they have the appropriate e
      literacy skills; (ii) the use of supported online learning by current health
      professionals to enable them to adapt to the changing environment; (iii) the
      development of the health information professional, and particularly their role
      within multi-disciplinary teams working with learning technologists and health
      professionals, to enable them to design and deliver supported online learning.
      CONCLUSIONS: The authors argue that, in this specific case study, health
      information professionals are key to the development of supported online
      learning. They are working successfully in collaboration and their roles are
      evolving to encompass learning and teaching activities in a wider context. There
      are consequently several lessons to be drawn in relation to professional
      education and role development.

PMID- 17206994
TI  - Opportunity for change in the future roles for the health library and information
      professional: meeting the challenges in NHS Scotland.
AB  - BACKGROUND: NHS Education for Scotland (NES) is the Special Health Board
      responsible for supporting best practice in education, training and development
      for all staff groups within NHS Scotland. As part of its remit, the Knowledge
      Services Group within NES is responsible for the e-Library, a national electronic
      resource providing and supporting access to the evidence base. The Knowledge
      Services Group also supports the national development of library services to NHS
      Scotland. AIMS: This article aims to provide a reflective overview of some recent
      challenges within the health library and information field in Scotland, and the
      positive role opportunities these have afforded. METHODS: The information was
      gathered through extensive professional interaction with staff across the sector
      over the first year of establishing the new role of Librarian Staff Development
      Manager. FOCUS: New roles have emerged for health library and information
      professionals generally; for example, in response to new technology or new user
      groups. The development of the NHS Scotland e-Library provides examples of role
      development that emerges symbiotically from core skills applied to a new
      situation or applied in an innovative way. Role development among health library
      and information professionals operating at the local service level can be both
      reactive and proactive. Working together, the partnership between the national
      Knowledge Services Group and local library and knowledge services for NHS
      Scotland has resulted in the emergence of additional new roles, extending the
      role portfolio of the local professional (for example, the Librarian-Tutor role)
      and supported by other national infrastructures (for example, the competency
      framework initiative).

PMID- 17206995
TI  - Health check for Latvia: opportunities for information professionals in a new
      democracy.
AB  - BACKGROUND: This paper outlines developments in medical information in Latvia
      since independence from the former USSR in 1991, and analyses the health
      information gap faced by professionals. OBJECTIVES: To explore international
      initiatives and co-operation in health information provision in Latvia; to
      describe the activities of Latvian medical librarians at national, regional and
      international level; to look at health information provision by specialist
      information centres; and to discuss the role of librarians in health information
      provision in public libraries. METHODS: An extensive search was made of databases
      and medical library and health information centre staff were interviewed; a
      questionnaire survey of librarians was carried out. RESULTS: International
      initiatives and co-operation by medical librarians have extended their services
      at national, regional and international level. Health information portals exist,
      with online contacts and links to smaller health centres and organizations, but
      rarely employ qualified librarians or information professionals. Ninety-three per
      cent of public librarians had provided health information, with 79% using the
      Internet. The most popular sources of health information were magazines, books,
      local pharmacies and the Internet, but mostly for healthy lifestyle, not medical
      problems. CONCLUSIONS: E-health and medical informatics are high government
      priorities. Medical librarians are actively involved in these initiatives.

PMID- 17206996
TI  - Development of a Knowledge and Library Service in newly configured specialist
      mental health teaching trust-the first year.

PMID- 17206997
TI  - Workplace-based information skills outreach training to primary care staff.

PMID- 17206998
TI  - Stepping out: the changing role of e-resources librarians.

PMID- 17206999
TI  - Listening to our clinical colleagues: how are they finding their evidence to
      support Trust clinical governance?

PMID- 17207000
TI  - Signposting best evidence: a role for information professionals.

PMID- 17207002
TI  - Nurses' experiences of practice and political reform in long-term aged care in
      Australia: implications for the retention of nursing personnel.
AB  - AIM: The aim of the study was to explore registered nurses' experiences in long
      term aged care in light of the political reform of aged care services in
      Australia. BACKGROUND: In Australia, the aged care industry has undergone a
      lengthy period of political and structural reform. Despite reviews into various
      aspects of these reforms, there has been little consideration of the effect these
      are having on the practice experiences and retention of nursing staff in long
      term care. METHODS: In this critical hermeneutic study, 14 nurses from long-term
      care facilities in Australia were interviewed about their experiences during the
      reform period. RESULTS: The data revealed a sense of tension and conflict between
      nurses' traditional values, roles and responsibilities and those supported by the
      reforms. Nurses struggled to re-negotiate both their practice roles and values as
      the reforms were implemented and the system evolved. Nursing management support
      was an important aspect in mediating the effect of reforms on nursing staff.
      CONCLUSION: This research highlights both the tensions experienced by nurses in
      long-term aged care in Australia and the need to re-negotiate nursing roles,
      responsibilities and values within an evolving care system. This research
      supports a role for sensitive and proactive nursing management during periods of
      industry reform as a retention strategy for qualified nursing personnel.

PMID- 17207003
TI  - The role and scope of the clinical nurse consultant in Wentworth area health
      service, New South Wales, Australia.
AB  - AIMS: This paper reports phase one of a two-part study in a New South Wales area
      health service, which aimed to evaluate the grading system for clinical nurse
      consultants. BACKGROUND: Since its inception in 1986, the role and scope of
      practice of clinical nurse consultants in New South Wales has been viewed with
      differing expectations leading to role conflict from the nurse consultants
      themselves and others in health care including managers and other clinicians.
      METHOD: A quantitative approach was used for this study. A survey comprising of
      open and closed questions was mailed to all clinical nurse consultants (n = 42)
      employed in the area. RESULTS: The data presented suggest that ambiguity
      continues about the role, the scope and the differences within the grading system
      of clinical nurse consultants. CONCLUSIONS: Clinical nurse consultants need
      leadership training and support from their managers to fulfil their role. More
      work is required to clarify the role of clinical nurse consultants.

PMID- 17207004
TI  - Auditing the impact of implementing the Modern Matron role in an acute teaching
      trust.
AB  - AIM: This paper describes how an acute teaching trust established the role of
      Senior Nurses (Modern Matrons) and an audit that was undertaken 12 months after
      they were appointed to evaluate the role. BACKGROUND: The concept of the Modern
      Matron was introduced in 2000 and all trusts had to implement the role by April
      2002. METHODS: The audit comprised: measurement of progress against agreed
      corporate objectives and questionnaires to all senior nurses and a range of trust
      staff staff. RESULTS: The following themes were identified: Senior Nurse post,
      patient care, infection control and leadership. Senior nurses were found to be
      satisfied with their role and the preparation for and understanding of their role
      seemed to be successful. There were many improvements such as a reduction in drug
      errors, complaints and MRSA bacteriaemias. CONCLUSIONS: Implementation of the
      Modern Matron role has been successful and made improvements in patient care.

PMID- 17207005
TI  - Developing bed managers: the why and the how.
AB  - AIM: This paper describes and analyses the role of bed managers within hospitals,
      and how this can be supported through a development programme. BACKGROUND AND KEY
      ISSUES: Bed management has increased in importance as access targets have
      developed, and appreciation of the importance of patient flow has grown. The bed
      management role is usually performed by nurse managers, and can be particularly
      stressful and managerially complex. Despite calls for training support, little
      has been available. In response we have developed and delivered a training
      programme to over 70 staff in the past 2 years. EVALUATION AND CONCLUSIONS: The
      programme evaluation data is used to show that it has had an impact on the
      knowledge and skills of the bed managers involved, but also on their subsequent
      behaviours. These changes have translated into results for the organization and
      the individual, including staff retention, promotion and fewer cancelled
      operations. We conclude that the programme is an effective way to enhance the
      knowledge and skills of bed managers, and that the enhanced profile of bed
      management raises challenges for nurse managers in many areas of the
      organization.

PMID- 17207006
TI  - Quality improvement: the divergent views of managers and clinicians.
AB  - AIM: The aim of this study was to identify and explore nurse managers' and
      clinical nurses' perceptions of quality improvement as related to their practice.
      BACKGROUND: The quality improvement process has become an integral component of
      health care service delivery. The pivotal role that nurse managers and clinical
      nurses play in the success of quality improvement initiatives is consistently
      reported throughout the literature. Published evidence has primarily focused on
      nurses' perceptions of "quality" and the importance of the nurse's role. However,
      the literature fails to provide evidence that nurse managers and clinical nurses
      agree with this. METHOD: Research was conducted at one large regional hospital in
      Australia in the year 2000 and used a descriptive qualitative research
      methodology. Data were collected using semistructured interviews with six nurse
      managers and six clinical nurses on two consecutive occasions and analysed using
      constant comparative analysis. RESULTS: Nurse managers' and clinical nurses'
      understanding of the concept of quality improvement and how it applies to the
      practice of nursing differed. Each group identified that quality improvement can
      be beneficial to nursing practice, but blamed each other for potential benefits
      not being realized. Both nurse managers and clinical nurses offered similar
      solutions with varied emphasis on how quality improvement could improve nursing
      practice and patient outcomes. CONCLUSION: The quality improvement process
      requires review. Nurse managers and clinical nurses offered divergent views of
      the identified deficiencies in the way quality improvement is implemented that
      reduce its clinical impact. Integral to the success of any quality improvement
      process is the inclusion of views of both nurse managers and clinical nurses.

PMID- 17207007
TI  - Nurses' perceptions of quality assurance.
AB  - AIM: To describe nurses' perceptions of quality assurance. METHODS: A qualitative
      approach using phenomenography was adopted in this study. Data were collected by
      open and semi-structured interviews from a strategic sample of nurses (N = 10)
      from a hospital in the south-west of Sweden. FINDINGS: The nurses showed 10
      different perceptions of the phenomena, which were summarized into four
      description categories: controlling, development, cooperation and demands. The
      perceptions described show that nurses can perceive quality assurance both as an
      asset and as a burden. CONCLUSION: The expressed perceptions show that nurses use
      quality assurance as a way of keeping a certain level of caring. It also gives
      nurses an opportunity for professional growth as well as a possibility for
      rewards. Working together as a team, even though there are different staff
      grades, to find joint standpoints, has a positive effect not only on qualitative
      assurance but also for the patient, as he/she often meets different categories
      during hospital stay.

PMID- 17207008
TI  - Factors influencing the choice of the first ward: comparison between newly
      qualified nurses and managers.
AB  - We had given a questionnaire to a group of newly qualified nurses and nursing
      managers responsible for their recruitment with the purpose of understanding the
      factors influencing the choice of the first ward. For this study, 45 nurses and
      10 nursing managers had been recruited. There are 19 factors that influence the
      choice of the first ward: the most important is the kind of patient, both,
      nursing managers and newly qualified nurses agreed about, while about the other
      factors there were different answers. Reflecting on the choice factors may help
      hospitals to better understand the expectations of the newly qualified nurses and
      start improving projects to make even the less requested wards more attractive;
      it can also help the faculty to reflect about the academic curriculum that mostly
      influences the professional future of the students.

PMID- 17207009
TI  - 5-20: a model of minimum nurse-to-patient ratios in Victoria, Australia.
AB  - AIM: This study presents a critique of a new model of minimum nurse-to-patient
      ratio and considers its utility alongside established Patient Dependency Systems.
      BACKGROUND: Since 2001 legislation mandating minimum nurse-to-patient ratios has
      been enacted throughout large public hospitals in the state of Victoria,
      Australia. The Victorian model mandates minimum staffing of five nurses to 20
      patients in acute medical and surgical wards. In conjunction with this approach,
      Patient Dependency Systems are employed to anticipate short-term resource needs.
      KEY ISSUES: Although this legislation has been successful in attracting nurses
      back into the public sector workforce, no published empirical evidence exists to
      support specific ratios. In addition, neither ratio nor Patient Dependency
      Systems approaches account for the critical influence of skill mix on hospital,
      employee, or patient outcomes. CONCLUSION: There is an urgent need for further
      research that specifically examines relationships between models of staffing,
      skill mix and quality outcomes.

PMID- 17207010
TI  - Self-scheduling for hospital nurses: an attempt and its difficulties.
AB  - AIM: To describe a pilot project on self-scheduling (self-rostering) for hospital
      nurses and assess its potential values and difficulties in implementation.
      BACKGROUND: Self-scheduling is one aspect of the effort to make the hospital
      nursing environment more accommodative of nurses' lives. It is part of the good
      employment practices that nurses want and that can help recruitment, retention
      and--possibly--patient care. METHOD: A self-scheduling programme was implemented
      on one nursing floor for a year. Its effect on nursing perceptions was gauged by
      an informal questionnaire, and its effect on the nurse manager was gauged by
      counting change requests and sick calls, as well as her time spent on scheduling
      and her perceived annoyance in doing it. FINDINGS: During the time of the pilot
      project nurses felt that they had better control of their time and were able to
      give better patient care. Also, change requests decreased, as did the time spent
      by the nurse manager and her sense of annoyance. But since the nurses did not
      adhere to the rules of the programme, despite repeated efforts by the nurse
      manager, the attempt floundered. CONCLUSION: Self-scheduling can have positive
      results for nurses and benefit the nurse manager. But if nurses see this as an
      individual entitlement instead of a balance between individual and unit benefit,
      everyone loses. This experience may be of use to others trying to implement a
      self-scheduling system.

PMID- 17207011
TI  - Pilot exploration of the association between self-esteem and professional
      satisfaction in Hellenic hospital nurses.
AB  - AIM: To explore potential associations between nurses' self-esteem and
      professional satisfaction. BACKGROUND: Professional burnout and moderate job
      satisfaction have been reported consistently among nurses. However, potential
      associations of the above elements with personality characteristics have not been
      adequately addressed. METHODS: A random sample of 154 adult healthcare nurses
      completed the Maslach Burnout Inventory, the Berger's Scale and the Index of Work
      Satisfaction. Associations and comparisons across different settings and
      background variables were explored. RESULTS: Moderate to positive levels of self
      acceptance (mean Likert rating: 3.95 +/- 0.51) and acceptance-of-others (mean
      Likert rating: 3.7 +/- 0.43) and low to moderate levels of professional
      satisfaction (mean Likert rating: 3.69 +/- 0.63) were observed. Positive
      correlations were detected between professional satisfaction and self-esteem
      indices (r = 0.249-0.313, P < or = 0.008). A mediating effect of burnout was
      implied. CONCLUSIONS: A potential interaction between personality and
      professional attitudes of Hellenic Hospital nurses was observed. The present
      study is limited within the correlational frame. Further study is needed to
      investigate a potential causal relationship between self-esteem indices and
      professional satisfaction, in order to inform nursing retention and support
      policies.

PMID- 17207012
TI  - Enabling student placement through strategic partnerships between a health-care
      organization and tertiary institutions.
AB  - Nursing management needs to demonstrate its commitment to clinical education for
      undergraduate nursing students. The vision for the nursing leadership and
      management team at Princess Alexandra Hospital is to guide and support the
      development of hospital clinicians, at all levels in the organization, to
      effectively facilitate undergraduate students' learning during their clinical
      practical experiences. This paper examines the evolution of the meaning,
      commitment and practices that have been intrinsic to the development of strategic
      partnerships between the health-care organization and tertiary institutions to
      ensure that hospital staff who consistently facilitate student learning in the
      clinical context are well supported. The partnerships are based on open channels
      of communication between the health-care organization and the tertiary
      institutions whereby each party identifies its needs and priorities. This has
      resulted in increased hospital staff satisfaction through greater involvement by
      them in the placements of students, and enhanced understanding of clinicians of
      the student placement process that has contributed to improved satisfaction and
      outcomes for the students.

PMID- 17207013
TI  - A survey-based exploration of the impact of dyslexia on career progression of UK
      registered nurses.
AB  - AIM: To explore the effects of dyslexia on the practice and career progression of
      UK registered nurses (RN). BACKGROUND: Literature suggests dyslexia can have a
      negative impact in the workplace and may pose particular difficulties for nurses,
      where accuracy in information processing activities is essential for practice.
      METHODS: A questionnaire was used to survey RNs with dyslexia (n = 116) and
      results analysed using content analysis. FINDINGS: Dyslexia provided a challenge
      to the everyday work of RNs, which was often met successfully using a range of
      individualized strategies. Career progression was achievable but compared with
      peers, was perceived to take longer. Disclosure of dyslexia to work-colleagues
      was selective and dependent on the perceived benefits. Informal support
      mechanisms were commonly utilized with formal management support less well
      defined. CONCLUSION: Dyslexia appears to have a negative impact on working
      practices and career progression, but remains a poorly understood and often
      hidden disability.

PMID- 17207014
TI  - Challenges for new nurses in evidence-based practice.
AB  - AIM: The purpose of this article was to examine issues that new nurses encounter
      as they enter nursing practice, particularly in an evidence-based practice
      environment. BACKGROUND: These issues are not new. In part, these issues arise
      from our failure to acknowledge the developmental issues that new nurses
      experience on entry to practice and the lack of role models in evidence-based
      practice and holistic care. EVALUATION: This article synthesizes research
      reported over the last decade to delineate the issues of transition to practice
      and strategies that have proven effective in addressing them. KEY ISSUES: The key
      issues relate to the need to support new nurses in evidence-based and holistic
      practice, the strategies needed to do so, and the nurse manager's role in this
      process. CONCLUSIONS: We must invest resources in assisting new nurses into
      practice, which may have benefits in terms of both recruitment and retention of
      new nurses in practice.

PMID- 17207015
TI  - First-line nurse managers in university hospitals--captives to their own
      professional culture?
AB  - AIM: This study investigates whether first-line nurse managers in hospitals share
      common dispositions related to managerial work and leadership, what they are
      like, and what their relationship is with the various expectations set on them.
      METHODS: The first data were collected by focus group interviews in the autumn of
      2000 and analysed using qualitative content analysis and frame analysis. The
      second data set were part of a questionnaire survey addressed to the same
      managers in 2001 with a focus on their diverse leadership roles. RESULTS: Among
      first-line nurse managers, the management frameworks of a nurturing mother and an
      administrative nurse displayed the strongest prominence, and the emphasis seemed
      to be evolving towards the administrative. The results from the survey confirmed
      the findings of this study in relation to first-line nurse managers' management
      frameworks. CONCLUSION: The line of development found in this study may add to
      the permanence of operations and the stability of the operative culture at a
      university hospital. It may also diminish the opportunities for nursing
      development in university hospital wards and weaken the potential for a new kind
      of competence among both managers and their subordinates.

PMID- 17207019
TI  - Respirology year-in-review 2006: clinical science.

PMID- 17207020
TI  - Follow up and surveillance of the patient with lung cancer: what do you do after
      surgery?
AB  - Of the new cases of lung cancer discovered each year, it has been estimated that
      50-55% have localized disease and are thus candidates for potentially curative
      treatment. Some of these patients will refuse surgery or will have co-morbidities
      that preclude surgery. The remainder will undergo an attempted curative
      resection. A common clinical question arises in these patients: how should this
      patient be followed after surgery? Post-treatment surveillance is indicated to
      monitor for recurrence of the original tumor and for the development of a
      metachronous tumor. The appropriate protocol is controversial and current
      recommendations are primarily expert opinion or consensus-based and await further
      study. A suggested clinically reasonable and cost-effective surveillance approach
      would include a history, physical examination and an imaging study (either chest
      radiograph or CT) every 6 months for 2 years and then annually. Patients should
      be counselled on symptom recognition and advised to contact their physician
      should such symptoms appear.

PMID- 17207021
TI  - Proteomics analysis in lung cancer: challenges and opportunities.
AB  - Recent technological developments in proteomic analysis are bringing us new
      insights into the molecular classification of tumours. Although proteomic
      analysis in cancer profiling is still under development both in terms of the
      instruments used and the data analytical tools, this method has great potential
      advantages for the analysis of biospecimens of many types. Direct measurement of
      abnormally expressed or modified proteins in the tumour tissue and/or patient
      blood may be an effective approach for discovering new biomarkers. Proteomics has
      the significant advantage of being able to discern not only changes in expression
      levels but also in post-translational modifications. Thus, the proteomics
      approach to protein profiling and biomarker discovery uncovers biomarkers from a
      different viewpoint than microarray analysis. This review summarizes the range of
      proteomics technologies employed for cancer profiling, and how they have been
      used to derive new classification models for human lung cancer.

PMID- 17207022
TI  - Genetic analysis of CC16, OGG1 and GCLC polymorphisms and susceptibility to COPD.
AB  - BACKGROUND AND OBJECTIVES: The importance of genetic susceptibility in COPD has
      not been determined. The aim of this study was to investigate the association
      between susceptibility to COPD and polymorphisms in the Clara cell 16 kDa
      secretory protein (CC16), 8-hydroxy-guanine glycosylase (OGG1) and
      glutamatecysteine ligase catalytic subunit (GCLC) genes in a southern Chinese
      population of Han nationality. METHODS: A case-control study was performed on 166
      paired subjects with or without COPD, who were randomly selected from a pool of
      310 paired subjects. These subjects were selected from epidemiological survey
      participants, with matched-pairs being strictly localized in the Guangzhou urban
      and Shaoguan rural areas. The following polymorphisms were genotyped by PCR
      single strand conformation polymorphism analysis: 38 A/G in exon 1 of the CC16
      gene, 1245C/G in exon 7 of the OGG1 gene and -129C/T in the GCLC gene. Genotype
      frequencies and allelic frequencies were analysed. RESULTS: There were no
      significant differences in the distribution of genotype frequencies for CC16 38
      A/G, OGG1 1245C/G or GCLC -129C/T between the COPD and non-COPD subjects. The
      distribution of the allelic frequencies of these three genes also showed no
      significant difference between the two groups. CONCLUSIONS: The genetic
      polymorphisms in CC16 38 A/G, OGG1 1245C/G and GCLC -129C/T are not associated
      with susceptibility to COPD in a southern Chinese population of Han nationality.

PMID- 17207023
TI  - Intronic single-nucleotide polymorphisms in Bcl-2 are associated with chronic
      obstructive pulmonary disease severity.
AB  - BACKGROUND AND OBJECTIVE: COPD is a multifactorial disease influenced by genetic
      and environmental factors, and gene-by-environmental interactions. There is
      considerable variability in the degree of airflow obstruction, moreover only 10
      15% of chronic smokers develop COPD. These observations indicate that additional
      risk factors, possibly genetic, contribute to not only the susceptibility to COPD
      but also the development and severity of COPD. Recent paradigms highlight the
      presence and causal role of apoptosis in emphysema. There is a large amount of
      information on the genes involved in the regulation of apoptosis and one of the
      most studied is Bcl-2. The aim of this study was to investigate the genetic
      association of Bcl-2 gene with the level of lung function, that is, the severity,
      of COPD. METHODS: The genetic association of Bcl-2 polymorphisms with lung
      function was investigated in 261 Japanese patients with COPD using 12 single
      nucleotide polymorphisms (SNPs) in Bcl-2. RESULTS: Four SNPs showed a significant
      association between the high and low lung function groups in a dominant trait
      comparison. Subsequent linkage-disequilibrium mapping and analyses of haplotype
      structure also showed a significant association between the level of lung
      function and two haplotypes comprised of the associated SNPs in Bcl-2.
      CONCLUSIONS: Although the linkage between Bcl-2 gene and the susceptibility to
      COPD remains to be clarified, the findings of the current study indicate that Bcl
      2 might be influencing the level of lung function, that is, the development and
      severity of COPD.

PMID- 17207024
TI  - Association between the IL-4 promoter polymorphisms and asthma or severity of
      hyperresponsiveness in Taiwanese.
AB  - BACKGROUND AND OBJECTIVES: Recent family-based studies have revealed a linkage
      between human chromosome 5q31 and asthma, elevated serum IgE levels and airway
      hyperresponsiveness (AHR). Among the candidate genes in this region is the gene
      encoding IL-4. This gene could be a candidate gene for asthma. The aim of this
      prospective case-control study was to assess the frequency of polymorphisms in
      the IL-4 gene promoter among asthmatic patients from Taiwan. METHODS: The study
      consisted of 167 patients with asthma and 111 healthy subjects. PCR amplification
      followed by Bsm F1 restriction digestion were used to assign genotypes at the IL
      4 promoter C-589T locus. Pulmonary function tests, methacholine challenge tests,
      total IgE, specific IgE antibodies against common inhalant allergens and total
      eosinophil counts were assessed in asthmatic patients. RESULTS: The T allele
      frequency for the C-589T IL-4 gene promoter in asthma patients was higher than
      for normal subjects (P < 0.0001). The frequency discrepancy was found to be even
      higher for asthmatic patients with severe AHR (P < 0.05). There were no
      significant differences for the T allele frequency among asthmatic patients with
      the various other phenotypes such as high versus normal total eosinophil, high
      versus normal total IgE and high versus normal levels of specific IgE against
      mite, cockroach or cat dander, or dog dander. CONCLUSIONS: Polymorphism in the
      promoter of the IL-4 gene is associated with asthma and is a disease modifier in
      terms of the severity of AHR.

PMID- 17207025
TI  - Lack of association between the microsatellite polymorphism in intron 2 of human
      Toll-like receptor 2 gene and bronchiectasis among Koreans.
AB  - BACKGROUND AND OBJECTIVE: The genetic factors for the development of
      bronchiectasis are not well understood in most patients. The aim of this study
      was to elucidate the possible association between bronchiectasis and guanine
      thymine (GT) repeat polymorphism in intron 2 of the human Toll-like receptor 2
      (TLR2), which has a crucial role in adaptive as well as innate immunity. METHODS:
      A total of 194 patients with bronchiectasis and the same number of age- and
      gender-matched healthy blood donors were prospectively enrolled. The numbers of
      GT repeats were determined by PCR and gene scans. For further analysis, the
      alleles were classified into three subclasses: 12-16 GT repeats, short alleles (S
      allele); 17-22 repeats, medium-length alleles (M allele); and 23-27 repeats, long
      alleles (L allele). RESULTS: The overall distribution of alleles was not
      different between patient and control groups (P = 0.71). In addition, the
      frequencies of genotypes including short alleles were not different between
      patient and control groups (P = 0.92). Extent of bronchiectasis (P = 0.92) and
      bacterial colonization (P = 0.48) were not associated with any subclass genotype.
      CONCLUSIONS: Alleles and genotype including the shorter GT repeats in intron 2 of
      the TLR2, were not associated with the development, extent and bacterial
      colonization of bronchiectasis in Koreans.

PMID- 17207026
TI  - Monoclonal antibody 7F9 recognizes rat protein homologous to human
      carboxypeptidase-M in developing and adult rat lung.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to obtain an antibody
      that would be useful for investigating the yet unclear molecular mechanism
      underlying the differentiation of lung alveolar type I and II cells. METHODS:
      Monoclonal antibodies were raised against membrane proteins from embryonal day
      18.5 rat lungs and characterized by immunoblotting on rat lung lysates at various
      developmental stages to select an appropriate clone. The antigen of the selected
      antibody was purified by serial column chromatography and immunoprecipitation and
      identified by mass spectrometry. RESULTS: 7F9 antibody recognizes a 65-kDa
      protein that is expressed most prominently from embryonal day 20.5 to postnatal
      day 1. This protein was identified as a rat protein that is similar to
      5730456K23Rik protein. The protein is homologous to human carboxypeptidase-M.
      Although human carboxypeptidase-M is known as a marker of type I cells, the
      expression of this rat protein was detected in columnar epithelial cells
      expressing type II cell markers, SP-C and a lamellar body protein ABCA3, in
      developing lung. Its expression was detected in alveolar cells lacking T1alpha, a
      type I cell marker protein, in adult lung. It was also expressed in RLE-6TN cells
      derived from type II cells. The expression in RLE-6TN cells was down-regulated by
      transforming growth factor-beta1 and up-regulated by Wnt3a. CONCLUSIONS: 7F9
      antibody detects a protein in rat lung cells expressing type II markers. The
      antibody is a useful tool for studying signalling triggered by transforming
      growth factor-beta1 and Wnt3a in rat type II cells.

PMID- 17207027
TI  - Oxidative stress and lipid-derived inflammatory mediators during acute
      exacerbations of cystic fibrosis.
AB  - BACKGROUND AND OBJECTIVE: In cystic fibrosis (CF) very few studies have assessed
      sputum 8-iso-PGF2alpha levels during pulmonary exacerbations as a direct measure
      of airway oxidative stress. The role of other lipid-derived inflammatory
      mediators, such as the cysteinyl leukotrienes (cys-LTs) and prostaglandin (PG)
      E2, during exacerbations is also poorly defined and the effect of conventional
      antibiotic therapy on these components of the inflammatory process is unclear.
      METHODS: Sputum 8-iso-PGF2alpha, total cys-LT and PGE2 levels were measured in 17
      CF patients experiencing a pulmonary exacerbation and repeated analysis were
      performed in 15 of these patients after antibiotic treatment. Eight stable CF and
      nine healthy subjects provided control data. RESULTS: Sputum 8-iso-PGF2alpha was
      significantly elevated in acute, but not stable CF patients versus healthy
      controls (P < 0.001). Similarly, sputum cys-LT and PGE2 levels were increased in
      acute compared with stable CF patients and healthy controls (P <or= 0.001).
      Although substantially lower than in acute patients, sputum cys-LT levels in
      stable patients were also significantly higher than in normal controls (P =
      0.01). There were strong associations between cys-LT levels and sputum total cell
      counts, and blood neutrophils in acute patients (r2 = 0.53, P = 0.001 and r2 =
      0.33, P < 0.05, respectively). Overall in the CF patients, FEV1% predicted was
      strongly and negatively correlated with sputum 8-iso-PGF2alpha (r2 = 0.34, P =
      0.006), cys-LT (r2 = 0.40, P = 0.002) and PGE2 (r2 = 0.52, P < 0.001) levels.
      Antibiotic treatment reduced sputum total cell count (P = 0.03), but did not
      affect 8-iso-PGF2alpha, cys-LT or PGE2 levels. CONCLUSIONS: CF exacerbations are
      characterized by increased oxidative stress and sputum concentrations of
      bioactive lipid mediators. Treatment does not modulate these aspects of
      inflammation and more targeted therapy needs further study.

PMID- 17207028
TI  - Efficacy of azithromycin administration in prevention of respiratory tract
      infection after bronchoscopic biopsy: a randomized, controlled trial.
AB  - BACKGROUND AND OBJECTIVE: Respiratory tract infection is a serious complication
      associated with bronchoscopic biopsy. This study attempted to examine its
      incidence and determine an efficacious therapy for preventing such infections.
      METHODS: Nine hundred and thirty patients who underwent bronchoscopic biopsy in
      Osaka City University Hospital outpatient clinic were enrolled in the study. All
      patients were randomly assigned to receive a 3-day course of azithromycin (500
      mg/day), cefcapene pivoxil hydrochloride (300 mg/day) or no antibiotics. The
      primary outcome was the incidence of respiratory tract infection after
      bronchoscopic biopsy among the three groups. RESULTS: In the no-treatment group,
      nine of the 310 patients (2.9%) had respiratory tract infection after
      bronchoscopic biopsy. All patients with infection had abnormal bronchoscopic
      findings. Of the patients with respiratory tract infection, 60% were in the no
      treatment group, 26.7% in the cefcapene group and 13.3% in the azithromycin
      group. Although not statistically significant, the incidence in the azithromycin
      group (0.7%) was lower than in the no-treatment group (P = 0.06). Among the
      patients with abnormal bronchoscopic findings, the incidence in the azithromycin
      group was significantly lower than that in the no-treatment group (3.0% vs.
      14.8%; P = 0.02). Moreover, maximum C-reactive protein values also appeared to be
      lower in the azithromycin group than in the no-treatment group and the cefcapene
      group. CONCLUSIONS: A 3-day course of azithromycin administration is well
      tolerated and effective in preventing infection post bronchoscopy.

PMID- 17207029
TI  - Effect of inhaled budesonide on oropharyngeal, Gram-negative bacilli colonization
      in asthma patients.
AB  - BACKGROUND AND OBJECTIVE: The effect of inhaled budesonide on oropharyngeal Gram
      negative bacilli colonization (OGNBC) in asthmatic patients was investigated.
      METHODS: Oropharyngeal cultures were obtained from asthmatic patients attending
      the hospital respiratory outpatient clinic, at baseline and 1 month after
      treatment with 800 microg/day of inhaled budesonide. Cultures were evaluated for
      OGNBC and compared with those of healthy controls. RESULTS: A total of 148
      cultures (74 from asthma patients, 74 from healthy controls) were evaluated. Six
      cultures (8.1%) from healthy controls, eight cultures (10.8%) from asthma
      patients obtained before treatment and 20 cultures (27.0%) obtained after
      treatment were positive for OGNBC (P < 0.05). Gender, age, presence of atopy and
      the degree of illness were not found to be related to the presence of OGNBC in
      and healthy control cultures. In the cultures obtained from the patients after
      treatment, OGNBC was higher in patients >50 years and in those with FEV1 < 70% (P
      < 0.05). Nine (18.8%) of 48 patients <50 years compare with 11 (42.3%) of the 26
      patients >50 revealed OGNBC (P < 0.05). OGNBC were observed in 18.9% of the
      patients with FEV1 = 70% and in 47.6% of those with FEV1 < 70% (P < 0.05).
      CONCLUSIONS: The increased rate of OGNBC in asthma patients treated with inhaled
      budesonide was found to be related to increased age and lower level of FEV1.
      Further studies with larger numbers of patients are required for the
      interpretation of this colonization in the course of lower respiratory infections
      in these patients.

PMID- 17207030
TI  - Sputum bacteriology in hospitalized patients with acute exacerbation of chronic
      obstructive pulmonary disease in Taiwan with an emphasis on Klebsiella pneumoniae
      and Pseudomonas aeruginosa.
AB  - BACKGROUND AND OBJECTIVE: Bacterial infection is one of the major causes of acute
      exacerbation of COPD (AECOPD). This study was undertaken to investigate the
      microbiology of AECOPD. METHODS: Medical records from 494 episodes of AECOPD in
      patients admitted to the National Taiwan University Hospital from January 2000 to
      June 2004 were reviewed. Severity of COPD was classified according to the 2003
      Global Initiative for Chronic Obstructive Lung Disease guideline. RESULTS:
      Potential pathogenic microorganisms were isolated from patients in 328 (66.4%)
      episodes of AECOPD. The predominant bacteria were Klebsiella pneumoniae (19.6%),
      Pseudomonas aeruginosa (16.8%) and Haemophilus influenzae (7.5%), followed by
      Acinetobacter baumannii (6.9%), Enterobacter species (6.1%) and Staphylococcus
      aureus (6.1%). The incidence of Streptococcus pneumoniae was 2.4%. Spirometry
      results obtained within 1 year of the exacerbation were available in 186 cases.
      K. pneumoniae was more frequently isolated in stage I COPD (39.1%) than stage II
      (16.6%), III (13.8%) and IV (9.4%). No glucose non-fermentative Gram-negative
      bacilli were isolated in stage I patients. Multivariate logistic regression
      analysis revealed that P. aeruginosa (odds ratio (OR) 3.19; 95% confidence
      interval (CI): 1.21-8.38), intubation (OR 14.81; 95% CI: 5.08-43.12) and age (OR
      1.1; 95% CI: 1.03-1.17) were independent risk factors for mortality. CONCLUSIONS:
      Klebsiella pneumoniae and P. aeruginosa are the most common sputum pathogens in
      hospitalized patients with AECOPD in Taiwan, with the former being more commonly
      isolated from mild COPD and the latter associated with poor clinical outcome.
      These results should be considered when deciding which antibiotics should
      initially be used to treat patients with AECOPD.

PMID- 17207031
TI  - Use of QuantiFERON-TB Gold to investigate tuberculosis contacts in a high school.
AB  - BACKGROUND AND OBJECTIVE: QuantiFERON-TB Gold (QFT-G) was employed in a contact
      investigation in a high school to evaluate its performance in adolescents.
      METHODS: Students of the same school grade as the index case were screened with
      tuberculin skin test (TST) and CXR examination as an initial contact
      investigation. QFT-G was performed for students demonstrating a positive TST
      (erythema larger than 30 mm). RESULTS: Of 349 students whose TST was completed,
      95 had positive TST responses, although the distribution of TST responses was
      similar for both high and low exposure groups. In contrast, only four of the 88
      TST-positive students tested with QFT-G were positive by this test, and three of
      these were from the high exposure group. Chemoprophylaxis was provided to only
      those four QFT-G-positive students. Follow up of the 91 students who were TST
      positive, but QFT-G-negative (or not tested), for more than 3.5 years revealed
      that none have developed active tuberculosis. CONCLUSIONS: QFT-G appears more
      specific than TST as contacts with positive TST and negative QFT-G responses were
      not offered prophylaxis and none developed tuberculosis during 3.5 years of
      follow up. The replacement of TST with QFT-G, or perhaps combined use of TST and
      QFT-G, may be more useful in diagnosing true infection and thus reducing the
      number of subjects indicated for chemoprophylaxis.

PMID- 17207032
TI  - Effects of bronchodilators on dynamic hyperinflation following hyperventilation
      in patients with COPD.
AB  - BACKGROUND AND OBJECTIVE: The present study was performed to examine the
      occurrence of dynamic hyperinflation following hyperventilation in COPD patients
      and former smokers without COPD, and the efficacy of short-acting anticholinergic
      agents (SAAC) and beta2-agonists (SABA) for lung hyperinflation following
      metronome-paced hyperventilation in COPD. METHODS: Fifty-nine patients with COPD,
      20 ex-smokers without COPD and 20 healthy subjects who had never smoked were
      examined for dynamic hyperinflation by metronome-paced hyperventilation with
      respiratory rate increasing from 20 to 30 and 40 tidal breaths/min. Dynamic
      hyperinflation was evaluated as the decrease in inspiratory capacity (IC)
      following hyperventilation, and the effects of SAAC and SABA on dynamic
      hyperinflation were assessed. RESULTS: COPD patients showed a significant
      increase in end-expiratory lung volume and a decrease in IC following
      hyperventilation, and ex-smokers without COPD also showed mild but significant
      dynamic hyperinflation. Multiple stepwise linear regression analysis revealed
      that the carbon monoxide transfer coefficient (DLco/VA) and RV/TLC were
      significant and independent determinants of dynamic hyperinflation in COPD.
      Treatment with SAAC and SABA significantly increased IC at each respiratory rate,
      independently of the increases in FEV1. Furthermore, SABA significantly inhibited
      the decrease in IC due to hyperventilation. CONCLUSIONS: These findings suggest
      that lung hyperinflation following hyperventilation may be a useful method for
      detecting dynamic hyperinflation observed not only in patients with COPD but also
      in ex-smokers without COPD, and both SAAC and SABA are effective in reducing
      dynamic hyperinflation in COPD.

PMID- 17207033
TI  - Influenza and rhinovirus infections among health-care workers.
AB  - BACKGROUND AND OBJECTIVE: Health-care workers (HCWs) are at higher risk of
      acquisition and transmission of respiratory virus infections. Nosocomial
      transmission of influenza has been documented but whether this is so for other
      respiratory viruses has not been assessed. METHODS: Epidemiological, clinical and
      viral laboratory surveillance was carried out on HCWs presenting with acute
      respiratory infection in a university hospital. RESULTS: Over a 2-year period,
      203 subjects were recruited: rhinovirus was the most frequently detected virus
      (37.7% in flu negative samples) and influenza A/B was positive in only 12.3% of
      subjects. Only 19.7% of HCWs were immunized against influenza. High detection of
      rhinovirus occurred even during the peak of the influenza season and half of the
      infected subjects reported an influenza-like illness. CONCLUSION: Rhinovirus
      infection occurred frequently in this study population and probably contributes
      to influenza misdiagnosis. Educational interventions about different viruses
      causing respiratory symptoms and an increase in standards of infection control
      besides influenza immunization among HCWs is needed.

PMID- 17207034
TI  - Clinical differentiation of atypical pneumonia using Japanese guidelines.
AB  - BACKGROUND AND OBJECTIVE: Atypical pneumonia occupies an important position in
      community-acquired pneumonia. The aim of this study was to examine whether making
      a diagnosis of atypical pneumonia is possible based upon the Japanese Respiratory
      Society guidelines. METHODS: The data from three prospective studies were
      reviewed. A total of 285 patients with mycoplasmal pneumonia or chlamydial
      pneumonia and 515 patients with pneumococcal pneumonia or Haemophilus influenzae
      pneumonia were assessed to determine whether these pneumonias met the diagnostic
      criteria for atypical pneumonia used in the Japanese Respiratory Society
      guidelines. The criteria were: (i) age less than 60 years; (ii) no or only minor
      underlying diseases; (iii) persistent cough; (iv) limited chest auscultatory
      findings; (v) no sputum, or no identified aetiological agent by rapid diagnosis;
      and (vi) a peripheral white blood cell count below 10,000/microL. RESULTS: All
      items of the criteria proved to be valid except for 'age' in patients with
      Chlamydophila pneumoniae pneumonia using multiple regression analysis. The
      sensitivity and specificity for atypical pneumonia were 77.0% and 93.0% based on
      four or more of the criteria respectively. CONCLUSION: Pure atypical pneumonia
      can be differentiated to some degree by clinical symptoms and laboratory
      findings. It is important to differentiate and treat bacterial pneumonia and
      atypical pneumonia in regions such as Japan, where Streptococcus pneumoniae
      resistance to macrolides is high. Treatment covering the two types of pneumonia
      should be considered in elderly patients and those with underlying respiratory
      disease.

PMID- 17207035
TI  - Early switch to oral antibiotics and early discharge guidelines in the management
      of community-acquired pneumonia.
AB  - BACKGROUND AND OBJECTIVE: The major cost of managing community-acquired pneumonia
      (CAP) relates to the duration i.v. antibiotic use and length of hospital stay
      (LOS). Guidelines on early switch to oral antibiotics and early discharge from
      hospital may help to achieve a unified approach to managing CAP. The aim of this
      study was to assess the benefits and safety of these guidelines in an Australian
      respiratory medicine unit. METHODS: This prospective study included consecutive
      patients admitted with a diagnosis of CAP over a 6-month period. Early switch to
      oral antibiotics and early discharge guidelines were implemented one month prior
      to the evaluation period. Comparison was made to a retrospective control group
      admitted before the guidelines were implemented. Data collection included patient
      demographics, clinical and outcome parameters, duration of i.v. antibiotics and
      LOS. Thirty-day outcomes on patient safety and satisfaction were collected from
      the prospective group. RESULTS: One hundred and twenty-five patients in the
      prospective group were compared to 100 patients in the controls. Baseline
      characteristics were similar between the comparison groups. Both the mean
      duration of i.v. antibiotics used (3.38 +/- 0.22 vs. 3.99 +/- 0.28 days, P =
      0.03) and LOS (7.62 +/- 0.60 vs. 8.36 +/- 0.55 days, P = 0.04) were significantly
      shorter in the prospective group. Thirty-day readmission rate was 6% and patient
      self-reported overall satisfaction was 93.9% in those who were followed up.
      CONCLUSIONS: The use of early switch and early discharge guidelines for CAP
      reduced the duration of i.v. antibiotics and LOS while maintaining high levels of
      safety and patient satisfaction.

PMID- 17207036
TI  - Open-label, randomized comparison trial of long-term outcomes of levofloxacin
      versus standard antibiotic therapy in acute exacerbations of chronic obstructive
      pulmonary disease.
AB  - BACKGROUND AND OBJECTIVE: This study investigated whether treating acute
      exacerbations of COPD (AE-COPD) with levofloxacin modifies the long-term outcome
      of COPD patients in comparison with standard antibiotic regimens. METHODS: A 6
      month open-label clinical trial of AE-COPD patients compared the outcomes of
      treating with levofloxacin versus standard therapy (clarithromycin, cefuroxime,
      or amoxicillin/clavulanate) at recommended doses for 10 days. Several variables
      were analysed: pulse oximetry, FEV1, health-related quality of life, infection
      free interval, number of exacerbations, hospitalizations due to an exacerbation
      and mortality. RESULTS: Of the 116 patients initially enrolled, completion or
      withdrawal information was available for 50 patients in the levofloxacin arm and
      52 in the standard therapy arm. At the end of the study, there were no
      differences in mortality (17.8% vs. 22.9%, P = 0.53), number of exacerbations (33
      vs. 41, P = 0.40), pulse oximetry (median 91.71% vs. 92.46%, P = 0.18), FEV1
      (median 51.31% vs. 47.14%, P = 0.30), health-related quality of life (median 8.63
      vs. 10.75, P = 0.94) and infection-free interval (median 112 vs. 101 days, P =
      0.72), for the levofloxacin and standard therapy, respectively. However, 12 out
      of 33 (33.6%) exacerbations treated with levofloxacin required in-hospital
      management versus 27 out of 41 (65.8%) treated with standard therapy (P = 0.02).
      CONCLUSION: This preliminary study suggests that 10-day treatment of AE-COPD with
      levofloxacin is associated with a reduction in hospitalizations compared with
      standard antibiotics despite there being no significant benefit in other outcome
      variables.

PMID- 17207037
TI  - Prevalence of symptomatic large pleural effusions first diagnosed more than 30
      days after coronary artery bypass graft surgery.
AB  - BACKGROUND AND OBJECTIVE: Symptomatic large pleural effusions (>25% of
      hemithorax) are sometimes diagnosed after coronary artery bypass graft surgery
      (CABG). Their incidence and outcome have not been fully described. This study
      aims to discuss the prevalence and the clinical course in patients diagnosed with
      symptomatic newly developed large pleural effusions at least 30 days after CABG.
      METHODS: A retrospective study of 410 patients who underwent CABG over a three
      and a half year period was undertaken. The type of surgery, timing of occurrence
      of effusion after CABG, amount and characteristics of the pleural effusion, left
      ventricular dimension and ejection fraction were obtained from medical records
      and cardiac surgery databases. RESULTS: The records of 356 patients 1 month post
      CABG were available for evaluation. The initial diagnosis of a newly developed
      symptomatic large pleural effusions was made in 11 patients (3.1%) at least 30
      days after CABG. Eight had a pleural effusion predominantly on the left side and
      three on the right. Patients were further divided into two groups: those who had
      effusions diagnosed between 30 and 90 days post CABG (group 1) and those
      diagnosed more than 90 days post-CABG (group 2). The pleural fluid LDH levels
      were higher in patients in group 1 (1262.0 +/- 921.3 U/L vs. 117.5 +/- 35.1 U/L,
      P = 0.02). Patients in group 2 had evidence of cardiac impairment compared with
      those in group 1, as evidenced by a lower ejection fraction (68.8 +/- 6.0% vs.
      52.0 +/- 10.6% in groups 1 and 2, respectively, P = 0.01) and higher left
      ventricular end-diastolic dimension (45.2 +/- 6.0 mm vs. 55.3 +/- 8.4 mm in
      groups 1 and 2, respectively, P = 0.05). CONCLUSIONS: The incidence of
      symptomatic newly developed large pleural effusions first diagnosed at more than
      30 days post CABG was 3.1%. Those who were diagnosed between 30 and 90 days post
      CABG tended to have exudative effusions, whereas those diagnosed more than 90
      days post CABG often had left ventricular impairment and transudative effusions.
      Most of these effusions settled with conservative management and did not recur.

PMID- 17207038
TI  - Using discrete choice experiments to investigate subject preferences for
      preventive asthma medication.
AB  - BACKGROUND AND OBJECTIVE: Long-term adherence to inhaled corticosteroids is poor
      despite the crucial role of preventer medications in achieving good asthma
      outcomes. This study was undertaken to explore patient preferences in relation to
      their current inhaled corticosteroid medication, a hypothetical preventer or no
      medication. METHODS: A discrete choice experiment was conducted in 57 adults with
      mild-moderate asthma and airway hyper-responsiveness, who were using inhaled
      corticosteroid <or=500 microg/day (beclomethasone equivalent). In the discrete
      choice experiment, subjects evaluated 16 hypothetical scenarios made up of 10
      attributes that described the process and outcomes of taking asthma medication,
      with two to four levels for each attribute. For each scenario, subjects chose
      between the hypothetical medication, the medication they were currently taking
      and no asthma medication. A random parameter multinomial logit model was
      estimated to quantify subject preferences for the aspects of taking asthma
      medication and the influence of attributes on medication decisions. RESULTS:
      Subjects consistently made choices in favour of being able to do strenuous and
      sporting activities with or without reliever, experiencing no side-effects and
      never having to monitor their peak flow. Frequency of collecting prescriptions,
      frequency of taking the medication, its route of administration and the strength
      of the doctor recommendation about the medication were not significant
      determinants of choice. CONCLUSIONS: The results of this study suggest that
      patients prefer a preventer that confers capacity to maximize physical activity,
      has no side-effects and does not require daily peak flow monitoring.

PMID- 17207039
TI  - Serum progastrin-releasing peptide levels followed by whole-body positron
      emission tomography detects early recurrence of small-cell lung cancer.
AB  - A 65-year-old male smoker with severe COPD was diagnosed with limited-stage small
      cell lung cancer. After receiving cisplatin/irinotecan, serum progastrin
      releasing peptide (ProGRP) levels decreased to within the reference values and
      the lesions were markedly reduced in size. A whole-body 18F-fluorodeoxyglucose
      PET (FDG-PET) scan confirmed complete remission. During follow up, serum ProGRP
      levels increased, and a whole-body FDG-PET scan detected recurrence at the hilar
      lymph node that had been negative on CT. Complete remission was again achieved
      with second-line chemotherapy (cisplatin/etoposide) and local irradiation to the
      hilar lymph node. Monitoring serum ProGRP levels, followed by whole-body FDG-PET
      when indicated, may improve the clinical management of patients with small-cell
      lung cancer after initial complete remission.

PMID- 17207041
TI  - Thymic and pulmonary mucosa-associated lymphoid tissue lymphomas in a patient
      with Sjogren's syndrome and literature review.
AB  - Mucosa-associated lymphoid tissue lymphoma (MALToma) has been reported in several
      organs. Among MALTomas, thymic and pulmonary MALTomas are rare. The present
      report describes a patient with Sjogren's syndrome who presented thymic and
      pulmonary MALTomas. Although the exact pathogenetic relationship between these
      two tumours is uncertain, it is likely that the underlying immune dysregulation
      related to Sjogren's syndrome contributed to the occurrence and the unusual
      manifestation of MALTomas in this patient.

PMID- 17207040
TI  - Increase in soluble CD138 in bronchoalveolar lavage fluid of multicentric
      Castleman's disease.
AB  - Multicentric Castleman's disease (MCD) is a rare and often incurable
      lymphoproliferative disorder. It is typically a systemic illness, but
      occasionally manifests primarily as a pulmonary parenchymal disease with massive
      infiltration of CD138 (syndecan-1)-positive plasma cells. This is the first
      report to demonstrate a marked elevation of soluble CD138, despite the absence of
      plasma cells, in BAL fluid in an MCD patient with pulmonary involvement. This
      finding suggests that the quantitative measurement of soluble CD138 in BAL fluid
      may reflect plasma cell infiltration and disease activity in the lungs of
      patients with MCD.

PMID- 17207042
TI  - Delayed presentation of amniotic fluid embolism: lessons from a case diagnosed at
      autopsy.
AB  - Amniotic fluid embolism (AFE) syndrome, a catastrophic cause of respiratory
      failure typically occurs during labour, or soon after delivery. Systemic
      hypotension is the most prominent haemodynamic alteration documented in patients
      with AFE, a consequence principally of severe left-sided heart failure. A 22-year
      old female was admitted to the respiratory intensive care unit with severe
      eclampsia and acute respiratory failure 4 h following delivery. Her blood
      pressure was elevated (systolic 150-180 mm Hg, diastolic 90-110 mm Hg) throughout
      the admission. She succumbed in spite of therapy for eclampsia and mechanical
      ventilation. Autopsy revealed large numbers of polygonal, anucleate foetal
      squames and mucin in the pulmonary vasculature typical of AFE while changes of
      eclampsia were found in the liver and kidneys. It appears that AFE syndrome can
      have a delayed presentation, as late as 4 h after delivery and haemodynamic
      collapse may not be mandatory if the patient has coexisting systemic hypertension
      secondary to severe eclampsia.

PMID- 17207043
TI  - Value of recommended spirometer accuracy checks on office spirometers in primary
      care unknown.

PMID- 17207046
TI  - Crocodiles and neonatal resuscitation.

PMID- 17207047
TI  - Growth charts for use in Australia.
AB  - Growth charts for use in Australia have recently been modified. Changes have been
      made to both height for age and weight for age charts as well as body mass index
      for age. The charts are now based on the published CDC 2000 growth data which are
      more contemporary than the data used to construct the previous charts. A first
      centile for height for age has been included as this is used as a screening tool
      for the provision of growth hormone to children in Australia. The calculation of
      a precise first centile has been possible as the CDC data includes LMS values
      which have other significant advantages in the creation of the growth charts. It
      is noteworthy that the most recently collected anthropometric data for weight
      (and hence body mass index) have not been included in the calculation of these
      two charts as it was believed that increasing numbers of children who are
      overweight or obese in the population would skew these charts in an undesirable
      way. Height velocity for age and other charts remain unchanged.

PMID- 17207048
TI  - New Australian Neonatal Resuscitation Guidelines.
AB  - New Australian Neonatal Resuscitation Guidelines highlight the recent advances in
      neonatal resuscitation. Resuscitation should start with air and only use oxygen
      if the infant does not respond. CPAP and PEEP should be considered for premature
      infants with meconium stained liquor. Sucking out the mouth and nose is not
      necessary. Infants less than 28 weeks gestation should be placed in a
      polyethylene bag or wrap to keep warm. Chest compressions, when required, remain
      at 3:1 inflation. The endotracheal tube position must be verified with a carbon
      dioxide detector.

PMID- 17207049
TI  - Management of the newborn infant affected by maternal opiates and other drugs of
      dependency.
AB  - Illicit drug use during pregnancy is common and probably underestimated in the
      majority of published studies. The infant exposed to opiates or other drugs of
      dependency during intrauterine development is at risk for post-natal withdrawal
      as well as to long-term problems that are associated with drug-effects and often,
      adverse social circumstances. This article examines the early management of the
      infant and mother for detection and monitoring of drug-exposure, pharmacological
      intervention for withdrawal and the management of associated, particularly
      infective and psychosocial, problems. Practical concerns surrounding these issues
      are discussed and further research on psychosocial intervention to improve long
      term outcome are much needed.

PMID- 17207050
TI  - Drug therapy for attention-deficit/hyperactivity disorder-like symptoms in
      autistic disorder.
AB  - Problems of inattention and hyperactivity affect one half of individuals with
      autistic disorder. Care must be taken to ensure that inattention and
      hyperactivity are not manifestations of other behavioural pathology seen in
      association with autistic disorder, as this will affect treatment decisions. The
      prescribing of psychotropic agents to individuals with autistic disorder is
      increasing but the evidence base is limited, with some exceptions, to
      uncontrolled studies. Substantial benefit in reducing inattention and
      hyperactivity is seen with atypical antipsychotics such as risperidone and
      quetiapine, although weight gain and sedation are common side effects. Moderate
      benefit is derived from methylphenidate, atomoxetine, some anticonvulsant
      medications, guanfacine and donepezil. Data show dexamphetamine, clonidine,
      clomipramine, mirtazapine, and fluoxetine are of unlikely benefit.

PMID- 17207051
TI  - Neonatal presentations to a Mixed Emergency Department.
AB  - AIMS: To investigate the characteristics of neonates presenting to a metropolitan
      Mixed Emergency Department (MED). To examine whether there are maternal and
      neonatal characteristics which increase the risk of presentation to the ED in the
      neonatal period. METHODS: A retrospective chart review was performed of all
      neonatal presentations occurring between July 2002 and June 2003 to Liverpool
      Hospital Emergency Department, a Level 6 MED located in south-western Sydney, New
      South Wales, Australia, seeing approximately 45,000 presentations annually of
      which 20% are paediatric. Comparisons of maternal and neonatal characteristics
      were made with Liverpool Hospital, Area Health Service and New South Wales
      Mothers and Babies data, and with other paediatric presentations to the MED.
      RESULTS: 179 neonates made 194 neonatal presentations. Compared with all
      paediatric presentations, the neonatal triage category assignment, admission and
      transfer proportions were significantly higher, although just over half had
      'primary care type illnesses'. Mothers of neonates presenting to this MED were
      more likely to be younger and first time mothers in comparison to the general
      population of mothers and newborns. This study did not find an over
      representation of neonates who were discharged within 48 h after birth.
      CONCLUSION: The implications of these results for practice include a
      consideration of the availability and appropriateness of after-hours service
      available to new mothers. Further studies investigating parental reasons for
      neonatal ED presentation are recommended.

PMID- 17207052
TI  - Respiratory syncytial virus infection and recurrent wheeze/asthma in children
      under five years: an epidemiological survey.
AB  - AIM: To determine the rates of respiratory syncytial virus (RSV) infection in
      children under 5 years of age with recurrent wheeze or asthma and compare their
      clinical presentation, course and outcome with asthmatic children of the same age
      who did not have RSV. METHODS: Children were recruited prospectively from the
      emergency department of the Royal Children's Hospital, Melbourne during peak RSV
      season in 1998. Information was collected regarding past and current asthma
      presentations, a nasopharyngeal asprirate was taken for viral isolation and all
      children were reviewed by telephone 1 week following presentation. RESULTS: 73
      children were included with a median age of 28 months. RSV was isolated from 33
      (45%) of children, one child had adenovirus and in the remainder no virus was
      isolated. Children less than 12 months were more likely to have RSV (70%). RSV
      positive children had a longer duration of illness prior to hospital presentation
      than RSV-negative children but were not more likely to be admitted or to have a
      longer duration of ongoing symptoms. CONCLUSION: A high rate of RSV infection was
      demonstrated in young children with recurrent wheeze or asthma during the RSV
      season. This information has important implications for the control of nosocomial
      infection with RSV (i.e. isolation of patients) and in targeting another group to
      be included for RSV vaccine development.

PMID- 17207053
TI  - Role of the tertiary child protection paediatrician: expert and advocate.
AB  - AIM: The role of the child protection paediatrician is varied. This study
      examines perceptions of how tertiary child protection (tCP) paediatricians view
      their multifaceted roles, perceived adequacy of length of pre-FRACP training and
      how this relates to confidence and satisfaction in their roles. METHODS: An
      anonymous self-report survey was distributed to child protection paediatricians
      working in tertiary hospitals across New Zealand and Australia. The survey
      addressed the adequacy of training and confidence within the diverse roles
      encountered within child protection work. It also identified perceptions of
      stress and satisfaction. RESULTS: Responses were received from 32 out of 45 of
      eligible tCP paediatricians (72%). The majority (71.8%) had entered directly into
      a tCP unit in their first consultant position. Two-thirds (65.7%) of tCP
      paediatricians received less than 4 months of pre-FRACP child protection training
      while a third received no training at all. Generally tCP paediatricians perceived
      their training in all domains of child protection to be inadequate although their
      current confidence levels in all roles are high. They expressed most concerns
      within their role as forensic expert. CONCLUSION: Despite receiving little or no
      training pre-FRACP in child protection, this group of tCP paediatricians function
      in their specialised roles in tCP and feel confident in fulfilling the dimensions
      of forensic expert and child advocate. As the field of medical child protection
      continues to evolve, it is important for training to keep pace with expectations
      of the varied roles of the paediatric specialist in child protection.

PMID- 17207054
TI  - Total steroid dose given to ventilated newborn infants with chronic lung disease.
AB  - AIM: There are currently two dexamethasone regimes used in our nursery. We aimed
      to retrospectively compare the cumulative dose of dexamethasone that infants on
      each regime received and the requirement for further courses. METHODS: Infants
      receiving dexamethasone between 1 January 2000 and 31 December 2004, with a
      gestational age of <30 weeks or a birthweight of <1000 g, were identified and
      then a chart review of these infants was undertaken. Demographic data were
      obtained and compared as was the total dose of dexamethasone and number of
      courses that each infant received. Some clinical outcome measurements were also
      obtained. RESULTS: A total of 119 infants were identified. The total
      dexamethasone dose received was 1.92 mg/kg less for infants commencing on the 2
      week course compared with the 6-week course (difference between medians, Mann
      Whitney test, P=0.005). Infants having the 2-week course had 17 days less steroid
      treatment (difference between medians, Mann-Whitney test, P=0.0001). Seventeen
      (46%) subjects who started on a 2-week course of steroids and 18 (22%) who
      started on a 6-week course required at least one further course of steroids
      (Fisher's exact test, P=0.01). There were no significant differences in the short
      term outcome measures of neonatal chronic lung disease. CONCLUSION: Infants who
      received the 2-week course of dexamethasone had a 27% reduction in total steroid
      dose compared with infants receiving a 6-week course with similar short-term
      outcomes. However, our study was limited by its retrospective nature and possible
      confounding factors.

PMID- 17207055
TI  - Chronic lung disease of prematurity and respiratory outcome at eight years of
      age.
AB  - AIM: The study aimed to determine the respiratory outcome of children who had
      chronic lung disease of prematurity (CLD) compared with a preterm control group
      of children at school age. METHODS: Fifty-two preterm infants with CLD born
      between 26 and 33 weeks gestation were assessed regarding respiratory illness
      with 47 having lung function testing. Information regarding respiratory illness
      was obtained from 52 children in the birthweight-matched control group of whom 45
      had lung function testing. The results were compared between the CLD and control
      groups. RESULTS: There was no difference in respiratory symptomatology between
      CLD groups and control preterm infants. On lung function testing, a significantly
      lower mean forced expiratory flow at 25-75% of vital capacity was identified
      compared with the preterm controls (P=0.024). This significant difference did not
      persist after bronchodilator therapy. There was no evidence of increased air
      trapping or bronchial hyper-reactivity in the CLD children compared with the
      controls. CONCLUSION: Lung function in CLD children is largely normal in
      comparison with preterm controls, apart from some evidence of reversible small
      airway obstruction. Respiratory symptomatology is not increased in chronic
      disease children in comparison with control preterm children.

PMID- 17207056
TI  - Probabilities of heart donors arising within specified times for child
      recipients.
AB  - AIM: To determine the availability of donor hearts for children of different
      blood group and weight needing urgent heart transplantation. METHODS: Data
      maintained by the Australia and New Zealand Organ Donor Registry 1989-2004 were
      analysed to determine the frequency of donation. Probabilities of suitable donor
      availability within 10, 20, 30, 40, 60, 90 and 180 days were estimated using a
      Poisson model with the assumptions that traditional ABO blood compatibilities
      applied, suitable donors were 0.8-4.0 times the recipient's body weight (BW) and
      suitable adult donors were aged <40 years. RESULTS: Probabilities of suitable
      donor availability increase with passage of time from 10 to 180 days and decrease
      with competition from other needful recipients. Maximum suitable donor
      availability occurs for children of all blood groups at body weight 20 kg. The
      probabilities of a donor heart arising within 40 days (maximum safe duration of
      extracorporeal membrane oxygenation support locally available for young children)
      for this recipient body weight according to blood group is 0.89, 0.85, 0.73, 0.67
      (AB, A, B, O). Probabilities for recipients of BW 3 kg and 60 kg respectively are
      0.16, 0.14, 0.10, 0.09 (AB, A, B, O) and 0.66, 0.61, 0.47, 0.42 (AB, A, B, O).
      CONCLUSION: Expectation of suitable heart donation arising within 40 days for
      needful recipients in Australia is low for infants (probability <0.3), moderate
      for small children (probability 0.5-0.9) and modest for large children
      (probability 0.4-0.7), with variation at all body weights according to blood
      group and waiting time.

PMID- 17207057
TI  - Retrospective analysis of patients attending a neurofibromatosis type 1 clinic.
AB  - AIM: To undertake a retrospective analysis of the patients who attended the
      neurofibromatosis type 1 clinic (NF clinic) at the Royal Children's Hospital,
      Melbourne between March 2001 and May 2004. From this analysis, we aimed to
      ascertain the frequency and nature of complications of NF1 in this cohort and
      compare this with other large series. METHODS: Genetic files and hospital records
      of patients who attended the NF clinic were reviewed. Data regarding the clinical
      features and NF1-related complications present in the patient population were
      entered into a database and then analysed. RESULTS: Data were available for 121
      patients with presumed or confirmed diagnoses of NF1 who attended the NF clinic
      between the study dates. While most patients were referred to the clinic for
      'routine surveillance', complications of NF1 were common. Forty-four per cent of
      patients had learning difficulties, 21% had optic gliomas and 17% had plexiform
      neurofibromas. Fifty-five per cent of those with plexiform neurofibromas required
      at least one surgical procedure. CONCLUSION: The NF clinic was accessed by
      patients of all ages to assist with diagnosis, provide routine surveillance and
      manage complex complications of NF1. The prevalence and range of complications of
      NF1 of the patients attending this clinic is similar to other large retrospective
      studies in tertiary centres.

PMID- 17207058
TI  - Functional time limit and onset of symptoms in infant abusive head trauma.
AB  - AIM: To analyse medical and witness evidence collected during investigations of
      infant abusive head trauma with a view to (i) isolating cases where a functional
      time limit could be established and (ii) examining those cases for evidence of
      the onset of neurological symptoms. METHODS: A retrospective study was undertaken
      of severe infant abusive head trauma cases investigated by the Queensland Police
      Service over a 10-year period. In cases where sufficient reliable (non
      perpetrator) evidence was available, a functional time limit was documented.
      Those files were then examined for further medical, witness or perpetrator
      evidence of the infant victim's response to the assault. RESULTS: A functional
      time limit was established in 16 of 52 cases (31%). In 11 of the 16 cases there
      was evidence of an immediate neurological response on the part of the victim.
      CONCLUSION: The study suggests that the period between assault and onset of
      symptoms in infant abusive head trauma is brief, particularly in cases of an
      acute deterioration where proximate medical intervention is required. In those
      cases with sufficient evidence of the victim's condition post-injury, the
      symptoms presented without delay.

PMID- 17207059
TI  - Sleep problems in young infants and maternal mental and physical health.
AB  - AIM: Sleep problems in the second 6 months of life are common and associated with
      maternal depression. This paper extends previous research to (i) establish the
      prevalence of sleep problems in younger infants from a broader socio-economic
      spectrum, (ii) examine the relationship between infant sleep problems and
      maternal physical, as well as mental, health, and (iii) explore mothers' sleep
      quality as a potential mediator of this relationship. METHODS:  DESIGN: Cross
      sectional, community survey in Melbourne, Australia. SAMPLE: Mothers of 3- to 6
      month-old infants (mean 4.6 months) recruited from well-child clinics in six
      sociodemographically diverse metropolitan local government areas. OUTCOME
      MEASURES: Maternal mental and physical health; standardised questionnaire on
      infant sleep patterns; maternal report of an infant sleep problem (yes/no).
      RESULTS: The survey was completed by 692 mothers; 237 (34%) reported an infant
      sleep problem, of whom 73 (31%) rated the problem as severe. Sleep patterns
      characterising a problem included the infant waking seven nights per week,
      nursing the infant to sleep at the beginning of the night, the infant sleeping in
      the parent's room, and parental disagreement regarding managing infant sleep.
      There was no relationship between sleep problems and socio-economic levels.
      Mothers reporting infant sleep problems had poorer mental and physical health
      compared with those not reporting sleep problems. CONCLUSION: Sleep problems are
      common in early infancy across metropolitan socio-economic levels and are
      associated with poorer maternal health and well-being. Preventive strategies for
      infant sleep problems need to begin early in primary care to improve mothers'
      health.

PMID- 17207060
TI  - Outcome and recurrence in treatment of phimosis using topical betamethasone in
      children in Hong Kong.
AB  - AIM: To study the efficacy of treating phimosis with topical steroid, and its
      long-term outcome and side effects. We also looked into the effect of daily
      retraction and cleansing of prepuce on preventing recurrence of phimsosis.
      METHODS: This prospective study comprised 138 boys who were prescribed 0.05%
      betamethasone ointment (Diprocel) during 1 August 2001-31 July 2004. Five boys
      were excluded because of non-compliance. Of the remaining 133 boys, 108 were
      followed-up and assessed. Age ranged from 0.03 to 12.9 years (mean=3.38,
      SD=2.79). The number of treatment course received, short-term and long-term
      outcome, side effects and the effect of daily foreskin retraction were studied.
      RESULTS: The success rate of first treatment course was 81.5%, and 60.2% of boys
      remained free from phimosis upon latest assessment. The follow-up period ranged
      from 0.4 to 4.4 years (mean=2.45, SD=0.90). There were no side effects noted. We
      found a significant and linear relationship between daily foreskin retraction and
      sustained resolution of phimosis. CONCLUSION: Topical steroid is an effective and
      safe treatment for phimosis, especially when combined with a good hygiene
      practice of the foreskin with daily cleansing and retraction. A trial of topical
      steroid treatment should be offered upon considering circumcision.

PMID- 17207061
TI  - Unusual haematologic manifestations of Mycoplasma pneumoniae infection.
AB  - A 2-year-old male presented with fever, cervical lymphadenopathy, anaemia,
      neutrophilia and thrombocytosis. There was no evidence of pulmonary disease.
      Severe cold antibody (IgM) mediated haemolytic anaemia developed during
      admission. Infection with Mycoplasma pneumoniae was demonstrated, highlighting
      the extrapulmonary manifestations of the infection, in the absence of pulmonary
      signs.

PMID- 17207062
TI  - Gallstone pancreatitis in a 6-month-old child.

PMID- 17207063
TI  - Spontaneous pneumoperitoneum after pneumonia in a child.
AB  - Pneumoperitoneum is considered to be a surgical emergency as it nearly always
      indicates a perforated abdominal viscus. However, in rare cases, the presence of
      'free gas under diaphragm' may not imply the need for emergent laparotomy, as
      pneumoperitoneum can occur without any gastrointestinal leakage. Here we report a
      rare case of a previously healthy boy with pneumoperitoneum associated with
      pneumonia and perform a review of the literature to explore the etiological
      mechanisms and the pathophysiology of non-surgical pneumoperitoneum.

PMID- 17207064
TI  - Successful treatment of cutaneous and subcutaneous zygomycosis in an
      immunosuppressed patient with aplastic anaemia.
AB  - Zygomycosis in patients with persistent neutropenia had been associated with poor
      outcomes despite aggressive surgical and antifungal therapy. We describe the case
      of a 10-year-old girl with aplastic anaemia and persistent neutropenia who
      developed cutaneous and subcutaneous zygomycosis of her right thigh that was
      successfully treated with extensive surgical debridement, intravenous liposomal
      amphotericin B, later changed to oral posaconazole for long-term suppressive
      therapy and granulocyte colony stimulating factor.

PMID- 17207065
TI  - Acute encephalopathy and rhabdomyolysis following rotavirus gastroenteritis.
AB  - Rotavirus is a common cause of severe gastroenteritis in children, and other
      unusual extraintestinal manifestations have also been attributed to the virus. We
      report a case of acute encephalopathy and rhabdomyolysis following rotavirus
      gastroenteritis in a 6-month-old infant.

PMID- 17207066
TI  - Moving forwards from the human genome project.

PMID- 17207067
TI  - Looking out for overweight/obesity in Australian pre-schoolers: who's actually
      doing it?

PMID- 17207068
TI  - Kawasaki disease: unusual manifestations and complications.

PMID- 17207072
TI  - Oral health status in war veterans with post-traumatic stress disorder.
AB  - The aim of this study was to assess the oral health condition of Croatian war
      veterans with post-traumatic stress disorder (PTSD). The study included 50 men
      who experienced combat stress and had been diagnosed with PTSD. They were
      compared with the group of 50 age-matched men who did not participate in war and
      did not have PTSD. Xerostomia, oral mucosal lesion, oral hygiene status, dental,
      and periodontal conditions, as well as temporomandibular disorders (TMDs) were
      assessed and compared between the groups. Subjects in PTSD group had poorer oral
      hygiene, and periodontal status compared with the control subjects. Furthermore,
      they had less teeth than the control group (P = 0.04). Although, there was no
      statistically significant difference between the groups in Decayed, Missing and
      Filled Teeth (DMFT) index (P = 0.36), PTSD group had more decayed and missing
      teeth, but less filled teeth (P < 0.05 for all). According the Research Diagnosis
      Criteria for Temporomandibular Disorder (RDC/TMD), PTSD patients had more TMD
      diagnoses compared with the control subjects. The most prevalent diagnosis was
      myofascial pain (48%) in PTSD group, while in the control group it was disc
      displacement with reduction (8%). It can be concluded that the oral health
      condition in PTSD patients is significantly affected compared with the control
      subjects.

PMID- 17207073
TI  - Influence of topical capsaicin on facial sensitivity in response to experimental
      pain.
AB  - Capsaicin, the pungent component of the red pepper, has been used as an analgesic
      in a variety of pain conditions, but sensory impairment after long-term treatment
      has been concerned. This study investigated the influence of topical capsaicin on
      various types of sensations including pain in the facial areas innervated by the
      mental nerve, and also evaluated whether the measurement of cutaneous current
      perception threshold (CPT) is reliable for the quantification of sensory change
      following capsaicin application. Twenty healthy subjects were given topical
      capsaicin cream (0.075%), which was applied to the mental area unilaterally, four
      times daily for 2 weeks. Burning sensation after capsaicin application gradually
      decreased with repeated applications. Repeated topical capsaicin resulted in
      reduced sensation to mechanical, heat and cold pain without changing non-painful
      tactile sensation. It also resulted in increased CPTs at 5 Hz and 250 Hz stimuli
      but no change in the CPTs at 2000 Hz from the first evaluation after capsaicin
      treatment and throughout the treatment period. This study demonstrated that
      topical capsaicin treatment for the management of chronic localized pain can be
      safely applied to the face without affecting non-painful normal sensations, and
      that CPT testing is a clinically useful tool for the quantification of sensory
      changes following capsaicin application.

PMID- 17207074
TI  - Changes in jaw muscle EMG activity and pain after third molar surgery.
AB  - Limited jaw-opening capacity is frequently encountered following third molar
      surgery and may impair function. The aim of this study was to investigate the
      electromyographic (EMG) activity in jaw muscles after third molar surgery to
      obtain more insight into the mechanisms of restrictions in jaw opening. Twenty
      subjects were examined before, 24 h and 1 week after surgery. Ten healthy
      controls were subjected to the same examination at two different occasions for
      intersession variability. The EMG activity of the masseter and anterior
      digastricus muscles was recorded at different jaw positions and during maximum
      voluntary clenching. Pain intensity was assessed at rest and during movements.
      The EMG activity in the jaw muscles increased with opening level (P < 0.01), but
      did not change after surgery. In contrast, the EMG activity during clenching was
      decreased in all muscles after surgery (P < 0.05). The pain intensity after
      surgery increased with jaw opening level (P < 0.001), but was in general not
      correlated to EMG level. Pain intensity during clenching was increased after
      surgery (P < 0.001), but not correlated to EMG level. The EMG activity did not
      change between visits in the control group. In conclusion, the results indicate
      that third molar surgery does not influence the EMG activity in the masseter and
      anterior digastricus muscles during various levels of static jaw opening, but
      decreases the EMG activity during clenching. However, these changes are not
      influenced by pain intensity. The results have implications for the understanding
      of the phenomenon of trismus.

PMID- 17207075
TI  - Changes in condylar path inclination during maximum protrusion between the ages
      of 6 and 12 years.
AB  - The purpose of this study is to quantify the changes in sagittal condylar path
      inclination during mandibular protrusion between the ages of 6 and 12 years. A
      total of 172 children (82 males and 90 females) ranging in age from 6.5 to 12.9
      years were divided according to their chronological age into five subgroups with
      mean ages of 7.1, 8, 9, 10 and 11.4 years respectively. The control group
      consisted of 41 adults with a mean age of 28 years. All subjects had a normal
      temporomandibular joint function and neutral occlusion. Five maximum protrusion
      retrusion movements were recorded with six degrees of freedom in each subject
      using an ultrasound (JMA) jaw-tracking system. Initially, condylar path
      inclination angle (CPIA) was calculated stepwise for each millimetre distance,
      for the first 10 mm of protrusive tracing path on both sides. A single mean value
      was then assigned for the entire protrusive path. One-way analysis of variance
      proved to be significant among the five subgroups of children. Linear regression
      analysis showed that condylar path had a tendency to become steeper with age,
      although it was statistically weak. The data indicated that the mean CPIA is 43
      degrees -44 degrees at the age of seven, increases annually by 1.2 degrees -1.3
      degrees and reaches an average of 49 degrees -50 degrees by the age of 12 at
      which time it attains around 83-85% of its adult level. In subgroup V, the female
      population had significantly steeper condylar path on the left-hand side than the
      male population. Condylar path inclinations indicated a symmetrical growth
      pattern of the articular eminence.

PMID- 17207076
TI  - Pivot appliances - is there a distractive effect on the temporomandibular joint?
AB  - The purpose of this study was to investigate the distractive effect of posterior
      occlusal pivots on the temporomandibular joint. The study comprised 23 healthy
      subjects. None of them had a third molar and none of them had a missing tooth or
      showed tooth mobility. All subjects clenched (i) on 1 mm tin foil positioned
      between the teeth 17/47 and 27/37; (ii) on a stiff bite registration material of
      1 mm thickness that prevented protrusion because of its bold occlusal relief.
      During clenching on the tin foil and on the protrusion preventing bite
      registration material, respectively, the vertical and horizontal condylar
      position was measured using a 6 d.f. ultrasonic motion analyser. Clenching with
      maximal force on the tin foil lead to a noticeable anterior downward directed
      movement of the condyle. Clenching on the protrusion preventing pivot, however,
      caused a statistically significant upward condylar movement of about 0.3 mm.
      These results indicate that occlusal pivots have no distractive effect on the
      temporomandibular joint but can lead to unwanted joint compression, if they are
      designed in a way that is preventing protrusion.

PMID- 17207077
TI  - Influence of attachment wear on retention of mandibular overdenture.
AB  - The aims of this study were: (i) to evaluate and compare retention of two-teeth
      (implant) supported mandibular overdenture with either stud or magnetic
      attachments during linear (axial) and rotational (paraxial) dislodgements; (ii)
      to compare retentive properties before and after wear simulation. The test group
      consisted of five magnetic and four stud overdenture attachments (n = 12
      specimens for each attachment type). Retention in axial direction was evaluated
      on one-tooth (implant) model by measuring maximum retentive force (N) and range
      of retention (mm) during the linear dislodgement. Retention in the paraxial
      direction was evaluated on mandibular-overdenture model by measuring the maximum
      retentive force (N) during three types of rotational dislodgements - anterior,
      lateral and posterior. The minimum number of cycles required to simulate wear was
      determined by special wear test. Afterwards, the wear was simulated in the test
      group, and retention in axial and paraxial directions was measured again.
      STATISTICAL ANALYSIS: one-way anova, Scheffe post hoc and paired-samples t-tests
      (P < 0.05). Initially, studs had higher retention (4-11 N) than magnets (4.5-6 N)
      in axial direction. After the wear simulation, it had decreased from 76% to 48%
      for some of the studs and had become similar to the retention of magnetic
      attachments. Magnets had lower retention range (0.2-0.3 mm) than studs (0.5-1.1
      mm). Studs provided similar or higher retention in paraxial directions than
      magnetic attachments both before and after wear simulation. Retentive properties
      of magnets decreased mostly with posterior rotational dislodgement. Retentive
      properties of stud overdenture attachments were less constant.

PMID- 17207078
TI  - Effect of implant support on distal extension removable partial dentures: in
      vitro assessment.
AB  - The implants in implant-supported removable partial dentures (RPDs) are placed in
      the edentulous ridge to stabilize the RPD and minimize the resultant rotational
      movement. This study investigated the effect of implant placement on RPD
      stability. A model simulating a mandibular bilateral distal extension missing was
      fabricated using epoxy resin and silicone impression material as thin (1 mm) and
      thick (2 mm) soft tissues. Five pressure sensors (PS-10K, Kyowa, Tokyo, Japan)
      were attached near the left and right first molars (#36 and #46), first premolars
      (#34 and #44) and medio-lingual alveolar crest. Five bilateral distal extension
      RPDs with Co-Cr frameworks were conventionally fabricated. After the implants
      were placed at the bilateral second molar areas, healing caps (4.5 mm high) were
      connected to the denture base with autopolymerized resin to support the RPD. As
      in a conventional RPD, sealing screws were placed without connecting them. Loads
      up to 5 kg were applied, and the pressure and displacement of the RPDs (n = 5)
      were simultaneously measured and analysed using the Wilcoxen test (alpha = 0.05).
      There was less pressure on both thin and thick soft tissues, the #36, #46 and the
      medio-lingual alveolar crest from the implant-supported RPD than from the
      conventional RPD (P < 0.05). There were no significant differences in pressure on
      #34 and #44 between the two RPDs (P > 0.05). There was significantly less denture
      displacement of the implant-supported RPD than of the conventional denture (P <
      0.05). Implant support helped prevent the displacement of distal extension RPDs
      and decreased the pressure on soft tissues.

PMID- 17207079
TI  - Attachment and proliferation of human periodontal ligament fibroblasts on
      bioactive glass modified ceramics.
AB  - In this study, six groups of modified ceramic specimens were constructed and were
      studied comparatively with dental porcelain (P:control) for their ability to
      support human periodontal ligament fibroblasts attachment and proliferation. The
      dental porcelain was initially coated with bioactive glass (PCB) or with a
      mixture of porcelain and bioactive glass (PCBP) and then calcium-phosphate rich
      (Ca-P) or hydroxy-carbonate apatite (HCAp) layers were bio-mimetically developed
      on both surfaces (PCB and PCBP) after immersion in simulated body fluid. The
      development and characterization of Ca-P and HCAp layers on PCBCa-P, PCBHCAp,
      PCBPCa-P, PCBPHCAp specimens' surfaces were evaluated by Scanning Electron
      Microscopy (SEM) and further confirmed by Fourier Transform Infrared Spectroscopy
      (FTIR). The modified ceramics differed from their controls concerning their
      surface morphology as evaluated by SEM, and their surface chemical composition
      (Al, P, Si, Ca, Na and K) as evaluated by Energy Dispersive Spectroscopy (EDS).
      Almost all modified specimens supported cell attachment, spreading and
      proliferation at higher extent than the control porcelain specimens. The
      additional layers of Ca-P or HCAp on PCBP and PCB specimens were found to
      positively affect cell attachment and proliferation. The highest cell population,
      of all specimens tested, was observed on PCBPCa-P and PCBPHCAp. The Ca-P
      particles present on all Ca-P and HCAp coated specimens seemed to be involved in
      cell adhesion.

PMID- 17207080
TI  - Surface characteristics of aesthetic restorative materials - an SEM study.
AB  - To determine the degree of surface roughness of glass-ionomer cements (GICs) and
      polyacid-modified resin composite (PAMRC) after polishing and immersion in
      various foodstuffs. Three tooth-coloured restorative materials were used: a PAMRC
      (F2000), a conventional glass-ionomer cement (CGIC) (Fuji IX) and a resin
      modified glass-ionomer cements (RM-GIC) (Fuji II LC). Disk-shaped specimens were
      prepared and tested with either a plastics matrix finish or after polishing with
      wet silicon carbide papers up to 2000-grit. All specimens were immersed in 37
      degrees C-distilled water for 1 week, followed by three different foodstuffs (red
      wine, coffee or tea) for a further 2 weeks. Replicas of specimens were prepared
      by taking polyvinyl siloxane impressions, casting in epoxy resin, gold sputter
      coating and examining using a Field-Emission Scanning Electron Microscope. The
      polished and matrix finish specimens of F2000 showed many microcracks at low
      magnification, and eroded surfaces with missing and protruding particles at high
      magnification in the polished specimens. The surface-polished specimens of Fuji
      II LC were considerably rougher than the matrix-finish specimens, with large
      voids and protruding filler particles. The effects of foodstuffs on Fuji II LC
      and F2000 were not noticeable. The CGIC became noticeably rougher after exposure
      to coffee and tea. All specimens had the smoothest surface when they were cured
      against a plastics matrix strip, and all materials had a rougher surface after
      polishing. None of the foodstuffs produced a perceptible increase in roughness on
      RM-GIC and PAMRC surfaces, whereas coffee and tea markedly increased the surface
      roughness of Fuji IX.

PMID- 17207082
TI  - Efficacies of caspofungin and a combination of caspofungin and meropenem in the
      treatment of murine disseminated candidiasis.
AB  - Disseminated candidiasis is relatively common in immunocompromised patients. The
      treatment protocol of these patients usually includes broad-spectrum antibiotics
      and also emprical antifungals initiated due to unresponsiveness to antibiotics.
      In this study the efficacies of caspofungin and meropenem - separately and
      together - in mice with disseminated candidiasis were studied. Immunocompetent
      mice were infected intravenously with 2x10(6) CFU of Candida albicans. At 24 h
      postinfection, intraperitoneal therapy was initiated and was continued for 7
      days. Therapy groups included those given caspofungin (0.5, 1.25, 5 mg/kg/day),
      meropenem (20 mg/kg/day), and a combination of the two drugs. The outcome of
      therapy was evaluated by kidney tissue burden studies and histologic examination.
      In vitro, drug susceptibilities were tested by checkerboard analysis. Kidney CFU
      counts showed that mice that had received both drugs had lower residual burdens.
      Caspofungin was effective at doses of 0.5, 1.25, 5 mg/kg compared to infected
      untreated controls. In vitro, MICs of caspofungin and meropenem were <0.075 micro
      g/ml and >64 micro g/ml, respectively. Synergism was observed with the
      combination. Histopathology showed that the degree of inflammation was 25% less
      and tubular necrosis was more restricted in combined therapy than monotherapy.
      The results indicate that concurrent caspofungin and meropenem therapy may be
      beneficial.

PMID- 17207083
TI  - Pyrosequencing of the DNA gyrase gene in Neisseria species: effective indicator
      of ciprofloxacin resistance in Neisseria gonorrhoeae.
AB  - The quinolone resistance determining region (QRDR) of the gyrA gene in
      ciprofloxacin-susceptible strains (n=53) and strains of Neisseria spp. with
      reduced susceptibility (n=70) was determined by the pyrosequencing method.
      Results showed that the QRDR of the gyrA gene is an effective molecular indicator
      of resistance to ciprofloxacin in Neisseria gonorrhoeae, and presumably in
      Neisseria meningitidis, but not in all other Neisseria spp. This sequence was not
      unique for N. gonorrhoeae and seems unsuitable for species verification of N.
      gonorrhoeae. However, whether it is also possible to use this region for
      verification depends on the specificity of the primary screening method used.

PMID- 17207084
TI  - Levels and interactions of plasma xanthine oxidase, catalase and liver function
      parameters in Nigerian children with Plasmodium falciparum infection.
AB  - Elevated plasma levels of xanthine oxidase and liver function parameters have
      been associated with inflammatory events in several human diseases. While
      xanthine oxidase provides in vitro protection against malaria, its
      pathophysiological functions in vivo and interactions with liver function
      parameters remain unclear. This study examined the interactions and plasma levels
      of xanthine oxidase (XO) and uric acid (UA), catalase (CAT) and liver function
      parameters GOT, GPT and bilirubin in asymptomatic (n=20), uncomplicated (n=32),
      and severe (n=18) falciparum malaria children aged 3-13 years. Compared to age
      matched control (n=16), significant (p<0.05) elevation in xanthine oxidase by 100
      550%, uric acid by 15.4-153.8%, GOT and GPT by 22.1-102.2%, and total bilirubin
      by 2.3-86% according to parasitaemia (geometric mean parasite density (GMPD)=850
      87100 parasites/microL) was observed in the malarial children. Further comparison
      with control revealed higher CAT level (16.2+/-0.5 vs 14.6+/-0.4 U/L; p<0.05)
      lacking significant (p>0.05) correlation with XO, but lower CAT level (13.4-5.4
      U/L) with improved correlations (r=-0.53 to -0.91; p<0.05) with XO among the
      asymptomatic and symptomatic malaria children studied. 75% of control, 45% of
      asymptomatic, 21.9% of uncomplicated, and none of severe malaria children had Hb
      level>11.0 g/dL. Multivariate analyses further revealed significant (p<0.05)
      correlations between liver function parameters and xanthine oxidase (r=0.57-0.64)
      only in the severe malaria group. We conclude that elevated levels of XO and
      liver enzymes are biochemical features of Plasmodium falciparum parasitaemia in
      Nigerian children, with both parameters interacting differently to modulate the
      catalase response in asymptomatic and symptomatic falciparum malaria.

PMID- 17207085
TI  - Detection of Helicobacter pylori DNA in peripheral blood from patients with
      peptic ulcer or gastritis.
AB  - Cases of Helicobacter bacteremia have been reported from time to time.
      Helicobacter pylori is the most important representative of Helicobacterium, yet
      whether it can result in bacteremia has rarely been studied. In this study, we
      examined H. pylori DNA in peripheral blood and gastric mucosa of patients with
      peptic ulcer or chronic gastritis by polymerase chain reaction (PCR). We found H.
      pylori DNA in 15 of 20 gastric samples, and 9 of these specimens were positive
      for H. pylori culture. H. pylori DNA amplified by PCR was positive in the
      peripheral blood of three patients, who all had duodenal ulcers. Gastric biopsy
      specimens from these three patients were all positive for H. pylori genes and H.
      pylori was isolated from these specimens. After the 16S rRNA gene sequences of
      three specimens from the same patient were obtained, we found that they were
      identical, which suggested that they are the same strain. Our findings suggest
      that H. pylori exists not only in gastric mucosa but also in peripheral blood,
      and it is possible that H. pylori can result in bacteremia.

PMID- 17207086
TI  - Differential phospholipase gene expression by Candida albicans in artificial
      media and cultured human oral epithelium.
AB  - Phospholipases B1, B2, C and D of Candida albicans play a significant role in the
      host invasive process. Hence we evaluated the in vitro expression of PLB1, PLB2,
      PLC1 and PLD1 in phospholipase-positive (PL(+)) and -deficient (PL(-)) C.
      albicans isolates in egg yolk agar (EYA), yeast peptone dextrose broth (YPD), and
      in a model of oral candidiasis based on reconstituted human oral epithelium
      (RHOE). The growth of Candida was then determined in YPD and its cellular
      invasion was investigated using the RHOE model. The PL(+) group demonstrated
      PLB1, PLB2, PLC1 and PLD1 expression in both EYA and YPD, in contrast to the PL(
      ) group, which expressed only PLB2 and PLD1. Although PL(+) isolates grew
      profusely in the RHOE model, they expressed only PLB2, PLC1 and PLD1, and not
      PLB1. Gene expression investigations could not be carried out with PL(-) isolates
      due to their inability to grow in the RHOE model. Significant growth differences
      in YPD medium were also observed within the PL(+) and PL(-) groups. Taken
      together, these findings indicate that phospholipase gene expression in C.
      albicans is differentially affected by their growth milieu, and this in turn may
      modulate the disease outcomes in vivo.

PMID- 17207087
TI  - Immunohistochemical and mutational analysis of apoptosis-inducing factor (AIF) in
      colorectal carcinomas.
AB  - Apoptosis-inducing factor (AIF) has a principal role in caspase-independent
      apoptosis. In addition, AIF has a vital oxidoreductase activity that is required
      for cell survival. It may be important to identify the alterations of the AIF
      gene and AIF protein expression to see the function of AIF in human cancers. In
      this study we analyzed the expression of AIF protein in 103 colorectal carcinomas
      by immunohistochemistry. We also analyzed the mutation in exons 10-15 of AIF
      encoding the region that possesses the cell death function of AIF by single
      strand conformation polymorphism (SSCP) in 48 colorectal, 48 gastric, 48 breast
      and 48 hepatocellular carcinomas, and 48 leukemias. By immunohistochemistry, AIF
      protein expression was detected in both cancer cells and normal mucosal
      epithelial cells in all of the 103 colorectal carcinoma tissues. However, the
      cancer cells showed higher intensities of AIF immunostaining than the normal
      cells in 83 cases (80.5%). AIF immunoreactivities were observed in the cancers
      irrespective of their location or the depth of invasion. Mutational analysis
      detected one AIF mutation in the colorectal carcinomas, but none in the other
      cancers. The AIF mutation detected was a two-base deletion mutation in intron 15.
      The increased expression of AIF in the malignant colorectal epithelial cells
      compared to the normal mucosal epithelial cells suggests that AIF expression may
      play a role in colorectal tumorigenesis. The data also suggest that somatic
      mutation of AIF is a rare event in common human cancers.

PMID- 17207088
TI  - Advanced glycation end products induce actin rearrangement and subsequent
      hyperpermeability of endothelial cells.
AB  - This study aimed to determine the effects of advanced glycation end products
      (AGEs) on endothelial cytoskeleton morphology and permeability, and to detect the
      underlying signaling mechanisms involved in these responses. Cultured endothelial
      cells (ECs) were exposed to AGE-modified human serum albumin (AGE-HSA), and EC
      cytoskeletal changes were evaluated by observing fluorescence of F-actin
      following ligation with labeled antibodies. Endothelial permeability was detected
      by measuring the flux of TRITC-albumin across the EC monolayers. To explore the
      signaling pathways behind AGE-induced EC alteration, ECs were treated with either
      soluble anti-AGE receptor (RAGE) IgG, or the MAPK inhibitors PD98059 and SB203580
      before AGE-HSA administration. To further elucidate possible involvement of the
      ERK and p38 pathways in AGE-induced EC changes, adenovirus-carried recombinant
      constitutive dominant-negative forms of upstream ERK and p38 kinases, namely
      MEK1(A) and MKK6b(A), were pre-infected into ECs 24 h prior to AGE-HSA exposure.
      AGE-HSA induced actin cytoskeleton rearrangement, as well as EC
      hyperpermeability, in a dose and time-dependent manner. The effects were
      attenuated in cells pretreated with anti-RAGE IgG, PD98059 or SB203580,
      respectively. EC pre-infection with MEK1(A) and MKK6b(A) also alleviated the
      effect of AGEs. Furthermore, adenovirus-mediated administration of activated
      forms of either MEK1 or MKK6b alone induced rearrangement of F-actin and
      hyperpermeability. The results indicate that ERK and p38 MAPK play important
      roles in the mediation of AGE-induced EC barrier dysfunction associated with
      morphological changes of the F-actin.

PMID- 17207089
TI  - Performance of combined clinical mammography and needle biopsy: a nationwide
      study from Denmark.
AB  - Clinical mammography and needle biopsy are key tools for non-operative assessment
      of breast lesions. We evaluated the performance of all combined tests undertaken
      in Denmark in 2000. Clinical mammography and needle biopsy data were collected
      and linked to final cancer outcome, to determine sensitivity, specificity, and
      predictive values of clinical mammography, needle biopsy, and combined test. In
      2000, 6709 combined tests were performed in 36 mammography clinics in Denmark.
      The combined test was consistently more sensitive than any single test,
      increasing the proportion of women correctly identified with breast cancer by 9%
      compared with clinical mammography alone. For concordant combined tests (i.e.
      either both benign or both malignant), specificity and positive predictive value
      were 100%, sensitivity was 99.1%, and positive predictive value was 99.6%.
      Therefore, Danish patients with a malignant concordant combined test can proceed
      directly to definitive surgery without fear of a false-positive diagnosis, and
      Danish women with a concordant benign combined test can omit surgery without fear
      of a false-negative diagnosis. In discordant cases, our results showed that any
      of the two tests with a suspicious or malignant result indicated a high risk of
      cancer, and excisional diagnostic biopsy therefore still has an important role to
      play.

PMID- 17207090
TI  - Immunohistochemical analysis of Omi/HtrA2 expression in prostate cancer and
      benign prostatic hyperplasia.
AB  - The serine protease Omi/HtrA2 is released from mitochondria into the cytosol
      after apoptotic stimuli, inducing apoptosis in a caspase-independent manner
      through its protease activity and in a caspase-dependent manner by neutralizing
      the inhibition of inhibitor of apoptosis proteins (IAPs) on caspases. Alteration
      of apoptosis is essential for cancer development, and cancer cell death by
      radiation and chemotherapy is largely dependent upon apoptosis. Thus, analysis of
      the expression status of Omi/HtrA2, a regulator of apoptosis, in cancer tissues
      is needed for an understanding of cancer development. In the current study we
      analyzed the expression of Omi/HtrA2 in 65 prostate cancer, 40 benign prostatic
      hyperplasia and 10 normal prostate specimens by immunohistochemistry. Omi/HtrA2
      mRNA levels of in vivo prostate cancer and benign prostatic hyperplasia samples
      were also assayed by semiquantitative reverse transcription-polymerase chain
      reaction. Immunopositivity (defined as > or =30%) was observed for Omi/HtrA2 in
      most of the prostate cancers, and the positive rate of Omi/HtrA2 was lower in the
      well-differentiated group than in the poorly and moderately differentiated groups
      (p<0.005). By contrast, the cells in the normal prostate and benign prostatic
      hyperplasia groups showed no or only weak expression of Omi/HtrA2. Meanwhile, the
      Omi/HtrA2 mRNA level of prostate cancer is much higher than that of benign
      prostatic hyperplasia (p<0.001). Taken together, these results suggest that
      prostate cancer cells in vivo may need Omi/HtrA2 expression for apoptosis, and
      that Omi/HtrA2 expression might be involved in prostate cancer development.

PMID- 17207091
TI  - Mendelian analysis of a metastasis-prone substrain of BALB/c nude mice using a
      subcutaneously inoculated human tumour.
AB  - Most nude mice do not allow the formation of metastases after
      heterotransplantation of human malignant tumours. Here we describe a substrain of
      BALB/c nude mice (BALB/c/AnNCr) that reproducibly allows some human cancers to
      metastasize. By Mendelian analysis of hybrids between this substrain and C57BL/6J
      +/+ mice we found that the ability to allow a human tumour (MDA-MB-435 BAG) to
      express its metastatic phenotype is determined by a recessively inheritable trait
      in the mouse host. We are presently working to identify the genetics responsible
      for development of metastases. The study also includes immunohistochemical and
      electron microscopic analysis of the test tumour, originally assumed to be a
      human mammary carcinoma, but shown to possess characteristics of a malignant
      melanoma (1). The ultimate aim of our ongoing study is to establish a substrain
      of nude mice that will allow metastasis in all recipients.

PMID- 17207092
TI  - Bridging necrosis and reticulin bridging fibrosis induced by intrahepatic
      involvement of acute biphenotypic leukemia.
AB  - A 47-year-old Japanese woman was diagnosed as having acute biphenotypic leukemia
      with association of t(9;22)(q34;q11). Cholestatic liver dysfunction arose, and
      she died of cachexia and intracranial hemorrhage. Autopsy showed unusual hepatic
      fibrosis. In the liver, bridging infiltration, bridging necrosis and bridging
      fibrosis by leukemic cells were seen. It seemed that the degree of fibrosis was
      associated with the number of aggregates of infiltrating leukemic cells. The
      fibrotic foci were predominantly composed of reticulin and collagen fibers, and
      distortion of the lobules was observed. Immunohistochemically, dense bundles of
      alpha-smooth muscle actin (ASMA)-positive stromal cells, namely activated hepatic
      stellate cells (HSCs), were observed in the immature fibrotic foci as well as
      along the sinusoids densely infiltrated by leukemic cells. No cells positive for
      TGF-beta1 or PDGF-BB were identified. In conclusion, extensive intrahepatic
      involvement by neoplastic cells in adult acute biphenotypic leukemia may cause
      the unusual "disorganized" hepatic fibrosis.

PMID- 17207093
TI  - Favourable effect of TNF-alpha inhibitor (infliximab) on Blau syndrome in
      monozygotic twins with a de novo CARD15 mutation.
AB  - Blau syndrome is a hereditary granulomatous disease caused by mutations in the
      CARD15 gene that is diagnosed in children of young age with exanthema/erythema,
      arthritis/periarthritis and/or uveitis. We report two cases of Blau syndrome in
      Danish Caucasian monozygotic male twins, exhibiting a heterozygous de novo R334W
      mutation in codon 334 of CARD15. The patients were initially diagnosed as having
      sarcoidosis. In both twins, symptoms (exanthema, arthritis/periarthritis) started
      at 1 year of age, and were followed by uveitis at 7-10 years of age. There was no
      involvement of the lungs or other organs. An initial course of standard
      antituberculous treatment had no effect on the symptoms. Hydroxychloroquine and
      cyclosporine A were also ineffective, and the latter caused impaired renal
      function. Partial symptomatic relief was obtained with prednisolone and increased
      benefit was observed in combination with methotrexate. Subsequent introduction of
      the TNF-alpha inhibitor eternacept did not discernibly benefit the clinical
      condition, but was associated with recurrent infections. In contrast, a trial of
      infliximab therapy demonstrated clinical efficacy and eliminated all symptoms,
      restoring a high quality of life. At follow up at 20 years of age (after 2-5
      years of infliximab treatment) the twins had an almost normal physical appearance
      and a normal psychomotoric development, indicating a favourable short-term
      prognosis of the disease. Blau syndrome has pathologic, clinical and therapeutic
      features in common with sarcoidosis, but rarely involves the lungs or other
      parenchymatous organs. In children, discrimination between early onset
      sarcoidosis and Blau syndrome should include a CARD15 mutation analysis.

PMID- 17207095
TI  - A functional polymorphism of the mu-opioid receptor gene (OPRM1) influences cue
      induced craving for alcohol in male heavy drinkers.
AB  - BACKGROUND: The mu-opioid receptor gene (OPRM1) codes for the mu-opioid receptor,
      which binds beta-endorphin. The A118G polymorphism in this gene affects beta
      endorphin binding such that the Asp40 variant (G allele) binds beta-endorphin 3
      times more tightly than the more common Asn40 variant (A allele). This study
      investigated the influence of the A118G polymorphism on cue reactivity after
      exposure to an alcoholic beverage in male heavy drinkers. METHODS: Participants
      were either homozygous for the A allele (n=84) or carrying at least 1 copy of the
      G allele (n=24). All participants took part in a cue-reactivity paradigm where
      they were exposed to water and beer in 3-minute trials. The dependent variables
      of main interest were subjective craving for alcohol, subjective arousal, and
      saliva production. RESULTS: G allele carriers reported significantly more craving
      for alcohol than the A allele participants (as indicated by the within-subject
      difference in craving after beer vs after water exposure). No differences were
      found for subjective arousal and saliva. Both groups did not differ in family
      history of alcoholism. Participants with the G allele reported a significantly
      higher lifetime prevalence of drug use than participants homozygous for the A
      allele. CONCLUSIONS: A stronger urge to drink alcohol after exposure to an
      alcoholic beverage might contribute to a heightened risk for developing alcohol
      related problems in individuals with a copy of the G allele. The G allele might
      also predispose to drug use in general.

PMID- 17207096
TI  - The gamma-aminobutyric acid-B receptor agonist baclofen attenuates responding for
      ethanol in ethanol-dependent rats.
AB  - BACKGROUND: Gamma-aminobutyric acid-B (GABA(B)) receptor agonists have been shown
      to suppress operant self-administration of ethanol in nondependent rats. However,
      little work has focused on the effects of GABA(B) receptor agonists on self
      administration of ethanol in dependent animals. METHODS: In the present
      experiment, the GABA(B) receptor agonist baclofen was tested for the ability to
      modulate both fixed- (FR) and progressive-ratio (PR) responding for ethanol in
      rats while nondependent and subsequently after ethanol dependence induction.
      Following the acquisition and stabilization of baseline operant ethanol self
      administration and after dependence induction, baclofen [0.0, 0.5, 1, 2, and 4
      mg/kg, intraperitoneal (IP)] was tested on FR-1 responding for ethanol. The
      ability of baclofen (2.0 mg/kg) to affect responding under a PR schedule of
      reinforcement was also evaluated. Dependence was induced in the animals by
      subjecting them to a 1-month intermittent vapor-exposure period in which animals
      were exposed to ethanol vapor for 14 h/d. Following the 1-month period, the vapor
      exposed animals resumed FR-1 and PR baclofen drug testing (doses as described
      above) in the operant chambers at a time point corresponding to the animals being
      6 hours into withdrawal (i.e., 6 hours after the ethanol vapor had been
      discontinued for that day). RESULTS: Baclofen (0.0, 0.5, 1, 2, and 4 mg/kg, IP)
      dose-dependently decreased ethanol self-administration in both nondependent and
      dependent rats on a FR schedule of reinforcement. However, the dose of baclofen
      that significantly reduced responding for ethanol was shifted to the left in the
      ethanol vapor-exposed animals, indicating an increased sensitivity to baclofen in
      animals that were chronically exposed to ethanol. When tested using a PR schedule
      of reinforcement, there was a significant increase in the breakpoint for the
      vapor-exposed animals (i.e., the animals were willing to work more in a dependent
      state). Baclofen (2.0 mg/kg, IP) suppressed intake for both nondependent and
      dependent animals. CONCLUSIONS: Ethanol dependence produced increased self
      administration of ethanol as reflected in increased ethanol intake and increased
      responding on a PR schedule of reinforcement. As baclofen suppressed ethanol self
      administration and showed evidence of increased potency in dependent animals, the
      present experiment suggests that the GABA(B) receptor could be a potential
      pharmacotherapeutic target for the treatment of chronic alcoholism.

PMID- 17207097
TI  - Sleep electroencephalographic spectral power after withdrawal from alcohol in
      alcohol-dependent patients.
AB  - BACKGROUND: Dysfunctional hyperarousal is suspected to be a neurophysiological
      determinant of relapse in abstinent alcohol-dependent patients. In the present
      study, we used spectral power analysis of the sleep electroencephalographic (EEG)
      to quantify brain activity during sleep in patients during subacute withdrawal as
      well as in control subjects. Our hypothesis was that the subgroup of patients who
      relapsed within the 3 months to follow-up would exhibit-increased dysfunctional
      arousal manifested by higher-frequency (beta) EEG power during sleep. METHODS:
      Twenty-six alcohol-dependent in-patients were examined with polysomnography over
      2 nights 2 to 3 weeks after withdrawal. At the 3-month clinical follow-up
      assessment, 12 of them had relapsed and 14 abstained. The control group consisted
      of 23 healthy subjects similar to the patients with alcohol dependence in age and
      gender distribution. Spectral sleep EEG analysis was performed on both nights
      (adaptation and baseline) of all subjects. Logarithmic artifact-controlled
      spectral band power of sleep stage 2 and rapid eye movement (REM) sleep was
      analyzed for Group, Gender, and Age effects using multiple analyses of
      covariance. Three groups were compared with the Group factor: relapsers,
      abstainers, and controls. RESULTS: Generally, both Group and Age effects were
      significant for the second, baseline night for the visually scored sleep
      parameters, while spectral EEG parameters showed significant differences in the
      adaptation night. In the adaptation night, a significant enhancement in the beta2
      band (24-32 Hz) was seen in REM sleep in relapsers relative to both abstainers
      and controls. CONCLUSIONS: The beta2 increase could be interpreted as a sign of
      dysfunctional arousal during REM sleep "unmasked" by the additional stressor of
      sleep environment adaptation. Its determinants are likely to be both premorbid
      and drinking history related.

PMID- 17207098
TI  - PET [11C]DASB imaging of serotonin transporters in patients with alcoholism.
AB  - OBJECTIVE: Alcoholism and aggression have each been associated with neurochemical
      measurements suggestive of decreased serotonin synaptic transmission. We measured
      densities of the serotonin transporter (SERT) in a moderate-sized sample of
      alcoholic patients who were assessed for aggressive characteristics. METHODS:
      Thirty alcoholic inpatients and 18 healthy controls received a PET scan with
      [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile. The
      alcoholic inpatients were classified as aggressive or nonaggressive based on a
      comparison between the top third and bottom third scores on the Buss-Durkee
      Hostility Index. RESULTS: Using a pixel-wise comparison, no brain region showed
      significant alterations in SERT binding among the 3 groups of subjects
      (aggressive alcoholic subjects, nonaggressive alcoholic subjects, and healthy
      controls) or between the combined alcoholic group and healthy controls. None of
      the clinical measures (including measures of aggression) correlated with SERT
      binding in the alcoholic subjects. CONCLUSION: Contrary to prior imaging reports
      using the nonselective ligand [(123)I]beta-CIT, we found no significant
      alterations of SERT density in alcoholic patients.

PMID- 17207099
TI  - Is alcohol use associated with cavitary disease in tuberculosis?
AB  - BACKGROUND: Alcohol mediates detrimental alterations in the immune response to
      Mycobacterium tuberculosis. The association between quantity and frequency of
      alcohol use and the prevalence of cavitary disease in tuberculosis (TB) has not
      been analyzed. To investigate the relationship of alcohol use and the prevalence
      of cavitary disease in a 6-year population-based data set of individuals with TB.
      METHODS: We assessed quantity and frequency of alcohol use (daily alcohol use,
      years of alcohol use, and lifetime alcohol use) with a standardized
      questionnaire. The study group consisted of 1,250 patients analyzed for cavitary
      disease (HIV sero-negative subjects that were 18 years or older). Significant
      covariates for cavitary disease were entered into multiple logistic regression
      models. RESULTS: Although daily alcohol use, years of alcohol use, and alcohol
      use 30 days or 6 months before symptom onset were significant predictors of
      cavitary disease in univariate analysis, no independent associations were found
      between alcohol use and cavitary disease in the multivariate analysis. Only
      diabetes mellitus was independently associated with cavitary disease at any level
      or frequency of alcohol use. CONCLUSION: Alcohol use is not independently
      associated with increased prevalence of cavitary disease in adult patients with
      TB.

PMID- 17207100
TI  - Development of naltrexone supersensitivity during food-maintained responding
      enhances naltrexone's ability to reduce ethanol-maintained responding.
AB  - BACKGROUND: Similar doses of the opiate antagonist naltrexone (NTX) reduce
      responding maintained by food and ethanol. In animals responding for food,
      repeated administration of NTX produces supersensitivity to NTX. The purpose of
      this study was to determine whether the factors that produce enhanced sensitivity
      to NTX during food-maintained responding also contribute to NTX's ability to
      reduce ethanol-maintained responding. METHODS: Rats (n=12) were trained to lever
      press using food reinforcement. After responding stabilized, the rats were
      trained to respond for 10% ethanol. Before ethanol sessions, injections of 30
      mg/kg NTX were given. Subsequently, weekly cumulative NTX dose-effect curves (1,
      3, 10, 30, and 100 mg/kg), known to produce NTX supersensitivity, were determined
      during food-maintained responding in half the rats for 8 weeks while the other
      half of the rats received saline vehicle injections instead. To determine whether
      NTX supersensitivity would transfer to ethanol self-administration, ethanol
      maintained responding was re-established and 30 mg/kg NTX was administered again.
      RESULTS: Initially, 30 mg/kg NTX had little effect on ethanol-maintained
      responding. During food-maintained responding, supersensitivity developed in rats
      receiving weekly cumulative NTX injections. After development of
      supersensitivity, 30 mg/kg decreased ethanol-maintained responding. Naltrexone's
      potency to reduce ethanol-maintained responding was unchanged in rats that
      received only vehicle injections for 8 weeks. CONCLUSION: The mechanisms that
      produce NTX supersensitivity during food-maintained responding may play a role in
      NTX's effect on ethanol consumption. Naltrexone's effect on responding for
      ethanol was much smaller than that reported in other studies. Further exploration
      may lead to techniques that maximize NTX's effect on ethanol while minimizing its
      effect on other behaviors.

PMID- 17207101
TI  - Ethnic disparities in clinical severity and services for alcohol problems:
      results from the National Alcohol Survey.
AB  - BACKGROUND: This study reports lifetime estimates of the extent of unmet need for
      alcohol services across the 3 largest ethnic groups in America, and examines
      factors that may contribute to ethnic differences in service use. Prior studies
      report mixed findings as to the existence of ethnic disparities in alcohol
      services, with some suggesting that minorities are over-represented in treatment
      settings. METHODS: Drawing on the most recent National Alcohol Surveys, we
      compare rates and factors associated with the lifetime service use for alcohol
      problems among Whites, Blacks, and Hispanics who meet lifetime criteria for
      alcohol abuse or dependence. RESULTS: While bivariate analyses revealed few
      ethnic differences in service use, there were significant differences by
      ethnicity in multivariate models that included alcohol problem severity and its
      interactions with ethnicity. At higher levels of problem severity, both Hispanics
      and Blacks were less likely to have utilized services than comparable Whites.
      Hispanics, on the whole, reported higher-severity alcohol problems than Whites.
      Yet, they were less likely to have received specialty treatment and multiple
      types of alcohol services, and were more likely to cite economic and logistical
      barriers as reasons for not obtaining care. CONCLUSIONS: Future efforts to study
      ethnic disparities in alcohol services should utilize analytic approaches that
      address potential confounding between ethnicity and other factors in service use,
      such as alcohol problem severity. Our findings suggest that Hispanics and Blacks
      with higher-severity alcohol problems may utilize services at lower rates than
      comparable Whites, and that, particularly for Hispanics, this may in part be
      attributable to financial and logistical barriers to care.

PMID- 17207102
TI  - Effects of atypical anxiolytic N-phenyl-2-[1-[3-(2-pyridinylethynyl)benzoyl]-4
      piperidine]acetamide (JNJ-5234801) on alcohol intake in alcohol-preferring P
      rats.
AB  - BACKGROUND: N-Phenyl-2-[1-[3-(2-pyridinylethynyl)benzoyl]-4-piperidine]acetamide
      (JNJ-5234801) is a structurally novel atypical anxiolytic with an overall in vivo
      profile in animals suggestive of the potential to show anxiolytic efficacy in
      humans at doses that will not cause CNS-related side effects. Furthermore, unlike
      the benzodiazepines, JNJ-5234801 does not have an adverse interaction with
      ethanol even at doses 20 to 40 times the minimal effective dose in the rat
      elevated plus maze (MED=1.0 mg/kg, p.o.). METHODS: In the present study, JNJ
      5234801 was evaluated for potential efficacy in reducing alcohol intake in
      alcohol-preferring rats. Alcohol-preferring P rats were allowed to drink water or
      alcohol (10%, v/v) in a 2-bottle choice procedure. Once stable baselines were
      established, the acute effects of JNJ-5234801 [(10-40 mg/kg, intraperitoneally
      (i.p.)] were assessed. In a separate study, chronic treatment with JNJ-5234801
      (40 mg/kg once daily, i.p.) for 12 consecutive days was compared with naltrexone
      (20 mg/kg, twice daily, i.p.). RESULTS: There was a selective dose-dependent
      reduction in alcohol intake in the alcohol-preferring (P) rats after acute
      administration of JNJ-5234801 (10-40 mg/kg, i.p.). There were no significant
      effects on food or water intake. When administered subchronically, both JNJ
      5234801 (40 mg/kg once daily, i.p.) and naltrexone (20 mg/kg, twice daily, i.p.)
      considerably reduced alcohol intake, but tolerance to the alcohol-suppressing
      effects appeared to occur sooner in the naltrexone-treated group. While both
      compounds slightly but significantly reduced food intake at the beginning, only
      JNJ-5234801 increased water intake and decreased alcohol preference. CONCLUSIONS:
      The novel atypical anxiolytic JNJ-5234801 has a favorable profile effects on
      alcohol intake and related measures compared with naltrexone, which is
      recommended for the treatment of alcoholism.

PMID- 17207103
TI  - Encouraging posttreatment self-help group involvement to reduce demand for
      continuing care services: two-year clinical and utilization outcomes.
AB  - BACKGROUND: Accumulating evidence indicates that addiction and psychiatric
      treatment programs that actively promote self-help group involvement can reduce
      their patients' health care costs in the first year after treatment, but such
      initially impressive effects may wane over time. This paper examines whether the
      positive clinical outcomes and reduced health care costs evident 1 year after
      treatment among substance-dependent patients who were strongly encouraged to
      attend 12-step self-help groups were sustained at 2-year follow-up. METHODS: A 2
      year quasi-experimental analysis of matched samples of male substance-dependent
      patients who were treated in either 12-step-based (n=887 patients) or cognitive
      behavioral (CB, n=887 patients) treatment programs. The 12-step-based programs
      placed substantially more emphasis on 12-step concepts, had more staff members
      "in recovery," had a more spiritually oriented treatment environment, and
      promoted self-help group involvement much more extensively than did the CB
      programs. The 2-year follow-up assessed patients' substance use, psychiatric
      functioning, self-help group affiliation, and mental health care utilization and
      costs. RESULTS: As had been the case in the 1-year follow-up of this sample, the
      only difference in clinical outcomes was a substantially higher abstinence rate
      among patients treated in 12-step (49.5%) versus CB (37.0%) programs. Twelve-step
      treatment patients had 50 to 100% higher scores on indices of 12-step self-help
      group involvement than did patients from CB programs. In contrast, patients from
      CB programs relied significantly more on outpatient and inpatient mental health
      services, leading to 30% lower costs in the 12-step treatment programs. This was
      smaller than the difference in cost identified at 1 year, but still significant
      ($2,440 per patient, p=0.01). CONCLUSIONS: Promoting self-help group involvement
      appears to improve posttreatment outcomes while reducing the costs of continuing
      care. Even cost offsets that somewhat diminish over the long term can yield
      substantial savings. Actively promoting self-help group involvement may therefore
      be a useful clinical practice for helping addicted patients recover in a time of
      constrained fiscal resources.

PMID- 17207104
TI  - Impact of age at first drink on stress-reactive drinking.
AB  - BACKGROUND: Although recent data from animal models indicate that adolescent
      ethanol exposure increases self-administered ethanol intake in adult rats, the
      impact of age at first drink on the association between stress and drinking has
      not been studied in humans. METHODS: Data collected in the 2001 to 2002 National
      Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were used to
      estimate the extent to which age at first drink modified the association between
      stress and average daily volume (ADV) of ethanol intake in a sample of 26,946
      past-year drinkers. Successive models estimated the magnitude and significance of
      the interaction between age at first drink (ages 14 or younger, 15-17, and 18 or
      older) and number of stressors (out of 12 past-year negative life events) after
      (1) adjusting for sociodemographic characteristics, (2) additionally adjusting
      for family history of alcoholism, comorbid psychopathology, adolescent, and past
      year tobacco and illicit drug use, and (3) additionally adjusting for all other
      significant interactions with number of stressors. RESULTS: Even after adjusting
      for a wide range of confounders and their interactions with stress, initiation of
      drinking at ages 14 and younger increased the association between the number of
      stressors and ADV of ethanol consumption by 8% (p=0.014), when considering the
      full range of 12 potential stressors. In fact, the positive association between
      stress and consumption was significant only for this group of drinkers with early
      adolescent exposure to ethanol. Within this group, ADV of consumption increased
      by an average of 7% with each additional stressor experienced, although the exact
      percentage increase varied as a function of other covariates that had significant
      interactions with stress. When a reduced set of 4 stressors was considered, the
      magnitudes of the associations were mostly unchanged, but the modifying effect of
      age at first drink fell short of statistical significance (p=0.309) in the fully
      adjusted model. CONCLUSIONS: The findings of this study are consistent with the
      argument that early-onset drinking may increase stress-reactive ethanol
      consumption; however, these findings need to be replicated in an experimental
      human study in order to control fully the direction of the relationship between
      stress and consumption.

PMID- 17207105
TI  - Does the association between alcohol consumption and depression depend on how
      they are measured?
AB  - BACKGROUND: Inconsistent findings regarding the relationship between alcohol
      consumption and depression, including whether the relationship is J-shaped or U
      shaped, may be at least partly due to the types of measures used for both alcohol
      consumption and depression. METHODS: We conducted a general population survey
      using random digit dialing (RDD) and computer-assisted telephone interviewing
      (CATI) with 6,009 males and 8,054 females aged 18 to 76 years. The survey
      included 4 types of alcohol measures (frequency, usual and maximum quantity per
      occasion, volume, and heavy episodic drinking) covering both the past week and
      the past year, and 2 types of depression measures (meeting DSM criteria for a
      clinical diagnosis of major depression, recent depressed affect). RESULTS: The
      overall relationship between depression and alcohol consumption did not vary by
      gender or type of depression measure but did vary significantly by type of
      alcohol measure, with the strongest relationship found for heavy episodic
      drinking and high quantity per occasion. There were also significant gender
      interactions with both depression and alcohol measures, with females showing a
      stronger relationship than males when depression was measured as meeting the
      criteria for major depression and when alcohol consumption was measured as
      quantity per occasion or heavy episodic drinking. There was some evidence of a J
      shaped relationship, that is, greater depression among abstainers compared with
      those who usually drank 1 drink and never drank as much as 5 drinks for both
      former drinkers and lifetime abstainers when depression was measured as recent
      symptoms of depression but the J shape was found only for former drinkers when
      depression was measured as meeting the criteria for major depression and did not
      reach statistical significance in some analyses. CONCLUSIONS: The results of the
      present study suggest that measurement and gender are key issues in interpreting
      findings on the relationship between alcohol and depression. First, depression is
      primarily related to drinking larger quantities per occasion, less related to
      volume, and unrelated to drinking frequency, and this effect is stronger for
      women than for men. Second, the overall relationship between depression and
      alcohol consumption is stronger for women than for men only when depression is
      measured as meeting a clinical diagnosis of major depression and not when
      measured as recent depressed affect. Finally, while there was some evidence that
      former drinkers had slightly higher rates of major depression and higher scores
      on recent depressed affect compared with light drinkers, there was no evidence
      that light drinking was protective for major depression when compared with
      lifetime abstainers, although light drinkers did report fewer recent symptoms of
      depressed affect.

PMID- 17207106
TI  - Effects of ethanol on excitatory and inhibitory synaptic transmission in rat
      cortical neurons.
AB  - BACKGROUND: The gamma-aminobutyric acid-A (GABA(A)) receptor and glutamate
      receptors are among the most important target sites for the behavioral effects of
      ethanol. However, data in the literature concerning the ethanol modulation of the
      GABA(A) and glutamate receptors have been controversial. The activity of the
      neuronal nicotinic acetylcholine (ACh) receptors (nAChRs) has recently been
      reported to be potently augmented by ethanol. The activation of nAChRs is also
      known to cause the release of various neurotransmitters including GABA and
      glutamate. Thus, ethanol potentiation of nAChRs is expected to stimulate the
      GABAergic and glutamatergic systems. METHODS: Whole-cell patch clamp experiments
      were performed using rat cortical neurons in primary culture to record
      spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and spontaneous
      miniature excitatory postsynaptic currents (mEPSCs). RESULTS: Two types of
      neurons were distinguished: bipolar neurons possessed alpha4beta2 nAChRs
      generating a steady current in response to 30 nM ACh, and multipolar neurons that
      did not generate a current by ACh application. Acetylcholine greatly increased
      the frequency of mEPSCs and mIPSCs in bipolar neurons but not in multipolar
      neurons. The amplitude of neither type of neuron was affected by ACh. Ethanol at
      10 to 100 mM suppressed the amplitude of mEPSCs while augmenting the amplitude of
      mIPSCs in both bipolar and multipolar neurons, indicating the direct action on
      the respective receptors. In bipolar neurons, ACh plus 100 mM ethanol greatly
      increased the frequency of mIPSCs beyond the levels achieved by ACh alone, while
      no such increases were observed in multipolar neurons. CONCLUSIONS: It is
      concluded that ethanol stimulation of nAChRs modulates the activity of both
      glutamate and GABA receptors in rat cortical bipolar neurons.

PMID- 17207107
TI  - Apomorphine-induced growth hormone response is attenuated by ethanol but not
      dextromethorphan.
AB  - BACKGROUND: Misuse of alcohol drinking is a major health problem. Alcohol
      decreases spontaneous growth hormone (GH) secretion, but the mechanism is
      unclear. The aim of this study was to test whether administration of alcohol
      (study 1) or a N-methyl d-aspartate (NMDA) receptor antagonist (study 2)
      attenuates the GH response to pharmacological dopaminergic stimulation. METHODS:
      The 2-session repeated measures design was conducted at the endocrine laboratory
      at the Department of Psychiatry at the Free University Berlin. Twenty healthy
      Caucasian males aged 35+/-10 years without a history of alcohol use disorders
      were tested using the Apomorphine (APO) challenge test. In study 1, we injected
      APO (0.01 mg/kg s.c.) 1 hour after oral administration of 1 g/kg ethanol and
      placebo, respectively. In study 2, the APO challenge was conducted after 0.3
      mg/kg dextromethorphan (DXM) and placebo. The main outcome measures were the peak
      serum GH concentration and area under the time/concentration curve up to 120
      minutes after APO. The effects of ethanol and DXM were tested using the Wilcoxon
      signed-rank tests. RESULTS: Compared with placebo, alcohol significantly
      decreased the APO-induced GH release (mean and SEM peak GH concentration 19.9+/
      3.2 vs 6.2+/-1.9 ng/mL, p=0.002). Dextromethorphan did not change APO-induced GH
      response (22.5+/-5.4 vs 21.0+/-5.8 ng/mL, p=0.105). CONCLUSION: A single
      intermediate alcohol dose markedly reduces GH response to dopaminergic
      stimulation. Although alcohol is thought to stimulate dopaminergic function in
      certain pathways, but not necessarily in the hypothalamus, our results are in
      line with the alcohol effect on baseline GH secretion. Growth hormone suppression
      appears not to be mediated by ethanol's NMDA-antagonistic properties.

PMID- 17207108
TI  - Effect of chronic ethanol consumption on the response of parathyroid hormone to
      hypocalcemia in the pregnant rat.
AB  - BACKGROUND: Chronic alcohol (ethanol) consumption during pregnancy results in
      maternal/fetal hypocalcemia, which may underlie some of ethanol's adverse effects
      on maternal and fetal bone, and fetal/neonatal health. Ethanol appears to alter
      the relationship between parathyroid hormone (PTH) and blood calcium (Ca) level,
      and PTH does not increase in response to ethanol-induced hypocalcemia. However,
      it is not known whether ethanol actually prevents PTH from responding, or whether
      the ability to regulate blood Ca is intact, but ethanol lowers the level of Ca
      maintained. The objective of this study was to determine whether chronic ethanol
      consumption impairs the ability of the pregnant female to increase PTH in
      response to acute hypocalcemia. METHODS: Rats were fed isocaloric diets with
      ethanol (36% ethanol-derived calories, E group) or without ethanol [pair-fed (PF)
      and control (C) groups], before and throughout 21 days of gestation. On day 21
      gestation, rats received an intraperitoneal injection of ethylene glycol-bis
      (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) (300 or 500 mumol/kg
      body weight) or saline (saline group), or no injection (baseline group). Blood
      was collected from the baseline group, and at 30 or 60 minutes postinjection
      (saline and EGTA groups), and analyzed for ionized Ca (iCa), pH, and PTH.
      RESULTS: Consistent with previous studies, ethanol consumption decreased blood
      iCa levels at baseline, but PTH levels did not differ among groups.
      Administration of EGTA significantly decreased blood iCa levels by 30 minutes,
      but ethanol did not prevent PTH from increasing in response to the hypocalcemia.
      In all diet groups, PTH levels were significantly increased by 30 minutes.
      Ethanol did, however, appear to decrease the maximum PTH level achievable in
      blood. CONCLUSIONS: These data suggest that chronic ethanol consumption does not
      impair the ability of the pregnant rat to raise serum PTH levels in response to
      acute hypocalcemia, but ethanol's effect on maximal PTH secretion could impair
      the ability of the pregnant female to sustain high PTH levels in response to
      chronic hypocalcemia.

PMID- 17207109
TI  - Alcohol intoxication inhibits pulmonary S100A8 and S100A9 expression in rats
      challenged with intratracheal lipopolysaccharide.
AB  - BACKGROUND: Alcohol is known to inhibit the recruitment of polymorphonuclear
      leukocytes (PMNs) into tissue sites including the lung. During infection and
      inflammation, recruited neutrophils (PMNs) release S100 proteins that function to
      promote the recruitment of additional phagocytes. METHODS AND RESULTS: This study
      investigated the effects of alcohol intoxication on S100 protein production in
      the lung in response to lipopolysaccharide (LPS). Animals were administered
      alcohol (5.5 g/kg) or saline 30 minutes before intratracheal challenge with LPS
      (100 microg/rat). Alcohol suppressed PMN recruitment into the lung following
      intratracheal LPS, which was associated with an inhibition of increase in S100A8
      levels in both the bronchoalveolar lavage (BAL) fluid and lysates of cells
      recovered by BAL at 90 minutes and 4 hours post-LPS challenge. S100A8 and S100A9
      mRNA expression in cells recovered by BAL was significantly up-regulated at both
      90 minutes and 4 hours after the LPS challenge, and alcohol also suppressed this
      response. In addition, intratracheal LPS caused a transient increase in S100A8
      mRNA expression in circulating leukocytes at 90 minutes after the challenge.
      Similarly, this LPS-induced up-regulation of S100A8 mRNA expression was inhibited
      in rats intoxicated with alcohol. CONCLUSION: These data show that alcohol
      inhibits the S100 protein response in the lung, which may serve as a mechanism
      underlying alcohol-induced suppression of PMN recruitment into the terminal
      airways during pulmonary infection.

PMID- 17207110
TI  - Effect of chronic ethanol administration on the in vitro production of
      proinflammatory cytokines by rat Kupffer cells in the presence of apoptotic
      cells.
AB  - BACKGROUND: Chronic ethanol consumption can lead to a variety of pathological
      consequences by as yet undefined mechanisms. Recently, it has been noted that
      alcohol-associated liver disease is often accompanied by morphological liver
      changes that include the increased production of apoptotic cells. Additionally,
      it has been demonstrated that hepatocellular uptake and removal of potentially
      damaging apoptotic cells is impaired after ethanol treatment. The aim of the
      present study was to determine whether the presence of apoptotic cells leads to
      Kupffer cell (KC) production and release of proinflammatory cytokines that have
      been linked to hepatocyte damage, such as interleukin-6 (IL-6) and tumor necrosis
      factor alpha (TNF-alpha). METHODS: Kupffer cells were isolated from female rats
      after an 8-week oral administration of a dextrose control or ethanol-containing
      fish-oil diet. The isolated KCs were cultured for up to 24 hours in the absence
      or presence of apoptotic or nonapoptotic hepatoma cells, or lipopolysaccharide.
      After incubation, media from the cultures were assayed for the presence of TNF
      alpha and IL-6 by immunoassay detection. Also, the expression of these cytokines
      was measured in KC lysates by a quantitative real-time polymerase chain reaction.
      RESULTS: Kupffer cells cultured for up to 24 hours in the presence of apoptotic
      cells produced significantly more TNF-alpha and IL-6 (80 and 60%, respectively,
      p<0.05) when the cells were isolated from ethanol-fed animals compared with
      controls. Additionally, after as early as 4 hours in culture with apoptotic
      cells, mRNA levels of both cytokines were increased (2-5-fold) in KCs isolated
      from ethanol-fed animals compared with controls. CONCLUSIONS: The presence of
      apoptotic cells results in the in vitro activation of KCs. Additionally, chronic
      ethanol administration results in an enhanced responsiveness of KCs to produce
      proinflammatory cytokines indicated by the increased production of inflammatory
      mediators from KCs obtained from ethanol-fed animals.

PMID- 17207111
TI  - HIV-1 gp120 as well as alcohol affect blood-brain barrier permeability and stress
      fiber formation: involvement of reactive oxygen species.
AB  - BACKGROUND: HIV-1 infection commonly leads to serious HIV-1-associated
      neurological disorders, such as HIV-1-associated encephalopathy and dementia. In
      addition, alcohol is commonly used and/or abused among AIDS patients, but it is
      unclear whether alcohol affects the disease progression and if it affects it, how
      this occurs. We hypothesized that alcohol could affect the blood-brain barrier
      (BBB) integrity and thus could affect the onset and/or progression of HIV
      associated neurological disorders. METHODS: Human brain microvascular endothelial
      cells (HBMEC) in a BBB model system were pretreated with alcohol (17 and 68 mM)
      and subsequently coexposed with HIV-1 gp120. Expression of chemokine receptors
      CCR3, CCR5, and CXCR4 was assessed by enzyme-linked immunosorbent assay and real
      time polymerase chain reaction. Changes in the permeability of the HBMEC
      monolayer were assessed using paracellular markers [(3)H]inulin or propidium
      iodide. Actin rearrangements in HBMEC were visualized by fluorescence microscopy
      and viability assessed using Live/Dead stain. RESULTS: Both gp120 and alcohol
      increased the permeability of the BBB model by up to 141%, without affecting
      HBMEC viability. Cotreatment with alcohol and gp120 did not result in a
      significant synergistic effect. Gp120 permeability involved chemokine receptor
      CCR5. Alcohol did not affect chemokine receptor expression on brain endothelial
      cells. Both gp120 and alcohol reorganized the cytoskeleton and induced stress
      fiber formation. Inhibition of reactive oxygen species (ROS) formation through
      NADPH blocked the effects of both gp120 and alcohol on permeability and stress
      fiber formation. CONCLUSION: These results indicate that both HIV-1 gp120 and
      alcohol induce stress fibers, causing increased permeability of the human BBB
      endothelium. Alcohol (68 mM)-mediated permeability increase was linked to ROS
      formation. The alcohol-mediated physiological changes in the HBMEC monolayers may
      increase diffusion of plasma components and viral penetration across the BBB.
      This suggests that alcohol, especially at levels attained in heavy drinkers, can
      potentially contribute in a negative fashion to HIV-1 neuropathogenesis.

PMID- 17207112
TI  - Effects of alcohol consumption on iron metabolism in mice with hemochromatosis
      mutations.
AB  - BACKGROUND: Alcoholic liver disease is associated with increased hepatic iron
      accumulation. The liver-derived peptide hepcidin is the central regulator of iron
      homeostasis and recent animal studies have demonstrated that exposure to alcohol
      reduces hepcidin expression. This down-regulation of hepcidin in vivo implies
      that disturbed iron sensing may contribute to the hepatosiderosis seen in
      alcoholic liver disease. Alcohol intake is also a major factor in expression of
      the hemochromatosis phenotype in patients homozygous for the C282Y mutation of
      the HFE gene. METHODS: To assess the effect of alcohol in mice with iron
      overload, alcohol was administered to mice with disrupted Hfe and IL-6 genes and
      Tfr2 mutant mice and their respective 129x1/SvJ, C57BL/6J, and AKR/J wild-type
      congenic strains. Iron absorption, serum iron levels, and hepcidin expression
      levels were then measured in these mice compared with water-treated control mice.
      RESULTS: Alcohol was shown to have a strain-specific effect in 129x1/SvJ mice,
      with treated 129x1/SvJ mice showing a significant increase in iron absorption,
      serum iron levels, and a corresponding decrease in hepcidin expression. C57BL/6J
      and AKR/J strain mice showed no effect from alcohol treatment. 129x1/SvJ mice
      heterozygous or homozygous for the Hfe knockout had a diminished response to
      alcohol. All 3 strains were shown to have high blood alcohol levels. CONCLUSIONS:
      The effect of alcohol on iron homeostasis is dependent on the genetic background
      in mice. In an alcohol-susceptible strain, mutation of the Hfe gene diminished
      the response of the measured iron indices to alcohol treatment. This indicates
      that either maximal suppression of hepcidin levels had already occurred as a
      result of the Hfe mutation or that Hfe was a component of the pathway utilized by
      EtOH in suppressing hepcidin production and increasing iron absorption.

PMID- 17207113
TI  - Ethanol self-administration and alterations in the livers of the cynomolgus
      monkey, Macaca fascicularis.
AB  - BACKGROUND: Most of the studies of alcoholic liver disease use models in which
      animals undergo involuntary administration of high amounts of ethanol and consume
      diets that are often high in polyunsaturated fatty acids. The objectives of this
      study were (1) to evaluate whether cynomolgus monkeys (Macaca fascicularis)
      drinking ethanol voluntarily and consuming a diet with moderate amounts of lipid
      would demonstrate any indices of alcoholic liver disease past the fatty liver
      stage and (2) to determine whether these alterations were accompanied by
      oxidative stress. METHODS: Six adult male and 6 adult female cynomolgus monkeys
      were allowed to consume ethanol voluntarily for 18 to 19 months. Additional
      monkeys were maintained on the same consumption protocol, but were not provided
      with ethanol. During the course of the study, liver biopsy samples were monitored
      for lipid deposition and inflammation, serum for levels of liver enzymes, and
      urine for concentrations of the isoprostane (IsoP) metabolite, 2,3-dinor-5,6
      dihydro-15-F(2t)-IsoP, a biomarker for oxidative stress. Liver mitochondria were
      monitored for respiratory control and liver for concentrations of neutral lipids,
      adenine nucleotides, esterified F(2) isoprostanes, oxidized proteins, 4
      hydroxynonenal (HNE)-protein adducts, and protein levels of cytochrome P-450 2E1
      and 3A4. RESULTS: Ethanol consumption ranged from 0.9 to 4.05 g/kg/d over the
      period of the study. Serum levels of aspartate amino transferase were elevated in
      heavy-consuming animals compared with those in ethanol-naive or moderate
      drinkers. Many of the ethanol consumers developed fatty liver and most showed
      loci of inflammation. Both hepatic energy charge and phosphorylation potential
      were decreased and NADH-linked respiration was slightly, but significantly
      depressed in coupled mitochondria as a result of heavy ethanol consumption. The
      urinary concentrations of 2,3-dinor-5,6-dihydro-15-F(2t)-IsoP increased as high
      as 33-fold over that observed in ethanol-abstinent animals. Liver cytochrome P
      450 2E1 concentrations increased in ethanol consumers, but there were no ethanol
      elicited increases in hepatic concentrations of the esterified F(2) isoprostanes,
      oxidized proteins, or HNE-protein adducts. CONCLUSION: Our studies show that
      cynomolgus monkeys undergoing voluntary ethanol consumption for 1.5 years exhibit
      many of the features observed in the early stages of human alcoholic liver
      disease. Ethanol-elicited fatty liver, inflammation, and elevated serum aspartate
      amino transferase were evident with a diet that contained modest amounts of
      polyunsaturated lipids. The dramatic increases in urinary IsoP demonstrated that
      the animals were being subjected to significant oxidative stress that correlated
      with their level of ethanol consumption.

PMID- 17207114
TI  - Reduced frontal lobe activity in subjects with high impulsivity and alcoholism.
AB  - OBJECTIVE: Impulsivity is an important characteristic of many psychiatric
      disorders, including substance-related disorders. These disinhibitory disorders
      have a similar underlying genetic diathesis, with each disorder representing a
      different expression of the same underlying genetic liability. This study
      assessed whether there is a relationship between impulsivity and alcohol
      dependence, and their correlations with P3 (P300) amplitude, a proposed
      endophenotype of alcoholism. METHODS: Healthy control subjects (n=58) and
      subjects with DSM-IV diagnosis of alcohol dependence (n=57) were assessed with a
      visual oddball task. Event-Related Potentials (ERPs) were recorded from 61 scalp
      electrodes and P3 amplitudes measured. Barratt Impulsiveness Scale (BIS), version
      11, was used to evaluate impulsivity. Source localization of P3 was computed
      using low-resolution brain electromagnetic tomography (LORETA). RESULTS:
      Alcoholic subjects manifested reductions in target P3 amplitudes (p<0.0001).
      Using LORETA, significantly reduced activation was mapped in the cingulate,
      medial, and superior frontal regions in alcoholic subjects and highly impulsive
      subjects. Alcoholic subjects had significantly higher scores on the BIS
      (p<0.0001) than nonalcoholic individuals. There were significant negative
      correlations between total scores on BIS and P3 amplitude (r=-0.274, p=0.003, on
      Pz; r=-0.250, p=0.007, on Cz). CONCLUSIONS: Our results demonstrate a strong
      frontal focus of reduced activation during processing of visual targets in
      alcoholic subjects and individuals with higher impulsivity. The findings suggest
      that impulsivity may be an important factor that underlies the pathogenesis of
      alcohol dependence. Studies are underway to examine the relationship between
      impulsivity and ERPs in offspring of alcoholic subjects, and to identify genes
      associated with the underlying predisposition involved in disinhibitory
      disorders.

PMID- 17207115
TI  - Working with the alcohol industry on alcohol policy: should we sometimes sit at
      the same table?

PMID- 17207116
TI  - The need for dynamic drug policy.

PMID- 17207117
TI  - Alcohol and other drug use and the transition from riding to driving.

PMID- 17207118
TI  - Slovenia: alcohol today--could a country be addicted to alcohol?

PMID- 17207119
TI  - The Journal of Inebriety (1876-1914): history, topical analysis, and photographic
      images.
AB  - AIMS: The publication of the Journal of Inebriety (1876-1914) chronicled the rise
      and fall of the first era of organized addiction medicine in the United States.
      METHODS: Findings from historical research, a content analysis of the Journal's
      35 volumes and 141 issues and images from the Journal illustrate visually the
      medical treatment of addiction in the United States in the late 19th and early
      20th centuries. RESULTS: Under the editorial direction of Dr T. D. Crothers, the
      Journal of Inebriety published papers and reviews focused primarily on the
      medical treatment of alcohol and opiate addiction within a growing international
      network of inebriate homes and asylums. CONCLUSIONS: The history of the Journal
      of Inebriety mirrors efforts in America to forge a legitimized field of addiction
      medicine amid conflicting conceptualizations of the nature of severe alcohol and
      other drug problems.

PMID- 17207120
TI  - Risk assessment of ritual use of oral dimethyltryptamine (DMT) and harmala
      alkaloids.
AB  - AIM: To extend previous reviews by assessing the acute systemic toxicity and
      psychological hazards of a dimethyltryptamine and beta-carboline brew
      (ayahuasca/hoasca) used in religious ceremonies. METHOD: A systematic literature
      search, supplemented by interviews with ceremony participants. RESULTS: No
      laboratory animal models were located that tested the acute toxicity or the abuse
      potential of ayahuasca. Separate animal studies of the median lethal dose of
      dimethyltryptamine (DMT) and of several harmala alkaloids indicated that a lethal
      dose of these substances in humans is probably greater than 20 times the typical
      ceremonial dose. Adverse health effects may occur from casual use of ayahuasca,
      particularly when serotonergic substances are used in conjunction. DMT is capable
      of inducing aversive psychological reactions or transient psychotic episodes that
      resolve spontaneously in a few hours. There was no evidence that ayahuasca has
      substantial or persistent abuse potential. Long-term psychological benefits have
      been documented when ayahuasca is used in a well-established social context.
      CONCLUSION: A decoction of DMT and harmala alkaloids used in religious ceremonies
      has a safety margin comparable to codeine, mescaline or methadone. The dependence
      potential of oral DMT and the risk of sustained psychological disturbance are
      minimal.

PMID- 17207121
TI  - The reliability and validity of the Severity of Dependence Scale for detecting
      cannabis dependence in psychosis.
AB  - AIMS: To determine the reliability and validity of the Severity of Dependence
      Scale (SDS) for detecting cannabis dependence in a large sample of in-patients
      with a schizophrenia spectrum disorder. DESIGN: Cross-sectional study.
      PARTICIPANTS: Participants were 153 in-patients with a schizophrenia spectrum
      disorder in Brisbane, Australia. MEASUREMENTS: Participants were administered the
      SDS for cannabis dependence in the past 12 months. The presence of Diagnostic and
      Statistical Manual Version-IV (DSM-IV) cannabis dependence in the previous 12
      months was assessed using the Comprehensive International Diagnostic Interview
      (CIDI). FINDINGS: The SDS had high levels of internal consistency and strong
      construct and concurrent validity. Individuals with a score of >or = 2 on the SDS
      were nearly 30 times more likely to have DSM-IV cannabis dependence. The SDS was
      the strongest predictor of DSM-IV cannabis dependence after controlling for other
      predictor variables. CONCLUSIONS: The SDS is a brief, valid and reliable screen
      for cannabis dependence among people with psychosis.

PMID- 17207122
TI  - Does subtle screening for substance abuse work? A review of the Substance Abuse
      Subtle Screening Inventory (SASSI).
AB  - AIM: Through a complex combination of direct (face-valid) and indirect (subtle)
      subscales, the Substance Abuse Subtle Screening Inventory (SASSI) is purported to
      detect substance use disorders with a high degree of validity regardless of
      respondent honesty or motivation. This review evaluates empirical evidence
      regarding the reliability and validity of this widely used screening instrument.
      METHODS: Source documents were 36 peer-reviewed reports yielding data regarding
      the SASSI's internal consistency, test-retest reliability, psychometric
      structure, convergent and divergent validity and criterion (predictive) validity.
      RESULTS: The total N of the studies reviewed equaled 22 110. Internal consistency
      is high for the overall SASSI and for its direct but not its indirect (subtle)
      subscales, suggesting that the instrument taps a single face-valid construct.
      SASSI classifications converged with those from other direct screening
      instruments, and were also correlated with ethnicity, general distress and social
      deviance. Studies found test-retest reliability lower than that reported in the
      test manuals. Sensitivity was found to be similar to that for public domain
      screening instruments, but on specificity the SASSI appears to yield a high rate
      of false positives. CONCLUSION: No empirical evidence was found for the SASSI's
      claimed unique advantage in detecting substance use disorders through its
      indirect (subtle) scales to circumvent respondent denial or dishonesty.
      Recommendations for screening and for future research with the SASSI are offered.

PMID- 17207123
TI  - Adolescent passengers of drunk drivers: a multi-level exploration into the
      inequities of risk and safety.
AB  - AIMS: This study determined the individual-, neighbourhood- and provincial-level
      effects of rural residence, socio-economic status (SES), substance use and
      driving behaviours on adolescents' riding with a drunk driver (RDD). DESIGN:
      Multi-level study based on cross-sectional self-reported anonymous data from the
      Student Drug Use Survey in the Atlantic Provinces (SDUSAP) and Census Canada
      data, merged on the postal code of participating schools. The sample design of
      the SDUSAP was a single-stage cluster sample of randomly selected classes
      stratified by grade and region. SETTING: The Atlantic provinces of Canada.
      PARTICIPANTS: A total of 12 990 students in junior and senior high schools, with
      an average age of 15 years, participated in the 2002 SDUSAP. MEASUREMENTS: The
      outcome variable was past-year RDD. The main individual-level independent
      variables were SES, rural residence, substance use and driving behaviours. The
      school-neighbourhood independent variables were the prevalence of heavy episodic
      drinking, driving under the influence of alcohol, driver's licence, highest level
      of educational attainment and low income. FINDINGS: The prevalence of RDD was
      23.3% in 2002. Among students in grades 9-12, lower family SES, rural residence,
      substance use and driving under the influence were found to be independent
      individual-level risk factors for RDD; having a driver's licence was found to be
      protective. At the provincial and school-neighbourhood levels, a high prevalence
      of driving under the influence of alcohol and low educational attainment were
      found to be independent risk factors for RDD after taking into account individual
      characteristics. CONCLUSIONS: This study provides evidence that inequities exist
      in the options for adolescents to be ensured of passenger safety, and that
      interventions aimed at decreasing the extent to which adolescents engage in
      riding with a drunk driver should be based on conceptual approaches that
      recognize ecological factors as well as individual-level susceptibility.

PMID- 17207124
TI  - Assessment may conceal therapeutic benefit: findings from a randomized controlled
      trial for hazardous drinking.
AB  - CONTEXT: The concept that assessment of a person's health status without
      subsequent intervention has beneficial effects in itself has stimulated much
      interest in underlying psychological mechanisms, methodological implications and
      its public health potential. There have, however, been few experimental studies
      of assessment effects. AIM: To test the hypothesis that assessment in itself
      produces a reduction in hazardous drinking. DESIGN AND SETTING: Two conditions
      (group A, leaflet only and group B, leaflet and assessment but no intervention)
      of a four-arm randomized controlled trial with enrollment in March-April 2003.
      PARTICIPANTS: A total of 975 students (17-29 years) attending a primary health
      care clinic completed a web-based Alcohol Use Disorders Identification Test
      (AUDIT) questionnaire. Of 599 who scored >or= 8576 consented to follow-up and
      were included in the full four-arm trial, of whom 293 (153 women) were assigned
      to groups A and B. INTERVENTION: Group A received an information leaflet at
      baseline. Group B received the information leaflet and 10 minutes of web-based
      assessment 4 weeks later. MEASUREMENTS: Drinking frequency, typical quantity,
      heavy episode frequency, personal problems and academic problems. FINDINGS:
      Baseline mean AUDIT scores were 15.0 (SD = 5.4) and 14.9 (SD = 5.0) in groups A
      and B, respectively. Twelve months after baseline, relative to group A, group B
      reported lower overall consumption (geometric means ratio 0.82, 95% CI: 0.68
      0.98), fewer heavy drinking episodes (0.66, 0.47-0.91), fewer problems (0.81,
      0.67-0.99) and lower AUDIT scores (beta = -1.63, -0.62 to -2.65). CONCLUSIONS:
      Brief assessment appeared to reduce hazardous drinking. Controlled trials that
      rely on assessment may therefore underestimate treatment effects. Limitations
      include the possibility of measurement artefact due to social desirability bias.

PMID- 17207125
TI  - A comparative multi-level analysis of contextual drinking in American and
      Canadian adults.
AB  - AIM: To investigate the effects of demographic factors and drinking location on
      contextual drinking in a comparison of US and Canadian adults. DESIGN: Multi
      level techniques were used to model the two-level hierarchical structure of
      drinking contexts (level 1) nested within individuals (level 2). PARTICIPANTS:
      Two random samples of current drinkers aged 18 years or older were drawn from
      Canada's Alcohol and Other Drugs Survey (CADS, 1994) and the 1995 National
      Alcohol Survey (NAS 9). The US sample included 2304 respondents (level 2) who
      reported a total of 5956 drinking contexts (level 1); in Canada, 5394 respondents
      reported 13 235 drinking contexts. MEASUREMENTS: Participants reported usual
      alcohol intake in up to four drinking locations. Demographic data included age,
      gender, education level, income and marital status. FINDINGS: Significant
      variation in usual alcohol intake was observed between drinking locations in both
      the US and Canada. The full multi-level models explained 25% of the variance at
      the contextual level and 25% and 22% at the individual level in the US and
      Canada. Contextual drinking was determined by a complex relationship between
      demographic characteristics and drinking locations. Some interactions between
      locations and demographic variables were observed for both the US and Canada,
      whereas others were observed only in the US sample. CONCLUSIONS: There is a need,
      from a population health perspective, for a multi-level approach in epidemiology
      and prevention that considers drinking setting as a relevant level for analysis
      and intervention.

PMID- 17207126
TI  - The effect of assertive continuing care on continuing care linkage, adherence and
      abstinence following residential treatment for adolescents with substance use
      disorders.
AB  - AIMS: This study compared assertive continuing care (ACC) to usual continuing
      care (UCC) on linkage, retention and a measure of continuing care adherence.
      Outcome analyses tested the direct and indirect effects of both conditions and
      level of adherence on early (months 1-3) and longer-term (months 4-9) abstinence.
      DESIGN: Two-group randomized design. SETTING: Eleven counties surrounding a
      community-based residential treatment program in the Midwestern section of the
      United States. PARTICIPANTS: A total of 183 adolescents, ages 12-17 years, with
      one or more Diagnostic and Statistical Manual version IV (DSM-IV) substance use
      dependence disorder and met American Society for Addiction Medicine (ASAM)
      placement criteria for non-medical residential treatment. INTERVENTION: Prior to
      discharge from residential treatment, participants were assigned randomly to
      receive either UCC, available at outpatient clinics in the 11-county study area,
      or ACC via home visits. MEASUREMENTS: Self-reported interview data were collected
      at intake, 3, 6 and 9 months post-residential discharge. Urine test data and
      interviews with a caregiver were conducted at baseline and 3 months. FINDINGS:
      ACC led to significantly greater continuing care linkage and retention and longer
      term abstinence from marijuana. ACC resulted in significantly better adherence to
      continuing care criteria which, in turn, predicted superior early abstinence.
      Superior early abstinence outcomes for both conditions predicted longer-term
      abstinence. CONCLUSIONS: ACC appears to be an effective alternative to UCC for
      linking, retaining and increasing adherence to continuing care. Replication with
      larger samples is needed to investigate further the direct and indirect effects
      of ACC found in this study

PMID- 17207127
TI  - A latent class analysis of illicit drug abuse/dependence: results from the
      National Epidemiological Survey on Alcohol and Related Conditions.
AB  - AIMS: We examine the co-occurrence of abuse/dependence across different illicit
      drugs and test associations between these classes and major psychiatric
      disorders. METHOD: Latent class analyses were used to characterize polysubstance
      abuse/dependence (AB/D) in 43 093 individuals who participated in the National
      Epidemiological Survey on Alcohol and Related Conditions. Multinomial logistic
      regression was performed to examine the association between the classes of life
      time illicit drug AB/D and gender, age and race, as well as life-time Diagnostic
      and Statistical Manual version IV (DSM-IV) alcohol abuse/dependence, nicotine
      dependence, major depressive disorder, generalized anxiety disorder, panic
      disorder, social phobia and antisocial personality disorder. RESULTS: Five latent
      classes were identified: no AB/D (class 1: 92.5%), cannabis AB/D only (class 2:
      5.8%), stimulants + hallucinogen AB/D (class 3: 0.6%), prescription drug AB/D
      (class 4: 0.6%) and polysubstance AB/D (class 5: 0.5%). Major depressive disorder
      and nicotine dependence were associated most strongly with class 5. Anxiety
      disorders were associated strongly with the prescription drug AB/D class while
      alcohol AB/D and ASPD were associated with classes 2, 3, 4 and 5 when compared to
      the reference class (class 1). CONCLUSIONS: Significant heterogeneity exists in
      this US population for polysubstance AB/D patterns with evidence for a subgroup
      with high rates of sedative, tranquilizer and opiate AB/D and a history of
      anxiety disorders, a stimulant/hallucinogens group, a high-risk group with
      elevated rates of all psychiatric disorders and a milder cannabis AB/D only
      group. Replication of such classes across other samples has significant
      implications, such as characterizing risk groups that may be etiologically
      diverse.

PMID- 17207128
TI  - Eating disorders and substance abuse in Canadian women: a national study.
AB  - AIMS: This study aimed to examine the comorbidity between eating disorders and
      substance use in a large nationally representative sample of Canadian adult
      women. Recent as well as life-time measures of substance use were used. DESIGN:
      The research was based on secondary analyses of data collected, using multi-stage
      stratified probability sampling, by Statistics Canada in the Mental Health and
      Well-being cycle 1.2 of the Canadian Community Health Survey (CCHS).
      MEASUREMENTS: The Eating Attitude Test (EAT-26) was used to measure risk of
      eating disorders. Alcohol use, dependence and interference, and illicit drug use,
      dependence and interference were measured using relevant modules from the short
      form of the Composite International Diagnostic Interview (CIDI-SF). PARTICIPANTS:
      Data on a nationally representative sample of Canadian adult women, grouped into
      three age groups, were used for this research. FINDINGS: Alcohol dependence and
      alcohol interference were associated significantly with the risk for an eating
      disorder in the three adult age groups. Significant associations were also found
      in the three age groups between risk for an eating disorder and the life-time
      abuse of and dependence on illicit drugs. Significant associations were found in
      the 15-24 and 25-44-year age groups when the 12-month time-frame was used.
      CONCLUSIONS: The study findings support the call for the development of short
      screening instruments for adult women with eating disorders and substance abuse,
      as well as for the development of treatment strategies that address the co
      occurrence of eating disorders and substance use

PMID- 17207129
TI  - Could the CARE-SHAKTI intervention for injecting drug users be maintaining the
      low HIV prevalence in Dhaka, Bangladesh?
AB  - AIMS: To explore whether the low HIV prevalence observed in Bangladesh results
      from prevention activities, this study uses mathematical modelling to estimate
      the impact of a needle/syringe exchange intervention for injecting drug users
      (IDUs) in Dhaka, Bangladesh. DESIGN: Epidemiological, behavioural and
      intervention monitoring data were used to parameterize a dynamic mathematical
      model, and fit it to National HIV Sero-surveillance data among IDUs (2000-02).
      The model was used to estimate the impact of the intervention on HIV transmission
      among IDUs and their sexual partners. SETTING: Dhaka, Bangladesh, where the HIV
      prevalence has remained low despite high-risk sexual and injecting behaviours,
      and growing HIV epidemics in neighbouring countries. FINDINGS: The model predicts
      that the intervention may have reduced the incidence of HIV among IDUs by 90%
      (95% CI 74-94%), resulting in an IDU HIV prevalence of 10% (95% CI 4-19%) after 8
      years of intervention activity instead of 42% (95% CI 30-47%) if the intervention
      had not occurred. CONCLUSIONS: The analysis highlights the potential for rapid
      HIV spread among IDUs in Dhaka, and suggests that the intervention may have
      substantially reduced IDU HIV transmission. However, there is no room for
      complacency. Sustained and expanded funding for interventions in Dhaka and other
      regions of Bangladesh are crucial to maintaining the low HIV prevalence.

PMID- 17207130
TI  - Psychological symptoms and physical health and health behaviours in adolescents:
      a prospective 2-year study in East London.
AB  - AIMS: To examine whether physical health and health-risk behaviours in young
      people are risk factors for psychological distress and depressive symptoms over a
      2-year period. DESIGN/SETTING: A 2-year, prospective epidemiological cohort study
      in East London. PARTICIPANTS: A total of 1615 adolescents from the Research with
      East London Adolescents: Community Health Survey (RELACHS)-a representative
      cohort of young people aged 11-12 and 13-14 years at baseline, followed-up after
      2 years. MEASUREMENTS: Psychological distress and depressive symptoms identified
      by the self-report Strengths and Difficulties Questionnaire and the Short Moods
      and Feelings Questionnaire at baseline and follow-up. Data on overweight/obesity,
      general health, long-standing illness, physical activity, smoking, alcohol use
      and drug use were collected from questionnaires completed by the adolescents at
      baseline and follow-up. FINDINGS: At follow-up, 10.1% of males and 12.9% of
      females reported psychological distress; 20% of males and 33.7% of females
      reported depressive symptoms. Having tried drugs or engaged in two or more health
      risk behaviours (smoking, alcohol use or drug use) at baseline predicted
      psychological distress and depressive symptoms at follow-up. Smoking on its own,
      long-standing illness, obesity/overweight and activity levels were not associated
      with later psychological health. Risk of poor psychological health at follow-up
      was associated strongly with psychological health at baseline. CONCLUSIONS:
      Psychological health at baseline was the strongest predictor of psychological
      health at follow-up. Engaging in two or more health-risk behaviours moderately
      increased the risk of poor psychological health, suggesting that prevention
      strategies targeting co-occuring substance use may reduce burden of disease.

PMID- 17207131
TI  - The role of sensory perception in the development and targeting of tobacco
      products.
AB  - AIMS: To examine tobacco industry research on smoking-related sensory effects,
      including differences in sensory perception across smoker groups, and to
      determine whether this research informed targeted product development and
      impacted the development of commercial tobacco products. DESIGN: We searched
      previously secret internal tobacco industry documents available online through
      document databases housed at Tobacco Documents Online, the British American
      Tobacco Document Archive and the Legacy Tobacco Documents Library. We identified
      relevant documents using a snowball sampling method to first search the databases
      using an initial set of key words and to then establish further search terms.
      FINDINGS: Sensory research is a priority within the tobacco industry directly
      impacting commercial markets both in the United States and internationally.
      Sensory factors contribute to smoker satisfaction and product acceptance, and
      play an important role in controlling puffing behavior. Cigarette manufacturers
      have capitalized on distinct sensory preferences across gender, age and ethnic
      groups by tailoring products for specific populations. CONCLUSIONS: Regulation of
      tobacco products is needed to address product changes that are used to reinforce
      or contribute to tobacco dependence; for instance, the incorporation of additives
      that target attributes such as smoothness, harshness and aftertaste. Greater
      understanding of the role of sensory effects on smoking behavior may also help to
      inform the development of tobacco treatment options that support long-term
      tobacco abstinence.

PMID- 17207132
TI  - Effectiveness of a smoking cessation intervention in older adults.
AB  - AIMS: To: (a) identify characteristics of older smokers considering cessation of
      smoking; (b) evaluate a cessation intervention plus access to nicotine
      replacement therapy (NRT); (c) identify predictors of those who successfully
      quit; and (d) evaluate the effectiveness of the intervention in those AGED >or =
      75 years. DESIGN: Self-selection of: (a) a cessation of smoking programme; or (b)
      ongoing smoking. SETTING: Teaching hospital, Perth, Western Australia.
      PARTICIPANTS: A larger study recruited smokers and never smokers: from this the
      215 community-dwelling smokers (>or= 5 cigarettes/day) aged >or= 68 years (171
      males) were enrolled. INTERVENTION: Brief intervention with telephone support and
      access to NRT versus no intervention. MEASUREMENTS: (a) Profile of older adults
      planning to quit smoking compared with continuing smokers; (b) cessation at 6
      months defined as 30-day point prevalence validated via expired carbon monoxide;
      and (c) factors predictive of successful cessation. FINDINGS: There were 165
      intervention participants. Compared with the 50 continuing smokers, participants
      in the intervention were younger and had significantly less years of regular
      smoking, more previous quit attempts and greater nicotine dependence scores. At 6
      months, the point prevalence of ex-smokers was 25% (n = 42) with 20% (n = 33)
      being abstinent throughout the study. No continuing smoker had ceased smoking.
      Among the intervention group, logistic regression showed that those who used NRT
      (OR 4.36), were male (OR 3.17), had higher anxiety (OR 1.67) or rejected 'more
      colds and coughs' as a reason for quitting (OR 2.91) were more likely to be
      successful quitters. Of those aged >or= 75 years (n = 77), 25% matched cessation
      criteria. CONCLUSIONS: Older smokers can be engaged successfully in a brief
      intervention plus NRT as aids to cessation of smoking. The intervention was also
      effective in the older subgroup of participants. Social factors may provide an
      additional means of motivating older smokers to quit.

PMID- 17207133
TI  - UK smokers' and ex-smokers' reactions to cigarettes promising reduced risk.
AB  - AIMS: This study evaluated the impact of exposure to information about a novel
      cigarette claiming to reduce exposure to tobacco toxins ('potential reduced
      exposure product' cigarette or PREP-C) on smokers' and ex-smokers' perceptions of
      PREP-C, on quit interest among smokers and on interest in resuming smoking among
      ex-smokers. DESIGN AND PARTICIPANTS: A random digit-dialed telephone survey was
      conducted in the United Kingdom with 500 current smokers and 106 ex-smokers who
      had quit within the last 2 years. INTERVENTION: The interviewer described a novel
      cigarette that claimed to significantly reduce exposure to smoke toxins.
      MEASUREMENTS: Respondents' interest in purchasing the PREP-C, beliefs about its
      safety and risk reduction and smokers' quit interest, as measured by stage of
      change, before and after exposure to PREP-C information. FINDINGS: Among smokers,
      76.5% were interested in purchasing PREP-C; interest did not vary by stage of
      change. Almost all smokers (90.6%) thought PREP-C was safer than regular
      cigarettes, with 5.4% indicating that the health risks were equivalent to not
      smoking at all. Exposure to PREP-C description did not change quit interest.
      Among ex-smokers, 5.6% believed PREP-C carried no health risk and 7.1% expressed
      purchase interest. CONCLUSIONS: Smokers and ex-smokers interpreted claims of
      reduced toxin exposure as reduced health risk and responded positively towards
      PREP-Cs. With the increasing introduction of PREP-Cs world-wide, evaluation of
      these products and their claims on quitting among smokers and on relapse among ex
      smokers is a matter of public health urgency.

PMID- 17207134
TI  - Health exchange and prevention of HIV: the evidence for effectiveness is beyond
      dispute.

PMID- 17207142
TI  - 'Non-specific effects of vaccines'--an important analytical insight, and call for
      a workshop.

PMID- 17207143
TI  - Survival bias in observational studies of the impact of routine immunizations on
      childhood survival.
AB  - OBJECTIVES: In situations with vaccination coverage high enough to control
      pertussis, observational studies have reported divergent effects of diphtheria
      tetanus-pertussis (DTP) vaccination on childhood survival. We examined whether
      this could be because of methodological differences. METHODS: Some studies of the
      impact of DTP updated information on vaccination retrospectively (retrospective
      updating approach) while others kept vaccination status fixed for the time
      between follow-up visits (landmark approach). First, we conducted simulations
      with these approaches to investigate the impact of different mortality levels,
      vaccination incidence rates, intervals between data collection visits, and the
      proportion of children whose vaccination card had not been seen after death.
      Second, we re-analysed data from Guinea-Bissau using the retrospective updating
      approach. RESULTS: In simulations, the retrospective updating approach produced
      rate ratio (vaccinated/unvaccinated) estimates biased towards zero because of a
      differential misclassification which created survival bias as risk-free
      observation time was allocated to the vaccinated group. The landmark approach
      produced rate ratio estimates biased towards one. Biases increased with interval
      between data collection visits and incidence of vaccination, but were unaffected
      by the underlying mortality level. Survival bias increased with the proportion of
      dead children whose vaccination status could not be updated. The re-analysis of
      data from Guinea-Bissau changed the estimated impact of DTP from an 84% higher
      mortality using the landmark approach to a 37% lower mortality using the
      retrospective updating approach. CONCLUSIONS: The apparent contradiction between
      DTP studies could be because of methodological differences. To assess child
      survival associated with routine vaccinations, studies minimizing the effect of
      biases are warranted.

PMID- 17207144
TI  - DTP vaccination and child survival in observational studies with incomplete
      vaccination data.
AB  - BACKGROUND: Observational studies of diphtheria-tetanus-pertussis (DTP) vaccine
      from longitudinal study sites have reported divergent effects on child survival,
      ranging from 10-fold reduction to threefold increased mortality. None of these
      studies had complete information on DTP vaccinations from both survivors and
      children who died. We reviewed the data analysis methodology to assess whether
      methodological differences could explain the divergent results. DESIGN: Studies
      have used case-control design, survival analysis with interval-fixed vaccination
      status (landmark approach), and survival analysis with retrospective updating of
      vaccination status. RESULTS: Seven studies using a case-control design or a
      landmark approach found a negative effect of DTP on child survival. Eight of nine
      survival analyses with retrospective updating of vaccination status reported a
      beneficial effect. This beneficial effect of DTP increased with the length of the
      interval between data collection visits. Studies with long interval between
      visits had very high mortality rates among unvaccinated children, low mortality
      rate ratios for vaccinated compared with unvaccinated children, and strongly
      beneficial estimates of DTP. CONCLUSION: The divergent results in observational
      studies of the impact of DTP on child survival are partly because of
      methodological differences. To assess the impact on mortality of routine
      vaccinations, observational study designs which minimize the effect of bias are
      warranted. Randomized trials should be considered.

PMID- 17207145
TI  - Trial participation and vaccine desirability for Vi polysaccharide typhoid fever
      vaccine in Hue City, Viet Nam.
AB  - OBJECTIVES: To identify demand for Vi typhoid fever vaccine for school-age
      children; obstacles and enabling factors for vaccine delivery; and socio
      behavioural factors associated with trial participation and possible predictors
      of future vaccine acceptance, in Hue City, Viet Nam. METHODS: Pre- and post-trial
      surveys of randomly selected households with children aged 6-17 years. Simple
      multinomial logistic analyses for ratios of relative risks (RRR) and significance
      on trial participation by demographics and variables related to typhoid fever,
      vaccination, and pre-trial experiences with information and consents. Multiple
      logistic regressions to assess differences in participation based on child's
      characteristics. RESULTS: As many as 62.6% of households let all school age
      children participate, 10.2% let some participate, and 26.8% let none of their
      children participate in the trial. Factors associated with all children
      participating included past use of healthcare facilities (RRR, 0.45; 95% CI, 0.24
      0.83), knowledge of vaccines (RRR, 0.17; 95% CI, 0.03-0.86), and perceived causes
      of typhoid fever (RRR, 0.90; 95% CI, 0.81-0.99). Factors associated with some
      children participating included utilization of healthcare facilities (RRR, 0.08;
      95% CI, 0.01-0.66) and perceived severity of typhoid fever (RRR, 0.64; 95% CI
      0.46-0.88). Participation was associated with satisfaction regarding pre
      vaccination information and consent procedures. Children and adolescents were
      active decision-makers. Only 14 of 461 (2.2%) respondents would not use the Vi
      vaccine in the future for their child(ren). CONCLUSIONS: Inter-related factors
      contribute to participation in a clinical vaccine trial, which may differ from
      desire to participate in a public health campaign. Educational campaigns need to
      be targeted to children and adolescents, and consideration for assent procedures
      for minors. Obtaining informed consent may affect trial participation within a
      social and political system unaccustomed to these procedures.

PMID- 17207146
TI  - Safety and immunogenicity of the RTS,S/AS02A candidate malaria vaccine in
      children aged 1-4 in Mozambique.
AB  - BACKGROUND: The development of a malaria vaccine remains a public health priority
      for sub-Saharan Africa. RTS,S/AS02A candidate malaria vaccine has been shown to
      be safe and immunogenic in previous studies in adults and staggered dose
      escalation studies in children in The Gambia. However, genetic features and the
      intensity of malaria transmission may modify the safety and immune response of a
      vaccine. OBJECTIVE: We carried out a phase I, double-blind randomized controlled
      trial in 60 children aged 1-4 in Mozambique to evaluate the safety,
      reactogenicity and immunogenicity of the paediatric vaccine dose (fixed 25 microg
      RTS,S in 0.25 ml) of RTS,S/AS02A, prior to undertaking a planned larger phase IIb
      proof-of-concept of efficacy study in the same population. METHOD: Children were
      randomized to receive either RTS,S/AS02A or Engerix-B vaccine. Monitoring of
      safety and reactogenicity included detailed clinical and laboratory analyses and
      assessment of adverse events (AEs). RESULTS: The RTS,S/AS02A was found to be safe
      and well tolerated. Serious adverse events were balanced between both groups and
      none was related to vaccination. The frequency of adverse events reported with
      RTS, S/AS02A was comparable to previous studies in children. Grade 3 AEs were
      infrequent (one case of pain, one of fever in each group and some swelling
      greater than 20 mm in diameter), transient and resolved without sequelae.
      RTS,S/AS02A was highly immunogenic for anti-circumsporozoite protein antibody
      response and induced a strong anti-hepatitis-B surface antigen response.

PMID- 17207147
TI  - Rapid diagnostic tests for dengue and leptospirosis: antibody detection is
      insensitive at presentation.
AB  - OBJECTIVE: To determine the performance of rapid diagnostic tests for dengue and
      leptospirosis that rely on detecting antibodies that may not be produced when
      patients present for medical treatment. METHODS: We prospectively enrolled 723
      patients with undifferentiated febrile illness presenting to rural hospitals in
      northern and northeastern Thailand over a 1-year period. We evaluated rapid
      antibody detection diagnostic tests for dengue and leptospirosis on these
      patients. RESULTS: Sensitivity of the tests was low at the acute visit (7.6
      21.5%). Sensitivity at the convalescent visit ranged from 25.8% to 81.5% and was
      significantly higher than at the acute visit for all tests (chi(2), P < 0.001).
      CONCLUSIONS: Low sensitivity of the rapid tests at presentation suggests that
      their utility in the acute phase of dengue and leptospirosis is limited.

PMID- 17207148
TI  - Assessing health worker performance in malaria case management of underfives at
      health facilities in a rural Tanzanian district.
AB  - OBJECTIVE: To study the quality of malaria case management of underfives at
      health facilities in a rural district, 2 years after the Tanzanian malaria
      treatment policy change in 2001. METHODS: Consultations of 117 sick underfives by
      12 health workers at 8 health facilities in Mkuranga District, Tanzania were
      observed using checklists for history taking, counselling and prescription.
      Diagnoses and treatment were recorded. Exit interviews were performed with all
      mothers/guardians and blood samples taken from the underfives for the detection
      of malaria parasites and antimalarial drugs. Quality of care was measured using
      indicators adopted from the integrated management of childhood illnesses multi
      country evaluation. RESULTS: Quality of care measured by indicator scores
      averaged 31% of what was considered optimal. The poorest results were for history
      taking. Nevertheless, 89% of febrile children were treated with antimalarials, in
      line with national guidelines for fever treatment. Of these, 61% had a
      parasitaemia > or =2000/microl. There was no difference in treatment given to
      those with parasitological malaria compared with those without parasites. Pre
      treatment levels of chloroquine and sulphadoxine/pyrimethamine were low and
      detected in 2% and 13%, respectively. CONCLUSION: Although most febrile children
      were given antimalarial treatment, quality of care in terms of history taking and
      counselling was sub-optimal. Despite this, the study community had changed
      behaviour from self-treatment to seeking care at health facilities. This is
      encouraging for introduction of artemisinin-based combination therapies policies
      as one could focus resources into improving care at health facilities and still
      reach out with treatment to most febrile children.

PMID- 17207149
TI  - Seasonal variations in maternal mortality in Maputo, Mozambique: the role of
      malaria.
AB  - OBJECTIVE: To evaluate the impact of malaria on maternal death through the
      analysis of the seasonal variations of crude and malaria-specific maternal
      mortality rates. METHODS: All maternal deaths and live births occurring at Maputo
      Central Hospital, located in an urban area, between January 2001 and December
      2003, were retrospectively recorded. Clinical diagnoses of the causes of death
      and period of the year were analysed. RESULTS: Two hundred and seventy-eight
      deaths were recorded. The overall crude maternal mortality rate was 995/100 000
      live births. Malaria was the most frequent cause of maternal death, accounting
      for 23%. Crude and malaria-specific maternal mortality rates showed a similar
      pattern of seasonal variation, with peaks at the beginning and the end of the
      malaria transmission season. The malaria-specific maternal mortality rate was
      significantly higher during the rainy seasons (rate ratio 1.919; 95% CI 1.061,
      3.470; P = 0.031). CONCLUSIONS: Malaria may contribute to maternal mortality in
      highly endemic countries in sub-Saharan Africa, at least in urban areas. Efforts
      to improve malaria control in pregnancy may have an impact on maternal mortality
      in sub-Saharan Africa.

PMID- 17207150
TI  - Quality control of active ingredients in artemisinin-derivative antimalarials
      within Kenya and DR Congo.
AB  - OBJECTIVES: Artemisinin-derivative drugs are widely used to treat Plasmodium
      falciparum malaria and very few studies have investigated the quality of these
      medicines in Africa. We analysed the active ingredient contents of artemisinin
      derivative drugs marketed in Kenya and DR Congo. METHODS: We analysed tablets,
      capsules, dry suspensions and injections (IM) containing either artemether (AM),
      arteether (AE), artesunate (ARS) or dihydroartemisinin (DHA). The content of
      active ingredients and preservatives was determined quantitatively using
      validated HPLC-UV methods. All analyses were done according to European
      pharmacopoeia requirements. RESULTS: Labelled active ingredients were identified
      in all samples, however with varying dosages. Nine of the 24 drug samples
      analysed did not comply with the pharmacopoeial requirements of 95-105%: seven
      samples were underdosed and two were slightly overdosed. DHA was the active
      ingredient in 57% of the underdosed samples. AE injections had the lowest drug
      content (77%). Two-thirds of the dry powder suspensions were either substandard
      or fake. Tablets were up to 23% out of range. Unidentified peaks were observed on
      the chromatograms of AE IM injections and a DHA dry powder. CONCLUSIONS:
      Counterfeit or substandard artemisinin-derivative drugs are being sold in parts
      of Africa, presenting a potential route for resistance development in the future.
      Appropriate measures need to be taken to maintain proper and safe use of these
      medicines.

PMID- 17207151
TI  - A model to simulate the impact of timing, coverage and transmission intensity on
      the effectiveness of indoor residual spraying (IRS) for malaria control.
AB  - OBJECTIVE: (i) To develop a temperature- and rainfall-driven model of malaria
      transmission capable of prediction. (ii) To use the model to examine the
      relationship between the intervention timing and transmission intensity on the
      effectiveness of indoor residual spraying (IRS). METHODS: A dynamic model of
      malaria transmission was developed from existing models of malaria transmission
      dynamics. The model was used to retrospectively predict actual malaria cases from
      Hwange district in Zimbabwe using actual meteorological and IRS timing and
      coverage data. Simulations of alternative intervention scenarios (timing and
      coverage) examined the effectiveness of earlier and later interventions, at
      higher and lower coverage levels in epidemic and non-epidemic years. FINDINGS:
      The model was able to predict actual malaria cases in Hwange over a four-and-a
      half-year period with a lead time of 4 months (e.g. January rainfall and
      temperature predicts April malaria) and a correlation coefficient of 0.825 (r(2)
      = 0.6814). The IRS simulations show that the marginal benefits of increasing IRS
      coverage are higher in high-transmission (HT) years relative to lower
      transmission years. This implies that over a period of years, maximum impact
      could be achieved with a given quantity of insecticide by increasing coverage in
      HT years. However, the model also shows that earlier spraying is more effective
      in all years, especially so in epidemic years, and that IRS has limited impact if
      it is carried out too late in relation to peak transmission. CONCLUSION:
      Temperature- and rainfall-driven models of malaria transmission have the
      potential to predict malaria epidemics. Early intervention based on prior
      knowledge of the magnitude of the malaria season can be more effective and
      efficient than carrying out routine activities every year. Malaria control
      planners need improved access to the technology that would allow them to better
      predict malaria epidemics and develop Malaria Early Warning Systems (MEWS). MEWS
      can then be linked to intervention planning to reduce the devastating impact of
      malaria epidemics on populations.

PMID- 17207152
TI  - A stepwise approach to the laboratory diagnosis of Buruli ulcer disease.
AB  - OBJECTIVE: In view of technical and financial limitations in areas of endemicity,
      the current practice and recommendations for the laboratory diagnosis of Buruli
      ulcer disease (BUD) may have to be reconsidered. We reviewed diagnostic results
      in order to explore options for a modified, more practicable, cost-effective and
      timely approach to the laboratory diagnosis of BUD. METHODS: Diagnostic specimens
      from 161 clinically diagnosed BUD patients from four different treatment centres
      in Ghana were subjected to laboratory analysis. The positivity rates of the
      laboratory assays were compared. RESULTS: The number of laboratory-confirmed
      clinically diagnosed BUD cases with one positive confirmative test was 20% higher
      than that with two positive confirmative tests. The specificity of microscopy
      (MIC) and PCR was 96.6% and 100%, respectively. Subsequent analysis of specimens
      from surgically excised pre-ulcerative tissue-by-tissue MIC and tissue PCR
      rendered 65% laboratory-confirmed BUD cases. Subsequent analysis of diagnostic
      swabs from ulcerative lesions by swab smear MIC and swab PCR rendered 70% of
      laboratory-confirmed BUD cases. CONCLUSIONS: The specificity of the diagnostic
      tests used in this study suggests that one positive diagnostic test may be
      considered sufficient for the laboratory confirmation of BUD. Subsequent
      application of different diagnostic tests rendered a laboratory confirmation of
      65% pre-ulcerative and of 70% ulcerative lesions. Implementation of a stepwise,
      subsequent analysis of diagnostic specimens will result in considerable cost
      saving compared with simultaneous testing of specimens by several diagnostic
      assays.

PMID- 17207153
TI  - Adoption of safer infant feeding and postpartum sexual practices and their
      relationship to maternal HIV status and risk of acquiring HIV in Zimbabwe.
AB  - OBJECTIVE: To examine the relationships between maternal knowledge and concern
      about HIV status, adoption of preventive practices and risk of acquiring HIV in
      Zimbabwe. METHODS: Knowledge and behavioural data were collected via interview
      from 2595 mothers enrolled in ZVITAMBO, a randomized trial of postpartum vitamin
      A supplementation that also offered education on safer infant feeding and sexual
      practices. Mothers were tested for HIV at delivery; those uninfected at baseline
      were retested during study follow-up. Logistic regression methods were used to
      identify variables associated with adoption of preventive behaviours and, for HIV
      negative mothers, their relationship to risk of acquiring HIV post-delivery.
      RESULTS: A total of 518 mothers (20%) reported practicing safer sex and 289
      mothers (11%) reported modifying their feeding behaviour because of HIV. Fear of
      transmitting HIV (50.4%) and protecting the baby's health (30.9%) were the most
      frequently cited reasons for behaviour change. Forty-nine HIV-negative mothers
      acquired HIV during the first postpartum year. After taking into account other
      significant covariates, mothers who were concerned about their own HIV status
      were 1.9 times more likely (95% CI: 1.05-3.52; P = 0.03), and those reporting
      safer sex practices were 58% less likely to become infected (adjusted odds ratio:
      0.42; 95% CI: 0.17-1.04; P = 0.06). Married women who reported practicing
      abstinence to prevent HIV were 3.2 times more likely to become infected than non
      abstaining mothers (P = 0.01), while there were no new HIV infections among
      abstaining single mothers. CONCLUSIONS: Greater emphasis should be given to safer
      sex practices among women who test negative in mother-to-child HIV prevention
      programmes.

PMID- 17207154
TI  - Evaluation of immunodiagnostics for toxocarosis in experimental porcine
      cysticercosis.
AB  - We assessed whether immunodiagnostic tests for cysticercosis can cross-react with
      the currently available immunodiagnostic tests for Toxocara canis in an
      established animal model for cysticercosis infection in pigs, known host for
      Toxocara. We examined by TES-enzyme-linked immunosorbent test and immunoblot
      assay for toxocarosis and cysticercosis the baseline and final follow-up sera of
      10 pigs, before and after (3 months) infection with Taenia solium. After
      successful cysticercosis infection, the nine evaluable pigs became seropositive
      to T. solium (enzyme-linked immunoelectrotransfer blot assay), but did remain
      seronegative for Toxocara in both assays, documenting the lack of cross
      reactivity with anti-T. solium antibodies in both T. canis assays. These findings
      should help clinicians better interpret serology for toxocariosis and
      cysticercosis in endemic areas for both helminth infections.

PMID- 17207155
TI  - What role do coagulation disorders play in the pathogenesis of leptospirosis?
AB  - Leptospirosis is a zoonosis of worldwide distribution, spread by the urine of
      infected animals. It is a major public health problem, especially in developing
      countries, where circumstances for transmission are most favourable. The clinical
      picture varies from mild disease to a severe illness with haemostatic
      derangements and multiorgan failure eventually leading to death. Although the
      haemorrhagic complications of severe disease are serious, the pathophysiology is
      scarcely elucidated. The complex mechanisms involved in inflammation-induced
      coagulation activation are extensively studied in various infectious diseases,
      i.e. Gram-negative sepsis. Tissue factor-mediated coagulation activation,
      impairment of anticoagulant and fibrinolytic pathways in close concert with the
      cytokine network are thought to be important. But for human leptospirosis, data
      are limited. Because of the growing interest in this field, the impact of
      leptospirosis, and the availability of new therapeutic strategies, we reviewed
      the evidence regarding the role of coagulation in leptospirosis and provide
      suggestions for future research.

PMID- 17207156
TI  - Evaluation of the diethylcarbamazine patch to evaluate onchocerciasis endemicity
      in Central Africa.
AB  - OBJECTIVE: As part of a baseline data collection for assessing the impact of the
      African Programme for Onchocerciasis Control, to evaluate the diethylcarbamazine
      (DEC) patch test in determining the endemicity of onchocerciasis. METHOD: A total
      of 226 untreated children aged 3-5, living in four selected endemic foci, in
      Cameroon, Gabon and Central African Republic, were tested. Observed graded skin
      reactions to the patch were analysed and compared with the prevalence of
      onchocercal nodules and reactive skin disease in the corresponding community.
      RESULTS: The proportion of children who tested positive ranged from 25.0% to
      77.1%. The values were closely correlated with the prevalence of nodules, i.e.
      the level of endemicity for onchocerciasis. CONCLUSION: The DEC patch test, which
      has been so far used only in West African foci of onchocerciasis, can also
      constitute a valuable tool to evaluate the levels of endemicity of onchocerciasis
      in Central Africa, and to follow-up the intensity of transmission of Onchocerca
      volvulus.

PMID- 17207157
TI  - Prioritizing health problems in women in developing countries: comparing the
      financial burden of reproductive tract infections, anaemia and depressive
      disorders in a community survey in India.
AB  - OBJECTIVES: To compare the health care and opportunity costs of three common
      health problems [depressive disorders, reproductive tract infections (RTIs) and
      anaemia] affecting women and their associated risks of catastrophic health
      expenditure (defined a priori as out-of-pocket expenditure on health care
      exceeding 10% of the total monthly household income). METHODS: Cross-sectional
      survey of 2494 women who consented to participate, from a randomly selected
      sample of 3000 women aged 18-50, living in the catchment area of a primary health
      centre in Goa, India. Depressive disorders were diagnosed with the Revised
      Clinical Interview Schedule; anaemia on the basis of a fingerprick sample of
      blood using the Haemocue system; and RTI using PCR, culture and microscopy with
      vaginal or urine specimens. Economic consequences were measured using the Costs
      of Illness Schedule and the WHO Disability Assessment Schedule. Health provision
      costs were calculated using previously derived unit costs for services for the
      main types of health care provider. RESULTS: Catastrophic health expenditure,
      defined a priori as >10% of total household income spent out of pocket on health
      in the previous month, was reported by 138 women (5.5%; CI: 4.7-6.5%); they were
      more likely to report economic difficulties, such as having gone hungry in the
      past 3 months because of lack of money (OR 1.99, CI 1.1-3.6, P = 0.02). Only
      depressive disorder was associated with significantly higher health care costs,
      lost time costs and risk of catastrophic health expenditure (OR 2.66, CI 1.6-4.4,
      P < 0.001, after adjustment for possible sociodemographic confounders and other
      physical health problems). There was a linear association between the
      psychological morbidity score (arranged into quintile groups) and the risk of
      catastrophic health expenditure (adjusted). CONCLUSIONS: If economic arguments
      were considered a key driver for global health policy, then depressive disorder
      should be considered a major health priority for women in developing countries.

PMID- 17207158
TI  - Delivery of insecticide-treated net services through employer and community-based
      approaches in Kenya.
AB  - BACKGROUND AND OBJECTIVES: Many approaches have been used to deliver insecticide
      treated nets (ITNs) to African communities in different settings. Between 1992
      and 2002, the African Medical and Research Foundation (AMREF), Kenya, used two
      ITN delivery models: the employer-based approach and the community-based
      approach. These two approaches have never been compared in order to inform their
      potential for future ITN delivery. We aimed to (1) compare the extent of ITN
      ownership, use and retreatment coverage in different population groups in the
      employer and community-based models and (2) identify options for improving
      people's acceptance and use of treatment/retreatment services. METHODS:
      Qualitative and quantitative methods for data collection and analysis. A total of
      2095 household heads were interviewed in the quantitative study, while
      purposively selected groups and key informants participated in the qualitative
      study. RESULTS: Net coverage (both treated and untreated nets) and retreatment
      rates with insecticides were significantly higher at employer-based sites (54.3%)
      than at community-based sites (35.0%). Bed net ownership has increased
      significantly since the start of AMREF interventions in 1998 in employer-based
      sites (from 27% to 61.1%); in community-based sites, it has either decreased
      (urban area, from 29.0% to 16.5%) or increased (rural area, from 17.0% to 49.1%).
      Retreatment rates in all sites were negatively influenced by the lack of
      information, cash and availability of insecticides. Satisfaction with the form of
      payment and services delivered was higher in employer-based sites. This was
      attributed to employers providing credit for the purchase of nets and retreatment
      kits and the employers' medical teams giving information on malaria and making
      follow-up visits on workers who fell ill. CONCLUSIONS: Employer-based delivery of
      ITNs was more successful than community-based delivery in attaining both high
      coverage with ITNs and higher rates of net retreatment. Methods used for the
      retreatment of nets, forms of payment and communication strategies should be
      convenient to communities. Organized community groups may continue to play an
      important role in remote rural areas.

PMID- 17207159
TI  - Traditional practices and exposure to bodily fluids in Lusaka, Zambia.
AB  - OBJECTIVES: To ascertain if there are specific sociocultural and behavioural
      practices associated with the exposure to saliva, semen and vaginal fluids,
      particularly through child-rearing practices and the use of traditional medicine
      in Lusaka, Zambia. METHODS: We conducted 11 focus group discussions with men and
      women from diverse ethnic and socioeconomic backgrounds (n = 105) in Lusaka,
      Zambia in March 2004. We also conducted a brief sociodemographic survey of all
      focus group participants. RESULTS: Discussions indicated that saliva was used
      while engaging in home health care practices associated with childcare and the
      use of traditional medicine. Additionally, semen and vaginal fluids may be used
      in rituals associated with childcare and health care for children. Our survey
      indicated that the use of traditional medicine is associated with lower
      socioeconomic status. CONCLUSIONS: Population-based studies are needed to
      evaluate the relationship between traditional behavioural and sociocultural
      practices, which involve exchange of saliva and other bodily fluids and risk of
      infectious disease.

PMID- 17207160
TI  - An update on Behcet's disease.
AB  - Behcet's disease (Adamantiades-Behcet's disease, ABD) is a multisystemic
      inflammatory disease, the pathogenesis of which is still a mystery. Many
      questions are still to be answered and the available diverse data need to be
      brought together to be compared and analysed. There is at least consensus on the
      effect of possible, but currently unknown, environmental triggering factor(s)
      against a background of genetic susceptibility. The possible aetiological factors
      form a broad spectrum, with infectious agents being the most probable ones.
      Whatever the stimulus is, the target tissue seems to be the small blood vessels,
      with various consequences of either vasculitis and/or thrombosis in many organ
      systems. The endothelium seems to be the primary target in this disease; however,
      it may just be the subject of the bizarre behaviour of the immune system. The
      diverse existing data could be interpreted in favour of either explanation. A
      similar confusion exists about the thrombotic tendency in Adamantiades-Behcet's
      disease, in terms of whether a primary hypercoagulability is present or whether
      it is secondary to inflammation. Recent interesting immunological data promise a
      way out of the existing dilemma. These findings will be outlined within the
      context of possible hypotheses and attention will be paid to further
      investigations that are needed.

PMID- 17207161
TI  - Tunga penetrans: a stowaway from around the world.
AB  - Tungiasis is a cutaneous ectoparasitic infestation by the female sand flea Tunga
      penetrans. It is predominantly a health problem in sub-Saharan Africa, the
      Caribbean, Latin America and South America. However, increasing numbers of
      returning travellers, immigrants, and adopted children are also affected in non
      tropical countries. It is a cause of substantial morbidity, with prevalence rates
      as high as 76% in certain endemic areas. To date, the early extraction of the
      flea is still the first line therapy.

PMID- 17207162
TI  - Lupus erythematosus and other autoimmune diseases related to statin therapy: a
      systematic review.
AB  - BACKGROUND: Statins have been increasingly associated with drug-induced
      autoimmune reactions, including lupus erythematosus. OBJECTIVE: To identify and
      determine the clinical and biological characteristics of statin-induced
      autoimmune reactions. MATERIAL AND METHODS: The MEDLINE database (1966 to
      September 2005) was used to identify all reported cases of statin-induced
      autoimmune diseases. The keywords used were statins, 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitors, adverse effects, autoimmune disease, lupus
      erythematosus, dermatomyositis and polymyositis. RESULTS: Twenty-eight cases of
      statin-induced autoimmune diseases have been published so far. Systemic lupus
      erythematosus was reported in 10 cases, subacute cutaneous lupus erythematosus in
      three cases, dermatomyositis and polymyositis in 14 cases and lichen planus
      pemphigoides in one case. Autoimmune hepatitis was observed in two patients with
      systemic lupus erythematosus. The mean time of exposure before disease onset was
      12.8+/-18 months; range 1 month-6 years. Systemic immunosuppressive therapy was
      required in the majority of cases. In many patients, antinuclear antibodies were
      still positive many months after clinical recovery. A lethal outcome has been
      recorded in two patients despite aggressive immunosuppressive therapy.
      CONCLUSION: Long-term exposure to statins may be associated with drug-induced
      lupus erythematosus and other autoimmune disorders. Fatal cases have been
      reported despite early drug discontinuation and aggressive systemic
      immunosuppressive therapy.

PMID- 17207163
TI  - Bone mineral density and bone turnover markers of patients with Behcet's disease.
AB  - BACKGROUND: Behcet's disease (BD) is a systemic inflammatory disease of unknown
      aetiology. The pathogenesis of rheumatological findings and the status of bone
      metabolism in this disease are unknown. Inflammatory diseases may predispose to a
      decrease in bone mineral density (BMD) and there are many studies concerning
      osteoporosis in chronic inflammatory diseases. OBJECTIVE: The aim of this study
      was to investigate BMD and bone turnover markers in patients with BD. METHODS:
      Thirty BD patients (17 male and 13 female patients, mean age 36.9+/-12.6 years)
      and a total of 30 age- and sex-matched healthy controls (17 male and 13 female
      controls, mean age 34.9+/-8.95 years) recruited from the general population were
      enrolled in the study. Bone mineral density was measured at the lumbar spine (L1
      4) and the left hip (total hip) using dual energy X-ray absorptiometry. Serum
      samples were collected between 8 and 10 am after overnight fasting. Serum calcium
      (Ca), phosphate (P), parathormone (PTH), total alkaline phosphatase (ALP),
      osteocalcin (OC), erythrocyte sedimentation rate (ESR), and C-reactive protein
      (CRP) were measured. Free deoxypyridinoline cross-links (DPD) in second-void
      urine and total daily urinary calcium excretion were analysed. RESULTS: No
      statistically significant difference in lumbar spine or femoral BMD and bone
      turnover markers were found between BD patients and control groups (P>0.05).
      CONCLUSION: Although it is difficult to draw definite conclusions because of the
      limited number of patients involved, our study indicates that bone mineral
      density and bone turnover markers in Behcet's disease were no different than in
      healthy subjects.

PMID- 17207164
TI  - The additive value of second opinion teleconsulting in the management of patients
      with challenging inflammatory, neoplastic skin diseases: a best practice model in
      dermatology?
AB  - BACKGROUND: Telemedicine is the practice of healthcare using interactive
      processes of communication to facilitate healthcare delivery, including
      diagnosis, consultation and treatment, as well as education and transfer of
      medical data. The aim of teledermatology, just as telemedicine, is to promote
      best practice procedures and to improve the consistency and competence of health
      care. AIM: To investigate the diagnostic additive value of second opinion
      teleconsulting in patients with challenging dermatoses, among dermatologists
      working in two different dermatology departments. SETTING: Thirty-three cases of
      patients with challenging inflammatory and neoplastic skin diseases at the
      University of L'Aquila Department of Dermatology were sent for teleconsultation
      to the Department of Dermatology, Medical University of Graz, Austria. METHODS:
      All cases were selected in the outpatient service in L'Aquila. After face-to-face
      consultation with a local colleague had been completed, images were sent using a
      store-and-forward (SAF)-based system (http://www.telederm.org) to Graz.
      Histopathological examination together with follow-up of the patient represents
      the diagnostic gold standard for this study. RESULTS: Telediagnosis was correct
      in 26 of 33 (78.8%) cases. Sixteen of 33 cases (48.5%) had already been diagnosed
      face-to-face by at least one of the two dermatologists in L'Aquila. In 10 of 33
      cases (30.3%), the correct diagnosis was made in teleconsultation only.
      CONCLUSIONS: Second opinion teleconsulting may represent an additive value in the
      diagnosis of numerous challenging inflammatory and neoplastic skin diseases. It
      may be particularly useful as a best practice model for smaller departments in
      order to discuss and/or to confirm diagnoses and also for the management of
      patients with unusual difficult dermatoses.

PMID- 17207165
TI  - The autologous serum skin test in a cohort of chronic idiopathic urticaria
      patients compared to respiratory allergy patients and healthy individuals.
AB  - BACKGROUND: A positive autologous serum skin test (ASST) is considered to reflect
      the presence of anti-FceRI and/or anti-IgE autoantibodies that are capable of
      activating mast and basophil cell degranulation. The ASST is regarded as a
      reliable in vivo test in chronic idiopathic urticaria (CIU) patients, with
      diagnostic, therapeutic and prognostic implications. However, positive ASST
      results have also occasionally been demonstrated in patients with other diseases
      and in healthy subjects. OBJECTIVE: To evaluate the specificity and sensitivity
      of the ASST in a cohort of CIU patients compared to a cohort of respiratory
      allergic patients and a group of normal individuals. METHODS: ASST was performed
      in a cohort of 116 subjects, 47 subjects with seasonal allergic rhinitis, 32
      respiratory-symptom-free CIU patients, and 37 healthy individuals. RESULTS: The
      results were compared statistically to those of the CIU patients. The intradermal
      injection of autologous serum induced a weal and flare reaction in 17/32 (53.1%)
      CIU patients; 14/47 (29.8%) patients with seasonal allergic rhinitis (P=0.06) and
      in 15/37 (40.5%) of the healthy controls (P=0.34). The sensitivity and
      specificity of the ASST in the CIU patients and the seasonal allergic rhinitis
      patients was 53 and 28%, respectively. When comparing the CIU patients with the
      healthy controls the sensitivity and specificity was 55 and 31%, respectively.
      The positive and negative predictive values of the ASST when comparing CIU
      patients with healthy controls were 53 and 59.5%, respectively. The positive and
      negative predictive values of the ASST in the CIU patients compared to seasonal
      allergic rhinitis patients were 53 and 70%, respectively. CONCLUSION: The
      relatively low sensitivity and specificity of the ASST in the CIU patients
      compared to the seasonal allergic rhinitis patients and healthy controls warrants
      a more critical interpretation of the ASST in chronic idiopathic urticaria.

PMID- 17207166
TI  - Cutaneous tuberculosis in children and adolescents: a clinicohistological study.
AB  - BACKGROUND AND OBJECTIVES: Resurgence of tuberculosis (TB) in the era of human
      immunodeficiency virus (HIV) has rejuvenated the interest in this global health
      problem. Cutaneous TB, an important extra-pulmonary form in children, is commonly
      seen in our dermatological practice. As detection of acid-fast bacillus (AFB) on
      smear or culture is not always positive, histopathology is necessary to help in
      diagnosing and classifying the variants of skin TB. The current study was
      conducted to analyse the clinicopathological characteristics of cutaneous TB in
      children and adolescents. MATERIALS AND METHODS: This prospective study included
      103 patients (age<19 years). A detailed history and clinical examination was
      followed by complete investigative work up including fine needle aspiration
      cytology and culture. Histopathological evaluation was performed specifically
      noting the epidermal and dermal features. The patients were followed up regularly
      for one year after the start of treatment. RESULTS: The different patterns of
      cutaneous TB seen were, scrofuloderma 38 (36.9%), lichen scrofulosorum 34 (33%),
      lupus vulgaris 22 (21.3%), TB verrucosa cutis 4 (3.9%), papulonecrotic tuberculid
      4 (3.9%) and erythema nodosum 3 (2.9%). Systemic associations were seen in 55
      (53.4%) patients, namely TB lymphadenitis in 30 (29.2%), pulmonary TB in 13
      (12.6%), abdominal TB in 6 (5.8%) and TB arthritis in 6 (5.8%). The
      histopathological corroboration of clinical diagnosis was seen in 65.7% of cases
      of scrofulodermas, 72.7% of cases of lupus vulgaris and 67.6% of cases of lichen
      scrofulosorum. CONCLUSIONS: A large spectrum of clinical patterns and
      histological characteristics of cutaneous TB exists in children. Lichen
      scrofulosorum is more commonly seen in comparison to adults. Systemic involvement
      was a feature in a major proportion of our patients.

PMID- 17207167
TI  - Digital computer analysis of dermatoscopical images of 260 melanocytic skin
      lesions; perimeter/area ratio for the differentiation between malignant melanomas
      and melanocytic nevi.
AB  - BACKGROUND: Digital computer analysis of dermatoscopical images has been reported
      to facilitate the differential diagnosis of pigmented skin lesions in recent
      years. OBJECTIVE: The aim of our study was to perform digital computer analysis
      of a set of different melanocytic lesions and compare the objective results.
      METHODS: The set of 260 melanocytic lesions (150 excised difficult cases (46
      melanomas, 47 atypical nevi, 57 common nevi and 110 unexcised common nevi) was
      automatically analysed by the digital dermatoscopical system microDERM. We
      searched for differences in asymmetry, size, compactness and colour distribution.
      Perimeter/area ratio was calculated. RESULTS: The perimeter/area ratio was
      detected as the most important criterion for differentiation between malignant
      and benign melanocytic lesions (sensitivity 91.3% and specificity 90.7% for
      malignant melanomas vs. all benign nevi; sensitivity 91.3% and specificity 80.8%
      for melanomas vs. clinically atypical nevi). Differences in size of the lesion,
      shape and asymmetry of colour were found and statistically verified. Using step
      wise logistic regression the formula for calculation of probability of malignant
      nature of every analysed lesion was constructed. CONCLUSION: The perimeter/area
      ratio is a simple parameter for the differential diagnosis of melanocytic skin
      lesions.

PMID- 17207168
TI  - Melanoma/skin cancer screening in a Mediterranean country: results of the
      Euromelanoma Screening Day Campaign in Greece.
AB  - BACKGROUND: Since the year 2000 a melanoma/skin cancer screening campaign has
      been organized annually in Greece in the context of the Euromelanoma Screening
      Day Campaign. OBJECTIVES: We aimed to analyse the characteristics of the screened
      population, to recognize relevant risk factors and to identify the cases of
      histologically confirmed malignant melanoma (MM) in individuals with suspicious
      skin lesions. METHODS: An analysis of the completed screening forms from the
      years 2000-2004 was performed with respect to relevant demographic,
      epidemiological and clinical data. RESULTS: A total of 9723 individuals were
      screened, most of whom where below the age of 50 years (71%), female (59%), and
      of skin phototype II and III (76%). Sunburn during childhood was reported in 47%
      of participants, while 5% of the screened population had a personal or family
      history of melanoma. On clinical examination, 14.4% had actinic keratoses, 31.2%
      had dysplastic nevi, while 6.4% carried a presumptive diagnosis of non-melanoma
      skin cancer. In the 2003-2004 screening campaign, 19 out of the 171 clinically
      suspicious lesions were histologically proven to be MM, the majority of which
      (58%) were 'thin' melanomas (Breslow's thickness of<or=1 mm) of the superficial
      spreading type. CONCLUSIONS: Our study suggested that, a melanoma/skin cancer
      screening programme in a Mediterranean country, supported by an intense publicity
      campaign, attracted many individuals at risk for skin cancer and detected mostly
      thin melanomas of the superficial spreading type.

PMID- 17207169
TI  - Paediatric eczema and psychosocial morbidity: how does eczema interact with
      parents' illness beliefs?
AB  - BACKGROUND: Thus far there has been relatively little work on children's illness
      representations regarding eczema and how these relate to parental
      conceptualizations of their child's psychosocial health. This is important
      because the challenge of raising a child with a serious illness can affect many
      facets of a parent's everyday life and the behaviour of parents can be closely
      related to the health of the child. METHODS: Two hundred and thirty-two children
      with eczema, asthma, eczema and asthma, and healthy controls between 7 and 12
      years of age and their parents were recruited. Children were administered the
      Children's Illness Perception Questionnaire. Questionnaires completed by the
      parents were The Personality Inventory for Children and The Parental Stress
      Inventory. RESULTS: Parents of children with eczema did not judge their children
      to have poorer psychosocial health than controls, but parents of children with
      eczema could not be distinguished between in terms of whether their child was
      significantly affected by their eczema or not. CONCLUSIONS: This work could have
      important implications for the quality of life of the child and for the parent
      child relationship and these implications are considered.

PMID- 17207170
TI  - Lack of association between leptin G2548A gene polymorphism and Behcet's disease.
AB  - BACKGROUND: Behcet's disease is a chronic, multisystem, inflammatory disease
      characterized by the predominance of T-helper 1 cytokines. The disease is also
      characterized by infiltration of lymphocytes and neutrophils into the affected
      tissues. Because cytokines are involved in the regulation of lymphocyte and
      phagocyte functions, they may play an important role in the pathogenesis of
      Behcet's disease. Leptin, a member of the gp 130 family of cytokines, induces a
      strong T-helper 1 response and is regarded as a proinflammatory inducer. Recent
      studies have shown that serum leptin concentration was increased in patients with
      Behcet's disease and correlated with disease activity. OBJECTIVES: We aimed to
      investigate the role of G2548A polymorphism of leptin gene in patients with
      Behcet's disease and compare the results with healthy controls. PATIENTS AND
      METHODS: A total of 93 subjects with Behcet's disease and 125 healthy controls
      were included in this study. Analyses of G-2548A polymorphism of the LEP gene
      were performed using the PCR-restriction fragment length polymorphism technique.
      The genotypes (GG, GA, and AA of leptin G2548A) and alleles (G and A of leptin
      2548) were scored and the frequency was estimated. The frequencies of the alleles
      and genotypes in patients and controls were compared. We analysed the correlation
      between leptin gene polymorphism and the clinical features of BD. RESULTS: Both
      genotype and allele frequencies were not significantly different between controls
      and Behcet's disease patients [OR=0.67, 95% CI (0.35-1.29), P=0.197 and OR=0.77,
      95% CI (0.52-1.15), P=0.184]. We did not find any significant relationship
      between leptin gene polymorphism and the clinical features of BD (P>0.05).
      CONCLUSION: In the present case-control study, we found no evidence of an
      association between the G-2548A variant of the leptin gene and BD among Turks.
      Further studies are needed to investigate serum leptin level to explain the
      mechanisms behind the lack of association between leptin G2548A gene polymorphism
      and BD.

PMID- 17207171
TI  - Vascular adhesion protein-1 (VAP-1) is overexpressed in psoriatic patients.
AB  - BACKGROUND: Vascular adhesion protein (VAP)-1 is an adhesion molecule with an
      enzymatic activity that partakes in the migration process of lymphocytes.
      OBJECTIVES: The aim of this study was to investigate the expression of VAP-1 in
      the skin and serum of psoriatic patients. MATERIAL AND METHODS: Seventy-one
      patients suffering from psoriasis aged between 23 and 89 years were included in
      the study. The mean psoriasis severity assessed according to the psoriasis area
      and severity index was 14.2+/-9.6 points. The soluble VAP-1 serum concentration
      was evaluated by ELISA and VAP-1 expression in the skin (nine patients)
      immunohistochemically. RESULTS: The serum concentration of soluble VAP-1 was
      significantly higher in psoriatic patients than in healthy controls (403.4+/
      130.8 ng/mL vs. 246.4+/-68.0 ng/mL; P<0.0001). No significant relationships were
      found between sVAP-1 concentration and studied clinical parameters, except the
      presence of pruritus. Mean number of VAP-1 positive vessels in psoriatic skin,
      both lesional (19.8+/-1.4) and non-lesional (9.4+/-1.4), was significantly higher
      than in healthy skin (5.4+/-1.5; P<0.005). Lesional psoriatic skin demonstrated
      significantly more VAP-1 positive vessels than non-lesional skin (P<0.01).
      CONCLUSIONS: Significant overexpression of VAP-1 in both lesional and non
      lesional psoriatic skin and higher serum level of soluble VAP-1 in psoriatic
      patients may indicate the role of VAP-1 in chronic inflammation occurring in
      psoriasis. However, because of lack of correlation between soluble VAP-1 serum
      levels and psoriasis severity this hypothesis needs further investigation.

PMID- 17207172
TI  - Accelerating effects of epidermal growth factor on skin lesions of pemphigus
      vulgaris: a double-blind, randomized, controlled trial.
AB  - BACKGROUND: Pemphigus vulgaris (PV) is a severe blistering disease involving the
      skin and mucous membranes. The most common causes of death in these patients are
      adverse effects of drugs, and infection. Skin lesions are one of the important
      sources of infection. Thus, any local treatment that could reduce healing time of
      lesions and consequently reduce the total dosage of drugs needed to treat is
      favourable. OBJECTIVE: To evaluate the efficacy of epidermal growth factor (EGF)
      in reducing healing time of lesions in patients with pemphigus vulgaris. METHODS:
      In this randomized, double-blind, within-patient, left/right, controlled trial,
      20 hospitalized patients with pathologial and immunohistologial (direct and
      indirect immunoflourecence) proven pemphigus vulgaris (PV) were chosen. In
      addition, all patients had at least one appropriate pemphigus lesion on each side
      of the body that had not healed after 2-week systemic therapy and sterile saline
      washing. EGF (10 microg/g) in 0.1% silver sulfadiazine cream vs. 0.1% silver
      sulfadiazine cream alone was applied randomly on one side of the body. RESULTS:
      Kaplan-Meier survival analysis suggested that median time to heal with
      application of EGF plus silver sulfadiazine cream was 9 days, in comparison with
      15 days for silver sulfadiazine cream alone (log-rank test, P=0.0003). No
      intervention-related adverse effect was observed during the study. CONCLUSIONS:
      EGF can significantly reduce healing time of skin lesions in patients with
      pemphigus vulgaris, at least when this cream base is applied (Cochrane skin group
      identifier: CSG20).

PMID- 17207173
TI  - Efficacy and safety of long-term treatment with cyclosporin A for atopic
      dermatitis.
AB  - BACKGROUND: Cyclosporin A (CsA) is being increasingly used in the treatment of
      severe refractory atopic dermatitis. Clinical efficacy and safety of short-term
      cyclosporin A treatment in atopic dermatitis patients has been proven, however,
      data on long-term treatment are limited. OBJECTIVE: The aim of this study was to
      investigate the efficacy, safety and the effect of discontinuation of cyclosporin
      A treatment in atopic dermatitis patients, with a particular focus on patients
      treated with cyclosporin A for more than 6 months. METHODS: We performed a
      retrospective study of clinical and adverse effects of cyclosporin A treatment in
      73 atopic dermatitis patients, with an average duration of cyclosporin A
      treatment of 1.3 years. RESULTS: We included 73 patients (31 women and 42 men,
      with a mean age of 33.8 years) with severe atopic dermatitis refractory to
      conventional therapy that was treated with cyclosporin A. Treatment was
      successful in 56/73 patients. Increases in serum creatinine levels > 30% compared
      to baseline were reported in 7/73 patients. Arterial hypertension appeared in
      11/73 patients during treatment. After discontinuation of treatment, 40/73
      patients experienced a relapse and 33/73 patients experienced clinical remission
      for at least 3 months. No correlation between treatment duration and
      nephrotoxicity or hypertension was found. Strikingly, 6/73 patients experienced a
      rebound phenomenon. CONCLUSIONS: We conclude that CsA is an effective and safe
      treatment for patients with severe AD refractory to conventional treatment,
      provided that the recommended guidelines for its administration are strictly
      observed. However, in contrast to previous reports, we found that 8% (6/73) of
      patients experienced a rebound phenomenon after discontinuation of treatment.

PMID- 17207174
TI  - Pimecrolimus cream 1% is effective in asteatotic eczema: results of a randomized,
      double-blind, vehicle-controlled study in 40 patients.
AB  - BACKGROUND AND OBJECTIVE: Pimecrolimus cream 1% is an effective treatment for
      atopic eczema. The aim was to investigate its efficacy in asteatotic eczema, a
      skin disease similar to atopic eczema and its associated dry skin and itching.
      METHODS: Single-centre, randomized, double-blind, vehicle controlled study in 40
      patients with asteatotic eczema. Efficacy was assessed by eczema area and
      severity index (EASI), investigators global assessment (IGA), patient's self
      assessment, and pruritus severity. RESULTS: After 4 weeks of treatment, EASI, the
      primary efficacy variable, was reduced by 62+/-7% from baseline in patients on
      pimecrolimus, compared to 21+/-14% in patients on vehicle (P=0.013). With
      pimecrolimus there was also a better control of pruritus (P=0.042) at week 4
      whereas a better control of disease according to self-assessment could only be
      observed at weeks 2 (P=0.01) and week 3 (P=0.08). CONCLUSION: Pimecrolimus cream
      1% is effective in patients with asteatotic eczema.

PMID- 17207175
TI  - Predictors of skin self-examination in subjects attending a pigmented lesion
      clinic in Italy.
AB  - BACKGROUND: Skin self-examination (SSE) is associated with thinner melanomas in
      both North American and Italian patients. The knowledge of conditions associated
      with SSE may help in refining educational strategies for the prevention of
      melanoma. OBJECTIVE: The aim of the study was to investigate the frequency of SSE
      and the factors associated with SSE in subjects followed at a specialized
      pigmented lesion clinic (PLC) in Italy. PATIENTS/METHODS: A series of 299
      consecutive subjects who visited the Florence PLC was investigated by means of a
      self-administered questionnaire regarding SSE habits. The statistical association
      between SSE and selected variables was examined by univariate and multivariate
      analyses. RESULTS: In the univariate analysis, variables significantly associated
      with SSE were: green/blue eyes, phototype I/II, the presence of large numbers of
      common acquired and atypical melanocytic naevi, sunscreen use, having had a
      previous PLC examination, and having received a leaflet explaining SSE. SSE was
      less frequent in women using sunbeds and more frequent in those performing breast
      self-examination. Using the multivariate model, which included all the variables
      associated with SSE in the previous analysis, we found that, among males, the
      only variable significantly associated with SSE was the report of having received
      a leaflet explaining SSE [odds ratio (OR) 3.02, 95% confidence interval (CI) 1.24
      7.38]. Among females, having had a previous consultation at a PLC was
      significantly associated with SSE (OR 4.84, 95%CI 1.57-14.93); this might be
      because of the explanation and advice about skin cancer prevention customarily
      provided as a part of the PLC consultation at our department. CONCLUSION:
      Educational tools, including a leaflet explaining SSE and counselling given
      within previous PLC visits, seem to play a crucial role in promoting SSE habits
      in subjects followed at a specialized PLC consultation.

PMID- 17207176
TI  - Sitosterol xanthomatosis.
AB  - BACKGROUND: Sitosterolaemia is a lipid disorder in which plasma plant sterol
      levels are extremely elevated. Sitosterolaemia is clinically characterized by
      tuberous and tendon xanthomas, premature vascular disease and arthritis.
      OBJECTIVE: To report a case of sitosterolaemia diagnosed by cutaneous
      manifestations and to review this rare disease. METHODS: We report the case of a
      60-year-old woman who presented with cutaneous xanthomas, arterial hypertension
      and polyarthralgias. The patient had had hypercholesterolaemia for many years
      without reduction of serum cholesterol, despite treatment with fenofibrate.
      RESULTS: Ezetimibe therapy was started, decreasing sitosterol plasmatic levels
      and tuberous xanthomas after 3 months of treatment. CONCLUSION: It is important
      to detect levels of sitosterol in plasma in patients with premature vascular
      disease, presence of xanthomas, and uncontrolled hypercholesterolaemia. Ezetimibe
      therapy is effective.

PMID- 17207177
TI  - Erythema elevatum diutinum in the spectrum of palisaded neutrophilic
      granulomatous dermatitis: description of a case with rheumatoid arthritis.

PMID- 17207178
TI  - Unilateral xanthelasma sparing a paralysed eyelid.

PMID- 17207179
TI  - Cutaneous malignant fibrous histiocytoma in an HIV-positive patient.

PMID- 17207180
TI  - Delayed foreign body granuloma secondary to an abandoned cardiac pacemaker wire.

PMID- 17207181
TI  - Follicular involvement in porokeratosis.

PMID- 17207182
TI  - Extensive keloids following cyclosporin therapy in a pemphigus vulgaris patient.

PMID- 17207183
TI  - Recurrent classic Kaposi's sarcoma in a Japanese man: detection of human
      herpesvirus 8 infection by PCR and immunostaining.

PMID- 17207184
TI  - Extensive genital bowenoid papulosis responding to imiquimod.

PMID- 17207185
TI  - Dermatophyte onychomycosis in children under 2 years of age: experience of 16
      cases.

PMID- 17207186
TI  - Rhinofacial zygomycosis successfully treated with oral saturated solution of
      potassium iodide: a case report.

PMID- 17207187
TI  - Acantholytic acanthoma clinically resembling a molluscum contagiosum.

PMID- 17207188
TI  - Unilateral areolar sebaceous hyperplasia in a male.

PMID- 17207189
TI  - Eccrine spiradenoma: co-expression of cytokeratin and smooth muscle actin
      suggesting differentiation toward myoepithelial cells.

PMID- 17207190
TI  - Cutaneous metastasis of gastric signet ring cell carcinoma masquerading as
      allergic contact dermatitis.

PMID- 17207191
TI  - Reduced growth of beard as the only diagnostic sign in a patient with
      macroprolactinoma.

PMID- 17207192
TI  - Major oral aphtous ulceration in HIV-1 infection: successful response after
      highly active antiretroviral therapy.

PMID- 17207193
TI  - A case of chromonychia with hyperbilirubinemia.

PMID- 17207194
TI  - Scleromyxoedema treated with autologous stem cell transplantation.

PMID- 17207195
TI  - Becker naevus associated with basal cell carcinoma, melanocytic naevus and smooth
      muscle hamartoma.

PMID- 17207196
TI  - Lupus erythematosus profundus in an 8-year-old child.

PMID- 17207197
TI  - Rippled-pattern sebaceoma with an immunohistochemical study of cytokeratins.

PMID- 17207198
TI  - Annular leukocytoclastic vasculitis in association with chronic hepatitis B.

PMID- 17207199
TI  - Acute myocardial infarction in a patient with cutaneous lupus erythematosus
      treated with thalidomide.

PMID- 17207200
TI  - Granulomatous periorificial dermatitis in an 11-year-old boy: dramatic response
      to tacrolimus.

PMID- 17207201
TI  - Microscopic aspects of pili canaliculi.

PMID- 17207202
TI  - Is there any relation between vitiligo and cytomegalovirus?

PMID- 17207203
TI  - Psoriasis of the lips: a rare entity.

PMID- 17207206
TI  - Professional sadness: when patient care clashes with the bottom line.

PMID- 17207207
TI  - Routine HIV screening recommended.

PMID- 17207208
TI  - Getting involved in research: lessons learned from a novice researcher.

PMID- 17207209
TI  - Spirituality and high-risk pregnancy: another aspect of patient care.
AB  - A high-risk pregnancy can be a stressful situation for a woman, her partner and
      her family. Many women utilize their spiritual beliefs as a way to make sense of
      their situation. Health care professionals, including nurses, midwives and
      physicians, can provide effective spiritual care and support consistent with
      their professional scopes of practice. Spiritually focused interventions can help
      to reduce stress and anxiety and create a more open and confident approach to the
      management of pregnancy complications.

PMID- 17207210
TI  - The business of nursing: experts discuss budgets, staffing, safety and more.

PMID- 17207211
TI  - Eating disorders: identification and treatment in obstetrical patients.
AB  - Eating disorders are well defined in females ages 14 to 24, and consist primarily
      of anorexia nervosa (AN) and bulimia nervosa (BN). Collectively, these two eating
      disorders are characterized by severe disturbances in eating behaviors and acute
      distress over body shape and weight. In AN, fear of weight gain coupled with a
      distorted body image leads to refusal to maintain a minimally accepted body
      weight (American Psychiatric Association [APA], 1994). Although women with BN
      also overvalue body size and shape, this disorder is characterized by episodes of
      binge eating followed by efforts to undo the binge episode (oral purging is the
      most widely known effort) (APA, 1994). Developmental, psychological,
      socioenvironmental and behavioral factors contribute to the complex development
      and persistence of AN and BN (Rosen & Neumark-Sztainer, 1998).

PMID- 17207212
TI  - Challenges of breastfeeding preterm infants: a case study.
AB  - Promoting breastfeeding of preterm infants offers clinical challenges for
      maternal-child nurses, and requires understanding the experience of the mother.
      Maternal-child nurses, in collaboration with hospital- and community-based
      lactation specialists, can meet the unique needs of preterm infants and their
      mothers. There are several opportunities for nurses to educate other health care
      professionals in the care of preterm infants and their mothers. The case study in
      this article presents one mother's experience of delivering a preterm infant and
      the many obstacles to breastfeeding that she encountered, and it also offers
      suggestions for what nurses and other health care professionals can do to make
      sure other mothers have a more positive experience.

PMID- 17207213
TI  - Listeriosis: how nurses can prevent the preventable.

PMID- 17207214
TI  - Primary care safety: improving outcomes in the ambulatory setting.

PMID- 17207215
TI  - Great leaders are made, not born: conclusion of a four-part series.

PMID- 17207219
TI  - The honor of your presence.

PMID- 17207221
TI  - Clinical research design and reporting: always room for improvement!

PMID- 17207222
TI  - Making a stealth organ by RNA inhibition: will it fly?

PMID- 17207223
TI  - Identifying babies with neonatal alloimmune thrombocytopenia and the responsible
      antigens.

PMID- 17207224
TI  - How we manage requests for recombinant factor VIIa (NovoSeven).

PMID- 17207225
TI  - The research question.

PMID- 17207226
TI  - Regulating MHC expression for cellular therapeutics.
AB  - BACKGROUND: In the past decade, regenerative medicine and cell-based therapies
      have emerged as new science and technology, with the main goal of repairing,
      replacing, or regenerating new tissues. A critical issue in this field is the
      high polymorphism of HLA, which compromises immune acceptance. The lentivirus
      mediated delivery of short-hairpin RNAs (shRNAs) has proved to be an efficient
      method to inhibit the translation of a specific gene. STUDY DESIGN AND METHODS: A
      lentiviral-based vector system was used for drug-inducible expression of shRNA
      sequences that target either beta2-microglobulin (beta2m) or HLA heavy-chain
      transcripts. RESULTS: The transduction of inducible RNA interference cassettes
      containing the sequences for shRNAs targeting beta2m or HLA heavy chain
      suppressed HLA class I expression by up to 90 percent in HeLa and B-lymphocyte
      cell lines as well as in peripheral blood monocytes. The expression of HLA class
      I antigens was fully restored in these cells after the drug had been
      discontinued. It was demonstrated that HLA class I knockdown was effective in
      preventing antibody-mediated cell lysis and CD8+ T-cell response. The residual
      HLA expression in HLA-silenced cells may provide sufficient protection against
      natural killer cell-mediated lysis. CONCLUSIONS: These data demonstrate the
      feasibility of controlling HLA expression by genetically modifying cell-based
      therapeutics to overcome the limitations of immune rejection, bringing cellular
      therapies closer to reality.

PMID- 17207227
TI  - Duffy and Kidd blood group antigens: minor histocompatibility antigens involved
      in renal allograft rejection?
AB  - BACKGROUND: Minor histocompatibility antigens have been poorly defined. Whether
      Duffy (FY) and Kidd (JK), polymorphic and immunogenic blood group antigens,
      widely distributed in human organs, expressed and functional in the kidney, could
      function as minor histocompatibility antigens and be implicated in renal
      allograft rejection was questioned. STUDY DESIGN AND METHODS: A retrospective,
      homogeneous, single-center cohort of 370 renal transplants was analyzed. In all
      donor/recipient pairs, FY and JK polymorphisms were identified by real-time
      polymerase chain reaction. In all donor/recipient pairs the matching (m) or
      mismatching (mm) status was defined for both systems. All biopsies were reviewed,
      and historical screening results for FY and JK alloantibodies and graft survival
      were retrospectively analyzed. RESULTS: Although graft survival was not different
      between the groups, it was observed that FY mm grafts had significantly more
      chronic lesions compared to FY m grafts. HLA-DR11 was more frequent in both
      recipients (p = 0.0081) and donors (p = 0.0104) of FY mm couples without chronic
      allograft nephropathy, suggesting a protective effect for this molecule. JK mm
      grafts had more interstitial inflammation than JK m grafts (p = 0.0369).
      CONCLUSION: This renal model unmasks for the first time the role of FY and-to a
      lesser extent-JK antigens as minor histocompatibility antigens and suggests their
      potential role for other clinical transplant settings.

PMID- 17207228
TI  - Thrombocytopenia in association with splenomegaly during granulocyte-colony
      stimulating factor treatment in mice is not caused by hypersplenism and is
      resolved spontaneously.
AB  - BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) is used for
      hematopoietic progenitor cell (HPC) mobilization. Platelet (PLT) counts decrease
      during G-CSF administration. The mechanisms have not been determined, however.
      Because splenic pooling of PLTs caused thrombocytopenia in patients with
      splenomegaly and splenic enlargement was observed in G-CSF-treated donors, it was
      hypothesized that hypersplenism might cause G-CSF-induced thrombocytopenia. STUDY
      DESIGN AND METHODS: Mice were treated with several concentrations of G-CSF, and
      PLT count was measured. Because transfused PLTs should be cleared rapidly from
      the blood stream under hypersplenic state, PLT life span was studied. To
      determine direct role of spleen on thrombocytopenia, G-CSF was given to
      splenectomized mice. Because PLT count did not decrease in G-CSF-expressing
      transgenic mice, G-CSF was given to mice for a longer period of time and PLT
      count was investigated. RESULTS: PLT counts decreased while spleen weight
      increased in a dose-dependent manner by G-CSF treatment. No significant
      difference in PLT life span was found between G-CSF-treated and control mice.
      Histologic analysis showed no significant increase in PLT numbers trapped in
      either spleen or other tissue after PLT transfusion in G-CSF-treated mice. In
      splenectomized mice as well as in normal mice, G-CSF caused thrombocytopenia.
      When G-CSF was given to mice for a longer period of time, PLT counts decreased
      during the first 7 days and thereafter began to increase followed by returning to
      baseline on Day 15. CONCLUSION: Thrombocytopenia coincided with splenomegaly
      during G-CSF treatment, but hypersplenism was not responsible for
      thrombocytopenia. G-CSF-induced thrombocytopenia was a transient event and
      improved spontaneously despite continual G-CSF treatment.

PMID- 17207229
TI  - Autoimmune hemolytic anemia in childhood: serologic features in 100 cases.
AB  - BACKGROUND: Red blood cell (RBC) autoimmunization is a relatively uncommon cause
      of anemia in children and presents some differences from those of adults. Due to
      its frequency, autoimmune hemolytic anemia (AIHA) in childhood has prompted very
      few studies, and the literature consists mostly of sporadic case histories. The
      objective of this study was to stress the importance of an appropriate serologic
      diagnosis in suspected cases. STUDY DESIGN AND METHODS: This report describes the
      immunohematologic features of 100 patients with AIHA studied in the
      Immunohaematologic Unit of Blood Bank, "La Sapienza" University of Rome. The
      patients were diagnosed in the same department from 1983 to 2003. RESULTS: The
      peak incidence of AIHA was in the first 4 years of life. No sex predominance was
      noted. Warm AIHA was the most common type of acquired immune hemolytic anemia; it
      comprised 64 of the 100 patients, whereas 26 patients showed a cold AIHA.
      Associated AIHA showed a slightly more frequent incidence (54/100) compared to
      idiopathic forms of AIHA (46/100). CONCLUSIONS: In this study serologic records
      of 100 children with confirmed AIHA are reported. This series, much larger than
      any previously reported, is critically reviewed and analyzed to delineate the
      immunologic features of the disease in childhood.

PMID- 17207230
TI  - Maternal human platelet antigen-1a antibody level correlates with the platelet
      count in the newborns: a retrospective study.
AB  - BACKGROUND: Maternal plasma and/or serum levels of anti-HPA-1a at delivery were
      compared to neonatal platelet (PLT) counts. STUDY DESIGN AND METHODS: Samples
      from HPA-1bb women who gave birth to children with thrombocytopenia or had
      anamnestic information about a previous child with neonatal alloimmune
      thrombocytopenia (NAIT) were collected at delivery. A modified monoclonal
      antibody immobilization of PLT antigen method was used for quantification of anti
      HPA-1a. RESULTS: The anti-HPA-1a level in women with severely thrombocytopenic
      children was higher than the corresponding level in mothers of children born with
      moderate thrombocytopenia or normal PLT counts. CONCLUSION: Our data show a
      significant correlation between maternal anti-HPA-1a level and the neonatal PLT
      count and indicate strongly that this may be a reliable predictive measure for
      NAIT. Suitable test systems for quantitative measurements of anti-HPA-1a must be
      developed and evaluated for this particular purpose.

PMID- 17207231
TI  - A prospective study on the prevalence and risk factors for neonatal
      thrombocytopenia and platelet alloimmunization among 9332 unselected Brazilian
      newborns.
AB  - BACKGROUND: Neonatal thrombocytopenia (NT) occurs in 0.5 to 0.9% of unselected
      Caucasian newborns. However, the prevalence of this complication in other
      populations is unknown. In this study the prevalence/causes of NT was determined
      in Brazilian newborns, a population characterized by admixture among Indigenous,
      Africans, and Caucasians. STUDY DESIGN: A prospective study was carried out in a
      3-year period, to determine the prevalence and causes of thrombocytopenia in cord
      blood samples. Genotyping for HPA 1-5 systems was performed in pairs of
      mother/neonates with and without thrombocytopenia. All mothers with genotypic
      mismatches from each group were tested for HPA-specific antibody using the MAIPA
      technique to identify alloimmunization. RESULTS: Platelet counts <100 x 10(9)/L
      were detected in 1.5% of 9,332 unselected newborns. In 0.15%, platelet count was
      <50 x 10(9)/L. Clinically significant bleeding was rare. Underlying diseases were
      present in 48% of the thrombocytopenic cases. HPA 1-5 system genotype mismatches
      occurred in 50% of gestations, but did not predict the risk for thrombocytopenia.
      Notably, mismatched genotypes for HPA-5 were slightly increased in the
      thrombocytopenic group. The presence of anti-HPA-5b antibodies was observed in
      0.05% of unselected pregnancies, but increased to 12% among mothers of neonates
      with thrombocytopenia and mismatched genotype (N = 51). CONCLUSIONS: Neonatal
      thrombocytopenia is common among Brazilian newborns at rates comparable with
      those described among Caucasians. These data suggest that screening for genotypic
      HPA mismatch, followed by an HPA-specific immunoassay system, particularly for
      the HPA-5 system, among mothers of newborns with thrombocytopenia in our
      population would allow the identification of pregnancies at risk of alloimmune
      thrombocytopenia.

PMID- 17207232
TI  - Platelet function in whole-blood donors is impaired: the effects of painkillers.
AB  - BACKGROUND: Aspirin (ASA) or non-aspirin-like nonsteroidal anti-inflammatory
      drugs (NSAIDs) influence platelet (PLT) function by inhibiting cyclooxygenase
      enzymes. In this study, the aim was to address the use of ASA or NSAIDs before
      donation and the effect on PLT function. STUDY DESIGN AND METHODS: Donors were
      asked questions about recent use of ASA or NSAIDs. Furthermore, PLT function was
      evaluated by measurement of the closure time (CT) in a PLT function analyzer (PFA
      100, Dade Behring) and by aggregometry (response to ADP or arachidonic acid
      [AA]). RESULTS: Of 100 questioned donors, 22 percent had used ASA (n = 4), NSAIDs
      (n = 6), or paracetamol (n = 12) before donation. Upon assessment of the PLT
      function in the PFA-100, 27 donors showed values of greater than 180 seconds,
      indicative of impaired PLT function. Of these, only 7 had used pain killers
      before donation. Furthermore, 15 of 22 users had normal CTs. Aggregation after
      stimulation with AA was absent in 33 PLT-rich samples. Again only 8 had reported
      use of ASA (3), NSAIDs (1), or paracetamol (4). Of the 22 users, 14 had normal AA
      aggregation responses. All donor samples showed ADP-induced aggregation,
      indicating PLT integrity. There was no difference between the group of donors who
      reported the intake of ASA or NSAIDs and the group of donors who did not with
      respect to the tested PLT function assays. CONCLUSION: It is concluded that there
      is a considerable group of donors that use PLT-influencing medication before
      donation. A relation between the reported use and impaired PLT function in blood
      donors could not be established, however. Impaired PLT function as tested may
      have other causes than intake of ASA or NSAIDs.

PMID- 17207233
TI  - Anti-hepatits B core antigen testing, viral markers, and occult hepatitis B virus
      infection in Pakistani blood donors: implications for transfusion practice.
AB  - BACKGROUND: The purpose of this study was to determine the seroprevalence of anti
      hepatitis B core antigen (HBc) and the impact of its testing along with other
      markers of hepatitis B, hepatitis B virus (HBV) DNA, hepatitis C virus antibody
      (anti-HCV), and syphilis in Pakistani blood donors. STUDY DESIGN AND METHODS: The
      study design was cross-sectional. A total of 966 donors were selected randomly
      for testing of anti-HBc and HBV markers, including HBV DNA, of 94,177 blood
      donors who were routinely screened for hepatitis B surface antigen (HBsAg), anti
      HCV, human immunodeficiency virus antibody (anti-HIV), Treponema pallidum
      hemagglutination assay (TPHA), and malarial parasites from 2003 to October 2005.
      RESULTS: The seroprevalence of various infectious markers was as follows: HBsAg,
      2.16 percent; anti-HCV, 4.16 percent; anti-HIV, 0.004 percent; TPHA, 0.75
      percent; and malaria, 0.002 percent. Anti-HBc prevalence in HBsAg-negative, HBV
      DNA-negative blood donors was 167 of 966 (17.28%), with 76 percent demonstrating
      anti-HBs positivity. Younger donors with mean age of 25 years were exposed to HBV
      to a lesser extent compared to those with a mean age of 29 years. Anti-HBc
      positivity was significantly higher in anti-HCV-reactive individuals. HBV DNA was
      detectable in 5 blood donors who were HBsAg-, anti-HBc-positive and were
      categorized as having occult HBV infection. CONCLUSIONS: The study shows that
      more than 17 percent of healthy, young blood donors in Pakistan are already
      exposed to HBV, with two-thirds showing anti-HBs levels of greater than 100 mIU
      per mL. One in 200 blood donors who are HBsAg-, anti-HBc-positive, however, have
      occult HBV infection, with likelihood of transmission of hepatitis B in
      recipients of blood components derived from them. HBsAg-negative individuals who
      are anti-HBc-negative and those who are anti-HBc-positive, anti-HBs-positive, and
      HBV DNA-negative should be selected as regular blood donors to minimize
      transmission due to occult hepatitis B infection.

PMID- 17207234
TI  - False-reactive microbiologic screening test results in Swedish blood donors-how
      big is the problem? A survey among blood centers and deferred donors.
AB  - BACKGROUND: Screening of blood donors for markers of transfusion-transmissible
      infectious agents leads to a varying number of false-reactive test results and
      sometimes thereby temporary or permanent deferral of donors and also to loss of
      collected units. STUDY DESIGN AND METHODS: Data on false-reactive screening test
      results in 2002 and 2003 were collected from 19 blood centers in Sweden. A
      questionnaire was sent to donors deferred because of false-reactive screening
      test results to investigate their perception of the information and their
      reaction to the deferral. RESULTS: Testing of 21,189 samples from new donors and
      423,543 donations from regular and/or repeat donors produced 1,059 false-reactive
      test results, mostly from hepatitis C virus antibody testing, and 299 deferrals.
      Six different human immunodeficiency virus tests led to between 0.02 and 0.2
      percent false-reactive results. The deferral rate varied considerably between
      different counties. Of 204 deferred donors contacted, 180 (88%) answered the
      questionnaire. More than 80 percent were worried about their test results and
      worry was more common among those who did not feel sufficiently informed.
      CONCLUSION: The results imply that there is a need for a more standardized
      approach to the screening of blood donors and donations with the aim of
      minimizing the number of false-reactive screening test results. They also
      emphasize the importance of appropriate information and support to deferred
      donors.

PMID- 17207236
TI  - Human immunodeficiency virus-1 subtypes and antiretroviral drug resistance
      profiles among drug-naive Brazilian blood donors.
AB  - BACKGROUND: Human immunodeficiency virus-1 (HIV-1) genetic variability and its
      implication on the development of new reagents were investigated by correlating
      time of infection and resistance to antiretroviral drugs. STUDY DESIGN AND
      METHODS: Seventy-four plasma samples from Brazilian drug-naive blood donors were
      assayed to further develop a panel of biologic reagents to be used in serology
      and molecular tests. After viral RNA extraction, cDNA was generated and used in
      nested polymerase chain reaction protocols with primers for the ENV (C2-V3 and
      gp41), protease (PR), and reverse transcriptase (RT) of HIV-1. Genomic sequencing
      was conducted to define HIV-1 subtypes and drug resistance mutations. RESULTS:
      Subtype B was found in 83.8 percent of all samples, subtype F in 2.7 percent, and
      BF mosaics in 11 percent of the cases. B and F different genetic profiles were
      evidenced: B(PR)B(RT)B(gp120)B(gp41), F(PR)F(RT)F(gp120)F(gp41),
      F(PR)F(RT)B(gp120)B(gp41), F(PR)B(RT)B(gp120)B(gp41), and
      B(PR)B(RT)F(gp120)B(gp41). A single sample (1.4%) was characterized as a BC
      mosaic (B(PR)C(RT)U(gp120)C(gp41)) and an AGH mosaic (AG(PR)G(RT)H(gp120)H(gp41))
      was first observed in the country. Antiretroviral resistance to nucleoside RT
      inhibitor was observed in one sample (1.35%) showing M41L and T215S mutations.
      Nonnucleoside RT inhibitor and major PR inhibitor resistance mutations were not
      observed. Previously unseen patterns of resistance to T20 were found among HIV-1
      infected drug-naive individuals in Brazil. Recent infections were characterized
      in 21.6 percent of the blood donor samples included in this study. CONCLUSIONS:
      The availability of characterized plasma samples and HIV isolates will allow the
      development of biologic reagents necessary to implement quality control programs
      and to develop, validate, and evaluate the performance of diagnostic kits,
      considering all HIV-1-circulating variants in the country.

PMID- 17207235
TI  - Evaluation of a new enzyme-linked immunosorbent assay for detection of Chagas
      antibody in US blood donors.
AB  - BACKGROUND: Chagas disease, caused by the parasite Trypanosoma cruzi, represents
      a serious blood safety problem due to increasing immigration from Latin America.
      The Food and Drug Administration recently recommended implementation of Chagas
      antibody screening for US donors as soon as a suitable assay is licensed. An
      anonymized preclinical study of a prototype T. cruzi lysate-based enzyme-linked
      immunosorbent assay (ELISA) developed by Ortho-Clinical Diagnostics was
      conducted. STUDY DESIGN AND METHODS: Two populations of specimens were evaluated:
      1) 10,192 sequential donations from blood donors residing in the El Paso, Texas,
      area and 2) 178 specimens from South America which were presumptively positive
      for antibodies to T. cruzi and purchased from commercial vendors. RESULTS: A
      total of 10,189 (99.97%) of the 10,192 screened donor specimens did not react,
      whereas 3 (0.03%) tested initially reactive. The 3 initially reactive specimens
      tested repeat reactive and were confirmed by radioimmunoprecipitation analysis
      (RIPA). Based on antibody profile analysis, 2 of the 3 Chagas-positive specimens
      were from the same donor. Observed specificity of the test was therefore 100
      percent. Of the specimens from South America, 173 of 178 were reactive by the
      prototype ELISA. Of the 5 nonreactive specimens, all did not react by indirect
      fluorescence assay, but 4 were positive by RIPA. Therefore, calculated
      sensitivity of the ELISA was 97.7 percent (173/177). CONCLUSIONS: These studies
      indicate that the prototype ELISA has excellent sensitivity and specificity for
      detection of antibodies to T. cruzi in donors. Moreover, among donations from a
      geographically selected collection region of the United States, observed
      seroprevalence was 0.03 percent.

PMID- 17207237
TI  - Monitoring survival and function of transfused platelets in Bernard-Soulier
      syndrome by flow cytometry and a cone and plate(let) analyzer (Impact-R).
AB  - BACKGROUND: Bernard-Soulier syndrome (BSS) patients may repeatedly require
      transfusion of platelets (PLTs). The hemostatic competence of transfused PLTs
      requires monitoring. STUDY DESIGN AND METHODS: Flow cytometry and a cone and
      plate(let) analyzer (Impact-R, DiaMed) were used to monitor survival and function
      of transfused PLTs in a 7-year-old girl with BSS undergoing surgery. Flow
      cytometry was applied to differentiate autologous PLTs from transfused PLTs by
      staining for CD42b. The Impact, which measures PLT adhesion and aggregation in
      response to high shear stress, was used to evaluate PLT function. RESULTS:
      Transfused PLTs were detectable by flow cytometry for 1 week after transfusion.
      While the patient's PLTs did not respond to high shear stress before transfusion,
      a normal response was documented by the Impact on the day after transfusion and 1
      week thereafter. CONCLUSION: Transfused PLTs were detectable by flow cytometry,
      and their functional activity was demonstrated by the Impact.

PMID- 17207238
TI  - Predictors of response and relapse in a cohort of adults with thrombotic
      thrombocytopenic purpura-hemolytic uremic syndrome: a single-institution
      experience.
AB  - BACKGROUND: Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP
      HUS) is a diagnosis of exclusion when a patient presents with the sine qua non
      findings of thrombocytopenia and microangiopathic hemolytic anemia without an
      identifiable cause. Although most patients respond to therapeutic plasma exchange
      (TPE), a significant number of patients relapse. The aim was to determine if
      clinical, laboratory, and/or treatment features could predict response and/or
      relapse. STUDY DESIGN AND METHODS: This study was a retrospective review of
      adults with TTP-HUS treated with TPE at our institution from January 1996 to
      February 2004. RESULTS: The study population consisted of 90 patients (69%
      female) with mean age of 45 years and mostly obese (65%). The majority of cases
      were considered idiopathic. Ten patients died (11%) from the disease before
      achieving a response, whereas 79 percent were considered responders. Obesity and
      severe anemia at presentation were predictors of response to TPE (p = 0.0126 and
      p = 0.0071, respectively). Among the responders, 28 percent relapsed in a median
      of 14 months. Male sex, severe thrombocytopenia (mean +/- SD, 13 x 10(9) +/- 8 x
      10(9)/L), and higher lactate dehydrogenase pre-/posttreatment ratio were
      associated with relapse (p values of 0.0141, 0.0199, and 0.0407, respectively).
      ADAMTS-13 values were not obtained on enough number of patients to provide
      important data. CONCLUSION: Although patient and laboratory characteristics
      associated with response and relapse were identified, there was significant
      overlap between patient groups. Thus, our findings offer preliminary evidence and
      do not yet justify short- or long-term changes in the management of patients with
      TTP-HUS.

PMID- 17207239
TI  - Outpatient high-dose melphalan in multiple myeloma patients.
AB  - BACKGROUND: The brief period of neutropenia and limited nonmarrow toxicity after
      high-dose melphalan (HDM) provide a rationale for outpatient treatment. STUDY
      DESIGN AND METHODS: Our experience with HDM (140-200 mg/m(2)) in 90 consecutive
      transplant episodes was retrospectively reviewed. Most patients were treated in
      an outpatient setting. Patients without a primary care provider (PCP) were
      electively admitted before the anticipated onset of neutropenia. Ceftriaxone was
      added to ciprofloxacin at the onset of neutropenia. All febrile patients were
      admitted. RESULTS: The median time from peripheral blood progenitor cell infusion
      to onset of neutropenia was 5 days (range, 4-6 days), and the mean duration of
      neutropenia was 5 days (range, 4-7 days). Thirty-eight transplants (42%) were
      performed entirely in the outpatient setting. The mean duration of
      hospitalization was 2.2 days in patients not electively admitted. The use of
      ceftriaxone was associated with a decreased risk for fever (39% vs. 79%) and
      reduced duration of hospitalization (1.6 days vs. 4.5 days) for nonelectively
      admitted patients. There was no treatment-related mortality. CONCLUSION:
      Ambulatory therapy with HDM is safe and can be achieved in a general outpatient
      setting. The predictable time to neutropenia allows even poor candidates for
      outpatient therapy to be admitted electively on Day +4. The apparent beneficial
      effect of ceftriaxone needs to be confirmed in randomized trials.

PMID- 17207240
TI  - Comparison and stability of ADAMTS13 activity in therapeutic plasma products.
AB  - BACKGROUND: The von Willebrand factor (VWF)-cleaving protease, ADAMTS13, is often
      deficient in cases of thrombotic thrombocytopenic purpura (TTP). The primary
      treatment of TTP is therapeutic plasma exchange (TPE) utilizing a variety of
      plasma products that help restore ADAMTS13 activity. However, multiple
      replacement products are available to choose from. Thawed plasma products have a
      variable refrigerated shelf life depending on the product type; stability of
      ADAMTS13 in thawed products stored at 1 to 6 degrees C has not been determined.
      STUDY DESIGN AND METHODS: ADAMTS13 activity was measured in three types of plasma
      products and cryoprecipitate. Fresh-frozen plasma (FFP) aliquots and
      cryoprecipitate-poor plasma (CPP) products were produced from 10 whole-blood (WB)
      donations. Twenty-four-hour plasma products were manufactured from 10 additional
      WB donations. ADAMTS13 activity in these products at time of thaw and after 5
      days of storage at 1 to 6 degrees C was measured with a modified version of the
      FRETS-VWF73 fluorogenic assay. ADAMTS13 activity at time of thaw was measured in
      10 units of cryoprecipitate and five related CPP products. RESULTS: ADAMTS13 is
      present in similar amounts in FFP, CPP, and 24-hour plasma products. Storage at 1
      to 6 degrees C for up to 5 days did not significantly diminish ADAMTS13 activity.
      The concentration of ADAMTS13 in cryoprecipitate was significantly higher than
      that observed in plasma products. CONCLUSION: FFP, CPP, and 24-hour plasma
      products should be equally effective for ADAMTS13 restoration through TPE and
      should remain so for the duration of the shelf life of the thawed products.

PMID- 17207241
TI  - Evaluation of platelet activation and cytokine release during storage of platelet
      concentrates processed from buffy coats either manually or by the automated
      OrbiSac system.
AB  - BACKGROUND: This study aimed to compare platelet (PLT) quality during storage of
      buffy coat (BC) PLT concentrates (PCs), prepared either manually or by the
      automated OrbiSac system (Gambro BCT). STUDY DESIGN AND METHODS: Following
      overnight storage at 20 to 22 degrees C, five BCs were pooled with 300 mL of PLT
      additive solution. Twenty-one PCs were produced manually (M-PCs) and 21 by the
      automated OrbiSac system (A-PCs). Swirling, PLT count, mean PLT volume, blood gas
      analyses, potassium, glucose, and lactate were assessed. Expression of the
      activation markers CD42a, CD62P, and PAC-1 was analyzed by flow cytometry on
      resting PLTs and PLTs stimulated with thrombin receptor agonist peptide (TRAP).
      Levels of CCL5 and transforming growth factor-beta1 (TGF-beta1) were measured by
      enzyme-linked immunosorbent assay. RESULTS: The A-PCs had significantly larger
      volume and higher PLT yield, PLT recovery, and white blood cell concentration
      than the M-PCs, whereas the red blood cell content was significantly highest in
      the M-PCs. pH levels were between 6.9 and 7.2 in all PCs. Neither glucose
      consumption nor lactate production differed significantly over time. A-PCs had,
      compared to M-PCs, significantly higher expression of CD62P on resting PLTs,
      lower capacity for up regulating CD62P on TRAP-stimulated PLTs, and higher levels
      of CCL5 during storage. TRAP-stimulated A-PCs had a significantly higher
      potential for down regulation of CD42a than M-PCs. No difference was found in TGF
      beta1 levels or TRAP-induced up regulation of PAC-1. CONCLUSION: The levels of
      CCL5 and the expression of CD62P in resting and stimulated PLTs indicate that
      PLTs in A-PCs are slightly more activated than in M-PCs, but the clinical
      importance of this finding is yet unknown.

PMID- 17207242
TI  - The molecular diversity of Sema7A, the semaphorin that carries the JMH blood
      group antigens.
AB  - BACKGROUND: Semaphorin 7A (Sema7A), the protein that carries the JMH blood group
      antigen, is involved in immune responses and plays an important role in axon
      growth and guidance. Because previous serologic studies on red blood cells (RBCs)
      suggested a considerable diversity of Sema7A, the present study was designed to
      elucidate the complex picture of the molecular diversity of this protein. STUDY
      DESIGN AND METHODS: The JMH antigen status was determined by serology, flow
      cytometry, and Western blot. Genomic and transcript analysis of SEMA7A was
      performed by nucleotide sequencing. Recombinant Sema7A proteins were used for
      genotype-phenotype correlation. A three-dimensional model of Sema7A was generated
      for topologic analyses. RESULTS: Our studies on 44 individuals with unusual JMH
      phenotypes and their family members revealed that aberrant Sema7A expression can
      be an inherited or an acquired phenomenon and is based on reduced surface
      expression or qualitative changes in Sema7A. These different phenotypes are
      caused by variations of the SEMA7A gene or seem to be generated by autoimmune
      related or RBC lineage-specific mechanisms. The variant JMH phenotypes were
      related to the presence of missense mutations in SEMA7A, predicting amino acid
      changes in the semaphorin domain of Sema7A. Sequence analysis of the variant
      SEMA7A alleles revealed mutations affecting codons 207 and 460/461. Topologic
      analyses showed that Sema7A polymorphisms were prominently located on the top and
      bottom of the semaphorin domain, suggesting a functional relevance of these
      sites. CONCLUSION: These findings provide a basis with which to delineate the
      various ligand-binding surfaces of Sema7A.

PMID- 17207243
TI  - Knops blood group haplotypes among distinct Brazilian populations.
AB  - BACKGROUND: The Knops blood group system consists of antigens encoded by exon 29
      of complement receptor 1 (CR1) gene. To better elucidate the complexity of Knops
      group system, the frequency of six single-nucleotide polymorphisms (SNPs) in
      three Brazilian populations is determined. STUDY DESIGN AND METHODS: A total of
      118 individuals descendant from Europe, Asia, and Africa were studied. The
      genomic fragment of CR1 was amplified by polymerase chain reaction, and the SNPs
      and haplotypes were determined after DNA sequence analysis. RESULTS: Among the
      six polymorphisms characterized, one of them was described for the first time.
      The analysis of allele frequency showed that these six SNPs did not differ
      between the European and Asian groups. The African group presented a higher
      frequency of alleles McC(b), Sl2, and KAM+. The six polymorphisms gave origin to
      12 haplotypes that were defined for the first time. The haplotypes 1 (4646A,
      Kn(a), McC(a), Sl1, Sl4, KAM+), 2 (4646A, Kn(a), McC(a), Sl1, KAM-), and 3
      (4646A, Kn(a), McC(a), Sl2, Sl4, KAM-) are the most frequent in all populations.
      The H2 presents similar frequency in all populations; however, whereas the H1
      presented a higher prevalence in the European and Asian groups, in the African
      group H3 was present in a higher prevalence. CONCLUSIONS: In this study, a new
      SNP substituting serine for asparagine at amino acid 1540 was identified.
      Moreover 12 haplotypes were identified. The differences in haplotype frequencies
      strongly suggest that the H1 and H2 might be the ancestral one while the H3 may
      have originated in Africa and may have fixed there by positive selection.

PMID- 17207244
TI  - Generation of inflammatory cytokines and chemokines from peripheral blood
      mononuclear cells by HLA Class II antibody-containing plasma unit that was
      associated with severe nonhemolytic transfusion reactions.
AB  - BACKGROUND: HLA Class II antibodies are thought to be involved in severe
      transfusion reactions including transfusion-related acute lung injury (TRALI).
      The activation of monocytes by HLA Class II antibody may play an important role
      in the etiology of TRALI. CASE REPORT: An 81-year-old man with non-Hodgkin's
      lymphoma (Clinical Stage IIIA) received a plateletpheresis unit containing at
      least 4 x 10(11) platelets because of thrombocytopenia and a bleeding tendency.
      Approximately 30 minutes after the start of transfusion, he developed chills,
      tachycardia, dyspnea, lumber, and abdominal pain and then a fever (40.3 degrees
      C). His SaO(2) dropped to 70 percent. The transfusion was discontinued
      immediately. His symptoms disappeared after treatment with oxygen and the
      administration of corticosteroid and aminophyrine. A chest X-ray showed no sign
      of pulmonary edema. RESULTS: The donor serum sample had HLA-DR antibodies against
      multiple DR antigens including DR13, the recipient's HLA-DR type. The cross-match
      between the patient's lymphocytes and the donor serum was positive. The treatment
      of peripheral blood mononuclear cells from healthy subjects bearing DR13 antigen
      with the donor plasma caused the secretion of inflammatory cytokines (i.e.,
      interleukin [IL]-1beta, IL-6, and tumor necrosis factor-alpha) and neutrophil
      activating chemokines (i.e., IL-8 and CXCL1/GRO-alpha) in a cognate antigen
      antibody relationship. In addition, the secretion of inflammatory cytokines
      appeared to require the involvement of CD32 and/or CD16. CONCLUSION: HLA-DR
      antibodies, detected in this case, had biologic functions to induce production of
      not only inflammatory cytokines but also neutrophil-attractant chemokines in
      vitro, which could contribute to the etiology of severe nonhemolytic transfusion
      reactions.

PMID- 17207245
TI  - Characterization of blood-borne transmission of simian foamy virus.
AB  - BACKGROUND: Simian foamy virus (SFV) is an endemic, nonhuman primate (NHP)
      retrovirus that is transmitted to individuals who work with or hunt NHPs. The
      cross-species transmission of simian retroviruses is believed to be the etiology
      of human immunodeficiency virus and human T-lymphotropic virus infections in
      humans. Although SFV is not pathogenic in the native host, the shared ancestry
      with other simian retroviruses has brought into question the potential for
      acquired pathogenicity after cross-species transmission. This study examines
      whether SFV also shares the traits of transmissibility through the blood supply.
      STUDY DESIGN AND METHODS: Within a controlled environment, blood from an SFV
      infected monkey was transfused into an SFV-uninfected monkey. Evidence of
      infection, pathogenic effects, immune correlates, and viral shedding were
      followed for 6 months after transfusion. RESULTS: Molecular evidence of SFV
      infection manifested 8 weeks after transfusion followed by seroconversion 1 week
      later. Quantitative analysis demonstrated that the highest level of detectable
      virus was concomitant with seroconversion followed by establishment of a viral
      "set-point." Analysis of circulating lymphocytes revealed changes early in
      infection. Potential routes of transmission of SFV and roles of site-specific
      immune response are suggested by the late appearance of SFV shedding in the
      saliva of the transfused animal. CONCLUSION: The blood supply has historically
      provided a portal through which novel, occult viruses can become disseminated
      among humans. The demonstration of transmissibility of SFV through whole-blood
      transfusion, in an NHP model, contributes to the understanding of potential risks
      associated with blood donation by SFV-infected humans.

PMID- 17207246
TI  - Transfusion-related acute lung injury and transfusion-associated circulatory
      overload: mutually exclusive or coexisting entities?

PMID- 17207247
TI  - Prevalence of antibodies to lymphocytic choriomeningitis virus in blood donors in
      southeastern France.

PMID- 17207248
TI  - Preventing transfusion-associated graft-versus-host disease.

PMID- 17207252
TI  - Approaches to achieve high-level heterologous protein production in plants.
AB  - Plants offer an alternative to microbial fermentation and animal cell cultures
      for the production of recombinant proteins. For protein pharmaceuticals, plant
      systems are inherently safer than native and even recombinant animal sources. In
      addition, post-translational modifications, such as glycosylation, which cannot
      be achieved with bacterial fermentation, can be accomplished using plants. The
      main advantage foreseen for plant systems is reduced production costs. Plants
      should have a particular advantage for proteins produced in bulk, such as
      industrial enzymes, for which product pricing is low. In addition, edible plant
      tissues are well suited to the expression of vaccine antigens and pharmaceuticals
      for oral delivery. Three approaches have been followed to express recombinant
      proteins in plants: expression from the plant nuclear genome; expression from the
      plastid genome; and expression from plant tissues carrying recombinant plant
      viral sequences. The most important factor in moving plant-produced heterologous
      proteins from developmental research to commercial products is to ensure
      competitive production costs, and the best way to achieve this is to boost
      expression. Thus, considerable research effort has been made to increase the
      amount of recombinant protein produced in plants. This research includes
      molecular technologies to increase replication, to boost transcription, to direct
      transcription in tissues suited for protein accumulation, to stabilize
      transcripts, to optimize translation, to target proteins to subcellular locations
      optimal for their accumulation, and to engineer proteins to stabilize them. Other
      methods include plant breeding to increase transgene copy number and to utilize
      germplasm suited to protein accumulation. Large-scale commercialization of plant
      produced recombinant proteins will require a combination of these technologies.

PMID- 17207253
TI  - Engineering of a sialic acid synthesis pathway in transgenic plants by expression
      of bacterial Neu5Ac-synthesizing enzymes.
AB  - Plants are a low-cost and contamination-free factory for the production of
      recombinant pharmaceutical proteins. However, plant-made pharmaceuticals differ
      from their mammalian homologues by the structure of their N-linked glycans. For
      instance, most mammalian glycoproteins harbour terminal sialic acids that control
      their half-life in the bloodstream. The absence of the whole sialylation
      machinery in plants is of major concern as non-sialylated plant-made
      pharmaceuticals may not perform at their full potential in humans, because of
      their removal from the circulation through the involvement of hepatic cell
      receptors. In this context, we have investigated the synthesis of N
      acetylneuraminic acid (Neu5Ac) in the cytosol of plants by either the re-routing
      of the endogenous 3-deoxy-d-manno-2-octulosonic acid (Kdo) biosynthetic pathway
      or the expression of microbial Neu5Ac-synthesizing enzymes. In this paper, we
      demonstrate that the plant Kdo-8P synthase is not able to use N-acetyl d
      mannosamine as a substrate, and thus re-routing of the Kdo pathway for the
      synthesis of Neu5Ac is not possible. Consequently, we expressed genes encoding
      Neu5Ac lyase from Escherichia coli and Neu5Ac synthase (neuB2) from Campylobacter
      jejuni in plants. These resulted in the production of functional enzymes in the
      cytosol, which in turn can catalyse the synthesis of Neu5Ac in vitro. Experiments
      were carried out on two models, Bright Yellow 2 (BY2) tobacco cells and Medicago
      sativa (alfalfa), the perennial legume crop.

PMID- 17207254
TI  - Increasing morphinan alkaloid production by over-expressing codeinone reductase
      in transgenic Papaver somniferum.
AB  - Only plants of the Papaver genus (poppies) are able to synthesize morphinan
      alkaloids, and cultivation of P. somniferum, opium poppy, remains critical for
      the production and supply of morphine, codeine and various semi-synthetic
      analgesics. Opium poppy was transformed with constitutively expressed cDNA of
      codeinone reductase (PsCor1.1), the penultimate step in morphine synthesis. Most
      transgenic lines showed significant increases in capsule alkaloid content in
      replicated glasshouse and field trials over 4 years. The morphinan alkaloid
      contents on a dry weight basis were between 15% and 30% greater than those in
      control high-yielding genotypes and control non-transgenic segregants. Transgenic
      leaves had approximately 10-fold greater levels of Cor transcript compared with
      non-transgenic controls. Two cycles of crossing of the best transgenic line into
      an elite high-morphine genotype resulted in significant increases in morphine and
      total alkaloids relative to the elite recurrent parent. No significant changes in
      alkaloid profiles or quantities were observed in leaf, roots, pollen and seed.

PMID- 17207255
TI  - Microarray analysis of Fusarium graminearum-induced wheat genes: identification
      of organ-specific and differentially expressed genes.
AB  - A wheat cDNA microarray consisting of 5739 expressed sequence tags (ESTs) was
      used to investigate the transcriptome patterns of the glume, lemma, palea,
      anther, ovary and rachis dissected from infected wheat spikes after inoculation
      with the fungus Fusarium graminearum, the causal agent of fusarium head blight
      (FHB) disease. Stringent conditions were employed to reduce the false discovery
      rate. The significance analysis of microarrays (SAM) was used to identify
      transcripts that showed a differential response between fungal-challenged vs.
      control plants. To verify the microarray data, Northern blot analysis was carried
      out on randomly selected up-regulated clones. We observed 185 (3.2%) up-regulated
      and 16 (0.28%) down-regulated ESTs in the six organs constituting the wheat
      spike. Many up-regulated ESTs (46.67%) showed no homology with sequences of known
      functions, whereas others showed homology with genes involved in defence and
      stress responses, the oxidative burst of H(2)O(2), regulatory functions, protein
      synthesis and the phenylpropanoid pathway. The monitoring of genes in specific
      organs avoided the averaging of expression values over multiple organs that
      occurs when using data from the whole spike. Our data allowed us to uncover new
      up-regulated genes expressed in specific organs. The study revealed that each
      organ had a defined and distinctive transcriptome pattern in response to F.
      graminearum infection.

PMID- 17207256
TI  - Therapeutic effectiveness of orally administered transgenic low-alkaloid tobacco
      expressing human interleukin-10 in a mouse model of colitis.
AB  - Inflammatory bowel disease (IBD) represents a spectrum of diseases in which
      inflammation leads to acute and chronic gut injury. It is a growing health issue
      for which no cure exists. The pathogenesis is multifactorial with links to
      infectious and environmental events that trigger disease in genetically
      predisposed individuals. Treatment of the two major forms of IBD, Crohn's disease
      and ulcerative colitis, involves the reduction of inflammation with toxic
      immunosuppressive drugs or blocking of the pro-inflammatory effects of tumour
      necrosis factor-alpha (TNF-alpha) with antibodies. Here, we show that the oral
      administration of transgenic low-alkaloid tobacco expressing the contra
      inflammatory cytokine human interleukin-10 (hIL-10) reduces the severity of
      colitis by down-regulating TNF-alpha expression directly at the sites of
      inflammation in IBD-susceptible IL-10(-/-) mice. hIL-10 expressed in plants is
      biologically active and displays resistance to gastrointestinal degradation.
      Dietary supplementation with plant tissue delivering up to 9 microg of hIL-10
      daily for 4 weeks was well tolerated by treated mice. Gut histology was
      significantly improved relative to controls (P = 0.002), and was correlated with
      a decrease in small bowel TNF-alpha mRNA levels and an increase in IL-2 and IL
      1beta mRNA levels. Transgenic plants expressing IL-10 to directly attenuate TNF
      alpha expression at sites of inflammation in the gut may become a useful new
      approach in the luminal therapy of IBD.

PMID- 17207257
TI  - Varietal effects of eight paired lines of transgenic Bt maize and near-isogenic
      non-Bt maize on soil microbial and nematode community structure.
AB  - A glasshouse experiment was undertaken to provide baseline data on the variation
      between conventional maize (Zea mays L.) varieties and genetically modified maize
      plants expressing the insecticidal Bacillus thuringiensis protein (Bt, Cry1Ab).
      The objective was to determine whether the variation in soil parameters under a
      range of conventional maize cultivars exceeded the differences between Bt and non
      Bt maize cultivars. Variations in plant growth parameters (shoot and root
      biomass, percentage carbon, percentage nitrogen), Bt protein concentration in
      shoots, roots and soil, soil nematode abundance and soil microbial community
      structure were determined. Eight paired varieties (i.e. varieties genetically
      modified to express Bt protein and their near-isogenic control varieties) were
      investigated, together with a Bt variety for which no near-isogenic control was
      available (NX3622, a combined transformant expressing both Bt and herbicide
      tolerance) and a conventional barley (Hordeum vulgare L.) variety which was
      included as a positive control. The only plant parameter which showed a
      difference between Bt varieties and near-isogenic counterparts was the shoot
      carbon to nitrogen ratio; this was observed for only two of the eight varieties,
      and so was not attributable to the Bt trait. There were no detectable differences
      in the concentration of Bt protein in plant or soil with any of the Bt-expressing
      varieties. There were significant differences in the abundance of soil nematodes,
      but this was not related to the Bt trait. Differences in previously published
      soil nematode studies under Bt maize were smaller than these varietal effects.
      Soil microbial community structure, as determined by phospholipid fatty acid
      (PLFA) analysis, was strongly affected by plant growth stage but not by the Bt
      trait. The experimental addition of purified Cry1Ab protein to soil confirmed
      that, at ecologically relevant concentrations, there were no measurable effects
      on microbial community structure.

PMID- 17207258
TI  - SAGE of the developing wheat caryopsis.
AB  - Understanding the development of the cereal caryopsis holds the future for
      metabolic engineering in the interests of enhancing global food production. We
      have developed a Serial Analysis of Gene Expression (SAGE) data platform to
      investigate the developing wheat (Triticum aestivum) caryopsis. LongSAGE
      libraries have been constructed at five time-points post-anthesis to coincide
      with key processes in caryopsis development. More than 90,000 LongSAGE tags have
      been sequenced generating 29,261 unique tag sequences across all five libraries.
      Tag abundance, generated from cumulative tag counts, provides insight into the
      redundancy and diversity of each library. Annotation of the 500 most abundant
      tags spanning development highlights the array of functional groups being
      expressed. The relative frequency of these more abundant transcripts allows
      quantitative analysis of patterns of expression during grain development. We have
      identified activities of cellular proliferation/differentiation, the accumulation
      of storage proteins and starch biosynthesis. The abundance of calcium-dependent
      protein kinases indicate their importance in signalling across development.
      Acquisition of a broad array of defence coincides with storage accumulation and
      is dominated by inhibitors of amylase activity. Differential expression profiles
      of abundant tags from each library reveal the coordinated expression of genes
      responsible for the cellular events constituting caryopsis development. This SAGE
      platform has also provided a resource of novel sequence and expression
      information including the identification of potentially useful promoter
      activities. Further investigations into both the abundant and low expressing
      transcripts will provide greater insight into wheat caryopsis development and
      assist in wheat improvement programmes.

PMID- 17207259
TI  - Endosperm tissue is good production platform for artificial recombinant proteins
      in transgenic rice.
AB  - Transgenic rice plants expressing 7Crp peptide were generated by Agrobacterium
      mediated transformation. The 7Crp peptide is the hybrid peptide of seven major
      human T-cell epitopes derived from Japanese cedar pollen allergens Cry j 1 and
      Cry j 2. When the 7Crp gene was expressed under the control of the rice AGPase
      large subunit or maize ubiquitin-1 promoters, it could only be detected in the
      endosperm of rice seed, although high levels of RNA transcript were observed in
      the leaf, stem, and seed embryo. It was demonstrated by confocal and electron
      microscopy analysis that the 7Crp peptide was mainly localized in the endoplasmic
      reticulum-derived protein bodies, designated protein body I (PB-I). Our results
      indicate that rice endosperm tissue has advantage over other tissues as a
      production platform for foreign recombinant proteins.

PMID- 17207260
TI  - Suspension-cultured BY-2 tobacco cells produce and mature immunologically active
      house dust mite allergens.
AB  - The replacement of crude allergen extracts by selected allergens currently
      represents a major goal for the improvement of allergy diagnosis and
      immunotherapy. Indeed, the development of molecularly defined vaccines would
      facilitate both standardization and enhance batch-to-batch reproducibility as
      well as treatment specificity. In this study, we have investigated the potential
      of tobacco plant cells to produce biologically active forms of the two major
      allergens from the house dust mite. A detailed characterization of these plant
      made allergens has shown similar proteolytic maturation and folding as well as
      comparable immunoreactivity to their natural counterparts. Altogether, our
      results exemplify that suspension-cultured BY-2 tobacco cells represent a low
      cost and environmentally safe expression system suitable to produce recombinant
      allergens from Dermatophagoides pteronyssinus under a form appropriate for
      diagnostic and therapeutic purposes.

PMID- 17207261
TI  - Doubled sugar content in sugarcane plants modified to produce a sucrose isomer.
AB  - Sucrose is the feedstock for more than half of the world's fuel ethanol
      production and a major human food. It is harvested primarily from sugarcane and
      beet. Despite attempts through conventional and molecular breeding, the stored
      sugar concentration in elite sugarcane cultivars has not been increased for
      several decades. Recently, genes have been cloned for bacterial isomerase enzymes
      that convert sucrose into sugars which are not metabolized by plants, but which
      are digested by humans, with health benefits over sucrose. We hypothesized that
      an appropriate sucrose isomerase (SI) expression pattern might simultaneously
      provide a valuable source of beneficial sugars and overcome the sugar yield
      ceiling in plants. The introduction of an SI gene tailored for vacuolar
      compartmentation resulted in sugarcane lines with remarkable increases in total
      stored sugar levels. The high-value sugar isomaltulose was accumulated in storage
      tissues without any decrease in stored sucrose concentration, resulting in up to
      doubled total sugar concentrations in harvested juice. The lines with enhanced
      sugar accumulation also showed increased photosynthesis, sucrose transport and
      sink strength. This remarkable step above the former ceiling in stored sugar
      concentration provides a new perspective into plant source-sink relationships,
      and has substantial potential for enhanced food and biofuel production.

PMID- 17207262
TI  - Generation and characterization of soybean and marker-free tobacco plastid
      transformants over-expressing a bacterial 4-hydroxyphenylpyruvate dioxygenase
      which provides strong herbicide tolerance.
AB  - Plant 4-hydroxyphenylpyruvate dioxygenase (HPPD) is part of the biosynthetic
      pathway leading to plastoquinone and vitamin E. This enzyme is also the molecular
      target of various new bleaching herbicides for which genetically engineered
      tolerant crops are being developed. We have expressed a sensitive bacterial hppd
      gene from Pseudomonas fluorescens in plastid transformants of tobacco and soybean
      and characterized in detail the recombinant lines. HPPD accumulates to
      approximately 5% of total soluble protein in transgenic chloroplasts of both
      species. As a result, the soybean and tobacco plastid transformants acquire a
      strong herbicide tolerance, performing better than nuclear transformants. In
      contrast, the over-expression of HPPD has no significant impact on the vitamin E
      content of leaves or seeds, quantitatively or qualitatively. A new strategy is
      presented and exemplified in tobacco which allows the rapid generation of
      antibiotic marker-free plastid transformants containing the herbicide tolerance
      gene only. This work reports, for the first time, the plastome engineering for
      herbicide tolerance in a major agronomic crop, and a technology leading to marker
      free lines for this trait.

PMID- 17207263
TI  - Expression of an engineered granule-bound Escherichia coli maltose
      acetyltransferase in wild-type and amf potato plants.
AB  - Starch is used in many industrial applications, but often requires chemical
      derivatization to enhance its properties before use. In particular, the stability
      of starch polymers in solution is improved by acetylation. A drawback of this
      treatment is the use of pollutant chemicals. A biological alternative to chemical
      derivatization was investigated by the expression of an amyloplast-targeted
      Escherichia coli maltose acetyltransferase (MAT) gene in tubers of wild-type
      (Kardal) and mutant amylose-free (amf) potato plants. MAT was expressed as such,
      or fused to the N- or C-terminus of a non-catalytic starch-binding domain (SBD)
      to target the starch granule. Starch granules derived from transgenic plants were
      found to contain acetyl groups, although their content was low, opening up an
      avenue to move away from the post-harvest chemical derivatization of starch. MAT
      inside starch granules was found to be active post-harvest when supplied with
      acetyl-coenzyme A and glucose or maltose, but it did not acetylate starch
      polymers in vitro. Starch granules from transformants in which MAT alone was
      expressed also showed MAT activity, indicating that MAT is accumulated in starch
      granules, and has affinity for starch by itself. Furthermore, starch granule
      morphology was altered, and fusion proteins containing MAT and SBD seemed to have
      a higher affinity for starch granules than two appended SBDs. These results are
      discussed against the background of the quaternary structure of MAT.

PMID- 17207264
TI  - Transcriptome analysis reveals season-specific rbcS gene expression profiles in
      diploid perennial ryegrass (Lolium perenne L.).
AB  - Perennial ryegrass (Lolium perenne L.) is a major grass species used for forage
      and turf throughout the world, and gains by conventional breeding have reached a
      plateau. Perennial ryegrass is an outcrossing, self-incompatible diploid (2n = 2x
      = 14) with a relatively large genome (4067 Mbp/diploid genome; Evans, G.M., Rees,
      H., Snell, C.L. and Sun, S. (1972) The relation between nuclear DNA amount and
      the duration of the mitotic cycle. Chrom. Today, 3, 24-31). Using tissues sourced
      from active pastures during the peak of the autumn, winter, spring and summer
      seasons, we analysed the ryegrass transcriptome employing a Serial Analysis of
      Gene Expression (SAGE) protocol, with the dual goals of understanding the
      seasonal changes in perennial ryegrass gene expression and enhancing our ability
      to select genes for genetic manipulation. A total of 159,002 14-mer SAGE tags was
      sequenced and mapped to the perennial ryegrass DNA database, comprising methyl
      filtered (GeneThresher) and expressed sequence tag (EST) sequences. The analysis
      of 14,559 unique SAGE tags, which were present more than once in our SAGE
      library, revealed 964, 1331, 346 and 131 exclusive transcripts to autumn, winter,
      spring and summer, respectively. Intriguingly, our analysis of the SAGE tags
      revealed season-specific expression profiles for the small subunit of ribulose
      1,5-bisphosphate carboxylase (Rubisco), LprbcS. The transcript level for LprbcS
      was highest in spring, and then decreased gradually between summer and winter.
      Five different copies of LprbcS were revealed in ryegrass, with one possibly
      producing splice variant transcripts. Two highly expressed LprbcS genes were
      reported, one of which was not active in autumn. Another LprbcS gene showed an
      inverse expression profile to the autumn inactive LprbcS in a manner to
      compensate the expression level.

PMID- 17207265
TI  - Production of polyhydroxybutyrate in sugarcane.
AB  - We report here the production of the bacterial polyester, polyhydroxybutyrate
      (PHB), in the crop species sugarcane (Saccharum spp. hybrids). The PHB
      biosynthesis enzymes of Ralstonia eutropha [beta-ketothiolase (PHAA), acetoacetyl
      reductase (PHAB) and PHB synthase (PHAC)] were expressed in the cytosol or
      targeted to mitochondria or plastids. PHB accumulated in cytosolic lines at trace
      amounts, but was not detected in mitochondrial lines. In plastidic lines, PHB
      accumulated in leaves to a maximum of 1.88% of dry weight without obvious
      deleterious effects. Epifluorescence and electron microscopy of leaf sections
      from these lines revealed that PHB granules were visible in plastids of most cell
      types, except mesophyll cells. The concentration of PHB in culm internodes of
      plastidic lines was substantially lower than in leaves. Western blot analysis of
      these lines indicated that expression of the PHB biosynthesis proteins was not
      limiting in culm internodes. Epifluorescence microscopy of culm internode
      sections from plastidic lines showed that PHB granules were visible in most cell
      types, except photosynthetic cortical cells in the rind, and that the lower PHB
      concentration in culm internodes was probably a result of dilution of PHB
      containing cells by the large number of cells with little or no PHB. We discuss
      strategies for producing PHB in mitochondria and mesophyll cell plastids, and for
      increasing PHB yields in culms.

PMID- 17207266
TI  - Spatio-temporal characterization of polyhydroxybutyrate accumulation in
      sugarcane.
AB  - We report here the results from a glasshouse trial of several transgenic
      sugarcane (Saccharum spp. hybrids) lines accumulating the bacterial polyester
      polyhydroxybutyrate (PHB) in plastids. The aims of the trial were to characterize
      the spatio-temporal pattern of PHB accumulation at a whole-plant level, to
      identify factors limiting PHB production and to determine whether agronomic
      performance was affected adversely by PHB accumulation. Statistical analysis
      showed that a vertical PHB concentration gradient existed throughout the plant,
      the polymer concentration being lowest in the youngest leaves and increasing with
      leaf age. In addition, there was a horizontal gradient along the length of a
      leaf, with the PHB concentration increasing from the youngest part of the leaf
      (the base) to the oldest (the tip). The rank order of the lines did not change
      over time. Moreover, there was a uniform spatio-temporal pattern of relative PHB
      accumulation among the lines, despite the fact that they showed marked
      differences in absolute PHB concentration. Molecular analysis revealed that the
      expression of the transgenes encoding the PHB biosynthesis enzymes was apparently
      coordinated, and that there were good correlations between PHB concentration and
      the abundance of the PHB biosynthesis enzymes. The maximum recorded PHB
      concentration, 1.77% of leaf dry weight, did not confer an agronomic penalty. The
      plant height, total aerial biomass and culm-internode sugar content were not
      affected relative to controls. Although moderate PHB concentrations were achieved
      in leaves, the maximum total-plant PHB yield was only 0.79% (11.9 g PHB in 1.51
      kg dry weight). We combine the insights from our statistical and molecular
      analyses to discuss possible strategies for increasing the yield of PHB in
      sugarcane.

PMID- 17207267
TI  - Formation of the indigo precursor indican in genetically engineered tobacco
      plants and cell cultures.
AB  - The production of the blue dye indigo in plants has been assumed to be a possible
      route to the introduction of novel coloration into flowers or fibres. As the
      human cytochrome P450 mono-oxygenase 2A6 (CYP2A6) can form indigo in bacterial
      cultures, we investigated whether the expression of the corresponding cDNA in
      transgenic plants could lead to indigo formation. In a first attempt, we
      generated tobacco cell suspension cultures expressing the cDNA encoding human
      CYP2A6. Supplementation of the medium with indole led to the generation of
      indican (3-hydroxyindole-beta-d-glucoside), a metabolite usually exclusively
      present in indigoferous dye plants. Hence, the recombinant CYP2A6 converted
      indole to the reactive metabolite 3-hydroxyindole (indoxyl), whereas rapid
      glucosylation is obviously conducted by ubiquitous plant glucosyl transferases
      (GTs). Interestingly, of nine additionally tested plant cell suspension cultures
      from various plant families, five were also capable of the formation of indican
      after indole supplementation, although this metabolism was more pronounced in
      transgenic tobacco cell suspension cultures expressing CYP2A6 cDNA. To evaluate
      whether indican or even indigo could be produced in whole plants, we generated
      transgenic tobacco plants harbouring active CYP2A6 together with an indole
      synthase (BX1) from maize. The genetically engineered tobacco plants accumulated
      indican, but did not develop a blue coloration. Although the de novo formation of
      indican in transgenic tobacco plants hampered indigo formation, it supports the
      contention that biosynthetic pathways can be efficiently mimicked by metabolic
      engineering.

PMID- 17207268
TI  - Transcriptome analysis of senescence in the flag leaf of wheat (Triticum aestivum
      L.).
AB  - The senescence process in wheat flag leaves was investigated over a time course
      from ear emergence until 50% yellowing of harvested leaf samples using an in
      house fabricated cDNA microarray based on a 9K wheat unigene set. The top 1000
      ranked differentially expressed probes were subjected to a cluster analysis and,
      from these, we selected 140 up-regulated genes with informative annotations.
      There was a considerable overlap between this list of genes and genes previously
      observed to be associated with senescence in other species, covering several
      functional categories involved in the degradation of macromolecules and nutrient
      remobilization, notably of nitrogen via the metabolism of carboxylic and amino
      acids. The up-regulation of a number of genes in this metabolism was confirmed by
      real-time polymerase chain reaction experiments. The data suggest a role for
      cytosolic/peroxisomal routes in the integration of the degradation of
      carbohydrates, fatty acids and proteins, leading to the remobilization of
      nitrogen. Illustrative examples of up-regulated genes comprise cytoplasmic
      aconitate hydratase and peroxisomal citrate synthase. The data support a
      protective role of the mitochondria towards oxidative cell damage via the up
      regulation of the alternative oxidase, and possibly also involving the up
      regulated succinate dehydrogenase. A number of up-regulated regulatory genes were
      also identified, notably NAC-domain and WRKY transcription factors. These factors
      have previously been identified as being associated with senescence in other
      species. The data support the notion that a generic senescence programme exists
      across monocot and dicot plant species. However, notable differences can also be
      recognized. We thus found transcriptional up-regulation of the biosynthetic
      pathway for benzoxazinoids, a group of graminaceous-specific secondary
      metabolites.

PMID- 17207270
TI  - Regulation of spindle orientation and neural stem cell fate in the Drosophila
      optic lobe.
AB  - BACKGROUND: The choice of a stem cell to divide symmetrically or asymmetrically
      has profound consequences for development and disease. Unregulated symmetric
      division promotes tumor formation, whereas inappropriate asymmetric division
      affects organ morphogenesis. Despite its importance, little is known about how
      spindle positioning is regulated. In some tissues cell fate appears to dictate
      the type of cell division, whereas in other tissues it is thought that stochastic
      variation in spindle position dictates subsequent sibling cell fate. RESULTS:
      Here we investigate the relationship between neural progenitor identity and
      spindle positioning in the Drosophila optic lobe. We use molecular markers and
      live imaging to show that there are two populations of progenitors in the optic
      lobe: symmetrically dividing neuroepithelial cells and asymmetrically dividing
      neuroblasts. We use genetically marked single cell clones to show that
      neuroepithelial cells give rise to neuroblasts. To determine if a change in
      spindle orientation can trigger a neuroepithelial to neuroblast transition, we
      force neuroepithelial cells to divide along their apical/basal axis by
      misexpressing Inscuteable. We find that this does not induce neuroblasts, nor
      does it promote premature neuronal differentiation. CONCLUSION: We show that
      symmetrically dividing neuroepithelial cells give rise to asymmetrically dividing
      neuroblasts in the optic lobe, and that regulation of spindle orientation and
      division symmetry is a consequence of cell type specification, rather than a
      mechanism for generating cell type diversity.

PMID- 17207271
TI  - VaxiJen: a server for prediction of protective antigens, tumour antigens and
      subunit vaccines.
AB  - BACKGROUND: Vaccine development in the post-genomic era often begins with the in
      silico screening of genome information, with the most probable protective
      antigens being predicted rather than requiring causative microorganisms to be
      grown. Despite the obvious advantages of this approach--such as speed and cost
      efficiency--its success remains dependent on the accuracy of antigen prediction.
      Most approaches use sequence alignment to identify antigens. This is problematic
      for several reasons. Some proteins lack obvious sequence similarity, although
      they may share similar structures and biological properties. The antigenicity of
      a sequence may be encoded in a subtle and recondite manner not amendable to
      direct identification by sequence alignment. The discovery of truly novel
      antigens will be frustrated by their lack of similarity to antigens of known
      provenance. To overcome the limitations of alignment-dependent methods, we
      propose a new alignment-free approach for antigen prediction, which is based on
      auto cross covariance (ACC) transformation of protein sequences into uniform
      vectors of principal amino acid properties. RESULTS: Bacterial, viral and tumour
      protein datasets were used to derive models for prediction of whole protein
      antigenicity. Every set consisted of 100 known antigens and 100 non-antigens. The
      derived models were tested by internal leave-one-out cross-validation and
      external validation using test sets. An additional five training sets for each
      class of antigens were used to test the stability of the discrimination between
      antigens and non-antigens. The models performed well in both validations showing
      prediction accuracy of 70% to 89%. The models were implemented in a server, which
      we call VaxiJen. CONCLUSION: VaxiJen is the first server for alignment
      independent prediction of protective antigens. It was developed to allow antigen
      classification solely based on the physicochemical properties of proteins without
      recourse to sequence alignment. The server can be used on its own or in
      combination with alignment-based prediction methods. It is freely-available
      online at the URL: http://www.jenner.ac.uk/VaxiJen.

PMID- 17207272
TI  - Pathways as "signatures in landscape": towards an ethnography of mobility among
      the Mbya-Guarani (Northeastern Argentina).
AB  - Processes of spatial mobility among the Mbya are of interest in anthropological
      and ethnobiological studies, as these processes are related to transformations in
      the landscape and the environment. Despite this, ethnographic literature usually
      focuses itself on the mobility of Guarani communities from the perspective of
      population dynamics on a regional scale. Our research among two Mbya-Guarani
      communities in the Argentinean province of Misiones has enabled us to recognize
      patterns of mobility on a micro-scale. Certainly, the mobility of adult members
      of these communities as they perform hunting and gathering activities delimit
      spaces of individual use. We consider the different pathways as "signatures in
      landscape", resulting from processes of spatial mobility inherent to those
      activities. Taking into account the gathering and circulation of medicinal plants
      for treatment of gastrointestinal illnesses, we have been able to identify
      different pathways inherent in their search, towards the monte or other spaces
      away from de settlement. The design and construction of the pathways is
      determined by the specific personal knowledge of individuals who search for these
      valuable resources. Using both strategies of direct observation--as members of
      the community manipulate different resources during these search and gathering
      trips--and interviews, we have been able to gather and interpret significant
      information on the strategies used by the Mbya to domesticate the monte areas. As
      a consequence of our approach we suggest that the landscape design resulting from
      these trips should not be considered a consensual or collective strategy of the
      whole community; it is rather the result of the daily strategies of individuals,
      which involves the selection of resources mainly based on each individual's
      knowledge and interests.

PMID- 17207273
TI  - Comparison of plants used for skin and stomach problems in Trinidad and Tobago
      with Asian ethnomedicine.
AB  - This paper provides a preliminary evaluation of fifty-eight ethnomedicinal plants
      used in Trinidad and Tobago for skin problems, stomach problems, pain and
      internal parasites for safety and possible efficacy. Thirty respondents, ten of
      whom were male were interviewed from September 1996 to September 2000 on
      medicinal plant use for health problems. The respondents were obtained by
      snowball sampling, and were found in thirteen different sites, 12 in Trinidad and
      one in Tobago. The uses are compared to those current in Asia. Bambusa vulgaris,
      Bidens alba, Jatropha curcas, Neurolaena lobata, Peperomia rotundifolia and
      Phyllanthus urinaria are possibly efficacious for stomach problems, pain and
      internal parasites. Further scientific study of these plants is warranted.

PMID- 17207274
TI  - Quality of life and salivary output in patients with head-and-neck cancer five
      years after radiotherapy.
AB  - BACKGROUND: To describe long-term changes in time of quality of life (QOL) and
      the relation with parotid salivary output in patients with head-and-neck cancer
      treated with radiotherapy. METHODS: Forty-four patients completed the EORTC-QLQ
      C30(+3) and the EORTC-QLQ-H&N35 questionnaires before treatment, 6 weeks, 6
      months, 12 months, and at least 3.5 years after treatment. At the same time
      points, stimulated bilateral parotid flow rates were measured. RESULTS: There was
      a deterioration of most QOL items after radiotherapy compared with baseline, with
      gradual improvement during 5 years follow-up. The specific xerostomia-related
      items showed improvement in time, but did not return to baseline. Global QOL did
      not alter significantly in time, although 41% of patients complained of moderate
      or severe xerostomia at 5 years follow-up. Five years after radiotherapy the mean
      cumulated parotid flow ratio returned to baseline but 20% of patients had a flow
      ratio <25%. The change in time of xerostomia was significantly related with the
      change in flow ratio (p = 0.01). CONCLUSION: Most of the xerostomia-related QOL
      scores improved in time after radiotherapy without altering the global QOL, which
      remained high. The recovery of the dry mouth feeling was significantly correlated
      with the recovery in parotid flow ratio.

PMID- 17207275
TI  - Effect of pioglitazone treatment on behavioral symptoms in autistic children.
AB  - INTRODUCTION: Autism is complex neuro-developmental disorder which has a
      symptomatic diagnosis in patients characterized by disorders in
      language/communication, behavior, and social interactions. The exact causes for
      autism are largely unknown, but is has been speculated that immune and
      inflammatory responses, particularly those of Th2 type, may be involved.
      Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator activated
      receptor gamma (PPARgamma), a nuclear hormone receptor which modulates insulin
      sensitivity, and have been shown to induce apoptosis in activated T-lymphocytes
      and exert anti-inflammatory effects in glial cells. The TZD pioglitazone (Actos)
      is an FDA-approved PPARgamma agonist used to treat type 2 diabetes, with a good
      safety profile, currently being tested in clinical trials of other neurological
      diseases including AD and MS. We therefore tested the safety and therapeutic
      potential of oral pioglitazone in a small cohort of children with diagnosed
      autism. CASE DESCRIPTION: The rationale and risks of taking pioglitazone were
      explained to the parents, consent was obtained, and treatment was initiated at
      either 30 or 60 mg per day p.o. A total of 25 children (average age 7.9 +/- 0.7
      year old) were enrolled. Safety was assessed by measurements of metabolic
      profiles and blood pressure; effects on behavioral symptoms were assessed by the
      Aberrant Behavior Checklist (ABC), which measures hyperactivity, inappropriate
      speech, irritability, lethargy, and stereotypy, done at baseline and after 3-4
      months of treatment. DISCUSSION AND EVALUATION: In a small cohort of autistic
      children, daily treatment with 30 or 60 mg p.o. pioglitazone for 3-4 months
      induced apparent clinical improvement without adverse events. There were no
      adverse effects noted and behavioral measurements revealed a significant decrease
      in 4 out of 5 subcategories (irritability, lethargy, stereotypy, and
      hyperactivity). Improved behaviors were inversely correlated with patient age,
      indicating stronger effects on the younger patients. CONCLUSION: Pioglitazone
      should be considered for further testing of therapeutic potential in autistic
      patients.

PMID- 17207276
TI  - HSV-2- and HIV-1- permissive cell lines co-infected by HSV-2 and HIV-1 co
      replicate HSV-2 and HIV-1 without production of HSV-2/HIV-1 pseudotype particles.
AB  - BACKGROUND: Herpes simplex virus type 2 (HSV-2) is a major cofactor of human
      immunodeficiency virus type 1 (HIV-1) sexual acquisition and transmission. In the
      present study, we investigated whether HIV-1 and HSV-2 may interact at the
      cellular level by forming HIV-1 hybrid virions pseudotyped with HSV-2 envelope
      glycoproteins, as was previously reported for HSV type 1. METHODS: We evaluated
      in vitro the production of HSV-2/HIV-1 pseudotypes in mononuclear CEM cells and
      epithelial HT29 and P4P cells. We analyzed the incorporation into the HIV-1
      membrane of HSV-2 gB and gD, two major HSV-2 glycoproteins required for HSV-2
      fusion with the cell membrane, in co-infected cells and in HIV-1-infected P4P
      cells transfected by plasmids coding for gB or gD. RESULTS: We show that HSV-2
      and HIV-1 co-replicated in dually infected cells, and gB and gD were co-localized
      with gp160. However, HIV-1 particles, produced in HIV-1-infected cells expressing
      gB or gD after transfection or HSV-2 superinfection, did not incorporate either
      gB or gD in the viral membrane, and did not have the capacity to infect cells
      normally non-permissive for HIV-1, such as epithelial cells. CONCLUSION: Our
      results do not support the hypothesis of HSV-2/HIV-1 pseudotype formation and
      involvement in the synergistic genital interactions between HIV-1 and HSV-2.

PMID- 17207277
TI  - Clinical relevance of neutral endopeptidase (NEP/CD10) in melanoma.
AB  - BACKGROUND: Overexpression of Neutral Endopeptidase (NEP) has been reported in
      metastatic carcinomas, implicating NEP in tumor progression and suggesting a role
      for NEP inhibitors in its treatment. We investigated the role of NEP expression
      in the clinical progression of cutaneous melanoma. METHODS: We screened 7
      melanoma cell lines for NEP protein expression. NEP-specific siRNA was
      transfected into the lines to examine the role of gene transcription in NEP
      expression. Immunohistochemistry was done for 93 specimens and correlated with
      clinicopathologic parameters. Thirty-seven metastatic melanoma specimens were
      examined for NEP transcript expression using Affymetrix GeneChips. In a subset of
      25 specimens for which both transcript and protein expression was available,
      expression ratios were used to identify genes that co-express with NEP in
      GeneChip analysis. RESULTS: NEP was overexpressed in 4/7 human melanoma cell
      lines, and siRNA knock-down of NEP transcripts led to downregulation of its
      protein expression. NEP protein overexpression was significantly more common in
      metastatic versus primary tumors (P = 0.002). Twelve of 37 (32%) metastatic
      tumors had increased NEP transcript expression, and an association was observed
      between NEP transcript upregulation and protein overexpression (P < 0.0001).
      Thirty-eight genes were found to significantly co-express with NEP (p < 0.005).
      Thirty-three genes positively correlated with NEP, including genes involved in
      the MAP kinase pathway, antigen processing and presentation, apoptosis, and WNT
      signaling pathway, and 5 genes negatively correlated with NEP, including genes of
      focal adhesion and the notch signaling pathways. CONCLUSION: NEP overexpression,
      which seems to be largely driven by increased transcription, is rare in primary
      melanoma and occurs late in melanoma progression. Functional studies are needed
      to better understand the mechanisms of NEP regulation in melanoma.

PMID- 17207278
TI  - Motives and preferences of general practitioners for new collaboration models
      with medical specialists: a qualitative study.
AB  - BACKGROUND: Collaboration between general practitioners (GPs) and specialists has
      been the focus of many collaborative care projects during the past decade.
      Unfortunately, quite a number of these projects failed. This raises the question
      of what motivates GPs to initiate and continue participating with medical
      specialists in new collaborative care models. The following two questions are
      addressed in this study: What motivates GPs to initiate and sustain new models
      for collaborating with medical specialists? What kind of new collaboration models
      do GPs suggest? METHODS: A qualitative study design was used. Starting in 2003
      and finishing in 2005, we conducted semi-structured interviews with a purposive
      sample of 21 Dutch GPs. The sampling criteria were age, gender, type of practice,
      and practice site. The interviews were recorded, fully transcribed, and analysed
      by two researchers working independently. The resulting motivational factors and
      preferences were grouped into categories. RESULTS: 'Developing personal
      relationships' and 'gaining mutual respect' appeared to dominate when the
      motivational factors were considered. Besides developing personal relationships
      with specialists, the GPs were also interested in familiarizing specialists with
      the competencies attached to the profession of family medicine. Additionally,
      they were eager to increase their medical knowledge to the benefit of their
      patients. The GPs stated a variety of preferences with respect to the design of
      new models of collaboration. CONCLUSION: Developing personal relationships with
      specialists appeared to be one of the dominant motives for increased
      collaboration. Once the relationships have been formed, an informal network with
      occasional professional contact seemed sufficient. Although GPs are interested in
      increasing their knowledge, once they have reached a certain level of expertise,
      they shift their focus to another specialty. The preferences for new
      collaboration models are diverse. A possible explanation for the differences in
      the preferences is that professionals are more knowledge driven than organisation
      driven as the acquiring of new knowledge is considered more important than the
      route by which this is achieved. A new collaboration model seems a way to acquire
      knowledge. Once this is achieved the importance of a model possibly diminishes,
      whereas the professional relationships last.

PMID- 17207279
TI  - Green tea increases anti-inflammatory tristetraprolin and decreases pro
      inflammatory tumor necrosis factor mRNA levels in rats.
AB  - BACKGROUND: Tristetraprolin (TTP/ZFP36) family proteins have anti-inflammatory
      activity by binding to and destabilizing pro-inflammatory mRNAs such as Tnf mRNA,
      and represent a potential therapeutic target for inflammation-related diseases.
      Tea has anti-inflammatory properties but the molecular mechanisms have not been
      completely elucidated. We hypothesized that TTP and/or its homologues might
      contribute to the beneficial effects of tea as an anti-inflammatory product.
      METHODS: Quantitative real-time PCR was used to investigate the effects of green
      tea (0, 1, and 2 g solid extract/kg diet) on the expression of Ttp family genes
      (Ttp/Tis11/Zfp36, Zfp36l1/Tis11b, Zfp36l2/Tis11d, Zfp36l3), pro-inflammatory
      genes (Tnf, Csf2/Gm-csf, Ptgs2/Cox2), and Elavl1/Hua/Hur and Vegf genes in liver
      and muscle of rats fed a high-fructose diet known to induce insulin resistance,
      oxidative stress, inflammation, and TNF-alpha levels. RESULTS: Ttp and Zfp36l1
      mRNAs were the major forms in both liver and skeletal muscle. Ttp, Zfp36l1, and
      Zfp36l2 mRNA levels were more abundant in the liver than those in the muscle.
      Csf2/Gm-csf and Zfp36l3 mRNAs were undetectable in both tissues. Tea (1 g solid
      extract/kg diet) increased Ttp mRNA levels by 50-140% but Tnf mRNA levels
      decreased by 30% in both tissues, and Ptgs2/Cox2 mRNA levels decreased by 40% in
      the muscle. Tea (2 g solid extract/kg diet) increased Elavl1/Hua/Hur mRNA levels
      by 40% in the liver but did not affect any of the other mRNA levels in liver or
      muscle. CONCLUSION: These results show that tea can modulate Ttp mRNA levels in
      animals and suggest that a post-transcriptional mechanism through TTP could
      partially account for tea's anti-inflammatory properties. The results also
      suggest that drinking adequate amounts of green tea may play a role in the
      prevention of inflammation-related diseases.

PMID- 17207280
TI  - Qualitative and quantitative differences between taste buds of the rat and mouse.
AB  - BACKGROUND: Numerous electrophysiological, ultrastructural, and
      immunocytochemical studies on rodent taste buds have been carried out on rat
      taste buds. In recent years, however, the mouse has become the species of choice
      for molecular and other studies on sensory transduction in taste buds. Do rat and
      mouse taste buds have the same cell types, sensory transduction markers and
      synaptic proteins? In the present study we have used antisera directed against
      PLCbeta2, alpha-gustducin, serotonin (5-HT), PGP 9.5 and synaptobrevin-2 to
      determine the percentages of taste cells expressing these markers in taste buds
      in both rodent species. We also determined the numbers of taste cells in the
      taste buds as well as taste bud volume. RESULTS: There are significant
      differences (p < 0.05) between mouse and rat taste buds in the percentages of
      taste cells displaying immunoreactivity for all five markers. Rat taste buds
      display significantly more immunoreactivity than mice for PLCbeta2 (31.8% vs
      19.6%), alpha-gustducin (18% vs 14.6%), and synaptobrevin-2 (31.2% vs 26.3%).
      Mice, however, have more cells that display immunoreactivity to 5-HT (15.9% vs
      13.7%) and PGP 9.5 (14.3% vs 9.4%). Mouse taste buds contain an average of 85.8
      taste cells vs 68.4 taste cells in rat taste buds. The average volume of a mouse
      taste bud (42,000 microm3) is smaller than a rat taste bud (64,200 microm3). The
      numerical density of taste cells in mouse circumvallate taste buds (2.1
      cells/1000 microm3) is significantly higher than that in the rat (1.2 cells/1000
      microm3). CONCLUSION: These results suggest that rats and mice differ
      significantly in the percentages of taste cells expressing signaling molecules.
      We speculate that these observed dissimilarities may reflect differences in their
      gustatory processing.

PMID- 17207281
TI  - Growth of the protozoan parasite Entamoeba histolytica in 5-azacytidine has
      limited effects on parasite gene expression.
AB  - BACKGROUND: In higher eukaryotes DNA methylation regulates important biological
      functions including silencing of gene expression and protection from adverse
      effects of retrotransposons. In the protozoan parasite Entamoeba histolytica, a
      DNA methyltransferase has been identified and treatment with 5-azacytidine (5
      AzaC), a potent inhibitor of DNA methyltransferase, has been reported to
      attenuate parasite virulence. However, the overall extent of DNA methylation and
      its subsequent effects on global gene expression in this parasite are currently
      unknown. RESULTS: In order to identify the genome-wide effects of DNA methylation
      in E. histolytica, we used a short oligonucleotide microarray representing 9,435
      genes (approximately 95% of all annotated amebic genes) and compared the
      expression profile of E. histolytica HM-1:IMSS parasites with those treated with
      23 microM 5-AzaC for up to one week. Overall, 2.1% of genes tested were
      transcriptionally modulated under these conditions. 68 genes were upregulated and
      131 genes down regulated (2-fold change; p-value < 0.05). Sodium-bisulfite
      treatment and sequencing of genes indicated that there were at least two subsets
      of genes with genomic DNA methylation in E. histolytica: (i) genes that were
      endogenously silenced by genomic DNA methylation and for which 5-AzaC treatment
      induced transcriptional de-repression, and (ii) genes that have genomic DNA
      methylation, but which were not endogenously silenced by the methylation. We
      identified among the genes down regulated by 5-AzaC treatment a cysteine
      proteinase (2.m00545) and lysozyme (52.m00148) both of which have known roles in
      amebic pathogenesis. Decreased expression of these genes in the 5-AzaC treated E.
      histolytica may account in part for the parasites reduced cytolytic abilities.
      CONCLUSION: This work represents the first genome-wide analysis of DNA
      methylation in Entamoeba histolytica and indicates that DNA methylation has
      relatively limited effects on gene expression in this parasite.

PMID- 17207283
TI  - Revival of the side-to-side approach for distal coronary anastomosis.
AB  - Side-to-side anastomosis was employed by just ten proportional stitches while
      performing distal anastomosis during coronary artery surgery. This technique is
      simple and quick. Here this simple technique is described in detail and the
      postoperative status of grafted conduits is reported.

PMID- 17207282
TI  - Amaranth oil application for coronary heart disease and hypertension.
AB  - Cardiovascular disease (CVD) is the Nation's leading killer for both men and
      women among all racial and ethnic groups. Development and progression of CVD is
      linked to the presence of risk factors such as hyperlipidemia, hypertension,
      obesity, and diabetes mellitus. It is known that cholesterol is an indicator of
      increased risk of heart attack and stroke. Low-density cholesterol (LDL) above
      130 mg/dl high-density cholesterol (HDL) cholesterol below 35 mg/dl and total
      blood cholesterol above 200 mg/dl are indicators of problematic cholesterol.
      Proper ranges of cholesterol are important in the prevention of CVD. It has been
      suggested that a reduction in the consumption of saturated and an increase in
      unsaturated fatty acids is beneficial and prevents CVD. Amaranth grain contains
      tocotrienols and squalene compounds, which are known to affect cholesterol
      biosynthesis. The cholesterol precursors squalene, lanosterol and other methyl
      sterols, reflect cholesterol synthesis 123, whereas plant sterols and
      cholestanol, a metabolite of cholesterol, reflect the efficiency of cholesterol
      absorption in normal and hyperlipidemic populations 456. Qureshi with co-authors
      7 showed that feeding of chickens with amaranth oil decreases blood cholesterol
      levels, which are supported by the work of others 8. Previously, we have shown
      that Amaranth oil modulates the cell membrane fluidity 9 and stabilized membranes
      that could be one reason as to why it is beneficial to those who consume it. It
      is known that in hypertension, the cell membrane is defective and hence, the
      movement of the Na and K ions across the cell membranes could defective that
      could contribute to the development of increase in blood pressure. Based on these
      properties of amaranth oil we hypothesize that it could be of significant benefit
      for patients with CVD.

PMID- 17207284
TI  - Discovering biomarkers from gene expression data for predicting cancer subgroups
      using neural networks and relational fuzzy clustering.
AB  - BACKGROUND: The four heterogeneous childhood cancers, neuroblastoma, non-Hodgkin
      lymphoma, rhabdomyosarcoma, and Ewing sarcoma present a similar histology of
      small round blue cell tumor (SRBCT) and thus often leads to misdiagnosis.
      Identification of biomarkers for distinguishing these cancers is a well studied
      problem. Existing methods typically evaluate each gene separately and do not take
      into account the nonlinear interaction between genes and the tools that are used
      to design the diagnostic prediction system. Consequently, more genes are usually
      identified as necessary for prediction. We propose a general scheme for finding a
      small set of biomarkers to design a diagnostic system for accurate classification
      of the cancer subgroups. We use multilayer networks with online gene selection
      ability and relational fuzzy clustering to identify a small set of biomarkers for
      accurate classification of the training and blind test cases of a well studied
      data set. RESULTS: Our method discerned just seven biomarkers that precisely
      categorized the four subgroups of cancer both in training and blind samples. For
      the same problem, others suggested 19-94 genes. These seven biomarkers include
      three novel genes (NAB2, LSP1 and EHD1 - not identified by others) with distinct
      class-specific signatures and important role in cancer biology, including
      cellular proliferation, transendothelial migration and trafficking of MHC class
      antigens. Interestingly, NAB2 is downregulated in other tumors including Non
      Hodgkin lymphoma and Neuroblastoma but we observed moderate to high upregulation
      in a few cases of Ewing sarcoma and Rabhdomyosarcoma, suggesting that NAB2 might
      be mutated in these tumors. These genes can discover the subgroups correctly with
      unsupervised learning, can differentiate non-SRBCT samples and they perform
      equally well with other machine learning tools including support vector machines.
      These biomarkers lead to four simple human interpretable rules for the diagnostic
      task. CONCLUSION: Although the proposed method is tested on a SRBCT data set, it
      is quite general and can be applied to other cancer data sets. Our scheme takes
      into account the interaction between genes as well as that between genes and the
      tool and thus is able find a very small set and can discover novel genes. Our
      findings suggest the possibility of developing specialized microarray chips or
      use of real-time qPCR assays or antibody based methods such as ELISA and western
      blot analysis for an easy and low cost diagnosis of the subgroups.

PMID- 17207285
TI  - FM1-43 is a permeant blocker of mechanosensitive ion channels in sensory neurons
      and inhibits behavioural responses to mechanical stimuli.
AB  - The molecular identity and pharmacological properties of mechanically gated ion
      channels in sensory neurons are poorly understood. We show that FM1-43, a styryl
      dye used to fluorescently label cell membranes, permeates mechanosensitive ion
      channels in cultured dorsal root ganglion neurons, resulting in blockade of three
      previously defined subtypes of mechanically activated currents. Blockade and dye
      uptake is voltage dependent and regulated by external Ca2+. The structurally
      related larger dye FM3-25 inhibited mechanically activated currents to a lesser
      degree and did not permeate the channels. In vivo, FMI-43 decreases pain
      sensitivity in the Randall-Selitto test and increases the withdrawal threshold
      from von Frey hairs, together suggesting that the channels expressed at the cell
      body in culture mediate mechanosensation in the intact animal. These data give
      further insight into the mechanosensitive ion channels expressed by somatosensory
      neurons and suggest FM dyes are an interesting tool for studying them.

PMID- 17207286
TI  - Evidence for recent gene flow between north-eastern and south-eastern Madagascan
      poison frogs from a phylogeography of the Mantella cowani group.
AB  - BACKGROUND: The genus Mantella, endemic poison frogs of Madagascar with 16
      described species, are known in the field of international pet trade and entered
      under the CITES control for the last four years. The phylogeny and phylogeography
      of this genus have been recently subject of study for conservation purposes. Here
      we report on the studies of the phylogeography of the Mantella cowani group using
      a fragment of 453 bp of the mitochondrial cytochrome b gene from 195 individuals
      from 21 localities. This group is represented by five forms: M. cowani, a
      critically endangered species, a vulnerable species, M. haraldmeieri, and the non
      threatened M. baroni, M. aff. baroni, and M. nigricans. RESULTS: The Bayesian
      phylogenetic and haplotype network analyses revealed the presence of three
      separated haplotype clades: (1) M. baroni, M. aff. baroni, M. nigricans, and
      putative hybrids of M. cowani and M. baroni, (2) M. cowani and putative hybrids
      of M. cowani and M. baroni, and (3) M. haraldmeieri. The putative hybrids were
      collected from sites where M. cowani and M. baroni live in sympatry. CONCLUSION:
      These results suggest (a) a probable hybridization between M. cowani and M.
      baroni, (b) a lack of genetic differentiation between M. baroni/M. aff. baroni
      and M. nigricans, (c) evidence of recent gene-flow between the northern (M.
      nigricans), eastern (M. baroni), and south-eastern (M. aff. baroni) forms of
      distinct coloration, and (d) the existence of at least three units for
      conservation in the Mantella cowani group.

PMID- 17207287
TI  - Detection of epithelial to mesenchymal transition in airways of a bleomycin
      induced pulmonary fibrosis model derived from an alpha-smooth muscle actin-Cre
      transgenic mouse.
AB  - BACKGROUND: Epithelial to mesenchymal transition (EMT) in alveolar epithelial
      cells (AECs) has been widely observed in patients suffering interstitial
      pulmonary fibrosis. In vitro studies have also demonstrated that AECs could
      convert into myofibroblasts following exposure to TGF-beta1. In this study, we
      examined whether EMT occurs in bleomycin (BLM) induced pulmonary fibrosis, and
      the involvement of bronchial epithelial cells (BECs) in the EMT. Using an alpha
      smooth muscle actin-Cre transgenic mouse (alpha-SMA-Cre/R26R) strain, we labelled
      myofibroblasts in vivo. We also performed a phenotypic analysis of human BEC
      lines during TGF-beta1 stimulation in vitro. METHODS: We generated the alpha-SMA
      Cre mouse strain by pronuclear microinjection with a Cre recombinase cDNA driven
      by the mouse alpha-smooth muscle actin (alpha-SMA) promoter. alpha-SMA-Cre mice
      were crossed with the Cre-dependent LacZ expressing strain R26R to produce the
      double transgenic strain alpha-SMA-Cre/R26R. beta-galactosidase (betagal)
      staining, alpha-SMA and smooth muscle myosin heavy chains immunostaining were
      carried out simultaneously to confirm the specificity of expression of the
      transgenic reporter within smooth muscle cells (SMCs) under physiological
      conditions. BLM-induced peribronchial fibrosis in alpha-SMA-Cre/R26R mice was
      examined by pulmonary betagal staining and alpha-SMA immunofluorescence staining.
      To confirm in vivo observations of BECs undergoing EMT, we stimulated human BEC
      line 16HBE with TGF-beta1 and examined the localization of the myofibroblast
      markers alpha-SMA and F-actin, and the epithelial marker E-cadherin by
      immunofluorescence. RESULTS: betagal staining in organs of healthy alpha-SMA
      Cre/R26R mice corresponded with the distribution of SMCs, as confirmed by alpha
      SMA and SM-MHC immunostaining. BLM-treated mice showed significantly enhanced
      betagal staining in subepithelial areas in bronchi, terminal bronchioles and
      walls of pulmonary vessels. Some AECs in certain peribronchial areas or even a
      small subset of BECs were also positively stained, as confirmed by alpha-SMA
      immunostaining. In vitro, addition of TGF-beta1 to 16HBE cells could also
      stimulate the expression of alpha-SMA and F-actin, while E-cadherin was
      decreased, consistent with an EMT. CONCLUSION: We observed airway EMT in BLM
      induced peribronchial fibrosis mice. BECs, like AECs, have the capacity to
      undergo EMT and to contribute to mesenchymal expansion in pulmonary fibrosis.

PMID- 17207288
TI  - Metastatic prostate cancer masquerading clinically and radiologically as a
      primary caecal carcinoma.
AB  - BACKGROUND: Prostatic carcinoma is the second most common cause of cancer-related
      deaths in males in the West. Approximately 20% of patients present with
      metastatic disease. We describe the case of a patient with metastatic prostate
      cancer to the bowel presenting clinically and radiologically as a primary caecal
      cancer. CASE PRESENTATION: A 72 year-old man presented with abdominal discomfort
      and a clinically palpable caecal mass and a firm nodule on his thigh, the latter
      behaving clinically and radiologically as a lipoma. Computed tomographic (CT)
      scan showed a luminally protuberant caecal mass with regional nodal involvement.
      The patient was being treated (Zoladex) for prostatic cancer diagnosed 6 years
      previously and was known to have bony metastases. On admission his PSA was 245.4
      nmol/ml. The patient underwent a right hemicolectomy. Histology showed a poorly
      differentiated adenocarcinoma which was PSA positive, confirming metastatic
      prostatic adenocarcinoma to the caecum. The patient underwent adjuvant
      chemotherapy and is free from recurrence a year later. CONCLUSION: Metastasis of
      prostatic carcinoma to the bowel is a very rare occurrence and presents a
      challenging diagnosis. The diagnosis is supported by immunohistochemistry for
      PSA. The treatment for metastatic prostate cancer is mainly palliative.

PMID- 17207289
TI  - Sex differences in judging self-orientation: the morphological horizon and body
      pitch.
AB  - BACKGROUND: Sex differences exist for many spatial tasks. This is true for
      circular vection, field dependence, and perception of veridical vertical with
      body tilt. However, explanations for these sex differences is lacking in the
      literature. In this study, we investigated the nature of individual differences
      in the perception of self-orientation in humans. Male and female participants
      were asked to identify their Morphological Horizon (i.e., line perpendicular to
      saggital plane at eye-level) in different body orientations relative to gravity
      (i.e., 45 deg and 135 deg body pitch) with and without prior whole body rotation.
      RESULTS: Sex explained the observed differences in the perception of self
      orientation only when blood distribution was least altered (i.e., 45 deg body
      pitch) and without prior whole body rotation. Specifically, females presented a
      more footward bias than males in these conditions. CONCLUSION: These results add
      to the literature on sex differences for spatial orientation tasks. As the
      differences were only observed with static conditions and when blood distribution
      was least affected, we concluded that sex differences in the perception of self
      orientation are associated with gravireceptors (e.g., otoliths).

PMID- 17207290
TI  - Methods for transient assay of gene function in floral tissues.
AB  - BACKGROUND: There is considerable interest in rapid assays or screening systems
      for assigning gene function. However, analysis of gene function in the flowers of
      some species is restricted due to the difficulty of producing stably transformed
      transgenic plants. As a result, experimental approaches based on transient gene
      expression assays are frequently used. Biolistics has long been used for
      transient over-expression of genes of interest, but has not been exploited for
      gene silencing studies. Agrobacterium-infiltration has also been used, but the
      focus primarily has been on the transient transformation of leaf tissue. RESULTS:
      Two constructs, one expressing an inverted repeat of the Antirrhinum majus
      (Antirrhinum) chalcone synthase gene (CHS) and the other an inverted repeat of
      the Antirrhinum transcription factor gene Rosea1, were shown to effectively
      induce CHS and Rosea1 gene silencing, respectively, when introduced biolistically
      into petal tissue of Antirrhinum flowers developing in vitro. A high-throughput
      vector expressing the Antirrhinum CHS gene attached to an inverted repeat of the
      nos terminator was also shown to be effective. Silencing spread systemically to
      create large zones of petal tissue lacking pigmentation, with transmission of the
      silenced state spreading both laterally within the affected epidermal cell layer
      and into lower cell layers, including the epidermis of the other petal surface.
      Transient Agrobacterium-mediated transformation of petal tissue of tobacco and
      petunia flowers in situ or detached was also achieved, using expression of the
      reporter genes GUS and GFP to visualise transgene expression. CONCLUSION: We
      demonstrate the feasibility of using biolistics-based transient RNAi, and
      transient transformation of petal tissue via Agrobacterium infiltration to study
      gene function in petals. We have also produced a vector for high throughput gene
      silencing studies, incorporating the option of using T-A cloning to insert the
      gene sequence of interest. These techniques should allow analysis of gene
      function in a much broader range of flower species.

PMID- 17207291
TI  - Tobacco use among students aged 13-15 years in Greece: the GYTS project.
AB  - BACKGROUND: Data on the prevalence of tobacco use among teenagers in Greece are
      limited. We examined the prevalence of smoking among middle-school students in
      Greece using the Global Youth Tobacco Survey (GYTS). METHODS: The Global Youth
      Tobacco Survey was implemented in Greece during the academic year 2004-2005 by
      the University of Thessaly and the National School of Public Health. Data were
      collected using the GYTS self-administered anonymous questionnaire, which was
      distributed by specifically trained field workers to a nationally representative
      sample of middle-school students aged 13-15 years (through randomly selected
      schools and classes), randomly selected through a two-stage cluster sample
      design. Data processing and statistical analyses were performed at the Centers
      for Disease Control and Prevention (CDC). RESULTS: About one third of the
      students 32.1% (29.4-35.0) reported that they had tried tobacco in the past,
      while 16.2% (14.3-18.4) reported being current users of tobacco products. In
      addition, 1 in 4 of ever smokers reported that they began smoking before the age
      of 10 years old. Almost 1 in 5 never smokers reported being susceptible to
      initiate smoking in the next year and about 89.8% (88.3-91.1) of the respondents
      were exposed to environmental tobacco smoke in their homes and 94.1% (93.2-94.9)
      in public places. Finally, a strikingly high number of students 95% (89.5-97.7)
      reported that they were able to buy their own cigarettes without restrictions.
      CONCLUSION: The results of the GYTS show that the prevalence of smoking in middle
      school children is alarmingly high in Greece. Smoking among young people
      constitutes a significant problem that is destined to worsen in the absence of
      any comprehensive efforts focused on strict anti-smoking legislation, policies
      and tobacco control interventions targeting children at a young age.

PMID- 17207292
TI  - Using lay counsellors to promote community-based voluntary counselling and HIV
      testing in rural northern Ghana: a baseline survey on community acceptance and
      stigma.
AB  - Access to voluntary counselling and HIV testing (VCT) remains limited in most
      parts of Ghana with rural populations being the least served. Services remain
      facility-based and employ the use of an ever-dwindling number of health workers
      as counsellors. This study assessed approval for the use of lay counsellors to
      promote community-based voluntary counselling and testing for HIV and the extent
      of HIV/AIDS-related stigma in the Kassena-Nankana district of rural northern
      Ghana. A cross-sectional questionnaire survey was conducted. Logistic regression
      was used to identify predictors of the tendency to stigmatize people living with
      HIV/AIDS (PLWHAs). Focus group discussions were held and analytical coding of the
      data performed. The majority (91.1%) of the 403 respondents indicated a desire to
      know their HIV status. Most (88.1%) respondents considered locations outside of
      the health facility as preferred places for VCT. The majority (98.7%) of
      respondents approved the use of lay counsellors. About a quarter (24%) of
      respondents believed that it was possible to acquire HIV through sharing a
      drinking cup with a PLWHA. About half (52.1%) of the respondents considered that
      a teacher with HIV/AIDS should not be allowed to teach, while 77.2% would not buy
      vegetables from a PLWHA. Respondents who believed that sharing a drinking cup
      with a PLWHA could transmit HIV infection (OR 2.50, 95%CI 1.52-4.11) and
      respondents without formal education (OR 2.94, 95%CI 1.38-6.27) were more likely
      to stigmatize PLWHAs. In contrast, respondents with knowledge of the availability
      of antiretroviral (ARV) drugs were less likely to do so (OR 0.40, 95%CI 0.22
      0.73). Findings from the thirteen focus group discussions reinforced approval for
      community-based VCT and lay counsellors but revealed concerns about stigma and
      confidentiality. In conclusion, community-based VCT and the use of lay
      counsellors may be acceptable options for promoting access. Interventional
      studies are required to assess feasibility and cost-effectiveness.

PMID- 17207293
TI  - Socioeconomic status during childhood and health status in adulthood: the Wroclaw
      growth study.
AB  - It has been widely observed that socioeconomic status (SES) is associated with
      frequency of cardiovascular disease. Both men and women of low socioeconomic
      position have increased risk of cardiovascular disease morbidity and premature
      death. In this study the relationship between SES in childhood, and health status
      at the age of 50 years was examined. Socioeconomic status in childhood was
      measured using objective (father's educational level and number of children in
      the family) and subjective (self-assessed SES in childhood declared in early
      adulthood) indicators. Data from the Wroclaw Growth Study were completed when
      subjects were 50 years old, and information concerning health status was added.
      The results indicated that the objective, universally used measures of SES in
      childhood such as father's educational level and size of family did not show any
      essential relationships with health outcomes in adulthood, both for men and
      women. By contrast, retrospective, self-assessed SES (as better, average or worse
      as compared with peers) in childhood was significantly associated with the
      appearance of cardiovascular disease among women aged 50 years. Women who at the
      beginning of their adult life declared better socioeconomic condition in
      childhood were significantly healthier at the age of 50 years (OR=3.43; p=0.02).
      Moreover, this appeared to be independent of BMI, SES and life-style in
      adulthood. For men, retrospective self-assessed SES showed no relation to health
      status at the age of 50 years. The gender differences in the relationships
      between self-assessed SES in childhood and health status in adulthood are
      explained by possible selective premature mortality among men from lower
      childhood SES and/or sex differences in cognitive abilities.

PMID- 17207294
TI  - Anticlotting drugs and regional anaesthetic and analgesic techniques: comparative
      update of the safety recommendations.
AB  - The wide use of anticlotting drugs by patients scheduled for surgery is a
      challenge for the anaesthesiologist when considering a regional anaesthesia
      technique. This practice seems safe if there is an appropriate management based
      on safety intervals established according to the pharmacology of the drug and the
      regional technique. Some anaesthesiology societies have published recommendations
      for the safe practice of regional anaesthesia with the simultaneous use of
      anticoagulants (heparin, low molecular weight heparins, oral anticoagulants (OA),
      fondaparinux and others) and antiplatelet agents (aspirin, clopidogrel,
      ticlopidine, argatroban and others). One of the most recent guidelines has been
      published by the Spanish Society of Anaesthesia and Critical Care. This article
      reviews these recommendations and compares them with others published in the last
      years. The recommendations are similar, but some interesting differences can be
      observed and need to be considered. A European consensus in this setting would
      probably be necessary.

PMID- 17207295
TI  - Bivona Hyperflex tracheostomy tube occlusion causing spurious tachypnoea and
      tracheal ulceration.

PMID- 17207296
TI  - Is administration time of oral non-steroid anti-inflammatory drugs important? A
      clinical study in patients undergoing arthroscopic subacromial decompression.

PMID- 17207297
TI  - The transarterial brachial plexus block for hand and forearm surgery: a review of
      1062 cases.

PMID- 17207298
TI  - Perception of training needs and opportunities in advanced airway skills: a
      survey of British and Irish trainees.
AB  - BACKGROUND AND OBJECTIVE: We surveyed delegates at the Group of Anaesthetists in
      Training (UK) meeting to investigate evidence of a training-gap (number of
      fibreoptic intubations believed to bestow competence vs. number actually
      performed). METHODS: Questionnaires were distributed to and collected from
      delegates in person. Questions covered six areas, including experience of
      fibreoptic intubation and cricothyrotomy, fibreoptic intubation as a specialist
      skill and ethical issues. RESULTS: We received 221 replies (76%). All trainees
      believed competence to be achievable with 10 intubations (interquartile range
      (IQR) 10-20); the median number performed was 2 (IQR 0-4). This was statistically
      significant for the groups' senior house officers, 1st and 2nd year registrars
      and 3rd and 4th year registrars; P < 0.0001. Many final year trainees (12/20,
      60%) also failed to achieve their competency target. Few trainees had seen or
      performed any cricothyrotomies (medians 0, IQRs 0-1 and 0-0). Most (195/208, 94%)
      believed that fibreoptic intubation was a core skill and 199/212 (94%) believed
      that all should be competent by completion of training. Ten percent (n = 208)
      felt it unethical to perform an awake training intubation with full consent and
      10% believed it acceptable without explanation. Most (82.7%) would fibreoptically
      intubate an asleep patient (requiring intubation) without consent. CONCLUSION:
      Trainees reported a gap between their perception of competence and achievement in
      awake fibreoptic intubation. Simple and complex simulations and structured
      training programmes may help. Anaesthetists must address the ethics of clinical
      training in advanced airway management.

PMID- 17207299
TI  - A combination of gabapentin and local anaesthetics attenuates acute and late pain
      after abdominal hysterectomy.
AB  - BACKGROUND AND OBJECTIVE: Gabapentin and local anaesthetics may decrease
      postoperative pain and analgesic needs. The aim of the study was to investigate
      the effect of the combination of these drugs on the analgesic needs as well as on
      acute and late pain after abdominal hysterectomy. METHODS: Sixty patients
      undergoing abdominal hysterectomy were randomly assigned to receive
      postoperatively oral gabapentin 400 mg 6 hourly for 7 days plus continuous wound
      infusion of ropivacaine 0.75% for 30 h or placebo capsules identical to those of
      gabapentin for 7 days and continuous wound infusion of normal saline for 30 h.
      Morphine consumption (PCA) for 48 h, paracetamol 500 mg plus codeine 30 mg
      (Lonalgal tablets) intake on days 3-7, visual analogue pain scores at rest and
      after cough during the first 7 postoperative days, the need for analgesics at
      home and the presence and incidence of pain after 1 month were recorded. RESULTS:
      The treatment group consumed less cumulative morphine over the first 48 h (31 +/-
      13.2 mg vs. 50 +/- 20.5 mg in controls, P < 0.001) and less Lonalgal tablets on
      days 3-7 (z = 2.54, P = 0.011). The visual analogue score values at rest and
      after cough did not differ between the groups during the first 7 postoperative
      days. One month postoperatively, fewer patients in the treatment group
      experienced pain due to surgery than in the control group (17/27 vs. 21/24, P =
      0.045). CONCLUSION: Gabapentin and continuous wound infusion with ropivacaine
      0.75% decreased analgesic needs and late pain in patients undergoing abdominal
      hysterectomy.

PMID- 17207301
TI  - PercuTwist: a new alternative to Griggs and Ciaglia's techniques.
AB  - BACKGROUND AND OBJECTIVE: Tracheostomy is one of the most common procedures in
      intensive care units worldwide. In this study we aimed to compare three different
      tracheostomy techniques with respect to duration of procedure and complications.
      METHODS: One hundred and thirty patients requiring endotracheal intubation for
      more than 10 days due to acute respiratory distress syndrome, infections or
      cerebrovascular events were consecutively selected to undergo the percutaneous
      dilatational tracheostomy technique (PDT n = 44), the guide-wire dilating forceps
      technique group (GWDF n = 41) or the PercuTwist technique (n = 45). The time
      taken to perform the procedure (skin incision to successful placement of
      tracheostomy tube) and complications were recorded. RESULTS: The operating times
      were found to be 9.9 +/- 1.1, 6.2 +/-1.4 and 5.4 +/- 1.2 min in PDT, GWDF and
      PercuTwist groups, respectively. The duration of the procedure was significantly
      shorter in the PercuTwist group as compared to the percutaneous dilatational
      tracheostomy (P < 0.01) and guide-wire dilating forceps (P < 0.05) groups. During
      postoperative bronchoscopy, eight cases of longitudinal tracheal abrasion (four
      in the PDT group, two in the GWDF group and two in the PercuTwist group), two
      cases of posterior tracheal wall injury (one in PDT and one in GWDF) and one case
      of tracheal ring rupture in the PDT group were seen. CONCLUSIONS: Percutaneous
      tracheostomy techniques have their own advantages and complications. PercuTwist,
      a new controlled rotating dilatation method, was associated with minimal
      complications, appears to be easy to perform and a practical alternative to
      percutaneous dilatational tracheostomy and guide-wire dilating forceps
      techniques.

PMID- 17207302
TI  - Hypoglossal nerve injury following the use of the CobraPLA.

PMID- 17207303
TI  - The efficacy of rofecoxib 50 mg and hydrocodone/acetaminophen 7.5/750 mg in
      patients with post-arthroscopic pain.
AB  - OBJECTIVE: To compare the efficacy and tolerability of rofecoxib,
      hydrocodone/acetaminophen 7.5 mg/750 mg (H/A) and placebo in treating pain after
      arthroscopy of the knee. METHODS: A randomized, double-blind, placebo-controlled,
      single dose study enrolling patients experiencing moderate or severe pain after
      knee arthroscopy. Patients with moderate-to-severe postoperative pain received
      either rofecoxib 50 mg (n = 151), H/A (n = 145), or placebo (n = 147). Pain was
      measured over 24 h. The primary endpoint was total pain relief at 6 h for
      rofecoxib 50 mg compared with placebo. RESULTS: H/A (p = 0.003), but not
      rofecoxib (p = 0.256) was significantly more effective than placebo for total
      pain relief at 6 h (TOPAR6). Although analgesic onset and peak were significantly
      better for H/A than for both rofecoxib (p < 0.01, p < 0.05, respectively) and
      placebo (p < 0.05, p < 0.001, respectively), rofecoxib patients used
      significantly less rescue analgesia (p < 0.001) over 24 h. Rofecoxib also
      provided better Brief Pain Inventory Severity (p = 0.008) and Interference Domain
      (p = 0.045) scores at 24 h compared to placebo and had lower 24-h Pain Severity
      scores than H/A (p < 0.05). Treatments were generally well tolerated, with no
      significant difference in the frequency of patient-reported adverse events
      between groups. CONCLUSIONS: Rofecoxib 50 mg did not provide significantly
      different pain relief than placebo at 6 h, and the primary endpoint TOPAR was not
      attained, although it did show several efficacy benefits at 24 h, including a
      significant opioid-sparing effect. All treatments were well tolerated, with no
      significant differences observed. The limited efficacy of rofecoxib in this study
      contrasts to the results of previous surgical studies evaluating rofecoxib, and
      may be partially explained by the postoperative dosing in this arthroscopic
      surgical model.

PMID- 17207304
TI  - Fentanyl buccal tablet (FBT) for relief of breakthrough pain in opioid-treated
      patients with chronic low back pain: a randomized, placebo-controlled study.
AB  - BACKGROUND: Short-acting opioids are commonly used to treat breakthrough pain
      (BTP) and rapid-onset formulations are being developed to improve the
      effectiveness of this approach. Fentanyl buccal tablet (FBT) is a new formulation
      of fentanyl that enhances transbuccal drug delivery via an effervescent reaction
      and may provide relatively rapid-onset analgesia. FBT was evaluated for BTP in
      opioid-treated patients with chronic low back pain--the first such study in a
      population with chronic non-cancer pain. DESIGN: Randomized, double-blind,
      placebo-controlled. PATIENTS AND SETTING: Patients with chronic low back pain
      receiving long-term opioid therapy at 16 pain treatment centers in the United
      States. PROCEDURES: Following open-label titration to identify an effective FBT
      dose, patients were randomly assigned to one of three double-blind dose sequences
      (six doses of FBT, three placebo) to treat nine BTP episodes. Pain intensity
      (PI), measured on an 11-point scale (0 = no pain; 10 = worst pain), and other
      outcomes were assessed for 2 h after dosing. DATA ANALYSIS: The primary efficacy
      measure was the sum of pain intensity differences (PIDs) for the first 60 min
      (SPID60); secondary efficacy measures included PIDs at other time points, pain
      relief (PR), meaningful PR, time to meaningful PR, use of supplementary BTP
      medication, and self/investigator-reported adverse events. RESULTS: Of the 124
      patients screened, 105 patients were enrolled, 84 identified an effective FBT
      dose, and 77 entered the double-blind phase. SPID60 significantly favored FBT (p
      < 0.0001). All secondary measures also favored FBT, with PIDs and PR showing
      significant differences versus placebo as early as 10 and 15 min, respectively.
      An improvement in PI score of > or = 33% occurred in a significantly larger
      proportion of FBT-treated episodes versus placebo from 15 min (20% vs. 11%, p <
      0.01) through 2 h (65% vs. 28%, p < 0.0001). Patients were approximately four
      times more likely to require supplemental opioids for BTP episodes following
      administration of placebo compared with episodes treated with FBT. AEs were
      typical for opioids, and were mostly reported during dose titration. Limitations
      of this study may be related to its open-label dose-titration phase (which has
      the potential to compromise blinding) and the recruitment of patients from pain
      clinics, which could potentially yield a study population that is not
      representative of the general population with BTP. CONCLUSIONS: FBT was
      efficacious and well tolerated in the treatment of BTP in opioid-treated patients
      with chronic low back pain.

PMID- 17207305
TI  - Timing of drotrecogin alfa (activated) initiation in treatment of severe sepsis:
      a database cohort study of hospital mortality, length of stay, and costs.
AB  - INTRODUCTION: For patients with critical conditions including severe sepsis,
      minimizing the time from presentation to treatment is important to improving
      outcomes. Understanding the factors influencing high hospital mortality and
      resource utilization in severe sepsis continues to interest clinicians and
      researchers. This study examined the associations between timing of drotrecogin
      alfa (activated) (DrotAA) initiation and hospital mortality, length-of-stay, and
      costs. METHODS: We conducted a cohort study of adult patients (N = 1179) with
      intensive care unit stays from November 2001 to June 2003 who received DrotAA in
      US hospitals with data in the Solucient ACTracker database. We defined evident
      severe sepsis (ESS) as concurrent antibiotic plus ventilator and/or vasopressor
      use. We characterized the interval between ESS and DrotAA initiation as Same-day,
      Next-day, or Day 2+. We compared group characteristics and created multivariate
      models of hospital mortality, length-of-stay, and costs. RESULTS: Forty-three
      percent of patients received Same-day DrotAA, 30% Next-day, and 27% Day 2+. Same
      day and Next-day patients had more organ dysfunctions at ICU admission than Day
      2+ patients (1.1 +/- 0.9 and 1.2 +/- 0.8 vs. 1.0 +/- 0.8; p = 0.021 and p <
      0.001, respectively), but from ESS to DrotAA initiation, organ dysfunctions for
      Day 2+ patients had increased more (+0.0 and +0.4 vs. +0.6, respectively; all p <
      0.0001). Increased mortality was observed with administration later than Same
      day, although only for the Day 2+ group did the association remain significant (p
      < 0.05) after adjusting for clinical and demographic factors. Only Next-day
      initiation was associated with significantly decreased costs (p = 0.0145).
      CONCLUSIONS: Timing of DrotAA initiation is associated with clinical and economic
      outcomes in severe sepsis. The potential impact of this timing on hospital
      mortality, length-of-stay, and costs deserves further study.

PMID- 17207306
TI  - Oxidative stress involvement and gene expression in indomethacin-induced
      gastropathy.
AB  - It has been proposed that neutrophil- and oxygen radical-dependent microvascular
      injuries are important prime events that lead to gastric mucosal injury induced
      by indomethacin. Reactive oxygen species (ROS) produced by activated neutrophils
      after indomethacin treatment cause gastric mucosal injury via ROS-mediated
      oxidation of important biomolecules such as lipid, protein, and DNA. In addition,
      it has been revealed that indomethacin-induced gastric mucosal injury occurs via
      gastric epithelial cell apoptosis. However, there is little known about the
      mechanism of indomethacin-triggered cellular response and apoptotic signaling in
      gastric mucosal cells. In the present study, we summarize the evidence that
      supports the involvement of oxidative stress and apoptosis in indomethacin
      induced gastropathy, and review the gene expression profiles of gastric
      epithelial cells after indomethacin treatment determined by DNA microarray
      analysis.

PMID- 17207307
TI  - Oxysterols in biological systems: sources, metabolism and pathophysiological
      relevance.
AB  - Oxysterols are the 27-carbon products of cholesterol oxidation by both enzymic
      and non-enzymic mechanisms. Their roles in cholesterol homeostasis, as well as in
      diseases in which oxidative damage and lipid peroxidation are implicated (e.g.
      atherosclerosis), have been investigated extensively. However, there are a number
      of important considerations regarding the physiological/pathophysiological
      functions and activities of the different oxysterols. First, in both normal and
      diseased tissues, the levels of oxysterols are very low when compared to the
      native sterol. Also, when assessing studies that have measured the levels of
      oxysterols in biological samples, there must be careful consideration as to the
      method of sample isolation, storage and sampling. This is because of the
      potential generation or loss of oxysterols during these procedures. Additionally,
      the relevance of in vitro studies which examine the effects of oxysterols upon
      cell function should be judged as to cellular oxysterol content (both in terms of
      the levels of oxysterol and the degree of esterification) resulting from the
      oxysterol treatment. We present evidence that the means by which oxysterol is
      delivered in vitro determines whether the oxysterol content reflects what has
      been found in vivo. Studies identifying the specific cellular targets of
      oxysterol indicate that several oxysterols may be regulators of cellular lipid
      metabolism via control of gene transcription.

PMID- 17207308
TI  - The influence of ferrylhemoglobin and methemoglobin on the human erythrocyte
      membrane.
AB  - The aim of the study was to examine and compare the effects of methemoglobin
      (metHb) and ferrylhemoglobin (ferrylHb) on the erythrocyte membrane. Kinetic
      studies of the decay of ferrylhemoglobin (*HbFe(IV)=O denotes ferryl derivative
      of hemoglobin present 5 min after initiation of the reaction of metHb with
      H(2)O(2); ferrylHb) showed that autoredecay of this derivative is slower than its
      decay in the presence of whole erythrocytes and erythrocyte membranes. It
      provides evidence for interactions between ferrylHb and the erythrocyte membrane.
      Both hemoglobin derivatives induced small changes in the structure and function
      of the erythrocyte membrane which were more pronounced for ferrylHb. The amount
      of ferrylHb bound to erythrocyte membranes increased with incubation time and,
      after 2 h, was twice that of membrane-bound metHb. The incubation of erythrocytes
      with metHb or ferrylHb did not influence osmotic fragility and did not initiate
      peroxidation of membrane lipids in whole erythrocytes as well as in isolated
      erythrocyte membranes. Membrane acetylcholinesterase activity increased by about
      10% after treatment of whole erythrocytes with both metHb and ferrylHb. ESR
      spectra of membrane-bound maleimide spin label demonstrated minor changes in the
      conformation of label-binding proteins in ferrylHb-treated erythrocyte membranes.
      The fluidity of the membrane surface layer decreased slightly after incubation of
      erythrocytes and isolated erythrocyte membranes with ferrylHb and metHb. In whole
      erythrocytes, these changes were not stable and disappeared during longer
      incubation.

PMID- 17207309
TI  - In vitro antioxidant activity of Juglans regia L. bark extract and its protective
      effect on cyclophosphamide-induced urotoxicity in mice.
AB  - Walnut (Juglans regia L.) bark has been claimed to possess anti-inflammatory,
      blood purifying, anticancer, depurative, diuretic and laxative activities. It
      contains several therapeutically active constituents, especially polyphenols. We
      studied the antioxidant potential of aqueous extract of walnut bark and its
      modulatory effect on cyclophosphamide (CP)-induced urotoxicity in Swiss albino
      male mice. Free radical-scavenging activity of extract was assessed in four in
      vitro assays. The phenolic and flavonolic contents of the extract were also
      measured. Walnut bark extract treatment (150 mg/kg p.o. x 10 days) resulted in
      protective restoration of decreased antioxidants in CP-treated (18 mg/kg i.p. x
      10 days) animals. CP treatment caused decreases in the activities of catalase
      (CAT), glutathione peroxidase (GP), glutathione reductase (GR) and glutathione S
      transferase (GST) and in the glutathione (GSH) content in urinary bladder and a
      significant concomitant increase in lipid peroxidation (LPO). Administration of
      extract restored all the antioxidants significantly and lowered the elevated LPO
      in the bladder. A correlation between radical scavenging capacities of the
      extract with phenolic content was observed thus justifying its antioxidant
      potential against oxidative stress-mediated urotoxicity in mice. Walnut is
      reported to possess antiproliferative activity. Its protective effect on CP
      induced toxicity in bladder is a promising activity, which warrants possible
      clinical investigations on this medicinal plant.

PMID- 17207310
TI  - Reactive oxygen species, hydrogen peroxide, catalase and diabetes mellitus.

PMID- 17207311
TI  - Clinical trials using chemopreventive vitamin D analogs in breast cancer.
AB  - This article comprehensively reviews the clinical trials and considers the future
      directions of the use of vitamin D and its analogs in the treatment or
      chemoprevention of breast cancer. Chemopreventive treatment strategies strive to
      delay the onset of certain cancers, prevent the progression of malignant disease
      after diagnosis, or delay the advent of recurrence after curative treatment. We
      first summarize the epidemiological evidence that led to the hypothesis that
      vitamin D may have an anti-cancer activity. Vitamin D shows great potential as a
      therapy for breast cancer; however, its use in clinical trials has been hindered
      by the induction of hypercalcemia at a concentration required to suppress cancer
      cell proliferation. This has led to the development of less calcemic analogs of
      vitamin D. We review the clinical trials with breast cancer patients using
      vitamin D analogs.

PMID- 17207312
TI  - Tumor hypoxia and prognosis in human gliomas.

PMID- 17207313
TI  - Integrative oncology: tapping into a research goldmine.

PMID- 17207314
TI  - Considerations on the use of the internet as a tool for minority recruitment into
      clinical trials.

PMID- 17207315
TI  - The interactions of polarographic measurements of oxygen tension and histological
      grade in human glioma.
AB  - PURPOSE: The purpose of this study is to investigate the implications of hypoxia
      and histological grade for survival in patients with gliomas. MATERIALS AND
      METHODS: Tissue oxygen tension was measured intraoperatively using an Eppendorf
      pO2 Histograph. Survival was calculated from the date of the Eppendorf study to
      the date of last follow-up. Univariate analysis was performed stratifying
      patients by patient gender, type of anesthesia used, histological grade, extent
      of surgery, and patient age. Lastly univariate analysis was performed on the
      cohort after dichotomizing the median pO2 at 2.0 mmHg, 5.1 mmHg, and 10.0 mmHg.
      RESULTS: From March of 1996 to June of 1999, 25 patients were entered into this
      prospective trial. Two patients were excluded from analysis because polarographic
      measurements included normal brain tissue as well as tumor. Thus for analysis we
      included 13 patients with high grade gliomas (HGG) and 10 with low grade gliomas
      (LGG). The median tumor oxygen pressure for the entire cohort was 5.1 mmHg.
      Higher grade (P=0.0012) was prognostic for poorer survival. Patients were then
      stratified into groups with a median tumor oxygen tensions either above or below
      2.0 mmHg, 5.1 mmHg, and 10.0 mmHg; there was no significant difference found in
      overall survival. CONCLUSIONS: Although histological grade was prognostic for
      survival, hypoxia, represented as the median tumor oxygen tension, was not a
      significant independent prognostic indicator of survival in this small and
      heterogeneous series of patients.

PMID- 17207316
TI  - Patient initiation of complementary and alternative medical therapies (CAM)
      following cancer diagnosis.
AB  - PURPOSE: Complementary and alternative medicine use is prevalent in both healthy
      and oncologic populations. However, few data exist to quantify complementary and
      alternative medicine initiation specifically after cancer diagnosis. This study
      evaluated patients' complementary and alternative medicine usage patterns,
      reasons, and general perceptions after cancer diagnosis and during or after
      conventional cancer therapy. METHODS: An Internet- and clinic-based piloted
      questionnaire was distributed from July 2004 through September 2004. In total,
      604 responses were analyzed (64% Internet, 36% oncology clinics). Patients were
      predominantly white females; almost half held college or graduate degrees.
      Respondents reported past or present history of >or=1 conventional treatment(s),
      primarily chemotherapy and radiotherapy. RESULTS: Initiation of >or=1
      complementary and alternative medicine after diagnosis was reported by 54% of
      those surveyed. Complementary and alternative medicine users were more likely
      than non-users to have a history of chemotherapy (P=0.003) and enrollment in
      clinical trials (P=0.007). Complementary and alternative medicine use was greater
      in females (P=0.004) and patients with higher education levels (P<0.001), but not
      in whites compared to non-whites (P=0.34). The most commonly cited reason for
      complementary and alternative medicine use after diagnosis was "general overall
      health." Less than one-third of patients cited their healthcare providers as
      primary sources of complementary and alternative medicine information. The vast
      majority of users (86%) expressed satisfaction with complementary and alternative
      medicine as a cost-effective approach. DISCUSSION: About one-half of adult cancer
      patients initiate complementary and alternative medicine therapy after diagnosis
      and during or after conventional oncologic treatments. Healthcare providers
      should be aware of patients' reasons for complementary and alternative medicine
      use, both for symptom management and quality-of-life. Healthcare providers should
      also be familiar with patients' complementary and alternative medicine
      information sources and should supplement these sources with discussions of
      pertinent safety profiles and potential interactions with standard therapies.

PMID- 17207317
TI  - Clinical trial resources on the internet must be designed to reach
      underrepresented minorities.
AB  - PURPOSE: Internet-based clinical trial information services are being developed
      to increase recruitment to studies. However, there are limited data that evaluate
      their ability to reach elderly and underrepresented minority populations. This
      study was designed to evaluate the ability of an established clinical trials
      registry to reach these populations based on expected Internet use. PATIENTS AND
      METHODS: This study compares general Internet users to participants who enrolled
      in an Internet based colorectal cancer clinical trials registry established by
      OncoLink (www.oncolink.org) and the National Colorectal Cancer Research Alliance.
      Observed rates of demographic groupings were compared to those established for
      general Internet users. RESULTS: Two thousand, four hundred and thirty-seven
      participants from the continental United States used the Internet to register for
      the database. New England, the Mid-Atlantic region, and the Southeast had the
      highest relative frequency of participation in the database, whereas the Upper
      Midwest, California, and the South had the lowest rates. Compared to general
      Internet users, there was an overrepresentation of women (73% vs. 50%) and
      participants over 55 years old (27% vs. 14%). However, there was an
      underrepresentation of minorities (10.3% vs. 22%), particularly African Americans
      (3.1% vs. 8%) and Hispanics (2.8% vs. 9%). DISCUSSION: The Internet is a growing
      medium for registry into clinical trials databases. However, even taking into
      account the selection bias of Internet accessibility, there are still widely
      disparate demographics between general Internet users and those registering for
      clinical trials, particularly the underrepresentation of minorities. Internet
      based educational and recruitment services for clinical trials must be designed
      to reach these underrepresented minorities to avoid selection biases in future
      clinical trials.

PMID- 17207318
TI  - 5-fluorouracil mediates apoptosis and G1/S arrest in laryngeal squamous cell
      carcinoma via a p53-independent pathway.
AB  - PURPOSE: 5-Fluorouracil (5-FU) is a commonly used chemotherapeutic agent in the
      treatment of laryngeal squamous cell carcinoma. 5-FU can induce cell cycle arrest
      or apoptosis in various cancers via either a p53-dependent or a p53-independent
      pathway; however, its pathway of action in laryngeal carcinoma is unknown. In
      this study, we aim to investigate the role that p53 plays in the cytotoxic effect
      of 5-FU on laryngeal squamous carcinoma cells. MATERIALS AND METHODS: We employed
      two human laryngeal squamous carcinoma cell lines with different p53 statuses-one
      (UMSCC12) had truncated non-functional p53 and the other (UMSCC11A) had mutant
      but functional p53. Cell death was detected using cytotoxicity assay and Annexin
      V staining. Cell cycles were analyzed by flow cytometry. Western blot was used to
      analyze the protein expression. RESULTS: 5-FU induces apoptosis in both UMSCC12
      and UMSCC11A cells in a dose- and time-dependent manner, suggesting that the
      pathway was p53-independent. 5-FU induced the accumulation of retinoblastoma
      protein and a cyclin dependent kinase inhibitor, p21WAF1/CIP1, in both UMSCC12
      and UMSCC11A cells. However, 5-FU did not induce p53 expression in either UMSCC12
      or UMSCC11A cells. In addition, G1/S cell cycle phase arrest was associated with
      antiproliferative activity of 5-FU in both cell lines. In order to gain an
      insight into the role p53 plays in response to 5-FU treatment in laryngeal
      carcinoma, we further transfected either a wildtype p53 plasmid or an empty
      pcDNA3.1 vector into UMSCC12 cells. We found that 5-FU increased pRb and
      p21WAF1/CIP1 expression in both p53-transfected and vector-transfected cells
      without the significant accumulation of p53. DISCUSSION: Our results suggest that
      5-FU mediates apoptosis and G1/S cell cycle phase arrest in laryngeal carcinoma
      via a p53-independent but p21WAF1/CIP1-dependent or p21WAF1/CIP1-Rb-dependent
      pathway. While p53 does not seem to be involved in 5-FU induced apoptosis and
      cell cycle arrest in laryngeal carcinoma, further studies are needed to examine
      the roles of retinoblastoma protein and p21WAF1/CIP1 in laryngeal carcinoma
      receiving chemotherapy.

PMID- 17207319
TI  - Assessment of salivary function change in nasopharyngeal carcinoma treated by
      parotid-sparing radiotherapy.
AB  - PURPOSE: The purpose of this study was to evaluate function of major salivary
      glands, subjective xerostomia, and correlation between subjective and objective
      xerostomia scoring after precision-oriented radiotherapy for nasopharyngeal
      carcinoma. MATERIALS AND METHODS: From 2000 to 2002, 34 patients with
      histologically proven non-metastatic nasopharyngeal carcinoma received definitive
      therapy by parotid-sparing radiotherapy, which included intensity-modulated
      radiotherapy (33 patients>60 Gy), 3D-conformal radiotherapy, and brachytherapy
      boost. Salivary function was assessed by sialoscintigraphy pre-irradiation and
      post-irradiation at 1, 6, 12, and 18 months. The salivary stimulated secretion
      ratio (SSR) was used to evaluate function of submandibular and parotid glands.
      Subjective and objective xerostomia was monitored by the LENT/SOMA system.
      RESULTS: The median dose to parotid gland was 34.6 Gy (interquartile range, 32.9
      36.5 Gy). The median dose to submandibular gland was 60.5 Gy (interquartile
      range, 58.1-61.5 Gy). Parotid-gland post-irradiation median SSR at 1 (0.01,
      P=0.000) and 6 (0.08, P=0.002) months showed significant reduction compared with
      pre-irradiation data (0.30). After 12 months, parotid-gland median SSR (12
      months, 0.22, P = 0.734; 18 months, 0.16, P=0.885) lost significance compared
      with pre-irradiation data. Submandibular-gland post-irradiation median SSR at 1
      (P=0.000), 6 (P=0.000), 12 (P=0.000), and 18 (P=0.000) months all showed
      significant reduction compared with pre-irradiation data. There were significant
      correlations between LENT/SOMA subjective and objective xerostomia scores at 6
      months (r=0.657, P=0.000), 12 months (r=0.480, P=0.013), and 18 months (r=0.591,
      P=0.002). CONCLUSIONS: With parotid-sparing radiotherapy for nasopharyngeal
      carcinoma, gland function can recover significantly 12 months after radiotherapy.
      There were significant rank-order correlations between LENT/SOMA subjective and
      objective (analytic) grading scores at 6 to 18 months' follow-up.

PMID- 17207320
TI  - Clinicopathological and biological features of DNA tetraploid colorectal cancers.
AB  - PURPOSE: Most studies of colorectal cancers focus on a comparison of DNA diploid
      to non-diploid tumors consisting of tetraploid and aneuploid tumors. Tetraploid
      tumors alone have not been well studied. In the present study,
      clinicopathological and biological features of tetraploid colorectal cancers in
      contrast to those of diploid and aneuploid ones were investigated. PATIENTS AND
      METHODS: DNA ploidy in 278 primary colorectal adenocarcinomas was determined by
      flow cytometry. RESULTS: Among 278 cases, 8% of the cases were tetraploidy, 44%
      were aneuploidy, and 48% were diploidy. Compared to diploid tumors, tetraploid
      tumors were more frequent in advanced stage, high index of S-phase fraction and
      apoptosis, higher expression of Cox-2, c-erbB-2 and heat shock protein, but had
      decreased inflammatory infiltration (P<0.05). Compared to aneuploid tumors,
      tetraploid tumors had a high frequency of microsatellite instability, high
      expression of Cox-2 and heat shock protein (P<0.05). Unlike tetraploid tumors,
      aneuploid tumors had increased p53 expression but did not have microsatellite
      instability (P<0.05). Tetraploidy and aneploidy predicted a worse prognosis in
      the subgroups of stages A-C, proximal colon, p53 negative expression and higher S
      phase fraction (P<0.05). CONCLUSIONS: DNA tetraploid tumors seem, to some extent,
      to exhibit distinct characteristics of clinicopathology and biology compared with
      aneuploid or diploid colorectal cancers.

PMID- 17207322
TI  - sHLA-G expression: is it really worth measuring?
AB  - HLA-G is believed to play a pivotal role in the immunoprotection of the
      semiallogenic embryo. Its expression during pre- and early implantation is
      correlated with the cleavage rate of the embryo. Studies in congenic mice have
      revealed that mRNA of both the maternal and paternal haplotypes are present in
      zygotes and in embryos at all stages of development.

PMID- 17207323
TI  - Donating endogenous stem cells to repair heart attacks.

PMID- 17207324
TI  - Does oocyte cryopreservation have a future in Hungary?
AB  - The Committee of Human Reproduction established by the Hungarian Ministry of
      Health is currently working on a proposition that has the intention to ban oocyte
      cryopreservation in Hungary temporarily. According to the notion of the
      committee, oocyte cryopreservation and the utilization of frozen oocytes entail
      enormous risks for future generations. They argue that the safety of the method
      is unproven. Consequently, their standpoint maintains that cryopreservation
      invariably remains a grave risk factor with regards to the genetic material of
      the oocyte by significantly increasing the risk to the offspring. Therefore,the
      Committee is requesting additional animal experiments to clarify the probability
      of permanent lesions to the spindle and alterations to the genetic material.
      According to their point of view, the suspension of the method is further
      justified since the efficiency of the procedure has yet not reached the level
      required for clinical adaptation. With the proposed forthcoming step,this
      commentary takes the opportunity to make critical comments and clarify necessary
      questions.

PMID- 17207325
TI  - Investigating newborns' mental health.

PMID- 17207326
TI  - Recombinant LH supplementation to recombinant FSH during induced ovarian
      stimulation in the GnRH-antagonist protocol: a meta-analysis.
AB  - This study aims to compare the efficacy of recombinant LH (rLH) supplementation
      for ovarian stimulation in gonadotrophin-releasing hormone-antagonist protocol
      for IVF/intracytoplasmic sperm injection cycles. Search strategies included
      online surveys of databases. The fixed effects model was used for odds ratio (OR)
      and effect size (weighted mean difference, WMD). Five trials fulfilled the
      inclusion criteria. When the meta-analysis was carried out, advantages were
      observed for the LH supplementation protocol with respect to higher serum
      oestradiol concentrations on the day of human chorionic gonadotrophin
      administration P < 0.0001; WMD: 514, 95% CI 368, 660) and higher number of mature
      oocytes (P = 0.0098; WMD: 0.88, 95% CI 0.21, 1.54). However, these differences
      were not observed in the total amount of recombinant FSH (rFSH) administered,
      days of stimulation, number of oocyets retrieved, the clinical pregnancy rate per
      oocyte retrieval, the implantation rate and miscarriage rate. This result
      demonstrates that the association of rLH with rFSH may prevent any decrease in
      oestradiol after antagonist administration and that a significantly higher number
      of mature oocytes was available for laboratory work. Nevertheless, it failed to
      show any statistically significant difference in clinically significant end
      points in IVF (implantation and pregnancy rates). Additional randomized
      controlled trials are needed to confirm these results further.

PMID- 17207327
TI  - A comparison between follitropin alpha filled by mass and follitropin alpha
      filled by bioassay in the same egg donors.
AB  - This study assessed the ovarian stimulation characteristics of recombinant
      follitropin alpha filled by mass (rFSH-fbm) versus recombinant follitropin alpha
      filled by conventional bioassay (rFSH-bio) in the same egg donor patients. Eleven
      egg donors, who had two ovarian stimulation cycles for oocyte retrieval (total of
      23 cycles), one with rFSH-bio (Gonal-f Multidose) and the second one with rFSH
      fbm (Gonal-f RFF), were evaluated. The protocol of ovarian stimulation was
      exactly the same in both cycles, consisting of GnRH suppression (luteal phase)
      followed by exclusive stimulation with rFSH. Despite no differences in the number
      of days of rFSH treatment and in the total dosage of rFSH administered, the
      number of follicles >14 mm and the number of oocytes retrieved were significantly
      higher in the rFSH-fbm group (P = 0.01 and 0.04 respectively). The mean
      oestradiol peak values showed a trend in favour of rFSH-fbm (3123 versus 2405
      pg/ml respectively). These results suggest that the consistency in dosing
      provided by follitropin alpha filled by mass as opposed to follitropin alpha
      filled by bioassay offers added value for the ovarian stimulation of oocyte donor
      patients.

PMID- 17207328
TI  - Aphasia: an early uncommon complication of ovarian stimulation without ovarian
      hyperstimulation syndrome.
AB  - Thromboembolic disease associated with assisted reproductive techniques is
      extremely rare. A 21-year-old woman with primary infertility underwent an
      ovulation induction cycle with luteal long protocol. Twenty-four hours following
      oocyte retrieval, the patient complained of difficulty in speaking. On
      neurological examination, mild disorientation, motor aphasia, and right-sided
      hypoesthesia were noted. Brain computed tomography scanning without contrast
      revealed left parietal lob infarct. Brain magnetic resonance imaging (MRI), MRI
      angiography (MRA) and perfusion MRI demonstrated an occlusion of the posterior
      division of the left middle cerebral artery (MCA). Physical, ultrasound
      examinations and laboratory test evaluation failed to reveal ovarian
      hyperstimulation syndrome. Except for ovarian stimulation, no additional risk
      factors for stroke were shown. Following anticoagulation and speech therapy, the
      patient recovered completely within eight months. One year after the left MCA
      thrombosis, she conceived spontaneously and had an uncomplicated vaginal delivery
      of a live male infant weighing 2900 g at 38 weeks gestation. This case supports
      that ovulation induction and assisted reproductive techniques may be a newly
      recognized cause of cerebral infarction in otherwise healthy women.

PMID- 17207329
TI  - Oxytocin--a stimulator of directed sperm transport in humans.
AB  - Rhythmic peristaltic contractions of the muscular wall of the non-pregnant
      uterus, as well as rapid sperm transport from the vagina to the Fallopian tubes,
      have long been documented by means of vaginal sonography and
      hysterosalpingoscintigraphy. Uterine peristaltic activity reaches a maximum
      before ovulation and is controlled via oestradiol secretion from the dominant
      follicle systemically and into the utero-ovarian countercurrent system; it is
      also enhanced by oxytocin. In this study, the effect of oxytocin and its receptor
      antagonist atosiban on uterine peristalsis and thus directed sperm transport
      during the mid and late follicular phases was examined. Atosiban did not show any
      effect either on frequency or on pattern of the peristaltic contractions.
      However, oxytocin significantly increased the rapid and directed transport of
      radiolabelled particles representing spermatozoa from the vagina into the
      Fallopian tube ipsilateral to the site of the dominant follicle (P = 0.02, 0.04
      and 0.02 after 1, 16 and 32 min of documentation respectively). It seems
      reasonable to assume that oxytocin plays an important, although not critical,
      role in the mechanisms governing rapid sperm ascension that, at least in humans,
      were developed to rapidly preserve an aliquot of spermatozoa following
      intercourse.

PMID- 17207330
TI  - Donor oocyte dysmorphisms and their influence on fertilization and embryo
      quality.
AB  - The aim of this study was to identify predictors of fertilization rate (FR) and
      embryo quality (EQ) in 126 donor women who underwent 160 intracytoplasmic sperm
      injection (ICSI) cycles. Main outcome measures were oocyte dysmorphisms (OD)
      [perivitelline space (normal/large), perivitelline debris (no/yes), oocyte shape
      (spherical/non-spherical), zona pellucida (normal/abnormal), first polar body
      morphology (normal/fragmented or irregular), cytoplasmic granularity
      (normal/excessive), cytoplasmic vacuoles (no/yes) and colour of cytoplasm
      (normal/dark)], semen source (ejaculated or testicular), donor age, number of
      days of stimulation, plasma oestradiol concentration (pg/ml) on the day of human
      chorionic gonadotrophin administration, FR and day 2 EQ. No significant
      predictors of fertilization were identified. However, the presence of a dark
      cytoplasm decreased by 83% the likelihood of obtaining good quality embryos
      (OR=0.17; 95% CI: 0.04-0.74). Oocytes with a larger than normal perivitelline
      space were associated with 1.8 times higher chance of having good quality embryos
      (OR=1.80; 95% CI: 1.15-2.80). Patients and ovarian stimulation characteristics
      evaluated here did not affect FR and EQ. ICSI technique may guarantee good FR in
      spite of OD; however, certain cytoplasmic anomalies at the oocyte level, such as
      a dark cytoplasm, could compromise subsequent embryo development.

PMID- 17207331
TI  - Assessment of human oocyte developmental competence by cumulus cell morphology
      and circulating hormone profile.
AB  - The predictive value of the morphology of the cumulus--oocyte complex (COC) has
      not yet been explored as a possible factor contributing to the success of human
      in-vitro maturation (IVM). In the present study, development-supporting
      competency of oocytes encircled in a large ( > or = 5) (grade A), moderate (3
      approximately 4) (grade B) or small ( < or = 2) (grade C) number of cumulus cell
      layers was assessed, together with changes in hormonal profile following a
      truncated course of 150 IU pure FSH administration for 3 days prior to aspiration
      on laparoscopy indicated for endometriosis. FSH priming increased the number of
      COC aspirated without changing the proportion of the three morphological types of
      COC, which were then subjected to IVM in the presence of 200 mIU/ml FSH plus 1000
      mIU/ml human chorionic gonadotrophin, followed by intracytoplasmic sperm
      injection. The highest development-supporting competence was observed not with
      oocytes in grade A COC harvested from natural cycles, but with oocytes in grade B
      COC from FSH-primed cycles. Hormonal profiles in patients bearing grade B COC
      were characterized by moderate response in oestradiol and progesterone production
      following FSH, with LH/FSH ratio being below 1.0. It is concluded that an optimal
      window of hormonal profile(s) may exist for follicle aspiration to obtain grade B
      COC in FSH-stimulated human IVM cycles.

PMID- 17207332
TI  - Oocyte cryopreservation: clinical outcome of slow-cooling protocols differing in
      sucrose concentration.
AB  - Oocyte cryopreservation represents an important option for management of female
      fertility, avoiding the ethical concerns associated with embryo storage. This
      retrospective study evaluated the clinical outcome of two alternative slow
      freezing protocols involving different sucrose concentrations. From January 2004
      to March 2006, spare oocytes from selected couples undergoing IVF or
      intracytoplasmic sperm injection were frozen using a slow-cooling protocol and
      thawed at a later stage. Patients were divided into two groups: group A (n = 65),
      whose oocytes were frozen with propane-1,2-diol (PrOH) and 0.1 mol/l sucrose; and
      group B (n = 66) whose oocytes were frozen with 0.3 mol/l sucrose. A total of 543
      oocytes were thawed in group A and 601 in group B, achieving a survival rate of
      24.3 and 71.2% respectively. Whilst fertilization rate (53.5 and 80.4%
      respectively) was higher in group B, enhanced results for group A were achieved
      over all (implantation rate per transferred embryos 12.2 versus 5.7%; pregnancy
      rate per transfer 16.7 versus 9.5%). Normal births and ongoing pregnancies have
      occurred in both groups. Although in slow-cooling methods higher sucrose
      concentration in the freezing mixture allows higher post-thaw survival and
      fertilization rates, overall this did not coincide with an improved clinical
      outcome.

PMID- 17207333
TI  - Differential sucrose concentration during dehydration (0.2 mol/l) and rehydration
      (0.3 mol/l) increases the implantation rate of frozen human oocytes.
AB  - Novel protocols have increased survival and fertilization rates of cryopreserved
      oocytes. Nevertheless, in most cases clinical experiences have been disappointing
      or contradictory. Human oocytes of 141 patients were cryopreserved using a
      modified slow-cooling protocol involving 1.5 mol/l propane-1,2-diol (PrOH) and
      0.2 mol/l sucrose during dehydration, while rehydration was conducted applying
      decreasing concentrations of PrOH and 0.3 mol/l sucrose. One thousand and eighty
      three oocytes were frozen and 403 were thawed, with a survival rate of 75.9%.
      Among the 306 surviving oocytes, 252 were microinjected and 192 (76.2%) showed
      two pronuclei. One hundred and eighty zygotes (93.8%) cleaved. The proportion of
      good quality embryos (grade I and II) was 86.2%. All embryos were transferred and
      17 clinical pregnancies were obtained. Pregnancy rates were 21.3% per transfer,
      21.8% per patient, and 18.9% per thawing cycle. The implantation rate was 13.5%
      while the miscarriage rate was 11.8%. To date, four babies have been delivered,
      while the remaining pregnancies are ongoing. Increased oocyte survival rates can
      be achieved by moderately high sucrose concentrations in the freezing and thawing
      solutions. This also ensures elevated success rates in terms of fertilization,
      embryo development and clinical outcome.

PMID- 17207335
TI  - Cryotop vitrification of human oocytes results in high survival rate and healthy
      deliveries.
AB  - Vitrification, an ultra-rapid cooling technique, offers a new perspective in
      attempts to develop an optimal cryopreservation procedure for human oocytes and
      embryos. To further evaluate this method for human oocytes, 796 mature oocytes
      (metaphase II) were collected from 120 volunteers. Since Italian legislation
      allows the fertilization of a maximum of only three oocytes per woman, there were
      463 supernumerary oocytes; instead of being discarded, they were vitrified. When,
      in subsequent cycles, these oocytes were utilized, 328 out of 330 (99.4%) oocytes
      survived the warming procedure. The fertilization rate, pregnancy rate and
      implantation rate per embryo were 92.9, 32.5 and 13.2% respectively. Thus, as
      already reported in the literature, the vitrification procedure seems to be
      highly effective, safe (since healthy babies have been born) and easy to apply.
      In situations where embryo cryopreservation is not permitted (as in Italy), there
      is now good indication for routine application of the method, once further
      standardization is achieved.

PMID- 17207337
TI  - Air fluid versus fluid-only models of embryo catheter loading: a systematic
      review and meta-analysis.
AB  - The objective of this systematic review was to determine the beneficial or
      detrimental effect of using air bubbles to bracket the embryo-containing medium
      during embryo transfer. To test this theory, a meta-analysis of randomized trials
      comparing air fluid versus fluid-only methods was performed. The primary outcome
      measures were live birth, ongoing and clinical pregnancy rates. The secondary
      outcome measures were the rates of implantation, miscarriage, multiple and
      ectopic pregnancies and retained embryos. Electronic (e.g.PubMed, EMBASE,
      Cochrane Library) and hand searches of the literature revealed two included
      studies (298 women). Meta-analysis was conducted using the Mantel-Haenszel method
      (fixed-effect model). For the primary outcome measures, there were no significant
      differences between the two methods with regards to live birth (OR = 1.34; 95% CI
      = 0.59-3.07), ongoing pregnancy (OR = 1.34; 95% CI = 0.59-3.07) and clinical
      pregnancy (OR = 1.13; 95% CI = 0.70-1.83) rates. For the secondary outcomes,
      there were no significant differences between the two groups. In conclusion there
      is insufficient evidence to suggest that the fluid-only method is superior to the
      use of air brackets during embryo loading. There is a need for well-designed and
      powered randomized trials to determine any possible benefit to either method.

PMID- 17207338
TI  - Early cleavage: an additional predictor of high implantation rate following
      elective single embryo transfer.
AB  - The value of early cleavage (EC) assessment is still being debated. The aim of
      this prospective study was to examine the predictive value of EC assessment
      performed exactly 26 h after insemination by IVF or intracytoplasmic sperm
      injection (ICSI) in a programme of elective single embryo transfer (SET)
      performed at day 2. If day 2 scoring demonstrated several embryos with high
      implantation potential, an EC embryo was transferred preferentially. EC was
      assessed only during normal laboratory hours so that there were two groups: EC
      assessed, and EC not assessed, the latter being the control. A total of 277
      elective SET were performed in women under 37 years undergoing their first IVF or
      ICSI cycle (mean age 30.5 years, range 21-37). The overall clinical and ongoing
      pregnancy rates were 40.1% (111/277) and 32.9% (91/277) respectively.
      Significantly higher overall clinical and ongoing pregnancy rates were obtained
      after transfer of an EC embryo than a non-EC embryo: 49.4 versus 33.3% (P < 0.05)
      and 42.4 versus 25.9% (P < 0.02) respectively. However there was no significant
      difference between the EC assessed and control groups: 40.4 versus 39.3% and 33.2
      versus 32.1 respectively. These findings confirm the value of EC assessment for
      selection of embryos with high implantation potential.

PMID- 17207339
TI  - High rate of biological loss in assisted reproduction: it is in the seed, not in
      the soil.
AB  - The vast majority of embryos produced in vitro and transferred fail to develop
      into an infant, supporting the concept that only a small fraction of embryos is
      destined to become a live birth. One of the main reasons for such a low embryo-to
      infant ratio is the remarkably high number of embryos that after preimplantation
      genetic diagnosis are found to have a chromosome imbalance. This study reports
      the overall biological wastage from oocytes inseminated to ongoing pregnancies in
      patients undergoing preimplantation genetic screening (PGS) because of advanced
      age, recurrent pregnancy losses or multiple failed IVF cycles. The analysis of
      biological wastage per oocyte showed that in this cohort of patients, of 333 eggs
      inseminated, 183 (55.0%) provided embryos for biopsy, and of these, only 33
      (18.0% per embryo and 9.9% per oocyte) were normal. A total of 26 embryos were
      suitable for transfer (14% per embryo and 7.8% per oocyte), but only five (1.5%)
      implanted and three (1.0%) resulted in live births. In conclusion, there is
      enormous biological wastage during assisted reproduction, and the data obtained
      from both embryos and oocytes of patients undergoing PGS support the concept that
      many embryos and eggs obtained during IVF are intrinsically abnormal and thus
      fail to implant.

PMID- 17207341
TI  - Effect of granulocyte-macrophage colony stimulating factor on growth, resistance
      to freezing and thawing and re-expansion of murine blastocysts.
AB  - Two-cell murine embryos were cultured for 72 h in the presence or absence of
      granulocyte-macrophage colony stimulating factor (GM-CSF), frozen for 60 days
      and, after thawing, cultured for an additional 24 h in the presence or absence of
      GM-CSF. During the initial 72 h period, GM-CSF did not influence the percentage
      of embryos reaching the expanded blastocyst stage, but there was a significant
      increase (P < 0.05) in the number of cells in the embryos grown with GM-CSF.
      Survival after thawing was not affected by previous exposure to GM-CSF, but re
      expansion of the blastocoele was diminished in that group. Exposure to GM-CSF
      during the post-thaw period greatly enhanced re-expansion of the blastocoele. The
      presence of human serum albumin in the culture media is thought to have masked
      the beneficial effect of GM-CSF upon embryos.

PMID- 17207342
TI  - Mechanisms of implantation.
AB  - Successful embryo implantation in mammals requires the co-ordinated development
      of a blastocyst competent to implant and an adhesive endometrium. Given the
      indispensable role of implantation for the furtherance of the species, a number
      of molecular mechanisms have evolved to regulate the process. A variety of
      molecules, produced by embryo as well as maternal tissue participates in the
      cross-talk between the implanting blastocyst and the endometrium. The interplay
      between the various molecules and the routes in which they are involved is
      beginning to be elucidated. Because impaired implantation represents the most
      important limiting factor in the establishment of pregnancy, it is believed that
      research in the field will allow clinicians to improve the respective rates. This
      paper reviews certain groups of molecules that are considered to have key roles
      in the mechanisms of implantation.

PMID- 17207343
TI  - Stem cells from human/cow hybrid embryos?

PMID- 17207344
TI  - Intrauterine insemination in The Netherlands.
AB  - The aim of this retrospective study was to assess the results of intrauterine
      insemination (IUI) in The Netherlands, using data from 2003 taken from hospital
      annual reports and reports from individual gynaecologists. By extrapolation, the
      total number of IUI cycles performed that year nationwide, and the related
      outcomes, was estimated. IUI was performed in 91 of the country's 101 hospitals.
      Of these, 58 (64%) registered their IUI results and performed 19,846 IUI cycles.
      The mean pregnancy rate per cycle was 9.0% and the ongoing pregnancy rate per
      cycle was 7.3%. Multiple pregnancies occurred in 9.5% of the ongoing pregnancies.
      Extrapolation of the data suggested that approximately 28,500 IUI cycles were
      performed, of which approximately 2000 resulted in an ongoing pregnancy. The
      number of multiple pregnancies following IUI was estimated to be 180 (9.0%).
      According to the national IVF registry, 9761 IVF cycles were started in 2003,
      resulting in 2,028 ongoing pregnancies (20.8% per cycle) and 439 twin pregnancies
      (21.6% per ongoing pregnancy). In conclusion, the pregnancy rate per IUI cycle in
      The Netherlands (9.0%) was comparable with that reported in the international
      literature (8.7%). The contribution made by IUI to the number of multiple
      pregnancies in The Netherlands was much smaller than the contribution made by
      IVF.

PMID- 17207346
TI  - Endometrial expression of IL-1RtI in patients undergoing miscarriage or
      unsuccessful IVF cycles.
AB  - This study sought to compare the endometrial expression of interleukin-1 receptor
      type I in patients with a history of spontaneous recurrent miscarriage and
      patients with unsuccessful IVF cycles. Eight patients who had undergone two or
      more consecutive unsuccessful IVF cycles (group I), in which at least one good
      quality embryo was transferred, and 18 patients with at least three spontaneous
      late miscarriages (group II) were included in the study. Endometrial and
      follicular development were evaluated by ultrasonography. Plasma concentrations
      were evaluated for FSH and prolactin on cycle day 3 and for progesterone on day 7
      after ovulation, when an endometrial biopsy was performed; samples were
      cryopreserved for interleukin-1 receptor type I immunohistochemistry and embedded
      in paraffin for endometrial dating. Patients with no ovulation or any anomalies
      in hormone concentrations, uterine cavity or endometrial histology were excluded.
      Interleukin-1 receptor type I was expressed in the lumenal epithelium of both
      groups. There was a significant difference (P = 0.0357, two-tailed Fisher's exact
      test) in the glandular epithelium expression of interleukin-1 receptor type I
      between groups I (87.5% of patients) and II (38.9% of patients). Endometrial
      expression of interleukin-1 receptor type I does not seem to be involved in
      embryo implantation in IVF patients, but may play a role in spontaneous recurrent
      miscarriage.

PMID- 17207347
TI  - Raoul Palmer: a maker of fate.
AB  - The privilege of old age is to possess a synthetic view over the past and to
      appreciate the evolution of decisive and determinative episodes in various
      clinical fields. In my lifetime as a gynaecologist and obstetrician, I have
      witnessed wide changes in contraception, epidural anaesthesia in obstetrics, IVF,
      and so on ... Each time, these revolutions were sustained by men and women of
      exceptional stature. One such revolution concerned the introduction of
      laparoscopy into clinical practice. To this end, I wish to tell the story of one
      of my professors who was a determined pioneer in its development.

PMID- 17207348
TI  - Comparative analysis of quality and consistency of urinary and recombinant FSH-
      comments on a recent article.

PMID- 17207351
TI  - [Understanding of multiple organ dysfunction syndrome a revist].

PMID- 17207352
TI  - [Clinical epidemiology of 1,087 patients with multiple organ dysfunction
      syndrome].
AB  - OBJECTIVE: To investigate the clinical epidemiological characteristics of
      multiple organ dysfunction syndrome (MODS) in China. METHODS: A multiple-center
      and prospective survey of the patients with MODS admitted to 37 hospitals in 11
      provinces from March 2002 to January 2005. RESULTS: The original causes of the
      MODS were still severe infection, major operations, shock, cardio-pulmonary
      resuscitation, trauma, and severe acute pancreatitis. The age of 66.1% patients
      was over 60 years in 1 087 patients. The total mortality of the 1 087 patients
      was 60.4%. With the age increased, the mortality also increased. The mortalities
      of the group with simple dysfunction of the brain, lung, kidney, blood,
      cardiovascular system and gastrointestinal tract were higher than those of the
      group with the normal organ function. The mortality increased obviously with the
      numbers of the dysfunction organs. The methods of supportive treatment for the
      dysfunctional organs were more sophisticated than before. Especially the rates of
      administration of blood purification, parenteral alimentation, and enteral
      alimentation were higher. CONCLUSION: Although the methods of supportive
      treatment in the dysfunctional organs are more sophisticated, the mortality of
      the MODS was still as high as 60.4%. The number of patients with age higher than
      60 years was 713 cases (66.1%), therefore how to manage senile-MODS has become a
      major problem. Cardiovascular system, the brain, kidney, gastrointestinal tract,
      lung, liver and blood were the main organs involved, and the mortality of
      dysfunction of cardiovascular system ranked the highest.

PMID- 17207354
TI  - [Primary investigation of the relationship between glucocorticoid induced leucine
      zipper and inflammatory reaction].
AB  - OBJECTIVE: To investigate the mechanism of the action of glucocorticoid induced
      leucine zipper (GILZ) in inflammatory reaction. METHODS: Human monocyte cell line
      THP-1 cells were divided into two groups and cultured in non-serum RPMI1640
      medium.In one group the cells were treated with dexamethasone (DEX). Twelve hours
      later total RNA and total protein were abstracted in both two groups. The mRNA
      encoding for expression of GILZ was semiquantitatively detected by reserve
      transcriptase-polymerase chain reaction (RT-PCR). Protein expression of nuclear
      factor-KappaB (NF-KappaB) p65 and activator protein-1 (AP-1) were assessed by
      Western blotting. Peripheral blood of 10 trauma patients [injury severity score
      (ISS) >or=16 scores] were collected and the leukocytes were isolated within 24
      hours after trauma. The leukocytes were divided into two groups and cultured in
      non-serum medium. In one group the cells were treated with DEX. Twelve hours
      later total RNA and total protein were abstracted in both two groups. The mRNA
      encoding for expression of GILZ was semiquantitatively detected by RT-PCR.
      Protein expression of NF-KappaB p65 and AP-1 were assessed by Western blotting.
      RESULTS: Stimulated by DEX, the expression of GILZ mRNA was increased both in THP
      1 cells and the leukocytes of trauma patients compared with those of control
      groups (both P<0.01). Whereas, protein expressions of NF-KappaB p65 and AP-1 of
      THP-1 cells and leukocytes in peripheral blood of trauma patients were decreased
      in the stimulation groups compared with those of control groups (all P<0.01).
      CONCLUSION: The expression of GILZ gene is up-regulated by glucocorticoid.
      Overexpression of GILZ inhibits NF-KappaB and AP-1 activities, suggesting that
      GILZ possesses anti-inflammatory function.

PMID- 17207355
TI  - [Role of polymorphonuclear neutrophil apoptosis and expression of Fas and caspase
      3 in the systemic inflammatory response syndrome].
AB  - OBJECTIVE: To study the role of the polymorphonuclear neutrophil (PMN) apoptosis
      and expression of Fas and caspase-3 in the systemic inflammatory response
      syndrome (SIRS). METHODS: Eight acute pancreatitis patients with SIRS, 6 healthy
      control subjects were enrolled to study apoptosis of PMN in peripheral blood
      samples, expression of Fas/Fas ligand (FasL) and caspase-3 in the PMN, the levels
      of serum interleukin-6 (IL-6) and IL-8 were observed. RESULTS: Spontaneous
      apoptosis was significantly delayed in PMN from the SIRS patients with higher
      serum IL-6 and IL-8 levels compared with controls (both P<0.01). PMN apoptosis
      rate in peripheral blood of patients with SIRS was lowered than that of controls
      (P<0.01). The expressions of Fas and caspase-3 in the peripheral circulating PMN
      were higher in the controls than those in the SIRS patients (both P<0.01). Serum
      FasL expression was not found by Western blotting 24 hours after culture of PMN
      in vitro. CONCLUSION: Peripheral circulating PMN from acute pancreatitis patients
      with SIRS show delayed apoptosis, decreased expressions of Fas and caspase-3, and
      prolonged PMN survival may contribute to the development of systemic inflammatory
      injury characteristic of SIRS.

PMID- 17207356
TI  - [Clinical evaluation of execution of early goal directed therapy in septic
      shock].
AB  - OBJECTIVE: To evaluate the efficacy of early goal directed therapy (EGDT) in
      septic shock. METHODS: Two hundred and three patients with septic shock were
      assigned into treatment group (n=98) and control group (n=105). According to the
      state of organ function at the beginning of treatment and multiple organ
      dysfunction syndrome (MODS) evaluation scores, each group was categorized into
      three strata: stratum A (mild organ dysfunction), stratum B (medium organ
      dysfunction) and stratum C (severe organ dysfunction). Mortality and incidence of
      organ dysfunction in each group were analyzed. RESULTS: At stratum A, the
      mortality and incidence of organ dysfunction in treatment group were
      significantly lower than those of control group [27.78% (15/54 cases) vs. 37.50%
      (18/48 cases), 31.48% (17/54 cases) vs. 43.75% (21/48 cases), both P<0.05]. There
      was no significant difference between treatment group and control group in
      patients of stratum B [75.86% (22/29 cases) vs. 76.92% (20/26 cases), 55.17%
      (16/29 cases) vs. 57.69% (15/26 cases)] and stratum C [93.33% (14/15 cases) vs.
      96.77% (30/31 cases), 40.00 % (6/15 cases) vs. 41.93% (13/31 cases), all P>0.05].
      CONCLUSION: In the earlier period of septic shock, EGDT can remarkably decrease
      the patients'mortality and incidence of organ dysfunction, but can not improve
      survival rate and prognosis in patients in advanced stage of septic shock.

PMID- 17207357
TI  - [Association between cluster of differentiation 14 polymorphism and
      susceptibility of infection].
AB  - OBJECTIVE: To investigate the association between the single nucleotide
      polymorphisms (SNPs) of cluster of differentiation 14 (CD14) and susceptibility
      in patients with sepsis. METHODS: One hundred and twelve patients with sepsis
      admitted to the intensive care unit (ICU) from December 2004 to March 2006 were
      enrolled for study. Another 100 healthy volunteer donors were chosen serving as
      the normal control group. Genotypes and alleles of CD14-159 C/T, CD14-260 C/T
      were determined in patients and healthy controls by means of restriction fragment
      length polymorphism (RFLP) analysis of polymerase chain reaction (PCR) products.
      Distributional differences of genotypes and alleles between patients and healthy
      controls were analyzed. The sepsis patients were divided into survivor group and
      non-survivor group depending on survival for 28 days. Distributional differences
      of genotypes and alleles between survivor group and non-survivor group were
      determined. RESULTS: The rates of CD14-159 C/T genotypes and T-alleles in
      patients with sepsis were significantly higher than those of healthy volunteers
      (P=0.005 and P=0.000). There were no significant differences in the rates of CD14
      260 C/T genotypes and T-alleles in two groups (P=0.912 and P=0.706). The rates of
      CD14 -159 C/T genotypes and T-alleles in non-survivors were significantly higher
      than those of survivors (both P=0.000). There were no significant differences in
      the rates of CD14-260 C/T genotypes and T-alleles in two groups (P=0.643 and
      P=0.890). CONCLUSION: The differences of CD14-159 C/T genotypes of SNPs may be
      associated with the higher risk of susceptibility and mortality of sepsis.

PMID- 17207359
TI  - [Value of monitoring oxygen metabolism in multiple organ dysfunction syndrome
      after severe trauma].
AB  - OBJECTIVE: To study changes in oxygen metabolism and evaluate metabolic status in
      tissue and cell after severe trauma, and to investigate value of monitoring
      oxygen metabolism in the course of development of multiple organ dysfunction
      syndrome (MODS) in trauma between patients. METHODS: The data of 146 patients
      with severe trauma in Tongji Hospital were collected. The variables pertaining to
      oxygen metabolism were analyzed, and the data were compared between patients with
      risky trauma and those with severe trauma, between patients complicated with MODS
      and non--MODS (NMODS), and between survivors and nonsurvivors. With patients with
      minor trauma as control, the data were analyzed according to injury severity
      score (ISS), revised trauma score (RTS), acute physiology and chronic health
      evaluation II (APACHE II), trauma and injury severity score (TRISS(RTS)) methods
      for trauma and outcome study of probability of survival (Ps). RESULTS: Oxygen
      metabolism abnormality was found after trauma, and it was correlated with ISS,
      RTS, injured organ or region and number of injured organs, shock, systemic
      inflammatory response syndrome (SIRS) and respiratory complications. It was more
      intense in the patients with MODS. There was marked difference in the ratio of
      change in oxygen metabolism between MODS and NMODS groups. Oxygen deficiency
      metabolic variables tended to deteriorate in the non survival group. More marked
      changes in metabolic variables indicated severer organ dysfunction, reaching
      their peak values before death. CONCLUSION: Changes in level of oxygen metabolism
      might be closely correlated with development of MODS in trauma patients. Dynamic
      monitorings of metabolic status of tissue and cell are valuable in predicting the
      development of MODS after severe trauma.

PMID- 17207360
TI  - [Apoptosis of circulating lymphocyte in surgical critically ill patients
      associated with poor outcome].
AB  - OBJECTIVE: To investigate the role and mechanism of lymphocyte apoptosis in post
      operative critically ill patients and to determine the effects of lymphocyte
      apoptosis on the outcome of post-operative critically ill patients. METHODS:
      Thirty-nine consecutive post-operative patients admitted to the intensive care
      unit (ICU) were included in the prospective study. In addition, 30 healthy blood
      donors were involved for comparison. Early signs of apoptosis were investigated
      using flow cytometric measurement of Annexin-V binding to the cell surface of
      peripheral lymphocytes. In patients, absolute lymphocyte counts were measured on
      day 1, 3 and 5. The correlations of secondary infection and ICU stay duration
      with lymphocyte apoptosis and lymphocyte counts were determined. RESULTS: Post
      operative critically ill patients exhibited higher rate of lymphocyte apoptosis
      than controls [(10.82+/-3.32)% vs. (2.89+/-1.17)%, P<0.01]. Meanwhile, lymphocyte
      counts were decreased significantly in patients compared with healthy individuals
      [(1.41+/-1.26) x 10(9)/L vs. (2.58+/-0.62) x 10(9)/L, P<0.01]. In patients group,
      rate of lymphocyte apoptosis was significantly higher in patients with secondary
      infection compared with those without secondary infection [(12.67+/-3.11)% vs.
      (9.24+/-2.63)%, P<0.01], and lymphocyte counts had no difference on day 1, while
      on day 3 and day 5 were decreased significantly in patients with secondary
      infection compared with those without secondary infection [(0.68+/-0.35) x
      10(9)/L vs. (1.30+/-1.33) x 10(9)/L, (0.72+/-0.40) x 10(9)/L vs. (1.34+/-1.11) x
      10(9)/L, respectively, stay duration of post-operative patients was positively
      correlated with rate of lymphocyte apoptosis (r=0.412, P=0.009) and negatively
      correlated with day 1, 3 and 5 lymphocyte counts, significantly correlated with
      day 1 and day 5 (r(1)=-0.333, r(5)=-0.361, both P<0.05). CONCLUSION: Lymphocyte
      apoptosis is enhanced in peripheral blood of post-operative critically ill
      patients and leads to a profound and persistent lymphopenia associated with poor
      outcome such as secondary infection and delay of ICU stay duration. Further
      studies are required to examine whether intervention to prevent lymphocyte
      apoptosis might alter the patients' outcome.

PMID- 17207361
TI  - [Alteration in serum cytokines of patients with multiple organ dysfunction
      syndrome after liver transplantation].
AB  - OBJECTIVE: To explore the serum cytokine fluctuation in those adult patients with
      multiple organ dysfunction syndrome (MODS) during the post-operation stage of
      orthotopic liver transplantation (OLT) to guide the clinical treatment. METHODS:
      Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL
      8 and IL-10 were determined in 53 MODS patients who had received OLT. They were
      divided into two groups as control group and experimental group, according to
      whether continuous blood purification (CBP) had been performed or not. The levels
      of serum cytokines and intensive care unit (ICU) stay time, intubation time,
      mortality and ICU expenses were compared between the two groups. RESULTS: The
      levels of serum TNF-alpha, IL-6 and IL-8 rose, while that of IL-10 increased
      dramatically compared with normal values (all P<0.05). After CBP, the serum
      levels of TNF-alpha, IL-6 and IL-8 all dropped to certain extent and became lower
      than those before the treatment (all P<0.05). IL-10's serum level was not changed
      compared with that before treatment. Those who received CBP stayed in the ICU for
      a longer period compared with control group, and the ICU expenses increased
      evidently with significant differences (P<0.05 or P<0.01). However, there was no
      difference in mortality between the two groups. CONCLUSION: Under the effect of
      immunosuppressant in the post-OLT period, the excessive release of the anti
      inflammatory mediators may become dominant leading to imbalance between
      proinflammatory and anti-inflammatory mediators leading to MODS. CBP may remove
      serum proinflammatory cytokines to act as an effective supportive treatment.

PMID- 17207362
TI  - [p38 MAPK/cPLA2 pathway mediates interleukins release in inflammatory cell
      model].
AB  - OBJECTIVE: To explore the underlying mechanism of lipopolysaccharide (LPS)
      induced interleukin-1 beta (IL-1 beta) and IL-6 release via p38 mitogen-activated
      protein kinase (MAPK) pathway in HeLa cells for further identification of
      involved down-stream message factors. METHODS: HeLa cells were challenged with
      LPS to reproduce inflammatory cell model. The activity or expression of p38 MAPK,
      cytosolic phospholipase A(2) (cPLA(2)) and COX-2, was inhibited with pretreatment
      of inflammatory HeLa cells with the inhibitors (SB203580, AACOCF(3), NS-398) or
      transfected with the cPLA(2) antisense oligonucleotide (SK7111), then the
      activities and/or expression of p38 MAPK, cPLA(2), COX-2, and relationship with
      levels of IL-1 beta and IL-6 supernatants were determined in each group. RESULTS:
      SB203580 obviously down-regulated the activities of p38 and cPLA(2), as well as
      the release of IL-1 beta and IL-6. AACOCF(3) and SK7111 blocked dose-dependently
      the activity or expression of cPLA(2), IL-1 beta and IL-6 production. However,
      the expression of COX-2 could hardly be detected in HeLa cells, even after LPS
      treatment. At the same time, pre-treatment with NS-398 had no effect on IL-1
      beta, IL-6 production. CONCLUSION: p38 MAPK/cPLA(2) pathway mediates the
      expression of IL-1 beta and IL-6 resulting from LPS treatment of HeLa cells,
      while COX-2, as a down-stream enzyme of cPLA(2) has no effect in this process.

PMID- 17207363
TI  - [Analysis of 3,184 cases with acute mountain sickness complicated by multiple
      organ dysfunction syndrome].
AB  - OBJECTIVE: To investigate and analyze the probability of acute mountain sickness
      (AMS) [including high-altitude cerebral edema (HACE) and high-altitude pulmonary
      edema (HAPE)] complicated by multiple organ dysfunction syndrome (MODS) and its
      pathogenetic mechanisms. METHODS: Questionnaire survey was made to
      retrospectively study the hospitalization cases in the past 50 years, and the
      incidence of high-altitude MODS (H-MODS) were statistically analyzed to determine
      the main causes and pathogenic mechanism of MODS. RESULTS: Among 3 184 cases with
      severe AMS, 83 cases conformed to the diagnostic criteria of diagnosis of H-MODS,
      and the incidence was 2.6%. The pathogenesis of acute H-MODS might be related to
      the activation of inflammation pathways, activation of blood clotting pathways
      and the damage to gastrointestinal mucosa barrier. Therefore, improving the
      diagnosis and the treatment effects of H-MODS is an important measure to increase
      cure rate of AMS and to decrease its death rate. CONCLUSION: AMS complicated by
      multiple organ damage (MOD) is the main factor that influences the therapeutic
      efficacy. Prompt effective remedy on the spot is a significant measure to reduce
      incidence of MOD.

PMID- 17207364
TI  - [Reproduction of a rat model of disseminated intravascular coagulation
      accompanied by multiple organ injuries].
AB  - OBJECTIVE: To reproduce a rat model of disseminated intravascular coagulation
      (DIC) accompanied by multiple organ dysfunction syndrome (MODS) induced by
      endotoxin. METHODS: Twenty-four healthy Wistar rats were randomly divided into
      four groups: control group, low dosage lipopolysaccharide (LPS) group, middle
      dosage LPS group, and high dosage LPS group (each n=6). Rats of each group were
      given different dosages of normal saline (1.4 ml/kg, 2.8 ml/kg), low dosages LPS
      [1.4 mg/kg (56 microg/kg), 2.8 ml/kg (112 microg/kg)], middle dosages LPS [1.4
      mg/kg(98 microg/kg), 2.8 ml/kg (196 microg/kg)] and high dosages LPS [1.4 ml/kg
      (196 microg/kg), 2.8 ml/kg (392 microg/kg)] respectively twice 12 hours apart
      through femoral vein intubation injection. Blood platelet (PLT) count,
      coagulation function, D-dimer, fibrinogen (Fbg), antithrombin III (AT-III) blood
      glucose (Glu), biochemistry indexes including aminotransferase (AST), alanine
      transaminase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH)
      were determined before and after LPS challenge, and histopathologic changes of
      lung, liver and kidney were observed 4 hours after the second injection. RESULTS:
      The rats in high dosage LPS group died 4 hours later, and the rats in low and
      middle dosage LPS groups survived after double LPS challenge. The results of
      blood PLT, D-dimer, Fbg, Glu, AST, ALT, ALP, LDH, coagulation function of
      activated partial thromboplastin time, prothrombin time and level of anti
      thrombin III in middle dosage LPS group were significantly different compared
      with those of control group (P<0.05 or P<0.01). Obvious changes in histopathology
      were found in major organs such as lung, kidney and liver. CONCLUSION: Double
      intravenous LPS challenge (98 microg/kg and 196 microg/kg) in rats can reproduce
      a rat model with DIC accompanied by multiple organ injuries.

PMID- 17207365
TI  - [Evaluation of efficacy and safety of using molecular adsorbent recirculating
      system in the treatment of patients with chronic liver failure].
AB  - OBJECTIVE: To evaluate the effect and safety of a single treatment using
      molecular adsorbent recirculating system (MARS) on patients with chronic liver
      failure. METHODS: The effect of MARS artificial liver system in 60 cases of
      chronic liver failure was reviewed. The liver function, renal function, blood
      coagulation index, peripheral blood routine and serum electrolytes were
      determined before and after treatment with MARS. In 32 patients, side effects
      were looked for during MARS treatment and were observed. RESULTS: The levels of
      serum total bilirubin, direct bilirubin, non-conjugated bilirubin and total bile
      acid were significantly decreased respectively in patients after treatment with
      MARS for 8 hours (all P<0.05). There were no differences in the levels of serum
      albumin (ALB), globulin (GLB), blood routine, alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), prothrombin activity (PTA) and renal function
      before and after MARS treatment (all P>0.05). There were no significant
      differences in serum electrolytes indexes after MARS treatment except for carbon
      dioxide combining power (CO(2) CP). Vital signs were stable before and after the
      treatment. No significant side effects were observed. Thirty-two patients with
      MARS therapy were followed up for 1 month. Among them, 14 patients died within 1
      month (43.7%, 14/32 cases), while 18 patients survived (56.3%, 18/32 cases).
      CONCLUSION: MARS is one of the complementary methods that are safe and effective
      for patients with chronic liver failure.

PMID- 17207366
TI  - [Efficacy and safety of coupled plasma filtration adsorption combined with
      continuous veno-venous hemofiltration for multiple organ dysfunction syndrome
      patients with acute liver failure].
AB  - OBJECTIVE: To evaluate efficacy and safety of coupled plasma filtration
      adsorption (CPFA) combined with continuous veno-venous hemofiltration (CVVH) for
      the treatment of multiple organ dysfunction syndrome (MODS) patients with acute
      liver failure (ALF), and to evaluate the effect of CPFA plus CVVF on inflammatory
      mediators in these patients. METHODS: A total of 38 cases of 11 MODS patients
      with ALF (male 6, female 5) were treated with CPFA plus CVVH, and the following
      clinical indicators including changes in mean arterial pressure (MAP), oxygen
      index (PaO(2)/FiO(2)), tumor necrosis factor-alpha (TNF-alpha), interleukin-1
      beta (IL-1 beta), IL-6, IL-8, biochemical parameters of liver and kidney
      function, parameters of systemic inflammatory response syndrome (SIRS) score, and
      acute physiology and chronic health evaluation II (APACHE II) score were
      determined before and after the treatment. The degree of improvement in clinical
      symptoms, feasibility, tolerance toward CPFA plus CVVH, therapy-related adverse
      reactions and security were simultaneously evaluated. RESULTS: MAP increased by
      12 mmHg (1 mmHg=0.133 kPa), and PaO(2)/FiO(2) increased by 40 mmHg after the
      application of CPFA plus CVVH (both P<0.05), along with significant decrease in
      TNF-alpha, IL-1 beta, IL-6, IL-8 and markedly lowered levels of serum total
      bilirubin (IBIL), direct bilirubin (DBIL), blood urea nitrogen (BUN), serum
      creatinine (SCr) and blood ammonia (all P<0.05). Besides, clinical symptoms,
      including urinary volume, mental disturbance, jaundice, debility, nausea,
      vomiting, fever, abdominal distention, anepithymia, and SIRS, APACHE II scores
      were improved significantly after the CPFA plus CVVH (all P<0.05). No therapy
      related adverse reactions, including severe haemorrhage, shock, hypersensitivity,
      were noted, and patients tolerated well toward CPFA plus CVVH. The total survival
      rate of patients was 45.5% (5/11 cases) at the end of the treatment. CONCLUSION:
      Our data indicate that CPFA combined with CVVH is an effective and safe method to
      improve the prognosis of MODS patients with ALF, the mechanism of which may be
      related to its effective removal of inflammatory cytokines.

PMID- 17207367
TI  - [Changes in serotonin and noradrenaline in hepatic encephalopathy as a result of
      liver failure in rat].
AB  - OBJECTIVE: To investigate the changes in serotonin (5-HT) and noradrenaline (NA)
      in hepatic encephalopathy as a result of acute and chronic liver failure in rat.
      METHODS: One hundred and ten Sprague-Dawley (SD) rats were randomly divided into
      groups of normal control (n=20), experimental group of acute liver failure (ALF)
      encephalopathy (n=45), and experimental group of chronic liver failure (CLF)
      encephalopathy (n=45). Two dosages of thioacetamide (TAA) of 500 mg/kg were
      gavaged with an interval of 24 hours to reproduce ALF model. To reproduce CLF
      model rats were fed with 0.03% TAA in drinking water for 10 weeks, and 50% of TAA
      dosage was added or withheld according to the change in weekly body weight
      measurement. Animals were sacrificed and venous blood specimens were obtained
      after successful replication of model, and 5-HT, NA, ammonia, parameters of liver
      function were determined, and liver and brain were studied pathologically.
      RESULTS: The experiment showed that the liver functions of rats in groups ALF
      encephalopathy and CLF encephalopathy deteriorated seriously, changes in alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL),
      albumen (ALB), ALB/globulin (A/G), and blood ammonia were observed(P<0.05 or
      P<0.01). The clinical manifestations, liver and brain pathologies were identical
      to those of ALF and CLF encephalopathy. The values of 5-HT were increased in
      groups ALF encephalopathy and CLF encephalopathy [(16.06+/-1.08) micromol/L and
      (15.32+/-1.48) micromol/L] compared with the normal group [(2.75+/-0.26)
      micromol/L, both P<0.01], while the value of NA decreased in the group of CLF
      encephalopathy [(94.0+/-2.13) pmol/L vs.(121.2+/-14.8) pmol/L,P<0.05].
      CONCLUSION: The levels of 5-HT are elevated in the groups of ALF encephalopathy
      and CLF encephalopathy. The content of NA decreases remarkably in CLF
      encephalopathy.

PMID- 17207374
TI  - Stefano Delle Chiaie (1794-1860), a forerunner of osteoarticular paleopathology.

PMID- 17207375
TI  - Ultrasound imaging for the rheumatologist. VI. Ultrasonography of the elbow,
      sacroiliac, parasternal, and temporomandibular joints.
AB  - Ultrasound (US) examination of the elbow and parasternal joints is very useful to
      detect synovitis, degenerative changes, intrarticular calcification or soft
      tissue abnormalities. More recently new fields of research involving the
      sacroiliac and temporomandibular (TM) joints have evolved. Moreover, important
      information has been obtained about vascularization of the synovial joint in the
      sacroiliac region and structural modification such as internal derangement in the
      TM joint.. In this paper, we review and discuss the role of US in the evaluation
      of elbow, sacroiliac, parasternal and TM joint pathology.

PMID- 17207376
TI  - Cartilage oligomeric matrix protein (COMP) is modified by intra-articular
      liposomal clodronate in an experimental model of arthritis.
AB  - OBJECTIVE: High-dose liposomal bisphosphonates exert apoptotic effects. This work
      studies the chondroprotective and anti-inflammatory properties of intra
      articularly administered low-dose, non-cytotoxic liposomal clodronate. METHODS:
      Antigen induced arthritis in rabbits was treated with intra-articular injections
      of liposomal clodronate. Drug effects on cartilage oligomeric matrix protein COMP
      was assessed using immunohistochemistry and morphometry of synovial membrane and
      hyaline articular cartilage. RESULTS: COMP remained close to normal in liposomal
      clodronate treated superficial articular cartilage compared to a significant loss
      of COMP in arthritis controls treated with empty liposomes. The middle and deep
      layers of the hyaline articular cartilage were characterized by highly increased
      COMP expression in liposomal clodronate treated AIA joints compared to controls.
      In contrast to cartilage, synovial COMP expression was slightly decreased as a
      result of liposomal clodronate treatment. CONCLUSION: Low-dose, non-cytotoxic
      liposomal clodronate exerts a dichotomous effect on synovial membrane and
      articular cartilage COMP in the AIA model. COMP is a useful inflammation marker
      in the synovial tissue, but it also contributes to the structural integrity of
      the hyaline articular cartilage forming bridges between type II and IX collagens.
      Enhancement of COMP in clodronate treated AIA cartilage suggests a
      chondroprotective and anti-inflammatory effect in the inflammatorily damaged and
      mechanically strained cartilage.

PMID- 17207377
TI  - Central nervous system involvement as the presenting manifestation of autoimmune
      rheumatic diseases: an observational study using the American College of
      Rheumatology nomenclature for neuropsychiatric lupus.
AB  - OBJECTIVE: We sought to describe CNS involvement as initial presentation of
      autoimmune rheumatic diseases using a standardized nomenclature. PATIENTS AND
      METHODS: A 6-year observational study (1999-2005) was conducted in the University
      Hospital of Heraklion Crete, a regional referral secondary/tertiary care academic
      center. Patients presenting with new neurological symptoms of acute/subacute
      onset underwent clinical and laboratory screening for systemic autoimmune
      disorders. The diagnosis of an autoimmune rheumatic disorder was based upon the
      American College of Rheumatology (ACR) classification criteria, whereas for
      primary antiphospholipid syndrome (PAPS) we used the Sapporo preliminary
      criteria. In order to describe the neurological syndromes we used the ACR
      nomenclature for neuropsychiatric lupus. RESULTS: During this period fourteen
      patients (ten females and four males) were recorded. Eight patients had systemic
      lupus erythematosus (SLE), four had primary APS and the remaining two had
      systemic vasculitis. Four out of the eight SLE patients had secondary APS. Two of
      them presented with movement disorder (chorea). The other two and all four
      patients with primary APS presented with cerebrovascular disease (CVD). These six
      patients comprised the 5.7% of young adults under < 45 years old with
      cerebrovascular accident admitted over the 6-year period. CONCLUSION: SLE and APS
      either primary or secondary to SLE were the most common underlying systemic
      autoimmune rheumatic diseases, in patients presenting with a neurological event
      of acute onset. Young adults (< 45 years old) with CVD should undertake screening
      for SLE/APS.

PMID- 17207378
TI  - Association of tumour necrosis factor a, b and c microsatellite polymorphisms
      with clinical disease activity and induction of remission in early rheumatoid
      arthritis.
AB  - OBJECTIVE: To study the associations of tumor necrosis factor (TNF) a, b and c
      microsatellite markers with 1) the clinical disease activity and 2) the induction
      of remissions in patients with early rheumatoid arthritis (RA) treated with two
      treatment strategies. METHODS: In the FIN-RACo (FINnish Rheumatoid Arthritis
      Combination therapy) trial of two years, 195 patients with recent-onset RA were
      randomly assigned to receive either a combination (COMBI) (sulphasalazine,
      methotrexate, hydroxychloroquine, and prednisolone) or a single (SINGLE)
      (initially sulphasalazine with or without prednisolone) disease modifying
      antirheumatic drug (DMARD) therapy. TNF a, b and c microsatellite and HLA-DRB1
      typings were carried out in 165 (79 COMBI; 86 SINGLE) study completers. RESULTS:
      At baseline the 28 joint disease activity scores (DAS28) of the patients positive
      for TNFa2, a13 or b1 microsatellite markers were significantly higher than in the
      other patients. In the SINGLE patients the DAS28 improved comparably in patients
      with (n = 31) or without (n = 53) the TNFb1 marker (NS), while the DAS28 of the
      TNFb1-positive COMBI patients (n = 22) improved significantly more than that of
      the TNFb1-negative cases (n = 57) (p = 0.014). Respective 31.8% (7/22) and 28.1%
      (16/57) of the COMBI patients with or without TNFb1 allele achieved remission at
      one year. The corresponding figure in SINGLE patients were 0% (0/31) and 20.8%
      (11/53) (p = 0.006). At two years the remission frequencies in the TNFb1+/TNFb1-
      patients in the COMBI and SINGLE were 50.0%/38.6% and 9.7%/22.6%, respectively.
      CONCLUSION: Early TNFb1+ RA patients have more active disease but respond more
      favourably to COMBI treatment than the patients without this microsatellite
      allele. The finding may be of clinical relevance for the choice of DMARDs in
      early RA.

PMID- 17207379
TI  - Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1B gene polymorphisms
      in Turkish patients with rheumatoid arthritis.
AB  - OBJECTIVE: Interleukin 1 (IL-1) family is composed of two agonists, IL-1alpha and
      IL-1Beta and IL-1 receptor antagonist, IL-1Ra. The purpose of this study was to
      determine the relationship between polymorphisms of IL-1 receptor antagonist (IL
      1RN), IL-1B promoter and IL-1B exon 5 genes and susceptibility to rheumatoid
      arthritis (RA) in Turkish population. METHODS: Polymerase chain reaction (PCR)
      was used to determine the genotype of the IL-1RN for 94 RA patients and 104
      healthy controls. Genotyping of IL-1B polymorphisms at positions -511 (C/T) and
      +3953 (C/T) was detected by PCR followed restriction fragment length analysis.
      RESULTS: There was no significant difference in IL-1RN genotype and allele
      distributions between RA and the control groups. In addition, no significant
      association was observed in the allelic frequency (C or T) of IL-1B promoter (
      511) between RA patients and the controls (P = 0,118), but the genotype
      distribution of 1/2 (C/T) at position -511 showed a significant difference (P =
      0,038). Also, 2/2 genotype (T/T); (P = 0,028), and allele 2 (T) distribution (P =
      0,011) of IL-1B (+3953) showed significant differences between RA patients and
      the control groups in the study population. CONCLUSION: These results imply that
      2/2 (T/T) genotype or allele 2 (T) of IL-B (+3953) are susceptibility factors for
      RA in Turkey. Also, 1/2 genotype (C/T) of IL-1 -511 can play a protective role
      for RA.

PMID- 17207380
TI  - Incidence and clinical features of cytomegalovirus infection diagnosed by
      cytomegalovirus pp65 antigenemia assay during high dose corticosteroid therapy
      for collagen vascular diseases.
AB  - OBJECTIVE: To investigate the incidence and clinical features in patients with
      cytomegalovirus (CMV)-positive antigenemia during high dose corticosteroid
      therapy for collagen vascular diseases, and risk factors associated with it.
      PATIENTS AND METHODS: We examined retrospectively 35 consecutive patients for the
      presence of CMV-positive pp65 antigenemia. The patients were admitted to Saka
      General Hospital from 2000 to 2003, and were administered more than 0.5 mg/kg of
      body weight/day of peroral prednisolone for collagen vascular diseases.
      Characteristics of patients with and without CMV-positive antigenemia were
      compared. RESULTS: CMV-positive antigenemia was detected in 14 patients (40.0%),
      including six with microscopic polyangitis, three with rheumatoid arthritis, and
      five with other conditions. Three patients (8.6%) were diagnosed as having a CMV
      disease: pneumonitis or encephalitis. Symptoms and laboratory findings, including
      slight fever and a low increase in levels of hepatic enzymes and cytopenia, were
      observed in 10 of the 14 patients. Two patients died of CMV diseases refractory
      to ganciclovir. Ages of more than 70 years old were associated with the presence
      of CMV-positive antigenemia (relative risk = 4.5, 95% confidence interval = 1.14
      17.6). CONCLUSION: CMV infection diagnosed by CMV pp65 antigenemia assay is not
      rare during high dose corticosteroid therapy for collagen vascular diseases, and
      advanced age is considered a risk factor for it. It has a variety of symptoms and
      laboratory findings, which are mild and nonspecific to this type of infection,
      and they may not be clearly noted as clinical signs of CMV infection, even in
      patients with CMV diseases whose prognoses can be unsatisfactory. During high
      dose corticosteroid therapy for collagen vascular diseases, careful attention
      should be paid to CMV infection.

PMID- 17207381
TI  - Synovial inflammation in active rheumatoid arthritis and psoriatic arthritis
      facilitates trapping of a variety of oral bacterial DNAs.
AB  - OBJECTIVE: To investigate the presence of oral bacterial DNAs in serum and
      synovial fluid (SF) of patients with active rheumatoid arthritis (RA) and
      psoriatic arthritis (PsA). METHODS: Serum and SF samples from 16 RA patients, 14
      PsA patients, and 9 osteoarthritis (controls) patients were extracted for oral
      bacterial DNA. This was used in a checkerboard DNA-DNA-hybridization set up, to
      identify 40 different bacteria. RESULTS: Mean number +/- standard deviation (SD)
      of oral bacterial species in sera were 6.2 (3.2) in the RA group (p = 0.004) and
      5.4 (2.7) in the PsA group (p = 0.009) compared to 2.1 (1.7) in the controls.
      Periodontitis associated species Porphyromonas gingivalis and Prevotella
      nigrescens were exclusively detected in RA and PsA. Mean number (+/- SD) of oral
      bacterial species in SF were 14.0 (6.8) in the RA (p = 0.001) and 19.4 (7.1) in
      the PsA group (p < 0.001) compared to 4.0 (1.7) in controls. P. gingivalis,
      Tannerella forsythensis and Prevotella intermedia were exclusively identified in
      RA and PsA SF. Higher means of DNAs were found in RA SF compared to RA serum (p <
      0.001), and in PsA SF compared to PsA serum (p < 0.001). Higher concentrations of
      bacterial DNAs were found in RA and PsA compared to controls. CONCLUSION: Higher
      variety and concentrations of oral bacterial DNAs were found in SF compared to
      serum of RA and PsA patients. These findings indicate that synovial inflammation
      in RA and PsA may favor trapping of oral bacterial DNAs, suggesting a
      perpetuating effect of oral pathogens in joint disease.

PMID- 17207382
TI  - Imaging of intratendinous distribution of glucocorticosteroid in the treatment of
      Achilles tendinopathy. Pilot study of low-field magnetic resonance imaging
      correlated with ultrasound.
AB  - OBJECTIVE: Recently, a positive treatment effect of intratendinous injections of
      steroid in Achilles tendonitis (AT) has been described. Our aim was to test the
      localization and distribution of the injected steroid in both healthy (animal)
      tendons and in diseased human Achilles tendons. MATERIAL AND METHODS: Four pig
      tendons were injected in vivo and harvested. The harvested tendons were placed in
      0.2 Tesla MRI scanner, in order to select the optimal MRI sequences for tracking
      and localizing the bolus injection. Three patients with AT were treated with
      intratendinous steroid injection. Injections were placed in the pathologic areas
      of the tendon guided by ultrasound (US). MRI and US were performed at baseline
      and again immediately and 60 minutes after injection. A final follow-up MRI was
      performed 1 month after the injection. RESULTS: In the animal model, significant
      recoil of the injected substance was seen in all cases. In all three patients the
      injection was readily distributed within the tendon and no recoil through the
      injection channel was found. One-month follow-up showed a total regression of
      hyperaemia on US as well as regression of intratendinous oedema on MRI in all 3
      patients. CONCLUSION: It is possible to demonstrate the distribution pattern of
      injected steroid in diseased Achilles tendons by MR-imaging. In contrast to the
      recoil experienced in the healthy tendon of the animal, the lack of recoil of the
      injected volume through the injection channel in the sick human tendon may be
      caused by a derangement of the fibre structure, which allows the extra volume to
      be distributed within the lesion. This indicates that the effect on AT of intra
      tendinous injections of steroid is due to a local intra-tendinous action of the
      drug.

PMID- 17207383
TI  - Frequency of musculoskeletal conditions among patients referred to Italian
      tertiary rheumatological centers.
AB  - OBJECTIVE: To describe the occurrence of different rheumatic diseases and to
      examine the characteristics of patients referred to six Italian rheumatological
      units. To compare these data with those from other countries. METHODS: Six
      Italian rheumatological tertiary referral centers participated in the study.
      Diagnoses of in- and outpatients aged over 16 years were classified according to
      the International Classification of Diseases, ninth revision. RESULTS: Three
      thousand, five hundred and thirty-seven patients with mean age 56 +/- 14.8 years,
      of which 2604 (73.6%) were women, were studied. Inflammatory joint and spine
      diseases were diagnosed in 40.4%, connective tissue diseases in 14.4%,
      degenerative joint and spine diseases in 21.4%, soft tissue rheumatisms in 18.5%,
      and metabolic bone diseases in 5.3%. There was a significant difference among
      centers in the frequency of most diagnoses: non-academic centers cared for more
      patients with arthritis and connective tissue diseases and for less patients with
      degenerative diseases, soft tissue rheumatisms and metabolic bone diseases.
      Connective tissue diseases were constantly seen more often in Italian centers,
      whereas soft tissue rheumatisms were seen more often abroad. CONCLUSION: Our data
      emphasize the great variability of the diagnostic case-mix in different centers
      from the same country, an observation that raises some concerns of the results of
      descriptive multicenter studies. Studies on the breakdown of diagnoses made in
      rheumatological centers could be helpful to determine the burden of rheumatic
      diseases on the health system, and for the planning of health interventions by
      both the national rheumatological societies and health authorities.

PMID- 17207384
TI  - Sister chromatid exchanges and cell proliferative abilities in cultured
      peripheral blood lymphocytes of patients with rheumatoid and reactive arthritis.
AB  - OBJECTIVE: Analysis of cytogenetic alterations in peripheral blood lymphocytes
      (PBL) of patients with acute and chronic reactive arthritis (AcReA and ChrReA)
      and rheumatoid arthritis (RA). METHODS: The frequencies of sister chromatid
      exchanges (SCE) and cell proliferative abilities were analysed in PBL from 69
      patients with arthritis and 30 healthy controls. The analyses were done on
      metaphase chromosomes from PBL grown in cell culture for 72 hours. Cytogenetic
      parameters were compared among study groups and correlations with different
      clinical, immune and demographic characteristics were analysed. RESULTS: No
      significant increases in the frequencies of SCE were detected in PBL from
      patients with AcReA, ChrReA and RA as compared to controls. However, marked
      impairment of cell proliferative abilities was detected in cultured lymphocytes
      from patients with arthritis as compared to healthy controls. Significant
      associations between measures of disease activity and proliferative abilities of
      PBL were established. Parameters of lymphocyte proliferation were also influenced
      by concentration of anti-inflammatory cytokine interleukin-10 in the blood of
      patients. CONCLUSION: No increased risk of genetic alterations as measured by the
      rate of SCE was found in patients with RA and ReA. It is most likely that
      impaired proliferative abilities of peripheral blood lymphocytes are related to
      disease activity and could reflect systemic changes in cytokines production and
      intracellular signal transduction.

PMID- 17207385
TI  - Cardiovascular and pupillary autonomic nervous dysfunction in patients with
      rheumatoid arthritis - a cross-sectional and longitudinal study.
AB  - OBJECTIVES: Patients with inflammatory diseases often demonstrate autonomic
      nervous dysfunction. This study was initiated to investigate cardiovascular (CAD)
      or pupillary autonomic dysfunction (PAD) in patients with rheumatoid arthritis
      (RA). METHODS: Between 1997 and 1998, 33 RA patients were examined for
      characteristics, and parameters of CAD and PAD. In a longitudinal part of this
      study, thirty patients have been re-evaluated 8.3 +/- 0.1 yr later (response rate
      = 91%). RESULTS: A total of 18 patients (60%) demonstrated either CAD or PAD. The
      prevalence of CAD was 6/30 (20%) and the prevalence of PAD was 15/30 (50%). Of
      all cardiovascular tests, the Ewing test demonstrated the worst results (13/30
      patients were below the 5th percentile). Similar as in other diseases, several RA
      patients demonstrated autonomic nervous hyperreflexia with values above the 95 th
      percentile (relative variation coefficient: 7/30; respiratory sinus arrhythmia
      measure: 12/30; Valsalva measure: 1/30; Ewing measure: 0/30; latency time of
      pupillary light reflex: 5/30; maximal pupillary area: 0/30). During the 8-year
      observation period, 4/30 RA patients died. Non-survivors as compared to survivors
      had increased heart rate variation in the respiratory arrhythmia test (p= 0.038,
      hyperreflexia) but largely decreased heart rate variation in the Ewing test (p=
      0.009, hyporeflexia). Non-survivors as compared to survivors demonstrated more
      frequent pupillary autonomic dysfunction (100% vs. 42%, p= 0.035). CONCLUSION:
      This study demonstrates that CAD and PAD were frequent in patients with RA.
      Patients with a poor test result in the Ewing test and PAD might have an
      increased risk of death. This study in RA patients demonstrates similar results
      as in patients with diabetes mellitus.

PMID- 17207386
TI  - Activity of N-acetyl-beta-hexosaminidase and its isoenzymes in serum and synovial
      fluid from patients with different arthropathies.
AB  - OBJECTIVE: To evaluate the activity of N-acetyl-Beta-hexosaminidase (HEX) and its
      isoenzymes in the serum and synovial fluid of healthy volunteers and patients
      with an injury to the anterior cruciate ligament and/or meniscus (ACL)
      osteoarthritis (OA), juvenile idiopathic arthritis (JIA) and rheumatoid arthritis
      (RA). METHODS: The activity of HEX and its isoenzymes was determined according to
      Zwierz et al. method. Protein content was determined by the biuret method.
      RESULTS: The specific activity of HEX and its isoenzymes in the serum of patients
      with JIA showed a tendency to increase in comparison to the reference group. The
      specific activity of total HEX in the serum of RA patients was significantly
      increased in comparison to control. Our results show, that specific activity of
      HEX in synovial fluid, in the reference group 4.2 +/- 0.21 microkat/kg protein
      (0.25 unit/mg protein), is similar to activity in normal temporomandibular joint
      fluid (0.3 unit/mg protein). Therefore, we included this group in our research.
      In patients with OA and ACL injuries, HEX and its isoenzymes showed a tendency to
      increase in the specific activity in synovial fluid. The specific activity of HEX
      and its isoenzymes in the synovial fluid of patients with RA and JIA was
      significantly elevated in comparison to the control and the remaining groups.
      CONCLUSION: In the synovial fluid of patients with JIA and RA, the specific
      activity of HEX and its isoenzymes significantly increased in comparison to
      control and patients with diseases of a non-inflammatory etiology (OA and ACL).
      In the synovial fluid of control and diseased groups, HEX constituted a higher
      percent of total proteins than in serum.

PMID- 17207387
TI  - Restricted specificity of anti-ribosomal P antibodies to SLE patients in Israel.
AB  - OBJECTIVE: Anti-ribosomal P antibodies (aRib-P Ab) are highly specific for
      systemic lupus erythematosus (SLE), but their correlatation with disease activity
      and manifestations including renal, hepatic and central nervous system (CNS)
      involvement is still controversial. The aim of our study was to evaluate the
      prevalence of aRib-P Ab and their correlation with clinical manifestations and
      anti-dsDNA antibodies in SLE patients from Israel. METHODS: Elevated titers of
      aRib-P Ab utilizing the ELISA method were analyzed in 141 sera samples from 44
      SLE patients, 20 Familial Mediterranean Fever (FMF) patients, 22 primary
      antiphospholipid syndrome (PAPS) patients, 12 patients with infections, and 43
      healthy individuals. The SLEDAI score was utilized for assessing SLE disease
      activity. RESULTS: Elevated titers of aRib-P Ab were present in 11% of SLE
      patients (n = 6). The mean SLEDAI was 7 (range: 3-10). No statistically
      significant association was observed between the presence of aRib-P Ab and
      disease manifestations present in the SLEDAI. The 6 SLE patients had renal
      disease (n = 1), leucopenia (n = 1), rash (n = 3), and CNS involvement manifested
      as psychosis (n = 1) or depression (n = 1). Elevated titers of anti-dsDNA
      antibodies were found in 50% of patients with elevated titers of aRib- P Ab.
      Patients with PAPS, FMF, infections or healthy controls did not harbor elevated
      titers of aRib-P Ab. CONCLUSION: Elevated titers of aRib-P Ab were restricted to
      SLE patients. We confirm previously reported associations of aRib-P Ab reactivity
      with disease activity and elevated anti-dsDNA Ab titers. No significant
      correlation with a specific manifestation described on the SLEDAI score was
      established in this small cohort of patients.

PMID- 17207388
TI  - The serum levels of resistin in rheumatoid arthritis patients.
AB  - OBJECTIVE: Adipocyte-derived resistin is a circulating protein implicated in
      insulin resistance, but the role of human resistin is uncertain because it is
      produced largely by macrophages. The aim of this study was to analyze serum
      resistin concentrations in rheumatoid arthritis (RA) patients to determine the
      role of resistin in human inflammatory diseases. MATERIALS AND METHODS: Resistin
      concentrations were assessed by ELISA in serum samples from 42 patients with RA.
      Serum samples from 38 healthy subjects acted as controls. We also evaluated the
      circulating levels of tumor necrosis factor- alpha (TNF-alpha) and disease
      activity markers in RA patients. RESULTS: In RA patients, serum resistin levels
      were significantly higher than those in healthy subjects. Serum resistin levels
      in RA patients were correlated with the RA disease activity markers, CRP and ESR.
      Furthermore, resistin levels in RA patients were significantly correlated with
      circulating levels of TNF-alpha. CONCLUSION: Serum resistin levels were
      significantly increased in RA patients and correlated with inflammatory markers
      and TNF-alpha, suggesting that resistin may play a role in the rheumatoid
      inflammatory process.

PMID- 17207389
TI  - Circannual vitamin d serum levels and disease activity in rheumatoid arthritis:
      Northern versus Southern Europe.
AB  - BACKGROUND: Greater intake of vitamin D has been associated with a lower risk of
      rheumatoid arthritis (RA) and low serum vitamin D together with higher prevalence
      of RA seem common among North European people when compared to Southern Europe.
      OBJECTIVES: To evaluate serum 25-hydroxyvitamin D [25(OH)D] levels in female RA
      patients from North (Estonia) and South (Italy) Europe and to correlate them with
      the disease activity score (DAS28) during winter and summer. METHODS: Fifty-four
      RA Italian patients (IP) and 64 RA Estonian patients (EP) were evaluated for
      serum 25(OH)D levels in winter and summer time, as well as for DAS28 score.
      Normal female controls (C) were 35 (IC) and 30 (EC) age-matched subjects,
      respectively. 25(OH)D concentrations were measured by a competitive
      radioimmunoassay. Statistical analysis was performed by "r" Pearson correlation,
      "t" Student with Bonferroni correction and by repeated ANOVA measures (summer and
      winter) with two factors (country and clinical status). RESULTS: 25(OH)D levels
      were found significantly higher in IP versus EP (p = 0.0116) both in winter and
      in summer time. Differences were observed also in controls. The variations
      (increase) of 25(OH)D levels between winter and summer were found significant (p
      = 0.0005) in both IP and EP. Differences were observed also in controls. No
      significant differences were found concerning 25(OH)D levels between RA patients
      and their controls in either country. Interestingly, a significant negative
      correlation between 25(OH)D and DAS28, was found in summer only in IP (r =-0.57,
      p < 0.0001) and in winter in EP (r =-0.40, p < 0.05). CONCLUSION: Significantly
      lower 25(OH)D serum levels were observed in RA patients from North versus South
      Europe with a circannual rhythm in winter and summer time. In addition, 25(OH)D
      values showed a significant correlation (negative) with RA clinical status
      (DAS28) in both North and South European RA patients, suggesting possible effects
      of vitamin D among other factors on disease activity.

PMID- 17207390
TI  - Microscopic polyangiitis following recurrent Staphylococcus aureus bacteremia and
      infectious endocarditis.
AB  - Secondary vasculitis resulting from unusual pathologic expressions of infections
      has been described and has important clinical significance. Infectious agents
      have also been implicated in the pathogenesis of different primary systemic
      necrotizing vasculitides. Infectious endocarditis is of particular importance in
      the differential diagnosis of a patient presenting with ANCA associated
      vasculitis. We report a well-documented case of a patient with recurrent
      Staphylococcus aureus bacteremia who developed bacterial endocarditis and also
      fulfilled the Chapel Hill Conference definitions for microscopic polyangiitis. To
      the best of our knowledge, it is the second case of bacterial endocarditis
      associated with both pANCA and anti-MPO specificity that fulfilled definitions
      for systemic necrotizing vasculitis. We emphasize the potential pathogenic role
      of infection as the trigger factor for the development of systemic vasculitis.

PMID- 17207391
TI  - Molecular mechanisms in normal pregnancy and rheumatic diseases.
AB  - Pregnancy is a phenomenon that is not totally understood, based on the complex
      molecular interactions between the mother and the embrio. Once the fecundation is
      completed the fetus starts to fight for survival. The first challenge is the
      implantation process and the second one is the interaction with the maternal
      immune system. This review discusses how the fetus avoids the immune system
      rejection, and the mechanisms that the maternal immune system adapts in order to
      be fit for a successful pregnancy. Also, we focus in this paper on the effects of
      pregnancy in rheumatic diseases, because the myriad clinical outcomes of the
      disease itself and the obstetric complications dependent of the disease
      implicated, as for example in rheumatoid arthritis (RA), systemic lupus
      erythematosus (SLE), spondyloarthropaties and antiphospholipid syndrome (APS).

PMID- 17207392
TI  - Design and validation of a new scale to assess the functional ability in children
      with juvenile idiopathic arthritis (JIA).
AB  - OBJECTIVE: The assessment of the functional ability is one of the items of the
      core set to define improvements in patients with JIA, CHAQ being the most used
      scale already validated in 32 countries. The aim of this study was to design and
      validate a new scale named CAPFUN (capacidad funcional = functional ability) to
      assess functional ability in children with JIA. METHODS: This scale includes 20
      items, 8 of upper limbs, 8 of lower limbs, 3 combined, and 1 of cervical spine,
      developed in two steps according with OMERACT. Each item is scored: 0 when it is
      impossible to be performed, 1 when it is performed incompletely or with
      difficulties, and 2 when it is well performed. Seventy three patients with JIA
      according to ILAR criteria were assessed: 25 boys (34.2%) and 48 girls (65.8%)
      whose aver-age age was 12.8 years (95% CI 11.8 - 13.8) and the time from disease
      onset was 5.02 years (95% CI 3.9 - 6.1). For validation purposes, it was applied
      to 91 healthy children and adolescents. In every patient, correlation with active
      joints count and functional class according to Steinbrocker was assessed and with
      CHAQ in 31 patients in this series. RESULTS: The CAPFUN index obtained in all
      healthy children was 2. Patients' media CAPFUN index was 1.54 (95%CI 1.38 -
      1.68). The CAPFUN index for Steinbrocker's class I was 1.84 +/- 1.8; for class II
      1.60 +/- 1.5 and for class III 0.91 +/- 1 (F 24.1 p < 0.001). CAPFUN showed
      significant correlation with CHAQ (Spearman coefficient -0.79 p < 0.001), with
      active joints count (Spearman coefficient -0.72 p < 0.001) and with Steinbrocker
      functional classes (Spearman coefficient -0.69 p < 0.001). This scale showed a
      good internal reliability (alpha coefficient equal to 0.94), its construct
      validity is demonstrated by its good correlation with Steinbrocker's scale and
      with CHAQ. CONCLUSION: CAPFUN is a new instrument in order to assess functional
      ability in children with JIA. This scale showed a good internal reliability.
      Construct validity is demonstrated by its high correlation with Steinbrocker's
      scale and with CHAQ. This study demonstrates the usefulness of CAPFUN for the
      assessment of functional ability in children with JIA.

PMID- 17207393
TI  - Bilateral renal artery stenosis in Kawasaki disease: a report of two cases.
AB  - We report two cases, a boy and a girl, who developed severe renal hypertension
      over sub-acute phase of Kawasaki Disease (KD). Paediatricians should be alert to
      consider preceding KD as potential source of secondary hypertension in young
      infants, and raised blood pressure should be regarded as a life-threatening
      complication in all KD children.

PMID- 17207394
TI  - A case of rheumatoid arthritis complicated by two different types of
      lymphoproliferative disorder.

PMID- 17207395
TI  - Mycobacterium fortuitum infection complicating infliximab therapy in rheumatoid
      arthritis.

PMID- 17207396
TI  - Effects of intra-articular hyaluronic acid and corticosteroid therapies on
      articular cartilage in experimental severe osteoarthritis.

PMID- 17207397
TI  - [Poverty, inequality and power: health as a human right].

PMID- 17207398
TI  - [Pleura's solitary fibrous tumor. Clinical pathology analysis of 17 cases].
AB  - INTRODUCTION: Solitary fibrous tumor of the pleura (SFTP) is a rare neoplasm that
      usually originates from the visceral pleura, but it can occur in a wide range of
      tissues. Approximately 12% of pleural cases are malignant tumors and surgical
      excision usually become curative. The objective of this study is to present 17
      new cases of SFTP and analyze the morphological characteristics that help to
      identify tumors with a malignant behavior. MATERIAL AND METHODS: We did a
      retrospective review of the patients who had primary pleural tumors from January
      1995 to August 2005. RESULTS: Among a total of 94 primary pleural tumors, 17
      patients were enrolled in this study, 8 men and 9 women, with a mean age of 63
      years. Thirteen cases (76%) were benign and four cases (23%) were malignant.
      Local recurrences occurred in three cases. There were no metastases found.
      Recurrences occurred only in malignancy tumors. All malignant tumors were high
      cellularity and had hemiangiopericitic pattern, more than 4 mitoses per 10 high
      power fields, and moderate to marked polymorphism. CONCLUSIONS: SFTP shows a
      benign biologic outcome in most of the cases. There are some histological
      characteristics that led to distinguish between benign and malign neoplasm.

PMID- 17207399
TI  - [Prevalence and functional impact of arthropathies in elderly adults].
AB  - INTRODUCTION: Musculoskeletal disorders are public health issues in the entire
      world; their impact seems to be higher on elderly people. OBJECTIVE: To establish
      the prevalence and the functional impact of arthropathies on the elderly people
      from Merida, Yucatan, Mexico. MATERIAL AND METHODS: The SABE-PAHO survey was
      administered to a random sample of people older than 60 Merida, Yucatan, Mexico.
      Arthropathy was evaluated by self report; on the other hand, physical function
      was evaluated using the modified Katz's scale (basic activities of daily living,
      BADL) and the Lawton's scale (instrumental activities of daily living, IADL).
      RESULTS: 1747 patients (68.6% females, 31.4% males), aged 71.5 +/- 8.5 years old,
      were studied; 498 (28.5%; 95% CI = 26.4 to 30.6) had arthropathy. After logistic
      regression and adjustment for chronic obstructive lung disease, ischemic
      cardiopathy, and stroke presence or to be older than 80 were performed,
      arthropathy was found associated to BADL (p=0.03) as well to IADL (p=0.04)
      impairment. CONCLUSIONS: The prevalence of arthropathy in elderly people from
      Merida, Mexico, was 28.5%, it was found to be independently associated to
      impairment for BADL and IADL.

PMID- 17207400
TI  - [Depression prevalence and risk factors found in women attended by a family
      physician].
AB  - OBJECTIVES: Determine the prevalence of depressive symptoms in adult woman who
      was attended by family physician, to explore risk factors for depression and
      estimate how often depression is registered as a diagnosis by the family
      physician. MATERIALS AND METHODS: We did a prospective, analytic, and transversal
      study with simple randomized sampling at a Mexico City Family Medicine Clinic
      from March to December 2004. The size of the study was 384 patients. It includes
      women from 20 to 59 years of age. We excluded women without a clinical file for
      at least 1 year of reliable information. The Center for Epidemiologic Studies
      Depression Scale (CES-D) and the Family Apgar Scale were applied. RESULTS: The
      survey included a total of 400 patients with the following characteristics:
      average age, 39 +/- 11 years; married, 74%; homemakers, 68%, and women with
      education level of high school or less were 79%. Prevalence of depressive
      symptoms was 52% (95% confidence interval [95% CI], 47-57). In women between 20
      and 39 years of age, there was an association between depression and family
      dysfunction; the average number of healthcare appointments for the year prior to
      the study was significantly higher in patients 40 years old or more. CONCLUSIONS:
      There is a high prevalence of depressive symptoms in adult women, and depression
      diagnosis is frequently omitted. Depression-associated factors differ according
      to chronological age. In young women, family dysfunction is the main risk factor.

PMID- 17207401
TI  - [Chronic complications of diabetes mellitus. What is the prevalence of diabetes
      in a family medical unit?].
AB  - INTRODUCTION: The role of the family doctor in fundamental in the prevention of
      diabetic complications, because these complications will be minor if there is
      good glycemic control during life. OBJECTIVE: Determine the frequency of late
      complications of diabetes mellitus (DM) among IMSS-insured population in Ciudad
      Obregon, Sonora, Mexico. MATERIALS AND METHODS: A retrospective analysis included
      252 diabetic patients selected by a systematized and stratified randomized
      sampling including all patient files available in the Family Medicine Unit 1 in
      Ciudad Obregon, Sonora. The information was taken from the clinical charts got by
      family physicians and specialists. We used descriptive statistics and correlation
      of Pearson looking for the association between glicemia's level and enough time
      to produce complications. RESULTS: Arterial hypertension was found in 168 cases
      (67%), hypertriglyceridemia in 148 (59.4%), neuropathy in 106 (42.6%),
      hypercholesterolemia in 89 (35.7%), retinopathy in 69 (27.5%), nephropathy in 51
      (20.5%), diabetic foot in 27 (10.8%), ischemic cardiopathy in 25 (10%), cerebral
      thrombosis in 11 (4.4%). The period between DM diagnosis and the appearance of
      complications was 3.2 to 13.1 years. The correlations were high and significant
      in every complication. CONCLUSIONS: The frequency of DM complications in this
      study was very high, with an increasing tendency of developing complications
      throughout the time.

PMID- 17207402
TI  - [Non-satisfaction medical doctors during pediatric training. Prevalence and
      associated factors].
AB  - INTRODUCTION: The prevalence of medical discontent is approximately 4%. Factors
      such as gender, age, type of specialization, disillusion with the profession and
      economical factors have been identified among graduated medical doctors.
      Residents mentioned educational strategies as an additional factor of discomfort.
      OBJECTIVE: To identify the prevalence and factors that influence on resident's
      discontent during their pediatric training program. MATERIAL AND METHODS: The
      principal motives of dissatisfaction during the period of training in pediatric
      residence were identified using the semantic nets technique. RESULTS: Prevalence
      of dissatisfaction was 3.1%. The principal motives were: educational strategies,
      duration of medical career, work overload, hierarchical systems and abuse.
      CONCLUSIONS: Prevalence of dissatisfaction during a medical residence is similar
      to that reported in graduated pediatricians, and occurs during the first two
      years of residence. Educational strategies were one of the principal causes of
      discontent, and other local factors such as work overload, jeriarquical systems
      and abuse were identified.

PMID- 17207403
TI  - [Attention of crashed patients hurt on the road].
AB  - OBJECTIVE: To describe main factors that are important in the attention of
      crashed patients, in emergency services in Cuernavaca, Morelos, Mexico. MATERIAL
      AND METHODS: A cross-sectional study that included all people hurt on the road
      that were attended on emergency services between February and April of 2001. The
      emergency services of the following hospitals were used: Hospital General
      Regional 1 of the IMSS, Hospital General "Jose G. Parres" of the SSA, and two
      private hospitals, located in Cuernavaca city. The variables were social
      demography, related to the crash event and the injury that needs medical
      attention; and dependent variable was the opportunity for the attention.
      Different kinds of analysis were applied, such as simple, bivaried and of
      multiple logistic regressions. RESULTS: 382 cases were recorded, 72.2% of them
      were male victims and the average age was young-adults. The traffic accidents
      were the main cause of these lesions. Emergency medical attention was required
      mainly on weekends (57.3%). The main anatomic regions hurt were (46.3%) the head,
      face and neck; 56% of the wounds were minor, 41.1% of the wounds were serious or
      severe and only 2.9% of them were extremely severe. The time for attention on the
      emergency services on Cuernavaca was too long. It was an average of one hour and
      56 minutes for serious or severe wounded victims and one hour and 48 minutes for
      extremely severe wounded victims, and therefore they didn't meet the optimal
      standard time. The factors associated with opportune medical attention were: high
      level of education and age, as well as the use of an ambulance to be transported
      to the hospital and require hospitalization. The severe of the wounds had no
      influence. CONCLUSIONS: The final model show different social demographic factors
      as age, level of education and the opportune medical attention. Therefore it is
      clear that there is not a well emergency system between the different hospitals
      to provide opportune and effective medical attention.

PMID- 17207404
TI  - [Alternative methods for development of institutional teachers: more than the
      goals].
AB  - INTRODUCTION: The Instituto Mexicano del Seguro Social faces some problems and
      one of them is to promote research in health area, and development of teachers
      and researchers. With the support of the Fondo de Fomento a la Investigacion
      (FOFOI) a project was developed through professors in order to create the
      Methodological Diplomat in Teaching First Level in those delegations that do not
      have a Centro de Investigacion Educativa y Formacion Docente (CIEFD) with the
      intention of have an alternative program for the institutional professors.
      MATERIAL AND METHODS: Intervention study comparing before and after the
      interventions inside each group and among the groups of professors who are in the
      program Diplomat in Teaching First Level with different systems: a) full time at
      the CIEFD; b) program at distance with the help of tutors. Three dependent
      variables were explored: development of a position about education; critical
      theoric reading texts in education and critical reading of research reports in
      education. RESULTS: In the development of a position about education all the
      groups had an improve that was statistically significant (Wilcoxon < 0.05); in
      the critical reading of theoric texts in education there were also significant
      differences, and the same encouraging results were observed in critical research
      reading reports in education (Wilcoxon < 0.05). CONCLUSION: Under controlled
      circumstances, the program at distance with a visitor teacher is an adequate
      alternative for the formation of institutional professors.

PMID- 17207405
TI  - [Overweight and obesity in health team of a family medicine unit].
AB  - INTRODUCTION: The overweight and obesity are important public health problems in
      Mexico and around the world because it has been a progressive growth. OBJECTIVES:
      To identify the frequency of overweight and obesity in heath workers at a family
      care unit in the Mexican Institute of Social Security. MATERIAL AND METHODS: A
      descriptive, glimpsing and transversal study was done. In this study were
      included 207 workers between them were family doctors, gastroenterologists,
      nurses, medical assistants, social workers and laboratory workers. All of them
      were personnel of the health care unit and they were follow from January to
      February 2001. The body mass index was measured (kg/m(2)) on all of them and the
      results are the following: RESULTS: There were overweight and obese in 46% of
      them; the results showed that males were more affected (54%) in comparison with
      studies in Mexican adult in general population. According to age, people 50 years
      old or more were most affected (57%). According with the kind of health job that
      they do, the laboratory workers got 64%, family doctors and gastroenterologist
      got 58%, they were the most affected groups. CONCLUSIONS: Overweight and obesity
      were frequent in heath care workers. This research shows a higher frequency of
      obesity in men compared with the studies of general adult population in Mexico.
      It is necessary to apply health care programs to improve life style and nutrition
      between health workers as well as fit programs.

PMID- 17207406
TI  - [Social politics against poverty and in favor of health in Mexico].
AB  - One of the biggest challenges that Mexico faces is to fight against the poverty.
      The transition of a characteristic welfare model from the government in a closed
      economy, to an open economy where the functions of the State are limited, has
      modified the modalities of the social politics against poverty. Six indispensable
      conditions are identified for poverty's reduction: 1. Economic development with
      stability in order to generate more and better jobs for poor people. 2. To
      improve regional economies. 3. To improve home conditions of poor people. 4. To
      elevate education levels (to encourage an authentic heath education). 5. To
      diminish catastrophic expenses for health problems. 6. Technical training for all
      workers. The impact of poverty over health can provide valuable elements to
      establish effective preventive strategies on health workers.

PMID- 17207407
TI  - [Meiotic and parental origin of extra chromosome 21 in children with regular
      trisomy 21].
AB  - INTRODUCTION: Down syndrome (DS) or trisomy 21 is the most common chromosomal
      abnormality in live birth children. Most cases are regular trisomies 21 secondary
      to a maternal non-disjunction (ND). Meiotic and parental origins have been
      recently investigated by segregating genetic markers from DNA hypervariable
      regions. OBJECTIVE: To identify the meiotic and parental origin in children with
      regular trisomy 21. MATERIALS AND METHODS: There were analyze 20 groups of three
      (every group included parents and child with Down syndrome). There were used
      soothe following markers: D21S11, D21S1260, and D21S265. RESULTS: The ND occurred
      during the first meiotic division (M1) in 13 cases and at the second meiotic
      division (M2) in the other seven. Twelve out of the 13 NDs from the first group
      were maternal and one paternal. The parental origin within the M2 group was not
      elucidated. CONCLUSIONS: Meiotic origin was identified in all cases. As in other
      reports, the origin of trisomy 21 in the present population is mainly secondary
      to a maternal ND in M1.

PMID- 17207408
TI  - [Neurosarcoidosis. Report of one case in Mexico].
AB  - INTRODUCTION: The sarcoidosis is a granulomatous, multisystemic disease, of
      unknown etiology that mainly affects the lungs, skin and lymphatic ganglia. The
      definitive diagnosis is made by the presence of granulomas non-caseous in diverse
      organs. Sarcoidosis is rare in Mexico and reports of its incidence do not exist.
      In Spain the incidence is low (1.2 to 1.5 cases by 100,000 inhabitants). In the
      United States incidence is 5.9 to 6.3 cases by 100,000 inhabitants (males and
      females respectively). Neurosarcoidosis is present in 5 to 26% of all the
      patients with sarcoidosis. The neurological manifestations are diverse, depending
      on the location site. CLINICAL CASE: We present the case of a male 33 years old,
      with recurrent facial paralysis, optic neuritis and affection of the third
      cranial nerve; the tomography of skull reveled an grow of left cavernous sinus
      and reinforcing bilateral temporal giral, and the nuclear magnetic resonance
      showed leptomeningeal reinforcing in the temporal lobe. CONCLUSION: Although the
      neurosarcoidosis is rare in Mexico, it should be considered in patients with
      suggestive clinical manifestations and compatible imaging findings. It should be
      done an intense search of systemic affection with biopsy and verification of non
      caseous granulomas.

PMID- 17207409
TI  - [Irritable bowel syndrome in adults attending to medical offices at UMF].
AB  - OBJECTIVE: To determine the prevalence of irritable bowel syndrome (IBS) in
      adults between 20-49 years of age that are attended at a medical offices at UMF
      53 of the IMSS, Leon, Guanajuato. MATERIAL AND METHODS: All adult patients
      between 20-49 years old that attended medical offices at UMF 53 were carried out
      a survey to diagnose SII according to the approaches of Rome II. RESULTS: 246
      patients were studied, 85 patients (35%) had a diagnosis of IBS. Of those 85
      patients, 8 patients (9%) had IBS with prevalence of diarrhea, 41 patients (48%)
      to the subgroup of IBS had prevalence of constipation and 32 patients (42%) with
      IBS had alternating symptoms; 18 patients (21%) they were men and 67 patients
      (79%) were women. CONCLUSIONS: Prevalence of IBS in adults between 20-49 year-old
      attending to medical offices at UMF 53 of the IMSS, Leon, Guanajuato, is of 35%,
      being more frequent the IBS with constipation.

PMID- 17207410
TI  - [IMSS in numbers. Evaluation of the performance of health institutions in Mexico,
      2004].
AB  - The evaluation of health institutions performance in Mexico during 2004 was done
      using 29 indicators that describe intra-hospital mortality rates, productivity of
      health services, availability of health resources, quality of care, security,
      investment and costs of health care and the satisfaction level by users of health
      services. This exercise describes the efficiency and organization of health
      services provided by the different health institutions and allows comparing and
      balancing the performance of each institution. Results indicate the differences
      in availability of resources, inequity in the financing health care services, and
      inefficiency in the use of resources but also describe the level of efficacy of
      certain institutions and the satisfaction level that different users have of
      health services. The evaluation of the performance of the entire health
      institutions should provide the means to improve all the process of health care
      and to increase the quality of care in all health institutions in the country.

PMID- 17207411
TI  - Evaluation of synthetic polymeric micelles as a stabilization medium for the
      handling of membrane proteins in pharmaceutical drug discovery.
AB  - PURPOSE: Polymeric micelles have been used for solubilization of insoluble drugs
      and as carriers for drug delivery applications. Here we evaluated an application
      of the synthetic polymeric micelles in experiments designed to improve the
      handling and stability of membrane proteins targets. METHODS: Particle sizing by
      dynamic light scattering was performed in a Zeta Plus Photon Correlation
      Spectrometer at 532 nm. UGT1A1 activity has been measured in fluorescent assay
      using scopoletin as a substrate. COX-2 activity has been measured in a
      fluorescent assay using Amplex Red. Fluorescence Resonance Energy Transfer (FRET)
      was monitored using either 463 nm excitation wavelength (the emission range 500
      600 nm) or 395 nm excitation wavelength (the emission range 500-600 nm). RESULTS:
      Incorporation of membrane proteins into PreserveX-QML polymeric micelles resulted
      in improved homogeneity and stability of the preparation and in reduced light
      scattering. Stabilization of the biological activity of micelle-incorporated
      membrane proteins, such as the human UGT1A1 and COX-2 both during extended
      incubations at room temperature and during multiple freeze/thaw cycles, has been
      achieved. CONCLUSION: PreserveX-QML polymeric micelles help to homogenize and
      disperse membrane proteins preparations and stabilize the biological activity of
      the proteins making it more suitable for pharmaceutical assays and applications.

PMID- 17207412
TI  - Anti-hyperlipidemic and hypoglycemic effects of Gynostemma pentaphyllum in the
      Zucker fatty rat.
AB  - Gynostemma pentaphyllum is a traditional Chinese medicine used for a variety of
      conditions, including elevated cholesterol. We have examined the pharmacological
      anti-hyperlipidemic and hypoglycemic effectiveness of Gynostemma pentaphyllum in
      the obese Zucker fatty diabetic rat model. After treatment for 4 days Gynostemma
      pentaphyllum 250 mg/kg reduced triglyceride (33%), total cholesterol, (13%) and
      low density lipoprotein cholesterol levels (33%). These effects were dose
      dependent and maintained for at least 5 weeks. Chronic treatment for 3-5 weeks
      also reduced post-prandial hypertriglyceridemia induced by olive oil 10 mg/kg in
      the Zucker fatty rats but had no significant effect in lowering sucrose-induced
      hyperglycemia in Sprague-Dawley rats. A novel regulation by Gynostemma of glucose
      levels was also observed in the Zucker fatty rat model. In a glucose tolerance
      test in obese and lean Zucker rats pretreatment with Gynostemma pentaphyllum 250
      mg/kg demonstrated glucose levels were significantly less 2 hours post challenge
      (20%) in the Gynostemma pentaphyllum obese rats compared to the control group.
      Gynostemma pentaphyllum did not significantly reduce glucose levels at 120 min in
      the lean strain, in contrast to the 20% decrease seen in the obese rat. In vitro,
      Gynostemma pentaphyllum inhibited alpha-glucosidase activity (50% inhibition at
      42.8), which compared to acarbose (50% at 53.9 microg/mL). The improvement in
      glucose tolerance at 120 min by Gynostemma pentaphyllum in obese Zucker fatty
      rats but not lean rats suggests that it may improve insulin receptor sensitivity
      and together with the significant reduction of hypertriglyceridemia, cholesterol
      and low density lipoprotein cholesterol suggests that Gynostemma should be
      examined further by oral hypoglycemic/anti-hyperlipidemic therapy.

PMID- 17207413
TI  - Drug disease interactions: role of inflammatory mediators in depression and
      variability in antidepressant drug response.
AB  - Increased cytokine expression and concurrent psychiatric symptoms were initially
      observed after administration of cytokines to patients afflicted with cancer,
      hepatitis and multiple sclerosis. Cytokines are a diverse group of soluble
      messenger proteins involved in the regulation, repair of cells, and control of
      immune events. During an inflammatory event expression of CD4+ T-lymphocyte
      helper (Th)1 cells that primarily produce pro-inflammatory cytokines is favored
      which can lead to development of inflammatory disease (e.g., cardiovascular
      disease). Similarly, relationships have been shown to exist between changes in
      inflammatory mediator concentrations, specifically pro-inflammatory cytokines,
      and depression. An increased prevalence of depression in patients afflicted with
      co-morbid inflammatory disease indirectly supports this association. In further
      support, antidepressants have been suggested to alleviate symptoms of depression
      via anti-inflammatory actions. Administration of anti-cytokines to patients with
      concurrent depression and inflammatory disease has resulted in relief of
      depressive symptoms. The exact role of inflammation in development of depression,
      however, remains to be determined. Nevertheless, increased expression of
      inflammatory mediators in depressed patients occurs which may lead to variability
      in response to antidepressant drug therapy. For example, depressed patients non
      responsive to drug treatment are reported to have increased cell mediated
      immunity shown by elevated CD4+ T-cell activity, pro-inflammatory cytokine
      expression, and stimulation of the acute phase response. This suggests a psycho
      neuroimmunological approach may be required for optimal pharmacotherapy.

PMID- 17207414
TI  - Evaluation of in vitro-in vivo correlation and anticonvulsive effect of
      carbamazepine after cogrinding with microcrystalline cellulose.
AB  - PURPOSE: Carbamazepine is a poor water soluble drug and its bioavailability is
      limited by dissolution rate. Dissolution, serum concentration and anticonvulsive
      effect of the drug have been evaluated after cogrinding with microcrystalline
      cellulose. A cogrinding technique was used to increase the dissolution, serum
      concentrations and anticonvulsive effect of the drug. A novel deconvolution
      technique of in vitro in vivo correlation was evaluated. METHODS: The drug
      coground with microcrystalline cellulose, the corresponding physical mixture,
      unground and ground drug powder were subjected to dissolution measurement.
      Coground and unground drug serum concentrations were investigated in rabbits.
      Also the anticonvulsive effects of the latter preparations were assessed in mice.
      For elucidation of observed in vitro and in vivo differences FT-IR spectroscopy,
      X-ray diffraction patterns and DSC thermograms of the preparations were studied.
      RESULTS: The dissolution of the coground was the highest (percent dissolved in
      the first 20 minutes, %D20', was 97.5). The unground drug powder exhibited the
      lowest dissolution (%D20'=40). The difference was reflected in their
      corresponding area under the mean serum concentration curves between 0-16 hr
      (118.96 vs 54.17 microg x hr/ml) as well as protection abilities against
      strychnine and electrically induced seizures. The onset of tonic seizures induced
      by strychnine was increased between 40-140% in the case of the coground system
      depending on dose and time of carbamazepine administration. CONCLUSION:
      Cogrinding was an effective technique in increasing carbamazepine dissolution due
      to reduced crystallinity as seen in X-ray pattern, enhanced wettability and
      decreased particle size, which in turn resulted in increased serum concentrations
      and its anticonvulsive effect. A novel simple deconvolusion technique not
      requiring intravenous data denoted as the double reciprocal area method was used
      to establish correlation between in vitro and in vivo parameters.

PMID- 17207415
TI  - Expanding the scope of crystal form evaluation in pharmaceutical science.
AB  - The commentary seeks to provide a brief history and perspective on the importance
      of crystal forms of pharmaceuticals as a means of achieving performance criteria.
      The expanding scope of crystal form selection, emergence of crystal engineering
      in pharmaceutical science and pharmaceutical co-crystals are topics of this brief
      review.

PMID- 17207416
TI  - Multiparticulate formulation approach to colon specific drug delivery: current
      perspectives.
AB  - Colon specific drug delivery has gained increased importance not just for the
      delivery of drugs for the treatment of local diseases associated with the colon
      but also as potential site for the systemic delivery of therapeutic peptide and
      proteins. To achieve successful colon targeted drug delivery, a drug needs to be
      protected from degradation, release and/or absorption in the upper portion of the
      GI tract and then ensure abrupt or controlled release in the proximal colon. Drug
      modifications through covalent linkages with carrier or prodrug approach and
      formulation based approaches can be used for colonic delivery. Report suggests
      that drug carrier systems larger than 200 mm possess very low gastric transit
      time due to physiological condition of the bowel in colitis. And for this reason
      and considering the selective uptake of micron or sub-micron particles by
      cancerous and inflamed cells/ tissues a multiparticulate approach based on
      pellets, granules, microsphere or nanoparticle type formulation is expected to
      have better pharmacological effect in the colon. The review is aimed at
      understanding recent advancements made in multiparticulate formulation approach
      for colon specific delivery of medicaments.

PMID- 17207417
TI  - Applications of thermo-reversible pluronic F-127 gels in pharmaceutical
      formulations.
AB  - It is, sometimes, desirable to maintain a constant plasma drug concentration
      within the therapeutically effective concentration range. The use of high
      viscosity hydromiscible vehicles such as hydrophilic gels, is one of various
      approaches for controlled drug delivery, and represents an important area of
      pharmaceutical research and development. Of these systems, Pluronic F-127 (PF
      127) provides the pharmacist with an excellent drug delivery system for a number
      of routes of administration and is compatible with many different substances.
      Gels containing penetration enhancers have proven to be especially popular for
      administering anti-inflammatory medications since they are relatively easy to
      prepare and very efficacious.

PMID- 17207418
TI  - Single dose pharmacokinetics and bioavailability of butyryl glucosamine in the
      rat.
AB  - PURPOSE: To study single dose pharmacokinetics and bioavailability of the
      synthetic glucosamine analogue, N-butyryl glucosamine (GLcNBu) after different
      routes of administration, and also the effect of food following oral doses of
      GLcNBu in the rat, and stability and absorption of GLcNBu across the rat everted
      intestine. METHOD: GLcNBu was administered intravenously (i.v.),
      intraperitoneally (i.p.) and orally. Effect of food was studied following oral
      administration only. Single doses of 223 mg/kg were administered in all cases.
      Serial blood samples were collected from the jugular vein for GLcNBu
      determination. Everted excised rat intestine segments were suspended in Tris
      buffer at 37 degrees C and samples collected from both serosal and mucosal sides.
      GLcNBu was measured using HPLC. RESULT: Following i.v. administration, the
      terminal half-life was 0.29 -/+ 0.06 h, volume of distribution at steady state
      was 2.1 -/+ 0.26 L/kg and total body clearance was 5.23 -/+ 1.44 L/h/kg.
      Bioavailability was less than 17% and 100% following oral and i.p. doses
      respectively. GLcNBu was rapidly absorbed after oral doses (Tmax, 29-40 min).
      Food had no significant effect on the pharmacokinetics of GLcNBu. There was no
      evidence of breakdown of GLcNBu in the presence of everted intestine. The mucosal
      to serosal transport of GLcNBu was about 20% after 2 h incubation. CONCLUSION:
      GLcNBu has rapid but low absorption and is widely distributed and efficiently
      cleared. The gut rather than liver is mainly responsible for the low
      bioavailability of GLcNBu. Limited absorption of GLcNBu suggests a transport
      dependent absorption. Food does not significantly affect the bioavailability of
      GLcNBu.

PMID- 17207419
TI  - Atorvastatin attenuating down-regulation of peroxisome proliferator-activated
      receptor gamma in preventing cardiac hypertrophy of rats in vitro and in vivo.
AB  - PURPOSE: To investigate whether the role of atorvastatin in suppression of
      cardiac hypertrophy is potentially associated with the change of peroxisome
      proliferator-activated receptor gamma (PPARgamma) expression, and the anti
      inflammatory effect in vitro and in vivo. METHOD: Cardiac hypertrophy was
      established by angiotensin II in neonatal cardiac myocytes in vitro and
      incomplete ligation of abdominal aorta of SD rats in vivo. PPARgamma and
      cytokines mRNA expression was evaluated by RT-PCR, and the rate of protein
      synthesis in cardiac myocytes by 3H-leucine incorporation. RESULTS: Atorvastatin
      attenuated downregulation of PPARgamma mRNA and inhibited brain natriuretic
      peptide (BNP), interleukin-1beta (IL-1beta) and matrix metalloproteinase 9 (MMP9)
      mRNA expression, as well as 3H-leucine incorporation in a dose-dependent manner
      in vitro. Furthermore, atorvastatin reduced the mRNA expression of BNP, IL-1beta
      and MMP9, and enhanced PPARgamma mRNA expression, and diminished the pressure
      overload-induced increase in the ratio of heart weight to body weight, left
      ventricular wall thickness and myocyte diameter of rats in vivo. CONCLUSION:
      Atorvastatin prevents cardiac hypertrophy of rats, probably associated with the
      modulation of PPARgamma and the inhibition of myocardial inflammation.
      Atorvastatin may play a role in prevention and treatment of cardiovascular
      diseases characterized by cardiac hypertrophy.

PMID- 17207420
TI  - The merits of a robot: a Dutch experience.
AB  - PURPOSE: To determine the merits of a robot at the community pharmacy in a quasi
      experiment. METHOD: The applied methods for data-collection were barcode-time
      measurements, direct observations, time-interval studies, and tally at a Dutch
      community pharmacy. The topics consisted of workload, waiting times, congestion,
      slack, general work, counter work, and work at the consultation room. The topics
      were studied in pre-test and post-test stages, each stage during six weeks. By
      using these topics and some additional data from the pharmacy, the economics of
      the robot were also assessed. RESULTS: The workload decreased with 15
      prescriptions per person per day. The waiting times decreased with one minute and
      18 seconds per dispensing process, reducing the wait until counter contact. The
      day congestion decreased with one hour 27 minutes and 36 seconds, and the day
      slack increased with 28 minutes. The analysis of the general work showed no
      appreciable difference in the bulk of the care-related activities and the other
      activities. However, some work was re-shuffled: 7% increase at counter work and
      7% decrease at logistics. Moreover, statistically significant increases were
      observed at counter work (5%) and robot work (4%), and significant decreases at
      telephone (3%) and filling work in presence of the patient (4%). The counter
      tally study showed a rise in care-related activities with 8%. Moreover, it also
      illuminated a statistically significant decrease at no information (11%) and an
      increase at only social (2%). The consultation room was never used during the
      study. The pharmacy economics of the robot showed that the robot had high
      estimated costs for purchase, depreciation, and maintenance: EUR 187,024 in the
      first year. Moreover, the robot had positive impact on waiting times, congestion,
      staffing, logistics, and care-related work, which was estimated on EUR 91,198 in
      the first year. The estimated payback time of the robot was three years.
      CONCLUSIONS: An introduction of the robot may indeed have the often supposed
      positive effects on pharmaceutical care. Even though the costs are high and the
      technical problems are present, the robot seems to be financial beneficial after
      three years. The robot can create space for pharmaceutical care, but it has a
      substantial cost.

PMID- 17207421
TI  - Endoglin expression in hyper-cholesterolemia and after atorvastatin treatment in
      apoE-deficient mice.
AB  - PURPOSE: Endoglin (CD105) is a marker of activated endothelium and a modulator of
      TGF-beta signaling. We hypothesized whether endothelial expression of endoglin is
      changed in hypercholesterolemia as well as whether its expression is affected by
      atorvastatin treatment in apoE-deficient mice. METHODS: ApoE-deficient mice were
      fed with the chow diet for either 4 weeks or for 12 weeks respectively. In two
      treated groups, mice were fed with chow diet except atorvastatin was added to the
      diet for the last 4 weeks or for the last 8 weeks respectively, before
      euthanasia. RESULTS: Administration of atorvastatin did not affect lipid
      parameters after 4 weeks treatment, however increased all lipid parameters after
      8 weeks of treatment. Stereological analysis of immunohistochemical staining
      revealed that atorvastatin significantly decreased endoglin expression in
      endothelium after 4 weeks of treatment but increased it after 8 weeks of
      treatment. CONCLUSIONS: This study demonstrates that endoglin is expressed by
      aortic endothelium showing similar staining patterns like other markers involved
      in the process of atherosclerosis. In addition, we showed that endoglin
      expression in endothelium could be affected by the administration of atorvastatin
      beyond its lipid lowering effects in apoE-deficient mice.

PMID- 17207422
TI  - Stability considerations in liquid dosage forms extemporaneously prepared from
      commercially available products.
AB  - The pharmacist, both in community and hospital pharmacy practice, is often
      challenged with the preparation of a liquid dosage form not available
      commercially for paediatric patients, those adults unable to swallow tablets or
      capsules and patients who must receive medications via nasogastric or gastrostomy
      tubes. Recognising the lack of information available to healthcare professionals,
      a general discussion of the various parameters that may be modified in preparing
      these dosage forms and a tabulated summary of the dosage forms presented in the
      literature is described, which, although not exhaustive, will provide information
      on the formulation and stability of the most commonly prepared extemporaneous
      liquid dosage forms. An extensive survey of the literature and investigation of
      83 liquid dosage forms revealed that stability considerations were of concern for
      only 7.2% of these liquid dosage forms, extemporaneously prepared from the
      following commercially available products: captopril, hydralazine hydrochloride,
      isoniazid, levothyroxine sodium, phenoxybenzamine hydrochloride and tetracycline
      hydrochloride. Inclusion of the antioxidant, sodium ascorbate in the liquid
      dosage form for captopril resulted in improved stability at 4 degrees C.
      Hydralazine hydrochloride, isoniazid and phenoxybenzamine hydrochloride were
      adversely affected due to interactions with excipients in the formulation, while
      the effect of the preservative in lowering the pH in a levothyroxine sodium
      mixture resulted in decreased stability. Interestingly, the instability in these
      formulations is primarily due to interactions between the drug substance and the
      excipients rather than degradation of the active pharmaceutical ingredient by
      standard routes such as oxidation, hydrolysis, photolysis or thermolysis. This
      low percentage however illustrates the low risk associated with these dosage
      forms investigated. It may be concluded that when considering the safety and
      efficacy of liquid dosage forms prepared extemporaneously, it is thus important
      to consider not only the stability of the drug substance but the entire
      formulation.

PMID- 17207423
TI  - Prevalence of potential drug-drug interactions and its associated factors in a
      Brazilian teaching hospital.
AB  - PURPOSE: The hazards of prescribing many drugs, including side-effects, drug-drug
      interactions (DDI) and difficulties of compliance have long been recognized as
      particular problems when prescribing. This study estimates the rate and factors
      associated with potential DDI in prescriptions from wards of a Brazilian teaching
      hospital. METHODS: Data were retrieved from wards of a teaching hospital (300
      beds) handwritten prescription, once a week during a period of 4 months in 2004.
      Potential DDI were identified using DrugReax system. Patient's age and gender,
      number of prescribers; number of drugs and therapeutic drug classes on
      prescriptions were explored as associated factors to DDI. RESULTS: The overall
      frequency of potential DDI was 49.7%. The frequency of the potentially major DDI
      was 3.4%, with digoxin-hydrochlorothiazide as the most common interacting pair.
      The rate of potential DDI was significantly associated to in-patients' gender
      [woman, Odds ratio (OR)=1.23 (P=0.035)], age=55 years old [OR=1.5 (P=0.0008)],
      number of therapeutic drug class (ATC code, level 1)=4 [OR=5.5 (P=0.0000),
      cardiology patients [OR=7.87 (P=0.0000)] hospitalized at weekends [OR=1.24
      (P=0.039)] and having digoxin prescribed [OR=16.79 (P=0.0000)]. A positive
      correlation was found between DDI, patient's age, number of drugs and therapeutic
      action ATC codes were significant, controlling for gender (Pearson's r=0.628,
      P=0.001). CONCLUSIONS: Cardiology women inpatients, age more then 55 years old, 7
      or more drugs prescribed (including digoxin) and hospitalized at weekends should
      be closely monitored for adverse outcomes from DDI. A collaborative approach
      toward drug selection is strongly recommended, as well as electronic prescribing
      and development of pharmaceutical care in Brazilian hospitals.

PMID- 17207424
TI  - The ethics of care.

PMID- 17207425
TI  - Reliability and validity of the American Orthopaedic Foot and Ankle Society
      Clinical Rating Scale: a pilot study for the hallux and lesser toes.
AB  - BACKGROUND: The use of clinical outcomes instruments is essential for the
      effective interpretation of individual patient progress as well as the comparison
      of treatment groups. An outcomes instrument must be reliable and valid to obtain
      any meaningful data. The purpose of the present study was to examine the
      reliability and validity of the American Orthopaedic Foot and Ankle Society
      (AOFAS) clinical rating scale for the hallux metatarsophalangeal-interphalangeal
      and lesser toes metatarsophalangeal-interphalangeal joints. METHODS: Eleven
      patients (one man, 10 women) with an average age of 54 (range 40 to 72) years and
      with classic rheumatoid arthritis not currently treated for foot complaints were
      enrolled in the present study. The average duration of rheumatoid arthritis was
      14 years. Each patient completed a set of two outcomes instruments and had a
      physical examination by a single clinician at the initial visit and returned at 1
      week for completion of the same scales and examination. The outcomes scales used
      were the AOFAS clinical rating scale for the hallux, the AOFAS clinical rating
      scale for the lesser toes, and the previously validated Foot Function Index
      (FFI). Test-retest reliability was evaluated using intraclass correlation
      coefficients between week 1 and week 2 for the summary scores as well as for the
      subscales of pain and activity. Consistency between the two instruments was
      evaluated with Pearson correlation coefficients. RESULTS: The AOFAS clinical
      rating scale for the hallux and lesser toes is repeatable between 1-week trials
      (ICC 0.95; p < 0.05; ICC 0.80; p < 0.05, respectively). Moderately strong
      correlations were found between the mean values for the AOFAS hallux and FFI (r =
      -0.81; p < 0.05). Weaker correlations were seen between the mean values for the
      AOFAS lesser toes and FFI scales (r = -0.69; p < 0.05). CONCLUSIONS: The hallux
      subscale for pain correlates strongly with the FFI subscale for pain, suggesting
      high content validity (r = -0.94; p < 0.001). Ceiling effects were seen with the
      AOFAS lesser toe subscale for activity, limiting its usefulness in a general
      patient population. The AOFAS lesser toe subscale for pain and the AOFAS hallux
      subscale for activity correlated weakly with the FFI values (r = -0.31; r = 
      0.37; p > 0.05, respectively). CONCLUSIONS: Although the AOFAS hallux and lesser
      toe scales were found to be reliable in a rheumatoid patient population, their
      validity remains in question. These findings must be confirmed with larger
      subject numbers, with the inclusion of symptomatic patients before recommended
      routine use of the hallux clinical rating and lesser toe clinical rating scales.

PMID- 17207426
TI  - Results of step-cut medial malleolar osteotomy.
AB  - BACKGROUND: Treatment of certain complex ankle pathology, such as a talar body
      fracture or osteochondral lesion requiring grafting, can necessitate medial
      malleolar osteotomy for adequate operative exposure. This paper evaluates the
      step-cut medial malleolar osteotomy for exposure of the ankle joint. METHOD:
      Fourteen patients with intra-articular pathology, including talar body fractures
      or osteochondral lesions necessitating extensive intra-articular exposure had
      step-cut malleolar osteotomy. The average age of the patients was 37 (range 20
      90) years, and the average followup was 8 months. RESULTS: All 14 patients had an
      uncomplicated intraoperative course, with excellent exposure of the ankle joint.
      All patients had prompt healing of the osteotomy by 6 weeks after surgery without
      loss of reduction. None of the patients had pain at the osteotomy site.
      CONCLUSIONS: Step-cut medial malleolar osteotomy is an excellent, reproducible
      method for extensive exposure of the talar dome.

PMID- 17207427
TI  - Surgical treatment of severe hallux valgus: the state of practice among academic
      foot and ankle surgeons.
AB  - BACKGROUND: The purpose of this study was to evaluate the operative procedures
      used for treatment of severe hallux valgus by academic foot and ankle surgeons
      practicing in the United States. METHODS: A patient with severe hallux valgus
      deformity was developed as a hypothetical case: a 50-year-old woman with a severe
      deformity (intermetatarsal angle = 20 degrees; hallux valgus angle = 42 degrees).
      The patient was symptomatic with pain, did not improve with conservative
      measures, and wanted the deformity corrected. This case was sent to academic foot
      and ankle surgeons in a survey to determine their preferred operative treatment
      for this case. The overall response rate was 84% (128 of 153). To be included in
      the study group each surgeon had to have 1) foot and ankle patients comprising
      50% or more of his clinical practice and 2) direct responsibility for teaching
      orthopaedic residents. One hundred and five respondents met the inclusion
      criteria and formed the study group; however, three surveys with invalid
      responses were deleted. RESULTS: Fifty-two percent (54 of 102) of the respondents
      chose a metatarsal osteotomy, 26% (26 of 102) a first metatarsophalangeal (MTP)
      joint arthrodesis, and 24% (24 of 102) a Lapidus procedure. Two respondents chose
      both an arthrodesis and a metatarsal osteotomy. Among the 54 respondents who
      chose metatarsal osteotomies, 24 used a Ludloff, 16 a proximal crescentic, eight
      a proximal chevron, two a scarf, two a distal chevron, and two other. In
      addition, secondary procedures to enhance the correction included a Weil
      osteotomy in 46% (47 of 102) and an Akin osteotomy in 30% (31 of 102).
      CONCLUSIONS: There was a wide variation in the type of procedure used to correct
      this severe hallux valgus deformity; approximately 50% of the respondents chose a
      metatarsal osteotomy, 25% chose a first MTP joint arthrodesis, and 25% a Lapidus
      procedure.

PMID- 17207428
TI  - Medial deviation of the first metatarsal in incipient hallux valgus deformity.
AB  - BACKGROUND: The aim of this study was to determine whether excessive medial
      deviation of the first metatarsal (excessive intermetatarsal angle) is present in
      the initial phase of hallux valgus. METHODS: The intermetatarsal angle between
      the first and second metatarsals (1-2 IMA) was radiographically studied in 49
      normal feet and in 49 feet with mild hallux valgus deformity. RESULTS: The
      results demonstrated a statistically significant difference in the mean
      intermetatarsal angle between the two groups (8.76 degrees in normal feet; 9.98
      degrees in affected feet). However, we believe that is not clinically
      significant. Other authors, comparing the 1-2 IMA in patients with or without
      more advanced hallux valgus, reported greater differences than those obtained in
      this study. CONCLUSIONS: Excessive medial deviation of the first metatarsal is
      not a causal factor but rather a consequence of hallux valgus deformity.

PMID- 17207429
TI  - Variation of the distal metatarsal articular angle with axial rotation and
      inclination of the first metatarsal.
AB  - BACKGROUND: The distal metatarsal articular angle (DMAA) is a radiographic
      measure of the orientation of the first metatarsal articular surface. There is
      debate with regards to the accuracy, reproducibility, and validity of measurement
      of the DMAA in the literature. This study aimed to test the validity of the
      measurement of the DMAA from standard radiographs, to explore the trigonometric
      relationship of the first metatarsal rotation and the DMAA, and to assess
      interobserver reliability. METHODS: Thirty-four separate dry cadaver first
      metatarsal bones were mounted onto a customized light-box-protractor, allowing
      controlled incremental changes in rotation and inclination. A series of 39
      digital photographs were taken of each metatarsal in 5-degree increments of
      rotation between 30 degrees supination and 30 degrees pronation at 10, 20 and 30
      degrees of inclination. Three reviewers performed blinded DMAA measurements from
      each photographic image; the data were collated for statistical analysis. The
      data were analysed using a mixed effects linear model comparing the DMAA with
      rotation of the first metatarsal. RESULTS: A strong statistically significant
      trend of increasing score with increasing pronation of the metatarsal was
      observed, the relationship was approximately linear. There was a strong effect of
      inclination, but the strength of this varied with rotation and was amplified at
      higher inclinations. Interobserver error was noted in line with other studies,
      but even allowing for this interobserver error, the linear relationship was
      maintained. CONCLUSIONS: This study showed that the DMAA varies significantly in
      a linear pattern with axial rotation of the first metatarsal. Inclination of the
      first metatarsal also affects the magnitude of the angle. This study does not
      refute the DMAA as an entity but does confirm the inaccuracy of extrapolating the
      DMAA from plain anteroposterior radiographs.

PMID- 17207430
TI  - First metatarsal bone: an anatomic study.
AB  - BACKGROUND: The purpose of this study was to establish the range of anatomic
      variations of the first metatarsal bone, including both the angulations of the
      articular surfaces and the dimensions of the bone in a large sample. METHODS:
      Four hundred and seventy-eight first metatarsal bones of 239 cadaver specimens
      were studied. The following parameters were recorded: the distal metatarsal
      articular angle (DMAA), distal metatarsal articular surface shape, proximal
      metatarsal articular angle (PMAA), the first metatarsal bone length and width at
      the mid-region of the shaft, and the existence of a joint between the bases of
      the first and second metatarsals. These parameters were correlated to the
      specimen's age, sex, race, height, and weight. The DMAA and PMAA were measured
      from a digital picture of the first metatarsal bone by a specially designed
      computer analysis program. RESULTS: Males and African-American race had a longer
      and wider metatarsal. The joint between the first and second bases was present in
      25% of the population. The DMAA ranged from -14 degrees of medial deviation to 30
      degrees of lateral deviation with an overall average of 8.21 degrees. The DMAA
      increased 1 to 3 degrees with every 10 years in age for both right and left bones
      with a p value of < 0.01 and < 0.001, respectively, and the average increase from
      20 to 60 years of age was 4.5 degrees. The PMAA ranged from -13.8 degrees of
      lateral deviation to 12.7 degrees of medial deviation with an overall average of 
      1 degrees. PMAA significantly deviated laterally in the presence of a joint
      between the bases of the first and second metatarsals (p < 0.001). The male and
      female means for the DMAA and PMAA were nearly equal. CONCLUSIONS: The DMAA had a
      wider range than reported in the literature, and it increased with age. The first
      second metatarsal joint was accompanied by lateral deviation of the PMAA.
      CLINICAL RELEVANCE: Laterally deviated PMAA could predispose to a varus deformity
      of the first metatarsal.

PMID- 17207431
TI  - Indications for and technique of first metatarsophalangeal joint arthroscopy.
AB  - BACKGROUND: Arthroscopy of the great toe metatarsophalangeal joint has been used
      for a variety of indications, ranging from synovitis to osteochondral defects.
      The purpose of the present study was to define the indications for arthroscopy,
      assess its efficacy, and demonstrate the limitations of this procedure. METHODS:
      Hallux metatarsophalangeal joint arthroscopy was used in 20 patients (25 feet).
      Indications included degenerative disease with early osteophytosis,
      chondromalacia, osteochondral defects, loose bodies, arthrofibrosis, synovitis,
      gouty arthritis, first metatarsophalangeal joint pain with no obvious findings
      clinically and radiographically in young adults, and intra-articular fracture of
      the first metatarsophalangeal joint. All patients had a minimal followup of 2
      years and were evaluated clinically and radiographically. RESULTS: Arthroscopic
      surgery resulted in pain free first metatarsophalangeal joints in 95% (19 of 20
      patients). Patients with degenerative disease had a pain-free joint for a minimum
      of 2 years. The patients with gouty arthritis and intra-articular fracture had
      good functional outcomes. Arthroscopy also helped in identifying the pathology in
      painful joints with no obvious radiographic features that included conditions
      such as 'meniscoid' and other impingement lesions. CONCLUSION: Arthroscopy of the
      first metatarsophalangeal joint is not suitable for patients with extensive
      degenerative changes and large osteophytes and those that require cheilectomy or
      arthrodesis. Arthroscopic management of certain painful hallucal
      metatarsophalangeal joints is a specialized technique, which if performed for the
      right indications, gives a favorable outcome with minimal complications.

PMID- 17207432
TI  - Positive hindfoot valgus and osteoarthritis of the first metatarsophalangeal
      joint.
AB  - BACKGROUND: The aim of this retrospective cohort study was to evaluate the
      association between increased hindfoot valgus and the subsequent development of
      osteoarthritis of the first metatarsophalangeal (MTP) joint. Specifically, our
      hypothesis was that among individuals free from first MTP joint osteoarthritis,
      those who have positive hindfoot valgus are more likely to develop first MTP
      joint osteoarthritis than are those individuals with normal hindfoot alignment.
      METHODS: Our sample consisted of 1592 men and women, 40 years of age or older,
      participating in the Clearwater Osteoarthritis Study (1988 to 2001). Biennial
      physical examinations, including serial radiographs, were conducted. The Kellgren
      and Lawrence ordinal scale was used to determine radiographic evidence (grades
      2+) of the study outcomes and incidence of first MTP joint osteoarthritis.
      Standing hindfoot valgus was assessed visually by a registered nurse, with a
      hindfoot valgus measurement of more than 5 degrees classified as a positive
      hindfoot valgus. RESULTS: Individuals with hindfoot valgus were 23% more likely
      to subsequently develop first MTP joint osteoarthritis than were those without
      hindfoot malalignment (risk ratio = 1.23; p-value < 0.006). This risk estimate
      reflects the potential influence of age, gender, and body mass index.
      CONCLUSIONS: Our data suggest that hindfoot valgus may increase the risk of
      developing foot osteoarthritis. The association of hindfoot valgus with first MTP
      joint osteoarthritis in this epidemiological assessment is supportive of the
      mechanical theory for the development of osteoarthritis. The authors speculate
      that future, related studies may determine that osteoarthritis prevention
      strategies can be broadened to include individuals with positive hindfoot valgus.

PMID- 17207433
TI  - Incidence of foot and ankle injuries in West Point cadets with pes planus
      compared to the general cadet population.
AB  - BACKGROUND: The relationship between pes planus and injuries of the lower
      extremity is controversial. However, few studies have used standardized means of
      evaluating and defining pes planus, and none have had a controlled patient
      population. The objective of this study was to evaluate an ideal population of
      physically active individuals to establish a potential correlation between pes
      planus, as defined by a standardized method, and injuries to the lower extremity.
      METHODS: A standardized technique for evaluating arch height, based on a midfoot
      ratio established by Harris mat print calculations, was used to assess a
      consecutive series of 512 newly entered West Point cadets. Pes planus was defined
      as more than 2 standard deviations above the mean midfoot ratio of the
      population. After 46 months, a retrospective chart review was done to identify
      lower extremity injuries sustained in this group of young healthy patients. The
      results of the footprint analysis were correlated with the medical record
      findings. RESULTS: Thirty-three cadets were found to have pes planus; 13 had only
      left foot involvement, 15 had right foot only involvement, and five had bilateral
      pes planus. There were no cavus feet. Statistically significant relationships
      were seen between the degree of pes planus and total number of injuries sustained
      (p = 0.007), the overall size of the foot and total number of injuries (p =
      0.041), left flat feet and left midfoot injuries (p = 0.028), left pes planus and
      right midfoot injuries (p = 0.008), left pes planus and left knee injuries (p =
      0.038), and right pes planus and right knee injuries (p = 0.027). Women had
      smaller feet (p = 0.000), smaller midfoot ratios (right, p = 0.013; left p =
      0.003), yet they had an increased number of injuries (Pearson's coefficient 
      0.119; p = 0.007). CONCLUSIONS: The current study found significant relationships
      between pes planus and number of injuries sustained over a 4-year period at West
      Point. While women were found to have smaller feet and lesser degrees of pes
      planus, they sustained more injuries than men.

PMID- 17207434
TI  - Diabetic foot complications in a northern Canadian Aboriginal community.
AB  - BACKGROUND: Limited access to basic foot care and protective footwear may
      contribute to diabetic foot complications. The purpose of this study was to
      determine the prevalence of foot complications, ongoing foot care, and footwear
      use in diabetic subjects in a remote northern Canadian Aboriginal community.
      METHODS: This was a cross-sectional cohort study of 169 diabetic people,
      including interview, physical examination, and retrospective chart review.
      RESULTS: The mean age of the 169 diabetic individuals in the study was 56 +/- 12
      years and their duration of diabetes 10 +/- 7 years. There were 139 (82%)
      individuals who had 418 diabetic foot complications (average, 3.0 complications
      per subject with complications), including toenail pathology, foot and ankle
      deformities, calluses, impaired pulses, neuropathy, past or present ulcer,
      amputation, and Charcot arthropathy. Risk classification showed that 69 (41%)
      individuals were at risk for future ulceration. Fifty-five (33%) individuals had
      inadequate footwear for their foot risk category, and only 11 (17%) of 66
      individuals in the higher risk categories (categories 2 and 3) had suitable
      footwear. In a 7-year period, only 0.7 screening foot examinations per diabetic
      subject per year were documented. However, during this period, foot problems
      accounted for 498 (18%) local emergency room visits, 359 (16%) hospitalization
      days, 109 (11%) nonemergency transfers, and 4 (6%) emergency transfers to a
      tertiary care hospital. CONCLUSIONS: Foot and ankle complications of diabetes in
      this remote Aboriginal community were common and associated with substantial
      morbidity. Preventive diabetic foot screening examinations and footwear were
      inadequate. The results suggest that programs for prevention and early detection
      of complications are needed, including foot screening, provision of appropriate
      footwear, and foot care.

PMID- 17207435
TI  - Superior retinaculoplasty for recurrent dislocation of peroneal tendons.
AB  - BACKGROUND: Although dislocation of peroneal tendons is an uncommon injury, if it
      does occur, daily and sports activities may be restricted because of snapping of
      the tendons and pain in the posterolateral aspect of the ankle joint. Many
      operative procedures have been reported for this pathology, including anatomic
      reattachment of the retinaculum, bone block procedures, tissue-transfer
      procedures, and groove-deepening. However, no procedure has been established as
      the "gold standard." Successful results were reported after anatomic reattachment
      of the detached superior peroneal retinaculum and periosteum of the fibula. We
      have modified the procedure to reduce operative invasiveness and introduced a
      method to determine proper tension when suturing the retinaculum to the fibula.
      METHODS: In our retinaculoplasty, the false pouch was opened through one
      incision, and the retinaculum was sutured to the fibula while measuring the
      tension, avoiding too tight or too loose suturing. We performed this procedure in
      20 patients with symptomatic dislocation of peroneal tendons in whom conservative
      treatment had failed. We followed them over 2 years, and clinical results were
      evaluated. RESULTS: No patient had re-dislocation of the peroneal tendons during
      the followup period. Fifteen of 18 patients who had been involved in sports
      activities returned to their previous activities without reducing their activity
      levels. All patients acquired full range of motion of the ankle joint
      postoperatively. The preoperative American Orthopaedic Foot and Ankle Society
      (AOFAS) scores improved significantly (p value < 0.01) postoperatively.
      CONCLUSIONS: This study demonstrated that the described repair successfully
      treated patients with symptomatic dislocation of the peroneal tendon and should
      be considered for this pathology.

PMID- 17207436
TI  - Arthroscopic ankle arthrodesis: factors influencing union in 39 consecutive
      patients.
AB  - BACKGROUND: Arthroscopic ankle arthrodesis is an effective alternative to open
      techniques with established advantages in select patient populations. The purpose
      of this study was to evaluate patients who had arthroscopic ankle arthrodesis for
      end-stage arthritis with minimal to no deformity of the ankle and to report
      factors influencing union. METHODS: Thirty-nine consecutive patients had
      arthroscopic ankle arthrodesis between 1994 and 2003. Clinical records and
      radiographs were retrospectively reviewed to evaluate variables that could
      predispose patients to nonunion. Union outcomes were correlated with etiology of
      arthritis, ankle deformity, medical co-morbidities, and the use of demineralized
      bone matrix or platelet-rich plasma. Arthroscopic ankle arthrodesis was
      accomplished with a consistent technique using crossed transmalleolar cannulated
      screw fixation. RESULTS: Thirty-four of 39 patients (87.2%) achieved radiographic
      and clinical union. The average time to fusion was 47 (range 37 to 70) days. Poor
      bone quality and inherent positional ankle deformity were identified as risk
      factors for nonunion. Patients who smoked, had diabetes mellitus, peripheral
      neuropathy, or other medical co-morbidities attained ankle union in nearly all
      cases. In obese patients, there was an observed trend towards ankle nonunion
      (relative risk 5.81, p = 0.049, Fisher's Exact test). The addition of
      demineralized bone matrix or platelet-rich plasma did not improve the rate of
      ankle union. Aside from nonunion, 10 patients developed minor complications.
      CONCLUSION: Arthroscopic ankle arthrodesis achieves high union rates, facilitates
      short time to union, and permits rapid patient mobility. Careful patient
      selection is important for the procedure. Synthetic allograft or platelet-rich
      plasma did not enhance the fusion rate. Obese patients showed a trend towards
      nonunion in this series.

PMID- 17207437
TI  - Stretching for prevention of Achilles tendon injuries: a review of the
      literature.
AB  - Professional and recreational athletes commonly perform pre-exercise stretching
      to prevent musculoskeletal injuries. Little definitive evidence exists that
      clearly demonstrates the efficacy of stretching in reducing injury. Achilles
      tendon injuries are among the most common injuries affecting active individuals
      in the United States today. Clinicians commonly recommend stretching the Achilles
      tendon without concrete scientific evidence to support such a claim. Few studies
      have addressed the effect of stretching in Achilles tendon injuries, and it is
      unclear if the conclusions made for musculoskeletal injuries can be applied to
      the Achilles tendon. Biomechanical studies of the Achilles tendon and
      measurements of the tendon's reflex activity have demonstrated possible
      mechanisms for the potential benefit of stretching, including load-induced
      hypertrophy and increased tendon tensile strength. Recent prospective studies
      have contended that reductions in plantarflexor strength and increases in ankle
      dorsiflexion range of motion from stretching the Achilles tendon may increase the
      risk of injury. Studies examining stretching in injury prevention, the
      biomechanical properties of injuries to the Achilles tendon were compiled and
      reviewed. Although many theories have been published regarding the potential
      benefits and limitations of stretching, few studies have been able to
      definitively demonstrate its utility in injury prevention.

PMID- 17207438
TI  - Detection of orthopaedic foot and ankle implants by security screening devices.
AB  - BACKGROUND: A common question asked by patients contemplating foot and ankle
      surgery is whether the implants used will set off security screening devices in
      airports and elsewhere. Detectability of specific implants may require the
      orthopaedic surgeon to provide attestation regarding their presence in patients
      undergoing implantation of these devices. Only two studies have been published
      since security measures became more stringent in the post-9/11 era. None of these
      studies specifically focused on the large numbers of orthopaedic foot and ankle
      implants in use today. This study establishes empiric data on the detectability
      by security screening devices of some currently used foot and ankle implants.
      METHODS: A list of foot and ankle procedures was compiled, including procedures
      frequently used by general orthopaedists as well as those usually performed only
      by foot and ankle specialists. Implants tested included those used for open
      reduction and internal fixation, joint fusion, joint arthroplasty, osteotomies,
      arthroreisis, and internal bone stimulation. A test subject walked through a gate
      type security device and was subsequently screened using a wand-type detection
      device while wearing each construct grouping. The screening was repeated with the
      implants placed within uncooked steak to simulate subcutaneous and submuscular
      implantation. RESULTS: None of the implants were detected by the gate-type
      security device. Specific implants that triggered the wand-type detection device
      regardless of coverage with the meat were total ankle prostheses, implantable
      bone stimulators, large metatarsophalangeal hemiarthroplasty, large arthroreisis
      plugs, medial distal tibial locking construct, supramalleolar osteotomy fixation,
      stainless steel bimalleolar ankle fracture fixation, calcaneal fracture plate and
      screw constructs, large fragment blade plate constructs, intramedullary
      tibiotalocalcaneal fusion constructs, and screw fixation for calcaneal
      osteotomies, ankle arthrodeses, triple arthrodeses, and stainless steel first
      metatarsophalangeal joint arthrodeses. The placement of implants in meat
      prevented the detectability of only the stainless steel Jones fracture implant
      (stainless steel 6.5-mm cannulated screw) and the stainless steel midfoot fusion
      construct (four stainless steel 4.0-mm cannulated screws). CONCLUSIONS: These
      data may help the orthopaedic surgeon in counseling patients as to the
      detectability of some orthopaedic foot and ankle implants in use today. Specific
      constructs for which documentation may need to be provided to the patient are
      identified. As security standards evolve and the environments in which they are
      practiced change, empiric testing of many of these devices may need to be
      repeated.

PMID- 17207439
TI  - Plantarflexion strength of the toes: age and gender differences and evaluation of
      a clinical screening test.
AB  - BACKGROUND: The toes play an important stabilizing role in weightbearing
      activities. However, the factors that influence toe plantarflexion strength are
      poorly understood, and there are no validated measures for assessing toe weakness
      in the clinical setting. Therefore, the objectives of this study were to
      determine whether plantarflexion strength of the toes differs according to age
      and gender and to evaluate the validity of a clinical screening test for
      assessing toe plantarflexor weakness (the paper grip test). METHODS:
      Plantarflexion strength of the hallux and lesser toes was measured in 40 young
      participants (20 men and 20 women, mean age 20.8 +/- 2.2 years) and 40 older
      participants (20 men and 20 women, mean age 74.6 +/- 5.7 years) using a pressure
      platform in conjunction with clinical assessment using the paper grip test.
      RESULTS: Older participants exhibited 32% less plantarflexion strength of the
      hallux and 27% less plantarflexion strength of the lesser toes compared to
      younger participants, and women exhibited 42% less hallux plantarflexor strength
      than men. Gender did not influence lesser toe plantarflexor strength.
      Participants who failed the paper grip test exhibited significantly reduced
      plantarflexion strength for both the hallux and lesser toes. The sensitivity and
      specificity of the paper grip test of the hallux to predict plantarflexor
      strength less than 2.6 kg was 80% and 79%, respectively, and the sensitivity and
      specificity of the paper grip test of the lesser toes to predict plantarflexor
      strength less than 2.2 kg was 75% and 74%, respectively. CONCLUSIONS: These
      findings indicate that aging is associated with reduced plantarflexion strength
      of the toes. The paper grip test may be a useful screening tool to detect toe
      weakness in the clinical setting.

PMID- 17207440
TI  - Radiographic changes and clinical results of osteochondral defects of the talus
      with and without subchondral cysts.
AB  - BACKGROUND: Subchondral cysts are a type of osteochondral defect of the talus and
      can be a source of chronic ankle pain. The treatment modality of this cystic
      lesion is similar to that of other osteochondral defects, but results from
      previous reports are controversial. Therefore, we compared the clinical results
      and radiographic changes in small subchondral talar cystic lesions (less than 1.5
      cm2) to other noncystic defects after arthroscopic operations without bone
      grafting. METHODS: The review covered about 2 years (January, 2001 to April,
      2003) and included 38 patients with an average age of 36.9 years. Followup ranged
      from 24 to 36 months. Arthroscopic microfracture or abrasion arthroplasty was
      performed on 20 defects with subchondral cysts and 18 defects without cysts.
      Clinical results were assessed by the ankle-hindfoot scale of the American
      Orthopaedic Foot and Ankle Society (AOFAS); radiographic changes were assessed by
      the transverse long diameter and the area (mm2) of the cyst on digital
      radiographs using a PACS (Picture Archiving Communication System). RESULTS: At
      the last followup, AOFAS clinical scores improved similarly in cystic and
      noncystic defects. The average diameter of the cysts decreased from 8 +/- 2 mm to
      6 +/- 2 mm (p < 0.01). The area attributed to the cyst also decreased, from 49 +/
      17 mm2 (24 to 84 mm2) to 23 +/- 8 mm2 (4 to 34 mm2) (p < 0.01). There were no
      differences in the clinical results between the cystic and noncystic defects.
      CONCLUSIONS: Good clinical and radiographic results were obtained after
      arthroscopic treatment of osteochondral defects with a small subchondral cyst.
      Our results suggest that a small cystic lesion can be treated by arthroscopic
      microfracture or abrasion arthroplasty and that the existence of a small cyst in
      an osteochondral defect lesion may not affect the postoperative prognosis.

PMID- 17207441
TI  - Detection of fibular torsional deformities after surgery for ankle fractures with
      a novel CT method.
AB  - BACKGROUND: Substantial fibular torsional deformities were detected after surgery
      for ankle fractures combined with a lesion of the syndesmotic complex using a
      novel CT analyzing method. METHODS: In a prospective study, 61 patients with
      ankle fracture dislocations were treated with trans-syndesmotic screw fixation of
      the distal tibiofibular joint. Postoperative axial CT scans of both lower legs
      under standardized leg positioning conditions were made and analyzed with three
      different methods. Method 1 (M1) used proximal and distal CT planes of the lower
      leg for detection of the fibular torsional angle, method 2 (M2) considered only
      the angle at the distal tibiofibular joint, and method 3 (M3) measured the angles
      between the fibular and tibial tangents at the distal tibiofibular joint. Twenty
      patients with fibular torsional asymmetries of more than 10 degrees were
      evaluated clinically 6 to 34 months postoperatively with the American Orthopaedic
      Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score. RESULTS: Thirty-five of the
      61 patients had torsional side-to-side differences of more than 10 degrees. M1
      and M2 showed statistically significant differences compared to M3 (p = 0.001).
      Validity was controlled by interobserver data, variation coefficients were low
      for M1 and M2. Clinically, six of 20 patients with torsional differences of more
      than 10 degrees had excellent results, while seven had good results and seven had
      moderately functional results. Six of the seven with moderate results had fibular
      torsional differences of more than 15 degrees, two of the seven patients with
      good outcomes. Torsional results of M1 and M2 correlated with the AOFAS score (r
      = -0.506). CONCLUSIONS: Of the 61 ankle fractures with ruptures of the
      syndesmotic complex, 25% showed torsional side-to-side differences of more than
      10 degrees on proximal and distal CT planes. This CT technique correlated with
      the AOFAS score and could help determine when early operative revision is
      indicated.

PMID- 17207442
TI  - The single medial approach to triple arthrodesis: a cadaver study.
AB  - BACKGROUND: Triple arthrodesis is traditionally done through a two-incision
      approach. In certain high-risk patients, it may be desirable to do the procedure
      through a single medial incision to avoid lateral wound healing problems. METHOD:
      A cadaver study was undertaken to determine the percentage of surface area of
      each hindfoot joint that could be prepared through a single medial incision. Five
      cadaver legs were assigned to the single-incision group, and one cadaver leg was
      used as the "standard" two-incision specimen. RESULTS: Through the single
      incision approach, 91% of the talonavicular joint, 91% of the subtalar joint, and
      90% of the calcaneocuboid joint could be prepared. These results were comparable
      to the two-incision cadaver specimen results. CONCLUSIONS: A single-incision
      medial approach for triple arthrodesis is a safe and effective technique in the
      management of hindfoot deformity and arthritis in certain high-risk patients.

PMID- 17207443
TI  - Differences in the mechanical properties of calcaneal artificial specimens, fresh
      frozen specimens, and embalmed specimens in experimental testing.
AB  - BACKGROUND: Artificial calcanei, fresh-frozen cadaver specimens, and embalmed
      cadaver specimens were compared in experimental testing under biocompatible
      loading to clarify the biocompatibility of artificial calcaneal specimens for
      implant testing. METHODS: Two different artificial calcaneal bone models
      (Sawbone, Pacific Research Laboratories, Vashon, WA, and Synbone, Synbone Inc.,
      Davos, Switzerland), embalmed cadaver calcaneal specimens (bone density, 313.1 +/
      40.9 g/cm2; age, 43.8 +/- 7.9 years), and fresh-frozen cadaver calcanei (bone
      density, 238.5 +/- 30.0 g/cm2; age, 44.4 +/- 8.2 years) were used for testing.
      Seven specimens of each model or cadaver type were tested. A mechanical testing
      machine (Zwick Inc., Ulm, Germany) was used for loading and measurements. Cyclic
      loading (preload 20 N, load was increased every 100 cycles by 100 N from 1,000 to
      2,500 N, 0.5 mm/s) and load to failure (0.5 mm/s) were performed. The loads were
      applied through an artificial talus in a physiological loading direction. The
      displacement of the posterior facet in the primary loading direction was
      measured. RESULTS: The four different specimen groups showed different stability
      and different displacement in the primary loading direction during cyclic
      loading. The variation of the maximal displacement in the primary loading
      direction for the entire cyclic loading was higher in artificial specimens than
      in the cadaver specimens. CONCLUSIONS: Artificial calcanei (Sawbone, Synbone)
      showed different biomechanical characteristics than cadaver bones (embalmed and
      fresh-frozen) in this experimental setup with biocompatible cyclic loading. These
      results do not support the use of artificial calcanei for biomechanical implant
      testing. Fresh-frozen and embalmed specimens seem to be equally adequate for
      mechanical testing. The low variation of mechanical strength in the unpaired
      cadaver specimens suggests that the use of PAIRED specimens is not necessary.

PMID- 17207444
TI  - Intramedullary nail fixation with posterior-to-anterior compared to transverse
      distal screw placement for tibiotalocalcaneal arthrodesis: a biomechanical
      investigation.
AB  - BACKGROUND: Biomechanical studies on retrograde intramedullary fixation for
      tibiotalocalcaneal fusion have been reported, but no studies have investigated
      dorsiflexion stiffness, load-to-failure, fatigue endurance, and plastic
      deformation using different distal screw orientations. Also, no studies have
      examined the effect of bone density on different distal screw orientations while
      using a fatigue loading mode. METHODS: Eight matched pairs of cadaver legs were
      used. In one leg from each pair an intramedullary nail was inserted with lateral
      to-medial distal screws and in the other with posterior-to-anterior screws. These
      samples underwent dorsiflexion fatigue testing with determination of initial and
      final stiffness, load-to-failure, and degree of plastic deformation at failure.
      DEXA scanning was done of each cadaver specimen to determine bone mineral
      density. Statistical analysis was performed using the Student t-test and a
      Pearson correlation. Significance level was set at p < 0.05. RESULTS: The
      specimens with posterior-to-anterior screws had a significantly higher fatigue
      endurance load-to-failure (1130.0 +/- 362.0 N compared to 801.0 +/- 227 N, p =
      0.01). They also had significantly higher final stiffness (203.1 +/- 23.1 N/mm
      compared to 146.6 +/- 46.2 N/mm, p = 0.05) and lower plastic deformation (2.4 +/-
      1.5 mm compared to 3.8 +/- 2.3 mm, p = 0.04). There was a statistically
      significant correlation between bone mineral density and the difference in
      construct deformation with posterior-to-anterior and lateral-to-medial screw
      orientation (r = 0.76, p = 0.03). CONCLUSIONS: In this biomechanical
      investigation of tibiotalocalcaneal arthrodesis with intramedullary nail
      fixation, posterior-to-anterior distal screw orientation provided more stable
      fixation than lateral-to-medial screw orientation.

PMID- 17207445
TI  - Vascularized bone graft from the medial calcaneus for treatment of large
      osteochondral lesions of the medial talus.
AB  - BACKGROUND: Operative treatment of large osteochondral lesions of the talus is
      difficult because the blood supply is poor in the talar dome. The purpose of this
      study was to evaluate the results of a vascularized bone graft transfer from the
      medial calcaneus to the large osteochondral lesion. METHODS: Four ankles in four
      patients with medial osteochondral lesions were treated through a medial
      transmalleolar approach. Vascularized bone graft was harvested from the medial
      calcaneus using the calcaneal branch of the posterior tibial artery and was
      placed through a fenestration of the medial aspect of the talar dome. The mean
      duration of postoperative followup was 34 (range 24 to 48) months. Clinical and
      radiographic evaluations were made before surgery and at final followup. RESULTS:
      According to the AOFAS ankle-hindfoot scale, mean pain and function scores
      improved from 20 to 33 points and 30 to 43 points, respectively. The mean total
      score improved from 60 to 83 points. Plain radiography at followup showed slight
      osteosclerosis in all patients, but joint space narrowing was not seen in any
      patient. Cysts seen preoperatively on MRI or CT resolved after 12 months
      postoperatively, and MRI or CT did not reveal any findings indicative of
      osteonecrosis. CONCLUSIONS: Clinical and radiographic results were satisfactory.
      Vascularized bone grafts harvested from the calcaneus were successful for the
      treatment of large osteochondral lesions of the medial talus.

PMID- 17207446
TI  - Intraosseous glomus tumor of the ankle: a case report and review of the
      literature.

PMID- 17207447
TI  - Technique tip: Physical examination of the foot and ankle.

PMID- 17207448
TI  - Case report: Nonabsorbable interference screw fixation for tendon transfers in
      the foot and ankle.

PMID- 17207449
TI  - Charcot joint: a complication of open reduction and internal fixation in a
      patient with Guillain-Barre syndrome. A case report.

PMID- 17207450
TI  - Muscle belly tears of the peroneal muscles: a case report.

PMID- 17207451
TI  - Commentary on the clinical diagnosis of Achilles tendon rupture.

PMID- 17207452
TI  - Current concepts review: Tarsal coalition.

PMID- 17207453
TI  - Acetaminophen induces ER dependent signaling in mouse liver.
AB  - Role of endoplasmic reticulum (ER) in liver injury by acetaminophen (AAP) was
      studied in vivo in mice. Sublethal dose of AAP resulted in a decrease in
      microsomal total glutathione and in the reduced-to-total glutathione ratio; redox
      state of thiols of ER resident oxidoreductases ERp72, PDI was shifted towards the
      oxidized form; ER stress-responsive transcription factor ATF6 was activated.
      Transcriptional activation and elevated expression of GADD153/CHOP, an ER stress
      responsive proapoptotic transcription factor, was observed upon AAP addition.
      Transient activation of the ER-resident caspase-12 was shown followed by an
      elevation in procaspase-12 level. Caspase-3 and caspase-8 activation could not be
      detected. AAP treatment resulted in an increased apoptosis of hepatocytes.
      Buthionine-sulfoximine treatment was unable to mimic the effects by AAP
      indicating that glutathione depletion itself is insufficient to provoke
      apoptosis. The results show that intraluminal redox imbalance of the ER and
      consequential activation of signaling processes and proapoptotic events are
      involved in hepatocellular damage caused by AAP overdose.

PMID- 17207454
TI  - Photoinhibition of photosystem II under environmental stress.
AB  - Inhibition of the activity of photosystem II (PSII) under strong light is
      referred to as photoinhibition. This phenomenon is due to an imbalance between
      the rate of photodamage to PSII and the rate of the repair of damaged PSII. In
      the "classical" scheme for the mechanism of photoinhibition, strong light induces
      the production of reactive oxygen species (ROS), which directly inactivate the
      photochemical reaction center of PSII. By contrast, in a new scheme, we propose
      that photodamage is initiated by the direct effect of light on the oxygen
      evolving complex and that ROS inhibit the repair of photodamaged PSII by
      suppressing primarily the synthesis of proteins de novo. The activity of PSII is
      restricted by a variety of environmental stresses. The effects of environmental
      stress on damage to and repair of PSII can be examined separately and it appears
      that environmental stresses, with the exception of strong light, act primarily by
      inhibiting the repair of PSII. Studies have demonstrated that repair-inhibitory
      stresses include CO(2) limitation, moderate heat, high concentrations of NaCl,
      and low temperature, each of which suppresses the synthesis of proteins de novo,
      which is required for the repair of PSII. We postulate that most types of
      environmental stress inhibit the fixation of CO(2) with the resultant generation
      of ROS, which, in turn, inhibit protein synthesis.

PMID- 17207455
TI  - The sensitivity of Photosystem II to damage by UV-B radiation depends on the
      oxidation state of the water-splitting complex.
AB  - The water-oxidizing complex of Photosystem II is an important target of
      ultraviolet-B (280-320 nm) radiation, but the mechanistic background of the UV-B
      induced damage is not well understood. Here we studied the UV-B sensitivity of
      Photosystem II in different oxidation states, called S-states of the water
      oxidizing complex. Photosystem II centers of isolated spinach thylakoids were
      synchronized to different distributions of the S(0), S(1), S(2) and S(3) states
      by using packages of visible light flashes and were exposed to UV-B flashes from
      an excimer laser (lambda=308 nm). The loss of oxygen evolving activity showed
      that the extent of UV-B damage is S-state-dependent. Analysis of the data
      obtained from different synchronizing flash protocols indicated that the UV
      sensitivity of Photosystem II is significantly higher in the S(3) and S(2) states
      than in the S(1) and S(0) states. The data are discussed in terms of a model
      where UV-B-induced inhibition of water oxidation is caused either by direct
      absorption within the catalytic manganese cluster or by damaging intermediates of
      the water oxidation process.

PMID- 17207456
TI  - Effects of topology, length, and charge on the activity of a kininogen-derived
      peptide on lipid membranes and bacteria.
AB  - Effects of topology, length, and charge on peptide interactions with lipid
      bilayers was investigated for variants of the human kininogen-derived peptide
      HKH20 (HKHGHGHGKHKNKGKKNGKH) by ellipsometry, CD, fluorescence spectroscopy, and
      z-potential measurements. The peptides display primarily random coil conformation
      in buffer and at lipid bilayers, and their lipid interaction is dominated by
      electrostatics, the latter evidenced by higher peptide adsorption and resulting
      membrane rupture for an anionic than for a zwitterionic membrane, as well as by
      strongly reduced adsorption and membrane rupture at high ionic strength. At
      sufficiently high peptide charge density, however, electrostatic interactions
      contribute to reducing the peptide adsorption and membrane defect formation.
      Truncating HKH20 into overlapping 10 amino acid peptides resulted in essentially
      eliminated membrane rupture and in a reduced amount peptide charges pinned at the
      lipid bilayer. Finally, cyclic HKH20 was found to be less efficient than the
      linear peptide in causing liposome rupture, partly due to a lower adsorption.
      Analogous results were found regarding bactericidal effects.

PMID- 17207457
TI  - Evaluation of exposure with response-prevention for obsessive compulsive disorder
      in childhood and adolescence.
AB  - The present study was undertaken to estimate the effect of exposure plus response
      prevention (E/RP), delivered alone intensively over 5-weeks and without
      concomitant pharmacotherapy, for children and adolescents with OCD. Twenty
      children and adolescents with OCD, not receiving medication for this condition,
      were randomized to E/RP or a wait-list condition. Statistically and clinically
      significant symptomatic improvement was found in the E/RP group compared with
      controls, with improvement maintained at follow-up an average of 14 weeks later.
      Effect size in the main intention-to-treat analysis was 1.23 and in the secondary
      per protocol analysis was 1.64. This study lends further support to the view that
      E/RP is an effective treatment for childhood OCD.

PMID- 17207458
TI  - A novel anti-WIP monoclonal antibody detects an isoform of WIP that lacks the
      WASP binding domain.
AB  - The majority of Wiskott-Aldrich syndrome protein (WASP) in T cells is in a
      complex with WASP interacting protein (WIP), a 503 a.a. long proline rich
      protein. Here we demonstrate that a novel anti-WIP mAb, 3D10, recognizes an
      epitope in the N-terminal domain of the WIP protein, within the sequence
      13PTFALA18. mAb 3D10 competes with actin, but not with WASP or Nck, for WIP
      binding. Analysis of 3D10 immunoprecipitates failed to demonstrate dissociation
      of the WASP-WIP complex after TCR ligation that we previously reported using a
      polyclonal anti-WIP anti-serum raised against a C-terminal peptide (a.a. 459-503)
      that spanned the WASP binding site. 3D10 mAb allowed the detection of a novel
      isoform of WIP consisting of a truncated 403 a.a. long protein that includes the
      377 a.a. encoded by the first 4 exons of WIP followed by a 26 a.a. sequence
      encoded by intron 4.

PMID- 17207459
TI  - A critical role of LFA-1 in the development of Th17 cells and induction of
      experimental autoimmune encephalomyelytis.
AB  - The alphaLbeta2 integrin adhesion molecule LFA-1 is believed to be involved in
      the migration of autoreactive T cells to the central nervous system across the
      endothelial blood-brain barrier in experimental autoimmune encephalomyelitis
      (EAE). Here, we demonstrate that the incidence and clinical scores of EAE in LFA
      1-/- mice induced by the immunization with the myelin oligodendrocyte
      glycoprotein (MOG)-peptide antigen were significantly lower than those in wild
      type mice. Further studies demonstrated that lymphocytes recruitment to the
      draining lymph nodes (dLN) after the immunization with the MOG-peptide was
      severely suppressed in LFA-1-/- mice. Moreover, generation of the MOG-specific IL
      17-producing helper T (Th17) cells in the dLN was impaired in LFA-1-/- mice.
      These results suggest that LFA-1 may play an important role for the generation of
      MOG-specific Th17 cells in the dLN as well as the immigration of MOG-specific
      naive CD4+ T cells to the dLN.

PMID- 17207460
TI  - Diversity within the JMJD2 histone demethylase family.
AB  - JMJD2A-D belong to the JmjC domain-containing family of histone demethylases.
      JMJD2D is the most structurally divergent JMJD2 protein as it lacks the PHD and
      Tudor domains present in JMJD2A-C. Here, we systematically analyzed the histone
      demethylase specificity of JMJD2 proteins in vivo. We found that JMJD2A and C
      demethylate tri- and dimethylated H3K9 and H3K36, whereas JMJD2D demethylates tri
      , di-, and monomethylated H3K9. Enzymatic activity requires the N-terminal JmjN
      domain. It also contributes to efficient nuclear localization together with the
      PHD and Tudor domains of JMJD2A and C. Furthermore, JMJD2 proteins form homomers,
      and JMJD2A and C, but not JMJD2D, can also heteromerize. Finally, we show that
      JMJD2 proteins promoter-specifically repress or activate gene transcription.
      Altogether, our results reveal novel properties of and functional differences
      between JMJD2 proteins that may therefore have different effects on chromatin
      structure.

PMID- 17207461
TI  - The suppression of zfpm-1 accelerates the erythropoietic differentiation of human
      CD34+ cells.
AB  - Erythropoiesis is a complex multistage process for the differentiation of mature
      erythrocytes from hematopoietic stem cells. The function of several transcription
      factors has been reported in hematopoietic stem cell differentiation. However,
      the molecular basis governing its functional behavior is unclear. In this study,
      we characterized the role of Zfpm-1 during the erythropoietic differentiation of
      human hematopoietic stem cells. To verify the function of Zfpm-1 during
      erythropoietic differentiation, we established human CD34+ cell culture system by
      using human umbilical cord blood. At day 7 of the human CD34+ cell
      differentiation process to proerythocytes, Zfpm-1 was initially up-regulated and
      then dramatically down-regulated at day 9. The Zfpm-1 siRNA transfected HSCs
      contained 20% more GPA+ cells than the mock transfected cells, and showed
      repressed expression of the hematopoietic transcription factors, c-myc and c-myb,
      but increased expression of GATA-1. In contrast, the Zfpm-1 gain-of-function is
      the opposite of loss-of-function results above.

PMID- 17207462
TI  - In vivo dynamics of enterovirus protease revealed by fluorescence resonance
      emission transfer (FRET) based on a novel FRET pair.
AB  - An in vivo protease assay suitable for analysis by fluorescence resonance energy
      transfer (FRET) was developed on the basis of a novel FRET pair. The specifically
      designed fusion substrate consists of green fluorescent protein 2 (GFP2)-peptide
      red fluorescent protein 2 (DsRed2), with a cleavage motif for the enterovirus 2A
      protease (2Apro) embedded within the peptide region. FRET can be readily
      visualized in real-time from cells expressing the fusion substrate until a
      proteolytic cleavage by 2Apro from the input virus. The level of FRET decay is a
      function of the amount and infection duration of the inoculated virus as measured
      by a fluorometer assay. The FRET biosensor also responded well to other related
      enteroviruses but not to a phylogenetically distant virus. Western blot analysis
      confirmed the physical cleavage of the fusion substrate upon the infections. The
      study provides proof of principle for applying the FRET technology to
      diagnostics, screening procedures, and cell biological research.

PMID- 17207463
TI  - Rac1 activity is required for cardiac myocyte alignment in response to mechanical
      stress.
AB  - Mechanical stretch is essential for the cardiac growth. The exposure of cardiac
      myocytes to the mechanical stretch leads to the cell alignment in parallel to the
      stretch direction, determining the cell polarity, though it remains to be
      addressed how mechanical stretch regulates cell orientation. In the present
      study, we investigated the signal transduction pathways responsible for the cell
      orientation response to mechanical stretch, focusing on Rho family proteins.
      Neonatal rat cardiomyocytes were cultured on silicon chambers and exposed to
      artificial uniaxial cyclic stretch. The pull-down assays revealed that Rac1 was
      rapidly activated by stretch, but not RhoA. To analyze the roles of Rho family
      proteins in cardiomyocyte orientation, adenoviral vectors expressing dominant
      negative (dn) RhoA and Rac1 were generated. The transfection with adenovirus
      vector expressing dnRac1, but not dnRhoA, inhibited stretch-induced cell
      alignment. In conclusion, Rac1 activity is necessary for cardiomyocyte alignment
      in response to directional stretch.

PMID- 17207464
TI  - Investigation of binding proteins for anti-platelet agent K-134 by Drug-Western
      method.
AB  - K-134 ((-)-6-[3-[3-cyclopropyl-3-[(1R, 2R)-2-hydroxycyclohexyl]ureido]-propoxy]
      2(1H)-quinolinone) is a novel anti-platelet agent with anti-hyperplastic
      activities. We found previously that K-134 is a potent phosphodiesterase-3 (PDE3)
      inhibitor. In the present study, we found other K-134-binding proteins by Drug
      Western method. We isolated two clones that can bind directly to K-134, cofilin
      2, and CD36 in vitro. Comparison of their amino acid sequences showed similarity
      over a short stretch [KxxxxVxIxWxxE] in part in the collagen-binding region of
      CD36. K-134 inhibited binding between CD36 and collagen type-I; however, other
      PDE3 inhibitors, cilostazol, amrinone, and an inactive derivative of K-134, 4S-OH
      K-134, showed little or no effect on binding. It was strongly suggested that the
      direct binding between K-134 and CD36 is a characteristic effect of K-134, and
      the homologous stretch may be necessary for binding to K-134. These results also
      suggested that these interactions are involved in the mechanisms of the anti
      platelet and anti-hyperplastic effects of K-134.

PMID- 17207465
TI  - Phylogenetic profiles for the prediction of protein-protein interactions: how to
      select reference organisms?
AB  - The phylogenetic profile method has been widely applied in the prediction of
      protein-protein interactions (PPIs). Studies often use all of the available
      complete genomes for this method. With more than 400 genomes complete and new
      ones on the horizon, it remains unclear how to select reference organisms for
      profile construction and then influence the PPI prediction. Here, we performed a
      systematic assessment of reference organism selection from 225 complete genomes
      with their evolutionary tree. Our results suggest that reference organisms should
      be selected from moderately and highly genetically distant organisms, from all
      three domains (Bacteria, Archaea, and Eukarya), and by their even distribution at
      the fifth hierarchical level in the evolutionary tree. Our study provides
      important guidance on the construction of phylogenetic profiles for PPI
      prediction and functional genomics, which has become challenging due to the large
      and increasing number of available candidate organisms.

PMID- 17207466
TI  - The N-terminal domain of alphaB-crystallin is protected from proteolysis by bound
      substrate.
AB  - Alpha-crystallin, a major structural protein of the lens can also function as a
      molecular chaperone by binding to unfolding substrate proteins. We have used a
      combination of limited proteolysis at low temperature, and mass spectrometry to
      identify the regions of alpha-crystallin directly involved in binding to the
      structurally compromised substrate, reduced alpha-lactalbumin. In the presence of
      trypsin, alpha-crystallin which had been pre-incubated with substrate showed
      markedly reduced proteolysis at the C-terminus compared with a control,
      indicating that the bound substrate restricted access of trypsin to R157, the
      main cleavage site. Chymotrypsin was able to cleave at residues in both the N-
      and C-terminal domains. In the presence of substrate, alpha-crystallin showed
      markedly reduced proteolysis at four sites in the N-terminal domain when compared
      with the control. Minor differences in cleavage were observed within the C
      terminal domain suggesting that the N-terminal region of alpha-crystallin
      contains the major substrate interaction sites.

PMID- 17207467
TI  - TRB3 modulates C2C12 differentiation by interfering with Akt activation.
AB  - TRB3 is a member of TRB protein family characterized by containing a variant
      kinase domain without enzymatic activity. Interacting with Ser/Thr protein
      kinases Akt, TRB3 impairs Akt activation induced by growth factors and insulin.
      In this study we have examined the potential role of TRB3 in muscle
      differentiation. Our data indicated that the expression of TRB3 is downregulated
      during C2C12 cells undergoing muscle differentiation and that overexpression of
      TRB3 inhibits Akt activation during differentiation. Correspondingly,
      overexpression of TRB3 inhibits, while knockdown TRB3 enhances C2C12
      differentiation. Thus, our studies indicated that TRB3 plays a critical role in
      muscle differentiation.

PMID- 17207468
TI  - BTM-P1 polycationic peptide biological activity and 3D-dimensional structure.
AB  - The novel BTM-P1 peptide interferes with energetic processes in mitochondria; its
      antimicrobial activity against Gram-positive and Gram-negative bacteria is
      described here. BTM-P1 three-dimensional structure was determined by 1H NMR to
      explain its biological mechanisms and membrane activity. Structural data
      indicated that BTM-P1 can form an alpha-helix; circular dichroism analysis
      confirmed the peptide's propensity to behave as a typical transmembrane helix in
      a lipidic environment. According to the structural characteristics of the
      polycationic BTM-P1 peptide so revealed, its biological activity can be explained
      by a mechanism involving the formation of ion-permeable channels in biomembranes.

PMID- 17207469
TI  - Ethylene responsive element binding protein 1 (StEREBP1) from Solanum tuberosum
      increases tolerance to abiotic stress in transgenic potato plants.
AB  - To identify components of the plant stress signal transduction cascade and
      response mechanisms, we screened plant genes using reverse Northern blot
      analysis, and chose the ethylene responsive element binding protein 1 (StEREBP1)
      for further characterization. To investigate its biological function in the
      potato, we performed Northern blot analysis and observed enhanced levels of
      transcription in response to several environmental stresses including low
      temperature. In vivo targeting experiments using a green fluorescent protein
      (GFP) reporter indicated that StEREBP1 localized to the nucleus of onion
      epidermal cells. StEREBP1 was found to bind to GCC and DRE/CRT cis-elements and
      both microarray and RT-PCR analyses indicated that overexpression of StEREBP1
      induced expression of several GCC box-containing stress response genes. In
      addition, overexpression of StEREBP1 enhanced tolerance to cold and salt stress
      in transgenic potato plants. The results of this study suggest that StEREBP1 is a
      functional transcription factor that may be involved in abiotic stress responses
      in plants.

PMID- 17207470
TI  - Relationship of dietary intake to gastrointestinal symptoms in children with
      autistic spectrum disorders.
AB  - BACKGROUND: Gastrointestinal (GI) symptoms and abnormalities in stool consistency
      are frequently reported by parents of children with autism spectrum disorders
      (ASD). The purpose of this study was to 1) describe dietary intake of a cohort of
      children with ASD compared with normative data and 2) determine whether GI
      symptoms and stool consistency are related to dietary intake. METHODS: Data from
      diet diaries of children (3-8 years) with ASD (n = 62) were analyzed by a
      registered pediatric dietician to compare to RDA standards for total calories,
      protein, carbohydrate, and fat. Dietary intake was correlated with descriptors of
      stool consistency using cumulative logistic regression methods. RESULTS: Intake
      of calories, carbohydrates, and fat were in the average range; protein intake was
      increased (211% of RDA). Reported frequency of GI abnormalities, including
      abnormal stool consistency (e.g., bulky or loose), was increased (54%). No
      statistically significant relationships between stool consistency and dietary
      intake were observed. CONCLUSIONS: In this sample, there was a high rate of
      reported gastrointestinal symptoms, despite lack of medical causes. Intake was
      adequate for calories and carbohydrates and increased for protein. The children
      did not exhibit excessive carbohydrate intake. There was no association of
      nutrient intake to changes in stool consistency.

PMID- 17207471
TI  - Antibodies to infectious agents in individuals at ultra-high risk for psychosis.
AB  - BACKGROUND: While there is evidence that some cases of schizophrenia may be
      associated with microbial infections, the role of microbial agents has not been
      investigated in people with emerging psychosis. METHODS: Participants were 105
      help seeking ultra-high risk individuals. Psychiatric measures included the Brief
      Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms.
      Serum IgG antibodies against human herpesviruses and Toxoplasma gondii were
      determined using immunoassay methods. Multiple linear regression with adjustment
      for age and sex was applied to test associations between serum antibodies and
      psychiatric measures. RESULTS: Higher levels of serum IgG antibodies against
      Toxoplasma gondii in Toxoplasma-positive individuals were significantly
      associated with more severe positive psychotic symptoms. No significant
      association was observed between antibody levels and psychiatric measures in
      individuals positive for human herpesviruses. CONCLUSIONS: In some individuals
      infection with Toxoplasma gondii may be an environmental factor contributing to
      the manifestation of positive psychotic symptoms.

PMID- 17207472
TI  - Persistent disruption of a traumatic memory by postretrieval inactivation of
      glucocorticoid receptors in the amygdala.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is characterized by acute and
      chronic changes in the stress response, which include alterations in
      glucocorticoid secretion and critically involve the limbic system, in particular
      the amygdala. Important symptoms of PTSD manifest as a classical conditioning to
      fear, which recurs each time trauma-related cues remind the subject of the
      original insult. Traumatic memories based on fear conditioning can be disrupted
      if interfering events or pharmacological interventions are applied following
      their retrieval. METHODS AND RESULTS: Using an animal model, here we show that a
      traumatic memory is persistently disrupted if immediately after its retrieval
      glucocorticoid receptors are inactivated in the amygdala. The disruption of the
      memory is long lasting and memory retention does not re-emerge following strong
      reminders of the conditioned fear. CONCLUSIONS: We propose that a combinatorial
      approach of psychological and pharmacological intervention targeting the
      glucocorticoid system following memory retrieval may represent a novel direction
      for the treatment of PTSD.

PMID- 17207473
TI  - Post-pubertal disruption of medial prefrontal cortical dopamine-glutamate
      interactions in a developmental animal model of schizophrenia.
AB  - BACKGROUND: A neonatal ventral hippocampal lesion (NVHL) induces behavioral and
      physiological anomalies mimicking pathophysiological changes of schizophrenia.
      Because prefrontal cortical (PFC) pyramidal neurons recorded from adult NVHL rats
      exhibit abnormal responses to activation of the mesocortical dopaminergic (DA)
      system, we explored whether these changes are due to an altered DA modulation of
      pyramidal neurons. METHODS: Whole-cell recordings were used to examine the
      effects of DA and glutamate agonists on cell excitability in brain slices
      obtained from pre- (postnatal day [PD] 28-35) and post-pubertal (PD > 61) sham
      and NVHL animals. RESULTS: N-methyl d-aspartate (NMDA), alpha-amino-3-hydroxy-5
      methylisoxazole propionate (AMPA), and the D(1) agonist SKF38393 increased
      excitability of deep layer pyramidal neurons in a concentration-dependent manner.
      The opposite effect was observed with the D(2) agonist quinpirole. The effects of
      NMDA (but not AMPA) and SKF38393 on cell excitability were significantly higher
      in slices from NVHL animals, whereas quinpirole decrease of cell excitability was
      reduced. These differences were not observed in slices from pre-pubertal rats,
      suggesting that PFC DA and glutamatergic systems become altered after puberty in
      NVHL rats. CONCLUSIONS: A disruption of PFC dopamine-glutamate interactions might
      emerge after puberty in brains with an early postnatal deficit in hippocampal
      inputs, and this disruption could contribute to the manifestation of
      schizophrenia-like symptoms.

PMID- 17207474
TI  - 5-HT6 receptor antagonist SB-399885 potentiates haloperidol and risperidone
      induced dopamine efflux in the medial prefrontal cortex or hippocampus.
AB  - Many studies suggest that the 5-HT6 receptors are involved, along with other 5-HT
      receptors, in the pathophysiology and pharmacotherapy of schizophrenia. It is a
      putative therapeutic target of atypical antipsychotic drugs, notably clozapine,
      as well as some other psychotropic agents. Preferential potentiation of dopamine
      (DA) efflux in the medial prefrontal cortex (mPFC) and hippocampus (HIP) has been
      suggested to contribute to the ability of atypical antipsychotic drugs (APDs),
      e.g. clozapine, risperidone, olanzapine and ziprasidone, to improve cognitive
      function in schizophrenia. The present study demonstrated that SB-399885, a
      selective 5-HT6 receptor antagonist, at doses of 3 and 10 mg/kg, had no effect on
      cortical DA release in freely moving rats. However, both doses of SB-399885
      slightly but significantly increased DA release in the HIP. Of particular
      interest, SB-399885, 3 mg/kg, significantly potentiated the ability of a typical
      antipsychotic drug haloperidol, a D2 receptor antagonist, at a dose of 0.1 mg/kg,
      to increase DA release in the HIP but not the mPFC. The atypical antipsychotic
      drug risperidone, a multireceptor antagonist, which lacks 5-HT6 receptor
      antagonist properties, at doses of 0.1, 0.3 and 1.0 mg/kg, produced a bell-shaped
      dose response effect on DA efflux in the mPFC and HIP. SB-399885 potentiated
      risperidone (1.0 mg/kg)-induced DA efflux in both regions. The increase in the
      HIP, but not the mPFC, DA efflux by 0.3 mg/kg risperidone was also potentiated by
      SB-399885, 3 mg/kg. These results suggest that the combined blockade of 5-HT6 and
      D2 receptors may contribute to the potentiation of haloperidol- and risperidone
      induced DA efflux in the mPFC or HIP. The present data provides additional
      evidence in support of a possible therapeutic role for 5-HT6 receptor antagonism,
      as an addition on therapy, to enhance cognitive function in schizophrenia.

PMID- 17207477
TI  - Methodologies, bioindicators, and biomarkers for assessing gender-related
      differences in wildlife exposed to environmental chemicals.
AB  - Male and female organisms may have significant differences in their exposure,
      toxicokinetics, and response to chemicals, but gender effects have received
      relatively little attention, often viewed as a confounder rather than of primary
      importance. In this paper, we examine some of the key issues and methodologies
      for incorporating gender in studies of the effects of chemicals on wildlife, and
      explore bioindicators and biomarkers of gender effects. Examining gender-related
      differences in response to chemicals is complicated in wildlife because of the
      vast array of species, and differences in niches, lifespans, reproductive cycles
      and modes, and population dynamics. Further, organisms are more at risk in some
      ecosystems than others, which may increase the magnitude of effects. Only by
      studying wild animals, especially native species, can we truly understand the
      potential impact of gender-specific effects of chemical exposure on populations.
      Several factors affect gender-related differences in responses to chemicals,
      including exposure, age, size, seasonality, and genetic and phenotypic variation.
      There are clear examples where gender-related differences have had significant
      effects on reproductive success and population stability, including
      destabilization of gamete release in invertebrates, and alterations of endocrine
      and neuroendocrine system functioning in vertebrates. A wide range of new
      technologies and methods are available for examining gender-related differences
      in responses to chemicals. We provide examples that show that there are gender
      related differences in responses to chemicals that have significant biological
      effects, and these gender-related differences should be taken into account by
      scientists, regulators, and policy makers, as well as the public.

PMID- 17207475
TI  - Ovarian granulosa cell survival and proliferation requires the gonad-selective
      TFIID subunit TAF4b.
AB  - Oocyte development in the mammalian ovary requires productive interactions with
      somatic granulosa cells of the ovarian follicle. Proliferating granulosa cells
      support the progression of follicular growth and maturation, multiplying
      dramatically as it unfolds. The cell cycle recruitment of granulosa cells is
      regulated at least in part by hormones such as follicle-stimulating hormone (FSH)
      and estrogen. Follicles recruited into the growth phase following formation of
      multiple layers of granulosa cells have two major fates: either to continue
      proliferation followed by differentiation, or to die by programmed cell death, or
      atresia. While many of the signaling pathways orchestrating ovarian follicle
      development are known, the downstream transcriptional regulators that integrate
      such signals in the mammalian ovary remain to be defined. Recent experiments in
      diverse organisms have revealed multiple instances of gonad-selective components
      of the basal transcriptional machinery. One such protein, TAF4b, is a gonadal
      enriched coactivator subunit of the TFIID complex required for normal female
      fertility in the mouse. To determine the etiology of female infertility of the
      TAF4b-deficient mice, we have determined multiple functions of TAF4b during
      postnatal ovarian follicle development. Here we demonstrate that the TAF4b
      protein is expressed in the granulosa cell compartment of the mammalian ovarian
      follicle. Furthermore, TAF4b-deficient mouse ovaries contain reduced numbers of
      primordial as well as growing follicles and a concomitant increased proportion of
      apoptotic follicles in comparison to wild type counterparts. Importantly, TAF4b
      null follicles are largely resistant to induction of proliferation in response to
      multiple hormonal stimuli including estrogen and FSH and demonstrate compromised
      granulosa cell survival. Together, these data suggest that TAF4b integrates a
      program of granulosa cell gene expression required for normal ovarian follicle
      survival and proliferation in response to diverse ovarian signaling events.

PMID- 17207476
TI  - Role of retinoic acid during forebrain development begins late when Raldh3
      generates retinoic acid in the ventral subventricular zone.
AB  - Retinoic acid (RA) synthesized by Raldh3 in the frontonasal surface ectoderm of
      chick embryos has been suggested to function in early forebrain patterning by
      regulating Fgf8, Shh, and Meis2 expression. Similar expression of Raldh3 exists
      in E8.75 mouse embryos, but Raldh2 is also expressed in the optic vesicle at this
      stage suggesting that both genes may play a role in early forebrain patterning.
      Furthermore, Raldh3 is expressed later in the forebrain itself (lateral
      ganglionic eminence; LGE) starting at E12.5, suggesting a later role in forebrain
      neurogenesis. Here we have analyzed mouse embryos carrying single or double null
      mutations in Raldh2 and Raldh3 for defects in forebrain development. Raldh2(-/
      );Raldh3(-/-) embryos completely lacked RA signaling activity in the early
      forebrain, but exhibited relatively normal expression of Fgf8, Shh, and Meis2 in
      the forebrain. Thus, we find no clear requirement for RA in controlling
      expression of these important forebrain patterning genes, but Raldh3 expression
      in the frontonasal surface ectoderm was found to be needed for normal Fgf8
      expression in the olfactory pit. Our studies revealed that later expression of
      Raldh3 in the subventricular zone of the LGE is required for RA signaling
      activity in the ventral forebrain. Importantly, expression of dopamine receptor
      D2 in E18.5 Raldh3(-/-) embryos was essentially eliminated in the developing
      nucleus accumbens, a tissue lying close to the source of RA provided by Raldh3.
      Our results suggest that the role of RA during forebrain development begins late
      when Raldh3 expression initiates in the ventral subventricular zone.

PMID- 17207478
TI  - Effect of antimuscarinic drugs used for overactive bladder on learning in a rat
      passive avoidance response test.
AB  - Antimuscarinic drugs are used for the treatment of overactive bladder. One
      adverse effect associated with their use, however, is cognitive impairment
      arising from their anticholinergic action. Here, we examined the effects of
      antimuscarinic drugs on learning using a passive avoidance task in rats. Drugs
      were intravenously administered 10 min before an acquisition trial, followed 24 h
      later by measurement of latency time in the passive avoidance task in a retention
      trial. Oxybutynin (0.1-1 mg/kg i.v.), propiverine (1-10 mg/kg i.v.) and
      scopolamine (0.1-1 mg/kg i.v.) impaired learning at doses of 0.3 mg/kg i.v. or
      more, 10 mg/kg i.v., and 0.3 mg/kg i.v. or more, respectively. Tolterodine (0.1-1
      mg/kg i.v.) tended to impair these functions at a dose of 1 mg/kg i.v. In
      contrast, darifenacin (0.1-1 mg/kg i.v.) and solifenacin (0.3-3 mg/kg i.v.)
      showed no impairment of these functions. We also examined the effects of
      antimuscarinic drugs on learning enhanced by the cholinesterase inhibitor
      donepezil at a dose of 0.1 mg/kg i.v. in scopolamine-treated rats. Oxybutynin
      (0.1-1 mg/kg i.v.) impaired these donepezil-enhanced functions, whereas
      solifenacin (0.3-3 mg/kg i.v.) produced no significant impairment. These results
      suggest that antimuscarinic drugs such as darifenacin, solifenacin and
      tolterodine may have less effect on cognitive function in the treatment of
      patients with overactive bladder.

PMID- 17207479
TI  - Altered antinociceptive efficacy of tramadol over time in rats with painful
      peripheral neuropathy.
AB  - Pain due to peripheral nerve injury or disease is a dynamic process, such that
      the mechanism that underlies it alters over time. Tramadol has been reported to
      be analgesic in clinical neuropathic pain, with varying levels of efficacy due to
      a patient population that has had neuropathic pain for a wide range of time. In
      order to address and examine the issue, the antinociceptive efficacy of tramadol
      over time was tested in rats with a chronic constriction injury (CCI) of the left
      sciatic nerve. Rats developed a robust hind paw hypersensitivity to innocuous
      mechanical stimulation ipsilateral to CCI surgery. Subcutaneous injection of
      tramadol in rats two weeks after CCI surgery dose-dependently attenuated
      mechanical hypersensitivity, which was abolished with the mu-opioid receptor
      antagonist naloxone but not the alpha(2)-adrenoceptor antagonist yohimbine.
      Systemic tramadol also attenuated mechanical hypersensitivity four weeks after
      CCI surgery, but the efficacy significantly diminished at this time point. In
      addition, the effect of tramadol at this later time point could be reduced with
      yohimbine as well as naloxone. These data demonstrate that the efficacy of
      tramadol depends in part on the duration of nerve injury-evoked nociception, and
      that its antinociceptive mechanism changes over time. Alteration in
      antinociceptive mechanism over time may explain the inconsistency in efficacy of
      this and other analgesic drugs in chronic pain patients.

PMID- 17207480
TI  - Differential regulation of the signaling and trafficking of the two prostaglandin
      D2 receptors, prostanoid DP receptor and CRTH2.
AB  - Prostaglandin D2 (PGD2) exerts its actions on two G protein-coupled receptors,
      the prostanoid DP receptor and CRTH2 (chemoattractant homologous receptor
      expressed on TH2 cells). Here, we characterize the regulation of the signaling
      and trafficking of the prostanoid DP receptor and CRTH2. Time-course and dose
      response curves showed that both receptors expressed in HEK293 cells internalized
      maximally after 2 h of stimulation with 1 microM PGD2. Co-expression of the G
      protein-coupled receptor kinases GRK2, GRK5 or GRK6 increased agonist-induced
      internalization of CRTH2, while only GRK2 had an effect on the internalization of
      the prostanoid DP receptor. Protein kinase C (PKC) activation stimulated the
      internalization of both receptors. Interestingly, only PGD2-induced
      internalization of CRTH2, and not of prostanoid DP receptor, was decreased by
      inhibition of PKC or protein kinase A (PKA). Our data also indicate that CRTH2 is
      subjected to basal phosphorylation by PKA, which appears to be involved in CRTH2
      internalization. Prostanoid DP receptor internalization was promoted by co
      expression of arrestin-2 and -3, while the internalization of CRTH2 was increased
      by co-expression of arrestin-3 only. The detection of prostanoid DP receptor and
      CRTH2 internalization was reduced by the co-expression of Rab4 and Rab11,
      respectively, suggesting differential regulation of receptor recycling. Moreover,
      immunofluorescence microscopy experiments showed that the prostanoid DP receptor
      specifically co-localized with Rab4, and CRTH2 with Rab11. The signaling of the
      prostanoid DP receptor was regulated by GRK2 overexpression, while that of CRTH2
      was modulated by overexpression of GRK2, -5 and -6. Our results show a
      differential regulation of the prostanoid DP receptor and CRTH2, two receptors
      for PGD2.

PMID- 17207481
TI  - Babesia bovis: subcellular localization of host erythrocyte membrane components
      during their asexual growth.
AB  - In the present study, the subcellular localization of the host red blood cell
      (RBC) membrane components, the alpha2-3-linked sialic acid (SA) residues and the
      lipid bilayer, was observed during the asexual growth of Babesia bovis using two
      erythrocyte probes, the SA-specific lectin (MALII) and the lipophilic fluorescent
      (PKH2) probes, respectively. In confocal laser scanning microscopy with MALII,
      the SA residues on the surface of parasitized RBCs appeared to accumulate into
      the intracellular parasites as the parasites matured as well as to remain on the
      surface of extracellular parasites. Furthermore, when PKH2-labeled RBCs were
      infected with B. bovis, PKH2 signals were also observed around both the
      intracellular and the extracellular parasites, similarly to the results of MALII.
      These results indicated that the components derived from the host erythrocyte
      membrane are incorporated into the intracellular parasites during their asexual
      growth within the parasitized RBC, suggesting the possible formation of a
      parasitophorous vacuole-based network or a parasite surface coat.

PMID- 17207482
TI  - Histone H1 regulates chromatin condensation in Leishmania parasites.
AB  - We investigated the functional role of the Leishmania histone H1 and demonstrate
      for the first time that addition of histone H1 has a strong effect on microccocal
      digestion, chromatin condensation of parasite nuclei and that its overexpression
      can modulate parasite infectivity in vivo.

PMID- 17207483
TI  - Identification of an amyloidogenic region on keratoepithelin via synthetic
      peptides.
AB  - Mutations of keratoepithelin (KE) gene in human chromosome 5q31 have been linked
      with corneal epithelial or stromal dystrophies characterized by the abnormal
      deposits of amyloid fibrils and/or non-amyloid aggregations in corneal tissue. We
      report herein that synthetic peptide containing amino acid (a.a.) residues of 515
      532 of native KE protein can readily form beta-sheet-containing amyloid fibrils
      in vitro. Amyloid fibrils formed in various conditions from short synthetic
      peptides (containing a.a. 515-532 and 515-525, respectively) were characterized
      by thioflavin T (ThT) fluorescence assay, Congo red staining, electron microscopy
      (EM) and circular dichroism (CD). Triple-N-methylation of the synthetic peptides
      prevented the beta-sheet polymerization and related amyloid fibril formation.
      Comparison study with ThT fluorescence further demonstrated that synthetic
      peptides containing corneal dystrophy-related mutations within this region formed
      amyloid fibrils to various extents. Our results suggest that each individual
      dystrophy-related mutation by itself does not necessarily potentiate amyloid
      fibril formation of KE. Roles of these intrinsically amyloidogenic foci in
      abnormal KE aggregations and amyloid deposits of stromal corneal dystrophies
      await further investigation.

PMID- 17207484
TI  - A needle in a haystack: the active site of the membrane-bound complex cytochrome
      c nitrite reductase.
AB  - Cytochrome c nitrite reductase is a multicenter enzyme that uses a five
      coordinated heme to perform the six-electron reduction of nitrite to ammonium. In
      the sulfate reducing bacterium Desulfovibrio desulfuricans ATCC 27774, the enzyme
      is purified as a NrfA2NrfH complex that houses 14 hemes. The number of closely
      spaced hemes in this enzyme and the magnetic interactions between them make it
      very difficult to study the active site by using traditional spectroscopic
      approaches such as EPR or UV-Vis. Here, we use both catalytic and non-catalytic
      protein film voltammetry to simply and unambiguously determine the reduction
      potential of the catalytic heme over a wide range of pH and we demonstrate that
      proton transfer is coupled to electron transfer at the active site.

PMID- 17207485
TI  - Ectopic spleen presenting as a pelvic mass.

PMID- 17207487
TI  - Acanthamoeba invasion of the central nervous system.
AB  - Pathogenic Acanthamoeba are known to infect the CNS, resulting in fatal
      granulomatous encephalitis. The mechanisms associated with the pathogenesis
      remain unclear; however pathophysiological complications involving the CNS most
      likely include induction of pro-inflammatory responses, invasion of the blood
      brain barrier and the connective tissue and neuronal damage leading to brain
      dysfunction. The routes of entry include the olfactory neuroepithelium pathway
      and/or lower respiratory tract, followed by haematogenous spread. Skin lesions
      may provide direct entry into the bloodstream, bypassing the lower respiratory
      tract. For the haematogenous route, entry of amoebae into the CNS most likely
      occurs at the sites of the blood-brain barrier. Recent studies have identified
      several molecular mechanisms associated with Acanthamoeba traversal of the blood
      brain barrier and targeting those may help develop therapeutic interventions
      and/or design preventative strategies.

PMID- 17207486
TI  - Effects on growth, hemoglobin metabolism and paralogous gene expression resulting
      from disruption of genes encoding the digestive vacuole plasmepsins of Plasmodium
      falciparum.
AB  - Four of the plasmepsins of Plasmodium falciparum are localised in the digestive
      vacuole (DV) of the asexual blood stage parasite (PfPM1, PfPM2, PfPM4 and PfHAP),
      and each of these aspartic proteinases has been successfully targeted by gene
      disruption. This study describes further characterisation of the single
      plasmepsin knockout mutants, and the creation and characterisation of double
      plasmepsin knockout mutants lacking complete copies of pfpm2 and pfpm1 or pfhap
      and pfpm2. Double-plasmepsin knockout mutants were created by transfecting pre
      existing knockout mutants with a second plasmid knockout construct. PCR and
      Southern blot analysis demonstrate the integration of a large concatamer of each
      plasmid construct into the targeted gene. All mutants have been characterised to
      assess the involvement of the DV plasmepsins in sustaining growth during the
      asexual blood stage. Analyses reaffirmed that knockout mutants Deltapfpm1 and
      Deltapfpm4 had lower replication rates in the asexual erythrocytic stage than the
      parental line (Dd2), but double-plasmepsin knockout mutants lacking intact copies
      of either pfpm2 and pfpm1, or pfpm2 and pfhap, had normal growth rates compared
      with Dd2. The amount of crystalline hemozoin produced per parasite during the
      asexual cycle was measured in each single-plasmepsin knockout to estimate the
      effect of each DV plasmepsin on hemoglobin digestion. Only Deltapfpm4 had a
      statistically significant reduction in hemozoin accumulation, indicating that
      hemoglobin digestion was impaired in this mutant. In the single-plasmepsin
      knockouts, no statistically significant differences were found in the steady
      state levels of mRNA from the remaining intact DV plasmepsin genes. Disruption of
      a DV plasmepsin gene does not affect the accumulation of mRNA encoding the
      remaining paralogous plasmepsins, and Western blot analysis confirmed that the
      accumulation of the paralogous plasmepsins in each knockout mutant was similar
      among all clones examined.

PMID- 17207488
TI  - Stress-strain behavior of the passive basilar artery in normotension and
      hypertension.
AB  - Vascular cells are very responsive to even subtle changes in their local
      mechanical environment, thus there is a pressing need to quantify normal states
      of stress and strain as well as any perturbations from these normal states.
      Toward this end, we must quantify constitutive behaviors for both normal and
      adapted (maladapted) arteries. In this note, we report the first quantification
      of changes in the biaxial mechanical behavior of the passive basilar artery due
      to hypertension.

PMID- 17207489
TI  - Odour fingerprint acquisition by means of comprehensive two-dimensional gas
      chromatography-olfactometry and comprehensive two-dimensional gas
      chromatography/mass spectrometry.
AB  - The analysis of complex matrices, such as perfumes, by means of gas
      chromatography-olfactometry (GC-O) can be rather imprecise due to the co
      elutions, leading to a possible masking of odour-active trace-level compounds by
      major interferences or agglomeration of olfactive impressions resulting in
      unreliable olfactive characterization. To overcome these limits an innovative
      technique, comprehensive two-dimensional gas chromatography-olfactometry (GC x GC
      O), was applied, revealing several relevant co-elutions, as in the linalool and
      linalyl acetate zones. A total of 177 compounds, out of these 135 odour-active,
      were detected by GC-O, while about 481 out of 818 compounds presented odour
      activity through GC x GC-O analyses. In addition, GC/mass spectrometry (GC/MS)
      and GC x GC/MS analyses were also performed. Peak assignment was achieved by
      means of different information sources, such as GC/MS, GC x GC/MS, LRI, injection
      of standards and olfactive impressions.

PMID- 17207490
TI  - Pseudo-homogeneous micelle extraction of ion-associates formed between
      tetrabutylammonium ion and some aromatic sulfonate ions into nonionic surfactant
      micelle studied through the mobility measurements in capillary zone
      electrophoresis.
AB  - Ion-association extraction of some aromatic sulfonate ions including alkylbenzene
      sulfonates with tetrabutylammonium ion (TBA+) into nonionic surfactant micelle
      has been investigated through the changes in the electrophoretic mobility.
      Nonionic surfactants of Brij 35 and Brij 58 were used as micelle substrates to
      which the ion-associates formed could distribute. The electrophoretic mobility of
      the aromatic sulfonate ions was measured by capillary zone electrophoresis in the
      presence of TBA+ and/or the nonionic surfactant to determine ion-association
      constants (K(ass)), binding constants of the anions to the nonionic surfactant
      micelle (K(B)), and binding constants of the ion-associates to the nonionic
      surfactant micelle (K(B,IA)). Nonlinear phenomena induced with the alkyl chain
      moiety were observed on K(ass) and K(B) by its linear structure and the mixed
      micelle formation, respectively. Larger K(B) values were obtained with Brij 58 as
      micelle matrix than with Brij 35, while the differences in K(B,IA) were small
      between Brij 58 and Brij 35.

PMID- 17207491
TI  - Capillary ion chromatography of inorganic anions on octadecyl silica monolith
      modified with an amphoteric surfactant.
AB  - A reversed-phase monolithic silica based capillary column (Onyx C(18), 150 mm x
      0.1 mm) was modified with the amphoteric surfactant, N-dodecyl-N,N
      (dimethylammonio)undecanoate (DDMAU) and evaluated for the separation and
      determination of inorganic anions using on-column capacitively coupled
      contactless conductivity detection (C(4)D). The chromatographic performance of
      the column was evaluated and under optimal conditions separation efficiencies of
      56,200 plates per meter or 7025 plates per column (at detection point) were
      observed (for iodide). Direct plumbing of the capillary column to the micro
      injector and on-column detection eliminated extra-column band broadening, thus
      allowing accurate analysis of van Deemter curves obtained for the monolithic
      capillary column. The calculated value for the C-term in the obtained van Deemter
      curve was between 3 and 4 ms for inorganic anions, allowing for the utilisation
      of relatively high flow rates without significant losses in efficiency. The
      performance of the C(4)D detector was investigated and compared for detection on
      an open tubular capillary column and on the modified monolithic silica capillary
      column. The on-column detection approach did not result in any significant
      decrease in peak sensitivity for the monolith compared to responses recorded for
      open tubular capillary columns, and in addition meant the system could be applied
      to rapid separations by simple variation in apparent column length. The proposed
      chromatographic system allowed for detection of common anions at sub-ppm level
      with a 10 nL injection volume. Additionally, on-column detection allowed
      visualisation of the development of the separation at any point in time and
      evaluation of the longitudinal uniformity of the ion-exchange coating.

PMID- 17207492
TI  - Capillary electrophoresis of the mycotoxin zearalenone using cyclodextrin
      enhanced fluorescence.
AB  - Certain of the cyclodextrins are capable of significantly enhancing the native
      fluorescence of the estrogenic mycotoxin zearalenone (ZEN). Twenty-two
      cyclodextrins (CDs) were screened for their ability to enhance the fluorescence
      of ZEN in a capillary electrophoresis-laser induced fluorescence (CE-LIF) format.
      Of the CDs that were examined heptakis (2,6-di-O-methyl)-beta-CD gave the
      greatest enhancement. The heptakis (2,6-di-O-methyl)-beta-CD was applied to the
      development of a CE-LIF method for detection of ZEN in maize. The resulting
      method was capable of detecting ZEN with a limit of quantitation of 5 ng/g maize.
      Recoveries of ZEN from maize spiked over the range from 5 ng/g to 500 ng/g
      averaged 103.1+/-8.5% (n=20). The CE-LIF method will be useful for future studies
      of ZEN in maize.

PMID- 17207493
TI  - Analysis of sugars in environmental samples by gas chromatography-mass
      spectrometry.
AB  - Many environmental samples contain complex mixtures of organic compounds with
      different sources, polarities and reactivities. This study reports a method for
      the analysis of both polar/water-soluble and apolar organic compounds in several
      kinds of environmental samples. The analytical method consists of extraction with
      a mixture of dichloromethane:methanol (2:1, v/v), silylation using BSTFA (N,O-bis
      (trimethylsilyl)trifluoroacetamide) and analysis by gas chromatography-mass
      spectrometry (GC-MS), a common device in chemical and environmental laboratories.
      Fifty individual sugar standards, including monosaccharides, sugar alcohols,
      anhydrosugars, disaccharides and trisaccharides, were analyzed for the
      determination of their fragmentation patterns and retention times. Recoveries (at
      three concentrations) and limits of detection (LOD) were determined for a
      standard mixture containing glucose (monosaccharide), sorbitol (sugar alcohol),
      levoglucosan (anhydrosugar) and sucrose (disaccharide), and they varied from 68
      to 119% and 130 to 360 ng mL(-1), respectively. The method was used for the
      analysis of aerosol particle, soil and sediment samples, and demonstrated its
      feasibility in detecting not only several important environmental sugars (e.g.,
      glucose, fructose, inositol, mannitol, sorbitol, levoglucosan, sucrose, mycose),
      but also a large range of organic compound classes from other polar components
      (e.g., dicarboxylic acids) to apolar compounds such as n-alkanes. Therefore, the
      analytical method presented here demonstrated its usefulness for a better
      understanding of sources and transport of various organic compounds in different
      environmental compartments.

PMID- 17207494
TI  - Hydrophobic interaction chromatography of proteins. II. Solution thermodynamic
      properties as a determinant of retention.
AB  - A general thermodynamic relation was derived to correlate protein solubility to
      retention in hydrophobic interaction chromatography (HIC). This relation is built
      on a thermodynamic formulation presented previously by Melander, Horvath and co
      workers in the context of the solvophobic theory, but the final result is
      independent of this model framework. The relation reflects an increase in protein
      retention in HIC under conditions that promote precipitation or crystallization,
      consistent with early descriptions of HIC. To examine the contribution of protein
      solubility to retention in HIC, isocratic elution experiments were performed with
      four different commercially available agarose media and four model proteins
      (ribonuclease A (RNA), lysozyme (LYS), myoglobin (MYO), and ovalbumin (OVA)). A
      wide variety of retention trends were observed as a function of protein,
      adsorbent type, salt type and concentration, and pH. In general, however, the
      results show that solubility, or its surrogate, the second osmotic virial
      coefficient, which reflects solution thermodynamic properties, correlates well
      with HIC retention in many cases; this includes correctly predicting reverse
      Hofmeister effects, which cannot be explained by retention models based on the
      solvophobic theory and preferential interaction theory. However, solution
      properties could not explain retention behavior under some conditions. In those
      cases, effects such as protein-surface interactions or conformational change
      could be important determinants of protein adsorption.

PMID- 17207495
TI  - Preformed precursor of microporous aluminophosphate coating on mesoporous SBA-15:
      synthesis, characterization, and catalytic property for selective O-methylation
      of catechol.
AB  - The synthesis of mesoporous SBA-15 coated with the preformed precursor of
      microporous aluminophosphate (AlPO) has been reported. The physicochemical
      properties of the coated samples were investigated by using XRD, FT-IR, N(2)
      adsorption, ICP, (29)Si MAS NMR, NH(3)-TPD and CO(2)-TPD. The characterization
      results suggest that the nanometer-scaled zeolite units are present on the wall
      surface of SBA-15, thus bringing the weak acid-base characteristics to the
      resulting mesoporous materials, and that the acid-base properties of these
      materials can be modified by the aging treatment in glycol. Moreover, vapor-phase
      O-methylation of catechol with methanol has been studied on these coated samples
      as catalysts. It is found that the coated sample bearing suitable weak acid-base
      sites exhibits the relatively high activity and selectivity to guaiacol.

PMID- 17207496
TI  - Comments on "a study of the collisional fragmentation problem using the gamma
      distribution approximation".
AB  - M. Kostoglou and A.J. Karabelas [J. Colloid Interface Sci. 303 (2006) 419-429]
      proposed using a gamma distribution approximation to study a collisional
      fragmentation problem. This approximation involved two types of integrals and the
      use of continued fraction expansions for their computation. In this Comment,
      explicit expressions are derived for computing the integrals.

PMID- 17207497
TI  - Population balance modeling of aggregation and breakage in turbulent Taylor
      Couette flow.
AB  - An experimental and computational study of aggregation and breakage processes for
      fully destabilized polystyrene latex particles under turbulent-flow conditions in
      a Taylor-Couette apparatus is presented. To monitor the aggregation and breakage
      processes, an in situ optical imaging technique was used. Consequently, a
      computational study using a population balance model was carried out to test the
      various parameters in the aggregation and breakage models. Very good agreement
      was found between the time evolution of the cluster size distribution (CSD)
      calculated with the model and that obtained from experiment. In order to
      correctly model the left-hand side of the CSD (small clusters), it was necessary
      to use a highly unsymmetric fragment-distribution function for breakage. As
      another test of the model, measurements with different solid volume fractions
      were performed. Within the range of the solid volume fractions considered here,
      the steady-state CSD was not significantly affected. In order to correctly
      capture the right-hand side of the CSD (large aggregates) at the higher solid
      volume fraction, a modified aggregation rate prefactor was used in the population
      balance model.

PMID- 17207498
TI  - Development of a multiplex RT-PCR for the simultaneous detection of three viruses
      of the honeybee (Apis mellifera L.): acute bee paralysis virus, Black queen cell
      virus and Sacbrood virus.
AB  - A single-step multiple-target (multiplex) reverse transcription-PCR (RT-PCR) was
      developed for the simultaneous detection and differentiation of three
      economically important viruses of the honeybee Apis mellifera L.: Acute bee
      paralysis virus (ABPV), Black queen cell virus (BQCV) and Sacbrood virus (SBV).
      Three compatible sets of primers, specific for each virus, were designed in
      conserved regions of the viral genomes for use in a one-step (single tube) RT-PCR
      assay. The individual RT-PCR assays and the combined multiplex assay were
      optimized for highest sensitivity and specificity. The multiplex RT-PCR assay was
      tested on field samples collected from Austrian honeybee colonies. All three
      viruses were detected, and their identity was confirmed by sequencing of the PCR
      products. The described multiplex RT-PCR proved to be an accurate tool for rapid
      simultaneous detection of ABPV, BQCV and SBV directly in honeybee specimens.

PMID- 17207499
TI  - The effects of nucleotides on MutS-DNA binding kinetics clarify the role of MutS
      ATPase activity in mismatch repair.
AB  - MutS protein initiates mismatch repair with recognition of a non-Watson-Crick
      base-pair or base insertion/deletion site in DNA, and its interactions with DNA
      are modulated by ATPase activity. Here, we present a kinetic analysis of these
      interactions, including the effects of ATP binding and hydrolysis, reported
      directly from the mismatch site by 2-aminopurine fluorescence. When free of
      nucleotides, the Thermus aquaticus MutS dimer binds a mismatch rapidly (k(ON)=3 x
      10(6) M(-1) s(-1)) and forms a stable complex with a half-life of 10 s
      (k(OFF)=0.07 s(-1)). When one or both nucleotide-binding sites on the
      MutS*mismatch complex are occupied by ATP, the complex remains fairly stable,
      with a half-life of 5-7 s (k(OFF)=0.1-0.14 s(-1)), although MutS(ATP) becomes
      incapable of (re-)binding the mismatch. When one or both nucleotide-binding sites
      on the MutS dimer are occupied by ADP, the MutS*mismatch complex forms rapidly
      (k(ON)=7.3 x 10(6) M(-1) s(-1)) and also dissociates rapidly, with a half-life of
      0.4 s (k(OFF)=1.7 s(-1)). Integration of these MutS DNA-binding kinetics with
      previously described ATPase kinetics reveals that: (a) in the absence of a
      mismatch, MutS in the ADP-bound form engages in highly dynamic interactions with
      DNA, perhaps probing base-pairs for errors; (b) in the presence of a mismatch,
      MutS stabilized in the ATP-bound form releases the mismatch slowly, perhaps
      allowing for onsite interactions with downstream repair proteins; (c) ATP-bound
      MutS then moves off the mismatch, perhaps as a mobile clamp facilitating repair
      reactions at distant sites on DNA, until ATP is hydrolyzed (or dissociates) and
      the protein turns over.

PMID- 17207500
TI  - Cerebellar peduncular myelinolysis in a patient receiving hemodialysis.
AB  - Here, we report the observation of extrapontine lesions, in addition to the
      pontine lesions previously documented in a diagnosed case of hemodialysis
      associated osmotic demyelination syndrome due to end-stage renal disease. The
      patient exhibited lesions on bilateral middle cerebellar peduncles, and had been
      receiving regular hemodialysis as treatment for end-stage renal disease. He
      presented with progressive gait disturbance and postural instability.
      Accompanying symptoms included peduncular hallucinations and mild cognitive
      dysfunction. Brain MRI revealed high signal intensity in the area of bilateral
      cerebellar peduncles on the diffusion and T2-weighted images, with a decreased
      signal intensity noted on the ADC map. The ataxic form of osmotic myelinolysis
      syndrome is quite rare. The involvement of the cerebellar peduncles in
      extrapontine myelinolysis in a patient with end stage renal disease has not, to
      our knowledge, been previously reported. Here, we describe the MRI findings and
      clinical features associated with this unique case, and include a review of the
      relevant literature.

PMID- 17207501
TI  - Diffusion-weighted imaging of intramural hematoma in vertebral artery dissection.
AB  - BACKGROUND AND PURPOSE: Dissections of the carotid and vertebral arteries can be
      detected by several imaging modalities, but there is yet no consensus on the most
      efficient and effective choice. METHODS: We performed diffusion-weighted imaging
      (DWI) in four patients with vertebral artery dissection documented with T2- and
      T1-weighted axial magnetic resonance imaging (MRI), and conventional angiography.
      Intervals from the onset of headache to evaluation ranged from one day to two
      weeks. RESULTS: All the patients showed high signal intensity within the affected
      vertebral artery on DWI. CONCLUSION: The movements of water molecules are more or
      less restricted within the clots according to the stage of thrombus formation in
      arterial dissection. Our study may provide another potential imaging method in
      the difficult task of proving arterial dissection.

PMID- 17207502
TI  - Applications of microfluidics for neuronal studies.
AB  - Microfabrication processes have changed the technology used in consumer goods,
      and have now advanced into applications in biology. Microfluidic platforms are
      microfabricated tools that are gaining popularity for studies of molecular and
      cellular biology. These platforms can allow precise control of the environment
      surrounding individual cells and they have been used to study physiologic and
      pharmacologic responses at the single-cell level. This article reviews
      microfluidic technology with emphasis on advances that could apply to the study
      of the nervous system, including architecture for isolation of axons, integrated
      electrophysiology, patterned physical and chemical substrate cues, and devices
      for the precisely controlled delivery of possible therapeutic agents such as
      trophic factors and drugs. The potential of these chips for the study of
      neurological diseases is also discussed.

PMID- 17207503
TI  - Introduced marine organisms as habitat modifiers.
AB  - Introductions of non-indigenous species (NIS) are mostly discussed through their
      impact on biodiversity. However, NIS can also act as ecosystem engineers,
      influencing the habitat itself, positively or negatively, directly or indirectly,
      which should be included when making risk assessments. Special concern should be
      given to changes in ecological services provided by the ecosystem. Physically,
      NIS may affect the substrate itself, or alter habitat architecture, indirectly
      influencing water movements, sediment accumulation, and light conditions.
      Chemical changes brought upon by NIS occur both on small and large scales, some
      having positive effects on ecosystem services, others can perturb epibionts.
      Furthermore, NIS may negatively affect natural resources, aquaculture or create
      fouling communities, all resulting in a negative impact on economics. However, if
      removed, already established NIS can be used as bioremediators, having a positive
      effect on different ecosystems. Using NIS for habitat management may be
      economically profitable, but could affect the habitat adversely.

PMID- 17207504
TI  - The effect of dietary folic acid deficiency on the cytotoxic and mutagenic
      responses to methyl methanesulfonate in wild-type and in 3-methyladenine DNA
      glycosylase-deficient Aag null mice.
AB  - Folic acid deficiency (FA-) augments DNA damage caused by alkylating agents. The
      role of DNA repair in modulating this damage was investigated in mice. Weanling
      wild-type or 3-methyladenine glycosylase (Aag) null mice were maintained on a FA-
      diet or the same diet supplemented with folic acid (FA+) for 4 weeks. They were
      then treated with methyl methanesulfonate (MMS), 100mg/kg i.p. Six weeks later,
      spleen cells were collected for assays of non-selected and 6-thioguanine (TG)
      selected cloning efficiency to measure the mutant frequency at the Hprt locus. In
      wild-type mice, there was no significant effect of either MMS treatment or folate
      dietary content on splenocyte non-selected cloning efficiency. In contrast, non
      selected cloning efficiency was significantly higher in MMS-treated Aag null mice
      than in saline treated controls (diet-gene interaction variable, p=0.04). The non
      selected cloning efficiency was significantly higher in the FA+ diet than in the
      FA- diet group after MMS treatment of Aag null mice. Mutant frequency after MMS
      treatment was significantly higher in FA- wild-type and Aag null mice and in FA+
      Aag null mice, but not in FA+ wild-type mice. For the Aag null mice, mutant
      frequency was higher in the FA+ mice than in the FA- mice after either saline or
      MMS treatment. These studies indicate that in wild-type mice treated with MMS,
      dietary folate content (FA+ or FA-) had no effect on cytotoxicity, but FA- diet
      increased DNA mutation frequency compared to FA+ diet. In Aag null mice, FA- diet
      increased the cytotoxic effects of alkylating agents but decreased the risk of
      DNA mutation.

PMID- 17207506
TI  - Catalytic implications of the higher plant ADP-glucose pyrophosphorylase large
      subunit.
AB  - ADP-glucose pyrophosphorylase, a key regulatory enzyme of starch biosynthesis, is
      composed of a pair of catalytic small subunits (SSs) and a pair of catalytically
      disabled large subunits (LSs). The N-terminal region of the LS has been known to
      be essential for the allosteric regulatory properties of the heterotetrameric
      enzyme. To gain further insight on the role of this region and the LS itself in
      enzyme function, the six proline residues found in the N-terminal region of the
      potato tuber AGPase were subjected to scanning mutagenesis. The wildtype and
      various mutant heterotetramers were expressed using our newly developed host
      vector system, purified, and their kinetic parameters assessed. While P(17)L,
      P(26)L, and P(55)L mutations only moderately affected the kinetic properties,
      P(52)L and P(66)L gave rise to significant and contrasting changes in allosteric
      properties: P(66)L enzyme displayed up-regulatory properties toward 3-PGA while
      the P(52)L enzyme had down-regulatory properties. Unlike the other mutants,
      however, various mutations at P(44) led to only moderate changes in regulatory
      properties, but had severely impaired catalytic rates, apparent substrate
      affinities, and responsiveness to metabolic effectors, indicating Pro-44 or the
      LS is essential for optimal catalysis and activation of the AGPase
      heterotetramer. The catalytic importance of the LS is further supported by
      photoaffinity labeling studies, which revealed that the LS binds ATP at the same
      efficiency as the SS. These results indicate that the LS, although considered
      having no catalytic activity, may mimic many of the catalytic events undertaken
      by the SS and, thereby, influences net catalysis of the heterotetrameric enzyme.

PMID- 17207505
TI  - Vagus nerve stimulation potentiates hippocampal LTP in freely-moving rats.
AB  - Previous studies have demonstrated that electrical stimulation of the vagus nerve
      (VNS) delivered at a moderate intensity following a learning experience enhances
      memory in laboratory rats and human subjects, while VNS at lower or higher
      intensities has little or no effect. This finding suggests that VNS may affect
      memory processes by modulating neural plasticity in brain structures associated
      with memory storage such as the hippocampus. To test this hypothesis, the present
      study investigated the modulatory effect of VNS on the development of long-term
      potentiation (LTP) in the dentate gyrus of freely-moving rats. Rats receiving 0.4
      mA VNS showed enhanced potentiation of the population spike amplitude for at
      least 24 h after tetanus relative to the sham-stimulation group. In contrast, no
      such effect was observed with 0.2 mA VNS. Stimulation at 0.8 mA had a short-term
      effect and tended to enhance early LTP, but to a lesser extent than did 0.4 mA.
      The 0.4 mA stimulation was the same intensity that was previously shown to
      enhance retention performance in an inhibitory avoidance task. These findings
      suggest that the neural mechanisms underlying the mnemonic effect of VNS may
      involve modulating synaptic plasticity in the hippocampus. These data also
      suggest that neural activity in the vagus nerve, occurring as a result of changes
      in peripheral state, is an important mechanism by which emotional experiences and
      arousal can enhance the storage of memories of those experiences.

PMID- 17207507
TI  - Conjugate hydrocyanation of 17-acetyl-11-carbomethoxygona-1,3,5(10),13(17)
      tetraenes.
AB  - The conjugate hydrocyanation of 17-acetylgona-11-carbomethoxy-1,3,5(10),13(17)
      tetraenes using diethylaluminum cyanide (Nagata reaction) is reported. This
      methodology has allowed the introduction of an angular cyano group at the C-13
      position of the steroid skeleton. Subsequent reduction of the nitrile group
      yielded various functionalized steroids. One of them, 22 bears the natural
      trans/anti/trans stereochemistry and possesses an hydroxyl and aminomethyl
      functionalities in the positions 11beta and 13beta, respectively. The
      characteristic (1)H and (13)C NMR spectroscopic features of the synthesized
      steroids are reported.

PMID- 17207508
TI  - Cyclin dependent kinase 2 and the regulation of human progesterone receptor
      activity.
AB  - The function of the S phase kinase cyclin A/Cdk2 in maintaining and regulating
      cell cycle kinetics is well established. However an alternative role in the
      regulation of progesterone receptor (PR) signaling is emerging. PR and its
      coactivators are phosphoproteins. Cyclin A/Cdk2 phosphorylates several of the PR
      phosphorylation sites in vitro and there is evidence that it participates in PR
      phosphorylation in vivo. Cyclin A/Cdk2 also functions as a PR coactivator.
      Overexpression increases PR transcriptional activity independent of PR
      phosphorylation. In the presence of hormone, cyclin A/Cdk2 is recruited to PR
      bound to DNA of target genes. Inhibition of Cdk activity prevents recruitment of
      the p160 coactivator steroid receptor coactivator-1 (SRC-1), suggesting that Cdk2
      phosphorylates SRC-1. Consistent with this finding, phosphatase treatment of SRC
      1 reduces its ability to interact with PR in vitro. Moreover, PR transcriptional
      activity is highest in S phase where cyclin A is expressed. In G1, PR activity is
      reduced and the capacity to recruit SRC-1 to a progestin responsive promoter is
      diminished. Future studies will focus on the importance of cyclin A/Cdk2
      phosphorylation of other components of the PR transcription complex, such as the
      p160 coactivator SRC-1, and the specific role of Cdk2 target sites in the
      regulation of PR activity.

PMID- 17207509
TI  - Insecticidal toxins from Photorhabdus bacteria and their potential use in
      agriculture.
AB  - Most of the insecticidal toxins used in agriculture come from a single bacterium
      Bacillus thuringiensis or 'Bt'. Here we review our work on the array of toxins
      produced by Photorhabdus and Xenorhabdus bacteria that are symbiotic with
      entomopathogenic nematodes, and discuss their potential for use in agriculture as
      alternatives to Bt. Despite the fact that both Photorhabdus and Xenorhabdus are
      introduced directly into the insect blood stream by their nematode vectors, they
      produce a range of toxins with both oral and injectable insecticidal activity.
      The toxin complexes (Tc's) are large orally active toxins that are displayed on
      the outer surface of the bacterium. They require three components (A-C) for full
      toxicity and one 'A' component has been successfully expressed in transgenic
      Arabidopsis to confer insect resistance. One such group of Tc's, the PirAB binary
      toxins, have oral activity against mosquitoes and some caterpillar pests. Their
      mode of action is not known but they show significant sequence similarity to a
      recently described neurotoxin beta-leptinotarsin-h isolated from the blood of the
      Colorado potato beetle. Other toxins such as 'makes caterpillars floppy' (Mcf)
      and proteins encoded by the 'Photorhabdus virulence cassettes' (PVCs) only show
      injectable activity. Mcf1 promotes apoptosis in a wide range of cells and appears
      to mimic mammalian BH3 domain-only proteins in the mitochondrion whereas the mode
      of action of the PVCs remains undetermined. The likely biological reasons for the
      massive functional redundancy in Photorhabdus insecticidal toxins are discussed.

PMID- 17207510
TI  - Reciprocal allelopathic responses between toxic cyanobacteria (Microcystis
      aeruginosa) and duckweed (Lemna japonica).
AB  - We examined cyanobacterial toxin production in response to direct exposure to an
      axenically cultured aquatic plant (Lemna japonica Landolt) using two toxic
      monoclonal strains of Microcystis aeruginosa Kuzing (NIES strains 103 and 107).
      The patterns of nutrient concentrations were similar between the controls and
      treatments. The exposure to toxic M. aeruginosa inhibited growth in L. japonica,
      and exposure to the aquatic plant caused an increase in microcystin (MC)
      production and inhibited growth in M. aeruginosa. The respective biomasses of M.
      aeruginosa and L. japonica differed significantly between control and treatments
      (p<0.05). Both intracellular MC and extracellular MC productions were
      significantly higher in the treatment than in the control for both strains
      (p<0.01). Increased MC production in response to direct exposure to this aquatic
      plant could be an induced defense mediated by the release of allelochemicals from
      the plant. This study revealed reciprocal allelopathic responses between
      Microcystis and Lemna, which can be applied to the management of eutrophic waters
      as well as an important information concerning strategies for recovering
      eutrophic waters.

PMID- 17207511
TI  - Rescue of the immunotherapeutic potential of a novel T cell epitope in the
      Epstein-Barr virus latent membrane protein 2.
AB  - Epstein-Barr virus (EBV)-associated tumors express a limited number of viral
      antigens but most of them express the latent membrane protein 2 (LMP2). This
      article describes a peptide derived from LMP2 (residues 396-404, designated LLL)
      as a potentially useful vaccine. This peptide could at first be defined as an
      unlikely T cell target as it could not stabilize MHC surface expression in
      transporter associated with antigen-processing (TAP)-deficient cells.
      Nevertheless, T lymphocytes reactive to LLL were detected in the peripheral blood
      of four EBV-seropositive healthy individuals. We have constructed a chimeric
      molecule in which LLL was fused to the amino-terminal end of the beta(2)
      microglobulin (beta(2)m). Autologous dendritic cells constitutively expressing
      the LLLbeta(2)m molecule were capable of expanding in vitro HLA-A2-restricted
      anti-LLL T lymphocytes from the peripheral blood of one of the donors. These T
      lymphocytes exhibited cytolytic activity against target cells expressing the
      chimeric molecules as well as against EBV-infected lymphoblastoid cells
      expressing natural LLL-MHC complexes.

PMID- 17207513
TI  - Relevance of PCDD/PCDF formation for the evaluation of POPs destruction
      technologies--review on current status and assessment gaps.
AB  - One important criterion for assessment of a POPs destruction technology is the
      potential formation of new POPs and other toxic by-products, in particular
      whether the highly toxic PCDDs/PCDFs are formed and under which operation
      conditions their formation is relevant. For incineration processes the formation
      mechanisms of PCDDs/PCDFs have been investigated thoroughly and strategies and
      technologies were developed to minimize their formation and emission. A detailed
      assessment of non-combustion technologies with respect to PCDD/PCDF formation is,
      however, lacking to date. A comparison of reaction conditions for PCDD/PCDF
      formation from precursor formation studies and actual applied conditions of a
      broad range of POPs destruction technologies in the present paper indicates that
      the operation conditions for a number of destruction technologies have the
      potential to generate high concentrations of PCDDs/PCDFs if dioxin precursors are
      present and that also PCDD/PCDF de novo formation can take place. Therefore a
      strategy and regulations for a more profound assessment and monitoring of the
      fate of PCDD/PCDF formation and emission is essential for the evaluation of POP
      destruction technologies and for a sound risk management of POPs. The present
      paper aims to provide a critical impulse in this respect, discusses the relevant
      formation pathways with respect to POPs destruction technologies and proposes a
      basic framework on how evaluations may be performed.

PMID- 17207512
TI  - Kinetic and mechanistic examinations of reductive transformation pathways of
      brominated methanes with nano-scale Fe and Ni/Fe particles.
AB  - In this study, carbon tetrabromide (CTB), bromoform (BF) and dibromomethane (DBM)
      were the target compounds investigated for their reduction kinetics and pathways
      with nano-scale Fe and Ni/Fe particles synthesized in laboratory. The BET surface
      areas of these nano-scale particles were around two orders of magnitude higher
      than that of the commercial micro-scale Fe particles. Batch reduction experiments
      were carried out with a metal loading of 2.5gl(-1) for the nano-scale particles,
      and 125gl(-1) for the commercial micro-scale Fe. The nano-scale Ni/Fe was the
      most reactive for reductive dehalogenation of the brominated methanes. The rates
      of bromide ion liberated during the reduction of the brominated methanes were
      usually higher than the disappearance rates of the parent compounds, indicating
      occurrence of concerted debromination mechanism. Analysis of the reduction
      kinetics showed that CTB and BF were mainly reduced through hydrogenolysis
      reaction, while over 76% of DBM was reduced through concerted reductive
      debromination to methane. Addition of Ni to Fe increased the specific reduction
      rates of the target compounds and reactive intermediates, but only marginally
      changed the distribution of their end products. Through comprehensive kinetic and
      mechanistic examinations of the reduction dehalogenation of various brominated
      methanes, a scheme summarizing their overall reduction pathways with the nano
      scale Fe and Ni/Fe is proposed.

PMID- 17207514
TI  - Evaluation of nitrification inhibitor 3,4-dimethyl pyrazole phosphate on nitrogen
      leaching in undisturbed soil columns.
AB  - The application of nitrogen fertilizers leads to various ecological problems such
      as nitrate leaching. The use of nitrification inhibitors (NI) as nitrate leaching
      retardants is a proposal that has been suggested for inclusion in regulations in
      many countries. In this study, the efficacy of the new NI, 3,4-dimethyl pyrazole
      phosphate (DMPP), was tested under simulated high-risk leaching situations in two
      types of undisturbed soil columns. The results showed that the accumulative
      leaching losses of soil nitrate under treatment of urea with 1.0% DMPP, from
      columns of silt loam soil and heavy clay soil, were 66.8% and 69.5% lower than
      those soil columns tested with regular urea application within the 60 days
      observation, respectively. However, the losses of ammonium leaching were
      reversely increased 9.7% and 6.7% under the former treatment than the latter one.
      Application of regular urea with 1.0% DMPP addition can reduce about 59.3%-63.1%
      of total losses of inorganic nitrogen via leaching. The application of DMPP to
      urea had stimulated the inhibition effects of DMPP on the ammonium nitrification
      process in the soil up to 60 days. It is proposed that the DMPP could be used as
      an effective NI to control inorganic N leaching losses, minimizing the risk of
      nitrate pollution in shallow groundwater.

PMID- 17207515
TI  - From mother to child: investigation of prenatal and postnatal exposure to
      persistent bioaccumulating toxicants using breast milk and placenta
      biomonitoring.
AB  - The exposure levels of placenta and paired breast milk samples to selected
      organochlorine compounds and pesticides from Danish and Finnish samples have been
      investigated. p,p'-DDE is the dominant pollutant, beta-HCH, hexachlorobenzene,
      endosulfan-I, dieldrin, oxychlordane, cis-heptachlor epoxide and p,p'-DDT being
      the other major constituents. Their concentrations are linearly correlated
      between milk and placenta in similar patterns for Danish and Finnish samples.
      Milk samples have higher levels of these pollutants than placenta on lipid base.
      However, the apparently not correlated compounds, such as alpha-HCH,
      pentachlorobenzene, pentachloroanisole and methoxychlor, are generally
      accumulated more in placenta, which may suggest a tissue specific metabolic
      activity. Thus, depending on the compound of interest, biomonitoring may be done
      in placenta only or in both matrices.

PMID- 17207516
TI  - Ground laser remote sensing measurements of a Saharan dust outbreak in Central
      Spain. Influence on PM10 concentrations in the lower and upper Spanish plateaus.
AB  - This paper presents the hourly evolution of a severe Saharan dust outbreak,
      (SDO), affecting Central Spain over July 23-24, 2004 measured with a laser remote
      sensing device at a location close to the Guadarrama mountain range foothills and
      its impact on PM10 levels (particles with an aerodynamic diameter below 10
      microm) recorded at four contrasting monitoring stations located in the upper and
      lower Spanish plateau, some 170km apart. During the period of study the Saharan
      dust layer, (SDL), presented significant hourly variability in height (3600
      1500m), depth (1500-700m) and aerosol dust loading (extinction coefficient, EC,
      0.22-1.28km(-1)). Overnight layering was generally observed whereas a well mixed
      layer prevailed in the afternoon. The (SDO) impact on the lower levels took place
      approximately 12h after the (SDL) was initially observed and triggered by a
      descending dust enriched, evidencing the important role of subsidence over the
      presence of dust in lower altitudes. During the event, PM10 levels at all the
      stations exceeded EU air quality daily mean standards, 50 microgm(-3), on 2
      4days. The maximum values ranged from 185 to 245 microgm(-3) depending on the
      monitoring station. The impact on PM10 spread from 2days in the upper plateau to
      3-4 in the lower plateau, in agreement with the geographical location of the
      monitoring stations with respect to the southwest origin of the intrusion. The
      impact was even more dramatic on PM10 hourly concentrations, leading to maximum
      hourly peaks ranging from 322 to 598 microgm(-3) again depending on the
      monitoring station. Correlations between EC vertical profiles and PM10 hourly
      concentrations at the monitoring stations showed the great influence of the (SDO)
      on surface concentrations. The best linear fits corresponded to the extinction
      coefficients in the lower altitudes (close to the lower range of the device 500
      650m), EC2, yielding satisfactory correlation coefficients ranging from 0.68 to
      0.71. The low variability of the slope of each individual linear fit, 19.2%,
      shows the similar impact of (SDO) on the PM10 hourly concentrations recorded in
      the area under study.

PMID- 17207517
TI  - The historical record of PCB and PCDD/F deposition at Greifensee, a lake of the
      Swiss plateau, between 1848 and 1999.
AB  - Dated sediment cores provide an excellent way to investigate the historical input
      of persistent organic pollutants into the environment and to identify possible
      sources of pollution. The vertical distribution of polychlorinated dibenzo-p
      dioxins/polychlorinated dibenzofurans (PCDD/F) and polychlorinated biphenyls
      (PCB) was investigated in a sediment core from Greifensee to elucidate the
      historical trends of PCDD/F and PCB inputs between 1848 and 1999. Concentrations
      of PCB and PCDD/F increased by more than one order of magnitude between 1930 and
      1960. PCB and PCDD/F concentrations were 5700 ng/kg dry weight (dw) and 160 ng/kg
      dw, respectively, in sediments originating from the late 1930s and reached a
      maximum of 130,000 ng/kg dw and 2400 ng/kg dw, respectively, in the early 1960s.
      From 1960 on, concentrations decreased to the 1930s level by the mid 1980s. A
      remarkable shift in the PCDD/F pattern was observed after the early 1940s. Before
      1940, the PCDD/F pattern was PCDF dominated (ratio of PCDD to PCDF=0.41+/-0.11),
      while the PCDD started to be the major species after the early 1940s (ratio of
      PCDD to PCDF=1.46+/-0.38). The temporal trends of PCB and PCDD/F correlate
      surprisingly well with each other. This might be due to the coincidence of two
      factors. The introduction of PCB on the market in the 1930s resulted in emissions
      due to the widespread use of these industrial chemicals. In the same time period,
      waste incineration became an increasingly popular way to get rid of garbage,
      boosting the PCDD/F emissions significantly. The rapid decline of PCDD/F and PCB
      concentrations in the sediment starting in the early 1960s reflects the result of
      better emission control techniques in thermal processes and the improvement of
      waste water treatment in the catchment of Greifensee.

PMID- 17207518
TI  - Polychlorinated biphenyls and -naphthalenes in pine needles and soil from Poland-
      concentrations and patterns in view of long-term environmental monitoring.
AB  - Pine needles were selected as cost effective and easy collectable matrices
      suitable for long-term monitoring of the lower troposphere pollution with
      polychlorinated biphenyls and polychlorinated naphthalenes. The fingerprints of
      PCNs and PCBs in the top layers of agricultural soils were used for determination
      of point sources of pollution for terrestrial ecosystems. The new idea based on
      the use of nona- and decachlorinated isomers fingerprint as an additional tool
      suitable for the identification of potential point sources of pollution with
      PCBs, seemed to be a capable tool to identify contamination of soil and ambient
      air related to former manufacturing and the use of highly chlorinated technical
      PCB preparations.

PMID- 17207520
TI  - Uptake of Cd, Zn and Mn by willow increases during terrestrialisation of
      initially ponded polluted sediments.
AB  - Metal concentration of plants growing on contaminated soils among other factors
      may depend on changes in the hydrological regime of the soil. Foliar and stem
      metal concentrations in Salix cinerea (grey sallow) were measured in 2
      consecutive growing seasons on a submerged sediment-derived soil that underwent
      gradual terrestrialisation. Foliar and stem cutting concentrations for Cd, Zn and
      Mn increased on plots that were submerged during the first year, but emerged in
      the second year of monitoring. The litter layer was sampled under the shrubs of a
      plot with a recent abrupt change in hydrological regime and on the reference
      plot. It was separated in three size fractions through sieving. Analysis of the
      litter fractions suggested that Cd and Zn concentrations remained constant during
      fragmentation. However, Cr, Cu, Ni and Pb concentrations increased, which was
      attributed to adhesion of mineral soil particles on the fine fraction. After
      correction for the metal content in the mineral fraction, an increase in Cd, Mn
      and Cu concentration during fragmentation of the organic part of the litter layer
      was observed for the polluted plot. Net litter layer decomposition rate was low,
      which may indicate low colonisation by the decomposing community.
      Terrestrialisation resulted in higher Cd, Mn and Zn uptake by willows. The
      deviant litter layer metal concentrations for Cd, Zn and Mn and low decomposition
      rate must be further monitored. Feasibility of measures aiming at re-establishing
      wetland conditions for the dredged sediment landfill must be considered.

PMID- 17207519
TI  - Low-carbon energy policy and ambient air pollution in Shanghai, China: a health
      based economic assessment.
AB  - Energy and related health issues are of growing concern worldwide today. To
      investigate the potential public health and economic impact of ambient air
      pollution under various low-carbon energy scenarios in Shanghai, we estimated the
      exposure level of Shanghai residents to air pollution under various planned
      scenarios, and assessed the public health impact using concentration-response
      functions derived from available epidemiologic studies. We then estimated the
      corresponding economic values of the health effects based on unit values for each
      health outcome. Our results show that ambient air pollution in relation to low
      carbon energy scenarios could have a significant impact on the future health
      status of Shanghai residents, both in physical and monetary terms. Compared with
      the base case scenario, implementation of various low-carbon energy scenarios
      could prevent 2804-8249 and 9870-23,100 PM10-related avoidable deaths (mid-value)
      in 2010 and 2020, respectively. It could also decrease incidence of several
      relevant diseases. The corresponding economic benefits could reach 507.31-1492.33
      and 2642.45-6192.11 million U.S. dollars (mid-value) in 2010 and 2020,
      respectively. These findings illustrate that a low-carbon energy policy will not
      only decrease the emission of greenhouse gases, but also play an active role in
      the reduction of air pollutant emissions, improvement of air quality, and
      promotion of public health. Our estimates can provide useful information to local
      decision-makers for further cost-benefit analysis.

PMID- 17207521
TI  - Intestinal involvement secondary to the antiphospholipid syndrome (APS): clinical
      and immunologic characteristics of 97 patients: comparison of classic and
      catastrophic APS.
AB  - OBJECTIVE: To analyze the clinical and laboratory characteristics of 97 patients
      with intestinal involvement secondary to the antiphospholipid syndrome (APS) (37
      patients with classic APS and 60 with catastrophic APS). METHODS: A computer
      assisted (PubMed) search of the literature was performed to identify all cases of
      intestinal involvement associated with the APS from 1983 to December 2005. In
      addition, we analyzed the web-site-based international registry of patients with
      catastrophic APS ("CAPS Registry"). RESULTS: There were no differences in
      distribution by gender, mean age, and previous clinical manifestations of APS
      between the 2 groups. The prevalence of abdominal pain as the presenting
      manifestation of intestinal ischemia was higher in patients with classic APS (76%
      versus 37%; P < 0.005). The main difference in histopathologic findings between
      the 2 groups was the higher rate of microthrombosis in patients with catastrophic
      APS (75% versus 4%; P < 0.0005). The mortality rate was higher in patients with
      catastrophic APS (55% versus 17%; P < 0.0005). Follow-up was available in 22
      patients with classical APS: 17 of them were discharged on oral anticoagulation
      and with a mean follow-up of 13 months (range, 1 to 48); all were in good health
      without the development of new thrombotic events. CONCLUSIONS: Intestinal
      involvement, although infrequent, is an important complication in patients with
      APS, especially in those with catastrophic APS. This would support the need for
      systematic screening for aPL in all cases of mesenteric thrombosis or ischemic
      colitis without clear underlying predisposing factors, and for systematic
      screening procedures in all classic APS patients complaining of abdominal pain.

PMID- 17207522
TI  - Optimal duration of antibiotic therapy in vertebral osteomyelitis.
AB  - OBJECTIVES: To compare the risk of relapse of vertebral osteomyelitis (VO),
      according to the duration of antibiotic therapy (< or =6 weeks versus >6 weeks).
      METHODS: We performed a 10-year retrospective study to assess the risk of VO
      relapse and to verify that this risk was not enhanced in patients who received 6
      weeks of antibiotic therapy (Group 1) as compared with those who received a
      longer treatment (Group 2). VO was diagnosed based on clinical manifestations,
      magnetic resonance imaging and/or computed tomography findings, and isolation of
      a pyogenic organism in blood cultures and/or a discovertebral biopsy. Relapse was
      diagnosed based on isolation of the same organism in blood cultures and/or a
      discovertebral biopsy. Outcome was evaluated 6 months post-treatment and in
      December 2004. RESULTS: Group 1 included 36 patients (mean age, 58 +/- 15 years)
      and Group 2 included 84 patients (mean age, 67 +/- 15 years) (P = 0.003).
      Clinical data and microorganisms were comparable in the 2 groups. In the first 6
      months, 6 (5%) patients died (Group 1, n = 2; Group 2, n = 4), and 5 (4%) in
      Group 2 relapsed, 2 with recurrent VO and 3 with recurrent bacteremia. In 2004,
      91 patients were evaluated (mean follow-up, 40.6 +/- 31 months): 77 (85%) were
      cured, 13 (14%) died (Group 1, n = 3; Group 2, n = 10), 1 had VO due to a
      different microorganism (Group 2), and no long-term relapses occurred.
      CONCLUSION: Our results suggest that antibiotic therapy of VO could be safely
      shortened to 6 weeks without enhancing the risk of relapse.

PMID- 17207523
TI  - A possible mechanism for anxiolytic and antidepressant effects of alpha- and beta
      amyrin from Protium heptaphyllum (Aubl.) March.
AB  - In the present study, we examined the anxiolytic and antidepressant effects of
      the mixture of alpha- and beta-amyrin (AMY), pentacyclic triterpenes isolated
      from the stem bark resin of Protium heptaphyllum. These effects of AMY were
      demonstrated by the open-field, elevated-plus-maze, rota rod, forced swimming,
      and pentobarbital-induced sleeping time tests, in mice. In the open-field test,
      AMY at the doses of 10, 25 and 50 mg/kg, after intraperitoneal or oral
      administrations, significantly decreased the number of crossings, grooming, and
      rearing. All these effects were reversed by the pre-treatment with flumazenil
      (2.5 mg/kg, i.p.), similarly to those observed with diazepam used as a positive
      standard. In the elevated-plus-maze test, AMY increased the time of permanence
      and the number of entrances in the open arms. On the contrary, the time of
      permanence and the number of entrances in the closed arms were decreased. All
      these effects were also completely reversed by flumazenil, an antagonist of
      benzodiazepine receptors. In the pentobarbital-induced sleeping time test, AMY at
      the same doses significantly increased the animals sleeping time duration. In the
      rota rod test, AMY did not alter motor coordination and, thus, was devoid of
      effects, as related to controls. Since AMY, at the doses of 10 and 25 mg/kg,
      showed a sedative effect in the open field test, lower doses (2.5 and 5.0 mg/kg)
      were used in the forced swimming test, producing a decrease in the immobility
      time, similarly to that of imipramine, the positive control. The effect of AMI
      was greater when it was administered 15 min after imipramine (10 mg/kg). However,
      the antidepressant AMY effects were not altered by the previous administration of
      paroxetine, a selective blocker of serotonin uptake. In addition, AMY effects in
      the forced swimming test were totally blocked by reserpine pretreatment, a drug
      known to induce depletion of biogenic amines. In conclusion, the present work
      evidenced sedative and anxiolytic effects of AMY that might involve an action on
      benzodiazepine-type receptors, and also an antidepressant effect where
      noradrenergic mechanisms will probably play a role.

PMID- 17207524
TI  - Dependence potential of nicotine replacement treatments: effects of product type,
      patient characteristics, and cost to user.
AB  - OBJECTIVE: To assess the extent of long-term use of different nicotine
      replacement treatment products in smokers attending routine smoking cessation
      treatment and to examine the effect of nicotine replacement treatment cost on its
      long-term use. METHOD: 1518 consecutive patients prescribed nicotine replacement
      treatment at the East London Smokers' Clinic between January 2000 and November
      2002 were followed up at 1-year. RESULTS: The rates of long-term use ranged from
      2% for patch to 13% for nasal spray. Long-term use of nicotine replacement
      treatment was significantly more likely in more dependent smokers. Treatment
      cost, and whether it was provided free of charge, had no significant effect on
      its long-term use. CONCLUSIONS: Long-term use of nicotine replacement treatment
      is not uncommon. Its occurrence seems positively related to speed of nicotine
      delivery of individual products. For self-selected highly dependent smokers, long
      term use of nicotine replacement treatment may be a necessary precondition for
      maintaining long-term abstinence. The findings have financial and clinical
      implications for providers of smoking cessation services.

PMID- 17207525
TI  - Laser-induced fluorescence to discriminate between a dental composite resin and
      tooth.
AB  - PURPOSE: Investigation of laser-induced fluorescence of an experimental pigment
      (Flu) to discriminate between a filling and the tooth and its influence on the
      material properties of experimental dental composites. MATERIALS AND METHODS:
      Three experimental composites (EC) were manufactured. The standard contained no
      Flu, Flu-0.5 contained 0.5%, Flu-1.0 contained 1%. To judge the extent of
      fluorescence, specimens and fillings placed in natural teeth were irradiated with
      an infrared laser (980 nm, 120 mW). Flexural strength, modulus of elasticity,
      depth of cure, water sorption, solubility, and color (CIE-L(*)a(*)b(*)-values)
      were measured to investigate the influence of Flu on EC. ANOVA was calculated and
      the statistical significance was p < 0.05. RESULTS: Strong laser-induced green
      fluorescence was observed so that fillings and tooth structures were clearly
      discriminated. No influence of Flu on flexural strength and modulus of elasticity
      occurred. Water sorption and solubility were far below the limits of EN ISO 4049.
      Increasing Flu concentrations revealed minor but significant reduction of depth
      of cure, shifts to more white and red and less yellow. SIGNIFICANCE: Flu provides
      laser-induced fluorescence allowing an easy discrimination between fillings and
      teeth. Flu did not severely influence the material properties.

PMID- 17207526
TI  - Light transmission through porcelain.
AB  - OBJECTIVE: This study evaluates the effect of shade and thickness of porcelain in
      light transmission. METHODS: One hundred and twenty-eight disks of Duceram
      porcelain were made to combine four different thicknesses (1.5; 2.0; 3.0; 4.0 mm)
      and eight shades (A(1); A(4); B(1); B(4); C(1); C(4); D(2); D(4)). A digital
      power meter (Newport Optical Power Meter was used to measure light transmission.
      The porcelain transmission coefficient was calculated using Lambert-Beer law,
      t(c)=Ce(-alphad), where t(c) is the transmission coefficient, C the contribution
      factor of the reflection coefficient, e a constant, alpha the absorption
      coefficient and d is the sample thickness. RESULTS: The transmission coefficients
      did not vary statistically in relation to the two visible light-curing units
      studied. From all the samples, the colors A(1) and D(2), thickness 1.5 mm,
      presented the highest percentages of transmission (8%) and the shades, A(4), B(4)
      and C(4), thickness 4 mm, the lowest (0.5%). The relationship between the
      Naperian logarithm of the transmission coefficient and the samples thickness
      followed the Lambert-Beer law. The linear adjustment of the experimental points
      of the two variables, showed the absorption coefficient (alpha) and the constant
      value related to the reflection (C) of each porcelain shade. The reflection
      coefficient values of all shades did not vary statistically among themselves.
      SIGNIFICANCE: For most shades there was a significant decrease in light
      transmission as the sample porcelain thickness increased. For the same thickness
      most shades presented statistical difference between the transmission
      coefficients. However, the larger the thickness, the higher the number of shades
      which, statistically, showed no difference.

PMID- 17207527
TI  - Gene expression analysis identifies a genetic signature potentially associated
      with response to alpha-IFN in chronic phase CML patients.
AB  - Microarray-based gene expression analysis was performed on diagnostic chronic
      phase CML patient samples prior to interferon treatment. Fifteen patient samples
      corresponding to six cytogenetic responders and nine non-responders were
      included. Genes differentially expressed between responder and non-responder
      patients were listed and a subsequent leave-one-out cross validation (LOOV)
      procedure showed that the top 20 genes allowed the highest prediction accuracy.
      The relevant genes were quantified by real-time PCR that supported the microarray
      results. We conclude that it might be possible to use gene expression analysis to
      predict future response to interferon in CML diagnostic samples.

PMID- 17207528
TI  - Effects of hydroxy-polychlorinated biphenyl (OH-PCB) congeners on the xenobiotic
      biotransformation gene expression patterns in primary culture of Atlantic salmon
      (Salmo salar) hepatocytes.
AB  - Hydroxylated metabolites of PCBs [OH-PCBs] represent new health and environmental
      concern because they have been shown to have agonist or antagonist interactions
      with hormone receptors (HRs) or hormone-receptor mediated responses. The present
      study was designed to investigate the estrogenic potency based on anti-AhR
      signalling effect of three 4-OH substituted PCB congeners (#107, #146 and #187),
      one 3-OH substituted congener (#138), and the pharmaceutical synthetic estrogen,
      ethynylestradiol (EE2) in fish in vitro system using primary culture of Atlantic
      salmon hepatocytes. The effects were studied by quantifying changes in
      transcripts with gene-sequence primer pairs for a suite of gene responses
      (AhRalpha, ARNT, CYP1A1, CYP3A, UGT and GST) belonging to the xenobiotic
      biotransformation system. Our data show that OH-PCB congeners and EE2, decreased
      AhRalpha and ARNT transcript levels, and CYP1A1, UGT and GST gene expressions,
      together with CYP3A gene expression. The decreased expression of transcripts for
      xenobiotic biotransformation system is related to the concentration of individual
      OH-PCB congener and these responses are typical of reported estrogenic and
      estrogen-like effects on the CYP system. Modulation of biotransformation pathways
      by OH-PCBs may alter xenobiotic metabolism leading to the production of toxic
      reactive molecules, altering pharmacokinetics and diminishing the clearance rate
      of individual chemicals from the organism.

PMID- 17207529
TI  - Genetic study of familial uveal melanoma: association of uveal and cutaneous
      melanoma with cutaneous and ocular nevi.
AB  - PURPOSE: To evaluate a kindred with familial uveal and cutaneous melanoma and to
      identify potential genetic and environmental factors that may predispose
      individuals to develop uveal melanoma. DESIGN: Family-based case report with
      detailed clinical and genetic evaluation. PARTICIPANTS: Ten siblings in a single
      nuclear family. METHODS: Evaluation of a large sibship via family history,
      complete eye and skin examinations, environmental risk factor questionnaire, and
      genetic testing, as well as a MEDLINE search of familial uveal melanoma kindreds.
      MAIN OUTCOME MEASURES: Cutaneous and ocular nevi, benign and malignant neoplasms
      of skin and other sites, brief skin cancer risk assessment tool risk
      classification for cutaneous melanoma, DNA sequencing of p16INK4a and p14ARF
      genes, and citations on familial uveal melanoma. RESULTS: The proband and his
      mother had uveal melanoma, 3 cutaneous melanomas occurred among 2 siblings, and 2
      other siblings had basal cell carcinomas. No germline mutations were detected in
      the melanoma-associated tumor suppressor genes p16INK4a and p14ARF. Seven out of
      10 siblings had a history of cutaneous and/or ocular nevi. Of the 3 subjects
      without nevi, 2 had histories of eye or skin malignancies (1 uveal melanoma, 1
      basal cell carcinoma). Three of the 10 siblings had relevant ocular findings (2
      choroidal nevi, 1 uveal melanoma). Six were also found to be in the "high-risk"
      classification for cutaneous malignancies based on scores from a previously
      validated risk assessment tool. This family, combined with the 91 previously
      reported familial uveal melanoma kindreds, brings to 92 the total number thus far
      recorded. CONCLUSIONS: Our results strengthen the association between uveal
      melanoma, atypical nevi, and cutaneous melanoma. This relationship supports the
      recommendation that individuals with a personal or family history of uveal
      melanoma, particularly in combination with atypical nevi, should be regularly
      screened for uveal and cutaneous melanoma.

PMID- 17207530
TI  - Spontaneous reattachment of rhegmatogenous retinal detachment.
AB  - PURPOSE: To describe the clinical characteristics of spontaneous reattachment of
      rhegmatogenous retinal detachment (SRRRD). DESIGN: Retrospective observational
      case series. PARTICIPANTS: Fifteen patients who were diagnosed with SRRRD.
      METHODS: The medical records of 15 patients were reviewed. Spontaneous
      reattachment of rhegmatogenous retinal detachment was confirmed via serial
      observation in 4 of the eyes, and the remaining eyes represented patients in whom
      the condition was presumed to develop. MAIN OUTCOME MEASURES: Clinical features
      and association. RESULTS: This study involved 6 male patients and 9 female
      patients with a mean age of 48.0 years. The mean refractive errors in the
      involved and contralateral eyes were -5.0 and -5.3 diopters, respectively. All 15
      eyes evidenced diffuse retinal pigmentary alterations within a sharply demarcated
      and convex margin. The lesions were located in the inferior retina in 10 of the
      15 eyes, limited to 6 clock hours or fewer (66.7%). Although subretinal gliotic
      bands were detected within the lesion in 11 patients (73.3%), epiretinal
      proliferation was evident in only 2 patients (13.3%). Retinal changes associated
      with rhegmatogenous retinal detachment were noted in the fellow eyes of 7
      patients (46.7%). CONCLUSIONS: Spontaneous reattachment of rhegmatogenous retinal
      detachment should be included in differential diagnoses of patients with diffuse
      retinal pigmentary alterations within a sharply demarcated convex margin in
      unilateral eyes. Small retinal breaks observed in nonvitrectomized eyes may be
      associated with the occurrence of SRRRD.

PMID- 17207531
TI  - Corneal endotheliitis associated with evidence of cytomegalovirus infection.
AB  - OBJECTIVE: To describe the clinical presentation of cytomegalovirus (CMV) corneal
      endotheliitis in human immunodeficiency virus (HIV)-negative patients. DESIGN:
      Retrospective interventional case series. PARTICIPANTS: Twelve consecutive
      patients with corneal endotheliitis diagnosed between 2002 and 2005. METHODS:
      Aqueous of eyes with corneal endotheliitis was analyzed for viral DNA by
      polymerase chain reaction (PCR), and patient records were reviewed for
      demographic data, medical and ocular history, best-corrected Snellen visual
      acuity, intraocular pressure (IOP), anterior and posterior segment findings,
      laboratory workup, diagnosis, and treatment. MAIN OUTCOME MEASURE: Presence of
      CMV DNA. RESULTS: Corneal endotheliitis was seen in 12 eyes of 10 patients during
      the study period. There were 8 men and 2 women, and all were Chinese. Their mean
      age was 49 years (range, 25-61 years). The corneal involvement ranged from small
      areas of focal endotheliitis to diffuse bullous keratopathy. The keratic
      precipitates had a variable appearance. There was only mild anterior chamber
      inflammation with no posterior synechiae. Two thirds of eyes had diffuse iris
      atrophy. All the eyes had elevated IOP. Eleven of the 12 eyes were positive for
      CMV DNA. None of the patients were positive for HIV. All patients had received
      local or systemic immunosuppression, or both, before corneal endotheliitis
      developed. Ten eyes of 8 patients were treated with systemic antiviral therapy.
      After treatment, the endotheliitis resolved completely in 7 eyes, and 3 eyes had
      significant improvement in corneal translucency. The IOP was normal, with no
      medications in all but 1 eye. Repeat PCR analysis in all the treated eyes was
      negative for CMV DNA. CONCLUSIONS: Cytomegalovirus infection is an important
      cause of corneal endotheliitis in our patients, and appropriate antiviral therapy
      may prevent more ocular damage.

PMID- 17207532
TI  - Differential reactivity of alpha and beta 2'-deoxyribonucleosides towards
      protonation and metalation.
AB  - The reactivity of artificial 2'-deoxyribonucleosides, designed as nucleoside
      surrogates in metal-mediated base pairs, towards protonation and metalation has
      been shown to be dependent on the choice of the anomer. The alpha nucleosides
      comprising the aglycones imidazole, 1,2,4-triazole, benzimidazole and imidazo[4,5
      b]pyridine are more basic than the respective beta nucleosides as was shown by a
      combined experimental and theoretical approach. The DeltapK(a) values observed
      experimentally are in the range of 0.19+/-0.03 to 0.41+/-0.07 (with the error
      representing three times the standard deviation of the mean value). An
      independent confirmation of this differential reactivity was obtained from
      density functional theory (DFT) calculations using 1,2,4-triazole nucleoside as
      an example. The result of these calculations is in good agreement with the
      experimental data (DeltapK(a)=0.16 vs. 0.21+/-0.07). The stability of the
      respective metal ion complexes of the anomeric 1,2,4-triazole nucleosides follows
      the same trend as that of the respective protonated nucleosides: Those of the
      alpha nucleoside are more stable than those of the beta nucleoside
      (Deltalogbeta(2)=0.6+/-0.2 for the 2:1 complex with Ag(+); Deltalogbeta(1)=0.51+/
      0.07 for the 1:1 complex with Hg(2+)). These slightly different reactivities will
      be useful for fine-tuning the metal-ion binding behavior of oligonucleotides
      containing metal-mediated base pairs.

PMID- 17207533
TI  - Intracellular osmotic gradient generation in rat ventricle myocyte by using a
      micro-perfusion system.
AB  - This experimental study describes the fabrication and analysis of a micro
      perfusion system that can be used in many bioengineering experiments to create
      rapid, large regional intracellular changes within single ventricular myocytes.
      The myocyte was a kind of osmometer since the cell volume was found to be
      strongly dependent on the perfusion solution osmolarity. This volume change was
      measured, indirectly, by measuring the cell width change using video-microscopy
      and image analysis software. Jacob's equation was used to model these results
      successfully. Some dual perfusion experiments to see the effects of the localized
      perfusion of different osmotic solutions to generate an osmotic gradient inside
      myocytes were also investigated. This device can be useful for studying the
      effects of localized pH or osmotic gradients inside myocytes, estimating
      intracellular ion diffusion rates, and inducing regional changes in other
      important intracellular ions.

PMID- 17207534
TI  - Hydroxymethyl methacrylate-based monolithic columns designed for separation of
      oligonucleotides in hydrophilic-interaction capillary liquid chromatography.
AB  - Hydroxymethyl methacrylate-based monolithic columns for separation of
      oligonucleotides by capillary liquid chromatography (CLC) were prepared. We
      optimized composition of the polymerization mixture, which contained the monomer
      mixture consisting of N-(hydroxymethyl) methacrylamide (HMMAA) and ethylene
      dimethacrylate (EDMA), and the porogenic system composed of propane-1-ol, butane
      1,4-diol and alpha, alpha'-azoisobutyronitrile (AIBN) as initiator. Separations
      of oligonucleotides were performed in HILIC (hydrophilic-interaction) mode using
      100 mM triethylamine acetate (TEAA) in acetonitrile and in water as eluents. The
      influence of steepness of the mobile phase gradient on separation of the
      oligonucleotides was evaluated as well as the reproducibility of HMMAA monolith
      preparation.

PMID- 17207535
TI  - A novel monoclonal antibody specific for the amino-truncated beta-amyloid Abeta5
      40/42 produced from caspase-cleaved amyloid precursor protein.
AB  - Deposition of beta-amyloid peptide (Abeta) as senile plaques and amyloid
      angiopathy are the major neuropathological features of Alzheimer's disease (AD).
      Heterogeneity is observed in the N- and C-termini of the deposited Abeta species.
      Recent evidence implicates caspase activation and apoptosis in AD
      neurodegeneration. We previously reported that a distinct N-terminally truncated
      Abeta species, Abeta5-40/42 is preferentially produced from the caspase-cleaved
      form of amyloid precursor protein (APP) lacking its C-terminal 31 amino acids and
      that it is deposited in AD brain tissues. Here, we generated a novel monoclonal
      antibody specific to the N-terminal end of Abeta5-40/42. Western blotting
      confirmed that this antibody recognizes Abeta5-40 but not Abeta1-40. We also
      showed that the antibody is able to immunoprecipitate Abeta5-40 but not Abeta1
      40. Immunoprecipitation with the antibody followed by mass spectrometric analysis
      further detected Abeta5-40 in the conditioned media from neuroblastoma cells
      expressing the caspase-cleaved APP. The antibody reacted weakly with Abeta
      derived from AD brains. These results suggest that our novel monoclonal antibody
      is useful for detecting the N-terminally truncated Abeta produced in conjunction
      with caspase activation.

PMID- 17207536
TI  - An electrophysiological endophenotype of hypomanic and hyperthymic personality.
AB  - BACKGROUND: Hyperthymic Temperament (HYT) and a closely related trait, Hypomanic
      Personality (HYP), have both been related to bipolar affective disorder (BAD).
      Intensity dependence of auditory evoked potentials (IAEP) is a suggested inverse
      indicator of serotonergic neurotransmission and has been found to be elevated in
      BAD. Therefore the present study explored for the first time whether subclinical
      variance of HYT/HYP is also associated with IAEP in a healthy sample. As several
      traits from biological personality research are correlated with HYT/HYP and also
      with BAD, the specificity of results against these traits was further analyzed by
      calculating multiple regression analyses. METHODS: Evoked potentials were
      recorded from a sample (N=87) homogenous for confounding variables influencing
      IAEP. For this reason, only 19 to 27-year-old non-smoker psychiatrically healthy
      male students were included. RESULTS: Significant correlations were found between
      IAEP and both HYP and HYT. Including Sensation or Novelty Seeking and
      Extraversion in Regression Analyses did not weaken the associations of HYP with
      IAEP much, but did affect those of HYT. However, these competing biological
      personality traits were hardly able to predict IAEP themselves. Impulsivity,
      though, was able to reduce the predictive power of HYP and HYT and to explain
      unique IAEP-variance. This was even more the case for Behavioral-Activation
      System-Sensitivity (BAS) subscale Fun Seeking clearly dominating all regression
      analyses. LIMITATIONS: Homogeneity of sample. CONCLUSIONS: The impact of BAS is
      in agreement with the assumption that heightened BAS-sensitivity is an underlying
      biological cause for HYP/HYT and for BAD. Future studies on BAD should include
      BAS and Impulsivity besides HYP/HYT to further explore uniqueness of the latter
      and to develop questionnaires based on those items of a hyperthymic-hypomanic
      impulsive-funseeking item pool, which possess the most external validity.

PMID- 17207537
TI  - Induction of local and systemic immune reactions following infection of turkeys
      with avian Metapneumovirus (aMPV) subtypes A and B.
AB  - Most of the studies regarding the immunopathogenesis of avian Metapneumovirus
      (aMPV) have been done with subtype C of aMPV. Not much is known about the
      immunopathogenesis of aMPV subtypes A and B in turkeys. Specifically, local
      immune reactions have not been investigated yet. We conducted two experiments in
      commercial turkeys. We investigated local and systemic humoral and cell mediated
      immune reactions following infection with an attenuated vaccine strain of aMPV
      subtype B (Experiment I) and virulent strains of aMPV subtypes A and B
      (Experiment II). Turkeys infected with virulent aMPV strains developed mild
      respiratory signs while birds inoculated with the attenuated aMPV did not show
      any clinical signs. Virus neutralizing antibodies were detected locally in
      tracheal washes and systemically in serum as soon as 5-7 days post aMPV infection
      (PI) independent of the strain used. Virus neutralizing antibody titres peaked at
      7 days PI and then antibody levels declined. The peak of serum ELISA antibody
      production varied between infected groups and ranged from 14 and 28 days PI. All
      aMPV strains induced an increase in the percentage of CD4+ T cell populations in
      spleen and Harderian gland at days 7 or 14 PI. Furthermore, as shown in
      Experiment I, infection with the attenuated aMPV-B strain stimulated spleen
      leukocytes to release significantly higher levels of interferons (IFNs),
      interleukin-6 and nitric oxide in ex vivo culture in comparison to virus-free
      controls up to 7 days PI (P<0.05). As detected by quantitative real time RT-PCR
      in Experiment II, infection with virulent aMPV induced an increased IFNgamma
      expression in the Harderian gland in comparison to virus-free controls. IFNgamma
      expression in the spleen varied between aMPV strains and days PI. Overall, our
      study demonstrates that aMPV subtypes A and B infection induced humoral and cell
      mediated immune reactions comparable to subtype C infections. We observed only
      temporary stimulation of serum virus neutralizing antibodies and of most of the
      local immune reactions independent of the aMPV strain used. The temporary
      character of immune reactions may explain the short duration of protection
      against challenge following aMPV vaccination in the field.

PMID- 17207538
TI  - Protein kinase C-zeta mediates retinal degeneration in response to TNF.
AB  - Tumor necrosis factor-alpha (TNF) has been implicated in retinal ganglion cells
      (RGC) degeneration in glaucoma. Atypical protein kinase C (PKC) zeta is involved
      in cell protection against various stresses. The aim of this study was to
      investigate the potential proapoptotic effects of intravitreal injections of TNF
      with or without PKCzeta specific inhibitor on the rat retina. TNF was injected in
      the vitreous of rat eyes alone or in combination with specific PKCzeta inhibitor.
      PKCzeta and NF-kappaB were studied by immunohistochemistry and western-blotting
      analysis on retina, and apoptosis quantified by the TUNEL assay. While low basal
      PKCzeta was observed in the control eyes, TNF induced intense expression of
      PKCzeta mostly in bipolar cells processes. PKCzeta staining became nuclear when
      TNF was coinjected with PKCzeta inhibitor. TNF alone did not induce apoptosis in
      the retina. Coinjection of the PKCzeta-specific inhibitor and TNF, however,
      induced apoptosis in the inner nuclear and ganglion cell layers. The PKCzeta
      specific inhibitor unmasks retinal cells to TNF cytotoxicity showing a link
      between the proapoptotic effects of TNF and the antiapoptotic PKCzeta signaling
      pathway.

PMID- 17207539
TI  - Endoscopic transnasal repair of choanal atresia.
AB  - OBJECTIVES: To present our experience with a new endoscopic technique for
      transnasal repair of choanal atresia. METHODS: Seventeen patients aged 2 months
      to 13 years with choanal atresia, bilateral in 6 and unilateral in 11, underwent
      endoscopic repair using a mucoperichondrial flap developed from the nasal septum.
      The bony stenosis was opened with a surgical curette or drill, and the raw
      surface was covered by the flap. All patients in these case series with bilateral
      atresia had been treated with dilatation at birth and had restenosis. RESULTS: A
      total of 23 choanae were operated. Follow-up ranged from 10 to 60 months. There
      was one case of complete restenosis and one of partial restenosis, for a success
      rate of 91%. CONCLUSIONS: Endoscopic repair of choanal atresia is a safe and
      rapid procedure even in very young children, with no complications and a high
      rate of success.

PMID- 17207540
TI  - Comparison of two gel filtration chromatographic methods for the purification of
      Lily symptomless virus.
AB  - Lily symptomless virus (LSV) occurs frequently in many Lilium species worldwide
      and often causes developmental abnormalities such as a smaller flower and lower
      bulb yield. In this study, two moderate and efficient gel filtration
      chromatography (GFC) methods was compared, these two techniques were,
      respectively, based on Superdex-200 HR and Sephacryl S-1000 SF. The products
      purified by the two methods were then characterized by measurements with UV
      spectrophotometer, reverse transcriptase (RT)-PCR, transmission electron
      microscope (TEM), polyacrylamide gel electrophoresis (PAGE), Western blotting and
      matrix assisted laser desorption-ionisation/time-of-flight mass spectrometry
      (MALDI-TOF-MS). The final yield of purified LSV by the Superdex-200 HR GFC was
      9.4 mg from 50 g of fresh infected tissues of Lanzhou lily. However, from the
      same amount tissues, only 5.6 mg of LSV were obtained by using Sephacryl S-1000
      SF GFC. The Superdex-200 HR method was thus shown to be more suitable for the
      purification of LSV than the Sephacryl S-1000 SF GFC. The Superdex-200 HR method
      does not require costly equipment for density centrifugation and
      ultracentrifugation. Furthermore, it can provide an economical and efficient way
      to obtain purified products for the preparation of antibodies for serological
      diagnosis or LSV infection and related investigations.

PMID- 17207542
TI  - Nitric oxide involvement in estrous cycle-dependent changes of the behavioral
      responses of female rats in the elevated plus-maze test.
AB  - Nitric oxide (NO)/cGMP pathway is known as a mediator in anxiety modulation. In
      this study, we assessed the involvement of NO pathway in the estrous cycle
      related changes of anxiety level in rat. By using elevated plus-maze test, we
      studied the changes of serum nitrate and nitrite (NO(x)) levels in comparison to
      the estrous cycle-dependent changes of anxiety state. Then, we tested the effects
      of nitric oxide synthase (NOS) inhibitor, L-NAME (10, 60mg/kg, i.p.), and the NO
      precursor, l-arginine (100mg/kg, i.p.) on anxiety modulatory properties of
      exogenous ovarian hormones in ovariectomized (OVX) rats. Compared with other
      cycle phases and with OVX rats, cycling rats spent more time in open arms and had
      lower levels of serum NO(x) levels during metestrous while they spent less time
      in open arms and had lower levels of serum NO(x) levels during proestrous. In OVX
      rats, L-NAME (60mg/kg, i.p.) exerted anxiolytic effect while l-arginine showed no
      effect. In comparison with corn oil-treated controls, estradiol benzoate
      (10microg/kg, subcutaneously (s.c.)) significantly increased the serum NO(x)
      level and exerted anxiogenic effect, which was dose-dependently inhibited by L
      NAME but was not changed by l-arginine. In contrast, progesterone (25mg/kg, s.c.)
      significantly decreased the serum NO(x) level and exerted anxiolytic effect,
      which was abolished by l-arginine but was not affected by L-NAME. These findings
      suggest that NO system might be involved in the estrous cycle-related changes of
      anxiety level, probably by mediating the effect of ovarian sex hormones.

PMID- 17207543
TI  - Necrotic death without mitochondrial dysfunction-delayed death of cardiac
      myocytes following oxidative stress.
AB  - Oxidative stress has been implicated in cell death in range of disease states
      including ischemia/reperfusion injury of the heart and heart failure. Here we
      have investigated the mechanisms of cell death following chronic exposure of
      cardiac myocytes to oxidative stress initiated by hydrogen peroxide. This
      exposure induced a delayed form of cell death with ultrastructural changes
      typical of necrosis, and that was accompanied by the release of lactate
      dehydrogenase and increased lipid peroxidation. However, this delayed death was
      not accompanied by the loss of mitochondrial membrane potential or caspase-3
      activation. Furthermore, we could demonstrate that this delayed necrosis was at
      least partially prevented by pre-treatment with the hypertrophic stimuli
      endothelin-1 or leukemic inhibitory factor. Our results suggest that this delayed
      form necrosis may also comprise an ordered series of events involving pathways
      amenable to therapeutic modulation.

PMID- 17207541
TI  - The reach-to-grasp-food task for rats: a rare case of modularity in animal
      behavior?
AB  - Humans and non-human animals make use of sensory hierarchies in "selecting"
      strategies for solving many cognitive and behavioral tasks. Often, if a preferred
      type of sensory information is unavailable or is not useful for solving a given
      task, the animal can switch to a lower-priority strategy, making use of a
      different class of sensory information. In the case of rats performing a classic
      reach-to-grasp-food task, however, prior studies indicate that the reaching
      maneuver may be a fixed action pattern that is guided exclusively by the food's
      odor plume until the point of contact with the food morsel [Whishaw IQ, Tomie JA.
      Olfaction directs skilled forelimb reaching in the rat. Behav Brain Res
      1989;32(1):11-21; Metz GA, Whishaw IQ. Skilled reaching an action pattern:
      stability in rat (Rattus norvegicus) grasping movements as a function of changing
      food pellet size. Behav Brain Res 2000;116(2):111-22; Whishaw IQ. Did a change in
      sensory control of skilled movements stimulate the evolution of the primate
      frontal cortex? Behav Brain Res 2003;146(1/2):31-41]. We sought to confirm and
      extend these findings in several ways. In Experiment 1, using a GO/NO-GO variant
      of the classic task, we demonstrated that rats used the GO target's odor both to
      trigger and guide their reaches. In Experiment 2, we showed that rats deprived of
      (a) vision, (b) object-recognizing rostral whiskers and forearm sinus hairs, or
      (c) both, displayed no deficits in triggering and guiding their reaches. Finally,
      in a third experiment in which the GO target's location varied randomly across
      trials and only olfactory cues were available, we demonstrated that rats could
      determine the spatial endpoint of their reach without any loss of accuracy.
      Combined with results from a prior study in which bulbectomized rats never
      developed a new, successful reaching strategy despite extensive post-operative
      training [Whishaw IQ, Tomie JA. Olfaction directs skilled forelimb reaching in
      the rat. Behav Brain Res 1989;32(1):11-21], these results indicate that rats do
      not have a sensory hierarchy for solving the reach-to-grasp-food task, but
      rather, are guided by olfaction alone until their paw contacts the food morsel.

PMID- 17207544
TI  - LBT/PTD dual tagged vector for purification, cellular protein delivery and
      visualization in living cells.
AB  - Cellular protein delivery is an emerging technique, by which exogenous
      recombinant proteins are delivered into mammalian cells across the membrane. We
      have developed an E. coli expression vector suited for protein cellular delivery
      experiments. The plasmid is designed to generate a C-terminal fusion with the 12
      amino acid HIV-Tat peptide as a protein transduction domain (PTD), whereas the
      protein N-terminus is fused to an 17-residue peptide lanthanide-binding tag
      (LBT). LBT is used for both purification by affinity chromatography and
      fluorescent detection with Tb(3+) as a coordinating metal. We have employed the
      TA-cloning site between the two tags, LBT and PTD, according to the PRESAT-vector
      methodology [N. Goda, T. Tenno, H. Takasu, H. Hiroaki, M. Shirakawa, The PRESAT
      vector: asymmetric T-vector for high-throughput screening of soluble protein
      domains for structural proteomics, Protein Sci. 13 (2004) 652-658], which
      facilitates unidirectional cloning of any PCR-amplified DNA fragments
      corresponding to the protein of interest. A simple three-step protocol consisting
      of affinity purification of LBT/PTD dual-tagged proteins has also been developed,
      in which the proteins are purified by heparin-, then immobilized Ni(2+)-, and
      then heparin-affinity chromatography, in this order. The purified protein is
      ready for protein delivery experiment, and the delivered protein is visible by
      fluorescent microscopy. Our LBT/PTD dual-tagged PRESAT-vector provides a powerful
      research tool for exploring cellular functions of proteins in the post-genomic
      era.

PMID- 17207545
TI  - Assessing the effect of interventions on the risk of cattle and sheep carrying
      Escherichia coli O157:H7 to the abattoir using a stochastic model.
AB  - Escherichia coli O157:H7 persists in being a threat to food safety. The
      mechanisms behind the spread of E. coli O157:H7 on the farm are complex and
      poorly understood. The objective of this study was to apply a Monte Carlo model,
      constructed to simulate the propagation of E. coli O157:H7 in cattle and sheep on
      the farm, to both test the effect of different interventions on the risk of
      animals carrying E. coli O157:H7 to the abattoir and to develop understanding of
      the underlying processes, including the identification of areas that could
      benefit from further research. An overview of the model including key assumptions
      is given. The output statistics from batches of 100 runs of the model were
      collected. From the model output, a cumulative frequency distribution of the
      prevalence and specific shedding level for the groups of cattle or sheep being
      sent to the abattoir were generated. Stochastic dominance was used to compare the
      results of the model outputs. Using the shorthand that "risk" means the
      likelihood of carrying E. coli O157:H7 to the abattoir, key conclusions from the
      study included: mixing sheep and cattle increases the risk in both groups;
      merging groups of animals of the same species into larger groups increases the
      risk substantially; increasing stocking density increases the risk independently
      of group size; decreasing the group size decreases the E. coli O157:H7 prevalence
      independently of stocking density; a very high level of barn hygiene reduces the
      risk; a shorter time between spreading farmyard manure and grazing and an
      increased background level of E. coli O157:H7 in the model increases the risk.
      The background level could be influenced by the presence of wild animals carrying
      the organism. The parameters to which the model is most sensitive are those
      related to transmission from grass and enclosures to animals, pathogen survival
      on grass, in slurry and in barns and contact between animals.

PMID- 17207546
TI  - Multifunctional cargo systems for biotechnology.
AB  - One of the challenges in the field of bio-nanotechnology is the development of
      nano-sized delivery systems comprising different functionalities. These systems
      should carry bioactive substances to predefined site and unload them in
      controlled manner. Capsules assembled layer-by-layer have been intensively
      studied in the past few years owing to their ability to be modified, their
      capacity to encapsulate a wide range of chemicals, their responsiveness to
      different factors, and the variety of functionalities with which they can be
      enhanced. Current research focuses on the development of carriers with remote
      guiding and activation (optical, magnetic or ultrasound), thereby addressing
      unique in vivo applications with multifunctional biomaterials. Submicron-sized
      capsules are good models to mimic biochemical processes in a confined geometry
      that imitates cell organelles. Moreover, the cellular and tissue-targeted
      delivery of the capsules might serve as an intracellular reporter or enzymatic
      reactor. However, several obstacles still have to be overcome before capsule
      technology can be implemented. This article discusses possible solutions as well
      as promising applications.

PMID- 17207547
TI  - The use of magnetic sensors to monitor moderate deep inspiration breath hold
      during breast irradiation with dynamic MLC compensators.
AB  - BACKGROUND AND PURPOSE: To reduce the dose to the heart during left breast
      irradiation, a moderate deep breath hold technique (MDIBH) was introduced.
      Originally, verification of the MDIBH was performed with portal images acquired
      in movie loop during the treatment delivery. However, this verification method is
      not compatible with the use of dynamic MLC compensation, recently introduced
      because of its often superior dose distribution. Magnetic sensors were evaluated
      as an additional/alternative method to monitor the breath hold. MATERIAL AND
      METHODS: In a first phase, the reproducibility of MDIBH for breast patients was
      evaluated by investigating for 19 patients the set-up errors derived from portal
      images in cine loop acquisition during MDIBH. In a second phase, for 10 patients,
      the breathing curves recorded by magnetic sensors were used to monitor beam-on
      and beam-off while portal images were simultaneously recorded in movie loop. In a
      third phase, breast patients treated with dynamic MLC compensation were trained
      for MDIBH and monitored with magnetic sensors. RESULTS: The interfraction
      reproducibility of MDIBH for the initial 19 patients was recorded: the mean set
      up error, the systematic and the random deviations are all smaller than 4mm in
      the anterior-posterior direction and in the cranio-caudal direction and smaller
      than 2 degrees along the rotation axis. Magnetic sensors provided a reproducible
      breathing curve: while the mean amplitude recorded for 10 patients varied
      substantially between patients, the individual standard deviation of the
      amplitude for each session was smaller than 3mm. For these 10 patients, the
      intrafraction set-up variation between the first portal image of two consecutive
      breath holds and the intra-breath hold set-up variation between the first and
      last portal image of each breath hold is smaller than 2mm in the anterior
      posterior direction, smaller than 3mm in the cranio-caudal direction and smaller
      than 1.5 degrees along the rotation axis. CONCLUSION: Using magnetic sensors to
      record the breathing curve of left breast patients in MDIBH, a verification
      method was developed, suitable for combining MDIBH with dynamic MLC compensation.

PMID- 17207548
TI  - Inhibition of cyclooxygenase-2 activity by celecoxib does not lead to
      radiosensitization of human prostate cancer cells in vitro.
AB  - PURPOSE: To evaluate the potential radiosensitizing effect of the specific COX-2
      inhibitor celecoxib (Celebrex) on prostate carcinoma cells in vitro. MATERIALS
      AND METHODS: The influence of celecoxib (concentration range 5 to 75 microM) on
      radiation-induced cellular and clonogenic survival was investigated in prostate
      carcinoma cell lines PC-3, DU145, LNCaP and normal prostate epithelial cells
      (PrEC). Western blot analysis and ELISA were used to determine the impact of
      radiation alone or radiation combined with celecoxib treatment on COX-2
      expression and prostaglandin E2 synthesis. To evaluate induction of celecoxib
      induced apoptosis cell cycle analysis has been performed. RESULTS: Celecoxib (5,
      10 and 25 microM) in combination with single-dose irradiation of 2 Gy induced a
      significant radiosensitization in normal prostate epithelial cells which could
      not be observed for any of the prostate carcinoma cell lines investigated.
      Increased COX-2 protein expression in PC-3 cells was obvious only after IR with
      15 Gy, while PGE2 production was elevated following irradiation (2-15 Gy) in a
      dose-dependent manner. Treatment with celecoxib alone or in combination with IR
      led to a dose-dependent increase in COX-2 protein expression. Nevertheless pre
      treatment with celecoxib caused a marked reduction of radiation-induced enzyme
      activity as tested at the level of PGE2 production, both in PC-3 and DU145 cells.
      Following fractionated irradiation with single doses of 2 Gy, elevated COX-2
      protein expression as well as enhanced PGE2 production was observed already after
      the second fraction in PC-3 cells. Pre-treatment with celecoxib reduced the
      amount of PGE(2) significantly, but not of COX-2 protein. CONCLUSIONS: Our data
      obtained for the human prostate cancer cell lines do not indicate that a marked
      inhibition of prostaglandin E2 synthesis by celecoxib leads to enhanced
      radiosensitization. Thus, in terms of radiosensitization the analysed prostate
      cancer cells can be classified as non-responders to celecoxib treatment.

PMID- 17207549
TI  - Use of a MS-electronic nose for prediction of early fungal spoilage of bakery
      products.
AB  - A MS-based electronic nose was used to detect fungal spoilage (measured as
      ergosterol concentration) in samples of bakery products. Bakery products were
      inoculated with different Eurotium, Aspergillus and Penicillium species,
      incubated in sealed vials and their headspace sampled after 2, 4 and 7 days. Once
      the headspace was sampled, ergosterol content was determined in each sample.
      Different electronic nose signals were recorded depending on incubation time.
      Both the e-nose signals and ergosterol levels were used to build models for
      prediction of ergosterol content using e-nose measurements. Accuracy on
      prediction of those models was between 87 and 96%, except for samples inoculated
      with Penicillium corylophilum where the best predictions only reached 46%.

PMID- 17207550
TI  - Prevalence, genetic diversity, and antibiotic resistance patterns of
      Campylobacter jejuni from retail raw chickens in Korea.
AB  - Campylobacter jejuni is a frequently detected food-borne pathogenic bacterium.
      Clinical cases are mostly sporadic but campylobacteriosis can have serious
      consequences, such as the development of Guillain-Barre syndrome as well as
      diarrheal diseases. We examined 265 retail raw chickens from Korean markets for
      the presence of C. jejuni using the US Food and Drug Administration standard
      cultural method and multiplex polymerase chain reaction (mPCR). The mPCR
      confirmed C. jejuni isolates were subtyped by pulsed field gel electrophoresis
      (PFGE) and flaA-typing for investigating the genetic diversity of the
      microorganism in retail raw chickens. Restriction enzymes SmaI and DdeI were used
      for PFGE and flaA-typing, respectively. Campylobacter spp. were found in 181
      samples (68.3%) and C. jejuni in 100 samples (37.74%). For C. jejuni, 73
      pulsotypes and 30 flaA types were detected. Antibiotic resistance tests performed
      by disk diffusion assay indicated that most C. jejuni isolates were resistant to
      tetracycline, nalidixic acid, and ciprofloxacin, and 87 composite types were
      revealed by PFGE, flaA-typing, and the antibiotic resistance tests. Our results
      show that the genetic diversity of C. jejuni isolates is very high and the
      correlation between genotype and antibiotic resistance was low even though many
      bacteria showed multi-drug resistance.

PMID- 17207551
TI  - Comparison of ventilatory threshold and exercise habits between Japanese men with
      and without metabolic syndrome.
AB  - OBJECTIVE: We compared the levels of ventilatory threshold (VT) and exercise
      habits in subjects with metabolic syndrome with those in age, sex-matched
      subjects without metabolic syndrome. METHODS: We used data of 155 Japanese men
      (47.1+/-9.2 years) with metabolic syndrome; the diagnosis was given by the
      definition and the diagnostic standard for metabolic syndrome in Japan. The
      influence of metabolic syndrome on oxygen uptake, work rate and heart rate at VT,
      and exercise habits were evaluated. RESULTS: Oxygen uptake and work rate at VT in
      subjects with metabolic syndrome were significantly lower than those in subjects
      without metabolic syndrome even after adjusting for body mass index (BMI). The
      number of subjects with exercise habits was significantly lower in metabolic
      syndrome. The subjects with exercise habits were significantly older than that in
      subjects without exercise habits. Furthermore, oxygen uptake and work rate at VT
      were significantly higher in subjects with exercise habits than those in subjects
      without exercise habits. CONCLUSION: Lower level of VT was characteristic in
      subjects with metabolic syndrome. Promotion of exercise habits is necessary for
      preventing and improving metabolic syndrome in Japanese men.

PMID- 17207552
TI  - Cadmium hyperaccumulation leads to an increase of glutathione rather than
      phytochelatins in the cadmium hyperaccumulator Sedum alfredii.
AB  - Sedum alfredii has been reported to be a cadmium (Cd) hyperaccumulator.
      Phytochelatins (PCs) and other thiol (SH)-containing compounds have been proposed
      to play an important role in the detoxification and tolerance of some heavy
      metals, but it is not clear whether PCs are responsible for Cd hyperaccumulation
      and tolerance in S. alfredii. In this study, two geographically isolated
      populations of S. alfredii were studied: one population grew on an old Pb/Zn mine
      site, while the other on a non-mine site. The mine population of this species
      exhibited a stronger heavy metal tolerance than in the other population. Root-to
      shoot transport of Cd was higher in population located at the mine site than at
      the non-mine site. Considerable amounts of Cd were accumulated in leaves and
      stems of mine plants, while most Cd was distributed in roots of non-mine plants.
      Non-protein SH in plant tissues of two populations were further investigated by a
      HPLC pre-column derivatization system. Upon exposure to Cd, no PCs were detected
      in all tissues of mine population, while an appreciable amount of glutathione
      (GSH) was observed in the descending order of stem>root>leaf. The concentrations
      of GSH consistently increased with the increase of exogenous Cd concentrations
      and time. On the contrary, Cd exposure strongly induced the production of PCs
      (mainly PC(2) and PC(3)) and GSH in plant tissues of non-mine population, and the
      concentrations of GSH showed an initial drop over the duration of 7-d exposure.
      The present results provided strong evidence that PCs are not involved in Cd
      transport, hyperaccumulation and tolerance in mine population of S. alfredii.

PMID- 17207553
TI  - Assessment of variability in acquired thermotolerance: potential option to study
      genotypic response and the relevance of stress genes.
AB  - High-temperature stress affects all growth stages of crops and ultimately yields.
      This is further aggravated by other environmental stresses like intermittent
      drought and high light. Management options are few and hence developing
      intrinsically tolerant plants is essential to combat the situation. As
      thermotolerance is a multigenic trait, emphasis needs to be on relevant
      approaches to assess genetic variability in basal and acquired tolerance. This is
      in fact the major aspect in crop improvement programmes. The relevance of
      temperature induction (acclimation) response (TIR), a high throughput approach to
      identify thermotolerant individuals and its utility as potential screening method
      is described here. This is based on the concept that stress-responsive genes are
      expressed only during initial stages of stress (acclimation stress) and bring
      about requisite changes in cell metabolism for adaptation. The fact that
      acclimation response is ubiquitous has been demonstrated in different crop plants
      in our studies and by others. Significance of acclimation in acquired tolerance
      and thus in assessing genetic variability in thermotolerance is discussed. The
      limitations of present approaches to validate the relevance of specific stress
      genes either in transgenics or in mutants or knock downs have been analyzed and
      the need to characterize transformants under conditions that trigger acquired
      tolerance is also highlighted. This review also focuses on the potential of
      exploiting acclimation response approach to improve the thermotolerance of crop
      plants by suitable breeding strategies.

PMID- 17207554
TI  - BcMF11, a putative pollen-specific non-coding RNA from Brassica campestris ssp.
      chinensis.
AB  - A full-length cDNA, BcMF11, has been cloned from Chinese cabbage (Brassica
      campestris L. ssp. chinensis Makino) using rapid amplification of the cDNA ends
      (RACE) based on a pollen-specific cDNA fragment (DN237921). The BcMF11 cDNA has a
      total length of 828bp with poly (A) tail. Analysis of the sequence demonstrated
      that BcMF11 is a novel non-coding RNA which has no prominent open reading frame
      (ORF) or coding capacity. No significant similarities were observed between
      BcMF11 and previously published sequences in GenBank. Transcription analysis
      indicated that BcMF11 is a novel pollen-specific ncRNA and may be involved in the
      pollen development of Chinese cabbage.

PMID- 17207555
TI  - Heterologous expression of the mutated melon ethylene receptor gene Cm-ERS1/H70A
      produces stable sterility in transgenic lettuce (Lactuca sativa).
AB  - The mutated melon ethylene receptor gene Cm-ERS1/H70A was introduced into tobacco
      and induced stable sterility in transgenic lines. This gene contains a missense
      mutation that converts the His(70) residue to Ala in the melon ethylene receptor
      gene Cm-ERS1. To test the applicability of this inducible sterility system to
      other plants, lettuce (Lactuca sativa) was transformed with the gene using
      Agrobacterium, and putative transformants containing Cm-ERS1/H70A were obtained.
      Thirteen randomly selected putative transformants were grown in a growth room
      under constant conditions, and seven of the lines showed sterility or
      significantly reduced fertility. DNA gel blot analysis confirmed the integration
      of the Cm-ERS1/H70A gene into the genomes of the putative transformants, and RT
      PCR and protein gel blot analysis confirmed the expression of Cm-ERS1/H70A mRNA
      and protein in all of the transformants. Five transformants showing sterility or
      reduced fertility when grown in a growth room under constant conditions were
      randomly selected to be grown in an open-air greenhouse under various
      environmental conditions. All five showed stable sterility under the various
      conditions. These results suggest that Cm-ERS1/H70A can induce sterility in
      heterologous transgenic plants.

PMID- 17207556
TI  - NPY and cohorts in human disease. Proceedings of the 8th International NPY
      Meeting. April 22-26, 2006. St. Petersburg, Florida, USA.

PMID- 17207557
TI  - Tracking of human Y receptors in living cells--a fluorescence approach.
AB  - Non-invasive methods for studying biological processes in living cells have
      become very important, also in the field of GPCR biochemistry. Great advancements
      in the application of fluorescence techniques as well as in the development and
      improvement of novel fluorophores allow the visualization of dynamic processes.
      Using these technologies, problems concerning receptor biosynthesis,
      internalization, recycling and degradation can be investigated. Here we compare
      the application of the different fluorescent tags EYFP, Lumiotrade mark and
      SNAPtrade mark to track hY(1) and hY(5) receptors in living cells.

PMID- 17207558
TI  - A role for pancreatic polypeptide in feeding and body weight regulation.
AB  - PP administration induces negative energy balance by suppressing food intake and
      gastric emptying while increasing energy expenditure in rodents. The mechanism of
      PP actions involves the changes in the expression of hypothalamic feeding
      regulatory peptides and the activity of the vago-vagal and vago-sympathetic
      reflex arc. PP-overexpressing mice we developed exhibited the thin phenotype with
      decreased food intake and gastric emptying rate. Plasma cholecystokinin (CCK)
      concentrations were increased in the transgenic mice and CCK-1 receptor
      antagonist improved the anorexia of the animals. These results, together with the
      previous notion of PP as an anti-CCK hormone in pancreatic exocrine secretion and
      gallbladder contraction, indicate that PP-CCK interactions may be either
      antagonistic or synergistic and the transgenic mice may exhibit the mixed
      phenotype by overproduction of PP and CCK.

PMID- 17207559
TI  - Development of a rat parathyroid hormone 2 receptor antagonist.
AB  - The parathyroid hormone 2 (PTH2) receptor is a Family B G-protein coupled
      receptor most highly expressed within the brain. Current evidence suggests that
      tuberoinfundibular peptide of 39 residues (TIP39) is the PTH2 receptor's
      endogenous ligand. To facilitate investigation of the physiological function of
      the PTH2 receptor/TIP39 system, we have developed a novel PTH2 receptor
      antagonist, by changing several residues within the amino terminal domain of
      TIP39. Histidine(4), tyrosine(5), tryptophan(6), histidine(7)-TIP39 binds the
      PTH2 receptor with high affinity, has over 30-fold selectivity for the rat PTH2
      receptor over the rat PTH1 receptor and displays no detectable agonist activity.
      This ligand should be useful for in vivo investigation of PTH2 receptor function.

PMID- 17207560
TI  - ANN-QSAR model for selection of anticancer leads from structurally heterogeneous
      series of compounds.
AB  - Developing a model for predicting anticancer activity of any classes of organic
      compounds based on molecular structure is very important goal for medicinal
      chemist. Different molecular descriptors can be used to solve this problem.
      Stochastic molecular descriptors so-called the MARCH-INSIDE approach, shown to be
      very successful in drug design. Nevertheless, the structural diversity of
      compounds is so vast that we may need non-linear models such as artificial neural
      networks (ANN) instead of linear ones. SmartMLP-ANN analysis used to model the
      anticancer activity of organic compounds has shown high average accuracy of
      93.79% (train performance) and predictability of 90.88% (validation performance)
      for the 8:3-MLP topology with different training and predicting series. This ANN
      model favourably compares with respect to a previous linear discriminant analysis
      (LDA) model [H. Gonzalez-Diaz et al., J. Mol. Model 9 (2003) 395] that showed
      only 80.49% of accuracy and 79.34% of predictability. The present SmartMLP
      approach employed shorter training times of only 10h while previous models give
      accuracies of 70-89% only after 25-46 h of training. In order to illustrate the
      practical use of the model in bioorganic medicinal chemistry, we report the in
      silico prediction, and in vitro evaluation of six new synthetic tegafur analogues
      having IC(50) values in a broad range between 37.1 and 138 microgmL(-1) for
      leukemia (L1210/0) and human T-lymphocyte (Molt4/C8, CEM/0) cells. Theoretical
      predictions coincide very well with experimental results.

PMID- 17207561
TI  - [Pronostic value of C-reactive protein measure in elderly patient with acquired
      pneumonia: correlation with Fine's score].
AB  - The Fine's score, a predictive score of infectious pneumonia gravity, does not
      integrate inflammatory parameters, which are routinely used in the management of
      infectious pneumonia. The aim of our study was to establish a correlation between
      the Fine's score and C reactive protein. PATIENTS AND METHODS: One hundred
      patients hospitalized for infectious pneumonia, 57 men and 43 female, with an
      average age of 85 years were retrospectively recorded. RESULTS: The median level
      of C reactive protein was 157 mg/L. Global mortality rate was 26% and
      respectively 5, 16 and 45% in the grades III, IV, V of the Fine's score. Beyond
      75,5 mg/L C reactive protein concentration, the mortality rate was contained
      between 28 and 32%. The comparison of the ROC curves of the Fine's score and C
      reactive protein did not showed any difference. CONCLUSION: C-Reactive protein is
      less precise than the Fine's score to assess infectious pneumonia gravity but
      seems to be an indicator of the potential gravity of the pneumonia.

PMID- 17207562
TI  - A comprehensive model for reproductive and developmental toxicity hazard
      identification: I. Development of a weight of evidence QSAR database.
AB  - A weight of evidence (WOE) reproductive and developmental toxicology (reprotox)
      database was constructed that is suitable for quantitative structure-activity
      relationship (QSAR) modeling and human hazard identification of untested
      chemicals. The database was derived from multiple publicly available reprotox
      databases and consists of more than 10,000 individual rat, mouse, or rabbit
      reprotox tests linked to 2134 different organic chemical structures. The reprotox
      data were classified into seven general classes (male reproductive toxicity,
      female reproductive toxicity, fetal dysmorphogenesis, functional toxicity,
      mortality, growth, and newborn behavioral toxicity), and 90 specific categories
      as defined in the source reprotox databases. Each specific category contained
      over 500 chemicals, but the percentage of active chemicals was low, generally
      only 0.1-10%. The mathematical WOE model placed greater significance on
      confirmatory observations from repeat experiments, chemicals with multiple
      findings within a category, and the categorical relatedness of the findings.
      Using the weighted activity scores, statistical analyses were performed for
      specific data sets to identify clusters of categories that were correlated,
      containing similar profiles of active and inactive chemicals. The analysis
      revealed clusters of specific categories that contained chemicals that were
      active in two or more mammalian species (trans-species). Such chemicals are
      considered to have the highest potential risk to humans. In contrast, some
      specific categories exhibited only single species-specific activities. Results
      also showed that the rat and mouse were more susceptible to dysmorphogenesis than
      rabbits (6.1- and 3.6-fold, respectively).

PMID- 17207563
TI  - Hemispheric differences in the time-course of semantic priming processes:
      evidence from event-related potentials (ERPs).
AB  - To investigate hemispheric differences in the timing of word priming, the
      modulation of event-related potentials by semantic word relationships was
      examined in each cerebral hemisphere. Primes and targets, either categorically
      (silk-wool) or associatively (needle-sewing) related, were presented to the left
      or right visual field in a go/no-go lexical decision task. The results revealed
      significant reaction-time and physiological differences in both visual fields
      only for associatively related word pairs, but an electrophysiological difference
      also tended to reach significance for categorically related words when presented
      in the left visual field. ERP waveforms showed a different time-course of
      associative priming effects according to the field of presentation. In the right
      visual field/left hemisphere, both N400 and Late Positive Component (LPC/P600)
      were modulated by semantic relatedness, while only a late effect was present in
      the left visual field/ right hemisphere.

PMID- 17207564
TI  - Cytotoxicity of chloroacetanilide herbicide alachlor in HepG2 cells independent
      of CYP3A4 and CYP3A7.
AB  - Alachlor is cytotoxic to human hepatoblastoma HepG2s, a cell line that expresses
      constitutive CYP3A7 and dexamethasone (DEX)-inducible CYP3A4 and CYP3A7. CYP3A4
      catalyzes alachlor N-dealkylation to 2-chloro-N-(2,6-diethylphenyl)acetamide
      (CDEPA), precursor of 2,6-diethylbenzoquinoneimine, putative reactive metabolite
      for rat nasal carcinogenicity. We hypothesized that HepG2 alachlor cytotoxicity
      would be mediated by CYP3A4/7 and increased with DEX. Here, we report time
      dependent alachlor cytotoxicity (EC(50) approximately 500 microM and 264+/-17
      microM at 6 and 24h, respectively) as assessed by lactate dehydrogenase leakage.
      DEX pretreatment (25 microM, 48 h) significantly increased CYP3A7-catalyzed
      luciferin 6' benzylether O-debenzylation, but had no effect on alachlor toxicity.
      Further, CYP3A4/7 inhibitor triacetyloleandomycin did not prevent, but rather
      potentiated, alachlor cytotoxicity. In agreement, CDEPA was less toxic than
      parent alachlor. HepG2 CYP3A4 activity was unaffected by 48 h DEX pretreatment;
      therefore, studies were done in DPX-2 cells, a HepG2 derivative engineered to
      overexpress pregnane-X receptor (PXR) that exhibits rifampicin (RIF)-inducible
      endogenous CYP3A4. Alachlor cytotoxicity in DPX-2 cells occurred over a
      concentration range equivalent to that in HepG2. CYP3A4 activity of DPX-2 cells
      treated with RIF (10 microM, 48 h) was twice that of untreated cells, but RIF did
      not increase alachlor toxicity. These results demonstrate that neither CYP3A4 nor
      CYP3A7 initiate a pathway leading to a toxic alachlor metabolite.

PMID- 17207565
TI  - Eruca sativa seeds possess antioxidant activity and exert a protective effect on
      mercuric chloride induced renal toxicity.
AB  - Mercuric chloride (HgCl(2)) is a well-known nephrotoxic agent. Increasing number
      of evidences suggest the role of oxidative stress in HgCl(2) induced
      nephrotoxicity. Eruca sativa is widely used in folklore medicines and has a good
      reputation as a remedy of renal ailments. In the present study, the antioxidant
      potential of ethanolic extract of E. sativa seeds was determined and its
      protective effect on HgCl(2) induced renal toxicity was investigated. The extract
      was found to possess a potent antioxidant effect, with a large amount of
      polyphenols and a high reducing ability. HPLC analysis of the extract revealed
      glucoerucin and flavonoids to be the major antioxidants present in it. E. sativa
      extract significantly scavenged several reactive oxygen species (ROS) and
      reactive nitrogen species (RNS). Feeding of the extract to rats afforded a
      significant protection against HgCl(2) induced renal toxicity. Subcutaneous
      administration of 4 mg/kg body weight HgCl(2) induced renal injury evident as a
      marked elevation in serum creatinine and blood urea nitrogen levels, and
      histopathological changes such as necrosis, oedema and congestion of stroma and
      glomeruli. Oxidative modulation of renal tissues following HgCl(2) exposure was
      evident from a significant elevation in lipid peroxidation and attenuation in
      glutathione (GSH) contents and activities of antioxidant enzymes viz., catalase
      (CAT), glutathione peroxidase (GPX), superoxide dismutase (SOD) and glutathione
      reductase (GR). Oral administration of E. sativa extract to rats at a dose
      regimen: 50-200 mg/kg body weight for 7 days prior to HgCl(2) treatment
      significantly and dose dependently protected against alterations in all these
      diagnostic parameters. The data obtained in the present study suggests E. sativa
      seeds to possess a potent antioxidant and renal protective activity and preclude
      oxidative damage inflicted to the kidney.

PMID- 17207566
TI  - A 40.7 kDa Rpp30/Rpp1 homologue is a protein subunit of Dictyostelium discoideum
      RNase P holoenzyme.
AB  - RNase P is an essential and ubiquitous endonuclease that mediates the maturation
      of the 5' ends of all precursor tRNA molecules. The holoenzyme from Dictyostelium
      discoideum possesses RNA and protein subunits essential for activity, but the
      exact composition of the ribonucleoprotein complex is still under investigation.
      Bioinformatic analysis of D. discoideum genome identified seven open reading
      frames encoding candidate RNase P protein subunits. The gene named drpp30 encodes
      a protein with a predicted molecular mass of 40.7 kDa that clusters with Rpp1 and
      Rpp30 RNase P protein subunits from Saccharomyces cerevisiae and human
      respectively, which have significantly lower molecular masses. Cloning and
      heterologous expression of DRpp30 followed by immunochemical analysis of RNase P
      active fractions demonstrates its association with RNase P holoenzyme.
      Furthermore, we show that DRpp30 can bind D. discoideum RNase P RNA and tRNA
      transcripts in vitro, giving a first insight of its possible role in D.
      discoideum RNase P function. Homology modeling using as a template the archaeal
      Ph1887p, and molecular dynamics simulations of the modeled structure suggest that
      DRpp30 adopts a TIM-barrel fold.

PMID- 17207567
TI  - Women's perception of sexuality around the menopause: outcomes of a European
      telephone survey.
AB  - OBJECTIVE: Women's attitudes and experience towards sexuality around the
      menopause were investigated in Europe by a telephone survey. In addition, it was
      qualified to what extent reduced sex drive and vaginal dryness affect personal
      life, taking into account cultural differences. STUDY DESIGN: A survey on 1,805
      post-menopausal women (age range: 50-60 years), experiencing at least one
      menopausal symptom (hot flushes or sleeplessness) or not menstruating for at
      least 1 year, was conducted in six European countries (United Kingdom, France,
      Germany, Italy, The Netherlands, Switzerland) by computer-assisted telephone
      interviewing. A structured interview analysed menopausal profile, sexuality
      related menopausal symptoms, mental well-being and attitudes towards sexuality.
      RESULTS: Apart from hot flushes or sleeplessness, women particularly experienced
      sexual symptoms, such as reduced sexual desire and vaginal pain/dryness during
      the menopausal transition: one third (34%) of the women mentioned experiencing a
      reduced sex drive whereas one half (53%) of the women noticed that they became
      less interested in sex in spite of the majority of the sample reporting finding
      it important to maintain an active sex life (71%). Sex is experienced as an
      important part of the relationship with a partner, especially for Italian and
      Swiss women and ageing seems to play a critical role in sexual functioning,
      particularly for Italian and Dutch women. A general positive attitude toward sex
      was supported by the evidence that almost half of the study sample reported
      having sexual contact at least four times a month. Mental and sexual well-being
      interfered with self-worth and enjoyment of life, as did vaginal discomfort.
      CONCLUSIONS: These data suggest that European middle-aged women experience the
      menopause as a process that brings about mood and sexual changes able to impair
      their personal life. However, cultural values and health beliefs influence
      perception of sexuality at the time of the menopause and will also influence the
      need for treatment.

PMID- 17207568
TI  - Differential flow cytometric detection of intracellular cytokines in peripheral
      and peritoneal mononuclear cells of women with endometriosis.
AB  - OBJECTIVE: The pathogenesis of endometriosis is related to functional changes in
      CD3+ and CD14+ cells observed both at the local and systemic level. Here we
      investigated whether, and if so, how the body compartment influences cytokine
      expression in stimulated peritoneal and peripheral CD3+ and CD14+ cells of women
      with endometriosis. STUDY DESIGN: Isolated peripheral blood (PB) and peritoneal
      fluid (PF) mononuclear cells from women with endometriosis were cultured under
      non-adherent conditions and stimulated with PMA and ionomycin for 6h to induce
      intracellular cytokine synthesis of TNF-alpha, IFN-gamma, and IL-8 by CD3+ cells
      or with LPS for 9h to produce TNF-alpha, IL-6, IL-10, MCP-1, and IL-8 by CD14+
      cells. RESULTS: The percentages of positive CD3+ cells stained for TNF-alpha and
      IFN-gamma were significantly higher and those stained for IL-8 were significantly
      lower in PF compared with PB, this being independent of the stage of
      endometriosis. In contrast, the percentages of CD14+ cells producing TNF-alpha,
      IL-6, IL-10, MCP-1, and IL-8 were significantly higher in PB than PF of women
      with endometriosis. CONCLUSIONS: Monocytes/macrophages and lymphocytes derived
      from the peripheral and peritoneal compartments of women with endometriosis
      differentially respond to stimulated cytokine synthesis induction. However, it is
      difficult to state whether the observed phenomenon is more related to body
      compartment influence per se or to the presence of endometriosis.

PMID- 17207569
TI  - Competing conservation goals, biodiversity or ecosystem services: element losses
      and species recruitment in a managed moorland-bracken model system.
AB  - Conservation management in Europe is often geared towards restoring semi-natural
      ecosystems, where the objective is to reverse succession and re-establish early
      successional communities, to comply with national and international conservation
      targets. At the same time, it is increasingly recognised that ecosystems provide
      services that contribute to other, possibly conflicting policy requirements. Few
      attempts have been made to define these conflicts. Here, we assess some potential
      conflicts using a Calluna vulgaris-dominated moorland invaded by bracken
      (Pteridium aquilinum) as a model system, where the current policy is to reverse
      this process and restore moorland. We examined impacts of bracken control
      treatments on services (stocks and losses of C and mineral nutrients), litter
      turnover and biodiversity within a designed experiment over 7 years. Bracken
      litter was >2000 g m(-2) in untreated plots, and treatments reduced this
      quantity, and its element content, to varying degrees. Cutting twice per year was
      the most successful treatment in reducing bracken litter and its element content,
      increasing litter turnover, and increasing both mass and diversity of non-bracken
      vegetation. Diversity was greatest where bracken litter had been reduced, but
      species composition was also influenced by light sheep grazing. There was a
      significant loss of some chemical elements from bracken that could not be
      accounted for in other pools, and hence potentially lost from the system. In
      absolute terms large amounts of C and N were lost, but when expressed as a
      percentage of the total amount in the system, Mg was potentially more important
      with losses of almost a third of the Mg in the surface soil-vegetation system.
      There is, therefore, a potential dilemma between controlling a mid-successional
      invasive species for conservation policy objectives, especially when that species
      has evolved to sequester nutrients, and the negative effect of increasing
      environmental costs in terms of carbon accounting required, the potential input
      of nutrients to aquatic systems, and long-term nutrient loss. There is,
      therefore, a need to balance conservation goals against potential damage to
      biogeochemical structure and function.

PMID- 17207570
TI  - A nonlinear model for assessing multiple probabilistic risks: a case study in
      South five-island of Changdao National Nature Reserve in China.
AB  - Several methods for estimating the potential impacts caused by multiple
      probabilistic risks have been suggested. These existing methods mostly rely on
      the weight sum algorithm to address the need for integrated risk assessment. This
      paper develops a nonlinear model to perform such an assessment. The joint
      probability algorithm has been applied to the model development. An application
      of the developed model in South five-island of Changdao National Nature Reserve,
      China, combining remote sensing data and a GIS technique, provides a reasonable
      risk assessment. Based on the case study, we discuss the feasibility of the
      model. We propose that the model has the potential for use in identifying the
      regional primary stressor, investigating the most vulnerable habitat, and
      assessing the integrated impact of multiple stressors.

PMID- 17207571
TI  - 1-O-alkylglycerols reduce the stimulating effects of bFGF on endothelial cell
      proliferation in vitro.
AB  - 1-O-alkylglycerols (alkyl-Gro) are natural etherlipids with multiple biological
      activities. We previously demonstrated that alkyl-Gro reduce endothelial
      permeability. Here we showed that alkyl-Gro reduced the basic Fibroblast Growth
      Factor (bFGF)-stimulated endothelial cell proliferation in a concentration
      dependent manner. The effects of 0.5 and 5 ng/ml bFGF on growth were completely
      suppressed after 72 h-treatment by 50 microM alkyl-Gro. Since bFGF greatly
      increased (+56%+/-15) the production of 1-O-alkyl-2-acyl-sn-glycerophosphate in
      alkyl-Gro-treated endothelial cells, our data suggest that the observed effects
      of alkyl-Gro could be mediated through PLD activation. Inhibition of bFGF
      stimulated endothelial proliferation could support anti-angiogenic activity of
      alkyl-Gro.

PMID- 17207572
TI  - Occlusal disharmony induces spatial memory impairment and hippocampal neuron
      degeneration via stress in SAMP8 mice.
AB  - We examined the effect of occlusal disharmony in senescence-accelerated (SAMP8)
      mice on plasma corticosterone levels, hippocampal neuron number, and spatial
      performance in the water maze. The bite-raised condition was associated with an
      accelerated age-related decline in spatial memory, increased plasma
      corticosterone levels, and a decreased number of neurons in the hippocampal CA3
      region. The findings suggest that the bite-raised condition in aged SAMP8 mice
      induces hippocampal neuron loss, thereby leading to senile memory deficits.

PMID- 17207573
TI  - Fluoxetine attenuates the effects of pentylenetetrazol on rat freezing behavior
      and c-Fos expression in the dorsomedial periaqueductal gray.
AB  - The aim of the study was to investigate the role of the periaqueductal gray (PAG)
      in anxiolytic-like actions of fluoxetine in animals treated with an anxiogenic
      drug, pentylenetetrazol (PTZ), and subjected to fear conditioning procedure. The
      data showed that PTZ given at the dose of 30 mg/kg 15 min before a retention
      trial significantly decreased freezing reaction (p<0.01), and potently enhanced
      rat locomotor activity (p<0.01), in comparison to the control group. These
      effects were reversed by prior (60 min) administration of fluoxetine (20 mg/kg).
      Simultaneously, PTZ significantly increased c-Fos expression in the dorsomedial
      periaqueductal gray (DMPAG), examined 2h after the retention trial, in comparison
      to the control group (p<0.01). Fluoxetine (20 mg/kg) administered 60 min before
      PTZ reversed this effect. PTZ given at the same dose and time interval in the
      open field test did not affect rat locomotor behavior. Importantly, fluoxetine
      pretreatment did not change PTZ concentration in brain tissue. Our experiment
      based on PTZ-enhanced aversive conditioning revealed that acutely administered
      fluoxetine antagonized PTZ-induced panic-like behavior, and this phenomenon was
      accompanied by inhibition of activity of DMPAG.

PMID- 17207574
TI  - Delta opioid receptors stimulation with [D-Ala2, D-Leu5] enkephalin does not
      provide neuroprotection in the hippocampus in rats subjected to forebrain
      ischemia.
AB  - It has been reported that delta opioid agonists can have neuroprotective efficacy
      in the central nervous system. This study was conducted to test the hypothesis
      that a delta opioid receptor (DOR) agonist, [D-Ala2, D-Leu5] enkephalin (DADLE),
      can improve neuron survival against experimental forebrain ischemia in rats.
      Using male rats (n=125), intraperitoneal injection of DADLE (0, 0.25, 1, 4, 16 mg
      kg-1) was performed 30 min before ischemia. Ten minutes interval forebrain
      ischemia was provided by the bilateral carotid occlusion combined with
      hypotension (35 mm Hg) under isoflurane (1.5%) anesthesia. All animals were
      neurologically and histologically evaluated after a recovery period of 1 week. As
      histological evaluation, percentages of ischemic neurons in the CA1, CA3, dentate
      gyrus (DG) were measured. During the recovery period, 27 rats died because of
      apparent upper airway obstruction, seizure, or unidentified causes. There were no
      differences in the motor activity score among the groups. Ten minutes forebrain
      ischemia induced approximately 75, 20, and 10% neuronal death in the CA1, CA3,
      and DG, respectively. Any doses of DADLE did not attenuate neuronal injury in the
      hippocampus after ischemia. Pre-ischemic treatment of DORs agonism with DADLE did
      not provide any neuroprotection to the hippocampus in rats subjected to forebrain
      ischemia.

PMID- 17207575
TI  - Developmental differences in neuromodulation and synaptic properties in the
      lamprey spinal cord.
AB  - Functional properties in the spinal cord change during development to adapt motor
      outputs to differing behavioral requirements. Here, we have examined whether
      there are also developmental differences in spinal cord plasticity by comparing
      the neuromodulatory effects of substance P in the larval lamprey spinal cord with
      its previously characterized effects in premigratory adults. The premigratory
      adult effects of substance P were all significantly reduced in larvae. As the
      adult effects of substance P depend on the N-methyl-d-aspartate (NMDA)-dependent
      potentiation of glutamatergic synaptic transmission, we examined if the
      developmental differences in neuromodulation were associated with differences in
      synaptic properties. We found that the amplitude, rise time, and half-width of
      excitatory postsynaptic potentials (EPSPs) from excitatory network interneurons
      were all significantly reduced in larvae compared with adults. These differences
      were associated with a reduction in the NMDA component of larval EPSPs, an effect
      that could have contributed to the reduced modulatory effects of substance P in
      larvae. In contrast to glutamatergic inputs, the amplitude, rise time, and half
      width of inhibitory postsynaptic potentials (IPSPs) from ipsilateral inhibitory
      interneurons were all significantly increased in larvae compared with adults.
      Substance P also potentiated larval IPSP amplitudes, an effect not seen in
      adults. This increase in inhibition contributed to the reduced effects of
      substance P in larvae, as premigratory adult-like modulation could be evoked when
      inhibition was blocked with strychnine. These results suggest that opposite
      developmental changes in excitatory and inhibitory synaptic transmission and
      their modulation are associated with developmental differences in spinal cord
      neuromodulation.

PMID- 17207576
TI  - A rotenone-sensitive site and H2O2 are key components of hypoxia-sensing in
      neonatal rat adrenomedullary chromaffin cells.
AB  - In the perinatal period, adrenomedullary chromaffin cells (AMC) directly sense
      PO2 and secrete catecholamines during hypoxic stress, and this response is lost
      in juvenile ( approximately 2 week-old) chromaffin cells following postnatal
      innervation. Here we tested the hypothesis that a rotenone-sensitive O2-sensor
      and ROS are involved in the hypoxic response of AMC cultured from neonatal and
      juvenile rats. In whole-cell recordings, hypoxia (PO2=5-15 mm Hg) inhibited
      outward current in neonatal AMC; this response was reversed by exogenous H2O2 and
      mimicked and occluded by intracellular catalase (1000 units/ml), as well as the
      antioxidants, N-acetyl-L-cysteine (NAC; 50 microM) and Trolox (200 microM). Acute
      hypoxia decreased ROS levels and stimulated ATP secretion in these cells, as
      measured by luminol and luciferin-luciferase chemiluminescence, respectively. Of
      several mitochondrial electron transport chain (ETC) inhibitors tested, only
      rotenone, a complex I blocker, mimicked and occluded the effects of hypoxia on
      outward current, cellular ROS, and ATP secretion. Succinate donors, which act as
      complex II substrates, reversed the effects of hypoxia and rotenone in neonatal
      AMC. In contrast, in hypoxia-insensitive juvenile AMC, neither NAC nor rotenone
      stimulated ATP secretion though they both caused a decrease in ROS levels. We
      propose that O2-sensing by neonatal AMC is mediated by decreased ROS generation
      via a rotenone-sensitive site that is coupled to outward current inhibition and
      secretion. Interestingly, juvenile AMC display at least two modifications, i.e.
      an uncoupling of the O2-sensor from ROS regulation, and an apparent insensitivity
      of outward current to decreased ROS.

PMID- 17207577
TI  - Calcium/calmodulin kinase kinase beta has a male-specific role in memory
      formation.
AB  - The calcium/calmodulin (CaM) kinase cascade regulates gene transcription, which
      is required for long-term memory formation. Previous studies with Camkk2 null
      mutant mice have shown that in males calcium/calmodulin kinase kinase beta
      (CaMKKbeta) is required for spatial memory formation and for activation of the
      transcription factor cyclic AMP-responsive element binding protein (CREB) in the
      hippocampus by spatial training. Here we show that CaMKKbeta is not required for
      spatial memory formation in female mice as female Camkk2 null mutants were not
      impaired in spatial memory formation and they had the same level of hippocampal
      CREB phosphorylation after spatial training as female wild-type mice.
      Furthermore, we show that male but not female Camkk2 null mutants were impaired
      in long-term potentiation (LTP) at hippocampal CA1 synapses. Finally, a
      transcriptional analysis of male Camkk2 null mutants led to the identification of
      a gene, glycosyl phosphatidyl-inositol anchor attachment protein 1 (GAA1), whose
      hippocampal mRNA expression was up-regulated by spatial and contextual training
      in male but not in female wild-type mice. Taken together, we conclude that
      CaMKKbeta has a male-specific function in hippocampal memory formation and we
      have identified male-restricted transcription occurring during hippocampal memory
      formation.

PMID- 17207578
TI  - Differential expression patterns of chloride transporters, Na+-K+-2Cl-
      cotransporter and K+-Cl--cotransporter, in epilepsy-associated malformations of
      cortical development.
AB  - Malformations of cortical development are recognized causes of chronic medically
      intractable epilepsy. An increasing number of observations suggests an important
      role for cation-chloride co-transporters (CCTs) in controlling neuronal function.
      Deregulation of their expression may contribute to the mechanisms of
      hyperexcitability that lead to seizures. In the present study the expression and
      cell-specific distribution of Na+-K+-2Cl--cotransporter (NKCC1) and K+-Cl-
      cotransporter (KCC2) were studied immunocytochemically in different developmental
      lesions, including focal cortical dysplasia (FCD) type IIB (n=9),
      hemimegalencephaly (HMEG, n=6) and ganglioglioma (GG, n=9) from patients with
      medically intractable epilepsy and in age-matched controls. In normal control
      adult cortex, NKCC1 displayed low neuronal and glial expression levels. In
      contrast KCC2 showed strong and diffuse neuropil staining. Notable glial
      immunoreactivity (IR) was not found for KCC2. NKCC1 was highly expressed in the
      majority of FCD, HMEG and GG specimens. NKCC1 IR was observed in neurons of
      different size, including large dysplastic neurons, in balloon cells (in FCD and
      HMEG cases) and in glial cells with astrocytic morphology. The immunoreactivity
      pattern of KCC2 in FCD, HMEG and GG specimens was characterized by less neuropil
      staining and more intrasomatic IR compared with control. KCC2 IR was observed in
      neurons of different size, including large dysplastic neurons, but not in balloon
      cells or in glial cells with astrocytic morphology. Double-labeling experiments
      confirmed the differential cellular distribution of the two CCTs and their
      expression in GABA(A) receptor (alpha1 subunit)-positive dysplastic neurons. The
      cellular distribution of CCTs, with high expression of NKCC1 in dysplastic
      neurons and altered subcellular distribution of KCC2 resembles that of immature
      cortex and suggests a possible contribution of CCTs to the high epileptogenicity
      of malformations of cortical development.

PMID- 17207579
TI  - Different mechanisms account for extracellular-signal regulated kinase activation
      in distinct brain regions following global ischemia and reperfusion.
AB  - Oxidative stress after cerebral ischemia and reperfusion activates extracellular
      signal-regulated kinases (ERK) in brain. However, the mechanism of this
      activation has not been elucidated. We have previously reported that in an in
      vitro model of oxidative stress in immature cortical neuronal cultures, the
      inhibition of ERK phosphatase activity contributes to ERK1/2 activation and
      subsequent neuronal toxicity. This study examined whether ERK activation was
      associated with altered activity of ERK phosphatases in a rat cardiac arrest
      model. Rats in experimental groups were subjected to asphyxial cardiac arrest for
      8 min and then resuscitated for 30 min. Significant ERK activation was detected
      in both cortex and hippocampus following ischemia/reperfusion by immunoblotting.
      ERK phosphatase activity was reversibly inhibited in cerebral cortex but not
      affected in hippocampus following ischemia/reperfusion. MEK1/2 was activated in
      both cerebral cortex and hippocampus following ischemia/reperfusion. Using a
      specific inhibitor of protein phosphatase 2A (PP2A), okadaic acid (OA), we have
      identified PP2A to be the major ERK phosphatase that is responsible for
      regulating ERK activation in ischemic brain tissues. Orthovanadate inhibited ERK
      phosphatase activity in brain tissues, suggesting that tyrosine phosphatases and
      dual specificity phosphatases may also contribute to the ERK phosphatase activity
      in brain tissues. Together, these data implicate ERK phosphatase in the
      regulation of ERK activation in distinct brain regions following global ischemia.

PMID- 17207580
TI  - Calcineurin (protein phosphatase 2B) is involved in the mechanisms of action of
      antidepressants.
AB  - Calcineurin (PP2B) is a Ca(2+)-dependent protein phosphatase enriched in the
      brain that takes part in intracellular signaling pathways regulating synaptic
      plasticity and neuronal functions. Calcineurin-dependent pathways are important
      for complex brain functions such as learning and memory. More recently, they have
      been suggested to play a role in the processing of emotional information. The aim
      of this study was to investigate whether calcineurin may be involved in the
      effect of antidepressants. We first found that chronic antidepressant treatment
      in mice leads to an increase of calcineurin levels in the hippocampus. We then
      studied the behavioral and molecular responses to fluoxetine of mice with a
      genetic overactivation of calcineurin in the hippocampus (constitutively
      activated calcineurin transgenic mouse line #98, CN98 mice). We observed that
      CN98 mice are more sensitive to the behavioral effect of fluoxetine and
      desipramine tested in the tail suspension test. Moreover, the basal expression of
      growth factor brain-derived neurotrophic factor and subunit 1 of AMPA glutamate
      receptor, GluR1, both of which are modified after chronic antidepressant
      administration, are altered in the hippocampus of CN98 mice. These results
      suggest that calcineurin-dependent dephosphorylation plays an important role in
      the mechanisms of action of antidepressants, providing a new starting point for
      developing improved therapeutic treatments for depression.

PMID- 17207581
TI  - Localization and glucocorticoid regulation of 11beta-hydroxysteroid dehydrogenase
      type 1 mRNA in the male mouse forebrain.
AB  - The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts the
      inactive 11-dehydrocorticosterone into the active glucocorticoid corticosterone.
      There is accumulating evidence indicating widespread expression of 11beta-HSD1 in
      the brain. However, there is little information about regulation of 11beta-HSD1
      expression in this tissue. Using in situ hybridization involving use of 35S
      labeled cRNA probe, we have studied the distribution of cells expressing 11beta
      HSD1 mRNA in the male mouse forebrain as well as the effects of adrenalectomy
      (ADX) and acute administration of corticosterone (3 and 24 h) on 11beta-HSD1 mRNA
      levels. Cells expressing 11beta-HSD1 mRNA were mostly detected in the cerebral
      cortex, hippocampus, amygdala and medial preoptic area, with the highest
      expression in the cerebral cortex (retrosplenial granular area) and hippocampus
      (CA3 and granular layer of the gyrus dentatus). Seven days following ADX, 11beta
      HSD mRNA levels were increased by 50% in the gyrus dentatus, by 100% in the CA3
      area, and 105% in the cerebral cortex. Administration of corticosterone to ADX
      mice induced a significant decrease in mRNA, in both the hippocampus and cerebral
      cortex so that, at the 24 h time interval, the levels were similar to those
      observed in intact mice. These results clearly indicate that circulating
      corticosterone is downregulating the expression of 11beta-HSD1 mRNA in the two
      forebrain areas studied. This downregulation might contribute to maintain low
      intracellular corticosterone levels in central regions and then prevent the
      deleterious effects induced by high glucocorticoid levels.

PMID- 17207582
TI  - Glutamate stimulates glutamate receptor interacting protein 1 degradation by
      ubiquitin-proteasome system to regulate surface expression of GluR2.
AB  - The glutamate receptor interacting protein 1 (GRIP1) is a scaffolding protein in
      postsynaptic density (PSD), tethering AMPA receptors to other signaling proteins.
      Here we report that glutamate stimulation caused a rapid reduction in protein
      levels of GRIP1, but not that of glutamate receptor (GluR) 1, GluR2 and protein
      interacting with C kinase 1 (PICK1) in rat primary cortical neuron cultures. Down
      regulation of GRIP1 by glutamate was blocked by carbobenzoxyl-leucinyl-leucinyl
      leucinal (MG132), a proteasome inhibitor and by expression of K48R-ubiquitin, a
      dominant negative form of ubiquitin. The GRIP1 reduction was inhibited by MK-801,
      an N-methyl-d-aspartate (NMDA) receptor antagonist, but not by 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX), an AMPA receptor antagonist. EGTA and 1,2
      bis(2-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid tetrakis (BAPTA), two Ca2+
      chelators, but not nifedipine, an L-type Ca2+ channel blocker, prevented GRIP1
      degradation. Furthermore, MG132 prevented glutamate-stimulated reduction in
      surface amount of GluR2, and knockdown of GRIP1 by RNAi against GRIP1 reduced
      surface GluR2 in neurons. Our results suggest that glutamate induces GRIP1
      degradation by proteasome through an NMDA receptor-Ca2+ pathway and that GRIP1
      degradation may play an important role in regulating GluR2 surface expression.

PMID- 17207583
TI  - Anesthesia suppresses nonsynchronous responses to repetitive broadband stimuli.
AB  - Although many aspects of sensory processing are qualitatively similar in awake
      and anesthetized subjects, important state-dependent differences are known to
      exist. To investigate the effects of anesthesia on temporal processing in rat
      auditory cortex, multi-unit neural responses to trains of broadband clicks were
      recorded prior to, 15 min following, and 5 h following the administration of a
      ketamine-based anesthetic. While responses to clicks in isolation were relatively
      stable between states, responses to subsequent clicks exhibited increases in
      latency, peak latency, response duration, and post-onset suppression under
      anesthesia. Ketamine anesthetic reduced the maximum rate at which multi-unit
      clusters entrained to repeated clicks. No multi-unit clusters entrained to
      stimulus presentation rates greater than 33 Hz under anesthesia, compared with
      85% and 81% in the pre- and post-anesthetic condition, respectively. Anesthesia
      also induced oscillatory activity that was not present in awake subjects.
      Finally, ketamine anesthesia abolished all tonic excitatory and suppressive
      nonsynchronous responses to click trains. The results of this study suggest that
      ketamine-based anesthesia significantly alters neural coding of broadband click
      trains in auditory cortex.

PMID- 17207584
TI  - Nicotinic acetylcholine receptor antagonistic property of the selective dopamine
      uptake inhibitor, GBR-12909 in rat hippocampal slices.
AB  - Previously we found that inhibitors of noradrenaline (NA) and/or 5-HT reuptake
      are able to inhibit neuronal nicotinic acetylcholine receptors (nAChRs) in the
      CNS most probably by a channel blocker-type mechanism. The aim of our study was
      to clarify whether selective dopamine uptake inhibitors also possess this
      property, therefore we investigated the effect of GBR-12909 on the nicotine
      evoked release of [3H]NA from rat hippocampal slices. GBR-12909, similar to
      selective NA and 5-HT uptake blockers, inhibited the nicotine-evoked release with
      an IC50 of 2.32 microM. The ability of monoamine uptake blockers to inhibit
      nicotine-evoked [3H]NA release (IC50) and NA reuptake (Ki) showed no correlation,
      indicating that the NA uptake system is not involved in the inhibition of the
      response to nicotine. Previously we have shown in whole cell patch clamp
      experiments, that GBR-12909, depending on the stimulation pattern, inhibits Na+
      currents with an IC50 in the 6-35 microM concentration range [Mike A, Karoly R,
      Vizi ES, Kiss JP (2003) Inhibitory effect of the DA uptake blocker GBR-12909 on
      sodium channels of hippocampal neurons. Neuroreport 14:1945-1949]. To study
      whether the inhibition of Na+-channels is involved in the action of GBR-12909 on
      the nicotine-evoked [(3)H]NA release, we compared the effect of GBR-12909 and the
      Na(+)-channel blocker tetrodotoxin (TTX) on the electrical stimulation- and
      nicotine-evoked response. TTX prevented the release of [3H]NA induced by both
      types of stimulation, whereas GBR-12909 inhibited only the nicotine-induced
      response, indicating that under our experimental conditions the target of GBR
      12909 is not the Na+-channel. These data indicate that the selective DA uptake
      inhibitor GBR-12909 is able to inhibit nAChRs, that is, the nAChR antagonistic
      property of monoamine uptake inhibitors is independent of their selectivity. The
      fact that monoamine uptake inhibitors with different chemical structure and
      selectivity are able to inhibit nAChRs may reveal some common properties of
      nicotinic receptors and monoamine uptake carriers.

PMID- 17207585
TI  - Immune, health and endocrine characteristics of depressed postpartum mothers.
AB  - The purpose of the study was to examine demographic, immune, endocrine, stress
      and health characteristics of depressed mothers, measured between 4 and 6 weeks
      postpartum, and compare them to non-depressed mothers. The top decile (N=25) of
      Profile of Mood States depression scores was used to categorize mothers as
      depressed and these data were then compared to means of the remaining mothers
      (N=175) in a study of stress and immunity during the postpartum. Depressed
      mothers were younger, had smaller birth weight infants, and their babies
      experienced more illness symptoms at 4-6 weeks postpartum. Depressed mothers were
      less likely to be breastfeeding and had lower serum prolactin levels. Depressed
      mothers were more likely to smoke, to have daytime sleepiness, and more symptoms
      of infection than non-depressed mothers. Depressed mothers also had higher
      perceived stress, postpartum stress, and negative life event reports. There was
      evidence suggesting that depressed mothers had a downregulated hypothalamic
      pituitary-adrenocortical (HPA) axis, in that salivary cortisol was lower in
      depressed mothers. Depressed mothers also had lower serum levels of Interferon
      gamma (IFN-gamma) and a lower IFN-gamma/Interleukin-10 (IL-10) ratio in both sera
      and in whole blood stimulated cultures, suggesting a depressed Th1/Th2 ratio in
      depressed mothers. The data supports the possibility that postpartum depression
      may be associated with a dysregulated HPA axis and possible depressed cellular
      immunity.

PMID- 17207586
TI  - Expression of nuclear and cytoplasmic phosphorylated FADD in gastric cancers.
AB  - Fas-associated death domain (FADD) plays a crucial role during death receptor
      mediated apoptosis. In addition, FADD possesses apoptosis-independent activities,
      including cell-cycle regulation and cell proliferation regulated by the
      phosphorylation of FADD at Ser194. The aim of this study was to explore the
      possibility whether alteration of phosphorylated FADD (p-FADD) expression might
      be a characteristic of gastric cancer. We analyzed the expression of p-FADD
      protein in 60 gastric adenocarcinomas by immunohistochemistry using a tissue
      microarray approach. In the normal gastric mucosal cells, surface and glandular
      epithelial cells evenly expressed p-FADD in the nuclei but not in the cytoplasm.
      In the cancers, p-FADD expression was detected in 38 cases (63%) of the gastric
      carcinomas, but there was no p-FADD immunostaining in the remaining 22 cancers
      (37%). Of note, p-FADD immunostaining was observed in cytoplasm/nuclei (20
      cancers; 33%) and cytoplasm (18 cancers; 30%). There was no significant
      association of p-FADD expression with clinocopathological characteristics,
      including invasion, metastasis, and stage. Our data showed that the expression of
      p-FADD in gastric cancers was heterogenous in its location compared to the
      uniform nuclear expression of p-FADD in normal gastric cells. Many of the cancers
      (67%) were devoid of nuclear p-FADD, suggesting that p-FADD functions in the
      nucleus may be perturbed in the cancers. Also, p-FADD expression in the cytoplasm
      in a large fraction of the cancers (63%), not seen in the normal cells, suggested
      that the cell death functions of p-FADD could be altered in the cancer cells.

PMID- 17207587
TI  - A novel group of type I polyketide synthases (PKS) in animals and the complex
      phylogenomics of PKSs.
AB  - Type I polyketide synthases (PKSs), and related fatty acid synthases (FASs),
      represent a large group of proteins encoded by a diverse gene family that occurs
      in eubacteria and eukaryotes (mainly in fungi). Collectively, enzymes encoded by
      this gene family produce a wide array of polyketide compounds that encompass a
      broad spectrum of biological activity including antibiotic, antitumor,
      antifungal, immunosuppressive, and predator defense functional roles. We employed
      a phylogenomics approach to estimate relationships among members of this gene
      family from eubacterial and eukaryotic genomes. Our results suggest that some
      animal genomes (sea urchins, birds, and fish) possess a previously unidentified
      group of pks genes, in addition to possessing fas genes used in fatty acid
      metabolism. These pks genes in the chicken, fish, and sea urchin genomes do not
      appear to be closely related to any other animal or fungal genes, and instead are
      closely related to pks genes from the slime mold Dictyostelium and eubacteria.
      Continued accumulation of genome sequence data from diverse animal lineages is
      required to clarify whether the presence of these (non-fas) pks genes in animal
      genomes owes their origins to horizontal gene transfer (from eubacterial or
      Dictostelium genomes) or to more conventional patterns of vertical inheritance
      coupled with massive gene loss in several animal lineages. Additionally, results
      of our broad-scale phylogenetic analyses bolster the support for previous
      hypotheses of horizontal gene transfer of pks genes from bacterial to fungal and
      protozoan lineages.

PMID- 17207588
TI  - Identification and characterization of rad51 of Pneumocystis.
AB  - Rad51, a eukaryotic homolog of RecA, is an important protein involved in DNA
      recombination and repair. We have characterized rad51 of Pneumocystis carinii and
      Pneumocystis murina. rad51 is a single copy gene that encodes a 1.2 kb mRNA,
      which contains an open reading frame encoding 343 amino acids. Rad51 from
      Pneumocystis showed high homology to those from yeast. ATP binding motifs
      GEFRTGKS and LLIVD, similar to those of Saccharomyces cerevisiae and
      Schizosaccharomyces pombe, are conserved in Pneumocystis Rad51. The recombinant
      protein when expressed in E. coli showed DNA-dependent ATPase activity. Since
      Rad51 is a key enzyme in DNA repair and recombination, it potentially plays an
      important role in the recombination process leading to antigenic variation and
      thereby resistance to host immune responses in Pneumocystis.

PMID- 17207589
TI  - The role of glutathione in the regulation of nucleotide excision repair during
      oxidative stress.
AB  - Nucleotide excision repair (NER) mainly repairs bulky DNA adducts and helix
      distorting lesions, but is additionally considered to be a back-up system for
      base excision repair to remove oxidative stress induced DNA damage. Therefore, it
      can be speculated that NER is up-regulated or primed by oxidative stress.
      Exposure of human pulmonary epithelial cells (A549) to non-toxic doses of 100muM
      H(2)O(2) indeed showed a 2 to 4.5-fold increase in expression of XPA, XPC, ERCC4,
      and ERCC5, whereas the expression of ERCC1 was 5-fold decreased. Phenotypical
      assessment of NER capacity (i.e. recognition and incision of benzo[a]pyrene-DNA
      adducts) showed a significant decrease to less than 50% after H(2)O(2) exposure,
      which paralleled the effects of H(2)O(2) on ERCC1 expression. To study the
      possible involvement of glutathione (GSH) in the regulation of NER, cells were
      pre-incubated with 0.5mM BSO, resulting in total GSH depletion and increased
      intracellular oxidative stress. In GSH-depleted cells, the down-regulation of
      ERCC1 expression by H(2)O(2) was completely abolished and the up-regulation of
      ERCC4 expression was potentiated from 2.5-fold to >10-fold. Similarly, the
      H(2)O(2)-induced decrease in NER capacity was absent in GSH-depleted cells.
      Overall, our data suggest that NER capacity as well as the expression of NER
      related genes can be modulated by oxidative stress. ERCC1 expression and NER
      capacity correlated strongly (R(2)=0.85, P<0.01) after oxidant exposure,
      indicating ERCC1 as a specific target for oxidative stress induced modification
      of NER.

PMID- 17207590
TI  - Seasonal changes in ovarian activity: lessons learnt from the horse.
AB  - The annual reproductive cycle in the horse involves a reduction in ovarian
      activity during short days. The absence of ovulatory activity during winter has
      important consequences for an equine industry eager to breed mares early during
      the year. The anovulatory season results from a reduction in the secretion of
      pituitary gonadotropin that is in turn triggered by the inhibitory effects of
      short photoperiod on the hypothalamus-pituitary axis. Recent studies have
      provided evidence that the response of the ovaries to endocrine stimuli during
      the anovulatory season is affected not only by circulating concentrations of
      trophic hormones but also by locally produced growth factors that are putative
      modulators of follicular responses to gonadotropins. The present review
      summarises current knowledge on ovarian dynamics during the equine anovulatory
      season and the regulatory mechanisms involved at both systemic and local levels.

PMID- 17207591
TI  - Formulation, lyophilization and solid-state properties of a pegylated protein.
AB  - In this paper the importance of formulation and process parameters on the solid
      state properties of a lyophilized, pegylated growth hormone antagonist
      (pegvisomant) was studied. The degree of solid-state disorder (amorphicity),
      protein/polyethylene glycol (PEG)/sucrose interactions, and dissolution
      characteristics of the resultant cakes were examined. Using isothermal
      microcalorimetry (IMC) and differential scanning calorimetry (DSC), it was shown
      that in co-lyophilized pegylated protein/sucrose systems there was an interaction
      between sucrose and pegylated protein molecules. This interaction was evidenced
      by a decrease in the melting temperature (Tm) and melting enthalpy of PEG as a
      function of sucrose concentration. It was also shown that the sum of the heat of
      interaction with water for the individual constituents, lyophilized pegylated
      protein and lyophilized sucrose, was higher than the heat of interaction for the
      co-lyophilized system. As the concentration of sucrose was increased, the degree
      of solid-state disorder increased and the solid dissolved faster. A correlation
      was found among heat of interaction with water, degree of solid-state disorder,
      and dissolution time. Pegylation caused a shorter dissolution time, lower
      moisture content, increased amorphicity, and a more rapid moisture-induced
      crystallization of sucrose.

PMID- 17207592
TI  - Controlled drug delivery to the lung: Influence of hyaluronic acid solution
      conformation on its adsorption to hydrophobic drug particles.
AB  - This work reports investigations into the interaction and adsorption of the
      hydrophilic polymer hyaluronic acid (HA) onto the surface of the hydrophobic
      corticosteroid drug fluticasone propionate (FP). The eventual aim is to formulate
      a bioadhesive pulmonary drug delivery system with prolonged action that avoids
      rapid clearance from the lungs by the mucociliary escalator. Adsorption isotherms
      detailing the adsorption of HA from aqueous HA solution concentrations ranging
      from 0.14 to 0.0008% (w/v) to a fixed FP particle concentration of 0.1% (w/v)
      were investigated. The method of preparing FP particles with HA molecules
      adsorbed on their surfaces (FP/HA particles) involved suspension of the FP either
      in hydrated HA solution or in water followed by addition of solid HA,
      centrifugation of the solids to form a pellet, washing the pellet several times
      with water until no HA was found in the supernatant and then freeze drying the
      suspension obtained by dispersing the final pellet. The freeze dried powder was
      then analysed for adsorbed HA using a Stains-all assay. The influence of order of
      addition of HA to FP, time for the adsorption process, and temperature of
      preparation on the adsorption isotherms was investigated. The non-equilibrium
      adsorption isotherms produced generally followed the same trend, in that as the
      HA solution concentration increased, the amount of HA adsorbed increased to a
      maximum at a solution concentration of approximately 0.1% (w/v) and then
      decreased. The maxima in the adsorption isotherms were close to the change from
      secondary to tertiary conformation in the HA solutions. Below the maxima,
      adsorption occurred via interaction of FP with the hydrophobic patches along the
      HA chains in the secondary structures. Above the maxima, secondary HA molecules
      aggregate in solution to form tertiary network structures. Adsorption from
      tertiary structure was reduced because strong interactions between the HA
      molecules limited the availability of hydrophobic patches for adsorption of HA
      onto FP. The influence of preparation variables on adsorption was also related to
      the availability of hydrophobic patches for adsorption.

PMID- 17207593
TI  - Prevention of hepatic oxidative injury by Xiao-Chen-Chi-Tang in mice.
AB  - The three purgative Cheng-Chi-Tang decoctions (CCTDs) including Ta-Cheng-Chi-Tang
      (TCCT), Xiao-Chen-Chi-Tang (XCCT), and Tiao-Wei-Chen-Chi-Tang (TWCCT) are used
      for treating gastrointestinal disorders, including liver diseases in traditional
      Chinese medicine. However, the underlying mechanisms as liver disease remedies
      are far from fully clarified. The objective of the study is to investigate and
      compare the antioxidant activity of the three purgative CCTDs in order to
      delineate their hepatic protective potential and mechanism. Antioxidant activity
      measured with the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging test
      indicated XCCT as the most potent preparation (IC(50) 8.94 microg/ml). In tert
      butylhydroperoxide (TBH, 50mM)-induced lipid peroxidation in ICR mice liver
      homogenates, XCCT also showed stronger and dose-dependent inhibitory activity
      against TBH-induced malondialdehyde (MDA, a marker of lipid peroxidation)
      production (IC(50) 53.66 microg/ml). In addition, XCCT showed dose-dependent
      protective effect against TBH-induced cytotoxicity in normal human Chung liver
      cells Furthermore, in carbon tetrachloride (CCl(4))-induced acute liver injury
      model, mice pretreated with 0.2g/kg and 0.4 g/kg of XCCT extracts showed a
      decrease of 59.8 and 43.1% in serum glutamic oxaloactetic transaminase (GOT)
      level, 51.4 and 52% in glutamic pyruvate transaminase (GPT) level, along with a
      reduction of 31 and 15% in MDA level, respectively, similar to the effects
      exerted by silymarin. XCCT pretreated mice also showed milder necrotic changes in
      the microscopic picture of the liver. The results suggest that XCCT has
      significant antioxidant activity and hepatic protection potential.

PMID- 17207594
TI  - Size influence on shape of handwritten characters loops.
AB  - In the practice of forensic handwriting experts, the size of the writing on a
      questioned document may be different from that of known samples. In this study,
      the hypothesis of shape invariance of handwritten closed loops across size
      increasing was tested. A Fourier methodology was applied to 2325 small letters
      (591 a loops, 547 d loops, 596 o loops and 591 q loops) and 692 enlarged letters
      (162 a loops, 173 d loops, 173 o loops and 184 q loops), in a population of 13
      writers who were asked to write letters in their usual size and about three times
      larger. Most of the writers presented similar modifications when increasing the
      size of the loops; they produced enlarged loops significantly more round and less
      slanted towards the right or the left. Furthermore, a discrimination was
      demonstrated between the writers on the basis of the enlarged loops, with a
      correct classification rate superior to 90%, whatever the letter (a, d, o or q).
      A classification of the enlarged loops in their corresponding writer was then
      possible. On the contrary, when comparing the enlarged loops to the small ones,
      almost one half of the enlarged loops were allocated to a wrong writer. Shape
      invariance was thus not supported for this particular application. Consequently,
      when comparing documents with a different writing size, differences in loops
      shape should be interpreted cautiously because they may be due to a different
      writer, but they may also be due to an enlargement of the loops. Therefore,
      reference material of similar writing size to that of the questioned writing
      should be requested for the comparison of handwritten loops.

PMID- 17207595
TI  - Attention and executive functions profile in drug naive ADHD subtypes.
AB  - Attention deficit hyperactivity disorder (ADHD) has been associated with
      executive functioning and sustained and divided attention deficits. In order to
      clarify the questions on neurocognitive impairment in ADHD, we investigated the
      presence of specific executive functions (EFs) and attention deficit patterns in
      ADHD clinical subtypes. 50 patients with ADHD and 44 controls were evaluated. All
      subjects were boys and performed a clinical-psychopathological and
      neuropsychological battery. Five main domains of EFs and attention were studied.
      Executive functions-related neurocognitive abilities were used as control tasks.
      ADHD patients, inattentive and combined subtypes differ from controls on response
      inhibition, divided attention, phonological, and visual object working memory and
      on variability of reaction times measured with CPT. Comparison of ADHD subtypes,
      in five main domains of EFs, did not show evidence of different executive
      functioning profiles. Response inhibition can predict performance on working
      memory tests but it cannot predict performance on divided attention/set shifting
      and on sustained attention. ADHD boys exhibit a selective impairment on executive
      functions and attention tasks. These data suggest the involvement of partially
      independent neural circuits which control inhibition and divided attention in
      ADHD. Since right prefrontal cortex seems to be crucial in controlling response
      inhibition, while left dorsolateral prefrontal cortex seems important in
      modulating divided attention, these areas are deputated to be involved in the
      pathogenesis of neuropsychological deficits in ADHD subtypes. In addition, this
      study candidates the impairment in phonological and visual-object working memory
      as a possible neuropsychological trait in ADHD males with inattentive or combined
      subtypes.

PMID- 17207597
TI  - Aicardi syndrome with favorable outcome: case report and review.
AB  - Aicardi syndrome is a congenital disorder characterized by severe psychomotor
      retardation, corpus callosum agenesis, chorioretinal lacunae, and early-onset
      infantile spasms. The prognosis is generally poor for children with the classical
      form. We report a peculiar case of Aicardi syndrome characterized by corpus
      callosum hypoplasia, brain malformations with subependymal heterotopias,
      extensive chorioretinal lacunae, seizures, and normal cognitive functions.
      Therefore, the clinical picture of the syndrome is broader than originally
      described. Cognitive disorders should not be considered inevitable and the
      prognosis not ineludibly poor.

PMID- 17207598
TI  - The dnaJ gene as a novel phylogenetic marker for identification of Vibrio
      species.
AB  - The utility of the dnaJ gene for identifying Vibrio species was investigated by
      analyzing dnaJ sequences of 57 type strains and 22 clinical strains and comparing
      sequence homologies with those of the 16S rDNA gene and other housekeeping genes
      (recA, rpoA, hsp60). Among the 57 Vibrio species, the mean sequence similarity of
      the dnaJ gene (77.9%) was significantly less than that of the 16S rDNA gene
      (97.2%), indicating a high discriminatory power of the dnaJ gene. Most Vibrio
      species were, therefore, differentiated well by dnaJ sequence analysis. Compared
      to other housekeeping genes, the dnaJ gene showed better resolution than recA or
      rpoA for differentiating Vibrio coralliilyticus from Vibrio neptunius and Vibrio
      harveyi from Vibrio rotiferianus. Among the clinical strains, all 22 human
      pathogenic strains, including an atypical strain, were correctly identified by
      the dnaJ sequence. Our findings suggest that analysis of the dnaJ gene sequence
      can be used as a new tool for the identification of Vibrio species.

PMID- 17207599
TI  - Supplementary biochemical tests useful for the differentiation of oxidase
      positive staphylococci.
AB  - Differentiation of the oxidase positive staphylococci, Staphylococcus sciuri,
      Staphylococcus lentus, Staphylococcus vitulinus and Staphylococcus fleurettii,
      based on tributyrin, urease, caseinase, gelatinase and DNase activity is
      described. These tests may be used for preliminary identification of oxidase
      positive isolates of staphylococci resulting in more accurate identification of
      these species.

PMID- 17207600
TI  - Application of lactate amperometric sol-gel biosensor to sequential injection
      determination of L-lactate.
AB  - This work describes the construction and evaluation of lactate sol-gel biosensors
      to accomplish the determination of lactate in pharmaceutical products. Lactate
      oxidase was incorporated in a porous sol-gel film placed onto a platinum-based
      electrode. Acid and basic catalysis were assessed. When coupled to a sequential
      injection system (SIA) the biosensor, based on (3-aminopropyl)trimethoxysilane, 2
      (3,4-epoxycyclohexyl)ethyl-trimethoxysilane, deionised water, polyethylene glycol
      6000 and acid catalyst, presented a range of linearity of 5x10(-5) to 5x10(-3)M.
      The analytical usefulness of the developed biosensor was evaluated through
      analysis of commercial pharmaceutical products containing lactate with a sampling
      rate of 40 samples h(-1). The enzyme remained active for at least 30 days,
      enabling about 700 determinations without sensitivity decrease.

PMID- 17207601
TI  - Structure elucidation of a novel analogue of sildenafil detected as an adulterant
      in an herbal dietary supplement.
AB  - A new analogue of sildenafil was detected in an herbal dietary supplement, which
      was sold over the internet and promoted as a product for the enhancement of
      sexual performance. The structure of the compound was established using LC-MS, UV
      spectroscopy, MS-MS, and NMR. In addition, the compound was cleaved at its
      sulfonamide S-N bond yielding a sulfonic acid and an amine, which were
      independently characterized using LC-MS, GC-MS, and derivatization. The compound,
      named methisosildenafil, is a novel synthetic analogue of sildenafil in which the
      N-methylpiperazine moiety has been replaced with 2,6-dimethylpiperazine.

PMID- 17207602
TI  - Isolation and characterization of some potential impurities in ropinirole
      hydrochloride.
AB  - Three impurities in ropinirole hydrochloride drug substance at levels
      approximately 0.06-0.15% were detected by reverse-phase high performance liquid
      chromatography (HPLC). These impurities were isolated from the drug substance.
      These impurities were analyzed using reverse-phase HPLC. Based on the spectral
      data (IR, NMR and MS), structures of these impurities were characterized as 4-[2
      (propylamino) ethyl]-1,3-dihydro-2H-indol-2-one hydrochloride (impurity-A), 5-[2
      (diropylamino) ethyl]-1,4-dihydro-3H-benzoxazin-3-one hydrochloride (impurity-B)
      and 4-[2-(diropylamino) ethyl]-1H-indol-2,3-dione hydrochloride (impurity-C).
      Synthesis of these impurities is discussed.

PMID- 17207603
TI  - Gene expression during seed maturation in Brassica napus in relation to the
      induction of secondary dormancy.
AB  - Gene expression in two cultivars of Brassica napus (AC Excel and DH12075) has
      been compared at the full-size embryo, desiccation, and mature stages of seed
      development. Seed of these cultivars differ in their potential to exhibit
      secondary dormancy following environmental stress; Excel has high potential and
      DH12075 has low potential. A majority of genes were down-regulated during
      maturation in both cultivars but a significant number of differences in gene
      expression between the cultivars were apparent in the transition from full-size
      embryo to mature seed. However, most differences were apparent in the desiccation
      stage and some of the differences were in genes related to signaling processes
      and protein biosynthesis. We suggest that the propensity of Brassica seeds to
      manifest secondary dormancy may be determined by changes in gene expression that
      occur during late seed development.

PMID- 17207604
TI  - Maple syrup urine disease: diffusion MRI, and proton MR spectroscopy findings.
AB  - A 7-month-old boy is reported with acute metabolic crisis of maple syrup urine
      disease. A reversible intramyelinic type of edema was noted by diffusion MRI
      which completely resolved in 3 months in accordance with good clinical outcome.
      Proton MR spectroscopy revealed decreased NAA, and presence of methyl resonances
      of branched chain amino acids at 0.9 ppm, and lactic acid in the initial
      examination. After 3 months, NAA returned to normal, and lactic acid disappeared.
      The methyl resonance of branched chain amino acids, however, remained.

PMID- 17207605
TI  - Novel animal models for Sjogren's syndrome: expression and transfer of salivary
      gland dysfunction from regulatory T cell-deficient mice.
AB  - IL-2 knockout (KO), IL-2Ralpha KO and scurfy mice lack the CD4+CD25+ regulatory T
      (Treg) cells and develop severe inflammation in multiple organs, although organs
      affected vary among these strains. We asked if salivary and lacrimal glands, the
      main organs affected in Sjogren's syndrome, are targeted in these strains. Severe
      lymphocyte and neutrophil infiltration in the salivary and lacrimal glands and a
      decrease in salivary secretory function were observed in IL-2 KO and IL-2Ralpha
      KO mice, but not in scurfy mice. Interestingly, transfer of lymph node cells from
      scurfy mice to RAG-1 KO recipients rapidly and effectively induced inflammation
      and loss of function in the salivary glands. Furthermore, we observed that daily
      LPS feeding in scurfy mice also induced inflammation in the salivary glands. Our
      study demonstrates several novel models for Sjogren's syndrome, including an
      adoptive transfer model that shows that scurfy mice have dormant salivary gland
      specific autoreactive lymphocytes that can be activated by certain environmental
      factors, such as those present in RAG-1 KO mice.

PMID- 17207606
TI  - Nitric oxide-evoked transient kinetics of cyclic GMP in vascular smooth muscle
      cells.
AB  - Cyclic-3',5'-guanosine monophosphate (cGMP) mediates the intracellular signaling
      cascade responsible for the nitric oxide (NO) initiated relaxation of vascular
      smooth muscle (VSM). However, the temporal dynamics, including the regulation of
      cGMP turnover, are largely unknown. Here we report new mechanistic insights into
      the kinetics of cGMP synthesis and hydrolysis in primary VSM cells by utilizing
      FRET-based cGMP-indicators [A. Honda, S.R. Adams, C.L. Sawyer, V. Lev-Ram, R.Y.
      Tsien, W.R. Dostmann, Proc. Natl. Acad. Sci. U S A 98 (5) (2001) 2437.]. First, 2
      (N,N-Diethylamino)-diazenolate 2-oxide (DEA/NO) and 2,2'
      (Hydroxynitrosohydrazono)-bis-ethanimine (DETA/NO) induced NO-concentration
      dependent, transient cGMP responses ("peaks") irrespective of their rates of NO
      release. The kinetic characteristics of these cGMP peaks were governed by the
      concerted action of the NO-sensitive guanylyl cyclase (GC) and phosphodiesterase
      type V (PDE5) as shown by their respective inhibition using 1H
      [1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and Sildenafil. These responses
      occurred in the presence of moderately elevated cGMP (5-15% FRET ratio), and thus
      activated PKG and phosphorylated PDE5, suggesting a prominent role for GC in the
      maintenance and termination of cGMP peaks. Furthermore, cGMP transients could be
      elicited repeatedly without apparent desensitization of GC or by suppression of
      cGMP via long-term PDE5 activity. These results demonstrate a continuous
      sensitivity of the NO/cGMP signaling system, inherent to the phasic nature of
      smooth muscle physiology.

PMID- 17207607
TI  - Concentration-response relationships as a basis for choice of the optimal
      endpoints of the antimicrobial effect: daptomycin and vancomycin pharmacodynamics
      with staphylococci in an in vitro dynamic model.
AB  - The abilities of different indices of bacterial killing to ensure reasonable
      concentration-response relationships have been compared only in studies in vitro
      with fluoroquinolones. To ascertain the relevance of conclusions drawn in these
      studies to other antibiotic classes, five widely used indices that reflect the
      rate of initial killing (time to reduce the initial inoculum 10- and 100-fold
      T(90%) and T(99%), respectively), the extent of killing (minimal number of
      surviving organisms-N(min)), and the entire antimicrobial effect (number of
      surviving organisms (N(t)) at the time t close to the end of the observation
      period (48 h in most experiments), and area between the control growth curve and
      the time-kill curve from zero point to t-ABBC) were examined with daptomycin
      (DAP)- and vancomycin (VAN)-exposed Staphylococcus aureus. To compare the
      pharmacodynamics of DAP and VAN and examine different parameters, killing
      kinetics of differentially susceptible S. aureus were studied over a wide range
      of ratios of area under the curve (AUC) to MIC. Killing kinetics of two clinical
      isolates, S. aureus 866 (MIC(DAP) 0.35 mg/L and MIC(VAN) 0.70 mg/L) and S. aureus
      10 (MIC(DAP) 1.1mg/L and MIC(VAN) 1.3mg/L), were studied in an in vitro dynamic
      model that simulates human pharmacokinetics of DAP (as a single dose) and VAN (as
      two 12-h doses). Mono-exponential concentration decays were mimicked with half
      lives of 9h (DAP) and 6h (VAN) at AUC/MIC ratios varying from 33 to 1150 h.
      T(90%), T(99%) and N(t) (at t=48 h) exhibited loose, if any, correlations with
      log AUC/MIC. Both ABBC (a direct measure of the antimicrobial effect) and N(min)
      (an inverse measure of the effect) correlated well with log AUC/MIC (r(2)=0.8
      0.9). Based on the ABBC-log AUC/MIC relationships, the effects of DAP on S.
      aureus were predicted to be slightly greater than those of VAN at a given AUC/MIC
      ratio. The better abilities of ABBC and N(min) and the inability of T(90%) and
      T(99%) to provide reasonable AUC/MIC relationships with DAP and VAN support
      earlier findings reported with fluoroquinolones.

PMID- 17207608
TI  - Biochemical characterisation of the CTX-M-14 beta-lactamase.
AB  - Cefotaxime-resistant Escherichia coli TUM1121 was isolated from an abscess of an
      83-year-old patient. The CTX-M-14 gene was located on a 70 kb plasmid. The enzyme
      was purified and its activity was analysed. CTX-M-14 was poorly active against
      ceftazidime and aztreonam. Aztreonam behaved as a competitive inhibitor. Among
      the tested suicide substrates for class A beta-lactamases, sulbactam was a rather
      good substrate. Tazobactam and clavulanic acid behaved as inactivators. The
      interactions between clavulanic acid and CTX-M-14 were characterised by
      progressive inactivation of the beta-lactamase. Carbapenems such as imipenem,
      meropenem or doripenem did not behave as inactivators of CTX-M-14, however very
      small k(cat) values were observed. This result shows that CTX-M-14 is able to
      hydrolyse carbapenems.

PMID- 17207609
TI  - Caspofungin for the treatment of fungal infections: a systematic review of
      randomized controlled trials.
AB  - During the last decade, owing to the low effectiveness and high toxicity of older
      antifungals, new antifungal agents have been released to the market for the
      treatment of patients with fungal infections. Several randomized controlled
      trials (RCTs) have been designed to evaluate the effectiveness of caspofungin in
      comparison with other antifungal agents. This review was conducted to examine
      further the role of caspofungin in the treatment of patients with fungal, mainly
      Candida, infections. Two reviewers independently performed the literature search,
      study selection and data extraction from relevant RCTs. A total of six RCTs
      comparing caspofungin with amphotericin B (deoxycholate in four and liposomal in
      one RCT) or fluconazole (in one RCT), which studied a total of 1974 patients,
      were included in our review. Success of the applied treatment in the clinically
      evaluable patients was achieved in 496/943 (52.6%) of the caspofungin-treated
      patients and in 381/852 (44.7%) of the amphotericin B- and lipid amphotericin B
      treated patients. Discontinuation due to drug toxicity was significantly less
      common in patients receiving caspofungin than amphotericin B (odds ratio (OR)
      0.25, 95% confidence interval (CI) 0.07-0.85, random effects model). Development
      of nephrotoxicity, hypokalaemia and fever also occurred significantly less often
      with caspofungin than amphotericin B (OR 0.23, 95% CI 0.14-0.36, fixed effects
      model; OR 0.3, 95% CI 0.12-0.76, random effects model; and OR 0.26, 95% CI 0.08
      0.79, random effects model, respectively). No difference in mortality was noted.
      Caspofungin was associated with better clinical outcomes (higher cure and fewer
      adverse effects) than amphotericin B in the treatment of patients with fungal
      infections.

PMID- 17207610
TI  - Differences in the evolution of imipenem susceptibility among Klebsiella
      pneumoniae and Escherichia coli isolates during a 6-year period in a tertiary
      care hospital.
AB  - The evolution of imipenem disk-diffusion susceptibility results of 2652 strains
      of Klebsiella pneumoniae and 7596 Escherichia coli isolated during the period
      2000-2005 were analysed. Screening for production of metallo-beta-lactamases was
      performed using the EDTA-synergy method. The percentage rate of K. pneumoniae
      isolates having a zone diameter < or =25 mm increased from 20% in 2000 to 41% in
      2005, whereas the respective rate of isolates having a zone diameter > or =30 mm
      decreased from 48 to 23%. These changes were more evident during 2000-2002,
      followed in 2003 by the isolation of the first imipenem-resistant strains.
      Regarding E. coli, a similar decrease was observed (the rates of isolates having
      a zone diameter < or =25 mm and > or =30 mm changed from 7% and 68% in 2000, to
      32% and 36% in 2005, respectively) following the respective changes of K.
      pneumoniae. A total of 20 K. pneumoniae strains, but no E. coli, were confirmed
      as metallo-beta-lactamase producers. In conclusion, a decrease of the imipenem
      susceptibility prior to the isolation of the first resistant strains in a
      tertiary care hospital was detected, as well as differences in this decrease
      between the two species. These findings indicate that monitoring of the evolution
      of imipenem susceptibility in real-time may help in unveiling forthcoming
      resistance and in implementing the appropriate diagnostic techniques.

PMID- 17207611
TI  - Further investigation of the mechanism of Doxorubicin release from P105 micelles
      using kinetic models.
AB  - The kinetics of the release of Doxorubicin from Pluronic P105 micelles during
      ultrasonication and its subsequent re-encapsulation upon cessation of insonation
      were investigated. Four mechanisms are proposed to explain the acoustically
      triggered Doxorubicin (Dox) release and re-encapsulation from Pluronic P105
      micelles. The four mechanisms are: micelle destruction; destruction of cavitating
      nuclei; reassembly of micelles, and the re-encapsulation of Dox. The first
      mechanism, the destruction of micelles during insonation, causes the release of
      Dox into solution. The micelles are destroyed because of cavitation events
      produced by collapsing nuclei, or bubbles in the insonated solution. The second
      mechanism, the slow destruction of cavitating nuclei, results in a slow partial
      recovery phase, when a small amount of Dox is re-encapsulated. The third and
      fourth mechanisms, the reassembly of micelles and the re-encapsulatin of Dox, are
      independent of ultrasound. These two mechanism are responsible for maintaining
      the drug release at a partial level, and for recovery after insonation ceases. A
      normal distribution was used to describe micellar size. Parameters for the model
      were determined based upon the best observed fit to experimental data. The
      resulting model provides a good approximation to experimental data for the
      release of Dox from Pluronic P105 micelles.

PMID- 17207612
TI  - Interfacial properties and fluorescence of a coagulating protein extracted from
      Moringa oleifera seeds and its interaction with sodium dodecyl sulphate.
AB  - The surfactant behaviour of aqueous coagulating protein extracted from Moringa
      oleifera seeds has been investigated by surface tension measurements. The
      interaction of the coagulant protein with an anionic surfactant sodium dodecyl
      sulphate (SDS) has been monitored by surface tension and intrinsic protein
      fluorescence measurements. The extracted protein shows some weak surface activity
      at low concentrations. To achieve maximum surface activity (i.e. maximum
      reduction in surface tension of water), substantially higher concentrations of
      protein are required. The coagulant protein-SDS interaction scheme did not
      exhibit the behaviour of weakly interacting polymer-surfactant systems and the
      SDS interacts in a monomeric form with the protein. The association process of
      SDS with the coagulant protein is supported by protein fluorescence measurements.
      SDS has an effect on the fluorescence of the coagulant protein indicating that
      the local environment of tryptophan in the protein changes as SDS concentration
      below its critical micelle concentration is increased. These results have led us
      to the conclusions that: (1) the protein extracted from M. oleifera seeds has
      significant surfactant behaviour; (2) the coagulant protein interacts strongly
      with SDS and the protein might have specific binding sites for SDS; (3) there is
      formation of protein-SDS complex.

PMID- 17207613
TI  - [Subacute cutaneous lupus erythematosus in childhood: a case report].
AB  - Subacute cutaneous lupus erythematosus is extremely rare in childhood. We report
      the case of a 7 year-old girl who presented annular erythematous infiltrated
      lesions on sun exposed areas since the age of 2 months. Histopathologic
      examination showed orthohyperkeratosis, epidermal atrophy, widespread hydropic
      degeneration of epidermal basal cell layer, and a dermal lymphohistiocytic
      infiltrate. The lupus band test was negative. The immunological investigations
      (antinuclear antibodies) were negative. Treatment with antimalarials, topical
      steroids and sun protection allowed clearance of the cutaneous lesions. Lesions
      relapsed after antimalarials discontinuation and sun exposure. Four years later,
      at the age of 11, the antinuclear antibodies became positive. The diagnosis of
      subacute cutaneous lupus erythematosus is based on the clinical aspect of
      lesions, topography, histological finding, evolution and immunological profile of
      the patient.

PMID- 17207614
TI  - Linamarase activities in Bacillus spp. responsible for thermophilic aerobic
      digestion of agricultural wastes for animal nutrition.
AB  - Thermophilic Bacillus spp. isolated from thermophilic aerobic digestion (TAD) of
      model agricultural slurry were screened for ability to secret linamarase activity
      and degrade linamarin, a cyanogenic glycoside toxin abundant in cassava.
      Screening was performed by both linamarin - picrate assay and by p-nitrophenyl
      beta-D-glucoside (PNPG) degradation, and results of both assays were related.
      Linamarase positive isolates were identified as Bacillus coagulans, Bacillus
      licheniformis and Bacillus stearothermophilus. Enzyme production was growth
      related and peak production was reached in 48 h in B. coagulans and 36 h in B.
      stearothermophilus. B. coagulans produced over 40 times greater activity than B.
      stearothermophilus. Enzyme productivity in shake flask was not strictly related
      to screening assay result. Crude enzyme of B. coagulans was optimally active at
      75 degrees C while that of B. stearothermophilus was optimally active at 80
      degrees C and both had optimum activity at pH 8.0. The thermophilic and
      neutrophilic- to marginally alkaline activity of the crude enzymes could be very
      useful in the detoxification and reprocessing of cyanogens containing cassava
      wastes by TAD for use in animal nutrition.

PMID- 17207615
TI  - Leachability and metal-binding capacity in ageing landfill material.
AB  - In order to study the stability of landfilled heavy metals, landfill material
      from a combined household and industrial waste landfill was aerated for 14 months
      to simulate the natural ageing processes as air slowly begins to penetrate the
      landfill mass. During aeration, the pH of the landfill material decreased from
      around 8.6 to 8.1 and the carbon content also decreased. In order to investigate
      the possible fate of metals in ageing landfills, a four-stage sequential
      extraction technique was applied. The ability of the materials to bind metal ions
      by electrostatic attractions and to form stronger complexes was studied
      separately. The amount of exchangeable cations, the capacity to bind metal ions
      by electrostatic attraction and the capacity of the landfill material to complex
      copper ions were increased by the aeration process. However, results from the
      sequential analysis showed an increased solubility of sulphur and some metals
      (Cd, Co, Cu, Ni and Zn). Equilibrium speciation models (Medusa) indicated that
      the organic matter deposit had a significant capacity to bind metal ions provided
      that pH was sufficiently high. However, as carbonates are consumed over time, the
      risk for metal mobility increases. Therefore, the landfills can become an
      environmental risk, depending on variations in the solubility of metal ions due
      to changes in pH, redox status and the availability of organic material.

PMID- 17207616
TI  - Recycling of waste PET into useful textile auxiliaries.
AB  - Polyethylene terephthalate (PET) waste fibers were initially depolymerized using
      a glycolysis route in the presence of sodium sulfate as a catalyst, which is a
      commonly used chemical and ecofriendly as compared to heavy metal catalysts. Good
      yield of the pure monomer bis(2-hydroxyethylene terephthalate) (BHET) was
      obtained. Further, to attempt its reuse, the purified BHET was converted to
      different fatty amide derivatives to obtain quaternary ammonium compounds that
      have a potential for use as softener in the textile finishing process. The
      products were characterized by infrared spectroscopy. Application of these
      synthesized compounds was carried out on cotton fabric; they were evaluated for
      performance and were found to give good results. The chemicals used during
      depolymerization and reuse of PET are inexpensive and comparatively less harmful
      to the environment, and thus offer advantages in the chemical recycling of
      polyester waste fibers.

PMID- 17207617
TI  - Differential expression of prohibitin is correlated with dual action of Vitamin D
      as a proliferative and antiproliferative hormone in breast epithelial cells.
AB  - Our previous microarray analysis showed that N-methyl-N-nitrosourea (MNU)
      transformed MCF12F breast epithelial cells exhibited upregulation of several
      genes, including prohibitin, which was reversed by 1alpha-hydroxyvitamin D(5)
      (1alpha(OH)D(5)) treatment. The in silico screening for putative transcription
      factor binding sites identified two VDR/RXR binding sites in the 1kb promoter
      region of prohibitin. Other binding sites for EGR and GR which are also Vitamin D
      target genes were identified in this region, indicating that prohibitin is a
      potential target gene for Vitamin D. The combination of multiple binding sites
      also provides a basis for a possible dual regulation of prohibitin by Vitamin D.
      Prohibitin upregulation by 1alpha(OH)D(5) treatment at both transcription and
      translation level was observed in Vitamin D sensitive BT474 breast cancer cells,
      in which 1alpha(OH)D(5) significantly inhibited cell proliferation in normal
      culture condition. On the other hand, prohibitin down-regulation accompanied with
      Vitamin D mediated maintenance of proliferation of breast epithelial cells was
      observed under stressed condition. These results demonstrated that Vitamin D
      mediated antiproliferative activity in unstressed condition and growth
      maintaining activity under stressed condition involve differential expression of
      prohibitin.

PMID- 17207618
TI  - Electrochemical treatment of anaerobic digestion effluent using a Ti/Pt-IrO2
      electrode.
AB  - Electrochemical treatment of the anaerobic digestion effluents using a Ti/Pt
      IrO(2) electrode was evaluated in this study. The effects of electric current,
      NaCl dosage, and initial pH on ammonia, nitrate, total organic carbon (TOC),
      inorganic carbon (IC), final pH, and turbidity variations were studied in a
      series of batch experiments. It was found that the electric current and NaCl
      dosage had a considerably larger effect on the oxidization of ammonia; this was
      less for the effect of the initial pH. In addition, electroflotation was the main
      mechanism for turbidity, TOC, and IC removals. Further, the IC removal was mainly
      affected by the pH of wastewater. The electrochemical treatment using Ti/Pt
      IrO(2) electrode without pretreatment was feasible for the anaerobic digestion
      effluent.

PMID- 17207619
TI  - Evaluation of culture conditions for cellulase production by two Trichoderma
      reesei mutants under solid-state fermentation conditions.
AB  - Response surface methodology (RSM) was used to evaluate the effects of
      fermentation parameters for cellulase production by Trichoderma reesei QM9414 and
      T. reesei MCG77 in solid-state fermentation using rice bran as substrate. Initial
      pH, moisture content and temperature were optimized using filter paper activity
      (FPA) as response. Statistical analysis of the results for T. reesei QM9414
      showed that only moisture content had significant effect on cellulase activity
      and had a linear effect on enzyme activity (maximum enzyme activities were
      obtained at 70% moisture content). The results for T. reesei MCG77 showed that
      temperature and moisture content were the most significant parameters for
      cellulase activity. The optimum cellulase production was in the temperature range
      of 25-30 degrees C and moisture content between 55% and 70%. After the
      optimization, the FPA in T. reesei MCG77 was increased by 2.5 folds compared to
      that of T. reesei QM9414.

PMID- 17207620
TI  - Solid-state cultures of Fusarium oxysporum transform aromatic components of olive
      mill dry residue and reduce its phytotoxicity.
AB  - The present study mainly investigated the ability of solid-state cultures of the
      non-pathogenic Fusarium oxysporum strain BAFC 738 to transform aromatic
      components to reduce the phytotoxicity in olive-mill dry residue (DOR), the waste
      from the two-phase manufacturing process. Lignin, hemicellulose, fats and water
      soluble extractives contents of DOR colonized by the fungus for 20 weeks were
      reduced by 16%, 25%, 71% and 13%, respectively, while the cellulose content
      increased by 25%. In addition, the ethyl acetate-extractable phenolic fraction of
      the waste was reduced by 65%. However, mass-balance ultra-filtration and size
      exclusion chromatography experiments suggested that the apparent removal of that
      fraction, mainly including 2-(3,4-dihydroxyphenyl)ethyl alcohol and 2-(4
      hydroxyphenyl)ethyl alcohol, was due to polymerization. Mn-peroxidase and Mn
      independent peroxidase activities were found in F. oxysporum solid-state
      cultures, while laccase and aryl alcohol oxidase activities were not detected.
      Tests performed with seedlings of tomato (Lycopersicum esculentum L.), soybean
      (Glycine maximum Merr.), and alfalfa (Medicago sativa L.) grown on soils
      containing 6% (w/w) of bioconverted DOR (kg soil)(-1) showed that the waste's
      phytotoxicity was removed by 20 weeks-old fungal cultures. By contrast, the same
      material exhibited a high residual toxicity towards lettuce (Lactuca sativa L.).

PMID- 17207621
TI  - Selection of lactic yeast producing glucosylceramide from cheese whey.
AB  - From 2150 isolates from raw milk and milk products, yeast strains were surveyed
      to produce glucosylceramide from cheese whey. Most of the 54 strains that had
      accumulated a detectable amount of glucosylceramide were identified as
      Kluyveromyces lactis var. lactis. The cells of K. lactis var. lactis strain M-11
      derived from domestic raw milk accumulated glucosylceramide 2.5-fold higher than
      K. lactis var. lactis NBRC 1267, the reference strain selected from the culture
      collections. Strain M-16 of K. lactis var. lactis derived from the same origin
      was found to synthesize a considerable amount of steryl glucoside in addition to
      glucosylceramide. Sequence analysis of ribosomal DNA intergenic spacer two
      regions revealed that strains M-11 and M-16 were diverged from a type strain of
      K. lactis var. lactis in the same species.

PMID- 17207622
TI  - Activated sludge treatment of a xenobiotic with or without a biogenic substrate
      during start-up and shocks.
AB  - Lab-scale continuous flow activated sludge systems that were acclimated to 2,4
      dichlorphenoxyacetic acid (2,4-D) under sole 2,4-D influent and without sludge
      wastage, were able to maintain successful 2,4-D treatment when both 2,4-D and a
      biogenic substrate were fed and the systems operated with finite mean cell
      residence times (theta(c)). When the systems were fed dual 2,4-D and biogenic
      substrates and operated with finite theta(c) from the start, treatment of 2,4-D
      fluctuated noticeably long after acclimation. At the reintroduction of 2,4-D
      after its absence from the influent for a period of time (2,4-D shock), the
      systems under both the sole and dual substrate conditions suffered similar
      treatment losses; the extent of treatment losses was related to the length of 2,4
      D absence time. When shocked, systems with sole 2,4-D influent had a slight
      advantage over dual substrates by showing a faster recovery from shocks with the
      help of re-acclimation.

PMID- 17207623
TI  - Cost-utility of adjuvant hormone therapies with aromatase inhibitors in post
      menopausal women with breast cancer: upfront anastrozole, sequential tamoxifen
      exemestane and extended tamoxifen-letrozole.
AB  - This evaluation adapts a previous Canadian analysis of upfront and sequential
      adjuvant AI strategies in postmenopausal women with breast cancer to a Belgian
      perspective and includes an extended aromatase inhibitor (AI) strategy. A Markov
      model calculated monthly costs and outcomes in a hypothetical cohort of
      postmenopausal women with early-stage breast cancer. Baseline event rates and
      hazard ratios were derived from the Arimidex, Tamoxifen Alone or in Combination
      trial, International Exemestane Study and MA.17 trials. The analysis took a
      Belgian healthcare payer perspective with a 20-year time horizon. Costs and
      outcomes were discounted by 3%. Costs are in 2005 Euros. The cost-utility of all
      three strategies was favourable (<30,000 euros per QALY gained). Based on
      indirect comparisons using tamoxifen (TAM) alone as a common comparator,
      sequential TAM-AI was less costly and more effective than upfront or extended
      strategies. All three AI strategies were cost-effective alternatives to TAM
      alone, but sequential TAM-AI appears to be the economically preferred strategy.

PMID- 17207624
TI  - Y-family DNA polymerases in Escherichia coli.
AB  - The observation that mutations in the Escherichia coli genes umuC+ and umuD+
      abolish mutagenesis induced by UV light strongly supported the counterintuitive
      notion that such mutagenesis is an active rather than passive process. Genetic
      and biochemical studies have revealed that umuC+ and its homolog dinB+ encode
      novel DNA polymerases with the ability to catalyze synthesis past DNA lesions
      that otherwise stall replication--a process termed translesion synthesis (TLS).
      Similar polymerases have been identified in nearly all organisms, constituting a
      new enzyme superfamily. Although typically viewed as unfaithful copiers of DNA,
      recent studies suggest that certain TLS polymerases can perform proficient and
      moderately accurate bypass of particular types of DNA damage. Moreover, various
      cellular factors can modulate their activity and mutagenic potential.

PMID- 17207625
TI  - Unique SARS-CoV protein nsp1: bioinformatics, biochemistry and potential effects
      on virulence.
AB  - Viruses have evolved a myriad of strategies for promoting viral replication,
      survival and spread. Sequence analysis of the Severe Acute Respiratory Syndrome
      Coronavirus (SARS-CoV) genome predicts several proteins that are unique to SARS
      CoV. The search to understand the high virulence of SARS-CoV compared with
      related coronaviruses, which cause lesser respiratory illnesses, has recently
      focused on the unique nsp1 protein of SARS-CoV and suggests evolution of a
      possible new virulence mechanism in coronaviruses. The SARS-CoV nsp1 protein
      increases cellular RNA degradation and thus might facilitate SARS-CoV replication
      or block immune responses.

PMID- 17207626
TI  - Experimental evaluation of the biomechanical performances of a PMMA-based knee
      spacer.
AB  - Infection of knee prostheses is still one of the major concerns of the
      reliability over time of these implantable devices. The preferred treatment of
      this condition has turned out to be the use of a knee spacer in a two-stage
      reimplantation technique. The advantages of this technique associated with the
      use of a mobile spacer lies both in the possibility for the patient to move
      during the interim period, thus decreasing the risk of muscle contracture due to
      immobilisation, as well as in the ability to release antibiotics directly to the
      site of infection. The evaluation of the biomechanical properties of new mobile
      spacers preformed in three different sizes has been carried out subjecting the
      spacers to i) cyclic tests on a knee simulator for 500,000 walking cycles, ii)
      constraint tests in medio-lateral, antero-posterior and internal-external
      directions, iii) fatigue tests on the tibial tray. Particular attention was
      addressed to the evaluation of the mechanical resistance of the devices, to the
      quantity of wear debris produced during the tests and to the extent that such
      debris was influenced by the test parameters and geometrical dimensions of the
      spacers themselves. Results showed no sign of failure for any of the tested
      spacers, the constraint and fatigue behaviours were similar to those shown by a
      total knee prosthesis and the amount of debris turned out to be directly
      correlated to the size of the devices: in conclusion, the devices showed a good
      level of mechanical performance and, consequently, a sufficiently high degree of
      suitability for clinical use.

PMID- 17207627
TI  - Environmental radioactivity measurements in Kastamonu region of northern Turkey.
AB  - Located in the north-western part of Turkey, the province of Kastamonu has lately
      been receiving national attention because of its cultural and touristic
      attractions. This study assesses the environmental radioactivity levels of the
      region through measurements of indoor radon concentrations and indoor/outdoor
      gamma absorbed dose in air and radionuclide activities in surface soil and
      drinking water. The indoor (222)Rn activity concentration was found to be 98.4
      Bq/m(3) equivalent to an annual effective dose of 2.48 mSv. The indoor and
      outdoor gamma absorbed doses were measured as 54.81 and 48.03 nGy/h,
      respectively, corresponding to a total gamma radiation level (of terrestrial and
      cosmic origin) of 0.33 mSv/y. The activity concentrations in the soil samples
      collected from the study area were determined as 32.93, 27.17, 431.43 Bq/kg for
      the natural radionuclides (238)U, (232)Th and (40)K, respectively, and 8.02 Bq/kg
      for the fission product (137)Cs. These natural radioactivity sources result in a
      terrestrial gamma level of 60 microSv/y. The water samples collected from the
      region carry an average of 0.0089 Bq/l of gross alpha and 0.271 Bq/l of gross
      beta activities which together cause an annual effective dose of 1.83 microSv.
      The measurement results obtained in this study indicate that the region has a
      background radiation level that is within the natural limits and shows no
      significant departure from the other parts of the country.

PMID- 17207628
TI  - The cell-specific expression of metalloproteinase-disintegrins (ADAMs) in
      inflammatory myopathies.
AB  - Inflammatory cell invasion and cytokine activation are important steps in the
      pathogenesis of immune-mediated diseases of muscle. Metalloproteinase
      disintegrins (ADAMs) are considered to play a critical role in leukocyte
      migration by promoting cellular adhesion, cleavage of molecules of the
      extracellular matrix and shedding of membrane bound cytokines. Here, we report
      the expression patterns of ADAM8, ADAM9, ADAM10, ADAM12, ADAM17 and ADAM19 in
      cultured human myoblasts and peripheral blood mononuclear cells (PBMCs) in vitro,
      as well as in biopsies from patients suffering from polymyositis (PM),
      dermatomyositis (DM), inclusion body myositis (IBM) and non-inflammatory
      controls. We observed an in vitro downregulation of the RNAs of ADAM10, ADAM17
      and ADAM19 in myoblasts after stimulation with various pro- and anti-inflammatory
      mediators, whereas in PBMCs an RNA upregulation of ADAM9, ADAM10, ADAM17 and
      ADAM19 was detectable under identical conditions. In human muscle biopsies,
      invading CD3+ T lymphocytes expressed ADAM17 and ADAM19, whereas macrophages co
      localized to ADAM8, as detected by immunohistochemistry. Transfection of PBMCs
      with ADAM19 single interfering RNA and incubation with a metalloproteinase
      inhibitor suggest proteolytic activity of ADAM19 and involvement in the shedding
      of tumor necrosis factor-alpha. No differences in the cellular expression
      profiles between PM, DM and IBM were found, whereas the sections from non
      inflammatory controls did not reveal any positive immunoreactivity for ADAMs,
      except for ADAM10, which is localized exclusively to muscle fibres. Our results
      suggest that certain ADAMs are expressed by specific cell populations during the
      genesis of immune-mediated diseases of human muscle.

PMID- 17207629
TI  - Reduced GABAB receptor subunit expression and paired-pulse depression in a
      genetic model of absence seizures.
AB  - Neocortical networks play a major role in the genesis of generalized spike-and
      wave (SW) discharges associated with absence seizures in humans and in animal
      models, including genetically predisposed WAG/Rij rats. Here, we tested the
      hypothesis that alterations in GABA(B) receptors contribute to neocortical
      hyperexcitability in these animals. By using Real-Time PCR we found that mRNA
      levels for most GABA(B(1)) subunits are diminished in epileptic WAG/Rij neocortex
      as compared with age-matched non-epileptic controls (NEC), whereas GABA(B(2))
      mRNA is unchanged. Next, we investigated the cellular distribution of GABA(B(1))
      and GABA(B(2)) subunits by confocal microscopy and discovered that GABA(B(1))
      subunits fail to localize in the distal dendrites of WAG/Rij neocortical
      pyramidal cells. Intracellular recordings from neocortical cells in an in vitro
      slice preparation demonstrated reduced paired-pulse depression of
      pharmacologically isolated excitatory and inhibitory responses in epileptic
      WAG/Rij rats as compared with NECs; moreover, paired-pulse depression in NEC
      slices was diminished by a GABA(B) receptor antagonist to a greater extent than
      in WAG/Rij rats further suggesting GABA(B) receptor dysfunction. In conclusion,
      our data identify changes in GABA(B) receptor subunit expression and distribution
      along with decreased paired-pulse depression in epileptic WAG/Rij rat neocortex.
      We propose that these alterations may contribute to neocortical hyperexcitability
      and thus to SW generation in absence epilepsy.

PMID- 17207630
TI  - Intracellular pH regulates amyloid precursor protein intracellular domain
      accumulation.
AB  - The amyloid precursor protein (APP) metabolism is central to pathogenesis of
      Alzheimer's disease (AD). Parenchymal amyloid deposits, a neuropathological
      hallmark of AD, are composed of amyloid-beta peptides (Abeta). Abeta derives from
      the amyloid precursor protein (APP) by sequential cleavages by beta- and gamma
      secretases. Gamma-secretase cleavage releases the APP intracellular domain
      (AICD), suggested to mediate a nuclear signaling. Physiologically, AICD is seldom
      detected and thus supposed to be rapidly degraded. The mechanisms responsible of
      its degradation remain unknown. We used a pharmacological approach and showed
      that several alkalizing drugs induce the accumulation of AICD in neuroblastoma
      SY5Y cell lines stably expressing APP constructs. Moreover, alkalizing drugs
      induce AICD accumulation in naive SY5Y, HEK and COS cells. This accumulation is
      not mediated by the proteasome or metallopeptidases and is not the result of an
      increased gamma-secretase activity since the gamma-secretase cleavage of Notch1
      and N-Cadherin is not affected by alkalizing drug treatments. Altogether, our
      data demonstrate for the first time that alkalizing drugs induce the accumulation
      of AICD, a mechanism likely mediated by the endosome/lysosome pathway.

PMID- 17207631
TI  - Anti-apoptotic signaling and failure of apoptosis in the ischemic rat
      hippocampus.
AB  - Several anti-apoptotic proteins are induced in CA1 neurons after transient
      forebrain ischemia (TFI), but fail to protect the majority of these cells from
      demise. Correlating cell death morphologies (apoptosis-like and necrosis-like
      death) with immunohistochemistry (IHC), we investigated whether anti-apoptosis
      contributes to survival, compromises apoptosis effector functions and/or delays
      death in CA1 neurons 1-7 days after TFI. As surrogate markers for bioenergetic
      failure, the IHC of respiratory chain complex (RCC) subunits was investigated.
      Dentate granule cell (DGC) apoptosis following colchicine injection severed as a
      reference for classical apoptosis. Heat shock protein 70 (Hsp70), neuronal
      apoptosis inhibitory protein (NAIP) and manganese superoxide dismutase (MnSOD)
      were upregulated in the majority of intact CA1 neurons paralleling the occurrence
      of CA1 neuronal death (days 3-7) as well as in a proportion of apoptosis-(<50%)
      and necrosis-like (<30%) CA1 neurons. Colchicine did not provoke an anti
      apoptotic response in DGC at all. In addition, more than 70% of apoptosis- and
      necrosis-like CA1 neurons had completely lost their RCC subunits suggesting
      bioenergetic failure; by contrast, following colchicine injection, 88% of all
      apoptotic DGC presented RCC subunits. Thus, anti-apoptotic proteins may, in a
      subset of ischemic CA1 neurons, prevent cell death, while in others, affected by
      pronounced energy failure, they may cause secondary necrosis.

PMID- 17207632
TI  - Comorbidity in patients with cancer: prevalence and severity measured by
      cumulative illness rating scale.
AB  - Comorbidity is defined as the presence of one or more diseases in addition to an
      index disease. In elderly people, the number and severity of comorbidity increase
      with age. We report the comorbidity data of 536 patients treated as in-patients:
      231 elderly cancer patients (ECP), 172 younger cancer patients (YCP) and 133
      elderly patients admitted for non-cancer reasons (EMP). Comorbidity was assessed
      with the cumulative illness rating scale geriatric version (CIRS-G). Data on
      number of affected organ systems (levels 1-4), number of affected organ systems
      with severe disease (levels 3-4), and sum score of levels per patient are
      reported. The number of comorbidities increases with age. A 76% of ECP, 51% of
      YCP, and 79% of EMP have severe comorbidity. Palliative treatment approach is not
      associated with higher levels of comorbidity in ECP. Vascular disorders were the
      most common comorbidity. The difficulty to rate haematological comorbidity in
      cancer patients is reflected. This is the first report on detailed results of
      assessment of comorbidity measured by CIRS-G in cancer patients. In addition, we
      provide a comparison to an elderly group of patients admitted for non-cancer
      reasons.

PMID- 17207633
TI  - The in vivo contribution of hematopoietic cells to systemic TNF and IL-6
      production during endotoxemia.
AB  - Sepsis is a systemic inflammatory response syndrome resulting from an
      inappropriate innate immune response to infection. TNF and interleukin (IL)-6 are
      critically involved in this syndrome and although conclusive in vivo evidence is
      missing, innate immune cells are believed to be the principal producers of these
      cytokines. We investigated this assumption by performing bone marrow
      transplantations (BMT) between LPS-sensitive (C3H/HeN) and LPS-hyporesponsive
      (C3H/HeJ) mice. For adequate LPS-induced systemic TNF production, the
      hematopoietic cell population was absolutely required. In contrast, IL-6 could be
      detected in the circulation of LPS-treated chimeric mice, of which either the
      hematopoietic or the parenchymal cell population was hyporesponsive to LPS. So,
      whereas hematopoietic cells are the sole source of systemic TNF in an LPS-induced
      model of sepsis, both hematopoietic and parenchymal cells are required for
      systemic IL-6 production. Moreover, LPS-induced IL-6 production in parenchymal
      cells may be partially mediated by the TNF/TNF-R1 pathway as evidenced by the
      systemic IL-6 levels in LPS-treated wild type (WT), TNF-R1-deficient and chimeric
      mice.

PMID- 17207634
TI  - Effects of 17beta-estradiol and flutamide on splenic macrophages and splenocytes
      after trauma-hemorrhage.
AB  - Since splenic immune functions are depressed in metestrus females following
      trauma-hemorrhage, we hypothesized that administration of the androgen receptor
      antagonist flutamide at the onset of resuscitation will maintain the immune
      function of the spleen following trauma-hemorrhage. Female C57BL6/J mice
      (metestrus state, 8-12 weeks old), underwent laparotomy and hemorrhagic shock
      (35.0+/-5.0 mm Hg for 90 min) and received 17beta-estradiol (50 microg/25 g),
      flutamide (625 microg/25 g) or 17beta-estradiol+flutamide. Four hours after
      resuscitation, the in vitro productive capacity of different cytokines (TNF
      alpha, IL-6, IL-10, and IFN-gamma) by splenic MPhi and splenocytes were
      determined by flow cytometry. A significantly decreased cytokine production by
      both splenocytes and splenic MPhi was observed following trauma-hemorrhage
      compared to shams. Administration of 17beta-estradiol, flutamide and 17beta
      estradiol+flutamide following trauma-hemorrhage resulted in a significant
      increase in the in vitro IL-6 release by splenic MPhi. The TNF-alpha productive
      capacity, however, was only restored by 17beta-estradiol and 17beta
      estradiol+flutamide administration following trauma-hemorrhage. No significant
      effect of either treatment was observed with regard to the suppressed splenic
      MPhi IL-10 release. Anti-CD3 stimulation, administration of 17beta-estradiol and
      17beta-estradiol+flutamide, but not the administration of flutamide alone
      resulted in a significant increased release of TNF-alpha, IL-6 and IFN-gamma
      compared to vehicle-treated animals. No significant effect of either treatment
      was found on IL-10 productive capacity. These results collectively suggest that
      flutamide administration following trauma-hemorrhage in females has beneficial
      effects on splenic immune function. However, flutamide administration in
      combination with estrogen does not provide any significant, additional effects
      over 17beta-estradiol administration alone.

PMID- 17207635
TI  - The Ginkgo biloba extract EGb761 reduces stress sensitivity, ROS accumulation and
      expression of catalase and glutathione S-transferase 4 in Caenorhabditis elegans.
AB  - The standardised extract EGb761 from the leaves of Ginkgo biloba is a popular
      herbal dietary supplement and it is used as a phytopharmacon for the therapy of
      diverse cerebral insufficiencies. The beneficial impact of EGb761 is believed to
      be conferred by diverse biological actions under physiological conditions as well
      as in response to stress. In this study we examined effects of EGb761 in the
      model organism Caenorhabditis elegans. EGb761 reduced the body size but did not
      affect the reproduction of C. elegans. In fluorescence-based assays performed in
      microtiter plates we demonstrated the protective action of EGb761 by the increase
      of resistance to thermal stress and the attenuation of ROS accumulation under
      conditions of thermal stress in single living worms. Under normal conditions the
      lifespan of the worms was extended by the EGb761 supporting the beneficial
      effects found under stress conditions. In a reporter gene approach using
      individual living worms the expression of the stress-inducible glutathione S
      transferase 4 was shown to be reduced by EGb761 under physiological conditions as
      well as under oxidative stress. EGb761 also led to a decrease in transcription of
      the stress-inducible catalase genes. These results suggest that the beneficial
      impact of EGb791 on resistance to thermal stress and lifespan in C. elegans is at
      least partially due to its ability to relieve oxidative stress.

PMID- 17207636
TI  - Role of reactive oxygen species and spinal cord apoptotic genes in the
      development of neuropathic pain.
AB  - A mouse model of neuropathic pain consisting of chronic constriction injury (CCI)
      of the sciatic nerve was used to examine the involvement of reactive oxygen
      species (ROS) in early spinal cord pro-apoptotic gene over-expression during the
      development of neuropathic pain. RT-PCR analysis showed increased expression of
      bax, apoptotic protease-activating factor-1 (apaf-1), and caspase-9 in the dorsal
      horn spinal cord 3 days after chronic constriction injury of sciatic nerve.
      Consistent with biomolecular data, a marked increase in TUNEL-positive and
      caspase-3 active form was observed by 3 days CCI. Administration of phenyl-N-tert
      butylnitrone (PBN), a potent ROS scavenger, reduced the development of thermal
      hyperalgesia and mechanical allodynia at 1 and 3 days post-CCI, and decreased the
      mRNA levels of bax, apaf-1, and caspase-9. PBN also reduced apoptotic and active
      Caspase-3 positive profiles in the superficial laminae (I-III) of the spinal
      cord. This study provides evidence that PBN inhibits over-expression of pro
      apoptotic genes and neural apoptosis in the spinal cord dorsal horn induced by
      early-CCI of the sciatic nerve. These findings suggest that ROS regulate
      expression of some apoptotic genes which might play a role in the onset of
      neuropathic pain.

PMID- 17207637
TI  - Yeast apoptosis--from genes to pathways.
AB  - Yeast are eukaryotic unicellular organisms that are easy to cultivate and offer a
      wide spectrum of genetic and cytological tools for research. Yeasts Saccharomyces
      cerevisiae and Schizosaccharomyces pombe have successfully been used as models
      for human cell division cycle. Stress conditions, cellular ageing, failed mating,
      certain mutations or heterologous expression of proapoptotic genes induce yeast
      cell death with the characteristic markers of apoptosis. Several crucial
      regulators of apoptosis are conserved between metazoans and yeast. This simple
      model organism offers the possibility to identify conserved and new components of
      the apoptotic machinery and to elucidate the regulatory pathways beyond.

PMID- 17207638
TI  - Virtual spatial registration of stand-alone fNIRS data to MNI space.
AB  - The registration of functional brain data to common stereotaxic brain space
      facilitates data sharing and integration across different subjects, studies, and
      even imaging modalities. Thus, we previously described a method for the
      probabilistic registration of functional near-infrared spectroscopy (fNIRS) data
      onto Montreal Neurological Institute (MNI) coordinate space that can be used even
      when magnetic resonance images of the subjects are not available. This method,
      however, requires the careful measurement of scalp landmarks and fNIRS optode
      positions using a 3D-digitizer. Here we present a novel registration method,
      based on simulations in place of physical measurements for optode positioning.
      First, we constructed a holder deformation algorithm and examined its validity by
      comparing virtual and actual deformation of holders on spherical phantoms and
      real head surfaces. The discrepancies were negligible. Next, we registered
      virtual holders on synthetic heads and brains that represent size and shape
      variations among the population. The registered positions were normalized to MNI
      space. By repeating this process across synthetic heads and brains, we
      statistically estimated the most probable MNI coordinate values, and clarified
      errors, which were in the order of several millimeters across the scalp,
      associated with this estimation. In essence, the current method allowed the
      spatial registration of completely stand-alone fNIRS data onto MNI space without
      the use of supplementary measurements. This method will not only provide a
      practical solution to the spatial registration issues in fNIRS studies, but will
      also enhance cross-modal communications within the neuroimaging community.

PMID- 17207639
TI  - The worth of pictures: using high density event-related potentials to understand
      the memorial power of pictures and the dynamics of recognition memory.
AB  - To understand the neural correlates of the memorial power of pictures, pictures
      and words were systematically varied at study and test within subjects, and high
      density event-related potentials (ERPs) were recorded at retrieval. Using both
      conventional and novel methods, the results were presented as ERP waveforms, 50
      ms scalp topographies, and video clips, and analyzed using t-statistic
      topographic maps and nonparametric p-value maps. The authors found that a
      parietally-based ERP component was enhanced when pictures were presented at study
      or test, compared to when words were presented. An early frontally-based
      component was enhanced when words were presented at study compared to pictures.
      From these data the authors speculate that the memorial power of pictures is
      related to the ability of pictures to enhance recollection. Familiarity, by
      contrast, was enhanced when words were presented at study compared to pictures.
      From these results and the dynamic view of memory afforded by viewing the data as
      video clips, the authors propose an ERP model of recognition memory.

PMID- 17207640
TI  - 10/20, 10/10, and 10/5 systems revisited: their validity as relative head-surface
      based positioning systems.
AB  - With the advent of multi-channel EEG hardware systems and the concurrent
      development of topographic and tomographic signal source localization methods,
      the international 10/20 system, a standard system for electrode positioning with
      21 electrodes, was extended to higher density electrode settings such as 10/10
      and 10/5 systems, allowing more than 300 electrode positions. However, their
      effectiveness as relative head-surface-based positioning systems has not been
      examined. We previously developed a virtual 10/20 measurement algorithm that can
      analyze any structural MR head and brain image. Extending this method to the
      virtual 10/10 and 10/5 measurement algorithms, we analyzed the MR images of 17
      healthy subjects. The acquired scalp positions of the 10/10 and 10/5 systems were
      normalized to the Montreal Neurological Institute (MNI) stereotactic coordinates
      and their spatial variability was assessed. We described and examined the effects
      of spatial variability due to the selection of positioning systems and landmark
      placement strategies. As long as a detailed rule for a particular system was
      provided, it yielded precise landmark positions on the scalp. Moreover, we
      evaluated the effective spatial resolution of 329 scalp landmark positions of the
      10/5 system for multi-subject studies. As long as a detailed rule for landmark
      setting was provided, 241 scalp positions could be set effectively when there was
      no overlapping of two neighboring positions. Importantly, 10/10 positions could
      be well separated on a scalp without overlapping. This study presents a
      referential framework for establishing the effective spatial resolutions of
      10/20, 10/10, and 10/5 systems as relative head-surface-based positioning
      systems.

PMID- 17207641
TI  - Phylogenetic comparison of protein-coding versus ribosomal RNA-coding sequence
      data: a case study of the Lecanoromycetes (Ascomycota).
AB  - The resolving power and statistical support provided by two protein-coding (RPB1
      and RPB2) and three ribosomal RNA-coding (nucSSU, nucLSU, and mitSSU) genes
      individually and in various combinations were investigated based on maximum
      likelihood bootstrap analyses on lichen-forming fungi from the class
      Lecanoromycetes (Ascomycota). Our results indicate that the optimal loci (single
      and combined) to use for molecular systematics of lichen-forming Ascomycota are
      protein-coding genes (RPB1 and RPB2). RPB1 and RPB2 genes individually were
      phylogenetically more efficient than all two- and three-locus combinations of
      ribosomal loci. The 3rd codon position of each of these two loci provided the
      most characters in support of phylogenetic relationships within the
      Lecanoromycetes. Of the three ribosomal loci we used in this study, mitSSU
      contributed the most to phylogenetic analyses when combined with RPB1 and RPB2.
      Except for the mitSSU, ribosomal genes were the most difficult to recover because
      they often contain many introns, resulting in PCR bias toward numerous and
      intronless co-extracted contaminant fungi (mainly Dothideomycetes,
      Chaetothyriomycetes, and Sordariomycetes in the Ascomycota, and members of the
      Basidiomycota), which inhabit lichen thalli. Maximum likelihood analysis on the
      combined five-locus data set for 82 members of the Lecanoromycetes provided a
      well resolved and well supported tree compared to existing phylogenies. We
      confirmed the monophyly of three recognized subclasses in the Lecanoromycetes,
      the Acarosporomycetidae, Ostropomycetidae, and Lecanoromycetideae; the latter
      delimited as monophyletic for the first time, with the exclusion of the family
      Umbilicariaceae and Hypocenomyce scalaris. The genus Candelariella (formerly in
      the Candelariaceae, currently a member of the Lecanoraceae) represents the first
      evolutionary split within the Lecanoromycetes, before the divergence of the
      Acarosporomycetidae. This study provides a foundation necessary to guide the
      selection of loci for future multilocus phylogenetic studies on lichen-forming
      and allied ascomycetes.

PMID- 17207642
TI  - Non-invasive optical biosensor for assaying endogenous G protein-coupled
      receptors in adherent cells.
AB  - INTRODUCTION: Screening drugs against G protein-coupled receptors (GPCRs) - the
      single largest family of drug targets in the human genome - is still a major
      effort in pharmaceutical and biotech industries. Conventional cell-based assays
      generally measure a single cellular event, such as the generation of a second
      messenger or the relocation of a specific protein target. However, manipulation
      or engineering of cells is often a prerequisite for these technologies to achieve
      desired sensitivities. The present study is focused on the use of non-invasive
      and manipulation-free optical biosensors for assaying endogenous GPCRs in
      adherent cells. METHODS: Resonant waveguide grating (RWG) biosensor was applied
      to manifest ligand-induced dynamic mass redistribution (DMR) within the bottom
      portion of adherent cell layer. The DMR signatures mediated through the
      activation of several endogenous GPCRs in cells were characterized. Endogenous
      receptor panning was examined at cell system level by using a panel of agonists
      known to activate many GPCRs, and also at family receptor level by determining
      the efficacies of a set of family-specific agonists. RESULTS: Three major types
      of optical signatures were identified; each was correlated with the activation of
      a class of GPCRs, depending on the G protein with which the receptor is coupled
      (i.e., G(q), G(s) and G(i)). The characteristics of DMR signals, mostly the
      amplitude and kinetics of a DMR event, were dependent on the doses of agonists
      and the expression levels of endogenous receptors. All three classes of
      endogenous receptors were found in human epidermoid carcinoma A431 cells.
      Interestingly, the dose-dependent switching from one type of DMR signal to
      another was observed for several GPCR agonists examined. A small panel of P2Y
      receptor agonists exhibited distinct efficacies in three cell lines examined.
      DISCUSSIONS: The RWG biosensors were applicable to study the activation of
      endogenous GPCRs. Like second messengers or gene expression, the DMR signals
      obtained could be considered as novel and quantifiable physiological responses of
      living cells mediated through GPCRs and used for studying receptor biology.

PMID- 17207643
TI  - Osteoarthritis severity is sex dependent in a surgical mouse model.
AB  - OBJECTIVE: To investigate the role of sex hormones in cartilage degradation and
      progression of osteoarthritis (OA) in a murine model induced by destabilization
      of the medial meniscus (DMM). DESIGN: Accelerated OA development in mice was
      induced by transection of the menisco-tibial ligament, which anchors the medial
      meniscus to the tibial plateau. Intact male and female, and orchiectomized (ORX)
      male and ovariectomized (OVX) female mouse knee histology were compared for signs
      of OA following DMM. The effect of testosterone or estrogen addition in vivo was
      assessed in ORX males in the surgical OA model. RESULTS: OA severity was markedly
      higher in males than females after DMM. OVX females developed significantly more
      severe OA than control females. ORX males developed significantly less severe OA
      than control males. When ORX male mice were supplemented with exogenous
      dihydrotestosterone (DHT), the severity of OA was restored to the level
      experienced by the control male mice. Hip cartilage from mice of both sexes
      demonstrated similar spontaneous and interleukin-1alpha (IL-1alpha) induced
      proteoglycan (PG) release in vitro. DHT and 17-beta estradiol (E2) did not
      significantly alter the PG release pattern when supplemented to cartilage
      cultures of either sex. CONCLUSION: Sex hormones play a critical role in the
      progression of OA in the murine DMM surgical model, with males having more severe
      OA than females. Intact females had more OA than OVX females, indicating that
      ovarian hormones decrease the severity of OA in the female mice. Male hormones,
      such as testosterone, exacerbate OA in male mice as demonstrated by the fact that
      ORX mice experienced less OA than intact males, and that addition of DHT to ORX
      males was able to counteract the effect of castration and re-establish severe OA.

PMID- 17207644
TI  - Human parvovirus B19, varicella zoster virus, and human herpesvirus-6 in
      mesenchymal stem cells of patients with osteoarthritis: analysis with
      quantitative real-time polymerase chain reaction.
AB  - OBJECTIVE: To investigate whether there is a possible viral transmission using
      mesenchymal stem cells (MSCs) in autologous or allogeneic transplantation in the
      context of osteoarthritis (OA) patients. The presence of parvovirus B19 (B19),
      varicella zoster virus (VZV), and human herpesvirus-6 (HHV-6) was studied in MSCs
      from bone marrow of patients with OA and healthy controls. METHODS: MSCs were
      prepared from bone marrow aspirates obtained from 18 patients undergoing joint
      replacement as a result of OA and from 10 healthy controls. DNA was extracted
      from primary MSCs' culture established from these cells and quantitative real
      time polymerase chain reaction was performed to analyse the prevalence and viral
      load of B19, VZV and HHV-6. RESULTS: The prevalence of total viral DNA among
      patients with OA was 16.7% (3/18), with a mean viral load of 29.7 copies/microg
      of DNA. One out of 18 was positive for B19 (viral load, 61.2 copies/microg of
      DNA), two for VZV (mean viral load, 14.4 copies/microg of DNA), and none for HHV
      6. The prevalence of total viral DNA in the control group was 20% (2/10), with a
      mean viral load of 13.4 copies/microg of DNA. Both positive results were of B19
      parvoviruses. There were no statistically significant differences among patients
      and controls. CONCLUSIONS: This first approach to the viral prevalence in MSCs of
      bone marrow in OA patients and healthy controls seems to show a very low risk of
      viral transmission or reactivation in a possible MSCs' transplantation.

PMID- 17207645
TI  - Degenerative meniscus tears and mobility impairment in women with knee
      osteoarthritis.
AB  - OBJECTIVE: Meniscus tears are often presumed to be associated with a traumatic
      event, but they can also occur as a result of the cartilage degeneration process
      in osteoarthritis (OA). The aim of this paper is to describe the prevalence and
      clinical correlates of degenerative meniscus tears in women with knee OA. METHOD:
      The subjects were women screened for a double-blind, sham-exercise controlled
      clinical trial for women over 40 years of age with OA in at least one knee,
      according to American College of Rheumatology (ACR) clinical criteria. The
      presence of meniscus tears was assessed via a 3T Intera (Philips Medical Systems)
      magnetic resonance image (MRI). Clinical examination included a history of
      arthritis onset and physical examination of the lower extremities. Physical
      assessments included body composition, muscle strength, walking endurance, gait
      velocity, and balance. In addition, pain and disability secondary to OA, physical
      self-efficacy, depressive symptoms, habitual physical activity level and quality
      of life were assessed via questionnaires. RESULTS: Almost three-quarters (73%) of
      the 41 subjects had a medial, lateral, or bilateral meniscus tear by MRI. Walking
      endurance and balance performance were significantly impaired in subjects with a
      degenerative meniscus tear, compared to subjects without tears, despite similar
      OA duration, symptoms, and disability, body composition, and other clinical
      characteristics. CONCLUSION: Meniscus tears, diagnosed by MRI, are very common in
      older women with knee OA, particularly in the medial compartment. These
      incidentally discovered tears are associated with clinically relevant impairments
      of balance and walking endurance relative to subjects without meniscus tears. The
      explanation for this association requires further study.

PMID- 17207646
TI  - Cytogenetic analysis of human bone marrow-derived mesenchymal stem cells passaged
      in vitro.
AB  - This study concerns the cytogenetic stability of in vitro human bone marrow
      derived mesenchymal stem cells (MSCs) in primary culture and after passaging.
      Bone marrow samples were collected from seven brain malfunction patients involved
      in autologous MSC transplantation trials. Chromosome preparations from primary
      MSC cultures and after 3 passages were analyzed by conventional staining and G
      banding techniques. All MSCs showed normal diploid karyotypes, 46 XY or 46 XX,
      without aneuploidy or polyploidy; chromosome structural abnormalities were not
      detected. The results indicate that the in vitro cultured MSCs retained normal
      cytogenetics before being transplanted back into the patients.

PMID- 17207647
TI  - A quantitative colorimetric method of measuring alkaline phosphatase activity in
      eukaryotic cell membranes.
AB  - Alkaline phosphatase (ALP) is glycoprotein structured metalophosphatase with
      several defined functions. It is present in many tissues of all living beings
      from bacteria to mammals. The enzyme may catalyse the hydrolysis of various
      monophosphate esters at alkaline pH. The objective of this study was to quantify
      ALP functioning particularly in the membranes of eukaryotic cells. The membranes
      of seven different cells (myeloma cells; hybrid cells; erythroleukaemia cells;
      lymphocytes and erythrocytes) were tested for ALP activity using a cellular
      enzyme assay, which is based on the conversion of para-nitrophenylphosphate (p
      NPP) to para-nitrophenol and the colorimetric determination of the resulting
      coloured product. The test system was optimised with respect to substrate
      concentration, reaction time and the number of cells used as a source of enzyme.
      The obtained values were converted to quantitative results through a standard
      curve created using commercial ALP. In order to determine the effect of serum
      concentration on enzyme activity, 1G2 hybridoma, which is among the cells used in
      this study and which synthesizes monoclonal antibody against human serum albumin,
      was produced in different serum concentrations ranging from 0 to 15%.

PMID- 17207648
TI  - Results of endografting of the aortic arch in different landing zones.
AB  - INTRODUCTION: Endovascular approach to the aortic arch is an appealing solution
      for selected patients. Aim of this study is to compare the technical and clinical
      success recorded in the different anatomical settings of endografting for aortic
      arch disease. METHODS: Between June 1999 and October 2006, among 178 patients
      treated at our Institution for thoracic aorta disease with a stent-graft, the
      aortic arch was involved in 64 cases. According to the classification proposed by
      Ishimaru, aortic "zone 0" was involved in 14 cases, "zone 1" in 12 cases and
      "zone 2" in 38 cases. A hybrid surgical procedure of supraortic debranching and
      revascularization was performed in 37 cases to obtain an adequate proximal aortic
      landing zone. RESULTS: "Zone 0" (14 cases). Proximal neck length: 44+/-6mm.
      Initial clinical success 78.6%: 2 deaths (stroke), 1 type Ia endoleak. At a mean
      follow-up of 16.4+/-11 months the midterm clinical success was 85.7%. "Zone 1"
      (12 cases). Proximal neck length: 28+/-5mm. Initial clinical success 66.7%: 0
      deaths, 4 type Ia endoleaks. At a mean follow-up of 16.9+/-17.2 months the
      midterm clinical success was 75.0%. "Zone 2" (38 cases) Proximal neck length:
      30+/-5mm. Initial clinical success 84.2%: 2 deaths (1 cardiac arrest, 1
      multiorgan embolization), 3 type Ia endoleaks, 1 case of open conversion. Two
      cases of delayed transitory paraparesis/paraplegia were observed. At a mean
      follow-up of 28.0+/-17.2 months the midterm clinical success was 89.5%.
      CONCLUSIONS: Total debranching of the arch for "zone 0" aneurysms allowed to
      obtain a longer proximal aortic landing zone with lower incidence of endoleak,
      however a higher risk of cerebrovascular accident was observed. The relatively
      high incidence of adverse events in "zone 1" could be associated to a shorter
      proximal neck, therefore this landing zone is reserved for patients unfit for
      sternotomy. In case of endoleak, discovered after a satisfactorily positioned
      endograft in the arch, the rate of spontaneous resolution within the first 6
      months is high.

PMID- 17207649
TI  - Non-ketotic hyperglycinemia is usually not detectable by tandem mass spectrometry
      newborn screening.
AB  - Diagnosis of Non-Ketotic Hyperglycinemia by MSMS newborn screening might benefit
      patients with post-neonatal presentation. We screened 733,527 babies over eight
      years, and nine babies were subsequently diagnosed with NKHG. Two had newborn
      glycine levels above our cut-off and presented within 72 h. The remaining
      patients could not have been diagnosed by newborn screening without an
      unacceptably high recall rate. We conclude that babies with NKHG are not usually
      identifiable by current newborn screening strategies.

PMID- 17207650
TI  - Cavitation--a novel technique for making stable nano-suspensions.
AB  - The purpose of the present study was to obtain nano-scale particles of styrene
      butadiene rubber. As SBR particles are elastic in nature, conventional methods of
      size reductions such as impacting, grinding are unable to achieve the final size.
      So, attempts have been made here to make the nano-particles of the SBR using
      cavitation technique. Both acoustic and hydrodynamic cavitation techniques have
      been employed and studied. Hydrodynamic cavitation has been proved to be more
      energy efficient than the acoustic cavitation on the basis of various parameters.
      The maximum production rate equivalent to 2 kg/h (solid processing) has been
      achieved in the newly developed hydrodynamic cavitation set-up (made in house).
      Similar to transient cavitation, stable cavitation has also been shown to
      contribute for reduction in the size of the material with very low variation in
      size. This technique has been proved successful for the size-reduction of the
      elastic material to nano-scale, thus it may also be used for the size-reduction
      of the other brittle and hard material by adjusting various cavitational
      parameters.

PMID- 17207651
TI  - Impact of ultrasound on hydrophobic interactions in solutions: ultrasonic
      retardation of benzoin condensation.
AB  - Kinetics of the benzoin condensation of benzaldehyde in presence of KCN as the
      catalyst in water and in ethanol-water binary solutions were investigated without
      sonication and under ultrasound at 22 kHz. A statistically significant 20%
      decrease of the rate was observed in water. The retardation effect of ultrasound
      gradually decreases up to 45 wt% ethanol content. We report an evidence of
      ultrasonic retardation of reactions and thereby a direct evidence for
      sonochemical processes in the bulk solution. Ultrasound can disturb solvation of
      the species in the solution. If breaking down the stabilization of the encounter
      complexes between the reagents, sonication hinders the reaction while
      perturbation of the solvent-stabilization of the reagents accelerates the
      reaction.

PMID- 17207652
TI  - Sonochemistry and the environment - providing a "green" link between chemistry,
      physics and engineering.
AB  - Environmental protection and green science have an integral association and yet
      both terms can mean different things to different people and both refer to
      methods of preventing or removing pollution. The former includes such things as
      the development of low pollution fuels (including the use of biodiesel and fuel
      cells for vehicles) and the search for cleaner synthetic routes in the chemical
      industry. The latter tends to be more closely associated with the clean-up of the
      environment e.g. the purification of water (chemical and biological), the
      decontamination of the atmosphere and soil. In this article recent developments
      in the application of ultrasound in both environmental protection and remediation
      will be considered.

PMID- 17207653
TI  - Phonological typicality and sentence processing.
AB  - In studies of language, it is widely accepted that the form of a word is
      independent of its meaning and syntactic category. Thus, the relationship between
      phonological form and grammatical class would not be expected to affect reading
      time. However, Farmer et al. have now shown that the phonological typicality of a
      noun or verb influences how rapidly it is read. This finding has implications for
      both sentence processing and the interpretation of fixation patterns in reading.

PMID- 17207654
TI  - Modern treatment options for the therapy of keratoconus.
AB  - The following case report describes the implantation of intrastromal corneal ring
      segments (ICRS) and the postoperative contact lens treatment in a 42-year-old
      patient with bilateral advanced keratoconus. The patient had a preoperative
      contact lens intolerance. After femtosecond laser assisted surgery and the
      implantation of ICRS new custom mini-scleral contact lenses were fitted. The
      postoperative subjective and objective contact lens tolerance was excellent.

PMID- 17207655
TI  - Continuous intraarterial infusion chemotherapy for early lip cancer.
AB  - Most lip cancers are usually diagnosed and can be treated with good prognosis at
      an early stage. This study reports our experience of treating seven, previously
      untreated, patients with lip cancer in stage I or II using intraarterial infusion
      chemotherapy with a single agent. They were all males with ages ranging from 37
      to 69 years. An implantable port-catheter system was used for catheterization.
      Methotrexate 50mg was infused continuously to the external carotid artery every
      24h using a portable pump. Methotrexate was given continuously for a mean period
      of 7 days (range, 4-10 days) and the total administrated dose of methotrexate for
      intraarterial infusion ranged from 200 to 500 mg (mean, 350 mg). These seven
      patients were then given weekly bolus of methotrexate (25mg) via intraarterial
      route for a range of 6-12 weeks. In every case the tumor regressed dramatically
      and disappeared completely after treatment within a mean period of 2.5 months.
      Only one patient died, of non-disease related pneumonia 3 years after infusion
      therapy. The remaining patients are still alive and no recurrence of carcinoma
      has been observed at a median follow-up period of 28 months. There was no
      catheter-related complication. The side effects of infusion chemotherapy were
      mild and tolerable. Our technique of continuous intraarterial infusion therapy
      for treatment of early lip cancers seems to be as effective as other standard
      techniques such as surgery or radiation therapy. This modality achieves good
      tumor response rates, an excellent cosmetic result, preservation of function and
      minimal side effects.

PMID- 17207656
TI  - Utility of 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography and
      positron emission tomography/computed tomography imaging in the preoperative
      staging of head and neck squamous cell carcinoma.
AB  - The combination of 18F-fluorodeoxyglucose (FDG) positron emission tomography
      (PET) and computed tomography (CT) has been reported to be more accurate than CT
      or PET alone in a preoperative setting. We compared the diagnostic utility of
      preoperative PET/CT, PET and CT/MRI in 167 patients with newly diagnosed head and
      neck squamous cell carcinoma (HNSCC), of whom 104 underwent FDG PET and 63
      underwent combined PET/CT with all receiving CT/MRI. These preoperative PET,
      PET/CT, and CT/MRI results were reviewed and their accuracies were compared in
      patients in whom diagnosis was confirmed histopathologically. Age, sex, primary
      sites and stage, and nodal involvement were comparable between two groups. The
      accuracy of PET and PET/CT for detecting primary tumors and cervical metastases
      was comparable, but significantly higher than that of CT/MRI (98%-97% vs. 86-88%
      for primary; 92%-93% vs. 85%-86% for neck on a level-by-level basis; P<.05). PET
      and PET/CT gave false negative results: in 2 (2%) and 2 (3%) patients for primary
      tumors; in 6 (6%) and 3 (5%) patients for neck metastases, respectively. PET and
      PET/CT also gave false-positive results for cervical metastases in 5 (5%) and 4
      (6%) patients, respectively. Compared with PET alone, preoperative FDG PET/CT may
      not yield significantly improved diagnostic accuracy in patients with HNSCC.
      Moreover, despite their high accuracy, PET and PET/CT may not abrogate the need
      for conventional imaging and pathologic staging based on primary resection and
      neck dissection.

PMID- 17207657
TI  - Overexpression of GLUT-1 is associated with resistance to radiotherapy and
      adverse prognosis in squamous cell carcinoma of the oral cavity.
AB  - This study tested the hypothesis that GLUT-1 is a marker of radioresistance in
      oral squamous cell carcinomas (OSCC). A GLUT-1 labeling index (LI) was determined
      by immunohistochemistry in 40 pretreatment OSCC biopsies. Radiation responses
      were categorized by histopathology of the resection specimens. Associations
      between the LI and radiation response, Kaplan-Meier survival estimates and Cox
      regression analysis for the variables GLUT-1, T-stage, N-stage and chemotherapy
      were examined. The median LI was 64.2% (range 14-100%). Tumors with >65% of GLUT
      1+cells were more resistant to radiation (p=0.023). Overall survival was higher
      (p=0.044) for subjects with low LI (<median value) than those with high LI
      (>median value). The Cox regression analysis confirmed the prognostic
      significance of GLUT-1. Our results indicate that pre-treatment GLUT-1 expression
      in the tumor is a marker of radioresistance in OSCC, with high expression being
      associated with poor radiation response and shorter survival.

PMID- 17207658
TI  - Analysis of the base excision repair genes MTH1, OGG1 and MUTYH in patients with
      squamous oral carcinomas.
AB  - A number of environmental factors, such as tobacco and alcohol, have been
      implicated, through oxidative DNA damage, in the development of squamous cell
      carcinomas of the head and neck (SCCHN). Several pathways are involved in the
      repair of DNA lesions caused by oxidative stress, such as the base excision
      repair system (BER), which repairs mutation involving 8-oxoguanine and comprises
      the MUTYH, OGG1 and MTH1 genes. We analysed 29 patients, assessing germline
      polymorphisms or mutations in these genes by complete genomic sequencing of exons
      and adjacent intronic regions. Thirty healthy blood donors served as controls. No
      pathogenic germline mutations were identified. We found common and rare new
      variants in the coding and adjacent intronic regions. In summary, our data do not
      support a major role for MUTYH, OGG1 and MTH1 variants in the etiology of
      sporadic squamous oral/oropharyngeal carcinomas. This does not exclude the
      involvement of the three BER genes in the tumorigenesis of SCCHN through other
      mechanisms such as promotor hypermethylation, genomic rearrangements or mutations
      involving regulatory sequences.

PMID- 17207659
TI  - Clinicopathologic significance of EpCAM expression in squamous cell carcinoma of
      the tongue and its possibility as a potential target for tongue cancer gene
      therapy.
AB  - Epithelial adhesion molecule (EpCAM) is a transmembrane glycoprotein involved in
      intercellular adhesion. In particular, EpCAM appears to be overexpressed by the
      majority of human epithelial carcinomas, including colorectal, breast, head and
      neck, and hepatic carcinomas. We therefore hypothesized that EpCAM would be a
      good molecular target for cancer gene therapy. EpCAM protein expression in 48
      primary tongue cancers and 10 normal oral mucosa was evaluated using anti-EpCAM
      immunohistochemistry, and correlation was examined with the clinicopathologic
      factors. In four human tongue cancer cell lines (SAS, HSC-2, OSC19 and OSC20), we
      investigated EpCAM expression by reverse transcription-polymerase chain reaction
      (RT-PCR). The invasive potential of cancer cells was evaluated using Matrigel
      invasion assay. Moreover, the effect of EpCAM inhibition was analyzed using RNA
      interference (RNAi). EpCAM overexpression was detected in 30 of 48 tongue cancers
      (62.5%), and was significantly higher in primary squamous cell carcinoma (SCC) of
      the tongue than in normal oral mucosa. The expression of EpCAM was significantly
      associated with tumor size, regional lymph node metastasis, histological
      differentiation and invasion pattern. Cancer cell lines with higher EpCAM
      expression had more invasive potential. Moreover, RNAi-mediated EpCAM reduction
      decreased the invasion potential and proliferation activity. These results
      indicated that the overexpression of EpCAM was correlated with a more aggressive
      phenotype of tongue cancer. Moreover, we suggested that EpCAM could be a
      molecular target, and that RNAi targeting EpCAM could be useful for tongue cancer
      gene therapy.

PMID- 17207660
TI  - Diruthenium, diiron and mixed ruthenium-iron tetraiminediphenolate macrocyclic
      complexes: synthetic route, spectroscopy, molecular mechanics and redox
      properties.
AB  - A series of diruthenium(II), [Ru(2)(tidf)Cl(2)(H(2)O)(2)] x H(2)O, diiron(II)
      [Fe(2)(tidf)(MeOH)(4)](ClO(4))(2) and mixed ruthenium(II)-iron(II)
      [Ru(MeOH)(2)FeCl(H(2)O)(tidf)](ClO(4)) (tidf=a two compartment
      tetraiminediphenolate macrocycle) complexes were prepared and characterized by
      elemental analysis, FTIR, UV-vis, cyclic voltammetry and semi-empirical molecular
      mechanics calculations.

PMID- 17207661
TI  - SIR2: a potential target for calorie restriction mimetics.
AB  - Calorie restriction (CR) extends lifespan in a wide variety of species and
      mitigates diseases of aging in mammals. Here, we describe the evidence that the
      silent information regulator 2 (SIR2) gene, which encodes a nicotinamide adenine
      dinucleotide (NAD)-dependent deacetylase, regulates lifespan and mediates CR in
      lower species such as Saccharomyces cerevisiae and Caenorhabditis elegans. We
      discuss the emerging roles of mammalian SIR2 homologs in regulating physiological
      changes triggered by CR and their potential connections to diseases of aging. We
      conclude with the recent advances on small molecules that activate the enzymatic
      activity of SIR2 as potential CR mimetics. The SIR2 family represents an
      evolutionarily conserved lifespan regulator. Modulating the activity of SIR2
      might provide effective CR mimetics to combat diseases of aging.

PMID- 17207662
TI  - The tripartite synapse: roles for gliotransmission in health and disease.
AB  - In addition to being essential supporters of neuronal function, astrocytes are
      now recognized as active elements in the brain. Astrocytes sense and integrate
      synaptic activity and, depending on intracellular Ca(2+) levels, release
      gliotransmitters (e.g. glutamate, d-serine and ATP) that have feedback actions on
      neurons. Recent experimental results have raised the possibility that
      quantitative variations in gliotransmission might contribute to disorders of the
      nervous system. Here, we discuss targeted molecular genetic approaches that have
      demonstrated that alterations in protein expression in astrocytes can lead to
      serious changes in neuronal function. We also introduce the concept of 'astrocyte
      activation spectrum' in which enhanced and reduced gliotransmission might
      contribute to epilepsy and schizophrenia, respectively. The results of future
      experimental tests of the astrocyte activation spectrum, which relates
      gliotransmission to neurological and psychiatric disorders, might point to a new
      therapeutic target in the brain.

PMID- 17207663
TI  - Sand flies and Leishmania: specific versus permissive vectors.

PMID- 17207664
TI  - Psychological morbidity and female urinary incontinence.
AB  - Female urinary incontinence is a common yet distressing condition. It affects
      women of all ages, but is especially common in the elderly. Its prevalence ranges
      from 15 to 55%, depending on age and population studied. Despite the ubiquity of
      female urinary incontinence, many incontinent women do not voice their suffering,
      and urinary incontinence has therefore been dubbed 'the silent epidemic'. The
      physical impact and social isolation associated with urinary incontinence lead to
      impairment of quality of life and psychological well-being. It is the aim of this
      review to discuss the epidemiology and psychological impact of urinary
      incontinence. The recognition and management of incontinence-related
      psychological morbidity are also explored.

PMID- 17207666
TI  - Graded expression of Zfp462 in the embryonic mouse cerebral cortex.
AB  - We describe the isolation and embryonic pattern of expression of mouse Zfp462, a
      novel zinc finger protein gene. Zfp462 was isolated in a microarray-based search
      to identify genes differentially expressed in the late embryonic mouse cerebral
      cortex. The mouse Zfp462 deduced amino acid sequence is 2500 residues in length
      and contains 23 C(2)H(2)-type zinc finger motifs. Zfp462 shares low homology
      (30%) with non-vertebrate zinc finger proteins, suggesting that it is vertebrate
      specific. However, domains found only in vertebrate-specific zinc finger
      proteins, such as the KRAB and SCAN domains, were not identified in Zfp462. We
      show that Zfp462 is expressed in the developing central nervous system, branchial
      arches, otic vesicles, sensory ganglia, somites and limbs. In the central nervous
      system, Zfp462 is expressed at the headfold stage and is later expressed in the
      developing forebrain, brainstem and spinal cord. Interestingly, beginning at
      E13.5, Zfp462 is expressed in a graded pattern in the mouse cerebral cortex. As
      predicted by the microarray analysis, Zfp462 is expressed at its highest levels
      in the caudal and medial cerebral cortex. Its expression in cortical layers is
      greatest in the marginal zone, the cortical plate and the subventricular zone.
      Zfp462 thus belongs to a growing family of molecular determinants that are
      expressed in a graded pattern in the developing cerebral cortex. This family
      includes transcription factor-encoding genes such as COUP-TF1, Emx2 and Pax6,
      which have been implicated in the process of cortical arealization.

PMID- 17207665
TI  - Evidence supporting changes in Nogo-B levels as a marker of neointimal expansion
      but not adaptive arterial remodeling.
AB  - Both neointimal hyperplasia and inward remodeling contribute to restenosis and
      lumen loss. Nogo-B has been recently described as an inhibitor of vascular injury
      and neointimal hyperplasia. To determine whether Nogo-B expression may be a
      mediator of inward remodeling, we examine the localization of expression of Nogo
      B in an in vivo model that examines both neointimal hyperplasia and inward
      remodeling. The rabbit carotid artery was subjected to balloon injury, outflow
      branch ligation to reduce flow, or both balloon injury and reduction in flow. In
      balloon injury-induced neointimal hyperplasia Nogo-B expression was reduced in
      the intima and media but stimulated in the adventitia. In low flow-induced inward
      remodeling medial Nogo-B expression was not reduced and adventitial Nogo-B
      expression was not stimulated. Low flow significantly augmented balloon injury
      induced neointimal hyperplasia and was accompanied by reduced intimal and medial
      Nogo-B expression, and increased adventitial Nogo-B expression in both smooth
      muscle cells and macrophages. Low flow-induced inward remodeling is not
      associated with changes in medial Nogo-B expression and is distinct from injury
      induced neointimal hyperplasia. Pharmacological strategies to inhibit neointimal
      hyperplasia and restenosis using normal flow models may only partially account
      for lumen loss and therefore may not accurately predict responses in patients
      with extensive outflow disease.

PMID- 17207667
TI  - Formation of high-molecular-weight protein adducts by methyl docosahexaenoate
      peroxidation products.
AB  - In the present study, the formation of modified proteins by methyl
      docosahexaenoate (DHA) peroxidation products in the presence of a metal-catalyzed
      oxidation system was investigated. Metal-catalyzed oxidation of mixtures
      containing bovine serum albumin (BSA) and DHA led to formation of two high
      molecular weight derivatives of BSA. One had a mass of 71.5 kDa as determined by
      two-dimensional electrophoresis, matrix assisted laser desorption and ionization
      mass spectrometer (MALDI MS) analysis. The other was estimated to be 93 kDa by
      SDS-PAGE electrophoresis. The exposure of BSA to DHA also led to the generation
      of carbonyl groups. Oxygen radical scavengers could inhibit these modifications
      induced by DHA peroxidation. Furthermore, there was little difference of the
      peptides mass fingerprinting between the two kinds of modified high-molecular
      weight proteins. These results suggest that oxygen radicals formed during lipid
      peroxidation are involved in the formation of protein derivatives. Our study may
      be important in the understanding the specific role of docosahexaenoic acid in
      the formation of modified proteins during aging and its related diseases.

PMID- 17207668
TI  - Functional outcomes of intramuscular botulinum toxin type a and occupational
      therapy in the upper limbs of children with cerebral palsy: a randomized
      controlled trial.
AB  - OBJECTIVE: To investigate the functional outcomes of botulinum toxin type A (BTX
      A) injections to the upper limb in combination with occupational therapy (OT) in
      children with cerebral palsy (CP). DESIGN: Randomized controlled trial with
      follow-up at 2 weeks, 3 months, and 6 months. SETTING: Specialist outpatient
      physical disabilities clinic within a public pediatric teaching hospital.
      PARTICIPANTS: Eighty children with spastic quadriplegic, triplegic, or hemiplegic
      CP from these clinics were randomly assigned to BTX-A plus OT, BTX-A alone, OT
      alone, or a no-treatment control group. INTERVENTIONS: Single set of BTX-A
      (Botox) injections and 12 weeks of OT. MAIN OUTCOME MEASURES: Canadian
      Occupational Performance Measure (COPM) and Goal Attainment Scale (GAS). RESULTS:
      The combination of BTX-A and OT resulted in accelerated attainment of functional
      goals measured by the COPM and GAS. There were no differences between groups on
      the Melbourne Assessment of Unilateral Upper Limb Function, Quality of Upper
      Extremity Skills Test, Pediatric Evaluation of Disability Inventory, Child Health
      Questionnaire, or active and passive range of motion. As expected, there was a
      significant reduction in muscle tone at follow-up 2 weeks after injection, which
      returned to baseline level by 6 months. CONCLUSIONS: OT enhanced individualized
      functional outcomes following BTX-A injections in the upper limbs of children
      with CP.

PMID- 17207669
TI  - Functional outcomes from inpatient rehabilitation after traumatic brain injury:
      how do Hispanics fare?
AB  - OBJECTIVE: To examine the relation between Hispanic ethnicity and rehabilitation
      outcome in traumatic brain injury (TBI) survivors. DESIGN: Retrospective study.
      SETTING: Longitudinal dataset of the Traumatic Brain Injury Model Systems
      national database. PARTICIPANTS: Persons (N=3056; 2745 whites vs 311 Hispanics)
      with moderate to severe TBI hospitalized between 1989 and 2003. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: Functional outcomes at discharge and 1
      year follow-up (Disability Rating Scale [DRS], FIM instrument). Glasgow Outcome
      Scale-Extended (GOS-E), and the Community Integration Questionnaire (CIQ) were
      measured at follow-up only. RESULTS: At admission, Hispanics were less educated
      (P</=.001), earned less money (P</=.05), and were younger (P</=.001) than whites.
      Hispanics had lower GOS-E scores (P</=.01) at acute hospital admission compared
      with whites. Despite similar functional status at inpatient rehabilitation
      discharge, Hispanic ethnicity was associated with poorer functional outcomes at 1
      year postinjury (DRS, FIM, CIQ), after controlling for age, length of
      posttraumatic amnesia, injury severity, DRS score at admission, FIM score at
      admission, and preinjury educational level (P<.05). CONCLUSIONS: Hispanics showed
      significantly reduced long-term functional outcome after rehabilitation relative
      to whites. Rehabilitation professionals should recognize the possible impact of
      individual differences and diverse sociodemographic, injury, and rehabilitation
      characteristics so that differential health outcomes among TBI survivors can be
      reduced or eliminated.

PMID- 17207670
TI  - The relationship between electrodiagnostic findings and patient symptoms and
      function in carpal tunnel syndrome.
AB  - OBJECTIVE: To examine whether, in patients with carpal tunnel syndrome (CTS),
      electrodiagnostic study findings were associated with patient symptom severity
      and functional limitations after controlling for potentially confounding
      variables including depression, somatization, and pain-related catastrophizing.
      DESIGN: Cross-sectional design including data from 2 ongoing CTS studies.
      SETTING: Patients enrolled from hospitals and clinics in Washington State between
      October 2002 and February 2006. PARTICIPANTS: Adults with CTS (N=215) (based on
      symptoms and abnormal electrodiagnostic findings) were analyzed. Exclusion
      criteria were any mass, tumor, severe trauma, or deformity in the hand or wrist,
      radiculopathy, polyneuropathy, pregnancy, lactation, or severe CTS.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The Carpal Tunnel Syndrome
      Assessment Questionnaire (CTSAQ) functional status scale assessed the ability to
      perform 9 common hand-related tasks. The CTSAQ symptom severity scale included 11
      items that assess pain, numbness, and weakness. Patients also rated their average
      hand and wrist pain in the last month. RESULTS: With and without controlling for
      patient characteristics, including age, sex, body mass index, symptom duration,
      depression, somatization, and pain-related catastrophizing, there were no
      statistically significant relationships between the electrodiagnostic findings
      and patient functional status and symptom severity. CONCLUSIONS:
      Electrodiagnostic findings and patient CTS-related symptoms and function appear
      to be independent measures. Clinicians and researchers interested in CTS outcomes
      need to assess both.

PMID- 17207671
TI  - Effectiveness of loaded sit-to-stand resistance exercise for children with mild
      spastic diplegia: a randomized clinical trial.
AB  - OBJECTIVE: To investigate effectiveness of a functional strengthening program,
      the loaded sit-to-stand (STS) resistance exercise, for children with cerebral
      palsy (CP). DESIGN: A single-blind, randomized block design. SETTING: STS
      exercises were carried out at the children's homes. PARTICIPANTS: Twenty children
      (12 boys, 8 girls; age range, 5-12y) with spastic diplegia CP and classified by
      the Gross Motor Function Classification System as level I or II were stratified
      by their severity and age and randomly allocated into either the experimental or
      control group. INTERVENTION: Both groups received their regular physical therapy.
      The experimental group underwent loaded STS exercise 3 times a week for 6 weeks.
      MAIN OUTCOME MEASURES: Goal dimension scores of the Gross Motor Function Measure
      (GMFM), gait speed, 1 repetition maximum (1-RM) of the loaded STS, isometric
      strength of knee extensor, and Physiological Cost Index (PCI). The outcome
      measures were conducted at the beginning and end of the 6-week study. RESULTS:
      After loaded STS exercise, the experimental group showed statistically
      significant differences in GMFM goal dimension scores, 1-RM STS, and PCI from the
      control group. The changes in gait speed and isometric strength of the knee
      extensor did not differ significantly between the 2 groups. CONCLUSIONS: After
      the loaded STS exercise, children with mild spastic diplegia improved their basic
      motor abilities, functional muscle strength, and walking efficiency.

PMID- 17207672
TI  - Measuring muscle strength for people with chronic obstructive pulmonary disease:
      retest reliability of hand-held dynamometry.
AB  - OBJECTIVE: To evaluate the retest reliability and quantify the degree of
      measurement error when measuring isometric muscle strength with a hand-held
      dynamometer for people with chronic obstructive pulmonary disease (COPD). DESIGN:
      Retest reliability of hand-held dynamometry for 4 muscle groups was assessed on 2
      occasions separated by a 2-week interval. SETTING: Community rehabilitation
      center. PARTICIPANTS: Eight men and 4 women (mean age +/- standard deviation,
      71.4+/-10.3y) with moderately severe COPD (percentage of predicted forced
      expiratory volume in 1 second, 41.5%+/-17.7%). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Muscle strength (in kilograms). Statistical analysis was
      conducted by calculating intraclass correlation coefficients and 95% confidence
      intervals for both group and individual scores. RESULTS: All reliability
      coefficients were greater than .79. Muscle strength would need to increase by
      between 4% and 18% in groups of people with COPD and between 34% and 58% in a
      person with COPD to be 95% confident of detecting real changes. CONCLUSIONS: Hand
      held dynamometry is suitable for monitoring change in muscle strength and testing
      hypotheses for groups of people with COPD. However, hand-held dynamometry is not
      likely to detect changes in muscle strength for a person with COPD.

PMID- 17207673
TI  - Influence of lever arm and stabilization on measures of hip abduction and
      adduction torque obtained by hand-held dynamometry.
AB  - OBJECTIVE: To examine the reliability of clinical techniques for testing hip
      abductor and adductor muscle performance. DESIGN: Repeated measures. SETTING:
      Academic laboratory. PARTICIPANTS: A sample of 21 healthy subjects (12 men, 9
      women) between 22 and 31 years of age. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURES: Reliability of repeated measures was estimated by calculating
      intraclass correlation coefficients. Torque production capability was calculated
      by multiplying force output obtained with a hand-held dynamometer by the length
      of the resistance lever arm. RESULTS: The reliability of abduction testing was
      greatest in the long-lever condition. Adduction test reliability was greatest in
      the long-lever condition with bench stabilization. The maximal hip abduction
      torque tested in the long-lever position was significantly greater (t(20)=9.21,
      P<.001) than that in the short-lever position. The maximal hip adduction torque
      occurred using a long lever for resistance application and a bench to stabilize
      the nontest leg (F(1,20)=15.64, P=.001). CONCLUSIONS: Muscle performance testing
      of hip abductors and adductors with a hand-held dynamometer can be performed with
      good to excellent intratester and intertester reliability. Hip abduction testing
      is best performed with a long lever. Hip adduction is best performed with a long
      lever and a bench to stabilize the nontest extremity.

PMID- 17207674
TI  - Relationship between step length asymmetry and walking performance in subjects
      with chronic hemiparesis.
AB  - OBJECTIVE: To understand the relationship between step length asymmetry and
      hemiparetic walking performance. DESIGN: Descriptive. SETTING: Gait analysis
      laboratory. PARTICIPANTS: Convenience sample of 49 subjects with chronic
      hemiparesis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subjects
      walked at their self-selected walking speed over both an instrumented mat and
      forceplates to collect spatiotemporal parameters and ground reaction forces,
      respectively. Step length asymmetry was quantified by using a step length ratio
      (SLR) defined as paretic step length divided by nonparetic step length. Paretic
      leg propulsion, self-selected walking speed, hemiparetic severity (assessed by
      Brunnstrom stages of motor recovery), and some spatiotemporal walking parameters
      quantified the hemiparetic walking performance. Paretic leg propulsion was
      quantified by the paretic propulsion (P(P)) ratio, calculated as the percentage
      contribution of paretic leg to the total propulsive impulse. RESULTS: Significant
      negative correlation (r=-.78) was revealed between SLR and P(P), indicating that
      subjects generating less propulsive force with the paretic leg walked
      asymmetrically with longer paretic steps than nonparetic steps. SLR and self
      selected walking speed revealed a weaker correlation (r=-.35), whereas
      hemiparetic severity correlated strongly with SLR (rho=-.53). CONCLUSIONS: Step
      length asymmetry is related to propulsive force generation during hemiparetic
      walking. Subjects generating least paretic propulsion walk with relatively longer
      paretic steps. This suggests that one of the mechanisms for the longer paretic
      step may be the relatively greater compensatory nonparetic leg propulsion.
      Further, those with more severe hemiparesis (those dependent on abnormal flexor
      and extensor synergies) walk with the longest paretic steps relative to
      nonparetic. Finally, our results indicated that asymmetrical step lengths may not
      necessarily limit the self-selected walking speed, likely due to other
      compensatory mechanisms.

PMID- 17207675
TI  - Walking while talking: effect of task prioritization in the elderly.
AB  - OBJECTIVE: To examine the effect of 2 instructions on the same walking while
      talking (WWT) task on task prioritization by nondisabled subjects. DESIGN: Cross
      sectional survey with within subject comparisons. SETTING: Community-based
      sample. PARTICIPANTS: Older adults (N=189; mean age, 80.2+/-4.9y), who did not
      meet criteria from the Diagnostic and Statistical Manual, Fourth Edition, for
      dementia and were able to independently perform activities of daily living.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Verbal and gait measures on
      the same WWT task with 2 different instructions: paying attention to both talking
      and walking (WWT-C) and paying attention only to talking (WWT-T). RESULTS: Task
      prioritization effects were seen on walking but not on talking. Compared with
      their baseline normal walking velocity (without talking), subjects slowed down
      more on WWT-T (median change, 28.3%) than WWT-C (median change, 26.4%). Comparing
      the 2 WWT conditions, velocity and cadence was slower during WWT-T compared with
      WWT-C, with longer stride length. Verbal output was not significantly different
      on the 2 conditions. CONCLUSIONS: Changing instructions while maintaining the
      same cognitive and motor tasks on WWT in older adults result in task
      prioritization effects.

PMID- 17207676
TI  - Quantification of lumbar stability by using 2 different abdominal activation
      strategies.
AB  - OBJECTIVE: To determine whether the abdominal hollowing technique is more
      effective for lumbar spine stabilization than a full abdominal muscle
      cocontraction. DESIGN: Within-subject, repeated-measures analysis of variance was
      used to examine the effect of combining each of 4 loading conditions with either
      the hollow or brace condition on the dependent variables of stability and
      compression. A simulation was also conducted to assess the outcome of a person
      activating just the transversus abdominis during the hollow. SETTING: Laboratory.
      PARTICIPANTS: Eight healthy men (age range, 20-33y). INTERVENTIONS:
      Electromyography and spine kinematics were recorded during an abdominal brace and
      a hollow while supporting either a bilateral or asymmetric weight in the hands.
      MAIN OUTCOME MEASURES: Spine stability index and lumbar compression were
      calculated. RESULTS: In the simulation "ideal case," the brace technique improved
      stability by 32%, with a 15% increase in lumbar compression. The transversus
      abdominis contributed .14% of stability to the brace pattern with a less than
      0.1% decrease in compression. CONCLUSIONS: Whatever the benefit underlying low
      load transversus abdominis activation training, it is unlikely to be mechanical.
      There seems to be no mechanical rationale for using an abdominal hollow, or the
      transversus abdominis, to enhance stability. Bracing creates patterns that better
      enhance stability.

PMID- 17207677
TI  - Perceived control is a concurrent predictor of activity limitations in patients
      with chronic idiopathic axonal polyneuropathy.
AB  - OBJECTIVES: To investigate (1) whether control perceptions (person's perception
      of ease or difficulty of performing behavior) and emotions contribute to activity
      limitations and if so (2) whether these variables mediate the relation between
      impairment and activity limitations in patients with chronic idiopathic axonal
      polyneuropathy (CIAP). DESIGN: Cross-sectional study. SETTING: Outpatient clinics
      of a university medical center. PARTICIPANTS: Fifty-six patients diagnosed with
      CIAP. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Control perceptions
      about performing activities (questionnaire based on the theory of planned
      behavior), emotions (Hospital Anxiety and Depression Scale), activity limitations
      (performance: Shuttle Walk Test [SWT]; self-report: Medical Outcomes Study 36
      Item Short-Form Health Survey [SF-36] physical functioning subscale, self
      reported ability to walk), and physical impairments (muscle strength, sensory
      function). RESULTS: Control perceptions significantly (P<.01) correlated with all
      measures of activity limitations (r range, .58-.69). Hierarchical multiple
      regression analyses showed that perceived control explained 9% of the variance in
      the SWT (beta=.34, P<.01), 12% in the SF-36 (beta=.40, P<.01), and 24% in ability
      to walk (beta=.54, P<.01). In all measures of activity limitations, perceived
      control significantly mediated the effect of impairment. CONCLUSIONS: Perceived
      control explained and mediated variance in activity limitations, whereas emotions
      did not. This suggests that increasing patients' perceptions of control might
      enhance performance of activities, even without changes in impairment.

PMID- 17207678
TI  - Effects of circuit resistance training on fitness attributes and upper-extremity
      pain in middle-aged men with paraplegia.
AB  - OBJECTIVE: To examine the effects of circuit resistance exercise (CRT) training
      on muscle strength, endurance, anaerobic power, and shoulder pain in middle-aged
      men with paraplegia. DESIGN: Repeated testing. SETTING: Academic medical center.
      PARTICIPANTS: Seven men (age range, 39-58y) with motor-complete paraplegia from
      T5 to T12 and confirmed shoulder pain occurring during daily activities.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subjects underwent a 4
      month CRT program using alternating resistance maneuvers and high-speed, low
      resistance arm exercise. One-repetition maximal force was measured before
      training and monthly thereafter. Pretraining and posttraining peak oxygen uptake
      (Vo(2)peak) was measured by graded arm testing. Anaerobic power was measured
      before and after training using a 30-second Wingate Anaerobic Test. Shoulder pain
      was self-evaluated by an index validated for people with spinal cord injury
      (Wheelchair Users Shoulder Pain Index [WUSPI]). RESULTS: Strength increases
      ranging from 38.6% to 59.7% were observed for all maneuvers (P range, .005-.008).
      Vo(2)peak increased after training by 10.4% (P=.01), and peak and average
      anaerobic power increased by 6% (P=.001) and 8.6% (P=.005), respectively. WUSPI
      scores +/- standard deviation were lowered from 31.9+/-24.8 to 5.7+/-5.9
      (P=.008), with 3 of 7 subjects reporting complete resolution of shoulder pain.
      CONCLUSIONS: CRT improves muscle strength, endurance, and anaerobic power of
      middle-aged men with paraplegia while significantly reducing their shoulder pain.

PMID- 17207679
TI  - Consequences of a cross slope on wheelchair handrim biomechanics.
AB  - OBJECTIVE: To test the hypothesis that pushing on a cross slope leads to
      increased handrim loading compared with that found on a level surface. DESIGN:
      Case series. SETTING: Biomechanics laboratory. PARTICIPANTS: Twenty-six manual
      wheelchair users. INTERVENTION: Subjects pushed their own wheelchairs on a
      research treadmill set to level, 3 degrees , and 6 degrees cross slopes.
      Propulsion speed was self-selected for each cross-slope condition. Handrim
      biomechanics were measured for the downhill wheel, using an instrumented
      wheelchair wheel and a motion capture system. MAIN OUTCOME MEASURES: Speed, peak
      kinetics (force, rate of loading, torque), push angle, cadence, push distance,
      and power output were averaged over a 20-push set for each subject and each cross
      slope condition. Outcomes were compared across cross slopes using a repeated
      measures analysis of variance. RESULTS: Push angle and cadence were unaffected by
      cross slope. A trend of decreasing self-selected speeds with increasing cross
      slope was not significant. There were considerable increases in the peak kinetic
      measures, with the axial moment increasing by a factor of 1.8 on the 6 degrees
      cross slope (P=.000). More pushes were required to cover the same distance when
      on a cross slope (P<.034). The power required for propulsion increased by a
      factor of 2.3 on the 6 degrees cross slope (P=.000). CONCLUSIONS: Users must push
      harder when on a cross slope. This increased loading is borne by the users' arms,
      which are at risk for overuse injuries. Exposure to biomechanic loading can be
      reduced by avoiding cross slopes when possible.

PMID- 17207680
TI  - Stroke pattern and handrim biomechanics for level and uphill wheelchair
      propulsion at self-selected speeds.
AB  - OBJECTIVES: To investigate the natural stroke patterns of wheelchair users
      pushing on a level surface, to determine if users adapt their stroke patterns for
      pushing uphill, and to assess whether there are biomechanic advantages to one or
      more of the stroke patterns. DESIGN: Case series. SETTING: Biomechanics
      laboratory. PARTICIPANTS: Twenty-six manual wheelchair users with a spinal cord
      injury. INTERVENTION: Subjects pushed their own wheelchairs at self-selected
      speeds on a research treadmill set to level, 3 degrees , and 6 degrees grades.
      Stroke patterns were measured using a motion capture system. Handrim biomechanics
      were measured using an instrumented wheel. MAIN OUTCOME MEASURES: Stroke patterns
      were classified for both level and uphill propulsion according to 1 of 4 common
      classifications: arcing, semi-circular, single-looping (SLOP), and double-looping
      (DLOP). Biomechanic outcomes of speed, peak handrim force, cadence, and push
      angle were all compared across stroke classifications using an analysis of
      variance. RESULTS: Only 3 of the 4 stroke patterns were observed. None of the
      subjects used the semi-circular pattern. For level propulsion, the stroke
      patterns were fairly balanced between arcing (42%), SLOP (31%), and DLOP (27%).
      Subjects tended to change their stroke pattern for pushing uphill, with 73% of
      the subjects choosing the arcing pattern by the 6 degrees grade. No statistically
      significant differences were found in handrim biomechanics or subject
      characteristics across stroke pattern groups. CONCLUSIONS: Wheelchair users
      likely adapt their stroke pattern to accommodate their propulsion environment.
      Based on the large percentage of subjects who adopted the arcing pattern for
      pushing uphill, there may be benefits to the arcing pattern for pushing uphill.
      In light of this and other recent work, it is recommended that clinicians not
      instruct users to utilize a single stroke pattern in their everyday propulsion
      environments.

PMID- 17207681
TI  - The Foot Posture Index: Rasch analysis of a novel, foot-specific outcome measure.
AB  - OBJECTIVE: To investigate the internal construct validity of a clinician-assessed
      measure of foot position, the Foot Posture Index (FPI), versions FPI-8 and FPI-6.
      DESIGN: Rasch analysis of baseline FPI scores from studies conducted during the
      development of the instrument. SETTING: A community-based and a hospital-based
      study, conducted at 2 institutions. PARTICIPANTS: Measures were obtained from 143
      participants (98 men, 45 women; age range, 8-65y). INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Rasch analysis was undertaken using RUMM2020 software in
      order to evaluate the following properties of the FPI: unidimensionality of each
      item included in the FPI, the differential item functioning (DIF) of each item,
      and item and person separation indices. RESULTS: In the developmental draft of
      the instrument, the 8-item FPI-8 showed some misfit to the Rasch model
      (chi(16)(2) test=27.63, P=.03), indicating lack of unidimensionality. Two items
      were identified as problematic in the Rasch modeling: Achilles' tendon insertion
      (Helbing's sign), which showed illogical response ordering and "congruence of the
      lateral border of the foot," which showed misfit, indicating that this item may
      be measuring a different construct (chi(2)(2) test=15.35, P<.01). All FPI-8 items
      showed an absence of DIF, and the person separation index (PSI) was good
      (PSI=.88). The revised FPI-6, which does not include the 2 problematic items,
      showed unidimensionality (chi(12)(2) test=11.49, P=.49), indicating a good
      overall fit to the model, and improvement over the preliminary version. With the
      removal of the 2 problematic items, there were no disordered thresholds; all
      items remained DIF free and all individual items displayed a good fit to the
      model. The person-separation index for the FPI was similar for both the 8-item
      (FPI-8=.880) and 6-item (FPI-6=.884) versions. CONCLUSIONS: The original FPI-8
      showed significant mismatching to the model. The 2 items in the FPI-8 that were
      identified as problematic in clinical validation studies were also found to be
      contributing to the lack of fit to the Rasch model. The finalized 6-item
      instrument showed good metric properties, including good individual item fit and
      good overall fit to the model, along with a lack of differential item
      functioning. This analysis provides further evidence for the validity of the FPI
      6 as a clinical instrument for use in screening studies and shows that it has the
      potential to be analyzed using parametric strategies.

PMID- 17207682
TI  - Assessments of interrater reliability and internal consistency of the Norwegian
      version of the Berg Balance Scale.
AB  - OBJECTIVE: To investigate the interrater reliability and the internal consistency
      of the Norwegian version of the Berg Balance Scale (BBS) when applied to patients
      in a geriatric department. DESIGN: Interrater reliability was measured using the
      kappa statistics and intraclass correlation coefficients (ICCs). SETTING:
      Geriatric rehabilitation unit and geriatric day hospital in Norway. PARTICIPANTS:
      Eighty-three patients were included; 25 were inpatients in a geriatric
      rehabilitation unit, whereas 58 were admitted to a geriatric day hospital.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The BBS. RESULTS: The kappa
      values for the different BBS items varied from 0.83 to 1.00, and the ICC for the
      sum score of the BBS was .998 (95% confidence interval, .996-.999). The mean
      value of the BBS was 44.4. There was a negative significant relation between age
      and the sum score (r=-.36). The sum scores of BBS ranged from 12 to 56. The
      patients were able to perform the BBS without ceiling effect. The score values 3
      and 4 were more frequently used than the score values 0, 1, and 2. CONCLUSIONS:
      The Norwegian version of the BBS seems to have an excellent interrater
      reliability and high internal consistency when applied to patients in geriatric
      rehabilitation.

PMID- 17207683
TI  - The reliability and validity of the Four Square Step Test for people with balance
      deficits secondary to a vestibular disorder.
AB  - OBJECTIVE: To determine the reliability and validity of the Four Square Step Test
      (FSST) for use in people with balance deficits secondary to vestibular disorders,
      who frequently report falling and have difficulty with changes of direction.
      DESIGN: Cross-sectional descriptive study. SETTING: Outpatient clinic.
      PARTICIPANTS: Thirty-two people with balance deficits secondary to vestibular
      disorders (mean age, 63.7+/-17.8y) who were currently enrolled in a vestibular
      physical therapy program agreed to participate. INTERVENTIONS: Participants
      performed the FSST, the Timed Up & Go (TUG) test, an 11-m walk test during which
      walking speed was recorded, and the Dynamic Gait Index (DGI) and completed the
      Dizziness Handicap Inventory (DHI) and the Activities-Specific Balance Confidence
      (ABC) Scale. MAIN OUTCOME MEASURES: The main outcome measures were the FSST time,
      TUG results, DGI score, gait velocity, and DHI and ABC scores. Number of fall
      risk factors, as determined by published scores for people at risk for falling on
      the TUG test and gait speed, and number of falls were compared with FSST scores.
      RESULTS: The FSST has good reliability (intraclass correlation coefficient, model
      3,1: .93; 95% confidence interval, .86-.96) and had good correlations with the
      other gait measures (correlation coefficients for the TUG, .69; gait speed, .65;
      DGI, -.51) and poor correlations with the DHI and the ABC (DHI, -.13; ABC, -.12).
      Multivariate linear regression showed that 51.5% of FSST performance was
      explained by TUG score and gait speed. The mean FSST time differed significantly
      between groups with 0 (n=12), 1 (n=12), or 2 to 3 (n=8) risk factors for falls
      (analysis of variance, F=10.02; P<.01). A cutoff score of greater than 12 seconds
      on the FSST was associated with a sensitivity of 80% and specificity of 92% for
      the identification of subjects with 1 or more risk factors for falls.
      CONCLUSIONS: The FSST is a reliable and valid tool for measuring the ability to
      perform multidirectional movements in people with balance deficits secondary to
      vestibular disorders.

PMID- 17207684
TI  - Effect of attention focus on acquisition and retention of postural control
      following ankle sprain.
AB  - OBJECTIVE: To examine the effect of attentional focus instructions and dynamic
      balance training on ankle sprain recovery. DESIGN: Randomized controlled trial.
      SETTING: Outpatient physical therapy department. PARTICIPANTS: Forty volunteers
      (age range, 19-33y) referred to treatment within 4 months after sustaining a
      grade 1 or 2 ankle sprain with no concurrent impairments. Participants were
      randomly allocated to 1 of 2 groups differing in training instructions.
      INTERVENTION: Postural control training consisted of ten 20-second trials,
      performed on 3 consecutive days, at 2 stability levels of the Biodex Stability
      System (BSS). Training instructions directed the participants to either an
      internal or an external focus of attention. Assessments were conducted on the BSS
      pre- and post-training, and 48 hours after the last session (retention test).
      MAIN OUTCOME MEASURES: Overall stability as indicated by variance in platform
      displacement in all directions; anteroposterior (AP) variance of platform
      displacement; and mediolateral variance of platform displacement. RESULTS:
      Increases in overall and AP stability were observed immediately following
      training in both groups and were maintained at the retention test. Interaction
      effect indicates greater improvement in the external-focus group. CONCLUSIONS:
      Our results suggest that external focus of attention is advantageous for the
      learning of a postural control task following an ankle injury.

PMID- 17207685
TI  - Clinical identification of multiple fall risk early after unilateral transtibial
      amputation.
AB  - OBJECTIVE: To examine if previously reported clinical tests of stepping and
      functional mobility could discriminate between multiple-falling and nonmultiple
      falling people with unilateral transtibial amputations. DESIGN: Nonrandomized
      prospective cohort. SETTING: Rehabilitation hospital and general community.
      PARTICIPANTS: Forty-seven subjects initially recruited and tested at discharge.
      Forty subjects were retested at 6 months postdischarge and grouped as either
      multiple fallers (n=13) or nonmultiple fallers (n=27). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Four Square Step Test (FSST), Timed Up & Go
      (TUG) test, 180 degrees turn test, and the Locomotor Capabilities Index (LCI)
      advanced score. RESULTS: Significant differences (P<.01) were found between the 2
      groups for all of the main outcome measures. The test scores associated with an
      increased risk of having multiple falls were as follows: TUG test of 19 seconds
      or more (sensitivity, 85%; specificity, 74%), turn time of 3.7 seconds or more
      (sensitivity, 85%; specificity, 78%), turn steps 6 steps or more (sensitivity,
      100%; specificity, 74%), FSST of 24 seconds or more (sensitivity, 92%;
      specificity, 93%), and LCI advanced score of 15 or less (sensitivity, 43%;
      specificity, 91%). CONCLUSIONS: In this study, multiple-falling people with
      transtibial amputations displayed impaired mobility on the outcome measures
      reported. These measures offer valuable clinical tests of different and
      functionally relevant activities and provide good identification of multiple
      falls risk.

PMID- 17207686
TI  - Determinants of walking function after stroke: differences by deficit severity.
AB  - OBJECTIVES: To investigate the relationship of cardiovascular fitness
      (Vo(2)peak), neurologic deficits in balance and leg strength, and body
      composition to ambulatory function after stroke and to determine whether these
      relationships differ between those with milder versus more severe gait deficits.
      DESIGN: Cross-sectional correlation study. SETTING: Outpatient clinic of an
      academic medical center. PARTICIPANTS: Seventy-four people (43 men, 31 women;
      mean age +/- standard deviation, 64+/-10y) with chronic hemiparetic stroke.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Thirty-foot (9.1-m) walk
      velocity, 6-minute walk distance, Vo(2)peak, Berg Balance Scale score, bilateral
      quadriceps eccentric torque, total and regional lean mass, and percentage of fat
      mass. RESULTS: Short-distance walking correlated significantly with
      cardiovascular fitness, balance, paretic leg strength, nonparetic leg strength,
      percentage of body fat, and paretic lean mass but not with nonparetic lean mass.
      Long-distance walking correlated significantly with cardiovascular fitness,
      balance, paretic leg strength, nonparetic leg strength, and paretic lean mass but
      not with percentage of body fat or nonparetic lean mass. Stepwise regression
      showed that cardiovascular fitness, balance, and paretic leg strength were
      independently associated with long-distance walking (r(2)=.60, P<.001). Variance
      in long-distance walking was largely explained by balance for those who walked
      more slowly (<.48m/s) for short distances (r(2)=.42, P<.001) and by
      cardiovascular fitness for those who walked more quickly (>.48m/s) for short
      distances (r(2)=.26, P=.003). CONCLUSIONS: Short-distance walking after stroke is
      related to balance, cardiovascular fitness, and paretic leg strength. Long
      distance walking ability differs by gait deficit severity, with balance more
      important in those who walk more slowly and cardiovascular fitness playing a
      greater role in those who walk more quickly. Improved understanding of the
      factors that predict ambulatory function may assist the design of individualized
      rehabilitation strategies across the spectrum of gait deficit severity in those
      with hemiparetic stroke.

PMID- 17207687
TI  - Proximally placed alignment control strap for ankle varus deformity: a case
      report.
AB  - Ankle varus is a commonly encountered deformity in patients with neurologic or
      musculoskeletal disorders. It impedes stability during the stance phase of gait
      and often causes skin lesions on the lateral ankle area. Plastic or conventional
      ankle-foot orthoses (AFOs) with supplementary features such as a T-strap or
      increased contact area of the lateral flange have been used for correctable varus
      deformities. These supplementary modifications, however, have limitations as
      effective tools for varus control, and ankle varus may persist despite their use.
      We are revisiting the concept of a proximally placed alignment control strap for
      ankle varus, which may overcome the limitations of currently available
      modifications. This alignment control strap is designed to provide a medially
      directed force on the tibia and fibula against the force of varus deformation of
      the ankle. This modification can be easily added to various types of existing
      AFOs with acceptable aesthetic appearance. We describe 2 cases of manually
      correctable but persistent varus deformities of the ankle that were successfully
      controlled by utilization of the proximally placed alignment control strap.

PMID- 17207688
TI  - Analysis of effective radiating area, power, intensity, and field characteristics
      of ultrasound transducers.
AB  - OBJECTIVE: To characterize the ultrasound fields produced by a cohort of
      transducers from a single manufacturer via hydrophone and Schlieren technology.
      DESIGN: Descriptive study. SETTING: Measurement laboratory. PARTICIPANTS: Seven
      same-model ultrasound transducers from a single manufacturer. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Effective radiating area (ERA), total power,
      spatial average intensity (SAI), beam nonuniformity ratio (BNR), and Schlieren
      beam widths at 1.0 and 3.3 MHz. RESULTS: Values for ERA (1.0 MHz range, 3.62-4.38
      cm(2); 3.3 MHz range, 3.74-4.76 cm(2)), total power (1.0 MHz range, 5.0-5.6 W;
      3.3 MHz range, 4.7-5.7 W), SAI (1.0 MHz range, 1.2-1.4 W/cm(2); 3.3 MHz range,
      1.0-1.5 W/cm(2)), and BNR (1.0 MHz range, 2.79-5.85; 3.3 MHz range, 2.51-4.56)
      fell within manufacturer's specifications and U.S. Food and Drug Administration
      (FDA) regulations. Schlieren analysis showed significantly larger beam widths at
      3.3 MHz compared with 1.0 MHz and a large degree of variability in the ultrasound
      fields generated by the different transducers. There were no significant
      correlations between beam widths and ERA values. CONCLUSIONS: ERA and total power
      values in a test cohort exist within a range that met FDA regulations. Individual
      variability in ERA and total power resulted in 50% variability in SAI. This
      variability may help explain previous reports of heating differences between
      transducers.

PMID- 17207690
TI  - Does exercise training during hemodialysis really improve dialysis efficacy?

PMID- 17207691
TI  - PET/CT in non-small cell lung cancer staging-promises and problems.
AB  - Integrated positron emission tomography/computed tomography (PET/CT) has many
      advantages over solitary PET and CT, which has led it to become an increasingly
      established imaging technique in the management of many cancers. This article
      will review the evidence for the role of (18)F-fluorodeoxyglucose PET/CT in non
      small cell lung cancer staging, examining its strengths, weaknesses and cost
      effectiveness.

PMID- 17207692
TI  - The clinical value of proton magnetic resonance spectroscopy in adult brain
      tumours.
AB  - Proton magnetic resonance spectroscopy (1H MRS) non-invasively provides
      information on the biochemical profile (typically including up to nine
      metabolites and mobile lipids) of brain tissue, which varies according to the
      underlying disease process. A number of studies have assessed its accuracy in the
      diagnosis of adult brain tumours. This article describes the basic principles of
      1H MRS, the metabolic profiles of different brain tumours, and practical points
      to aid interpretation of spectra. The literature is reviewed regarding the role
      of 1H MRS in the diagnosis of brain tumours and more specifically where it has
      proven to be of additional benefit over conventional magnetic resonance imaging.

PMID- 17207693
TI  - Open-source software for radiologists: a primer.
AB  - There is a wide variety of free (open-source) software available via the Internet
      which may be of interest to radiologists. This article will explore the use of
      open-source software in radiology to help streamline academic workflow and
      improve general efficiency and effectiveness by highlighting a number of the most
      useful applications currently available. These include really simple syndication
      applications, e-mail management, spreadsheet, word processing, database and
      presentation packages, as well as image and video editing software. How to
      incorporate this software into radiological practice will also be discussed.

PMID- 17207694
TI  - Oncoradiology.
AB  - This is the seventh in a series of short reviews of internet-based radiological
      educational resources and will focus on oncological radiology. What follows is a
      list of carefully selected websites to save you time searching them out for
      yourself. Most of the sites cater for trainee or non-specialist radiologists but
      may also be of interest to oncology trainees and specialists for use in teaching.
      Hyperlinks are available in the electronic version of this article.

PMID- 17207695
TI  - Antenatal renal pelvic dilatation; the long-term outlook.
AB  - AIM: The purpose of this study was twofold: first to provide data for more
      accurate counselling of parents with regard to prognosis, and second, to ensure
      that by following a policy of selective micturating cystourethography (MCUG),
      significant pathology is not missed, in particular vesicoureteric reflux (VUR).
      (MCUG is only undertaken if the renal pelvic diameter (RPD) is >/= 10 mm or if
      there is calyceal or ureteric dilatation.) MATERIAL AND METHODS: Data were
      collected prospectively over a 6-year period. Pre and postnatal imaging findings
      were collected for all infants in whom a RPD of >/= 5 mm was identified at any
      gestational age. The imaging records of all patients were reviewed in 2005 for
      evidence of pathology detected after re-presentation with symptoms. The age range
      at review varied from 2-8 years. RESULTS: Complete data were available in 527
      infants. The risk of significant pathology was related to the degree of antenatal
      renal pelvic dilatation varying from 6% for a RPD of 5 mm at 20 weeks gestation
      to 38% at 10 mm. At 28-33 weeks gestation the risk varied from 5% at 5mm to 15%
      at 10 mm. Subsequent imaging record review revealed only one patient with grade
      II VUR in the study population not picked up by our selective MCUG policy.
      CONCLUSION: The present study provides prognostic information that can be given
      to parents both antenatally and postnatally, and reassurance that a selective
      MCUG policy is appropriate.

PMID- 17207696
TI  - The value of in-utero magnetic resonance imaging in ultrasound diagnosed foetal
      isolated cerebral ventriculomegaly.
AB  - AIM: To assess whether magnetic resonance imaging (MRI) is a useful adjunct to
      ultrasound (US) when imaging cases of foetal isolated cerebral ventriculomegaly.
      To assess whether, in such cases, ventricular morphology is a useful indicator
      for the underlying pathology, as has recently been suggested. MATERIALS AND
      METHODS: A retrospective analysis was undertaken of 30 cases of isolated
      ventriculomegaly diagnosed using US and referred for in utero MRI. The
      gestational age of each case was noted and the MRI report. Both ventricles were
      measured and each case was categorized according to severity and morphology. The
      MRI report was compared to the final diagnosis. RESULTS: Of the 30 cases
      evaluated 18 had mild ventriculomegaly (<15 mm; gestational age range 20-31
      weeks, mean 22.8, median 22) and 12 had severe ventriculomegaly (>15 mm;
      gestational age range 21-37 weeks, mean 28, median 28.5). Additional
      abnormalities were found in 50% of cases overall (44% mild, 58% severe) using
      MRI. CONCLUSIONS: Using MRI additional abnormalities were identified in 50% of
      the foetuses. The morphology of the cases did not suggest underlying pathology in
      this group. In utero MRI is a useful adjunct to US in cases of foetal cerebral
      ventriculomegaly referred after initial diagnosis using US.

PMID- 17207697
TI  - CT colonography: automatic measurement of polyp diameter compared with manual
      assessment - an in-vivo study.
AB  - AIM: To investigate whether automated diameter assessment was feasible for CT
      colonography. MATERIALS AND METHODS: Two experienced observers independently
      measured the maximum diameter of 50 polyps (colonoscopic reference size range 5
      12 mm) from colonography datasets using conventionally placed software callipers
      and a variety of two-dimensional (2D) computed tomography (CT) window settings
      (colon, abdominal, bone, lung), and also three-dimensional (3D) perspective
      rendering. Polyps were also measured using automated polyp-segmentation software.
      Agreement between observers and with the colonoscopic reference measurement was
      determined using Bland-Altman, Wilcoxon, and Mann-Whitney U analyses. RESULTS:
      Inter-observer agreement was similar for all window displays: mean difference in
      millimetres (SD difference; 95% limits of agreement) ranged from 0 (1.7, -3.3,
      3.3) for 2D colon to -1.1mm (1.6, -4.3, 2.0) for 3D, compared with -0.5 (2.09, 
      4.6, 3.6) for automated measurement. When compared to colonoscopy, the largest
      discrepancy occurred using the 3D display (mean difference 1.3mm, 2.5mm for each
      observer). There was also a significant difference between estimates and
      reference size when using the 2D abdominal and 3D displays (p=0.03, <0.001).
      CONCLUSION: Automated polyp measurement is possible in vivo. Automated and
      conventional methods have comparable inter-observer agreement. The greatest
      measurement error is encountered when using a 3D display for estimates of
      diameter.

PMID- 17207698
TI  - Bronchiectasis: correlation of high-resolution CT findings with health-related
      quality of life.
AB  - AIM: To evaluate the relationship between the severity of bronchiectatic
      diseases, as evident on high-resolution computed tomography (HRCT) and the
      patient's quality of life measured using the St George's Respiratory
      Questionnaire (SGRQ). METHODS AND MATERIALS: Forty-six patients (25 women, 21
      men, mean age: 63 years) with bronchiectatic disease as evident on recent HRCT
      examinations were recruited. Each patient completed the SGRQ and underwent
      respiratory function tests. HRCT findings were blindly and independently scored
      by two radiologists, using the modified Bhalla scoring system. The relationships
      between HRCT scores, SGRQ scores and pulmonary function tests were evaluated.
      RESULTS: The patients' total CT score did not correlate with the SGRQ scores.
      However, patients with more advanced disease on HRCT, significantly differed in
      their SGRQ scores from patients with milder bronchiectatic disease. A significant
      correlation was found between the CT scores for the middle and distal lung zones
      and the activity, impacts and total SGRQ scores. No correlation was found between
      CT scores and respiratory function test indices. However, a significant
      correlation was found between the SGRQ scores and most of the respiratory
      function test indices. CONCLUSION: A correlation between the severity of
      bronchiectatic disease as expressed in HRCT and the health-related quality of
      life exists in patients with a more severe bronchiectatic disease but not in
      patients with mild disease. Such correlation depends on the location of the
      bronchiectasis in the pulmonary tree.

PMID- 17207699
TI  - MRI for the demonstration of subclinical muscle involvement in muscular
      dystrophy.
AB  - AIM: To compare magnetic resonance imaging (MRI) with clinical examination for
      the detection of muscle abnormality in patients with muscular dystrophy. METHODS:
      Muscle power in 20 patients with a variety of forms of muscular dystrophy was
      examined clinically using the Medical Research Council (MRC) grading scale, and
      patients were subsequently imaged with MRI. MRI and clinical examination for the
      detection of muscle normality and abnormality were compared using a McNemar chi
      squared test to examine differences between the two methods. RESULTS: MRI
      demonstrated radiological evidence of muscle abnormality more often than clinical
      examination; 50% of movements assessed as normal on clinical examination were
      associated with muscle abnormalities on MRI, including a significant proportion
      where there was severe radiological abnormality, indicating that focally advanced
      disease may be undetectable clinically. CONCLUSION: The combination of clinical
      examination and MRI could improve the accuracy of phenotypic characterization of
      patients with muscular dystrophy, and this in turn could allow a more focussed
      molecular analysis through muscle biopsy or genetic investigation. This may also
      be very helpful in the assessment of the degree of muscle compromise not only in
      the early phases of the disease but especially during follow-up and can be used
      in therapeutic trials.

PMID- 17207700
TI  - CT-guided procedures: evaluation of a phantom system to teach accurate needle
      placement.
AB  - AIM: To evaluate the use of a phantom system to help teach the basic techniques
      of accurate CT-guided needle placement, thereby avoiding the risks associated
      with teaching on patients. MATERIALS AND METHODS: Gelatine phantoms with five,
      1.9 cm embedded spherical wooden targets were constructed. Four trainee operators
      performed 15 simulated biopsy procedures on the targets (series one) and repeated
      identical procedures 2 weeks later (series two). Statistical analysis of accuracy
      of needle placement and subject confidence were performed. RESULTS: Significant
      sequential improvement in axial plane angular error was noted with the average
      error decreasing by 0.33 degrees after every five procedures performed (95% CI: 
      0.58 to -0.08, p=0.01). Operator confidence indicated significant improvement
      both within each series and from series one to series two (95% CI: 0.08 to 1.17,
      p=0.025 and 95% CI: 0.00 to 0.58, p=0.05) respectively. However, variability in
      operator performance made statistically significant improvement in other
      variables unproven. CONCLUSION: Despite the study comprising a relatively small
      number of participants and procedures, it clearly demonstrated the effectiveness
      of teaching operators to perform CT-guided procedures using a phantom system.
      Needle placement accuracy significantly improved, with a reduction in axial
      angular error, and improved operator confidence without the risks associated with
      training on patients. Three of the operators in this study had never performed a
      CT-guided procedure previously, and their proficiency, after a relatively short
      but intense period of training, was impressive. The use of phantoms should be
      considered routinely for basic training of CT-guided needle placement.

PMID- 17207701
TI  - Myelopathy due to intrathecal chemotherapy: magnetic resonance imaging findings.

PMID- 17207702
TI  - Bladder carcinoma recurrence post-cystectomy simulating rectal carcinoma.

PMID- 17207703
TI  - Late presentation of developmental dysplasia of the hip following normal
      ultrasound examination.

PMID- 17207704
TI  - Reversed flow in the left internal jugular vein on time-of-flight MRA as a sign
      of innominate vein compression syndrome.

PMID- 17207705
TI  - Middle mediastinal neurogenic tumour: an unusual cause of a hoarse voice.

PMID- 17207706
TI  - Re: "Scrotal varicocoele, exclude a renal tumour". Is this evidence based?

PMID- 17207707
TI  - HLA-G is found in lipid rafts and can act as a signaling molecule.
AB  - HLA-G protein is the functional homolog of Qa-2, the product of the mouse
      preimplantation embryo development (Ped) gene. Embryos expressing Qa-2 on the
      cell surface exhibit a faster rate of preimplantation cleavage and preferential
      survival in utero compared with Qa-2-negative embryos. Qa-2 is
      glycosylphosphatidylinositol (GPI) linked in the cell membrane. As a result, Qa-2
      proteins cluster in cholesterol- and sphingolipid-rich lipid raft microdomains in
      the cell membrane and can signal via raft-associated intracellular signaling
      molecules. Using T cells as a model system, cross-linking of Qa-2 on the cell
      membrane has been shown to induce proliferation of resting cells. HLA-G, like Qa
      2, lacks a cytoplasmic domain capable of transducing signals from the cell
      surface to the nucleus, but unlike Qa-2, HLA-G has a short six-amino acid
      cytoplasmic tail rather than a GPI anchor. To test whether HLA-G, like Qa-2, is
      located in lipid rafts and can act as a signaling molecule, we used an HLA-G
      transgenic mouse system. T cells were isolated and tested for HLA-G expression by
      immunofluorescence and for localization of HLA-G in lipid rafts by
      immunofluorescence and Western blotting. Next, the T cells were cross-linked with
      anti-HLA-G antibody to test for induction of proliferation. Our novel results
      show that HLA-G, like GPI-linked Qa-2, is present in lipid rafts in the cell
      membrane and can act as a signaling molecule to induce proliferation of resting T
      cells.

PMID- 17207708
TI  - HLAMatchmaker: a molecularly based algorithm for histocompatibility
      determination. V. Eplet matching for HLA-DR, HLA-DQ, and HLA-DP.
AB  - This report describes the design of the eplet version of HLAMatchmaker to
      determine class II compatibility at the structural level. This matching algorithm
      is based on the hypothesis, developed from molecular modeling of crystallized
      antigen-antibody complexes, that functional epitopes are represented by patches
      of surface-exposed nonself-amino acid residues surrounded by residues within a 3
      A radius. Patch determinations with a molecular viewer of crystalline structural
      models downloaded from the Entrez Molecular Modeling Database Web site led to the
      identification of 44 DRB, 33DQB, 29 DQA, 20 DPB, and 9 DPA unique combinations of
      polymorphic positions. The residue compositions of these patches were then
      determined from amino acid sequences. This analysis resulted in a repertoire of
      146 DRB, 74 DQB, 58 DQA, 45 DPB, and 19 DPA eplets. In many eplets, the residues
      are in short linear sequences, but many other eplets have discontinuous sequences
      of residues that cluster on or near the molecular surface. This analysis has also
      shown that all serologically defined DR and DQ antigens detectable by
      monospecific antibodies have unique eplets. Other eplets are present in groups of
      class II antigens, many of which appear as cross-reacting. The eplet version of
      HLAMatchmaker should be considered as a hypothetical model for the structural
      assessment of donor-recipient compatibility and the determination of mismatch
      acceptability for sensitized patients. This computer algorithm can be downloaded
      from the HLA Matchmaker Webside at http://tpis.upmc.edu.

PMID- 17207709
TI  - Histocompatibility class I and II antigens in extensive kindred with Sneddon's
      syndrome and related hypercoagulation disorders.
AB  - We have studied the relationship between the histocompatibility class I and II
      antigens and Sneddon's syndrome (SS) in a Spanish patient with SS and her
      relatives (13 available members of an extensive 3-generation pedigree with
      diverse autoimmune hypercoagulation abnormalities). The patient and her father
      were diagnosed with a primary antiphospholipid antibody syndrome and were HLA-A30
      B13-Bw6. In addition, a HLA-Bw6-DQ1 association was present in all the members of
      this kindred. These data suggest that the combination of the histocompatibility
      class I and II antigens in this family may be a marker for predisposition to SS.

PMID- 17207710
TI  - A high degree of HLA disparity arises from limited allelic diversity: analysis of
      1775 unrelated bone marrow transplant donor-recipient pairs.
AB  - The allelic diversity and associated human leukocyte antigen (HLA) disparity of
      1775 bone marrow recipients and their unrelated donors, matched for six of six
      (1361/1775,77%), five of six (397/1775, 22%), or four of six (17/1775, 1%) HLA-A,
      -B, -DR antigens, were retrospectively evaluated. The comprehensive HLA analysis
      included the class I (A, B, C) and II (DRB1, DQA1, DQB1, DPA1, DPB1) loci. Most
      (>66%) of the predominantly Caucasian study population carried one or two of five
      to seven common alleles at each HLA locus. In spite of this limited diversity,
      29% of the six of six antigen-matched transplants carried allele mismatches at
      HLA-A, -B, and/or -DRB1, and 92% carried at least one allele mismatch at one of
      the eight HLA loci tested. Of the 968 HLA-A,-B,-DRB1 allele-matched pairs, 89%
      carried mismatches at other HLA loci, predominantly at DP loci. The substantially
      greater than expected HLA allelic disparity between donor and recipient suggests
      extensive haplotypic diversity and underscores the importance of enhancing
      approaches to mitigate the deleterious effect of HLA mismatches.

PMID- 17207711
TI  - Variable number of tandem repeats of TNF receptor type 2 promoter as genetic
      biomarker of susceptibility to develop invasive pulmonary aspergillosis.
AB  - Tumor necrosis factor alpha (TNF-alpha) and lymphotoxin alpha (LT-alpha) are
      pivotal mediators of inflammatory responses in fungal infection diseases. We
      hypothesized that polymorphisms in genes of these cytokines or their receptors
      might increase the susceptibility of hematologic patients to develop invasive
      pulmonary aspergillosis (IPA). One hundred two hematologic patients and 124 age
      matched controls were enrolled in the study, and the following standard single
      nucleotide polymorphisms were investigated: TNF-alpha -308 and +489, LT-alpha
      +252 and Tumor Necrosis Factor Receptor 2 (TNFR2) +676. Variable number of tandem
      repeats (VNTRs) at position -322 of the TNFR2 gene were also studied. Genotypic
      and allelic frequencies were similar between patients and controls. IPA was
      diagnosed in 54 of the 102 patients according to consensus criteria published by
      the European Organization for Research and Treatment of Cancer/Invasive Fungal
      Infections Cooperative Group. TNF-alpha and LT-alpha polymorphisms were not
      associated with presence of IPA. Susceptibility to IPA was strongly associated
      with VNTR at position -322 in the promoter region of the TNR2 gene (p = 0.029)
      but was not associated with the presence of TNFR2 +676 polymorphism. A genetic
      difference in TNFR2 promoter VNTR may play a major role in susceptibility to IPA
      infection.

PMID- 17207712
TI  - Impact of recipient HLA-C in liver transplant: a protective effect of HLA-Cw*07
      on acute rejection.
AB  - The involvement of the human leukocyte antigen (HLA) in liver graft acceptance is
      controversial, but the frequency of acute rejection (AR) remains high in spite of
      the use of the modern immunosuppressive agents. The present study was aimed at
      determining whether an association exists between liver recipient HLA-C
      polymorphism and AR development that could influence graft acceptance. Four
      hundred and forty-six liver recipients and 473 controls were studied within the
      framework of a collaborative study carried out by the Spanish Transplant
      Immunotolerance Group (RED-GIT). HLA-A and -B were typed by the standard
      microlymphocytotoxicity technique, and HLA-C by polymerase chain reaction
      sequence-specific oligonucleotide probes (PCR-SSOP). A statistically significant
      decrease in the HLA-Cw*07 allele frequency was found in liver recipients
      suffering AR episodes compared to those without AR (NAR). Studies regarding the
      possible influence of the Asn80 and Lys80 epitopes showed that the Asn80 epitope
      also could be associated with AR. However, further analysis considering Asn80
      alleles others than HLA-Cw*07, confirmed that the apparent protective effect of
      the Asn80 epitope was actually from the HLA-Cw*07 allele. In conclusion, the HLA
      Cw*07 allele carried by the liver recipient is negatively associated with AR
      development, and could be considered a predictive factor for liver graft
      acceptance.

PMID- 17207713
TI  - DQB1*0301 and DQB1*0601 modulate narcolepsy susceptibility in Koreans.
AB  - The association of narcolepsy with HLA-DQB1*0602 is established in Japanese,
      African-Americans, European, and North American Caucasians. We examined DRB1,
      DRB3, DRB4, DRB5, DQA1, and DQB1 in 163 patients with centrally mediated daytime
      sleepiness (100 with narcolepsy) and 211 Korean controls. In this population, the
      DQB1*0602 association was always evident in the context of the DRB1*1501
      DQA1*0102-DQB1*0602 haplotype. The DQB1*0602 association was highest in cases
      with hypocretin deficiency (100% vs 13% in controls), most of which had
      narcolepsy-cataplexy (81%). A weaker DQB1*0602 (45%) association was present in
      cases without cataplexy. No human leukocyte antigen (HLA) association was present
      in idiopathic hypersomnia or in cases with normal cerebrospinal fluid (CSF)
      hypocretin-1. As in other populations, DQB1*0602 homozygosity increased risk in
      cases with cataplexy and/or hypocretin deficiency (odds ratio = 2.0 vs
      heterozygotes). Non-DQB1*0602 allelic effects were also observed but could not be
      interpreted in the context of DQB1*0602 overabundance and linkage disequilibrium.
      We therefore next analyzed compound heterozygote effects in 77 subjects with
      either hypocretin deficiency or cataplexy and one copy of DRB1*1501-DQA1*0102
      DQB1*0602, a sample constructed to maximize etiologic homogeneity. In this
      analysis, we found additional predisposing effects of DQB1*0301 and protective
      effects for DQA1*0103-DQB1*0601. Unexpectedly, the predisposing effects of
      DQB1*0301 were present in the context of various DQA1-bearing haplotypes. A
      predisposing effect of DQA1*0303 was also suggested. These results indicate a
      remarkable consistency in the complex HLA association present in narcolepsy
      across multiple ethnic groups.

PMID- 17207714
TI  - Genetic variations of HLA-DRB1 and susceptibility to Kawasaki disease in
      Taiwanese children.
AB  - Although some previous studies have reported that genetic and immunologic factors
      play important roles in the pathogenesis of Kawasaki disease (KD), the etiologic
      factors of this enigmatic pediatric disease are still poorly understood. The
      purpose of this study was to investigate whether polymorphisms of the human
      leukocyte antigen DRB1 (HLA-DRB1) gene are associated with KD and the development
      of coronary artery lesions (CAL) in Taiwanese children. Genomic DNA was extracted
      from whole blood samples from 145 children with KD and 331 healthy controls. The
      HLA-DRB1 gene was genotyped by polymerase chain reaction (PCR) and sequence-based
      typing assays. We found that the distribution of HLA-DRB1 allele families and
      alleles in children with KD did not differ from that in healthy controls.
      Stratified analysis did not demonstrate any association between particular HLA
      DRB1 allele families or alleles and the development of CAL in children with KD.
      These findings suggest that susceptibility to KD and CAL is not associated with
      the HLA-DRB1 gene in a Taiwanese population. If immunogenetic determinants are
      involved in this disease and its complications in Taiwanese children, they must
      involve genes other than HLA-DRB1.

PMID- 17207715
TI  - Coxibs and heart disease: what we have learned and what else we need to know.
AB  - Since their approval in 1998, the popularity of selective cyclooxygenase-2 (COX2)
      inhibitors has swung from a domination of drug sales to serious disputes about
      their cardiovascular safety. Despite the numerous studies on COX2 inhibitors that
      have emerged, drawing conclusions about their cardiovascular safety has been
      complicated by conflicting results, underpowered clinical trials, and the lack of
      a placebo group and use of post hoc analyses in many trials. Nonetheless, certain
      conclusions can be made with reasonable accuracy. This review addresses the
      controversy in 3 segments. It begins with a discussion of the several mechanisms
      proposed to explain how selective COX2 inhibition impacts the cardiovascular
      system. This is followed by a recount of the several clinical studies that delved
      into the cardiovascular outcomes associated with COX2 inhibitors. Finally,
      answers to key questions are provided to assist the clinician in devising a
      systematic approach to the risk-benefit analysis of COX2 inhibitors in actual
      practice.

PMID- 17207716
TI  - Coronary collateral function long after drug-eluting stent implantation.
AB  - OBJECTIVES: This study was designed to compare coronary collateral function in
      patients after bare-metal stent (BMS) or drug-eluting stent (DES) implantation.
      BACKGROUND: Drug-eluting stents have an inhibitory effect on the production of
      cytokines, chemotactic proteins, and growth factors, and may therefore negatively
      affect coronary collateral growth. METHODS: A total of 120 patients with long
      term stable coronary artery disease (CAD) after stent implantation were included.
      Both the BMS group and the DES group comprised 60 patients matched for in-stent
      stenosis severity of the vessel undergoing collateral flow index (CFI)
      measurement at follow-up and for the duration of follow-up. The primary end point
      of the investigation was invasively determined coronary collateral function 6
      months after stent implantation. Collateral function was assessed by simultaneous
      aortic, coronary wedge, and central venous pressure measurements (yielding CFI)
      and by intracoronary electrocardiogram during balloon occlusion. RESULTS: There
      were no differences between the groups regarding age, gender, body mass index,
      frequency of cardiovascular risk factors, use of cardiovascular drugs, severity
      of CAD, or site of coronary artery stenoses. Despite equal in-stent stenosis
      severity (46 +/- 34% and 45 +/- 36%) and equal follow-up duration (6.2 +/- 10
      months and 6.5 +/- 5.4 months), CFI was diminished in the DES versus BMS group
      (0.154 +/- 0.097 vs. 0.224 +/- 0.142; p = 0.0049), and the rate of collaterals
      insufficient to prevent ischemia during occlusion (intracoronary
      electrocardiographic ST-segment elevation > or =0.1 mV) was higher with 50 of 60
      patients in the DES group and 33 of 60 patients in the BMS group (p = 0.001).
      CONCLUSIONS: Collateral function long after coronary stenting is impaired with
      DES (sirolimus and paclitaxel) when compared with BMS. Considering the protective
      nature of collateral vessels, this could lead to more serious cardiac events in
      the presence of an abrupt coronary occlusion.

PMID- 17207717
TI  - Attenuated coronary collateral function after drug-eluting stent implantation: a
      new downside of drug-eluting stents?

PMID- 17207718
TI  - Plaque composition in the left main stem mimics the distal but not the proximal
      tract of the left coronary artery: influence of clinical presentation, length of
      the left main trunk, lipid profile, and systemic levels of C-reactive protein.
AB  - OBJECTIVES: We sought to investigate whether plaques located in the left main
      stem (LMS) differ in terms of necrotic core content from those sited in the
      proximal tract of the left coronary artery. BACKGROUND: Plaque composition,
      favoring propensity to vulnerability, might be nonuniformly distributed along the
      vessel, which might explain the greater likelihood for plaque erosion or rupture
      to occur in the proximal but not in the distal tracts of the coronary artery or
      in LMS. METHODS: A total of 72 patients were included prospectively; 48 (32 men;
      mean age 57 +/- 11 years; 25 with stable angina and 23 affected by acute coronary
      syndromes) underwent a satisfactory nonculprit vessel investigation through
      spectral analysis of intravascular ultrasound radiofrequency data (IVUS-Virtual
      Histology, Volcano Corp., Rancho Cordova, California). The region of interest was
      subsequently divided into LMS and LMS carina, followed by 6 consecutive
      nonoverlapping 6-mm segments in left anterior descending artery in 34 patients or
      in circumflex artery in 14 patients. RESULTS: Necrotic core content (%): 1) was
      minimal in LMS (median [interquartile range]: 4.6 [2 to 7]), peaked in the first
      6-mm coronary segment (11.8 [8 to 16]; p < 0.01), and then progressively
      decreased distally; 2) was overall greater in patients with acute coronary
      syndromes (11.4 [5.5 to 19.8]) than stable angina (7.3 [3.2 to 12.9]; p < 0.001);
      3) was largely independent from plaque size; and 4) did not correlate to systemic
      levels of C-reactive protein or lipid profile. CONCLUSIONS: Plaques located in
      the LMS carry minimal necrotic content. Thus, they mimic the distal but not the
      proximal tract of the left coronary artery, where plaque rupture or vessel
      occlusion occurs more frequently.

PMID- 17207719
TI  - Influence of blood pressure on the effectiveness of a fixed-dose combination of
      isosorbide dinitrate and hydralazine in the African-American Heart Failure Trial.
AB  - OBJECTIVES: This study sought to assess the effect of baseline systolic blood
      pressure (SBP) and changes in SBP on the effectiveness of treatment with fixed
      dose combination of isosorbide dinitrate and hydralazine (FDC I/H) in patients
      with heart failure (HF). BACKGROUND: Low SBP is a risk factor for adverse
      outcomes in patients with HF. However, FDC I/H lowered SBP in the A-HeFT (African
      American Heart Failure Trial) and yet prolonged survival. Whether blood pressure
      (BP) lowering is critical to the efficacy of FDC I/H and whether a low BP limits
      its effectiveness is unclear. METHODS: The effects of FDC I/H on SBP and on
      mortality and hospitalization were compared in patients with a low or high
      baseline SBP using multivariable Cox regression models. The interaction between
      the effect of treatment and baseline SBP was examined. RESULTS: Mean +/- SD
      baseline SBP in all of the patients was 126 +/- 18 mm Hg. Patients with baseline
      SBP equal to or below the median (126 mm Hg) had features of more severe HF.
      Baseline SBP equal to or below the median was an independent risk factor for
      death (hazard ratio [HR] 2.09; 95% confidence interval [CI] 1.02 to 4.29) or
      first hospitalization for HF (HR 1.66; 95% CI 1.18 to 2.34). The FDC I/H
      treatment reduced BP in patients with SBP above the median but not in patients
      with SBP below 126 mm Hg. The FDC I/H treatment was associated with a similar
      decrease in mortality or hospitalization for HF in patients with SBP below the
      median and above the median. The effects of FDC I/H on mortality alone were also
      similar. CONCLUSIONS: In A-HeFT, patients with lower SBP had a greater risk but a
      similar relative benefit from the use of FDC I/H as those with higher SBP. The
      FDC I/H treatment did not reduce SBP in patients with low SBP. An asymptomatic
      low SBP should not be considered a contraindication to use of FDC I/H in patients
      with HF.

PMID- 17207720
TI  - Blood pressure in heart failure: a love-hate relationship.

PMID- 17207721
TI  - Elevated pulmonary artery pressure by Doppler echocardiography predicts
      hospitalization for heart failure and mortality in ambulatory stable coronary
      artery disease: the Heart and Soul Study.
AB  - OBJECTIVES: We compared the predictive ability of tricuspid regurgitation (TR)
      and end-diastolic pulmonary regurgitation (EDPR) gradients in outpatients with
      coronary artery disease. BACKGROUND: The TR and EDPR gradients, in conjunction
      with right atrial pressure, provide Doppler estimates of pulmonary artery
      systolic and diastolic pressures. We hypothesized that increases in TR or EDPR
      gradients in stable coronary artery disease would predict heart failure (HF)
      hospitalization or cardiovascular (CV) death. METHODS: We measured TR and EDPR
      gradients in 717 adults with completed outcome adjudications who were recruited
      for the Heart and Soul Study. Odds ratios (ORs) and 95% confidence intervals
      (CIs) were calculated for HF hospitalization, CV death, all-cause death, and the
      combined end point. Multivariate adjustments were made for age, gender, race,
      history of CV or pulmonary disease, functional class, and left ventricular
      ejection fraction. RESULTS: There were 63 HF hospitalizations, 19 CV deaths, and
      86 all-cause deaths at the 3-year follow-up. There were 466 measurable EDPR
      gradients and 573 measurable TR gradients. Age-adjusted ORs for EDPR >5 mm Hg
      predicted HF hospitalization (2.7, 95% CI 1.3 to 5.5, p = 0.006), all-cause death
      (2.5, 95% CI 1.4 to 4.4, p = 0.002), and HF hospitalization or CV death (2.7, 95%
      CI 1.4 to 5.2, p = 0.004). Age-adjusted OR for TR >30 mm Hg predicted HF
      hospitalization (3.4, 95% CI 1.9 to 6.2, p < 0.0001) and HF hospitalization or CV
      death (3.0, 95% CI 1.7 to 5.3, p = 0.0001). Multivariate adjusted OR per 5-mm Hg
      incremental increases in EDPR predicted HF hospitalization or CV death (1.9, 95%
      CI 1.01 to 3.6, p = 0.046) and all-cause death (1.7, 95% CI 1.05 to 2.8, p =
      0.03). Multivariate adjusted OR per 10-mm Hg incremental increases in TR
      predicted HF hospitalization or CV death (1.6, 95% CI 1.1 to 2.4, p = 0.008).
      CONCLUSIONS: Increases in EDPR or TR gradients predict HF hospitalization or CV
      death among ambulatory adults with coronary artery disease.

PMID- 17207722
TI  - Microvolt T-wave alternans identifies patients with ischemic cardiomyopathy who
      benefit from implantable cardioverter-defibrillator therapy.
AB  - OBJECTIVES: This study sought to assess whether implantable cardioverter
      defibrillators (ICDs) have different mortality benefits among patients with
      ischemic cardiomyopathy who screen negative and non-negative (positive and
      indeterminate) for microvolt T-wave alternans (MTWA). BACKGROUND: Microvolt T
      wave alternans has been proposed as an effective tool for risk stratification.
      However, no studies have examined whether ICD benefits differ by MTWA group.
      METHODS: We developed a prospective cohort of 768 patients with ischemic
      cardiomyopathy (left ventricular ejection fraction < or =35%) and no prior
      sustained ventricular arrhythmia, of which 392 (51%) received ICDs. The mean
      follow-up time was 27 +/- 12 months. Propensity scores for ICD implantation based
      on the variables most likely to influence defibrillator implantation were
      developed for each MTWA cohort. Multivariable Cox analyses that controlled for
      propensity score, demographics, and clinical variables evaluated the degree to
      which ICDs decreased mortality risk for each MTWA group. RESULTS: We identified
      514 (67%) patients with a non-negative MTWA test result. After multivariable
      adjustment, ICDs were associated with lower all-cause mortality in MTWA-non
      negative patients (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.27 to
      0.76, p = 0.003) but not in MTWA-negative patients (HR 0.85, 95% CI 0.33 to 2.20,
      p = 0.73) (for interaction, p = 0.04), with the mortality benefit in MTWA-non
      negative patients largely mediated through arrhythmic mortality reduction (HR
      0.30, 95% CI 0.13 to 0.68, p = 0.004). The number needed to treat with an ICD for
      2 years to save 1 life was 9 among MTWA-non-negative patients and 76 among MTWA
      negative patients. CONCLUSIONS: In patients with ischemic cardiomyopathy and no
      prior history of ventricular arrhythmia, mortality reduction with ICD
      implantation differs by MTWA status, with implications for risk stratification
      and health policy.

PMID- 17207723
TI  - Should microvolt T-wave alternans be utilized routinely in selecting patients for
      prophylactic implantable cardioverter-defibrillator insertion in the setting of
      ischemic heart disease?

PMID- 17207724
TI  - Prognostic value of multislice computed tomography coronary angiography in
      patients with known or suspected coronary artery disease.
AB  - OBJECTIVES: This study sought to determine the prognostic value of multislice
      computed tomography (MSCT) coronary angiography in patients with known or
      suspected coronary artery disease (CAD). BACKGROUND: It is expected that MSCT
      will be used increasingly as an alternative imaging modality in the diagnosis of
      patients with suspected CAD. Data on the prognostic value of MSCT, however, are
      currently not available. METHODS: A total of 100 patients (73 men, age 59 +/- 12
      years) who were referred for further cardiac evaluation due to suspicion of
      significant CAD underwent additional MSCT coronary angiography to evaluate the
      presence and severity of CAD. Patients were followed up for the occurrence of: 1)
      cardiac death, 2) nonfatal myocardial infarction, 3) unstable angina requiring
      hospitalization, and 4) revascularization. RESULTS: Coronary plaques were
      detected in 80 (80%) patients. During a mean follow-up of 16 months, 33 events
      occurred in 26 patients. In patients with normal coronary arteries on MSCT, the
      first-year event rate was 0% versus 30% in patients with any evidence of CAD on
      MSCT. The observed event rate was highest in the presence of obstructive lesions
      (63%) and when obstructive lesions were located in the left main (LM)/left
      anterior descending (LAD) coronary arteries (77%). Nonetheless, an elevated event
      rate was also observed in patients with nonobstructive CAD (8%). In multivariate
      analysis, significant predictors of events were the presence of CAD, obstructive
      CAD, obstructive CAD in LM/LAD, number of segments with plaques, number of
      segments with obstructive plaques, and number of segments with mixed plaques.
      CONCLUSIONS: Multislice computed tomography coronary angiography provides
      independent prognostic information over baseline clinical risk factors in
      patients with known and suspected CAD. An excellent prognosis was noted in
      patients with a normal MSCT.

PMID- 17207725
TI  - Cardiovascular manifestations of hyperthyroidism before and after antithyroid
      therapy: a matched case-control study.
AB  - OBJECTIVES: This study sought to prospectively evaluate the prevalence of
      cardiovascular abnormalities in patients with overt hyperthyroidism before and
      after antithyroid therapy. BACKGROUND: Overt hyperthyroidism is associated with
      recognized cardiovascular effects believed to be reversed by antithyroid therapy;
      however, increasing data suggest significant long-term cardiovascular mortality.
      METHODS: A total of 393 (312 women, 81 men) consecutive unselected patients with
      overt hyperthyroidism were recruited and compared with 393 age- and gender
      matched euthyroid control subjects. Hyperthyroid patients were re-evaluated after
      antithyroid therapy. Findings in patients and matched control subjects were
      compared at presentation, after treatment when patients had subclinical
      hyperthyroidism biochemically, and when patients were rendered biochemically
      euthyroid. All had a structured cardiovascular history and examination, including
      measurements of blood pressure (BP) and pulse rate. All had resting 12-lead
      electrocardiogram and 24-h digital Holter monitoring of cardiac rhythm. RESULTS:
      A higher prevalence of cardiovascular symptoms and signs, as well as abnormal
      hemodynamic parameters, was noted among hyperthyroid patients at recruitment
      compared with control subjects. Cardiac dysrhythmias, especially
      supraventricular, were more prevalent among patients than among control subjects.
      Palpitation and dyspnea, postural decrease in systolic pressure, and atrial
      fibrillation (AF) remained more prevalent in treated hyperthyroid subjects with
      subclinical hyperthyroidism compared with control subjects, and remained more
      prevalent after restoration of euthyroidism. Predictors for successful reversion
      to sinus rhythm in those with AF associated with hyperthyroidism were lower BP
      measurements at recruitment and an initial hypothyroid state induced by
      antithyroid therapy. Mortality was higher in hyperthyroid subjects than in
      control subjects after a mean period of follow-up of 66.6 months. CONCLUSIONS:
      Cardiovascular abnormalities are common in patients with overt hyperthyroidism at
      presentation, but some persist despite effective antithyroid therapy.

PMID- 17207726
TI  - Haptoglobin genotype determines myocardial infarct size in diabetic mice.
AB  - OBJECTIVES: We sought to understand the importance of oxidative stress in
      explaining why the haptoglobin (Hp) genotype determines myocardial infarction
      (MI) size in diabetes mellitus (DM). BACKGROUND: Two common alleles (1 and 2)
      exist at the Hp locus in humans. The Hp 2 allele is associated with increased MI
      size in individuals with DM. In vitro, the Hp 2 protein is associated with
      increased generation of oxidatively active iron, whereas the Hp 1 protein is
      associated with increased production of the antioxidant cytokine interleukin (IL)
      10. METHODS: Myocardial infarction was produced by myocardial ischemia
      reperfusion (IR) in DM C57BL/6 mice carrying the Hp 1 or Hp 2 allele. Myocardial
      oxidative stress after IR was assessed using electrospray ionization mass
      spectrometry. Redox active iron and IL-10 were measured in the serum after IR.
      RESULTS: Myocardial infarction size was significantly larger in Hp 2 mice as
      compared with Hp 1 mice (44.3 +/- 9.3% vs. 21.0 +/- 4.0%, p = 0.03), and these
      larger infarctions were associated with a significant increase in a panel of
      hydroxyl-eicosatetraenoic acids. Redox active iron was greater in Hp 2 mice (0.45
      +/- 0.11 micromol/l vs. 0.14 +/- 0.05 micromol/l, p = 0.02), whereas IL-10 was
      greater in Hp 1 mice (85.8 +/- 12.9 pg/microl vs. 46.7 +/- 10.8 pg/microl, p =
      0.04) after IR. Administration of an antioxidant (BXT-51072) to Hp 2 mice reduced
      myocardial injury after IR by more than 80% (p = 0.003), but no myocardial
      protection was provided by the antioxidant to Hp 1 mice. CONCLUSIONS: The
      increased MI size in DM Hp 2 mice occurring after IR may be due to increased
      oxidative stress.

PMID- 17207727
TI  - Systolic and diastolic dyssynchrony in patients with diastolic heart failure and
      the effect of medical therapy.
AB  - OBJECTIVES: The purpose of this study was to determine the prevalence of systolic
      and diastolic dyssynchrony in diastolic heart failure (DHF) patients and identify
      the effects of medical therapy. BACKGROUND: The prevalence of systolic and
      diastolic dyssynchrony in DHF patients is unknown with no data on the effects of
      medical therapy on dyssynchrony. METHODS: Patients presenting with DHF (n = 60;
      61 +/- 9 years old, 35 women) underwent echocardiographic imaging simultaneous
      with invasive measurements. An age-matched control group of 35 subjects and 60
      patients with systolic heart failure (SHF) were included for comparison. Systolic
      and diastolic dyssynchrony were assessed by tissue Doppler and defined using mean
      and SD values in the control group. RESULTS: Systolic dyssynchrony was present in
      20 patients (33%) with DHF and 24 patients (40%) with SHF and was associated in
      both groups with significantly worse left ventricular (LV) systolic and diastolic
      properties (p < 0.05 vs. control group and patients without systolic
      dyssynchrony). Diastolic dyssynchrony was present in 35 patients (58%) with DHF
      and 36 patients (60%) with SHF and had significant inverse correlations with mean
      wedge pressure and time constant of LV relaxation. In DHF patients, medical
      therapy resulted in significant shortening of diastolic time delay (39 +/- 23 ms
      to 28 +/- 20 ms; p = 0.02) but no significant change in systolic interval (p =
      0.15). Shortening of diastolic time delay correlated well with tau shortening
      after therapy (r = 0.85; p < 0.001). CONCLUSIONS: Systolic dyssynchrony occurs in
      33% of DHF patients, and diastolic dyssynchrony occurs in 58%. Medical therapy
      results in significant shortening of the diastolic intraventricular time delay
      which is closely related to improvement in LV relaxation.

PMID- 17207729
TI  - Systolic and diastolic ventricular dyssynchrony in systolic and diastolic heart
      failure.

PMID- 17207728
TI  - Diastolic and systolic asynchrony in patients with diastolic heart failure: a
      common but ignored condition.
AB  - OBJECTIVES: The present study aimed to examine whether diastolic and systolic
      asynchrony exist in diastolic heart failure (DHF) and their prevalence and
      relationship to systolic heart failure (SHF) patients. BACKGROUND: Few data exist
      on mechanical asynchrony in DHF. METHODS: Tissue Doppler echocardiography was
      performed in 373 heart failure patients (281 with SHF and 92 with DHF) and 100
      normal subjects. Diastolic and systolic asynchrony was determined by measuring
      the standard deviation of time to peak myocardial systolic (Ts-SD) and peak early
      diastolic (Te-SD) velocity using a 6-basal, 6-mid-segmental model, respectively.
      RESULTS: Both heart failure groups had prolonged Te-SD (DHF vs. SHF vs. controls
      subjects: 32.2 +/- 18.0 ms vs. 38.0 +/- 25.2 ms vs. 19.5 +/- 7.1 ms) and Ts-SD
      (31.8 +/- 17.0 ms vs. 36.7 +/- 15.2 ms vs. 17.6 +/- 7.9 ms) compared with the
      control group (all p < 0.001 vs. control subjects). Based on normal values, the
      DHF group had comparable diastolic (35.9% vs. 43.1%; chi-square = 1.48, p = NS),
      but less systolic asynchrony than the SHF group (39.1% vs. 56.9%; chi-square =
      8.82, p = 0.003). Normal synchrony, isolated systolic, isolated diastolic, and
      combined asynchrony were observed in 39.1%, 25.0%, 21.7%, and 14.1% of DHF
      patients, respectively, and these were 25.6%, 31.3%, 17.4%, and 25.6%,
      correspondingly, in SHF (chi-square = 10.01, p = 0.019). The correlation between
      systolic and diastolic asynchrony, and between the myocardial velocities and
      corresponding mechanical asynchrony appeared weak. A wide QRS duration (>120 ms)
      was rare in DHF (10.9% vs. 37.7% in SHF) (chi-square = 16.69, p < 0.001).
      CONCLUSIONS: Diastolic and/or systolic asynchrony was common in 61% of DHF
      patients despite narrow QRS complex. The presence of asynchrony was not related
      to myocardial systolic or diastolic function. Systolic and diastolic asynchrony
      were not tightly coupled, implying distinct mechanisms.

PMID- 17207730
TI  - Associations among androgens, estrogens, and natriuretic peptides in young women:
      observations from the Dallas Heart Study.
AB  - OBJECTIVES: We sought to determine if natriuretic peptides are associated with
      estrogen and androgen status in a population study of young women without known
      cardiac disease. BACKGROUND: Circulating concentrations of plasma B-type
      natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are higher in women
      than in men, and they may be influenced by estrogens and androgens. METHODS:
      Cardiac magnetic resonance imaging, dual energy X-ray absorbtiometry, and
      measurements of BNP, NT-proBNP, follicle-stimulating hormone (FSH), total
      testosterone, and sex hormone-binding globulin (SHBG), were performed in 682
      women (ages 35 to 49 years) participating in the Dallas Heart Study. RESULTS: In
      multivariable analyses adjusting for age, race/ethnicity, body mass index (BMI),
      serum creatinine, left ventricular mass and left ventricular ejection fraction
      <55%, menopausal status, and FSH were not associated with BNP and NT-proBNP. In
      contrast, higher SHBG was associated with higher BNP and NT-proBNP, while the
      free androgen index and calculated free testosterone were inversely associated
      with BNP and NT-proBNP (p < 0.0001 for each). Addition of SHBG or any measure of
      free testosterone to the multivariable models modified the effect of BMI and lean
      mass, such that measures of body composition were no longer significantly
      associated with BNP or NT-proBNP. CONCLUSIONS: Among young women, measures of
      free testosterone were independently and inversely associated with BNP and NT
      proBNP. These results suggest that circulating free testosterone, not estradiol,
      mediates gender differences in natriuretic peptides. In addition, the association
      between higher BMI and lean body mass with natriuretic peptides may be mediated
      by testosterone.

PMID- 17207731
TI  - Cardiovascular health in Europe: a global problem.

PMID- 17207732
TI  - President's page: "fix the formula" remains key issue in 2007.

PMID- 17207733
TI  - Noncardiac surgery after coronary stenting: early surgery and interruption of
      antiplatelet therapy are associated with an increase in major adverse cardiac
      events.

PMID- 17207734
TI  - Time dependence of defibrillator benefit postcoronary revascularization.

PMID- 17207736
TI  - ACCF/SCAI/SVMB/SIR/ASITN 2007 clinical expert consensus document on carotid
      stenting: a report of the American College of Cardiology Foundation Task Force on
      Clinical Expert Consensus Documents (ACCF/SCAI/SVMB/SIR/ASITN Clinical Expert
      Consensus Document Committee on Carotid Stenting).

PMID- 17207739
TI  - Sex and pain-related psychological variables are associated with thermal pain
      sensitivity for patients with chronic low back pain.
AB  - Biologic and psychological associations with evoked pain sensitivity have been
      extensively studied in healthy subjects but not among subjects with clinical pain
      syndromes. This study involved patients with chronic low back pain and
      investigated whether: 1) sex differences existed for thermal pain sensitivity;
      and 2) sex, fear-avoidance beliefs, and/or pain catastrophizing influenced
      thermal pain sensitivity. Thirty-three consecutive patients enrolled in a pain
      rehabilitation program completed self-report questionnaires and underwent
      quantitative sensory testing with an established protocol for thermal stimuli.
      Women had elevated pain sensitivity for measures of tolerance and temporal
      summation but not for first pulse response. In the multivariate models predicting
      thermal pain sensitivity, sex was associated with tolerance, and fear-avoidance
      beliefs were associated with first pulse response. Sex and pain catastrophizing
      were associated with temporal summation of thermal pain. Future studies involving
      clinical samples are necessary to replicate these findings and to explore the
      involvement of cortical structures. PERSPECTIVE: This study suggests that sex,
      fear-avoidance beliefs, and pain catastrophizing were associated with thermal
      pain sensitivity for patients with chronic low back pain. These results
      corroborated sex differences in tolerance and temporal summation observed in the
      experimental pain literature for healthy subjects. These results also suggest the
      potential for these specific pain-related beliefs to be associated with a
      sensitized state because previous studies have demonstrated their association to
      clinical pain reports, and this study demonstrated associations with thermal pain
      sensitivity.

PMID- 17207740
TI  - Is high fear of pain associated with attentional biases for pain-related or
      general threat? A categorical reanalysis.
AB  - The purpose of this investigation was to clarify mixed findings reported in
      selective attention investigations. To accomplish this, recently published dot
      probe data from 36 patients with chronic musculoskeletal pain and 29 healthy
      control participants were reanalyzed with consideration of fear of pain (FOP) as
      a categorical variable. FOP groups were identified by using a variety of
      strategies and represented differing conceptualizations of the FOP construct.
      Selective attention for sensory pain, affect pain, and health catastrophe words
      was assessed by using raw dot-probe detection latencies and the bias, congruency,
      and incongruency indices. Analysis of the raw detection latencies revealed no
      significant interactions that permit inferences regarding attentional shifts to
      or away from specific word types. Analyses of the attention indices revealed no
      evidence of pain-related selective attention as a function of FOP or the
      interaction between clinical status and FOP, regardless of the FOP categorization
      method used; however, for FOP groups derived by using the cluster method,
      participants with high FOP--all patients--exhibited hypervigilance for all word
      types on the dot-probe task when compared with those with low FOP. Implications
      for various categorical conceptualizations of FOP and future research directions
      are discussed. PERSPECTIVE: Fear of pain can be used to categorize people into
      groups more or less vulnerable to disabling effects of pain. When fear of pain
      groups are derived by using measures of general and pain-specific fearfulness,
      people with high fear of pain are likely to selectively attend all potentially
      threatening stimuli in their environment.

PMID- 17207741
TI  - Physician pain reminder as an intervention to enhance analgesia for extremity and
      clavicle injuries in pediatric emergency.
AB  - The purpose of this study was to document analgesic use for limb and clavicle
      injuries in the pediatric emergency department (ED) and to determine whether a
      physician-oriented pain scale form on the patient's chart would enhance the
      administration of analgesia. Patients 3 to 18 years old were recruited
      prospectively in our tertiary pediatric ED in Toronto. The study included 4
      crossover periods, 2 with the pain scale form on the patient's chart and 2
      without. A total of 310 patients were recruited, mean age was 10 years, 64% were
      boys, and 62% had sustained fractures. The mean pain score was 4.4. Only 90 (29%)
      patients received an analgesic in the ED, and 65 (72%) of them were ordered by a
      physician. Only 24 (20%) in the study group and 22 (14%) in the control group
      received sufficient analgesia (P = .13). The median time to physician-initiated
      analgesia after arrival was 2.0 hours (1.0 to 3.3 hours), without a significant
      difference between groups. Pain control was 4-fold more appropriate in children
      receiving opioids versus nonopioids. Physician pain reminders did not enhance,
      and other measures should be taken to increase the dispensing of analgesia.
      PERSPECTIVE: This is the first study to evaluate whether the addition of a
      physician-oriented pain-scale form on the chart of patients with injuries
      improves administration of analgesia in the ED. We found that physicians do not
      give sufficient analgesia even with this reminder form.

PMID- 17207742
TI  - Subarachnoid transplant of a human neuronal cell line attenuates chronic
      allodynia and hyperalgesia after excitotoxic spinal cord injury in the rat.
AB  - The relief of neuropathic pain after spinal cord injury (SCI) remains daunting,
      because pharmacologic intervention works incompletely and is accompanied by
      multiple side effects. Transplantation of human cells that make specific biologic
      agents that can potentially modulate the sensory responses that are painful would
      be very useful to treat problems such as pain. To address this need for
      clinically useful human cells, the human neuronal NT2 cell line was used as a
      source to isolate a unique human neuronal cell line that synthesizes and
      secretes/releases the inhibitory neurotransmitters gamma-aminobutyric acid (GABA)
      and glycine. This new cell line, hNT2.17, expresses an exclusively neuronal
      phenotype, does not incorporate bromodeoxyuridine during differentiation, and
      does not express the tumor-related proteins fibroblast growth factor 4 and
      transforming growth factor-alpha during differentiation after 2 weeks of
      treatment with retinoic acid and mitotic inhibitors. The transplant of
      predifferentiated hNT2.17 cells was used in the excitotoxic SCI pain model, after
      intraspinal injection of the mixed AMPA/metabotropic receptor agonist quisqualic
      acid (QUIS). When hNT2.17 cells were transplanted into the lumbar subarachnoid
      space, tactile allodynia and thermal hyperalgesia induced by the injury were
      quickly and potently reversed. Control cell transplants of nonviable hNT2.17
      cells had no effect on the hypersensitivity induced by QUIS. The effects of
      hNT2.17 cell grafts appeared 1 week after transplants and did not diminish during
      the 8-week course of the experiment when grafts were placed 2 weeks after SCI.
      Immunohistochemistry and quantification of the human grafts were used to ensure
      that many grafted cells were still present and synthesizing GABA at the end of
      the study. These data suggest that the human neuronal hNT2.17 cells can be used
      as a "biologic minipump" for antinociception in models of SCI and neuropathic
      pain. PERSPECTIVE: This study describes the initial characterization and use of a
      human-derived cell line to treat neuropathic pain that would be suitable for
      clinical application, once further tested for safety and approved by the Food and
      Drug Administration. A dose of these human cells could be delivered with a spinal
      tap and affect the intrathecal spinal environment for sensory system modulation.

PMID- 17207744
TI  - Midwifery and gender equality.

PMID- 17207743
TI  - A comparison of different severities of nausea and vomiting during pregnancy
      relative to stress, social support, and maternal adaptation.
AB  - A cross-sectional and comparative research design with convenience sampling was
      used to recruit pregnant women from prenatal clinics in southern Taiwan between
      2002 and 2003 to examine the differences in perceived stress, social support, and
      maternal psychosocial adaptation among women with different severities (mild or
      less than mild, moderate, and severe) of nausea and vomiting during pregnancy. A
      total of 150 pregnant women participated in this study. One-way analysis of
      variance indicated that perceived stress was significantly different among the 3
      groups. The least significant difference post-hoc test revealed that pregnant
      women with mild nausea and vomiting had significantly lower stress than did
      pregnant women with severe nausea and vomiting. The severity of nausea and
      vomiting was significantly associated with the Prenatal Self Evaluation
      Questionnaire subscales for "acceptance of pregnancy" and "fear of helplessness
      and loss of control in labor." Social support and maternal psychosocial
      adaptation were not significantly different among these three groups. The degree
      of perceived stress and maternal psychosocial adaptation may be related to the
      severity of nausea and vomiting during pregnancy.

PMID- 17207745
TI  - Collaborative management of women with bipolar disorder during pregnancy and
      postpartum: pharmacologic considerations.
AB  - Bipolar disorder is a chronic condition characterized by periods of mania,
      depression, or mixed states (co-occurring mania and depression). The postpartum
      period is associated with a high risk for symptom relapse or intensification,
      which can be reduced with the use of medications. Abrupt discontinuation of these
      medications increases the probability of relapse, which is associated with high
      risk behaviors, significant family dysfunction, and suicide. Drugs used to treat
      patients with bipolar disorder vary in teratogenic potential. Although first
      trimester lithium use is associated with Ebstein's anomaly, the risk was
      overestimated in the past. Valproate and its derivatives and carbamazepine are
      human teratogens. Lamotrigine does not negatively impact major reproductive
      outcomes, but the data are limited. Typical antipsychotic medications are
      relatively well studied and the data do not identify major morphologic
      teratogenicity. There are fewer studies of newer atypical antipsychotic
      medications, and registries have been developed to collect prospective data.
      Clinical management of bipolar disorder during pregnancy, postpartum, and
      lactation requires a careful balancing of maternal and fetal risks and benefits.
      Communication and careful comanagement between the obstetric and psychiatric team
      is essential when treating women with bipolar disorder during the reproductive
      years.

PMID- 17207746
TI  - The DNP and entry into midwifery practice: an analysis.
AB  - The American Association of Colleges of Nursing recently published a policy
      statement calling for the requirement of the Doctor of Nursing Practice for entry
      into practice as an Advanced Practice Nurse by the year 2015. Certified nurse
      midwives, defined as those educated in both nursing and midwifery, are commonly
      included in the definition of Advanced Practice Nurses, along with nurse
      practitioners, nurse anesthetists, and clinical nurse specialists. This paper
      explores issues related to the practice doctorate as an entry requirement for
      midwifery practice in the United States. The results of a brief survey of
      midwifery students indicate mixed interest in a clinical doctorate. At the
      present time, evidence points to the fact that current education requirements
      produce safe, knowledgeable, competent midwives. Because data are lacking
      regarding the potential impact of the proposed Doctor of Nursing Practice on the
      cost of education to both the institution and the student, on the applicant pool,
      and on the health care system, the Directors of Midwifery Education endorse a
      statement affirming support for multiple routes of midwifery education based on
      the ACNM Core Competencies, and does not endorse a mandatory requirement for the
      clinical doctorate for entry into practice at this time.

PMID- 17207747
TI  - Update on medication abortion.
AB  - This article provides an overview of medication abortion in the United States 6
      years after the approval of mifepristone (RU486; Mifeprex; Danco Laboratories,
      LLC, New York, NY) by the US Food and Drug Administration (FDA). The adoption of
      mifepristone is considered in the context of epidemiologic data on abortion,
      abortion access, and the safety of abortion. The risks of medication and
      aspiration abortion are discussed in the context of abortion-related mortality,
      recent experience with obstetric and gynecologic infection with Clostridium
      sordellii, and the limits of scientific knowledge on the incidence of this
      infection in women. Innovative protocols studied since FDA approval of
      mifepristone are presented, and implications for clinical practice are discussed.

PMID- 17207748
TI  - Does epidural analgesia affect the rate of spontaneous obstetric lacerations in
      normal births?
AB  - The precise relationship between epidural use and genital tract lacerations in
      normal childbirth is unclear. Data from a clinical trial on measures to lower
      genital tract trauma in vaginal birth were used for a secondary analysis. The
      goal was to assess whether epidurals affect the rate of spontaneous obstetric
      lacerations in normal vaginal births. Maternal characteristics and intrapartum
      variables were compared in women who did and did not use an epidural in labor,
      and also in those with and without any sutured lacerations following vaginal
      birth. Variables that were statistically different in both cases were entered
      into regression equations for simultaneous adjustment. Epidural use was not an
      independent predictor of sutured lacerations. Predictors of sutured lacerations
      included nulliparity, a prolonged second stage, being non-Hispanic white, and an
      infant birthweight greater than 4000 grams. Elements of midwifery management need
      further research.

PMID- 17207749
TI  - Use of a clean delivery kit and factors associated with cord infection and
      puerperal sepsis in Mwanza, Tanzania.
AB  - Our objective was to determine the effectiveness of an intervention that
      incorporated education about the "six cleans" with the use of a clean delivery
      kit in preventing cord infection and puerperal sepsis. A stepped-wedge, cross
      sectional study was conducted in 10 surveillance sites across two rural districts
      of Mwanza Region, Tanzania. A total of 3262 pregnant women between the ages of 17
      and 45 years were enrolled in the study. Village health workers administered
      questionnaires to each mother at 5 days postpartum and inspected the infants'
      umbilical cord stumps for signs of infection. Newborns whose mothers used the
      delivery kit were 13.1 times less likely to develop cord infection than infants
      whose mothers did not use the kit. Furthermore, women who used the kit for
      delivery were 3.2 times less likely to develop puerperal sepsis than women who
      did not use the kit. Women who bathed before delivery were 2.6 times less likely
      to develop puerperal sepsis than women who did not bathe, and their infants were
      3.9 times less likely to develop cord infection. Single-use delivery kits, when
      combined with education about clean delivery, can have a positive impact on the
      health of women and their newborns by significantly decreasing the likelihood of
      developing puerperal sepsis or cord infection.

PMID- 17207750
TI  - Pruritic urticarial papules and plaques of pregnancy.
AB  - Pruritic urticarial papules and plaques of pregnancy (PUPPP) are among the most
      common pruritic dermatoses observed in pregnant women. PUPPP appears most
      frequently in the third trimester, in primigravidas, and in multiple gestation
      pregnancies. The eruption of changes occurs initially on the abdomen and extends
      over the thighs, legs, back, buttocks, arms, and breasts. Skin changes typical
      for PUPPP are erythematous, urticarial plaques, and papules. Rash regression is
      usually observed within 6 weeks postpartum. Immunologic mechanisms, hormonal
      abnormalities, and abdominal skin distension have been suggested as etiologic
      mechanisms. PUPPP is thought to be harmless for the mother and fetus and usually
      requires intervention only for symptom relief. In some cases, laboratory
      investigation, histologic examination, and immunologic study should be performed
      to exclude more serious disorders of pregnancy, such as herpes gestationis or
      intrahepatic cholestasis of pregnancy. This article reviews the epidemiology,
      clinical manifestation, etiology, differential diagnosis, and treatment of PUPPP.

PMID- 17207751
TI  - Midwives and the fetal nuchal cord: a survey of practices and perceptions.
AB  - A systematic search of studies of intrapartum management of the nuchal umbilical
      cord at term found no published controlled studies in this area. A postal survey
      containing both structured and open questions and a request for local protocols
      and guidelines was sent to all 637 midwives in 7 maternity units in England.
      There were 401 (63%) responses. There appeared to be no unit guidelines for this
      area of practice. Midwife approaches to nuchal cord during birth varied, and
      included clamping and cutting of loose nuchal cords and a hands-off approach to
      tight nuchal cords. Reasons for specific actions included doing what had been
      taught during midwifery training and learning from previous personal experiences.
      Theories of diffusion of innovation and of planned behaviour may provide a
      conceptual basis for understanding the adoption of specific practices. Future
      qualitative and controlled studies are needed to explore the nature and
      consequences of varying approaches to intrapartum nuchal cord management.

PMID- 17207753
TI  - Midwifery models: students' conceptualization of a midwifery philosophy in clay.
AB  - Formulating a professional and personal philosophy statement assists nurses and
      midwives in clarifying focus and direction. It also facilitates grounding of the
      nursing and midwifery professions or professionals by enabling the identification
      of both shared beliefs and unique elements. The purpose of this activity was to
      assist beginning student nurse-midwives (SNMs) in exploring the intersection of
      their own and the profession's philosophy. Through the creation of a clay
      representation of their philosophical model, eight SNMs expressed their midwifery
      philosophies at the beginning of their clinical sequence by sculpting them in
      clay and then described their sculptures and how they exemplified their
      philosophies.

PMID- 17207752
TI  - The role of exercise in treating postpartum depression: a review of the
      literature.
AB  - There is now evidence to support the antidepressant effects of exercise in
      general and in clinical populations. This article reviews the evidence regarding
      the potential role of exercise, particularly pram walking, as an adjunctive
      treatment for postpartum depression. Database searches revealed two small
      randomised controlled trials conducted in Australia which support exercise as a
      useful treatment for women with postpartum depression. In addition, uncontrolled
      studies and observational evidence suggest that postpartum women, some of whom
      were depressed, report benefit from participation in exercise programmes. There
      are plausible mechanisms by which exercise could have such an effect. Limited
      evidence supports a relationship between participation in exercise and reduction
      in postpartum depression. Given the reluctance by some women to use
      antidepressant medication postpartum and the limited availability of
      psychological therapies, exercise as a therapeutic possibility deserves further
      exploration. Further research using well-designed randomised controlled trial
      methodologies are warranted.

PMID- 17207754
TI  - Management of intrahepatic cholestasis of pregnancy: a case report.

PMID- 17207755
TI  - Oligohydramnios at term: a case report.

PMID- 17207758
TI  - Trends in CNM-attended births, 1990-2004.

PMID- 17207759
TI  - Placentas in the fridge--on being the daughter of a midwife.

PMID- 17207760
TI  - Clinical presentation and treatment outcome of sleeping sickness in Sudanese pre
      school children.
AB  - BACKGROUND: Existing data on human African trypanosomiasis (HAT) due to
      Trypanosoma brucei gambiense among children are limited. Here, we described the
      demographic, clinical, diagnostic, treatment and outcome characteristics of HAT
      in pre-school children from Kajo-Keji County, South Sudan in comparison with
      older patients. METHODS: We did a retrospective analysis of HAT patients treated
      at the Kiri Sleeping Sickness Treatment Centre (SSTC), Kajo-Keji County, from
      June 2000 to December 2002. RESULTS: Of 1958 HAT patients, 119 (6.1%) were pre
      school children (<6 years) including 56 (47%) in first-stage illness and 63 (53%)
      in second-stage. The proportion of children in second-stage HAT was significantly
      higher in very young children (<2 years). Walking and speech disturbances were
      more frequent in second-stage HAT but other neurological symptoms and signs were
      not associated with disease stage. Pentamidine treatment for first-stage illness
      was very safe and effective among pre-school children. In contrast, 4.9% of pre
      school children in second-stage illness died during melarsoprol treatment and 46%
      had > or = 1 severe adverse event(s). Macular rash, jaundice and skin necrosis on
      injection site were significantly more frequent in this age group (p<0.05).
      Melarsoprol-induced encephalopatic syndrome was less frequent but more severe
      than in older age groups. CONCLUSION: The clinical features of T. b. gambiense
      HAT among pre-school children are insufficiently stage-specific. Therefore,
      laboratory-based staging is mandatory to prevent unnecessary harm to HAT patients
      caused by the high toxicity of melarsoprol.

PMID- 17207761
TI  - The Calcineurin A homologue from Trypanosoma cruzi lacks two important regulatory
      domains.
AB  - A novel protein from the parasite Trypanosoma cruzi homologous to calcineurin
      (serine-threonine phosphatase 2B) was identified and characterized. The
      Calcineurin A gene is present as a single copy gene per haploid genome and
      encodes a protein of 43 kDa that is expressed in all major developmental stages
      of T. cruzi. Surprisingly, it is mainly localized in the cell nucleus, in sharp
      contrast with its mammalian counterpart. The T. cruzi calcineurin A protein
      presents the three invariants motifs characteristic of the PPP serine-threonine
      phosphatase superfamily. However, out of the four domains typically present in
      all calcineurin described to date, the T. cruzi calcineurin A possess only two
      domains: the catalytic and the calcineurin B binding domain. Sequence similarity
      searches in the T. cruzi, Trypanosoma brucei and Leishmania major genomes
      revealed that only L. major presents a gene encoding a putative protein
      containing the four domains. On the other hand, the T. cruzi Calcineurin B
      subunit showed a conserved structure, and a reasonable level of similarity over
      the entire length with calcineurin B proteins from other organisms. Interaction
      between Calcineurin A and Calcineurin B was analyzed by yeast Two-Hybrid and GST
      pull-down assays.

PMID- 17207762
TI  - Disjoining pressure of thin films stabilized by nonionic surfactants.
AB  - In this article an attempt is made to derive a comprehensive theory of the
      disjoining pressure of thin liquid films, stabilized by low molecular nonionic
      surfactants. We accounted for effects playing a role in the case of surfactants
      with spherical hydrophilic heads: (i) The thermal fluctuations of the adsorbed
      surfactant molecules, due to the fact that the energy of adsorption of a -CH(2)-
      group is approximately equal to the average thermal energy k(B)T; (ii) The
      contribution of the collisions between molecules adsorbed on different surfaces;
      (iii) The restriction imposed on the fluctuation of the molecules by the presence
      of a second surface situated at a small distance h from the interface where the
      molecules are adsorbed; (iv) The volume of the hydrophilic heads, which expels
      part of the water molecules from the film region; (v) The equilibrium between the
      molecules adsorbed at the film surfaces and at the menisci surrounding the film.
      The adsorption on the film surfaces has two main effects. First, the
      concentration of solute inside the film region becomes larger than in the bulk
      solution and this will push the solvent toward the film thus creating an osmotic
      pressure (the disjoining pressure), which tends to increase the film thickness.
      Second, the higher concentration inside the film and the collisions between the
      polar heads lead to higher chemical potential, which pushes the surfactant toward
      the meniscus. We treated these effects by modifying adequately the Hildebrand
      Scatchard theory for the osmotic pressure of concentrated solutions. The
      partition function of the surfactant, needed for this calculation, was found by
      deriving an expression for the configurational integral, based on virial
      expansion. The surface equations of state of Helfand, Frisch and Lebowitz and
      Volmer were critically analyzed and then generalized, by using the partition
      function obtained by virial expansion, to permit the derivation of partition
      functions of the surfactant molecules in the film. A simple thermodynamic
      approach was developed and applied to derive expressions for the disjoining
      pressure, Pi, and the chemical potential of the surfactant molecules in the film,
      mu. They were used to calculate numerically Pi and mu and analyze their
      dependence on the film thickness h and the surface coverage theta. It turned out
      that Pi has completely different behavior above and below h=2d, where d is the
      diameter of the hydrophilic head. For thick films, with h>2d, the decay of Pi is
      initially exponential (due mainly to the thermal fluctuations of the adsorbed
      molecules), followed by a long tail, proportional to h(-2), due to the
      contribution of the osmotic pressure of the displaced solvent molecules. At h<2d
      the collisions between the molecules adsorbed at different surfaces are hindered,
      which leads to a steady decrease of the contribution due the interaction between
      the molecules. The overall result of these effects is the appearance of a maximum
      of Pi at h=2d. It is very large (it may reach 1000 atm and even more) and depends
      strongly on the surfactant adsorption. To facilitate the application and the
      analysis of the theory, we derived several simpler asymptotic expressions. One of
      them is virial expansion, which is valid for small surface coverage and has the
      advantage of being independent of the adsorption model. The other asymptotic
      expression is applicable at h>2d, which is the region where the stabilization of
      the film occurs. We compared our theory with the simpler theory of Israelachvili
      and Wennerstrom. It turned out that while both theories lead to decay of Pi vs.
      h, the numerical results and the shape of the curves are usually very different.
      The experimental data, which could be used to verify our theory, are scarce, but
      we found reasonable agreement with the data of Lyle and Tiddy for bilayers of
      C(12)EO(4). The data of Parsegian et al. for lipid bilayers also confirmed
      qualitatively some of our theoretical conclusions.

PMID- 17207763
TI  - Occurrence of N-acyl-L-homoserine lactones in extracts of some Gram-negative
      bacteria evaluated by gas chromatography-mass spectrometry.
AB  - Acylated homoserine lactones (AHLs) are self-generated signal molecules that
      mediate population density-dependent gene expression (quorum sensing) in a
      variety of Gram-negative bacteria. These signal molecules diffuse from bacterial
      cells and accumulate in the medium as a function of cell growth. In selected
      foods AHLs contribute to product spoilage. As different bacterial species produce
      AHL analogs that differ in length of the N-acyl chain, ranging from 4 to 14
      carbons and in the substitution at the C-3 position of the side chain (i.e., oxo
      or hydroxyl group), the suitability and applicability of a gas chromatography
      mass spectrometry direct method for characterizing trace amounts of AHLs was
      evaluated using N-heptanoyl-homoserine lactone as internal standard. Crude cell
      free supernatants of bacterial cultures of Aeromonas hydrophila, Aeromonas
      salmonicida, Pseudomonas aeruginosa, Pseudomonas fluorescens, Yersinia
      enterocolitica, and Serratia liquefaciens were screened for AHL production in
      selected ion monitoring mode, using the prominent fragment at m/z 143. The
      observed profiles of distinguishable N-acyl-homoserine lactones occurring in
      bacterial extracts were compared and discussed. The presence of a labile 3-oxo
      hexanoylhomoserine lactone was evidenced but serious difficulties arose in
      estimating its concentration as thermal degradation occurs during the gas
      chromatographic separation. Its electron impact mass spectra was, however, given
      and interpreted.

PMID- 17207764
TI  - Kinetic modeling and fitting software for interconnected reaction schemes:
      VisKin.
AB  - Reaction kinetics for complex, highly interconnected kinetic schemes are modeled
      using analytical solutions to a system of ordinary differential equations. The
      algorithm employs standard linear algebra methods that are implemented using
      MatLab functions in a Visual Basic interface. A graphical user interface for
      simple entry of reaction schemes facilitates comparison of a variety of reaction
      schemes. To ensure microscopic balance, graph theory algorithms are used to
      determine violations of thermodynamic cycle constraints. Analytical solutions
      based on linear differential equations result in fast comparisons of first order
      kinetic rates and amplitudes as a function of changing ligand concentrations. For
      analysis of higher order kinetics, we also implemented a solution using numerical
      integration. To determine rate constants from experimental data, fitting
      algorithms that adjust rate constants to fit the model to imported data were
      implemented using the Levenberg-Marquardt algorithm or using Broyden-Fletcher
      Goldfarb-Shanno methods. We have included the ability to carry out global fitting
      of data sets obtained at varying ligand concentrations. These tools are combined
      in a single package, which we have dubbed VisKin, to guide and analyze kinetic
      experiments. The software is available online for use on PCs.

PMID- 17207765
TI  - Use of a cyanine dye as a probe for albumin and collagen in the extracellular
      matrix.
AB  - The aim of this work was to develop a quick method for analysis of macromolecules
      of the extracellular matrix. Of great interest are soluble components of the
      extracellular matrix, in particular, carrier proteins, whose variation dynamics
      can characterize the studied tissue in its development, adult stage, and aging.
      We suggest the method of analysis of the extracellular matrix to reveal the
      presence of albumin and collagen by using an anionic cyanine dye as a spectral
      and fluorescence probe. The method was applied for the analysis of the human
      vitreous body in the course of its development. Albumin was detected by the
      appearance of the trans monomer absorption and fluorescence bands in the dye
      spectra, and collagen was detected by the absorption and fluorescence bands of J
      aggregates. Hyaluronic acid present in the vitreous body does not interfere with
      the results of the analysis. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and Western blot analysis confirmed the presence of albumin in
      the vitreous body. We suppose that albumin as a protein carrying biologically
      active macromolecules plays an important role in the processes of differentiation
      and functional establishment of ocular tissues in the course of their prenatal
      development.

PMID- 17207767
TI  - VDAC1 serves as a mitochondrial binding site for hexokinase in oxidative muscles.
AB  - Voltage-dependent anion channels (VDACs), also known as mitochondrial porins, are
      the main pathway for metabolites across the mitochondrial outer membrane and may
      serve as binding sites for kinases, including hexokinase. We determined that
      mitochondria-bound hexokinase activity is significantly reduced in oxidative
      muscles (heart and soleus) in vdac1(-/-) mice. The activity data were supported
      by western blot analysis using HK2 specific antibody. To gain more insight into
      the physiologic mean of the results with the activity data, VDAC deficient mice
      were subjected to glucose tolerance testing and exercise-induced stress, each of
      which involves tissue glucose uptake via different mechanisms. vdac1(-/-) mice
      exhibit impaired glucose tolerance whereas vdac3(-/-) mice have normal glucose
      tolerance and exercise capacity. Mice lacking both VDAC1 and VDAC3 (vdac1(-/
      )/vdac3(-/-)) have reduced exercise capacity together with impaired glucose
      tolerance. Therefore, we demonstrated a link between VDAC1 mediated mitochondria
      bound hexokinase activity and the capacity for glucose clearance.

PMID- 17207766
TI  - Hybrid homology modeling and mutational analysis of cytochrome P450C24A1
      (CYP24A1) of the Vitamin D pathway: insights into substrate specificity and
      membrane bound structure-function.
AB  - Cytochrome P450C24A1 (CYP24A1), a peripheral inner mitochondrial membrane
      hemoprotein and candidate oncogene, regulates the side-chain metabolism and
      biological function of vitamin D and many of its related analog drugs. Rational
      mutational analysis of rat CYP24A1 based on hybrid (2C5/BM-3) homology modeling
      and affinity labeling studies clarified the role of key domains (N-terminus, A',
      A, and F-helices, beta3a strand, and beta5 hairpin) in substrate binding and
      catalysis. The scope of our study was limited by an inability to purify stable
      mutant enzyme targeting soluble domains (B', G, and I-helices) and suggested
      greater conformational flexibility among CYP24A1's membrane-associated domains.
      The most notable mutants developed by modeling were V391T and I500A, which
      displayed defective-binding function and profound metabolic defects for 25
      hydroxylated vitamin D3 substrates similar to a non-functional F-helix mutant
      (F249T) that we previously reported. Val-391 (beta3a strand) and Ile-500 (beta5
      hairpin) are modeled to interact with Phe-249 (F-helix) in a hydrophobic cluster
      that directs substrate-binding events through interactions with the vitamin D cis
      triene moiety. Prior affinity labeling studies identified an amino-terminal
      residue (Ser-57) as a putative active-site residue that interacts with the 3beta
      OH group of the vitamin D A-ring. Studies with 3-epi and 3-deoxy-1,25(OH)2D3
      analogs confirmed interactions between the 3beta-OH group and Ser-57 effect
      substrate recognition and trafficking while establishing that the trans
      conformation of A-ring hydroxyl groups (1alpha and 3beta) is obligate for high
      affinity binding to rat CYP24A1. Our work suggests that CYP24A1's amphipathic
      nature allows for monotopic membrane insertion, whereby a pw2d-like substrate
      access channel is formed to shuttle secosteroid substrate from the membrane to
      the active-site. We hypothesize that CYP24A1 has evolved a unique amino-terminal
      membrane-binding motif that contributes to substrate specificity and docking
      through coordinated interactions with the vitamin D A-ring.

PMID- 17207768
TI  - Cognitive development and the interpretation of anxiety-related physical symptoms
      in 4-13-year-old non-clinical children.
AB  - The present study examined developmental patterns in children's interpretation of
      anxiety-related physical symptoms and emotional reasoning (i.e., the tendency to
      infer danger on the basis of physical response information). A sample of 171
      children aged between 4 and 13 years were interviewed after listening to a number
      of vignettes in which the presence and absence of physical symptoms was
      systematically varied. Results revealed the expected developmental pattern for
      anxiety-related interpretations of physical symptoms. More precisely, from age 7,
      children were increasingly capable of linking physical symptoms to the emotion of
      anxiety. Furthermore, support was obtained for an emotional reasoning effect.
      That is, children rated vignettes with physical symptoms as more dangerous than
      vignettes without such symptoms. While the emotional reasoning effect was present
      in children of all ages, this phenomenon was more salient among older children.
      Finally, cognitive development as measured by Piagetian conservation tasks
      appeared to influence children's anxiety-related interpretations of physical
      symptoms and emotional reasoning. Altogether, these findings are relevant for
      researchers who are interested in "physical symptoms-based" theories of childhood
      anxiety.

PMID- 17207769
TI  - Emotion regulation and trichotillomania: a comparison of clinical and nonclinical
      hair pulling.
AB  - This study investigated the emotion regulation hypothesis of trichotillomania
      (TTM) using a retrospective self-report measure and an experimental hair-pulling
      task. Participants diagnosed with TTM (n=34) and nonclinical control (NC)
      volunteers (n=32) were compared on ratings of emotional experiences associated
      with hair pulling. Data from the retrospective self-report measure supported the
      emotion regulation hypothesis of TTM. The TTM group reported larger decreases
      than the NC participants in boredom, sadness, anger, and tension, and larger
      increases in relief and calm from before to during pulling. The TTM group also
      reported significantly higher ratings of pleasure while pulling. When exploring
      changes in emotions from during to after pulling, the TTM group reported larger
      increases than the NC participants in guilt, sadness, and anger; and larger
      decreases in boredom; while the NC group reported larger increases than the TTM
      group in happiness, calm, and relief. On the experimental hair-pulling task, the
      TTM group reported larger decreases in anxiety from before to after pulling, but
      this effect was only found for a nontypical hair-pulling site. Methodological
      limitations may account for the lack of group differences on the experimental
      hair-pulling task.

PMID- 17207770
TI  - Transcriptional downregulation of sterol metabolism genes in murine liver exposed
      to acute hypobaric hypoxia.
AB  - Ascent to high-altitude results in decreased inspired partial pressure of oxygen
      because of a decrease in barometric pressure. Altitude acclimatization requires
      physiological and metabolic changes to improve tolerance to altitude hypoxia.
      Cellular response to hypoxia results into changes in the profile of gene
      expression and the present study explored the same in murine model. Liver being
      the largest metabolic organ, the molecular details of acute hypobaric hypoxia
      (AHH) induced transcriptional changes in the tissue were investigated. Swiss
      albino mice were exposed to hypobaric hypoxia ( approximately 426mmHg) in a
      decompression chamber and cDNA microarray was used to study the transcriptional
      profile in liver. Notably, by the tenth hour several of the genes involved in
      sterol metabolism such as SREBF1, INSIG1, HMGCS1, FDFT1, SQLE, and HSD3B4 were
      downregulated more than 2-fold suggesting that AHH suppresses sterol biosynthesis
      in the liver. Real-time PCR helped validate the downregulation of SREBF1, HMGCS1,
      FDFT1, and HSD3B4 genes. However, no significant change was observed in the serum
      cholesterol levels throughout the AHH exposure. The findings are indicative of
      transcriptional downregulation of SREBP target genes as a part of acclimatization
      response to hypoxia. The study highlights the significance of SREBP in the
      regulation of sterol metabolism under the acute hypoxic response.

PMID- 17207771
TI  - Resistin induces insulin resistance in pancreatic islets to impair glucose
      induced insulin release.
AB  - An adipokine resistin, a small cysteine-rich protein, is one of the major risk
      factors of insulin resistance. In the present study, transiently resistin
      expressing mice using adenovirus method showed an impaired glucose tolerance due
      to insulin resistance. We found that resistin-expressing mice exhibited impaired
      insulin secretory response to glucose. In addition, in vitro treatment with
      resistin for 1 day induced insulin resistance in pancreatic islets and impaired
      glucose-stimulated insulin secretion by elevating insulin release at basal
      glucose (2.8 mM) and suppressing insulin release at stimulatory glucose (8.3 mM).
      In addition, resistin inhibited insulin-induced phosphorylation of Akt in islets
      as well as other insulin target organs. Furthermore, resistin induced SOCS-3
      expression in beta-cells. In conclusion, resistin induces insulin resistance in
      islet beta-cells at least partly via induction of SOCS-3 expression and reduction
      of Akt phosphorylation and impairs glucose-induced insulin secretion.

PMID- 17207772
TI  - Characterization of the ColE2-like replicon of plasmid pTT8 from Thermus
      thermophilus.
AB  - We identified the 1.6-kb region of Thermus thermophilus plasmid pTT8 capable of
      autonomous replication, which shows a significant sequence similarity to the
      replicon regions of the ColE2-related plasmids. We showed the requirement of DNA
      polymerase I for pTT8 replication. The putative rep gene coding for the
      replication initiator protein, Rep, similar to those of the ColE2-related
      plasmids was cloned into an expression vector. The 6xHis-Rep protein expressed in
      Escherichia coli was successfully purified by stepwise denaturing with urea and
      refolding in the presence of glycerol on Ni-resin. We identified the nucleotide
      sequence recognized by the pTT8 Rep protein by the SELEX experiment using the
      purified protein, and proposed the existence of the third origin of pTT8
      replication different from those predicted previously.

PMID- 17207773
TI  - Telomerase activation induces elongation of the telomeric single-stranded
      overhang, but does not prevent chromosome aberrations in human vascular
      endothelial cells.
AB  - Chromosome aberrations such as loss of chromosome 13 were frequently observed in
      human endothelial cells from umbilical cord veins (HUVEC). A recent study showed
      that the length of telomeric single-stranded 3'-overhangs (G-tails) is more
      important as an essential structure for chromosome maintenance than the net
      telomere length in telomere t-loop formation. Here, we have examined G-tail
      length using G-tail telomere HPA in normal and hTERT-transduced HUVECs. We found
      that forced expression of hTERT in HUVEC induced G-tail as well as total telomere
      length elongation. G-tail length was well correlated with total telomere length.
      However, hTERT introduction did not prevent chromosome aberrations such as loss
      of chromosome 13. Normal characteristics such as morphology, up-regulation of
      vWF, and tube formation were observed in hTERT-HUVEC as in young normal HUVEC.
      These results show that chromosome aberrations in HUVEC are independent of
      telomere G-tail and total telomere attrition.

PMID- 17207774
TI  - Processing of nerve growth factor: the role of basic amino acid clusters in the
      pro-region.
AB  - Neurotrophins are synthesized first as precursors called pro-neurotrophins, and
      their propeptides are then proteolytically removed to form mature neurotrophins.
      However, a significant proportion of total neurotrophins has been shown to be
      secreted as pro-neurotrophins. Furthermore, pro- and mature neurotrophins have
      been shown to elicit opposite effects on cell survival. Thus, the processing step
      of neurotrophins is very important. In order to understand the mechanism of
      neurotrophin processing, we focused on the two basic amino acid clusters in the
      pro-region of nerve growth factor (NGF). Various NGFs mutated at basic amino
      acids in the pro-region were introduced in COS7 and PC12 cells. The results
      indicated that these basic amino acid clusters were actually cleaved in the cells
      by furin, but that their cleavage contributed little to the production of mature
      NGF. However, one of the two sites was considered to contribute to mature NGF
      production depending on conditions used.

PMID- 17207775
TI  - Reactive oxygen species generation through NADH oxidation by 6-formylpterin
      derivatives in the dark.
AB  - 6-formylpterin (6FP) has been reported to produce reactive oxygen species (ROS)
      such as *O2- and H2O2 from O2 in the presence of NADH under light condition. In
      the present study, we prepared a variety of 6FP derivatives and found that 2-(N,N
      dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridin-4-one and 2-(N,N
      dimethylaminomethyleneamino)-6-formyl-3-methylpteridin-4-one, in which the 2
      amino groups are modified by a dimethylaminomethylene group and the 3-positions
      by pivaloyl and methyl groups and 2-amino-6-formyl-3-methylpteridin-4-one in
      which the amino group at the 2-position is free and the 3-position is modified by
      a methyl group generated H2O2 from O2 on oxidation of NADH to NAD+ in the dark.
      However, 6FP and 2-(N,N-dimethylaminomethyleneamino)-6-formylpteridin-4-one, in
      which the 3-position is free did not yield H2O2. These results indicate that
      modification of the 3-position is essential to make the activities of 6FP
      available in the dark and would be suggestive for designing pharmaceutical
      compounds that generate appropriate and controllable amounts of ROS in vivo.

PMID- 17207776
TI  - Relationship between mRNA stability and intron presence.
AB  - Introns were found to enhance almost every steps of gene expression except
      increasing mRNA stability. By analyzing the genome-wide data of mRNA stability
      published by someone previously, we found that human intron-containing genes have
      more stable mRNAs than intronless genes, and the Arabidopsis thaliana genes with
      the most unstable mRNAs have fewer introns than other genes in the genome. After
      controlling for mRNA length, we found mRNA stability is still positively
      correlated with intron number in human intron-containing genes. But in yeast
      Saccharomyces cerevisiae, two different datasets on mRNA half-life gave
      conflicting results. The components of messenger ribonucleoprotein particles
      recruited during intron splicing may be retained in cytoplasmic mRNPs and act as
      signals of mRNA stability or simply insulators to avoid mRNA degradation.

PMID- 17207777
TI  - Revisiting the backward masking deficit in schizophrenia: individual differences
      in performance and modeling with transcranial magnetic stimulation.
AB  - BACKGROUND: Deficits in backward masking have been variably reported in
      schizophrenia patients, but individual differences in the expression of these
      deficits have not been explicitly investigated. In addition, increased knowledge
      of the visual system has opened the door for new techniques such as transcranial
      magnetic stimulation (TMS) to explore these deficits physiologically. METHODS:
      Patients with schizophrenia and healthy controls were tested using a backward
      masking paradigm. In order to examine the functionality of visual pathways
      involved in backward masking, subjects were retested on a backward masking
      paradigm using single pulse TMS applied to occipital cortex in lieu of the
      masking stimuli. RESULTS: Compared with controls, patients had significantly
      delayed recovery from visual backward masking. However, 23.5% of patients
      (compared to 5% of controls) never recovered to levels approaching unmasked
      performance. When these subjects were segregated from the analysis, group
      differences vanished. In addition, stimulus masking with occipital TMS followed
      the same pattern in both patients and controls. CONCLUSIONS: Observations of
      individual differences in visual masking performance may identify a subgroup of
      schizophrenia patients. The TMS data suggest that this deficit may not localize
      to the occipital cortex. However, TMS can be a useful tool for localizing
      processing deficits in schizophrenia.

PMID- 17207778
TI  - Decreases in dietary preference produce increased emotionality and risk for
      dietary relapse.
AB  - BACKGROUND: Obesity is a modern health epidemic, with the overconsumption of
      highly palatable, calorically dense foods as a likely contributor. Despite the
      known consequences of obesity, behavioral noncompliance remains high, supporting
      the powerful rewarding properties of such foods. We hypothesized that exposure to
      preferred diets would result in an amelioration of stress responsivity via
      activation of reward pathways that would be reversed during dietary withdrawal,
      increasing the risk for relapse and treatment failure. METHODS: Mice were exposed
      to preferred diets high in fat or carbohydrates for 4 weeks and then were
      withdrawn to house chow. Behavioral, physiologic, and biochemical assays were
      performed to examine changes in stress and reward pathways. RESULTS: These
      studies revealed significant changes in arousal and anxiety-like behaviors,
      limbic corticotropin-releasing factor expression, and expression of reward
      related signaling molecules in response to the highly preferred high-fat diet
      that was reversed by withdrawal. In a dietary-reinstatement model, mice withdrawn
      from the high-fat diet endured an aversive environment to gain access to the
      preferred food. CONCLUSIONS: Exposure to a highly preferred diet high in fat
      reduces stress sensitivity, whereas acute withdrawal from such a diet elevates
      the stress state and reduces reward, contributing to the drive for dietary
      relapse.

PMID- 17207779
TI  - Quantitative proteomic profiling of membrane proteins from the mouse brain
      cortex, hippocampus, and cerebellum using the HysTag reagent: mapping of
      neurotransmitter receptors and ion channels.
AB  - Analysis of the brain proteome and studying brain diseases through clinical
      biopsies and animal disease models require methods of quantitative proteomics
      that are sensitive and allow identification and quantification of low abundant
      membrane proteins from minute amount of tissue. Taking advantage of recently
      developed methods for isolation of membrane proteins from 10-20 mg brain tissue
      [Nielsen, P.Aa., Olsen, J.V., Podtelejnokov, A.V., Andersen, J.R., Mann, M.,
      Wisniewski, J.R., 2005. Proteomic mapping of brain plasma membrane proteins. Mol.
      Cell. Proteomics 4, 402--408] and the HysTag-quantification method [Olsen, J.V.,
      Andersen, J.R., Nielsen, P.Aa., Nielsen, M.L., Figeys, D., Mann, M., Wisniewski,
      J.R., 2004. HysTag---A novel proteomic qualification tool applied to differential
      analysis of membrane proteins from distinct areas of mouse brain. Mol. Cell.
      Proteomics 3, 82--92] we performed quantitative proteomic analysis of three
      functionally distinct compartments of mouse brain: cortex, hippocampus, and
      cerebellum. In total, 976 unique peptides corresponding to 555 unique proteins
      were quantified. Up to 20-fold differences in the levels of some proteins between
      brain areas were measured. For many quantified proteins--as for glutamate
      receptors, calcium channel subunits, and ATP-ases--an excellent correlation
      between our proteomic data and previously published mRNA expression levels or
      intensity of immunostaining was found. Our results clearly demonstrate
      differences in levels of membrane proteins mapped in distinct brain compartments
      and offer a technology that allows in depth study of brain membrane proteomes,
      such as mouse models of neurological diseases.

PMID- 17207780
TI  - Distribution of NMDA and AMPA receptor subunits at thalamo-amygdaloid dendritic
      spines.
AB  - Synapses onto dendritic spines in the lateral amygdala formed by afferents from
      the auditory thalamus represent a site of plasticity in Pavlovian fear
      conditioning. Previous work has demonstrated that thalamic afferents synapse onto
      LA spines expressing glutamate receptor (GluR) subunits, but the GluR subunit
      distribution at the synapse and within the cytoplasm has not been characterized.
      Therefore, we performed a quantitative analysis for alpha-amino-3-hydroxy-5
      methyl-4-isoxazole propionate (AMPA) receptor subunits GluR2 and GluR3 and N
      methyl-D-aspartate (NMDA) receptor subunits NR1 and NR2B by combining anterograde
      labeling of thalamo-amygdaloid afferents with postembedding immunoelectron
      microscopy for the GluRs in adult rats. A high percentage of thalamo-amygdaloid
      spines was immunoreactive for GluR2 (80%), GluR3 (83%), and NR1 (83%), while a
      smaller proportion of spines expressed NR2B (59%). To compare across the various
      subunits, the cytoplasmic to synaptic ratios of GluRs were measured within
      thalamo-amygdaloid spines. Analyses revealed that the cytoplasmic pool of GluR2
      receptors was twice as large compared to the GluR3, NR1, and NR2B subunits. Our
      data also show that in the adult brain, the NR2B subunit is expressed in the
      majority of in thalamo-amygdaloid spines and that within these spines, the
      various GluRs are differentially distributed between synaptic and non-synaptic
      sites. The prevalence of the NR2B subunit in thalamo-amygdaloid spines provides
      morphological evidence supporting its role in the fear conditioning circuit while
      the differential distribution of the GluR subtypes may reflect distinct roles for
      their involvement in this circuitry and synaptic plasticity.

PMID- 17207781
TI  - Changes in estrogen receptor-alpha mRNA in the mouse cortex during development.
AB  - Estrogen plays a critical role in brain development and is responsible for
      generating sex differences in cognition and emotion. Studies in rodent models
      have shown high levels of estrogen binding in non-reproductive areas of the brain
      during development, including the cortex and hippocampus, yet binding is
      diminished in the same areas of the adult brain. These binding studies
      demonstrated that estrogen receptors decline in the cortex during development but
      did not identify which of the two estrogen receptors was present. In the current
      study, we examined the expression of estrogen receptor alpha (ERalpha) and
      estrogen receptor beta (ERbeta) in the mouse cortex during the first month of
      life. Messenger RNA was isolated from cortical tissue taken from C57BL/6 mice on
      postnatal day (PND) 1, 4, 10, 18 and 25 and expression levels were determined by
      real-time PCR. ERalpha mRNA expression in the mouse cortex at PND 25 was
      significantly reduced as compared to PND 1 (p<0.01). ERbeta mRNA expression at
      PND 25 was significantly increased as compared to PND 1 (p<0.05). Although the
      increase in ERbeta mRNA was statistically significant, the ERbeta levels were
      extremely low in the isocortex compared to ERalpha mRNA levels, suggesting that
      ERalpha may play a more critical role in the developmental decrease of estradiol
      binding than ERbeta. Additionally, we measured ERalpha mRNA expression in
      organotypic explant cultures of cortex taken from PND 3 mice. Explants were
      maintained in vitro for 3 weeks. mRNA was isolated at several time points and
      ERalpha and ERbeta mRNA was measured by real-time RT-PCR. ERalpha and ERbeta mRNA
      levels reflected a similar pattern in vitro and in vivo, suggesting that signals
      outside the cortex are not needed for this developmental change. This study lays
      the groundwork for an understanding of the mechanisms of the developmental
      regulation of ERalpha mRNA.

PMID- 17207782
TI  - Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine
      model of cardiomyopathy.
AB  - OBJECTIVE: Cerium oxide (CeO2) nanoparticles have been shown to protect cells in
      culture from lethal stress, but no protection in vivo has been reported. Cardiac
      specific expression of monocyte chemoattractant protein (MCP)-1 in mice causes
      ischemic cardiomyopathy associated with activation of endoplasmic reticulum (ER)
      stress. The aim of this study was to assess the effects of CeO2 nanoparticles on
      cardiac function and remodeling as well as ER stress response in this murine
      model of cardiomyopathy. METHODS: MCP-1 transgenic mice (MCP mice) and wild-type
      controls were administered intravenously 15 nmol of CeO2 nanoparticles or vehicle
      only twice a week for 2 weeks. Cardiac function, myocardial histology,
      nitrotyrosine formation, expression of cytokines, and ER stress-associated genes
      were evaluated. RESULTS: Treatment with CeO2 nanoparticles markedly inhibited
      progressive left ventricular dysfunction and dilatation in MCP mice and caused a
      significant decrease in serum levels of MCP-1, C-reactive protein, and total
      nitrated proteins. The infiltration of monocytes/macrophages, accumulation of 3
      nitrotyrosine, apoptotic cell death, and expression of proinflammatory cytokines,
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 in the
      myocardium were markedly inhibited by CeO2 nanoparticles. Expression of the key
      ER stress-associated genes, including glucose-regulated protein 78 (Grp78),
      protein disulfide isomerase (PDI), and heat shock proteins (HSP25, HSP40, HSP70),
      were also suppressed by CeO2 nanoparticles. CONCLUSIONS: CeO2 nanoparticles
      protect against the progression of cardiac dysfunction and remodeling by
      attenuation of myocardial oxidative stress, ER stress, and inflammatory processes
      probably through their autoregenerative antioxidant properties.

PMID- 17207783
TI  - Mechanism of third signals provided by IL-12 and OX-40R ligation in eliciting
      therapeutic immunity following dendritic-tumor fusion vaccination.
AB  - Dendritic-tumor heterokaryons generated by electrofusion are highly immunogenic.
      In animal studies, a single vaccination was therapeutic for tumors established in
      the lung, skin, and brain. However, effective therapy required a third signal
      which could be provided by exogenous IL-12 or the agonistic anti-OX-40R
      monoclonal antibody (mAb). In this study, we investigated the mechanism and mode
      of actions of these two seemingly distinct adjuvants. In immunotherapy of the
      MCA205 sarcoma, administration of the neutralizing anti-IL-12 mAb nearly
      completely blocked the adjuvant effect of IL-12, but had minimal inhibitory
      effects on anti-OX-40R mAb. By contrast, in vivo administration of the
      antagonistic anti-OX-40L mAb inhibited the adjuvant effects of both IL-12 and
      anti-OX-40R mAb. Thus, a common pathway of endogenous OX-40 interaction is
      critical for the development of a therapeutic immune response. Analysis of the
      third signal mechanism revealed that in the absence of an adjuvant, vaccination
      with fusion hybrids led to IL-10 production without eliciting IFN-gamma secreting
      cells. The addition of IL-12 to vaccination suppressed IL-10 production and
      initiated sensitization of specific IFN-gamma secreting cells, resulting in a
      type 1-like antitumor immunity. These findings underscore the significance of the
      third signal in the design of dendritic cell-based cancer vaccines.

PMID- 17207784
TI  - Hepatocyte susceptibility to glyoxal is dependent on cell thiamin content.
AB  - Glyoxal, a reactive dicarbonyl, is detoxified primarily by the glyoxalase system
      utilizing glutathione (GSH) and by the aldo-keto reductase enzymes which utilizes
      NAD[P]H as the co-factor. Thiamin (Vitamin B(1)) is an essential coenzyme for
      transketolase (TK) that is part of the pentose phosphate pathway which helps
      maintain cellular NADPH levels. NADPH plays an intracellular role in regenerating
      glutathione (GSH) from oxidized GSH (GSSG), thereby increasing the antioxidant
      defenses of the cell. In this study we have focused on the prevention of glyoxal
      toxicity by supplementation with thiamin (3mM). Thiamin was cytoprotective and
      restored NADPH levels, glyoxal detoxification and mitochondrial membrane
      potential. Hepatocyte reactive oxygen species (ROS) formation, lipid peroxidation
      and GSH oxidation were decreased. Furthermore, hepatocytes were made thiamin
      deficient with oxythiamin (3mM) as measured by the decreased hepatocyte TK
      activity. Under thiamin deficient conditions a non-toxic dose of glyoxal (2mM)
      became cytotoxic and glyoxal metabolism decreased; while ROS formation, lipid
      peroxidation and GSH oxidation was increased.

PMID- 17207785
TI  - Multiscale representation for automatic identification of structures in medical
      images.
AB  - The identification of structures is a key step in several applications of medical
      imaging. In this work we propose a method for the identification of structures
      using a multiscale approach with inclusion of a priori information about the
      searched objects. After describing the image structures in the multiscale
      representation, a matching step determines which structure most likely
      corresponds to the target. Patterns are generated by previous application of the
      method to a set of images. We present a prototype for identifying structures in
      2D images. A set of experiments was carried out to evaluate the prototype leading
      to encouraging results.

PMID- 17207786
TI  - Biomechanical analysis of cervical spine sagittal stiffness characteristics.
AB  - The orientation of the loading, along which the minimum and maximum displacements
      occur, can be described as the principal axis. This work presents a model to
      determine extremums of the compliance of the cervical spine and corresponding
      principal axis, given the pose and flexibility of each functional cervical unit.
      As the cervical model of C(2)-C(7) section is flexed, it becomes tensionally
      stiffer and as the structure is extended, it becomes compressively stiffer. The
      opposite is true for the model including the atlanto-occipito-axial complex
      suggesting a compressively stiffer column as it is flexed and a tensionally
      stiffer structure as it is extended.

PMID- 17207787
TI  - Concentrations of biomarkers in spot urine samples need adjustment for variation
      in dilution--Comment on: "Distribution of urinary selenium and arsenic among
      pregnant women exposed to arsenic in drinking water" [Environ Res.
      2006;100(1):115-122].

PMID- 17207788
TI  - Time-dependent involvement of cAMP and cGMP in consolidation of object memory:
      studies using selective phosphodiesterase type 2, 4 and 5 inhibitors.
AB  - The present study investigated the time-dependent memory enhancing properties of
      three selective phosphodiesterase inhibitors (PDE-I) vardenafil (PDE5-I),
      rolipram (PDE4-I) and BAY 60-7550 (PDE2-I) in the object recognition task. In
      particular, the time-dependent involvement of cAMP and cGMP in memory
      consolidation was assessed by altering the time points of drug administration.
      Vardenafil (1 mg/kg, p.o.), rolipram (0.03 mg/kg, i.p.), and BAY 60-7550 (3
      mg/kg, p.o.) were tested in rats with a 24 h delay between the learning and the
      test trial. The PDE-Is were administered at different time points, i.e. directly
      after, 1 h, 3 h and 6 h after the first trial. Using a 24 h interval, vardenafil
      only showed an effect on object memory when injected directly after trial 1,
      rolipram only showed an improvement when injected 3 h after trial 1 and BAY 60
      7550 improved memory when injected either directly after or 3 h after trial 1. No
      treatment effects were found when the compounds were administered 1 h or 6 h
      after the first trial. Our results extend our previous data that different types
      of PDE-Is affect different stages of memory consolidation. Moreover, the present
      study provides further support that selective PDE-Is can influence memory
      consolidation in a time-dependent manner, assumingly by elevating central cAMP
      and cGMP levels.

PMID- 17207789
TI  - Anticlastogenic activity of morin against whole body gamma irradiation in Swiss
      albino mice.
AB  - Anticlastogenic activity of morin was explored against whole body gamma
      radiation, at a dose rate of 1.66 Gy/min in Swiss albino mice pretreated
      intraperitoneal or orally. Pretreatment with morin 10, 25, 50, 75, 100, 125, and
      150 mg/kg, i.p. delayed and reduced percentage mortality and increased mean
      survival times in mice irradiated with 10 Gy gamma radiation. Intraperitoneal
      route was found superior to oral route. An i.p. dose of 100 mg/kg was found to be
      the most effective dose in preventing radiation-induced weight loss, increasing
      the mean survival times and reducing percentage mortality. Morin (100 mg/kg)
      pretreatment effectively maintained spleen index (spleen weight/body weight x
      100) and stimulated endogenous spleen colony forming units. Pretreatment with
      morin (100 mg/kg) significantly reduced dead, inflammatory, and mitotic cells in
      irradiated mice jejunum along with a significant increase in goblet cells and
      rapidly multiplying crypt cells. Morin (100 mg/kg) also maintained the villus
      height close to normal, prevented mucosal erosion and basement membrane damage in
      irradiated jejunum. Nuclear enlargement in epithelial cells of jejunum was lower
      in morin treated mice compared to radiation control. Morin (100 mg/kg) also
      significantly elevated the endogenous antioxidant enzymes viz. glutathione S
      transferase (GST), superoxide dismutase (SOD) and reduced glutathione (GSH), in
      normal mice at 2, 4 and 8 h post treatment. Drastic decrease in endogenous
      enzymes (GSH, GST, catalase and SOD) and total thiols was observed in irradiated
      mice at 2, 4 and 8 h post irradiation, while pretreatment with morin (100 mg/kg)
      prevented this decrease. Morin (100 mg/kg) also elevated radiation LD(50) from
      9.2 to 10.1 Gy, indicating a dose modifying factor (DMF) of 1.11.

PMID- 17207790
TI  - Adiponectin, ghrelin, and leptin differentially influence human platelet and
      human vascular endothelial cell functions: implication in obesity-associated
      cardiovascular diseases.
AB  - A very strong epidemiological link exists between obesity, the metabolic
      syndrome, diabetes and diabetes-associated cardiovascular pathologies. For this
      reason the peripheral effects of the centrally-acting satiety adipokines,
      adiponectin and leptin, and of non-adipose-derived hormones with similar effects,
      like ghrelin, have received considerable attention. In this report, we have
      extended our previous studies of the pro-thrombotic effects of leptin and
      determined the effects of adiponectin or ghrelin on human platelet activation.
      Thus, while leptin stimulated human platelet aggregation and adhesion, addition
      of adiponectin or of ghrelin did not affect either aggregation or adhesion of
      these cells; even at supra-physiological concentrations. In addition, we compared
      the impact of these three important hormones on microvascular endothelial cell
      permeability, an important parameter of endothelial function that when impaired
      contributes to several vascular pathologies. While physiologically relevant
      concentrations of either leptin or adiponectin increased the integrity of the
      diffusion barrier formed by a monolayer of human microvascular endothelial cells,
      only supra-physiological concentrations of ghrelin had this effect. None of these
      agents reduced microvascular endothelial barrier function. Taken together, our
      data are consistent with the ideas that leptin activates human platelets and
      limits transendothelial cell diffusion but that adiponectin only influences
      endothelial cell permeability. In contrast, ghrelin had neither of these effects.
      We propose that these data identify important differences in the effects of
      leptin, adiponectin or ghrelin on microvascular endothelial cells and platelets
      and may provide a basis on which to pharmacologically manipulate the selective
      effects of these peptides on these cell types in human cardiovascular or
      thrombotic diseases associated with obesity.

PMID- 17207791
TI  - Behavioral effects of the R-(+)- and S-(-)-enantiomers of the dopamine D(1)-like
      partial receptor agonist SKF 83959 in monkeys.
AB  - Dopamine D(1)-like partial receptor agonists such as SKF 83959 have been proposed
      as potential candidates for the treatment of cocaine addiction. The present
      studies were conducted to further characterize SKF 83959 by pharmacologically
      evaluating effects of its R-(+)- and S-(-)-enantiomers, MCL 202 and MCL 201,
      respectively, on overt behavior (eye blinking) and schedule-controlled
      performance in squirrel monkeys. MCL 202, like the D(1) full receptor agonist SKF
      82958, produced dose-related increases in eye blinking and decreases in rates of
      fixed-ratio responding. However, the magnitude of effects of MCL 202 on eye
      blinking was less than observed with SKF 82958. In contrast to the effects of its
      R-(+) enantiomer, MCL 201 was relatively devoid of behavioral activity up to
      doses that were approximately 10-fold greater than MCL 202. Pretreatment with the
      selective D(1)-like receptor antagonist SCH 39166 dose-dependently antagonized
      increases in eye blinking produced by MCL 202, confirming the involvement of D(1)
      mechanisms in its effects. A dose-ratio analysis of the antagonism of effects of
      MCL 202 by SCH 39166 revealed an apparent pA(2) value of 7.675 with a slope of 
      0.78+/-0.04. In further studies, pretreatment with MCL 202 antagonized the
      effects of SKF 82958 on eye blinking and, like SCH 39166, schedule-controlled
      behavior in a dose-related manner. A dose-ratio analysis of the antagonist
      effects of MCL 202 on the SKF 82958-induced increases in eye blinking revealed
      ratios of 2.7, 4.8 and 31.1 for 0.1, 0.3 and 1.0 mg/kg dose of the antagonist,
      respectively, indicative of a significant change in the potency of SKF 82958.
      These results suggest that MCL 202, like its parent compound SKF 83959, has both
      D(1) receptor-mediated agonist and antagonist properties, consistent with its
      characterization as a partial agonist at the D(1)-like receptor. In addition, the
      inactivity of MCL 201, the S-(-)-enantiomer, suggests that the behavioral effects
      of SKF 83959 can be attributed primarily to the activity of its R-(+)-enantiomer.

PMID- 17207792
TI  - Anti-inflammatory activities of ent-16alphaH,17-hydroxy-kauran-19-oic acid
      isolated from the roots of Siegesbeckia pubescens are due to the inhibition of
      iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB inactivation.
AB  - To isolate the anti-inflammatory components in Siegesbeckia pubescens root, we
      performed activity-guided fractionation using a carrageenan-induced edema rat
      model. Antinociceptive effects were followed using acetic acid-induced abdominal
      constriction and hot plate tests in mice. Chloroform extract was subjected to
      silica gel and octadesyl silane (ODS) column chromatography, and a diterpene was
      isolated which was identified as ent-16alphaH,17-hydroxy-kauran-19-oic acid
      (siegeskaurolic acid). Pretreatment with siegeskaurolic acid (20 or 30 mg/kg/day,
      p.o.) exhibited anti-inflammatory and antinociceptive effects in these animal
      models. To investigate the mechanisms underlying this anti-inflammatory action,
      we investigated the effect of siegeskaurolic acid on lipopolysaccharide (LPS)
      induced responses in a murine macrophage cell line, RAW 264.7. Siegeskaurolic
      acid was found to significantly inhibit the productions of nitric oxide (NO),
      prostaglandin E(2) (PGE(2)), and tumor necrosis factor-alpha (TNF-alpha).
      Consistent with these findings, inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) proteins, and iNOS, COX-2, and TNF-alpha mRNAs were
      found to be inhibited by siegeskaurolic acid. Furthermore, siegeskaurolic acid
      inhibited the nuclear factor-kappaB (NF-kappaB) activation induced by LPS, and
      this was associated with the prevention of inhibitor kappaB degradation (I
      kappaB), and subsequently with decreased nuclear p65 and p50 protein levels.
      Taken together, our data indicate that the anti-inflammatory and antinociceptive
      properties of siegeskaurolic acid may be due to iNOS, COX-2 and TNF-alpha
      inhibition via the down-regulation of NF-kappaB binding activity.

PMID- 17207793
TI  - Loss of nuclear p21(Cip1/WAF1) during neoplastic progression to metastasis in
      gamma-irradiated p21 hemizygous mice.
AB  - p21(Cip1/WAF1) localizes to the nucleus in response to gamma-irradiation induced
      DNA damage and mediates a G(1) checkpoint arrest. Although gamma-irradiated
      p21(+/-) mice develop a broad spectrum of tumors, gamma-irradiated p21(-/-) mice
      develop significantly more metastatic cancers. To evaluate the expression of p21
      in tissues prone or resistant to tumorigenesis as a function of gamma
      irradiation, and to determine whether phenotypic loss of p21 heterozygosity
      occurs during tumor progression in p21(+/-) mice, tissues and tumors from gamma
      irradiated mice were evaluated immunohistochemically. The percentage of tumors in
      p21(+/-) mice that were nuclear p21-positive declined with progression to
      metastasis (p<0.0001). Benign tumors were more often p21-positive and comprised
      of larger subsets of nuclear p21-positive cells than were malignant tumors of the
      same histopathological type, while metastatic cancers were nuclear p21-negative
      (p=0.0003). Even when a primary cancer was comprised of a subset of nuclear p21
      positive cells, the metastatic foci of that same cancer were nuclear p21
      negative. Mesenchymal tumors, though rare, were more likely metastatic than were
      epithelial tumors (p=0.0004), and these were invariably nuclear p21-negative.
      Prepubescent epithelial tissues from which most tumors later originated in mice
      with reduced p21 gene dosage (i.e., harderian gland, ovary, small intestine, and
      lung) were p21 expressive within 4 h of gamma-irradiation (p=0.0625), so that
      p21/Ki67 ratios increased post-gamma-irradiation (p=0.03). In contrast, p21 did
      not localize to nuclei of cortical thymocytes, a tissue where tumorigenesis was
      not augmented by reduced p21 gene dosage. Cellular subclones of malignant tumors,
      especially those of mesenchymal cell origin, which lack nuclear p21 may more
      readily acquire the genetic alterations of the metastatic phenotype.

PMID- 17207794
TI  - Effects of the components of hormone therapy on matrix metalloproteinases in
      breast-cancer cells: an in vitro study.
AB  - A combination of E and progestogens significantly increased matrix
      metalloproteinase (MMP)-2 in both T47D cells (E(2)-medroxyprogesteroneacetate
      [MPA] and E(2)-P) and MCF-7 cells (E(2)-MPA, E(2)-P, and equilin-MPA). All
      combinations resulted in higher MMP-9 levels in MCF-7 cells, but higher MMP-9
      levels resulted only with equilin-norethinderone in T47D cells.

PMID- 17207795
TI  - Effect of embryo quality on pregnancy outcome following single embryo transfer in
      women with a diminished egg reserve.
AB  - OBJECTIVE: To evaluate independently the effect of blastomere number and degree
      of fragmentation on pregnancy outcome following single ETs in women with a
      decreased egg reserve. DESIGN: Retrospective cohort analysis. SETTING: In vitro
      fertilization center of a university-based practice. PATIENT(S): Women having a
      single ET related to a decreased egg reserve. A requirement for inclusion was a
      day 3 serum FSH >12 mIU/mL and < or =3 antral follicles on ultrasound.
      INTERVENTION(S): Patients received no or minimal stimulation with gonadotropins.
      MAIN OUTCOME MEASURE(S): Pregnancy rates (PRs) following single ETs were
      evaluated according to blastomere number (group 1, < or =4 cells; group 2, 5
      cells; group 3, 6 cells; group 4, 7 cells; and group 5, > or =8 cells) and
      fragmentation index (A, no fragmentation; B, 1-25% fragmentation; and C, >25%
      fragmentation). Embryo transfers and morphologic evaluation were performed on day
      3. RESULT(S): The clinical and delivered PRs according to blastomere number
      showed that 6-8-cell embryos were six times more likely to implant than 4-5-cell
      embryos (6.6% versus 40.4% clinical). Degree of fragmentation did not predict
      outcome nearly as well as blastomere number. The overall clinical and delivered
      PRs per transfer were 27.8% and 24.1%, respectively, and were 14.8% and 12.8% per
      retrieval, respectively, and were 9.0% and 7.3% per initiated cycle,
      respectively. CONCLUSION(S): Six, seven, or eight-cell embryos have equal chances
      of implanting in women with day 3 elevated serum FSH. The key finding is that
      these embryos do better than those with <6 blastomeres. These data may be helpful
      in women with a diminished ovarian reserve in attempting IVF with their own eggs
      or when choosing donor oocytes.

PMID- 17207796
TI  - Effects of arachnotoxin on intracellular pH and calcium in human spermatozoa.
AB  - OBJECTIVE: To determine the effect of arachnotoxin (ATx), a venom extracted from
      the Chilean spider Latrodectus mactans, on intracellular calcium ([Ca(2+)](i))
      and pH (pH(i)) in capacitated human spermatozoa. DESIGN: Spermatozoa were
      collected from fertile adult men (n = 8). Mobile spermatozoa were collected by
      the "swim up" technique and stimulated with the crude extract of ATx and with
      progesterone (P). SETTING: Hospital of the Federal University of Sao Paulo, Sao
      Paulo, Brazil. MAIN OUTCOME MEASURE(S): [Ca(2+)](i) was measured in fura2-AM
      loaded spermatozoa, and pH(i) was measured in spermatozoa loaded with the pH
      sensitive dye [(2',7')-bis (carboxymethyl)-(5,6)-carboxyfluorescein]-AM (BCECF).
      RESULT(S): The ATx and P induced a biphasic change in [Ca(2+)](i) consisting of a
      peak followed by a small but sustained elevation. The response to ATx was greatly
      reduced by pretreatment with P. The ATx caused intracellular acidification,
      whereas P induced alkalinization. Blockade of the NA(+)/H(+) exchanger with
      ethylisopropylamiloride (EIPA) sharply increased ATx-induced acidification.
      CONCLUSION(S): Arachnotoxin increased [Ca(2+)](i) through the opening of calcium
      channels and release of calcium from intracellular stores. The ATx reduced pH(i)
      in human sperm, possibly by inhibiting the Na(+)/H(+) exchanger.

PMID- 17207797
TI  - An estrogen metabolism-related polymorphism of the 17-alpha HSD gene is
      associated with perimenopausal body mass index.
AB  - In a cross-sectional study of 2,802 perimenopausal caucasian women, carriage of
      at least one mutated allele of the 17-alpha-hydroxysteroid dehydrogenase type 1
      (17-alpha HSD) vlV A-->C single nucleotide polymorphism (SNP) was associated with
      a significantly increased body mass index (mean 24.3 +/- 4.4 kg/m(2) vs. 23.5 +/-
      4.2 kg/m(2); P<.001), and obesity was more frequent among mutant allele carriers
      (P=.06; odds ratio 1.38; 95% confidence interval 0.97-1.95), providing evidence
      of 17-alpha HSD as a candidate gene of perimenopausal obesity.

PMID- 17207798
TI  - Methylation status of the SNRPN and HUMARA genes in testicular biopsy samples.
AB  - OBJECTIVE: To analyze the methylation status of two differentially inherited and
      methylated loci (the human androgen receptor [HUMARA] and the small nuclear
      ribonucleoprotein-associated polypeptide N [SNRPN] gene) in testicular biopsy
      samples, and to compare the results with microscopic evaluation. DESIGN:
      Retrospective study. SETTING: Infertility clinics and genetics laboratories.
      PATIENT(S): Twelve obstructive and 74 nonobstructive azoospermic men.
      INTERVENTION(S): Deoxyribonucleic acid samples from testicular biopsies and
      peripheral blood were modified with sodium bisulfite and amplified by methylation
      specific polymerase chain reaction assay. Polymerase chain reaction primers
      specific for the methylated regions of the HUMARA locus and for the methylated
      and unmethylated CpG islands of the SNRPN gene were used. MAIN OUTCOME MEASURE:
      Polymerase chain reaction product bands specific for methylated and unmethylated
      alleles. RESULT(S): Obstructive azoospermia patients were positive for
      spermatozoa and germ cells by all approaches (microscopic, HUMARA, and SNRPN
      analysis) with absolute consistency. In contrast, for the nonobstructive men,
      microscopy was consistent with SNRPN analysis as regards the presence of germ
      cells in 82% of the testicular tissues tested. Nonobstructive patients with
      maturation arrest were positive for the presence of germ cells only by HUMARA
      analysis, with 84% sensitivity. CONCLUSION(S): Methylation analysis of testicular
      tissue is consistent with microscopic analysis, in terms of the prevalence of
      germ cells and the stage of spermatogenic arrest in biopsy samples.

PMID- 17207799
TI  - Predicting factors for endometrial thickness during treatment with assisted
      reproductive technology.
AB  - OBJECTIVE: To discover the factors contributing to endometrial thickness, and to
      assess the impact of endometrial thickness on pregnancy rates (PRs) according to
      these factors. DESIGN: Retrospective study. SETTING: In vitro fertilization unit
      in a university hospital. PATIENT(S): All women with primary infertility and no
      previous pregnancies who underwent IVF treatment at the Chaim Sheba Medical
      Center, Tel Hashomer, Israel, between August 9, 2001-December 31, 2004.
      INTERVENTION: Measurement of endometrial thickness by the use of transvaginal
      ultrasound probe on the day that hCG was administered during an IVF cycle. MAIN
      OUTCOME MEASURE(S): Factors influencing endometrial thickness and the
      relationship between endometrial thickness and PRs. RESULT(S): The mean
      endometrial thickness decreased as a function of the patient's age. The thickest
      endometrium was found in patients <25 years of age (11.9 +/- 2.5 mm), and the
      thinnest endometrium was found in patients >40 years of age (9.6 +/- 2.3 mm).
      Other factors, such as E(2) levels, etiology of infertility, induction of
      ovulation protocol, and type of gonadotropin used, were also found to contribute
      to endometrial thickness. CONCLUSION(S): Our data support the case for an "aging"
      of the endometrium. The chances of achieving a thick endometrium for patients >40
      years of age are lower than for younger patients. Furthermore, a thicker
      endometrium is correlated with a higher PR only for patients >35 years of age.

PMID- 17207800
TI  - Detection of endometriosis with the use of plasma protein profiling by surface
      enhanced laser desorption/ionization time-of-flight mass spectrometry.
AB  - In this prospective case-control study, we determined the role of surface
      enhanced laser desorption and ionization time-of-flight mass spectrometry in the
      detection of histologically proven endometriosis. In the plasma of the group with
      endometriosis, there were 20 different protein peaks, and the classifier showed a
      sensitivity of 87.5% and a specificity of 80% in the diagnosis of endometriosis.

PMID- 17207801
TI  - A randomized, prospective study comparing laser-assisted hatching and assisted
      hatching using acidified medium.
AB  - OBJECTIVE: To compare the clinical outcomes of patients whose transferred embryos
      underwent either laser-assisted hatching or hatching with acidified medium.
      DESIGN: Randomized, prospective, double-blinded study. SETTING: University-based
      IVF center. PATIENT(S): Clinical outcomes following IVF were compared in 159
      patient cycles who randomly had all transferred embryos undergo laser-assisted
      hatching (Laser; n = 57) or hatching with acidified medium (Acid; n = 54).
      Patients whose embryos had zonae thickness <13 mum were not hatched (Thin; n = 8)
      and patients with > or =4 embryos at the 7- to 8-cell stage or higher on Day 3
      were transferred on Day 5 (Day 5; n = 40). MAIN OUTCOME MEASURE(S): Implantation
      rates, clinical pregnancy rates, ongoing pregnancy rates, multiple pregnancy
      rates. RESULT(S): No significant differences were noted in clinical, ongoing, or
      multiple pregnancy rates between the four groups. The implantation rate for Day 5
      transfers was significantly greater than both the Laser and Acid treatment
      groups. CONCLUSION: The use of a 1.48-micron infrared diode laser beam provides a
      safe and rapid method for performing assisted hatching and did not have a
      negative impact on patient care when compared to outcomes achieved using
      acidified medium.

PMID- 17207802
TI  - Moderately elevated levels of basal follicle-stimulating hormone in young
      patients predict low ovarian response, but should not be used to disqualify
      patients from attempting in vitro fertilization.
AB  - OBJECTIVE: To evaluate and compare IVF outcomes of patients within different age
      categories who had a normal basal FSH level with outcomes of patients with an
      elevated day 3 FSH level. DESIGN: Retrospective analysis. SETTING: Large, private
      IVF center. PATIENT(S): We analyzed 2,708 patients. Of these, 2,477 had normal
      basal FSH levels, and 231 had elevated basal FSH levels (> or =13.03 IU/L).
      Patients were segregated into various age groups. INTERVENTION: Follow-up. MAIN
      OUTCOME MEASURE(S): Outcomes of IVF overall, including cancellation rates, oocyte
      yield, and fertilization, implantation, and clinical pregnancy rates (PRs).
      RESULT(S): Cancellation rates were significantly higher in patients with elevated
      day 3 FSH levels compared with patients with normal FSH levels in all age groups.
      A significantly lower oocyte yield was observed in patients with elevated basal
      FSH. Fertilization rates were not affected by FSH levels. A significant decrease
      in the number of embryos available for transfer in patients > or =38 with an
      elevated day 3 FSH level was found. Implantation and clinical PRs were lower in
      patients >40 years of age who had an elevated day 3 FSH level when compared to
      same age patients with a normal day 3 FSH level. Loss rates were not
      significantly different. CONCLUSION(S): Young women with an elevated basal FSH
      level should be counseled differently than older women, and should be given
      adequate counseling and granted the opportunity to undergo an IVF cycle.

PMID- 17207803
TI  - Prophylactic vaginal hysterectomy for benign hydatidiform mole.

PMID- 17207804
TI  - Quantitative determination of wine highly volatile sulfur compounds by using
      automated headspace solid-phase microextraction and gas chromatography-pulsed
      flame photometric detection. Critical study and optimization of a new procedure.
AB  - The quantitative determination of wine volatile sulfur compounds by automated
      headspace solid-phase microextraction (HS-SPME) with a carboxen
      polydimethylsiloxane (CAR-PDMS) fiber and subsequent gas chromatography-pulsed
      flame photometric detection (GC-PFPD) has been evaluated. The direct extraction
      of the sulfur compounds in 5 ml of wine has been found to suffer from matrix
      effects and short linear ranges, problems which could not be solved by the use of
      different internal standards or by multiple headspace SPME. These problems were
      attributed to saturation of the fiber and to competitive effects between
      analytes, internal standards and other wine volatiles. Another problem was the
      oxidation of analytes during the procedure. The reduction in sample volume by a
      factor 50 (0.1 ml diluted with water or brine) brought about a reduction in the
      amount of sulfur compounds taken in the fiber by a factor just 3.3. Consequently,
      a new procedure has been proposed. In a sealed vial containing 4.9 ml of
      saturated NaCl brine, the air is thoroughly displaced with nitrogen, and the wine
      (0.1 ml) and the internal standards (0.02 ml) are further introduced with a
      syringe through the vial septum. This sample is extracted at 35 degrees C for 20
      min. This procedure makes a satisfactory determination possible of hydrogen
      sulfide, methanethiol, ethanethiol, dimethyl sulfide, diethyl sulfide and
      dimethyl disulfide. The linear dynamic ranges cover the normal ranges of
      occurrence of these analytes in wine with typical r2 between 0.9823 and 0.9980.
      Reproducibility in real samples ranges from 10 to 20% and repeatability is better
      than 10% in most cases. The method accuracy is satisfactory, with errors below
      20% for hydrogen sulfide and mostly below 10% for the other compounds. The
      proposed method has been applied to the analysis of 34 Spanish wines.

PMID- 17207805
TI  - Validation of a method using an achiral liquid chromatography sorbent and a
      circular dichroism detector. Analysis of the efaroxan enantiomers.
AB  - The known HPLC method using an achiral C8 silica sorbent and a circular dichroism
      (CD) detector for the determination of efaroxan enantiomeric excess has been
      validated. After optimization of the mobile phase, the enantiomers were detected
      at 278 nm offering maximum ellipticity between two optically active forms. The
      calibration curve of the anisotropy factor (g) versus the enantiomeric excess was
      linear with a correlation coefficient (r2) of 0.9985. The accuracy of the method
      was assessed by comparing the enantiomeric excess obtained by measuring the g
      factor (C8 column, CD and UV detections) with those determined by
      enantioselective HPLC (Chiralpak AD-H column, UV detection). Statistical tests
      (level of confidence of 95%) were assessed to compare the two orthogonal methods.
      The straight line gave a correlation coefficient of 0.9995, an intercept not
      significantly different from zero (0.0549) and a slope of 1.026. The precision
      evaluated on retention time (RSD<0.6%), g factor (RSD<8.3%) and CD peak area
      (RSD<7.5%) was suitable both in term of intra- and inter-day precisions. The
      proposed method has the advantages of being fast and precise without using
      expensive chiral column. Non-enantioselective HPLC-CD was suitable for the
      simultaneous determination of the optical and chemical purity of efaroxan.

PMID- 17207806
TI  - Hydrophobic interaction chromatography of proteins. I. The effects of protein and
      adsorbent properties on retention and recovery.
AB  - The contributions of protein and adsorbent properties to retention and recovery
      were examined for hydrophobic interaction chromatography (HIC) using eight
      commercially available phenyl media and five model proteins (ribonuclease A,
      lysozyme, alpha-lactalbumin, ovalbumin and BSA). The physical properties of the
      adsorbents were determined by inverse size exclusion chromatography (ISEC). The
      adsorbents examined differ from each other in terms of base matrix, ligand
      density, porosity, mean pore radius, pore size distribution (PSD) and phase
      ratio, allowing systematic studies to understand how these properties affect
      protein retention and recovery in HIC media. The proteins differ in such
      properties as adiabatic compressibility and molecular mass. The retention factors
      of the proteins in the media were determined by isocratic elution. The results
      show a very clear trend in that proteins with high adiabatic compressibility
      (higher flexibility) were more strongly retained. For proteins with similar
      adiabatic compressibilities, those with higher molecular mass showed stronger
      retention in Sepharose media, but this trend was not observed in adsorbents with
      polymethacrylate and polystyrene divinylbenzene base matrices. This observation
      could be related to protein recovery, which was sensitive to protein flexibility,
      molecular size, and conformation as well as the ligand densities and base
      matrices of the adsorbents. Low protein recovery during isocratic elution could
      affect the interpretation of protein selectivity results in HIC media. The
      retention data were fitted to a previously published retention model based on the
      preferential interaction theory, in terms of which retention is driven by release
      of water molecules and ions upon protein-adsorbent interaction. The calculated
      number of water molecules released was found to be statistically independent of
      protein retention strength and adsorbent and protein properties.

PMID- 17207807
TI  - Fluorescence and interactions with thiol compounds of Nile Red-adsorbed gold
      nanoparticles.
AB  - We have investigated the interactions between a variety of thiols and Nile Red
      adsorbed gold nanoparticles (NRAuNPs). After adding thiols to solutions of
      NRAuNPs, the solutions fluoresce strongly as a result of the displacement of a
      Nile Red-derived product from the surface of the AuNPs. We propose a mechanism
      for the formation of this NR product on the surface of AuNPs by conducting mass
      spectrometry, fluorescence, and capillary electrophoresis measurements. By
      recording the fluorescence changes of the NRAuNP solutions after addition of the
      thiols, we investigated the interactions between the thiols and NRAuNPs. Using
      the Langmuir isotherm model, we found that the displacement rate constants for
      thiols having one carboxyl residue, such as 3-mercaptopropionic acid, fall within
      the range 0.55-1.19 x 10(-2) s(-1). Thiols containing hydroxyl groups [e.g., 2
      mercaptoethanol (2-ME)] or amino groups [e.g., N-(2-mercaptopropionyl)glycine
      (MPG)], or that have flat structures on the AuNP surface, such as
      mercaptosuccinic acid, exhibit double-exponential kinetics with first rate
      constants of 0.51-2.83 x 10(-2) s(-1) and second rate constants of 6.0-23.4 x 10(
      4) s(-1). Our results reveal that steric effects and the charge density of the
      thiols both play important roles in determining the interactions with NRAuNPs.
      The interactions (displacement and/or induced aggregation) are also dependent on
      the size of NRAuNPs.

PMID- 17207808
TI  - Studies on the structure and miscibility of mixed Langmuir-Blodgett films of a
      double-armed dibenzo-18-crown-6 ether with stearic acid.
AB  - Reported here is the study on the structure of Langmuir-Blodgett (LB) films of
      double-armed dibenzo-18-crown-6 contain biphenyl (DACE) which are newly
      synthesized and mixed with stearic acid (SA). In addition, the miscibility of the
      two compounds was also tested by the measurement of the surface pressure-area (pi
      A) isotherms of DACE and DACE/SA with various proportions. It is noted that there
      is no phase segregation in the mixed monolayer film of DACE/SA. Upon calculation
      of the excess surface area, it is concluded that the SA molecule can enter into
      the crown ether ring, while an 18C6 ring can host a maximum of one SA molecule.
      The difference of spectroscopic properties of DACE in LB films and bulk solution
      has been investigated by ultraviolet-visible (UV-vis) and Fourier-transfer
      infrared (FTIR) measurements. Molecules of DACE exist in the mixed LB films as
      monomers in contrast to those in the concentrated solution as aggregates. The
      hydrocarbon chains in DACE and DACE/SA LB films are tilted to the normal of the
      substrate surface, but perpendicular to the dipole moment of CO. Both CO bonds in
      the phenyl ethers and carboxylic ester of DACE, and the long axes of phenyl rings
      are aligned nearly perpendicular to the substrate surface. Infrared spectra of
      mixed LB films of DACE/SA present further evidence that the SA molecules enter
      into the crown ether rings of DACE.

PMID- 17207809
TI  - Authors' response to the comments on "A new mechanistic Parachor model to predict
      dynamic interfacial tension and miscibility in multicomponent hydrocarbon
      systems" by F.M. Orr and K. Jessen.

PMID- 17207810
TI  - Evaporation from an ionic liquid emulsion.
AB  - The conditions during evaporation in a liquid crystal-in-ionic liquid
      microemulsion (LC/microEm) were estimated using the phase diagram of the system.
      The equations for selected tie lines were established and the coordinates
      calculated for the sites, at which the evaporation lines crossed the tie lines.
      These values combined with the coordinates for the phases connecting the tie
      lines were used to calculate the amounts and the composition of the fractions of
      the two phases present in the emulsion during the evaporation. One of the
      emulsion phases was a lamellar liquid crystal and high energy emulsification
      would lead to the liquid crystal being disrupted to form vesicles. Such a system
      tenders a unique opportunity to study the interaction between vesicles and normal
      micelles, which gradually change to inverse micelles over bi-continuous
      structures. The amount of vesicles in the liquid phase versus the fraction liquid
      crystal was calculated for two extreme cases of vesicle core size and shell
      thickness. The limit of evaporation while retaining the vesicle structure was
      calculated for emulsions of different original compositions assuming the minimum
      continuous liquid phase to be 50% of the emulsion.

PMID- 17207811
TI  - Incubation period, spore egestion and horizontal transmission of Nosema
      fumiferanae (Microsporidia: Nosematidae) in spruce budworm (Choristoneura sp.,
      Lepidoptera: Tortricidae): the role of temperature and dose.
AB  - Various instars of Choristoneura occidentalis were fed with a range of doses of
      Nosema fumiferanae and reared at 20, 24 and 28 degrees C to determine the
      influence of temperature and dose on the time to spore egestion and the number of
      spores egested in the frass. When larvae were fed in the third stadium, as few as
      10(2) spores per larva initiated infection, and both onset of spore egestion and
      the number of spores egested were affected by a complex relationship between
      temperature and inoculation dose. Onset of spore egestion varied from 11 to 15
      days postinoculation. At 20 degrees C, the onset was delayed and spore production
      decreased with increasing inoculation dose whereas at higher temperatures spores
      were first egested at the lowest dose and spore production increased with dose.
      When larvae were fed spores in the fifth and sixth stadium, no spores were
      egested because pupation occurred before completion of the incubation period. To
      assess the effect of temperature on horizontal transmission, Choristoneura
      fumiferana larvae fed with 10(4) N. fumiferanae spores per larva were reared with
      uninfected larvae at 15, 20 and 25 degrees C. At 15 degrees C, we observed the
      highest degree of horizontal transmission, defined by the largest change in N.
      fumiferanae prevalence, even though the density of spores available for
      horizontal transmission was the lowest. Infected adults eclosed later than
      uninfected adults and the time to eclosion was also dependent on sex and
      temperature. We relate our experimental findings to consequences for horizontal
      and vertical transmission of N. fumiferanae in spruce budworm populations.

PMID- 17207812
TI  - Limulus polyphemus hemocyanin: 10 A cryo-EM structure, sequence analysis,
      molecular modelling and rigid-body fitting reveal the interfaces between the
      eight hexamers.
AB  - The blue copper protein hemocyanin from the horseshoe crab Limulus polyphemus is
      among the largest respiratory proteins found in nature (3.5 MDa) and exhibits a
      highly cooperative oxygen binding. Its 48 subunits are arranged as eight hexamers
      (1x6mers) that form the native 8x6mer in a nested hierarchy of 2x6mers and
      4x6mers. This quaternary structure is established by eight subunit types (termed
      I, IIA, II, IIIA, IIIB, IV, V, and VI), of which only type II has been sequenced.
      Crystal structures of the 1x6mer are available, but for the 8x6mer only a 40 A 3D
      reconstruction exists. Consequently, the structural parameters of the 8x6mer are
      not firmly established, and the molecular interfaces between the eight hexamers
      are still to be defined. This, however, is crucial for understanding how
      allosteric transitions are mediated between the different levels of hierarchy.
      Here, we show the 10 A structure (FSC(1/2-bit) criterion) of the oxygenated
      8x6mer from cryo-electron microscopy (cryo-EM) and single-particle analysis.
      Moreover, we show its molecular model as obtained by DNA sequencing of subunits
      II, IIIA, IV and VI, and molecular modelling and rigid-body fitting of all
      subunit types. Remarkably, the latter enabled us to improve the resolution of the
      cryo-EM structure from 11 A to the final 10 A. The 10 A structure allows firm
      assessment of various structural parameters of the 8x6mer, the 4x6mer and the
      2x6mer, and reveals a total of 46 inter-hexamer bridges. These group as 11 types
      of interface: four at the 2x6mer level (II-II, II-IV, V-VI, IV-VI), three form
      the 4x6mer (V-V, V-VI, VI-IIIB/IV/V), and four are required to assemble the
      8x6mer (IIIA-IIIA, IIIA-IIIB, II-IV, IV-IV). The molecular model shows the amino
      acid residues involved, and reveals that several of the interfaces are
      intriguingly histidine-rich and likely to transfer allosteric signals between the
      different levels of the nested hierarchy.

PMID- 17207813
TI  - Functional characterization and conformational analysis of the Herpesvirus
      saimiri Tip-C484 protein.
AB  - Tyrosine kinase interacting protein (Tip) of Herpesvirus saimiri (HVS) activates
      the lymphoid-specific member of the Src family kinase Lck. The Tip:Lck
      interaction is essential for transformation and oncogenesis in HVS-infected
      cells. As there are no structural data for Tip, hydrogen-exchange mass
      spectrometry was used to investigate the conformation of a nearly full-length
      form (residues 1-187) of Tip from HVS strain C484. Disorder predictions suggested
      that Tip would be mostly unstructured, so great care was taken to ascertain
      whether recombinant Tip was functional. Circular dichroism and gel-filtration
      analysis indicated an extended, unstructured protein. In vitro and in vivo
      binding and kinase assays confirmed that purified, recombinant Tip interacted
      with Lck, was capable of activating Lck kinase activity strongly and was multiply
      phosphorylated by Lck. Hydrogen-exchange mass spectrometry of Tip then showed
      that the majority of backbone amide hydrogen atoms became deuterated after only
      10 s of labeling. Such a result suggested that Tip was almost totally
      unstructured in solution. Digestion of deuterium-labeled Tip revealed some
      regions with minor protection from exchange. Overall, it was found that, although
      recombinant Tip is still functional and capable of binding and activating its
      target Lck, it is largely unstructured.

PMID- 17207814
TI  - Effects of DksA, GreA, and GreB on transcription initiation: insights into the
      mechanisms of factors that bind in the secondary channel of RNA polymerase.
AB  - Escherichia coli DksA, GreA, and GreB have similar structures and bind to the
      same location on RNA polymerase (RNAP), the secondary channel. We show that GreB
      can fulfil some roles of DksA in vitro, including shifting the promoter-open
      complex equilibrium in the dissociation direction, thus allowing rRNA promoters
      to respond to changes in the concentration of ppGpp and NTPs. However, unlike
      deletion of the dksA gene, deletion of greB had no effect on rRNA promoters in
      vivo. We show that the apparent affinities of DksA and GreB for RNAP are similar,
      but the cellular concentration of GreB is much lower than that of DksA. When over
      expressed and in the absence of competing GreA, GreB almost completely
      complemented the loss of dksA in control of rRNA expression, indicating its
      inability to regulate rRNA transcription in vivo results primarily from its low
      concentration. In contrast to GreB, the apparent affinity of GreA for RNAP was
      weaker than that of DksA, GreA affected rRNA promoters only modestly in vitro
      and, even when over-expressed, GreA did not affect rRNA transcription in vivo.
      Thus, binding in the secondary channel is necessary but insufficient to explain
      the effect of DksA on rRNA transcription. Neither Gre factor was capable of
      fulfilling two other functions of DksA in transcription initiation: co-activation
      of amino acid biosynthetic gene promoters with ppGpp and compensation for the
      loss of the omega subunit of RNAP in the response of rRNA promoters to ppGpp. Our
      results provide important clues to the mechanisms of both negative and positive
      control of transcription initiation by DksA.

PMID- 17207815
TI  - Kinking the coiled coil--negatively charged residues at the coiled-coil
      interface.
AB  - The coiled coil is one of the most common protein-structure motifs. It is
      believed to be adopted by 3-5% of all amino acids in proteins. It comprises two
      or more alpha-helical chains wrapped around one another. The sequences of most
      coiled coils are characterized by a seven-residue (heptad) repeat, denoted
      (abcdefg)(n). Residues at the a and d positions define the helical interface
      (core) and are usually hydrophobic, though about 20% are polar or charged. We
      show that parallel coiled-coils have a unique pattern of their negatively charged
      residues at the core positions: aspartic acid is excluded from these positions
      while glutamic acid is not. In contrast the antiparallel structures are more
      permissive in their amino acid usage. We show further, and for the first time,
      that incorporation of Asp but not Glu into the a positions of a parallel coiled
      coil creates a flexible hinge and that the maximal hinge angle is being directly
      related to the number of incorporated mutations. These new computational and
      experimental observations will be of use in improving protein-structure
      predictions, and as rules to guide rational design of novel coiled-coil motifs
      and coiled coil-based materials.

PMID- 17207816
TI  - The first crystal structure of phosphofructokinase from a eukaryote: Trypanosoma
      brucei.
AB  - The crystal structure of the ATP-dependent phosphofructokinase (PFK) from
      Trypanosoma brucei provides the first detailed description of a eukaryotic PFK,
      and enables comparisons to be made with the crystal structures of bacterial ATP
      dependent and PPi-dependent PFKs. The structure reveals that two insertions (the
      17-20 and 329-348 loops) that are characteristic of trypanosomatid PFKs, but
      absent from bacterial and mammalian ATP-dependent PFKs, are located within and
      adjacent to the active site, and are in positions to play important roles in the
      enzyme's mechanism. The 90 residue N-terminal extension forms a novel domain that
      includes an "embracing arm" across the subunit boundary to the symmetry-related
      subunit in the tetrameric enzyme. Comparisons with the PPi-dependent PFK from
      Borrelia burgdorferi show that several features thought to be characteristic of
      PPi-dependent PFKs are present in the trypanosome ATP-dependent PFK. These two
      enzymes are generally more similar to each other than to the bacterial or
      mammalian ATP-dependent PFKs. However, there are critical differences at the
      active site of PPi-dependent PFKs that are sufficient to prevent the binding of
      ATP. This crystal structure of a eukaryotic PFK has enabled us to propose a
      detailed model of human muscle PFK that shows active site and other differences
      that offer opportunities for structure-based drug discovery for the treatment of
      sleeping sickness and other diseases caused by the trypanosomatid family of
      protozoan parasites.

PMID- 17207817
TI  - GABA-A2 receptor subunit gene (GABRA2) polymorphisms and risk for alcohol
      dependence.
AB  - Gamma-aminobutyric acid (GABA) A receptors are believed to mediate some of the
      physiological and behavioral actions of ethanol. Recent studies have suggested
      that genetic variants of the GABA-A receptor alpha2 subunit gene (GABRA2) are
      associated with alcohol dependence. The aim of this study is to confirm and
      extend the role of GABRA2 haplotypes in the liability to alcohol dependence. 291
      (231 male) treatment-seeking alcohol-dependent individuals and 295 (153 male)
      control subjects were enrolled into the study. Characteristics of alcohol
      dependence were obtained using the SSAGA (semi-structured assessment of the
      genetics of alcoholism, German Version). Genotyping of 10 SNPs across the GABRA2
      gene was performed following previous reports and using PCR. One genetic variant
      was detected to significantly differ between alcohol-dependent subjects and
      controls. Two common 8 SNP haplotypes and their complementary alleles were
      identified containing this SNP and were present in 89.9% of controls and 93.4% of
      the alcohol-dependent individuals. One of the haplotypes (T-C-A-C-A-T-T-C) was
      significantly associated with alcohol dependence and characteristics of alcohol
      withdrawal and severity of alcohol dependence (delirium tremens, withdrawal
      seizures). These findings support and extend the three previous studies
      implicating a GABA-A receptor subunit as contributing to the genetic risk for
      alcohol dependence. Possible implications of these findings are discussed.

PMID- 17207818
TI  - Mild head injury--a close relationship between motor function at 1 week post
      injury and overall recovery at 3 and 6 months.
AB  - Based on previous findings of impaired eye and arm motor control after mild
      closed head injury (CHI), this study examined whether early eye and arm motor
      function, and the level of post-injury cerebral dysfunction manifested in motor
      control, relates systematically to recovery at 3 and 6 months after mild CHI. At
      1 week post-injury, we assessed oculomotor function, upper-limb visuomotor
      performance, and cognitive status in 37 mild CHI patients. Re-examination at 3
      and 6 months determined outcome in terms of postconcussional symptoms and
      performance of everyday tasks, as assessed by the Rivermead Postconcussion
      Symptoms Questionnaire, the Rivermead Head Injury Follow-up Questionnaire and the
      SF-36 Health Survey. We then examined the association of early motor function,
      cognitive status and self-reported health condition with outcome using linear
      regression. Motor-based regression models explained a high proportion of the
      variance in outcome (70-89%), with motor function at 1 week being more closely
      related to outcome at 3 and 6 months than early psychometric assessment (13-32%)
      or self-reported health status (54-79%). These motor-based models incorporated
      subcortical/subconscious motor functions alongside motor functions that are
      subject to volitional control and are primarily mediated by frontal, parietal and
      temporal cortical brain regions. Early assessment of eye and arm motor function
      may help in improving accuracy of outcome prediction after mild CHI. Such
      assessment may assist in the better targeting of early health care intervention
      and help decrease head-trauma-related morbidity and rehabilitation costs.

PMID- 17207819
TI  - International collaboration on marine bioinvasions--the ICES response.
AB  - The International Council for the Exploration of the Sea (ICES) noted the risks
      associated with uncontrolled species introductions and transfers more than 40
      years ago and launched two working groups to address the issue, i.e. the ICES
      Working Group on Introductions and Transfers of Marine Organisms (WGITMO) to deal
      with the movement of non-indigenous species for e.g. aquaculture purposes and the
      ICES/IOC/IMO Working Group on Ballast and Other Ship Vectors which focuses on
      species movements with ships. Both groups are actively working until today and
      the key achievements of the groups are outlined.

PMID- 17207820
TI  - Comparison between anthropogenic hydrocarbons and magnetic susceptibility in
      sediment cores from the Santos Estuary, Brazil.

PMID- 17207821
TI  - Genotoxic effects of alcohol in human peripheral lymphocytes modulated by ADH1B
      and ALDH2 gene polymorphisms.
AB  - Ethanol is almost totally broken down by oxidative metabolism in vivo. Ethanol
      per se is considered to be neither carcinogenic, mutagenic nor genotoxic.
      However, during the metabolic conversion of ethanol to acetaldehyde and acetate,
      the organism is exposed to both ethanol and acetaldehyde and therefore ethanol is
      suspected to be co-carcinogenic. The genetic polymorphisms of alcohol
      dehydrogenase-2 (ADH1B) and acetaldehyde dehydrogenase-2 (ALDH2) influence the
      metabolism of alcohol. The ADH1B*1/*1 genotype encodes the low-activity form of
      ADH1B, and ALDH2*1/*2 and ALDH2*2/*2 genotype encode inactive ALDH2. The aim of
      this study was to test the hypothesis that polymorphisms of the ADH1B and ALDH2
      genes are significantly associated with genotoxicity induced by alcohol drinking,
      measured using the cytokinesis-block micronucleus (CBMN) assay, an established
      biomarker of genome instability, in peripheral blood lymphocytes of 286 healthy
      Japanese men. There was a significant trend for the mean micronuclei (MN)
      frequency in habitual or moderate drinkers without a smoking habit to increase as
      the numbers of the *1 allele in ADH1B increased (P=0.039 or P=0.029) and the *2
      allele in ALDH2 increased (P=0.019 or P=0.037). A logistic regression analysis
      showed that the number of subjects with MN frequency levels more than median
      value of MN (3.0) was significantly higher in the subjects with the ADH1B*1
      allele as adjusted estimates (OR 2.08, 95% C.I. 1.24-3.48), when the OR for the
      subjects with the ADH1B*2/*2 genotype was defined as 1.00. The number of subjects
      with MN frequency levels more than median value of MN was also significantly
      higher in the subjects with the ALDH2*2 allele as adjusted estimates (OR 1.79,
      95% C.I. 1.04-3.11), when the OR for the subjects with the ALDH2*1/*1 genotype
      was defined as 1.00. The results of this study have identified important novel
      associations between ADH1B/ALDH2 polymorphisms and genotoxicity in alcohol
      drinkers.

PMID- 17207822
TI  - Biotransformation of raspberry ketone and zingerone by cultured cells of
      Phytolacca americana.
AB  - The biotransformation of raspberry ketone and zingerone were individually
      investigated using cultured cells of Phytolacca americana. In addition to (2S)-4
      (4-hydroxyphenyl)-2-butanol (2%), (2S)-4-(3,4-dihydroxyphenyl)-2-butanol (5%), 4
      [4-(beta-d-glucopyranosyloxy)phenyl]-2-butanone (19%), 4-[(3S)-3
      hydroxybutyl]phenyl-beta-d-glucopyranoside (23%), and (2S)-4-(4-hydroxyphenyl)but
      2-yl-beta-d-glucopyranoside (20%), two biotransformation products, i.e., 2
      hydroxy-4-[(3S)-3-hydroxybutyl]phenyl-beta-d-glucopyranoside (12%) and 2-hydroxy
      5-[(3S)-3-hydroxybutyl]phenyl-beta-d-glucopyranoside (11%), were isolated from
      suspension cells after incubation with raspberry ketone for three days. On the
      other hand, two compounds, i.e., (2S)-4-(4-hydroxy-3-methoxyphenyl)but-2-yl-beta
      d-glucopyranoside (17%) and (2S)-2-(beta-d-glucopyranosyloxy)-4-[4-(beta-d
      glucopyranosyloxy)-3-methoxyphenyl]butane (16%), together with (2S)-4-(4-hydroxy
      3-methoxyphenyl)-2-butanol (15%), 4-[4-(beta-d-glucopyranosyloxy)-3
      methoxyphenyl]-2-butanone (21%), and 4-[(3S)-3-hydroxybutyl]-2-methoxyphenyl-beta
      d-glucopyranoside (24%) were obtained upon addition of zingerone. Cultured cells
      of P. americana can reduce, and regioselectively hydroxylate and glucosylate,
      these food ingredients to their beta-glycosides.

PMID- 17207823
TI  - Anthocyanin 3-galactosides from Cornus alba 'Sibirica' with glucosidation of the
      B-ring.
AB  - The three anthocyanins, delphinidin 3-O-beta-galactopyranoside-3',5'-di-O-beta
      glucopyranoside (1), delphinidin 3-O-beta-galactopyranoside-3'-O-beta
      glucopyranoside (2) and cyanidin 3-O-beta-galactopyranoside-3'-O-beta
      glucopyranoside (3), and the 3-O-beta-galactopyranosides of delphinidin (4) and
      cyanidin (5) were isolated from the bluish white berries and compound umbel of
      Siberian dogwood, Cornus alba 'Sibirica'. The ornamental autumn leaves and the
      characteristic purplish red bark of this variety were found to contain only
      pigment 5.

PMID- 17207824
TI  - Microbial metabolism of steviol and steviol-16alpha,17-epoxide.
AB  - Steviol (2) possesses a blood glucose-lowering property. In order to produce
      potentially more- or less-active, toxic, or inactive metabolites compared to
      steviol (2), its microbial metabolism was investigated. Incubation of 2 with the
      microorganisms Bacillus megaterium ATCC 14581, Mucor recurvatus MR 36, and
      Aspergillus niger BCRC 32720 yielded one new metabolite, ent-7alpha,11beta,13
      trihydroxykaur-16-en-19-oic acid (7), together with four known related
      biotransformation products, ent-7alpha,13-dihydroxykaur-16-en-19-oic acid (3),
      ent-13-hydroxykaur-16-en-19-alpha-d-glucopyranosyl ester (4), ent-13,16beta,17
      trihydroxykauran-19-oic acid (5), and ent-13-hydroxy-7-ketokaur-16-en-19-oic acid
      (6). The preliminary testing of antihyperglycemic effects showed that 5 was more
      potent than the parent compound (2). Thus, the microbial metabolism of steviol
      16alpha,17-epoxide (8) with M. recurvatus MR 36 was continued to produce higher
      amounts of 5 for future study of its action mechanism. Preparative-scale
      fermentation of 8 yielded 5, ent-11alpha,13,16alpha,17-tetrahydroxykauran-19-oic
      acid (10), ent-1beta,17-dihydroxy-16-ketobeyeran-19-oic acid (11), and ent
      7alpha,17-dihydroxy-16-ketobeyeran-19-oic acid (13), together with three new
      metabolites: ent-13,16beta-dihydroxykauran-17-acetoxy-19-oic acid (9), ent
      11beta,13-dihydroxy-16beta,17-epoxykauran-19-oic acid (12), and ent
      11beta,13,16beta,17-tetrahydroxykauran-19-oic acid (14). The structures of the
      compounds were fully elucidated using 1D and 2D NMR spectroscopic techniques, as
      well as HRFABMS. In addition, a GRE (glucocorticoid responsive element)-mediated
      luciferase reporter assay was used to initially screen the compounds 3-5, and 7
      as glucocorticoid agonists. Compounds 4, 5 and 7 showed significant effects.

PMID- 17207825
TI  - Comment on: Community support is associated with better antiretroviral treatment
      outcomes in a resource-limited rural district in Malawi.

PMID- 17207826
TI  - Physicochemical characterization of deflazacort: thermal analysis,
      crystallographic and spectroscopic study.
AB  - The solid state properties of deflazacort (1-(1beta,16alpha)-21-(acetyloxy)-11
      hydroxy-2'-methyl-5'H-pregna-1,4-dieno[17,16-d]oxazole-3,20-dione, 1) were
      investigated using differential scanning calorimetry (DSC), thermogravimetry
      (TG), single-crystal X-ray diffraction, solid and liquid nuclear magnetic
      resonance spectroscopy ((13)C NMR), Fourier transform infrared and Raman
      spectroscopy (FTIR and FT Raman). From the trends observed in the crystal
      structure and spectral data some conclusions can be made about hydrogen bonding,
      molecular conformation and crystal packing. Compound 1 crystallizes in an
      orthorhombic cell, space group P2(1)2(1)2(1) and the following lattice
      parameters: a=11.2300(5), b=12.8161(8), c=16.171(1)A, V: 2327.4(2)A(3), D(c):
      1.260g/cm(3), R1=0.0479, wR2=0.1012. The crystal structure is stabilized by intra
      and intermolecular interactions, which provides for a very closely packed form.
      The NMR data indicated that 1 shows a similar conformation in solid and liquid
      state; while, thermal data revealed that 1 follows a monophasic pattern with a
      DSC melting peak at 258.4 degrees C (DeltaH 99.7Jg(-1), n=3), indicating that 1
      is thermally stable as solid; but, as liquid is unstable to undergo a thermal
      decomposition reaction. The reactivity of 1 toward light and moisture was
      examined via DSC and TLC. The data indicated that 1 do not interact with water to
      give hydrated forms or decomposition products; however, light degrades 1.

PMID- 17207827
TI  - Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass
      spectrometric identification of urinary metabolites.
AB  - 4-Hydroxyandrost-4-ene-3,17-dione is a second generation, irreversible aromatase
      inhibitor and commonly used as anti breast cancer medication for postmenopausal
      women. 4-Hydroxytestosterone is advertised as anabolic steroid and does not have
      any therapeutic indication. Both substances are prohibited in sports by the World
      Anti-Doping Agency, and, due to a considerable increase of structurally related
      steroids with anabolic effects offered via the internet, the metabolism of two
      representative candidates was investigated. Excretion studies were conducted with
      oral applications of 100mg of 4-hydroxyandrostenedione or 200mg of 4
      hydroxytestosterone to healthy male volunteers. Urine samples were analyzed for
      metabolic products using conventional gas chromatography-mass spectrometry
      approaches, and the identification of urinary metabolites was based on reference
      substances, which were synthesized and structurally characterized by nuclear
      magnetic resonance spectroscopy and high resolution/high accuracy mass
      spectrometry. Identified phase-I as well as phase-II metabolites were identical
      for both substances. Regarding phase-I metabolism 4-hydroxyandrostenedione (1)
      and its reduction products 3beta-hydroxy-5alpha-androstane-4,17-dione (2) and
      3alpha-hydroxy-5beta-androstane-4,17-dione (3) were detected. Further reductive
      conversion led to all possible isomers of 3xi,4xi-dihydroxy-5xi-androstan-17-one
      (4, 6-11) except 3alpha,4alpha-dihydroxy-5beta-androstan-17-one (5). Out of the
      17beta-hydroxylated analogs 4-hydroxytestosterone (18), 3beta,17beta-dihydroxy
      5alpha-androstan-4-one (19), 3alpha,17beta-dihydroxy-5beta-androstan-4-one (20),
      5alpha-androstane-3beta,4beta,17beta-triol (21), 5alpha-androstane
      3alpha,4beta,17beta-triol (26) and 5alpha-androstane-3alpha,4alpha,17beta-triol
      (28) were identified in the post administration urine specimens. Furthermore 4
      hydroxyandrosta-4,6-diene-3,17-dione (29) and 4-hydroxyandrosta-1,4-diene-3,17
      dione (30) were determined as oxidation products. Conjugation was diverse and
      included glucuronidation and sulfatation.

PMID- 17207828
TI  - The search of the target of promotion: Phenylbenzoate esterase activities in hen
      peripheral nerve.
AB  - Certain esterase inhibitors, such as carbamates, phosphinates and sulfonyl
      halides, do not cause neuropathy as some organophosphates, but they may
      exacerbate chemical or traumatic insults to axons. This phenomenon is called
      promotion of axonopathies. Given the biochemical and toxicological
      characteristics of these compounds, the hypothesis was made that the target of
      promotion is a phenyl valerate (PV) esterase similar to neuropathy target
      esterase (NTE), the target of organophosphate induced delayed polyneuropathy.
      However, attempts to identify a PV esterase in hen peripheral nerve have been, so
      far, unsuccessful. We tested several esters, other than PV, as substrates of
      esterases from crude homogenate of the hen peripheral nerve. The ideal substrate
      should be poorly hydrolysed by NTE but extensively by enzyme(s) that are
      insensitive to non-promoters, such as mipafox, and sensitive to promoters, such
      as phenyl methane sulfonyl fluoride (PMSF). When phenyl benzoate (PB) was used as
      substrate, about 65% of total activity was resistant to the non-promoter mipafox
      (up to 0.5 mM, 20 min, pH 8.0), that inhibits NTE and other esterases. More than
      90% of this resistant activity was sensitive to the classical promoter PMSF (1
      mM, 20 min, pH 8.0) with an IC(50) of about 0.08 mM (20 min, pH 8.0). On the
      contrary, the non-promoter p-toluene sulfonyl fluoride caused only about 10%
      inhibition at 0.5 mM. Several esterase inhibitors including, paraoxon, phenyl
      benzyl carbamate, di-n-butyl dichlorovinyl phosphate and di-isopropyl
      fluorophosphate, were tested both in vitro and in vivo for inhibition of this PB
      activity. Mipafox-resistant PMSF-sensitive PB esterase activity(ies) was
      inhibited by promoters but not by non promoters and neuropathic compounds.

PMID- 17207829
TI  - Construction and characterization of a herpes simplex virus type I recombinant
      expressing green fluorescent protein: acute phase replication and reactivation in
      mice.
AB  - A recombinant HSV-1 virus expressing EGFP from the HCMV major immediate early
      promoter (KOS-CMVGFP) was constructed to monitor viral replication and spread in
      vitro and in mice. KOS-CMVGFP replicated as efficiently as wild-type virus,
      strain KOS, in single cycle growth experiments in Vero cells indicating that the
      recombinant virus has no significant growth defects in vitro. Following ocular
      inoculation of mice, KOS-CMVGFP exhibited slight but statistically significant
      reductions in mouse tear film titers relative to wild-type virus. Progression of
      virus infection of the eyes, periocular tissue, and snout was readily followed by
      fluorescence microscopy. Insertion of the EGFP expression cassette into the KOS
      genome had no effect on the efficiency of establishment of latency as determined
      by quantitative competitive PCR of viral genomes in latently infected TG. KOS
      CMVGFP reactivated with wild-type kinetics and efficiency by explant
      cocultivation, but exhibited a significant delay in the kinetics and a modest
      reduction in the efficiency of reactivation compared to KOS in the more sensitive
      TG cell culture model. Notably, EGFP expression preceded the detection of
      infectious virus by greater than 24 h in both ex vivo models and thus is a useful
      marker of the early stages in the induction of reactivation.

PMID- 17207830
TI  - Avian-virus-like receptor specificity of the hemagglutinin impedes influenza
      virus replication in cultures of human airway epithelium.
AB  - A non-optimal receptor-binding specificity of avian influenza viruses is believed
      to hamper their replication in humans; however, the magnitude of this restriction
      remains undefined. Here we generated recombinant viruses, R1 and R2, that
      differed solely by two amino acids in the receptor-binding site of their
      hemagglutinin (HA). R1 harbored the original HA of the pandemic human virus
      A/Hong Kong/1/68 (H3N2), whereas R2 was the L226Q/S228G HA mutant with avian
      virus-like receptor specificity. In differentiated cultures of human tracheo
      bronchial epithelial cells, R1 preferentially infected non-ciliated cells,
      whereas R2 predominantly infected ciliated cells indicating that cell tropism was
      determined by the viral receptor specificity. In the course of multi-cycle
      replication in these cultures, R2 spread less efficiently and grew to 2-10-fold
      lower titers than did R1. These results for the first time estimate the level of
      receptor-dependent restriction of avian influenza viruses in human airway
      epithelium. They support a theory that alteration of the receptor specificity of
      an avian virus could facilitate its human-to-human transmission.

PMID- 17207831
TI  - Absence of flash-lag when judging global shape from local positions.
AB  - When a flash is presented aligned with a moving stimulus, the former is perceived
      to lag behind the latter (the flash-lag effect). We study whether this
      mislocalization occurs when a positional judgment is not required, but a
      veridical spatial relationship between moving and flashed stimuli is needed to
      perceive a global shape. To do this, we used Glass patterns that are formed by
      pairs of correlated dots. One dot of each pair was presented moving and, at a
      given moment, the other dot of each pair was flashed in order to build the Glass
      pattern. If a flash-lag effect occurs between each pair of dots, we expect the
      best perception of the global shape to occur when the flashed dots are presented
      before the moving dots arrive at the position that physically builds the Glass
      pattern. Contrary to this, we found that the best detection of Glass patterns
      occurred for the situation of physical alignment. This result is not consistent
      with a low-level contribution to the flash-lag effect.

PMID- 17207832
TI  - The role of familiarity in three-dimensional view-transferability of face
      identity adaptation.
AB  - Recent studies show that face adaptation effects partially transfer across three
      dimensional viewpoint change. Here we investigated whether the degree of
      adaptation transfer is mediated by experience with a face. We manipulated face
      familiarity and measured identity aftereffects both within- and across-viewpoint.
      Familiarity enhanced the overall strength of identity adaptation as well as the
      degree to which adaptation transferred across-viewpoint change. These findings
      support the idea that transfer effects in adaptation vary as a function of
      experience with particular faces, and suggest the use of adaptation as a tool for
      tracking face representations as they develop.

PMID- 17207833
TI  - Hydrogen-dependent denitrification of water in an anaerobic submerged membrane
      bioreactor coupled with a novel hydrogen delivery system.
AB  - Hydrogen-dependent denitrification has gained significant attention due to its
      potential economic advantage over heterotrophic denitrification. However,
      effective hydrogen delivery and biomass retention under anaerobic conditions are
      significant challenges to implementation of this process. An innovative
      hydrogenotrophic denitrification system, that addresses these challenges,
      consisting of an anaerobic submerged membrane bioreactor (MBR) and a novel
      hydrogen delivery unit, was evaluated for removal of nitrate from a synthetic
      groundwater feed. The hydrogen delivery unit was designed to release hydrogen
      supersaturated water to the reactor and was efficient in hydrogen delivery,
      providing complete mass transfer. The anaerobic submerged MBR was successful in
      both reducing nitrate from 25 mg NO(3)-Nl(-1) to below detection and separating
      biomass from treated water to produce effluent free of suspended solids. Nitrogen
      gas produced during denitrification was internally recycled to effectively
      achieve membrane scouring and reactor mixing. The total organic carbon was
      similar to that of the incoming feed water, averaging approximately 6 mgl(-1).

PMID- 17207834
TI  - Comparison of sulfonated and other micropollutants removal in membrane bioreactor
      and conventional wastewater treatment.
AB  - Membrane bioreactors (MBRs) were compared with conventional activated sludge
      systems (CAS) for micropollutant degradation, in laboratory-scale spiking
      experiments with synthetic and real domestic wastewater. The target
      micropollutants were polar in nature and represented a broad range in
      biodegradability. The experimental data indicated that MBR treatment could
      significantly enhance removal of the micropollutants 1,6- and 2,7-naphthalene
      disulfonate (NDSA) and benzothiazole-2-sulfonate. 1,5-NDSA, EDTA and diclofenac
      were not removed in either the MBR or the CAS. The other compounds were equally
      well degraded in both systems. For 1,3-naphthalene disulfonate, the existence of
      a minimum threshold level for degradation could be demonstrated. Although MBRs
      could not always make a difference in the overall removal efficiencies achieved,
      they showed reduced lag phases for degradation and a stronger memory effect,
      which implies that they may respond quicker to variable influent concentrations.
      Finally, micropollutant removal also turned out to be less sensitive to system
      operational variables.

PMID- 17207835
TI  - Persistent organic pollutants, brominated flame retardants and synthetic musks in
      fish from remote alpine lakes in Switzerland.
AB  - Remote alpine lakes do not receive any direct aquatic inputs from anthropogenic
      activities. Therefore, these ecosystems may receive persistent organic compounds
      (POPs) by direct atmospheric deposition, only. Consequently, fish dwelling in
      these ecosystems represent an excellent indicator for the long-term atmospheric
      input of bioaccumulating and persistent contaminants. In the present study, fish
      from seven remote alpine lakes, located between 2062 and 2637 m above sea level
      in south eastern Switzerland (Grisons), were investigated. Lipid-based fish
      tissue concentrations of pesticides including dichlorodiphenyltrichloroethane
      (DDT) and its transformation products (2,4'-DDT, 4,4'-DDT, 2,4'
      dichlorodiphenyldichloroethane (DDD), 4,4'-DDD, 2,4'
      dichlorodiphenyldichloroethene (DDE), 4,4'-DDE), as well as dieldrin, heptachlor
      exo-epoxide (HPEX), hexachlorobenzene (HCB), hexachlorocyclohexanes (HCH),
      polychlorinated biphenyls (PCB), polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/F), and polybrominated diphenyl ethers (PBDE) were measured.
      In addition, seven synthetic musk compounds (Crysolide (ADBI), Phantolide (AHMI),
      Fixolide (AHTN), Traseolide (ATII), Galaxolide (HHCB), musk ketone (MK), and musk
      xylene (MX)) were determined. Concentrations of PCB, PCDD/F, and PBDE were in the
      same range as in fish from the major lakes situated in the Swiss plateau,
      indicating mainly atmospheric input of these persistent compounds. In contrast,
      concentrations of synthetic musks which are used as fragrances in laundry
      detergents and cosmetic products were distinctly lower than concentrations in
      fish from Swiss plateau lakes which receive inputs from waste water treatment
      plants.

PMID- 17207836
TI  - Depuration of PCBs and DDTs in mullet under captivity clean conditions.
AB  - Contaminated mullet (Mugil cephalus) from Douro estuary was allowed to depurate
      in clean water and fed with uncontaminated food. Levels of PCBs and DDTs in
      muscle and liver, and ethoxyresorufin O-deethylase (EROD) activity were measured
      at day 0, 21, 120 and 270. In specimens captured in the estuary total PCB and
      total DDT concentrations were 311 and 65 ng g(-1) in muscle and 686 and 115 ng g(
      1) in liver, respectively. At day 21, after an initial 10-15 days period of
      starvation, organochlorines levels increased in both analyzed tissues. Thereafter
      levels of all PCB congeners and DDT compounds decreased in muscle, and at the end
      of the 270 days were 49 ng g(-1) and 13 ng g(-1), respectively. These decreases
      were correlated to the lipids consumption. In liver no relationship between those
      variables was observed, suggesting different elimination processes and eventual
      exchange of contaminants between muscle and liver. EROD activities decreased in
      the first days of depuration experiment, but showed no relations with analysed
      organochlorines.

PMID- 17207837
TI  - Towards an Intergovernmental Panel on Chemical Pollution (IPCP).

PMID- 17207838
TI  - Chromium accumulation by the hyperaccumulator plant Leersia hexandra Swartz.
AB  - Leersia hexandra Swartz (Gramineae), which occurs in Southern China, has been
      found to be a new chromium hyperaccumulator by means of field survey and pot
      culture experiment. The field survey showed that this species had an
      extraordinary accumulation capacity for chromium. The maximum Cr concentration in
      the dry leaf matter was 2978 mg kg(-1) on the side of a pond near an
      electroplating factory. The average concentration of chromium in the leaves was
      18.86 times as that in the pond sediment, and 297.41 times as that in the pond
      water. Under conditions of the nutrient solution culture, it was found that L.
      hexandra had a high tolerance and accumulation capacity to Cr(III) and Cr(VI).
      Under 60 mg l(-1) Cr(III) and 10 mg l(-1) Cr(VI) treatment, there was no
      significant decrease of biomass in the leaves of L. hexandra (p>0.05). The
      highest bioaccumulation coefficients of the leaves for Cr(III) and Cr(VI) were
      486.8 and 72.1, respectively. However, L. hexandra had a higher accumulation
      capacity for Cr(III) than for Cr(VI). At the Cr(III) concentration of 10 mg l(-1)
      in the culture solution, the concentration of chromium in leaves was 4868 mg kg(
      1), while at the same Cr(VI) concentration, the concentration of chromium in
      leaves was only 597 mg kg(-1). These results confirmed that L. hexandra is a
      chromium hyperaccumulator which grows rapidly with a great tolerance to Cr and
      broad ecological amplitude. This species could provide a new plant resource that
      explores the mechanism of Cr hyperaccumulation, and has potential for usage in
      the phytoremediation of Cr-contaminated soil and water.

PMID- 17207839
TI  - Anammox enrichment from different conventional sludges.
AB  - Three sets of sequencing batch reactor (SBR) were used for Anammox enrichment
      from conventional sludges including upflow anaerobic sludge blanket, activated
      sludge, and anaerobic digestion sludge. After four months of operation, the
      Anammox activity occurred in all reactors allowing continuous removal of ammonium
      and nitrite. The morphology of the cultivated Anammox sludge was observed using
      scanning electron microscope. The photographs showed that the obtained culture
      was mostly spherical in shape, presumably Anammox culture. There were also
      filamentous-like bacteria co-existing in the system. Fluorescence in situ
      hybridization (FISH) analysis using 16S rRNA targeting oligonucleotide probes
      PLA46 and Amx820 showed that the dominant population developed in all SBRs was
      hybridized with both PLA46 and Amx820 gene probes. It means that the cultivated
      biomass in all SBRs was classified in the group of Planctomycetales bacteria with
      respect to the anaerobic ammonium-oxidizing bacteria, Candidatus Brocadia
      anammoxidans and Candidatus Kuenenia stuttgartiensis. Numerous time sequences
      were tested in this experiment. The shortest workable reaction time was found in
      the range from 5 to 7 h. Good quiescence of sludge was obtained at 30 min of
      settle period followed by a discharge period of 15 min. A long-term performance
      showed a near perfect removal of nitrite based on the influent NO2(-)-N
      concentration of 50-70 mg l(-1). The maximum ammonia removal efficiency was 80%
      with the influent NH4(+)-N concentration of 40-60 mg l(-1). It is, therefore,
      concluded that Anammox cultivation from conventional sludges was highly possible
      under control environment within four months.

PMID- 17207840
TI  - The input-output balance of cadmium in a paddy field of Tokyo.
AB  - Field monitoring was practiced from 2001 to 2003 to evaluate the input
      (irrigation, atmospheric deposition, and fertilizer application) and the output
      (uptake and accumulation into the above-ground biomass of rice plants and
      leaching) of cadmium (Cd) in a contaminated paddy field in Tokyo. The cadmium
      concentrations of irrigated water, open-bulk precipitation, soil solution
      (leaching water), rice plants collected at the harvesting stage and the chemical
      fertilizer and the cow manure compost applied were determined. The Cd flux of
      each factor was calculated by multiplying the Cd concentration by the volume or
      mass of the media. The annual input-output balance of Cd in the paddy field in
      2001 and 2002 was estimated to be -5.44 [corrected] g ha(-1) and -2.01
      [corrected] g ha(-1), respectively, indicating the loss of Cd from the paddy
      field, although the losses accounted for only 0.24% [corrected] and 0.089%
      [corrected] of the total amount of Cd in the ploughed layer soil in 2001 and
      2002, respectively. Among the factors involved, the input from fertilizers
      (including manure compost) and the output due to the uptake by rice plants played
      a major role in the balance. The former largely depended on the types and amounts
      of fertilizers applied, and the latter on the water management practices in the
      paddy field, such as flooding and drainage of the surface water.

PMID- 17207841
TI  - Concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl
      ethers (PBDEs) in milk of women from Catalonia, Spain.
AB  - In this study, the concentrations of polychlorinated biphenyls (PCBs) and
      polybrominated diphenyl ethers (PBDEs) in milk from women living in the vicinity
      of a new hazardous waste incinerator (HWI) in Catalonia, Spain, were determined.
      The study was performed after 4 years of regular operations in the facility and
      the present PCB levels were compared with baseline concentrations obtained in a
      pre-operational program. PCBs and PBDEs levels were determined by HRGC/HRMS in 15
      samples. In the present study planar PCBs ranged from 1.3 to 6.3 pg WHO-TEQ/g fat
      with a mean value of 3.8 pg WHO-TEQ/g fat. After adding dioxin-like mono-ortho
      PCBs the total PCB-TEQ concentrations ranged from 3.8 to 13.3 pg WHO-TEQ/g fat
      (mean value: 8.7 pg WHO-TEQ/g fat). A comparison of the current data with those
      obtained in the baseline study showed significant decreases for both planar and
      total WHO-TEQ of PCBs: 47.9% and 44.6%, respectively. PCB concentrations in milk
      of women living in urban zones were higher than those living near industrial
      areas (10.1 and 7.4 pg WHO-TEQ/g fat, respectively). Mean PBDE concentrations
      were 2.2 and 2.5 ng/g fat for women living in urban and industrial zones,
      respectively. Dietary intake of PCBs and PBDEs for a standard adult woman samples
      were 898 and 843 ng/day for PCBs, and 72 and 63 ng/day for PBDEs, for residents
      in urban and industrials areas, respectively. This study suggests that dietary
      intake is more relevant for human exposure to PCBs and PBDEs than living near the
      HWI.

PMID- 17207842
TI  - Refinements on the age-dependent half-life model for estimating child body
      burdens of polychlorodibenzodioxins and dibenzofurans.
AB  - We modified our prior age-dependent half-life model to characterize the range of
      child (ages 0-7) body burdens associated with dietary and environmental exposure
      to polychlorodibenzodioxins and furans (PCDD/Fs). Several exposure scenarios were
      evaluated. Infants were assumed to be either breast-fed or formula-fed from birth
      to 6 months of age. They then received intakes of PCDD/Fs through age 7 from
      foods based on weighted means estimates [JECFA, 2001. Joint FAO/WHO Committee on
      Food Additives. Fifty-seventh meeting, Rome, June 5-14 , 2001, pp. 24-40], and
      with or without exposures (ingestion and dermal) to urban residential soils at
      1ppb TCDD toxic equivalents (TEQ). A one-compartment (adipose volume)
      toxicokinetic model for TCDD described by Kreuzer [Kreuzer, P.F., Csanady, Gy.A.,
      et al., 1997. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and congeners in
      infants. A toxicokinetic model of human lifetime body burden by TCDD with special
      emphasis on its uptake by nutrition. Arch. Toxicol. 71, 383-400] was expanded to
      include the key non-TCDD congeners in human breast milk and adipose tissues, and
      two model parameter refinements were examined: (1) use of updated and more
      detailed age-correlated body fat mass data [CDC, 2000. Centers for Disease
      Control. CDC Growth Charts: United States. Advance Data from Vital and Health
      Statistics of the Centers for Disease Control and Prevention, National Center for
      Health Statistics, Number 314, December 2000]; (2) use of breast milk PCDD/F
      concentration data from sampling completed in 2000-2003 [Wittsiepe, J., Furst,
      P., et al., 2004. PCDD/F and dioxin-like PCB in human blood and milk from German
      mothers. Organohalogen Compd. 66, 2865-2872]. The updated body fat mass data
      nearly halved the predicted peak body burden for breast-feeding and lowered the
      time-weighted average (TWA) body burdens from ages 0-7 by 30-40% for breast-fed
      and formula-fed infants. Combined use of the updated breast milk PCDD/F
      concentration and body fat mass data increased the contribution of breast-feeding
      but reduced TWA body burdens from diet and soil. We conclude that further
      refinements are needed, but reliance on these better data sets for body fat mass
      and breast milk PCDD/F concentration significantly improves the model's ability
      to accurately predict body burdens during early childhood.

PMID- 17207843
TI  - Levels of PCDDs, PCDFs, and PCBs in the blood of the non-occupationally exposed
      residents living in the vicinity of a chemical plant in the Czech Republic.
AB  - In 2003, concentrations of altogether 17 PCDD/Fs congeners and 12 non-ortho and
      mono-ortho dioxin-like PCBs were measured in the blood of 60 randomly selected
      adults who lived in three settlements surrounding a chemical plant that had been
      producing chlorinated herbicides (mainly HCHs, HCB, pentachlorophenole, 2,4,5-T)
      in the 1960's; subjects consuming home-produced animal foods were chosen. Twenty
      blood donors with similar characteristics from the locality with about 80 km
      distance were used as control subjects. The factors that influenced the dioxin
      levels were investigated on the basis of a questionnaire. The aim of our study
      was to find out whether the residents living in the surroundings of the chemical
      plant are at a greater exposure risk than the controls. To calculate TEQ values,
      WHO-TEFs were used. The concentrations of four PCDD and six PCDF congeners were
      below the LOD in more than 50% of samples. Significantly higher WHO-TEQ levels
      (p<0.05) were found for PCDDs, PCDFs, or PCBs in all three followed up groups
      compared with controls. The geometric means of the total TEQ values for
      PCDD/F/PCBs were 43.8, 50.2, and 40.0 pg/g fat compared to 23.2 pg/g fat in the
      control. The percentages of TEQ due to the measured congeners in exposed groups
      were 9-10.3% for PCDDs, 20.5-26.9% for PCDFs, 19.2-23.1% for coplanar and 43.6
      47.2% for mono-ortho PCBs. In control, the percentage of TEQ was 11.6, 26.7,
      24.1, and 37.5%. PCBs, predominantly PCB156, followed by PCB126 contributed 60 to
      70% of the total TEQ value. Positive correlation of the PCDD/PCDF/PCB blood
      levels with age and with consumption of locally produced eggs was found.

PMID- 17207844
TI  - Characterisation of polymer fractions from waste electrical and electronic
      equipment (WEEE) and implications for waste management.
AB  - There is an increasing interest in the end-of-life management of polymers present
      in waste electrical and electronic equipment (WEEE). This is mainly due to high
      recycling and recovery quotas set by the European WEEE directive, which can only
      be fulfilled by including the plastic fraction in recycling and recovery
      approaches. Previous studies identified a high material diversity and various
      contaminants in WEEE plastics, including heavy metals, polybrominated biphenyls
      (PBB), diphenyl ethers (PBDE), as well as polybrominated dibenzodioxins and
      dibenzofurans (PBDD/F). These substances are regulated by European directives
      that limit their levels in marketable products. Consequently, both material
      diversity and contaminants are strong arguments against material recycling and
      point to hazardous waste treatment. However, recent developments in the
      production of flame retardants and electrical and electronic goods aimed to
      reduce contaminants and material diversity. Thus, the present study summarises
      updated contaminant levels of plastic fractions of European WEEE, as well as data
      on materials in waste housing polymers. Material characterisation revealed
      housing fractions to be interesting sources for polymer recycling, which however
      has to implement potent material separation and/or bromine elimination
      techniques. With respect to contaminants, our data indicate an effective phase
      out of PBB, but still high levels of PBDE and PBDD/F are found. Sources and
      implications for the material recycling and thermal recovery approaches are
      discussed in detail.

PMID- 17207845
TI  - Co-variations of bacterial composition and catabolic genes related to PAH
      degradation in a produced water treatment system consisting of successive anoxic
      and aerobic units.
AB  - This paper reports on the investigation of concentration levels of PAHs,
      community structure, as well as the abundance of PAH-related catabolic genes
      including upper-pathway dioxygenase genes (nahAc and phnAc) and down-pathway
      catechol dioxygenase genes (C12O and C23O) in a successive anoxic and aerobic
      treatment of produced water from the Jidong Oilfield, China. 93% of total PAHs
      were removed, almost equally contributed by the anoxic and aerobic units.
      However, PAHs of more than 3 benzene rings remained almost unchanged. The signals
      for phnAc and C12O were undetectable in this biological system, whereas the
      existence of nahAc and C23O was confirmed in the system and the copies of the two
      genes in the aerobic tank were 2 or 3 orders higher than those in the influent
      water sample. The different behavior of C23O demonstrated that mineralization of
      PAHs might mainly occur in the aerobic unit. The existence of nahAc and C23O
      genes in the influent and the high similarity of genotype between the influent
      and the two sludge samples suggested that bacteria existing in the influent
      contributed to PAH removal and bacteria harboring PAH catabolic genes were
      enriched in the sludge.

PMID- 17207846
TI  - Hydrogeochemical characteristics of the Tinto and Odiel Rivers (SW Spain).
      Factors controlling metal contents.
AB  - The Tinto and Odiel Rivers are strongly affected by acid mine drainage (AMD) due
      to the intense sulphide mining developed in their basins over the past 5000
      years. In this study the results obtained from a weekly sampling in both rivers,
      before their mouth in the Ria of Huelva, over three and a half years of control
      are analysed. In the Tinto River, the concentrations of sulphates, Al, Cd, Co, Li
      and Zn are double to those of the Odiel as a consequence of lower dilution.
      However, the concentration of Fe in the Odiel River is 20 times lower, since the
      precipitation of Fe oxyhydroxysulphates caused by neutralisation processes is
      more intense. Lower As, Cr, Cu and Pb concentrations are also found in the Odiel
      River as, to a greater or lesser extent, they are sorbed and/or coprecipitated
      with Fe. Other elements such as Be, Mn, Ni and Mg show similar values in both
      systems, which is ascribed to lithological factors. The seasonal evolution of
      contaminants is typical of rivers affected by AMD, reaching a maximum in autumn
      due to the dissolution of evaporitic salts precipitated during the summer.
      Nevertheless, in the Tinto River, Ca, Na and Sr show a strong increase during the
      summer, probably due to a greater water interaction with marly materials, through
      which the last reach of the river flows. Barium has a different behaviour from
      the rest of the metals and its concentration seems to be controlled by the
      solubility of barite. Iron, As and Pb show different behaviours in both rivers,
      those for Fe and As possibly linked to the prevalence of different dissolved
      species of Fe. The different Pb pattern is probably due to the control of Pb
      solubility by anglesite or other minerals rich in Pb in the Tinto River.

PMID- 17207847
TI  - Air quality assessment for Portugal.
AB  - According to the Air Quality Framework Directive, air pollutant concentration
      levels have to be assessed and reported annually by each European Union member
      state, taking into consideration European air quality standards. Plans and
      programmes should be implemented in zones and agglomerations where pollutant
      concentrations exceed the limit and target values. The main objective of this
      study is to perform a long-term air quality simulation for Portugal, using the
      CHIMERE chemistry-transport model, applied over Portugal, for the year 2001. The
      model performance was evaluated by comparing its results to air quality data from
      the regional monitoring networks and to data from a diffusive sampling
      experimental campaign. The results obtained show a modelling system able to
      reproduce the pollutant concentrations' temporal evolution and spatial
      distribution observed at the regional networks of air quality monitoring. As far
      as the fulfilment of the air quality targets is concerned, there are excessive
      values for nitrogen and sulfur dioxides, ozone also being a critical gaseous
      pollutant in what concerns hourly concentrations and AOT40 (Accumulated Over
      Threshold 40 ppb) values.

PMID- 17207848
TI  - An asset-based community initiative to reduce television viewing in New York
      state.
AB  - BACKGROUND: Childhood obesity is an epidemic. Addressing this problem will
      require the input of many sectors and change in many behaviors. The "community"
      must be part of the solution, and the solution must be constructed on existing
      assets that lend strength to positive environmental change. OBJECTIVE: To
      catalyze an established asset-based community partnership to support efforts to
      reduce television viewing time by developing and providing alternative activities
      as part of a broader, 3-year study to reduce childhood obesity among preschool
      aged children in rural, upstate New York. METHOD: Asset mapping was utilized to
      compile an inventory of individual and community strengths upon which a
      partnership could be established. Facilitated focus group sessions were conducted
      to better understand childcare environmental policies and practices, and to guide
      changes conducive to health and fitness. Planning meetings and targeted outreach
      brought key stakeholders together for a community-participatory initiative to
      support positive environmental change. RESULTS.: The partnership planned and
      initiated an array of after-school and weekend community activities for preschool
      aged children and their families in the weeks preceding, during, and following a
      designated 'TV Turn-off' week in April, 2004 and March, 2005. CONCLUSION: Methods
      of asset-based community development are an effective way to engage community
      participation in public health initiatives.

PMID- 17207849
TI  - Alprazolam induced conformational change in hemoglobin.
AB  - Alprazolam (ALP) is a widely prescribed sedative and antidepressant
      benzodiazepine group of drugs. The wide uses of this drug lead us to investigate
      its possible interaction with hemoglobin (Hb). Spectrophotometric and
      spectofluorimetric studies showed strong binding of ALP with Hb. Circular
      dichroic spectra showed that alpha-helical structure of Hb-subunits has been
      largely changed. On ALP treatment partial pressure of O(2) is increased in the
      blood indicating release of O(2) from erythrocytes. Further, the binding of ALP
      induced conformational changes in Hb resulting in larger Hb particle size was
      demonstrated by dynamic light scattering experiment. Thus, the present study
      unambiguously raises question of danger of random usage of ALP, which binds with
      and changes the function of Hb.

PMID- 17207850
TI  - Biosynthesis and native granule characteristics of poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) in Delftia acidovorans.
AB  - The ability of Delftia acidovorans to incorporate a broad range of 3
      hydroxyvalerate (3HV) monomers into polyhydroxyalkanoate (PHA) copolymers was
      evaluated in this study. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co
      3HV)] containing 0-90 mol% of 3HV was obtained when a mixture of sodium 3
      hydroxybutyrate and sodium valerate was used as the carbon sources. Transmission
      electron microscopy analysis revealed an interesting aspect of the P(3HB-co-3HV)
      granules containing high molar ratios of 3HV whereby, the copolymer granules were
      generally larger than those of poly(3-hydroxybutyrate) [P(3HB)] granules, despite
      having almost the same cellular PHA contents. The large number of P(3HB-co-3HV)
      granules occupying almost the entire cell volume did not correspond to a higher
      amount of polymer by weight. This indicated that the granules of P(3HB-co-3HV)
      contain polymer chains that are loosely packed and therefore have lower density
      than P(3HB) granules. It was also interesting to note that a decrease in the
      length of the side chain from 3HV to 4-hydroxybutyrate (4HB) corresponded to an
      increase in the density of the respective PHA granules. The presence of longer
      side chain monomers (3HV) in the PHA structure seem to exhibit steric effects
      that prevent the polymer chains in the granules from being closely packed. The
      results reported here have important implications on the maximum ability of
      bacterial cells to accumulate PHA containing monomers with longer side chain
      length.

PMID- 17207851
TI  - Role of green tea polyphenols in the inhibition of collagenolytic activity by
      collagenase.
AB  - Inhibitory effect of green tea polyphenols viz., catechin and epigallocatechin
      gallate (EGCG) on the action of collagenase against collagen has been probed in
      this study. Catechin and EGCG treated collagen exhibited 56 and 95% resistance,
      respectively, against collagenolytic hydrolysis by collagenase. Whereas direct
      interaction of catechin and EGCG with collagenase exhibited 70 and 88%
      inhibition, respectively, to collagenolytic activity of collagenase against
      collagen and the inhibition was found to be concentration dependent. The kinetics
      of inhibition of collagenase by catechin and EGCG has been deduced from the
      extent of hydrolysis of (2-furanacryloyl-L-leucyl-glycyl-L-prolyl-L-alanine),
      FALGPA. Both catechin and EGCG exhibited competitive mode of inhibition against
      collagenase. The change in the secondary structure of collagenase on treatment
      with catechin and EGCG has been monitored using circular dichroism
      spectropolarimeter. CD spectral studies showed significant changes in the
      secondary structure of collagenase on treatment with higher concentration of
      catechin and EGCG. Higher inhibition of EGCG compared to catechin has been
      attributed to the ability of EGCG to exhibit better hydrogen bonding and
      hydrophobic interaction with collagenase.

PMID- 17207852
TI  - Partial characterization of giant extracellular hemoglobin of Glossoscolex
      paulistus: a MALDI-TOF-MS study.
AB  - In this work, MALDI-TOF-MS analysis was performed to obtain information on the
      molecular mass of the different subunits from the giant extracellular hemoglobin
      of Glossoscolex paulistus (HbGp) in the oxy-form. Experiments were performed for
      the whole protein at pH 7.0, for the partially dissociated protein at pH 9.0, and
      for the fraction obtained from gel filtration in Sephadex G-200, at pH 9.0,
      corresponding to the isolated monomer d. Besides that, experiments were performed
      for the whole protein treated with 2-mercaptoethanol in order to monitor the
      effects of reduction of the disulfide bonds, which are expected to maintain the
      trimer (abc) in the native molecule. The results are compared to those reported
      for the homologous hemoglobin of Lumbricus terrestris (HbLt) and some tentative
      assignments are made for the observed polypeptides. The monomer d is found to
      exist in, at least, two major forms of identical proportions with masses of
      16,355+/-25 and 16,428+/-24 Da, respectively. Two minor forms were also observed
      around 16 kDa for the monomers. Upon disulfide bonds reduction the peak
      associated to the trimer is absent in the mass spectrum, and new peaks assigned
      tentatively to the monomers a, b and c on the basis of comparison with Lumbricus
      terrestris hemoglobin literature data are observed. Their molecular masses were
      18,258+/-30, 16,492+/-24 and 17,363+/-17 Da, respectively. Two linker chains for
      HbGp were also observed at 25,817+/-50 and 26,761+/-16 Da, and this result is
      different from HbLt, where four linker chains were reported in the range 24-32
      kDa. Finally, trimers (abc) were observed at 51-52 kDa. This partial
      characterization, performed for the first time, is an important step in the
      characterization of subunits of this giant extracellular hemoglobin.

PMID- 17207853
TI  - Childhood neglect and adulthood involvement in HIV-related risk behaviors.
AB  - OBJECTIVE: Much research has been done to examine the long-term effects of being
      victimized by sexual, physical, and/or emotional abuse in childhood, but much
      less research has focused on the impact of childhood neglect experiences. This
      study examines the role that childhood neglect has on adult women's involvement
      in HIV-related risky behaviors. METHODS: The data come from a study of 250 "at
      risk" women living in the Atlanta, GA metropolitan area, most of whom were
      African American. Data were collected in face-to-face interviews between 1997 and
      2000. Multiple regression was used to explore the relationship between childhood
      neglect experiences, self-esteem, attitudes toward condom use, and involvement in
      HIV-related risky behaviors. RESULTS: Overall, the model tested received strong
      support by the study data. Childhood neglect led to reduced self-esteem. Neglect
      was associated with worsened attitudes toward condom use and women who
      experienced childhood neglect also reported more involvement in HIV risk
      behaviors. CONCLUSIONS: HIV intervention programs ought to target women who have
      experienced childhood neglect, as neglect experiences have adverse impacts upon
      their self-esteem, condom-related attitudes, and HIV risk behavior practices in
      adulthood.

PMID- 17207854
TI  - Lamotrigine poisoning presenting as seizures: a case of deliberate poisoning.
AB  - Features of Lamotrigine poisoning are not clearly described in children. We
      report a child who presented with seizures and bizarre neurological symptoms,
      later attributed to lamotrigine poisoning.

PMID- 17207855
TI  - Broad host range fluorescence and bioluminescence expression vectors for Gram
      negative bacteria.
AB  - Tagging of bacteria with living colors and living light allows increasingly
      valuable new imaging and detection technologies to be accessible to researchers.
      In this study, we aimed to create stable broad host range expression vectors for
      tagging Gram-negative bacteria with fluorescence and bioluminescence. To
      accomplish this, a mutated form of promoterless green fluorescent protein (gfp)
      gene, gfpmut3a, from Aequorea victoria and promoterless bacterial luciferase
      genes, luxCDABE, from Photorhabdus luminescens were inserted into broad host
      range plasmid pBBR1MCS4. Expression of gfp and luxCDABE genes was driven by lacZ
      promoter. In addition, dual versions with both gfpmut3a and luxCDABE genes and
      inducible versions carrying lacI(q) gene were also constructed. These new broad
      host range vectors containing a stable broad host range origin of replication and
      mobility genes can be transferred to Gram-negative bacteria by either
      electroporation or conjugal mating and maintained stably. Availability of these
      expression vectors should be useful in developing new approaches to study a broad
      variety of Gram-negative bacteria, particularly for applications investigating
      host-pathogen interactions in vivo and in vitro.

PMID- 17207856
TI  - Btk regulates multiple stages in the development and survival of B-1 cells.
AB  - B-1 cells are important players in the first line of defense against pathogens.
      According to current models for the origin of B-1 cells, they either represent a
      separate lineage from conventional B-2 cells or differentiate from conventional B
      2 cells via an intermediate, B-1(int), in response to positive selection by
      antigen. Here we show that Btk, a Tec family kinase that mediates B cell antigen
      receptor (BCR) signaling, is required at multiple stages of B-1 cell development.
      VH12 anti-phosphatidylcholine (PtC) IgH transgenic mice provide a model for the
      induced differentiation of B-1 cells. This transgene selects for PtC-reactive
      cells and induces them to adopt a B-1 phenotype. Both processes have been shown
      to depend on Btk. To determine whether this is secondary to a requirement for Btk
      in the development of mature B-2 cells, we crossed VH12 transgenic mice to mice
      expressing low levels of Btk. B-2 cell development occurs normally in Btk(lo)
      mice despite reduced responsiveness to BCR crosslinking. Analysis of VH12.Btk(lo)
      mice reveals that Btk regulates the B-1(int) to B-1 transition and/or the
      survival of splenic B-1 cells, in part via a mechanism independent of its role in
      BCR signaling. We also show that Btk mediates the survival of, and expression of
      IL-10 by, those B-1 cells that do develop and migrate to the peritoneum. Multiple
      roles for Btk in B-1 cell development and maintenance may explain the particular
      sensitivity of this population to mutations in components of Btk signaling
      pathways.

PMID- 17207857
TI  - Constant mitochondrial DNA levels in blood leukocytes of patients enrolled in a
      NRTI-free therapeutic trial (BIKS-2 study).
AB  - OBJECTIVES: Determine if a nucleoside reverse transcriptase inhibitors (NRTI)
      free regimen affected mitochondrial DNA (mtDNA) levels in peripheral blood
      mononuclear cells (PBMCs) of patients enrolled in BIKS-2 trial. METHODS:
      Antiretroviral (ARV) naive (N=13) and NRTI experienced (N=7) patients, received
      lopinavir/ritonavir, a boosted protease inhibitor, and efavirenz, a non
      nucleoside reverse transcriptase inhibitor from Month (M) 0 to M12 (1-year BIKS
      trial) and from M12 to M36 (2-year BIKS-2 trial). MtDNA was quantified at M12,
      M24 and M36 via real-time PCR assay. RESULTS: From M12 to M36, the 20 patients
      have maintained undetectable plasma HIV-1 RNA, gained CD4 cells and had no side
      effects attributable to these drugs. Median mtDNA contents were constant: 478.6
      at M12, 478.6 at M24 and 324.4 copies/cell at M36 (pM12-M36=0.5). Because M0 data
      is missing, these results were compared to those of two groups of age matched
      individuals: healthy donors and HIV-infected patients before and after exposure
      to NRTIs. Healthy donors have higher contents (871), followed by patients never
      treated (602), than by BIKS patients where 7 had toxic NRTIs (478.6) and at last
      by patients exposed for six months to the most toxic combination (ddI-d4T) (85
      copies/cell). CONCLUSION: Lopinavir/ritonavir+efavirenz did not affect mtDNA
      contents in PBMCs.

PMID- 17207858
TI  - Eosinophilic pneumonia induced by daptomycin.
AB  - We present a case of drug-induced eosinophilic pneumonia resulting from
      intravenous daptomycin being used as therapy for recurrent methicillin-sensitive
      Staphlococcus aureus endocarditis. The patient developed hypoxic respiratory
      failure requiring intubation and mechanical ventilation. Daptomycin therapy was
      discontinued immediately, and the patient improved significantly after the
      administration of intravenous corticosteroids allowing for extubation 3 days
      later.

PMID- 17207859
TI  - Mycobacterium marinum as a cause of chronic granulomatous tenosynovitis in the
      hand.
AB  - OBJECTIVE: Mycobacterium marinum is an uncommon cause of chronic granulomatous
      flexor tenosynovitis and leads to significant morbidity in the hand. This paper
      aims to review our treatment of this infection and its clinical outcomes.
      METHODS: We treated five cases of M. marinum flexor tenosynovitis from 2001 to
      2006, which were confirmed after 6 weeks of mycobacterial culture. RESULTS: All
      the patients were healthy immuno-competent hosts. There was a history of injury
      by a marine animal in each patient. Presentation was delayed at an average of
      32.0 days after the injury. Excisional debridement was performed at an average of
      63.4 days after the injury. The average number of debridements performed was 3.4.
      One patient had to undergo ray amputation to control the infection. The average
      duration of oral antibiotics was 15.4 weeks. Post-operatively, there were
      reductions in total active motion in all patients. CONCLUSION: A high index of
      suspicion, based on the history and intra-operative findings, is necessary when
      managing these patients. This infection runs a protracted course that requires
      multiple debridements and is associated with poor functional outcome.

PMID- 17207860
TI  - Procoagulant and fibrinolytic activity in cerebrospinal fluid from adults with
      bacterial meningitis.
AB  - OBJECTIVES: This study investigated levels of coagulation and fibrinolysis
      factors in cerebrospinal fluid (CSF) from adults with bacterial meningitis in
      relation to development of brain infarction. METHODS: CSF was collected from 92
      adults with community-acquired bacterial meningitis, who participated in the
      prospective Dutch Meningitis Cohort Study; 8 patients with viral meningitis and 9
      healthy control subjects. Levels of proteins involved in the coagulation cascade
      were determined by means of immunoassays. RESULTS: Bacterial meningitis was
      accompanied by local activation of coagulation, as shown by significantly higher
      CSF soluble tissue factor (P<0.001) and prothrombin fragment F1+2 concentrations
      (P<0.001) as compared to viral meningitis patients and controls. This was
      accompanied by a significantly higher D-dimer formation (P<0.001). In addition,
      in bacterial meningitis fibrinolysis was attenuated, since CSF plasminogen
      activator inhibitor (PAI)-1 levels were significantly higher as compared to the
      controls (P=0.02). In patients with bacterial meningitis who developed brain
      infarction, CSF PAI-1 levels were higher than in those without infarction
      (P=0.04). CONCLUSIONS: Activation of coagulation and attenuation of fibrinolysis
      in the CSF are important features of bacterial meningitis; the net effect on
      fibrin turnover may contribute to the development of brain infarction.

PMID- 17207861
TI  - Comparative analysis of in vitro conditions for rat adult neural progenitor
      cells.
AB  - Various protocols have been published for in vitro expansion and maintenance of
      adult neural progenitor cells (ANPC). However, there are only few data comparing
      these protocols regarding their influence on proliferation, migration and
      differentiation. Freshly isolated ANPC from olfactory bulb (BO) and dentate gyrus
      (DG) of adult rat brains forming neurospheres and expressing the neural stem cell
      markers nestin and Sox-2 were used in a comparative analysis of five different
      medium combinations. Medium containing N2 and fetal calf serum (FCS), but no
      additional cytokines was unsuitable for an effective long-term expansion of ANPC
      due to a significantly reduced proliferation rate. Media containing BIT, basic
      fibroblast growth factor (bFGF), epidermal growth factor (EGF), platelet-derived
      growth factor AB (PDGF-AB) and leukemia inhibitory factor (LIF) or B27, bFGF and
      EGF are recommendable for the cultivation of DG-derived ANPC as neurospheres
      only. Unlike, culture media containing BIT, bFGF, EGF and PDGF-AB or N2, bFGF and
      EGF were suitable for all applications tested as they responded similarly
      regarding proliferation, migration and expression of differentiation markers. The
      results of the present study might help to improve the effective in vitro
      expansion of ANPC derived from rare human tissue samples.

PMID- 17207862
TI  - An automated tracking system for Caenorhabditis elegans locomotor behavior and
      circadian studies application.
AB  - Automation of simple behavioral patterns, such as locomotor activity, is
      fundamental for pharmacological and genetic screening studies. Recently,
      circadian behaviors in locomotor activity and stress responses were reported in
      the nematode Caenorhabditis elegans, a well-known model in genetics and
      developmental studies. Here we present a new method for long-term recordings of
      C. elegans (as well as other similar-sized animals) locomotor activity based on
      an infrared microbeam scattering. Individual nematodes were cultured in a 96-well
      microtiter plate; we tested L15, CeMM and E. coli liquid cultures in long-term
      activity tracking experiments, and found CeMM to be the optimal medium. Treatment
      with 0.2% azide caused an immediate decrease in locomotor activity as recorded
      with our system. In addition to the validation of the method (including hardware
      and software details), we report its application in chronobiological studies.
      Circadian rhythms in animals entrained to light-dark and constant dark conditions
      (n=48 and 96 worms, respectively) at 16 degrees C, were analyzed by LS
      periodograms. We obtained a 24.2+/-0.44 h period (52% of significantly rhythmic
      animals) in LD, and a 23.1+/-0.40 h period (37.5% of significantly rhythmic
      animals) under DD. The system is automateable using microcontrollers, of low-cost
      construction and highly reproducible.

PMID- 17207863
TI  - Anxiogenic-like effects of mCPP microinfusions into the amygdala (but not dorsal
      or ventral hippocampus) in mice exposed to elevated plus-maze.
AB  - Serotonin (5-HT) can either increase or decrease anxiety-like behaviour in
      animals, actions that depend upon neuroanatomical site of action and 5-HT
      receptor subtype. Although systemic studies with 5-HT(2) receptor agonists and
      antagonists suggest a facilitatory role for this receptor subtype in anxiety,
      somewhat inconsistent results have been obtained when such compounds have been
      directly applied to limbic targets such as the hippocampus and amygdala. The
      present study investigated the effects of the 5-HT(2B/2C) receptor agonist mCPP
      bilaterally microinjected into the dorsal hippocampus (DH: 0, 0.3, 1.0 or
      3.0nmol/0.2microl), the ventral hippocampus (VH: 0, 0.3, 1.0 or
      3.0nmol/0.2microl) or the amygdaloid complex (0, 0.15, 0.5, 1.0 or
      3.0nmol/0.1microl) in mice exposed to the elevated plus-maze (EPM). Test sessions
      were videotaped and subsequently scored for conventional indices of anxiety
      (percentage of open arm entries and percentage of open arm time) and locomotor
      activity (closed arm entries). Results showed that mCPP microinfusions into the
      DH or VH failed to affect any behavioural measure in the EPM. However, when
      injected into the amygdaloid complex, the dose of 1.0nmol of this 5HT(2B/2C)
      receptor agonist increased behavioural indices of anxiety without significantly
      altering general activity levels. This anxiogenic-like effect of mCPP was
      selectively and completely blocked by local injection of a behaviourally-inactive
      dose of SDZ SER-082 (10nmol/0.1microl), a preferential 5-HT(2C) receptor
      antagonist. These data suggest that 5HT(2C) receptors located within the
      amygdaloid complex (but not the dorsal or ventral hippocampus) play a
      facilitatory role in plus-maze anxiety in mice.

PMID- 17207864
TI  - Brain ECF antioxidant interactions in hamsters during arousal from hibernation.
AB  - Warming from hibernation to cenothermia involves intense metabolic activity and
      large fluxes in regional blood flow and volume. During this transition, levels of
      the antioxidants, ascorbate (AA), urate and glutathione (GSH) in brain tissue,
      extracellular fluid (ECF) and plasma change substantially. Striatal ECF was
      sampled and manipulated using very slow perfusion microdialysis to examine the
      mechanisms that influence the changing profile of striatal ECF AA, urate and GSH
      levels during arousal from hibernation to cenothermia in Syrian hamsters
      (Mesocricetus auratus). Omission of glucose from the perfusate had no effect upon
      the respective decrease, increase and transient increase in striatal ECF levels
      of AA, GSH and urate observed during arousal from hibernation to cenothermia. In
      contrast, inhibition of xanthine dehydrogenase/oxidase (XOR) activity by reverse
      dialysis with oxypurinol, itself a free radical scavenger, decreased ECF urate
      and preserved ECF AA levels. This suggests that some ECF AA is oxidized by free
      radical products of XOR flux and/or by other free radical producing processes
      activated during the transition from hibernation to cenothermia. Local
      supplementation of ECF AA, GSH and cystiene had no effect upon the profile of
      transient increase of ECF urate observed during arousal from hibernation. The
      production of free radicals by XOR and the disappearance of AA from the ECF
      continues for at least 2h immediately after the hamster has attained cenothermia.
      The hamster, immediately after arousal from hibernation, can be utilized as a
      natural model to study free radical production and effective scavenging at
      cenothermia.

PMID- 17207865
TI  - Further study of the effects of dopaminergic D1 drugs on place avoidance behavior
      using pretraining: some negative evidence.
AB  - Dopaminergic neurotransmission is considered to modulate cognitive processes,
      including spatial memory. The aim of this study was to further evaluate the role
      of the D1 receptor system in an active allothetic place avoidance (AAPA) task
      using pretrained rats. Our previous results showed enhanced AAPA learning after
      systemic injections of low doses of D1 agonist A77636, and the impairment of AAPA
      acquisition by D1 blocker SCH23390 [Stuchlik A, Vales K. Effect of dopamine D1
      receptor antagonist SCH23390 and agonist A77636 on active allothetic place
      avoidance, a spatial cognition task. Behav Brain Res 2006;172(2):250-255]. In the
      present study, we used the intact-pretraining paradigm, in which animals were
      trained to the task prior to the injections and subsequently retrieval and
      reacquisition of AAPA while under the effects of the drugs was tested. Results
      showed that the intact pretraining partly eliminated the effects of A77636 and
      SCH23390 on AAPA performance, but a higher dose of SCH23390 caused a motor
      deficit in the retrieval session. We conclude that in the previous study, D1
      active drugs may have had influence upon the non-spatial aspects of the AAPA.

PMID- 17207867
TI  - Preventive effect of kami-untan-to on performance in the forced swimming test in
      thiamine-deficient mice: relationship to functions of catecholaminergic neurons.
AB  - The kampo (Japanese herbal) medicine "kami-untan-to" (KUT) has been used for a
      long time in the treatment of neuropsychiatric disorders. We have recently
      reported that mice put on a thiamine-deficient (TD) diet exhibit a depressive
      behavior and impairment in avoidance learning after 20 days, and that this
      impairment was reversed by the chronic administration of KUT. In the present
      study, we investigated the effect of KUT on the depressive behavior observed in
      TD mice by using the forced swimming test. Our results show that oral
      administration of KUT from the 1st day of TD feeding prevented the increased
      duration of immobility in TD mice. Administration of KUT from the 10th day of TD
      feeding also had a beneficial effect on depressive behavior. To examine the
      relationship between the potential effects of KUT on monoaminergic neuronal
      functions and the depressive behavior observed in TD mice, we measured the
      immunohistochemical distribution of tyrosine hydroxylase (TH) in the brain using
      microphotometry. The fluorescence intensity of TH decreased in the limbic cortex
      and brainstem in TD mice compared with pair-fed mice as the control group, while
      KUT treatment protected against these decreases. These results suggest that KUT
      treatment may prevent a sign of depressive behavior, the animal immobility time,
      induced by TD feeding through a mechanism that involves the decrease of TH in
      some brain areas of TD mice.

PMID- 17207866
TI  - Strychnine and taurine modulation of amygdala-associated anxiety-like behavior is
      'state' dependent.
AB  - Strychnine-sensitive glycine receptors are expressed in many adult forebrain
      regions, yet the biological function of these receptors outside the spinal
      cord/brainstem is poorly understood. We have recently shown that rat
      lateral/basolateral amygdala neurons express strychnine-sensitive glycine-gated
      currents whose pharmacological and molecular characteristics are consistent with
      those established for classic ligand-gated chloride channels. The current studies
      were undertaken to establish the behavioral role, if any, of these strychnine
      sensitive glycine receptors. Adult Long-Evans male rats were implanted with guide
      cannulae targeted at the lateral amygdala and were microinjected with standard
      artificial cerebrospinal fluid with or without various doses of strychnine or
      taurine. Anxiety-like behaviors were assessed with the elevated plus maze or the
      light/dark box. In the elevated plus maze, strychnine decreased closed-arm time
      and increased open-arm time, suggestive of an anxiolytic effect. Similarly,
      strychnine produced a modest anxiolytic effect in the light/dark box. Post hoc
      analysis of 'open-arm' time and 'light-side' time indicated that aCSF-treated
      animals were distributed into two apparent groups that displayed either high or
      low amounts of anxiety-like behavior in a given apparatus. Surprisingly, the
      pharmacological effects of both strychnine and taurine in these assays were
      dependent upon a given animal's behavioral phenotype. Together, these findings
      are significant because they suggest that the basal 'emotional state' of the
      animal could influence the behavioral outcome associated with drug application
      directly into the lateral/basolateral amygdala. Furthermore, our findings also
      suggest that compounds acting at amygdala strychnine-sensitive glycine receptors
      may actively modulate this basal anxiety-like state.

PMID- 17207868
TI  - Effects of alkylphenols on the reproductive system of Atlantic cod (Gadus
      morhua).
AB  - Produced water, a by-product of offshore oil production, contains significant
      amounts of alkylphenols (APs). Many studies have shown that APs cause endocrine
      disruption in marine organisms, but relatively little is currently known about
      their long-term effects on the biology of pelagic fish. Here, we describe in
      detail the effects of APs on the reproductive potential of first-time spawning
      Atlantic cod (Gadus morhua). Cod were fed with feed paste containing four APs (4
      tert-butylphenol, 4-n-pentylphenol, 4-n-hexylphenol and 4-n-heptylphenol), at a
      range of concentrations, for either 1 or 5 weeks. AP-exposed fish were compared
      to unexposed fish and to fish fed paste containing natural estrogen (17beta
      estradiol). Our results showed that in female fish AP exposure impaired oocyte
      development, reduced estrogen levels, and delayed the estimated time of spawning
      by 17-28 days. Similarly, in male fish, we observed that AP-exposure reduced 11
      keto-testosterone concentrations, and caused a small induction of VTG levels. We
      also observed impaired testicular development, with an increase in the amount of
      spermatogonia and a reduction in the amount of spermatozoa present. Taken
      together these results suggest that APs released into the sea via produced water
      may have a negative influence on the overall reproductive fitness of cod
      populations.

PMID- 17207869
TI  - Relationship between renal and cardiovascular changes in a murine model of
      glucose intolerance.
AB  - Nutrition is an important variable which may affect the risk for renal disease.
      We previously showed that a high fructose diet in mice produced hypertension and
      sympathetic activation [8]. The purpose of this study was to determine if a
      fructose diet altered renal function. A high fructose diet for 12 weeks impaired
      glucose tolerance, but caused no change in body weight, blood glucose or plasma
      insulin. Impairment in renal function was documented by the almost two fold
      increase in urinary protein excretion ( CONTROL: 6.6+/-0.6 vs. Fructose: 15.0+/
      0.7 mmol protein/mmol creatinine; p<0.05) which was also accompanied by increases
      in urinary volume. The diet produced little change in renal histology, kidney
      weight or kidney weight/body weight ratio. Urinary excretion of angiotensin
      II/creatinine ( CONTROL: 78.9+/-16.6 vs. Fructose: 80.5+/-14.2 pg/mmol) and renal
      angiotensin converting enzyme activity ( CONTROL: 9.2+/-1.6 vs. Fructose: 7.6+/
      1.0 ACE units) were not different between groups. There was a positive
      correlation between mean arterial pressure (r=0.7, p=0.01), blood pressure
      variability (BPV) (r=0.7, p=0.02), low frequency BPV component (r=0.677, p=0.03)
      and urinary protein excretion. Results show that consumption of a high fructose
      diet in mice had deleterious effects on renal function, which were correlated
      with cardiovascular changes.

PMID- 17207870
TI  - Transcriptional regulation of the Drosophila caudal homeobox gene by bHLH-PAS
      proteins.
AB  - Caudal-related homeobox transcription factors are involved in the definition of
      the anteroposterior axis and intestinal development. Recent reports indicate that
      dysregulation of CDX1 and CDX2, the human homologues of Drosophila caudal, are
      associated with several types of cancer. Very little is known, however, about the
      regulatory mechanisms that direct the caudal-related homeobox gene expression. In
      this study, we have identified the binding sites for bHLH-PAS proteins, referred
      to as CNS midline element (CME), in the 5'-flanking region of the Drosophila
      caudal gene. Analyses using transgenic flies carrying a caudal-lacZ fusion gene
      bearing a wild-type or mutant CME indicate that the CME sites are required for
      caudal gene expression in vivo. We also determined that the caudal promoter
      activity can be regulated by Trachealess (Trh)/Tango (Tgo) bHLH-PAS proteins, via
      the CME sites. Our results suggest that the Drosophila caudal gene is a target of
      the Trh/Tgo bHLH-PAS proteins.

PMID- 17207871
TI  - Pf-ALMP, a novel astacin-like metalloproteinase with cysteine arrays, is abundant
      in hemocytes of pearl oyster Pinctada fucata.
AB  - The astacin family metalloproteinase is a family of zinc-dependent endopeptidases
      which play crucial roles in embryonic development, bone growth and morphogenesis.
      A cDNA clone encoding a putative astacin-like metalloproteinase (pf-ALMP) was
      isolated from hemocytes of pearl oyster, Pinctada fucata. The novel
      metalloproteinase presents a molecular organization close to the astacins, but
      has a novel C-terminal domain with cysteine arrays. RT-PCR analysis revealed that
      pf-ALMP was expressed dramatically high in hemocytes, which was affected by
      lipopolysaccharides (LPS) challenge. High expression of pf-ALMP was also found in
      gill, gonad and digestion gland, and in situ hybridization demonstrated that pf
      ALMP was expressed in the epithelia cells of these tissues. Substrate analysis
      studies indicated that the recombinant pf-ALMP catalytic domain could digest
      gelatin. Interestingly, the pf-ALMP also could be involved in cell proliferation
      processes and the cysteine arrays were necessary for the proliferative activity.
      Taken together, these studies also help to further understand the functions of
      astacins which may be related to the processes of molluscan inflammatory
      response, embryo development, proliferation and shell formation.

PMID- 17207872
TI  - Health and motivation of elderly relocating to a suburban area in Japan.
AB  - In Japan, few studies have investigated the effects of moving residence among the
      elderly, despite the fact that Japanese elderly will be increasingly required to
      switch residence in the future. Here, we used representative sampling to examine
      the characteristics of elderly persons who had moved residence to a Tokyo suburb
      and compared results with those of non-moving residents of the suburb. Movers
      aged 65 years old or older who had relocated within the previous 2 years (movers)
      and residents aged 65 years old or older and had lived in the area longer than 5
      years (non-movers) were surveyed by mail in 2004, with a focus on health and
      psychosocial measures. Compared with non-movers (N=117), movers (N=97) were more
      depressed, socially isolated, and fulfilled less active social roles among family
      members. The majority of movers had moved to find affordable housing or to live
      with or near family. Two factors preceded co-residence with family, namely
      retirement and imminent loss of functional independence. Our findings suggest
      that movers require community support to prevent social isolation, dependency and
      health declines.

PMID- 17207873
TI  - Elevated IgG titers to periodontal pathogens related to Buerger disease.
AB  - BACKGROUND: Periodontal pathogens were frequently detected in the occluded
      arteries of Buerger disease patients, hence we hypothesized that the infection
      from periodontal pathogens may be associated with Buerger disease. METHODS: We
      investigated periodontal status using various clinical parameters and serum IgG
      antibody levels against T. denticola, P. gingivalis, A. actinomycetemcomitans and
      P. intermedia in nineteen Buerger disease patients and fifteen control subjects.
      The results were statistically analyzed. RESULTS: The prevalence of periodontitis
      and the percentages of probing sites with PD> or =4 mm and CAL> or =4 mm were
      significantly higher in the patient group (P<0.001, P=0.016, and P<0.001,
      respectively). Patients had significantly higher serum IgG titers against T.
      denticola, P. gingivalis and A. actinomycetemcomitans (P=0.002, P=0.039, and
      P=0.011, respectively). CONCLUSIONS: This study provides evidence for possible
      implications of periodontitis in Buerger disease.

PMID- 17207874
TI  - Transcriptome analysis reveals the population of dendritic RNAs and their
      redistribution by neural activity.
AB  - Subcellular localization of RNA is an efficient way to localize proteins to a
      specific region of a cell. The dendritic localization of RNAs underlies the
      establishment and maintenance of the synaptic functions of neuronal cells. A
      requirement for dendritic RNA localization and subsequent local translation has
      been demonstrated in several forms of experience-dependent synaptic plasticity.
      In spite of several attempts to identify these RNAs, the population of RNA
      species present in dendrites as a whole has not been well described. Here we show
      the results of microarray analyses with RNAs isolated from heavy portion of
      polysome (HP) fraction where RNA granules are enriched in and synaptosome
      fraction, prepared from the rat brain. These analyses revealed the complex nature
      of the dendritic RNA population, which included RNAs that were not expected to be
      in the dendrites. Neural activity caused by an electroconvulsive shock triggered
      a redistribution of the population of dendritic transcriptome towards the area of
      overlap between the HP and the synaptosome, which is assumed to be neck of spine.
      This redistribution may accompany some changes in the translatability of those
      transcriptome, which suggests complex mechanisms of local translation in response
      to synaptic inputs.

PMID- 17207875
TI  - Attachment of Shiga toxigenic Escherichia coli to stainless steel.
AB  - Shiga toxigenic Escherichia coli (STEC) are important foodborne pathogens causing
      gastrointestinal disease worldwide. Bacterial attachment to food surfaces, such
      as stainless steel may lead to cross contamination of foods and subsequent
      foodborne disease. A variety of STEC isolates, including E. coli O157:H7/H-
      strains, were grown in planktonic (broth) and sessile (agar) culture, following
      which initial attachment to stainless steel was determined using epifluorescence
      microscopy. Experiments were performed to determine whether the number of
      bacteria attached to stainless steel differed between STEC strains and between
      the two modes of growth. No relationship was found between STEC strains and the
      number of bacteria attached to stainless steel. Five STEC strains, including one
      non-toxigenic O157 isolate, attached in significantly greater (p<0.05) numbers to
      stainless steel following growth in planktonic culture compared to sessile
      culture. In contrast, two clinical strains of O157:H7 attached in significantly
      greater (p<0.05) numbers following growth in sessile culture compared to
      planktonic culture. Thirteen out of twenty E. coli strains showed no significant
      difference (p>0.05) in attachment when grown in planktonic or sessile culture.
      The change of interfacial free energy between the bacterial strains and stainless
      steel was calculated and the influence of free energy in attachment was
      determined. Although a significant variation (p<0.05) in free energy values was
      found between STEC strains, no correlation was found between free energy values
      and bacterial counts on stainless steel. In addition, no correlation was also
      found between bacterial hydrophobicity and surface charge values or production of
      surface structures (type I fimbriae or flagella) (previously determined) with the
      number of bacteria attached to stainless steel. The results of this study suggest
      that different growth conditions (planktonic and sessile) can influence the
      attachment of STEC to stainless steel. Factors other than bacterial
      physicochemical properties and these surface structures may also influence STEC
      attachment to stainless steel.

PMID- 17207876
TI  - Molecular tools for metalloprotease sub-proteome generation.
AB  - Molecular systems biology, the highly challenging post-genomic research area has
      many different facets like transcriptomics, proteomics, metabolomics,
      interactomics, modelling of cell cycles, etc. Among them, functional proteomics
      and interactomics represent exciting fields of research with high relevance
      towards biochemistry, medicinal chemistry, therapy, biotechnology and
      bioinformatics. The number of different proteins expressed by a cell under a set
      of certain conditions and the high dynamic range of these proteins together with
      different activation states require methods for sub-proteome generation on a
      mechanistic basis to reduce the amount of data. This can be achieved by
      application of tailor-made molecular tools that are based on inhibitors or, more
      generally, on protein ligands. Immobilised protein ligands proved to be suitable
      for the generation of sub-proteomes by affinity chromatography or by fishing
      using magnetic beads. Metalloproteases share a catalytically active metal ion in
      the active site. They can for example be addressed by hydroxamate type inhibitors
      like marimastat which are suitable for targeting active metalloproteases on a
      mechanistic basis aiming at the generation of an activity- and affinity-based sub
      proteome. For such purposes, modified hydroxamate type inhibitors can be attached
      to a solid surface, e.g., chromatography material, magnetic beads, or a surface
      plasmon resonance sensor chip. The latter technique is a valuable tool for the
      optimisation of binding and elution conditions of biomolecules in affinity
      chromatography or on experiments using magnetic beads. Preliminary results are
      reported on the application of these probes in fishing experiments using magnetic
      beads.

PMID- 17207877
TI  - Metabolic flux analysis at ultra short time scale: isotopically non-stationary
      13C labeling experiments.
AB  - A novel approach to (13)C metabolic flux analysis (MFA) is presented using
      cytosolic metabolite pool sizes and their (13)C labeling data from an
      isotopically non-stationary (13)C labeling experiment (INST-CLE). The procedure
      is demonstrated with an E. coli wild type strain grown at fed batch conditions.
      The intra cellular labeling dynamics are excited by a sudden step increase of the
      (13)C portion in the substrate feed. Due to unchanged saturation of the substrate
      uptake system, the metabolic fluxes remain constant during the following sampling
      time period of only 16s, in which 20 samples are taken by an automated rapid
      sampling device immediately stopping metabolism by methanol quenching. Subsequent
      cell disruptive sample preparation and LC-MS/MS enabled simultaneous
      determination of pool sizes and mass isotopomers of intra cellular metabolites
      requiring detection limits in the nM range. Based on this data the new
      computational flux analysis tool 13CFLUX/INST is used to determine the intra
      cellular fluxes based on a complex carbon labeling network model. The measured
      data is in good agreement with the model predictions, thus proving the
      applicability of the new isotopically non-stationary (13)C metabolic flux
      analysis (INST-(13)C-MFA) concept. Moreover, it is shown that significant new
      information with respect to flux identifiability, non-measurable pool sizes, data
      consistency, or large storage pools can be taken from the novel kind of
      experimental data. This offers new insight into the biological operation of the
      metabolic network in vivo.

PMID- 17207878
TI  - Redox regulation and antioxidative defence in Arabidopsis leaves viewed from a
      systems biology perspective.
AB  - Redox regulation is a central control element in cell metabolism. It is employed
      to adjust photosynthesis and the antioxidant defence system of leaves to the
      prevailing environment. During recent years progress has been made in describing
      the redox-dependent alterations in metabolism, the thiol/disulfide proteome, the
      redox-dependent and cross-talking signalling pathways and the target genes of
      redox regulation. Some transcription factors have been identified as proteins
      that perform thiol/disulfide transitions linked to the redox-regulation of
      specific plant promoters. In addition first mathematical models have been
      designed to simulate antioxidant defence and predict its response. Taken
      together, a profound experimental data set has been generated which allows to
      approach a systems biology type of understanding of antioxidant defence in
      photosynthesising cells in the near future. Since oxidative stress is likely to
      limit plant growth under stress, such a systematic understanding of antioxidant
      defence will help to define novel targets for breeding stress-tolerant plants.

PMID- 17207879
TI  - Poly(ethylene carbonate): a thermoelastic and biodegradable biomaterial for drug
      eluting stent coatings?
AB  - A first feasibility study exploring the utility of poly(ethylene carbonate) (PEC)
      as coating material for drug eluting stents under in vitro conditions is
      reported. PEC (Mw 242 kDa, Mw/Mn=1.90) was found to be an amorphous polymer with
      thermoelastic properties. Tensile testing revealed a stress to strain failure of
      more than 600%. These properties are thought to be advantageous for expanding
      coated stents. In vitro cytotoxicity tests showed excellent cytocompatibility of
      PEC. Based on these findings, a new stenting concept was suggested, pre-coating a
      bare-metal stent with PPX-N as non-biodegradable basis and applying a secondary
      PEC coating using an airbrush method. After manual expansion, no delamination or
      destruction of the coating could be observed using scanning electron microscopy.
      The surface degradation-controlled release mechanism of PEC may provide the basis
      for "on demand" drug eluting stent coatings, releasing an incorporated drug
      predominantly at an inflamed implantation site upon direct contact with
      superoxide-releasing macrophages. As a release model, metal plates of a defined
      size and area were coated under the same conditions as the stents with PEC
      containing radiolabelled paclitaxel. An alkaline KO(2-) solution served as a
      superoxide source. Within 12 h, 100% of the incorporated paclitaxel was released,
      while only 20% of the drug was released in non-superoxide releasing control
      buffer within 3 weeks.

PMID- 17207880
TI  - High-yield production of biologically active mono-PEGylated salmon calcitonin by
      site-specific PEGylation.
AB  - The purpose of this study was to develop and optimize a unique one-pot, two-step
      site-specific PEGylation method suitable for the high-yield production of mono
      PEGylated (Lys(18)) salmon calcitonin (Lys(18)-PEG-sCT), which was previously
      demonstrated to have superior pharmaceutical properties to other conjugates. For
      the site-specific PEGylation, this study used the sCT derivative (FMOC(1,11)
      sCT), which was FMOC protected at Cys(1)- and Lys(11)-amines among three
      PEGylation sites including Lys(18)-amine. This PEGylation process was achieved by
      the consecutive one-pot, two-step reaction: (i) the PEG conjugation to FMOC(1,11)
      sCT; and (ii) the subsequent deprotection of FMOC group from the PEGylated
      FMOC(1,11)-sCT. The optimized reaction resulted in the high production yield of
      Lys(18)-PEG-sCT (about 86%), compared with that from conventional non-specific
      PEGylation (about 18%). The prepared Lys(18)-PEG-sCT conjugate showed improved
      biological stability without the loss in the in vitro and in vivo biological
      activity by PEGylation. Consequently, this site-specific PEGylation using an FMOC
      protection/deprotection strategy showed great usefulness in the production of the
      most promising Lys(18)-PEG-sCT conjugate with a high yield.

PMID- 17207881
TI  - Bone regeneration through controlled release of bone morphogenetic protein-2 from
      3-D tissue engineered nano-scaffold.
AB  - The objective of the present study was to enhance ectopic bone formation through
      the controlled release of bone morphogenetic protein-2 (BMP-2) from an injectable
      three dimensional (3-D) tissue engineered nano-scaffold. We demonstrate that a 3
      D scaffold can be formed by mixing of peptide-amphiphile (PA) aqueous solution
      with BMP-2 suspension. A 3-D network of nanofibers was formed by mixing BMP-2
      suspensions with dilute aqueous solutions of PA. Scanning electron microscopy
      (SEM) observation revealed the formation of fibrous assemblies with an extremely
      high aspect ratio and high surface areas. In vivo release profile of BMP-2 from 3
      D network of nanofibers was investigated. In addition, ectopic bone formation
      induced by the released BMP-2 was assessed in a rat model using histological and
      biochemical examinations. It was demonstrated that the injection of an aqueous
      solution of PA together with BMP-2 into the back subcutis of rats, resulted in
      the formation of a transparent 3-D hydrogel at the injected site and induced
      significant homogeneous ectopic bone formation around the injected site, in
      marked contrast to BMP-2 injection alone or PA injection alone. The combination
      of BMP-2-induced bone formation is a promising procedure to improve tissue
      regeneration.

PMID- 17207882
TI  - Effect of excipients on PLGA film degradation and the stability of an
      incorporated peptide.
AB  - The effect of pH modifying excipients on the chemical stability of a model
      peptide (VYPNGA) and the degradation of poly(dl-lactide-co-glycolide)(PLGA) was
      studied in PLGA films under accelerated storage conditions. pH modifiers included
      a basic amine (proton sponge), a basic salt (magnesium hydroxide) and two pH
      buffers (ammonium acetate and magnesium acetate). Changes in film pH were
      monitored using (13)C NMR, peptide degradation products were quantified by
      LC/MS/MS and PLGA degradation was analyzed by TGA, DSC and SEC. Inclusion of pH
      modifiers had little impact on PLGA degradation. The proton sponge affected an
      initial decrease in pH but reduced peptide deamidation and chain cleavage
      relative to an unbuffered control. Magnesium hydroxide produced an initial
      increase in pH but also showed increased peptide deamidation. Ammonium acetate
      decreased pH and increased peptide chain cleavage, presumably due to increased
      PLGA hydrolysis. Magnesium acetate buffer increased the initial pH but resulted
      in increased peptide loss. The extent of peptide acylation increased in all
      formulations, most notably in the proton sponge modified films. The effectiveness
      of pH modifiers in PLGA formulations under storage conditions is dependant on
      both the mechanism of pH alteration and the peptide degradation reaction of
      interest.

PMID- 17207883
TI  - A cleavable molecular adapter reduces side effects and concomitantly enhances
      efficacy in tumor treatment by targeted toxins in mice.
AB  - Two of the main problems associated with administration of receptor-targeted
      toxins in tumor therapy are severe systemic side effects and low transfer of the
      toxins into the cytosol after binding to the tumor cell surface. To improve
      chimeric toxins in this respect we have developed a molecular adapter that links
      the toxic moiety and ligand. The adapter is designed to improve cytosolic uptake,
      retain the toxin inside the cytosol and detoxify the drug after cell death. The
      plant toxin saporin linked either directly or via the adapter to epidermal growth
      factor (EGF) served to evaluate efficacy to inhibit tumor growth and reduce side
      effects in vivo. The lethal dose for BALB/c mice was three times less for the
      adapter-containing toxin (SA2E) than for the adapter-free construct (SE).
      Furthermore, SE only reduced the average weight of induced tumors by 33% whereas
      SA2E-treated mice exhibited 71% reduction with an almost complete suppression in
      60% of the cases. Additionally, severe side effects like hyperalgesia, alopecia
      and death were drastically reduced in SA2E-treated animals. Tumors without target
      receptor were only slightly affected by SA2E and the reduction in side effects
      less pronounced indicating specific depletion from the blood by target receptor
      expressing cells.

PMID- 17207884
TI  - Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic
      F127 hydrogel for subcutaneous administration: In vitro and in vivo
      characterization.
AB  - Here we investigated thermo-sensitive Pluronic(R) F127 (PF127) hydrogel for the
      controlled release of peptide and protein drugs after subcutaneous injection,
      using an antithrombotic polypeptide, recombinant hirudin variant-2 (rHV2), as the
      model drug. The in vitro release experiment performed with a membrane-less model
      at 37 degrees C showed that the release of antithrombotic activity of rHV2 from
      PF127 gel followed zero-order kinetics and correlated well with the weight
      percentage of PF127 dissolved, indicating a dissolution-controlled release
      mechanism. The in vivo result obtained after subcutaneous injection of rHV2
      loaded PF127 gel in normal rats demonstrated that PF127 gel improved the
      bioavailability, prolonged the antithrombotic effect of rHV2, and induced
      detectable plasma rHV2 concentration for a longer time in comparison with rHV2
      aqueous solution. Differential scanning calorimetry, dynamic light scattering and
      Fourier transform infrared spectroscopy provided evidence of the interaction
      between PF127 and rHV2, but such interaction was unlikely to interfere the
      feasibility of this drug delivery system. Our current in vitro and in vivo study
      suggested that PF127 gel may be useful as an injectable delivery vehicle for
      peptides and proteins with short half-lives to prolong their therapeutic effect,
      increase their bioavailability and improve the clinic outcome.

PMID- 17207885
TI  - Impact of the sulfonylurea receptor 1 (SUR1) exon 16-3c/t polymorphism on acute
      hyperglycaemia in type 2 diabetic patients.
AB  - Epidemiological data collected over the last few decades have demonstrated the
      significant role of acute (especially postprandial) hyperglycaemia in the
      development of macrovascular complications in patients with type 2 diabetes.
      However, the influence of SUR1 exon 16-3c/t polymorphism on impaired insulin
      secretion during acute hyperglycaemic episodes has not yet been evaluated. We
      studied 40 type 2 diabetic patients. Single nucleotide polymorphism in the
      sulfonylurea receptor gene was examined by means of PCR-RLFP. In every patient,
      fasting insulin, proinsulin, C-peptide and 1,5-anhydro-d-glucitol concentrations
      were assayed as markers of insulin secretion, peripheral resistance to insulin,
      and acute hyperglycaemia. The distribution of SUR1 exon 16-3c/t polymorphism was
      tt 35%, tc -40%, and cc -25%. By means of analysis of covariance, it was revealed
      that 1,5-anhydro-d-glucitol plasma levels are associated with SUR1 exon 16-3c/t
      polymorphism. However, the HOMA(IR) score influenced 1,5-anhydro-d-glucitol
      levels in plasma at a higher level of statistical power than the genetic variant.
      Our results suggest that SUR1 exon 16-3c/t polymorphism is only a partial
      determinant of acute hyperglycaemia-cardiovascular risk factor in type 2
      diabetes.

PMID- 17207886
TI  - Conditional reimbursement within the Dutch drug policy.
AB  - In The Netherlands, conditional reimbursement is considered to be a promising
      approach to achieving more effective and efficient pharmaceutical care. Because
      of its formal status and nationwide regulation, conditional reimbursement may
      allow governments to better control medical decision-making. To evaluate the
      effects of conditional reimbursement on medicine use and its performance as a
      policy tool, we compared observed volumes of medicine use with expected volumes.
      In addition, we mapped the annual growth by analysing trends in the volumes of
      use of all conditionally reimbursed drugs; starting with the year the drug
      entered the market (using macro-level data). Next we explored five cases in depth
      (using micro-level data) in order to explore what fraction of individual
      prescriptions met the requirements. We also performed qualitative research
      (document analysis, interviews (N=65)) in order to obtain the stakeholders'
      perspectives on how the measure functions, as well as to interpret the case
      studies data further. The findings suggest that conditional reimbursement may be
      an effective policy instrument, but that several changes are needed to optimize
      its impact. These changes are predominantly related to transparency (e.g.
      conditions are set following clear procedures and criteria), legitimacy
      (conditions should be consistent with criteria for prioritization), feasibility
      of procedures to control appropriate use, and timely and appropriate commitment
      of the stakeholders.

PMID- 17207888
TI  - Semiautomated finite element mesh generation methods for a long bone.
AB  - The objective of this work was to develop and test a semi-automated finite
      element mesh generation method using computed tomography (CT) image data of a
      canine radius. The present study employs a direct conversion from CT Hounsfield
      units to elastic moduli. Our method attempts to minimize user interaction and
      eliminate the need for mesh smoothing to produce a model suitable for finite
      element analysis. Validation of the computational model was conducted by loading
      the CT-imaged canine radius in four-point bending and using strain gages to
      record resultant strains that were then compared to strains calculated with the
      computational model. Geometry-based and uniform modulus voxel-based models were
      also constructed from the same imaging data set and compared. The nonuniform
      voxel-based model most accurately predicted the axial strain response of the
      sample bone (R(2)=0.9764).

PMID- 17207887
TI  - What can microbial genetics teach sociobiology?
AB  - Progress in our understanding of sociobiology has occurred with little knowledge
      of the genetic mechanisms that underlie social traits. However, several recent
      studies have described microbial genes that affect social traits, thereby
      bringing genetics to sociobiology. A key finding is that simple genetic changes
      can have marked social consequences, and mutations that affect cheating and
      recognition behaviors have been discovered. The study of these mutants confirms a
      central theoretical prediction of social evolution: that genetic relatedness
      promotes cooperation. Microbial genetics also provides an important new
      perspective: that the genome-to-phenome mapping of social organisms might be
      organized to constrain the evolution of social cheaters. This constraint can
      occur both through pleiotropic genes that link cheating to a personal cost and
      through the existence of phoenix genes, which rescue cooperative systems from
      selfish and destructive strategies. These new insights show the power of studying
      microorganisms to improve our understanding of the evolution of cooperation.

PMID- 17207889
TI  - Urokinase plasminogen activator and plasminogen activator inhibitor type-1 in
      nonsmall-cell lung cancer: relation to prognosis and angiogenesis.
AB  - BACKGROUND: Urokinase plasminogen activator (uPA) and plasminogen activator
      inhibitor type-1 (PAI-1) have previously been suggested as prognostic markers in
      nonsmall-cell lung carcinomas (NSCLC). We investigate whether uPA and PAI-1 are
      prognostic markers in NSCLC and whether they are related to angiogenesis.
      MATERIALS AND METHODS: Frozen tumour tissue from surgical specimens from 118
      previously untreated patients diagnosed with NSCLC in the period 1984-1991 were
      investigated. All patients were treated with surgery, and no chemo- or
      radiotherapy was given. UPA and PAI-1 levels were assessed using a sandwich ELISA
      method. RESULTS: Both uPA and PAI-1 were independent of classical
      histopathological parameters as well as of microvessel density and vascular
      pattern. Using death within the first 5 years as endpoint, neither of the factors
      were prognostic markers in univariate analysis, however, significantly higher
      levels of uPA and PAI-1 were seen in tumours with an angiogenic vascular pattern.
      In multivariate analysis, high disease stage (P<0.0001), adenocarcinoma
      (P=0.007), old age (P=0.02), and presence of an angiogenic pattern (P=0.05) were
      identified as independent markers of death within 5 years. CONCLUSIONS: The
      present study investigated the prognostic role of the protein levels of uPA and
      PAI-1 in 118 tumour specimens from patients diagnosed with NSCLC. Neither of the
      factors were identified as prognostic markers when evaluated with survival as
      endpoint. However, in tumours previously identified as non-angiogenic we found
      significantly lower contents of both uPA and PAI-1 as compared to angiogenic
      tumours, thus we hypothesize that uPA and PAI-1 stimulate angiogenesis in NSCLC.

PMID- 17207890
TI  - Differential regulation of RANTES and IL-8 expression in lung adenocarcinoma
      cells.
AB  - In lung adenocarcinoma, expression of Regulated upon Activation, Normal T cell
      Expressed and presumably Secreted (RANTES) is a predictor of survival while that
      of interleukin (IL)-8 is associated with a poor prognosis. In several models,
      tumorigenesis is abolished by RANTES, while it is facilitated by IL-8. We studied
      the regulation of RANTES and IL-8 expression in A549 lung adenocarcinoma cells.
      The effects of tumor necrosis factor (TNF)-alpha and regulators of protein
      kinases C (PKC)alpha/beta were tested because these have been shown to modulate
      cancer development and progression. TNF-alpha stimulated expression of both
      chemokines, while the PKCalpha/beta activator 12-O-tetradecanoyl-phorbol-13
      acetate (TPA) induced only expression of IL-8 and inhibited TNF-alpha-induced
      RANTES expression. The PKCalpha/beta inhibitor Go 6976 increased TNF-alpha
      induced RANTES production and prevented its down-regulation by TPA. In contrast,
      it decreased TNF-alpha or TPA-induced IL-8 release. The differential regulation
      of RANTES and IL-8 expression was further analyzed. Site-directed mutagenesis
      indicated that regulation of RANTES promoter activity required two nuclear factor
      (NF)-kappaB response elements but not its activator protein (AP)-1 binding sites.
      An AP-1 and a NF-kappaB recognition sites were necessary for full induction of IL
      8 promoter activity by TNF-alpha and TPA. Moreover, electrophoretic mobility
      shift assays demonstrated that NF-kappaB response elements from the RANTES
      promoter were of lower affinity than that from the IL-8 promoter. Immunoblotting
      experiments showed that TPA was more potent than TNF-alpha to induce in a
      PKCalpha/beta dependent manner the p44/p42 mitogen-activated protein kinases
      (MAPK) signaling cascade which controls AP-1 activity. Conversely, TPA inhibited
      TNF-alpha-induced NF-kappaB signaling and was a weak activator of this pathway.
      Thus, TPA did not sufficiently activate NF-kappaB to increase transcription
      through the low affinity NF-kappaB binding sites on RANTES promoter and its
      inhibitory effect on TNF-alpha-induced NF-kappaB signaling resulted in a reduced
      transcription rate. On IL-8 promoter, increased transcription through the high
      affinity NF-kappaB binding site occurred even with poorly activated NF-kappaB and
      the functional AP-1 response element compensated any loss of transcription rate.
      These data provide a mechanistic insight into the differential regulation of IL-8
      and RANTES expression by PKCalpha/beta in lung adenocarcinoma cells.

PMID- 17207891
TI  - Seasonal and geographical variations in lung cancer prognosis in Norway. Does
      Vitamin D from the sun play a role?
AB  - Vitamin D derivatives can modulate proliferation and differentiation of cancer
      cells. Our main source of Vitamin D is ultraviolet (UV) radiation-induced
      synthesis in skin following sun exposure. UV measurements show that the ambient
      annual UV exposures increase by about 50% from north to south in Norway. As
      judged from the incidence rates of squamous cell carcinoma, the same is true for
      the average personal UV exposures. Solar ultraviolet B (UVB) (280-320nm) exhibits
      a strong seasonal variation with a minimum during the winter months. The present
      work aims at investigating the impact of season of diagnosis and residential
      region, both influencing the Vitamin D level, on the risk of death from lung
      cancer in patients diagnosed in Norway. Data on all incident cases of lung cancer
      between 1964 and 2000 were collected. Risk estimates were calculated as relative
      risk (RR), with 95% confidence intervals using Cox regression model. The seasonal
      variation of 25-hydroxyvitamin D was assessed from routine measurements of 15,616
      samples performed at The Hormone Laboratory of Aker University Hospital. Our
      results indicate that season of diagnosis is of prognostic value for lung cancer
      patients, with a approximately 15% lower case fatality for young male patients
      diagnosed during autumn versus winter (RR=0.85; 95% CI, -0.73 to 0.99; p=0.04).
      Residing in a high UV region resulted in a further lowering of the death risk
      than residing in a low UV region. We propose, in agreement with earlier findings
      for prostate-, breast- colon cancer and Hodgkins lymphoma, that a high level of
      sun-induced 25-hydroxyvitamin D can be a prognostic advantage for certain groups
      of lung cancer patients, notably for young men. Lung cancer has for several
      decades been the leading cause of cancer-related mortality in men in Norway and
      during the last two decades, became the second most common cause of cancer
      related death in women . There are two main types of lung cancer: small cell lung
      cancer for which chemotherapy is the primary treatment and non-small cell lung
      cancer, which in its early stages is treated primarily with surgery. Gender
      related differences have been described in the literature with respect to
      survival after therapy, male gender being a significant independent negative
      prognostic factor . In Norway the 5 years relative survival for localized tumours
      is about 30% for females and 20% for males. Calcitriol, which is the most active
      form of Vitamin D, is involved in key regulatory processes such as proliferation,
      differentiation and apoptosis in a wide variety of cells . Mechanisms for these
      actions have been proposed to be the interaction of active Vitamin D derivatives
      with a specific nuclear receptor (VDR receptor) and/or with membrane targets . In
      vitro studies, performed with lung cancer cell lines, have shown an inhibitive
      effect of Vitamin D derivatives on cell-growth and proliferation . Furthermore,
      animal studies have demonstrated the capability of these compounds to suppress
      invasion, metastasis and angiogenesis in vivo , suggesting that administration of
      Vitamin D derivatives may be used as adjuvant therapy for lung cancer. Humans get
      optimal Vitamin D levels by exposure to sun or artificial ultraviolet B (UVB, 280
      320nm) sources , and possibly also by consumption of food rich in this nutrient
      (fat fish, eggs, margarine, etc.) or of vitamin supplements . Among these
      sources, solar radiation appears to be the most important one . Thus, the Vitamin
      D status (assessed by the serum levels of 25-hydroxyvitamin D, calcidiol)
      exhibits a strong seasonal variation that parallels the seasonal change in the
      fluence of solar UVB that reaches the ground. During winter, the UVB fluence rate
      in the Nordic countries (50-71 degrees N) is below the level required for Vitamin
      D synthesis in skin . The maximal level of calcidiol is reached between the
      months July and September, and is 20-120% higher than the corresponding winter
      level . Recently we hypothesised that the seasonal variation of calcidiol might
      be of prognostic significance for colon-, breast- prostate cancer as well as for
      Hodgkins lymphoma in Norway. Patients diagnosed during summer and autumn have a
      better survival after standard treatment than patients diagnosed during the
      winter season . This might be a consequence of a higher Vitamin D level. An
      American study investigated the effect of season of surgery and recent Vitamin D
      intake on the survival of non-small cell lung cancer patients. The authors
      reported a significant beneficial joint effect of summer season and high Vitamin
      D intake compared with winter season and low Vitamin D intake while Vitamin D
      intake alone did not affect prognosis. Similar results were recently reported
      from a large study in United Kingdom involving over a million cancer patients
      including over 190,000 patients diagnosed with lung cancer . Norway (58-71
      degrees N) has a significant north-south variation in UV fluence. This makes the
      country suitable for studies relating cancer epidemiology to UV levels . We
      investigated whether variations in UV, and, consequently, in Vitamin D level,
      influence the prognosis of lung cancer, using season of diagnosis and residential
      regions as variables. Survival data obtained for patients diagnosed over a 40
      years period were compared with variations in serum Vitamin D levels obtained
      from routine measurements performed in The Hormone Laboratory of Aker University
      Hospital during the period 1996-2001. Seasonal and gender variations in Vitamin D
      level have been estimated from the analyses.

PMID- 17207892
TI  - Hot water flushing for immiscible displacement of a viscous NAPL.
AB  - Thermal remediation techniques, such as hot water flooding, are emerging
      technologies that have been proposed for the removal of nonaqueous phase liquids
      (NAPLs) from the subsurface. In this study a combined laboratory and modeling
      investigation was conducted to determine if hot water flooding techniques would
      improve NAPL mass removal compared to ambient temperature water flushing. Two
      experiments were conducted in a bench scale two-dimensional sandbox (55 cmx45
      cmx1.3 cm) and NAPL saturations were quantified using a light transmission
      apparatus. In these immiscible displacement experiments the aqueous phase, at 22
      degrees C and 50 degrees C, displaced a zone with initial NAPL saturations on the
      order of 85%. The interfacial tension and viscosity of the selected light NAPL,
      Voltesso 35, are strongly temperature-dependent. Experimental results suggest
      that hot water flooding reduced the size of the high NAPL saturation zone, in
      comparison to the cold water flood, and yielded greater NAPL mass recovery (75%
      NAPL removal vs. 64%). Hot water flooding did not, however, result in lower
      residual NAPL saturations. A numerical simulator was modified to include
      simultaneous flow of water and organic phases, energy transport, temperature and
      pressure. Model predictions of mass removal and NAPL saturation profiles compared
      well with observed behavior. A sensitivity analysis indicates that the utility of
      hot water flooding improves with the increasing temperature dependence of NAPL
      hydraulic properties.

PMID- 17207893
TI  - Inhibition of PK/PBAN-mediated functions in insects: discovery of selective and
      non-selective inhibitors.
AB  - The antagonistic properties of a few linear and backbone cyclic (BBC)
      conformationally constraint peptide libraries and their analogs, were tested for
      the ability to inhibit pyrokinin/pheromone biosynthesis activating neuropeptide
      (PK/PBAN) mediated functions: sex pheromone biosynthesis in Heliothis peltigera
      female moths, cuticular melanization in Spodoptera littoralis larvae, pupariation
      in the fleshfly Neobellieria bullata and hindgut contraction in Leucophaea
      maderae, elicited by exogenously injected PBAN, pheromonotropin (PT),
      leucopyrokinin (LPK), myotropin (MT) or by the endogenous peptides. The data
      revealed differential inhibitory patterns within the same assay with different
      elicitors (in both the pheromonotropic and melanotropic assays) and among the
      different functions and disclosed selective antagonists, hinting at the
      possibility that the receptors that mediate those functions may differ from one
      another structurally.

PMID- 17207894
TI  - Regulation of hypothalamic NPY by diet and smoking.
AB  - Appetite is regulated by a number of hypothalamic neuropeptides including
      neuropeptide Y (NPY), a powerful feeding stimulator that responds to feeding
      status, and drugs such as nicotine and cannabis. There is debate regarding the
      extent of the influence of obesity on hypothalamic NPY. We measured hypothalamic
      NPY in male Sprague-Dawley rats after short or long term exposure to cafeteria
      style high fat diet (32% energy as fat) or laboratory chow (12% fat). Caloric
      intake and body weight were increased in the high fat diet group, and brown fat
      and white fat masses were significantly increased after 2 weeks. Hypothalamic NPY
      concentration was only significantly decreased after long term consumption of the
      high fat diet. Nicotine decreases food intake and body weight, with conflicting
      effects on hypothalamic NPY reported. Body weight, plasma hormones and brain NPY
      were investigated in male Balb/c mice exposed to cigarette smoke for 4 days, 4
      and 12 weeks. Food intake was significantly decreased by smoke exposure (2.32+/
      0.03g/24h versus 2.71+/-0.04g/24h in control mice (non-smoke exposed) at 12
      weeks). Relative to control mice, smoke exposure led to greater weight loss,
      while pair-feeding the equivalent amount of chow caused an intermediate weight
      loss. Chronic smoke exposure, but not pair-feeding, was associated with decreased
      hypothalamic NPY concentration, suggesting an inhibitory effect of cigarette
      smoking on brain NPY levels. Thus, consumption of a high fat diet and smoke
      exposure reprogram hypothalamic NPY. Reduced NPY may contribute to the anorexic
      effect of smoke exposure.

PMID- 17207895
TI  - Suppression of food intake by a complement C3a agonist [Trp5]-oryzatensin(5-9).
AB  - [Trp5]-oryzatensin(5-9) (WPLPR), an agonist peptide for complement C3a receptor,
      has been designed based on the C-terminal region of ileum-contracting peptide
      oryzatensin derived from rice protein. We previously reported that WPLPR has anti
      analgesic and anti-amnesic activities after central or oral administration. In
      this study, we found a novel function of WPLPR on food intake. WPLPR suppressed
      food intake after intracerebroventricular or intraperitoneal (i.p.)
      administration at a dose of 3-30 nmol/mouse or 30-300 mg/kg, respectively, in
      fasted mice. Orally administered WPLPR at a dose of 300 mg/kg also decreased food
      intake. WPLPR decreased gastric emptying after i.p. injection at a dose of 300
      mg/kg. The anorexigenic activity of WPLPR was blocked by cyclooxygenase inhibitor
      or antagonist for prostaglandin (PG) E receptor EP4 subtype. These results
      suggest that WPLPR decreases food intake through PGE2 production followed by EP4
      receptor activation.

PMID- 17207896
TI  - Neuropeptide Y regulates catecholamine release evoked by interleukin-1beta in
      mouse chromaffin cells.
AB  - Activation of the hypothalamic-pituitary-adrenal gland (HPA) axis can modulate
      the immune system. Cytokines and neuropeptide Y (NPY) are potent regulators of
      the HPA axis and are both produced by the adrenal medulla. The cytokine
      interleukin-1beta (IL-1beta) belongs to the interleukin-1 family along with
      interleukin-1alpha and the interleukin receptor antagonist (IL-1ra). The aim of
      the present study was to determine the interaction between NPY and IL-1beta in
      catecholamine (norepinephrine, NE and epinephrine, EP) release from mouse
      chromaffin cells in culture. We found that IL-1beta increased the constitutive
      release of NPY, NE and EP from mouse chromaffin cells. This IL-1beta stimulatory
      effect was blocked by IL-1ra. The immunoneutralization of NPY and the use of the
      NPY Y(1) receptor antagonist (BIBP 3226) inhibited the stimulatory effect of IL
      1beta on catecholamine release from these cells. The present work shows that IL
      1beta induces catecholamine release, and in turn this peptide will induce an
      additional increase in catecholamine release acting through the Y(1) receptor.
      This work suggests that NPY is involved in the regulatory loop between the immune
      and the adrenal system in some pathophysiological conditions where plasmatic IL
      1beta increases, like in sepsis, rheumatoid arthritis, stress or hypertension.

PMID- 17207897
TI  - Association between IL-8 cytokine and cognitive performance in an elderly general
      population--the MEMO-Study.
AB  - OBJECTIVES: To investigate the associations between circulating cytokines and
      specific neuropsychological domains of cognitive functioning (memory, processing
      speed and motor function) and general cognitive function (MMSE) in healthy
      elderly individuals. METHODS: In a cross-sectional study of 369 community
      dwelling elderly subjects, we examined the relationship between serum IL-1beta,
      sIL-4R, IL-6, IL-8, IL-10, IL-12 and TNF-alpha concentrations and cognitive
      performance using an extensive standardized and validated cognitive test battery
      assessing memory, word fluency, perceptual/cognitive speed, attention and
      executive functioning, and motor speed. RESULTS: Multivariate analysis adjusted
      for various confounders and Bonferroni correction for multiple comparisons
      demonstrated that increased serum concentrations of IL-8 were associated with
      poor performance in the memory and speed domains and in motor function. No
      significant associations were found between the remaining cytokines and domains
      of cognitive functioning. Global cognitive functioning, as measured with MMSE,
      was not associated with any cytokine. CONCLUSIONS: This study suggests an
      association between circulating IL-8 concentrations and cognitive dysfunction in
      the elderly. An interaction between this cytokine and glial cells may help
      explain the pathophysiological mechanisms leading to cognitive impairment in our
      study group.

PMID- 17207898
TI  - Olfaction in patients with mild cognitive impairment and Alzheimer's disease.
AB  - Understanding of olfactory dysfunction in Alzheimer's disease (AD) remains
      limited. In particular, it is not known how early in the course of the disease
      olfactory deficits occur, and whether they are restricted to identification or
      involve other aspects of olfaction. We studied olfactory (odor detection
      thresholds, quality discrimination, and identification) and cognitive (attention,
      reasoning, memory, naming and fluency) functioning in patients with AD, with mild
      cognitive impairment (MCI), and in normal elderly control (NEC) participants. MCI
      patients were impaired in olfactory sensitivity and identification, while a
      discrimination deficit was accounted for by abnormal thresholds. AD patients were
      impaired in all three domains, and were worse than the MCI group. Odor
      discrimination (OD) and identification performance correlated more prominently
      than detection thresholds with performance on neuropsychological tests. We
      concluded that deficits in olfactory detection thresholds and identification
      occur early in AD, before clinical symptoms are fully developed, and decline
      further over the course of the disease. High detection thresholds, together with
      impaired identification, may be useful as an early indicator of AD.

PMID- 17207899
TI  - Neural substrates for episodic encoding and recognition of unfamiliar faces.
AB  - Functional MRI was used to investigate brain activation in healthy volunteers
      during encoding of unfamiliar faces as well as during correct recognition of
      newly learned faces (CR) compared to correct identification of distractor faces
      (CF), missed alarms (not recognizing previously presented faces, MA), and false
      alarms (incorrectly recognizing newly presented faces, FA). Encoding was
      associated with frontal, occipital/fusiform, thalamic, and cerebellar activation.
      CR produced activation in frontal and cerebellar regions, whereas CF activated
      frontal and occipitotemporal regions as well as the thalamus. In contrast, MA was
      associated with frontal and thalamic activation, and FA with frontal activation.
      The CR minus CF comparison showed left lateral prefrontal and parietal
      activation, while no suprathreshold positive signal changes were detected when
      subtracting the other conditions (CR minus MA, CR minus FA, and vice versa).
      These results support the view that the successful episodic retrieval of newly
      learned faces is based on a dorsal visual stream mechanism.

PMID- 17207900
TI  - The dilemma of approving antidotes.
AB  - Clinical trials with antidotes are difficult to perform for a variety of
      practical, ethical, and financial reasons. As acute poisoning is a rare event,
      the commercial interest in basic and clinical research is low. Poisoned patients
      are usually not available for normal clinical trial procedures and, if they are,
      they cannot give informed consent. This situation results in a dilemma: antidotes
      are essential drugs. A resolution of the Council of Europe requests to guarantee
      the optimal availability of antidotes and the improvement of their use. As
      comprehensive data on the efficacy of antidotes are often missing, a marketing
      authorisation under exceptional circumstances according to Article 14(8) of
      Regulation (EC) No. 276/2004, will often be the only way to get an approval, as:
      (1) the indications for which the product in question is intended are encountered
      so rarely that the applicant cannot reasonably be expected to provide
      comprehensive evidence ("orphan drug"), (2) in the present state of scientific
      knowledge, comprehensive information cannot be provided, or (3) it would be
      contrary to generally accepted principles of medical ethics to collect such data.
      Typically, data on antidotes are obtained from a patchwork of studies with
      animals, human tissue and a few observations from human poisoning corroborated
      with data from clinical observations and biochemistry. Generalisations from
      chemical and mechanistic similarities between groups of poisons are usual, but
      often lack scientific evidence. Current standards of good clinical practice can
      rarely be observed. Therefore, public funding and other financial support are
      necessary incentives to initiate trials in this important area.

PMID- 17207901
TI  - Risk of preterm delivery in relation to vaginal bleeding in early pregnancy.
AB  - OBJECTIVE: To examine the relationship between vaginal bleeding during early
      pregnancy and preterm delivery. METHODS: Study subjects (N=2678) provided
      information regarding socio-demographic, biomedical, and lifestyle
      characteristics. Logistic regression was used to estimate odds ratios (OR) and
      95% confidence intervals (95% CI). RESULTS: Any vaginal bleeding in early
      pregnancy was associated with a 1.57-fold increased risk of preterm delivery (95%
      CI: 1.16-2.11). Vaginal bleeding was most strongly related with spontaneous
      preterm labor (OR=2.10) and weakly associated with preterm premature rupture of
      membrane (OR=1.36) and medically induced preterm delivery (OR=1.32). As compared
      to women with no bleeding, those who bled during the first and second trimesters
      had a 6.24-fold increased risk of spontaneous preterm labor; and 2-3-fold
      increased risk of medically induced preterm delivery and preterm premature
      rupture of membrane, respectively. CONCLUSION: Vaginal bleeding, particularly
      bleeding that persists across the first two trimesters, is associated with an
      increased risk of preterm delivery.

PMID- 17207902
TI  - Agreement among insulin sensitivity indexes on the diagnosis of insulin
      resistance in polycystic ovary syndrome and ovulatory women.
AB  - OBJECTIVE: The objective was to compare agreement on the diagnosis of insulin
      resistance (IR) among insulin sensitivity indexes in both ovulatory women and
      those with polycystic ovary syndrome (PCOS). STUDY DESIGN: In an observational
      study, the 75-g oral glucose tolerance test was performed in 105 women with PCOS
      and 51 ovulatory women. The insulin sensitivity indexes used were insulin
      quantitative sensitivity check index (QUICKI), 1/homeostasis model assessment
      insulin resistance (1/HOMA-IR), area under curve for insulin (AUC-I), and the
      Matsuda insulin sensitivity index (COMP). For the IR diagnosis we used cut-off
      values described in recent publications (insulin >12 microIU/ml, 1/HOMA-IR <0.47,
      QUICKI < or =0.333, AUC-I > or =7000 microIU/ml 120 min, and COMP <4.75. RESULTS:
      Excellent agreement was assessed among insulin, QUICKI, and 1/HOMA-IR. However,
      the rate of IR detected by these indexes in the PCOS group (44.8-51.4%) was lower
      than expected. New cut-offs were then determined based on COMP results. Using
      these values, 1/HOMA-IR and QUICKI showed excellent agreement (kappa=0.83) with
      COMP. CONCLUSION: The observed agreements among insulin, QUICKI and 1/HOMA-IR
      were higher than 93%. Therefore, clinicians may choose any of those obtaining
      similar results. For clinicians who prefer COMP, but are looking for a simpler
      test to detect IR in PCOS women, the use of QUICKI and 1/HOMA-IR with the new cut
      offs seems reasonable.

PMID- 17207903
TI  - Feasibility and reliability of strain and strain rate measurement in neonates by
      optimizing the analysis parameters settings.
AB  - The optimal combination of region-of-interest (ROI) size and strain length (SL)
      allowing two-segment strain and strain rate analyses in term neonates was
      investigated. The impact of different ROI sizes and SLs on the strain and strain
      rate beat-to-beat variation (BBV) was assessed in 80 good-quality tissue velocity
      images. Both BBVs decreased with increased ROI length and with increased SL (p <
      0.05). There were no significant differences in the BBVs for ROI width 2, 3 and 4
      mm (p > 0.05). Among the combinations eligible for two segment analysis, the
      lowest BBVs were found using SL 10 mm, ROI length 1 mm and ROI width 3 mm. Using
      this combination, the mean difference between the single-cycle value and two
      cycle compound value for peak systolic strain rate was 6.2%, peak systolic strain
      was 2.9% and end systolic strain was 3.2% of the two-cycle compound mean values.
      Hence, strain and strain rate measurement in tissue velocity images in neonates
      is feasible and reliable.

PMID- 17207904
TI  - Changes of contrast-specific ultrasonic cerebral perfusion patterns in the course
      of stroke; reliability of region-wise and parametric imaging analysis.
AB  - Ultrasound perfusion imaging (UPI) reliably detects size and localization of
      acute stroke. It remains unclear which time window detects, most sensitively and
      specifically, early changes of cerebral perfusion patterns and whether region
      wise analysis is superior to parametric imaging analysis. Bilateral phase
      inversion harmonic imaging examinations (bolus kinetic, fitted model function)
      were performed twice (acutely and 28 h later) in 10 patients with acute ischemic
      stroke (<12 h). Examinations were evaluated using a region-wise analysis of the
      time-intensity curve and by parametric images of the time-to-peak intensity maps.
      Results were correlated in-between the ultrasound examinations and to follow-up
      cranial computed tomography (CCT) scans. Correlation between the early region
      wise UPI examination and follow-up CCT was the strongest (Spearman correlation
      coefficient 0.76, sensitivity 84%, specificity 96%). Spearman coefficient between
      the late UPI examination and CCT was 0.51; sensitivity and specificity were 71%
      and 82%. Values in between UPI examinations were 57% and 88%, with a Spearman
      coefficient of 0.47 (p for all < 0.001). Values of the analysis of the parametric
      images were less strong. Concordance between both of the UPI methods was 65% in
      the early examination and 72% in the late examination. Changes of perfusion
      patterns are most accurately detected in the early course of stroke, when core of
      infarction can be differentiated from penumbra and viable tissue. Reperfusion
      phenomena may impair the diagnostic impact in later examinations. Parametric
      imaging does not yet seem to be as accurate as region-wise analysis.

PMID- 17207905
TI  - Therapeutic ultrasound effects on interleukin-1beta stimulated cartilage
      construct in vitro.
AB  - A low-intensity ultrasound (LIUS) was examined for its possible therapeutic
      effects on degenerative osteoarthritic cartilage. Along with the daily treatment
      of 5 ng interleukin-1beta (IL-1beta) for 5 d, an engineered 3D neocartilage
      construct was used as an in vitro OA model. Followed by 24 h preincubation with
      the first dose of IL-1beta, the constructs were then given ultrasonic stimulation
      (frequency 1.5 MHz and SATA 30 mW/cm(2)) once a day up to 5 d for the
      predetermined time. Fresh IL-1beta was added before the stimulation. The
      difference in the cell number and viability was insignificant between control (US
      /IL+) and LIUS-stimulated groups. As the daily stimulation time was extended, the
      GAG contents in the constructs themselves significantly increased with 50 min
      stimulation but those released into the culture medium remained unaffected by
      LIUS. While the gene expression level of aggrecan was similar between control and
      LIUS (50 min) group, the ratio of collagen type II to type I was found to be
      higher in the control. The mRNA level of matrix metalloproteinase (MMP)-1 was
      substantially downregulated in the stimulated construct and that of MMP-13 was
      indifferent between control and stimulated one. The endogenous expression of
      transforming growth factor (TGF)-beta1 and beta3 was barely responsive to the
      LIUS stimulation. From histologic analysis, more intense GAG deposition was
      clearly identified with the LIUS-stimulated constructs. This study indicates that
      LIUS may have a significant potential to be a chondroprotective stimulant for
      osteoarthritic cartilage.

PMID- 17207906
TI  - Color Doppler US pulmonary artery vessel signal: a sign for predicting the benign
      lesions.
AB  - The lung cancer blood supply originates from the bronchial artery. If vessel
      signals within pulmonary lesions can be confirmed to be those of the pulmonary
      artery, color Doppler ultrasound (US) should be able to predict and differentiate
      benign lesions from lung cancers. Two hundred sixty-four patients with abutting
      thoracic lesions (including 125 lung cancers and 139 benign lesions) underwent
      color Doppler US examinations. A pulsatile flow, with the vessel signal length on
      sonographic appearance > or =1 cm demonstrated by color Doppler US, was
      arbitrarily defined as a pulmonary artery vessel signal. Of the 264 thoracic
      lesions, 73 (58%) lung cancers and 107 (77%) benign lesions had detectable color
      Doppler US pulsatile flow vessel signals. Analyzing the pulsatile flow vessel
      signals, the color Doppler US pulmonary artery vessel signal was present in 74
      (53%) benign lesions, but was found in only two (2%) lung cancers of a specific
      alveolar cell carcinoma with lobar consolidation. Using the pulmonary artery
      vessel signal, color Doppler US can be valuable in predicting and differentiating
      benign lesions from lung cancers (p < 0.0001, sensitivity = 0.53, specificity =
      0.98 and positive likelihood ratio 26.5). In conclusion, color Doppler US
      pulmonary artery vessel signal sign is useful in predicting and differentiating
      benign lesions from lung cancers.

PMID- 17207907
TI  - Phagocytosis of ultrasound contrast agent microbubbles by Kupffer cells.
AB  - Delayed parenchymal phase images of the liver more than 5 min after IV injection
      of ultrasound contrast agents are thought to be related to the phagocytosis of
      contrast agent microbubbles by macrophages. In this study, we examined whether
      liver-specific macrophages, Kupffer cells, phagocytosed the microbubbles and
      whether their elimination affected the delayed parenchymal images of the liver.
      Phase-contrast microscope observations showed that Kupffer cells phagocytosed
      various contrast agents in vitro. Among the contrast agents used, 99% of Sonazoid
      and Optison, and 47% of Levovist were phagocytosed, whereas only 7.3% of SonoVue
      and 0% of Imavist were phagocytosed. Elimination of Kupffer cells in vivo by
      gadolinium chloride (GdCl(3)) resulted in decreased intensity of the delayed
      parenchymal images with Sonazoid and Levovist, while SonoVue showed no changes
      compared with control. Our findings suggested that Kupffer cells phagocytosed
      contrast agents and they were responsible for the delayed images of contrast
      ultrasound in the liver.

PMID- 17207908
TI  - A single procalcitonin level does not predict adverse outcomes of women with
      pyelonephritis.
AB  - OBJECTIVES: Predicting medical outcomes for pyelonephritis in women is difficult,
      leading to unnecessary hospitalization. Unlike other serious infectious diseases,
      high procalcitonin (PCT) level has never been associated with 28-d adverse
      medical outcomes in women with pyelonephritis. Therefore, we sought to determine
      the accuracy of PCT in discriminating between pyelonephritis with adverse medical
      outcome (PAMO) and pyelonephritis without adverse medical outcome (PWAMO).
      PATIENTS AND METHODS: Adult women with pyelonephritis presenting to the emergency
      department of a French tertiary care hospital were consecutively included. Those
      patients who developed adverse medical outcomes during a 28-d follow-up period
      were identified as having PAMO. Baseline characteristics and PCT level were
      compared between patients with PAMO and PWAMO. RESULTS: Eleven women (19.0%) had
      PAMO and 47 (81%) had PWAMO. The median PCT level was higher in PAMO compared
      with PWAMO 0.51 ng/ml (IQR: 0.04-3.8) and 0.08 ng/ml (IQR: 0.01-1.0), but this
      difference was not statistically significant (p=0.07). We failed to find a
      threshold value for PCT that discriminated between PAMO and PWAMO (ROC, AUC=0.67
      [95%CI, 0.51-0.86]). All but one subject with PAMO had either a PCT level >0.1
      ng/ml or an underlying genitourinary abnormality by radiographic testing.
      CONCLUSIONS: A single PCT level was a poor predictor of 28-d adverse medical
      outcomes in women with pyelonephritis treated in the emergency department.
      Prediction based on underlying genitourinary abnormality by radiographic testing
      in addition to the PCT level should be investigated in future studies.

PMID- 17207909
TI  - Renal cell carcinoma with nodal metastases in the absence of distant metastatic
      disease: prognostic indicators of disease-specific survival.
AB  - OBJECTIVES: Outcome of patients with exclusive renal cell carcinoma (RCC) nodal
      metastases without distant metastases is not extensively described. We explored
      the ability of standard risk factors such as tumour size, Fuhrman grade,
      histologic subtype and symptom classification to predict renal cell carcinoma
      specific survival (RCC-SS). METHODS: Analyses targeted 171 patients with RCC
      nodal metastases and absence of distant metastases. Univariable, multivariable,
      and predictive accuracy analyses addressed RCC-SS with the intent of identifying
      independent and most informative predictors of RCC-SS in this cohort of patients.
      RESULTS: Median RCC-SS was 2.3 yr. Symptom classification (61.3%, p<0.001)
      demonstrated the highest univariable accuracy. In multivariable analyses, symptom
      classification contributed the most to the combined predictive accuracy of all
      variables (+4.2%, p<0.001), followed by Fuhrman grade (+2.3%) and histologic
      subtype (+1.0%). CONCLUSIONS: Renal cell carcinoma-specific survival of patients
      with exclusive nodal metastases may show important variability. In presence of
      systemic symptoms, survival is extremely poor. Substantially better survival may
      be expected in patients with local or no symptoms. This observation has important
      implications when adjuvant therapies are considered.

PMID- 17207910
TI  - Diagnostic accuracy of noninvasive tests to evaluate bladder outlet obstruction
      in men: detrusor wall thickness, uroflowmetry, postvoid residual urine, and
      prostate volume.
AB  - OBJECTIVES: The aim of this prospective study was to compare the diagnostic
      accuracy of detrusor wall thickness (DWT), free uroflowmetry, postvoid residual
      urine, and prostate volume (index tests) with pressure-flow studies (reference
      standard) to detect bladder outlet obstruction (BOO) in men. METHODS: During a 2
      yr period, men older than 40 yr with lower urinary tract symptoms and/or
      prostatic enlargement had the following tests: ultrasound measurements of DWT,
      free uroflowmetry (Q(max), Q(ave)), postvoid residual urine, and prostate volume.
      Pressure-flow studies were used to divide obstructed from nonobstructed bladders.
      RESULTS: One hundred sixty men between 40-89 yr of age (median: 62 yr) were
      included in the study; 75 patients (46.9%) had BOO according to pressure-flow
      studies. The results of all investigated index tests differed significantly
      between obstructed and nonobstructed men. DWT was the most accurate test to
      determine BOO: the positive predictive value was 94%, specificity 95%, and the
      area under the curve of ROC analysis 0.93. There was an agreement of 89% between
      the results of DWT measurement and pressure-flow studies. CONCLUSIONS:
      Measurements of DWT can detect BOO better than free uroflowmetry, postvoid
      residual urine, or prostate volume. In clinical routine, DWT measurements can be
      used to judge BOO noninvasively.

PMID- 17207911
TI  - Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line
      chemotherapy in advanced transitional cell carcinoma of the urothelium: results
      of a randomized phase 2 trial.
AB  - OBJECTIVES: This phase 2 randomized study compared the toxicity and assessed the
      efficacy of gemcitabine-cisplatin (GP) and gemcitabine-carboplatin (GC) in
      patients with advanced transitional cell carcinoma of the urothelium (TCC), with
      the main objective to demonstrate a reduction in toxicity of at least 25% in the
      GC arm. METHODS: A total of 110 chemonaive patients (55 per arm) with locally
      advanced or metastatic TCC received gemcitabine 1250 mg/m(2) on days 1 and 8 plus
      cisplatin 70 mg/m(2) on day 2 (GP) every 3 wk or gemcitabine 1250 mg/m(2) on days
      1 and 8 plus carboplatin AUC 5 on day 2 (GC) every 3 wk for a maximum of six
      cycles. RESULTS: No differences between arms were noted in the overall toxicity
      profiles and any parameter of toxicity. The most frequent grade 3-4 hematologic
      toxicity was neutropenia in 34.6% of patients for GP and 45.4% for GC. The most
      frequent grade 3-4 nonhematologic toxicity was nausea and vomiting (GP: 9.1%; GC:
      3.6%). Grade 1-2 nephrotoxicity occurred in 14 GP-treated patients (26.0%) and 9
      GC-treated patients (16.3%). Per an intent-to-treat analysis, overall response,
      evaluated on 80 patients, was 49.1% for GP (CR: 14.5%; PR: 34.5%) and 40.0% for
      GC (CR: 1.8%; PR: 38.2%). Median time to progression was 8.3 mo for GP and 7.7 mo
      for GC. Median survival was 12.8 mo and 9.8 mo for GP and GC, respectively.
      CONCLUSIONS: GC has a comparably acceptable toxicity profile compared with that
      of GP and seems active in patients with TCC.

PMID- 17207912
TI  - Urinary CYFRA 21.1 is not a useful marker for the detection of recurrences in the
      follow-up of superficial bladder cancer.
AB  - OBJECTIVES: The objective of this prospective study is to establish an
      appropriate cutoff value of urinary CYFRA 21.1 assay and to assess its utility
      combined with voided cytology and/or haemoglobin dipstick in the follow-up of
      patients with superficial bladder cancer. METHODS: From December 2000 to November
      2003, 446 patients in follow-up for superficial bladder cancer (Ta-T1) after
      transurethral resection of the bladder (TURB) were included in a prospective
      study. Voided urine specimens were collected 7-14 d before cystoscopy and/or TURB
      for CYFRA 21.1 (one sample), haemoglobin dipstick (one sample), and cytology
      (three samples). All samples were processed for CYFRA 21.1 and haemoglobin
      dipstick according to manufacturer instructions. A control group (n=185) was
      obtained from patients in follow-up after transurethral resection of superficial
      disease (without recurrences within the following 6 mo). There were 125 recurrent
      transitional tumours detected by cystoscopy (34 TaG1; 53 TaG2/T1G1-2; 23 Ta
      1G3/Tis, and 15 T2-4). Receiver operator characteristic (ROC) curves were
      constructed and cutoff values were chosen. Sensitivity, specificity, PPV
      (positive predictive value), NPV (negative predictive value), and their 95%
      confidence intervals were calculated. RESULTS: ROC curve analysis based on the
      previously reported cutoff value of 4ng/ml for CYFRA 21.1 demonstrated a
      sensitivity and specificity of 43% and 68%, respectively. At a cutoff value of
      1.5ng/ml, sensitivity was 73.8% with a low specificity (41%). Further lowering of
      the cutoff point below 1.5ng/ml did not demonstrate a significant increase in
      sensitivity. Therefore, this value was chosen as the most sensitive CYFRA 21.1
      cutoff point during the rest of the study. Specificity increased when all the
      patients treated with pelvic radiotherapy or with UTI, urethral catheterisation,
      and intravesical instillations within 3 previous months were not included in our
      analysis. CYFRA 21.1 plus cytology and the combination of CYFRA 21.1, cytology,
      and haemoglobin dipstick demonstrated the highest overall sensitivities, and
      detected 91.3% of Ta-1G3 tumours and 93.3% of T2-4 tumours. However, there were
      one muscle-invasive tumour, two T1G3/Tis, three T1G2, and nine T1G1 neoplasms
      with negative combination of cytology and CYFRA 21.1 (1,5ng/ml). All these
      tumours were smaller than 2cm in size; most were single tumours. Nevertheless,
      there were 16 tumours larger than 0.5cm (0.5-2cm), and multiple neoplasms were
      endoscopically detected in 14 patients. Similar results were obtained through the
      combination of CYFRA 21.1 (cutoff: 1.5ng/ml), cytology, and haemoglobin dipstick.
      CONCLUSIONS: In our experience the low sensitivity of urinary CYFRA 21.1, even
      using lower cutoff values and/or a combination with cytology and/or haemoglobin
      dipstick, makes its application not very useful as a surveillance tool for
      superficial bladder carcinoma.

PMID- 17207913
TI  - Small intestinal submucosa (SIS) graft urethroplasty: short-term results.
AB  - OBJECTIVE: We evaluated the use of small intestinal submucosa (SIS) graft in
      penile and bulbar urethroplasties. METHODS: From 2003 to 2004, 20 men (mean age,
      41 yr) with anterior urethral strictures underwent urethroplasty using SIS (COOK)
      as an inlay or onlay patch graft. Stricture location was penile in 1 patient,
      bulbar in 16, and penile-bulbar in 3. Average stricture and graft lengths were 3
      and 5.7 cm, respectively. A dorsal inlay graft was performed in 14 cases, ventral
      onlay graft in 1, and dorsal inlay plus ventral onlay in 5. Clinical outcome was
      considered successful if no postoperative procedure was needed. RESULTS: Mean
      follow-up period was 21 mo (range: 13-35 mo). Seventeen cases (85%) were
      successful and 3 (15%) were failures. No postoperative complications were related
      to the use of heterologous graft material, such as infection or rejection.
      Sixteen successes (94%) were bulbar repairs and one a penile-bulbar repair, with
      stricture and graft average lengths 2.6 and 5.35 cm, respectively. Cystoscopy at
      3 mo revealed adequate calibre lumens, but SIS grafted areas were not completely
      replaced by urothelium. The three failures were penile and penile-bulbar urethral
      repairs with stricture and graft average lengths of 5.7 and 7.7 cm, respectively.
      Recurrences showed fibrous tissue involving the grafted area with extension into
      the penile and bulbar urethra. CONCLUSIONS: In our short-term results, SIS seems
      to be a versatile material that may have a role in select urethral
      reconstructions. Longer follow-up and further investigations in select patients
      are needed before widespread use is advocated.

PMID- 17207914
TI  - Expression of matrix metalloproteinase-10 in renal cell carcinoma and its
      prognostic role.
AB  - OBJECTIVES: Matrix metalloproteinase (MMP)-10 is associated with malignant
      aggressiveness in various cancers, but its importance has not been investigated
      in conventional renal cell carcinoma (CRCC). The purpose of this study was to
      determine the clinical significance and malignant potential of MMP-10 in human
      CRCC tissues. PATIENTS AND METHODS: Specimens were obtained from 103 CRCC
      patients who underwent radical surgery and were examined by immunohistochemistry
      for MMP-10 expression. The proportions of Ki-67-stained cells (proliferation
      index: PI) and densities of CD34-positive vessels (microvessel density: MVD) were
      measured by a computer-aided image analysis system. The relationships between MMP
      10 expression and clinicopathologic features and various parameters including
      tumour size, PI, MVD, and survival were investigated by univariate and
      multivariate analyses. RESULTS: MMP-10 expression was mainly detected in cancer
      cell cytoplasm, and 45 (43.7%) CRCCs were considered MMP-10-positive. MMP-10
      expression correlated with grade (p=0.006) and pT stage (p<0.001), and it was a
      significant and independent factor for high pT stage in multivariate analysis
      model. MMP-10 expression was associated with MVD (p = 0.022) but not tumour size
      or PI. MMP-10 expression in CRCC was a significant predictor of poor outcome by
      log-rank test (p = 0.013) but not by multivariate analysis. CONCLUSIONS: MMP-10
      seems to play an important role in renal cancer cell invasion and is a
      potentially useful therapeutic target to prevent CRCC tumour progression.

PMID- 17207915
TI  - Pelvis architecture and urinary incontinence in women.
AB  - OBJECTIVES: To examine anatomic features in the pelvic bones and muscles in women
      with urinary incontinence (UI). MATERIAL AND METHODS: Between October 2005 and
      January 2006, 212 consecutive women underwent pelvic computerized tomography in
      our center. Preceding the examination, all women completed a clinical and
      demographic questionnaire including detailed questions about UI. Several anatomic
      parameters using multiplanar reformation and three-dimensional techniques (volume
      rendering) were examined. We specifically evaluated different bony parameters,
      pelvic floor muscle angles, densities, and cross-sectional areas. Ninety-three
      women (46.5%) had UI; the remaining women served as the control group. A logistic
      regression model was used to evaluate risk factors for UI. RESULTS: The mean age
      was 55.5 yr (range: 19-90). Women who suffered from UI were older (60.97 vs.
      50.77 yr, p<0.0001), had higher body mass index (27.65 vs. 25.49, p<0.01), had
      more previous hysterectomies (21.5% vs. 6.5%, p<0.005), underwent more pelvic
      irradiation (9.7% vs. 1.8%, p<0.05), and had more diabetes mellitus (31.2% vs.
      13.1%, p<0.005). Patient's age and previous hysterectomy were found to be the
      major clinical risk factors for UI (OR: 1.029, p=0.002; OR: 2.94, p=0.024,
      respectively). Logistic regression analysis on all clinical and morphologic
      variables yielded the following risk factors: pelvic-inlet diameter (OR: 1.216,
      p<0.0001), pelvic-inlet anterior-posterior diameter (OR: 1.109, p=0.003), pelvic
      outlet diameter (OR: 1.077, p=0.011) and transverse perineal muscle cross-section
      diameter (OR: 0.773, p<0.0001). CONCLUSIONS: Pelvic inlet and outlet dimensions
      are major risk factors for developing UI in women. These findings may lead to a
      better comprehension of the pathophysiology of UI in women.

PMID- 17207916
TI  - Vacuum-assisted closure versus conventional wound care in the treatment of wound
      failures following inguinal lymphadenectomy for penile cancer: a retrospective
      study.
AB  - OBJECTIVES: Impaired wound healing is a frequent event in inguinal surgery and
      very common after lymphadenectomy for penile cancer. Although vacuum therapy has
      been reported to expedite the healing of complex wound failures, vacuum-assisted
      closure (VAC) has been reported to be contraindicated in malignancy. In the
      present study we evaluated the use of VAC in the treatment of complex wound
      failures following inguinal lymphadenectomy for penile cancer in comparison to
      conventional wound care (CWC) implying debridement and saline-soaked gauze.
      METHODS: We retrospectively identified six inguinal wounds following inguinal
      lymphadenectomy for penile cancer and subsequent use of VAC from 2003 to 2006 at
      our institution. Data on surgical interventions, complications, length of time
      required for closure, and outcome were compared to 10 inguinal defects treated
      with CWC between 2000 and 2003. RESULTS: Wound volume was comparable for both
      groups. Wound breakdown occurred at a median of 7.4 d after inguinal
      lymphadenectomy and was treated by CWC for a mean of 69.8 d. In the VAC group,
      the median duration until complete closure was 38.9 d. Thus, VAC was shown to
      result in complete wound healing in less time (p<0.001). No local recurrence in
      the VAC group was noted despite positive lymph nodes. CONCLUSIONS: VAC therapy is
      effective in complex inguinal wound failures following lymphadenectomy for penile
      cancer and appears to be superior to CWC. VAC seems to offer adequate safety
      concerning local recurrence.

PMID- 17207917
TI  - Editorial comment on: diagnostic accuracy of noninvasive tests to evaluate
      bladder outlet obstruction in men: detrusor wall thickness, uroflowmetry,
      postvoid residual urine, and prostate volume.

PMID- 17207918
TI  - A Wiener-type neuronal model in the presence of exponential refractoriness.
AB  - An instantaneous return process in the presence of random refractoriness for
      Wiener model of single neuron activity is considered. The case of exponential
      distributed refractoriness is analyzed and expressions for output distributions
      and interspike intervals density are obtained in closed form. A computational
      study is performed to elucidate the role played by the model parameters in
      affecting the firing probabilities and the interspike distribution.

PMID- 17207919
TI  - Cyclins, cyclin dependent kinases, and regulation of steroid receptor action.
AB  - Steroid receptors (SR), which are ligand activated transcription factors, and
      their coactivators are phosphoproteins whose activities are regulated by cell
      signaling pathways. Many of the identified phosphorylation sites in these
      proteins contain Ser/Thr-Pro motifs suggesting that they are substrates for
      cyclin dependent kinases and/or for mitogen activated protein kinases. An
      analysis of the roles of cyclins and their kinases in regulating receptor action
      has revealed that there are both stimulatory and inhibitory actions of cyclins,
      that some of the actions are independent of the partner kinases and that these
      activities are receptor specific. Consistent with this finding, the limited
      analyses of receptor activity as a function of cell cycle reveal distinct
      patterns of activation. SR often regulate cell proliferation. Thus, the cross
      talk between cyclins and their kinases and the SR provides a means for
      integrating the actions of the SR with the cell cycle status of cells.

PMID- 17207920
TI  - A genome-wide assessment of adrenocorticotropin action in the Y1 mouse adrenal
      tumor cell line.
AB  - This report summarizes the genome-wide effects of ACTH on transcript accumulation
      in mouse adrenal Y1 cells and the relative contributions of the cAMP-, protein
      kinase C- and Ca(2+)-dependent signaling pathways to these actions of the
      hormone. ACTH affected the accumulation of 1386 transcripts, a much larger number
      than previously appreciated. The cAMP signaling pathway accounted for
      approximately 56% of the ACTH effects whereas the protein kinase C- and Ca(2+)
      dependent pathways made smaller contributions to ACTH action. Approximately 38%
      of the ACTH-affected transcripts could not be assigned to these signaling
      pathways and thus represent candidates for regulation via other mechanisms. The
      set of ACTH-regulated transcripts included clusters with functions in steroid
      metabolism, cell proliferation and alternative splicing. Collectively, our
      results suggest that Y1 adrenal cells undergo extensive remodeling upon prolonged
      stimulation with ACTH. The functional implications of ACTH on alternative
      splicing are explored.

PMID- 17207921
TI  - GATA transcription factors in adrenal development and tumors.
AB  - Of the six GATA transcription factors, GATA-4 and GATA-6 are expressed in the
      mouse and human adrenal with distinct developmental profiles. GATA-4 is confined
      to the fetal cortex, i.e. to the less differentiated proliferating cells, while
      GATA-6 is expressed both in the fetal and adult adrenal. In vitro, GATA-4
      regulates inhibin-alpha and steroidogenic factor-1 implicated in normal adrenal
      function. GATA-6 probably has roles in the development and differentiation of
      adrenocortical cells, and in the regulation of steroidogenesis. GATA-4 expression
      is dramatically upregulated and GATA-6 downregulated in gonadotropin dependent
      mouse adrenocortical tumors. This is accompanied by the appearance of luteinizing
      hormone receptor (LHR). In vitro, GATA-4 transactivates LHR promoter, and
      gonadotropins upregulate GATA-4 levels. Human adrenal tumors occasionally express
      GATA-4, whereas GATA-6 levels are usually lower than normal.

PMID- 17207922
TI  - Enzymes involved in arachidonic acid release in adrenal and Leydig cells.
AB  - Stimulation of receptors and subsequent signal transduction results in the
      activation of arachidonic acid (AA) release. Once AA is released from
      phospholipids or others esters, it may be metabolized via the cycloxygenase or
      the lipoxygenase pathways. How the cells drive AA to these pathways is not
      elucidated yet. It is reasonable to speculate that each pathway will have
      different sources of free AA triggered by different signal transduction pathways.
      Several reports have shown that AA and its lipoxygenase-catalyzed metabolites
      play essential roles in the regulation of steroidogenesis by influencing
      cholesterol transport from the outer to the inner mitochondrial membrane, the
      rate-limiting step in steroid hormone biosynthesis. Signals that stimulate
      steroidogenesis also cause the release of AA from phospholipids or other esters
      by mechanisms that are not fully understood. This review focuses on the enzymes
      of AA release that impact on steroidogenesis.

PMID- 17207923
TI  - Tyrosine phosphatases in steroidogenic cells: regulation and function.
AB  - In adrenocortical and Leydig cells PKA activation by trophic hormones increases
      the activity of protein tyrosine phosphatases and also induces the expression of
      MAP kinase phosphatase 1 (MKP-1), a dual activity protein phosphatase
      (serine/threonine and tyrosine). This work summarizes the knowledge on the
      regulation and the role played by cAMP-activated tyrosine phosphatases as well as
      MKP-1 in the hormonal activation of the acute and chronic phases of
      steroidogenesis.

PMID- 17207924
TI  - Mechanism of StAR's regulation of mitochondrial cholesterol import.
AB  - The steroidogenic acute regulatory protein (StAR) mediates the acute
      steroidogenic response by moving cholesterol from the outer to inner
      mitochondrial membrane, but the mechanism of StAR's action has remained
      mysterious. We showed that StAR acts on the outer membrane, requires cholesterol
      binding, and requires the structural change previously described as a pH
      dependent molten globule. The current model is that StAR's interaction with
      protonated phospholipid head groups on the outer mitochondrial membrane induces a
      molten globule transition needed for StAR to take up cholesterol. Recent data
      suggest a functional interaction between StAR and the peripheral benzodiazepine
      receptor (PBR). Whereas many models have suggested that StAR delivers cholesterol
      to PBR, we suggest that StAR removes cholesterol from the cholesterol-binding
      domain of PBR and delivers it to the inner mitochondrial membrane.

PMID- 17207925
TI  - CT angiography demonstration of the development of intraventricular hemorrhage
      during aneurysm rupture.
AB  - The authors present the 3D reconstructed CT angiography image of extravasation
      from a rebleeding aneurysm. Direct hemorrhage of a bleeding aneurysm into the
      lateral ventricle was detected by CT angiography. This image clearly visualized
      that extravasated contrast medium spurting from a rupturing anterior
      communicating artery aneurysm, penetrated the ventricle wall and passed through
      the lateral ventricle to reach the temporal horn. This case provides a real-time
      demonstration of the way how an intraventricular hemorrhage develops during
      rupture of an anterior communicating artery aneurysm.

PMID- 17207926
TI  - Galectins - potential targets for cancer therapy.
AB  - Galectins are a family of galactose binding lectins that have become the focus of
      attention of cancer biologists due to their numerous regulatory roles in normal
      cellular metabolism and also because of their altered levels in various cancers.
      They are reportedly similar to several prominent and established modulators of
      apoptosis. In this review, we present a brief outline of the advancements in the
      methodology used to detect and identify them and their therapeutic applications
      in cancer. Their possible interactions with other glycoconjugates are also
      discussed and a vision for their future use in diagnosis and therapeutics is
      provided.

PMID- 17207927
TI  - Identification of a critical site in Wld(s): essential for Nmnat enzyme activity
      and axon-protective function.
AB  - The chimeric Wld(s) protein consisting of the N-terminal 70 amino acids of Ufd2
      and the complete sequence of nicotinamide mononucleotide adenylyltransferase1
      (Nmnat1), delays Wallerian degeneration in Wld(s) mice. Although Nmnat1 enzyme
      activity was showed to be critical for the function of Wld(s) protein, the
      expected phenotype was not observed in Nmnat1 transgenic mice. To further check
      whether Nmnat1 enzyme activity is involved, we aligned sequences of eukaryotic
      Nmnats, and found that Phe in helix A is highly conserved not only in various
      species, but also in different homologues. The Phe is a residue located near to
      the highly conserved GXFXPX(T/H)XXH motif and resides in the same helix as the
      last His of this conserved motif. To investigate the role of the conserved Phe in
      Nmnat activity, we made the point mutation of Phe. The Phe28 mutation of mouse
      Nmnat1 in Wld(s) completely abolished its Nmnat enzyme activity. To study the
      role of mutant Wld(s) in axon degeneration, herpes viruses were packaged to
      infect cultured SCGs. We found that the mutant Wld(s) failed to protect axon
      degeneration from morphological changes, microtubule integration and
      neurofilament degradation. Therefore, we have identified a Phe residue that
      critical for both enzyme activity of Nmnat and the axon-protective function of
      Wld(s), and further confirmed that Nmnat1 enzyme activity is required in Wld(s)
      function.

PMID- 17207928
TI  - Theophylline attenuates microwave-induced impairment of memory acquisition.
AB  - Numerous studies have shown that acute microwave exposure causes cognitive
      deficits in animals, possibly via hyperthermia, but the biological effect of
      microwave exposure on memory processing is still unknown. The release of
      adenosine is demonstrated to be a general way for the cells to respond to
      metabolically stressful conditions such as hypoxia and ischemia. The present
      study aimed to examine whether adenosine mediates biological effects of microwave
      exposure on memory processing using a continuous multiple-trial inhibitory
      avoidance task. Results demonstrated that microwave exposure for 20 min before
      training impaired memory acquisition and retention performance in mice, assessed
      by the number of training trials and by latency to enter the dark compartment.
      The mice exposed to microwave radiation showed a dose-dependent hyperthermia.
      Moreover, the cell numbers of hippocampus were decreased in the mice receiving
      microwave exposure at an average power density of 50 mW/cm(2), indicating the
      anatomical correlation to hippocampal-amygdaloid structures corresponding with
      the memory disrupt of the mice. Administration of theophylline, a nonspecific
      adenosine receptor antagonist, 30 min before microwave exposure, completely
      antagonized the impairment of inhibitory avoidance acquisition but not retention.
      These results suggest that the adenosine regulation pathway was partially
      involved in microwave-induced impairment of inhibitory avoidance memory.

PMID- 17207929
TI  - Identification of ER membrane targeting signal of kinectin.
AB  - Kinectin has been identified as a kinesin receptor on endoplasmic reticulum (ER).
      The ER membrane binding domain of kinectin is still obscure and is thought to
      require a half of the molecule. To determine the ER insertion site, we produced
      several constructs around N-terminus of kinectin connected with green fluorescent
      protein (GFP) and visualized the distribution in Cos-7 cells. The fragment of
      residues 7-29 appeared in the reticular pattern exactly colocalized with the ER
      marker but did not remain for a long time. On the other hand, residues 1-106
      maintained a reticular pattern for more than seven days. These results indicate
      that residues 7-29 of kinectin are sufficient for targeting to the ER membrane
      but insufficient for remaining on the ER.

PMID- 17207930
TI  - Ouabain-induced isoform-specific localization change of the Na+, K+-ATPase alpha
      subunit in the synaptic plasma membrane of rat brain.
AB  - Na+, K+-ATPase is one of major membrane proteins that has two subunits, alpha and
      beta. The alpha subunit has the ATPase activity and the ouabain binding site.
      Among four isoforms of the alpha subunit, expression of alpha1, alpha2, and
      alpha3, but not alpha4, is observed in matured rat brain. Ouabain is one of
      cardiac glycosides, and endogenous ouabain-like compounds have been recognized as
      a new class of steroid hormone. The alpha subunit is considered as their
      endogenous receptor. Recent studies envisaged the importance of membrane
      microdomains (MDs) as signaling platforms, which are recovered as a detergent
      resistant membrane microdomain fraction (DRM). Although this ATPase has been
      considered as a non-DRM protein, some amount of the alpha subunit was found to be
      a component of the DRM prepared from the synaptic plasma membrane fraction (SPM)
      of rat brain. Ouabain treatment increased the amount of alpha3 isoform, but not
      alpha1, in the DRM derived from synaptosome fraction and SPM. These results
      suggest that the localization of the alpha subunit of Na+, K+-ATPase is regulated
      with isoform-specific mechanisms and the physiological importance of DRM in the
      signal transduction of the endogenous ouabain-like steroid hormone in neurons.

PMID- 17207931
TI  - omega-Conotoxin MVIIA inhibits amygdaloid kindled seizures in Sprague-Dawley
      rats.
AB  - omega-Conotoxin MVIIA (omega-CTX MVIIA) is a reversible and potent antagonist of
      N-type voltage-dependent calcium channels (VDCCs) in neurons. In this study, we
      evaluated the effect of a fusion form of omega-CTX MVIIA with glutathione S
      transferase (GST) on amygdaloid kindled seizures. Intracerebraventricular
      (i.c.v.) injection of the fusion protein of GST-omega-CTX MVIIA significantly
      decreased seizure stage and shortened afterdischarge duration and generalized
      seizure duration in a dose-dependent and time-related manner. In addition, GST
      omega-CTX MVIIA significantly increased the GABA levels in the cortex and glycine
      levels in the brainstem. In contrast, GST alone did not have any effect on
      seizure behavior or neurochemical levels. These findings firstly demonstrate that
      the N-type VDCC is a potential therapeutic target for temporal lobe epilepsy. The
      mechanism of the anticonvulsant function of omega-CTX MVIIA is related to the
      blockade of N-type VDCC-mediated neurotransmitter release in the brain.

PMID- 17207932
TI  - Sustained division of spatial attention to multiple locations within one
      hemifield.
AB  - Attending to a location in space significantly improves stimulus perception at
      that location. Everyday experience requires the deployment of attention to
      multiple objects at different locations. Recent empirical evidence suggests that
      the "beam" of attention can be divided between non-contiguous areas of the visual
      field. Whether this is only possible when stimuli are presented in different
      hemifields and harder, if not impossible, when stimuli are in the same hemifield
      is an ongoing debate. Here we use an electrophysiological measure of sustained
      attentional resource allocation (the steady-state visual evoked potential, SSVEP)
      to address this question. In combination with behavioural data we demonstrate
      that splitting the attentional "beam" is in principle possible within one
      hemifield. However, results showed that task performance was in general lower for
      same-hemifield presentation as opposed to our previous study with different
      hemifield presentation [M.M. Muller, P. Malinowski, T. Gruber, S.A. Hillyard,
      Sustained division of the attentional spotlight, Nature 424 (2003) 309-312].
      SSVEP amplitude showed a mixed pattern of results for stimuli presented in the
      upper versus lower quadrant of the left visual hemifield under conditions of
      attending to two separated locations. Results are discussed in the light of the
      bilateral distribution advantage hypothesis and differences in stimulus salience
      between the upper and lower visual field.

PMID- 17207933
TI  - Abnormal frequency discrimination in children with SLI as indexed by mismatch
      negativity (MMN).
AB  - For several decades, the aetiology of specific language impairment (SLI) has been
      associated with a central auditory processing deficit disrupting the normal
      language development of affected children. One important aspect for language
      acquisition is the discrimination of different acoustic features, such as
      frequency information. Concerning SLI, studies to date that examined frequency
      discrimination abilities have been contradictory. We hypothesized that an
      auditory processing deficit in children with SLI depends on the frequency range
      and the difference between the tones used. Using a passive mismatch negativity
      (MMN)-design, 13 boys with SLI and 13 age- and IQ-matched controls (7-11 years)
      were tested with two sine tones of different frequency (700Hz versus 750Hz).
      Reversed hemispheric activity between groups indicated abnormal processing in
      SLI. In a second time window, MMN2 was absent for the children with SLI. It can
      therefore be assumed that a frequency discrimination deficit in children with SLI
      becomes particularly apparent for tones below 750Hz and for a frequency
      difference of 50Hz. This finding may have important implications for future
      research and integration of various research approaches.

PMID- 17207934
TI  - Prospects for aberration corrected electron precession.
AB  - Recent developments in aberration control in the TEM have yielded a tremendous
      enhancement of direct imaging capabilities for studying atomic structures.
      However, aberration correction also has substantial benefits for achieving ultra
      resolution in the TEM through reciprocal space techniques. Several tools are
      available that allow very accurate detection of the electron distribution in
      surfaces allowing precise atomic-scale characterization through statistical
      inversion techniques from diffraction data. The precession technique now appears
      to extend this capability to the bulk. This article covers some of the progress
      in this area and details requirements for a next-generation analytical
      diffraction instrument. An analysis of the contributions offered by aberration
      correction for precision electron precession is included.

PMID- 17207935
TI  - Temporal ontogeny of circuit activation prior to the onset of seizure
      susceptibility in EL/Suz mice.
AB  - The EL/Suz (EL) mouse is a model of multifactorial temporal lobe epilepsy in
      which seizures begin around 90 days of age, but can be hastened through increased
      exposure to human handling. In order to better understand seizure etiology in
      this mouse strain relative to seizure-resistant control mice, the present study
      examined region-specific neuronal activation in response to non-seizure-inducing
      handling implemented before the onset of seizure susceptibility. Immediate-early
      gene (cFos) expression emerged in EL mice by postnatal day (PND) 21 in the
      primary motor cortex, progressed to the locus ceruleus and prefrontal cortex by
      PND 35, and appeared in the hippocampus and amygdala by PND 70, as mice neared
      the age of onset for seizure susceptibility. Thus, mirroring the pattern observed
      during the course of a seizure, specific brain regions were differentially
      recruited to a neural network for seizure predisposition before the onset of
      seizure susceptibility. This developmental pattern of early and transient neural
      activation represents an important window for the study of causal mechanisms of
      seizure susceptibility following exposure to environmental triggers.

PMID- 17207937
TI  - Four hypotheses on mitochondria's role in the development and regulation of
      oxidative stress in the normal state, cell pathology and reversion of tumor
      cells.
AB  - The biological evolution has resulted in adaptation of both unicellular and
      multicellular organisms to negative effect of excessive O2 in reply to gradual
      increase of free oxygen (O2) contents in the earth atmosphere. This adaptation
      has led to formation of various antioxidant systems in the organism. Such system
      within the cell has hierarchic structure and is represented by at least than
      three levels of protection: antioxygene, antiradical and antiperoxide. The first
      and most effective antioxidant level is represented as mitochondrial respiration
      able to perform several functions. One of these functions is antioxygene since
      the very the mitochondria's capability to be a main O2 consumer in the cell
      provides for low but sufficient for respiration and energy supply levels of O2
      partial pressure and dependent concentrations of active O2 forms. The latters,
      being signal molecules at certain values, modify regular and synthetic processes
      in the cells either directly or indirectly. This is the possibility for
      mitochondria to more extensively affect the intracellular processes than simply
      produce ATP. In case of defective of the cell first protection line the hyperoxia
      starts due to poor utilization of the incoming O2. Change in mitochondria's
      "capacity" (quantity, size and maturity level of mitochondria) anyway occurring
      in the cells are an efficient way of regulation of the oxy-peroxide condition
      (oxidative stress) and related signal channels. The relationship between changes
      in the condition of cells, i.e. from their normal state to different pathologic
      forms, and growing disbalance Delta(PO-AO) between its pro-oxygen (PO) and anti
      oxygen (AO) components has been assumed. It is expected that during the evolution
      the cell could have supposedly acquired a sequence of "specialized" Delta(PO-AO)
      disbalances. Each sequence needs to implement a certain set of biochemical
      processes. The probability of Delta(PO-AO) disbalance gradation with
      specification of their value ranges has been determined. These ranges identify or
      impact certain cell state, namely proliferation of normal cell (oxidative
      mitogenesis), ageing, A1 apoptosis, carcinogenesis, A2 apoptosis, and oxidative
      cytolysis. The cited assumption allows us to: (1) explain reverse dependence of
      cell proliferation due to the level of their differentiation, increase in the
      amount and activity of mitochondria as an indispensable condition for the
      disbalance shift towards differentiation, (2) bring up the idea that regress of
      the cells, and in particular tumour cells, directly results from the Delta(PO-AO)
      disbalance decrease to certain levels under the influence of reverse inductors,
      (3) explain relatively easy and frequent embryonic and stem cells malignancy, and
      also their reversal normalization. These phenomena occur due to small number
      and/or size of mitochondria in the designated cells. To verify the above
      mentioned hypotheses it is primarily necessary to be able to stimulate and slow
      down the mitochondria biogenesis in the embryonic, stem, ageing, cancer and other
      cells.

PMID- 17207938
TI  - Prizes to solve problems in and beyond medicine, big and small: it can work.
AB  - This article complements Dr. Charlton's follow-up of David Horrobin's suggestion
      in Nature two decades ago to offer sizeable prizes for practical approaches to
      either eliminate a problem in medicine or reduce the cost of its solution.
      Examples from the 20th and 21st centuries illustrate that prizes--small and big-
      have generated sustained and successful attacks on defined problems in biology,
      physics and, lately, mathematics. Provided that glittering prizes are offered and
      awarded with care, they can lead to effective problem-solving in medicine and
      related biomedical sciences as well.

PMID- 17207936
TI  - DNA damage responses in neural cells: Focus on the telomere.
AB  - Postmitotic neurons must survive for the entire life of the organism and be able
      to respond adaptively to adverse conditions of oxidative and genotoxic stress.
      Unrepaired DNA damage can trigger apoptosis of neurons which is typically
      mediated by the ataxia telangiectasia mutated (ATM)-p53 pathway. As in all
      mammalian cells, telomeres in neurons consist of TTAGGG DNA repeats and several
      associated proteins that form a nucleoprotein complex that prevents chromosome
      ends from being recognized as double strand breaks. Proteins that stabilize
      telomeres include TRF1 and TRF2, and proteins known to play important roles in
      DNA damage responses and DNA repair including ATM, Werner and the catalytic
      subunit of DNA-dependent protein kinase (DNA-PKcs). We have been performing
      studies of developing and adult neurons aimed at understanding the effects of
      global and telomere-directed DNA damage responses in neuronal plasticity and
      survival in the contexts of aging and neurodegenerative disorders. Deficits in
      specific DNA repair proteins, including DNA-PKcs and uracil DNA glycosylase
      (UDG), render neurons vulnerable to adverse conditions of relevance to the
      pathogenesis of neurodegenerative disorders such as Alzheimer's disease and
      stroke. Similarly, early postmitotic neurons with reduced telomerase activity
      exhibit accentuated responses to DNA damage and are prone to apoptosis
      demonstrating a pivotal role for telomere maintenance in both mitotic cells and
      postmitotic neurons. Our recent findings suggest key roles for TRF2 in regulating
      the differentiation and survival of neurons. TRF2 affects cell survival and
      differentiation by modulating DNA damage pathways, and gene expression. A better
      understanding of the molecular mechanisms by which neurons respond to global and
      telomere-specific DNA damage may reveal novel strategies for prevention and
      treatment of neurodegenerative disorders. Indeed, work in this and other
      laboratories has shown that dietary folic acid can protect neurons against
      Alzheimer's disease by keeping homocysteine levels low and thereby minimizing the
      misincorporation of uracil into DNA in neurons.

PMID- 17207939
TI  - Use of gabapentin during pregnancy to reduce brain damage in new-born infants
      that are premature or at risk of perinatal asphyxia.

PMID- 17207940
TI  - Alkaloids from Sarcomelicope megistophylla.
AB  - Two new alkaloids were isolated from the bark of Sarcomelicope megistophylla.
      Cyclomegistine B (1), a new quinolone alkaloid, that possesses a rare
      cyclobuta[b]quinoline ring system and sarcomejine B (2) which is a quinolone
      alkaloid with an unusual side chain. The structure of both compounds was
      elucidated on the basis of MS data and extensive NMR studies.

PMID- 17207941
TI  - Responses of a sub-oscine bird during playback: effects of different song
      variants and breeding period.
AB  - Vermilion flycatchers (Pyrocephalus rubinus) vary their song rate and song length
      across the breeding season. Males sing more and longer songs after nest
      construction than before. Here we explored the possibility that this variation is
      meaningful to territorial males. Using a playback approach, we tested several
      males with different variations in song output (i.e. variations in song length
      and song rate) in different periods of the breeding season (i.e. before and after
      the onset of nest construction). We found that males call more in response to
      playbacks of long and short songs before the onset of nest construction. However,
      after nest construction began they responded flying more when exposed to long
      songs than to short songs. These results show that vermilion flycatcher
      discriminates between different variants of song length, and suggest that males
      react to long songs as if they were more threatening signals than short songs,
      especially after the onset of nest construction. We did not find evidence of
      males discriminating between a high and a low song rate. We discuss some possible
      implications for song function in this sub-oscine species, and compare these
      findings with other results in oscine species.

PMID- 17207942
TI  - Rat testicular germ cell type(s) targeted by anti-spermatogenic agents in vivo
      and their recovery on withdrawal of treatment--a flow cytometric study.
AB  - Spermatogenesis goes through very critically and precisely balanced ratios of
      germ cells with diverse DNA ploidies (1C, 2C and 4C). Antispermatogenic agents
      that reversibly interrupt spermatogenesis may have a contraceptive relevance.
      With a view to study the precise mechanism of action of antispermatogenic agents
      and identify the germ cell type(s) targeted by various agents in vivo,
      spermatogenic cells with diverse DNA ploidies were measured in rat testis during
      treatment and recovery with compounds CDRI-84/35, gossypol and estradiol, using
      Flow Cytometry. Rats were treated with either CDRI-84/35 (100mg/(kg day) for 15
      days followed by 25mg/(kg day) for 55 days) or gossypol (20mg/(kg day) for 70
      days) or estradiol benzoate (2.5microg/(rat day) for 70 days) and 3 rats from
      each group were sacrificed after 22, 41, 53 and 70 days of treatment to monitor
      the changes in population of 1C, 2C, S-phase and 4C germ cell types. Treatment
      with CDRI-84/35 resulted in a significant and rapid drop in 1C population with a
      concomitant and parallel rise in 2C population. In gossypol-treated animals 1C
      peak disappeared gradually and the arrest was seen predominantly at 2C stage and
      partially at 4C stage. At the end of the treatment most of the germ cells were
      arrested at 2C stage. Estradiol affected spermatogenesis differently with 1C
      population falling in complement to rise in both 2C and 4C peaks. Germ cells were
      mainly arrested at the 4C stage after the treatment. The data suggest that germ
      cells fail to enter meiosis in CDRI-84/35-treated rats. Few cells entering
      meiosis do not complete the cell division and remain arrested at 4C stage.
      However in case of estradiol and gossypol the meiotic 4C cells become incapable
      of further differentiation into haploid cells. After receiving 70 days of
      treatment a few rats were allowed to recover for 60, 90 and 120 days. The
      population of various germ cell types in the testis of recovery-group animals
      indicated that spermatogenesis resumes substantially in case of estradiol
      treatment and partially in case of treatment with the other two agents.

PMID- 17207943
TI  - Matrices containing NaCMC and HPMC 1. Dissolution performance characterization.
AB  - In this study hydroxypropylmethylcellulose (HPMC) and sodium
      carboxymethylcellulose (NaCMC) were used as polymeric carriers to improve
      controlled release performances of matrix tablets containing a soluble drug. The
      drug release behaviour of the systems containing these two polymers mixture and
      each material separately was investigated. To evaluate the effect of the
      dissolution medium pH, on the drug release performance, release tests were
      conducted at pH 1, 4.5 and 6.8. In vitro release studies demonstrated that the
      mixture of the two cellulose derivatives enables a better control of the drug
      release profiles at pH 4.5 and at 6.8 both in term of rate and mechanism. Texture
      analysis on the swollen tablets helps to understand drug release kinetic and
      mechanism. In fact, the results obtained confirm that a gel, which is
      characterized by high strength and consistence is less susceptible to erosion and
      chains disentanglement and the drug release mechanism is mainly governed by
      diffusion. On the contrary, gels, which show a low strength and texture, have low
      resistance to the fluid erosion action and the release of the active molecule is
      manly due to polymer relaxation and chains disentanglement moving the drug
      delivery kinetic towards an erosion/relaxation mechanism.

PMID- 17207944
TI  - Haloperidol-loaded PLGA nanoparticles: systematic study of particle size and drug
      content.
AB  - We have produced haloperidol-loaded PLGA/PLA nanoparticles by using two
      emulsification-solvent evaporation methods: homogenization and sonication. We
      have established how five independent processing parameters and two materials
      characteristics control the particle size and drug content. The interdependencies
      between processing and materials parameters and the subsequent nanoparticle
      characteristics are discussed in terms of underlying scientific principles that
      are broadly applicable to the production of drug-loaded polymer nanoparticles.
      This level of understanding should quicken the pace of designing protocols for
      making new drug-PLGA nanoparticles. It was determined that the particle size of
      haloperidol-loaded PLGA/PLA nanoparticles is effectively controlled by the amount
      of shear stress transferred from the energy source to the organic phase, which is
      strongly correlated to the following parameters: type of applied energy, aqueous
      phase volume, and polymer concentration in the organic solvent. The drug content
      of these nanoparticles is controlled by reducing the diffusion of the drug from
      the organic to the aqueous phase during the solvent evaporation stage of the
      preparation and by increasing the drug-polymer interactions. The following
      significantly inhibit drug diffusion: large particle size, higher polymer
      concentration and polymer molecular weight, and reducing the drug solubility in
      the aqueous phase by adjusting the pH. Specific drug-polymer interactions are
      engineered by optimizing the lactide to glycolide ratio (L:G ratio) and including
      specific polymer end groups. When optimized, the drug-loaded PLGA/PLA
      nanoparticles contain as much as 2.5% haloperidol.

PMID- 17207945
TI  - Structural and thermal characterization of glyceryl behenate by X-ray diffraction
      coupled to differential calorimetry and infrared spectroscopy.
AB  - Physical and thermal properties of glyceryl behenate (Compritol 888 ATO) used as
      sustained-release matrix in pharmaceutical applications are studied by coupled
      time-resolved synchrotron X-ray diffraction and Differential Scanning Calorimetry
      combined with Infrared Spectroscopy. With these techniques, all polymorphs formed
      in glyceryl behenate, analyzed as received and after various thermal treatments
      from quenching to slow crystallization, are characterized. By using different
      well-controlled mixtures of mono-, di- and tribehenate, we identify each lamellar
      phase observed in the glyceryl behenate. Finally the influence of the
      crystallization rate on the formation of preferential conformations was also
      analyzed in order to bring insights into the polymorphism of glyceryl behenate.
      By changing the crystallization rate of the sample, it was shown that one can
      favor the formation of preferential polymorphs in the sample. In particular the
      crystallization at 10 degrees C/min seems to be well adapted for producing a
      single lamellar phase with a period of 60.9 A while a crystallization rate of 0.4
      degrees C/min produces three different lamellar phases.

PMID- 17207946
TI  - Intestinal absorption of novel-dipeptide prodrugs of saquinavir in rats.
AB  - Saquinavir (SQV) was the first human immuno-virus-1 (HIV-1) protease inhibitor
      approved by FDA. However, P-glycoprotein (P-gp), an efflux pump limits its oral
      and brain bioavailabilities. The objective of this study is to investigate
      whether prodrug modification of SQV to dipeptide prodrugs Valine-Valine
      Saquinavir (Val-Val-SQV) and Glycine-Valine-Saquinavir (Gly-Val-SQV) targeting
      intestinal peptide transporter can enhance intestinal permeability of SQV by
      circumventing P-gp mediated efflux. Single pass intestinal perfusion experiments
      in rat jejunum were performed to calculate the absorption rate constant and
      intestinal permeability of SQV, Val-Val-SQV and Gly-Val-SQV. Equimolar
      concentration (25 microM) of SQV, Val-Val-SQV and Gly-Val-SQV were employed in
      the perfusion studies. Perfusion experiments were also carried out in the
      presence of cyclosporine (10 microM) and glycyl-sarcosine (20 mM). Absorption
      rate constants in rat jejunum (ka) for SQV, Val-Val-SQV and Gly-Val-SQV were
      found to be 14.1+/-3.4x10(-3), 65.8+/-4.3x10(-3), and 25.6+/-5.7x10(-3) min(-1),
      respectively. Enhanced absorption of Val-Val-SQV and Gly-Val-SQV relative to SQV
      can be attributed to their translocation by the peptide transporter in the
      jejunum. Significant permeability enhancement of SQV across rat jejunum was
      observed in the presence of cyclosporine 10 microM (P-gp inhibitor). However,
      permeability of Val-Val-SQV was unchanged in the presence of cyclosporine
      suggesting lack of any interaction of the prodrug with efflux pump. Intestinal
      absorption of Val-Val-SQV was significantly inhibited in the presence of gly-sar
      indicating the involvement of peptide transporter in intestinal absorption. In
      conclusion, peptide transporter targeted prodrug modification of P-gp substrates
      could lead to shielding of these drug molecules from efflux pumps.

PMID- 17207947
TI  - In vitro behavior of a phosphate ester prodrug of amprenavir in human intestinal
      fluids and in the Caco-2 system: illustration of intraluminal supersaturation.
AB  - As a result of their improved aqueous solubility, the development of phosphate
      ester prodrugs is an interesting approach to increase intestinal absorption of
      poorly water-soluble drugs. Absorption of a drug from its phosphate ester prodrug
      is based on intestinal dephosphorylation of the prodrug which may result in
      intraluminal supersaturation of the parent drug, followed by an increased
      absorptive flux across the intestinal mucosa. In this study, we evaluated the
      behavior of fosamprenavir, a phosphate ester prodrug of amprenavir, in the Caco-2
      system and in aspirated human intestinal fluids (HIF), both showing phosphatase
      activity. Starting from a solution of fosamprenavir in HIF, a supersaturated
      solution of amprenavir was generated and maintained during a time period
      sufficient for absorption. Moreover, supersaturation of amprenavir resulted in an
      enhanced flux across Caco-2 monolayers. To our knowledge, this is the first
      illustration of supersaturation in real intestinal media. Next, we showed an
      inhibitory effect of inorganic phosphate on the dephosphorylation of
      fosamprenavir, both in the Caco-2 model and in HIF. As a consequence, phosphate
      buffered media, including fasted state simulated intestinal fluid (FaSSIF), are
      incompatible with the study of phosphate ester prodrugs and should be replaced
      with media containing a biorelevant phosphate concentration (0.4-1 mM) and
      another buffering compound such as 2-morpholinoethanesulfonic acid (MES).

PMID- 17207948
TI  - Experimental study of wet granulation in fluidized bed: impact of the binder
      properties on the granule morphology.
AB  - In this work, the effect of the physicochemical properties of aqueous
      hydroxypropyl-cellulose (HPC) binder solutions and different pharmaceutical
      excipients (mannitol and anhydrous CaHPO(4)) on the agglomeration kinetics and
      granule properties were investigated. First, a particle size distribution (PSD)
      analysis together with a detailed analysis of morphological properties of the
      excipient particles were performed. Second, the viscosity, density, surface
      tension and size of the spray droplets of binder solutions with different HPC
      concentrations were determined and wetting characteristics of the binders on the
      excipients were measured. Third, several fluid bed wet granulation experiments
      were conducted for pure excipients and their blends with binder solution of
      different HPC concentrations in a pilot plant Wurster granulator. The observed
      granule growth for different binder concentrations was a strong function of the
      binder concentration and the excipient solubility. For mannitol, a significant
      "coating" period followed by a slow granule growth was observed for the case with
      the diluted 5% binder. The "coating" period was significantly shorter for the 10%
      HPC binder and did not exist for the 15% HPC for which immediate and fast granule
      growth was observed. For anhydrous CaHPO(4) (trademark A-TAB), no growth was
      observed for the 10% HPC binder and a long coating period followed by fast
      granule growth was observed for the 15% HPC. Simple physically based criteria
      were also evaluated, which employ the morphological properties of excipients
      (size and surface roughness) together with physical properties of the used binder
      for prediction of the coating versus agglomeration regime at given flow
      conditions (collision velocity). As expected, a preferential coalescence and
      growth of the mannitol granules from the blend of mannitol+A-TAB was observed.
      Finally, the mechanical and morphological properties of the produced granules
      were measured and correlated to the HPC concentration of the binder used in the
      experiments. A clear correlation between the granule porosity (evaluated by X-ray
      tomography) and the binder concentration was found for the mannitol granules.

PMID- 17207949
TI  - The perception of FM sweeps by Chinese and English listeners.
AB  - Frequency-modulated (FM) signals are an integral acoustic component of
      ecologically natural sounds and are analyzed effectively in the auditory systems
      of humans and animals. Linearly frequency-modulated tone sweeps were used here to
      evaluate two questions. First, how rapid a sweep can listeners accurately
      perceive? Second, is there an effect of native language insofar as the language
      (phonology) is differentially associated with processing of FM signals? Speakers
      of English and Mandarin Chinese were tested to evaluate whether being a speaker
      of a tone language altered the perceptual identification of non-speech tone
      sweeps. In two psychophysical studies, we demonstrate that Chinese subjects
      perform better than English subjects in FM direction identification, but not in
      an FM discrimination task, in which English and Chinese speakers show similar
      detection thresholds of approximately 20 ms duration. We suggest that the better
      FM direction identification in Chinese subjects is related to their experience
      with FM direction analysis in the tone-language environment, even though supra
      segmental tonal variation occurs over a longer time scale. Furthermore, the
      observed common discrimination temporal threshold across two language groups
      supports the conjecture that processing auditory signals at durations of
      approximately 20 ms constitutes a fundamental auditory perceptual threshold.

PMID- 17207950
TI  - Ethnotherapeautic management of skin diseases among the Kikuyus of Central Kenya.
AB  - Skin health is increasingly becoming an important aspect of primary health care
      among many communities particularly because of the increased challenge of HIV
      AIDS, skin conditions being among the common opportunistic diseases in immuno
      compromised individuals. This study investigated the use of traditional remedies
      in managing various skin conditions in the Central Province of Kenya. Fifty-seven
      plant species in 31 families were identified as regularly utilized. Of these
      plants 27 species had a frequency of three and above. Some of the highly utilized
      plant species include: Croton megalocarpus Hutch., Senna didymobotrya (Fresen.)
      Irwin & Barneby, Vernonia lasiopus O. Hoffm., Croton macrostachyus Del. and Aloe
      secundifolia Engl. In the majority of the cases the sap or occasionally the latex
      was applied directly on the affected areas. In other cases the plant parts were
      heated and used as poultice. Only in few conditions were the plant parts boiled
      and the extract used for washing affected areas, probably acting as antiseptic.
      This study found that 14 skin conditions were commonly managed using herbal
      preparations. Of these conditions nine (9) had informant consensus of 0.5 and
      above, with the highest consensus found in management of swellings and skin
      sores. Soils were also cited as an important non-plant resource for management of
      skin conditions especially those associated with measles. Since most skin
      conditions are caused by microorganisms such as bacteria, viruses and fungi, the
      medicinal plants and other resources reported in this study form a justifiable
      basis for antimicrobial trials, pharmacological and phytochemical analysis, with
      promising results.

PMID- 17207951
TI  - Fingerprinting quality control of Qianghuo by high-performance liquid
      chromatography-photodiode array detection.
AB  - A novel, simple and accurate fingerprint method was developed using high
      performance liquid chromatography-photodiode array detection (HPLC-DAD) for the
      quality control of Qianghuo, a Tibetan folk and Chinese herbal medicine used as a
      diaphoretic, an antifebrile and an anodyne. For the first time, the feasibility
      and advantages of employing chromatographic fingerprint were investigated and
      demonstrated for the evaluation of Qianghuo by systematically comparing
      chromatograms of aqueous extracts with the professional analytical software
      recommended by State Food and Drug Administration (SFDA). Our results revealed
      that the chromatographic fingerprint combing similarity evaluation could
      efficiently identify and distinguish raw herbs of Qianghuo from different sources
      and different species. The effects on Notopterygium forbesii Boiss (Apiaceae)
      chromatographic fingerprints resulted from collecting locations, harvesting time
      were also examined.

PMID- 17207952
TI  - Analysis of propolis from Baccharis dracunculifolia DC. (Compositae) and its
      effects on mouse fibroblasts.
AB  - This paper confirms Baccharis dracunculifolia DC. (Compositae) as the main
      botanical source of the propolis from southeastern Brazil (state of Sao Paulo)
      investigated to ascertain specific biological activity in relation to mouse NIH
      3T3 fibroblasts, skin cells directly involved in the cicatrization processes.
      Flavonoid and total phenolic compounds were determined by spectrophotometry, and
      chemical composition by HPLC; the chromatographic profile, characterized largely
      by flavonoids and aromatic acids, was found to be qualitatively similar to that
      of Baccharis dracunculifolia DC. The adsorption of phenolic compounds in the
      propolis to skin powder was also investigated, and 68% of these compounds
      adsorbed to the skin powder. At concentrations from 0.12 to 7.81 microg/ml, the
      propolis revealed no statistical significant differences from its control
      solutions; however, at concentrations of 31.25 microg/ml or more, the propolis
      was toxic to NIH-3T3 cells. Thus, the propolis from Baccharis dracunculifolia DC.
      (Compositae) presents an in vitro concentration-dependent toxicity on mouse NIH
      3T3 fibroblasts.

PMID- 17207953
TI  - Tateyamaria omphalii gen. nov., sp. nov., an alpha-Proteobacterium isolated from
      a top shell Omphalius pfeifferi pfeifferi.
AB  - A Gram-negative, strictly aerobic, coccoid to short rod-shaped marine bacterium
      strain MKT107(T) was isolated from the molluscan top shell Omphalius pfeifferi
      pfeifferi collected on the coast of Japan. Phylogenetic analysis based on the 16S
      rRNA gene sequence showed that strain MKT107(T) constitutes a new lineage in
      alpha-Proteobacteria related to the genera Nereida, Roseobacter, Staleya,
      Oceanibulbus and Sulfitobacter. Strain MKT107(T) was found to require salt for
      its growth and to be mesophilic. It contained 18:1omega7c and 16:0 as major
      cellular fatty acids and 3-OH 10:0 and 3-OH 12:0 as hydroxy fatty acids. The DNA
      base composition of the isolate was 61.6 mol% G+C. The major quinone was Q-10.
      Sufficient differences existed to distinguish this strain from currently
      recognized bacterial genera. Therefore, the isolate is classified as representing
      a new genus and species, Tateyamaria omphalii gen. nov., sp. nov. (type strain
      MKT107(T) =IAM 15108(T) =KCTC 12333(T); GenBank accession no. AB193438).

PMID- 17207954
TI  - Morphine and its metabolites: analytical methodologies for its determination.
AB  - The present article reviews the methods of determination published for morphine
      and its metabolites covering the period from 1980 until at the first part of
      2006. The overview includes the most relevant analytical determinations
      classified in the following two types: (1) non-chromatographic methods and (2)
      chromatographic methods.

PMID- 17207955
TI  - Effects of ghrelin and its analogues on chicken ovarian granulosa cells.
AB  - The aim of these in vitro experiments was (1) to examine the effects of ghrelin
      on the basic functions of ovarian cells (proliferation, apoptosis, secretory
      activity); (2) to determine the possible involvement of the GHS-R1a receptor and
      PKA- and MAPK-dependent post-receptor intracellular signalling cascades; (3) to
      identify the active part of the 28-amino acid molecule responsible for the
      effects of ghrelin on ovarian cells. We compared the effect of full-length
      ghrelin 1-28, a synthetic activator of GHS-R1a, GHRP6, and ghrelin molecular
      fragments 1-18 and 1-5 on cultured chicken ovarian cells. Indices of cell
      apoptosis (expression of the apoptotic peptide bax and the anti-apoptotic peptide
      bcl-2), proliferation (expression of proliferation-associated peptide PCNA), and
      expression of protein kinases (PKA and MAPK) within ovarian granulosa cells were
      analysed by immunocytochemistry. The secretion of progesterone (P(4)),
      testosterone (T), estradiol (E(2)) and arginine-vasotocin (AVT) by isolated
      ovarian follicular fragments was evaluated by RIA/EIA. It was observed that
      accumulation of bax was increased by ghrelin 1-28, GHRP6 and ghrelin 1-18, but
      not by ghrelin 1-5. Expression of bcl-2 was suppressed by addition of ghrelin 1
      28, GHRP6 and ghrelin 1-5, but promoted by ghrelin 1-18. The occurrence of PCNA
      was reduced by ghrelin 1-28, GHRP6, ghrelin 1-18 and ghrelin 1-5. An increase in
      the expression of MAPK/ERK1, 2 was observed after addition of ghrelin 1-28, GHRP6
      and ghrelin 1-18, but not ghrelin 1-5. The accumulation of PKA decreased after
      treatment with ghrelin 1-28 and increased after treatment with GHRP6 and ghrelin
      1-18 but not ghrelin 1-5. Secretion of P(4) by ovarian follicular fragments was
      decreased after addition of ghrelin 1-28 or ghrelin 1-5 but stimulated by GHRP6
      and ghrelin 1-18. Testosterone secretion was inhibited by ghrelins 1-28 and 1-18,
      but not by GHRP6 or ghrelin 1-5. Estradiol secretion was reduced after treatment
      with ghrelin 1-28 but stimulated by ghrelins 1-18 and 1-5; GHRP6 had no effect.
      AVT secretion was stimulated by ghrelin 1-28, GHRP6 and ghrelin 1-18, but
      inhibited by ghrelin 1-5. The comparison of the effects of the four ghrelin
      analogues on nine parameters of ovarian cells suggest (1) a direct effect of
      ghrelin on basic ovarian functions-apoptosis, proliferation, steroid and peptide
      hormone secretion; (2) that the majority of these effects can be mediated through
      GHS-R1a receptors; (3) an effect of ghrelin on MAPK- and PKA-dependent
      intracellular mechanisms, which can potentially mediate the action of ghrelin at
      the post-receptor level; (4) that ghrelin residues 5-18 may be responsible for
      the major effects of ghrelin on the avian ovary.

PMID- 17207956
TI  - PET CT imaging in patients undergoing sentinel node biopsy for melanoma.
AB  - AIMS: Sentinel lymph node biopsy (SLNB) has been adopted in the surgical
      treatment of melanoma to reduce morbidity and enhance staging. Positron emission
      tomography with computerised tomography (PET/CT) has been utilised in the staging
      of patients with malignancy though the role of this imaging modality in early
      stage melanoma is unclear. This study examined the preoperative value of PET/CT
      in patients undergoing SLNB for malignant melanoma. METHODS: Patients presenting
      with primary melanoma without evidence of either locoregional or systemic
      metastasis were considered candidates for SLNB. Selected patients underwent
      preoperative PET/CT followed by definitive surgical therapy including SLNB with
      regional lymphadenectomy, where indicated. RESULTS: During a 12-month period 83
      patients were identified as having undergone SLNB for melanoma, of which 37 (45%)
      had preoperative PET/CT. Mean melanoma thickness 1.9 mm and 2.4 mm (PET/CT vs. no
      PET/CT, p>0.05). 13 (15.6%) patients were found to have lymphatic metastasis at
      SLNB; nine of these patients underwent PET/CT, only two of these scans were
      suggestive of lymphatic metastasis (positive predictive value 24%, negative
      predictive value 76%). PET/CT revealed no unheralded metastatic disease but did
      identify a second occult malignancy in 4 (10.8%) patients undergoing therapy for
      melanoma. CONCLUSIONS: The results of this study do not support the use of PET/CT
      in patients undergoing SLNB for melanoma. SLNB appears to be a more sensitive
      staging modality in the detection of lymphatic metastasis; however PET/CT may
      have a future role as a screening tool for malignancy.

PMID- 17207957
TI  - Liver resections for hepatocellular carcinoma in chronic liver disease:
      experience in an Italian centre.
AB  - AIM: Liver resection (LR) and transplantation are the best options for treatment
      of hepatocellular carcinoma (HCC). We retrospectively analysed the experience
      obtained with LR for HCC in chronic liver disease patients. METHODS: Up until May
      2005, 248 patients with HCC were evaluated, and 113 resected. Of these, 97 with
      chronic liver disease, who underwent a total of 100 resections, form the basis of
      this study. Age of the patients was 65.6+/-9.2 years (range 32-81, male/female
      76/21). In 77 cases there was unifocal and in 23 multinodular tumour; in 61 the
      size of the tumours was < or =5 cm and in 39>5 cm. Limited resections were
      performed in 15 cases, resections of 1-2 segments in 51, and major hepatectomies
      in 34. RESULTS: Blood transfusions were required in 28 cases. Three patients died
      postoperatively, from liver failure and/or sepsis. Seventeen patients had
      nonlethal complications (mostly liver dysfunction, often with signs of amplified
      inflammatory response, including ARDS, without evident sources of sepsis). The 5-
      and 10-year survival rates were 44% and 24%, respectively. Decreased survival was
      significantly related to increasing number of tumour nodules and degree of liver
      fibrosis/presence of cirrhosis, and with the expression of markers of
      carcinogenesis in a sub-group who received this assessment. At 5 years the rate
      of liver HCC recurrence was 46%, however, death was unrelated to recurrence in
      41% of non-survivors. CONCLUSIONS: Surgery for HCC achieves acceptable early and
      long-term results. However, the patterns affecting perioperative outcome must be
      better understood, and the high recurrence rate warrants further trials to assess
      preventive treatments after LR.

PMID- 17207958
TI  - Malignant disease in peptic ulcer surgery patients after long term follow-up: a
      cohort study of 1992 patients.
AB  - AIMS: To assess the effect of previous peptic ulcer surgery on subsequent
      malignant events, in particular in relation to previous vagotomy, a historical
      cohort study was conducted. METHODS: All patients undergoing surgery for peptic
      ulcer disease with accurate follow-up data at a large peptic ulcer clinic in the
      Western Infirmary, Glasgow, from 1965 to 1983 were assessed. All cancer events
      and specific cancer events (gastric, bronchial, laryngeal, colorectal, bladder,
      breast, prostate, pancreas, kidney, oesophageal cancers) were determined as
      outcome measures and expressed as standardised incidence ratio (SIR). RESULTS:
      Vagotomy and drainage accounted for 67% of all procedures for peptic ulcer
      disease. Eighty-three percent were habitual smokers. For all peptic ulcer surgery
      patients, the SIR for all cancer events was 0.86. For specific cancers, the SIRs
      were bronchial cancer (SIR 1.13); laryngeal cancer (SIR 2.17), colorectal cancer
      (SIR 0.67). For vagotomised patients the risk of gastric cancer was significantly
      elevated (SIR 1.50). CONCLUSIONS: An excess of cancers attributable to smoking
      have been found in peptic ulcer surgery patients. Vagotomised patients have a
      higher risk of gastric cancer after long term follow-up. This finding may have
      implications for screening and the safety of long term acid suppression with
      agents such as proton pump inhibitors.

PMID- 17207960
TI  - Intraductal papillary mucinous neoplasms of the pancreas.
AB  - BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are neoplasms
      of the pancreatic duct epithelium characterized by intraductal papillary growth
      and thick mucin secretion. Quantities of mucin fill the main and/or branches of
      pancreatic ducts and cause ductal dilatation. This review encompasses IPMNs,
      including symptoms, diagnosis, management, and prognosis. METHODS: A Pubmed
      database search was performed. All abstracts were reviewed and all articles in
      which cases of IPMNs could be identified were further scrutinized. Further
      references were extracted by cross-referencing. RESULTS: Only one-third of all
      patients are symptomatic. According to the site of involvement, IPMNs are
      classified into three types: main duct type, branch duct type, and combined type.
      Most branch type IPMNs are benign, while the other two types are frequently
      malignant. The presence of large mural nodules increases the possibility of
      malignancy in all types. Presence of a large branch type IPMN and marked
      dilatation of the main duct indicate the existence of adenoma at least.
      Synchronous or metachronous malignancies may be developed in various organs.
      Endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography, and
      intraductal ultrasonography clearly demonstrate ductal dilatation and mural
      nodules, while magnetic resonance pancreatography best visualizes the entire
      outline of IPMNs. CONCLUSIONS: Prognosis is excellent after complete resection of
      benign and non-invasive malignant IPMNs. The extent of pancreatic resection and
      the intraoperative management of resection margins remain controversial. Total
      pancreatectomy should be reserved for patients with resectable but extensive
      IPMNs involving the whole pancreas; its benefits, however, must be balanced
      against operative and postoperative risks. Regular monitoring for disease
      recurrence is important after surgery.

PMID- 17207959
TI  - Adjuvant chemotherapy with 5-fluorouracil, doxorubicin and mitomycin-C (FAM) for
      6 months after curative resection of gastric carcinoma.
AB  - AIM: This study aimed to evaluate the efficacy and safety of 5-fluorouracil (5
      FU), doxorubicin and mitomycin-C (FAM) adjuvant chemotherapy in patients who had
      undergone curative resection of gastric carcinoma. METHODS: From Nov 1999 to Jan
      2002, 291 consecutive patients with stage IB-IIIB gastric adenocarcinoma were
      given FAM adjuvant chemotherapy. Chemotherapy comprised intravenous 5-FU 600
      mg/m(2) (days 1, 8, 29 and 36), doxorubicin 30 mg/m(2) (days 1 and 29) and
      mitomycin-C 10 mg/m(2) (day 1), every 8 weeks for 6 months. RESULTS: The median
      follow-up time was 60.6 months, 92 patients died, and 93 patients had recurrent
      disease. The 5-year overall survival (OS) rates were 85.9% for stage IB, 72.1%
      for stage II, 58.0% for stage IIIA, and 48.2% for stage IIIB (p=0.002). The 5
      year relapse-free survival (RFS) rates were 85.2% for stage IB, 71.2% for stage
      II, 53.3% for stage IIIA, and 39.2% for stage IIIB (p<0.001). A total of 769
      cycles of chemotherapy were delivered, and 15 patients experienced grade 3 or
      higher leukopenia. The most common grade 3 or higher non-hematologic toxicity was
      nausea/vomiting (11 patients), followed by stomatitis (3 patients). CONCLUSIONS:
      Adjuvant chemotherapy with FAM for 6 months for gastric carcinoma indicated
      comparable RFS and OS with an acceptable toxicity profile.

PMID- 17207961
TI  - Hepatic veno-occlusive disease after neoadjuvant treatment of colorectal liver
      metastases with oxaliplatin: a lesson of the month.
AB  - A patient is presented who was treated with neoadjuvant oxaliplatin-based
      chemotherapy followed by hepatic resection complicated by fatal liver failure.
      Histopathological examination revealed hepatic veno-occlusive disease, which is
      an infrequent reported side effect of oxaliplatin.

PMID- 17207962
TI  - Does the emotional go/no-go task really measure behavioral inhibition?
      Convergence with measures on a non-emotional analog.
AB  - This study tested the convergence of behavioral inhibition measures across
      emotional and non-emotional versions of the same go/no-go task in 85 college
      students. The two tasks differed only in the stimuli used for trial cues (i.e.,
      circles versus facial expressions). Moderate correlations (r=.51-.56) between
      commission errors across the emotional and non-emotional tasks support the
      construct validity of behavioral inhibition. Further, parametric manipulation of
      preceding context had comparable effects on performance on the two tasks.
      Responses were slower and more variable, commission errors were more numerous,
      and perceptual sensitivity was lower on the emotional than the non-emotional
      task. A bias for happy faces on the emotional task resulted in faster responses
      and more commission errors for happy than sad faces despite marginally greater
      sensitivity for the latter. These results suggest that the basic
      neuropsychological constructs of the original go/no-go task were preserved in the
      emotional adaptation.

PMID- 17207963
TI  - Criterion validity of the California Verbal Learning Test-Second Edition (CVLT
      II) after traumatic brain injury.
AB  - The California Verbal Learning Test-Second Edition (CVLT-II) was performed by 200
      participants, divided into moderate-severe traumatic brain injury (n=43), mild
      traumatic brain injury (n=57) and demographically matched control (n=100) groups.
      Participants with complicating premorbid histories or who scored below 15/16 on
      the CVLT-II forced choice recognition trial were excluded. There were
      statistically significant (p<.0001) effects of group status on the CVLT-II total
      recall discriminability and recognition discriminability indices. Logistic
      regression revealed that, in the classification of control versus moderate-severe
      traumatic brain injury, CVLT-II variables were accurate 66-71% overall, but false
      positive rates ranged from 49 to 54%. In conclusion, average scores on the CVLT
      II differ meaningfully between patients with various degrees of severity of
      traumatic brain injury and controls, but this test should not be used in
      isolation to determine the presence or absence of acquired memory impairment.

PMID- 17207964
TI  - Epistatic effects of polymorphisms in genes from the renin-angiotensin,
      bradykinin, and fibrinolytic systems on plasma t-PA and PAI-1 levels.
AB  - Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1)
      directly influence thrombus formation and degradation and thereby risk for
      arterial thrombosis. Activation of the renin-angiotensin system has been linked
      to the production of PAI-1 expression via the angiotensin II type 1 receptor
      (AT1R). In addition, bradykinin can induce the release of t-PA through a B2
      receptor mechanism. In the present study, we aimed to investigate the epistatic
      effects of polymorphisms in genes from the renin-angiotensin, bradykinin, and
      fibrinolytic systems on plasma t-PA and PAI-1 levels in a large population-based
      sample (n=2527). We demonstrated a strong significant interaction within genetic
      variations of the bradykinin B2 gene (P=0.002) and between ACE and bradykinin B2
      (p=0.003) polymorphisms on t-PA levels in females. In males, polymorphisms in the
      bradykinin B2 and AT1R gene showed the most strong effect on t-PA levels
      (P=0.006). In both females and males, the bradykinin B2 gene interacted with AT1R
      gene on plasma PAI-1 levels (P=0.026 and P=0.039, respectively). In addition, the
      current study found a borderline significant interaction between PAI 4G5G and ACE
      I/D on plasma t-PA and PAI-1 levels. These results support the idea that the
      interplay between the renin-angiotensin, bradykinin, and fibrinolytic systems
      might play an important role in t-PA and PAI-1 biology.

PMID- 17207965
TI  - hORFeome v3.1: a resource of human open reading frames representing over 10,000
      human genes.
AB  - Complete sets of cloned protein-encoding open reading frames (ORFs), or ORFeomes,
      are essential tools for large-scale proteomics and systems biology studies. Here
      we describe human ORFeome version 3.1 (hORFeome v3.1), currently the largest
      publicly available resource of full-length human ORFs (available at ). Generated
      by Gateway recombinational cloning, this collection contains 12,212 ORFs,
      representing 10,214 human genes, and corresponds to a 51% expansion of the
      original hORFeome v1.1. An online human ORFeome database, hORFDB, was built and
      serves as the central repository for all cloned human ORFs
      (http://horfdb.dfci.harvard.edu). This expansion of the original ORFeome resource
      greatly increases the potential experimental search space for large-scale
      proteomics studies, which will lead to the generation of more comprehensive
      datasets.

PMID- 17207966
TI  - The postnatal maternal environment influences diabetes development in nonobese
      diabetic mice.
AB  - When nonobese-diabetic (NOD) mouse embryos were implanted into pseudopregnant
      mothers of a nonautoimmune mouse strain, the progeny had a reduced type 1
      diabetes (T1D) incidence, suggesting that transmission of maternal autoantibodies
      is important for T1D development. Whether eliminating islet autoantibody
      transmission in utero, or postnatally (through milk), prevented T1D is unknown.
      Herein, we show that fostering newborn NOD mice on B-cell deficient NOD.Igmu-/-
      dams does not prevent T1D, demonstrating that postnatally transmitted islet
      autoantibodies are not required for disease pathogenesis. Additionally, NOD.Igmu
      /- mice reared on NOD dams did not develop T1D, indicating that autoantibody
      transmission to B-cell deficient NOD neonates is insufficient to trigger T1D.
      Interestingly, newborn NOD mice that were reared by ICR (but not NOD or C57BL/6)
      dams had reduced T1D incidence, although not as reduced as that reported after
      embryo transfer to ICR mice, suggesting that both prenatal and postnatal factors
      contribute to the observed reduction in T1D incidence. Thus, NOD mice have
      different risks for developing T1D depending on the strain of their foster
      mother, and both prenatal and postnatal maternal factors, other than islet
      autoantibodies, influence their T1D incidence. The results may be relevant for
      understanding the increasing incidence of T1D and designing interventions.

PMID- 17207967
TI  - Caveolins bind to (Na+, K+)/H+ exchanger NHE7 by a novel binding module.
AB  - NHE7 was identified as the first mammalian organelle-membrane type (Na+, K+)/H+
      exchanger that may contribute to the ion homeostasis in the trans-Golgi network
      (TGN) and endosomes. Here we show that caveolins directly bind to the C-terminal
      extension of NHE7 by an unconventional binding-module. NHE7 is partly associated
      with caveolae/lipid raft fractions, and heterologous expression of caveolin
      dominant-negative mutants as well as cholesterol depriving drugs diminished such
      associations. In contrast to the wild type NHE7, a deletion mutant lacking the C
      terminal extension was predominantly detected in non-caveolae/lipid rafts. We
      further show that a small fraction of NHE7 is targeted to the cell surface and
      subsequently internalized. Endocytosis of NHE7 was efficiently inhibited by
      pharmacological maneuvers that block clathrin-dependent endocytosis, whereas
      dominant-negative caveolin mutants or methyl beta-cyclodextrin did not affect
      NHE7-internalization. Thus, NHE7 associates with both caveolae/lipid rafts and
      non-caveolae/lipid raft, and the two pools likely exhibit separate dynamics.

PMID- 17207968
TI  - Community screening for psychotic-like experiences and other putative antecedents
      of schizophrenia in children aged 9-12 years.
AB  - Prospective longitudinal investigations are needed to identify causal processes
      leading to schizophrenia. However, there is presently no cost-effective way to
      identify children who are at risk of developing schizophrenia spectrum disorders:
      Although having a family history of schizophrenia is associated with elevated
      risk for developing spectrum disorders, the majority of individuals with
      schizophrenia do not have an afflicted relative. The present study aimed to test
      the feasibility of screening a community sample of children, aged 9 to 12 years,
      to identify children who experienced a triad of putative antecedents of
      schizophrenia that had been identified from previous research, including: (1)
      speech and/or motor development lags or problems; (2) social, emotional, or
      behavioural problems; and (3) psychotic-like-experiences (PLEs). 548 children and
      264 caregivers completed questionnaires. 9.2% of boys and 4.1% of girls displayed
      the triad of antecedents. 58.9% of the children reported "certain experience" of
      one or more PLEs. The results suggest that questionnaire screening of community
      samples of children for the putative antecedents of schizophrenia spectrum
      disorders is feasible. Accuracy of identification will only be established by
      follow-up studies.

PMID- 17207969
TI  - The DNA methylation profile within the 5'-regulatory region of DRD2 in discordant
      sib pairs with schizophrenia.
AB  - Studies of discordance in monozygotic twins have demonstrated that environmental
      effects play an important role in the pathogenesis of schizophrenia. DNA
      microarray analysis has revealed upregulation of the DRD2 gene in peripheral
      blood lymphocytes of schizophrenic patients. We hypothesized that this expression
      alteration could involve the DNA (CpG) methylation status that is implicated to
      the transcription status of the gene and in this study we used bisulfited
      sequence analysis to determine the DNA methylation status of a typical CpGs
      island within the 5'-regulatory region of DRD2 in peripheral blood lymphocytes
      from 48 discordant sib pairs suffering from schizophrenia. We found that the
      methylated cytosines occurred mainly in three clusters. No statistically
      significant difference in frequency of site-specific cytosine methylation
      modification of DRD2 between patients and normal controls was found nor did we
      find any significant association between sex, age on admission or age at onset of
      schizophrenia and methylated cytosines of DRD2. Our study did not support the
      hypothesis that site-specific cytosine methylation of DRD2 plays a role in the
      psychopathology of schizophrenia.

PMID- 17207970
TI  - Hair follicle bulge: a fascinating reservoir of epithelial stem cells.
AB  - Hair follicles reconstitute themselves though the hair cycle, suggesting the
      presence of intrinsic stem cells. In contrast to the previous belief that stem
      cells reside in the bulbar region of hair follicles, stem cells were detected in
      the bulge area, a contiguous part of outer root sheath, that provides the
      insertion point for arrector pili muscle and marks the bottom of the permanent
      portion of hair follicles. The bulge cells are morphologically undifferentiated
      and slow-cycling under the normal conditions. Later, studies successively
      demonstrated that bulge cells possess stem cell properties such as high
      proliferative capacity and multipotency to regenerate not only hair follicles but
      also sebaceous glands and epidermis. Our knowledge of the bulge cell biology is
      rapidly increasing because of the identification of novel cell surface markers,
      the ability to isolate living bulge cells, and microarray analysis of multiple
      gene expression. Importantly, novel cell surface markers were identified on human
      bulge cells using precise laser capture microdissection and microarray analyses.
      Use of these markers enabled the successful enrichment of living human bulge
      cells, raising the possibility of future treatments of hair disorders using stem
      cells. Additional clinical relevance of bulge cell biology includes the
      importance of bulge cells as a gene therapy target and their possible roles in
      tumorigenesis.

PMID- 17207971
TI  - Expression of the p38 MAPK, NF-kappaB and cyclin D1 in extramammary Paget's
      disease.
AB  - BACKGROUND: The p38 mitogen-activated protein kinase (MAPK)/nuclear factor kappaB
      (NF-kappaB)/cyclin D1 signaling pathway has recently been shown to play an
      important part in the pathogenesis of many human tumors. However, the role of
      this signal transduction pathway in extramammary Paget's disease (EMPD) remains
      unknown. OBJECTIVE: This study was designed to investigate the expression of
      phosphorylated p38 MAP kinasealpha (p-p38 MAPKalpha), phosphorylated NF-kappa B
      p65 (p-NF-kappaB p65) and cyclin D1 proteins in EMPD and to evaluate the
      relationship among them. METHODS: Thirty-five tissue samples from 30 primary EMPD
      cases were analyzed by immunohistochemical staining in formalin-fixed, paraffin
      embedded tissue sections for p-p38 MAPKalpha, p-NF-kappaB p65 and cyclin D1.
      RESULTS: Among the 35 specimens of EMPD, p-p38 MAPKalpha, p-NF-kappaB p65 and
      cyclin D1 were expressed in 30, 28 and 27, respectively. Moreover, in five
      metastatic lymph node specimens, all were positive for p-p38 MAPKalpha and p-NF
      kappaB p65, four were positive for cyclin D1. There were significant correlations
      between expression of p-p38 MAPKalpha, p-NF-kappaB p65, and cyclin D1 in EMPD.
      CONCLUSION: This study provides evidence that p-p38 MAPKalpha, p-NF-kappaB p65,
      and cyclin D1 was overexpressed in EMPD, suggesting that the p38 MAPK/NF
      kappaB/cyclin D1 signaling pathway might participate in the oncogenesis of EMPD.

PMID- 17207972
TI  - Tetracycline susceptibility of the ingested Lactobacillus acidophilus LaCH-5 and
      Bifidobacterium animalis subsp. lactis Bb-12 strains during antibiotic/probiotic
      intervention.
AB  - We investigated the effects of oral therapy with doxycycline, a tetracycline
      group antibiotic, on the gastrointestinal (GI) survival and tetracycline
      susceptibility of probiotic strains Lactobacillus acidophilus LaCH-5 and
      Bifidobacterium animalis subsp. lactis Bb-12. In addition, the influence of
      doxycycline therapy on the diversity of the predominant faecal microbiota was
      evaluated by polymerase chain reaction-denaturing gradient gel electrophoresis
      (PCR-DGGE). Faecal samples from the antibiotic group (receiving antibiotics and
      probiotics) and the control group (receiving probiotics only) were analysed for
      anaerobically and aerobically growing bacteria, bifidobacteria and lactic acid
      bacteria as well as for the dominant microbiota. Although doxycycline consumption
      did not have a large impact on GI survival of the probiotics, it had a
      detrimental effect on the bifidobacteria and on the diversity of the dominant
      faecal microbiota. A higher proportion of tetracycline-resistant anaerobically
      growing bacteria and bifidobacteria was detected in the antibiotic group than in
      the control group. Several antibiotic group subjects had faecal B. animalis
      subsp. lactis Bb-12-like isolates with reduced tetracycline susceptibility. This
      was unlikely to be due to the acquisition of novel tetracycline resistance
      determinants, since only tet(W), which is also present in the ingested B.
      animalis subsp. lactis Bb-12, was found in the resistant isolates. Thus,
      concomitant ingestion of probiotic L. acidophilus LaCH-5 and B. animalis subsp.
      lactis Bb-12 with the antibiotic did not generate a safety risk regarding the
      possible GI transfer of tetracycline resistance genes to the ingested strains.

PMID- 17207973
TI  - Protein-coated beta-ferric hydrous oxide particles. An electrokinetic and
      electrooptic study.
AB  - Using microelectrophoresis and electric light scattering techniques, we
      investigated the adsorption characteristics, surface coverage and surface
      electric parameters of superstructures from two isoforms of plastocyanin, PCa and
      PCb, in an oxidized state adsorbed on beta-ferric hydrous oxide particles. The
      surface electric charge and electric dipole moments of the composite particles
      and the thickness of the protein adsorption layer are determined in a wide pH
      range, at different ionic strengths and concentration ratios of PC to beta-FeOOH.
      The adsorption of the two proteins was found to shift the particles' isoelectric
      point and to alter the total electric charge and the electric dipole moments of
      the oxide particles to different extent. A "reversal" in the direction of the
      permanent dipole moment is observed at lower pH for PCb- than for PCa-coated
      oxide particles. Strict correlation is found between the changes in the
      electrokinetic charge of the composite particles and the variation in their
      "permanent" dipole moments. Data suggest that the adsorption of the proteins is
      driven by electrostatic and/or hydrophobic interactions with the oxide surfaces
      dependent on pH. The adsorption behaviour is consistent with the involvement of
      the "eastern" and "northern" patches of the plastocyanin molecules in their
      adsorption on the oxide surfaces that are differently charged depending on pH.

PMID- 17207974
TI  - Langmuir and Langmuir-Blodgett films of proline-rich N-terminal domain peptide of
      gamma-zein.
AB  - The proline-rich N-Terminal domain peptides of gamma-zein (VHLPPP)(n) with n=1
      and 3 (peptides I and II) are shown to form stable Langmuir films at air/water
      interface and the films have been characterized using surface pressure-molecular
      area (pi-A), surface potential-molecular area (DeltaV-A) isotherms, respectively.
      The longer peptide sequence does not show dramatic increase in surface or
      interfacial properties suggesting that the minimum length of n=1 is sufficient to
      achieve the necessary surface properties. Brewster angle micrographs also agreed
      with these results. The high surface-active nature of the peptide suggests a
      fairly non-polar character at air/water interface and at solid/air interface when
      coated expresses a high surface energy. Additives such as isopropyl alcohol (IPA)
      and polyvinyl alcohol (PVA) with the peptides showed more homogenous films at the
      air/water interface and also improved mechanical and tensile properties. The
      organized assembly of peptide I at the air/water and solid/air interface suggests
      that even thin layer of the peptide could play an important role in coating the
      inner surface of protein body membrane in storage proteins. Composite films of
      such short peptides with biocompatible polymers may find applications as surface
      coatings and in biomaterials.

PMID- 17207975
TI  - Solubilization of supported lipid membranes by octyl glucoside observed by time
      lapse atomic force microscopy.
AB  - Detergents are very useful for the purification of membrane proteins. A good
      detergent for protein extraction has to prevent denaturation by unfolding, and to
      avoid aggregation. Therefore, gaining access to the mechanism of biomembranes'
      solubilization by detergents is crucial in biochemical research. Among the wide
      range of detergents used to purify membrane proteins, n-octyl beta-D
      glucopyranoside (OG) is one of the most important as it can be easily removed
      from final protein extracts. Here, we used real-time atomic force microscopy
      (AFM) imaging to visualize the behavior of a model supported lipid bilayer in the
      presence of OG. Two kinds of supported model membranes were prepared by fusion of
      unilamellar vesicles: with an equimolar mixing of
      dioleoylphosphatidylcholine/dipalmitoylphosphatidylcholine (DOPC/DPPC) or with
      DPPC alone. Time-lapse AFM experiments evidenced that below its critical micelle
      concentration (CMC), OG was not able to solubilize the bilayer but the gel DPPC
      domains were instantly dissolved into the DOPC matrix. This result was
      interpreted as a disorganization of the DPPC molecular packing induced by OG.
      When membranes were incubated with OG at concentrations higher than CMC, the
      detergent immediately provoked the complete and immediate desorption of the whole
      bilayer for both compositions: DPPC and DOPC/DPPC. After a while, some patches
      appeared onto the bare mica surface. This redeposition activity, together with
      fusion events, progressively led to the recovery of a continuous bilayer. These
      results provide a new insight on the unique properties of OG employed in membrane
      reconstitution protocols.

PMID- 17207976
TI  - The surface energy of various biomaterials coated with adhesion molecules used in
      cell culture.
AB  - This study calculates the surface energy of polystyrene tissue culture plastic,
      silicon, silicon dioxide and indium tin oxide, all of which have applications in
      tissue culture. The adhesion molecules: collagen, fibronectin, poly-L-ornithine
      and poly-D-lysine, were coated onto these various surfaces, and the surface
      energy of the coated substrates calculated. Coating with fibronectin was found to
      produce a monopolar acidic surface while poly-D-lysine, poly-L-ornithine and
      collagen coatings were found to produce monopolar basic surfaces. The calculated
      surface energy components of the coated materials were then used to give a
      quantitative determination of the magnitude of their hydrophobicity. It was
      concluded that collagen, polylysine and polyornithine could provide a hydrophobic
      or hydrophilic surface depending on the underlying substrates they were coated
      on. The measurement obtained for fibronectin, unlike the other adhesion
      molecules, was independent of the underlying surface and remained hydrophobic on
      all substrates tested. Wetting experiments were carried out on the coated
      substrates, using the tissue culture medium Dulbeccos modified eagles medium,
      both containing and not containing serum proteins, and saline solution. These
      liquids that are commonly used in tissue culture, were then used to provide
      information how these liquids behave on various substrates coated with the
      adhesion molecules. Results show that fibronectin coated surfaces represent the
      most phobic surface for all three liquids. The findings of this study can be used
      in cell manipulation studies and provide a valuable data set for the biomedical
      and research industries.

PMID- 17207977
TI  - Glyco-acrylate copolymers for bilayer tethering on benzophenone-modified
      substrates.
AB  - Model biological membranes are becoming increasingly important for studying
      fundamental biophysical phenomena and developing membrane-based devices. To
      address the anticipated problem of non-physiological interactions between
      membrane proteins and substrates seen in "solid-supported lipid bilayers" that
      are formed directly on hydrophilic substrates, we have developed a polymer
      tethered lipid bilayer system based on a random copolymer with multiple lipid
      analogue anchors and a glyco-acrylate backbone. This system is targeted at
      applications that, most importantly, require stability and robustness since each
      copolymer has multiple lipid analogues that insert into the bilayer. We have
      combined this copolymer with a flexible photochemical coupling scheme that
      covalently attaches the copolymer to the substrate. The Langmuir isotherms of
      mixed copolymer/free lipid monolayers measured at the air-water interface
      indicate that the alkyl chains of the copolymer lipid analogues and the free
      lipids dominate the film behavior. In addition, no significant phase transitions
      are seen in the isotherms, while hysteresis experiments confirm that no
      irreversible states are formed during the monolayer compression. Isobaric creep
      experiments at the air-water interface and AFM experiments of the transferred
      monolayer are used to guide processing parameters for creating a fluid,
      homogeneous bilayer. Bilayer homogeneity and fluidity are monitored using
      fluorescence microscopy. Continuous bilayers with lateral diffusion coefficients
      of 0.6 microm(2)/s for both leaflets of the bilayer are observed for a 5%
      copolymer system.

PMID- 17207978
TI  - Antibody immobilization to phospholipid polymer layer on gold substrate of quartz
      crystal microbalance immunosensor.
AB  - To modify gold electrode for immunosensor to construct an artificial cell
      membrane structure, water-soluble amphiphilic phospholipid polymer, poly[2
      methacryloyloxyehtyl phosphorylcholine-co-n-butyl methacrylate-co-p
      nitrophenyloxycarbonyl poly(ethylene glycol) methacrylate (PMBN)] was applied.
      The polymer had active ester groups for immobilization of biomolecules and it was
      converted partially to thiol groups for binding to gold substrates. The partially
      thiolated PMBN was adsorbed on a gold electrode of quartz crystal microbalance
      (QCM). Surface characterization of adsorbed PMBN layers was thoroughly
      investigated with reflectance anisotropy spectroscopy, ellipsometry spectroscopy,
      dynamic contact angle and X-ray photoelectron spectroscopy measurements. Among
      several PMBN, having different degree of thiolation, it was concluded that 21.5%
      thiolated PMBN layer had the most well-ordered phosphorylcholine groups in its
      outer surface. The proteins adsorption test revealed that the phosphorylcholine
      group on the outer side of PMBN layers, which was substituted their active ester
      groups by glycine, showed suppress the non-specific adsorption of proteins, such
      as bovine serum albumin and gamma-globulin. Also, through antigen-antibody
      binding evaluation, the anti-C-reactive protein antibody immobilized on the PMBN
      surface worked well and it was confirmed that denaturation of the antibody on the
      PMBN layers was hardly occurred in spite of 60 days storage at 4 degrees C. The
      antibody conjugated phospholipid polymer layer with well-ordered
      phosphorylcholine group could be outstanding functional membrane for biomedical
      diagnostic devices without non-specific binding and reduction of immunologic
      activity of immobilized antibody.

PMID- 17207979
TI  - Electro-optical investigations of the dipole moments of nanoparticles.
AB  - In this paper, the electric properties of polar nanoparticles are examined.
      Special attention is paid to the terminology, classification and the physical
      bases of the different electric moments. A short history of the electro-optic
      studies of dipole moments of nanoparticles and the electro-optic Conferences is
      presented. The connection of the polar properties with the particle electric
      charge is considered. The potential of the colloid electro-optics for studying
      the properties of anisometric, anisotropic polar nanoparticles is discussed in
      details. Examples of such studies are presented. A comparative analysis is made
      of the potential of dielectric, electro-optic and dielectrophoretic measurements
      for studying the electric properties, size, shape and structure of polar
      nanoparticles.

PMID- 17207980
TI  - Phenotypic and genetic diversity of rhizobia isolated from nodules of the legume
      genera Astragalus, Lespedeza and Hedysarum in northwestern China.
AB  - Twenty-nine rhizobial isolates from root nodules of the wild Legumes Astragalus,
      Lespedeza and Hedysarum growing in the northwestern region of China, were
      characterized by numerical taxonomy, RFLP and sequencing of PCR-amplified 16S
      rDNA genes, and cross-nodulation with selected Legume species. Based on the
      results from numerical taxonomy, the isolates could be divided into two main
      groups (Clusters 1 and 2) and some single isolates at 82% similarity. CLuster 1
      contained six isolates from Astragalus, Lespedeza and Hedysarum spp. Cluster 2
      consisted of nine isolates from Astragalus and Hedysarum species. The
      phytogenetic analysis based on 16S rRNA gene sequences showed that SH199,
      representing cluster 1, belonged to the Rhizobium-Agrobacterium group, and
      SH290B, representing cluster 2, was closely related to R. galegae and R.
      huautlense.

PMID- 17207981
TI  - Optimization of laccase production from a novel strain-Streptomyces psammoticus
      using response surface methodology.
AB  - Response surface methodology was employed for the optimization of different
      nutritional and physical parameters for the production of laccase by the
      filamentous bacteria Streptomyces psammoticus MTCC 7334 in submerged
      fermentation. Initial screening of production parameters was performed using a
      Plackett - Burman design and the variables with statistically significant effects
      on laccase production were identified. Incubation temperature, incubation period,
      agitation rate, concentrations of yeast extract, MgSO(4)7H(2)O, and trace
      elements were found to influence laccase production significantly. These
      variables were selected for further optimization studies using a Box-Behnken
      design. The statistical optimization by response surface methodology resulted in
      a three-fold increase in the production of laccase by S. psammoticus MTCC 7334.

PMID- 17207982
TI  - Intercellular colonization and growth promoting effects of Methylobacterium sp.
      with plant-growth regulators on rice (Oryza sativa L. Cv CO-43).
AB  - The Methylobacterium sp. strain NPFM-SB3, isolated from Sesbania rostrata stem
      nodules possessed nitrogenase activity and nodA genes. Pure culture of NPFM-SB3
      strain produced indole-3-acetic acid, cytokinins and on inoculation to rice
      plants resulted in numerous lateral roots. Inoculation of synthetic auxins 2,4
      dichlorophenoxy acetic acid, naphthalene acetic acid or flavonoids naringenin and
      dihydroxy-4-methoxyisoflavone individually or to bacterial inoculated rice
      seedlings improved the plant growth and lateral root formation under hydroponic
      condition. The formation of nodule-like structure and nitrogenase activity which
      is purely auxin dependent was observed in 2,4-dichlorophenoxy acetic acid
      treatments to Methylobacterium sp. NPFM-SB3 inoculated rice plants. The rhizobia
      entered through fissures formed due to lateral root emergence and spread
      intercellularly in the nodular structures concluded that the effect of 2,4
      dichlorophenoxy acetic acid treatment for rice seedlings grown under gnotobiotic
      conditions is to create a niche in which these bacteria can grow.

PMID- 17207983
TI  - Dynamics of changes in methanogenesis and associated microflora in a flooded
      alluvial soil following repeated application of dicyandiamide, a nitrification
      inhibitor.
AB  - Influence of repeated application of the nitrification inhibitor dicyandiamide
      (DCD), on CH(4) production and associated microflora in a flooded alluvial soil,
      was investigated in a laboratory incubation study. Application of DCD at the time
      of soil incubation resulted in a substantial reduction in CH(4) production (31%
      over that of untreated control). Second repeat application of DCD, on the
      contrary, annulled the inhibitory effect on CH(4) production, restoring it to the
      level of unamended soil. Application of the third dose of DCD maintained CH(4)
      production almost to the same extent as that of second application. The
      alleviation of the initial inhibitory effect of DCD on CH(4) production was
      linked to the enhanced degradation of DCD following its repeated application to
      the flooded soil. Admittedly, abatement of the initial inhibitory effect of DCD
      on CH(4) production in soil repeatedly amended with DCD was also related to the
      inhibition of CH(4)-oxidizing bacterial population and noticeable stimulation of
      heterotrophic bacterial population. Results suggest that repeat application of
      DCD with fertilizer-N to flooded rice soils might not be effective in controlling
      CH(4) production under field condition.

PMID- 17207984
TI  - The microbial ecology of a high-temperature near-neutral spring situated in
      Rotorua, New Zealand.
AB  - A combination of both culture and culture-independent techniques were used to
      investigate the microbial ecology of a near-neutral, high-temperature hot spring
      (designated AQ1) in Rotorua, New Zealand. The active microbial members of the
      community were targeted by analyzing biofilms that developed on surfaces
      incubated in situ in AQ1. Colonization of surfaces was rapid as indicated by ATP
      assay and microscopic observation. DNA-based analysis of both colonized surfaces
      and pool water from AQ1 revealed an exclusively archaeal community. Different
      colonization patterns were observed on glass slides incubated near the pool
      surface or at depth. Slides incubated at the surface were colonized exclusively
      by Pyrobaculum species, while at greater depth a novel coccus was also observed
      and detected by DGGE. Sequence analysis revealed the coccus was related to
      Aeropyrum pernix. Two microorganisms were isolated from AQ1 pool water, namely
      Ignisphaera aggregans AQ1.S1T and a species of Pyrobaculum, isolate AQ1.S2.

PMID- 17207985
TI  - Assessment of bacterial community structure in a long-term copper-polluted ex
      vineyard soil.
AB  - The influence of long-term copper contamination on the diversity of bacterial
      communities was investigated in an ex-vineyard soil. Two sites of the same area
      but exhibiting different 3-fold exchangeable copper (Ex-Cu) concentrations were
      analysed. Culturable bacterial community structure was assessed using a variety
      of approaches: determination of culturable bacteria number, analyses of 132
      isolates, and denaturing gradient gel lectrophoresis (DGGE) patterns of bacterial
      biomass grown on agar plates and of soil DNA. There was no significant difference
      in the number of total heterotrophs at the two sites, whereas the percentage of
      fast-growing bacteria growing in 1 day, was lower at the site with the higher Ex
      Cu content. A high percentage of Cu-tolerant bacteria was found in both sites (63
      70%) and it was relatively independent of the Cu content. Shifts in species
      composition of the culturable bacterial community were detected by analysing
      isolates from the two soils, Gram-positive bacteria prevailed in the less
      polluted soil while Gram-negative bacteria in the more-polluted soil. Each sample
      site had a community with a different metal resistance pattern. Our study seems
      to indicate that in this soil ecosystem, copper influenced the culturable
      bacterial communities, affecting the structural diversity and altering some of
      the metal resistance of the microorganisms. The Sorensen similarity index
      calculated on DGGE profiles of 16S rDNA of total and culturable bacterial
      communities indicated a different species composition at the two sites, although
      both sites had the same biodiversity degree and different dominance.

PMID- 17207986
TI  - Antibacterial activity, structure and CMC relationships of alkanediyl alpha,omega
      bis(dimethylammonium bromide) surfactants.
AB  - Some alpha,omega-alkanediyl bis-dimethylammonium bromide compounds (gemini
      surfactants) referred as "m-s-m" have been synthesized, purified and
      characterized by usual spectroscopic methods. These compounds have been screened
      for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa and
      Staphylococcus aureus. Their activity was compared. The compounds tested showed
      excellent in vitro antibacterial activity against Staphylococcus aureus ranging
      from 1.5 to 20 microg/ml and had variable activity against E. coli with minimum
      minimum inhibitory concentration (MIC) of 50 microg/ml. These compounds are less
      active against P. aeruginosa. On the other hand, contrary to the antibacterial
      activity of these products against S. aureus, a relation between the MIC and the
      critical micellar concentration (CMC) was found and relationship between chain's
      Length and antibacterial activity was found.

PMID- 17207988
TI  - Performance of a low cost MBT prior to landfilling: study of the biological
      treatment of size reduced MSW without mechanical sorting.
AB  - In France, the interest in Mechanical Biological Treatment (MBT) prior to
      landfilling is actually growing. In the absence of acceptance criteria for the
      waste to be landfilled, an alternative to the intensive, high-technology MBT can
      only find its place in the French context if it shows substantial benefits from
      an environmental, economic or operational point of view. This paper presents an
      experiment of low-cost MBT of size reduced MSW without material splitting. The
      performance of an experimental, pilot-scale mechanical and biological treatment
      process has been studied on 37.5 Mg of raw municipal solid waste. The mechanical
      process has been kept simple with only coarse shredding and no material recovery.
      The biological treatment, which was a low-cost forced aeration process, was
      monitored for 25 weeks. The biogas production potential of the waste was reduced
      by 90% to 19 NL kgDM(-1). The initial AT4 index of 82.9 mg O2 gDM(-1) decreased
      to 16.0 mg O2 gDM(-1). After 25 weeks of aerobic treatment, the dry mass loss
      reached 37%, while the mass of waste going to landfill was reduced by 28%. The
      average performances of the process were explained by the biological process
      itself, which was not optimal, and also by the characteristics of the input
      waste. The high particle size of the treated waste and the high content of slowly
      biodegradable matter (such as paper and cardboard) may both be significant
      drawbacks for the biological stabilisation of waste.

PMID- 17207989
TI  - Single-molecule studies of nucleic acid motors.
AB  - Nucleic acid motors comprise a variety of structurally, mechanistically and
      functionally very different enzymes. These motor proteins have in common the
      ability to directionally move DNA or RNA, or to move along DNA or RNA using a
      chemical energy source such as ATP. Recently, it became possible to study the
      action of a single motor on single DNA or RNA molecules in real time; this has
      provided unprecedented insight into the behavior and mechanism of these motors.
      As a result, the past few years have witnessed an enormous increase in such
      single-molecule studies of a variety of different motor systems. Particular
      highlights have included the investigation of the sequence-dependent behavior and
      helical tracking of motors, and the attainment of the ultimate (i.e. single base
      pair) resolution, which enables the detection of individual single base motor
      steps.

PMID- 17207990
TI  - Regulation of the CYP27B1 5'-flanking region by transforming growth factor-beta
      in ROS 17/2.8 osteoblast-like cells.
AB  - The biologically active form of vitamin D, 1,25-dihydroxyvitamin D(3)
      (1,25(OH)(2)D(3)), regulates osteoblast proliferation and differentiation.
      Production of 1,25(OH)(2)D(3) is catalysed by the enzyme 25-hydroxyvitamin D(3)
      1alpha-hydroxylase (CYP27B1). Though highly expressed in the kidney, the CYP27B1
      gene is also expressed in non-renal tissues including bone. It is hypothesised
      that local production of 1,25(OH)(2)D(3) by osteoblasts plays an autocrine or
      paracrine role. The aim of this study was to investigate what factors regulate
      expression of the CYP27B1 gene in osteoblast cells. ROS 17/2.8 osteoblast cells
      were transiently transfected with plasmid constructs containing the 5'-flanking
      sequence of the human CYP27B1 gene fused to a luciferase reporter gene. Cells
      were treated with either parathyroid hormone (PTH), 1,25(OH)(2)D(3), transforming
      growth factor-beta (TGF-beta) or insulin-like growth factor-1 (IGF-1) and
      luciferase activity was measured 24h later. The results showed that
      1,25(OH)(2)D(3) did not alter expression of the reporter construct, however
      treatment with PTH, IGF-1 and TGF-beta decreased expression by 18, 53 and 58%
      respectively. The repressive action of TGF-beta was isolated to the region
      between -531 and -305bp. These data suggest that expression of the 5'-flanking
      region for the CYP27B1 gene in osteoblast cells may be regulated differently to
      that previously described in kidney cells.

PMID- 17207991
TI  - Synthesis and biological evaluation of a 3-positon epimer of 1alpha,25-dihydroxy
      2beta-(3-hydroxypropoxy)vitamin D3 (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)], possesses
      a hydroxypropoxy substituent at the 2beta-position of 1,25(OH)(2)D(3). ED-71 has
      potent biological effects on bone and is currently under phase III clinical
      studies for bone fracture prevention. It is well-known that the synthesis and
      secretion of parathyroid hormone (PTH) is regulated by 1,25(OH)(2)D(3).
      Interestingly, during clinical development of ED-71, serum intact PTH in
      osteoporotic patients did not change significantly upon treatment with ED-71. The
      reason remains unclear, however. Brown et al. reported that 3-epi
      1,25(OH)(2)D(3), an epimer of 1,25(OH)(2)D(3) at the 3-position, shows equipotent
      and prolonged activity compared to 1,25(OH)(2)D(3) at suppressing PTH secretion.
      Since ED-71 has a bulky hydroxypropoxy substituent at the 2-position,
      epimerization at the adjacent and sterically hindered 3-position might be
      prevented, which may account for its weak potency in PTH suppression observed in
      clinical studies. We have significant interest in ED-71 epimerization at the 3
      position and the biological potency of 3-epi-ED-71 in suppressing PTH secretion.
      In the present studies, synthesis of 3-epi-ED-71 and investigations of in vitro
      suppression of PTH using bovine parathyroid cells are described. The inhibitory
      potency of vitamin D(3) analogs were found to be 1,25(OH)(2)D(3)>ED-71> or =3-epi
      1,25(OH)(2)D(3)>>3-epi-ED-71. ED-71 and 3-epi-ED-71 showed weak activity towards
      PTH suppression in our assays.

PMID- 17207992
TI  - Transgenic expression of the human Vitamin D receptor (hVDR) in the duodenum of
      VDR-null mice attenuates the age-dependent decline in calcium absorption.
AB  - 1,25(OH)(2)D(3) regulates calcium homeostasis through its actions in the
      intestine, bone, and kidney. These actions are mediated through the VDR. To
      determine if VDR's actions in the proximal small intestine can sufficiently
      restore calcium homeostasis, we generated transgenic mice expressing hVDR
      exclusively in the duodenum of mVDR-null mice by using the adenosine deaminase
      enhancer (hVDR+/mVDR-null). Unlike wild-type mice, hVDR+/mVDR-null mice express
      hVDR and VDR target genes only in the proximal small intestine. Despite having
      functional hVDR in the proximal small intestine, hVDR+/mVDR-null mice were
      hypocalcaemic when fed a normal rodent diet at weaning, like mVDR-null mice fed
      the same diet. The hypocalcemia in these mice is prevented if they are given the
      rescue diet before weaning. However, when 90-day-old rachitic mice were fed a
      rescue diet, serum calcium improved in hVDR+/mVDR-null mice, but not in mVDR-null
      mice. In conclusion, transgenic hVDR in the proximal small intestine of
      hVDR+/mVDR-null mice was transcriptionally active and regulated calcium
      absorption, but VDR actions elsewhere in the intestine are probably necessary to
      support adequate calcium homeostasis. In addition, hVDR+/mVDR-null mice responded
      better to the late rescue diet suggesting that expression of VDR in the proximal
      small intestine protected the calcium absorbing machinery from age-dependent
      decline.

PMID- 17207993
TI  - Evaluation of C-2-substituted 19-nor-1alpha,25-dihydroxyvitamin D3 analogs as
      therapeutic agents for prostate cancer.
AB  - 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) is known to inhibit the
      proliferation and invasiveness of prostate cancer cells. However,
      1alpha,25(OH)(2)D(3) can cause hypercalcemia and is not suitable as a therapeutic
      agent. 19-Nor-vitamin D derivatives are known to be less calcemic when
      administered systemically. In order to develop more potent anti-cancer agents
      with less calcemic side effect, we therefore utilized (3)H-thymidine
      incorporation as an index for cell proliferation and examined the
      antiproliferative activities of nine C-2-substituted 19-nor-1alpha,25(OH)(2)D(3)
      analogs in the immortalized PZ-HPV-7 normal prostate cell line. Among the nine
      analogs we observed that the substitution with 2alpha- or 2beta-hydroxypropyl
      group produced two analogs having antiproliferative potency that is approximately
      500- to 1000-fold higher than 1alpha,25(OH)(2)D(3). The (3)H-thymidine
      incorporation data were supported by the cell counting data after cells were
      treated with 1alpha,25(OH)(2)D(3), 19-nor-2alpha-(3-hydroxypropyl)
      1alpha,25(OH)(2)D(3) or 19-nor-2beta-(3-hydroxypropyl)-1alpha,25(OH)(2)D(3) for 7
      days. 19-Nor-2alpha-(3-hydroxypropyl)-1alpha,25(OH)(2)D(3) and 19-nor-2beta-(3
      hydroxypropyl)-1alpha,25(OH)(2)D(3) were also shown to be about 10-fold more
      active than 1alpha,25(OH)(2)D(3) in cell invasion studies using prostate cancer
      cells. In conclusion, a substitution at the C-2 position of 19-nor
      1alpha,25(OH)(2)D(3) molecule with a hydroxypropyl group greatly increased the
      antiproliferative and anti-invasion potencies. Thus, these two analogs could be
      developed to be effective therapeutic agents for treating early and late stages
      of prostate cancer.

PMID- 17207994
TI  - Role of oncoprotein growth factor independent-1 (GFI1) in repression of 25
      hydroxyvitamin D 1alpha-hydroxylase (CYP27B1): a comparative analysis in human
      prostate cancer and kidney cells.
AB  - 1,25-Dihydroxyvitamin D (1,25D) inhibits growth of prostate cancer cells and has
      been proposed to play a protective role in prostate cancer. However, 25
      hydroxyvitamin D 1alpha-hydroxylase (CYP27B1), the enzyme responsible for the
      cellular synthesis of 1,25D, is repressed in prostate cancer cells. Recently, we
      have identified a role for the transcription factor, Growth Factor Independent-1
      (GFI1) in the repression of the CYP27B1 gene in human prostate cancer cell lines.
      GFI1 is known to form a large protein complex with co-repressors that recruit
      histone deacetylases. We have proposed a model for the molecular repression of
      CYP27B1 gene expression. The formation of such a repressive complex on the
      inhibitory domain of the CYP27B1 gene in prostate cancer cells could lead to the
      silencing of gene expression either by inactivating nearby enhancer or proximal
      promoter domains and lead to cancer progression by reducing local production of
      1,25D. These studies demonstrate that GFI1 may play a significant role in the
      down regulation of endogenous production of 1,25D in prostate cancer cells and
      could provide a novel insight to future diagnosis and treatment.

PMID- 17207996
TI  - Applications of computational fluid dynamics (CFD) in the modelling and design of
      ventilation systems in the agricultural industry: a review.
AB  - The application of computational fluid dynamics (CFD) in the agricultural
      industry is becoming ever more important. Over the years, the versatility,
      accuracy and user-friendliness offered by CFD has led to its increased take-up by
      the agricultural engineering community. Now CFD is regularly employed to solve
      environmental problems of greenhouses and animal production facilities. However,
      due to a combination of increased computer efficacy and advanced numerical
      techniques, the realism of these simulations has only been enhanced in recent
      years. This study provides a state-of-the-art review of CFD, its current
      applications in the design of ventilation systems for agricultural production
      systems, and the outstanding challenging issues that confront CFD modellers. The
      current status of greenhouse CFD modelling was found to be at a higher standard
      than that of animal housing, owing to the incorporation of user-defined routines
      that simulate crop biological responses as a function of local environmental
      conditions. Nevertheless, the most recent animal housing simulations have
      addressed this issue and in turn have become more physically realistic.

PMID- 17207995
TI  - Therapeutic role and potential mechanisms of active Vitamin D in renal
      interstitial fibrosis.
AB  - Vitamin D, especially its most active metabolite 1,25-dihydroxyvitamin D(3) or
      calcitriol, is essential in regulating a wide variety of biologic processes, such
      as calcium homeostasis, immune modulation, cell proliferation and
      differentiation. Clinical studies show that the circulating level of calcitriol
      is substantially reduced in patients with chronic renal insufficiency.
      Administration of active Vitamin D results in significant amelioration of renal
      dysfunction and fibrotic lesions in various experimental models of chronic kidney
      diseases. Active Vitamin D elicits its renal protective activity through multiple
      mechanisms, such as inhibiting renal inflammation, regulating renin-angiotensin
      system and blocking mesangial cell activation. Recent studies indicate that
      calcitriol induces anti-fibrotic hepatocyte growth factor expression, which in
      turn blocks the myofibroblastic activation and matrix production in interstitial
      fibroblasts. Furthermore, in vivo and in vitro studies demonstrate that active
      Vitamin D effectively blocks tubular epithelial to mesenchymal transition (EMT),
      a phenotypic conversion process that plays a central role in the evolution of
      renal interstitial fibrosis. Together, it is becoming increasingly clear that a
      high level of active Vitamin D may be obligatory in the maintenance of normal
      kidney structure and function. Thus, supplementation of active Vitamin D could be
      a rational strategy for the therapeutics of chronic kidney diseases.

PMID- 17207997
TI  - Effect of long-term application of manure and fertilizer on biological and
      biochemical activities in soil during crop development stages.
AB  - A field experiment was conducted to investigate the effect of six long-term (34
      year) fertilizer and farmyard manure (FYM) treatments (Control, N, NP, NPK,
      NPK+S, NPK+FYM) and three physiological stages of wheat growth on the microbial
      biomass carbon (MBC), nitrogen (MBN) and dehydrogenase, mineralizable N and
      phosphatase activities in soil. It was found that a balanced application of
      NPK+FYM gave the highest values for the measured parameters and lowest at the
      control. Values were generally highest at tillering, followed by the flowering
      and dough stages. A significant positive interaction between fertilizer
      treatments and physiological stages of wheat growth was observed, being highest
      at maximum tillering due to application of NPK+FYM. Stepwise regressions have
      revealed that grain yield of wheat was significantly associated with
      mineralizable N at tillering (R(2)=0.80), MBC at flowering (R(2)=0.90) and
      alkaline phosphatase activity (R(2)=0.70) at dough stages of wheat growth.

PMID- 17207998
TI  - Development of an improved anaerobic filter for municipal wastewater treatment.
AB  - Development of an improved reactor configuration of anaerobic filter was carried
      out for the elimination of clogging of filter media. The experiments over
      different hydraulic retention times (HRTs) indicated that the HRT of 12 h was the
      most appropriate one for the system studied while treating the municipal
      wastewater, which resulted 90% and 95% BOD and COD reduction, respectively.
      Reduction up to 95% in suspended solids concentration could be achieved without
      any pretreatment. The specific biogas yield obtained was 0.35 m(3) CH(4)/kgCODr
      with 70% of CH(4) content in the biogas generated from the system at the HRT of
      12 h. Operational problems such as clogging of filter media were not observed
      throughout the period of study over 600 d.

PMID- 17207999
TI  - Biotechnological conversion of agro-industrial wastewaters into biodegradable
      plastic, poly beta-hydroxybutyrate.
AB  - Waste activated sludge generated from a combined dairy and food processing
      industry wastewater treatment plant was evaluated for its potential to produce
      biodegradable plastic, poly beta-hydroxybutyric acid (PHB). Deproteinized jowar
      grain-based distillery spentwash yielded 42.3% PHB production (w/w), followed by
      filtered rice grain-based distillery spentwash (40% PHB) when used as substrates.
      Addition of di-ammonium hydrogen phosphate (DAHP) resulted in an increase in PHB
      production to 67% when raw rice grain-based spentwash was used. Same wastewater,
      after removal of suspended solids by filtration and with DAHP supplementation
      resulted in lower PHB production (57.9%). However, supplementing other wastes
      with DAHP led to a substantial decrease in PHB content in comparison to what was
      observed in the absence of DAHP.

PMID- 17208000
TI  - Muscle length and lengthening velocity in voluntary crouch gait.
AB  - The purpose of this study was to explore how origin-insertion length and
      lengthening velocity of hamstring and psoas muscle change as a result of crouch
      gait. The second purpose was to study the effect of changes in walking speed, in
      crouch, on muscle lengths and velocities. Eight healthy female subjects walked on
      a treadmill both normally and in crouch. In the crouch condition, subjects walked
      at three different walking speeds. 3D kinematic data were collected and muscle
      lengths and velocities were calculated using musculoskeletal modeling. It was
      found that voluntary walking in crouch resulted in shorter psoas length compared
      to normal, but not in shorter hamstrings length. Moreover, crouch gait did not
      result in slower muscle lengthening velocities compared to normal gait. These
      results do not support the role of hamstrings shortness or spasticity in causing
      crouch gait. Decreasing walking speed clearly reduced muscle lengths and
      lengthening velocities. Therefore, patients with short or spastic muscles are
      more likely to respond by walking slower than by walking in crouch. Also,
      differences in walking speed should be avoided as a confounding factor when
      comparing patient groups with controls.

PMID- 17208001
TI  - ATP synthase--the structure of the stator stalk.
AB  - ATP synthase synthesizes ATP from ADP and inorganic phosphate using a unique
      rotary mechanism whereby two subcomplexes move relative to each other, powered by
      a proton or sodium gradient. The non-rotating parts of the machinery are held
      together by the "stator stalk". The recent resolution of the structure of a major
      portion of the stator stalk of mitochondrial ATP synthase represents an important
      step towards a structural model for the ATP synthase holoenzyme.

PMID- 17208002
TI  - Quantitative analysis on volcanic ash surfaces: application of extended depth-of
      field (focus) algorithm for light and scanning electron microscopy and 3D
      reconstruction.
AB  - The depth-of-field mainly affects the image quality either in scanning electron
      microscopy (SEM) or conventional light microscopy. The limited depth-of-field
      handicap of microscopy imaging can be used for obtaining "optically sectioned"
      specimens by moving the object along the optical axis. In this study, multiple
      images corresponding to different object planes were taken in order to overcome
      limited depth-of-field on conventional light microscope and SEM, estimation of an
      elevation surface and 3D reconstruction of different type volcanic ash surfaces.
      We used extended depth-of-field, a fusion algorithm that combines those images
      into one single sharp composite. Because of larger depth-of-field, we got higher
      quality results even with image stacks taken by SEM with a fixed aperture in
      variable pressure mode. We calculated roughness descriptors, quadtree
      decomposition and greylevel standard deviation (sGL) and analyzed the shape of
      polar plots based on gradient analysis of constructed depth-maps. Furthermore, we
      calculated fractal dimensions of surfaces. Correlation analysis was performed to
      measure how these quantitative variables are related with different type ash
      surfaces. Roughness descriptors, quadtree decomposition, sGL and fractal
      dimension discriminate different types of volcanic ash surfaces.

PMID- 17208004
TI  - Study on the interaction between the chiral drug of propranolol and alpha1-acid
      glycoprotein by fluorescence spectrophotometry.
AB  - The interaction between the chiral drug of propranolol (PPL) and alpha1-acid
      glycoprotein (AGP, orosomucoid) has been first studied by fluorescence
      spectrophotometry. The fluorescence intensity of PPL increased due to the
      addition of AGP into PPL. The equation of Scatchard was employed to calculate the
      association constant and binding site number of the two enantiomers with AGP. The
      association constant is 2.62 x 10(5)M-1 for R-PPL and 8.57 x 10(5)M-1 for S-PPL
      and the binding site number is 0.41 for R-PPL and 1.17 for S-PPL at 17 degrees C
      respectively. The method of thermodynamics was applied to determine the binding
      type of S-PPL with AGP. The results suggested that the binding type is mainly van
      der waals force or hydrogen bond. At last the effect of three metal cations on
      the association constant and the binding site number of S-PPL with AGP was
      examined.

PMID- 17208003
TI  - Gender and age differences in expression of GABAA receptor subunits in rat
      somatosensory thalamus and cortex in an absence epilepsy model.
AB  - Absence epilepsy is more prevalent in females, but reasons for this gender
      asymmetry are unknown. We reported previously that perinatal treatment of Long
      Evans Hooded rats with the cholesterol synthesis inhibitor (CSI) AY9944 causes a
      life-long increase in EEG spike-wave discharges (SWDs), correlated with decreased
      expression of GABA(A) receptor subunit gamma2 protein levels in thalamic
      reticular and ventrobasal nuclei (SS thalamus) [Li, H., Kraus, A., Wu, J.,
      Huguenard, J.R., Fisher, R.S., 2006. Selective changes in thalamic and cortical
      GABA(A) receptor subunits in a model of acquired absence epilepsy in the rat.
      Neuropharmacology 51, 121-128]. In this study, we explored time course and gender
      different effects of perinatal AY9944 treatment on expression of GABA(A) receptor
      alpha1 and gamma2 subunits in SS thalamus and SS cortex. Perinatal AY9944
      treatment-induced decreases in GABA(A) gamma2 receptor subunits in rat SS
      thalamus and increases in SS cortex are gender and age specific. The findings
      suggest a mechanism for the higher prevalence of absence epilepsy in female
      patients.

PMID- 17208005
TI  - Comparative activity of antiemetic drugs.
AB  - Nausea and vomiting continues to be an important problem for cancer patients
      receiving chemotherapy. Chemotherapy-induced nausea and vomiting (CINV) are
      classified as acute, occurring within the first 24h, or delayed, occurring after
      the first 24h. A number of antiemetic agents are available for the management of
      nausea and vomiting, including 5-HT3-receptor-antagonists, corticosteroids, NK-1
      receptor-antagonists, dopamine-receptor antagonists, benzodiazepines,
      neuroleptics and cannabinoids. With modern antiemetic therapy, vomiting can be
      prevented in 70-80% of patients, whereas the control of nausea remains
      suboptimal. The development of acute emesis is known to depend on serotonin. The
      pathophysiology of delayed emesis is less well understood, and multiple
      mechanisms may contribute, including substance P. Here, the most recent
      developments in the antiemetic therapy, including new antiemetic drugs and the
      latest guidelines for antiemetic prophylaxis, are reviewed.

PMID- 17208006
TI  - Novel treatment strategies for malignant melanoma: a new beginning?
AB  - Malignant melanoma is one of the most common cancer types among the Caucasian
      population. While the prognosis is excellent for patients diagnosed at an early
      stage and treated by adequate surgery, unresectable or advanced metastatic
      diseases shrink the overall survival at 5 years dramatically to less than 10%.
      For disseminated malignant melanoma, the appropriate systemic medical treatment
      is still controversial. Fortunately, progress in the molecular biology and in the
      understanding of pathogenesis has been made recently and should in the near
      future translate into molecular-based therapeutic strategies. In this review, we
      briefly describe the status of current treatment strategies and existing
      standards for malignant melanoma. We will focus on the new and emerging compounds
      including recent developments of targeted therapy such as antiangiogenic and
      immunomodulatory drugs, Bcl-2 antisense therapy, raf kinase inhibitors, heat
      shock protein modulators, anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4
      monoclonal antibody and finally PARP and proteasome inhibitors.

PMID- 17208007
TI  - Liquid chromatography-tandem mass spectrometry analysis of the DNA adducts of
      aristolochic acids.
AB  - Electrophilic attack of aristolactam-nitrenium ion by the C7 position to the
      exocyclic amino group in the DNA bases led to the formation of the major adducts.
      In this study, liquid chromatography coupled with electrospray ionization tandem
      mass spectrometry was applied to the study of DNA adducts of aristolochic acid
      (AA). When DNA (bases and CT-DNA) was incubated with AA, dG-AAI, dG-AAII, dA-AAI,
      dA-AAII, dC-AAI, and dC-AAII were detected and characterized. The dC adducts of
      AA were identified for the first time. The soft ionization technology allowed
      detection of the intact DNA adducts. High-resolution MS and MS-MS capabilities of
      a quadrupole time-of-flight mass spectrometer were shown to be efficient for DNA
      adducts analysis. DNA-AA adducts showed characteristic fragmentation patterns in
      MS-MS analysis. The dissociative loss of 116 Da from the DNA-AA adducts, which
      resulted from internal hydrogen transfer and cleavage at the C-N glycosidic bond,
      provided a characteristic fragment for the structural elucidation.

PMID- 17208008
TI  - Infrared multiphoton dissociation of the siderophore enterobactin and its Fe(III)
      complex. Influence of Fe(III) binding on dissociation kinetics and relative
      energetics.
AB  - The dissociation pathways of the siderophore enterobactin and its complex with
      Fe(III) were examined using infrared multiphoton dissociation (IRMPD). Under
      experimental conditions (pH = 3.5), both compounds' electrospray spectra
      exhibited exclusively singly-charged anions. The compositions of the dissociation
      products were characterized by accurate mass measurements using Fourier transform
      ion cyclotron resonance mass spectrometry (FT-ICR MS). The primary dissociation
      channel for both species was determined to be the loss of one serine group from
      the precursor molecules. To further investigate the influence of Fe(III) binding
      on the intramolecular interactions, dissociation kinetics and relative energetics
      for the loss of this serine group were determined using the focused radiation for
      gaseous multiphoton energy-transfer (FRAGMENT) method. From the kinetic data, it
      was found that enterobactin was approximately seven times more reactive than its
      Fe(III) complex over the range of laser intensities investigated. The relative
      activation energies, however, exhibited similar values, approximately 7 kcal.mol(
      1). These results suggest that at pH = 3.5, Fe(III) interacts with only two of
      the three serine groups. The results from the present work are believed to be
      valuable for the characterization of novel siderophores as well as their
      associated metabolites and synthetic analogues.

PMID- 17208009
TI  - Functional expression of recombinant canstatin in stably transformed Drosophila
      melanogaster S2 cells.
AB  - We describe the expression and in vitro activity of recombinant canstatin from
      stably transformed Drosophila melanogaster S2 cells. Southern blot analysis
      indicated that transformed S2 cells contained multiple copies of the canstatin
      gene in the genome. Recombinant canstatin with a molecular weight of 29kDa was
      secreted into the culture medium. Recombinant canstatin was purified to
      homogeneity using a simple one-step Ni(2+) affinity fractionation. Purified
      recombinant canstatin inhibited human umbilical vein endothelial cell
      proliferation in a dose-dependent manner. The concentration at half-maximum
      inhibition (ED(50)) for recombinant canstatin expressed in stably transformed
      Drosophila S2 cells was approximately 0.37mug/ml. A maximum production level of
      76mg/l of recombinant canstatin was obtained in a T-flask culture of Drosophila
      S2 cells 6 days after induction with 0.5mM CuSO(4).

PMID- 17208010
TI  - High-level expression of human lactoferrin in the milk of goats by using
      replication-defective adenoviral vectors.
AB  - The expression of human lactoferrin in the mammary gland is an attractive
      approach to diminish its current production cost. Previous attempts to produce
      lactorferrin in the milk of transgenic animals resulted in very high cost and
      uncertain results. In this paper, we have directly infused replication-defective
      adenovirus encoding human lactoferrin cDNA into the mammary gland of goats via
      the teat canal. In this way, we obtained a high level of expressed human
      lactoferrin up to 2g/L in the milk of goats. The milk serum was collected from
      the infected mammary gland 48 h post-infection and subjected to a 10% SDS-PAGE
      and Western blotting. A approximately 80-kDa protein was visualized after viral
      vector infection. Our results demonstrate that intraductal injection of
      recombinant replication-defective adenovirus vectors may provide a very useful
      tool for large-scale production of recombinant proteins of biopharmaceutical
      interest.

PMID- 17208011
TI  - Identification and cloning of the antioxidant enzyme, glutathione peroxidase, of
      white shrimp, Litopenaeus vannamei, and its expression following Vibrio
      alginolyticus infection.
AB  - cDNA encoding glutathione peroxidase (GPx) mRNA of the white shrimp Litopenaeus
      vannamei was obtained from haemocytes by a reverse-transcription polymerase chain
      reaction (RT-PCR) and rapid amplification of cDNA (RACE) using oligonucleotide
      primers based on the GPx sequence of Homo sapiens (NM002083), Mus musculus
      (NM008160), Arabidopsis thaliana (U94495), Bos taurus (NM174770), and Capsicum
      chinense (AJ973135). The 727-bp cDNA contained an open reading frame (ORF) of 567
      bp, a 101-bp 5'-untranslated region, and a 59-bp 3'-untranslated region
      containing the poly A tail. The molecular mass of the deduced amino acid (aa)
      sequence (189 aa) was 19.25 kDa long with an estimated pI of 8.39. It contains a
      putative selenocysteine residue which is encoded by the unusual stop codon, TGA,
      and forms the active site with residues Glu(75) and Trp(153). Comparison of amino
      acid sequences showed that white shrimp GPx is more closely related to GPx1 and
      GPx2 than to GPx3 and GPx4 of various animals. The GPx cDNA was synthesized in
      haemocytes, gills, the hepatopancreas, intestines, and muscles. The respiratory
      bursts of shrimp increased significantly after a Vibrio alginolyticus injection
      in order to kill the pathogen, and then induced increases in the activities of
      SOD and GPx to protect cells against damage from oxidation. However, GPx activity
      increased as a result of upregulated expression of GPx mRNA which was induced by
      the increase in H(2)O(2).

PMID- 17208012
TI  - Force output during fatigue with progressively increasing stimulation frequency.
AB  - There is currently a controversy over whether stimulation frequencies should
      increase or decrease to optimize force output over time. This study compared
      changes in thenar muscle force and M-wave amplitude during progressively
      increasing (20-40 Hz), decreasing (40-20 Hz) and constant (20 Hz) frequency
      stimulation of the median nerve continuously for 3 min. Twenty-three individuals
      participated in three sets of experiments. There was no significant difference in
      the force-time integrals between the three fatigue tasks. The rate of fatigue was
      not correlated to the number of stimulation pulses delivered (20 Hz: 3,600, 20-40
      and 40-20 Hz: 5,400). All fatigue tasks caused a significant reduction in M-wave
      amplitude and the reduction was largest for the 20-40 Hz protocol. However,
      multiple linear regression analysis revealed that the M-wave amplitude could not
      predict the changes in force over time for the 20 Hz or 20-40 Hz protocols. Thus
      during sustained evoked contractions with stimulation frequencies within the
      physiological range, frequencies can vary significantly without changing the
      overall force-time integral.

PMID- 17208013
TI  - Reproducibility of BOLD, perfusion, and CMRO2 measurements with calibrated-BOLD
      fMRI.
AB  - The coupling of changes in cerebral blood flow (CBF) and cerebral metabolic rate
      of oxygen (CMRO(2)) during brain activation can be characterized by an empirical
      index, n, defined as the ratio between fractional CBF change and fractional
      CMRO(2) change. The combination of blood oxygenation level dependent (BOLD)
      imaging with CBF measurements from arterial spin labeling (ASL) provides a
      potentially powerful experimental approach for measuring n, but the
      reproducibility of the technique previously has not been assessed. In this study,
      inter-subject variance and intra-subject reproducibility of the method were
      determined. Block design %BOLD and %CBF responses to visual stimulation and mild
      hypercapnia (5% CO(2)) were measured, and these data were used to compute the
      BOLD scaling factor M, %CMRO(2) change with activation, and the coupling index n.
      Reproducibility was determined for three approaches to defining regions-of
      interest (ROIs): 1) Visual area V1 determined from prior retinotopic maps, 2)
      BOLD-activated voxels from a separate functional localizer, and 3) CBF-activated
      voxels from a separate functional localizer. For estimates of %BOLD, %CMRO(2) and
      n, intra-subject reproducibility was found to be best for regions selected
      according to CBF activation. Among all fMRI measurements, estimates of n were the
      most robust and were substantially more stable within individual subjects
      (coefficient of variation, CV=7.4%) than across the subject pool (CV=36.9%). The
      stability of n across days, despite wider variability of CBF and CMRO(2)
      responses, suggests that the reproducibility of blood flow changes is limited by
      variation in the oxidative metabolic demand. We conclude that the calibrated BOLD
      approach provides a highly reproducible measurement of n that can serve as a
      useful quantitative probe of the coupling of blood flow and energy metabolism in
      the brain.

PMID- 17208014
TI  - Diffusion tensor imaging segmentation of white matter structures using a
      Reproducible Objective Quantification Scheme (ROQS).
AB  - Reproducible Objective Quantification Scheme (ROQS) is a novel method for
      regional white matter measurements of diffusion tensor imaging (DTI) parameters
      that overcomes the limitations of previous approaches for analyzing large cohorts
      of subjects reliably. ROQS is a semi-automated technique that exploits the fiber
      orientation information from the diffusion tensor in conjunction with a binary
      masking and chain-linking algorithm to segment anatomically distinct white matter
      tracts for subsequent quantitative analysis of DTI parameters such as fractional
      anisotropy and apparent diffusion coefficient. When applied to 3-T whole-brain
      DTI of normal adult volunteers, ROQS is shown to segment the corpus callosum much
      faster than manual region of interest (ROI) delineation, and with better
      reproducibility and accuracy.

PMID- 17208015
TI  - Duplication and paralog sorting of RPB2 and RPB1 genes in core eudicots.
AB  - RPB1 and RPB2, which encode the largest and second largest subunits of RNA
      polymerase II, respectively, are essential single copy genes in fungi, animals
      and most plants. Two paralogs of the RPB2 gene have been found in some groups of
      angioperms [Oxelman, B., Yoshikawa, N., McConaughy, B.L., Luo, J., Denton, A.L.,
      Hall, B.D., 2004. RPB2 gene phylogeny in flowering plants, with particular
      emphasis on asterids. Mol. Phylogenet. Evol. 32, 462-479]. Here, we report the
      results of experiments designed to identify the evolutionary origin of the RPB2
      duplicate copies. Through careful sampling and phylogenetic analysis, we were
      able to construct the RPB2 gene tree in angiosperms and infer the phylogenetic
      positions of the gene duplication and gene loss events that occurred. Our study
      shows that an RPB2 gene duplication occurred early in core eudicot evolution, at
      or near the time of the Buxaceae/Trochodendraceae divergence. Subsequently,
      multiple gene duplication and paralog sorting events happened independently in
      different core eudicot taxa. Differential expression of the two RPB2 gene
      paralogs may explain the preservation of both paralogs in the asterids. One gene
      (RPB2-i) accounts for most of the RPB2 mRNA made in the flower organs while the
      other gene (RPB2-d) is predominantly used in the vegetative tissues. We also
      found two paralogs of the RPB1 gene in some core eudicot species. The RPB1 gene
      duplication occurred before core eudicot divergence, around the time of RPB2 gene
      duplication. Several independent RPB1 paralog sorting events happened in
      different core eudicot taxa; their occurrence was independent of the RPB2 paralog
      sorting events. Our results suggest that a polyploidization event happened at or
      near the time of the Buxaceae/Trochodendraceae divergence. We propose that this
      polyploidization and the partial diploidization processes thereafter may have
      been the driving force of core eudicot radiation.

PMID- 17208016
TI  - Phylogenetic relationships among the Braconidae (Hymenoptera: Ichneumonoidea): a
      reassessment of Shi et al. (2005).

PMID- 17208017
TI  - Molecular phylogeny and evolutionary history of Southeast Asian macaques forming
      the M. silenus group.
AB  - The 12 presently recognized taxa forming the Macaca silenus group represent the
      most diverse lineage within the genus Macaca. The present study was set up to
      clarify the phylogenetic relationships of the extant members of the M. silenus
      group and to explain their geographical distribution patterns seen today. A
      combined approach involving the analysis of one paternal (TSPY) and two maternal
      (cyt b and 12S-16S rRNA) molecular markers enabled us to resolve the phylogenetic
      relationships within this lineage. Our Y chromosomal marker is not informative
      enough to allow detailed conclusion. Based on our mitochondrial data, however, M.
      pagensis, endemic to the three southern Mentawai islands (Sipora, North- and
      South Pagai), split off early (2.4-2.6 mya) and represents a sister clade to the
      macaques from the northern Mentawai island of Siberut and from those of the
      Southeast Asian mainland, which diverged in a radiation-like splitting event
      about 1.5-1.7 mya. By combining our new results with available data on
      behavioural as well as climate and sea level changes in Southeast Asia during the
      Plio- and Pleistocene, we have developed two scenarios for the evolutionary
      history of this primate group, which may help explain the current geographical
      distribution of its members.

PMID- 17208018
TI  - A comprehensive DNA sequence library is essential for identification with DNA
      barcodes.
AB  - In this study we examine the possibility of utilising partial cox1 gene sequences
      as barcodes to identify non-biting midges (Diptera: Chironomidae). We analysed
      DNA from 97 specimens of 47 species in the genera Cladotanytarsus, Micropsectra,
      Parapsectra, Paratanytarsus, Rheotanytarsus, Tanytarsus and Virgatanytarsus with
      a main focus on Micropsectra, Parapsectra and Paratanytarsus. Our findings show
      that (1) cox1 is easily amplified from extracts from different life stages with
      the standard barcoding primers. (2) Although K2P-distances between con-specific
      sequences varied up to 4.9%, con-specifics clustered together with 91-100%
      bootstrap support in maximum parsimony analysis. This indicates that barcodes may
      be excellent tools to identify species that are already in a cox1 library. (3)
      Both neighbour joining and maximum parsimony failed to reconstruct monophyletic
      genera. Thus, if a well-matching cox1 sequence is not already available in the
      library, the prospects of approximately identifying an unknown taxon, even to the
      correct genus of subtribe Tanytarsina, are not good.

PMID- 17208019
TI  - Phylogenetics of the woodrat genus Neotoma (Rodentia: Muridae): implications for
      the evolution of phenotypic variation in male external genitalia.
AB  - Interspecific morphological variation in animal genitalia has long attracted the
      attention of evolutionary biologists because of the role genital form may play in
      the generation and/or maintenance of species boundaries. Here we examine the
      origin and evolution of genital variation in rodents of the muroid genus Neotoma.
      We test the hypothesis that a relatively rare genital form has evolved only once
      in Neotoma. We use four mitochondrial and four nuclear markers to evaluate this
      hypothesis by establishing a phylogenetic framework in which to examine genital
      evolution. We find intron seven of the beta-fibrinogen gene to be a highly
      informative nuclear marker for the levels of differentiation that characterize
      Neotoma with this locus evolving at a rate slower than cytochrome b but faster
      than 12S. We estimate phylogenetic relationships within Neotoma using both
      maximum parsimony and maximum likelihood-based Bayesian methods. Our Bayesian and
      parsimony reconstructions differ in significant ways, but we show that our
      parsimony analysis may be influenced by long-branch attraction. Furthermore, our
      estimate of Neotoma phylogeny remains consistent across various data partitioning
      strategies in the Bayesian analyses. Using ancestral state reconstruction, we
      find support for the monophyly of taxa that possess the relatively rare genital
      form. However, we also find support for the independent evolution of the common
      genital form and discuss possible underlying developmental shifts that may have
      contributed to our observed patterns of morphological evolution.

PMID- 17208020
TI  - Chromatin supraorganization, DNA fragmentation, and cell death in erythrocytes of
      the rattlesnake, Crotalus durissus terrificus (Serpentes, Viperidae), infected
      with the protozoan, Hepatozoon spp. (Apicomplexa, Hepatozoidae).
AB  - Forms of the protozoan of the Hepatozoon genus are detected free in the
      circulation and also within some of the erythrocytes of infected snakes. In
      healthy snakes, DNA fragmentation and cell death usually affect a few circulating
      erythrocytes in agreement with the long life span expected for these cells. In
      the present study we investigated whether infection by Hepatozoon spp. affected
      the incidence of DNA fragmentation and cell death in erythrocytes from the
      rattlesnake, Crotalus durissus terrificus. Methods such as the kinetics of
      Feulgen-DNA hydrolysis, and the TUNEL and comet assays, previously used for the
      study of chromatin organization and DNA fragmentation in erythrocytes of healthy
      snakes, were used. The results indicated that Hepatozoon spp. increased the DNA
      fragmentation and chromatin condensation typical of cell death in circulating
      erythrocytes of C. d. terrificus, including cells that do not harbour the
      parasite. The Hepatozoon infection is thus suggested to accelerate destruction of
      erythrocytes in the rattlesnake, not only affecting cells harbouring the
      parasite, but also in those without it.

PMID- 17208021
TI  - Synergistic effects of pravastatin and pioglitazone in renal tubular epithelial
      cells induced by transforming growth factor-beta1.
AB  - Recent studies suggest that treatment with PPAR-gamma agonists and statins have
      beneficial effects on renal disease. However, the combined effects of PPAR-gamma
      agonists and statins in human renal epithelial cells are unknown. Our present
      study revealed that there were synergistic effects of pravastatin and
      pioglitazone in the expression of alpha-smooth muscle actin (alpha-SMA),
      connective tissue growth factor (CTGF), fibronectin (FN), plasminogen activator
      inhibitor-1 (PAI-1) and collagen 1 in human renal proximal tubular epithelial
      cells induced by transforming growth factor-beta 1 (TGF-beta1). The beneficial
      effects of combined therapy against renal tubular epithelial cell injury are
      attributed, at least in part, to the inhibition of transdifferentiation,
      extracellular matrix deposition and cytokine production.

PMID- 17208023
TI  - Density functional theory study of the inner hydrogen atom transfer in metal-free
      porphyrins: meso-substitutional effects.
AB  - Density functional theory (DFT) calculations were carried out to study the
      influence of both electron-withdrawing fluorine and electron-donating amidogen
      meso-substituents on the inner hydrogen transfer in metal-free porphyrins. Twenty
      four stable structures and 21 transition states among the stable structures are
      fully optimized at the B3LYP/6-31G (d) level, and vibration analyses are carried
      out to verify the optimized structures. It is found that the acidity of the
      transferred hydrogen atom, the basicity of the nitrogen atoms of the adjacent
      pyrrole ring, the distance from the transferred hydrogen atom to the nitrogen
      atom of the adjacent pyrrole ring, and the electronic nature of meso-substituents
      in transfer paths, all have significant influences on the potential energy
      barrier of the inner hydrogen transfer in porphyrins. The different transfer
      paths of each substituted porphyrin are compared, all the transfer barriers are
      compared to unsubstituted metal free porphyrin, and the infrared and electronic
      absorption spectra of some important complexes are described. By placing
      substituents appropriately, the cis-trans transition energy barrier can be
      greatly decreased, and the cis-porphyrin conformer which can be detected
      spectroscopically may be significantly stabilized. The present work would shed
      light on tuning the transition barrier by selecting the most appropriate paths
      and detecting cis-porphyrins experimentally.

PMID- 17208022
TI  - Zoonotic bacterial populations, gut fermentation characteristics and methane
      production in feedlot steers during oral nitroethane treatment and after the
      feeding of an experimental chlorate product.
AB  - Nitroethane inhibits the growth of certain zoonotic pathogens such as
      Campylobacter and Salmonella spp., foodborne pathogens estimated to cause
      millions of human infections each year, and enhances the Salmonella- and
      Escherichia coli-killing effect of an experimental chlorate product being
      developed as a feed additive to kill these bacteria immediately pre-harvest.
      Limited studies have shown that nitroethane inhibits ruminal methane production,
      which represents a loss of 2-12% of the host's gross energy intake and
      contributes to global warming and destruction of the ozone layer. The present
      study was conducted to assess the effects of 14-day oral nitroethane
      administration, 0 (0X), 80 (1X) or 160 (2X)mg nitroethane/kg body weight per day
      on ruminal and fecal E. coli and Campylobacter, ruminal and fecal methane
      producing and nitroethane-reducing activity, whole animal methane emissions, and
      ruminal and fecal fermentation balance in Holstein steers (n=6 per treatment)
      averaging 403+/-26 (SD) kg BW. An experimental chlorate product was fed the day
      following the last nitroethane administration to determine effects on E. coli and
      Campylobacter. The experimental chlorate product decreased (P<0.001) fecal, but
      not ruminal (P>0.05) E. coli concentrations by 1000- and 10-fold by 24 and 48 h,
      respectively, after chlorate feeding when compared to pre-treatment
      concentrations (>5.7 log(10) colony forming units/g). No effects (P>0.05) of
      nitroethane or the experimental chlorate product were observed on fecal
      Campylobacter concentrations; Campylobacter were not recovered from ruminal
      contents. Nitroethane treatment decreased (P<0.01) ruminal (8.46, 7.91 and 4.74+/
      0.78 micromol/g/h) and fecal (3.90, 1.36 and 1.38+/-0.50 micromol/g/h) methane
      producing activity for treatments 0X, 1X and 2X, respectively. Administration of
      nitroethane increased (P<0.001) nitroethane-reducing activity in ruminal, but not
      fecal samples. Day of study affected ruminal (P<0.0001) but not fecal (P>0.05)
      methane-producing and nitroethane-reducing activities (P<0.01); treatment by day
      interactions were not observed (P>0.05). Ruminal accumulations of acetate
      decreased (P<0.05) in 2X-treated steers when compared with 0X- and 1X-treated
      steers, but no effect (P>0.05) of nitroethane was observed on propionate,
      butyrate or the acetate to propionate ratio. Whole animal methane emissions,
      expressed as L/day or as a proportion of gross energy intake (%GEI), were
      unaffected by nitroethane treatment (P>0.05), and were not correlated (P>0.05)
      with ruminal methane-producing activity. These results demonstrate that oral
      nitroethane administration reduces ruminal methane-producing activity but suggest
      that a microbial adaptation, likely due to an in situ enrichment of ruminal
      nitroethane-reducing bacteria, may cause depletion of nitroethane, at least at
      the 1X administration dose, to concentrations too low to be effective. Further
      research is warranted to determine if the optimization of dosage of nitroethane
      or related nitrocompouds can maintain the enteropathogen control and anti
      methanogen effect in fed steers.

PMID- 17208024
TI  - QSAR study of a large set of 3-pyridyl ethers as ligands of the alpha4beta2
      nicotinic acetylcholine receptor.
AB  - Extensive 3D-QSAR studies were performed on 158 diverse analogues of 3-pyridyl
      ethers, which are excellent ligands of alpha4beta2 neuronal nicotinic
      acetylcholine receptor (NnAChR). Comparative molecular field analysis (CoMFA) and
      comparative molecular similarity indices analysis (CoMSIA) techniques were used
      to relate the binding affinities with the ligand structures. Two QSAR models were
      obtained using CoMFA and CoMSIA techniques. The two QSAR models were proved to be
      statistically significant and have high predictive power. The best CoMFA model
      yielded the cross-validated q(2)=0.605 and the non-cross-validated r(2)=0.862.
      The derived model indicated the importance of steric (85.9%) as well as
      electrostatic (14.1%) contributions. The CoMFA model demonstrated the steric
      field as the major descriptor of the ligand binding. The best CoMSIA model gave
      q(2)=0.723 and r(2)=0.685. This model showed that steric (30.3%) and H-bond
      interaction (61.8%) properties played major roles in ligand binding process. The
      squares of correlation coefficient for external test set of 28 molecules were
      0.723 and 0.685 for the CoMFA model and the CoMSIA model, respectively. The two
      models were further graphically interpreted in terms of field contribution maps.
      SAR studies were also performed on different series of compounds in order to get
      a more reasonable understanding of the interactions between the ligands and the
      receptor. With the results, we have also presumed some assistant elements as
      supplements to the traditional pharmacophoric elements. A crude vision of ligand
      localization in the ligand-binding pocket of the receptor was also obtained,
      which would favor for the docking study of this kind of ligands.

PMID- 17208025
TI  - The putative mechanism of Na(+) absorption in euryhaline elasmobranchs exists in
      the gills of a stenohaline marine elasmobranch, Squalus acanthias.
AB  - We recently cloned an NHE3 orthologue from the gills of the euryhaline Atlantic
      stingray (Dasyatis sabina), and generated a stingray NHE3 antibody to
      unequivocally localize the exchanger to the apical side of epithelial cells that
      are rich with Na(+)/K(+)-ATPase (A MRC). We also demonstrated an increase in NHE3
      expression when stingrays are in fresh water, suggesting that NHE3 is responsible
      for active Na(+) absorption. However, the vast majority of elasmobranchs are only
      found in marine environments. In the current study, immunohistochemistry with the
      stingray NHE3 antibody was used to localize the exchanger in the gills of the
      stenohaline marine spiny dogfish shark (Squalus acanthias). NHE3 immunoreactivity
      was confined to the apical side of cells with basolateral Na(+)/K(+)-ATPase and
      was excluded from cells with high levels of vacuolar H(+)-ATPase. Western blots
      detected a single protein of 88 kDa in dogfish gills, the same size as NHE3 in
      stingrays and mammals. These immunological data demonstrate that the putative
      cell type responsible for active Na(+) absorption in euryhaline elasmobranchs is
      also present in stenohaline marine elasmobranchs, and suggest that the inability
      of most elasmobranchs to survive in fresh water is not due to a lack of the gill
      ion transporters for Na(+) absorption.

PMID- 17208026
TI  - Adrenergic receptor density in brown adipose tissue of active and hibernating
      hamsters and ground squirrels.
AB  - The ligand-binding characteristics (B(max) and K(D)) of alpha(1)- and
      beta(1)/beta(2)-adrenoceptors were investigated in membranes prepared from brown
      adipose tissue (BAT) of warm-acclimated, cold-acclimated, hibernating and
      arousing ground squirrels (Spermophillus undulatus) and hamsters (Mesocricetus
      auratus) by specific binding of [(3)H]prazosin and [(3)H]CGP-12177, respectively.
      The physiological state did not change the affinity for the adrenoceptors in the
      BAT of ground squirrels and hamsters. There was a significant decrease in
      alpha(1)-receptor density in arousing ground squirrels and a significant decrease
      in beta(1)/beta(2) density in hibernating ground squirrels. The level of alpha(1)
      receptors was in all conditions higher than that of beta(1)/beta(2) receptors.
      The results indicate a possible change in balance of adrenoceptor density in the
      processes of cold acclimation, hibernation and arousal. The balance between the
      various adrenoceptor subtypes may be important for the final effect of
      catecholamines in BAT in different physiological states.

PMID- 17208027
TI  - Post-eclosion decline in 'knock-down' thermal resistance and reduced effect of
      heat hardening in Drosophila melanogaster.
AB  - The dependency of knock-down resistance on age, from 0 to 12 days post eclosion,
      was studied in two lines of Drosophila melanogaster, one selected for knock-down
      resistance and one unselected control. Additionally, the inducible Hsp70
      expression level was assessed at maintenance temperature and after a heat
      hardening treatment (1 h at 35 degrees C) at the same ages. Knock-down resistance
      decreased roughly linearly with age in both control and knock-down selected lines
      and in both sexes regardless of maintenance temperature. Hsp70 expression,
      however, fell only from day 0 to day 3 and was thereafter changed little.
      Acclimation did not result in detectable difference between lines. The effect of
      hardening was only significant for control flies. This suggests that the
      increased knock-down resistance of the selected line was reached at the expense
      of hardening ability.

PMID- 17208028
TI  - Dietary thyroxine induces molt in chickens (Gallus gallus domesticus).
AB  - Thyroxine increases during a molt in wild and captive birds, and thyroidectomy
      prevents induction of molt. This trial examined the effect of dietary thyroxine
      on molt induction molt in chickens (laying hens, 59 weeks of age). In a
      completely randomized design (n=15 hens/replication; 6 replications/treatment),
      hens were randomly assigned to either a traditional molting program consisting of
      feed withdrawal (FWD), or to diets containing 40 mg thyroxine/kg diet (HT), 20 mg
      thyroxine/kg diet (LT), or 40 mg thyroxine from thyroactive iodinated casein/kg
      diet (TIC). The molting treatment lasted 7-13 d, until egg production reached 0%.
      After molt induction, birds had ad libitum access to the same diet, until egg
      production was re-initiated and maximized ( approximately 56 d). All treatments
      induced molt, based upon cessation of egg laying and regression of ovary and
      oviduct. Birds on FWD treatment lost more body weight during the molting period,
      but gained more after molt compared to thyroxine treatments (P<0.01 for each),
      although all body weights were similar when egg production was maximized. Data
      demonstrate that oral thyroxine, in purified or non-purified form, induces a molt
      and may enhance animal well-being by reducing the need for FWD.

PMID- 17208029
TI  - Food digestion by cathepsin L and digestion-related rapid cell differentiation in
      shrimp hepatopancreas.
AB  - Cathepsin L (CatL) has been readily localized in the large vacuole and in the
      apical complex of the digestive B-cell of the shrimp hepatopancreas. Immunogold
      technique revealed the occurrence of CatL in zymogen granule, digestive body and
      digestive vacuole of the B-cell in the hepatopancreas of Metapenaeus ensis.
      Coalescences of zymogen granule with sub-apical vacuole, and of two small
      digestive bodies were observed. This progressive coalescence of CatL vesicles is
      direct evidence of involvement of CatL in intracellular digestion. Released CatL
      vesicles and free CatL were found in the lumen of hepatopancreatic tubule. CatL
      mRNA existed in F-cell, but not in the mature B-cell. This finding supports the
      previous suggestion that F-cell is the precursor of B-cell. F-cell is a transient
      form. Transition from F-cell to B-cell is fast. We define F-cell as the
      transcribing cell, F/B-cell as the enzyme-synthesizing cell and B-cell as the
      enzyme-secreting cell. For the first time, we suggest that R-cell is the
      replacing cell for the leaving B-cell. CatL degrades nutrient intracellularly and
      extracellularly. The most interesting finding is that CatL is transcribed in one
      type of cell, and the very cell evolves quickly to a morphologically different
      cell where the enzyme functions.

PMID- 17208030
TI  - Prevalence of Coxiella burnetii DNA in vaginal and uterine samples from healthy
      cats of north-central Colorado.
AB  - Q fever is a worldwide zoonotic disease caused by Coxiella burnetii. Although
      traditionally associated with livestock exposure, human infection has also been
      documented from contact with parturient cats. The goal of this study was to
      determine the prevalence of C burnetii DNA in uterine and vaginal tissues from
      healthy client-owned and shelter cats of north-central Colorado using polymerase
      chain reaction assay. Coxiella burnetii was not amplified from vaginal samples of
      any cat or uterine biopsies of shelter cats. However, a nucleotide sequence with
      99% homology to C burnetii DNA was amplified from four of 47 (8.5%) uterine
      biopsies of client-owned cats. This study demonstrates that clinically normal
      cats in north-central Colorado can harbor C burnetii. Care should be taken when
      attending to parturient cats and contact with parturient secretions should be
      avoided. Additional studies are indicated to further characterize the role of
      cats in zoonotic Q fever.

PMID- 17208031
TI  - [Chemoradiation for locally advanced non-small cell lung cancer].
AB  - Chemoradiation is one of the major therapeutic options in thoracic oncology:
      besides surgery, the best treatment for early-stage tumors, and chemotherapy, not
      only used in metastatic tumors, but also in a neoadjuvant and adjuvant setting,
      chemoradiation is the standard strategy for unresectable locally advanced non
      small cell lung cancer. Its current modalities include three-dimensional
      conformal techniques, allowing dose escalation and sequential and concurrent
      combination with new generation cytotoxic agents to occur. Phase III trials are
      currently evaluating the benefit from induction and consolidation chemotherapy in
      this setting. New techniques of radiation may also increase the efficacy and the
      feasibility of radiation. This constant progress makes chemoradiation one of the
      most promising combined treatments in thoracic oncology.

PMID- 17208032
TI  - Shiga toxin binding in normal and inflamed human intestinal mucosa.
AB  - Shiga toxins are associated with haemolytic uraemic syndrome but human intestinal
      epithelium does not express the Gb3 receptor. We describe Gb3 expression and
      Shiga toxin binding in histologically normal intestine and demonstrate that the
      pattern is unaltered in inflammatory disease states. Gb3 expression and Shiga
      toxin binding were identified in Paneth cells in both normal and inflamed
      mucosae.

PMID- 17208033
TI  - The need for the "new health geography" in epidemiologic studies of environment
      and health.
AB  - Growth during the past decade in what can be broadly referred to as social and
      environmental epidemiologic research has been an important contributor to an
      emerging understanding of environment and health relationships. While the
      incorporation of geographic information systems as well as concepts such as
      "neighborhoods" might be viewed as evidence of social epidemiology moving closer
      to health geography, I argue that the two fields are not well aligned. Health
      geography has much more to contribute to studies of environment and health, and
      attention by social epidemiologists to those potential contributions could help
      rectify this misalignment. This paper suggests a number of geographic
      perspectives on health and environment that could create useful connections
      between geography and public health, via social epidemiology. To illustrate this
      potential, I use an ongoing study of a Texas community exposed to a large
      petrochemical complex-an inquiry constructed in the mode of social epidemiology -
      as a case in point. I apply several perspectives and concepts from geography to
      the case study. Cultural ecology, discourse materialized, political ecology, and
      territoriality are used to assess the Texas City situation and suggest important
      types of understandings that can enhance the social epidemiology approach to
      environment and health. I conclude with a discussion of the prospects for a
      social epidemiology infused with this type of geographic thought and analysis.

PMID- 17208034
TI  - Postpartum characteristics of rectus abdominis on ultrasound imaging.
AB  - This cross-sectional and partial longitudinal study aimed to characterize changes
      in rectus abdominis (RA) and provide reference ranges for the first year
      postpartum. Ultrasound scanning was used at four stages postnatally to measure
      cross-sectional area (CSA), thickness, width (indirectly using a shape value) and
      inter-recti distance (IRD). One hundred and fifteen postnatal women (though some
      postnatal subjects appeared in more than one postnatal group thus giving a total
      of 183 data points) and 69 age-matched nulliparous female controls were
      recruited. Postnatal subjects were studied at Day 1 (PN1; n=63) and at 2 (PN2;
      n=55), 6 (PN3; n=39) and 12 (PN4; n=26) months postpartum. Longitudinal data were
      analysed for CSA, thickness, shape (indirect width measurement) (df=67) and IRD
      (df=62). The mean CSA of the PN1 group was significantly larger (P<0.001) than in
      controls and decreased (P<0.0021) by 12 months. In all postnatal groups, RA was
      significantly thinner (P<0.0001, PN1-PN3; P<0.0478, PN4), wider (P<0.0001, PN1
      PN3; P=0.0326, PN4) and the IRD was significantly larger (P<0.0001, PN1-PN4) than
      in controls. Over 2 months postpartum, RA became thicker (P=0.0003) and the width
      and IRD decreased (P<0.0001 and P=0.0002, respectively) but did not return to
      control values by 12 months. These results have implications for strength of RA
      postpartum and anterior abdominal wall stiffness, which together with other
      muscle characteristics could inform development of effective postnatal exercise
      programmes.

PMID- 17208035
TI  - Ontology annotation: mapping genomic regions to biological function.
AB  - With numerous whole genomes now in hand, and experimental data about genes and
      biological pathways on the increase, a systems approach to biological research is
      becoming essential. Ontologies provide a formal representation of knowledge that
      is amenable to computational as well as human analysis, an obvious underpinning
      of systems biology. Mapping function to gene products in the genome consists of
      two, somewhat intertwined enterprises: ontology building and ontology annotation.
      Ontology building is the formal representation of a domain of knowledge; ontology
      annotation is association of specific genomic regions (which we refer to simply
      as 'genes', including genes and their regulatory elements and products such as
      proteins and functional RNAs) to parts of the ontology. We consider two
      complementary representations of gene function: the Gene Ontology (GO) and
      pathway ontologies. GO represents function from the gene's eye view, in relation
      to a large and growing context of biological knowledge at all levels. Pathway
      ontologies represent function from the point of view of biochemical reactions and
      interactions, which are ordered into networks and causal cascades. The more
      mature GO provides an example of ontology annotation: how conclusions from the
      scientific literature and from evolutionary relationships are converted into
      formal statements about gene function. Annotations are made using a variety of
      different types of evidence, which can be used to estimate the relative
      reliability of different annotations.

PMID- 17208036
TI  - Small molecule approaches in plants.
AB  - Small molecules offer exciting opportunities for plant science. So far, bioactive
      small molecules have been identified as plant hormones, herbicides, growth
      regulators, or taken from animal research. Recently, plant scientists have
      started to explore further the chemical space for novel modulators of plant
      hormone signalling, and have followed up this work with exciting discoveries
      illustrating the potential of small molecules such as brassinazole and sirtinol.
      New chemical genetic screens have been designed to generate chemical tools for
      the investigation of membrane trafficking, gravitropism and plant immunity.
      Further novel 'chemetic' tools to identify targets and modes of action are
      currently generated through an intimate interdisciplinary collaboration between
      biologists and small molecule chemists.

PMID- 17208037
TI  - Probing glycomics.
AB  - The study of protein-carbohydrate interactions is one central theme of glycomics
      research. The challenges encountered when investigating these interactions have
      resulted in an approach that studies saccharides through the enzymes that process
      them. Proteins and their function are often probed by manipulating the genes that
      encode them. Efforts in proteoglycomics exploring protein-binding properties and
      the enzymatic modification of carbohydrates have intensified, and synthetic
      tools, including activity- and affinity-based probes, have enhanced our
      understanding of the roles of carbohydrates in biology.

PMID- 17208038
TI  - Adaptation to the host environment: regulation of the SPI1 type III secretion
      system in Salmonella enterica serovar Typhimurium.
AB  - Salmonella enterica invades the intestinal epithelium of the host using a type
      III secretion system encoded on Salmonella pathogenicity island 1 (SPI1). The
      bacteria integrate environmental signals from a variety of global regulatory
      systems to precisely induce transcription of SPI1. The regulatory circuit
      converges on expression of HilA, which directly regulates transcription of the
      SPI1 apparatus genes. Transcription of hilA is controlled by a complex feed
      forward loop. Regulatory signals feed into the system through post
      transcriptional and post-translational control of HilD, which in turn activates
      HilC and RtsA. These three regulators act in concert to control hilA
      transcription. The system acts as a switch, ensuring that SPI1 is fully on at the
      appropriate time.

PMID- 17208039
TI  - Chlamydial interferon gamma immune evasion influences infection tropism.
AB  - Chlamydia trachomatis is a human pathogen and Chlamydia muridarum is a mouse
      pathogen but paradoxically, they share near genomic synteny. The majority of
      strain-variable genes are located primarily in a hyper-variable region termed the
      plasticity zone. Tryptophan synthase and cytotoxin are plasticity zone genes
      unique to the human and murine strains, respectively. Tryptophan synthase is a
      virulence factor that differentiates C. trachomatis strains into genital and
      ocular disease pathotypes, whereas cytotoxin(s) is a virulence factor linked to
      murine infection tropism. Divergence in these loci is strongly correlated with
      host-specific interferon gamma effector activities, suggesting that these
      virulence genes have co-evolved with their respective hosts as a primary
      mechanism to evade innate immunity. These findings have important implications
      for chlamydial animal modeling studies.

PMID- 17208040
TI  - The quality of evidence in health informatics: how did the quality of healthcare
      IT evaluation publications develop from 1982 to 2005?
AB  - OBJECTIVE: To obtain an overview of study designs and study methods used in
      research evaluating IT in health care, to present a list of quality criteria by
      which all kinds of reported evaluation studies on IT systems in health care can
      be assessed, and to assess the quality of reported evaluation studies on IT in
      health care and its development over time (1982-2005). METHODS: A generic 10-item
      list of quality indicators was developed based on existing literature on quality
      of medical and medical informatics publications. It is applicable to all kind of
      IT evaluation papers and not restricted to randomized controlled trials. One
      hundred and twenty explanatory papers evaluating the effects of an IT system in
      health care published between 1982 and 2005 were randomly selected from PubMed,
      the study designs and study methods were extracted, and the quality indicators
      were used to assess the quality of each paper by two independent raters. RESULTS:
      The inter-rater variability of scoring the 10 quality indicators as assessed by a
      pre-test with nine papers was good (K=0.87). There was a trend towards more multi
      centre studies and authors coming more frequently from various departments. About
      70% of the studies used a design other than a randomized controlled trial (RCT).
      Forty percent of the studies combined at least two different data acquisition
      methods. The quality of IT evaluation papers, as defined by the quality
      indicators, was only slightly improving in time (Spearman correlation coefficient
      [rs]=0.19). The quality of RCTs publications was significantly higher than the
      quality of non-RCT studies (p<0.001). CONCLUSION: The continuous and dominant
      number of non-RCT studies reflects the various approaches applicable to evaluate
      IT systems in health care. Despite the increasing discussion on evidence-based
      health informatics, the quality of published evaluation studies on IT
      interventions in health care is still insufficient in some aspects. Journal
      editors and referees should take care that reports of evaluation on IT systems
      contain all aspects needed for a sufficient understanding and reproducibility of
      a paper. Publication guidelines should be developed to support more complete and
      better publications of IT evaluation papers.

PMID- 17208041
TI  - The role of perceptions of clinicians in their adoption of a web-based antibiotic
      approval system: do perceptions translate into actions?
AB  - PURPOSE: Computerized Decision Support Systems have been shown to improve
      clinicians' performance. Clinicians' adoption of these systems is crucial for
      their success. Studying clinicians' perceptions can provide an insight into the
      determinants of clinicians' adoption of such systems. The aim of this study was
      to measure clinicians' perceptions of ease of use and usefulness of a web-based
      antibiotic approval system, and to investigate the relationship between the
      reported perceptions and use of the system. METHODS: Potentially identifiable
      coded surveys were sent to a total of 70 senior and 150 junior medical staff, and
      30 pharmacists all working at a tertiary care referral teaching hospital of
      Melbourne, Australia. Clinicians' perceptions of ease of use and usefulness of
      the antibiotic approval system; clinicians' general computer use; and clinicians'
      usage of the antibiotic approval system were measured. RESULTS: The overall
      response rate from the clinicians was 53.4%. The majority of the participants
      (70% and above) found it easy to obtain antibiotic approval using the system.
      More than 80% of the participants believed that the system will decrease the
      inappropriate use of antibiotics at the hospital. Clinicians who were more likely
      to use the system also found it easy to learn (Rho=0.392, p=0.001), easy to show
      others how to use the system (Rho=0.298, p=0.014), easy to find additional
      information (Rho=0.317, p=0.009), and easy to use it within their daily workflow
      (Rho=0.268, p=0.028). In addition, the clinicians were also more likely to use
      the system if they believed that it will improve their adherence to evidence
      based practice (Rho=0.352, p=0.003). CONCLUSION: The majority of clinicians in an
      independent investigation of the antibiotic approval system found the system easy
      to use and useful to them. A number of clinicians' perceptions about the system
      were found to be correlated with the actual usage of the system by the
      clinicians.

PMID- 17208042
TI  - The use of drug resistance algorithms and genotypic inhibitory quotient in
      prediction of lopinavir-ritonavir treatment response in human immunodeficiency
      virus type 1 protease inhibitor-experienced patients.
AB  - BACKGROUND: Different approaches using genotypic, pharmacokinetic parameters or
      combination of both have been recently developed to monitor antiretroviral
      treatment in HIV-1-infected individuals. Their uses in clinical practice may
      improve the benefit of protease inhibitor-based salvage therapy while reducing
      treatment toxicity and emergence of viral resistance. OBJECTIVES: To assess the
      prediction of genotypic inhibitory quotient (GIQ) using different genotypic drug
      resistance interpretation's algorithms and lopinavir plasma concentration in PI
      experienced patients treated by lopinavir/ritonavir (LPV/r). Genotypic
      susceptibility score (GSS) was also evaluated. STUDY DESIGN: Forty-seven HIV-1 PI
      experienced, but LPV naive patients were included in a retrospective cohort
      study. Plasma HIV-1 viral load (VL), CD4 cell count and LPV plasma concentrations
      were assessed at weeks (W) 12 and 24. Interpretation of baseline resistance
      genotype was achieved according to four different algorithms and GSS calculated
      using two expert systems. GIQ was defined as the ratio of LPV concentration to
      the number of LPV resistance mutations at day 0 (D0) and patients classified by
      units of GIQ. The end point of the study was the virological response expressed
      in HIV VL median decrease from D0 to W24. RESULTS: The overall median VL decrease
      from D0 to W24 was -2.42 log(10)copies/mL and 60% of patients had VL below 400
      copies/mL. The LPV mutation score was predictive of response for all algorithms
      whereas plasma concentrations of LPV were not. Mean VL decrease was greater for
      higher GIQ classes and difference reached statistical significance at W24. When
      considering virological response at W24, GSS calculated with ANRS and Stanford
      system were good predictor scores as areas under the receiver operating
      characteristics (ROC) curves were 0.76 for both. CONCLUSION: GIQ was found to be
      a useful drug-monitoring tool which could be helpful in targeting LPV
      concentrations in order to achieve long-term undetectable viral load,
      particularly in genotypic resistant patients.

PMID- 17208043
TI  - Secretion and lysophospholipase D activity of autotaxin by adipocytes are
      controlled by N-glycosylation and signal peptidase.
AB  - Autotaxin (ATX) is a lysophospholipase D involved in synthesis of
      lysophosphatidic acid (LPA). ATX is secreted by adipocytes and is associated with
      adipogenesis and obesity-associated diabetes. Here we have studied the mechanisms
      involved in biosynthesis and secretion of ATX by mouse 3T3-F442A adipocytes. We
      found that inhibition of N-glycosylation with tunicamycin or by double point
      deletion of the amino-acids N53 and N410 of ATX inhibit its secretion. In
      addition, N-glycosidase treatment and point deletion of the amino-acid N410
      inhibits the lysophospholipase D activity of ATX. Analysis of the amino-acid
      sequence of mouse ATX shows the presence of a N-terminal signal peptide.
      Treatment with the signal peptidase inhibitor globomycin inhibits ATX secretion
      by adipocytes. Transfection in Cos-7 cells of site-directed deleted ATX shows
      that ATX secretion is dependent on the hydrophobic core sequence of the signal
      peptide, not on the putative signal peptidase cleavage site sequence. Analysis of
      the amino-acid sequence of mouse ATX also reveals the presence of a putative
      cleavage site by the protein convertase furin. Treatment of adipocytes with the
      furin inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethylketone does not modified
      secretion or lysophospholipase D activity of ATX. Transfection in Cos-7 cells of
      site-directed deleted ATX shows that the furin recognition site is not required
      for secretion or lysophospholipase D activity of ATX. In conclusion, the present
      work demonstrates the crucial role of N-glycosylation in secretion and activity
      of ATX. The present work also confirms the crucial role signal peptidase in
      secretion of ATX by adipocytes.

PMID- 17208044
TI  - Effects of ageing on cognitive task preparation as reflected by event-related
      potentials.
AB  - OBJECTIVE: The anticipation of complex cognitive tasks involves effortful
      preparation being reflected in the contingent negative variation (CNV) of the
      event-related potential. In the literature there are contradictory results
      concerning the effect of age on this potential. We wanted to investigate effects
      of age, time-on-task, and task difficulty on the CNV. METHOD: Young and middle
      aged participants performed a visual search and a non-search task during an early
      and a late phase of a 6-h session. RESULTS: Performance data revealed increased
      response times and error rates for middle-aged vs. young participants. Most
      importantly, an increased frontal CNV amplitude was found for the older
      participants, especially pronounced in the search task. A late positivity which
      was elicited to the offset of the preceding stimulus was increased for the middle
      aged vs. young group in the visual search task only. There was no effect of time
      on-task on performance, but the CNV became larger with time-on-task in the search
      task while it became smaller in the non-search task. CONCLUSIONS: The results
      suggest an enhancement of effortful task preparation for middle-aged participants
      especially when the task is difficult. SIGNIFICANCE: This underlines the role of
      the CNV as a neurophysiological indicator for effortful cognitive preparation.

PMID- 17208045
TI  - Is the P300 deficit in alcoholism associated with early visual impairments (P100,
      N170)? An oddball paradigm.
AB  - OBJECTIVE: Studies exploring chronic alcoholism with event-related potentials
      (ERPs) have shown delayed latency and reduced amplitude of the P300, a long
      lasting positive potential reflecting decisional processing. This P300 deficit in
      alcoholism is generally interpreted as a disturbance in central nervous system
      inhibition or in memory/attention. The present study aimed at identifying if this
      electrophysiological deficit is already present on earlier components, and
      advances a new hypothesis concerning the interpretation of the P300 alteration.
      METHODS: Patients suffering from alcoholism and matched healthy controls had to
      detect, in an oddball paradigm, emotional faces among a succession of neutral
      faces. Behavioral performance and ERP data (recorded from 32 electrodes) were
      analyzed. RESULTS: In line with previous studies, data showed that alcoholism led
      to a P300 deficit. Moreover, we observed for the first time that this deficit
      begins at earlier visual (P100) and face-processing (N170) stages, and we found
      high positive correlations between P100, N170 and P300 for amplitude and latency
      values, suggesting cumulative deficits on the cognitive continuum. CONCLUSIONS:
      We suggest that the P300 deficit observed in chronic alcoholism could be linked
      to earlier visuo-spatial deficits rather than being an impairment of the specific
      processes linked to the P300. SIGNIFICANCE: These results call for reconsidering
      the interpretation of P300 impairments at a fundamental and clinical level, and
      shows that earlier ERP components must be taken into account in future studies.

PMID- 17208046
TI  - Event-related potentials in idiopathic rapid eye movements sleep behaviour
      disorder.
AB  - OBJECTIVE: To assess psychophysiological parameters in idiopathic rapid eye
      movements sleep behaviour disorder (RBD), in order to identify possible markers
      for pre or sub-clinical cognitive abnormalities. METHODS: Sixteen consecutive
      unmedicated patients with idiopathic RBD and 16 age- and sex-matched controls
      performed active and passive auditory oddball paradigms and an attentional test.
      RESULTS: There were no significant between-group latency and amplitude
      differences. The two groups showed a difference in the inter-peak interval
      between N100 and P200 in the active condition. A significant correlation between
      attentional matrices scores and N100 amplitude at Fz and Cz to standard stimuli
      in the passive condition was found in controls but not in patients. CONCLUSIONS:
      In RBD there are minimal event-related potentials (ERPs) abnormalities involving
      the early stages of information processing. SIGNIFICANCE: ERPs are not sensitive
      to pre or sub-clinical cognitive abnormalities in RBD. In alternative, these
      findings might support the existence of a truly idiopathic RBD syndrome.

PMID- 17208047
TI  - Event-related potentials predict the outcome of the vegetative state.

PMID- 17208049
TI  - Eating disorders in the 21st century: identification, management, and prevention
      in obstetrics and gynecology.
AB  - Eating disorders are extremely common and carry a high degree of medical and
      psychiatric morbidity. These disorders are challenging to treat because many
      patients deny their symptoms, have poor motivation to change, and can become
      frustrating to the clinician. Case identification based upon suggested screening
      questions and ongoing management of medical consequences are important roles for
      the obstetrician/gynecologist involved in the care of these patients. This
      chapter discusses the benefits and limitations of contemporary treatment, special
      populations at risk (e.g. athletes, diabetics), and screening guidelines for
      office practice. Signs, symptoms, laboratory abnormalities, and the perils of
      associated psychiatric illness are briefly reviewed. Patients do respond to a
      comprehensive, integrated treatment plan that includes nutritional stabilization,
      psychotherapy, and pharmacotherapy. Collaboration between all professionals
      involved in the patient's care is essential for state-of-the-art care. Those
      patients who become pregnant or wish to become pregnant pose certain additional
      treatment considerations. Ongoing and future research aimed at understanding how
      eating disorders develop - and may be prevented by early identification and
      education - will result in enhanced knowledge of these life-threatening and often
      chronic illnesses in the 21st century.

PMID- 17208048
TI  - Predicting coma and other low responsive patients outcome using event-related
      brain potentials: a meta-analysis.
AB  - OBJECTIVE: A meta-analysis was performed to estimate the predictive power (odd
      ratio, OR) for awakening of auditory event-related potential (ERP) components in
      low responsive patients with stroke or hemorrhage, trauma, anoxic, post
      operative, and metabolic encephalopathy etiologies. METHODS: We reviewed MEDLINE
      and analyzed citations for retrieved articles. Logistic regressions were applied
      on patient samples (Glasgow Coma Scale <12) across and for separate etiologies.
      RESULTS: For stroke and hemorrhage the ORs with 95% confidence intervals were:
      2.05 [1.12-3.75] (N100), 4.47 [1.92-10.44] (MMN), 10.29 [2.00-52.79] (P300), for
      trauma: 1.63 [0.70-3.80] (N100), 4.72 [1.35-16.44] (MMN), 12.89 [4.82-34.43]
      (P300), anoxic: 8.03 [2.83-22.75] (N100), 15.50 [4.27-56.26] (MMN), 5.93 [2.38
      14.77] (P300), post-operative: 10.66 [1.98-57.50] (N100), metabolic
      encephalopathy: 2.12 [0.34-13.13] (N100), 3.60 [0.28-46.36] (MMN), 7.71 [0.75
      79.77] (P300), and all etiologies: 2.85 [1.91-4.27] (N100), 6.53 [3.55-12.01]
      (MMN), and 8.79 [4.88-15.83] (P300). Based on six N100 studies (N=548 patients),
      five MMN studies (N=470), and six P300 studies (N=313), the N100, MMN, or P300,
      when present, significantly predicted awakening, P300 and MMN being significantly
      better predictors than N100. CONCLUSIONS: The MMN and P300 appear to be reliable
      predictors of awakening. SIGNIFICANCE: The prognostic assessment of low
      responsive patients with auditory ERP should take into account both MMN and P300.

PMID- 17208050
TI  - Kon-Tiki revisited.

PMID- 17208051
TI  - Subaortic dynamic obstruction: a contributing factor to haemodynamic instability
      in tako-tsubo syndrome?
AB  - We present a case of transient apical ballooning with haemodynamic instability in
      a female patient with normal coronaries and a history of poorly controlled
      systemic arterial hypertension. There was dynamic obstruction of the outflow
      tract and moderate secondary mitral regurgitation at presentation. These were due
      to systolic anterior motion of the mitral valve, which normalised gradually with
      the recovery of left ventricular function, and to a 'sigmoid' septum. Mid-cavity
      obstruction is potentially an important contributory factor to the haemodynamic
      instability sometimes encountered in this syndrome.

PMID- 17208052
TI  - Lack of bufadienolides in the skin secretion of red bellied toads,
      Melanophryniscus spp. (Anura, Bufonidae), from Uruguay.
AB  - The South-American red bellied toads (Melanophryniscus spp.) belonging to the
      Bufonidae family contain toxic alkaloids in their skin, predominantly of the
      pumiliotoxin group. Whole animal methanolic extracts of individual specimens of
      three species (Melanophryniscus atroluteus, M. devincenzii, and M. montevidensis)
      were analyzed for the presence of toad specific bufadienolides and
      indolalkylamines (serotonin derivatives) by HPLC-electrospray (ESI)-MS-TOF. No
      bufadienolides, but few bufotenines, mainly dehydrobufotenine, were detected in
      the extracts in variable amounts. The concentration of the dehydrobufotenine in
      the extracts seems to be species specific. Whereas M. atroluteus and M.
      montevidensis contain very low or trace amounts, M. devincenzii specimens exhibit
      high concentrations of this indolalkylamine. In comparison, analysis of extracts
      from Bufo arenarum (Uruguay) and from B. bufo (Germany) confirmed the presence of
      bufadienolides as well as of bufotenine derivatives. Tadpoles of both species
      exhibited a different pattern: extracts from B. arenarum tadpoles contained only
      dehydrobufotenine, but those from B. bufo tadpoles bufotoxin and two alkylamines.
      Melanophryniscus toads appear not to be able to compensate the high variability
      of toxic skin alkaloids by producing defensive bufadienolides.

PMID- 17208053
TI  - Molecular and functional evolution of Tetrahymena metallothioneins: new insights
      into the gene family of Tetrahymena thermophila.
AB  - A new metallothionein (MTT-5) gene isoform has been cloned and characterized from
      the ciliate Tetrahymena thermophila. Its amino acid sequence shows only limited
      similarity with other Tetrahymena MTs. To investigate the transcriptional
      activity of this gene toward heavy metals (Cd, Cu, Zn), mRNA levels were
      evaluated by real-time quantitative PCR. Results show that the three metals
      induce different MTT-5-mRNA levels, Cd treatment eliciting the most effective
      induction in the first 30 min. Phylogenetic analyses of all Tetrahymena MT
      protein sequences revealed that MTT-5 is closely related to Cd-induced isoforms
      and quite separate from Cu-induced ones. Our results indicate that Cd and Cu MTs
      diverged early in evolution, before the speciation event which separated the
      Tetrahymena borealis group from the Tetrahymena australis group. The mutation
      rate in the Tetrahymena MT group is heterogeneous, being very low for MT-1 and
      MTT-1 and higher for the other isoforms, particularly for MTT-5, which shows the
      maximum divergence among the Cd-induced MTs. This observation, together with the
      evidence of its inducibility by Zn - a unique condition among T. thermophila MTs 
      indicates that MTT-5 underwent a particular evolutionary history, independent of
      other MT isoforms.

PMID- 17208054
TI  - Induction of mixed-function oxygenase system and antioxidant enzymes in the coral
      Montastraea faveolata on acute exposure to benzo(a)pyrene.
AB  - Components of the cytochrome P(450) monooxygenase system (MFO) and antioxidant
      enzymes were investigated in the coral Montastraea faveolata exposed to the
      organic contaminant benzo(a)pyrene (B(a)P). For bioassays the corals were exposed
      to increasing concentrations of B(a)P (0.01 and 0.1 ppm) for 24 and 72 h, with
      water renewal every 24 h. Enzymatic activity of catalase (CAT), superoxide
      dismutase (SOD) and glutathione S-transferase (GST) were measured in host (polyp)
      and hosted (zooxanthellae) cells. NADPH cytochrome c reductase activity and
      contents of cytochrome P(450) and P(420) were only measured in the polyp.
      Antioxidant enzymes CAT and SOD in polyps and zooxanthellae and GST in polyps
      increased significantly at the highest concentration and maximum time of
      exposure. Cytochrome P(420) was found in all colonies, and the cytochrome P(450)
      content was greatest in the colonies from the highest concentrations of
      contaminant. NADPH cytochrome c reductase activity and the concentration of
      pigments did not vary between treatments. This is the first report of the
      induction of both detoxifying mechanisms, the MFO system and antioxidant enzymes
      on acute exposure to an organic contaminant in the reef-constructing coral
      species M. faveolata.

PMID- 17208055
TI  - Emotional and cognitive information processing in web-based medical education.
AB  - The patient-physician relationship can be conceived as a process of structuring
      an ill-structured emotional-cognitive problem. So, new methods should be
      developed in order to capture the relations among emotions and cognitions, and
      physicians should be educated to recognize the influence of emotions on medical
      decision-making. The paper describes GRASP, an e-learning application based upon
      the assumption that cognitions and emotions are dual concepts. The results of a
      blended e-learning experiment are shown. The students were confronted with a role
      playing based illness narrative. Their observations were segmented into
      information units, and uploaded on the e-learning system DVLN. The set of
      information units was then transformed into a bipartite graph, and analysed by
      means of STRUCTURE, an application aimed at grasping the structure of the
      relations among a set of "objects". The results were compared with Correspondence
      Analysis. The implications for medical education, medical reasoning, and medical
      record design are discussed.

PMID- 17208056
TI  - UV-induced apoptosis in XPG-deficient fibroblasts involves activation of CD95 and
      caspases but not p53.
AB  - Mildly affected individuals from xeroderma pigmentosum complementation group G
      (XP-G) possess single amino acid substitutions in the XPG protein that adversely
      affects its 3' endonuclease function in nucleotide excision repair. More serious
      mutations in the XPG gene generate truncated or unstable XPG proteins and result
      in a particularly early and severe form of the combined XP/CS complex. Following
      UV irradiation, cells from such XP-G/CS patients enter apoptosis more readily
      than other DNA repair-deficient cells. Here, we explore the mechanisms by which
      UV triggers the apoptotic cell death program in XP-G and XP-G/CS primary
      fibroblasts. Activation of the CD95 signalling pathway occurs within minutes and
      it is the earliest detectable post-UV event in such cells. This is rapidly
      followed by activation of caspase-8 then caspase-3. Several hours later caspase-9
      becomes activated and the mitochondrial membrane potential drops, but without any
      obvious prior release of cytochrome c. Although p53 accumulates in XPG-deficient
      cells after UV irradiation, use of RNA interference demonstrates that p53 is not
      required for their UV-induced apoptotic response. p53 ablation of wild-type
      fibroblasts reduces MDM2 mRNA levels, inhibits accumulation of the 90kDa/92kDa
      Mdm2 isoforms, and prevents the nuclear relocalisation of Mdm2 after UV
      treatment. The same post-UV effects occur in XPG-deficient cells that express
      normal p53 levels. These results emphasise the importance of the extrinsic
      apoptotic pathway and aberrant Mdm2 events for the severe UV-induced apoptosis of
      XPG-deficient primary fibroblasts. XP-G/CS cells constitutively overexpress the
      pro-apoptotic Bax protein and a long isoform of the E2F1 transcription factor
      that controls S phase entry, which may prime them to enter apoptosis very readily
      after UV irradiation.

PMID- 17208057
TI  - Measurement of circulating nitrite and S-nitrosothiols by reductive
      chemiluminescence.
AB  - Considerable disparities in the reported levels of basal human nitrite and S
      nitrosothiols (RSNO) in blood have brought methods of quantifying these nitric
      oxide (NO) metabolites to the forefront of NO biology. Ozone-based
      chemiluminescence is commonly used and is a robust method for measuring these
      species when combined with proper reductive chemistry. The goal of this article
      is to review existing methodologies for the measurement of nitrite and RSNO by
      reductive chemiluminescence. Specifically, we discuss in detail the measurement
      of nitrite and RSNO in biological matrices using tri-iodide and
      copper(I)/cysteine-based reduction methods coupled to chemiluminescence. The
      underlying reaction mechanisms, as well as the potential pitfalls of each method
      are discussed.

PMID- 17208058
TI  - The role of the S1 binding site of carboxypeptidase M in substrate specificity
      and turn-over.
AB  - The influence of the P1 amino acid on the substrate selectivity, the catalytic
      parameters K(m) and k(cat), of carboxypeptidase M (CPM) (E.C. 3.4.17.12) was
      systematically studied using a series of benzoyl-Xaa-Arg substrates. CPM had the
      highest catalytic efficiency (k(cat)/K(m)) for substrates with Met, Ala and
      aromatic amino acids in the penultimate position and the lowest with amino acids
      with branched side-chains. Substrates with Pro in P1 were not cleaved in similar
      conditions. The P1 substrate preference of CPM differed from that of two other
      members of the carboxypeptidase family, CPN (CPN/CPE subfamily) and CPB (CPA/CPB
      subfamily). Aromatic P1 residues discriminated most between CPM and CPN. The type
      of P2 residue also influenced the k(cat) and K(m) of CPM. Extending the substrate
      up to P7 had little effect on the catalytic parameters. The substrates were
      modelled in the active site of CPM. The results indicate that P1-S1 interactions
      play a role in substrate binding and turn-over.

PMID- 17208059
TI  - An unusual cause of lymph nodes enlargement.

PMID- 17208061
TI  - Reduction of body iron stores and the prevention of type 2 diabetes.

PMID- 17208063
TI  - Does purity of supplements count?

PMID- 17208064
TI  - Effect on heart rate of bitter orange, caffeine, and exercise.

PMID- 17208066
TI  - Salt intake and cardiovascular mortality.

PMID- 17208068
TI  - Treatment of erythrocytosis associated with obesity hypoventilation syndrome.

PMID- 17208069
TI  - Aspirin resistance: is it real? Is it clinically significant?

PMID- 17208070
TI  - From here to eternity: a unified kinetic model for the pathophysiology of
      atherosclerotic events.
AB  - Two operative pathophysiological models underlie the clinical management of
      ischemic heart disease: a physical model founded on the magnitude of vascular
      stenosis and a biochemical model founded on the inflammatory processes within the
      atherosclerotic plaque. Despite their complementary natures, these 2 models are
      implicitly competitive--the stenotic model supporting the primacy of aggressive
      interventional procedures and the inflammatory model supporting the primacy of
      conservative medical management. We unified these alternative perspectives
      through a kinetic model that characterizes the pathophysiology of cardiovascular
      events as a network of exponential transitions between the inflammatory and
      stenotic states. According to this model, the prevalence of the normative
      (nonstenotic and noninflammatory) state falls exponentially, while the
      prevalences of the inflammatory and stenotic states rise to a peak and then fall
      off exponentially. According to this model, event rate increases as a complex
      function of both myocardial ischemia and vascular inflammation. Although the
      model has yet to be prospectively validated, it provides a theoretical foundation
      for predicting the degree to which atherosclerotic events are due to inflammation
      versus stenosis and the degree to which they can thereby be prevented by
      treatment strategies directed at plaque stabilization or relief of ischemia.

PMID- 17208071
TI  - Outpatient management of survivors of acute coronary syndromes.
AB  - More patients are both suffering and surviving acute coronary syndromes. After
      hospital discharge, a host of interventions, including medications, therapeutic
      lifestyle changes, revascularization, and electrophysiologic devices improve
      quality of life and survival. Evidence-based management requires the general
      internist to have a working knowledge of these interventions and to identify
      patients whose outcomes would benefit from subspecialty referral.

PMID- 17208072
TI  - The traveling farm wife.

PMID- 17208073
TI  - Sure signs.

PMID- 17208074
TI  - Beat by beat variations.

PMID- 17208075
TI  - An alternate route: 64-slice CT diagnosis of pulmonary pseudosequestration.

PMID- 17208076
TI  - Antihypertensive medication adherence in the Department of Veterans Affairs.
AB  - PURPOSE: Adherence measures the extent to which patients take medications as
      prescribed by their health care provider. The control of hypertension is
      dependent on medication adherence and may vary on the basis of antihypertensive
      medication class and other factors. METHODS: The Department of Veterans Affairs'
      automated pharmacy database captures pharmacy medication use; International
      Classification of Diseases, 9th Revision, diagnostic codes; and laboratory and
      patient demographic data on a monthly basis. Hypertensive patients who used
      thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors,
      angiotensin receptor blockers, calcium channel antagonists, and alpha-blockers
      from July 2002 to December 2003 were studied. The first date of prescription
      filling for each patient within the date range was the index date from which fill
      and refill dates were collected for up to 18 months to calculate medication
      possession ratios and days out of medication ratios. Patients were categorized as
      adherent if the medication possession ratio was 80% or greater. Logistic
      regression was used to study the association of medication class, age, gender,
      ethnicity, Veterans Affairs facility, and co-diagnosis with diabetes,
      schizophrenia/psychosis, depression, and dementia with medication adherence.
      RESULTS: We studied 40,492 hypertensive patients taking at least one
      antihypertensive drug class. The average age per class ranged from 67.4 to 72.9
      years; 96% were male; and 51% were white, 8% were African-American, 4% were Asian
      American, and 3% were Hispanic. Unadjusted adherence rates based on the
      medication possession ratio ranged from 78.3% for thiazide diuretics to 83.6% for
      angiotensin receptor blockers (P<.001). The number of medications (either total
      or antihypertensive) and age were independent predictors of better adherence.
      Black ethnicity and depression were associated with worse adherence. CONCLUSIONS:
      Adherence rates with all antihypertensive medications were high. Although there
      were statistical differences by drug class, these differences were small.
      Ethnicity and depression identified groups that might benefit from programs to
      improve adherence.

PMID- 17208077
TI  - Effects of socioeconomic status on mortality after acute myocardial infarction.
AB  - PURPOSE: To assess the effects of socioeconomic status on mortality in patients
      with acute myocardial infarction. MATERIAL AND METHODS: We studied a
      retrospective cohort of 5622 patients who presented to a hospital emergency
      department with an initial episode of acute myocardial infarction between April
      1998 and March 2002 in the Province of Alberta, Canada. Our main outcome measure
      was 1-year all-cause mortality following the index emergency department visit; we
      used socioeconomic status (measured by neighborhood median household income) as
      our main predictor after controlling for patient and hospital characteristics and
      revascularization. RESULTS: Socioeconomic status profoundly affected the rate of
      emergency department presentation and the process and outcome of acute myocardial
      infarction care. In patients belonging to the lowest versus the highest
      socioeconomic status quartile, the risk of presenting to the emergency department
      was 72% higher (P <.001); at 1 year, revascularization was lower (36% vs 48%, P
      <.001), and mortality higher (19.1% vs 9.1%, P <.001). Socioeconomic status was
      independently associated with 1-year mortality after adjustment for baseline
      characteristics and 1-year revascularization, and socioeconomic status was
      especially influential in non-revascularized patients. CONCLUSIONS: Given the
      influence of socioeconomic status on mortality after acute myocardial infarction
      and the key role of revascularization in modulating this relationship, our study
      has important implications for access to and process of cardiac care.

PMID- 17208078
TI  - A comparison of acute coronary syndrome care at academic and nonacademic
      hospitals.
AB  - PURPOSE: Although adherence to guidelines recommendations is assumed to be more
      difficult for nonacademic community hospitals, patterns of adherence have not
      been evaluated by hospital type. We sought to identify hospital characteristics
      associated with high levels of adherence in order to gain insight into successful
      processes of care. METHODS: From January 2001 through March 2004, we analyzed
      data from 86,042 patients in the CRUSADE Initiative with high-risk non-ST-segment
      elevation acute coronary syndromes (NSTE ACS) defined by positive cardiac markers
      or ischemic ST-segment changes. Academic sites were defined by Council of
      Teaching Hospital affiliation in the American Hospital Association database.
      Adherence was determined for each hospital based on guidelines recommendations
      for the use of 4 acute (<24 hrs) and 5 discharge therapies in patients without
      contraindications. Multivariable modeling was used to standardize hospital
      estimates for patient characteristics and control for clustering within centers.
      RESULTS: A total of 60,285 patients were admitted to nonacademic hospitals
      (n=355), and 25,757 were admitted to academic hospitals (n=125). Academic
      hospitals were larger (median 500 vs 268 beds, P <.001) and more often had bypass
      services (88% vs 60%, P <.001). Composite adherence to recommended therapies was
      slightly higher at academic vs. nonacademic hospitals (median 77.8% vs 73.7%, P
      <0.01), and variance in individual hospital performance was greater among
      nonacademic sites. Nonacademic hospitals accounted for 15 of the 20 highest
      performing sites and 19 of the 20 lowest performing sites. In-hospital clinical
      outcomes, including cardiogenic shock, stroke, and death were similar for
      patients admitted to both types of hospital. CONCLUSION: Adherence to American
      College of Cardiology and American Heart Association (ACC/AHA) guidelines for
      NSTE ACS care at academic hospitals is slightly higher than at nonacademic
      hospitals; however there is significant room for improvement within both systems.
      The larger performance variation in care among nonacademic hospitals highlights
      the need for continued emphasis on consistent care processes.

PMID- 17208079
TI  - Trend in mortality after stroke with atrial fibrillation.
AB  - PURPOSE: To evaluate trend in mortality in stroke associated with atrial
      fibrillation, we examined mortality trend after stroke with atrial fibrillation
      by calendar year period (1980-1984, 1985-1989, 1990-1994, 1995-1999, and 2000
      2002). We estimated trends separately for each sex in unadjusted analyses. We
      also adjusted for age, comorbid conditions, and general trend in mortality in the
      background population. METHODS: We identified all individuals, aged 40-89 years,
      with an incident diagnosis of stroke of any nature (ischemic or hemorrhagic) 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 multivariate Cox proportional hazards regression analysis
      to estimate trend in mortality. RESULTS: Incident stroke with a previous or
      concomitant diagnosis of nonvalvular atrial fibrillation or flutter was diagnosed
      in 24,470 subjects (11,554 men and 12,916 women). During 34,405 years of
      observation, 9237 men died, and during 35,381 years of observation, 10,827 women
      died. The hazard ratio for mortality after stroke in the last 3-year period
      compared with the first 5-year period was .65 (95% confidence interval [CI], .61
      .71) in men and .69 (95% CI, .64-.74) in women. CONCLUSIONS: We observed a
      substantially better survival in men and women after stroke associated with
      atrial fibrillation or flutter in Denmark during the years 1980 to 2002. However,
      we could not control for changes in admission practice, diagnostic performance,
      or treatment.

PMID- 17208080
TI  - The expectation effect and cardiac pacing for refractory vasovagal syncope.
AB  - BACKGROUND: Clinical trials of pacing for vasovagal syncope have shown
      conflicting results. We performed a meta-analysis to determine whether permanent
      pacemaker therapy prevents refractory vasovagal syncope. METHODS: Randomized
      trials comparing pacemaker therapy with medical therapy, usual care, placebo, or
      different pacing algorithms in the prevention of recurrent vasovagal syncope were
      considered. The primary endpoint was first recurrence of syncope. RESULTS: Nine
      randomized trials (2 double blind, 7 open label or single blind) were included.
      There was significant heterogeneity when all 9 trials were pooled (P=.0009 and
      I(2)=69.6%), reflecting methodological diversity in blinding and the nature of
      the control therapy. When pooled by trial methodology, heterogeneity was no
      longer apparent. Permanent pacing reduced the risk of recurrent syncope in
      unblinded studies (odds ratio [OR] 0.09, 95% confidence interval [CI], 0.04 to
      0.22) and in studies comparing pacemaker algorithms (OR 0.04, 95% CI, 0.0 to
      0.23). No effect was seen in double-blinded trials (OR 0.83, 95% CI, 0.41 to
      1.70). Awareness that a permanent pacemaker was implanted and functional was
      associated with a significant 'expectation' effect, which itself reduced the risk
      of recurrent syncope (OR 0.16, 95% CI, 0.06 to 0.40, P=.0001). Results were
      similar when restricted to patients with a marked cardioinhibitory response on
      baseline tilt table testing. CONCLUSION: The results of small, preliminary trials
      have overestimated the treatment effect of pacemakers due to a lack of blinding
      of physicians and patients. Blinded trials suggest that the apparent response is
      due to a strong expectation response to pacing.

PMID- 17208081
TI  - Use of heparins in Non-ST-elevation acute coronary syndromes.
AB  - PURPOSE: We describe the use of antithrombotic therapy in the management of
      patients with acute coronary syndromes. METHODS: Patients from the Global
      Registry of Acute Coronary Events, a multinational coronary disease registry,
      were characterized according to the early and continued use of low-molecular
      weight heparin, unfractionated heparin, any crossover of heparin therapy (change
      in early vs late heparin treatment), and no heparin treatment. Hospital outcomes
      were analyzed according to the heparin treatment and the timing of percutaneous
      coronary interventions. RESULTS: Data from 23,172 patients with non-ST-segment
      elevation myocardial infarction or unstable angina were analyzed. A total of 8791
      patients were treated with low-molecular-weight heparin within the first 24 hours
      and continued thereafter; 4076 patients received unfractionated heparin; 2953
      patients received neither heparin therapy; and 7352 patients received crossover
      heparin treatment. Concomitant treatment, including early or late percutaneous
      coronary intervention, varied according to the type of heparin therapy. Patients
      treated with a crossover therapy were more likely to undergo percutaneous
      coronary intervention. The rates of major bleeding and death were lower with low
      molecular-weight heparin (1.4% and 1.8%, respectively) compared with
      unfractionated heparin (1.9% and 2.5%, respectively), crossover heparin (2.0% and
      2.3%, respectively), or neither heparin (1.5% and 2.4%, respectively).
      CONCLUSIONS: There is significant variability in heparin use in patients with
      acute coronary syndromes. Heparin type and use seem to be related to the timing
      and use of percutaneous coronary interventions. The early use of low-molecular
      weight heparin in the setting of an acute coronary syndrome is associated with
      better short-term outcomes.

PMID- 17208082
TI  - Self-managed long-term low-molecular-weight heparin therapy: the balance of
      benefits and harms.
AB  - PURPOSE: A substantial clinical need exists for an alternate to vitamin K
      antagonists for treating deep vein thrombosis in many patients. Long-term low
      molecular-weight heparin (LMWH), body-weight adjusted, avoids anticoagulant
      monitoring and may be associated with less bleeding. We evaluated the
      effectiveness and safety of long-term LMWH compared with vitamin K antagonist
      therapy in a broad spectrum of patients with proximal vein thrombosis. METHODS:
      We performed a multicenter, randomized, open-label clinical trial using objective
      outcome measures comparing therapy for 3 months. Outcomes were assessed at 3 and
      12 months. RESULTS: Of 737 patients, 18 of 369 receiving tinzaparin (4.9%) had
      recurrent venous thromboembolism at 3 months compared with 21 of 368 (5.7%)
      receiving usual care (absolute difference, -0.8%, 95% confidence interval -4.1
      2.4). Hemorrhagic complications occurred less frequently in the LMWH group
      largely because of less minor bleeding: 48 of 369 patients (13.0%) versus 73 of
      368 patients (19.8%) receiving usual-care anticoagulation (absolute difference 
      6.8%; P = .011; risk ratio = 0.66). New major bleeding events ceased early (by
      day 23, P = .034) for patients receiving LMWH but persisted throughout the study
      treatment interval for patients receiving vitamin K antagonist therapy. No
      mortality advantage was shown for LMWH. CONCLUSION: Our study shows that LMWH is
      similar in effectiveness to the usual-care vitamin K antagonist treatment for
      preventing recurrent venous thromboembolism in a broad spectrum of patients. It
      causes less harm and enhances the clinicians' therapeutic options for patients
      with proximal deep vein thrombosis. Our findings reported here suggest the
      possibility of a broader role for long-term LMWH in selected patients.

PMID- 17208083
TI  - The utility of gestures in patients with chest discomfort.
AB  - PURPOSE: Patient gestures are thought to be useful in determining the etiology of
      chest discomfort. We sought to determine the utility of certain patient gestures
      in the diagnosis of ischemic chest discomfort or myocardial infarction. METHODS:
      We performed a prospective observational study of 202 patients admitted with
      chest discomfort. Patients were observed for the Levine Sign (clenched fist to
      the chest), the Palm Sign (palm of the hand to the chest), the Arm Sign (touching
      the left arm), and, as an indicator of nonischemic chest discomfort, the Pointing
      Sign (pointing with 1 finger). RESULTS: Prevalences of the Levine, Palm, Arm, and
      Pointing Signs were 11%, 35%, 16%, and 4%, respectively. Using troponin levels
      and results of functional studies and coronary angiograms as reference standards,
      none of the sensitivities of the signs exceeded 38%. Specificities of the Levine
      and Arm Signs ranged between 78% and 86%, but the positive predictive values did
      not exceed 55%. The Pointing Sign had a specificity of 98% for evidence of
      nonischemic chest discomfort, and the positive predictive value of a negative
      troponin was 88%. The diameter of discomfort significantly correlated with
      certain gestures. Larger chest pain diameters were associated with evidence of
      myocardial ischemia. CONCLUSIONS: Although certain gestures are exhibited by
      patients presenting with chest discomfort, they generally have poor test
      characteristics. The Pointing Sign has a high specificity for nonischemic chest
      discomfort, but a low prevalence. The gestures may communicate the size of the
      chest discomfort, with larger areas suggestive of ischemia.

PMID- 17208084
TI  - Trends in management, hospital and long-term outcomes of elderly patients with
      acute myocardial infarction.
AB  - PURPOSE: The number of elderly patients with acute myocardial infarction (AMI) is
      growing rapidly, and their early and postdischarge mortality is high. Several
      studies have reported a decline in mortality after myocardial infarction;
      however, the magnitude of the decline among the elderly has not been fully
      investigated. METHODS: We assessed trends in management, in-hospital, and long
      term outcomes of 1475 elderly patients (aged > or =75 years, 42% women)
      hospitalized with AMI in all 25 operating coronary care units in Israel between
      1992 and 2002, from our prospective nationwide biennial surveys. RESULTS: Between
      1992 and 2002, a significant increase was observed in the use of acute
      reperfusion therapy (27%-48%), coronary angiography (6%-47%), percutaneous
      coronary intervention (3%-33%), coronary bypass (2%-8%), aspirin (53%-88%), beta
      blockers (18%-65%), angiotensin-converting enzyme inhibitors (26%-63%), and lipid
      lowering drugs (0%-43%). These changes were associated with a 42% reduction in 30
      day mortality (27.6%-16.1%; adjusted odds ratio 0.57; 95% confidence interval
      [CI], 0.36-0.93). One-year cumulative mortality declined by 20% (37%-29%;
      adjusted odds ratio 0.74; 95% CI, 0.49-1.13). CONCLUSIONS: The management of
      elderly patients with AMI changed substantially during the last decade. This
      change was associated with a significant reduction in early mortality, whereas
      cumulative 1-year mortality improved only slightly. Better adherence to in
      hospital management guidelines and better implementation of postdischarge health
      policy may further decrease mortality and morbidity in the elderly after AMI.

PMID- 17208085
TI  - Use of disease-modifying therapies in patients hospitalized with heart failure: a
      population-based perspective.
AB  - BACKGROUND: Little data are available about the hospital management of patients
      with decompensated heart failure (HF) with individual and combination medical
      therapies, particularly from the more generalizable perspective of a population
      based investigation. The purpose of our study was to describe the use of
      different cardiac medications in 2463 patients with new-onset HF who were
      discharged from all greater Worcester, Massachusetts, hospitals during 2000.
      METHODS: On the basis of a review of medical records, we examined the prescribing
      of 2 classes of cardiac medications that have been shown to improve the long-term
      prognosis of patients with HF (angiotensin pathway inhibitors and beta-blockers).
      We also examined the use of 2 therapies commonly used to improve the symptomatic
      status of patients with acute HF (diuretics and digoxin). RESULTS: The mean age
      of the study sample was 76 years, and 57% were women. Approximately 1 in 5
      patients were not prescribed beta-blockers or angiotensin inhibitors during their
      index hospitalization, whereas 1 in 3 patients were discharged with both of these
      effective cardiac medications. Diuretics were prescribed for virtually all
      patients (98%), followed by the use of digoxin in approximately half of patients
      (48%). The receipt of both beta-blockers and angiotensin pathway inhibitors was
      associated with several demographic, medical history, and clinical factors.
      Patients treated with both effective cardiac medications were also more likely to
      be counseled to monitor or modify several lifestyle factors that have been shown
      to be effective adjuncts to the medical management of patients with HF.
      CONCLUSIONS: Considerable opportunity remains for the more optimal hospital
      management of patients with decompensated HF.

PMID- 17208086
TI  - Impact of NSAIDS on mortality and the effect of preexisting coronary artery
      disease in US veterans.
AB  - BACKGROUND: Evidence indicates increased risk of cardiovascular events with
      certain nonsteroidal anti-inflammatory drug (NSAID) use; however, less is known
      about NSAID use and mortality. In addition, it is unclear whether risks observed
      with NSAIDs are modified by coronary artery disease (CAD). The association
      between NSAID exposure and mortality, cardiovascular, and cerebrovascular events
      was examined. METHODS: A nested case-control study in a cohort of 565,451 US
      veterans with a diagnosis of osteoarthritis was conducted. The cohort was divided
      into those with preexisting CAD (16,869 cases) and those without (11,912 cases).
      Up to 20 controls were selected for each case. RESULTS: The average age of
      participants was 69.8 years (non-CAD) and 71.8 years (CAD). Relative to no
      exposure, adjusted odds ratios for cardiovascular or cerebrovascular events for
      any NSAID were 1.14 (95% confidence interval [CI], 1.08-1.21) in the non-CAD
      group and 1.18 (95% CI, 1.11-1.27) in the CAD group. Exposure to NSAIDs was
      associated with a decreased risk of all-cause mortality in both the non-CAD
      (0.72, 95% CI, 0.68-0.77) and CAD (0.79, 95% CI, 0.73-0.86) groups. CONCLUSIONS:
      As in previous reports, there was an increased risk of cardiovascular and
      cerebrovascular events for NSAIDs. However, NSAID exposure was associated with a
      reduced risk of death. This study raises important questions about NSAIDs in
      patients with osteoarthritis given that they seem to increase the risk of
      cardiovascular events but decrease overall mortality.

PMID- 17208087
TI  - Saving primary care.

PMID- 17208089
TI  - Listening to those who are new to the specialty.

PMID- 17208090
TI  - Tooth size, tooth stability, and the master's thesis.

PMID- 17208092
TI  - Turning ideas into action.

PMID- 17208094
TI  - Acromegaly.

PMID- 17208096
TI  - Anchorage loss with and without implants during canine retraction.

PMID- 17208097
TI  - A cephalometric study of Class II malocclusions treated with mandibular surgery.
AB  - INTRODUCTION: Class II malocclusion is often associated with retrognathic
      mandible. Some of these problems require surgical correction. The purposes of
      this study were to investigate treatment outcomes in patients with Class II
      malocclusions whose treatment included mandibular advancement surgery and to
      identify predictors of good outcomes. METHODS: Pretreatment and posttreatment
      cephalometric radiographs of 90 patients treated with mandibular advancement
      surgery by 57 consultant orthodontists in the United Kingdom before September
      1998 were digitized, and cephalometric landmarks were identified. Paired samples
      t tests were used to compare the pretreatment and posttreatment cephalometric
      values for each patient. For each cephalometric variable, the proportion of
      patients falling within the ideal range was identified. Multiple logistic
      regression analysis was performed to identify predictors of achieving ideal range
      outcomes for the key skeletal (ANB and SNB angles), dental (overjet and
      overbite), and soft-tissue (Holdaway angle) measurements. RESULTS: An overjet
      within the ideal range of 1 to 4 mm was achieved in 72% of patients and was more
      likely with larger initial ANB angles. Horizontal correction of the incisor
      relationship was achieved by a combination of 75% skeletal movement and 25%
      dentoalveolar change. An ideal posttreatment ANB angle was achieved in 42% of
      patients and was more likely in females and those with larger pretreatment ANB
      angles. Ideal soft-tissue Holdaway angles (7 degrees to 14 degrees ) were
      achieved in 49% of patients and were more likely in females and those with
      smaller initial SNA angles. Mandibular incisor decompensation was incomplete in
      28% of patients and was more likely in females and patients with greater
      pretreatment mandibular incisor proclination. Correction of increased overbite
      was generally successful, although anterior open bites were found in 16% of
      patients at the end of treatment. These patients were more likely to have had
      initial open bites. CONCLUSIONS: Mandibular surgery had a good success rate in
      normalizing the main dental and skeletal relationships. Less ideal soft-tissue
      profile outcomes were associated with larger pretreatment SNA-angle values,
      larger final mandibular incisor inclinations, and smaller final maxillary incisor
      inclinations. The use of mandibular surgery to correct anterior open bite was
      associated with poor outcomes.

PMID- 17208098
TI  - Long-term stability of Class III treatment: rapid palatal expansion and
      protraction facemask vs LeFort I maxillary advancement osteotomy.
AB  - INTRODUCTION: The aim of this retrospective cephalometric study was 3-fold: (1)
      to compare the effects and long-term stability of protraction facemask treatment
      with untreated Class III controls, (2) to compare the long-term stability of
      early protraction facemask treatment with later surgical maxillary advancement
      with LeFort I osteotomy, and (3) to determine whether early intervention with
      protraction facemask is an effective treatment modality or whether surgical
      treatment after cessation of growth should be advocated. MATERIALS: The sample
      consisted of 34 consecutively treated white patients with Class III malocclusions
      characterized by maxillary deficiency. The protraction sample consisted of 17
      children (8 boys, 9 girls). The surgical sample consisted of 17 adults (10 men, 7
      women). The protraction group was also compared with a control group of white
      subjects with untreated Class III malocclusions. Lateral cephalograms were taken
      at T1 (initial records), T2 (end of functional appliance treatment or 2 weeks
      postsurgery), and T3 (7 years 6 months postprotraction or 1 year 5 months
      postsurgery). Means and standard deviations were calculated for descriptive
      cephalometric measurements. ANOVA was used to assess the differences between and
      within the protraction and surgery groups at T1, T2, and T3. The Tukey
      studentized range test was performed to determine the source of the difference.
      In addition, paired t tests were used to compare the differences between the
      protraction group and the matched controls as well as between the surgery group
      and the matched controls. RESULTS: In the protraction group, there was continued
      favorable growth of the maxilla, even after the removal of the protraction
      facemask. From T2 to T3, the maxilla continued to move anteriorly in the
      protraction patients more so than in the control groups, which had decreases in
      the intermaxillary measurements (ANB angle and Wits appraisal) over time. The
      surgical group remained stable from T2 to T3 in all measurements studied.
      CONCLUSIONS: The most striking findings of this study were the general similarity
      between the protraction and the surgical groups at T3 and the overall stability
      of both treatment modalities over time.

PMID- 17208099
TI  - Effects of human relaxin on orthodontic tooth movement and periodontal ligaments
      in rats.
AB  - INTRODUCTION: The rate-limiting step in orthodontic treatment is often the
      rapidity with which teeth move. Using biological agents to modify the rate of
      tooth movement has been shown to be effective in animals. Relaxin is a hormone
      present in both males and females. Its main action is to increase the turnover of
      fibrous connective tissues. Thus, relaxin might increase the amount and rate of
      tooth movement through its effect on the periodontal ligament (PDL). The purpose
      of this study was to measure the effect of relaxin on orthodontic tooth movement
      and PDL structures. METHODS: Bilateral orthodontic appliances designed to tip
      maxillary molars mesially with a force of 40 cN were placed in 96 rats. At day 0,
      the animals were randomized to either relaxin or vehicle treatment. Twelve rats
      in each group were killed at 2, 4, 7, and 9 days after appliance activation.
      Cephalograms were taken at appliance placement and when the rats were killed.
      Tooth movement was measured cephalometrically in relation to palatal implants.
      Fractal analysis and visual analog scale assessments were used to evaluate the
      effect of relaxin on PDL fiber organization at the tension sites in histologic
      sections. The in-vitro testing for PDL mechanical strength and tooth mobility was
      performed by using tissue from an additional 20 rats that had previously received
      the same relaxin or vehicle treatments for 1 or 3 days (n = 5). RESULTS: Both
      groups had statistically significant tooth movement as functions of time.
      However, relaxin did not stimulate significantly greater or more rapid tooth
      movement. Fractal and visual analog scale analyses implied that relaxin reduced
      PDL fiber organization. In-vitro mechanical testing and tooth mobility
      assessments indicated that the PDL of the mandibular incisors in the relaxin
      treated rats had reduced yield load, strain, and stiffness. Moreover, the range
      of tooth mobility of the maxillary first molars increased to 130% to 170%, over
      vehicle-treated rats at day 1. CONCLUSIONS: Human relaxin does not accelerate
      orthodontic tooth movement in rats; it can reduce the level of PDL organization,
      reduce PDL mechanical strength, and increase tooth mobility at early time points.

PMID- 17208100
TI  - Orthodontic treatment experience and prevalence of malocclusion traits in an
      Icelandic adult population.
AB  - INTRODUCTION: The objectives of this study were to record the extent of
      orthodontic treatment and the prevalence of occlusal anomalies in an adult sample
      in Iceland. METHODS: The study was based on a random sample of 829 subjects, 342
      men and 487 women, aged 31 to 44 years, who completed questionnaires about their
      orthodontic treatment experiences and were available for clinical examination.
      RESULTS: Complete dentitions in both jaws were present in 52.8% of the women and
      45.3% of the men at the examinations. Significantly higher percentages of the
      women had received orthodontic treatment of some kind (24.3% compared with 16.9%
      for the men) and treatment with fixed appliances (16.0% compared with 9.5% for
      the men). Malocclusion traits were recorded with a standardized method,
      describing sagittal and vertical incisor relationships, sagittal and transverse
      molar relationships, and mandibular and maxillary space conditions. The results
      showed that 45.5% of the subjects had no malocclusions, 33.9% had 1 malocclusion
      trait, and 20.5% had 2 to 4 traits. The most frequent malocclusion traits were
      distal molar occlusion (27.7%), mandibular anterior crowding (13.4%), molar
      crossbite (11.9%), excessive overbite (11.8%), maxillary anterior crowding
      (7.1%), mesial molar occlusion (6.9%), and excessive overjet (5.3%). The
      prevalences of mandibular overjet, mesial occlusion, and scissors-bite were
      significantly higher in the men than in the women. CONCLUSIONS: The prevalences
      of malocclusion traits were similar in treated and untreated subjects, except for
      a significantly lower prevalence of overjet and a higher prevalence of molar
      crossbite in the treated group. Comparison with other studies showed low
      prevalences of overjet, overbite, open bite, and maxillary and mandibular spacing
      and crowding; other variables fell within the ranges of prevalence in previous
      surveys.

PMID- 17208101
TI  - Clinical use of miniscrew implants as orthodontic anchorage: success rates and
      postoperative discomfort.
AB  - INTRODUCTION: In this study, we evaluated the clinical usefulness of miniscrews
      as orthodontic anchorage. We examined their success rates, analyzed factors
      associated with their stability, and evaluated patients' postoperative pain and
      discomfort with a retrospective questionnaire. METHODS: Seventy-five patients,
      116 titanium screws of 2 types, and 38 miniplates were retrospectively examined.
      Each patient was given a questionnaire that included a visual analog scale to
      indicate discomfort after implantation. RESULTS: The success rate for each type
      of implant was greater than 80%. The analysis of 79 miniscrews with a 1.3-mm
      diameter showed no significant correlations between success rate and these
      variables: age, sex, mandibular plane angle, anteroposterior jaw-base
      relationship, control of periodontitis, temporomandibular disorder symptoms,
      loading, and screw length. Most patients receiving titanium screws or miniplates
      with mucoperiosteal-flap surgery reported pain, but half of the patients
      receiving miniscrews without flap surgery did not report feeling pain at any time
      after placement. In addition, patients with miniscrews reported minimal
      discomfort due to swelling, speech difficulty, and difficulty in chewing.
      CONCLUSIONS: Miniscrews placed without flap surgery have high success rates with
      less pain and discomfort after surgery than miniscrews placed with flap surgery
      or miniplates placed with either procedure.

PMID- 17208102
TI  - Osseointegrated implants with pendulum springs for maxillary molar distalization:
      a cephalometric study.
AB  - INTRODUCTION: Maxillary molar distalization is a common treatment approach for
      patients with Class II malocclusions who do not require extractions. Despite the
      many advantages of pendulum appliances, the maxillary incisors and premolars tend
      to shift mesially as the maxillary molars move distally. The purpose of this
      study was to investigate anchorage loss in patients treated with palatal
      osseointegrated implants combined with pendulum springs. METHODS: Pretreatment
      and posttreatment lateral cephalometric films of 30 consecutively treated
      patients were examined. One group (n = 15) had been treated with conventional
      pendulum appliances, and the other group (n = 15) was treated with palatal
      osseointegrated implants combined with pendulum springs. RESULTS: In the pendulum
      group, significant distal tipping of the maxillary first molars and mesial
      tipping of the maxillary premolars were noted. Distalization of the maxillary
      first molars, mesialization of the maxillary first premolars, and proclination of
      the maxillary left central incisor were significant in the linear measurements.
      In the implant group, the distal tipping of the maxillary first molars and first
      premolars and the increases in SNGoGn, FMA, Na Me, and Na ANS were significant.
      Intergroup comparisons showed that changes in the maxillary first premolars,
      maxillary central incisors, and vertical measurements were significant.
      CONCLUSIONS: The use of palatal osseointegrated implants is reliable and provides
      absolute anchorage.

PMID- 17208103
TI  - Management of postorthodontic demineralized white lesions with microabrasion: a
      quantitative assessment.
AB  - INTRODUCTION: The aim of this study was to quantify changes in postorthodontic
      demineralized enamel lesion surface areas after microabrasion. METHOD: The study
      group comprised 8 orthodontic patients (mean age,17.3 years) with multiple
      decalcified enamel lesions after fixed orthodontic therapy. Two demineralized
      areas were randomly selected for interventive treatment in each patient.
      Microabrasion was undertaken on these lesions by using a well-accepted 18%
      hydrochloric acid and pumice technique. Standardized intraoral images were taken
      of the lesions before and immediately after microabrasion. Image-processing
      software was used to quantify (mm2) the visible areas of the demineralized
      lesions before and after microabrasion. The total labial surface area of each
      tooth was also determined, and the area affected by demineralization was
      expressed as a percentage of total tooth surface. Images were reanalyzed a month
      later to determine the repeatability of the method. RESULTS: Microabrasion
      significantly reduced visible enamel demineralization (P < .001, paired t test).
      The mean reduction in lesion size after treatment was 83% (SD, 8.2%; range, 61%
      92%). The quantification methodology was found to be highly repeatable with an
      intraclass correlation coefficient of 0.98. CONCLUSIONS: Microabrasion is an
      effective treatment approach for the cosmetic improvement of long-standing
      postorthodontic demineralized enamel lesions.

PMID- 17208104
TI  - Physical properties of root cementum: Part 9. Effect of systemic fluoride intake
      on root resorption in rats.
AB  - INTRODUCTION: Orthodontically induced inflammatory root resorption is a common
      complication in orthodontic treatment. Fluoride has been reported to have a
      beneficial effect against root resorption in dental traumatology. The effect of
      fluoride on orthodontically induced inflammatory root resorption has not been
      investigated. This study was undertaken to investigate the effect of fluoride on
      the incidence of root resorption. METHODS: Thirty-two female 8-week-old Wistar
      rats were separated into 4 groups. Two groups (6 rats per group) were controls;
      they did not undergo orthodontic tooth movement. The other 2 groups (10 rats per
      group) had orthodontic tooth movement consisting of activated 100-g closing
      nickel-titanium coils (NiTi 10-000-06, GAC International, Bohemia, NY) connecting
      the mandibular first molar to the incisors. Fluoridated water (100 ppm) was given
      ad libitum to 1 control and 1 experimental group. The other 2 groups received
      deionized water. After 2 weeks, the animals were killed, and the samples were
      harvested. Resorption craters were scanned with a Micro CT (SkyScan 1072,
      Aartselaar, Belgium). Software analysis of the scanned samples provided a
      volumetric measurement of the resorption craters on the mandibular molar cementum
      surface. RESULTS: Resorption sites were found in the control samples, especially
      on the distal surfaces; this could be attributed to normal physiological tooth
      drift. Resorption sites were significantly (P <.05) increased in the groups
      receiving orthodontic tooth movement. CONCLUSIONS: Fluoride reduces the size of
      resorption craters, but the effect is variable and not statistically significant
      (P >.05).

PMID- 17208106
TI  - Assessing the American Board of Orthodontics objective grading system: digital vs
      plaster dental casts.
AB  - INTRODUCTION: The purposes of this study were to determine whether the American
      Board of Orthodontics objective grading system (ABO OGS) can be assessed
      accurately from digital dental casts and whether there are statistical
      differences between digital and plaster dental casts in scoring the ABO OGS.
      METHODS: Thirty posttreatment plaster dental casts were selected and scanned by
      OrthoCAD (Cadent, Carlstadt, NJ) to produce 30 corresponding digital dental
      casts. The plaster and digital casts were compared by using the criteria of the
      ABO OGS. Because the data were ordinal, a nonparametic statistical analysis was
      used. RESULTS: The Wilcoxon test for paired samples showed significant
      differences between the plaster and digital casts for occlusal contacts, occlusal
      relationships, and total scores (P <.05). No significant differences were found
      for alignment, marginal ridges, overjet, and interproximal contacts. Buccolingual
      inclination was not included in this study because of inability to perform proper
      measurements with the OrthoCAD program. Mean differences of points deducted
      ranged from .03 point for marginal ridges to 5.07 points for the total score. The
      variable with the most points deducted related to occlusal relationships, and the
      fewest points were deducted for interproximal contacts. CONCLUSIONS: Based on
      this study, the current OrthoCAD program (version 2.2) was not adequate for
      scoring all parameters as required by the ABO OGS.

PMID- 17208105
TI  - Three-dimensional cone-beam computed tomography for assessment of mandibular
      changes after orthognathic surgery.
AB  - INTRODUCTION: The purpose of this study was to assess alterations in the 3
      dimensional (3D) position of the mandibular rami and condyles in patients
      receiving either maxillary advancement and mandibular setback or maxillary
      surgery only. METHODS: High-resolution cone-beam computed tomography scans were
      taken of 21 patients before and after orthognathic surgery. Ten patients with
      various malocclusions underwent maxillary surgery only, and 11 Class III patients
      received maxillary advancement and mandibular setback. Presurgery and postsurgery
      3D models were registered on the surface of the cranial base. A new tool was used
      for graphical overlay and 3D display with color maps to visually assess the
      locations and to quantify positional changes in the posterior border of the
      mandibular rami and condyles between superimposed models. RESULTS: The average
      displacements in condylar position were small--0.77 mm (SD, 0.12 mm) and 0.70 mm
      (SD, 0.08 mm)--for 2-jaw and 1-jaw surgeries, respectively (not significant, P
      >.05). All 2-jaw surgery patients had backward rotational displacements of the
      mandibular rami (mean, 1.98 mm; SD, 1.03 mm), with a maximum surface distance
      change of > or =2 mm in 8 of 11 subjects. For the 1-jaw surgery, all subjects had
      small backward rotational displacements of the mandibular rami (mean, 0.78 mm;
      SD, 0.25 mm), with only 1 subject having a maximum surface distance change > or
      =2 mm. The difference in mean backward rotational displacement was statistically
      significant (P <.01). CONCLUSIONS: The visualization of 3D model superimposition
      clearly identified the location, magnitude, and direction of mandibular
      displacement. The 3D imaging allowed quantification of vertical, transverse, and
      anteroposterior ramus displacement that accompanied mandibular, but not maxillary
      only, surgery.

PMID- 17208107
TI  - Class II subdivision malocclusion types and evaluation of their asymmetries.
AB  - INTRODUCTION: The primary objective of this study was to determine, by means of
      frontal photographic evaluation, the distribution of the 2 main types of Class II
      subdivision malocclusions. The secondary objective was to compare the
      dentoskeletal asymmetries in these 2 types with a group of normal-occlusion
      subjects by using submentovertex and posteroanterior radiographs. METHODS: The
      experimental group included 44 untreated Class II subdivision malocclusion
      subjects with a mean age of 15.3 years. The control group included 30 subjects
      with normal occlusions with a mean age of 22.4 years. All had full complements of
      permanent teeth up to the first molars and had not received orthodontic
      treatment. Type 1 Class II subdivision malocclusion is coincidence of the
      maxillary dental midline with the facial midline and deviation of the mandibular
      midline. Type 2 has the opposite characteristics. The frontal photographs were
      evaluated subjectively by 2 examiners. In the submentovertex and posteroanterior
      radiographs, symmetry was assessed by measuring the relative difference in the
      spatial positions of dentoskeletal landmarks between the right and left sides.
      Independent t tests were used to compare the dentoskeletal asymmetries of types 1
      and 2 with the normal-occlusion group. RESULTS AND CONCLUSIONS: The results
      showed that 61.36% had type 1, 18.18% had type 2 Class II subdivision
      malocclusion, and 20.45% had mixed characteristics. The predominant asymmetric
      dentoalveolar characteristics of both types of Class II subdivision malocclusions
      were evident when individually compared with a normal-occlusion control group.
      There was a tendency for the type 1 subjects to have greater mandibular asymmetry
      than type 2, as compared with the control group.

PMID- 17208108
TI  - Correlations between cephalometric and facial photographic measurements of
      craniofacial form.
AB  - INTRODUCTION: The purpose of this study was to compare craniofacial measurements
      from cephalometric radiographs with analogous measurements from standardized
      facial photographs. METHODS: The sample consisted of 326 subjects (168 white, 158
      black) enrolled in a genetic epidemiological family study of sleep behavior.
      Traditional lateral cephalograms and standardized facial photographs were taken
      of each subject. Three angular, 3 linear, total face height, and lower face
      height cephalometric measurements were compared with 4 angular and 4 linear
      measurements from standardized photographs. Descriptive statistics for all
      measurements in the entire sample and for the racial subgroups were computed.
      Pearson product moment correlation coefficients were computed between analogous
      measurements, and intraclass correlation coefficients were calculated from
      repeated measurements on the photographs. RESULTS: The reliability of the
      photographic technique was excellent, with all measurements having intraclass
      correlation coefficients above 0.90. However, the correlations between analogous
      photographic and cephalometric measurements were lower and varied between 0.356
      and 0.643. The highest correlations were observed for lower facial height and
      mandibular length, 0.643 and 0.562, respectively. In the black group, the
      correlations between cephalometric and photographic measurements of mandibular
      length and lower facial height were 0.676 and 0.690, respectively. Both were
      higher than those for white subjects, 0.399 and 0.577, respectively. CONCLUSIONS:
      Both linear and angular measurements useful for characterizing facial morphology
      can be reliably measured from facial photographs. However, only moderate
      correlations with analogous cephalometric measures were found. Therefore,
      standardized photographs and cephalograms most likely measure different aspects
      of facial morphology and cannot be used interchangeably. Cephalometrics remains
      the method of choice for clinical patient care, whereas photographs might be
      better for large-scale epidemiological studies, especially if there is a need for
      a low-cost, noninvasive method that be used in diverse clinical and field
      settings.

PMID- 17208109
TI  - Assessment of bisphenol-A release from orthodontic adhesives.
AB  - INTRODUCTION: The aim of this study was to quantitatively characterize the
      bisphenol-A (BPA) released from orthodontic adhesives after artificial
      accelerated aging. METHODS: A chemically cured, no-mix adhesive and a visible
      light-cured adhesive were bonded to 40 stainless steel brackets divided in 2
      groups of 20 brackets each. In total, 3 series of specimens were prepared for
      each adhesive-bracket group. All specimens were immersed in alcohol to induce
      accelerated aging. Samples of eluent removed from each group at 1 day and at 1,
      3, and 5 weeks after aging were processed with high-pressure liquid
      chromatography; all assays were performed in triplicate, and the results were
      averaged. RESULTS: No trace of BPA was identified for either adhesive across all
      time intervals, implying that, if present, the amount of BPA did not exceed the
      detection limit of the analytical technique (0.1 ppm or 0.1 microg/L).
      CONCLUSIONS: BPA release from light-cured or chemically cured, no-mix adhesives
      did not reach the 0.1 ppm level. Estrogenicity assays are required to clarify the
      potential estrogenicity of adhesives, whereas formulation of benzoic ring-free,
      high molecular weight monomers might eliminate the concerns associated with the
      use of Bis-GMA.

PMID- 17208110
TI  - Orthodontic appliance design.

PMID- 17208111
TI  - Oculofaciocardiodental syndrome and orthodontics.
AB  - Radiculomegaly of a tooth is a rare condition. When it is associated with other
      dental abnormalities and congenital cataracts, the condition is called
      oculofaciocardiodental syndrome, which is characterized by congenital cataracts,
      dental anomalies, many minor facial dysmorphic features, and congenital heart
      defects. So far, only 20 cases have been reported. In this article, the case of a
      14-year-old girl with congenital cataracts, radiculomegaly of the maxillary
      central incisors and the maxillary and mandibular canines, dilacerations of the
      mandibular incisors, and open apexes of many teeth is presented. Orthodontic
      alignment of the dental arches was completed with light forces so as not to cause
      shortening of the roots or ankylosis.

PMID- 17208112
TI  - Retreatment of a patient who presented with condylar resorption.
AB  - This case report describes the retreatment of a patient whose initial
      nonextraction treatment several years earlier had been unsuccessful. When she
      sought new treatment, she had an open bite, proclined incisors, and severe
      temporomandibular joint derangement with almost complete resorption of the
      condyles. The new treatment, which included extractions and surgery, gave her
      balanced and harmonious facial proportions, a Class I occlusion with normal
      overjet and overbite, and a healthy dentition. There was no further loss of
      condylar tissue and the temporomandibular joints were asymptomatic.

PMID- 17208113
TI  - Photo archiving, cephalometric analyses, and information sharing on the Internet.
AB  - The method we use to collect, store, and share dental records of our patients is
      rapidly becoming digital. Many programs have been designed to run on a single
      computer or local network to handle various tasks, including cephalometric
      analysis and orthodontic treatment planning. Selecting a system can be complex,
      requiring consideration of capital investment costs and subscription or update
      fees, as well as the ease (or difficulty) of installing the system and learning
      to use it. cephX (cephX, Inc, Las Vegas, Nev) is an Internet-based digital data
      storage and retrieval service for cephalometric analyses, photographic storage,
      and online data sharing. Users pay for services as they are used, eliminating the
      need to buy new hardware or software.

PMID- 17208114
TI  - Litigation, legislation, and ethics. Evidence-based data: are they admissible?

PMID- 17208115
TI  - The Mediterranean diet story illustrates that "why" questions are as important as
      "how" questions in disease explanation.
AB  - The discovery of the cardioprotective properties of the Mediterranean diet is one
      of the great successes of epidemiology, and as a result elites around the globe
      now regularly consume Mediterranean products like olive oil. Although
      biochemical, clinical, and epidemiological studies have at least partly revealed
      how various components of this diet may protect the cardiovascular system, the
      reasons why this protection is conferred by a "Mediterranean" but not by many
      other European diets have not received so much attention. A plausible hypothesis
      is that, because of a combination of physico-geographical and socioeconomic
      circumstances, the variety of plant and animal food traditionally consumed by
      populations on the European shores of the Mediterranean Sea is relatively similar
      to that of the food available to the hunter-gatherers from whom we descend. Our
      organ systems have evolved to work optimally on such a diet, and have not had the
      chance to adapt to a diet containing, for example, more saturated fats and trans
      fatty acids, and less antioxidants and fiber. Understanding why the Mediterranean
      diet is cardioprotective is important for finding dietary solutions within the
      physico-geographical and socioeconomic constraints of the areas in which
      populations actually live, for example, by taking advantage of the
      cardioprotective properties of their traditional diets. This may in the longer
      run lead to a more sustainable approach to cardiovascular disease prevention.

PMID- 17208116
TI  - Exercise proves effective in a systematic review of work-related complaints of
      the arm, neck, or shoulder.
AB  - OBJECTIVE: Interventions such as physiotherapy and ergonomic adjustments play a
      major role in the treatment of most work-related complaints of the arm, neck,
      and/or shoulder (CANS). We evaluated whether conservative interventions have a
      significant impact on outcomes for work-related CANS. STUDY DESIGN AND SETTING: A
      systematic review was conducted. Only (randomized) trials studying interventions
      for patients suffering from work-related CANS were included. Interventions may
      include exercises, relaxation, physical applications, and workplace adjustments.
      Two authors independently selected the trials, assessed methodological quality,
      and extracted data. RESULTS: We included 26 studies (in total 2,376 patients); 23
      studies included patients with chronic nonspecific complaints. Over 30
      interventions were evaluated and 7 main subgroups of interventions could be
      determined, of which the subgroup "exercises" was the largest one. Overall, the
      quality of the studies appeared to be poor. CONCLUSION: There is limited evidence
      for the effectiveness of exercises when compared to massage, adding breaks during
      computer work, massage as add-on treatment to manual therapy, manual therapy as
      add-on treatment to exercises, and some keyboards in people with carpal tunnel
      syndrome when compared to other keyboards or placebo. For other interventions no
      clear effectiveness could be demonstrated.

PMID- 17208117
TI  - An absence of pediatric randomized controlled trials in general medical journals,
      1985-2004.
AB  - OBJECTIVE: There are numerous potential barriers to conducting randomized
      controlled trials (RCTs) in children. The purpose of this study was to compare
      the quantity, trends over time, characteristics, and quality of pediatric RCTs
      published in general medical journals (GMJs) with adult RCTs. STUDY DESIGN AND
      SETTING: We conducted an electronic search of adult and pediatric RCTs from 1985
      2004 and a manual search of published RCTs in the year 2000 in five high-impact
      GMJs (New England Journal of Medicine, Journal of the American Medical
      Association [JAMA], the Lancet, British Medical Journal [BMJ], Canadian Medical
      Association Journal [CMAJ]). Linear trends were identified and the 1-year sample
      was analyzed for publication characteristics (location of recruitment, sample
      size, number of centers, funding sources, and results) and quality scoring (Jadad
      score, intention-to-treat analysis, and citation frequency since publication).
      RESULTS: Adult RCTs increased by 4.71 RCTs/year (95% confidence interval (CI)
      3.62-5.80; P<0.001), which was significantly higher (P<0.0001) than pediatric
      RCTs, which increased by 0.4 RCTs/year (95% CI -0.02 to 0.9; P=0.06). Adult RCTs
      were more likely to be hospital-based (P=.001) and to involve more centers in
      multicenter studies (P=0.02). Quality scores were similar, although adult RCTs
      were cited more frequently (P=0.003). CONCLUSION: There may be significant
      barriers to the publication of high-quality pediatric RCTs in GMJs.

PMID- 17208118
TI  - BLISS index for analyzing knee osteoarthritis trials data.
AB  - OBJECTIVES: Different pain thresholds were investigated, using the WOMAC Pain
      Scale (WOMAC-P) to determine if they could differentiate between treatment groups
      (hylan G-F 20 vs. appropriate care) at low and very low levels of state
      attainment in patients with knee osteoarthritis (OA). A method, termed the BLISS
      (Bellamy et al. Low Intensity Symptom State-attainment) Index, for analyzing OA
      knee clinical trials data, was proposed. STUDY DESIGN AND SETTING: Five analyses
      were performed: time to first BLISS day, BLISS days over 12 months, patients with
      a BLISS response at month 12, patients with a BLISS response at any time, and
      number of BLISS periods over 12 months. For each analysis, five levels of WOMAC-P
      were examined: <or=5 normalized units (NU), <or=10, <or=15, <or=20, and <or=25
      (higher=more pain). RESULTS: More patients in the hylan G-F 20 group achieved
      BLISS states in all five analyses. These differences were statistically
      significant for all pain threshold levels except <or=5 NU. CONCLUSION: Five
      methods of measuring BLISS attainment using four prespecified threshold levels of
      pain were able to statistically discriminate between treatment groups. This
      method may potentially provide an approach, to defining which patients not only
      improve but also achieve a good state of health, at low and very low levels of
      pain intensity. BLISS-10 is a therapeutically attainable very low symptom state
      at which clinically important, statistically significant between-group
      differences are detectable, and therefore may provide a benchmark against which
      therapeutic interventions can be assessed. However, the value to patients, of
      this and other low and very low intensity pain states, requires further
      elaboration.

PMID- 17208119
TI  - A lifestyle program for treated hypertensives improved health-related behaviors
      and cardiovascular risk factors, a randomized controlled trial.
AB  - OBJECTIVE: To assess effects of a cognitively based program on health-related
      behaviors and cardiovascular risk factors in overweight drug-treated
      hypertensives. STUDY DESIGN AND SETTING: In a clinical trials center, volunteers,
      recruited by advertisement, were randomized to usual care (N=118) or to a 4-month
      program (N=123) incorporating weight loss; a low-sodium diet, high in fruit,
      vegetables, and fish; and increased physical activity. Diet, physical activity,
      weight, blood lipids, glucose, and insulin were measured at 4 and 16 months.
      RESULTS: Ninety-eight usual care and 106 program participants completed the 4
      month assessment; 90 and 102, respectively, completed follow-up. Using intention
      to-treat analysis, relative to usual care, net changes with the program at 4
      months were as follows: dietary fat (-2.6% energy; P<0.001); sodium (-290mg/d;
      P=0.004); energy (-313mJ/d; P=0.005); fish (+2.1 serves/wk; P<0.001); vegetables
      (+3.0 serves/wk; P<0.001); physical activity (+37min/wk; P=0.004); weight (
      2.8kg; P<0.001); waist girth (-3.1cm; P<0.001); total cholesterol (-0.2mmol/L;
      P=0.017); and triacylglycerols (-0.12mmol/L; P=0.002). One year later, net
      changes included dietary fat (-2.2% energy; P<0.001); sodium (-150mg/d; P=0.029);
      fish (+2.0 serves/wk; P<0.001); vegetables (+4.3 serves/wk; P<0.001); weight (
      2.5kg; P=0.001); waist girth (-3.1cm; P<0.001); high-density lipoprotein
      cholesterol (+0.03mmol/L; P=0.031). CONCLUSION: Improvements in behaviors and
      risk factors, several maintained long term, suggest the potential for long-term
      benefits in hypertensives.

PMID- 17208120
TI  - Present-at-admission diagnoses improved mortality risk adjustment among acute
      myocardial infarction patients.
AB  - OBJECTIVE: Hospital mortality outcomes for acute myocardial infarction (AMI)
      patients are a focus of quality improvement programs conducted by government
      agencies. AMI mortality risk-adjustment models using administrative data
      typically adjust for baseline differences in mortality risk with a limited set of
      common and definite comorbidities. In this study, we present an AMI mortality
      risk-adjustment model that adjusts for comorbid disease and for AMI severity
      using information from secondary diagnoses reported as present at admission for
      California hospital patients. STUDY DESIGN AND SETTING: AMI patients were
      selected from California hospital administrative data for 1996 through 1999
      according to criteria used by the California Hospital Outcomes Project Report on
      Heart Attack Outcomes, a state-mandated public report that compares hospital
      mortality outcomes. We compared results for the new model to two mortality risk
      adjustment models used to assess hospital AMI mortality outcomes by the state of
      California, and to two other models used in prior research. RESULTS: The model
      using present-at-admission diagnoses obtained substantially better discrimination
      between predicted survival and inpatient death than the other models we
      considered. CONCLUSION: AMI mortality risk-adjustment methods can be meaningfully
      improved using present-at-admission diagnoses to identify comorbid disease and
      conditions related closely to AMI.

PMID- 17208121
TI  - Diagnosis-dependent misclassification of infections using administrative data
      variably affected incidence and mortality estimates in ICU patients.
AB  - OBJECTIVE: To determine the accuracy of hospital discharge diagnoses in
      identifying severe infections among intensive care unit (ICU) patients, and
      estimate the impact of misclassification on incidence and 1-year mortality. STUDY
      DESIGN AND SETTING: Sepsis, pneumonia, and central nervous system (CNS)
      infections among 7,615 ICU admissions were identified using ICD-9 and ICD-10
      diagnoses from the Swedish hospital discharge register (HDR). Sensitivity,
      specificity, and likelihood ratios were calculated using ICU database diagnoses
      as reference standard, with inclusion in sepsis trials (IST) as secondary
      reference for sepsis. RESULTS: CNS infections were accurately captured
      (sensitivity 95.4% [confidence interval (CI)=86.8-100] and specificity 99.6%
      [CI=99.4-99.8]). Community-acquired sepsis (sensitivity 51.1% [CI=41.0-61.2] and
      specificity 99.4% [CI=99.2-99.6]) and primary pneumonia (sensitivity 38.2%
      [CI=31.2-45.2] and specificity 98.6% [CI=98.2-99.0]) were more accurately
      detected than sepsis and pneumonia in general. One-year mortality was accurately
      estimated for primary pneumonia but underestimated for community-acquired sepsis.
      However, there were only small differences in sensitivity and specificity between
      HDR and ICU data in the ability to identify IST. ICD-9 appeared more accurate for
      sepsis, whereas ICD-10 was more accurate for pneumonia. CONCLUSION: Accuracy of
      hospital discharge diagnoses varied depending on diagnosis and case definition.
      The pattern of misclassification makes estimates of relative risk more accurate
      than estimates of absolute risk.

PMID- 17208122
TI  - The SF-36 summary scores and their relation to mental disorders: physical
      functioning may affect performance of the summary scores.
AB  - BACKGROUND AND OBJECTIVES: The Medical Outcomes Study 36-item Short-Form Health
      Survey (SF-36) has been widely used as a generic measure of health status. It can
      be scored to provide either a profile of eight scores or two summary measures of
      health. Several studies demonstrated shortcomings of the summary scores in
      accurately reflecting patients' physical and mental health on the basis of
      subscale scores. The objective of this study was to compare and evaluate
      different scoring algorithms for the summary scores. METHODS: The analysis was
      based on data on 4,052 respondents from the German National Health Interview and
      Examination Survey. Mental disorders were assessed using a structured clinical
      interview. Logistic regression and receiver operating characteristic analyses
      were used to evaluate the association between the mental component scores and
      mental disorders. RESULTS: Subjects with mental disorders reported poorer quality
      of life on all SF-36 subscales and component scores compared to those without
      mental disorders. The presence of physical disorders resulted in different
      summary scores. The screening accuracy in detecting subjects with mental
      disorders was satisfactory for both mental summary scores. CONCLUSIONS: The
      summary scores should be evaluated in relation to the profile of the eight
      subscales. Physical functioning should be evaluated carefully when comparing
      health status using summary scores.

PMID- 17208123
TI  - Family history of cancer provided by hospital controls was satisfactorily
      reliable.
AB  - OBJECTIVE: Our aim was to investigate the reliability of the information on
      family history of cancer in first-degree relatives in a hospital-based case
      control study. STUDY DESIGN AND SETTING: We re-interviewed at home 294 controls
      of an Italian hospital-based case-control study on digestive tract neoplasms
      using the same questionnaire and compared the responses reported by these
      patients in the two settings. RESULTS: A satisfactory agreement between the two
      interviews was reported for family history of any cancer (kappa=0.7) and of
      cancers of the digestive tract (kappa=0.8). The agreement was apparently higher
      for esophageal and stomach cancers (kappa>0.8) than for intestinal cancers
      (kappa=0.6) and lower for lung cancer (kappa=0.5). We found a systematic tendency
      to report a history of cancer more frequently in the hospital setting than in the
      home setting. CONCLUSION: The present study showed a good reliability of data on
      family history of all cancers, including cancers of the digestive tract, provided
      by hospital controls through a structured interview-administered questionnaire.
      It suggests, moreover, that controls in the hospital setting tend to recall more
      often, and presumably more completely, a family history of cancer.

PMID- 17208124
TI  - Case-control prostate cancer screening studies should not exclude subjects with
      lower urinary tract symptoms.
AB  - OBJECTIVE: Prostate-specific antigen (PSA)/digital rectal exam (DRE) screening
      for prostate cancer has become standard medical practice; however, its
      effectiveness in terms of reducing prostate cancer mortality remains
      undetermined. Case-control screening studies may help determine screening
      efficacy, though the proper disposition of symptomatic subjects is unclear. This
      paper presents a prostate cancer-specific methodological modification for
      analyzing symptomatic case-control screening subjects. METHODS: Prostate cancer
      detection studies and case-control studies of PSA/DRE screening were reviewed,
      and the results for symptomatic and asymptomatic subjects were compared. RESULTS:
      Most PSA/DRE detection studies have found that the prostate cancer detection rate
      among symptomatic patients is the same as or lower than that among asymptomatic
      patients. Lower urinary tract symptoms (LUTS), often referred to as early
      prostate cancer symptoms, occur more often in benign prostatic hyperplasia (BPH),
      a more commonly diagnosed, nonmalignant disease. Screened symptomatic subjects
      are usually removed from the "screened" category in case-control studies even
      though BPH-related symptoms do not confer increased prostate cancer risk and odds
      ratios do not change with inclusion of symptomatic subjects in the analysis.
      CONCLUSION: Screened subjects with LUTS should remain in the "screened" category
      in case-control prostate cancer screening studies since these symptoms may not be
      associated with increased risk of prostate cancer or validity of the odds ratio.

PMID- 17208125
TI  - Millennium Cohort: enrollment begins a 21-year contribution to understanding the
      impact of military service.
AB  - OBJECTIVE: In response to health concerns of military members about deployment
      and other service-related exposures, the Department of Defense (DoD) initiated
      the largest prospective study ever undertaken in the U.S. military. STUDY DESIGN
      AND SETTING: The Millennium Cohort uses a phased enrollment strategy to
      eventually include more than 100,000 U.S. service members who will be followed up
      through the year 2022, even after leaving military service. Subjects will be
      linked to DoD and Veterans Affairs databases and surveyed every 3 years to obtain
      objective and self-reported data on exposures and health outcomes. RESULTS: The
      first enrollment phase was completed in July 2003 and resulted in 77,047
      consenting participants, well representative of both active-duty and
      Reserve/Guard forces. This report documents the baseline characteristics of these
      Cohort members, describes traditional, postal, and Web-based enrollment methods;
      and describes the unique challenges of enrolling, retaining, and following such a
      large Cohort. CONCLUSION: The Millennium Cohort was successfully launched and is
      becoming especially relevant, given current deployment and exposure concerns. The
      Cohort is representative of the U.S. military and promises to provide new insight
      into the long-term effects of military occupations on health for years to come.

PMID- 17208126
TI  - Millennium Cohort: the 2001-2003 baseline prevalence of mental disorders in the
      U.S. military.
AB  - OBJECTIVES: The 12-month prevalence of common mental illnesses in the United
      States is estimated to be 26%, accounting for an increasing fraction of all
      disability in the general population. The U.S. military is a unique group
      involved in response and defense during times of conflicts and disasters. The
      mental health of service members affects organizational productivity and
      effectiveness and is of great importance to the health of U.S. military members
      and public health in general. STUDY DESIGN AND SETTING: In the present report,
      the authors describe the baseline prevalence of mental disorders in a large U.S.
      military cohort, the Millennium Cohort, established for a 22-year longitudinal
      study of the health effects of military service. Using crude and weighted
      prevalence and multivariable logistic regression, the mental health morbidity of
      the Millennium Cohort is reported for various demographics. RESULTS: These
      analyses suggest that although the cohort compares favorably to other
      populations, there are military subpopulations, including women, younger, less
      educated, single, white, short-term service, enlisted, and Army members, who are
      at greater odds for some mental disorders. CONCLUSION: With ongoing U.S.
      involvement in combat operations around the world, these baseline data are
      essential to assessing long-term mental health morbidity in U.S. military service
      members.

PMID- 17208128
TI  - Sydenham Society: assessing the appropriateness of carotid endarterectomy.

PMID- 17208129
TI  - Sydenham Society: racial variations in carotid endarterectomy.

PMID- 17208130
TI  - Abbreviated guidelines for scoring the Cumulative Illness Rating Scale (CIRS) in
      family practice.

PMID- 17208132
TI  - Genitourinary oncology and its surgeon scientists: triumphant past, but does it
      have a future?

PMID- 17208133
TI  - Neoadjuvant therapy before radical prostatectomy: where have we been? Where are
      we going?
AB  - Prostate cancer is curable only when treated at an early stage, when the tumor is
      still localized to the prostate gland. However, even in apparent cases of
      clinically localized disease, unsuspected extracapsular disease may significantly
      increase the risk of primary treatment failure. This risk is especially high if
      the patient has > or =1 of the following risk factors: a serum prostate-specific
      antigen level of >20 ng/ml, a Gleason score of >7, locally advanced disease
      (clinical stage T3/T4), and extensive disease on prostate biopsy. Various
      regimens of neoadjuvant hormonal therapy, chemotherapy, or both have produced
      mixed results and, in general, have not significantly influenced the rate of
      disease relapse (as defined by prostate-specific antigen level) in high-risk
      patients with localized prostate cancer. In addition, anti-angiogenic agents,
      gene therapy, molecular targeting agents, and other promising new therapies have
      been investigated in a neoadjuvant setting with limited results. Therefore, this
      patient population continues to pose a therapeutic dilemma for physicians.

PMID- 17208134
TI  - Multilocular cystadenoma and cystadenocarcinoma of the prostate.
AB  - BACKGROUND: Multicystic prostatic tumors are rare, with only a few reported cases
      of prostatic cystadenoma and cystadenocarcinoma in the scientific literature.
      METHODS: A retrospective review of our tumor registry over the last 25 years
      identified 2 rare cystic tumors of the prostate: 1 multilocular cystadenoma and 1
      multilocular cystadenocarcinoma. RESULTS: The first case illustrates the clinical
      and pathologic features of prostatic multilocular cystadenoma. A 42-year-old man
      presented with a 16-cm suprapubic mass causing displacement of adjacent visceral
      organs. Pathologic examination after prostatectomy confirmed it to be a
      multilocular cystadenoma of the prostate. The patient's postoperative course was
      uneventful, and his serum prostate-specific antigen level remained at < or =0.04
      ng/ml throughout the course of his disease. In the second case, we present an 80
      year-old male presenting with a 12-cm cystic mass of the prostate. His serum
      prostate-specific antigen level remained at > or =9.0 ng/ml throughout the course
      of his disease. The tumor had an aggressive local growth pattern, with invasion
      into perirectal adipose tissue. This patient underwent a pelvic exenteration,
      followed by adjuvant systemic chemotherapy and complete androgen blockade.
      Despite aggressive treatment, he had 3 recurrences over 4 months but remains
      alive with disease at 23-month follow-up. CONCLUSIONS: Cystadenocarcinoma of the
      prostate is locally aggressive and should be included in the differential
      diagnosis of cystic lesions of the prostate.

PMID- 17208135
TI  - Changing comorbidity classification patterns at radical prostatectomy during a 10
      year period.
AB  - OBJECTIVE: To investigate the consistency of several comorbidity classifications
      and concomitant diseases at radical prostatectomy (RP) during a 10-year period.
      METHODS AND MATERIALS: In 1,297 patients who underwent RP between 1993 and 2002,
      age and several comorbidity classifications were derived from patient records and
      assigned to the year of surgery. Trends were evaluated using the Cochran-Armitage
      trend test. RESULTS: Parallel to an increasing frequency of RPs and a shift
      toward more organ-confined tumors (P = 0.0094), the proportion of patients aged >
      or =70 years increased (P = 0.0077). The proportion of the American Society of
      Anesthesiologists (ASA) Physical Status class 3 increased (P < 0.0001), whereas
      that of ASA class 1 decreased (P < 0.0001). A Charlson score > or =1 has been
      assigned with an increasing frequency (P = 0.0008), whereas the trend with a
      Charlson score of > or =2 did not reach statistical significance (P = 0.07). In
      contrast to the latter 2 classifications, no significant trends were observed
      with classifications related to diabetes mellitus and heart disease. CONCLUSIONS:
      This study shows that the application of the ASA classification may change
      significantly over time, whereas cardiac and diabetes-related conditions, as well
      as the Charlson score were apparently less sensitive to changing classification
      standards in the RP setting.

PMID- 17208136
TI  - Incidence and survival for testicular germ cell tumor in young males: a report
      from the Northern Region Young Person's Malignant Disease Registry, United
      Kingdom.
AB  - The incidence of testicular cancer has increased markedly in most developed
      countries, although the reasons for this are unclear. In this study, 253 patients
      with testicular cancer diagnosed younger than 25 years from 1968-1999 were
      identified from the Northern Region Young Persons' Malignant Disease Registry.
      The age-standardized incidence rate increased from 0.93 in 1968-1978 to 1.60 per
      100,000 in 1990-1999. The increase in incidence was confined to those patients
      >15 years old, with the rate in younger children remaining very low. The 5-year
      survival increased significantly from 46% (95% confidence interval [CI] 33% to
      58%) to 92% (95% CI 85% to 96%) during 1968-1999 and was significantly higher for
      seminoma than nonseminoma, 91% (95% CI 78% to 96%) and 77% (95% CI 70% to 82%),
      respectively. Although increased surveillance and public health campaigns
      designed to raise awareness of the disease and the advantages of self-examination
      should continue, further research is required into the etiology of this
      relatively common cancer among young males.

PMID- 17208137
TI  - Review of the M.D. Anderson experience in the treatment of bladder sarcoma.
AB  - OBJECTIVE: To assess the histologic subtypes, clinical presentations, treatment
      approaches, and treatment-related outcomes of patients with bladder sarcoma.
      METHODS: Between January 1985 and July 2004, 19 patients (12 men and 7 women)
      with primary bladder sarcoma were evaluated at the University of Texas M.D.
      Anderson Cancer Center. Median follow-up duration was 72 months (range 3-141).
      RESULTS: The median age of patients at presentation was 57 years (range 22-94).
      The histologic subtypes of bladder sarcoma were leiomyosarcoma (N = 14),
      angiosarcoma (N = 3), and unclassified sarcoma (N = 2). The clinical presentation
      consisted of gross, painless hematuria in 79% of patients, lower urinary tract
      symptoms in 16%, and microhematuria in 5%. The primary treatment modalities used
      were surgery in 16 (84%) patients, chemotherapy in 2 (11%), and palliation in 1
      (5%). The rate of local and distal recurrence was 16% and 53%, respectively. The
      most common sites of distant metastases were the lungs, bone, brain, and liver.
      The 5-year disease-specific survival rate was 59%, with a median survival
      duration of 6 years. There was no statistically significant difference in disease
      specific survival between patients with bladder leiomyosarcoma compared to other
      sarcoma subtypes (P = 0.149). Lymphovascular invasion (P = 0.03) and lymphatic
      metastasis (P = 0.03) were associated with disease-specific survival, and
      surgical margin status was associated with recurrence-free (P = 0.04), disease
      specific (P = 0.03), and overall survival (P = 0.005). CONCLUSIONS: Bladder
      sarcoma is a highly aggressive malignancy, regardless of its histologic subtype.
      Surgical margin status is an important determinant of survival.

PMID- 17208138
TI  - Phase II trial of capecitabine and rHu-interferon-alpha-2a in patients with
      metastatic renal cell carcinoma, limited efficacy, and moderate toxicity.
AB  - BACKGROUND: Capecitabine is an orally administered fluoropyrimidine that is
      converted to 5-fluorouracil by thymidine phosphorylase. In view of the recognized
      synergism of fluoropyrimidines with interferon-alpha (IFNalpha), a Phase II study
      to characterize the toxicity and efficacy of the combination of capecitabine and
      rHuIFNalpha-2a for the treatment of patients with renal cell carcinoma (RCC) was
      conducted. PATIENTS AND METHODS: Eligible patients had metastatic RCC, measurable
      disease, and no prior systemic therapy. A total of 32 patients were entered into
      the study. Histologic subtypes included clear cell (n = 28) and nonclear cell (n
      = 2). Histology was unknown for 2 patients. The first 14 patients were treated
      with capecitabine 1,000 mg/m(2) twice daily on days 1-14 and 22-36, combined with
      IFNalpha-2a 3.0 MU/m(2) subcutaneously 3 times weekly. Because of toxicity
      requiring dose reductions during the first cycle, the capecitabine dose was
      reduced to 825 mg/m(2) twice daily on days 1-14 and 22-36 in the subsequent 18
      patients. RESULTS: Responses were seen in 4 of 32 patients (12%) (95% confidence
      interval 4% to 29%), with 1 complete response and 3 partial responses. There were
      3 responses that occurred at the higher capecitabine starting dose level. Median
      response duration was 12 months (range 4.6-15.0). There were 12 patients (38%)
      who had stable disease for at least 2 cycles (duration 2.9 to 33.6+ months). One
      year survival was 63%. Toxicity was moderate to severe and required dose
      reductions in 88% of patients. There were 23 patients who had grade > or =3
      toxicity. CONCLUSION: The combination of capecitabine and IFNalpha-2a has limited
      activity in metastatic RCC and is associated with moderate-to-severe toxicity.

PMID- 17208139
TI  - Retroperitoneal mucinous cystadenocarcinoma in a man: case report and review of
      the literature.
AB  - In the English medical literature, 27 cases of primary retroperitoneal mucinous
      cystadenocarcinoma have been published. We report the second case of a primary
      retroperitoneal mucinous cystadenocarcinoma in a man. The patient was an 83-year
      old man, with a large 26 x 20 x 16-cm retroperitoneal cystic mass causing
      abdominal discomfort and cachexia, who underwent excision of the mass. Prior
      reports suggest that this type of tumor has an aggressive clinical course, and
      surgical excision is the treatment of choice. These rare tumors need to be
      included in the differential of retroperitoneal cystic tumors.

PMID- 17208141
TI  - A rationale for developing benchmarks for the treatment of muscle-invasive
      bladder cancer.
AB  - Benchmarks are established standards of operation developed by a given group or
      industry generally designed to improve outcomes. The health care industry is
      increasingly required to develop such standards and document adherence to meet
      demands of regulatory bodies. Although established practice patterns exist for
      the treatment of invasive bladder cancer, there is significant treatment
      variation. This article provides a rationale for the development of benchmarks in
      the treatment of invasive bladder cancer. Such benchmarks may permit advances in
      treatment application and potentially improve patient outcomes.

PMID- 17208142
TI  - Surgical benchmarks for the treatment of invasive bladder cancer.
AB  - Radical cystectomy is the gold standard for treatment of localized invasive
      bladder cancer in the United States. In recent years, there has been increasing
      focus on the importance of surgical technique as a factor that may influence the
      clinical and oncologic outcome of the operation, beyond the classically
      recognized patient and tumor-related factors. There is still insufficient high
      quality evidence to support the absolute standardization of the surgical
      technique or the establishment of firm benchmarks by which the individual surgeon
      can measure performance. However, there is considerable evidence suggesting that
      3 aspects of surgical technique have an impact on outcome: (1) Positive surgical
      margins nearly always result in ultimate cancer death. The rate of positive
      margins varies with surgeon experience as well as with cancer-specific variables.
      (2) The extent of lymphadenectomy has a significant impact on recurrence rates of
      the cancer, regardless of whether the lymph nodes are pathologically positive or
      not. (3) Higher volume surgeons have lower operative mortality and fewer positive
      surgical margins than low-volume surgeons. Higher volume hospitals also have
      lower operative mortalities and shorter hospital stays for patients who have
      undergone radical cystectomy. In this review, the authors evaluate the evidence
      supporting each of these statements and suggest potential areas of
      standardization of surgical technique that could translate into improved patient
      outcomes.

PMID- 17208143
TI  - Chemotherapy for muscle-invasive bladder cancer in the perioperative setting:
      current standards.
AB  - Radical cystectomy remains the gold standard treatment for muscle-invasive
      bladder cancer. Although surgery achieves excellent local control, within 5
      years, almost 50% of patients have a relapse and, subsequently, progression to
      systemic disease developing. Randomized trials of cisplatin-based chemotherapy
      regimens in the neoadjuvant setting have shown the potential to improve survival.
      Suboptimal trial design, insufficient numbers of patients, and lack of
      standardization of the chemotherapy regimens used have plagued adjuvant studies.
      Given the lethality of recurrent transitional cell carcinoma of the bladder,
      perioperative cisplatin-based chemotherapy should be considered a standard of
      care.

PMID- 17208144
TI  - Benchmarks achieved in the delivery of radiation therapy for muscle-invasive
      bladder cancer.
AB  - Radiation therapy has a multifaceted role in the treatment of muscle-invasive
      bladder cancer, from being a component of bladder sparing regimens to adjuvant
      therapy for patients after partial cystectomy, to palliative treatment in
      patients with metastatic disease. Here, we review the techniques currently used
      and the settings in which these techniques are applied. Advances in imaging and
      radiation delivery have allowed for definition of more precise treatment volumes,
      permitting the delivery of higher tumor doses and lesser doses to critical
      targets. Better tumor control, fewer therapeutic complications, and better
      quality of life outcomes are anticipated. In the United States, the most rapidly
      growing use of radiation in the treatment of bladder cancer is as a component of
      selective bladder conservation. It uses trimodality therapy, consisting of a
      maximal transurethral resection followed by concurrent chemotherapy and
      radiation. Careful cystoscopic surveillance by an experienced urologist ensures a
      prompt cystectomy at the fist sign of treatment failure. The majority of patients
      retain a well-functioning bladder with no survival decrement. Radiation therapy
      is also used as adjuvant therapy after partial cystectomy in select patients. In
      this setting, it decreases the risk of local or incisional recurrence. It is also
      used in patients with pelvic recurrences after cystectomy, often combined with
      concurrent chemotherapy. Radiation is a very effective palliative agent for
      patients with locally advanced or metastatic disease. It can palliate bleeding
      and pain for patients with local progression or alleviate pain from bony
      metastases.

PMID- 17208145
TI  - International comparisons of prostate cancer mortality rates with dietary
      practices and sunlight levels.

PMID- 17208161
TI  - Fundamentals of phototherapy for neonatal jaundice.
AB  - Phototherapy is the use of visible light for the treatment of hyperbilirubinemia
      in the newborn. This relatively common therapy lowers the serum bilirubin level
      by transforming bilirubin into water-soluble isomers that can be eliminated
      without conjugation in the liver. The dose of phototherapy largely determines how
      quickly it works; the dose, in turn, is determined by the wavelength of the
      light, the intensity of the light (irradiance), the distance between the light
      and the infant, and the body surface area exposed to the light. Commercially
      available phototherapy systems include those that deliver light via fluorescent
      bulbs, halogen quartz lamps, light-emitting diodes, and fiberoptic mattresses.
      Proper nursing care enhances the effectiveness of phototherapy and minimizes
      complications. Caregiver responsibilities include ensuring effective irradiance
      delivery, maximizing skin exposure, providing eye protection and eye care,
      carefully monitoring thermoregulation, maintaining adequate hydration, promoting
      elimination, and supporting parent-infant interaction.

PMID- 17208162
TI  - Part 1: a matter of size: evaluating the growth-restricted neonate.
AB  - The relative size of a neonate impacts many aspects of prenatal and postnatal
      surveillance and care. The designations of appropriate for gestational age, small
      for-gestational age, intrauterine growth restriction, and large-for-gestational
      age are systematic categorizations used to assess and monitor growth throughout
      pregnancy and delivery. Each abnormal growth descriptor aids in anticipating
      neonatal needs after birth because each has the potential for complications
      related to feeding, glucose utilization, short- and long-term growth, and
      development. Maternal risk factors that impact the neonate's size-related can
      have immediate implications in the delivery room as well as significant effects
      postnatally. Caring for neonates at risk for size complications requires
      knowledge based on prenatal and postnatal complications. Neonates must be
      carefully measured and plotted on growth charts to confirm a visual assessment of
      size. Each growth complication requires individual attention to detail and
      careful planning to maximize adequate postnatal growth and nutrition. Size
      matters when it comes to the health and welfare of neonates. Anticipatory
      guidance can improve outcomes in the neonate at risk for failure to thrive from
      size complications at birth. Part 1 of this article provides an overview of the
      size classifications and a discussion of clinical factors that are associated
      with or contribute to small-for-gestational age births. Once the neonate's size
      for gestational age is calculated, a focused physical assessment is described
      along with nursing care and prognostic implications. Part 2 will focus on the
      physical assessment, nursing care, prognosis, and complications associated with
      large-for-gestational-age neonates.

PMID- 17208163
TI  - Primer on the practice doctorate for neonatal nurse practitioners.
AB  - Recent advances in technology, research, and knowledge have amplified the need
      for longer and more in-depth education for neonatal nurse practitioners (NNPs).
      In this article we will briefly review the history of NNP's role and education,
      define the Doctor of Nursing Practice (DNP), and propose that the practice
      doctorate is the primary mechanism to meet that need and thus is the future of
      our profession. Doctor of Nursing Practice programs are designed to prepare the
      practitioner as an expert clinical NNP. Graduates obtain the highest level of
      practice expertise integrated with the ability to translate scientific knowledge
      into complex clinical interventions tailored to meet individual, family, and
      community health and illness needs. Doctor of Nursing Practice education also
      expands the scientific basis for practice and clinical practice education, and
      provides organization and system management and leadership, quality improvement,
      analytic methods to evaluate practice and apply evidence to practice, enhanced
      skills in information technology, health policy development, and
      interdisciplinary collaboration for enhanced patient outcomes.

PMID- 17208165
TI  - Fathers' perceptions of supportive behaviors for the provision of breast milk to
      premature infants.
AB  - PURPOSE: To explore fathers' perceptions of behaviors used to support the
      provision of breast milk to hospitalized premature infants. SUBJECTS: Sixteen
      English-speaking fathers who, each were at least 15 years of age, had a
      hospitalized premature infant between 24 and 32 weeks gestation and a partner who
      had decided to provide breast milk. DESIGN: As part of a larger, exploratory
      study, a qualitative descriptive study was conducted to analyze fathers'
      perceived contributions to the process of providing breast milk. METHODS: Fathers
      were interviewed with a semi-structured interview guide. All interviews were
      audiotaped, and verbatim transcripts were analyzed by using qualitative
      descriptive methods. MAIN OUTCOME MEASURE: Supportive behaviors as identified by
      fathers of hospitalized premature infants. PRINCIPAL RESULTS: Fathers described 3
      types of behaviors used to support the provision of breast milk to their
      hospitalized premature infants: assistance with the pumping process, assumption
      of additional daily domestic responsibilities, and provision of moral support.
      CONCLUSIONS: Results from this study suggest several significant behaviors that
      fathers perceived they performed to support their partners' efforts to provide
      breast milk to their hospitalized premature infants.

PMID- 17208164
TI  - A descriptive study of mothers' experiences feeding their preterm infants after
      discharge.
AB  - PURPOSE: The purpose of this study was to explore mothers' perceptions of their
      experiences in feeding their preterm infants in the early weeks after hospital
      discharge. SUBJECTS: Twenty-seven mothers whose preterm infants were part of a
      larger study of feeding readiness participated. DESIGN: A qualitative,
      descriptive approach was used to explore mothers' experiences in feeding their
      preterm infants after hospital discharge. METHODS: A convenience sample of
      mothers of preterm infants were interviewed 2 to 3 weeks after hospital
      discharge. Data were generated by semi-structured interview and analyzed by
      searching for thematic patterns in the data. Mothers were asked to describe their
      experiences feeding their infants, their perceptions of how their infants'
      feeding ability had changed since discharge, and the meanings they gave to these
      changes. The interviews were audiotaped and transcribed. Agreement of themes
      between the investigators was achieved. MAIN OUTCOME MEASURES: Three themes
      emerged from the interviews: interpreting infant behaviors, managing the feeding
      process, and realizing knowledge gaps. PRINCIPAL RESULTS: Mothers struggle with
      infant feeding in the first few weeks after discharge and experience a period of
      transition before comfort develops. CONCLUSIONS: Nursing interventions should
      include anticipatory guidance to mothers about feeding their infants after
      discharge and more concrete information regarding infant cues of hunger and
      satiation. Follow-up visits after discharge should include a review of the
      current feeding regimen, information regarding feeding progression, and
      reinforcement about changing infant behaviors as the preterm infant approaches 40
      weeks postmenstrual age.

PMID- 17208167
TI  - Saving endangered whales at no cost.

PMID- 17208168
TI  - Radiation resistance: resurrection by recombination.
AB  - Adaptation to extreme desiccation has conferred extraordinary radiation
      resistance on the bacterium Deinococcus radiodurans. How this organism is able to
      reconstruct a genome shattered by gamma rays has now been revealed.

PMID- 17208169
TI  - Human populations: houses for spouses.
AB  - Patterns of genetic variability in human populations are profoundly influenced by
      social organisation, including lifestyle, language, religion and social status. A
      nice illustration is seen among societies that have specific rules about who can
      marry whom.

PMID- 17208170
TI  - Global warming: fly populations are responding rapidly to climate change.
AB  - New studies on chromosome inversion polymorphisms in Drosophila species show that
      the genetic constitution of populations is responding to recent climate change
      and that widespread species may have the potential to undergo adaptive shifts.
      Genetic markers in widespread species can act as indicators of climate change on
      natural populations.

PMID- 17208171
TI  - Microtubule modification: acetylation speeds anterograde traffic flow.
AB  - Microtubules in neurites undergo multiple post-translational modifications.
      Recent work shows that neurites enriched in acetylated microtubules selectively
      support kinesin-mediated transport of the JNK regulator JIP-1 to growth cones.

PMID- 17208172
TI  - Visual neuroscience: face-encoding mechanisms revealed by adaptation.
AB  - Faces convey a great variety of information, for example about the species,
      gender, age, identity and even mood or intentions. A recent study sheds light on
      the neural mechanisms for encoding a face's gaze direction.

PMID- 17208173
TI  - Drosophila immunity: is antigen processing the first step?
AB  - A new genetic study has shown that the phagocytic ability of Drosophila blood
      cells, the hemocytes, may be important for the further induction of an
      antibacterial response in other tissues.

PMID- 17208174
TI  - Cell adhesion: separation of p120's powers?
AB  - The catenin p120 is involved in many processes, including cell-cell adhesion and
      cancer. Recent work explores whether p120 independently regulates two key binding
      partners, RhoGTPase and cadherin.

PMID- 17208175
TI  - Ecology: a different route to recovery for coral reefs.
AB  - Worldwide, many coral reef ecosystems have undergone regime shifts, changing from
      domination by coral to domination by algae. New work indicates that the return
      path is surprisingly different from the forward one.

PMID- 17208176
TI  - Rapid conduction and the evolution of giant axons and myelinated fibers.
AB  - Nervous systems have evolved two basic mechanisms for increasing the conduction
      speed of the electrical impulse. The first is through axon gigantism: using axons
      several times larger in diameter than the norm for other large axons, as for
      example in the well-known case of the squid giant axon. The second is through
      encasing axons in helical or concentrically wrapped multilamellar sheets of
      insulating plasma membrane--the myelin sheath. Each mechanism, alone or in
      combination, is employed in nervous systems of many taxa, both vertebrate and
      invertebrate. Myelin is a unique way to increase conduction speeds along axons of
      relatively small caliber. It seems to have arisen independently in evolution
      several times in vertebrates, annelids and crustacea. Myelinated nerves,
      regardless of their source, have in common a multilamellar membrane wrapping, and
      long myelinated segments interspersed with 'nodal' loci where the myelin
      terminates and the nerve impulse propagates along the axon by 'saltatory'
      conduction. For all of the differences in detail among the morphologies and
      biochemistries of the sheath in the different myelinated animal classes, the
      function is remarkably universal.

PMID- 17208177
TI  - Prosopagnosia.

PMID- 17208178
TI  - Mediaeval artists: masters in directing the observers' gaze.

PMID- 17208179
TI  - Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic
      cell death.
AB  - BACKGROUND: To survive starvation and other forms of stress, eukaryotic cells
      undergo a lysosomal process of cytoplasmic degradation known as autophagy.
      Autophagy has been implicated in a number of cellular and developmental
      processes, including cell-growth control and programmed cell death. However,
      direct evidence of a causal role for autophagy in these processes is lacking,
      resulting in part from the pleiotropic effects of signaling molecules such as TOR
      that regulate autophagy. Here, we circumvent this difficulty by directly
      manipulating autophagy rates in Drosophila through the autophagy-specific protein
      kinase Atg1. RESULTS: We find that overexpression of Atg1 is sufficient to induce
      high levels of autophagy, the first such demonstration among wild-type Atg
      proteins. In contrast to findings in yeast, induction of autophagy by Atg1 is
      dependent on its kinase activity. We find that cells with high levels of Atg1
      induced autophagy are rapidly eliminated, demonstrating that autophagy is capable
      of inducing cell death. However, this cell death is caspase dependent and
      displays DNA fragmentation, suggesting that autophagy represents an alternative
      induction of apoptosis, rather than a distinct form of cell death. In addition,
      we demonstrate that Atg1-induced autophagy strongly inhibits cell growth and that
      Atg1 mutant cells have a relative growth advantage under conditions of reduced
      TOR signaling. Finally, we show that Atg1 expression results in negative feedback
      on the activity of TOR itself. CONCLUSIONS: Our results reveal a central role for
      Atg1 in mounting a coordinated autophagic response and demonstrate that autophagy
      has the capacity to induce cell death. Furthermore, this work identifies
      autophagy as a critical mechanism by which inhibition of TOR signaling leads to
      reduced cell growth.

PMID- 17208180
TI  - The chemotactic behavior of computer-based surrogate bacteria.
AB  - BACKGROUND: Chemotaxis is the process by which organisms migrate toward nutrients
      and favorable environments and away from toxins and unfavorable environments. In
      many species of bacteria, this occurs when extracellular signals are detected by
      transmembrane receptors and relayed to flagellar motors, which control the cell's
      swimming behavior. RESULTS: We used a molecularly detailed reaction-kinetics
      model of the chemotaxis pathway in Escherichia coli coupled to a graphical
      display based on known swimming parameters to simulate the responses of bacteria
      to 2D gradients of attractants. The program gives the correct phenotype of over
      60 mutants in which chemotaxis-pathway components are deleted or overexpressed
      and accurately reproduces the responses to pulses and step increases of
      attractant. In order to match the known sensitivity of bacteria to low
      concentrations of attractant, we had to introduce a set of "infectivity"
      reactions based on cooperative interactions between neighboring chemotaxis
      receptors in the membrane. In order to match the impulse response to a brief
      stimulus and to achieve an effective accumulation in a gradient, we also had to
      increase the activities of the adaptational enzymes CheR and CheB at least an
      order of magnitude greater than published values. Our simulations reveal that
      cells develop characteristic levels of receptor methylation and swimming behavior
      at different positions along a gradient. They also predict a distinctive
      "volcano" profile in some gradients, with peaks of cell density at intermediate
      concentrations of attractant. CONCLUSIONS: Our results display the potential use
      of computer-based bacteria as experimental objects for exploring subtleties of
      chemotactic behavior.

PMID- 17208182
TI  - Interference with bottom-up feature detection by higher-level object recognition.
AB  - Drawing portraits upside down is a trick that allows novice artists to reproduce
      lower-level image features, e.g., contours, while reducing interference from
      higher-level face cognition. Limiting the available processing time to suffice
      for lower- but not higher-level operations is a more general way of reducing
      interference. We elucidate this interference in a novel visual-search task to
      find a target among distractors. The target had a unique lower-level orientation
      feature but was identical to distractors in its higher-level object shape.
      Through bottom-up processes, the unique feature attracted gaze to the target.
      Subsequently, recognizing the attended object as identically shaped as the
      distractors, viewpoint invariant object recognition interfered. Consequently,
      gaze often abandoned the target to search elsewhere. If the search stimulus was
      extinguished at time T after the gaze arrived at the target, reports of target
      location were more accurate for shorter (T<500 ms) presentations. This object-to
      feature interference, though perhaps unexpected, could underlie common phenomena
      such as the visual-search asymmetry that finding a familiar letter N among its
      mirror images is more difficult than the converse. Our results should enable
      additional examination of known phenomena and interactions between different
      levels of visual processes.

PMID- 17208181
TI  - Separate coding of different gaze directions in the superior temporal sulcus and
      inferior parietal lobule.
AB  - Electrophysiological recording in the anterior superior temporal sulcus (STS) of
      monkeys has demonstrated separate cell populations responsive to direct and
      averted gaze. Human functional imaging has demonstrated posterior STS activation
      in gaze processing, particularly in coding the intentions conveyed by gaze, but
      to date has provided no evidence of dissociable coding of different gaze
      directions. Because the spatial resolution typical of group-based fMRI studies
      (approximately 6-10 mm) exceeds the size of cellular patches sensitive to
      different facial characteristics (1-4 mm in monkeys), a more sensitive technique
      may be required. We therefore used fMRI adaptation, which is considered to offer
      superior resolution, to investigate whether the human anterior STS contains
      representations of different gaze directions, as suggested by non-human primate
      research. Subjects viewed probe faces gazing left, directly ahead, or right.
      Adapting to leftward gaze produced a reduction in BOLD response to left relative
      to right (and direct) gaze probes in the anterior STS and inferior parietal
      cortex; rightward gaze adaptation produced a corresponding reduction to right
      gaze probes. Consistent with these findings, averted gaze in the adapted
      direction was misidentified as direct. Our study provides the first human
      evidence of dissociable neural systems for left and right gaze.

PMID- 17208183
TI  - Paternal indirect genetic effects on offspring viability and the benefits of
      polyandry.
AB  - Although females are expected to maximize their reproductive success with only
      one or a few matings, the females of many species mate with multiple partners.
      Experimental studies have found evidence for an increase in egg or embryo
      viability when females mate polyandrously. These studies have been interpreted in
      the context of genetic-benefit models that propose that multiple mating increases
      offspring viability because it allows females to select male genotypes that
      influence viability directly or because it allows females to avoid genetic
      incompatibility. However, no studies have examined directly the precise
      mechanisms by which parents influence embryo viability. Using a morphological
      marker that enabled us to determine paternity and survival of embryos sired by
      individual male crickets in both sperm-competitive and -noncompetitive
      situations, we show that males inducing high embryo viability enhance the
      viability of embryos sired by inferior males. These results indicate that
      paternal effects and interacting phenotypes determine embryo viability. They show
      that a male's reproductive success is modified by the interaction between
      indirect genetic effects of sperm competitors. Importantly, our findings show
      that the benefits accruing to offspring of multiply mated females need not be
      transmitted genetically.

PMID- 17208184
TI  - Experience-driven axon retraction without binocular imbalance in developing
      visual cortex.
AB  - Refinement of the neural circuit during brain maturation is regulated by
      experience-driven neural activity. In the mammalian visual cortex, monocular
      visual deprivation (MD) in the early postnatal life causes a significant loss of
      cortical responses to a deprived eye and the retraction of input axons serving
      the deprived eye. A competitive interaction between inputs serving both eyes has
      been supposed to underlie the effects of MD because the loss of cortical response
      is much weaker when both eyes are deprived of vision. Also, the input axons do
      not retract after binocular deprivation. Here, we report that uncorrelated
      activity between presynaptic and postsynaptic neurons can solely lead to the
      retraction of geniculocortical axons in the absence of activity imbalance between
      two inputs. We analyzed the morphology of geniculocortical axons in a
      pharmacologically inhibited visual cortex of animals with normal vision and of
      binocularly deprived animals. In the normal vision animals, the axonal arbors in
      the inhibited cortex showed robust retraction. On the other hand, the arbors in
      binocularly deprived animals remained mostly intact. These results suggest that a
      homosynaptic associative mechanism, rather than a heterosynaptic competition
      between inputs, may play an important role in experience-driven axon retraction.

PMID- 17208185
TI  - From social to genetic structures in central Asia.
AB  - Pastoral and farmer populations, who have coexisted in Central Asia since the
      fourth millennium B.C., present not only different lifestyles and means of
      subsistence but also various types of social organization. Pastoral populations
      are organized into so-called descent groups (tribes, clans, and lineages) and
      practice exogamous marriages (a man chooses a bride in a different lineage or
      clan). In Central Asia, these descent groups are patrilineal: The children are
      systematically affiliated with the descent groups of the father. By contrast,
      farmer populations are organized into families (extended or nuclear) and often
      establish endogamous marriages with cousins. This study aims at better
      understanding the impact of these differences in lifestyle and social
      organization on the shaping of genetic diversity. We show that pastoral
      populations exhibit a substantial loss of Y chromosome diversity in comparison to
      farmers but that no such a difference is observed at the mitochondrial-DNA level.
      Our analyses indicate that the dynamics of patrilineal descent groups, which
      implies different male and female sociodemographic histories, is responsible for
      these sexually-asymmetric genetic patterns. This molecular signature of the
      pastoral social organization disappears over a few centuries only after
      conversion to an agricultural way of life.

PMID- 17208186
TI  - Temporal discounting predicts risk sensitivity in rhesus macaques.
AB  - Humans and animals tend both to avoid uncertainty and to prefer immediate over
      future rewards. The comorbidity of psychiatric disorders such as impulsivity,
      problem gambling, and addiction suggests that a common mechanism may underlie
      risk sensitivity and temporal discounting. Nonetheless, the precise relationship
      between these two traits remains largely unknown. To examine whether risk
      sensitivity and temporal discounting reflect a common process, we recorded
      choices made by two rhesus macaques in a visual gambling task while we varied the
      delay between trials. We found that preference for the risky option declined with
      increasing delay between sequential choices in the task, even when all other task
      parameters were held constant. These results were quantitatively predicted by a
      model that assumed that the subjective expected utility of the risky option is
      evaluated based on the expected time of the larger payoff. The importance of the
      larger payoff in this model suggests that the salience of larger payoffs played a
      critical role in determining the value of risky options. These data suggest that
      risk sensitivity may be a product of other cognitive processes, and specifically
      that myopia for the future and the salience of jackpots control the propensity to
      take a gamble.

PMID- 17208187
TI  - The DNA glycosylase/lyase ROS1 functions in pruning DNA methylation patterns in
      Arabidopsis.
AB  - The Arabidopsis DNA glycosylase/lyase ROS1 participates in active DNA
      demethylation by a base-excision pathway. ROS1 has been shown to be required for
      demethylating a transgene promoter. To determine the function of ROS1 in
      demethylating endogenous loci, we carried out bisulfite-sequencing analysis of
      several transposons and other genes in the ros1 mutant. In the wild-type,
      although CpG sites at the majority of these loci are heavily methylated, many of
      the CpXpG and CpXpX sites have low levels of methylation or are not at all
      methylated. However, these CpXpG and CpXpX sites become heavily methylated in the
      ros1 mutant. Associated with this increased DNA methylation, these loci show
      decreased expression in the ros1 mutant. Our results suggest that active DNA
      demethylation is important in pruning the methylation patterns of the genome, and
      even the normally "silent" transposons are under dynamic control by both
      methylation and demethylation. This dynamic control may be important in keeping
      the plant epigenome plastic so that it can efficiently respond to developmental
      and environmental cues.

PMID- 17208188
TI  - Cilia-driven leftward flow determines laterality in Xenopus.
AB  - Determination of the vertebrate left-right body axis during embryogenesis results
      in asymmetric development and placement of most inner organs. Although the
      asymmetric Nodal cascade is conserved in all vertebrates, the mechanism of
      symmetry breakage has remained controversial. In mammalian and fish embryos, a
      cilia-driven leftward flow of extracellular fluid is required for initiation of
      the Nodal cascade. This flow is localized at the posterior notochord ("node") and
      Kupffer's vesicle, respectively. In frog and chick embryos, however, molecular
      asymmetries are required earlier, from cleavage stages through gastrulation. The
      validity of a cilia-based mechanism for all vertebrates therefore has been
      questioned. Here we show that a cilia-driven leftward flow precedes asymmetric
      nodal expression in the frog Xenopus. Motile monocilia emerged on the gastrocoel
      roof plate during neurulation and lengthened and polarized from an initially
      central position to the posterior pole of cells. Concomitantly, a robust leftward
      fluid flow developed from stage 15 onward, significantly before asymmetric nodal
      transcription started in the left-lateral-plate mesoderm at stage 19. Injection
      of 1.5% methylcellulose into the archenteron prevented leftward flow and resulted
      in laterality defects, demonstrating that the flow itself was required for
      asymmetric gene expression and organ placement.

PMID- 17208189
TI  - Psidin is required in Drosophila blood cells for both phagocytic degradation and
      immune activation of the fat body.
AB  - Phagocytic blood cells are critical to innate immune defense: They internalize
      and destroy microbial invaders and produce signals that trigger other immune
      responses. Despite this central role, the in vivo contributions of phagocytosis
      to systemic immune activation are not well understood. Drosophila has proven a
      fruitful model for the investigation of evolutionarily conserved innate immune
      mechanisms, including NF-kappaB-dependent transcriptional induction, RNAi in
      antiviral responses, and phagocytosis. The phagocytes of Drosophila encounter
      bacterial invaders early in infection and contribute to survival of infection.
      Phagocytosis in flies and mammals is highly homologous: Both rely on scavenger
      receptors, opsonins, and actin rearrangements for engulfment; have phagosomal
      cysteine proteases active at low pH; and can be subverted by similar
      intracellular pathogens. Although the role of Drosophila phagocytes in the
      activation of other immune tissues has not been clear, we show that induction of
      the antibacterial-peptide gene Defensin in the fat body during infection requires
      blood-cell contributions. We identify a gene, psidin, that encodes a lysosomal
      protein required in the blood cells for both degradation of engulfed bacteria and
      activation of fat-body Defensin. These data establish a role for the phagocytic
      blood cells of Drosophila in detection of infection and activation of the humoral
      immune response.

PMID- 17208190
TI  - Organization of actin networks in intact filopodia.
AB  - Filopodia are finger-like extensions of the cell surface that are involved in
      sensing the environment, in attachment of particles for phagocytosis, in
      anchorage of cells on a substratum, and in the response to chemoattractants or
      other guidance cues. Filopodia present an excellent model for actin-driven
      membrane protrusion. They grow at their tips by the assembly of actin and are
      stabilized along their length by a core of bundled actin filaments. To visualize
      actin networks in their native membrane-anchored state, filopodia of
      Dictyostelium cells were subjected to cryo-electron tomography. At the site of
      actin polymerization, a peculiar structure, the "terminal cone," is built of
      short filaments fixed with their distal end to the filopod's tip and with their
      proximal end to the flank of the filopod. The backbone of the filopodia consists
      of actin filaments that are shorter than the entire filopod and aligned in
      parallel or obliquely to the filopod's axis. We hypothesize that growth of the
      highly dynamic filopodia of Dictyostelium is accompanied by repetitive nucleation
      of actin polymerization at the filopod tip, followed by the rearrangement of
      filaments within the shaft.

PMID- 17208192
TI  - Progress in characterization of Langmuir monolayers by consideration of
      compressibility.
AB  - Over decades, information about the rheological properties of the condensed
      monolayer phases has been obtained by introduction of a two-dimensional
      compressibility which is defined on the basis of the surface pressure-molecular
      area (Pi-A) features of the monolayer. Since the last decade, fundamental
      progress was attained in the experimental determination of the main
      characteristics of Langmuir monolayers in microscopic and molecular scale.
      Already smallest changes in the molecular structure of the amphiphile can result
      in changes in the molecular arrangement in the monolayer and thus, in changes of
      the main characteristics of the monolayer such as, the surface pressure-area per
      molecule (Pi-A) isotherms, the shape and texture of the condensed phase domains
      and the two-dimensional lattice structure. As the classical equations of state
      allowed only characterisation of the fluid (gaseous, liquid-expanded) state,
      thermodynamically based equations of state, which consider also the aggregation
      of the monolayer material to the condensed phase, have been developed. The
      present review focuses particularly to amphiphilic monolayers, the Pi-A isotherms
      of which indicate the existence of two condensed phases. For this case, the
      experimental results of the differences in the structure features and phase
      properties are discussed. The generalisation of the equation of state for
      Langmuir monolayers developed for the case that one, two or more phase
      transitions in the monolayer take place, is in agreement with the experimental
      results that the two-dimensional compressibility of the condensed phases
      undergoes a jump at the phase transition, whereas the compressibility is
      proportional to the surface pressure within one of the condensed phases. An
      example is presented which explains the procedure of the theoretical analysis of
      Pi-A isotherms indicating the existence of two condensed phases. An element of
      the procedure is the application of the general principle that the behaviour of
      any thermodynamic system is determined by the stability condition. An interesting
      anisotropy of the compressibility is revealed by GIXD studies of the S-phase of
      octadecanol monolayers. However, similar studies performed close to the LS-S
      phase transition would result in a thermodynamically impossible negative
      compressibility. Close to this phase transition, the compressibility cannot be
      determined from the positions of the maxima because the monolayer is in a
      disordered state attributed to elastic distortions by fluctuations with the
      structure of the new phase in the surrounding matrix without destroying the quasi
      long-range positional order.

PMID- 17208191
TI  - Cyclin A2 regulates nuclear-envelope breakdown and the nuclear accumulation of
      cyclin B1.
AB  - Mitosis is thought to be triggered by the activation of Cdk-cyclin complexes.
      Here we have used RNA interference (RNAi) to assess the roles of three mitotic
      cyclins, cyclins A2, B1, and B2, in the regulation of centrosome separation and
      nuclear-envelope breakdown (NEB) in HeLa cells. We found that the timing of NEB
      was affected very little by knocking down cyclins B1 and B2 alone or in
      combination. However, knocking down cyclin A2 markedly delayed NEB, and knocking
      down both cyclins A2 and B1 delayed NEB further. The timing of cyclin B1-Cdk1
      activation was normal in cyclin A2 knockdown cells, and there was no delay in
      centrosome separation, an event apparently controlled by the activation of
      cytoplasmic cyclin B1-Cdk1. However, nuclear accumulation of cyclin B1-Cdk1 was
      markedly delayed in cyclin A2 knockdown cells. Finally, a constitutively nuclear
      cyclin B1, but not wild-type cyclin B1, restored normal NEB timing in cyclin A2
      knockdown cells. These findings show that cyclin A2 is required for timely NEB,
      whereas cyclins B1 and B2 are not. Nevertheless cyclin B1 translocates to the
      nucleus just prior to NEB in a cyclin A2-dependent fashion and is capable of
      supporting NEB if rendered constitutively nuclear.

PMID- 17208193
TI  - The role of Sdh4p Tyr-89 in ubiquinone reduction by the Saccharomyces cerevisiae
      succinate dehydrogenase.
AB  - Succinate dehydrogenase (complex II or succinate:ubiquinone oxidoreductase) is a
      tetrameric, membrane-bound enzyme that catalyzes the oxidation of succinate and
      the reduction of ubiquinone in the mitochondrial respiratory chain. Two electrons
      from succinate are transferred one at a time through a flavin cofactor and a
      chain of iron-sulfur clusters to reduce ubiquinone to an ubisemiquinone
      intermediate and to ubiquinol. Residues that form the proximal quinone-binding
      site (Q(P)) must recognize ubiquinone, stabilize the ubisemiquinone intermediate,
      and protonate the ubiquinone to ubiquinol, while minimizing the production of
      reactive oxygen species. We have investigated the role of the yeast Sdh4p Tyr-89,
      which forms a hydrogen bond with ubiquinone in the Q(P) site. This tyrosine
      residue is conserved in all succinate:ubiquinone oxidoreductases studied to date.
      In the human SDH, mutation of this tyrosine to cysteine results in paraganglioma,
      tumors of the parasympathetic ganglia in the head and neck. We demonstrate that
      Tyr-89 is essential for ubiquinone reductase activity and that mutation of Tyr-89
      to other residues does not increase the production of reactive oxygen species.
      Our results support a role for Tyr-89 in the protonation of ubiquinone and argue
      that the generation of reactive oxygen species is not causative of tumor
      formation.

PMID- 17208194
TI  - The role of the FtsH and Deg proteases in the repair of UV-B radiation-damaged
      Photosystem II in the cyanobacterium Synechocystis PCC 6803.
AB  - The photosystem two (PSII) complex found in oxygenic photosynthetic organisms is
      susceptible to damage by UV-B irradiation and undergoes repair in vivo to
      maintain activity. Until now there has been little information on the identity of
      the enzymes involved in repair. In the present study we have investigated the
      involvement of the FtsH and Deg protease families in the degradation of UV-B
      damaged PSII reaction center subunits, D1 and D2, in the cyanobacterium
      Synechocystis 6803. PSII activity in a DeltaFtsH (slr0228) strain, with an
      inactivated slr0228 gene, showed increased sensitivity to UV-B radiation and
      impaired recovery of activity in visible light after UV-B exposure. In contrast,
      in DeltaDeg-G cells, in which all the three deg genes were inactivated, the
      damage and recovery kinetics were the same as in the WT. Immunoblotting showed
      that the loss of both the D1 and D2 proteins was retarded in DeltaFtsH (slr0228)
      during UV-B exposure, and the extent of their restoration during the recovery
      period was decreased relative to the WT. However, in the DeltaDeg-G cells the
      damage and recovery kinetics of D1 and D2 were the same as in the WT. These data
      demonstrate a key role of FtsH (slr0228), but not the Deg proteases, for the
      repair of PS II during and following UV-B radiation at the step of degrading both
      of the UV-B damaged D1 and D2 reaction center subunits.

PMID- 17208195
TI  - Structural correlates of antimicrobial efficacy in IL-8 and related human
      kinocidins.
AB  - Chemokines are small (8-12 kDa) effector proteins that potentiate leukocyte
      chemonavigation. Beyond this role, certain chemokines have direct antimicrobial
      activity against human pathogenic organisms; such molecules are termed
      kinocidins. The current investigation was designed to explore the structure
      activity basis for direct microbicidal activity of kinocidins. Amino acid
      sequence and 3-dimensional analyses demonstrated these molecules to contain
      iterations of the conserved gamma-core motif found in broad classes of classical
      antimicrobial peptides. Representative CXC, CC and C cysteine-motif-group
      kinocidins were tested for antimicrobial activity versus human pathogenic
      bacteria and fungi. Results demonstrate that these molecules exert direct
      antimicrobial activity in vitro, including antibacterial activity of native IL-8
      and MCP-1, and microbicidal activity of native IL-8. To define molecular
      determinants governing its antimicrobial activities, the IL-8 gamma-core (IL
      8gamma) and alpha-helical (IL-8alpha) motifs were compared to native IL-8 for
      antimicrobial efficacy in vitro. Microbicidal activity recapitulating that of
      native IL-8 localized to the autonomous IL-8alpha motif in vitro, and
      demonstrated durable microbicidal activity in human blood and blood matrices ex
      vivo. These results offer new insights into the modular architecture, context
      related deployment and function, and evolution of host defense molecules
      containing gamma-core motifs and microbicidal helices associated with
      antimicrobial activity.

PMID- 17208196
TI  - Coencapsulation of irinotecan and floxuridine into low cholesterol-containing
      liposomes that coordinate drug release in vivo.
AB  - A liposomal delivery system that coordinates the release of irinotecan and
      floxuridine in vivo has been developed. The encapsulation of floxuridine was
      achieved through passive entrapment while irinotecan was actively loaded using a
      novel copper gluconate/triethanolamine based procedure. Coordinating the release
      rates of both drugs was achieved by altering the cholesterol content of
      distearoylphosphatidylcholine (DSPC)/distearoylphosphatidylglycerol (DSPG) based
      formulations. The liposomal retention of floxuridine in plasma after intravenous
      injection was dramatically improved by decreasing the cholesterol content of the
      formulation below 20 mol%. In the case of irinotecan, the opposite trend was
      observed where increasing cholesterol content enhanced drug retention. Liposomes
      composed of DSPC/DSPG/Chol (7:2:1, mole ratio) containing co-encapsulated
      irinotecan and floxuridine at a 1:1 molar ratio exhibited matched leakage rates
      for the two agents so that the 1:1 ratio was maintained after intravenous
      administration to mice. The encapsulation of irinotecan was optimal when copper
      gluconate/triethanolamine (pH 7.4) was used as the intraliposomal buffer. The
      efficiency of irinotecan loading was approximately 80% with a starting drug to
      lipid molar ratio of 0.1/1. Leakage of floxuridine from the liposomes during
      irinotecan loading at 50 degrees C complicated the ability to readily achieve the
      target 1:1 irinotecan/floxuridine ratio inside the formulation. As a result, a
      procedure for the simultaneous encapsulation of irinotecan and floxuridine was
      developed. This co-encapsulation method has the advantage over sequential loading
      in that extrusion can be performed in the absence of chemotherapeutic agents and
      the drug/drug ratios in the final formulation can be more precisely controlled.

PMID- 17208197
TI  - Clinical obsessions in obsessive-compulsive patients and obsession-relevant
      intrusive thoughts in non-clinical, depressed and anxious subjects: where are the
      differences?
AB  - Contemporary cognitive models of obsessive-compulsive disorder (OCD) assume that
      clinical obsessions evolve from some modalities of intrusive thoughts (ITs) that
      are experienced by the vast majority of the population. These approaches also
      consider that the differences between "abnormal" obsessions and "normal" ITs rely
      on quantitative parameters rather than qualitative. The present paper examines
      the frequency, contents, emotional impact, consequences, cognitive appraisals and
      control strategies associated with clinical obsessions in a group of 31 OCD
      patients compared with the obsession-relevant ITs in three control groups: 22
      depressed patients, 31 non-obsessive anxious patients, and 30 non-clinical
      community subjects. Between-group differences indicated that the ITs frequency,
      the unpleasantness and uncontrollability of having the IT, and the avoidance of
      thought triggers obtained the highest effect sizes, and they were specific to OCD
      patients. Moreover, two dysfunctional appraisals (worry that the thought will
      come true, and the importance of controlling thoughts) were specific to OCD
      patients. The OCD and depressed patients shared some dysfunctional appraisals
      about their most disturbing obsession or IT (guilt, unacceptability, likelihood
      thought would come true, danger, and responsibility for having the IT), whereas
      the non-obsessive anxious were nearer to the non-clinical participants than to
      the other two groups of patients. The OCD patients showed an increased use of
      thought control strategies, with overt neutralizing, thought suppression, and
      searching for reassurance being highly specific to this group.

PMID- 17208198
TI  - Attentive processing of threat and adult attachment: a dot-probe study.
AB  - We examined selective attention to threat stimuli as a function of individual
      differences in adult attachment. Participants completed a dot-probe task in which
      a general threat word, attachment-related threat word, general positive or
      attachment-related positive word was presented together with a neutral word.
      Results showed that attachment anxiety and avoidance were associated with an
      attentional bias away from attachment threat words. This attentional avoidance
      effect was best predicted by the interaction between attachment anxiety and
      avoidance and not by their unique main effects. The findings are discussed in
      terms of attachment theory and its relation to attentional biases observed in
      psychopathology.

PMID- 17208199
TI  - Predicting short-term outcome in well-being following suicidal behaviour: the
      conjoint effects of social perfectionism and positive future thinking.
AB  - This study investigated an integrative, psychological model of suicidality
      involving the relationship between perfectionism and future thinking to predict
      short-term outcome in well-being following a suicidal episode. Two hundred and
      sixty-seven adults hospitalized following a self-harm episode completed a range
      of clinical and psychological measures in hospital and were followed up
      approximately two months after discharge. Hierarchical regression analyses
      confirmed that, among the suicidal self-harmers who had a history of repetitive
      self-harm (n=65), outcome among low social perfectionists changed as a function
      of positive future thinking such that outcome was better for those high on
      positive thoughts compared with those low on positive future thoughts. There was
      no such positive change in outcome among the high social perfectionists. There
      were also no significant interactive effects evident among the non-repetitive
      self-harmers (n=61). These findings extend recent research to suggest that
      socially prescribed perfectionism and positive future thinking (but not negative
      future thinking) are implicated in outcome following repetitive suicidality.
      Implications for theory and clinical practice are discussed.

PMID- 17208200
TI  - Digeranyl bisphosphonate inhibits geranylgeranyl pyrophosphate synthase.
AB  - A primary cellular target of the clinical nitrogenous bisphosphonates is the
      isoprenoid biosynthetic pathway. Specifically these drugs inhibit the enzyme
      farnesyl pyrophosphate synthase and deplete cells of larger isoprenoids.
      Inhibition of this enzyme results in impaired processing of both farnesylated and
      geranylgeranylated proteins. We recently showed that isoprenoid-containing
      bisphosphonates such as digeranyl bisphosphonate inhibit protein
      geranylgeranylation and not farnesylation. Here, we show that this impairment
      results from potent and specific inhibition of geranylgeranyl pyrophosphate
      synthase, which leads to enhanced depletion of intracellular geranylgeranyl
      pyrophosphate relative to the nitrogenous bisphosphonate zoledronate.

PMID- 17208201
TI  - Aggregate-centered redistribution of proteins by mutant huntingtin.
AB  - Huntingtin is a widely expressed 350-kDa cytosolic multidomain of unknown
      function. Aberrant expansion of the polyglutamine tract located in the N-terminal
      region of huntingtin results in Huntington's disease. The presence of insoluble
      huntingtin inclusions in the brains of patients is one of the hallmarks of
      Huntington's disease. Experimentally, both full-length huntingtin and N-terminal
      fragments of huntingtin with expanded polyglutamine tracts trigger aggregate
      formation. Here, we report that upon the formation of huntingtin aggregates;
      endogenous cytosolic huntingtin, Hsc70/Hsp70 (heat shock protein and cognate
      protein of 70kDa) and syntaxin 1A become aggregate-centered. This redistribution
      suggests that these proteins are eventually depleted and become unavailable for
      normal cellular function. These results indicate that the cellular targeting of
      several key proteins are altered in the presence of mutant huntingtin and suggest
      that aggregate depletion of these proteins may underlie, in part, the sequence of
      disease progression.

PMID- 17208202
TI  - Rabs 8A and 14 are targets of the insulin-regulated Rab-GAP AS160 regulating
      GLUT4 traffic in muscle cells.
AB  - Insulin causes translocation of glucose transporter GLUT4 to the membrane of
      muscle and fat cells, a process requiring Akt activation. The Rab GTPase
      activating protein (Rab-GAP) AS160 is inhibited upon phosphorylation by insulin
      activated Akt, thereby allowing GLUT4 translocation. Although several Rab
      proteins are detected on GLUT4 vesicles, the target Rabs of AS160 involved in the
      GLUT4 translocation have not been identified. We test whether Rabs 8A, 10, and 14
      (in vitro targets of AS160) rescue the inhibition of GLUT4 translocation caused
      by 'constitutively active' 4P-AS160 in L6 muscle cells. Coexpression of GFP
      tagged Rabs 8A or Rab14 with 4P-AS160 prevented the inhibition of GLUT4
      translocation imposed by 4P-AS160. GFP-tagged, constitutively active Rab8A also
      elicited this rescue. In contrast, neither wild-type nor constitutively active
      GFP-tagged Rab10 restored GLUT4 translocation. These results suggest that Rab8A
      and possibly Rab14 may be targets of AS160 leading to GLUT4 translocation in L6
      muscle cells.

PMID- 17208204
TI  - Pharmacological induction of heat shock protein exerts neuroprotective effects in
      experimental intracerebral hemorrhage.
AB  - Heat shock proteins (HSPs) are reported to reduce inflammation and apoptosis in a
      variety of brain insults. Geranylgeranylacetone (GGA), developed as an antiulcer
      in Japan, has been known to induce HSP70 and to exert cytoprotective effects. In
      this study, we investigated whether GGA, as a specific HSP inducer, exerts
      therapeutic effects in experimentally induced intracerebral hemorrhage (ICH). ICH
      was induced with male Sprague-Dawley rats via the collagenase infusion. GGA (800
      mg/kg) was administered via oral tube according to various schedules of
      treatment. The treatment with GGA, beginning before the induction of ICH and
      continuing until day 3, showed the reduction of brain water content and the
      increased level of HSP70 protein, as compared to the treatment with vehicle,
      although GGA started after the induction of ICH or administered as a single dose
      before ICH failed to up-regulate HSP70 and to reduce brain edema. The rats
      treated with GGA exhibited better functional recovery than those treated with
      vehicle. In the pre- and post- treatment group, inflammatory cells and cell death
      in the perihematomal regions were found to have been decreased. The treatment of
      GGA inhibited the mRNA expression of MMP-9, uPA, IL-6 and MIP-1, with concomitant
      increment of eNOS and phosphorylated STAT3 and Akt after ICH. We demonstrated
      that GGA induced a reduction in the brain edema along with marked inhibitory
      effects on inflammation and cell death after ICH.

PMID- 17208203
TI  - Cloning, expression, and characterization of an alternatively spliced variant of
      human heparanase.
AB  - Heparanase is an endoglycosidase that cleaves heparan sulfate in the
      extracellular matrix (ECM) and hence participates in ECM degradation and
      remodeling. Heparanase is involved in fundamental biological processes such as
      cancer metastasis, angiogenesis, and inflammation. Alternative splicing in the
      coding region of human heparanase was not reported. Here, we report the cloning
      of a splice variant of human heparanase that lacks exon 5 and is missing 174 bp
      compared to the wild-type cDNA. Splice 5 is expressed as a 55 kDa protein
      compared to the 65 and 50 kDa latent and active wild-type enzyme. Splice 5 was
      not detected in the incubation medium of tumor cells as opposed to the wild-type
      latent heparanase. Splice 5 escaped proteolytic cleavage, was devoid of HS
      degradation activity and exhibited diffused rather than granular cellular
      localization.

PMID- 17208205
TI  - Structure elucidation of arabinoxylan isomers by normal phase HPLC-MALDI-TOF/TOF
      MS/MS.
AB  - Normal phase-high performance liquid chromatography (NP-HPLC) coupled to matrix
      assisted laser desorption/ionization-time-of-flight/time-of-flight (MALDI
      TOF/TOF) tandem mass spectrometry is evaluated for the detailed structural
      characterization of various isomers of arabinoxylan (AX) oligosaccharides
      produced from endo-beta-(1-->4)-xylanase (endoxylanase) digestion of wheat AX.
      The fragmentation characteristics of these oligosaccharides upon MALDI-TOF/TOF
      high-energy collision induced dissociation (CID) were investigated using purified
      AX oligosaccharide standards labeled at the reducing end with 2-aminobenzoic acid
      (2-AA). A variety of cross-ring cleavages and 'elimination' ions in the fragment
      ion spectra provided extensive structural information, including Araf
      substitution patterns along the xylan backbone and comprehensive linkage
      assignment. The off-line coupling of this MALDI-CID technique to capillary normal
      phase HPLC enabled the separation and identification of isomeric oligosaccharides
      (DP 4-8) produced by endoxylanase digestion of AX. Furthermore, this technique
      was used to characterize structurally different isomeric AX oligosaccharides
      produced by endoxylanase enzymes with different substrate specificities.

PMID- 17208206
TI  - Stem cell-related cardiac gene expression early after murine myocardial
      infarction.
AB  - OBJECTIVE: Clinical experimental stem cell therapy after myocardial infarction
      appears feasible, but its use has preceded the understanding of the working
      mechanism. The ischemic recipient cardiac environment is determinative for the
      attraction and subsequent fate of stem cells. Here, we studied expression levels
      of genes that are anticipated to be essential for adequate stem cell-based
      cardiac repair at various time-points during the 1 month period following
      myocardial infarction (MI). METHODS: Gene expression in the hearts of mice that
      underwent MI by permanent or transient (30 min) ligation of the coronary artery
      was monitored using quantitative RT-PCR analysis of mRNA isolated from whole
      heart sections as well as from specific, laser micro-dissected, regions of
      sections. Protein expression was performed by immunohistochemical stainings and
      Western blot analysis. RESULTS: Many inflammatory genes were highly expressed for
      at least 1 week after MI. The expression of pro-angiogenic genes such as bFGF,
      VEGF-A and VEGF-R2 changed only marginally post-MI. Markers used to test stem
      cell gene expression remained unchanged post-MI with the exception of G-CSF and
      GM-CSF, which are genes that are also known to enhance the inflammatory response.
      Analysis of micro-dissected regions revealed that SDF-1, SCF (both stem cell
      attractants) and VEGF-R2 (involved in angiogenesis) gene expression was slightly
      decreased especially in the infarcted region. CONCLUSION: Genes that are
      generally considered to participate in stem cell-related processes and
      angiogenesis were not upregulated after MI, whereas the inflammatory gene
      expression dominated. Modulation of this imbalance might be of value for stem
      cell-mediated therapy.

PMID- 17208207
TI  - Pharmacological and physiological stimuli do not promote Ca(2+)-sensitive K+
      channel activity in isolated heart mitochondria.
AB  - OBJECTIVE: Mitochondrial calcium-activated K(+) (mitoK(Ca)) channels have been
      described as channels that are activated by Ca(2+), inner mitochondrial membrane
      depolarization and drugs such as NS-1619. NS-1619 is cardioprotective, leading to
      the assumption that this effect is related to the opening of mitoK(Ca) channels.
      Here, we show several weaknesses in this hypothesis. METHODS: Isolated
      mitochondria from rat hearts were tested for evidence of mitoK(Ca) activity by
      analyzing functional parameters in K(+)-rich and K(+)-free media. RESULTS: NS
      1619 promoted mitochondrial depolarization both in K(+)-rich and K(+)-free media.
      Respiratory rate increments were also seen in the presence of NS-1619 for both
      media. In parallel, NS-1619 promoted respiratory inhibition, as evidenced by
      respiratory measurements in state 3. Mitochondrial volume measurements conducted
      using light scattering showed that NS-1619 led to swelling, in a manner unaltered
      by inhibitors of mitoK(Ca) channels, antagonists of adenosine triphosphate
      sensitive potassium channels or inhibitors of the permeability transition.
      Swelling was also maintained when K(+) in the media was substituted with
      tetraethylammonium (TEA(+)), which is not transported by any known K(+) carrier.
      Electron microscopy experiments gave support to the idea that NS-1619-induced
      mitochondrial swelling took place in the absence of K(+). In addition to testing
      the pharmacological effects of NS-1619, we attempted, unsuccessfully, to promote
      mitoK(Ca) activity by altering Ca(2+) concentrations in the medium and inducing
      mitochondrial uncoupling. CONCLUSION: Our data indicate that NS-1619 promotes non
      selective permeabilization of the inner mitochondrial membrane to ions, in
      addition to partial respiratory inhibition. Furthermore, we found no specific
      K(+) transport in isolated heart mitochondria compatible with mitoK(Ca) opening,
      whether by pharmacological or physiological stimuli. Our results indicate that NS
      1619 has extensive mitochondrial effects unrelated to mitoK(Ca) and suggest that
      tissue protection mediated by NS-1619 may occur through mechanisms other than
      activation of these channels.

PMID- 17208208
TI  - The pivotal role of hepatocytes in drug discovery.
AB  - This review promotes the value of isolated hepatocytes in modern Drug Discovery
      programmes and outlines how increased understanding, particularly in the area of
      in vitro-in vivo extrapolation (IVIVE), has led to more widespread use. The
      importance of in vitro metabolic intrinsic clearance data for predicting in vivo
      clearance has been acknowledged for several years and the greater utility of
      hepatocytes, compared with hepatic microsomes and liver slices, for this
      application is discussed. The application of hepatocytes in predicting drug-drug
      interactions (DDIs) resulting from reversible and irreversible (time-dependent)
      inhibition is relatively novel but affords the potential to study both phase I
      and phase II processes together with any impact of drug efflux and/or uptake
      (cellular accumulation). Progress in this area is reviewed along with current
      opinions on the comparative use of primary hepatocytes and higher throughput
      reporter gene-based systems for studying cytochrome P450 (CYP) induction. The
      appreciation of the role of transporter proteins in drug disposition continues to
      evolve. The study of hepatic uptake using isolated hepatocytes and the interplay
      between drug transport and metabolism with respect to both clearance and DDIs and
      subsequent IVIVE is also considered.

PMID- 17208209
TI  - Tissue-polypeptide-specific antigen levels in diabetic patients with normal and
      pathological biochemical profiles.
AB  - OBJECTIVES: To identify causes for the raised TPS levels seen in diabetic
      patients. DESIGN AND METHODS: Relationships between TPS levels and biochemical
      markers for glycaemic control, hepatic dysfunction and renal dysfunction were
      investigated in 402 diabetic patients, none with evidence of cancer. RESULTS:
      Median TPS level (range) was 34.6 (19-276) U/L in controls versus 40.5 (16-691)
      U/L in type 1 diabetes mellitus (T1DM) patients and 53 (6-1654) U/L in type 2
      diabetes mellitus (T2DM) patients. TPS levels above the 95th percentile were
      observed in 26.1% diabetic patients and in 68.6% of these diabetic patients,
      raised TPS was associated with clinical complications or biochemical indicators
      of hepatic and/or renal dysfunction. CONCLUSIONS: The raised mean TPS levels seen
      in diabetic patients appear to be mainly due to the existence of hepatic or renal
      dysfunction.

PMID- 17208210
TI  - Cytokine promoter polymorphisms in Taiwanese patients with Graves' disease.
AB  - OBJECTIVES: This study aimed to examine the association between promoter
      polymorphisms of Th1 and Th2 cytokine genes [interleukin-4 (IL-4 T-34C, A-81G, C
      285T and T-589C), IL-6 (G-174C), IL-10 (A-592C and T-819C) and tumour necrosis
      factor-alpha (TNF-alpha G-238A and G-308A)] and Graves' disease (GD) in Taiwanese
      population. DESIGN AND METHODS: Genomic DNA was extracted from peripheral blood
      cells of 137 GD patients and 189 control subjects. Cytokine gene polymorphisms
      were analyzed by polymerase chain reaction and restriction fragment length
      polymorphism. RESULTS: Genotype frequencies of TNF-alpha G-238A or G-308A between
      control and GD subjects were significantly different. Frequencies of the high TNF
      alpha secreting alleles (-238*A and -308*A) and IL-10 -819*C allele were
      significantly increased in GD patients. No significant differences regarding IL-4
      or IL-6 gene polymorphisms between GD patients and control subjects were found.
      CONCLUSIONS: Our data demonstrated that TNF-alpha G-238A and G-308A genotypes
      were strongly associated with GD incidence.

PMID- 17208211
TI  - Measurement uncertainty of creatinine in low values: Another good reason not to
      use the MDRD formula with low creatinine values.

PMID- 17208212
TI  - Early oxidative stress in amniotic fluid of pregnancies with Down syndrome.
AB  - OBJECTIVE: Some evidence suggests that oxidative stress, due to an imbalance
      between oxidants and antioxidants, occurs in babies with Down syndrome (DS). This
      study tests the hypothesis that oxidative stress occurs early in DS pregnancies.
      DESIGN AND METHODS: Isoprostanes (IPs), a new marker of free radical-catalyzed
      lipid peroxidation, were measured in amniotic fluid from pregnancies with normal,
      growth restricted and DS fetuses, diagnosed by karyotype analysis of amniotic
      cells cultured. RESULTS: A nine-fold increase in IP concentrations was found in
      amniotic fluid of pregnancies with DS fetuses. This increase (595.15; 542.96
      631.64 pg/ml, median; 95% CI), was greater than in pregnancies with fetal growth
      restricted fetuses (155; 130.57-172.23 pg/ml, median; 95% CI) and normal fetuses
      (67; 49.82-98.38 pg/ml, median; 95% CI; p<0.0001). CONCLUSIONS: The study reveals
      that oxidative stress occurs early in pregnancy and supports the idea of testing
      whether prenatal antioxidant therapy may prevent or delay the onset of oxidative
      stress diseases in the DS population.

PMID- 17208213
TI  - Relationships between leptin, insulin, IGF-1 and IGFBP-3 in children with energy
      malnutrition.
AB  - OBJECTIVES: Leptin has a key role in energy homeostasis and there may be a link
      between leptin and insulin-like growth factor-1 (IGF-1) system. The aim of this
      study was to analyze the relationships between long-lasting insufficient caloric
      intake (marasmus), leptin and IGF-1 system. DESIGN AND METHODS: The study group
      consisted of 30 marasmic children and control group included 28 healthy children.
      After an overnight fasting; leptin, insulin, IGF-1 and IGFBP-3 levels were
      measured. RESULTS: Marasmic children had significantly lower body weight, height,
      mid-arm circumference (MAC), skinfold thickness, mean serum leptin, insulin, IGF
      1 and IGFBP-3 levels compared with healthy subjects (P<0.05). Serum IGF-1 and
      IGFBP-3 levels were significantly correlated with insulin, MAC and height Z score
      in patients (P<0.05). In controls, significant positive correlations were found
      between BMI, IGF-1 and leptin (P<0.05). CONCLUSIONS: Energy malnutrition is
      characterized by the important decreases in the leptin, insulin, IGF-1 and IGFBP
      3 levels. Understanding details of these changes may lead to new therapeutic
      approaches in disease states associated with malnutrition.

PMID- 17208214
TI  - One, two, three, four, nothing more: an investigation of the conceptual sources
      of the verbal counting principles.
AB  - Since the publication of [Gelman, R., & Gallistel, C. R. (1978). The child's
      understanding of number. Cambridge, MA: Harvard University Press.] seminal work
      on the development of verbal counting as a representation of number, the nature
      of the ontogenetic sources of the verbal counting principles has been intensely
      debated. The present experiments explore proposals according to which the verbal
      counting principles are acquired by mapping numerals in the count list onto
      systems of numerical representation for which there is evidence in infancy,
      namely, analog magnitudes, parallel individuation, and set-based quantification.
      By asking 3- and 4-year-olds to estimate the number of elements in sets without
      counting, we investigate whether the numerals that are assigned cardinal meaning
      as part of the acquisition process display the signatures of what we call
      "enriched parallel individuation" (which combines properties of parallel
      individuation and of set-based quantification) or analog magnitudes. Two
      experiments demonstrate that while "one" to "four" are mapped onto core
      representations of small sets prior to the acquisition of the counting
      principles, numerals beyond "four" are only mapped onto analog magnitudes about
      six months after the acquisition of the counting principles. Moreover, we show
      that children's numerical estimates of sets from 1 to 4 elements fail to show the
      signature of numeral use based on analog magnitudes - namely, scalar variability.
      We conclude that, while representations of small sets provided by parallel
      individuation, enriched by the resources of set-based quantification are
      recruited in the acquisition process to provide the first numerical meanings for
      "one" to "four", analog magnitudes play no role in this process.

PMID- 17208215
TI  - A two-stage method for MUAP classification based on EMG decomposition.
AB  - A method for the extraction and classification of individual motor unit action
      potentials (MUAPs) from needle electromyographic signals is presented. The
      proposed method automatically decomposes MUAPs and classifies them into normal,
      neuropathic or myopathic using a two-stage feature-based classifier. The method
      consists of four steps: (i) preprocessing of EMG recordings, (ii) MUAP clustering
      and detection of superimposed MUAPs, (iii) feature extraction and (iv) MUAP
      classification using a two-stage classifier. The proposed method employs Radial
      Basis Function Artificial Neural Networks and decision trees. It requires minimal
      use of tuned parameters and is able to provide interpretation for the
      classification decisions. The approach has been validated on real EMG recordings
      and an annotated collection of MUAPs. The success rate for MUAP clustering is
      96%, while the accuracy for MUAP classification is about 89%.

PMID- 17208216
TI  - Depletion of Med10 enhances Wnt and suppresses Nodal signaling during zebrafish
      embryogenesis.
AB  - The transcriptional Mediator (MED) is a multiprotein complex that transmits
      information from transcription factors to RNA polymerase II (PolII) to regulate
      transcription. At present, the role of distinct MED subunits in general
      transcription versus transcription stimulated by specific signaling pathways is
      unclear. By means of positional cloning, we reveal that the zebrafish mutant
      tennismatch is a hypomorphic allele of Med10, a conserved MED middle domain
      subunit. Using morpholino antisense oligonucleotides, we further demonstrate that
      reduction of Med10 levels led to an enhancement of the Wnt signaling pathway,
      while also suggesting a role for Med10 in mediating the Nodal signaling pathway.
      In contrast to the dual roles of Med10, reduction of Med12 and Med13 levels, two
      MED subunits in the regulatory domain, led to an enhancement of the Wnt signaling
      pathway but not the Nodal pathway, while reduction of Med15 levels, a MED subunit
      in the tail domain, suppressed the Nodal signaling pathway but not the Wnt
      signaling pathway. Thus, Med10 appears to be a unique MED subunit that
      differentially transduces information from distinct signaling pathways during
      zebrafish embryogenesis.

PMID- 17208217
TI  - Role of RhoC in digit morphogenesis during limb development.
AB  - Here we report a new role for the small GTPase RhoC in the control of limb
      chondrogenesis. Expression of rhoC is a precocious marker of the zeugopodial and
      digit blastemas and is induced by treatments with TGFbetas preceding the
      formation of ectopic digits. As development progresses, expression of rhoC
      outlines the growing distal tip of the digits, and marks the regions of
      interphalangeal joint formation. Functional experiments show that RhoC is a
      negative regulator of chondrogenesis, which controls digit outgrowth and joint
      segmentation. These functions appear to be mediated by reorganization of the
      actin cytoskeleton and modification of the adhesive properties of the mesenchymal
      cells.

PMID- 17208218
TI  - Runx1 selectively regulates cell fate specification and axonal projections of
      dorsal root ganglion neurons.
AB  - Runx1-deficient mice die around embryonic day 11.5 due to impaired hematopoiesis.
      This early death prevents the analysis of the role of Runx1 in the development of
      sensory ganglia. To overcome the early embryonic lethality, we adopted a new
      approach to utilize transgenic Runx1-deficient mice in which hematopoietic cells
      are selectively rescued by Runx1 expression under the control of GATA-1 promoter.
      In Runx1-deficient mice, the total number of dorsal root ganglion (DRG) neurons
      was increased, probably because of an increased proliferative activity of DRG
      progenitor cells and decreased apoptosis. In the mutant DRG, TrkA-positive
      neurons and peptidergic neurons were increased, while c-ret-positive neurons were
      decreased. Axonal projections were also altered, in that both central and
      peripheral projections of CGRP-positive axons were increased. In the dorsal horn
      of the spinal cord, projections of CGRP-positive axons expanded to the deeper
      layer, IIi, from the normal terminal area, I/IIo. Our results suggest that Runx1
      is involved in the cell fate specification of cutaneous neurons, as well as their
      projections to central and peripheral targets.

PMID- 17208219
TI  - Forced expression of Phox2 homeodomain transcription factors induces a branchio
      visceromotor axonal phenotype.
AB  - What causes motor neurons to project into the periphery is not well understood.
      We here show that forced expression of the homeodomain protein Phox2b, shown
      previously to be necessary and sufficient for branchio-visceromotor neuron
      development, and of its paralogue Phox2a imposes a branchiomotor-like axonal
      phenotype in the spinal cord. Many Phox2-transfected neurons, whose axons would
      normally stay within the confines of the neural tube, now project into the
      periphery. Once outside the neural tube, a fraction of the ectopic axons join the
      spinal accessory nerve, a branchiomotor nerve which, as shown here, does not
      develop in the absence of Phox2b. Explant studies show that the axons of Phox2
      transfected neurons need attractive cues to leave the neural tube and that their
      outgrowth is promoted by tissues, to which branchio-visceromotor fibers normally
      grow. Hence, Phox2 expression is a key step in determining the peripheral axonal
      phenotype and thus the decision to stay within the neural tube or to project out
      of it.

PMID- 17208220
TI  - Nicotine potentiates the nitrergic relaxation responses of rabbit corpus
      cavernosum tissue via nicotinic acetylcholine receptors.
AB  - The presence of neuronal nicotinic acetylcholine receptors in rabbit corpus
      cavernosum tissue and possible mechanisms underlying the potentiation of
      electrical field stimulation induced relaxation by nicotine were analyzed. In
      corpus cavernosum tissue strips nicotine (3 x 10(-5) M) and acetylcholine (10(-3)
      M) produced potentiation on electrical field stimulation (amplitude 50 V;
      frequency 4 Hz; width 0.8 ms) induced relaxation responses. This nicotine-induced
      potentiation was not altered by atropine (10(-6) M), guanethidine (5 x 10(-6) M)
      and indomethacin (10(-5) M), but abolished by hexamethonium chloride (10(-5) M)
      and L-nitro arginine methyl ester (10(-5) M). Nicotine did not cause any
      alteration on a single dose of carbachol (3 x 10(-5) M) and sodium nitroprusside
      (10(-5) M) induced relaxation responses. The results suggest that, nicotine
      induced potentiation is NO and nicotinic acetylcholine receptor dependent but
      independent from prostaglandin synthesis, activation of muscarinic receptors and
      does not require intact adrenergic neurons. Nicotine did not affect smooth muscle
      and endothelium directly. In conclusion, in this study we showed for the first
      time that, nicotine acts on the nicotinic acetylcholine receptors located on the
      nitrergic nerves, thereby evoking the release of NO from these nerve terminals
      inducing relaxation response in rabbit corpus cavernosum tissue.

PMID- 17208221
TI  - CCK2 receptors mediate inhibitory effects of cholecystokinin on the motor
      activity of guinea-pig distal colon.
AB  - Cholecystokinin and related peptides are involved in the control of intestinal
      motility and cholecystokinin receptor ligands might represent new pharmacological
      tools for the treatment of symptoms associated with functional bowel disorders.
      However, the respective roles played by cholecystokinin receptor subtypes and the
      mechanisms underlying these regulatory actions remain undetermined. This study
      was designed to examine the influence of cholecystokinin receptor subtypes on the
      motor activity of guinea-pig distal colon. The effects of drugs acting on CCK1
      and CCK2 receptors were assessed in vitro on the contractile activity of
      longitudinal smooth muscle, both under basal conditions and in the presence of
      transmural electrical stimulation or KCl-induced contractions. The application of
      cholecystokinin octapeptide sulphate (cholecystokinin-8S) to colonic preparations
      induced concentration-dependent contractions which were prevented by devazepide
      (CCK1 receptor antagonist), enhanced by GV150013 (CCK2 receptor antagonist) or
      N(omega)-nitro-L-arginine methylester (L-NAME, nitric oxide synthase inhibitor),
      and unaffected by tetrodotoxin. The application of gastrin-17 to colonic
      preparations resulted in relaxant responses which were insensitive to devazepide,
      and prevented by GV150013, L-NAME or tetrodotoxin. L-NAME, N(omega)-propyl-L
      arginine (NPA, neuronal nitric oxide synthase inhibitor) or GV150013 enhanced
      electrically evoked contractile responses, whereas devazepide did not. When
      tested in the presence of L-NAME or NPA the enhancing effect of GV150013 on
      electrically induced contractions no longer occurred. In the presence of KCl
      induced pre-contractions, cholecystokinin-8S or gastrin-17 evoked concentration
      dependent relaxations, which were unaffected by devazepide and were counteracted
      by GV150013, L-NAME, NPA or tetrodotoxin. In conclusion, the present results
      indicate that, at level of distal colon, CCK1 receptors mediate direct
      contractile effects on smooth muscle, whereas CCK2 receptors on enteric neurons
      mediate relaxant responses via nitric oxide release.

PMID- 17208222
TI  - Thalidomide destabilizes cyclooxygenase-2 mRNA by inhibiting p38 mitogen
      activated protein kinase and cytoplasmic shuttling of HuR.
AB  - We investigated the effect of thalidomide on transcriptional and post
      transcriptional cyclooxygenase-2 (COX-2) expression, including a pathway leading
      to COX-2 mRNA destabilization. We found that thalidomide inhibited the
      interleukin-1beta (IL-1beta)-mediated induction of COX-2 protein and mRNA in Caco
      2 cells. Transient transfection with a COX-2 promoter construct demonstrated that
      thalidomide did not affect IL-1beta-induced transcriptional activation of COX-2,
      although it did decrease the stability of COX-2 mRNA and suppress IL-1beta
      induced cytoplasmic shuttling of an mRNA stabilizing protein, HuR. Thalidomide
      also suppressed IL-1beta-induced p38 mitogen-activated protein kinase (MAPK)
      activation, while a p38 MAPK inhibitor destabilized COX-2 mRNA and the
      cytoplasmic shuttling of HuR induced by IL-1beta. These data suggest that one of
      the molecular mechanisms of thalidomide may be destabilization of COX-2 mRNA
      through inhibition of cytoplasmic shuttling of HuR and p38 MAPK.

PMID- 17208223
TI  - Histone acetyltransferase p300 modulates gene expression in an epigenetic manner
      at high blood alcohol levels.
AB  - When rats are fed ethanol intragastrically at a constant rate for 1 month, the
      urinary alcohol level (UAL) cycles over 7-9 day intervals. At the peak UAL, the
      liver is hypoxic shifting the redox state to a reduced rate. Microarray analysis
      done on livers at the UAL peaks shows changes in approximately 1300 gene
      expression compared to the pair-fed controls. To determine the mechanism of the
      gene expression changes, histone acetylation regulation was investigated in liver
      nuclear extracts at the peaks and troughs of the UAL and their pair-fed controls.
      No change occurred in SirT-1. P300, a histone acetyltransferase (HAT), which
      acetylates histone H3 on lysine 9, was increased at the peaks. Histone 3
      acetylated at lysine 9 was also increased at the peaks. This indicates that the
      up regulated genes at the UAL peaks resulted from an increase in p300
      transcription regulation, epigenetically. P300 activates transcription of
      numerous genes in response to signal transcription factors such as H1F 1alpha,
      increased in the nucleus at UAL peaks. Signal transduction pathways, such as
      NFkappaB, AP-1, ERK, JNK, and p38 were not increased at the peaks. beta-Catenin
      was increased in the nuclear extract at the UAL troughs, where increased gene
      expression was absent. The increase in gene expression at the peaks was due, in
      part, to increased acetylation of histone 3 at lysine 9.

PMID- 17208224
TI  - Increased expression of inhibitor of apoptosis proteins in atherosclerotic
      plaques of symptomatic patients with carotid stenosis.
AB  - Vascular remodeling and atheromatous lesion formation are determined in part by
      the balance between apoptosis and survival of vascular smooth muscle cells
      (VSMCs). In the chronic stages, apoptosis of VSMCs in the atherosclerotic plaques
      contributes to the weakening and potential rupture of the plaque causing
      pathologies such as acute coronary syndrome. The higher incidence of apoptosis in
      the plaques of symptomatic than in asymptomatic patients has been demonstrated,
      but the expression of survival proteins, including the inhibitor of apoptosis
      proteins (IAPs), has not been thoroughly examined. The aim of this study was to
      investigate the immunohistochemical expression of cellular inhibitor of apoptosis
      protein-2 (cIAP2), x-linked inhibitor of apoptosis protein (XIAP), and survivin
      in normal carotid arteries, and carotid endarterectomy specimens of symptomatic
      and asymptomatic patients with carotid stenosis. The results demonstrated
      stronger immunopositivity to smooth muscle myosin heavy chain antigen (SM-MHC)
      (sm2), proliferating cell nuclear antigen (PCNA), and p50 subunit of NF-kappabeta
      in the asymptomatic plaques than in symptomatic plaques. Furthermore, there was
      higher expression of cIAP2, XIAP, and survivin in the symptomatic than in the
      asymptomatic plaques and this paralleled caspase-3 expression. The increased
      expression of IAPs in symptomatic plaques could be due to endogenous defense
      mechanism to protect against the pro-apoptotic effect of the inflammatory stimuli
      that are released in the plaques. This could be involved in the stabilization of
      symptomatic atheromatous plaques and may prove a potential therapeutic target.

PMID- 17208225
TI  - Neutrophil activation and arteritis induced by C. albicans water-soluble
      mannoprotein-beta-glucan complex (CAWS).
AB  - We have established a mouse model which shows the symptoms of coronary arteritis
      after consecutive injections of CAWS, which is released from Candida albicans. In
      this study, we examined neutrophil activation in the initial period after CAWS
      injection intraperitoneally. During 10 min to 16 h after the injection, blood
      profiles and neutrophil functions were determined. At the same time, levels of
      inflammatory cytokines and chemokines in plasma were measured. Furthermore, level
      of ICAM-1 as a marker of lesion in arterial endothelial cells was measured.
      Counts of the peripheral leukocytes increased immediately after CAWS injection,
      especially involving neutrophil. In vitro sensitivity of neutrophils to stimuli
      was enhanced. Moreover, proinflammatory cytokines (IL-1beta, IL-12 and IL-6)
      increased in plasma initially followed by an increase in IL-10, G-CSF, MIP-2 and
      soluble ICAM-1. Locally, ICAM-1 message in arterial walls was significantly
      increased 16 h after CAWS injection. A decrease in C3 levels was observed in
      plasma, suggesting complement activation and consumption. In summary, neutrophil
      activation occurred after CAWS injection, followed by complement activation, and
      production of proinflammatory cytokines chemokines and G-CSF which may be
      involved in development of coronary arteritis.

PMID- 17208227
TI  - New quantitative analysis, using high-resolution images, of oxygen-induced
      retinal neovascularization in mice.
AB  - Oxygen-induced retinopathy (OIR) has been widely studied as an animal model of
      retinal neovascularization diseases. Evaluation using this model is mainly
      performed by counting cell nuclei above the internal limiting membrane in serial
      cross-sections or by scoring in flat-mounted retinas. Quantitative evaluation is
      important for accurate elucidation of pathological conditions and the drug
      evaluations. We therefore attempted quantification using new imaging software and
      high-resolution images taken with a high-resolution CCD camera. Neonatal mice
      were exposed to 75% oxygen from postnatal day 7 (P7) to P12, then returned to
      room air until P17. At each evaluation time, mice were perfused with fluorescein
      dextran, and flat-mounted retinas were prepared. Total images of the retinal
      vasculature were collected and analyzed using the imaging software. P17 normal
      retinas showed increases in computerized total tube area, total tube length,
      number of segments, and number of branch points (versus P7 normal retinas). These
      increases coincided with the development of the retinal vasculature between P7
      and P17. P17 OIR retinas similarly showed increases in those parameters, and the
      number of nodes (thick regions exceeding the maximum width of the vessel) and the
      node area (abnormality induced by OIR) were markedly increased (versus P17 normal
      retinas). Accordingly, this approach is considered most suitable for evaluating
      the number of nodes and node area in this model. Quantification using the present
      imaging software should be useful for evaluating physiological and pathological
      neovascularizations in this OIR model.

PMID- 17208226
TI  - Single-cell-derived mesenchymal stem cells overexpressing Csx/Nkx2.5 and GATA4
      undergo the stochastic cardiomyogenic fate and behave like transient amplifying
      cells.
AB  - Bone marrow-derived stromal cells can give rise to cardiomyocytes as well as
      adipocytes, osteocytes, and chondrocytes in vitro. The existence of mesenchymal
      stem cells has been proposed, but it remains unclear if a single-cell-derived
      stem cell stochastically commits toward a cardiac lineage. By single-cell
      marking, we performed a follow-up study of individual cells during the
      differentiation of 9-15c mesenchymal stromal cells derived from bone marrow
      cells. Three types of cells, i.e., cardiac myoblasts, cardiac progenitors and
      multipotent stem cells were differentiated from a single cell, implying that
      cardiomyocytes are generated stochastically from a single-cell-derived stem cell.
      We also demonstrated that overexpression of Csx/Nkx2.5 and GATA4, precardiac
      mesodermal transcription factors, enhanced cardiomyogenic differentiation of 9
      15c cells, and the frequency of cardiomyogenic differentiation was increased by
      co-culturing with fetal cardiomyocytes. Single-cell-derived mesenchymal stem
      cells overexpressing Csx/Nkx2.5 and GATA4 behaved like cardiac transient
      amplifying cells, and still retained their plasticity in vivo.

PMID- 17208228
TI  - Lymphocytic infiltration and goblet cell marker alteration in the conjunctiva of
      the MRL/MpJ-Fas(lpr) mouse model of Sjogren's syndrome.
AB  - Sjogren's syndrome is an autoimmune disorder characterized by a progressive,
      immune-mediated destruction of mucosal tissues such as the lacrimal and salivary
      glands, leading to ocular and oral dryness. The MRL/MpJ-Fas(lpr) mouse is one of
      the animal models used to study this disease. However, little is known about the
      potential alterations in the conjunctiva in this murine model. The purpose of
      this study was to determine: (1) whether the conjunctiva is infiltrated by T
      lymphocytes, (2) characterize the type, amount and temporal sequence of the
      inflammatory infiltrates, and (3) investigate whether the amount of conjunctival
      goblet cells is altered in this murine model of Sjogren's syndrome. Female 4-, 9
      , 13-, 16-, and 18-/20-wk-old MRL/MpJ-Fas(lpr) (lpr, diseased) and congenic
      MRL/MpJ (+/+, control) mice were used. Right eyes were either fixed, frozen,
      cryosectioned, and studied by immunofluorescence microscopy or the conjunctiva
      was removed, homogenized and analyzed by electrophoresis and Western blot
      analysis. The following antibodies were used: anti-CD3 (specific T lymphocyte
      marker), anti-cytokeratin 7 (CK-7), anti-PKD (formerly known as PKCmu, both
      markers of goblet cell bodies), anti-PGP 9.5 (pan-neuronal marker), anti-VIP and
      TH (markers for parasympathetic and sympathetic nerves, respectively), anti
      adrenergic (alpha(1) and beta(1-3)) and muscarinic (M(1)-M(3)) receptor subtypes
      (markers for neurotransmitter receptors of the sympathetic and parasympathetic
      pathways, respectively). Left eyes were fixed, embedded, sectioned, and stained.
      Hematoxylin/eosin, Giemsa, or alcian blue/periodic acid Schiff's reagent were
      used to study lymphocyte infiltration; to determine the presence of eosinophils,
      neutrophils, and mast cells; and to count the number of goblet cells,
      respectively. By immunofluorescence microscopy, lymphocytes were detected in the
      conjunctiva of 9-wk-old lpr, but not +/+, mice. The lymphocytic infiltration
      became more extensive as the animals aged, with 16- and 18-/20-wk lpr mice
      appearing to have a greater lymphocytic infiltration than +/+ mice at the same
      age. By Western blot analysis, the amount of CD3 was enhanced in lpr compared to
      +/+ mice by the 16th wk, but not by the 9th wk. No major differences in the
      presence of eosinophils, neutrophils and degranulated mast cells between lpr and
      +/+ mice were observed. By light microscopy, a significant increase in goblet
      cell number was found in lpr mice compared to +/+ mice at 16 wks on. By Western
      blotting, the amount of CK-7 was significantly increased at 9 wks on and the
      amount of PKD was significantly increased at 16 wks. By immunofluorescence
      microscopy, there were no major differences in distribution of sympathetic and
      parasympathetic nerves present in the lpr conjunctiva compared to that of +/+
      mice at any ages, although slight differences were observed with increased age.
      Muscarinic receptor expression was decreased, as less M(3) receptor subtype
      associated immunofluorescence was detected in older lpr mice compared to +/+ mice
      and confirmed by Western blot analysis. No differences in the localization or the
      amount of alpha(1)- or beta(1-3)-adrenergic receptor immunodetection were
      observed between lpr and +/+ mice. We conclude that the conjunctiva is a target
      tissue in Sjogren's syndrome-related inflammation in this murine model.

PMID- 17208230
TI  - Stem cell transplantation for Huntington's disease.
AB  - By way of commentary on a recent report that transplanted adult neural progenitor
      cells can alleviate functional deficits in a rat lesion model of Huntington's
      disease [Vazey, E.M., Chen, K., Hughes, S.M., Connor, B., 2006. Transplanted
      adult neural progenitor cells survive, differentiate and reduce motor function
      impairment in a rodent model of Huntington's disease. Exp. Neurol. 199, 384-396],
      we review the current status of the field exploring the use of stem cells,
      progenitor cells and immortalised cell lines to repair the lesioned striatum in
      animal models of the human disease. A remarkably rich range of alternative cell
      types have been used in various animal models, several of which exhibit cell
      survival and incorporation in the host brain, leading to subsequent functional
      recovery. In comparing the alternatives with the 'gold standard' currently
      offered by primary tissue grafts, key issues turn out to be: cell survival,
      differentiation prior to and following implantation into striatal-like
      phenotypes, integration and connectivity with the host brain, the nature of the
      electrophysiological, motor and cognitive tests used to assess functional repair,
      and the mechanisms by which the grafts exert their function. Although none of the
      alternatives yet has the capacity to match primary fetal tissues for functional
      repair, that standard is itself limited, and the long term goal must be not just
      to match but to surpass present capabilities in order to achieve fully functional
      reconstruction reliably, flexibly, and on demand.

PMID- 17208229
TI  - Treatment of experimental autoimmune uveoretinitis with atorvastatin and
      lovastatin.
AB  - Statins, which are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitors, are approved for cholesterol reduction and are commonly used to treat
      atherosclerosis and coronary artery disease. Statins may also be potent
      immunomodulatory agents and may be beneficial in the treatment of autoimmune
      diseases. In this study, we investigated therapeutic effects of atorvastatin and
      lovastatin on experimental autoimmune uveoretinitis (EAU). EAU was induced in
      Lewis rats using bovine S-antigen (S-Ag) peptide. Atorvastatin was suspended in
      0.5% aqueous methylcellulose and was administered orally at a dose of 10 mg/kg
      and at a low-dose of 1 mg/kg. Lovastatin was dissolved in DMSO:PBS (1:1) and was
      administered by intraperitoneal (i.p.) injection at a dose of 2 mg/kg. Both
      statin treatments were initiated after the clinical onset once daily for 14 days.
      The rats were examined every other day for clinical signs of EAU. The
      histological scores and delayed-type hypersensitivity (DTH) were evaluated on day
      28 post-immunization. Morphologic and immunohistochemical examinations were
      performed with light and confocal microscopy, respectively. Lymphocyte
      proliferation was measured by [(3)H]thymidine incorporation into antigen
      stimulated T cells from inguinal lymph nodes. After 72 h, supernatants were
      collected and assayed for IFN-gamma by ELISA. Clinical and histological scores of
      EAU were decreased in both the atorvastatin (10 mg/kg)- and lovastatin (2 mg/kg)
      treated groups. The invasion of T cells and macrophages, and Muller cell
      proliferation, were inhibited in both atorvastatin- and lovastatin-treated
      groups. DTH was significantly inhibited in both groups, compared with vehicle
      treated groups (controls). Lymphocyte proliferation assay demonstrated decreased
      proliferation in the presence of 25 microg/ml S-Ag peptide in both groups,
      compared with controls. In the supernatants of lymph node cells stimulated with S
      Ag peptide (5 microg/ml), 77 or 87% inhibition of IFN-gamma production was
      observed in rats treated with atorvastatin or lovastatin, respectively, compared
      with controls. The current results indicate that atorvastatin administrated
      orally following the clinical onset has therapeutic effect in EAU as well as
      lovastatin administrated intraperitoneally. Statins may be useful for treating
      intraocular inflammation.

PMID- 17208231
TI  - Differential regulation of neurotrophins and serotonergic function in mice with
      genetically reduced glucocorticoid receptor expression.
AB  - The neurotrophin and serotonin (5-HT) hypotheses of depression were studied in a
      mouse model of reduced glucocorticoid receptor (GR) function (GR(+/-) mice),
      which recently has been proven as a murine model of predisposition for depressive
      behaviour under stressful conditions. In this model we studied diurnal changes in
      neurotrophins and serotonergic function in candidate brain regions mediating
      depressive behaviour. Morning and evening levels of brain-derived neurotrophic
      factor (BDNF), nerve growth factor (NGF), 5-HT and its metabolite 5
      hydroxyindoleacetic acid (5-HIAA) were analyzed in representative brain regions
      of GR(+/-) and wildtype mice. The diurnal variation of hippocampal BDNF in
      wildtypes with higher levels in the morning was absent in GR(+/-) mice.
      Hypothalamus and parietal cortex displayed enhanced BDNF levels in GR(+/-) mice.
      In the frontal cortex, striatum and hypothalamus NGF increased from morning to
      evening in both genotypes, with an exaggeration in GR(+/-) mice. The diurnal
      variation of 5-HT levels and turnover did not differ significantly between
      genotypes. It was only in the hypothalamus that the evening level of 5-HIAA was
      lower in GR(+/-) mice than in wildtype mice. In conclusion, the present data
      indicate a contribution of altered BDNF and NGF protein levels to the
      predisposition for depressive behaviour in the GR(+/-) mouse model of depression,
      but argue against an eminent role of the serotonergic system.

PMID- 17208232
TI  - p53 regulates ERK activation in carboplatin induced apoptosis in cervical
      carcinoma: a novel target of p53 in apoptosis.
AB  - In general, the activation of extracellular recognition kinase (ERK) cascade is
      implicated in exerting tumorigenic effects. Conversely, recent studies suggest
      that ERK activation may also have role in DNA-damage induced apoptosis [Wang, X.,
      Martindale, J.L. and Holbrook, N.J. (2000) Requirement for ERK activation in
      cisplatin-induced apoptosis. J. Biol. Chem. 275, 39435-39443; Schweyer S., Soruri
      A., Meschter O., Heintze A., Zschunke F., Miosge N., Thelen P., Schlott T.,
      Radzun H.J. and Fayyazi, A. (2004) Cisplatin-induced apoptosis in human malignant
      testicular germ cell lines depends on MEK/ERK activation. Br. J. Cancer 91, 589
      598]. Here we observed an essential requirement of ERK activation in carboplatin
      (Carb) induced apoptosis in SiHa and CaSki cells. Under similar treatment
      conditions p53 was also involved in Carb induced apoptosis in these cells.
      Therefore, we investigated the relation between p53 and ERK in Carb induced
      apoptosis in these cells. Abrogation of p53 transactivation activity by pifithrin
      alpha or dominant-negative mutant of p53 resulted in decrease in activation of
      ERK in Carb treated cells. The present study for the first time proposes that p53
      may act as one of the upstream regulators of ERK activation for the induction of
      apoptosis in Carb treated cervical cancer cells.

PMID- 17208233
TI  - Intracellular route and mechanism of action of ERB-hRNase, a human anti-ErbB2
      anticancer immunoagent.
AB  - Human anti-ErbB2 immunoRNase with Erbicin fused to HP-RNase (ERB-hRNase) is a
      fully human immunoRNase made up of human pancreatic RNase fused to a human anti
      ErbB2 scFv. It binds selectively with high affinity to ErbB2-positive cells, and
      specifically inhibits their proliferation, in vitro and in vivo. An investigation
      of its mechanism of action and its intracellular destination has revealed that
      ERB-hRNase depends on its RNase activity for cytotoxic action; it reaches the
      cytosol directly from the endosomal compartment; it is inhibited by the cytosolic
      RNase inhibitor (cRI), but the levels that ERB-hRNase reaches in the cytosol
      neutralize cRI, thus inducing cell death by apoptosis.

PMID- 17208234
TI  - Identification of a novel bifunctional delta12/delta15 fatty acid desaturase from
      a basidiomycete, Coprinus cinereus TD#822-2.
AB  - A new gene encoding a delta12 fatty acid desaturase-related protein was cloned
      from a multicellular basidiomycete Coprinus cinereus TD#822-2. The 1326 bp full
      length gene, designated as Cop-odeA, codes for a putative protein of 442 amino
      acids with a MW of 49224. The Cop-odeA yeast transformant accumulated four new
      fatty acids identified as 9,12-hexadecadienoic acid, 9,12,15-hexadecatrienoic
      acid, linoleic acid, and alpha-linolenic acid, which comprised 8.8%, 1.0%, 29.0%,
      and 0.6% of the total fatty acids, respectively. The Cop-odeA protein was
      confirmed to be a novel bifunctional fatty acid desaturase with both high delta12
      desaturase activity and unusual delta15 desaturase activity.

PMID- 17208235
TI  - Supernumerary minute ring chromosome 14 in a man with primary infertility and
      left varicocele.
AB  - OBJECTIVE: To describe a case of supernumerary minute ring chromosome (SMRC) in
      an infertile man, with the concurrent finding of a left varicocele. DESIGN: Case
      report. SETTING: Urologic infertility clinic in a university hospital.
      PATIENT(S): Male patient presenting with primary infertility. INTERVENTION(S):
      Karyotyping, genetic counseling, and microsurgical left varicocelectomy. MAIN
      OUTCOME MEASURE(S): Sperm concentration and motility, chromosomal number and
      structure. RESULT(S): Fluorescence in situ hybridization revealing SMRC 14. Sperm
      concentration and motility improved after left varicocele repair. CONCLUSION(S):
      A karyotype should be included in the evaluation of severe oligospermia. Although
      SMRC 14 may be associated with fertility problems, repair of a coexisting
      varicocele should be considered in these patients.

PMID- 17208236
TI  - Protein-losing enteropathy from eosinophilic enteritis diagnosed by wireless
      capsule endoscopy and double-balloon enteroscopy.

PMID- 17208237
TI  - PEG-tube placement in a patient with extreme obesity: overcoming the technical
      challenges.

PMID- 17208238
TI  - Chronic lymphocytic leukemia manifesting as ischemic colitis.

PMID- 17208239
TI  - Small-bowel adenocarcinoma diagnosed via capsule endoscopy in a patient found to
      have hereditary nonpolyposis colorectal cancer.

PMID- 17208241
TI  - Treatment of tracheoesophageal fistula in a child by using an endoscopic suturing
      device.

PMID- 17208240
TI  - Colonic cryptococcus infection.

PMID- 17208242
TI  - Hepatitis C virus cross-infection during endoscopy: is it the "tip of the
      iceberg" or the absence of ice?

PMID- 17208243
TI  - Ion-trap tandem mass spectrometry-based analytical methodology for the
      determination of polychlorinated biphenyls in fish and shellfish. Performance
      comparison against electron-capture detection and high-resolution mass
      spectrometry detection.
AB  - Optimization of the Varian Saturn 2200 ion-trap tandem mass spectrometry (IT
      MS/MS) system and comparison of its data quality with two other detection methods
      [electron-capture detection (ECD) and high-resolution mass spectrometry (HRMS)]
      was pursued by measuring polychlorinated biphenyls (PCBs) levels in fish and
      shellfish samples. IT-MS/MS methodology provided limits of detection (LOD)
      comparable to those obtained by ECD but superior specificity for the detection of
      a selected number of 39 PCB native congeners and 9 (13)C-labelled PCB standards.
      The method detection limits (MDLs) established for IT-MS/MS ranged between 1.0
      and 5.0 pg/g on a wet weight basis while those obtained by ECD and HRMS were 1.0
      4.0 pg/g and 0.1-2.0 pg/g, respectively. Overall, the results obtained in the
      study demonstrate that gas chromatography (GC) combined with IT-MS/MS provide
      higher data quality than those achievable by GC-ECD. For this particular set of
      target analytes the specificity achievable with IT-MS/MS was comparable to that
      obtained by HRMS and both techniques provided comparable data in terms of
      accuracy and precision.

PMID- 17208244
TI  - Simultaneous and trace determination of reduced and oxidized glutathione in
      minute plasma samples using dual mode fluorescence detection and column switching
      high performance liquid chromatography.
AB  - A robust method for the simultaneous quantification of endogenous reduced
      glutathione (GSH) and oxidized glutathione (GSSG) in as little as 5 microl human
      plasma employing two-dimensional chromatographic system with parallel Hypercarb
      columns coupled with dual fluorescence detectors (FLD) has been developed. After
      sample preparation, 10 microl of supernatant was injected into the
      chromatographic system. The limits of detection (LOD) of GSH and GSSG were 0.5
      and 0.040 pmol on column, respectively. Derivatization of GSH and GSSG with
      monobromobimane (MBB) and ortho-phthalaldehyde (OPA) provides a sensitivity and
      specificity that allows analysis after fingertip sampling, blood sampling from
      infants or multiple blood sampling from mice or other small experimental animals
      without sacrificing the animal.

PMID- 17208246
TI  - Immunoassay by capillary electrophoresis with quantum dots.
AB  - The application of quantum dots in capillary electrophoresis immunoassay was
      studied for the first time. Quantum dots were conjugated with antibody and
      subsequently tested by electrophoretic separation of free antibody and antibody
      antigen complex. Antibody was fluorescently labeled by quantum dots via
      conjugation procedures and its electrophoretic characteristics were effectively
      modified due to the attachment of quantum dots. The determination of human IgM by
      direct CE based immunoassay could be easily achieved by simply changing the pH
      value of separation buffer. Polymer additive influenced the separation too but
      the effect was not as significant as buffer pH adjustment. Satisfactory
      separation of complex from free antibody could be achieved with 20mM sodium
      tetraborate as separation buffer, at pH 9.8. The immunoassay application of
      quantum dots in CE offers considerable advantages and can be readily applied to
      other large bio-molecules.

PMID- 17208247
TI  - On-line size exclusion chromatography-pyrolysis-gas chromatography-mass
      spectrometry for copolymer characterization and additive analysis.
AB  - On-line coupled size exclusion chromatography-pyrolysis gas chromatography mass
      spectrometry (SEC-Py-GC-MS) is studied as a novel tool for the characterization
      of complex polymer samples. An automated system for on-line SEC-Py-GC-MS allowing
      transfer of multiple fractions was developed based on stop-flow operation of the
      SEC dimension, syringe-based transfer of the SEC fraction to the GC instrument
      and solvent elimination with subsequent pyrolysis in a programmed temperature
      vaporization (PTV) injector. After optimization the system was applied to the
      characterization of a complex terpolymer composed of very similar monomers. The
      use of the system for combined pyrolysis and additive analyses in polycarbonate
      was also demonstrated. Results obtained with the new method indicate the
      interesting potentials of the method for detailed characterization of polymeric
      materials.

PMID- 17208248
TI  - Nonlinear friction characteristics between silica surfaces in high pH solution.
AB  - Molecular-scale characteristics of friction forces between silica particles and
      silica wafers in aqueous solutions of the normal (pH 5.6) and high pH (pH 10.6)
      are investigated, using the lateral force measuring procedure of the atomic force
      microscope (AFM). Various significant differences of friction characteristics
      between solutions of normal and high pH's are found. In the case of solutions of
      normal pH, the friction force increases linearly with increasing loading force,
      as the Amonton's law for solid bodies indicates. However, in the case of high pH
      solutions, the increasing rate with the loading force is considerably reduced in
      the low loading region, but the value increases abruptly above a critical loading
      force to overcome the magnitude of friction force of normal pH above the region
      of very high loading. It is very interesting to know that this nonlinear force
      curve at high pH is independent of the atomic-scale roughness of surfaces,
      although the magnitude of friction is greatly influenced by the roughness in the
      case of normal pH. The reason why the friction at high pH is independent of the
      surface roughness is postulated to be due to the hairy-like layer formed on the
      silica surface. The existence of hairy-like layers at high pH is proven directly
      by the dynamic method of normal force measurements with AFM and the thickness is
      estimated to be at least ca. 1.3 nm.

PMID- 17208249
TI  - Turbidimetric study of fluorite nucleation in solution.
AB  - Precipitation of fluorite (calcium fluoride) from solution at 30 and 37 degrees C
      has been studied by measurement of turbidity at different wavelengths, analyzing
      the data with the aid of the Mie theory of light scattering from small particles.
      In this way both number density and average particle size were obtained as
      functions of time. The values were confirmed by sedimentation analysis. In the
      later part of the process the results were strongly influenced by agglomeration
      and sedimentation, but the initial part of the curve of number density vs time
      was useful in determination of nucleation kinetics. The trend of nucleation
      frequency vs supersaturation agreed well with the classical theory of Becker,
      Doring, Volmer, Zel'dovich, and Frenkel, and surface energies equal to 102
      mJ/m(2) at 30 degrees C and 89 mJ/m(2) at 37 degrees C were found. On the other
      hand, the absolute rate of nucleation was many orders of magnitude lower than
      that predicted by the theory, which is ascribed to an overestimate of the rate of
      growth of postcritical nuclei.

PMID- 17208250
TI  - Thermodynamic analysis of the immersion of a smectite substituted with Na or Ca:
      heat effect due to the cation.
AB  - The enthalpy produced during immersion in water of a smectite, identified as a
      montmorillonite, substituted by Ca or Na is analyzed using three different
      approaches. The heat of immersion is measured using the classical calorimetric
      method. It is compared to an estimate using adsorption techniques. And it is
      calculated from a theoretical estimate of the surface energy of a crystal model
      of montmorillonite. The comparison of the different values allows the enthalpy
      linked to the swelling phenomenon to be estimated. The Ca form appears in every
      case to interact more strongly with water molecules than the Na form.

PMID- 17208251
TI  - Page charges and unfunded investigators.

PMID- 17208252
TI  - Zebrafish (Danio rerio) whole kidney assays to measure neutrophil extracellular
      trap release and degranulation of primary granules.
AB  - The zebrafish (Danio rerio) is an excellent model system for studies in
      developmental biology, genetics, and toxicology, and is increasingly gaining
      importance in the field of immunology. The use of whole zebrafish kidneys as
      source of neutrophils for degranulation assays and detection of neutrophil
      extracellular traps is described for the first time. Neutrophils from zebrafish
      kidneys released neutrophil extracellular traps (NETs) and myeloperoxidase (MPO)
      upon stimulation with calcium ionophore, phorbol myristate acetate, and beta
      glucan. Immunocytochemical study of zebrafish kidney cells revealed that NETs are
      made of DNA fibers associated with neutrophil granular proteins, but not with
      cytoskeleton. Rapid, direct MPO and extracellular DNA detection assays were
      developed to quantify NET release and degranulation of neutrophil primary
      granules from whole zebrafish kidneys. The assays were used to measure the
      effects of acute crowding and handling stress on neutrophils, and to examine the
      potential for use of zebrafish whole kidney assays in evaluation of neutrophil
      function under different conditions in vivo. The whole kidney NET release and
      degranulation assays are quantitative, can rapidly measure a large number of
      samples, and are capable of detecting inhibition of neutrophil activity in
      stressed fish, overcoming the limitations that prevented use of zebrafish in the
      investigations of cellular innate immune function. The assays can be used as a
      new research model to study effects of stress, immunomodulators, toxicants, and
      diseases on fish neutrophil biology.

PMID- 17208253
TI  - Thermostability/infectivity defect caused by deletion of the core protein V gene
      in human adenovirus type 5 is rescued by thermo-selectable mutations in the core
      protein X precursor.
AB  - Mastadenoviruses represent one of the four major genera of the Adenoviridae
      family comprising a variety of mammalian pathogens including human adenovirus
      (Ad), whose genomes encode a gene for minor core protein V (pV), not found in
      other genera of Adenoviridae. Deletion of other genus-specific genes (gene IX and
      E3 genes) from the Ad type 5 (Ad5) genome has been studied experimentally in
      vitro and the results on biological characterization of the mutants support the
      phylogenetic evidence of those genes being non-essential for Ad viability. On
      this basis it seemed logical to suggest that a deletion of gene V from the Ad5
      genome could also be tolerated. To test this hypothesis we constructed and
      rescued the first pV-deletion mutant of human Ad5. As compared to Ad5, this
      mutant formed small plaques, had dramatically reduced thermostability and lower
      infectivity. A subsequent thermoselection screen of the pV-deleted Ad5 allowed
      isolation of a suppressor mutant Ad5-dV/TSB with restored biological
      characteristics. Since replication and viral assembly of Ad5-dV/TSB could still
      occur in the absence of pV, we conclude that pV is a non-essential component of
      the virion. The observed rescue of the biological defects appears to be
      associated with a cluster of point mutations in the gene encoding the precursor
      for the other core protein, X/Mu. This finding, thus, suggests possible roles of
      pV and protein X/Mu precursor in viral assembly. It also provides an interesting
      insight into genetic events that mediate molecular adaptation of viruses to
      possible changes in the genetic background in the course of their evolutionary
      divergence. The possible mechanism of the observed genetic suppression is
      discussed.

PMID- 17208255
TI  - In vitro apoptotic activity of 2,2-diphenyl-1,3,2-oxazaborolidin-5-ones in L5178Y
      cells.
AB  - Compounds containing B-N bonds have shown interesting biological activity. One
      class of such molecules is the 2,2-diphenyl-1,3,2-oxazaborolidin-5-ones (3a-j),
      which contain a B-N bond, have an alpha-amino acid moiety in the heterocycle, and
      have an exocyclic moiety related to an amino acid. The purpose of this work was
      to determine the inhibitory effects of 3a-j on the proliferation of murine L5178Y
      lymphoma cells. A new five-membered heterocyclic nucleus with apoptotic activity
      was found. The target products showed potent cytotoxicity in the L5178Y cell
      line. Among them, 3a exhibited the highest antineoplastic activity in L5178Y
      cells with an IC(50) value of 22.5+/-0.2 microM.

PMID- 17208256
TI  - Gamma-decanolactone effect on behavioral and genotoxic parameters.
AB  - Gamma-decanolactone is a monoterpene compound, which is shown to be active in
      some animal models. The psychopharmacological evaluation of this compound in mice
      has revealed that it has a dose-dependent effect on the central nervous system,
      including hypnotic, anticonvulsant and hypothermic activities. The aim of the
      present study was to evaluate the effect of gamma-decanolactone at 0.1 and 0.3
      g/kg on behavior parameters related to plus-maze, open field and forced swim
      tests. In addition, we investigated its genotoxic activity. Gamma-decanolactone
      at the dose of 0.3 g/kg, but not 0.1 g/kg, decreased the number of crossings and
      rearings and there were no significant differences among groups regarding the
      latency to start locomotion in open field. A single i.p. administration of gamma
      decanolactone, at the higher, but not at lower dose used, was able to increase
      the exploratory activity in the test session (24 h after training), as assessed
      by the number of rearings performed in open field, and induced DNA damage on
      brain tissue as measured in comet assay, suggesting an impairment of
      nonassociative, nonaversive learning and a genotoxic effect on CNS. Gamma
      decanolactone did not change the behavior of animals in plus-maze and forced swim
      tests, suggesting this compound shows no anxiolytic or antidepressant activity.

PMID- 17208254
TI  - Decreased protein kinase C (PKC) in platelets of pediatric bipolar patients:
      effect of treatment with mood stabilizing drugs.
AB  - Pediatric bipolar disorder (PBD) is a major public health concern, however, its
      neurobiology is poorly understood. We, therefore, studied the role of protein
      kinase C (PKC) in the pathophysiology of bipolar illness. We determined PKC
      activity and immunolabeling of various PKC isozymes (i.e., PKC alpha, PKC betaI,
      PKC betaII, and PKC delta) in the cytosol and membrane fractions of platelets
      obtained from PBD patients and normal control subjects. PKC activity and PKC
      isozymes were also determined after 8 weeks of pharmacotherapy of PBD patients
      (n=16) with mood stabilizers. PKC activity and the protein expression of PKC
      betaI and betaII, but not PKC alpha or PKC delta, were significantly decreased in
      both membrane as well as cytosol fractions of platelets obtained from medication
      free PBD patients compared with normal control subjects. Eight weeks of
      pharmacotherapy resulted in significantly increased PKC activity but no
      significant changes in any of the PKC isozymes in PBD patients. These results
      indicate that decreases of specific PKC isozymes and decreased PKC activity may
      be associated with the pathophysiology of PBD and that pharmacotherapy with mood
      stabilizing drugs results in an increase and normalization of PKC activity along
      with improvement in clinical symptoms.

PMID- 17208257
TI  - Schizosaccharomyces pombe Rad22A and Rad22B have similar biochemical properties
      and form multimeric structures.
AB  - The Saccharomyces cerevisiae Rad52 protein has a crucial role in the repair of
      DNA double-strand breaks by homologous recombination. In vitro, Rad52 displays
      DNA binding and strand annealing activities and promotes Rad51-mediated strand
      exchange. Schizosaccharomyces pombe has two Rad52 homologues, Rad22A and Rad22B.
      Whereas rad22A deficient strains exhibit severe defects in repair and
      recombination, rad22B mutants have a much less severe phenotype. To better
      understand the role of Rad22A and Rad22B in double-strand break repair, both
      proteins were purified to near homogeneity. Using gel retardation and filter
      binding assays, binding of Rad22A and Rad22B to short single-stranded DNAs was
      demonstrated. Binding of Rad22A to double-stranded oligonucleotides or linearized
      plasmid molecules containing blunt ends or short single-stranded overhangs could
      not be detected. Rad22B also does not bind efficiently to short duplex
      oligonucleotides but binds readily to DNA fragments containing 3'-overhangs.
      Rad22A as well as Rad22B efficiently promote annealing of complementary single
      stranded DNAs. In the presence of Rad22A annealing of complementary DNAs is
      almost 90%. Whereas in reactions containing Rad22B the maximum level of annealing
      is 60%, most likely due to inhibition of the reaction by duplex DNA. Gel
      filtration experiments and electron microscopic analyses indicate self
      association of Rad22A and Rad22B and the formation of multimeric structures as
      has been observed for Rad52 in yeast and man.

PMID- 17208258
TI  - A mild mutator phenotype arises in a mouse model for malignancies associated with
      neurofibromatosis type 1.
AB  - Defects in genes that control DNA repair, proliferation, and apoptosis can
      increase genomic instability, and thus promote malignant progression. Although
      most tumors that arise in humans with neurofibromatosis type 1 (NF1) are benign,
      these individuals are at increased risk for malignant peripheral nerve sheath
      tumors (MPNST). To characterize additional mutations required for the development
      of MPNST from benign plexiform neurofibromas, we generated a mouse model for
      these tumors by combining targeted null mutations in Nf1 and p53, in cis.
      CisNf1+/-; p53+/- mice spontaneously develop PNST, and these tumors exhibit loss
      of-heterozygosity at both the Nf1 and p53 loci. Because p53 has well
      characterized roles in the DNA damage response, DNA repair, and apoptosis, and
      because DNA repair genes have been proposed to act as modifiers in NF1, we used
      the cisNf1+/-; p53+/- mice to determine whether a mutator phenotype arises in NF1
      associated malignancies. To quantitate spontaneous mutant frequencies (MF), we
      crossed the Big Blue mouse, which harbors a lacI transgene, to the cisNf1+/-;
      p53+/- mice, and isolated genomic DNA from both tumor and normal tissues in
      compound heterozygotes and wild-type siblings. Many of the PNST exhibited
      increased mutant frequencies (MF=4.70) when compared to normal peripheral nerve
      and brain (MF=2.09); mutations occurred throughout the entire lacI gene, and
      included base substitutions, insertions, and deletions. Moreover, the brains,
      spleens, and livers of these cisNf1+/-; p53+/- animals exhibited increased mutant
      frequencies when compared to tissues from wild-type littermates. We conclude that
      a mild mutator phenotype arises in the tumors and tissues of cisNf1+/-; p53+/-
      mice, and propose that genomic instability influences NF1 tumor progression and
      disease severity.

PMID- 17208259
TI  - Cortex functional connectivity as a neurophysiological correlate of hypnosis: an
      EEG case study.
AB  - Cortex functional connectivity associated with hypnosis was investigated in a
      single highly hypnotizable subject in a normal baseline condition and under
      neutral hypnosis during two sessions separated by a year. After the hypnotic
      induction, but without further suggestions as compared to the baseline condition,
      all studied parameters of local and remote functional connectivity were
      significantly changed. The significant differences between hypnosis and the
      baseline condition were observable (to different extent) in five studied
      independent frequency bands (delta, theta, alpha, beta, and gamma). The results
      were consistent and stable after 1 year. Based on these findings we conclude that
      alteration in functional connectivity of the brain may be regarded as a neuronal
      correlate of hypnosis (at least in very highly hypnotizable subjects) in which
      separate cognitive modules and subsystems may be temporarily incapable of
      communicating with each other normally.

PMID- 17208260
TI  - Children's and adults' neural bases of verbal and nonverbal 'theory of mind'.
AB  - Theory of mind (ToM) - our ability to predict behaviors of others in terms of
      their underlying intentions - has been examined through verbal and nonverbal
      false-belief (FB) tasks. Previous brain imaging studies of ToM in adults have
      implicated medial prefrontal cortex (mPFC) and temporo-parietal junction (TPJ)
      for adults' ToM ability. To examine age and modality related differences and
      similarities in neural correlates of ToM, we tested 16 adults (18-40 years old)
      and 12 children (8-12 years old) with verbal (story) and nonverbal (cartoon) FB
      tasks, using functional magnetic resonance imaging (fMRI). Both age groups showed
      significant activity in the TPJ bilaterally and right inferior parietal lobule
      (IPL) in a modality-independent manner, indicating that these areas are important
      for ToM during both adulthood and childhood, regardless of modality. We also
      found significant age-related differences in the ToM condition-specific activity
      for the story and cartoon tasks in the left inferior frontal gyrus (IFG) and left
      TPJ. These results suggest that depending on the modality adults may utilize
      different brain regions from children in understanding ToM.

PMID- 17208261
TI  - Prooxidant DNA breakage induced by caffeic acid in human peripheral lymphocytes:
      involvement of endogenous copper and a putative mechanism for anticancer
      properties.
AB  - Plant-derived dietary material contains several classes of polyphenols such as
      flavonoids, curcuminoids, stilbenes and hydroxycinnamic acids. They are
      recognized as naturally occurring antioxidants but also act as prooxidants
      catalyzing cellular DNA degradation in the presence of transition metal ions such
      as copper. Earlier we have shown that the stilbene resveratrol is able to
      mobilize endogenous copper ions leading to oxidative breakage of cellular DNA. In
      this paper, we show that caffeic acid (a hydroxycinnamic acid), which is a major
      constituent of coffee, is also capable of DNA breakage in human peripheral
      lymphocytes. Incubation of lymphocytes with neocuproine inhibited the DNA
      degradation confirming that Cu(I) is an intermediate in the DNA cleavage
      reaction. Further, we have also shown that caffeic acid generates oxidative
      stress in lymphocytes, which is inhibited by scavengers of reactive oxygen
      species and neocuproine. These results are in further support of our hypothesis
      that anticancer mechanism of plant polyphenols involves mobilization of
      endogenous copper, possibly chromatin bound copper, and the consequent prooxidant
      action.

PMID- 17208262
TI  - Differential surface expression of CD18 and CD44 by neutrophils in bone marrow
      and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1
      mice.
AB  - Previously, we have reported that thalidomide (Thd) can enhance neutrophil
      function in female B6C3F1 mice. The present study was intended to evaluate the
      mechanisms underlying the enhanced neutrophil responses following Thd treatment
      intraperitoneally (100 mg/kg) for 14 or 28 days. Treatment with Thd increased the
      numbers of neutrophils in the spleen, peripheral blood, bone marrow, peritoneal
      cavity and lungs of female B6C3F1 mice when compared to the vehicle control mice.
      Thd treatment for 14 days increased the percentage and the number of neutrophils
      in the spleen in the first 8 h (peaking at 2 h) after the last Thd treatment, and
      it returned to the baseline after 24 h. However, Thd treatment for 28 days
      increased the percentage and number of neutrophils in the spleen even at the 24-h
      time point after the last Thd treatment. These neutrophils were demonstrated to
      be functional by the myeloperoxidase activity assay. Further studies have ruled
      out the possibility of an increased bone marrow granulopoiesis following Thd
      treatment. Flow cytometric analysis of the surface expression of adhesion
      molecules suggested that Thd treatment for either 14 or 28 days decreased the
      surface expression of either CD18 or CD44 by bone marrow neutrophils. On the
      other hand, the surface expression of both CD18 and CD44 by splenic neutrophils
      was increased following Thd treatment for 28 days but not for 14 days. No effect
      was produced for other cell surface molecules such as CD62L and CD11a. It was
      possible that decreased surface expressions of CD18 and CD44 facilitated
      neutrophils' release from the bone marrow; increased surface expressions of CD44
      and CD18 by splenic neutrophils after 28 days of Thd treatment increased their
      ability to remain in the periphery. Taken together, Thd treatment increased
      neutrophils in female B6C3F1 mice, at least partially, through differentially
      modulating the surface expression of CD18 and CD44 by the neutrophils in the bone
      marrow and spleen.

PMID- 17208264
TI  - Cytotoxicity of Lachesis muta muta snake (bushmaster) venom and its purified
      basic phospholipase A2 (LmTX-I) in cultured cells.
AB  - Human envenoming by Lachesis muta muta venom, although infrequent, is rather
      severe, being characterized by pronounced local tissue damage and systemic
      dysfunctions. Studies on the pharmacological actions of L. m. muta venom are
      relatively scant and the direct actions of the crude venom and its purified
      phospholipase A(2) (PLA(2)) have not been addressed using in vitro models. In
      this work, we investigated the cytotoxicity of L. m. muta venom and its purified
      PLA(2) isoform LmTX-I in cultured Madin-Darby canine kidney (MDCK) and in a
      skeletal muscle (C2C12) cell lines. As revealed by neutral red dye uptake assay,
      the crude venom (10 or 100 microg/ml) induced a significant decrease in cell
      viability of MDCK cells. LmTX-I at the concentrations tested (70-270 microg/ml or
      5-20 microM) displayed no cytotoxicity in both MDCK and C2C12 cell lines.
      Morphometric analysis of Feulgen nuclear reaction revealed a significant increase
      in chromatin condensation (pyknosis), apparent reduction in the number of mitotic
      nuclei and nuclear fragmentation of some MDCK cells after incubation with L. m.
      muta venom. Monolayer exposure to crude venom resulted in morphological changes
      as assessed by scanning electron microscopy. The staining with TRITC-labelled
      phalloidin showed a marked disarray of the actin stress fiber following L. m.
      muta venom exposure. In contrast, LmTX-I had no effect on nucleus and cell
      morphologies as well as on stress fiber organization. These results indicate that
      L. m. muta venom exerts toxic effects on cultured MDCK cells. The LmTX-I probably
      does not contribute per se to the direct venom cytotoxicity, these effects are
      mediated by metalloproteinases/disintegrins and other components of the venom.

PMID- 17208265
TI  - A combined finite element and modal decomposition method to study the interaction
      of Lamb modes with micro-defects.
AB  - This paper presents a combined finite element and modal decomposition method to
      study the interaction of Lamb waves with damaged area. The finite element mesh is
      used to describe the region around the defects. On the contrary to other hybrid
      models already developed, the interaction between Lamb waves and defects is
      computed in the temporal domain. Then, the modal decomposition method permits to
      determine the wave reflected and transmitted by the damaged area. Modal analysis
      allows also identifying the mode conversions induced by the defects. These
      numerical results agree with previous finite element results concerning the
      interaction of Lamb modes with a notch. Experiments, carried out with gauged
      defects on an aluminum plate, are also compared to numerical predictions to
      validate the simulation. Compared to classical techniques of simulation, this new
      method allows us to investigate the interaction of Lamb modes generated at high
      frequency-thickness product with micro-defects as corrosion pitting.

PMID- 17208263
TI  - Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24): novel
      gene therapeutic for metastatic melanoma.
AB  - A potentially less toxic approach for cancer therapy comprises induction of tumor
      cells to lose growth potential irreversibly and terminally differentiate.
      Combining this scheme termed 'differentiation therapy of cancer' with subtraction
      hybridization to human melanoma cells resulted in the cloning of melanoma
      differentiation associated (mda) genes displaying elevated expression as a
      consequence of induction of terminal differentiation. One originally novel gene,
      mda-7, was found to display elevated expression in normal melanocytes and nevi
      with progressive loss of expression as a consequence of melanoma development and
      progression to metastasis. Based on structure, biochemical properties and
      chromosomal location, mda-7 has now been reclassified as interleukin (IL)-24, a
      member of the expanding IL-10 family of cytokines. In vitro cell culture and in
      vivo animal studies indicate that mda-7/IL-24 selectively induces programmed cell
      death (apoptosis) in multiple human cancers (including melanomas), without
      harming normal cells, and promotes profound anti-tumor activity in nude mice
      containing human tumor xenografts. Based on these remarkable properties, a Phase
      I clinical trial was conducted to test the safety of administration of mda-7/IL
      24 by a replication incompetent adenovirus (Ad.mda-7; INGN 241) in patients with
      advanced solid cancers including melanoma. mda-7/IL-24 was found to be safe and
      to promote significant clinical activity, particularly in the context of patients
      with metastatic melanoma. These results provide an impetus for further clinical
      studies and document a central paradigm of cancer therapy, namely translation of
      basic science from the "bench to the bedside."

PMID- 17208267
TI  - Complete genome sequences of the two viral variants of the Graffi MuLV:
      phylogenetic relationship with other murine leukemia retroviruses.
AB  - A detailed phylogenetic analysis of two variants of the Graffi murine retrovirus,
      GV-1.2 and GV-1.4, showed that they are closely related to SRS 19-6 and Moloney
      MuLVs. Two stretches of sequence testify to the divergence between Graffi and SRS
      19-6 MuLVs, one corresponding to a recombination event of Graffi MuLV with a
      xenotropic virus. Moloney MuLV was found more distant, particularly in the GAG
      region. Our study encompasses every class of MuLVs (ecotropic, amphotropic,
      xenotropic, polytropic) with some focus on exogenous ecotropic viruses and
      further adds to previous phylogenetic studies. Graffi, SRS 19-6, Moloney, Friend
      and Rauscher MuLVs form a cluster that appears to share a common ancestor with
      the Casitas-amphotropic and -ecotropic MuLVs but are more distant to the Akv-type
      and xenotropic MuLVs. The analysis also revealed that the ENV region of HEMV, the
      prototype of the MuLV ancestor, was closely related to the corresponding region
      of Cas-Br-E.

PMID- 17208266
TI  - Thermostabilizing mutations in reovirus outer-capsid protein mu1 selected by heat
      inactivation of infectious subvirion particles.
AB  - The 76-kDa mu1 protein of nonfusogenic mammalian reovirus is a major component of
      the virion outer capsid, which contains 200 mu1 trimers arranged in an incomplete
      T=13 lattice. In virions, mu1 is largely covered by a second major outer-capsid
      protein, sigma3, which limits mu1 conformational mobility. In infectious
      subvirion particles, from which sigma3 has been removed, mu1 is broadly exposed
      on the surface and can be promoted to rearrange into a protease-sensitive and
      hydrophobic conformer, leading to membrane perforation or penetration. In this
      study, mutants that resisted loss of infectivity upon heat inactivation (heat
      resistant mutants) were selected from infectious subvirion particles of reovirus
      strains Type 1 Lang and Type 3 Dearing. All of the mutants were found to have
      mutations in mu1, and the heat-resistance phenotype was mapped to mu1 by both
      recoating and reassortant genetics. Heat-resistant mutants were also resistant to
      rearrangement to the protease-sensitive conformer of mu1, suggesting that heat
      inactivation is associated with mu1 rearrangement, consistent with published
      results. Rate constants of heat inactivation were determined, and the dependence
      of inactivation rate on temperature was consistent with the Arrhenius
      relationship. The Gibbs free energy of activation was calculated with reference
      to transition-state theory and was found to be correlated with the degree of heat
      resistance in each of the analyzed mutants. The mutations are located in upper
      portions of the mu1 trimer, near intersubunit contacts either within or between
      trimers in the viral outer capsid. We propose that the mutants stabilize the
      outer capsid by interfering with unwinding of the mu1 trimer.

PMID- 17208268
TI  - Incorporation of chimeric HIV-SIV-Env and modified HIV-Env proteins into HIV
      pseudovirions.
AB  - Low level incorporation of the viral glycoprotein (Env) into human
      immunodeficiency virus (HIV) particles is a major drawback for vaccine strategies
      against HIV/AIDS in which HIV particles are used as immunogen. Within this study,
      we have examined two strategies aimed at achieving higher levels of Env
      incorporation into non-infectious pseudovirions (PVs). First, we have generated
      chimeric HIV/SIV Env proteins containing the truncated C-terminal tail region of
      simian immunodeficiency virus (SIV)mac239-Env767(stop), which mediates strongly
      increased incorporation of SIV-Env into SIV particles. In a second strategy, we
      have employed a truncated HIV-Env protein (Env-Tr752(N750K)) which we have
      previously demonstrated to be incorporated into HIV virions, generated in
      infected T-cells, to a higher level than that of Wt-HIV-Env. Although the
      chimeric HIV/SIV Env proteins were expressed at the cell surface and induced
      increased levels of cell-cell fusion in comparison to Wt-HIV-Env, they did not
      exhibit increased incorporation into either HIV-PVs or SIV-PVs. Only Env
      Tr752(N750K) exhibited significantly higher (threefold) levels of incorporation
      into HIV-PVs, an improvement, which, although not dramatic, is worthwhile for the
      large-scale preparation of non-infectious PVs for vaccine studies aimed at
      inducing Env humoral responses.

PMID- 17208269
TI  - Disengaging attention sets the temporal limit of attentive tracking.
AB  - At first sight, recent studies investigating the temporal limits of attentive
      tracking show contradictory outcomes. Attentively tracking an object in an
      ambiguous apparent motion display can have an upper limit of around 0.4
      revolutions per second (rps) [Horowitz, T. S., Holcombe, A. O., Wolfe, J. M.,
      Arsenio, H. C., & DiMase, J. S. (2004). Attentional pursuit is faster than
      attentional saccade. Journal of Vision, 4, 585-603] or 1rps [Verstraten, F. A.,
      Cavanagh, P., & Labianca, A. T. (2000). Limits of attentive tracking reveal
      temporal properties of attention. Vision Research, 40, 3651-3664.]. Here, we
      demonstrate that this difference depends on presentation conditions: an important
      determinant for the temporal limit of attentive tracking appears to be the duty
      cycle. Tracking performance at high(er) rates decreases to chance with increasing
      duty cycle, while at low rates duty cycle hardly has an effect on performance.
      Results are discussed in terms of (dis)engagement of attention.

PMID- 17208270
TI  - Seasonal occurrence and toxicity of Microcystis in impoundments of the Huron
      River, Michigan, USA.
AB  - Occurrence and toxicity of Microcystis spp. were measured by ELISA in three
      impoundments of the Huron River in southeast Michigan, USA. Assays were conducted
      weekly from June through October 2005. Additional samples were collected to
      assess microcystin concentrations throughout the drinking water treatment process
      at the Ann Arbor Water Treatment Facility. Water column stability, nutrient
      concentrations, and N:P ratios were examined as potential predictors of
      phycocyanin and microcystin. Microcystin was found in two of the impoundments at
      seasonally varying concentrations. Microcystis presence was associated with N:P
      ratios between 40 and 80 by moles, and toxin levels typically peaked one to two
      weeks after a peak in phycocyanin. The toxin was also detected at low levels at
      all stages of the drinking water treatment process. Freezing and thawing water
      samples prior to analysis yielded maximum microcystin assay concentrations.
      Experiments indicated that the competitive ELISA method is susceptible to false
      negative reporting. This is the first report of algal toxins in this catchment,
      and results demonstrate that sensitive and rapid analytical methods offer the
      chance to link the dynamics of toxin production with environmental conditions.

PMID- 17208271
TI  - Application of food waste disposers and alternate cycles process in small
      decentralized towns: a case study.
AB  - The use of food waste disposers (FWDs) can be an interesting option to integrate
      the management of municipal wastewaters and household organic waste in small
      towns and decentralized areas. This strategy can be even more environmentally
      friendly if a suitable treatment process of the resulting sewage is performed in
      order to control nutrients emission. However, still nowadays, part of the
      scientific and technical community considers the application of this technology a
      possible source of problems. In this study, the FWDs were applied, with a market
      penetration factor of 67%, in a mountain village of 250 inhabitants. Further, the
      existing wastewater treatment plant (WWTP) was upgraded by applying an
      automatically controlled alternate cycles process for the management of nutrients
      removal. With specific reference to the observed results, the impact of the
      ground food waste on the sewerage system did not show particular solids
      sedimentation or significant hydraulic overflows. Further, the WWTP was able to
      face the overloads of 11, 55 and 2g per capita per day of TSS, COD and TN,
      respectively. Then, the increase of the readily biodegradable COD (rbCOD/COD from
      0.20 to 0.25) and the favourable COD/TN ratio (from 9.9 to 12) led to a specific
      denitrification rate of some 0.06kgNO(3)-N/(kg MLVSS day). Therefore, not only
      COD removal, but also the total nitrogen removal increased: the denitrification
      efficiency reached 85%. That led to a better exploitation of the nitrogen-bound
      oxygen and a consequent reduction of energy requirements of 39%. The final
      economic evaluation showed the benefits of the application of this technology
      with a pay back time of 4-5 years.

PMID- 17208272
TI  - Dissolved iron and its speciation in a shallow eutrophic lake and its inflowing
      rivers.
AB  - It has been suggested that iron is a limiting factor on bloom-forming
      cyanobacteria in lake water. Although the availability of iron for phytoplankton
      depends significantly on its speciation, little is known about iron speciation in
      natural lake water. We investigated the horizontal distribution and temporal
      variation of dissolved iron and its chemical speciation in Lake Kasumigaura and
      its two inflowing rivers. Concentrations of dissolved iron and its organic
      ligands, determined by cathodic stripping voltammetry, clearly decreased as lake
      water flowed from the river entry points toward the center of the lake,
      indicating their riverine origin. The fraction of iron occurring in organic
      complexes tended to increase with the water flow. These results suggest that most
      of the dissolved iron in river water forms unstable soluble species, such as
      inorganic iron; thus, these unstable iron species may be scavenged in the mouths
      of rivers, and stable organic complexes of iron may flow to the center of the
      lake. Furthermore, most of the dissolved iron (88.2-99.9%) was present as organic
      complexes, and the inorganic iron level in Lake Kasumigaura (pFe' value=7.8-13.6)
      was similar to that observed in the open ocean. This result suggests that iron is
      an important factor determining the structure of the phytoplankton community in
      Lake Kasumigaura.

PMID- 17208273
TI  - Photochemistry in the mixed aqueous solution of nitrobenzene and nitrous acid as
      initiated by the 355 nm UV light.
AB  - The 355 nm photon-initiated microscopic reaction mechanisms of the mixed aqueous
      solution of nitrobenzene and nitrous acid in the presence or absence of O(2) were
      studied by the laser flash photolysis technique. The main transient absorption
      peaks in the recorded spectra were assigned and the growth/decay trends of
      several transient species were investigated. It was found that the OH radical
      formed from the photolysis of nitrous acid triggered most of the subsequent
      radical reactions. The rate constant of the reaction between OH radical and
      nitrobenzene was measured to be (3.4 +/- 0.1) x 10(9) l mol(-1) s(-1). The
      product from this reaction, namely C(6)H(5)NO(2)-OH adduct, was found to react
      with O(2) to yield C(6)H(5)NO(2)-OHO(2) adduct with a rate constant of (1.6 +/-
      0.2) x 10(9) l mol(-1) s(-1). Final steady-state products were identified by
      GC/MS analysis and were in accordance with the transient spectroscopic results.
      The possible reaction pathways were proposed.

PMID- 17208274
TI  - PCDD/F levels in plasma of a belgian population before and after the 1999 belgian
      PCB/DIOXIN incident.
AB  - We evaluated the impact of the 1999 Belgian dioxin incident on the blood plasma
      polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF)
      levels among 232 Belgian blood donors (74% men, mean age 47 years). The Red Cross
      made plasma samples from before the incident of these donors available. A second
      plasma sample was collected during the second half of 2000. The sum of the 17
      PCDD/F congeners was significantly lower in 2000 compared to 1998 (417 pg/g fat
      versus 445 pg/g fat, respectively). This could be completely attributed to the
      significant decrease of OctaCDD (301 pg/g fat in 2000 versus 277 pg/g fat in
      1998). Moreover a slight but significant decrease was observed for 2,3,7,8
      TetraCDF and for 1,2,3,4,6,7,8-HeptaCDF. 1,2,3,7,8-PentaCDF and 2,3,4,7,8
      PentaCDF however showed a slight but significant increase (respective levels in
      1998 were 0.004 and 14.5 pg/g fat compared to 0.006 and 17.9 pg/g fat in 2000).
      Given their significantly higher presence in incident related food samples this
      increase can be attributed to the food contamination episode. However, the total
      toxicity remained unchanged (22.9 in 1998 versus 23.1 pg WHO-TEQ/g fat, p>0.05).
      Moreover the observed congener profiles and the total PCDD/F levels were similar
      to those of other European non-occupationally exposed populations. In conclusion,
      the 1999 PCB/dioxin incident was traceable in the plasma profiles (rise of the
      two specific PCDF congeners), but comparison of the results for both years
      indicates that the changes were too small to cause an adverse public health
      effect.

PMID- 17208275
TI  - Polybrominated diphenyl ether in sewage sludge in Germany.
AB  - Sewage sludge samples from 11 municipal waste water treatment plants in Germany
      were collected from March 2002 to June 2003. Total Tri- to HpBDE concentrations
      (sum of significant congeners BDE 28, 47, 99, 153, 154 and 183) ranged from 12.5
      to 288 (median 108) and DeBDE (BDE 209) concentrations from 97.1 to 2217 (median
      256) ng/gd.m. BDE 209 dominated the congener profile. A significant change of the
      Tri- to HpBDE congener profile (% of total BDE 28, 47, 99, 153, 154, 183 without
      209) in sludge from different stages of the waste water treatment process
      (primary sludge, secondary excess sludge and (dewatered) digested sludge),
      indicating a degradation of DeBDE to these congeners, was not observed.

PMID- 17208276
TI  - Chlorinated naphthalene formation from the oxidation of dichlorophenols.
AB  - Polychlorinated naphthalenes (PCNs) formed along with dibenzo-p-dioxin and
      dibenzofuran products in the slow combustion of dichlorophenols (DCPs) at 600
      degrees C were identified. Each DCP reactant produced a unique set of PCN
      products. Major PCN congeners observed in the experiments were consistent with
      products predicted from a mechanism involving an intermediate formed by ortho
      ortho carbon coupling of phenoxy radicals; polychlorinated dibenzofurans (PCDFs)
      are formed from the same intermediate. Tautomerization of the intermediate and
      H2O elimination produces PCDFs; alternatively, CO elimination to form
      dihydrofulvalene and fusion produces naphthalenes. Only trace amounts of
      tetrachloronaphthalene congeners were formed, suggesting that the preferred PCN
      formation pathways from chlorinated phenols involve loss of chlorine. 3,4-DCP
      produced the largest yields of PCDF and PCN products with two or more chlorine
      substituents. 2,6-DCP did not produce tri- or tetra-chlorinated PCDF or PCN
      congeners. It did produce 1,8-DCN, however, which could not be explained.

PMID- 17208277
TI  - Effects of filtration and pH perturbation on freshwater organic matter
      fluorescence.
AB  - Fluorescence of organic matter from six contrasting freshwaters was analysed
      after filtration (1.2 microm and 0.2 microm filter sizes) and pH perturbation (+/
      2 pH units from ambient conditions). Two fluorophores were compared in detail:
      tryptophan-like fluorescence, whose filtration and pH characteristics are
      relatively poorly understood, and humic-like fluorescence, which is better
      characterised. Although there was some variability in both fluorophores, the
      tryptophan-like fluorescence showed the most significant decrease in fluorescence
      intensity between raw and 1.2 microm filter samples, and a much smaller decrease
      between 1.2 and 0.2 microm, demonstrating a significant source associated with
      particulate material as well as a significant <0.2 microm fraction. In contrast,
      humic-like fluorescence shows little change with filtration, suggesting that the
      majority of this fluorescence is associated with truly dissolved material. The pH
      perturbation experiments demonstrate that tryptophan-like fluorescence is less
      impacted by pH than with filter fraction. For humic-like fluorescence, pH effects
      are weak and are not as consistent as those reported in the literature for
      extracted humic substances. pH perturbation of the freshwaters shows a wide range
      of sample specific pH responses, significantly more variable than that observed
      in experiments using extracted humic substances and tryptophan standards,
      demonstrating the natural variability of freshwater dissolved organic matter.

PMID- 17208278
TI  - A rapid, sensitive screening test for polycyclic aromatic hydrocarbons applied to
      Antarctic water.
AB  - We describe a rapid, sensitive, fluorescence screening test for polycyclic
      aromatic hydrocarbons in water samples that avoids more costly time-consuming
      methods. The screening test works by detecting benzo[a]pyrene. It runs without
      the need for any pre-concentration step, thus rendering it suitable for routine
      use in water-quality-control laboratories. The test recognizes contaminated
      samples rapidly (150 s) and inexpensively with a cut-off level of 10 ng l(-1),
      which is the value that the European Union and World Health Organization (WHO)
      have laid down in its assessment of the quality of water for human consumption.
      This was first ascertained by analysing tap and waste-water samples before
      studying environmental water samples from the Antarctic region. The reliability
      of the screening test was 2% false positives and 4% false negatives in 200
      samples of tap and waste-water. The applicability was confirmed by the fact that
      the predictions of the screening test coincided exactly with results obtained
      with gas chromatography-mass spectrometry assays. We also discuss the polluted
      Antarctic samples and the possible sources of the contamination involved.

PMID- 17208279
TI  - Multivariate data analysis of pollutant profiles: PCB levels across Europe.
AB  - It is not always recognised that standard multivariate analyses applied to
      pollution profile data (i.e. where data are relative amounts of pollutants
      expressed as proportions of their total) give rise to problems in the analysis
      and interpretation of results: a simple solution is to carry out analyses on log
      ratios of proportions. However, while solving many problems, this approach is
      very sensitive to the issue of values below detection limits. These approaches
      have been applied to a dataset of the levels of 29 PCB congeners in ambient air
      samples across Europe during the summer of 2002. Multivariate descriptive methods
      (principal component analysis and cluster analysis) and inferential techniques
      (multivariate ANOVA, multiple linear and logistic regression) and graphical tools
      (2D and 3D plots, principal components plots, biplots and triangular diagrams)
      were used to analyse the proportions of five PCB homologues (tri-hepta). These
      established that there was considerable difference in the pollution profiles of
      the 71 samples: the greatest variation was between samples with differing ratios
      of tri-hexa and tri-hepta PCB homologues, and the samples showed little sign of
      consistent clusters. There was a significant difference between typical profiles
      from rural and urban areas such that urban samples (and those with high total
      PCBs) had higher proportions of tetra- and tri-PCBs compared to hexa- and hepta
      PCBs.

PMID- 17208280
TI  - Advanced oxidation processes for the treatment of olive-oil mills wastewater.
AB  - In this work, the treatment of an actual industrial waste with three advanced
      oxidation processes (AOP) has been studied: conductive-diamond electrooxidation
      (CDEO), ozonation and Fenton oxidation. The wastewater comes from olive-oil mills
      (OMW) and contains a COD of nearly 3000 mg dm(-3). CDEO allowed achieving the
      complete mineralization of the waste with high current efficiencies. Likewise,
      both ozonation and Fenton oxidation were able to treat the wastes, but they
      obtained very different results in terms of efficiency and mineralization. The
      accumulation of oxidation-refractory compounds as final products excludes the use
      of ozonation and Fenton oxidation as a sole treatment technology. This confirms
      that besides the hydroxyl-radical mediated oxidation, CDEO combines other
      important oxidation processes such as the direct electro-oxidation on the diamond
      surface and the oxidation mediated by other electrochemically formed compounds
      generated on this electrode.

PMID- 17208281
TI  - Monitoring of ambient air PCDD/F levels in Portugal.
AB  - As part of a monitoring program conducted by IDAD--Institute for Environment and
      Development and supported by regional municipal solid waste (MSW) management
      authorities, dioxin concentrations in ambient air were measured in three regions
      of Portugal: Porto, Lisbon and Madeira. These independent studies were performed
      with the intention of providing data as a basis for the evaluation of potential
      impacts of the operation of recently built MSW incinerators. Thus, 170 samples
      were collected in nine different sites from January 1999 till present. The
      measured levels revealed an extremely variable content of PCDDs/PCDFs depending
      both on the area and the season of the year. Samples taken in Porto and Lisbon
      reveal a similar homologue structure even if concentrations measured in the Porto
      region are significantly greater. Data from Madeira is characteristic of a remote
      site with some of the congeners concentrations below the detection limit.

PMID- 17208282
TI  - Influence of start-up on PCDD/F emission of incinerators.
AB  - This study aims to evaluate the influence of start-up on polychlorinated dibenzo
      p-dioxins and polychlorinated dibenzofurans (PCDD/Fs) concentration in the stack
      flue gas of incinerators and its contributing PCDD/F emission. The PCDD/F
      emission of the first sample among three consecutive stack flue gas samples of
      five intermittent incinerators, which sampled at a stable combustion condition
      after start-up, is 2-3 times higher than the mean of the others. For verifying
      the PCDD/F characteristics of incinerators during start-up, one continuous MSWI
      was investigated for two years. The elevated PCDD/F emissions of the MSWI during
      start-up could reach 96.9 ng I-TEQN m(-3) and still maintained a high PCDD/F
      emission (40 times higher than the Taiwan emission limit) even 18 h after the
      injection of activated carbon, indicating the memory effect. Taking the MSWI for
      example, which consists of four incinerators, the estimated annual PCDD/F
      emission from normal operational conditions was 0.112 g I-TEQ. However, one start
      up procedure can generate approximately 60% of the PCDD/F emissions for one whole
      year of normal operations. And the PCDD/F emission, which is the result of the
      start-ups of four incinerators, was at least two times larger than that of a
      whole year's normal operations, without consideration for the PCDD/F emission
      contributed by the long lasting memory effect.

PMID- 17208283
TI  - The influence of soil contamination on the concentrations of PCBs in milk in
      Siberia.
AB  - Although atmospheric deposition is generally the dominant pathway of PCBs into
      agricultural food chains, soil ingestion by livestock can be important in some
      cases. The relationship between PCB levels in cow's milk and in pasture soil was
      studied in the Irkutsk region in Siberia where an historical atmospheric
      source(s) of PCBs has led to widespread contamination of soil. Milk samples were
      collected in spring and again in autumn from 18 different farms and analyzed for
      PCBs. Pasture soil samples were also collected and analyzed. The PCB
      concentrations in both milk and soil ranged over more than an order of magnitude
      between the farms. A good correlation was obtained between PCB levels in autumn
      milk and in soil. This together with a range of other evidence suggested that
      ingestion of pasture soil was the dominant source of the PCB contamination in the
      milk. The average soil ingestion rate was estimated to be 1700 g/d, which is at
      the upper end of values reported in the literature. This may be due to the arid
      summer climate or the animal husbandry practices in Siberia.

PMID- 17208284
TI  - Clinical use of combined positron emission tomography and computed tomography
      (FDG-PET/CT) in recurrent ovarian cancer.
AB  - OBJECTIVE: The aim of this study was to evaluate the use of co-registered PET/CT
      using F-18 fluorodeoxyglucose (FDG) for surveillance and follow-up of ovarian
      cancer patients to detect recurrent disease. MATERIAL AND METHODS: A
      retrospective chart review was performed on 39 ovarian cancer patients who
      underwent a total of 59 FDG-PET/CT scans. The following information was obtained:
      clinical indication for FDG-PET/CT, the results of FDG-PET/CT particularly with
      regard to the additional diagnostic information, the localization of disease and
      subsequent clinical patient management. RESULTS: Twenty-four FDG-PET/CT were
      performed in 22 patients with previously negative or indeterminate CT scans but
      rising CA-125 levels providing a sensitivity of 90% for localizing disease. Nine
      FDG-PET/CT in 8 patients with clinical symptoms of recurrence but normal CA-125
      levels detected all three patients who had recurrent disease confirmed within 6
      months of follow-up. In addition, 4 FDG-PET/CT performed as routine follow-up
      with no clinical evidence of recurrent disease were true-negative in all cases.
      Fourteen FDG-PET/CT in 12 patients with recurrent disease already identified by
      conventional CT imaging were useful in guiding treatment decisions such as
      radiation therapy, surgery or chemotherapy by confirming the recurrence and more
      precisely localizing the site(s) of disease. Of note, FDG-PET/CT helped to avoid
      surgery in four patients who had additional disease detected in unresectable
      anatomic areas. A total of 51 FDG-PET/CT were performed in the patients described
      above with an overall sensitivity and specificity of 94.5% and 100%,
      respectively. Eight FDG-PET/CT scans in five patients performed for assessment of
      treatment response following chemotherapy or radiation were useful as the disease
      was not clearly visualized by conventional CT imaging at baseline. CONCLUSIONS:
      In our experience, FDG-PET/CT has the greatest utility in settings of suspected
      ovarian cancer recurrence, particularly in patients with rising CA-125 levels and
      negative conventional imaging. FDG-PET/CT was specifically helpful in optimizing
      the selection of patients for site-specific treatment, including radiation
      treatment planning, and aided in the selection of optimal surgical candidates.
      The co-registered metabolic-anatomic information from combined FDG-PET/CT holds
      promise in replacing the single imaging procedures.

PMID- 17208286
TI  - Effects of gamma-hydroxybutyric acid and flunitrazepam on ethanol intake in male
      rats.
AB  - Both gamma-hydroxybutyric acid (GHB) and flunitrazepam are often used illicitly
      in combination with ethanol. Nevertheless, the effects that these and other drugs
      of abuse have on the reinforcing effects of ethanol remain inconclusive. To test
      the effects of GHB and flunitrazepam on contingent ethanol intake, twelve male
      Long-Evans rats were trained to orally consume ethanol using a saccharin-fading
      procedure. After training, all animals preferentially consumed ethanol instead of
      water at each of five ethanol concentrations (0-32%) when tested with a two
      bottle preference test in the homecage. Animals then received a noncontingent
      dose of ethanol (0.32, 0.56, 1, and 1.33 g/kg), flunitrazepam (0.032, 0.1, and
      0.32 mg/kg), or GHB (100, 180, 320, and 560 mg/kg) prior to each subject's daily
      access to ethanol (18% v/v). Noncontingent doses of ethanol decreased ethanol
      intake, however, the subjects consumed enough ethanol to maintain a consistent
      total ethanol dose in g/kg. Flunitrazepam did not affect ethanol intake at any
      dose tested, whereas GHB only affected intake at the highest dose (560 mg/kg), a
      dose that also produced sedation. These data suggest that there are perceptible
      or qualitative differences between GHB, flunitrazepam, and ethanol in terms of
      their capacity for modulating oral ethanol intake in outbred rats.

PMID- 17208285
TI  - Delay aversion: effects of 7-OH-DPAT, 5-HT1A/1B-receptor stimulation and D
      cycloserine.
AB  - Impulsive individuals often display an aversion to waiting for rewards. Delay
      aversion can be quantified in rats in a delayed reward task, in which animals
      choose between an immediately available, small reward, and a large reward
      available after a delay. In previous research conducted at our laboratory and in
      literature, positive correlations between delay aversion and aggression,
      substance abuse and persistence during extinction of conditioned responses were
      found. The correlations suggest a possible shared pharmacology. Therefore, we
      tested drugs with known effects on these behaviors for possible effects on delay
      aversion: the dopamine D(3)-receptor agonist 7-OH-DPAT, the 5-HT(1A)-receptor
      agonist flesinoxan, the 5HT(1A/1B)-receptor agonist eltoprazine, and the NMDA
      receptor agonist d-cycloserine. The results show that 7-OH-DPAT slightly
      decreased choice for the large reward. Flesinoxan disrupted task execution by
      lowering choice for the large reward even at a delay of 0 s. Eltoprazine slightly
      increased choice for the large reward, but the 5-HT(1B)-antagonist GR127935 had
      no effect. Administration of D-cycloserine also had no effect on choice behavior.
      The data suggest the dopamine D(3)-receptor and the 5-HT(1B)-receptor are
      interesting targets for treating delay aversion impulsivity. These targets were
      correctly predicted by the positive correlation between delay aversion and
      aggressive behavior and the intimate links between delay aversion and substance
      abuse disorders.

PMID- 17208287
TI  - TNF polymorphism and bronchoalveolar lavage cell TNF-alpha levels in chronic
      beryllium disease and beryllium sensitization.
AB  - BACKGROUND: Beryllium stimulates TNF-alpha from chronic beryllium disease (CBD)
      bronchoalveolar lavage (BAL) cells. OBJECTIVE: We sought to relate TNF
      polymorphisms to beryllium-stimulated TNF-alpha production, to the development of
      CBD, and to the risk of more severe CBD over time. METHODS: We recruited 147
      patients with CBD, 112 beryllium-sensitized subjects, and 323 control subjects;
      genotyped 5 TNF promoter polymorphisms; and measured beryllium-stimulated and
      unstimulated BAL cell TNF-alpha production from a subset of subjects. RESULTS:
      Beryllium-stimulated, but not beryllium-unstimulated, BAL cell TNF-alpha
      production was significantly increased in patients with CBD compared with that
      seen in those only sensitized (P = .0002). Those subjects with the TNF -857T
      allele and the only haplotype (haplotype 4) containing this allele demonstrated
      significantly lower unstimulated BAL cell TNF-alpha production compared with that
      seen in noncarriers (P = .009). Patients with CBD alone and combined with
      sensitized subjects carrying the TNF haplotype 1 compared with those without this
      haplotype had significantly increased beryllium-stimulated BAL cell TNF-alpha
      levels (P = .02). We found no significant association between patients with CBD,
      sensitized subjects, and control subjects with any of the TNF promoter
      polymorphisms or haplotypes. A greater decrease in Pao(2) at maximum exercise was
      noted in patients with CBD with the -1031C allele (P = .03) and with haplotypes
      other than the TNF haplotype 1 (P = .01), 3 (from 5) of which contain the -1031C
      allele. CONCLUSIONS: The -857T allele and haplotype 1 are associated with BAL
      cell TNF-alpha production, indicating a potential role of TNF promoter variants
      in regulation of TNF production in sensitized subjects and patients with CBD.
      CLINICAL IMPLICATIONS: TNF promoter variants are not risk factors for CBD or
      sensitization.

PMID- 17208288
TI  - Excessive body weight is associated with additional loss of quality of life in
      children with asthma.
AB  - BACKGROUND: Asthma and excessive body weight frequently coexist, whereas the
      exact relationship between the 2 diseases is unknown. OBJECTIVE: To study whether
      asthma combined with excessive body weight has a greater effect on quality of
      life in children than the separate effects of asthma or excessive body weight
      alone. METHODS: In a cross-sectional design, 1758 school children (age 7-10
      years) participated: 4 study groups were composed of children with asthma and
      with/without excessive body weight, and healthy controls with/without excessive
      body weight. Diagnosis of asthma was defined by either a doctor's diagnosis or by
      core questions of the International Study of Asthma and Allergies in Childhood
      questionnaire in combination with either reversible airway obstruction or
      bronchial hyperresponsiveness. Excessive body weight was defined by using
      international cutoff points for body mass index. Quality of life was evaluated by
      the Pediatric Asthma Quality of Life Questionnaire. RESULTS: For all domains of
      quality of life, children with both asthma and excessive body weight had lower
      scores than children with either asthma alone or excessive body weight alone.
      Compared with healthy controls, the score was 25% lower in children with asthma
      and excessive body weight, 14% lower in children with asthma and normal weight,
      and only 1% lower in overweight controls. CONCLUSION: Excessive body weight is
      associated with an additional decrease in quality of life in children with
      asthma. CLINICAL IMPLICATIONS: Clinicians should be aware of the interaction
      between asthma and excessive body weight and the effect on quality of life and
      should give extra attention to children with both conditions.

PMID- 17208289
TI  - Association between leisure-time physical activity and health-related quality of
      life changes over time.
AB  - OBJECTIVE: This study aimed to assess whether changes in leisure-time physical
      activity over 3 years are associated with changes in health-related quality of
      life. METHOD: Among the adults enrolled in the Supplementation en Vitamines et
      Mineraux Antioxidants study in France, 3891 completed the Modifiable Activity
      Questionnaire to assess leisure-time physical activity and the Medical Outcomes
      Study 36-item Short-Form to assess health-related quality of life in 1998 and
      2001. Multivariate analyses involving logistic and linear regressions determined
      the association between changes in leisure-time physical activity and changes in
      health-related quality of life. RESULTS: Over 3 years, increased leisure-time
      physical activity was associated with high scores in health-related quality of
      life dimensions: physical functioning, mental health, vitality for both sexes as
      well as social functioning for women only. An increase of 1 h per week of leisure
      time physical activity was associated with a 0.17- and 0.39-point increase in the
      vitality dimension in men and women, respectively. The mental component score was
      also increased in women increasing their leisure-time physical activity.
      CONCLUSION: The long-term association between leisure-time physical activity and
      health-related quality of life changes is limited and has little clinical
      significance, especially for men and for the physical health-related quality of
      life dimensions. The long-term association needs to be further explored before
      formulating public health recommendations.

PMID- 17208290
TI  - The effectiveness of the stereomicroscopic evaluation of embryo quality in
      vitrified-warmed porcine blastocysts: an ultrastructural and cell death study.
AB  - The objective of this study was to analyze the validity of the stereomicroscopic
      evaluation of vitrified-warmed (V-W) porcine blastocysts. Unhatched blastocysts
      were obtained from Large-white gilts (n=10). Blastocysts (n=156) were vitrified
      using the Open Pulled Straw technology. After warming, V-W blastocysts were
      cultured for 24h (V24). Then, their developmental progression was morphologically
      assessed by stereomicroscopy and classified as: V24 viable re-expanded
      blastocysts; V24 viable hatched blastocysts or V24 degenerated. Blastocysts which
      re-expanded or hatched after warming were considered viable. Some fresh
      blastocysts were not vitrified and were evaluated after 24h in culture (F24). By
      stereomicroscopic analysis all the fresh blastocysts were considered viable. Some
      F24, V24 re-expanded viable, V24 hatched viable and V24 degenerated blastocysts
      were processed for transmission electron microscopy (n=13, 19, 9 and 9,
      respectively) or assessed by TUNEL for cell-death evaluation (n=16, 21, 11 and
      21, respectively). All V24 hatched blastocysts showed similar ultrastructure to
      fresh blastocysts. However, some V24 re-expanded blastocysts considered viable
      (6/19) revealed ultrastructural alterations. Degenerated V24 blastocysts showed
      ultrastructural disintegration. Hatched V24 blastocysts did not differ (p>0.05)
      from F24 hatched blastocysts with regard to the ratio of dead cells (2.8+/-0.5%
      versus 1.9+/-0.3%, respectively). However, V24 expanded blastocysts had higher
      (p<0.01) cell death levels (4.3+/-3.4%) than those observed in the F24 expanded
      blastocysts (1.1+/-0.3%). The degenerated blastocysts showed the highest cell
      death index (19.4+/-6.3%). In summary, V-W blastocyst hatching during in vitro
      culture appears to coincide with good ultrastructure and low cell-death index,
      suggesting that the hatching rate assessed by stereomicroscopy is more
      appropriate than embryo re-expansion for an evaluation of V-W blastocyst quality.

PMID- 17208291
TI  - Cytoplasmic glutathione regulated by cumulus cells during porcine oocyte
      maturation affects fertilization and embryonic development in vitro.
AB  - It is generally accepted that cumulus cells support the nuclear maturation of
      mammalian oocytes. In the present study, we examined relationships between the
      cytoplasmic glutathione (GSH) content of porcine oocytes, and oocyte nuclear
      maturation, fertilization or subsequent embryonic development. Cumulus-oocyte
      complexes (COCs; control group) and oocytes denuded of cumulus cells after
      collection (DO 0h group) were cultured for 24h with dibutyryl cAMP, eCG and hCG
      (first culture step) and then for a further 20h without supplements (second
      culture step; 44h total culture). After the first culture step, some of the COCs
      were denuded, either completely (DO 24h group) or partly (H-DO 24h group), and
      then matured by the second culture step. Also, in the second culture step, some
      DOs were co-cultured with cumulus cells that had been pre-cultured for 24h (DO
      24h+CC group). The maturation rates of all the cumulus-removed groups (DO 0h, DO
      24h, H-DO 24h and DO 24h+CC groups) were lower (34.3-45.0%) than that of the
      control group (64.5%; P<0.05). The GSH contents of matured oocytes in the
      completely denuded groups (DO 0h, DO 24h and DO 24h+CC groups) were lower (4.03
      5.26pmol/oocyte) than that of the control group (9.60pmol/oocyte; P<0.05);
      however, the H-DO 24h group had an intermediate value (7.0pmol/oocyte). The male
      pronuclear formation rates of completely denuded oocytes were lower (41.4-59.3%)
      than that of the control group (89.4%; P<0.05), whereas the H-DO 24h group had an
      intermediate rate (80.0%). The blastocyst formation rates of the completely
      denuded oocytes were lower (3.0-4.5%) than that of the control group (19.9%;
      P<0.05), and the H-DO 24h group again had an intermediate rate (11.6%). The GSH
      content was correlated with the rates of male pronuclear formation (P<0.01) and
      blastocyst formation (P<0.01), and also with the number of cells per blastocyst
      (P<0.01). In conclusion, we inferred that GSH synthesized by intact cumulus cells
      during maturation culture improved oocyte maturation and played an important role
      in fertilization and embryonic development.

PMID- 17208292
TI  - Bacterial accumulation by Branchiomma luctuosum (Annelida: Polychaeta): a tool
      for biomonitoring marine systems and restoring polluted waters.
AB  - In this study, we examined the bacterial accumulation in the filter feeder
      polychaete Branchiomma luctuosumGrube (Sabellidae). Analyses were performed on
      worm homogenates from 'unstarved' and 'starved' individuals, and seawater from
      the same sampling site (Gulf of Taranto, Western Mediterranean, Italy). Densities
      of culturable heterotrophic bacteria (22 degrees C), total culturable bacteria at
      37 degrees C and halophilic vibrios at 22 and 35 degrees C were measured on
      Marine Agar 2216, Plate Count Agar and thiosulphate-citrate-bile-salt-agar (TCBS)
      plus 2% NaCl, respectively. Total and faecal coliforms as well as faecal
      streptococci were determined by the Most Probable Number method. Results showed
      that B. luctuosum is able to accumulate all the considered six microbiological
      groups with a higher efficiency for autochthonous bacteria. The analysis also
      indicated that bacterial groups differ in their resistance to digestion by B.
      luctuosum. Our data suggest the potential role of B. luctuosum as an useful
      bioindicator to assess low levels of microbiological water pollution as well as
      bioremediator of microbial polluted waters.

PMID- 17208293
TI  - Catalytic activity of acetylcholinesterase immobilized on mesoporous molecular
      sieves.
AB  - MCM-41 and FSM-16 were used for enzyme immobilization on account of their good
      physical and chemical properties. In this work, the catalytic activity of
      acetylcholinesterase (AChE) immobilized on these materials was investigated,
      using neostigmina as AChE inhibitor. The results show that AChE was adsorbed on
      MCM-41 and on FSM-16-TIPB. AChE immobilized on the latter material maintained 70%
      of its activity and the material did not hydrolyze ACh (as MCM-41) by itself.
      Therefore, FSM-16-TIPB was the best material, considering also that when
      neostigmine was applied to AChE immobilized on FSM-16-TIPB, the activity of AChE
      decreased as occurs in its free from. Hence, this model could be useful in the
      evaluation of different kinds of AChE inhibitors, allowing the recycling of
      enzymes and making possible several assays and thereby, lowering cost.

PMID- 17208294
TI  - High-loading nanosized micelles of copoly(styrene-maleic acid)-zinc
      protoporphyrin for targeted delivery of a potent heme oxygenase inhibitor.
AB  - Amphiphilic styrene-maleic acid (SMA) copolymer efficiently formed micelles with
      a potent heme oxygenase inhibitor-zinc protoporphyrin (ZnPP). The micelles were
      constructed by subtle pH adjustments to form non-covalent interaction between the
      hydrophobic ZnPP and amphiphilic SMA. The micelles (SMA-ZnPP) thus formed were
      nanoparticles with narrow size distribution in water (mean diameter 176.5nm),
      having tunable loading (from 15% to 60% w/w of ZnPP) with remarkable aqueous
      solubility. SMA-ZnPP had an average molecular size of 144kDa as determined by
      size-exclusion chromatography (SEC), this size is a marked increase from the
      molecular weight of free ZnPP (626.03Da), suggesting the formation of micellar
      structure. The micelles showed a constant ZnPP release rate of about 0.5%/day in
      vitro at neutral pH. SMA-ZnPP micelles inhibited splenic microsomal HO-1
      activity, in a competitive and dose-dependent manner, with an apparent inhibitory
      constant (K(i)) of 0.12mum, comparable to free ZnPP and also exhibited marked
      cytotoxic effect on KYSE-510 human esophageal cancer cells. The unique features
      of SMA-ZnPP micelles are that they are nanoparticles in aqueous solution having
      high water solubility and loading, yet macromolecular in nature, which can be
      beneficial in targeted release of a potent HO-1 inhibitor.

PMID- 17208295
TI  - Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic
      protein-2 and human mesenchymal stem cells.
AB  - Acrylated hyaluronic acid (HA) was used as a scaffold for bone morphogenic
      protein-2 (BMP-2) and human mesenchymal stem cells (hMSCs) for rat calvarial
      defect regeneration. HA was acrylated by two-step reactions: (1) introduction of
      an amine group using adipic acid dihydrazide (ADH); (2) acrylation by N
      acryloxysuccinimide. Tetrathiolated poly(ethylene) glycol (PEG-SH(4)) was used as
      a cross-linker by a Michael-type addition reaction and the hydrogel was formed
      within 10min under physiological conditions. This hydrogel is degraded completely
      by 100U/ml hyaluronidase in vitro. hMSCs and/or BMP-2 was added during gelation.
      Cellular viability in vitro was increased up to 55% in the hydrogels with BMP-2
      compared with the control. For in vivo calvarial defect regeneration, five
      different samples (i.e., control, hydrogel, hydrogel with BMP-2, hydrogel with
      MSCs, and hydrogel with BMP-2 and MSCs) were implanted for 4 weeks. The
      histological results demonstrated that the hydrogels with BMP-2 and MSCs had the
      highest expression of osteocalcin and mature bone formation with vascular
      markers, such as CD31 and vascular endothelial growth factors, compared with the
      other samples. This study demonstrated that HA base hydrogel can be used for cell
      and growth factor carriers for tissue regeneration.

PMID- 17208296
TI  - Diurnal and seasonal variation of cholecystokinin peptides in humans.
AB  - Cholecystokinin (CCK) was determined in plasma obtained from 10 female (aged
      23.4+/-SD 2.3 years) and nine male (aged 22.0+/-SD 1.4 years) healthy volunteers.
      Blood samples were drawn three times (8.00a.m., 12 noon and 8.00a.m.) on each of
      two sessions, one in the winter (November-December) and one in the summer (April
      July). The participants had fasted (and were nicotine-free) since midnight
      preceding the sampling. A standardized breakfast was served after the first
      sampling. CCK was determined by radioimmunoassay. The area under the curve 0-24h
      (AUC)(CCK Winter) was lower than AUC(CCK Summer) (F(1:17)=4.73; P=0.0440) in the
      whole group of volunteers. On comparing the CCK concentrations within each
      session, there was an overall difference in winter (F(2:36)=14.81; P<0.0001) as
      well in summer (F(2:36)=18.39; P<0.0001). Post hoc comparisons yielded a
      difference between the 8.00a.m. and 12 noon concentrations on the first day in
      winter (t=-3.96; P=0.0009) as well as in summer (t=-4.64; P=0.0002). The
      difference between the summer and winter AUCs(CCK) correlated with the difference
      between AUCs for temperatures in summer and winter (r=0.58; P=0.0089). The
      correlation was accounted for by the females (r=0.73; P=0.0171). The results are
      in accord with a diurnal and a seasonal variation of CCK in human plasma.

PMID- 17208297
TI  - BCR-ABL mutant kinetics in CML patients treated with dasatinib.
AB  - Dasatinib is efficient in vitro against most of CML cells harboring ABL kinase
      domain mutations and induces high rates of response in imatinib-resistant CML
      patients. Here, we monitored the mutated BCR-ABL transcripts during the follow-up
      of 12 CML patients treated with dasatinib. We identified four groups of patients
      based on their sensitivity to dasatinib. Clinical responses were correlated to
      the in vitro sensitivity of BCR-ABL mutants to dasatinib, however, some
      discrepancies were observed in a subfraction of CML patients, suggesting subtle
      differences between in vitro observations and clinical entities and/or the onset
      of other mechanisms responsible for dasatinib resistance.

PMID- 17208298
TI  - The health and well-being of neglected, abused and exploited children: the Kyiv
      Street Children Project.
AB  - OBJECTIVE: To report on the backgrounds and physical and emotional well-being of
      street children using two street shelters in Kyiv, Ukraine. This study is
      important because personal accounts of street children may highlight individual
      or family factors that are associated with vulnerability for and risk of poor
      mental health, and these could have serious repercussions for the future. This
      study also poses a challenge to research because street children are a highly
      elusive population that services find hard to reach. METHODS: Ninety-seven
      children were recruited and interviewed using a semistructured, psychosocial
      interview schedule; psychopathology was measured using the Strengths and
      Difficulties Questionnaire (SDQ) and the Mood and Feelings Questionnaire (MFQ).
      RESULTS: Seventy percent of street children scored for behavioral and emotional
      difficulties on the SDQ, and 74% scored for depression on the MFQ. Current health
      problems were reported by 78%, with 43% described as persistent or severe. Two
      thirds of the children in this sample were not homeless but had chosen life on
      the streets in preference to permanent residence with their families. Their
      "survival" history on the streets contributed to the development of three
      different profiles of vulnerability. CONCLUSIONS: High rates of physical and
      emotional problems in a population of street children, many of whom were still
      connected to their families, emphasize the importance of developing different
      approaches for children with different vulnerabilities. This study also
      demonstrates the feasibility of embedding on-going field research into the
      service dimension of "front-line" social care agencies.

PMID- 17208300
TI  - Tissue-specific expression and molecular modeling of cytosolic manganese
      superoxide dismutases from the white shrimp Litopenaeus vannamei.
AB  - Manganese superoxide dismutases (MnSODs) are usually mitochondrial enzymes,
      although there are few examples of cytosolic MnSODs (cMnSOD). We have previously
      characterized a cMnSOD cDNA from Litopenaeus vannamei hemocytes, and to obtain
      new insights into the tissue specific expression and the protein structure, we
      characterized three more different cMnSOD transcripts (cMnsod1, cMnsod2 and
      cMnsod3) and modeled the three-dimensional protein structure using human MnSOD as
      a template. The nucleotide sequences differ in seven positions. Four differences
      are silent; while three produce changes in amino acid sequence. cMnsod1, cMnsod2
      and cMnsod3 are differentially expressed in nervous system, hepatopancreas and
      hemocytes. The structural protein model predicts bona fide MnSODs with proper
      coordination for the enzymatic activity.

PMID- 17208299
TI  - Biomphalaria glabrata transcriptome: identification of cell-signalling,
      transcriptional control and immune-related genes from open reading frame
      expressed sequence tags (ORESTES).
AB  - Biomphalaria glabrata is the major intermediate snail host for Schistosoma
      mansoni, one of the important schistosomes infecting man. Much remains to be
      discovered concerning specific molecules mediating the defence events in these
      intermediate hosts, triggered by invading schistosomes. An expressed sequence tag
      (EST) gene discovery strategy known as ORESTES has been employed to identify
      transcripts that might be involved in snail-schistosome interactions in order to
      examine gene expression patterns in infected B. glabrata. Over 3930 ESTs were
      sequenced from cDNA libraries made from both schistosome-exposed and unexposed
      snails using different tissue types, producing a database of 1843 non-redundant
      clones. The non-redundant set has been assessed for gene ontology and KEGG
      pathway assignments. This approach has revealed a number of signalling,
      antioxidant and immune-related gene homologues that, based on current
      understanding of molluscan and other comparative systems, might play an important
      role in the molluscan defence response towards infection.

PMID- 17208301
TI  - Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease.
AB  - The complexity of multicellular organisms is dependent on systems enabling cells
      to respond to specific stimuli. Cytokines and their receptors are one such
      system, whose perturbation can lead to a variety of disease states. This review
      represents an overview of our current understanding of the cytokine receptors,
      Janus kinases (Jaks), Signal transducers and activators of transcription (Stats)
      and Suppressors of cytokine signaling (Socs), focussing on their contribution to
      diseases of an immune or hematologic nature.

PMID- 17208303
TI  - Posterior vitreous detachment and retinal detachment after cataract surgery.
AB  - OBJECTIVE: To evaluate possible changes of vitreous status in emmetropic eyes
      after uneventful phacoemulsification surgery, and possible related complications
      such as the onset of retinal detachment (RD). DESIGN: Retrospective case series.
      PARTICIPANTS: Four hundred fifty-three emmetropic eyes from 453 patients (mean
      age, 62.03+/-5.57 years) subjected to uneventful phacoemulsification with
      intraocular lens implantation in the capsular bag were considered in the study.
      They had a refractive error within +/-0.5 diopters (mean, -0.21+/-0.08). Eyes
      with peripheral retinal lattice degeneration were included only if asymptomatic
      and only if the degeneration involved one retinal quadrant. After cataract
      surgery, the 453 eyes were evaluated preoperatively at days 1, 15, and 30 and
      months 3, 6, 12, 18, 24, 36, 48, and 60. The whole period of follow-up was 5
      years. METHODS: Evaluation of vitreous status by biomicroscopic examination,
      indirect binocular ophthalmoscopy, and B-scan ultrasonography. MAIN OUTCOME
      MEASURES: Postoperative onset of posterior vitreous detachment (PVD) and RD.
      RESULTS: After cataract surgery, a PVD occurred in 107 of 141 (75.88%) eyes
      without preoperative PVD or lattice degeneration. Posterior vitreous detachment
      occurred in 41 of 47 eyes (87.23%) with preoperative lattice degeneration and no
      PVD. Eyes with preoperative lattice degeneration and postoperative PVD showed a
      higher incidence of RD after cataract surgery (21.27%) than eyes without
      preoperative PVD or lattice degeneration (0.70%). In all patients with lattice
      degeneration, RD originated from horseshoe retinal tears on lattice areas located
      on the superior quadrants. No correlation was observed between the development of
      RD and age. CONCLUSIONS: Our results suggest that the onset of postoperative PVD
      should be considered an important risk factor for the development of RD after
      cataract surgery, particularly in eyes with lattice areas.

PMID- 17208304
TI  - Synthesis, characterization and assessment of the cytotoxic properties of cis and
      trans-[Pd(L)(2)Cl(2)] complexes involving 6-benzylamino-9-isopropylpurine
      derivatives.
AB  - A series of square-planar Pd(II) complexes of the composition cis
      [Pd(L(n))(2)Cl(2)] {L(1)=2-chloro-6-benzylamino-9-isopropylpurine (1), L(2)=2
      chloro-6-[(4-methoxybenzyl)amino]-9-isopropylpurine (2), L(3)=2-chloro-6-[(2
      methoxybenzyl)amino]-9-isopropylpurine (3) and 2-[(chloropropyl)amino]-6
      benzylamino-9-isopropylpurine (6)} has been synthesized by the reaction of
      PdCl(2) with L(n) in a 1:2 molar ratio. In contrast, the same reaction followed
      by recrystallization of the product from N,N'-dimethylformamide (DMF) leads to
      trans-[Pd(L(n))(2)Cl(2)] x nDMF {L(3), n=0 (4), n=1(4( *)DMF); L(4)=2-chloro-6
      [(2,3-dimethoxybenzyl)-amino]-9-isopropylpurine, n=0 (5), n=1.5 (5( *)DMF). The
      compounds have been characterized by elemental analyses, conductivity
      measurements, electrospray mass spectra in the positive ion mode (ES+MS), FTIR,
      (1)H and (13)C NMR spectra, thermogravimetric analysis (TGA) and differential
      scanning calorimetry (DSC). Moreover, the complexes 2 and 6 have been also
      investigated by (15)N NMR spectroscopy. The molecular structures of L(5),
      {(H(2+)L(5))(Cl(-))(2)} x H(2)O, i.e. the protonated form of L(5), trans
      [Pd(L(3))(2)Cl(2)] (4) and trans-[Pd(L(4))(2)Cl(2)] (5) have been determined by
      single crystal X-ray analysis. NMR data and X-ray structures revealed that the
      organic molecules are coordinated to Pd via N7 atom of a purine moiety. All the
      complexes and the corresponding ligands have been tested in vitro for their
      cytotoxicity against four human cancer cell lines: breast adenocarcinoma (MCF7),
      malignant melanoma (G361), chronic myelogenous leukaemia (K562) and osteogenic
      sarcoma (HOS). Promising in vitro cytotoxic effect has been found for cis
      [Pd(L(2))(2)Cl(2)] (2), having the IC(50) values of 12, 10, 25, and 14 microM
      against MCF7, G361, K562, and HOS, respectively, and for trans
      [Pd(L(3))(2)Cl(2)].DMF (4) with the IC(50) value of 15 microM against G361.

PMID- 17208302
TI  - The C-terminus of complement factor H is essential for host cell protection.
AB  - Complement is a powerful self-amplifying system of innate immune defense with the
      capacity to eliminate microbes directly. Factor H is a central regulator in
      plasma which protects host tissue from complement mediated damage. Here we
      characterize the relevance of surface attached factor H, and study the regulatory
      activity of factor H on endothelial cells. Although these cells expressed
      membrane bound regulators, cell bound factor H contributed substantially to
      complement regulatory activity at the cell surface. Blockade of the C-terminus of
      factor H with monoclonal antibodies inhibited cell binding of this soluble
      regulator and resulted in enhanced complement activation on the cells. In the
      absence of factor H, increased deposition and slower inactivation of C3b resulted
      in higher amount of membrane attack complexes on the cell surface. When the
      membrane regulators CD55 and CD59 were removed by enzymatic treatment, complement
      mediated cell lysis was enhanced in the absence of factor H. Importantly,
      inhibition of the C-terminus did not compromise the regulatory function of factor
      H in fluid phase. Altogether these data point to a highly relevant, yet so far
      underestimated role of factor H for complement control at cellular surfaces, and
      reveal a decisive role of the factor H C-terminus in host cell recognition and
      protection.

PMID- 17208305
TI  - Cobalt complexes of terpyridine ligand: crystal structure and photocleavage of
      DNA.
AB  - Two new cobalt complexes, [Co(pytpy)(2)](ClO(4))(2), 1, and
      [Co(pytpy)(2)](ClO(4))(3), 2 where pytpy=pyridine terpyridine, have been
      synthesized and characterized. Single-crystal X-ray structure of both the
      complexes has been resolved. The structure shows the complexes to be a monomeric
      cobalt(II) and cobalt(III) species with two pytpy ligands coordinated to the
      metal ion to give a six coordinate complex. Both cobalt(II) and cobalt(III)
      complexes crystallize in meridional configuration. The interaction of these
      complexes with calf thymus DNA has been explored by using absorption, emission
      spectral, electrochemical studies and viscosity measurements. From the
      experimental results the DNA binding constants of 1 and 2 are found to be (1.97+/
      0.15)x10(4)M(-1) and (2.7+/-0.20)x10(4)M(-1) respectively. The ratio of DNA
      binding constants of 1 and 2 have been estimated to be 0.82 from electrochemical
      studies, which is in close agreement with the value of 0.73 obtained from
      spectral studies. The observed changes in viscosity of DNA in the presence of
      increasing amount of complexes 1 and 2 suggest intercalating binding of these
      complexes to DNA. Results of DNA cleaving experiments reveal that complex 2
      efficiently cleaves DNA under photolytic conditions while complex 1 does not
      cleave DNA under similar conditions.

PMID- 17208306
TI  - How can we best use structural information on P-glycoprotein to design
      inhibitors?
AB  - This year marks the 30th anniversary of the discovery of the multidrug resistance
      (MDR) ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp). Since then a
      considerable research effort has attempted to provide a greater understanding of
      the biological enigma of "multidrug" efflux. Moreover, the growing correlation
      between P-gp expression and a negative prognosis or poor outcome for chemotherapy
      has sparked significant interest in the generation of inhibitors. How close are
      we to overcoming the unwanted actions of P-gp in resistant cancer following 30
      years of research? The initial inhibitors were pre-existing clinically used
      compounds and exploited the broad specificity of P-gp. Unfortunately, the
      concentrations required to inhibit P-gp meant that these compounds generated
      considerable toxicity. Pharmacological investigations progressed to rational
      design using the 1st generation compounds as a template structure. Inherent
      toxicity of the drugs was reduced; however, pharmacokinetic interactions with the
      anticancer drugs were unsustainable. Generation of the most recent of inhibitors
      employed combinatorial chemistry to produce a handful of potent and selective P
      gp inhibitors. Some of these drugs have progressed to clinical trials with poor
      results or in some cases, undisclosed progress. There remains a clear need for
      the generation of P-gp inhibitors and this review describes the potential for a
      structure-based design to facilitate this undertaking. In particular, the
      plethora of functional data can provide important regions on the protein that
      could conceivably be exploited as inhibitor targets.

PMID- 17208307
TI  - A randomized comparison of dexamethasone 0.15 mg/kg versus 0.6 mg/kg for the
      treatment of moderate to severe croup.
AB  - BACKGROUND: Although previous studies have shown that dexamethasone is useful in
      croup, the optimal dosage has not been clarified yet. The aim of this study was
      to investigate the effectiveness of dexamethasone 0.15 mg/kg single dose compared
      with the recommended dose of 0.6 mg/kg for treatment of hospitalized children
      with moderate to severe croup. METHOD: Forty-one children aged 6 months to 5
      years admitted from March 2001 to October 2003 at the pediatric ward of Hatyai
      Hospital with moderate to severe croup were recruited for the study. After random
      allocation, each child received a single intravenous injection of either
      dexamethasone 0.6 mg/kg (maximum dose 12 mg) or 0.15 mg/kg (maximum dose 3 mg).
      All children were given a single dose of epinephrine nebulization at the
      beginning of the study. The croup scores were measured at 0, 1, 2, 3, 4, 6, 8, 10
      and 12 h after the dexamethasone injection. RESULTS: One hour following the
      injection, the mean croup scores were significantly reduced from baseline values
      in both groups (p<0.01). There was no difference in the mean croup scores between
      the two groups at any time. Median times to croup scores equal or less than two
      in both high- and low-dose groups were 8 and 7.9 h, respectively. No patient
      required intubation or was removed from the study because of a rising croup score
      after enrollment. There was no significant adverse reaction from dexamethasone
      treatment in either group. CONCLUSION: Dexamethasone 0.15 and 0.6 mg/kg are
      equally effective in the treatment of moderate to severe croup.

PMID- 17208308
TI  - Immunohistochemical expression of epidermal growth factor receptor and
      cyclooxygenase-2 in pediatric nasopharyngeal carcinomas: no significant
      correlations with clinicopathological variables and treatment outcomes.
AB  - Epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) were
      separately found associated with prognosis in adult patients with nasopharyngeal
      carcinoma (NPC). To date, their expression patterns and prognostic utility have
      never been specifically addressed in children and adolescents. Thirty consecutive
      NPC patients aged<or==20 years and treated by radiotherapy (RT) with (n=14) or
      without (n=16) systemic chemotherapy (CT) were accrued between 1988 and 2001 in a
      single institute. The clinical outcomes were correlated with clinicopathological
      features in 30 patients and with immunostains of EGFR and COX-2 in 20 patients
      with available blocks. The 5-year rates of overall survival (OS) and disease-free
      survival (DFS) were both 76.4%. Overexpression of EGFR and COX-2 was identified
      in 13 (65%) and 14 (70%) cases, respectively. The expression levels of these two
      oncoproteins did not significantly correlate with each other, DFS, OS, and any of
      clinicopathological factors, including histological subtype, AJCC stage, T stage,
      and N stage. The only significant prognosticator predictive of adverse outcomes
      was AJCC stage IV at presentation, which, compared with lower-staged diseases,
      decreased the rates from 85.2% to 55.6% at 5 years for both DFS (p=0.05) and OS
      (p=0.05). Despite lacking significant prognostic values, EGFR and COX-2 were
      overexpressed in approximately two-thirds of pediatric NPC. Such high frequencies
      provide the basis of combined targeted therapy by specific pharmacological
      inhibitors to enhance the effects of RT and CT. However, it requires further
      investigation on the difference between pediatric and adult NPC patients in
      clinical and biological implications of EGFR and COX-2.

PMID- 17208309
TI  - C-type natriuretic peptide: a new endothelium-derived hyperpolarizing factor?
AB  - Vascular relaxation mediated by endothelium-derived hyperpolarizing factor (EDHF)
      is important for resistance artery function and is underpinned by
      hyperpolarization of the smooth muscle cells of the blood vessel wall. Debate
      surrounds the identity of EDHF and its mechanism of action, with the consensus
      being that there is no universal EDHF. Regional differences in vascular function
      reflect the complex mechanisms of EDHF. Two primary mechanistic pathways are
      implicated: (i) myoendothelial gap junctions mediating the spread of endothelial
      cell hyperpolarization or small signaling molecules (or both) to the smooth
      muscle; and (ii) diffusible mediators released from the endothelium, including K+
      and epoxyeicosatrienoic acids. Here, we discuss the evidence for and against C
      type natriuretic peptide (CNP), the latest candidate for a diffusible mediator.

PMID- 17208310
TI  - Separation of near full-length hepatitis C virus quasispecies variants from a
      complex population.
AB  - A long RT-PCR (LRP) protocol was developed recently for robust amplification of a
      near full-length HCV genomic sequence from clinical samples, followed by
      efficient cloning [Fan, X., Xu, Y., Di Biceglie, A.M., 2006. Efficient
      amplification and cloning of near full-length hepatitis C virus genome from
      clinical samples. Biochem. Biophys. Res. Commun. 346, 1163-1172]. In the present
      study, the LRP protocol has been estimated for its error rate and the validation
      by sequencing fully the near full-length HCV inserts from six recombinant clones
      derived from a patient sample with complex viral diversity. These sequences were
      compared with the near full-length HCV sequence that was generated by direct
      sequencing of multiple overlapped PCR products from the same sample, referred to
      as the population sequence. Comparative analysis confirmed the artificial nature
      of the PCR-assembled population sequence and identified potential domains for
      linked viral mutations. The data also suggested that the hypervariable region 1
      (HVR1) may be a biological marker for the phenotype at the quasispecies level.
      These observations emphasize the significance of the use of near full-length
      genomic sequences for HCV genetic studies and for reverse genetic analysis using
      authentic quasispecies variants.

PMID- 17208311
TI  - Comparison of the RIDASCREEN norovirus enzyme immunoassay to IDEIA NLV GI/GII by
      testing stools also assayed by RT-PCR and electron microscopy.
AB  - RIDASCREEN norovirus enzyme immunoassay (EIA) detected 80.3% of norovirus
      infected feces samples compared to 60.6% by IDEIA NLV GI/GII from 228 patients
      with no false positives by either assay. RT-PCR and electron microscopy percent
      sensitivity and specificity were 98.5, 100 and 36.4 and 96.9, respectively.

PMID- 17208312
TI  - Production of sumoylated proteins using a baculovirus expression system.
AB  - Spodoptera frugiperda Sf9 cells were found to possess an active endogenous
      sumoylation system. However, the endogenous sumoylation machinery did not
      efficiently modify exogenous proteins expressed by infection with recombinant
      baculoviruses. To overcome this limitation, mammalian sumoylation components were
      introduced by co-infection with recombinant baculoviruses expressing individual
      protein components of the sumoylation pathway. Expression of mammalian Ubc9 plus
      SUMO (either SUMO1 or SUMO3) was necessary and sufficient for active sumoylation
      of co-infected test proteins. This system provides a simple and convenient means
      to produce sumoylated mammalian proteins in a eukaryotic environment. Large-scale
      cultures should provide quantities of sumoylated proteins sufficient for
      potential purification.

PMID- 17208313
TI  - Substance P injected into the dorsal periaqueductal gray causes anxiogenic
      effects similar to the long-term isolation as assessed by ultrasound
      vocalizations measurements.
AB  - Housing conditions change the emotional state of the animals. Ultrasound
      vocalizations (USVs) termed as 22 kHz are the usual components of the defensive
      responses of rats exposed to threatening conditions such as isolation. The amount
      of emission of 22 kHz USVs depends on the intensity of the aversive stimuli.
      While short periods of isolation caused an anxiolytic-sensitive enhancement of
      the defensive responses, long-term isolation tended to reduce the defensive
      performance of the animals to aversive stimuli. The dorsal periaqueductal gray
      (dPAG) is an important vocal center and a crucial structure for the expression of
      defensive response. While it has been shown that Substance P (SP) at this
      midbrain level is involved in the modulation of the defensive response, its role
      in the emission of ultrasound vocalizations has not been evaluated. In this study
      we examined whether the resocialization and local injections of SP into the dPAG
      have an influence on the isolation-induced 22 kHz USVs recorded within the
      frequency range of 18-26 kHz. Rats isolated for 1 day showed a significant
      increase in the number and duration of USVs, which were reversed by
      resocialization. On the other hand, 2-week isolation reduced the number and
      duration of 22 kHz USVs, which could not be reversed by resocialization. SP
      injections into the dPAG (35 pmol/0.2 microL) caused a reduction in the 22 kHz
      USVs. Pretreatment with the NK-1 receptor antagonist spantide (100 pmol/0.2
      microL) blocked these effects but exhibited no effect when given alone. These
      findings suggest that 1-day and 2-week isolation recruit distinct brain defensive
      systems. Also, in agreement with the notion that intense fear is associated with
      the neural substrates of fear of the dPAG, activation of NK-1 receptors of this
      midbrain structure reduces the 22 kHz USVs.

PMID- 17208314
TI  - Resistance mutations at the lipid substrate binding site of Plasmodium falciparum
      protein farnesyltransferase.
AB  - The post-translational farnesylation of proteins serves to anchor a subset of
      intracellular proteins to membranes in eukaryotic organisms and also promotes
      protein-protein interactions. This enzymatic reaction is carried out by protein
      farnesyltransferase (PFT), which catalyzes the transfer of a 15-carbon isoprenoid
      lipid unit, a farnesyl group, from farnesyl pyrophosphate to the C-termini of
      proteins containing a CaaX motif. Inhibition of PFT is lethal to the pathogenic
      protozoa Plasmodium falciparum. Previously, we have shown that parasites
      resistant to a tetrahydroquinoline (THQ)-based PFT inhibitor BMS-388891 have
      mutations leading to amino acid substitutions in PFT that map to the peptide
      substrate binding domain. We now report the selection of parasites resistant to
      another THQ PFT inhibitor BMS-339941. In whole cell assays sensitivity to BMS
      339941 was reduced by 33-fold in a resistant clone, and biochemical analysis
      demonstrated a corresponding 33-fold increase in the BMS-339941 K(i) for the
      mutant PFT enzyme. More detailed kinetic analysis revealed that the mutant enzyme
      required higher concentration of peptide and farnesyl pyrophosphate substrates
      for optimum catalysis. Unlike previously characterized parasites resistant to BMS
      388891, the resistant parasites have a mutation which is predicted to be in a
      distinct location of the enzymatic pocket, near the farnesyl pyrophosphate
      binding pocket. This is the first description of a mutation from any species
      affecting the farnesyl pyrophosphate binding pocket with reduced efficacy of PFT
      inhibitors. These data provide further support that PFT is the target of THQ
      inhibitors in P. falciparum and suggest that PFT inhibitors should be combined
      with other antimalarial agents to minimize the development of resistant
      parasites.

PMID- 17208315
TI  - Signaling pathways implicated in oncostatin M-induced aggrecanase-1 and matrix
      metalloproteinase-13 expression in human articular chondrocytes.
AB  - Molecular mechanisms of oncostatin M (OSM)-stimulated cartilage extracellular
      matrix catabolism and signaling pathways were investigated in human arthritic
      chondrocytes. OSM, alone or with Interleukin-1 (IL-1beta), increased
      glycosaminoglycan release and induced ADAMTS-4 and MMP-13 protein expression in
      human cartilage explants. OSM dose- and time-dependently increased ADAMTS-4 mRNA
      and MMP-13 protein expression in human femoral head chondrocytes. Extracellular
      signal-regulated kinases (ERK1/2)-MAPK pathway inhibitor, U0126, down-regulated
      ADAMTS-4 and MMP-13 induction by OSM. Janus kinase 2 (JAK2) inhibitor, AG490,
      suppressed OSM-induced ADAMTS-4 mRNA expression but did not affect MMP-13 levels
      while JAK3 pharmacological inhibitor and siRNA transfection suppressed both.
      Parthenolide, a signal transducer and activator of transcription (STAT1 and
      STAT3) phosphorylation inhibitor, reduced OSM-induced ADAMTS-4 and MMP-13 gene
      expression and prevented STAT1/3 DNA binding activity. Additionally, OSM-enhanced
      ADAMTS-4 mRNA and MMP-13 expression was down-regulated by phosphatidylinositol 3
      kinase (PI3K) and Akt/PKB inhibitors, LY294002 and NL-71-101. Furthermore, JAK3
      inhibition time-dependently down-regulated Akt but not ERK1/2 phosphorylation
      suggesting that Akt is a downstream target of JAK3. These results suggest that
      OSM-stimulated ADAMTS-4 and MMP-13 expression is mediated by ERK1/2, JAK3/STAT1/3
      and PI3K/Akt and by cross talk between these pathways. The inhibitors of these
      cascades could block OSM-evoked degeneration of cartilage by ADAMTS-4 and MMP-13.

PMID- 17208316
TI  - Regulation of MAP kinases by MAP kinase phosphatases.
AB  - MAP kinase phosphatases (MKPs) catalyze dephosphorylation of activated MAP kinase
      (MAPK) molecules and deactivate them. Therefore, MKPs play an important role in
      determining the magnitude and duration of MAPK activities. MKPs constitute a
      structurally distinct family of dual-specificity phosphatases. The MKP family
      members share the sequence homology and the preference for MAPK molecules, but
      they are different in substrate specificity among MAPK molecules, tissue
      distribution, subcellular localization and inducibility by extracellular stimuli.
      Our understanding of their protein structure, substrate recognition mechanisms,
      and regulatory mechanisms of the enzymatic activity has greatly increased over
      the past few years. Furthermore, although there are a number of MKPs, that have
      similar substrate specificities, non-redundant roles of MKPs have begun to be
      identified. Here we focus on recent findings regarding regulation and function of
      the MKP family members as physiological regulators of MAPK signaling.

PMID- 17208317
TI  - Membrane lipid rafts coordinate estrogen-dependent signaling in human platelets.
AB  - The impact of estrogens on the viability of cardiovascular system and their
      ability to regulate platelet function is still an open and debated question. We
      have previously shown that estrogen is able to significantly potentiate the
      aggregation induced by low doses of thrombin and to initiate a rapid and
      reversible signaling pathway mediated by ERbeta-directed activation of the
      tyrosine kinases Src and Pyk2 at the level of the plasma membrane. Lipid rafts
      are critical, cholesterol-enriched membrane domains, which play a major role in
      blood platelet activation processes. In this work, we investigated the role of
      lipid rafts in 17beta-estradiol signaling in human platelets. We observed that
      membrane rafts were essential for both 17beta-estradiol-dependent potentiation of
      platelet aggregation induced by subthreshold concentrations of thrombin and
      17beta-estradiol-induced phosphorylation of Src. 17beta-estradiol caused the
      reversible translocation of ERbeta to the raft fractions and promoted the rapid
      and transient recruitment to, and activation within the membrane raft domains of
      the tyrosine kinases Src and Pyk2. The raft integrity was essential with this
      respect, as these effects of 17beta-estradiol were completely inhibited by
      cholesterol depletion. This paper provides evidence for the first time that
      membrane lipid rafts coordinate estrogen signaling in human platelets.

PMID- 17208318
TI  - Serotonin 5-HT1A receptor stimulates c-Jun N-terminal kinase and induces
      apoptosis in Chinese hamster ovary fibroblasts.
AB  - The 5-HT1A receptor is a prototypical member of the large and diverse serotonin
      receptor family. One key role of this receptor is to stimulate cell proliferation
      and differentiation via the extracellular signal regulated protein kinase (ERK)
      mitogen activated protein (MAP) kinase. There are few reports on the ability of
      the 5-HT1A receptor to modulate other MAP kinases such as c-Jun N-terminal kinase
      (JNK), which is activated by various extracellular stimuli, resulting in cell
      growth, differentiation, and programmed cell death. We report here for the first
      time that the 5-HT1A receptor stimulates JNK. JNK stimulation was Pertussis toxin
      sensitive and was mediated by Rho family low molecular weight GTPases. The 5-HT1A
      receptor also increased apoptosis, which was mimicked by the MEK inhibitor
      PD98059, and blocked by the JNK inhibitor SP600125. These results suggest that
      the 5-HT1A receptor stimulates both ERK-dependent anti-apoptotic pathways and JNK
      dependent pro-apoptotic pathways in CHO cells.

PMID- 17208319
TI  - Sudden death prophylaxis in heart failure.
AB  - Sudden cardiac death (SCD) is the leading cause of mortality in heart failure
      (HF). Today the implantable cardioverter-defibrillator (ICD) has become a
      commonplace therapy around the world for patients with both ischemic and non
      ischemic cardiomyopathy and an ejection fraction (EF) < or = 35%. However, EF
      alone does not discriminate between the modes of death from HF (sudden arrhythmic
      death vs. non-sudden death). Other risk statifiers, such as electrophysiologic
      study and microvolt T-wave alternans testing, should therefore be used in the
      appropriate settings to minimize the number of unnecessary device implants. In
      addition, left ventricular mechanical dyssynchrony has now become recognized as
      an additional major marker of cardiac mortality. Its assessment should entail
      echocardiography rather than measurement of the QRS duration. This will allow us
      to better integrate the ability of cardiac resynchronization therapy (CRT) in
      enhancing cardiac function with the ability of an ICD in preventing SCD. This
      review aims to: 1) give a synthesis of the published evidence regarding the value
      of implantable ICDs and CRT in the primary prophylaxis of SCD in HF; 2) discuss
      controversial clinical issues in this area; and 3) recommend practical device
      based management strategies.

PMID- 17208321
TI  - Bacterial flora and risk of infection of the ovine teat duct and mammary gland
      throughout lactation.
AB  - We collected samples of teat duct material and mammary secretion from ewes in
      three farms (flock A, polyparous n=7; flock B, polyparous n=6, primiparous n=4;
      flock C, polyparous n=4): 14 samples immediately after lambing (before sucking of
      lambs), 244 samples during the suckling period and 156 samples during the milking
      period. Conventional bacteriological techniques were used. The results were
      modeled using survival analysis, initially by the Kaplan-Meier method and then by
      the Cox Proportional Hazards method. Then, we calculated the minimum true risk of
      an "at-risk" teat or mammary gland being infected and analyzed these data with
      STATA using the GLLAMM program for Generalised Linear Latent and Mixed Models.
      During the suckling period, bacteria were isolated from 52 (21%) duct material
      and 19 (8%) secretion samples; respective results for the milking period were 20
      (13%) and 9 (6%). There was an increased risk of duct rather than secretion
      samples being infected (P<0.001). There was a significant difference among flocks
      in isolating bacteria from duct (P<0.01) or secretion (P<0.001) samples during
      suckling period, but not during hand-milking period (P>0.4 and 0.1,
      respectively). There were no differences between isolation of bacteria from duct
      (P>0.5) or secretion (P>0.7) samples among primiparous and polyparous animals.
      Most bacterial isolates were staphylococci. Persistent isolation of the same
      bacterial species from duct material samples obtained from a particular ewe was
      recorded with five Staphylococcus spp. and two Mannheimia haemolytica isolates.
      The results indicate that infections of the teat duct can take place easily;
      however, not all infections result to infection of the mammary gland. The results
      support experimental evidence that defence mechanisms of the healthy teat are
      able to limit the infection. Maintenance of healthy teats contributes to
      effective defence mechanisms, and coupled with minimal infections of the teat
      duct, would contribute to the prevention of mastitis in ewes.

PMID- 17208320
TI  - Peripartum cardiomyopathy: a comprehensive review.
AB  - Peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular
      dysfunction and symptoms of heart failure occur in the peripartum period in
      previously healthy women. Incidence of PPCM ranges from 1 in 1300 to 1 in 15,000
      pregnancies. The etiology of PPCM is unknown, but viral, autoimmune, and
      idiopathic causes may contribute. The diagnostic criteria are onset of heart
      failure in the last month of pregnancy or in first 5 months postpartum, absence
      of determinable cause for cardiac failure, and absence of a demonstrable heart
      disease before the last month of pregnancy. Risk factors for PPCM include
      advanced maternal age, multiparity, African race, twinning, gestational
      hypertension, and long-term tocolysis. The clinical presentation of patients with
      PPCM is similar to that of patients with dilated cardiomyopathy. Early diagnosis
      and initiation of treatment are essential to optimize pregnancy outcome.
      Treatment is similar to medical therapy for other forms of dilated
      cardiomyopathy. About half the patients of PPCM recover without complications.
      The prognosis is poor in patients with persistent cardiomyopathy. Persistence of
      disease after 6 months indicates irreversible cardiomyopathy and portends worse
      survival.

PMID- 17208322
TI  - Indirect detection of Bacillus anthracis using real-time PCR to detect amplified
      gamma phage DNA.
AB  - Typical real-time PCR methods used to identify Bacillus anthracis do not
      distinguish between viable and non-viable spores, which would be critical in any
      first response and remediation scenarios. This study combined both real-time PCR,
      using primers specifically designed for gamma phage, with the highly specific
      gamma phage amplification into one simple assay to indirectly detect Bacillus
      anthracis. Since the amplification of gamma phage only occurs in the presence of
      a suitable host, the detection of increasing concentrations of progeny gamma
      phage DNA using real-time PCR implies the presence of viable Bacillus anthracis
      cells. This method detected a starting Bacillus anthracis concentration of 207
      cfu/mL, equivalent to less than one cell in 20 microL, in less than 5 h.

PMID- 17208323
TI  - MLST-v, multilocus sequence typing based on virulence genes, for molecular typing
      of Salmonella enterica subsp. enterica serovars.
AB  - Salmonella enterica subsp. enterica is one of the main causative agents of food
      borne disease in man, and can also be the cause of serious systemic illness.
      Organisms belonging to this genus have traditionally been classified on the basis
      of the antigenic properties of the cell-surface lipopolysaccharide and of the
      phase 1 and phase 2 flagellar proteins. Primary isolation, biochemical
      identification, and serotyping are laborious and time consuming. Molecular
      identification based on suitable marker genes could be an attractive alternative
      to conventional bacteriological and serological methods. We have assessed the
      applicability of two housekeeping genes, gyrB, atpD, in combination with the
      flagellin genes fliC and fljB in multilocus sequence typing of Salmonella.
      Sequencing and comparative analysis of sequence data was performed on multiple
      strains from Austria, the United Kingdom, and Switzerland, representing all
      subspecies and 22 of the more prevalent non-typhoid S. enterica subsp. enterica
      serovars. A combination of these four marker genes allowed for a clear
      differentiation of all the strains analysed, indicating their applicability in
      molecular typing. The term MLST-v, for multilocus sequence typing based on
      virulence genes, is proposed to distinguish this approach from MLST based solely
      on housekeeping genes. An assortative recombination of the fliC gene was found in
      seven of the analysed serovars indicating multiple phylogenetic origin of these
      serovars.

PMID- 17208324
TI  - Small molecules: the lexicon of biodiversity.
AB  - The extent of microbial diversity in the Biosphere is not known (and probably
      never will be!). One aspect of this diversity is the production of biologically
      active small molecules; within the Streptomycetes alone this may be millions of
      compounds with an extraordinary diversity and complexity of structure. First
      recognised as pigments and later, in the 1950s, as antibiotics, it is now clear
      that the small molecules produced by microbes have many different functions in
      nature. This huge collection of biologically active compounds with various
      properties has been used as pharmaceuticals and agriculturals. They also interact
      with proteins and RNA with high specificity and have been shown to be regulators
      and effectors of diverse biochemical reactions. The use of small molecules (other
      than as pharmaceuticals) deserves to be explored in order to exploit microbial
      biotechnology to the full.

PMID- 17208325
TI  - Development of a glycine-inducible expression system for Bacillus subtilis.
AB  - Riboswitches are binding domains for metabolites located within the 5'
      untranslated regions (UTR) of mRNA molecules. With two exceptions, binding of the
      metabolite prevents expression of the downstream gene(s). In one of these
      exceptions, binding of the metabolite glycine triggers expression of the
      downstream genes in Bacillus subtilis involved in degradation of this amino acid
      if present at high amounts. First, we confirmed by Northern blot the presence of
      a small transcript corresponding to the 5' UTR in the absence of glycine which is
      converted into the full-length transcript after addition of the amino acid.
      Surprisingly, the truncated transcript continued to be synthesized. We could show
      that neither increased stability is responsible for the continued presence of
      this truncated transcript nor does it result from processing of the full-length
      transcript. Next, we fused the promoter and the downstream riboswitch to the lacZ
      reporter gene and demonstrated glycine-dependent induction. Furthermore, we
      increased the promoter strength to obtain higher levels of recombinant proteins
      as shown by using HtpG and alpha-amylase as model proteins. This is the first
      report that a naturally occurring riboswitch can be used for controllable
      overproduction of recombinant proteins using the inexpensive inducer glycine.

PMID- 17208326
TI  - Metabolic improvement of male prisoners with type 2 diabetes in Fukushima Prison,
      Japan.
AB  - Imprisonment often improves metabolic control in prisoners with type 2 diabetes;
      however, the reasons for this remain unclear. Here, we investigated the metabolic
      control of male prisoners with type 2 diabetes in Japan. Retrospective analysis
      of 4385 medical charts of male prisoners in Fukushima Prison from 1998 to 2004
      revealed 109 prisoners (all Asian) with type 2 diabetes (mean+/-S.D.: 51+/-10
      years). All were followed up during their imprisonment (14+/-10 months). During
      imprisonment, mean fasting plasma glucose and hemoglobin Alc (HbA1c) levels
      dramatically decreased from 184+/-74 to 113+/-38mg/dl (p<0.001) and 8.4+/-2.1 to
      5.9+/-1.2% (p<0.001), respectively. In addition, 5 of 18 prisoners (28%) treated
      with insulin and 17 of 34 (50%) treated with oral hypoglycemic agents were able
      to discontinue their treatment and maintain good metabolic control. Most
      prisoners in Japanese prisons work 8h a day 5 days a week, consuming a high
      dietary fiber diet including boiled rice with barley, "Mugimeshi". These findings
      suggest that a well-regulated lifestyle and long-term intake of high dietary
      fiber may have beneficial effects on metabolic control in patients with type 2
      diabetes.

PMID- 17208327
TI  - The road to crossovers: plants have their say.
AB  - Crossovers involve the reciprocal exchange of large fragments of genetic material
      between homologous chromosomes during meiosis. In this way, crossovers are the
      basis of genetics. Remarkably, the number and distribution of crossovers on
      chromosomes are closely controlled. Data from various model organisms (notably
      Saccharomyces cerevisiae) show that the distribution of crossovers results from a
      series of tightly regulated events involving the formation and repair of double
      strand breaks and interference. Recent advances in genetic and cytological tools,
      particularly for studying Arabidopsis thaliana, have enabled crossover control in
      plants to be studied in more detail. In this article, we discuss the contribution
      of plant studies to meiosis research, particularly to our understanding of
      crossover control and interference, and we evaluate models of interference.

PMID- 17208328
TI  - Influence of MMP-2 and MMP-9 promoter polymorphisms on gene expression and
      clinical outcome of non-small cell lung cancer.
AB  - Matrix metalloproteinases (MMP) including MMP-2 and MMP-9 play a major role in
      tumour invasion by proteolysing the extracellular matrix. Their activation,
      particularly that of MMP-9, is partly dependent on plasmin that is inhibited by
      TFPI-2 (tissue factor pathway inhibitor-2), a serine protease inhibitor whose
      gene expression is decreased in about one-third of non-small cell lung cancers
      (NSCLC). In addition, MMP-2 and MMP-9 are essential in the development of NSCLC
      and can be regulated by functional promoter polymorphisms. In this study, the 
      1306C/T MMP-2, -735C/T MMP-2 and -1562C/T MMP-9 polymorphisms were analysed in 90
      NSCLC patients and 90 controls. In addition, the promoter region of the TFPI-2
      gene was screened for sequence variations in both groups by DHPLC. A -167G/A
      polymorphism was identified in 3% of controls whereas none of the 90 patients
      exhibited this genetic variation in the TFPI-2 promoter region. Moreover, no
      difference in -1306C/T MMP-2, -735C/T MMP-2 and -1562C/T MMP-9 genotypes was
      found between cases and controls. However, the homozygous -1562CC MMP-9 genotype
      was more frequent in patients with squamous cell carcinoma than in controls
      (p=0.018). When genotype distributions were compared to MMP-2 and MMP-9 gene
      expression in tumours, no relationship was found with the -1306 MMP-2 and -1562
      MMP-9 polymorphisms. In contrast, tumour MMP-2 gene expression was lower in
      homozygous -735CC patients than in those with CT or TT genotypes. In addition,
      the survival time was longer in patients with the MMP-2 -735T allele than in
      those with the CC genotype (p=0.02). The relative risk of death was increased 2.6
      fold in -735CC patients (p=0.045; 95% CI=1.0-6.7). The results of this study
      suggest that the -735C/T MMP-2 polymorphism might be an independent prognostic
      marker in NSCLC, but this should be confirmed in a larger cohort of patients.

PMID- 17208329
TI  - Mediastinal signet-ring cell carcinoma of unknown primary: long-term survival by
      treatment with S-1, a novel derivative of 5-fluorouracil.

PMID- 17208330
TI  - A phase II study of oral vinorelbine in combination with cisplatin conducted in
      Taiwan in patients with unresectable localized or metastatic non-small cell lung
      carcinoma.
AB  - BACKGROUND: Intravenous vinorelbine plus cisplatin is widely prescribed for the
      treatment of NSCLC. The objective of this phase II study was to define the
      efficacy of an oral form of vinorelbine combined with cisplatin for first line
      treatment of advanced/metastatic NSCLC. PATIENTS AND METHODS: From September 2002
      to December 2003, 46 chemotherapy-naive patients received 80 mg/m(2) of cisplatin
      on day 1 and oral vinorelbine at 60 mg/m(2) on days 1 and 8, every 3 weeks.
      RESULTS: After an independent panel review, the response rate was 37.5 % [95%
      confidence interval (CI): 22.7-54.2%] in the evaluable population and 32.6% [95%
      CI: 19.5-48] in the intent-to-treat population. Median progression-free survival
      was 5.6 months and overall survival was 11.2 months. Grades 3 and 4 neutropenia
      was observed in 58.7% of patients, with febrile neutropenia and neutropenic
      infection in 4.3 and 8.7% of patients, respectively. The main non-haematological
      toxicities were hypotension, fatigue (8.7% for each) and gastrointestinal
      disorders with rare grades 3 and 4. CONCLUSIONS: These results suggest that the
      combination of cisplatin at 80 mg/m(2) on day 1 with oral vinorelbine at 60
      mg/m(2) on days 1 and 8, every 3 weeks, is an active regimen, associated with
      acceptable toxicity. Oral vinorelbine is therefore a good alternative to the i.v.
      formulation.

PMID- 17208331
TI  - Differential expression profile of MAGE family in non-small-cell lung cancer.
AB  - The expression of the melanoma-associated antigen (MAGE) genes consists of
      variables in all tumor types, such as lung cancer, which are relevant to be
      silent in all normal tissues except germ cells. They are considered as tumor
      specific antigens, and are ideal targets for cancer immunotherapy. A complete
      MAGE genes differential expression profile analysis of lung cancer can provide
      this study not only various target genes for immunotherapy, but also valuable
      markers for further diagnosis and prognosis. This research has constructed a
      membrane array, which was consisted 32 MAGE genes, to detect whether the
      differential expression profile occurred in 52 pairs of non-small-cell lung
      cancer (NSCLC) samples. Nearly 32 MAGE genes have been differential expressed in
      NSCLC except MAGE-B1 and -E2. MAGE-B, -C, -D, and subgroup -B6, -D4 have showed
      prominences in lung adenocarcinoma. High-frequent expression of MAGE-D, and
      subgroup -A2, -D2 has also been discovered in non-metastasis group (p<0.05).
      However, there is no significant difference of MAGE genes differential expression
      shown among different primary tumor (T), nodal involvement (N) and overall
      stages. Several MAGE subgroup genes, such as MAGE-A5, -A7, -A8, -A9, -A11, -B3, 
      B4, -B10, -D2, -D3, -F1, -G1, -H1, and -L2, have been first discovered to show
      differential expression in NSCLC. Although the small size of the sample may limit
      the diagnostic and prognostic value of MAGE genes, the function of the membrane
      array can provide this study a high-throughput method to detect the whole MAGE
      genes differential expression profile.

PMID- 17208332
TI  - An increased lung cancer risk associated with codon 72 polymorphism in the TP53
      gene and human papillomavirus infection in Mazandaran province, Iran.
AB  - The TP53 gene has a polymorphism in exon 4 at codon 72 that presents the arginine
      or proline genotype. The association of TP53 codon 72 polymorphism with lung
      cancer risk has been studied by several groups, although with inconsistent
      results. Our previous study showed that the human papillomavirus (HPV) infection
      is associated with the development of lung cancer in Mazandaran, north part of
      Iran (cases=25.6% versus controls=9.0%, P=0.002). The frequency of TP53 codon 72
      polymorphism was studied in a north part Iranian group of 92 healthy controls and
      141 lung cancer patients. The allelic distribution of the three genotypes
      (ArgArg, ArgPro, ProPro) in healthy normal controls was 46.1, 32.6 and 21.3%,
      respectively, which differs from that of lung cancer patients showing genotype
      frequency as 42.6, 49.6 and 7.8%. A relation between the presence of the Arg
      allele and lung cancer risk was observed. Our study reveals that Arg allele,
      active smoking and HPV infection are the important risk factors in lung cancer
      development in the north part of Iran, Mazandaran province.

PMID- 17208333
TI  - Modulation of beta-catenin by cyclin-dependent kinase 6 in Wnt-stimulated cells.
AB  - Beta-catenin is implicated in quite different cellular processes, which require a
      fine-tuned regulation of its function. Here we demonstrate that cyclin-dependent
      kinase 6 (CDK6), in association with cyclin D1 (CCND1), directly binds to beta
      catenin. We showed that CCND1-CDK6 phosphorylates beta-catenin on serine 45
      (S45). This phosphorylation creates a priming site for glycogen synthase kinase
      3beta (GSK3beta) and is both necessary and sufficient to initiate the beta
      catenin phosphorylation-degradation cascade. Moreover, co-immunoprecipitation
      assays using Wnt3a-conditioned medium reveals that while Wnt stimulation leads to
      the dissociation of beta-catenin from axin and casein kinase Ialpha (CKIalpha),
      Wnt treatment promotes an increase in CCND1 level and the association of beta
      catenin with CCND1-CDK6. Furthermore, Wnt3a-stimulated cytosolic beta-catenin
      levels were higher in CDK6 knockout mouse embryonic fibroblasts (CDK6-/- MEFs)
      compared to wild-type MEFs. Thus, the CCND1-CDK6 complex is like to negatively
      regulate Wnt signaling by mediating beta-catenin phosphorylation and its
      subsequent degradation in Wnt-stimulated cells.

PMID- 17208334
TI  - Two randomized studies demonstrate the efficacy and safety of dapsone gel, 5% for
      the treatment of acne vulgaris.
AB  - BACKGROUND: A new aqueous gel formulation of dapsone has been developed that
      allows clinically-effective doses of dapsone to be administered topically with
      minimal systemic absorption. OBJECTIVES: The goal of these studies was to
      evaluate the efficacy and safety of dapsone gel, 5% in the treatment of acne.
      METHODS: Patients 12 years of age and older with acne vulgaris (N = 3010)
      participated in two identically-designed 12-week, randomized, double-blind
      studies of twice-daily monotherapy with dapsone gel, 5%, versus a vehicle gel.
      RESULTS: Dapsone gel-treated patients achieved superior results in terms of the
      investigator's global acne assessment (P < .001) and the mean percentage
      reduction in inflammatory, noninflammatory, and total lesion counts (all, P <
      .001) at week 12. Reductions in inflammatory lesion counts favoring dapsone gel
      over vehicle were apparent as early as 2 weeks and reached statistical
      significance by 4 weeks. No clinically significant changes in laboratory
      parameters, including hemoglobin, even among glucose-6-phosphate dehydrogenase
      deficient patients, were observed. Adverse events were comparable between the
      treatment groups and rarely led to discontinuation. LIMITATIONS: Adjunctive
      topical treatments and their impact on acne were not studied in this trial.
      CONCLUSIONS: Dapsone gel, 5% appears to be an effective, safe, and well-tolerated
      treatment for acne vulgaris, with a rapid onset of action.

PMID- 17208335
TI  - Increased brain neuropeptide Y1 and Y2 receptor binding in NPY knock out mice
      does not result in increased receptor function.
AB  - The brain neuropeptide Neuropeptide Y (NPY) is an important modulator of a number
      of centrally mediated processes including feeding, anxiety-like behaviors, blood
      pressure and others. NPY produces its effects through at least four functional G
      protein coupled receptors termed Y1, Y2, Y4 and Y5. In the brain, the Y1 and Y2
      receptor subtypes are the predominant receptor population. To better understand
      the roles of NPY, genetically modified mice lacking NPY were produced but lacked
      the expected phenotypes. These mice have previously been reported to have a
      marked increase in Y2 receptor binding. In the present study, we found an
      upregulation of both Y1 and Y2 receptor binding and extended these findings to
      the female. These increases were as large as 10-fold or greater in many brain
      regions. To assess functional coupling of the receptors, we performed agonist
      induced [(35)S]GTPgammaS autoradiography. In the mouse brain, the Y1/Y4/Y5
      agonist Leu(31),Pro(34)-NPY increased [(35)S]GTPgammaS binding with a regional
      distribution consistent with that produced when labeling adjacent sections with
      [(125)I]-Leu(31),Pro(34)-PYY. In a few brain regions, minor increases were noted
      in the agonist-induced binding when comparing knock out mice to wild type. The Y2
      agonist C2-NPY stimulated [(35)S]GTPgammaS binding in numerous brain areas with a
      regional distribution similar to the binding observed with [(125)I]-PYY3-36.
      Again, no major increases were noted in the functional activation of Y2 receptors
      between knock out and wild type mice. Therefore, the increased Y1 and Y2 binding
      observed in the NPY knock out mice does not represent an increase in NPY receptor
      mediated signaling and is likely due to an increase in spare (uncoupled)
      receptors.

PMID- 17208337
TI  - WITHDRAWN: Combination of plant sterols and diacylglycerol oil lowers serum
      cholesterol and lipoprotein (a) concentrations in postmenopausal women with mild
      to-moderate hypercholesterolemia.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17208336
TI  - CSF and MRI markers independently contribute to the diagnosis of Alzheimer's
      disease.
AB  - BACKGROUND: Decreased amyloid beta (1-42) (Abeta42) and increased
      (phosphorylated) tau in cerebrospinal fluid (CSF) are considered to be a
      reflection of plaques, tangles, and neuronal degeneration in Alzheimer's disease
      (AD). Atrophy of the medial temporal lobe (MTA) on magnetic resonance imaging
      (MRI) reflects neuronal loss in this area. OBJECTIVE: To compare diagnostic
      accuracy of CSF biomarkers and MTA in AD versus controls. METHODS: Abeta42, tau
      and tau phosphorylated at threonine 181 (Ptau-181) were measured in CSF from 61
      AD patients and 32 controls by sandwich enzyme-linked immunosorbent assay. A CSF
      biomarker profile for AD was constructed. MTA was rated visually on MRI. RESULTS:
      When AD patients and controls were evaluated separately, no correlations were
      present between the CSF markers and MTA score. Both MTA and CSF biomarker profile
      were independently associated with the diagnosis AD (MTA: OR (95% CI)=28 (3-239);
      CSF biomarker profile: OR (95% CI)=57 (13-262)). Among individuals younger than
      65 years old and without MTA 60% suffered AD, and the finding of an abnormal CSF
      biomarker profile was limited to AD patients only. CONCLUSIONS: MTA and CSF
      biomarkers seem to be of incremental value for the diagnosis AD. CSF analysis is
      most sensitive in the absence of MTA, and especially among early-onset AD
      patients.

PMID- 17208338
TI  - Commensal bacteria do translocate across the intestinal barrier in surgical
      patients.
AB  - BACKGROUND: The "gut origin of sepsis" hypothesis proposes that enteric bacteria
      may cause sepsis at distant extra-intestinal sites. Whilst there is much
      circumstantial evidence to support this hypothesis, there is no conclusive proof
      in humans. The nature of translocating bacteria remains unclear. The aim of this
      study was to establish the origin of Escherichia coli (E. coli) cultured from
      mesenteric lymph nodes (MLN) and determine if they belonged to any recognized
      pathotypes known to cause infections in humans. METHODS: MLN and faecal samples
      were obtained from 98 patients undergoing colonic resection. E. coli were
      isolated from 9/98 MLN samples. DNA fingerprints of MLN isolates were compared
      with faecal isolates from the same patient. MLN isolates were tested for
      adherence and invasion using HEp-2 epithelial cells, and screened for DNA markers
      indicative of different pathotypes of E. coli. MLN isolates were also tested for
      internalisation into Caco-2 cells. RESULTS: All the nine E. coli cultured from
      MLNs were found to have identical DNA fingerprints to at least one and often
      several E. coli isolates cultured from faecal samples of the same patient. 8/9
      (89%) MLN isolates were weakly adherent and 2/9 (22.2%) were invasive. 8/9 (89%)
      tested negative for DNA markers. All the nine MLN strains were internalised by
      Caco-2 cells. CONCLUSION: This study confirms the gut origin of translocating
      bacteria. Most translocating E. coli do not belong to any recognised pathotype
      and are therefore normal commensal microflora. Our results suggest that bacterial
      translocation is more dependent upon the gut epithelium rather than the virulence
      properties of resident enteric bacteria.

PMID- 17208339
TI  - Convincing or confusing? Economic evaluations of childhood pneumococcal conjugate
      vaccination--a review (2002-2006).
AB  - We review 15 economic analyses of pneumococcal conjugate vaccines, published
      between 2002 and 2006, in terms of methodology, assumptions, results and
      conclusions. We found a great diversity in assumptions (eg, vaccine efficacy
      parameters, incidence rates for both invasive and non-invasive disease) mainly
      due to local variation in data and opinions. Accordingly, the results varied
      greatly, from total net savings to over euro 100,000 per discounted QALY gained.
      The cost of the vaccination program (determined by price per dose and schedule (4
      or 3 doses, or fewer)), and likely herd immunity impacts are highly influential
      though rarely explored in these published studies. If the net long-term impact
      (determined by a mixture of effects related to herd immunity, serotype
      replacement, antibiotic resistance and cross reactivity) remains beneficial and
      if a 3-dose schedule confers near-equivalent protection to a 4-dose schedule, the
      cost-effectiveness of PCV7 vaccination programs can be viewed as attractive in
      developed countries.

PMID- 17208341
TI  - Thrombin generation and fibrin clot structure.
AB  - Generation of a hemostatic clot requires thrombin-mediated conversion of
      fibrinogen to fibrin. Previous in vitro studies have demonstrated that the
      thrombin concentration present at the time of gelation profoundly influences
      fibrin clot structure. Clots formed in the presence of low thrombin
      concentrations are composed of thick fibrin fibers and are highly susceptible to
      fibrinolysis; while, clots formed in the presence of high thrombin concentrations
      are composed of thin fibers and are relatively resistant to fibrinolysis. While
      most studies of clot formation have been performed by adding a fixed amount of
      purified thrombin to fibrinogen, clot formation in vivo occurs in a context of
      continuous, dynamic changes in thrombin concentration. These changes depend on
      the local concentrations of pro- and anti-coagulants and cellular activities.
      Recent studies suggest that patterns of abnormal thrombin generation produce
      clots with altered fibrin structure and that these changes are associated with an
      increased risk of bleeding or thrombosis. Furthermore, it is likely that clot
      structure also contributes to cellular events during wound healing. These
      findings suggest that studies explicitly evaluating fibrin formation during in
      situ thrombin generation are warranted to explain and fully appreciate mechanisms
      of normal and abnormal fibrin clot formation in vivo.

PMID- 17208340
TI  - Biomechanical analysis of differing pedicle screw insertion angles.
AB  - BACKGROUND: Pedicle screw fixation to stabilize lumbar spinal fusion has become
      the gold standard for posterior stabilization. A significant percentage of
      surgical candidates are classified as obese or morbidly obese. For these
      patients, the depth of the incisions and soft tissue makes it extremely difficult
      to insert pedicle screws along the pedicle axis. As such, the pedicle screws can
      only be inserted in a much more sagittal axis. However, biomechanical stability
      of the angled screw insertion has been controversial. We hypothesized that the
      straight or parallel screw was a more stable construct compared to the angled or
      axially inserted screw when subjected to caudal cyclic loading. METHODS: We
      obtained 12 fresh frozen lumbar vertebrae from L3 to L5 from five cadavers.
      Schantz screws (6.0 mm) were inserted into each pedicle, one angled and along the
      axis of the pedicle and the other parallel to the spinous process. Fluoroscopic
      imaging was used to guide insertion. Each screw was then subjected to caudal
      cyclic loads of 50 N for 2000 cycles at 2 Hz. Analysis of initial damage, initial
      rate of damage, and total damage during cyclic loading was undertaken. FINDINGS:
      Average total fatigue damage for straight screws measured 0.398+/-0.38 mm, and
      0.689+/-0.96 mm for angled screws. Statistical analysis for total fatigue damage
      ratio of angled to straight screws revealed that a significant stability was
      achieved in straight-screw construct (P<0.03). INTERPRETATION: This study showed
      that straight screw insertion results in a more stable pedicle-screw construct.
      The angled screw insertion technique resulted in more scattered values of damage
      indicating that the outcome from the angled screw fixation is less predictable.
      This validates the use of this technique to implant pedicle screws across the
      axis of the pedicle (parallel to the mid sagittal line) rather than along the
      axis, and has broad implications in instrumented posterior lumbar spinal surgery.

PMID- 17208342
TI  - Professional accounts of electroconvulsive therapy: a discourse analysis.
AB  - Electroconvulsive therapy (ECT) is a socially contested psychiatric intervention.
      However, the accounts of professionals involved in its use have rarely been
      systematically investigated. This study aimed to examine the accounts of
      clinicians who have used ECT on a routine basis. Eight health professionals
      (psychiatrists, anaesthetists and psychiatric nurses from a major city in the
      United Kingdom) with experience of ECT administration were interviewed about the
      procedure. Discourse analysis was used to interpret the interview transcripts.
      Interviewees appeared to draw on a repertoire, which constructed ECT recipients
      as severely ill. This was used to support claims which had the effect of:
      defining who should receive ECT; warranting the use of urgent physical
      psychiatric treatments; reformulating distress in biological terms; and
      discounting the therapeutic value of alternative, non-physical interventions. The
      interviewees managed concerns about ECT in a variety of ways, for example by:
      rendering it as a medical procedure with concomitant risks and benefits;
      downplaying a lack of clarity over its evidence base; and undermining the
      legitimacy of criticisms. Implications of these findings are discussed.

PMID- 17208344
TI  - Stem cell test: a practical tool in toxicogenomics.
AB  - During early embryonic development, at blastocyst stage, the embryo has an outer
      coat of cells and an inner cell mass (ICM). ICM is the reservoir of embryonic
      stem (ES) cells, which are pluripotent, i.e., have the potential to differentiate
      into all cell types of the body. Cell lines have been developed from ES cells. In
      addition, there are embryonic germ (EG) cell lines developed from progenitor germ
      cells, and embryonic carcinoma (EC) cell lines developed from teratomas. These
      cell lines are being used for the study of basic and applied aspects in medical
      therapeutics, and disease management. Another potential of these cell lines is in
      the field of environmental mutagenesis. In addition to ES cells, there are adult
      stem cells in and around different organs and tissues of the body. It is now
      possible to grow pure populations of specific cell types from these adult stem
      cells. Treating specific cell types with chemical or physical agents and
      measuring their response offers a shortcut to test the toxicity in various organ
      systems in the adult organism. For example, to evaluate the genotoxicity of a
      chemical (e.g., drug or pesticide) or a physical agent (e.g., ionizing radiation
      or non-ionizing electromagnetic radiation) during embryonic development, a large
      number of animals are being used. As an alternative, use of stem cell lines would
      be a feasible proposition. Using stem cell lines, efforts are being made to
      standardize the protocols, which will not only be useful in testing the toxicity
      of a chemical or a physical agent, but also in the field of drug development,
      environmental mutagenesis, biomonitoring and other studies.

PMID- 17208343
TI  - Pathways of influence on equity in health.
AB  - An increasing number of studies are documenting the existence of inequities, and
      attention is now turning to exploring pathways through which they are generated
      and might be attacked. This appears to be an opportune time to consider what has
      been learned and what future directions might be taken by researchers to fill
      gaps in knowledge and make research more useful for policy interventions. This
      commentary briefly reviews some of the main contributions of past research that
      have possible relevance to pathways, considers what those pathways might include,
      and concludes with implications for future research. It makes the case for a
      conceptualization of influences on equity that explicitly includes distribution
      of health as an outcome as well as characteristics of the society as influences.

PMID- 17208345
TI  - Unilateral massive ovarian edema: a diagnostic dilemma.

PMID- 17208346
TI  - The effect of intraperitoneal interleukin-2 on surgically induced endometriosis
      in rats.
AB  - OBJECTIVE: To evaluate the effect of interleukin-2 (IL-2) on an experimental
      model of endometriosis. STUDY DESIGN: Double blind and randomized experimental
      prospective placebo-controlled study. Experimental endometriosis was induced in
      66 three-month-old female Wistar rats, by auto-transplanting fragments of
      endometrium to the peritoneum. After four weeks, the size of each implant was
      measured in millimeters by laparotomy (L2), and animals were randomly distributed
      for intraperitoneal administration of human-IL-2, rat-IL-2 or placebo. Four weeks
      later, the implants were measured (L3) and a second dose was given. After four
      weeks, endometriosis size was evaluated again (L4). RESULTS: We found a reduction
      of experimental endometriosis at L3 that was only significant in IL-2 treated
      groups: 20.1% and 30.3% with human-IL-2 and rat-IL-2, respectively (p<0.001 with
      respect to L2 size), versus a non-significant reduction of 9.0% found in placebo
      group, but the differences were not statistically significant between groups. The
      decrease after a second dose (L4) was: 49.8%, 41.8% and 11.4% with human-IL-2,
      rat-IL-2 and placebo, respectively (p<0.001 in IL-2 groups versus L2 and L3, and
      p<0.05 in both groups versus placebo at L4). CONCLUSION: Intraperitoneal
      administration of IL-2 reduces experimental endometriosis, and this effect is
      similar using rat-IL-2 or human IL-2 (non specie-specific effect).

PMID- 17208347
TI  - Multimodality therapy of squamous cell carcinoma arising in mature cystic
      teratoma of ovary: a case report.

PMID- 17208348
TI  - An analysis of urban development and its environmental impact on the Tampa Bay
      watershed.
AB  - Urbanization has transformed natural landscapes into anthropogenic impervious
      surfaces. Urban land use has become a major driving force for land cover and land
      use change in the Tampa Bay watershed of west-central Florida. This study
      investigates urban land use change and its impact on the watershed. The spatial
      and temporal changes, as well as the development density of urban land use are
      determined by analyzing the impervious surface distribution using Landsat
      satellite imagery. Population distribution and density are extracted from the
      2000 census data. Non-point source pollution parameters used for measuring water
      quality are analyzed for the sub-drainage basins of Hillsborough County. The
      relationships between 2002 urban land use, population distribution and their
      environmental influences are explored using regression analysis against various
      non-point source pollutant loadings in these sub-drainage basins. The results
      suggest that strong associations existed between most pollutant loadings and the
      extent of impervious surface within each sub-drainage basin in 2002. Population
      density also exhibits apparent correlations with loading rates of several
      pollutants. Spatial variations of selected non-point source pollutant loadings
      are also assessed.

PMID- 17208349
TI  - Public policy, private landholders: perspectives on policy mechanisms for
      sustainable land management.
AB  - A variety of tools can be employed in support of environmental policy objectives,
      but achieving preferred outcomes also requires the cooperation of private
      landholders and others with vested interests in the land. The Land Stewardship
      project in the state of Victoria, Australia, is an initiative devoted to
      exploring the ways in which private landholders could be encouraged towards more
      sustainable land management. Following the view that the success of policy
      initiatives is contingent on effective stakeholder engagement, a component of the
      Land Stewardship project involved a dialogue with landholders about policy tools
      (e.g., regulation, economic instruments) that might be deployed to encourage
      improved land management practices. This paper provides an account of the views
      and attitudes of landholders, as revealed in a series of three workshops, which
      consisted of discussions about the factors influencing agriculture, participants'
      interpretations of sustainability, and policy methods. The focus of the paper is
      on what landholders believe to be the strengths and limitations of standard
      policy tools, and the essential requirements for these tools to deliver the best
      land management outcomes. One of the main findings of the project was a
      'preference hierarchy' in respect of policy methods, according to which the
      strongest support was expressed for voluntary and education-based tools, followed
      by market-based instruments, with command-and-control regulation identified as a
      measure of 'last resort'. In the paper we reflect also on how the views and
      outlook of landholders should be positioned relative to other inputs in the
      design of policy interventions.

PMID- 17208350
TI  - Road effects on abundance and fitness of Galapagos lava lizards (Microlophus
      albemarlensis).
AB  - Vehicle collisions with wildlife have the potential to negatively impact species
      everywhere roads divide natural habitats; this is especially true in areas where
      roads are a recent addition to the landscape (e.g., in the last decade) and/or
      where expansion of a road network is underway. This study addresses the impact of
      traffic fatalities on lava lizards, Microlophus albemarlensis, on the island of
      Santa Cruz, Galapagos. The main road bisecting the island north to south was
      added to the island beginning in 1974 but not fully paved until 2000. We assessed
      impacts occurring due to traffic and vehicle speeds on the island. This study
      adds impacts to lizard populations to those conducted on birds on Santa Cruz,
      providing a means to create multi-species recommendations. To quantify impacts to
      lizard populations, we assessed lizards on randomly chosen transects
      perpendicular to the road. We used Poisson regression to analyze those data and
      found a 30% increase in lizard abundance per 100 m distance from the road across
      vegetation zones. We compared incidence of prior tail loss of road-killed lizards
      and live animals to comment on additional energetic costs of occupying near-road
      territories. Tail condition could not be assessed in some road-killed lizards;
      among those that we could assess, 29% showed evidence of prior tail loss. That
      rate declined to apparent baseline conditions of only 1% beyond 200 m from the
      road. By traveling the length of the 40-km road, we identified hot spots for
      fatalities of both lizards and birds to provide necessary information for
      developing management and remediation strategies. We offer guidance on Best
      Management Practices, such as testing overpasses, fencing and underpasses, which
      might reduce vehicle impacts to lizards from drivers on the current road. This
      information is essential because of a planned increase in the Santa Cruz road
      network in areas where lava lizards are most abundant.

PMID- 17208351
TI  - Blood flow occlusion via ultrasound image-guided high-intensity focused
      ultrasound and its effect on tissue perfusion.
AB  - This study investigated the induction of tissue necrosis by arterial blood flow
      occlusion using ultrasound image-guided high-intensity focused ultrasound (HIFU).
      We constructed a prototype HIFU transducer in combination with an imaging probe
      that provided color Doppler imaging and ultrasound contrast imaging. The HIFU
      beam was aimed into a branch of the renal artery in vivo. The renal artery
      branches of eight rabbits were occluded by HIFU at an intensity of 4 kW/cm(2)
      (from 2 to 10 times of each sonication for 5 s). When the HIFU exposure was
      successful, complete cessation of blood flow was observed by color Doppler
      imaging with success rate of 100% (8/8). Furthermore, lack of perfusion was
      observed in the renal cortex with a contrast-enhanced image. Postmortem
      histologic evaluation showed a wedge-shaped area of infarction in six of seven
      cases, corresponding to the lack of the contrast medium in the ultrasound image.
      These results demonstrated that ultrasound image-guided HIFU can be used to
      induce arterial occlusion, thus producing infarction and necrosis of the perfused
      tissue.

PMID- 17208352
TI  - Improved transverse flow estimation using differential maximum Doppler frequency.
AB  - Conventional Doppler technique can only provide the axial component of the blood
      flow vector, which is actually a three dimensional (3-D) quantity. To acquire the
      complete flow vector, estimations of the other two velocity components are
      essential. For the two dimensional (2-D) Doppler-bandwidth-based transverse
      estimation, however, accuracy is generally limited because of the complex
      dependence of the Doppler spectral shape on the flow variation within the sample
      volume. Two factors that may lead to the Doppler spectral change were considered
      in this study. One is the position offset of the sample volume and the other is
      the length of the sample volume. Simulations were performed and experimental data
      were also collected. Results indicate that the position offset may result in
      severe underestimation of Doppler shift frequency. Consequently, Doppler
      bandwidth is overestimated when it is determined by the difference between
      Doppler shift frequency and maximum Doppler frequency. Compared with the position
      offset, influence of the length of sample volume on the Doppler bandwidth is
      minor. To overcome this problem, a novel method, which is based on the
      differential maximum Doppler frequency, is proposed. Specifically, two beams with
      different beam widths are simultaneously generated to observe the blood flow and
      the difference between the corresponding maximum Doppler frequencies is used to
      estimate the transverse velocity. It is demonstrated that the accuracy and
      stability of transverse estimation are significantly improved by the proposed
      method even when the position offset is present.

PMID- 17208353
TI  - The determination of muscle volume with a freehand 3D ultrasonography system.
AB  - Muscle morphology determines muscle function. An objective method to determine
      muscle volume in vivo will facilitate understanding of basic muscle function and
      will also provide a valuable tool for the clinician to assess the effectiveness
      of treatment. In this method-validation study, it is hypothesised that a freehand
      3-D ultrasonography system provides a noninvasive method that allows the
      determination of muscle volume with high accuracy and precision. To test the
      hypotheses, repeated measurements were performed (1) on cadaver muscles in situ,
      (2) isolated muscles and (3) live animals. Volume measurements performed with 3-D
      ultrasonography were compared with measurements based on computed tomography and
      the water displacement method. The results of this study showed that 3-D
      ultrasound provided excellent precision and accuracy in the measurements on the
      isolated muscles and good precision in vivo. It is concluded that 3-D
      ultrasonography is an innovative technique that allows objective determination of
      muscle volume in vivo.

PMID- 17208354
TI  - The onset of ventricular isovolumic contraction as reflected in the carotid
      artery distension waveform.
AB  - The blood pressure waveform carries information about the cardiac contraction and
      the impedance characteristics of the vascular bed. Here, we demonstrate that the
      start of isovolumic ventricular contraction is persistently reflected as an
      inflection point in the pressure wave as recorded in the aortic root (TP(IC)) as
      well as in the carotid artery distension waveform (TD(IC)) as it travels down the
      arterial tree. In a group of six patients with normal pressure gradients across
      the aortic valve after valve replacement, the TP(IC) had a small delay with
      respect to the onset of isovolumic ventricular contraction (<10 ms). In a group
      (n = 21) of young presumably healthy volunteers, the inflection point occurred
      persistently in the carotid distension waveform, as recorded by means of
      ultrasound, before the systolic foot (intersubject delay between inflection point
      and systolic foot: mean +/- SD = 40.0 +/- 9.4 ms, intrasubject SD 4.6 ms).
      Retrograde coronary blood flow during isovolumic ventricular contraction may be
      the origin of the persistent end-diastolic pressure and distension perturbation.
      This study shows that the duration of the isovolumic contraction can be reliably
      extracted from the carotid artery distension waveform.

PMID- 17208355
TI  - An explicit expression for the Rayleigh-log normal probability density function.

PMID- 17208357
TI  - Protein folding and the robustness of cells.
AB  - The intricate intracellular infrastructure of all known life forms is based on
      proteins. The folded shape of a protein determines both the protein's function
      and the set of molecules it will bind to. This tight coupling between a protein's
      function and its interconnections in the molecular interaction network has
      consequences for the molecular course of evolution. It is also counter to human
      engineering approaches. Here we report on a simulation study investigating the
      impact of random errors in an abstract metabolic network of 500 enzymes. Tight
      coupling between function and interconnectivity of nodes is compared to the case
      where these two properties are independent. Our results show that the model
      system under consideration is more robust if function and interconnection are
      intertwined. These findings are discussed in the context of nanosystems
      engineering.

PMID- 17208356
TI  - Phase-II study of docetaxel, estramustine phosphate, and carboplatin in patients
      with hormone-refractory prostate cancer.
AB  - OBJECTIVES: To determine the safety and efficacy of combination chemotherapy with
      docetaxel (DTX), estramustine phosphate (EMP), and carboplatin (CBDCA) in
      patients with hormone-refractory prostate cancer (HRPC). METHODS: This study
      included a total of 40 HRPC patients. We evaluated the activity of the following
      schedule: weekly DTX 30 mg/m(2) iv, daily EMP 10mg/kg po, and CBDCA AUC=6 iv on
      day 1 of a every 4-wk cycle. Treatment was continued until disease progression or
      excessive toxicity. RESULTS: All patients were assessable for response. A median
      of six consecutive cycles was administered per patient. Levels of prostate
      specific antigen decreased by more than 50% in 95.0% of the patients. Consumption
      of medication for cancer-induced pain was reduced in 84.6%. Partial response was
      attained in 66.7% of measurable lesions. Of patients with bone metastasis, 8.3%
      demonstrated partial response. With a median follow-up of 11.4 mo, the median
      time to progression was 12.0 mo, and the median overall survival time was 26.6
      mo. The predominant toxicities were grade-3 or -4 anemia in 32.5% of the
      patients, leukopenia in 20.0%, and thrombocytopenia in 17.5%. However, all
      toxicity was temporary and reversible with dose reduction or temporary cessation
      of chemotherapeutic agents. There were no therapy-related deaths. CONCLUSIONS:
      Combination chemotherapy with DTX/EMP/CBDCA was found to have significant
      clinical activity with an acceptable toxicity profile in HRPC patients. More
      suitable selection of patients may be beneficial in terms of improved overall
      survival in the future.

PMID- 17208358
TI  - Spontaneous activity of living cells.
AB  - The purpose of this article is to give a theoretical framework to describe the
      mechanism of internal signal generation and discuss the physiological
      significance of spontaneous activities of certain living cells [Oosawa, F., 2001.
      Spontaneous signal generation in living cells. Bull. Math. Biol. 63, 643].

PMID- 17208359
TI  - Genetic programs that regulate testicular and ovarian development.
AB  - The gonadal primordium is the only tissue in mammals that has two divergent
      developmental fates leading ultimately to the formation of either a testis or an
      ovary. The goal of this review is to summarize the major characteristics of the
      male and female transcriptional programs triggered in the developing mouse gonads
      during the critical time window of sex determination. Expression profiling
      studies reveal that both male and female genetic programs are initiated as early
      as embryonic day (E) 11.5. By E13.5, more than 1000 genes are overexpressed
      either in developing ovaries or testes. A large fraction of these have so far no
      known roles during gonadal differentiation, yet interestingly some of their human
      orthologues map to chromosomal loci associated with sexual disorders. Identifying
      the functional roles for these candidate genes will improve our understanding of
      sex determination and provide new insights into the causes of gonadal dysgenesis
      and reproductive disorders.

PMID- 17208360
TI  - Adrenal cholesterol utilization.
AB  - There are multiple systems for cellular cholesterol delivery for steroidogenesis,
      including uptake of lipoprotein-derived cholesterol via LDL receptor mediated
      endocytic pathways and SR-BI mediated "selective" pathways, as well as from
      endogenous cholesterol synthesis and the mobilization of stored cholesteryl
      esters. The vast majority of lipoprotein-derived cholesterol utilized for murine
      adrenal steroidogenesis is obtained via SR-BI mediated "selective" uptake of
      cholesteryl esters. Hormone-sensitive lipase (HSL) is responsible for neutral
      cholesteryl ester hydrolase activity in the adrenal and is critical for
      hydrolyzing stored cholesteryl esters, as well as cholesteryl esters that are
      selectively delivered from lipoproteins via SR-BI. Marked defects in steroid
      production are observed in adrenal cells from HSL knockout mice, due to an
      inability to process and utilize cholesteryl esters selectively derived from
      lipoproteins. Although the LDL receptor is responsible for receptor-mediated
      endocytic delivery of cholesteryl esters, adrenal steroid hormone production is
      normal in mice lacking LDL receptors.

PMID- 17208361
TI  - Role of Agouti-related protein in adrenal steroidogenesis.
AB  - The levels of Agouti-related protein (AgRP) mRNA in the adrenal are second only
      to those in the hypothalamus, raising questions regarding its target binding
      sites and its specific role in adrenal steroidogenesis. We and others
      demonstrated the presence of a population of melanocortin receptor-4 (MC4R)
      positively coupled to steroidogenesis in adrenal cells. Moreover, AgRP inhibited
      both the acute and long-term steroidogenic responses of these cells to NDP
      alphaMSH through its antagonistic properties towards MC4R. Although AgRP had no
      antagonistic properties towards the MC2R and did not modify the acute
      steroidogenic response to ACTH, it exerted a biphasic sustained inhibitory effect
      on the long-term response to ACTH through an undefined alternate mechanism. Since
      adrenal cells release a relatively large amount of AgRP, this protein likely
      exerts a local paracrine/autocrine control on adrenal steroidogenesis.

PMID- 17208362
TI  - Role of the nuclear receptors for oxysterols LXRs in steroidogenic tissues:
      beyond the "foie gras", the steroids and sex?
AB  - Various physiological functions have been ascribed to the liver X receptors
      (LXRs). Recently, we have identified new functions of these nuclear receptors in
      steroidogenic tissues. In adrenal, LXRalpha prevents accumulation of free
      cholesterol in mouse by controlling expression of genes involved in all aspects
      of cholesterol utilization. Under chronic dietary stress, adrenals from LXR
      deficient mice accumulate free cholesterol while wild-type animals maintain
      cholesterol homeostasis through basal regulation of cholesterol efflux and
      storage. Hence, LXRalpha provides a safety valve to limit free cholesterol levels
      as a basal protective mechanism in the adrenal. Beside, mice lacking LXRalpha
      show lower levels of testicular testosterone while wild-type mice treated with
      the specific LXR agonist present an increase of testosterone production.
      Altogether, these data identify new roles for LXRs, in the regulation of
      cholesterol homeostasis in steroidogenic tissues and hormone synthesis.

PMID- 17208363
TI  - Gene polymorphisms of folate metabolizing enzymes and the risk of gastric cancer.
AB  - Multiple studies have reported an association between disturbances of folate
      metabolism and increased risk of gastric cancer, including low intake of folate,
      low levels of folate in blood or genetic factors affecting folate metabolism.
      Among the genetic factors, in particular a common polymorphism in the gene
      encoding for 5,10-methylenetetrahydrofolate reductase (MTHFR C677T) has been
      linked to gastric cancer. Other polymorphisms in folate-metabolising genes have
      been less frequently investigated. Therefore, we analyzed this polymorphism, the
      glutamate carboxypeptidase (GCP) II C1561T and the reduced folate carrier (RFC)
      G80A in a case-control study involving 106 patients with histologically confirmed
      and characterized gastric cancer with adjustment for other established risk
      factors for gastric cancer in comparison to 106 age- and sex-matched controls.
      Neither the MTHFR nor the GCP gene polymorphisms showed an association to cancer
      diagnosis, to tumor stage, grade of differentiation or Lauren type. However, non
      cardia cancers were more likely to exhibit the 80GA and 80AA RFC genotypes,
      compared to cancers of the gastric cardia (adjusted OR 0.28; 95% CI=0.11-0.71).
      Thus, gene polymorphisms of the RFC gene might contribute to an increased risk of
      developing distal gastric cancer.

PMID- 17208364
TI  - Adsorptive removal of Methylene blue and Methyl orange from aqueous media by
      carboxylated diaminoethane sporopollenin: on the usability of an aminocarboxilic
      acid functionality-bearing solid-stationary phase in column techniques.
AB  - The adsorption phenomena of Methylene blue (MB) and Methyl orange (MO) on a
      carboxylated diaminoethane sporopollenin (CDAE-S) solid phase were investigated
      in a column arrangement by using breakthrough technique. The adsorption phenomena
      were evaluated using some common adsorption isotherm models and Scatchard plot
      analysis, and obtained results were interpreted for evaluating the usability of
      CDAE-S for removal, recovery and preconcentration of the studied dyes both at the
      laboratory and industrial scales. On the basis of Scatchard plot analysis, the
      interaction types between the CDAE-S and the studied dyes were criticized in
      terms of affinity phenomena. Thus, the usability of a biomacromolecule-derived
      material, CDAE-S, as a cheap, environmentally-friendly and effective solid
      stationary phase exhibiting both cation-exchange and anion-exchange
      characteristics at the same time, is discussed through the present study.
      Besides, from the obtained results, the protonated CDAE-S, which functionally
      resembles an amino acid structure, are presented as a two-in-one solid-stationary
      phase, and its adaptability to common processes performed under column conditions
      is also drawn in detail.

PMID- 17208365
TI  - Site-specific health risk assessment of dioxins and furans in an industrial
      region with numerous emission sources.
AB  - While the sources of releasing dioxins have received much attention, the health
      risks of incinerators are studied considerably more than those of other sources,
      such as metallurgical industry. Furthermore, risk assessments focus primarily on
      the effects of single sources; few have addressed the aggregate risks from
      multiple sources in a region. When many sources of dioxins exist in an area, such
      as the Industrial Park located in the densely populated district-Siaogang
      District in southern Taiwan where 17 primary known PCDD/F stationary emission
      sources are clustered, is the aggregate exposure to these sources imposing high
      risks even though individual sources comply with emission standards? The study
      combined the multimedia and multiple pathway exposure modeling and site-specific
      exposure scenario to assess dioxin risks contributed by the 17 emission sources
      in the District, including municipal waste incinerators, medical waste
      incinerators, sinter plants, electric arc furnace, secondary aluminum smelters,
      cement kilns, etc. The average cancer risk of a resident living in the District
      was found to be 3.43E-04 under the site-specific exposure scenario. The top
      emission source is the sinter plant, followed by the electric arc furnace. The
      information has driven the local government to conduct more complete assessment
      and at the same time to consider enforcing a stricter local standard of dioxin
      emissions in the Siaogang District.

PMID- 17208366
TI  - Adsorption of benzene and toluene from aqueous solutions onto activated carbon
      and its acid and heat treated forms: influence of surface chemistry on
      adsorption.
AB  - The influence of surface chemistry and solution pH on the adsorption of benzene
      and toluene on activated carbon and its acid and heat treated forms were studied.
      A commercial coal-based activated carbon F-400 was chosen as carbon parent. The
      carbon samples were obtained by modification of F-400 by means of chemical
      treatment with HNO3 and thermal treatment under nitrogen flow. The treatment with
      nitric acid caused the introduction of a significant number of oxygenated acidic
      surface groups onto the carbon surface, while the heat treatment increases the
      basicity of carbon. The pore characteristics were not significantly changed after
      these modifications. The dispersive interactions are the most important factor in
      this adsorption process. Activated carbon with low oxygenated acidic surface
      groups (F-400Tox) has the best adsorption capacity.

PMID- 17208367
TI  - Physical and oxidative removal of organics during Fenton treatment of mature
      municipal landfill leachate.
AB  - Municipal landfill leachate, especially mature leachate, may disrupt the
      performance of moderately-sized municipal activated sludge wastewater treatment
      plants, and likewise tend to be recalcitrant to biological pretreatment.
      Recently, Fenton methods have been investigated for chemical treatment or pre
      treatment of mature leachate. In this paper, the results of laboratory tests to
      determine the roles of oxidation and coagulation in reducing the organic content
      of mature leachate during Fenton treatment are presented. The efficiencies of
      chemical oxygen demand (COD) oxidation and coagulation were tested, and the ratio
      of COD removal by oxidation to that by coagulation was assessed, under various
      operating conditions. Low initial pH, appropriate relative and absolute Fenton
      reagent dosages, aeration, and stepwise addition of reagents increased COD
      removal by oxidation and the importance of oxidation relative to coagulation.
      Simultaneous aeration and stepwise reagent addition allowed comparable treatment
      without initial acidification pH, due to the generation of acidic organic
      intermediates and the continuous input of CO2. On the other hand, high COD
      oxidation efficiency and low ferrous dosage inhibited COD removal by coagulation.
      At significantly high oxidation efficiency, overall COD reduction decrease
      slightly due to low coagulation efficiency. Under the most favorable conditions
      (initial pH 3, molar ratio [H(2)O(2)]/[Fe2+]=3, [H2O2]=240 mM, and six dosing
      steps), 61% of the initial COD was removed, and the ratio of COD removal
      oxidation to coagulation was 0.75. Results highlighted the synergistic roles of
      oxidation and coagulation in Fenton treatment of mature leachate, and the role of
      oxidation in controlling the efficiency of removal of COD by coagulation.

PMID- 17208368
TI  - Enhancing struvite precipitation potential for ammonia nitrogen removal in
      municipal landfill leachate.
AB  - This study was conducted to improve struvite precipitation for NH4-N removal
      purpose in landfill leachate. For this purpose, we evaluated the effect of the
      feeding sequence of precipitating reagents (magnesium, orthophosphate, and
      buffering reagent) on NH4-N removal by forming struvite deposits. Struvite
      precipitation effectively proceeded by an addition of excess magnesium and
      phosphate sources followed by an addition of the buffering reagent, in which
      condition the local formation of inappropriate deposits or the contamination of
      the desired struvite was minimized. We also tested the effect of struvite
      addition as the seeding materials on NH4-N removal. Seed addition would increase
      the potential for the struvite crystal growth, which enhanced NH4-N removal
      performance in landfill leachate treatment.

PMID- 17208369
TI  - Application of iron-rich natural clays in Camlica, Turkey for boron sorption from
      water and its determination by fluorimetric-azomethine-H method.
AB  - In this study, iron-rich natural Camlica Bentonites, CB1 and CB2, were used for
      the sorption of boron in water samples. Boron was determined by newly progressed
      fluorimetric azomethine-H method. The optimum conditions found using factorial
      designs are pH 10, 45 degrees C, 0.250 g of clay and 20 mL of sample volume. It
      was found that 180 min is enough time for the equilibrium state to be reached in
      boron adsorption. At these conditions, boron sorption percentage was 80% for CB1
      and 30% for CB2. The adsorption isotherms are well described by linear Freundlich
      model. Various geothermal waters in our country were also studied for boron
      sorption.

PMID- 17208370
TI  - Characterization of red mud derived from a combined Bayer Process and bauxite
      calcination method.
AB  - Red mud can be derived from the processing of bauxite using different methods.
      The chemical and mineralogical composition of the combined Bayer Process and
      bauxite calcination red mud (BPBCRM) differs markedly from those of the pure
      Bayer Process red mud (PBPRM). In this study, red mud derived from a combined
      Bayer Process and bauxite calcination method was characterized. The results show
      that pH of the red mud decreased with increasing duration of storage time. Na
      dominated among the soluble cations, but the concentration of soluble Na
      decreased with increasing duration of storage time as a result of leaching.
      Cation exchange capacity also decreased with increasing duration of storage time,
      probably due to a decrease in pH causing a reduction in negatively charged sites
      on the red mud particles. Ca was the predominant exchangeable cation in the fresh
      red mud but the concentration of exchangeable Ca markedly decreased in the old
      red mud, which was dominated by exchangeable Na. The degree of crystallization
      and thermal stability of the red mud increased with increasing duration of
      storage. The acid neutralizing capacity of red mud obtained from this study was
      about 10 mol kg(-1), which is much greater than the reported values for the pure
      Bayer Process red mud. Column filtering experiment indicates that the red mud
      also had a very strong capacity to remove Cu, Zn and Cd from the filtering
      solution. It is conservatively estimated that the simultaneous removal rates of
      Cd, Zn and Cu by red mud are over 22,250 mg kg(-1), 22,500 mg kg(-1) and 25,000
      mg kg(-1), respectively. The affinity of these metals to the red mud was in the
      following decreasing order: Cu>Zn>Cd. In general, the fresh red mud retained more
      heavy metals than the old red mud did.

PMID- 17208371
TI  - Source apportionment of PM2.5 in Beijing in 2004.
AB  - Based on measurements of fine particulate matter (PM2.5, i.e., particles with an
      aerodynamic diameter of 2.5 microm or less) in January and August 2004, serious
      air pollution persists in Beijing. The chemical analysis included organic and
      elemental carbon, water-soluble ions, and elemental compositions. The positive
      matrix factorization (PMF) method was used to apportion the PM2.5 sources. The
      sources contributing dominantly to PM2.5 mass concentrations are coal combustion
      in winter and the secondary products in summer. Furthermore, the contributions
      from motor vehicles, road dusts and biomass burning could not be neglected. The
      products of biomass burning for winter heating in the area around Beijing could
      enter the urban area during quasi-quiescent weather conditions. In conclusion,
      some effective control measures were proposed to reduce the PM2.5 pollution in
      Beijing.

PMID- 17208373
TI  - Generators of the gamma-band activities in response to rare and novel stimuli
      during the auditory oddball paradigm.
AB  - In this study, we report the cortical sources of the gamma-band activity emitted
      during the auditory oddball paradigm using the adaptive beamformer algorithm and
      non-parametric permutation test and then compare them with those of the P3a and
      P3b components. The results of the gamma-band current sources revealed that the
      same gamma-band activities are in process during the rare target and novelty
      task. In the low (30-55 Hz) gamma-band activity, the common sources were
      localized in the (inferior) anterior cingulate and adjacent inferior frontal
      cortex. In the high (65-85 Hz) gamma-band activity, the generator was represented
      in the superior frontal cortex. On the other hand, the P3a and P3b generators
      showed widespread distributions including the well-known fronto-parietal network
      [J. Polich, Theoretical overview of P3a and P3b, in: J. Polish (Ed.), Detection
      of Change: Event-Related Potential and fMRI Findings, Kluwer Academic Press,
      Boston, 2003, pp. 83-98]. In conclusion, the same frontal generators of gamma
      band activities in the present study may be associated with the functions of
      attentional control for the binding of consecutive cognitive stages corresponding
      to earlier P3a and later P3b components, which have distinct source distributions
      except for some overlaps.

PMID- 17208372
TI  - Solid phase extraction method for the determination of lead, nickel, copper and
      manganese by flame atomic absorption spectrometry using sodium bispiperdine-1,1'
      carbotetrathioate (Na-BPCTT) in water samples.
AB  - A novel column solid phase extraction procedure was developed for the
      determination of lead, nickel, copper and manganese in various water samples by
      flame atomic absorption spectrometry (FAAS) after preconcentration on sodium
      bispiperdine-1,1'-carbotetrathioate (Na-BPCTT) supported by Amberlite XAD-7. The
      sorbed element was subsequently eluted with 1M nitric acid and the acid eluates
      are analysed by Flame atomic absorption spectrometry (FAAS). Various parameters
      such as pH, amount of adsorbent, eluent type and volume, flow-rate of the sample
      solution, volume of the sample solution and matrix interference effect on the
      retention of the metal ions have been studied. The optimum pH for the sorption of
      above mentioned metal ions was about 6.0+/-0.2. The loading capacity of adsorbent
      for Pb, Cu, Ni and Mn were found to 28, 26, 22 and 20x10(-6) g/mL, respectively.
      The recoveries of lead, copper, nickel and manganese under optimum conditions
      were found to be 96.7-99.2 at the 95% confident level. The limit of detection was
      3.0, 3.2, 2.8 and 3.6x10(-6) g/mL for lead, copper, nickel and manganese,
      respectively by applying a preconcentration factor 50. The proposed enrichment
      method was applied for metal ions in various water samples. The results were
      obtained are good agreement with reported method.

PMID- 17208374
TI  - High-cholesterol feeding aggravates cerebral infarction via decreasing the CB1
      receptor.
AB  - We examined how feeding conditions affect the CB1 receptor and cerebral
      infarction caused by cerebral ischemia. Mice were divided into the following
      three groups: normal diet (ND), caloric restriction (CR) and high-cholesterol
      enriched diet (HCD), and were kept for 6 weeks. After 6 weeks, we measured both
      serum and brain cholesterol and the expression level of cannabinoid CB1 receptor
      within the brain in intact mice. In addition, middle cerebral artery (MCA) was
      occluded for 2 h following reperfusion. Serum cholesterol significantly increased
      in the HCD group in comparison with both the ND and CR groups. However, brain
      cholesterol decreased in the HCD group. Then, the expression level of CB1
      receptor significantly decreased in the HCD group, while that of the CR group
      clearly increased in comparison with the ND group in intact mice. In MCA-occluded
      mice, The HCD group produced the most severe cerebral infarction, while cerebral
      infarction was significantly decreased in the CR group. These results suggest
      that CR prevents infarction by increasing CB1 receptor expression, while high
      cholesterol feeding aggravates cerebral infarction both by hypercholesterolemia
      in serum and by decreasing CB1 receptor expression modulated by
      hypocholesterolemia within the brain.

PMID- 17208376
TI  - Attention shortage resistance of negative stimuli in an implicit emotional task.
AB  - Considerable evidence from behavioral studies has indicated that people tend to
      pay attention to negative stimuli preferentially. The attentional bias can occur
      rapidly and automatically. In the current study, a 'cue-target' paradigm was
      utilized to manipulate the attention allocation. Seventeen healthy undergraduates
      participated in the experiment. The stimuli were emotional pictures (positive,
      neutral and negative), which were upper and lower adjacent patchworks of a normal
      scene and its inverted copy. The subjects should judge whether the normal scene
      (compared with the inverted scene) was located in the upper or lower part of the
      whole patchwork. We used this implicit emotional task to avoid the task relevance
      effect. It was found that the amplitude of P2 waves was enlarged by the negative
      pictures and there was a significant interaction between the cue effect and the
      emotional valence. We can conclude that the negative information exerts an
      attentional bias effect in the emotional perception, and that the negative
      contents suffer less in the insufficient attention condition compared with the
      positive and the neutral conditions.

PMID- 17208375
TI  - Gene-gene interaction analysis of personality traits in a Japanese population
      using an electrochemical DNA array chip analysis.
AB  - It has been suggested that genes involved in the central dopaminergic pathway may
      contribute to personality traits. However, the results of association studies for
      these genes have not been consistent. The present study investigated the
      relationship between the specific polymorphisms of MAO-A, COMT, DRD2, DRD3 and
      personality traits in Japanese women using a novel genotyping method involving
      electrochemical DNA array (ECA) chip analysis. Single marker association analysis
      for each mutation revealed no significant association between scores for
      Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) items. Gene
      gene interaction analysis showed that a MAO-A 30-bp repeatxCOMT (Val158Met)xDRD3
      (Ser9Gly) had a marginally significant association with Agreeableness (P=0.0547).
      The present results suggest that a combination of polymorphisms of MAO-A, COMT,
      and DRD3 might affect personality traits in Japanese women.

PMID- 17208377
TI  - Genotyping of Babesia bigemina from cattle from a non-endemic area (Switzerland).
AB  - In August 2002, bovine anaplasmosis and concurrent infections with Mycoplasma sp.
      and piroplasms were reported in a cattle herd in an alpine region of Switzerland.
      The piroplasms were identified by PCR/sequencing of part of the 18S rRNA gene as
      Babesia bigemina and Theileria of the buffeli/sergenti/orientalis-complex, which
      have never been diagnosed in Switzerland before. The B. bigemina isolate was
      genetically characterised at two loci and compared with isolates from Italy,
      Spain, Turkey, Kenya and Mexico. Analysis of the internal transcribed spacer 2
      (ITS2) of the rRNA genes revealed high polymorphism not only among the isolates
      but even within the isolates, and the presence of two types of the ITS2 in every
      isolate was confirmed. A dendrogram based on ITS2 sequences showed that the Swiss
      isolate was most closely related to a Spanish isolate but no sequences of the
      isolate from Switzerland were identical to any of the other isolates. The isolate
      from Italy was not positioned in the same cluster as the Swiss and the Spanish
      isolate. This had been anticipated as the nearest known endemic area of B.
      bigemina in Central Italy. Sequence analysis of the rhoptry-associated protein-1c
      gene (rap1c) confirmed the similarity of the Swiss and Spanish isolate. Hence,
      our molecular analyses of the Swiss B. bigemina isolate did not unequivocally
      track its geographical origin and the way of introduction remains obscure.

PMID- 17208378
TI  - Studies on some trematode parasites of stray dogs in Egypt with a key to the
      identification of intestinal trematodes of dogs.
AB  - Fourteen of 30 stray dogs examined from Ismailia City, Egypt were infected with
      one or more species of intestinal trematodes, including Mesostephanus
      appendiculatus, Mesostephanus milvi, Mesostephanus fajardensis, Echinochasmus
      liliputanus, Heterophyes dispar, and Pygidiopsis genata. The morphology of each
      species was compared with earlier descriptions and a key to the identification of
      canine intestinal trematodes in this geographic region was developed.

PMID- 17208379
TI  - Association of the bovine leukocyte antigen major histocompatibility complex
      class II DRB3*4401 allele with host resistance to the Lone Star tick, Amblyomma
      americanum.
AB  - The MHC of cattle, known as the bovine leukocyte antigen (BoLA) complex, plays an
      integral role in disease and parasite susceptibility, and immune responsiveness
      of the host. While susceptibility to tick infestation in cattle is believed to be
      heritable, genes that may be responsible for the manifestation of this phenotype
      remain elusive. In an effort to analyze the role that genes within the BoLA
      complex may play in host resistance to ticks, we have evaluated components of
      this system within a herd of cattle established at our laboratory that has been
      phenotyped for ectoparasite susceptibility. Of three microsatellite loci within
      the BoLA complex analyzed, alleles of two microsatellite loci within the BoLA
      class IIa cluster (DRB1-118 and DRB3-174) associated with the tick-resistant
      phenotype, prompting further investigation of gene sequences within the DRB3
      region. DRB3 is a class IIa gene, the second exon of which is highly polymorphic
      since it encodes the antigen recognition site of the DR class II molecule.
      Analysis of the second exon of the DRB3 gene from the phenotyped calves in our
      herd revealed a significant association between the DRB3*4401 allele and the tick
      resistant phenotype. To our knowledge, this is the first report of a putative
      association between a class IIa DRB3 sequence and host resistance to the Lone
      Star tick. Elucidation of the mechanism involved in tick resistance will
      contribute to improving breeding schemes for parasite resistance, which will be
      beneficial to the cattle industry.

PMID- 17208380
TI  - Vitamin B6 suppresses apoptosis of NM-1 bovine endothelial cells induced by
      homocysteine and copper.
AB  - Hyperhomocysteinemia is an important risk factor for atherosclerosis. We
      previously reported that formation of early atherosclerosis in the rat aorta was
      associated with hyperhomocysteinemia and reduction of antioxidant activity caused
      by low concentration of vitamin B(6)in vivo. In the present study, we examined
      effects of vitamin B(6) on apoptosis of bovine endothelial cells (NM-1 cells)
      treated with homocysteine and copper. Homocysteine and copper induced
      extracellular hydrogen peroxide, intracellular ROS and cellular lipid peroxide
      levels. Cell viability was reduced to 30% compared to that of control cells. On
      the other hand, pyridoxal treatment as well as EDTA treatment increased viability
      of NM-1 cells treated with homocysteine and copper to about 60%, and
      significantly decreased extracellular hydrogen peroxide, intracellular ROS and
      cellular lipid peroxide levels. The treatment of catalase recovered cell
      viability and reduced the level of extracellular hydrogen peroxide and
      intracellular ROS. Cell death by homocysteine and copper was confirmed to be due
      to apoptosis by evaluation of DNA fragmentation and by TUNEL assay. However,
      apoptosis of NM-1 cells induced by homocysteine and copper was due to a caspase
      independent pathway as it was not inhibited by the caspase inhibitor, Z-VAD-fmk.
      Apoptosis of NM-1 cells induced by homocysteine and copper accompanied with
      mitochondrial permeability but not cytochrome c release. These results suggest
      that pyridoxal treatment suppresses apoptosis of NM-1 cells induced by
      homocysteine and copper, most likely through antioxidant effects.

PMID- 17208382
TI  - Analysis of clinical symptomatology, extrapyramidal symptoms and neurocognitive
      dysfunction following dehydroepiandrosterone (DHEA) administration in olanzapine
      treated schizophrenia patients: a randomized, double-blind placebo controlled
      trial.
AB  - Several studies have demonstrated the effective use of dehydroepiandrosterone
      (DHEA) in the management of mood, however studies of its use in psychosis remain
      limited. The aim of this study was to investigate for the first time efficacy of
      DHEA augmentation with standardized antipsychotic medication (olanzapine) and to
      explore effects of DHEA augmentation on side-effect profiles including weight
      gain, glucose tolerance, aggression, quality of life and neurocognitive function.
      Finally, we aimed to analyze any relationship between plasma levels and clinical
      response to DHEA administration. Forty patients with chronic schizophrenia
      stabilized on olanzapine were randomized in double-blind fashion to receive
      either DHEA (titrated up to 150mg) or placebo augmentation for a period of 12
      weeks. Blood samples were collected at baseline, mid-study and study completion.
      Results indicated improvement of negative symptoms (SANS scale) even when
      baseline scores were controlled as a covariate. Some improvement in Parkinsonism
      and akathisia compared to baseline was seen in patients receiving DHEA. No change
      in psychosis as reflected by the PANSS was noted. Patients receiving DHEA
      appeared to demonstrate relatively stable glucose levels compared to controls at
      the end of the study. An improvement in cognitive performance (most notably
      memory), which did not reach significance due to low sample number, was observed
      following DHEA administration. Results further suggest preliminary evidence of
      involvement of the neurosteroid system in schizophrenia pathophysiology, and
      confirm initial "cautious" findings identifying an agent capable of improving
      negative symptoms and certain features of extrapyramidal side effects.

PMID- 17208383
TI  - Pathomolecular effects of homocysteine on the aging process: a new theory of
      aging.
AB  - Homocysteine has been associated with the most common age-related diseases but
      never associated with the acceleration of the aging process. This theoretical
      paper will try to demonstrate the pro-aging effects of homocysteine at the
      molecular, cellular, and organ level. High homocysteine levels in homocystinuria
      are associated with premature disease of the cardiovascular, skeletal,
      neurological, and other systems. These observations are similar to those noted in
      the aging process and should be considered as a progeroid syndrome. There is
      enough scientific evidence to support that homocysteine accelerates the aging
      process at the cellular and at the organism level. Most importantly, decreasing
      homocysteine levels by dietary or pharmacological interventions could prolong
      maximum life span in humans and/or delay the onset of the most common age-related
      diseases.

PMID- 17208381
TI  - The origin of the skewed amplitude distribution of spontaneous excitatory
      junction potentials in poorly coupled smooth muscle cells.
AB  - The skewed amplitude distribution of spontaneous excitatory junction potentials
      (sEJPs) in the mouse vas deferens and other electrically-coupled smooth muscle
      syncytia has been attributed to electrically-attenuated depolarizations resulting
      from the spontaneous release of quantized packets of ATP acting on remote smooth
      muscle cells (SMCs). However, in the present investigation surface SMCs of the
      mouse isolated vas deferens were poorly electrically coupled, with input
      resistances (176+/-18 MOmega, range: 141-221 MOmega, n=4) similar to those of
      dissociated cells. Furthermore, the amplitude of evoked EJPs was more variable in
      surface compared with deeper SMCs (F test, F=17.4, P<0.0001). Using simultaneous
      electrophysiology and confocal microscopy to investigate these poorly-coupled
      cells, it is shown that alpha-latrotoxin-stimulated sEJPs correlate, in timing
      (median delay ranged from -30 to -57 ms, P<0.05 in all experiments, n=5) and
      amplitude (Pearson product moment correlation, rho>0.55 and P<0.001), with
      purinergic neuroeffector Ca2+ transients (NCTs) in SMCs. The temporal correlation
      between sEJPs of widely ranging amplitude with NCTs in the impaled SMC
      demonstrates that all sEJPs could arise from neurotransmitter action on the
      impaled cell and that the skewed distribution of sEJPs can be explained by the
      variable effect of packets of ATP on a single SMC. The amplitude correlation of
      sEJPs and NCTs argues against the attenuation of electrical signal amplitude
      along the length of a single SMC. The skewed sEJP amplitude distribution arising
      from neurotransmitter release on single SMCs is consistent with a broad
      neurotransmitter packet size distribution at sympathetic neuroeffector junctions.

PMID- 17208384
TI  - Adipokines regulate systemic insulin sensitivity in accordance to existing energy
      reserves.
AB  - Adipocyte-derived hormones, including adiponectin and leptin, regulate systemic
      insulin sensitivity in accordance to existing triglyceride reserves. Leptin
      levels reflect existing fat mass and the adipokine negatively regulates insulin
      action in adipose tissue. Adiponectin, on the other hand, preserves insulin
      sensitivity via transient increments of AMPK activity and its circulating levels
      seem to reflect the adipogenic capacity of adipose tissue. Because adiponectin
      and insulin synergize in their postprandial actions, it seems evident that
      inadequate adiponectin production causes systemic insulin resistance. As a
      consequence, compounds that either increase adiponectin production or mimic its
      actions can be considered as an efficient strategy for improving insulin
      sensitivity in type 2 diabetics. We have previously shown that troglitazone and
      metformin exert opposing actions on adiponectin production, indicating that
      combined use of troglitazone and metformin is a more efficient strategy as
      compared to metformin treatment. Here, we will provide additional arguments which
      stress the need for a fixed dose of troglitazone and metformin in order to
      preserve endogenous adiponectin production. Finally, after delineating critical
      nodes of insulin and adipokine crosstalk, putative pathways are proposed by which
      adiponectin and leptin cooperatively regulate systemic insulin sensitivity in
      accordance to existing fat mass. By amplifying insulin action downstream of PI3K,
      leptin exerts negative feedback on insulin signaling via mTOR-dependent pathways
      that target IRS-1 for serine phosphorylation and protein degradation. Adiponectin
      mediated increments of AMPK activity, on the other hand, may attenuate mTOR
      signaling, leading to the preservation of insulin sensitivity in periods of
      increased nutrient availability. Considering that leptin and adiponectin are
      inversely associated with BMI, the proposed model provides a plausible
      explanation for the observation that leptin exerts strong negative feedback on
      systemic insulin sensitivity, while increasing PIP3 availability.

PMID- 17208385
TI  - An assessment of PTV margin definitions for patients undergoing conformal 3D
      external beam radiation therapy for prostate cancer based on an analysis of
      10,327 pretreatment daily ultrasound localizations.
AB  - INTRODUCTION: We have assessed the planning target volume (PTV) margins required
      for adequate treatment of the prostate in the absence of daily localization
      imaging based on the statistical analysis of a large data set obtained from 5
      years of use of a two-dimensional ultrasound pretreatment localization device.
      METHODS AND MATERIALS: Data from 387 prostate patients were analyzed
      retrospectively. Every patient in the study received daily pretreatment
      localization resulting in a total of 10,327 localizations, each comprising an
      isocenter displacement in three directions: anteroposterior, right-left lateral,
      and superior-inferior. The mean displacement for each direction for each patient
      was computed from daily treatment records, and a mean of the means was used in
      the analysis. RESULTS: The mean displacements required to shift the target to the
      required position were 6.1 mm posterior (4.4 mm SD), 2.1 mm superior (4.5 mm SD),
      and 0.5 mm right (3.6 mm SD). The 6.1-mm shift posterior is indicative of a
      systematic uncertainty. Differences in planning conditions between the computed
      tomography simulation and the treatment room may account for this discrepancy.
      CONCLUSION: Our study has revealed systematic intertreatment uncertainties that
      would have required a nonuniform PTV margin ranging in dimensions between 2.7 mm
      anterior, 14.9 mm posterior, 7.7 mm right, 6.7 mm left, 11 mm superior, and 7 mm
      inferior to encompass the prostate for 95% of our sample if the ultrasound
      localization system were not used. In the absence of systematic uncertainties, a
      uniform PTV margin of 9 mm would suffice.

PMID- 17208386
TI  - An evaluation of the variability of tumor-shape definition derived by experienced
      observers from CT images of supraglottic carcinomas (ACRIN protocol 6658).
AB  - PURPOSE: Accurate target definition is considered essential for sophisticated,
      image-guided radiation therapy; however, relatively little information has been
      reported that measures our ability to identify the precise shape of targets
      accurately. We decided to assess the manner in which eight "experts" interpreted
      the size and shape of tumors based on "real-life" contrast-enhanced computed
      tomographic (CT) scans. METHODS AND MATERIALS: Four neuroradiologists and four
      radiation oncologists (the authors) with considerable experience and presumed
      expertise in treating head-and-neck tumors independently contoured, slice-by
      slice, his/her interpretation of the precise gross tumor volume (GTV) on each of
      20 sets of CT scans taken from 20 patients who previously were enrolled in
      Radiation Therapy Oncology Group protocol 91-11. RESULTS: The average proportion
      of overlap (i.e., the degree of agreement) was 0.532 (95% confidence interval
      0.457 to 0.606). There was a slight tendency for the proportion of overlap to
      increase with increasing average GTV. CONCLUSIONS: Our work suggests that
      estimation of tumor shape currently is imprecise, even for experienced
      physicians. In consequence, there appears to be a practical limit to the current
      trend of smaller fields and tighter margins.

PMID- 17208387
TI  - Active breathing control for Hodgkin's disease in childhood and adolescence:
      feasibility, advantages, and limits.
AB  - PURPOSE: The challenge in early Hodgkin's disease (HD) in children is to maintain
      good survival rates while sparing organs at risk. This study assesses the
      feasibility of active breathing control (ABC) in children, and compares normal
      tissue irradiation with and without ABC. METHODS AND MATERIALS: Between May 2003
      and June 2004, seven children with HD with mediastinal involvement, median age
      15, were treated by chemotherapy and involved-field radiation therapy. A free
      breathing computed tomography simulation scan and one additional scan during deep
      inspiration using ABC were performed. A comparison between planning treatment
      with clinical target volume including supraclavicular regions, mediastinum, and
      hila was performed, both in free breathing and using ABC. RESULTS: For a
      prescription of 36 Gy, pulmonary dose-volume histograms revealed a mean reduction
      in lung volume irradiated at more than 20 Gy (V20) and 30 Gy (V30) of 25% and
      26%, respectively, using ABC (p = 0.016). The mean volume of heart irradiated at
      30 Gy or more decreased from 15% to 12% (nonsignificant). The mean dose delivered
      to breasts in girls was small in both situations (less than 2 Gy) and stable with
      or without ABC. Considering axillary irradiation, the mean dose delivered to
      breasts remained low (<9 Gy), without significant difference using ABC or not.
      The mean radiation dose delivered to thyroid was stable using ABC or not.
      CONCLUSIONS: Using ABC is feasible in childhood. The use of ABC decreases normal
      lung tissue irradiation. Concerning heart irradiation, a minimal gain is also
      shown. No significant change has been demonstrated concerning breast and thyroid
      irradiation.

PMID- 17208388
TI  - Intensity-modulated radiotherapy (IMRT) and conventional three-dimensional
      conformal radiotherapy for high-grade gliomas: does IMRT increase the integral
      dose to normal brain?
AB  - PURPOSE: To determine whether intensity-modulated radiotherapy (IMRT) treatment
      increases the total integral dose of nontarget tissue relative to the
      conventional three-dimensional conformal radiotherapy (3D-CRT) technique for high
      grade gliomas. METHODS AND MATERIALS: Twenty patients treated with 3D-CRT for
      glioblastoma multiforme were selected for a comparative dosimetric evaluation
      with IMRT. Original target volumes, organs at risk (OAR), and dose-volume
      constraints were used for replanning with IMRT. Predicted isodose distributions,
      cumulative dose-volume histograms of target volumes and OAR, normal tissue
      integral dose, target coverage, dose conformity, and normal tissue sparing with
      3D-CRT and IMRT planning were compared. Statistical analyses were performed to
      determine differences. RESULTS: In all 20 patients, IMRT maintained equivalent
      target coverage, improved target conformity (conformity index [CI] 95% 1.52 vs.
      1.38, p < 0.001), and enabled dose reductions of normal tissues, including
      brainstem (D(mean) by 19.8% and D(max) by 10.7%), optic chiasm (D(mean) by 25.3%
      and D(max) by 22.6%), right optic nerve (D(mean) by 37.3% and D(max) by 28.5%),
      and left optic nerve (D(mean) by 40.6% and D(max) by 36.7%), p < or = 0.01. This
      was achieved without increasing the total nontarget integral dose by greater than
      0.5%. Overall, total integral dose was reduced by 7-10% with IMRT, p < 0.001,
      without significantly increasing the 0.5-5 Gy low-dose volume. CONCLUSIONS: These
      results indicate that IMRT treatment for high-grade gliomas allows for improved
      target conformity, better critical tissue sparing, and importantly does so
      without increasing integral dose and the volume of normal tissue exposed to low
      doses of radiation.

PMID- 17208389
TI  - Management of locally recurrent soft-tissue sarcoma after prior surgery and
      radiation therapy.
AB  - PURPOSE: The aim of this study was to evaluate outcome and treatment toxicity
      after wide local re-excision (WLE), with or without additional radiation therapy,
      for patients with isolated first local recurrence of soft-tissue sarcoma arising
      within a previously irradiated field. METHODS: A retrospective review was
      performed of 62 consecutive patients. All patients underwent prior resection and
      external beam radiation. For recurrent disease, 25 patients were treated with WLE
      alone, and 37 patients were treated with WLE and additional radiation (45- 64
      Gy). In 33 patients, the radiation was delivered via an afterloaded
      brachytherapy, single-plane implant. RESULTS: The 5-year disease specific and
      distant metastasis-free survival rates were 65% and 73%, respectively. Local
      control (LC) at 5 years was 51%, and on multivariate analysis, a positive
      surgical resection margin (p< 0.001) was associated with a lower rate of LC.
      Reirradiation was not associated with improved LC; however complications
      requiring outpatient or surgical management were more common in patients who had
      undergone reirradiation (80% vs. 17%, p < 0.001). Amputation was also more common
      in the subgroup of patients who underwent extremity reirradiation (35% with
      radiation vs. 11% without, p = 0.05), although only one amputation was performed
      to resolve a treatment complication. CONCLUSION: Conservative surgery alone
      results in LC in a minority of patients who have failed locally after previous
      excision and external beam radiation. Although selection biases and small patient
      numbers confound the analysis, local treatment intensification with additional
      radiation does not clearly improve outcome after surgical excision alone, and is
      associated with an increase in complications.

PMID- 17208390
TI  - Ty1 transposition induced by carcinogens in Saccharomyces cerevisiae yeast
      depends on mitochondrial function.
AB  - The transposition of the Ty mobile genetic element of Saccharomyces cerevisiae is
      induced by carcinogens. While the molecular background of spontaneous Ty1
      transposition is well understood, the detailed mechanism of carcinogen induced
      Ty1 transposition is not clear. We found that mitochondrial functions participate
      in the Ty induced transposition induced by carcinogens. Contrary to the parental
      rho(+) cells rho(-) mutants (spontaneous or induced by ethidium bromide) do not
      increase the rate of Ty1 transposition upon treatment with carcinogens.
      Preliminary results strongly suggest that the absence of oxidative
      phosphorylation in rho(-) mutants is the reason for the inhibited Ty
      transposition. The lack of carcinogen induced Ty1 transposition in rho(-) cells
      is not specific for a particular carcinogen and represents a general feature of
      different carcinogenic substances inducing rho(-). It is concluded that
      carcinogen induced Ty1 transposition depends on the functional state of
      mitochondria and cannot take place in cells with compromised mitochondrial
      function (rho(-)).

PMID- 17208391
TI  - Expression and diversity of Echinococcus multilocularis AgB genes in secondarily
      infected mice: evaluating the influence of T-cell immune selection on antigenic
      variation.
AB  - The T-cell-mediated immune response exhibits a crucial function in the control of
      the intrahepatic proliferation of Echinococcus multilocularis larvae in mice and
      humans, both being natural intermediate hosts of the parasite. Antigen B (AgB), a
      metabolized Echinococcus spp. lipoprotein, contributes to the modulation of the T
      cell immune response, and distinct sites of the corresponding AgB1, AgB3 and AgB4
      genes were shown to be under positive selection pressure. Since several AgB gene
      variants are present in a single Echinococcus metacestode, we used secondary E.
      multilocularis infections in BALB/c and in athymic nude mice (devoid of T-cell
      responses) to analyze the effect of the cellular immune response on the
      expression and diversity of EmAgB1-EmAgB4 genes. We demonstrated hereby that
      EmAgB transcripts were less abundant in nude mice during the early phase of
      infection (at one month post-infection), and that EmAgB2 is simultaneously down
      regulated when compared to the other three genes. A negative relationship exists
      between the level of transcription and diversity of EmAgB genes. Moreover, no
      excess of non-synonymous substitutions was found among the distinct EmAgB alleles
      from a single host. Together, these results pointed to the effect of purifying
      selection, which seemed to eliminate the detrimental AgB variants generated
      during the development of the metacestode within the peritoneal cavity of its
      intermediate host.

PMID- 17208392
TI  - Genotypic characterization of Staphylococcus aureus strains isolated from rabbit
      lesions.
AB  - Since staphylococcal infections are the main pathological problem in rabbit does,
      the objective of this study was to characterize epidemiologically Staphylococcus
      aureus isolates from different lesion types in rabbits. Using 3 genetic markers
      (coagulase, staphylococcal protein A and clumping factor B genes), 22 different
      genotypes were identified among 301 isolates recovered from 259 rabbit does with
      10 different kinds of chronic purulent lesions. These infected rabbits were
      obtained from 30 herds located in the Valencia province on the Spanish
      Mediterranean coast. The most frequent genotype was designated A1/II1/delta
      (coa/spa/clfB combination genotype) and represented 70.76% of the isolates.
      Although most genotypes were previously identified in other countries, novel
      types were also documented. No specificity between genotypes and nature of the
      pathologic process could be identified. After genetic comparison between strains
      from different origins, the results may suggest that rabbit, bovine and human S.
      aureus isolates are not clonally related, suggesting that specific host-dependent
      pathogenic factors may have evolved independently in these species. These
      differences indicate that a rational and effective strategy to control infections
      caused by rabbit-specific isolates may be advantageous.

PMID- 17208393
TI  - Detection of respiratory herpesviruses in foals and adult horses determined by
      nested multiplex PCR.
AB  - A nested multiplex PCR was developed as a rapid (<12h), sensitive test for the
      simultaneous identification of equine herpesviruses (EHV1, EHV4, EHV2 and EHV5)
      in clinical samples from horses. Peripheral blood and nasal swab (NS) samples
      from 205 weanling Thoroughbred foals on 6 different studs over 3 consecutive
      seasons and from 92 adult horses without clinical signs of respiratory disease
      were examined using direct multiplex PCR of clinical samples (direct PCR) and
      conventional cell culture with differentiation of EHV in cell cultures by
      multiplex PCR. Multiplex PCR proved a sensitive and specific technique for the
      detection of EHV in cell culture and clinical samples. The technique described
      appeared equally sensitive as one using a single set of primers for individual
      EHV but reduced labour and reagent costs. Cell cultures showing cytopathic effect
      (CPE) were always positive for EHV on PCR. EHV were also detected by multiplex
      PCR in 11 samples which failed to show CPE. By a combination of multiplex PCR and
      cell culture or direct multiplex PCR, the presence of up to three EHV in the same
      sample was detected. Overall, EHV5 was detected by direct multiplex PCR of
      peripheral blood mononuclear cells (PBMC) and/or NS samples from 78% of foals and
      47% of adult horses. Repeated sampling or cell culture in combination with
      multiplex PCR and with the incorporation of IL-2 in culture medium increased the
      sensitivity for detection of EHV in PBMC and demonstrated that EHV5 DNA could be
      identified in PBMC from 89% of foals and 100% of adult horses. EHV2 was
      identified from approximately 30% of foals, but was more frequently identified in
      samples from 17 foals with mild respiratory disease and was isolated infrequently
      from adult horses. EHV1 and EHV4 were identified uncommonly in any population in
      the current study.

PMID- 17208394
TI  - Age-prevalence of Otarine Herpesvirus-1, a tumor-associated virus, and
      possibility of its sexual transmission in California sea lions.
AB  - Otarine Herpesvirus-1 (OtHV-1) is a gammaherpesvirus routinely detected in
      urogenital tumor tissues of adult sea lions dying during rehabilitation, To
      investigate the epidemiology of this virus and guide the development of a
      mathematical model of its role in the multifactorial etiology of cancer in
      California sea lions, polymerase chain reaction (PCR) amplification of an OtHV-1
      specific fragment of the DNA polymerase gene was used to look for evidence of
      OtHV-1 infection in urogenital and pharyngeal swabs and peripheral blood
      mononuclear cells (PBMC) of sea lions of different ages. Samples were also
      examined from pregnant females and their late term in utero or aborted fetuses to
      investigate potential for vertical transmission. Prevalence of infection in 72
      adult females was 22%, whereas it was 46% in 52 adult males, and was
      significantly lower in 120 juvenile animals (6%). OtHV-1 DNA was most often
      detected in the lower reproductive tract of the adult animals, especially the
      males, and rarely in the pharynx or urogenital tract of juvenile animals. These
      data suggest sexual transmission may an important route of transmission.
      Additional studies are required to confirm this mode of transmission.
      Additionally, the virus was detected in a single prematurely born pup, suggesting
      the possibility of perinatal transmission. No indication of a PBMC associated
      viremia was evident in adults using standard PCR or in juveniles using standard
      and real time PCR.

PMID- 17208395
TI  - Assessment of in vitro sperm characteristics in relation to fertility in dairy
      bulls.
AB  - The performance of frozen-thawed spermatozoa from 10 Holstein bulls in a range of
      in vitro diagnostic tests and the relationship with adjusted in vivo fertility
      data was determined. The tests included an assessment of motility (subjective and
      computer-assisted), morphology, concentration, viability, acrosomal and chromatin
      integrity conducted immediately post-thaw and after swim-up, in conjunction with
      membrane status (CTC staining) and migration in an artificial cervical mucus.
      Adjusted in vivo fertility correlated with subjectively assessed post-thaw
      motility (r=0.672, p=0.033), post-thaw straight-line velocity (r=0.636, p=0.048),
      post-thaw sperm morphology (r=-0.762, p=0.010), post-thaw sperm viability
      (r=0.635, p=0.048), the concentration of spermatozoa after swim-up (r=0.649,
      p=0.042), sperm morphology after swim-up (r=-0.687, p=0.028), the number of
      spermatozoa migrating 10mm into artificial cervical mucus (r=0.632, p=0.050) and
      the distance migrated by the vanguard spermatozoon in artificial mucus (r=0.701,
      p=0.024). A stepwise regression analysis identified tests which, when combined,
      produced models with a strong correlation (R(2)>0.9) to fertility.

PMID- 17208396
TI  - Ram effect: adult rams induce a greater reproductive response in anestrous ewes
      than yearling rams.
AB  - The introduction of rams to previously isolated anestrous ewes ensures induction
      of ovulation and estrus in part of the flock, and allows for the potential to
      conceive. However, there is little known about the desirable characteristics of
      the rams used to induce these behavioral and physiological responses. Adult rams
      may be more effective than young rams in induction of these responses. The
      primary aim of the present study was to compare the response in ewes stimulated
      by adult or yearling rams. During the non-breeding season, two groups of 121 ewes
      were stimulated with adult (AR) or yearling (YR) rams. When adult rams were used,
      significantly more ewes had ovulations (78.5 compared with 61.1%) and came into
      estrus (47.9 compared with 35.5%). There were more corpora lutea per ewe exposed
      to rams (0.95+/-0.59 compared with 0.65+/-0.51) and per ewe that had ovulations
      (1.18+/-0.41 compared with 1.06+/-0.25) and a greater conception rate (58.6
      compared with 20.9%) as a result. Subsequently, to determine what signals led to
      the greater response to adult rams, the courtship behavior of adult and yearling
      rams toward anestrous ewes was compared in 46 pen tests. There were no
      significant differences in the frequency of any of the recorded courtship
      behaviors (anogenital sniffing: 21.9+/-3.4 versus 25.7+/-3.2; lateral approaches:
      7.1+/-1.5 compared with 9.9+/-2.9; flehmen: 2.1+/-0.4 compared with 2.2+/-0.4;
      mount attempts: 0.1+/-0.1 compared with 0.1+/-0.1, for AR and YR, respectively),
      latency to the onset of courtship behavior (13.1+/-7.0 compared with 17.3+/-6.2s)
      or the time engaged in courtship behavior (173.1+/-24.6 compared with 199.0+/
      26.5s). The difference in the signals produced by adult and yearling rams skin
      glands was assessed by stimulating ewes with masks containing wool from adult
      (n=45) or yearling (n=48) rams. More ewes had ovulations (24/45 compared with
      11/48) and came into estrus (21/45 compared with 10/48) when wool from adult rams
      was used. As in Experiment 1, pregnancy and conception rates were greater when
      adult rams were used, another trial was designed to determine if there were
      differences in mating and mounting frequency between adult and yearling rams.
      Seven adult and six yearling rams were subjected to three pen tests each with
      three estrual ewes. Adult rams mounted more (21.7+/-4.5 compared with 9.8+/-0.7)
      and tended to ejaculate more frequently (2.9+/-0.5 compared with 1.8+/-0.4) than
      yearling rams. It is concluded that adult rams induce a greater reproductive
      response in anestrous ewes than yearling rams, inducing a greater ovulation
      percentage and estrous response in ewes, resulting in greater ovulation numbers,
      pregnancy and conception rates. This greater stimulation is, in part, explained
      by differences in the signals provided in the wool (presumably odors) produced by
      adult rams. The lesser percentage of pregnancies obtained when yearling rams are
      used may be explained by differences in mounting behaviors and ejaculation
      frequency.

PMID- 17208397
TI  - Neural and behavioral correlates of auditory categorization.
AB  - Goal-directed behavior is the essence of adaptation because it allows humans and
      other animals to respond dynamically to different environmental scenarios. Goal
      directed behavior can be characterized as the formation of dynamic links between
      stimuli and actions. One important attribute of goal-directed behavior is that
      linkages can be formed based on how a stimulus is categorized. That is, links are
      formed based on the membership of a stimulus in a particular functional category.
      In this review, we review categorization with an emphasis on auditory
      categorization. We focus on the role of categorization in language and non-human
      vocalizations. We present behavioral data indicating that non-human primates
      categorize and respond to vocalizations based on differences in their putative
      meaning and not differences in their acoustics. Finally, we present evidence
      suggesting that the ventrolateral prefrontal cortex plays an important role in
      processing auditory objects and has a specific role in the representation of
      auditory categories.

PMID- 17208398
TI  - 3p-- syndrome defines a hearing loss locus in 3p25.3.
AB  - Deletions affecting the terminal end of chromosome 3p result in a characteristic
      set of clinical features termed 3p-- syndrome. Bilateral, sensorineural hearing
      loss (SNHL) has been found in some but not all cases, suggesting the possibility
      that it is due to loss of a critical gene in band 3p25. To date, no genetic locus
      in this region has been shown to cause human hearing loss. However, the ATP2B2
      gene is located in 3p25.3, and haploinsufficiency of the mouse homolog results in
      SNHL with similar severity. We compared auditory test results with fine deletion
      mapping in seven previously unreported 3p-- syndrome patients and identified a
      1.38Mb region in 3p25.3 in which deletions were associated with moderate to
      severe, bilateral SNHL. This novel hearing loss locus contains 18 genes,
      including ATP2B2. ATP2B2 encodes the plasma membrane calcium pump PMCA2. We used
      immunohistochemistry in human cochlear sections to show that PMCA2 is located in
      the stereocilia of hair cells, suggesting its function in the auditory system is
      conserved between humans and mice. Although other genes in this region remain
      candidates, we conclude that haploinsufficiency of ATP2B2 is the most likely
      cause of SNHL in 3p-- syndrome.

PMID- 17208400
TI  - Hair analysis for diphenhydramine after surreptitious administration to a child.
AB  - Diphenhydramine is one of the first effective antihistamine agents to have been
      discovered. The compound is also used for its sedative and antiemetic effects.
      The first case involving repetitive sedation linked to the use of diphenhydramine
      as a drug-facilitated crime and subsequent impairment of a 9-year-old female
      victim is reported. Due to the long delay between the alleged crime and clinical
      examination, collection of blood or urine was of little value. Hence, the
      laboratory developed an original approach based on hair testing by LC-MS/MS. A
      single strand of hair from the victim was sampled about 7 weeks after the last
      suspected administration and was cut into small segments. After cutting into
      small pieces, about 20 mg of hair per segment was incubated overnight in a
      phosphate buffer (pH 8.4). The aqueous phase was extracted with 5 ml of a mixture
      of methylene chloride/diethyl ether (80/20), in presence of diazepam-d5, used as
      internal standard (IS). The hair extract was separated on an XTerra MS C18 column
      using a gradient of acetonitrile and formate buffer. Detection was based on two
      daughter ions: transitions m/z 256.2-152.1 and 167.1 and m/z 289.9-154.0 for
      diphenhydramine and the IS, respectively. In the hair of the child,
      diphenhydramine was detected at concentrations in the range 33-39 pg/mg,
      depending on the segment.

PMID- 17208399
TI  - An immunohistochemical study in a fatal case of acute interstitial pneumonitis
      (Hamman-Rich syndrome) in a 15-year-old boy presenting as sudden death.
AB  - Acute interstitial pneumonitis (AIP), also known as Hamman-Rich syndrome, is a
      distinct type of idiopathic interstitial pneumonia affecting patients of both
      genders without pre-existing lung diseases. We describe the case of a fulminant
      form of AIP and discuss the pathophysiological mechanisms of AIP with reference
      to the histological pattern. A 15-year-previously-healthy male boy presented to
      the Hospital with a 6-day history of malaise, fever and cough. The clinical
      prodromes were followed by the acute onset of increasing shortness of breath
      rapidly progressing in acute respiratory failure. Chest X-ray demonstrated
      bilateral diffuse airspace opacification; the high resolution CT confirmed the
      presence of bilateral, symmetric diffuse ground-glass attenuation. The patient
      was admitted to the intensive care unit, but died after few hours. An autopsy was
      performed within 24h. The histological examination of lung specimens showed a
      pattern of diffuse alveolar damage. immunohistochemical, microbiological and
      toxicological tests were also carried out. The clinical presentation, the
      histological findings and the exclusion of infective, traumatic, toxic and
      metabolic causes of acute respiratory distress syndrome (ARDS) allowed us to
      conclude that the boy was affected by AIP. In conclusion, AIP is a diagnosis of
      exclusion. It has a mortality rate ranging about 50%, despite mechanical
      ventilation. In fatal cases of AIP diagnosis can be based on clinical
      presentation, radiological, histological and microbiological findings and can be
      further confirmed by immunohistochemical analysis.

PMID- 17208401
TI  - Signaling lymphocyte activating molecule (SLAM) expression in subacute sclerosing
      panencephalitis.
AB  - Signaling lymphocyte activating molecule (SLAM) is a receptor for measles virus
      which also has immunomodulatory activity. We analyzed SLAM expression in
      mononuclear cells (MNC) of patients with SSPE (n=7) and control subjects (n=7)
      from the same population. Native 10% PAGE analysis in cell and brain tissue
      extracts followed by Western blotting using monoclonal anti-human SLAM showed
      four types of bands. Differences in the type and amount of SLAM expression were
      observed between SSPE and control cases. Lymphocytes of SSPE patients showed two
      types of SLAM bands in comparison to only one in control lymphocytes. Stimulation
      of cells with lipopolysaccharide (80 u/ml) and concanavalin A (1 microg/ml) in
      vitro led to the appearance of a second isoform in both groups. Brain homogenates
      of SSPE patients (n=2) displayed all four types of SLAM isoforms at significantly
      higher levels than those of control brains (n=2). Our results show native PAGE
      enables the detection of all SLAM isotypes. The expression of SLAM is increased
      in lymphocytes, monocytes, and brain tissues of SSPE patients.

PMID- 17208402
TI  - The phylogeny of the genus Nitrobacter based on comparative rep-PCR, 16S rRNA and
      nitrite oxidoreductase gene sequence analysis.
AB  - Strains of Nitrobacter mediate the second step in the nitrification process by
      oxidizing nitrite to nitrate. The phylogenetic diversity of the genus is
      currently not well investigated. In this study, a rep-PCR profile and the nearly
      complete 16S rRNA gene sequence of 30 strains, comprising a wide physiological as
      well as ecological diversity and encompassing representatives of the four
      species, were determined. The sequence diversity of the 16S rRNA gene between
      different species was low, indicating the need for additional phylogenetic
      markers. Therefore, primers were developed for amplifying the complete nxrX gene
      and a 380bp fragment of the nxrB1 gene, which are both genes involved in the
      nitrite oxidation process. These genes confirmed the division into phylogenetic
      groups revealed by the 16S rRNA gene but showed a better discriminatory power.
      They can be a valuable additional tool for phylogenetic analysis within the genus
      Nitrobacter and can assist in the identification of new Nitrobacter isolates.

PMID- 17208403
TI  - Multi-criteria decision making approach and experimental design as chemometric
      tools to optimize HPLC separation of domperidone and pantoprazole.
AB  - This paper deals with multiple response simultaneous optimization using the
      Derringer's desirability function for the development of a reversed-phase HPLC
      method for the simultaneous determination of domperidone and pantoprazole in
      commercial pharmaceutical preparations. Twenty experiments, taking the retention
      factor of the first peak, the two resolutions, and three retention times as the
      responses with three important factors, mobile phase composition, buffer molarity
      and flow rate, were used to design mathematical models. The experimental
      responses were fitted into a second order polynomial and the six responses
      simultaneously optimized to predict the optimum conditions for the effective
      separation of the studied compounds. The optimum assay conditions were: methanol
      acetonitrile-dipotassium hydrogen phosphate (pH 7.0; 15.3 mM) (20:33:47, v/v/v)
      as the mobile phase and at a flow rate of 1.19 ml/min. While using this optimum
      condition, baseline separation with a minimum resolution of 2.0 and a run time of
      less than 6 min were achieved. The method showed good agreement between the
      experimental data and predictive value throughout the studied parameter space.
      The optimized assay condition was validated according to ICH guidelines to
      confirm specificity, linearity, accuracy and precision.

PMID- 17208404
TI  - LC/ESI-MS method for the determination of trimetazidine in human plasma:
      application to a bioequivalence study on Chinese volunteers.
AB  - A rapid liquid chromatography electrospray ionization mass spectrometry (LC/ESI
      MS) method with good sensitivity and specificity has been developed and validated
      for the identification and quantification of trimetazidine in human plasma.
      Trimetazidine and lidocaine (internal standard) were isolated from plasma samples
      by protein precipitation with methanol. The chromatographic separation was
      accomplished on a Xterra MS C18 Column (150 mm x 4.6 mm, 5 microm particle size)
      with the mobile phase consisting of methanol and water (40:60, v/v) (pH 2.0,
      adjusted with trifluoroacetic acid), and the flow rate was set at 0.6 mL/min.
      Detection was performed on a single quadruple mass spectrometer by selected ion
      monitoring (SIM) mode (m/z 267.0 for trimetazidine and m/z 235.0 for lidocaine)
      with the retention time at about 3.47 and 5.05 min, respectively. The calibration
      curve for trimetazidine was satisfactory with regression coefficient 0.9995 over
      the range of 2.5-100 ng/mL in the plasma. The LOQ (S/N=10) was accordingly 2.5
      ng/mL. The intra-day and inter-day precision expressed as relative standard
      deviation was 2.83-6.10% and 4.83-5.82%. The method was successfully applied to
      investigate the bioequivalence between two kinds of tablets (test versus
      reference product) in 19 healthy male Chinese volunteers. After a single 20 mg
      dose for the test and reference product, the resulting mean of major
      pharmacokinetic parameters such as AUC(0-24), AUC(0-infinity), Cmax, Tmax and
      t(1/2) of trimetazidine were (673.1+/-117.6 ng h mL(-1) versus 652.3+/-121.9 ng h
      mL(-1)), (717.1+/-120.9 ng h mL(-1) versus 692+/-128.6 ng h mL(-1)), (74.85+/
      12.13 ng mL(-1) versus 71.93+/-14.32 ng mL(-1)), (2.312+/-0.663 h versus 2.211+/
      0.608 h) and (4.785+/-0.919 h versus 4.740+/-0.823 h), respectively, indicating
      that these two kinds of tablets were bioequivalent in the Chinese population.

PMID- 17208405
TI  - Ochratoxin A in nephropathic patients from two cities of central zone in
      Portugal.
AB  - Ochratoxin A (OTA) produced by Aspergillus and Penicillium genera contaminates
      several foods. 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 examined species. OTA has other toxic effects such as teratogenicity,
      immunotoxicity, genotoxicity, and is also mutagenic and carcinogenic, all of
      which lead to life-threatening pathologies through several molecular pathways. A
      sensitive, specific and rapid method applying high performance liquid
      chromatography coupled to a spectrofluorimeter for the determination of
      ochratoxin A in human serum was validated. Serum samples were extracted with
      chloroform-orthophosphoric acid, and cleaned-up through immunoaffinity column
      (IAC). The separation and identification was performed by HPLC coupled to a
      spectrofluorimeter, and, after OTA methylation, the confirmation was achieved.
      Chromatographic separation of the analyte was performed on a reverse phase column
      with a mobile phase of water:acetonitrile:glacial acetic acid (49.5:49.5:1.0).
      Linearity was established between the range of 1 and 10 ng/ml. Under the
      optimized conditions, the recoveries were higher than 83.0% for all fortification
      levels. The intra-day precision oscillated between 8.0 and 5.0% at levels of 0.25
      and 0.5 microg/l, while the inter-day precision was in the range of 10.7-16.0%.
      The limit of quantification of the method was 0.05 microg/l. The method is
      appropriate for quantitative determination of OTA in human serum and has been
      successfully applied to the analysis of OTA in haemodialysis patients from two
      principal cities of Portugal, in order to evaluate its exposure degree. Levels of
      OTA in Coimbra were higher than in Aveiro, 0.50 microg/l versus 0.49 microg/l. In
      respect to gender, levels of OTA were higher in males from Aveiro than in
      females, 0.52 microg/l versus 0.44 microg/l, and in Coimbra were similar, 0.50
      microg/l versus 0.51 microg/l. However, in none of the cases, significant
      statistical differences were found.

PMID- 17208406
TI  - Biotechnological significance of toxic marine dinoflagellates.
AB  - Dinoflagellates are microalgae that are associated with the production of many
      marine toxins. These toxins poison fish, other wildlife and humans.
      Dinoflagellate-associated human poisonings include paralytic shellfish poisoning,
      diarrhetic shellfish poisoning, neurotoxic shellfish poisoning, and ciguatera
      fish poisoning. Dinoflagellate toxins and bioactives are of increasing interest
      because of their commercial impact, influence on safety of seafood, and potential
      medical and other applications. This review discusses biotechnological methods of
      identifying toxic dinoflagellates and detecting their toxins. Potential
      applications of the toxins are discussed. A lack of sufficient quantities of
      toxins for investigational purposes remains a significant limitation. Producing
      quantities of dinoflagellate bioactives requires an ability to mass culture them.
      Considerations relating to bioreactor culture of generally fragile and slow
      growing dinoflagellates are discussed. Production and processing of
      dinoflagellates to extract bioactives, require attention to biosafety
      considerations as outlined in this review.

PMID- 17208407
TI  - Radical vaginal trachelectomy (Dargent's operation): a critical review of the
      literature.
AB  - AIMS: To present a review of the most recent articles about radical vaginal
      trachelectomy (RVT). METHODS: Recent literature has been reviewed, concentrating
      on surgical, oncological and obstetrical outcome of RVT. Data for this review
      were identified by searches of PubMed, and references from relevant articles
      using the search terms "trachelectomy" and "radical vaginal trachelectomy",
      "cervical carcinoma", and "fertility saving". FINDINGS: Although a considerable
      number of women in their reproductive years have been diagnosed with cervical
      carcinoma, conservative management of early-stage cervical carcinoma did not come
      into practice until the beginning of the new millennium. To date, 7 gynecologic
      oncologic centers worldwide have reported oncological and pregnancy outcomes
      since Dargent made his first announcement of radical vaginal trachelectomy (RVT)
      in 1994. Recurrence and death rates (4.2% and 2.8%, respectively) of RVT seem to
      be comparable to classical radical abdominal hysterectomy. It appears that RVT's
      overall recurrence and death rates were similar to early-stage cervical cancer
      treated by radical hysterectomy (RH) or radiotherapy. Furthermore fertility
      results of RVT seem to be promising. A 70% pregnancy rate was reported in the
      women who wanted to conceive following RVT, though such patients should be
      informed about the risk of second trimester loss and preterm delivery. On the
      other hand, there is a lack of satisfactory information about the follow-up of
      post-RVT patients, both after the operation and during subsequent pregnancy.
      CONCLUSION: RVT looks as if it is a valid uterus-conserving surgery for women of
      reproductive age who have early-stage cervical carcinoma. However, in order to
      reach a final conclusion about the oncological and obstetrical results, further
      studies are needed with larger sample sizes and longer follow-up periods.

PMID- 17208408
TI  - Promoter profiling and coexpression data analysis identifies 24 novel genes that
      are coregulated with AMPA receptor genes, GRIAs.
AB  - We identified a set of transcriptional elements that are conserved and
      overrepresented within the promoters of human, mouse, and rat GRIAs by comparing
      these promoters against a collection of 10,741 gene promoters. Cells regulate
      functional groups of genes by coordinating the transcriptional and/or
      posttranscriptional mRNA levels of interacting genes. As such, it is expected
      that functional groups of genes share the same transcriptional features within
      their promoters. We found 47 genes whose promoters contain the same combination
      of transcriptional elements that are overrepresented within the promoters of the
      GRIA gene family. Coexpressed genes may be transcriptionally coregulated, which
      in turn suggests that these genes may play complementary roles within a
      particular functional context. Using microarray expression data, we found 24 (of
      the 47) genes that share not only a similar promoter profile with GRIAs but also
      a well-correlated gene expression profile and, thus, we believe these to be
      coregulated with GRIAs.

PMID- 17208409
TI  - The use of a new 3D splint and double CT scan procedure to obtain an accurate
      anatomic virtual augmented model of the skull.
AB  - Three-dimensional (3D) virtual planning of orthognathic surgery requires detailed
      visualization of the interocclusal relationship. The purpose of this study was to
      introduce the modification of the double computed tomography (CT) scan procedure
      using a newly designed 3D splint in order to obtain a detailed anatomic 3D
      virtual augmented model of the skull. A total of 10 dry adult human cadaver
      skulls were used to evaluate the accuracy of the automatic rigid registration
      method for fusion of both CT datasets (Maxilim, version 1.3.0). The overall mean
      registration error was 0.1355+/-0.0323 mm (range 0.0760-0.1782 mm). Analysis of
      variance showed a registration method error of 0.0564 mm (P < 0.001; 95%
      confidence interval = 0.0491-0.0622). The combination of the newly designed 3D
      splint with the double CT scan procedure allowed accurate registration and the
      set-up of an accurate anatomic 3D virtual augmented model of the skull with
      detailed dental surface.

PMID- 17208410
TI  - Distinct absorption characteristics of oral formulations of valproic
      acid/divalproex available in the United States.
AB  - Five oral formulations of valproic acid (VPA)/divalproex sodium are approved and
      commonly used in the US for treatment of epilepsy, mania/bipolar disorder and
      migraine prophylaxis. These formulations have unique pharmacokinetic and
      formulation characteristics and are designed to treat distinct patient
      populations. We compared the absorption characteristics of all five oral
      VPA/divalproex formulations currently available in the US. Plasma VPA
      concentration-time profiles, following single oral dose (250mg) administration of
      five VPA/divalproex formulations under fasting conditions, from three
      pharmacokinetic studies in healthy subjects (N=9-15 each) were compared. The five
      VPA/divalproex formulations demonstrated marked absorption differences. The rate
      of absorption, as characterized by maximum concentration (C(max)) and time to
      C(max) (T(max)), may be rank-ordered as: VPA syrup (34.2mg/L, 0.9h)>VPA capsule
      (31.4mg/L, 2.2h)>divalproex sodium sprinkle capsule (20.7mg/L, 4.0h; lag-time
      congruent with1h) congruent withdivalproex sodium enteric-coated delayed-release
      tablet (26.0mg/L, 3.4h; lag-time congruent with2h)>divalproex sodium extended
      release (divalproex-ER) tablet (11.8mg/L, 19.7h). Divalproex-ER had approximately
      11% lower exposure (AUC). The comparable AUC across the five formulations, when
      corrected for bioavailability differences, demonstrates that formulation
      primarily affects the drug-release and in vivo absorption of VPA. Only divalproex
      ER demonstrated true sustained-release characteristics.

PMID- 17208411
TI  - Phenylthiocarbamide (PTC) perception in patients with schizophrenia and first
      degree family members: relationship to clinical symptomatology and psychophysical
      olfactory performance.
AB  - The inability to taste phenylthiocarbamide (PTC; "taste-blindness") has been
      associated with a number of medical and neurological illnesses not typically
      related to taste. We examined PTC sensitivity in 67 schizophrenia patients, 30
      healthy controls, and 30 first-degree relatives to determine whether taster
      status could represent a simple vulnerability marker. A higher prevalence of non
      tasters was seen in patients and family members relative to healthy controls.
      Among patients, non-tasters exhibited increased levels of negative and first-rank
      symptoms as well as poorer right nostril odor identification skills relative to
      PTC tasters. These differences were not explained by age, sex, education,
      smoking, or intensity differences. Phenotypic variation in PTC sensitivity is
      thought to be genetic in origin and suggests greater illness risk for those
      subjects with recessive taster alleles.

PMID- 17208412
TI  - The effects of antipsychotic drugs on GABAA receptor binding depend on period of
      drug treatment and binding site examined.
AB  - Changes in GABA(A) receptors are observed in schizophrenia, with benzodiazepine
      sensitive GABA(A) receptor subtypes being affected differently to other subtypes.
      However, long-term antipsychotic drug use in schizophrenia may underlie these
      changes. To test this, we examined the effects of administering a typical
      (haloperidol) and an atypical (olanzapine) antipsychotic drug on the GABA(A)
      receptor agonist (orthosteric) and benzodiazepine (allosteric) binding sites in
      rat prefrontal cortex. As antipsychotic drugs have delayed maximal therapeutic
      effects we also examined different drug treatment periods. Male SD rats received
      a sucrose solution containing either haloperidol (1.5 mg/kg), olanzapine (6.5
      mg/kg) or no drug daily for either 7, 14 or 28 days. Sections of rat brain were
      then labelled with [(3)H]muscimol, which labels the total population of GABA(A)
      receptors, or the benzodiazepine site ligand [(3)H]flunitrazepam in separate
      saturation binding experiments using quantitative receptor autoradiography.
      [(3)H]Muscimol binding was enhanced in the prefrontal cortex after 7 days but no
      differences were observed after longer periods of drug administration. In
      contrast there was a delayed increase in density of benzodiazepine-sensitive
      GABA(A) receptors in the PFC, suggesting that antipsychotic drugs have different
      effects on different GABA(A) receptor subtypes. These changes in the properties
      of GABA(A) receptor binding following antipsychotic drug administration are not
      consistent with those observed in schizophrenia and suggest a 'reshuffling' in
      GABA(A) receptor subtypes over time.

PMID- 17208413
TI  - Celecoxib as adjunctive therapy in schizophrenia: a double-blind, randomized and
      placebo-controlled trial.
AB  - Some evidence suggests that the pathophysiology of schizophrenia is associated
      with the abnormal immune system, and cytokines may be important in schizophrenia.
      Cyclooxygenase-2 (COX-2) inhibitors such as celecoxib reduce the production of
      proinflammatory cytokines including Th1-like cytokines. Indeed, COX-2 inhibitors
      rebalance type-1 and type-2 immune response. The purpose of the present
      investigation was to assess the efficacy of celecoxib as an adjuvant agent in the
      treatment of chronic schizophrenia in an eight-week, double-blind and placebo
      controlled trial. Eligible participants in this study were 60 patients with
      chronic schizophrenia. All patients were inpatients and were in the active phase
      of the illness, and met DSM-IV criteria for schizophrenia. Patients were
      allocated in a random fashion, 30 to risperidone 6 mg/day plus celecoxib 400
      mg/day (200 mg bid) (morning and evening) and 30 to risperidone 6 mg/day plus
      placebo. Although both protocols significantly decreased the score of the
      positive, negative and general psychopathological symptoms over the trial period,
      the combination of risperidone and celecoxib showed a significant superiority
      over risperidone alone in the treatment of positive symptoms, general
      psychopathology symptoms as well as PANSS total scores. The means Extrapyramidal
      Symptoms Rating Scale for the placebo group were higher than in the celecoxib
      group over the trial. However, the differences were not significant. The results
      of this study suggest that celecoxib may be an effective adjuvant agent in the
      management of patients with chronic schizophrenia and anti-inflammatory therapies
      should be further investigated.

PMID- 17208414
TI  - The use of electronic monitoring (MEMS) to evaluate antipsychotic compliance in
      outpatients with schizophrenia.
AB  - Compliance with antipsychotic treatment is a well-recognized concern in the
      ongoing management of individuals with schizophrenia. The present investigation
      incorporated the Medication Event Monitoring System (MEMS) to evaluate compliance
      in a group of outpatients (N=52) with schizophrenia or schizoaffective disorder.
      Evaluating compliance as a dichotomous variable and using a threshold of 80%, the
      rate of noncompliance as measured by MEMS was 52%, considerably higher than self
      report (3%), clinician rating (24%) and pill count (25%). The ability of treating
      clinicians to predict compliance/noncompliance was limited: 13 of 31 (42%)
      subjects they rated as compliant were noncompliant while 4 of 9 (44%) rated as
      noncompliant were actually compliant according to MEMS. Factors most consistently
      associated with noncompliance were higher total symptom scores and dosing
      complexity i.e., greater than once daily. Based on MEMS data, the overall mean
      level of compliance was 66%; however, it remains unclear as to what threshold is
      associated with a compromise in clinical response. More sophisticated measurement
      tools such as MEMS may assist us in better understanding how level and pattern of
      antipsychotic noncompliance, factors that at present remain poorly understood,
      impact on symptom exacerbation.

PMID- 17208415
TI  - Tobacco smoke extract induces premature skin aging in mouse.

PMID- 17208417
TI  - Alzheimer disease: amyloidogenesis, the presenilins and animal models.
AB  - Alzheimer's disease is the most prevalent form of dementia. Neuropathogenesis is
      proposed to be a result of the accumulation of amyloid beta peptides in the brain
      together with oxidative stress mechanisms and neuroinflammation. The presenilin
      proteins are central to the gamma-secretase cleavage of the amyloid prescursor
      protein (APP), releasing the amyloid beta peptide. Point mutations in the
      presenilin genes lead to cases of familial Alzheimer's disease by increasing APP
      cleavage resulting in excess amyloid beta formation. This review discusses the
      molecular mechanism of Alzheimer's disease with a focus on the presenilin genes.
      Alternative splicing of transcripts from these genes and how these may function
      in several disease states is discussed. There is an emphasis on the importance of
      animal models in elucidating the molecular mechanisms behind the development of
      Alzheimer's disease and how the zebrafish, Danio rerio, can be used as a model
      organism for analysis of presenilin function and Alzheimer's disease
      pathogenesis.

PMID- 17208416
TI  - Regulated ion transport in mouse liver cyst epithelial cells.
AB  - Derived from bile duct epithelia (BDE), secretion by liver cyst-lining epithelia
      is positioned to drive cyst expansion but the responsible ion flux pathways have
      not been characterized. Cyst-lining epithelia were isolated and cultured into
      high resistance monolayers to assess the ion secretory pathways.
      Electrophysiologic studies showed a marked rate of constitutive transepithelial
      ion transport, including Cl(-) secretion and Na(+) absorption. Na(+) absorption
      was amiloride-sensitive, suggesting the activation of epithelial sodium channels
      (ENaC). Further, both cAMP(i) and extracellular ATP induced robust secretory
      responses. Western blotting and immunohistologic analysis of liver cyst epithelia
      demonstrated expression of P2X4, a potent purinergic receptor in normal BDE.
      Luminometry and bioassaying measured physiologically relevant levels of ATP in a
      subset of liver cyst fluid samples. Liver cyst epithelia also displayed a
      significant capacity to degrade extracellular ATP. In conclusion, regulated ion
      transport pathways are present in liver cyst epithelia and are positioned to
      direct fluid secretion into the lumen of liver cysts and promote increases in
      liver cyst expansion and growth.

PMID- 17208418
TI  - Proton magnetic resonance spectroscopy reveals an abnormality in the anterior
      cingulate of a subgroup of obsessive-compulsive disorder patients.
AB  - Numerous neuroimaging studies have suggested that obsessive-compulsive disorder
      (OCD) patients had a neurobiological abnormality in the frontal-subcortical
      circuits. On the other hand, there are distinct differences in the responses to
      pharmacological treatment among OCD patients. In the present study, we measured
      the concentration of N-acetyl aspartate (NAA), a putative marker of neuronal
      viability, with proton magnetic resonance spectroscopy (MRS) in OCD patients with
      different pharmacological responses. Participants comprised 20 patients and 26
      healthy control subjects. OCD patients were divided into three groups according
      to the pharmacological response; responders to a selective serotonin reuptake
      inhibitor (SSRI) (group A: n=7), responders to SSRI with an atypical
      antipsychotic (group B: n=8) and non-responders to either SSRI or SSRI with an
      atypical antipsychotic (group C: n=5). Short echo proton MRS was used to measure
      NAA concentrations in the anterior cingulate, the left basal ganglia and the left
      prefrontal lobe of subjects. A significantly lower NAA concentration was observed
      only in group B compared with control subjects in the anterior cingulate. Our
      results suggest that a subgroup of OCD patients who respond to an SSRI with an
      atypical antipsychotic have distinct biological abnormalities in the anterior
      cingulate.

PMID- 17208419
TI  - Retardation of crystallization-induced destabilization of PMF-in-water emulsion
      with emulsifier additives.
AB  - An oil-in-water (O/W) emulsion, in which the oil phase is semi-solid fat, is
      easily destabilized when stored below the crystallization temperature of the oil
      phase. Such destabilization, characterized by loss of fluidity at chilled
      temperature and oil-water separation after re-heating, is caused by inter-droplet
      bridging of fat crystals protruding out of the emulsion droplets. In the present
      study, we found that the simultaneous use of additives of highly hydrophobic
      sucrose oligoester (SOE; P-170) and highly hydrophilic SOE (P-1670) containing
      palmitic acid moiety remarkably retarded the crystallization-induced
      destabilization of the O/W emulsion that contains palm-mid-fraction (PMF) as the
      oil phase. Without the additives, destabilization occurred when the emulsion was
      cooled from 60 to 0 degrees C and kept at 0 degrees C for 1 day. Microscopic
      observation revealed that destabilization was caused by coalescence of the oil
      droplets, which was triggered by the growth of needle-shaped PMF crystals
      protruding out of the emulsion membranes. However, the addition of P-170 to PMF
      increased the crystallization temperature of PMF and at the same time retarded
      the destabilization. Furthermore, the simultaneous addition of P-170 and P-1670
      retarded the crystallization-induced destabilization even more. Optical
      observation, DSC, and synchrotron radiation X-ray diffraction measurements
      indicated that the P-170 additive enhanced interfacial heterogeneous
      crystallization to form tiny PMF crystals in the droplets, and that the P-1670
      additive retarded morphological change of the PMF crystals into long needle
      shapes in association with polymorphic transformation from alpha to beta'.

PMID- 17208420
TI  - Light exposure dependence of molecular orientation of glassy polyfluorene layers
      formed on photo-aligned polyimide films.
AB  - We have investigated the molecular orientation of glassy poly(9,9
      dioctylfluorenyl-2,7-diyl) (PFO) layers formed on photo-aligned polyimide films
      with different in-plane anisotropy. The polyimide contains azobenzene in the
      backbone structure (Azo-PI), allowing us to control the in-plane anisotropy of
      the film by varying linearly polarized light (LP-L) exposure. The glassy PFO
      layers (approximately 30 nm thick) were obtained by annealing the samples at the
      liquid crystalline phase of PFO and then quenching them to room temperature. The
      degree of alignment of PFO was assessed by the polarization ratio of
      photoluminescence (PL). The PL polarization ratio increased rapidly with the LP-L
      exposure, and it reached 10 at 2.8 J/cm(2). Beyond this LP-L exposure, it became
      almost constant around 10.4. This PL polarization ratio was much higher than the
      absorption dichroic ratio of the underlying Azo-PI film. This result suggests
      that the degree of alignment of PFO is determined by its liquid crystalline
      nature. The saturation dependence of the degree of alignment is very useful for
      fabricating alignment patterns by a simple photo-mask exposure method. We have
      succeeded in fabricating 3 microm line-and-space alignment patterns of PFO.

PMID- 17208422
TI  - Binding and fluorescence study on interaction of human serum albumin (HSA) with
      cetylpyridinium chloride (CPC).
AB  - Human serum albumin (HSA) is frequently used in biophysical and biochemical
      studies since it has a well-known primary structure and it has been associated
      with the binding of many different categories of small molecules. In the present
      study, results are presented for the binding of cetylpyridinium chloride (CPC)
      with HSA at various pH and 25 degrees C, as monitored using ion selective
      membrane electrodes and fluorescence spectroscopy of intrinsic tryptophan. The
      obtained binding isotherms were analyzed on basis of binding capacity concept and
      Hill plot in order to determine the Hill parameters of binding sets. The system
      behaved as a system with two sets of binding sites in all studied situations. The
      results represent a positive cooperative behavior and the essential role of
      hydrophobic interactions in both binding sets. The intrinsic binding affinity of
      second binding set have a similar values and trends at acidic and neutral pHs,
      that represents the similar unfolded structure at these pHs. CPC quenched the
      fluorescence arising from Trp group incorporated to HSA. A biphasic behavior was
      observed in quenching process that confirmed the results of binding study
      correspond to the existence of two binding sets. The similarity of unfolded
      structure in acidic and neutral pH was also confirmed by fluorescence study. The
      quenching of HSA fluorescence takes place with a Stern-Volmer constant of 0.643 x
      10(4), 1.23 x 10(4) and 7.40 x 10(4) at pH 3.5, 6.8 and 9.5, respectively. The
      Stern-Volmer behavior observed at low molar ratio of [CPC]/[HSA] (about 6), that
      represents the occurrence of conformational changes after this molar ratio.
      Comparing, the K(SV) values and binding parameters indicate that the binding is
      dominated by hydrophobic effects and, in minor degree, by electrostatic
      interactions.

PMID- 17208421
TI  - Stable expression of foot-and-mouth disease virus protein VP1 fused with cholera
      toxin B subunit in the potato (Solanum tuberosum).
AB  - The expression vector, pBI121CTBVP1, containing the fusion of the foot and mouth
      disease virus (FMDV) VP1 gene and the cholera toxin B subunit (CTB) gene was
      constructed by fused PCR and transferred into potato (Solanum tuberosum L.) by
      Agrobacterium-mediated transformation. Transformed plants were obtained by
      selecting on kanamycin-resistant medium strictly and regenerated. The transgenic
      plantlets were identified by PCR, Southern-blot and the production of fused
      protein was confirmed and quantified by Western-blot and ELISA assays. The
      results showed that the fused genes were expressed stablely under the control of
      specific-tuber patatin promoter. The expressed fused proteins have a certain
      degree of immunogenicity.

PMID- 17208424
TI  - The fatty acid profiles in a drop of blood from a fingertip correlate with
      physiological, dietary and lifestyle parameters in volunteers.
AB  - Limited data are available on the fatty acid (FA) composition of circulating
      lipids and the associations with diet, physiological and pathological conditions,
      due to the complexity and costs of the analytical process. The aim of our study
      was to evaluate the FA composition in 108 healthy subjects and to correlate the
      data with gender, pregnancy, dietary habits, lifestyle, and short-term controlled
      intake of n-3 FA, using an innovative analytical approach for the collection and
      processing of blood samples. Ten subjects were also supplemented with n-3
      polyunsaturated FA as smoked salmon or capsules for 3 weeks. The resulting blood
      FA composition was affected by gender, pregnancy, diet and smoking. The data
      indicate that this new analytical methodology is suitable for assessing
      associations between circulating FA and various parameters in large population
      groups, and is applicable to epidemiological studies and in the assessment of the
      effects of controlled FA supplementation in clinical studies.

PMID- 17208423
TI  - [Autism and mental retardation: a study of the early social communication].
AB  - OBJECTIVE: To determine developmental communication profiles in young autistic
      children with mental retardation. METHODS: A group of 19 autistic children (mean
      age=43 months) were matched with a group of 11 mentally retarded children (mean
      age=39 months) on mental age (17,6 months). All of these children were without
      speech (less than 5 words of vocabulary). Communication skills were assessed with
      the Guidetti-Tourrette scales (ECSP), French adaptation of the Seibert-Hogan
      scales. RESULTS: Autistic children displayed a much lower score than mentally
      retarded children in the 3 functions of early social communication (behavior
      regulation, social interaction and joint attention). The developmental
      communication profiles was the same in the 2 groups. DISCUSSION: The results
      showed evidence of distortion in autistic children development: they displayed
      important deficits in communication skills, in comparison with cognitive skills.
      Autistic children mainly displayed requesting gestures: they used adults to help
      them to reach a goal, instead of regarding them as social partners. However,
      young children who have mental age less than 18 months mainly use the same
      functions of communication, with or without autistic trouble. CONCLUSIONS: There
      is a same developmental sequence in communication skills in young children, with
      or without autistic trouble.

PMID- 17208425
TI  - Regulation and recycling of myosin V.
AB  - Recently there has been considerable progress in our understanding of regulation
      for unconventional myosin-V through elucidation of the structure of its inactive
      conformation and the factors that affect stability of this conformation. The
      inactive conformation is a folded compact structure characterized by interactions
      between the myosin head and the C-terminal cargo binding domain. Concentrations
      of Ca2+ greater than 10 microM disrupt folding. The 3-D structure determined by
      cryoelectron tomography of 2-D arrays in one study and electron micrographs of
      isolated molecules reported in another reveal similar features, but suggest
      different F-actin affinities for the inactive conformation. This has raised the
      question of how inactive myosin-V is recycled to other sites for additional
      rounds of cargo transport.

PMID- 17208426
TI  - Imprinted polymer-modified hanging mercury drop electrode for differential pulse
      cathodic stripping voltammetric analysis of creatine.
AB  - The molecularly imprinted polymer [poly(p-aminobenzoicacid-co-1,2
      dichloroethane)] film casting was made on the surface of a hanging mercury drop
      electrode by drop-coating method for the selective and sensitive evaluation of
      creatine in water, blood serum and pharmaceutical samples. The molecular
      recognition of creatine by the imprinted polymer was found to be specific via non
      covalent (electrostatic) imprinting. The creatine binding could easily be
      detected by differential pulse, cathodic stripping voltammetric signal at
      optimised operational conditions: accumulation potential -0.01 V (versus
      Ag/AgCl), polymer deposition time 15s, template accumulation time 60s, pH 7.1
      (supporting electrolyte< or =5 x 10(-4)M NaOH), scan rate 10 mV s(-1), pulse
      amplitude 25 mV. The modified sensor in the present study was found to be highly
      reproducible and selective with detection limit 0.11 ng mL(-1) of creatine. Cross
      reactivity studies revealed no response to the addition of urea, creatinine and
      phenylalanine; however, some insignificant magnitude of current was observed for
      tryptophan and histidine in the test samples.

PMID- 17208427
TI  - Deregulated Ras signaling in developmental disorders: new tricks for an old dog.
AB  - Ras proteins regulate cell proliferation, survival and differentiation and are
      constitutively activated by somatic point mutations in many cancers. Previous
      studies of neurofibromatosis type 1 and Noonan syndrome also implicated
      hyperactive Ras in developmental disorders. Recently, germline mutations in H-RAS
      and K-RAS and in genes encoding other molecules in the Ras-Raf-MEK-ERK cascade
      were shown to underlie cases of Noonan, cardio-facio-cutaneous, and Costello
      syndromes. These disorders share phenotypic traits that include abnormal facial
      features, heart defects, and impaired growth and development. Many of these
      germline, disease-associated mutations encode novel Ras, Raf and MEK proteins.
      These studies underscore a crucial role of Ras signaling in human development.

PMID- 17208428
TI  - Jak2: normal function and role in hematopoietic disorders.
AB  - Janus kinase 2 (Jak2) associates with cytokine receptors and is essential for
      signal transduction by mediating tyrosine phosphorylation. Kinase activity is
      regulated by a series of interactions beginning with the requirement to bind to
      specific domains in receptors, suppression of activation by the pseudokinase
      domain, and the requirement for phosphorylation within the activation loop.
      Recent studies have implicated de-regulation of Jak2 kinase activity by
      chromosomal translocations in hematopoietic tumors and mutations within the
      pseudokinase domain in a spectrum of myeloproliferative diseases.

PMID- 17208429
TI  - The oncogenic roles of p53 mutants in mouse models.
AB  - Tumors associated with p53 usually contain missense mutations in the p53 tumor
      suppressor gene rather than deletions of p53, suggesting a growth advantage for
      cells with missense mutations. The oncogenic roles of p53 mutants have been
      examined extensively in cell lines. Mouse models that inherit p53 mutations
      expressed at physiological levels have now been generated to examine the
      activities of mutant p53 upon tumorigenesis in vivo. Mice with p53 mutations
      develop tumor spectrums and metastatic phenotypes different from those of mice
      with a p53-null allele. Embryo fibroblasts with mutant p53 also show increased
      proliferative and transformation properties. One mechanism for this gain-of
      function potential is the inhibition of function of the p53 family members p63
      and p73.

PMID- 17208430
TI  - New insight into BRAF mutations in cancer.
AB  - There has been much recent progress in our understanding of the role played by
      the RAS-RAF-MEK-ERK cascade in human cancer. RAS is an oncogene and this pathway
      is known to promote proliferation and malignant transformation. More recently,
      however, RAF has become the focus of attention, particularly in melanoma, where
      approximately 70% of cases carry mutations in the BRAF gene. The majority of the
      mutations in BRAF in cancer are activating, but rare mutants that cannot activate
      MEK have provided new insight into RAF signalling networks that exist in cancer
      and normal cells. Surprisingly, germline mutations in BRAF that occur in rare
      genetic syndromes have also recently been described. The induction of BRAF
      mutations in melanoma depends on the type of UV exposure that the skin receives,
      and some studies have suggested the existence of susceptibility loci that make it
      more likely that some individuals will acquire these mutations. Importantly,
      genetic profiling and microarray studies have provided insight into the spectrum
      of melanomas in which BRAF plays a role and also revealed intriguing new data
      that could be important for the diagnosis and treatment of human cancers.

PMID- 17208431
TI  - Cell cycle kinases in cancer.
AB  - Cell division in mammalian cells is driven by protein kinases that regulate
      progression through the various phases of the cell cycle. Cyclin-dependent
      kinases (Cdks) regulate cell cycle commitment, DNA synthesis and the onset of
      mitosis. Kinases of the Aurora, Polo and Nek families participate in the
      centrosome cycle and modulate spindle function. Additional kinases such as Bub1,
      BubR1 and Mps1 regulate the spindle assembly checkpoint. It has been well
      established that misregulation of Cdks is one of the most frequent alterations in
      human cancer. Recent evidence indicates that mutations involving mitotic kinases
      are also linked to tumor development. These findings suggest novel strategies to
      use cell cycle kinases as targets for therapeutic intervention.

PMID- 17208432
TI  - The many ways of Wnt in cancer.
AB  - More than 20 years ago, the oncogenicity of a Wnt ligand was revealed in a series
      of experiments originating with random proviral integration in mice. The
      significance of Wnt signaling in human cancer has since been buttressed by the
      identification of mutations in genes coding for the Wnt pathway components Axin,
      APC, and beta-catenin. This review summarizes the reported genetic defects in the
      Wnt pathway, with an emphasis on their functional contribution to human tumor
      progression.

PMID- 17208433
TI  - Hypoxia-inducible factors: central regulators of the tumor phenotype.
AB  - Low oxygen levels are a defining characteristic of solid tumors, and responses to
      hypoxia contribute substantially to the malignant phenotype. Hypoxia-induced gene
      transcription promotes characteristic tumor behaviors, including angiogenesis,
      invasion, metastasis, de-differentiation and enhanced glycolytic metabolism.
      These effects are mediated, at least in part, by targets of the hypoxia-inducible
      factors (HIFs). The HIFs function as heterodimers comprising an oxygen-labile
      alpha-subunit and a stable beta-subunit also referred to as ARNT. HIF-1alpha and
      HIF-2alpha stimulate the expression of overlapping as well as unique
      transcriptional targets, and their induction can have distinct biological
      effects. New targets and novel mechanisms of dysregulation place the HIFs in an
      ever more central role in tumor biology and have led to development of
      pharmacological inhibitors of their activity.

PMID- 17208434
TI  - KIT mutations in GIST.
AB  - Most gastrointestinal stromal tumors (GISTs) contain oncogenic KIT or PDGFRA
      receptor tyrosine kinase mutations. These rare neoplasms are remarkably sensitive
      to the KIT and PDGFRA kinase inhibitors imatinib (also known as Gleevec) and
      sunitinib (Sutent), which have recently been approved as the standard therapeutic
      courses for patients with inoperable GIST. However, most GIST patients eventually
      develop clinical resistance to imatinib and sunitinib. Imatinib and sunitinib
      resistance generally result from secondary mutations in the KIT and/or PDGFRA
      kinase domains. Preclinical studies suggest that imatinib and sunitinib resistant
      mutations can be treated using more potent kinase inhibitors, such as nilotinib,
      which inactivate the mutant kinase proteins. Alternately, the mutant kinase
      proteins can be targeted using HSP90 inhibitors, which result in degradation of
      activated KIT and/or PDGFRA, or using KIT transcriptional repressors, such as
      flavopiridol.

PMID- 17208435
TI  - Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu).
AB  - Targeting of epidermal growth factor receptor (EGFR) and HER2 is a proven anti
      cancer strategy. However, heterodimerisation, compensatory 'crosstalk' and
      redundancy exist in the ErbB network, and there is therefore a sound scientific
      rationale for dual inhibition of EGFR and HER2. Trials of approved agents in
      combination, for example trastuzumab and cetuximab, are underway. There is also a
      new generation of small molecule tyrosine kinase inhibitors (TKIs) and monoclonal
      antibodies (mABs) that target two or more ErbB receptors. Lapatinib, a TKI of
      EGFR and HER2, has shown clinical benefit in trastuzumab refractory breast cancer
      and is poised for FDA approval. Other agents include BIBW-2992 and HKI-272,
      irreversible TKIs of EGFR and HER2, and pertuzumab, a heterodimerisation
      inhibitor of EGFR and HER2.

PMID- 17208436
TI  - 11-Beta hydroxysteroid dehydrogenase type 2 expression in white adipose tissue is
      strongly correlated with adiposity.
AB  - Glucocorticoid action within the cells is regulated by the levels of
      glucocorticoid receptor (GR) expression and two enzymes, 11-beta hydroxysteroid
      dehydrogenase type 1 (11betaHSD1), which converts inactive to active
      glucocorticoids, and 11-beta hydroxysteroid dehydrogenase type 2 (11betaHSD2),
      which regulates the access of active glucocorticoids to the receptor by
      converting cortisol/corticosterone to the glucocorticoid-inactive form
      cortisone/dehydrocorticosterone. Male Wistar rats developed obesity by being fed
      a high-fat diet for 56 days, and GR, 11betaHSD1 and 11betaHSD2 gene expression
      were compared with control-diet fed animals. Gene expression analysis of
      11betaHSD1, 11betaHSD2 and GR were performed by RT-PCR in subcutaneous and
      retroperitoneal adipose tissue. High-fat fed animals overexpressed 11betaHSD2 in
      subcutaneous but not in retroperitoneal fat. Interestingly, mRNA levels strongly
      correlated in both tissues with different parameters related to obesity, such as
      body weight, adiposity and insulin resistance, suggesting that this gene is a
      reliable marker of adiposity in this rat model of obesity. Thus, 11betaHSD2 is
      expressed in adipose tissue by both adipocytes and stromal-vascular cells, which
      suggests that this enzyme may play an important role in preventing fat
      accumulation in adipose tissue.

PMID- 17208437
TI  - 1alpha,25(OH)2-vitamin D3 membrane-initiated calcium signaling modulates
      exocytosis and cell survival.
AB  - 1alpha,25(OH)(2)-vitamin D(3) (1,25D) is considered a bone anabolic hormone.
      1,25D actions leading to bone formation involve gene transactivation, on one
      hand, and modulation of cytoplasmic signaling, on the other. In both cases, a
      functional vitamin D receptor (VDR) appears to be required. Here we study 1,25D
      stimulated calcium signaling that initiates at the cell membrane and leads to
      exocytosis of bone materials and increased osteoblast survival. We found that
      rapid 1,25D-induction of exocytosis couples to cytoplasmic calcium increase in
      osteoblastic ROS 17/2.8 cells. In addition, we found that elevation of
      cytoplasmic calcium concentration is involved in 1,25D anti-apoptotic effects via
      Akt activation in ROS 17/2.8 cells and non-osteoblastic CV-1 cells. In both
      cases, 1,25D-stimulated elevation of intracellular calcium is due in part to
      activation of L-type Ca(2+) channels. We conclude that 1,25D bone anabolic
      effects that involve increased intracellular Ca(2+) concentration in osteoblasts
      can be explained at two levels. At the single-cell level, 1,25D promotes Ca(2+)
      dependent exocytotic activities. At the tissue level, 1,25D protects osteoblasts
      from apoptosis via a Ca(2+)-dependent Akt pathway. Our studies contribute to the
      understanding of the molecular basis of bone diseases characterized by decreased
      bone formation and mineralization.

PMID- 17208438
TI  - A meta-analysis of second cancers after a diagnosis of nonmelanoma skin cancer:
      additional evidence that solar ultraviolet-B irradiance reduces the risk of
      internal cancers.
AB  - BACKGROUND: Nearly 20 types of cancer have been found to be inversely correlated
      with solar ultraviolet-B (UVB) levels determined geographically in ecologic
      studies, assuming that personal solar UVB irradiances were directly related to
      July solar UVB doses. This assumption has been questioned. METHODS: Rates of
      second cancer after diagnosis of nonmelanoma skin cancer (NMSC) from the
      literature were used in linear regression analyses. The risk modification of NMSC
      due to smoking was accounted for by comparing second cancer risk ratios (RRs)
      with lung cancer RRs in regression analysis for each cancer. RESULTS: For a
      diagnosis of squamous cell carcinoma, RRs for subsequent colon, gastric, and
      rectal cancers were significantly reduced, with that for renal cancer being
      marginally insignificant. For NMSC, RRs for cervical, esophageal, gastric, and
      rectal cancer were significantly reduced; those for colon and gallbladder cancer
      were marginally insignificant, while those for female breast, laryngeal, ovarian,
      renal, and uterine corpus cancers were insignificantly reduced; RRs for lip and
      salivary gland cancers and melanoma were significantly increased. Melanoma was
      inversely correlated with lung cancer. CONCLUSION: These results provide nearly
      direct evidence that solar UVB irradiance reduces the risk of many internal
      cancers. The likely mechanism is production of Vitamin D.

PMID- 17208439
TI  - Urinary excretion of 5(10)-estrene-3beta,17alpha-diol and estrone by the female
      horse: complementary indicators of early pregnancy screened with regard to a
      putative anabolic doping practice.
AB  - Rules of horse racing stipulate that pregnant mares may compete under definite
      conditions of date, because early pregnant status may be misused for the sake of
      enhancing physical performance by putative anabolic steroid action. Screening for
      pregnancy is generally performed by plasma equine gonadotrophin (eCG)
      immunoassay, which covers the period between Days 40 and 120. In common screening
      for urinary anabolic steroids performed by gas chromatography-mass spectrometry,
      inclusion of two complementary criteria, i.e. the evaluation of total conjugates
      of 5(10)-estrene-3beta,17alpha-diol (EED) and estrone (E1), can easily be
      performed. Although EED and E1 have no anabolic property per se in the horse,
      assessing these two markers may be helpful in the period comprised between Days
      70 and 250, thereby prolonging the detection period behind that of eCG. Peak
      values of EED and E1 are then attained, so that visual inspection of
      chromatographic tracings remains in general sufficient as a diagnostic tool.
      Comparison of EED and E1 during pregnancy and in an estrus cycle indicates a
      drastic difference in the attained excretion values, attributable to either the
      placenta or the ovarian follicle. The identity of EED has been proven by GC-MS(n)
      in urine and in placental tissue.

PMID- 17208440
TI  - Bioremediation of pulp and paper mill effluent by a novel fungal consortium
      isolated from polluted soil.
AB  - Two basidiomycetous fungi (Merulius aureus syn. Phlebia sp. and an unidentified
      genus) and a deuteromycetous fungus (Fusarium sambucinum Fuckel MTCC 3788) were
      isolated from soils affected with effluents of a pulp and paper mill over several
      years. These isolates were immobilized on nylon mesh and the consortium was used
      for bioremediation of pulp and paper mill effluent in a continuously aerated
      bench-top bioreactor. The treatment resulted in the reduction of color, lignin
      and COD of the effluent in the order of 78.6%, 79.0% and 89.4% in 4 days. A major
      part of reductions in these parameters occurred within first 24h of the
      treatment, which was also characterized by a steep decline in the pH of the
      effluent. During this period, total dissolved solids, electrical conductivity and
      salinity of the effluent also registered marked decline. It is pertinent to note
      that this is the first report of bioremediation of pulp and paper mill effluent
      by an immobilized fungal consortium.

PMID- 17208441
TI  - Catalytic cracking of palm oil for the production of biofuels: optimization
      studies.
AB  - Oil palm is widely grown in Malaysia. Palm oil has attracted the attention of
      researchers to develop an 'environmentally friendly' and high quality fuel, free
      of nitrogen and sulfur. In the present study, the catalytic cracking of palm oil
      to biofuel was studied over REY catalyst in a transport riser reactor at
      atmospheric pressure. The effect of reaction temperature (400-500 degrees C),
      catalyst/palm oil ratio (5-10) and residence time (10-30s) was studied over the
      yield of bio-gasoline and gas as fuel. Design of experiments was used to study
      the effect of operating variables over conversion of palm oil and yield of
      hydrocarbon fuel. The response surface methodology was used to determine the
      optimum value of the operating variables for maximum yield of bio-gasoline
      fraction in the liquid product obtained.

PMID- 17208442
TI  - Navigational strategies during fast walking: a comparison between trained
      athletes and non-athletes.
AB  - Many common activities such as walking in a shopping mall, moving in a busy
      subway station, or even avoiding opponents during sports, all require different
      levels of navigational skills. Obstacle circumvention is beginning to be
      understood across age groups, but studying trained athletes with greater levels
      of motor ability will further our understanding of skillful adaptive locomotor
      behavior. The objective of this work was to compare navigational skills during
      fast walking between elite athletes (e.g. soccer, field hockey, basketball) and
      aged-matched non-athletes under different levels of environmental complexity in
      relation to obstacle configuration and visibility. The movements of eight women
      athletes and eight women non-athletes were measured as they walked as fast as
      possible through different obstacle courses in both normal and low lighting
      conditions. Results showed that athletes, despite similar unobstructed maximal
      speeds to non-athletes, had faster walking times during the navigation of all
      obstructed environments. It appears that athletes can process visuo-spatial
      information faster since both groups can make appropriate navigational decisions,
      but athletes can navigate through complex, novel, environments at greater speeds.
      Athletes' walking times were also more affected by the low lighting conditions
      suggesting that they normally scan the obstructed course farther ahead. This
      study also uses new objective measures to assess functional locomotor capacity in
      order to discriminate individuals according to their level of navigational
      ability. The evaluation paradigm and outcome measures developed may be applicable
      to the evaluation of skill level in athletic training and selection, as well as
      in gait rehabilitation following impairment.

PMID- 17208443
TI  - Tyrosine phosphorylation: an emerging regulatory device of bacterial physiology.
AB  - Tyrosine phosphorylation is a key device in numerous cellular functions in
      eukaryotes, but in bacteria this protein modification was largely ignored until
      the mid-1990s. The first conclusive evidence of bacterial tyrosine
      phosphorylation came only a decade ago. Since then, several tyrosine kinases
      exhibiting unexpected features have been identified in a variety of bacteria.
      These enzymes use homologues of Walker motifs of nucleotide-binding proteins for
      their catalytic mechanism, thus defining an idiosyncratic type of bacterial
      tyrosine kinases. Recently, bacterial tyrosine kinases have been found to
      phosphorylate an increasing list of endogenous protein substrates. This discovery
      contributes to the emerging picture that bacterial tyrosine phosphorylation is an
      important regulatory arsenal of bacterial physiology in addition to the classical
      serine/threonine kinases, and the 'two-component' and phosphotransferase systems.

PMID- 17208444
TI  - How do ALS-associated mutations in superoxide dismutase 1 promote aggregation of
      the protein?
AB  - More than 100 different mutations in the gene encoding copper-zinc superoxide
      dismutase (SOD1) cause familial forms of amyotrophic lateral sclerosis (ALS)--a
      fatal neurodegenerative disease in which aggregation of the SOD1 protein is
      considered to be the primary mode of pathogenesis. Recent results show that these
      mutations have remarkably diverse and unexpected effects on the structure,
      activity and native state stability of SOD1. Intriguingly, many mutations seem to
      have no measurable effect on the biophysical and biochemical properties of SOD1,
      except for decreasing the net charge of the protein. Thus, it seems likely that
      different ALS-associated mutations promote SOD1 aggregation by fundamentally
      distinct mechanisms. Understanding this complexity has implications for drug
      development and treatment of the disease.

PMID- 17208445
TI  - Synthesis and antimycobacterial evaluation of benzofurobenzopyran analogues.
AB  - We recently reported that 3,3-dimethyl-3H-benzofuro[3,2,f][1]-benzopyran and its
      hydrogenated analogue are selective in vitro inhibitors of mycobacterial growth.
      However, their lack of in vivo activity on a murine model of Mycobacterium
      tuberculosis infection due to their poor bioavailability led to a structure
      activity relationship investigation. We wish to report here the preparation of
      some structural analogues along with their biological effect on the growth of
      Mycobacterium smegmatis, M. tuberculosis, as well as on VERO cells for the most
      active compound.

PMID- 17208446
TI  - Rare-earth elements in Egyptian granite by instrumental neutron activation
      analysis.
AB  - The mobilization of rare-earth elements (REEs) in the environment requires
      monitoring of these elements in environmental matrices, in which they are mainly
      present at trace levels. The similarity in REEs chemical behavior makes the
      separate determination of each element by chemical methods difficult;
      instrumental neutron activation analysis (INAA), based on nuclear properties of
      the elements to be determined, is a method of choice in trace analysis of REEs
      and related elements. Therefore, INAA was applied as a sensitive nondestructive
      analytical tool for the determination of REEs to find out what information could
      be obtained about the REEs of some Egyptian granite collected from four locations
      in Aswan area in south Egypt as follows wadi El-Allaqi, El-Shelal, Gabel Ibrahim
      Pasha and from Sehyel Island and to estimate the accuracy, reproducibility and
      detection limit of NAA method in case of the given samples. The samples were
      properly prepared together with standards and simultaneously irradiated in a
      neutron flux of 7 x 10(11)n/cm(2)s in the TRIGA Mainz research reactor
      facilities. The following elements have been determined: La, Ce, Nd, Sm, Eu, Yb
      and Lu. The gamma spectra was collected by HPGe detector and the analysis was
      done by means of computerized multichannel analyzer. The X-ray fluorescence (XRF)
      was also used.

PMID- 17208447
TI  - Potential roles of the prokineticins in reproduction.
AB  - Prokineticins are multifunctional secreted proteins that were originally
      identified as regulators of intestinal contraction but subsequently shown to
      affect vascular function, hyperalgesia, spermatogenesis, neuronal survival,
      circadian rhythm, nociception, feeding behaviour, immune responses,
      haematopoiesis and the development of the olfactory and gonadotropin-releasing
      hormone systems. Their role in the reproductive tract is still not fully
      elucidated, although they are reputed to increase microvascular permeability.
      Expression of prokineticins and their receptors has been reported in the ovary,
      uterus, placenta, testis and prostate. Their expression has also been reported in
      various pathologies of the reproductive tract, and future studies will highlight
      whether inhibition of prokineticin function in these pathologies would be a
      useful therapeutic target.

PMID- 17208448
TI  - A new expression of diabetes: double diabetes.
AB  - Diabetes is on the increase worldwide. The incidence of both type 1 and type 2
      diabetes has shown a rise, in parallel with a notable increase in the incidence
      of a new expression of the disease in children and adolescents, with the
      characteristics of a mixture of the two types of diabetes, and referred to as
      'double diabetes'. Insulin resistance and obesity, together with the presence of
      markers of pancreatic autoimmunity - namely, autoantibodies to islet cell
      antigens - typically define this condition. However, recognition of double
      diabetes can pose problems. In most cases, a reduction in the 'autoimmune load'
      and an increase in the 'metabolic load' are helpful for attaining a correct
      diagnosis in a diabetic child.

PMID- 17208449
TI  - Gonadotropin-releasing hormone neuron remodeling: causal for puberty onset?
AB  - The concept that regulation of neurosecretory function is coupled to structural
      remodeling of the underlying neuronal network is not new but the developmental
      changes in the hypothalamic gonadotropin-releasing hormone system of the
      postnatal male mouse recently reported by Herbison's group are unexpectedly
      marked, involving both the soma and dendrite. Does this plasticity underlie the
      pubertal increase in pulsatile gonadotropin-releasing hormone release that takes
      the animal into adulthood?

PMID- 17208450
TI  - Impaired hippocampal synaptic transmission and plasticity in mice lacking
      fibroblast growth factor 14.
AB  - Humans with an autosomal dominant missense mutation in fibroblast growth factor
      14 (FGF14) have impaired cognitive abilities and slowly progressive
      spinocerebellar ataxia. To explore the mechanisms that may account for this
      phenotype, we show that synaptic transmission at hippocampal Schaffer collateral
      CA1 synapses and short- and long-term potentiation are impaired in Fgf14-/- mice,
      indicating abnormalities in synaptic plasticity. Examination of CA1 synapses in
      Fgf14-/- mice show a significant reduction in the number of synaptic vesicles
      docked at presynaptic active zones and a significant synaptic fatigue/depression
      during high/low-frequency stimulation. In addition, mEPSC frequency, but not
      amplitude, is decreased in hippocampal neurons derived from Fgf14-/- mice.
      Furthermore, expression of selective synaptic proteins in Fgf14-/- mice was
      decreased. These findings suggest a novel role for FGF14 in regulating synaptic
      plasticity via presynaptic mechanisms by affecting the mobilization, trafficking,
      or docking of synaptic vesicles to presynaptic active zones.

PMID- 17208451
TI  - Hyperphosphorylation of tau and neurofilaments and activation of CDK5 and ERK1/2
      in PTEN-deficient cerebella.
AB  - Inherited mutations to the tumor suppressor PTEN sporadically lead to cerebellar
      gangliocytoma characterized by migration defects. This has been modeled by CNS
      specific PTEN ablation in mice, but the underlying mechanism cannot be explained
      by the known role of PTEN in Akt/PKB inactivation. Here we show that the loss of
      PTEN in mouse cerebellar neurons causes neurodegeneration by hyperphosphorylation
      of tau and neurofilaments, and activation of Cdk5 and pERK1/2, suggesting that
      dysregulation of the PTEN/pAkt pathway can mediate neurodegeneration.

PMID- 17208452
TI  - Functional expression of recombinant human stefin A in mammalian and bacterial
      cells.
AB  - Recombinant human cysteine protease inhibitor, stefin A, was expressed in both
      Escherichia coli and BS-C-1 monkey kidney cells utilizing pET and recombinant
      vaccinia virus systems, respectively. The expressed protein was purified and
      analyzed by SDS-PAGE and Western blot analysis utilizing a polyclonal antibody
      against rat cystatin alpha. In both cases the purified protein appeared as a
      single band corresponding to the molecular weight of stefin A ( approximately
      10kDa). Viability of the expressed stefin A was determined by the inhibition of
      the plant cysteine protease, papain. Recombinant human stefin A expressed in both
      E. coli and BS-C-1 cells, was shown to almost completely inhibit papain. The
      expression of a fully functional recombinant human stefin A in the bacterial
      system provides a highly efficient tool for the production of large quantities of
      the protein. This can be an important tool in kinetic studies as well as in
      production of antibodies for other analytical studies (immunoblot,
      immunohistochemical studies, etc.). Expression in the mammalian cells, on the
      other hand, can provide a significant research tool to study the functional roles
      of stefin A in mammalian systems such as regulation of cysteine proteases.

PMID- 17208453
TI  - Purification and characterization of carbonic anhydrase of rice (Oryza sativa L.)
      expressed in Escherichia coli.
AB  - Rice carbonic anhydrase (CA) was successfully expressed as a glutathione-S
      transferase (GST) fusion protein in an Escherichia coli expression system. The
      optimal induction concentration of IPTG and growth temperature was found to be
      1.0mM and 28 degrees C. To obtain milligram amounts of homogeneous active
      recombinant proteins, 150mM NaCl and Mg-ATP solution were used during the
      purification procedures. After improving the conditions of expression and the
      purification procedures, final yield of recombinant proteins was 1.3mg/g wet cell
      weight after enzymatic cleavage of the GST tag, and the molecular weight was
      about 29kDa. The purified protein had CO(2) hydration activity, and had no
      detectable esterase activity in vitro. Addition of zinc improved the CO(2)
      hydration activity of the rice CA produced by E. coli. The effects of
      acetazolamide (AZ) and the anions N3-, NO3-, I(-), Br(-), and Cl(-) on CO(2)
      hydration activity of CA were studied. AZ and N3- were found to be strong
      inhibitors of rice CA. The inhibitory activity of AZ and ions was in the order
      AZ>N3->NO3->I(-)>Br(-)>Cl(-).

PMID- 17208454
TI  - Cox17, a copper chaperone for cytochrome c oxidase: expression, purification, and
      formation of mixed disulphide adducts with thiol reagents.
AB  - Copper chaperone for cytochrome c oxidase (Cox17) is a 7 kDa copper-binding
      protein, which facilitates incorporation of copper ions into Cu(A) site of
      cytochrome c oxidase. Cox17 contains six conserved Cys residues and occurs in
      three different oxidative states, which display different metal-binding
      properties and stability. In the present study, we have elaborated technologies
      for production of partially oxidized human recombinant Cox17 in a bacterial
      expression system and purification of fully oxidized Cox17. For this purpose we
      used Escherichia coli Origami strain, which is deficient in thioredoxin and
      thioredoxin reductase systems and allows formation of disulfide bonds in
      cytoplasmic proteins. Fully oxidized Cox17 was purified by a simplified two-step
      procedure including gel filtration and cation exchange chromatography. By using
      mass spectrometry we demonstrated that application of 2-mercaptoethanol (2-ME)
      during purification leads to formation of its mixed disulfide adducts with Cox17.
      Moreover, partially reduced Cox17 can form mixed disulfide adducts also with the
      cellular reducing agent glutathione, which abolishes copper-binding ability of
      partially reduced Cox17.

PMID- 17208455
TI  - An attenuated plasmid-cured strain of Aeromonas hydrophila elicits protective
      immunity in Clarias batrachus L.
AB  - Wild type Aeromonas hydrophila (Strain AO1) isolated from the lesions of
      ulcerative disease syndrome (UDS) affected fish bears a 21 kb virulence plasmid.
      With plasmid curing the isolates became attenuated and failed to induce fatal
      haemorrhagic ulcers in fish. The objective of the present work was to check the
      immunogenicity of these plasmid-cured derivatives and determine whether such
      strains could be used as candidate antigens for eliciting protective immunity to
      A. hydrophila infections in the Indian catfish Clarias batrachus L. It was
      observed that the plasmid-cured strains were immunogenic since infection with
      live plasmid-cured AO1 isolates generated effective T cell responses and led to
      increase in serum antibacterial agglutinin titres in C. batrachus. Plasmid-cured
      AO1 strains injected into C. batrachus could disseminate into head kidney (HK)
      and spleen but never attained the same bacterial loads obtained with wild type
      AO1 and were cleared rapidly from the host. Immunisation with plasmid-cured
      bacteria prevented systemic spread and conferred protection against lethal
      challenge (10 x LD(50)) with wild type A. hydrophila as well as other pathogenic
      strains of Aeromonas sp. These results demonstrate the potentials of plasmid
      cured A. hydrophila derivatives as candidate antigens for eliciting protective
      immunity in fish and the possibility of using such isolates as shuttle vectors in
      aquaculture.

PMID- 17208456
TI  - Supra dietary levels of vitamins C and E enhance antibody production and immune
      memory in juvenile milkfish, Chanos chanos (Forsskal) to formalin-killed Vibrio
      vulnificus.
AB  - Juveniles of milkfish, Chanos chanos (Forsskal), were fed two independent supra
      dietary levels of vitamins C (500 and 1500 mg kg(-1) feed, T1 and T2) and E (50
      and 150 mg kg(-1), T3 and T4). Milkfish fed diets with supra (in addition to the
      vitamins present in the control diet) and normal levels (T5 containing 90 and
      1.2mg of vitamins C and E, respectively, kg(-1) of feed) of vitamins were
      immunized (ip) with formalin-killed Vibrio vulnificus (FKVV). Priming and booster
      antibody responses to the injected bacterin were significantly (P<0.05) better in
      the milkfish juveniles fed supra dietary levels. Survival response of the
      experimental fish fed supra dietary levels of vitamins (T1, T2 and T3) was
      significantly (P<0.01) better than that of the control set. Protective response
      against virulent bacterial challenge of the vaccinated fish fed vitamin
      supplemented diets (T2 and T3) was better than the control (T5) and T1 and T4.
      Memory factor reflecting immunological memory was superior in the fish fed
      vitamin-supplemented diets. Diets supplemented with either 1500 mg of Vitamin C
      or 50mg of Vitamin E kg(-1) produced the best antibody responses, final survival
      and protective response upon challenge. No conclusive inferences could be drawn
      on the growth responses from the experiment.

PMID- 17208457
TI  - Fatigue effects on tracking performance and muscle activity.
AB  - It has been suggested that fatigue affects proprioception and consequently
      movement accuracy, the effects of which may be counteracted by increased muscle
      activity. To determine the effects of fatigue on tracking performance and muscle
      activity in the M. extensor carpi radialis (ECR), 11 female participants
      performed a 2-min tracking task with a computer mouse, before and immediately
      after a fatiguing wrist extension protocol. Tracking performance was
      significantly affected by fatigue. Percentage time on target was significantly
      lower in the first half of the task after the fatigue protocol, but was
      unaffected in the latter half of the task. Mean distance to target and the
      standard deviation of the distance to target were both increased after the
      fatigue protocol. The changed performance was accompanied by higher peak EMG
      amplitudes in the ECR, whereas the static and the median EMG levels were not
      affected. The results of this study showed that subjects changed tracking
      performance when fatigued in order to meet the task instruction to stay on
      target. Contrary to our expectations, this did not lead to an overall higher
      muscle activity, but to a selective increase in peak muscle activity levels of
      the ECR.

PMID- 17208458
TI  - Fatigue of the plantar intrinsic foot muscles increases navicular drop.
AB  - Our purpose was to assess the effect of foot intrinsic muscle fatigue on
      pronation, as assessed with navicular drop, during static stance. Twenty-one
      healthy young adults participated. Navicular drop was measured before and after
      fatiguing exercise of the plantar foot intrinsic muscles. Surface
      electromyography of the abductor hallucis muscle was recorded during maximum
      voluntary isometric contractions (MVIC) in order to find the baseline median
      frequency (MedF). Subjects then performed sets of 75 repetitions of isotonic
      flexion contractions of the intrinsic foot muscles against a 4.55 kg weight on a
      custom pulley system. After each set an MVIC was performed to track shifts in
      MedF. After a MedF shift of at least 10%, navicular drop measurements were
      repeated. Subjects exhibited 10.0+/-3.8mm of navicular drop at baseline and
      11.8+/-3.8mm after fatigue (p<0.0005). The change in navicular drop was
      significantly correlated with change in MedF (r=.47, p=.03). The intrinsic foot
      muscles play a role in support of the medial longitudinal arch in static stance.
      Disrupting the function of these muscles through fatigue resulted in an increase
      in pronation as assessed by navicular drop.

PMID- 17208459
TI  - Towards natural stimulation in fMRI--issues of data analysis.
AB  - In search for suitable tools to study brain activation in natural environments,
      where the stimuli are multimodal, poorly predictable and irregularly varying, we
      collected functional magnetic resonance imaging data from 6 subjects during a
      continuous 8-min stimulus sequence that comprised auditory (speech or tone pips),
      visual (video clips dominated by faces, hands, or buildings), and tactile finger
      stimuli in blocks of 6-33 s. Results obtained by independent component analysis
      (ICA) and general-linear-model-based analysis (GLM) were compared. ICA separated
      in the superior temporal gyrus one independent component (IC) that reacted to all
      auditory stimuli and in the superior temporal sulcus another IC responding only
      to speech. Several distinct and rather symmetric vision-sensitive ICs were found
      in the posterior brain. An IC in the V5/MT region reacted to videos depicting
      faces or hands, whereas ICs in the V1/V2 region reacted to all video clips,
      including buildings. The corresponding GLM-derived activations in the auditory
      and early visual cortices comprised sub-areas of the ICA-revealed activations.
      ICA separated a prominent IC in the primary somatosensory cortex whereas the GLM
      based analysis failed to show any touch-related activation. "Intrinsic"
      components, unrelated to the stimuli but spatially consistent across subjects,
      were discerned as well. The individual time courses were highly consistent in
      sensory projection cortices and more variable elsewhere. The ability to
      differentiate functionally meaningful composites of activated brain areas and to
      straightforwardly reveal their temporal dynamics renders ICA a sensitive tool to
      study brain responses to complex natural stimuli.

PMID- 17208460
TI  - A multivariate analysis of neuroanatomic relationships in a genetically
      informative pediatric sample.
AB  - An important component of brain mapping is an understanding of the relationships
      between neuroanatomic structures, as well as the nature of shared causal factors.
      Prior twin studies have demonstrated that much of individual differences in human
      anatomy are caused by genetic differences, but information is limited on whether
      different structures share common genetic factors. We performed a multivariate
      statistical genetic analysis on volumetric MRI measures (cerebrum, cerebellum,
      lateral ventricles, corpus callosum, thalamus, and basal ganglia) from a
      pediatric sample of 326 twins and 158 singletons. Our results suggest that the
      great majority of variability in cerebrum, cerebellum, thalamus and basal ganglia
      is determined by a single genetic factor. Though most (75%) of the variability in
      corpus callosum was explained by additive genetic effects these were largely
      independent of other structures. We also observed relatively small but
      significant environmental effects common to multiple neuroanatomic regions,
      particularly between thalamus, basal ganglia, and lateral ventricles. These
      findings are concordant with prior volumetric twin studies and support radial
      models of brain evolution.

PMID- 17208461
TI  - Virtual definition of neuronal tissue by cluster analysis of multi-parametric
      imaging (virtual-dot-com imaging).
AB  - Individual mapping of cerebral, morphological, functionally related structures
      using MRI was carried out using a new multi-contrast acquisition and analysis
      framework, called virtual-dot-com imaging. So far, conventional anatomical MRI
      has been able to provide gross segmentation of gray/white matter boundaries and a
      few sub-cortical structures. By combining a handful of imaging contrasts
      mechanisms (T1, T2, magnetization transfer, T2* and proton density), we were able
      to further segment sub-cortical tissue to its sub-nuclei arrangement, a
      segmentation that is difficult based on conventional, single-contrast MRI. Using
      an automatic four-step image and signal processing algorithm, we segmented the
      thalamus to at least 7 sub-nuclei with high similarity across subjects and high
      statistical significance within subjects (p<0.0001). The identified sub-nuclei
      resembled the known anatomical arrangement of the thalamus given in various
      atlases. Each cluster was characterized by a unique MRI contrast fingerprint.
      With this procedure, the weighted proportions of the different cellular
      compartments could be estimated, a property available to date only by
      histological analysis. Each sub-nucleus could be characterized in terms of
      normalized MRI contrast and compared to other sub-nuclei. The different weights
      of the contrasts (T1/T2/T2*/PD/MT, etc.) for each sub-nuclei cluster might
      indicate the intra-cluster morphological arrangement of the tissue that it
      represents. The implications of this methodology are far-ranging, from non
      invasive, in vivo, individual mapping of histologically distinct brain areas to
      automatic identification of pathological processes.

PMID- 17208462
TI  - Neural evidence for Reference-dependence in real-market-transactions.
AB  - Human decision making has become one of the major research-foci in economics,
      marketing and in neuroscience. This study integrates perspectives from these
      disciplines by examining neurophysiological correlates to Reference-dependence of
      utility evaluations in real market contexts both before and after choice. First,
      by comparing buying and selling decisions, we observe an activation of the
      amygdala only in the latter. We interpret this as loss aversion with respect to
      prior possessions. This finding contributes to the settling of an ongoing
      fundamental dispute in economic theory by indicating the absence of loss aversion
      for money in routine transactions. Second, ex post satisfaction statements are
      accompanied by an activation of the reward processing orbitofrontal cortex, if
      the evaluation context is framed by a high external reference price instead of a
      lower internal reference price. This indicates a nonrational Reference-dependence
      -despite the neoclassical view of a rational Homo Economicus--of satisfaction
      measures and challenges a central marketing variable.

PMID- 17208463
TI  - Evolutionary dynamics of Waxy and the origin of hexaploid Spartina species
      (Poaceae).
AB  - We investigated the evolutionary dynamics of duplicated copies of the granule
      bound starch synthase I gene (GBSSI or Waxy) within polyploid Spartina species.
      Molecular cloning, sequencing, and phylogenetic analyses revealed incongruences
      between the expected species phylogeny and the inferred gene trees. Some genes
      within species were more divergent than expected from ploidy level alone,
      suggesting the existence of paralogous sets of Waxy loci in Spartina.
      Phylogenetic analyses indicate that this paralogy originated from a duplication
      that occurred prior to the divergence of Spartina from other Chloridoideae. Gene
      tree topologies revealed three divergent homoeologous sequences in the hexaploid
      S. alterniflora that are consistent with the proposal of an allopolyploid origin
      of the hexaploid clade. Waxy sequences differ in insertion-deletion events in
      introns, which may be used to diagnose gene copies. Both paralogous and
      homoeologous coding regions appear to evolving under selective constraints.

PMID- 17208464
TI  - The role of geography and ecology in shaping the phylogeography of the speckled
      hummingbird (Adelomyia melanogenys) in Ecuador.
AB  - The Andes of South America contain one of the richest avifaunas in the world, but
      little is known about how this diversity arises and is maintained. Variation in
      mitochondrial DNA and morphology within the speckled hummingbird (Adelomyia
      melanogenys) was used to elucidate the phylogeographic pattern along an
      Ecuadorian elevational gradient, from the coastal cordillera to the inland Andean
      montane region. We examined sequence, climatic/remote sensing and morphological
      data to understand the effects of topography and ecology on patterns of
      variation. Populations on either side of the Andes are genetically divergent and
      were separated during a period that corresponds to the final stages of Andean
      uplift during the Pliocene. Despite isolation, these two populations were found
      to be morphologically similar suggesting a strong effect of stabilizing selection
      across ecologically similar Andean cloud forests, as assessed using climatic and
      remote sensing data. In contrast, little genetic divergence was found between
      coastal and west-Andean individuals, suggesting recent interruption of gene flow
      between these localities. However, coastal populations were found to inhabit
      different habitats compared to Andean populations as shown by climatic and remote
      sensing variables. Furthermore, coastal individuals had significantly longer
      bills compared to their montane relatives, indicative of differential directional
      selection and the influence of habitat differences in shaping phenotypic
      variation. Results highlight the role of both isolation and ecology in
      diversification in Ecuadorian montane regions, while suggesting the two may not
      always act in concert to produce divergence in adaptive traits.

PMID- 17208465
TI  - Improvement in quality of life after initiation of lamotrigine therapy in
      patients with epilepsy in a naturalistic treatment setting.
AB  - Quality of life is impaired in patients with epilepsy and can be improved by
      effective therapy. Randomised clinical trials have shown that lamotrigine
      treatment is associated with improved quality of life. However, little
      information is available on quality of life or treatment effects in patients with
      epilepsy in the general population. The objective of this study was to estimate
      the impact of lamotrigine on quality of life in a naturalistic treatment setting.
      The study included adult patients with epilepsy in whom lamotrigine therapy was
      initiated. Each subject completed the Quality of Life in Epilepsy Inventory
      (QOLIE)-31 quality of life questionnaire at inclusion and at a follow-up visit in
      the next 4 months. Demographic information and medical history were provided by
      the investigator. These were evaluated as potential determinants of change in
      quality of life using logistic regression. Three hundred and forty-one patients
      were evaluated, 192 starting lamotrigine in combination with another drug, 90 as
      a first-line monotherapy, 45 as a switch from another drug and 14 as a reduction
      to monotherapy from a previous combination. Baseline scores on the QOLIE-31
      ranged from 53.8 in the combination group to 69.5 in the first-line group. 34.6%
      of patients were considered to be responders, with no significant differences
      between treatment regimen. Most improvement was seen for the energy-fatigue and
      medication effects subscales and, for the first-line group, seizure worry.
      Seizure type was the only determinant of improvement of quality of life
      identified. In conclusion, lamotrigine treatment is associated with improved
      quality of life, regardless of treatment regimen.

PMID- 17208466
TI  - Coping strategies in epilepsy: 50 drug-resistant and 50 seizure-free patients.
AB  - We investigated the coping styles and their correlation to psycho-social
      functioning in two groups of patients, the first group with drug-resistant
      epilepsy and the second with well-controlled epilepsy. The instruments
      administered were the following: the Raven's Coloured Progressive Matrices (non
      verbal intelligence), the Echelle Toulousaine de Coping, ETC (coping styles), the
      Self-esteem Questionnaire (self-esteem), the Self-efficacy Questionnaire (social
      self-efficacy), a Quality of Life Measure and a semi-structured interview on
      psycho-social adjustment. We found a significant difference in coping responses
      between the two groups: drug-resistant patients seemed to adopt the "denial" and
      the "exclusion" strategies more (P<0.05). On the contrary, seizure-free subjects
      used the "control" strategy more (P<0.05). A significant correlation between
      disengagement patterns and poorer social outcomes was pointed out, while
      "control" was associated with better social adaptation. Our findings provide
      evidence of the importance of coping assessment, considering the influence of
      these strategies on the well being of patients. Offering psychological support to
      epilepsy patients should be considered when orientating the effectiveness of the
      patients' coping styles.

PMID- 17208467
TI  - A longitudinal analysis of serum cytokines in the Hartley guinea pig model of
      osteoarthritis.
AB  - OBJECTIVE: To evaluate chosen serum cytokines and their association with
      osteoarthritis (OA) in the guinea pig. METHODS: The levels of 18 cytokines were
      measured in Hartley guinea pig serum at time points ranging from 3 weeks to 18
      months of age. These levels were then tested for any correlation with total
      histology, and a comprehensive evaluation of these statistics was conducted using
      data previously collected from OA-resistant Strain 13 guinea pigs. RESULTS: After
      all cytokines demonstrating a significant association with weight or age were
      excluded, IL-6 (p=0.016) and G-CSF (p=0.024) were found to correlate positively
      with total histological score. Models involving each of these cytokines paired
      independently with weight explained 43-44% of the variance in total histology.
      CONCLUSIONS: Only the age and weight-independent associations of IL-6 and G-CSF
      with histological OA were significant under the conditions imposed by the Holm
      step-down adjustment for multiple comparisons. Though the observed changes of
      these cytokine levels may be due to a correlation with age, it is highly unlikely
      given the significant difference between Hartley and Strain 13 age-matched
      cohorts.

PMID- 17208468
TI  - Human umbilical cord blood serum can replace fetal bovine serum in the culture of
      mesenchymal stem cells.
AB  - The potential of mesenchymal stem cells (MSC) to differentiate into different
      cell types has opened up the possibility of using these cells clinically to treat
      a variety of disorders. In this study we describe the use of human umbilical cord
      blood serum (CBS) as a replacement for fetal bovine serum (FBS) for culturing MSC
      from different sources. MSC from human and swine bone marrow and human umbilical
      cord blood were cultured in the presence of DMEM/F12 containing either FBS or
      CBS. Human MSC cultured in presence of FBS or CBS showed typical fibroblast-like
      morphology, which is characteristic of MSC. 99% of the cells cultured in FBS had
      a CD73+/CD105+/CD45- phenotype compared to 96% of cells cultured in CBS. Cells
      cultured in CBS had a significantly higher cell count as compared to cells
      cultured in FBS. Swine Bone Marrow MSC cultured in the presence of FBS and CBS
      were morphologically and phenotypically similar. Human umbilical cord blood serum
      supports the growth of MSC. While no significant differences were observed in the
      MSC numbers in swine cells cultured in the presence of FBS or CBS, human cells
      showed a greater proliferation potential in the presence of CBS as compared to
      FBS. Therefore, CBS can be used as an effective substitute to FBS for developing
      clinically useful protocols for culturing MSC.

PMID- 17208469
TI  - Histological evaluation of contaminated furcal perforation in dogs' teeth
      repaired by MTA with or without internal matrix.

PMID- 17208470
TI  - Nucleic acids with a six-membered carbohydrate mimic and RNA interference.
AB  - Cyclohexenyl nucleic acids and altritol nucleic acids were evaluated as RNA
      modifications in an siRNA experiment targeting the P-glycoprotein expression.
      Both modified oligonucleotides are well accepted as RNA mimics leading to an
      increase in potency and duration of action of the gene-silencing effect.

PMID- 17208471
TI  - Physiologically important secondary modifications of red cell membrane in
      hereditary spherocytosis-evidence for in vivo oxidation and lipid rafts protein
      variations.
AB  - Hereditary spherocytosis (HS) is a heterogeneous group of disorders. The abnormal
      red cell morphology (resulting in shortened cell survival) is due to a primary
      deficiency in spectrin, ankyrin-1, band 3 or protein 4.2. Secondary protein
      deficiencies are often observed and may be involved in the outcome of the
      disease. In the present study, we searched for secondary erythrocyte membrane
      protein alterations in HS, including the lipid raft associated proteins and the
      oxidative index. For this purpose, 12 patients with clinical and laboratory
      diagnosis of mild to typical HS were examined. Erythrocyte membrane ghosts and
      skeletons were subjected to SDS-PAGE and immunoblotting analysis using antibodies
      against red cell membrane proteins and DNP moiety, after 2,4
      dinitrophenylhydrazine derivatization. Protein deficiencies, degradation,
      aggregation and enhanced binding of cytoplasmic components, band 8, hemoglobin
      and immunoglobulins G to the membrane as well as increased oxidative index, were
      found in the majority of the HS patients. Proportion of the membrane- and
      skeleton-bound globin was oxidized/denatured Hb or hemichromes and crosslinkings.
      Some HS membranes are deficient in lipid rafts proteins and contain sorcin. A
      context of these distortions is more pronounced in typical HS cases compared to
      the mild ones. Similar defects in thalassemia and senescent RBCs are dictated by
      increased oxidative stress and are positively correlated with perturbations in
      membrane properties. These data add some new insight in the field of HS
      pathophysiology and clinical variability.

PMID- 17208472
TI  - Heart development in Drosophila.
AB  - The Drosophila heart, also called the dorsal vessel, is an organ for hemolymph
      circulation that resembles the vertebrate heart at its transient linear tube
      stage. Dorsal vessel morphogenesis shares several similarities with early events
      of vertebrate heart development and has proven to be an insightful system for the
      study of cardiogenesis due to its relatively simple structure and the productive
      use of Drosophila genetic approaches. In this review, we summarize published
      findings on Drosophila heart development in terms of the regulators and genetic
      pathways required for cardiac cell specification and differentiation, and organ
      formation and function. Emerging genome-based strategies should further
      facilitate the use of Drosophila as an advantageous system in which to identify
      previously unknown genes and regulatory networks essential for normal cardiac
      development and function.

PMID- 17208473
TI  - Factors that predispose, prime and precipitate NREM parasomnias in adults:
      clinical and forensic implications.
AB  - Sleepwalking and related disorders are the result of factors that predispose,
      prime and precipitate episodes. In the absence of one or more of these factors
      sleepwalking is unlikely to occur. Predisposition to sleepwalking is based on
      genetic susceptibility and has a familial pattern. Priming factors include
      conditions and substances that increase slow wave sleep (SWS) or make arousal
      from sleep more difficult. These factors include sleep deprivation, alcohol,
      medications, situational stress and fever among others. The patient with a
      genetic predisposition to sleepwalking and with priming factors still requires a
      precipitating factor or trigger to set the sleepwalking episode in motion.
      Classical theories of sleepwalking were based primarily on case reports. Recently
      some of these theories have been tested in the sleep laboratory. Experimental
      sleep deprivation studies of sleepwalkers generally report an increase in complex
      behaviors during SWS, although one prominent study reported the opposite effect.
      However, the generally accepted theory that alcohol and medications can induce
      sleepwalking episodes remains entirely based on clinical and forensic case
      reports. Alleged cases of alcohol related sleepwalking often involve individuals
      lacking the generally accepted characteristics of sleepwalkers but with very high
      blood alcohol levels that could in and of itself account for complex behaviors
      noted without the presence of sleepwalking. Further, the effects of high levels
      of alcohol dramatically decrease SWS, a finding inconsistent with sleepwalking.
      Case reports of medication-related induction of apparent sleepwalking most often
      present a complex medical and psychiatric history associated with multiple
      medications. These patients often lack the clinical history and other criteria
      currently required for the diagnosis of sleepwalking. The medication-related
      behaviors may instead represent some other condition in an awake, but impaired
      patient. Sleep laboratory research has identified sleep disordered breathing,
      periodic leg movements, noise and touch among others as proximal triggers of
      sleepwalking episodes. Treatment of these triggers may result in resolution of
      sleepwalking without medication. Further sleep laboratory research is needed
      before experimental findings can be used for routine diagnostic and forensic
      purposes.

PMID- 17208474
TI  - Differential activation of macrophages in vitro by lectin Concanavalin A,
      Phytohemagglutinin and Wheat germ agglutinin: production and regulation of nitric
      oxide.
AB  - The role of Concanavalin A (ConA), Phytohemagglutinin (PHA) and Wheat germ
      agglutinin (WGA) in the activation of murine peritoneal macrophages particularly
      with reference to production and regulation of nitric oxide (NO) has been
      investigated. Macrophages on treatment with ConA and PHA showed significantly
      enhanced production of NO, which was dose and time dependent. On the other hand
      macrophages treated with WGA did not produce NO. L-N-monomethyal-l-arginine (L
      NMMA), an inhibitor of NOS inhibited the ConA and PHA induced NO production. ConA
      and PHA treatment of macrophages induced transcription of iNOS gene and the
      enhanced expression of iNOS protein. Pharmacological inhibitors of PI3 kinase
      Wortmannin, tyrosine kinase-Genestein, protein kinase C-H-7 and p42/44-PD98059
      inhibited the ConA and PHA induced production of NO and p38 MAP kinase inhibitor
      SB202190 inhibited NO production only in ConA treated macrophage, while Galphai
      protein inhibitor-PTX and JNK inhibitor-SP600125 inhibited NO production in PHA
      treated macrophages. Tyrophostin (AG490), an inhibitor of JAK2 and TMB-8, an
      intracellular calcium immobilizing agent also inhibited the ConA and PHA induced
      NO production, suggesting the involvement of JAK-STAT pathway and calcium. The
      data also provides the relative measure and importance of different key signaling
      molecules in the regulation of NO production by macrophages on activation.

PMID- 17208475
TI  - Induction of dendritic cell-mediated immune responses against canine malignant
      melanoma cells.
AB  - To establish the basis for the use of dendritic cells (DC) in the treatment of
      canine melanoma, dogs were vaccinated using autologous DC pulsed with canine
      melanoma CMM2 cell lysate in the presence of keyhole limpet haemocyanin (KLH) in
      vitro (CMM2-KLH-DC), and the induction of immune responses against CMM2 cells in
      vivo was examined using the delayed-type hypersensitivity (DTH) skin test. The
      DTH responses against CMM2 cells and KLH were observed in dogs vaccinated with
      CMM2-KLH-DC, while the responses against KLH but not CMM2 cells were detected
      with DC pulsed with KLH alone (KLH-DC). Recruitment of CD8 and CD4 T cells was
      detected in the positively responding sites, suggested that vaccination with CMM2
      KLH-DC efficiently elicits T cell-mediated immunity against CMM-2 cells in vivo.
      These findings demonstrate the potential utility of DC-based tumour vaccination
      in the treatment of canine malignant melanoma.

PMID- 17208476
TI  - Detection of NMR signals with a radio-frequency atomic magnetometer.
AB  - We demonstrate detection of proton NMR signals with a radio-frequency (rf) atomic
      magnetometer tuned to the NMR frequency of 62 kHz. High-frequency operation of
      the atomic magnetometer makes it relatively insensitive to ambient magnetic field
      noise. We obtain magnetic field sensitivity of 7 fT/Hz1/2 using only a thin
      aluminum shield. We also derive an expression for the fundamental sensitivity
      limit of a surface inductive pick-up coil as a function of frequency and find
      that an atomic rf magnetometer is intrinsically more sensitive than a coil of
      comparable size for frequencies below about 50 MHz.

PMID- 17208478
TI  - Ovarian development and plasma sex steroid levels in cultured female Senegalese
      sole Solea senegalensis.
AB  - Ovarian development was studied in cultured female Senegalese sole Solea
      senegalensis. Females with regressed ovaries, mainly occupied by perinucleolar
      oocytes, predominated throughout summer exhibiting low condition factor (K),
      gonadosomatic index (I(G)), and plasma 17beta-estradiol and testosterone levels.
      Throughout autumn and winter (ovaries at early and intermediate maturation),
      oocytes progressed to cortical alveoli and vitellogenic stages accompanied by
      increasing K, I(G), and plasma 17beta-estradiol and testosterone levels. At late
      winter/early spring, ovarian development reached its maximum with the
      predominance of females at intermediate and final maturation (the latter occupied
      by late vitellogenic oocytes and few early maturation oocytes) and peak values of
      K, I(G), and 17beta-estradiol and testosterone concentrations. Steroid levels
      were lower (especially testosterone) than those for naturally-spawning females,
      which might cause extensive atresia without final oocyte maturation (no spawning
      was observed). This degenerative process reduced de size of the ovary (initial
      and intermediate phases of regression) in association with declining K, I(G), and
      plasma 17beta-estradiol and testosterone levels and increasing proportions of
      perinucleolar oocytes. The circulating 17,20beta-dihydroxy-4-pregnen-3-one
      levels, the proposed maturation-inducing steroid, remained relatively constant
      throughout the experimental period, suggesting that oocytes were unable to
      respond adequately to its stimulation. We propose the inadequate seasonal thermal
      regime as the main cause of such dysfunction.

PMID- 17208477
TI  - Corticosterone stimulates hatching of late-term tree lizard embryos.
AB  - The regulation of hatching in oviparous animals is important for successful
      reproduction and survival, but is poorly understood. We unexpectedly found that
      RU-486, a progesterone and glucocorticoid antagonist, interferes with hatching of
      viable tree lizard (Urosaurus ornatus) embryos in a dose-dependent manner and
      hypothesized that embryonic glucocorticoids regulate hatching. To test this
      hypothesis, we treated eggs with corticosterone (CORT) or vehicle on Day 30 (85%)
      of incubation, left other eggs untreated, and observed relative hatch order and
      hatch time. In one study, the CORT egg hatched first in 9 of 11 clutches. In a
      second study, the CORT egg hatched first in 9 of 12 clutches, before vehicle
      treated eggs in 10 of 12 clutches, and before untreated eggs in 7 of 9 clutches.
      On average, CORT eggs hatched 18.2 h before vehicle-treated eggs and 11.6 h
      before untreated eggs. Thus, CORT accelerates hatching of near-term embryos and
      RU-486 appears to block this effect. CORT may mobilize energy substrates that
      fuel hatching and/or accelerate lung development, and may provide a mechanism by
      which stressed embryos escape environmental stressors.

PMID- 17208479
TI  - Non-enzymatic lipid peroxidation of microsomes and mitochondria from liver, heart
      and brain of the bird Lonchura striata: relationship with fatty acid composition.
AB  - The aim of this study was to examine the fatty acid composition and non-enzymatic
      lipid peroxidation (LP) of mitochondria and microsomes obtained from liver, heart
      and brain of Lonchura striata. The percentage of total unsaturated fatty acid was
      approximately 30-60% in the organelles from all tissues studied. Brain
      mitochondria and both organelles of liver exhibited the highest percentage of
      polyunsaturated fatty acid (PUFA) (30 and 18%, respectively). The arachidonic
      acid (AA) content was 7% in mitochondria of liver and brain and 3% in heart
      mitochondria. The percentage of docosahexanoic acid (DHA) was 8% in brain
      mitochondria and approximately 2-3% in heart and liver mitochondria. The
      peroxidizability index (PI) of brain mitochondria and both organelles from liver
      was higher than that of organelles from heart and brain microsomes. Liver
      organelles and brain mitochondria were affected by LP, as indicated by the
      increase in chemiluminescence and a decrease of AA and DHA. These changes were
      not observed during LP of brain microsomes and both organelles from heart. These
      results indicate: 1) PI positively correlates with PUFA percentage and LP; 2) The
      resistance to LP detected in heart organelles would contribute to the cardiac
      protection against oxidative damage.

PMID- 17208480
TI  - Chemical composition, mineral content and amino acid and lipid profiles in bones
      from various fish species.
AB  - The chemical composition, content of minerals and the profiles of amino acids and
      fatty acids were analyzed in fish bones from eight different species of fish.
      Fish bones varied significantly in chemical composition. The main difference was
      lipid content ranging from 23 g/kg in cod (Gadus morhua) to 509 g/kg in mackerel
      (Scomber scombrus). In general fatty fish species showed higher lipid levels in
      the bones compared to lean fish species. Similarly, lower levels of protein and
      ash were observed in bones from fatty fish species. Protein levels differed from
      363 g/kg lipid free dry matter (dm) to 568 g/kg lipid free dm with a concomitant
      inverse difference in ash content. Ash to protein ratio differed from 0.78 to
      1.71 with the lowest level in fish that naturally have highest swimming and
      physical activity. Saithe (Pollachius virens) and salmon (Salmo salar) were found
      to be significantly different in the levels of lipid, protein and ash, and
      ash/protein ratio in the bones. Only small differences were observed in the level
      of amino acids although species specific differences were observed. The levels of
      Ca and P in lipid free fish bones were about the same in all species analyzed.
      Fatty acid profile differed in relation to total lipid levels in the fish bones,
      but some minor differences between fish species were observed.

PMID- 17208481
TI  - Characterization of Inhibitor of Growth 2 tumor suppressor in Alligator
      mississippiensis, its conservation in Archosauria, and response to thyroid
      stimulating hormone.
AB  - Inhibitor of growth 2 (ING2) belongs to a family of tumor suppressors that are
      important regulators of a wide range of cellular processes including
      proliferation, apoptosis, and DNA repair. ING family members are found in yeast,
      plants, invertebrates and many vertebrate species. However, to date, ING has not
      been characterized in reptiles. Herein we describe the isolation of expressed
      ING2 sequence in the American alligator, Alligator mississippiensis, and compare
      this sequence with that isolated in the chicken. We identify features that are
      unique to these two representatives of the Archosaurs including conservation of
      specific amino acid residues and the absence of an adenylate residue in the 5'
      end of the nucleotide sequence relative to frogs and mammals. The latter feature
      results in an alteration of the coding potential leading to distinctive N
      termini. Injection of juvenile alligators with thyroid stimulating hormone (TSH),
      which increases endogenous thyroid hormones, results in the modulation of ING2
      transcript levels. Quantitative real time polymerase chain reaction analyses
      revealed a reduction in the steady-state levels of ING2 mRNA in the
      phallus/cliterophallus, lung, and liver by 48 h after TSH injection. ING2
      expression in the thyroid gland, gonad, and heart was unaffected by TSH
      treatment. These data indicate that control of ING2 expression by the thyroid
      axis may be conserved among species and is tissue-dependent.

PMID- 17208482
TI  - Changes in cholecystokinin and peptide Y gene expression with feeding in
      yellowtail (Seriola quinqueradiata): relation to pancreatic exocrine regulation.
AB  - In fish, the regulation of digestive enzyme secretion by hormonal control such as
      cholecystokinin (CCK) and neuropeptide Y (NPY)-related peptide is not well
      understood. To investigate the roles of fish CCK and peptide Y (PY) in digestive
      enzyme secretion, mRNA levels of CCK and PY, pyloric caeca enzyme activities and
      mRNA levels of pancreatic digestive enzymes (lipase, trypsin and amylase) were
      measured at pre- and post-prandial stages in yellowtail. Pyloric caeca were
      sampled at 0, 0.5, 1.5, 3, 6, 12, 24 and 48 h after feeding. The mRNA levels of
      trypsin and amylase increased after feeding, suggesting that transcription was
      induced by feed ingestion. Digestive enzyme activities decreased in exocrine
      pancreas after feeding, suggesting the stored enzyme was secreted from pancreas
      post-prandially. mRNA levels for CCK displayed a time-dependent increase, peaking
      between 1.5 and 3 h after-feeding followed by a rapid decrease 3 to 6 h after
      feeding. The mRNA expression pattern of PY was inverse to the pattern of CCK,
      decreasing until 1.5 h after feeding and then rising to initial levels by 12 h
      after feeding. These results suggest that CCK and PY work antagonistically in the
      exocrine pancreas of yellowtail.

PMID- 17208483
TI  - Free insulin-like growth factor-I and cognitive function in older persons living
      in community.
AB  - CONTEXT: Increasing evidences from experimental and human studies suggest that
      the activity of the growth hormone (GH/insulin-like growth factor-I) axis may
      contribute to the age-related cognitive decline and poor cognition in late life.
      OBJECTIVE: The aim of the present study was to evaluate the relationship of total
      serum free IGF-I and its binding protein-3 with cognitive performance in older
      persons aged 80 years or older. DESIGN: Data are from baseline evaluation of the
      ilSIRENTE study (n=353). Cognitive performance was evaluated using five items
      enclosed in the Minimum Data Set for Home Care assessment form: short-term
      memory, procedural memory, cognitive skills in daily decision making, verbal
      expression, comprehension. Free insulin-like growth factor-I (free IGF-I) and IGF
      binding protein-3 (IGFBP-3) in blood were measured. Analysis of covariance
      (ANCOVA) was used to examine the relationship between cognitive impairment and
      the serum free IGF-I and IGFBP-3 concentrations, after adjustment for potential
      confounding variables. RESULTS: After adjustment for potential confounders, which
      included age, gender, education, cerebrovascular disease, ischemic heart disease,
      congestive heart failure, hypertension, diabetes, depression, Parkinson diseases,
      thyroid diseases, smoking status, alcohol abuse, body mass index, and number of
      medications, individuals with verbal expression problems (n=20) and individuals
      with comprehension problems (n=24) had a significantly lower serum levels of
      readily dissociable IGF-I than participants without cognitive impairments. The
      serum IGFBP-3 presented the same behavior of free IGF-I. CONCLUSION: The present
      study suggests that among old-old subjects living in the community lower levels
      of total serum free IGF-I and IGFBP-3 are associated with impairment of cognitive
      performance. This finding suggests that the GH/IGF-I axis may play an important
      role in the age-related decline of cognitive performance.

PMID- 17208484
TI  - Relationships between BK virus lineages and human populations.
AB  - BK polyomavirus (BKV) is ubiquitous in human populations, infecting children
      asymptomatically and then persisting in the kidney, in which it can cause
      nephropathy in renal transplant patients. BKV isolates are classified into four
      subtypes (I-IV) using serological or genotyping methods, and subtype I is further
      divided into four subgroups, Ia, Ib-1, Ib-2, and Ic, based on DNA sequence
      variations. To clarify whether there is an association between BK virus lineages
      and human populations, we examined BKV-positive urine samples collected from
      immunocompetent individuals at various locations in Europe, Africa, and Asia.
      Partial BKV DNA sequences (n=299) in these samples were determined and subjected
      to phylogenetic and single nucleotide polymorphism analysis to classify BKV
      isolates around the world. The validity of the classification was confirmed by
      analyses based on complete BKV DNA sequences. Subtype I was the major subtype
      throughout the studied regions, and subtype IV was prevalent only in Asia and
      Europe. Subtype-I subgroups showed close relationships to major geographical
      areas. It has recently been shown that JC virus (a human polyomavirus closely
      related to BKV) co-evolved with human populations, and the present study thus
      suggests that host-linked evolution is the general mode of polyomavirus
      evolution. Additionally, our results indicate certain unique aspects of the
      relationship between BKV and humans.

PMID- 17208485
TI  - Pathogenesis of cytomegalovirus-associated labyrinthitis in a guinea pig model.
AB  - Cytomegalovirus infects fetuses through the placenta, resulting in various
      congenital disorders in newborns, including hearing loss. We developed a
      monoclonal antibody to guinea pig cytomegalovirus (GPCMV) that was available for
      immunohistochemistry, and investigated the expression of the GPCMV antigen in
      animal models of direct and congenital infections. Injection of GPCMV, directly
      to the inner ear, increased the sound pressure level and resulted in
      labyrinthitis with severe inflammation. Immunohistochemistry detected GPCMV
      infected cells mainly in the scala tympani, scala vestibule and spinal ganglion,
      but rarely in the cochlear duct. Injection of GPCMV to 5-week pregnant guinea
      pigs resulted in severe labyrinthitis in fetuses. Immunohistochemistry detected
      GPCMV-infected cells in the perilymph area and spinal ganglion, but not in the
      endolymph area, including hair cells. These data suggest that the virus spreads
      via the perilymph and neural routes in the inner ear of both models of direct and
      congenital infections.

PMID- 17208486
TI  - Caenorhabditis elegans as a simple model to study phenotypic and genetic
      virulence determinants of extraintestinal pathogenic Escherichia coli.
AB  - Extraintestinal pathogenic Escherichia coli (ExPEC) strains cause disease by
      invading normally sterile niches within the host body, e.g., urinary tract, blood
      and cerebrospinal fluid. Infections due to ExPEC strains, in particular urinary
      tract infections, cause considerable morbidity and significant health-care costs.
      The goal of our study is to evaluate whether Caenorhabditis elegans can be used
      as a model to study phenotypic and genetic virulence determinants of ExPEC
      strains. For this purpose, we used a collection of 31 E. coli strains isolated
      during acute extra-intestinal infections or from the feces of healthy
      individuals. For all strains, the phylogeny, the presence of ExPEC virulence
      factors, the resistance to biologically relevant stressors (bile, human serum and
      lysozyme), the motility, the growth rate, the virulence in C. elegans and in a
      murine septicaemia model has been established. The results show that there is a
      strong link between virulence in C. elegans and certain phenotypic and genetic
      virulence predictors of ExPEC strains determinable in vitro. Furthermore, there
      is a significant correlation between virulence of different ExPEC strains in C.
      elegans and in the murine model. Therefore, our results suggest that C. elegans
      can be used as a model to study virulence determinants of ExPEC strains.

PMID- 17208487
TI  - Association analyses of NCR3 polymorphisms with P. falciparum mild malaria.
AB  - Plasmodium falciparum malaria is a major cause of morbidity and mortality in many
      developing countries especially in sub-Saharan Africa. A susceptibility locus for
      mild malaria has been mapped to the MHC region, and TNF polymorphisms have been
      associated with mild malaria. The Natural Cytotoxicity-triggering Receptor 3
      (NCR3) gene is located in the peak region of linkage, and is 15kb distal to TNF.
      In this study, we considered NCR3 as a candidate gene, and we genotyped ten NCR3
      single nucleotide polymorphisms (SNPs). Here, we report evidence of an
      association between mild malaria and NCR3 -412G>C polymorphism located within the
      promoter. Population-based association analysis showed that NCR3 -412C carriers
      had more frequent mild malaria attacks than NCR3 -412GG individuals (P=0.001).
      Using the family-based association test (FBAT) program and its phenotype (PBAT)
      option, we further found that NCR3 -412C (P=0.0009) and a haplotype containing
      NCR3 -412C (P=0.008) were significantly associated with increased risk of mild
      malaria, and that the association was not due to the association of TNF with mild
      malaria. These observations suggest that there are at least two genes located on
      the central region of MHC involved in genetic control of human malaria. The
      association of NCR3 with malaria should provide new insights into the role of
      Natural Killer cells in this common disease.

PMID- 17208488
TI  - Mycobacterium smegmatis produces an HBHA homologue which is not involved in
      epithelial adherence.
AB  - Mycobacterium tuberculosis produces heparin-binding hemagglutinin (TB-HBHA), an
      adhesin involved in binding to non-professional phagocytes and in extrapulmonary
      dissemination. TB-HBHA binds sulphated glycoconjugates through its C-terminal
      lysine-rich domain and can be purified by heparin-Sepharose chromatography.
      Homologues of HBHA are found in other pathogenic mycobacteria, but previous
      investigations failed to demonstrate them in non-pathogenic Mycobacterium
      smegmatis. We identified a gene encoding a HBHA-like protein, named MS-HBHA, from
      the complete M. smegmatis genome. The deduced MS-HBHA amino acid sequence
      revealed 68% identity with that of TB-HBHA and contains lysine-rich repeats in
      its C-terminal domain. However, in contrast to TB-HBHA, the lysine-rich domain of
      MS-HBHA is preceded by a stretch of acidic residues. This difference likely
      explains the low affinity for heparin displayed by MS-HBHA compared to TB-HBHA.
      Isolation by heparin-Sepharose chromatography procedure and mass spectrometry
      analysis indicated that MS-HBHA, similar to TB-HBHA contains several methylated
      lysine residues in its C-terminal domain. Although MS-HBHA is associated with M.
      smegmatis cell wall fractions, it does not seem to play a role in epithelial
      adherence and its function remains unknown. We therefore conclude that TB-HBHA
      may have evolved as an adhesin in pathogenic mycobacteria from a homolog that
      serves a different function in a saprophytic mycobacterium.

PMID- 17208489
TI  - Role of GPI-anchored NCAM-120 in rabies virus infection.
AB  - Although the neural cell adhesion molecule (NCAM) -140 and -180 have been shown
      to serve as a receptor for rabies virus (RV), it was not known whether the other
      major isoform of NCAM, GPI-anchored NCAM-120 functions as RV receptor. In this
      study, we have established HEp-2 cells stably expressing NCAM-120 or NCAM-140,
      and their susceptibilities to RV infection were compared. The results
      demonstrated that NCAM-120 served as virus attachment protein; however, the cells
      expressing NCAM-120 did not support efficient RV replication. Furthermore, the
      level of IFN-ss mRNA was apparently elevated in NCAM-120 expressing cells but not
      in NCAM-140 expressing cells, suggesting that GPI-anchored NCAM-120 suppressed RV
      replication via induction of IFN-ss even though NCAM-120 was able to promote
      virus penetration into the cells.

PMID- 17208490
TI  - [How I perform...to estimate the engagement of the foetal head].

PMID- 17208491
TI  - [Laparoscopic surgery of deep endometriosis. About 118 cases].

PMID- 17208492
TI  - [In favour of a conservative medical treatment of ectopic pregnancies].

PMID- 17208493
TI  - [Hematocolpos due to obstructed hemivagina. About three cases].

PMID- 17208494
TI  - [Treating severe endometriosis by pregnancy: a risky business].
AB  - We report the case of a young woman presenting with painful deep and rectal
      endometriosis. This condition had started long ago while the diagnosis had been
      delayed. Brutal colon occlusion followed the discontinuation of oral
      contraception. Left colectomy with terminal colostomy was carried out in
      emergency. The conservative surgical management of deep endometriosis was
      performed three months later. In women presenting deep endometriosis, the
      discontinuation of hormonal treatment in order to attempt a spontaneous pregnancy
      should not be recommended before undertaking a thorough endometriosis and
      fertility status investigation.

PMID- 17208495
TI  - [Laparoscopic surgery of deep endometriosis. About 118 cases].

PMID- 17208496
TI  - [Are French results in assisted reproductive techniques so bad?].
AB  - OBJECTIVE: Comparative analysis of French results in Assisted Reproductive
      Techniques (ART) versus those from other European countries and the United
      States. POPULATION AND METHODS: The study was achieved by using the officially
      available data. The analysis was faced with a lot of difficulties in relation
      with the various methods of collecting data in the different countries. RESULTS:
      Nevertheless, it appears clearly that French results are among the lowest in
      Europe with a 22% rate for pregnancy per ovum pick-up with IVF and 23.4% with
      ICSI, when most of the other countries report rates that are close to or over
      30%. Neither the patients' pick-up recruitment nor specific practices of ART can
      explain this difference that certainly comes from a deficient quality of the
      French IVF centres. DISCUSSION AND CONCLUSION: We think that four main end-points
      can explain this situation: the lack of financial support, the lack of human
      force, the lack of transparency and finally the opposition between clinician and
      biologist that has blocked the set-up of integrated ART centres, and probably a
      poor quality culture.

PMID- 17208497
TI  - [Forceps delivery or vacuum extraction: no, forceps AND vacuum extraction!].

PMID- 17208499
TI  - [Forceps delivery or vacuum extraction: no, forceps AND vacuum extraction!].

PMID- 17208500
TI  - Doping nanoparticles into polymers and ceramics using ultrasound radiation.
AB  - In materials science, sonochemistry is mostly used for the fabrication of
      nanomaterials, but it has also been used for the polymerization of monomers. The
      current review is aimed at introducing a new application of sonochemistry to
      materials science, i.e., the doping of nanoparticles into polymers and ceramic
      bodies. The introduction will present a short overview of sonochemistry, and will
      outline the advantages of sonochemistry as a tool for fabricating nanomaterials.

PMID- 17208501
TI  - Numerical simulations of the aspherical collapse of laser and acoustically
      generated bubbles.
AB  - The details of nonlinear axisymmetric oscillations and collapse of bubbles
      subject to large internal or external pressure disturbances, are studied via a
      boundary integral method. Weak viscous effects on the liquid side are accounted
      for by integrating the equations of motion across the boundary layer that is
      formed adjacent to the interface. Simulations of single-cavitation bubble
      luminescence (SCBL) and single-bubble sonoluminescence (SBSL) are performed under
      conditions similar to reported experimental observations, aiming at capturing the
      details of bubble collapse. It is shown that any small initial deviation from
      sphericity, modeled through a small initial elongation along the axis of
      symmetry, may result in the formation and impact of two counter-propagating jets
      during collapse of the bubble, provided the amplitude of the initial disturbance
      is large enough and the viscosity of the surrounding fluid is small enough.
      Comparison between simulations and experimental observations show that this is
      the case for bubbles induced via a nano-second laser pulse (SCBL) during a
      luminescence event. In a similar fashion, simulations show that loss of
      sphericity accompanied with jet formation and impact during collapse is also
      possible with acoustically trapped bubbles in a standing pressure wave (SBSL),
      due to the many afterbounces of the bubble during its collapse phase. In both
      cases jet impact occurs as a result of P(2) growth in the form of an afterbounce
      instability. When the sound amplitude is decreased or liquid viscosity is
      increased the intensity of the afterbounce is decreased and jet impact is
      suppressed. When the sound amplitude is increased jet formation is superceded by
      Rayleigh-Taylor instability. In the same context stable luminescence is quenched
      in experimental observations. In both SCBL and SBSL simulations the severity of
      jet impact during collapse is quite large, and its local nature quite distinct.
      This attests to the fact that it is an energy focusing mechanism whose importance
      in generating the conditions under which a luminescence event is observed should
      be further investigated.

PMID- 17208503
TI  - Electrosynthesis of hydrogen peroxide via the reduction of oxygen assisted by
      power ultrasound.
AB  - The electrosynthesis of hydrogen peroxide using the oxygen reduction reaction has
      been studied in the absence and presence of power ultrasound in a non-optimized
      sono-electrochemical flow reactor (20 cm cathodic compartment length with 6.5 cm
      inner diameter) with reticulated vitreous glassy carbon electrode (30 x 40 x 10
      mm, 10 ppi, 7 cm(2)cm(-3)) as the cathode. The effect of several electrochemical
      operational variables (pH, volumetric flow, potential) and of the sono
      electrochemical parameters (ultrasound amplitude and horn-to-electrode distance)
      on the cumulative concentration of hydrogen peroxide and current efficiency of
      the electrosynthesis process have been explored. The application of power
      ultrasound was found to increase both the cumulative concentration of hydrogen
      peroxide and the current efficiency. The application of ultrasound is therefore a
      promising approach to the increased efficiency of production of hydrogen peroxide
      by electrosynthesis, even in the solutions of lower pH (<12). The results
      demonstrate the feasibility of at-site-of-use green synthesis of hydrogen
      peroxide.

PMID- 17208504
TI  - Characterization and activity of sonochemically-prepared BSA microspheres
      containing Taxol--an anticancer drug.
AB  - Proteinaceous microspheres of BSA (Bovine Serum Albumin) containing an anticancer
      drug, Taxol (paclitaxel) were fabricated using a sonochemical procedure and then
      assayed for chemical and biological activity. The sonochemical reaction did not
      compromise the drug, which became encapsulated in the BSA microspheres. The
      amount of the anticancer drug in the microspheres was determined by HPLC.
      Anticancer activity of the proteinaceous microspheres encapsulating the Taxol was
      tested on Mouse Multiple Myeloma cell line MPC-11. The influence of the Taxol
      microspheres on the cancer cells was different from pristine Taxol. It was found
      that Taxol in combination with the organic solvent causes the death of cancer
      cells.

PMID- 17208505
TI  - Mixture segregation by an inertial cavitation bubble.
AB  - Pressure diffusion is a mass diffusion process forced by pressure gradients. It
      has the ability to segregate two species of a mixture, driving the densest
      species toward high pressure zones, but requires very large pressure gradients to
      become noticeable. An inertial cavitation bubble develops large pressure
      gradients in its vicinity, especially as the bubble rebounds at the end of its
      collapse, and it is therefore expected that a liquid mixture surrounding such a
      bubble would become segregated. Theory developed in an earlier paper shows that
      this is indeed the case for sufficiently large molecules or nano-particles. The
      main theoretical results are recalled and a possible implication of this
      segregation phenomenon on the well-known cavitation-enhanced crystals nucleation
      is proposed.

PMID- 17208506
TI  - Iliotibial band friction syndrome--a systematic review.
AB  - Iliotibial band friction syndrome (ITBFS) is a common injury of the lateral
      aspect of the knee particularly in runners, cyclists and endurance sports. A
      number of authors suggest that ITBFS responds well to conservative treatment,
      however, much of this opinion appears anecdotal and not supported by evidence
      within the literature. The purpose of this paper is to provide a systematic
      review of the literature pertaining to the conservative treatment of ITBFS. A
      search to identify clinical papers referring to the iliotibial band (ITB) and
      ITBFS was conducted in a number of electronic databases using the keyword:
      iliotibial. The titles and abstracts of these papers were reviewed to identify
      papers specifically detailing conservative treatments of ITBFS. The PEDro Scale,
      a systematic tool used to critique randomized controlled trials (RCTs), was
      employed to investigate both the therapeutic effect of conservative treatment of
      ITBFS and also to critique the methodological quality of available RCTs examining
      the conservative treatment of ITBFS. With respect to the management of ITBFS,
      four RCTs were identified. The interventions examined included the use of non
      steroidal anti-inflammatory drugs (NSAIDs), deep friction massage, phonophoresis
      versus immobilization and corticosteroid injection. This review highlights both
      the paucity in quantity and quality of research regarding the conservative
      treatment of ITBFS. There seems limited evidence to suggest that the conservative
      treatments that have been studied offer any significant benefit in the management
      of ITBFS. Future research will need to re-examine those conservative therapies,
      which have already been examined, along with others, and will need to be of
      sufficient quality to enable accurate clinical judgements to be made regarding
      their use.

PMID- 17208507
TI  - Sphincter incontinence: is regenerative medicine the best alternative to restore
      urinary or anal sphincter function?
AB  - Incontinence is a major public health concern in aging societies. It is caused by
      age-dependent spontaneous apoptosis of muscle cells in the urinary and fecal
      sphincters, and is aggravated in women due to birth trauma. Compared to other
      currently employed invasive surgical management techniques associated with
      morbidity and recurrence, replacement or regeneration of dysfunctional sphincter
      through stem cell therapy and tissue engineering techniques hold great promise.
      This review focuses on the pathophysiological analysis of urinary incontinence
      and the possible application of muscle-derived-stem cells, satellite cells,
      chondrocytes and adipose-derived-stem cells in restoring sphincter functions.

PMID- 17208508
TI  - Submergence tolerance in rice requires Sub1A, an ethylene-response-factor-like
      gene.
AB  - Submergence of rice (Oryza sativa) by flash flooding is a major constraint to
      rice production in Asia. Rice cultivars vary in their capacity to tolerate
      complete submergence; quantitative trait loci analyses have revealed that a large
      portion of this variation in submergence tolerance can be explained by one locus
      (Sub1) on chromosome 9. Two recently published papers (Takeshi Fukao et al. and
      Kenong Xu et al.) present evidence that a transcription factor belonging to the B
      2 subgroup of the ethylene response factors (ERFs)/ethylene-responsive element
      binding proteins (EREBPs)/apetala 2-like proteins (AP2) within the Sub1 locus
      determines submergence tolerance in rice. These genes control highly conserved
      hormonal, physiological and developmental processes that determine the rate of
      elongation when submerged.

PMID- 17208509
TI  - Methyl-CpG-binding domain proteins in plants: interpreters of DNA methylation.
AB  - The effect of DNA methylation on various aspects of plant cellular and
      developmental processes has been well documented over the past 35 years. However,
      the underlying molecular mechanism interpreting the methylation signal has only
      recently been explored with the isolation and characterization of the Arabidopsis
      methyl-CpG-binding domain (MBD) proteins. In this review, we highlight recent
      advances and present new models concerning Arabidopsis MBD proteins and their
      possible role in controlling chromatin structure mediated by CpG methylation.

PMID- 17208510
TI  - Phylloplane proteins: emerging defenses at the aerial frontline?
AB  - The phylloplane, or leaf surface, is an interkingdom crossroads between plants
      and microorganisms, and secretion of antimicrobial biochemicals to aerial
      surfaces is thought to be one defensive strategy by which plants deter potential
      pathogens. Secondary metabolites on leaf surfaces are well documented but
      antimicrobial phylloplane proteins have only recently been identified. In this
      review, we describe the physical structures and biochemicals of the phylloplane
      and briefly discuss protein-based surface defenses of animals. We also review the
      emerging evidence pertaining to antimicrobial phylloplane proteins and mechanisms
      by which proteins can be released to the phylloplane, including biosynthesis
      (e.g. phylloplanins) by specific trichomes and delivery in guttation fluid from
      hydathodes. Future research should lead to exciting advances in our understanding
      of the phylloplane and to useful biotechnological interventions.

PMID- 17208511
TI  - Gray-scale and geometric registration of full-field digital and film-screen
      mammograms.
AB  - During the transition from traditional film-screen (FS) mammography to full-field
      digital (FFD) mammography, images from both modalities are used in hospitals and
      in mammography screening centers, as comparison of mammograms from subsequent
      examinations of a client is an important part of the diagnostic procedure. A
      parametric method is presented to register a FS mammogram and a FFD mammogram of
      the same woman with respect to geometry and gray-scales. The main motivation for
      the study is to lessen irrelevant differences between mammograms due to
      acquisition. First, a technique like this might increase the radiologist's
      ability to detect relevant differences like abnormal growth in breast tissue that
      signal breast cancer. Second, applications may be found in subtraction radiology
      or in computer-aided detection of abnormalities in temporal mammograms. The
      proposed method is based on a parametric model of the most important aspects of
      acquisition, which relates the pixel values of two images. This encompasses (1)
      breast positioning; (2) breast compression; (3) exposure time; (4) incident
      radiation intensity; and (5a) film properties and digitization for FS mammograms,
      or (5b) detector response for FFD mammograms. The method does not require a
      priori knowledge about specific settings of acquisition; the parameters are
      estimated from the two mammograms themselves.

PMID- 17208512
TI  - Neutrophil extracellular traps: casting the NET over pathogenesis.
AB  - Neutrophil extracellular traps (NETs) are considered to be part of the human
      innate immunity because they trap and kill pathogens. NETs are formed by
      activated neutrophils and consist of a DNA backbone with embedded antimicrobial
      peptides and enzymes. They are involved in host defense during pneumococcal
      pneumonia, streptococcal necrotizing fasciitis, appendicitis and insemination.
      Recently, bacterial virulence factors that counteract NETs have been identified.
      These include the degradation of the NET-backbone by DNases enabling the
      liberation of bacteria from NETs, as well as capsule formation, which reduces
      bacterial trapping. Furthermore, pathogens can resist NET-mediated killing by
      adding positive charge to their cell surface.

PMID- 17208513
TI  - Persistent bacterial infections and primary immune disorders.
AB  - Mycobacteria, Salmonella and Helicobacter species have all evolved mechanisms to
      evade host defenses and cause persistent infection in humans. Host control of
      mycobacteria and Salmonella is largely achieved by the IFN-gamma/IL-12 pathway.
      Immune disorders affecting this pathway are characterized by disseminated
      infections with environmental or nontuberculous mycobacteria. Helicobacter is a
      predominantly extracellular bacterium that uses its remarkable genetic diversity
      (as well as other mechanisms) in order to evade host defenses. The importance of
      humoral immunity in containing Helicobacter infections to the mucosal surface is
      illustrated by the primary immune disorder, X-linked agammaglobulinemia in which
      patients are prone to chronic bacteremia and skin infections by Helicobacter and
      related species such as Flexispira and Campylobacter. Exploration of these
      particular infections in their specific immune defects sheds light on both host
      and bacterial mechanisms that have implications for pathogenesis and therapy.

PMID- 17208514
TI  - c-di-GMP-mediated regulation of virulence and biofilm formation.
AB  - It is now apparent that the signaling molecule 3',5'-cyclic diguanylic acid (c-di
      GMP) is a central regulator of the prokaryote biofilm lifestyle and recent
      evidence also links this molecule to virulence. Environmentally responsive signal
      transduction systems that control expression and/or activity of the enzymes
      (GGDEF and EAL domain containing proteins) that are responsible for synthesis and
      degradation of c-di-GMP have recently been identified. Members of the
      phosphorelay family feature prominently amongst these systems, which include
      several with hybrid polydomain sensors and one that is similar to well
      characterized chemotaxis-controlling pathways. These findings support the
      hypothesis that c-di-GMP levels are tightly controlled in response to a broad
      range, in terms of both diversity and intensity, of extracellular signals.
      Insight into how c-di-GMP affects changes in gene expression and/or protein
      activity has come from the demonstration that proteins containing the PilZ domain
      can bind c-di-GMP and control phenotypes involved in biofilm formation and
      virulence. These recent developments should pave the way for researchers to
      answer the important question of how a vast array of extracellular signals that
      are sensed by multiple sensory transduction pathways which all lead to the
      production or destruction of c-di-GMP are coordinated such that the appropriate
      phenotypic response is produced.

PMID- 17208515
TI  - The role of bacterial pathogens in cancer.
AB  - The association of Helicobacter pylori with gastric cancer is the best-studied
      relationship between a bacterial infection and cancer. Other bacterial pathogens
      in humans and rodents are now being recognized as potentially having a direct
      role in carcinogenesis. Thus, it might be possible to understand the pathogenesis
      and prevention of certain cancers by studying the bacterial infections associated
      with them, and their effects on the host. However, the mechanisms by which
      bacteria contribute to cancer formation are complex, and recent investigations
      show that they involve the interplay between chronic inflammation, direct
      microbial effects on host cell physiology and, ultimately, changes in tissue stem
      cell homeostasis.

PMID- 17208516
TI  - A web-based patient education system and self-help group in Persian language for
      inflammatory bowel disease patients.
AB  - BACKGROUND AND AIMS: To study the use patterns of a Persian web-based patient
      education system for inflammatory bowel disease (IBD) patients in Iran. METHODS:
      A web-based patient education system was developed with Persian content in three
      sections: general, ulcerative colitis (UC), and Crohn's disease (CD). The website
      included a forum for patients to communicate as a self-help group. A customized
      web tracking system recorded web use statistics. Polls at the bottom of each page
      collected the visitors' opinion on the extent of helpfulness and readability of
      page contents. Web use data were analyzed for an 18-month period from October
      2004 to April 2006. RESULTS: Having excluded page visits from search engine
      robots, the website's homepage was visited 4452 times (mean of monthly visits:
      234, range: 102-330). The web pages titled Anatomy of gastrointestinal system,
      Nutrition in IBD, Diagnostic tests, How to cope with IBD, and IBD in women were
      the most favorite in general section. The web page titled IBD treatment was the
      most visited in both CD and UC sections followed by the web pages on cause of
      disease, diagnostic procedures and complications in CD section; and those titled
      symptoms, cause of disease and risk factors in the UC section. Overall, the
      content evaluation polls received 294 hits (from 186 unique visitors) of which,
      196 (67%) were from patients, 30 (10%) from patients' relatives/friends, 21 (7%)
      from doctors, and 47 (16%) from other groups. During the 18-month period, 47
      patients registered in the self-help forum, 24 threads were opened, and 97 posts
      (33 in CD and 64 in UC section) were sent. CONCLUSIONS: Considering the
      increasing trend of Internet use in developing countries like Iran, and the
      consequent increase in the proportion of Internet-using patients, and finally the
      time constraints gastroenterologists face answering patients' questions; similar
      websites seem to be effective ways of patient education in close future.

PMID- 17208517
TI  - The neural representation of odor is modulated by the presence of a trigeminal
      stimulus during odor encoding.
AB  - OBJECTIVES: Odor perception does not simply consist in hierarchical processing
      from transduction to a single "true" cerebral representation. Odor sensation may
      be modulated by available sensory information during encoding. The present study
      set out to examine whether the presence of a pure trigeminal stimulus during odor
      encoding may modulate odor perception at both behavioral and cortical levels.
      METHODS: Participants were tested in a 2-session within-subject design: first, an
      odor encoding session included a delay conditioning procedure in which relatively
      selective olfactory stimulants (phenyl ethyl alcohol or vanillin, Conditioned
      Stimulus+, CS+) were presented either with a pulse of CO(2) (Unconditioned
      Stimulus, US), or alone (Conditioned Stimulus-, CS-); then, in the second
      session, both pure odorants (CS+ and CS-) were presented alone. During this
      second session, olfactory event-related potentials were simultaneously recorded
      and analyzed at different electrode sites including Cz and Pz (sites known to
      have maximal amplitudes for trigeminal and olfactory stimuli, respectively).
      After each trial, subjects were asked to rate odor intensity and hedonics.
      RESULTS: The results showed that CS+ intensity ratings increased in 8 subjects
      and decreased in 6. Cortically, a group effect was observed for P2 amplitude,
      which increased in the "CS+ intensity increase" group vs. the "CS+ intensity
      decrease" group at Cz (p<0.05) but not at Pz (p>0.05). CONCLUSIONS: This result
      suggests that the presence of a pure trigeminal stimulus (CO(2)) during odor
      encoding alters the neural representation of a pure odor. SIGNIFICANCE: The
      neural representation of odors comprises not only the odor itself but also
      contextual information (trigeminal in the present case) presented during
      encoding.

PMID- 17208519
TI  - Tuberculosis subunit vaccine design: the conflict of antigenicity and
      immunogenicity.
AB  - The attempts to find an effective antituberculous subunit vaccine are based on
      the assumption that it must drive a Th1 response. In the absence of effective
      correlates of protection, a vast array of mycobacterial components are being
      evaluated worldwide either on the basis of their ability to be recognized by T
      lymphocytes in in vitro assays during early stage of animal or human infection
      (antigenicity) or their capacity to induce T cell response following immunization
      in animal models (immunogenicity). The putative vaccine candidates selected using
      either of these strategies are then subjected to challenge studies in different
      animal models to evaluate the protective efficacy. Here we review the outcome of
      this current scheme of selection of vaccine candidates using an 'antigenicity' or
      'immunogenicity' criterion on the actual protective efficacy observed in
      experimental animal models. The possible implications for the success of some of
      the leading vaccine candidates in clinical trials will also be discussed.

PMID- 17208520
TI  - Stress and anxiety associated with prenatal diagnosis.
AB  - Prior to any specific prenatal diagnostic procedure, the pregnant woman should be
      counselled about the indications for the procedure and how the diagnosis would
      inform care. In addition, the risks and limitations should be clearly spelt out.
      The availability of non-invasive prenatal diagnostic procedures such as
      sonography appears to have led to a higher rate of acceptance of such procedures,
      especially in younger patients. The expectations of pregnant women and their
      partners concerning prenatal diagnosis focus on reducing uncertainty in regard to
      the normality of the pregnancy. However, any prenatal diagnostic procedure can
      cause emotional stress in the pregnant woman. There are two different types of
      stress in this situation. There may be anxiety about the invasive nature of the
      procedure and the attendant risk of the loss of a wanted pregnancy. There may
      also be anxiety over the outcome of the investigation. Any unexpected finding,
      especially an abnormal one, often has an adverse impact on the pregnant woman and
      her partner. Imaging of the unborn child on sonography, and revealing fetal
      movements and heartbeat, are increasingly a common and key experience in a
      pregnancy. With the advent of this now commonly shared experience, the male
      partner also gives up his roll as a passive onlooker and becomes more actively
      involved in the pregnancy. Couples require multidisciplinary care if an abnormal
      fetus is found.

PMID- 17208518
TI  - Antigen receptor signalling: a distinctive role for the p110delta isoform of
      PI3K.
AB  - The activation of antigen receptors triggers two important signalling pathways
      originating from phosphatidylinositol(4,5)-bisphosphate [PtdIns(4,5)P(2)]. The
      first is phospholipase Cgamma (PLCgamma)-mediated hydrolysis of PtdIns(4,5)P(2),
      resulting in the activation of Ras, protein kinase C and Ca(2+) flux. This
      culminates in profound alterations in gene expression and effector-cell
      responses, including secretory granule exocytosis and cytokine production. By
      contrast, phosphoinositide 3-kinases (PI3Ks) phosphorylate PtdIns(4,5)P(2) to
      yield phosphatidylinositol(3,4,5)-trisphosphate, activating signalling pathways
      that overlap with PLCgamma or are PI3K-specific. Pathways that are PI3K-specific
      include Akt-mediated inactivation of Foxo transcription factors and transcription
      independent regulation of glucose uptake and metabolism. The p110delta isoform of
      PI3K is the main source of PI3K activity following antigen recognition by B
      cells, T cells and mast cells. Here, we review the roles of p110delta in
      regulating antigen-dependent responses in these cell types.

PMID- 17208521
TI  - Glutathione S-transferase from the Icelandic scallop (Chlamys islandica):
      isolation and partial characterization.
AB  - Glutathione S-transferase from the digestive gland of the cold-adapted marine
      bivalve Icelandic scallop was purified to apparent homogeneity by single GSTrap
      chromatography. The enzyme appeared to be a homodimer with subunit M(r) 22,000
      having an optimum catalytic activity at pH 6.5-7. Enzymatic analysis of scallop
      GST using the substrates 1-chloro-2,4-dinitrobenzene (CDNB) and glutathione
      resulted in apparent values for K(m)(GST) and K(m)(CDNB) of 0.3 mM and 0.4 mM,
      respectively. The scallop GST lost activity faster than porcine GST when exposed
      to increased temperatures, but both enzymes needed 10 min incubation at 60
      degrees C for complete inactivation. A partial coding sequence was identified in
      cDNA synthesised from digestive gland mRNA. Comparison to known sequences
      indicates that the gene product is a glutathione S-transferase, and the predicted
      Icelandic scallop GST protein scores 40% sequence identity and 60% sequence
      similarity to mu-class proteins.

PMID- 17208522
TI  - The intricate structural chemistry of base excision repair machinery:
      implications for DNA damage recognition, removal, and repair.
AB  - Three-dimensional structures of DNA N-glycosylases and N
      glycosylase/apyrimidine/apurine (AP)-lyase enzymes and other critical components
      of base excision repair (BER) machinery including structure-specific nuclease,
      repair polymerase, DNA ligase, and PCNA tethering complexes reveal the overall
      unity of the simple cut and patch process of DNA repair for damaged bases. In
      general, the damage-specific excision is initiated by structurally-variable DNA
      glycosylases targeted to distinct base lesions. This committed excision step is
      followed by a subsequent damage-general processing of the resulting abasic sites
      and 3' termini, the insertion of the correct base by a repair DNA polymerase, and
      finally sealing the nicked backbone by DNA ligase. However, recent structures of
      protein-DNA and protein-protein complexes and other BER machinery are providing a
      more in-depth look into the intricate functional diversity and complexity of
      maintaining genomic integrity despite very high levels of constant DNA base
      damage from endogenous as well as environmental agents. Here we focus on key
      discoveries concerning BER structural biology that speak to better understanding
      the damage recognition, reaction mechanisms, conformational controls, coordinated
      handoffs, and biological activities including links to cancer. As the three
      dimensional crystal and NMR structures for the protein and DNA complexes of all
      major components of the BER system have now been determined, we provide here a
      relatively complete description of the key complexes starting from DNA base
      damage detection and excision to the final ligation process. As our understanding
      of BER structural biology and the molecular basis for cancer improve, we predict
      that there will be multiple links joining BER enzyme mutations and cancer
      predispositions, such as now seen for MYH. Currently, structural results are
      realizing the promise that high-resolution structures provide detailed insights
      into how these BER proteins function to specifically recognize, remove, and
      repair DNA base damage without the release of toxic and mutagenic intermediates.

PMID- 17208523
TI  - Tyrosine83 is essential for the activity of E. coli galactoside transacetylase.
AB  - The gene (lacA) coding for Escherichia coli galactoside transacetylase was cloned
      into the pTrcHisB plasmid, and the corresponding hexahistidine-tagged enzyme was
      over-expressed and purified. The kinetic constants of the tagged protein were
      determined, yielding values in excellent agreement with previous observations
      reported for the natural enzyme. LacA Tyrosine83 was then substituted with a
      Valine: by comparing the K(m) and k(cat) values observed for wild type and mutant
      enzymes using isopropyl-thio-beta-d-galactopyranoside or p-nitrophenyl-beta-d
      galactopyranoside as substrates, Tyrosine83 was identified as an essential
      residue for the catalytic activity of E. coli galactoside transacetylase.

PMID- 17208524
TI  - Aggregation as the basis for complex behaviour of cutinase in different
      denaturants.
AB  - We have previously described the complexity of the folding of the lipolytic
      enzyme cutinase from F. solani pisi in guanidinium chloride. Here we extend the
      refolding analysis by refolding from the pH-denatured state and analyze the
      folding behaviour in the presence of the weaker denaturant urea and the stronger
      denaturant guanidinium thiocyanate. In urea there is excellent consistency
      between equilibrium and kinetic data, and the intermediate accumulating at low
      denaturant concentrations is off-pathway. However, in GdmCl, refolding rates, and
      consequently the stability of the native state, vary significantly depending on
      whether refolding takes place from the pH- or GdmCl-denatured state, possibly due
      to transient formation of aggregates during folding from the GdmCl-denatured
      state. In GdmSCN, stability is reduced by several kcal/mol with significant
      aggregation in the unfolding transition region. The basis for the large variation
      in folding behaviour may be the denaturants' differential ability to support
      formation of exposed hydrophobic regions and consequent changes in aggregative
      properties during refolding.

PMID- 17208525
TI  - Diagnosis and treatment: gallstone ileus.

PMID- 17208526
TI  - New perspectives for the use of contrast-enhanced liver ultrasound in clinical
      practice.
AB  - The introduction of second-generation microbubble ultrasound contrast agents and
      the development of contrast specific ultrasound techniques have improved the
      ability of contrast enhanced ultrasound in detecting and characterising liver
      lesions, offering new perspectives for its exploitation in clinical hepatology.
      Indeed, several studies have demonstrated a high diagnostic accuracy in focal
      lesion characterisation (85-96%) in patients either with or without underlying
      chronic liver disease. This review article describes the basic principles of
      contrast enhanced ultrasound, defines the different vascular features of benign
      and malignant liver lesions, and assesses its clinical impact in different
      clinical scenarios, according to the guidelines of the European Federation of
      Societies for Ultrasound in Medicine and Biology, contrast enhanced ultrasound
      enables the characterisation of focal liver lesions, regardless of the presence
      or absence of underlying chronic liver disease. Contrast enhanced ultrasound is
      also useful in staging and follow-up of cancer patients and in monitoring local
      ablative treatment. Contrast enhanced ultrasound is expected to be considerably
      increased and replace many computed tomography and magnetic resonance imaging
      examinations in near future, according to the European Federation of Societies
      for Ultrasound in Medicine and Biology guidelines. Therefore, it is necessary to
      take measures in order to meet the demand for an increasing number of these
      procedures.

PMID- 17208527
TI  - The exoskeleton of the lobster Homarus americanus as an example of a smart
      anisotropic biological material.
AB  - Many biological materials are composed of fibrils arranged according to well
      ordered three-dimensional patterns. These materials often show a strong
      anisotropy in their properties. An essential characteristic of biological
      structures is their hierarchical organization from the nanometer to the
      millimeter scale. Lobster cuticle is a good example of this and a suitable model
      for studying these properties. In this study the structure of untreated as well
      as chemically and physically treated cuticle from the exoskeleton of the American
      lobster (Homarus americanus) was investigated using scanning electron microscopy.
      Fresh samples have been chemically decalcified and deproteinated and thermally
      treated to evaluate their resistance to degradation. Results showed that their
      structure is more complex than the commonly assumed model for arthropod cuticles.
      Stacked chitin-protein planes create the characteristic twisted plywood pattern
      found in arthropod cuticles. However, due to a well-developed pore canal system
      these planes are not simple arrays of parallel chitin-protein fibers. In lobster
      cuticle, interconnected fibers bend around the continuous lenticellate cavities
      of the pore canals to form a planar honeycomb-like structure. The chemically and
      thermally treated samples showed that the organic matrix retains its shape and
      structure despite the attack of chemical compounds or heat. It was also possible
      to study the distribution of the biominerals after the removal of the organic
      matrix. The observed residual structure gives a good impression of how the
      minerals (mainly calcite) are distributed inside the polymeric network.

PMID- 17208528
TI  - Re: "Cross-sectional reference data for phalangeal quantitative ultrasound from
      early childhood to young-adulthood according to gender, age, skeletal growth, and
      pubertal development" by Baroncelli et al.

PMID- 17208529
TI  - Congenital double anus with total colon duplication: a case report.
AB  - Cases of congenital double anus are very rare. The number of cases of hindgut
      duplication of all kinds is slightly higher, and some series include patients
      with genitourinary and genitalia duplications but with a single anus. However,
      double termination with tubular duplication is rarely heard of. We report on the
      case of a patient with 2 well-formed ani, total colon duplication, and 2 vaginas.

PMID- 17208530
TI  - Acute acalculous cholecystitis as the initial presentation of primary Epstein
      Barr virus infection.
AB  - The case of a 13-year-old girl with primary Epstein-Barr virus (EBV) infection
      and concomitant cholestatic hepatitis, which initially presented as acute
      acalculous cholecystitis (AAC), is described. The diagnosis of AAC was documented
      by clinical and ultrasonographic criteria, whereas acute EBV infection was
      confirmed serologically. AAC may develop during the course of acute EBV
      infection, especially in patients with cholestatic hepatitis.

PMID- 17208531
TI  - Neonatal intrapericardial teratoma: a challenge for the pediatric surgeon.
AB  - Congenital intrapericardial teratoma can present in the fetal and neonatal
      period, but prenatal diagnosis is difficult. Its clinical course, similar to that
      of an anterior mediastinal mass, may be fatal if the tumor is not promptly
      excised. We report the case of a fetus with a large anterior mediastinal mass
      associated with hydramnios, pleural effusion, and ascites. Perinatal surgical
      removal is the only lifesaving therapy; any conservative approach in these
      neonates should be avoided even if critically symptomatic.

PMID- 17208532
TI  - Tracheal diaphragm: a very unusual form of congenital tracheal stenosis.
AB  - A 3.2-kg newborn was intubated for neonatal respiratory distress owing to a
      congenital tracheal stenosis. The preoperative assessment showed a sphincter-like
      stenosis located 1 cm above the carina. The child was cured by resection
      anastomosis through sternotomy under cardiopulmonary bypass. The pathological
      examination showed hypoplastic cartilage islets embedded in a fibroelastic
      conjunctive tissue. The posterior membranous region was preserved with the
      existence of smooth muscle cells. This curious malformation resembled a diaphragm
      at the junction between trachea and carina.

PMID- 17208533
TI  - Is angiogenesis an organizing principle in biology and medicine?

PMID- 17208534
TI  - Robert E. Gross Lecture. Fetomaternal cell trafficking: a story that begins with
      prenatal diagnosis and may end with stem cell therapy.

PMID- 17208535
TI  - Matched analysis of nonoperative management vs immediate appendectomy for
      perforated appendicitis.
AB  - BACKGROUND: The role of nonoperative therapy vs immediate appendectomy in the
      management of children with perforated appendicitis remains undefined. The
      objective of this study was to rigorously compare these management options in
      groups of patients with matched clinical characteristics. METHODS: Multicenter
      case-control study was conducted from 1998 to 2003. We compared patients treated
      nonoperatively vs those undergoing appendectomy to identify differences in 12
      clinical parameters. We then generated a second control group of patients matched
      for these variables and compared the following outcomes in these clinically
      similar groups: complication rate, abscess rate, and length of stay (LOS).
      Analysis was performed according to intention-to-treat principles, using chi2,
      Fisher exact, and Student t tests. RESULTS: The only significant difference
      between patients treated nonoperatively and those treated by appendectomy was the
      duration of pain on presentation (6.8 vs 3.1 days of pain). We created a second
      control group of patients undergoing immediate appendectomy matched on duration
      of pain on presentation to patients treated nonoperatively. These groups
      continued to be clinically comparable for the other 11 parameters. Compared to
      this matched control group, the nonoperative group had fewer complications (19%
      vs 43%, P < .01), fewer abscesses (4% vs 24%, P < .01), and a trend for shorter
      LOS (6.5 +/- 5.7 vs 8.8 +/- 6.7 days, P = .08). CONCLUSIONS: When nonoperative
      management for perforated appendicitis was studied using appropriately matched
      clinical controls, we found that it resulted in a lower complication rate and
      shorter LOS in the subset of patients presenting with a long duration of pain.
      Our data suggest that nonoperative management should be prospectively evaluated
      in children with perforated appendicitis presenting with a history of pain
      exceeding 5 days.

PMID- 17208536
TI  - Use of esophagocrural sutures and minimal esophageal dissection reduces the
      incidence of postoperative transmigration of laparoscopic Nissen fundoplication
      wrap.
AB  - OBJECTIVES: Herniation of the fundoplication wrap through the esophageal hiatus
      is a common reason for surgical failure in children who have undergone
      laparoscopic Nissen fundoplication. Extensive mobilization of the
      gastroesophageal junction in combination with decreased adhesions after
      laparoscopy may contribute to the development of this complication. In an attempt
      to decrease the incidence of wrap migration, we changed our technique to minimal
      mobilization of the intraabdominal esophagus and to placement of esophageal
      crural sutures. In this study, we investigate the impact of these modifications
      on outcome. METHODS: A retrospective analysis was performed on all patients
      undergoing laparoscopic fundoplication by the senior author (GWH) from January
      2000 through December 2004. Those undergoing operation with extensive esophageal
      mobilization and without esophagocrural sutures (January 2000 to March 2002)
      (group I) were compared with those in whom there was minimal esophageal
      dissection with placement of these esophagocrural sutures (April 2002 to December
      2004) (group II). RESULTS: Two hundred forty-nine patients underwent laparoscopic
      Nissen fundoplication during the study period. One hundred thirty patients were
      in group I, and 119 patients were in group II. The rate of transmigration
      decreased from 12% in group I to 5% in group II (P = .072). The relative risk of
      transmigration with extensive esophageal mobilization and without the
      esophagocrural sutures was 2.29. CONCLUSIONS: This retrospective study has shown
      that placement of esophagocrural sutures and minimization of the dissection
      around the esophagus results in a more than 2-fold reduction in the risk of wrap
      transmigration after laparoscopic Nissen fundoplication.

PMID- 17208537
TI  - Pouch outcomes among children with ulcerative colitis treated with calcineurin
      inhibitors before ileal pouch anal anastomosis surgery.
AB  - PURPOSE: The purpose of this article is to describe the outcomes of the pouches
      of 14 children with ulcerative colitis (UC) who were pretreated with calcineurin
      inhibitors before they underwent their ileal pouch anal anastomosis (IPAA)
      surgery. METHODS: An institutional review board-approved retrospective review of
      the charts of consecutive patients with UC treated with calcineurin inhibitors
      before undergoing IPAA surgery at a tertiary pediatric center between 1998 and
      2003 was performed. The primary endpoint was pouch outcome after at least 2 years
      of follow-up (healthy pouch, acute pouchitis, chronic refractory pouchitis, or
      pouch failure); the secondary endpoints were early postoperative complications,
      number of stages, and time between stages. RESULTS: Fourteen of 53 consecutive
      patients who underwent IPAA for UC were treated with calcineurin inhibitors
      before their surgery (26%; 6 with cyclosporine and 8 with tacrolimus). All 14
      patients were concomitantly treated with systemic steroids. Ten patients (71%)
      were also taking 6-mercaptopurine or azathioprine, and 9 (64%) were also taking
      mesalamine. Three patients (21%) had healthy pouches with no clinical evidence of
      pouchitis, 6 (43%) had at least one episode of acute pouchitis (average of 2
      episodes per year), 3 (21%) had chronic relapsing pouchitis, and 2 (14%) were
      later determined to have Crohn's disease. There was no pouch failure. Two
      patients (14%) had an early postoperative complication (intraabdominal abscess,
      anastomotic stricture). Five patients (36%) had a 2-staged procedure, and 8 (64%)
      had a 3-staged procedure. For the 2-staged procedures, the mean time between the
      first and second stages was 3.14 months (range, 3-4 months). For the 3-staged
      procedures, the mean time between the first and second stages was 4.25 months
      (range, 2-6 months) and that between the second and third stages was 4 months
      (range, 2.5-6 months). CONCLUSIONS: In this series, chronic pouchitis was an
      infrequent complication among children who were pretreated with calcineurin
      inhibitors. Calcineurin inhibitor use did not lead to or portend increased early
      postoperative complications or affect the number or duration of surgical stages.
      Further studies are required to determine if preoperative calcineurin inhibitors
      improve pouch outcomes or facilitate the performance of 2-staged procedures.

PMID- 17208538
TI  - Evolution of the technique in the transanal pull-through for Hirschsprung's
      disease: effect on outcome.
AB  - BACKGROUND: The transanal pull-through has become the standard operation for
      Hirschsprung's disease in many pediatric surgical centers. Over the past 8 years,
      we have modified our technique by leaving a short-rather than a long-rectal cuff
      and by doing routine intraabdominal colonic biopsies through an umbilical
      incision before beginning the anal dissection. The aim of this study was to
      determine if these modifications have changed the outcome for children undergoing
      this operation. METHODS: A retrospective cohort study of all patients who
      underwent transanal pull-through by a single surgeon between 1997 and 2005 was
      conducted. RESULTS: There were 23 children who had a long cuff (10-15 cm) and 22
      who had a short cuff (<2 cm). The short cuff group tended to be younger (25 +/-
      23 vs 139 +/- 67 days; P < .05) and smaller (3.5 +/- 0.7 vs 6.0 +/- 2.7 kg; P <
      .05) at the time of surgery. The operating time was shorter (167 vs 186 minutes;
      P = .05) in the short cuff group. Outcomes were improved in the short cuff group,
      as evidenced by decreased hospital stay (1.9 +/- 0.6 vs 2.7 +/- 0.9; P < .05),
      decreased incidence of enterocolitis (9% vs 30%; P = .1), and lower incidence of
      narrowing requiring daily dilatations (5% vs 30%; P < .05). Preliminary colonic
      biopsy was performed on 18 of the 45 patients. This had no significant effect on
      narcotic use (66% vs 70%; P = .8) and did not increase operating time (174 +/- 31
      vs 179 +/- 34 minutes; P = .6). Hospital stay was shorter in the umbilical biopsy
      group (1.9 +/- 0.6 vs 2.6 +/- 0.9 days; P = .006). CONCLUSION: Results of the
      transanal pull-through have improved likely as a result of a combination of
      experience and use of a shorter rectal muscular cuff. The use of a preliminary
      colonic biopsy through an umbilical incision has not increased postoperative
      pain, prolonged operative time, or lengthened hospital stay.

PMID- 17208539
TI  - Are the long-term results of the transanal pull-through equal to those of the
      transabdominal pull-through? A comparison of the 2 approaches for Hirschsprung
      disease.
AB  - PURPOSE: The transanal endorectal pull-through (TERPT) is becoming the most
      popular procedure in the treatment of Hirschsprung disease (HD), but
      overstretching of the anal sphincters remains a critical issue that may impact
      the continence. This study examined the long-term outcome of TERPT versus
      conventional transabdominal (ABD) pull-through for HD. METHODS: Records of 41
      patients more than 3 years old who underwent a pull-through for HD (TERPT, n =
      20; ABD, n = 21) were reviewed, and their families were thoroughly interviewed
      and scored via a 15-item post-pull-through long-term outcome questionnaire.
      Patients were operated on between the years 1995 and 2003. During this time, our
      group transitioned from the ABD to the TERPT technique. Total scoring ranged from
      0 to 40: 0 to 10, excellent; 11 to 20 good; 21 to 30 fair; 31 to 40 poor. A 2
      tailed Student t test, analysis of covariance, as well as logistic and linear
      regression were used to analyze the collected data with confidence interval
      higher than 95%. RESULTS: Overall scores were similar. However, continence score
      was significantly better in the ABD group, and the stool pattern score was better
      in the TERPT group. A significant difference in age at interview between the 2
      groups was noted; we therefore reanalyzed the data controlling for age, and this
      showed that age did not significantly affect the long-term scoring outcome
      between groups. CONCLUSION: Our long-term study showed significantly better (2
      fold) results regarding the continence score for the abdominal approach compared
      with the transanal pull-through. The stool pattern and enterocolitis scores were
      somewhat better for the TERPT group. These findings raise an important issue
      about the current surgical management of HD; however, more cases will need to be
      studied before a definitive conclusion can be drawn.

PMID- 17208540
TI  - Intravascular administration of tumor tropic neural progenitor cells permits
      targeted delivery of interferon-beta and restricts tumor growth in a murine model
      of disseminated neuroblastoma.
AB  - BACKGROUND: Interferon-beta (IFN-beta) has potent antitumor activity; however,
      systemic toxicity has limited its clinical use. We investigated the potential of
      targeted delivery using tumor-tropic neural progenitor cells (NPCs) transduced to
      express human IFN-beta (hIFN-beta). METHODS: Disseminated neuroblastoma was
      established in SCID mice by tail vein injection of tumor cells. Fourteen days
      after tumor cell inoculation, systemic disease was confirmed with bioluminescence
      imaging (BLI). Mice were then treated by intravenous injection of human F3.C1
      NPCs that had been transduced with a replication deficient adenovirus to
      overexpress hIFN-beta (F3-IFN-beta). Two injections were given: the first at 14
      days and the second at 28 days following tumor cell injection. Control mice
      received NPCs transduced with empty vector adenovirus at the same time points.
      Progression of disease was monitored using BLI. At sacrifice, organ weights and
      histology further evaluated tumor burden. RESULTS: After initiation of therapy,
      BLI demonstrated a significant decrease in the rate of disease progression in
      mice receiving F3-IFN-beta. At necropsy, control mice had bulky tumor replacing
      the liver and kidneys, as well as extensive retroperitoneal and mediastinal
      adenopathy. Impressively, these sites within mice receiving F3-IFN-beta therapy
      appeared grossly normal with the exception of small nodules within the kidneys of
      some of the F3-IFN-beta-treated mice. The accumulation of F3.C1 cells within
      sites of tumor growth was confirmed by fluorescence imaging. Importantly,
      systemic levels of hIFN-beta in the treated mice remained below detectable
      levels. CONCLUSIONS: These data indicate that in this model of disseminated
      neuroblastoma, the tumor-tropic property of F3.C1 NPCs was exploited to target
      delivery of IFN-beta to disseminated tissue foci, resulting in significant tumor
      growth delay. The described novel approach for effective IFN-beta therapy may
      circumvent limitations associated with the systemic toxicity of IFN-beta.

PMID- 17208541
TI  - Induction of cytolytic T lymphocytes against pediatric solid tumors in vitro
      using autologous dendritic cells pulsed with necrotic primary tumor.
AB  - PURPOSE: Effective and generally applicable methods for generating cancer
      vaccines in children have not been defined. Dendritic cells (DCs) are the most
      potent professional antigen-presenting cells capable of activating primary
      cytolytic T cells. We tested the ability of DCs generated from pediatric
      patients' peripheral blood monocytes and pulsed with a necrotic tumor to activate
      autologous tumor-specific cytolytic T cells. METHODS: Tumor and peripheral blood
      cells were obtained from pediatric patients undergoing biopsy or resection for
      advanced solid tumors according to an institutional research board-approved
      protocol and after acquiring informed consent from them. To generate DCs, we
      treated peripheral blood monocytes with granulocyte-macrophage colony stimulating
      factor and interleukin (IL)-4. Maturation was induced with a cytokine cocktail
      (CC) containing tumor necrosis factor-alpha, IL-6, IL-1beta, and prostaglandin
      E2. The DC phenotype was assayed using flow cytometry. Tumor necrosis was induced
      by exposure to UV-B irradiation (1000 mJ). Dendritic cells pulsed with a UV-B
      treated primary tumor and matured with CC were used to stimulate autologous
      peripheral blood lymphocytes weekly. Tumor-specific cytolytic activity was
      assayed using 4-hour 51Cr release. RESULTS: Peripheral blood monocytes isolated
      from pediatric patients differentiated into immature DCs (CD14-, MHCII+ [major
      histocompatibility complex], CD80(low), CD86(low)) in the presence of granulocyte
      macrophage colony stimulating factor and IL-4. Cytokine cocktail induced
      maturation of DCs, as characterized by increased expressions of MHCII, CD83,
      CD80, and CD86. Patients' peripheral blood lymphocytes stimulated in vitro with
      DCs loaded with a necrotic primary tumor and matured with CC specifically lysed
      autologous neuroblastoma in 7 of 9 patients. CONCLUSION: Dendritic cells
      generated from the peripheral blood of children with advanced solid tumors and
      pulsed with a necrotic primary tumor undergo maturation and effectively stimulate
      autologous tumor-specific cytolytic T cells in vitro. We describe a simple method
      for generating a vaccine capable of activating cytotoxic T cells against
      pediatric solid tumors that does not require the genetic identification of tumor
      associated antigens.

PMID- 17208542
TI  - Hepatic hemangiomas: subtype classification and development of a clinical
      practice algorithm and registry.
AB  - PURPOSE: Hepatic hemangiomas, though histologically benign, may be associated
      with significant morbidity and mortality in afflicted infants. The literature
      presents much confusion regarding the natural history and treatment options for
      hepatic hemangiomas. Clinical manifestations range from asymptomatic self
      limiting lesions to congestive heart failure associated with high-volume vascular
      shunting to fulminant hepatic failure with hypothyroidism, abdominal compartment
      syndrome, and death. There has been little rationale to choose among observation,
      corticosteroid, other pharmacologic agents, arterial embolization, hepatic artery
      ligation, resection, or liver transplantation for any given patient. METHODS: We
      analyzed several recent retrospective radiologic analyses and pathologic studies
      to determine whether hepatic hemangiomas could be categorized, allowing
      prediction of their natural history and rational choice of therapies based upon
      their clinical presentation and radiographic appearance. RESULTS: We propose that
      hepatic hemangiomas do not represent a single entity but, rather, 3 principle
      categories of lesions: focal, multifocal, and diffuse. Because these 2 categories
      represent different anatomical and physiologic variants, so, too, may they
      respond differently to previously anecdotally applied treatment regimens. With
      input from international multidisciplinary authorities on hemangiomas, we
      developed and proposed a clinical practice algorithm for the evaluation and
      management of hepatic hemangiomas. Toward that end, we propose a plan to
      institute a web-based international hepatic hemangioma registry. Participants in
      the registry could obtain no-cost centralized review of imaging studies (and
      histology if available) and guidance regarding the management algorithm from an
      established multidisciplinary team. In exchange, the registry will facilitate the
      acquisition of systematic clinical and imaging information. CONCLUSION:
      Longitudinal observation of response to more directed treatment protocols may
      contribute greatly to the understanding of these potentially fatal tumors.

PMID- 17208543
TI  - Patent ductus arteriosus ligation in premature infants: who really benefits, and
      at what cost?
AB  - PURPOSE: Patent ductus arteriosus (PDA) ligation in premature infants has been
      shown to have low surgical morbidity and mortality. Ligation goals include prompt
      improvement in cardiorespiratory failure, with rapid wean from mechanical
      ventilation; less risk of prolonged mechanical ventilation and subsequent chronic
      lung disease (CLD); and survival to discharge. This study was designed to examine
      true morbidity after ligation and elucidate which preoperative factors might
      predict favorable outcomes. METHODS: Institutional review board-approved
      retrospective review of 197 infants less than 38 weeks of gestational age (GA),
      undergoing PDA ligation via thoracotomy between January 1, 1992, and January 1,
      2004. Chronic lung disease defined as need for supplemental oxygen at 36 weeks
      corrected GA. Student t and chi2 tests were used. RESULTS: Mean GA was 27 weeks
      (range, 23-35 weeks), birth weight was 957 g (range, 440-3170 g); infants
      underwent ligation at 16 days of life (range, 1-132 days). Duration of surgery
      was 50.5 minutes (range, 13-150 minutes). Mean postoperative times were 27 days
      to extubation, 60 days to wean from supplemental oxygen, and 84 days to
      discharge. Early extubation (within 10 days of ligation) occurred in only 54
      patients (30%). Only 44 (22%) survived to discharge without CLD. Forty patients
      (20%) died, with respiratory failure the most common cause (70%). In general,
      early extubation, survival without CLD and survival to discharge were associated
      with greater GA and birth weight, higher Apgar scores, greater age and weight at
      surgery, no preoperative intraventricular hemorrhage, lack of ventilator
      dependence, and lower ventilator settings (P < .05). Preoperative amount and
      duration of indomethacin use, chest x-ray findings, and echocardiographic
      assessment of ductus size did not predict favorable outcomes (all P > .05).
      CONCLUSIONS: Most premature infants currently undergoing PDA ligation at our
      institution do not experience the anticipated rapid improvements in
      cardiorespiratory status and go on to develop CLD. Few preoperative variables
      (including radiographic and echocardiographic assessments) definitively predict
      outcomes.

PMID- 17208544
TI  - Vertical expandable prosthetic titanium rib for thoracic insufficiency syndrome:
      a new method to treat an old problem.
AB  - PURPOSE: The vertical expandable prosthetic titanium rib (VEPTR) thoracoplasty is
      a new technique devised for the treatment children with thoracic insufficiency
      syndrome. This study describes our initial experience with this device. METHODS:
      This is a retrospective chart review of all children undergoing VEPTR placement
      between October 2001 and December 2005. RESULTS: Twenty-two patients had 36 VEPTR
      devices placed. Two patients had Jeune syndrome, 19 had scoliosis, and 1 had a
      chest wall resection for tumor. Most had associated carbon dioxide retention,
      pulmonary restrictive disease, or respiratory failure. Eleven patients had
      multiple fused ribs requiring opening thoracostomy. All but the most recent
      patients have undergone sequential VEPTR expansion. All children had
      intraoperative spinal cord monitoring (somatosensory evoked potential). Four
      experienced intraoperative somatosensory evoked potential changes that resolved
      with decreased VEPTR expansion. Seven VEPTR devices required revision for erosion
      through the bone or dislodgment and 3 were removed. Five were outgrown and
      removed or replaced. One eroded soft tissue causing superficial infection that
      resolved with operative revision. Postoperative ventilation/perfusion scans
      improved most in younger children. Two of three children with carbon dioxide
      retention pre-VEPTR had carbon dioxide reduction post-VEPTR. CONCLUSIONS:
      Vertical expandable prosthetic titanium rib (VEPTR) is a new and safe method to
      treat children with thoracic insufficiency syndrome. The VEPTR may decrease
      carbon dioxide retention in some patients and may be most beneficial in younger
      children.

PMID- 17208545
TI  - Magnetic Mini-Mover Procedure for pectus excavatum: I. Development, design, and
      simulations for feasibility and safety.
AB  - BACKGROUND/PURPOSE: Correction of pectus excavatum (PE) results in measurable
      improvement in lung capacity and cardiac performance as well as improved
      appearance and self-image. The Nuss and modified Ravitch approaches attempt to
      correct the chest wall deformity by forcing the sternum forward in 1 step and
      holding it in place using a metal strut. The initial operation requires extensive
      manipulation under general anesthesia and results in postoperative pain,
      requiring hospitalization and regional anesthesia. Pain and disability may last
      for weeks. Both procedures are expensive. A better principle would be a gradual
      bit-by-bit repair via small increments of pressure applied over many months. We
      developed the Magnetic Mini-Mover Procedure and applied this strategy to correct
      PE. METHODS: The Magnetic Mini-Mover Procedure uses magnetic force to pull the
      sternum forward. An internal magnet implanted on the sternum and an external
      magnet in a nonobtrusive custom-fitted anterior chest wall orthosis produce an
      adjustable outward force on the sternum. Outward force is maintained until the
      abnormal costal cartilages are remodeled and the pectus deformity is corrected.
      RESULTS: We implanted a magnet in human skeletons and measured the force applied
      to the sternum when the distance between the internal and external magnets was
      varied in increments. With the 2 magnets 1 cm apart, the outward force was
      adequate to move the sternum at least 1 cm. We also mapped the magnetic field in
      the two-magnet configuration and found that maximum field strengths at the
      surface of the heart and at the outer surface of the orthosis were at safe
      levels. CONCLUSIONS: The Magnetic Mini-Mover Procedure allows correction of PE by
      applying magnetic force over a period of months. Crucial questions raised during
      our design, redesign, and simulation testing have been satisfactorily answered,
      and we have received a Food and Drug Administration Investigation Device
      Exemption (G050196/A002) to proceed with a phase I to II clinical trial.

PMID- 17208546
TI  - Infectious complications after the Nuss repair in a series of 863 patients.
AB  - PURPOSE: A nemesis of surgical implants is infection. We evaluated the various
      infectious complications after Nuss repair of pectus excavatum in 863 patients
      over 18 years. METHODS: After institutional review board approval, a
      retrospective review of a prospectively gathered database of patients was
      performed who underwent minimally invasive repair of pectus excavatum and
      developed an infection. All patients received intravenous antibiotics before
      surgery continuing until discharge. Patients with a persistent fever after
      operation were discharged with oral antibiotics. RESULTS: From January 1987 to
      September 2005, 863 patients underwent a minimally invasive pectus excavatum
      repair and 13 (1.5%) developed postoperative infections. These included 6 bar
      infections, 4 cases of cellulitis, and 3 stitch abscesses. Cellulitis was defined
      as erythema and warmth which responded to a single course of antibiotics. Bar
      infections were defined as an abscess in contact with the bar. Surgical drainage
      and long-term antibiotics resolved 3 of these abscesses, whereas 3 patients
      required early bar removal (1 after 3 months and 2 after 18 months). Cultures
      identified a single organism in each case and Staphylococcus aureus was the most
      common organism (83%) identified, and all being methicillin sensitive. All
      infections occurred on the side of the stabilizer if a stabilizer had been
      placed. CONCLUSIONS: Infectious complications after Nuss repair are uncommon and
      occurred in 1.5% of our patients. Published rates of postoperative infection
      range from 1.0% to 6.8%. Superficial infections responded to antibiotics alone.
      Bar infection occurred in only 0.7% and required surgical drainage and long-term
      antibiotics. Only 3 of these (50% of bar infections and 0.34% overall) required
      early bar removal at 3 and 18 months because of recurring infections. Early bar
      removal should be a rare morbidity with the Nuss repair.

PMID- 17208547
TI  - When it is not an infection: metal allergy after the Nuss procedure for repair of
      pectus excavatum.
AB  - PURPOSE: Increasing use of implantable bars for minimally invasive pectus
      excavatum repair has introduced metal allergy (nickel and chromium) to pediatric
      surgeons. Metal allergy is a well-recognized entity in neurologic, orthopedic,
      and craniofacial surgery. This study was performed to evaluate metal allergy and
      its effects on treatment with the Nuss procedure in 862 patients. METHODS: After
      institutional review board approval, we undertook a retrospective review of a
      prospectively gathered database of patients undergoing the Nuss procedure. Metal
      allergy was diagnosed either with the use of dermal patch or clinically, based on
      rash, fever, elevated erythrocyte sedimentation rate, cultures, and pathology
      specimens. Data collection included demographics, an allergy to jewelry, and
      history of atopy. Clinical outcomes including need for reoperation, removal of
      stainless steel bar, and replacement with titanium bar were evaluated. RESULTS:
      Over an 18-year period (1987-2005), 862 patients underwent the Nuss procedure.
      Nineteen (2.2%) were diagnosed with metal allergy, with an average age of 14.7
      years (9-23 years). Eighteen (95%) were males. A history of atopy was present in
      9 (56%) patients. Ten (63%) patients presented with rash and erythema, 1 (6%)
      with granuloma, 5 (32%) with pleural effusion, and 3 (15%) were diagnosed on
      preoperative screening. Stainless steel bars were removed because of allergic
      skin breakdown in 3 patients, with 2 patients requiring replacement titanium
      bars. In all 3 of these patients, symptoms resolved after removal of stainless
      steel bars. Titanium bars were placed in the 3 patients who were diagnosed
      preoperatively with metal allergy, without event. CONCLUSIONS: Allergy symptoms
      often are misdiagnosed as infection, but require different treatment. If a
      history of metal allergy or atopy is suggested preoperatively, the patient should
      be tested for metal allergy, and if positive, a titanium bar used. Because the
      consequences of metal allergy may include the need to replace the bar, pediatric
      surgeons should be aware of this occurrence.

PMID- 17208548
TI  - Ex utero intrapartum treatment with extracorporeal membrane oxygenation for
      severe congenital diaphragmatic hernia.
AB  - PURPOSE: The purpose of this study was to determine whether ex utero intrapartum
      treatment with extracorporeal membrane oxygenation (EXIT to ECMO) is a reasonable
      approach for managing patients antenatally diagnosed with severe congenital
      diaphragmatic hernia (CDH). METHODS: A 6-year retrospective review was performed
      on fetuses with severe CDH (liver herniation and a lung/head ratio <1.4,
      percentage of predicted lung volume <15, and/or congenital heart disease).
      Fourteen of the patients underwent EXIT with a trial of ventilation. Fetuses with
      poor preductal oxygen saturations despite mechanical ventilation received ECMO
      before their delivery. Maternal-fetal outcomes were analyzed. RESULTS: There were
      no maternal-reported complications. Three babies passed the ventilation trial and
      survived, but 2 of them required ECMO within 48 hours. The remaining 11 fetuses
      received ECMO before their delivery. Overall survival after EXIT-to-ECMO was 64%.
      At 1-year follow-up, all survivors had weaned off supplemental oxygen, but 57%
      required diuretics and/or bronchodilators. CONCLUSION: This is the largest
      reported experience using EXIT to ECMO in the management of severe CDH. The EXIT
      to-ECMO procedure is associated with favorable survival rates and acceptable
      pulmonary morbidity in fetuses expected to have a poor prognosis under
      conventional management.

PMID- 17208549
TI  - Fetal lung-head ratio is not related to outcome for antenatal diagnosed
      congenital diaphragmatic hernia.
AB  - We asked if fetal lung-to-head ratio (LHR) of 1.0 or lower or liver herniation
      had a statistical effect on survival or need for extracorporeal membrane
      oxygenation (ECMO), compared with LHR above 1.0 in patients with congenital
      diaphragmatic hernia (CDH). METHODS: Antenatal records of all patients diagnosed
      with CDH from January of 2002 to June of 2005 were examined. Inclusion criteria
      were isolated left-sided CDH and absence of significant cardiac or other
      anomalies/syndromes, treated solely at this institution. Lung-to-head ratio
      values were compared based on the value currently proposed for fetal
      intervention: LHR of 1.0 or lower vs LHR above 1.0. Outcome was assessed as
      survival (discharge to home) or need for ECMO. RESULTS: Twenty-eight patients met
      inclusion criteria. Overall survival was 86% (24/28). Postnatal survival in
      fetuses with LHR of 1.0 or lower (8/11) was not statistically different from LHR
      above 1.0 (16/17) (73% vs 94%, P = .114). The need for ECMO in the group with LHR
      of 1.0 or lower (3/11) was not significantly different from those with LHR above
      1.0 (1/17) (27% vs 6%, P = .114). Herniation of the fetal liver into the chest
      did not affect survival or need for ECMO (P = .228). CONCLUSION: Neither LHR of
      1.0 or lower nor liver herniation identified a risk factor significant enough to
      warrant fetal intervention. Multicenter studies may be more appropriate to
      investigate this clinical problem.

PMID- 17208550
TI  - Predicting inadequate long-term lung development in children with congenital
      diaphragmatic hernia: an analysis of longitudinal changes in ventilation and
      perfusion.
AB  - PURPOSE: Infants born with congenital diaphragmatic hernia (CDH) demonstrate a
      wide variability in postnatal catch-up lung growth. The goals of this study were
      to assess the pulmonary development of children born with CDH using sequential
      ventilation-perfusion (V/Q) scintigraphy and to identify the perinatal factors
      that correspond to a progressive V/Q mismatch. METHODS: The records of 137
      patients seen between 1990 and 2005 in a multidisciplinary CDH clinic were
      reviewed. Changes in the ipsilateral V/Q quotient were compared in 46 patients
      who had 2 or more studies with the following variables: sex, patch repair,
      laterality, gestational age, and use of extracorporeal membrane oxygenation. An
      abnormal V/Q quotient was defined as greater than 1.2 (reference range, 0.8-1.2).
      RESULTS: Abnormal V/Q scans were identified in 28 (61%) of the 46 patients at the
      time of the last V/Q study. Patients who underwent a patch repair had nearly 7
      times the risk (P < .001) of developing an ipsilateral V/Q mismatch. The use of
      extracorporeal membrane oxygenation had a variable effect on the probability of
      an abnormal V/Q study finding. No other variable was significant. CONCLUSIONS:
      Many children with CDH develop significant and progressive V/Q mismatches.
      Although some perinatal variables appear to be predictive of this phenomenon,
      they may simply be surrogates for a greater degree of pulmonary hypoplasia
      present at birth. This subpopulation of CDH survivors is an identifiable group
      clearly at risk and thus requires long-term follow-up.

PMID- 17208551
TI  - Fetal intervention for mass lesions and hydrops improves outcome: a 15-year
      experience.
AB  - PURPOSE: The natural history of certain prenatally diagnosed masses is well
      known. Large thoracic mass lesions can evolve one of 2 ways, either to regress
      and cause minimal morbidity, or to progress and enlarge, often resulting in
      hydropic changes in the fetus. This nonimmune hydrops carries a dismal prognosis,
      with nearly all fetuses expiring before or shortly after birth. However, hydrops
      associated with fetal mass lesions can be halted and even reversed with fetal
      intervention and treatment of the underlying defect. We examined our patients
      with fetal mass lesions to evaluate survival after intervention. METHODS:
      Institutional approval was obtained by the Committee on Human Research. A
      retrospective review was performed of 294 fetuses evaluated over 15 years with
      large mass lesions. All patients were evaluated for evidence of fetal hydrops
      using ultrasound criteria. Patients were divided according to type of
      intervention. Primary outcome measure was 30-day survival after birth. RESULTS:
      (1) Patients without fetal hydrops did not undergo fetal intervention and
      survived to 30 days after birth (167/172, 97%). (2) Patients with fetal mass
      lesions that developed hydrops fared poorly with no intervention (1/33 survival,
      3%), whereas fetuses undergoing prenatal intervention fared much better (15/30
      open, 50%; 3/10 percutaneous, 30%). (3) Four patients with hydropic congenital
      cystic adenomatoid malformation (n = 3) or pulmonary sequestration (n = 1)
      received steroids in preparation for surgery but underwent no intervention, and
      the patients survived the neonatal period. CONCLUSION: Fetuses with prenatal
      diagnoses of masses not associated with hydrops have excellent prognosis with
      survival higher than 95%. Nonimmune hydrops associated with prenatal diagnosis of
      a fetal mass is a devastating complication with less than 5% survival. Open
      resection of a mass causing hydrops resulted in 50% survival, with reversal of
      hydrops in a group with near-uniform fatality. Further investigation is warranted
      regarding the use of minimally invasive prenatal therapies including steroid
      administration for hydropic fetuses.

PMID- 17208552
TI  - Increased heritability of certain types of anorectal malformations.
AB  - PURPOSE: Various lines of evidence point to genetic causes for the diverse
      spectrum of anorectal malformations (ARMs); we therefore studied patterns of
      heritability in a large case series. METHODS: We searched our ARM database for
      all patients having family members with congenital anomalies. This group was
      analyzed to determine the type of ARM and the specific anomalies in affected
      family members. RESULTS: Thirty-nine of 1606 patients (2.4%) had a family member
      with a congenital anomaly. The associated non-ARM anomalies included sacral
      masses and gynecologic, hematologic, esophageal, duodenal, renal, and spinal
      anomalies. Of these, 24 patients (1.4%) had 1 or more family members with an ARM.
      Among females with a positive family history, 73% of patients had either a
      vestibular or perineal fistula, compared with only 36% in patients without a
      family history (P = .0004). Among males, 35% had perineal fistulas compared with
      only 10% of those without affected family members (P = .0051). CONCLUSIONS: A
      positive family history in 1.4% is supportive of a strong genetic component to
      ARM. The risk of having an affected family member is significantly increased in
      the presence of a vestibular or perineal fistula. These new data allow for more
      informed counseling of families with an ARM and support the need for further
      genetic studies.

PMID- 17208553
TI  - Ethics and the pediatric surgeon.
AB  - PURPOSE: Care of infants and children with life-impairing or life-threatening
      congenital and acquired disorders often raises ethical concerns for pediatric
      surgeons. The purpose of this survey was to determine the level of interest in
      clinical ethics and how respondents would manage ethical dilemmas within several
      clinical case scenarios. METHODS: A 12-item validated questionnaire developed by
      the Ethics and Advocacy Committee was provided for the American Pediatric
      Surgical Association (APSA; www.eapsa.org) members on the organizational website.
      General categories of questions included informed consent, patient privacy, and
      what constitutes research. RESULTS: The survey was completed by 235 of the 825
      APSA members; a response rate of 28.4%. The majority (62%) were in academic
      practice, 22% had additional education or an advanced degree in ethics, and 11%
      were members of a hospital ethics committee. There was a clear majority response
      for seven questions. Topics generating the most controversy included the impact
      of consent by minors, decision making in the neurologically devastated child,
      what constitutes research in pediatric surgery, the use of interpreters for
      consent, and patient privacy. Respondents chose a well-referenced manuscript as
      the preferred modality for ethics education of the APSA members. CONCLUSION:
      Pediatric surgeons have a general interest in clinical ethics as it relates to
      the care of their patients. An important mission of the Ethics and Advocacy
      Committee can be to provide education that gives guidance and knowledge to the
      members of APSA on timely topics in surgical ethics.

PMID- 17208554
TI  - Short-term results in 53 US obese pediatric patients treated with laparoscopic
      adjustable gastric banding.
AB  - BACKGROUND: Obesity in the adolescent population has reached epidemic
      proportions. Although diet and behavior modification can help a minority of
      teenagers, most of these patients go on to become obese adults. Recently,
      surgical intervention for morbid obesity has gained increasing support. To date,
      this has only included gastric bypass procedures. However, this procedure carries
      at least a 1% mortality rate even in the hands of the most experienced surgeons.
      Therefore, our center has been using laparoscopic adjustable gastric banding
      (LAGB) to treat adolescents with morbid obesity. This analysis is a report of our
      short-term results in our first 53 patients. METHODS: All adolescents aged 13 to
      17 years who had undergone LAGB at our institution and had been entered into our
      prospectively collected database since 2001 were reviewed. Data collected
      preoperatively included age, sex, race, and body mass index (BMI).
      Postoperatively recorded data included length of stay, operative morbidity, need
      for reoperation, as well as percentage of excess weight loss (%EWL) and BMI at 3
      month intervals. RESULTS: Fifty-three teenagers aged 13 to 17 years (mean, 15.9
      years) underwent LAGB at our institution since September 2001. Of these, 41 were
      female and 12 were male. The mean preoperative weight was 297 +/- 53 lb and the
      mean initial BMI was 47.6 +/- 6.7 kg/m2. The %EWL was 37.5 +/- 17.0 at 6 months,
      62.7 +/- 27.6 at 1 year, and 48.5 +/- 15.6 at 18 months of follow-up. There were
      no intraoperative complications. Two patients had band slips that required
      laparoscopic repositioning, and 2 patients developed a symptomatic hiatal hernia
      that required laparoscopic repair. All of these procedures were performed as
      outpatient procedures. A fifth patient developed a wound infection requiring
      incision and drainage. Other complications included mild hair loss in 5 patients,
      iron deficiency in 4 patients, nephrolithiasis and cholelithiasis in 1 patient,
      and gastroesophageal reflux in 1 patient. CONCLUSIONS: Laparoscopic adjustable
      gastric banding is not only a safe operation for morbidly obese pediatric
      patients, but also represents an effective treatment strategy with a %EWL of
      approximately 50% at both 1 year and 18 months of follow-up. Because of the
      minimal morbidity and complete absence of mortality of the LAGB, it is the
      optimal surgical option for pediatric patients with morbid obesity.

PMID- 17208555
TI  - Isolated liver and multivisceral transplantation for total parenteral nutrition
      related end-stage liver disease.
AB  - PURPOSE: Total parenteral nutrition (TPN) has prolonged survival in children with
      intestinal failure; however, end-stage liver disease owing to TPN-induced
      cholestasis (ESLD-TPN) may preclude its use. ESLD-TPN is an indication for
      isolated liver transplantation (ILT) or multivisceral transplantation (MVT).
      Isolated liver transplantation for ESLD-TPN should only be considered in patients
      who have the potential for enteral autonomy. METHODS: We retrospectively reviewed
      the records of patients with ESLD-TPN who underwent ILT (n = 7) or MVT (n = 5)
      between 1994 and 2005. The median age at the time of transplantation was 10.0
      months. Intestinal failure followed necrotizing enterocolitis (n = 3),
      gastroschisis (n = 3), gastroschisis with volvulus (n = 3), gastroschisis with
      atresia (n = 1), malrotation (n = 1), and megacystis microcolon intestinal
      hypoperistalsis syndrome (n = 1). RESULTS: Isolated liver transplant patients had
      a median length of small bowel of 70 cm and tolerated a median of 50% of enteral
      calories. The median length of small bowel in patients who underwent MVT was 29
      cm, and none tolerated more than 30% of goal enteral feeds. Reduced-size (n = 5)
      and whole-liver (n = 2) allografts were used for patients undergoing ILT.
      Patients undergoing MVT received liver-small bowel-pancreas (n = 4) or liver
      small bowel-pancreas-colon (n = 1). Overall patient survival was 57% in ILT
      (median follow-up = 25.1 months); 3 survivors are TPN independent, and the fourth
      patient requires TPN 3 days/wk. Patient survival was 40% after MVT (median follow
      up = 13.0 months); 1 MVT patient died of abuse 16.9 months after transplant and
      was TPN independent at the time of death. Both survivors are TPN independent.
      Bilirubin levels are within normal range in all survivors. CONCLUSION: Isolated
      liver transplantation for ESLD-TPN in the setting of intestinal failure is a
      viable option in patients who have the potential for enteral autonomy.
      Multivisceral transplantation is the only alternative in patients without the
      potential for intestinal recovery. Survival can be achieved in patients with ESLD
      TPN, but mortality remains high for both procedures.

PMID- 17208556
TI  - Neuroblastoma-derived secretory protein messenger RNA levels correlate with high
      risk neuroblastoma.
AB  - BACKGROUND/PURPOSE: In advanced-stage neuroblastoma, bulky disease and systemic
      dissemination can be controlled with intense surgical and medical therapies;
      however, recurrence rates are very high in this group indicating that residual
      disease is rarely eradicated. The need to detect residual disease and predict
      prognosis is critical to planning appropriate treatment regimens for these
      patients. Recently, neuroblastoma-derived secretory protein (NDSP) was identified
      and cloned from neuroblastoma. METHODS: Using quantitative real-time PCR, we
      tested NDSP messenger RNA (mRNA) expression in 45 neuroblastoma tumor samples and
      5 bone marrow samples. Correlation between NDSP expression and age at diagnosis,
      International Neuroblastoma Staging System, MYCN amplification, and Children's
      Oncology Group risk stratification was analyzed using Spearman nonparametric
      correlation. RESULTS: Neuroblastoma tissue samples show much higher NDSP mRNA
      levels above control in 43 of 45 samples (96%); moreover, these levels correlate
      with the Children's Oncology Group neuroblastoma risk group assignment. We also
      found that bone marrow samples with known tumor infiltration had much higher NDSP
      mRNA levels than bone marrow from patients without metastasis. CONCLUSION: From
      these data, we conclude that NDSP mRNA levels in neuroblastoma tumor tissue
      correlate with risk group assignment and may serve as a marker for metastasis in
      bone marrow.

PMID- 17208557
TI  - Pancreatic alpha-cell differentiation by mesenchyme-to-epithelial transition:
      implications for cell-based therapies in children.
AB  - PURPOSE: Stem cell-derived tissue may provide a curative treatment for children
      with type 1 diabetes. Using an avian model, we have previously shown that foregut
      mesenchyme is able to differentiate into insulin-positive beta-cell islets (B
      islets). Successful clinical islet transplantation, however, is reliant on graft
      tissue containing both insulin- and glucagon-secreting cells. Therefore, in this
      study, we assessed the ability of foregut mesenchyme to differentiate into
      glucagon-positive alpha-cell islets (A islets). METHODS: Chimeric recombinants (n
      = 14) were constructed using chick pancreatic epithelium combined with quail
      stomach mesenchyme from day 4 avian embryos and then cultured in 3 dimensions for
      7 days. Cryosectioned recombinants were analyzed using immunocytochemistry
      against glucagon, insulin, and the quail-specific nucleolar antigen. The A islets
      and B islets were determined to be of solely epithelial, solely mesenchymal, or
      mixed origin according to the coexpression of the quail-specific nucleolar
      antigen. RESULTS: Forty-eight A islets and 34 B islets were analyzed. Eighty-five
      percent of the A islets were solely derived from the epithelium, but, notably, 5%
      were solely derived from the mesenchyme and 10% were of mixed origin. A-islet
      differentiation from foregut mesenchyme was reduced as compared with B islets (P
      = .03). CONCLUSION: We demonstrate that foregut mesenchyme is able to
      differentiate into both alpha and beta cells, albeit with quantitative
      differences. These findings may have important implications for the derivation of
      islet tissue from mesenchymal stem cells to cure juvenile-onset diabetes.

PMID- 17208558
TI  - Interferon beta-mediated vessel stabilization improves delivery and efficacy of
      systemically administered topotecan in a murine neuroblastoma model.
AB  - BACKGROUND: We have recently demonstrated that continuous delivery of interferon
      beta (IFN-beta) stabilizes solid tumor vasculature and improves tumor perfusion.
      In this study, we have further investigated the functional consequences of this
      effect by assessing delivery and efficacy of conventional chemotherapy against
      neuroblastoma xenografts when used in combination with IFN-beta. METHODS: Mice
      with established retroperitoneal tumors received adeno-associated virus vector
      encoding IFN-beta (AAV IFN-beta) or control vector. One week later, at 1 hour
      before sacrifice, a 1 mg/kg i.v. bolus of topotecan (TPT) was given. Intratumoral
      levels of TPT were measured by high-performance liquid chromatography and then
      standardized to plasma levels to determine tumor TPT penetration. Subsequent
      experiments evaluated the antitumor efficacy of topotecan alone or in combination
      with AAV IFN-beta. RESULTS: As observed in prior experiments, AAV IFN-beta
      resulted in a marked increase in tumor vessel association with stabilizing
      perivascular smooth muscle cells. These more "matured" vessels facilitated
      improved tumor TPT penetration (51.2% +/- 4.2%) compared with controls (30.8% +/-
      4.7%, P = .004). In additional cohorts of mice, this resulted in an improved
      antitumor effect. Mice with established tumors (301.8 +/- 18.1 mm3) were treated
      with TPT (1 mg/kg daily for 5 days for 2 consecutive weeks) either alone or in
      combination with AAV IFN-beta (5 x 10(10) vector particles per mouse). Topotecan
      monotherapy resulted in a reduction in mean tumor volume of 12% (264.2 +/- 65.8
      mm3, P = .66). However, when the same regimen was administered to mice receiving
      continuous IFN-beta therapy, a 61% (118.9 +/- 42.3 mm3, P = .004) reduction in
      mean tumor volume was achieved. CONCLUSION: Interferon beta-mediated vessel
      stabilization resulted in improved intratumoral delivery of systemically
      administered TPT, enhancing its antitumor efficacy. This approach of altering the
      tumor vasculature provides a strategy to help overcome solid tumor resistance to
      traditional cytotoxic agents.

PMID- 17208559
TI  - Age-dependent recruitment of neutrophils by fetal endothelial cells: implications
      in scarless wound healing.
AB  - PURPOSE: Fetal dermal wounds heal with minimal inflammation and absent fibrosis.
      Later in gestation, a transition to adult-like healing with marked inflammation
      and scarring is observed. Interaction with endothelial cells (ECs) is imperative
      for leukocyte transmigration, a critical step in the inflammatory cascade. This
      study was embarked upon to determine if gestational age-dependent differences in
      EC function modulate changes in inflammatory response and correlate with the
      healing phenotype. METHODS: Fetal porcine ECs were harvested at days 65 (mid
      gestation), 85 (late gestation), and 100 (near-term) (term = 115 days). Confluent
      monolayers were activated with IL-1beta at 10 and 100 ng/mL and exposed to adult
      neutrophils under static (n = 4 per group) and continuous flow (n = 6 per group)
      conditions. Neutrophil-endothelial interaction was quantified and compared using
      analysis of variance. RESULTS: Under static conditions, the lower cytokine dose
      elicited maximal neutrophil recruitment in later-gestation ECs, while
      midgestation ECs required higher stimulation. Midgestation ECs recruited
      significantly less neutrophils than later gestation ECs at both cytokine
      concentrations under flow conditions. CONCLUSION: There is a gestational age
      dependent variation in neutrophil recruitment by fetal ECs. With minimal
      stimulation, later-gestation ECs actively recruit neutrophils, whereas
      midgestation ECs do not. These findings correlate with the transition period to
      adult-like healing, supporting the potential role of fetal ECs in scarless
      healing.

PMID- 17208560
TI  - The epidemiology of infant injuries and alarming health disparities.
AB  - PURPOSE: Injury epidemiology is the underappreciated foundation of injury
      prevention and control strategies. Given the substantial disparity of infant
      injury-related mortality between African Americans (AA) and whites in our region,
      we sought to better understand the epidemiology of infant injury-related
      mortality rates. METHODS: Our trauma database was reviewed for all infant
      injuries over a 10-year period. The mortality rates were analyzed based on race,
      mechanism, and health insurance type. RESULTS: From 1995 to 2004, 1270 infants
      were identified. Sixty-nine percent were white, 26% AA, and 5% were other.
      Overall mortality was 4.8%. There were significant disparities in mortality
      comparing AA to whites: overall, 9.6% vs 2.8%*; abuse, 15% vs 4%*; suffocation,
      100% vs 55%* (*P < .05). Although 75% of AA vs 40% of whites were insured by
      Medicaid, when separated by insurance type, the disparity in mortality rates
      between races remained significant. CONCLUSIONS: African-American infants have
      3.5 times increased risk of death from preventable injuries compared to white
      infants. This disparity persists despite controlling for type of health
      insurance, a surrogate for socioeconomic status. Understanding these disparities
      and developing injury-prevention programs targeting high-risk mechanisms of
      injury such as abuse and suffocation among AA is critical toward eventually
      eliminating these preventable deaths.

PMID- 17208561
TI  - Pediatric vascular injuries: patterns of injury, morbidity, and mortality.
AB  - PURPOSE: The purpose of this study was to identify the patterns of injury and
      associated morbidity/mortality related to pediatric vascular trauma. METHODS: A
      retrospective review of children and adolescents treated between 1993 and 2005
      was performed. Patients were identified by International Classification of
      Diseases, Ninth Revision codes within an institutional pediatric trauma registry.
      RESULTS: One hundred seventy-six patients with vascular injury were identified.
      Those with injuries isolated to the digits and unspecified vessels were excluded
      (n = 73). The remaining 103 patients were evaluable and are the basis for
      subsequent comparisons. Seventy-four percent of injuries occurred in male
      patients. The average age of the male patients was 11.3 years and that of the
      female patients was 9.1 years (range, 1-18 years; overall, 10.7 years).
      Penetrating wounds caused 68% of the injuries, followed by blunt trauma (31%) and
      burns (0.97%). Anatomical locations of injury included the head/neck (19.4%),
      torso (13.5%), and extremities (67%). Amputation was required in 11 (10.7%)
      patients. The average hospital length of stay of the patients was 12.1 days
      (range, 1-155 days). The overall mortality was 9.7%. Nonoperative management was
      given to 9.7% of the patients; one death caused by carotid injury occurred.
      Overall, 24 patients underwent arteriography, with 1 patient receiving definitive
      treatment in interventional radiology. Of the 103 patients, 29.1% were managed by
      pediatric surgeons, 38.8% were managed by extremity specialists, 17% were managed
      by vascular surgeons, 5.8% were managed by neurosurgeons, and 9.3% were managed
      by others. CONCLUSIONS: Despite the available multidisciplinary diagnostic and
      treatment modalities at tertiary care pediatric trauma centers, traumatic
      vascular injuries in children and adolescents are associated with significant
      morbidity and mortality in contemporary surgical practice.

PMID- 17208562
TI  - Successful liver transplant for unresectable hepatoblastoma.
AB  - BACKGROUND: Treatment of children with stage III and IV hepatoblastoma has shown
      little improvement with 5-year survival rates of 64% and 25%, respectively (J
      Clin Oncol 2000;18:2665-75). A timely and organized treatment program including
      preoperative chemotherapy combined with living donor liver transplantation and
      postoperative chemotherapy has been used seeking improved long-term survival in
      stage III and IV cases. METHODS: A retrospective review of 8 patients with stage
      III and IV hepatoblastoma unresectable by conventional resection were treated
      with complete hepatectomy and transplantation. Approval was obtained from our
      institutional review board. RESULTS: Since August of 2001, we have treated 6
      patients with stage III hepatoblastoma and 2 patients with initial stage IV
      hepatoblastoma. These patients (age, 23 months-9 years) had all received
      extensive chemotherapy or prior resections. After chemotherapy, none had gross
      tumor documented outside of the liver at time of transplantation. All underwent
      hepatectomy including vena cava resection, in selected cases, with living donor
      orthotopic liver transplantation. All patients had at least 2 cycles of
      postoperative chemotherapy. Of 8 patients, 6 are alive and well with normalized
      alpha-fetoprotein levels. There were 2 late deaths from recurrent disease. Length
      of follow-up ranged from 7 to 53 months. CONCLUSION: Complete hepatectomy with
      living donor liver transplantation provides optimal surgical treatment in
      unresectable stage III and initial stage IV disease confined to the liver at
      resection. This series indicates that children tolerate complete hepatectomy,
      transplantation, and postoperative chemotherapy well. Referral to a transplant
      center during the first 3 cycles of chemotherapy appears to offers the best
      opportunity for long-term survival.

PMID- 17208563
TI  - Multiple ectopic lesions of focal islet adenomatosis identified by positron
      emission tomography scan in an infant with congenital hyperinsulinism.
AB  - Congenital hyperinsulinism (HI) exists in 2 histologic forms, focal and diffuse,
      and rarely has been attributed to lesions in ectopic pancreatic tissue. The
      ability to distinguish focal from diffuse HI and locate focal lesions has been
      difficult, thus limiting the optimal management of HI. We present a case of HI
      resulting from focal pancreatic and ectopic pancreatic lesions. After a near
      total pancreatectomy failed to improve the patient's condition, a positron
      emission tomography (PET) scan performed with 18F-fluoro-L-dihydroxyphenylalanine
      demonstrated a focal lesion remaining in the head of the pancreas as well as 4
      hot spots inferior to the remaining pancreas. Surgical exploration found
      pancreatic rests in the jejunum responsible for the hot spots seen on PET.
      Resection of the remainder of the pancreas as well as the small intestinal
      lesions resulted in correction of the patient's HI. Pathology confirmed the
      presence of focal HI lesions in the pancreatic head and small intestinal
      specimens. This case supports the ability of ectopic pancreatic tissue to
      contribute to the pathology of HI. It highlights the ability of PET to
      successfully identify focal lesions, including ectopic tissue, responsible for
      hyperinsulinemic hypoglycemia.

PMID- 17208564
TI  - Percent predicted lung volumes as measured on fetal magnetic resonance imaging: a
      useful biometric parameter for risk stratification in congenital diaphragmatic
      hernia.
AB  - PURPOSE: This study was aimed at determining whether a new method of analyzing
      lung volumes on fetal magnetic resonance (MR) imaging could be used to predict
      the degree of pulmonary compromise in congenital diaphragmatic hernia (CDH).
      METHODS: Seventeen fetuses with CDH were prospectively evaluated by MR. Lung
      volumes were measured using an established technique and expressed as a
      percentage of the predicted lung volume (PPLV). Predicted lung volume was
      determined by subtracting measured mediastinal volume from total measured
      thoracic volume. The PPLV was correlated with postnatal outcomes. Statistical
      analyses were performed using the Mann-Whitney, Spearman correlation, or Fisher
      exact tests (P < .05). RESULTS: Of the 14 liveborn patients, the PPLV was 20.3+/
      10.4 (gestational age at MR, 22.3 +/- 5.7 weeks). The PPLV was significantly
      associated with extracorporeal membrane oxygenation (ECMO) use, hospital length
      of stay, and survival. All patients with a PPLV of less than 15 required
      prolonged ECMO support and had a 40% survival rate. In contrast, only 11% of
      patients with a PPLV of greater than 15 required ECMO, and survival was 100%.
      CONCLUSION: The PPLV as measured by fetal MR imaging can accurately predict
      disease severity in CDH. A value of less than 15 is associated with a
      significantly higher risk for prolonged support and/or death, despite aggressive
      postnatal management.

PMID- 17208565
TI  - Construction of an autologous tissue-engineered venous conduit from bone marrow
      derived vascular cells: optimization of cell harvest and seeding techniques.
AB  - BACKGROUND: Currently available vascular grafts for pediatric cardiovascular
      operations are limited by their inability to grow. Tissue-engineering techniques
      can be used to create vascular grafts with the potential for repair, remodeling,
      and growth. This study demonstrates the feasibility of constructing an autologous
      tissue-engineered venous conduit from bone marrow-derived vascular cells (BMVCs)
      in the ovine animal model. METHODS: Ovine mononuclear cells were isolated from
      the bone marrow, cultured in endothelial growth medium, and characterized with
      immunocytochemistry. Biodegradable tubular scaffolds were constructed from
      polyglycolic acid mesh coated with a copolymer of poly[epsilon-caprolactone-L
      lactide]. Scaffolds were seeded at various cell concentrations and incubation
      times to optimize seeding conditions for the construction of an autologous venous
      conduit. Using optimized conditions, 6 tissue-engineered vascular grafts were
      implanted as inferior vena cava interposition grafts in juvenile lambs. Grafts
      were assessed for patency at days 1 to 30 postoperatively and explanted for
      histological and immunohistochemical analysis. RESULTS: A mixed cell population
      of BMVCs consisting of smooth muscle cells and endothelial cells was cultured
      from ovine sternal bone marrow. A seeding concentration of 2 x 10(6) cells/cm2
      and 7 days of postseeding incubation were optimal for creating a confluent
      cellular layer on the polyglycolic acid/poly[epsilon-caprolactone-L-lactide])
      scaffold. Grafts were explanted up to 4 weeks postoperatively. All grafts were
      patent without evidence of thrombosis. Histological evaluation of the explanted
      grafts demonstrated neo-endothelialization. Graft wall was composed of neo-tissue
      made up of residual polymer matrix, mesenchymal cells, and extracellular matrix
      without evidence of calcification. CONCLUSIONS: Bone marrow-derived vascular
      cells, containing endothelial and smooth muscle cells, can be isolated and
      cultured from ovine sternal bone marrow and used as a cell source for vascular
      tissue engineering. Our optimized techniques for BMVC harvest and seeding onto
      biodegradable scaffolds can be used for studying autologous tissue-engineered
      vascular grafts in the ovine animal model.

PMID- 17208566
TI  - Prophylactic thyroidectomy in pediatric carriers of multiple endocrine neoplasia
      type 2A or familial medullary thyroid carcinoma: mutation in C620 is associated
      with Hirschsprung's disease.
AB  - PURPOSE: Prophylactic total thyroidectomy is now recommended after having
      confirmed RET mutations in children of parents with multiple endocrine neoplasia
      type 2 or familial medullary thyroid carcinoma. We reviewed our experience to
      determine the incidence of medullary thyroid carcinoma with respect to age at
      surgery, the location of the mutation, and its association with Hirschsprung's
      disease (HD). METHODS: A retrospective review from 1996 to 2005 revealed 20
      children with genetic screening for multiple endocrine neoplasia type 2A or
      familial medullary thyroid carcinoma who underwent a prophylactic total
      thyroidectomy with parathyroid gland preservation. RESULTS: The median age of the
      20 patients (9 boys and 11 girls) included in this study was 8.2 years (range,
      3.7-16.9 years) at the time of their surgery. Final pathology revealed normal
      thyroid tissue (n = 3; median age, 5.9 years), C-cell hyperplasia (n = 13; median
      age, 10 years), or medullary thyroid carcinoma (n = 4; median age, 8 years). Four
      children, all with mutations in C620, had a previous diagnosis of HD. At a median
      follow-up of 3.7 years (range, 1 month to 8.4 years), all patients were well and
      cancer free. CONCLUSIONS: There is no correlation between histologic findings and
      median age at surgery. Hirschsprung's disease was found in 50% of the patients
      with the RET mutation in C620. In children of C620 parents, symptoms of HD should
      be actively sought, and if such are found, rectal biopsies should be performed
      even if mutation results are not yet available. Based on the age of the earliest
      cancer and the safety of total thyroidectomy, children should promptly undergo
      surgery after genetic screening and before their fifth year of life.

PMID- 17208567
TI  - Pediatric trauma: experience of a combat support hospital in Iraq.
AB  - BACKGROUND/PURPOSE: The mission of the combat support hospital (CSH) is to
      evaluate and treat combatants injured during war operations. The 31st CSH in
      Balad and Baghdad, Iraq, during Operation Iraqi Freedom 2 also treated many
      injured civilians, including children. The purpose of this article is to report
      the experience of the 31st CSH treating pediatric trauma patients. METHODS: A
      retrospective review of a comprehensive patient database collected in theater was
      conducted. RESULTS: From January 1 to December 31, 2004, we treated 99 patients
      17 years and younger. The average age of these patients was 10.6 years. Nine died
      of their wounds. The mean injury severity score was 11.6. Forty-one sustained
      gunshot wounds, 13 acquired fragment wounds (55% penetrating), and 22 were
      injured by improvised explosive devices (22%). Seventy-three patients required a
      total of 191 operations: 18 celiotomies, 8 craniotomies, 23 skeletal fixations,
      and 75 wound washout/debridements, among others. Predictors of mortality included
      admission Glasgow Coma Score less than 4 and admission pH less than 7.1.
      CONCLUSIONS: The primary mission of the CSH in theater remains unchanged, but its
      role is evolving. With this study, we can begin to understand the needs of
      wounded children in urban conflict and help guide training and resource
      allocation in the future.

PMID- 17208568
TI  - A silver-impregnated antimicrobial dressing reduces hospital costs for pediatric
      burn patients.
AB  - PURPOSE: Since using a novel silver-impregnated antimicrobial dressing (Aquacel
      Ag, ConvaTec, Princeton, NJ) in our pediatric patients with partial-thickness
      burns, hospital LOS has been significantly reduced. Here we investigated whether
      there was concomitant cost-effectiveness of this approach. METHODS: We
      retrospectively reviewed Burn Registry Data from a large Children's Hospital Burn
      Unit from January 2005 through August 2005 for inpatients with partial-thickness
      burns treated with Aquacel Ag. A comparison group was composed of patients from
      the same period the previous year treated with silver sulfadiazine cream (SSD,
      Par Pharmaceuticals, Woodcliff, NJ) and matched for age and %TBSA burned.
      Patients with inhalation injury or full-thickness burns were excluded. Intent-to
      treat analysis was limited to patients with less than 22% TBSA burn. Direct costs
      and total charges were compared statistically after log transformation due to the
      skewedness of the data. RESULTS: Total charges and direct costs were
      significantly lower for Aquacel Ag-treated patients (n = 38) than for SSD-treated
      patients (n = 39) (P = .004 and P < .001, respectively). In addition, Aquacel Ag
      treated patients had a shorter LOS than SSD-treated patients. DISCUSSION: These
      data strongly support our findings that the application of Aquacel Ag reduces
      hospital LOS which results in a significant cost savings in the care of pediatric
      patients with partial-thickness burns.

PMID- 17208569
TI  - Heparin-binding epidermal growth factor-like growth factor promotes enterocyte
      migration and proliferation in neonatal rats with necrotizing enterocolitis.
AB  - PURPOSE: We have shown that heparin-binding epidermal growth factor-like growth
      factor (HB-EGF) decreases experimental necrotizing enterocolitis (NEC).
      Intestinal epithelial cell (IEC) migration (restitution) and proliferation are
      key elements in recovery from intestinal injury. Here, we investigated whether
      the beneficial effects of HB-EGF are mediated, in part, by its ability to affect
      these processes. METHODS: Necrotizing enterocolitis was induced in newborn rats
      by exposure to stress (hypoxia, hypothermia, hypertonic feedings, and
      lipopolysaccharide), with pups receiving different doses of HB-EGF (0, 25, 50,
      100, 200, 400, 600, and 800 microg/kg). To investigate the effect of HB-EGF on
      enterocyte proliferation and migration, bromodeoxyuridine was administered
      intraperitoneally 18 hours before sacrifice, with intestine subjected to
      bromodeoxy-uridine immunohistochemistry. RESULTS: The incidence and severity of
      experimental NEC decreased, and the survival rate increased, with increasing
      doses of HB-EGF. Results were confirmed using scanning electron microscopy.
      Migration of IEC in breast-fed pups was 7.07 microm/h, decreased significantly to
      2.29 microm/h in stressed pups, and was significantly improved at 5.95 microm/h
      in pups subjected to stress but treated with HB-EGF (P < .05). Quantification of
      IEC proliferation revealed 208 (+) cells per high-power field (HPF) in breast-fed
      pups, which decreased significantly to 99 (+) cells per HPF in stressed pups and
      increased to 190 (+) cells per HPF in stressed pups treated with HB-EGF (P <
      .05). CONCLUSIONS: These results demonstrate that HB-EGF protects newborn rats
      from experimental NEC in a dose-dependent fashion. The ability of HB-EGF to
      protect the intestines from NEC is due, in part, to the ability of HB-EGF to
      preserve enterocyte migration and proliferation.

PMID- 17208570
TI  - Effect of subspecialty training on outcome after pediatric appendectomy.
AB  - BACKGROUND/PURPOSE: There have been few studies documenting the effect of
      subspecialty training on outcomes after appendectomy in children. Some studies
      have suggested a better outcome in patients managed by pediatric surgeons as
      compared with general surgeons. METHODS: We studied the effect of subspecialty
      training on clinical outcome and negative appendectomy rate after pediatric
      appendectomy. Children less than 19 years in Ontario who underwent appendectomy
      were identified. Outcomes were compared between pediatric and general surgeons.
      Subanalyses were conducted for the age groups 0 to 5, 6 to 12, and 13 to 18
      years. RESULTS: Over 8 years, 24,019 children underwent appendectomy with a
      preoperative diagnosis of appendicitis. Of these, 21,027 had appendicitis.
      General surgeons performed 81.2% of the operations. Negative appendectomy rates
      were 8.3% and 13.4% (P < .0001) in the pediatric and general surgeon groups,
      respectively. Children operated on by pediatric surgeons were younger (10.5 +/-
      3.6 vs 12.8 +/- 3.8; P < .05), more likely to be perforated (36.6% vs 32.0%; P <
      .0001), and had a longer postoperative stay (3.8 vs 3.0 days; P < .0001). There
      was no difference between groups with respect to wound infection or readmission
      rate when age and perforation status were accounted for. CONCLUSIONS: Pediatric
      surgeons performed significantly fewer negative appendectomies than general
      surgeons. Although pediatric surgeons kept their patients longer in the hospital,
      their patients' wound infection and readmission rates were not different from
      that of the patients of general surgeons.

PMID- 17208571
TI  - Outcome of excision of megarectum in children with anorectal malformation.
AB  - BACKGROUND/PURPOSE: Megarectum in association with anorectal malformation
      contributes to chronic constipation and fecal incontinence. Resection of
      megarectum in anorectal malformation improves bowel function, but neuropathy and
      poor sphincter quality may affect the outcome of fecal continence adversely. The
      aim of this study was to evaluate the benefits of resection of megarectum in
      anorectal malformation and to ascertain the impact of anal sphincter quality and
      neuropathy on the outcome. METHODS: We studied 62 children with intractable fecal
      incontinence after repair of anorectal malformation between January 1991 and
      January 2005. All patients were investigated with anorectal manometry and anal
      endosonography under ketamine anesthesia. On endosonography, an intact or scarred
      internal anal sphincter (IAS) was classified as good and a fragmented or absent
      IAS as poor. On manometry, a resting anal sphincter pressure equal to or more
      than 30 mm Hg was classified as good and a lower pressure as poor. Functional
      assessment of fecal continence was done before and after excision of megarectum
      using a modified Wingfield scores. RESULTS: Sixteen children had excision of
      megarectum with median age of 9 years (range, 2-15 years) and postoperative
      follow-up of 5 years (range, 1-10 years). Seven had formation of antegrade
      continent enema stoma before excision of megarectum. Children were classified
      into three groups of anomalies: low (n = 6), intermediate (n = 4), and high (n =
      6). All children were incontinent of feces. After excision of megarectum, of the
      9 children with good IAS and no neuropathy, 7 became continent of feces. Of the
      remaining 7 children, 4 had poor IAS and 3 had neuropathy, 5 of whom required an
      antegrade continent enema stoma to be clean. CONCLUSION: Excision of megarectum
      in children who had previous repair of anorectal malformation results in fecal
      continence in the presence of a good IAS and absence of neuropathy. Patients with
      a poor IAS or neuropathy will often require artificial means of fecal continence.

PMID- 17208572
TI  - Fast-track surgery in infants and children.
AB  - BACKGROUND/PURPOSE: Fast-track surgery is not well established for infants and
      children. The aim of our prospective study was to investigate the feasibility of
      fast-track concepts for pediatric surgical procedures including laparoscopic
      techniques. METHODS: Fast-track concepts, including immediate postoperative
      feeding, immediate mobilization, and morphine sparing pain treatment, were
      established for pyeloplasty, appendectomy, bowel anastomosis, fundoplication,
      hypospadia repair, and full/partial nephrectomy. All consecutive patients
      undergoing these procedures were prospectively investigated from June 2004 to
      June 2005. Patients with additional relevant diseases, reoperation, and
      perforated appendicitis were excluded from fast-track treatment. The length of
      hospital stay was compared with data derived from the German reimbursement system
      with German diagnosis-related groups for patients with a similar case mix index
      and hospitals with a similar structure. RESULTS: Of a total of 159 patients (mean
      age, 5.8 +/- 5.3 years), 113 (71%) were finally treated according to the fast
      track protocols. There were no complications associated with fast-track surgery.
      The intensity of pain during the immediate postoperative period was higher than 5
      on a 10-point scale in children older than 4 years. Analgesia was excellent at
      all other time points. The mean hospital stay of fast-track patients was 2.3 +/-
      1 days and was significantly shorter (P < .01) compared with German diagnosis
      related group data for all procedures (pyeloplasty, 1.9 +/- 0.9 vs 12.2 +/- 0.2;
      nephrectomy, 1.9 +/- 1.0 vs 14.4 +/- 2.8; bowel anastomosis, 3.2 +/- 0.6 vs 12.9
      +/- 2.4; fundoplication, 3.2 +/- 0.8 vs 15.2 +/- 4.2; appendectomy, 3.7 +/- 2.4
      vs 6.3 +/- 1.8; hypospadia repair, 2.1 +/- 1 vs 8.4 +/- 1.4). Two readmissions
      were recorded. Ninety-six percent of patients and parents scored the fast-track
      concepts as excellent. CONCLUSION: The feasibility of fast-track concepts in
      children is excellent, with short duration of hospitalization and high comfort.

PMID- 17208573
TI  - Kidney development in the nitrofen-induced pulmonary hypoplasia and congenital
      diaphragmatic hernia in rats.
AB  - BACKGROUND/PURPOSE: The relationship of the developing lung and kidney is not
      completely understood. Renal enlargement has been reported in association with
      pulmonary hypoplasia in congenital diaphragmatic hernia (CDH). Recent studies
      suggest that retinoids may be involved in the pathogenesis of CDH. The aims of
      this study were to investigate the effects of pulmonary hypoplasia on renal
      development and to evaluate retinoids status of kidneys in the nitrofen model of
      CDH. METHODS: Pregnant rats were exposed to either olive oil or 100 mg of
      nitrofen on day 9.5 of gestation. Fetuses were recovered at term and divided into
      3 groups: 1, control (n = 69); 2, nitrofen without CDH (n = 25); and 3, nitrofen
      with CDH (n = 40). Kidneys were dissected, weighed, and processed for biochemical
      measurements of DNA, proteins, total retinol content, and for immunohistochemical
      staining of proliferating cells. RESULTS: Kidneys were smaller in nitrofen
      exposed animals vs control animals (group 3, 0.65 +/- 0.08; group 2, 0.62 +/-
      0.09 vs group 1, 0.73 +/- 0.09% of body weight, P < .001), and there were no
      differences between right and left kidney weight in all the 3 groups. Regression
      of total kidney weight on body weight showed a linear direct correlation between
      them in all the groups. Total amount of DNA was significantly reduced in nitrofen
      exposed animals vs controls (group 3, 80.58 +/- 35.65; group 2, 64.71 +/- 20.28
      vs group 1, 110.34 +/- 42.15 microg, P < .01), but the DNA concentration remained
      the same in the 3 groups (group 3, 3.59 +/- 1.26; group 2, 3.06 +/- 1.19; group
      1, 3.43 +/- 1.05 microg DNA/mg kidney). Total protein content (group 3, 1145.59
      +/- 500.36; group 2, 993.2 +/- 276.62; group 1, 1287.48 +/- 312.52 microg),
      protein concentration (group 3, 49.76 +/- 11.12; group 2, 43.95 +/- 6.79; group
      1, 47.38 +/- 6.93 microg protein/mg kidney), and protein-to-DNA ratio (group 3,
      15.12 +/- 5.98; group 2, 16.22 +/- 6.85; group I, 16.16 +/- 7.02 microg/microg)
      were similar in all groups. Retinol concentration was significantly reduced in
      both nitrofen-exposed groups compared with the control group (group 3, 1.35 +/-
      0.24; group 2, 1.28 +/- 0.11; group 1, 2.53+/-0.61 microg retinol/g kidney).
      Proliferation index was similar in all 3 groups (group 3, 50.43 +/- 8.81; group
      2, 47.96 +/- 6.01; group 1, 47.64 +/- 5.76% of proliferating cells). CONCLUSIONS:
      Our data clearly show that renal enlargement in association with pulmonary
      hypoplasia is not seen in the nitrofen-induced CDH. These results rule out any
      possible relationship between lung and kidney development. Moreover, kidneys are
      hypoplastic in both nitrofen-exposed groups and have reduced retinol content,
      suggesting that a retinoid pathway disruption could be the common mechanism in
      the pathogenesis of lung and kidney hypoplasia in the nitrofen model of CDH.

PMID- 17208574
TI  - Carbon dioxide suppresses macrophage superoxide anion production independent of
      extracellular pH and mitochondrial activity.
AB  - BACKGROUND: Superoxide anions released by activated macrophages during surgery
      are considered to be responsible for local cellular damage. Application of CO2
      pneumoperitoneum during laparoscopy affects superoxide anion release, but the
      underlying mechanism remains unclear and the data reported are conflicting. We
      investigated the direct and pH-mediated impact of CO2 and air on macrophage
      superoxide anion production. METHODS: Cells of the NR 8383 rat macrophage cell
      line were incubated for 2 hours in 5% CO2, 100% CO2, and room air or pH 7.4, pH
      6.5, and pH 5.5. The extracellular pH was monitored during incubation. At 0, 2,
      and 6 hours after incubation, the release of superoxide anions was determined
      fluorometrically. The mitochondrial activity was determined via the conversion of
      MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] during and
      after incubation. RESULTS: Extracellular pH decreased to 6.4 during incubation in
      a CO2 atmosphere. The release of superoxide anions was significantly reduced
      immediately after CO2 incubation. It was restored at all other time-points.
      Decreasing the extracellular pH to 6.5 had no effect on superoxide anion release,
      whereas acidification of the extracellular milieu to pH 5.5 significantly
      suppressed subsequent superoxide release. Mitochondrial activity was
      significantly decreased by CO2 up to 2 hours and by acidic milieu up to 6 hours.
      Incubation in room air had no effect. CONCLUSIONS: Incubation in CO2 can directly
      suppress macrophage superoxide anion production. This effect is of short
      duration, fully reversible, and not correlated to changes in extracellular pH or
      mitochondrial activity. Air contamination does not affect macrophage superoxide
      anion release. We speculate that CO2 pneumoperitoneum could attenuate the
      intraoperative free radical production by directly inhibiting superoxide anion
      release of macrophages without long-lasting suppression of macrophages and their
      capacity to release superoxide anions postoperatively.

PMID- 17208575
TI  - Historic milestones of Hirschsprung's disease (commemorating the 90th anniversary
      of Professor Harald Hirschsprung's death).

PMID- 17208576
TI  - Prosthetic esophageal erosion after mesh hiatoplasty in a child, removed by
      transabdominal endogastric surgery.
AB  - Although there is evidence in the adult surgical literature to suggests that the
      use of mesh prosthesis during laparoscopic hiatal hernia repair results in much
      reduced recurrence rates, there remains a real potential for esophageal and
      gastric mesh erosion. A 12-year-old boy presented with esophageal obstruction
      from an eroded polytetrafluoroethylene prosthesis used to buttress a hiatal
      hernia repair 9 years earlier. A laparoscopic endogastric approach was used to
      remove the mesh. Great caution must be exercised in the decision to use mesh for
      hiatal hernia repair in children who must live with such a prosthesis for a
      lifetime and risk erosion. Mesh should be reserved only for those children who
      have extremely large defects with no chance of primary closure and for those with
      recurrent hernias and friable crural tissue. In all cases, the family must be
      informed of the potential for eventual erosion. Removal of eroded mesh using
      minimal access techniques can be simple and effective.

PMID- 17208577
TI  - Severe congenital midureteral dilatation.
AB  - Congenital midureteral stricture is an uncommon cause of prenatal hydronephrosis,
      and it is generally associated with proximal hydroureteronephrosis . We report a
      unique case of a congenital severe midureteral dilatation associated with mild
      proximal ureteral dilatation and normal distal ureteral diameter. The dilated
      midureter was excised, and an open end-to-end ureteroureterostomy was performed.
      Follow-up 6 months after surgical correction revealed marked improvement in the
      left-sided hydronephrosis and complete resolution of the hydroureter.

PMID- 17208578
TI  - Octreotide improved the quality of life in a child with malignant bowel
      obstruction caused by peritoneal dissemination of colon cancer.
AB  - This is a first pediatric case about the efficacy of octreotide for improving
      symptoms of malignant bowel obstruction. A 12-year-old boy was referred to our
      hospital for treatment of transverse colon cancer with peritoneal dissemination.
      A transverse colectomy was undertaken with postoperative adjuvant chemotherapy.
      Seven months later, severe abdominal symptoms occurred caused by incomplete bowel
      obstruction owing to tumor progression. The patient's quality of life decreased
      with a resultant disturbed mental condition. His parents sought to stop
      chemotherapy and for him to receive palliative care at home. We suggested
      nasogastric tube placement, but this was rejected. After obtaining informed
      consent, octreotide was administered intravenously. After 1 week, abdominal
      symptoms improved and the boy's complaints stopped. He had a good appetite and
      was able to eat small amounts of food. He was able to spend his final 2 months at
      home without nausea and in his family surroundings.

PMID- 17208579
TI  - Streptococcal pancreatitis and toxic shock syndrome in a 2-month-old infant.
AB  - The rare clinical scenario of an infant with group A streptococcal pancreatitis
      associated with toxic shock syndrome is reported. The presentation, evaluation,
      and management of this unusual clinical entity are discussed.

PMID- 17208580
TI  - Gallstone ileus 20 years after a Kasai procedure using a stapled antireflux
      valve.
AB  - We present a case of intestinal obstruction owing to a gallstone ileus in a
      patient 20 years after a Kasai procedure for biliary atresia in which a stapled
      antireflux valve was constructed to treat recurrent cholangitis. The etiology of
      this rare presentation is discussed.

PMID- 17208581
TI  - Calcific parasite or surgical miscellany?
AB  - This article highlights the difficulties posed by initial radiological
      investigations that misleadingly interpreted a linear opacity in the ascending
      colon of a 2-year-old to be a complicating calcified Ascaris. Final surgical
      management revealed an unusual cause for the tram tracking effect so
      pathognomonic of Ascaris infestation. Of interest are the images of the abdominal
      x-ray, ultrasound scan, and barium study.

PMID- 17208583
TI  - Severe asthma: lessons from the Severe Asthma Research Program.
AB  - Severe asthma affects only a small percentage of the asthma population. However,
      these patients remain poorly understood and difficult to treat. Because the
      numbers are relatively small (10% or less of the asthma population), a network
      approach with shared protocols, samples, and data provides a unique opportunity
      to recruit the numbers of subjects necessary to perform adequately powered
      studies. The Severe Asthma Network (Severe Asthma Research Program) was
      established by the National Heart, Lung, and Blood Institute in 2001 to advance
      collectively the study of severe asthma to determine factors that differentiated
      these patients or subjects from those with milder asthma. Nearly 800 subjects
      have been recruited in less than 4 years to begin to address these differences.
      Future studies will specifically evaluate the role of inflammatory/oxidative
      processes, infection, genetics, and the distal lung in the pathogenesis of severe
      asthma.

PMID- 17208584
TI  - A view from the bus: on the roadmap with the National Institutes of Health Asthma
      Networks.

PMID- 17208585
TI  - Addressing issues of asthma in inner-city children.
AB  - For children living in the inner city, asthma tends to be more frequent and
      severe. Although the causes for this heightened severity of asthma are not
      clearly established, environmental allergens likely play a major role. To
      characterize, understand, and treat children with asthma living in the inner city
      better, the National Institutes of Allergy and Infectious Diseases of the
      National Institutes of Health established an Inner City Asthma Program in 1991.
      Over the past 15 years, 3 separate inner-city asthma research networks have been
      formed and funded by this institute. The work from these programs has led to
      important observations including evidence that environmental allergens,
      particularly cockroach, are important for sensitization and severity of asthma of
      the affected children. Furthermore, reductions in the allergen load can lead to
      improved asthma control. The most recent program, the Inner City Asthma
      Consortium, was formed in 2002 with a goal to develop immune-based therapy for
      children with asthma in the inner city and to determine mechanisms of these
      therapies as well as immunopathogenesis of asthma in these high-risk children.
      This article reviews these programs and how they have begun the effort to
      understand and treat children with asthma who live in inner cities better and
      what their findings mean in relationship to unique features of asthma in inner
      city children.

PMID- 17208586
TI  - Interrelationships of quantitative asthma-related phenotypes in the
      Epidemiological Study on the Genetics and Environment of Asthma, Bronchial
      Hyperresponsiveness, and Atopy.
AB  - BACKGROUND: Delineating asthma subphenotypes is of interest to understand the
      cause of the disease. Few studies have addressed the interrelationships of
      quantitative asthma-related traits. OBJECTIVE: We sought to study the
      interrelationships of allergy markers and FEV(1) in relation to asthma and sex in
      children and adults. METHODS: Total IgE levels, skin prick test (SPT) positivity,
      eosinophil counts, and FEV(1) were assessed in 299 asthmatic cases (children and
      adults) recruited in chest clinics and 309 nonasthmatic population-based control
      subjects in the French Epidemiological Study on the Genetics and Environment of
      Asthma, Bronchial Hyperresponsiveness, and Atopy. RESULTS: Allergy parameters
      were significantly higher in asthmatic cases than in control subjects for
      children and adults and for both sexes. Sex and age modified the pattern of
      concordance of high IgE levels, SPT positivity, and eosinophilia among asthmatic
      cases, with the greatest overlap in male children (64%) and the lowest in male
      adults (18%). Patterns of change over the lifespan of IgE levels, eosinophil
      counts, and FEV(1)/height(2) varied, with the acceleration of FEV(1) decrease
      being particularly evident in asthmatic adults. In adult cases and control
      subjects, SPT positivity (particularly to indoor allergens) was significantly
      related to IgE levels but not to eosinophil counts. The association of eosinophil
      counts with IgE levels was evident only in children. Environmental factors
      (smoking, pets, and country living) did not alter the patterns observed.
      CONCLUSIONS: Each allergy-related phenotype showed a distinct relation with
      asthma, with the role for eosinophils being different than that for IgE levels
      and SPT responses. CLINICAL IMPLICATIONS: Taking age and sex into account is
      essential for understanding the interrelationships of the various allergy-related
      phenotypes to asthma status.

PMID- 17208587
TI  - The Predicting Response to Inhaled Corticosteroid Efficacy (PRICE) trial.
AB  - BACKGROUND: Although guidelines recommend anti-inflammatory therapy for
      persistent asthma, recent studies suggest that 25% to 35% of patients with asthma
      may not improve lung function with inhaled corticosteroids. OBJECTIVE: To
      evaluate potential biomarkers of predicting short-term (6-week) response to
      inhaled corticosteroid with subsequent evaluation of responders and nonresponders
      to asthma control over a longer interval (16 additional weeks). METHODS: Eighty
      three subjects with asthma off steroid were enrolled in this multicenter study.
      Biomarkers and asthma characteristics were evaluated as predictors of inhaled
      corticosteroid response over a 6-week trial for changes in FEV(1) and
      methacholine PC(20). After this, an additional 4-month trial evaluated asthma
      control. RESULTS: Although multiple baseline predictors had significant
      correlations with improvements for short-term inhaled steroid success, the only
      strong correlations (r >or= +/- 0.6) were albuterol reversibility (r = 0.83; P <
      .001), FEV(1)/forced vital capacity (r = -0.75; P < .001), and FEV(1) % predicted
      (r = -0.71; P < .001). Dividing the subjects in the short-term inhaled steroid
      trial into responders (>5% FEV(1) improvement) and nonresponders (<or=5%)
      determined the longer-term need for steroids. For the nonresponders, asthma
      control remained unchanged whether inhaled corticosteroids were continued or were
      substituted with a placebo (P = .99). The good short-term responders maintained
      asthma control longer-term only if maintained on inhaled steroids (P = .007).
      CONCLUSION: The short-term response to inhaled corticosteroids with regard to
      FEV(1) improvement predicts long-term asthma control. CLINICAL IMPLICATIONS: The
      decision to use long-term inhaled steroids could be based on a short-term trial.
      Different therapeutic strategies would need to be established for nonresponders.

PMID- 17208588
TI  - Predictors of cord blood IgE levels in children at risk for asthma and atopy.
AB  - BACKGROUND: Increased cord blood IgE levels, in conjunction with a family history
      of atopy, are associated with the development of allergic diseases in children.
      However, little is known about predictors of cord blood IgE levels. OBJECTIVE:
      Our objective was to identify predictors of cord blood IgE levels among infants
      at increased risk of atopy. METHODS: Cord blood IgE levels were measured in 874
      infants who were screened for participation in a birth cohort. Questionnaires
      were administered after birth of the infant, and maternal and cord blood was
      obtained for measurement of IgE levels. Logistic and tobit regression models were
      used to study the association between perinatal factors and cord blood IgE
      levels. RESULTS: In multivariable models infant male sex, increased maternal
      total IgE level, maternal allergen sensitization, Hispanic ethnicity, and
      residence in low-income areas were associated with detectable or increased cord
      blood IgE levels, whereas increasing maternal age was associated with
      undetectable or lower cord blood IgE levels. Although maternal smoking during
      pregnancy was positively associated with cord blood IgE levels in univariable
      models, the effect did not persist after adjusting for potential confounders.
      CONCLUSION: Maternal allergen sensitization, markers of socioeconomic
      disadvantage and race/ethnicity, maternal age, and infant sex might influence
      fetal production of IgE. We found no association of maternal parity, mode of
      delivery, gestational age, or season of birth with cord blood IgE levels.
      CLINICAL IMPLICATIONS: The identification of these definable familial and
      environmental factors that predict cord blood IgE levels might help in the early
      detection of infants at risk for atopic disorders.

PMID- 17208589
TI  - Downregulation of a disintegrin and metalloproteinase 33 by IFN-gamma in human
      airway smooth muscle cells.
AB  - BACKGROUND: A disintegrin and metalloproteinase 33 (ADAM33) has been identified
      as a susceptibility gene for asthma. ADAM33 is expressed in airway smooth muscle
      (ASM) cells and is suggested to play a role in the function of these cells.
      However, there is little information on the regulation of ADAM33. OBJECTIVE: To
      investigate whether ADAM33 is more highly expressed in ASM cells of patients with
      asthma than in those of normal subjects, and whether there is any inflammatory
      mediator (asthma-related cytokine/chemokine) that could modulate the expression
      of ADAM33 in ASM cells. METHOD: smRNA and protein expression of ADAM33 in
      bronchial biopsy specimens was investigated (in situ hybridization and
      immunohistochemistry). Effects of cytokines on expression of ADAM33 in cultured
      human ASM cells were evaluated by measuring mRNA (real-time RT-PCR) and protein
      (Western blotting). RESULTS: ADAM33 mRNA and protein in biopsied specimens were
      more highly expressed in ASM cells of patients with asthma than in cells of
      normal subjects. Cultured ASM cells expressed ADAM33 at both the mRNA and the
      protein levels. IFN-gamma reduced the mRNA expression dose-dependently and time
      dependently, whereas IL-4 and IL-13 or chemokines did not affect the expression.
      The reduction by IFN-gamma was partially restored by U0126, inhibitor for mitogen
      activated protein kinase kinase 1/2, suggesting a role for extracellular signal
      regulated kinase pathway. Further studies using cycloheximide and actinomycin-D
      suggested that the downregulation was at the transcriptional level. CONCLUSION:
      The expression of ADAM33 by ASM cells is increased in patients with asthma, and
      its expression may be regulated by IFN-gamma. CLINICAL IMPLICATIONS: IFN-gamma
      might have a role in suppressing ADAM33 in ASM cells.

PMID- 17208590
TI  - Disease-specific expression and regulation of CCAAT/enhancer-binding proteins in
      asthma and chronic obstructive pulmonary disease.
AB  - BACKGROUND: CCAAT/enhancer-binding proteins (C/EBPs) control cell proliferation;
      lack of C/EBPalpha correlates with increased proliferation of bronchial smooth
      muscle cells (BSMCs) of asthmatic patients. OBJECTIVE: We sought to assess
      disease-specific expression of C/EBPalpha, beta, delta, and epsilon and the
      effects of budesonide (10(-8) mol/L) and formoterol (10(-8) mol/L). METHODS:
      Expression and function of C/EBPalpha, beta, delta, and epsilon BSMCs of control
      subjects (n = 9), asthmatic patients (n = 12), and patients with chronic
      obstructive pulmonary disease (COPD; n = 10) were determined. RESULTS: The
      control group expressed C/EBPalpha, beta, delta, and epsilon, which were
      upregulated by serum (5%). Budesonide completely inhibited C/EBPalpha and beta
      expression; formoterol increased C/EBPalpha expression (2-fold). C/EBPdelta and
      epsilon expression were not affected by the drugs. The asthmatic group did not
      appropriately express C/EBPalpha. Basal levels of C/EBPbeta, delta, and epsilon
      were upregulated by serum (5%). Budesonide and formoterol increased C/EBPbeta
      levels (3.4-fold and 2.5-fold, respectively), leaving C/EBPalpha, delta, and
      epsilon levels unaffected. The COPD group normally expressed C/EBPalpha, beta,
      and epsilon, which were upregulated by serum treatment (5%). Basal levels of
      C/EBPdelta were downregulated by serum in 7 of 10 BSMC lines. Budesonide
      inhibited C/EBPalpha and beta expression, upregulated C/EBPdelta (3.2-fold), and
      had no effect on C/EBPepsilon. Formoterol upregulated C/EBPalpha expression (3
      fold) but not the other C/EBPs. Protein analysis and electrophoretic mobility
      shift assay confirmed the disease-specific expression pattern of C/EBPalpha in
      asthmatic patients and C/EBPdelta in patients with COPD. CONCLUSIONS: The
      expression and regulation of C/EBPs in BSMCs of asthmatic patients and patients
      with COPD seems disease specific. Budesonide and formoterol modulate C/EBP
      expression in a drug- and disease-specific pattern. CLINICAL IMPLICATIONS: The
      data could provide a method to discriminate between asthma and COPD at an early
      disease stage.

PMID- 17208591
TI  - S100A12 provokes mast cell activation: a potential amplification pathway in
      asthma and innate immunity.
AB  - BACKGROUND: The calcium-binding protein S100A12 might provoke inflammation and
      monocyte recruitment through the receptor for advanced glycation end products.
      OBJECTIVE: Because inflammation elicited by S100A12 in vivo had characteristics
      of mast cell (MC) activation, we aimed to define the mechanism. METHODS: Various
      MC populations were used to test S100A12 activation assessed on the basis of
      morphology, histamine release, leukotriene production, and cytokine induction. MC
      dependence of S100A12-provoked inflammation was tested in mice and on the rat
      microcirculation by means of intravital microscopy. Immunohistochemistry
      localized S100A12 in the asthmatic lung, and levels in sputum from asthmatic
      patients were quantitated by means of ELISA. Expression of the receptor for
      advanced glycation end products was evaluated by means of RT-PCR and Western
      blotting. RESULTS: S100A12 provoked degranulation of mucosal and tissue MCs in
      vitro and in vivo and amplified IgE-mediated responses. It induced a cytokine
      profile indicating a role in innate/T(H)1-mediated responses. S100A12-induced
      edema and leukocyte rolling, adhesion, and transmigration in the microcirculation
      were MC dependent. Eosinophils in airway tissue from asthmatic patients were
      S100A12 positive, and levels were increased in sputum. S100A12 responses were
      partially blocked by an antagonist to the receptor for advanced glycation end
      products, but MCs did not express mRNA or protein, suggesting an alternate
      receptor. CONCLUSION: This novel pathway highlights the potential importance of
      S100A12 in allergic responses and in infectious and chronic inflammatory
      diseases. CLINICAL IMPLICATIONS: MC activation by S100A12 might exacerbate
      allergic inflammation and asthma. S100A12 might provide a novel marker for
      eosinophilic asthma.

PMID- 17208592
TI  - The anti-inflammatory effect of glucocorticoids is mediated by glucocorticoid
      induced leucine zipper in epithelial cells.
AB  - BACKGROUND: Nuclear factor kappaB (NF-kappaB) plays a key role in the
      pathogenesis of asthma, being linked to the production of inflammatory cytokines
      that drive inflammation. A recently described anti-inflammatory protein,
      glucocorticoid-induced leucine zipper (GILZ), interferes with NF-kappaB-mediated
      gene transcription in T cells and macrophages. OBJECTIVE: We sought to analyze
      the regulation of GILZ expression in airway epithelial cells and determine
      whether GILZ mediates part of the anti-inflammatory effect of corticosteroids.
      METHODS: GILZ expression was assessed by means of PCR and immunoblotting in human
      epithelial cells at baseline and after stimulation with dexamethasone or
      cytokines (IL-1beta, TNF-alpha, and IFN-gamma). The effect of GILZ on LPS-, IL
      1beta-, and polyinosinic:polycytidylic acid-induced NF-kappaB activation was
      assessed in BEAS-2B cells overexpressing GILZ. The requirement for GILZ in the
      inhibitory action of dexamethasone was assessed by knocking down GILZ expression
      by means of small interfering RNA (siRNA) technology. RESULTS: GILZ is
      constitutively expressed by human airway epithelial cells, and its levels are
      increased by dexamethasone and decreased by inflammatory cytokines.
      Overexpression of GILZ in BEAS-2B cells significantly inhibited the ability of IL
      1beta, LPS, and polyinosinic:polycytidylic acid to activate NF-kappaB, whereas
      knockdown of GILZ inhibited the ability of dexamethasone to suppress IL-1beta
      induced chemokine expression. CONCLUSION: This study demonstrates the expression
      of GILZ in human airway epithelial cells, its induction by dexamethasone, its
      suppression by inflammatory cytokines, and its role in mediating the anti
      inflammatory effects of dexamethasone. CLINICAL IMPLICATIONS: Therapeutic
      upregulation of GILZ may be a novel strategy for the treatment of asthma.

PMID- 17208593
TI  - Src homology 2 domain-containing inositol 5-phosphatase 1 deficiency leads to a
      spontaneous allergic inflammation in the murine lung.
AB  - BACKGROUND: Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP-1)
      controls the intracellular level of the phosphoinositide 3-kinase product
      phosphotidylinositol-3,4,5-trisphosphate and functions as a negative regulator of
      cytokine and immune receptor signaling. Emerging evidence suggests that the
      phosphoinositide 3-kinase pathway might be involved in allergic inflammation in
      the lung. However, the functional relevance of SHIP-1 in the T(H)2 activation
      pathway has not been established. SHIP-1(-/-) mice have spontaneous
      myeloproliferative inflammation in the lung, the nature of which has not been
      elucidated. We hypothesized that SHIP-1 plays an important role as a regulator in
      pulmonary allergic inflammation and in maintaining lung homeostasis. OBJECTIVE:
      To test our hypothesis, we characterized the pulmonary phenotype of SHIP-1(-/-)
      mice. RESULTS: Analyses of lung histopathology and bronchoalveolar lavage
      cellularity revealed that the majority of SHIP-1(-/-) mice had progressive and
      severe pulmonary inflammation of macrophages, lymphocytes, neutrophils, and
      eosinophils; mucous hyperplasia; airway epithelial hypertrophy; and subepithelial
      fibrosis. These pathologic changes were accompanied by exaggerated production of
      T(H)2 cytokines and chemokines, including IL-4, IL-13, eotaxin, and monocyte
      chemoattractant protein 1, in the lung. Furthermore, the number of mast cells
      significantly increased, and many of these cells were undergoing degranulation,
      which was correlated with increased content and spontaneous release of histamine
      in the lung tissue of SHIP-1(-/-) mice. CONCLUSION: These findings provide strong
      evidence that mice lacking SHIP-1 have an allergic inflammation in the lung,
      suggesting that SHIP-1 plays an important role in regulating the T(H)2 signaling
      pathway and in maintaining lung homeostasis. CLINICAL IMPLICATIONS: SHIP-1 as a
      regulator might be a potential therapeutic target for controlling allergic
      inflammation in diseases such as asthma.

PMID- 17208594
TI  - Cysteinyl leukotrienes synergize with growth factors to induce proliferation of
      human bronchial fibroblasts.
AB  - BACKGROUND: Cysteinyl leukotrienes (cys-LTs) are potent asthma-related mediators
      that function through their G protein-coupled receptors, cys-LT receptor type 1
      (CysLT1R) and cys-LT receptor type 2 (CysLT2R). OBJECTIVE: Because many G protein
      coupled receptors transactivate the epidermal growth factor receptor (EGFR)
      through metalloprotease-mediated ligand shedding, we investigated the effects of
      cys-LTs on signal transduction and proliferation of bronchial fibroblasts.
      METHODS: Human bronchial fibroblasts were grown from biopsy specimens of healthy
      subjects. Mitogenesis was assessed on the basis of tritiated methylthymidine
      incorporation. RESULTS: Leukotriene (LT) D(4) alone did not increase mitogenesis
      but dose-dependently increased thymidine incorporation and cell proliferation in
      the presence of epidermal growth factor (EGF). The enhancement was not prevented
      by CysLT1R antagonists (MK-571 and montelukast) or by a dual antagonist (BAY
      u9773), which is consistent with the lack of detectable mRNA for CysLT1R and
      CysLT2R in bronchial fibroblasts. LTD(4) did not cause EGFR transphosphorylation
      nor was the synergism blocked by the metalloprotease inhibitor GM6001. The EGFR
      selective kinase inhibitor AG1478 suppressed the synergy between LTD(4) and EGF
      but had no effect on synergistic interactions of LTD(4) with other receptor
      tyrosine kinase growth factors. The effect of LTD(4) involved a pertussis toxin
      sensitive and protein kinase C-mediated intracellular pathway, leading to
      sustained growth factor-dependent phosphorylation of extracellular signal
      regulated kinase 1/2 and protein kinase B (PKB/Akt). CONCLUSION: Cys-LTs do not
      transactivate EGFR but have a broader capability to synergize with receptor
      tyrosine kinase pathways. CLINICAL IMPLICATIONS: This study implies a critical
      role of cys-LTs in airway fibrosis in asthma and other chronic airway diseases,
      which might not be blocked by therapy with current LT receptor antagonists.

PMID- 17208595
TI  - Cysteinyl leukotriene upregulates IL-11 expression in allergic airway disease of
      mice.
AB  - BACKGROUND: Chronic airway inflammation and airway remodeling are important
      features of bronchial asthma. IL-11 is one of the important mediators involved in
      the process of airway inflammation and remodeling. Cysteinyl leukotrienes
      (cysLTs) play roles in recruitment of inflammatory cells, airway smooth muscle
      contraction, vascular leakage, increased mucus secretion, decreased mucociliary
      clearance, and airway fibrosis. OBJECTIVE: An aim of the present study was to
      determine the effect of the cysLTs on the regulation of IL-11 expression.
      METHODS: We used a C57BL/6 mouse model of allergic airway disease and murine
      tracheal epithelial cells to examine the effects of cysLTs on the regulation of
      IL-11 expression. RESULTS: Our present study with an ovalbumin-induced murine
      model of allergic airway disease revealed that levels of leukotriene C(4)
      (LTC(4)) in bronchoalveolar lavage fluids were increased and that administration
      of montelukast or pranlukast reduced the increased levels of LTC(4); the
      increased expression of IL-11 protein and mRNA in lung tissues; airway
      inflammation, bronchial hyperresponsiveness; the increased levels of TGF-beta(1),
      IL-4, and IL-13 in bronchoalveolar lavage fluids and lung tissues; and airway
      fibrosis. In addition, LTC(4) stimulates epithelial cells to produce IL-11. Our
      results also showed that cysLT type 1 receptor antagonists downregulated the
      activity of a transcription factor, nuclear factor kappaB, and BAY 11-7085
      substantially reduced the increased levels of IL-11 after ovalbumin inhalation.
      CONCLUSION: These results suggest that cysLTs regulate the IL-11 expression in
      allergic airway disease. CLINICAL IMPLICATIONS: These findings provide one of the
      molecular mechanisms for the effects of cysLTs on airway inflammation and
      fibrosis in allergic airway diseases.

PMID- 17208596
TI  - Respiratory illnesses in early life and asthma and atopy in childhood.
AB  - BACKGROUND: The relation between respiratory illnesses in early life and the
      development of asthma and atopy in childhood is incompletely understood.
      OBJECTIVE: We sought to examine the relationship between respiratory illnesses in
      early life and atopic diseases at school age. METHODS: We performed a prospective
      birth cohort study of the relationship between respiratory illnesses in the first
      year of life and asthma, atopy (sensitization to >or=1 allergen), and allergic
      rhinitis at school age in 440 children with a parental history of atopy. Logistic
      regression was used to examine the relationship between respiratory illnesses and
      asthma, atopy, and allergic rhinitis. The relationship between respiratory
      illnesses in early life and repeated measures of wheezing between the ages of 1
      and 7 years was investigated by using a proportional hazards models. RESULTS:
      Physician-diagnosed croup (adjusted odds ratio [OR], 0.30; 95% CI, 0.12-0.72) and
      having 2 or more physician-diagnosed ear infections (adjusted OR, 0.58; 95% CI,
      0.35-0.98) in the first year of life were inversely associated with atopy at
      school age. Physician-diagnosed bronchiolitis before age 1 year was significantly
      associated with asthma at age 7 years (adjusted OR, 2.77; 95% CI, 1.23-6.22).
      Recurrent nasal catarrh (>or=3 episodes of a runny nose) in the first year of
      life was associated with allergic rhinitis at age 7 years (adjusted OR, 2.99; 95%
      CI, 1.03-8.67). CONCLUSION: The relationship between early-life respiratory
      illnesses and asthma and atopy is complex and likely dependent on the type of
      infection and immune response it initiates. CLINICAL IMPLICATIONS: Certain
      respiratory illnesses in early life modify the risk of atopy and asthma at school
      age.

PMID- 17208597
TI  - Selection of aspirin dosages for aspirin desensitization treatment in patients
      with aspirin-exacerbated respiratory disease.
AB  - BACKGROUND: Aspirin desensitization followed by daily aspirin therapy is
      effective add-on treatment for patients with aspirin-exacerbated respiratory
      disease. Prior studies used 650 mg of aspirin twice daily, but studies at lower
      dosages were inconclusive. OBJECTIVE: We sought to determine the optimal daily
      dosage of aspirin treatment. METHODS: We studied 137 patients who had undergone
      successful aspirin desensitization and randomized them into 2 groups, 650 mg
      twice daily versus 325 mg twice daily. After 1 month, patients either increased
      or decreased their dosage based on their symptom control and continued that
      dosage for the remainder of the year. RESULTS: Patients taking either 650 mg
      twice daily or 325 mg twice daily showed significant improvements in number of
      sinus infections, sinus operations, and hospitalizations for asthma (all P <
      .0001). Anosmia, nasal/sinus symptoms, and asthma symptoms also improved in both
      groups (all P < .03). Systemic corticosteroid dosages decreased by 3- and 4-fold
      in the 325 mg twice daily and 650 mg twice daily groups, respectively. Of the 137
      patients, 32 had adverse effects from or discontinued aspirin therapy: 14 (44%)
      of 32 from the group randomized to taking 650 mg twice daily and 18 (56%) of 32
      from the group randomized to 325 mg twice daily. The most common adverse effect
      was dyspepsia. CONCLUSION: Both dosages were efficacious, and side effects
      occurred in both groups at similar frequencies. Some patients initially taking
      325 mg twice daily required an increase to 650 mg twice daily for optimal symptom
      control. CLINICAL IMPLICATIONS: We recommend that patients begin daily aspirin
      therapy with 650 mg twice daily and subsequently decrease to the lowest effective
      dosage (usually 325 mg twice daily).

PMID- 17208598
TI  - Race-ethnicity, crime, and other factors associated with adherence to inhaled
      corticosteroids.
AB  - BACKGROUND: Previous studies have shown differences in adherence to inhaled
      corticosteroids (ICSs) by race-ethnicity, yet little is known about factors that
      contribute to adherence within these groups. Environmental stressors, such as
      crime exposure, which has been associated with asthma morbidity, might also
      predict ICS adherence. OBJECTIVE: We sought to identify factors associated with
      ICS adherence among patients with asthma and among African American patients and
      white patients separately. METHODS: Study patients with asthma were aged 18 to 50
      years and were enrolled in a large southeast Michigan health maintenance
      organization between January 1, 1999, and December 31, 2001. The primary outcome,
      ICS adherence, was calculated by linking prescription-fill data with dosage
      information. Predictor variables included age, sex, race-ethnicity, measures of
      socioeconomic status (SES), average ICS copay, existing comorbidities, and crime
      rate in area of residence. RESULTS: Adherence information was available for 176
      patients. ICS adherence was lower among African American patients (n = 75) when
      compared with white patients (n = 94; 40% vs 58%, respectively; P = .002). Among
      white patients, adherence was significantly lower for women when compared with
      men. Among African American patients, age and residential crime rates were
      positively and negatively associated with ICS adherence, respectively. Area crime
      remained a predictor of adherence in African American patients, even after
      adjusting for multiple measures of SES. CONCLUSIONS: This study suggests that an
      environmental stressor, area crime, provides additional predictive insight into
      ICS-adherent behavior beyond typical SES factors. CLINICAL IMPLICATIONS: Better
      understanding of environmental factors that influence ICS adherence might aid in
      efforts to improve it.

PMID- 17208599
TI  - Histamine H4 receptor antagonists are superior to traditional antihistamines in
      the attenuation of experimental pruritus.
AB  - BACKGROUND: Histamine is a potent mediator of itch in humans, yet histamine H(1)
      receptor antagonists have been shown to be of limited use in the treatment of
      certain chronic pruritic diseases. The histamine H(4) receptor is a recently
      described histamine receptor, expressed on hematopoietic cells, linked to the
      pathology of allergy and asthma. OBJECTIVE: The contribution of the novel
      histamine H(4) receptor to histaminergic and allergic pruritus was investigated.
      RESULTS: Histamine and a selective histamine H(4) receptor agonist caused
      scratching responses in mice, which were almost completely attenuated in
      histamine H(4) receptor knockout mice or by pretreatment with the selective
      histamine H(4) receptor antagonist, JNJ 7777120. Pruritus induced by allergic
      mechanisms was also potently inhibited with histamine H(4) receptor antagonist
      treatment or in histamine H(4) receptor knockout mice. In all cases, the
      inhibitory effect of histamine H(4) receptor antagonist was greater than those
      observed with histamine H(1) receptor antagonists. The histamine H(4) receptor
      mediated pruritus was shown to be independent of mast cells or other
      hematopoietic cells and may result from actions on peripheral neurons.
      CONCLUSION: These results demonstrate that the histamine H(4) receptor is
      involved in pruritic responses in mice to a greater extent than the histamine
      H(1) receptor. CLINICAL IMPLICATIONS: Histamine H(4) receptor antagonists may
      have therapeutic utility for treating chronic pruritic diseases in humans where
      histamine H(1) receptor antagonists are not effective.

PMID- 17208600
TI  - Probiotic supplementation for the first 6 months of life fails to reduce the risk
      of atopic dermatitis and increases the risk of allergen sensitization in high
      risk children: a randomized controlled trial.
AB  - BACKGROUND: Despite preliminary evidence, the role of probiotics in allergy
      prevention is unclear. OBJECTIVE: To determine whether early probiotic
      supplementation prevents allergic disease in high-risk infants. METHODS: Newborns
      of women with allergy (n = 231) received either Lactobacillus acidophilus (LAVRI
      A1) or placebo daily for the first 6 months of life. Children were assessed for
      atopic dermatitis (AD) and other symptoms at 6 and 12 months and had allergen
      skin prick tests (SPT) at 12 months of age. RESULTS: A total of 178 infants
      completed the supplementation period. Those in the probiotic group showed
      significantly higher rates of Lactobacillus colonization (P = .039). At 6 months,
      AD rates were similar in the probiotic (n = 23/89; 25.8%) and placebo (n = 20/88;
      22.7%) groups (P = .629). There was also no difference at 12 months, although the
      proportion of children with SPT+AD was significantly higher in the probiotic
      group (P = .045). At 12 months, the rate of sensitization was significantly
      higher in the probiotic group (P = .030). The presence of culturable Lactobacilli
      or Bifidobacterium in stools in the first month of life was not associated with
      the risk of subsequent sensitization or disease; however, the presence of
      Lactobacillus at 6 months of age was associated with increased risk of subsequent
      cow's milk sensitization (P = .012). CONCLUSION: Early probiotic supplementation
      with L acidophilus did not reduce the risk of AD in high-risk infants and was
      associated with increased allergen sensitization in infants receiving
      supplements. The long-term significance of the increased rate of sensitization
      needs to be investigated in further studies. CLINICAL IMPLICATIONS: These
      findings challenge the role of probiotics in allergy prevention.

PMID- 17208601
TI  - Probiotics and prebiotic galacto-oligosaccharides in the prevention of allergic
      diseases: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: The increase in allergic diseases is attributed to a relative lack of
      microbial stimulation of the infantile gut immune system. Probiotics, live health
      promoting microbes, might offer such stimulation. OBJECTIVE: We studied the
      effect of a mixture of 4 probiotic bacterial strains along with prebiotic galacto
      oligosaccharides in preventing allergic diseases. METHODS: We randomized 1223
      pregnant women carrying high-risk children to use a probiotic preparation or a
      placebo for 2 to 4 weeks before delivery. Their infants received the same
      probiotics plus galacto-oligosaccharides (n = 461) or a placebo (n = 464) for 6
      months. At 2 years, we evaluated the cumulative incidence of allergic diseases
      (food allergy, eczema, asthma, and allergic rhinitis) and IgE sensitization
      (positive skin prick test response or serum antigen-specific IgE level >0.7
      kU/L). Fecal bacteria were analyzed during treatment and at age 2 years. RESULTS:
      Probiotic treatment compared with placebo showed no effect on the cumulative
      incidence of allergic diseases but tended to reduce IgE-associated (atopic)
      diseases (odds ratio [OR], 0.71; 95% CI, 0.50-1.00; P = .052). Probiotic
      treatment reduced eczema (OR, 0.74; 95% CI, 0.55-0.98; P = .035) and atopic
      eczema (OR, 0.66; 95% CI, 0.46-0.95; P = .025). Lactobacilli and bifidobacteria
      more frequently (P < .001) colonized the guts of supplemented infants.
      CONCLUSION: Probiotic treatment showed no effect on the incidence of all allergic
      diseases by age 2 years but significantly prevented eczema and especially atopic
      eczema. The results suggest an inverse association between atopic diseases and
      colonization of the gut by probiotics. CLINICAL IMPLICATIONS: The prevention of
      atopic eczema in high-risk infants is possible by modulating the infant's gut
      microbiota with probiotics and prebiotics.

PMID- 17208602
TI  - Egg oral immunotherapy in nonanaphylactic children with egg allergy.
AB  - BACKGROUND: There is no current active treatment for food allergy. Traditional
      injection immunotherapy has been proved unsafe, and thus there is a need for
      other forms of immunotherapy. OBJECTIVE: The purpose was to study the safety and
      immunologic effects of egg oral immunotherapy (OIT). The short-term goal was to
      desensitize subjects to protect against accidental ingestion reactions. The
      eventual goal was to induce lasting clinical and immunologic tolerance. METHODS:
      Subjects with a history of egg allergy but without a history of anaphylaxis to
      egg underwent a 24-month egg OIT protocol involving modified rush, build-up, and
      maintenance phases. Double-blind, placebo-controlled food challenges were
      performed at study conclusion. Egg-specific IgE and IgG concentrations were
      followed. RESULTS: Seven subjects completed the protocol. Egg-specific IgG
      concentrations increased significantly, whereas egg-specific IgE concentrations
      did not significantly change. Three subjects tolerated known or possible
      accidental egg ingestions while receiving OIT. During double-blind, placebo
      controlled food challenges at study conclusion, all tolerated significantly more
      egg protein than at study onset and than that found in the typical accidental
      exposure. Two subjects demonstrated oral tolerance. CONCLUSION: This study
      provides proof of concept that OIT can be safely used for patients with egg
      allergy without a history of anaphylaxis to egg. Egg OIT does not heighten
      sensitivity to egg and might protect against reaction on accidental ingestion.
      Whether OIT will induce clinical oral tolerance cannot be concluded from this
      initial cohort. CLINICAL IMPLICATIONS: Use of allergen-specific OIT to protect
      subjects with food allergy from reaction on accidental ingestion would represent
      a significant paradigm change in the treatment of food allergy.

PMID- 17208603
TI  - Esophageal remodeling in pediatric eosinophilic esophagitis.
AB  - BACKGROUND: Eosinophils are associated with airway remodeling in asthma, but
      studies have not yet determined whether eosinophilic esophagitis (EE) is
      associated with esophageal remodeling. OBJECTIVE: We performed quantitative
      immunohistochemical analysis of remodeling changes in esophageal biopsy specimens
      from children with and without EE to evaluate if there were changes in the
      esophagus of pediatric patients with EE akin to airway remodeling. In addition,
      we determined whether the esophagus of patients with EE had increased levels of
      expression of TGF-beta(1) and its signaling molecule, phosphorylated SMAD2/3
      (phospho-SMAD2/3). METHODS: To determine esophageal levels of eosinophilic
      inflammation, fibrosis, and vascular activation, endoscopically obtained
      esophageal biopsy specimens from 7 patients with EE (5 strictured, 2
      nonstrictured), 7 with gastroesophageal reflux disease, and 7 normal patients
      were processed for immunohistology, trichrome staining, and assessment of levels
      of expression of TGF-beta(1), phospho-SMAD2/3, and vascular cell adhesion
      molecule 1. RESULTS: Esophageal biopsies in patients with EE demonstrated
      increased levels of subepithelial fibrosis and increased expression of TGF
      beta(1) and its signaling molecule phospho-SMAD2/3 compared with gastroesophageal
      reflux disease and normal control patients. In addition, esophageal biopsies in
      patients with EE demonstrated an increased vascular density and an increased
      expression of the vascular endothelial adhesion molecule, vascular cell adhesion
      molecule 1. CONCLUSION: Previously unrecognized esophageal remodeling changes
      analogous to aspects of airway remodeling are detectable in the subepithelial
      region of the esophagus in pediatric patients with EE. CLINICAL IMPLICATIONS:
      Pediatric patients with EE demonstrate increased fibrosis, vascularity, and
      vascular activation in the esophagus that may contribute to stricture formation
      and potentially provide a basis for stratifying patients with EE on the basis of
      disease severity and/or prognosis.

PMID- 17208604
TI  - Class switch recombination to IgE in the bronchial mucosa of atopic and nonatopic
      patients with asthma.
AB  - BACKGROUND: Class switching from IgM/IgG/IgA to IgE is required for B cells to
      express IgE. This requires class switch recombination in the Ig heavy-chain gene
      locus. It is generally believed that class switch recombination occurs in
      lymphoid tissue, but it was recently shown that class switching to IgE occurs in
      the nasal mucosa in allergic rhinitis. OBJECTIVE: We aimed to determine whether
      class switching to IgE also occurs in the bronchial mucosa in asthma, and to look
      for possible differences/similarities between atopic and nonatopic asthma.
      METHODS: We have used RT-PCR to examine epsilon immunoglobulin heavy-chain
      germline gene transcripts (GLTs; epsilonGLTs), epsilon circle transcripts (CTs;
      Ivarepsilon-Cmu CT or Ivarepsilon-Cgamma CT), and mRNA encoding the heavy chain
      of IgE (epsilon mRNA) and activation-induced cytidine deaminase (AID) in
      bronchial biopsies from atopic patients with asthma, nonatopic patients with
      asthma, atopic controls without asthma, and nonatopic controls without asthma (10
      subjects in each group). RESULTS: The varepsilonGLT and AID mRNA were detectable
      in the bronchial mucosa of subjects in all 4 groups. In contrast, Iepsilon-Cmu
      CT, Ivarepsilon-Cgamma CT, and epsilon mRNA were detectable in the bronchial
      mucosa of the majority of both atopic and nonatopic patients with asthma, but
      rarely in the controls without asthma. CONCLUSION: The bronchial mucosa is a site
      primed in all individuals for class switching to IgE, because of B-cell
      expression of epsilonGLT and AID mRNA. However, it is only in patients with
      asthma, regardless of atopic status, that class switching to IgE occurs. CLINICAL
      IMPLICATIONS: Our findings reveal prospects for local targeting of the Ig class
      switch mechanism in the management of atopic and nonatopic asthma.

PMID- 17208605
TI  - JMF2-1, a lidocaine derivative acting on airways spasm and lung allergic
      inflammation in rats.
AB  - BACKGROUND: Prior reports show that nebulized lidocaine might be an effective
      treatment for asthma. OBJECTIVE: We sought to determine the anti-inflammatory and
      spasmolytic effects of lidocaine and its analogue, JMF2-1, which we have
      synthesized for reduced local anesthetic activity. METHODS: Blockade of Na(+)
      currents was assayed in cultured GH(3) cells by using the patch-clamp technique,
      whereas anesthesia was assessed in a cutaneous pinching test in rats. Lidocaine
      and its analogue were nebulized into sensitized rats for evaluation of their
      effectiveness on airways spasm and inflammation induced by methacholine and
      allergen, respectively. Tissue histamine release and tracheal spasm triggered by
      allergen challenge in the absence and presence of these treatments were also
      examined in vitro. RESULTS: The 50% inhibitory concentration values for blockade
      of Na(+) currents after treatment with JMF2-1 (25.4 mM) was remarkably higher
      than that of lidocaine (0.18 mM), which is consistent with the weak anesthetic
      capacity of this analogue. In contrast, JMF2-1 was more potent than lidocaine in
      inhibiting allergen-induced histamine release and tracheal spasm. In in vivo
      settings methacholine-induced increase in lung resistance (145%) significantly
      reduced to 72% and 47% after lidocaine and JMF2-1 treatment, respectively. Both
      treatments inhibited by about 81% allergen-evoked eosinophil accumulation into
      the lung tissue. CONCLUSION: Replacement of the 2,6-dimethyl radicals by the 2
      trifluormethyl group on the benzene ring of lidocaine significantly reduces
      anesthetic activity, preserving its ability to prevent key aspects of the
      allergic inflammatory response in the lung. CLINICAL IMPLICATIONS: Nebulized JMF2
      1 might be a means of achieving the antiasthmatic effects of lidocaine without
      the anesthetic effects.

PMID- 17208606
TI  - Regulation of allergic airway inflammation by class I-restricted allergen
      presentation and CD8 T-cell infiltration.
AB  - BACKGROUND: CD8 T cells are known to respond to exogenous antigens through cross
      presentation. The importance of the CD8 cell response in the lung after
      inhalation of allergen and its effects on asthmatic inflammation are less clear.
      OBJECTIVE: We sought to determine the dynamics, nature, and immunoregulatory
      activities of the class I CD8 T-cell response to inhaled allergen. METHODS: We
      studied a murine model of respiratory allergen sensitization, adoptive transfer
      of transgenic T cells, and flow cytometric analysis of lung infiltrates. RESULTS:
      Class I-restricted CD8 T cells responded rapidly to inhaled allergen and
      dominated the acute infiltration of T cells into the lung after secondary
      exposure. CD8 cells in the lung expressed a type 1 phenotype and suppressed the
      systemic IgE response to subsequent immunization. Dendritic cells purified from
      conducting airways or lung tissue were highly efficient at cross-presentation of
      antigen into the class I pathway after intranasal challenge. Adoptive transfer of
      transgenic antigen-specific CD8, but not CD4, cells resulted in increased IL-12
      levels and reduced IL-13 and IL-5 levels in bronchoalveolar lavage fluid, coupled
      with substantially reduced airway eosinophilia after repeated allergen
      inhalation, a process mimicked by intranasal administration of IL-12 and
      inhibited by anti-IL-12 antibody. CONCLUSION: The data suggest that CD8 cells
      specific for inhaled allergens are generated in draining lymph nodes but suppress
      allergic airway inflammation through induction of IL-12 in the lung during
      interaction with respiratory dendritic cells. CLINICAL IMPLICATIONS: Novel
      peptide immunotherapeutics targeting the class I-restricted CD8 T-cell response
      to allergen represent a promising strategy for extrinsic asthma.

PMID- 17208607
TI  - beta-Agonist enhances type 2 T-cell survival and accumulation.
AB  - BACKGROUND: Neurohumoral modulation of immune system function is poorly
      understood. beta-Adrenergic receptor ligands (beta-agonists) subserve numerous
      physiologic processes but also function as pathogenic or therapeutic agents in
      numerous diseases with inflammatory components. OBJECTIVES: We sought to
      establish the effects of beta-agonists and prostaglandin E(2) (PGE(2)) on antigen
      dependent and antigen-independent accumulation of IL-13(+) (type 2) and IFN
      gamma(+) (type 1) T cells. We also sought to clarify the mechanisms mediating the
      effects of these G protein-coupled receptor agonists. METHODS: Effects of beta
      agonists or PGE(2) on T-cell subtype accumulation were assessed in peripheral
      blood lymphocytes cultured with alphaCD3/CD28 or IL-2 by using flow cytometry.
      The role of cyclic AMP-dependent protein kinase (PKA) in mediating agonist
      effects was assessed by means of characterization of (1) phosphorylation of an
      intracellular PKA substrate and (2) T cells from patients with lupus possessing a
      natural defect in PKA activation. RESULTS: beta-Agonists, in contrast to PGE(2),
      increased IL-2-induced accumulation of human type 2 T cells, an effect
      attributable to differential activation of PKA affecting regulation of cell
      proliferation and apoptosis. In T cells from patients with lupus exhibiting
      defective PKA activation, both beta-agonists and PGE(2) promoted an increase in
      type 2 T-cell accumulation. CONCLUSION: G(s)-coupled receptors have the capacity
      to elicit prosurvival signaling in type 2 T cells, which, in most instances, is
      obscured by concomitant and antimitogenic PKA activation. CLINICAL IMPLICATIONS:
      beta-Agonists and other G(s)-coupled receptor agonists have the potential to
      regulate T-cell development to affect disease pathogenesis or the efficacy of
      therapies, and variability of effect relates to the ability to stimulate PKA
      activity.

PMID- 17208608
TI  - Effect of peak expiratory flow rate measurement on exhaled nitric oxide levels in
      children with asthma.

PMID- 17208609
TI  - Hyper-IgE syndrome associated with an IL-4-producing gamma/delta(+) T-cell clone.

PMID- 17208610
TI  - Developing measures of symptom perception for children with asthma.

PMID- 17208612
TI  - Control of airway inflammation.

PMID- 17208614
TI  - In response to dosing omalizumab in allergic asthma.

PMID- 17208615
TI  - Nondisclosure of conflicts of interest is perilous to the advancement of science.

PMID- 17208617
TI  - The direct-to-consumer advertising genie.

PMID- 17208618
TI  - Bulgaria and Romania join the European Union.

PMID- 17208619
TI  - Undermining TRIPS: protectionism at its worst.

PMID- 17208620
TI  - Questions about adjuvant trastuzumab still remain.

PMID- 17208621
TI  - Newborn screening for inherited metabolic disease.

PMID- 17208622
TI  - Decrease in frequency of cerebral palsy in preterm infants.

PMID- 17208623
TI  - Early childhood development: the global challenge.

PMID- 17208624
TI  - User fees or equity funds in low-income countries.

PMID- 17208625
TI  - Vote buying in the UN Security Council.

PMID- 17208626
TI  - Doing the undoable: Magpie Trial long-term follow-up.

PMID- 17208627
TI  - Cesar Victora: leader in child health and development.

PMID- 17208628
TI  - Severe acute hepatitis in a patient treated with anastrozole.

PMID- 17208629
TI  - Violence against women and children.

PMID- 17208630
TI  - Violence against women and children.

PMID- 17208631
TI  - Violence against women and children.

PMID- 17208632
TI  - Cholesterol lowering in patients with CHD and metabolic syndrome.

PMID- 17208633
TI  - Cholesterol lowering in patients with CHD and metabolic syndrome.

PMID- 17208635
TI  - Cholesterol lowering in patients with CHD and metabolic syndrome.

PMID- 17208636
TI  - Cholesterol lowering in patients with CHD and metabolic syndrome.

PMID- 17208637
TI  - Japan's aid commitment to health and Africa.

PMID- 17208638
TI  - Public assessment of priorities for research: a citizens' jury.

PMID- 17208639
TI  - 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive
      breast cancer: a randomised controlled trial.
AB  - BACKGROUND: Trastuzumab--a humanised monoclonal antibody against HER2--has been
      shown to improve disease-free survival after chemotherapy in women with HER2
      positive early breast cancer. We investigated the drug's effect on overall
      survival after a median follow-up of 2 years in the Herceptin Adjuvant (HERA)
      study. METHODS: HERA is an international multicentre randomised trial that
      compared 1 or 2 years of trastuzumab treatment with observation alone after
      standard neoadjuvant or adjuvant chemotherapy in women with HER2-positive node
      positive or high-risk node negative breast cancer. 5102 women participated in the
      trial; we analysed data from 1703 women who had been randomised for treatment
      with trastuzumab for 1 year and 1698 women from the control group, with median
      follow-up of 23.5 months (range 0-48 months). The primary endpoint of the trial
      was disease-free survival. Here, we assess overall survival, a secondary
      endpoint. Analyses were done on an intent-to-treat basis. This trial is
      registered with the European Clinical Trials Database, number 2005-002385-11.
      FINDINGS: 97 (5.7%) patients randomised to observation alone and 58 (3.4%)
      patients randomised to 1 year of treatment with trastuzumab were lost to follow
      up. 172 women stopped trastuzumab prematurely. 59 deaths were reported for
      trastuzumab and 90 in the control group. The unadjusted hazard ratio (HR) for the
      risk of death with trastuzumab compared with observation alone was 0.66 (95% CI
      0.47-0.91; p=0.0115). 218 disease-free survival events were reported with
      trastuzumab compared with 321 in the control group. The unadjusted HR for the
      risk of an event with trastuzumab compared with observation alone was 0.64 (0.54
      0.76; p<0.0001). INTERPRETATION: Our results show that 1 year of treatment with
      trastuzumab after adjuvant chemotherapy has a significant overall survival
      benefit after a median follow-up of 2 years. The emergence of this benefit after
      only 2 years reinforces the importance of trastuzumab in the treatment of women
      with HER2-positive early breast cancer.

PMID- 17208640
TI  - Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency
      in Australia: a cohort study.
AB  - BACKGROUND: Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the disorder
      thought most to justify neonatal screening by tandem-mass spectrometry because,
      without screening, there seems to be substantial morbidity and mortality. Our aim
      was to assess the overall effectiveness of neonatal screening for MCAD deficiency
      in Australia. METHODS: We identified MCAD-deficient patients from a total
      population of 2,495,000 Australian neonates (810,000 screened) born between April
      1, 1994, and March 31, 2004. Those from a cohort of 1,995,000 (460,000 screened)
      were followed up for at least 4 years, and we recorded number of deaths and
      severe episodes, medical and neuropsychological outcome, and hospital admissions
      within the screened and unscreened groups. FINDINGS: In cohorts aged at least 4
      years there were 35 MCAD-deficient patients in those not screened (2.28 per
      100,000 total population) and 24 in the screened population (5.2 per 100,000). We
      estimated that patients with this disorder in the unscreened cohort remained
      undiagnosed. Before 4 years of age, three screened patients had an episode of
      severe decompensation (including one neonatal death) versus 23 unscreened
      patients (including five deaths). At the most conservative estimate, relative
      risk of an adverse event was 0.44 (95% CI 0.13-1.45). In the larger cohort the
      relative risk (screened vs unscreened) of an adverse event by age 2 years was
      0.26 (95% CI 0.07-0.97), also a conservative estimate. 38 of 52 living patients
      had neuropsychological testing, with no suggestions of significant differences in
      general cognitive outcome between the groups. INTERPRETATION: Screening is
      effective in patients with MCAD deficiency since early diagnosis reduces deaths
      and severe adverse events in children up to the age of 4 years.

PMID- 17208641
TI  - Trends in cerebral palsy among infants of very low birthweight (<1500 g) or born
      prematurely (<32 weeks) in 16 European centres: a database study.
AB  - BACKGROUND: The risk of cerebral palsy, the commonest physical disability of
      children in western Europe, is higher in infants of very low birthweight (VLBW)-
      those born weighing less than 1500 g--and those from multiple pregnancies than in
      infants of normal birthweight. An increasing proportion of infants from both of
      these groups survive into childhood. This paper describes changes in the
      frequency and distribution of cerebral palsy by sex and neurological subtype in
      infants with a birthweight below 1000 g and 1000-1499 g in the period 1980-96.
      METHODS: A group of 16 European centres, Surveillance of Cerebral Palsy in
      Europe, agreed a standard definition of cerebral palsy and inclusion and
      exclusion criteria. Data for children with cerebral palsy born in the years 1980
      96 were pooled. The data were analysed to describe the distribution and
      prevalence of cerebral palsy in VLBW infants. Prevalence trends were expressed as
      both per 1000 livebirths and per 1000 neonatal survivors. FINDINGS: There were
      1575 VLBW infants born with cerebral palsy; 414 (26%) were of birthweight less
      than 1000 g and 317 (20%) were from multiple pregnancies. 1426 (94%) had spastic
      cerebral palsy, which was unilateral (hemiplegic) in 336 (24%). The birth
      prevalence fell from 60.6 (99%CI 37.8-91.4) per 1000 liveborn VLBW infants in
      1980 to 39.5 (28.6-53.0) per 1000 VLBW infants in 1996. This decline was related
      to a reduction in the frequency of bilateral spastic cerebral palsy among infants
      of birthweight 1000-1499 g. The frequency of cerebral palsy was higher in male
      than female babies in the group of birthweight 1000-1499 g (61.0 [53.8-68..2] vs
      49.5 [42.8-56.2] per 1000 livebirths; p=0.0025) but not in the group of
      birthweight below 1000 g. INTERPRETATION: These data from a large population base
      provide evidence that the prevalence of cerebral palsy in children of birthweight
      less than 1500 g has fallen, which has important implications for parents, health
      services, and society.

PMID- 17208642
TI  - Dental caries.
AB  - Dental caries, otherwise known as tooth decay, is one of the most prevalent
      chronic diseases of people worldwide; individuals are susceptible to this disease
      throughout their lifetime. Dental caries forms through a complex interaction over
      time between acid-producing bacteria and fermentable carbohydrate, and many host
      factors including teeth and saliva. The disease develops in both the crowns and
      roots of teeth, and it can arise in early childhood as an aggressive tooth decay
      that affects the primary teeth of infants and toddlers. Risk for caries includes
      physical, biological, environmental, behavioural, and lifestyle-related factors
      such as high numbers of cariogenic bacteria, inadequate salivary flow,
      insufficient fluoride exposure, poor oral hygiene, inappropriate methods of
      feeding infants, and poverty. The approach to primary prevention should be based
      on common risk factors. Secondary prevention and treatment should focus on
      management of the caries process over time for individual patients, with a
      minimally invasive, tissue-preserving approach.

PMID- 17208643
TI  - Developmental potential in the first 5 years for children in developing
      countries.
AB  - Many children younger than 5 years in developing countries are exposed to
      multiple risks, including poverty, malnutrition, poor health, and unstimulating
      home environments, which detrimentally affect their cognitive, motor, and social
      emotional development. There are few national statistics on the development of
      young children in developing countries. We therefore identified two factors with
      available worldwide data--the prevalence of early childhood stunting and the
      number of people living in absolute poverty--to use as indicators of poor
      development. We show that both indicators are closely associated with poor
      cognitive and educational performance in children and use them to estimate that
      over 200 million children under 5 years are not fulfilling their developmental
      potential. Most of these children live in south Asia and sub-Saharan Africa.
      These disadvantaged children are likely to do poorly in school and subsequently
      have low incomes, high fertility, and provide poor care for their children, thus
      contributing to the intergenerational transmission of poverty.

PMID- 17208644
TI  - Drug treatments for obesity: orlistat, sibutramine, and rimonabant.
AB  - Antiobesity treatment is recommended for selected patients in whom lifestyle
      modification is unsuccessful. Two antiobesity drugs are currently licensed for
      long-term use. Orlistat, a gastrointestinal lipase inhibitor, reduces weight by
      around 3 kg on average and decreases progression to diabetes in high-risk
      patients; adverse gastrointestinal effects are common. Sibutramine, a monoamine
      reuptake inhibitor, results in mean weight losses of 4-5 kg, but is associated
      with increases in blood pressure and pulse rate. Rimonabant, the first of the
      endocannabinoid receptor antagonists, reduces weight by 4-5 kg on average and
      improves waist circumference and concentrations of HDL cholesterol and
      triglyceride; however, an increased incidence of mood-related disorders has been
      reported. To date, all antiobesity drug trials have been limited by their high
      attrition rates and lack of long-term morbidity and mortality data. Other
      promising antiobesity drugs, including those acting within the central
      melanocortin pathway, are in development, but are years away from clinical use.
      In light of the lack of successful weight-loss treatments and the public-health
      implications of the obesity pandemic, the development of safe and effective drugs
      should be a priority. However, as new drugs are developed we suggest that the
      assessment processes should include both surrogate endpoints (ie, weight loss)
      and clinical outcomes (ie, major obesity-related morbidity and mortality). Only
      then can patients and their physicians be confident that the putative benefits of
      such drugs outweigh their risks and costs.

PMID- 17208645
TI  - Lethal ECG changes hidden by therapeutic hypothermia.

PMID- 17208647
TI  - Contrast echocardiography.
AB  - Myocardial contrast echocardiography (MCE) is a noninvasive imaging technique
      that relies on the ultrasound detection of microbubble contrast agents. These
      agents are confined to the intravascular space thereby producing signal
      enhancement from the blood pool. This review encompasses many of the key concepts
      regarding the clinical application of MCE. The first section focuses on the
      composition, safety, and biokinetics of ultrasound contrast agents. Then we
      discuss new ultrasound imaging methodology that has been developed to enhance
      detection of contrast agent and to assess perfusion at the tissue level. Next,
      the clinical applications of contrast ultrasound are reviewed. These include
      enhancement of the cardiac chambers for better assessment of cardiac function and
      masses, myocardial perfusion imaging for the detection of coronary artery
      disease, and the assessment of myocardial viability and microvascular reflow.
      Finally, we discuss some of the future applications for MCE, which include
      molecular imaging of disease and drug/gene delivery. The overall aim of the
      review is to update the clinician on state-of-the-art MCE and how it can be
      applied in patients with cardiovascular disease.

PMID- 17208648
TI  - Soul, mind, brain: Greek philosophy and the birth of neuroscience.
AB  - The nature of "soul" and the source of "psychic life", the anatomical seat of
      cognitive, motor and sensory functions, and the origin of neural diseases were
      broadly debated by ancient Greek scientists since the earliest times. Within the
      space of few centuries, speculation of philosophers and medical thinkers laid the
      foundations of modern experimental and clinical neuroscience. This review
      provides a brief history of the leading doctrines on the essence of soul and the
      properties of mind professed by Greek philosophers and physicians as well as the
      early attempts to localize brain faculties and to explain neural disorders.

PMID- 17208649
TI  - Projections of primary afferent fibers to last-order premotor interneurons in the
      lumbar spinal cord of rats.
AB  - It is well established that last-order premotor interneurons in the spinal cord
      have crucial importance in the integration of activities generated by the spinal
      motor apparatus, sensory information and volleys arising from higher motor
      centers, indicating that they play a substantial role in spinal motor functions.
      Despite extensive studies, synaptic input systems of these neurons have not been
      investigated in detail up to now with morphological approaches. On this basis,
      the present experiments were aimed at the visualization of possible contacts
      between primary afferents and last-order premotor interneurons in the lumbar
      spinal cord of rats using double label neural tracing methods in light
      microscopy. The findings show that terminal puncta of primary afferents do
      establish indeed appositions on last-order premotor interneurons. From the
      quantitative point of view, these appositions occur, however, in limited numbers.
      The study also shows that last-order premotor interneurons contacted by primary
      afferents tend to be concentrated at the segmental level of the innervated
      motoneurons, and are evenly distributed along the mediolateral extent of laminae
      V-VI and in the dorsal portion of lamina VII.

PMID- 17208650
TI  - Net without nodes and vice versa, the paradoxical Golgi-Cajal story: a
      reconciliation?
AB  - In 1906, the first Nobel prize in the neurosciences was awarded jointly to
      Camillo Golgi and Santiago Ramon y Cajal in recognition of their work on the
      structure of the nervous system. The Nobel Prize in Physiology or Medicine linked
      together forever these two scientists. One century later, what remains of their
      opposite views on the brain?

PMID- 17208651
TI  - Circadian and ultradian influences on dreaming: a dual rhythm model.
AB  - The dual rhythm model of dreaming states that, under high sensory thresholds,
      heightened general cortical activation common to both REM/NREM and circadian
      driven activation cycles sums to produce the main characteristics of dreaming. In
      addition, the unique pattern of regional brain activation characteristic of REM
      sleep amplifies the emotional intensity of the dream. Subjects were awakened from
      REM and NREM sleep once near the nadir of the core body temperature rhythm, where
      circadian-driven cortical activation was assumed to be low, and again in the late
      morning, where this activation was presumed to be high. As predicted, changes in
      the central characteristics of dream reports mirrored REM/NREM and circadian
      driven fluctuations in general activation, while at the same time, the regional
      activation pattern unique to REM sleep amplified dream emotionality selectively
      in REM reports.

PMID- 17208652
TI  - A map of the major nuclei of the fetal sheep brainstem.
AB  - The fetal sheep has been used to investigate a wide range of developmental and
      pathological processes such as the effect of severe hypoxia, asphyxia, or
      intrauterine infection on the brain but, until now, there has been no complete
      description of the normal anatomical organisation of neuronal groups to
      facilitate interpretation of these studies. In this paper, we describe the major
      nuclei of the fetal sheep brainstem based on a study of 5 fetal sheep at 140 days
      of gestation (G140: term is G147). Nuclei were identified with the aid of brain
      atlases available for other species, and from the previously published, partial
      descriptions available for the sheep. Fifty-five distinct nuclei were identified
      after Nissl (thionin) staining, and their caudal and rostral margins were
      defined. This paper provides an easy reference to the position of the major
      nuclei within the fetal sheep brainstem, and can be used as a guide for future
      studies examining the organisation of neuronal populations under normal and
      pathological conditions in this animal model.

PMID- 17208653
TI  - Prefrontal dopamine efflux during exposure to drug-associated contextual cues in
      rats with prior repeated methamphetamine.
AB  - Conditioned stimulus-reward response and prefrontal dopamine efflux under context
      previously paired with methamphetamine administration were assessed in rats with
      or without prior sensitizing regimen. Sensitizing pretreatment was administered
      with methamphetamine (1mg/kg, every other day for six sessions) for behavioral
      sensitization. The animals received methamphetamine (1mg/kg) or saline injection
      (each for six sessions) to pair with distinct contexts on alternate days to
      induce conditioned place preference. Then, dopamine outflows in the medial
      prefrontal cortex were analyzed on the next day via microdialysis study as
      animals exposed to the methamphetamine or saline-paired context, respectively.
      Prefrontal DA efflux increased in those rats without sensitizing pretreatment,
      while they occupied the methamphetamine-paired chamber. The rats with prior
      sensitizing regimen demonstrated more robust conditioned place preference than
      those without pretreatment, however, their dopamine efflux was attenuated, while
      remaining in methamphetamine-paired context. It is suggested that the attenuated
      responsiveness of mesocortical dopamine transmission in prior sensitized rats
      may, at least in part, be responsible for their augmented conditioned place
      preference, which resulted from activation of related brain areas that together
      strengthen the associative learning to drug-related stimuli. This paradigm may
      reflect a dysregulated prefrontal function in the methamphetamine abusers.

PMID- 17208654
TI  - Antioxidant response and oxidative damage in brain cortex after high dose of
      pilocarpine.
AB  - Pilocarpine is a cholinergic agonist capable to induce seizures and an
      epilepticus-like state in rodents. This status epilepticus (SE) is an useful
      animal model to study the development and understanding of the neuropathology,
      behavioural and electroencephalographic alterations of human temporal lobe
      epilepsy. It has been suggested a relationship between SE and reactive oxygen
      species (ROS) that can result in seizure-induced neurodegeneration. The aim of
      this study was to evaluate the existence of oxidative damage and the changes in
      the antioxidant system in cortex after administration of a high pilocarpine dose.
      Rats were injected with pilocarpine (350 mg/kg i.p.) or with saline as control
      and 2h after the animals were sacrificed. Malondialdehyde (MDA) levels, as marker
      of lipid peroxidation, significantly increased (64%) after pilocarpine treatment
      evidencing oxidative damage. Antioxidant enzyme activities--catalase (CAT),
      glutathione peroxidase (GP) and superoxide dismutase (SOD)--significantly
      increased in response to pilocarpine (28%, 28% and 21%, respectively). GP and Mn
      SOD gene expression were induced by pilocarpine treatment. Vitamin E
      concentration in brain cortex decreased (15%) as result of pilocarpine
      administration. In conclusion, the high dose of pilocarpine, used in the present
      study, induces oxidative damage and increases antioxidant enzyme activities and
      expression in brain cortex. Moreover, increased lipid peroxidation produces the
      consumption of Vitamin E.

PMID- 17208655
TI  - Mechanisms underlying the long-term behavioral effects of traumatic experience in
      rats: the role of serotonin/noradrenaline balance and NMDA receptors.
AB  - Traumatic stressors induce long-lasting changes in behavior. It is believed that
      all three glutamatergic, serotonergic and noradrenergic neurotransmission play a
      role in the development of such behavioral changes, but their relative importance
      and relationship is poorly understood. We have shown previously that a single
      exposure of rats to electric shocks induces social avoidance for about 10 days.
      Here we assessed social avoidance 24 h after shock exposure in rats with
      chemically lesioned serotonergic and noradrenergic neurons. The effects of the
      NMDA receptor blocker MK-801 were also studied. When the serotonin/noradrenaline
      balance was shifted towards serotonergic dominance via chemical lesions, the
      behavioral dysfunction was markedly attenuated. The disruption of serotonergic
      neurotransmission (that lead to noradrenergic dominance) significantly increased
      the behavioral deficit. Shock responding was not secondary to lesion-induced
      differences in social behavior. Noteworthy, the brain noradrenaline/serotonin
      ratio correlated negatively with shock-induced social avoidance, suggesting that
      the ratio rather than absolute levels are important in this respect. In line with
      this assumption, double lesions had minor effects on social avoidance, suggesting
      that these monoaminergic systems modulate, but do not mediate the behavioral
      deficit. The blockade of NMDA receptors abolished the development of stress
      induced social avoidance both when applied before shocks and when applied before
      behavioral testing. We confirmed that the long-term behavioral effects of
      traumatic experience result from glutamatergic activation, the effects of which
      are mediated by NMDA receptors. The development of the behavioral deficit is
      modulated by the balance between serotonergic and noradrenergic
      neurotransmission, possibly via effects on shock-induced glutamatergic
      activation.

PMID- 17208656
TI  - Neuromedin C microinjected into the amygdala inhibits feeding.
AB  - Bombesin-like peptides including gastrin releasing peptide and neuromedin C are
      known to inhibit feeding. Bombesin receptors have been found in moderate to high
      densities in the amygdaloid body, which is essentially involved in the regulation
      of feeding and body weight. In the present experiments neuromedin C (15, 30, and
      60 ng), a carboxyterminal decapeptid fragment of gastrin releasing peptide, was
      bilaterally microinjected into the central part of the amygdala in ad libitum fed
      male CFY rats. Food intake was measured every 5 min for 30 min and also 6 min
      following neuromedin C or vehicle microinjections. Fifteen nanograms neuromedin C
      significantly suppressed liquid food consumption for 5 min and 30 ng for 25 min.
      However, 60 ng was not effective. Neuromedin C effects were blocked by prior
      application of the bombesin receptor antagonist [Leu(13)-psi(CH(2)NH)-Leu(14)]
      bombesin. Neuromedin C treatment increased latency to feeding, decreased food
      intake, decreased the time spent feeding and their ratio, the number and the
      duration of feeding episodes during the first 5 min, without modifying body
      temperature or stereotype activity. Results indicate that neuromedin C may
      decrease the efficiency of feeding and that activation of bombesin receptors in
      the central amygdala may reduce appetite.

PMID- 17208657
TI  - Cocaine exposure during adolescence affects anxiety in adult mice.
AB  - Psychostimulant drugs such as cocaine have profound and long-lasting
      neurobiological effects, which may affect anxiety or social behaviors. These
      actions could be greater when cocaine is administered during a developmental
      period such as adolescence. The present work attempts to further clarify the long
      lasting effects of cocaine administration on mice, examining three major
      variables: age; pattern of drug administration; and housing conditions.
      Adolescent (postnatal day 26) or early adult mice (postnatal day 46) were exposed
      to a daily or binge cocaine administration and 15 days later their behavior was
      evaluated, the mice being housed either in isolation or in groups during this
      stage. After a period free of drug, the behaviors evaluated were: spontaneous and
      cocaine-induced motor activity; anxiety, using the elevated plus maze; the social
      profile, assessed in a social interaction test. Daily cocaine administration
      increased avoidance and flee in isolated adolescent-treated mice and decreased
      social contacts in those which were grouped. On the other hand, the binge pattern
      modified the anxiety of the grouped adolescent-treated mice evidenced by the
      increase in time spent on the open arms of the plus maze. An increase in
      spontaneous and cocaine-induced motor activity was shown in animals after a daily
      pre-treatment. The results are discussed in terms of presenting cocaine-induced
      behavioral changes within a specific temporal window and depending on the three
      variables studied.

PMID- 17208658
TI  - Somatosensory-evoked potentials indicate increased unpleasantness of noxious
      stimuli in response to increasing stimulus intensities in the rat.
AB  - Recently, it has been shown in rats that specific characteristics of
      somatosensory-evoked potentials (SEPs) recorded from different sites on the scalp
      correlate differently to the amount of unpleasantness experienced by the animal
      following noxious stimulation. It was shown that the SEP recorded from vertex (Vx
      SEP) did correlate with the unpleasantness, whereas the SEP recorded from the
      primary somatosensory cortex (SI-SEP) did not. In the present study, we further
      investigated the relationship between the Vx-SEP, SI-SEP and the unpleasantness
      of noxious stimuli. Therefore, different groups of rats were subjected to a SEP
      fear-conditioning paradigm in which the unconditioned stimulus (US), represented
      by noxious stimuli applied to evoke SEPs, was paired to a conditioned stimulus
      (CS) represented by a tone. Different stimulus intensities of the US were applied
      in the different groups. After CS-US presentation, CS-induced fear-conditioned
      behaviour was analysed in relation to the characteristics of the Vx- and SI-SEP
      during CS-US presentation. Results showed that increasing stimulus intensities
      led to increased SEP amplitudes, which were paralleled by an increased amount of
      CS-induced fear-conditioned behaviour. No differences between Vx-SEP and SI-SEP
      were found. The increase in the SEPs in parallel with the increased amount of
      fear-induced behaviour further supports the SEP to be a potentially valuable tool
      for studying acute pain and analgesia in animals.

PMID- 17208659
TI  - Natriuretic peptide receptor-A is functionally expressed on bullfrog retinal
      Muller cells.
AB  - By the patch clamp technique, whole-cell currents induced by brain natriuretic
      peptide (BNP) from isolated bullfrog retinal Muller cells were studied.
      Application of 100 nM BNP induced a sustained inward current from these cells
      with a reversal potential of about 0 mV, and the current could be completely
      blocked by anantin, an antagonist of the A-type NP receptor (NPR-A) and CdCl(2),
      a blocker of cyclic nucleotide-gated (CNG) non-selective cation channels.
      Likewise, perfusion with the membrane-permeable cGMP analog 8-bromoguanosine
      3',5'-cyclic monophosphate (8Br-cGMP) caused effects that are similar to those of
      BNP. Moreover, application of BNP failed to induce any current in the presence of
      1 mM 8Br-cGMP. By calcium imaging, we further showed a significant increase in
      intracellular calcium levels ([Ca(2+)](i)) of all parts of Muller cells,
      including the endfoot, soma and processes following the perfusion of BNP, and the
      increase could be blocked by anantin. All these results suggest that NPR-A is
      expressed in bullfrog Muller cells, and activation of the receptor causes an
      increase of intracellular cGMP levels that activates CNG channels and thereby
      results in an increased calcium influx.

PMID- 17208660
TI  - Short-term synaptic plasticity in layer II/III of the rat anterior cingulate
      cortex.
AB  - Recent in vivo electrophysiological studies in our laboratory demonstrated medial
      thalamus (MT) induced short-term facilitation in the middle layers of the
      anterior cingulate cortex (ACC). The aim of the present study was to investigate
      different forms of short-term plasticity (STP) in layer II/III of the ACC in an
      in vitro slice preparation. Extracellular field potentials in layer II/III
      consisting of an early component (fAP) and a late component (fPSP) were activated
      by electrical stimulation of the deep layers. The fPSP and intracellularly
      recorded excitatory post-synaptic potential (EPSP) could be facilitated by paired
      pulse stimulation at a low frequency (0.033Hz, pulse interval 20-400ms). An
      initial facilitation and subsequent depression were obtained when high frequency
      (12.5, 25 and 50Hz) tetanus stimulations were applied to the ACC slice. A post
      tetanic augmentation 30s in duration was also observed. The effects of tetanic
      stimulation were altered in the presence of an increased or a decreased calcium
      concentration. Application of omega-conotoxin GVIA (CTX) in normal calcium
      concentration conditions decreased overall responses during tetanic stimulation
      similar to reducing calcium exposure. However CTX application did not increase
      paired-pulse facilitation (PPF) as is seen under low calcium conditions. These
      results indicate that calcium is involved in the formation of certain features of
      STP in layer II/III of the ACC and that N-type calcium channels contribute to
      some, but not all, components of these plastic changes. Two-site electrical
      stimulation testing showed that two separate presynaptic inputs can produce short
      term facilitation. Our findings implicate a post-synaptic mechanism in STP in
      layer II/III of the ACC.

PMID- 17208661
TI  - The effect of response type (motor output versus mental counting) on the
      intracerebral distribution of the slow cortical potentials in an externally cued
      (CNV) paradigm.
AB  - OBJECTIVE: Previous surface CNV studies including a hand motor output have
      suggested that the late phase of the CNV reflects the preparation of the
      sensorimotor cortices involved in the motor output given the same similarity in
      scalp potential distribution with readiness potential. However, the poor spatial
      resolution of the scalp recorded CNV data prevented a definitive conclusion. This
      intracerebral study allowed us to test this hypothesis using a CNV paradigm in
      which a non-motor task is used as a reference. This study concerned the
      intracerebrally located generators of the Contingent Negative Variation in two
      different paradigm settings: (i) motor output required, (ii) silent counting
      required (non-motor control condition). METHODS: Stereoelectroencephalography
      (SEEG) recordings of the contingent negative variation (CNV) in a somato
      somatosensory stimulation paradigm with a motor or counting task were taken from
      nine patients with drug-resistant epilepsy. The intracerebral recordings were
      taken from 25 cortical areas in both hemispheres (supplementary motor area-SMA;
      the cingulate gyrus; the orbitofrontal, premotor and dorsolateral prefrontal
      cortices; lateral temporal cortex, amygdalohippocampal complex; and the
      parietooccipital cortex). RESULTS: The slow waves were generated in the SMA, the
      premotor, dorsolateral, and orbitofrontal cortices, the cingulate gyrus, and
      parts of the lateral temporal, mesial temporal structures and parietal cortex. We
      found a significant difference between the two tasks in the CNV potential
      generation. The task with the motor output produced significantly higher numbers
      of CNV potential generators when compared to the task with silent counting.
      CONCLUSIONS: The CNV potential generators varied between motor and non-motor
      tasks. The intracerebral distribution of the potentials linked with expectation
      is task dependent. Our main conclusion is that the executive network is more
      active during the motor task than during counting task.

PMID- 17208662
TI  - The relation of adipose tissue to cardiometabolic risk.
AB  - Adipose tissue is an active and complex endocrine organ that secretes numerous
      bioactive substances, including hormones, growth factors, and cytokines. Central
      obesity, one of the components of metabolic syndrome, is a cardiometabolic risk
      factor associated with a state of chronic inflammation and coagulation, one in
      which the expression of certain adipocytokines, including tumor necrosis factor
      alpha (TNF-(alpha), interleukin (IL)-6, and plasminogen activator inhibitor-1
      (PAI-1) is more abundantly increased, while adiponectin expression is decreased.
      TNF-alpha initiates and organizes inflammatory changes in vascular tissue. IL-6,
      an inflammatory cytokine directly implicated in atherogenesis, exerts pleiotropic
      effects on a variety of tissues. An increased concentration of PAI-1, an
      important regulator of the endogenous fibrinolytic system, promotes continued
      clotting. Adiponectin, on the other hand, has potent vasculoprotective,
      angiogenic, anti-inflammatory, and antiatherogenic properties. Adiponectin levels
      are low in obese individuals and increase when weight is lost, thereby serving as
      a marker for cardioprotection. Weight loss has long been promoted as a means to
      reduce the risk of type 2 diabetes and cardiovascular disease; for example,
      exercise and a hypocaloric diet have been shown to decrease PAI-1 levels. Weight
      loss drugs, such as orlistat, a lipase inhibitor, and sibutramine, a serotonin
      and norepinephrine reuptake inhibitor, have both been shown to produce a decrease
      in C-reactive protein levels and an increase in serum adiponectin. Rimonabant, a
      selective cannabinoid 1 receptor antagonist in Phase III studies, also has been
      shown to increase adiponectin levels. These agents may play a role in the
      regulation of adipocytokines, which may directly affect the risk for
      cardiometabolic disease.

PMID- 17208664
TI  - The endocannabinoid system: body weight and metabolic regulation.
AB  - The endocannabinoid system elicits multiple physiologic functions that are not
      fully understood. Antagonism of cannabinoid type 1 (CB(1)) receptors has been the
      only successful new pharmacologic treatment approach in Phase III studies in
      obesity in the last 8 years. Whereas antagonism of (CB(1)) receptors acutely
      reduces food intake, the long-term effects on weight reduction and metabolic
      regulation appear to be mediated by stimulation of energy expenditure and by
      peripheral effects related to liver, skeletal muscle, adipose tissue, and
      pancreas physiology. For example, in the liver, lipogenic enzymes and fatty acid
      synthesis are upregulated by endocannabinoids, and in adipose tissue, antagonism
      of (CB(1)) receptors increases secretion of adiponectin. Some studies suggest
      that endocannabinoid formation is increased in obesity, perhaps because
      endocannabinoid degradation is decreased. Although many questions remain
      unanswered at present, the emerging concept of endocannabinoids as metabolic
      regulators helps to explain the success of rimonabant (SR141716), an antagonist
      of (CB(1)) receptors, currently in Phase III studies.

PMID- 17208666
TI  - Adipose tissue dysfunction in obesity and lipodystrophy.
AB  - The primary function of adipose tissue is to store energy in the form of
      triglycerides during periods of energy excess and to release the energy during
      fasting or starvation as free fatty acids and glycerol. Adipose tissue secretes a
      variety of peptides called adipocytokines (eg, leptin, adiponectin, tumor
      necrosis factor-alpha, interleukin-6, resistin, visfatin) that have endocrine,
      autocrine, and paracrine effects on the brain, liver, and skeletal muscles. These
      peptides play an important role in the regulation of energy homeostasis and
      intermediary metabolism. Adipose tissue also aromatizes androgens to estrogens,
      and some adipose tissue depots (mechanical fat) serve a protective or cushioning
      function. Dysfunction of adipose tissue can result in insulin resistance and its
      metabolic complications in patients with excess body fat (obesity) or markedly
      reduced body fat (lipodystrophy). Alterations in free fatty acid and
      adipocytokine release from adipose tissue may underlie metabolic complications.

PMID- 17208667
TI  - No child left behind...visually.

PMID- 17208668
TI  - Paraoptometry as a career.

PMID- 17208669
TI  - Optic disc drusen: complications and management.
AB  - BACKGROUND: Disc drusen have been found clinically in 0.3% of the population with
      up to 91% presenting bilaterally. Disc drusen gradually change in their
      ophthalmoscopic appearance throughout a patient's lifespan. This case highlights
      the possible ocular complications of disc drusen and the complexity in their
      treatment because of the risk of visual acuity loss. CASE REPORT: A 43-year-old
      patient with documented bilateral buried disc drusen presented without symptoms
      for a routine examination. A subretinal neovascular membrane (SNVM) one quarter
      of a disc diameter in size with an adjacent subretinal hemorrhage was observed in
      the right eye with a small subretinal hemorrhage in the fellow eye. The patient
      was evaluated by a retinologist who deferred photocoagulation of the SNVM
      considering its nasal disc location. CONCLUSIONS: Diagnosing disc drusen is
      critical because of the serious pathology they can mimic, including disc edema.
      Although typically benign, patients with disc drusen should be monitored on a
      regular basis to rule out ocular complications, which can be potentially sight
      threatening.

PMID- 17208670
TI  - The use of tinted contact lenses in the management of achromatopsia.
AB  - BACKGROUND: Achromatopsia is a congenital, autosomal recessively inherited
      condition in which cones are either defective or absent. Complete achromatopsia
      results from having only rods as functioning photoreceptors. Many people with
      achromatopsia have small amounts of residual cone function that may provide
      minimal color vision under special circumstances. Clinical findings associated
      with the condition include reduced visual acuity, nystagmus, a greater than
      normal incidence of high ametropia, and severe photophobia. The photophobia
      resulting from achromatopsia can be debilitating even in normal indoor
      illumination. Tinted contact lenses have been reported to reduce photophobia and
      improve visual function in these patients. CASES: Two cases are reported here. A
      32-year-old man presented with reduced and stable visual acuity, complete color
      blindness, nystagmus, and debilitating photophobia. The second patient was a 23
      year-old woman who presented with reduced and stable visual acuity, severely
      impaired color vision, rotary nystagmus, and significant photophobia. Both of
      these patients were fit with centrally tinted contact lenses. Although visual
      acuity did not improve measurably in either patient with tinted compared with
      clear lenses, both experienced a dramatic reduction in photophobia with the
      lenses. CONCLUSION: Tinted spectacle or contact lenses may be useful in relieving
      photophobia associated with a number of cone disorders, including achromatopsia.
      In addition to decreasing light sensitivity, tinted lenses have been reported to
      improve visual acuity, decrease the size of central scotomata, enlarge peripheral
      visual field, and enhance visibility of long wavelength stimuli in bright
      illumination.

PMID- 17208671
TI  - Clinical discussion on the relative efficacy of 2 surfactant-containing
      lubricating agents in removing proteins during contact lens wear.
AB  - BACKGROUND: This clinical study aims to evaluate the clinical efficacy of 2
      popular rewetting agents, Blink-N-Clean, manufactured by Advanced Medical Optics
      (Santa Ana, California), and Clens 100, manufactured by Alcon (Ft. Worth, Texas),
      on protein removal in a nonsymptomatic population of contact lens wearers fitted
      with etafilcon A soft contact lenses, Acuvue 2, manufactured by Vistakon, a
      division of Johnson and Johnson Vision Care (Jacksonville, Florida). METHODS:
      This randomized, double-blind, crossover study was performed on 22 subjects who
      had been fitted successfully with etafilcon A soft contact lenses. Each subject
      was examined on 3 occasions, at 2-week intervals, to evaluate a number of
      clinical signs related to contact lens wear, with or without the use of ocular
      lubricants specifically designed to reduce the levels of proteins adsorbed on the
      lens. A washout period was observed between each of the study's different phases.
      High- and low-contrast visual acuity levels were measured using the Bailey-Lovie
      (logMAR) chart under mesopic and scotopic conditions. Protein levels adsorbed on
      the lenses were determined using a modified Lowry method. Ocular health was
      assessed under biomicroscopy using conventional techniques. Subjective comfort
      was also evaluated, using a questionnaire based on a Likert scale graded from 0
      to 50. RESULTS: Objectively, no significant difference in either visual acuity or
      comfort was found between the use or the nonuse of drops or the use of one
      specific product. Using Clens 100 allowed for a significant reduction in the
      quantity of protein on the lens surface. More than 3 subjects of 4 (77%)
      preferred the Clens 100 product, in large part because they found the size of
      drops dispensed from the Clens 100 bottle less disturbing during insertion
      because of the size of the drops and blur. CONCLUSION: Among healthy contact lens
      wearers fitted with the same type of contact lens, a significant difference was
      observed in the quantity of proteins adsorbed on the lens with the use of Clens
      100, as compared with the use of either Blink-N-Clean or no product at all. This
      difference does not seem to have had an impact because clinical signs and
      symptoms did not vary over the course of the study.

PMID- 17208672
TI  - Evaluation of the Xal-Ease latanoprost delivery system.
AB  - PURPOSE: The purpose of this study was to compare drops of latanoprost dispensed
      using the Xal-Ease (Pfizer Ophthalmics, New York, New York) delivery system with
      drops dispensed manually. METHODS: Twenty-four 2.5-mL bottles of Xalatan (Pfizer
      Ophthalmics) were evaluated with or without the delivery system. Individually
      dispensed drops were counted. The total volume dispensed was measured to the
      nearest 10 microL. Statistical analysis compared group means by analysis of
      variance. P values less than 0.05 were considered significant. RESULTS: The
      overall mean volume was 2,850 microL. Overall mean drops per bottle (n = 24) were
      90.3 +/- 6.3. Using the Xal-Ease, mean drops per bottle were 93.0 +/- 3.4 and
      without it, 87.7 +/- 7.5 (n = 12 each). CONCLUSIONS: With Xal-Ease, mean drops
      per bottle (5) were statistically significantly greater when compared with
      standard dispensing (P = 0.0393). This result is accounted for by more consistent
      individual drop volume and greater volume using the delivery system.

PMID- 17208673
TI  - MRI features of intrahepatic extramedullary haematopoiesis in sickle cell
      anaemia.
AB  - Extramedullary haematopoiesis (EMH) is a reactive mechanism by which blood cells
      are produced outside of the bone marrow to supplement insufficient production or
      increased destruction of erythrocytes. EMH is uncommon in sickle cell anaemia
      (SCA). We report the first case of focal intra-hepatic EMH in SCA depicted on MRI
      occurring in a 32-year-old woman with homozygote SCA and in view of previously
      published data, highlight the diagnostic features suggesting a differential
      diagnosis with other focal liver lesions including infectious, inflammatory or
      primary liver tumors.

PMID- 17208674
TI  - Imaging of tongue carcinoma.
AB  - The tongue enables taste and plays a critical role in formation of food bolus and
      deglutition. The tongue is also crucial for speech and the earliest sign of
      tongue paresis is a change in the quality of speech. Given the importance of the
      tongue, tongue carcinoma should be accurately staged in order to optimise
      treatment options and preserve organ function. The intent of this review is to
      familiarize radiologists with the pertinent anatomy of the tongue and the
      behaviour of tongue carcinoma so as to map malignant infiltration accurately.

PMID- 17208675
TI  - Improving the interpretation of bone marrow imaging in cancer patients.
AB  - Magnetic resonance imaging (MRI) is the best technique for bone marrow imaging.
      The MRI signal of bone marrow depends on the quantity of fat it contains and on
      its cellularity. Evaluation of marrow of patients treated for cancer is
      complicated by age and osseous site related changes in the distribution of normal
      haematopoietic (red) and fatty (yellow) marrow and by the changes induced by
      treatments: decrease in pathological cellularity, increase in fat proportion,
      conversion of red marrow to fatty marrow or, conversely, reconversion of fatty
      marrow in normal haematopoietic red marrow. The treatments used in oncology
      modify pathological marrow but also normal marrow and may sometimes lead to
      complications. These modifications may be focal or diffuse, homogeneous or patchy
      and symmetrical or asymmetric. The knowledge of bone marrow physiological status
      and post-therapeutic patterns is important for the interpretation of marrow
      disorders and effects of therapy and to avoid false-positive diagnosis of marrow
      metastases and tumour progression. The aim of this paper is to recall the MRI
      patterns of normal bone marrow and normal variations and to show the effects of
      treatments on bone tissue and normal bone marrow and treatment-related
      modifications on pathological marrow.

PMID- 17208676
TI  - MRI of the pancreas: tumours and tumour-simulating processes.
AB  - The most important issues in pancreatic imaging are the detection and staging of
      pancreatic cancer, differentiation between cancer and focal pancreatitis, the
      characterization of cystic lesions and the search for neuroendocrine tumours.
      Magnetic resonance (MR) units (1.5 T) with strong gradients and a phased-array
      torso coil should be used, making breath-hold imaging possible in order to avoid
      motion artifacts. Standard imaging sequences are T1-weighted (T1w) gradient
      recalled-echo (GRE) with and without fat saturation. For T2-weighted (T2w)
      imaging, axial single-shot turbo spin-echo (TSE) and coronal/oblique MR cholangio
      pancreatography (MRCP) pulse sequences are preferable. As contrast agents either
      gadolinium agents or mangafodipir trisodium are used. Dynamic gadolinium-enhanced
      T1w fatsat 3D GRE images are helpful to delineate vessel infiltration by
      adenocarcinoma and to assess the aetiology of cystic masses. Mangafodipir
      enhanced MRI has been found to be superior to helical computed tomography (CT) in
      the detection of small cancers and in the delineation of liver metastases. In
      cases of an equivocal pancreatic mass the presence of the "duct penetrating sign"
      at MRCP (i.e., the duct traversing the mass) is suggestive of an inflammatory
      pseudotumour. Hypoattenuation due to focal fatty infiltration may mimic a tumour
      at CT, but in-phase and opposedphased T1w imaging readily depicts the fat. Multi
      detector CT has gained increasing popularity for pancreatic imaging because of
      the 3D visualization of the peripancreatic vessels. However, MR imaging is
      excellent in the delineation of small pancreatic tumours. Due to its superior
      soft tissue contrast, MR imaging is also the method of choice in the differential
      diagnosis between tumours and tumour-simulating conditions in patients with
      equivocal CT and to assess cystic lesions.

PMID- 17208677
TI  - Imaging of metastatic melanoma.
AB  - Cutaneous cancer is now the most common human malignancy and in the UK malignant
      melanoma comprises 11% of all skin cancers. Eighty percent of malignant melanoma
      is thought to be related to excessive exposure to sunlight, particularly in
      childhood. Although the least common skin cancer, malignant melanoma is the most
      deadly. In 1999 it killed over 1600 individuals in the UK and by 2004, in the
      USA, 55,100 new cases were anticipated. The incidence of this disease is
      increasing more rapidly than any other malignancy and in males there was a four
      fold increase in incidence between 1971 and 1997 whilst there was a three-fold
      increase in women. Cutaneous melanoma is arguably the most widely metastasising
      neoplastic disease and it has a particularly unpredictable pattern of spread.
      Imaging has an important role in the management of this disease as the
      demonstration and delineation of metastases influences management and prognosis.

PMID- 17208678
TI  - Diagnosis and staging of small bowel tumours.
AB  - Small bowel neoplasms comprise only 1% of gastrointestinal neoplasms. Despite
      their rarity, it is important to diagnose small bowel tumours early to maximize
      patient survival.

PMID- 17208679
TI  - Upper gastrointestinal tumours: diagnosis and staging.
AB  - Upper GI tumours have a dismal prognosis. Only early diagnosis and accurate
      staging can optimize patient management.

PMID- 17208681
TI  - Agricultural science and food policy for consumers and workers: recipes for
      public health successes or disasters?
AB  - In the world of high speed globalization, the search for global food and water
      security has failed despite being driven by aggressive agribusiness and aided all
      too often by so-called Green Revolution research scientists and technologists. In
      the process, agricultural workers, rural communities, and food production workers
      face significant occupational and environmental hazards. Countervailing forces to
      the World Trade Organization (WTO) and agribusiness food strategies are needed.
      Critical to these forces will be Non-Governmental Organizations (NGOs) working
      toward non-toxic, nondestructive, community-based agriculture informed by
      integrated humanistic, scientifically cautious, worker-sensitive, and
      ecologically located principles.

PMID- 17208682
TI  - A chicken in every pot: at what price?
AB  - The poultry industry is one of the fastest growing industries in the United
      States. "Big chicken," however, has created big problems. Consumers and the
      environment, as well as people who grow, catch, slaughter, and process chicken
      are all impacted by the practices and policies of the poultry industry. This
      paper sheds some light on serious problems caused by production practices that
      put profits above human dignity, food safety, and the environment and proposes
      some needed regulations and actions.

PMID- 17208683
TI  - People, pesticides, and the environment: who bears the brunt of backward policy
      in South Africa?
AB  - Whereas international trends show that many developed countries are adopting
      policies that promote pesticide reduction, use of pesticides in South Africa
      continues to expand. In particular, macroeconomic policies encourage pesticides
      use among emergent small-scale black farmers, while potential exposures of
      workers on commercial farms remain high. Despite having legal controls that seem
      to conform to international standards, the present health and environmental
      impacts of pesticide use in South Africa are substantial and generally
      underestimated. The reasons lie in the fragmentation of regulatory mechanisms as
      well as the absence of public awareness and participation in policy-making
      related to pesticides. Failure to enforce existing legislation, an ambivalent
      relationship between government and industry, and the existence of a "pesticide
      culture" will continue to prevent implementation of meaningful control measures.
      As a result, it is marginalized groups, such as small-scale farmers and farm
      workers, who bear the brunt of policies that have not kept pace with a growing
      international awareness of the hazards of widespread pesticide use for human
      health and for the environment. Opportunities for fundamental transformation of
      the legal and policy framework relating to pesticides in order to promote
      environmental justice are explored.

PMID- 17208684
TI  - Occupational health and safety of workers in agriculture and horticulture.
AB  - Working in agriculture and horticulture gives considerable job satisfaction. The
      tasks are often interesting; you can see the result of your own work, watch your
      crop grow and mature; you have an affinity with nature and can follow the changes
      in the seasons. However, today it is a dangerous work environment fraught with
      occupational injuries and diseases due to hazardous situations and to
      physiological, physical, biological, chemical, psychological, and sociological
      factors. The ongoing rapid development may, on the other hand, bring about many
      changes during the next decades with more farmers and growers switching to
      organic production. Moreover, increased awareness of animal welfare also may lead
      to improved working conditions. Large-scale operations with fewer family-operated
      agricultural businesses might mean fewer injuries among children and older
      farmers. A consequence of large-scale operations may also be better regulation of
      working conditions. The greater use of automation technology eliminates many
      harmful working postures and movements when milking cows and carrying out other
      tasks. Information technology offers people the opportunity to gain more
      knowledge about their work. Labeling food produced in a worker-friendly work
      environment may give the consumers a chance to be involved in the process.

PMID- 17208685
TI  - Shrimp culture in Thailand: environmental impacts and social responses.
AB  - Black tiger shrimp (Penaeus monodon) is a major aquaculture commodity among
      Southeast Asian producers and remains a popular food export world-wide. Food
      brokers in Japan and the United States purchase huge quantities of these farmed
      shrimp and return significant foreign exchange earnings to developing nations
      like Thailand, a major producer and exporter since the early 1990s. However,
      coastal areas cannot sustain intensive shrimp farm production and local growers
      often end up in debt. Can the needs of farm communities around the world be
      suitably met when they join into a corporate-managed and export-oriented food
      system? What are the sustainable benefits and eventual costs to susceptible
      localities? The shrimp industry in Thailand reveals the difficult terrain to
      cross and powerful obstacles to overcome if authentic sustainable development is
      to be realized.

PMID- 17208687
TI  - Working to give justice a chance--interview with Kim Bobo. Interview by Beth
      Rosenberg.

PMID- 17208686
TI  - A bittersweet report from a New Orleans sugar refinery: working conditions and
      labor-management relations deteriorate together.
AB  - At the invitation of the president of United Food and Commercial Workers (UFCW)
      Local #1101, which represents workers at the Domino sugar refinery in Arabi,
      Louisiana, we met with several union members in the fall of 1998. Our purpose was
      to investigate workers perceptions of health and safety conditions in the plant
      and offer assistance in the amelioration of problems. We conducted in-person
      interviews, each lasting approximately 30 minutes, with the local union president
      and twelve members selected by the president.

PMID- 17208688
TI  - Workplace violence: a policy statement.

PMID- 17208689
TI  - Comments of the American Public Health Association on OSHA's proposed ergonomics
      standard.

PMID- 17208693
TI  - The once and future threat of the petrochemical industry to the world of life.
AB  - In the last 50 years, the petrochemical industry has massively introduced
      thousands of synthetic organic chemicals into the environment, only recently
      acknowledging that most of them are hazardous to living things. The industry has
      unwittingly appropriated from the living world its once-exclusive capability to
      produce organic chemicals, but has created substances, such as DDT, dioxin, and
      PCBs, that do not occur in living things and are therefore untested by the long
      course of evolution. Now, transmuted into biotechnology, the industry is making
      the same mistake. This time, again unencumbered by precautionary testing, it is
      creating transgenic organisms that are incompatible with the natural systems of
      inheritance. Once again, an informed public is needed to prevent an ill-conceived
      industrial venture far more threatening than the one that we are still struggling
      to remedy.

PMID- 17208694
TI  - Describing community health risks: can epidemiology be improved?
AB  - Environmental threats are one of the highest concerns of communities seeking to
      improve public health. University researchers seek to assist communities with
      these concerns by providing technical expertise. But these community-science
      collaborations are often frustrating to both parties. Communities often find that
      the scientific studies have not proven what they believe the problem to be, while
      scientists often feel at least pestered, if not manipulated, by the dirty
      politics of the community. This paper investigates the proposition that
      environmental scientists must learn to combine their quantitative studies with
      qualitative views on the community and its health, if their studies are to be
      useful and indeed even fully accurate. The goal of the presentation is to explore
      changes in the methods of one particular field, environmental epidemiology, that
      might make it more relevant to current environmental debates. After a brief
      history of the field, limitations in the current practice of epidemiology are
      presented. These can be grouped under two headings: an over-emphasis on
      quantitative results, and an underestimation of uncertainties in study results.
      Some suggestions are given for changes that might address these problems, and
      make epidemiology more useful for citizens and policy-makers. These are: 1. nest
      quantitative results in qualitative descriptions of study populations; 2. fit two
      different kinds of statistical models one very simple, the other quite complex;
      3. conduct sensitivity analyses; and 4. use precautionary guidelines for causal
      inference. It is concluded that environmental epidemiology serves a particular
      societal function; which is to inform citizens and policy makers about
      environmental hazards that, perhaps, should be the subject of legal and economic
      interventions. For this reason, methods could be changed to improve the fit of
      the science to this function. There remains, however, much to be done to revise
      and refine this perspective, and to make the suggestions sufficiently specific
      that they can be put into practice.

PMID- 17208695
TI  - Low-hanging fruit: social values and industry discretion in toxics use reduction
      policy.
AB  - In this article, we examine the implementation of an innovative environmental
      policy, the Massachusetts Toxics Use Reduction Act (TURA), which seeks to shift
      environmental intervention into production through the reduction of toxics use.
      TURA attempts to promote change by requiring facilities to undertake toxics use
      reduction planning as a way to identify opportunities for reducing hazardous
      chemical use, and the creation of a new third-party policy actor known as the
      toxics use reduction planner to monitor facility compliance. We draw upon
      interviews with toxics use reduction planners to highlight the limited nature of
      change actually wrought by toxics use reduction planning. The article concludes
      that industry preferences, while not wholly inconsistent with change, have
      largely determined the way in which this public policy has been implemented.

PMID- 17208696
TI  - Indicators of sustainable production: a new tool for promoting business
      sustainability.
AB  - This paper proposes a new tool for promoting business sustainability--indicators
      of sustainable production. It discusses the business case for sustainable
      development and introduces the concept of sustainable production as a way to
      equally address different aspects of production (environmental and occupational,
      social and economic). Indicators are suggested as a tool for operationalizing
      this concept and their objectives, scope, and desirable qualities are outlined.
      The paper concludes with some recommendations for developing indicators of
      sustainable production.

PMID- 17208697
TI  - Robbers aboard: workplace violence and (in)security in public transport in
      Salvador, Brazil.
AB  - This paper examines the impact of violent crime on the working conditions,
      health, and security of bus drivers and bus conducters in the public transport
      system of Salvador, Brazil. The research included in-depth extensive interviews
      with workers, labor union officials, users, managers, and police. The typical
      social profile of offenders is as poor, unemployed youths, mostly without
      criminal records, seeking easy money mainly for leisure pursuits. Takes are
      minimal. We observed a pattern of bus robbery as a psychological power-game which
      for the bus workers, apart from physical injuries and fatalities, generates fear,
      identity conflicts, tense relations with users, and labor conflicts regarding the
      recuperation of stolen fares and worker and user security issues. We outline and
      evaluate the efficiency of security measures, including the use of lethal force
      by police.

PMID- 17208700
TI  - An honor for Richard Clapp.

PMID- 17208701
TI  - Exploring health, safety and environment in central and Eastern Europe: an
      introduction to the European Centre for Occupational Health, Safety and the
      Environment (ECOHSE).
AB  - This article traces the development of the European Centre for Occupational
      Health, Safety and the Environment (ECOHSE) at the University of Glasgow. ECOHSE
      recently has been designated a Thematic Network by the European Union which is
      providing administrative support through 2004. The de facto de-regulation that
      accompanied emergent capitalism in Eastern Europe created opportunities for
      exploitation of the work force. Voluntary efforts of a loose network of
      occupational and environmental health academics led to a series of yearly
      conferences to discuss these problems and the lack of research about them. Then,
      in 1999, a more formal organization was established at Glasgow to pursue
      continuity and funding. The first occupational and environmental health
      conference under ECOHSE was held last year in Lithuania, and selected
      presentations of that meeting are offered in this journal. A second ECOHSE
      conference will be held this fall in Romania.

PMID- 17208702
TI  - Participatory/problem-based methods and techniques for training in health and
      safety.
AB  - More knowledgeable and trained people are needed in the area of occupational
      health, safety, and environment (OSHE) if work-related fatalities, accidents, and
      diseases are to be reduced. Established systems have been largely ineffective,
      with few employers taking voluntary measures to protect workers and the
      environment and too few labor inspectors available. Training techniques using
      participatory methods and a worker empowerment philosophy have proven value.
      There is demonstrated need for the use of education for action, promoting the
      involvement of workers in all levels of decision-making and problem-solving in
      the workplace. OSH risks particular to women s jobs are virtually unstudied and
      not addressed at policy levels in most countries. Trade unions and health and
      safety professionals need to demystify technical areas, empower workers, and
      encourage unions to dedicate special activities around women s jobs. Trained
      women are excellent motivators and transmitters of safety culture. Particular
      emphasis is given to train-the-trainer approaches.

PMID- 17208703
TI  - The impact of information and communication factors on mitigation of workers
      health in the Chernobyl zone, 1986-1990.
AB  - Several important features of the Chernobyl disaster make it an outstanding event
      among the industrial accidents in the world s history. We want to draw the
      readers attention to three of them: 1) Chernobyl involved severe occupational
      injuries and caused chronic disorders in an unprecedented number of mitigation
      workers; 2) the health problems in question cannot be attributed solely to the
      specific radiation injury in the zone 1 ; and 3) the Chernobyl disaster has been
      a unique communication (media, in particular) event in terms of its international
      coverage, impact, and the controversies it has generated. The purpose of this
      article is to trace the links between these peculiarities of the accident and to
      suggest a framework for relating the communication and information factors to the
      health condition of the people who were occupationally involved in the Chernobyl
      disaster mitigation. We also will propose a number of ideas about how the factors
      in question can be managed within the Chernobyl disaster mitigation policy, which
      at present is critically shaped by the post-Soviet political, economic, and
      cultural context.

PMID- 17208704
TI  - Case study on chronic organophosphate poisoning.
AB  - Ernest and Leslie Rea, two farmers in their mid-fifties, contacted their local
      County Agricultural Extension Office in Cape May, New Jersey, regarding health
      problems associated with their use of pesticides. They were referred to Dr.
      Hamilton and the Environmental and Occupational Health Sciences Institute (EOHSI)
      clinic for consultation and evaluations. They were diagnosed with chronic
      intoxication of organophosphate pesticides. Recommendations were made to decrease
      health risks in the farming operations. These included the usage of personal
      protective equipment while handling or applying pesticides, transportation of
      pesticides in a separate trailer behind the farm truck, and construction of
      separate storage areas for herbicides, insecticides and fungicides. A separate
      wash site was also constructed for use at the end of the work day. Compliance
      with these strategies resulted in improvements in health for both farmers.

PMID- 17208705
TI  - Environmentalism unbound: reconnecting and re-envisioning movements for change.
AB  - Disputes over environmental discourse have generated divergent pathways and
      discordant messages over the last three decades. An examination of them becomes a
      study of environmentalism s roots. The workplace is shown as a hidden and often
      discounted arena of debate about what constitutes an environmental issue. The
      triumph of the productionist and limitless consumption views helped to establish
      a focus on environmental change as a form of consumer action. Since the 1970s
      though, new forms of environmental discourse and action both community- and
      production-related have sought to shift the terrain. The possibility of becoming
      a broader, more socially inclusive movement capable of challenging the very
      structure and logic of capitalist social order is possible again, including the
      ability to identify new strategies for action. Overcoming the work/environment
      divide is perhaps the most contentious question facing the future of the
      environmental and labor movements. New approaches, including developing a
      community of interests, revaluing work, and developing an ethic of place (with
      urban, industrial, and global forms), require that the social and the ecological
      become joined in the construction of a common vision. When any environmental
      issue can be seen as socially determined, then environmentalism s great task will
      be to see itself as a primary agent of social change.

PMID- 17208706
TI  - From natural resources to natural assets.
AB  - This article examines the scope for strategies to build natural assets in the
      hands of low-income individuals and communities. Natural assets include sources
      of raw materials such as forests and fisheries, and the airsheds, lands, and
      water bodies that provide environmental sinks for the disposal of wastes. These
      resources become assets when people have rights to access their benefits. Four
      strategies for natural asset-building are identified: investment to increase the
      total stock of natural assets; redistribution to transfer natural assets from
      others; internalization to increase the ability of the poor to capture benefits
      generated by their stewardship of natural assets; and appropriation to establish
      rights for the poor to open-access resources. Building on the democratic
      principle that all individuals have equal rights to clean air, clean water, and
      other common heritage resources, these strategies simultaneously can advance the
      goals of poverty reduction, environmental protection, and environmental justice.

PMID- 17208707
TI  - An appeal for justice for Bhopal's victims.

PMID- 17208712
TI  - Trade policy and public goods.
AB  - The World Trade Organization (WTO) was formed in 1994 as the first multilateral
      trade organization with enforcement authority over national governments. A
      country's domestic standards cannot be more restrictive than international
      standards for trade. WTO seeks to "harmonize" individual domestic policies into
      uniform global standards and encompasses trade-related aspects of health, public
      safety, and environmental protection. These issues are transnational and pose
      enormous challenges to traditional governance structures. Most governments are
      not equipped to manage problems that transcend their borders. Moreover,
      international governance in social issues--with the possible exception of public
      health--is still in its infancy. Many groups are concerned that local public
      interests will be subjugated to global corporate interests. The article looks at
      the social ramifications of world trade policy and concludes that world trade
      must be balanced with sustainable environments and human health.

PMID- 17208713
TI  - Work security in a global economy.
AB  - Work security is a fundamental right of all working people. After World War II,
      the welfare state became an intrinsic part of the "Golden Age" of capitalism, in
      which universal prosperity seemed attainable. Workers' organizations frequently
      played a crucial role in policy decisions that promoted full employment, income
      stability, and equitable treatment of workers. Today's world order is quite
      different. Globalization in its present form is a major obstacle to work
      security. Globalization is not simply a market-driven phenomenon. It is a
      political and ideological movement that grants authority to capital over
      governments and labor. This transfer of authority hinders national efforts to
      promote work security and may impact the well-being of communities worldwide. In
      the absence of domestic autonomy, international labor standards are needed to
      protect social welfare. They should be geared toward curbing unemployment,
      poverty, and social exclusion in the global economy. The article looks at three
      initiatives to promote global work security.

PMID- 17208714
TI  - The right to health.
AB  - Does the global trading system operate to the detriment of human rights? Some
      people think so. Many argue that trade policy interferes with a nation's capacity
      to develop its own human rights policies in the areas of health, nutrition, and
      medical services. This article examines that contention by studying how World
      Trade Organization (WTO) rules limit a country's ability to uphold the right to
      health for its citizens and suggests ways that human rights norms and mechanisms
      can be employed as counterweights to socially harmful WTO polices. The author
      concludes that most commentators agree that human rights are inalienable and thus
      would prevail in a judicial setting and that human rights mechanisms have been
      underused by proponents of public health.

PMID- 17208715
TI  - Sustainable development: a trade union perspective.
AB  - Sustainable development has become an important issue for trade unions around the
      world, but progress on sustainable development has been slow. Agenda 21, which
      came out of the 1992 UN Conference on Environment and Development in Rio de
      Janeiro, called on workers and trade unions to assume an active role. The
      International Confederation of Free Trade Unions (ICFTU) and the Trade Union
      Advisory Committee (TUAC) to the Organization for Economic Co-Operation and
      Development (OECD) became influential players who represent more than 155 million
      members in 148 countries and territories. The implementation of Agenda 21 has
      been hampered by bureaucratic gridlock--a situation that trade unions propose to
      overcome through innovative strategies on workplaces and workers. They realize
      that sustainable development cannot take place without radical changes in
      production and consumption. Globalization is creating opulence on the one hand
      and grinding poverty on the other. ICFTU and TUAC propose a new "world order"
      that includes democratic decision-making, popular accountability, transparency,
      and local control. They have proposed priorities, outlined in this article, for
      an international approach to sustainable development.

PMID- 17208716
TI  - Corporate citizenship: Statoil.
AB  - Open markets alone do not guarantee equitable and sustainable development. Income
      disparities are growing both within and between countries to the extent that the
      marginalization of the poor has become a key challenge of globalization. To meet
      this challenge, the global community must address the governance gap between
      global finance/economics and local or national politics in world affairs. This
      article discusses how globalization is shaping Statoil's approach to corporate
      citizenship. The Norwegian firm, with 17,000 workers in some 25 countries, is one
      of the major net sellers of crude oil and supplies Europe with natural gas.
      Statoil maintains that corporations can contribute to global governance by
      conducting business in a manner that is ethical, economically viable,
      environmentally sound, and socially responsible. This contribution can be
      achieved through development partnerships with national governments, multilateral
      institutions, and nongovernmental organizations. Norway's Statoil ASA is one of
      the world's largest net sellers of crude oil and a major supplier of natural gas
      to Europe. It is the leading Scandinavian retailer of petroleum and other oil
      products. Statoil employs approximately 17,000 workers and operates in 25
      countries.

PMID- 17208717
TI  - Renewing governance.
AB  - Globalization's profound influence on social and political institutions need not
      be negative. Critics of globalization have often referred to the "Impossible
      Trinity" because decision-making must 1. respect national sovereignty, 2. develop
      and implement firm regulation, and 3. allow capital markets to be as free as
      possible. To many, such goals are mutually exclusive because history conditions
      us to view policy-making and governance in traditional molds. Thus, transnational
      governance merely appears impossible because current forms of governance were not
      designed to provide it. The world needs new tools for governing, and its citizens
      must seize the opportunity to help develop them. The rise of a global society
      requires a greater level of generality and inclusion than is found in most policy
      bodies today. Politicians need to re-examine key assumptions about government.
      States must develop ways to discharge their regulatory responsibilities across
      borders and collaborate with neighboring jurisdictions, multilateral bodies, and
      business. Concepts such as multilateralism and tripartism show great promise.
      Governments must engage civil society in the spirit of shared responsibility and
      democratic decision-making. Such changes will result in a renewal of the state's
      purpose and better use of international resources and expertise in governance.

PMID- 17208718
TI  - The need for global environmental health policy.
AB  - The world economy has been growing by an average of 3.5% a year. Continued global
      development is sustainable if overall social assets remain constant or rise over
      time, including manufactured, human, and environmental capital. Sustainable
      development requires that society not decrease its overall assets. But
      unregulated global trade may result in long-term loss of environmental capital.
      Multilateral governance is needed. Classical business models tend to view
      environmental damage as an externality--an impact on a third party's welfare that
      is neither compensated nor appropriated. The Rio Declaration on Environment and
      Development clearly states that economic development must err on the side of
      environmental integrity. Whereas UN Environmental Program policy requires
      precaution in the face of scientific uncertainty, World Trade Organization policy
      requires scientific certainty before precaution can be used. The conflict is
      obvious. In fact, there is gross lack of policy coordination across institutions.
      This article looks at some environmental strains and concludes that trade policy
      must address all aspects of human welfare, not merely the economic.

PMID- 17208719
TI  - The global trade and public health nexus: the role of WHO.
AB  - The globalization of the world economy and changing trade relations have major
      public health implications. The trading community's foremost concern has been to
      minimize the perceived interference by health issues with freer trade. The
      exploration of how trade liberalization is affecting determinants of health is
      well underway and has attracted worldwide attention. Importantly, the
      professional community has engaged trade-related organizations to ensure proper
      representation of public health interests. The UN's World Health Organization
      (WHO) is mandated "to act as the directing and coordinating authority on
      international health work." This responsibility obligates it to address major
      trends that impinge on human health. The article suggests areas of study to
      strengthen the WHO's role and urges that it reevaluate its traditional focus on
      working with the health ministries of its member states. In many ways, public
      health is still playing "catch up" with powerful vested interests. New tools and
      strategies are needed.

PMID- 17208720
TI  - Beyond trade: taking globalization to the health sector.
AB  - The pace of globalization has brought the world to the brink of a new era in
      international relations. While the world has outgrown traditional mechanisms for
      addressing global issues, it has not yet developed new forms of effective
      governance. This temporary void poses threats and enormous opportunities. The
      public health sector will play a crucial "formal" role--that is, carried out by
      existing bodies such as WHO and the UN. But WHO does not necessarily represent
      the full spectrum of views and its members necessarily work, to some degree, for
      separate national interests. The formal dimension must be supplemented.
      Globalization is not synonymous with lack of regulation. Many responsible
      businesses would welcome a transparent and universally applied regulatory regime
      to prevent a race to the lowest standards. The economic benefits of globalization
      may hit a glass ceiling if societies outside the global economy become
      progressively poorer and less healthy. The business community is recognizing that
      good health is essential for economic growth and social stability. Globalization
      may cause millions to migrate for economic opportunity. The private sector's
      forward-thinkers recognize the health threats of migration and are beginning to
      view global health promotion as a means to ensure optimal market access.

PMID- 17208721
TI  - WTO confidential: the case of asbestos.
AB  - The World Trade Organization (WTO), established in 1995, adjudicates "trade
      disputes" between member nations in cases with human rights, cultural,
      environmental, and public health significance. Throughout the resolution process
      and even after a case's conclusion, little of what happens is made accessible to
      the public. However, it is one thing to criticize the WTO for its lack of
      transparency from outside the process and another to critically examine what was
      withheld from disclosure and what dangers that presents. This is the inside story
      from a scientific adviser to one party in a WTO case, who analyzes what happened
      from a public health point of view. The analysis concludes that the public health
      justification for banning asbestos was accepted in the end by WTO economists,
      despite the WTO's bias in favor of the party (Canada) making the free trade
      challenge (to public health legislation), despite the WTO's lack of expertise in
      science, medicine, engineering, and public health, and despite important
      erroneous statements made to the WTO under the cover of confidentiality. The case
      nevertheless illustrates that the WTO's threat to national sovereignty could
      never withstand the light of day if the limitations and dangers of the process
      were open for all to see.

PMID- 17208722
TI  - Privatizing the welfarist state: health care reforms in Malaysia.
AB  - In Malaysia, the shifting balance between market and state has many nuances.
      Never a significant welfare state in the usual mold, the Malaysian state
      nonetheless has been a dominant social and economic presence dictated by its
      affirmative action-type policies, which eventually metamorphosed into state-led
      indigenous capitalism. Privatisation is also intimately linked with emergence of
      an indigenous bourgeoisie with favored access to the vast accumulation of state
      assets and prerogatives. Internationally, it is conditioned by the fluid
      relationships of converging alliances and contested compromise with international
      capital, including transnational health services industries. As part of its
      vision of a maturing, diversified economy, the Malaysian government is fostering
      a private-sector advanced health care industry to cater to local demand and also
      aimed at regional and international patrons. The assumption is that, as
      disposable incomes increase, a market for such services is emerging and citizens
      can increasingly shoulder their own health care costs. The government would
      remain the provider for the indigent. But the key assumption remains: the growth
      trajectory will see the emergence of markets for an increasingly affluent middle
      class. Importantly, the health care and social services market would be
      dramatically expanded as the downsizing of public-sector health care proceeds
      amid a general retreat of government from its provider and financing roles.

PMID- 17208723
TI  - Work security impacts in developing countries: India.
AB  - Given the rapid pace of globalization, newly industrialized countries cannot
      adequately protect workers from emerging hazards. Only 5-10% of workers in
      developing countries have access to occupational health services. Work-related
      health problems are exacerbated by a scarcity of resources, socioeconomic
      dislocation, and poor general health status. The author considers the case of
      India and looks at its background in occupational safety and health (OSH)
      regulation, national health policy, and recent experience. He notes the decline
      in trade unions and rise of hazardous industries, and presents a case study of
      the situation in the state of Delhi. He concludes that the progress of OSH has
      stalled since economic reform. The high rate of injury and illness is a bad omen
      for productivity. Lowering the guard on safety and health will ultimately harm
      the businesses that currently seek to profit from it. The well-being of workers
      may deteriorate further if poor enforcement and widespread ignorance of OSH
      persist. Labor standards must be reevaluated and responsible legislation must be
      developed. Training and nutrition subsidies should be offered to increase
      productivity and improve worker health.

PMID- 17208724
TI  - Occupational safety and health on the U.S.-Mexico border.
AB  - A number of trade agreements were adopted in the 1990s that promised economic
      growth for Mexico. The most significant was the North American Free Trade
      Agreement (NAFTA), which promotes open trade between Mexico, the United States,
      and Canada. Like WTO, NAFTA focuses on the economic aspects of trade.
      Occupational safety and health issues were not specifically addressed by NAFTA.
      Despite the presence of domestic regulatory systems, concerns over working
      conditions persist on both sides of the U.S.-Mexico border and the workforces
      face similar health problems. The upsurge in trade between the United States and
      Mexico must be accompanied by an international commitment to occupational safety
      and health in border areas. If government agencies cannot or will not intervene
      to reduce rates of workplace injuries and illnesses, civil coalitions must assume
      this role.

PMID- 17208725
TI  - Second thoughts about silicosis.
AB  - The decisions that a society makes can lead to workplace and environmental
      illness and injury. After some years working on the hazards related to exposures
      to silica and studying interventions to prevent them, the author assesses the
      results of her efforts. She succeeded in getting silica added to the list of
      substances regulated under the Massachusetts Toxics Use Reduction Act, though not
      easily. And she found some of the obstacles to doing so nonsensical or stubbornly
      resistant. The next step, she foresees, is leveraging that outcome to ban or
      limit the use of sand in blasting operations. But in the course of her work, she
      also has seen that interest in mitigating the dangers of silica, which is strong
      among medical and public health professionals who rightfully argue that nobody
      should be made ill today by this completely preventable problem, is tepid among
      the workers most affected by it. Although they understand the dangers of silica,
      it is not their main concern, and she understands why. In future work, she
      concludes, it may be more worthwhile to allow the community of workers to set the
      agenda and to help them achieve their goals.

PMID- 17208726
TI  - Jim Tramel: radical Southerner for social justice, rip.
AB  - Jim Tramel, who died in December 2002, spent his life working for social justice.
      Here, friends and colleagues remember him as a Southern radical who organized on
      behalf of battles against classism, racism, and sexism.

PMID- 17208727
TI  - Occupational safety and health.
AB  - The 2002 elections put worker health and safety in a deep hole. The
      administration's core strategy on safety and health wraps vague, moderate
      rhetoric around hard-right policies which cater to the most anti-worker factions
      of the business community. The first significant act of the Bush administration
      in the labor arena, in March 2001, was signing business-sponsored legislation to
      wipe out the Occupational Safety and Health Administration's (OSHA's) ergonomic
      standard. The administration also proposed to cut OSHA-funded worker training and
      standard-setting, appointed the organizer of the business anti-ergonomics
      campaign as solicitor of labor, and proposed deep budget cuts for worker training
      and standard-setting, while maintaining industry friendly assistance programs.
      Specific to the United Auto Workers (UAW), OSHA withdrew its announced effort to
      set a new standard for metalworking fluids, as well as many other new standards.
      Soon after these actions, the Senate changed hands and we were able to stop the
      bleeding. But as a result of the 2002 elections, conservatives control the entire
      Congress and will try these attacks all over again.

PMID- 17208728
TI  - Joint occupational and environmental pollution prevention strategies: a model for
      primary prevention.
AB  - Occupational and environmental health issues are not always considered
      simultaneously when attempting to reduce or eliminate hazardous materials from
      our environment. Methods used to decrease exposure to hazardous chemicals in the
      workplace often lead to increased exposure in the environment and to the
      community outside the workplace. Conversely, efforts to control emissions of
      hazardous chemicals into the environment often lead to increased exposure to the
      workers inside the plant. There are government regulations in place that ensure a
      safe work environment or a safe outside environment; however, there is little
      integration of both approaches when considering the public's health as a whole.
      This article examines some of the reasons behind this dichotomy, focusing on the
      regulatory and policy frameworks with respect to workplace and environment that
      have resulted in the inability of the Occupational Safety and Health
      Administration (OSHA) and the Environmental Protection Agency (EPA) to coordinate
      their efforts to protect public health. The components of the Pollution
      Prevention Act and its potential to serve as a model for integrating occupational
      and environmental health are discussed. Limitations regarding enforcement of
      pollution prevention, as well as its disconnection from the work environment are
      equally highlighted. The article finishes by examining the barriers to
      integrating the occupational and environmental health paradigms and the promotion
      of primary prevention in public health.

PMID- 17208729
TI  - Whose scientific method? Scientific methods for a complex world.
AB  - Critics of the precautionary principle assail it for calling for action before
      science establishes unquestionably that a substance causes harm. They claim
      theirs is the viewpoint of the "scientific method." But the conflict is not
      between science and antiscience but rather between different pathways for science
      and technology; between a commodified science-for-profit and a gentle science for
      humane goals; between the sciences of the smallest parts and the sciences of
      dynamic wholes. This article addresses the social construction of scientific
      production and the pattern of strengths and weaknesses to which it leads. The
      author offers proposals for a more holistic, integral approach to understanding
      and addressing environmental issues.

PMID- 17208730
TI  - Precaution, environmental science, and preventive public policy.
AB  - The Lowell Center for Sustainable Production has sought to engage scientists,
      policy-makers, advocates, and students in a broad public discussion about whether
      the tools and methods of environmental science and its integration in policy are
      adequate to address complex, highly uncertain environmental and health risks. It
      did so in an International Summit on Science and the Precautionary Principle and
      a recent collection of analyses stemming from the summit. Here, the author
      summarizes some summit recommendations to overcome barriers and build momentum
      for a vision for science and policy that better reflects uncertainty and
      complexity in natural systems. Appended is a summit statement on the subject.

PMID- 17208731
TI  - The burden of emissions restrictions.
AB  - Models with time horizons of 100 years are customarily used to predict
      anthropogenic greenhouse gas emissions. Historical evidence indicates that over
      this time span the current consumption patterns in developing countries are
      likely to change and converge to the present patterns in developed countries.
      This study deals with modeling this type of convergence in consumption patterns
      within the MIT Emission Prediction and Policy Analysis Model (EPPA) framework. We
      find that the differences in the model with static consumption-function
      coefficients from that in the model with dynamic coefficients have significant
      implications for the costs of emissions restrictions in developing countries,
      even though the regional emissions profiles are virtually the same. Our results
      suggest that the costs of emissions restrictions in developing countries would be
      higher if the changes in consumption patterns are taken account of than if they
      are ignored in the simulation model.

PMID- 17208733
TI  - Secondhand smoke hurts everyone.
AB  - Below is testimony in support of a city-wide worksite smoking ban presented by
      NYCOSH (The New York Committee on Occupational Safety and Health) to the New York
      City Council on November 12, 2002.

PMID- 17208732
TI  - What do regions want?: A case study of university-community relations.
AB  - We hear more and more about the necessity of "sustainable regional development"
      as an alternative to and defense against globalization. While we certainly agree
      with this notion, we ask what might prevent it from becoming yet another "top
      down" development scheme with good intentions but dubious results. We would argue
      that no road to development is sustainable if it is not deeply democratic and
      reliant on an informed, concerned public; the expressed needs of the public must
      be an essential aspect of regional development. Our focus here is on the
      university, the main supplier of the experts and technologies utilized by the
      undemocratic processes of globalization, but it might also be a partner in a
      democratic process of regional sustainable development. To do this, however,
      experts in academia must resist the temptation to assume they know what is best
      and work in concert with community forces to define and create sustainable
      development. To put it simply, if experts and planners in the university want to
      know what a region wants and needs, they have to ask. What follows is a report on
      the experience of one university's attempt to do just that.

PMID- 17208734
TI  - Cancer Battles and the Sleep of Reason policy and science need not be related.
AB  - Cancer Battles and the Sleep of Reason is an inquiry into the role of scientific
      experts in environmental health policy-making. The article first establishes two
      propositions: that there is no necessary relationship between science and
      environmental health policy; and that risk assessment is not the only science of
      environmental health. It then asks the question: why should policy-makers consult
      the scientific experts? If experts are to be consulted, there will have to be
      some way of grading experts as to the quality of their advice and their
      usefulness to policy-makers. A mode of grading experts is provided in
      Environmental Cancer--A Political Disease? by S. Robert Lichter and Stanley
      Rothman. But the arguments in this book are shown to be worthless; the book fails
      to address the underlying issue of why the experts should be consulted at all.
      The article concludes that experts are to be consulted whenever policy-makers
      consider their advice to be essential or useful. There is nothing in the
      scientific disciplines that entrenches them in the policymaking process; the
      opinions of scientific experts have no special place in environmental health
      policy.

PMID- 17208735
TI  - Playing the press for a fool.

PMID- 17208736
TI  - Occupational health and safety in the real "new economy".
AB  - The so-called New Economy of the 1990s failed to deliver its promise of clean
      work and huge leaps in productivity; what really happened was an intensification
      of economic pressures on marginal workers. The effects on employment include:
      increasing income disparities, fewer jobs that lead to viable career tracks, less
      secure employment, longer working hours, and higher risk of uncompensated
      unemployment. Workers who are either newly entering the workforce or who do not
      have the training or skills to trade up in employment are under pressure from
      falling middle- and lower-income wage scales and increasing income disparities.
      Their opportunities are increasingly limited, whether by seeking better-paying
      jobs with other employers or moving up the now-shortened ladder at one employer.
      They face a declining choice of employment opportunities and well-paying jobs
      that tend to be concentrated in residual dangerous work in manufacturing or
      service sub-sectors that are often small or economically marginal. These forces
      appear to be pushing workers into accepting jobs in the diminishing but still
      substantial number of jobs that remain that are dirty and dangerous, as
      illustrated by the extreme example of McWane Pipe. Those who are forced into
      these dangerous jobs will once again most likely be the poorly prepared, the new
      entry, the recent immigrant, and the illiterate worker. National occupational
      injury statistics may conceal the experience of these marginal industries by
      aggregating them into much bigger economic sectors. To understand this
      phenomenon, we need studies that examine the social choices and tradeoffs
      involving employment from the point of view of the worker and develop a means of
      monitoring these tradeoffs.

PMID- 17208737
TI  - Sewage sludge draws new attention.

PMID- 17208738
TI  - Health care facilities in the Ukraine.

PMID- 17208739
TI  - Family and medical leave act: unresolved issues.
AB  - The United States' Family and Medical Leave Act (FMLA) of 1993 was an effort to
      provide national support for families attempting to balance the demands of the
      workplace and the need to care for a new child, one's own health, or an ill
      child, spouse, or parent. It is seriously limited, however, in terms of its
      accessibility for many workers. We briefly compare the FMLA to the substantially
      broader policies of Western European countries. We highlight its reported
      benefits to workers but document disparities in employees' use of the FMLA by
      gender, race, and income level. We evaluate whether employers' fears of higher
      costs were justified. We point out current challenges that may limit the FMLA
      further. We close by examining the range of alternative policies in effect at the
      state level and proposals that would address the current limitations of the FMLA
      and broaden its coverage.

PMID- 17208741
TI  - An interview with Peter Olney, labor organizer.

PMID- 17208740
TI  - The radiation exposure compensation act: what is fair?
AB  - In 1990 the U.S. Congress passed a law providing compensation to former uranium
      miners who became ill while the U.S. Government was the sole purchaser of
      uranium. Ten years later, in 2000, the law was amended to correct widely
      perceived problems. We reviewed the content of the Radiation Exposure
      Compensation Act (RECA) laws and regulations, cataloged complaints about the 1990
      law, compared the law to the scientific knowledge base in 1990 and in the
      present, reviewed the 2000 amendments to RECA, and drew lessons about how such
      compensation programs might be better structured. We concur with popular
      sentiment that the 1990 law had numerous flaws, the central one being that it
      failed to compensate many miners who by most other standards would have been
      deemed deserving. This problem arose through setting exposure criteria very high
      (at six to 15 times elevated risk), with a disproportionate burden placed on
      miners who had smoked. The additional burden on smokers was exacerbated by a very
      stringent definition of smokers (one pack-year in a lifetime). Federal
      compensation laws should prioritize payment to deserving claimants rather than
      excluding un-deserving claimants. Thus, a doubling of risk should be an upper
      limit for setting an eligibility threshold and a lower "significant contributory
      effect" standard could be considered more appropriate. Uncertainties in exposure
      and in dose response should be considered and resolved with a bias toward
      compensation. Beyond setting appropriate criteria, an active effort is needed to
      inform potentially eligible people and to assist them in qualifying; the
      eligibility criteria and the requirements for documentation should be appropriate
      for Native Americans and other cultural groups. Built-in evaluation mechanisms
      are needed for all compensation programs to assess whether they are meeting their
      stated objectives.

PMID- 17208742
TI  - Remembering Alan J. P. Dalton.

PMID- 17208743
TI  - Are we winning or losing the war on cancer? Deciphering the propaganda of NCI's
      33-year war.
AB  - The National Cancer Institute (NCI) and collaborating agencies have proclaimed
      great progress in the U.S. "war on cancer," while at the same time presenting
      more reasons for concern than celebration. We reviewed various documents and data
      files and found that incidence and mortality rates for all cancer sites combined
      remain higher than they were when the "war on cancer" was declared in 1971,
      despite very recent, modest decreases. The burden of the disease has risen from
      three million to nearly ten million people. Black Americans, men of all races,
      and other segments of the population disproportionately bear the burden of
      cancer. We also looked at data for malignant breast cancer and found that
      incidence rates increased 36% from 1973 to 2000, while mortality for all
      population groups combined declined slightly. Breast cancer mortality is 34%
      higher among black women than among white women, even though white women are
      generally more likely to get the disease. The $50 billion spent on the "war on
      cancer" over the last 33 years has yielded few gains. The NCI's resources must be
      refocused on preventing cancers we know how to prevent.

PMID- 17208744
TI  - Systems of safety and active worker-participation strategies for a safe
      workplace: the philosophical and structural underpinnings of the labor institute,
      and the Paper, Allied-industrial, Chemical And Energy Workers International
      Union, Accident Prevention Programs.
AB  - For the last ten years, The Labor Institute, in cooperation with the Paper,
      Allied-Industrial, Chemical and Energy Workers International Union (PACE) and
      several other international unions, has been training workers and managers to
      prevent accidents in the workplace using what we call a Systems of Safety (SOS)
      approach. We teach workers to identify major categories of safety systems and sub
      systems in the workplace and to assign a hierarchical prevention value to each
      category. The SOS approach enables workers to look beyond the simplest
      explanations for an accident to identify the full range of factors that
      contributed to the event. As a result, Systems of Safety training provides
      workers with an unparalleled opportunity to reduce the frequency and severity of
      in-plant accidents. Unfortunately, the full benefits of an SOS system cannot be
      realized in most workplaces as they are now organized. Our decades of experience-
      and a review of relevant literature--tell us that worker participation is the key
      to preventing accidents. Maximum accident prevention is only achievable through
      maximum worker participation. In most workplaces, hierarchical structures--and
      workers' internalization of that hierarchy--prevent full worker participation.
      This article will explore barriers to achieving maximum worker participation, and
      strategies for providing workers with some measure of control over the systems of
      safety that determine the level of safety at their work sites.

PMID- 17208745
TI  - 'Doctors by Fax' or cleaner production: the problem of prevention in post
      communist Hungary.
AB  - In 1989, approximately half of the medical visits in Hungary were to factory
      doctors. Two thousand physicians in the National Health Service were assigned to
      factories and all medical students served in factories as part of their training.
      There were certainly problems in the system, but workers preferred the factory
      doctors to other physicians based in communities or districts; and factory
      physicians knew about workplace hazards, knew what production processes looked
      like, and were mandated to deal with work environment problems as well as provide
      other kinds of patient care. With the reform of the National Health Service, the
      role of factory physician was eliminated, although companies could institute
      their own medical services (and sometimes employed the previous medical staff).
      Later legislation required companies to have access to occupational medical
      services, but critics have called the new system "Doctors by Fax." We discuss the
      adequacy of the new legislative requirements (including mandatory health and
      safety committees) and report on new issues in worker health and safety that have
      emerged post "reform." Finally, the possibility of linking the prevention of
      occupational disease and injury prevention to "cleaner production" in Hungary is
      discussed.

PMID- 17208746
TI  - Tobacco industry targeting of blue-collar workers.
AB  - Blue-collar workers, an important segment of the American workforce, smoke at a
      significantly higher rate than white-collar workers. While much has been written
      about tobacco industry targeting of other groups, little has been written about
      the industry's deliberate plan to addict blue-collar workers. For decades, the
      tobacco industry has targeted blue-collar workers. This article chronicles the
      industry's concerted drive and reveals some of its strategies to recruit,
      maintain, and expand its consumer base. It describes one labor organization's
      efforts to counter the industry's influence on blue-collar workers. This research
      justifies the continuation of aggressive anti-tobacco efforts by health workers
      and labor unions involved in tobacco education programs targeting blue-collar
      workers.

PMID- 17208748
TI  - Final declaration of the fourth World Parliamentary Forum in Mumbai, India,
      January 19, 2004.
AB  - The following comment addressing crises arising from globalized trade came out of
      a meeting between the World Parliamentary Forum and the World Social Forum in
      India in January 2004.

PMID- 17208747
TI  - Cutting the longline to extinction: new sea turtle campaign takes aim at
      industrial longline fishing and mercury-poisoned seafood.
AB  - Chanting "Get on the right track . . . stop killing the leatherback!," a festive
      protest of people of many ages dressed in colorful turtle costumes wound its way
      along the busy streets of San Francisco's Fishermen's Wharf. The action last
      October marked the launching of the Bay Area-based Sea Turtle Restoration
      Project's Save the Leatherback (www.savetheleatherback.com) campaign for a
      moratorium on longline fishing in the Pacific Ocean. Longline fishing in the
      Pacific kills tens of thousands of sea turtles annually to serve up swordfish,
      shark, and tuna poisoned with high levels of methylmercury for lucrative seafood
      markets in Japan, the United States, and Europe.

PMID- 17208749
TI  - Manifesto for sustainable investment: investing for a sustainable future.
AB  - Environmental, labor, and non-governmental organizations in Europe are waging a
      campaign for sustainable investment to hold members of the European Union to
      their pledges to work for sustainable development and sustainable societies. The
      comment explains how to achieve sustainability by taking action at many levels of
      society.

PMID- 17208751
TI  - Good Practice Guidelines for occupational health research funded by the private
      sector.
AB  - The role of the private sector in funding academic research is increasing and the
      well-developed guidelines for government-sponsored research do not apply to the
      academic-industry arena. Good Practice Guidelines for privately funded
      occupational health research are necessary. Industry sponsors and academic
      researchers belong to differing systems with differing goals and means to achieve
      and evaluate them. As a result, problems are inherent in the relationship.
      Guidelines would benefit industry by providing criteria against which industry
      funded research could be judged and evaluated. Guidelines would help university
      researchers assure that their work is examined and criticized on its merits. Such
      protection would foster quality research over the long term. Here, we consider
      the issues involved and explore questions that came out of a workshop convened
      under the auspices of the Centers for Disease Control and Prevention. When
      private funding is involved, university scientists have a professional
      responsibility to ensure that the integrity of researchers, subjects, and the
      research process is well protected. A body of experience allows us to create Good
      Practice Guidelines beneficial to all parties.

PMID- 17208752
TI  - An alternative to regulation in the control of occupational exposure to
      tuberculosis in homeless shelters.
AB  - Five million U.S. workers are exposed to TB in the course of their work each
      year. The occupational risk of exposure to TB at homeless shelters is
      particularly acute. TB rates among the homeless are estimated to be 150 to 300
      times the nationwide rate. The U.S. Occupational Safety and Health Administration
      (OSHA) responded to the risk to homeless shelter workers by proposing a
      regulation mandating that shelters take prescribed actions to identify shelter
      residents who represent a potential risk and to remove those residents from the
      homeless shelter environment. This article concludes that the risk of TB exposure
      within homeless shelter workers is best viewed as a public health problem rather
      than as exclusively a worker protection problem. Accordingly, in addition to
      seeking worker protections through regulatory controls, OSHA should seek to
      promote occupational health and safety through a public health response as well.

PMID- 17208753
TI  - Access to medical care for individuals with workers' compensation claims.
AB  - Experience at a publically funded occupational health clinical center in New York
      State suggests that patients with work-related illnesses often have great
      difficulty accessing diagnostic and treatment services. A study was designed to
      more quantitatively investigate the extent and nature of barriers to medical
      services for patients with Workers' Compensation claims. Medical practices from
      13 selected medical specialties were identified from telephone directories. The
      directories covered six areas encompassing almost all of a 15-county region. All
      practices from each selected specialty were contacted by phone and asked a set of
      standardized questions regarding patient acceptance policies. A number of
      barriers were identified by the survey including practices closed to new patients
      and practices closed specifically to patients with Workers' Compensation claims.
      Barriers also were found to be widespread among practices that did accept
      Workers' Compensation claims, primarily related to requiring a guarantee of
      payment prior to seeing the patient. The results were compared by medical
      specialty and geographic area. While the study showed some of the difficulties
      patients with occupational illnesses face attempting to access medical services,
      it most likely underestimated the extent of the problem. Attitudes and practices
      that impede access, but were not measurable, create additional barriers. Our
      study strongly suggests that policies that improve access to medical care for
      individuals with Workers' Compensation claims are necessary to better serve the
      needs of workers with occupational illnesses.

PMID- 17208754
TI  - Health and safety organizing: OCAW'S worker-to-worker health and safety training
      program.
AB  - In 1987, the Oil, Chemical, and Atomic Workers International Union (OCAW) was
      funded as one of the original eleven awardees of the Superfund Worker Training
      Program of the National Institute of Environmental Health Sciences. The OCAW,
      with the Labor Institute, developed a hazardous waste worker and hazardous
      materials emergency responder health and safety training program that was
      specific to its members in the represented industries. A social history is
      developed to explore a union-led, worker health education intervention. The
      program sought to develop worker-trainers who would conduct the training, using
      the Small-Group Activity Method, participate in curriculum development, and
      ultimately use health and safety training as a vehicle for identifying,
      developing, and mobilizing health and safety activists among the membership.
      Although the direction for this effort came from progressive leadership, it arose
      from the political economy of labor/management relations within specific
      industrial sectors.

PMID- 17208755
TI  - The work environment justice fund: five years of funding work environment justice
      in Massachusetts.
AB  - This article provides an assessment of the impact of five years of funding on
      work environment justice in Massachusetts. It first outlines the economic,
      historical, and political context in the 1990s in Massachusetts. Next, it
      describes the distribution of the Work Environment Justice Fund grants in detail
      by amounts presented, types of organizations and grants funded, and geographic
      representation of grantees. A discussion of the lessons learned from the work
      funded by the WEJF introduces a summary of major accomplishments of the grantees.
      The report concludes with recommendations for continuation and expansion of
      funding for grassroots work environment justice in Massachusetts.

PMID- 17208756
TI  - Workers' testimony on the proposed ergonomic standard.

PMID- 17208759
TI  - OSHA proposing to "wire" Hispanic immigrant workers for safety education? Not
      likely.

PMID- 17208760
TI  - Genomics, health, and society.
AB  - On June 27, 2001, the World Health Organization conducted hearings in Geneva for
      a Special Report on Genomics & Health. Initially intended as a document to
      address the ethical, legal, and social implications of the gathering genomics
      resolution (ELSI), the terms of reference of the report were significantly
      modified to give primary emphasis to a scientific and technological assessment of
      the implications of genomics for human health. The Citizens' Health Initiative,
      one of two NGOs invited to make submissions at these consultations, suggested
      that no less important than the scientific and technical assessment was a
      perspective which gave due attention to the social context and political economy
      of scientific/technological development and its deployment. The article below
      touches upon neglected health priorities of poor countries, intellectual property
      rights and patents, risk management, insurance and discrimination, and predictive
      (prenatal) testing, reproductive choice, and eugenics.

PMID- 17208762
TI  - Good moves for the great woods.

PMID- 17208763
TI  - "We remain unorganized and unaware of each other"--a rationale for building a
      national directory.

PMID- 17208764
TI  - Prevention of work-related cancers.
AB  - Work-related cancers are highly preventable. The primary responsibility for
      prevention rests not with the workers who are affected by cancers, but with the
      manufacturers and distributors of carcinogenic substances and the companies who
      use them. U.S. public policies of strict product liability and the Occupational
      Safety and Health Act of 1970 address the issue of responsibility. Workers,
      health care providers, and others also have important roles that complement
      employers' preventive efforts. The range of prevention strategies available
      includes ones that should be applied to prevent potentially carcinogenic
      substances from being marketed and distributed; others that apply in the
      workplace where potential carcinogens are used; and public policy interventions
      aimed at ensuring universal implementation of pre-market and workplace prevention
      strategies. Work-related cancer remains a large problem, even though strategies
      exist to identify carcinogens and prevent and control on-the-job exposures.
      However, preventive efforts by government and the society have stalled and a
      continuing lack of toxicity information shows inadequate societal commitment. The
      principal barriers to prevention of work-related cancers are political and
      economic rather than scientific and medical.

PMID- 17208765
TI  - Making materials matter.
AB  - For sustainability, it would be much more effective and economically efficient to
      focus on designing and using less hazardous materials. By paying more attention
      to the materials that we manufacture and use, we could pay less attention to
      their impacts on people and the environment. The environmental costs of materials
      show up in damage from materials extraction, pollution, energy consumed, and
      waste material disposal. The model on which the materials management system is
      based is flawed. Future systems must be cyclical ones of sustainable managed
      material flows that conserve resources and minimize dissipation. Material
      recycling and reuse must be primary components, along with new extraction,
      harvesting, and treatment practices. Needed are new policies that promote human
      health and environmental quality, as well as economic efficiency and product
      effectiveness. The policies may be either public or private, but they must be
      integrative and focused on the full life cycle of materials. This sustainable
      materials economy will require new information systems, re-direction of materials
      markets, reconfiguration of corporate missions and designs, changes in government
      policies, and public engagement.

PMID- 17208766
TI  - Organizational downsizing: implications for the health of survivors.
AB  - Public health has a long-standing interest in the adverse consequences of
      unemployment and job loss upon the physical and emotional health of those who
      lose their jobs. In recent years, the emergence of organizational downsizing as a
      commonplace phenomenon directs attention to an entirely new area of concern: the
      impact of downsizing on those who keep their jobs and continue to work in the new
      work environment. In this article, we examine the multi-dimensional ways in which
      downsizing affects the survivors of downsizing and changes their working
      conditions, social relationships, and emotional well-being. We draw upon
      qualitative results from research with survivors of downsizing undertaken by the
      U.S. Department of Energy to highlight survivors' own accounts of the downsizing
      experience. These experiences suggest that a greater voice in workplace affairs
      is a critical public health intervention.

PMID- 17208768
TI  - How to move Canada's workplaces to sustainability.

PMID- 17208767
TI  - Coming to a town near you: corporate globalization and its impact on
      massachusetts workers.
AB  - This report examines five themes of globalization: trade agreements and job loss;
      corporate growth; outsourcing and privatization; downward wage pressures; and
      immigration. We begin with an overview that connects each of these themes to the
      Massachusetts experience and highlights the corporate strategies that are
      affecting this experience. These themes are then interwoven throughout the three
      case studies that follow: "forced supplier migration" at a GE supply plant in
      Wilmington; outsourced dining service workers at Harvard; and the transformation
      of the fish processing industry in New Bedford.

PMID- 17208770
TI  - A global strategy for labor.
AB  - The rules of the global market were established to protect the interests of
      investors at the expense of workers and they shift benefits to investors, costs
      to workers. Globalization is measured by the interests of investors. But 20 years
      of investor protectionism show that growth has slowed and equality has gotten
      worse. The purpose of neo-liberal policies has been to discipline labor to free
      capital from having to bargain with workers over gains from rising productivity.
      But such bargaining is the essence of a democratic market. Uncontrolled
      globalization puts government's domestic policies on the side of capital. In an
      economy whose growth depends on foreign markets, rising domestic wages make it
      harder to compete internationally. There has been a general deterioration of
      labor's position relative to capital's. A global marketplace implies a global
      politics, and the real work happens when representatives of multi-national
      business privately negotiate the rules. Labor must change the framework in which
      the investor class pursues its interest across borders, while workers are
      constricted by borders. Labor unions are critical; they can deny the human
      resource necessary for profits. The strike is the ultimate threat to investors.
      One solution: a "grand bargain" linking development with broadly increased living
      standards connected to planning for sustainable development to create a global
      social contract. Workers have advantages: they are the majority and they are
      indispensable.

PMID- 17208771
TI  - Remembering Ric Pfeffer, celebrating his work.
AB  - This speech was given in a homage celebration to Ric Pfeffer on the occasion of
      his retirement. The article pays tribute to Ric's life and work, showing how his
      commitment to improve the life and working conditions of the population of the
      United States led him to stand up to many powerful forces that determined the
      nature of awards and visibility in this country. The article concludes that it is
      because of people like Ric Pfeffer that the quality of life improves for working
      people, even though the establishment of this country, responsible for most of
      what is wrong, marginalizes and ignores them.

PMID- 17208772
TI  - Work and health in the global economy: lessons from developing and industrialized
      countries on the impact of work on health.
AB  - Occupational and environmental health are dependent on the decisions made about
      the production of goods and services: the quality of our lives in the community
      and workplace and our well-being as workers, residents, and citizens are
      profoundly influenced by the technology employed in producing "our way of life."
      We seek to understand the system of decision making about the use of humans and
      the natural environment in production; we want to know who is sitting at the
      table where decisions are taken and what drives their decisions; and we want to
      know how ordinary people can take their appropriate place at the table, so that
      they can protect their health and well-being. The global economy is not what it
      seems: a mythology has been created about globalization in which the marketplace
      is the only reality and nations and national identity--human agency--play only a
      minor role.

PMID- 17208773
TI  - The occupational and environmental status of Polish industry: a comparative study
      of the private and public sectors.
AB  - During the last decade, Poland has made a successful transition toward democracy
      and market economy. Since the mid-1990s, we have studied the reforms in the
      environmental and occupational protection system in Poland, focusing on the
      privately owned firms. We found that considerable progress has taken place,
      especially in increasing the accountability of private employers and in improved
      enforcement. The fundamental legitimacy of regulators and the regulatory process,
      and the capacity for case-specific decision-making, are among the key explanatory
      factors. The case-specific implementation in Poland is consistent with models
      advocated by several authors in relation to other industrialized European
      economies. We attribute these developments in Poland to the continuity of
      institutions, and the generally good "fit" between the policies and institutions
      on one hand, and their social context on the other, including a wide sharing of
      certain values and norms. The outstanding question from our previous work has
      been the fate of state-owned firms, which may be facing different issues than the
      privatized ones, both in terms of economics, organizational culture, and
      relationships with the regulatory authorities. In this article, we report the
      results of a comparison between the private and state-owned firms, based on the
      questionnaire surveys of the two sectors. We find a striking similarity in
      performance of both sectors and in the authorities' attitudes toward both. These
      findings support our earlier proposition that Poland's success in instituting an
      effective occupational protection system is deeply embedded in the attitudes
      toward protecting workers' health and safety and toward balancing competing
      societal objectives. These attitudes have not changed during the transition to
      the market economy.

PMID- 17208774
TI  - Precaution, prediction, proof, and policy assessment.
AB  - The challenge of sustainable development--the ultimate goal of precaution--
      demands that we shift our focus away from individual environmental problems and
      toward long-term integration of environmental, social, and economic policy. It
      also elevates protection of ecosystem processes and biodiversity to the status of
      significant policy goals. In this article, the author argues for a new use of the
      precautionary principle, as a means to assess broad policy decisions to target
      indirect or systemic rather than direct threats to sustainability. He draws on a
      case study of two Australian policies: the National Strategy for Ecologically
      Sustainable Development (ESD), and the National Competition Policy (NCP).1 While
      the proposals are ambitious and may not be achievable in the near future,
      nonetheless, it is in the nature of institutional and policy systems that it is
      difficult to predict when opportunities for policy change will arise. It is
      crucial to develop and articulate strategies now, to be promoted during brief
      windows of opportunity for policy change.

PMID- 17208775
TI  - Selling before telling: why the government needs to take a second look at
      genetically engineered foods.
AB  - This article documents the early warning signs of health and environmental
      dangers of DDT, vinyl chloride, and leaded gasoline. In each case, industry
      scientists and/or public health officials warned of potential hazards but their
      advice was ignored at great cost to human health and the environment. Now,
      genetically engineered (GE) foods have been introduced to our food supply and
      exhibit many of the same early warning signs. Leaded gasoline was sold in the
      United States from 1923 through 1986. The additive was introduced without safety
      testing even though it was known that lead was neurotoxic. Industry efforts kept
      the federal government from studying or banning leaded gasoline for decades.
      Leaded gasoline released millions of tons of lead into the air. Lead can cause
      brain damage and even death. Vinyl chloride, used to make PVC plastic, has a
      similar history. When scientific studies confirmed that vinyl chloride was a
      carcinogen, industry representatives signed a secrecy agreement to keep the
      information from becoming public. DDT was used all over the United States to kill
      unwanted pests. Evidence of DDT's environmental and health impacts began to
      emerge in the 1950s. DDT is now deemed a probable human carcinogen, suspected of
      causing liver damage, and blamed for triggering premature births. GE foods have
      been introduced into our food supply with no required safety testing. Initial
      independent studies indicate that GE foods can trigger unexpected or unknown
      allergic reactions, may damage organs and immune system, can contaminate
      neighboring crops, and may cause ecological damage. Yet, industry studies about
      GE food products are considered proprietary and are not available for peer review
      or public scrutiny. In reaction to the rejection of GE foods by many European
      countries and companies, the biotechnology industry is waging a massive
      propaganda effort in the United States. But when it comes to our food supply, we
      should not take any health or safety risks. We make these recommendations: *Hold
      biotechnology companies liable for any harm that comes from the use of GE foods.
      This will give them a financial incentive to ensure that GE foods are safe and
      provide compensation to any future victims. *Place a moratorium on GE foods until
      they are proven safe through independent, long-term testing for health and
      environmental impacts. *Require labeling of all GE foods that are proven safe to
      give consumers the right to know and choose.

PMID- 17208776
TI  - Comment and controversies: since "Silent Spring": new voices, new analyses, and
      new movements.
AB  - Forty years ago, in the enormously praised and fiercely criticized book, "Silent
      Spring", Rachel Carson demonstrated the dangers of pesticides to humans and
      ecosystems and called for precaution in their use. Yet, the majority of
      environmental regulations passed since 1962 have primarily addressed pollutant
      discharge rather than cleaner products and technologies. The number of active
      ingredients in pesticides used in the United States has risen from 32 in 1939 to
      860 in recent times, while the overall volume of agrochemicals applied has nearly
      doubled since the publication of Silent Spring. The last 40 years have brought
      significant changes with respect to environmental policies, agricultural
      technologies, urbanization, civil rights, women's rights, the roles of non-profit
      organizations and community development, and increased poverty, hunger, and
      economic inequality. In recent years, new voices, new analyses, and new movements
      have emerged offering fresh perspectives on how we can answer Carson's clarion
      call to protect our planet and ourselves.

PMID- 17208777
TI  - Occupational health morality and economy interact.

PMID- 17208779
TI  - Sewers, sewage treatment, sludge: damage without end.
AB  - It is in the nature of sewering and sewage treatment to compound environmental
      problems in the process of moving sewage and in attempting to remove from sewage
      the pollutants it carries. Spreading sewage sludge on land is but the latest in
      the compounding of environmental damage from sewerage. This practice must be
      banned and there must be a federal reorientation of all technology dealing with
      human excreta and the waste materials from industry and society that now are
      carried away by sewers. The reorientation must center on biologically based on
      site pollution prevention and resource recycling technologies mandated through a
      revised Clean Water Act.

PMID- 17208780
TI  - Sludge, biosolids, and the propaganda model of communication.
AB  - The Water Environment Federation's elaborate effort to rename sewage sludge as
      "biosolids" is an example in practice of the "propaganda model" of
      communications, which sees its task as indoctrinating target audiences with ideas
      favorable to the interests of the communicators. The propaganda model assumes
      that members of the public are irrational and focuses therefore on symbolic and
      emotional aspects of communication. This approach to communicating arouses public
      resentment rather than trust. In place of a "propaganda model," public officials
      should adopt a "democratic model," which assumes that audiences are rational and
      intellectually capable of meaningful participation in decision-making.

PMID- 17208781
TI  - Sewage sludge--looking upstream: the precautionary principle.
AB  - The health care industry makes a unique contribution to the potential public
      health and environmental impacts of sewage sludge production and disposal. As
      materials flow into and out of health care facilities, potentially hazardous
      substances, like mercury, solvents, and pharmaceutical compounds, are introduced
      into the waste stream and ultimately into sewage sludge. Although the hazards
      posed by these practices are often not fully understood or the risks quantified,
      concern about impacts on public health and the environment is fully justified.
      How to deal with the uncertainties surrounding the impacts of these practices
      becomes an ethical as well as a scientific question. A precautionary approach to
      materials manufacture, use, and disposal encourages us to look upstream and to re
      design products and systems in ways that primarily prevent problems rather than
      dealing with them at the "end of the pipe." Early warning systems, shifting the
      burden of proof, alternatives assessment, and monitoring programs are suggested
      as interventions that might be used as part of a precautionary approach to
      addressing the generation and disposal of sewage in an industrial society.

PMID- 17208782
TI  - The role of citizen activism in protecting public health and the environment from
      land application of sewage sludge: an interview with EPA's Hugh B. Kaufman.
AB  - This article--an account of an interview with an Environmental Protection Agency
      (EPA) official--addresses the role of citizen activism in combating environmental
      decisions that may cause harm, including the sludge policy of the EPA.

PMID- 17208783
TI  - Sludge victims: voices from the field.
AB  - Individuals around the country are filing reports of adverse health effects they
      say are related to exposures to sludge. This article reviews some of those
      reports as well as officials' reactions and responses to them.

PMID- 17208784
TI  - Have risks associated with the presence of synthetic organic contaminants in land
      applied sewage sludges been adequately assessed?
AB  - Land application has become the dominant means for sewage sludge disposal in the
      United States. In 1993, the EPA concluded that synthetic organics therein posed
      an insignificant risk, based on the results of the 1988 National Sewage Sludge
      Survey, the view that most persistent organics are no longer in commerce and that
      industrial pretreatment further reduces their release to municipal treatment
      plants. However, we detected high concentrations of several problematic compounds
      in biosolids that were overlooked in the risk assessment, including persistent,
      bioaccumulative polybrominated diphenyl ethers and estrogenic nonylphenols. These
      results and other findings call into question the assessment's certainty.

PMID- 17208785
TI  - Investigation of alleged health incidents associated with land application of
      sewage sludges.
AB  - The majority of U.S. sewage sludges are disposed by application to land for use
      as a soil amendment. Class B sludges, containing a complex mix of chemical and
      biological contaminants, comprise the majority. Residents near land application
      sites report illness. Symptoms of more than 328 people involved in 39 incidents
      in 15 states are described. Investigation and tracking of the incidents by
      agencies is poor. Only one of 10 EPA regions provided substantial information on
      the incidents in their region. Investigations, when conducted, focused on
      compliance with regulations. No substantial health-related investigations were
      conducted by federal, state, or local officials. A system for tracking and
      investigation is needed. Analysis of the limited data suggests that surface
      applied Class B sludges present the greatest risk and should be eliminated.
      However, even under less risky application scenarios, the potential for off-site
      movement of chemicals, pathogens, and biological agents suggests that their use
      should be eliminated.

PMID- 17208786
TI  - Interactions of pathogens and irritant chemicals in land-applied sewage sludges
      (biosolids).
AB  - Fertilization of land with processed sewage sludges, which often contain low
      levels of pathogens, endotoxins, and trace amounts of industrial and household
      chemicals, has become common practice in Western Europe, the United States, and
      Canada. Local governments, however, are increasingly restricting or banning the
      practice in response to residents reporting adverse health effects. These self
      reported illnesses have not been studied and methods for assessing exposures of
      residential communities to contaminants from processed sewage sludges need to be
      developed. METHODS: To describe and document adverse effects reported by
      residents, 48 individuals at ten sites in the United States and Canada were
      questioned about their environmental exposures and symptoms. Information was
      obtained on five additional cases where an outbreak of staphylococcal infections
      occurred near a land application site in Robesonia, Pennsylvania. Medical records
      were reviewed in cases involving hospitalization or other medical treatment.
      Since most complaints were associated with airborne contaminants, an air
      dispersion model was used as a means for potentially ruling out exposure to
      sludge as the cause of adverse effects. RESULTS: Affected residents lived within
      approximately 1 km of land-application sites and generally complained of
      irritation (e.g., skin rashes and burning of the eyes, throat, and lungs) after
      exposure to winds blowing from treated fields. A prevalence of Staphylococcus
      aureus infections of the skin and respiratory tract was found. Approximately one
      in four of 54 individuals were infected, including two mortalities (septicemia,
      pneumonia). This result was consistent with the prevalence of S. aureus
      infections accompanying diaper rashes in which the organism, which is
      occasionally found in the lower human colon, tends to invade irritated or
      inflamed tissue. CONCLUSIONS: When assessing public health risks from applying
      sewage sludges in residential areas, potential interactions of chemical
      contaminants with low levels of pathogens should be considered. An increased risk
      of infection may occur when allergic and non-allergic reactions to endotoxins and
      other chemical components irritate skin and mucous membranes and thereby
      compromise normal barriers to infection.

PMID- 17208787
TI  - Primary prevention of chemical contamination.
AB  - The current approach to addressing health and ecosystem risks from biosolids, or
      sludge, requires identification of so-called "safe" or "acceptable" levels of
      exposure and installation of controls to achieve such levels. This end-of-the
      pipe approach is inconsistent with the public health concept of primary
      prevention. Following an overview of the limitations in current approaches to
      understand and address risks of biosolids contamination, we present a new,
      preventative paradigm for addressing the hazards of sludge. We conclude that
      given the disparate and widely distributed sources of contaminants in biosolids
      and the amount of uncertainty in information about health and environmental
      effects, we need a new approach to this and other environmental dilemmas. This
      approach is embodied in the concept of the precautionary principle and public
      health goal-setting.

PMID- 17208788
TI  - ER training: issue of consensus in minimum criteria for HAZWOPER training.

PMID- 17208789
TI  - Introduction: The science and politics of radiation studies.

PMID- 17208790
TI  - The relevance of occupational epidemiology to radiation protection standards.
AB  - Large-scale epidemiological studies of U.S. Department of Energy workers have
      been underway since the 1960s. Despite the increasing availability of information
      about long-term follow-up of badge-monitored nuclear workers, standard-setting
      bodies continue to rely on the Life Span Study (LSS) of A-bomb survivors as the
      primary epidemiological basis for making judgments about hazards of low-level
      radiation. Additionally, faith in the internal and external validity of studies
      of A-bomb survivors has influenced decisions about the design, analysis, and
      interpretation of many worker studies. A systematic comparison of the LSS and
      worker studies in terms of population characteristics, types of radiation
      exposures, selection factors, and dosimetry errors suggests that the priority
      given to dose response findings from the LSS is no longer warranted. Evidence
      from worker studies suggests that excess radiation-related cancer deaths occur at
      doses below the current occupational limits; low-dose effects have also been seen
      in studies of childhood cancers in relation to fetal irradiation. These findings
      should be considered in revising current radiation protection standards.

PMID- 17208791
TI  - The health risks of decommissioning nuclear facilities.
AB  - The health risks facing workers involved in decommissioning nuclear facilities
      are a critical concern as the nuclear weapons complex and nuclear power plants
      begin to be dismantled. In addition to risks from exposure to radioactive
      materials, there are risks from other common industrial materials like
      crystalline silica dust and asbestos. We discuss these issues in the context of
      recent research on the risk of low-level ionizing radiation, the classification
      of crystalline silica as a carcinogen, and early experience with decommissioning
      nuclear facilities in the United States. Health and safety advocates will need to
      be vigilant to prevent worker exposure.

PMID- 17208792
TI  - Observational studies as human experimentation: the uranium mining experience in
      the Navajo Nation (1947-66).
AB  - This article evaluates how an observational epidemiologic study of federal
      agencies in uranium miners became an experiment of opportunity for radiation
      effects. Navajo miners and communities suffered environmental exposures caused by
      the practices of uranium mining and milling in the Navajo reservation during the
      1947 to 1966 period. A historical review of the state-of-the-art knowledge of the
      health effects of uranium mining and milling during the years prior to 1947 was
      conducted. Contemporary prevention and remediation practices also were assessed.
      An appraisal of the summary of findings of a comprehensive evaluation of
      radiation human experimentation conducted by the U.S. federal government in 1995
      96 (ACHRE) demonstrates that uranium miners, including Navajo miners, were the
      single group that was put more seriously at risk of harm from radiation
      exposures, with inadequate disclosure and often with fatal consequences. Uranium
      miners were unwilling and unaware victims of human experimentation to evaluate
      the health effects of radiation. The failure of the State and U.S. Governments to
      issue regulations or demand installation of known mine-dust exposure control
      measures caused widespread environmental damage in the Navajo Nation.

PMID- 17208793
TI  - Women uranium workers: a case study of perceived hazardous exposures and health
      effects.
AB  - An exploratory study of seventy-four women uranium workers employed in the
      western United States (miners, millers, truck haulers, and office workers) was
      conducted. These uranium industry workers were employed primarily during the
      1970s and 1980s. It was found that approximately 60 percent perceived overall
      moderate to high levels of dust during their employment, and about 50 percent
      reported the likelihood of having past, present, or future health problems
      related to their uranium work. Two of the most-often-identified health problems
      were respiratory symptoms or illnesses and cancer. Issues regarding public
      policy, research, and worker rights are discussed.

PMID- 17208794
TI  - Into the nuclear age as a hand mucker: interview with Navajo George Tutt, former
      uranium miner. Interview by Timothy Benally.

PMID- 17208795
TI  - Caution! NRC as protector of worker health and safety at nuclear power plants.
AB  - Congress may soon face a decision about what agency will take responsibility for
      worker and facility safety at Department of Energy (DOE) sites as the DOE moves
      to external regulation. The Nuclear Regulatory Commission (NRC) occupies a
      prominent place on the short list of candidates. Thus, an examination of the
      NRC's historical record on health and safety, in particular, its record in
      protecting workers, is warranted. This look at the record shows that the NRC does
      not adopt a strong regulatory stance; exposure standards for workers have not
      changed despite evidence of harmful effects at low doses of radiation exposure;
      record-keeping and worker monitoring are lax; the NRC is blind to internal
      cultural problems; it appears more concerned about its public image than about
      entrenched problems; it is too lenient to the industry it is supposed to
      regulate. The NRC's history of recent problems has caused some critics to call
      for Congressional hearings or additional oversight of the agency.

PMID- 17208796
TI  - Global flexibility--shop floor flexibility: what's a worker to do?
AB  - For several years new forms of work organization have been introduced by U.S.
      management to cut labor costs, improve productivity, and increase their shop
      floor control. Corporations have also invested in computer-controlled machinery
      in an effort to eliminate large numbers of skilled blue-collar workers and to
      decrease their reliance on the tacit knowledge of such workers. Once seemingly
      secure jobs in diverse industries like airplanes, jet engines, machine tools, and
      computer chips, are no longer so stable. In an effort to expand their global
      reach and reorganize the workplace, managers are able to capitalize on two
      conflicted and conflicting attitudes among the workforce: the first, workers most
      deep-seated fear, the loss of a permanent job; the second, their aspirations to
      contribute their knowledge and skills in a positive way on the shop floor. In
      this article the reorganization of work at two western Massachusetts metalworking
      companies is described. What distinguishes these cases is the central role that
      the union played in the organized plant and the workers played in both plants to
      improve production and at least for now preserve jobs.

PMID- 17208797
TI  - Clear and complete presentation of air sampling data.
AB  - One important area in which change and improvement is needed in industrial
      hygiene practice is in the presentation of air sampling data. Many types of
      people rely on such industrial hygiene data when dealing with chemical exposures.
      Yet there is presently no standard of good practice among industrial hygienists
      and data is now presented in many different formats. Tables of data, many of
      which invite misinterpretation, are common. Adoption of the suggested report
      elements and tabular format presented here will help to establish a standard of
      good practice in the presentation of industrial hygiene sampling data.

PMID- 17208798
TI  - Petition to the Massachusetts Toxics Use Reduction Institute to list crystalline
      silica on its hazards list.

PMID- 17208801
TI  - Lead suit: an immodest proposal.
AB  - Rhode Island's Attorney General Whitehorse has announced that Rhode Island will
      sue the lead paint industry for its contribution to the epidemic of health
      problems caused by lead paint. The suit asserts that the paint industry was
      negligent because it marketed a harmful product; since it caused the problem, it
      should contribute to paying for it. We need a lead trust fund to provide for
      primary abatement upkeep and maintenance of housing. The attorney general's
      action can, if successful, help implement such a fund. Personal lead injury
      cases, which have a minimal public health impact, can be channeled to do so.
      Whenever personal injury cases are settled--either through negotiated settlement
      or full jurisprudence--a percentage of the settlement could be earmarked for a
      public lead trust fund.

PMID- 17208802
TI  - Why promote campaigns for clean products and clean production?
AB  - Environmental advocacy in the United States has focused on controlling pollution
      and waste through a system based on government permits for managing the release
      of environmental pollutants. The conventional focus on pollution control and
      waste management has been less than comprehensive. From an ecological perspective
      it makes little sense to focus on reducing environmental pollution from the waste
      pipe of industrial facilities while ignoring those same pollutants when inside
      the plant or sent out the product door. But an ecological perspective is not the
      same as a political perspective. The focus on pollution and waste has achieved
      legitimacy; focusing on production appears to invite an invasion of private
      property, a sensitive issue for most businesses. Discussing the constituents and
      volume of products treads on issues many think should best be reserved for the
      market. Focusing on production and products requires technical knowledge and
      skills not conventionally found in environmental advocacy organizations. Why
      should environmental or occupational health advocates stretch their conventional
      domain? Here is an argument for products and production, listing ten reasons for
      campaigning on clean production and products.

PMID- 17208803
TI  - Trade unions and cleaner production: perspectives and proposals for action.
AB  - Despite their reputation for linking progress and security to dirty smokestacks,
      many trade unions around the world have designed and fought for sophisticated
      environmental policies--many of which promote a radical restructuring of
      production in order to prevent environmental harm. This article surveys trade
      union perspectives on cleaner production and offers examples of trade union
      action for cleaner production in the United States and around the world. Two
      general conceptual frameworks arising out of union writing on the subject--the
      "Transition Position" and the European-based "Harmony of Interests"--are
      elaborated. The article concludes with recommendations for employee participation
      in pollution prevention activities and ideas for a trade union agenda on cleaner
      production.

PMID- 17208804
TI  - Documenting the asbestos story in Sarnia.
AB  - An occupational health and safety clinic in Windsor, Ontario, expressed its
      concerns about the health of former workers at a foundry and insulation plant in
      Sarnia to the Canadian Auto Workers union early in 1998. The workers suffered
      cancer, respiratory and hearing problems, and heart disease. An investigation of
      their workplace exposures ensued. Researchers obtained government documents that
      showed the history of ineffectual regulation at Sarnia and some of the highest
      levels of asbestos--hundreds of times over the legal limits--ever recorded in
      Canadian workplaces.

PMID- 17208805
TI  - Prevention and transition.
AB  - Strategies to protect workers' health and the environment outside of the
      workplace, were, respectively, once based on the notion of control a series of
      controls (engineering and administrative) in the workplace and emission controls
      to protect the public environment. Two parallel changes occurred. The first was a
      shift from the general principles of control to the notion of a hierarchy of
      control measures and the second was a recasting of the Hierarchy of Controls into
      what has been called a Hierarchy of Prevention and Controls. This article cites
      the Canadian experience to show that this twofold shift is a progressive and
      constructive move; the United States provides both the sources of the problem and
      some solutions. "Just Transition" for workers during environmental change was
      developed in the context of chemical bans and phase-outs. The concept is now much
      broader. The article argues that certain pollution prevention measures have been
      construed as an attack on workers' rights; but this problem can be resolved to
      the benefit of both workers' health and environmental protection. Explanation of
      the relation of pollution prevention to Just Transition is a part of the
      solution.

PMID- 17208806
TI  - Lawsuit challenges U.S. on NAFTA.

PMID- 17208807
TI  - Strengthening occupational and environmental health and safety protections in a
      global economy.

PMID- 17208810
TI  - Linking work organization and policy: an invitation.

PMID- 17208811
TI  - 'Gold standard' for remediation of WTC contamination.
AB  - The events of September 11, 2001 and thereafter resulted in arguably the worst
      environmental disaster in the history of New York City. Particulate matter and
      combustion by-products containing asbestos, lead, mercury, dioxin, PAHs, and
      other toxic substances, not only affected rescue and recovery workers but also
      infiltrated thousands of residences and workplaces. Government agencies did not
      acknowledge responsibility for residential indoor environmental quality until
      eight months later, and still have not accepted responsibility for indoor
      environmental quality in commercial or government buildings. In May 2002, 200
      representatives from 38 community, labor, environmental, and public health
      organizations met to discuss unmet post-9/11 public health needs. They
      established a technical working group to press the Environmental Protection
      Agency to expand and improve its proposals for the cleanup of Lower Manhattan.
      This 2002 document, "The 'Gold Standard' for Remediation of WTC Contamination,"
      articulates the environmental health concerns and suggestions of grassroots
      organizations active in 9/11 response efforts at that time.

PMID- 17208812
TI  - Independent of what? The independent medical examination business.
AB  - Workers suffering from a work-related health condition frequently are required to
      undergo examination by a physician chosen by the employer or a Workers'
      Compensation Insurance Carrier. While the opinions of physicians performing these
      "Independent Medical Examinations" (IMEs) have been criticized as biased by a
      conflict of interest, IME advocates assert that the methods used by the IME
      result in an objective and superior opinion. This article explores this claim to
      objectivity and superiority. It argues that pro-employer/carrier bias is embedded
      in the methodology IMEs advocate, and that the practical impact of the IME
      approach is to reduce the recognition of occupationally related health conditions
      and to minimize the disability associated with such conditions. The IME approach
      is more accurately characterized as a tool to standardize a product that can be
      marketed to corporate clients, rather than a way to precisely assess work-related
      health conditions.

PMID- 17208814
TI  - Fairy tale mine.

PMID- 17208813
TI  - Day labor and occupational health: time to take a closer look.
AB  - The term "day labor" refers to work performed by individuals who are hired on a
      temporary basis, often for one day at a time. This type of employment has
      increased in North America as informal work arrangements and immigration have
      increased. Research on the occupational health of day laborers is minimal. The
      objectives of this article are to review the current literature pertaining to
      occupational health in day laborers, and to characterize the issues that affect
      this population's access to occupational health services. Surveys of day laborers
      and other immigrant, low-wage workers show that they are at elevated risk for
      occupational injury and are often unable to access medical care when injured on
      the job. Reasons include workers' reluctance to complain about unsafe work
      conditions, inadequate safety training, and lack of incentive for employers to
      reduce workplace injuries. More research is needed to better characterize the
      occupational health of this population.

PMID- 17208815
TI  - We are the keepers of the environment: an interview with Stephen L. Gauthier,
      health and safety activist, member of IUE/CWA local 201.

PMID- 17208816
TI  - Pete Grimwood--oil cargo seafaring and longshoring.

PMID- 17208817
TI  - Draft Public Health Statement on the U.S.-Central American Free Trade Agreement
      (CAFTA).
AB  - The U.S. is rapidly negotiating a raft of new regional and bilateral trade
      agreements. The most recent agreement, with Central America, [was to] come before
      Congress for a vote as soon as late May. There is growing concern that
      international trade agreements threaten health care and the health of
      communities. . . . The Draft Public Health Statement on the U.S.-Central American
      Free Trade Agreement (CAFTA), developed by CPATH which planned a campaign around
      the issues, analyzes key provisions from the perspective of public health and
      suggests reframing the trade debate in terms of health.

PMID- 17208819
TI  - New points of production: homework and shoemaking in Asia.
AB  - Globalization--and the manner in which it has been governed during the last
      decade--has harmed various public policy infrastructures of developing nations,
      but especially those in health, social, and environmental sectors. The poorest
      population suffers the most severe consequences, as production takes place in the
      "informal" economy and in homes. Work safety and health in the informal economy
      has not gained the attention it warrants and requires, considering that this
      "sector" constitutes the majority of the world's labor force. The purpose of this
      article is twofold: (i) to describe the working environment in home-based
      shoemaking--based on Indonesian and Philippines experience by Markkanen [1]; and
      (ii) to examine the research framework proposed by Levenstein and Tuminaro in The
      Political Economy of Occupational Disease [2] and further developed in Wooding
      and Levenstein, The Point of Production, 1999 [3]. The field investigation by
      Markkanen employed this approach to explore how hazardous working conditions and
      inadequate health protection are the product of complex, converging relationships
      among diverse "actors" or agents at international, national, community, and shoe
      industry levels.

PMID- 17208820
TI  - Occupational health among Latino workers: a needs assessment and recommended
      interventions.
AB  - Evidence suggests that Latino workers, along with other minority and low-income
      workers, face a higher risk for occupational disease than do other workers.
      Targeted surveillance and primary prevention interventions have been lacking or
      inadequate. The authors estimate the number of occupational disease deaths and
      new cases in Latino workers in the United States. Then, using data from New York
      City, they find that Latino workers are disproportionately employed in more
      hazardous occupations and underrepresented in less hazardous jobs. They suggest a
      comprehensive approach to address workplace disease in Latino workers, which
      involves primary prevention interventions, clinical services, educational
      approaches, research and surveillance, unionization and organization of workers,
      and legislation and regulation.

PMID- 17208821
TI  - Integrating smoking cessation into worker training among Latino immigrant
      workers: development of a program.
AB  - The prevalence of smoking among Latino immigrant workers needs to be addressed
      with culturally and linguistically appropriate smoking cessation programs. One
      innovative approach to reaching these workers is through worker health and safety
      training programs. These programs offer multiple opportunities to provide smoking
      cessation messages, a "teachable moment" to focus on health issues, and the
      likelihood that peers and family members will share these messages. A
      collaborative effort between an occupational health and safety training facility
      and a university utilizing Latino and non-Latino personnel developed a smoking
      cessation program integrated with worker health and safety training. Preliminary
      results of an evaluation of the program indicate that the program was able to
      reach a wide range of immigrant workers and improve their knowledge of the risks
      of smoking and the effectiveness of different methods of quitting smoking.

PMID- 17208822
TI  - A national assessment of the status of planning for public health preparedness
      for chemical and radiological contaminating terrorism: CSTE'S findings and
      recommendations/executive summary.
AB  - An association of epidemiologists looks at the state of regional public health
      preparedness in a time of terrorism in a report that gauges regional readiness.
      The report examined the status of preparations to deal with chemical and
      radiological events, and looked at planning gaps, resources, and interagency
      agreements to coordinate emergency response. The research found inadequate levels
      of preparedness, planning, and established interagency partnerships and puts
      forth recommendations to improve the nation's ability to respond.

PMID- 17208823
TI  - Technical assistance to the grassroots, part I: an issue of framing?

PMID- 17208824
TI  - Technical assistance to the grassroots, part ii: erin brockovich revisited--a
      lesson for social policy-making and agency.
AB  - Reading "Technical assistance: Providing grassroots groups access to scientific
      and technical information" by Barbara Berney (New Solutions, Vol. 15, No. 1), I
      was overtaken by a subliminal image of Erin Brockovich (looking like Julia
      Roberts), who was a self-taught technical assistance provider (TA). For
      progressives, radicals, for those who apply participatory methods in research,
      for those familiar with the work of Paolo Freire and the benefits of building
      critical consciousness, there are some interesting extensions that can be drawn
      from the success stories of TAs working with grassroots groups.

PMID- 17208825
TI  - Dangers, delights, and destiny on the sea: fishers along the East coast of north
      sumatra, indonesia.
AB  - This article describes a collaborative project between the International Labour
      Organization's International Programme on the Elimination of Child Labour (IPEC)
      and the Lowell Center for Sustainable Production, in identifying work hazards of
      fishers along the east coast of North Sumatra, Indonesia, in July 2004. The study
      employed qualitative investigation techniques: participant observations at
      fishing villages and harbors; and interviews with local fishers and skippers.
      Fishers work long hours in life-threatening conditions, often with low pay. It
      would be synergistic to incorporate fishing safety and health policies and
      advocacy efforts into reconstruction undertakings of fisheries devastated by the
      2004 tsunami.

PMID- 17208826
TI  - Labor and the tobacco institute's labor management committee in new york state:
      the rise and fall of a political coalition.
AB  - In 1984 the Tobacco Institute and the Bakery, Confectionary and Tobacco Workers
      Union formed a Labor Management Committee. From the mid-1980s to the mid-1990s,
      this LMC worked to elicit labor support in New York by framing issues in terms
      that made them salient to unions: tobacco excise taxes as regressive taxation,
      workplace smoking restrictions as an intrusion into collective bargaining. By the
      late 1990s, however, most of labor in New York had shifted to support for anti
      tobacco policies. The reasons for this shift include the growing size and
      influence of public-sector unions, and their generally favorable stances on
      tobacco control issues; the policy-making autonomy of the unions; the growing
      body of scientific knowledge concerning the dangers of tobacco use; and the rise
      in public awareness of such dangers. Nevertheless, for two decades, the LMC
      contributed to mutual suspicion between labor and tobacco control advocates that
      prevented collaboration between them.

PMID- 17208827
TI  - Why nafta failed and what's needed to protect workers' health and safety in
      international trade treaties.
AB  - Labor standards, including occupational health and safety regulations and
      enforcement, are being subjected to intense downward pressures as a result of
      fundamental shifts in the global economy. The 1994 North American Free Trade
      Agreement (NAFTA) was the first trade treaty that attempted to promote and
      protect workplace health and safety through a "labor side agreement." NAFTA
      failed to protect workers' health and safety due to the weaknesses of the side
      agreement's text; the political and diplomatic considerations limiting its
      implementation; and the failure to recognize and address the economic context,
      and political consequences of this context, in which the agreement was
      implemented. Subsequent trade treaties, both bilateral and regional, have not
      overcome the weaknesses of NAFTA. The treaty components needed to protect
      workers' health in future trade agreements are: 1) a minimum floor of
      occupational health and safety regulations; 2) an "upward harmonization" of
      regulatory standards and actual practice; 3) inclusion of employers so that they
      have formal responsibility and liability for violations of the standards; 4)
      effective enforcement of national regulations and international standards; 5)
      transparency and public participation; and 6) recognition of disparate economic
      conditions among trading partners and provision of financial and technical
      assistance to overcome economic disincentives and lack of resources. Also
      required are continued actions by non-governmental actors, including the workers
      themselves and civil society organizations.

PMID- 17208829
TI  - RAISING THEIR VOICES FOR THE RECORD: Testimony of Philadelphia Area Project on
      OSH at a Congressional Forum--A Job to Die For--About Inadequate Enforcement of
      U.S. Safety Standards, May 12, 2004.

PMID- 17208828
TI  - Occupational safety and health in china, part I: u.s.-China symposium on
      "integrating occupational and environmental health".
AB  - A joint China-U.S. symposium entitled "Integrating Occupational and Environmental
      Health" was organized by the Department of Science and Technology of Hebei
      Province, PRC, and the Department of Work Environment at the University of
      Massachusetts Lowell, U.S.A. A framework called "Sustainable Production" was
      proposed by U.S. participants to link environmental and worker protection.
      Sustainable production focuses on systems of production that integrate concerns
      for the long-term viability of the environment, worker health and safety, the
      community, and the economic performance of firms and other enterprises. The
      disciplines of environmental and occupational health and safety were brought
      together by Chinese participants under the unifying theme of the development,
      implementation, and impact of new technologies. As production processes are
      increasingly concentrated in China, collaboration among U.S. and Chinese
      environmental and occupational health and safety professionals is ever more
      essential.

PMID- 17208830
TI  - Editorial: in-house changes.

PMID- 17208831
TI  - Are separate standards for occupational and environmental exposures good public
      health policy?
AB  - Occupational and environmental exposures are treated as distinct entities for the
      purpose of public health protection. Yet workers and community members may
      experience the same exposures simultaneously or within a very narrow time frame.
      Agricultural chemicals applied by workers in the field drift into residential
      communities. Chemicals may be carried from a work site, with or without physical
      boundaries, into the home and delivered to household members. Meteorological
      conditions transport agricultural chemicals or stored ashes to residential
      communities during and after the work day. Occupational standards generally allow
      a higher level of exposure to workers than environmental standards allow for
      community exposures. For some chemicals, standards exist for only one exposure
      group, thus leaving the other exposed group without protection. The distinction
      between occupational and environmental exposures assumes the identification of
      specific human activities as work or non-work. However, not all human activity
      falls clearly into one specific category. The strict separation of occupational
      and environmental exposures therefore renders public health protection of all
      exposed people difficult to achieve. An in-depth discussion about the factors and
      assumptions that are used when occupational and environmental standards are
      separately applied to exposed populations is needed to enhance the public health
      of all people.

PMID- 17208832
TI  - Working at the check-in: consequences for health.
AB  - No body of literature exists related specifically to the occupational health of
      airport check-in workers. The problems encountered by airport check-in workers
      are typical of other service-sector occupations with similar work-related health
      hazards, particularly those characterized by a high level of demand with low
      worker control, performed predominantly by women. The knowledge gap could be
      narrowed by broadening the scope in both traditional occupational health and
      ergonomics studies to take into equal consideration jobs performed by women. In
      an attempt to reduce the knowledge gap specific to airport check-in workers,
      literature was reviewed on several other worker populations whose job
      characteristics include elements similar to airport check-in work: computer
      clerical workers, supermarket check-in workers, and airport baggage handlers.
      This cross-population review identified the major elements that have been studied
      in the comparison groups, compared with the factors examined in a study of check
      in workers. The review demonstrates that jobs that may appear completely
      different from the outside, might, upon closer examination, have numerous common
      exposures from a variety of sources. Thus, knowledge about one job may be useful
      for another that has not been investigated. The literature review reveals that it
      would be useful to extend to airport check-in workers recommendations from
      studies of the three comparison populations.

PMID- 17208833
TI  - Qualitative research using numbers: an approach developed in france and used to
      transform work in north america.
AB  - Qualitative research is often opposed to quantitative research. But numbers can
      play an important role in illustrating analyses in qualitative research. Their
      persuasive, concrete nature can help ensure the success of a workplace
      intervention, especially in the North American context, where numbers are treated
      very seriously. We describe a method of work analysis and transformation
      developed at the Conservatoire national des arts et metiers in Paris, where the
      meaning of the numbers used is critical. We think that the numbers used in work
      analysis have a different meaning from that in a "pure" quantitative study, where
      they are submitted to statistical procedures for hypothesis testing. Using
      examples from recent studies carried out in Quebec and Canada in collaboration
      with unions or joint health and safety committees, we show that counting can be
      part of qualitative analysis, enrich our portrait of organizational and physical
      aspects of the work process, and help indicate pathways for workplace
      improvement.

PMID- 17208834
TI  - Show me the money: cost-benefit analysis in the work environment.
AB  - During the last several decades, Cost-Benefit Analysis (CBA) has become a widely
      used technique in public policy-making. This review examines CBA from
      perspectives of both advocates and critics; it looks at its theory and practice,
      its purported advantages and shortcomings in application. It also proposes
      several ways in which the process can be made more accountable.

PMID- 17208835
TI  - IBM EMPLOYEES v. IBM: PITFALLS AND OPPORTUNITIES OF LITIGATION-GENERATED
      RESEARCH.

PMID- 17208837
TI  - Nanoscience and literature: bridging the two cultures.
AB  - The growth of nanoscience and nanotechnology as academic pursuits raises
      important questions about the nature of disciplinarity both within and beyond the
      sciences. These burgeoning fields also offer many opportunities for
      interdisciplinary and multidisciplinary collaboration among the sciences and
      various humanities fields. Literature-nanoscience collaborations, specifically,
      offer one way for workers in the humanities and sciences--the "two cultures"
      described by English scientist-writer C. P. Snow in the late 1950s--to cross the
      great divide that typically isolates them in order more fully to understand and
      address the potential social and moral consequences of developments in
      nanotechnology.

PMID- 17208838
TI  - The stranded standard: what happened to the proposed ilo convention on work in
      the fishing sector?
AB  - The 2005 International Labour Conference did not adopt the new proposed
      Convention on work in the fishing sector. As the whole Employers' Group and a
      considerable number of government delegates abstained from voting, the quorum was
      not reached. Workers are disappointed as the Convention aimed at covering more
      than 90% of the world's fish workers, both in the fields of social security and
      work environment. Employers described the proposed Convention as prescriptive,
      inflexible, and impractical for developing countries to ratify it. How much did
      the Tsunami 2004 influence the result? What kind of standard creation process
      would suit for the new, globalized world?

PMID- 17208839
TI  - Gender and cleaner production: toward a framework for including gender analysis
      when developing strategies and designing solutions.
AB  - Environmental policies that do not consider global gender dimensions often create
      benefits for some people and ecosystems but result in costs for others, in
      particular women, at some point along the global chain of production and
      consumption. This article is intended to begin a dialogue about the importance of
      including gender analysis in the design of cleaner production strategies. We
      review global development policy and its critiques that have identified a need
      for gender awareness and analysis. This examination provides a backdrop for a
      discussion of how to include gender analysis in cleaner production planning and
      implementation. We invite researchers and practitioners to enter this dialogue to
      further the field and develop effective tools and policies to analyze gender
      dynamics, support gender equity, and find environmentally sound solutions that
      are sustainable for the long-term.

PMID- 17208840
TI  - Using qualitative methods to evaluate and make change in the work environment.
AB  - The work environment is a particularly fertile field for the use of qualitative
      research methods such as in-depth interviews and open-ended surveys. These
      methods are well suited to the task of unearthing complex authentic perspectives
      that in the work environment context are so often influenced by social and
      political forces. The results of such methods can be especially powerful in
      enhancing our understanding of why change to better protect workers' health and
      safety does or does not happen and to persuade policy makers of the importance of
      positive change.

PMID- 17208841
TI  - Solving tangled cases of work-related musculoskeletal disorders by international
      scientific cooperation.
AB  - Work-related musculoskeletal disorders (WRMSDs) have become a serious worldwide
      problem. At the same time a number of workers experience a problem in getting
      their WRMSDs acknowledged. As an attempt to solve these problems, Japanese school
      lunch cooks' working conditions were discussed at international scientific
      meetings and a detailed inspection was done at a Japanese school kitchen by
      Swedish researchers. It revealed that both national and international
      researchers' opinions coincided. Statements of medical views were written for
      several tangled cases in Japan and Sweden referring to both the national and
      international literature. As a result, these tangled cases were acknowledged
      officially as WRMSDs. New arbitrators and mediators of WRMSDs are required who
      can understand and communicate between the world of medical and labor sciences
      and also between the world of science and daily work life.

PMID- 17208842
TI  - Picture this: a work life photo layout.

PMID- 17208843
TI  - 'It almost doesn't matter what your job is, workers have health and safety issues
      on the job:' an interview with larry gregoire, president, international chemical
      workers council, ufcw.

PMID- 17208844
TI  - Introduction: Social responsibility and big oil--the last Maginot Line?

PMID- 17208845
TI  - The British offshore oil industry after Piper Alpha.
AB  - In 1998, the explosion of the Piper Alpha platform claimed 167 lives, making it
      the world's worst offshore oil disaster. Following this disaster, the U.K.
      offshore regulatory regime underwent a fundamental reconstruction which was based
      on the principles of self-regulation and goal-setting. This article argues that
      there has been no clearly discernable pattern of improvement in terms of offshore
      incidents since the post-Piper Alpha reforms. The authors attribute this lack of
      improvement to three principal factors, namely, the lack of effective workforce
      participation and representation in safety matters, the oil industry's strategic
      use of "veto points" and, lastly, the failure of the new regulator to police
      offshore safety and to adequately deter rogue operators.

PMID- 17208846
TI  - Offshore safety regulations in Norway: from model to system in erosion.
AB  - There are indications that the Norwegian oil province has experienced a decrease
      in incidents since the introduction of its external control system, which gives
      industry an important role in setting and maintaining safety standards. This
      article argues that much of the veneration of the Norwegian model is based on a
      misreading of the Norwegian offshore health and safety system. The author
      suggests that improvements in offshore safety in Norway were not caused by the
      adoption of the internal control system alone, but rather by a number of factors
      which included the introduction of the stringent Norwegian Work Environment Act,
      which gives union representatives the right to stop work when they feel safety is
      jeopardized, as well as the maintenance of strong offshore unions with a
      comprehensive network of trade union-appointed safety representatives.

PMID- 17208847
TI  - Safety and industrial relations in the Newfoundland offshore oil industry since
      the Ocean Ranger disaster in 1982.
AB  - Based on an examination of safety and industrial relations since the Ocean Ranger
      disaster, the article argues that government and industry changes have not fully
      addressed the problems that emerged from the investigation. Although the
      establishment of a single regulatory agency in the province is an improvement,
      some jurisdictional ambiguity remains and occupational health and safety
      regulations are still in draft form after their introduction more than ten years
      ago. Unionization is seen as an important step toward a safe workplace offshore,
      particularly in view of some current concerns: working schedules, training,
      evacuation, and search-and-rescue helicopters.

PMID- 17208848
TI  - Northern exposure.
AB  - The operators of Alaska's Alyeska pipeline have often claimed an outstanding
      record in preventing accidents and environmental damage. This article highlights
      that, contrary to these claims, Alyeska's operations have brought with them a
      life-threatening gamble with Alaska's fragile environment. The authors document
      how the operators of Alyeska have misled the public about the company's real
      safety record, while at the same time preventing employees from speaking out. As
      the oil companies consolidate globally, territorial entities such as Alaska can
      literally assume the character of an oil province.

PMID- 17208849
TI  - Afterword--Loaded dice: multinational oil, workers, and the state.

PMID- 17208851
TI  - Editorial: The continuing struggle for adequate compensation for injured workers.

PMID- 17208852
TI  - In search of a method: permanent disability assessment revisited.
AB  - How workers are compensated for the permanent consequences of their workplace
      injuries remains a hotly contested subject. The spreading misuse of the AMA
      Guides as the sole determinate of permanent disability has intensified the
      debate. This commentary highlights critical issues surrounding the AMA Guides.
      Finally, a restatement of the principles recommended for the assessment of
      permanent disability is set forth.

PMID- 17208853
TI  - The battle over workers' compensation.
AB  - Faced with lower profits and rapidly increasing premium costs in the 1980s,
      insurers and employer organizations cleverly parlayed the public perception of
      worker fraud and abuse in the workers' compensation system (that they helped to
      create) into massive legislative changes. Over the last decade, state legislators
      and governors, Republican and Democrat alike, have jumped on this bandwagon, one
      that workers and their allies have dubbed the workers' compensation "deform"
      movement. Alleging a "game plan" and a calculated campaign on the part of
      insurers and employers, the author looks at the major components of changes that
      were made, examines the elements of workers' compensation over which employers
      and insurers have gained control, and discusses Newt Gingrich's efforts to
      capitalize on employer and insurer fervor over the system. This campaign whistled
      through the country until it goaded the labor movement, injured workers, the
      trial bar, and others in Ohio in 1997 to organize themselves to stand up to
      employers by defeating the deform law through a ballot initiative. The article
      details that battle and suggests that similar voices can be achieved through a
      return to grassroots organizing and mobilization.

PMID- 17208854
TI  - The fetish of the objective finding.
AB  - Pressure is mounting for clinicians to rely solely on objective measures when
      evaluating workers with possible work-related disease. These measures are
      intended to largely supplant the worker's history as sources of information
      regarding diagnosis, work relatedness, and extent of disability. While seeming to
      promote more accurate and neutral evaluation methods, the underlying agenda is to
      reduce business costs by denying work-related illness and disability. Promoting
      the view of occupational health as the province of technical experts, the
      campaign for the objective finding silences workers as unqualified to comment.
      The methods proposed to enhance objectivity also suffer from significant specific
      shortcomings. To resist efforts to fetishize the objective finding, clinicians
      need to recognize the subjective elements of objective methods as well as the
      objective value of subjective data. This requires recognition of the central role
      of workers and histories in the clinical evaluation process.

PMID- 17208855
TI  - Moral hazard: a question of morality?
AB  - Economists use the term moral hazard to describe the tendency for insurance plans
      to encourage behavior that increases the risk of insured loss. Numerous economic
      studies have examined moral hazard effects in workers' compensation. Many of
      these have focused on the supposed propensity of workers to exercise less caution
      or to file more claims in response to increases in workers' compensation benefit
      levels. Although many authorities insist that moral hazard is a value-neutral
      concept, there are often pejorative connotations associated with contemporary
      discussions of moral hazard that intentionally or unintentionally disparage the
      motives of workers and undermine public support for workers' compensation
      programs. This article critically examines that literature and explores the
      conceptual underpinnings of economists' claims that employee moral hazard is
      rampant in workers' compensation. We examine the historical roots of moral hazard
      and its role in recent economic analyses of workers' compensation, consider the
      practical and ethical implications of that discourse, and offer suggestions for a
      truly value-neutral approach that would describe the system more fairly and
      accurately.

PMID- 17208856
TI  - Reporting of work-related musculoskeletal disorder (MSD) to workers compensation.
AB  - In contrast to theories of moral hazard, it appears that workers under-report
      cases to Workers' Compensation. In a population-based phone survey of work
      related MSDs, it was found that cases were more likely to be reported if they
      were called work-related by a doctor, had surgery, or took time off from work.
      Higher rates of filing were found for lower education, having a union at the
      workplace, working in manufacturing, and for blue-collar occupations. Fear of the
      consequences of filing was significantly related to filing, but was not a strong
      association. A lack of perceived management support and lower decision latitude
      was associated with a higher rate of filing. Perceived knowledge of the Workers'
      Compensation system was not associated with filing. In general, a broader
      perspective of looking not just at reported claims but also unreported work
      related illnesses is important for understanding both the magnitude of the
      problem as well as the impact of changes in Workers' Compensation laws.

PMID- 17208857
TI  - Word from the front lines: injured worker organizations speak out.
AB  - An injured worker, from her experience in the system, describes the flaws in the
      Workers' Compensation system. She employs information gathered from injured
      worker organizations around the country, the Workplace Injury Studies Institute,
      and the findings from a 1996 study by the RAND Institute for Civil Justice. She
      looks at fraud in the Comp systems, and the roles of medical providers,
      attorneys, and insurers. She also describes the climate of suspicion around
      claimants in the process: how it feels to be an injured worker, and to be
      followed and videotaped by a hireling of an insurance company, and how she
      watched a fellow claimant led out of a Comp board proceeding in handcuffs.

PMID- 17208858
TI  - A piece of history: Governor Olson of California calls for exclusive state
      workers' compensation fund in 1939.

PMID- 17208860
TI  - The 'morality' of occupational health.
AB  - Both ethics and law are based on value systems. George Lakoff has contributed to
      our understanding of the value systems that influence attitudes toward public
      issues in his book, Moral Politics: What Conservatives Know That Liberals Don't
      (University of Chicago Press, 1996). He argues that two antagonistic but co
      existing moral systems influence attitudes toward public issues. Both are derived
      from metaphors of family life and child development and the "morality" of
      allowing certain actions. One moral system stresses individual responsibility and
      risk-taking, the other empathy and mutual assistance. The tension between these
      value systems explains much in political debate; issues generally tend to fall on
      one side or the other. Occupational health and related issues, almost uniquely,
      have the unfortunate characteristic of falling short in both. Our best efforts
      may be judged "immoral" by the strictest interpretations of both systems, even
      when they are successful. The practical implication is that we must not accept
      this pattern of thinking. The work relationship is not like a family. It is
      important to separate issues in occupational health from this pattern of thinking
      in both professional and public discourse.

PMID- 17208861
TI  - Public health action to control hazards: how good should the evidence be?
      Reflections on the OSHA Ergonomics Standard hearings.
AB  - At the OSHA hearings regarding the Proposed Ergonomics Standard, confusion
      occurred between appropriate scientific evidentiary criteria for initiating
      clinical interventions for individual patients as opposed to the evidence needed
      to justify public health protection interventions directed at controlling
      hazardous exposures for entire populations. We assert that clinical interventions
      have little relevance to the standard proposed at that time. We summarize for the
      record why this prerequisite is neither technically feasible nor ethically
      appropriate for public (population) health action to control hazards. Further, we
      advocate reasonable cause criteria for public health hazard control as the
      appropriate basis for deciding whether to proceed with implementing abatement
      policies, for a potential health threat to a population.

PMID- 17208862
TI  - Natural assets reform campaign: should progressives sign on?

PMID- 17208863
TI  - The new wars that are upon us.
AB  - In this speech that he delivered to an AFL-CIO health and safety conference only
      weeks after the disasters of Sept. 11, 2001, the Secretary-Treasurer of the AFL
      CIO looks at the harsh new world for labor and for worker health and safety. He
      links his viewpoint, too, to the policy changes resulting from George Bush's
      installation as President only a few months earlier: "We are witnessing one of
      the most anti-worker administrations in recent memory, perhaps in the entire
      history of this country." Then, he tells where the union battles of the future
      will be fought.

PMID- 17208864
TI  - Ergonomics battle is about who controls work.

PMID- 17208865
TI  - A case study of OSHEP's training partnership with the American Standard
      Corporation's Trenton facility and GMP local 175.
AB  - This case study examines the evolution and impact of a training partnership
      between the Rutgers University/N.J. Industrial Union Council's (IUC) Occupational
      Safety and Health Project and the American Standard Corporation's Trenton
      facility. The study draws on on-site interviews with three employees who played a
      key role in the training program as well as survey data from a broader cross
      section of the facility's workforce. Insights about the impact of training are
      viewed within the context of the adult education and evaluation literature,
      particularly studies focusing on participatory, interactive training techniques.
      Committed activists, a supportive union and management, and the infusion of
      skills and ideas from the Rutgers/IUC worker-to-worker health and safety program
      are viewed as key factors in understanding developments at the facility. In
      addition, the study emphasizes the importance of relationships developed between
      union activists, facility management, and the OSHEP training staff. On January 2,
      2001, the corporation announced plans to shut down the facility within the year,
      and plans for training the rest of the work force were dropped. Although the site
      specific training program was cut short, this case study traces changes in the
      plant's health and safety culture that occurred over a three-year period.

PMID- 17208866
TI  - Production and reproduction: the issues involved in reconciling work and
      pregnancy.
AB  - Quebec legislation in occupational health contains a measure that gives pregnant
      workers the right to demand healthy and safe work conditions so that they can
      continue working while they are pregnant. About one-third of pregnant workers
      exercise this right every year. Nonetheless, even though the legislation's goal
      is to favor continued employment, more than 75 percent of the female workers who
      are eligible for protective reassignment are, in fact, not reassigned to other
      work stations or tasks, and instead must stop working. The results presented here
      stem from research intended to improve our understanding of the difficulties that
      arise in the workplace when the organization of work has to be reconciled with
      pregnancy. In telling us their experiences, the 51 pregnant workers we
      interviewed gave us their definition of "reconciliation." They did this by
      identifying the elements and areas of their occupational and family
      responsibilities that hindered or favored this reconciliation. They thus brought
      to light the predominant role that social relationships play in these situations.
      The comments of the women we met shed light on work conditions and organizations
      whose characteristics, once identified, suggest some of the changes needed to
      make this reconciliation possible.

PMID- 17208867
TI  - Report from Morelia: towards the formation of "The Observatory of the Americas".

PMID- 17208871
TI  - Ideology Tzars in federal science: the specter of Trofim Lysenko.

PMID- 17208873
TI  - Work organization and CVD.

PMID- 17208872
TI  - The state of occupational health in community Europe: from top-down reform to a
      renewal of trade union action?
AB  - Working conditions in Europe are getting worse, due to changes in work
      organization, including intensification and increasing insecurity. A critical
      assessment of the state of prevention in Europe remains essential. Trade union
      organizations on the Luxembourg Advisory Committee on Safety, Hygiene and Health
      Protection at Work drafted a document on what Community occupational health
      policy should seek to achieve. In June 2001, the ETUC Executive Committee adopted
      a resolution based on the document. This article discusses the trade union
      strategy. The first step is to critique the few existing indicators. To a
      considerable extent, they actually conceal the health problems of work. The
      statistics on occupational disease reflect, above all, characteristics of the
      various national systems of benefits but say little about the real state of
      workers' health. "Traditional" risks still cause tens of thousands of deaths and
      injuries every year. Risks associated with work organization are increasing
      steadily. The intensification of work is an important aspect of the
      reorganization of production processes and is associated with major changes in
      work management and organization. At the same time, the spread of Taylorized work
      procedures in certain sectors (probably correlating strongly with work performed
      by women in both services and some branches of industry) and the introduction of
      management methods may be summarized in the phrase "controlled autonomy." It
      involves shifting some of the supervisory burden to the level of the team, which
      destroys collective solidarity and detracts from the conditions under which work
      can contribute to mental health. Labor insecurity has been facilitated by the
      reappearance of mass unemployment and technological changes. Work has become
      increasingly less "sustainable" and companies are swamping society with the real
      social costs of their appetite for profit. In seeking harmonization, we must
      ensure consistent legislation based on the fundamental principles of the
      Framework Directive. Thus, trade unions demand that all risk factors be covered
      by directives based on effective preventive approaches. The new language of risk
      assessment and broadened approach to occupational health may initiate a process
      that (i) makes the invisible visible; (ii) moves on from observing individual
      complaints to collective analysis; and (iii) formulates a collective strategy
      based on identifying what "can be tolerated no longer."

PMID- 17208874
TI  - Worksite tobacco control policies and labor-management cooperation and conflict
      in New York State.
AB  - This article summarizes the origins and implementation of labor-management
      negotiated tobacco control policies in public workplaces in New York State during
      the 1980s and 1990s. It is an in-depth case study that illustrates the
      confrontation and cooperation among three main social actors involved in the
      design and implementation of workplace smoking policies: public-sector labor
      unions, public health professionals, and state managers. The policy debates,
      legal, and political issues that emerge from this history suggest hopeful avenues
      for improving the dialogue and cooperation on the design and implementation of
      workplace smoking policies between and among public health professionals,
      managers, and labor union leaders in the United States. Understanding how these
      parties can reach agreement and work together may help tobacco control advocates
      and labor leaders join forces to enact future tobacco control policies.

PMID- 17208875
TI  - Is there hope for the global environment? A discussion of prospective parent
      corporation liability for a subsidiary's environmental practices abroad.
AB  - U.S. parent corporations should be held liable for environmental pollution caused
      by their foreign subsidiaries. The Comprehensive Environmental Response,
      Compensation and Liability Act (CERCLA) already holds parent corporations liable
      in some ways for pollution caused by domestic subsidiaries. Regulations similar
      to CERCLA's could be applied extraterritorially and would be facilitated by
      abrogation of two common law principles: limited liability and forum non
      conveniens. Extraterritorial application of U.S. environmental regulations would
      greatly enhance transnational corporations' environmental behavior and facilitate
      just adjudication of plaintiffs' claims against irresponsible companies.
      Establishing the corporate parent's liability and upholding U.S. environmental
      standards in such cases would end many current hazardous practices that create
      pollution in developing countries.

PMID- 17208876
TI  - The federal ergonomic standard in Brazil: its social historic process.
AB  - Brazil has a Federal Ergonomic Standard enacted in 1990 that attracts the
      attention of practitioners in occupational health and safety fields because it is
      viewed symbolically as a political gain and because of its technical advances.
      The 1990 ergonomic standard modified a former one that was issued within a set of
      28 occupational health and safety regulations established in 1978. This article
      focuses on the social and historical steps in a persistent workers' struggle for
      a healthier work environment in the late 1980s that resulted in this federal
      standard as a "command-and-control" regulation pioneering a wide tripartite
      process of policy-making in Brazil.

PMID- 17208877
TI  - Senator Waxman writes to the EPA over a pesticides conference.

PMID- 17208878
TI  - The occupational injury and illness crisis within the health care industry, and
      its relationship to the current mechanisms for financing the Massachusetts Health
      Care System.

PMID- 17208880
TI  - Chinese workers never die: immortality or elusive statistics?
AB  - Have Chinese workers discovered immortality? No, but it appears that some of
      their employers may have--at least on paper.

PMID- 17208881
TI  - Alan Dalton: fearless campaigner who took on deadly industries.

PMID- 17208882
TI  - Nanotechnology and environmental and public health considerations.
AB  - Nanotechnology has arrived on the scene much as did predecessor technologies-
      hailed for its purpose and accepted with enthusiasm amid bursts of research,
      funding, and news of creative applications. But the early efforts to consider its
      environmental aspects have been small even though the implications for
      environmental and public health are broad. A well-crafted policy framework is
      needed, one linked to a clearer understanding of the direct and indirect effects,
      benefits, and risk of nanotechnology. A precautious approach would foster policy
      interventions to prevent harms by slowing developments where the risks are high
      and focus scientific effort on dispelling ignorance and uncertainty, especially
      in those areas where the consequences of being wrong are substantial. This kind
      of approach also would impose the burden of demonstrating the safety of the
      technology primarily on its proponents. The process of producing guidelines for
      other technologies is considered.

PMID- 17208883
TI  - The chemical wars.
AB  - The culture of economic growth and rapid innovation has led the chemical industry
      to contaminate tens of thousands of locales with hazardous chemicals that are
      poorly understood. As a result, the chemical industry finds itself at war with
      citizens who are troubled by the widespread dissemination of industrial poisons
      and alarmed by the power and unaccountability of the corporations themselves. The
      current chemical regulatory system has not provided an effective or reassuring
      restraint on chemical contamination because it relies heavily on a technique
      called risk assessment instead of the newer approach being tried now in Europe
      and elsewhere, the precautionary principle. Here's a riddle to keep you up at
      night: How come, at a time when the environmental movement is stronger and richer
      than ever, our most pressing ecological problems just get worse? It's as though
      the planet has hit a Humpty-Dumpty moment in which unprecedented amounts of
      manpower and money are unable to put the world back together again.

PMID- 17208884
TI  - The problem of current toxic chemicals management.
AB  - In this article, we explore the limitations of current chemicals management
      policies worldwide and the evolution of new European, International and U.S.
      policies to address the problem of toxic chemicals control. It is becoming
      increasingly apparent that current chemicals management policies in Europe and
      the United States are inadequate. There is a general lack of toxicity and
      exposure information on chemicals in commerce and the vast majority of chemicals
      were considered safe until proven guilty in legislation. Governments must then
      prove each chemical is dangerous through a slow and resource-intensive risk
      assessment process. For more than a decade, Nordic countries, such as Denmark and
      Sweden, have actively promoted integrated chemicals policies to address
      contamination of critical waterways. They have successfully used a variety of
      voluntary and mandatory policy tools, such as education, procurement, lists of
      chemicals of concern, eco-labeling, research and development on safer
      substitutes, and chemical phase-out requirements, to encourage companies using
      chemicals to reduce their reliance on harmful substances and to develop safer
      substitutes. While previously isolated to particular countries, innovative and
      exciting European-wide policies to promote sustainable chemicals management are
      now moving forward, including the recently published draft Registration,
      Evaluation and Authorization of CHemicals (REACH) policy of the European Union. A
      sweeping change in chemicals management policies in Europe is inevitable and it
      will ultimately affect manufacturers in the U.S. and globally. The European
      movement provides an opportunity to initiate a discussion on integrated chemicals
      policy in the U.S. where some innovative initiatives already are underway.

PMID- 17208885
TI  - Health systems in Eastern Europe--the impact of reform.
AB  - The article reviews the socio-economic security of health sector workers across
      Eastern Europe and suggests that decision-makers and their advisers should
      reconsider reforms which presuppose job cuts and labor-saving technologies in
      countries with little alternative employment, few unemployment benefits and scant
      investment capital. It points out that a narrow focus on doctors, as change
      agents, will exclude many of the care providers who actually determine how
      patients experience health services. It argues that involving all occupational
      groups in change, extending social dialogue and enhancing stewardship have a
      better chance of ensuring acceptance of the reform agenda and so the delivery of
      quality care.

PMID- 17208887
TI  - OSHA and home work.

PMID- 17208886
TI  - Confronting the continuing problem of asbestos in Scotland: report on a Scottish
      public sector initiative for the 21st century.
AB  - This article outlines a Scottish initiative for tackling asbestos in local
      authority (municipal) buildings. It explores issues surrounding municipal
      asbestos usage, financial costs, health and safety management and control and
      also support systems to assist asbestos victims and their families. Some
      solutions are offered to address these issues.

PMID- 17208888
TI  - The WTO asbestos case and its health and trade implications.

PMID- 17208889
TI  - Leukemia in petroleum refinery workers: a review of recent studies.
AB  - A previous review of the published epidemiologic literature on cancer risk in
      workers in the petrochemical industry indicated excess risks of leukemia and
      several other cancers. Here we update this review, focusing on the risk of
      hematologic cancers (for example, leukemia and lymphoma) reported in studies of
      oil refinery workers published in the last ten years. Limitations of recent
      studies are discussed, including the dilution of highly exposed groups of workers
      with workers with little or no exposure. We consider the evidence for a "safe
      level" or threshold of benzene exposure in the light of its ability to cause
      several types of damage, including damage to stem cells which may cause a variety
      of malignancies. We conclude that there is evidence of a slight increase in
      mortality from leukemia among oil refinery workers, particularly among those
      employed before 1950. And continuing exposures to benzene and other carcinogens
      occurring in this industry should be controlled.

PMID- 17208890
TI  - Principles of efficiency and occupational health: the case of the nuclear
      industry.
AB  - Reducing risks in the nuclear industry necessarily exposes maintenance workers to
      ionizing radiation. In the early 1980s, the French industry started outsourcing
      certain work operations, including nearly all maintenance. The goal was seen as
      one of reducing costs. But an important result is a shift in the category of
      workers receiving radiation doses. External workers receive 80 percent of annual
      collective doses recorded at nuclear sites, with average individual monthly
      dosages in an irradiated area eleven to fifteen times more elevated than those of
      workers in the French electric company. Nuclear producers strictly observe
      regulatory exposure limits by managing jobs by doses and externalizing the
      problem. An employee who reaches the dosage limit is banned from the plant.
      Qualified permanent employees do not do the work that is most costly in dosage.
      Outsourcing the risky work prevents challenges from unions and public officials,
      and firms can claim that radiation exposures are controlled and do not endanger
      workers' health. The problem, a terrible contradiction at the heart of the
      industry, has been socially constructed to be invisible.

PMID- 17208891
TI  - The costs of work-related musculoskeletal disorders in automotive manufacturing.
AB  - Inadequate application of ergonomic principles to the design of workplaces and
      individual jobs has adverse consequences for worker health and safety, especially
      in terms of strains, sprains, and other musculoskeletal disorders. In addition to
      the human pain and suffering, other losses are externalized to workers, with
      adverse financial and psychosocial impacts. There are also costs to employers
      through workers' compensation claims, scrap, and decreased production quality,
      medical insurance premiums, labor turnover, and adverse impacts on labor
      relations, although many of these are not linked by traditional accounting
      methods to ergonomic problems per se. Data collected in five plants of two major
      U.S. automotive manufacturing companies in the last decade have been used to
      estimate some of the costs associated with work-related musculoskeletal disorders
      (MSDs), only some of which resulted in workers compensation claims. In one plant
      in 1984-85, the payroll cost of all back and shoulder disorders was at least $320
      per year per worker, not including workers' compensation premiums or claims paid.
      A large proportion of these costs were accrued by "unreported" cases, that is,
      cases that either had never been reported to the plant clinic or had been
      reported in the past and were considered administratively to have recovered. In
      the other four plants, annual costs associated with in-plant medical visits for
      MSDs in 1989-93 were almost as high as those resulting from compensation claims.
      At least one-half of these disorders were estimated to be attributable to
      physical ergonomic exposures in the workplace and thus preventable. These data
      are consistent with estimates by others that the real costs to employers are at
      least two to three times the amount paid in workers' compensation cases, and that
      at least 50 percent of all work-related musculoskeletal disorders among the
      working population could be prevented by appropriate ergonomic job design.
      Furthermore, recent experience with ergonomics programs in various manufacturing
      and service settings shows that they are cost-effective in reducing morbidity,
      work absenteeism, and workers' compensation claims; payback periods for workplace
      modifications can be as short as a few months. Further investigations should
      explore the reasons that monetary costs and other impacts on profitability do not
      always motivate employers to improve working conditions.

PMID- 17208892
TI  - Recognition of work-related diseases: an original collaborative project in
      Quebec.
AB  - Establishing the causal link between disease and working conditions is no easy
      task. In Quebec, an original collaborative project combining epidemiology,
      community organization, and medical care has evolved over the years in order to
      promote the recognition of work-related diseases, particularly among non
      unionized workers. This article will describe this innovative project as well as
      its achievements, strengths, and weaknesses.

PMID- 17208893
TI  - Industrial hygiene review of three manufacturing facilities in Senegal: findings
      and key questions.
AB  - An industrial hygiene review was conducted in pesticide, asbestos, and cement
      manufacturing facilities in Senegal to provide the Senegalese Ministry of Labor
      with recommendations for improving working conditions. Findings show severe under
      reporting of occupational illnesses, and major short-comings in terms of worker
      training, personal protective equipment use, emergency planning, and other
      traditional industrial hygiene controls. Despite these findings, a comparison
      between observed conditions and the proposed Occupational Safety and Health
      Administration (OSHA) Safety and Health Program Management standard shows that
      these companies would probably not be considered grossly non-compliant by U.S.
      standards, and suggests that strong regulatory enforcement of actual working
      conditions remains a necessity. This analysis also suggests that compliance with
      the proposed standard would not in itself assure that such dire shortcomings as
      were observed could not legally exist here in the United States. Key differences
      between the political economies of developing nations and the United States
      suggest that improving working conditions requires a comprehensive planning
      effort addressing poverty reduction, environmental considerations, and economic
      growth. Three fundamental questions are proposed which should be addressed to
      improve working conditions in Senegal.

PMID- 17208897
TI  - Comparison of single and boosted protease inhibitor versus nonnucleoside reverse
      transcriptase inhibitor-containing cART regimens in antiretroviral-naive patients
      starting cART after January 1, 2000.
AB  - BACKGROUND: Few published studies have considered both the short- and long-term
      virologic or immunologic response to combination antiretroviral therapy (cART)
      and the impact of different cART strategies. PURPOSE: To compare time to initial
      virologic (<500 copies/mL) or immunologic (>200/mm3 cell increase) response in
      antiretroviral-naive patients starting either a single protease inhibitor (PI; n
      = 183), a ritonavir-boosted PI regimen (n = 197), or a nonnucleoside reverse
      transcriptase inhibitor (NNRTI)-based cART regimen (n = 447) after January 1,
      2000, and the odds of lack of virologic or immunologic response at 3 years after
      starting cART. METHOD: Cox proportional hazards models and logistic regression.
      RESULTS: After adjustment, compared to patients taking an NNRTI-regimen, patients
      taking a single-PI regimen were significantly less likely to achieve a viral load
      (VL) <500 copies/mL (relative hazard [RH] 0.74, 95% CI 0.54-0.84, p = .0005);
      there was no difference between the boosted-PI regimen and the NNRTI regimen (p =
      .72). There were no differences between regimens in the risk of >200/mm3 CD4 cell
      increase after starting cART (p > .3). At 3 years after starting cART, patients
      taking a single-PI-based regimen were more likely to not have virologic
      suppression (<500 copies/mL; odds ratio [OR] 1.60, 95% CI 1.06-2.40, p = .024),
      while there were no differences in the odds of having an immunologic response
      (>200/mm3 increase; p > .15). This model was adjusted for CD4 and VL at starting
      cART, age, prior AIDS diagnosis, year of starting cART, and region of Europe.
      CONCLUSION: Compared to patients starting an NNRTI-based regimen, patients
      starting a single-PI regimen were less likely to be virologically suppressed at 3
      years after starting cART. These results should be interpreted with caution,
      because of the potential biases associated with observational studies.
      Ultimately, clinical outcomes, such as new AIDS diagnoses or deaths, will be the
      measure of efficacy of cART regimens, which requires the follow-up of a very
      large number of patients over many years.

PMID- 17208899
TI  - The politics of ergonomics.

PMID- 17208898
TI  - Once-daily abacavir/lamivudine/zidovudine plus tenofovir for the treatment of HIV
      1 infection in antiretroviral-naive subjects: a 48-week pilot study.
AB  - PURPOSE: To assess the safety and efficacy of a 4-drug, 3-tablet, once-daily (qd)
      regimen consisting of abacavir/lamivudine/zidovudine (ABC/3TC/ZDV; 2 tablets) and
      tenofovir (TDF) in antiretroviral-naive patients with plasma HIV-1 RNA 30,000
      copies/mL at 48 weeks. METHOD: All participants received ABC/3TC/ZDV (300/150/300
      mg) and TDF (300 mg) qd in this pilot, open-label, multicenter study. Intent-to
      treat (ITT) analyses were conducted to evaluate virologic and immunologic
      efficacy. RESULTS: Of the 123 participants enrolled, 52 (42%) prematurely
      discontinued study for adverse events (14), were lost to follow-up (13), had
      virologic nonresponse (12), and withdrew for other reasons (13). At week 48, by
      ITT missing=failure analysis, 41% (51/123) and 51% (63/123) of participants had
      plasma HIV-1 RNA <50 copies/mL and <400 copies/mL, respectively; by ITT-observed
      analysis, 75% (51/68) and 93% (63/68) had plasma HIV-1 RNA <50 copies/mL and <400
      copies/mL, respectively; 11% (14/123) met virologic nonresponse criteria. Median
      week 48 change in CD4+ cell count from baseline was +127 cells/mm3. Median week
      48 changes from baseline for fasting lipids were as follows: cholesterol (-9
      mg/dL), HDL (+1 mg/dL), LDL (-9 mg/dL), and triglycerides (-4 mg/dL). CONCLUSION:
      A high rate of premature discontinuations contributed to the overall suboptimal
      virologic response to ABC/3TC/ZDV+TDF qd; however, the regimen was not associated
      with high rates of virologic failure previously observed with TDF+ABC/3TC.

PMID- 17208900
TI  - Overloading is not sustainable.

PMID- 17208901
TI  - Democratic participation: a critical element of precautionary public health
      decision-making.
AB  - The precautionary principle is increasingly discussed in debates about threats to
      health and the environment, particularly when government actions might inhibit
      free trade. It is gaining recognition as an overarching principle of decision
      making, one that underlies efforts for sustainable development. Pronouncements
      about the precautionary principle have focused generally on the responsibility of
      government to act in the face of uncertainty and the shifting of burdens onto
      proponents. This assumes that government will have the resources, knowledge,
      expertise, and will to act. The role of the public those who may be affected by
      environmental degradation or their representatives is mostly missing from the
      discussions. This article outlines a rationale for why participation is critical
      and explores the theory of citizen participation. The article also describes
      participatory models used around the world, primarily examples of citizen
      participation though various models also exist for workers.

PMID- 17208902
TI  - Footprints of a giant.
AB  - The chemical accident at the Union Carbide factory in Bhopal, India in 1984 has
      killed 16,000 people so far and tens of thousands of others are still seriously
      ill. A physician reviews some of their ailments and comments on the lack of
      medical services available to them and of knowledge about long-term health
      effects of the exposures. Documenting observed effects also is underway, aiming
      to define the symptoms, propose effective management, and help direct research
      efforts. Information may be provided to relief and rehabilitation efforts and may
      even be helpful in the ongoing criminal suit against Union Carbide. The Indian
      government, meanwhile, suspended its research efforts in 1994, even though many
      health effects may not develop for years.

PMID- 17208903
TI  - A clinic succeeds Kern's in Rhode Island.
AB  - A new Occupational and Environmental Health Center has opened in Providence,
      Rhode Island, the successor to the one operated by Dr. David Kern until 1997 when
      he published research that identified a new occupational respiratory disease
      among patients there and thereby drew a storm of controversy involving his
      program, Memorial Hospital, and Brown Medical School. The new independent clinic
      is the result of cooperative work among a number of medical and occupational
      organizations in the state.

PMID- 17208904
TI  - Organized labor, public health, and tobacco control policy: a dialogue toward
      action.
AB  - An action-oriented conference, Organized Labor, Public Health, and Tobacco
      Control Policy, was held in September 2000 in Boston, Massachusetts. Labor union
      leaders, tobacco control and public health activists, researchers, and
      practitioners met for two days to: 1) learn about existing labor-based tobacco
      control initiatives; 2) educate one another about resources, barriers, and
      opportunities for labor-public health joint action on tobacco policy; 3) and
      identify where agendas overlap and form the basis for specific next steps in
      collaborative efforts in tobacco-related research, training, and advocacy. This
      report summarizes presentations and participant discussions to inform readers of
      the information exchanged and of the enthusiasm shared by conference participants
      translated into a set of joint recommendations for increased labor-based and
      joint labor-public health action to reduce the burden of tobacco on working
      people.

PMID- 17208905
TI  - Field conditions for agricultural workers in the El Paso, Texas region.
AB  - Agricultural workers labor long hours under difficult conditions in many of the
      nations fields and orchards. Agricultural workers are primarily minority
      populations, the most dominant group being Hispanic/Latino. The Rural Coalition
      and the Environmental and Occupational Health Sciences Institute were funded
      under the National Institute of Environmental Health Sciences (NIEHS)
      Environmental Justice Program, to investigate health and environmental issues
      that impact agricultural workers along the Texas-Mexican border area. A Spanish
      language field conditions survey was developed and distributed to the workers
      entering the Sin Fronteras Organizing Project in El Paso, Texas. There were 841
      valid surveys collected and analyzed for the calendar year 1998. Workers age mean
      was 51, with 18.6 years of work experience in agriculture. In the time period
      surveyed, workers labored for 7.2 hours per day. The primary crop in which they
      worked were chilies. Of particular concern were issues concerning food, water,
      and hygiene. Almost all workers stated they had access to fresh drinking water
      (97 percent), 20 percent did not have access to food, and 30 percent were offered
      alcohol for purchase. Almost one-third of the workers did not have water
      available for hand washing in the field. Only 8 percent of the workers reported
      pesticides used in the fields in which they were working; this number is lower
      and may be a reflection of the improved training and caution taken by the
      workers. Clearly additional research in the area of field conditions and the
      impact and enforcement of state and federal regulation needs to be carried out.

PMID- 17208906
TI  - Housing conditions and respiratory health in a Boston public housing community.
AB  - OBJECTIVES: To determine frequency of and possible associations between
      environmental housing factors and self-reported respiratory symptoms in public
      housing. METHODS: We used a community-participatory method in which trained
      residents conducted in-person interviews with a random sample of 53 households in
      one housing development in Boston, Massachusetts. RESULTS: Environmental factors
      suspected of affecting respiratory health that were reported by more than 30
      percent of respondents included: Moisture (43 percent), mold (43 percent), cracks
      in walls, floors and ceilings (49 percent), sewage leaks (33 percent),
      unexplained odor (35 percent), use of air fresheners (91 percent), use of gas
      ovens for heating (38 percent), no vent for the oven (74 percent), stuffy air (66
      percent), overheating at least part of the winter (73 percent), cockroaches (70
      percent), rodents (40 percent), pets (39 percent), frequent renovations (40
      percent), repeated requests for repairs (52 percent), dust from construction (45
      percent), use of more than three hazardous household products (32 percent),
      vehicle traffic nearby (81 percent), and smoking in the household (57 percent).
      Forty percent of respondents reported having asthma. Respondents also reported
      that 56 percent of their children had asthma. Forty percent of respondents
      reported wheeze and 48 percent reported coughing or sneezing episodes in the
      preceding month. We found the following positive statistically significant
      associations, adjusted for age, sex, Black or Hispanic origin, and years lived in
      public housing: wheeze with moisture problems (OR = 4.8; CI = 1.2, 19.3), sewage
      leaks (OR = 6.3; CI = 1.3, 30.3), odor (OR = 7.5; CI = 1 .4, 39.0), cracks in
      walls,floors and ceilings (OR = 8.6; CI 1.9, 38.0), and frequency of renovations
      (OR = 9.8; CI = 1.8, 54.4); cough with moisture problems (OR = 5.3; CI = 1.3,
      20.8), stuffy air (OR = 4.4; CI = 1.2, 16.7), cockroaches (OR = 5.4; CI = 1.2,
      24.2), smoking (OR = 5.0; CI = 1.2, 20.5), odor (OR = 10.9; CI = 2.3, 53.0),
      cracks in walls, floors and ceilings (OR = 6.2; CI = 1.8, 22.3) and frequency of
      renovations (OR = 4.4; CI = 1.1, 17.5); and sneeze with cockroaches (OR = 5.2; CI
      = 1.1, 24.2), stuffy air (OR = 6.3; CI = 1.5, 26.5), cracks in walls, floors and
      ceilings (OR = 6.3; CI = 1.7, 23.1), repeated requests for repairs (OR = 5.6; CI
      = 1.4, 21.5), and construction dust (OR = 15.6; CI = 2.2, 112.3). CONCLUSIONS:
      Housing conditions that affect respiratory health were common in this public
      housing development. Self-reported rates of respiratory symptoms and asthma were
      extremely high. Statistical associations between housing conditions and
      respiratory symptoms in the preceding month were frequently positive and
      sometimes statistically significant. Engaging community residents strengthened
      the research process.

PMID- 17208907
TI  - Characterization of the New Jersey lead hazard control workforce.
AB  - Individuals performing lead evaluation and abatement activities in New Jersey
      must complete certified training, an examination, and have a state permit card.
      Key demographic information was collected and summarized to describe this newly
      emerging lead workforce, to enhance lead training, to identify education and
      outreach needs, and to promote environmental justice. Summarizing these data also
      will assist other states implementing similar lead training and certification
      programs. As of June 30, 1998, the New Jersey Department of Health and Senior
      Services (NJDHSS) issued 2,370 permits to individuals in six disciplines. The
      lead workforce s average age was 38 years and 88 percent male. Most females were
      in the Inspector/Risk Assessor and Worker-Housing and Public Buildings (HPB)
      disciplines. Eighty percent of the workforce resided in New Jersey. Whites and
      Asians/Pacific Islanders were more educated than Hispanics or Blacks and a
      greater proportion of them were employed in the more skilled disciplines.
      Inadequate work experience may have prevented Blacks from qualifying for the more
      skilled disciplines; for Hispanics, there was also a language barrier. Twenty
      nine percent of Workers and Supervisors had children less than six years of age
      residing in their household, which was higher than comparable state rates. The
      proportion of households with children under six years of age were similar for
      Black (32 percent), Hispanic (30 percent), and White (27 percent) households. The
      number of children less than six years of age per Black and Hispanic permittee
      was significantly higher than for Whites. Take-home lead issues and possible
      initiatives to promote minorities in the more skilled disciplines are discussed.

PMID- 17208908
TI  - Safeguards at risk: John Graham and Corporate America's Back Door to the Bush
      White House Excerpts from a Public Citizen report.
AB  - The non-profit consumer organization Public Citizen released an investigatory
      report in March about the activities of industry-backed academic John Graham,
      head of the Harvard Center for Risk Analysis, who has been nominated by President
      Bush to lead the Office of Information and Regulatory Affairs (OIRA) within the
      White House s Office of Management and Budget (OMB). Public Citizen said at the
      time that the appointment would give industry a back door to the White House and
      enable it to step up its campaign to dismantle basic consumer protections under
      the pretense of applying sound science. Graham s nomination poses troubling
      implications, Joan Claybrook, president of Public Citizen, said. Rather than
      being a fair-minded assessor, Graham would continue to conspire with the chemical
      polluters, the tobacco industry, automakers, the oil and gas industries and
      others to stop the issuance of safety protections. The Senate must delve into the
      many conflicts he would bring to the job and reject this nomination. Below, we
      excerpt two portions of the Public Citizen report. One shows Graham s many
      corporate relationships; the other explains his involvement in environmental
      tobacco smoke issues. The full report, including the references that are omitted
      here, is available at www.publiccitizen.org. The report was researched and
      written by Laura MacCleery, with assistance from Paul Schmitt, Debbie Quint,
      Daniel Becker, and Ed Ricci. Editorial assistance and direction were given by
      Joan Claybrook, Booth Gunter, Angela Bradbery, Melissa Luttrell and David
      Vladeck.

PMID- 17208910
TI  - ISO and the WTO: a report to the International Confederation of Free Trade
      Unions' Working Party on Health, Safety, and Environment.

PMID- 17208912
TI  - Editorial: A civil solution.

PMID- 17208913
TI  - The union, the mining company, and the environment: steelworkers build a multi
      stakeholder model for corporate accountability at Phelps Dodge.
AB  - This is a case study of ongoing relations between the Phelps Dodge mining
      company, a United Steelworkers local representing 560 employees at the company's
      Chino Mines in New Mexico, and an array of other concerned stakeholders. This
      case study shows that labor can be a full partner in environmental advocacy, and
      even take a leadership role in building a strong multi-stakeholder alliance for
      corporate accountability. While the case also shows that corporate jobs blackmail
      is alive and well in the global economy, the labor community-coalition that has
      emerged at the mining complex has broken some new ground. The approach taken
      attends to diverse stakeholder interests--cultural protection issues of Native
      American and Mexican-American ethnic groups; conservation, groundwater and Right
      to-Know issues of traditional environmental constituencies; and environmental
      liability and disclosure concerns of corporate shareholders. Among the key
      developments are: A new approach to corporate reporting to shareholders as an
      enforcement and right-to-know tool; The use of the internet as an information
      dissemination and action tool; The potential for environmentally needed
      improvements to serve as a receptor for employment of workers at a mine during
      periods of reduced production.

PMID- 17208914
TI  - Endocrine disruption comes into regulatory focus.
AB  - Endocrine disruption has come under regulatory scrutiny since the passage of 1996
      federal laws. The U.S. Environmental Protection Agency (EPA) convened the
      Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC) to develop
      recommendations for a screening and testing program to assess chemicals potential
      to disrupt hormone function. The committee's September 1998 consensus report is
      important because it signals that endocrine disruption is a threat which a
      responsible society has an obligation to address. Furthermore, the program will
      generate significant new toxicological data. However, shortcomings in the EPA
      program will include: inadequate low dose testing; lack of a screening assay that
      examines early developmental exposure; and mechanisms that substitute
      "functionally equivalent" information. Implementation will face serious hurdles:
      insufficient funding; realistic validation yardsticks; resolution of crucial
      scientific questions, and political will. A wide diversity of constituencies
      appeared before the EDSTAC during public meetings, and the public will stay
      engaged by commenting on EPA s proposed program and by nominating chemicals for
      inclusion in the program. A meaningful response to endocrine disruption exposes a
      fundamental flaw in traditional risk assessment. If there is no "safe" exposure,
      there is also no regulatory threshold to identify.

PMID- 17208915
TI  - Safety and health conditions, practices, and priorities for OSHA reform: a
      comparison of views of New Jersey union members and safety and health
      professionals.
AB  - This article draws on survey and interview data from New Jersey occupational
      health and safety professionals and union members to provide insights into the
      interactions among workers, management, unions, and health and safety
      professionals that shape work place conditions and practices. A substantial
      number of both professionals and union members reported: serious or very serious
      health and safety problems; limited access to effective resources for addressing
      these problems; and the presence of serious barriers to resolving these problems.
      Fewer than half of the union and professional respondents reported that effective
      participatory mechanisms such as union/management health and safety committees
      existed at their work sites, and many interview respondents described situations
      in which serious problems might be aired but seldom resolved.

PMID- 17208916
TI  - Feeling the heat: displaced tobacco workers in North Carolina.
AB  - Tobacco control is a successful public health movement, but little attention is
      being paid to what this success means for workers and communities who are
      economically dependent on tobacco. The social context of job loss for these
      workers remains largely unstudied. We conducted a case study of a cigarette
      manufacturing facility closure in Reidsville, North Carolina and report on the
      effects of the closure for workers and the community. Results suggest the need
      for: 1) worker education directed toward developing skills for jobs that pay
      family-supporting wages, and 2) community-driven strategies to attract new
      businesses that offer such jobs. Public health organizations, labor unions,
      community development groups, business representatives, civic leaders, academic
      institutions, and others should unite in efforts to assist tobacco-dependent
      workers and communities to transition to other economic bases. These efforts
      should be funded by the tobacco industry.

PMID- 17208917
TI  - Economic miracle for what?: State workers' health in South Korea.
AB  - This article is a study of the state's role in workers health in South Korea
      during the period of the 1950s to 1980s in which South Korea achieved its
      economic success through a series of economic development plans. The state's role
      in the protection of workers health will be examined by investigating the
      historical development of two main welfare state programs, workers' compensation
      and national health insurance, as the pillars of state policies on workers
      health. In contrast to the state's direct intervention in economic development, I
      will argue, the key characteristics of both workers' compensation and national
      health insurance are the state's minimal organizational and financial costs and
      the relative autonomy of firm managers. Also, the state first restricted the
      scope of beneficiaries to the core group of manufacturing and mining workers and
      then gradually expanded it over a long period of time. I will argue that such
      features suggest a strong dependence on business by the Korean welfare state
      programs that contradicts the image of a strong state that the scholars of East
      Asian states often claim.

PMID- 17208918
TI  - Shop floor safety initiatives: the example of atmospheric testing in
      telecommunications cable vaults.
AB  - Strategies for occupational safety and health campaigns often overlook the
      possibilities afforded by initiatives centered in the workplace itself, as
      opposed to those focused, for example, at the bargaining table or in the
      legislature. Workers themselves sometimes may be more cognizant and informed of
      immediate health and safety issues than are their union representatives, and may
      formulate innovative or unorthodox approaches to hazard remediation. Such
      approaches may in fact succeed despite ineffectual contract language or weak
      regulatory protection. This article examines a successful struggle by a small
      group of telecommunications technicians to get the employer to revise its
      obsolete procedures for atmospheric testing of unventilated, underground cable
      vaults. It demonstrates that increased consideration should be given to shopfloor
      actions and creative use of the grievance procedure as useful tools in the
      struggle for occupational safety and health.

PMID- 17208919
TI  - Resolution for the City of Oakland establishing a regional task force and policy
      on dioxin, public health, and the environment.

PMID- 17208920
TI  - Failure to enforce safety laws threatens lives of Tijuana workers.

PMID- 17208922
TI  - Image-based screening for the identification of novel proteasome inhibitors.
AB  - The proteasome is a new, interesting target in cancer drug therapy, and the
      proteasome inhibitor bortezomib has shown an effect in myeloma patients. It is of
      interest to efficiently discover and evaluate new proteasome inhibitors. The
      authors describe the development of an image-based screening assay for the
      identification of compounds with proteasome-inhibiting activity. The stably
      transfected human embryo kidney cell line HEK 293 ZsGreen Proteasome Sensor Cell
      Line expressing the ZsProSensor-1 fusion protein was used for screening and
      evaluation of proteasome inhibitors. Inhibition of the proteasome leads to
      accumulation of the green fluorescent protein ZsGreen, which is measured in the
      ArrayScan High Content Screening system, in which cell morphology is studied
      simultaneously. When screening the LOPAC(1280) substance library, several
      compounds with effect on the proteasome were found; among the hits were
      disulfiram and ammonium pyrrolidinedithiocarbamate (PDTC). Cytotoxic analysis of
      disulfiram and PDTC showed that the compounds induced cytotoxicity in the myeloma
      cell line RPMI 8226. The average Z' value for the assay was 0.66. The results
      indicate that the assay rapidly identifies new proteasome-inhibiting substances,
      and it will be further used as a tool for image-based screening of other
      chemically diverse compound libraries.

PMID- 17208923
TI  - Scintillation proximity assay as a high-throughput method to identify slowly
      dissociating nonpeptide ligand binding to the GnRH receptor.
AB  - Many nonpeptide antagonists of the gonadotropin-releasing hormone (GnRH)
      receptor, as well as other drug targets, possess a broad range of dissociation
      kinetic rate constants. Current methods to accurately define kinetic rate
      parameters such as K(on) and K(off) are time and labor intensive, prompting the
      development of a screening assay to identify slowly dissociating compounds for
      follow-up rate constant determination. The authors measured inhibition binding
      constants (K(i)) for GnRH receptor antagonists after 30 min and 10 h of
      incubation and observed several compounds with markedly decreased K(i) values
      over time (Ki(30 min)/Ki(10 h) > 6). They used scintillation proximity assay
      technology to perform these binding experiments because this homogeneous assay
      does not have a fixed termination end point as does filtration binding,
      permitting successive readings to be taken from the same assay plate over an
      extended period of time. They also used a quantitative method of kinetic rate
      analysis to confirm that a large disparity between a compound's K(i) value at 30
      min and 10 h could identify compounds that dissociate slowly. Thus, the K(i)
      ratio can be used to screen for and select compounds to test using more
      quantitative, albeit lower throughput methods to accurately define kinetic rate
      constants.

PMID- 17208924
TI  - Dignity and the challenge of dying in nursing homes: the residents' view.
AB  - BACKGROUND: human dignity is discussed in almost all public debates on the care
      of the dying, as well as in international policies for health and social care of
      older people. Because nursing homes are gaining importance as places where
      residents live out their lives in modern western societies and since there is
      evidence that end-of-life care in nursing homes lacks quality, there is a growing
      discussion on introducing improved end-of-life care in these institutions. In
      order to accomplish this, the view of those who are most affected is of utmost
      importance. OBJECTIVE: to explore the meaning of dignity with regard to end-of
      life issues from the perspective of older nursing home residents in western
      Germany. METHODS: this qualitative study is based on the Grounded Theory
      Approach, and the design included three steps of data generation; narrative
      interviews with residents of nursing homes constitute the main data pool (n = 20)
      of the results presented in this paper. Theoretical sampling was aimed at
      maximising the variety of organisational as well as residents' characteristics.
      Analysis of the transcripts was supported by Atlas/ti program and followed
      several different coding procedures and aimed at generating a concept of dignity.
      RESULTS: dignity was differentiated into intrapersonal dignity and relational
      dignity, socially constructed by the act of recognition. Social relations and
      encounters are a prerequisite for relational dignity, which underlines the
      vulnerability of nursing home residents' who increasingly lack social networks. A
      broad spectrum of attitudes and behaviour, which aimed at recognising dignity,
      was bundled under the category 'not being a burden'. In this light, dignity was
      challenged most by the threat of illness and having care needs. This was fostered
      by the perception of insufficient care in the nursing homes. In the light of this
      concept, death with dignity meant 'death at the right time', though the residents
      in the sample did not want to comment on the time of death, other than aspects
      like (i) being active to the very last, (ii) respecting one's will and being
      allowed to die, (iii) not being in pain, (iv) being amongst persons close to one
      (valediction and showing respect). CONCLUSION: the study emphasizes the high
      vulnerability of nursing home residents with regard to dignity. They place their
      dignity under the constraints of the need for help and care into question. This
      appears alarming, if one does not manage to, with the help of different ethics,
      obtain a new perspective on these phases of life. It is evident that the
      understanding of dignity is not solely individualistic and personal, but rather
      has a close relationship to social ideas of value, which ultimately influence the
      basic requirements of institutions in which 'frail old people' live.

PMID- 17208925
TI  - Death of a G-6-P-D deficient child with co-morbid HIV infection linked to
      scarification.
AB  - Facial scarification is a process of engraving marks on selected portions of the
      face at infanthood for various cultural purposes. It is a common cultural
      practice in Africa especially Nigeria. The induction is associated with fever and
      severe crying in infants. Usage of the same unsterile tools for the induction in
      different children and the unhygienic environment are possible means of
      contracting HIV infection. Occurence of G-6-P-D deficiency and malaria predipose
      to severe anaemia often requiring blood transfusion. Blood screening facilities
      are grossly lacking in most rural areas in developing countries. This report is
      on a 2-year-old male child who presented with facial marks, lacked G-6-P-D and
      died of HIV infection after a follow-up of 6 months. We suggest that HIV
      infection contracted from facial scarification in the presence of G-6-P-D
      deficiency caused the child's death.

PMID- 17208926
TI  - Dendritic cells suppress IgE production in B cells.
AB  - Ig class switch recombination (CSR) is triggered by the engagement of CD40 on B
      cells by CD40 ligand on T cells. In addition, recent studies have shown that
      dendritic cells (DCs) are able to directly control the CSR of B cells through B
      lymphocyte stimulator protein [or B cell activation factor belonging to the tumor
      necrosis factor family] and a proliferation-inducing ligand. We examined in this
      study the regulatory role of DCs in CSR and demonstrate that DCs selectively
      suppress IgE production from B cells stimulated by CD40 and IL-4 through two
      different mechanisms: by direct cell-cell interaction or by soluble factors
      including transforming growth factor-beta and IFN-gamma. In addition, distinct
      DCs utilize different mechanisms: immature bone marrow-derived dendritic cells
      (BMDCs) and primary lung DCs strongly inhibit IgE CSR. On the other hand, LPS
      induced mature BMDCs lose the ability to inhibit IgE CSR but still suppress IgE
      production by decreasing IgE protein expression. These results indicate novel
      regulatory functions of DCs on IgE production.

PMID- 17208927
TI  - TLR9 ligand enhances proliferation of rat CD4+ T cell and modulates suppressive
      activity mediated by CD4+ CD25+ T cell.
AB  - Toll-like receptors (TLRs) play a crucial role in the initiation of innate
      responses following microbial infection and also in adaptive immune responses by
      orchestrating the activation of different cell populations. TLRs are expressed at
      high levels in antigen-presenting cells and recent studies have demonstrated the
      expression and biological role of TLRs in mouse and human CD4(+) T cells. In this
      study, we analyzed TLR mRNA expression in rat CD4(+) T cells using stringent
      quantitative reverse transcription-PCR conditions enabling a direct comparison of
      the levels of each TLR. We show that TLR3, 5, 6 and 9 mRNAs are the highest TLRs
      expressed in rat CD4(+) T cells and that TLR5 mRNA is highly expressed in
      regulatory CD4(+) CD25(+) T cells. In addition, we show that the TLR9 ligand
      (TLR9L), CpG oligodeoxynucleotide, synergizes with anti-CD3 to induce
      proliferation of both CD4(+) CD25(-) and regulatory CD4(+) CD25(+) T cells and
      that TLR9L partially abrogates the suppressive activity mediated by regulatory
      CD4(+) CD25(+) T cells. This loss of suppression is in part due to the direct
      effect of TLR9L on effector T cells that are rendered more resistant to the
      regulation exerted by regulatory T cells. To our knowledge, this is the first
      study describing the expression of TLR mRNA in rat CD4(+) T cells and the
      capacity of TLR9L to directly regulate rat T cell responses. Thus, TLR9L may
      rapidly increase the host's adaptive immunity by expanding effector cells and
      also by attenuating the suppressive activity mediated by regulatory T cells.

PMID- 17208928
TI  - Mechanical stretch regulates TRPC expression and calcium entry in human
      myometrial smooth muscle cells.
AB  - Stretch is known to stimulate myometrial hyperplasia and hypertrophy in early
      pregnancy and uterine contraction at term. We propose that transduction of the
      stretch signal involves alteration of intracellular calcium signalling, including
      changes in transient receptor potential canonical (TRPC) isoform expression. The
      aim of the present study was to investigate the effect of prolonged mechanical
      (tonic) stretch in vitro on human myometrial smooth muscle cell calcium
      signalling and TRPC expression. Cells were cultured from myometrial biopsies,
      obtained from women undergoing elective Caesarean section at term, grown on
      Flexiplates and subjected to 25% tonic mechanical stretch for 1, 4 and 14 h. Time
      matched control cells were not stretched. Mechanical stretch (14 h) increased
      basal calcium entry and cyclopiazonic acid (CPA)-induced calcium/Mn(2+) entry (P
      < 0.05) in Fura-2 loaded cells. The calcium selectivity of CPA-thapsigarin
      induced inward currents, measured by patch clamp electrophysiology, was also
      increased in stretched cells compared with control cells (P < 0.05). Real time
      PCR and Western blot data demonstrated that TRPC3 and TRPC4 mRNA and TRPC3
      protein expression were increased by stretch (P < 0.05), respectively. These data
      support the hypothesis that uterine stretch modulates uterine growth and
      contractility in pregnancy via alterations in calcium signalling.

PMID- 17208929
TI  - The effects of oxygen concentration on in vitro output of prostaglandin E2 and
      interleukin-6 from human fetal membranes.
AB  - Labour at all gestational ages has clear biochemical parallels with an
      inflammatory response, typified by the increased output of prostaglandins (PGs)
      and cytokines within the pregnant uterus. The main sources are the fetal
      membranes, including the amnion, chorion and decidua, and it is well established
      that stimuli [bacteria, bacterial endotoxins, interleukin (IL)-1beta,
      corticotrophin releasing hormone and platelet activating factor], as well as
      negative regulators (progesterone and IL-10), control the net output of PGs and
      cytokines in vitro. In this study, we have investigated the effect of oxygen
      tension on fetal membrane biology, as a reconsideration of the literature
      suggests that fetal membranes are normally exposed to approximately 3% O(2)
      (approximately 20 mmHg) in vivo, rather than the 20% O(2) (150 mmHg) used for in
      vitro culture. The output of prostaglandin E(2) from non-activated fetal
      membranes in response to IL-1beta was decreased by approximately 80% at 16 and 24
      h of culture, whereas the inhibition of IL-6 production was time-dependent,
      reaching 90% after 16 h and 50% after 24 h. Tissues obtained after labour (or
      after the activation of inflammatory processes leading to labour) were not
      inhibited by the low levels of oxygen, indicating that only before the onset of
      labour does oxygen regulate fetal membrane biology. The data identify oxygen as a
      regulator of fetal membrane inflammatory functions during human pregnancy, and
      its mechanism of action requires further study.

PMID- 17208930
TI  - Asthenoteratozoospermia in mice lacking testis expressed gene 18 (Tex18).
AB  - Testis expressed gene 18 (Tex18) is a small gene with one exon of 240 bp, which
      is specifically expressed in male germ cells. The gene encodes for a protein of
      80 amino acids with unknown domain. To investigate the function of (Tex18) gene,
      we generated mice with targeted disruption of the (Tex18) gene by homologous
      recombination. Homozygous mutant males on a mixed genetic background (C57BL/6J x
      129/Sv) are fertile, while they are subfertile on the 129/Sv background, although
      mating is normal. We showed that Tex18(-/-) males are subfertile because of
      abnormal sperm morphology and reduced motility, which is called
      asthenoteratozoospermia, suggesting that (Tex18) affects sperm characteristics.
      Maturation of spermatids is unsynchronized and partially impaired in seminiferous
      tubules of Tex18(-/-) mice. Electron microscopical examination demonstrated
      abnormal structures of sperm head. In vivo experiments with sperm of Tex18(-/-)
      129/Sv mice revealed that the migration of spermatozoa from the uterus into the
      oviduct is reduced. This result is supported by the observation that sperm
      motility, as determined by the computer-assisted semen analysis system, is
      significantly affected, compared to wild-type spermatozoa. Generation of
      transgenic mice containing Tex18-EGFP fusion construct revealed a high
      transcriptional activity of (Tex18) during spermiogenesis, a process with
      morphological changes of haploid germ cells and development to mature
      spermatozoa. These results indicate that (Tex18) is expressed predominantly
      during spermatid differentiation and subfertility of the male Tex18(-/-) mice on
      the 129/Sv background is due to the differentiation arrest, abnormal sperm
      morphology and reduced sperm motility.

PMID- 17208931
TI  - Phase I/II study of preoperative cetuximab, capecitabine, and external beam
      radiotherapy in patients with rectal cancer.
AB  - BACKGROUND: To assess the safety and preliminary efficacy of concurrent
      radiotherapy, capecitabine, and cetuximab in the preoperative treatment of
      patients with rectal cancer. PATIENTS AND METHODS: Forty patients with rectal
      cancer (T3-T4, and/or N+, endorectal ultrasound) received preoperative
      radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, three
      dimensional conformal technique) in combination with cetuximab [initial dose 400
      mg/m(2) intravenous given 1 week before the beginning of radiation followed by
      250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy
      (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily,
      second dose level). RESULTS: Four and six patients were treated at the first and
      second dose level of capecitabine, respectively. No dose-limiting toxicity
      occurred. Thirty additional patients were treated with capecitabine at 825
      mg/m(2) twice daily. The most frequent grade 1/2 side-effects were acneiform rash
      (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%.
      Three grade 4 toxic effects were recorded: one myocardial infarction, one
      pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%)
      had a pathological complete response. CONCLUSIONS: Preoperative radiotherapy in
      combination with capecitabine and cetuximab is feasible with some patients
      achieving pathological downstaging.

PMID- 17208932
TI  - Searching the genomes of inbred mouse strains for incompatibilities that
      reproductively isolate their wild relatives.
AB  - Identification of the genes that underlie reproductive isolation provides
      important insights into the process of speciation. According to the Dobzhansky
      Muller model, these genes suffer disrupted interactions in hybrids due to
      independent divergence in separate populations. In hybrid populations, natural
      selection acts to remove the deleterious heterospecific combinations that cause
      these functional disruptions. When selection is strong, this process can maintain
      multilocus associations, primarily between conspecific alleles, providing a
      signature that can be used to locate incompatibilities. We applied this logic to
      populations of house mice that were formed by hybridization involving two species
      that show partial reproductive isolation, Mus domesticus and Mus musculus. Using
      molecular markers likely to be informative about species ancestry, we scanned the
      genomes of 1) classical inbred strains and 2) recombinant inbred lines for pairs
      of loci that showed extreme linkage disequilibria. By using the same set of
      markers, we identified a list of locus pairs that displayed similar patterns in
      both scans. These genomic regions may contain genes that contribute to
      reproductive isolation between M. domesticus and M. musculus. This hypothesis can
      now be tested using laboratory crosses and surveys of introgression in the wild.

PMID- 17208933
TI  - Genetic architecture of leaf ecophysiological traits in Helianthus.
AB  - We investigated quantitative trait loci (QTLs) for several leaf chemistry traits
      in early-generation hybrids between Helianthus annuus and Helianthus petiolaris,
      the parental species of the ancient diploid hybrid sunflower species Helianthus
      anomalus, Helianthus deserticola, and Helianthus paradoxus. We grew individuals
      of a second-generation backcross (BC(2)) toward H. petiolaris under optimum
      conditions in a glass house experiment. Trait values were measured once for each
      individual. In addition, genotypic data previously determined for each individual
      were employed for composite interval mapping of QTLs. We detected QTLs for leaf
      carbon concentration, leaf nitrogen concentration, leaf nitrogen per unit area,
      and photosynthetic nitrogen use efficiency. Leaf carbon isotope discrimination
      (delta(13)C) and leaf nitrogen isotopic composition (delta(15)N) were analyzed,
      but no significant QTLs were found for these traits. Interestingly, two
      neighboring loci explained a relatively large percentage of the variation in leaf
      nitrogen per unit area. This was notable because leaf nitrogen has been shown to
      strongly affect the fitness of early-generation sunflower hybrids in the H.
      anomalus habitat, and QTLs of large effect are expected to respond relatively
      quickly to selection. We speculate that the genetic architecture underlying leaf
      nitrogen may have facilitated the colonization of active desert sand dunes by H.
      anomalus.

PMID- 17208934
TI  - Evolution of duplicate gene expression in polyploid and hybrid plants.
AB  - Allopolyploidy is a prominent mode of speciation in flowering plants. On
      allopolyploidy, genomic changes can take place, including chromosomal
      rearrangement and changes in gene expression; these processes continue over
      evolutionary time. Recent studies of gene expression in polyploid and hybrid
      plants, reviewed here, have examined expression in natural polyploids and
      synthetic neopolyploids as well as in diploid and F(1) hybrids. Considerable
      changes in gene expression have been observed in allopolyploids, including up- or
      downregulation of expression in the polyploids compared with their parents,
      unequal expression of duplicated genes, and silencing of one copy. Genes in a
      variety of functional categories show altered expression, and the patterns vary
      considerably by gene. Some changes seem to be stochastic, whereas others are
      repeatable. Gene expression changes can be organ specific. Reciprocal silencing
      of duplicates in different organs has been observed, suggesting
      subfunctionalization and long-term retention of duplicates. It has become clear
      that hybridization has a much greater effect than chromosome doubling on gene
      expression in allopolyploids. Diploid and triploid F(1) hybrids can show
      alterations of expression levels compared with their parents. Parent-of-origin
      effects on gene expression have been examined, and loss of gene imprinting has
      been shown. Some gene expression changes in polyploids and hybrids can be
      correlated with phenotypic effects. Demonstrated mechanisms of gene expression
      changes include DNA methylation, histone modifications, and antisense RNA.
      Several hypotheses have been proposed for why gene expression is altered in
      allopolyploids and hybrids.

PMID- 17208935
TI  - Relation of aortic root dilatation and age in Marfan's syndrome.
AB  - AIMS: The main aim of this study was to describe the age at which pathological
      aortic root dilation occurs in patients with Marfan's syndrome (MFS). METHODS AND
      RESULTS: A total of 160 patients with MFS attending a regional cardiac centre
      were reviewed retrospectively. Dilation of the ascending aorta was diagnosed by
      comparing the maximum aortic sinus measurement with control data from the
      literature. We employed a Kaplan-Meier survival curve to estimate the age at
      which dilatation occurs. The mean age of the total group at presentation was 15.5
      years (range 1.5-40 years). Skeletal abnormalities were present in 95%. Eye
      involvement was found in 18%. In the 115/160 patients with an abnormal aortic
      root, 78/115 (68%) developed aortic root dilatation before 19 years of age. From
      the Kaplan-Meier curve, it can be estimated that about 35% of the patients have
      aortic root dilatation already at the age of 5 years and 70% before the age of 20
      years, and at least 80% by 40 years. There were 31 patients with normal aortic
      root when first seen but 24/31 (77%) developed aortic root dilatation before the
      age of 19 years and 7/31 (22.6%) after 19 years of age. Of those (seven patients)
      who developed new pathological aortic root dilatation after age 19 years, the age
      range was between 21 and 40 years with a mean of 27 years. Overall, 13 patients
      (8%) had surgery for aortic root replacement. CONCLUSION: Aortic root dilatation
      develops early in MFS and was present in 35% by the age of 5 years and 68% by 19
      years. Even though new aortic root dilation is relatively rare, it is not
      possible to safely discharge patients with MFS as about one-third of the patients
      in our series who developed new pathological aortic root dilation did so after
      the age of 19 years.

PMID- 17208936
TI  - Myocardial positive pre-ejection velocity accurately detects presence of viable
      myocardium, predicts recovery of left ventricular function and bears a prognostic
      value after surgical revascularization.
AB  - AIMS: To assess the accuracy of tissue Doppler imaging-derived myocardial
      positive pre-ejection velocity (+Vic) in detecting myocardial viability defined
      by dobutamine stress echocardiography (DSE), fluorine-18 fluorodeoxyglucose
      positron emission tomography (PET), and contrast-enhanced magnetic resonance
      imaging (MRI), and in predicting recovery of left ventricular (LV) function after
      coronary artery bypass grafting (CABG) in patients with chronic ischaemic LV
      dysfunction. METHODS AND RESULTS: +Vic in dysfunctional segments was recorded in
      54 patients treated medically and 65 patients undergoing CABG [age 67 +/- 9 year;
      LV ejection fraction (EF) 30 +/- 6%]. A good agreement was observed between +Vic
      and detection of viable myocardium at DSE, PET, and MRI (kappa = 0.76). The
      presence of +Vic in greater than or equal to five dysfunctional segments had the
      highest sensitivity (93%) and specificity (60%) to identify patients (n = 28)
      with > or =10% increase in LV EF between baseline and 6-month echocardiogram.
      During follow-up (median 333 days, interquartile range 209-490 days), 13 cardiac
      events (6 deaths, 7 hospitalizations) occurred in 24 patients with small extent
      of viable myocardium (< 5 + Vic), whereas only four hospitalizations in 39
      patients with > or =5 + Vic (54% vs. 10%; P < 0.001). CONCLUSION: The extent of
      +Vic in dysfunctional segments accurately predicts extent of viable myocardium
      and bears a clinical prognostic value in patients with ischaemic LV dysfunction
      considered for CABG.

PMID- 17208937
TI  - The making of a physician-scientist--the process has a pattern: lessons from the
      lives of Nobel laureates in medicine and physiology.
AB  - Physician-scientists are catalysts of translational research. With one foot in
      the practice of medicine and the other in research and discovery, they are
      uniquely positioned to bridge the gap between laboratory and bedside. In so
      doing, they enhance patient care, improve medical education, and increase the
      prosperity of the biomedical enterprise. Although, science has never been more
      accessible and directly applicable to human health, there is a paradoxical
      scarcity of physician-scientists. Causes of this shortage include prolonged
      training and the associated debt-load, the corporatization of medicine,
      inadequate research funding, and the complexity of a dual career. While striving
      to reduce these obstacles, we should inspire the next generation by celebrating
      the physician-scientist career track as one of Medicine's most rewarding. To this
      end, life lessons from five groups of Nobel laureates in medicine and physiology
      have been distilled, revealing the essence of the practices and philosophies that
      allowed these 'ordinary' people to achieve the extraordinary. The common threads
      in their stories guide young physician-scientists to seek out training and
      employment where a culture of research is embraced, to find a dedicated mentor
      who will help identify worthy research questions and guide their career, and to
      establish research partnerships which offer creative synergy and buffer the
      frustrations that accompany research. Further inspiration comes from those great
      researchers whose contributions shaped Medicine but did not lead to the Prize.

PMID- 17208938
TI  - Heart-type fatty acid-binding proteins (H-FABP): a reliable tool for initial risk
      stratification of pulmonary embolism?

PMID- 17208939
TI  - Mitochondrial phosphoproteome revealed by an improved IMAC method and MS/MS/MS.
AB  - IMAC in combination with mass spectrometry is a promising approach for global
      analysis of protein phosphorylation. Nevertheless this approach suffers from two
      shortcomings: inadequate efficiency of IMAC and poor fragmentation of
      phosphopeptides in the mass spectrometer. Here we report optimization of the IMAC
      procedure using (32)P-labeled tryptic peptides and development of MS/MS/MS (MS3)
      for identifying phosphopeptide sequences and phosphorylation sites. The improved
      IMAC method allowed recovery of phosphorylated tryptic peptides up to
      approximately 77% with only minor retention of unphosphorylated peptides. MS3 led
      to efficient fragmentation of the peptide backbone in phosphopeptides for
      sequence assignment. Proteomics of mitochondrial phosphoproteins using the
      resulting IMAC protocol and MS3 revealed 84 phosphorylation sites in 62 proteins,
      most of which have not been reported before. These results revealed diverse
      phosphorylation pathways involved in the regulation of mitochondrial functions.
      Integration of the optimized batchwise IMAC protocol with MS3 offers a relatively
      simple and more efficient approach for proteomics of protein phosphorylation.

PMID- 17208940
TI  - MAGE-A1, GAGE and NY-ESO-1 cancer/testis antigen expression during human gonadal
      development.
AB  - BACKGROUND: Cancer/testis antigens (CTAs) are expressed in several cancers and
      during normal adult male germ cell differentiation. Little is known about their
      role in fetal development of human germ cells. METHODS: We examined expression of
      the CTAs MAGE-A1, GAGE and NY-ESO-1 in fetal gonads by single and double
      immunohistochemical staining. RESULTS: We found that GAGE was expressed in the
      primordial germ cells of the gonadal primordium, whereas MAGE-A1 and NY-ESO-1
      were first detected in germ cells of both testis and ovary after sexual
      differentiation was initiated. The number of positive germ cells and the staining
      intensity of all three CTAs peaked during the second trimester and gradually
      decreased towards birth in both male and female germ cells. In oocytes, MAGE-A1
      expression terminated around birth, whereas NY-ESO-1 expression persisted through
      the neonatal stage and GAGE expression was maintained until adulthood. The
      population of GAGE-expressing male and female germ cells partially overlapped the
      population of OCT4-positive cells, whereas MAGE-A1 and NY-ESO-1 were clearly
      expressed only by OCT4-negative cells. CONCLUSIONS: Our results suggest that MAGE
      A1 and NY-ESO-1 are associated with highly proliferating germ cells, whereas GAGE
      proteins have a more general function in germ cells unrelated to any specific
      developmental stage. The recognition of differential cellular expression of GAGE,
      MAGE-A1, NY-ESO-1 and OCT4 may help define biologically distinct germ cell
      subpopulations.

PMID- 17208941
TI  - Adipocyte resistin mRNA levels are down-regulated by laparoscopic ovarian
      electrocautery in both obese and lean women with polycystic ovary syndrome.
AB  - BACKGROUND: The aim of this study was to investigate serum and adipocyte mRNA
      expression of resistin in lean and obese women with polycystic ovary syndrome
      (PCOS) before and 3 months after laparoscopic ovarian electrocauterization (LOE).
      METHODS: Adipose tissue obtained from 12 women with PCOS (six obese and six lean,
      body mass index > 27 kg m(-1) as threshold point) before and after LOE was
      analysed. Gene expression of resistin was measured by semi-quantitative RT-PCR.
      Ten lean, age-matched healthy women served as controls. RESULTS: Both lean and
      obese women with PCOS had significantly higher fasting and 2 h insulin and
      homeostasis model insulin resistance index (HOMA(IR)) values and lower fasting
      glucose-to-insulin ratios (G(0)/I(0)) than did the controls. The serum levels of
      glucose and insulin and HOMA(IR) were significantly decreased, and the G(0)/I(0)
      ratio was significantly increased 3 months after LOE. No difference was found in
      serum resistin levels between controls and either obese or lean women with PCOS
      before LOE, nor between PCOS patients before and after LOE. However, resistin
      mRNA expression levels in both lean and obese women with PCOS before LOE were
      significantly higher than that in controls and were decreased significantly after
      LOE back to control levels. CONCLUSION: Local resistin activity may be actively
      involved in the pathogenesis of PCOS. LOE reduces insulin resistance and down
      regulates resistin mRNA expression in lean and obese women with PCOS.

PMID- 17208942
TI  - Ultrastructural nuclear defects and increased chromosome aneuploidies in
      spermatozoa with elongated heads.
AB  - BACKGROUND: Cellular and molecular mechanisms leading to elongated sperm heads
      are not known. We have analysed the nuclear status of spermatozoa with elongated
      heads. METHODS: Fourteen men with at least 30% of spermatozoa with an elongated
      nucleus were studied and compared with five fertile men as controls. Sperm
      morphology was analysed by a quantitative ultrastructural analysis. Sperm
      chromosomal content was assessed by three-colour fluorescence in-situ
      hybridization (chromosomes X, Y, 18). Y chromosome microdeletion and karyotype
      were analysed. RESULTS: Elongated sperm head rates of the patients were 46.9% (30
      75 versus 0-2% in the control group) by light microscopy and 34.4% by electron
      microscopy. In all patients, the chromatin was poorly condensed in elongated
      sperm heads (50% of elongated nuclei). No anomalies of sperm biochemical markers
      were found. All the men showed normal karyotype (46,XY) and absence of Y
      chromosome microdeletion. Aneuploidy rates of gonosomes and chromosome 18 were
      significantly increased in patients (1.64- and 3.6-fold, P = 0.006 and 0.026,
      respectively). CONCLUSIONS: This study demonstrates that impaired chromatin
      compaction and slightly increased chromosome aneuploidies are found in
      spermatozoa with an elongated head, suggesting possible mechanisms such as
      meiotic non-disjunctions or spermiogenesis anomalies.

PMID- 17208943
TI  - Altered apoptosis and proliferation in endometrial stromal cells of women with
      adenomyosis.
AB  - BACKGROUND: The eutopic endometrium in a woman suffering from adenomyosis is
      known to be biologically different from that of healthy women. The aim of this
      study was to examine the apoptosis and proliferation of eutopic endometrium from
      women with adenomyosis. METHODS: We enrolled 23 women with adenomyosis (study
      group) and 21 without (control group). Eutopic endometrium was obtained and
      separated into single endometrial stromal cells (ESCs). ESCs were treated in
      vitro with hydrogen peroxide (H(2)O(2)) to examine their apoptosis using a
      fluorescence-activated cell sorter. Cells were also treated with estradiol
      (E(2)), medroxyprogesterone acetate, interleukin (IL)-6, lipopolysaccharide and
      interferon-gamma (IFN-gamma) to test their proliferation using a non-radioactive
      cell proliferation assay. RESULTS: The percentage of annexin V ( + )/7-amino
      actinomycin D ( + ) ESCs was much lower in women with adenomyosis after 24 h
      culture with and without H(2)O(2) treatment when compared with the control group.
      ESCs of adenomyosis proliferated more rapidly than those of the control group,
      whether they were cultured alone or were treated with E(2), MPA, IL-6 or IFN
      gamma. The immunocytochemical Ki-67 labelling index was much more prominent in
      adenomyotic ESCs than that of the control group (7.7% versus 1.1%, P < 0.001).
      CONCLUSIONS: Altered apoptosis and proliferation of eutopic endometrium possibly
      elucidate some aspects of the pathophysiology of adenomyosis. A high Ki-67
      labelling index in immunocytochemistry might be a potential indicator in
      predicting the occurrence of adenomyosis.

PMID- 17208944
TI  - Sperm quality and pregnancy rate after COX-2 inhibitor therapy of infertile males
      with abacterial leukocytospermia.
AB  - BACKGROUND: Leukocytes are a frequent finding in seminal plasma of infertile
      males with abacterial inflammation. We evaluated the effects of treatment with
      rofecoxib, a cyclooxygenase-2 inhibitor, on sperm quality and pregnancy rate
      after intrauterine insemination (IUI) or monitored intercourse. METHODS: We
      selected 47 infertile patients referred to our sterility centre for semen
      analysis. Sperm evaluation was performed by light microscopy with Papanicolau and
      eosin staining, before and 1 month after therapy. Swim-up selection was carried
      out in two steps. Starting 6-8 weeks after the end of therapy, couples underwent
      different procedures of assisted fertilization according to their semen
      parameters. RESULTS: Semen analysis 30 days after the end of therapy showed a
      significant reduction in leukocyte concentrations with respect to baseline, an
      improvement of sperm motility and morphology, particularly the presence and shape
      of the acrosomal complex and tail structure. After monitored intercourse and IUI,
      pregnancy rate was 15.8 and 11.3%, respectively. CONCLUSIONS: Our results suggest
      that a decrease in leukocytospermia after rofecoxib therapy was associated with
      recovery of all seminal characteristics in basal and swim-up selected samples.
      This general improvement could justify the positive outcome of ART after anti
      inflammatory therapy.

PMID- 17208945
TI  - Cells with haematopoietic stem cell phenotype in adult human endometrium:
      relevance to infertility?
AB  - BACKGROUND: Uterine lymphoid cell repertoires are specialized in order to meet
      the twin demands of successful pregnancy and local immunosurveillance. The
      possibility that some of these populations might differentiate locally from
      progenitor cells has been proposed. METHODS: Endometrial tissue from women with a
      history of infertility as well as fertile controls was examined for
      haematopoietic stem cells (HSCs) and lymphoid progenitors using three-colour flow
      cytometry. RESULTS: Significant populations of phenotypic HSCs (CD34+ CD45+ )
      were detected in all samples, a high proportion of which co-expressed the
      differentiation marker CD45RA (45.7%), indicating ongoing differentiation. Almost
      30% of uterine HSCs co-expressed CD56 and 44% co-expressed CD7, suggesting the
      presence of lymphoid progenitors. Small proportions expressed CD127 and CD122,
      receptors for interleukin (IL)-7 and IL-15, respectively. HSC numbers were
      similar in the endometrial samples from fertile and infertile women. However, the
      proportion co-expressing the natural killer (NK) antigen CD56 was significantly
      increased compared with HSCs found in the endometrium of fertile controls (P =
      0.002). CONCLUSIONS: This is the first demonstration of cells with an HSC
      phenotype in the human endometrium, and increased proportions of NK progenitors
      in endometrium of women with infertility suggests a dysregulation of this pathway
      that may contribute to infertility.

PMID- 17208946
TI  - Peritoneal tissue-oxygen tension during a carbon dioxide pneumoperitoneum in a
      mouse laparoscopic model with controlled respiratory support.
AB  - BACKGROUND: Previous animal studies suggested that the peritoneal environment
      during a carbon dioxide (CO(2)) pneumoperitoneum is hypoxic and that this may
      contribute to the formation of intra-abdominal adhesions or the growth of
      malignant cells. There is no study, however, that investigates the relationship
      between anaesthesia, ventilation and the laparoscopic peritoneal environment to
      the development of hypoxia. The objective of this study is to monitor the
      peritoneal tissue-oxygen tension (PitO(2)) under various conditions including
      anaesthesia alone, during a CO(2) pneumoperitoneum at both low and high
      intraperitoneal pressure (IPP), and laparotomy, in animal models with controlled
      respiratory support (CRS). METHODS: C57BL6 mice were divided into eight groups (n
      = 5) consisting of anaesthesia alone or with CO(2) pneumoperitoneum at low (2
      mmHg) or high (8 mmHg) IPP or undergoing laparotomy. Groups were further
      subdivided into those with or without CRS with endotracheal intubation and
      mechanical ventilation. Over the course of the 1 h procedure, PitO(2) was
      continuously monitored. RESULTS: Protocol 1. The PitO(2) levels (104.2 +/- 7.8
      mmHg, mean +/- SEM) in non-injured peritoneum during a CO(2) pneumoperitoneum at
      a low IPP were elevated approximately 2-fold over the levels during laparotomy
      (49.8 +/- 15.0 mmHg) in ventilated mice. Protocol 2. After insufflation with
      CO(2), the PitO(2) was immediately elevated and maintained at a higher level.
      Following laparotomy, it decreased immediately. This elevation was not seen with
      air insufflation. CONCLUSION: In mice, a significant elevation in PitO(2) occurs
      during a CO(2) pneumoperitoneum at low IPP with CRS.

PMID- 17208947
TI  - Loss of functional ELOVL4 depletes very long-chain fatty acids (> or =C28) and
      the unique omega-O-acylceramides in skin leading to neonatal death.
AB  - Mutations in elongation of very long-chain fatty acid-4 (ELOVL4) are associated
      with autosomal dominant Stargardt-like macular degeneration (STGD3), with a five
      base-pair (5 bp) deletion mutation resulting in the loss of 51 carboxy-terminal
      amino acids and truncation of the protein. In addition to the retina, Elovl4 is
      expressed in a limited number of mammalian tissues, including skin, with unknown
      function(s). We generated a knock-in mouse model with the 5-bp deletion in the
      Elovl4 gene. As anticipated, mice carrying this mutation in the heterozygous
      state (Elovl4(+/del)) exhibit progressive photoreceptor degeneration.
      Unexpectedly, homozygous mice (Elovl4(del/del)) display scaly, wrinkled skin,
      have severely compromised epidermal permeability barrier function, and die within
      a few hours after birth. Histopathological evaluation of the Elovl4(del/del) pups
      revealed no apparent abnormality(ies) in vital internal organs. However, skin
      histology showed an abnormally-compacted outer epidermis [stratum corneum (SC)],
      while electron microscopy revealed deficient epidermal lamellar body contents,
      and lack of normal SC lamellar membranes that are essential for permeability
      barrier function. Lipid analyses of epidermis from Elovl4(del/del) mice revealed
      a global decrease in very long-chain fatty acids (VLFAs) (i.e., carbon chain > or
      =C28) in both the ceramide/glucosylceramide and the free fatty-acid fractions.
      Strikingly, Elovl4(del/del) skin was devoid of the epidermal-unique omega-O
      acylceramides, that are key hydrophobic components of the extracellular lamellar
      membranes in mammalian SC. These findings demonstrate that ELOVL4 is required for
      generating VLFA critical for epidermal barrier function, and that the lack of
      epidermal omega-O-acylceramides is incompatible with survival in a desiccating
      environment.

PMID- 17208948
TI  - The impact of lifestyle factors on reproductive performance in the general
      population and those undergoing infertility treatment: a review.
AB  - This evidence-based review focuses on the impact of potentially modifiable, non
      communicable lifestyle factors on reproductive performance in the general
      population and the infertile population undergoing assisted reproductive
      technology (ART) treatment. The impact of several lifestyle factors including;
      age, weight, smoking, diet, exercise, psychological stress, caffeine consumption,
      alcohol consumption and exposure to environmental pollutants are included in the
      review. The databases of Medline, PubMed and Cinahl were searched to identify
      relevant publications. There is strong evidence that age, weight and smoking
      impact on general health and adversely on reproductive performance. However there
      is a need for further research focusing specifically on the relationship between
      diet and various levels of exercise on reproductive performance. There are
      several other factors such as psychological stress, caffeine consumption, alcohol
      consumption and exposure to environmental pollutants that have been implicated
      but the evidence is equivocal. It is concluded that lifestyle modification can
      assist couples to conceive spontaneously or optimize their chances of conception
      with ART treatment.

PMID- 17208949
TI  - Why does ovarian surgery in PCOS help? Insight into the endocrine implications of
      ovarian surgery for ovulation induction in polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a complex disorder with heterogeneity of
      clinical and endocrine features. Ovarian surgery for ovulation induction has been
      used in the management of clomiphene citrate-resistant anovulatory women with
      PCOS. Various types of ovarian surgery have been employed (wedge resection,
      electrocautery, laser vaporization, multiple ovarian biopsies and others) and all
      procedures result in an altered endocrine profile after surgery. The mechanism
      behind the reversal of endocrinological dysfunction in PCOS after ovarian surgery
      remains incompletely understood. This review scans the literature systematically
      to identify the endocrine changes after ovarian surgery in PCOS, in order to
      glean some knowledge of the mechanism involved. After ovarian surgery in PCOS, a
      rapid reduction in serum levels of all ovarian hormones is seen, in combination
      with increased serum levels of pituitary hormones. Folliculogenesis is then
      initiated and ovarian hormone production increases, synchronically with a
      reduction of pituitary hormones. Continuation of follicle growth in subsequent
      cycles after ovarian surgery occurs in an environment with less androgens and
      lower LH and FSH levels compared with pretreatment levels. The endocrine changes
      found after ovarian surgery in PCOS women seem to be governed by the ovaries
      themselves. Rapid reduced secretion of all ovarian hormones restores feedback to
      the hypothalamus and pituitary, resulting in appropriate gonadotrophin secretion.
      Initiation of follicular development seems to be induced by increasing FSH levels
      following a reduction of the follicle excess and (intra-ovarian) androgen levels.
      Additionally, anti-Mullerian hormone and gonadotrophin surge attenuating factor
      probably have a role in the endocrine changes.

PMID- 17208950
TI  - Altered protamine expression and diminished spermatogenesis: what is the link?
AB  - During the elongating spermatid stage of spermiogenesis, human sperm chromatin
      undergoes a complex transition in which histones are extensively replaced by
      protamines in a carefully regulated transition including histone modifications
      and intermediate and temporary replacement of the histones by sperm-specific
      transition proteins. The replacement of most histones by protamines 1 and 2
      facilitates a high order of chromatin packaging necessary for normal sperm
      function and may also be necessary for DNA silencing and imprinting changes
      within the sperm cell. Protamines 1 and 2 are usually expressed in nearly equal
      quantities, but elevated or diminished protamine 1/protamine 2 ratios are
      observed in some infertile men and is often associated with severe
      spermatogenesis defects. Human and animal studies demonstrate that expression of
      the protamine proteins is uniquely regulated by transcription/translation
      factors, including storage of the mRNA in ribonucleoprotein (RNP) particles
      composed of the mRNA, transcription factors and a kinesin molecule necessary for
      transport of the RNP to the cytoplasm and removal of transcriptional activators
      from the nucleus. Recent studies indicate that most patients with abnormal
      protamine protein levels have elevated levels of protamine transcript in the
      mature sperm cell, indicating a possible defect in transcription or translation.
      The regulation of protamine expression is unique and includes several possible
      mechanisms which may be responsible for dysregulation of protamine expression and
      concurrent broad spectrum defects in spermatogenesis. We suggest two hypotheses:
      (i) that abnormal protamine expression is indicative of a generalized defect in
      mRNA storage and/or translation which affects other mRNA transcripts or (ii) that
      protamines may act as a checkpoint of spermatogenesis.

PMID- 17208951
TI  - DHEA therapy for women: effect on sexual function and wellbeing.
AB  - DHEA is increasingly available commercially as a supplement aimed at improving
      libido and wellbeing in postmenopausal women. However there is scant evidence to
      support the use of DHEA for this purpose, and safety data for DHEA therapy are
      lacking. Dehydroepiandrosterone (DHEA) and its sulphate DHEAS are the most
      abundant circulating sex steroid hormones in women, providing a large precursor
      reservoir for the intracellular production of androgens and oestrogens in non
      reproductive tissues. Levels of DHEA and DHEAS decline with age. It has been
      proposed that restoring the circulating levels of these steroids to those found
      in young people may have anti-ageing effects and improve wellbeing and sexual
      function. However this is not supported by the published literature. We have
      reviewed the physiology of DHEA and DHEAS in women and the published literature
      pertaining to the use of DHEA therapy for libido and wellbeing in postmenopausal
      women. The literature was searched using Medline (Ovid) and Pub-Med for original
      studies. Overall, the interpretation of data from randomised controlled trials
      conducted in well women is limited by inadequate sample size and short treatment
      durations with inconsistent results for the outcomes of libido and wellbeing.
      Studies of DHEA in women with adrenal insufficiency, although indicating
      potential improvements in mood and libido, are also limited by their short
      treatment phase durations. In addition safety data for DHEA therapy are lacking.
      The potential value of DHEA therapy for women still requires exploration in
      adequately powered well-designed randomised placebo-controlled trials. The
      studies of DHEA therapy in women with adrenal insufficiency suggest that this
      group is the most likely to derive health benefits from DHEA supplementation.

PMID- 17208953
TI  - Health care provision for illegal migrants: may health policy make a difference?
AB  - Illegal migrants in Europe are, generally, only entitled to emergency care and
      services for children and pregnant women. In 2002 legal changes in Spain made
      accessible medical cards and free medical care for illegal migrants in similar
      terms than the legal migrants or the Spanish population. We interviewed 380
      migrants to assess whether there were differences on health services utilization
      by legal status. We did not find differences in the utilization of health
      services when ill between legal and illegal migrants. However, a significantly
      lower utilization of health services was associated with less education (RP =
      0.4; 95% CI: 0.2-0.9).

PMID- 17208952
TI  - A multifactorial fall prevention programme in the community-dwelling aged:
      predictors of adherence.
AB  - BACKGROUND: Overall adherence rates have usually been reported in fall prevention
      studies, but predictors of adherence have rarely been described. The aim of this
      study was to determine the adherence rates and the predictors of adherence in
      four key activities of a multifactorial fall prevention trial. METHODS: This
      study is part of a multifactorial fall prevention programme implemented among the
      65-year-old or older community-dwelling aged who had fallen at least once during
      the previous 12 months. Subjects (n = 591) were randomly assigned to an intensive
      prevention programme or to a counselling group. Four key activities of prevention
      programme included physical exercise in small groups, psychosocial group
      activities, lectures and home exercises. Associations between adherence rates and
      potential predictors were analysed using cumulative logistic regression. RESULTS:
      The mean adherence rate was 58% in the physical exercise groups, 25% in the
      psychosocial groups and 33% in lectures. Subjects performed home-exercises on
      average 11 times per month. In multivariate analyses, infrequent feelings of
      loneliness, low self-perceived probability of falling at home and good physical
      functional abilities were significant predictors of active physical exercise
      group adherence. Good physical and cognitive functional abilities predicted
      active psychosocial group adherence. Female gender and good physical and
      cognitive functional abilities predicted more active lecture adherence.
      CONCLUSION: Persons with the poorest physical, cognitive and psychological
      functional abilities representing the part of the population at highest risk of
      falling do not seem reachable in multifactorial risk-based intervention.

PMID- 17208954
TI  - The effects of a three-year smoking prevention programme in secondary schools in
      Helsinki.
AB  - BACKGROUND: This study evaluates the effects of a 3-year smoking prevention
      programme in secondary schools in Helsinki. The study is part of the European
      Smoking prevention Framework Approach (ESFA), in which Denmark, Finland, the
      Netherlands, Portugal, Spain and the UK participated. METHODS: A total of 27
      secondary schools in Finland participated in the programme (n = 1821). Schools
      were randomised into experimental (13) and control groups (14). The programme
      included 14 information lessons about smoking and refusal skills training. The 3
      year smoking prevention programme was also integrated into the standard
      curriculum. The community-element of the programme included parents, parish
      confirmation camps and dentists. The schools in the experimental group received
      the prevention programme and the schools in the control group received the
      standard health education curriculum. RESULTS: Among baseline never smokers
      (60.8%), the programme had a significant effect on the onset of weekly smoking in
      the experimental group [OR = 0.63 (0.45-0.90) P = 0.009] when compared with the
      control group. Being female, doing poorly at school, having parents and best
      friends who smoke and more pocket money to spend compared with others were
      associated with an increased likelihood of daily and weekly smoking onset. These
      predictors did not have an interaction effect with the experimental condition.
      CONCLUSION: This study shows that a school- and community-based smoking
      prevention programme can prevent smoking onset among adolescents.

PMID- 17208955
TI  - Clarithromycin monotherapy-induced delirium.

PMID- 17208956
TI  - Isolation of a regulatory gene of anthocyanin biosynthesis in tuberous roots of
      purple-fleshed sweet potato.
AB  - Many transcriptional factors harboring the R2R3-MYB domain, basic helix-loop
      helix domain, or WD40 repeats have been identified in various plant species as
      regulators of flavonoid biosynthesis in flowers, seeds, and fruits. However, the
      regulatory elements of flavonoid biosynthesis in underground organs have not yet
      been elucidated. We isolated the novel MYB genes IbMYB1 and IbMYB2s from purple
      fleshed sweet potato (Ipomoea batatas L. Lam. cv Ayamurasaki). IbMYB1 was
      predominantly expressed in the purple flesh of tuberous roots but was not
      detected (or only scarcely) in other anthocyanin-containing tissues such as
      nontuberous roots, stems, leaves, or flowers. IbMYB1 was also expressed in the
      tuberous roots of other purple-fleshed cultivars but not in those of orange-,
      yellow-, or white-fleshed cultivars. Although the orange- or yellow-fleshed
      cultivars contained anthocyanins in the skins of their tuberous roots, we could
      not detect IbMYB1 transcripts in these tissues. These results suggest that IbMYB1
      controls anthocyanin biosynthesis specifically in the flesh of tuberous roots.
      The results of transient and stable transformation experiments indicated that
      expression of IbMYB1 alone was sufficient for induction of all structural
      anthocyanin genes and anthocyanin accumulation in the flesh of tuberous roots, as
      well as in heterologous tissues or heterologous plant species.

PMID- 17208957
TI  - Cold nights impair leaf growth and cell cycle progression in maize through
      transcriptional changes of cell cycle genes.
AB  - Low temperature inhibits the growth of maize (Zea mays) seedlings and limits
      yield under field conditions. To study the mechanism of cold-induced growth
      retardation, we exposed maize B73 seedlings to low night temperature (25 degrees
      C /4 degrees C, day/night) from germination until the completion of leaf 4
      expansion. This treatment resulted in a 20% reduction in final leaf size compared
      to control conditions (25 degrees C/18 degrees C, day/night). A kinematic
      analysis of leaf growth rates in control and cold-treated leaves during daytime
      showed that cold nights affected both cell cycle time (+65%) and cell production
      (-22%). In contrast, the size of mature epidermal cells was unaffected. To
      analyze the effect on cell cycle progression at the molecular level, we
      identified through a bioinformatics approach a set of 43 cell cycle genes and
      analyzed their expression in proliferating, expanding, and mature cells of leaves
      exposed to either control or cold nights. This analysis showed that: (1) the
      majority of cell cycle genes had a consistent proliferation-specific expression
      pattern; and (2) the increased cell cycle time in the basal meristem of leaves
      exposed to cold nights was associated with differential expression of cell cycle
      inhibitors and with the concomitant down-regulation of positive regulators of
      cell division.

PMID- 17208958
TI  - Major proteome variations associated with cherry tomato pericarp development and
      ripening.
AB  - Tomato (Solanum lycopersicum) is a model plant for studying fleshy fruit
      development. Several genetic and molecular approaches have been developed to
      increase our knowledge about the physiological basis of fruit growth, but very
      few data are yet available at the proteomic level. The main stages of fruit
      development were first determined through the dynamics of fruit diameter and
      pericarp cell number. Then, total proteins were extracted from pericarp tissue at
      six relevant developmental stages and separated by two-dimensional gel
      electrophoresis. Protein patterns were markedly different between stages.
      Proteins showing major variations were monitored. We identified 90 of 1,791 well
      resolved spots either by matrix-assisted laser-desorption ionization time-of
      flight peptide mass fingerprinting or liquid chromatography-mass spectrometry
      sequencing and expressed sequence tag database searching. Clustered correlation
      analysis results pointed out groups of proteins with similar expression profiles
      during fruit development. In young fruit, spots linked to amino acid metabolism
      or protein synthesis were mainly expressed during the cell division stage and
      down-regulated later. Some spots linked to cell division processes could be
      identified. During the cell expansion phase, spots linked to photosynthesis and
      proteins linked to cell wall formation transiently increased. In contrast, the
      major part of the spots related to C compounds and carbohydrate metabolism or
      oxidative processes were up-regulated during fruit development, showing an
      increase in spot intensity during development and maximal abundance in mature
      fruit. This was also the case for spots linked to stress responses and fruit
      senescence. We discuss protein variations, taking into account their potential
      role during fruit growth and comparing our results with already known variations
      at mRNA and metabolite-profiling levels.

PMID- 17208959
TI  - Characterization of a selenate-resistant Arabidopsis mutant. Root growth as a
      potential target for selenate toxicity.
AB  - Screening an Arabidopsis (Arabidopsis thaliana) T-DNA mutant library for selenate
      resistance enabled us to isolate a selenate-resistant mutant line (sel1-11).
      Molecular and genetic characterization showed that the mutant contained a lesion
      in the SULTR1;2 gene that encodes a high affinity root sulfate transporter. We
      showed that SULTR1;2 is the only gene among 13 mutated genes of the Arabidopsis
      sulfate transporter family whose mutation conferred selenate resistance to
      Arabidopsis. The selenate resistance phenotype of the sel1-11 mutant was mirrored
      by an 8-fold increase of root growth in the presence of selenate as shown by the
      calculated lethal concentration values. The impairment of SULTR1;2 activity in
      sel1-11 resulted in a reduced (35)S-sulfate uptake capacity by both roots and
      calli and a reduced sulfate and selenate content in root, shoot, and calli.
      Comparing sulfate-to-selenate ratios instead of absolute sulfate and selenate
      contents in roots and shoots enabled us to gain better insight into the mechanism
      of selenate toxicity in Arabidopsis. Roots of the sel1-11 mutant line showed a
      higher sulfate to selenate ratio than that of wild-type roots, while there were
      no significant differences in sulfate to selenate ratios in shoots of wild-type
      and mutant lines. These results indicated that the mechanism that confers the
      selenate resistance phenotype to the sel1-11 line takes place rather in the
      roots. It might be in part the result of a lower selenate uptake and of a
      protective effect of sulfate against the toxic effects of selenate on root
      growth. These results revealed in plants a central and specific role of the
      transporter SULTR1;2 in selenate sensitivity; they further suggested that root
      growth and potentially the root tip activity might be a specific target of
      selenate toxicity in Arabidopsis.

PMID- 17208960
TI  - Abscisic acid and stress signals induce Viviparous1 expression in seed and
      vegetative tissues of maize.
AB  - Viviparous1 (Vp1) encodes a B3 domain-containing transcription factor that is a
      key regulator of seed maturation in maize (Zea mays). However, the mechanisms of
      Vp1 regulation are not well understood. To examine physiological factors that may
      regulate Vp1 expression, transcript levels were monitored in maturing embryos
      placed in culture under different conditions. Expression of Vp1 decreased after
      culture in hormone-free medium, but was induced by salinity or osmotic stress.
      Application of exogenous abscisic acid (ABA) also induced transcript levels
      within 1 h in a dose-dependent manner. The Vp1 promoter fused to beta
      glucuronidase or green fluorescent protein reproduced the endogenous Vp1
      expression patterns in transgenic maize plants and also revealed previously
      unknown expression domains of Vp1. The Vp1 promoter is active in the embryo and
      aleurone cells of developing seeds and, upon drought stress, was also found in
      phloem cells of vegetative tissues, including cobs, leaves, and stems. Sequence
      analysis of the Vp1 promoter identified a potential ABA-responsive complex,
      consisting of an ACGT-containing ABA response element (ABRE) and a coupling
      element 1-like motif. Electrophoretic mobility shift assay confirmed that the
      ABRE and putative coupling element 1 components specifically bound proteins in
      embryo nuclear protein extracts. Treatment of embryos in hormone-free Murashige
      and Skoog medium blocked the ABRE-protein interaction, whereas exogenous ABA or
      mannitol treatment restored this interaction. Our data support a model for a VP1
      dependent positive feedback mechanism regulating Vp1 expression during seed
      maturation.

PMID- 17208961
TI  - Phytochelatin synthases of the model legume Lotus japonicus. A small multigene
      family with differential response to cadmium and alternatively spliced variants.
AB  - The biosynthesis of phytochelatins and homophytochelatins has been studied in
      nodulated plants of the model legume Lotus (Lotus japonicus). In the first 6 to
      24 h of treatment with cadmium (Cd), roots started to synthesize elevated amounts
      of both polypeptides, with a concomitant increase of glutathione and a decrease
      of homoglutathione, indicating the presence of active phytochelatin synthase
      (PCS) genes. Screening of transformation-competent artificial chromosome
      libraries allowed identification of a cluster of three genes, LjPCS1, LjPCS2, and
      LjPCS3, which were mapped at 69.0 cM on chromosome 1. The genes differ in exon
      intron composition and responsiveness to Cd. Gene structures and phylogenetic
      analysis of the three protein products, LjPCS1-8R, LjPCS2-7N, and LjPCS3-7N, are
      consistent with two sequential gene duplication events during evolution of
      vascular plants. Two sites for alternative splicing in the primary transcripts
      were identified. One of them, involving intron 2 of the LjPCS2 gene, was
      confirmed by the finding of the two predicted mRNAs, encoding LjPCS2-7R in roots
      and LjPCS2-7N in nodules. The amino acid sequences of LjPCS2-7R (or LjPCS2-7N)
      and LjPCS3-7N share 90% identity, but have only 43% to 59% identity with respect
      to the typical PCS1 enzymes of Lotus and other plants. The unusual LjPCS2-7N and
      LjPCS3-7N proteins conferred Cd tolerance when expressed in yeast (Saccharomyces
      cerevisiae) cells, whereas the alternatively spliced form, LjPCS2-7R, differing
      only in a five-amino acid motif (GRKWK) did not. These results unveil complex
      regulatory mechanisms of PCS expression in legume tissues in response to heavy
      metals and probably to other developmental and environmental factors.

PMID- 17208962
TI  - Conservation, convergence, and divergence of light-responsive, circadian
      regulated, and tissue-specific expression patterns during evolution of the
      Arabidopsis GATA gene family.
AB  - In vitro analyses of plant GATA transcription factors have implicated some
      proteins in light-mediated and circadian-regulated gene expression, and, more
      recently, the analysis of mutants has uncovered further diverse roles for plant
      GATA factors. To facilitate function discovery for the 29 GATA genes in
      Arabidopsis (Arabidopsis thaliana), we have experimentally verified gene
      structures and determined expression patterns of all family members across adult
      tissues and suspension cell cultures, as well as in response to light and signals
      from the circadian clock. These analyses have identified two genes that are
      strongly developmentally light regulated, expressed predominantly in
      photosynthetic tissue, and with transcript abundance peaking before dawn. In
      contrast, several GATA factor genes are light down-regulated. The products of
      these light-regulated genes are candidates for those proteins previously
      implicated in light-regulated transcription. Coexpression of these genes with
      well-characterized light-responsive transcripts across a large microarray data
      set supports these predictions. Other genes show additional tissue-specific
      expression patterns suggesting novel and unpredicted roles. Genome-wide analysis
      using coexpression scatter plots for paralogous gene pairs reveals unexpected
      differences in cocorrelated gene expression profiles. Clustering the Arabidopsis
      GATA factor gene family by similarity of expression patterns reveals that genes
      of recent descent do not uniformly show conserved current expression profiles,
      yet some genes showing more distant evolutionary origins have acquired common
      expression patterns. In addition to defining developmental and environmental
      dynamics of GATA transcript abundance, these analyses offer new insights into the
      evolution of gene expression profiles following gene duplication events.

PMID- 17208964
TI  - Voltage-clamp fluorometry in the local environment of the C255-C511 disulfide
      bridge of the Na+/glucose cotransporter.
AB  - We recently identified a functionally important disulfide bridge between C255 and
      C511 of the human Na+/glucose cotransporter SGLT1. In this study, voltage-clamp
      fluorometry was used to characterize the fluorescence of four different dyes
      attached to C255 and C511 under various ionic and substrate/inhibitor conditions.
      State-dependent fluorescence changes (DeltaF) were observed when TMR5M or TMR6M
      dyes were attached to C255 and C511 or when Alexa488 was bound to C511. TMR5M
      C511 was extremely sensitive to membrane potential (Vm) and to external Na+ and
      alphaMG (a nonmetabolizable glucose analog) concentrations. A progressive
      increase in alphaMG concentration drastically changed the maximal voltage
      dependent DeltaF and produced a positive shift in the midpoint of the DeltaF-Vm
      curve. By determining specific fluorescence intensity for each state of the
      cotransporter, our steady-state fluorescence data could be reproduced using the
      rate constants previously proposed for a five-state kinetic model exclusively
      derived from electrophysiological measurements. Our results bring an independent
      support to the proposed kinetic model and show that the binding of alphaMG
      substrate significantly modifies the environment of C255 and C511.

PMID- 17208963
TI  - The grapevine transcription factor VvMYBPA1 regulates proanthocyanidin synthesis
      during fruit development.
AB  - Proanthocyanidins (PAs; or condensed tannins) can protect plants against
      herbivores, contribute to the taste of many fruits, and act as dietary
      antioxidants beneficial for human health. We have previously shown that in
      grapevine (Vitis vinifera) PA synthesis involves both leucoanthocyanidin
      reductase (LAR) and anthocyanidin reductase (ANR). Here we report the
      characterization of a grapevine MYB transcription factor VvMYBPA1, which controls
      expression of PA pathway genes including both LAR and ANR. Expression of VvMYBPA1
      in grape berries correlated with PA accumulation during early berry development
      and in seeds. In a transient assay, VvMYBPA1 activated the promoters of LAR and
      ANR, as well as the promoters of several of the general flavonoid pathway genes.
      VvMYBPA1 did not activate the promoter of VvUFGT, which encodes the anthocyanin
      specific enzyme UDP-glucose:flavonoid-3-O-glucosyltransferase, suggesting
      VvMYBPA1 is specific to regulation of PA biosynthesis in grapes. The Arabidopsis
      (Arabidopsis thaliana) MYB transcription factor TRANSPARENT TESTA2 (TT2)
      regulates PA synthesis in the seed coat of Arabidopsis. By complementing the PA
      deficient seed phenotype of the Arabidopsis tt2 mutant with VvMYBPA1, we
      confirmed the function of VvMYBPA1 as a transcriptional regulator of PA
      synthesis. In contrast to ectopic expression of TT2 in Arabidopsis, constitutive
      expression of VvMYBPA1 resulted in accumulation of PAs in cotyledons, vegetative
      meristems, leaf hairs, and roots in some of the transgenic seedlings. To our
      knowledge, this is the first report of a MYB factor that controls genes of the PA
      pathway in fruit, including both LAR and ANR, and this single MYB factor can
      induce ectopic PA accumulation in Arabidopsis.

PMID- 17208965
TI  - Effects of adaptation in maintaining high sensitivity over a wide range of
      backgrounds for Escherichia coli chemotaxis.
AB  - An allosteric model is developed to study the cooperative kinase response of wild
      type (wt) Escherichia coli cells to the chemoattractant MeAsp in different
      ambient MeAsp concentrations. The model, together with wt dose response data,
      reveals the underlying mechanism for E. coli's ability to maintain high
      sensitivity over a wide range of backgrounds. We find: 1), Adaptation tunes the
      system to the steepest part of the dose response curve, where the sensitivity to
      a given type of stimulus is amplified by the number of corresponding receptors in
      the (mixed) functional receptor complex. A lower bound on the number of Tar
      receptor dimers (Na) in the complex Na>approximately 6 is obtained from the
      measured sensitivity. 2), Accurate adaptation synchronizes the kinase activities
      from different (uncoupled) receptor complexes in a single cell and is crucial in
      maintaining the high Hill coefficient in the (population averaged) kinase
      response curve. 3), The wide dynamic range of the high sensitivity can be
      explained in our model by either having a very small ratio between ligand
      dissociation constants of the inactive and the active receptors C=0.006, Na=6,
      and a (methylation level independent) dissociation constant for the inactive Tar
      receptor K=18.2 microM or by having K and/or Na increase with receptor
      methylation level together with a larger value of C>0.01. Specific experiments
      are suggested to distinguish these two scenarios. 4), The receptor occupancy in a
      wt cell should also adapt and exhibit a slow (approximately logarithmic)
      dependence on the ligand concentration in the adapted state; this general
      prediction can be tested experimentally to verify/falsify our model.

PMID- 17208966
TI  - Extending Iterative Protein Redesign and Optimization (IPRO) in protein library
      design for ligand specificity.
AB  - In this article we extend the Iterative Protein Redesign and Optimization (IPRO)
      framework for the design of protein libraries with targeted ligand specificity.
      Mutations that minimize the binding energy with the desired ligand are
      identified. At the same time explicit constraints are introduced that maintain
      the binding energy for all decoy ligands above a threshold necessary for
      successful binding. The proposed framework is demonstrated by computationally
      altering the effector binding specificity of the bacterial transcriptional
      regulatory protein AraC, belonging to the AraC/XylS family of transcriptional
      regulators for different unnatural ligands. The obtained results demonstrate the
      importance of systematically suppressing the binding energy for competing
      ligands. Pinpointing a small set of mutations within the binding pocket greatly
      improves the difference in binding energies between targeted and decoy ligands,
      even when they are very similar.

PMID- 17208967
TI  - Molecular analysis of TCR and peptide/MHC interaction using P18-I10-derived
      peptides with a single D-amino acid substitution.
AB  - For the structural analysis of T-cell receptor (TCR) and peptide/MHC interaction,
      a series of peptides with a single amino acid substitution by a corresponding D
      amino acid, having the same weight, size, and charge, within P18-I10 (aa318-327:
      RGPGRAFVTI), an immunodominant epitope of HIV-1 IIIB envelope glycoprotein,
      restricted by the H-2Dd class I MHC molecule, has been synthesized. Using those
      peptides, we have observed that the replacement at positions 324F, 325V, 326T,
      and 327I with each corresponding D-amino acid induced marked reduction of the
      potency to sensitize targets for P18-I10-specific murine CD8+ cytotoxic T
      lymphocytes (CTLs), LINE-IIIB, recognition. To analyze further the role of amino
      acid at position 325, the most critical site for determining epitope specificity,
      we have developed a CTL line [LINE-IIIB(325D)] and its offspring clones specific
      for the epitope I-10(325v) having a D-valine (v) at position 325. Taking
      advantage of two distinct sets of CD8+ CTLs restricted by the same Dd, three
      dimensional structural analysis on TCR and peptide/MHC complexes by molecular
      modeling was performed, which indicates that the critical amino acids within the
      TCRs for interacting with 325V or 325v appear to belong to the complementarity
      determining region 1 but not to the complementarity-determining region 3 of Vbeta
      chain.

PMID- 17208968
TI  - Targeting AMPA receptor gating processes with allosteric modulators and
      mutations.
AB  - Allosteric modulators and mutations that slow AMPAR desensitization have
      additional effects on deactivation and agonist potency. We investigated whether
      these are independent actions or the natural consequence of slowing
      desensitization. Effects of cyclothiazide (CTZ), trichlormethiazide (TCM), and
      CX614 were compared at wild-type GluR1 and "nondesensitizing" GluR1-L497Y mutant
      receptors by patch-clamp recording with ultrafast perfusion. CTZ, TCM, or L/Y
      mutation all essentially blocked GluR1 desensitization; however, the effects of
      L/Y mutation on deactivation and glutamate EC50 were three to five times greater
      than for modulators. CTZ and TCM further slowed desensitization of L/Y mutant
      receptors but paradoxically accelerated deactivation and increased agonist EC50.
      Results indicate that CTZ and TCM target deactivation and agonist potency
      independently of desensitization, most likely by modifying agonist dissociation
      (koff). Conversely, CX614 slowed desensitization and deactivation without
      affecting EC50 in both wild-type and L/Y receptors. The S750Q or combined L497Y
      S750Q mutations abolished all CTZ and TCM actions without disrupting CX614
      activity. Notably, the S/Q mutation also restored L/Y deactivation and EC50 to
      wild-type levels without restoring desensitization, further demonstrating that
      desensitization can be modulated independently of deactivation and EC50 by
      mutagenesis and possibly by allosteric modulators.

PMID- 17208969
TI  - Dynamics of lysozyme structure network: probing the process of unfolding.
AB  - Recently we showed that the three-dimensional structure of proteins can be
      investigated from a network perspective, where the amino acid residues represent
      the nodes in the network and the noncovalent interactions between them are
      considered for the edge formation. In this study, the dynamical behavior of such
      networks is examined by considering the example of T4 lysozyme. The equilibrium
      dynamics and the process of unfolding are followed by simulating the protein at
      300 K and at higher temperatures (400 K and 500 K), respectively. The snapshots
      of the protein structure from the simulations are represented as protein
      structure networks in which the strength of the noncovalent interactions is
      considered an important criterion in the construction of edges. The profiles of
      the network parameters, such as the degree distribution and the size of the
      largest cluster (giant component), were examined as a function of interaction
      strength at different temperatures. Similar profiles are seen at all the
      temperatures. However, the critical strength of interaction (Icritical) and the
      size of the largest cluster at all interaction strengths shift to lower values at
      500 K. Further, the folding/unfolding transition is correlated with contacts
      evaluated at Icritical and with the composition of the top large clusters
      obtained at interaction strengths greater than Icritical. Finally, the results
      are compared with experiments, and predictions are made about the residues, which
      are important for stability and folding. To summarize, the network analysis
      presented in this work provides insights into the details of the changes
      occurring in the protein tertiary structure at the level of amino acid side-chain
      interactions, in both the equilibrium and the unfolding simulations. The method
      can also be employed as a valuable tool in the analysis of molecular dynamics
      simulation data, since it captures the details at a global level, which may elude
      conventional pairwise interaction analysis.

PMID- 17208970
TI  - Line FRAP with the confocal laser scanning microscope for diffusion measurements
      in small regions of 3-D samples.
AB  - We present a truly quantitative fluorescence recovery after photobleaching (FRAP)
      model for use with the confocal laser scanning microscope based on the
      photobleaching of a long line segment. The line FRAP method is developed to
      complement the disk FRAP method reported before. Although being more subject to
      the influence of noise, the line FRAP model has the advantage of a smaller bleach
      region, thus allowing for faster and more localized measurements of the diffusion
      coefficient and mobile fraction. The line FRAP model is also very well suited to
      examine directly the influence of the bleaching power on the effective bleaching
      resolution. We present the outline of the mathematical derivation, leading to a
      final analytical expression to calculate the fluorescence recovery. We examine
      the influence of the confocal aperture and the bleaching power on the measured
      diffusion coefficient to find the optimal experimental conditions for the line
      FRAP method. This will be done for R-phycoerythrin and FITC-dextrans of various
      molecular weights. The ability of the line FRAP method to measure correctly
      absolute diffusion coefficients in three-dimensional samples will be evaluated as
      well. Finally we show the application of the method to the simultaneous
      measurement of free green fluorescent protein diffusion in the cytoplasm and
      nucleus of living A549 cells.

PMID- 17208971
TI  - Mechanism of copper mediated triple helix formation at neutral pH in Drosophila
      satellite repeats.
AB  - The highly repeated Drosophila melanogaster AAGAGAG satellite sequence is present
      at each chromosome centromere of the fly. We demonstrate here how, under nearly
      physiological pH conditions, these sequences can form a pyrimidine triple helix
      containing T.A-T and CCu.G-C base triplets, stabilized by Cu2+ metal ions in
      amounts mirroring in vivo concentrations. Ultraviolet experiments were used to
      monitor the triple helix formation at pH 7.2 in presence of Cu2+ ions. Triplex
      melting is observed at 23 degrees C. Furthermore, a characteristic signature of
      triple helix formation was obtained by Fourier transform infrared spectroscopy.
      The stabilization of the C.G-C base triplets at pH 7.2 is shown to occur via
      interactions of Cu2+ ions on the third strand cytosine N3 atom and on the guanine
      N7 atom of the polypurine target strand forming CCu.G-C triplets. Under the same
      neutral pH conditions in absence of Cu2+ ions, the triple helix fails to form.
      Possible biological implications are discussed.

PMID- 17208972
TI  - Photoinduced transformations in bacteriorhodopsin membrane monitored with optical
      microcavities.
AB  - Photoinduced molecular transformations in a self-assembled bacteriorhodopsin (bR)
      monolayer are monitored by observing shifts in the near-infrared resonant
      wavelengths of linearly polarized modes circulating in a microsphere cavity. We
      quantify the molecular polarizability change upon all-trans to 13-cis
      isomerization and deprotonation of the chromophore retinal ( approximately -57
      A(3)) and determine its orientation relative to the bR membrane ( approximately
      61 degrees ). Our observations establish optical microcavities as a sensitive off
      resonant spectroscopic tool for probing conformations and orientations of
      molecular self-assemblies and for measuring changes of molecular polarizability
      at optical frequencies. We provide a general estimate of the sensitivity of the
      technique and discuss possible applications.

PMID- 17208973
TI  - Simulation of the coupling between nucleotide binding and transmembrane domains
      in the ATP binding cassette transporter BtuCD.
AB  - The nucleotide-induced structural rearrangements in ATP binding cassette (ABC)
      transporters, leading to substrate translocation, are largely unknown. We have
      modeled nucleotide binding and release in the vitamin B(12) importer BtuCD using
      perturbed elastic network calculations and biased molecular dynamics simulations.
      Both models predict that nucleotide release decreases the tilt between the two
      transmembrane domains and opens the cytoplasmic gate. Nucleotide binding has the
      opposite effect. The observed coupling may be relevant for all ABC transporters
      because of the conservation of nucleotide binding domains and the shared role of
      ATP in ABC transporters. The rearrangements in the cytoplasmic gate region do not
      provide enough space for B(12) to diffuse from the transporter pore into the
      cytoplasm, which could suggest that peristaltic forces are needed to exclude
      B(12) from the transporter pore.

PMID- 17208974
TI  - A virtual hair cell, II: evaluation of mechanoelectric transduction parameters.
AB  - The virtual hair cell we have proposed utilizes a set of parameters related to
      its mechanoelectric transduction. In this work, we observed the effect of such
      channel gating parameters as the gating threshold, critical tension, resting
      tension, and Ca(2+) concentration. The gating threshold is the difference between
      the resting and channel opening tension exerted by the tip link assembly on the
      channel. The critical tension is the tension in the tip link assembly over which
      the channel cannot close despite Ca(2+) binding. Our results show that 1), the
      gating threshold dominated the initial sensitivity of the hair cell; 2), the
      critical tension minimally affects the peak response, (I), but considerably
      affects the time course of response, I(t), and the force-displacement, F-X,
      relationship; and 3), higher intracellular [Ca(2+)] resulted in a smaller fast
      adaptation time constant. Based on the simulation results we suggest a role of
      the resting tension: to help overcome the viscous drag of the hair bundle during
      the oscillatory movement of the bundle. Also we observed the three-dimensional
      bundle effect on the hair cell response by varying the number of cilia forced.
      These varying forcing conditions affected the hair cell response.

PMID- 17208975
TI  - A virtual hair cell, I: addition of gating spring theory into a 3-D bundle
      mechanical model.
AB  - We have developed a virtual hair cell that simulates hair cell mechanoelectrical
      transduction in the turtle utricle. This study combines a full three-dimensional
      hair bundle mechanical model with a gating spring theory. Previous mathematical
      models represent the hair bundle with a single degree of freedom system which, we
      have argued, cannot fully explain hair bundle mechanics. In our computer model,
      the tip link tension and fast adaptation modulator kinetics determine the opening
      and closing of each channel independently. We observed the response of individual
      transduction channels with our presented model. The simulated results showed
      three features of hair cells in vitro. First, a transient rebound of the bundle
      tip appeared when fast adaptation dominated the dynamics. Second, the dynamic
      stiffness of the bundle was minimized when the response-displacement (I-X) curve
      was steepest. Third, the hair cell showed "polarity", i.e., activation decreased
      from a peak to zero as the forcing direction rotated from the excitatory to the
      inhibitory direction.

PMID- 17208976
TI  - Ion leakage through transient water pores in protein-free lipid membranes driven
      by transmembrane ionic charge imbalance.
AB  - We have employed atomic-scale molecular dynamics simulations to address ion
      leakage through transient water pores in protein-free phospholipid membranes. Our
      results for phospholipid membranes in aqueous solution with NaCl and KCl salts
      show that the formation of transient water pores and the consequent ion leakage
      can be induced and be driven by a transmembrane ionic charge imbalance, an
      inherent feature in living cells. These processes take place if the gradient is
      large enough to develop a sufficiently significant potential difference across
      the membrane. The transport of cations and anions through the water pores is then
      seen; it discharges the transmembrane potential, considerably reduces the size of
      a water pore, and makes the water pore metastable, leading eventually to its
      sealing. The ion transport is found to be sensitive to the type of ions. It turns
      out that Na(+) and Cl(-) ions leak through a membrane at approximately the same
      ratio despite the fact that Na(+) ions are expected to experience a lower
      potential barrier for the permeation through the pore. This is because of strong
      interactions of sodium ions with the carbonyl region of a phospholipid membrane
      as well as with lipid headgroups forming pore "walls," considerably slowing down
      the permeation of sodium ions. In contrast, we observed a pronounced selectivity
      of a phospholipid membrane to the permeation of potassium ions as compared to
      chloride ions: Potassium ions, being larger than sodium ions, interact only
      weakly with phospholipid headgroups, so that these interactions are not able to
      compensate for a large difference in free-energy barriers for permeation of K(+)
      and Cl(-) ions. These findings are found to be robust to a choice of force-field
      parameters for ions (tested by Gromacs and Charmm force-fields for ions). What is
      more, a potassium ion is found to be able to permeate a membrane along an
      alternate, "water-defect-mediated" pathway without actual formation of a pore.
      The "water-defect-mediated" leakage involves formation of a single water defect
      only and is found to be at least one order of magnitude faster than the pore
      mediated ion leakage.

PMID- 17208977
TI  - Structure-based kinetic models of modular signaling protein function: focus on
      Shp2.
AB  - We present here a computational, rule-based model to study the function of the
      SH2 domain-containing protein tyrosine phosphatase, Shp2, in intracellular signal
      transduction. The two SH2 domains of Shp2 differentially regulate the enzymatic
      activity by a well-characterized mechanism, but they also affect the targeting of
      Shp2 to signaling receptors in cells. Our kinetic model integrates these
      potentially competing effects by considering the intra- and intermolecular
      interactions of the Shp2 SH2 domains and catalytic site as well as the effect of
      Shp2 phosphorylation. Even for the isolated Shp2/receptor system, which may seem
      simple by certain standards, we find that the network of possible binding and
      phosphorylation states is composed of over 1000 members. To our knowledge, this
      is the first kinetic model to fully consider the modular, multifunctional
      structure of a signaling protein, and the computational approach should be
      generally applicable to other complex intermolecular interactions.

PMID- 17208978
TI  - Heterologous expression of Pharaonis halorhodopsin in Xenopus laevis oocytes and
      electrophysiological characterization of its light-driven Cl- pump activity.
AB  - Natronomonas pharaonis halorhodopsin (pHR) is an archaeal rhodopsin functioning
      as an inward-directed, light-driven Cl- pump. To characterize the
      electrophysiological features of the Cl- pump activity of pHR, we expressed pHR
      in Xenopus laevis oocytes and analyzed its photoinduced Cl- pump activity using
      the two-electrode voltage-clamp technique. Photoinduced outward currents were
      observed only in the presence of Cl-, Br-, I-, NO3-, and SCN-, but not in control
      oocytes, indicating that photoinduced anion currents were mediated by pHR. The
      relationship between photoinduced Cl- current via pHR and the light intensity was
      linear, demonstrating that transport of Cl- is driven by a single-photon reaction
      and that the steady-state current is proportional to the excited pHR molecule.
      The current-voltage relationship for pHR-mediated photoinduced currents was also
      linear between -150 mV and +50 mV. The slope of the line describing the current
      voltage relationship increased as the number of the excited pHR molecules was
      increased by the light intensity. The reversal potential (VR) for Cl- as the
      substrate for the anion pump activity of pHR was about -400 mV. The value for VR
      was independent of light intensity, meaning that the VR reflects the intrinsic
      value of the excited pHR molecule. The value of VR changed significantly for the
      R123K mutant of pHR. We also show that the Cl- pump activity of pHR can generate
      a substantial negative membrane potential, indicating that pHR is a very potent
      Cl- pump. We have also analyzed the kinetics of voltage-dependent Cl- pump
      activity as well as that of the photocycle. Based on these data, a kinetic model
      for voltage-dependent Cl- transport via pHR is presented.

PMID- 17208979
TI  - Kinetics of internal-loop formation in polypeptide chains: a simulation study.
AB  - The speed of simple diffusional motions, such as the formation of loops in the
      polypeptide chain, places one physical limit on the speed of protein folding.
      Many experimental studies have explored the kinetics of formation of end-to-end
      loops in polypeptide chains; however, protein folding more often requires the
      formation of contacts between interior points on the chain. One expects that, for
      loops of fixed contour length, interior loops will form more slowly than end-to
      end loops, owing to the additional excluded volume associated with the "tails".
      We estimate the magnitude of this effect by generating ensembles of randomly
      coiled, freely jointed chains, and then using the theory of Szabo, Schulten, and
      Schulten to calculate the corresponding contact formation rates for these
      ensembles. Adding just a few residues, to convert an end-to-end loop to an
      internal loop, sharply decreases the contact rate. Surprisingly, the relative
      change in rate increases for a longer loop; sufficiently long tails, however,
      actually reverse the effect and accelerate loop formation slightly. Our results
      show that excluded volume effects in real, full-length polypeptides may cause the
      rates of loop formation during folding to depart significantly from the values
      derived from recent loop-formation experiments on short peptides.

PMID- 17208980
TI  - Poisson-Boltzmann calculations of nonspecific salt effects on protein-protein
      binding free energies.
AB  - The salt dependence of the binding free energy of five protein-protein hetero
      dimers and two homo-dimers/tetramers was calculated from numerical solutions to
      the Poisson-Boltzmann equation. Overall, the agreement with experimental values
      is very good. In all cases except one involving the highly charged lactoglobulin
      homo-dimer, increasing the salt concentration is found both experimentally and
      theoretically to decrease the binding affinity. To clarify the source of salt
      effects, the salt-dependent free energy of binding is partitioned into screening
      terms and to self-energy terms that involve the interaction of the charge
      distribution of a monomer with its own ion atmosphere. In six of the seven
      complexes studied, screening makes the largest contribution but self-energy
      effects can also be significant. The calculated salt effects are found to be
      insensitive to force-field parameters and to the internal dielectric constant
      assigned to the monomers. Nonlinearities due to high charge densities, which are
      extremely important in the binding of proteins to negatively charged membrane
      surfaces and to nucleic acids, make much smaller contributions to the protein
      protein complexes studied here, with the exception of highly charged
      lactoglobulin dimers. Our results indicate that the Poisson-Boltzmann equation
      captures much of the physical basis of the nonspecific salt dependence of protein
      protein complexation.

PMID- 17208981
TI  - Automatic detection of single fluorophores in live cells.
AB  - Recent developments in light microscopy enable individual fluorophores to be
      observed in aqueous conditions. Biological molecules, labeled with a single
      fluorophore, can be localized as isolated spots of light when viewed by optical
      microscopy. Total internal reflection fluorescence microscopy greatly reduces
      background fluorescence and allows single fluorophores to be observed inside
      living cells. This advance in live-cell imaging means that the spatial and
      temporal dynamics of individual molecules can be measured directly. Because of
      the stochastic nature of single molecule behavior a statistically meaningful
      number of individual molecules must be detected and their separate trajectories
      in space and time stored and analyzed. Here, we describe digital image processing
      methods that we have devised for automatic detection and tracking of hundreds of
      molecules, observed simultaneously, in vitro and within living cells. Using this
      technique we have measured the diffusive behavior of pleckstrin homology domains
      bound to phosphoinositide phospholipids at the plasma membrane of live cultured
      mammalian cells. We found that mobility of these membrane-bound protein domains
      is dominated by mobility of the lipid molecule to which they are attached and is
      highly temperature dependent. Movement of PH domains isolated from the tail
      region of myosin-10 is consistent with a simple random walk, whereas, diffusion
      of intact PLC-delta1 shows behavior inconsistent with a simple random walk.
      Movement is rapid over short timescales but much slower at longer timescales.
      This anomalous behavior can be explained by movement being restricted to membrane
      regions of 0.7 microm diameter.

PMID- 17208982
TI  - Mesoscale simulation of blood flow in small vessels.
AB  - Computational modeling of blood flow in microvessels with internal diameter 20
      500 microm is a major challenge. It is because blood in such vessels behaves as a
      multiphase suspension of deformable particles. A continuum model of blood is not
      adequate if the motion of individual red blood cells in the suspension is of
      interest. At the same time, multiple cells, often a few thousands in number, must
      also be considered to account for cell-cell hydrodynamic interaction. Moreover,
      the red blood cells (RBCs) are highly deformable. Deformation of the cells must
      also be considered in the model, as it is a major determinant of many
      physiologically significant phenomena, such as formation of a cell-free layer,
      and the Fahraeus-Lindqvist effect. In this article, we present two-dimensional
      computational simulation of blood flow in vessels of size 20-300 microm at
      discharge hematocrit of 10-60%, taking into consideration the particulate nature
      of blood and cell deformation. The numerical model is based on the immersed
      boundary method, and the red blood cells are modeled as liquid capsules. A large
      RBC population comprising of as many as 2500 cells are simulated. Migration of
      the cells normal to the wall of the vessel and the formation of the cell-free
      layer are studied. Results on the trajectory and velocity traces of the RBCs, and
      their fluctuations are presented. Also presented are the results on the plug-flow
      velocity profile of blood, the apparent viscosity, and the Fahraeus-Lindqvist
      effect. The numerical results also allow us to investigate the variation of
      apparent blood viscosity along the cross-section of a vessel. The computational
      results are compared with the experimental results. To the best of our knowledge,
      this article presents the first simulation to simultaneously consider a large
      ensemble of red blood cells and the cell deformation.

PMID- 17208983
TI  - Attachment conditions control actin filament buckling and the production of
      forces.
AB  - Actin polymerization is the driving force for a large number of cellular
      processes. Formation of lamellipodia and filopodia at the leading edge of motile
      cells requires actin polymerization induced mechanical deformation of the plasma
      membrane. To generate different types of membrane protrusions, the mechanical
      properties of actin filaments can be constrained by interacting proteins. A
      striking example of such constraint is the buckling of actin filaments generated
      in vitro by the cooperative effect of a processive actin nucleating factor
      (formin) and a molecular motor (myosin II). We developed a physical model based
      on equations for an elastic rod that accounts for actin filament buckling. Both
      ends of the rod were maintained in a fixed position in space and we considered
      three sets of boundary conditions. The model qualitatively and quantitatively
      reproduces the shape distribution of actin filaments. We found that actin
      polymerization counterpoises a force in the range 0.4-1.6 pN for moderate end-to
      end distance (approximately 1 microm) and could be as large as 10 pN for shorter
      distances. If the actin rod attachment includes a spring, we discovered that the
      stiffness must be in the range 0.1-1.2 pN/nm to account for the observed
      buckling.

PMID- 17208984
TI  - Electrostatic interactions modulate the conformation of collagen I.
AB  - The pH- and electrolyte-dependent charging of collagen I fibrils was analyzed by
      streaming potential/streaming current experiments using the Microslit
      Electrokinetic Setup. Differential scanning calorimetry and circular dichroism
      spectroscopy were applied in similar electrolyte solutions to characterize the
      influence of electrostatic interactions on the conformational stability of the
      protein. The acid base behavior of collagen I was found to be strongly influenced
      by the ionic strength in KCl as well as in CaCl(2) solutions. An increase of the
      ionic strength with KCl from 10(-4) M to 10(-2) M shifts the isoelectric point
      (IEP) of the protein from pH 7.5 to 5.3. However, a similar increase of the ionic
      strength in CaCl(2) solutions shifts the IEP from 7.5 to above pH 9. Enhanced
      thermal stability with increasing ionic strength was observed by differential
      scanning calorimetry in both electrolyte systems. In line with this, circular
      dichroism spectroscopy results show an increase of the helicity with increasing
      ionic strength. Better screening of charged residues and the formation of salt
      bridges are assumed to cause the stabilization of collagen I with increasing
      ionic strength in both electrolyte systems. Preferential adsorption of hydroxide
      ions onto intrinsically uncharged sites in KCl solutions and calcium binding to
      negatively charged carboxylic acid moieties in CaCl(2) solutions are concluded to
      shift the IEP and influence the conformational stability of the protein.

PMID- 17208985
TI  - Thermodynamically feasible kinetic models of reaction networks.
AB  - The dynamics of biological reaction networks are strongly constrained by
      thermodynamics. An holistic understanding of their behavior and regulation
      requires mathematical models that observe these constraints. However, kinetic
      models may easily violate the constraints imposed by the principle of detailed
      balance, if no special care is taken. Detailed balance demands that in
      thermodynamic equilibrium all fluxes vanish. We introduce a thermodynamic-kinetic
      modeling (TKM) formalism that adapts the concepts of potentials and forces from
      irreversible thermodynamics to kinetic modeling. In the proposed formalism, the
      thermokinetic potential of a compound is proportional to its concentration. The
      proportionality factor is a compound-specific parameter called capacity. The
      thermokinetic force of a reaction is a function of the potentials. Every reaction
      has a resistance that is the ratio of thermokinetic force and reaction rate. For
      mass-action type kinetics, the resistances are constant. Since it relies on the
      thermodynamic concept of potentials and forces, the TKM formalism structurally
      observes detailed balance for all values of capacities and resistances. Thus, it
      provides an easy way to formulate physically feasible, kinetic models of
      biological reaction networks. The TKM formalism is useful for modeling large
      biological networks that are subject to many detailed balance relations.

PMID- 17208986
TI  - Transient diffusion of albumin in aortic walls: effects of binding to medial
      elastin layers.
AB  - The goal of this study was to measure diffusive transport of albumin through
      artery walls experimentally and to analyze the results theoretically, taking into
      account the binding of albumin to elastic lamellae. Segments of rabbit aorta were
      placed in solutions of fluorescently labeled albumin for periods of 30, 60, 90,
      and 120 min, and the distributions of fluorescence intensity through the arterial
      media were observed. On average, intensity increased almost linearly with time.
      Bands of high intensity were observed corresponding to elastin layers within the
      media. The temporal and spatial variations of intensity were compared with
      predictions of theoretical models, including effects of albumin binding and
      hindered diffusion resulting from the complex wall structure. Based on these
      analyses, it was concluded that the spatial distribution of free albumin within
      the media equilibrated relatively rapidly, and that the observed linear increase
      in intensity reflected gradual accumulation of albumin bound to medial elastin
      layers. The results imply that previous theoretical analyses, in which binding
      was neglected, substantially underestimated albumin diffusivity in the aortic
      wall. With respect to stent-associated delivery of inhibitors of vascular cell
      proliferation, the results suggest that albumin might serve as an "affinity
      vehicle" for drug delivery to the aorta, by attaching the drug to an abundant
      component of the artery wall.

PMID- 17208987
TI  - Expression of an angiotensin-(1-7)-producing fusion protein in rats induced
      marked changes in regional vascular resistance.
AB  - We have described a transgenic rat line that expresses an angiotensin-(1-7)
      producing fusion protein, the TGR(A1-7)3292. In these rats, testis acts as an
      angiotensin-(1-7) biological pump, increasing its plasma concentration 2.5-fold.
      In this study, we performed hemodynamic measurements in TGR(A1-7)3292 and age
      matched Hannover Sprague-Dawley (SD) control rats, using fluorescent
      microspheres. Urethane-anesthetized transgenic rats had similar levels of
      baseline blood pressure (99 +/- 3 mmHg) as did SD rats (101 +/- 3 mmHg). However,
      pronounced differences were observed in other hemodynamic measurements. TGR(A1
      7)3292 rats presented a significant increase in stroke volume (0.29 +/- 0.01 vs.
      0.25 +/- 0.01 ml in SD), increased cardiac index (24.6 +/- 0.91 vs. 21.9 +/- 0.65
      ml.min(-1).kg) and decreased total peripheral resistance (3.9 +/- 0.13 vs. 4.5 +/
      0.13 mmHg.ml(-1).min.100 g). The increase in stroke volume in transgenic rats
      may be partially explained by the small decrease in heart rate (326 +/- 7.0 vs.
      359 +/- 6.0 beats/min in SD). Strikingly, TGR(A1-7)3292 rats presented a
      substantial decrease in the vascular resistance in lung, spleen, kidney,
      adrenals, brain, testis and brown fat tissue with no significant differences in
      the left ventricle, mesentery, skin, gastrocnemius muscle and white fat tissue.
      These results corroborate and extend previous results observed after acute
      angiotensin-(1-7) infusion, showing that chronic increase in circulating
      angiotensin-(1-7) produces sustained and important changes in regional and
      systemic hemodynamics. Moreover, our data suggest a physiological role for
      angiotensin-(1-7) in the tonic control of regional blood flow.

PMID- 17208988
TI  - Inhibition of Fas-associated apoptosis in granulation tissue cells accompanies
      attenuation of postinfarction left ventricular remodeling by olmesartan.
AB  - Blockade of angiotensin II type 1 receptor (AT1) signaling attenuates heart
      failure following myocardial infarction (MI), perhaps through reduction of
      fibrosis in the noninfarcted myocardium. However, its specific effect on the
      infarct tissue itself has not been fully clarified, which we examined in the
      present study. After MI induction in mice, treatment with the AT1 blocker
      olmesartan, beginning on the 3rd day post-MI, significantly improved survival
      (94%) 4 wk post-MI, compared with saline (53%) and hydralazine (73%). Olmesartan
      treated mice also showed significant attenuation of left ventricular dilatation
      and dysfunction, as well as significantly greater infarct wall thickness,
      although the absolute size of the infarct scar was unchanged. In addition,
      significantly greater numbers of nonmyocytes (mainly vascular cells and
      myofibroblasts) were present within the infarct scar in olmesartan-treated
      hearts. Ten days post-MI, apoptosis among granulation tissue cells was
      significantly suppressed in the olmesartan-treated hearts, where expression of
      Fas, Bax, procaspase-3, and Daxx and activation of caspase-3, c-Jun NH(2)
      terminal kinase, and c-Jun were all significantly attenuated. By contrast,
      expression of Fas ligand, Bcl-2, and Fas-associated death domain and activation
      of caspase-8 were unaffected, suggesting olmesartan exerts a negative regulatory
      effect on the alternate pathway downstream of Fas receptor. In vitro, olmesartan
      dose-dependently inhibited Fas-mediated apoptosis in granulation tissue-derived
      myofibroblasts. The present study proposes this antiapoptotic effect as another
      important mechanism for an AT1 blocker in improving post-MI ventricular
      remodeling, as well as its antifibrotic effect, and also suggests a significant
      link between renin-angiotensin and Fas/Fas ligand systems in postinfarction
      hearts.

PMID- 17208989
TI  - Impaired myocardial perfusion reserve in experimental hypercholesterolemia is
      independent of myocardial neovascularization.
AB  - Our objective was to investigate the functional role of hypercholesterolemia
      associated myocardial neovascularization in early atherosclerosis using the
      antiangiogenic thalidomide. Experimental atherosclerosis is characterized by
      myocardial neovascularization, associated with a decrease in myocardial perfusion
      response to challenge, coronary endothelial dysfunction, and high oxidative
      stress. However, the functional significance of these neovessels is not known.
      Three groups of pigs (n = 6 each) were studied after 12 wk of normal or
      hypercholesterolemic diet without (HC) or with thalidomide (HC + Thal).
      Myocardial perfusion and permeability were assessed at baseline and in response
      to cardiac challenge, using electron beam computed tomography, and coronary
      endothelial function was assessed using organ chambers. Myocardial samples were
      scanned ex vivo with a three-dimensional microscopic computed tomography scanner,
      and the spatial density of the myocardial microvessels was quantified. Growth
      factors and oxidative stress were measured in the myocardial tissue. As a results
      of these procedures, myocardial perfusion response to adenosine and dobutamine
      was blunted in both HC and HC + Thal pigs compared with normal pigs (P < 0.05, HC
      and HC + Thal vs. normal) as was the coronary endothelial function. Myocardial
      permeability response to adenosine was increased in both HC and HC + Thal pigs
      compared with normal pigs (P < 0.05, HC and HC + Thal vs. normal, and HC + Thal
      vs. HC). The microvascular density was increased in HC pigs compared with normal
      pigs but normalized in HC + Thal pigs (P < 0.001 HC vs. normal and HC + Thal). HC
      + Thal pigs showed decreased expression of Flk-1 and basic FGF but increased
      expression of VEGF compared with normal and HC pigs. Oxidative stress was
      increased in both HC and HC + Thal pigs compared with normal pigs. In conclusion,
      chronic administration of thalidomide attenuates myocardial neovascularization in
      experimental HC pigs without affecting myocardial perfusion response to
      stimulation. This suggests that the myocardial neovascularization may not
      contribute to the attenuated myocardial perfusion response in
      hypercholesterolemia.

PMID- 17208990
TI  - Norepinephrine and endothelin activate diacylglycerol kinases in caveolae/rafts
      of rat mesenteric arteries: agonist-specific role of PI3-kinase.
AB  - The phosphatidylinositol (PI) signaling pathway mediates norepinephrine (NE)- and
      endothelin-1 (ET-1)-stimulated vascular smooth muscle contraction through an
      inositol-trisphosphate-induced rise in intracellular calcium and diacylglycerol
      (DG) activation of protein kinase C (PKC). Subsequent activation of DG kinases
      (DGKs) metabolizes DG to phosphatidic acid (PA), potentially regulating PKC
      activity. Because precise regulation and spatial restriction of the PI pathway is
      necessary for specificity, we have investigated whether this occurs within
      caveolae/rafts, specialized plasma membrane microdomains implicated in vascular
      smooth muscle contraction. We show that components of the PI signaling cascade
      phosphatidylinositol 4,5-bisphosphate (PIP(2)), PA, and DGK-theta are present in
      caveolae/rafts prepared from rat mesenteric small arteries. Stimulation with NE
      or ET-1 induced [(33)P]PIP(2) hydrolysis solely within caveolae/rafts. NE
      stimulated an increase in DGK activity in caveolae/rafts alone, whereas ET-1
      activated DGK in caveolae/rafts and noncaveolae/rafts; however, [(33)P]PA
      increased in all fractions with both agonists. Previously, we reported that NE
      activated DGK-theta in a phosphatidylinositol 3-kinase (PI3-kinase)-dependent
      manner; here, we describe PI3-kinase-dependent DGK activation and [(33)P]PA
      production in caveolae/rafts in response to NE but not ET-1. Additionally, PKB, a
      potential activator of DGK-theta, translocated to caveolae/rafts in response to
      NE but not ET-1, and PI3-kinase inhibition prevented this. Furthermore, PI3
      kinase inhibition reduced the sensitivity of contraction to NE but not ET-1. Our
      study shows that caveolae/rafts are major sites of vasoconstrictor hormone
      activation of the PI pathway in intact small arteries and suggest a link between
      lipid signaling events within caveolae/rafts and contraction.

PMID- 17208991
TI  - Chronic preconditioning: a novel approach for cardiac protection.
AB  - Ischemic preconditioning is the most powerful protective mechanism known against
      lethal ischemia. Unfortunately, the protection lasts for only a few hours. Here
      we tested the hypothesis that the heart can be kept in a preconditioned state for
      constant protection against ischemia. In this study we chose BMS-191095 (BMS), a
      highly selective opener of mitochondrial ATP-sensitive K(+) (mitoK(ATP))
      channels. BMS (1 mg/kg ip) was administered to rats every 24 h until 96 h. In
      other groups, BMS plus wortmannin (WTN, 15 microg/kg ip), an inhibitor of the
      phosphatidylinositol 3-kinase (PI3-K), or BMS plus 5-hydroxydecanoic acid (5-HD,
      5 mg/kg ip), an inhibitor of mitoK(ATP), or BMS plus N(omega)-nitro-L-arginine
      methyl ester (L-NAME) (30 microg/kg ip), an inhibitor of nitric oxide (NO)
      synthase, were administered to rats. Rats were then subjected to 30-min left
      anterior descending coronary artery occlusion and 120-min reperfusion. Cardiac
      function, infarct size, pathological changes, and apoptosis were assessed at the
      end of treatments. Saline-treated hearts displayed marked contractile dysfunction
      and underwent pathological changes. BMS-treated rats showed significant
      improvement in cardiac function, and infarct size was significantly reduced in
      BMS-treated hearts. However, protection by BMS was abolished by 5-HD, WTN, or L
      NAME. These data demonstrate that hearts can be chronically preconditioned and
      retain their ability to remain resistant against lethal ischemia and that this
      protection is mediated by activation of mitoK(ATP) via NO and PI3-K/Akt signaling
      pathways.

PMID- 17208992
TI  - Blind identification of the aortic pressure waveform from multiple peripheral
      artery pressure waveforms.
AB  - We have developed a new technique to estimate the clinically relevant aortic
      pressure waveform from multiple, less invasively measured peripheral artery
      pressure waveforms. The technique is based on multichannel blind system
      identification in which two or more measured outputs (peripheral artery pressure
      waveforms) of a single-input, multi-output system (arterial tree) are
      mathematically analyzed so as to reconstruct the common unobserved input (aortic
      pressure waveform) to within an arbitrary scale factor. The technique then
      invokes Poiseuille's law to calibrate the reconstructed waveform to absolute
      pressure. Consequently, in contrast to previous related efforts, the technique
      does not utilize a generalized transfer function or any training data and is
      therefore entirely patient and time specific. To demonstrate proof of concept, we
      have evaluated the technique with respect to four swine in which peripheral
      artery pressure waveforms from the femoral and radial arteries and a reference
      aortic pressure waveform from the descending thoracic aorta were simultaneously
      measured during diverse hemodynamic interventions. We report that the technique
      reliably estimated the entire aortic pressure waveform with an overall root mean
      squared error (RMSE) of 4.6 mmHg. For comparison, the average overall RMSE
      between the peripheral artery pressure and reference aortic pressure waveforms
      was 8.6 mmHg. Thus the technique reduced the RMSE by 47%. As a result, the
      technique also provided similar improvements in the estimation of systolic
      pressure, pulse pressure, and the ejection interval. With further successful
      testing, the technique may ultimately be employed for more precise monitoring and
      titration of therapy in, for example, critically ill and hypertension patients.

PMID- 17208993
TI  - Release of TNF-alpha during stent implantation into saphenous vein aortocoronary
      bypass grafts and its relation to plaque extrusion and restenosis.
AB  - The reduction in plaque volume during stent implantation is associated with the
      release of particulate debris and plaque-derived soluble substances. We studied
      the potential release of the proinflammatory cytokine TNF-alpha into the coronary
      circulation and whether such release is related to the reduction in plaque volume
      and, possibly, a predictor for restenosis. In 18 male patients (n = 24 stents)
      with severe stenosis in a saphenous vein aortocoronary bypass graft (SVG), we
      used a distal balloon occlusion-aspiration device during stent implantation. The
      aspirate TNF-alpha levels were determined before and after stent implantation and
      related to the angiographic and intravascular ultrasound-assessed severity of
      stenosis and restenosis. We found that TNF-alpha is, indeed, released into the
      aspirate of stented SVG (9 +/- 1 and 28 +/- 3 pg/ml before and after stent
      implantation, respectively, P < 0.0001) and that such release is related to the
      reduction in plaque volume (r = 0.88, P < 0.0001) and associated with restenosis
      after 5 mo (r = 0.71, P = 0.001). The periprocedural release of plaque-derived
      TNF-alpha possibly represents the amount and activity of the atherosclerotic
      process and might be a predictor for restenosis.

PMID- 17208994
TI  - Glucosamine cardioprotection in perfused rat hearts associated with increased O
      linked N-acetylglucosamine protein modification and altered p38 activation.
AB  - We have shown that, in the perfused heart, glucosamine improved functional
      recovery following ischemia and that this appeared to be mediated via an increase
      in O-linked N-acetylglucosamine (O-GlcNAc) levels on nucleocytoplasmic proteins.
      Several kinase pathways, specifically Akt and the mitogen-activated protein
      kinases (MAPKs) p38 and ERK1/2, which have been implicated in ischemic
      cardioprotection, have also been reported to be modified in response to increased
      O-GlcNAc levels. Therefore, the goals of this study were to determine the effect
      of ischemia on O-GlcNAc levels and to evaluate whether the cardioprotection
      resulting from glucosamine treatment could be attributed to changes in ERK1/2,
      Akt, and p38 phosphorylation. Isolated rat hearts were perfused with or without 5
      mM glucosamine and were subjected to 5, 10, or 30 min of low-flow ischemia or 30
      min of low-flow ischemia and 60 min of reperfusion. Glucosamine treatment
      attenuated ischemic contracture and improved functional recovery at the end of
      reperfusion. Glucosamine treatment increased flux through the hexosamine
      biosynthesis pathway and increased O-GlcNAc levels but had no effect on ATP
      levels. Glucosamine did not alter the response of either ERK1/2 or Akt to
      ischemia-reperfusion; however, it significantly attenuated the ischemia-induced
      increase in p38 phosphorylation and paradoxically increased p38 phosphorylation
      at the end of reperfusion. These data support the notion that O-GlcNAc may play
      an important role as an internal stress response and that glucosamine-induced
      cardioprotection may be mediated via the p38 MAPK pathway.

PMID- 17208995
TI  - Influence of PKC-alpha overexpression on HSP70 and cardioprotection.
AB  - Recent research has indicated that the protein kinase C (PKC) isoforms and the
      heat shock proteins (HSPs) are involved in cardioprotection. We have investigated
      the possible interaction between these two protein families. We have found that
      adenoviral-mediated expression of PKC-alpha in neonatal rat ventricular myocytes
      (NRVM) not only increases the expression of HSP70 but also protects against
      simulated ischemia-reperfusion. In addition, Western blots of PKC-alpha-infected
      NRVM indicated that other HSPs are not induced in the same manner as HSP70. In an
      effort to determine the mechanism of induction of HSP70 by PKC-alpha, we tested a
      chimeric construct that linked the luciferase reporter gene to the 5'-promoter
      region of HSP70 in myogenic H9c2 cells. When PKC-alpha was expressed, the 5'
      promoter region of the HSP70 responded robustly, indicating that PKC-alpha
      induction of HSP70 expression is through transcription activation.
      Electrophoretic mobility shift assay determined that overexpression of PKC-alpha,
      PKC-delta, or PKC-epsilon did not induce activation of heat shock factor-1 (HSF
      1). Therefore, induction of HSP70 by PKC-alpha is independent of heat shock
      factor-1 activation. We also measured cellular injury by assessing creatine
      kinase (CK) release from NRVM after simulated ischemia to determine
      cardioprotection. NRVM infected with the wild-type adenoviral construct AdwtPKC
      alpha released 54% less CK than control NRVM. Experiments using small interfering
      RNA against HSP70 indicate that loss of PKC-alpha-induced HSP70 expression
      results in increased CK release or a loss of protection. Our results show that
      there is a close interaction between PKC-alpha and HSP70, independent of heat
      shock factor-1 activation, and that the protection conferred by PKC-alpha
      overexpression is mediated by the transcriptionally induced expression of HSP70.

PMID- 17208996
TI  - Age alters cerebrovascular inflammation and effects of estrogen.
AB  - In young adult females, estrogen treatment suppresses the cerebrovascular
      inflammatory response; this is mediated in part via NF-kappaB, a key regulator of
      inflammatory genes. To examine whether age modifies effects of estrogen on
      vascular inflammation in the brain, female rats, 3 and 12 mo of age, were
      ovariectomized; half were treated with estrogen for 4 wk. Cerebral blood vessels
      were isolated from the animals at 4 and 13 mo of age. Inflammation was induced by
      LPS, either injected in vivo or incubated with isolated vessels ex vivo. Basal
      levels of cytoplasmic NF-kappaB were significantly higher in cerebral vessels of
      young rats, but the ratio of nuclear to cytoplasmic levels was greater in middle
      aged animals. LPS exposure increased nuclear NF-kappaB DNA binding activity,
      protein levels of inducible nitric oxide synthase and cyclooxygenase-2, and
      production of nitric oxide and PGE(2) in cerebral vessels. All effects of LPS
      were markedly greater in vessels from the older animals. Estrogen significantly
      inhibited the LPS-induced increase in NF-kappaB DNA binding activity in cerebral
      vessels from animals at both ages. In 4-mo-old rats, estrogen also significantly
      suppressed LPS induction of inducible nitric oxide synthase and cyclooxygenase-2
      proteins, as well as production of nitric oxide and PGE(2). In contrast, in 13-mo
      old females, estrogen did not significantly affect these indexes of
      cerebrovascular inflammation. Thus the protective, anti-inflammatory effect of
      estrogen on cerebral blood vessels that is observed in young adults may be
      attenuated in aged animals, which exhibit a greater overall cerebrovascular
      response to inflammatory stimuli.

PMID- 17208997
TI  - Prolonged transient acidosis during early reperfusion contributes to the
      cardioprotective effects of postconditioning.
AB  - We have previously reported that the prolonged transient acidosis during early
      reperfusion mediates the cardioprotective effects in canine hearts. Recently,
      postconditioning has been shown to be one of the novel strategies to mediate
      cardioprotection. We tested the contribution of the prolonged transient acidosis
      to the cardioprotection of postconditioning. Open-chest anesthetized dogs
      subjected to 90-min occlusion of the left anterior descending coronary artery and
      6-h reperfusion were divided into four groups: 1) control group; no intervention
      after reperfusion (n = 6); 2) postconditioning (Postcon) group; four cycles of 1
      min reperfusion and 1-min reocclusion (n = 7); 3) Postcon + sodium bicarbonate
      (NaHCO(3)) group; four cycles of 1-min reperfusion and 1-min reocclusion with the
      administration of NaHCO(3) (n = 8); and 4) NaHCO(3) group; administration of
      NaHCO(3) without postconditioning (n = 6). Infarct size, the area at risk (AAR),
      collateral blood flow during ischemia, and pH in coronary venous blood were
      measured. The phosphorylation of Akt and extracellular signal-regulated kinase
      (ERK) in ischemic myocardium was assessed by Western blot analysis. Systemic
      hemodynamic parameters, AAR, and collateral blood flow were not different among
      the four groups. Postconditioning induced prolonged transient acidosis during the
      early reperfusion phase. Administration of NaHCO(3) completely abolished the
      infarct size-limiting effects of postconditioning. Furthermore, the
      phosphorylation of Akt and ERK in ischemic myocardium induced by postconditioning
      was also blunted by the cotreatment of NaHCO(3). In conclusion, postconditioning
      mediates its cardioprotective effects possibly via prolonged transient acidosis
      during the early reperfusion phase with the activation of Akt and ERK.

PMID- 17208998
TI  - A hybrid one-dimensional/Womersley model of pulsatile blood flow in the entire
      coronary arterial tree.
AB  - Using a frequency-domain Womersley-type model, we previously simulated pulsatile
      blood flow throughout the coronary arterial tree. Although this model represents
      a good approximation for the smaller vessels, it does not take into account the
      nonlinear convective energy losses in larger vessels. Here, using Womersley's
      theory, we present a hybrid model that considers the nonlinear effects for the
      larger epicardial arteries while simulating the distal vessels (down to the 1st
      capillary segments) with the use of Womersley's Theory. The main trunk and
      primary branches were discretized and modeled with one-dimensional Navier-Stokes
      equations, while the smaller-diameter vessels were treated as Womersley-type
      vessels. Energy losses associated with vessel bifurcations were incorporated in
      the present analysis. The formulation enables prediction of impedance and
      pressure and pulsatile flow distribution throughout the entire coronary arterial
      tree down to the first capillary segments in the arrested, vasodilated state. We
      found that the nonlinear convective term is negligible and the loss of energy at
      a bifurcation is small in the larger epicardial vessels of an arrested heart.
      Furthermore, we found that the flow waves along the trunk or at the primary
      branches tend to scale (normalized with respect to their mean values) to a single
      curve, except for a small phase angle difference. Finally, the model predictions
      for the inlet pressure and flow waves are in excellent agreement with previously
      published experimental results. This hybrid one-dimensional/Womersley model is an
      efficient approach that captures the essence of the hemodynamics of a complex
      large-scale vascular network. The present model has numerous applications to
      understanding the dynamics of coronary circulation.

PMID- 17208999
TI  - Role of the renin-angiotensin system in the systemic microvascular inflammation
      of alveolar hypoxia.
AB  - Alveolar hypoxia (AH) induces widespread systemic inflammation. Previous studies
      have shown dissociation between microvascular Po(2) and inflammation.
      Furthermore, plasma from AH rats (PAHR) induces mast cell (MC) activation,
      inflammation, and vasoconstriction in normoxic cremasters, while plasma from
      normoxic rats does not produce these responses. These results suggest that
      inflammation of AH is triggered by a blood-carried agent. This study investigated
      the involvement of the renin-angiotensin system (RAS) in the inflammation of AH.
      Both an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin II (ANG
      II) receptor blocker (ANG II RB) inhibited the leukocyte-endothelial adherence
      produced by AH, as well as the inflammation produced by PAHR in normoxic rat
      cremasters. MC stabilization with cromolyn blocked the effects of PAHR but not
      those of topical ANG II on normoxic cremasters, suggesting ANG II generation via
      MC activation by PAHR. This was supported by the observation that ACE inhibition
      and ANG II RB blocked the leukocyte-endothelial adherence produced by the MC
      secretagogue compound 48/80. These results suggest that the intermediary agent
      contained in PAHR activates MC and stimulates the RAS, leading to inflammation,
      and imply an RAS role in AH-induced inflammation.

PMID- 17209000
TI  - Reduced expression of SKCa and IKCa channel proteins in rat small mesenteric
      arteries during angiotensin II-induced hypertension.
AB  - Ca(2+)-activated K(+) channels (K(Ca)), in particular, the small and intermediate
      K(Ca) (SK(Ca) and IK(Ca), respectively) channels, are key players in endothelium
      derived hyperpolarizing factor (EDHF)-mediated relaxation in small arteries.
      Hypertension is characterized by an endothelial dysfunction, possibly via reduced
      EDHF release and/or function. We hypothesize that during angiotensin II (14 days)
      induced hypertension (ANG II-14d), the contribution of SK(Ca) and IK(Ca) channels
      in ACh-induced relaxations is reduced due to decreased expression of SK(Ca) and
      IK(Ca) channel proteins in rat small mesenteric arteries (MAs). Nitric oxide- and
      prostacyclin-independent vasorelaxation to ACh was similar in small MAs of sham
      operated and ANG II-14d rats. Catalase had no inhibitory effects on these
      relaxations. The highly selective SK(Ca) channel blocker UCL-1684 almost
      completely blocked these responses in MAs of sham-operated rats but partially in
      MAs of ANG II-14d rats. These changes were pressure dependent since UCL-1684
      caused a greater inhibition in MAs of 1-day ANG II-treated normotensive rats
      compared with ANG II-14d rats. Expression levels of both mRNA and protein SK3
      were significantly reduced in MAs of ANG II-14d rats. The IK(Ca) channel blocker
      1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) resulted in comparable
      reductions in the relaxation responses to ACh in MAs of sham-operated and ANG II
      14d rats. Relative mRNA expression levels of IK1 were significantly reduced in
      MAs of ANG II-14d rats, whereas protein levels of IK1 were not but tended to be
      lower in MAs of ANG II-14d rats. The findings demonstrate that EDHF-like
      responses are not compromised in a situation of reduced functional activity and
      expression of SK3 channels in small MAs of ANG II-induced hypertensive rats. The
      role of IK1 channels is less clear but might compensate for reduced SK3 activity.

PMID- 17209001
TI  - Overexpression of the Na+/H+ exchanger and ischemia-reperfusion injury in the
      myocardium.
AB  - In the myocardium, the Na(+)/H(+) exchanger isoform-1 (NHE1) activity is
      detrimental during ischemia-reperfusion (I/R) injury, causing increased
      intracellular Na(+) (Na(i)(+)) accumulation that results in subsequent Ca(2+)
      overload. We tested the hypothesis that increased expression of NHE1 would
      accentuate myocardial I/R injury. Transgenic mice were created that increased the
      Na(+)/H(+) exchanger activity specifically in the myocardium. Intact hearts from
      transgenic mice at 10-15 wk of age showed no change in heart performance, resting
      intracellular pH (pH(i)) or phosphocreatine/ATP levels. Transgenic and wild-type
      (WT) hearts were subjected to 20 min of ischemia followed by 40 min of
      reperfusion. Surprisingly, the percent recovery of rate-pressure product (%RPP)
      after I/R improved in NHE1-overexpressing hearts (64 +/- 5% vs. 41 +/- 5% in WT;
      P < 0.05). In addition, NMR spectroscopy revealed that NHE1 overexpressor hearts
      contained higher ATP during early reperfusion (levels P < 0.05), and there was no
      difference in Na(+) accumulation during I/R between transgenic and WT hearts.
      HOE642 (cariporide), an NHE1 inhibitor, equivalently protected both WT and NHE1
      overexpressing hearts. When hearts were perfused with bicarbonate-free HEPES
      buffer to eliminate the contribution of HCO(3)(-) transporters to pH(i)
      regulation, there was no difference in contractile recovery after reperfusion
      between controls and transgenics, but NHE1-overexpressing hearts showed a greater
      decrease in ATP during ischemia. These results indicate that the basal activity
      of NHE1 is not rate limiting in causing damage during I/R, therefore, increasing
      the level of NHE1 does not enhance injury and can have some small protective
      effects.

PMID- 17209002
TI  - Frequency-dependent acceleration of relaxation involves decreased myofilament
      calcium sensitivity.
AB  - The force-frequency relationship is an intrinsic modulator of cardiac
      contractility and relaxation. Force of contraction increases with frequency,
      while simultaneously a frequency-dependent acceleration of relaxation occurs.
      While frequency dependency of calcium handling and sarcoplasmic reticulum calcium
      load have been well described, it remains unknown whether frequency-dependent
      changes in myofilament calcium sensitivity occur. We hypothesized that an
      increase in heart rate that results in acceleration of relaxation is accompanied
      by a proportional decrease in myofilament calcium sensitivity. To test our
      hypothesis, ultrathin right ventricular trabeculae were isolated from New Zealand
      White rabbit hearts and iontophorically loaded with the calcium indicator bis
      fura 2. Twitch and intracellular calcium handling parameters were measured and
      showed a robust increase in twitch force, acceleration of relaxation, and rise in
      both diastolic and systolic intracellular calcium concentration with increased
      frequency. Steady-state force-intracellular calcium concentration relationships
      were measured at frequencies 1, 2, 3, and 4 Hz at 37 degrees C using potassium
      induced contractures. EC(50) significantly and gradually increased with
      frequency, from 475 +/- 64 nM at 1 Hz to 1,004 +/- 142 nM at 4 Hz (P < 0.05) and
      correlated with the corresponding changes in half relaxation time. No significant
      changes in maximal active force development or in the myofilament cooperativity
      coefficient were found. Myofilament protein phosphorylation was assessed using
      Pro-Q Diamond staining on protein gels of trabeculae frozen at either 1 or 4 Hz,
      revealing troponin I and myosin light chain-2 phosphorylation associated with the
      myofilament desensitization. We conclude that myofilament calcium sensitivity is
      substantially and significantly decreased at higher frequencies, playing a
      prominent role in frequency-dependent acceleration of relaxation.

PMID- 17209003
TI  - Transport in rat vessel walls. II. Macromolecular leakage and focal spot size
      growth in rat arteries and veins.
AB  - Transendothelial lipid transport into and spread in the subendothelial intima of
      large arteries, and subsequent lipid accumulation, appear to start plaque
      formation. We experimentally examine transendothelial horseradish peroxidase
      (HRP) transport in vessels that are usually, e.g., pulmonary artery (PA), or
      almost always, e.g., inferior vena cava (IVC), atherosclerosis resistant vs.
      disease prone, e.g., aorta, vessels. In these vessels, HRP traverses the
      endothelium at isolated, focal spots, rather than uniformly, for short
      circulation times. For femoral vein HRP introduction, PA spots have 30-s radii [
      approximately 53.2 microm (SD 10.4); compare aorta: 54.6 microm (SD 8.75)] and
      grow quickly from 30 s to 1 min (40%, P<0.05) and more slowly afterward (P>0.05).
      This trend resembles the aorta, suggesting the PA has a similarly sparse intima.
      With carotid artery (CA) HRP introduction, the 30-s spot (132.86 +/- 37.32
      microm) is far larger than the PAs, grows little ( approximately 28%, P<0.05)
      from 30 to 60 s, and is much flatter than the artery curves. Transverse electron
      microscopic sections after approximately 10 min HRP circulation show thin,
      intense staining immediately beneath both vessels' endothelia with an almost step
      change to diffuse staining beyond. This indicates the existence of a sparse,
      subendothelial intima, even when there is no internal elastic lamina (IVC). This
      motivates a simple model that translates growth rates into lower bounds for the
      flow through focal leaks. The model results and our earlier wall and medial
      hydraulic conductivity data explain these spot growth curves and point to
      differences in transport patterns that might be relevant in understanding the
      immunity of IVC to disease initiation.

PMID- 17209004
TI  - Vascular bed origin dictates flow pattern regulation of endothelial adhesion
      molecule expression.
AB  - Endothelial cell phenotypes markedly differ, depending upon function and vascular
      bed of origin. Differences might account for specific susceptibility to
      pathological conditions. As leukocyte adhesion to activated endothelium is the
      initiating event in a range of diseases, we compared the influence of vascular
      bed-specific flow patterns on adhesion molecule expression in human saphenous
      vein (HSVEC) and coronary artery endothelial cells (HCAEC). In vitro, immune cell
      attachment was increased 1.6-fold when tumor necrosis factor (TNF)-alpha
      stimulated HSVEC were exposed to coronary artery flow in place of physiological
      venous flow and 1.9-fold higher compared with attachment to cytokine-stimulated
      HCAEC exposed to coronary artery flow. This was associated with increased
      concentrations of soluble E-selectin, VCAM-1, and ICAM-1 in supernatants of HSVEC
      exposed to coronary artery flow compared with HCAEC exposed to the same flow
      pattern. Venous and coronary artery flow both increased TNF-alpha-induced E
      selectin and ICAM-1 expression on HSVEC, but only coronary artery flow increased
      VCAM-1 expression. In marked contrast to HSVEC, venous and coronary artery flow
      attenuated TNF-alpha-induced E-selectin and VCAM-1 expression on HCAEC, whereas
      coronary artery flow further induced ICAM-1 on cytokine-stimulated HCAEC. With
      the exception of cytokine-induced ICAM-1, adhesion molecule expression on HSVEC
      exposed to coronary artery flow exceeded expression on HCAEC. Thus ICAM-1
      expression involves complex flow-dependent and -independent pathways with marked
      dissimilarities between the two endothelial cell types studied. Interestingly,
      Kruppel-like factor (KLF) 4 overexpression in HCAEC and HSVEC significantly
      reduced TNF-alpha-induced E-selectin and VCAM-1 expression in static conditions,
      while ICAM-1 expression remained constant. Furthermore, both flow patterns
      induced KLF2 and KLF4 expression in HCAEC and HSVEC. Venous and coronary artery
      flow differentially influence endothelial adhesion molecule and transcription
      factor expression, depending on the vascular bed of origin. Differences in
      adhesion molecule expression and subsequent immune cell adhesion between HSVEC
      and HCAEC may contribute to different susceptibility to pathological conditions.

PMID- 17209005
TI  - Polymorphic ventricular tachycardia and abnormal Ca2+ handling in very-long-chain
      acyl-CoA dehydrogenase null mice.
AB  - Patients with mutations in the mitochondrial very-long-chain acyl-CoA
      dehydrogenase (VLCAD) gene are at risk for cardiomyopathy, myocardial
      dysfunction, ventricular tachycardia (VT), and sudden cardiac death. The
      mechanism is not known. Here we report a novel mechanism of VT in mice lacking
      VLCAD (VLCAD(-/-)). These mice exhibited polymorphic VT and increased incidence
      of VT after isoproterenol infusion. Polymorphic VT was induced in 10 out of 12
      VLCAD(-/-) mice (83%) when isoproterenol was used. One out of 10 VLCAD(-/-) mice
      with polymorphic VT had VT with the typical bidirectional morphology. At the
      molecular level, VLCAD(-/-) cardiomyocytes showed increased levels of cardiac
      ryanodine receptor 2, phospholamban, and calsequestrin with increased
      [(3)H]ryanodine binding in heart microsomes. At the single cardiomyocyte level,
      VLCAD(-/-) cardiomyocytes showed significant increase in diastolic indo 1 and
      fura 2 fluorescence, with increased Ca(2+) transient amplitude. These changes
      were associated with altered Ca(2+) dynamics, to include: faster sarcomere
      contraction, larger time derivative of the upstroke, and shorter time-to-minimum
      sarcomere length compared with VLCAD(+/+) control cells. The L-type Ca(2+)
      current characteristics were not different under voltage-clamp conditions in the
      two VLCAD genotypes. Sarcoplasmic reticulum Ca(2+) load measured as normalized
      integrated Na(+)/Ca(2+) exchange current after rapid caffeine application was
      increased by 48% in VLCAD(-/-) cells. We conclude that intracellular Ca(2+)
      handling represents a possible molecular mechanism of arrhythmias in mice and
      perhaps in VLCAD-deficient humans.

PMID- 17209006
TI  - PKC-alpha and TAK-1 are intermediates in the activation of c-Jun NH2-terminal
      kinase by hypoxia-reoxygenation.
AB  - c-Jun NH(2)-terminal kinase (JNK), a member of the MAPK family of protein
      kinases, is a stress-response kinase that is activated by proinflammatory
      cytokines and growth factors coupled to membrane receptors or through nonreceptor
      pathways by stimuli such as heat shock, UV irradiation, protein synthesis
      inhibitors, and conditions that elevate the levels of reactive oxygen
      intermediates (ROI). Ischemia followed by reperfusion or hypoxia with
      reoxygenation represents a condition of high oxidative stress where JNK
      activation is associated with elevated ROI. We recently demonstrated that the
      activation of JNK by this condition is initiated by ROI generated by
      mitochondrial electron transport and involves sequential activation of the
      proline-rich kinase 2 and the small GTP-binding factors Rac-1 and Cdc42. Here we
      present evidence that protein kinase C (PKC) and transforming growth factor-beta
      activated kinase-1 (TAK-1) are also components of this pathway. Inhibition of PKC
      with the broad-range inhibitor calphostin C, the PKC-alpha/beta-selective
      inhibitor Go9367, or adenovirus-expressing dominant-negative PKC-alpha blocked
      the phosphorylation of proline-rich kinase 2 and JNK. Reoxygenation activated the
      mitogen-activated protein kinase kinase kinase, TAK-1, and promoted the formation
      of a complex containing Rac-1, TAK-1, and JNK but not apoptosis-stimulating
      kinase-1 or p21-activated kinase-1, which was detected within the first 10 min of
      reoxygenation. These results identify two new components, PKC and TAK-1, that
      have not been previously described in this signaling pathway.

PMID- 17209007
TI  - Electroacupuncture decreases the susceptibility to ventricular tachycardia in
      conscious rats by reducing cardiac metabolic demand.
AB  - Reperfusion after a brief period of cardiac ischemia can lead to potentially
      lethal arrhythmias. Clinical observations and experimental work with animals
      suggest that acupuncture may have therapeutic effects for individuals with
      coronary heart disease, certain arrhythmias, and myocardial ischemia. Therefore,
      we tested the hypothesis that electroacupuncture reduces the susceptibility to
      ischemia-reperfusion-mediated ventricular tachyarrhythmias. To test this
      hypothesis, we measured the susceptibility to ventricular tachyarrhythmias
      produced by 3 min of occlusion and reperfusion of the left main coronary artery
      in conscious rats under two experimental conditions: 1) control and 2) with
      electroacupuncture. Acupuncture was simulated by electrically stimulating the
      median nerves, corresponding to the Jianshi-Neiguan [pericardial meridian (P) 5
      6] acupoints. Results document a significantly lower incidence of ventricular
      tachyarrhythmias with electroacupuncture (2 of 8, 25%) relative to control (14 of
      14, 100%) rats. The decreased susceptibility to tachyarrhythmias with
      electroacupuncture was associated with a reduced cardiac metabolic demand (lower
      rate-pressure product and ST-segment elevation) during ischemia.

PMID- 17209008
TI  - Metabolism of adrenic acid to vasodilatory 1alpha,1beta-dihomo
      epoxyeicosatrienoic acids by bovine coronary arteries.
AB  - Adrenic acid (docosatetraenoic acid), an abundant fatty acid in the vasculature,
      is produced by a two-carbon chain elongation of arachidonic acid. Despite its
      abundance and similarity to arachidonic acid, little is known about its role in
      the regulation of vascular tone. Gas chromatography/mass spectrometric analysis
      of bovine coronary artery and endothelial cell lysates revealed arachidonic acid
      concentrations of 2.06 +/- 0.01 and 6.18 +/- 0.60 microg/mg protein and adrenic
      acid concentrations of 0.29 +/- 0.01 and 1.56 +/- 0.16 microg/mg protein,
      respectively. In bovine coronary arterial rings preconstricted with the
      thromboxane mimetic U-46619, adrenic acid (10(-9)-10(-5) M) induced concentration
      related relaxations (maximal relaxation = 83 +/- 4%) that were similar to
      arachidonic acid relaxations. Adrenic acid relaxations were blocked by
      endothelium removal and the K(+) channel inhibitor, iberiotoxin (100 nM), and
      inhibited by the cyclooxygenase inhibitor, indomethacin (10 microM, maximal
      relaxation = 53 +/- 4%), and the cytochrome P-450 inhibitor, miconazole (10
      microM, maximal relaxation = 52 +/- 5%). Reverse-phase HPLC and liquid
      chromatography/mass spectrometry isolated and identified numerous adrenic acid
      metabolites from coronary arteries including dihomo (DH)-epoxyeicosatrienoic
      acids (EETs) and DH-prostaglandins. DH-EET [16,17-, 13,14-, 10,11-, and 7,8- (10(
      9)-10(-5) M)] induced similar concentration-related relaxations (maximal
      relaxations averaged 83 +/- 3%). Adrenic acid (10(-6) M) and DH-16,17-EET (10(-6)
      M) hyperpolarized coronary arterial smooth muscle. DH-16,17-EET (10(-8)-10(-6) M)
      activated iberiotoxin-sensitive, whole cell K(+) currents of isolated smooth
      muscle cells. Thus, in bovine coronary arteries, adrenic acid causes endothelium
      dependent relaxations that are mediated by cyclooxygenase and cytochrome P-450
      metabolites. The adrenic acid metabolite, DH-16,17-EET, activates smooth muscle
      K(+) channels to cause hyperpolarization and relaxation. Our results suggest a
      role of adrenic acid metabolites, specifically, DH-EETs as endothelium-derived
      hyperpolarizing factors in the coronary circulation.

PMID- 17209009
TI  - Effects of biaxial stretch on arteriolar function in vitro.
AB  - Mounting evidence suggests that the normal biomechanical state of arteries may
      include a nearly equibiaxial intramural stress and that arteries tend to undergo
      rapid and dramatic remodeling when perturbed from this normal state. Technical
      developments since the early 1980s have enabled in vitro (acute) and ex vivo
      (chronic culture) study of isolated, perfused microvessels, and it is clear that
      these vessels share many functional similarities with arteries. To date, however,
      there has been no systematic study of the effects of in-plane biaxial loading on
      the biomechanical behavior of arterioles. Here we describe a modification to a
      prior in vitro arterial test system that allowed us to investigate the role of
      altered axial stretch on the passive, myogenic, and norepinephrine-stimulated
      biaxial behavior of isolated rat cremaster arterioles. We show that axial
      stretches from 85% to 110% of values often used in the laboratory and consistent
      with those normally experienced in situ induce modest changes in the measured
      mean circumferential and axial stress-stretch behavior and in measures of
      distensibility and myogenic index. Nevertheless, altered axial stretch has a
      dramatic effect on the biaxial state of stress, and nearly equibiaxial stresses
      occur at axial stretches larger than those typically used in isolated arteriole
      studies. This finding is consistent with estimates of material and functional
      behavior in arterioles and suggests that long-term ex vivo studies, wherein
      vessel growth and remodeling are critical, should be performed at higher axial
      lengths than have been used during most prior in vitro tests.

PMID- 17209010
TI  - Controlled expression of transgenes introduced by in vivo electroporation.
AB  - In vivo electroporation is a powerful technique for the introduction of genes
      into organisms. Temporal and spatial regulation of expression of introduced
      genes, or of RNAi, would further enhance the utility of this method. Here we
      demonstrate conditional regulation of gene expression from electroporated
      plasmids in the postnatal rat retina and the embryonic mouse brain. For temporal
      regulation, Cre/loxP-mediated inducible expression vectors were used in
      combination with a vector expressing a conditionally active form of Cre
      recombinase, which is activated by 4-hydroxytamoxifen. Onset of gene expression
      was regulated by the timing of 4-hydroxytamoxifen administration. For spatial
      regulation, transgenes were expressed by using promoters specific for rod
      photoreceptors, bipolar cells, amacrine cells, Muller glia or progenitor cells.
      Combinations of these constructs will facilitate a variety of experiments,
      including cell-type-specific gene misexpression, conditional RNAi, and fate
      mapping of progenitor and precursor cells.

PMID- 17209011
TI  - Epigenetic memory at malaria virulence genes.
AB  - During its red blood cell stage, the malaria parasite Plasmodium falciparum can
      switch its variant surface proteins (P. falciparum erythrocyte membrane protein
      1) to evade the host immune response. The var gene family encodes P. falciparum
      erythrocyte membrane protein 1, different versions of which have unique binding
      specificities to various human endothelial surface molecules. Individual
      parasites each contain approximately 60 var genes at various locations within
      their chromosomes; however, parasite isolates contain different complements of
      var genes, thus, the gene family is enormous with a virtually unlimited number of
      members. A single var gene is expressed by each parasite in a mutually exclusive
      manner. We report that control of var gene transcription and antigenic variation
      is associated with a chromatin memory that includes methylation of histone H3 at
      lysine K9 as an epigenetic mark. We also discuss how gene transcription memory
      may affect the mechanism of pathogenesis and immune evasion.

PMID- 17209012
TI  - HIV-susceptible transgenic rats allow rapid preclinical testing of antiviral
      compounds targeting virus entry or reverse transcription.
AB  - The current testing of anti-HIV drugs is hampered by the lack of a small animal
      that is readily available and easy to handle; can be infected systemically with
      HIV type 1 (HIV-1); harbors the major HIV-1 target cells in a physiological
      frequency, organ distribution, and activation state; and is established as a
      pharmacological model. Here, we explored the potential of outbred Sprague-Dawley
      rats that transgenically express the HIV-1 receptor complex on CD4 T cells and
      macrophages as a model for the preclinical evaluation of inhibitors targeting
      virus entry or reverse transcription. The concentrations of the peptidic fusion
      inhibitor enfuvirtide or the nonnucleoside reverse transcriptase inhibitor
      efavirenz required to inhibit HIV-1 infection of cultured primary CD4 T cells and
      macrophages from human CD4 and CCR5-transgenic rats differed by no more than 3
      fold from those required for human reference cultures. Prophylactic treatment of
      double-transgenic rats with a weight-adapted pediatric dosing regimen for either
      enfuvirtide (s.c., twice-daily) or efavirenz (oral, once-daily) achieved a 92.5%
      or 98.8% reduction, respectively, of the HIV-1 cDNA load in the spleen 4 days
      after i.v. HIV-1 challenge. Notably, a once-daily dosing regimen for enfuvirtide
      resulted in a approximately 5-fold weaker inhibition of infection, unmasking the
      unfavorable pharmacokinetic characteristics of the synthetic peptide in the
      context of an efficacy trial. This work provides proof of principle that HIV
      susceptible transgenic rats can allow a rapid and predictive preclinical
      evaluation of the inhibitory potency and of the pharmacokinetic properties of
      antiviral compounds targeting early steps in the HIV replication cycle.

PMID- 17209013
TI  - Role of SUMO in the dynamics of telomere maintenance in fission yeast.
AB  - The sheltering of chromosome ends from illegitimate DNA repair reactions and
      telomere length homeostasis are critical for preserving genomic integrity.
      Growing evidence implicates covalent protein modification by SUMO (small
      ubiquitin-like modifier) (sumoylation) in the regulation of numerous DNA
      transactions, including DNA repair and transcription, as well as heterochromatin
      formation and maintenance. We have recently shown that fission yeast Pli1p is a
      SUMO E3 ligase and that pli1 mutants, which are impaired for global sumoylation,
      are viable, but exhibit de-regulated homologous recombination and marked defects
      in chromosome segregation and centromeric silencing, as well as a consistent
      increase in telomere length. In this work, we explore the mechanisms underlying
      sumoylation-dependent telomere maintenance. We show that Pli1p, but not the
      related Nse2p, is the principal SUMO E3 ligase enzyme involved. Using both a pli1
      mutation and a physiological "knockdown" of sumoylation, achieved by inducible
      expression of a dominant negative form of the conjugating enzyme Ubc9p, we
      further show that telomere lengthening induced by lack of sumoylation is not due
      to unscheduled telomere-telomere recombination. Instead, sumoylation increases
      telomerase activity, therefore suggesting that this modification controls the
      activity of a positive or negative regulator of telomerase.

PMID- 17209014
TI  - Photoselected electron transfer pathways in DNA photolyase.
AB  - Cyclobutane dimer photolyases are proteins that bind to UV-damaged DNA containing
      cyclobutane pyrimidine dimer lesions. They repair these lesions by photo-induced
      electron transfer. The electron donor cofactor of a photolyase is a two-electron
      reduced flavin adenine dinucleotide (FADH(-)). When FADH(-) is photo-excited, it
      transfers an electron from an excited pi --> pi* singlet state to the pyrimidine
      dimer lesion of DNA. We compute the lowest excited singlet states of FADH(-)
      using ab initio (time-dependent density functional theory and time-dependent
      Hartree-Fock), and semiempirical (INDO/S configuration interaction) methods. The
      calculations show that the two lowest pi --> pi* singlet states of FADH(-) are
      localized on the side of the flavin ring that is proximal to the dimer lesion of
      DNA. For the lowest-energy donor excited state of FADH(-), we compute the
      conformationally averaged electronic coupling to acceptor states of the thymine
      dimer. The coupling calculations are performed at the INDO/S level, on donor
      acceptor cofactor conformations obtained from molecular dynamics simulations of
      the solvated protein with a thymine dimer docked in its active site. These
      calculations demonstrate that the localization of the (1)FADH(-)* donor state on
      the flavin ring enhances the electronic coupling between the flavin and the dimer
      by permitting shorter electron-transfer pathways to the dimer that have single
      through-space jumps. Therefore, in photolyase, the photo-excitation itself
      enhances the electron transfer rate by moving the electron towards the dimer.

PMID- 17209015
TI  - Evidence for type III restriction and modification systems in Mycoplasma
      pulmonis.
AB  - Mycoplasma pulmonis possesses a cassette of genes that are predicted to code for
      type III restriction and modification (R-M) enzymes. Transposon disruption of a
      gene predicted to code for the endonuclease subunit of the enzyme resulted in
      loss of R-M activity. Genomic data indicate that the cassette was acquired by
      horizontal gene transfer and possibly located on a mobile element.

PMID- 17209016
TI  - Genome sequence and analysis of the soil cellulolytic actinomycete Thermobifida
      fusca YX.
AB  - Thermobifida fusca is a moderately thermophilic soil bacterium that belongs to
      Actinobacteria. It is a major degrader of plant cell walls and has been used as a
      model organism for the study of secreted, thermostable cellulases. The complete
      genome sequence showed that T. fusca has a single circular chromosome of
      3,642,249 bp predicted to encode 3,117 proteins and 65 RNA species with a coding
      density of 85%. Genome analysis revealed the existence of 29 putative glycoside
      hydrolases in addition to the previously identified cellulases and xylanases. The
      glycosyl hydrolases include enzymes predicted to exhibit mainly dextran/starch-
      and xylan-degrading functions. T. fusca possesses two protein secretion systems:
      the sec general secretion system and the twin-arginine translocation system.
      Several of the secreted cellulases have sequence signatures indicating their
      secretion may be mediated by the twin-arginine translocation system. T. fusca has
      extensive transport systems for import of carbohydrates coupled to
      transcriptional regulators controlling the expression of the transporters and
      glycosylhydrolases. In addition to providing an overview of the physiology of a
      soil actinomycete, this study presents insights on the transcriptional regulation
      and secretion of cellulases which may facilitate the industrial exploitation of
      these systems.

PMID- 17209017
TI  - Role of an FtsK-like protein in genetic stability in Streptomyces coelicolor
      A3(2).
AB  - Streptomyces coelicolor A3(2) does not have a canonical cell division cycle
      during most of its complex life cycle, yet it contains a gene (ftsK(SC)) encoding
      a protein similar to FtsK, which couples the completion of cell division and
      chromosome segregation in unicellular bacteria such as Escherichia coli. Here, we
      show that various constructed ftsK(SC) mutants all grew apparently normally and
      sporulated but upon restreaking gave rise to many aberrant colonies and to high
      frequencies of chloramphenicol-sensitive mutants, a phenotype previously
      associated with large terminal deletions from the linear chromosome. Indeed, most
      of the aberrant colonies had lost large fragments near one or both chromosomal
      termini, as if chromosome ends had failed to reach their prespore destination
      before the closure of sporulation septa. A constructed FtsK(SC)-enhanced green
      fluorescent protein fusion protein was particularly abundant in aerial hyphae,
      forming distinctive complexes before localizing to each sporulation septum,
      suggesting a role for FtsK(SC) in chromosome segregation during sporulation. Use
      of a fluorescent reporter showed that when ftsK(SC) was deleted, several spore
      compartments in most spore chains failed to express the late-sporulation-specific
      sigma factor gene sigF, even though they contained chromosomal DNA. This
      suggested that sigF expression is autonomously activated in each spore
      compartment in response to completion of chromosome transfer, which would be a
      previously unknown checkpoint for late-sporulation-specific gene expression.
      These results provide new insight into the genetic instability prevalent among
      streptomycetes, including those used in the industrial production of antibiotics.

PMID- 17209018
TI  - Sinorhizobium meliloti SyrA mediates the transcriptional regulation of genes
      involved in lipopolysaccharide sulfation and exopolysaccharide biosynthesis.
AB  - Sinorhizobium meliloti is a gram-negative soil bacterium found either in free
      living form or as a nitrogen-fixing endosymbiont of leguminous plants such as
      Medicago sativa (alfalfa). S. meliloti synthesizes an unusual sulfate-modified
      form of lipopolysaccharide (LPS). A recent study reported the identification of a
      gene, lpsS, which encodes an LPS sulfotransferase activity in S. meliloti.
      Mutants bearing a disrupted version of lpsS exhibit an altered symbiosis, in that
      they elicit more nodules than wild type. However, under free-living conditions,
      the lpsS mutant displayed no change in LPS sulfation. These data suggest that the
      expression of lpsS is differentially regulated, such that it is transcriptionally
      repressed during free-living conditions but upregulated during symbiosis. Here, I
      show that the expression of lpsS is upregulated in strains that constitutively
      express the symbiotic regulator SyrA. SyrA is a small protein that lacks an
      apparent DNA binding domain and is predicted to be located in the cytoplasmic
      membrane yet is sufficient to upregulate lpsS transcription. Furthermore, SyrA
      can mediate the transcriptional upregulation of exo genes involved in the
      biosynthesis of the symbiotic exopolysaccharide succinoglycan. The SyrA-mediated
      transcriptional upregulation of lpsS and exo transcription is blocked in mutants
      harboring a mutation in chvI, which encodes the response regulator of a conserved
      two-component system. Thus, SyrA likely acts indirectly to promote
      transcriptional upregulation of lpsS and exo genes through a mechanism that
      requires the ExoS/ChvI two-component system.

PMID- 17209019
TI  - Metabolism of linoleic acid by human gut bacteria: different routes for
      biosynthesis of conjugated linoleic acid.
AB  - A survey of 30 representative strains of human gram-positive intestinal bacteria
      indicated that Roseburia species were among the most active in metabolizing
      linoleic acid (cis-9,cis-12-18:2). Different Roseburia spp. formed either
      vaccenic acid (trans-11-18:1) or a 10-hydroxy-18:1; these compounds are
      precursors of the health-promoting conjugated linoleic acid cis-9,trans-11-18:2
      in human tissues and the intestine, respectively.

PMID- 17209020
TI  - Enzyme diversity of the cellulolytic system produced by Clostridium
      cellulolyticum explored by two-dimensional analysis: identification of seven
      genes encoding new dockerin-containing proteins.
AB  - The enzyme diversity of the cellulolytic system produced by Clostridium
      cellulolyticum grown on crystalline cellulose as a sole carbon and energy source
      was explored by two-dimensional electrophoresis. The cellulolytic system of C.
      cellulolyticum is composed of at least 30 dockerin-containing proteins
      (designated cellulosomal proteins) and 30 noncellulosomal components. Most of the
      known cellulosomal proteins, including CipC, Cel48F, Cel8C, Cel9G, Cel9E, Man5K,
      Cel9M, and Cel5A, were identified by using two-dimensional Western blot analysis
      with specific antibodies, whereas Cel5N, Cel9J, and Cel44O were identified by
      using N-terminal sequencing. Unknown enzymes having carboxymethyl cellulase or
      xylanase activities were detected by zymogram analysis of two-dimensional gels.
      Some of these enzymes were identified by N-terminal sequencing as homologs of
      proteins listed in the NCBI database. Using Trap-Dock PCR and DNA walking, seven
      genes encoding new dockerin-containing proteins were cloned and sequenced. Some
      of these genes are clustered. Enzymes encoded by these genes belong to glycoside
      hydrolase families GH2, GH9, GH10, GH26, GH27, and GH59. Except for members of
      family GH9, which contains only cellulases, the new modular glycoside hydrolases
      discovered in this work could be involved in the degradation of different
      hemicellulosic substrates, such as xylan or galactomannan.

PMID- 17209022
TI  - CadC has a global translational effect during acid adaptation in Salmonella
      enterica serovar Typhimurium.
AB  - In Salmonella enterica serovar Typhimurium, the membrane-localized CadC is a
      transcriptional activator of the cadBA operon, which contributes to the acid
      tolerance response. Unlike in Escherichia coli, in which transcription of cadC is
      constitutive, in S. enterica serovar Typhimurium cadC expression is induced by
      low pH and lysine. Inactivation of cadC suppresses the acid-sensitive phenotype
      of a cadA mutation, suggesting the existence of other CadC-dependent genes in
      addition to the cadBA operon. Using a proteomic approach, we identified 8 of the
      putative CadC-induced proteins and 15 of the putative CadC-repressed proteins.
      The former include porin proteins OmpC and OmpF. The latter include proteins
      involved in glycolysis, energy production, and stress tolerance. To better
      understand the altered levels of OmpC and OmpF, we compared expression of ompR in
      S. enterica serovar Typhimurium wild-type and cadC mutant strains and determined
      that CadC exerted a negative influence on ompR transcription. Taken together, our
      findings strongly suggest that CadC may be a global regulator involved in the
      OmpR regulatory system during acid adaptation.

PMID- 17209021
TI  - Genes required for glycolipid synthesis and lipoteichoic acid anchoring in
      Staphylococcus aureus.
AB  - Staphylococcus aureus lipoteichoic acid (LTA) is composed of a linear 1,3-linked
      polyglycerolphosphate chain and is tethered to the bacterial membrane by a
      glycolipid (diglucosyl-diacylglycerol [Glc2-DAG]). Glc2-DAG is synthesized in the
      bacterial cytoplasm by YpfP, a processive enzyme that transfers glucose to
      diacylglycerol (DAG), using UDP-glucose as its substrate. Here we present
      evidence that the S. aureus alpha-phosphoglucomutase (PgcA) and UTP:alpha-glucose
      1-phosphate uridyltransferase (GtaB) homologs are required for the synthesis of
      Glc2-DAG. LtaA (lipoteichoic acid protein A), a predicted membrane permease whose
      structural gene is located in an operon with ypfP, is not involved in Glc2-DAG
      synthesis but is required for synthesis of glycolipid-anchored LTA. Our data
      suggest a model in which LtaA facilitates the transport of Glc2-DAG from the
      inner (cytoplasmic) leaflet to the outer leaflet of the plasma membrane,
      delivering Glc2-DAG as a substrate for LTA synthesis, thereby generating
      glycolipid-anchored LTA. Glycolipid anchoring of LTA appears to play an important
      role during infection, as S. aureus variants lacking ltaA display defects in the
      pathogenesis of animal infections.

PMID- 17209023
TI  - Reassessment of the late steps of coenzyme B12 synthesis in Salmonella enterica:
      evidence that dephosphorylation of adenosylcobalamin-5'-phosphate by the CobC
      phosphatase is the last step of the pathway.
AB  - We report that cobC strains of Salmonella enterica serovar Typhimurium are
      impaired in the ability to salvage cobyric acid (Cby), a de novo corrin ring
      biosynthetic intermediate, under aerobic growth conditions. In vivo and in vitro
      evidence support the conclusion that this new phenotype of cobC strains is due to
      the inability of serovar Typhimurium to dephosphorylate adenosylcobalamin-5'
      phosphate (AdoCbl-5'-P), the product of the condensation of alpha-ribazole-5'
      phosphate (alpha-RP) and adenosylcobinamide-GDP by the AdoCbl-5'-P synthase
      (CobS, EC 2.7.8.26) enzyme. Increased flux through the 5,6-dimethylbenzimidazole
      and cobinamide (Cbi) activation branches of the nucleotide loop assembly pathway
      in cobC strains restored AdoCbl-5'-P synthesis from Cby in a cobC strain. The
      rate of the CobS-catalyzed reaction was at least 2 orders of magnitude higher
      with alpha-RP than with alpha-ribazole as substrate. On the basis of the data
      reported herein, we conclude that removal of the phosphoryl group from AdoCbl-5'
      P is the last step in AdoCbl biosynthesis in serovar Typhimurium and that the
      reaction is catalyzed by the AdoCbl-5'-P phosphatase (CobC) enzyme. Explanations
      for the correction of the Cby salvaging phenotype are discussed.

PMID- 17209025
TI  - The cymA gene, encoding a tetraheme c-type cytochrome, is required for arsenate
      respiration in Shewanella species.
AB  - In Shewanella sp. strain ANA-3, utilization of arsenate as a terminal electron
      acceptor is conferred by a two-gene operon, arrAB, which lacks a gene encoding a
      membrane-anchoring subunit for the soluble ArrAB protein complex. Analysis of the
      genome sequence of Shewanella putrefaciens strain CN-32 showed that it also
      contained the same arrAB operon with 100% nucleotide identity. Here, we report
      that CN-32 respires arsenate and that this metabolism is dependent on arrA and an
      additional gene encoding a membrane-associated tetraheme c-type cytochrome, cymA.
      Deletion of cymA in ANA-3 also eliminated growth on and reduction of arsenate.
      The DeltacymA strains of CN-32 and ANA-3 negatively affected the reduction of
      Fe(III) and Mn(IV) but not growth on nitrate. Unlike the CN-32 DeltacymA strain,
      growth on fumarate was absent in the DeltacymA strain of ANA-3. Both homologous
      and heterologous complementation of cymA in trans restored growth on arsenate in
      DeltacymA strains of both CN-32 and ANA-3. Transcription patterns of cymA showed
      that it was induced under anaerobic conditions in the presence of fumarate and
      arsenate. Nitrate-grown cells exhibited the greatest level of cymA expression in
      both wild-type strains. Lastly, site-directed mutagenesis of the first Cys to Ser
      in each of the four CXXCH c-heme binding motifs of the CN-32 CymA nearly
      eliminated growth on and reduction of arsenate. Together, these results indicate
      that the biochemical mechanism of arsenate respiration and reduction requires the
      interactions of ArrAB with a membrane-associated tetraheme cytochrome, which in
      the non-arsenate-respiring Shewanella species Shewanella oneidensis strain MR-1,
      has pleiotropic effects on Fe(III), Mn(IV), dimethyl sulfoxide, nitrate, nitrite,
      and fumarate respiration.

PMID- 17209024
TI  - A type IV-secretion-like system is required for conjugative DNA transport of
      broad-host-range plasmid pIP501 in gram-positive bacteria.
AB  - Plasmid pIP501 has a very broad host range for conjugative transfer among a wide
      variety of gram-positive bacteria and gram-negative Escherichia coli.
      Functionality of the pIP501 transfer (tra) genes in E. coli was proven by pIP501
      retrotransfer to Enterococcus faecalis (B. Kurenbach, C. Bohn, J. Prabhu, M.
      Abudukerim, U. Szewzyk, and E. Grohmann, Plasmid 50:86-93, 2003). The 15 pIP501
      tra genes are organized in a single operon (B. Kurenbach, J. Kopec, M. Magdefrau,
      K. Andreas, W. Keller, C. Bohn, M. Y. Abajy, and E. Grohmann, Microbiology
      152:637-645, 2006). The pIP501 tra operon is negatively autoregulated at the
      transcriptional level by the conjugative DNA relaxase TraA. Three of the 15
      pIP501-encoded Tra proteins show significant sequence similarity to the
      Agrobacterium type IV secretion system proteins VirB1, VirB4, and VirD4. Here we
      report a comprehensive protein-protein interaction map of all of the pIP501
      encoded Tra proteins determined by the yeast two-hybrid assay. Most of the
      interactions were verified in vitro by isolation of the protein complexes with
      pull-down assays. In conjunction with known or postulated functions of the pIP501
      encoded Tra proteins and computer-assisted prediction of their cellular location,
      we propose a model for the first type IV-secretion-like system encoded by a
      conjugative plasmid from gram-positive bacteria.

PMID- 17209026
TI  - The novel transcription factor SgrR coordinates the response to glucose-phosphate
      stress.
AB  - SgrR is the first characterized member of a family of bacterial transcription
      factors containing an N-terminal DNA binding domain and a C-terminal solute
      binding domain. Previously, we reported genetic evidence that SgrR activates the
      divergently transcribed gene sgrS, which encodes a small RNA required for
      recovery from glucose-phosphate stress. In this study, we examined the regulation
      of sgrR expression and found that SgrR negatively autoregulates its own
      transcription in the presence and absence of stress. An SgrR binding site in the
      sgrR-sgrS intergenic region is required in vivo for both SgrR-dependent
      activation of sgrS and autorepression of sgrR. Purified SgrR binds specifically
      to sgrS promoter DNA in vitro; a mutation in the site required for in vivo
      activation and autorepression abrogates in vitro SgrR binding. A plasmid library
      screen identified clones that alter expression of a P(sgrS)-lacZ fusion; some act
      by titrating endogenous SgrR. The yfdZ gene, encoding a putative
      aminotransferase, was identified in this screen; the yfdZ promoter contains an
      SgrR binding site, and transcriptional fusions indicate that yfdZ is activated by
      SgrR. Clones containing mlc, which encodes a glucose-specific repressor protein,
      also downregulate P(sgrS)-lacZ. The mlc clones do not appear to titrate the SgrR
      protein, indicating that Mlc affects sgrS expression by an alternative mechanism.

PMID- 17209027
TI  - Presence or absence of lipopolysaccharide O antigens affects type III secretion
      by Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is one of the major causative agents of mortality and
      morbidity in hospitalized patients due to a multiplicity of virulence factors
      associated with both chronic and acute infections. Acute P. aeruginosa infection
      is primarily mediated by planktonic bacteria expressing the type III secretion
      system (TTSS), a surface-attached needle-like complex that injects cytotoxins
      directly into eukaryotic cells, causing cellular damage. Lipopolysaccharide (LPS)
      is the principal surface-associated virulence factor of P. aeruginosa. This
      molecule is known to undergo structural modification (primarily alterations in
      the A- and B-band O antigen) in response to changes in the mode of life (e.g.,
      from biofilm to planktonic). Given that LPS exhibits structural plasticity, we
      hypothesized that the presence of LPS lacking O antigen would facilitate
      eukaryotic intoxication and that a correlation between the LPS O-antigen serotype
      and TTSS-mediated cytotoxicity would exist. Therefore, strain PAO1 (A+ B+ O
      antigen serotype) and isogenic mutants with specific O-antigen defects (A+ B-, A-
      B+, and A- B-) were examined for TTSS expression and cytotoxicity. A strong
      association existed in vitro between the absence of the large, structured B-band
      O antigen and increased cytotoxicity of these strains. In vivo, all three LPS
      mutant strains demonstrated significantly increased lung injury compared to PAO1.
      Clinical strains lacking the B-band O antigen also demonstrated increased TTSS
      secretion. These results suggest the existence of a cooperative association
      between LPS O-antigen structure and the TTSS in both laboratory and clinical
      isolates of P. aeruginosa.

PMID- 17209028
TI  - S-layer anchoring and localization of an S-layer-associated protease in
      Caulobacter crescentus.
AB  - The S-layer of the gram-negative bacterium Caulobacter crescentus is composed of
      a single protein, RsaA, that is secreted and assembled into a hexagonal
      crystalline array that covers the organism. Despite the widespread occurrence of
      comparable bacterial S-layers, little is known about S-layer attachment to cell
      surfaces, especially for gram-negative organisms. Having preliminary indications
      that the N terminus of RsaA anchors the monomer to the cell surface, we developed
      an assay to distinguish direct surface attachment from subunit-subunit
      interactions where small RsaA fragments are incubated with S-layer-negative cells
      to assess the ability of the fragments to reattach. In doing so, we found that
      the RsaA anchoring region lies in the first approximately 225 amino acids and
      that this RsaA anchoring region requires a smooth lipopolysaccharide species
      found in the outer membrane. By making mutations at six semirandom sites, we
      learned that relatively minor perturbations within the first approximately 225
      amino acids of RsaA caused loss of anchoring. In other studies, we confirmed that
      only this N-terminal region has a direct role in S-layer anchoring. As a by
      product of the anchoring studies, we discovered that Sap, the C. crescentus S
      layer-associated protease, recognized a cleavage site in the truncated RsaA
      fragments that is not detected by Sap in full-length RsaA. This, in turn, led to
      the discovery that Sap was an extracellular membrane-bound protease, rather than
      intracellular, as previously proposed. Moreover, Sap was secreted to the cell
      surface primarily by the S-layer type I secretion apparatus.

PMID- 17209029
TI  - A possible heterodimeric prophage-like element in the genome of the insect
      endosymbiont Sodalis glossinidius.
AB  - Extrachromosomal element pSOG3 (52,162 nucleotides) in the genome of Sodalis
      glossinidius contains redundant phage-related gene pairs, indicating that it may
      have been formed by the fusion of two ancestral phage genomes followed by gene
      degradation. We suggest that pSOG3 is a prophage that has undergone genome
      degeneration accompanying host adaptation to symbiosis.

PMID- 17209031
TI  - Biosynthesis of the thioquinolobactin siderophore: an interesting variation on
      sulfur transfer.
AB  - The thioquinolobactin siderophore from Pseudomonas fluorescens ATCC 17400
      utilizes a variation of the sulfur transfer chemistry found in thiamine and
      molydobterin biosynthesis. A JAMM motif protein cleaves the C-terminal amino acid
      residues following a diglycine moiety on a small sulfur carrier protein, and the
      modified C terminus is activated and sulfurylated, forming a thiocarboxylate.

PMID- 17209030
TI  - Amplification of lac cannot account for adaptive mutation to Lac+ in Escherichia
      coli.
AB  - When the Lac- strain of Escherichia coli, FC40, is incubated with lactose as its
      sole carbon and energy source, Lac+ revertants arise at a constant rate, a
      phenomenon known as adaptive mutation. Two alternative models for adaptive
      mutation have been proposed: (i) recombination-dependent mutation, which
      specifies that recombination occurring in nongrowing cells stimulates error-prone
      DNA synthesis, and (ii) amplification-dependent mutation, which specifies that
      amplification of the lac region and growth of the amplifying cells creates enough
      DNA replication to produce mutations at the normal rate. Here, we examined
      several of the predictions of the amplification-dependent mutation model and
      found that they are not fulfilled. First, inhibition of adaptive mutation by a
      gene that is toxic when overexpressed does not depend on the proximity of the
      gene to lac. Second, mutation at a second locus during selection for Lac+
      revertants is also independent of the proximity of the locus to lac. Third,
      mutation at a second locus on the episome occurs even when the lac allele under
      selection is on the chromosome. Our results support the hypothesis that most Lac+
      mutants that appear during lactose selection are true revertants that arise in a
      single step from Lac- cells, not from a population of growing or amplifying
      precursor cells.

PMID- 17209032
TI  - The lysine decarboxylase CadA protects Escherichia coli starved of phosphate
      against fermentation acids.
AB  - Conflicting results have been reported for the rate and extent of cell death
      during a prolonged stationary phase. It is shown here that the viability of wild
      type cells (MG1655) could decrease >or=10(8)-fold between days 1 and 14 and
      between days 1 and 6 of incubation under aerobic and anaerobic phosphate (P(i))
      starvation conditions, respectively, whereas the cell viability decreased
      moderately under ammonium and glucose starvation conditions. Several lines of
      evidence indicated that the loss of viability of P(i)-starved cells resulted
      primarily from the catabolism of glucose into organic acids through pyruvate
      oxidase (PoxB) and pyruvate-formate lyase (PflB) under aerobic and anaerobic
      conditions, respectively. Weak organic acids that are excreted into the medium
      can reenter the cell and dissociate into protons and anions, thereby triggering
      cell death. However, P(i)-starved cells were efficiently protected by the
      activity of the inducible GadABC glutamate-dependent acid resistance system.
      Glutamate decarboxylation consumes one proton, which contributes to the internal
      pH homeostasis, and removes one intracellular negative charge, which might
      compensate for the accumulated weak acid anions. Unexpectedly, the tolerance of
      P(i)-starved cells to fermentation acids was markedly increased as a result of
      the activity of the inducible CadBA lysine-dependent acid resistance system that
      consumes one proton and produces the diamine cadaverine. CadA plays a key role in
      the defense of Salmonella at pH 3 but was thought to be ineffective in
      Escherichia coli since the protection of E. coli challenged at pH 2.5 by lysine
      is much weaker than the protection by glutamate. CadA activity was favored in
      P(i)-starved cells probably because weak organic acids slowly reenter cells
      fermenting glucose. Since the environmental conditions that trigger the death of
      P(i)-starved cells are strikingly similar to the conditions that are thought to
      prevail in the human colon (i.e., a combination of low levels of P(i) and oxygen
      and high levels of carbohydrates, inducing the microbiota to excrete high levels
      of organic acids), it is tempting to speculate that E. coli can survive in the
      gut because of the activity of the GadABC and CadBA glutamate- and lysine
      dependent acid resistance systems.

PMID- 17209033
TI  - Cytological analysis of the mother cell death process during sporulation in
      Bacillus subtilis.
AB  - We have identified the following events during the late stage in the mother cell
      in Bacillus subtilis: spore detachment from the polar site of the mother cell,
      membrane rupture, cell wall collapse, and release of the free spore. The membrane
      rupture was followed by mother cell lysis. Moreover, we found that NucB, an
      extracellular nuclease, is involved in DNA degradation after mother cell lysis.

PMID- 17209034
TI  - Porins are required for uptake of phosphates by Mycobacterium smegmatis.
AB  - Phosphorus is an essential nutrient, but how phosphates cross the mycobacterial
      cell wall is unknown. Phosphatase activity in whole cells of Mycobacterium
      smegmatis was significantly lower than that in lysed cells, indicating that
      access to the substrate was restricted. The loss of the outer membrane (OM) porin
      MspA also reduced the phosphatase activity in whole cells compared to that in
      lysed cells. A similar result was obtained for M. smegmatis that overexpressed
      endogenous alkaline phosphatase, indicating that PhoA is not a surface protein,
      contrary to a previous report. The uptake of phosphate by a mutant lacking the
      porins MspA and MspC was twofold lower than that by wild-type M. smegmatis.
      Strikingly, the loss of these porins resulted in a severe growth defect of M.
      smegmatis on low-phosphate plates. We concluded that the OM of M. smegmatis
      represents a permeability barrier for phosphates and that Msp porins are the only
      OM channels for the diffusion of phosphate in M. smegmatis. However, phosphate
      diffusion through Msp pores is rather inefficient as shown by the 10-fold lower
      permeability of M. smegmatis for phosphate compared to that for glucose. This is
      likely due to the negative charges in the constriction zone of Msp porins. The
      phosphatase activity in whole cells of Mycobacterium bovis BCG was significantly
      less than that in lysed cells, indicating a similar uptake pathway for phosphates
      in slow-growing mycobacteria. However, porins that could mediate the diffusion of
      phosphates across the OM of M. bovis BCG and Mycobacterium tuberculosis are
      unknown.

PMID- 17209035
TI  - The AppA and PpsR proteins from Rhodobacter sphaeroides can establish a redox
      dependent signal chain but fail to transmit blue-light signals in other bacteria.
AB  - The AppA protein of Rhodobacter sphaeroides has the unique ability to sense and
      transmit redox and light signals. In response to decreasing oxygen tension, AppA
      antagonizes the transcriptional regulator PpsR, which represses the expression of
      photosynthesis genes, including the puc operon. This mechanism, which is based on
      direct protein-protein interaction, is prevented by blue-light absorption of the
      BLUF domain located in the N-terminal part of AppA. In order to test whether AppA
      and PpsR are sufficient to transmit redox and light signals, we expressed these
      proteins in three different bacterial species and monitored oxygen- and blue
      light-dependent puc expression either directly or by using a luciferase-based
      reporter construct. The AppA/PpsR system could mediate redox-dependent gene
      expression in the alphaproteobacteria Rhodobacter capsulatus and Paracoccus
      denitrificans but not in the gammaproteobacterium Escherichia coli. Analysis of a
      prrA mutant strain of R. sphaeroides strongly suggests that light-dependent gene
      expression requires a balanced interplay of the AppA/PpsR system with the PrrA
      response regulator. Therefore, the AppA/PpsR system was unable to establish light
      signaling in other bacteria. Based on our data, we present a model for the
      interdependence of AppA/PpsR signaling and the PrrA transcriptional activator.

PMID- 17209036
TI  - Binding mode of the first aminoacyl-tRNA in translation initiation mediated by
      Plautia stali intestine virus internal ribosome entry site.
AB  - Eukaryotic ribosomes directly bind to the intergenic region-internal ribosome
      entry site (IGR-IRES) of Plautia stali intestine virus (PSIV) and initiate
      translation without either initiation factors or initiator Met-tRNA. We have
      investigated the mode of binding of the first aminoacyl-tRNA in translation
      initiation mediated by the IGR-IRES. Binding ability of aminoacyl-tRNA to the
      first codon within the IGR-IRES/80 S ribosome complex was very low in the
      presence of eukaryotic elongation factor 1A (eEF1A) alone but markedly enhanced
      by the translocase eEF2. Moreover, eEF2-dependent GTPase activity of the IRES/80
      S ribosome complex was 3-fold higher than that of the free 80 S ribosome. This
      activation was suppressed by addition of the antibiotics pactamycin and
      hygromycin B, which are inhibitors of translocation. The results suggest that
      translocation by the action of eEF2 is essential for stable tRNA binding to the
      first codon of the PSIV-IRES in the ribosome. Chemical probing analysis showed
      that IRES binding causes a conformational change in helix 18 of 18 S rRNA at the
      A site such that IRES destabilizes the conserved pseudoknot within the helix.
      This conformational change caused by the PSIV-IRES may be responsible for the
      activation of eEF2 action and stimulation of the first tRNA binding to the P site
      without initiation factors.

PMID- 17209037
TI  - Transforming growth factor (TGF)-beta1 stimulates pulmonary fibrosis and
      inflammation via a Bax-dependent, bid-activated pathway that involves matrix
      metalloproteinase-12.
AB  - Fibrosis, apoptosis, and the exaggerated production of transforming growth factor
      (TGF)-beta(1) are juxtaposed in a variety of pulmonary diseases including the
      interstitial lung diseases and asthma. In these disorders, the relationships
      between these responses are not well defined. In addition, the apoptosis pathways
      that contribute to these responses and the mechanism(s) of their contribution
      have not been described. We hypothesized that BH3 domain-only protein-induced
      apoptosis plays an important role in the pathogenesis of TGF-beta(1)-induced
      pulmonary responses. To test this hypothesis, we characterized the effects of
      transgenic TGF-beta(1) in mice with wild type (WT) and null Bax loci. To
      investigate the mechanisms of Bax activation and its effector functions, we also
      compared the effects of TGF-beta(1) in mice with WT and null Bid and matrix
      metalloproteinase (MMP)-12 loci, respectively. These studies demonstrate that TGF
      beta(1) is a potent stimulator of Bax, Bid, and MMP-12. The studies also
      demonstrate that Bax and Bid play key roles in the pathogenesis of TGF-beta(1)
      induced inflammation, fibrosis, and apoptosis; that TGF-beta(1) stimulates MMP
      12, TIMP-1, and cathepsins and inhibits MMP-9 and p21 via Bax- and Bid-dependent
      mechanisms; and that TGF-beta(1)-stimulated pulmonary fibrosis is ameliorated in
      MMP-12-deficient animals. Finally, they demonstrate that Bax, Bid, and MMP-12
      play similar roles in bleomycin-induced fibrosis, thereby highlighting the
      importance of this Bid-activated, Bax-mediated pathway and downstream MMP-12 in a
      variety of fibrogenic settings.

PMID- 17209038
TI  - Repression of p53-mediated transcription by adenovirus E1B 55-kDa does not
      require corepressor mSin3A and histone deacetylases.
AB  - The Ad E1B 55-kDa protein (E1B) is a potent transcriptional repressor. In vitro
      biochemical studies revealed that direct p53-E1B interaction is essential for E1B
      to block p53-activated transcription and a corepressor may be involved. To
      understand how E1B represses p53-mediated transcription in vivo, we expressed E1B
      in several tumor cell lines that express wild type p53. Here we show that E1B
      strongly suppresses the expression of p53 target genes such as p21 and Puma-alpha
      in normal growth conditions or after cells were treated with p53-activating
      chemotherapeutic agents, suggesting that E1B-mediated gene repression is dominant
      and cannot be reversed via p53 activation. Interestingly, we found that E1B binds
      to corepressor mSin3A. Mutagenesis analysis indicated that the sequence motif
      "LHLLA" near the NH(2) terminus of E1B is responsible for mSin3A binding, and
      this motif is conserved among E1B proteins from different Ad serotypes. The
      conserved paired amphipathic helix domain 1 of mSin3A is critical for mSin3A-E1B
      interaction. Surprisingly, E1B mutants that cannot bind to mSin3A can still
      repress p53 target genes, indicating that it is not the corepressor required for
      E1B-mediated gene repression. In support of this notion, repression of p53 target
      genes by E1B is insensitive to HDAC inhibitor trichostatin A. We further show
      that both the NH(2)- and COOH-terminal domains of E1B are required for the
      repression function. Therefore, E1B employs a unique repression mechanism to
      block p53-mediated transcription.

PMID- 17209039
TI  - Identification of mitochondrial complex I assembly intermediates by tracing
      tagged NDUFS3 demonstrates the entry point of mitochondrial subunits.
AB  - Biogenesis of human mitochondrial complex I (CI) requires the coordinated
      assembly of 45 subunits derived from both the mitochondrial and nuclear genome.
      The presence of CI subcomplexes in CI-deficient cells suggests that assembly
      occurs in distinct steps. However, discriminating between products of assembly or
      instability is problematic. Using an inducible NDUFS3-green fluorescent protein
      (GFP) expression system in HEK293 cells, we here provide direct evidence for the
      stepwise assembly of CI. Upon induction, six distinct NDUFS3-GFP-containing
      subcomplexes gradually appeared on a blue native Western blot also observed in
      wild type HEK293 mitochondria. Their stability was demonstrated by differential
      solubilization and heat incubation, which additionally allowed their distinction
      from specific products of CI instability and breakdown. Inhibition of
      mitochondrial translation under conditions of steady state labeling resulted in
      an accumulation of two of the NDUFS3-GFP-containing subcomplexes (100 and 150
      kDa) and concomitant disappearance of the fully assembled complex. Lifting
      inhibition reversed this effect, demonstrating that these two subcomplexes are
      true assembly intermediates. Composition analysis showed that this event was
      accompanied by the incorporation of at least one mitochondrial DNA-encoded
      subunit, thereby revealing the first entry point of these subunits.

PMID- 17209041
TI  - Mitogen-activated protein kinase-dependent activation of the Na+/H+ exchanger is
      mediated through phosphorylation of amino acids Ser770 and Ser771.
AB  - We investigated regulation of the type 1 isoform of the Na(+)/H(+) exchanger by
      phosphorylation. Four specific groups of serine and threonine residues in the
      regulatory carboxyl-terminal tail were mutated to alanine residues: group 1,
      S693A; group 2, T718A and S723A/S726A/S729A; group 3, S766A/S770A/S771A; and
      group 4, T779A and S785A. The proteins were expressed in Na(+)/H(+) exchanger
      deficient cells, and the activity was characterized. All of the mutants had
      proper expression, localization, and normal basal activity relative to wild type
      NHE1. Sustained intracellular acidosis was used to activate NHE1 via an ERK
      dependent pathway that could be blocked with the MEK inhibitor U0126.
      Immunoprecipitation of (32)P-labeled Na(+)/H(+) exchanger from intact cells
      showed that sustained intracellular acidosis increased Na(+)/H(+) exchanger
      phosphorylation in vivo. This was blocked by U0126. The Na(+)/H(+) exchanger
      activity of mutants 1 and 2 was stimulated similar to wild type Na(+)/H(+)
      exchanger. Mutant 4 showed a partially reduced level of activation. However,
      mutant 3 was not stimulated by sustained intracellular acidosis, and loss of
      stimulation of activity correlated to a loss of sustained acidosis-mediated
      phosphorylation in vivo. Mutation of the individual amino acids within mutant 3,
      Ser(766), Ser(770), and Ser(771), showed that Ser(770) and Ser(771) are
      responsible for mediating increases in NHE1 activity through sustained acidosis.
      Both intact Ser(770) and Ser(771) were required for sustained acidosis-mediated
      activation of NHE1. Our results suggest that amino acids Ser(770) and Ser(771)
      mediate ERK-dependent activation of the Na(+)/H(+) exchanger in vivo.

PMID- 17209040
TI  - A conserved cysteine residue of Pichia pastoris Pex20p is essential for its
      recycling from the peroxisome to the cytosol.
AB  - We identified a cysteine residue, conserved near the N terminus of Pex5p- and
      Pex20p-like proteins, that is essential for the cytosolic relocation of
      peroxisomal Pex20p. Surprisingly, this residue is not completely essential for
      the function of the protein; its point mutation into a serine in Pex20p(C8S)
      causes the accumulation of the protein at the peroxisome membrane, but this is
      quickly followed by its subsequent degradation by an ubiquitin-dependent quality
      control pathway called RADAR (receptor accumulation and degradation in the
      absence of recycling). This degradative pathway allows partial growth of the
      Pex20p(C8S) mutant on peroxisome-requiring medium. Mutation of cysteine 8 (C8S)
      and lysine 19 (K19R), the target residue of the RADAR pathway within Pex20p,
      leads to a stable but non-functional protein because it fails to recycle to the
      cytosol. This suggests a role for Cys-8 in Pex20p recycling and that constitutive
      degradation of peroxisomal receptors can be a partially functional alternative to
      receptor recycling. In addition, expression of this mutant protein in wild-type
      cells confers a dominant-negative, oleate-specific growth defect, which is a
      useful tool for a better understanding of peroxisomal receptor recycling.

PMID- 17209042
TI  - Biochemical and functional analyses of the human Toll-like receptor 3 ectodomain.
AB  - The structure of the human Toll-like receptor 3 (TLR3) ectodomain (ECD) was
      recently solved by x-ray crystallography, leading to a number of models
      concerning TLR3 function (Choe, J., Kelker, M. S., and Wilson, I. A. (2005)
      Science 309, 581-585; Bell, J. K., Botos, I., Hall, P. R., Askins, J., Shiloach,
      J., Segal, D. M., and Davies, D. R. (2005) Proc. Natl. Acad. Sci. U. S. A. 102,
      10976-10980) The structure revealed four pairs of cysteines that are putatively
      involved in disulfide bond formation, several residues that are predicted to be
      involved in dimerization between ECD subunits, and surfaces that could bind to
      poly(I:C). In addition, there are two loops that protrude from the central
      solenoid structure of the protein. We examined the recombinant TLR3 ECD for
      disulfide bond formation, poly(I:C) binding, and protein-protein interaction. We
      also made over 80 mutations in the residues that could affect these features in
      the full-length TLR3 and examined their effects in TLR3-mediated NF-kappaB
      activation. A number of mutations that affected TLR3 activity also affected the
      ability to act as dominant negative inhibitors of wild type TLR3. Loss of
      putative RNA binding did not necessarily affect dominant negative activity. All
      of the results support a model where a dimer of TLR3 is the form that binds RNA
      and activates signal transduction.

PMID- 17209043
TI  - Coregulated ataxia telangiectasia-mutated and casein kinase sites modulate cAMP
      response element-binding protein-coactivator interactions in response to DNA
      damage.
AB  - The cyclic AMP-response element-binding protein (CREB) is a bZIP family
      transcription factor implicated as an oncoprotein and neuron survival factor.
      CREB is activated in response to cellular stimuli, including cAMP and Ca(2+), via
      phosphorylation of Ser-133, which promotes interaction between the kinase
      inducible domain (KID) of CREB and the KID-interacting domain of CREB-binding
      protein (CBP). We previously demonstrated that the interaction between CREB and
      CBP is inhibited by DNA-damaging stimuli through a mechanism whereby CREB is
      phosphorylated by the ataxia telangiectasia-mutated (ATM) protein kinase. We now
      show that the ATM phosphorylation sites in CREB are functionally intertwined with
      a cluster of coregulated casein kinase (CK) sites. We demonstrate that DNA damage
      induced phosphorylation of CREB occurs in three steps. The initial event in the
      CREB phosphorylation cascade is the phosphorylation of Ser-111, which is carried
      out by CK1 and CK2 under basal conditions and by ATM in response to ionizing
      radiation. The phosphorylation of Ser-111 triggers the CK2-dependent
      phosphorylation of Ser-108 and the CK1-dependent phosphorylation of Ser-114 and
      Ser-117. The phosphorylation of Ser-114 and Ser-117 by CK1 then renders CREB
      permissive for ATM-dependent phosphorylation on Ser-121. Mutation of Ser-121
      alone abrogates ionizing radiation-dependent repression of CREB-CBP complexes,
      which can be recapitulated using a CK1 inhibitor. Our findings outline a complex
      mechanism of CREB phosphorylation in which coregulated ATM and CK sites control
      CREB transactivation potential by modulating its CBP-binding affinity. The
      coregulated ATM and CK sites identified in CREB may constitute a signaling motif
      that is common to other DNA damage-regulated substrates.

PMID- 17209044
TI  - FXYD6 is a novel regulator of Na,K-ATPase expressed in the inner ear.
AB  - The exquisite sensitivity of the cochlea, which mediates the transduction of
      sound waves into nerve impulses, depends on the endolymph ionic composition and
      the endocochlear potential. A key protein in the maintenance of the
      electrochemical composition of the endolymph is the Na,K-ATPase. In this study,
      we have looked for the presence in the rat inner ear of members of the FXYD
      protein family, recently identified as tissue-specific modulators of Na,K-ATPase.
      Only FXYD6 is detected at the protein level. FXYD6 is expressed in various
      epithelial cells bordering the endolymph space and in the auditory neurons. FXYD6
      co-localizes with Na,K-ATPase in the stria vascularis and can be co
      immunoprecipitated with Na,K-ATPase. After expression in Xenopus oocytes, FXYD6
      associates with Na,K-ATPase alpha1-beta1 and alpha1-beta2 isozymes, which are
      preferentially expressed in different regions of the inner ear and also with
      gastric and non-gastric H,K-ATPases. The apparent K(+) and Na(+) affinities of
      alpha1-beta1 and alpha1-beta2 isozymes are different. Association of FXYD6 with
      Na,K-ATPase alpha1-beta1 isozymes slightly decreases their apparent K(+) affinity
      and significantly decreases their apparent Na(+) affinity. On the other hand,
      association with alpha1-beta2 isozymes increases their apparent K(+) and Na(+)
      affinity. The effects of FXYD6 on the apparent Na(+) affinity of Na,K-ATPase and
      the voltage dependence of its K(+) effect are distinct from other FXYD proteins.
      In conclusion, this study defines the last FXYD protein of unknown function as a
      modulator of Na,K-ATPase. Among FXYD protein, FXYD6 is unique in its expression
      in the inner ear, suggesting a role in endolymph composition.

PMID- 17209045
TI  - Ras/ERK1/2-mediated STAT3 Ser727 phosphorylation by familial medullary thyroid
      carcinoma-associated RET mutants induces full activation of STAT3 and is required
      for c-fos promoter activation, cell mitogenicity, and transformation.
AB  - The precise role of STAT3 Ser(727) phosphorylation in RET-mediated cell
      transformation and oncogenesis is not well understood. In this study, we have
      shown that familial medullary thyroid carcinoma (FMTC) mutants RET(Y791F) and
      RET(S891A) induced, in addition to Tyr(705) phosphorylation, constitutive STAT3
      Ser(727) phosphorylation. Using inhibitors and dominant negative constructs, we
      have demonstrated that RET(Y791F) and RET(S891A) induce STAT3 Ser(727)
      phosphorylation via a canonical Ras/ERK1/2 pathway and that integration of the
      Ras/ERK1/2/ELK-1 and STAT3 pathways was required for up-regulation of the c-fos
      promoter by FMTC-RET. Moreover, inhibition of ERK1/2 had a more severe effect on
      cell proliferation and cell phenotype in HEK293 cells expressing RET(S891A)
      compared with control and RET(WT)-transfected cells. The transforming activity of
      RET(Y791F) and RET(S891A) in NIH-3T3 cells was also inhibited by U0126,
      indicating a role of the ERK1/2 pathway in RET-mediated transformation. To
      investigate the biological significance of Ras/ERK1/2-induced STAT3 Ser(727)
      phosphorylation for cell proliferation and transformation, N-Ras-transformed NIH
      3T3 cells were employed. These cells displayed elevated levels of activated
      ERK1/2 and Ser(727)-phosphorylated STAT3, which were inhibited by treatment with
      U0126. Importantly, overexpression of STAT3, in which the Ser(727) was mutated
      into Ala (STAT3(S727A)), rescued the transformed phenotype of N-Ras-transformed
      cells. Immunohistochemistry in tumor samples from FMTC patients showed strong
      nuclear staining of phosphorylated ERK1/2 and Ser(727) STAT3. These data show
      that FMTC-RET mutants activate a Ras/ERK1/2/STAT3 Ser(727) pathway, which plays
      an important role in cell mitogenicity and transformation.

PMID- 17209046
TI  - Two populations of p27 use differential kinetics to phosphorylate Ser-10 and Thr
      187 via phosphatidylinositol 3-Kinase in response to fibroblast growth factor-2
      stimulation.
AB  - The cyclin-dependent kinase inhibitor p27 regulates cell cycle progression. We
      investigated whether FGF-2 uses PI 3-kinase to facilitate phosphorylation of p27
      on serine 10 (Ser-10) and threonine 187 (Thr-187) and whether the two
      phosphorylation sites were differentially regulated. FGF-2 stimulation
      dramatically increased p27 phosphorylation at Ser-10 and Thr-187 using
      differential kinetics, and the FGF-2-induced p27 phosphorylation was completely
      blocked at both sites by LY294002. We determined the physical and biochemical
      interaction of p27 with the Cdk2-cyclin E complex in response to FGF-2
      stimulation. Maximal p27 binding to Cdk2-cyclin E occurred at 12 h; the maximal
      level of p27 phosphorylation at Thr-187 in the ternary complex was observed at 16
      h; ubiquitination of the Thr-187-phosphorylated p27 (pp27Thr-187) was observed
      starting at 12 h and continuing up to 24 h. However, maximum p27 phosphorylation
      at Ser-10 occurred in the nucleus 6 h after FGF-2 stimulation; maximal export of
      Ser-10-phosphorylated p27 (pp27Ser-10) occurred 8 h after FGF-2 treatment, and
      pp27Ser-10 was simultaneously ubiquitinated. We further investigated which of the
      two phosphorylated p27 was involved in G(1)/S progression. LY294002 blocked 64%
      of the cell proliferation stimulated by FGF-2. Use of leptomycin B to block
      nuclear export of pp27Ser-10 greatly decreased the FGF-2-stimulated cell
      proliferation (44%), suggesting that phosphorylation of p27 at Ser-10 is the
      major mechanism for G(1)/S transition. Our results suggest that differential
      kinetics are observed in p27 phosphorylation at Ser-10 and Thr-187 and that
      pp27Thr-187 and pp27Ser-10 may represent two populations of p27 observed in the
      G(1) phase of the cell cycle.

PMID- 17209047
TI  - Regulation of the gating of BKCa channel by lipid bilayer thickness.
AB  - Transmembrane segments of ion channels tend to match the hydrophobic thickness of
      lipid bilayers to minimize mismatch energy and to maintain their proper
      organization and function. To probe how ion channels respond to mismatch with
      lipid bilayers of different thicknesses, we examined the single channel
      activities of BK(Ca) (hSlo alpha-subunit) channels in planar bilayers of binary
      mixtures of DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) with
      phosphatidylcholines (PCs) of varying chain lengths, including PC 14:1, PC 18:1,
      PC 22:1, PC 24:1, and with porcine brain sphingomyelin. Bilayer thickness and
      structure was measured with small angle x-ray diffraction and atomic force
      microscopy. The open probability (P(o)) of the BK(Ca) channel was finely tuned by
      bilayer thickness, first decreasing with increases in bilayer thickness from PC
      14:1 to PC 22:1 and then increasing from PC 22:1 to PC 24:1 and to porcine brain
      sphingomyelin. Single channel kinetic analyses revealed that the mean open time
      of the channel increased monotonically with bilayer thickness and, therefore,
      could not account for the biphasic changes in P(o). The mean closed time
      increased with bilayer thickness from PC 14:1 up to PC 22:1 and then decreased
      with further increases in bilayer thickness to PC 24:1 and sphingomyelin,
      correlating with changes in P(o). This is consistent with the proposition that
      bilayer thickness affects channel activity mainly through altering the stability
      of the closed state. We suggest a simple mechanical model that combines forces of
      lateral stress within the lipid bilayer with local hydrophobic mismatch between
      lipids and the protein to account for the biphasic modulation of BK(Ca) gating.

PMID- 17209048
TI  - Human DNA replication-related element binding factor (hDREF) self-association via
      hATC domain is necessary for its nuclear accumulation and DNA binding.
AB  - We previously demonstrated that hDREF, a human homologue of Drosophila DNA
      replication-related element binding factor (dDREF), is a DNA-binding protein
      predominantly distributed with granular structures in the nucleus. Here,
      glutathione S-transferase pulldown and chemical cross-linking assays showed that
      the carboxyl-terminal hATC domain of hDREF, highly conserved among hAT
      transposase family members, possesses self-association activity.
      Immunoprecipitation analyses demonstrated that hDREF self-associates in vivo,
      dependent on hATC domain. Moreover, analyses using a series of hDREF mutants
      carrying amino acid substitutions in the hATC domain revealed that conserved
      hydrophobic amino acids are essential for self-association. Immunofluorescence
      studies further showed that all hDREF mutants lacking self-association activity
      failed to accumulate in the nucleus. Self-association-defective hDREF mutants
      also lost association with endogenous importin beta1. Moreover, electrophoretic
      gel-mobility shift assays revealed that the mutations completely abolished the
      DNA binding activity of hDREF. These results suggest that self-association of
      hDREF via the hATC domain is necessary for its nuclear accumulation and DNA
      binding. We also found that ZBED4/KIAA0637, another member of the human hAT
      family, also self-associates, again dependent on the hATC domain, with deletion
      resulting in loss of efficient nuclear accumulation. Thus, hATC domains of human
      hAT family members appear to have conserved functions in self-association that
      are required for nuclear accumulation.

PMID- 17209049
TI  - AKT and CDK5/p35 mediate brain-derived neurotrophic factor induction of DARPP-32
      in medium size spiny neurons in vitro.
AB  - Mature striatal medium size spiny neurons express the dopamine and cyclic AMP
      regulated phosphoprotein, 32 kDa (DARPP-32), but little is known about the
      mechanisms regulating its levels or the specification of fully differentiated
      neuronal subtypes. Cell extrinsic molecules that increase DARPP-32 mRNA and/or
      protein levels include brain-derived neurotrophic factor (BDNF), retinoic acid,
      and estrogen. DARPP-32 induction by BDNF in vitro requires phosphatidylinositide
      3-kinase (PI3K), but inhibition of phosphorylation of protein kinase B/Akt does
      not entirely abolish expression of DARPP-32. Moreover, the requirement for Akt
      has not been established. Using pharmacologic inhibitors of PI3K, Akt, and cyclin
      dependent kinase 5 (cdk5) and constitutively active and dominant negative PI3K,
      Akt, cdk5, and p35 viruses in cultured striatal neurons, we measured BDNF-induced
      levels of DARPP-32 protein and/or mRNA. We demonstrated that both the
      PI3K/Akt/mammalian target of rapamycin and the cdk5/p35 signal transduction
      pathways contribute to the induction of DARPP-32 protein levels by BDNF and that
      the effects are on both the transcriptional and translational levels. It also
      appears that PI3K is upstream of cdk5/p35, and its activation can lead to an
      increase in p35 protein levels. These data support the presence of multiple
      signal transduction pathways mediating expression of DARPP-32 in vitro, including
      a novel, important pathway via by which PI3K regulates the contribution of
      cdk5/p35.

PMID- 17209050
TI  - Generation of inhibitory NFkappaB complexes and phosphorylated cAMP response
      element-binding protein correlates with the anti-inflammatory activity of
      complement protein C1q in human monocytes.
AB  - The interaction of C1q with specific cells of the immune system induces
      activities, such as enhancement of phagocytosis in monocytes and stimulation of
      superoxide production in neutrophils. In contrast to some other monocyte
      activators, C1q itself does not induce pro-inflammatory cytokine production, but
      rather inhibits the lipopolysaccharide (LPS)-stimulated induction of certain pro
      inflammatory cytokines and induces expression of interleukin-10. To investigate
      the molecular mechanism by which C1q exerts this effect on gene expression, the
      influence of C1q on the activation of transcription factors of the NFkappaB
      family and cAMP response element-binding protein (CREB) was assessed. C1q
      treatment increased kappaB binding activity in freshly isolated human monocytes
      in a time-dependent fashion as assessed by electrophoretic mobility shift assays.
      In antibody supershift experiments, anti-p50 antibody supershifted the C1q
      induced NFkappaB complex, whereas anti-p65 antibody had little effect, suggesting
      that C1q induced the translocation of NFkappaB p50p50 homodimers. This is in
      contrast to the dominant induction of p65 containing complexes in parallel
      monocyte cultures stimulated with LPS. C1q treatment also induced cAMP response
      element (CRE)-binding activity as demonstrated by electrophoretic mobility shift
      assay, increased phosphorylation of CREB, and induction of CRE driven gene
      expression. In contrast, CREB activation was not detected in LPS-treated
      monocytes. These results suggest that C1q may modulate the cytokine profile
      expressed in response to inflammatory stimuli (e.g. LPS), by triggering
      inhibitory and/or competing signals. Because C1q and other defense collagens have
      been shown to enhance clearance of apoptotic cells, this regulatory pathway may
      be beneficial in avoiding autoimmunity and/or resolving inflammation.

PMID- 17209051
TI  - Human SSRP1 has Spt16-dependent and -independent roles in gene transcription.
AB  - The facilitating chromatin transcription (FACT) complex, a heterodimer of SSRP1
      and Spt16, has been shown to regulate transcription elongation through a
      chromatin template in vitro and on specific genes in cells. However, its global
      role in transcription regulation in human cells remains largely elusive. We
      conducted spotted microarray analyses using arrays harboring 8308 human genes to
      assess the gene expression profile after knocking down SSRP1 or Spt16 levels in
      human non-small cell lung carcinoma (H1299) cells. Although the changes of these
      transcripts were surprisingly subtle, there were approximately 170 genes whose
      transcript levels were either reduced or induced >1.5-fold. Approximately 106
      genes with >1.2-fold change at the level of transcripts were the common targets
      of both SSRP1 and Spt16 ( approximately 1.3%). A subset of genes was regulated by
      SSRP1 independent of Spt16. Further analyses of some of these genes not only
      verified this observation but also identified the serum-responsive gene, egr1, as
      a novel target for both SSRP1 and Spt16. We further showed that SSRP1 and Spt16
      are important for the progression of elongation RNA pol II on the egr1 gene.
      These results suggest that SSRP1 has Spt16-dependent and -independent roles in
      regulating gene transcription in human cells.

PMID- 17209053
TI  - Vitamin A potentiates CpG-mediated memory B-cell proliferation and
      differentiation: involvement of early activation of p38MAPK.
AB  - Foreign CpG-DNA from viruses and bacteria can activate memory B cells through
      binding to toll-like receptor 9, and this pathway has been hypothesized to be
      involved in the continuous activation of memory B cells ensuring life-long
      humoral immunity. In this study, we demonstrate that retinoic acid (RA) is a
      potent coactivator of this pathway in human B cells. RA enhanced the CpG-mediated
      proliferation of CD27(+) memory B cells, and the proliferative response was
      accompanied by increased immunoglobulin (Ig) secretion indicative of plasma-cell
      formation. The RA-induced proliferation was preceded by enhanced expression of
      cyclin D3, and both the expression of cyclin D3 and the induced Ig secretion were
      found to be dependent on IL-10. Of importance, RA increased the CpG-induced
      phosphorylation of ERK1/2, p38MAPK, and IkappaB as early as 30 minutes after
      stimulation. By using specific inhibitors, all the RA-mediated events, including
      proliferation, cyclin D3 expression, IL-10 secretion, and Ig secretion, were
      shown to be dependent on p38MAPK. Hence, we propose that RA can strengthen
      humoral immunity by promoting CpG-mediated stimulation of CD27(+) B cells via
      activation of p38MAPK resulting in increased proliferation and differentiation to
      Ig-secreting plasma cells.

PMID- 17209052
TI  - Mapping early conformational changes in alphaIIb and beta3 during biogenesis
      reveals a potential mechanism for alphaIIbbeta3 adopting its bent conformation.
AB  - Current evidence supports a model in which the low-affinity state of the platelet
      integrin alphaIIbbeta3 results from alphaIIbbeta3 adopting a bent conformation.
      To assess alphaIIbbeta3 biogenesis and how alphaIIbbeta3 initially adopts the
      bent conformation, we mapped the conformational states occupied by alphaIIb and
      beta3 during biogenesis using conformation-specific monoclonal antibodies (mAbs).
      We found that alphaIIbbeta3 complex formation was not limited by the availability
      of either free pro-alphaIIb or free beta3, suggesting that other molecules,
      perhaps chaperones, control complex formation. Five beta3-specific, ligand
      induced binding site (LIBS) mAbs reacted with much or all free beta3 but not with
      beta3 when in complex with mature alphaIIb, suggesting that beta3 adopts its
      mature conformation only after complex formation. Conversely, 2 alphaIIb-specific
      LIBS mAbs directed against the alphaIIb Calf-2 region adjacent to the membrane
      reacted with only minor fractions of free pro-alphaIIb, raising the possibility
      that pro-alphaIIb adopts a bent conformation early in biogenesis. Our data
      suggest a working model in which pro-alphaIIb adopts a bent conformation soon
      after synthesis, and then beta3 assumes its bent conformation by virtue of its
      interaction with the bent pro-alphaIIb.

PMID- 17209054
TI  - Neurologic complications associated with intrathecal liposomal cytarabine given
      prophylactically in combination with high-dose methotrexate and cytarabine to
      patients with acute lymphocytic leukemia.
AB  - Central nervous system (CNS) prophylaxis has led to a significant improvement in
      the outcome of patients with acute lymphocytic leukemia (ALL). Liposomal
      cytarabine (Enzon Pharmaceuticals, Piscataway, NJ; Skye Pharma, San Diego, CA),
      an intrathecal (IT) preparation of cytarabine with a prolonged half-life, has
      been shown to be safe and effective in the treatment of neoplastic meningitis.
      Liposomal cytarabine was given for CNS prophylaxis to 31 patients with newly
      diagnosed ALL. All patients were treated concurrently with hyper-CVAD
      chemotherapy (fractionated cyclophosphamide, vincristine, doxorubicin, and
      dexamethasone) including high-dose methotrexate (MTX) and cytarabine on
      alternating courses. Liposomal cytarabine 50 mg was given intrathecally on days 2
      and 15 of hyper-CVAD and day 10 of high-dose MTX and cytarabine courses until
      completion of either 3, 6, or 10 IT treatments, depending on risk for CNS
      disease. Five patients (16%) experienced serious unexpected neurotoxicity,
      including seizures, papilledema, cauda equina syndrome (n = 2), and encephalitis
      after a median of 4 IT administrations of liposomal cytarabine. Toxicities
      usually manifested after the MTX and cytarabine courses. One patient died with
      progressive encephalitis. After a median follow-up of 7 months, no isolated CNS
      relapses have been observed. Liposomal cytarabine given via intrathecal route
      concomitantly with systemic chemotherapy that crosses the blood-brain barrier
      such as high-dose MTX and cytarabine can result in significant neurotoxicity.

PMID- 17209055
TI  - ABT-869, a multitargeted receptor tyrosine kinase inhibitor: inhibition of FLT3
      phosphorylation and signaling in acute myeloid leukemia.
AB  - In 15% to 30% of patients with acute myeloid leukemia (AML), aberrant
      proliferation is a consequence of a juxtamembrane mutation in the FLT3 gene (FMS
      like tyrosine kinase 3-internal tandem duplication [FLT3-ITD]), causing
      constitutive kinase activity. ABT-869 (a multitargeted receptor tyrosine kinase
      inhibitor) inhibited the phosphorylation of FLT3, STAT5, and ERK, as well as Pim
      1 expression in MV-4-11 and MOLM-13 cells (IC(50) approximately 1-10 nM)
      harboring the FLT3-ITD. ABT-869 inhibited the proliferation of these cells
      (IC(50) = 4 and 6 nM, respectively) through the induction of apoptosis (increased
      sub-G(0)/G(1) phase, caspase activation, and PARP cleavage), whereas cells
      harboring wild-type (wt)-FLT3 were less sensitive. In normal human blood spiked
      with AML cells, ABT-869 inhibited phosphorylation of FLT3 (IC(50) approximately
      100 nM), STAT5, and ERK, and decreased Pim-1 expression. In methylcellulose-based
      colony-forming assays, ABT-869 had no significant effect up to 1000 nM on normal
      hematopoietic progenitor cells, whereas in AML patient samples harboring both
      FLT3-ITD and wt-FLT3, ABT-869 inhibited colony formation (IC(50) = 100 and 1000
      nM, respectively). ABT-869 dose-dependently inhibited MV-4-11 and MOLM-13 flank
      tumor growth, prevented tumor formation, regressed established MV-4-11
      xenografts, and increased survival by 20 weeks in an MV-4-11 engraftment model.
      In tumors, ABT-869 inhibited FLT3 phosphorylation, induced apoptosis (transferase
      mediated dUTP nick-end labeling [TUNEL]) and decreased proliferation (Ki67). ABT
      869 is under clinical development for AML.

PMID- 17209056
TI  - Inhibition of HIV-1 infection by viral chemokine U83A via high-affinity CCR5
      interactions that block human chemokine-induced leukocyte chemotaxis and receptor
      internalization.
AB  - HIV-1 strains use C-C-chemokine receptor 5, CCR5, as a coreceptor for host
      transmission. Human CCR5 chemokine ligands inhibit binding and infection, whereas
      CCR5 mutations also inhibit infection by preventing surface expression, resulting
      in delayed progression to AIDS. Here, we describe a human herpesvirus 6 (HHV-6A)
      chemokine, U83A, which binds CCR5 with higher affinity than human chemokines,
      displacing their binding and leading to inhibition of chemotaxis of human
      leukocytes. Similarly, U83A inhibits infection by HIV-1 strains which use CCR5,
      but not the CXCR4, coreceptor. Unlike human CCR5 chemokine ligands which induce
      rapid CCR5 internalization mediated via clathrin, treatment with U83A prevents
      internalization. A spliced truncated U83A isoform, U83A-N, also binds CCR5 albeit
      with lower affinity, and this correlates with lower HIV-1 infection inhibition,
      whereas further truncation abolishes binding and any inhibition. Confocal
      microscopy confirms CCR5 internalization inhibition by U83A treatment, whereas
      labeled transferrin uptake shows that endocytosis via clathrin is unaltered.
      Previous results show that, although U83A-N is an antagonist, U83A is an agonist
      for CCR1, CCR4, CCR6, and CCR8 present on immune effector and antigen-presenting
      cells and here also shown for CCR5. Thus, U83A could act as a novel inhibitor of
      HIV-1 infection while also stimulating local immunity to the virus.

PMID- 17209057
TI  - Genetic abnormalities and survival in multiple myeloma: the experience of the
      Intergroupe Francophone du Myelome.
AB  - Acquired genomic aberrations have been shown to significantly impact survival in
      several hematologic malignancies. We analyzed the prognostic value of the most
      frequent chromosomal changes in a large series of patients with newly diagnosed
      symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All
      the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe
      Francophone du Myelome benefited from an interphase fluorescence in situ
      hybridization analysis performed on purified bone marrow plasma cells. They were
      systematically screened for the following genomic aberrations: del(13), t(11;14),
      t(4;14), hyperdiploidy, MYC translocations, and del(17p). Chromosomal changes
      were observed in 90% of the patients. The del(13), t(11;14), t(4;14),
      hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%,
      39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41
      months, univariate statistical analyses revealed that del(13), t(4;14),
      nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival
      and the overall survival, whereas t(11;14) and MYC translocations did not
      influence the prognosis. Multivariate analyses on 513 patients annotated for all
      the parameters showed that only t(4;14) and del(17p) retained prognostic value
      for both the event-free and overall survivals. When compared with the currently
      used International Staging System, this prognostic model compares favorably. In
      myeloma, the genomic aberrations t(4;14) and del(17p), together with beta2
      microglobulin level, are important independent predictors of survival. These
      findings have implications for the design of risk-adapted treatment strategies.

PMID- 17209058
TI  - A newly established murine immature dendritic cell line can be differentiated
      into a mature state, but exerts tolerogenic function upon maturation in the
      presence of glucocorticoid.
AB  - The phenotype and function of murine dendritic cells (DCs) are primarily studied
      using bone-marrow-derived DCs (BM-DCs), but may be hampered by the heterogeneous
      phenotype of BM-DCs due to their differential state of maturation. Here we
      characterize a newly established murine DC line (SP37A3) of myeloid origin.
      During maintainance in the presence of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) and M-CSF, SP37A3 cells resemble immature DCs characterized by
      low expression of major histocompatibility complex (MHC) II and costimulatory
      molecules and low T-cell stimulatory capacity. Upon stimulation, SP37A3 cells
      acquire a mature phenotype and activate naive T cells as potently as BM-DCs.
      Similar to BM-DCs, SP37A3 cells activated in the presence of dexamethasone
      induced regulatory T cells, which were anergic upon restimulation and suppressed
      proliferation of naive T cells. This tolerogenic state was reflected by lower
      expression levels of costimulatory molecules and proinflammatory cytokines
      compared with mature cells, as well as up-regulated expression of FcgammaRIIB and
      interleukin-1RA (IL-1RA). SP37A3 cells were responsive to dexamethasone even when
      applied at later time points during activation, suggesting functional plasticity.
      Thus, DC line SP37A3 represents a suitable model to study functions of immature
      and mature as well as tolerogenic myeloid DCs, circumventing restrictions
      associated with the use of primary DCs and BM-DCs.

PMID- 17209059
TI  - Cladribine in a weekly versus daily schedule for untreated active hairy cell
      leukemia: final report from the Polish Adult Leukemia Group (PALG) of a
      prospective, randomized, multicenter trial.
AB  - Cladribine (2-chlorodeoxyadenosine, 2-CdA) treatment-associated infections may
      shorten potentially long-term survival in hairy cell leukemia (HCL). In search of
      the optimal mode of 2-CdA administration, 132 patients with untreated HCL were
      randomized to receive either standard 5-day 2-CdA protocol or a novel schedule of
      6 weekly 2-CdA infusions suggested to be less toxic. Analysis of treatment
      response confirmed similar complete remission rates, overall response rates,
      progression-free survival, and overall survival in both 2-CdA protocols. However,
      we did not observe lower toxicity in the weekly schedule. Of special interest, no
      significant differences were found in the rate of grade 3/4 infections (18% for
      daily and 26% for weekly protocol, difference -8.2%; 95% confidence interval [CI]
      -23.2% to 6.9%; P = .28) and the rate of septic deaths (3% for daily and 2% for
      weekly protocol, difference 1.4%; 95% CI -4.3% to 7.0%; P = .64). In conclusion,
      HCL treatment with weekly 2-CdA infusions is equally effective but no safer than
      the standard 5-day 2-CdA protocol.

PMID- 17209061
TI  - X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation.
AB  - We identified a family with gray platelet syndrome (GPS) segregating as a sex
      linked trait. Affected males had a mild bleeding disorder, thrombocytopenia, and
      large agranular platelets characteristic of GPS, while obligate carrier females
      were asymptomatic but had dimorphic platelets on peripheral smear. Associated
      findings included mild erythrocyte abnormalities in affected males. Linkage
      analysis revealed a 63 cM region on the X chromosome between markers G10578 and
      DXS6797, which segregated with the platelet phenotype and included the GATA1
      gene. Sequencing of GATA1 revealed a G-to-A mutation at position 759
      corresponding to amino acid change Arg216Gln. This mutation was previously
      described as a cause of X-linked thrombocytopenia with thalassemia (XLTT) but not
      of gray platelet syndrome. Our findings suggest that XLTT is within a spectrum of
      disorders constituting the gray platelet syndrome, and we propose that GATA1 is
      an upstream regulator of the genes required for platelet alpha-granule
      biogenesis.

PMID- 17209062
TI  - Characterization of ISXax1, a novel insertion sequence restricted to Xanthomonas
      axonopodis pv. phaseoli (variants fuscans and non-fuscans) and Xanthomonas
      axonopodis pv. vesicatoria.
AB  - ISXax1 is a novel insertion sequence belonging to the IS256 and Mutator families.
      Dot blot, Southern blot, and PCR analyses revealed that ISXax1 is restricted to
      Xanthomonas axonopodis pv. phaseoli (variants fuscans and non-fuscans) and X.
      axonopodis pv. vesicatoria strains. Directed AFLP also showed that a high degree
      of polymorphism is associated with ISXax1 insertion in these strains.

PMID- 17209060
TI  - A sequence variation scan of the coagulation factor VIII (FVIII) structural gene
      and associations with plasma FVIII activity levels.
AB  - Plasma factor VIII coagulant activity (FVIII:C) level is a highly heritable
      quantitative trait that is strongly correlated with thrombosis risk.
      Polymorphisms within only 1 gene, the ABO blood-group locus, have been
      unequivocally demonstrated to contribute to the broad population variability
      observed for this trait. Because less than 2.5% of the structural FVIII gene (F8)
      has been examined previously, we resequenced all known functional regions in 222
      potentially distinct alleles from 137 unrelated nonhemophilic individuals
      representing 7 racial groups. Eighteen of the 47 variants identified, including
      17 single-nucleotide polymorphisms (SNPs), were previously unknown. As the degree
      of linkage disequilibrium across F8 was weak overall, we used measured-genotype
      association analysis to evaluate the influence of each polymorphism on the
      FVIII:C levels in 398 subjects from 21 pedigrees known as the Genetic Analysis of
      Idiopathic Thrombophilia project (GAIT). Our results suggested that 92714C>G, a
      nonsynonymous SNP encoding the B-domain substitution D1241E, was significantly
      associated with FVIII:C level. After accounting for important covariates,
      including age and ABO genotype, the association persisted with each C-allele
      additively increasing the FVIII:C level by 14.3 IU dL(-1) (P = .016).
      Nevertheless, because the alleles of 56010G>A, a SNP within the 3' splice
      junction of intron 7, are strongly associated with 92714C>G in GAIT, additional
      studies are required to determine whether D1241E is itself a functional variant.

PMID- 17209063
TI  - Reduced contamination by the Fusarium mycotoxin zearalenone in maize kernels
      through genetic modification with a detoxification gene.
AB  - Maize is subject to ear rot caused by toxigenic Aspergillus and Fusarium species,
      resulting in contamination with aflatoxins, fumonisins, trichothecenes, and
      zearalenone (ZEN). The trichothecene group and ZEN mycotoxins are produced by the
      cereal pathogen Fusarium graminearum. A transgenic detoxification system for the
      elimination of ZEN was previously developed using an egfp::zhd101 gene
      (gfzhd101), encoding an enhanced green fluorescent protein fused to a ZEN
      degrading enzyme. In this study, we produced a transgenic maize line expressing
      an intact copy of gfzhd101 and examined the feasibility of transgene-mediated
      detoxification in the kernels. ZEN-degrading activity has been detected in
      transgenic kernels during seed maturation (for a period of 6 weeks after
      pollination). The level of detoxification activity was unaltered after an
      additional storage period of 16 weeks at 6 degrees C. When the seeds were
      artificially contaminated by immersion in a ZEN solution for 48 h at 28 degrees
      C, the total amount of the mycotoxin in the transgenic seeds was uniformly
      reduced to less than 1/10 of that in the wild type. The ZEN in the transgenic
      maize kernels was also efficiently decontaminated under conditions of lower water
      activity (aw) and temperature; e.g., 16.9 microg of ZEN was removed per gram of
      seed within 48 h at an aw of 0.90 at 20 degrees C. F. graminearum infection
      assays demonstrated an absence of ZEN in the transgenic maize seeds, while the
      mycotoxin accumulated in wild-type kernels under the same conditions. Transgene
      mediated detoxification may offer simple solutions to the problems of mycotoxin
      contamination in maize.

PMID- 17209064
TI  - Strong impact on the polycyclic aromatic hydrocarbon (PAH)-degrading community of
      a PAH-polluted soil but marginal effect on PAH degradation when priming with
      bioremediated soil dominated by mycobacteria.
AB  - Bioaugmentation of soil polluted with polycyclic aromatic hydrocarbons (PAHs) is
      often disappointing because of the low survival rate and low activity of the
      introduced degrader bacteria. We therefore investigated the possibility of
      priming PAH degradation in soil by adding 2% of bioremediated soil with a high
      capacity for PAH degradation. The culturable PAH-degrading community of the
      bioremediated primer soil was dominated by Mycobacterium spp. A microcosm
      containing pristine soil artificially polluted with PAHs and primed with
      bioremediated soil showed a fast, 100- to 1,000-fold increase in numbers of
      culturable phenanthrene-, pyrene-, and fluoranthene degraders and a 160-fold
      increase in copy numbers of the mycobacterial PAH dioxygenase gene pdo1. A
      nonpolluted microcosm primed with bioremediated soil showed a high rate of
      survival of the introduced degrader community during the 112 days of incubation.
      A nonprimed control microcosm containing pristine soil artificially polluted with
      PAHs showed only small increases in the numbers of culturable PAH degraders and
      no pdo1 genes. Initial PAH degradation rates were highest in the primed
      microcosm, but later, the degradation rates were comparable in primed and
      nonprimed soil. Thus, the proliferation and persistence of the introduced, soil
      adapted degraders had only a marginal effect on PAH degradation. Given the small
      effect of priming with bioremediated soil and the likely presence of PAH
      degraders in almost all PAH-contaminated soils, it seems questionable to prime
      PAH-contaminated soil with bioremediated soil as a means of large-scale soil
      bioremediation.

PMID- 17209065
TI  - Efficient extraction of thioreodoxin from Saccharomyces cerevisiae by ethanol.
AB  - Thioredoxin, an antioxidant protein, is a promising molecule for development of
      functional foods because it protects the gastric mucosa and reduces the
      allergenicity of allergens. To establish a method for obtaining an ample amount
      of yeast thioredoxin, we found here that thioredoxin is released from
      Saccharomyces cerevisiae by treatment with 20% ethanol. We also found that
      Japanese sake contains a considerable amount of thioredoxin.

PMID- 17209066
TI  - Characterization of airborne molds, endotoxins, and glucans in homes in New
      Orleans after Hurricanes Katrina and Rita.
AB  - In August and September 2005, Hurricanes Katrina and Rita caused breeches in the
      New Orleans, LA, levee system, resulting in catastrophic flooding. The city
      remained flooded for several weeks, leading to extraordinary mold growth in
      homes. To characterize the potential risks of mold exposures, we measured
      airborne molds and markers of molds and bacteria in New Orleans area homes. In
      October 2005, we collected air samples from 5 mildly water-damaged houses, 15
      moderately to heavily water-damaged houses, and 11 outdoor locations. The air
      filters were analyzed for culturable fungi, spores, (1-->3,1-->6)-beta-D-glucans,
      and endotoxins. Culturable fungi were significantly higher in the
      moderately/heavily water-damaged houses (geometric mean=67,000 CFU/m3) than in
      the mildly water-damaged houses (geometric mean=3,700 CFU/m3) (P=0.02). The
      predominant molds found were Aspergillus niger, Penicillium spp., Trichoderma,
      and Paecilomyces. The indoor and outdoor geometric means for endotoxins were 22.3
      endotoxin units (EU)/m3 and 10.5 EU/m3, respectively, and for (1-->3,1-->6)-beta
      D-glucans were 1.7 microg/m3 and 0.9 microg/m3, respectively. In the
      moderately/heavily water-damaged houses, the geometric means were 31.3 EU/m3 for
      endotoxins and 1.8 microg/m3 for (1-->3,1-->6)-beta-D-glucans. Molds, endotoxins,
      and fungal glucans were detected in the environment after Hurricanes Katrina and
      Rita in New Orleans at concentrations that have been associated with health
      effects. The species and concentrations were different from those previously
      reported for non-water-damaged buildings in the southeastern United States.

PMID- 17209067
TI  - Identification of bacterial DNA markers for the detection of human fecal
      pollution in water.
AB  - We used genome fragment enrichment and bioinformatics to identify several
      microbial DNA sequences with high potential for use as markers in PCR assays for
      detection of human fecal contamination in water. Following competitive solution
      phase hybridization of total DNA from human and pig fecal samples, 351 plasmid
      clones were sequenced and were determined to define 289 different genomic DNA
      regions. These putative human-specific fecal bacterial DNA sequences were then
      analyzed by dot blot hybridization, which confirmed that 98% were present in the
      source human fecal microbial community and absent from the original pig fecal DNA
      extract. Comparative sequence analyses of these sequences suggested that a large
      number (43.5%) were predicted to encode bacterial secreted or surface-associated
      proteins. Deoxyoligonucleotide primers capable of annealing to a subset of 26 of
      the candidate sequences predicted to encode factors involved in interactions with
      host cells were then used in the PCR and did not amplify markers in DNA from any
      additional pig fecal specimens. These 26 PCR assays exhibited a range of
      specificity in tests with 11 other animal sources, with more than half amplifying
      markers only in specimens from dogs or cats. Four assays were more specific,
      detecting markers only in specimens from humans, including those from 18
      different human populations examined. We then demonstrated the potential utility
      of these assays by using them to detect human fecal contamination in several
      impacted watersheds.

PMID- 17209068
TI  - Changing a single amino acid in Clostridium perfringens beta-toxin affects the
      efficiency of heterologous secretion by Bacillus subtilis.
AB  - Achieving efficient heterologous protein production and secretion by Bacillus
      subtilis is an attractive prospect, although often disappointingly low yields are
      reached. The expression of detoxified Clostridium perfringens beta-toxin (beta
      toxoid) is exemplary for this. Although beta-toxin can be efficiently expressed
      and secreted by Bacillus subtilis, the genetically detoxified, and industrially
      interesting, beta-toxoid variant is difficult to obtain in high amounts. To
      optimize the expression of this putative vaccine component, we studied the
      differences in the global gene regulation responses of B. subtilis to
      overproduction of either beta-toxin or beta-toxoid by transcriptomics. A clear
      difference was the upregulation of the CssRS regulon, known to be induced upon
      secretion stress, when beta-toxoid is produced. YkoJ, a protein of unknown
      function, was also upregulated, and we show that its expression is dependent on
      cssS. We then focused on the heterologous protein itself and found that the major
      secretion bottleneck can be traced back to a single amino acid substitution
      between the beta-toxin and the beta-toxoid, which results in the rapid
      degradation of beta-toxoid following secretion across the cytoplasmic membrane.
      In contrast to beta-toxin, beta-toxoid protein is more prone to degradation
      directly after secretion, most likely due to poor folding characteristics
      introduced with point mutations. Our results show that although the host can be
      adapted in many ways, the intrinsic properties of a heterologous protein can play
      a decisive role when optimizing heterologous protein production.

PMID- 17209069
TI  - Analysis of the mechanism and regulation of lactose transport and metabolism in
      Clostridium acetobutylicum ATCC 824.
AB  - Although the acetone-butanol-ethanol fermentation of Clostridium acetobutylicum
      is currently uneconomic, the ability of the bacterium to metabolize a wide range
      of carbohydrates offers the potential for revival based on the use of cheap, low
      grade substrates. We have investigated the uptake and metabolism of lactose, the
      major sugar in industrial whey waste, by C. acetobutylicum ATCC 824. Lactose is
      taken up via a phosphoenolpyruvate-dependent phosphotransferase system (PTS)
      comprising both soluble and membrane-associated components, and the resulting
      phosphorylated derivative is hydrolyzed by a phospho-beta-galactosidase. These
      activities are induced during growth on lactose but are absent in glucose-grown
      cells. Analysis of the C. acetobutylicum genome sequence identified a gene
      system, lacRFEG, encoding a transcriptional regulator of the DeoR family, IIA and
      IICB components of a lactose PTS, and phospho-beta-galactosidase. During growth
      in medium containing both glucose and lactose, C. acetobutylicum exhibited a
      classical diauxic growth, and the lac operon was not expressed until glucose was
      exhausted from the medium. The presence upstream of lacR of a potential
      catabolite responsive element (cre) encompassing the transcriptional start site
      is indicative of the mechanism of carbon catabolite repression characteristic of
      low-GC gram-positive bacteria. A pathway for the uptake and metabolism of lactose
      by this industrially important organism is proposed.

PMID- 17209070
TI  - Validation of mixed-genome microarrays as a method for genetic discrimination.
AB  - Comparative genomic hybridizations have been used to examine genetic
      relationships among bacteria. The microarrays used in these experiments may have
      open reading frames from one or more reference strains (whole-genome
      microarrays), or they may be composed of random DNA fragments from a large number
      of strains (mixed-genome microarrays [MGMs]). In this work both experimental and
      virtual arrays are analyzed to assess the validity of genetic inferences from
      these experiments with a focus on MGMs. Empirical data are analyzed from an
      Enterococcus MGM, while a virtual MGM is constructed in silico using sequenced
      genomes (Streptococcus). On average, a small MGM is capable of correctly deriving
      phylogenetic relationships between seven species of Enterococcus with accuracies
      of 100% (n=100 probes) and 95% (n=46 probes); more probes are required for
      intraspecific differentiation. Compared to multilocus sequence methods and whole
      genome microarrays, MGMs provide additional discrimination between closely
      related strains and offer the possibility of identifying unique strain or lineage
      markers. Representational bias can have mixed effects. Microarrays composed of
      probes from a single genome can be used to derive phylogenetic relationships,
      although branch length can be exaggerated for the reference strain. We describe a
      case where disproportional representation of different strains used to construct
      an MGM can result in inaccurate phylogenetic inferences, and we illustrate an
      algorithm that is capable of correcting this type of bias. The bias correction
      algorithm automatically provides bootstrap confidence values and can provide
      multiple bias-corrected trees with high confidence values.

PMID- 17209071
TI  - Individual and combined effects of ph and lactic acid concentration on Listeria
      innocua inactivation: development of a predictive model and assessment of
      experimental variability.
AB  - In food technology, organic acids (e.g., lactic acid, acetic acid, and citric
      acid) are popular preservatives. The purpose of this study was to separate the
      individual effects of the influencing factors pH and undissociated lactic acid on
      Listeria innocua inactivation. Therefore, the inactivation process was
      investigated under controlled, initial conditions of pH (pH0) and undissociated
      lactic acid ([LaH]0). The resulting inactivation curves consisted of a (sometimes
      negligible) shoulder period followed by a descent phase. In a few cases, a
      tailing phase was observed. Depending on the conditions, the descent phase
      contained one or two log-linear parts or had a convex or concave shape. In
      addition, the inactivation process was characterized by a certain variability,
      dependent on the severity of the conditions. Furthermore, in the neighborhood of
      the growth/no growth interface sometimes contradictory observations occurred.
      Overall, the individual effects of the influencing factors pH and undissociated
      lactic acid could clearly be distinguished and were also apparent based on
      fluorescence microscopy. Appropriate model types were developed and enabled
      prediction of which conditions of pH0 and [LaH]0 are necessary to obtain a
      predetermined inactivation (number of decimal reductions) within a predetermined
      time range.

PMID- 17209072
TI  - Growth yields in bacterial denitrification and nitrate ammonification.
AB  - Denitrification and nitrate ammonification are considered the highest-energy
      yielding respiration systems in anoxic environments after oxygen has been
      consumed. The corresponding free energy changes are 7 and 35% lower than that of
      aerobic respiration, respectively. Growth yield determinations with pure cultures
      of Paracoccus denitrificans and Pseudomonas stutzeri revealed that far less
      energy is converted via ATP into cell mass than expected from the above
      calculations. Denitrification with formate or hydrogen as electron donor yielded
      about 2.4 to 3.0 g dry matter per mol formate or hydrogen and 15 to 18 g dry
      matter per mol acetate. Similar yields with acetate were obtained with
      Pseudomonas stutzeri. Wolinella succinogenes and Sulfurospirillum deleyianum,
      which reduce nitrate to ammonia, both exhibited similar yield values with formate
      or H2 plus nitrate. The results indicate that ATP synthesis in denitrification is
      far lower than expected from the free energy changes and even lower than in
      nitrate ammonification. The results are discussed against the background of our
      present understanding of electron flow in denitrification and with respect to the
      importance of denitrification and nitrate ammonification in the environment.

PMID- 17209073
TI  - Photoreactivation and dark repair in UV-treated microorganisms: effect of
      temperature.
AB  - Because of the lack of readily available information about the influence of
      temperature on microorganism reactivation processes subsequent to inactivation
      with UV radiation, a series of batch reactivation studies were performed at 5,
      10, 15, 20, 25, and 30 degrees C. A special effort was made to model the
      reactivation process to enable the effect of the temperature variable to be
      quantified. Because an earlier-proposed kinetic model (K. Kashimada, N. Kamiko,
      K. Yamamoto, and S. Ohgaki, Water Sci. Technol. 33:261-269, 1996), a first-order
      saturation type, does not adequately fit the data obtained in experiments of
      reactivation in conditions of light and darkness, a modification of that model is
      proposed. The new model, which actually coincides with the classical logistic
      equation, incorporates two kinetic parameters: the maximum survival ratio (Sm)
      and the second-order reactivation rate constant (k2). In order to interpret
      correctly the reactivation occurring in conditions of darkness, a new term for
      the decay is added to the logistic equation. The new model accurately fits the
      data obtained in reactivation experiments, permitting the interpretation of the
      kinetic parameters Sm, k2, and M (for only repair in darkness), where M is
      mortality, a zero-order decay rate constant, and their relationship with various
      environmental conditions, such as microbial type, light, and temperature. The
      parameters Sm and k2 (and M for reactivation in conditions of darkness) show
      exponential dependence on the reactivating temperature, and it is possible to
      predict their values and hence the reactivation curve from the equations proposed
      in this work.

PMID- 17209074
TI  - Expression of plant flavor genes in Lactococcus lactis.
AB  - Lactic acid bacteria, such as Lactococcus lactis, are attractive hosts for the
      production of plant-bioactive compounds because of their food grade status,
      efficient expression, and metabolic engineering tools. Two genes from strawberry
      (Fragaria x ananassa), encoding an alcohol acyltransferase (SAAT) and a
      linalool/nerolidol synthase (FaNES), were cloned in L. lactis and actively
      expressed using the nisin-induced expression system. The specific activity of
      SAAT could be improved threefold (up to 564 pmol octyl acetate h-1 mg protein-1)
      by increasing the concentration of tRNA1Arg, which is a rare tRNA molecule in L.
      lactis. Fermentation tests with GM17 medium and milk with recombinant L. lactis
      strains expressing SAAT or FaNES resulted in the production of octyl acetate (1.9
      microM) and linalool (85 nM) to levels above their odor thresholds in water. The
      results illustrate the potential of the application of L. lactis as a food grade
      expression platform for the recombinant production of proteins and bioactive
      compounds from plants.

PMID- 17209075
TI  - Quantitative assessment of the tetracycline resistance gene pool in cheese
      samples by real-time TaqMan PCR.
AB  - A TaqMan real-time PCR assay was developed to quantify the tetS gene pool present
      in retail cheeses. This protocol offers a rapid, specific, sensitive, and culture
      independent method for assessing antibiotic resistance genes in food samples rich
      in fats and proteins.

PMID- 17209076
TI  - Air-liquid interface biofilms of Bacillus cereus: formation, sporulation, and
      dispersion.
AB  - Biofilm formation by Bacillus cereus was assessed using 56 strains of B. cereus,
      including the two sequenced strains, ATCC 14579 and ATCC 10987. Biofilm
      production in microtiter plates was found to be strongly dependent on incubation
      time, temperature, and medium, as well as the strain used, with some strains
      showing biofilm formation within 24 h and subsequent dispersion within the next
      24 h. A selection of strains was used for quantitative analysis of biofilm
      formation on stainless steel coupons. Thick biofilms of B. cereus developed at
      the air-liquid interface, while the amount of biofilm formed was much lower in
      submerged systems. This suggests that B. cereus biofilms may develop particularly
      in industrial storage and piping systems that are partly filled during operation
      or where residual liquid has remained after a production cycle. Moreover,
      depending on the strain and culture conditions, spores constituted up to 90% of
      the total biofilm counts. This indicates that B. cereus biofilms can act as a
      nidus for spore formation and subsequently can release their spores into food
      production environments.

PMID- 17209078
TI  - Aftershocks of cancer chemotherapy: managing adverse effects.
AB  - Most cytotoxic chemotherapy protocols used in small animals are designed to have
      a low risk of adverse effects; however, adverse events can occasionally occur.
      Timely and appropriate management of adverse events greatly increases client
      satisfaction and the likelihood of a successful treatment outcome. This article
      presents guidelines for the management of chemotherapy-associated hematological
      and gastrointestinal disturbances, extravasation injury, and anaphylaxis.

PMID- 17209079
TI  - Effects of diazepam or lidocaine premedication on propofol induction and
      cardiovascular parameters in dogs.
AB  - The effects of diazepam or lidocaine on the propofol induction dose and certain
      cardiovascular parameters were documented in this randomized, blinded study. Dogs
      received 0.9% saline (0.1 mL/kg intravenously [i.v.]), lidocaine (2 mg/kg i.v.),
      or diazepam (0.25 mg/kg i.v.) prior to propofol i.v. until loss of jaw tone was
      achieved (up to a maximum of 8 mg/kg). Propofol was followed by 0.3 mg/kg
      atracurium i.v. Direct arterial blood pressures and heart rates were recorded
      before premedication, induction, and intubation. No statistically significant
      differences were found among the groups for cardiovascular measurements or for
      the propofol dose required for intubation.

PMID- 17209077
TI  - Localization of ruminal cellulolytic bacteria on plant fibrous materials as
      determined by fluorescence in situ hybridization and real-time PCR.
AB  - To visualize and localize specific bacteria associated with plant materials, a
      new fluorescence in situ hybridization (FISH) protocol was established. By using
      this protocol, we successfully minimized the autofluorescence of orchard grass
      hay and detected rumen bacteria attached to the hay under a fluorescence
      microscope. Real-time PCR assays were also employed to quantitatively monitor the
      representative fibrolytic species Fibrobacter succinogenes and Ruminococcus
      flavefaciens and also total bacteria attached to the hay. F. succinogenes was
      found firmly attached to not only the cut edges but also undamaged inner surfaces
      of the hay. Cells of phylogenetic group 1 of F. succinogenes were detected on
      many stem and leaf sheath fragments of the hay, even on fragments on which few
      other bacteria were seen. Cells of phylogenetic group 2 of F. succinogenes were
      often detected on hay fragments coexisting with many other bacteria. On the basis
      of 16S rRNA gene copy number analysis, the numbers of bacteria attached to the
      leaf sheaths were higher than those attached to the stems (P<0.05). In addition,
      R. flavefaciens had a greater tendency than F. succinogenes to be found on the
      leaf sheath (P<0.01) with formation of many pits. F. succinogenes, particularly
      phylogenetic group 1, is suggested to possibly play an important role in fiber
      digestion, because it is clearly detectable by FISH and is the bacterium with the
      largest population size in the less easily degradable hay stem.

PMID- 17209080
TI  - Surveillance of infections associated with intravenous catheters in dogs and cats
      in an intensive care unit.
AB  - Positive catheter-tip culture rates and risk factors associated with bacterial
      colonization of intravenous (i.v.) catheters were assessed in dogs and cats.
      Aerobic and anaerobic bacterial cultures were performed on 151 catheters, and
      24.5% were positive. Of the positive cultures, 46.0% grew Enterobacter spp. The
      type of catheter used, blood sampling through the catheter, the type of i.v.
      infusate administered, the duration the catheter was in place, the catheter
      location, complications with the catheter, and the final outcome of the animal
      were not associated with an increased risk of a positive bacterial culture from
      the catheter tip.

PMID- 17209081
TI  - Evaluation of azathioprine on lesion severity and lymphocyte blastogenesis in
      dogs with perianal fistulas.
AB  - Fourteen dogs with perianal fistulas were entered into a prospective clinical
      study to investigate the effects of long-term azathioprine on clinical outcome
      and to determine if the clinical results correlated with lymphocyte blastogenesis
      tests. Complete remission of perianal fistulas was seen in eight (57%) of 14
      dogs; partial remission occurred in one (7%) dog; and no response was detected in
      five (36%) dogs. The results of lymphocyte blastogenesis assays did not correlate
      with therapeutic response.

PMID- 17209082
TI  - Phase II clinical trial of combination chemotherapy with dexamethasone for
      lymphoma in dogs.
AB  - Dogs with histologically confirmed lymphoma were treated with a 14-week induction
      chemotherapy protocol that included dexamethasone. A phase II clinical trial was
      done using a standard two-stage design. Complete remission occurred in 21 (88%)
      dogs, with a median initial progression-free interval of 186 days. Toxicity was
      mild and self-limiting in the majority of dogs.

PMID- 17209083
TI  - Long-term outcomes in dogs with sinonasal aspergillosis treated with intranasal
      infusions of enilconazole.
AB  - Long-term outcomes (mean 38+/-17 months) were evaluated in 27 dogs with sinonasal
      aspergillosis after successful medical treatment using intranasal infusions of 1%
      or 2% enilconazole (1%, n=15; 2%, n=12). Long-term outcomes with both treatment
      protocols were good, with half of the dogs being asymptomatic throughout the
      follow-up period. The remaining dogs showed mild clinical signs compatible with
      chronic rhinitis/sinusitis. These clinical signs were interpreted as chronic
      lymphoplasmacytic rhinitis/sinusitis and episodes of bacterial rather than fungal
      infection. Three dogs had confirmed reinfection or relapse 2 to 36 months after
      clinical resolution.

PMID- 17209084
TI  - A histopathological comparison of two techniques for soft palate resection in
      normal dogs.
AB  - Eighteen dogs were used to compare histopathological findings following excision
      of the soft palate using either a bipolar sealing device or a carbon dioxide
      laser. Histopathological comparisons were done at 48 and 96 hours after soft
      palate resection. Mean depths of tissue injury at 96 hours were 3.5 and 3.33 mm
      for bipolar sealing device and carbon dioxide laser, respectively. Control of
      hemorrhage was excellent in all dogs, and none of the dogs developed signs of
      respiratory compromise after soft palate resection. Using the bipolar sealing
      device for soft palate resection was significantly faster than using the carbon
      dioxide laser, although both techniques were fast.

PMID- 17209085
TI  - Parotid duct sialolithiasis in a dog.
AB  - Computed tomography was used to evaluate a 7-year-old English bulldog with a
      history of facial swelling and to aid in the diagnosis of parotid duct
      sialolithiasis. Removal of the sialolith with repair of the duct was not possible
      because of ductal fibrosis. Histological evaluation revealed glandular atrophy
      and fibrosis with lymphoplasmacytic inflammation. The parotid duct was ulcerated
      and fibrotic, with a mixed inflammatory infiltrate. Surgical excision of the
      parotid duct and salivary gland was curative.

PMID- 17209087
TI  - Antibiotic-resistant Corynebacterium jeikeium urinary tract infection in a cat.
AB  - A 10-year-old, castrated male, domestic longhaired cat with a history of urinary
      tract disease and perineal urethrostomy was presented for evaluation of
      persistent urinary tract inflammation. Prior to referral, diphtheroid organisms
      had been cultured from a urine sample obtained by cystocentesis, and they were
      interpreted as sample contamination. Subsequent urine culture and gene sequencing
      identified Corynebacterium jeikeium, which was resistant to antibiotics and
      appeared to be the cause of the urinary tract infection.

PMID- 17209086
TI  - Unusual case of osteopenia associated with nutritional calcium and vitamin D
      deficiency in an adult dog.
AB  - A 6-year-old, spayed female rottweiler was presented for facial enlargement from
      swelling of the maxilla and mandible. The dog was fed a homemade diet deficient
      in calcium and vitamin D, suggesting that rubber jaw syndrome was a secondary
      nutritional disorder. Radiographic and tomodensitometric examinations revealed
      diffuse bone resorption in the skull. The plasma parathormone concentration was
      high, and serum 25-hydroxycholecalciferol concentration was low. Based on these
      findings, nutritional calcium and vitamin D deficiency associated with secondary
      hyperparathyroidism was diagnosed. Dietary correction resulted in clinical and
      biological improvement, with an increase in skull mineralization.

PMID- 17209088
TI  - Insulinoma in a dog with pre-existing insulin-dependent diabetes mellitus.
AB  - A 10-year-old golden retriever with a 3-year history of insulin-dependent
      diabetes mellitus was presented with recurring episodes of hypoglycemia and
      seizures. A presumptive diagnosis of an insulinoma was made based on hypoglycemia
      with concurrent endogenous hyperinsulinemia and unremarkable radiographic and
      ultrasonographic images of the chest and abdomen. A beta cell carcinoma of the
      pancreas with metastasis to the liver and a mesenteric lymph node was confirmed
      by surgery and histopathology.

PMID- 17209089
TI  - Evaluation of a laryngoscope and a rigid endoscope for the examination of the
      oral cavity of small mammals.
AB  - The oral cavities of 65 rabbits, 35 chinchillas, 38 guinea pigs, 19 degus and 13
      prairie dogs suffering from a lack of appetite, hypersalivation, moist
      dermatitis, swelling of the lower jaw or mild exophthalmos were examined with a
      paediatric laryngoscope and rigid endoscope. The laryngoscope was safe and
      satisfactory for a preliminary examination, but changes in the less accessible
      caudal parts of the cavity could not be identified precisely. A rigid endoscope
      with 30 degrees optics made it possible to examine all parts of the oral cavity
      and oropharynx, and make detailed observations of surface lesions on the premolar
      and molar teeth and the mucosal surface of the gingiva, tongue and hard palate;
      endoscopy with 70 degrees optics provided an excellent view of the occlusal tooth
      surfaces, tooth crowns, and buccal mucosa. The collection of biopsy samples, the
      removal of foreign objects and the correction of malocclusions were greatly
      simplified by the use of the endoscope owing to the clear visualisation of the
      procedures, and the risk of injury was minimised. The examinations with a
      laryngoscope were made effectively on animals that were manually restrained, but
      a thorough examination with a rigid endoscope required the animals to be
      anaesthetised.

PMID- 17209091
TI  - Causative organisms and somatic cell counts in subclinical intramammary
      infections in milking goats in the UK.
AB  - The bacterial causes of subclinical mastitis were determined in samples of milk
      taken from one half of the udders of 159 goats in three different herds. The mean
      prevalence of subclinical infection was 33 percent, with prevalences of 26
      percent, 39 percent and 42 percent in the three herds. Staphylococcus aureus was
      isolated from seven (13 percent) of the 53 infected halves, coagulase-negative
      staphylococci accounted for 47 percent, Corynebacterium species for 31 percent
      and alpha-haemolytic streptococci for 6 percent of the infected samples. The mean
      somatic cell count of the uninfected milk samples was 428,000 cells/ml, and 93
      percent of uninfected samples had counts less than 1,000,000 cells/ml; the mean
      cell count of the infected samples was 2,785,000 cells/ml.

PMID- 17209090
TI  - Vitamin A requirements of alipochromatic ('recessive-white') and coloured
      canaries (Serinus canaria) during the breeding season.
AB  - Six pairs of alipochromatic ('recessive-white') canaries (Serinus canaria) and
      six pairs of coloured canaries were kept through a complete breeding cycle while
      being fed a diet providing 12,000 iu vitamin A/kg. The eggs of three pairs (one
      recessive-white and two coloured) were all unfertilised and there were only 23
      hatchlings (14 recessive-white and nine coloured), of which 14 (10 recessive
      white and four coloured) were alive after the first moult. However, there was no
      clinical, biochemical or pathological evidence that the recessive-white canaries
      were suffering from vitamin A deficiency or that the coloured canaries were
      suffering from vitamin A toxicity, suggesting that the diet met the vitamin A
      requirements of both groups.

PMID- 17209092
TI  - Use of deep nasopharyngeal swabs as a predictive diagnostic method for natural
      respiratory infections in calves.

PMID- 17209093
TI  - Successful treatment of ocular equine microfilariasis (Setaria species) with
      ivermectin.

PMID- 17209094
TI  - DNA fingerprinting of Riemerella anatipestifer isolates from ducks.

PMID- 17209095
TI  - Vet to be suspended for 'cosmetic' tail docking.

PMID- 17209096
TI  - FMD and the contiguous cull.

PMID- 17209097
TI  - FMD and the contiguous cull.

PMID- 17209098
TI  - Equine disease surveillance, July to September 2006: *update on equine
      leptospirosis, *improving the quality of veterinary surveillance, *review of
      colic data from the University of Liverpool Equine Hospital--these are among
      matters discussed in the quarterly equine disease surveillance report for July to
      September 2006 prepared by DEFRA, the Animal Health Trust and the British Equine
      Veterinary Association.

PMID- 17209099
TI  - Use of fluoroquinolones in cats.

PMID- 17209100
TI  - High hopes and automatic escalators: a critique of some new arguments in
      bioethics.
AB  - Two protechnology arguments, the "hopeful principle" and the "automatic
      escalator", often used in bioethics, are identified and critically analysed in
      this paper. It is shown that the hopeful principle is closely related to the
      problematic precautionary principle, and the automatic escalator argument has
      close affinities to the often criticised empirical slippery slope argument. The
      hopeful principle is shown to be really hopeless as an argument, and automatic
      escalator arguments often lead nowhere when critically analysed. These arguments
      should therefore only be used with great caution.

PMID- 17209101
TI  - Should the precautionary principle guide our actions or our beliefs?
AB  - Two interpretations of the precautionary principle are considered. According to
      the normative (action-guiding) interpretation, the precautionary principle should
      be characterised in terms of what it urges doctors and other decision makers to
      do. According to the epistemic (belief-guiding) interpretation, the precautionary
      principle should be characterised in terms of what it urges us to believe. This
      paper recommends against the use of the precautionary principle as a decision
      rule in medical decision making, based on an impossibility theorem presented in
      Peterson (2005). However, the main point of the paper is an argument to the
      effect that decision theoretical problems associated with the precautionary
      principle can be overcome by paying greater attention to its epistemic dimension.
      Three epistemic principles inherent in a precautionary approach to medical risk
      analysis are characterised and defended.

PMID- 17209102
TI  - Truth telling, autonomy and the role of metaphor.
AB  - This paper examines the potential role of metaphors in helping healthcare
      professionals to communicate honestly with patients and in helping patients gain
      a richer and more nuanced understanding of what is being explained. One of the
      ways in which doctors and nurses may intentionally, or unintentionally, avoid
      telling the truth to patients is either by using metaphors that obscure the truth
      or by failing to deploy appropriately powerful and revealing metaphors in their
      discussions. This failure to tell the truth may partly account for the
      observation by clinicians that patients sometimes make decisions that, from the
      perspective of their clinician, and given all that the clinician knows, seem
      unwise. For example, patients with advanced cancer may choose to undergo further,
      aggressive, treatment despite the fact that they are likely to accrue little or
      no benefit as a result. While acknowledging that the immediate task of telling
      patients the truth can be difficult for all those concerned, I argue that the
      long-term consequences of denying patients autonomy at the end of life can be
      harmful to patients and can leave doctors and nurses distressed and confused.

PMID- 17209103
TI  - Unesco's Global Ethics Observatory.
AB  - The Global Ethics Observatory, launched by the United Nations Educational,
      Scientific, and Cultural Organization in December 2005, is a system of databases
      in the ethics of science and technology. It presents data on experts in ethics,
      on institutions (university departments and centres, commissions, councils and
      review boards, and societies and associations) and on teaching programmes in
      ethics. It has a global coverage and will be available in six major languages.
      Its aim is to facilitate the establishment of ethical infrastructures and
      international cooperation all around the world.

PMID- 17209104
TI  - The possibility of a universal declaration of biomedical ethics.
AB  - Statements on issues in biomedical ethics, purporting to represent international
      interests, have been put forth by numerous groups. Most of these groups are
      composed of thinkers in the tradition of European secularism, and do not take
      into account the values of other ethical systems. One fifth of the world's
      population is accounted for by Islam, which is a universal religion, with more
      than 1400 years of scholarship. Although many values are held in common by
      secular ethical systems and Islam, their inferences are different. The question,
      "Is it possible to derive a truly universal declaration of biomedical ethics?" is
      discussed here by examining the value and extent of personal autonomy in Western
      and Islamic biomedical ethical constructs. These constructs are then tested vis-a
      vis the issue of abortion. It is concluded that having a universal declaration of
      biomedical ethics in practice is not possible, although there are many conceptual
      similarities and agreements between secular and Islamic value systems, unless a
      radical paradigm shift occurs in segments of the world's deliberative bodies. The
      appellation "universal" should not be used on deliberative statements unless the
      ethical values of all major schools of thought are satisfied.

PMID- 17209106
TI  - Culpability and blame after pregnancy loss.
AB  - The problem of feeling guilty about a pregnancy loss is suggested to be primarily
      a moral matter and not a medical or psychological one. Two standard approaches to
      women who blame themselves for a loss are first introduced, characterised as
      either psychologistic or deterministic. Both these approaches are shown to
      underdetermine the autonomy of the mother by depending on the notion that the
      mother is not culpable for the loss if she "could not have acted otherwise". The
      inability to act otherwise is explained as not being as strong a determinant of
      culpability as it may seem at first. Instead, people's culpability for a bad turn
      of events implies strongly that they have acted for the wrong reasons, which is
      probably not true in the case of women who have experienced a loss of pregnancy.
      The practical conclusion of this paper is that women who feel a sense of guilt in
      the wake of their loss have a good reason to reject both the psychologistic and
      the deterministic approaches to their guilt-that they are justified in feeling
      upset about what has gone wrong, even responsible for the life of the child, but
      are not culpable for the unfortunate turn of events.

PMID- 17209105
TI  - Perspectives on ethics.
AB  - In his recent paper about understanding ethical issues, Boyd suggests that
      traditional approaches based on principles or people are understood better in
      terms of perspectives, especially the perspective-based approach of hermeneutics,
      which he uses for conversation rather than controversy. However, we find that
      Boyd's undefined contrast between conversation and controversy does not point to
      any improvement in communication: disputes occur during conversation and
      controversy may be conducted in gentle tones. We agree with Boyd, that being
      prepared to listen and learn are excellent attitudes, but his vague attempts to
      establish these and similar virtues in hermeneutic theory are not plausible.
      Additionally, the current controversy about the use of human embryos in stem cell
      therapy research shows Boyd missing the opportunity to illustrate how
      conversation would improve understanding.

PMID- 17209107
TI  - Crimes and misdemeanours: the case of child abandonment.
AB  - In 2002, a child was abandoned in a Burger King restaurant in Amsterdam by a
      Chinese woman, who hoped that the baby would be picked up by someone able to give
      the child a better life. She was convicted for child abandonment and imprisoned.
      Whereas some forms of child abandonment are criminalised, others are socially
      accepted and not even on the ethics agenda. This paper is an invitation to
      reflect on the inconsistency in the ways in which we prosecute, punish or try to
      correct some forms of child abandonment and yet make allowances for others.

PMID- 17209108
TI  - Responsibilities and obligations of using human research specimens transported
      across national boundaries.
AB  - Research collaboration beyond national jurisdiction is one aspect of the
      globalisation of health research. It has potential to complement researchers in
      terms of research skills, equipment and lack of adequate numbers of potential
      research subjects. Collaboration at an equal level of partnership though
      desirable, may not be practicable. Sometimes, human research specimens must be
      transported from one country to other. Where this occurs, there should be clear
      understanding between the collaborating research institutions regarding issues of
      access and control of the specimens as well as the duration of storage of
      specimens. The researchers have the duty to inform the research participants
      about specimen storage and transport across national boundaries. While obtaining
      informed consent from study subjects if specimens are to be stored beyond the
      life of the present study could be the ideal, there still remains significant
      challenges in a multi-cultural world.

PMID- 17209109
TI  - Should research ethics committees be told how to think?
AB  - Research ethics committees (RECs) are charged with providing an opinion on
      whether research proposals are ethical. These committees are overseen by a
      central office that acts for the Department of Health and hence the State. An
      advisory group has recently reported back to the Department of Health,
      recommending that it should deal with (excessive) inconsistency in the decisions
      made by different RECs. This article questions the desirability and feasibility
      of questing for consistent ethical decisions.

PMID- 17209110
TI  - Acupuncture trials and informed consent.
AB  - Participants are often not informed by investigators who conduct randomised,
      placebo-controlled acupuncture trials that they may receive a sham acupuncture
      intervention. Instead, they are told that one or more forms of acupuncture are
      being compared in the study. This deceptive disclosure practice lacks a
      compelling methodological rationale and violates the ethical requirement to
      obtain informed consent. Participants in placebo-controlled acupuncture trials
      should be provided an accurate disclosure regarding the use of sham acupuncture,
      consistent with the practice of placebo-controlled drug trials.

PMID- 17209111
TI  - Is the NHS research ethics committees system to be outsourced to a low-cost
      offshore call centre? Reflections on human research ethics after the Warner
      Report.
AB  - The recently published Report of the AHAG on the Operation of NHS Research Ethics
      Committees (the Warner Report) advocates major reforms of the NHS research ethics
      committees system. The main implications of the proposed changes and their
      probable effects on the major stakeholders are described.

PMID- 17209112
TI  - How tall is too tall? On the ethics of oestrogen treatment for tall girls.
AB  - Oestrogen treatment for girls, to prevent psychosocial problems due to extreme
      tallness, has been available for almost 50 years but uncertainty about its
      position prevails. The ethical problems of this treatment are focused on in this
      paper. After a brief overview on historical and medical aspects, ethical issues
      such as the general justification of oestrogen treatment, evaluation of its
      success and ethical concerns related to research in this subject are dealt with
      in detail.

PMID- 17209113
TI  - Ethical difficulties in clinical practice: experiences of European doctors.
AB  - BACKGROUND: Ethics support services are growing in Europe to help doctors in
      dealing with ethical difficulties. Currently, insufficient attention has been
      focused on the experiences of doctors who have faced ethical difficulties in
      these countries to provide an evidence base for the development of these
      services. METHODS: A survey instrument was adapted to explore the types of
      ethical dilemma faced by European doctors, how they ranked the difficulty of
      these dilemmas, their satisfaction with the resolution of a recent ethically
      difficult case and the types of help they would consider useful. The
      questionnaire was translated and given to general internists in Norway,
      Switzerland, Italy and the UK. RESULTS: Survey respondents (n=656, response rate
      43%) ranged in age from 28 to 82 years, and averaged 25 years in practice. Only a
      minority (17.6%) reported having access to ethics consultation in individual
      cases. The ethical difficulties most often reported as being encountered were
      uncertain or impaired decision-making capacity (94.8%), disagreement among
      caregivers (81.2%) and limitation of treatment at the end of life (79.3%). The
      frequency of most ethical difficulties varied among countries, as did the type of
      issue considered most difficult. The types of help most often identified as
      potentially useful were professional reassurance about the decision being correct
      (47.5%), someone capable of providing specific advice (41.1%), help in weighing
      outcomes (36%) and clarification of the issues (35.9%). Few of the types of help
      expected to be useful varied among countries. CONCLUSION: Cultural differences
      may indeed influence how doctors perceive ethical difficulties. The type of help
      needed, however, did not vary markedly. The general structure of ethics support
      services would not have to be radically altered to suit cultural variations among
      the surveyed countries.

PMID- 17209114
TI  - Framing, truth telling and the problem with non-directive counselling.
AB  - In this paper several reasons as to why framing issues should be of greater
      interest to both medical ethicists and healthcare professionals are suggested:
      firstly, framing can help in explaining health behaviours that can, from the
      medical perspective, appear perverse; secondly, framing provides a way of
      describing the internal structure of ethical arguments; and thirdly, an
      understanding of framing issues can help in identifying clinical practices, such
      as non-directive counselling, which may, inadvertently, be failing to meet their
      own stated ethical aims. The effect of framing on how individuals interpret
      information and how healthcare choices are influenced by framing are described.
      Next, the role of framing in ethical discourse is discussed with specific
      reference to Judith Jarvis Thomson's philosophical mind experiment about abortion
      and the violinist. Finally, the implications of this analysis are examined for
      the practice of non-directive counselling, which aims at communicating
      information in a neutral, value-free way and thereby protecting patient autonomy.

PMID- 17209115
TI  - The problem of image interpretation in mammography: effects of lesion conspicuity
      on the visual search strategy of radiologists.
AB  - Radiologists make the decision to report or dismiss a possible cancer based not
      only on the finding itself, but also in the comparison with selected areas of the
      background. We examined the effects of fixating, for the first time, the location
      where the radiologist either reported the presence of a malignant mass or
      visually inspected the mass but did not report it, and the effects of pairing
      radiologists to read the same cases. Four experienced mammographers participated
      in this experiment. They read a set of 20 cases twice. Eye-position tracking was
      used to monitor the visual search behaviour of the observers. Spatial frequency
      analysis was used to determine the characteristics of the areas of the background
      fixated by the observers. Radiologists had more fixations in the cases where they
      agreed how to manage the lesion than when they disagreed. Correlation between the
      areas of the background sampled by the radiologists and an "average"
      representation of the background increased after the observers fixated for the
      first time a malignant mass that they reported. Fixating, for the first time, a
      location where the radiologist reports a malignant mass or a location containing
      a cancer that the radiologist visually inspects but decides not to report, has a
      significant effect on any further sampling of the background. Furthermore, care
      should be taken when pairing radiologists, because some observers showed such a
      similar visual search behaviour that not much would be gained by having them read
      the same cases.

PMID- 17209116
TI  - Improving mammographic decision accuracy by incorporating observer ratings with
      interpretation time.
AB  - Mammography is currently the most established technique for the early detection
      of breast cancer. However, mammography would benefit from further improvements as
      it does produce some errors, such as not finding all early-stage cancers. The
      objectives of this study were first, to measure the timing of correct and
      incorrect reading decisions in mammography and second, to exploit those
      dependencies to improve accuracy in mammographic interpretation. To address these
      objectives, an experiment was conducted where experienced breast imaging
      radiologists reviewed 400 mammographic regions equally divided among images that
      contained simulated benign masses, malignant masses, malignant
      microcalcifications and no lesions. The experiment recorded the radiologists'
      decision as well as the length of time the mammogram was interpreted in. The
      experiment results showed that incorrect detection as well as incorrect
      classification decisions were associated with longer interpretation times
      (p<0.0001). The timing results were used to create a model that would flag cases
      for review that had a higher probability of error. The flagged cases had a median
      accuracy drop of 13% for detection decisions and 16% for classification decisions
      compared with unflagged cases. This suggests that interpretation time can be
      incorporated into mammographic decision-making in order to identify cases with
      higher probabilities of perceptual error that require further review.

PMID- 17209117
TI  - Computer aided detection of masses in mammograms as decision support.
AB  - Performance of a computer aided detection (CAD) system for masses in mammograms
      was investigated. Using data collected in an observer study, in which experienced
      screening radiologists read a series of 500 screening mammograms without CAD,
      performance of radiologists was compared to the standalone performance of the CAD
      system. Due to a larger number of FPs (false positives), the performance of CAD
      was lower than that of the readers. However, when analysis was restricted to
      mammographic regions identified by the radiologists, it was found that the CAD
      system was comparable to the readers in discriminating these regions in cancer
      and non-cancer. In a retrospective analysis, the effect of independent
      combination of reader scores with CAD was compared to independent combination of
      scores of two radiologists. No significant difference was found between the
      results of these two methods. Both methods improved single reading results
      significantly.

PMID- 17209118
TI  - Breast screening: PERFORMS identifies key mammographic training needs.
AB  - The UK Breast Screening Programme has recently expanded the age range for
      invitation in the prevalent round to 70 years. In contrast, fewer radiologists
      now choose to specialise in the area of breast cancer screening. In response to
      this depletion in film-reading personnel, an increasing number of radiographers
      have been trained as advanced practitioners in order to film-read alongside the
      current radiologists. As part of the quality assurance programme for the National
      Health Service Breast Screening Programme (NHSBSP), each film-reader can
      participate in a voluntary self-assessment scheme (Personal Performance in
      Mammographic Screening, PERFORMS) which consists of a number of recent
      challenging breast screening cases that are amassed nationally and distributed bi
      annually. The scheme produces anonymous data on any areas of difficulties that
      individual participants have; these data can then be aggregated over groups of
      participants or over specific types of screening cases. In this paper, the areas
      of difficulty experienced by groups of advanced practitioners and radiologists on
      the PERFORMS cases were investigated to determine whether there were occupational
      group differences in reading skills in terms of case classification and feature
      type. Identifying if such problematic areas exist would be the first step to
      provide training sets specially tailored to the needs of particular occupational
      groups. As a bench mark for which cases could be problematic, the types of cases
      that a panel of experienced radiologists deemed as difficult was first examined
      in order to compare the performance of both film-reading groups against this
      panel standard. Secondly, any differences in performance error and case
      characteristics (classification, difficulty level and feature type) between
      radiologists and advanced practitioners were examined. The decisions of 15
      experienced "panel" radiologists and approximately 400 film readers (including
      radiologists and advanced practitioners) were compared on 180 cases, over a
      number of years. This study employed a matched design which controlled for any
      differences between radiologists and advanced practitioners in terms of real-life
      factors, such as volume of cases read per week and years of radiological
      experience. The results elucidate the type of cases most appropriate for advanced
      mammographic training. No significant differences were found between the advanced
      practitioners and radiologists on these self-assessment screening cases,
      indicating that dedicated occupational group training is not required.

PMID- 17209119
TI  - The reliability of measuring physical characteristics of spiculated masses on
      mammography.
AB  - The goal of this study was to assess the reliability of measurements of the
      physical characteristics of spiculated masses on mammography. The images used in
      this study were obtained from the Digital Database for Screening Mammography. Two
      experienced radiologists measured the properties of 21 images of spiculated
      masses. The length and width of all spicules and the major axis of the mass were
      measured. In addition, the observers counted the total number of spicules.
      Interobserver and intraobserver variability were evaluated using a hypothesis
      test for equivalence, the intraclass correlation coefficient (ICC) and Bland
      Altman statistics. For an equivalence level of 30% of the mean of the senior
      radiologist's measurement, equivalence was achieved for the measurements of
      average spicule length (p<0.01), average spicule width (p = 0.03), the length of
      the major axis (p<0.01) and for the count of the number of spicules (p<0.01).
      Similarly, with the ICC analysis technique "excellent" inter-rater agreement was
      observed for the measurements of average spicule length (ICC = 0.770), the length
      of the major axis (ICC = 0.801) and for the count of the number of spicules (ICC
      = 0.780). "Fair to good" agreement was observed for the average spicule width
      (ICC = 0.561). Equivalence was also demonstrated for intraobserver measurements.
      Physical properties of spiculated masses can be measured reliably on mammography.
      The interobserver and intraobserver variability for this task is comparable with
      that reported for other measurements made on medical images.

PMID- 17209120
TI  - Differential selection of acridine resistance mutations in human DNA
      topoisomerase IIbeta is dependent on the acridine structure.
AB  - Type II DNA topoisomerases are targets of acridine drugs. Nine mutations
      conferring resistance to acridines were obtained by forced molecular evolution,
      using methyl N-(4'-(9-acridinylamino)-3-methoxy-phenyl) methane sulfonamide
      (mAMSA), methyl N-(4'-(9-acridinylamino)-2-methoxy-phenyl) carbamate
      hydrochloride (mAMCA), methyl N-(4'-(9-acridinylamino)-phenyl) carbamate
      hydrochloride (AMCA), and N-[2-(dimethylamino)ethyl]acridines-4-carboxamide
      (DACA) as selection agents. Mutations betaH514Y, betaE522K, betaG550R, betaA596T,
      betaY606C, betaR651C, and betaD661N were in the B' domain, and betaG465D and
      betaP732L were not. With AMCA, four mutations were selected (betaE522K,
      betaG550R, betaA596T, and betaD661N). Two mutations were selected with mAMCA
      (betaY606C and betaR651C) and two with mAMSA (betaG465D and betaP732L). It is
      interesting that there was no overlap between mutation selection with AMCA and
      mAMSA or mAMCA. AMCA lacks the methoxy substituent present in mAMCA and mAMSA,
      suggesting that this motif determines the mutations selected. With the fourth
      acridine DACA, five mutations were selected for resistance (betaG465D, betaH514Y,
      betaG550R, betaA596T, and betaD661N). betaG465D was selected with both DACA and
      mAMSA, and betaG550R, betaA596T, and betaD661N were selected with both DACA and
      AMCA. DACA lacks the anilino motif of the other three drugs but retains the
      acridine ring motif. The overlap in selection with DACA and mAMSA or AMCA
      suggests that altered recognition of the acridine moiety may be involved in these
      mutations. We used restriction fragment length polymorphisms and heteroduplex
      analysis to demonstrate that some mutations were selected multiple times
      (betaG465D, betaE522K, betaG550R, betaA596T, and betaD661N), whereas others were
      selected only once (betaH514Y, betaY606C, betaR651C, and betaP732L). Here, we
      compare the drug resistance profile of all nine mutations and report the
      biochemical characterization of three, betaG550R, betaY606C, and betaD661N.

PMID- 17209121
TI  - Voltage-sensitive oxonol dyes are novel large-conductance Ca2+-activated K+
      channel activators selective for beta1 and beta4 but not for beta2 subunits.
AB  - The large-conductance Ca(2+)-activated K(+) (BK) channel is activated by both the
      increase of intracellular Ca(2+) concentration and membrane depolarization. The
      BK channel plays crucial roles as a key molecule in the negative feedback
      mechanism regulating membrane excitability and cellular Ca(2+) in various cell
      types. Here, we report that a widely used slow-response voltage-sensitive
      fluorescent dye, bis(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC(4)(3)],
      is a potent BK channel activator. The application of DiBAC(4)(3) at
      concentrations of 10 nM and higher significantly increased whole-cell BK channel
      currents in human embryonic kidney 293 cells expressing rat BK channel alpha and
      beta1 subunits (rBKalphabeta1). In the presence of 300 nM DiBAC(4)(3), the
      activation voltage of the BK channel current shifted to the negative direction by
      approximately 30 mV, but the single-channel conductance was not affected.
      DiBAC(4)(3) activated whole-cell rBKalphabeta1 and rBKalphabeta4 currents in the
      same concentration range but partially blocked rBKalphabeta2 currents. The BK
      channel alpha subunit alone and some other types of K(+) channels examined were
      not markedly affected by 1 microM DiBAC(4)(3). Structure-activity relationship
      analyses revealed that a set of oxo- and oxoanion-moieties in two 1,3
      dialkylbarbituric acids, which are conjugated by oligomethine, is the novel
      skeleton for the beta-subunit-selective BK channel-opening property of
      DiBAC(4)(3) and related oxonol compounds. This conjugated structure may be
      located stereochemically in one plane. These findings provide a molecular and
      structural basis for understanding the regulatory mechanism of BK channel
      activity by an auxiliary beta subunit and will be fundamental to the development
      of beta-selective BK channel openers.

PMID- 17209122
TI  - Structure and function analysis of CaMdr1p, a major facilitator superfamily
      antifungal efflux transporter protein of Candida albicans: identification of
      amino acid residues critical for drug/H+ transport.
AB  - We have cloned and overexpressed multidrug transporter CaMdr1p as a green
      fluorescent protein-tagged protein to show its capability to extrude drug
      substrates. The drug extrusion was sensitive to pH and energy inhibitors and
      displayed selective substrate specificity. CaMdr1p has a unique and conserved
      antiporter motif, also called motif C [G(X6)G(X3)GP(X2)GP(X2)G], in its
      transmembrane segment 5 (TMS 5). Alanine scanning of all the amino acids of the
      TMS 5 by site-directed mutagenesis highlighted the importance of the motif, as
      well as that of other residues of TMS 5, in drug transport. The mutant variants
      of TMS 5 were placed in four different categories. The first category had four
      residues, G244, G251, G255, and G259, which are part of the conserved motif C,
      and their substitution with alanine resulted in increased sensitivity to drugs
      and displayed impaired efflux of drugs. Interestingly, first category mutants,
      when replaced with leucine, resulted in more dramatic loss of drug resistance and
      efflux. Notwithstanding the location in the core motif, the second category
      included residues which are part of the motif, such as P260, and those which were
      not part of the motif, such as L245, W248, P256, and F262, whose substitution
      with alanine resulted in a severe loss of drug resistance and efflux. The third
      category included G263, which is a part of motif C, but unlike other conserved
      glycines, its replacement with alanine or leucine showed no change in the
      phenotype. The replacement of the remaining 11 residues of the fourth category
      did not result in any change. The putative helical wheel projection showed
      clustering of functionally critical residues to one side and thus suggests an
      asymmetric nature of TMS 5.

PMID- 17209123
TI  - Identification and characterization of MFA1, the gene encoding Candida albicans a
      factor pheromone.
AB  - In the opaque state, MTLa and MTLalpha strains of Candida albicans are able to
      mate, and this mating is directed by a pheromone-mediated signaling process. We
      have used comparisons of genome sequences to identify a C. albicans gene encoding
      a candidate a-specific mating factor. This gene is conserved in Candida
      dubliniensis and is similar to a three-gene family in the related fungus Candida
      parapsilosis but has extremely limited similarity to the Saccharomyces cerevisiae
      MFA1 (ScMFA1) and ScMFA2 genes. All these genes encode C-terminal CAAX box motifs
      characteristic of prenylated proteins. The C. albicans gene, designated CaMFA1,
      is found on chromosome 2 between ORF19.2165 and ORF19.2219. MFA1 encodes an open
      reading frame of 42 amino acids that is predicted to be processed to a 14-amino
      acid prenylated mature pheromone. Microarray analysis shows that MFA1 is poorly
      expressed in opaque MTLa cells but is induced when the cells are treated with
      alpha-factor. Disruption of this C. albicans gene blocks the mating of MTLa cells
      but not MTLalpha cells, while the reintegration of the gene suppresses this cell
      type-specific mating defect.

PMID- 17209124
TI  - Rice SCAMP1 defines clathrin-coated, trans-golgi-located tubular-vesicular
      structures as an early endosome in tobacco BY-2 cells.
AB  - We recently identified multivesicular bodies (MVBs) as prevacuolar compartments
      (PVCs) in the secretory and endocytic pathways to the lytic vacuole in tobacco
      (Nicotiana tabacum) BY-2 cells. Secretory carrier membrane proteins (SCAMPs) are
      post-Golgi, integral membrane proteins mediating endocytosis in animal cells. To
      define the endocytic pathway in plants, we cloned the rice (Oryza sativa) homolog
      of animal SCAMP1 and generated transgenic tobacco BY-2 cells expressing yellow
      fluorescent protein (YFP)-SCAMP1 or SCAMP1-YFP fusions. Confocal
      immunofluorescence and immunogold electron microscopy studies demonstrated that
      YFP-SCAMP1 fusions and native SCAMP1 localize to the plasma membrane and mobile
      structures in the cytoplasm of transgenic BY-2 cells. Drug treatments and
      confocal immunofluorescence studies demonstrated that the punctate cytosolic
      organelles labeled by YFP-SCAMP1 or SCAMP1 were distinct from the Golgi apparatus
      and PVCs. SCAMP1-labeled organelles may represent an early endosome because the
      internalized endocytic markers FM4-64 and AM4-64 reached these organelles before
      PVCs. In addition, wortmannin caused the redistribution of SCAMP1 from the early
      endosomes to PVCs, probably as a result of fusions between the two compartments.
      Immunogold electron microscopy with high-pressure frozen/freeze-substituted
      samples identified the SCAMP1-positive organelles as tubular-vesicular structures
      at the trans-Golgi with clathrin coats. These early endosomal compartments
      resemble the previously described partially coated reticulum and trans-Golgi
      network in plant cells.

PMID- 17209125
TI  - Arabidopsis WEE1 kinase controls cell cycle arrest in response to activation of
      the DNA integrity checkpoint.
AB  - Upon the incidence of DNA stress, the ataxia telangiectasia-mutated (ATM) and
      Rad3-related (ATR) signaling kinases activate a transient cell cycle arrest that
      allows cells to repair DNA before proceeding into mitosis. Although the ATM-ATR
      pathway is highly conserved over species, the mechanisms by which plant cells
      stop their cell cycle in response to the loss of genome integrity are unclear. We
      demonstrate that the cell cycle regulatory WEE1 kinase gene of Arabidopsis
      thaliana is transcriptionally activated upon the cessation of DNA replication or
      DNA damage in an ATR- or ATM-dependent manner, respectively. In accordance with a
      role for WEE1 in DNA stress signaling, WEE1-deficient plants showed no obvious
      cell division or endoreduplication phenotype when grown under nonstress
      conditions but were hypersensitive to agents that impair DNA replication. Induced
      WEE1 expression inhibited plant growth by arresting dividing cells in the G2
      phase of the cell cycle. We conclude that the plant WEE1 gene is not rate
      limiting for cycle progression under normal growth conditions but is a critical
      target of the ATR-ATM signaling cascades that inhibit the cell cycle upon
      activation of the DNA integrity checkpoints, coupling mitosis to DNA repair in
      cells that suffer DNA damage.

PMID- 17209127
TI  - Inhibition of UCP2 expression reverses diet-induced diabetes mellitus by effects
      on both insulin secretion and action.
AB  - Recent characterization of the ability of uncoupling protein 2 (UCP2) to reduce
      ATP production and inhibit insulin secretion by pancreatic beta-cells has placed
      this mitochondrial protein as a candidate target for therapeutics in diabetes
      mellitus. In the present study we evaluate the effects of short-term treatment of
      two animal models of type 2 diabetes mellitus with an antisense oligonucleotide
      to UCP2. In both models, Swiss mice (made obese and diabetic by a hyperlipidic
      diet) and ob/ob mice, the treatment resulted in a significant improvement in the
      hyperglycemic syndrome. This effect was due not only to an improvement of insulin
      secretion, but also to improved peripheral insulin action. In isolated pancreatic
      islets, the partial inhibition of UCP2 increased ATP content, followed by
      increased glucose-stimulated insulin secretion. This was not accompanied by
      increased expression of enzymes involved in protection against oxidative stress.
      The evaluation of insulin action in peripheral tissues revealed that the
      inhibition of UCP2 expression significantly improved insulin signal transduction
      in adipose tissue. In conclusion, short-term inhibition of UCP2 expression
      ameliorates the hyperglycemic syndrome in two distinct animal models of obesity
      and diabetes. Metabolic improvement is due to a combined effect on insulin
      producing pancreatic islets and in at least one peripheral tissue that acts as a
      target for insulin.

PMID- 17209126
TI  - The indeterminate gametophyte1 gene of maize encodes a LOB domain protein
      required for embryo Sac and leaf development.
AB  - Angiosperm embryo sac development begins with a phase of free nuclear division
      followed by cellularization and differentiation of cell types. The indeterminate
      gametophyte1 (ig1) gene of maize (Zea mays) restricts the proliferative phase of
      female gametophyte development. ig1 mutant female gametophytes have a prolonged
      phase of free nuclear divisions leading to a variety of embryo sac abnormalities,
      including extra egg cells, extra polar nuclei, and extra synergids. Positional
      cloning of ig1 was performed based on the genome sequence of the orthologous
      region in rice. ig1 encodes a LATERAL ORGAN BOUNDARIES domain protein with high
      similarity to ASYMMETRIC LEAVES2 of Arabidopsis thaliana. A second mutant allele
      of ig1 was identified in a noncomplementation screen using active Mutator
      transposable element lines. Homozygous ig1 mutants have abnormal leaf morphology
      as well as abnormal embryo sac development. Affected leaves have disrupted
      abaxial-adaxial polarity and fail to repress the expression of meristem-specific
      knotted-like homeobox (knox) genes in leaf primordia, causing a proliferative,
      stem cell identity to persist in these cells. Despite the superficial similarity
      of ig1-O leaves and embryo sacs, ectopic knox gene expression cannot be detected
      in ig1-O embryo sacs.

PMID- 17209128
TI  - The use of Raman microscopy to determine and localize vitamin E in biological
      samples.
AB  - Alpha-tocopherol (aT), the predominant form of vitamin E in mammals, is thought
      to prevent oxidation of polyunsaturated fatty acids. In the lung, aT is perceived
      to be accumulated in alveolar type II cells and secreted together with surfactant
      into the epithelial lining fluid. Conventionally, determination of aT and related
      compounds requires extraction with organic solvents. This study describes a new
      method to determine and image the distribution of aT and related compounds within
      cells and tissue sections using the light-scattering technique of Raman
      microscopy to enable high spatial as well as spectral resolution. This study
      compared the nondestructive analysis by Raman microscopy of vitamin E, in
      particular aT, in biological samples with data obtained using conventional HPLC
      analysis. Raman spectra were acquired at spatial resolutions of 2-0.8 microm.
      Multivariate analysis techniques were used for analyses and construction of
      corresponding maps showing the distribution of aT, alpha-tocopherol quinone
      (aTQ), and other constituents (hemes, proteins, DNA, and surfactant lipids). A
      combination of images enabled identification of colocalized constituents
      (heme/aTQ and aT/surfactant lipids). Our data demonstrate the ability of Raman
      microscopy to discriminate between different tocopherols and oxidation products
      in biological specimens without sample destruction. By enabling the visualization
      of lipid-protein interactions, Raman microscopy offers a novel method of
      investigating biological characterization of lipid-soluble compounds, including
      those that may be embedded in biological membranes such as aT.

PMID- 17209129
TI  - RNAi pathway is functional in peripheral nerve axons.
AB  - Recent observations demonstrated that translation of mRNAs may occur in axonal
      processes at sites that are long distances away from the neuronal perikaria.
      While axonal protein synthesis has been documented in several studies, the
      mechanism of its regulation remains unclear. The aim of this study was to
      investigate whether RNA interference (RNAi) may be one of the pathways that
      control local protein synthesis in axons. Here we show that sciatic nerve
      contains Argonaute2 nuclease, fragile X mental retardation protein, p100
      nuclease, and Gemin3 helicase-components of the RNA-induced silencing complex
      (RISC). Application of short-interfering RNAs against neuronal beta-tubulin to
      the sciatic nerve initiated RISC formation, causing a decrease in levels of
      neuronal beta-tubulin III mRNA and corresponding protein, as well as a
      significant reduction in retrograde labeling of lumbar motor neurons. Our
      observations indicate that RNAi is functional in peripheral mammalian axons and
      is independent from the neuronal cell body or Schwann cells. We introduce a
      concept of local regulation of axonal translation via RNAi.

PMID- 17209131
TI  - Mitotic recombination as evidence of alternative pathogenesis of gastrointestinal
      stromal tumours in neurofibromatosis type 1.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder resulting
      in the growth of a variety of tumours, and is inherited in an autosomal dominant
      pattern. Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that
      commonly harbour oncogenic mutations in KIT or PDGFRA and are thought to arise
      from the interstitial cells of Cajal (ICC; the pacemaker cells of the gut). AIM:
      To characterise two patients with NF1 and GISTs. METHODS: Two patients were
      genotyped for germline mutations in NF1. GISTs from both patients were genotyped
      for somatic mutations in KIT and PDGFRA. Loss of heterozygosity (LOH) of NF1 in
      one GIST was assessed by genotyping seven microsatellite markers spanning 2.39 Mb
      of the NF1 locus in the tumour and in genomic DNA. The known germline mutation in
      NF1 was confirmed in GIST DNA by sequencing. The copy number of the mutated NF1
      allele was determined by multiplex ligand-dependent probe amplification. RESULTS:
      GISTs from both patients were of wild type for mutations in KIT and PDGFRA. In
      the GIST with adequate DNA, all seven markers were informative and showed LOH at
      the NF1 locus; sequencing of NF1 from that GIST showed no wild-type sequence,
      suggesting that it was lost in the tumour. Multiplex ligand-dependent probe
      amplification analysis showed that two copies of all NF1 exons were present.
      CONCLUSIONS: This is the first evidence of mitotic recombination resulting in a
      reduction to homozygosity of a germline NF1 mutation in an NF1-associated GIST.
      We hypothesise that the LOH of NF1 and lack of KIT and PDGFRA mutations are
      evidence of an alternative pathogenesis in NF1-associated GISTs.

PMID- 17209130
TI  - 13q Deletion and central nervous system anomalies: further insights from
      karyotype-phenotype analyses of 14 patients.
AB  - BACKGROUND: Chromosome 13q deletion is associated with varying phenotypes, which
      seem to depend on the location of the deleted segment. Although various attempts
      have been made to link the 13q deletion intervals to distinct phenotypes, there
      is still no acknowledged consensus correlation between the monosomy of distinct
      13q regions and specific clinical features. METHODS: 14 Italian patients carrying
      partial de novo 13q deletions were studied. Molecular-cytogenetic
      characterisation was carried out by means of array-comparative genomic
      hybridisation (array-CGH) or fluorescent in situ hybridisation (FISH). RESULTS:
      Our 14 patients showed mental retardation ranging from profound-severe to
      moderate-mild: eight had central nervous system (CNS) anomalies, including neural
      tube defects (NTDs), six had eye abnormalities, nine had facial dysmorphisms and
      10 had hand or feet anomalies. The size of the deleted regions varied from 4.2 to
      75.7 Mb. CONCLUSION: This study is the first systematic molecular
      characterisation of de novo 13q deletions, and offers a karyotype-phenotype
      correlation based on detailed clinical studies and molecular determinations of
      the deleted regions. Analyses confirm that patients lacking the 13q32 band are
      the most seriously affected, and critical intervals have been preliminarily
      assigned for CNS malformations. Dose-sensitive genes proximal to q33.2 may be
      involved in NTDs. The minimal deletion interval associated with the Dandy-Walker
      malformation (DWM) was narrowed to the 13q32.2-33.2 region, in which the ZIC2 and
      ZIC5 genes proposed as underlying various CNS malformations are mapped.

PMID- 17209132
TI  - Associations of catalase gene polymorphisms with bone mineral density and bone
      turnover markers in postmenopausal women.
AB  - BACKGROUND: Oxidative stress has been recently suggested to play a part in the
      development of osteoporosis. Catalase is a major antioxidant enzyme that
      detoxifies hydrogen peroxide by converting it into water and oxygen, thereby
      preventing cellular injury by oxidative stress. AIMS: To examine the associations
      between the catalase gene (CAT) polymorphisms and bone mineral density (BMD) and
      bone turnover markers in postmenopausal Korean women. METHODS: All exons, their
      boundaries and the promoter region (approximately 1.5 kb) were directly sequenced
      in 24 individuals. Among 18 variants identified by a direct sequence method, four
      polymorphisms were selected and genotyped in all study participants (n = 560).
      BMD at the lumbar spine and proximal femur was measured using dual-energy x ray
      absorptiometry. Serum osteocalcin concentrations and bone-specific alkaline
      phosphatase activity were determined by an immunoradiometric assay and an
      immunoassay, respectively. RESULTS: The mean (standard deviation) age of the
      participants was 59.4 (7.2) years. Multivariate analysis showed an association of
      the +22348C-->T polymorphism with BMD at the lumbar spine (p = 0.01 in the
      dominant model) and at femur neck (p = 0.05 in the dominant model), and with
      serum osteocalcin level (p = 0.008 in the dominant model). Haplotype analyses
      showed that HT4 (-20T, +144C, +22348T, +33078A) was significantly associated with
      higher BMD at various sites (p<0.001-0.03) and with lower serum osteocalcin
      levels (p = 0.01 in the codominant model). CONCLUSIONS: These findings indicate
      that the +22348C-->T polymorphism and HT4 of CAT may be useful genetic markers
      for bone metabolism.

PMID- 17209133
TI  - Is alpha-T catenin (VR22) an Alzheimer's disease risk gene?
AB  - BACKGROUND: Recently, conflicting reports have been published on the potential
      role of genetic variants in the alpha-T catenin gene (VR22; CTNNA3) on the risk
      for Alzheimer's disease. In these papers, evidence for association is mostly
      observed in multiplex families with Alzheimer's disease, whereas case-control
      samples of sporadic Alzheimer's disease are predominantly negative. METHODS:
      After sequencing VR22 in multiplex families with Alzheimer's disease linked to
      chromosome 10q21, we identified a novel non-synonymous (Ser596Asn; rs4548513)
      single nucleotide polymorphism (SNP). This and four non-coding SNPs were assessed
      in two independent samples of families with Alzheimer's disease, one with 1439
      subjects from 437 multiplex families with Alzheimer's disease and the other with
      489 subjects from 217 discordant sibships. RESULTS: A weak association with the
      Ser596Asn SNP in the multiplex sample, predominantly in families with late-onset
      Alzheimer's disease (p = 0.02), was observed. However, this association does not
      seem to contribute substantially to the chromosome 10 Alzheimer's disease linkage
      signal that we and others have reported previously. No evidence was found of
      association with any of the four additional SNPs tested in the multiplex families
      with Alzheimer's disease. Finally, the Ser596Asn change was not associated with
      the risk for Alzheimer's disease in the independent discordant sibship sample.
      CONCLUSIONS: This is the first study to report evidence of an association between
      a potentially functional, non-synonymous SNP in VR22 and the risk for Alzheimer's
      disease. As the underlying effects are probably small, and are only seen in
      families with multiple affected members, the population-wide significance of this
      finding remains to be determined.

PMID- 17209134
TI  - Mutations in PLA2G6 and the riddle of Schindler disease.

PMID- 17209135
TI  - Activation of elastin transcription by transforming growth factor-beta in human
      lung fibroblasts.
AB  - Elastin synthesis is essential for lung development and postnatal maturation as
      well as for repair following injury. Using human embryonic lung fibroblasts that
      express undetectable levels of elastin as assessed by Northern analyses, we found
      that treatment with exogenous transforming growth factor-beta (TGF-beta) induced
      rapid and transient increases in levels of elastin heterogeneous nuclear RNA
      (hnRNA) followed by increases of elastin mRNA and protein expression. In
      fibroblasts derived from transgenic mice, TGF-beta induced increases in the
      expression of a human elastin gene promoter fragment driving a chloramphenicol
      acetyl transferase reporter gene. The induction of elastin hnRNA and mRNA
      expression by TGF-beta was abolished by pretreatments with TGF-beta receptor I
      inhibitor, global transcription inhibitor actinomycin D, and partially blocked by
      addition of protein synthesis inhibitor cycloheximide, but was not affected by
      the p44/42 MAPK inhibitor U0126. Pretreatment with the p38 MAPK inhibitor SB
      203580 also partially attenuated the levels of TGF-beta-induced elastin mRNA but
      not its hnRNA. Western analysis indicated that TGF-beta stimulated Akt
      phosphorylation. Inhibition of phosphatidylinositol 3-kinase and Akt
      phosphorylation by LY-294002 abolished TGF-beta-induced increases in elastin
      hnRNA and mRNA expression. Treatment of lung fibroblasts with interleukin-1beta
      or the histone deacetylase inhibitor trichostatin A inhibited TGF-beta-induced
      elastin mRNA and hnRNA expression by a mechanism that involved inhibition of Akt
      phosphorylation. Downregulation of Akt2 but not Akt1 expression employing small
      interfering RNA duplexes blocked TGF-beta-induced increases of elastin hnRNA and
      mRNA levels. Together, our results demonstrated that TGF-beta activates elastin
      transcription that is dependent on phosphatidylinositol 3-kinase/Akt activity.

PMID- 17209136
TI  - Inhibition of hypoxia-induced calcium responses in pulmonary arterial smooth
      muscle by acetazolamide is independent of carbonic anhydrase inhibition.
AB  - Hypoxic pulmonary vasoconstriction (HPV) occurs with ascent to high altitude and
      can contribute to development of high altitude pulmonary edema (HAPE). Vascular
      smooth muscle contains carbonic anhydrase (CA), and acetazolamide (AZ), a CA
      inhibitor, blunts HPV and might be useful in the prevention of HAPE. The
      mechanism by which AZ impairs HPV is uncertain. Originally developed as a
      diuretic, AZ also has direct effects on systemic vascular smooth muscle,
      including modulation of pH and membrane potential; however, the effect of AZ on
      pulmonary arterial smooth muscle cells (PASMCs) is unknown. Since HPV requires
      Ca2+ influx into PASMCs and can be modulated by pH, we hypothesized that AZ
      alters hypoxia-induced changes in PASMC intracellular pH (pH(i)) or Ca2+
      concentration ([Ca2+](i)). Using fluorescent microscopy, we tested the effect of
      AZ as well as two other potent CA inhibitors, benzolamide and ethoxzolamide,
      which exhibit low and high membrane permeability, respectively, on hypoxia
      induced responses in PASMCs. Hypoxia caused a significant increase in [Ca2+](i)
      but no change in pH(i). All three CA inhibitors slightly decreased basal pH(i),
      but only AZ caused a concentration-dependent decrease in the [Ca2+](i) response
      to hypoxia. AZ had no effect on the KCl-induced increase in [Ca2+](i) or membrane
      potential. N-methyl-AZ, a synthesized compound lacking the unsubstituted
      sulfonamide group required for CA inhibition, had no effect on pH(i) but
      inhibited hypoxia-induced Ca2+ responses. These results suggest that AZ
      attenuates HPV by selectively inhibiting hypoxia-induced Ca2+ responses via a
      mechanism independent of CA inhibition, changes in pH(i), or membrane potential.

PMID- 17209137
TI  - Expression and localization of surfactant proteins in human nasal epithelium.
AB  - Surfactant proteins (SPs), designated SP-A, SP-B, SP-C, and SP-D, play an
      important role in surfactant metabolism and host defense mechanisms in the lung.
      This study investigates expression of the different SP types in human nasal
      mucosa and cultured normal human nasal epithelial (NHNE) cells and whether the
      expression of SP mRNA is influenced by the degree of mucociliary differentiation.
      RT-PCR was performed with mRNA from cultured NHNE cells and nasal mucosa.
      Immunohistochemical staining for SPs was performed on nasal mucosa specimens.
      Western blot analysis was performed on cell lysates from cultured NHNE cells. SP
      A2, SP-B, and SP-D mRNAs were expressed in normal NHNE cells and human nasal
      mucosa. SPs were localized in ciliated cells of the surface epithelium and serous
      acini of the submucosal glands. SP-A, SP-B, and SP-D proteins were expressed in
      cultured NHNE cells. The degree of mucociliary differentiation influenced
      expression of the SP gene. We demonstrate that SP-A, SP-B, and SP-D are expressed
      in human nasal mucosa and cultured NHNE cells. Further study of the functional
      role of SPs in the upper airway is required.

PMID- 17209138
TI  - Hydrogen sulfide acts as an inflammatory mediator in cecal ligation and puncture
      induced sepsis in mice by upregulating the production of cytokines and chemokines
      via NF-kappaB.
AB  - Recent studies have implied that hydrogen sulfide (H2S) plays a crucial role in
      several inflammatory conditions. However, so far little is known about the
      mechanism by which H2S provokes the inflammatory response in sepsis. Thus the aim
      of this study was to investigate if H2S regulates sepsis-associated systemic
      inflammation and production of proinflammatory mediators via the activation of NF
      kappaB. Male Swiss mice were subjected to cecal ligation and puncture (CLP)
      induced sepsis and treated with dl-propargylglycine (PAG; 50 mg/kg ip), NaHS (10
      mg/kg ip), or saline. PAG, an inhibitor of H2S formation, was administered either
      1 h before or 1 h after CLP, whereas NaHS, an H2S donor, was given at the time of
      CLP. Some normal mice were given NaHS (10 mg/kg ip) to induce lung inflammation
      with or without pretreatment with the NF-kappaB inhibitor BAY 11-7082. Eight
      hours after CLP, both prophylactic and therapeutic administration of PAG
      significantly reduced the mRNA and protein levels of IL-1beta, IL-6, TNF-alpha,
      monocyte chemotactic protein-1, and macrophage inflammatory protein-2 in lung and
      liver coupled with decreased activation and translocation of NF-kappaB in lung
      and liver. Inhibition of H2S formation also significantly reduced lung
      permeability and plasma alanine aminotransferase activity. In contrast, injection
      of NaHS significantly aggravated sepsis-associated systemic inflammation and
      increased NF-kappaB activation. In addition, H2S-induced lung inflammation was
      blocked by BAY 11-7082. Therefore, H2S upregulates the production of
      proinflammatory mediators and exacerbates the systemic inflammation in sepsis
      through a mechanism involving NF-kappaB activation.

PMID- 17209139
TI  - Hyperoxia reduces bone marrow, circulating, and lung endothelial progenitor cells
      in the developing lung: implications for the pathogenesis of bronchopulmonary
      dysplasia.
AB  - Hyperoxia disrupts vascular and alveolar growth of the developing lung and
      contributes to the development of bronchopulmonary dysplasia (BPD). Endothelial
      progenitor cells (EPC) have been implicated in repair of the vasculature, but
      their role in lung vascular development is unknown. Since disruption of vascular
      growth impairs lung structure, we hypothesized that neonatal hyperoxia impairs
      EPC mobilization and homing to the lung, contributing to abnormalities in lung
      structure. Neonatal mice (1-day-old) were exposed to 80% O(2) at Denver's
      altitude (= 65% at sea level) or room air for 10 days. Adult mice were also
      exposed for comparison. Blood, lung, and bone marrow were harvested after
      hyperoxia. Hyperoxia decreased pulmonary vascular density by 72% in neonatal but
      not adult mice. In contrast to the adult, hyperoxia simplified distal lung
      structure neonatal mice. Moderate hyperoxia reduced EPCs (CD45-/Sca
      1+/CD133+/VEGFR-2+) in the blood (55%; P < 0.03), bone marrow (48%; P < 0.01),
      and lungs (66%; P < 0.01) of neonatal mice. EPCs increased in bone marrow (2.5
      fold; P < 0.01) and lungs (2-fold; P < 0.03) of hyperoxia-exposed adult mice.
      VEGF, nitric oxide (NO), and erythropoietin (Epo) contribute to mobilization and
      homing of EPCs. Lung VEGF, VEGF receptor-2, endothelial NO synthase, and Epo
      receptor expression were reduced by hyperoxia in neonatal but not adult mice. We
      conclude that moderate hyperoxia decreases vessel density, impairs lung
      structure, and reduces EPCs in the circulation, bone marrow, and lung of neonatal
      mice but increases EPCs in adults. This developmental difference may contribute
      to the increased susceptibility of the developing lung to hyperoxia and may
      contribute to impaired lung vascular and alveolar growth in BPD.

PMID- 17209140
TI  - Cigarette smoke-induced blockade of the mitochondrial respiratory chain switches
      lung epithelial cell apoptosis into necrosis.
AB  - Increased lung cell apoptosis and necrosis occur in patients with chronic
      obstructive pulmonary disease (COPD). Mitochondria are crucially involved in the
      regulation of these cell death processes. Cigarette smoke is the main risk factor
      for development of COPD. We hypothesized that cigarette smoke disturbs
      mitochondrial function, thereby decreasing the capacity of mitochondria for ATP
      synthesis, leading to cellular necrosis. This hypothesis was tested in both human
      bronchial epithelial cells and isolated mitochondria. Cigarette smoke extract
      exposure resulted in a dose-dependent inhibition of complex I and II activities.
      This inhibition was accompanied by decreases in mitochondrial membrane potential,
      mitochondrial oxygen consumption, and production of ATP. Cigarette smoke extract
      abolished the staurosporin-induced caspase-3 and -7 activities and induced a
      switch from epithelial cell apoptosis into necrosis. Cigarette smoke induced
      mitochondrial dysfunction, with compounds of cigarette smoke acting as blocking
      agents of the mitochondrial respiratory chain; loss of ATP generation leading to
      cellular necrosis instead of apoptosis is a new pathophysiological concept of
      COPD development.

PMID- 17209141
TI  - Inhibition of JNK activation prolongs survival after smoke inhalation from fires.
AB  - Initial injury from smoke inhalation is mainly to the trachea and bronchi and is
      characterized by mucosal hyperemia and increased microvascular permeability,
      exfoliation of epithelial lining, mucous secretion, mucous plugging, and an acute
      inflammatory cell influx. In this study, we explore the role of the c-Jun N
      terminal protein kinase (JNK) pathway in smoke inhalation lung injury using a rat
      model of exposure to smoke from burning cotton. Male Sprague-Dawley rats were
      exposed to smoke from burning cotton for 15 min, and 1 h after injury a JNK
      inhibitor (SP-600125) or vehicle was injected. We measured neutrophil influx,
      cytokine release, percent of apoptotic cells, airway plugging, and survival.
      Administration of a JNK inhibitor 1 h after smoke inhalation decreased airway
      apoptosis, mucous plugging, influx of inflammatory cells, and the release of
      cytokines and significantly prolonged animal survival (P < 0.05). These in vivo
      data show that the JNK pathway plays a critical role in smoke-induced lung injury
      and offer an attractive therapeutic approach for this injury.

PMID- 17209142
TI  - Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes.
AB  - Gene-gene interaction analyses have been suggested as a potential strategy to
      help identify common disease susceptibility genes. Recently, evidence of a
      statistical interaction between polymorphisms in two negative immunoregulatory
      genes, CBLB and CTLA4, has been reported in type 1 diabetes (T1D). This study, in
      480 Danish families, reported an association between T1D and a synonymous coding
      SNP in exon 12 of the CBLB gene (rs3772534 G>A; minor allele frequency, MAF=0.24;
      derived relative risk, RR for G allele=1.78; P=0.046). Furthermore, evidence of a
      statistical interaction with the known T1D susceptibility-associated CTLA4
      polymorphism rs3087243 (laboratory name CT60, G>A) was reported (P<0.0001), such
      that the CBLB SNP rs3772534 G allele was overtransmitted to offspring with the
      CTLA4 rs3087243 G/G genotype. We have, therefore, attempted to obtain additional
      support for this finding in both large family and case-control collections. In a
      primary analysis, no evidence for an association of the CBLB SNP rs3772534 with
      disease was found in either sample set (2162 parent-child trios, P=0.33; 3453
      cases and 3655 controls, P=0.69). In the case-only statistical interaction
      analysis between rs3772534 and rs3087243, there was also no support for an effect
      (1994 T1D affected offspring, and 3215 cases, P=0.92). These data highlight the
      need for large, well-characterized populations, offering the possibility of
      obtaining additional support for initial observations owing to the low prior
      probability of identifying reproducible evidence of gene-gene interactions in the
      analysis of common disease-associated variants in human populations.

PMID- 17209143
TI  - Potential medical and surgical complications of serotonergic antidepressant
      medications.
AB  - Serotonergic antidepressants are the most widely used group of antidepressant
      medications. Although generally considered to have a favorable adverse-effect
      profile, serotonergic antidepressants are associated with potentially dangerous
      medical complications, some of which have only recently become apparent to
      patients and clinicians. This article reviews the association of serotonergic
      antidepressants and the following medical complications: syndrome of
      inappropriate antidiuretic hormone secretion, bleeding, serotonin syndrome,
      serotonin-discontinuation syndrome, and adverse pregnancy and neonatal effects.
      Physicians need to remain aware of these potential medical complications and
      integrate this information into their clinical decision-making, informed-consent
      process, baseline assessment, and follow-up monitoring.

PMID- 17209144
TI  - DNR versus DNT: clinical implications of a conceptual ambiguity: a case analysis.
AB  - Psychiatrists who practice psychosomatic medicine are routinely called upon to
      help resolve ethical dilemmas that arise in the care of patients near the end of
      their lives. Psychosomatic-medicine psychiatrists may be of unique value in these
      situations because of the clinical insights that we bring to the care of the
      dying patient. In particular, our subspecialty brings expertise related to the
      evaluation of decisional capacity of patients who are faced with accepting or
      declining end-of-life clinical interventions, such as resuscitation and
      intubation. In this first entry in a new bioethics case series in Psychosomatics,
      we will lay the groundwork for examining a complex patient case and provide an
      illustrative analysis of the end-of-life care issues that may be addressed by
      psychiatrists who practice psychosomatic medicine.

PMID- 17209145
TI  - A practical screening tool for anxiety and depression in patients with chronic
      breathing disorders.
AB  - Obstructive lung diseases are associated with high rates of depression and
      anxiety, yet many patients are never screened or treated. This study evaluated
      the five-question Depression and Anxiety modules of the Primary Care Evaluation
      of Mental Disorders (PRIME-MD) Patient Questionnaire as a telephone screen in
      1,632 patients with chronic breathing disorders at a Veterans Affairs Medical
      Center in Houston, TX. Subsequent testing of 828 patients with the Beck
      Depression Inventory-II and the Beck Anxiety Inventory showed that the
      sensitivity and specificity, respectively, of the Depression and Anxiety modules
      of the PRIME-MD Patient Questionnaire screening were 94.6% and 49.5%
      (Depression); 93.7% and 32.2% (Anxiety); and 97.7%, and 36.0% (combined screen),
      with an overall accuracy of 80.7%. In such populations, these two modules of the
      PRIME-MD Patient Questionnaire may be a useful screening tool.

PMID- 17209146
TI  - Effects of antidepressant treatment on cognitive performance in elderly subjects
      with heart failure and comorbid major depression: an exploratory study.
AB  - Cognitive deficits are common in association with heart failure (HF), and it is
      possible that their severity is magnified by the concomitant presence of major
      depressive disorder (MDD). Using the Cambridge Mental Disorders of the Elderly
      Examination battery, the authors compared the cognitive performance of MDD-HF
      subjects (N=20), nondepressed HF subjects (N=23), and healthy control subjects
      (N=18). Scores were lower in both HF groups relative to control subjects. In the
      MDD-HF group, there were significant cognitive improvements after antidepressant
      treatment. Cognitive impairment is, therefore, significant in HF subjects with or
      without comorbid MDD, and it is important to recognize and treat MDD symptoms
      associated with HF.

PMID- 17209147
TI  - Prevalence of HIV infection in a general psychiatric outpatient population.
AB  - The prevalence of human immunodeficiency virus (HIV) infection in the general
      psychiatric population is unknown. The authors conducted a retrospective review
      of all patients evaluated through the psychiatric outpatient clinics at Duke
      University Medical Center from 2001 to 2004 in order to determine the prevalence
      of comorbid HIV infection and mental illness. HIV infection was present in 1.2%
      of the psychiatric outpatients, approximately four times the occurrence of HIV
      infection in the general adult population of the United States. The major
      psychiatric diagnostic categories with a high prevalence of HIV infection were
      substance abuse disorders (5%), personality disorders (3.1%), bipolar disorders
      (2.6%), and posttraumatic stress disorder (2.1%).

PMID- 17209148
TI  - Short-term stability of diagnoses of major and minor depression in older medical
      inpatients.
AB  - The authors sought to determine the short-term stability of diagnoses of major
      and minor depression in older medical inpatients. The investigation was a test
      retest design involving comparisons between different pairs of interviewers who
      assessed patients independently on medical wards of two acute-care, university
      affiliated hospitals by use of the Diagnostic Interview Schedule (DIS) at
      intervals between 1 and 51 days. Patients were 380 cognitively-intact patients
      age > or =65, assessed twice with the DIS. Core depressive symptoms (depressed
      mood, loss of interest or pleasure) were more stable than the other depressive
      symptoms. The presence of moderate-to-severe depressive symptoms, moderate-to
      severe disability, and depression symptoms of > or =6 months' duration were
      associated with a higher short-term stability of diagnosis. Age, gender,
      language, education, rater, interval between assessments, baseline number of
      medications, medical comorbidity, severity of medical illness, acute physiology
      score, and cognitive functioning were not associated with short-term depression
      stability. Stability of diagnosis may be improved by emphasis on core depressive
      symptoms or the presence of more severe depressive symptoms, moderate-to-severe
      disability, and duration of symptoms > or =6 months.

PMID- 17209149
TI  - Spanish perspective on enlarging a small specialty: the national research network
      for liaison psychiatry and psychosomatics.
AB  - The Spanish Research Network in Liaison Psychiatry and Psychosomatics (REPEP)
      comprises 11 centers (nodes), and was one of the successful applicants in a very
      competitive call for a networking program for the National Institute of Health
      "Carlos III" project. This article describes its general objectives and strategic
      plans. Both qualitative and quantitative results support our statement that this
      "perspective" should help to enlarge what is presently a small specialty.
      Synergies in the network have been potentiated; an ambitious national study on
      depressive comorbidity in complex medical patients has been executed; and new
      research and training programs have been initiated.

PMID- 17209150
TI  - Self-reported depression and cardiovascular risk factors in a community sample of
      women.
AB  - The authors examined data collected from a randomly selected, representative
      sample of 755 women (ages 23-97 years) from southeastern Australia. Self-report
      questionnaires were utilized to determine lifetime rates of depression and
      cardiovascular risk factors within the study sample. A lifetime history of
      depression (LHx) was reported by 145 women (19.20%). There were no associations
      between indices of weight, cholesterol levels, hypertension, inactivity,
      diabetes, and LHx. However, a history of smoking increased the odds of reporting
      an LHx, whereas women with self-reported angina were more than four times more
      likely to report an age-adjusted LHx.

PMID- 17209151
TI  - Frequency of ICD-10 factitious disorder: survey of senior hospital consultants
      and physicians in private practice.
AB  - The authors surveyed physicians for frequency estimates of factitious disorder
      among their patients. Twenty-six physicians in independent practice and 83 senior
      hospital consultants in internal medicine, surgery, neurology, and dermatology
      participated. They completed a questionnaire including the estimated 1-year
      prevalence of factitious disorder among their patients. Frequency estimates
      averaged 1.3% (0.0001%-15%). The number of patients treated correlated negatively
      with frequency estimates. Dermatologists and neurologists gave the highest
      estimations. One-third of the physicians rated themselves as insufficiently
      informed. Frequency estimations did not differ by information level. The
      estimated frequency is substantial and comparable to earlier findings. Authors
      discuss clinical implications.

PMID- 17209152
TI  - Manic delirium associated with clomiphene-induced ovulation.

PMID- 17209153
TI  - Affective disorder and personality change in a patient with traumatic brain
      injury.

PMID- 17209154
TI  - Factitious ovarian cancer: feigning via resources on the internet.

PMID- 17209155
TI  - Catatonic coma with profound bradycardia.
AB  - Catatonia may be monosymptomatic at presentation, with stupor or coma as the
      cardinal and only manifestation. A case of catatonic coma with profound
      bradycardia is presented to help clinicians recognize this entity and include
      catatonia in the differential diagnosis of coma as a rare etiology after other
      more common causes of coma have been excluded. Cases of catatonic coma are
      nevertheless important to identify because treatment with intravenous
      benzodiazepines is simple and highly effective. The authors argue that the
      descriptive term "catatonic coma" is preferable over terms implying
      psychogenesis, such as "psychogenic" or "hysterical" coma; for catatonia, the
      authors have a specific treatment, in the form of benzodiazepines; for
      "psychogenesis," there is none.

PMID- 17209156
TI  - Gastrointestinal medications.
AB  - Medications to address gastrointestinal disorders are among the most commonly
      dispensed somatic medications. The authors examine proton pump inhibitors, H(2)
      blockers, 5-HT(3) receptor-antagonists, and a few other drugs that are used to
      address this domain of medical concerns. The metabolic pathways, interactions
      with the P-glycoprotein transporter, and capabilities of inhibiting or inducing
      metabolic enzymes are elucidated for each drug. Specific drug-drug interactions
      with each agent are also detailed, including both psychotropic and non
      psychotropic agents. Also, the article explores how different genotypic variants
      for specific cytochrome P450 enzymes have an impact on the effectiveness and
      likelihood of drug-drug interactions relating to specific gastro-intestinal
      medications.

PMID- 17209157
TI  - Exacerbation of Psychogenic Movement Disorder by Interferon{alpha} Treatment of
      Hepatitis C.

PMID- 17209158
TI  - Exacerbation of psychotic symptoms associated with gatifloxacin.

PMID- 17209159
TI  - Dopamine does not limit fetal cerebrovascular responses to hypoxia.
AB  - Dopamine is used clinically to stabilize mean arterial blood pressure (MAP) in
      sick infants. One goal of this therapeutic intervention is to maintain adequate
      cerebral blood flow (CBF) and perfusion pressure. High-dose intravenous dopamine
      has been previously demonstrated to increase cerebrovascular resistance (CVR) in
      near-term fetal sheep. We hypothesized that this vascular response might limit
      cerebral vasodilatation during acute isocapnic hypoxia. We studied nine near-term
      chronically catheterized unanesthetized fetal sheep. Using radiolabeled
      microspheres to measure fetal CBF, we calculated CVR at baseline, during fetal
      hypoxia, and then with the addition of an intravenous dopamine infusion at 2.5,
      7.5, and 25 microg.kg(-1).min(-1) while hypoxia continued. During acute isocapnic
      fetal hypoxia, CBF increased 73.0 +/- 14.1% and CVR decreased 38.9 +/- 4.9% from
      baseline. Dopamine infusion at 2.5 and 7.5 microg.kg(-1).min(-1), begun during
      hypoxia, did not alter CVR or MAP, but MAP increased when dopamine infusion was
      increased to 25 microg.kg(-1).min(-1). Dopamine did not alter CBF or affect the
      CBF response to hypoxia at any dose. However, CVR increased at a dopamine
      infusion rate of 25 microg.kg(-1).min(-1). This increase in CVR at the highest
      dopamine infusion rate is likely an autoregulatory response to the increase in
      MAP, similar to our previous findings. Therefore, in chronically catheterized
      unanesthetized near-term fetal sheep, dopamine does not alter the expected
      cerebrovascular responses to hypoxia.

PMID- 17209160
TI  - Increased metaboreceptor stimulation explains the exaggerated exercise pressor
      reflex seen in heart failure.

PMID- 17209163
TI  - Increased mechanoreceptor/metaboreceptor stimulation explains the exaggerated
      exercise pressor reflex seen in heart failure.

PMID- 17209164
TI  - Sciatica: treatment with intradiscal and intraforaminal injections of steroid and
      oxygen-ozone versus steroid only.
AB  - PURPOSE: To prospectively compare the clinical effectiveness of intraforaminal
      and intradiscal injections of a mixture of a steroid, a local anesthetic, and
      oxygen-ozone (O(2)-O(3)) (chemodiscolysis) versus intraforaminal and intradiscal
      injections of a steroid and an anesthetic in the management of radicular pain
      related to acute lumbar disk herniation. MATERIALS AND METHODS: Medical Ethical
      Committee approval and informed consent were obtained. One hundred fifty-nine
      patients (86 men, 73 women; age range, 18-71 years) were included and were
      randomly assigned to two groups. Seventy-seven patients (group A) underwent
      intradiscal and intraforaminal injections of a steroid and an anesthetic, and 82
      patients (group B) underwent the same treatment with the addition of an O(2)-O(3)
      mixture. Procedures were performed with computed tomographic guidance. An
      Oswestry Low Back Pain Disability Questionnaire was administered before treatment
      and at intervals, the last at 6-month follow-up. Patients and clinicians were
      blinded as to which treatment was performed. Results were compared with the
      chi(2) test. RESULTS: After 6 months, treatment was successful in 36 (47%)
      patients in group A and in 61 (74%) patients in group B. The difference was
      significant (P < .01). CONCLUSION: Intraforaminal and intradiscal injections of a
      steroid, an anesthetic, and O(2)-O(3) are more effective at 6 months than
      injections of only a steroid and an anesthetic in the same sites.

PMID- 17209165
TI  - Medial collateral ligament complex of the ankle: MR appearance in asymptomatic
      subjects.
AB  - PURPOSE: To prospectively characterize the spin-echo magnetic resonance (MR)
      imaging appearance of the medial collateral ligament (MCL) complex of the ankle
      in asymptomatic volunteers. MATERIALS AND METHODS: The study was approved by
      institutional review board. Informed consent was obtained. MR images in 56
      asymptomatic subjects (29 women, 27 men; mean age, 40.7 years; range, 23-60
      years) were analyzed by two musculoskeletal radiologists. Visibility and signal
      intensity characteristics were analyzed for deep (anterior and posterior
      tibiotalar ligaments [TTLs]) and superficial (tibionavicular ligament [TNL],
      tibiospring ligament [TSL], and tibiocalcaneal ligament [TCL]) components of the
      MCL complex. Thickness of ligaments was compared between sexes (Mann-Whitney U
      test). Associations between age and variables of signal intensity characteristics
      and morphology were evaluated with Kruskal-Wallis test. RESULTS: Anterior and
      posterior TTLs, TNL, TSL, and TCL were visible in 31 (55%), 56 (100%), 31 (55%),
      56 (100%), and 49 (88%) subjects, respectively. On T1-weighted images, anterior
      and posterior TTLs, TNL, TSL, and TCL were more commonly of intermediate signal
      intensity than hypointense (77%, 100%, 93%, 50%, and 73% of subjects,
      respectively); on T2-weighted images, they were commonly hypointense (55%, 52%,
      42%, 75%, and 78% of subjects, respectively). On T2-weighted images, posterior
      TTL had a striated appearance that was significantly associated with age (P =
      .004) in 89% of subjects: In subjects younger than 45 years, this striated
      appearance was present. On T1-weighted images, striation was present in 48% of
      subjects. Striation was uncommon in remaining ligaments. Mean thickness and range
      were 1.5 mm and 1-4 mm (anterior TTL), 8.2 mm and 6-11 mm (posterior TTL), 1.6 mm
      and 1-2 mm (TNL), 2.0 mm and 1-4 mm (TSL), and 1.2 mm and 1-3 mm (TCL). TNL (P =
      .001) and TSL (P = .003) were significantly thicker in men than in women.
      CONCLUSION: In asymptomatic volunteers, posterior TTL and TSL were always
      visible, but anterior TTL and TNL are only seen in approximately half of
      subjects. Posterior TTL has a typically striated appearance.

PMID- 17209166
TI  - Quantitative assessment of glomerular filtration rate with MR gadolinium slope
      clearance measurements: a phase I trial.
AB  - PURPOSE: To prospectively demonstrate the feasibility of quantifying the
      glomerular filtration rate (GFR) by assessing the renal clearance of gadolinium
      based contrast medium from the extracellular fluid volume in healthy volunteers.
      MATERIALS AND METHODS: The study was approved by the ethics committee and the
      governmental drug administration department (registration number 4030139, EudraCT
      number 2004-002969-20, study protocol number 318/2004). Informed consent was
      obtained from 16 healthy volunteers (six female, 10 male; mean age, 24.5 years +/
      2.8 [standard deviation]). Thirteen volunteers (four women, nine men; mean age,
      24.8 years +/- 2.7; range, 23-30 years) successfully contributed to the study.
      The GFR was assessed by recording the renal clearance of gadobutrol (3.75 mL,
      approximately 0.05 mmol per kilogram of body weight) at navigator-gated turbo
      fast low-angle shot magnetic resonance (MR) imaging. Time-signal intensity curves
      were constructed from manually drawn regions of interest in the liver, spleen,
      and renal cortex, and the GFR was calculated by using exponential fitting.
      Simultaneously obtained iopromide clearance measurements were the reference
      standard. Statistical evaluations included Bland-Altman plotting and analysis of
      the relative deviation from iopromide clearance. RESULTS: Evaluation of liver
      regions of interest revealed the lowest mean of paired differences from the
      iopromide clearance measurements (-5.9 mL/min per 1.73 m(2) +/- 14.6), with a
      mean GFR of 109.0 mL/min per 1.73 m(2) +/- 17.1 (134.1 mL/min per 1.73 m(2) +/-
      35.4 for spleen, 100.7 mL/min per 1.73 m(2) +/- 25.1 for renal cortex) compared
      with a mean GFR of 103.1 mL/min per 1.73 m(2) +/- 9.4 measured by using iopromide
      clearance. The maximum deviation of MR-determined gadobutrol clearance values
      from iopromide clearance values was 29.2%. The mean disposition half-life of
      gadobutrol measured in the liver was 83.0 minutes +/- 14.2 (72.4 minutes +/- 20.2
      in spleen, 92.6 minutes +/- 23.7 in renal cortex). CONCLUSION: The described MR
      imaging method enables absolute quantification of the GFR after routine contrast
      material-enhanced MR imaging.

PMID- 17209167
TI  - Irreversible myocardial injury: assessment with cardiovascular delayed
      enhancement MR imaging and comparison of 1.5 and 3.0 T--initial experience.
AB  - PURPOSE: To prospectively compare visualization and quantification of
      irreversible myocardial injury in patients with chronic myocardial infarction at
      1.5- and 3.0-T magnetic resonance (MR) imaging. MATERIALS AND METHODS: The
      institutional research ethics committee approved the study. Participants gave
      written informed consent. Sixteen male patients (mean age, 66 years +/- 13
      [standard deviation]) with myocardial infarction were imaged with the same
      sequence by the same operator at 1.5 and 3.0 T. After cine imaging, a bolus of
      gadodiamide was administered. Short-axis images of entire left ventricle (LV)
      were acquired with a breath-hold T1-weighted segmented inversion-recovery turbo
      fast low-angle shot (FLASH) sequence. Agreement for myocardial hyperenhancement
      (HE) mass between field strengths was assessed with Bland-Altman method;
      agreement for detection and transmural extent of HE was assessed with kappa
      statistics. Intra- and interobserver reproducibility of mass and transmural
      extent of HE were assessed at 1.5 and 3.0 T. RESULTS: Bland-Altman analysis
      revealed no systematic bias (mean difference, 0.2 g; 95% confidence interval: 
      0.7 g, 1.2 g) and acceptable limits of agreement (-3.3 to 3.8 g) between field
      strengths for HE mass. HE mass measurements were strongly correlated (R(2) =
      0.99); there was no significant difference in measurements at 1.5 and 3.0 T (28.1
      g +/- 15.7 [22.6% +/- 10.9 of LV mass] vs 27.8 g +/- 15.7 [22.3% +/- 10.7 of LV
      mass], respectively; P = .599). For all segments, there was a high degree of
      agreement for HE detection (kappa = 0.90) and transmural grade (kappa = 0.79)
      between field strengths. Intra- and interobserver variability were low between
      both field strengths. Initial inversion time selected to null the signal of
      normal myocardium at 3.0 T was 57 msec +/- 20 longer than at 1.5 T (P < .01).
      CONCLUSION: By using the same turbo FLASH MR pulse sequence, there was strong
      agreement in mass and transmural extent of myocardial HE between 1.5 and 3.0 T.

PMID- 17209168
TI  - Circadian-dependent learning and memory enhancement in nociceptin receptor
      deficient mice with a novel KUROBOX apparatus using stress-free positive cue
      task.
AB  - Using the novel apparatus KUROBOX, learning and memory behaviors, as well as
      various parameters of movement activity, were reevaluated in mice deficient for
      nociceptin/orphanin FQ receptor (NOP-/- mice) or mu-opioid receptor (MOP-/-
      mice). This method has the advantages that no handling procedures are required
      throughout the experiments performed over 3 days, positive cue paradigms are used
      without water or shock stress, and the method does not disturb the nocturnal
      habit of mice. NOP-/- mice displayed a significant enhancement of learning and
      memory under stress-free conditions, but there were no changes in the various
      physical and psychological parameters of movement activity (nest stay ratio,
      distance moved, speed and angle in the movement) and biological rhythm that were
      measured. Enhancement of nocturnal learning was observed during the first 12-h
      dark cycle, and enhancement of memory was observed at the beginning of the second
      dark cycle in NOP-/- mice. In contrast, MOP-/- mice showed no significant change
      in learning and memory behaviors or in physical and psychological parameters of
      movement activity, except for speed, MOP-/- mice showed a significant decrease in
      speed of movement. Thus, the KUROBOX apparatus provides a useful alternative
      method to evaluate learning and memory activity under the more physiological
      conditions. In addition, this apparatus has an advantage that various physical
      and psychological parameters of movement activity affecting learning and memory
      behavior are also evaluated at the same time.

PMID- 17209169
TI  - The current and future search for obesity genes.

PMID- 17209170
TI  - Folic acid fortification: the good, the bad, and the puzzle of vitamin B-12.

PMID- 17209171
TI  - Risk assessment for vitamin D.
AB  - The objective of this review was to apply the risk assessment methodology used by
      the Food and Nutrition Board (FNB) to derive a revised safe Tolerable Upper
      Intake Level (UL) for vitamin D. New data continue to emerge regarding the health
      benefits of vitamin D beyond its role in bone. The intakes associated with those
      benefits suggest a need for levels of supplementation, food fortification, or
      both that are higher than current levels. A prevailing concern exists, however,
      regarding the potential for toxicity related to excessive vitamin D intakes. The
      UL established by the FNB for vitamin D (50 microg, or 2000 IU) is not based on
      current evidence and is viewed by many as being too restrictive, thus curtailing
      research, commercial development, and optimization of nutritional policy. Human
      clinical trial data published subsequent to the establishment of the FNB vitamin
      D UL published in 1997 support a significantly higher UL. We present a risk
      assessment based on relevant, well-designed human clinical trials of vitamin D.
      Collectively, the absence of toxicity in trials conducted in healthy adults that
      used vitamin D dose > or = 250 microg/d (10,000 IU vitamin D3) supports the
      confident selection of this value as the UL.

PMID- 17209172
TI  - Methyl balance and transmethylation fluxes in humans.
AB  - Various questions have been raised about labile methyl balance and total
      transmethylation fluxes, and further discussion has been encouraged. This report
      reviews and discusses some of the relevant evidence now available. The fact that,
      if needed, labile methyl balance is maintained by methylneogenesis appears to be
      established, but several aspects of transmethylation remain uncertain: definitive
      measurements of the rate of total transmethylation in humans of both sexes on
      various diets and at various ages; the extent to which synthesis of
      phosphatidylcholine has been underestimated; and the relative contributions of
      the 2 pathways for the formation of sarcosine (ie, N-methylglycine). The
      available evidence indicates that the quantitatively most important pathways for
      S-adenosylmethionine-dependent transmethylation in mammals are the syntheses of
      creatine by guanidinoacetate methyltransferase, of phosphatidylcholine by
      phosphatidylethanolamine methyltransferase, and of sarcosine by glycine N
      methyltransferase. Data presented in this report show that S-adenosylmethionine
      and methionine accumulate abnormally in the plasma of humans with glycine N
      methyltransferase deficiency but not of those with guanidinoacetate N
      methyltransferase deficiency or in the plasma or livers of mice devoid of
      phosphatidylethanolamine N-methyltransferase activity. The absence of such
      accumulations in the latter 2 conditions may be due to removal of S
      adenosylmethionine by synthesis of sarcosine. Steps that may help clarify the
      remaining issues include the determination of the relative rates of synthesis of
      sarcosine, creatine, and phosphatidylcholine by rapid measurement of the rates of
      radiolabel incorporation into these compounds from L-[methyl-3H]methionine
      administered intraportally to an experimental animal; clarification of the
      intracellular hepatic isotope enrichment value during stable-isotope infusion
      studies to enhance the certainty of methyl flux estimates during such studies;
      and definitive measurement of the dietary betaine intake from various diets.

PMID- 17209173
TI  - Adiponectin and adiponectin receptor gene variants in relation to resting
      metabolic rate, respiratory quotient, and adiposity-related phenotypes in the
      Quebec Family Study.
AB  - BACKGROUND: Despite adiponectin's presumed role in fatty acid oxidation and
      energy homeostasis, little is known about the effect of gene variants on
      substrate oxidation, energy expenditure, and adiposity-related phenotypes.
      OBJECTIVE: We examined the effects of genetic variation in adiponectin (ADIPOQ)
      and adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) on resting metabolic
      rate, respiratory quotient (RQ), and adiposity-related phenotypes. DESIGN: We
      studied the associations of ADIPOQ, ADIPOR1, and ADIPOR2 polymorphisms with
      resting metabolic rate, RQ, and body mass index, percentage body fat, sum of 6
      skinfold thicknesses, waist circumference, and total, subcutaneous, and visceral
      fat in 759 participants in the Quebec Family Study. RESULTS: The ADIPOQ 45T-->G
      single-nucleotide polymorphism (SNP) was significantly (P = 0.0002 to 0.04)
      associated with overall adiposity and abdominal adiposity; the rare homozygotes
      (G/G) had a leaner phenotype than did the carriers of the common allele. One SNP
      each in the putative promoter of ADIPOR1 (ie, -3882T-->C) and ADIPOR2 (ie, IVS1 
      1352G-->A) was associated with RQ (P = 0.03 and 0.04, respectively), and the
      association was even stronger in nonobese persons (P = 0.02 and 0.003). Carriers
      of the common alleles (ADIPOR1 T and ADIPOR2 G alleles) had a lower RQ than did
      the rare homozygotes. A significant genotype-by-genotype interaction (P = 0.0002
      to 0.02) was found between SNPs in the promoters of ADIPOQ (-3971A-->G) and
      ADIPOR1 (-3882T-->C). Subjects carrying the minor ADIPOQ allele (G allele) who
      were rare homozygotes (C/C) for the ADIPOR1 SNP had a higher RQ (P = 0.003) and
      greater overall (P < 0.03) and abdominal (P < 0.05) adiposity than did persons
      with other genotype combinations. CONCLUSIONS: Previous findings that the ADIPOQ
      45T-->G variant contributes to overall fatness and abdominal obesity are
      confirmed. Moreover, variants in the promoter region of both ADIPOR genes
      contribute to substrate oxidation.

PMID- 17209174
TI  - Waist circumference is associated with pulmonary function in normal-weight,
      overweight, and obese subjects.
AB  - BACKGROUND: Obesity is becoming a serious public health issue and is related to
      lung dysfunction. Because both weight and height are indicators of body size,
      body mass index (BMI) may not be an ideal index of obesity in prediction of
      pulmonary dysfunction. OBJECTIVE: The objective of the study was to determine the
      predictability of waist circumference (WC) and BMI for pulmonary function in
      adults with and without excess body weight. DESIGN: A cross-sectional study of
      1674 adults aged > or = 18 y was conducted in a rural community. Height, weight,
      WC, and pulmonary function were measured. Multivariate analysis was conducted.
      RESULTS: WC was negatively associated with forced vital capacity and forced
      expiratory volume in 1 s, and the associations were consistent across sex, age,
      and BMI categories. On average, a 1-cm increase in WC was associated with a 13-mL
      reduction in forced vital capacity and an 11-mL reduction in forced expiratory
      volume in 1 s. The association between WC and pulmonary function was consistent
      in subjects with normal weight, overweight, and obesity. In subjects with normal
      weight, BMI was positively associated with forced vital capacity and forced
      expiratory volume in 1 s. CONCLUSION: WC, but not BMI, is negatively and
      consistently associated with pulmonary function in normal-weight, overweight, and
      obese subjects.

PMID- 17209175
TI  - Normal-weight obese syndrome: early inflammation?
AB  - BACKGROUND: In obese subjects, the adipose mass represents an important source of
      proinflammatory cytokines. We have identified a new syndrome-the normal-weight
      obese (NWO) syndrome-in women with normal weight and body mass index but whose
      fat mass is >30% of their total body weight and whose risk of developing obesity
      related diseases is likely increased. OBJECTIVE: The aim of the present study was
      to verify the hypothesis that NWO women are characterized by early inflammation,
      related to body fat mass, and that their plasma proinflammatory cytokine
      concentrations are greater than those of nonobese women. DESIGN: Twenty NWO, 20
      preobese-obese, and 20 healthy (nonobese), age-matched white Italian women were
      studied. Anthropometric variables and plasma concentrations of proinflammatory
      cytokines and cardiovascular disease (CVD) risk factors were measured and
      compared between groups. RESULTS: Plasma values and body-composition measures
      were significantly different between the preobese-obese and nonobese women. No
      significant differences in body weight, laboratory values, or CVD risk factors
      were found between the NWO and nonobese groups. Compared with concentrations in
      the NWO women, plasma concentrations of interleukin (IL)-1alpha, IL-1beta, IL-6,
      IL-8, and TNF-alpha were significantly lower in the nonobese group and were
      significantly greater in the preobese-obese group. IL-6 and TNF-alpha
      concentrations were related to fat mass distribution in the NWO women.
      CONCLUSIONS: The proinflammatory cytokines could be regarded as significant
      prognostic indicators of the risk of obesity, CVD, and the metabolic syndrome in
      NWO women.

PMID- 17209176
TI  - Visceral abdominal fat is correlated with whole-body fat and physical activity
      among 8-y-old children at risk of obesity.
AB  - BACKGROUND: Abdominal fat is more related to health risk than is whole-body fat.
      Determining the factors related to children's visceral fat could result in
      interventions to improve child health. OBJECTIVE: Given the effects of physical
      activity on adults' visceral fat, it was hypothesized that, after accounting for
      whole-body fat, physical activity would be inversely related to children's
      visceral (VAT), but not to subcutaneous (SAT), abdominal adipose tissue. DESIGN:
      In this cross-sectional observational study conducted in forty-two 8-y-old
      children (21 boys, 21 girls) at risk of obesity [>75th body mass index (BMI)
      percentile, with at least one overweight parent], familial factors (eg, maternal
      BMI), historic weight-related factors (eg, birth weight), and the children's
      current physical activity (self-reported and measured with accelerometry) and
      diet were examined as potential correlates of the children's whole-body
      composition (measured with BMI and dual-energy X-ray absorptiometry) and
      abdominal fat distribution (measured by magnetic resonance imaging). RESULTS:
      Accelerometer-measured physical activity was related to whole-body fat (r = 
      0.32, P < 0.10), SAT (r = -0.29, P < 0.10), and VAT (r = -0.43, P < 0.05). In
      regression models, whole-body fat was positively associated with and the only
      significant correlate of SAT. Whole-body fat was positively related and
      accelerometer-measured physical activity was negatively and independently related
      to the children's VAT. CONCLUSIONS: Both SAT and VAT in 8-y-old children at risk
      of obesity are most closely associated with whole-body fat. However, after
      control for whole-body fat, greater physical activity is only associated with
      lower VAT, not SAT, in these children.

PMID- 17209177
TI  - Supplementation with calcium + vitamin D enhances the beneficial effect of weight
      loss on plasma lipid and lipoprotein concentrations.
AB  - BACKGROUND: Adequate calcium intake can have a favorable effect on some metabolic
      variables. OBJECTIVE: The objective of the study was to determine the effects of
      daily calcium intake and of supplementation with calcium and vitamin D
      (calcium+D) during a weight-loss intervention on blood pressures, plasma lipid
      and lipoprotein concentrations, and glucose and insulin concentrations in low
      calcium consumers. DESIGN: Healthy, overweight or obese women (n = 63) with a
      daily calcium intake of < 800 mg/d were randomly assigned in a double-blind
      manner to 1 of 2 groups: the group consuming 2 tablets/d of a calcium + vitamin D
      supplement (600 mg elemental calcium and 200 IU vitamin D/tablet) or the group
      consuming placebo; both groups observed a 700 kcal/d energy restriction. These 63
      women then completed a 15-wk weight-loss intervention. RESULTS: Initial daily
      calcium intake was significantly correlated with plasma HDL cholesterol (r =
      0.41, P < 0.001) and with 2-h postload glycemia (r = -0.29, P < 0.05) during an
      oral-glucose-tolerance test, independent of fat mass and waist circumference.
      After the 15-wk intervention, significantly greater decreases in total:LDL and
      LDL:HDL (P < 0.01 for both) and of LDL cholesterol (P < 0.05) were observed in
      the calcium+D group than in the placebo group. The differences in total:HDL and
      LDL:HDL were independent of changes in fat mass and in waist circumference. A
      tendency for more beneficial changes in HDL cholesterol, triacylglycerol, and
      total cholesterol was also observed in the calcium+D group (P = 0.08).
      CONCLUSION: Consumption of calcium+D during a weight-loss intervention enhanced
      the beneficial effect of body weight loss on the lipid and lipoprotein profile in
      overweight or obese women with usual low daily calcium intake.

PMID- 17209178
TI  - Postprandial monocyte activation in response to meals with high and low glycemic
      loads in overweight women.
AB  - BACKGROUND: Recent data show that atherosclerosis is initiated and perpetuated by
      inflammatory events. Activation of immune cells such as monocytes initiates
      inflammation, a key step in atherosclerosis. OBJECTIVE: We hypothesize that a
      high-glycemic load meal activates inflammatory cells, and that this is mediated
      by elevated circulating triacylglycerol-rich lipoproteins. DESIGN: Sixteen women
      [body mass index (in kg/m2): 25.7-29.6], aged 20-48 y, consumed meals with a high
      or a low glycemic load in a crossover fashion. Blood samples were collected
      before and up to 8 h after the meals. Samples were measured for glucose, insulin,
      triacylglycerols, and circulating cytokines, and expression of tumor necrosis
      factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) was measured by flow
      cytometry. RESULTS: At 3.5 h after the test meals, we observed a significant
      increase in monocytes expressing TNF-alpha with both high-and low-glycemic load
      meals. Also, expression of IL-1beta in monocytes tended to increase, but the
      change was not significant. The glycemic load of the meal did not influence
      circulating cytokines and had only a minimal effect on postprandial
      triacylglycerol concentrations despite marked postprandial changes in glycemia
      and circulating insulin concentrations. CONCLUSIONS: In the postprandial state,
      monocytes can be activated by both high-and low-glycemic load meals. The glycemic
      load of a single meal did not have a significant effect on the degree of
      activation of the monocytes in women who displayed only a modest increase in
      circulating triacylglycerols in response to test meals. Future studies should
      examine the effect of glycemic load in subjects who have a hyperlipemic response
      to dietary carbohydrate.

PMID- 17209179
TI  - Total body protein in healthy adolescent girls: validation of estimates derived
      from simpler measures with neutron activation analysis.
AB  - BACKGROUND: Little recent and accurate information about body protein content in
      healthy adolescent girls is available. OBJECTIVE: The objective was to assess the
      total body nitrogen (TBN) and total body protein (TBPr) contents of fat-free mass
      (P:FFM) in a group of healthy adolescent girls and to validate previously
      published TBN prediction equations. DESIGN: TBN was measured with in vivo neutron
      activation analysis (TBNNAA). Bone mineral density and FFM were measured with
      dual-energy X-ray absorptiometry (FFMDXA), total body water and FFM were measured
      with bioimpedance analysis, and FFM was assessed by measuring skinfold
      thicknesses in 51 girls with a mean (+/- SD) age of 14.7 +/- 0.7 y. The validity
      of the TBN prediction equations was assessed with Bland-Altman analysis. RESULTS:
      TBNNAA in our adolescent group was higher (1.49 kg) than values reported in
      earlier studies of women (1.25 and 1.31 kg), and P:FFM was slightly higher (23%)
      than that documented in adults (19-21%). Previously published TBN equations
      showed either systematic bias or wide limits of agreement. CONCLUSION: A
      predictive equation derived from the present study population based on FFMDXA
      improves the prediction of TBN for groups of young girls but may not be helpful
      for individuals in clinical settings.

PMID- 17209180
TI  - Validation study of energy expenditure and intake during calorie restriction
      using doubly labeled water and changes in body composition.
AB  - BACKGROUND: Clinical trials involving calorie restriction (CR) require an
      assessment of adherence to a prescribed CR with the use of an objective measure
      of energy intake (EI). OBJECTIVE: The objective was to validate the use of energy
      expenditure (EE) measured by doubly labeled water (DLW), in conjunction with
      precise measures of body composition, to calculate an individual's EI during 30%
      CR. DESIGN: Ten participants underwent 30% CR for 3 wk. During the last week (7
      d), 24-h EE was measured in a respiratory chamber and simultaneously by DLW
      (EEDLW). EI was calculated from 7-d EE measured by DLW and from changes in energy
      stores (ES) (weight and body composition). Calculated EI was then compared with
      the actual EI measured in the chamber by using the following equations:
      calculated EI (kcal/d) = EEDLW + DeltaES, where DeltaESFM/FFM (kcal/d) = (9.3 x
      DeltaFM, g/d) + (1.1 x DeltaFFM, g/d), FM is fat mass, and FFM is fat-free mass.
      RESULTS: We found close agreement (R = 0.88) between EE measured in the metabolic
      chamber and EEDLW during CR. Using the measured respiratory quotient, we found
      that the mean (+/-SD) EE(DLW) was 1934 +/- 377 kcal/d and EE measured in the
      metabolic chamber was 1906 +/- 327 kcal/d, ie, a 1.3 +/- 8.9% overestimation. EI
      calculated from EEDLW and from changes in ES was 8.7 +/- 36.7% higher than the
      actual EI provided during the chamber stay (1596 +/- 656 kcal/d). CONCLUSIONS:
      DLW methods can accurately estimate 24-h EE during CR. Although the mean
      difference between actual and calculated EIs for the group was small, we conclude
      that the interindividual variability was too large to provide an assessment of CR
      adherence on an individual basis.

PMID- 17209181
TI  - A whole-body model to distinguish excess fluid from the hydration of major body
      tissues.
AB  - BACKGROUND: Excess fluid (ExF) accumulates in the body in many conditions.
      Currently, there is no consensus regarding methods that adequately distinguish
      ExF from fat-free mass. OBJECTIVE: The aim was to develop a model to determine
      fixed hydration constants of primary body tissues enabling ExF to be calculated
      from whole-body measurements of weight, intracellular water (ICWWB), and
      extracellular water (ECWWB). DESIGN: Total body water (TBW) and ECWWB were
      determined in 104 healthy subjects by using deuterium and NaBr dilution
      techniques, respectively. Body fat was estimated by using a reference 4-component
      model, dual-energy X-ray absorptiometry, and air-displacement plethysmography.
      The model considered 3 compartments: normally hydrated lean tissue (NH_LT),
      normally hydrated adipose tissue (NH_AT), and ExF. Hydration fractions (HF) of
      NH_LT and NH_AT were obtained assuming zero ExF within the diverse healthy
      population studied. RESULTS: The HF of NH_LT mass was 0.703 +/- 0.009 with an ECW
      component of 0.266 +/- 0.007. The HF of NH_AT mass was 0.197 +/- 0.042 with an
      ECW component of 0.127 +/- 0.015. The ratio of ECW to ICW in NH_LT was 0.63
      compared with 1.88 in NH_AT. ExF can be estimated with a precision of 0.5 kg.
      CONCLUSIONS: To calculate ExF over a wide range of body compositions, it is
      important that the model takes into account the different ratios of ECW to ICW in
      NH_LT and NH_AT. This eliminates the need for adult age and sex inputs into the
      model presented. Quantification of ExF will be beneficial in the guidance of
      treatment strategies to control ExF in the clinical setting.

PMID- 17209182
TI  - Body-composition assessment in infancy: air-displacement plethysmography compared
      with a reference 4-compartment model.
AB  - BACKGROUND: A better understanding of the associations of early infant nutrition
      and growth with adult health requires accurate assessment of body composition in
      infancy. OBJECTIVE: This study evaluated the performance of an infant-sized air
      displacement plethysmograph (PEA POD Infant Body Composition System) for the
      measurement of body composition in infants. DESIGN: Healthy infants (n = 49; age:
      1.7-23.0 wk; weight: 2.7-7.1 kg) were examined with the PEA POD system. Reference
      values for percentage body fat (%BF) were obtained from a 4-compartment (4-C)
      body-composition model, which was based on measurements of total body water, bone
      mineral content, and total body potassium. RESULTS: Mean (+/- SD) reproducibility
      of %BF values obtained with the PEA POD system was 0.4 +/- 1.3%. Mean %BF
      obtained with the PEA POD system (16.9 +/- 6.5%) did not differ significantly
      from that obtained with the 4-C model (16.3 +/- 7.2%), and the regression between
      %BF for the 4-C model and that for the PEA POD system (R2 = 0.73, SEE = 3.7%BF)
      did not deviate significantly from the line of identity (y = x). CONCLUSIONS: The
      PEA POD system provided a reliable, accurate, and immediate assessment of %BF in
      infants. Because of its ease of use, good precision, minimum safety concerns, and
      bedside accessibility, the PEA POD system is highly suitable for monitoring
      changes in body composition during infant growth in both the research and
      clinical settings.

PMID- 17209183
TI  - Nutritional status in patients with diabetes and chronic kidney disease: a
      prospective study.
AB  - BACKGROUND: A poor nutritional status reduces the life expectancy of diabetes
      patients undergoing hemodialysis. OBJECTIVE: The study objective was to specify
      the nutritional outcome in patients with chronic kidney disease (CKD) and well
      controlled diabetes. DESIGN: Forty-five diabetes patients with CKD were enrolled
      in a cooperative-care program designed to control glucose, blood pressure, LDL
      cholesterol, and the albumin excretion rate (AER). Their glomerular filtration
      rate (GFR), body composition, serum albumin (SA), and resting energy expenditure
      were assessed and compared at baseline and 2 y later. RESULTS: Thirty-five
      patients did not start dialysis. Their glycated hemoglobin, blood pressure, LDL
      cholesterol, and AER improved; their GFR declined slowly (-3.3 mL x min(-1) x
      1.73 m(-2) x y(-1)). Their body mass index (BMI), lean body mass, and SA
      increased. The GFR decline was correlated negatively with the initial BMI (r = 
      0.37, P < 0.05) and positively with the initial GFR (r = 0.34, P < 0.05). Ten
      patients started hemodialysis: except for higher total body water (P < 0.05) and
      extracellular volume (P < 0.01), their initial nutritional status did not differ
      significantly from that of 10 patients with comparable baseline severe CKD but
      without dialysis. At the second evaluation, patients on hemodialysis lost lean
      body mass, and their SA was lower than that of the patients with severe CKD (P =
      0.05); lean body mass was unchanged and SA was higher (P = 0.01) in the patients
      with severe CKD. No significant difference was detected for resting energy
      expenditure. CONCLUSIONS: Nutritional status improved in CKD patients with well
      controlled diabetes without dialysis, and it deteriorated in patients who started
      dialysis. A high initial BMI was associated with a slower decline in GFR.

PMID- 17209184
TI  - FABP2 Ala54Thr genotype is associated with glucoregulatory function and lipid
      oxidation after a high-fat meal in sedentary nondiabetic men and women.
AB  - BACKGROUND: A common functional missense mutation [Ala54Thr of the fatty acid
      binding protein 2 gene (FABP2)] has previously been studied for associations with
      glucoregulation, postprandial lipemia, and lipid oxidation rates. However, most
      of those studies have not accounted for the interactive and potentially
      confounding effects of habitual physical activity and diet. OBJECTIVE: We tested
      the hypothesis that, in sedentary nondiabetic subjects following a low-fat diet,
      Thr54 FABP2 carriers have lower glucoregulatory function, greater postprandial
      lipemia, and greater lipid oxidation rates than do their Ala54 FABP2-homozygous
      counterparts. DESIGN: Men and women (n = 122) aged 50-75 y who were following a
      low-fat diet were genotyped and underwent oral-glucose-tolerance tests. A
      subgroup (n = 36) also underwent postprandial lipemia tests with lipid oxidation
      rate measurements. RESULTS: Thr54 carriers were less likely to have normal
      glucose tolerance (P = 0.05) and had higher fasting glucose concentrations (P =
      0.003) than did Ala54 homozygotes. In Thr54 carriers, the insulin sensitivity
      index was lower (P = 0.02), and the fasting insulin and the oral-glucose
      tolerance test insulin area under the curve were higher (P = 0.05 and 0.03,
      respectively) than in Ala54 homozygotes. FABP2 genotype was not associated with
      fasting or postprandial lipemia test triacylglycerol or free fatty acids (P > or
      = 0.22 for all), but postprandial lipid oxidation rates were higher (P = 0.01),
      which suggests that fat absorption is higher in Thr54 carriers than in Ala54
      homozygotes. CONCLUSIONS: In sedentary nondiabetic persons following a low-fat
      diet, FABP2 Thr54 carriers have lower glucose tolerance and lower insulin action
      than do Ala54-homozygous persons. Furthermore, FABP Thr54 carriers have higher
      lipid oxidation rates, which may be the mechanism of glucoregulatory dysfunction.

PMID- 17209185
TI  - Exercise increases the proportion of fat utilization during short-term
      consumption of a high-fat diet.
AB  - BACKGROUND: Increases in energy substrate oxidation occur at different rates
      after an increase in either fat or carbohydrate intake. Adaptations to increased
      fat intake are relatively slow and are influenced by activity level. OBJECTIVE:
      We tested the hypothesis that increased levels of daily activity, as influenced
      by added exercise, would have a graded effect on the rate of compensatory
      adjustment to a short-term high-fat diet. DESIGN: Daily total energy expenditure
      and macronutrient oxidation were measured at 3 physical activity levels (PALs) by
      using a whole-room indirect calorimeter in 10 adult women as they transitioned
      from a 1-d low-fat (30% of energy) control diet to a 4-d high-fat (50% of energy)
      diet. The 3 PALs (1.4, 1.6, and 1.8) were provided daily by increases in bicycle
      ergometer exercise time. RESULTS: An increase in physical activity led to a
      greater increase in the nonprotein respiratory exchange ratio (-0.047 +/- 0.02, 
      0.064 +/- 0.02, and -0.071 +/- 0.02; P < 0.0001) and 24-h fat oxidation (113 +/-
      24, 125 +/- 19, and 147 +/- 20 g/d; P < 0.0001) for PALs of 1.4, 1.6, and 1.8,
      respectively, after the transition from the low-fat control diet to the high-fat
      diet. Random-effects analysis found a significant (P = 0.003) relation between
      PAL and the compensatory fat oxidation response to a high-fat diet. CONCLUSIONS:
      Amounts of exercise consistent with the Institute of Medicine's recommendations
      reduce the time required to match fat oxidation to a change in the percentage of
      fat in the diet. Because short-term consumption of high-fat diets is thought to
      contribute to excess fat accumulation, regular exercise should be protective and
      should help maintain a healthy body composition.

PMID- 17209186
TI  - Plasma B vitamins and their relation to the severity of chronic heart failure.
AB  - BACKGROUND: Total homocysteine (tHcy) has been linked to the severity of chronic
      heart failure (CHF). Elevated tHcy concentrations are mainly caused by folate and
      vitamin B-12 deficiencies. OBJECTIVE: We hypothesized that folate and vitamin B
      12 deficiencies can explain the relation between tHcy and the severity of CHF.
      DESIGN: We investigated 987 CHF patients. All subjects underwent a physical
      examination and blood sampling. Cardiac catheterization was performed in 929
      patients and echocardiography in 460 patients. Serum tHcy, folate, vitamin B-12,
      and N-terminal pro-B-type natriuretic-peptide (NT-proBNP) were measured and renal
      and hepatic function were studied. RESULTS: tHcy increased with increasing New
      York Heart Association (NYHA) classes of heart failure (P < 0.001) and correlated
      with the left ventricular ejection fraction (EF; r = -0.150, P < 0.001). Contrary
      to the hypothesis, vitamin B-12 (P < 0.001) increased with NYHA class (P < 0.001)
      and was negatively correlated with EF (r = -0.080, P = 0.015). Folate showed no
      relation with NYHA class or EF. Comparable results were obtained for NT-proBNP
      (tHcy: r = 0.27, P < 0.001; vitamin B-12: r = 0.091, P = 0.004; folate: r = 
      0.045, P = 0.169). The correlations between tHcy, EF, and NT-proBNP were
      significantly stronger in patients without coronary artery disease (CAD) than in
      those with CAD. Regression analysis showed that tHcy, but not B vitamins, is a
      strong predictor of EF and NT-proBNP. CONCLUSIONS: This study showed that tHcy,
      but not folate and vitamin B-12, is related to clinical, echocardiographic, and
      laboratory variables of CHF, which indicates a relation between tHcy and the
      severity of CHF. This relation is stronger in patients without CAD. The lack of
      association of folate and the paradoxical relation of vitamin B-12 with CHF can
      possibly be explained by a disturbance in hepatic homeostasis.

PMID- 17209187
TI  - A prospective analysis of plasma 25-hydroxyvitamin D concentrations in white and
      black prepubertal females in the southeastern United States.
AB  - BACKGROUND: Little is known regarding changes in vitamin D status among children
      living in the southern United States and whether these changes are race
      dependent. OBJECTIVES: The aims were to prospectively assess plasma 25
      hydroxyvitamin D [25(OH)D] concentrations in prepubertal black and white girls (n
      = 83) living in northeast Georgia and to determine whether 25(OH)D concentrations
      change with increasing age. DESIGN: Plasma samples were obtained annually over a
      time frame of 1-7 y, and 25(OH)D concentrations were assessed by using
      radioimmunoassay. Percentage body fat (%BF) and fat-free soft tissue (FFST) mass
      were measured by using dual-energy X-ray absorptiometry. Linear mixed-effects
      models were used with height, weight, body mass index percentile, %BF, FFST,
      pubertal stage, dietary intake, physical activity, and socioeconomic status as
      covariates. RESULTS: Plasma 25(OH)D values < 80 nmol/L were observed in 75% of
      the participants. Plasma 25(OH)D values (analyzed on the natural logarithm scale)
      decreased with increasing age (P = 0.02), independent of race. Plasma 25(OH)D
      values were higher in whites than in blacks (P < 0.0001), and the amount of this
      difference depended on season (P < 0.001 for all seasons). A significant negative
      association between FFST and 25(OH)D, beyond the effects of age, race, and season
      (P = 0.007), was observed. The effects of age, race, and season on 25(OH)D
      remained significant when dietary calcium, vitamin D, and physical activity were
      used as covariates; however, after adjustment for FFST, only the effects of race
      and season remained. CONCLUSIONS: White girls living in the southeastern United
      States have higher 25(OH)D concentrations than do black girls, and the magnitude
      of this difference depends on the season. Decreases in 25(OH)D with age are
      associated with increases in FFST. Whether FFST requires additional vitamin D
      during growth remains to be determined.

PMID- 17209188
TI  - Effect of high-dose iron supplements on fractional zinc absorption and status in
      pregnant women.
AB  - BACKGROUND: Women have an increased risk of iron deficiency during pregnancy
      because of the demands of the developing fetus. Iron supplements are commonly
      advocated as a prophylactic treatment and are generally taken with meals to
      reduce side effects, but iron can interfere with the absorption of zinc.
      OBJECTIVE: The aim was to determine the effect of consuming an iron supplement
      (100 mg Fe/d as ferrous gluconate) with meals from 16 wk gestation to term on
      zinc status and absorption. DESIGN: Stable-isotope techniques were used to
      measure zinc status (exchangeable zinc pool, EZP) and fractional zinc absorption
      (FZA) in early and late pregnancy from a meal consumed at a different time from
      that of iron supplement or placebo consumption in 6 women given iron supplements
      and 7 given a placebo. RESULTS: FZA increased during pregnancy, independent of
      iron supplementation. FZA was significantly higher (P < 0.001) at week 34 than at
      weeks 16 and 24, and urinary zinc excretion was higher at week 34 than at week 16
      (P = 0.02). The size of the EZP remained unchanged throughout pregnancy and was
      unaffected by iron supplementation. The iron status of iron-supplemented women
      was higher than that of the placebo group. CONCLUSIONS: In iron-replete pregnant
      women who consumed a Western diet, no detectable adverse effects on zinc
      metabolism were observed after ingestion of 100 mg Fe/d. An increase in the
      efficiency of zinc absorption was observed during late pregnancy.

PMID- 17209189
TI  - Efficacy of daily and weekly multiple micronutrient food-like tablets for the
      correction of iodine deficiency in Indonesian males aged 6-12 mo.
AB  - BACKGROUND: Infants are highly vulnerable to iodine deficiency, and little data
      exist on the effect of multiple micronutrient supplementation on their iodine
      status. OBJECTIVE: We aimed to compare the efficacy of daily and weekly multiple
      micronutrient food-like tablets (foodLETs) on increasing iodine status among
      infants. DESIGN: In a double-blind, placebo-controlled trial, 133 Indonesian
      males aged 6-12 mo were randomly assigned to 1 of 4 groups: a daily multiple
      micronutrient foodLET providing the Recommended Nutrient Intake (RNI)(DMM), a
      weekly multiple-micronutrient foodLET providing twice the RNI (WMM), a daily 10
      mg Fe foodLET (DI), or placebo. Urinary iodine (UI) concentrations were measured
      at baseline and at 23 wk. RESULTS: At baseline, the average UI concentration
      (1.37 micromol/L) was within the normal range, and 30.8% of subjects had iodine
      deficiency (UI < 0.79 micromol/L). At 23 wk, the DMM group had the highest
      increment in UI; however, after adjustment for initial UI, the changes in UI were
      not significantly different between the 4 groups (P = 0.39). Initial UI
      correlated inversely with the changes in UI (P < 0.001). The DMM group had the
      greatest reduction and increment in the proportion of iodine-deficient infants
      and in infants with iodine excess, respectively; however, no significant
      difference was found in these proportions (P = 0.13 and P = 0.42) between the 4
      groups. CONCLUSION: Daily consumption of a multiple-micronutrient foodLET
      providing the RNI during infancy may be one strategy to improve iodine status.

PMID- 17209190
TI  - Evaluation of formulas for calculating total energy requirements of preadolescent
      children with cystic fibrosis.
AB  - BACKGROUND: To support age-appropriate growth and to prevent and treat
      malnutrition in children with cystic fibrosis (CF), energy requirements for those
      children are often set above the requirements for healthy children. Care
      providers use one of several empirically derived formulas to calculate energy
      requirements, yet the validity of these formulas has seldom been tested.
      OBJECTIVE: We evaluated 6 proposed formulas for calculating energy requirements
      in children with CF against a total energy requirement for children with CF (TER
      CF) derived from measured total energy expenditure, fecal fat energy loss, and
      the theoretic energy required for age-appropriate tissue accretion. DESIGN:
      Subjects were children aged 6-8 y who had CF and pancreatic insufficiency.
      Calculated TERs from each formula were evaluated against TER-CF by using summary
      statistics, regression analysis, and residual plots. RESULTS: Subjects (n = 53)
      had suboptimal nutrition and growth status and mild-to-moderate lung disease. The
      formula that most closely (within 2%) approximated TER-CF was the estimated
      energy requirement (EER) formula at the active level (EERact). Regression
      analysis of TER-CF onto calculated TER from each formula yielded the best indexes
      of model fit for the EERact formula; residual plots of the EERact formula were
      tightly and normally distributed around zero. CONCLUSIONS: The EERact formula
      should be used to establish TER-CF in children in this age group who have mild-to
      moderate CF. Changes in weight, height, and other indicators of nutritional
      status must be monitored to modify TER-CF as needed to support individual patient
      care goals.

PMID- 17209191
TI  - Infant nutrition and stereoacuity at age 4-6 y.
AB  - BACKGROUND: Breastfeeding has been reported to benefit visual development in
      children. A higher concentration of docosahexaneoic acid (DHA) in breast milk
      than in formula has been proposed as one explanation for this association and as
      a rationale for adding DHA to infant formula, but few long-term data support this
      possibility. OBJECTIVE: The objectives of the study were, first, to test the
      hypothesis that breastfeeding benefits stereoscopic visual maturation and,
      second, if that benefit is shown, to ascertain whether it is mediated by the
      dietary intake of DHA. DESIGN: Stereoacuity was measured by using the random dot
      E test (primary outcome), and visual acuity was measured by using the Sonksen
      Silver acuity system (secondary outcome) in previously breastfed (n = 78) or
      formula-fed (n = 184) children aged 4-6 y who had been followed prospectively
      from birth. In the formula-fed group, children were randomly assigned to receive
      formula with either DHA or arachidonic acid (n = 94) or a control formula (n =
      90) for the first 6 mo. RESULTS: Breastfed children had a significantly (P =
      0.001) greater likelihood of foveal stereoacuity (high-grade or < 100 s/arc) than
      did formula-fed children (odds ratio: 2.5; 95% CI: 1.4, 4.5) independent of
      potential confounding (P = 0.005). Stereoacuity did not differ significantly
      between children randomly assigned to DHA-supplemented or control formula. None
      of the groups differed in Sonksen-Silver visual acuity. CONCLUSIONS: These
      findings support the hypothesis that breastfeeding benefits long-term
      stereoscopic development. An effect of DHA cannot be excluded, but the lack of
      difference in stereoacuity between infants randomly assigned to DHA-containing
      and those assigned to control formula raises the hypothesis that factors in
      breast milk other than DHA account for the observed benefits.

PMID- 17209192
TI  - A prospective, double-blind, placebo-controlled trial to establish a safe gluten
      threshold for patients with celiac disease.
AB  - BACKGROUND: Treatment of celiac disease (CD) is based on the avoidance of gluten
      containing food. However, it is not known whether trace amounts of gluten are
      harmful to treated patients. OBJECTIVE: The objective was to establish the safety
      threshold of prolonged exposure to trace amounts of gluten (ie, contaminating
      gluten). DESIGN: This was a multicenter, double-blind, placebo-controlled,
      randomized trial in 49 adults with biopsy-proven CD who were being treated with a
      gluten-free diet (GFD) for > or =2 y. The background daily gluten intake was
      maintained at < 5 mg. After a baseline evaluation (t0), patients were assigned to
      ingest daily for 90 d a capsule containing 0, 10, or 50 mg gluten. Clinical,
      serologic, and histologic evaluations of the small intestine were performed at t0
      and after the gluten microchallenge (t1). RESULTS: At t0, the median villous
      height/crypt depth (Vh/Cd) in the small-intestinal mucosa was significantly lower
      and the intraepithelial lymphocyte (IEL) count (x 100 enterocytes) significantly
      higher in the CD patients (Vh/Cd: 2.20; 95% CI: 2.11, 2.89; IEL: 27; 95% CI: 23,
      34) than in 20 non-CD control subjects (Vh/Cd: 2.87; 95% CI: 2.50, 3.09; IEL: 22;
      95% CI: 18, 24). One patient (challenged with 10 mg gluten) developed a clinical
      relapse. At t(1), the percentage change in Vh/Cd was 9% (95% CI: 3%, 15%) in the
      placebo group (n = 13), -1% (-18%, 68%) in the 10-mg group (n = 13), and -20% (
      22%, -13%) in the 50-mg group (n = 13). No significant differences in the IEL
      count were found between the 3 groups. CONCLUSIONS: The ingestion of
      contaminating gluten should be kept lower than 50 mg/d in the treatment of CD.

PMID- 17209193
TI  - Interorgan amino acid exchange in humans: consequences for arginine and
      citrulline metabolism.
AB  - BACKGROUND: The liver plays a central role in amino acid metabolism. However,
      because of limited accessibility of the portal vein, human data on this subject
      are scarce. OBJECTIVE: We studied hepatic amino acid metabolism in noncirrhotic
      fasting patients undergoing liver surgery. DESIGN: Twenty patients undergoing
      hepatectomy for colorectal metastases in a normal liver were studied. Before
      resection, blood was sampled from a radial artery, portal vein, hepatic vein, and
      renal vein. Organ blood flow was measured by duplex ultrasound scan. RESULTS: The
      intestine consumed glutamine and released citrulline. Citrulline was taken up by
      the kidney. This was accompanied by renal arginine release, which supports the
      view that glutamine is a precursor for arginine synthesis through an intestinal
      renal pathway. The liver was found to extract citrulline from this pathway at a
      rate that was dependent on intestinal citrulline release (P < 0.0001) and hepatic
      citrulline influx (P = 0.03). Fractional hepatic extractions of citrulline (8.4%)
      and arginine (11.5%) were not significantly different. Eighty-eight percent of
      arginine reaching the liver passed it unchanged. Splanchnic citrulline release
      could account for one-third of renal citrulline uptake. CONCLUSIONS: This is the
      first study of hepatic and interorgan amino acid metabolism in humans with a
      normal liver. The data indicate that glutamine is a precursor of ornithine, which
      can be converted to citrulline by the intestine; citrulline is transformed in the
      kidneys to arginine. Hepatic citrulline uptake limits the amount of gut-derived
      citrulline reaching the kidney. These findings may have implications for
      interventions aimed at increasing systemic arginine concentrations.

PMID- 17209194
TI  - Glutathione, glutathione peroxidase, and selenium status in HIV-positive and HIV
      negative adolescents and young adults.
AB  - BACKGROUND: Antioxidant nutrient deficiencies may hasten the progression of HIV
      disease by impairing antioxidant defenses. OBJECTIVE: The objective of the study
      was to determine whether HIV infection is associated with poor selenium status
      and low antioxidant protection by glutathione and glutathione peroxidase (GPX).
      DESIGN: In a cross-sectional study of 365 HIV-positive and HIV-negative
      adolescents and young adults, we examined the relation of plasma selenium, whole
      blood glutathione, and whole-blood GPX to HIV status, disease severity, immune
      activation, and oxidative damage. RESULTS: Selenium deficiency (plasma selenium <
      0.070 microg/mL) was not seen in any subjects, and plasma selenium in 244 HIV
      positive subjects (0.120 +/- 0.0013 microg/mL) did not differ significantly (P =
      0.071) from that in 121 HIV-negative subjects (0.125 +/- 0.0020 microg/mL) .
      However, multiple regression analysis after adjustment for covariates showed a
      significant (P = 0.002) negative association between HIV-associated immune
      activation (plasma neopterin) and plasma selenium concentrations. GPX activity
      was highest in HIV-positive subjects taking antiretroviral therapy (median: 14.2;
      25th, 75th percentiles: 11.1, 18.7 U/mL; n = 130), intermediate in HIV-positive
      subjects not taking antiretroviral therapy (11.8; 9.4, 15.1 U/mL; n = 114), and
      lowest in HIV-negative subjects (10.6; 8.6, 12.7 U/mL; n = 121; P < 0.05 for all
      comparisons). GPX was also positively associated with malondialdehyde, a marker
      of oxidative damage. CONCLUSIONS: Subjects had adequate selenium status, although
      HIV-related immune activation was associated with lower plasma selenium
      concentrations. GPX activity appears to have been induced by the oxidative stress
      associated with HIV infection and use of antiretroviral therapy. Thus, young,
      well-nourished subjects can mount a compensatory antioxidant response to HIV
      infection.

PMID- 17209195
TI  - Micronutrient status during lactation in HIV-infected and HIV-uninfected South
      African women during the first 6 mo after delivery.
AB  - BACKGROUND: Little information on the micronutrient status of HIV-infected (HIV
      positive) breastfeeding women is available. OBJECTIVE: The objective was to
      compare the protein and micronutrient status of South African breastfeeding women
      by HIV status. DESIGN: Serum albumin, prealbumin, vitamin B-12, folate, retinol,
      alpha-tocopherol, hemoglobin, ferritin, and zinc concentrations were compared
      between 92 HIV-positive and 52 HIV-uninfected (HIV-negative) mothers 6, 14, and
      24 wk after delivery. C-reactive protein and alpha1-acid glycoprotein were used
      as proxy indicators of an inflammatory process. RESULTS: Mean albumin and
      prealbumin were significantly lower in HIV-positive mothers, and a higher
      proportion of HIV-positive mothers had low albumin concentrations (< 35 g/L).
      Less than 45% of the mothers were vitamin B-12 or folate sufficient.
      Significantly more HIV-positive (70.5%) than HIV-negative (46.2%) mothers had
      marginal vitamin B-12 status (P < 0.05), and mean folate concentrations were
      lower in HIV-positive mothers (P = 0.05). Mean serum retinol was significantly
      lower in HIV-positive mothers, even after control for the acute phase response.
      At 24 wk, 70% of both groups had an alpha-tocopherol deficiency (< 11.6
      micromol/L), but no significant difference by HIV status was observed. More HIV
      positive (33.3%) than HIV-negative (8.7%) mothers had anemia (P = 0.018), whereas
      25% of all mothers had low serum ferritin concentrations. After the acute phase
      response was controlled for, zinc deficiency was more common in HIV-positive
      (45.0%) than in HIV-negative (25.0%) mothers (P = 0.05). CONCLUSIONS:
      Deficiencies in vitamins B-12, folate, alpha-tocopherol, ferritin, and zinc are
      common in South African breastfeeding mothers. HIV-positive mothers had lower
      mean serum concentrations of albumin, prealbumin, folate, retinol, and hemoglobin
      than did HIV-negative mothers.

PMID- 17209196
TI  - Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive
      impairment in older Americans in the age of folic acid fortification.
AB  - BACKGROUND: Historic reports on the treatment of pernicious anemia with folic
      acid suggest that high-level folic acid fortification delays the diagnosis of or
      exacerbates the effects of vitamin B-12 deficiency, which affects many seniors.
      This idea is controversial, however, because observational data are few and
      inconclusive. Furthermore, experimental investigation is unethical. OBJECTIVE: We
      examined the relations between serum folate and vitamin B-12 status relative to
      anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score <
      34) in senior participants in the 1999-2002 US National Health and Nutrition
      Examination Survey. DESIGN: The subjects had normal serum creatinine
      concentrations and reported no history of stroke, alcoholism, recent anemia
      therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We
      defined low vitamin B-12 status as a serum vitamin B-12 concentration < 148
      pmol/L or a serum methylmalonic acid concentration > 210 nmol/L-the maximum of
      the reference range for serum vitamin B-12-replete participants with normal
      creatinine. RESULTS: After control for demographic characteristics, cancer,
      smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal
      vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI:
      1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment
      (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum
      folate > 59 nmol/L (80th percentile), as opposed to < or = 59 nmol/L, was
      associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR:
      2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high
      versus normal serum folate to these outcomes were < 1.0 (P(interaction) < 0.05),
      but significantly < 1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9).
      CONCLUSION: In seniors with low vitamin B-12 status, high serum folate was
      associated with anemia and cognitive impairment. When vitamin B-12 status was
      normal, however, high serum folate was associated with protection against
      cognitive impairment.

PMID- 17209197
TI  - Differential associations of fast food and restaurant food consumption with 3-y
      change in body mass index: the Coronary Artery Risk Development in Young Adults
      Study.
AB  - BACKGROUND: Away-from-home food consumption has rapidly increased, though little
      is known about the independent associations of restaurant food and fast food
      intake with body mass index (BMI) and BMI change. OBJECTIVE: The aim was to
      compare the associations of restaurant food and fast food consumption with
      current and 3-y changes in BMI. DESIGN: Multivariate linear regression models,
      with control for demographic and lifestyle factors, were used to examine cross
      sectional and longitudinal associations of away-from-home eating with BMI by
      using data from subjects of the Coronary Artery Risk Development in Young Adults
      Study (n = 3394) obtained at exam years 7 (1992-1993) and 10 (1995-1996).
      RESULTS: Forty percent of the sample increased their weekly consumption of
      restaurant or fast food, though mean (+/-SD) changes were -0.16 +/- 2.39 times/wk
      (P = 0.0001) and -0.56 +/- 3.04 times/wk (P < 0.0001), respectively. Cross
      sectionally, fast food, but not restaurant food, consumption was positively
      associated with BMI. Similarly, higher consumption of fast food at year 7 was
      associated with a 0.16-unit higher BMI at year 10. After adjustment for baseline
      away-from-home eating, increased consumption of fast food only (beta: 0.20; 95%
      CI: 0.01, 0.39) and of both restaurant food and fast food (beta: 0.29; 95% CI:
      0.06, 0.51) were positively associated with BMI change, though the estimates were
      not significantly different (P = 0.47). Increased consumption of restaurant food
      only was unrelated to BMI change (beta: -0.01; 95% CI: -0.21, 0.19), which
      differed significantly (P = 0.014) from the estimate for an increase in both
      restaurant food and fast food intake. CONCLUSIONS: We found differential effects
      of restaurant food and fast food intakes on BMI, although the observed
      differences were not always statistically significant. More research is needed to
      determine whether the differential effects are related to consumer
      characteristics or the food itself.

PMID- 17209199
TI  - Low and deficient niacin status and pellagra are endemic in postwar Angola.
AB  - BACKGROUND: Outbreaks of pellagra were documented during the civil war in Angola,
      but no contemporary data on the incidence of pellagra or the prevalence of niacin
      deficiency were available. OBJECTIVE: The objective was to investigate the
      incidence of pellagra and the prevalence of niacin deficiency in postwar Angola
      and their relation with dietary intake, poverty, and anthropometric status.
      DESIGN: Admissions data from 1999 to 2004 from the pellagra treatment clinic in
      Kuito, Angola, were analyzed. New patients admitted over 1 wk were examined, and
      urine and blood samples were collected. A multistage cluster population survey
      collected data on anthropometric measures, household dietary intakes,
      socioeconomic status, and clinical signs of pellagra for women and children.
      Urinary excretion of 1-methylnicotinamide, 1-methyl-2-pyridone-5-carboxymide, and
      creatinine was measured and hemoglobin concentrations were measured with a
      portable photometer. RESULTS: The incidence of clinical pellagra has not
      decreased since the end of the civil war in 2002. Low excretion of niacin
      metabolites was confirmed in 10 of 11 new clinic patients. Survey data were
      collected for 723 women aged 15-49 y and for 690 children aged 6-59 mo. Excretion
      of niacin metabolites was low in 29.4% of the women and 6.0% of the children, and
      the creatinine-adjusted concentrations were significantly lower in the women than
      in the children (P < 0.001, t test). In children, niacin status was positively
      correlated with the household consumption of peanuts (r = 0.374, P = 0.001) and
      eggs (r = 0.290, P = 0.012) but negatively correlated with socioeconomic status
      (r = -0.228, P = 0.037). CONCLUSIONS: The expected decrease in pellagra incidence
      after the end of the civil war has not occurred. The identification of niacin
      deficiency as a public health problem should refocus attention on this
      nutritional deficiency in Angola and other areas of Africa where maize is the
      staple.

PMID- 17209198
TI  - Serum selenium and risk of prostate cancer-a nested case-control study.
AB  - BACKGROUND: Selenium is a potential chemopreventive agent against prostate
      cancer, whose chemoprotective effects are possibly mediated through the
      antioxidative properties of selenoenzymes. Interrelations with other
      antioxidative agents and oxidative stressors, such as smoking, are poorly
      understood. OBJECTIVES: The aims were to investigate the association between
      serum selenium and prostate cancer risk and to examine interactions with other
      antioxidants and tobacco use. DESIGN: A nested case-control study was performed
      within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer
      Screening Trial. Serum selenium in prospectively collected samples was compared
      between 724 incident prostate cancer case subjects and 879 control subjects,
      frequency-matched for age, time since initial screen, and year of blood draw. The
      men were followed for up to 8 y. RESULTS: Overall, serum selenium was not
      associated with prostate cancer risk (P for trend = 0.70); however, higher serum
      selenium was associated with lower risks in men reporting a high (more than the
      median: 28.0 IU/d) vitamin E intake [odds ratio (OR) for the highest compared
      with the lowest quartile of selenium: 0.58; 95% CI: 0.37, 0.91; P for trend =
      0.05; P for interaction = 0.01] and in multivitamin users (OR for highest
      compared with the lowest quartile of selenium: 0.61; 95% CI: 0.36, 1.04; P for
      trend = 0.06; P for interaction = 0.05). Furthermore, among smokers, high serum
      selenium concentrations were related to reduced prostate cancer risk (OR for the
      highest compared with the lowest quartile of selenium: 0.65; 95% CI: 0.44, 0.97;
      P for trend = 0.09; P for interaction = 0.007). CONCLUSION: Greater prediagnostic
      serum selenium concentrations were not associated with prostate cancer risk in
      this large cohort, although greater concentrations were associated with reduced
      prostate cancer risks in men who reported a high intake of vitamin E, in
      multivitamin users, and in smokers.

PMID- 17209200
TI  - Carbohydrate intake and HDL in a multiethnic population.
AB  - BACKGROUND: Ethnic differences in serum lipids are not explained by genetics,
      central adiposity, lifestyle, or diet, possibly because dietary carbohydrate has
      not been considered. OBJECTIVE: The aim was to evaluate the relation between
      carbohydrate intake and HDL and triacylglycerol concentrations in a multiethnic
      population. DESIGN: We conducted a population-based cross-sectional study of 619
      Canadians of Aboriginal, South Asian, Chinese, and European origin with no
      previously diagnosed medical conditions. Energy-adjusted carbohydrate intake was
      measured by a validated food-frequency questionnaire. RESULTS: South Asians
      consumed the most carbohydrate, followed by European, Aboriginal, and Chinese
      persons. Mean (95% CI) HDL concentrations in the lowest and highest categories of
      carbohydrate intake after adjustment for age, sex, ethnicity, physical activity,
      smoking, the waist-to-hip ratio, body mass index, alcohol intake, and intakes of
      total energy, protein, and fiber were 1.21 mmol/L (1.16, 1.27 mmol/L) and 1.08
      mmol/L (1.02, 1.13 mmol/L), respectively, and HDL cholesterol was significantly
      (P < 0.01) higher in the lowest tertile of carbohydrate intake than in the
      highest tertile. High carbohydrate intake was associated with higher fasting
      triacylglycerols (P = 0.04); the adjusted mean fasting triacylglycerol
      concentrations in the lowest and highest categories of carbohydrate intake were
      1.43 mmol/L (1.28, 1.60 mmol/L) and 1.71 mmol/L (1.57, 1.87 mmol/L),
      respectively. Fewer servings of sugar-containing soft drinks, juices, and snacks
      were associated with higher HDL (P for trend = 0.02); the multivariate-adjusted
      mean HDL in the lowest and highest categories of carbohydrate intake was 1.22
      mmol/L (1.17, 1.27 mmol/L) and 1.11 mmol/L (1.06, 1.26 mmol/L), respectively.
      CONCLUSIONS: Differences in HDL and triacylglycerols observed in different ethnic
      groups may be due in part to carbohydrate intake. Reducing the frequency of
      intake of sugar-containing soft drinks, juices, and snacks may be beneficial.

PMID- 17209201
TI  - Dietary fatty acid intakes and the risk of ovulatory infertility.
AB  - BACKGROUND: Pharmacologic activation of the peroxisome proliferator-activated
      receptor gamma (PPAR-gamma) improves ovulatory function in women with polycystic
      ovary syndrome, and specific dietary fatty acids can affect PPAR-gamma activity.
      OBJECTIVE: The objective of the study was to assess whether the intakes of total
      fat, cholesterol, and major types of fatty acids affect the risk of ovulatory
      infertility. DESIGN: We conducted a prospective cohort study of 18 555 married,
      premenopausal women without a history of infertility who attempted a pregnancy or
      became pregnant between 1991 and 1999. Diet was assessed twice during follow-up
      by using a food-frequency questionnaire. RESULTS: During follow-up, 438 incidents
      of ovulatory infertility were reported. In logistic regression analyses, intakes
      of total fat, cholesterol, and most types of fatty acids were not related to
      ovulatory infertility. Each 2% increase in the intake of energy from trans
      unsaturated fats, as opposed to that from carbohydrates, was associated with a
      73% greater risk of ovulatory infertility after adjustment for known and
      suspected risk factors for this condition [relative risk (RR) = 1.73; 95% CI:
      1.09, 2.73]. Obtaining 2% of energy intake from trans fats rather than from n-6
      polyunsaturated fats was associated with a similar increase in the risk of
      ovulatory infertility (RR = 1.79; 95% CI: 1.11, 2.89). In addition, obtaining 2%
      of energy from trans fats rather than from monounsaturated fats was associated
      with a more than doubled risk of ovulatory infertility (RR = 2.31; 95% CI: 1.09,
      4.87). CONCLUSION: trans Unsaturated fats may increase the risk of ovulatory
      infertility when consumed instead of carbohydrates or unsaturated fats commonly
      found in nonhydrogenated vegetable oils.

PMID- 17209202
TI  - Benefits of ketogenic diets.

PMID- 17209203
TI  - Individual variation in the metabolic syndrome: a new perspective on the debate.

PMID- 17209204
TI  - Severe pneumonia research and the problem of case definition: the example of zinc
      trials.

PMID- 17209205
TI  - NIH State-of-the-Science Conference: Multivitamin/Mineral Supplements and Chronic
      Disease Prevention, May 15-17, 2006, Bethesda, Maryland, USA.

PMID- 17209206
TI  - National Institutes of Health State-of-the-Science Conference Statement:
      multivitamin/mineral supplements and chronic disease prevention.

PMID- 17209207
TI  - Multivitamin/Mineral supplements and prevention of chronic disease: executive
      summary.

PMID- 17209208
TI  - Multivitamin and multimineral dietary supplements: definitions, characterization,
      bioavailability, and drug interactions.
AB  - Although multivitamins, multiminerals, and similar terms (eg, multis or
      multiples) are commonly used, they have no standard scientific, regulatory, or
      marketplace definitions. Thus, multivitamins-multiminerals refers to products
      with widely varied compositions and characteristics. Multivitamin-multimineral
      composition databases use label values as surrogates for analyzed values.
      However, actual vitamin and mineral amounts often deviate from label values.
      Vitamin and mineral bioavailability for dietary supplements also lacks a standard
      scientific and regulatory definition and validated in vitro and animal models
      that accurately reflect human bioavailabilities. Systematic information on the
      bioavailability and bioequivalence of vitamins and minerals in marketed products
      and on potential drug interactions is scarce. Because of limited information on
      product characteristics, our ability to directly compare results across studies,
      estimate changes in usage patterns or intakes over time, and generalize from
      published results to marketed products is problematic.

PMID- 17209209
TI  - Multivitamin-multimineral supplements: who uses them?
AB  - Dietary supplement use is increasingly common in the United States. Multivitamin
      formulations with or without minerals are typically the most common type of
      dietary supplement reported in surveys and studies that collect data relating to
      dietary supplement use. In the National Health and Nutrition Examination Survey
      (NHANES) 1999-2000, 52% of adults reported taking a dietary supplement in the
      past month, and 35% reported regular use of a multivitamin-multimineral (MVMM)
      product. NHANES III data indicate an overall prevalence of dietary supplement
      usage of 40%, with prevalence rates of 35% in NHANES II and 23% in NHANES I.
      Women (versus men), older age groups, non-Hispanic whites (versus non-Hispanic
      blacks or Mexican Americans), and those with a higher education level, lower body
      mass index, higher physical activity level, and more frequent consumption of wine
      had a greater likelihood of reporting use of MVMM supplements in NHANES 1999
      2000. Data from children suggest a similar prevalence rate, but lower prevalence
      rates of usage were reported in studies of adolescents. Individuals who use
      dietary supplements (including MVMM formulations) generally report higher dietary
      nutrient intakes and healthier diets in studies in which dietary data were also
      collected. Among adults with a history of breast or prostate cancer, usage rates
      for dietary supplements in general and MVMMs are considerably higher (eg, 56-57%
      for MVMMs), and these subgroups are more likely to also report use of single
      vitamin and mineral supplements. Thus, MVMM use contributes a considerable
      proportion of nutrient intakes in the United States and may contribute to risk of
      excessive intakes.

PMID- 17209210
TI  - Multivitamin-multimineral supplements' effect on total nutrient intake.
AB  - Use of multivitamin-multimineral supplements is widespread and can contribute
      substantially to total nutrient intakes. In the Hawaii-Los Angeles Multiethnic
      Cohort (MEC), 48% of men and 56% of women without chronic diseases reported use
      of multivitamin supplements at least weekly over the past year. We calculated the
      prevalence of nutrient adequacy for 17 nutrients based on responses to a self
      administered quantitative food-frequency questionnaire administered to MEC
      participants at baseline in 1993-1996. Although the prevalence of nutrient
      adequacy from food only was higher for multivitamin supplement users (n = 21,056)
      than for nonusers (n = 69,715), differences averaged only 2 percentage points.
      For multivitamin users, the prevalence of adequacy improved by an average of 8
      percentage points for both men and women when intake from supplements was
      included. Users were also more likely to have potentially excessive intakes,
      particularly for iron, zinc, vitamin A, and niacin. The 26,735 MEC participants
      in Hawaii who answered an open-ended question about multivitamin use in 1999-2001
      reported using 1246 different products. The nutrient profile of these products
      varied widely, and the composition of products at the 90th percentile was 10-fold
      greater than the composition at the median for some nutrients. We conclude that
      analyses of nutrient adequacy and excess for supplement users should be extended
      to national samples and that composition data on actual supplements used are
      preferable to assuming a default nutrient profile for multivitamin supplements.
      Multivitamin products could be better formulated to reduce the prevalence of
      inadequacy and also to reduce the risk of excessive intakes.

PMID- 17209211
TI  - Folate and neural tube defects.
AB  - A protective effect of folate against the development of neural tube defects
      (NTDs), specifically, anencephaly and spina bifida, is now well recognized,
      having been established by a chain of clinical research studies over the past
      half century. This article summarizes the more important of these studies, which
      have led to the current situation in which all women capable of becoming pregnant
      are urged to ingest folic acid regularly. The recommended intakes are 4 mg/d for
      those at high risk (by virtue of a previous NTD pregnancy outcome) and 0.4 mg/d
      for all others. However, a reduction in NTD births did not follow promulgation of
      these recommendations, and so folic acid fortification was mandated in the United
      States and some other countries. Although some controversy remains about the
      adequacy of fortification levels, the process was followed by significant
      improvement in folate indexes and a reduction of 25-30% in NTD frequency (about
      one-half of the proportion of cases assumed to be responsive to folate). The
      folate-NTD relation represents the only instance in which a congenital
      malformation can be prevented simply and consistently. Nevertheless, several
      research gaps remain: identification of the mechanism by which the defect occurs
      and how folate ameliorates it; characterization of the relative efficacy of food
      folate, folic acid added to foods, and folic acid by itself; delineation of the
      dose-response relations of folate and NTD prevention; and more precise
      quantification of the dose needed to prevent recurrences.

PMID- 17209212
TI  - Vitamin and mineral supplements for cancer prevention: issues and evidence.
AB  - Trials of nutritional supplements for cancer prevention must overcome a variety
      of challenges not shared in the usual paradigm of pharmaceutical agents for
      prevention of cardiovascular disease. Unlike for cardiovascular disease, for
      cancer we typically do not have well-established causal risk factors as targets
      for intervention. Also, for most likely cancer interventions, the expected time
      to achieve an effect is much longer, more variable, and far less well understood
      than for cardiovascular disease, and the progression of pathophysiology is much
      harder-or impossible-to follow, in contrast with imaging for progression of
      atherosclerosis in cardiovascular disease. Also, cancers at various sites have a
      wide range of etiologies. The optimal age for intervention, best dose, and
      duration needed to test nutritional agents for cancer prevention are largely
      unknown, making null findings hard to interpret. Unlike with drugs, baseline
      nutritional status can be critical. Moreover, because the nutritional agents are
      often readily available, adherence in control groups in trials can be impaired.
      Several gene-nutrient and nutrient-nutrient interactions have been identified
      that could affect trial results. Some studies suggest that particular nutrients
      may be effective only in subgroups defined by genotypes or by nutritional status
      of another nutrient. All these challenges must be considered in planning
      informative trials. Long-term prospective cohort studies, especially with
      repeated measures and high follow-up, can provide useful data for planning trials
      as well as the basis for rational recommendations while awaiting trial results or
      in settings where trials may be infeasible.

PMID- 17209213
TI  - Heart disease and single-vitamin supplementation.
AB  - Heart disease is the number one cause of death in the United States and has long
      been recognized to be multifactorial. A growing body of evidence suggests that
      not only free radical-mediated reactions but also inflammatory responses play
      major roles in atherogenesis. Vitamin E has both antioxidant and antiinflammatory
      properties and is the most widely studied vitamin in clinical trials and thus
      will be the primary example used in this review. Clinical trials of vitamin E
      efficacy, in hindsight, have been overly optimistic in their expectation that a
      vitamin could reverse poor dietary habits and a sedentary lifestyle as well as
      provide benefit beyond that of pharmaceutical agents in treating heart disease.
      However, it is also apparent that most Americans do not consume dietary amounts
      adequate to meet established vitamin E requirements. In response to oxidative
      stressors, vitamin E can decrease biomarkers of lipid peroxidation, is itself
      killed, and requires optimal vitamin C status to function most effectively. Thus,
      adequate vitamin E intakes are clearly needed, but what is adequate for what
      function has yet to be defined. It is noteworthy that in most trials, biomarkers
      were not used nor were oxidative stress and lipid peroxidation markers used or
      plasma vitamin E concentrations measured.

PMID- 17209214
TI  - Bone health.
AB  - Much evidence indicates that both calcium and vitamin D are efficacious in
      protecting the skeleton, particularly when these 2 nutrients are used in
      combination. Each nutrient is necessary for the full expression of the effect of
      the other, and where their actions are independent, their effects on skeletal
      health are complementary. Nutrient status for both tends to be deficient in the
      adult population of the industrialized nations. Hence, supplementation or food
      fortification with both nutrients is appropriate and, given contemporary diets
      and sun exposure, probably necessary. Various meta-analyses, systematic evidence
      reviews, and controlled trials evaluating these 2 nutrients will be defective if
      they fail 1) to take into consideration the nearly universal need to augment the
      status of both nutrients in the populations studied rather than just one or the
      other, 2) to consider the threshold characteristics of both nutrients, and 3) to
      use the achieved serum 25-hydroxyvitamin D concentration as the independent
      variable for vitamin D effects (instead of oral vitamin D intake). Problems with
      adherence to a regimen of taking supplements daily make an appropriate
      fortification strategy the preferred option for improving the status of both
      nutrients.

PMID- 17209215
TI  - Multivitamin-multimineral supplements and eye disease: age-related macular
      degeneration and cataract.
AB  - The prevalence and effects of age-related macular degeneration (AMD) and cataract
      are increasing dramatically as the proportion of elderly in our population
      continues to rise. A multivitamin-multimineral supplement with a combination of
      vitamin C, vitamin E, beta-carotene, and zinc (with cupric oxide) is recommended
      for AMD but not cataract. Weak support exists for multivitamins or other vitamin
      supplements from observational studies of cataract. The results of observational
      studies suggest that a healthy lifestyle with a diet containing foods rich in
      antioxidants, particularly lutein and zeaxanthin, as well as n-3 fatty acids,
      appears beneficial for AMD and possibly cataract. The Age-Related Eye Disease
      Study II will evaluate some of these additional nutrients as dietary supplements
      in a randomized trial.

PMID- 17209216
TI  - Clinical trials and observational studies to assess the chronic disease benefits
      and risks of multivitamin-multimineral supplements.
AB  - Multivitamin-multimineral (MVM) supplements are widely used in the United States,
      often in the hope of reducing the risk of cancer, cardiovascular disease, or
      other chronic disease. This article assesses the potential of randomized
      controlled trials and epidemiologic cohort studies for yielding reliable
      information on the effects of MVMs on chronic disease. A brief review of the
      available literature on MVMs in relation to incidence and mortality rates from
      prominent cancers and cardiovascular diseases is also provided along with a
      discussion of needed research. Specifically, the strengths and weaknesses of
      epidemiologic cohort studies and randomized controlled trials are summarized and
      discussed in the context of single-vitamin supplements when both types of studies
      are available. Recent review articles that include an assessment of MVMs in
      relation to cancer and cardiovascular disease are updated to provide a summary of
      available data. Few randomized controlled trials and few cohort studies of MVMs
      that are directly pertinent to cancer or cardiovascular disease are available.
      The data are not compelling concerning a role for MVMs in preventing cancer or
      cardiovascular disease morbidity or mortality, although some interesting leads
      merit further evaluation. Investigators responsible for cohort studies that
      assessed MVMs should be encouraged to report available data on MVMs and chronic
      disease. Depending in part on the results of such additional reports, a full
      scale randomized controlled trial of well-selected MVMs in women may be warranted
      on public health grounds.

PMID- 17209218
TI  - What is known about the safety of multivitamin-multimineral supplements for the
      generally healthy population? Theoretical basis for harm.
AB  - Assessment of the safety of nutrients presents a challenge different from that
      posed by the assessment of other chemicals in food such as additives or
      contaminants. Because nutrients are essential, a dose-response relation exists at
      both ends of the intake range, separated by a safe range of intake that reflects
      normal homeostatic processes. The safe intake may not be the same for all
      population groups and life stages. The size of the safe intake range for each
      nutrient will vary and in a few cases may be very small. Certain nutrients such
      as vitamin A and manganese have known and potentially serious adverse effects at
      high intakes, whereas others such as iron or vitamin C may have more minor
      adverse effects that are readily reversible and may only be associated with
      supplement intake. The risk of harm occurring from taking dietary supplements
      will depend on the safe intake range of the nutrient concerned, the
      susceptibility of the individual, and the likely intake of the same nutrient from
      other supplements or the rest of the diet. In many cases, the available database
      for the safety of nutrients is very limited because the studies, where available,
      were not designed to assess adverse effects but may have detected problems when
      they occurred. Further information on the safety of nutrients could be obtained
      through careful experimental design.

PMID- 17209217
TI  - Clinical trials of vitamin and mineral supplements for cancer prevention.
AB  - Approximately 20-30% of Americans consume multivitamin supplements daily,
      indicating high public interest in the prevention of cancer and other chronic
      diseases through a nutrition-based approach. Although several bioactive food
      components, including vitamins and minerals, have been investigated for their
      ability to affect cancer risk, few large, randomized, placebo-controlled clinical
      trials of multivitamins with cancer as the primary endpoint have been performed.
      The results of most large-scale trials of multivitamin supplements (combinations
      of > or = 2 vitamins and minerals) to prevent cancer have been mixed. The Linxian
      General Population and Dysplasia trials found a decreased risk of cancer,
      particularly stomach cancer, for participants taking a multivitamin supplement,
      but this was in a borderline-deficient population in China. Two trials, the Alpha
      Tocopherol, Beta-Carotene Cancer Prevention Study and the beta-Carotene and
      Retinol Efficacy Trial, found an increased risk of lung cancer among male
      cigarette smokers or asbestos-exposed persons taking beta-carotene-a surprising
      result, considering that most epidemiologic studies have suggested that
      consumption of fruit and vegetables appears to lower cancer risk. To clarify the
      effects of multivitamin supplements, several large randomized clinical trials are
      underway, including the Physicians' Health Study II, the Selenium and Vitamin E
      Cancer Prevention Trial, and a European study, Supplementation en Vitamines et
      Mineraux Antioxydants (SU.VI. MAX). Because epidemiologic studies generally
      evaluate foods rather than specific bioactive food components, a systematic
      approach to determining how combinations of vitamins and minerals may interact to
      ameliorate cancer risk is necessary to further our understanding of the potential
      benefits and risks of supplement use.

PMID- 17209219
TI  - Adverse event monitoring and multivitamin-multimineral dietary supplements.
AB  - A study commissioned by the Food and Drug Administration (FDA) estimated that the
      FDA is notified of < 1% of all adverse events associated with dietary
      supplements. Among the factors that may contribute to underreporting are that
      many consumers presume supplements to be safe, use these products without the
      supervision of a health care professional, and may be unaware that the FDA
      regulates them. In 2001 an Office of the Inspector General report identified many
      of the difficulties in evaluating adverse events in a voluntary system and the
      barriers to effective analysis of these reports to generate possible signals of
      concern. These include factors such as limited medical information, limited
      product information, limited manufacturer information, limited information on
      dietary supplement consumers, and limited ability to analyze trends. In addition,
      for dietary supplements, vital premarket information (which is available for drug
      products) is often missing so that possible public health concerns generated by
      the adverse event reporting system, such as limited clinical information, product
      identification, and information on consumer use, cannot be adequately assessed.
      Thus, the FDA is inherently limited in its ability to investigate signals of
      public health problems generated by the system. However, the FDA can use adverse
      event reports to identify areas of concern warranting further investigation. The
      FDA then initiates collaboration with federal partners to identify knowledge gaps
      in the safety of individual dietary ingredients and products and works with these
      partners to fill these information gaps to support appropriate regulatory action.

PMID- 17209220
TI  - Challenges and opportunities in the translation of the science of vitamins.
AB  - Some 100 y after the description and naming of the first vitamin, this conference
      on the state-of-the-science has shown that remarkable and exciting advances have
      been made in our understanding of the biology, chemistry, and metabolism of
      vitamins, explaining their essentiality in the diet. A great deal more needs to
      be done in the translation of this knowledge into an understanding of the benefit
      of vitamin supplements to disease prevention and to health and well-being. Not
      only are advances in fundamental science and biology necessary, but more
      attention must be paid to genomics, epigenetics, behavioral science, and new
      techniques for evidence analysis of studies. Information relating individual
      vitamins or small combinations of vitamins to disease prevention is stronger than
      that for multivitamins, formulations that cry out for greater standardization.
      This large task of translating emerging science to better policy in the field of
      vitamin and multivitamin-mineral supplement use should occupy our attention
      intensively in the years to come. Issues needing more attention include the
      content and labeling of such products and the effects of the products on nutrient
      adequacy as well as in chronic degenerative disease prevention. In this quest,
      the development of more and better surrogate markers will be critical. Dose
      response assessments of safety are badly needed for updating Tolerable Upper
      Intake Levels. At its best, all of these disparate types of research will require
      a robust interaction between the public and private sectors in a regulatory
      framework that supports and rewards investment in good science.

PMID- 17209221
TI  - Approach to the patient with subclinical hyperthyroidism.
AB  - Endogenous subclinical hyperthyroidism, defined by normal circulating levels of
      free T4 and T3 and low levels of TSH, is a common clinical entity and is
      typically caused by the same conditions that account for the majority of cases of
      overt hyperthyroidism: Graves' disease, toxic multinodular goiter, and solitary
      autonomously functioning thyroid nodules. Subclinical hyperthyroidism has been
      associated with an increased risk of atrial fibrillation and mortality, decreased
      bone mineral density in postmenopausal women, and mild hyperthyroid symptoms.
      Treatment of subclinical hyperthyroidism remains controversial, given the lack of
      prospective randomized controlled trials showing clinical benefit with
      restoration of the euthyroid state. Nevertheless, it seems reasonable to treat
      older individuals whose serum TSH levels are less than 0.1 mU/liter and certain
      high-risk patients, even when the serum TSH is between 0.1 and the lower limit of
      the normal range.

PMID- 17209222
TI  - Diagnosing thyroid dysfunction in pregnant women: Is case finding enough?

PMID- 17209223
TI  - Breast cancer and the risk of osteoporotic fracture: A paradox.

PMID- 17209224
TI  - Secular decline in male reproductive function: Is manliness threatened?

PMID- 17209226
TI  - Pilot study of indoor radon in Greek workplaces.
AB  - Radon and gamma dose rate measurements have been performed in 561 workplaces in
      19 prefectures of Greece. The distribution of radon concentration can be well
      described by a log-normal distribution. Most of the radon concentrations are
      between 50 and 200 Bq m(-3) with an arithmetic mean of 123 Bq m(-3). The maximum
      measured value of radon gas concentration is 695 Bq m(-3). About 10% of the
      workplaces exceed 200 Bq m(-3). Only a small fraction ( approximately 1%) of
      workplaces exceed the European Commission action level (400 Bq m(-3)). Despite
      the relative small fraction of workplaces which exceed the value of 400 Bq m(-3),
      it is clear from the results of the present work that for certain prefectures,
      further and more extensive research is needed.

PMID- 17209225
TI  - Medical costs of obese Japanese: a 10-year follow-up study of National Health
      Insurance in Shiga, Japan.
AB  - BACKGROUND: For the Japanese population, a body mass index (BMI) of 25.0-29.9 is
      classified as obesity and is a risk factor for cardiovascular disorders such as
      hypertension. METHODS: A cohort study to clarify obesity costs for a Japanese
      population was conducted utilizing baseline BMI and medical costs over a 10-year
      follow-up period. The participants were 4502 community dwelling Japanese National
      Health Insurance (NHI) beneficiaries aged 40-69 years. According to their
      baseline BMI values (kg/m(2)), participants were classified into the following
      three categories: BMI < 18.5, 18.5 < or = BMI < 25.0 and 25.0 < or = BMI. Medical
      costs per person per month were compared among the three categories. Excess
      medical costs attributable to the 25.0 < or = BMI category compared to the 18.5 <
      or = BMI < 25.0 category were estimated. RESULTS: Approximately 20% of the
      Japanese population studied had a BMI of 25.0 or over. A J-shaped relationship
      between BMI and personal total medical costs was observed. Personal total medical
      costs per month determined from the 10-year follow-up in each category were 189
      Euros (BMI < 18.5), 134 Euros (18.5 < or = BMI < 25.0) and 155 Euros (25.0 < or =
      BMI). A J-shaped pattern was observed after adjusting for age, sex, smoking and
      drinking habits, and excluding early deceased participants. Furthermore, smoking
      habit did not modify the J-shaped pattern of total medical costs. The estimated
      excess medical costs for the 25.0 < or = BMI category represented 3.1% of the
      total medical costs for the entire study population (634 105 Euros). CONCLUSION:
      The Japanese NHI beneficiaries with a BMI of 25.0 or over showed increased
      medical costs compared to those with a BMI of 18.5-24.9.

PMID- 17209227
TI  - Individual monitoring for internal exposure of workers: regulation and practice
      in Hungary.
AB  - Decree of Ministry of Health for the enforcement of the Act on Atomic Energy has
      put special emphasis on the regulation of monitoring for internal exposure in
      Hungary. The necessarily general prescription of the Decree called for a guidance
      to assist the work of the competent authority. The Guide was elaborated on the
      basis of the IAEA Safety Guide No. RS-G-1.2. According to the IAEA Safety Guide
      the decision factor shall first be determined for the potential radionuclides and
      practice applied. For routine monitoring the required frequency, method and MDA
      values, moreover for special monitoring the method and MDA values were derived
      for over 50 radionuclides considering two basic assumptions: the activity
      remaining in or excreted from the body could be determined by the given
      measurement method and the possible underestimation of intake shall be less than
      a factor of 3 within the monitoring interval.

PMID- 17209228
TI  - Surgical outcome and prognostic factors of frontal lobe epilepsy surgery.
AB  - Frontal lobe epilepsy (FLE) surgery is the second most common surgery performed
      to treat pharmacoresistant epilepsy. Yet, little is known about long-term seizure
      outcome following frontal lobectomy. The aim of this study is to investigate the
      trends in longitudinal outcome and identify potential prognostic indicators in a
      cohort of FLE patients investigated using modern diagnostic techniques. We
      reviewed 70 patients who underwent a frontal lobectomy between 1995 and 2003
      (mean follow-up 4.1 +/- 3 years). Data were analysed using survival analysis and
      multivariate regression with Cox proportional hazard models. A favourable outcome
      was defined as complete seizure-freedom, allowing for auras and seizures
      restricted to the first post-operative week. The estimated probability of
      complete seizure-freedom was 55.7% [95% confidence interval (CI) = 50-62] at 1
      post-operative year, 45.1% (95% CI = 39-51) at 3 years, and 30.1% (95% CI = 21
      39) at 5 years. Eighty per cent of seizure recurrences occurred within the first
      6 post-operative months. Late remissions and relapses occurred, but were rare.
      After multivariate analysis, the following variables retained their significance
      as independent predictors of seizure recurrence: MRI-negative malformation of
      cortical development as disease aetiology [risk ratio (RR) = 2.22, 95% CI = 1.40
      3.47], any extrafrontal MRI abnormality (RR = 1.75, 95% CI = 1.12-2.69),
      generalized/non-localized ictal EEG patterns (RR = 1.83, 95% CI = 1.15-2.87),
      occurrence of acute post-operative seizures (RR = 2.17, 95% CI = 1.50-3.14) and
      incomplete surgical resection (RR = 2.56, 95% CI = 1.66-4.05) (log likelihood
      ratio test P-value < 0.0001). More than half of patients in favourable prognostic
      categories were seizure-free at 3 years, and up to 40% were seizure-free at 5
      years, compared to <15% in those with unfavourable outcome predictors. These data
      underscore the importance of appropriate selection of potential surgical
      candidates.

PMID- 17209229
TI  - Co-infections. German doctors treat hepatitis C early, with some success.

PMID- 17209230
TI  - Anti-HIV agents. Vicriviroc: is the risk of cancer increased?

PMID- 17209231
TI  - Retraction.

PMID- 17209233
TI  - Diagnostic value of MRI in a pelvic mass of prostatic origin: Part 2.

PMID- 17209232
TI  - Toxicoproteomics--the next step in the evolution of environmental biomarkers.

PMID- 17209234
TI  - Porcelain veneers.

PMID- 17209235
TI  - Drug interactions. Introduction: careful combinations.

PMID- 17209236
TI  - Drug interactions. Super pills-the treatments of the future?

PMID- 17209237
TI  - Drug interactions. Is atazanavir best when boosted with ritonavir?

PMID- 17209238
TI  - Drug interactions. Atazanavir and acid-reducing agents.

PMID- 17209239
TI  - Drug interactions. Unexpected interaction between T-20 and some protease
      inhibitors.

PMID- 17209240
TI  - Drug interactions. Brecanavir--a new protease inhibitor.

PMID- 17209241
TI  - Drug interactions. Coming soon--a new formulation of Kaletra.

PMID- 17209242
TI  - Drug interactions. Kaletra and ezetimibe.

PMID- 17209243
TI  - Drug interactions. Coming soon--a new formulation of saquinavir (Invirase).

PMID- 17209244
TI  - 2006 Sewall Wright Award.     Brian Charlesworth.

PMID- 17209245
TI  - 2005 Sewall Wright Award.     Robert E. Ricklefs.

PMID- 17209246
TI  - Blepharitis, allergy, and dry eye: lumpers and splitters.

PMID- 17209247
TI  - Measuring intraocular pressure.

PMID- 17209248
TI  - Thalassemia.

PMID- 17209249
TI  - Phakic intraocular lens for myopia.

PMID- 17209250
TI  - Difficult anatomies: just hold your (patient's) breath.

PMID- 17209251
TI  - [Physical, manly, and moral education by the natural method of Georges Hebert,
      1902-19].

PMID- 17209252
TI  - [Family and education in Argentina, 1945-55: instruments for action of the
      Peronist state].

PMID- 17209253
TI  - A blessing in disguise? Empowering Catholic health care institutions in the
      current health care environment.
AB  - Health care institutions, including Roman Catholic institutions, are in a time of
      crisis. This crisis may provide an important opportunity to reinvigorate Roman
      Catholic health care. The current health care crisis offers Roman Catholic health
      care institutions a special opportunity to rethink their fundamental commitments
      and to plan for the future. The author argues that what Catholic health care
      institutions must first do is articulate the nature of their identity and their
      commitments. By a renewed commitment to the praxis of health care on their own
      distinctive terms, Roman Catholic health care institutions may reestablish a
      vision of human nature and human service in an increasingly secular society.
      Health care could then reclaim its place as a powerful setting for the expression
      of Roman Catholic faith, life and witness.

PMID- 17209254
TI  - Preforming the categories: eighteenth-century generation theory and the
      biological roots of Kant's a priori.

PMID- 17209255
TI  - [Charity as the calling of the lady: the social commitment of the noblewoman in
      19th-century Ghent, 1845-80].

PMID- 17209256
TI  - Improved implants (sort of).

PMID- 17209257
TI  - Gender, nursing and the PBRF.
AB  - Significant disparities between male and female academics exist with respect to
      remuneration, academic grading and PBRF scores--with women doing less well than
      men in each of these areas. There exists a range of gender-based distribution and
      outcome gaps within the university, and between universities and non-university
      tertiary education organisations. This situation, combined with a devaluing of
      academic subjects that have feminised knowledge bases, is suggestive of wider
      structural discrimination against women. In this article individualised
      explanations for the failure of women to progress are set in the context of a
      critical exploration of the PBRF evaluation methodology. It is argued that both
      academia and the PBRF research assessment exercise embody a form of academic
      masculinity that systematically disadvantages women in general and nursing in
      particular.

PMID- 17209258
TI  - Primary health care for youth in New Zealand. Are current health strategies
      working?
AB  - This article presents a critique of New Zealand health strategies in terms of how
      well they are serving youth. It is argued that over the last two decades
      successive changes in government policy, while aimed at improving people's
      health, have either not worked or had negative effects for specific population
      groups. There is now clear evidence that lower socio-economic status has an
      adverse affect on health, particularly among disadvantaged groups such as Maori
      and Pacific Islanders. In discussions about disadvantage and health inequalities
      youth as an age group is often ignored. Yet young people have special needs in
      relation to their developmental stage, the transition between child and adult.
      They have high potential for behaviours identified as placing them 'at risk'; and
      that may impact on their future health. The New Zealand Health Strategy released
      by the Government in 2000, and the Primary Health Strategy (King, 2001) were
      intended, through additional funding and emphasis on primary health care, to lead
      to better health for all New Zealanders. For some groups, such as youth, these
      gains have not been achieved, and in many instanced the situation has worsened.

PMID- 17209260
TI  - Historical investigations: risk management in a New Zealand hospital 1888-1904.
AB  - This article reports an historical research project in which four events within
      one hospital are examined from the point of view of what, today, would be termed
      'risk management'. The examples involve a nurse sustaining injury in the course
      of her work, a fire in the hospital and two instances of patient complaints--one
      concerning nursing care and the other relating to a time lag between admission to
      hospital and receiving medical attention. All would have their counterparts in
      situations dealt with by today's Risk Management Departments. Analysis of the
      processes followed in investigating these occurrences reveals what seem to be two
      major differences when compared to present day practices. As well as being
      smaller in scale and less bureaucratic the earlier investigations were based on a
      culture of blame. It is argued that modern risk management approaches rather than
      being geared toward apportioning blame are more focused on understanding what can
      be learned from the incident with respect to preventing recurrence.

PMID- 17209259
TI  - Fat simple--a nursing tool for client education.
AB  - Recent debate about "good fats" and "bad fats" has created uncertainty for nurses
      and clients as they struggle to make sense of the often contradictory statements
      in the media. This article summarises the current level of knowledge regarding
      dietary effects on serum cholesterol and presents the information in an eye
      catching table that can be used as an educational resource in heart disease
      prevention education. Information from a literature review was used to design a
      table that identifies how changes in diet and activity can alter components of a
      person's lipid profile. Nurses can use the resulting table as a simple tool to
      give clients targeted education based on their individual cholesterol results.
      This tool illustrates that not all dietary recommendations to the public are
      beneficial to serum cholesterol levels and it also explains why popular diets
      such as the Atkins, Mediterranean, and glycaemic index/load can produce more
      cardio-protective profiles than the traditional low fat diet. It should provide a
      way forward in an increasingly contentious area of practice.

PMID- 17209261
TI  - Building bridges--New Zealand Wound Care Society conference. Te Papa, Wellington:
      6-8 April 2006.

PMID- 17209262
TI  - Water, water.

PMID- 17209263
TI  - Occupational injuries by hour of day and day of week: a 20-year study.
AB  - OBJECTIVE: To examine by hour of day and day of week the 750,000 compensation
      claims that were lodged by male workers in Queensland, Australia, during the 20
      year period from 1968 to 1988, including an investigation into some possible
      reasons for the increased number of claims on Mondays and the reduced number of
      claims on Fridays. METHOD: The study was based on the collection entitled
      Industrial Accident Statistics (Bulletin 79), published annually by the
      Australian Bureau of Statistics, Queensland office. This was the only State
      collection to include data on compensated injuries categorised by hour of day and
      day of week. There was no Australia-wide dataset of compensated occupational
      injuries. RESULTS: Compensation claims were not evenly distributed through the
      working week. There were more injuries on Mondays (23.6% of the total) than on
      Tuesdays (21.8%), than on Wednesdays (20.3%), than on Thursdays (18%), than on
      Fridays (16.3%). There were more injuries in the mornings than in the afternoons
      for every day of the working week. CONCLUSIONS AND IMPLICATIONS: This study
      confirms the existence of a steady reduction in workers' compensation injury
      claims on successive days of the working week. One possible explanation for this
      finding is offered as a basis for further research into the reasons for this
      trend. Hopefully, the results of these and later studies may suggest remedial
      measures that will help reduce the number of occupational injuries.

PMID- 17209264
TI  - The quality of cause-of-injury data: where hospital records fall down.
AB  - OBJECTIVES: This research identifies the level of specificity of cause-of-injury
      morbidity data in Australia. The research explores reasons for poor-quality data
      across different causes-of-injury areas, including a lack of clinical
      documentation and insufficient detail in the classification system. METHODS: The
      2002/03 hospital morbidity dataset of 593,079 injury-related hospital admissions
      was analysed to examine the specificity of coded external cause-of-injury data.
      RESULTS: While overall specificity appeared high, the cause of 47,660 injuries
      was not specifically defined according to the code assigned. Only 56% of cases
      for whom injury was the result of an accidental fall were assigned a specific
      code to identify the causal detail; 19% were assigned an 'Other Specified' fall
      code, suggesting a lack of specific code availability; and 25% were assigned an
      'Unspecified Fall' code, suggesting a lack of clinical documentation to
      facilitate code selection. CONCLUSIONS: To improve the quality of injury-related
      hospital morbidity data, two main areas to focus resources are: 1) the
      development of more specific cause-of-injury codes; and 2) the provision of more
      detailed documentation from clinicians. IMPLICATIONS: Clinicians and clinical
      coders need to work together to improve the quality of injury-related coded data
      through the provision of specific codes and improved clinical documentation.
      Accurate and comprehensive data pertaining to the circumstances surrounding
      hospitalised injury events will benefit injury prevention and surveillance
      initiatives, provide justification for resources related to injury
      hospitalisation, and assist in external cause research in Australia.

PMID- 17209265
TI  - Socio-economic distribution of environmental risk factors for childhood injury.
AB  - OBJECTIVE: Childhood injury remains the single most important cause of mortality
      in children aged between 1-14 years in many countries. It has been proposed that
      lower socio-economic status (SES) and poorer housing contribute to potential
      hazards in the home environment. This study sought to establish whether the
      prevalence of observed hazards in and around the home was differentially
      distributed by SES, in order to identify opportunities for injury prevention.
      METHODS: This study was a cross-sectional, random sample survey of primary school
      children from 32 schools in Brisbane. Interviews and house audits were conducted
      between July 2000 and April 2003 to collect information on SES (income,
      employment and education) and previously identified household hazards. RESULTS:
      There was evidence of a relationship between prevalence of household
      environmental hazards and household SES; however, the magnitude and direction of
      this relationship appeared to be hazard-specific. Household income was related to
      play equipment characteristics, with higher SES groups being more likely to be
      exposed to risk. All three SES indicators were associated with differences in the
      home safety characteristics, with the lower SES groups more likely to be exposed
      to risk. CONCLUSION: The differential distribution of environmental risk factors
      by SES of household may help explain the SES differential in the burden of injury
      and provides opportunities for focusing efforts to address the problem.

PMID- 17209266
TI  - The prevalence and risk behaviours associated with the transmission of blood
      borne viruses among ethnic-Vietnamese injecting drug users.
AB  - OBJECTIVE: To measure the prevalence and determinants of blood-borne virus (BBV)
      transmission in ethnic Vietnamese injecting drug users (IDUs). METHODS: The study
      was conducted in Melbourne, Australia, in 2003. It was a cross-sectional design
      with participants recruited from street-based illicit drug markets predominately
      using a snowball technique. One hundred and twenty-seven participants completed a
      questionnaire that asked about illicit drug use and participants' blood samples
      were tested for HIV, HCV and HBV. RESULTS: One hundred and three (81.1%) ethnic
      Vietnamese IDU study participants were HCV positive and three (2.4%) were HIV
      positive. More than 60% had evidence of being infected with HBV (either in the
      past, acute infection or chronic infection). Almost 60% had injected daily over
      the past 12 months. Fifty-nine participants had recently travelled to Vietnam; 24
      (41%) had injected drugs in Vietnam; and three (12.5%) reported sharing injecting
      equipment in Vietnam. CONCLUSION: The prevalence of BBVs was higher in this
      study's IDU population compared with IDUs in Australia generally, despite the
      fact that the injecting risk behaviours were similar to IDUs more generally.
      IMPLICATIONS: Culturally sensitive drug treatment and education programs need to
      be developed in Australia for both ethnic Vietnamese IDUs and their families to
      reduce this group's risk of contracting a BBV.

PMID- 17209267
TI  - Immunisation of refugee and migrant young people: can schools do the job?
AB  - OBJECTIVES: To assess immunisation needs, primary health care (PHC) use and trial
      a school-based immunisation service for refugee and migrant young people
      attending an Intensive English Centre (IEC) high school in Western Sydney.
      METHODS: We surveyed students attending an IEC in Western Sydney, assessing self
      reported immunisation status and use of PHC services via questionnaires
      translated in six languages. Those students who were not immunised for hepatitis
      B and measles-mumps-rubella (MMR) were provided the first and second dose of a
      three-dose hepatitis B immunisation schedule and a single dose of MMR vaccine. We
      compared the immunisation requirements for MMR and hepatitis B with utilisation
      of PHC. RESULTS: One-hundred and sixty-five students (85%) returned the
      questionnaire. Forty-nine students (30%) reported previous immunisation with MMR
      and 29 (18%) with hepatitis B. As part of the school immunisation program, 142
      (74%) received MMR vaccine, 151 (78%) received the first dose of hepatitis B
      vaccine, 144 (95%) received the second dose of hepatitis B, and 34 (23%) received
      the third hepatitis B dose elsewhere. Sixty-six students (40%) reported seeing a
      doctor in the past year. Students who had not seen a doctor in the previous year
      were significantly more likely to request immunisation (p < 0.01). CONCLUSIONS
      AND IMPLICATIONS: Refugee and migrant young people attending an IEC in Western
      Sydney report low immunisation rates. Our study highlights the urgent need for
      education and health to work together to provide specialised immunisation
      services for refugee and migrant young people.

PMID- 17209268
TI  - Epidemic infectious syphilis in inner Sydney--strengthening enhanced
      surveillance.
AB  - OBJECTIVE: To report the results of a 2001-04 enhanced syphilis surveillance
      program in south-eastern Sydney and a subset of cases from the Sydney Sexual
      Health Centre (SSHC). METHODS: For all laboratory syphilis notifications, a
      questionnaire was sent to the referring doctor requesting demographic data,
      clinical information about disease classification and the presence of symptoms.
      Sex of partner/s and HIV status were collected from a subset of cases seen at
      SSHC. RESULTS: During 2001-04, 1,275 syphilis notifications were received and
      1,112 (87%) were able to be classified as 361 (28%) cases of infectious syphilis,
      221 (17%) non-infectious syphilis and 530 (42%) treated syphilis. From mid 2002,
      an increase in the number of infectious syphilis notifications was noted. Of the
      361 cases of infectious syphilis, most were in men (348, 97%). From a subset of
      47 cases of infectious syphilis from SSHC, 43 (91%) were in gay men and nine
      (21%) had concurrent HIV infection. CONCLUSIONS: Inner Sydney has recently
      experienced a rapid increase in infectious syphilis affecting a defined
      population: men, aged 30-39, English speaking and Australian born. These results
      support recent reports of outbreaks among men who have sex with men, but without
      routine collection of additional risk factors control programs may be misguided.
      IMPLICATIONS: In light of the review of the NSW Public Health Act 1991, it is
      recommended that reducing barriers to the collection of HIV status and sex of
      sexual partners in de-identified syphilis notifications be explored as a matter
      of urgency.

PMID- 17209269
TI  - Sedentary behaviours among Australian adolescents.
AB  - OBJECTIVE: To describe the prevalence and distribution (by demographic
      characteristics and body mass index [BMI] category) of sedentary behaviour among
      Australian adolescents aged 11-15 years. METHOD: Cross-sectional representative
      population survey of school students (n = 2,750) in New South Wales, conducted in
      2004. Students' self-reported time spent during a usual week in five categories
      of sedentary behaviour (small screen recreation [SSR], education, cultural,
      social and non-active travel). Height and weight were measured. RESULTS: Grade 6,
      8 and 10 students spent approximately 34 hours, 41 hours and 45 hours/week of
      their discretionary time, respectively, engaged in sedentary behaviour. Urban
      students and students from Asian-speaking backgrounds spent significantly more
      time sedentary than students from rural areas or other cultural backgrounds. SSR
      accounted for 60% and 54% of sedentary behaviour among primary and high school
      students, respectively. Overweight and obese students spent more time in SSR than
      healthy weight students. Out-of-school hours educational activities accounted for
      approximately 20% of sedentary behaviour and increased with age. Girls spent
      twice the time in social activities compared with boys. Time spent in cultural
      activities declined with age. CONCLUSION: Sedentary behaviours among young people
      differ according to sex, age and cultural background. At least half of all time
      spent in sedentary behaviours was spent engaged in SSR. BMI was significantly
      associated with sedentary behaviour among some children, but not consistently
      across age groups. IMPLICATIONS: A clear understanding of young people's patterns
      of sedentary behaviour is required to develop effective and sustainable
      intervention programs to promote healthy living.

PMID- 17209270
TI  - A systematic review of school-based studies involving alcohol and the community.
AB  - OBJECTIVE: To describe and critique methodological aspects of school-based
      interventions that involve a broader community initiative. METHODS: An electronic
      search of 11 databases and manual search of references for intervention studies
      published in peer-reviewed journals from January 2000 to August 2004. To be
      included in the review, alcohol needed to be a primary focus of the study, the
      intervention to be school based and include grades between five and 12, and the
      intervention needed to involve the community. RESULTS: Sixteen articles were
      selected for inclusion in the review. Methodologically, several studies excluded
      reporting important details (e.g. follow-up periods unclear), process measures
      were ignored by some studies (e.g. exposure to intervention), and some employed
      less than optimal outcome measures (such as attitudes and knowledge). Student
      education, some form of parental involvement and researchers providing resources
      to the school, were the most frequently employed intervention strategies.
      CONCLUSIONS: There is a clear need to conduct more rigorous evaluation studies
      and to increase reporting standards for school-based interventions. There is also
      tentative scope to include the community more broadly, rather than focus on
      established relationships within the school environment. IMPLICATIONS: As
      evidence suggests, there is limited effectiveness in school-based interventions.
      It may be beneficial to do lowest-cost interventions that have some evidence for
      effect, complemented by strategies identified by expert opinion, until further
      rigorous evidence arises.

PMID- 17209271
TI  - 'Occasional' and 'social' smokers: potential target groups for smoking cessation
      campaigns?
AB  - OBJECTIVE: To describe the characteristics of self-described 'occasional' and
      'social' Australian smokers. DESIGN: Analysis of a national cross-sectional
      survey of smoking patterns, conducted in Australia in 2004. SETTING AND
      PARTICIPANTS: Australian adults in 2004 who responded to a survey question about
      self-described smoking status. MAIN OUTCOME MEASURES: Demographic
      characteristics, patterns of alcohol and tobacco use, smoking cessation attempts
      in the past year, and interest in cessation. RESULTS: Smokers who described
      themselves as 'occasional' and 'social' smokers comprised 29% of all smokers. A
      significant proportion of occasional and social smokers had been daily smokers,
      but the majority either believed that they had 'already quit' or had no intention
      of quitting smoking. CONCLUSIONS: Self-ascribed occasional and social smokers
      potentially represent an important target group for cessation. These types of
      smokers may be more resistant to public health messages regarding cessation
      because they do not view their smoking behaviour as presenting a high risk.

PMID- 17209272
TI  - Pregnancy and contraceptive use in a national representative sample of Australian
      secondary school students.
AB  - OBJECTIVE: To determine rate of pregnancy and use of contraception in a
      nationally representative sample of school students. METHODS: Year 10 and 12
      students from a representative random sample of schools throughout Australia
      completed a survey concerning health and sexual behaviour. RESULTS: Thirty-five
      per cent of students had experienced sexual intercourse. Of these, 6.1% (males
      4.1%, females 7.8%) reported they had experienced sex that resulted in pregnancy,
      and a further 7.5% were unsure. Most sexually active students reported using a
      condom (65%), and a further 36.8% reported using the pill for contraception the
      last time they had sex. Relatively few students (17.2%) used a dual contraceptive
      (female method and condom). CONCLUSIONS: Rates of reported pregnancy among Year
      10 and 12 students are relatively high. Although the majority of students used
      some form of contraception when they had sex, a significant minority practised
      unprotected and unsafe sex. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Sex
      education concerning pregnancy and sexually transmitted infection risks must be
      delivered early enough to influence first and early sexual activity.

PMID- 17209273
TI  - Cost-effectiveness of a post-splenectomy registry for prevention of sepsis in the
      asplenic.
AB  - BACKGROUND: Overwhelming, sometimes fatal infections represent a lifelong risk
      after surgical removal of the spleen, or in patients who develop hyposplenism as
      a consequence of illnesses. This risk may be reduced by all or a combination of
      vaccination, antibiotic prophylaxis and education. We aimed to determine if a
      registry approach to delivering these interventions would be cost effective using
      our own experience and published data. METHOD: The decision model compared a
      cohort of 1,000 people covered by a registry to a cohort of 1,000 people with no
      registry. The impact of the registry was assessed in terms of achieved rates of
      vaccination, chemoprophylaxis and education, consequent outcomes of overwhelming
      post-splenectomy infection (OPSI) and mortality (years of life lived). The cost
      effectiveness of the registry compared with no registry was estimated in terms of
      additional cost per case of OPSI avoided and as additional cost per life year
      gained. RESULTS: In the first two years, the additional cost of the registry was
      dollar 152,611 per case of OPSI avoided or dollar 205,931 per life year gained.
      After this initial registration period the cost-effectiveness improves over time,
      such that over the cohort lifetime a post-splenectomy register is associated with
      an additional cost of dollar 105,159 per case of OPSI avoided or dollar 16,113
      per life year gained. CONCLUSION: A registry-based approach is likely to prove
      cost effective in terms of mortality and rates of OPSI avoided.

PMID- 17209274
TI  - Demographic factors as predictors for hospital admission in patients with chronic
      disease.
AB  - OBJECTIVE: To identify demographic predictors of hospital admission for chronic
      disease. METHODS: Hospital morbidity records were extracted from the WA Data
      Linkage System for the period 1994-99 for specific chronic diseases based on
      national priorities. Poisson regression was used to estimate the effects of
      Aboriginal and Torres Strait Islander (ATSI) descent, co-morbidity, geography,
      socio-economic status and possession of health insurance on hospital admission
      rates. RESULTS: This study has identified some of the main demographic risk
      factors for hospitalisation in patients with chronic disease as the following:
      being male, of ATSI descent, living in a relatively disadvantaged Census
      Collection District and having multiple co-morbidities. Depending on the disease,
      locational disadvantage and possession of private health insurance were also risk
      factors. CONCLUSIONS: The study indicates that a crucial component in keeping
      patients with chronic disease out of hospital is ensuring quality primary care
      for all members of the community, equipping patients with the necessary skills to
      self-manage their chronic condition. Particular attention must be given to
      developing programs that are accessible to the more disadvantaged members of the
      community. IMPLICATIONS: Programs aimed at keeping patients with chronic disease
      out of hospital must be targeted at the most vulnerable groups of the population
      if they are to be effective.

PMID- 17209275
TI  - Action on climate change: the health risks of procrastinating.
AB  - OBJECTIVE: The world's climate will continue to change because of human
      influence. This is expected to affect health, mostly adversely. We need to
      compare the projected health effects in Australia arising from differing climate
      change scenarios to inform greenhouse gas emission (mitigation) policy. METHODS:
      We estimated health effects in Australia (heatwave mortality, dengue transmission
      regions) around 2100 under various greenhouse gas scenarios: "strong policy
      action" (efforts made now to reduce emissions) and "no policy action" (emissions
      continue at present high levels with no climate change-specific policies).
      RESULTS: Compared with no policy action, mitigation could reduce the number of
      deaths caused by hot temperatures among older Australians by 4,000-7,000 a year
      (range reflects likely population size at 2100). Under a scenario of "no action",
      the zone of potential transmission of dengue fever expands 1,800 kilometres (km)
      south, as far as Sydney. In contrast, by markedly constraining greenhouse gas
      emissions now, this southward extension could be limited to 600 km (to
      Rockhampton). The number of displaced people within the Asia-Pacific region could
      increase (by orders of magnitude) under the "no action" scenario because of
      adverse socioecological circumstances aggravated by climate change. CONCLUSIONS:
      Additional health effects will accrue as a result of the projected climate change
      throughout this century, and individuals and health systems should be prepared
      for some level of adaptation. However, timely and strong policy action to reduce
      greenhouse gas emissions would diminish the extent and severity of estimated
      future health effects.

PMID- 17209276
TI  - Health of mothers of school-age children with disabilities.
AB  - OBJECTIVE: To investigate the self-reported health status of mothers of school
      age children with disabilities. METHOD: Seventy-four mothers in the Northern
      Metropolitan and Eastern Sydney regions completed the MOS 36-item Short Form
      Health Survey (SF-36). The survey was readministered 11 to 15 months later and
      completed by sixty-two mothers. RESULTS: On average, the mothers reported
      significantly poorer mental health by comparison with population norms for women
      in New South Wales and for mothers with partners Australia wide. CONCLUSIONS: In
      the absence of population data, the results of this study substantiate the
      findings of earlier studies based on clinical assessment and small group
      comparison designs.

PMID- 17209277
TI  - Teaching research and epidemiology to undergraduate students in the health
      sciences.
AB  - OBJECTIVE: To identify and address particular challenges in the teaching of
      epidemiological concepts to undergraduate students in non-clinical health
      disciplines. METHODS AND RESULTS: Relevant pedagogical literature was reviewed to
      identify a range of evidence-based teaching approaches. The authors also drew on
      their experience in curriculum development and teaching in this field to provide
      guidelines for teaching epidemiology in a way that is engaging to students and
      likely to promote deep, rather than surface, learning. Discussion of a range of
      practical strategies is included along with applied examples of teaching
      epidemiological content. CONCLUSIONS AND IMPLICATIONS: Increasingly, there is a
      greater emphasis on improved learning outcomes in higher education. Graduates
      from non-clinical health courses are required to have a core understanding of
      epidemiology and teachers of epidemiology need to be able to access resources
      that are relevant and useful for these students. A theoretically grounded
      framework for effective teaching of epidemiological principles to non-clinical
      undergraduates is provided, together with a range of useful teaching resources
      (both paper and web-based). Implementation of the strategies discussed will help
      ensure graduates are able to appropriately apply epidemiological skills in their
      professional practice.

PMID- 17209278
TI  - Tobacco advertising and promotion at point-of-sale.

PMID- 17209279
TI  - Pharmaceutical ads in ANZJPH.

PMID- 17209280
TI  - The extent of water fluoridation coverage in Australia.

PMID- 17209281
TI  - Abortion opinion research in Latin America and the Caribbean: a review of the
      literature.
AB  - Abortion laws in Latin America and the Caribbean (LAC) are highly restrictive and
      may not reflect public opinion on the issue. This article synthesizes the survey
      literature on attitudes toward abortion in the region. We searched standard
      computer indexing services and polled colleagues at regional meetings to identify
      every methodologically sound quantitative study of abortion opinion in LAC
      published between 1985 and 2005. Of the 26 studies that met inclusion criteria,
      none was conducted in the Caribbean, 11 were conducted in Brazil, 11 in Mexico, 3
      in Argentina, and 1 in Colombia. The majority of populations surveyed support
      abortion under a greater number of circumstances than are permitted in their
      respective countries, particularly in cases of rape and threat to life or health.
      Future abortion opinion surveys should ask about support for the legality of
      abortion rather than about abstract acceptance of abortion, and questions should
      be worded carefully to capture the complexities of the public's views on this
      issue.

PMID- 17209282
TI  - Gender, migration, risky sex, and HIV infection in China.
AB  - Gender differences in sexual behavior as a consequence of migration have been
      ignored in both the migration and the HIV literature in China. This study
      examines differences among temporary migrants in terms of sexual behavior and
      factors that make female migrants more vulnerable to the risk of acquiring HIV
      infection. Results suggest that the interplay of migration and gender renders
      female temporary migrants particularly vulnerable to engaging in casual and
      commercial sex. Although male temporary migrants do not differ from male
      nonmigrants in prevalence of casual and commercial sex, the prevalence rates of
      casual and commercial sex for female temporary migrants are found to be 14 and 80
      times those for female nonmigrants, respectively. Female temporary migrants'
      higher unemployment rate and concentration in the service and entertainment
      sectors are keys to understanding differences in the prevalence of casual and
      commercial sex among temporary migrants according to sex. Policy measures to
      promote female temporary migrants' equal access to employment are urgently needed
      to improve their economic well-being and to reduce their risky sexual behavior.

PMID- 17209283
TI  - Factors related to induced abortion among young women in Edo State, Nigeria.
AB  - Sub-Saharan Africa has the highest death rate from induced abortion in the world,
      and young women in southern Nigeria are particularly likely to terminate their
      pregnancies. This study assesses the prevalence of and factors associated with
      induced abortion among 602 young women aged 15-24 who were surveyed in Edo State,
      Nigeria, in 2002. We find that 41 percent of all pregnancies reported by the
      young women surveyed were terminated, and we estimate the age-specific abortion
      rate for 15-19-year-olds in Edo State at 49 abortions per 1,000 women, which is
      slightly higher than previous local estimates and nearly double the countrywide
      estimate for women aged 15-49. We construct explanatory multivariate models to
      predict the likelihood that a young woman has experienced sexual intercourse, has
      become pregnant, and has undergone an induced abortion, controlling for important
      demographic and risk-behavior factors. Young women unmarried at the time of the
      interview are found to be significantly more likely than married women to have
      had an abortion. Young women who have experienced transactional or forced sex are
      also significantly more likely to report ever having had an abortion, as are
      young women who have experienced more than one pregnancy. We conclude with
      suggestions for modifying the content and target populations of behavioral change
      messages and programs in the area.

PMID- 17209284
TI  - Sexual violence in Lesotho.
AB  - The magnitude and characteristics of sexual violence in two urban areas of
      Lesotho are described based on a random household survey of 939 sexually active
      women aged 18-35. Sexual violence is defined as nonconsensual sex ranging from
      the use of threats and intimidation to unwanted touching and forced sex. Twenty
      five percent of women surveyed reported ever being physically forced to have sex;
      13 percent reported that forced sex was attempted; 31 percent said that they were
      touched against their will; and 11 percent reported being forced to touch a man's
      genitals. Boyfriends were the most common perpetrators of actual and attempted
      forced sex (66 percent and 44 percent, respectively); known community members
      were the most common perpetrators of touching the respondent against her will (52
      percent). Currently married women and those with more education were less likely
      than others to report that sex was forced upon them by an intimate partner or by
      another type of perpetrator. Women living in areas where a program raising
      awareness about sexual violence was ongoing were more likely to report a history
      of sexual violence. Given the high prevalence of HIV in Lesotho, programs should
      address women's right to control their sexuality.

PMID- 17209285
TI  - Why are infant and child mortality rates lower in the MCH-FP area of Matlab,
      Bangladesh?
AB  - Infant and child mortality rates are significantly lower in the Maternal and
      Child Health-Family Planning (MCH-FP) area of Matlab, Bangladesh, than in a
      comparison area. The two areas are similar in terms of socioeconomic
      characteristics, but the MCH-FP area provides better maternal and child health
      and family planning services, resulting in different reproductive patterns,
      including lower fertility rates and longer intervals between pregnancies. We use
      data from the Matlab Demographic Surveillance System for nearly 126,000 singleton
      live births that occurred between 1982 and 2002 to investigate the extent to
      which the different reproductive patterns in the MCH-FP area explain why infant
      and child mortality rates are lower there. Differences in reproductive patterns
      account for a small portion (up to 20 percent) of the variation in these rates
      between the MCH-FP and comparison areas, suggesting that the majority of the
      difference is due to the quality of MCH services.

PMID- 17209286
TI  - Dominican Republic 2002: results from the Demographic and Health Survey.

PMID- 17209287
TI  - Egypt 2005: results from the Demographic and Health Survey.

PMID- 17209289
TI  - High court deems IR legislation legal--but is it fair?

PMID- 17209290
TI  - Let's talk nursing (Part 4): Professionalism.

PMID- 17209291
TI  - Critical issues in mental health nursing. Part II. Nursing issues in forensic
      mental health.

PMID- 17209292
TI  - What does the coroner do?

PMID- 17209293
TI  - Women's rights at work worth fighting for. Part 2.

PMID- 17209294
TI  - Cost of disorders of the brain in Luxembourg.
AB  - Brain disorders (psychiatric, neurological and neurosurgical diseases) are
      leading causes of disease and disability. According to WHO data they cause 35% of
      the burden of all diseases in Europe. The present study aims to estimate the cost
      of defined brain disorders and adds all selected disorders to arrive at the total
      cost for Luxembourg. A model combining published economic and epidemiological
      data retrieved from the OECD (Organization for Economic Co-operation and
      Development) and Eurostat databases on brain disorders in Europe (EU member
      countries, Iceland, Norway and Switzerland) was used. We transformed and
      converted data for a defined period into the same currency (Euro 2004) and
      adjusted country specific economic data for purchasing power and relative size of
      economy and imputed data where no local data were available. There are an
      estimated 123000 people in Luxembourg currently living with a brain disorder. The
      total annual cost of brain disorders is estimated at Euro 500 million in 2004 or
      an average of Euro 1100 per inhabitant. Mental disorders constitute 62% of the
      total cost (excluding dementia), followed by neurological diseases (excluding
      dementia) 22%, neurosurgical diseases excluding herniated discs 2.2%. Direct
      medical expenditures (outpatient care, hospitalization, drugs) have a share of
      32%, direct non-medical costs (social services, informal care, adaptation,
      transportation) 18% and indirect costs (sick leave, early retirement and
      premature death) 51%.

PMID- 17209295
TI  - Prenatal maternal serum screening during the second trimester of pregnancy using
      the Triple Test in Luxembourg.
AB  - Starting in 1991, it is now an established practice in Luxembourg to use prenatal
      maternal serum screening during the second trimester of pregnancy. Its
      reliability has been investigated. Half of the pregnant population is screened,
      with a call back rate (false positive rate) of 5.4%. The sensitivity of the
      screening is 81.5%, the specificity 94.6%, with a PPV of 1.5% and a NPV of 99.9%.
      This is in good agreement with international findings.

PMID- 17209296
TI  - [Veterinarians--notables of the cities and the country. Some stages in their
      social ascent from the second half of the 18th century to the start of the 20th
      century].
AB  - During the second half of the 18th century scientific veterinary medicine, a new
      profession was born as a result of economic and military needs--losses of cattle
      as a consequence of infectious diseases and the growing demand for treatment to
      be given to the horses of the armies. At first the members of the emerging
      occupation, who are generally of very modest origin, hardly differ from the
      traditional actors of animal health. At the beginning of the 19th century the
      governments employ a large number of veterinarians for official missions to
      combat infectious diseases. As from the second half of the 19th century the
      skills of the veterinarians as doctors for animals and zootechnicians are
      beginning to be recognized by the rural population, whose increased income allows
      them more easily to enlist a veterinarian's services. From the 1860s onwards they
      also start to play a role in the monitoring of public health by controlling
      foodstuffs of animal origin. But it is only at the beginning of the 20th century
      that new technological progress, motor vehicles and the telephone (first in the
      cities, then in the country by way of telephone boxes), makes their work quicker
      and more efficient. New and strong antiseptics for external and internal use
      which help to combat many infectious diseases will however appear only around the
      1950s.

PMID- 17209297
TI  - The thyroid and autoimmunity. The 6th Merck Thyroid Symposium from 15th to 18th
      of June 2006 in Noordwijk, NL.

PMID- 17209298
TI  - [First published results of the H5N1 mission in Nigeria: Luxembourg scholarly
      excitement excites world-wide progress].

PMID- 17209299
TI  - [Nucleotide sequence variants of the glucocorticoid receptor gene and their
      significance in determining glucocorticoid sensitivity].
AB  - Nucleotide sequence variants of the glucocorticoid receptor gene and their
      significance in determining glucocorticoid sensitivity. The physiologic response
      and sensitivity to glucocorticoids may significantly differ among species,
      individuals, tissues and cell types. The variability of the effect of endogenous
      and exogenous glucocorticoids is largely determined by genetic components, of
      which the authors review the knowledge on the glucocorticoid receptor gene. The
      authors describe the genomic and non-genomic pathways of receptor function, the
      significance of isoforms produced during receptor protein formation, the
      pathomechanism of glucocorticoid resistance syndrome and the results of clinical
      investigations related to receptor gene polymorphisms. Through subtle alteration
      of receptor function, the gene polymorphisms may increase or diminish sensitivity
      to glucocorticoids and may play a role in the pathogenesis of metabolic
      disorders. In their own studies the authors found, that the N363S polymorphism,
      which increases glucocorticoid sensitivity, may play a role in the pathogenesis
      of bilateral adrenal adenomas, it may modify the clinical phenotype of patients
      with congenital adrenal hyperplasia, and may have an impact on steroid-induced
      ocular hypertension. It is presumed that further research in other diseases will
      continue to complete our knowledge on the pathophysiology of glucocorticoid
      receptor gene polymorphisms.

PMID- 17209300
TI  - [Diagnosis and management of endocrine crises in adulthood].
AB  - Diagnosis and management of endocrine crises in adulthood. The homeostasis of the
      body is regulated by concerted action of the endocrine, nervous and immune
      systems. An imbalance in this equilibrium, as a consequence of disease or
      endocrine failure, may lead to crisis, characterized by sudden onset and severe
      symptoms. The classical endocrine emergencies are rare but life-threatening
      conditions. Prompt and aggressive treatment significantly reduces mortality.
      Immediate therapy might be necessitated in cases of suspected endocrine
      emergencies, even prior to laboratory confirmation. These patients generally
      require admittance to an intensive care unit. In the present review only the most
      severe forms of life-threatening endocrine emergencies, including acute adrenal
      insufficiency, pituitary apoplexy, pheochromocytoma crisis, thyroid storm and
      myxedema coma will be discussed.

PMID- 17209301
TI  - [Lichen sclerosus in urological practice].
AB  - Lichen sclerosus in urological practice. INTRODUCTION: Lichen sclerosus is a
      sclerosing, inflammatory skin disease with unknown origin which causes secondary
      phimosis of the foreskin and stricture of the urethra. In the case of long term
      existence of it the prevalence of intraepithelial squamous cell neoplasia is
      increased. AIM: To identify the role of lichen sclerosus in adulthood phimosis
      and to categorize urological treatment. To define the proper therapy of lichen
      sclerosus, causing meatal and urethral stricture. To measure the incidence of
      lichen sclerosus in patients with squamous cell neoplasia. METHOD: There was
      looked the incidence of lichen sclerosus in patient suffering with phimosis,
      recurrent urethral stricture, therapeutical options and presence of lichen
      sclerosus in patient with penile squamous cell neoplasia. RESULTS: There were 123
      foreskins sent for histological examination from 624 patients operated with
      circumcision in the last 5 years in the clinic. There were 76 (62%) times lichen
      sclerosus justified in 123 foreskins. There were lichen sclerosus found in 90%
      (9/10) of excised tissues of recurrent urethral strictures. There were lichen
      sclerosus noticed in 3 of 10 (33%) penile squamous cell carcinoma slides.
      CONCLUSIONS: Lichen sclerosus can be detected in significant proportion of
      phimosis in adulthood. Lichen sclerosus can be found very often as the cause of
      recurrent urethral strictures, which takes necessary to perform 2 steps
      reconstructive operation with complete excision of the urethra and buccal graft
      emplacement. In the third of our all squamous cell carcinoma cases lichen
      sclerosus could be histologically shown, which give good reason for the
      opportunity of malignant disease development of this dermatological illness.

PMID- 17209302
TI  - [The role of ultrasonography in second trimester screening for fetal chromosome
      aberrations].
AB  - The role of ultrasound examination in second trimester screening for fetal
      aneuploidies. OBJECTIVE: Authors sought to determine the frequency of ultrasound
      findings in major chromosomal defects. They also tried to evaluate possible
      patterns of ultrasound signs of fetal chromosomal defects. METHODS: Through the
      time period of 15 years (1999-2004) 22,150 fetal karyotypings were done, and 514
      abnormal karyotypes (2.3%, 514/22,150) were diagnosed prenatally. Congenital
      anomalies of these fetuses, detected by second trimester sonography, were
      analyzed in this study. RESULTS: Of the 514 chromosome aberrations, 207 fetuses
      with trisomy 21 (40.3%), 70 fetuses with trisomy 18 (13.6%), 28 fetuses with
      trisomy 13 (5.4%), 69 fetuses with Turner syndrome (13.4%) and 12 fetuses with
      triploidy (2.3%) were detected. The incidences of major structural defects and
      minor anomalies were evaluated then ultrasound signs with the highest incidences
      were established in each of the major chromosomal defects. CONCLUSION: This study
      may help to select the "optimal components" of the genetic sonogram that would
      assist the counseling of women for the risk of a chromosomal abnormality. Other
      advantages of such approach could be the standardization of the contents of
      ultrasound examination among different health care providers and institutions,
      and a decrease in false-positive rates.

PMID- 17209303
TI  - [Artistic representation of disease, injury and disability].

PMID- 17209305
TI  - Estimation of the rate of mother to child transmission of HIV in Nigeria.
AB  - Definitive diagnosis of HIV infection in infants < 18 months of age who were born
      to HIV-infected mothers is still posing some difficulty in Nigeria and other
      developing countries. Within this age definitive diagnosis can only be carried
      out by antigen based techniques which are indeed not available in these
      developing countries. This has resulted in the absence of authoritative data on
      the rate of mother-to-child transmission in these countries. Nigeria inclusive.
      The present pilot study was therefore carried out to generate some information on
      the rate of mother to child transmission in Nigeria using the PCR technique.
      Plasma samples were obtained from 68 children of both sexes less than 18 months
      of age and who were born to HIV infected mothers. The samples were collected from
      two pediatric departments. in Lagos and in Benin. The presence of HIV 1 RNA in
      each of the samples. was determined using the Amplicor Monitor V 1.5 technique
      (Roche Diagnostics). Data showed that HIV-1 RNA was detected in 15 of the 68
      samples tested. This gave an HIV-1 RNA detection rate of 22%. Among women who had
      some intervention, the rate of transmission of infection was 11% while the rate
      among those without intervention was 30%. The 22% transmission rate recorded in
      this study is close to the range of 25 to 35% that has been reported in several
      developed and a few developing countries. A multicenter nationwide study will
      still be needed to determine the national mother to child transmission rate in
      Nigeria.

PMID- 17209304
TI  - Hepatitis B virus infection: implications in chronic kidney disease, dialysis and
      transplantation.
AB  - Hepatitis B virus (HBV) infection occurs worldwide but is most prevalent in
      Southeast Asia and sub-Saharan Africa with reported prevalence rates varying from
      3 - 26 %. The higher prevalence of infection has been reported in patients with
      HBV and human immunodeficiency virus (HIV) co-infection. Hepatitis B virus not
      only affects the liver but has also been implicated in the pathogenesis of
      membranous, membranoproliferative and mesangial proliferative
      glomerulonephritides. Though controlling the spread of HBV infection in renal
      dialysis units has been one of the major triumphs in the management of end-stage
      renal disease, transmission of HBV can still occur through contamination of
      equipments and environmental surfaces and the use of multiple dose vials of
      drugs. Some reports have indicated that prior HBV infections have negative impact
      on graft and host survival following transplantation. Interferon can be used in
      the treatment of HBV-associated glomerulonephritides (HBV- GN) but is
      contraindicated in transplantation because of its immuno-modulatory effects.
      Despite the fact that patients with chronic kidney disease (CKD) have suboptimal
      response to HBV immunization, immunization is still beneficial to these patients.
      However, reports indicate that most patients with CKD were either not immunized
      or were given suboptimal doses. Control of HBV in the population by immunization
      can lead to a reduction in the prevalence of HBV- GN. In addition, immunization
      of patients with CKD will help in controlling HBV infection in dialysis settings
      and can lead to improved graft and host survival following transplantation.

PMID- 17209306
TI  - Biochemical and serological characterization of mycoplasma strains isolated from
      the genital tracts of humans in Nigeria.
AB  - Fifty-five (55) Mycoplasma strains isolated from the genital tracts of humans
      were biochemically characterized using various biochemical tests and also
      serologically identified by growth inhibition technique using 5 mycoplasma
      antisera namely M. hominis PG2 1: M. genitalium G37: M. penetrans GTU54 and 2
      strains of M. fermentans PG18 (HRC 6-62-S-170 and MB713-501-069). Biochemically,
      43 (78.2%) strains were identified as Mycoplasma hominis, 8 (14.5%) strains as M.
      fermentans and 4 (7.3%) as M. penetrans. The M. hominis strains hydrolyzed only
      arginine while the M. fermentans and M. penetrans strains in addition to arginine
      hydrolysis also broke down glucose fermentatively and oxidatively. The M.
      fermentans strains showed varying reactions to phosphatase activity and to the
      reduction of tetrazolium chloride. Serologically, 4 (7.3%) mycoplasma strains
      were confirmed as M. penetrans GTU54 and of the 8 M. fermentans strains, 4 (7.3%)
      were identified as M. fermentans PG18 serotype HRC 6-62-S-170 and the other 4
      (7.3%) as M. fermentans PG18 serotype MB 713-501-069. Only 13 (30.2%) of the 43
      M. hominis strains were identified as M. hominis serotype PG2 1. None was
      identified as M. genitalium. The heterogeneity of the mycoplasma strains
      especially M. hominis was observed in this study and the need for the use of
      multiple antisera in growth inhibition test is hereby supported.

PMID- 17209307
TI  - Some histological effects of chronic administration of chloroquine on the medial
      geniculate body of adult wistar rat.
AB  - Some histological effects of chronic administration of chloroquine commonly used
      for prophylaxis or treatment of malaria. rheumatoid arthritis and lupus
      erythematosus on the medial geniculate body (MGB) of adult wistar rats was
      carefully studied. The rats of both sexes (n= 18), average weight of 184g were
      randomly assigned into treatment (n= 10) and control (n=7) groups. The rats in
      the treatment group received 2mg/kg body weight of chloroquine base dissolved in
      distilled water daily for fourteen days through the orogastric tube
      administration while the control rats received equal volume of distilled water
      daily through the same route. The rats were fed with rat pellets purchased from
      Topfeed Ltd. Sapele. Delta State. Nigeria and given water liberally and were then
      sacrificed on day fifteen of the experiment. The MGB were carefully dissected out
      and quickly fixed in 10% formal saline for routine histological study after H & E
      and thionin methods. The histological findings after H & E methods indicated that
      the treated sections of the MGB showed faintly reduced nuclei size, with the
      presence of many autophagic vacuoles and degenerative neurons when compared to
      the control sections. On the other hand. the thionin method indicated that the
      treated sections showed sparsely distributed neurons, which stain less intensely
      when compared with the control. The nissl substance in some of the neurons
      appeared degenerative while some hypertrophied with some vacuolations. These
      findings indicated that chronic administration of chloroquine has a deleterious
      effect on the neurons and nissl substance of the MGB. Chloroquine may probably
      have adverse effects on auditory sensibilities by its deleterious effects on the
      nerve cells and nissl substances of the MGB of the adult wistar rats. It is
      recommended that further studies aimed at corroborating these observations be
      carried out.

PMID- 17209308
TI  - Bacterial isolates of blood cultures in patients with suspected septicaemia in
      Ilorin, Nigeria.
AB  - Periodic bacteriologic surveillance of blood cultures is a necessity. To
      determine currently prevalent bacterial pathogens of blood cultures in patients
      with suspected septicaemia in Ilorin. Nigeria. Three thousand and fifty-seven
      patients from all age and sex groups with clinical suspicion of septicaemia
      underwent bacteriologic screening of their blood specimen over a 13 month period
      starting from January. 2003. Twenty point three percent were positive for
      bacterial growth. An incidence of 41.7 per 1000 admissions was recorded which was
      a statistically significant (p< 0.05) marginal increase when compared with the
      previous incidence of 37.9 per 1000 admissions from this centre. Majority of the
      isolates were gram negative (51.61%) though the single predominant isolate was
      Staphylococcus aureus (35.85%). Other isolates included Escherichia coli
      (32.48%), Klebsiella pneumoniae (11.74%), Proteus spp (0.32%), coagulase negative
      Staphylococcus (1.61%), Salmonella typhi (0.48%). beta-hemolytic Streptococcus
      (0.48%) and Acinetobacter spp (0.32%). No anaerobe was isolated. Most isolates
      were sensitive to fluoroquinolones (ofloxacin, perfloxacin and ciprofloxacin) and
      third generation cephalosporins (ceftriaxone and ceftazidime) except
      Acinetobacter that was 100% resistant to both groups of antibiotics. Gram
      positive isolates were resistant to the second generation cephalosporin,
      cefuroxime. We hereby recommend the use of combination of a third generation
      cephalosporin and fluoroquinolones where not contraindicated, in the empiric
      treatment of septicaemia before sensitivity results are available.

PMID- 17209309
TI  - Cancer of the ovary at the University of Benin Teaching Hospital: a 10-year
      review, 1992-2001.
AB  - Forty-nine patients managed for primary ovarian cancer between January 1992 and
      December 2001 were analyzed, to appraise the incidence, clinical presentation and
      management. Data of relevance to the socio- demographic profile, clinical
      presentation, histopathological types, treatment modality and outcome of
      management were extracted from patients' case notes. A total of 412 patients with
      gynaecological malignancies, including 49 (11.9%) ovarian cancer were admitted in
      the gynaecological wards in the study period. The peak age of incidence was
      between 51- 60. mean 58 years. Social classes I and II were in the majority,
      21.7% and 32.6% respectively. Late presentation, with stage III (76.2% of the
      patients) is the modal stage at presentation. The majority (73.8%) of the tumours
      were of epithelial origin. Gastrointestinal symptoms (86.9%) were the most common
      clinical features at presentation. The majority of patients (91.3%) had surgery
      (cytoreductive) as first line treatment, while 36/42 patients had adjuvant
      chemotherapy. Intraoperative haemorrhage (11.9%) was the most common
      complication. 2.4% of the patients died intraoperatively Primary ovarian
      carcinomas in Benin are predominantly epithelial in origin. It is the second most
      frequent gynaecological malignancy. Patients present late. mortality is high and
      unsatisfactory despite multimodal therapy. Public enlightenment to increase
      awareness and introduction of screening program for early detection is advocated.

PMID- 17209310
TI  - Herbal remedy in the treatment of malaria: cross sectional survey of residents of
      Lagos State, Nigeria.
AB  - Semi structured questionnaires. designed to capture information on the type.
      composition, method of preparation. dosage, mode of administration. and frequency
      of use of herbal preparations in malaria treatment, were administered to 1,593
      adults of the 3 main ethnic groups and a forth group comprising other smaller
      ethnic groups designated as "others", all resident in Lagos metropolis in a cross
      sectional survey. The 1,593 respondents were made up of 892 males and 701 females
      and their ages ranged from 19 to 60 years. A high percentage in all the ethnic
      groups especially the Yorubas admitted to the use of herbs in treating malaria
      [Yoruba (69%), Hausa (47%). others (32%) and Igbo (30%)1. Effectiveness of herbs
      in treating malaria episodes featured as the major factor for their use. as
      claimed by the majority (>50%) of the respondents in each of the ethnic groups,
      while cost consideration was the next most important factor. Other factors
      mentioned included the absence of side effect in herbal use. to avoid the itchy
      side effect and ineffectiveness of chloroquine and some other anti-malarials. An
      appreciable percentage across the ethnic groups had no idea of the constituents
      of the herbal remedies they use for treating their malaria episodes since they
      buy these from traditional herbalists. Varied combinations of these herbs in
      combination with different types of fruits and other substances are claimed to be
      used, the main ones of which are Azardiracha indica and pineapple. A large
      majority of respondents in all the ethnic groups claimed to use the same herbs
      for the treatment and prevention of malaria and great improvement is experienced
      after use [Hausas (90%). Igbos (83%). Yorubas (77%) and the others (88%)]. There
      is usually no specific dose or dose regimen. however a high proportion in all the
      ethnic groups use herbal preparation thrice a day and a few of the respondents
      take unspecified measures at arbitrary intervals. The lack of standards in the
      use of these herbal preparations needs to be urgently addressed especially as use
      continued until the malaria symptoms and signs are deemed to have disappeared.
      There is also need to standardize the usage of herbs if they are to play a
      significant role in malaria prevention and treatment.

PMID- 17209311
TI  - Diabetes care in Nigeria: time for a paradigm shift.
AB  - Diabetes mellitus is becoming a major public health problem in Africa and its
      burden is expected to increase. Persons with diabetes mellitus require continuing
      medical care and self-management education to prevent complications. In both
      developed and some resource-poor countries, the management of persons with
      diabetes has been undergoing rapid changes in order to improve standards of care,
      through restructuring of clinics or through the establishment of diabetes centres
      with a multidisciplinary team approach to care. There has been a progressive
      increase in the prevalence of diabetes mellitus in Nigeria and the burden is
      expected to increase even further. In view of the looming burden of diabetes in
      Nigeria, there is an urgent need to examine existing healthcare structures,
      revise the delivery process of healthcare programmes for persons with diabetes
      and effectively implement a process that facilitates accessibility to such
      programmes. Well-structured community-based care, appropriate to the local
      situation and resources, would provide for this, making it more accessible and
      realistic to the needs of persons with diabetes living in urban and rural areas
      of Nigeria. Various models have been adopted for the delivery of diabetes care.
      This article aims to highlight some of these various models of diabetes care. It
      concludes with a proposed model for the care of persons with diabetes mellitus in
      Nigeria.

PMID- 17209312
TI  - Quality control of the total lymphocyte count parameter obtained from routine
      haematology analyzers, and its relevance in HIV management.
AB  - Lylmphocyte subsets/CD4 T Helper cell enumeration in HIV care and treatment in
      resource constrained settings can be difficult to ascertain as a result of the
      lack of the necessary instrumentation, capacity and infrastructure. However. it
      is imperative to gain such information for patient monitoring in HIV. The Total
      Lymphocyte Count (TLC) is useful as a surrogate marker for CD4 count as
      recommended by the World Health Organisation (WHO) and to calculate CD4% for
      pacdiatric use. This study therefore sets out to determine and compare the
      accuracy of the total lymphocyte counts obtained from three haematology analysers
      designated A. B and C. that are in regular use for routine haemnatological
      parameters at the main referral hospital in Barbados. West Indies. The TLC of 263
      HIV treatment naive individuals attending the HIV Reference Unit in Barbados were
      enumnerated on the three haematology analysers. The lymphosumn (Sum of lymphocyte
      subsets: T-helper cell. T-cytotoxic cells. B lymphocytes and Natural killer
      cells) should be equal to the TLC. and is derived by immunophenotypic analysis on
      a 4-colour flowcytometer. Machine C had the highest positive correlation between
      the TLC and the lymphosumn with and R' of 0.9031 compared to machine A with an R
      values of 0.7119 and Machine B with R(2) values of 0.637. These results show that
      there can be dramatic inaccuracies when using routine haematology analysers for
      both routine use. as a surrogate marker of CD4 or for derivation of CD4% in HIV
      management. It further demonstrates that all haematology analyzers require some
      form of Quality control. The possible lack of accuracy of the TLC by haematology
      analysers should be taken into consideration when following the recommendations
      of the WHO in resource poor settings or using it as a denominator for calculating
      CD4%.

PMID- 17209313
TI  - Concomitant craniospinal injuries with maxillofacial trauma--a review of 266
      cases.
AB  - Maxillofacial injuries are fairly common and they are usually found in
      association with multiple injuries. The proximity of the face to the craniospinal
      axis results in significant association between maxillofacial trauma and
      craniospinal injuries. Previous studies have enumerated this association but the
      injury types, classifications and influences of the concomitant injuries on the
      outcome of management are sketchy. In this study, road traffic accident was the
      commonest cause of maxillofacial and concomitant c raniospinal injuries: mild
      closed head injuries was the commonest concomitant injury occurring in almost 60%
      of the cases whilst mandibular fracture was the maxillofacial injury frequently
      encountered. The average duration of hospitalization in patients with
      maxillofacial trauma and concomitant mild head injury was 19 days but it was much
      higher (average 34.9 days) in patients with concomitant spinal injuries. The high
      incidence of head injury would suggest that maxillofacial units are best cited in
      hospitals with functional neurosurgical services.

PMID- 17209314
TI  - Trans-frontal extracranial approach in repair of cerebrospinal fluid fistula.
AB  - A 35 year old African woman presented with a 2 year history of unilateral watery
      left anterior rhinorrhoea, the only other significant feature being a history of
      severe head injury during childhood. Clinical and radiological evaluation
      confirmed a cerebrospinal fluid fistula, localized in the inferior portion of the
      posterior wall of the frontal sinus and ethmoid, no intracranial pathology.
      Repair was done successfully with a deep temporalis fascial graft through an
      external transfrontal approach. We report this to buttress the current trend in
      which less invasive external and endoscopic techniques are replacing intracranial
      methods. Reduction in morbidity and mortality which are the merits of this
      technique are emphasized and the management is discussed.

PMID- 17209315
TI  - Repeat ipsilateral ectopic gestation: a series of 3 cases.
AB  - Ectopic pregnancy remains an important cause of maternal mortality and morbidity
      as well as early foetal wastage in Nigeria and in other developing countries. We
      report 3 different cases of repeat ipsilateral ectopic pregnancy seen in the
      gynaecological emergency unit of the University College Hospital, Ibadan. Cases
      of repeat ectopic pregnancy often gives rise to diagnostic dilemma, and this
      becomes more difficult when it occurs at an ipsilateral location.

PMID- 17209316
TI  - Fibrodysplasia ossificans progressiva in a Nigerian: a case report.
AB  - A case offibrodysplasia ossificans progressiva in a 3-year and 10-month-old Igala
      boy is presented. It was characterized by progressive ossification of connective
      tissue and muscles of the neck and chest. Characteristic digital anomalies
      particularly microdactyly of the hallux and pollex, hallux valgus, and
      clinodactyly were also noted. The 2nd to 5th metacarpals had epiphyses at both
      the proximal and distal ends instead of only at the proximal ends. Although the
      patient presented in the first year of life, the diagnosis was not made until in
      his fourth year of life. Early diagnosis of the disease is important in order to
      avoid all forms of trauma that may worsen the prognosis.

PMID- 17209317
TI  - Cutaneous metastasis from hepatocellular carcinoma: a rare presentation and
      review of the literature.
AB  - A 53-year-old male Nigerian with a rare cutaneous metastasis and a late
      manifestation of hepatocellular carcinoma is presented. The skin nodules were
      umbilicated, painless. firm and spread on the chest, abdomen and back.
      Ultrasonography showed a huge mass in the right lobe of the liver. Fine needle
      aspiration cytology of the liver revealed hepatocellular carcinoma and the skin
      nodule, metastatic carcinoma of hepatic origin. The immunological marker HBsAg
      was positive while Anti-HCV Ab and alpha-feto-protein were negative. Patient died
      and consent for post-mortem examination was refused.

PMID- 17209318
TI  - Bilateral congenital cystic adenomatiod malformation of the lungs: a case report.
AB  - A six weeks old infant presented with scalp ulcer and fever. and on examination
      was found to have resonant percussion notes bilaterally. The initial chest
      radiograph revealed multiple lucencies which were initially thought to be due to
      diaphragmatic hernia, but the dilemma was resolved by Computerised tomography
      which revealed the lucencies to be multiple cysts characteristics of Congenital
      Cystic Adenomatiod Malformation (CCAM) type II.

PMID- 17209319
TI  - Malaria and anaemia in pregnancy in Enugu, south east Nigeria.
AB  - Malaria and anaemia contribute tremendously to maternal and prenatal morbidity
      and mortality. This study was carried out to document the magnitude of the
      problem in pregnancy with a view to identifying areas of intervention. The
      subjects were 108 consecutive pregnant women aged 18 to 44 years recruited from
      the antenatal clinics. 23 (21.3%) had malaria, 35 (32.4%) had anaemia while
      20(18.5%) had both malaria and anaemia. The highest incidence of malaria occurred
      in the second trimester, while anaemia was most prevalent in the third trimester
      (62.86%) and among primigravidae (37.14%). All the cases of malaria were due to
      plasmodium falciparum. Six out of the 20 women with both anemia and malaria were
      admitted and treated. Two low birth weight babies were delivered among the
      malaria and anaemia group. The incidence rates of malaria and anaemia were 215
      and 327 per 1000 pregnant women respectively while the incidence rate of anaemia
      due to malaria was 571 per 1000 infected pregnant women. There is a need for a
      more effective intervention to reduce the incidence of both malaria and anaemia
      in pregnancy.

PMID- 17209320
TI  - Evaluation of a rapid test kit for detection of HBsAg/eAg in whole blood: a
      possible method for pre-donation testing.
AB  - In many developing countries where hepatitis B is endemic, positivity rate for
      HBsAg in donor blood is high, and in some places, up to 20% of donated blood has
      to be discarded for being HBsAg positive. This degree of wastage may be
      financially crippling for some developing countries. Pre-donation testing may be
      useful, so that donors who test HBsAg positive are deferred and wastage of costly
      blood bags is reduced. The study is to evaluate the suitability of the AMRAD kit,
      for pre-donation testing for HBsAg. One hundred and one (101) healthy blood
      donors were screened for HBsAg/eAg using the test kit. The same specimens were
      screened using Monolisa (ELISA) kits for HBsAg and eAg as the standard. True
      positive (TrP), False negative (FN), True negative (TrN) and, false positive (FP)
      values were then found, from which, sensitivity and specificity, were derived.
      The AMRAD test kit detected 93 specimens as negative and 8 specimens as positive
      for HBsAg as against 94 negatives (TrN) and 7 positives (TrP) by monolisa. Thus,
      one false positive (FP) result was found in using the kit while no false negative
      (FN) occurred. The findings in this preliminary study suggest that AMRAD kit may
      be a useful predonation screening test for HBsAg.

PMID- 17209321
TI  - Should absolute lymphocyte count be used as a surrogate marker for CD4+ count in
      patients with HIV/AIDS?
AB  - The World Health Organization (WHO) has recommended the use of absolute
      lymphocyte count (ALC) as a potential marker for immunosuppression where CD4+
      count is unavailable. However, there are conflicting reports on the usefulness of
      ALC as a surrogate marker for CD4+ counts in patients with HIV/AIDS, more so, in
      patients with HIV-associated tuberculosis (TB). To evaluate the usefulness of ALC
      as an alternative to CD4+ counts and to see whether TB affects the correlation of
      ALC with CD4+ counts in patients with HIV-associated TB. A total of 66
      consecutive patients (33 with and 33 without TB) with a diagnosis of HIV
      infection were recruited into the study as cases. Another group of 66 subjects
      (33 subjects each) age- and sex-matched HIV-negative controls were recruited as
      controls and stratified in to two: a) HIV-negative PTB patients. b) apparently
      healthy HIV and PTB negative individuals. The age range was from 15-60 years
      (median: 32 years). The highest percentage (39%) of subjects fell in the age
      range of 25-29 years. The mean ALC for HIV-associated PTB was 3906 +/- 1092
      cells/microl and for patients with HIV infection only. 4755 +/- 1049
      cells/microl. There was no significant difference in mean ALC between males and
      females in both groups (P > 0.05). Patients with dual infection by M.
      tuberculosis and HIV had the lowest mean ALC (3906 +/- 1092 cells/microl).
      Healthy controls had mean ALC (+/- SD) of 5249 +/- 101 cells/microl. There was
      significant difference between the healthy controls and the other three groups.
      The observed difference was more in patients with HIV/ TB co-infection (P <
      0.005) compared with patients with HIV alone (P < 0.05). No significant
      correlation was observed between CD4+ cell counts and ALC in all the age groups
      of the study population. When the CD4+ counts were divided into < 200 and > or =
      200 cells/microl and the ALC into < 2000 and > or = 2000 cells/microl, the
      sensitivity, specificity and positive predictive values of the diagnostic
      usefulness of ALC in HIV-associated PTB were 52%. 56.3% and 78.8% while for HIV
      only patients the same values were 56.3%. 55.9% and 54.5%, respectively. We
      cannot recommend the use of ALC as a surrogate for CD4+ count in our environment
      as this study has clearly shown that the correlation between the two is weak.
      Patients with dual infection by HIV and M. tuberculosis are more likely to have
      lower CD4+ cell and AL counts than those with HIV infection occurring alone.

PMID- 17209322
TI  - A study of the microbial quality and organoleptic properties of ophthalmic
      preparations obtained from traditional medical practitioners in South Western
      Nigeria.
AB  - Twenty eight samples of traditional ophthalmic preparations were obtained from
      various traditional medical practitioners in the South Western states of Nigeria
      over a one-year period. They were examined for sterility, clarity, presence of
      particulate contamination and pH. All of them were found to be contaminated with
      bacteria to the order of 2.00 x 10(6) to 1.60 x 10(11) colony forming units/ml,
      with Pseudomonas species and other potential pathogens such as Staphylococcus
      aureus, Yersinia enterocolita, Micrococcus varians and others being isolated from
      these preparations. A rotifer Rotaria rotatoria, at the adult stage, was also
      isolated from one sample, this being an indication of gross faecal contamination.
      All the samples were also found to contain significant particulate contamination
      and pH values encountered varied over the range of 2.5-9.2. None of the samples
      was found to comply with official specifications and all of them may therefore be
      regarded as being potentially dangerous to the users.

PMID- 17209323
TI  - Intracranial tuberculomas: the Hofuf, Saudi Arabia experience.
AB  - Tuberculosis usually involves the brain through haematogenous spread. The mass
      lesion caused by tuberculosis in the brain is called tuberculoma, which is a
      conglomerate of tubercles. Tuberculomas may also be found in the spinal cord.
      Because of their slow growth they often become calcified. The study was conducted
      at the King Fahad Hospital, Hofuf, Al Hassia, Saudi Arabia between 1992 and 1998.
      It was a prospective study of all patients which had intracrainal mass lesions
      which showed typical ring-enhancement on brain CT scan with contrast. Twenty
      patients satisfied inclusion into the study. Of the 20 patients studied, 19 (95%)
      were males and 1 (5%) was a female. The ages ranged between 22 and 50 years.
      Eighteen (90%) of the patients were immigrant labourers from Asia and 2 (10%)
      were Saudi nationals, a male aged 50 years and a female aged 22 years. Fifteen
      (83.5%) were from India, 2 (11.1%) from Bangladesh, and 1 (5.6%) from Sri Lanka.
      The presenting feature in 60% of cases was focal seizure with secondary
      generalisation. 20% had primary generalized seizures, and 30% presented with
      headache, 25% with weakness of the limbs, 15% with fever and 10% each with
      vomitting and blurred vision, respectively. In 65% of cases, there was
      noneurological deficit but 35% had pyramidal weakness in the limbs. In 55% of
      cases the Tuberculomas were located in the left cerebral hemisphere. 30% in the
      right cerebral hemisphere and in 15%, the lesions were in both hemisphere. When a
      male Asian immigrant labourer aged between 20 and 40 years presents with seizures
      with or without headache, he should have a brain CT scan with contrast to exclude
      intracranial Tuberculoma. A short course of anti-tuberculous therapy may be tried
      where there is doubt, irrespective of normal erythrocyte sedimentation rate
      (ESR). We suggest that when the presenting symptom is primary generalized tonic
      clonic seizure, the intracranial Tuberculoma is located in the frontal lobe: a
      high erythrocyte sedimentation rate (ESR) may indicate multiple Tuberculomas.

PMID- 17209324
TI  - Impaired baroreflex sensitivity and responses to angiotensin converting enzyme
      inhibitor in salt-induced hypertension and its prevention by dietary calcium
      supplement in Sprague-Dawley rats.
AB  - The role of renin-angiotensin system and baroreceptors in the pathogenesis and
      prevention of hypertension due to salt-loading and concurrent dietary calcium for
      6 weeks in Sprague-Dawley rats were studied. Blood pressure measurements were
      done in anaesthetized animals while the activities of renin-angiotensin and
      parasympathetic nervous systems were determined by the effect of their inhibition
      on the arterial pressure and baroreflex sensitivity, via captopril infusion and
      vagotomy respectively. The sympathetic nervous system activity and its effect on
      baroreflex response were estimated by combined captopril infusion and vagotomy.
      There was elevation of mean arterial pressure (MAP) in salt-loaded rats (SR)
      relative to controls (NR) (140.5 +/- 2.18 vs 98.0 +/- 1.38 mmHg) without any
      significant effect on heart rate (HR) (406 +/- 8.58 vs 428 +/- 11.20 beats/min).
      Calcium supplement abolished the rise in MAP of salt-loaded-calcium-fed rats
      (SCaR) (102.8 +/- 2.30 mmHg) but led to reduction in their HR (389 +/- 10.21
      beats/ min) relative to control. Renin-angiotensin system inhibition led to fall
      in MAP in all groups of rats with the greatest reduction observed in SR.
      Inhibition of parasympathetic effects resulted in elevation of MAP in all
      thegroups. with SCaR and CaR having the highest rise. SR and SCaR had higher
      sympathetic activity than NR and CaR. Bilateral carotid occlusion test showed
      decrease baroreflex sensitivity in SR compared with NR while those of SCaR were
      enhanced without significantly affecting CaR. Also, there was enhanced baroreflex
      response (BRR) due to renin-angiotensin system inhibition in NR and SR while it
      was significantly reduced in SCaR but none in CaR. However, there was reduced BRR
      to parasympathetic inhibition in experimental groups except in CaR. Unmodified
      sympathetic activity resulted in enhanced BRR in all the groups. The results of
      the present study suggests that renin-angiotensin and autonomic nervous systems
      are impaired by dietary salt-loading, while prevention of salt-hypertension by
      calcium supplement is through modulation of these actions.

PMID- 17209325
TI  - Non-traumatic paraplegia in Nigerian children presenting at the University
      College Hospital, Ibadan.
AB  - A review of the presentation, management and outcome in all children presenting
      with non-traumatic paraplegia managed by the paediatric neurology team at the
      University College Hospital Ibadan, Nigeria from June 1989 to May 2004 is
      presented. Of the 110 patients, there were 54 males and 56 females giving a M:F
      ratio of 1:1. The mean age of the group was 5.3 (SD = 3.1) years, with a range
      from 9 months to 11 years. Infections and infectious processes caused the
      paraplegia in 102 (92.7%) of the cases with poliomyelitis and tuberculosis (TB)
      of the spine accounting for 88 (80%) of cases. The study period was divided into
      three 5 year periods. While poliomyelitis was the commonest cause of paraplegia
      (60%) in the first 5 years: TB spine was responsible for most cases (40%) in the
      last 5-year period of the study. There was a significant reduction in the total
      number of cases seen when the initial 5-year period was compared with the last
      (45 and 26 respectively, P = 0.001). Overall mortality among the 110 admitted
      patients was 7.2% being highest (50%) in malignant disorders and none was
      recorded in TB spine. Prognosis for eventual ability to walk was best in cases of
      TB spine where 37 of the 39 patients (95%) were ambulant by discharge after 60
      days of anti-TB treatment. The 2 non-ambulant patients eventually walked within 3
      months of discharge while on maintenance treatment for TB. Only 2 of the 51 non
      ambulant patients obtained wheelchairs at discharge. The implications of
      inadequate facilities for investigation and treatment as well as the lack of
      financial and social support for the families of affected children are discussed.

PMID- 17209326
TI  - Interspecialty referrals: evaluation of quality and pattern of referral letters
      to an oral and maxillofacial surgery clinic.
AB  - Referral letters are the most desirable means of communication between medical
      practitioners in patients' management, however many studies have indicated that
      this form of communication is often lacking in essential information necessary
      for prompt treatment. This study sets out primarily to evaluate the quality and
      secondarily pattern of referrals from other specialties within the University
      College Hospital, Ibadan, Nigeria, to the department of Oral and Maxillofacial
      surgery of the same institution. The information sought for in each letter were
      patient's name, age, sex: is the letter dated or not, referring department,
      history ofcomplaint, management already instituted, reason for the referral, name
      and the signature of the referring doctor. Each of these ten items was scored I
      when present and 0 when absent. Thus, a maximum score of 10 was recorded when all
      items were present. Referrals were graded into grade A-D. A being referrals with
      the maximum score of 10, B: scores of 7-9, C: scores of 4-6, D: scores of 0-3.
      There were only 9 grade A letters accounting for 3% of the total. Majority of the
      letters, 201 (77%) were of grade B while the remaining 52 (20%) were of grade C.
      The accident and emergency unit provided most of the letters i.e. 176 accounting
      for 67.7%. Plastic surgery and Accident/ Emergency units individually produced 3
      out of the 9 grade A letters, however, no statistically significant association
      was found between specialty units and grades of letters.

PMID- 17209327
TI  - Postdural puncture headache: a cross-sectional study of incidence and severity in
      a new obstetric anaesthesia unit.
AB  - Postdural puncture headache remains a major complication of subarachnoid
      anaesthesia that bothers the anaesthetist and the young mother. Identification of
      factors that may affect PDPH after caesarean section under subarachnoid
      anaesthesia could be critical to policy formulation in an emerging obstetric
      anaesthesia unit. All patients who had caesarean section under subarachnoid
      anaesthesia were evaluated in a cross-sectional manner. Only patients in whom 25G
      Quincke needles were employed for lumbar puncture were recruited for analysis.
      Patients who met criteria for postdural puncture headache were interviewed on
      postoperative day 3. The PDPH was further characterized to establish the time of
      onset, location of headache, limitation of activity of daily living, and methods
      of management. A total of 119 patients had lumbar puncture for spinal
      anaesthesia. Spinal anaesthesia was successful in 112 patients, inadequate in 6
      patients and failed in one. Twenty-seven patients (22.7%) developed PDPH. There
      was no difference in the demographic features in the patients who developed PDPH
      and those without headache. Clinical variables like site and number of attempts
      at dural puncture (p = 0.82. Chi-square test), traumatic attempts. parasthesia
      and volume of bupivacaine were not found to be determinants of PDPH. Successful
      dural puncture was achieved on first attempt in 42.0% (n = 47) of the patients.
      The PDPH was mainly occipital for most of the women, starting on postoperative
      day 2 and relieved with liberal fluids and paracetamol. Maternal experience of
      their caesarean section with spinal anaesthesia was satisfactory in 77.8% (n =
      21) of patients and 63% (n = 17) would recommend the technique to other women.

PMID- 17209328
TI  - Analysis of diurnal variation of lymphocyte subsets in healthy subjects in the
      Caribbean, and its implication in HIV monitoring and treatment.
AB  - Absolute values of the lymphocyte subsets are known to be influenced by various
      biological factors. We set out to determine if diurnal variations in lymphocyte
      subsets occur in our population. A prospective study was done on 25 randomly
      chosen healthy subjects. Persons were enrolled for the early morning to mid
      afternoon study i.e. 8:30, 12:30 and 15:30. In a second study, samples were
      collected at hourly intervals from 08:30 to 12:30. The EDTA samples were analyzed
      for lymphocyte subsets by flowcytomery. In the first study, the results have
      shown that there was a progressive increase in CD4 cell count throughout the day,
      while CD8 and CD19 cell counts increased between 08:30am and mid-day and then
      there was no further change between midday and mid afternoon. CD56 was uniform
      throughout the whole day. As most clinics and venesections take place in the
      morning, the aim of the second part of the study was to focus on the nature of
      the changes observed in the morning to midday phase. The results have shown that
      there were no significant changes in the lymphocyte subset counts before 11:30,
      thereafter there was a progressive increase in all of the lymphocyte subsets
      between 11:30 and 12:30 except for the CD56 cell count. This study has shown that
      diurnal rhythms influence the lymphocyte subsets in a normal population. This may
      have major implications in the use of CD4 subset analysis in the management of
      HIV infected persons as an indicator for initiation of treatment. In our setting.
      pending the results of diurnal variation studies on PLWHA, we have set the latest
      blood collection time at 11:30 am.

PMID- 17209329
TI  - International training in medical education--the FAIMER institute 2002 fellowship
      experience.
AB  - The concept of Medical Education as a specific discipline has advanced
      significantly. The Foundation for Advancement of International Medical Education
      and Research (FAIMER), Philadelphia, USA was formed in the year 2000 to
      disseminate the concept to medical schools worldwide. FAIMER Institutes are 2
      year long fellowship programs that were developed in 2001 to teach education
      methods and leadership skills to middle and senior level academicians from
      medical institutions in the developing world. In addition, the Institute fellows
      also carry out a curriculum innovation project in their institutions, in the
      interim period between two U.S. based workshops. This paper describes the
      experience of the authors and their co-fellows who participated in the 2002
      FAIMER Institute and highlights the main learning points of the course.

PMID- 17209330
TI  - Prevalence of HIV infection in school based and other young donors during the
      2002 and 2003 period.
AB  - The majority of donor blood in Zimbabwe comes from school-based donors. Zimbabwe
      has one of the highest HIV prevalences in the world and the age at which the
      infection is acquired is decreasing. This is a serious threat to the safety of
      blood supply. The prevalence of HIV has been low among the youth the majority of
      whom are still going to school and between the ages of sixteen and nineteen
      years. However, due to the changing socio-economic environment, sexual
      behavioural patterns have also changed. It is now necessary to evaluate these
      changes in order to guarantee safe blood transfusion. To determine the prevalence
      of HIV among adolescent donors during the period between 2002 and 2003. Cross
      sectional retrospective study, National Blood Transfusion Service (NBTS). All
      school based donors and others between 16 and 19 years of age. The number of
      donors who were HIV positive in this age group. Data on donors was collected from
      computer files at the National Blood Transfusion Service (NBTS) Information
      Technology (IT) department. Prevalence of HIV was determined and categorised
      according to gender, age and the type of school the donor attended. The
      prevalence of HIV in 2002 and 2003 were 0.48% and 0.38%, respectively. Sixty-six
      per cent (66%) of HIV positive donors had donated for the first time. The
      prevalence in both periods was much higher in female donors than male donors. In
      2002 males and females had prevalence of 0.28% and 0.66%, respectively. In 2003
      males and females had prevalence of 0.18% and 0.55%, respectively. The overall
      highest prevalence (0.90%) was found between the 16-19 year age group who were
      not going to school (others). In 2002 female day schools had the highest (0.87%).
      The lowest prevalence (0%) was found in male boarding schools. In 2003 the
      highest prevalence (1.61%) was found in the 16-19 year age group who were not
      going to school (others). The lowest prevalence (0) in the same year was found in
      male boarding scholars. It can be concluded that the majority of HIV positive
      school based donors are first time donors. Female scholars and those of the same
      age group who are not going to school have the highest risk of donating HIV
      positive blood than male donors. The prevalence of HIV in adolescent blood donors
      decreased with age. It is recommended that active donor recruitment should be in
      favour of the low prevalence groups.

PMID- 17209331
TI  - Dose-dependent changes in some haematological parameters during short-term
      administration of Hibiscus sabdariffa Calyx aqueous extract (Zobo) in Wistar
      albino rats.
AB  - The extract of Hibiscus Sabdariffa L. (MALVACEAE) is popularly consumed and
      assumed to have haematological benefits, but no scientific investigations are
      known in the literature to have been conducted to corroborate this claim. The
      present study was therefore conducted to evaluate the effects of Hibiscus
      Sabdariffa L. Calyx extract on some haematological parameters (Haemoglobin,
      haematocrit, total white blood cells and differentials) in rats, with a view to
      determining its medicinal usefulness in the treatment of anaemia. Proximate
      analysis on dry matter basis, and mineral clement analysis were carried out on
      dried calyx of Hibiscus Sabdariffa L. Different doses of aqueous extract of
      Hibiscus Sabdariffa L calyx extract (200 - 1000 mg/ kg body wt.) were
      administered orally by intra Ocsophageal cannulation to four groups of six
      animals (rats) per group for 14 days. Venous blood samples were collected from
      each animal in all the groups including the control group on days 0 and 14 of the
      experiment for haematological investigations. Paired stat analysis of day 0 and
      day 14 results was done for each group using student's T-test. Proximate and
      mineral analysis of dry calyx confirmed the presence of some nutrients, e.g.
      protein, mineral elements (potassium) and Vitamin C in the calyx. After 14 days
      of the extract administration, significant elevations were observed in
      haematocrit (P = 0.03) and haemoglobin (P = 0.004) in the groups of animals given
      doses of 200 mg and 400 mg per kg (P < 0.05) while the groups given high doses
      revealed significant reductions (P 0.031) in the haematocrit but not in
      haemoglobin. This study suggests that, aqueous extract of Hibiscus Sabdariffa L.
      calyx used in this experiment had beneficial effects on the red cells at low
      doses (200 mg-400 mg/kg) which may not be sustained at higher doses. However, the
      long-term effects and the possible mechanism (s) of action of the extract should
      be studied before a recommendation could be made.

PMID- 17209332
TI  - Comparative determination of halofantrine tablets by titrimetry,
      spectrophotometry and liquid chromatography.
AB  - Comparative determination of halofantrine tablets by titrimetry, ultraviolet
      spectrophotometry and liquid chromatography (LC) is described. Non-aqueous
      titrimetry on halofantrine hydrochloride tablets was carried out using glacial
      acetic acid as solvent, perchloric acid as titrant and crystal violet as
      indicator. Simultaneous potentiometric monitoring of end point delineated an
      exact color shade of indicator at the end point. Direct measurement of methanol
      solution, at 254 nm, was adopted for UV spectrophotometric method while reversed
      phase liquid chromatographic (LC) method employed a C8 column (4.6 mm x 25 cm)
      with mobile phase consisting of methanol / 0.05 M NaH2PO4 (76:24, v/v) containing
      55 mmol/L perchloric acid (pH 3.4) at a flow rate of 1 ml / min. The three
      methods gave precise and accurate results. Mean percentage recovery were obtained
      respectively as 100.73 +/- 0.41, 100.36 +/- 0.79 and 99.93 +/- 3.74% while
      coefficient of variation were 0.41, 1.36 and 3.74% for non-aqueous. UV
      spectrophotometry and LC. The three methods were successfully applied to analysis
      of halofantrine tablets (Halfan) and showed no statistically significant
      difference in accuracy (P > 0.05, ANOVA). Validated assay methods for
      halofantrine tablets have been developed. The titrimetric and spectrophotometric
      methods are of equivalent accuracy with the liquid chromatographic method and
      could be used for routine quality control of halofantrine tablets where LC method
      is not readily available.

PMID- 17209333
TI  - Pre-hospital treatment of febrile illness in children attending the General
      Outpatients Clinic, University College Hospital, Ibadan, Nigeria.
AB  - Many childhood febrile illnesses are treated at home prior to presentation. This
      study gathered information on treatment practices of caregivers for febrile
      illnesses in an urban area. A Cross sectional survey of consenting guardians of
      535 consecutive febrile children under 10 years presenting at General
      Outpatients' (GOP) Clinic. University College Hospital. Ibadan was carried out.
      Thick blood smears were examined for malaria parasite. The mean (SD) age of the
      febrile children was 3.2 (2.8) years. Nineteen (17.5%) children were brought
      within 24 hours of noticing fever. Malaria was presumed to be the diagnosis by
      217 (40.6%) respondents: 247 (46.2%) did not know the cause of fever. Most. 469
      (87.7%) respondents gave drugs bought from chemists/pharmacy shops before
      presentation at the GOP. Paracetamol 1380 (81.0%)] and chloroquine [171 (36.5%)]
      were the most commonly used drugs. Twenty-six (15.2%) respondents used
      chloroquine correctly. One hundred and ninety-nine of 476 children (41.8%) were
      smear positive and 88 of 191 (46.1%) children whose guardians presumed malaria
      had parasites. This study reiterates the fact that majority of childhood febrile
      illnesses are first treated at home. It underscores the need to empower
      caregivers by appropriate education on knowledge, attitude and practice of the
      management including home management of malaria.

PMID- 17209334
TI  - An audit of medical record-keeping in maxillofacial surgery at the University
      College Hospital, Ibadan using the CRABEL Scoring system.
AB  - Standard medical note keeping is an important aspect of patient management, and
      the importance of completeness of patients' records cannot be overemphasized,
      especially for the purpose of auditing, research, and medico-legal reasons. It is
      also an integral part of a good medical practice. However gross inadequacies are
      often noted. This may be partly due to the fact that until the recent past, cases
      of medical and professional negligence were uncommon in our environment. This
      audit exercise was embarked upon to assess the standard in the department using
      the CRABLE Scoring system with a view to standardizing and improving our
      practice. The result showed that the subsequent entry part of the medical notes
      assessed was marginally the best with a score of 66.5%, followed by initial entry
      which scored 65.3%, while consent had a score of 57.8%. The worst aspect of the
      notes was the discharge summary with a mean score of 29%. A total mean score of
      61.6% was achieved. Despite the limitations of the CRABEL Score such as the
      subjectivity of the assessment of the legibility of entries under subsequent
      entries, and perhaps the need to adapt it to our local and peculiar environment.
      it is useful as a regular auditing mechanism to improve medical keeping.

PMID- 17209335
TI  - Orofacial lesions in 126 newly diagnosed HIV/AIDS patients seen at the University
      College Hospital, Ibadan.
AB  - Human immune deficiency virus (HIV) infection is one of the most devastating
      infection in modern times. Oral manifestations of HIV infection occur in
      approximately 30-80% of patients infected with this virus and the factors, which
      predispose to these lesions include: CD4 count less than 200 cells/mm, viral
      load, xerostomia, poor oral hygiene and smoking. These manifestations have
      subsequently become important entry criteria for: clinical trials of various
      therapeutic regimes, prophylaxis of HIV related opportunistic infections, anti
      retroviral trials and vaccine studies. Over a six month period, all newly
      diagnosed HIV/AIDS patients attending the Special Treatment Clinic at the
      Haematology Department of the University College Hospital, Ibadan, Nigeria were
      recruited into this study before anti-retroviral therapy was commenced. As part
      of the general physical examination of these patients, a thorough orofacial
      evaluation was also carried out and the findings were documented. The most
      prevalent orofacial lesions were candidiasis, xerostomia, melanotic
      hyperpigmentation and herpetic ulcer among others. The aim of this study was to
      evaluate the pattern of oral lesions found in patients who were newly diagnosed
      as having HIV infection prior to commencement of anti-retroviral drugs and relate
      these lesions to the age, sex and occupation of the patients. These findings may
      suggest the likelihood that there is a pattern of oral manifestation of HIV
      infection.

PMID- 17209336
TI  - Spontaneous liver rupture in pre-eclampsia.
AB  - Spontaneous liver rupture is a rare complication of pre-eclampsia. A booked, 30
      year old woman with pre-eclampsia and twin gestation developed severe abdominal
      pains 10 hours after a supervised, vaginal delivery. On examination she was in
      hypovolemic shock with abdominal distension from hemoperitoneum. Uterine rupture
      was suspected and she had a laparotomy after resuscitation. But at surgery the
      uterus was intact and instead liver rupture was found which was managed by
      omental packing after evacuating the clots. Postoperatively, the patient
      developed acute renal failure that responded well to treatment. The mother and
      her babies were discharged in good health after 15 days of multidisciplinary
      management.

PMID- 17209337
TI  - [Long-term results of peripheral vascular injuries in patients' limbs following
      reconstructive surgical procedures and influence on the quality of life].
AB  - Major vascular injuries in extremities are rare and constitute problems for
      surgeons and their sequelae strongly influence remote future of the patients. The
      aim of study is to evaluate surgical treatment of vascular injuries in
      extremities and some aspects of quality of life. Since 1983 until 2002 sixty four
      patients with vascular limbs injuries were treated in the department. Remote
      evaluation has been performed in 33 persons. Severity of limb injuries was
      measured by Mangled Extremity Severity Score (MESS). In 20 patients (60.6%) very
      good and good recent results were obtained, satisfactory in 24.2% and bad results
      in 15.2% persons. Evaluation of functional status has been made by means of
      locomotion test and Jebsen-Taylor's test, social approval questionnaire,
      depression Beck's scale, the scale of hypochondria and by an original
      questionnaire to evaluate the quality of life. As considerable interdependence
      has been found between the functional status and the following factors: injury
      severity expressed in MESS (p < 0.01), clinic reception procedure (p < 0.001),
      ischemia time (p < 0.01), coincidence of other injuries (fractures and
      dislocations, muscle, tendon and nerve lesions) (p < 0.01), limb amputation (p <
      0.01). Hand function significantly influences the quality of life. Patients who
      were in shock after trauma in the remote assessment showed susceptibility to the
      lowered mood and depression (p < 0.05). Quality of life is strongly connected
      with the features of personality, correlating mainly with the mood and tendencies
      of concentration upon somatic symptoms. Function of the hand influences strongly
      the quality of life. Amputated patients may in spite of their crippling
      limitations are able to adapt to everyday life.

PMID- 17209338
TI  - [The plasma levels of orexigenic peptides and human platelets phospholipase D
      activity in anorexia nervosa patients].
AB  - Ghrelin, orexins A and B (OXA, OXB) are neuropeptides engaged in the regulation
      of energy balance stimulating appetite and feeding. Disturbances in their
      activity are proposed to be involved in pathomechanism of eating disorders,
      particularly in anorexia nervosa (AN). The intracellular mechanism of the
      peptides action remains unclear. It is considered whether the orexigenic peptides
      may act through second messengers related to phospholipase D (PLD). The aim of
      the study was to find a hypothetical relation between ghrelin, OXA and OXB levels
      and human platelets PLD activity. MATERIAL AND METHODS: 25 AN females and 20
      healthy controls (mean age 17.6 and 18.6, mean BMI 15.03 and 21.41 kg/m(2),
      respectively) were examined. OXA and OXB plasma levels and total ghrelin plasma
      level was determinated with RIA. PLD activity in homogenized blood platelets was
      assessed with modified fluorometric method. All values are presented as the mean
      values. The data were analyzed using Student-t test, non-parametric U-Mann
      Whitney test and Spearman correlation. The p < 0.05 was accepted as the level of
      significance. RESULTS: There is a correlation between analyzed neuropeptides and
      PLD in AN patients. CONCLUSION: In AN patients it is not possible to exclude
      influence orexins and ghrelin on platelet PLD activity.

PMID- 17209339
TI  - [EEG examination in patients with purulent, bacterial meningoencephalitis-
      literature review and own observations].
AB  - The study presents the literature review on EEG examination in purulent,
      bacterial meningoencephalitis as well as own observations carried out in 42
      patients with this neuroinfection treated in I Department of Infectious Diseases
      of Medical University of Silesia in Bytom between 1989-2001. In 19 patients the
      result of the first examination was abnormal and the degree of EEG patterns
      pathology correlated with the severity of their clinical condition. Abnormal
      electroencephalogram was also noted in 7 cases in the control examination. Two of
      this group of patients died and in two cases pathological EEG patterns preceded
      epileptic seizures during further hospitalization. Besides, the conversion of
      normal at the beginning into abnormal EEG patterns was found in cases of
      purulent, bacterial meningoencephalitis various complications, e.g. brain
      abscess. The obtained results indicate that EEG examination carried out in the
      acute phase of purulent, bacterial meningoencephalitis may be helpful in the
      estimation of severity of patient's clinical state. Performing of EEG examination
      in series during and after hospitalization may be useful for monitoring the
      course of the disease and prognosis of its outcome.

PMID- 17209340
TI  - [Influence of tobacco smoking and periodontitis on selected factors of oxidative
      stress].
AB  - The aim of the study was to estimate the influence of tobacco smoking and the
      clinical type of periodontitis on the chosen parameters of oxidative stress
      (superoxide anion generation on the ground of cytochrome c reduction in the whole
      blood, the concentration of autoantibodies for oxidized low-density lipoprotein
      in venous and gingival blood, the level of 8-hydroxy-2-deoxyguanosine (8-OHdG) as
      a marker of oxidative DNA damage in venous and gingival blood and the total
      antioxidant capacity in venous and gingival blood). MATERIAL AND METHODS: The
      study included 50 periodontitis patients (20 patients with generalized aggressive
      periodontitis - GAP and 30 patients with chronic periodontitis--CP), aged 28-55
      (the mean value 40.3). There were 28 females and 22 males. The control group
      consisted of 25 volunteers in good general health, aged 2-50 (the mean value
      37.8). There were 15 women in this group. In clinical examination ofperiodontium
      following indexes were included: plaque index (Silness and Loe), aproximal plaque
      index (Lange et al.), bleeding upon probing (Saxer and Muhlemann), pockets depth,
      the number of teeth. RESULTS: Significant influence of periodontal diagnosis on
      the level of 8-OHdG in gingival blood and total antioxidant capacity and also all
      analyzed clinical parameters was revealed. Significant total influence
      ofperiodontal diagnosis with tobacco smoking on total antioxidant capacity was
      also seen in venous blood (p = 0.004). CONCLUSIONS: 1) periodontal status
      impacted in significant way on the level of 8-OHdG in gingival blood and total
      antioxidant capacity in venous blood, 2) tobacco smoking and chronic
      periodontitis presence were connected with significantly decreasing levels of
      total antioxidant capacity in venous blood; this fact may be under importance in
      connection between periodontitis and atherosclerosis, 3) tobacco smoking was a
      significant factor in the progression ofperiodontitis (higher levels of plaque
      indexes, deeper periodontal pockets in nicotine addicted patients).

PMID- 17209341
TI  - [Schizencephaly--clinical and radiological presentation of pediatric patients].
AB  - Schizencephaly is a rare central nervous system malformation. The anomaly is
      characterized by uni- or bilateral clefts in the brain's cerebral hemispheres.
      There are 2 types of the anomaly distinguished: type I ("closed lips") if there
      are fused clefts in cerebral mantle and type II ("open lips") if the clefts are
      separated. The etiology of this malformation is not clear; both environmental
      (intrauterine cytomegaloviral infection) and genetic risk factors are considered
      (mutations in EMX2, Lhx2 genes). The aim of the study was the analysis of
      clinical presentation, neurodevelopment progress and seizures in children with
      schizencephaly. MATERIAL AND METHODS: We examined 9 children (4 girls, 5 boys) at
      the age of 3 months to 11 years at the time of schizencephaly diagnosis. The
      neuroimaging (computed tomography--CT or/and magnetic resonance imaging--MRI) was
      performed in all of the patients. We found bilateral schizencephaly in 7 patients
      and unilateral in 2 of them; in 5 patients the brain anomalies other than
      schizencephaly were found. Epileptic seizures are present in 7 patients; in 2 of
      them the epilepsy is drug resistant. The development is delayed in all our
      patients, in spite of one. CONCLUSIONS: Schizencephaly is a severe brain
      malformation almost always leading to developmental delay and epilepsy. We did
      not found the correlation between the type of anomaly and clinical course, the
      degree of developmental delay and the severity of epilepsy in our group patients.

PMID- 17209342
TI  - [Severity and rate of depression in obese patients after surgical treatment of
      obesity with Roux-en-Y gastric bypass procedure].
AB  - The goal of the study is to estimate emotional disorders rate in the group of
      morbidly obese patients. They were treated with with Roux--en-Y gastric bypass
      surgical procedure. MATERIAL AND METHODS: The study was carried out with Becks
      Depression Inventory (BDI) test among 10 females and 7 males. The test was
      performed three times in every patient-- once before the surgery and twice after
      the operation (in 2 and 6 month period). RESULTS: Before surgery we had 9
      patients with mild and 3 with moderate depression. After two months there were 4
      and after six only 3 patients with mild level of depression. Average results
      before surgery (in brackets 2 and 6 months after operation, respectively)--body
      mass: 135.1 (112.6 and 96.1) kg; BMI: 46 (38.2 and 32.7) kg/m2; BDI: 16.8 (9.7
      and 7.8) points. Hospitalization mean time: 10.5 day. CONCLUSION: The rate and
      level of the emotional disorders (depression) in morbidly obese patients
      following bariatric surgical procedure measured with Becks Depression Inventory
      is reduced when compared with pre-operative values. These results need further
      research.

PMID- 17209343
TI  - [Operative treatment of the intramedullary tumors with the methylprednisolone
      usage--preliminary report].
AB  - The aim of the study was to assess the intermediate results of the intramedullary
      tumors treatment with neuroprotection including the methyvlprednisolone (MP)
      usage. MATERIAL AND METHOD: In the 1995-2003 period 33 patients with
      intramedullary tumors were operated on in Department of Neurosurgery in
      Sosnowiec. They were 10 females and 23 males in the age range of 11-61 years.
      Neuroprotection of the spinal cord in the course of treatment included:
      determining operational tactics on the basis of magnetic resonance imaging (MRI)
      performed in three planes, using MP according to NASCIS II and in maintenance
      dose in the 2-7 day after the operation, SSEP monitoring, myelotomy in the form
      of anatomical preparation of the posterior longitudinal fissure, sparing big
      transverse branches of the vasocorona of the posterior column, debulking of the
      tumor with an ultrasonic aspirator or CO2 laser, closure of the spinal cord after
      the removal of the tumor with pial sutures and sutures of the arachnoidea.
      RESULTS: Among the operated tumors 16 had a clear border, the remaining ones were
      14 astrocytomas of varying malignancy and infiltration of the white matter of the
      spinal cord and 3 lipomas. Control MRI revealed a total removal of the lesion in
      23 patients (70%), gross total removal in 7 patients (21%) partial removal in
      three patients (9%). The postoperative condition of the patients 2-3 weeks after
      the operation showed improvement in 12 cases (37%), no significant changes in 10
      cases (30%) and deterioration in 11 cases (33%). CONCLUSION: Appropriate
      operative tactics together with the use of the MP make the acceptable morbidity
      rate after radical removal of intramedullary tumors .

PMID- 17209344
TI  - [Colposcopy of abnormal transformation zone].
AB  - The aim of the study was the determination of colposcopic images of the atypical
      transformation zone and the estimation of their relationship with cervical
      intraepithelial neoplasia. MATERIAL AND METHODS: 8700 women hospitalized in the
      Department of Gynaecology and Gynaecologic Oncology of the Municipal Hospital in
      Kielce between October 1996 and March 2003 were included in this study. In every
      investigated women the gynaecological examination, PAP smear, vaginal biocenosis,
      image colposcopy and histological examination were performed. Colposcopic images
      underwent computer analysis. Patients were divided into two groups. Behind the
      criterion of the division one accepted the occurrence (group 1) or the lack (the
      group II) cervical intraepithelial neoplasia in the histological examination.
      RESULTS: Atypical transformation zone occurred in 3.8% of investigated women. The
      statistical analysis showed the lack of the correlation between occurrence of
      flat punctation pattern and negative iodine uptake in women with the atypical
      transformation zone. Acetowhite epithelium, very white or gray opaque epithelium,
      flat mosaic, coarse mosaic, flat and coarse leukoplakia, coarse punctation and
      atypical vessels correlated statistically (p < 0.05) with the atypical
      transformation zone. CONCLUSIONS: Acetowhite, very white or gray opaque
      epithelium, coarse punctation, flat mosaic, coarse mosaic, flat and coarse
      leukoplakia, coarse punctation, atypical vessels are the characteristic
      colposcopy images of the transformation zone. There is a correlation between
      acetowhite epithelium and flat leukoplakia and CIN 1. Coarse punctation, coarse
      mosaic and coarse leukoplakia correlate with the presence of CIN 3. Flat
      punctation and negative iodine uptake are not characteristic colposcopy images of
      the atypical transformation zone.

PMID- 17209345
TI  - [Erythromycin improves quality of endoscopy for acute upper gastrointestinal
      bleeding].
AB  - Twenty four patients with acute upper gastrointestinal bleeding undergoing
      endoscopy were assessed. Thirteen received erythromycin before the examination
      and 11 did not. The cleansing effect was bad in 2/6, satisfactory in 4/3 and good
      in 7/2 patients (erythromycin/non erythromycin group respectively). The need for
      repeat endoscopy was in 3 and 8 patients respectively. In conclusion erythromycin
      given before endoscopy improves quality of endoscopic examination in patients
      with upper gastrointestinal bleeding.

PMID- 17209346
TI  - [Socio-economic factors of 1991-2000 Kalisz pulmonary tuberculosis (ptb)
      incidences appraisal].
AB  - An appraisal of socio-economic factors that might have influenced the number of
      pulmonary tuberculosis (PTB) incidences in Kalisz, i.e. an average size town, was
      performed. MATERIAL AND METHODS: The study concerned overall 376 PTB cases (265
      men and 111 women) reported in 1991-2000. RESULTS: Out of the patients subject to
      the study 50.8% were single. 26.9% produced elementary education degrees, 56.6%
      had graduated from vocational schools, 10.9% had attended secondary schools, and
      5.6% had completed higher education. 25.5% were employed on terms of employment.
      78.1% were labour with permanent income. 37.2% were pensioners. 10.4% were
      receiving state-subsidized living wages, 3.7% were obtaining social wages. 2.7%
      were supported by their parents. 20.5% claimed no permanent income. 12.0% were
      dwelling in one-room flats, 61.7% in two- or three-room ones, and 22.6% in four
      room or even bigger apartments. 3.7% were homeless. 75.0% were cigarette smokers,
      and 21.0% were abusing alcohol. 2.7% did not own any housing, were smokers and
      were abusing alcohol. Cigarette smoking, other (apart from terms of employment)
      maintenance source and vocational education degree were typical of majority of
      the subjects (75.0 - 56.6%). CONCLUSIONS: The factors that had influenced the
      higher number of PTB cases among men than women were: simultaneous alcohol abuse,
      cigarette smoking (M : F 78,0) and homelessness among men only. One-room dwelling
      (M : F 8,0), other maintenance sources, i.e. the dole (M : F 5,5), no permanent
      income (M : F 5,4), social wages (M : F 3,4) and vocational education (M : F 4,0)
      could have proved equally influential.

PMID- 17209347
TI  - [Twelve-month outcome of 658 patients with acute coronary syndrome without ST
      segment elevation assigned to early invasive strategy].
AB  - We aimed at assessing the frequency of death, myocardial infarction, unstable
      angina, repeat revascularization, cardiovascular hospitalisation during 12 months
      in patients assigned to early invasive strategy. MATERIAL AND METHOD: We analysed
      658 consecutive patients with acute coronary syndrome (ACS) without ST-segment
      elevation hospitalized between January 2000 and February 2003. Patients had to
      fulfill the following criteria: 1) rest angina within 24 hours prior to
      admission, 2) at least one of the following: ST-segment depression (> or = 0,05
      mV), transient (< 20 min) ST-segment elevation (> or = 0,05 mV), T-wave inversion
      (> or = 1 mV) in at least 2 contiguous leads, positive serum cardiac markers.
      RESULTS: All patients underwent coronary angiography followed by PCI
      (percutaneous coronary interventions) in 71.8% of patients. 18.2% were assigned
      to CABG (coronary artery bypass graft) and 8.7% of patients were treated
      conservatively. 1.3% of patients underwent PCI followed by an elective CABG
      surgery. In-hospital mortality rate was.,3%. 3.3% patients died after hospital
      discharge. The frequency of myocardial infarction, unstable angina and repeat PCI
      at 12 months was 2.1%, 16.8% and 11.5% respectively. The rate of cardiovascular
      hospitalisation was 15.6%. Multivariate analysis identified two independent
      predictors ofdeath: diabetes mellitus (OR: 7.02, 95% CI: 1.5-13.8, p = 0.03) and
      heart failure (OR: 12.6, 95% CI: 2.86-16.6 p = 0.005). CONCLUSIONS: Early
      invasive strategy in analysed group yields good long-term outcomes with low rate
      of adverse ischemic events. Independent predictors of deaths were diabetes
      mellitus and heart failure.

PMID- 17209348
TI  - [Hand injuries in adolescents].
AB  - MATERIAL AND METHODS: Based on the materials of 134 adolescent patients (age 15
      19) with hand injuries treated in the II Department of Surgery of the
      Jagiellonian University between 1987-2000 results of treatment were described.
      The adolescents constituted 11.8% of all patients treated due to hand injuries.
      RESULTS: Home was the most common place of the accident (59 patients - 44.01%),
      and the most common mechanism of injury was cutting by the glass or another sharp
      tool (61 patients - 45.52%). The mild and moderate injuries predominated (112
      patients - 83.58%). 39 patients (29.10%) were treated after alcohol abuse;
      unfortunately. 35 patients (26.12%) were hospitalized from 1 to 24 days (av. 7.14
      days). Time to obtain complete recovery reached max. 270 days but av. 55.56 days.
      Various degree of the persistent limitation of the hand function were observed in
      65 patients (48.5%). Two of them (1.49%) got the disability pension and 8 (5.77%)
      had to change former job and activities. CONCLUSION: The time of the complete
      cure could be shorter and the extent of persistent post-traumatic impairment of
      the patients with the heavy hand injuries could be limited if they would be
      treated in the specialized centers for hand surgery.

PMID- 17209349
TI  - [Infection in neutropenic cancer patients--etiology, microbiological diagnostics,
      treatment].
AB  - Therapy of malignancies is often complicated by neutropenia, which increases the
      risk of severe and rapidly progressing infections caused by bacteria and fungi.
      The etiology of infections in the past few decades has shifted from gram-negative
      to gram-positive organisms. Nowadays the most important pathogens are: coagulase
      negative staphylococci, alpha-haemolyic streptococci, Staphylococcus aureus and
      among gram-negative bacteria: Escherichia coli, Klebsiella spp., Pseudomonas
      aeruginosa. Because the progress of infection in this group of patients can be
      rapid, empirical antibiotic therapy should be administrated at the onset of
      fever. Before starting therapy specimen for microbiological culture should be
      taken. There are many approaches to antibiotic empirical therapy but the most
      frequently used is the combination of broad-spectrum beta-lactams (cefiazidime,
      ceftpime, piperacillin/tazobactam, carbapenem) plus aminoglycoside or monotherapy
      using an extended spectrum beta-lactam.

PMID- 17209350
TI  - [Hyperammonemia type II as an example of urea cycle disorder].
AB  - Ornithine transcarbamylase deficiency is the most common inherited urea cycle
      disorder. Its clinical manifestations as lethargy, vomites, coma and cerebral
      edema are the effect of the higher concentration of the ammonia in plasma.
      Hyperammonemia, caused by mutation in ornithine transcarbamylase gene, is often
      considered as a reason of coma by pediatricians but skipped by internist,
      although it is the third reason of hepatic coma in adults. This article is the
      recapitulation of published studies and their implication on everyday clinical
      practice.

PMID- 17209351
TI  - [Neurotoxicity of cyclosporine].
AB  - Using cyclosporine as an immunosuppressive drug allowed increasing survival of
      grafts as well as patients. Despite this drug is being safely used for many
      years, it can cause complications. The most often complications are
      nefrotoxicity, hepatotoxicity, diabetes mellitus, arterial hypertension and
      neurotoxicity. The most often manifestation of neurotoxicity are tremor,
      leucoencephalopathia, headache and even seizures. Among risk factors we can
      enumerate arterial hypertetension, low cholesterol level, hypomagnesemia and
      previous cerebrovascular insufficiency.

PMID- 17209352
TI  - [Interventional radiology techniques in the treatment of Budd-Chiari syndrome].
AB  - Budd-Chiari syndrome (BCS) is rare clinical state characterized by the stenosis
      or complete obstruction of hepatic veins. Currently interventional radiology
      techniques are more frequently used as a single method of treatment or as a
      bridge to liver transplantation. This paper presents current interventional
      radiology techniques used in BCS treatment. Depending on etiology of BCS two
      major techniques are used: transjugular intrahepatic portocaval shunts (TIPS) or
      percutaneous angioplasties of stenosed hepatic veins. We also present selected
      cases of BCS diagnosed and treated in our Department in years 1999-2003.

PMID- 17209353
TI  - [How estrogens will surprise us again?].
AB  - Estrogens are pleiotropic hormones having an influence not only on reproductive
      system and sexual functions. These hormones are synthesized not only by ovaries,
      but also by glia in central nervous system (CNS) and Schwann cells in peripheral
      nervous system. Therefore they create microenvironment having a wide spectrum of
      effects such as neuroprotective and antiapoptotic or supporting neurogenesis and
      regeneration. Mechanisms of estrogens activity are both genomic and quick non
      genomic transmitted through second intracellular messengers. There is evidence
      for protective action of estrogens in neurodegenerative diseases and other
      diseases of CNS. Nevertheless there are still secrets in estrogens nature. This
      fact pushes us to ask more questions and continue scientific research to look for
      the answer.

PMID- 17209354
TI  - [Acute viral gastroenteritis in children].
AB  - The article presents common etiologic agents of viral gastroenteritis in
      children. The actual knowledge on molecular characteristics of rotaviruses,
      noroviruses, sapoviruses, astroviruses, and adenoviruses as well as their
      epidemiology in the world and Poland is reviewed. The authors emphasize the need
      of greater use of molecular procedures (RT-PCR) for detection the common
      serotypes of rotavirus and other viral agents of gastroenteritis in Polish
      children. Familiarity with molecular epidemiology of viruses and with their
      antigenic diversity allows to elaborate and apply the adequate vaccines as well
      as to initiate the prophylactic procedures.

PMID- 17209355
TI  - [Infections in the elderly. Part I. Etiology and pathogenesis].
AB  - An increase in the percentage of elderly subjects in the society has been
      observed in Poland and in the world from many years. Ageing is associated with an
      impaired functioning of many organs and systems, including the immune system,
      respiratory system and the urinary tract. Although circulating immune cell
      numbers and immunoglobulin levels are relatively unchanged, changes in cell
      activity (especially T-lymphocyte function, among others an increase in CD4+/CD8+
      ratio and increase in the proportion of memory cells with a concomitant decrease
      in naive T lymphocytes) cause a decline in both cell-mediated immunity and
      antibody response to immunogen. Age-associated changes in local defenses are also
      important: decreased functioning of respiratory system, ageing of the skin,
      atrophy of urinary tract, and decrease in gastric acidity. All of these
      impairments result in decreased resistance to infections. People over the age of
      65 are at increased risk of developing pneumonia, influenza and urinary tract
      infections. It presents not only a serious clinical problem but also
      epidemiological and social one.

PMID- 17209356
TI  - [Antimicrobial peptides].
AB  - For many years, attention has been focused on adaptive immunity as the main
      antimicrobial defense system. The discovery of antimicrobial peptides turned this
      point of view. In general, these peptides act on microorganisms directly by
      disrupting the structure of the microbial cytoplasmatic membranes and indirectly
      acting on immune system. This review provides an overview of some natural
      antimicrobial peptides and probability of their clinical usage.

PMID- 17209357
TI  - [Magnetic resonance imaging in the diagnosis of retrosternal anterior
      diaphragmatic hernia in an adult man].
AB  - The study presents a case report of a retrosternal anterior diaphragmatic hernia
      in a 46-year-old man presented with abdominal pain, nausea, dyspnoea and treated
      previously as for chronic pancreatitis. A strong suspicion of the diaphragmatic
      hernia was generated after chest radiograph. However, the exact diagnosis of the
      Morgagni hernia was established by magnetic resonance imaging. The hernia was
      repaired through thoracic incision. The postoperative course proved uneventful:
      the patient was discharged from the hospital 10 days after surgical intervention.

PMID- 17209358
TI  - [Diagnostic problems in case of primary central nervous system lymphoma].
AB  - The authors described a case of young patient with primary central nervous system
      lymphoma (PCNSL). Unspecific initial symptoms and clinical course, as well as
      neuroimaging findings caused many diagnostic difficulties. The diagnosis of PCNSL
      was finally established on the basis of stereotactic brain biopsy, after 18
      months of follow-up.

PMID- 17209359
TI  - [Platelet satellitism].
AB  - Platelet satellitism is an infrequent phenomenon of platelet adhesion to
      leucocytes. Twelve-month-old patient was hospitalized because of
      bronchopneumonia. In peripheral blood smear prepared from EDTA-anticoagulated
      blood sample taken from this patient platelet satellitism was observed. As time
      went by, a gradual, small decrease of platelet count was observed. Cytometric
      analysis showed the following proportions of platelet aggregates: with
      granulocytes--88,7%, with monocytes--5,0%, with lymphocytes--17,0%. In spite of
      using modern hematological analyzers still microscopic assessment of peripheral
      blood sample is necessary. Microscopic examination of blood smear is necessary
      not only to assess erythrocytes and leucocytes systems but also blood platelets.

PMID- 17209360
TI  - [Lance-Adams syndrome in patient with anoxic encephalopathy in the course of
      bronchial asthma].
AB  - Lance-Adams syndrome, described in 1963, is caused by anoxia of central nervous
      system, generally in the course of primary respiratory failure. It is
      characterized mainly by action myoclonus, associated cerebellar ataxia and very
      mild intellectual deficit. Occurrence of Lance-Adams syndrome is rare; about 100
      cases have been described yet. The authors present the case of Lance-Adams
      syndrome in 36-year-old woman with many years' bronchial asthma. Three times
      acute cardiopulmonary arrest appeared during status asthmaticus. After successful
      cardiopulmonary resuscitation action myoclonus developed with cerebellar
      syndrome, aphonia, dysphagia and generalized convulsive seizures of tonic-clonic
      type. Electroencephalography showed polyspikes and complex of polyspikes-slow
      wave, synchronized with myoclonus. CT of the brain was normal. Action myoclonus
      responded appropriately to sodium valproate. The authors indicate the importance
      of the correct diagnosis and proper treatment.

PMID- 17209361
TI  - [Marchiafava-Bignami disease].
AB  - Marchiafava-Bignami disease (MBD) is a rare central nervous system disorder of an
      unknown etiology strongly associated with alcoholism. MBD primarily affects the
      corpus callosum leading to confusion, dysarthria, seizures and frequently to
      death. About 250 cases of different races and nationalities, mostly alcoholics
      have been reported. We report a single-case study of a 43-year-old woman with the
      history of severe alcohol abuse, who demonstrated typical picture of Marchiafava
      Bignami disease (MBD) with fatal course. We reviewed the literature on cases of
      MBD.

PMID- 17209362
TI  - [Cecum mobility as a cause of ileus].
AB  - The authors present a rare case of ileus caused by unusual cecum mobility. The 31
      years old female patient was diagnosed ineffectively several times due to
      abdominal pain. The diagnostics, an attempt of a conservative treatment, along
      with surgical and postoperative treatment are discussed.

PMID- 17209363
TI  - [Intestinal tract endometriosis].
AB  - Pelvic endometriosis in 3-37% of cases involves the intestinal tract, mainly
      sigmoid colon and rectum. In clinical practice endometriosis of the intestinal
      tract is rarely diagnosed and usually after long-lasting symptoms. During 3 years
      we treated only 2 women with this disease and therefore we want to report this
      seldom disorder. One woman had been diagnosed as having had rectal endometriosis
      before she was admitted to the hospital and the other one was admitted because of
      complications after laparoscopic treatment of pelvic endometriosis. In spite of
      typical signs of intestinal tract endometriosis, the proper diagnosis was made
      after several years of symptoms in one woman and in the second female
      histopathology of removed sigmoid colon because of its lesion finally revealed
      endometriosis. Laparoscopy seems to be the best diagnostic method of intestinal
      endometriosis and its treatment is to remove the involved part of the bowel
      together with endometriotic foci and surrounding tissues. Cyclical intestinal
      endometriosis symptoms correlating with menstrual cycle should always draw our
      attention to this rare disorder.

PMID- 17209364
TI  - [Leukemoid reaction with uncommonly high leucocytosis in the course of serious
      infection].
AB  - We present a case of 51-year old female patient with gastrointestinal perforation
      and septic shock leading to leukemoid reaction with WBC 155 x 109/l. Leukemoid
      reaction in neoplasms and infections can mimic chronic myelogenous leukaemia and
      is an important diagnostic problem.

PMID- 17209365
TI  - [Unique massive recurrence liposarcoma of the retroperitoneum].
AB  - Liposarcoma constitutes a heterogeneous group of tumors which rarely arise from
      the retroperitoneal area. They are the single most common tumor in all sarcoma of
      the retroperitoneum space. Surgery plays a dominant role in the treatment of
      retroperitoneal liposarcoma. The histologic subtype and margin of resection are
      prognostic for survival in primary tumors. Local recurrences are the most
      frequent cause of failure of the surgery. We report the case of a patient with
      massive recurrences ofretroperitoneal liposarcoma. A 45 year-old male had low
      grade liposarcoma of the retroperitoneum which recurred 6 times within 10 years.
      The next retroperitoneal recurrence tumor excised weighted 25 kg in total. Seven
      months after resection the patient feels well. We conclude that aggressive
      surgery in recurrent tumors can produce prolonged survival in patients with low
      grade retroperitoneal liposarcoma.

PMID- 17209366
TI  - [The significance of electrocardiogram in the estimation of correct lead position
      in patients with permanent ventricular pacing].
AB  - Transvenous pacemaker lead malposition in the left ventricle is a rare
      complication of pacemaker implantation however, at the moment of diagnosis poses
      the serious therapeutic problem. The usual morphology for paced events
      originating from the right ventricle has a left bundle branch block pattern, but
      sometimes right bundle branch block (RBBB) configuration is identified. The
      report describes two cases of RBBB configuration in the electrocardiogram (ECG)
      after pacemaker implantation. Case 1 demonstrates a female with unintentional
      pacemaker lead placement in the left ventricle through patent foramen ovale. Lead
      malposition was diagnosed accidentally during echocardiographic study (ECHO), 6
      years after implantation. Case 2 concerns a man with a RBBB pacing configuration,
      but with correct pacemaker lead position in the right ventricle. Authors analyze
      these cases in connection with other publicized reports in order to find the safe
      algorithm for intraoperative estimation of correct pacemaker lead location. The
      following algorithm of procedures during pacemaker implantation is proposed to
      avoid the lead malposition in the left ventricle. First, obligatory perform 12
      lead ECG in pace mode during surgery or immediately after it. Second, in case of
      RBBB pattern in post implant ECG, make ECHO for precise lead position
      description.

PMID- 17209367
TI  - [Cell culture, tissue engineering and regenerative medicine. Part I].
AB  - Tissue engineering is an interdisciplinary field that applies the principles and
      methods of engineering and the cell culture toward the development of
      biomaterials that restore, maintain or improve tissue function. The amalgamation
      of engineering and medicine has interested many scientists for at last two
      hundred years. What was the goal of cell culture? First, for progress in life
      sciences achievement and subsequent for virology and toxicology development. In
      vitro studies are done because of many problems with carrying out animal
      experiments. In this work the authors present the attempts of physicians,
      anatomopathologists, embryologists and biologists which contributed to fast
      development of new area in medicine--tissue engineering.

PMID- 17209368
TI  - [Effects of ramets adjustment on Quercus liaotungensis growth and seed
      generation].
AB  - This paper studied the effects of different ramets adjustment measures on the
      growth and seed generation of Quercus liaotungensis shrub in the upper reach of
      Minjiang River. The results showed that artificially adjusting ramets number
      largely affected the growth of plant height and sexual reproduction of Q.
      liaotungensis. The adjustment had little effect on the basal diameter of remained
      ramets, but obviously affected their height if 2 or 3 ramets per shrub were
      remained. The number, total length, and total biomass of new branches of adjusted
      shrub had more increase than those of unadjusted one, especially for the shrub of
      remaining 2 ramets. In adjusted shrub, the number and total biomass of leaves
      increased obviously, and the leaf area decreased gradually with increasing number
      of remained ramets. The shrub with three remained ramets generated most seed,
      while natural shrub had the biggest weight of single seed.

PMID- 17209369
TI  - [Responses of Shenyang urban tree phrenology to climate warming].
AB  - By using statistic and linear regression methods, this paper studied the last 40
      years responses of Shenyang urban tree phenology to climate warming. The results
      showed that there was a significant correlation between the duration of tree
      dormancy and the mean air temperature in winter. Appropriate cold condition was
      beneficial to bud break, and a significant negative correlation was observed
      between the outset of sprouting and the mean air temperature in winter and early
      spring. Leaf expansion started 15 days after sprouting, which was mainly affected
      by the mean air temperature in spring but had no correlation with the temperature
      in winter. The air temperature within 20-80 days and especially 20-40 days before
      flowering had a significant effect on the outset of flowering, i. e. , an
      increasing temperature in spring could advance the outset of flowering. Both
      sprouting and leaf expansion were negatively correlated with cold index (CI) ,
      but no significant correlation was observed between the outset of flowering and
      CI. An increase of mean annual air temperature by 1 degree C would advance the
      outset of sprouting by 9 days, leaf expansion by 10 days, and outset of flowering
      by 5 days.

PMID- 17209370
TI  - [Canopy rainfall storage capacity of tropical seasonal rainforest and rubber
      plantation in Xishuangbanna].
AB  - Based on the 2003-2004 laboratory and field observation data, and with scaling-up
      method, this paper studied the canopy rainfall storage capacity of tropical
      seasonal rainforest and rubber plantation in Xishuangbanna. The results showed
      that the canopy rainfall storage capacity was 0.45-0.79 mm for tropical seasonal
      rainforest and 0.48-0.71 mm for rubber plantation, and that of the branch and
      bark accounted for >50 % of the total. For these two forests, the canopy rainfall
      storage capacity was much higher in foggy season (from November to February) and
      dry-hot season (from March to April) than in rainy season (from May to October),
      and the duration needed to reach water saturation was about 5 min for leaf, 2-3 h
      for bark, and 2. 5-4 h for branch. During the processes of wetting and air
      drying, leaf was easier while branch and bark were somewhat difficult to hold
      water and then be air-dried, suggesting that leaf played an important role in
      intercepting rainfall in short-duration rainfall events, while branch and bark
      could work much better in doing this in long-duration or high-intensity rainfall
      events. Compared with rubber plantation, tropical seasonal rainforest had a
      stronger rainfall-storage capacity due to its multi-layer structure of canopy and
      excellent water-holding performance.

PMID- 17209371
TI  - [Respiration rate of broadleaved Korean pine forest ecosystem in Changbai
      Mountains].
AB  - In this paper, the respiration rates of soil, foliage, and stem and branch in the
      broadleaved Korean pine forest ecosystem of Changbai Mountains were measured by
      Li-6400 CO2 analysis system in 2003, with the microclimate factors determined
      synchronously. The correlation models of ecosystem respiration with environmental
      factors were established, and the respiration rate of each component of the
      ecosystem was estimated based on the vegetation characteristics of the
      broadleaved Korean pine forest. The results showed that the annual total
      respiration rate of the ecosystem was 1602. 8 g C x m(-2), with a mean of (4.
      37+/-2. 98) micromol x m(-2) x s(-1) , and the respiration of soil, foliage, and
      stem and branch contributed about 63% , 21% , and 16% of the total, respectively.
      There was a significant correlation between system respiration and daily mean air
      and soil temperature, and about 87% and 95% of the ecosystem respiration could be
      explained by the air and soil temperature, respectively.

PMID- 17209372
TI  - [Genetic diversity of arbuscular mycorrhizal fungi associated with four Alnus
      species in Changbai Mountains: a nested PCR-rFLP analysis].
AB  - In this paper, the colonization of arbuscular mycorrhizal fungi (AMF) on the root
      samples of 4 Alnus species in Changbai Mountains was investigated by using nested
      PCR-RFLP technique, and the PCR results were tested by restriction endonuclease
      analysis method. The results revealed that the uncultured AMF had a high genetic
      diversity, and the colonization had a trend from promiscuity to specialization.
      The AMF from Alnus mandshuica showed the greatest specialization to the host, and
      Glomus was the dominant colonizer of A. mandshuica. The AMF from A. sibirica var.
      hirsuta, A. sibirica, and A. tinctoria showed promiscuity, and host had more
      significant effects on the colonization of AMF than altitude.

PMID- 17209373
TI  - [Anatomical and water physiological plasticity of Grewia biloba var. parviflora
      leaf and secondary xylem].
AB  - Based on the anatomical observations of leaf and secondary xylem as well as the
      measurements of leaf water physiological parameters, this paper studied the
      anatomical and water physiological plasticity of Grewia biloba var. parviflora
      growing in different succession stage communities. The results showed that G.
      biloba var. parviflora leaf was characterized by thin bifacial with thin cuticle
      and few stoma, indicating that it was mesophyte anatomically, while the secondary
      xylem had typical xeromorphic traits, such as short and thin vessel, high vessel
      frequency, low percentage single pores, and short fibers and rays. G. biloba var.
      parviflora had high plasticity in the anatomical structure and water
      physiological features of leaf and secondary xylem, and the plasticity index was
      in the order of secondary xylem anatomical structure (0. 24) > water
      physiological traits (0. 19) > leaf anatomical structure (0. 18). Compared with
      those growing in mixed forest and Platycladus orientalis forest, the individuals
      of G. biloba var. parviflora in shrub communities had the xeromorphic traits in
      the aspects of (1) their secondary xylem had shorter vessel elements, higher
      vessel frequency, less single porous percentage, lower rays, higher relative
      conductivity and lower vulnerability index, and (2) their leaf had lower water
      potential, lower water content and free water content, higher bound water
      content, high ratio of bound to free water content, and less specific leaf area.
      The phenotypic plasticity, both anatomical and physiological, made G. biloba var.
      parviflora tolerate to the drought at earlier succession stages and better adapt
      to the mesophytic condition at later stages, and consequently, become a widely
      distributed and dominant species in mixed forests.

PMID- 17209374
TI  - [Forest carbon storage and fuel carbon emission in Tanjiang River basin].
AB  - The investigation on the forest carbon storage and fuel carbon emission in
      Tanjiang River basin showed that since 1990, the forests in Tanjiang River basin
      acted as a carbon sink, and this action was increased with time and with economic
      development. The net carbon uptake by the forests was 1.0579 x 10 (7) t in 1990
      and 1.28061 x 10 (7) t in 2002, with an annual increment of 1.856 x 10(5) t,
      while the fuel carbon emission was 9. 508 x 10(5) t in 1990 and 1.8562 x 10(6) t
      in 2002, with an annual increment of 7.0 x 10(4) t. In 2003, the fuel carbon
      emission was up to 2.1968 x 10(6) t, 3.406 x 105 t more than that in 2002. In
      2002, the energy consumption per 10(4) yuan GDP in Tanjiang River basin was 2.21
      t standard coal, higher than the average consumption (1.81 t standard coal) in
      the Pearl River delta. If the fuel consumption decreased to the average level,
      the carbon emission in Tanjiang River basin would be reduced by 3.360 x 10(5) t,
      which was higher than the annual increment of forest net carbon uptake in the
      basin. From the viewpoint of net carbon uptake and emission in a basin, more
      attention should be paid to the relations between forest carbon sink and human
      activities.

PMID- 17209375
TI  - [Diurnal dynamics of photosynthetic and transpiration rates of alfalfa under dry
      farming and their relationships with environmental factors].
AB  - In this paper, the diurnal dynamics of photosynthetic rate (Pn) and transpiration
      rate ( Tr) of four years planted alfalfa under dry farming, as well as those of
      photosynthetic active radiation (PAR) , CO2 concentration in field ( Ca ) ,
      relative humidity (RH) and air temperature ( Ta) were measured, and the
      relationships between the diurnal dynamics of Pn, Tr and climatic factors were
      analyzed by correlation coefficient, path coefficient, and decision coefficient
      analyses. The results showed that T. had the greatest effect on the diurnal
      dynamics of Pn , while RH, PAR and C, affected P,, mainly through their acting on
      Ta PAR had the greatest effect on the diurnal changes of Tr, and RH, Ta and Ca
      affected Tr indirectly by acting on PAR. For the characteristics of
      photosynthesis and transpiration, PAR was the primary determining factor, and Ta
      was the main limiting factor.

PMID- 17209376
TI  - [Nitrogen and phosphorus removal from septage filtrate in a ryegrass hydroponic
      system].
AB  - With hydroponic method, this paper studied the ryegrass Lolium multiflorum growth
      and its N and P removal under the application of septage filtrate. The results
      showed that a medium application rate of septage filtrate gave the highest yield
      of L. multiflorum. The N and P removal in the ryegrass hydroponic system was
      increased with increasing application rate of septage filtrate, but the water
      quality was declined when super high volume of septage filtrate was added. The N
      and P uptake by L. multiflorum had no significant difference under medium, high,
      and super high application rate of septage filtrate, with the maximum uptake of N
      and P being 13.6 g x m(-2) and 3.17 g x m(-2) respectively. The removed
      proportion of N and P through ryegrass uptake declined w ith increasing septage
      filtrate application rate. Under the same total load, increasing the application
      frequency of septage filtrate could improve ryegrass yield, water quality, and
      nutrients removal. To select an appropriate application rate and frequency of
      septage filtrate was the key in improving the nutrients removal efficiency of
      ryegrass hydroponic system.

PMID- 17209377
TI  - [Nutrient leaching and acidification of Southern China coniferous forest red soil
      under stimulated N deposition].
AB  - In an eight months interval leaching experiment with soil column (10 cm in
      diameter and 60 cm in height) at 20 degrees C, this paper studied the effects of
      N deposition on the leaching losses of soil NO -, NH4+ , H+, Ca2+, Mg2+ , K+, and
      Na+ , and on soil acidification. Soil columns were taken from the coniferous
      forest experimental plot at the Red Soil Ecological Experiment Station of Chinese
      Academy of Sciences in Southern China, and the N deposition loads were 0, 7.8, 26
      and 52 mg N x month (-1) x column (-1) , respectively. The results indicated that
      the leaching losses of total exchangeable cations, Ca2+ , and Mg2+ increased with
      increasing N deposition loads, but K+ and Na+ were little affected. The
      proportion of net cations leaching loss (difference of cations in eluate and
      leachate) to total exchangeable cations was 13.9% , 18.6% , 31.8% and 57.9% under
      0, 7.8, 26 and 52 mg N x month (-1) column (-1) deposition loads, respectively,
      and that for exchangeable Ca2+ and Mg2+ was 19. 6%, 25.8% , 45. 3% and 84.8% ,
      and 4.4% , 6.1% , 10. 9% and 17.1% , respectively. The leaching losses of
      inorganic N, NO3- and H+ also increased with increasing N deposition loads.
      Topsoil pH decreased with increasing N deposition loads, being 3.85, 3.84, 3.80
      and 3.75 under 0, 7.8, 26 and 52 mg N x month (-1) x column(-1) N deposition
      loads, respectively. N deposition could increase the apparent mineralization rate
      of soil organic nitrogen, and accelerate the nutrient losses and acidification of
      coniferous forest red soil.

PMID- 17209378
TI  - [Effects of land use type on soil organic carbon, total nitrogen, and microbial
      biomass carbon and nitrogen contents in Karst region of South China].
AB  - A total of 721 surface (0-20 cm) soil samples were collected from the paddy
      field, upland, and woodland in the Karst region of Dacai, Huanjiang County,
      Guangxi Province, and the contents of their organic carbon (Oc ), total nitrogen
      (TN), microbial biomass carbon (Bc) , and microbial biomass nitrogen (BN) were
      determined. The results showed that the Oc and BN contents and soil pH value
      showed the trend of paddy field = woodland > upland, while TN and Bc contents had
      the trend of woodland > paddy field > upland. There was a significant positive
      correlation between Bc and Oc, and between B5 and TN. Soil microbial biomass C
      and N had rapid responses to the changes of land use type, which could be used as
      the sensitive biological indicators in evaluating soil quality and fertility in
      Karst region.

PMID- 17209379
TI  - [A comparison of water balance in small basins with different landscape pattern
      in the upper reaches of Minjiang River].
AB  - This paper studied the effects of landscape pattern (land cover types, altitude,
      slope, aspect, patch density and maximum patch index) on the elements of water
      balance (precipitation, evapotranspiration, and runoff) in two small basins
      (Zhenjiangguan River and Heishui River) in the upper reaches of Minjiang River
      during 1988 -2002. Based on the spatial distribution of mean annual precipitation
      and evapotranspiration as well as the mean annual runoff on different land cover
      (woodland, grassland and cropland) during 1988-2002, the relationships of
      landscape pattern with water balance was approached, and the results showed that
      in these two basins, the precipitation, evapotranspiration / precipitation ratio,
      and runoff / precipitation ratio had a greater difference with the altitude,
      slope, and aspect of woodland, and grassland had a similar hydrological effect as
      woodland. On the farmland of Heishui River basin, which was distributed in dry
      valley, evapotranspiration was much higher than precipitation. This abnormal
      water balance was caused by the arid valley climate in the upper reaches of
      Minjiang River but not the landscape pattern of farmland, being totally different
      with that in Zhenjiangguan River basin.

PMID- 17209380
TI  - [Use efficiency and fate of fertilizer N in tomato field of Nanjing suburb].
AB  - Field plot and micro-plot experiments were conducted to investigate the use
      efficiency (UE) , fate, and loss of chemical fertilizer N in tomato field of
      Nanjing suburb. The results showed that the application of chemical fertilizer N
      did not show any benefit to the tomato yield, due to the adequate N supply from
      native soil and organic manure amendment. The UE of fertilizer N calculated by
      difference method ranged from 14.5% to 22.5%. In micro-plot experiment, 16.6% -
      28.8% of applied urea 15N was recovered by the plant, and 34. 2% - 46.0% of it
      was lost. Applying fertilizer N increased the nitrate content in 0-100 cm soil
      layer, and 10% - 10.2% of urea 15N was leached to the depth below 40 cm at
      harvest time. N application increased the denitrification loss and N2O emission
      significantly, which occupied 5.50% - 6.01 % and 2. 62% - 4. 92% of the applied
      N, respectively. No ammonia volatilization was detected during the whole growth
      season. Reducing N application rate or applying coated urea could decrease the
      environmental risks of N application in vegetable fields, especially the risks
      from nitrate leaching and nitrification-denitrification loss.

PMID- 17209381
TI  - [Effects of P application on P concentrations in paddy soil and its surface
      water: a simulation test].
AB  - An anaerobic incubation test was conducted to study the effects of different P
      application rate on the P concentrations in paddy soil and its surface water. The
      results showed that soil available P (Olsen-P) decreased rapidly at the
      beginning, but approached to stable after 60 days of P application. Both Olsen-P
      and residual P increased with increasing P application rate, and Olsen-P had a
      positive correlation with P application rate, suggesting that the test soil had a
      strong P adsorption capacity. After P application, the total P (TP) in soil
      surface water increased rapidly, and then decreased slowly, showing that there
      was a P exchange between soil and its surface water. After 120 days of P
      application, there was an exponential relationship between soil surface water TP
      and P application. The TP in soil surface water increased rapidly when the P
      application rate was 400 - 800 kg x hm (-2) , and easy to be lost when the P
      application rate was higher than 800 kg x hm(-2). The simulation with split line
      model on the relationship between soil Olsen-P and soil surface water TP showed
      that the change point of soil Olsen-P, which induced a sharp increase of soil
      surface water TP concentration, was 82. 7 mg x kg( -l) , corresponding to a P
      application rate being about 712 x kg hm(-2). Soil Olsen-P could be a good
      indicator in forecasting the P loss from soil surface water.

PMID- 17209382
TI  - [Effects of short-term high temperature stress on flag leaf photosystem II
      functions of high-yielding wheat at late grain-filling stage].
AB  - By using fast OJIP chlorophyll a ( Chl a) fluorescence transients, this paper
      studied the effects of short-term high temperature stress on the flag leaf
      photosystem II (PS II ) functions of high-yielding winter wheat cultivar 01-35 at
      its late grain filling stage. The results showed that with the temperature raised
      from 37 degrees C to 43 degrees C , the extent and velocity of QA reduction
      enhanced gradually, being 23. 89% and 24. 09% higher at 43 degrees C than at room
      temperature, respectively, which suggested that the electron transport from QA to
      QB was inhibited. The electron acceptor pool of PS 1I including QA Q, and PQ at
      43 degreesC decreased to 47. 4% of that at room temperature, indicating its being
      damaged. The electron donor side of PS II was not damaged from 37 degrees C to 43
      degrees C. When temperature raised to 46 degrees C , the extent and velocity of
      QA reduction were 13. 95% and 20. 48% higher than those at room temperature,
      respectively, but decreased obviously, compared with those at 43 degrees C. In
      contrast, the electron acceptor pool of PS II at 46 degrees C had no obvious
      change, compared with that at 43 degrees C, indicating that the electron donor
      side of PS II at 46 TC was damaged. Comparing with cultivar Lumai 14, the light
      harvesting complex ( LHC U) of high-yielding wheat cultivar 01-35 could harvest
      more sun energy, and distributed more absorbed energy into electron transport,
      suggesting that the LHC II of cultivar 01-35 could endure a certain higher
      temperature, and maintain higher electron transport capacity.

PMID- 17209383
TI  - [Effects of different irrigation modes on biological characteristics and water
      use efficiency of paddy rice].
AB  - With hybrid rice cultivar Liangyou Peijiu as test material, this paper studied
      its biological characteristics and water use efficiency under effects of four
      irrigation modes. Compared with continuous flooding irrigation, intermittent
      irrigation increased the leaf area index, photosynthetic rate and water use
      efficiency, and decreased the leaf transpiration rate. Semi-dry cultivation
      increased the leaf water use efficiency, while dry cultivation decreased the leaf
      area index, photosynthetic rate, and water use efficiency, and induced the leaf
      senescence in later growth period. Under intermittent irrigation, semi-dry
      cultivation and dry cultivation, the water consumption of paddy rice was 8. 75% ,
      17. 96% and 29. 69% lower, and its grain yield was 24. 02% higher but 5. 07% and
      38. 93% lower than that under continuous flooding irrigation, respectively. The
      water use efficiency was the highest under intermittent irrigation, relatively
      high under semi-dry cultivation, but relatively low under continuous flooding
      irrigation and dry cultivation. Compared with other irrigation modes,
      intermittent irrigation increased the milled rice rate, head rice rate and grain
      length, while decreased the chalky rice and chalkiness. With the reduction of
      water consumption, the amylose content of rice grain decreased, but the gel
      consistency and protein content increased. Intermittent irrigation could be a
      favorable irrigation mode for the paddy rice planting in Southern China.

PMID- 17209384
TI  - [Enzyme activities in nitrogen metabolism of winter wheat and its grain quality
      under different environmental conditions].
AB  - The study with three wheat cultivars grown in two places of Shandong Province
      showed that the nitrate reductase (NR) and glutamine synthetase (GS) activities
      in flag leaf and the GS activity in grain were in the sequence of Jimai 20 >
      Youmai 3 > PH971942, and higher in Longkou than in Taian. The strong gluten wheat
      cultivars in Longkou had better grain qualities than those in Taian. There were
      significant correlations between the environmental factors at grain-filling stage
      and the grain qualities and enzyme activities of wheat. Higher temperature,
      moderate drought and less sunshine at grain filling stage were benefit to the
      grain qualities. The protein content of grain was positively correlated with the
      NR and GS activities in flag leaf for the medium and strong gluten wheat
      cultivars in Longkou and for the medium gluten wheat cultivars in Taian. Wheat
      cultivars for different use needed different environmental conditions, while
      suitable environmental conditions could promote the enzyme activities in nitrogen
      metabolism of wheat, and thus, improve the qualities of wheat grain.

PMID- 17209385
TI  - [Salt resistance and its mechanism of cucumber under effects of exogenous
      chemical activators].
AB  - With root injection and foliar spray, this paper studied the effects of different
      concentrations salicylic acid, brassinolide, chitosan and spermidine on the
      growth, morphogenesis, and physiological and biochemical characters of cucumber (
      Cucumis sativus L. ) seedlings under 200 mmol x L(-1) NaCl stress. The results
      showed that at proper concentrations, these four exogenous chemical activators
      could markedly decrease the salt stress index and mortality of cucumber
      seedlings, and the decrement induced by 0. 01 mg x L (-1) brassinolide was the
      largest, being 63. 0% and 75. 0% , respectively. The activities of superoxide
      dismutase (SOD) , peroxidase (POD) and catalase (CAT) increased significantly,
      resulting in a marked decrease of malondialdehyde (MDA) content and electrolyte
      leakage. The dry weight water content and morphogenesis of cucumber seedlings
      improved, and the stem diameter, leaf number, and healthy index increased
      significantly. All of these suggested that exogenous chemical activators at
      proper concentrations could induce the salt resistance of cucumber, and mitigate
      the damage degree of salt stress. The salt resistance effect of test exogenous
      chemical activators decreased in the sequence of 0.005 -0.05 mg (L-1)
      brassinolide, 150 -250 mg x L (-1) spermidine, 100 -200 mg x L(-1) chitosan, and
      50 -150 mg x L(-1) salicylic acid.

PMID- 17209386
TI  - [Photosynthetic and growth characteristics of different ecotype capsicum under
      weak light].
AB  - This paper studied the effects of weak light on the photosynthetic
      characteristics, assimilates allocation, yield formation, and seedling growth of
      different ecotype capsicum (hot pepper and sweet pepper). The results showed that
      under weak light, the net photosynthetic rate (Pn) , dark respiration rate (Rd )
      , night respiration rate (Rn) , transpiration rate (Tr) , water use efficiency
      (WUE) , light compensation point (LCP) , CO2 compensation point (CCP) and
      carboxylation efficiency ( CE) of test capsicums decreased, while their apparent
      quantum yield (AQY) increased. The decrease of Pn was considered as a result of
      non-stomata restriction. Weak light increased plant height/stem diameter ratio
      and specific leaf area, but decreased root/shoot ratio, total dry mass, and
      seedling' s healthy index. Under the effect of weak light, the formation of
      biological and economic yields was inhibited significantly, and the allocation of
      assimilates to stem and leaf was increased while that to fruit decreased. Hot
      pepper under weak light had lower light compensation point, higher relative
      healthy index, higher relative yield per plant, and higher relative setting rate,
      showing a stronger capability of weak light tolerance than sweet pepper.

PMID- 17209387
TI  - [Effects of salt stress on the root growth and leaf water use efficiency of
      cucumber seedlings].
AB  - By the method of water culture, and with the seedlings of two cucumber cultivars
      having different tolerance to salt stress as test materials, this paper studied
      their root growth, vitality, and membrane permeability, as well as their leaf
      growth, transpiration rate (Tr) , relative water content (RWC) , and water use
      efficiency (WUE) under effects of different NaCl levels. The results showed that
      under salt stress, the absorption surface area of root was declined, whereas its
      membrane permeability was increased significantly. The leaf number per cucumber
      seedling was decreased, compared with that of the control. Both Tr and RWC were
      markedly decreased after 2 days exposure to salt stress. During the period of
      salt treatment, root vitality and leaf WUE were increased initially, but
      decreased then. For the salt-susceptible cultivar Jinchun No. 2, the decrement of
      its root vitality was 18.01% , 12. 17% and 10. 95 % higher than that of the salt
      tolerant cultivar Changchun Mici on the 9th day exposure to 50, 75 and 100 mmol x
      L(-1) NaCl, and the decrement of its leaf WUE was 2. 74% , 5. 27% and 0. 23 %
      higher than that of Changchun Mici on the 8th day exposure to 50, 75 and 100 mmol
      x L(-1) NaCl, respectively. Under short-term salt stress, the absorption capacity
      of root was raised to compensate its reduced absorption surface area, while the
      decrease of Tr and the increase of WUE could reduce the leaf water loss, which
      alleviated the imbalance between water demand and need and improved the salt
      tolerance of cucumber seedlings. After 5 days exposure to salt stress, both root
      vitality and leaf WUE decreased, which showed more severe water imbalance. It
      could be concluded that the decrease of root absorption capacity was one of the
      main reasons of water imbalance, and the decrease of leaf WUE was one of the
      responses to water imbalance. Both the absorption capacity of root and the WUE of
      leaf were closely related to the salt-tolerance of cucumber cultivar.

PMID- 17209388
TI  - [Cold tolerance and wintering cultivation effect of different Welsh onion
      varieties].
AB  - With Welsh onion Zhangqiu as the contrast, this paper measured the physiological
      indices including electrolyte leakage, malondialdehyde content, protective enzyme
      activity, chlorophyll content, photosynthetic rate and root vitality of two
      introduced Welsh onion varieties Chunwei and Changhao, and identified their cold
      tolerance and wintering cultivation effect. The results showed that during
      wintering cultivation, all test Welsh onion varieties suffered low temperature
      stress, which led the electrolyte leakage and malondialdehyde content arrived at
      the maximum, while the chlorophyll content and photosynthetic rate dropped to the
      bottom at 15 January. At this time, the function data of physiological indices
      were 0. 452, 0. 364, and 0. 226 for Chuowei, Changbao and Zhangqiu, respectively,
      suggesting that Chunwei had stronger cold tolerance, followed by Changbao, and
      Zhangqiu. The bolting rate of Chunwei, Changbao and Zhangqiu when harvested was
      0, 35.2% and 81.0% , respectively. Although the biological yield of Changbao was
      25.67% and 52. 94% higher than that of Chunwei and Zhangqiu, respectively, the
      economic yield of Chunwei was the highest (5.49 kg m2) , with an increment of 18.
      57% than Changbao, and that of Zhangqiu was only 0. 86 kg x m(-2) It could be
      concluded that Chonwei was fit to cultivate in low tunnel in winter, while
      Zhangqiu was weaker in cold tolerance and not fit to wintering cultivation.

PMID- 17209389
TI  - [Dry matter accumulation and allocation models of rice in FACE].
AB  - A fertilization experiment with 150 kg N x hm(-2), 250 kg N xhm(-2) and 350 kg N
      x hm(-2) was conducted on the free-air CO2 enrichment (FACE) platform at Wuxi of
      Jiangsu Province in 2001-2003, aimed to build a simulation model of dry matter
      accumulation and allocation of rice in FACE. Physiological development time and
      CO2 concentration were selected as the driving factor and the main affecting
      factor, respectively, and nitrogen application rate was introduced as the factor
      adjusting the dry matter accumulation and allocation in green leaf, stem and
      panicle. The results showed that with the increase of atmospheric CO2
      concentration, the dry matter accumulation in above-ground part of rice increased
      remarkably, but the allocation index dropped in green leaf, changed little in
      panicle, while increased in stem at early stage and equaled to the CK at last.
      The model was tested with different experimental data, and the results indicated
      that the model had high fitting degree and preferable applicability and
      predictability.

PMID- 17209390
TI  - [Energy accumulation and caloric value in yield-forming process of different rice
      cultivars].
AB  - Based on the determination of dry matter and caloric value, this paper studied
      the characteristics of energy accumulation and the dynamics of caloric value in
      the yield-forming process of rice cultivars Shanyou 63 ( three-line hybrid rice)
      , Liangyou 2186 (two-line hybrid rice) , and IR64 (conventional rice). The
      results showed that at fully grain-maturing stage, the amount of dry matter in
      Shanyou 63, Liangyou 2186 and IR64 was 1926. 38 g x m(2), 1933.80 g x m(-2) and
      1842.30 g x m(-2), and that of accumulated energy was 31,137.05 kJ x m(-2) 31
      060.63 kJ x m(-2) and 30 454.89 kJ x m(-2) , respectively, showing no significant
      difference among the cultivars. In the process of grain filling, the apparent
      transformation ratio of energy in Shanyou 63, Liangyou 2186 and IR64 was about
      38. 95% , 28. 38% and 32. 66% , respectively, implying that the energy flow in
      Shanyou 63 and IR 64 was smoother than that in Liangyou 2186, and the output of
      energy from stem to the sink of grain was blocked in Liangyou 2186. The ratio of
      energy partitioning to the sink of grain was 53. 03% , 46. 43% and 50. 11% for
      Shanyou 63, Liangyou 2186 and IR64, respectively, showing the energy partitioning
      heterosis in three-line hybrid rice Shanyou 63. As for the caloric value, it had
      no significant difference among the three cultivars, but decreased in the order
      of leaf> grain > sheath > stem > root, ranging from 16.81-17.25 kJ x g(-1) ,
      15.89-16.54 kJ x g (-1) 14.33-15.49 kJ x g(-1) , 14.23-15.15 kJ x g , and 11.51
      13.25 kJ x g(-1), respectively. It was also shown that there was a significant
      positive correlation of caloric value with carbon content, chlorophyll a content,
      and nitrogen content in rice plant, with the determination coefficient R(2) being
      0.609, 0.471 and 0.485, respectively.

PMID- 17209391
TI  - [Dynamic prediction and evaluation method of maize chilling damage].
AB  - In order to prevent and alleviate the chilling damage of maize, a dynamic
      prediction and evaluation method on its emergence and loss was developed by using
      an improved dynamic model of maize growth and dry matter accumulation, and new
      parameters and damage indices. The method followed the thermal constant theory
      and the principles of maize biology and ecology, utilized relative accumulated
      temperature as the leading factor of maize development stage prediction and
      damage discretion, and took dry matter shortage rate as the loss rate of the
      damage. The results of test and tryout showed that the method was objective and
      applicable, and suited for various places of Northeastern China through areal
      adjustment of parameters and indices.

PMID- 17209392
TI  - [Estimation of N loss loading by runoff from paddy field during submersed period
      in Hangjiahu area].
AB  - As the largest bread basket in Zhejiang Province, Hangjiahu area is facing more
      and more serious water pollution, while the N loss loading by runoff from the
      paddy field during its submersed period is the main cause of the pollution.
      Through field experiment and fixed spot observation, the model of precipitation -
      runoff in Yangtze delta was testified, and the results showed that the
      precipitation - runoff model from HE Baogen was basically accorded with the fact
      after considering the impact of field overflow mouth, and the error was between -
      19. 9% and + 18. 0%. The model of N concentration with precipitation - runoff in
      paddy field during submersed period was brought forward, with the R value being
      0. 948. These two models consisted of the model of N loss loading by runoff from
      paddy field during submersed period. Based on this model as well as the past 30
      years data of fertilization and precipitation, 1: 250,000 topography map, land
      use map, and water system map, the N loss loading and its distribution were
      estimated by using GIS method, and the results showed that the N loss loading was
      different from place to place, with an average of 35.26 kg N x hm(-2), and
      accounting for 12. 69% of the applied N. The N loss loading in Anji and Yuhang
      with obviously more precipitation was higher than that in other places, while
      Haining also had a serious N loss problem because of the huge amount of applied
      N.

PMID- 17209393
TI  - [Urban greenbelt eco-service value of Hangzhou City under effects of land use
      change: an evaluation with CITYgreen model].
AB  - Based on the Landset TM information of land use/cover change and greenbelt
      distribution in Hangzhou city in 1994 and 2004, and by using CITYgreen model,
      this paper estimated the eco-service value of urban greenbelt in the city under
      the effects of land use change and economic development. The results showed that
      in the 10 years from 1994 to 2004, the greenbelt area in the city decreased by
      20. 4% , while its eco-service value increased by 168 million yuan. The annual
      increment of greenbelt eco-service value and GDP was 111.92% and 5. 32% ,
      respectively. Suitable adjustment of land use pattern in the city harmonized the
      relationships between urban economic development and urban eco-function, and
      achieved higher eco-service efficiency of land utilization.

PMID- 17209394
TI  - [Application of entropy weight and fuzzy synthetic evaluation in urban ecological
      security assessment].
AB  - Ecological security is one of the foundations of regional security, and the basis
      of sustainable development. Urban ecological security refers to the ecological
      support and main ecological issues of a city, which do not threaten its survival
      and development. To develop the research method on the ecological security of
      urban social-economic-natural complex ecosystem, an assessment indicator system
      of urban ecological security was set up based on Pressure - State - Response
      Model, which included 3 key factors and 33 concrete items. The five most
      developed cities of China were taken as the cases to assess their ecological
      security situation by using entropy weight and fuzzy synthetic evaluation method.
      The results showed that the urban ecological security of Suzhou and Beijing was
      at relatively safe level, while that of Shenzhen, Shanghai and Guangzhou was
      critical safe in the year of 2003. The urban ecosystem of Shenzhen was under
      heavy press, while that of Suzhou behaved best both in system status and system
      response. Comparing with other assessment methods, this evaluation method was
      easier and more reasonable. The results were basically consistent to the fact of
      these cities, suggesting that the urban ecological security indicator system and
      the entropy weight and fuzzy synthetic evaluation approach were feasible to some
      extent.

PMID- 17209395
TI  - [Predation of Axinoscymnus cardilobus to Bemisia tabaci].
AB  - The laboratory study on the predation of Axinoscymnus cardilobus to Bemisia
      tabaci showed that the functional response of A. cardilobus to B. tabaci was of
      Holling' s type II. With the increasing age of B. tabaci, the searching rate of
      A. cardilobus adult decreased, and its handling time became longer. The searching
      rate of A. cardilobus larva was increased with its age, and the handling time
      became shorter. The mutual interference in individual predator could be described
      by Hassell and Varley equation, and the relationship between predation ratio (E)
      and natural enemies density (P) was E =0. 5205P(-0 6631.) The predation
      efficiency (E) of predator varied with environmental temperature, and the effects
      of the temperature on search rate (a) and handling time ( T ) could be described
      by a = -0. 0002T(3)+ 0. 0166T(2) - 0. 3492T + 3. 2329 and Th = 4 x 10 (-7) T-( 3)
      x 10(-5) T(2) + 0.0006T 0.0009, respectively.

PMID- 17209396
TI  - [Control effect of natural enemies on Plutella xylostella under ecological
      restoration condition].
AB  - A field study on the life table of diamondback moth (DBM) Plutella xylostella
      showed that the population increase index of DBM in chemical control plot was
      52.52, while that of four continuous generations of DBM in ecological restoration
      plot was 16. 9, 7.16, 3.71 and 4.02, respectively, indicating that the control
      effect of natural enemies on target pest was greatly improved. The main factor
      affecting the first and forth generations of DBM was the parasitism of Cotesia
      plutella, while those affecting the second and third generations of DBM were the
      predator of the 4'h instar larva and the parasitism of Trichogramma, with the
      corresponding exclusive index of population control (EIPC) being 1.39, 1.54, 1.56
      and 1.74, respectively. There was an obvious time lag effect of natural enemies
      on their target pest, and thus, to protect and multiply the population of natural
      enemies in the field should be the key point of fully exerting the potential of
      natural enemies in their pest control.

PMID- 17209397
TI  - [Effects of cropping system and cultivation pattern on bacterial populations and
      anti-fusarium wilt bacteria in melon soils].
AB  - A total of 132 soil samples were collected from Xinjiang, Fujian and Zhejiang
      provinces to study the effects of different cropping system and cultivation
      pattern on the amount of bacterial populations and the distribution of anti
      fusarium wilt bacteria in melon soils. The results of plate counting showed that
      the amount of culturable bacteria was 15.2 times higher in melon soils than in
      uncultivated soil, 1.0 times higher in rhizosphere than in non-rhizosphere, 2.5
      times higher in the soil with rotation than in that with monoculture, and 0.5
      times higher in the soil with non-graft than in that with graft. The Biolog
      determination of anti-fusarium wilt bacteria in melon soils showed that the soil
      with water-drought rotation or graft had more antagonistic bacteria, and more
      than 80% of them were classified as fluorescent Pseudomonas spp.

PMID- 17209398
TI  - [Sustainable rice pest management and its economic benefits].
AB  - With rice varieties Jiahua 1 (resistant to the white backed plant hopper
      Sogatella furcifera) and Shanyou 63 (susceptible) as test materials, this paper
      studied the effects of different insecticide treatments on the pest population
      and quality and yield of rice grain, and evaluated their actual economic benefits
      (AEB). The results indicated that in the control plot, the peak density of S.
      furcifera on Jiahua 1 was only 1/10 of that on Shanyou 63. Throughout the whole
      rice growth period, the S. furcifera population on Jiahua 1 kept below economic
      injury level, while Shanyou 63 suffered heavy infestation by S. furcifera. The
      spider density in the control plot was 3 -7 times higher than that in the plots
      treated with insecticide following farmers' practice. No application of
      insecticide decreased the grain yield of Jiahua 1 and Shanyou 63 by 11. 8% and
      43.4% , respectively. Compared with the control, spraying with insecticide one
      time decreased the AEB of Jiahua 1 and Shanyou 63 by 0.9% - 2.6% and 2.6% - 4.7%
      , respectively. Without insecticide application, the AEB of Shanyou 63 decreased
      by 32.9% - 36.1% , while that of Jiahua 1 increased by 2.2% - 4.8%. The income of
      planting Jiahua 1 without insecticide application was 9403 yuan x hm(-2) , which
      was remarkably higher than that (8632 yuan hm (-2)) of Shanyou 63 protected by
      spraying insecticide 3 times. It was worthwhile to point out that insecticide
      treatment did not affect the processing of rice grain and its commercial and
      edible quality, but decreased its protein content of Jiahua 1 and Shanyou 63.

PMID- 17209399
TI  - [Enrichment and toxicity effect of heavy metals in soil ecosystem].
AB  - The study on the heavy metals-polluted soil of Qingshuitang District, Zhuzhou
      City showed that the main enriched heavy metals in the soil were Cd, Hg, As, Zn,
      Pb and Cu, among which, the former three had strong biotoxicity while the others
      had definite toxicity, with the average integrative pollution index being 6.40.
      The heavy metals enrichment in soil animals increased with increasing pollution
      degree. Especially for some species of Megascoiecidae, they had a high enrichment
      of Cd, with the enrichment index being 11.96. The species and quantity of soil
      animals decreased with increasing Cd concentration. Cd had an obvious biotoxic
      effect on Megsacoiecidae' s isozyme activity. The heavy metals enrichment in
      vegetables also increased with increasing pollution degree, but there existed
      obvious interspecies difference in Cd enrichment.

PMID- 17209400
TI  - [Effects of chlorine ion and EDTA on cadmium availability to plants].
AB  - In a water culture experiment with rice and rape, different concentrations of
      chloride or EDTA were added to study the effects of chlorine ion and EDTA
      complexation on the uptake of cadmium by the plants. The results showed that the
      cadmium concentration in the shoots and roots of test plants decreased with
      increasing concentration of chloride or EDTA. With the increase of Cl-
      concentration, the cadmium content in rice shoot and root decreased from 212.2 mg
      x kg (-1) and 345. 1 mg x kg - to 34.1 mg x kg(-1) and 209.1 mg x kg(-1) ,
      respectively. EDTA addition decreased the cadmium content in rice shoot and root
      from 212.2 mg x kg (-1) and 345.2 mg x kg(-1) to 50.0 mg x kg(-1) and 4.2 mg x
      kg(-1) , and that in rape shoot and root from 86.7 mg x kg(-1) and 149. 2 mg x
      kg(-1) to 22.2 mg x kg (-1) and 12. 3 mg x kg(-1 ), respectively. EDTA also
      affected the cadmium translocation from root to shoot. The complexation of Cl- or
      EDTA with cadmium reduced the uptake of Cd by plants, and the effect of EDTA was
      more obvious than that of Cl -.

PMID- 17209401
TI  - [Effects of methamidophos and copper on ecological detoxification of acetochlor
      by earthworm in phaeozem].
AB  - By using microcosm culture method, this paper studied the dynamic changes of
      acetochlor degradation by earthworm in phaeozem with methamidophos or copper
      addition, aimed to approach the feasibility of using earthworm to intensify the
      detoxification of acetochlor. The results showed that the dynamics of acetochlor
      degradation accorded with the first-order reaction kinetics, whether earthworm
      existed or not. The activities of earthworm accelerated the detoxification of
      acetochlor, and the coexistence of methamidophos or copper with acetochlor
      evidently inhibited the degradation of acetochlor. The coexistence of
      methamidophos and acetochlor or of copper and higher concentration acetochlor
      altered the dynamics of acetochlor degradation, while the coexistence of copper
      and lower concentration acetochlor didn't have any obvious effect on the
      detoxification of acetochlor.

PMID- 17209402
TI  - [Contribution of seed size and its fate to vegetation renewal: a review].
AB  - Seed is the reproductive body of spermatophytes, and its resource devotion has a
      direct effect on the offspring fitness and the renewal of vegetation community.
      Generally, larger size seed has the superiorities of higher germination rate and
      seedling' s establishment, while smaller size seed has the advantages in escaping
      the predation of animals and birds, forming soil seed bank, and exhibiting larger
      potentiality of vegetation renewal. Under various kinds of stress, different size
      seed has different fate in its life history, and has different contribution in
      vegetation renewal. This paper reviewed the research findings on the contribution
      of seed size and its fate to vegetation renewal, and presented some suggestions
      regarding the domestic research in the future.

PMID- 17209403
TI  - [Application of chlorophyll fluorescence analysis in forest tree cultivation].
AB  - In recent years, chlorophyll fluorescence analysis has been developed into a kind
      of new, fast, simple, and accurate technique in photosynthesis research, and
      widely applied in agriculture and horticulture but few in forest tree
      cultivation. This paper introduced the relevant parameters of chlorophyll
      fluorescence analysis and their biological meanings, and summarized its
      application in forest tree cultivation and in the research of forest tree stress
      physiology. Some perspectives and suggestions were put forward.

PMID- 17209404
TI  - [Degradation of main ecosystems in South China Sea and corresponding conservation
      countermeasures].
AB  - South China Sea is a significant area of global biological diversity. Due to the
      long-term unreasonable exploitation and utilization, the habitat there
      degenerates obviously, and the biodiversity loses seriously. The estimated annual
      loss of mangrove area ranges from 0.5% to 3.5% , and that of seaweed area is from
      20% to 50%. A total of 82% of coral reefs in the Sea display evident degradation.
      In this paper, a trans-boundary diagnostic analysis of ecosystem degradation in
      South China Sea was conducted, with the focus on mangrove, seaweed and coral
      reef. Based on the analysis of the destruction state of the existing ecosystems
      as well as the main causes of habitat degradation and its trans-boundary impacts,
      some countermeasures on habitat conservation and management were put forward,
      aimed to promote the cooperation both at national and at regional levels to
      implement appropriate approach to reverse the ecosystem degradation trend in
      South China Sea.

PMID- 17209405
TI  - [Research progress on ecological footprint analysis].
AB  - Ecological footprint (EF) model, as an indicator of sustainability, has received
      broad attention and wide use. With the development and refinement of the research
      work on EF theory and methodology, it appeared various methods which can be
      applied at different scales. Ecological footprint analysis has been combined with
      material flow analysis, life cycle assessment or input-output analysis, and
      especially, the newest progress in EF methods called allocating EF to final
      consumption categories with input-output analysis helps to develop a
      "standardized" EF. In this paper, the underlying causes of these methods were
      interpreted theoretically, and the research methods were classified into progress
      analysis and input-output analysis (IOA). In addition, the compound and component
      based methods as well as IOA were introduced, with their respective features,
      application, and development progress discussed. A prospect on the development of
      EF in term of the tendency and application of EF methods in China and abroad was
      given, i. e. , the common framework should be built at the national and regional
      scales by using compound analysis, IOA and component-based analysis are expected
      to develop their application

PMID- 17209406
TI  - [Major chemical components of poultry and livestock manures under intensive
      breeding].
AB  - Owing to the wide use of feed additives in modern intensive poultry and livestock
      production, the major components and their concentrations of domestic animal
      manures may be greatly changed, as compared with those in traditional breeding.
      An investigation on the 61 samples of chicken, pig and pigeon manures from the
      intensive poultry and livestock farms of Guangdong Province showed that the
      concentrations of total N, P and K in chicken and pig manures were obviously
      higher than those of traditional breeding, and the P/N ratio of three test
      manures was greater than that of common crops. The concentrations of total
      soluble salts (TSS) of test manures averaged 49.0, 20.6 and 60.3 g x kg(-1) ,
      respectively, which were mainly composed of the sulfate and chloride of potassium
      and sodium. The mean concentrations of Cu, Zn and As reached 107.5, 366.6 and
      21.6 mg x kg (-1) in chicken manure, 765.1, 1128.0 and 89.3 mg x kg(-1) in pig
      manure, and 56.1, 210.9 and 2.9 mg x kg(-1) in pigeon manure, respectively. These
      manures were low in Pb, Cd and Cr contents, from non-detectable to 12.0 mg x kg(
      1). According to the limiting criteria of heavy metals in fertilizers, the Cu, Zn
      and As in the three manures were the major elements exceeding the limits,
      especially for Zn.

PMID- 17209407
TI  - [Separation of protein and isoflavone in soybean whey by ultrafiltration].
AB  - The study on the technical conditions of separating protein and isoflavone in
      soybean whey by ultrafiltration showed that before ultrafiltration, soybean whey
      should be pretreated to reduce membrane contamination. The orthogonal experiment
      of 2 factors and 3 levels indicated that the optimum pretreatment conditions were
      5% of CaCl, addition based on the solid substance content in soybean whey, and
      heating up at 85 degrees C for 15 minutes. Under these conditions, the
      precipitation rate of whey protein was 49. 8% , while the reservation rate of
      isoflavone was 90.4%. Single factor experiment showed that the optimum
      ultrafiltration conditions were poly (ether sulfone) membrane of 10 kDa molecular
      weight cut-off (MWCO), 51-68 kPa, and 30 degrees C-40 degrees C. Under these
      conditions, the retention rate of whey protein and isoflavone was 83.9% and 7.6%
      , respectively.

PMID- 17209408
TI  - [Halophilous microbial groups in saline lake of Qinghai and the growth
      characteristics and anti-microbial and anti-tumor activities of F16].
AB  - A total of forty-five halophilous microorganisms were isolated from the sediment
      of saline lake in Qinghai Province, among which, filamentous fungus F16 showed
      the highest activity of anti-microorganism and anti-tumor. The ethyl acetate
      extract of F16 culture filtrate showed a strong cytotoxicity, and could inhibit
      the growth of four kinds of bacteria, especially Escherichia coli. When the
      concentration of the crude extract was 50 microg x ml(-1), the inhibition rate to
      liver cancer cell BEL7402 reached 76. 91%. The optimal temperature for F16 growth
      was 15 degrees C , and the increase of salt concentration in media would inhibit
      its growth. When the concentration of salt surpassed 15% , F16 could not survive.
      F16 grew well when the pH value ranged from 5 to 9.

PMID- 17209409
TI  - Is amnio right for you?

PMID- 17209410
TI  - Modern neuropsychology in France: Henry Hecaen (1912-1983) and the Sainte-Anne
      Hospital.

PMID- 17209411
TI  - Impact factor: does the 80/20 rule apply to Cortex?

PMID- 17209412
TI  - The future for SNARC could be stark...
AB  - The present report by Wood et al. (2006, this issue) invites us to reconsider
      what we should believe about the cognitive representation of numbers. Researchers
      interested in numerical cognition have quickly embraced the idea that systematic
      spatial performance biases in number-related tasks must reflect an inherent
      spatial attribute of the underlying cognitive representation of numbers. The
      association between numbers and space (SNARC--spatial numerical association of
      response codes--effect) has effectively been used to augment the "mental number
      line" metaphor. Here I discuss the possibility that the SNARC effect is merely an
      instance of strategic problem solving.

PMID- 17209413
TI  - Crossed hands and the SNARC effect: a failure to replicate Dehaene, Bossini and
      Giraux (1993).
AB  - Dehaene et al. (1993, Experiment 6) presented evidence that the mental number
      line is left-to-right oriented with respect to representational associations and
      not with respect to left and right hands. Here we tried to replicate the study of
      Dehaene et al. (1993) in a larger sample (n = 32) using four different stimulus
      notations (Arabic numbers, number words, auditory number words, and dice
      patterns). As in the study by Dehaene et al. (1993), the spatial numerical
      association of response codes (SNARC) effect was examined with an incongruent
      hand assignment to left/right response keys (crossed hands). In contrast to
      Dehaene et al. (1993), we did not observe a SNARC effect in any condition. Power
      analyses revealed that n = 32 should have been large enough to detect SNARC
      effects of usual size. Furthermore, time-course analyses revealed no SNARC slope
      in faster and slower responses, so that the null effect could not be due to
      relatively slow responses with crossed hands. Joint analyses with previous data
      (Nuerk et al., 2005b) revealed significantly steeper SNARC slopes with congruent
      hand assignment, and no interaction between hand assignment and notation.
      Altogether, these findings suggest that the results of Dehaene et al. (1993) only
      hold under specific conditions. Differences between studies are discussed. We
      suggest that spatial context has an influence on the SNARC effect and that hand
      based associations (and not only representational associations) are relevant for
      the SNARC effect.

PMID- 17209414
TI  - Episodic memory in patients with focal frontal lobe lesions.
AB  - Episodic memory was evaluated in patients with unilateral, frontal lobe damage
      and matched controls using a list-method directed forgetting paradigm. Directed
      forgetting instructions (forget vs. remember the word), encoding instructions
      (learn vs. judge the word) and test format (recall vs. recognition) were
      manipulated in order to explore how variations in encoding and retrieval affect
      verbal memory. Controls demonstrated a normal directed forgetting effect in
      recall and less directed forgetting in recognition. Patients with left frontal
      (LF) damage did not show directed forgetting in either recall or recognition and
      patients with right frontal (RF) damage showed directed forgetting in recall, but
      not in recognition. Furthermore, the LF group recalled significantly more of the
      judge than learn words, suggesting that this group's performance improves by
      providing them with an encoding strategy. Conversely, the RF group's performance
      did not depend on encoding instructions and their recognition memory was impaired
      relative to the other two groups when they were instructed to judge the words.
      Our results suggest that (a) patients with LF damage show deficits in the
      rehearsal of to-be-remembered information, (b) whereas patients with RF damage
      show impairments in recognition memory. Furthermore, both patient groups show a
      lack of directed forgetting when familiarity-based processes guide performance.

PMID- 17209415
TI  - Functional anatomy of derivational morphology.
AB  - Lexical morphology involves two types of suffixes: inflectional suffixes, which
      have a grammatical function, and derivational suffixes with a word formation
      function. In this study, functional magnetic resonance imaging (fMRI) was used
      during processing of Italian derived and inflected words. In the derivational
      task, subjects were asked to produce nouns derived from verbs and from adjectives
      (e.g., to observe--observation; kind--kindness). After the presentation of the
      derived noun, they had to generate the corresponding verb (e.g., failure--to
      fail: generation task). In the inflectional task, subjects had to produce the
      past participle of the verb or the plural form of the adjective or the derived
      noun. Behavioural data were collected in separate sessions in two different
      conditions. In the first experiment, as in the fMRI study, vocal reaction times
      (RTs) were measured from the offset of the auditory stimulus to the onset of the
      participant's response. In the second experiment, run with a different group of
      participants, RTs were recorded starting from the onset of the auditory stimulus
      to the onset of the response. The fMRI results showed that, relative to the
      inflectional task and to a repetition task, the derivational task, but not the
      verb generation task, brought about an activation of left fronto-parietal
      regions, documenting a specific involvement of these areas in the processing of
      derived words. Although less extended, similar activation was found for verb
      inflection but was absent for noun and adjective plural forms. Analysis of
      behavioral data indicated that an explanation in terms of task difficulty was
      unlikely related to the imaging results.

PMID- 17209416
TI  - Brain morphology and neuropsychological profiles in a family displaying dyslexia
      and superior nonverbal intelligence.
AB  - Behavioral research suggests that individuals with dyslexia may have exceptional
      skills in nonverbal cognitive processes, while genetic studies have noted that
      giftedness, high IQ and/or special talents tend to run in families. Taken
      together, these results suggest that persons within families (particularly
      offspring) may share similar cortical systems supporting those functions.
      Postmortem and in vivo imaging studies have linked dyslexia to abnormalities in
      the structures associated with the parietal operculum (PO) (e.g., planum
      temporale, supramarginal gyrus, and angular gyrus). In this paper we present data
      on a single family showing a link between dyslexia, superior nonverbal IQ and
      atypical PO presentation. We consider the psychometric and neurological patterns
      of this family as a tentative etiological test of the putative dyslexia-talent
      association.

PMID- 17209417
TI  - Breaking ranks: space and number may march to the beat of a different drum.
AB  - Number processing can evoke spatial representations and cause lateralized
      attention shifts. The article by Wood et al. suggests interesting considerations
      about the mental space of numbers by pointing to a difference between physical
      and numerical space processing. We read Wood et al.'s findings in a perspective
      that takes into consideration a currently debated issue, that is the relation
      between Simon and SNARC effects. By pointing to a difference between peripheral
      onsets and numerical targets, indeed, their finding suggests that the hypothesis
      of a complete overlap between Simon and SNARC effects is less plausible than a
      partial overlap hypothesis.

PMID- 17209418
TI  - Effects of interhemispheric communication on two-digit arabic number processing.
AB  - We investigated interhemispheric communication and hemispheric style differences
      (analytic vs. holistic) in two-digit Arabic number comparison by employing the
      divided visual field paradigm. Interhemispheric communication modulated two-digit
      number comparison in a very specific way. While no advantage of interhemispheric
      communication was found with unit-decade compatible trials (e.g., 52 and 67, the
      decade comparison and unit comparison of the two numbers lead to the same
      response; see Nuerk et al., 2001), a significant advantage of interhemispheric
      interactions emerged in the attentionally more demanding incompatible trials
      (e.g., 47 and 62, decade and unit comparisons do not lead to the same response,
      because 4 < 6 but 7 > 2), thereby enhancing the efficiency of selective attention
      (c.f., Banich, 1998). Additionally, some results indicated a more analytical
      processing style in the left hemisphere and a relatively more holistic processing
      style in the right hemisphere.

PMID- 17209419
TI  - Visual spatial neglect in multiple sclerosis.
AB  - Neuropsychological dysfunction in multiple sclerosis (MS) patients is now a well
      established clinical finding. We examined the entity of visual spatial neglect in
      demyelinating disease and its correlation to the functional and neuroradiological
      parameters. The phenomenon of visual spatial neglect was examined in 20 (5 male
      and 15 female) MS patients. Two different examination methods were used--the line
      bisection test and the random shape cancellation test. The results were compared
      with 20 aged matched control individuals. The correlation of the visual spatial
      neglects to neurological deficits and handicaps, using Kurtzke's Expanded
      Disability Status Scale (EDSS), as well as with the MRI's neuroradiological
      findings, was analyzed. A highly significant different result on the line
      bisection test for three various line lengths (p = .006, p < .0001, p < .001)
      with displacement towards the right side was found. In all the cancellation
      subtests, a significant difference in error rate was found in comparing patients
      to controls toward a higher one on the left side of the MS patients (p = .005, p
      < .002, p < .0001 and p = .02 in the left side subtest, and p = n.s. in the right
      side subtest). There was no significant correlation between the cancellation
      tests and bisection results and the EDSS scale data, as well as with the
      neuroradiological findings. The present results demonstrate the presence of
      visual spatial neglect among MS patients, even without the demonstration of a
      characteristic neuroanatomical lesion. The hypotheses for this finding are
      discussed with a stress on the possibility of disruption of multiple
      intrahemispheric connections, especially under the condition of asymmetry of
      dominance regarding spatial attention.

PMID- 17209420
TI  - [Identification of beta-aggregate sites in protein chain].
AB  - Studying amyloid diseases (amyloidoses) has been especially actual and has
      attracted the attention of researchers all over the world in connection with the
      appearance of epidemic prion diseases such as Bovine Spongiform Encephalopathie
      in cattle and Creutzfeldt-Jakob in human. Amyloidoses are caused by transition of
      a "healthy" protein molecule or peptide from a native conformation to a very
      stable pathologic form: molecules in a pathologic conformation aggregate, that
      results in the amyloid fibrils which can grow infinitely. Investigation of
      molecular mechanisms of these diseases and the ability to find protein regions
      responsible for the appearance of the given diseases is a fundamental problem.
      Theoretical and experimental studies of amyloid fibril formation are considered
      in this review.

PMID- 17209421
TI  - [Stress granules: RNP-containing cytoplasmic bodies springing up under stress.
      The structure and mechanism of organization].
AB  - In this review recent data describing stress granules are summarized. Stress
      granules are specific RNA-containing structures in the cytoplasm of living cells
      which arise under stress conditions (e. g. heat shock, UV irradiation, energy
      depletion and oxidative stress). It became evident that stress granules
      accumulate non-canonical 48S initiation complexes and contain mRNA with
      associated proteins, small ribosomal subunits and some initiation factors. Stress
      granules are depleted with ternary complex and large ribosomal subunit. It's
      proposed that eIF2alpha phosphorylation and ternary complex decrease can be a
      trigger for stress granule formation. Shuttling nuclear and cytoplasmic RNA
      binding protein TIA-1 plays a crucial role in this process. It's proposed that
      TIA-1 forms prion-like aggregates, and these aggregates are scaffolds for other
      components of stress granules. Cytoskeletal structures facilitate the
      accumulation of stress granule components in local cytoplasmic sites.
      Investigation of process of stress granule formation is important for
      understanding of cell reaction to stress and translation regulation mechanisms.

PMID- 17209422
TI  - [Role of transcription factor AP-1 in integration of cellular signalling
      systems].
AB  - Transcription factor AP-1 is a dimer complex composed by DNA-binding proteins of
      Jun, Fos, and ATF families. AP-1 mediates cell response on growth factors,
      cytokines, neurotransmitters and other intercellular signaling molecules. AP-1
      activity is mediated by G-proteins, adapter proteins, MAP kinases and other
      elements of cellular signaling systems. AP-1 dependent genes play a pivotal role
      in regulation of cell proliferation, morphogenesis, apoptosis, and
      differentiation.

PMID- 17209423
TI  - [Inhibitors of ribonucleases].
AB  - RNases are the most important enzymes of cellular metabolism. They influence gene
      expression, cell growth and differentiation, participate in cell protection
      against pathogens and induction of apoptosis. Since intracellular RNases exist
      mainly in complexes with their inhibitors, the latter are also involved in all
      above-mentioned processes. The review describes natural protein inhibitors of
      animal, plant, and bacterial RNases along with synthetic low molecular-weight
      inhibitors. Special attention is paid to the perspectives of application of RNase
      inhibitors to therapy of oncological and allergic diseases. Despite wide
      distribution of RNases and their numerous studies, the number of available
      natural and synthetic inhibitors of these enzymes remains limited. Creation of
      highly efficient low-molecular inhibitors of RNase activity of angiogenin and
      eosinophil-associated RNases, aimed at the therapy of oncological and allergic
      diseases, still remains quite actual.

PMID- 17209424
TI  - [Low-molecular weight inhibitors of bacterial DNA-dependent RNA polymerase].
AB  - In this review, current data on low molecular weight inhibitors of bacterial RNA
      polymerases, both classical and those recently discovered, are summarised. This
      area has progressed rapidly in recent years largely due to availability of high
      resolution structures of RNA polymerase and its complexes with inhibitors. The
      structural information, together with biochemical data, allows to understand
      molecular mechanisms of transcription inhibition by rifampicin, sorangicin,
      tagetitoxin, streptolydigin, and microcin J25. In its turn, the mechanistic
      understanding of the action of these inhibitors provides better understanding of
      transcription mechanism and RNA polymerase structure-function.

PMID- 17209425
TI  - [Artifitial increase of HIV-1 reverse transcriptase turnover through proteasome
      pathway].
AB  - Proteasome plays a key role in antigen presentation through MHC class I pathway.
      Thus, approaches are actively developed to increase proteasome targeting of DNA
      vaccine encoded proteins. Gene of reverse transcriptase of HIV-1 is used in DNA
      vaccines. It was shown, that revertase degraded in cells slowly (half-life is 18
      20 h). Revertase content increased in presence of proteasome inhibitors MG132 and
      epoxomicin indicated that it degraded by proteasome. Level of protein was 2 fold
      higher after treatment with MG132 then after epoxomicin treatment. Since
      epoxomicin is more specific proteasome inhibitor it indicated that other cellular
      proteases can take part in revertase degradation. With the aim to increase
      affinity and degradation rate by proteasome of revertase we have to add strong
      degradation signal. Ornithine decarboxylase contains this kind of signals, it's
      unique properties are fast degradation by proteasome in ubiquitin-independent
      manner. As result fusion protein of revertase and ornithine decarboxylase was
      created. Half-life of fusion protein was 6 time less than revertase (3 h).
      Degradation of fusion protein was blocked by proteasome inhibitors 10 times
      stronger than revertase. Thus, degradation by proteasome pathway of reverse
      transcriptase was enhanced by fusion with ornithine decarboxylase. Performance of
      this fusion could improve presentation of revertase in DNA-vaccine.

PMID- 17209426
TI  - [Analysis of nucleotide sequences polymorphism of chloroplast trnL-trnF spacer of
      tRNA genes in giant duckweed Spirodela polyrrhiza (L.) Schleiden].
AB  - Chloroplast DNA trnL-trnF spacer sequences of tRNA genes of 14 specimens of the
      fam. Lemnaceae have been characterized. Nucleotide polymorphism analysis of the
      spacer trnL-trnF of geographically isolated and morphologically differing
      accessions of S. polyrrhiza that is the most widespread species of Spirodela
      genus showed the low level of intraspecific variability. Five trnL-trnF
      haplotypes of S. polyrrhiza are identified. Both mono-, and polynucleotide
      repeats, and also extensive indels, specific to representatives Spirodela
      polyrrhiza, Landoltia punctata and Lemna sp. are revealed. Competency of
      Landoltia genus allocation as separate entity was confirmed.

PMID- 17209427
TI  - [Characterization of low-molecular-weighT i-type glutenin subunit genes from
      diploid wheat in relation to the gene family structure].
AB  - The low-molecular-weight (LMW) glutenin subunits are important for aspects of
      wheat quality and dough processing, and the LMW-i type glutenin is one of the
      typical glutenins. However, a detailed description of the DNA structure and
      encoded polypeptides of the LMW-i type glutenin subunit gene family is still
      lacking. In this study, two LMW-i type glutenin subunit genes, i.e., LMW-Eb from
      Triticum boeoticum and LMW-Em from T. monococcum, were obtained from genomic DNA,
      respectively. The LMW-Eb is a novel gene and the LMW-Em has the identical
      sequence with a known gene. To comprehensively understand the LMW-i type glutenin
      subunit gene family structure, all known LMW-i type glutenin subunit genes were
      comparatively analyzed. Detailed comparison of these genes revealed a high-level
      of single nucleotide polymorphisms (SNP). In these LMW glutenin subunits, the
      percentage of glutamine and proline were approximately 38.27 and 12.77%,
      respectively. They started directly from the repetitive domain with ISQQQ- after
      the signal sequence, which the N-terminal regions were absent. In addition, there
      are three consensus repeat motifs (i.e. PPFSQQQQ, PPISQQQQ and PPYSQQQQ) in the
      repetitive domains of these LMW glutenin subunits. The C-terminal I domain is the
      most conserved region, while the domains of C-terminal II and III are more
      variable. The eight cysteine residues are highly conserved. These genes could be
      clustered into two major groups, among which one group could be further divided
      into five subgroups. Furthermore, to date, all known LMW-i type glutenin subunit
      genes are located on chromosome 1A, whereas no LMW-i type glutenin subunit gene
      is obtained from the B and D genomes in wheat.

PMID- 17209428
TI  - [Oxidase gene from sweetpotato].
AB  - Polyphenol oxidase is the enzyme responsible for enzymatic browning in
      sweetpotato that decreases the commercial value of sweetpotato products. Here we
      reported the cloning and characterization of a new cDNA encoding PPO from
      sweetpotato, designated as IbPPO (GeneBank accession number: AY822711). The full
      length cDNA of IbPPO is 1984 bp with a 1767 bp open reading frame (ORF) encoding
      a 588 amino acid polypeptide with calculated molecular weight of 65.7 kDa and
      theoretical pI of 6.28. The coding sequence of IbPPO was also directly amplified
      from the genomic DNA of sweetpotato that demonstrated that IbPPO was an intron
      free gene. The computational comparative analysis revealed that IbPPO showed
      homology to other PPOs of plant origin and contained a 50 amino acid plastidial
      transit peptides at its N-terminal and the two conserved CuA and CuB copper
      binding motifs in the catalytic region of IbPPO. A highly conserved serine-rich
      motif was firstly found in the transit peptides of plant PPO enzymes. Then the
      homology-based structural modeling of IbPPO showed that IbPPO had the typical
      structure of PPO: the catalytic copper center was accommodated in a central four
      helix bundle located in a hydrophobic pocket close to the surface. Finally, the
      results of the semi-quantitative RT-PCR analysis of IbPPO in different tissues
      demonstrated that IbPPO could express in all the organs of sweetpotato including:
      mature leaves, young leaves, the stems of mature leaves (petioles), the storage
      roots and the veins but at different levels. The highest-level expression of
      IbPPO was found in veins, followed by storage roots, young leaves and mature
      leaves; and the lowest-level expression of IbPPO was found in petioles. The
      present researches will facilitate the development of anti-brown sweetpotato by
      genetic engineering.

PMID- 17209429
TI  - [Isolation and characterization of a 2C-methyl-D-erythritol 2,4-cyclodiphosphate
      synthase gene from Taxus media].
AB  - 2C-methyl-D-erythritol 2,4-cyclodiphosphate (MEC) synthase (MECS, EC: 4.6.1.12)
      is the fifth enzyme of the nonmevalonate terpenoid pathway for isopentenyl
      diphosphate biosynthesis and further Taxol biosynthesis. The full-length MECS
      cDNA sequence (GenBank accession number DQ286391) was cloned and characterized
      for the first time from Taxus media, using Rapid Amplification of cDNA Ends
      (RACE) technique. The full-length cDNA of Tmmecs was 1081 bp containing a 741 bp
      open reading frame (ORF) encoding a peptide of 247 amino acids with a calculated
      molecular mass of 26.1 kDa and an isoelectric point of 8.97. Comparative and
      bioinformatic analyses revealed that TmMECS had extensive homology with MECSs
      from other plant species. Phylogenetic analysis indicated that TmMECS was more
      ancient than other plant MECSs. Southern blot analysis revealed that Tmmecs
      belonged to a small gene family. Tissue expression pattern analysis indicated
      that Tmmecs expressed constitutively in all tissues including roots, stems and
      leaves. The cloning and characterization of Tmmecs will be helpful to understand
      more about the role of MECS involved in the Taxol biosynthesis at the molecular
      level.

PMID- 17209430
TI  - [AFBN1 gene in patients with Marfan syndrome].
AB  - 30 exons have been analyzed using SSCP in patients with MFS or related
      phenotypes. We report 2 missense mutations occur in calcium-binding Epidermal
      Growth Factor-like (EGFcb) domains and 9 polymorphisms located both in coding and
      noncoding regions of FBN1 gene. Three intragenic microsatellite polymorphic
      markers MTS-1, MTS-2 and MTS-4 have been analyzed in patients with MFS and
      unrelated unaffected control individuals. We found significant differences in
      allele frequency distribution of MTS-2 and MTS-4 loci between MFS patients and
      unaffected individuals. Haplotype frequency distribution on normal and mutant
      chromosomes were significantly different. The most common haplotype was 2-11-8
      which was predominant on normal chromosomes of affected individuals. Haplotype 2
      2-8 was observed in 18% of cases on mutant chromosomes and in 4% of cases on
      normal chromosomes. These data demonstrate possibility and application of
      haplotype-segregation analysis with use of these intragenic markers for
      diagnostic purposes in affected families by Marfan's syndrome.

PMID- 17209431
TI  - [Molecular diagnosis and frequencies of primary hypolactasia in populations of
      RUSSIA and neighboring countries].
AB  - The digestion of the milk sugar (lactose) is observed every normal child but not
      in every adult. The decreased lactase synthesis in some adults results in
      problems with digestion of the whole milk (primary hypolactasy). An association
      of lactase activity in adults with carrying of the allele T within the
      polymorphism C/T-13910 located upstream of the lactase gene and 100% association
      of hypolactasy with the genotype C/C has recently been shown for a Finnish
      sample. In the present work we determined the LCT* C/T_13910 genotypes and allele
      frequencies in populations from Russia. The genotype C/C frequencies varied from
      36.6% for Russians to 88.2% for Chukchi and were close to the published medical
      and epidemiological data on hypolactasy frequencies in respective populations.
      Genotyping was performed by three different methods to identify the optimal one.
      Our results have shown that the studied locus is the key determinant for the
      primary hypolactasy development in various human populations. Consequently, the
      DNA diagnostics of the C/C genotype carrying is a promising predictive test to
      detect the primary hypolactasy long before its clinical development. Practical
      application of this type of diagnostics would be a step towards the individual
      oriented medicine.

PMID- 17209432
TI  - [Silencing of c-myc gene expression by enzymatically and chemically synthesized
      siRNAs].
AB  - Small interfering RNAs (siRNA) provide a powerful approach for sequence-specific
      silencing of gene expression. In the present study we investigated inhibition of
      c-myc gene expression by siRNAs targeted to the sequence 1452-1470 b. in third
      exon of c-myc mRNA and to homologous regions in second exons of c-myc (697-715
      b.) and N-myc (302-320 b.) mRNAs. siRNAs were prepared enzymatically according to
      the scheme, including dsDNA-templates preparation using Klenow fragment, separate
      in vitro transcription of each RNA strand with subsequent hybridization and
      removal of leader sequences by T1 RNase. Investigation of c-myc gene silencing by
      siRNAs revealed that enzymatically prepared siRNAs induce stronger inhibition of
      c-myc expression, than siRNA with the same sequence prepared by chemical
      synthesis. It was found that down-regulation of c-myc gene expression by
      investigated siRNAs results in efficient inhibition and even complete arrest of
      carcinoma cell proliferation, moreover, the extend of growth inhibition
      correlates with the level of siRNA-mediated reduction of c-myc mRNA.

PMID- 17209433
TI  - [Transcription TIMP3, DAPk1 and AKR1B10 genes in squamous cell lung cancer].
AB  - Lung cancer is one of the most frequent neoplasia in the Russia, the United
      States and Europe. This cancer is associated with functional activity changes of
      many genes. In the present study TIMP3, DAPK1 and AKR1B10 genes transcription
      analysis of squamous cell lung cancer specimens was carried out using reverse
      transcription-PCR. Substantial increasing of AKR1B10 transcription level is
      revealed in 80% tumor samples. TIMP3 and DAPK1 transcription level is
      considerably decreased in 76 and 72% tumor specimens, accordingly. These results
      may point out that all three genes are important for squamous cell lung cancer
      tumorogenesis while AKR1B10 is potential oncogene whereas TIMP3 and DAPK1 are
      potential tumor suppressor genes. We suggest that revealed substantial
      transcription level-changes of investigated genes may be used for
      oncodiagnostics.

PMID- 17209434
TI  - [Interactions of human 8-oxoguanine-DNA glycosylase with single- and double
      stranded DNA].
AB  - Interactions of human 8-oxoguanine-DNA glycosylase (hOGG1) with single- and
      double-stranded oligodeoxyribonucleotides (ODN) have been studied by the method
      of stepwise increase in ligand complexity. The ODNs have been found to inhibit
      the glycosylase-catalyzed reaction competitively. The K1 values have been
      determined for a set of ODNs. All units of non-specific DNA within the enzyme
      footprint have been shown to interact with the protein globule in an additive
      manner. An increase in the d(pN)n length (n) by one unit caused a monotonous 1.4
      1.5-fold increase in their affinity for the glycosylase ODN until n = 10, mostly
      due to weak nonspecific contacts of the enzyme and the sugar-phosphate backbone.
      The weak nonspecific additive interactions contributed about five orders of
      magnitude in the affinity of hOGG1 for specific DNA (Kd approximately 10(-5) M),
      whereas introduction of a 8-oxoguanine residue added about three orders of
      magnitude to this affinity (Kd approximately 10(-8) M). Quantitative features of
      recognition of specific DNA by the enzyme are analyzed.

PMID- 17209435
TI  - [Structural polymorphism of the liquid-crystalline dispersions formed from the
      double-stranded DNA molecules complexed with synthetic polycations].
AB  - The double-stranded, linear DNA molecules form the liquid-crystalline dispersions
      (LCD) in water-salt solutions containing positively charged polyconidin
      molecules. It was established from the analysis of the absorption spectra of the
      LCDs formed from (DNA-polyconidin) complexes, that the mean size of the particles
      of these dispersions is equal to -6000 angstroms. The small-angle X-ray data
      show, that in the LCD particles different density of packing of the (DNA
      polycation) complexes is realized. The comparison of the X-ray data of the liquid
      crystalline phases of (DNA-polyconidin) complexes formed under various conditions
      with the phase diagram, that reflects the polymorphism of the linear double
      stranded DNA liquid crystals, demonstrates that the hexagonal mode of the LCD
      packing is existing in 0.15-0.4 M NaCl solutions, whereas in 0.4-0.55 M NaCl
      solutions-- the cholesteric one. As a result of specific spatial organization the
      cholesteric LCD possesses of an abnormal optical activity in the CD spectrum. The
      similar situation takes place in the case of another synthetic polycation-
      poly(2,5-ionen), whose chemical structure differs from that of polyconidin. Thus,
      the structural polymorphism of the (DNA-polyconidine) LCDs was evidenced. It
      means that change of NaCl concentration opens a gate to control the spatial
      packing of the molecules of (DNA-polycation) complexes in the particles of LCDs.
      The supposition about mechanism of formation of the DNA cholesteric liquid
      crystalline state in the narrow interval of NaCl concentrations was suggested.

PMID- 17209436
TI  - [Improved efficient gene transfer into insect and mammalian cells by baculovirus
      vectors].
AB  - The fragments of genomics DNA of the nuclear polyhedrosis virus (NPV) containing
      genes of late viral proteins p10, p35, p39, were cloned, the promoter regions of
      this genes were used to design baculovirus transfer vectors. A double-promoter
      and triple-promoter baculovirus transfer vectors were obtained. Recombinant
      baculovirus vectors containing mammalian expression cassette with cytomegalovirus
      (CMV) promoter, the gene for green or red fluorescent protein, SV40pA and
      polylinker MCS were constructed for the delivery of foreign genes into mammalian
      cells.

PMID- 17209437
TI  - [Gene of mitochondrial DNA gamma-polymerase (POLG): frequency and linkage
      disequilibrium of two SNP's in Siberian populations].

PMID- 17209438
TI  - [Osteoporosis: modern approaches and new possibilities in the prevention and
      treatment].
AB  - Contemporary evidence-based approaches to the diagnostics, treatment, and
      prophylaxis of system osteoporosis (OP) are presented in the article. The main
      principles of therapeutic and preventive measures in OP are formulated. Bone
      tissue mineral density was studied with dual-energy x-ray absorptiometry using a
      QDR-4500A HOLOGIC osteodensitometer; the results and the authors' own experience
      in the application of pharmaceuticals was analyzed.

PMID- 17209439
TI  - [Pericardial diseases: actual issues of the diagnostics and treatment].

PMID- 17209440
TI  - [Diagnostics and treatment of the functional autonomy of the thyroid gland].
AB  - Functional autonomy of the thyroid gland (FATG) remains an important problem due
      to iodine deficiency over the whole territory of Russian Federation and the fact
      that iodine prophylaxis has not been conducted for a long period of time. Since
      iodine deficiency affects the thyroid gland (TG) as a whole, the formation of
      nodules is not limited to a single lobe, but leads to the development of
      multinodular goiter, the main feature of which is morphological and functional
      heterogeneity of TG tissue. Active cell proliferation in the iodine deficiency
      related goiter is associated with an elevated risk of somatic mutations,
      including activating mutations leading to thyrocyte functional autonomy.
      Diagnosis is often late due to the absence of any specific complaints in most
      patients. Hence, the pathology is often an accidental finding and is mostly
      revealed in patients with cardial diseases. For a long time, TG scintigraphy has
      been the only method allowing the diagnosis of FATG, while other techniques, such
      as ultrasonography and the measurement of the hormone levels in blood, only make
      it possible to assume the presence of this pathology. Nowadays, fine needle
      biopsy plays an important role since it gives a possibility to obtain direct cell
      level findings concerning the morphological structure of TG nodules and, in some
      cases, the functional condition of cells. Of late, great importance to clinical
      practice has been attached to new developments in FATG diagnostics,
      immunomorphological (immunocytochemical and immunohistochemical) techniques in
      particular. Most probably, new techniques of FATG verification will be based upon
      the study of TSHR as the specific marker of this pathology, and it will be
      possible to use immunocytochemical assay as an additional diagnostic method for
      the verification of autonomic nodular formations as early as right after the
      puncture.

PMID- 17209441
TI  - [Clinical manifestations of the expiratory tracheal stenosis, and its effects on
      the progress of bronchopulmonary pathology].
AB  - Non-differentiated connective tissue dysplasia (NDCTD) presents a genetic-related
      anomaly of the mesenchimal matrix leading to the dysfunction of various organs
      and systems, the degree of which determine the severity of the clinical picture
      as well as individual prognosis. Despite high prevalence, NDCTD is often
      neglected by practitioners because the clinical manifestations of this pathology
      are very polymorphic due to the fact that connective tissue (CT) is spread
      throughout the organism. Various changes in the skin, locomotor apparatus, and,
      especially, the internal organs determine the individual prognosis and cannot but
      influence the course of concomitant diseases. Among visceral NDCTD markers the
      most well-known ones are mesenchimal cardial dysplasias, such as valvular
      prolapses, false chords, interventricalar septum and Valsalva sinus aneurisms
      etc. However, the generalized CT defect in NDCTD implies the presence of
      polyorganic symptoms thus stimulating search for new visceral markers of CD
      dysplasia. Various internal manifestations of NDCTD, such as expiratory tracheal
      stenosis, have their own pathogenetic features, as well as specific clinical and
      functional manifestations.

PMID- 17209442
TI  - [Mortality risk factors in patients with chronic obstructive pulmonary disease].
AB  - The aim of this prospective study was to determine the mortality risk factors in
      patients with chronic obstructive pulmonary disease (COPD). Eighty-six COPD
      patients were observed during 3 to 5 years. The presence and the severity of COPD
      were established according to COPD criteria (1998). Unfavorable outcomes were not
      noted only in 39 (45.3%) of the patients. Nineteen patients died; among those 15
      patients died of the underlying disease and its complications. Death predictors
      in COPD may be listed as follows: forced expiratory volume in the 1st second is
      less than 40% normal value; SaO2 is less than 90%; the result of 6-minute walk
      test is less than 300 m; pulmonary arterial pressure is 40 mm Hg or higher; the
      thickness of the right ventricular (RV) wall is 0.7 cm or more; the volume of the
      RV cavity is 3.0 cm or more; the presence of relative right atrial dilation (the
      index of which is 0.9 or less); the presence of diastolic RV dysfunction;
      clinical symptoms of circulatory decompensation; a tendency towards the
      hyperkinetic type of circulation. The risk of death is higher in patients more
      than 60 years of age, those who have been experiencing dyspnea for more than 10
      years, patients who have been smoking for more than 40 years, and patients with a
      smoking index of 50 pack-year or higher.

PMID- 17209443
TI  - [Thrombus precursor protein (soluble monomeric protein) in patients with acute
      coronary syndrome].
AB  - The purpose of the study was to determine the level of thrombus precursor protein
      (TrP) in patients with acute coronary syndrome (ACS). Twenty-six patients with
      ACS and anginal pain experienced during 2 to 12 hours (7.2 +/- 1.3 hours),
      admitted to cardiological intensive care unit, were enrolled in the study. Five
      ml of blood were sampled from a cubital vein of all the patients during the phase
      of the most intensive pain. TrP blood levels were measured with ELISA, Enzyme
      Linked Immunoadsorbent Assay. The control group consisted of 29 healthy
      volunteers and 22 patients with stable exertional stenocardia. A significant
      increase in TpR (7.2 +/- 1.45 mcg/ml) was noted in the ACS patients as early as
      during the first 6 hours, vs. the healthy controls (1.01 +/- 0.12 mcg/ml) and the
      patients with stable stenocardia (1.21 +/- 0.06 mcg/ml), p < 0.01. A high level
      of TrP in the ACS patients could be noted earlier than a diagnostically
      significant increase in creatine phosphokinase level. No direct correlation was
      observed between the TrP level and the dynamics of such indices of the
      procoagulatory hemocoagulation chain as fibrinogen, prothrombin index, and active
      partial thromboplastin time. The results of the study demonstrate that the
      measurement of TrP level is highly informative when the intensity of
      intravascular blood coagulation in ACS patients is to be evaluated, which can be
      used to clarify indications to anticoagulation therapy. The enzyme immune method
      of TrP detection in the plasma of ACS patients can be recommended for clinical
      application.

PMID- 17209444
TI  - [The effects of intracoronary infusion of bone marrow mononuclears on myocardial
      contractility].
AB  - The effects of intracoronary infusion of bone marrow mononuclears (BMM) on
      myocardial contractility after myocardial infarction (MI) was studied in 16 post
      infarction patients. The intracoronary infusion of autologic BMM during the
      subacute period of MI did not have a significant effect on myocardial
      contractility, the functional class of chronic heart failure, physical tolerance,
      and quality of life evaluated three and six months after the transplantation.
      Intracoronary BMM transplantation did not provoke ventricular tachycardia or
      ventricular fibrillation. BMM transplantation into an infarcted myocardium did
      not exacerbate coronary heart disease in post-infarction patients.

PMID- 17209445
TI  - [The functional condition of the left ventricle in patients suffering from
      rheumatoid arthritis with subcutaneous rheumatoid nodules].
AB  - The purpose of the study was to evaluate the systolic and diastolic left
      ventricular (LV) function in patients with the system form of rheumatoid
      arthritis (RA) with subcutaneous rheumatoid nodules (SRN). The subjects, 105
      patients with proved RA, were divided into two groups. The main group consisted
      of 40 patients suffering from system RA with SRN. The comparison groups included
      40 patients suffering from the articular-and-visceral form of RA without SRN, and
      25 patients with the articular form of RA. The systolic LV function was evaluated
      in all the 105 RA patients using M-mode Echo CG. In 20 patients with SRN systolic
      and diastolic LV function was evaluated with radionuclide ventriculography (RVG).
      The hemodynamic parameters obtained with Echo CG and RVG were processed according
      to variation statistics rules, presenting the data in groups as a mean and the
      standard error (M +/- m); the results were compared between the patients and
      between the patients and healthy controls. The significance was estimated using
      Student criterion (p < 0.05). In the group of RA patients with SRN, Echo CG and
      RVG found a significant decrease in LV systolic function parameters vs. patients
      without SRN and healthy controls. RVG revealed LV diastolic dysfunction in RA
      patients with SRN. Systolodiastolic LV dysfunction in these patients suggests
      myocardial involvement. Present-day instrumental methods of the evaluation of
      functional heart condition may be used to evaluate systolic and diastolic LV
      function in RA patients, especially during the dynamic observation of the
      effectiveness of RA treatment with modern anti-rheumatic preparations.

PMID- 17209446
TI  - [Apoptosis of peripheral blood mononuclears and evaluation of the effectiveness
      of antiviral therapy of chronic C hepatitis].
AB  - The effects of combined antiviral therapy on the apoptosis of peripheral blood
      mononuclears (PBM) were investigated in 54 patients with chronic hepatitis C
      (CHC), including patients with chronic viral-and-alcohol hepatitis (CVAH).
      Simultaneously, serum concentrations of cytokines (tumor necrosis factor-alpha
      (TNF-alpha), interferon-gamma (IFN-gamma), and interleukins 10 and 12) using flow
      cytofluorimetry were taken. The results demonstrate an increase in the intensity
      of PBM apoptosis in patients with CHC and CVAH vs. controls; there was a tendency
      of lesser apoptosis intensity in the CVAH subgroup. In both groups IFN-gamma and
      TNF-alpha concentrations were increased, and there was a direct correlation
      between the level of apoptosis and TNF-alpha concentration. The study found an
      increase in the intensity of apoptosis in CHC patients with primary virological
      response to antiviral therapy with IFN-alpha and riboflavin, which can be
      considered an additional prognostic factor of the effectiveness of treatment.

PMID- 17209447
TI  - [Psychovegetative disturbances in patients with chronic non-calculous
      cholecystitis combined with chronic opisthorchosis].
AB  - A complex clinico-instrumental, laboratory and psychological examination of 122
      patients with chronic non-calculous cholecystitis (CNCC), 63 of who had chronic
      opisthorchosis (CO), was conducted. The controls were 33 healthy individuals.
      Patients with CNCC and CO had hypomotoric dyskinesia, Oddi's sphincter
      dysfunction, higher levels of personal anxiety and depression more often than
      others.

PMID- 17209448
TI  - [Free radical peroxidation processes and cardiotoxicity in treatment of malignant
      lymphomas].
AB  - The dynamics of free radical and peroxidation processes in patients with non
      Hodgkin lymphomas (NHL) was studied parallel to the evaluation of changes in the
      functional condition of the cardiovascular system during a course of
      chemotherapy. Thirty-one patients (17 men; 14 women) aged 30 to 81, were
      examined. The dynamics of active oxygen forms (AOF) generation was studied using
      chemiluminiscent technique. The intensity of leucocyte chemiluminiscence (CL)
      (basal and zimozan-stimulated ones), the blood level of malonic dialdehyde, the
      antiperoxidation blood plasma activity according to its hydrogen peroxide-induced
      CL intensity, were measured. The functional condition of the cardiovascular
      system was evaluated using ECG, EchoCG, and Holter monitoring. The study revealed
      an increase in AOF generation by leucocytes, which correlated with the severity
      of the disease. The treatment of the NHL patients with cytostatics was associated
      with the activation of free radical reactions, which was maximal during the first
      24 hours 1 hour after drug administration. Cytostatic therapy was characterized
      by a cardiotoxic effect, which consisted in an increase in the rate of various
      arrhythmias and a decrease in the heart contractility. The study demonstrates a
      direct correlation between the degree of AOF generation growth and the prominence
      of myocardial lesion signs. The authors conclude that the intensification of free
      radical reactions under the conditions of cytostatic therapy causes cardiotoxic
      effects, which requires a course of preventive cardioprotective therapy before
      chemotherapy is commenced.

PMID- 17209449
TI  - [Thyroid gland alterations in Perm region residents as observed by means of
      ultrasonography].
AB  - Thyroid gland (TG) ultrosonography, performed in 2000 residents of Perm region
      (370 men and 1630 women aged 18 to 84 years), showed that only 1/3 of the
      subjects had no TG abnormalities. Despite mass iodine prophylaxis, resumed in
      Perm more than 6 years ago, and group iodide prophylaxis that is being actively
      introduced at present, the prevalence of goitre has not decreased. On the
      contrary, it has risen from 26.3% to 42.3% in Perm region since 90-s. Nodules
      were found in one out of five subjects. TG diseases were significantly more
      frequent in women than in men. The majority of the subjects had no complaints,
      and any abnormality, including TG cancer (6 cases), was found by chance. The
      reduction of TG size with age is not typical of Perm population, and the increase
      of TG volume in the elderly (both men and women) is due to TG nodules formation.
      Thus, preventive ultrasonography should be introduced widely in order to reveal
      TG abnormalities at early stages, not only among the population of iodized
      regions, but also in ecologically unfavourable ones. This diagnostic test must
      become a necessary procedure in preventive examinations of people exposed to
      occupational hazards.

PMID- 17209450
TI  - [Experience in application of various antidepressants in gerontology].
AB  - The article presents data on the effectiveness of comorbide therapy with
      amlodipine and antidepressants of various groups in patients more than 65 years
      old suffering from coronary artery disease (CAD), arterial hypertension (AH), and
      comorbide depression. Eighty-eight patients with stable FC I-III stenocardia,
      accompanied by AH and comorbide depression, were examined. The patients were
      divided into three groups. Patients in group I (n = 21) received amlodipine
      therapy in a dose of 2.5 to 5 mg/day with amitriptyline in a dose of 25 mg/day.
      Group II patients (n = 25) received tianeptine in a dose of 25 mg/day in addition
      to amlodipine in a dose of 2.5 to 5 mg/day. Group III patients (n = 20) were
      treated with a combination of amlodipine 2.5 to 5 mg/day with sertraline in a
      dose of 50 mg/day. The comparison group consisted of 22 patients who received
      monotherapy in a dose of 2.5 to 5 mg/day. The study revealed that all these
      combinations with different antidepressants significantly lowered the average
      depression score and significantly improved the quality of life, unlike
      amlodipine monotherapy. The best combination was amlodipine plus tianeptine,
      which did not only demonstrate antidepressive and anxiolytic effects, but also
      led to improvement in prognostically significant parameters of cardiac rhythm
      variability in elderly patients with comorbide depressive disorders underlied by
      stable stenocardia and arterial hypertension.

PMID- 17209451
TI  - [Diagnostics and treatment of traumatic myocardial infarction].
AB  - The authors describe their own clinical observations of four patients with acute
      chest injury, who developed myocardial infarction due to traumatic dissection of
      anterior interventricular artery intima and a subsequent thrombosis of the
      artery. The authors adduce clinicolaboratory characterization of traumatic
      myocardial infarction and describe early and long-term (three years) results of
      transcutaneous coronary operations (balloon angioplasty and stenting) performed
      in these patients.

PMID- 17209452
TI  - [On the strategy of treatment of atrial fibrillation in the elderly (a response
      to the article "Ciliary arrhythmia" by M. A. Gurevich)].

PMID- 17209453
TI  - [Localization of active hydrogen ions in the gastric mucosa].

PMID- 17209454
TI  - [Anxiogenic and mnestic effects of corticoliberin and its analogs introduced into
      the brain ventriculi of rats].
AB  - The behavioral effects of native human corticotropin-releasing hormone (CRH) and
      its agonists D-Glu-20 (R1) and D-Pro-5 (R2) introduced (0.01 - 1 microg) into the
      lateral brain ventriculi of Sprague-Dowley rats have been studied in the open
      field, dark - light, Y-maze, and place preference tests. The different effects of
      CRH and its agonists on the anxiety level and short-term memory were revealed. D
      Glu-20 (an R1 agonist of CRH) acted as an anxiogen in the open field and dark -
      light tests. D-Pro-5 (an R2 agonist of CRH) did not cause the typical anxiogenic
      effect, but produced a nonspecific suppression of behavior. D-Pro-5 only in high
      doses decreased the number of visits into the light box in the dark - light test.
      At the same time, this compound enhanced the short-term memory to a maximum
      degree and prevented the memory loss induced by diazepam. The data obtained are
      in agreement with the published data about differential participation of R1 and
      R2 receptor systems of CRH in the regulation of emotional and mnestic components
      of behavior. The anxiogenic action of CRH is connected with the activation of R1
      receptors of CRH.

PMID- 17209455
TI  - [The influence of ecdysteroid fraction from Serratula coronata on transmembrane
      ionic currents of snail neurons].
AB  - Changes of the transmembrane potassium, calcium, and sodium ion currents in
      isolated neurons of Lymnaea stagnalis snail under the action of ecdysteroid
      fraction (serpisten) from Serratula coronata L. applied from outside in 0.01 
      1000 microg/ml concentrations have been studied using the voltage-clamp
      technique. It is established for the first time that serpisten non-selectively
      activates the potassium and calcium ion currents (the currents amplitude
      increases by 2 - 15%) and reduces nonspecific membrane leakage currents in the
      entire range of concentrations. The sodium ion current also increased by 4 - 7%
      under the action of Serpisten in low concentrations (0.01 -10 microg/ml) in
      comparison with control, but this current decreased by 5 -10% at serpisten
      concentrations of 100 and 1000 microg/ml. The effects were reversible. The
      kinetics of currents was not changed under the action of serpisten.

PMID- 17209456
TI  - [Comparative study of the effects of melatonin and epitalon on the protracted
      memory under the shuttle labyrinth test conditions in rats in the course of
      aging].
AB  - The influence of the chronic administration of melatonin (epiphyseal hormone) and
      epitalon (a synthetic tetrapeptide increasing melatonin production) on the
      learning process and the protracted memory has been studied in LIO rats in the
      course of aging for 2 years under standard illumination regime (12L :12D). The
      daily administration of melatonin (Sigma, USA) with drinking water (in 10
      mg/liter dose at night) in rats beginning with the age of 4 months did not
      influence the learning processes in young and adult animals but it was found to
      contribute to optimization of the brain cognitive function in rats in the course
      of aging, by improving the protracted memory process. Epitalon administered in a
      daily dose of 0.1 microg per animal beginning with the age of 4 months showed
      mnemotropic properties (decreasing the extent of memory disorders) in old rats
      under conditions of the shuttle labyrinth test.

PMID- 17209457
TI  - [Effects of melatonin and motherwort tincture on the emotional state and visual
      functions in anxious subjects].
AB  - The chronic administration of melatonin (0.75 mg at night, 10 days) led to a
      significant decrease in the thresholds of retinal brightness sensitivity and
      improved the emotional state in anxious young subjects. Analogous changes were
      less pronounced after the treatment with common motherwort (Leonurus cardiaca)
      tincture. It is suggested that there is a relation between the limitation of
      anxiety and the improvement of visual function (sensitivity).

PMID- 17209458
TI  - [Influence of the selective ligands of dopamine and 5-hydroxytryptamine receptors
      on the tolerance to global cerebral ischemia].
AB  - Selective dopamine (D) receptor agonists either slightly improve (D2 and D3) or
      do not affect (D1 and D4) the tolerance of the brain to global ischemia. As for D
      and 5-HT (hydroxytryptamine) antagonists, only D1 antagonist SCH 23390 and 5-HT2
      antagonist ketanserin produce a small neuroprotective effect, while D2, D4, 5
      HT(2B) and 5-HT(2C) antagonists are not active. Simultaneous injection of D2
      (raclopride), D3 (GR 103691), and D4 (L 745870) receptor blockers also does not
      protect the brain. These results are not at variance with a widespread hypothesis
      that the accumulation of extracellular 5-HT and especially D in the brain causes
      the neuron damage. The effect of ketanserine is not increased by D2 or D4
      blockers, but the introduction of D3 blocker GR 103691 (+88%) and especially the
      simultaneous injection of D2,3,4 antagonists improve the effect of ketanserine
      (+134%). The neuroprotective effect of the last combination is not lower but even
      exceeds that of some neuroleptics. This fact shows the possibility to increase
      the tolerance to cerebral ischemia by simultaneously blocking D and 5-HT
      receptors.

PMID- 17209459
TI  - [Experimental evaluation of the effect of glycine and its phosphorylated
      derivative on ischemic brain injury].
AB  - The effect of glycine and its phosphorylated derivative (AKF 90-7) on the
      ischemic brain injury in experimental animals has been studied. The therapeutic
      injection of glycine and AKF 90-7 (50 100 mg/kg) increased the survival of
      laboratory animals under the conditions of ischemia caused by ligation of the
      carotid artery. In a dose of 50 mg/kg, AKF 90-7 was more effective than glycine
      in activating enzymes of the antioxidant system and preventing the formation of
      lipid peroxidation products.

PMID- 17209460
TI  - [Efficacy of cerebrolysin in cerebral hemorrhage model in rats].
AB  - The pharmacological efficacy of cerebrolysin (a brain-derived peptidergic drug)
      was studied in rats with a unilateral hemorrhagic stroke model. Cerebrolysin
      produces a neuroprotective effect, which is manifested by a decrease in the
      number of degenerated neurons in the vicinity of hematoma region in acute period
      and by a reduction of the neuronal loss in the early recovery phase. Besides, the
      administration of cerebrolysin improves the functional state as judged from the
      results of neurological and behavioral tests (open field, paw licking, and
      passive avoidance). A decrease in the hyperactivity in the open field test and
      the conservation of latent avoidance in the passive avoidance test demonstrate
      the drug influence on the maintenance of inhibitory processes deteriorated in
      stroke.

PMID- 17209461
TI  - [The mechanism of antiarrhythmic action of a new ammonium derivative of lidocaine
      (LKhT-12-02)].
AB  - The results of electrophysiological investigation of the effects of LKhT-12-02 (a
      quaternary ammonium derivative of lidocaine) on the intact cat heart and the
      isolated ion channels of Lymnaea stagnalis snail showed that this compound
      belongs to class 1B antiarrhythmic agents (Vaughan - Williams classification).
      The drug does not suppress the automatic nonmonotonic rhythm driver, does not
      influence the conductance in ventricles, auricles, and atrioventricular node in
      the sinus rhythm, and does not elongate the effective refractory period of the
      auricles and atrioventricular node. LKhT-12-02 decreases the rate of fast
      depolarization of the action potential, while not reducing its duration. The
      compound does not influence the conduction of sodium ion channels.

PMID- 17209462
TI  - [The effect of cichorium root extract on the morphofunctional state of liver in
      rats with carbon tetrachloride induced hepatitis model].
AB  - It is established that cichorium root extract therapy leads to normalization of
      some morphofunctional liver features (decreases glycogen content and cell of
      necrosis and increases the number of cells with pronounced protein synthesis
      activity) in rats with CCl4-induced hepatitis.

PMID- 17209463
TI  - [Immunostimulant properties of polyoxidon on the model of acute poisoning with
      anticholinesterase chemicals in rats].
AB  - Experiments on noninbred rats showed that, upon acute poisoning with toxic
      chemicals (sarin, VX agent; 1.0 LD50) and the treatment with atropine (10 mg/kg),
      the administration of polyoxidon in a daily dose of 100 mg/kg over 4 days partly
      reduces the degree of immune system suppression and the level of lipid
      peroxidation induced by toxic chemicals.

PMID- 17209464
TI  - [The influence of experimental therapy on the dynamics of endogenous glucosamine
      content in laboratory animals with nephropathy].
AB  - The effects of glucosamine hydrochloride, glucosamine sulfate, N
      acetylglucosamine, glucosamine pentaacetate, and combinations of glucosamine
      hydrochloride and N-acetylglucosamine with diclofenac sodium on the endogenous
      glucosamine (aminosugar) content in the blood and kidney of rats with
      experimental nephropathy have been studied. The development of inflammatory and
      destructive processes in kidneys is accompanied by an increase in the aminosugar
      content in the blood serum and the corresponding decrease in renal tissues. This
      fact can be used as a nonspecific diagnostic criterion for the level of kidney
      damage and for the efficacy of pharmacotherapy. Normalization of these indices in
      the case of successful therapy was observed, which was most pronounced upon the
      administration of glucosamine hydrochloride, N-acetylglucosamine, and their
      combinations with diclofenac sodium.

PMID- 17209465
TI  - [Current problems in geriatric psychopharmacotherapy].

PMID- 17209466
TI  - [Anticoagulant activity of sulfated polysaccharides].
AB  - The paper reviews published data on the chemical structure of sulfated
      polysaccharides of animal, plant, and microbial origin as well as synthetic or
      semi-synthetic derivatives, and on the anticoagulant activity of these compounds
      in vitro and in vivo. The influence of sulfated polysaccharides on the plasma and
      cell hemostasis links is considered. Relationships between the structure and
      activity and the mechanisms of action are discussed.

PMID- 17209467
TI  - [The cholinergic system of lymphocytes].
AB  - The role of acetylcholine and the cholinergic system in non-neuronal cells (in
      particular, in lymphocytes) in humans is considered. Lymphocytes express most of
      the cholinergic components found in the nervous system, which makes possible
      acetylcholine-dependent stimulation of lymphocytes in the spleen and lymph nodes.
      The sympathetic innervation and paracrine mediators control several immune cell
      functions, the blood perfusion, lymphoid cells and antigen uptake by the lymphoid
      organs. Cholinergic compounds can influence the immune system through the CNS
      (via hypothalamic - pituitary - adrenal axis), the autonomoic nervous system,
      and/or an independent non-neuronal cholinergic system in lymphocytes. The
      dysfunction of the non-neuronal cholinergic system plays a certain role in the
      pathogenesis of many diseases. Experiments revealed the possibility to modulate
      some effects of non-neuronal acetylcholine in the prevention of stress-induced
      ulcers and anaphylactic shock. This could provide a basis for the development of
      new therapeutic strategies to target the non-neuronal cholinergic system.

PMID- 17209468
TI  - [Doping in sports].
AB  - Drugs used by athletes for the improvement of results are described and
      classified with respect to chemical structure and pharmacological action. The
      main groups of drugs treated as doping are considered and the WADA requirements
      to prohibited preparations are formulated. The main effects produced by drugs on
      the athletes and animals (race horses, fight dogs, etc ) are described and the
      measures of therapy against side effects are outlined.

PMID- 17209469
TI  - Carotenoid content and flesh color of selected banana cultivars growing in
      Australia.
AB  - BACKGROUND: The problems of vitamin A deficiency and chronic diseases have
      emerged in recent years in some countries in the Micronesian region. These
      problems are associated with the dietary shift towards imported processed foods
      and lifestyle changes. Research in the Federated States of Micronesia indicates
      that yellow- and orange-fleshed banana cultivars contain significant levels of
      provitamin A carotenoids. OBJECTIVE: To identify further banana cultivars that
      may be promoted to alleviate vitamin A deficiency among children and women and
      chronic disease problems among adults. METHODS: Ripe fruit of banana cultivars
      growing in Australia (sourced mostly from a field research collection) were
      assessed for carotenoid content and flesh color. Ten cultivars with yellow or
      yellow/orange flesh color (including common cultivars of Southeast Asia and the
      Pacific Islands) were selected and compared with two cream-fleshed cultivars,
      including Williams, of the Cavendish group, the most commonly marketed banana
      worldwide. Carotenoid content was analyzed by high-performance liquid
      chromatography (HPLC). Flesh color was analyzed by HunterLab colorimetry.
      RESULTS: The yellow/orange-fleshed Asupina (a Fe'i banana) contained the highest
      level (1,412 microg/100 g) of trans beta-carotene, the most important provitamin
      A carotenoid, a level more than 20 times higher than that of Williams. All 10
      yellow or yellow/orange-fleshed cultivars (Asupina, Kirkirnan, Pisang Raja, Horn
      Plantain, Pacific Plantain, Kluai Khai Bonng, Wain, Red Dacca, Lakatan, and
      Sucrier) had significant carotenoid levels, potentially meeting half or all of
      the estimated vitamin A requirements for a nonpregnant, nonlactating adult woman
      within normal consumption patterns. All were acceptable for taste and other
      attributes. The cream-fleshed cultivars had minimal carotenoid levels. There was
      a positive significant correlation between carotenoid content and deeper
      yellow/orange coloration indicators. CONCLUSIONS: These yellow- or yellow/orange
      fleshed carotenoid-rich banana cultivars should be considered for promotion in
      order to alleviate vitamin A deficiency and chronic disease in susceptible target
      communities and to provide variety and enjoyment as exotic fruits in both
      developing and industrialized countries.

PMID- 17209470
TI  - Iodine deficiency persists in the Zanzibar Islands of Tanzania.
AB  - BACKGROUND: Iodine is an essential micronutrient for normal human growth and
      development. It is estimated that more than 1.6 billion people live in iodine
      deficient environments, yet there are still some countries and areas where the
      prevalence of iodine-deficiency disorders is unknown. OBJECTIVE: To establish the
      prevalence of iodine-deficiency disorders in the Zanzibar Islands, a community
      assumed to have ready access to iodine-rich seafoods. METHODS: In a cross
      sectional study, 11,967 schoolchildren were palpated for goiter prevalence, a
      subsample was evaluated for urinary iodine concentration, and the availability of
      iodated salt was assessed at the household and retail levels. RESULTS: The mean
      total goiter prevalence was 21.3% for Unguja and 32.0% for Pemba. The overall
      median urinary iodine concentration was 127.5 microg/L. For Unguja the median was
      185.7 microg/L, a higher value than the median of 53.4 microg/L for Pemba (p <
      .01). The household availability of iodated salt was 63.5% in Unguja and 1.0% in
      Pemba. The community was not aware of the iodine-deficiency problem and had never
      heard of iodated salt. CONCLUSIONS: The inadequate intake of iodine documented in
      the Zanzibar Islands belies the common assumption that an island population with
      access to seafood is not at risk for iodine-deficiency disorders. We urge health
      planners to implement mandatory salt iodation and education efforts to alleviate
      the situation.

PMID- 17209471
TI  - The association between stunting and overweight in Latin American and Caribbean
      preschool children.
AB  - BACKGROUND: Although some segments of the population continue to suffer from
      undernutrition, other groups exhibit excess weight gain, resulting in the
      coexistence of undernutrition and obesity and leading to a dual nutritional
      burden. OBJECTIVE: To explore the association between stunting and overweight in
      preschool children from Latin American and Caribbean countries. METHODS: We
      analyzed cross-sectional data from children 0 to 5 years of age from 79
      nationally representative surveys, compiled by the World Health Organization
      (WHO) Global Database on Child Growth and Malnutrition. This database defines
      stunting as low height-for-age and overweight as high weight-for-height. These
      variables were explored with the use of simple and multiple regression models.
      RESULTS: There were significant differences between subregions in the prevalence
      of stunting: the prevalence was 7.4% in the Caribbean, 11.3% in South America,
      and 20.4% in Central America (p < .001). In contrast, the estimated prevalence of
      overweight was similar between subregions. The overall prevalence rates of
      stunting and overweight in Latin America and the Caribbean in the year 2000 were
      13.7% and 4.3%, respectively. We found an inverse relationship (r = -0.3) between
      the prevalence rates of overweight and stunting, overall and within subregions.
      South America exhibited the highest slope and intercept on the regression of
      overweight on stunting. CONCLUSIONS: Different subregions of Latin America and
      the Caribbean have different prevalence rates of childhood stunting but similar
      prevalence rates of overweight. There is an inverse relationship between stunting
      and overweight. The South American subregion had the highest increase and
      prevalence of overweight of the Latin American region.

PMID- 17209472
TI  - Traditional cooked vegetable dishes as important sources of ascorbic acid and
      beta-carotene in the diets of Indian urban and rural families.
AB  - BACKGROUND: Fresh vegetable produce is abundant during the winter season in
      Punjab. It is an important source of vitamins and minerals in the Punjabi diet,
      but the availability of ascorbic acid and beta-carotene from the vegetables is
      altered to varying degrees when they are subjected to traditional household
      processing methods. OBJECTIVE: To determine the importance of traditional cooked
      vegetable dishes as sources of ascorbic acid and beta-carotene among urban and
      rural families during the winter. METHODS: Information about vegetable
      consumption, storage, and cooking practices was collected from 60 families, 30
      each from urban and rural areas of Ludhiana District, Punjab, India. Samples of
      the common cooked vegetable dishes were prepared in the laboratory by methods
      ascertained from the survey and analyzed for ascorbic acid and beta-carotene.
      RESULTS: The average total daily per capita consumption of vegetables by urban
      and rural families was 411.7 and 365.9 g, respectively. Cooked vegetable dishes
      provided 68.7% of the total vegetable intake for urban families and 85.0% for
      rural families. On average, the edible portion constituted 78.9% of the weight of
      the vegetables. Ten cooked vegetable dishes that were most frequently consumed by
      the families (mustard saag, potato-spinach, potato-fenugreek, potato-brinjal,
      potato-cauliflower, potato-capsicum, potato-carrots, potato-beans, potato-peas,
      and cabbage-peas) were selected for preparation in the laboratory and nutritional
      analysis. The average concentrations of ascorbic acid and beta-carotene in the
      cooked vegetable dishes were 46.0 mg/100 g and 794.2 microg/100 g fresh weight,
      respectively. The percentage losses of ascorbic acid and beta-carotene during
      preparation and cooking were 26.1% and 25.9%, respectively. CONCLUSIONS: For
      adult Indian men and women, the recommended dietary allowance of ascorbic acid is
      40 mg, and that of beta-carotene is 2,400 microg. Cooked vegetable dishes
      provided 269.9% and 77.5% of the recommended dietary allowances of ascorbic acid
      and beta-carotene, respectively, indicating that these dishes are good sources of
      these nutrients in the diets of both urban and rural families during the winter
      season.

PMID- 17209473
TI  - Prevalence of anemia among pregnant women and adolescent girls in 16 districts of
      India.
AB  - BACKGROUND: Nutritional anemia is one of India's major public health problems.
      The prevalence of anemia ranges from 33% to 89% among pregnant women and is more
      than 60% among adolescent girls. Under the anemia prevention and control program
      of the Government of India, iron and folic acid tablets are distributed to
      pregnant women, but no such program exists for adolescent girls. OBJECTIVE: To
      assess the status of anemia among pregnant women and adolescent girls from 16
      districts of 11 states of India. METHODS: A two-stage random sampling method was
      used to select 30 clusters on the basis of probability proportional to size.
      Anemia was diagnosed by estimating the hemoglobin concentration in the blood with
      the use of the indirect cyanmethemoglobin method. RESULTS: The survey data showed
      that 84.9% of pregnant women (n = 6,923) were anemic (hemoglobin < 110 g/L);
      13.1% had severe anemia (hemoglobin < 70 g/L), and 60.1% had moderate anemia
      (hemoglobin > or = 70 to 100 g/L). Among adolescent girls (n = 4,337)from 16
      districts, the overall prevalence of anemia (defined as hemoglobin < 120 g/L) was
      90.1%, with 7.1% having severe anemia (hemoglobin < 70 g/L). CONCLUSIONS: Any
      intervention strategy for this population must address not only the problem of
      iron deficiency, but also deficiencies of other micronutrients, such as B12 and
      folic acid and other possible causal factors.

PMID- 17209474
TI  - Characteristics attributed to complementary foods by caregivers in four countries
      of Latin America and the Caribbean.
AB  - BACKGROUND: Attributes that caregivers assign to complementary foods have been
      primarily described in the context of illness, but attributes assigned to foods
      in everyday circumstances must be understood to effectively promote good
      complementary feeding. OBJECTIVE: This study aimed to understand how mothers
      judge complementary foods to be appropriate by cross-cultural examination of food
      perceptions in four different Latin American and Caribbean countries. METHODS: We
      used semistructured interviews to assess attributes that mothers ascribed to a
      list of key foods, both home-made and manufactured, and reasons for feeding or
      not feeding them. We elicited attributes from 79 caregivers with children 6 to 24
      months of age from two urban and perirban sites each in Brazil, Jamaica, Mexico,
      and Panama. RESULTS: Textual analysis based on six home foods common to the four
      countries and manufactured foods resulted in six attribute categories, five of
      which could be positive or negative (Nutrient Content, Effects on Child, Child's
      Response, Availability and Accessibility, and Other Food Attributes); one (Food
      Quality and Safety) was only negative. Analysis of attributes of home foods
      (chicken, eggs, beans, carrots, bananas or plantains, and oranges) revealed many
      beliefs that were common within and across countries, whereas analysis of the
      attributes of manufactured foods revealed that these foods were less known.
      CONCLUSIONS: The consistency of the attribute categories across countries and
      across home and manufactured foods suggests their relevance to planning programs
      to improve complementary feeding in Latin America and the Caribbean and possibly
      other developing countries. These results can be used programmatically to assess
      the need for and the focus of food education programs, and to indicate which
      countries will be more receptive to certain foods as a means of improving
      complementary feeding.

PMID- 17209475
TI  - Weaning foods and their impact on child-feeding practices among low-income
      Nigerian mothers.
AB  - BACKGROUND: Many children in rural communities of developing countries die of
      nutrition-related causes due to lack of nutrition education and low purchasing
      power of the families, which result in low-quality weaning foods and poor feeding
      practices. OBJECTIVE: To evaluate the nutritional composition of local weaning
      foods and their impact on child feeding practices among low-income Nigerian
      mothers. METHODS: A cross-sectional survey was conducted between March and June
      2005 among 294 randomly selected pairs of nursing mothers and their children who
      attended the postnatal clinic of State Specialist Hospital and Comprehensive
      Health Centers in Akure community, Ondo State, Nigeria. A structured, self-or
      interviewer-administered questionnaire was used to collect information on infant
      demographic characteristics, feeding, and socioeconomic characteristics of the
      parents. The children's weights were recorded, and samples of the weaning foods
      were analyzed. RESULTS: The mothers' ages ranged from 22 to 37 years, and the
      children's from one to 12 months. Among the parents, two-fifths of the
      respondents worked as drivers, mechanics, carpenters, and the like, while the
      remaining respondents were civil servants, health professionals, teachers,
      merchants, and housewives. The educational attainment of the parents ranged from
      no formal education (1.4%) to higher education (46%); 13% had completed primary
      school, and 39.6% had completed secondary school. The average monthly family
      income was between 3,500 and 30,000 naira (US dollar 23.3-dollar 200). Among the
      children, 58.3% were of normal weight, 41.1% were mildly underweight, 0.3%
      moderately underweight, and 0.3% severely underweight; 23.1% were exclusively
      breastfed, 9.5% received breastmilk and traditional medicinal herbs, 15.6%
      received breastmilk and commercial weaning food, 7.4% received commercial weaning
      food only, 14.8% received local weaning foods only, 24.1% received local weaning
      foods plus breastmilk, and 5.8% received the family diet. CONCLUSIONS: We found
      that a high proportion of the nursing mothers used local ingredients to formulate
      weaning foods for their babies. The nutritional compositions of these foods is of
      high quality and are suitable as weaning foods, particularly for infants of low
      income parents who do not have access to commercial weaning foods.

PMID- 17209476
TI  - Econutrition: implementation models from the Millennium Villages Project in
      Africa.
AB  - Econutrition integrates environmental health and human health, with a particular
      focus on the interactions among the fields of agriculture, ecology, and human
      nutrition. Soil loss and degradation and human undernutrition are major barriers
      to economic development in Africa. A primary aim of the Millennium Villages
      Project in Africa is to meet the Millennium Development Goals by integrated
      multisectoral interventions in health and nutrition, agriculture, and
      environmental sustainability in hunger and poverty hot spots in Africa.
      Econutrition is only one example of how interdisciplinary approaches are not only
      critical to alleviating extreme poverty but also fundamental to linking basic
      science understanding in multiple areas. Human health and agricultural
      productivity gain, and the costs of the gains are lowered, when we take the
      opportunity to apply different disciplines through cross-sectoral, thematically
      linked interventions.

PMID- 17209477
TI  - Good governance for nutrition in the Philippines: elements, experiences, and
      lessons learned.
AB  - Malnutrition is a multifactorial problem that needs a multisectoral solution.
      This article reviews the role of good governance in nutrition programs, citing
      the Philippines as an example. In the Philippines, these efforts are reflected in
      the partnership between the public and private sectors in the establishment of
      the country's capability in research, policy-making, and program implementation.
      The establishment of the different public institutions engaged in research and
      policy-making is discussed, highlighting the role of political will through
      legislation. The evolving tasks of the nutrition program are discussed by citing
      the tasks in two eras. In the 1970s, the challenges were limited national
      nutrition data, man-power, tools, and health infrastructure. The public and
      private institutions were able to respond by legislating national nutrition
      surveys and dedicated nutrition workers in each village. The challenges in the
      current era are improved implementation of health programs, given the devolution
      of health services, and the gathering of an evidence base to further strengthen
      and refine the strategies of supplementation, fortification, breastfeeding, and
      food security. In responding to these challenges, multisectoral solutions and
      collaboration are critical in providing an evidence base to formulate policy. The
      role of the private sector, with the Nutrition Center of the Philippines used as
      an example, is that of a supportive and collaborative partner in good governance.
      Finally, the lessons learned from the past decades of implementing a national
      nutrition program, given changes in political and economic circumstances, are
      summarized.

PMID- 17209478
TI  - Nutritional status of adult Santal men in Keonjhar District, Orissa, India.
AB  - BACKGROUND: Although tribal people constitute a sizable proportion of India's
      population, there is little information on their anthropometric and nutrition
      status. OBJECTIVE: The present study was undertaken to study the anthropometric
      characteristics of adult Santal males. It also attempted to evaluate their
      nutritional status based on body-mass index (BMI) and mid-upper-arm circumference
      (MUAC). METHODS: A cross-sectional study was conducted of adult (aged > 18 years)
      male Santals, a tribal population of Keonjhar District, Orissa, India. A total of
      332 Santals from five villages (Gourshinga, Kashibera, Kumunia, Majhisahi, and
      Sonatangri) in the Anandapur Region of Keonjhar District were included in the
      study. These villages are located approximately 150 km from Bhubaneswar, the
      provincial capital of Orissa. Anthropometric measurements, including height,
      weight, and MUAC, were performed according to a standard protocol. Nutritional
      status was evaluated on the basis of internationally accepted cutoff points of
      BMI and MUAC. RESULTS: The mean height, weight, MUAC, and BMI of the men were
      162.5 cm, 51.7 kg, 23.7 cm, and 19.6 kg/m2, respectively. The prevalence of
      undernutrition (chronic energy deficiency [CED]) based on BMI was 26.2%; 3.3%,
      3.9%, and 19.0% had grades III, II, and I CED, respectively. According to MUAC
      cutoff points, the prevalence of undernutrition was 33.7%. CONCLUSIONS: The level
      of undernutrition among adult Santal males was high. Appropriate nutritional
      intervention programs should be implemented immediately.

PMID- 17209479
TI  - Celebrities in the ED: managers often face both ethical and operational
      challenges.
AB  - To prevent a celebrity's visit from disrupting your department, plan ahead to
      preserve their privacy and confidentiality--and recognize that they are not just
      like every other patient. Have secluded spaces available where they can wait to
      be seen while preserving their anonymity. Offer to have them registered under an
      alias, or sign them in as John or Jane Doe. Be aware that giving a wealthy VIP or
      large donor a positive experience can mean millions to your ED.

PMID- 17209480
TI  - Temblor drives ED staff, patients into outdoor tent.
AB  - Just because some disasters come without warning does not mean you shouldn't have
      an adequate response once it occurs. Be sure your disaster plan is in good order,
      and that you have a procedure in place for ensuring additional staff is
      available. If the is a threat to the structural integrity of your building,
      evacuate patients as quickly as possible. Ask maintenance and central supply to
      help with alternative facilities and portable equipment. Be prepared to function
      in less-than-ideal conditions for several days after the event.

PMID- 17209481
TI  - HICS is updated for consistency with NIMS.

PMID- 17209482
TI  - QI project slashes mislabeling rates.
AB  - You can achieve dramatic patient safety improvements by focusing on specific
      processes. One ED reduced major mislabeling events from 47% to 14%. Receive
      weekly updates on errors that occur so you can review them with staff while their
      memories are fresh. By looking at data from departmentwide processes, you can
      more readily identify common causes of errors. When discussing errors with staff,
      always take a nonaccusatory approach.

PMID- 17209483
TI  - Caffeine abuse may be missed in the ED.
AB  - ED managers should be aware of the tendency of young people to abuse caffeine and
      other nonprescription drugs. Experts say they end up in the ED more often than we
      think. Be sure to ask young patients with chest pain or heart palpitations
      whether they have taken any caffeine supplements. Be aware that most caffeine
      abusers also are abusing other pharmaceuticals such as dextramathorphan. Symptoms
      of caffeine abuse can include insomnia, tremors, sweating, nausea, vomiting,
      diarrhea, and neurological symptoms.

PMID- 17209484
TI  - 'Mystery shoppers' can uncover ED weaknesses.
AB  - One veteran "mystery shopper" has uncovered several common ED practices that can
      hurt patient satisfaction. You can learn from her observations to improve your
      ED's customer service: Be sure to let all of your patients know how long they
      might expect to wait before seeing a doctor. Wash your hands where the patient
      can see you, so they can be confident you are practicing good hygiene. Clearly
      explain all forms and discharge instructions to help ensure patient compliance.

PMID- 17209485
TI  - Final 2007 OPPS rule has some good news for EDs.

PMID- 17209486
TI  - AMI after low-dose IV epinephrine for anaphylaxis.

PMID- 17209487
TI  - The junkyard dogs find their teeth: addressing the crisis of admitted patients in
      Canadian emergency departments.

PMID- 17209488
TI  - Intravenous dexamethasone to prevent the recurrence of benign headache after
      discharge from the emergency department: a randomized, double-blind, placebo
      controlled clinical trial.
AB  - OBJECTIVE: To evaluate whether the addition of intravenous (i.v.) dexamethasone
      to standard emergency department (ED) benign headache therapy would reduce the
      incidence of headache recurrence at 48-72 hours. METHODS: This randomized, double
      blind, placebo-controlled clinical trial of adult patients presenting with the
      chief complaint of headache was conducted in the ED of 2 academic, urban Level 1
      hospitals. Headache evaluation and therapy were determined by the treating
      physician, and, before discharge, patients were administered either 10 mg of IV
      dexamethasone or placebo. The treatment groups had similar baseline
      characteristics, abortive therapy, IV fluids and degree of pain relief achieved
      before discharge. Patients were contacted 48-72 hours following discharge and
      asked whether their headache was "better," "worse" or "remained unchanged" when
      compared with their symptoms at discharge. Those whose headaches were "worse" or
      "unchanged," and those who reported a return of headache after being pain free at
      discharge were considered to be treatment failures and classified as having had a
      recurrence. The patient's headache at follow-up was further categorized as severe
      (i.e., provoking another physician visit or interfering with daily activity) or
      mild (i.e., requiring self-medication or no treatment). RESULTS: Fifty-seven
      patients met the inclusion criteria and 2 were lost to follow-up, leaving 55 for
      analysis. At follow-up, 9.7% (3/31) of those receiving dexamethasone had headache
      recurrence, versus 58.3% (14/24) of those receiving placebo (p < 0.001). Four
      dexamethasone recipients (12.9%) had severe headaches at follow-up compared with
      8 (33.3%) in the placebo group (p = 0.14). CONCLUSIONS: In this study, IV
      dexamethasone reduced headache recurrence at 48-72-hour follow-up. Given its
      excellent safety profile and likely benefit, IV dexamethasone should be
      considered for ED headache patients after standard evaluation and therapy.

PMID- 17209489
TI  - Diagnostic performance and potential clinical impact of advanced care paramedic
      interpretation of ST-segment elevation myocardial infarction in the field.
AB  - OBJECTIVES: Most studies of pre-hospital management of ST-elevation myocardial
      infarction (STEMI) have involved physicians accompanying the ambulance crew, or
      electrocardiogram (ECG) transmission to a physician at the base hospital. We
      sought to determine if Advanced Care Paramedics (ACPs) could accurately identify
      STEMI on the pre-hospital ECG and contribute to strategies that shorten time to
      reperfusion. METHODS: A STEMI tool was developed to: 1) measure the accuracy of
      the ACPs at diagnosing STEMI; and 2) determine the potential time saved if ACPs
      were to independently administer thrombolytic therapy. Using registry data, we
      subsequently estimated the time saved by initiating thrombolytic therapy in the
      field compared with in-hospital administration by a physician. RESULTS: Between
      August 2003 and July 2004, a correct diagnosis of STEMI on the pre-hospital ECG
      was confirmed in 63 patients. The performance of the ACPs in identifying STEMI on
      the ECG resulted in a sensitivity of 95% (95% confidence interval [CI] 86%-99%),
      a specificity of 96% (95% CI 94%-98%), a positive predictive value (PPV) of 82%
      (95% CI 71%-90%), and a negative predictive value (NPV) of 99% (95% CI 97%-100%).
      ACP performance for appropriately using thrombolytic therapy resulted in a
      sensitivity of 92% (95% CI 78%-98%), a specificity of 97% (95% CI 94%-98%), a PPV
      of 73% (95% CI 59%-85%) and an NPV of 99% (95% CI 97%-100%). We estimated that
      the median time saved by ACP administration of thrombolytic therapy would have
      been 44 minutes. CONCLUSIONS: ACPs can be trained to accurately interpret the pre
      hospital ECG for the diagnosis of STEMI. These results are important for the
      design of regional integrated programs aimed at reducing delays to reperfusion.

PMID- 17209490
TI  - Adequacy of antidote stocking in British Columbia hospitals: the 2005 Antidote
      Stocking Study.
AB  - BACKGROUND: Inadequate hospital stocking and the unavailability of essential
      antidotes is a worldwide problem with potentially disastrous repercussions for
      poisoned patients. Research indicates minimal progress has been made in the
      resolution of this issue in both urban and rural hospitals. In response to this
      issue the British Columbia Drug and Poison Information Centre developed
      provincial antidote stocking guidelines in 2003. We sought to determine the
      compliance with antidote stocking in BC hospitals and any factors associated with
      inadequate supply. METHODS: A 2-part survey, consisting of hospital demographics
      and antidote stocking information, was distributed in 2005 to all acute care
      hospital pharmacy directors in BC. The 32 antidotes examined (21 deemed
      essential) and the definitions of adequacy were based on the 2003 BC guidelines.
      Availability was reported as number of antidotes stocked per hospital and
      proportion of hospitals stocking each antidote. For secondary purposes, we
      assessed factors potentially associated with inadequate stocking. RESULTS:
      Surveys were completed for all 79 (100%) hospitals. A mean of 15.6+/-4.9
      antidotes were adequately stocked per hospital. Over 90% of hospitals had
      adequate stocks of N-acetylcysteine, activated charcoal, naloxone, calcium salts,
      flumazenil and vitamin K; 71%-90% had adequate dextrose 50% in water (D50W),
      ethyl alcohol or fomepizole, polyethylene glycol electrolyte solution, protamine
      sulfate, and cyanide antidotes; 51%-70% had adequate folic acid, glucagon,
      methylene blue, atropine, pralidoxime, leucovorin, pyridoxine, and deferoxamine;
      and <50% had adequate isoproterenol and digoxin immune Fab. Only 7 (8.9%)
      hospitals sufficiently stocked all 21 essential antidotes. Factors predicting
      poor stocking included small hospital size (p < 0.0001), isolation (p = 0.01) and
      rural location (p < 0.0001). CONCLUSION: Although antidote stocking has improved
      since the implementation of the 2003 guidelines, essential antidotes are absent
      in many BC hospitals. Future research should focus on determining the reasons for
      this situation and the effects of corrective interventions.

PMID- 17209491
TI  - Data collection on patients in emergency departments in Canada.
AB  - OBJECTIVE: Relatively little is known about the ability of Canadian emergency
      departments (EDs) and the federal, provincial and territorial governments to
      quantify ED activity. The objectives of this study were to determine the use of
      electronic patient data in Canadian EDs, the accessibility of provincial data on
      ED visits, and to identify the data elements and current methods of ED
      information system (EDIS) data collection nationally. METHODS: Surveys were
      conducted of the following 3 groups: 1) all ED directors of Canadian hospitals
      located in communities of >10,000 people, 2) all electronic EDIS vendors, and 3)
      representatives from the ministries of health from 13 provincial and territorial
      jurisdictions who had knowledge of ED data collection. RESULTS: Of the 243 ED
      directors contacted, 158 completed the survey (65% response rate) and 39% of
      those reported using an electronic EDIS. All 11 EDIS vendor representatives
      responded. Most of the vendors provide a similar package of basic EDIS options,
      with add-on features. All 13 provincial or territorial government representatives
      completed the survey. Nine (69%) provinces and territories collect ED data,
      however the source of this information varies. Five provinces and territories
      collect triage data, and 3 have a comprehensive, jurisdiction-wide, population
      based ED database. Thirty-nine percent of EDs in larger Canadian communities
      track patients using electronic methods. A variety of EDIS vendor options are
      available and used in Canada. CONCLUSION: The wide variation in methods and in
      data collected presents serious barriers to meaningful comparison of ED services
      across the country. It is little wonder that the majority of information
      regarding ED overcrowding in Canada is anecdotal, when the collection of this
      critical health information is so variable. There is an urgent need to place the
      collection of ED information on the provincial and national agenda and to ensure
      that the collection of this information consistent, comprehensive and mandatory.

PMID- 17209492
TI  - Pediatric appendicitis: pathophysiology and appropriate use of diagnostic
      imaging.
AB  - Evaluating children for appendicitis can be extremely difficult, and various
      strategies have been developed to improve the precision of preoperative
      diagnosis. Among these, ultrasound and computed tomography (CT) are now widely
      used but remain controversial. Although CT scanning is superior to ultrasound in
      terms of diagnostic accuracy for appendicitis, the large dose of ionizing
      radiation from CT and the risk of subsequent radiation-induced malignancy (RIM)
      are of particular concern in pediatric patients. This article reviews the
      literature on the pathophysiology, morbidity and mortality of appendicitis,
      summarizes the data regarding pediatric imaging in appendicitis, provides a
      practical approach to imaging for clinicians who evaluate pediatric patients, and
      makes recommendations for reducing the risk of RIM in pediatric patients.

PMID- 17209493
TI  - Myth: interpretation of a single ammonia level in patients with chronic liver
      disease can confirm or rule out hepatic encephalopathy.

PMID- 17209494
TI  - Where is the ET tube?

PMID- 17209495
TI  - Penetrating chest trauma secondary to a composite hockey stick injury.
AB  - Hockey is enjoyed by millions of people around the world and is a sport in which
      aggression is encouraged and injuries are common. Although body-checking is the
      most common cause of injury in hockey today, hockey sticks are associated with up
      to 14% of injuries. We report a case of chest trauma requiring surgical
      intervention secondary to the penetration of a composite hockey stick into a
      player's thoracic cavity.

PMID- 17209496
TI  - [Image of the month. Uterine malformation suggestive of adnexal mass].

PMID- 17209497
TI  - [How I treat...acne in adolescents: a strategic algorithm without antibiotic].
AB  - Acne is a multifaceted disorder. Its clinical presentation differs according to
      the age and gender of the subjects. Acne of the adolescent is a frequent
      disorder. Some topical and oral antibiotics have proven their efficacy. However,
      the risk of bacterial resistance may be a concern for the clinicians and their
      patients. Hence, a therapeutic strategy without antibiotics merits to be
      considered. Retinoids have a place of choice in this therapeutic strategy.
      Benzoyl peroxide and miconazole are also active and valuable agents in this
      therapeutic algorithm.

PMID- 17209498
TI  - [Relapse of testicular mixed germ cell tumor 15 years after initial treatment].
AB  - We report the case of a patient with a symptomatic retroperitoneal tumor. The
      patient had undergone, 15 years earlier, an orchiectomy and three cycles of
      chemotherapy for a testicular mixed germ cell tumor. Histology after radical
      surgical excision revealed a metastasis of mature teratoma. The 183 month
      interval between initial treatment and relapse is one of the longest ever
      reported.

PMID- 17209499
TI  - [Aortoaesophageal fistula caused by a thoracic aortic aneurysm].
AB  - Primary aorto-oesophageal fistula, secondary to an aneurysm of the thoracic
      aorta, are almost fatal. In the literature, only twenty six successfully operated
      cases have been reported. We report the case of a 78-year-old man with a thoracic
      aortic aneurysm eroded into the mid oesophagus. Prompt diagnosis of an aorto
      oesophageal fistula resulted from clinical history, CT-imaging and
      oesophagoscopy. The patient was successfully operated by exclusion of the
      thoracic aneurysm (insertion of a straight cryopreserved arterial allograft),
      oesophagectomy and cervical oesophagostomy and jejunostomy. The continuity of the
      digestive tube was later restored after preliminary aortic valve remplacement
      (stenosis of 0.8 cm2). This case report is the second in which a cryopreserved
      allograft was successfully implanted in the management of a primary aorto
      oesophageal fistula.

PMID- 17209500
TI  - [Aspirin for primary prevention of cardiovascular diseases in diabetic patients:
      focus on gender difference and insulin resistance].
AB  - Acetylsalicylic acid (aspirin) is widely used as antiplatelet therapy for the
      primary and secondary prevention of cardiovascular diseases. However, the effects
      appear to be different according to the studied population, with a reduction of
      coronary events in men and, rather, a diminution of strokes in women. Diabetes
      mellitus markedly increases the risk of cardiovascular diseases, with an
      especially elevated relative risk among women. We present a detailed analysis of
      the literature about the efficacy of aspirin in the primary prevention of
      cardiovascular complications in the diabetic population. Limited available data
      suggest a lower protection in the diabetic than in the non-diabetic population. A
      greater aspirin resistance has been suggested in diabetic patents, which might
      lead to the use of a higher daily dosage of aspirin in diabetic than in non
      diabetic patients. Whatsoever, aspirin remains the first antiplatelet agent in
      the diabetic population in all international guidelines of cardiovascular
      prevention.

PMID- 17209501
TI  - [Exacerbations in COPD: a burden to curtail].
AB  - Exacerbations of chronic obstructive pulmonary disease (COPD) play a very
      important role. Unfortunately they were neglected a long time in the therapeutic
      tests. However exacerbations influence the decline of the respiratory function
      over time, cause important deterioration of the quality of life of the patients,
      increase morbidity and mortality of COPD, and finally represent a burden for
      health care. Reducing the number of exacerbations could potentially slow down the
      progression of the disease. Thus the prevention of exacerbations should be the
      "corner stone" of the maintenance treatment of the COPD. In this review we
      propose to recall the importance of exacerbations in COPD and to present the
      treatment which have been shown to reduce exacerbation rate in COPD.

PMID- 17209502
TI  - [Carotid stenting revisited].
AB  - Recent publications about carotid-stenting are submitted to a critical analysis.
      The fact that an interventional approach in asymptomatic carotid lesions
      generates only marginal benefit being universally admitted, it is disturbing to
      see that modern series devoted to carotid artery stenting include a lot of
      asymptomatic patients and many symptomatic patients with a degree of stenosis
      well below the optimal range defined in NASCET (70 to 99%). Moreover, the degree
      of stenosis is often calculated from an inappropriate method that overestimates
      the degree of stenosis. Two objections have been made about an "hyper-selection"
      of the patients enrolled in the NASCET study and the production of ideal not
      realistic results, not attainable in community hospitals; both objections have
      been overruled. The rate of acute perioperative myocardial infarction is
      mentioned, both in NASCET and ECST, it is around 0.9% vs 7.5% in SAPPHIRE study.
      Moreover, carotid artery stenting with an embolic protection device has resulted
      in the production of infra-clinical cerebral micro-infarcts in 40% of the
      patients. Significantly, the independent study EVA-3S, devoted to symptomatic
      patients had to be stopped because of the high cerebral morbidity in the
      dilatation-stenting group. Carotid artery stenting of asymptomatic lesions is
      futile (and potentially harmful because of microinfarcts) while carotid artery
      stenting of symptomatic lesions generate emboli.

PMID- 17209503
TI  - [What's new at the maternal-foetal interface: role of the hCG/LH-hCG receptor
      couple during embryo implantation].
AB  - Implantation of the embryo into the maternal endometrium represents a unique
      biological process, combining an immunological (tolerance of an allograft) and
      biological (adhesion of two epitheliums) paradox. The success of implantation
      depends on a receptive endometrium, a functionally normal blastocyst and a
      synchronized cross-talk between embryonic and maternal tissues. Though sexual
      steroids control the process, a cascade of growth factors or cytokines are the
      prime paracrine mediators of the dialogue at the maternal-embryonic interface.
      HCG is one of the molecules most precociously produced by the embryo and is the
      most specific marker of its presence. HCG is a luteotropic factor which relays
      the inadequate support provided by the reduced rates of LH, but also influences
      the pregnancy on a paracrine mode by a local action on implantation process,
      probably by interacting with its receptor, the LH/hCG-R that we have evidenced on
      endometrial epithelium. We demonstrate that embryo actively participate into its
      implantation, tolerance and placentation.

PMID- 17209504
TI  - [Aspergillus pericarditis with cardiac tamponade and haemophagocytic syndrome: a
      non-classical case of immunodeficiency].
AB  - We report the case of a 31-year-old woman who died in a context of
      haemophagocytic syndrome with multiple opportunist infections:viral,
      mycobacterial and fungal. To our knowledge, this is the tenth case of invasive
      aspergillosis manifested by an aspergillus pericarditis with cardiac tamponade.
      Search for HIV infection, neoplasia, haematological malignancies was negative. In
      addition, the patient carried on a nonviral, non-ethylic cirrhosis, the etiology
      of which remained unknow. We will particularly develop the aspergillus
      pericarditis with cardiac tamponade and the haemophagocytic syndrome.

PMID- 17209505
TI  - [Linear dermatosis].
AB  - Some typical distributions of skin lesions represent a helpful sign for the
      differential diagnosis in dermatology. Indeed, some dermatoses, affecting the
      skin, nails or mucosae, display an annular or linear disposition. The linear
      pattern can be explained by several factors. The dermatosis can follow either a
      nerve traject, vascular or lymphatic vessels, or embryological lines. Exogenous
      factors, including traumatisms or automutilations, can also contribute to this
      particular distribution. In this review, the principal linear dermatoses are
      discussed together with their pathogenesis.

PMID- 17209506
TI  - [Profile of basal cell carcinomas of the scalp after radiotherapy for tinea
      capitis (about 63 cases)].
AB  - The induction of basal cell carcinoma (BCC) of the scalp by X-ray therapy for
      tinea capitis is well known. The aim of the study was to specify the
      epidemiological, clinical and histological characteristics of this disease. In a
      retrospective study, we collected data from the files of 63 patients, with a
      history of radiotherapy for tinea capitis, followed between January 1995 and
      December 2004. Fifty one men and 12 women with a total of 108 BCC of the scalp
      are reported (1.76 lesion per patient and 1.13 cm on average of diameter). The
      mean age at the occurrence of the BCC was 45.5 years. Thirty seven percent of BCC
      occurred on the occipital area; 28.7% were in the parietal site. The most
      frequent clinical aspect was the nodular BCC (51%) and the cicatricial BCC (35%).
      Histological study showed a nodular aspect in 74 % and pigmentation in 62% of
      cases. It is concluded that BCC of the scalp following X-ray therapy for tinea
      capitis have some clinical and histological particularities. It represents the
      most frequent tumour developing on irradiated scalp.

PMID- 17209507
TI  - [DREAM study: prevention of type 2 diabetes with ramipril and/or rosiglitazone in
      persons with dysglycaemia but no cardiovascular desease].
AB  - DREAM ("Diabetes Reduction Assessment with ramipril and rosiglitazone
      Medication") is a double-blind randomised placebo-controlled clinical trial with
      a 2-by-2 factorial design aiming to study the effects of an ACE inhibitor
      (ramipril 15 mg/day) and/or a thiazolidinedione (rosiglitazone 8 mg/day) on the
      development of diabetes or death (primary outcome) and on the regression to
      normoglycaemia (secondary outcome) in 5269 adults aged 30 years or more with
      impaired fasting glucose and/or impaired glucose tolerance, and no previous
      cardiovascular disease. There was no statistical evidence of an interaction
      between the ramipril and the rosiglitazone arms. After a mean follow up of 3
      years, the use of ramipril does not significantly reduce the incidence of
      diabetes or death but does significantly increase regression to normoglycaemia.
      In contrast, the treatment with rosiglitazone reduces by almost 60% the incidence
      of type 2 diabetes and increases the likelihood (+70%) of regression to
      normoglycaemia. Whether it is a true prevention effect or simply a treatment
      effect remains to be determined when participants will be retested after a
      washout period. Cardiovascular event rates were rather low and much the same in
      all treatment groups, except a higher rate of heart failure in the rosiglitazone
      group. These results suggest that the routine inhibition of the renin-angiotensin
      system for the express purpose of preventing diabetes is not indicated in
      individuals not at high risk for cardiovascular disease and appear to confirm the
      promises of the glitazone use in the very early stage of the natural history of
      type 2 diabetes.

PMID- 17209508
TI  - Establishment of an early warning system against bluetongue virus in Switzerland.
AB  - Bluetongue (BT) is a vector-borne animal disease of economical importance due to
      the international trade restrictions likely to be put into place in a country
      once the infection is discovered. The presence of BT and its vectors in countries
      adjacent to Switzerland stresses the need of implementing a surveillance system
      and to raise disease awareness among potential stakeholders. A national survey in
      Switzerland 2003 indicated freedom of Bluetongue virus (BTV), although a single
      individual of the main BT vector Culicoides imicola was caught in the canton of
      Ticino. The survey also demonstrated that potential BT vectors, C. obsoletus and
      C. pulicaris are locally abundant in Switzerland. Therefore, a new surveillance
      method based on sentinel herds in high risk areas was implemented in 2004 for the
      early detection of both an incursion of BT vectors into Switzerland, and
      potential virus circulation among cattle.

PMID- 17209509
TI  - Histomorphological and immunohistochemical findings in testes, bulbourethral
      glands and brain of immunologically castrated male piglets.
AB  - The aim of this study was the histological and immunohistochemical evaluation and
      comparison of testicular, bulbourethral and brain tissue in immunized and intact
      control boars. Fourteen male piglets, aged between 10 and 16 weeks, were
      vaccinated twice subcutaneously 4 to 5 weeks apart with Improvac, an anti-GnRH
      vaccine. The pigs were sacrificed 1 to 16 weeks following the second injection.
      Testicular weight was recorded and various tissue samples were collected and
      fixed in formalin and Bouin's fixative for histological examination. In addition,
      2 boars were immunized five times and slaughtered 60 weeks after the last
      injection. Histological and immunohistological studies performed on testes and
      epididymes showed clear signs of atrophy in the immunized animals and a
      significant reduction in paired testes weight was seen in treated boars.
      Microscopically, the mean diameter of the seminiferous tubules was markedly
      reduced. Spermatogonia as well as few spermatocytes were visible between the
      Sertoli cells and Leydig cells were atrophic. None or only few spermatozoa were
      detected in the epididymis. The bulbourethral glands of immunocastrated pigs were
      smaller than in control pigs and showed histological evidence of atrophy.
      Immunohistological detection of LH and FSH in the pituitary gland of treated and
      control boars showed no quantifiable difference in the amount of these two
      gonadotropins and no lesions were visible in the hypothalamus and the pituitary
      gland. From our findings it can be concluded that the anti-GnRH vaccine Improvac
      induces severe atrophy of testes and bulbourethral glands in immunized pigs. This
      effect appears to be reversible, depending on the immune response of each animal
      and the time elapsed after the last booster injection.

PMID- 17209510
TI  - [Cerebrospinal nematodosis in sheep in Switzerland].
AB  - In December 2005 three sheep, originating from Canton Tessin, were presented with
      cerebrospinal nematodosis. The animals had a history of progressive pelvic limb
      ataxia and recumbency. The most important clinical findings were an abnormal gait
      (wide stance, pelvic limb paresis) and decreased sensitivity of the pelvic limbs.
      The general condition was slightly or moderately disturbed, appetite was normal.
      Examination of the cerebrospinal fluid revealed mononuclear cells and
      eosinophils, suggesting a helminthic infection of the central nervous system.
      Postmortem findings confirmed the clinical diagnosis in one animal as parts of a
      nematode were found in the thoracic spinal cord. Even though the nematode could
      not be identified, infection with Elaphostrongylus cervi seems very likely, as
      the sheep are in close contact with deer on the pastures and the parasite is
      known to infect goats in Switzerland. This is the first description of
      cerebrospinal nematodosis in sheep in Switzerland.

PMID- 17209511
TI  - Unilateral evisceration of an eye following cornea and lens perforation in a
      sulfur-crested cockatoo (Cacatua galerita).
AB  - A 24-year old male sulfur-crested Cockatoo (Cacatua galerita) was presented with
      a subacute perforation of the cornea without involvement of the lens. The bird
      was treated conservatively and the eye remained quiescent up to a second
      traumatic corneal perforation associated with a lens capsule rupture 15 months
      later. Due to the second perforating trauma of an already blind eye involving the
      lens, evisceration of the eye was performed. Two months after surgery the
      cosmetic result was excellent. Treatment options for perforating ocular traumas
      in captive birds are discussed in detail.

PMID- 17209512
TI  - Antioxidant and prooxidant activities of B group vitamins in lipid peroxidation.
AB  - The antioxidant and prooxidant activities of six B group vitamins against
      hydroperoxide generation in linoleic acid peroxidation were analyzed by the
      aluminum chrolide method. The B group vitamins were divided into three types by
      their antioxidant and prooxidant properties. The first type, including B1, B2
      vitamin, nicotinic acid and folic acid, showed prooxidant activities in the early
      phase (1 week) of the linoleic acid peroxidation at concentrations of 2.5 microM
      2.5 mM, but caused relatively strong antioxidant activities in the later phase
      reaction (3 weeks) at the same concentrations. The second type, such as B12
      vitamin, did not cause significant effects in the early phases (1-2 weeks) of
      linoleic acid peroxidation, but exhibited significant antioxidant activities in
      the later phase reactions (3 weeks). The third type, such as B6 vitamin,
      exhibited significant antioxidant activity in the early phase reaction and caused
      strong antioxidant effects in the later phase reaction (3 weeks). Generally, the
      antioxidant activities of B group vitamins in the later phases of lipid
      peroxidation was much stronger than those in the earlier phases. These
      experimental results suggest a possibility that B group vitamins have both
      antioxidant and prooxidant effects on lipid peroxidation under different
      experimental conditions.

PMID- 17209513
TI  - No potential role of genetic polymorphisms for IL-4, IL-13 and IL-4 receptor in
      respiratory allergy: a study in adults working at social welfare facilities in
      Korea.
AB  - Indoor air in public facilities contains various pollutants jeopardizing the
      health of employees or occupants in the facilities. We evaluated the respiratory
      allergy-related immune status of employees, and investigated a role of genetic
      predisposition on respiratory allergy occurrence in the employees. Among 23
      workers from 5 facilities, 48% were positive for aeroallergens. House dust mite
      was the major allergen demonstrating positive skin reactions. The level of plasma
      IgE, an immunologic marker for allergic hypersensitivity induction, was
      upregulated in the allergy positive employees. The percentage of eosinophils in
      peripheral blood was also higher in the allergy positive employees than in the
      employees with negative skin test results. We also evaluated genetic
      polymorphisms on interleukin-4 (IL-4) receptor alpha chain (Gln576Arg and
      Ile50Val), IL-4 (C589T) and interleukin-13 (Arg130Gln), which has been implicated
      in asthma induction in children. However, no higher frequencies of these genetic
      variations were found in the adults with positive skin test results for
      aeroallergens. This study implies that workers in social welfare facilities may
      have a substantial risk of suffering from respiratory allergy associated with
      exposure to aeroallergens, but genetic variations in the IL-4 receptor alpha
      chain, IL-4 and IL-13 may not be critical in adult workers for the development of
      respiratory allergic diseases.

PMID- 17209514
TI  - Targeted intra-arterial carboplatin chemoradiotherapy and tegafur/uracil for oral
      and oropharyngeal cancer.
AB  - The aim of this study was to evaluate the usefulness of targeted intra-arterial
      carboplatin chemoradiotherapy in allowing less invasive surgery for patients with
      oral and oropharyngeal squamous cell carcinoma. Twenty patients with previously
      untreated squamous cell carcinoma of the oral cavity and oropharynx (T4; 8, T2;
      12 patients) were treated with targeted transfemoral intra-arterial carboplatin
      infusion with concurrent hyperfractionated radiotherapy and the administration of
      tegafur/uracil (UFT). Of 20 patients, 15 underwent surgery after completion of
      one course of targeted chemoradiotherapy, and five were given another course or
      radiotherapy only. Eighteen (90%) of 20 patients had a clinically complete
      response at the primary site and two (10%) had a partial response. Of the 15
      patients who underwent tumor resection, 11 (73%) showed histopathological
      disappearance of cancer cells at the primary site. Sixteen (80 %) of 20 tumors
      were controlled at the primary site within a mean follow-up of 30 months. Adverse
      effects were relatively mild. Targeted intra-arterial chemoradiotherapy caused a
      down-staging of tumors and facilitated the use of less invasive surgery in
      patients with squamous cell carcinoma of the oral cavity and oropharynx as a
      result of its favorable anti-tumor effect.

PMID- 17209515
TI  - [Measurement of gene expression of CYP mRNA in liver of rats exposed to toluene
      and 1-butanol vapors].
AB  - A reduction of the biological half life of toluene in blood in the simultaneous
      exposure to toluene and alcohol vapors has been reported. To clarify the cause of
      this reduction, gene expression of CYP mRNA in liver of rats exposed to bi
      component organic vapors was investigated. Wistar male rats were repeatedly
      exposed to 500 ppm of toluene and 300 ppm of 1-butanol vapors individually and
      simultaneously by inhalation 6 hours a day, five days a week for 4 weeks. After
      the exposure, the rats were sacrificed and the livers were collected and
      homogenized. RNA was extracted from the livers, and gene expression of CYP mRNA
      was observed by reverse transcription-polymerase chain reaction (RT-PCR). The
      gene expression of CYP3A2 in the simultaneous exposure group was significantly
      higher than that in the toluene exposure group. However, there was no significant
      difference in that of CYP1A2, CYP2B1, CYP2C11, CYP2E1 and CYP4A1.

PMID- 17209516
TI  - [Survival of Gram-positive spore-forming bacteria including Bacillus cereus after
      hand washing using alcohol-based handrub].
AB  - Hand washing is the most fundamental method for preventing infection. Currently,
      hand washing with an alcohol-based handrub is the international gold standard
      method. However, in our study we found many samples of ineffective hand washing
      using an alcohol-based handrub. The rates of ineffective samples were 10.4%
      (5/48) in 2004 and 34.3% (12/35) in 2005. We examined the morphology by Gram
      staining and biochemical properties of the bacteria which remained after hand
      washing in 2005. Their colonies were divided into 3 groups (round colonies,
      irregular-shaped and diffusive colonies). The round colonies were considered
      Staphylococcus spp., and the irregular-shaped colonies or diffusive colonies were
      considered Gram-positive spore-forming bacteria. In the 12 ineffective hand
      washing samples (more than the same number of bacteria colonies as before hand
      washing, or > or = 300), there were 3 samples considered to be the result of the
      survival of Staphylococcus spp., and 9 samples considered to be the result of the
      survival of Gram-positive spore-forming bacteria including Bacillus cereus. Based
      on these results, we should take careful measures, such as wearing sterile gloves
      if necessary. We should never be overconfident regarding the effect of hand
      washing.

PMID- 17209517
TI  - [Effect of oral health care program on the oral function of the elderly].
AB  - In order to prepare a new prevention program under the long term care insurance
      from the fiscal year 2006, we have organized an oral health care program for the
      elderly in a town of Kagoshima prefecture. We conducted a series of oral health
      education, i.e., instruction on brushing and flossing, and oral function
      exercises. Before and after the three months program, we evaluated the
      unstimulated and stimulated salivary flow rate, the counts of S. mutans, the
      counts of repetitive saliva swallowing test (RSST), bilateral bite force and the
      number of permanent teeth and artificial teeth. According to the results, a
      statistically significant improvement was observed in RSST and the unstimulated
      and stimulated salivary flow rate, but not in the S. mutans level and bite force.
      The present research suggests the effectiveness of the oral health care program
      for the aged. A larger sized and longer period intervention will be necessary in
      order to validate our findings.

PMID- 17209518
TI  - [Construction of occupational zoonoses control system at a zoo].
AB  - More than 200 diseases are known to be transmitable from animals to humans. These
      zoonotic infections (zoonoses) are considered as a major occupational health risk
      among zoo workers, including veterinarians and animal handlers. In order to
      prevent possible pathogen transmission, precaution measures for workers, visitors
      and animals are important, as well as institutional hygiene. Construction of a
      zoonoses control system at a zoo is presented in this report. There are two main
      components of this system: 1. routine disease prevention activity, 2. action
      planning for crisis. Workers, an operating officer, an occupational physician and
      a veterinarian from the zoo cooperated with infection control professionals from
      the local community.

PMID- 17209519
TI  - [The preparatory education of electronic patient record for nursing students
      before practical nursing training].
AB  - Preparatory education has been provided for both nursing students and teachers to
      understand the electronic patient record (EPR) since 2004 when EPR was introduced
      to the hospitals where students are allocated to undertake their work experience.
      First, the training and management board contacted our medical information
      department for an appointment and sent us a working group. They taught the
      nursing training staff how to use EPR and how to assign students to the proper
      patient record in the EPR system. Second, as preparatory education for the
      students, they explained the procedure for the use of EPR and the protection of
      personal information. Students practiced with training in the EPR system,
      focusing on the functions which are used frequently in practical tasks. As a
      result of this preparatory education, students understood the protection of
      personal information very well, although their understanding of the operation and
      management of the equipment was relatively poor and adversely affected their
      practice. We need to review our education contents more often. We also need to
      examine the present state of understanding of EPR and the problems of teaching in
      practical nursing training.

PMID- 17209521
TI  - Therapeutic potential of Aurora kinase inhibitors in cancer.
AB  - Aurora kinases (AKs) represent a family of serine/threonine protein kinases that
      regulate mitotic processes during cell division. They are primarily involved in
      regulating the multiple steps of mitosis, including centrosome duplication,
      formation of bipolar mitotic spindle, chromosome alignment on the mitotic
      spindle, establishment and maintenance of the spindle checkpoint and cytokinesis.
      As AKs are key regulators of mitosis, several studies have indicated that they
      have a strong association with cancer and are overexpressed in numerous cancerous
      cell lines as well as human malignancies. Thus, AKs represent a promising
      therapeutic target for anticancer drug development. In this review, the role of
      AKs in cancer, and the current status and therapeutic potential of AK inhibitors
      is discussed.

PMID- 17209522
TI  - New strategies to improve the efficacy of colorectal cancer vaccines: from bench
      to bedside.
AB  - By exploiting a naturally occurring defense system, anticancer vaccination
      embodies an ideal non-toxic treatment capable of evoking tumor-specific immune
      responses that can ultimately recognize and kill colorectal cancer (CRC) cells.
      Despite the enormous theoretical potential of active specific immunotherapy, no
      vaccination regimen has achieved sufficient therapeutic efficacy necessary for
      clinical implementation. Nevertheless, several immunological advances have opened
      new avenues of research to decipher the biological code governing tumor immune
      responsiveness, and this is leading to the design of potentially more effective
      immunotherapeutic protocols. This review briefly summarizes the principles behind
      anti-CRC vaccination and describes the most promising immunological strategies
      that have been developed, which are expected to renew interest in this
      molecularly targeted anticancer approach.

PMID- 17209523
TI  - Targeted therapy for colorectal cancer.
AB  - There has been a revolution in the treatment of colorectal cancer over the last
      decade. Part of this revolution has been the discovery of agents that target
      particular aspects of cancer, namely vascular endothelial growth factor and
      epidermal growth factor receptor. Novel targeted agents have been evaluated in
      clinical trials and have demonstrated significant anticancer activity.
      Furthermore, a number of these compounds have been approved for clinical use.
      Data supporting the use of targeted agents in the treatment of colorectal cancer
      are reviewed, and the "future for potential novel agents and pathways are
      discussed.

PMID- 17209524
TI  - Inhibitors of hypoxia-inducible factor-1 signaling.
AB  - Hypoxia is a universal feature of solid tumors that arises as the tumor mass
      outgrows stromal vascular supply. Hypoxia-inducible factor (HIF)-1, a
      transcription factor upregulated in hypoxia, orchestrates a range of adaptive
      responses that allow tumor cells to survive oxygen deprivation. Important
      information regarding the role of HIF-1 in tumor biology was gained from tumor
      biopsy studies in which HIF-1 expression was strongly associated with poor
      patient prognosis, and from animal studies in which genetic ablation of HIF-1
      signaling retarded tumor growth. These findings motivated an intensive search for
      small-molecule inhibitors of the HIF-1 pathway. This review describes the
      progress toward the identification of specific inhibitors of HIF-1, and discuss
      the first examples of HIF-1-targeted therapeutics to enter clinical development.

PMID- 17209525
TI  - Small-molecule inhibitors of Bcl-2.
AB  - Cancer cells with elevated levels of Bcl-2 and the related anti-apoptotic
      proteins Bcl-x(L), Mcl-1 and Bcl-W are broadly resistant to standard anticancer
      drugs and other therapeutic modalities. Antisense oligodeoxynucleotides and, more
      recently, small-molecule ligands for Bcl-2 and Bcl-x(L), sensitize cancer cells
      to cytotoxic therapies. In some cases, Bcl-2-targeted therapies can function as
      single therapeutic agents to kill tumor cells, suggesting that Bcl-2 has an
      important role in the critical functions of cancer cells. The molecular
      mechanisms of Bcl-2 are not completely understood, therefore, the validation of
      cytotoxic mechanisms related to Bcl-2 as well as the identification of surrogate
      markers for Bcl-2 function are significant obstacles for drug development.
      Despite these problems, two Bcl-2 small-molecule inhibitors are currently
      undergoing phase I/II clinical trials and several other compounds are in
      preclinical development. Ongoing studies with these investigational drugs should
      provide new insights into optimal strategies to disrupt Bcl-2 survival functions
      to selectively kill cancer cells.

PMID- 17209526
TI  - Non-steroidal anti-estrogens in the treatment of breast cancer.
AB  - The non-steroidal selective estrogen receptor modulator (SERM) tamoxifen has been
      used as standard first-line therapy for postmenopausal breast cancer since the
      1970s, during which time over 400,000 lives have been saved. Nevertheless, much
      attention has been paid to the side effect profile of tamoxifen, particularly in
      terms of cardiovascular and endometrial abnormalities. Third generation non
      steroidal aromatase inhibitors, such as anastrozole and letrozole, have been
      approved as an alternative, although it is still too early to judge what long
      term adverse effects might be associated with prolonged restriction of the supply
      of estrogen. Novel SERMs have demonstrated improved characteristics over
      tamoxifen, reducing or eliminating certain adverse events while retaining breast
      tumor-reducing efficacy. Thus, these agents could provide a direct substitute for
      tamoxifen. In addition, other estrogen receptor (ER) subtype-selective modulators
      are under investigation, and the importance of ERbeta as a positive prognostic
      indicator may open up further therapeutic opportunities. Resistance to hormonal
      therapies is still a major problem and identifiying the onset of the development
      of resistance, together with earlier intervention with inhibitors of growth
      factor driven cell survival pathways, in combination or sequentially, requires
      more intense study.

PMID- 17209527
TI  - Drug evaluation: tesetaxel--an oral semisynthetic taxane derivative.
AB  - Daiichi Sankyo Co Ltd (formerly Daiichi Seiyaku Co Ltd) was developing the oral
      semisynthetic taxane derivative tesetaxel for the potential treatment of cancer,
      including colorectal and gastric cancer. However, despite early signs of promise,
      in November 2006 tesetaxel was removed from Daiichi's development pipeline for
      failure to show clear benefit over existing, currently marketed agents for cancer
      chemotherapy.

PMID- 17209528
TI  - Drug evaluation: Lymphoseek - Neoprobe's sentinel lymph node imaging agent for
      use in cancer patients.
AB  - Neoprobe, under license from the University of California San Diego Cancer
      Center, is developing 99mTc-DTPA-mannosyl-dextran (Lymphoseek) as a potential
      agent for imaging lymph nodes in patients undergoing treatment for breast cancer
      and melanoma. Phase II trials of Lymphoseek were initiated in mid 2006.

PMID- 17209529
TI  - Drug evaluation: the thioredoxin inhibitor PX-12 in the treatment of cancer.
AB  - Biomira Inc, following its acquisition of ProlX Pharmaceutical Corp, is
      developing PX-12, an inhibitor of thioredoxin, for the potential treatment of
      cancer. PX-12 has completed phase I clinical trials.

PMID- 17209530
TI  - 'Lost data' revisited.

PMID- 17209531
TI  - Tooth development: 1. Generating teeth in the embryo.
AB  - Teeth are organs that develop in the embryo via a series of interactions between
      oral epithelium and neural crest-derived ectomesenchyme of the early jaws. These
      interactions are initiated by the regional production of signalling molecules in
      the oral epithelium and the transfer of information to the underlying mesenchyme
      via homeobox gene transcription. This article describes how these interactions
      are co-ordinated in the embryo during development of the dentition and provides a
      theoretical basis for the second article in this series; understanding how
      biologists are attempting to generate teeth artificially in the laboratory.

PMID- 17209532
TI  - Modern restorative management of patients with congenitally missing teeth: 2.
      Orthodontic and restorative considerations.
AB  - Managing edentulous spaces in patients with congenitally missing teeth demands
      careful planning and, often, a multidisciplinary approach. Orthodontic tooth
      movement can be considered to close spaces as well as improve the distribution of
      available teeth. In this second paper, the advantages of a collaborative approach
      are discussed.

PMID- 17209533
TI  - Patient-centred measures in dental practice: 1. An overview.
AB  - This paper explores the way that patient participation has increased in dentistry
      in recent years and introduces the two concepts of 'quality of life' and 'patient
      satisfaction' and examines their relevance to everyday clinical dental practice.

PMID- 17209534
TI  - Aerosols and splatter in dentistry--a neglected menace?
AB  - Two main types of particulate matter may be produced during routine dental
      procedures, namely aerosols and splatter. The principal difference between them
      is the size of the particles from which they are made. The behaviour of such
      particles in air and their possible health risks are complex. However, the use of
      high volume evacuation, pre-procedural mouthrinses and rubber dam are the most
      effective methods of reducing the unwanted risk of exposure.

PMID- 17209535
TI  - Double permanent incisor teeth: management of three cases.
AB  - Double teeth in the permanent dentition have a reported incidence of 0.1% for
      Caucasian groups. Common associated problems include adverse aesthetics, caries,
      periodontal disease, and malocclusions. Management can be challenging, often
      requiring a multidisciplinary approach. Three cases are presented illustrating
      the variety of treatments available.

PMID- 17209536
TI  - Amelogenesis imperfecta--clinical presentation and management: a case report.
AB  - Amelogenesis imperfecta (AI) is an inherited disorder which results in enamel
      defects. The presentation of AI can vary depending on the type and severity of
      AI. The management of this condition is important for the patient, both
      functionally and aesthetically. This report describes the management of a young
      man who was referred to Birmingham Dental Hospital with AI. The patient's primary
      complaint was the appearance of his front teeth and the sensitivity he was
      experiencing from his worn molar teeth.

PMID- 17209537
TI  - Haematological considerations in patients with cyanotic congenital heart disease:
      a review.
AB  - In patients with cyanotic congenital heart disease (CCHD), the need for prior
      antibiotic prophylaxis for infective endocarditis is well known to dentists, but
      not many dentists are aware of the associated haemorrhagic tendencies in such
      patients. Haemostatic abnormalities associated with CCHD are an important aspect
      that is often overlooked by both physicians and dentists. We briefly review the
      literature to highlight the importance of more elaborate haematological
      evaluation in patients with CCHD, prior to any oral surgical procedures.

PMID- 17209538
TI  - Peripheral ameloblastoma: a case report.
AB  - Peripheral ameloblastoma is an uncommon pathological variant of the more usual
      intraosseous central ameloblastoma. It most typically presents as a localized
      soft tissue mass occurring in the tooth-bearing areas of the jaws and is often
      provisionally diagnosed as an epulis. In this paper, a 43-year-old male presented
      with a three-year history of a painful, slowly enlarging gingival swelling. There
      was no evidence of bony involvement on radiographs but it was revealed
      histologically to be a peripheral ameloblastoma. Treatment was by wide local
      excision, including a bony margin, and primary closure. Long-term follow-up is
      imperative owing to possible recurrence and malignant potential.

PMID- 17209539
TI  - Good night, squashbite: a 'how to' paper on better wax occlusal records.
AB  - During the technical stages of dental treatment, a dental technician may only be
      able to unite a set of dental casts in a 'best-guess' relationship, unless they
      are either able to examine the patient themselves, or are given further
      information about the occlusal position chosen during the clinical procedure. The
      most common method for this is to use some form of occlusal record, which can be
      created from a variety of techniques and materials, such as either one of the
      dental waxes or one of the more recently introduced syringable materials. This
      paper describes a better technique for using dental wax to make occlusal records.
      The 'squashbite' technique has no place in clinical dentistry for those
      attempting to obtain accurate results.

PMID- 17209540
TI  - Oral mucosal ulceration due to ferrous sulphate tablets: report of a case.
AB  - Recurrent oral ulceration due to underlying iron-deficiency anaemia is already
      recognized. However, this case report describes a 78-year-old lady who developed
      severe ulceration of the tongue and floor of the mouth as a result of the
      treatment of iron-deficiency anaemia with ferrous sulphate tablets. Withdrawal of
      the ferrous sulphate tablets and replacement with ferrous fumarate syrup led to
      resolution of the lesion.

PMID- 17209541
TI  - Physical signs for the general dental practitioner.

PMID- 17209542
TI  - Aspects of human disease.

PMID- 17209543
TI  - Solution NMR of large molecules and assemblies.
AB  - Solution NMR spectroscopy represents a powerful tool for examining the structure
      and function of biological macromolecules. The advent of multidimensional (2D-4D)
      NMR, together with the widespread use of uniform isotopic labeling of proteins
      and RNA with the NMR-active isotopes, 15N and 13C, opened the door to detailed
      analyses of macromolecular structure, dynamics, and interactions of smaller
      macromolecules (< approximately 25 kDa). Over the past 10 years, advances in NMR
      and isotope labeling methods have expanded the range of NMR-tractable targets by
      at least an order of magnitude. Here we briefly describe the methodological
      advances that allow NMR spectroscopy of large macromolecules and their complexes
      and provide a perspective on the wide range of applications of NMR to biochemical
      problems.

PMID- 17209544
TI  - High-risk HPV E6 oncoproteins assemble into large oligomers that allow
      localization of endogenous species in prototypic HPV-transformed cell lines.
AB  - The E6 oncoproteins of high-risk HPV types 16 and 18 are involved in the
      development of cervical cancer. Besides its determinant role in carcinogenic
      progression, HPV E6 oncoprotein has also been instrumental in elucidating
      fundamental aspects of p53 function and its ubiquitin-proteasome degradation,
      with counterpart activities in various DNA tumor viruses. Establishing the
      conformational state and cellular distribution unequivocally for the endogenous
      protein in HPV-transformed cell lines derived from carcinomas is essential for
      understanding the underlying mechanism. Recombinant E6 from high-risk strains 16
      and 18 folds into soluble oligomers of approximately 1.2 MDa, which are
      thermostable and display cooperative loss of tertiary and secondary structure
      upon chemical denaturation. Antibodies raised against these assemblies locate E6
      evenly distributed in the cells. By depleting the polyclonal serum by
      immunoblocking with monomeric E6, the nuclei of Hela and CaSki cells become
      completely devoid of label, indicating that monomeric species are mainly
      localized in the nucleus and that both monomers and oligomers share epitopes. The
      monomeric species promote degradation of p53 by the proteasome, which correlates
      with the nuclear localization we describe. In contrast, the oligomeric E6 does
      not promote p53 degradation, in agreement with its cytoplasmic localization
      inferred from the immunoneutralization experiments. Our results indicate that the
      cytoplasmic species contain conformational epitopes that may arise from yet
      undefined homo or hetero-oligomers, but its localization otherwise agrees with
      that of the other group of major E6 targets, those involving PDZ binding domains,
      which requires further investigation.

PMID- 17209545
TI  - Functional interrogation of the kinome using nucleotide acyl phosphates.
AB  - The central role of protein kinases in signal transduction pathways has generated
      intense interest in targeting these enzymes for a wide range of therapeutic
      indications. Here we report a method for identifying and quantifying protein
      kinases in any biological sample or tissue from any species. The procedure relies
      on acyl phosphate-containing nucleotides, prepared from a biotin derivative and
      ATP or ADP. The acyl phosphate probes react selectively and covalently at the ATP
      binding sites of at least 75% of the known human protein kinases. Biotinylated
      peptide fragments from labeled proteomes are captured and then sequenced and
      identified using a mass spectrometry-based analysis platform to determine the
      kinases present and their relative levels. Further, direct competition between
      the probes and inhibitors can be assessed to determine inhibitor potency and
      selectivity against native protein kinases, as well as hundreds of other ATPases.
      The ability to broadly profile kinase activities in native proteomes offers an
      exciting prospect for both target discovery and inhibitor selectivity profiling.

PMID- 17209546
TI  - Characterization of the aminocarboxycyclopropane-forming enzyme CmaC.
AB  - The biosynthesis of the coronamic acid fragment of the pseudomonal phytotoxin
      coronatine involves construction of the cyclopropane ring from a gamma-chloro-L
      allo-Ile intermediate while covalently tethered as a phosphopantetheinyl
      thioester to the carrier protein CmaD. The cyclopropane-forming catalyst is CmaC,
      catalyzing an intramolecular displacement of the gamma-Cl group by the alpha
      carbon. CmaC can be isolated as a Zn2+ protein with about 10-fold higher activity
      over the apo form. CmaC will not cyclize free gamma-chloro amino acids or their S
      N-acetylcysteamine (NAC) thioester derivatives but will recognize some other
      carrier protein scaffolds. Turnover numbers of 5 min-1 are observed for Zn-CmaC,
      acting on gamma-chloro-L-aminobutyryl-S-CmaD, generating 1-aminocyclopropane-1
      carbonyl (ACC)-S-CmaD. Products were detected either while still tethered to the
      phosphopantetheinyl prosthetic arm by mass spectrometry or after thioesterase
      mediated release and derivatization of the free amino acid. In D2O, CmaC
      catalyzed exchange of one deuterium into the aminobutyryl moiety of the gamma-Cl
      aminoacyl-S-CmaD, whereas the product ACC-S-CmaD lacked the deuterium, consistent
      with a competition for a gamma-Cl-aminobutyryl alpha-carbanion between
      reprotonation and cyclization. CmaC-mediated cyclization yielded solely ACC,
      resulting from C-C bond formation and no azetidine carboxylate from an alternate
      N-C cyclization. CmaC could cyclize gamma,gamma-dichloroaminobutyryl to the Cl
      ACC product but did not cyclize delta- or epsilon-chloroaminoacyl-S-CmaD
      substrates.

PMID- 17209547
TI  - Characterization of human UDP-glucose dehydrogenase reveals critical catalytic
      roles for lysine 220 and aspartate 280.
AB  - Human UDP-glucose dehydrogenase (UGDH) is a homohexameric enzyme that catalyzes
      two successive oxidations of UDP-glucose to yield UDP-glucuronic acid, an
      essential precursor for matrix polysaccharide and proteoglycan synthesis. We
      previously used crystal coordinates for Streptococcus pyogenes UGDH to generate a
      model of the human enzyme active site. In the studies reported here, we have used
      this model to identify three putative active site residues: lysine 220, aspartate
      280, and lysine 339. Each residue was site-specifically mutagenized to evaluate
      its importance for catalytic activity and maintenance of hexameric quaternary
      structure. Alteration of lysine 220 to alanine, histidine, or arginine
      significantly impaired enzyme function. Assaying activity over longer time
      courses revealed a plateau after reduction of a single equivalent of NAD+ in the
      alanine and histidine mutants, whereas turnover continued in the arginine mutant.
      Thus, one role of this lysine may be to stabilize anionic transition states
      during substrate conversion. Mutation of aspartate 280 to asparagine was also
      severely detrimental to catalysis. The relative position of this residue within
      the active site and dependence of function on acidic character point toward a
      critical role for aspartate 280 in activation of the substrate and the catalytic
      cysteine. Finally, changing lysine 339 to alanine yielded the wild-type Vmax, but
      a 165-fold decrease in affinity for UDP-glucose. Interestingly, gel filtration of
      this substrate-binding mutant also determined it was a dimer, indicating that
      hexameric quaternary structure is not critical for catalysis. Collectively, this
      analysis has provided novel insights into the complex catalytic mechanism of
      UGDH.

PMID- 17209548
TI  - Investigating the geminal diamine intermediate of Yersinia pestis arginine
      decarboxylase with substrate, product, and inhibitors using single wavelength
      stopped-flow spectroscopy.
AB  - The reaction mechanism of Yersinia pestis arginine decarboxylase has been
      investigated using a series of substrate, product, and inhibitors. Using single
      wavelength stopped-flow spectroscopy, novel mechanistic features were noted in
      the presence of the product, agmatine. By focusing on the excitation and emission
      wavelengths of the geminal diamine intermediate, we were able to monitor the
      formation and decay of two different geminal diamine species. Experiments
      revealed that the enzyme exists in two different conformational states--one that
      binds ligand and one that does not. The on and off rates for the conversion
      between the two conformational states was determined to be 390 s-1 and 880 s-1,
      respectively. The KD for agmatine binding was 6 mM. In addition, experiments
      revealed a pH-dependent conversion between two states of the enzyme. The
      deprotonated form of the enzyme binds ligand more slowly than the protonated
      form. The rates for the formation of the geminal diamine and external aldimine in
      this pathway were determined to be 25 and 4 s-1, respectively. There is also a
      slow interconversion between the protonated and deprotonated enzymes that has a
      pKa of approximately 8.0. Finally, the formation of the geminal diamine was
      determined to be Mg2+-dependent.

PMID- 17209549
TI  - Resolving the fluorescence response of Escherichia coli carbamoyl phosphate
      synthetase: mapping intra- and intersubunit conformational changes.
AB  - Carbamoyl phosphate synthetase (CPS) from Escherichia coli is potentially
      overlaid with a network of allosterism, interconnecting active sites, effector
      binding sites, and aggregate interfaces to control its mechanisms of catalytic
      synchronization, regulation, and oligomerization, respectively. To characterize
      these conformational changes, a tryptophan-free variant of CPS was genetically
      engineered by substituting six native tryptophans with tyrosines. Each tryptophan
      was then reinserted, singly, as a specific fluorescence probe of its
      corresponding microenvironment. The amino acid substitutions themselves result in
      little apparent disruption of the protein; variants maintain catalytic and
      allosteric functionality, and the fluorescence properties of each tryptophan,
      while unique, are additive to wild-type CPS. Whereas the collective, intrinsic
      fluorescence response of E. coli CPS is largely insensitive to ligand binding,
      changes of the individual probes in intensity, lifetime, anisotropy, and
      accessibility to acrylamide quenching highlight the dynamic interplay between
      several protein domains, as well as between subunits. W213 within the carboxy
      phosphate domain, for example, exhibits an almost 40% increase in intensity upon
      saturation with ATP; W437 of the oligomerization domain, in contrast, is
      essentially silent in its fluorescence to the binding of ligands. Nucleotide and
      bicarbonate association within the large subunit induces fluorescence changes in
      both W170 and W175 of the small subunit, indicative of the type of long-range
      interactions purportedly synchronizing the carboxy phosphate and amidotransferase
      domains of the enzyme to initiate catalysis. ATP and ADP engender different
      fluorescence responses in most tryptophans, perhaps reflecting coordinating,
      conformational changes accompanying the cycling of reactants and products during
      catalysis.

PMID- 17209550
TI  - Kinetic evidence supports the existence of two halide binding sites that have a
      distinct impact on the heme iron microenvironment in myeloperoxidase.
AB  - Myeloperoxidase (MPO) structural analysis has suggested that halides and
      pseudohalides bind to the distal binding site and serve as substrates or
      inhibitors, while others have concluded that there are two separate sites. Here,
      evidence for two distinct binding sites for halides comes from the bell-shaped
      effects observed when the second-order rate constant of nitric oxide (NO) binding
      to MPO was plotted versus Cl- concentration. The chloride level used in the X-ray
      structure that produced Cl- binding to the amino terminus of the helix halide
      binding site was insufficient to populate either of the two sites that appear to
      be responsible for the two phases. Biphasic effects were also observed when the I
      , Br-, and SCN- concentrations were plotted against the NO combination rate
      constants. Interestingly, the trough concentrations obtained from the bell-shaped
      curves are comparable to normal plasma levels of halides and pseudohalides,
      suggesting the potential relevance of these molecules in modulating MPO function.
      The second-order rate constant of NO binding in the presence of plasma levels of
      I-, Br-, and SCN- is 1-2-fold lower compared to that obtained in the absence of
      these molecules and remains unaltered through the Cl- plasma level. When Cl-
      exceeded the plasma level, the NO combination rate becomes indistinguishable from
      the second phase of the bell-shaped curve that was obtained in the absence of
      halides. Our results are consistent with two halide binding sites that could be
      populated by two halides in which both display distinct effects on the MPO heme
      iron microenvironment.

PMID- 17209551
TI  - The potential role of nitric oxide in substrate switching in eosinophil
      peroxidase.
AB  - Eosinophil recruitment and enhanced nitric oxide (NO) production are
      characteristic features of asthma and other airway diseases. Eosinophil
      peroxidase (EPO), a highly cationic hemoprotein secreted by activation of
      eosinophils, is believed to play a central role in host defense against invading
      pathogens. The enzyme uses hydrogen peroxide (H2O2) and bromide (Br-), a
      preferred cosubstrate of EPO, to generate the cytotoxic oxidant hypobromous acid.
      The aim of this work was to determine whether NO can compete with plasma levels
      of Br- and steer the enzyme reaction from a 2e- oxidation to a 1e- oxidation
      pathway. Rapid kinetic measurements were utilized to measure the rate of EPO
      compounds I and II formation, duration, and decay at 412 and 432 nm,
      respectively, at 10 degrees C. An EPO-Fe(III) solution supplemented with
      increasing Br- concentrations was rapidly mixed with fixed amounts of H2O2 in the
      absence and in the presence of increasing NO concentrations. In the absence of
      NO, EPO-Fe(III) primarily converted to compound I and, upon H2O2 exhaustion, it
      decayed rapidly to the ferric form. NO caused a significant increase in the
      accumulation of EPO compound II, along with a proportional increase in its rate
      of formation and duration as determined by the time elapsed during catalysis. The
      time courses for these events have been incorporated into a comprehensive kinetic
      model. Computer simulations carried out supported the involvement of a
      conformational intermediate in the EPO compound II complex decay. Collectively,
      our results demonstrated that NO displays the potential capacity to promote
      substrate switching by modulating substrate selectivity of EPO.

PMID- 17209552
TI  - Structural basis for the photochemistry of alpha-phycoerythrocyanin.
AB  - Phycobiliproteins and phytochromes are light-harvesting and light-sensing
      proteins containing linear tetrapyrroles, so-called bile chromophores. The
      chromophores in certain biliproteins, including the phytochromes, isomerize
      reversibly from a stable Z-configuration to a stable E-configuration when
      irradiated with light of the appropriate wavelength. Here, we report the crystal
      structure of alpha-phycoerythrocyanin with its chromophore in the E
      configuration, compare it with the Z-configuration found in trimeric
      phycoerythrocyanin, and reveal the structural bases of the isomerization. The
      geometric changes of the chromophore account for the large spectral shift, which
      characterizes the overall transition. Interactions of the chromophore A and D
      pyrrole rings with flexible protein moieties are required for the formation and
      stabilization of the isomers. We predict that the results will hold for all
      photoactive biliproteins.

PMID- 17209553
TI  - Pre-steady-state kinetic study of substrate specificity of Escherichia coli
      formamidopyrimidine--DNA glycosylase.
AB  - Formamidopyrimidine-DNA glycosylase (Fpg) is responsible for removal of 8
      oxoguanine (8-oxoG) and other oxidized purine lesions from DNA and can also
      excise some oxidatively modified pyrimidines [such as dihydrouracil (DHU)]. Fpg
      is also specific for a base opposite the lesion, efficiently excising 8-oxoG
      paired with C but not with A. We have applied stopped-flow kinetics using
      intrinsic tryptophan fluorescence of the enzyme and fluorescence of 2-aminopurine
      labeled DNA to analyze the conformational dynamics of Escherichia coli Fpg during
      processing of good substrates (8-oxoG.C), poor substrates (8-oxoG.A), and
      substrates of unclear specificity (such as DHU and 8-oxoG opposite T or G). The
      analysis of fluorescence traces allows us to conclude that when the enzyme
      encounters its true substrate, 8-oxoG.C, the complex enters the productive
      catalytic reaction after approximately 50 ms, partitioning the substrate away
      from the competing dissociation process, while poor substrates linger in the
      initial encounter complex for longer. Several intermediate ES complexes were
      attributed to different structures that exist along the reaction pathway. A
      likely sequence of events is that the damaged base is first destabilized by the
      enzyme binding and then everted from DNA, followed by insertion of several amino
      acid residues into DNA and isomerization of the enzyme into a pre-excision
      complex. We conclude that rejection of the incorrect substrates occurs mostly at
      the early stage of formation of the pre-eversion recognition complex, supporting
      the role of indirect readout in damage recognition.

PMID- 17209554
TI  - Crystal structures, metal activation, and DNA-binding properties of two-domain
      IdeR from Mycobacterium tuberculosis.
AB  - The iron-dependent regulator IdeR is a key transcriptional regulator of iron
      uptake in Mycobacterium tuberculosis. In order to increase our insight into the
      role of the SH3-like third domain of this essential regulator, the metal-binding
      and DNA-binding properties of two-domain IdeR (2D-IdeR) whose SH3-like domain has
      been truncated were characterized. The equilibrium dissociation constants for
      Co2+ and Ni2+ activation of 2D-IdeR for binding to the fxbA operator and the DNA
      binding affinities of 2D-IdeR in the presence of excess metal ions were estimated
      using fluorescence spectroscopy. 2D-IdeR binds to fxbA operator DNA with similar
      affinity as full-length IdeR in the presence of excess metal ion. However, the
      Ni2+ concentrations required to activate 2D-IdeR for DNA binding appear to be
      smaller than that for full-length IdeR while the concentration of Co2+ required
      for activation remains the same. We have determined the crystal structures of
      Ni2+-activated 2D-IdeR at 1.96 A resolution and its double dimer complex with the
      mbtA-mbtB operator DNA in two crystal forms at 2.4 A and 2.6 A, the highest
      resolutions for DNA complexes for any structures of iron-dependent regulator
      family members so far. The 2D-IdeR-DNA complex structures confirm the specificity
      of Ser37 and Pro39 for thymine bases and suggest preferential contacts of Gln43
      to cytosine bases of the DNA. In addition, our 2D-IdeR structures reveal a
      remarkable property of the TEV cleavage sequence remaining after removal of the C
      terminal His6. This C-terminal tail promotes crystal contacts by forming a beta
      sheet with the corresponding tail of neighboring subunits in two unrelated
      structures of 2D-IdeR, one with and one without DNA. The contact-promoting
      properties of this C-terminal TEV cleavage sequence may be beneficial for
      crystallizing other proteins.

PMID- 17209555
TI  - Human DNA polymerase alpha uses a combination of positive and negative
      selectivity to polymerize purine dNTPs with high fidelity.
AB  - DNA polymerases accurately replicate DNA by incorporating mostly correct dNTPs
      opposite any given template base. We have identified the chemical features of
      purine dNTPs that human pol alpha uses to discriminate between right and wrong
      dNTPs. Removing N-3 from guanine and adenine, two high-fidelity bases,
      significantly lowers fidelity. Analogously, adding the equivalent of N-3 to low
      fidelity benzimidazole-derived bases (i.e., bases that pol alpha rapidly
      incorporates opposite all four natural bases) and to generate 1-deazapurines
      significantly strengthens the ability of pol alpha to identify the resulting 1
      deazapurines as wrong. Adding the equivalent of the purine N-1 to benzimidazole
      or to 1-deazapurines significantly decreases the rate at which pol alpha
      polymerizes the resulting bases opposite A, C, and G while simultaneously
      enhancing polymerization opposite T. Conversely, adding the equivalent of
      adenine's C-6 exocyclic amine (N-6) to 1- and 3-deazapurines also enhances
      polymerization opposite T but does not significantly decrease polymerization
      opposite A, C, and G. Importantly, if the newly inserted bases lack N-1 and N-6,
      pol alpha does not efficiently polymerize the next correct dNTP, whereas if it
      lacks N-3, one additional nucleotide is added and then chain termination ensues.
      These data indicate that pol alpha uses two orthogonal screens to maximize its
      fidelity. During dNTP polymerization, it uses a combination of negative (N-1 and
      N-3) and positive (N-1 and N-6) selectivity to differentiate between right and
      wrong dNTPs, while the shape of the base pair is essentially irrelevant. Then, to
      determine whether to add further dNTPs onto the just added nucleotide, pol alpha
      appears to monitor the shape of the base pair at the primer 3'-terminus. The
      biological implications of these results are discussed.

PMID- 17209556
TI  - Modifying the beta,gamma leaving-group bridging oxygen alters nucleotide
      incorporation efficiency, fidelity, and the catalytic mechanism of DNA polymerase
      beta.
AB  - DNA polymerase catalysis and fidelity studies typically compare incorporation of
      "right" versus "wrong" nucleotide bases where the leaving group is pyrophosphate.
      Here we use dGTP analogues replacing the beta,gamma-bridging O with CH2, CHF,
      CF2, or CCl2 to explore leaving-group effects on the nucleotidyl transfer
      mechanism and fidelity of DNA polymerase (pol) beta. T.G mismatches occur with
      fidelities similar to dGTP with the exception of the CH2 analogue, which is
      incorporated with 5-fold higher fidelity. All analogues are observed to bind
      opposite template C with Kds between 1 and 4 microM, and structural evidence
      suggests that the analogues bind in essentially the native conformation, making
      them suitable substrates for probing linear free energy relationships (LFERs) in
      transient-kinetics experiments. Importantly, Brnsted correlations of log(kpol)
      versus leaving-group pKa for both right and wrong base incorporation reveal
      similar sensitivities (betalg approximately -0.8) followed by departures from
      linearity, suggesting that a chemical step rather than enzyme conformational
      change is rate-limiting for either process. The location of the breaks relative
      to pKas of CF2, O, and the sterically bulky CCl2-bridging compounds suggests a
      modification-induced change in the mechanism by stabilization of leaving-group
      elimination. The results are addressed theoretically in terms of the energetics
      of successive primer 3'-O addition (bond forming) and pyrophosphate analogue
      elimination (bond breaking) reaction energy barriers.

PMID- 17209557
TI  - Dopamine affects the stability, hydration, and packing of protofibrils and
      fibrils of the wild type and variants of alpha-synuclein.
AB  - Parkinson's disease (PD) is characterized by the presence of cytoplasmic
      inclusions composed of alpha-synuclein (alpha-syn) in dopaminergic neurons. This
      suggests a pivotal role of dopamine (DA) on PD development. Here, we show that DA
      modulates differently the stability of protofibrils (PF) and fibrils (F) composed
      of wild type or variants of alpha-syn (A30P and A53T) as probed by high
      hydrostatic pressure (HHP). While in the absence of DA, all alpha-syn PF
      exhibited identical stability, in its presence, the variant-composed PF acquired
      a greater stability (DAPFwt < DAPFA30P = DAPFA53T), implying that they would last
      longer, which could shed light onto why these mutations are so aggressive. When
      alpha-syn was incubated for long times (18 days) in the presence of DA, we
      observed the formation of F by electronic microscopy, suggesting that the PF
      trapped in the presence of DA in short times can evolve into F. The stability of
      F was also altered by DA. DAFwt was more labile than Fwt, indicating that the
      former would be more susceptible to breakage. PFA30P and DAPFA30P, when added to
      mesencephalic and cortical neurons in culture, decreased the number and length of
      neurites and increased the number of apoptotic cells. Surprisingly, these toxic
      effects of PFA30P and DAPFA30P were practically abolished with HHP treatment,
      which was able to break the PF into smaller aggregates, as seen by atomic force
      microscopy. These results suggest that strategies aimed at breaking and/or
      clearing these aggregates is promising in alleviating the symptoms of PD.

PMID- 17209558
TI  - Redox-induced changes in flavin structure and roles of flavin N(5) and the
      ribityl 2'-OH group in regulating PutA--membrane binding.
AB  - PutA is a novel flavoprotein in Escherichia coli that switches from a
      transcriptional repressor to a membrane-bound proline catabolic enzyme. Previous
      crystallographic studies of the PutA proline dehydrogenase (PRODH) domain under
      oxidizing conditions revealed that FAD N(5) and the ribityl 2'-OH group form
      hydrogen bonds with Arg431 and Arg556, respectively. Here we identify molecular
      interactions in the PutA PRODH active site that underlie redox-dependent
      functional switching of PutA. We report that reduction of the PRODH domain
      induces major structural changes in the FAD cofactor, including a 22 degrees bend
      of the isoalloxazine ring along the N(5)-N(10) axis, crankshaft rotation of the
      upper part of the ribityl chain, and formation of a new hydrogen bond network
      involving the ribityl 2'-OH group, FAD N(1), and Gly435. The roles of the FAD 2'
      OH group and the FAD N(5)-Arg431 hydrogen bond pair in regulating redox-dependent
      PutA-membrane associations were tested using FAD analogues and site-directed
      mutagenesis. Kinetic membrane binding measurements and cell-based reporter gene
      assays of modified PutA proteins show that disrupting the FAD N(5)-Arg431
      interaction impairs the reductive activation of PutA-membrane binding. We also
      show that the FAD 2'-OH group acts as a redox-sensitive toggle switch that
      controls PutA-membrane binding. These results illustrate a new versatility of the
      ribityl chain in flavoprotein mechanisms.

PMID- 17209559
TI  - Interaction of arginine-rich peptides with membrane-associated proteoglycans is
      crucial for induction of actin organization and macropinocytosis.
AB  - Arginine-rich peptides, including octaarginine (R8), HIV-1 Tat, and branched
      chain arginine-rich peptides, belong to one of the major classes of cell
      permeable peptides which deliver various proteins and macromolecules to cells.
      The importance of the endocytic pathways has recently been demonstrated in the
      cellular uptake of these peptides. We have previously shown that macropinocytosis
      is one of the major pathways for cellular uptake and that organization of the F
      actin accompanies this process. In this study, using proteoglycan-deficient CHO
      cells, we have demonstrated that the membrane-associated proteoglycans are
      indispensable for the induction of the actin organization and the macropinocytic
      uptake of the arginine-rich peptides. We have also demonstrated that the cellular
      uptake of the Tat peptide is highly dependent on heparan sulfate proteoglycan
      (HSPG), whereas the R8 peptide uptake is less dependent on HSPG. This suggests
      that the structure of the peptides may determine the specificity for HSPG, and
      that HSPG is not the sole receptor for macropinocytosis. Comparison of the HSPG
      specificity of the branched-chain arginine-rich peptides in cellular uptake has
      suggested that the charge density of the peptides may determine the specificity.
      The activation of the Rac protein and organization of the actin were observed
      within a few minutes after the peptide treatment. These data strongly suggest the
      possibility that the interaction of the arginine-rich peptides with the membrane
      associated proteoglycans quickly activates the intracellular signals and induces
      actin organization and macropinocytotis.

PMID- 17209560
TI  - Sequential degradation of alphaII and betaII spectrin by calpain in glutamate or
      maitotoxin-stimulated cells.
AB  - Calpain-catalyzed proteolysis of II-spectrin is a regulated event associated with
      neuronal long-term potentiation, platelet and leukocyte activation, and other
      processes. Calpain proteolysis is also linked to apoptotic and nonapoptotic cell
      death following excessive glutamate exposure, hypoxia, HIV-gp120/160 exposure, or
      toxic injury. The molecular basis for these divergent consequences of calpain
      action, and their relationship to spectrin proteolysis, is unclear. Calpain
      preferentially cleaves II spectrin in vitro in repeat 11 between residues Y1176
      and G1177. Unless stimulated by Ca++ and calmodulin (CaM), betaII spectrin
      proteolysis in vitro is much slower. We identify additional unrecognized sites in
      spectrin targeted by calpain in vitro and in vivo. Bound CaM induces a second II
      spectrin cleavage at G1230*S1231. BetaII spectrin is cleaved at four sites. One
      cleavage only occurs in the absence of CaM at high enzyme-to-substrate ratios
      near the betaII spectrin COOH-terminus. CaM promotes II spectrin cleavages at
      Q1440*S1441, S1447*Q1448, and L1482*A1483. These sites are also cleaved in the
      absence of CaM in recombinant II spectrin fusion peptides, indicating that they
      are probably shielded in the spectrin heterotetramer and become exposed only
      after CaM binds alphaII spectrin. Using epitope-specific antibodies prepared to
      the calpain cleavage sites in both alphaII and betaII spectrin, we find in
      cultured rat cortical neurons that brief glutamate exposure (a physiologic
      ligand) rapidly stimulates alphaII spectrin cleavage only at Y1176*G1177, while
      II spectrin remains intact. In cultured SH-SY5Y cells that lack an NMDA receptor,
      glutamate is without effect. Conversely, when stimulated by calcium influx (via
      maitotoxin), there is rapid and sequential cleavage of alphaII and then betaII
      spectrin, coinciding with the onset of nonapoptotic cell death. These results
      identify (i) novel calpain target sites in both alphaII and betaII spectrin; (ii)
      trans-regulation of proteolytic susceptibility between the spectrin subunits in
      vivo; and (iii) the preferential cleavage of alphaII spectrin vs betaII spectrin
      when responsive cells are stimulated by engagement of the NMDA receptor. We
      postulate that calpain proteolysis of spectrin can activate two physiologically
      distinct responses: one that enhances skeletal plasticity without destroying the
      spectrin-actin skeleton, characterized by preservation of betaII spectrin; or an
      alternative response closely correlated with nonapoptotic cell death and
      characterized by proteolysis of betaII spectrin and complete dissolution of the
      spectrin skeleton.

PMID- 17209561
TI  - NMR structural investigation of the mitochondrial outer membrane protein VDAC and
      its interaction with antiapoptotic Bcl-xL.
AB  - Bcl-2 family proteins are essential regulators of cell death and exert their
      primary pro- or antiapoptotic roles at the mitochondrial outer membrane.
      Previously, pro- and antiapoptotic Bcl-2 proteins have been shown to interact
      with the voltage-dependent anion channel (VDAC) of the outer mitochondrial
      membrane. VDAC is a 283-residue integral membrane protein that forms an aqueous
      pore in the outer mitochondrial membrane, through which metabolites and other
      small molecules pass between the cytosol and intermembrane space. The essential
      life-sustaining function of VDAC in metabolite trafficking is believed to be
      regulated by proteins of the Bcl-2 family. The protective role of antiapoptotic
      Bcl-xL may be through its interaction with VDAC. Here, VDAC has been expressed,
      purified, and refolded into a functional form amenable to NMR studies. Various
      biophysical experiments indicate that micelle-bound VDAC is in intermediate
      exchange between monomer and trimer. Using NMR spectroscopy, gel filtration, and
      chemical cross-linking, we obtained direct evidence for binding of Bcl-xL to VDAC
      in a detergent micelle system. The VDAC-interacting region of Bcl-xL was
      characterized by NMR with chemical shift perturbation and transferred cross
      saturation. The interaction region was mapped to a putative helical hairpin motif
      of Bcl-xL that was found to insert into detergent micelles. Our results suggest
      that Bcl-xL can bind to one or two VDAC molecules forming heterodimers and
      heterotrimers. Our characterization of the VDAC/Bcl-xL complex offers initial
      structural insight into the role of antiapoptotic Bcl-xL in regulating apoptotic
      events in the mitochondrial outer membrane.

PMID- 17209562
TI  - Role of the conserved arginine 274 and histidine 224 and 228 residues in the
      NuoCD subunit of complex I from Escherichia coli.
AB  - The conserved arginine 274 and histidine 224 and 228 residues in subunit NuoCD of
      complex I from Escherichia coli were substituted for alanine. The wild-type and
      mutated NuoCD subunit was expressed on a plasmid in an E. coli strain bearing a
      nuoCD deletion. Complex I was fully expressed in the H224A and H228A mutants,
      whereas the R274A mutation yielded approximately 50% expression. Ubiquinone
      reductase activity of complex I was studied in membranes and with purified enzyme
      and was 50% and 30% of the wild-type activity in the H224A and H228A mutants,
      respectively. The activity of R274A was less than 5% of the wild type in
      membranes but 20% in purified complex I. Rolliniastatin inhibited quinone
      reductase activity in the mutants with similar affinity as in the wild type,
      indicating that the quinone-binding site was not significantly altered by the
      mutations. Ubiquinone-dependent superoxide production by complex I was similar to
      the wild type in the R274A mutant but slightly higher in the H224A and H228A
      mutants. The EPR spectra of purified complex I from the H224A and H228A mutants
      did not differ from the wild type. In contrast, the signals of the N2 cluster and
      another fast-relaxing [4Fe-4S] cluster, tentatively assigned as N6b, were
      drastically decreased in the NADH-reduced R274A mutant enzyme but reappeared on
      further reduction with dithionite. These findings show that the redox potential
      of the N2 and N6b centers is shifted to more negative values by the R274A
      mutation. Purified complex I was reconstituted into liposomes, and electric
      potential was generated across the membrane upon NADH addition in all three
      mutant enzymes, suggesting that none of the mutations directly affect the proton
      pumping machinery.

PMID- 17209563
TI  - Oxyferryl heme and not tyrosyl radical is the likely culprit in prostaglandin H
      synthase-1 peroxidase inactivation.
AB  - Prostaglandin H synthase-1 (PGHS-1) is a bifunctional heme protein catalyzing
      both a peroxidase reaction, in which peroxides are converted to alcohols, and a
      cyclooxygenase reaction, in which arachidonic acid is converted into
      prostaglandin G2. Reaction of PGHS-1 with peroxide forms Intermediate I, which
      has an oxyferryl heme and a porphyrin radical. An intramolecular electron
      transfer from Tyr385 to Intermediate I forms Intermediate II, which contains two
      oxidants: an oxyferryl heme and the Tyr385 radical required for cyclooxygenase
      catalysis. Self-inactivation of the peroxidase begins with Intermediate II, but
      it has been unclear which of the two oxidants is involved. The kinetics of
      tyrosyl radical, oxyferryl heme, and peroxidase inactivation were examined in
      reactions of PGHS-1 reconstituted with heme or mangano protoporphyrin IX with a
      lipid hydroperoxide, 15-hydroperoxyeicosatetraenoic acid (15-HPETE), and ethyl
      hydrogen peroxide (EtOOH). Tyrosyl radical formation was significantly faster
      with 15-HPETE than with EtOOH and roughly paralleled oxyferryl heme formation at
      low peroxide levels. However, the oxyferryl heme intensity decayed much more
      rapidly than the tyrosyl radical intensity at high peroxide levels. The rates of
      reactions for PGHS-1 reconstituted with MnPPIX were approximately an order of
      magnitude slower, and the initial species formed displayed a wide singlet (WS)
      radical, rather than the wide doublet radical observed with PGHS-1 reconstituted
      with heme. Inactivation of the peroxidase activity during the reaction of PGHS-1
      with EtOOH or 15-HPETE correlated with oxyferryl heme decay, but not with changes
      in tyrosyl radical intensity or EPR line shape, indicating that the oxyferryl
      heme, and not the tyrosyl radical, is responsible for the self-destructive
      peroxidase side reactions. Computer modeling to a minimal mechanism was
      consistent with oxyferryl heme being the source of peroxidase inactivation.

PMID- 17209564
TI  - Role of flavin mononucleotide in the thermostability and oligomerization of
      Escherichia coli stress-defense protein WrbA.
AB  - WrbA is an oligomeric flavodoxin-like protein that binds one molecule of flavin
      mononucleotide (FMN) per monomer and whose redox activity is implicated in
      oxidative stress defense. WrbA thermostability and oligomerization in the
      presence and absence of bound FMN were investigated using complementary
      biophysical methods. Infrared spectroscopy indicates similar structures for apo
      and holoWrbA. FMN binding has a dramatic effect on WrbA thermal stability,
      shifting the Tm by approximately 40 degrees C. Upon denaturation, the protein
      forms insoluble aggregates that lack native secondary structure and have no bound
      FMN. Circular dichroism (CD) reveals that the thermal unfolding of apo and
      holoWrbA proceeds via the formation of an aggregation-prone intermediate that
      retains substantial secondary structure but has lost the native configuration of
      the active site. This intermediate persists in solution up to 100 degrees C at
      micromolar concentrations. A similar partially folded state is populated during
      chemical denaturation with guanidinium chloride, but accumulation of the
      intermediate is evident only in the absence of FMN. The results also suggest that
      WrbA maintains some interaction with FMN in its partially folded state, despite
      the loss of the induced CD signal of FMN. On the basis of these data, the
      unfolding process can be depicted as follows: native holoprotein -->
      holointermediate --> apointermediate --> insoluble aggregate. Mass spectrometry
      shows that FMN promotes WrbA association into tetramers, which are more
      thermoresistant than dimers or monomers, suggesting that multimerization
      underlies the FMN effect on WrbA thermostability. This study illustrates the
      utility of analyzing conformational transitions and intermolecular interactions
      using methods that probe the liquid, solid, and gas phases.

PMID- 17209565
TI  - Time-dependent inhibition of isoprenylcysteine carboxyl methyltransferase by
      indole-based small molecules.
AB  - Isoprenylcysteine carboxyl methyltransferase (Icmt) catalyzes the methylation of
      the C-terminal prenylcysteine found on prenylated proteins. Numerous studies have
      shown that the methylation step is important for the correct localization and
      function of many prenylated proteins, most notably GTPases in the Ras
      superfamily. We recently reported identification of a small molecule derived from
      an indole core as a potent, cell-active inhibitor of Icmt whose potency was
      increased upon preincubation with the enzyme [Winter-Vann, A. M., Baron, R. A.,
      et al. (2005) Proc. Natl. Acad. Sci. U.S.A. 102 (12), 4336-41]. In the study
      presented here, we performed a kinetic characterization of this time-dependent
      inhibition of Icmt by 2-[5-(3-methylphenyl)-1-octyl-1H-indol-3-yl]acetamide
      (cysmethynil). These analyses revealed that cysmethynil is a competitive
      inhibitor with respect to the isoprenylated cysteine substrate and a
      noncompetitive inhibitor with respect to AdoMet, the methyl donor in the
      reaction. The Ki of cysmethynil for Icmt, which represents the dissociation
      constant of the initial complex with the enzyme, was 2.39 +/- 0.02 microM, and
      the Ki*, which is the overall dissociation constant of the inhibitor for the
      final complex, was 0.14 +/- 0.01 microM. The first-order rate constant for the
      conversion of the initial enzyme-inhibitor complex to the final high-affinity
      complex was 0.87 +/- 0.06 min-1, and that for the reverse process was 0.053 +/-
      0.003 min-1; the latter rate constant corresponds to a half-life for the high
      affinity complex of 15 min. Structure-activity relationships of a number of
      closely related indole compounds revealed that the hydrophobicity of the
      substituent on the nitrogen of the indole core was responsible for the
      manifestation of time-dependent inhibition. These findings markedly enhance our
      understanding of the mechanism of inhibition of Icmt by this indole class of
      compounds and should facilitate ongoing efforts to assess the potential of
      targeting this enzyme in anticancer drug design.

PMID- 17209566
TI  - Probing DNA bulges with designed helical spirocyclic molecules.
AB  - Because bulged structures (unpaired bases) in nucleic acids are of general
      biological significance, it has been of interest to design small molecules as
      specific probes of bulge function. On the basis of our earlier work with the
      specific DNA bulge-binding metabolite obtained from the enediyne antitumor
      antibiotic neocarzinostatin chromophore (NCS-chrom), we have prepared three small
      helical spirocyclic molecules that most closely mimic the natural product. These
      wedge-shaped molecules resemble the natural product in having the sugar residue
      attached to the same five-membered ring system. In one instance, the sugar is
      aminoglucose in beta-glycosidic linkage, and in the other, two enantiomers have
      the natural sugar N-methylfucosamine in alpha-glycosidic linkage. All three
      analogues were found to interfere with bulge-specific cleavage by NCS-chrom and
      the ability of bulged DNA to serve as a template for DNA polymerase 1 in
      accordance with their binding affinities for DNA containing a two-base bulge.
      Comparable results were obtained with the analogues for the less efficiently
      cleaved three-base bulge DNA structures. In each situation, the enantiomers
      possessing the natural sugar in alpha-glycosidic linkage are the most potent
      inhibitors of the cleavage reaction. In the DNA polymerase reactions, again, the
      closest natural product mimics were the most effective in selectively impeding
      nucleotide extension at the bulge site, presumably by complex formation. These
      results demonstrate the potential usefulness of bulge-binding compounds in
      modifying DNA structure and function and support efforts to design and prepare
      reactive species of these molecules that can covalently modify bulged DNA.

PMID- 17209567
TI  - Coupled ATP and DNA binding of adeno-associated virus Rep40 helicase.
AB  - Adeno-associated virus 2 Rep40 helicase is involved in packaging single-stranded
      genomic DNA into virions. ATPase activity was stimulated 5-10-fold by DNA,
      depending upon assay conditions. The concentration dependence of Rep40 ATPase
      activity in the absence and presence of DNA indicates that the monomer is
      inactive and that the active enzyme is at least a dimer. Binding to
      oligonucleotides, examined by fluorescence anisotropy, was positively cooperative
      and required ATP or ATPgammaS; ADP and AMPPCP did not promote binding. The
      cooperativity and the nucleotide requirement were also demonstrated by surface
      plasmon resonance. Although the Rep40 behaves as a monomer in solution, it binds
      to DNA as an oligomer. The requirement of a nucleotide for DNA binding and the
      stimulation of ATPase activity by DNA indicate that the two processes are linked.
      Glutaraldehyde cross-linking generated a species that migrates as a trimer on
      sodium dodecyl sulfate (SDS) gel electrophoresis; ATPS promoted the formation of
      this species and higher order oligomers. The predominant cross-linked species was
      a trimer in the absence of ATPgammaS, regardless of whether duplex or single
      stranded DNA was present. In the presence of duplex or single-stranded DNA and
      ATPgammaS, glutaraldehyde cross-linking generated a species that behaved as a
      dimer on SDS gel elctrophoresis. Sucrose-gradient velocity sedimentation of Rep40
      gave an S20,w of 3 in the absence of ligands or in the presence of a 26 bp duplex
      DNA. The S20,w was 3.5 in the presence of ATPgammaS and 7 and 7.6 in the presence
      of DNA and ATPgammaS.

PMID- 17209568
TI  - Characterization of TDP-4-keto-6-deoxy-D-glucose-3,4-ketoisomerase from the D
      mycaminose biosynthetic pathway of Streptomyces fradiae: in vitro activity and
      substrate specificity studies.
AB  - Deoxysugars are critical structural elements for the bioactivity of many natural
      products. Ongoing work on elucidating a variety of deoxysugar biosynthetic
      pathways has paved the way for manipulation of these pathways for the generation
      of structurally diverse glycosylated natural products. In the course of this
      work, the biosynthesis of d-mycaminose in the tylosin pathway of Streptomyces
      fradiae was investigated. Attempts to reconstitute the entire mycaminose
      biosynthetic machinery in a heterologous host led to the discovery of a
      previously overlooked gene, tyl1a, encoding an enzyme thought to convert TDP-4
      keto-6-deoxy-d-glucose to TDP-3-keto-6-deoxy-d-glucose, a 3,4-ketoisomerization
      reaction in the pathway. Tyl1a has now been overexpressed, purified, and assayed,
      and its activity has been verified by product analysis. Incubation of Tyl1a and
      the C-3 aminotransferase TylB, the next enzyme in the pathway, produced TDP-3
      amino-3,6-dideoxy-d-glucose, confirming that these two enzymes act sequentially.
      Steady state kinetic parameters of the Tyl1a-catalyzed reaction were determined,
      and the ability of Tyl1a and TylB to process a C-2 deoxygenated substrate and a
      CDP-linked substrate was also demonstrated. Enzymes catalyzing 3,4
      ketoisomerization of hexoses represent a new class of enzymes involved in unusual
      sugar biosynthesis. The fact that Tyl1a exhibits a relaxed substrate specificity
      holds potential for future deoxysugar biosynthetic engineering endeavors.

PMID- 17209569
TI  - The two-domain structure of 5'-adenylylsulfate (APS) reductase from Enteromorpha
      intestinalis is a requirement for efficient APS reductase activity.
AB  - 5'-Adenylylsulfate (APS) reductase from Enteromorpha intestinalis (EiAPR) is
      composed of two domains that function together to reduce APS to sulfite. The
      carboxyl-terminal domain functions as a glutaredoxin that mediates the transfer
      of electrons from glutathione to the APS reduction site on the amino-terminal
      domain. To study the basis for the interdomain interaction, a heterologous system
      was constructed in which the C domain of EiAPR was fused to the carboxyl terminus
      of the APS reductase from Pseudomonas aeruginosa (PaAPR), an enzyme that normally
      uses thioredoxin as an electron donor and is incapable of using glutathione for
      this function. The hybrid enzyme, which retains the [4Fe-4S] cluster from PaAPR,
      was found to use both thioredoxin and glutathione as an electron donor for APS
      reduction. The ability to use glutathione was enhanced by the addition of Na2SO4
      to the reaction buffer, a property that the hybrid enzyme shares with EiAPR. When
      the C domain was added as a separate component, it was much less efficient in
      conferring PaAPR with the ability to use glutathione as an electron donor,
      despite the fact that the separately expressed C domain functioned in two
      activities that are typical for glutaredoxins, hydroxyethyl disulfide reduction
      and electron donation to ribonucleotide reductase. These results suggest that the
      physical connection of the reductase and C domain on a single polypeptide is
      critical for the electron-transfer reaction. Moreover, the effect of Na2SO4
      suggests that a water-ordering component of the reaction milieu is critical for
      the catalytic function of plant-type APS reductases by promoting the interdomain
      interaction.

PMID- 17209570
TI  - Isomers of human alpha-synuclein stabilized by disulfide bonds exhibit distinct
      structural and aggregative properties.
AB  - The discovery of three mutants in the -synuclein (alphaSyn) gene and the
      identification of alphaSyn as the major component of Lewy body have opened a new
      field for understanding the pathogenesis of Parkinson's disease (PD). AlphaSyn is
      a natively unfolded protein with unknown function and unspecified conformational
      heterogeneity. In this study, we introduce four Ser/Ala --> Cys mutations at
      positions 9, 42, 69, and 89 in human wild-type alphaSyn (wt-alphaSyn) and two PD
      associated alphaSyn mutants, A30P-alphaSyn and A53T-alphaSyn. This allows
      expression of three alphaSyn mutants, wt-alphaSyn(4C), A30P-alphaSyn(4C), and
      A53T-Syn(4C). Subsequent oxidative folding enables each alphaSyn(4C) mutant to
      form three partially stabilized two-disulfide isomers, designated as
      alphaSyn(2SS), that are amenable to further isolation and characterization. These
      alphaSyn mutants exhibit the following properties. (a) A30P-alphaSyn(4C) exhibits
      a lower folding flexibility than wt-alphaSyn(4C) and A53T-alphaSyn(4C). (b) All
      three alphaSyn(4C) mutants, like wt-alphaSyn, exhibit a predominant structure of
      random coil. However, wt-alphaSyn(2SS) adopts an alpha-helical conformation,
      whereas A30P-alphaSyn(2SS) and A53T-alphaSyn(2SS) take on significant beta-sheet
      structure. (c) A30P-alphaSyn(2SS) shows a stronger tendency to aggregate than
      A53T-alphaSyn(2SS) and wt-alphaSyn(2SS). (d) Three isolated isomers of wt
      alphaSyn(2SS) exhibit a propensity for forming oligomers different yet enhanced
      versus that for wt-alphaSyn. These data together substantiate the notion that
      under physiological conditions, human alphaSyn exists as diverse conformational
      isomers which exhibit distinct propensities for aggregation and fibril formation.

PMID- 17209572
TI  - Cationic surfactant changes the morphology of DNA molecules.
AB  - The effect of cetyltrimethylammonium bromide (CTAB), a cationic surfactant, was
      investigated on the aggregated form of DNA molecules in water at a given
      temperature. CTAB caused changes in the aggregated form of DNA molecules from
      loosely packed spherical to rodlike through toroidal one with increasing
      concentration below the critical micelle concentration (CMC). The change was
      suggested to arise from the ion complex formation between CTAB and DNA molecules
      due to the electrostatic interaction, thereby reducing the surface charge and
      solubility in water of the latter.

PMID- 17209571
TI  - Carboxyl terminus of hsc70-interacting protein (CHIP) can remodel mature aryl
      hydrocarbon receptor (AhR) complexes and mediate ubiquitination of both the AhR
      and the 90 kDa heat-shock protein (hsp90) in vitro.
AB  - The regulation of the aryl hydrocarbon receptor (AhR) protein levels has been an
      area of keen interest, given its important role in mediating the cellular
      adaptation and toxic response to several environmental pollutants. The carboxyl
      terminus of hsc70-interacting protein (CHIP) ubiquitin ligase was previously
      associated with the regulation of the aryl hydrocarbon receptor, although the
      mechanisms were not directly demonstrated. In this study, we established that
      CHIP could associate with the AhR at cellular levels of these two proteins,
      suggesting a potential role for CHIP in the regulation of the AhR complex. The
      analysis of the sucrose-gradient-fractionated in vitro translated AhR complexes
      revealed that CHIP can mediate hsp90 ubiquitination while cooperating with
      unidentified factors to promote the ubiquitination of mature unliganded AhR
      complexes. In addition, the immunophilin-like protein XAP2 was able to partially
      protect the AhR from CHIP-mediated ubiquitination in vitro. This protection
      required the direct interaction of the XAP2 with the AhR complex. Surprisingly,
      CHIP silencing in Hepa-1c1c7 cells by siRNA methods did not reveal the function
      of CHIP in the AhR complex, because it did not affect well-characterized
      activities of the AhR nor affect its steady-state protein levels. However, the
      presence of potential compensatory mechanisms may be confounding this particular
      observation. Our results suggest a model where the E3 ubiquitin ligase CHIP
      cooperates with other ubiquitination factors to remodel native AhR-hsp90
      complexes and where co-chaperones such as the XAP2 may affect the ability of CHIP
      to target AhR complexes for ubiquitination.

PMID- 17209573
TI  - Manipulation of cell-sized phospholipid-coated microdroplets and their use as
      biochemical microreactors.
AB  - Cell-sized water droplets coated by a phospholipid layer mimicking the inner
      surface of living cells were manipulated by laser tweezers and used as
      biochemical microreactors. The cell-sized phospholipid-coated microdroplets
      (CPMDs) consisted of a water droplet in mineral oil with a diameter of 1-100
      microm and coated by 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine. We monitored
      the time development of biochemical reactions in a single CPMD obtained after the
      controlled fusion of two CPMDs containing a substrate and an enzyme,
      respectively. We present results on two enzymatic reactions: calcein production
      in the presence of esterase and green fluorescence protein expression.

PMID- 17209574
TI  - Structure of low-density nanoporous dielectrics revealed by low-vacuum electron
      microscopy and small-angle X-ray scattering.
AB  - Aerogels (AGs) are ultralow-density nanoporous solids that have numerous
      potential applications. However, as most AGs are strong insulators with poor
      mechanical properties, direct studies of the complex nanoporous structure of AGs
      by methods such as atomic force and conventional scanning electron microscopy
      (SEM) have not proven feasible. Here, we use low-vacuum SEM to image directly the
      ligament and pore size and shape distributions of representative AGs over a wide
      range of length scales (approximately 100-105 nm). The structural information
      obtained is used for unambiguous, real-space interpretation of small-angle X-ray
      scattering curves for these complex nanoporous systems. Low-vacuum SEM permits
      imaging of both cross-sections and skin layers of AG monoliths. Images of skin
      layers reveal the presence of microcracks, which alter the properties of cast
      monolithic AGs.

PMID- 17209576
TI  - Synthesis of amphiphilic silver nanoparticles in nanoreactors from invertible
      polyester.
AB  - A silver complex is transformed into amphiphilic nanoparticles at room
      temperature using nanoreactors formed from an amphiphilic polyester. It takes a
      few minutes to form silver nanocolloids with a narrow particle size distribution.
      Developed silver forms a stable dispersion in both polar and nonpolar media. The
      amphiphilic polyester acts as a reducing and stabilizing agent simultaneously.
      The size of the synthesized amphiphilic silver nanoparticles depends on the
      concentration of the invertible polyester and solvent polarity.

PMID- 17209575
TI  - Visualization of flow-aligned type I collagen self-assembly in tunable pH
      gradients.
AB  - Collagen is a major component of the extracellular matrix that exhibits unique
      hierarchical organization at multiple length scales ranging from nano to
      macroscale. Despite numerous methods to create collagen-based biomaterials, the
      self-assembly process of collagen ex vivo is poorly understood. Here, we describe
      a system that uses a microfluidic method to investigate the dynamics of collagen
      self-assembly. A main inlet stream of semidilute soluble collagen-I is
      hydrodynamically focused by two side inlet streams, which gradually increases the
      pH in the main stream. This enables dynamic nonequilibrium investigation of the
      self-assembly process simultaneously at different positions and therefore
      different stages in the assembly process within the same system. The device is
      designed for in situ monitoring and characterization of collagen assembly using
      polarization microscopy and X-ray diffraction: the continuous extensional flow
      provides highly ordered phases of the macromolecules over a large distance in the
      outlet microchannel and allows for data collection without material damage. We
      further demonstrate that finite element method simulations provide a good
      description of our experimental results regarding the diffusive phenomena, flow
      profile, and pH distribution. Our approach has broad impact, since it provides a
      powerful means of controlling and investigating the dynamic self-assembly process
      of biomacromolecules.

PMID- 17209577
TI  - Diazonium-functionalized horseradish peroxidase immobilized via addressable
      electrodeposition: direct electron transfer and electrochemical detection.
AB  - A simple one-step procedure is introduced for the preparation of diazonium-enzyme
      adducts. The direct electrically addressable deposition of diazonium-modified
      enzymes is examined for electrochemical sensor applications. The deposition of
      diazonium-horseradish peroxidase leads to the direct electron transfer between
      the enzyme and electrode exhibiting a heterogeneous rate constant, ks, of 10.3 +/
      0.7 s-1 and a DeltaEp of 8 mV (v = 150 mV/s). The large ks and low DeltaEp are
      attributed to the intimate contact between enzyme and electrode attached by one
      to three phenyl molecules. Such an electrode shows high nonmediated catalytic
      activity toward H2O2 reduction. Future generations of arrayed electrochemical
      sensors and studies of direct electron transfer of enzymes can benefit from
      protein electrodes prepared by this method.

PMID- 17209578
TI  - Supported lipid bilayer self-spreading on a nanostructured silicon surface.
AB  - We report on the self-spreading behavior of a supported lipid bilayer (SLB) on a
      silicon surface with various 100 nm nanostructures. SLBs have been successfully
      grown from a small spot of a lipid molecule source both on a flat surface and
      uneven surfaces with 100 nm up-and-down nanostructures. After an hour, the self
      spreading SLB forms a large circle or an ellipse depending on the nanostructure
      pattern. The results are explained by a model that shows that a single-layer SLB
      grows along the nanostructured surfaces. The model is further supported by a
      quantitative analyses of our data. We also discuss the stability of the SLB on
      nanostructured surfaces in terms of the balance between its bending and adhesion
      energies.

PMID- 17209579
TI  - Contrasting effects of temperature on the rheology of normal and reverse wormlike
      micelles.
AB  - Wormlike micelles are flexible polymerlike chains formed by the self-assembly of
      amphiphilic molecules either in water ("normal" worms) or in oil ("reverse"
      worms). Normal and reverse worms have both been studied extensively and have
      generally been found to exhibit analogous rheological properties (e.g., Maxwell
      fluidlike behavior). Here, we report a hitherto unexplored difference between
      these two classes of micelles pertaining to the effect of temperature on their
      rheological properties. For normal worms, the plateau modulus remains constant as
      the sample is heated while the relaxation time exponentially decreases. For
      reverse worms, however, both the plateau modulus and the relaxation time decrease
      exponentially upon heating. Consequently, the zero-shear viscosity of reverse
      worms decreases more rapidly with temperature than for normal worms. To explain
      these differences, we propose that increasing the temperature weakens the driving
      force for micellization in reverse worms whereas it only accelerates the dynamics
      of surfactant exchange in normal worms.

PMID- 17209580
TI  - Carboxy-terminated oligo(ethylene glycol)-alkane phosphate: synthesis and self
      assembly on titanium oxide surfaces.
AB  - The surface immobilization of oligo- and poly(ethylene glycol) on solids is a
      widely used approach to prevent the nonspecific adsorption of proteins, bacteria,
      and cells. A novel tri(ethylene glycol) derivative, phosphoric acid-mono(22
      carboxy-12,15,18,21-tetraoxadocosyl) ester, was synthesized with the aim to
      produce self-assembled monolayers (SAMs) on metal/metal oxide surfaces. This
      compound contains two reactive, terminal moieties: the phosphoric acid group as
      anchor to the surface, and the carboxylic group as linker for further attachment
      of molecules such as peptides and proteins to be present at the surface. The
      adsorption on titanium-dioxide-coated substrates was studied quantitatively and
      the resulting SAMs were characterized by angle-dependent X-ray photoelectron
      spectroscopy (XPS) and spectroscopic ellipsometry. XPS data showed that the
      monomolecular layer is attached with the phosphate group to the substrate, but
      not fully ordered. The dry adlayer thickness was determined to be 13.4 A, which
      is less than expected for a densely packed monolayer. Surface concentration
      calculated from ellipsometry data resulted in a grafting density of 2.03
      molecules/nm2.

PMID- 17209581
TI  - Mesoporous nanotubes of iron phosphate: synthesis, characterization, and
      catalytic property.
AB  - Iron phosphate nanotubes with mesoporous walls are solvothermally synthesized
      using sodium dodecyl sulfate (SDS) as a template. With different template
      concentrations, various shapes of nanosized iron phosphates can be obtained. When
      the concentration of SDS is set at the transition regions between the lamellar
      and the hexagonal mesophases, according to its phase diagram, the coassembly of
      iron phosphate precursor and SDS forms a flake-type mesoporous iron phosphate.
      Otherwise, nanoparticles or bulky sheets of iron phosphates are obtained. The
      followed solvothermal treatments on the mesoporous iron phosphate flakes produce
      iron phosphate nanotubes with mesoporous walls. The removal of the surfactant by
      acetate exchange and heat treatment results in the clean mesoporous nanotubes of
      iron phosphate with diameters of 50-400 nm and lengths of several microns. The
      nanotubular and mesoporous iron phosphate possesses a specific surface area of
      232 m2/g and a bimodal distribution of pore sizes, corresponding to the size of
      mesopores in the walls and the diameter of the nanotubes, respectively. The novel
      nanotubular iron phosphate with composite meso-macroporous structure, in favor of
      the diffusion of reactive molecules, has been tested for direct hydroxylation of
      benzene with hydrogen peroxide and has shown better catalytic performance
      compared with the conventional particulate mesoporous iron phosphate.

PMID- 17209582
TI  - Fast preparation of PtRu catalysts supported on carbon nanofibers by the
      microwave-polyol method and their application to fuel cells.
AB  - PtRu alloy nanoparticles (24 +/- 1 wt %, Ru/Pt atomic ratios = 0.91-0.97)
      supported on carbon nanofibers (CNFs) were prepared within a few minutes by using
      a microwave-polyol method. Three types of CNFs with very different surface
      structures, such as platelet, herringbone, and tubular ones, were used as new
      carbon supports. The dependence of particles sizes and electrochemical properties
      on the structures of CNFs was examined. It was found that the methanol fuel cell
      activities of PtRu/CNF catalysts were in the order of platelet > tubular >
      herringbone. The methanol fuel cell activities of PtRu/CNFs measured at 60
      degrees C were 1.7-3.0 times higher than that of a standard PtRu (29 wt %, Ru/Pt
      atomic ratio = 0.92) catalyst loaded on carbon black (Vulcan XC72R) support. The
      best electrocatalytic activity was obtained for the platelet CNF, which is
      characterized by its edge surface and high graphitization degree.

PMID- 17209583
TI  - In situ nanostructure formation of (micro-hydroxo)bis(micro-carboxylato)
      diruthenium units in nafion membrane and its utilization for selective reduction
      of nitrosonium ion in aqueous medium.
AB  - Nanostructured molecular film containing the (micro-hydroxo)bis(micro
      carboxylato) diruthenium(III) units, [RuIII2(micro-OH)(micro-CH3COO)2(HBpz3)2]+
      ({RuIII2(micro-OH)}), was prepared by an in situ conversion of its micro-oxo
      precursor, [RuIII2(micro-O)(micro-CH3COO)2(HBpz3)2] ({RuIII2(micro-O)}), in a
      Nafion membrane matrix, where HBpz3 is hydrotris(1-pyrazolyl)borate. The
      conversion procedure results in fine nanoparticle aggregates of the {RuIII2(micro
      OH)} units in the Nafion membrane (Nf-{RuIII2(micro-OH)}), where an average
      particle size (4.1 +/- 2.3 nm) is close to the Nafion's cluster dimension of
      approximately 4 nm. Chemically modified electrodes by using the Nafion molecular
      membrane films (Nf-{RuIII2(micro-OH)}-MMFEs) were further developed on ITO/glass
      and glassy carbon electrode (GCE) surfaces, and a selective reduction of
      nitrosonium ion (NO+), presumably through reaction of a {RuIIRuIII(micro-OH)}
      mixed-valence state with HNO2, was demonstrated without interference by molecular
      oxygen in an acidic aqueous solution. The Nf-{RuIII2(micro-OH)}-MMFEs are stable
      even in a physiological condition (pH 7), where the naked {RuIII2(-OH)} complex
      is readily transformed into its deprotonated {RuIII2(micro-O)} form,
      demonstrating an unusual stabilizing effects for the {RuIII2(micro-OH)} unit by
      the Nafion cluster environment.

PMID- 17209584
TI  - Temperature-responsive semipermeable capsules composed of colloidal microgel
      spheres.
AB  - We present semipermeable, hollow capsules (colloidosomes) that expand and
      contract upon heating and cooling. The capsules are composed of micrometer-sized
      poly(N-isopropylacrylamide)-co-acrylic acid microgel particles, which exhibit a
      reversible size transition near 34 degrees C. The microgel particles assemble on
      the surfaces of water droplets in oil. Addition of the diblock copolymer
      poly(butadiene-b-N-methyl 4-vinyl pyridinium iodide) to the oil results in soft,
      elastic membranes of microgel particles that remain intact after the droplet
      interfaces are dissolved. Under heating, the capsules contract reversibly by 13%
      or irreversibly by 40% in radius. These stimulus-responsive colloidosomes might
      be useful for controlled release or as microscopic actuators.

PMID- 17209585
TI  - Synthesis and characterization of large surface hexagonal polyoxometalate
      platelets.
AB  - The polyoxometalates, or POMs (clusters comprising at least two metal and many
      oxygen atoms), have recently gained significant interest, owing to their
      versatile architecture and especially catalytic activities. Due to their high
      catalytic activity but low surface area, there is always a demand for making high
      surface-area POMs, particularly high-surface-area Keggins. Our present work
      demonstrates the 'gluing' of the anionic phosphomolybdate Keggin on gibbsite
      nanoplatelets with a residual positive charge to form large-surface-area
      composites. The resulting composite reported here has been characterized using
      TEM imaging, EDX/TEM (elemental) analysis, FTIR spectroscopy, potentiometric
      titrations, electrophoretic mobility determination, and XRD. The composite
      reported here could be useful in catalysis.

PMID- 17209586
TI  - Many protic ionic liquids mediate hydrocarbon-solvent interactions and promote
      amphiphile self-assembly.
AB  - A large number of protic ionic liquids (PILs) have been found to mediate solvent
      hydrocarbon interactions and promote amphiphile self-assembly. Hexagonal, cubic,
      and lamellar lyotropic liquid crystalline phases were observed in PIL
      hexadecyltrimethylammonium bromide systems. The driving force for the formation
      of the self-assembled aggregate structures has been attributed to an entropic
      contribution to the free energy of association, analogous to the hydrophobic
      effect in water. The specific aggregate structures formed depend upon the
      cationic and anionic components of the PIL and their interactions with the
      amphiphiles.

PMID- 17209588
TI  - Surface ATRP of hydrophilic monomers from ultrafine aqueous silica sols using
      anionic polyelectrolytic macroinitiators.
AB  - A convenient two-step route was developed to prepare new anionic ATRP
      macroinitiators from near-monodisperse poly(2-hydroxyethyl methacrylate)
      precursors by partial esterification with 2-bromoisobutyryl bromide, followed by
      esterification of the remaining hydroxyl groups using excess 2-sulfobenzoic acid
      cyclic anhydride. These new macroinitiators can be electrostatically adsorbed
      onto ultrafine cationic Ludox CL silica sols; subsequent surface polymerization
      of various hydrophilic monomers in aqueous solution at room temperature afforded
      a range of polymer-grafted ultrafine silica sols. The resulting sterically
      stabilized particles were characterized by dynamic light scattering, transmission
      electron microscopy, aqueous electrophoresis, FTIR spectroscopy, and elemental
      microanalyses.

PMID- 17209587
TI  - Cholesterol-phospholipid complexation in fluid bilayers as evidenced by nearest
      neighbor recognition measurements.
AB  - Nearest-neighbor recognition experiments have been carried out using varying
      ratios of exchangeable dimer analogs of 1,2-dimyristoyl-sn-glycero-3
      phosphatidylglycerol and 1,2-distearoyl-sn-glycero-3-phosphatidylglycerol in
      cholesterol-rich unilamellar vesicles at 60 degrees C. Equilibrium dimer
      distributions that were obtained support a structural model of the liquid-ordered
      bilayer in which free cholesterol and the longer-chain phospholipid homodimer are
      in equilibrium with a complex of unique stoichiometry, where one cholesterol
      molecule combines with two of the long-chain phospholipid homodimers. In this
      model, the mixing of the short-chain phospholipids with the uncomplexed long
      chain phospholipids is ideal, and the complexed dimers are shielded from the
      disulfide exchange reaction.

PMID- 17209589
TI  - Do amphiphile aggregate morphologies and interfacial compositions depend
      primarily on interfacial hydration and ion-specific interactions? The evidence
      from chemical trapping.
AB  - Surface-active amphiphiles aggregate spontaneously in water to form association
      colloids such as micelles, microemulsions, and vesicles. The hydrophobic effect
      drives aggregation, but the opposing forces that provide balance and determine
      equilibrium morphologies are not understood, in particular, how specific ion
      effects, which often follow a Hofmeister series, affect the properties of
      association colloids. We have harnessed the competitive trapping of
      arenediazonium ions by weakly basic nucleophiles such as halide counterions,
      anionic headgroups, alcohols, urea, and water, to estimate their concentrations
      in the interfacial regions of association colloids from reaction product yields.
      In the chemical trapping method, product yields are proportional to the
      concentrations of water and other nucleophiles within the interfacial region, not
      their stoichiometric concentrations in solution. Changes in the balance of forces
      controlling aggregate structure are reflected in changes in interfacial
      concentrations of water and other components in association colloids as reported
      by the chemical trapping method. Significant changes in interfacial water and
      counterion concentrations are observed during structural transitions. Specific
      ion effects on sphere-to-rod transitions of cationic amphiphiles are interpreted
      in terms of the strengths of headgroup and counterion pairing and ion hydration
      interactions. Trapping results also provide important information on interfacial
      compositions of microemulsions, vesicles, nonionic micelles and macroemulsions,
      reverse micelles, micelles in aqueous urea, and anionic polyelectrolytes.
      Identifying relationships between aggregate morphology and interfacial
      composition by chemical trapping has just begun.

PMID- 17209590
TI  - Understanding chiral molecular micellar separations using steady-state
      fluorescence anisotropy, capillary electrophoresis, and NMR.
AB  - Chiral separations employing four diastereomers of poly sodium N-undecanoyl
      leucylvalinate (p-SULV) as chiral selectors are probed by use of MEKC, steady
      state fluorescence anisotropy, and NMR. By employing diastereomers and thus
      altering the stereochemistry of a single amino acid in a systematic way, one may
      control the enantiorecognition ability of the chiral selector. As a result, one
      can gain a better understanding of the mechanisms of chiral recognition for the
      two classes of neutral or anionic chiral analytes studied. Evaluation of the
      chiral interactions leading to chiral separations confirmed our earlier
      observation of a strong relationship between the selectivity (alpha) observed
      using a chromatographic separation technique (MEKC) and that determined from the
      spectroscopic parameter, beta. A linear alpha versus beta relationship was
      observed for the molecular micelle p-(L)-SULV with all eight analytes included in
      this study. However, as we earlier predicted, different groups of analytes had
      different slopes, i.e., values of m, suggesting different chiral separation
      mechanisms. Evaluation of the data allowed a grouping of the analytes according
      to the primary site of chiral interaction with the leucine or valine moiety of
      molecular micelle chiral headgroup.

PMID- 17209591
TI  - Premicellar accelerated decarboxylation of 6-nitrobenzisoxazole-3-carboxylate ion
      and its 5-tetradecyloxy derivative.
AB  - Didodecyldialkylammonium chloride and bromide (alkyl = Me, Et, n-Pr, n-Bu)
      accelerate the spontaneous decarboxylation of 6-nitrobenzisoxazole-3-carboxylate
      ion, 1,H, and its 5-tetradecyloxy derivative, 1,OTD. With most of these
      surfactants, first-order rate constants, kobs, go through maxima in very dilute
      surfactant and then decrease and go through minima as association colloids form.
      These phenomena are not explicable in terms of substrate-induced micellization.
      However, kobs increases in the N-alkyl sequence Me < Et < n-Pr < n-Bu, as is
      typical of decarboxylations in association colloids of single-chain surfactants.
      Reaction in premicelles is accelerated by an initial increase in 1,H. The factors
      that control relative rates of spontaneous reactions in premicelles and in the
      association colloids, in particular, depletion of water at the reaction center
      and association of substrate and quaternary ammonium centers, are discussed with
      respect to the roles of substrate and surfactant hydrophobicities.

PMID- 17209592
TI  - Formation of dense self-assembled monolayers of (n-decyl)trichlorosilanes on
      Ta/Ta2O5.
AB  - Tantalum pentoxide (Ta2O5) is a promising material for the realization of
      biological interfaces because of its high dielectric constant, its high chemical
      stability, and its excellent passivating properties. Nevertheless, the deposition
      of highly organized silane SAMs to realize well-defined and tailored Ta2O5-based
      (bio)interfaces, has not been studied in great detail as of yet. In this work, we
      have investigated the formation of a highly ordered, dense monolayer of
      trichlorosilanes on Ta2O5 surfaces. Specifically, two different cleaning
      procedures for Ta2O5 were compared and (n-decyl)trichlorosilane (DTS) was used to
      study the effect of both cleaning methods on the silanization of Ta2O5. Both
      types of cleaning allowed the formation of complete and crystalline DTS
      monolayers on Ta2O5, in contrast with the incomplete, disordered silane layer
      assembled on uncleaned Ta2O5. The deposited self-assembled monolayers were
      studied by means of contact angle goniometry, Brewster angle FTIR, X-ray
      photoelectron spectroscopy, cyclic voltammetry, and ellipsometry. Infrared
      analysis exhibited a highly ordered DTS silane film on Ta2O5 and indicated a
      larger tilt angle of the alkyl chains on this substrate by comparison to DTS on
      SiO2. Furthermore, with use of ellipsometry and XPS, the silane film thickness on
      Ta2O5 was determined to be substantially smaller than that reported in the
      literature for DTS on SiO2, supporting the observations of an increased tilt
      angle (approximately 45 degrees ) on Ta2O5 than on SiO2 (approximately 10 degrees
      ). By means of cyclic voltammetry, the formation of a dense, essentially pinhole
      free, silane film was observed on the cleaned samples. In conclusion, the fully
      characterized and optimized procedure for the silanization of Ta2O5 surfaces with
      trichlorosilanes will allow the formation of well-defined, reproducible, and
      controllable chemical interfaces on Ta2O5.

PMID- 17209593
TI  - Ion distribution around electrostatically stabilized polystyrene latex particles
      studied by ellipsometric light scattering.
AB  - The ion distribution around electrostatically stabilized polystyrene latex
      spheres for different ionic strengths is investigated by ellipsometric light
      scattering. This method is sensitive to the refractive index profile around
      colloidal particles, which is affected by the local salt content. At an average
      salt concentration of c* = 10(-4) mol L(-1), the ion concentration at the
      particle interface increases discontinuously, and a layer of high salt content
      with 20-30 nm thickness is built up. The observation cannot be explained within
      the framework of the Poisson-Boltzmann equation; it rather resembles a prewetting
      transition. Interactions that could possibly lead to a stabilization of the
      observed layer of high salt content are discussed.

PMID- 17209594
TI  - Rupturing polymeric micelles with cyclodextrins.
AB  - Small-angle neutron scattering has been used to investigate the associative
      structures formed by triblock copolymers of poly(ethylene oxide) (PEO)
      polypropylene oxide (PPO)-poly(ethylene oxide) (PEO) (also known as Pluronics)
      and to monitor the structural changes occurring upon complexation with
      heptakis(2,6-di-O-methyl)-beta-cyclodextrin (hbeta-CD) over the temperature range
      from 5 to 70 degrees C. At low temperature, the Pluronics are dispersed as
      unimers. Close to ambient temperature, the hydrophobicity of PPO causes the
      aggregation of the polymers into spherical micelles with core sizes between 40
      and 50 A and a high inclusion of solvent. The aggregation number increases with
      temperature as the hydrophobicity of the core is gradually enhanced. hbeta-CD
      spontaneously forms pseudopolyrotaxanes with the triblock copolymers either when
      in their unimer form or micellized. The complexation results in an increase in
      the effective critical micellar concentration. It is suggested that the
      cyclodextrins thread onto the polymer backbone to localize preferentially on the
      central PPO block, therefore improving its water solubility. At temperatures
      where the polymers exist in micellar form, complexation with hbeta-CD gives rise
      to a complete disruption of the aggregates. These processes are highly
      temperature-dependent. Above 50 degrees C, the break-up of the aggregates is
      inhibited, and large-scale aggregation is observed.

PMID- 17209595
TI  - Lateral phase separation gives multiple lamellar phases in a "binary"
      surfactant/water system: the phase behavior of sodium alkyl benzene
      sulfonate/water mixtures.
AB  - We have examined the structure of the lamellar phase (Lalpha) that coexists with
      a micellar solution (L1) for a commercial sodium alkyl benzene sulfonate (LAS)
      mixed with water. The surfactant is a mixture containing C10-C13 alkyl chains,
      having all positional isomers of the benzene sulfonate group present except the 1
      isomer. Unusually for ionic surfactants, the difference in compositions between
      the coexisting L1 and Lalpha phases is large (L1 = approximately 20 wt % LAS;
      Lalpha = approximately 65 wt %). The main technique employed was X-ray
      diffraction, supplemented by optical microscopy and differential scanning
      calorimetry (DSC). At ambient temperatures, the lamellar phase gives a single
      diffraction pattern with the main reflection (d) at approximately 32.5 A,
      whatever the composition. However, above 40 degrees C, the diffraction peak
      becomes broader and moves to higher d values. At higher temperatures still,
      several distinct and different diffraction peaks are observed, differing in
      detail according to composition. The largest d values (approximately 42-4 A) are
      observed for the lowest LAS concentrations, while the largest number of separate
      reflections (five) occurs for samples with approximately 44-50% LAS, both at the
      highest temperatures. Although there are some differences in the data between
      heating and cooling cycles, the d values return to the original value at low
      temperature. There are no observable transitions in DSC, nor is there any
      heterogeneity in the lamellar phase observable by microscopy. The data clearly
      indicate that there is some lateral separation of the different LAS isomers
      within the bilayers, which results in the formation of local lamellar regions
      having different surfactant compositions. This lateral phase separation may arise
      from the presence of an (electrostatic) attractive interaction, which gives rise
      to an upper consolute loop within the lamellar phase region of a pure LAS isomer.
      Similar mechanisms may occur in biological membranes and could be responsible for
      the occurrence of membrane lipid patches.

PMID- 17209596
TI  - Steric interactions between physically adsorbed polymer-coated colloidal
      particles: soft or hard?
AB  - The steric interaction potential between colloidal particles imparted by adsorbed
      polymer layers is directly related to their structure. Due to the complexity of
      these interfacial structures, the steric potential may behave differently at
      different interparticle separations. In this study, we proposed a combined model
      of the equivalent hard-sphere model (EHS) and the Hayter-Penfold/Yukawa model
      (HPY) to describe the steric potential due to adsorbed homopolymers on colloidal
      particles. The EHS potential describes the dense train/small-loop region and the
      HPY potential the more diffuse tail/long-loop region. The steric potential was
      extracted from the structure factors measured by small-angle neutron scattering
      (SANS). It was found that this combined model gave better agreement with
      experimental data than either of its component models alone. This study also
      shows that the adsorbed polymer layer in a good solvent partially collapses when
      the layers approach one another, which is also supported by an NMR solvent
      relaxation study.

PMID- 17209597
TI  - Self-organization of a wedge-shaped surfactant in monolayers and multilayers.
AB  - The self-organization behavior of a wedge-shaped surfactant, disodium-3,4,5
      tris(dodecyloxy)phenylmethylphosphonate, was studied in Langmuir monolayers (at
      the air-water interface), Langmuir-Blodgett (LB) monolayers and multilayers, and
      films adsorbed spontaneously from isooctane solution onto a mica substrate (self
      assembled films). This compound forms an inverted hexagonal lyotropic liquid
      crystal phase in the bulk and in thick adsorbed films. Surface pressure isotherm
      and Brewster angle microscope (BAM) studies of Langmuir monolayers revealed three
      phases: gas (G), liquid expanded (LE), and liquid condensed (LC). The surface
      pressure-temperature phase diagram was determined in detail; a triple point was
      found at approximately 10 degrees C. Atomic force microscope (AFM) images of LB
      monolayers transferred from various regions of the phase diagram were consistent
      with the BAM images and indicated that the LE regions are approximately 0.5 nm
      thinner than the LC regions. AFM images were also obtained of self-assembled
      films after various adsorption times. For short adsorption times, when monolayer
      self-assembly was incomplete, the film topography indicated the coexistence of
      two distinct monolayer phases. The height difference between these two phases was
      again 0.5 nm, suggesting a correspondence with the LE/LC coexistence observed in
      the Langmuir monolayers. For longer immersion times, adsorbed multilayers
      assembled into highly organized periodic arrays of inverse cylindrical micelles.
      Similar periodic structures, with the same repeat distance of 4.5 nm, were also
      observed in three-layer LB films. However, the regions of organized periodic
      structure were much smaller and more poorly correlated in the LB multilayers than
      in the films adsorbed from solution. Collectively, these observations indicate a
      high degree of similarity between the molecular organization in Langmuir
      layers/LB films and adsorbed self-assembled films. In both cases, monolayers
      progress through an LE phase, into LE/LC coexistence, and finally into LC phase
      as surface density increases. Following the deposition of an additional bilayer,
      the film reorganizes to form an array of inverted cylindrical micelles.

PMID- 17209598
TI  - pH-controlled, polymer-mediated assembly of polymer micelle nanoparticles.
AB  - We describe pH-controlled, polymer-mediated assembly of polymer micelles in
      aqueous media based on reversible complexation between the micelles of pyrene
      labeled poly(epsilon-caprolactone)-b-poly(carboxylic acid) copolymers and proton
      accepting water-soluble polymers such as poly(ethylene glycol) (PEG), poly(2
      ethyl-2-oxazoline) (PEtOz), and poly(1-vinylpyrrolidone) (PVP). The key factor
      determining assembly phenomena was identified as the modulation of hydrogen
      bonding interaction between ionizable anionic micellar shells and the proton
      accepting polymers by the pH control. As pH decreased from 7.4 to 2.0, the
      mixture of the polymer micelles and polymers underwent assembly and formed solid
      hybrids at specific pH values. The micelles assembled in the hybrid could be
      reversibly dispersed as micelles above specific pH ranges. The
      assembly/disassembly behavior as well as phase transitions of the micelle/proton
      accepting polymer could be precisely controlled by adjusting pH. This assembling
      behavior depended on the rationally designed parameters such as the chemical
      structure and length of micellar shell-forming poly(carboxylic acid)s and the
      class of proton-accepting polymers.

PMID- 17209599
TI  - Liquid crystalline phases and their dispersions in aqueous mixtures of glycerol
      monooleate and glyceryl monooleyl ether.
AB  - The aqueous phase behavior of mixtures of 1-glycerol monooleate (GMO) and its
      ether analogue, 1-glyceryl monooleyl ether (GME) has been investigated by a
      combination of polarized microscopy, X-ray diffraction, and NMR techniques. Three
      phase diagrams of the ternary GMO/GME/water system have been constructed at 25,
      40, and 55 degrees C. The results demonstrate that the increasing amount of GME
      favors the formation of the reversed phases, evidenced by the transformation of
      the lamellar and bicontinuous cubic liquid crystalline phases of the binary
      GMO/water system into reversed micellar or reversed hexagonal phases. For a
      particular liquid crystalline phase, increasing the GME content has no effect on
      the structural characteristics and hydration properties, thus suggesting ideal
      mixing with GMO. Investigations of dispersed nanoparticle samples using shear and
      a polymeric stabilizer, Pluronic F127, show the possibility of forming two
      different kinds of bicontinuous cubic phase nanoparticles by simply changing the
      GMO/GME ratio. Also NMR self-diffusion measurements confirm that the block
      copolymer, Pluronic F127, used to facilitate dispersion formation, is associated
      with nanoparticles and provides steric stabilization.

PMID- 17209600
TI  - An effective way to stabilize colloidal particles dispersed in polar and nonpolar
      media.
AB  - This article offers a new approach to building up self-adjustable invertible
      polymer coatings at solid surfaces. The approach is based on a two-step process.
      In the first step, the surface of dispersed TiO2 has been functionalized with the
      aid of toluene diisocyanate (TDI) as a coupling agent. In the second step, the
      chains of amphiphilic oligoester have been covalently grafted to the titanium
      dioxide surface functionalized with isocyanate groups. It is shown that the
      titania modified in this way can form stable suspensions in both polar (water)
      and nonpolar (toluene) media. Multiple redispersion cycles show the ability of
      the modified titanium dioxide particles, after their removal from one type of
      dispersion and consequent drying, to be redispersed in dispersing media strongly
      differing by polarity from the previous.

PMID- 17209601
TI  - Gold film surface preparation for self-assembled monolayer studies.
AB  - Evaporated gold films are frequently used as substrates for the study of
      biomolecular adsorbates, nanoparticle systems, amd partial and full monolayer
      films. These studies often benefit from a predeposition cleaning of the surface
      that removes adventitiously adsorbed material from laboratory contaminants.
      Scanning tunneling microscopy (STM) is used in this study to explore the
      microscopic consequences of two pretreatment protocols used in literature reports
      of self-assembled monolayers, based on sulfochromic and piranha acid solutions.
      These measurements show that treatment of the Au/mica surface with piranha acid
      can lead to extensive and uncontrolled etching of the surface and severe
      disruption of the surface topography; extended exposure causes the precipitation
      of crystallites on the surface that are highly mobile during STM imaging
      processes. Exposure of Au/mica surfaces to sulfochromic acid leads to the
      formation of permanent etch pits of the surface that are exclusively one Au layer
      deep; extended exposure leads to progressive etching and oxidation of the
      surface, ultimately leading to the formation of 0.33-0.36 nm high islands on the
      otherwise flat Au/mica surface. The piranha acid solutions are significantly more
      likely to cause the Au film to delaminate from the mica support than are the
      sulfochromic acid solutions. These results show that sulfochromic surface
      preparation is a direct and reliable method for the elimination of organic
      residues from Au(111)-textured surfaces, while causing a minimum of structural
      and chemical surface damage.

PMID- 17209602
TI  - Effect of capillary condensation on friction force and adhesion.
AB  - Friction force measurements have been conducted with a colloid probe on mica and
      silica (both hydrophilic and hydrophobized) after long (24 h) exposure to high
      humidity air. Adhesion and friction measurements have also been performed on
      cellulose substrates. The long exposure to high humidity led to a large
      hysteresis between loading and unloading in the friction measurements with
      separation occurring at large negative applied loads. The large hysteresis in the
      friction-load relationship is attributed to a contact area hysteresis of the
      capillary condensate which built up during loading and did not evaporate during
      the unloading regime. The magnitude of the friction force varied dramatically
      between substrates and was lowest on the mica substrate and highest on the
      hydrophilic silica substrate, with the hydrophobized silica and cellulose being
      intermediate. The adhesion due to capillary forces on cellulose was small
      compared to that on the other substrates, due to the greater roughness of these
      surfaces.

PMID- 17209603
TI  - Comparative studies on electrogenerated chemiluminescence of luminol on gold
      nanoparticle modified electrodes.
AB  - Comparative studies on the electrogenerated chemiluminescence (ECL) behavior of
      luminol on various electrodes modified with gold nanoparticles of different size
      were carried out in neutral solution by conventional cyclic voltammetry (CV). The
      results demonstrated that the gold nanoparticle modified electrodes could
      generate strong luminol ECL in neutral pH conditions. The catalytic performance
      of gold nanoparticle modified electrodes on luminol ECL depended not only on the
      gold nanoparticles but also on the substrate. Gold electrode and glassy carbon
      electrode were the most suitable substrates for the self-assembly of gold
      nanoparticles. Moreover, the gold nanoparticle modified gold and glassy carbon
      electrode had satisfying stability and reproducibility and did not need tedious
      pretreatment of electrode surface before each measurement. It was also found that
      luminol ECL behavior depended on the size of gold nanoparticles. The most intense
      ECL signals were obtained on a 16-nm-diameter gold nanoparticle modified
      electrode. The modified electrode prepared by the self-assembly method exhibited
      much better catalytic effect on luminol ECL than that prepared by the
      electrically deposited method. The ECL behavior of luminol on a gold nanoparticle
      self-assembled gold electrode was also investigated by other transient-state
      electrochemical techniques, such as chronoamperometry, differential pulse
      voltammetry, normal pulse voltammetry, and square wave voltammetry. The strongest
      ECL intensity was obtained under square wave voltammetric condition.

PMID- 17209604
TI  - A computational study of the reconstruction of amorphous mesoporous materials
      from gas adsorption isotherms and structure factors via evolutionary
      optimization.
AB  - A general method for the three-dimensional reconstruction of mesoporous materials
      by evolutionary optimization against target data is developed. The method is
      applied specifically in reconstruction of amorphous material models using gas
      adsorption data, structure factor data, or a combination of both. A recently
      introduced lattice-gas approach is used to model adsorption in these
      calculations, and a high-pass limited Fourier representation is used to
      facilitate evolution of large-scale structures during the optimization.
      Reconstructions are made of several material models which mimic real materials
      obtained either by phase separation and etching or by sol-gel processing.
      Analysis of the reconstructions provides considerable insight into the type and
      quantity of structural information probed by gas adsorption and small-angle
      scattering experiments. We find that reconstructions based only on structure
      factors tend to underestimate the mean pore size. We also find that in many cases
      excellent reconstructions can be obtained using only adsorption-branch data, and
      that in all cases reconstructions based jointly on both types of data are
      superior to those based only on one, suggesting that these measures contain
      "complementary" information. It is also found that in most cases the use of
      desorption data is not warranted, and that the use of adsorption data taken at
      many temperatures will not improve reconstructions. The reproducibility of the
      method is shown to be satisfactory. The method can be computationally expensive
      if gas adsorption data are used, but it is easily parallelized, and therefore
      results can still be obtained in reasonable time. Finally, the possible
      application of this approach to real systems, including templated porous
      materials, is discussed.

PMID- 17209605
TI  - Charge-transfer complex study by chemical force spectroscopy: a dynamic force
      spectroscopic approach.
AB  - Charge-transfer interaction, as a reversible and rapid phenomenon, was evidenced
      by force microscopy. Pull-off forces were measured between a tip grafted with a
      trinitrofluorenone derivative and a surface functionalized with an electron-rich
      aromatic anthracene compound in a dodecane environment. The effect of the sweep
      time on the measured interaction forces is described, together with an extensive
      study of a competitive influence of free aromatic molecules in dodecane diluted
      solutions. These forces depend on the nature of the competitor and its
      concentration as well as on the velocity of tip/sample separation.

PMID- 17209606
TI  - Air-facilitated three-phase contact formation at hydrophobic solid surfaces under
      dynamic conditions.
AB  - The paper presents results documenting the mechanism of facilitation of the three
      phase contact (TPC) formation due to gas entrapped during immersion of
      hydrophobic (Teflon) plates into distilled water and n-octanol solutions.
      Collisions, bouncing, the time scale of the TPC formation, and bubble attachment
      to Teflon plates of different surface roughness were studied using a high-speed
      camera. Processes occurring during the microscopic wetting film formation at the
      Teflon plates were monitored using the microinterferometric method (Scheludko
      Exerowa cell). A strong relation between the time necessary to form a stable TPC
      and the roughness of the Teflon was observed. The higher the Teflon roughness was
      the shorter the time for the TPC formation. This effect can be attributed to two
      factors: (i) local differences in the thickness of the thinning intervening
      liquid layer (quicker attainment of rupture thickness at pillars of rough
      surface) and/or (ii) the presence of gas at the hydrophobic surface. Experimental
      findings, that (i) prolongation of the plate immersion time resulted in quicker
      TPC formation, (ii) white irregular and disappearing spots (air pockets) were
      recorded during the wetting film formation, and (iii) high n-octanol
      concentration caused prolongation of the time of the TPC formation, show that
      attachment (TPC formation) of the colliding bubble to hydrophobic surfaces was
      facilitated by air entrapped at the Teflon plates (and re-distributed) during
      their immersion into water phase. Thus, on collision instead of solid/gas wetting
      liquid film a thin gas/liquid/gas foam film was formed which facilitated the TPC
      formation.

PMID- 17209607
TI  - Monomer adsorption on terraces and nanotubes.
AB  - We construct a nonsparse transfer matrix (T-matrix) for a lattice gas model of
      monomers adsorbed on planar and nanotube surfaces of arbitrary geometry. The
      model can accommodate any number of higher-order pairwise adsorbate-adsorbate
      interactions. The technique is sufficiently general for application to
      nonequivalent adsorption sites and coadsorption of two or more monomer species.
      The T-matrices for monomer adsorption on a finite width terrace and for monomer
      adsorption on a nanotube, both of the same lattice geometry, share a basic G
      matrix. First, the G-matrix is diagrammatically and recursively constructed.
      Then, its elements are modified to provide the T-matrix elements for either the
      terrace or the nanotube. The T-matrices for several particular lattice geometries
      previously studied as special cases are easily recovered with the generalized
      technique presented here. This generalization also provides a vectorized
      algorithm for efficient use on multi-parallel processors and supercomputers.

PMID- 17209608
TI  - Blends of poly(epsilon-caprolactone) and intermediate molar mass polystyrene as
      Langmuir films at the air/water interface.
AB  - Poly(epsilon-caprolactone)/polystyrene (PCL/PS) blends, where nonamphiphilic PS
      is glassy in the bulk state at the experimental temperature of 22.5 degrees C,
      are immiscible as Langmuir films at the air/water (A/W) interface. Surface
      pressure-area per monomer isotherm analyses indicate that the surface
      concentration of amphiphilic PCL is the only factor influencing the surface
      pressure below the collapse transition. For PS-rich blends, Brewster angle
      microscopy (BAM) studies at the A/W interface and atomic force microscopy studies
      on Langmuir-Schaefer films reveal that PS nanoparticle aggregates formed at very
      low surface pressures can form networks upon further compression. The
      morphologies seen in PS-rich blends (networklike rings) are consistent with a
      recent study of a nonamphiphilic polyhedral oligomeric silsesquioxane (POSS),
      octaisobutyl-POSS, blended with amphiphilic poly(dimethylsiloxane), suggesting
      that the nonamphiphilic PS aggregates at the A/W interface produce domains with
      dipole densities that differ from that of pure PCL. In all composition regimes,
      the amphiphilic PCL phase tends to spread and form a continuous surface layer at
      the A/W interface, while simultaneously improving the dispersion of
      nonamphiphilic PS domains. During film expansion, BAM images show a gradual
      change in the surface morphology from highly continuous networklike structures
      (PS-rich blends) to broken ringlike structures (intermediate composition) to
      small discontinuous aggregates (PCL-rich blends). This study provides valuable
      information on the morphological evolution of semicrystalline PCL-based polymer
      blends confined in a "two-dimensional" geometry at the A/W interface and
      fundamental insight into the influence of microstructure (domain size, phase
      separated structures, crystalline morphology, etc.) on the interfacial properties
      of blends as Langmuir films.

PMID- 17209609
TI  - Improvements in the characterization of the crystalline structure of acid
      terminated alkanethiol self-assembled monolayers on Au(111).
AB  - We report a study of acid-terminated self-assembled monolayers of alkanethiols of
      different length, 11-mercaptoundecanoic acid (11-MUA) and 16-mercaptohexadecanoic
      acid (16-MHDA), on Au(111). Scanning tunneling microscopy (STM), X-ray
      photoelectron spectroscopy (XPS), cyclic voltammetry (CV), electrochemical
      impedance spectroscopy (EIS), and contact angle techniques were used for
      characterization, and the results were compared with those obtained from n
      alkanethiols of similar chain length, providing a detailed description of the two
      dimensional crystalline structure. Molecular resolution STM images show that 11
      MUA forms a dense-packed monolayer arranged in a (square root 3 x square root
      3)R30 degrees structure with a c(2 x 4) superlattice, where the simple hexagonal
      phase, the c(2 x 4) superlattice, and nonordered areas coexist. 16-MHDA assembles
      in a uniform monolayer with similar morphology to that of 11-MUA, but molecular
      resolution could not be reached in STM due to both the hydrophilicity of the acid
      groups and the poor conductivity of the thick monolayer. Nevertheless, the
      monolayer thicknesses estimated by XPS and electrochemistry and the highly
      blocking character of the film observed by electrochemistry as well as the low
      water contact angle are consistent with 16-MHDA molecules forming a compact
      monolayer on the Au(111) substrate with fully extended alkyl chains and acid
      groups pointing away from the surface. The results obtained for 16-MHDA were
      reproducible under different preparation conditions such as the addition or
      omission of acetic acid to the ethanolic solution. Contrary to other reports, we
      demonstrate that ordered acid-terminated self-assembled monolayers are obtained
      with the same preparation conditions as those of the methyl-terminated ones,
      without any additional treatment.

PMID- 17209610
TI  - Condensing effect of palmitic acid on DPPC in mixed Langmuir monolayers.
AB  - The interaction between deuterated dipalmitoylphosphatidylcholine (DPPC-d62) and
      palmitic acid (PA) in mixed Langmuir monolayers is studied using vibrational sum
      frequency generation (VSFG) spectroscopy. Palmitic acid is an additive in
      exogenous lung surfactant preparations such as Survanta and Surfaxin. The effect
      of PA on the chain conformation and orientation of DPPC in the liquid-expanded
      and condensed phases is explored. A condensing effect of PA on DPPC is observed
      with VSFG. At 12 mN/m, DPPC-d62 alone is in the liquid-expanded phase. Adding PA
      increases the conformational ordering of DPPC chains and causes DPPC to
      transition from the expanded phase into the condensed phase. At 42 mN/m, DPPC-d62
      and PA form a mixed structure in the condensed phase. The presence of PA
      decreases the chain tilt angle of DPPC, increasing the orientational ordering of
      DPPC chains. At 42 mN/m, there is also evidence from the frequency red shift of
      the PO2- symmetric stretch that the carboxyl group of PA forms a hydrogen bond
      with the phosphate group of DPPC in the condensed phase. From this work the
      effect of PA on DPPC is 2-fold: (1) PA increases the chain ordering of DPPC and
      promotes the LE and TC phase separation and (2) due to the miscibility between
      DPPC and PA in the condensed phase, PA decreases the collapse pressure.

PMID- 17209611
TI  - Density depletion at solid-liquid interfaces: a neutron reflectivity study.
AB  - Neutron reflectivity experiments conducted on self-assembled monolayers (SAMs)
      against polar (water) and nonpolar (organic) liquid phases reveal further
      evidence for a density reduction at hydrophobic-hydrophilic interfaces. The
      density depletion is found at the interface between hydrophobic dodecanethiol
      (C12) and hexadecanethiol (C16) SAMs and water and also between hydrophilic SAMs
      (C12/C11OH) and nonpolar fluids. The results show that the density deficit of a
      fluid in the boundary layer is not unique to aqueous solid-liquid interfaces but
      is more general and correlated with the affinity of the liquid to the solid
      surface. In water the variation of pH has only minor influence, while different
      electrolytes taken from the Hofmeister series seem to increase the depletion. On
      hydrophobic SAMs an increase in density depletion with temperature was observed,
      in agreement with Monte Carlo simulations performed on corresponding model
      systems. The increase in the water density depletion layer is governed by two
      effects: the surface energy difference between water and the substrate and the
      chemical potential of the aqueous phase.

PMID- 17209612
TI  - Structure of anionic phospholipid coatings on silica by dissipative quartz
      crystal microbalance.
AB  - The adsorption of anionic phospholipids on silica was investigated by the
      dissipative quartz crystal microbalance (QCM) technique. Liposomes composed of 1
      mM 80:20 mol % of 1-palmitoyl-2-oleyl-sn-glycero-3-phosphatidylcholine
      (POPC)/phosphatidic acid, POPC/phosphatidylglycerol, or POPC/phosphatidylserine
      in N-(2-hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid) buffer at pH 7.4 (with
      or without 3 mM of CaCl2) were examined. We have previously demonstrated that
      similar phospholipid coatings can be used in capillary electrochromatography as a
      stationary phase for the separation of analytes. In this work, we focus on the
      formation of the coatings and on the type of lipid structure formed on silica.
      The QCM investigation comprised qualitative results based on changes in frequency
      and resistance, and quantitative modeling of the obtained results. The latter was
      performed using the dissipative QCM, which measures the quartz crystal impedance,
      combined with equivalent circuit analysis. A previously developed coating and
      cleaning procedure for phospholipid-coated fused silica capillaries was adopted
      in this study, and the same silica-coated crystal was used throughout the QCM
      study. We will demonstrate in this work that the type of lipid structure formed
      on silica, that is, a rather rigid supported lipid bilayer or a viscoelastic
      supported vesicle layer (SVL), is highly dependent on the lipid and solvent
      composition. We also show for the first time that the modeling of the dissipative
      QCM data can be used to extract a more quantitative picture of an adsorbed SVL,
      because, so far, published studies have merely used the QCM data in a qualitative
      sense.

PMID- 17209613
TI  - Interfacial behavior of a series of amphiphilic block co-dendrimers.
AB  - Amphiphiles with a dendritic structure are attractive materials as they combine
      the features of dendrimers with the self-assembling properties and interfacial
      behavior of amphiphiles. We have designed and synthesized three series of
      segmented amphiphilic block co-dendrimers (Janus-type) and studied their
      interfacial properties on the Langmuir trough. Various behaviors are observed
      with, as a rule, the lowest generation dendrimers behaving more or less like
      traditional amphiphiles while the larger molecules tend to exhibit more
      complicated isotherms, with a non-straightforward temperature dependence, one
      particular molecule seemingly forming supramolecular assemblies spontaneously.
      The results presented here, obtained on a series of molecules where many
      parameters have been varied systematically, show the limits that should be kept
      in mind when designing amphiphilic dendrimers.

PMID- 17209614
TI  - Dynamics of interactions involving deformable drops: hydrodynamic dimpling under
      attractive and repulsive electrical double layer interactions.
AB  - A model developed previously to analyze force measurements between two deformable
      droplets in the atomic force microscope [Langmuir 2005, 21, 2912-2922] is used to
      model the drainage of an aqueous film between a mica plate and a deformable
      mercury drop for both repulsive and attractive electrical double-layer
      interactions between the mica and the mercury. The predictions of the model are
      compared with previously published data [Faraday Discuss. 2003, 123, 193-206] on
      the evolution of the aqueous film whose thickness has been measured with
      subnanometer precision. Excellent agreement is found between theoretical results
      and experimental data. This supports the assumptions made in the model which
      include no-slip boundary conditions at both interfaces. Furthermore, the
      successful fit attests to the utility of the model as a tool to explore details
      of the drainage mechanisms of nanometer-thick films in which fluid flow, surface
      deformations, and colloidal forces are all involved. One interesting result is
      that the model can predict the time at which the aqueous film collapses when
      attractive mica-mercury forces are present without the need to invoke capillary
      waves or other local instabilities of the mercury/electrolyte interface.

PMID- 17209615
TI  - Effects of molecular structure and interfacial ligation on the precision of Cu
      bound alpha,omega-mercaptoalkanoic acid "molecular ruler" stacks.
AB  - Nanolithography processes based on designed, precision thickness multilayer thin
      films (molecular rulers) have been reported that enable patterning of features on
      surfaces from a few to the hundred nanometer range. These strategies are unique
      in their potential ability to enable wafer scale patterning of features of just a
      few nanometers. If these techniques could be developed to be sufficiently precise
      and generally applicable, they would fill a long-standing need in nanoscience. In
      this study a systematic and detailed analysis of the growth mechanisms and
      molecular layer structures has been carried out for the mercaptoalkanoic acid
      copper ion multilayer thin film system currently used as the standard
      nanolithography resist. Our results show these films form via a redox reaction of
      thiol groups with surface-ligated Cu(II) ions to form adlayers at only
      approximately 50% coverage with islanding of the alkyl chains, thereby leading to
      rough topographies and less than theoretical thicknesses based on a 1:1 ideal
      adlayer. Strategies are suggested to help overcome these issues for molecular
      resist applications in nanolithographic processing.

PMID- 17209616
TI  - Two-dimensional polymeric nanomaterials through cross-linking of polybutadiene-b
      poly(ethylene oxide) monolayers at the air/water interface.
AB  - Two-dimensional polymeric nanomaterials consisting of a continuously cross-linked
      polybutadiene (PB) two-dimensional network with poly(ethylene oxide) (PEO)
      domains of controlled sizes trapped within the PB network were synthesized. To
      reach that goal, novel (PB(Si(OEt)3)-b-PEO)3 star block copolymers were designed
      by hydrosilylation of the pendant double bonds of (PB-b-PEO)3 star block
      copolymer precursors with triethoxysilane. The (PB(Si(OEt)3)-b-PEO)3 star block
      copolymers were characterized by 1H NMR and IR spectroscopy. Self-condensation of
      the triethoxysilane pendant groups under acidic conditions led to a successful
      cross-linking of the polybutadiene blocks directly at the air/water interface
      without any additives or reagents. This strategy was found more efficient than
      radical cross-linking of (PB-b-PEO)3 with AIBN to get a homogeneously cross
      linked monolayer of controlled and fixed morphology as demonstrated by the easy
      mechanical removal of the cross-linked Langmuir film from the water surface. As
      shown by AFM imaging, this strategy allows the accurate control of the PEO "pore"
      size depending on the monolayer surface pressure applied during the cross-linking
      reaction. The subphase pH and surface pressure influence on the cross-linking
      kinetics and monolayer morphologies were investigated by Langmuir trough studies
      (isotherm and isobar experiments) and AFM imaging.

PMID- 17209617
TI  - Storage and separation of CO2 and CH4 in silicalite, C168 schwarzite, and IRMOF
      1: a comparative study from Monte Carlo simulation.
AB  - Storage of pure CO2 and CH4 and separation of their binary mixture in three
      different classes of nanostructured adsorbents--silicalite, C168 schwarzite, and
      IRMOF-1--have been compared at room temperature using atomistic simulation. CH4
      is represented as a spherical Lennard-Jones molecule, and CO2 is represented as a
      rigid linear molecule with a quadrupole moment. For pure component adsorption,
      CO2 is preferentially adsorbed than CH4 in all the three adsorbents over the
      pressure range under this study, except in C168 schwarzite at high pressures. The
      simulated adsorption isotherms and isosteric heats match closely with available
      experimental data. A dual-site Langmuir-Freundlich equation is used to fit the
      isotherms satisfactorily. Compared to silicalite and C168 schwarzite, the
      gravimetric adsorption capacity of pure CH4 and CO2 separately in IRMOF-1 is
      substantially larger. This implies that IRMOF-1 might be a potential storage
      medium for CH4 and CO2. For adsorption from an equimolar binary mixture, CO2 is
      preferentially adsorbed in all three adsorbents. Predictions of mixture
      adsorption with the ideal-adsorbed solution theory on the basis of only pure
      component adsorption agree well with simulation results. Though IRMOF-1 has a
      significantly higher adsorption capacity than silicalite and C168 schwarzite, the
      adsorption selectivity of CO2 over CH4 is found to be similar in all three
      adsorbents.

PMID- 17209618
TI  - Effect of sequential layer-by-layer surface modifications on the surface energy
      of plasma-modified poly(dimethylsiloxane).
AB  - Surface-initiated grafting of N,N-dimethylacrylamide, styrenesulfonate (SS), and
      (ar-vinylbenzyl)trimethylammonium chloride (VBTAC) from microwave plasma
      carboxylated, initiator-functionalized poly(dimethylsiloxane) (PDMS) surfaces was
      accomplished utilizing reversible addition-fragmentation chain transfer (RAFT)
      polymerization. Surface spectroscopic attenuated total reflectance (ATR) FT-IR
      analysis and atomic force microscopy (AFM) measurements were utilized to
      determine surface grafting and morphological surface features. The VBTAC-grafted
      PDMS provided a smooth, hydrophilic cationic surface for creating layer-by-layer
      (LBL) surfaces via alternating deposition of well-defined poly(SS) and
      poly(VBTAC), also prepared via aqueous RAFT. Comparisons of the ATR FT-IR spectra
      of the LBL assemblies and those of respective anionic poly(SS) and cationic
      poly(VBTAC) components confirmed strong electrostatic complexation of a fraction
      of the sulfonate and quarternary ammonium species in the layers as well as the
      existence of noncomplexed species. AFM images of surface topology indicated the
      presence of domains, likely phase-separated segments of the respective
      homopolymers, as well as interlayer mixing. The employed LBL methodology results
      in formation of stable, highly hydrophilic surfaces on a PDMS substrate. To our
      knowledge, this is the first study that illustrates surface functionalization of
      PDMS using microwave plasma and RAFT polymerization, followed by LBL deposition
      of polyelectrolytes.

PMID- 17209619
TI  - Study of the packing density and molecular orientation of bimolecular self
      assembled monolayers of aromatic and aliphatic organosilanes on silica.
AB  - Bimolecular self-assembled monolayers (SAMs) of aromatic and aliphatic
      chlorosilanes were self-assembled onto silica, and their characteristics were
      established by contact angle measurement, near-edge X-ray absorption fine
      structure spectroscopy, and Fourier transform infrared spectroscopy. Three
      aromatic constituents (phenyltrichlorosilane, benzyltrichlorosilane, and
      phenethyltrichlorosilane) were studied in combination with four aliphatic
      coadsorbates (butyltrichlorosilane, butyldimethylchlorosilane,
      octadecyltrichlorosilane, and octadecyldimethylchlorosilane). Our results
      demonstrate that whereas SAMs made of trichlorinated organosilanes are densely
      packed, SAMs prepared from monochlorinated species are less dense and poorly
      ordered. In mixed systems, trichlorinated aromatics and trichlorinated aliphatics
      formed SAMs with highly tunable compositions; their surfaces were compositionally
      homogeneous with no large-scale domain separation. The homogeneous nature of the
      resulting SAM was a consequence of the formation of in-plane siloxane linkages
      among neighboring molecules. In contrast, when mixing monochlorinated aliphatics
      with trichlorinated aromatics, molecular segregation occurred. Although the two
      shortest aromatic species did not display significant changes in orientation upon
      mixing with aliphatics, the aromatic species with the longest polymethylene
      spacer, phenethyltrichlorosilane, displayed markedly different orientation
      behavior in mixtures of short- and long-chain aliphatics.

PMID- 17209620
TI  - Specificity and sensitivity of fluorescence labeling of surface species.
AB  - FLOSS (fluorescence labeling of surface species) enables one to identify and
      quantify very low concentrations of surface functional groups. Unlike most
      surface analytical techniques, FLOSS can provide absolute, as well as relative,
      surface coverage determination. However, as with any other surface derivatization
      technique, FLOSS provides a lower limit to surface coverage. The specificity of
      FLOSS for a particular functional group is the key to this application. In one
      FLOSS protocol, amine-modified dyes are used to label surface aldehyde groups.
      However, amine-modified dyes, in principle, can bind to both aldehyde and
      carboxyl groups, limiting specificity. In this paper, we report that the FLOSS
      protocol devised results in less than 0.5 % of the carboxyl-modified dyes binding
      to the surface amine groups. Therefore, the presence of carboxyl groups on the
      surface should have a limited effect on the detection of aldehyde groups by amine
      modified dye. Quenching of fluorescence can potentially affect quantitative
      measurements. To address this issue, the densities of surface functional groups
      of CHO-, NH2-, and epoxy-coated glass surfaces were quantified using FLOSS and
      compared to surface densities estimated by other methods. The FLOSS technique was
      extended to glass surfaces by using visible absorbing and emitting dyes. The
      lower detection limit is on the order of 10(9) groups/cm2.

PMID- 17209621
TI  - Mimicking a Stenocara beetle's back for microcondensation using plasmachemical
      patterned superhydrophobic-superhydrophilic surfaces.
AB  - A simple two-step plasmachemical methodology is outlined for the fabrication of
      microcondensor surfaces. This comprises the creation of a superhydrophobic
      background followed by pulsed plasma deposition of a hydrophilic polymer array.
      Microcondensation efficiency has been explored in terms of the chemical nature of
      the hydrophilic pixels and their dimensions. These results are compared to the
      hydrophilic-hydrophobic pattern present on the Stenocara beetle's back, which is
      used by the insect to collect water in the desert. Potential applications include
      fog harvesting, microfluidics, and biomolecule immobilization.

PMID- 17209622
TI  - Trifluoperazine causes a disturbance in glycerophospholipid monolayers containing
      phosphatidylserine (PS): effects of pH, acyl unsaturation, and proportion of PS.
AB  - We have studied the interaction of trifluoperazine (TFP) with monolayers of
      various glycerophospholipids at 37 degrees C. TFP (1-10 microM) had little effect
      on surface pressure/molecular area isotherms in monolayers (on pure water) of
      dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylethanolamine but
      greatly increased the mean molecular area (mma) of dipalmitoylphosphatidylserine;
      the increment was greatest between 0 and 1 microM, and a further increase to 10
      microM TFP gave only a slight increase in mma. With phosphatidylserine (PS)
      containing stearoyl and varying acyls in the sn-1 and -2 positions, respectively,
      TFP increased the mma in a manner that depended on the number of double bonds and
      chain length. In mixtures of DPPC with two of these PS species the TFP-induced
      mma of the monolayers (on buffer, pH 7.4) increased linearly with the proportion
      of PS. Both PS and TFP have ionizable groups, and the TFP-induced mma increase
      had optima at pH 5.0 and 7.0. We conclude that the TFP-PS interaction is mainly,
      but not entirely, driven by electrostatic interactions between the TFP cation and
      PS headgroup anion, with an insertion of the phenothiazine moiety among the acyls
      in the monolayer that depends on the packing of the acyls.

PMID- 17209623
TI  - Synthesis and structural characterization of glucopyranosylamide films on gold.
AB  - Self-assembled monolayers (SAMs) of glucose derivatives on gold have been
      prepared from alpha- and beta-glucopyranosylamide derivatives. The glucosyl
      conjugates were synthesized stereoselectively via the in situ generation of
      glucosyl isoxazolines followed by treatment with thiopyridyl esters. The
      resulting film structures were characterized by atomic force microscopy,
      reflection Fourier transform infrared spectroscopy, and X-ray photoelectron
      spectroscopy. The experimental data indicated that alpha- or beta-linked
      glucopyranosylamide derivatives with free hydroxyl groups attach to gold via the
      thiol linker. Both derivatives form monolayer films with high packing densities-
      comparable to those typically observed for alkanethiol monolayers on gold.
      Acetate analogues of these conjugates do not form SAMs on gold; they form
      multilayered films under identical deposition conditions.

PMID- 17209624
TI  - Specific binding of GM1-binding peptides to high-density GM1 in lipid membranes.
AB  - The ganglioside Galbeta1-3GalNAcbeta1-4(Neu5Acalpha2-3)Galbeta1-4Glcbeta1-1'Cer
      (GM1) is an important receptor. We have previously identified GM1-binding
      peptides based on affinity selection from a random peptide library. In the
      present study, we determined the amino acids essential for binding GM1 and
      investigated the specific interaction with GM1 in the lipid membrane. Arginines
      and aromatic amino acids in the consensus sequence (W/F)RxL(xP/Px)xFxx(Rx/xR)xP
      contributed to the ability of the peptides to bind GM1. The peptide p3,
      VWRLLAPPFSNRLLP, having the consensus sequence, showed high affinity for GM1 with
      a dissociation constant of 1.2 microM. Furthermore, the density-dependent binding
      of p3 was investigated using mixed monolayers of GM1 and Glcbeta1-1'Cer (GlcCer).
      p3 binds preferentially to high-density GM1, and its interaction with GM1 was
      found to be cooperative based on a Hill plot. These results indicated that a
      lateral assembly of GM1 molecules was required for the recognition of
      carbohydrates by p3. The GM1-binding peptide played a role as a unique anti-GM1
      probe differing from the cholera toxin B subunit or antibodies.

PMID- 17209625
TI  - Spatially controlled cell adhesion via micropatterned surface modification of
      poly(dimethylsiloxane).
AB  - Spatial control of cell growth on surfaces can be achieved by the selective
      deposition of molecules that influence cell adhesion. The fabrication of such
      substrates often relies upon photolithography and requires complex surface
      chemistry to anchor adhesive and inhibitory molecules. The production of simple,
      cost-effective substrates for cell patterning would benefit numerous areas of
      bioanalytical research including tissue engineering and biosensor development.
      Poly(dimethylsiloxane) (PDMS) is routinely used as a biomedical implant material
      and as a substrate for microfluidic device fabrication; however, the low surface
      energy and hydrophobic nature of PDMS inhibits its bioactivity. We present a
      method for the surface modification of PDMS to promote localized cell adhesion
      and proliferation. Thin metal films are deposited onto PDMS through a physical
      mask in the presence of a gaseous plasma. This treatment generates topographical
      and chemical modifications of the polymer surface. Removal of the deposited metal
      exposes roughened PDMS regions enriched with hydrophilic oxygen-containing
      species. The morphology and chemical composition of the patterned substrates were
      assessed by optical and atomic force microscopies as well as X-ray photoelectron
      spectroscopy. We observed a direct correlation between the surface modification
      of PDMS and the micropatterned adhesion of fibroblast cells. This simple protocol
      generates inexpensive, single-component substrates capable of directing cell
      attachment and growth.

PMID- 17209626
TI  - Vesicle fission of giant unilamellar vesicles of liquid-ordered-phase membranes
      induced by amphiphiles with a single long hydrocarbon chain.
AB  - Vesicle fissions are very important processes of biomembranes in cells, but their
      mechanisms are not clear and are controversial. Using the single giant
      unilamellar vesicle (GUV) method, we recently found that low concentrations (less
      than the critical micelle concentration (CMC)) of lysophosphatidylcholine (lyso
      PC) induced the vesicle fission of GUVs of
      dipalmitoylphosphatidylcholine/cholesterol(6/4) (DPPC/chol(6/4)) membranes and
      sphingomyelin/cholesterol membranes (6/4) in the liquid-ordered (lo) phase. In
      this report, to elucidate its mechanism, we have investigated the effect of low
      concentrations (much less than their CMC) of other amphiphiles with a single long
      hydrocarbon chain (i.e., single long chain amphiphiles) on DPPC/chol(6/4) GUVs as
      well as the effect of the membrane composition on the lyso-PC-induced vesicle
      fission. We found that low concentrations of single long chain amphiphiles
      (lyosophosphatidic acid, octylglucoside, and sodium dodecyl sulfate) induced the
      shape change from a prolate to two spheres connected by a very narrow neck,
      indicating that the single long chain amphiphiles can be partitioned into the
      external monolayer in the lo phase of the GUV from the aqueous solution. As the
      single long chain amphiphile concentrations were increased, all of them induced
      vesicle fission of DPPC/chol(6/4) GUVs above their threshold concentrations. To
      elucidate the role of cholesterol in the single long chain amphiphile-induced
      vesicle fission, we investigated the effect of lyso-PC on GUVs of dioleoyl-PC
      (DOPC)/chol(6/4) membranes in the Lalpha phase; no vesicle fission occurred,
      indicating that cholesterol in itself did not play an important role in the
      vesicle fission. Finally, to elucidate the effect of the inclusion of DOPC in the
      lo-phase membrane of GUVs on the lyso-PC-induced vesicle fission of the
      DPPC/chol(6/4) GUV, we investigated the effect of low concentrations of lyso-PC
      on GUVs of DPPC/DOPC/chol membranes. With an increase in DOPC concentration in
      the membrane, the threshold concentration of lyso-PC increased. At and above 30
      mol % DOPC, no vesicle fission occurred. On the basis of these results, we have
      proposed a hypothesis of the mechanism of the single long chain amphiphile
      induced vesicle fission of a GUV of a lo-phase membrane.

PMID- 17209627
TI  - Electron transfer and ligand binding to cytochrome c' immobilized on self
      assembled monolayers.
AB  - We have successfully immobilized Allochromatium vinosum cytochrome c' on
      carboxylic acid-terminated thiol monolayers on gold and have investigated its
      electron-transfer and ligand binding properties. Immobilization could only be
      achieved for pH's ranging from 3.5 to 5.5, reflecting the fact that the protein
      is only sufficiently positively charged below pH 5.5 (pI = 4.9). Upon
      immobilization, the protein retains a near-native conformation, as is suggested
      by the observed potential of 85 mV vs SHE for the heme FeIII/FeII transition,
      which is close to the value of 60 mV reported in solution. The electron-transfer
      rate to the immobilized protein depends on the length of the thiol spacer,
      displaying distance-dependent electron tunneling for long thiols and distance
      independent protein reorganization for short thiols. The unique CO-induced dimer
      to-monomer transition observed for cytochrome c' in solution also seems to occur
      for immobilized cytochrome c'. Upon saturation with CO, a new anodic peak
      corresponding to the oxidation of an FeII-CO adduct is observed. CO binding is
      accompanied by a significant decrease in protein coverage, which could be due to
      weaker electrostatic interactions between the self-assembled monolayer and
      cytochrome c' in its monomeric form as compared to those in its dimeric form. The
      observed CO binding rate of 24 M-1 s-1 is slightly slower than the binding rate
      in solution (48 M-1 s-1), which could be due to electrostatic protein-electrode
      interactions or could be the result of protein crowding on the surface. This
      study shows that the use of carboxyl acid-terminated thiol monolayers as a
      protein friendly method to immobilize redox proteins on gold electrodes is not
      restricted to cytochrome c, but can also be used for other proteins such as
      cytochrome c'.

PMID- 17209628
TI  - Self-assembly, DNA complexation, and pH response of amphiphilic dendrimers for
      gene transfection.
AB  - Cationic lipids and polymers are routinely used for cell transfection, and a
      variety of structure-activity relation data have been collected. Few studies,
      however, focus on the structural aspects of self-assembly as a crucial control
      parameter for gene delivery. We present here the observations collected for a set
      of cationic dendritic amphiphiles based on a stiff tolane core (1-4) that are
      built from identical subunits but differ in the number and balance of their
      hydrophobic and cationic hydrophilic moieties. We established elsewhere that
      vectors 3 and 4 have promising transfection properties. Scanning probe microscopy
      (AFM, STM), cryo-transmission electron microscopy (cryo-TEM), and Langmuir
      techniques provide insight into the self-assembly properties of the molecules
      under physiological conditions. Furthermore, we present DNA and pH "jump"
      experiments where we study the response of Langmuir films to a sudden increase in
      DNA concentration or a drop in pH. We find that the primary self-assembly of the
      amphiphile is of paramount importance and influences DNA binding, serum
      sensitivity, and pH response of the vector system.

PMID- 17209629
TI  - Cell adhesion on nanofibrous polytetrafluoroethylene (nPTFE).
AB  - Here, we described the in vitro biocompatibility of a novel nanostructured
      surface composed of PTFE as a potential polymer for the prevention of adverse
      host reactions to implanted devices. The foreign body response is characterized
      at the tissue-material interface by several layers of macrophages and large
      multinucleated cells known as foreign body giant cells (FBGC), and a fibrous
      capsule. The nanofibers of nanofibrous PTFE (nPTFE) range in size from 20 to 30
      nm in width and 3-4 mm in length. Glass surfaces coated with nPTFE (produced by
      jet-blowing of PTFE 601A) were tested under in vitro conditions to characterize
      the amount of protein adsorption, cell adhesion, and cell viability. We have
      shown that nPTFE adsorbs 495 +/- 100 ng of bovine serum albumin (BSA) per cm2.
      This level was considerably higher than planar PTFE, most likely due to the
      increase in hydrophobicity and available surface area, both a result of the
      nanoarchitecture. Endothelial cells and macrophages were used to determine the
      degree of cell adsorption on the surface of the nanostructured polymer. Both cell
      types were significantly more round and occupied less area on nPTFE as compared
      to tissue culture polystyrene (TCPS). Furthermore, a larger majority of the cells
      on the nPTFE were dead compared to TCPS, at dead-to-live ratios of 778 +/- 271 to
      1 and 23 +/- 5.6 to 1, respectively. Since there was a high amount of cell death
      (due to either apoptosis or necrosis), and the foreign body response is a form of
      chronic inflammation, an 18 cytokine Luminex panel was performed on the
      supernatant from macrophages adherent on nPTFE and TCPS. As a positive control
      for inflammation, lipopolysaccharide (LPS) was added to macrophages on TCPS to
      estimate the maximum inflammation response of the macrophages. From the data
      presented with respect to IL-1, TNF-alpha, IFN-gamma, and IL-5, we concluded that
      nPTFE is nonimmunogenic and should not yield a huge inflammatory response in
      vivo, and cell death observed on the surface of nPTFE was likely due to apoptosis
      resulting from the inability of cells to spread on these surface. On the basis of
      the production of IL-1, IL-6, IL-4, and GM-CSF, we concluded that FBGC formation
      on nPTFE may be decreased as compared to materials known to elicit FBGC formation
      in vivo.

PMID- 17209630
TI  - Methods of stretching DNA molecules using flow fields.
AB  - Using fluorescence microscopy, we compare the degree of adsorption and stretching
      of DNA onto surfaces achieved by published stretching methods that use fluid
      flow: molecular combing, spin-stretching, and air-blowing. Molecular combing uses
      a receding meniscus to stretch out and deposit the DNA onto a hydrophobic
      surface. In spin-stretching, we find that the effect of radial hydrodynamic flow
      created by the centrifugal force of the rotating disk is minimal and that the DNA
      is stretched out on a hydrophobic substrate by the moving meniscus. In air
      blowing, a jet of gas pushes liquid across a substrate, depositing stretched DNA
      molecules along the way. In our study, DNA molecules either combed or spin
      stretched onto hydrophobic surfaces stretch to a greater degree than those that
      are air-blown; fewer are deposited at pH 8.0 than at lower pH, apparently because
      at pH 8.0 DNA adhesion occurs primarily only at the DNA extremities and so avoids
      trapped regions of incompletely stretched DNA, with the side effect that more
      molecules avoid adhesion altogether. We find by high-speed video microscopy that
      there is complex droplet deformation and motion during air-blowing, which
      complicates the deposition and stretching process, leading to radial alignment.
      Our results are a first step toward understanding and optimizing the various
      proposed methods of DNA stretching and anchoring onto surfaces, which is
      important in studying their interactions with proteins.

PMID- 17209631
TI  - Synthesis, assembly, and optical properties of shape- and phase-controlled ZnSe
      nanostructures.
AB  - Shape-, size-, and phase-controlled ZnSe nanostructures were synthesized by
      thermolysis of zinc acetate and selenourea using liganding solvents of
      octadecylamine (ODA) and trioctylphosphineoxide (TOPO) at different molar ratios.
      Materials synthesized in pure ODA resulted in uniform ultranarrow nanorods and
      nanowires of 1.3 nm in diameter. Morphological change from nanowire to spherical
      particle of larger diameter occurs with increasing TOPO/ODA ratio. Variation of
      the TOPO content in the mixed solvent also allows control of the crystallographic
      phase of ZnSe (wurtzite or zinc blende). The conditions and mechanisms of shape
      and phase control are discussed. Ultra-high-density networks of the ordered wires
      are achieved using the Langmuir-Blodgett technique in a single step as an
      essential stage on the route to ultra-high-density semiconductor nanocircuit
      fabrication.

PMID- 17209632
TI  - Lack of association between a cationic protein and a cationic fluorosurfactant.
AB  - Surface tension, 19F and 1H NMR spectroscopy, and cryotransmission electron
      microscopy are used to characterize the state of association in aqueous solutions
      of a fluorosurfactant CF3(CF2)nSO2NH(CH2)3-4N(CH3)3+ I- (n = 8, 6) with and
      without lysozyme added. In the absence of lysozyme, we find monomers, small
      aggregates, and large vesicles to coexist, with the individual fluorosurfactant
      molecules exchanging slowly (>1 ms) among those states. When both lysozyme and
      fluorosurfactant are present in the solution, they have no measurable influence
      on the physical state of the other. In contrast, a hydrogenated cationic
      surfactant with the same headgroup, hexadecyltrimethylammonium bromide, is shown
      to associate to lysozyme.

PMID- 17209633
TI  - Chain dynamics in microgels: poly(N-vinylcaprolactam-co-N-vinylpyrrolidone)
      microgels as examples.
AB  - Microgels are highly swollen colloids built up of flexible cross-linked chains.
      We studied the static and dynamic light scattering (LS) behavior of
      thermosensitive microgels based on N-vinylcaprolactam and N-vinylpyrrolidone
      prepared by precipitation copolymerization in H2O (CP-1) and D2O (CP-2). Striking
      differences in behavior were observed in the two solvents. In both cases the
      angular dependence of static LS could reasonably well be described by a soft
      sphere model (J. Polym. Sci., Polym. Phys. Ed. 1982, 20, 157) with small
      deviations at large qRg. At temperatures larger than the collapse temperatures,
      the CP-1 sample in water started to aggregate whereas the CP-2 sample in D2O
      showed no association and developed the expected change toward hard sphere
      behavior. Dynamic LS permitted the determination of internal or segmental
      mobility. A remarkable shift toward large qRg was found for CP-1 compared to the
      behavior of linear chains. The dynamic behavior is clearly displayed in a plot of
      Gamma*(q) = (Gamma1(q)/q3)(eta0/kT), with Gamma1(q) the first cumulant of the
      field time correlation function and the common meaning of the other parameters. A
      long range of hard sphere behavior indicated the suppression of internal modes,
      but at large qRg the swollen microgel CP-1 in water displayed internal motions
      with a spectrum similar to that of Zimm relaxations. No internal mobility could
      be detected with the CP-2 sample in D2O. The behavior is in agreement with
      observations in the literature. The differences in the two similar solvents were
      attributed to the poorer solvent quality of D2O.

PMID- 17209634
TI  - Particle growth of hybrid materials followed by dynamic light scattering.
AB  - The hydrolysis of distannylated compounds in which the tin atoms are linked by an
      organic spacer has been studied under microemulsion conditions using dynamic
      light scattering and infrared spectroscopy. The experiments provided evidence
      that the growth of hybrid material particles occurs in the aqueous phase, outside
      the organic phase of the microemulsion. The growth rates of the particles were
      found to be strongly dependent on the nature of the spacers, a polymethylene
      chain inducing the fastest process. This different behavior was explained by a
      slower condensation process rather than a slower hydrolysis. The high surface
      areas measured for the hybrid materials could be explained by a possible coating
      of the hybrid particles by surfactant molecules, thus preventing either their
      growth or their aggregation.

PMID- 17209635
TI  - Reactive block copolymer vesicles with an epoxy wall.
AB  - Recently, block copolymer vesicles have attracted considerable attention because
      of their properties in encapsulation and release. To explore their applications
      in biorelated fields, functionalization of the polymer vesicle is necessary.
      Herein, a reactive unilamellar vesicle is reported by self-assembly of
      poly(ethylene oxide)-block-poly(glycidyl methacrylate) copolymer (PEO-b-PGMA) in
      solution. When water was added into the PEO-b-PGMA solution in THF, unilamellar
      vesicles were produced. If hydrophobic primary amine additives, such as
      hexamethylenediamine (HDA) and dodecylamine (DA), were introduced during block
      copolymer assembling, the vesicular morphology remained unchanged; instead, the
      amines reacted with the epoxys and the vesicles were fixed by cross-linking.
      Furthermore, when 3-aminopropyl trimethoxysilane (APS) was applied, the
      organic/inorganic hybrid vesicles were obtained, which were stable against the
      solvent change. Therefore, this research not only supplies a new way to fix the
      vesicular morphology but also a reactive vesicle scaffold for introducing
      functional species.

PMID- 17209636
TI  - Fabrication and thermal analysis of submicron silver tubes prepared from
      electrospun fiber templates.
AB  - Submicron silver tubes have been synthesized by a polymer-based template
      approach. Two different approaches to metallization, electroless deposition and
      exchange plating, were evaluated within the template approach. Silver films with
      average thickness approximately 50-100 nm were deposited on polycarbonate fibers
      approximately 400 nm in diameter by each technique, resulting in tubes with a
      diameter between 450 and 500 nm after thermal degradation of core fibers. These
      nanomaterials were characterized by scanning electron microscopy (SEM), energy
      dispersive spectroscopy (EDS), and scanning thermal microscopy. The thermal
      conductivity of the silver submicron tubes was found to differ depending on the
      method of preparation, with tubes from electroless plating possessing relative
      thermal conductivity values that were 1 order of magnitude higher than that from
      exchange plating, 3000 W/m x K and 660 W/m x K, respectively. Interestingly,
      these results indicate that silver submicron tubes possess higher thermal
      conductivity than the bulk metal. This observation is discussed in the context of
      the continuous conduction path of the tubes and their high surface area-to-volume
      ratio.

PMID- 17209637
TI  - Molecular dynamics simulation study on controlling the adsorption behavior of
      polyethylene by fine tuning the surface nanodecoration of graphite.
AB  - Molecular dynamics simulations are applied to study the adsorption of
      polyethylene with different chain lengths on patterned graphite surfaces that
      contain nanoscale protrusions. The influence of the nanostructure on the strong
      attractive interaction inherently in the hydrophobic polyethylene and hydrophobic
      graphite system is investigated by modifying the top surface area and the height
      and the shape of the protrusions. The results are analyzed in terms of the chain
      configuration, the adsorption energy, the global orientational order parameter,
      and the normalized surface-chain contacting pair number in the first adsorption
      layer. When the size of the protrusion increases, the adsorption energy, the
      order parameter, and the normalized surface-chain contacting pair number decrease
      at a fixed chain length. When the size of the protrusion is fixed, the average
      adsorption energy per monomer and the order parameter decrease with increasing
      chain length because of the stronger intramolecular interactions between the
      monomers. Changing the protrusion shape in a suitable way will effectively reduce
      the strong surface-chain interaction.

PMID- 17209638
TI  - Formation of supramolecular nanobelt arrays consisting of cobalt(II) "picket
      fence" porphyrin on Au surfaces.
AB  - Adlayers of cobalt(II) 5,10,15,20-tetrakis(alpha,alpha,alpha,alpha-2
      pivalamidophenyl)porphyrin (CoTpivPP) were prepared by immersing either Au(111)
      or Au(100) substrate in a benzene solution containing CoTpivPP molecules, and
      they were investigated in 0.1 M HClO4 and 0.1 M H2SO4 by cyclic voltammetry and
      in situ scanning tunneling microscopy (STM). The adlayer structure and
      electrochemical properties of CoTpivPP are compared to those of 5,10,15,20
      tetraphenyl-21H,23H-porphine cobalt(II) (CoTPP). Characteristic nanobelt arrays
      consisting of CoTpivPP molecules were produced on both Au(111) and Au(100)
      surfaces. The stability of the nanobelt arrays was controlled by manipulating the
      electrode potential. On the other hand, the formation of nanobelt arrays
      consisting of O2-adducted CoTpivPP molecules depended upon the crystallographic
      orientation of Au. The state of O2 trapped in the cavity of CoTpivPP was
      distinctly observed in STM images as a bright spot in the nanobelt array formed
      on reconstructed Au(100)-(hex) surface, but not on Au(111) surface. This result
      suggests that the arrangement of underlying Au atoms plays an important role in
      the formation of nanobelt arrays with the sixth ligand coordination.

PMID- 17209639
TI  - Nanopatterning and fabrication of memory devices from layer-by-layer poly(3,4
      ethylenedioxythiophene)-poly(styrene sulfonate) ultrathin films.
AB  - A write-read-erasable memory device was fabricated on layer-by-layer (LbL)
      ultrathin films prepared from poly(3,4-ethylenedioxythiophene)-poly(styrene
      sulfonate) (PEDOT-PSS) and poly(diallyldimethylammonium chloride) (PDDA). By use
      of current-sensing atomic force microscopy (CS-AFM), nanopatterns were formed by
      applying a bias voltage between a conductive tip (Pt-coated Si3N4 cantilever) in
      contact with the polymer film and gold substrate. The dependence of the
      nanopatterns on film thickness, applied bias, and writing speed was studied.
      Moreover, the height of the patterns was 3-5 times higher than the original
      thickness of the films, opening the possibility for three-dimensional
      nanopatterning. The ability of the patterns to be erased after nanowriting was
      also investigated. By comparing the I-V characteristics under ambient conditions
      and under N2 environment, a joule-heating activated, water meniscus-assisted
      anion doping mechanism for the nanopatterning process was determined. Write-read
      erase memory device capability was demonstrated on the nanopatterns.

PMID- 17209640
TI  - Homocysteine-mediated reactivity and assembly of gold nanoparticles.
AB  - This paper reports the findings of an investigation of the reactivity and
      assembly of gold nanoparticles mediated by homocysteine (Hcys), a thiol
      containing amino acid found in plasma. The aim is to gain insight into the
      interparticle interaction and reactivity, which has potential application for the
      detection of thiol-containing amino acids. By monitoring the evolution of the
      surface plasmon resonance absorption and the dynamic light scattering of gold
      nanoparticles in the presence of Hcys, the assembly was shown to be dependent on
      the nature and concentration of the electrolytes, reflecting an effective
      screening of the diffuse layer around the initial citrate-capped nanoparticles
      that decreases the barrier to the Hcys adsorption onto the surface, and around
      the subsequent Hcys-capped nanoparticles that facilitate the zwitterion-type
      electrostatic interactions between amino acid groups of Hcys bound to different
      nanoparticles. A key element of the finding is that the interparticle zwitterion
      interaction of the Hcys-Au system is much stronger than the expectation for a
      simple Hcys or Au solution, a new phenomenon originating from the unique
      nanoscale interparticle interaction. The strength and reversibility of the
      interparticle zwitterion-type electrostatic interactions between amino acid
      groups are evidenced by the slow disassembly upon increasing pH at ambient
      temperatures and its acceleration at elevated temperature. These findings provide
      new insight into the precise control of interfacial interactions and reactivities
      between amino acids anchored to nanoparticles and have broad implications in the
      development of colorimetric nanoprobes for amino acids.

PMID- 17209641
TI  - Measuring molecular order in poly(3-alkylthiophene) thin films with polarizing
      spectroscopies.
AB  - We measured the molecular order of poly(3-alkylthiophene) chains in thin films
      before and after melting through the combination of several polarized photon
      spectroscopies: infrared (IR) absorption, variable angle spectroscopic
      ellipsometry (SE), and near-edge X-ray absorption fine structure (NEXAFS). The
      data from the various techniques can be uniformly treated in the context of the
      dielectric constant tensor epsilon for the film. The combined spectroscopies
      allow determination of the orientation distribution of the main-chain axis (SE
      and IR), the conjugated pi system normal (NEXAFS), and the side-chain axis (IR).
      We find significant improvement in the backbone order of the films after
      recrystallization of the material at temperatures just below the melting
      temperature. Less aggressive thermal treatments are less effective. IR studies
      show that the changes in backbone structure occur without significant alteration
      of the structure of the alkyl side chains. The data indicate that the side chains
      exhibit significant disorder for all films regardless of the thermal history of
      the sample.

PMID- 17209642
TI  - Comparison of dansylated aminopropyl controlled pore glass solvated by molecular
      and ionic liquids.
AB  - We compare how (i) four ionic liquids (ILs) (1-butyl-3-methylimidazolium
      tetrafluoroborate ([C4mim][BF4]), 1-butyl-3-methylimidazolium
      bis(trifluoromethylsulfonyl)imide ([C4mim][Tf2N]), 1-butyl-1-methylpyrrolidinium
      bis(trifluoromethylsulfonyl)imide ([C4mpy][Tf2N]), and
      trihexyltetradecylphosphonium bis(trifluoromethylsulfonyl)imide
      ([P(C6)3C14][Tf2N])) and (ii) two conventional molecular liquids (methanol and 1
      octanol) solvate/wet luminescent organic moieties that are covalently attached to
      the surface of silica controlled pore glass (CPG). A series of aminopropyl CPG
      particles that have been covalently tagged with the solvatochromic fluorescent
      probe group dansyl were used in this study. The results demonstrate that ILs
      solvate/wet the silica surface differently in comparison to molecular liquids
      (MLs). Specifically, when comparing ILs and MLs that appear to solvate the free
      probe, dansylpropylsulfonamide (DPSA), equally in solution, we find that ILs do
      not solvate/wet the silica surfaces as well as the corresponding MLs. The cation
      component in these ILs is the significant factor in how the ILs solvate/wet
      silica surfaces. Solvation/wetting of surface-bound species at a silica surface
      depends on the cation size. Chlorosilane end-capping of the surface silanol and
      amine residues attenuates the cation's affects.

PMID- 17209643
TI  - Synthesis of nanocrystal-polymer transparent hybrids via polyurethane matrix
      grafted onto functionalized CdS nanocrystals.
AB  - We reported the first synthesis of CdS nanocrystal-polymer transparent hybrids by
      using polyurethane (PU) grafted onto quantum dots (QDs) CdS nanocrystals. In a
      typical run, the appropriate amounts of cadmium chloride (CdCl2) and sodium
      sulfide (Na2S) in the presence of 2-mercaptoethanol (ME) as the organic ligand
      are well dispersed in H2O/DMF solution without any aggregation. From a
      combination of transmission electron microscopy (TEM) and a computing method of
      Brus's model according to UV-vis absorption spectra, the particle size of as
      prepared hydroxyl-coated CdS nanocrystals is about 5 nm. Then, PU-CdS transparent
      nanocomposites hybrids were synthesized by a two-step reaction. The effect of the
      different ratios of ME/Cd2+ and H2O/DMF on the resulting particle size of CdS
      nanocrystals was investigated by UV-vis absorption measurements. FT-IR and TGA
      characterizations indicate the formation of robust bonding between CdS
      nanocrystals and the organic ligand. The fluorescence measurement shows that CdS
      PU hybrids exhibit good optical properties.

PMID- 17209644
TI  - Phase separation in liquid crystalline mesophases of [Co(H2O)6]X2:P65 Systems (X
      = NO3-, Cl-, or ClO4-).
AB  - Transition-metal aqua complex salts [M(H2O)6]X2 (where M is Mn(II), Co(II),
      Ni(II), Zn(II), or Cd(II) and X is NO3-, Cl-, or ClO4-) can be dissolved in
      triblock poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)
      copolymers (Pluronics, such as P65) to form homogeneous liquid crystalline (LC)
      mesophases. However, the [Co(H2O)6]X2:P65 LC mesophases slowly undergo phase
      separation into a disordered ion-free phase and an ordered ion-rich LC mesophase.
      The phase separation also takes place in the two-salt systems
      [Co(H2O)6](NO3):[Co(H2O)6](ClO4)2:P65 in which the ion-free disordered domains
      separate out from the initially ordered homogeneous mesophase. The phase
      separation results in a physical mixture of a hexagonal nitrate-rich and cubic
      perchlorate-rich LC and disordered ion-free domains in the mixed salt systems.
      The driving force in the phase separation in the [Co(H2O)6]X2:P65 system is
      Co(II)-catalyzed aerobic oxidation of P65 into ester and/or other oxidation
      products. The separation of ions in the [Co(H2O)6](NO3)2:[Co(H2O)6](ClO4)2:P65
      system is related to the mesostructures of the two-salt systems that are
      different, hexagonal in the [Co(H2O)6](NO3)2:P65 system and cubic in the
      [Co(H2O)6](ClO4)2:P65 system. There is no visible phase separation in the other
      transition-metal salt:P65 systems. The phase separation in the [Co(H2O)6]X2:P65
      systems can also be eliminated by keeping the mesophase under a N2 atmosphere.

PMID- 17209645
TI  - General synthesis and delamination of highly crystalline transition-metal-bearing
      layered double hydroxides.
AB  - In this paper, we describe a general process for the synthesis and delamination
      of a family of highly crystalline Al-based and transition-metal-bearing layered
      double hydroxides (LDHs). Large-sized and monodispersed hexagonal platelike
      particles of binary-component M(II)-Al-CO3 and ternary-component M(II)-M'(II)-Al
      CO3 LDHs (M(II) and M'(II) = Fe, Co, Ni, or Zn) were prepared at first by the
      urea method under optimized conditions. These CO32--LDHs were converted into
      other monovalent-anion-containing LDHs by means of a salt-acid treatment and
      subsequent anion-exchange processes. Finally, well-defined LDH nanosheets were
      obtained by delamination of NO3--LDHs in formamide.

PMID- 17209646
TI  - Size control of mesoscale aqueous assemblies of quantum dots and block
      copolymers.
AB  - Dropwise addition of water to blend solutions of block copolymer-stabilized
      quantum dots (QDs) and amphiphilic block copolymer stabilizing chains PS(665)-b
      PAA(68) (PS = polystyrene, PAA = poly(acrylic acid)) in DMF induces self-assembly
      to form photoluminescent mesoscale QD/block copolymer colloids in water termed QD
      compound micelles (QDCMs). Here we demonstrate reproducible kinetic control of
      QDCM particle size and chain stretching within the external PAA stabilizing layer
      via changes in the initial polymer concentration and rate of water addition. By
      increasing the initial polymer concentration or decreasing the rate of water
      addition for a constant blend composition, larger QDCM particles are obtained.
      From a combination of transmission electron microscopy and dynamic light
      scattering, the thickness of the external PAA layer is determined for various
      QDCM sizes, showing that PAA stretching in the external brush layer increases
      with increasing particle size, reaching the limit of fully extended chains for
      sufficiently large particles. The photoluminescence spectra from QDCMs in pure
      water indicate that photoluminescence properties of the block copolymer
      stabilized QD building blocks are retained during self-assembly. The demonstrated
      control of mesoscale particle size and conformation of the stabilizing PAA layer,
      among other related structural parameters, via simple variation of experimental
      conditions is a promising step toward the application of QDCM assemblies in
      photonics and biolabeling.

PMID- 17209647
TI  - Enhanced conductivity of thin film polyaniline by self-assembled transition metal
      complexes.
AB  - In a recent study, the transition metal complex, cis-dichlorobis(2-,2'
      dipyridyl)ruthenium (II) (Ru(bpy)2Cl2), and the macrocycle Ru(TPP)CO (TPP:-
      tetraphenylporphine) were bound to pyridine terminated self-assembled monolayers
      on quartz. Following modification of the quartz surface with metal complexes, the
      conducting polymer polyaniline was deposited via in situ polymerization. The
      sheet conductivity (as measured by the four-probe method) of the resulting
      polyaniline films deposited onto Ru(bpy)2Cl2 and Ru(TPP)CO surfaces was
      significantly enhanced relative to films deposited onto unmodified quartz. It is
      postulated that either the macrocycle or the transition metal complex-modified
      surface interacts with the conducting polymer as it is forming, resulting in a
      more ordered expanded coil conformation for the polymer. The net result of such
      an interaction is a thin film possessing significantly greater electrical
      conductivity.

PMID- 17209648
TI  - Design of polymeric stabilizers for size-controlled synthesis of monodisperse
      gold nanoparticles in water.
AB  - A new methodology is described for the one-step aqueous preparation of highly
      monodisperse gold nanoparticles with diameters below 5 nm using thioether- and
      thiol-functionalized polymer ligands. The particle size and size distribution was
      controlled by subtle variation of the polymer structure. It was shown that
      poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) were the most
      effective stabilizing polymers in the group studied and that relatively low molar
      mass ligands (approximately 2500 g/mol) gave rise to the narrowest particle size
      distributions. Particle uniformity and colloidal stability to changes in ionic
      strength and pH were strongly affected by the hydrophobicity of the ligand end
      group. "Multidentate" thiol-terminated ligands were produced by employing
      dithiols and tetrathiols as chain-transfer agents, and these ligands gave rise to
      particles with unprecedented control over particle size and enhanced colloidal
      stability. It was found throughout that dynamic light scattering (DLS) is a very
      useful corroboratory technique for characterization of these gold nanoparticles
      in addition to optical spectroscopy and TEM.

PMID- 17209649
TI  - Counterions and water in polyelectrolyte multilayers: a tale of two polycations.
AB  - Attenuated total internal reflectance Fourier transform infrared, ATR-FTIR,
      spectroscopy was used to compare the water uptake and doping within
      polyelectrolyte multilayers made from poly(styrene sulfonate), PSS, and a
      polycation, either poly(allylamine hydrochloride), PAH, or
      poly(diallyldimethylammonium chloride), PDADMAC. Unlike PDADMA/PSS multilayers,
      whose water content depended on the solution ionic strength, PAH/PSS multilayers
      were resistant to doping by NaCl to a concentration of 1.2 M. Using (infrared
      active) perchlorate salt, the fraction of residual counterions in PDADMA/PSS and
      PAH/PSS was determined to be 3% and 6%, respectively. The free energy of
      association between the polymer segments, in the presence of NaClO4, was about 5
      kJ mol-1 and -10 kJ mol-1, respectively, for PDADMA/PSS and PAH/PSS, indicating
      the relatively strong association between the polymer segments in the latter
      relative to the former. Varying the pH of the solution in contact with the
      PAH/PSS multilayer revealed a transition to a highly swollen state, interpreted
      to signal protonation of PAH under much more basic conditions than the pKa of the
      solution polymer. The increase in the multilayer pKa suggested an interaction
      energy for PAH/PSS in NaCl of ca. 16 kJ mol-1.

PMID- 17209650
TI  - Structure and dewetting behavior of polyhedral oligomeric silsesquioxane-filled
      polystyrene thin films.
AB  - Polyhedral oligomeric silsesquioxane (POSS) meets increasing interest as a
      building unit for inorganic-organic hybrid materials. The incorporation of
      cyclopentyl-substituted POSS (CpPOSS) into polystyrene (PS) thin films led to an
      inhibition of dewetting. In this paper, the dispersion state of CpPOSS in the
      CpPOSS/PS hybrid films and, furthermore, the relationships between the structure
      and dewetting inhibition effect are discussed. Structural analysis of the hybrid
      films revealed that CpPOSS segregated to the film surface and crystallized. The
      segregation of CpPOSS to the surface changes the surface free energy and
      spreading coefficient of the film. Interfacial structure was also roughened by
      the segregation of CpPOSS, which can contribute to the inhibition of dewetting by
      pinning the contact line of the PS film with the substrate. The inhibition of
      dewetting can be attributed to the modification of the film surface and interface
      by the segregation of CpPOSS.

PMID- 17209651
TI  - Quantitative electrochemical and electrochromic behavior of terthiophene and
      carbazole containing conjugated polymer network film precursors: EC-QCM and EC
      SPR.
AB  - A comparative analysis of the copolymerization behavior between an electro-active
      terthiophene and a carbazole moiety of a conjugated polymer precursor was
      investigated using electrochemical and hyphenated electrochemical methods. Five
      different precursor polymers were first synthesized and characterized using NMR,
      IR, and GPC. The polymers include homopolymers of individual electro-active
      groups (P3T, P-CBZ) and different compositions of 25, 50, and 75% (P3TC-25,
      P3TC50, and P3TC-75) with respect to the two electro-active groups. Since the
      oxidation potentials of terthiophene and carbazole lie very close to each other,
      highly cross-linked copolymer films of varying extent were produced depending on
      the composition. The copolymerization extent was found to be dependent primarily
      on the amount of the terthiophene, which in this case provided for a more
      efficient carbazole polymerization and copolymerization than with just carbazole
      alone (homopolymer). The extent of copolymerization, electrochromic properties,
      and viscoelastic changes was quantitatively investigated using a number of
      hyphenated electrochemistry techniques: spectro-electrochemistry, electrochemical
      quartz crystal microbalance studies (EC-QCM), and electrochemical surface plasmon
      resonance spectroscopy (EC-SPR). Each technique revealed a unique aspect of the
      electrocopolymerization behavior that was used to define structure-property
      relationships and the deposition/copolymerization mechanism.

PMID- 17209652
TI  - Electrowetting of nonwetting liquids and liquid marbles.
AB  - Transport of a water droplet on a solid surface can be achieved by differentially
      modifying the contact angles at either side of the droplet using capacitive
      charging of the solid-liquid interface (i.e., electrowetting-on-dielectric) to
      create a driving force. Improved droplet mobility can be achieved by modifying
      the surface topography to enhance the effects of a hydrophobic surface chemistry
      and so achieve an almost complete roll-up into a superhydrophobic droplet where
      the contact angle is greater than 150 degrees . When electrowetting is attempted
      on such a surface, an electrocapillary pressure arises which causes water
      penetration into the surface features and an irreversible conversion to a state
      in which the droplet loses its mobility. Irreversibility occurs because the
      surface tension of the liquid does not allow the liquid to retract from these
      fixed surface features on removal of the actuating voltage. In this work, we show
      that this irreversibility can be overcome by attaching the solid surface features
      to the liquid surface to create a liquid marble. The solid topographic surface
      features then become a conformable "skin" on the water droplet both enabling it
      to become highly mobile and providing a reversible liquid marble-on-solid system
      for electrowetting. In our system, hydrophobic silica particles and hydrophobic
      grains of lycopodium are used as the skin. In the region corresponding to the
      solid-marble contact area, the liquid marble can be viewed as a liquid droplet
      resting on the attached solid grains (or particles) in a manner similar to a
      superhydrophobic droplet resting upon posts fixed on a solid substrate. When a
      marble is placed on a flat solid surface and electrowetting performed it spreads
      but with the water remaining effectively suspended on the grains as it would if
      the system were a droplet of water on a surface consisting of solid posts. When
      the electrowetting voltage is removed, the surface tension of the water droplet
      causes it to ball up from the surface but carrying with it the conformable skin.
      A theoretical basis for this electrowetting of a liquid marble is developed using
      a surface free energy approach.

PMID- 17209653
TI  - Structure of the electrical double layer on the aqueous solution side of the
      polarized interface between water and a room-temperature ionic liquid,
      tetrahexylammonium bis(trifluoromethylsulfonyl)imide.
AB  - The structure of the electrical double layer on the aqueous solution side has
      been studied by measuring electrocapillary curves at the polarized interface
      between a room-temperature ionic liquid (RTIL), tetrahexylammonium
      bis(trifluoromethylsulfonyl)imide, and water (W) at different concentrations of
      LiCl. Thermodynamic analysis of the electrocapillary curves indicates that Li+
      ions negatively adsorb at the point of zero charge. The adsorption of Li+ and Cl-
      ions in the polarized potential window of about 200 mV can be explained by the
      Gouy's double layer model, and the specific adsorption of Li+ and Cl- ions at the
      RTIL|W interface is negligible within the polarized potential window.

PMID- 17209654
TI  - Adsorption of tentacled tetragonal star connectors, C4R4-Co-C5(HgX)5, on mercury.
AB  - For future use in self-assembly of surface structures, the adsorption on the
      surface of mercury of a series of tetraphenylcyclobutadienecyclopentadienylcobalt
      double-decker sandwich complexes with five mercury and sulfur containing
      "tentacles" on the cyclopentadienyl deck has been examined by combined
      electrochemical and Langmuir trough techniques.

PMID- 17209655
TI  - Electrochemical quartz crystal microbalance studies of the rectified quantized
      charging of gold nanoparticle multilayers.
AB  - Electrochemical quartz crystal microbalance (EQCM) was employed to investigate
      the dynamics of rectified quantized charging of gold nanoparticle multilayers by
      in situ monitoring of the interfacial mass changes in aqueous solutions with
      varied electrolytes. EQCM measurements showed that interfacial mass changes only
      occurred at potentials more positive than the potential of zero charge (PZC),
      where nanoparticle quantized charging was well-defined, whereas in the negative
      potential regime where only featureless voltammetric responses were observed, the
      QCM frequency remained virtually invariant. This was ascribed to the fact that
      nanoparticle quantized charging was induced by the formation of ion-pairs between
      hydrophobic electrolyte anions (PF6-, ClO4-, BF4-, and NO3-) and positively
      charged gold nanoparticles. Based on the total frequency changes and the number
      of electrolyte anions adsorbed onto the particle layers, the number of water
      molecules that were involved in the ion-pairing processes was then quantitatively
      estimated at varied particle charge states, which was found to increase with
      increasing hydrophobicity of the anions. Additionally, the electron-transfer
      dynamics of the gold particle multilayers were also evaluated by electrochemical
      impedance measurements. It was found that the particle electron-transfer rate was
      about an order of magnitude slower than that of the ion diffusion and binding.

PMID- 17209656
TI  - Rapid proton-coupled electron-transfer of hydroquinone through phenylenevinylene
      bridges.
AB  - We describe the synthesis of two oligo(phenylene vinylene)s (OPVs) with a
      hydroquinone moiety and a thiol anchor group: 4-(2',5'-dihydroxystyryl)benzyl
      thioacetate and 4-[4'-(2' ',5' '-dihydroxystyryl)styryl]benzyl thioacetate.
      Monolayers on gold of these molecules were examined by electrochemical techniques
      to determine the electron transfer kinetics of the hydroquinone functionality
      (H2Q) through these delocalized tethers ("molecular wires") as a function of pH.
      Between pH 4 and 9, rate constants were ca. 100-fold faster than for the same H2Q
      functionality confined to the surface via alkane tethers. Also, in this same pH
      range rate constants were independent of the length of the OPV bridge. These new
      electroactive molecules in which the hydroquinone functionality is wired to the
      gold surface by means of OPV tethers should be useful platforms for constructing
      bioelectronic devices such as biosensors, biofuel cells, and biophotovoltaic
      cells with a fast response time.

PMID- 17209657
TI  - Biochemical interaction analysis on ATR devices: a wet chemistry approach for
      surface functionalization.
AB  - A new generic device suitable for the investigation of ligand-receptor
      interactions is presented. In particular, the research focused on optical
      waveguides constituted by an attenuated total internal reflection (ATR) element,
      transparent in the infrared and whose surfaces were activated in view of
      covalently binding a receptor. Silicon and germanium ATR elements were
      considered. The original method is based on the grafting of bifunctional spacer
      molecules directly at the surface of the germanium crystal, avoiding the
      deposition of an intermediate metal layer. The grafting of these binding
      molecules (under their N-hydroxysuccinimidyl ester forms) was performed either by
      wet chemistry or by photochemistry. The functionalized surfaces, which allow the
      binding of molecules bearing peripherical NH2 groups, were successfully used,
      e.g., for the detection of proteins (streptavidin) or of small molecules
      (biotin). In the latter case, the biotin was readily detected for concentrations
      as low as 10(-12) M.

PMID- 17209658
TI  - Controlling drop size and polydispersity using chemically patterned surfaces.
AB  - We explore numerically the feasibility of using chemical patterning to control
      the size and polydispersity of micrometer-scale drops. The simulations suggest
      that it is possible to sort drops by size or wetting properties by using an array
      of hydrophilic stripes of different widths. We also demonstrate that monodisperse
      drops can be generated by exploiting the pinning of a drop on a hydrophilic
      stripe. Our results follow from using a lattice Boltzmann algorithm to solve the
      hydrodynamic equations of motion of the drops and demonstrate the applicability
      of this approach as a design tool for micofluidic devices with chemically
      patterned surfaces.

PMID- 17209660
TI  - Inhibiting costimulatory activation of T cells : a viable treatment option for
      rheumatoid arthritis?
AB  - There is now good evidence that T cells play a central role in the inflammatory
      pathway that leads to the persistent synovitis that causes joint damage in
      rheumatoid arthritis (RA). T cells require two signals to become activated. The
      second step in the activation of T cells involves costimulatory pathways, the
      best described pathway being the binding of CD28 on T cells to CD80/86 on antigen
      presenting cells. This observation has led to the development of a new category
      of biological response modifier. Abatacept is a fusion protein (cytotoxic T
      lymphocyte-associated antigen-4 immunoglobulin [CTLA4Ig]); which blocks the
      binding of CD28 by avidly binding CD80/86. Without this costimulatory activation,
      the T cell becomes anergic. Abatacept has consistently been shown to improve the
      signs and symptoms of RA in phase II and phase III trials in patients with an
      inadequate response to methotrexate and anti-tumour necrosis factor (TNF)
      therapy. Onset of action is rapid and efficacy is maintained during the period of
      treatment. Recent trials have also provided evidence of improvement in quality-of
      life measures and radiographic progression. The safety profile to date has also
      been favourable and supports the theory that targeting naive T cells early in the
      inflammatory pathway will lead to immunomodulation rather than immunosuppression.
      The evidence produced so far suggests that abatacept will be a useful addition to
      the available therapies for patients with RA.

PMID- 17209661
TI  - Squalene synthase inhibitors : clinical pharmacology and cholesterol-lowering
      potential.
AB  - HMG-CoA reductase inhibitors (statins) reduce cardiovascular disease morbidity
      and mortality with a high level of safety. Nonetheless, there are substantial
      numbers of people who either do not tolerate statins or whose low-density
      lipoprotein (LDL) levels are not lowered adequately. For these reasons, there is
      a need to develop other cholesterol-lowering drugs. A target for these new agents
      is provided by the enzymes distal to HMG-CoA reductase in the cholesterol
      biosynthesis pathway. Two classes of drugs have been developed: (i) squalene
      synthase inhibitors, which act at the first committed step in cholesterol
      biosynthesis, distal to the mevalonate-farnesyl diphosphate pathway; and (ii)
      oxidosqualene cyclase inhibitors, which act distal to the squalene intermediate.
      Of these, squalene synthase inhibitors have received more attention and are the
      subject of this review. Squalene synthase inhibitors decrease circulating LDL
      cholesterol by the induction of hepatic LDL receptors in a similar manner to
      statins. They have fewer secondary effects mediated by a decrease in non
      cholesterol products of mevalonate metabolism distal to HMG-CoA reductase, but
      have the potential to increase intermediates proximal to squalene. Squalene
      synthase inhibitors are just now entering clinical trials and data on how
      effectively they lower LDL-cholesterol and how they compliment the actions of
      statins and other agents is awaited with considerable interest.

PMID- 17209662
TI  - Practical issues and challenges in the diagnosis and treatment of pulmonary
      sarcoidosis.
AB  - Sarcoidosis is a granulomatous disease with multisystem involvement. Diagnosis is
      generally easy to establish from the characteristic clinical and radiographic
      features. In India and other developing countries, tuberculosis is the closest
      clinical mimic and needs to be excluded before therapy for sarcoidosis is
      instituted. Tuberculin anergy and histopathological demonstration of
      characteristic compact granulomas help in the diagnosis of sarcoidosis.
      Corticosteroids constitute the mainstay of therapy for symptomatic pulmonary and
      most other forms of extrapulmonary sarcoidosis. Asymptomatic disease does not
      require any treatment, but milder forms may be treated with topical
      corticosteroids and symptomatic therapy. Alternative drugs such as cytotoxic
      agents, hydroxychloroquine and other agents are used either alone or in
      combination for the treatment of relapses and recurrences and refractoriness or
      in the presence of complications of corticosteroids. Treatment is usually
      continued for about a year, but it may need to be prolonged in patients with
      disease that persists and the response to therapy is delayed.

PMID- 17209664
TI  - Therapeutic applications of sildenafil citrate in the management of paediatric
      pulmonary hypertension.
AB  - Pulmonary hypertension is characterised by a progressive increase in pulmonary
      vascular resistance and a poor prognosis. The exact underlying mechanisms are
      still poorly understood; however, it is hypothesised that pulmonary medial
      hypertrophy and endothelial dysfunction lead to impaired production of
      vasodilators such as nitric oxide (NO) and prostacyclin, and increased expression
      of vasoconstrictors such as endothelin-1. The current treatment modalities for
      pulmonary hypertension include conventional supportive therapies and more
      specific pharmacological therapies that are targeted at abnormalities of
      endothelial function. NO and phosphodiesterase type 5 (PDE5) inhibitors induce
      pulmonary vasodilation by increasing intracellular cyclic guanosine monophosphate
      (cGMP) concentrations. Sildenafil citrate is a highly selective inhibitor of
      PDE5. Investigations in animal models and recent clinical case reports with some
      studies in the paediatric population suggest that sildenafil may be a promising
      agent in treating pulmonary hypertension. The effect of sildenafil on pulmonary
      vasculature appears to be independent of the underlying cause, thereby providing
      a role in idiopathic pulmonary arterial hypertension (PAH), PAH associated with
      congenital heart disease, pulmonary hypertension secondary to lung disease or
      persistent pulmonary hypertension of the newborn. It may also be beneficial in
      postoperative pulmonary hypertension and in neonates who are difficult to wean
      from inhaled NO. It is easily administered and effective, and has minimal
      systemic adverse effects. Although the reported results in children with
      pulmonary hypertension are promising, it is an experimental drug and large-scale
      randomised controlled studies are required to validate the safety, efficacy and
      dosage in the paediatric population.

PMID- 17209663
TI  - Serotonergic drugs : effects on appetite expression and use for the treatment of
      obesity.
AB  - Over 35 years of research suggests that endogenous hypothalamic serotonin (5
      hydroxytryptamine) plays an important part in within-meal satiation and post-meal
      satiety processes. Thus, the serotonin system has provided a viable target for
      weight control, critical to the action of at least two effective anti-obesity
      treatments, both producing clinically significant weight loss over a year or
      more. Numerous serotonin receptor subtypes have been identified; of these,
      serotonin 5-HT1B and 5-HT2C receptors have been specifically recognised as
      mediators of serotonin-induced satiety.A number of serotonergic drugs, including
      selective serotonin reuptake inhibitors (SSRIs), dexfenfluramine and 5-HT2C
      receptor agonists, have been shown to significantly attenuate rodent bodyweight
      gain. This effect is strongly associated with marked hypophagia and is probably
      mediated by the hypothalamic melanocortin system. Additionally, sibutramine,
      dexfenfluramine, fluoxetine and the 5-HT2C receptor agonist
      chlorophenylpiperazine (mCPP) have all been shown to modify appetite in both lean
      and obese humans, resulting in reduced caloric intake. Clinical studies
      demonstrate serotonergic drugs specifically reduce appetite prior to and
      following the consumption of fixed caloric loads, and cause a reduction in pre
      meal appetite and caloric intake at ad libitum meals. Weight loss in the obese
      has also been produced by treatment with both the serotonin precursor 5
      hydroxytryptophan and the preferential 5-HT2C receptor agonist mCPP.A new
      generation of 5-HT2C receptor selective agonists have been developed and at least
      one, lorcaserin (APD356), is currently undergoing clinical trials. In addition, 5
      HT6 receptor antagonists such as PRX-07034 and BVT74316 have been shown to
      potently reduce food intake and bodyweight gain in rodent models and have
      recently entered clinical trials. However, the role of the 5-HT6 receptor in the
      expression of appetite remains to be determined. The hope is that these drugs
      will not only be free of their predecessors' adverse effect profiles, but will
      also be equally or more effective at regulating appetite and controlling
      bodyweight.

PMID- 17209665
TI  - Ocular adverse effects associated with systemic medications : recognition and
      management.
AB  - This article reviews several retrospective case series and reported adverse
      events regarding common ocular adverse effects related to systemic therapy. It is
      not intended as a comprehensive summary of these well described adverse drug
      reactions, nor is it intended to cover the complete spectrum of all ocular
      adverse effects of systemic therapy. Many systemic drugs may produce ocular
      toxicity, including bisphosphonates, topiramate, vigabatrin, isotretinoin and
      other retinoids, amiodarone, ethambutol, chloroquine and hydroxychloroquine,
      tamoxifen, quetiapine, cyclo-oxygenase (COX)-2 inhibitors, erectile dysfunction
      agents and some herbal medications. For this review, the certainty of the adverse
      effect profile of each medication was evaluated according to the WHO Causality
      Assessment Guide.A certain relationship has been established for pamidronate and
      alendronate as causes of scleritis, uveitis, conjunctivitis and blurred vision.
      Topiramate has been established as adversely causing symptoms consistent with
      acute angle-closure glaucoma, typically bilateral. Vigabatrin has been shown to
      cause bilateral irreversible visual field defects attributed to underlying
      medication-induced retinal pathology. Isotretinoin should be considered in the
      differential diagnosis of any patient with pseudotumour cerebri. Patients taking
      amiodarone and hydroxychloroquine should be monitored and screened regularly for
      development of optic neuropathy and maculopathy, respectively. Sildenafil has
      been reported to cause several changes in visual perception and is a possible,
      not yet certain, cause of anterior ischaemic optic neuropathy. Patients taking
      tamoxifen should also be monitored for development of dose-dependent maculopathy
      and decreased colour vision. COX-2 inhibitors should be included in the
      differential diagnosis of reversible conjunctivitis. Several herbal medications
      including canthaxanthine, chamomile, datura, Echinacea purpurea, Ginkgo biloba
      and liquorice have also been associated with several ocular adverse effects. It
      is the role of all healthcare professionals to detect, treat and educate the
      public about adverse reactions to medications as they are an important health
      problem.

PMID- 17209666
TI  - Fixed-dose combination lercanidipine/enalapril.
AB  - Lercanidipine, a dihydropyridine calcium channel blocker, and enalapril, an ACE
      inhibitor, are established antihypertensive agents. A fixed-dose tablet
      formulation of lercanidipine/enalapril is approved in Germany for the treatment
      of hypertension in patients not responding to monotherapy.
      Lercanidipine/enalapril 10mg/10mg once daily significantly reduced sitting
      diastolic blood pressure and sitting systolic blood pressure, relative to
      lercanidipine 10mg once daily, in a 12-week, randomised, double-blind trial in
      patients with mild to moderate hypertension who had previously not responded to 4
      weeks' treatment with lercanidipine. In a similarly designed trial,
      lercanidipine/enalapril 10mg/20mg once daily was significantly more effective
      than enalapril 20mg once daily in hypertensive patients who had previously not
      responded to enalapril monotherapy. Fixed-dose lercanidipine/enalapril was
      generally well tolerated, with a tolerability profile similar to that of either
      of the individual drugs alone or placebo. Cough was reported in <or=5.2% and
      peripheral oedema in <or=1.5% of lercanidipine/enalapril recipients.

PMID- 17209669
TI  - Limaprost.
AB  - Limaprost, an alprostadil (prostaglandin E1) analogue, is a vasodilator that
      increases blood flow and inhibits platelet aggregation. The efficacy of oral
      limaprost was evaluated in adult Japanese patients in three randomised, double
      blind, 6-week trials. One study included patients with thromboangiitis obliterans
      and two trials included patients with lumbar spinal canal stenosis. Limaprost was
      generally well tolerated and serious adverse events were uncommon.
      THROMBOANGIITIS OBLITERANS: In a randomised, double-blind trial in Japanese
      patients primarily with thromboangiitis obliterans (n=136), there was no
      significant difference between patients receiving limaprost 30 microg/day and
      those receiving oral ticlopidine 500 microg/day in the improvement of ischaemic
      symptoms. LUMBAR SPINAL CANAL STENOSIS: Limaprost 15 microg/day was superior to
      limaprost 3 microg/day for overall drug usefulness and overall improvement from
      baseline to study end in a phase III trial in 146 patients with lumbar spinal
      canal stenosis. Assessment of overall improvement considered various objective
      symptoms (e.g. muscle strength, walking ability) and subjective symptoms (e.g.
      pain or numbness in extremities), while overall usefulness also considered safety
      issues. The efficacy of limaprost 15 microg/day was not significantly different
      from that of 30 microg/day, but tended to be better than that of 6 microg/day in
      a phase II trial in patients with lumbar spinal canal stenosis and normal
      straight leg raise test results. The optimal dosage of limaprost for this
      indication was therefore deemed to be 15 microg/day.

PMID- 17209674
TI  - The challenges of leadership in the modern world: introduction to the special
      issue.
AB  - This article surveys contemporary trends in leadership theory as well as its
      current status and the social context that has shaped the contours of leadership
      studies. Emphasis is placed on the urgent need for collaboration among social
      neuro-cognitive scientists in order to achieve an integrated theory, and the
      author points to promising leads for accomplishing this. He also asserts that the
      4 major threats to world stability are a nuclear/biological catastrophe, a world
      wide pandemic, tribalism, and the leadership of human institutions. Without
      exemplary leadership, solving the problems stemming from the first 3 threats will
      be impossible.

PMID- 17209672
TI  - Fenofibrate: a review of its use in primary dyslipidaemia, the metabolic syndrome
      and type 2 diabetes mellitus.
AB  - Fenofibrate is a fibric acid derivative indicated for use in the treatment of
      primary hypercholesterolaemia, mixed dyslipidaemia and hypertriglyceridaemia in
      adults who have not responded to nonpharmacological measures. Its lipid-modifying
      effects are mediated by activation of peroxisome proliferator-activated receptor
      alpha. Fenofibrate also has nonlipid (i.e. pleiotropic) effects (e.g. it reduces
      fibrinogen, C-reactive protein and uric acid levels and improves flow-mediated
      dilatation). Fenofibrate improves lipid levels (in particular triglyceride [TG]
      and high-density lipoprotein-cholesterol [HDL-C] levels) in patients with primary
      dyslipidaemia. Its lipid-lowering profile means that fenofibrate is particularly
      well suited for use in atherogenic dyslipidaemia (characterised by high TG
      levels, low HDL-C levels and small, dense low-density lipoprotein [LDL]
      particles), which is commonly seen in patients with the metabolic syndrome and
      type 2 diabetes mellitus. Indeed, fenofibrate improves the components of
      atherogenic dyslipidaemia in patients with these conditions, including a shift
      from small, dense LDL particles to larger, more buoyant LDL particles. Greater
      improvements in lipid levels are seen when fenofibrate is administered in
      combination with an HMG-CoA reductase inhibitor (statin) or in combination with
      ezetimibe, compared with monotherapy with these agents. In the DAIS study,
      fenofibrate significantly slowed the angiographic progression of focal coronary
      atherosclerosis in patients with type 2 diabetes. In terms of clinical outcomes,
      although no significant reduction in the risk of coronary events was seen with
      fenofibrate in the FIELD trial in patients with type 2 diabetes, treatment was
      associated with a significantly reduced risk of total cardiovascular disease
      (CVD) events, primarily through the prevention of non-fatal myocardial infarction
      and coronary revascularisation. Subgroup analyses revealed significant reductions
      in total CVD events and coronary heart disease events in patients with no
      previous CVD, suggesting a potential role for primary prevention with fenofibrate
      in patients with early type 2 diabetes. Improvements were also seen in
      microvascular outcomes with fenofibrate in the FIELD trial. Fenofibrate is
      generally well tolerated, both as monotherapy and when administered in
      combination with a statin. Combination therapy with fenofibrate plus a statin
      appears to be associated with a low risk of rhabdomyolysis; no cases of
      rhabdomyolysis were reported in patients receiving such therapy in the FIELD
      trial. Thus, fenofibrate is a valuable lipid-lowering agent, particularly in
      patients with atherogenic dyslipidaemia.

PMID- 17209675
TI  - Trait-based perspectives of leadership.
AB  - The trait-based perspective of leadership has a long but checkered history. Trait
      approaches dominated the initial decades of scientific leadership research.
      Later, they were disdained for their inability to offer clear distinctions
      between leaders and nonleaders and for their failure to account for situational
      variance in leadership behavior. Recently, driven by greater conceptual,
      methodological, and statistical sophistication, such approaches have again risen
      to prominence. However, their contributions are likely to remain limited unless
      leadership researchers who adopt this perspective address several fundamental
      issues. The author argues that combinations of traits and attributes, integrated
      in conceptually meaningful ways, are more likely to predict leadership than
      additive or independent contributions of several single traits. Furthermore, a
      defining core of these dominant leader trait patterns reflects a stable tendency
      to lead in different ways across disparate organizational domains. Finally, the
      author summarizes a multistage model that specifies some leader traits as having
      more distal influences on leadership processes and performance, whereas others
      have more proximal effects that are integrated with, and influenced by,
      situational parameters.

PMID- 17209676
TI  - The role of the situation in leadership.
AB  - Leadership depends on the situation. Few social scientists would dispute the
      validity of this statement. But the statement can be interpreted in many
      different ways, depending, at least in part, on what one means by leadership.
      This article begins with a definition of leadership and a brief description of 3
      historically important theories of leadership. The most recent of these,
      contingency theories, is argued to be most consistent with existing evidence and
      most relevant to professional practice. The Vroom, Yetton, and Jago contingency
      models of participation in decision making are described in depth, and their work
      provides the basis for identifying 3 distinct ways in which situational or
      contextual variables are relevant to both research on and the practice of
      leadership.

PMID- 17209677
TI  - Promoting more integrative strategies for leadership theory-building.
AB  - The agenda for theory and research in the field of leadership studies has evolved
      over the last 100 years from focuses on the internal dispositions associated with
      effective leaders to broader inquiries that include emphases on the cognitions,
      attributes, behaviors, and contexts in which leaders and followers are
      dynamically embedded and interact over time. Leadership theory and research has
      reached a point in its development at which it needs to move to the next level of
      integration--considering the dynamic interplay between leaders and followers,
      taking into account the prior, current, and emerging context--for continued
      progress to be made in advancing both the science and practice of leadership.

PMID- 17209678
TI  - A systems model of leadership: WICS.
AB  - This article reviews a systems model of leadership. According to the model,
      effective leadership is a synthesis of wisdom, creativity, and intelligence
      (WICS). It is in large part a decision about how to marshal and deploy these
      resources. One needs creativity to generate ideas, academic (analytical)
      intelligence to evaluate whether the ideas are good, practical intelligence to
      implement the ideas and persuade others of their worth, and wisdom to balance the
      interests of all stakeholders and to ensure that the actions of the leader seek a
      common good. The article relates the current model to other extant models of
      leadership.

PMID- 17209687
TI  - Grand theories of personality cannot be integrated.

PMID- 17209688
TI  - Personality theories facilitate integrating the five principles and deducing
      hypotheses for testing.

PMID- 17209689
TI  - Problems with McAdams and Pals's (2006) proposal of a framework for an
      integrative theory of personality.

PMID- 17209691
TI  - Meta-analysis of psychological interventions for chronic low back pain.
AB  - The purpose of this meta-analysis of randomized controlled trials was to evaluate
      the efficacy of psychological interventions for adults with noncancerous chronic
      low back pain (CLBP). The authors updated and expanded upon prior meta-analyses
      by using broad definitions of CLBP and psychological intervention, a broad data
      search strategy, and state-of-the-art data analysis techniques. All relevant
      controlled clinical trials meeting the inclusion criteria were identified
      primarily through a computer-aided literature search. Two independent reviewers
      screened abstracts and articles for inclusion criteria and extracted relevant
      data. Cohen's d effect sizes were calculated by using a random effects model.
      Outcomes included pain intensity, emotional functioning, physical functioning
      (pain interference or pain-specific disability, health-related quality of life),
      participant ratings of global improvement, health care utilization, health care
      provider visits, pain medications, and employment/disability compensation status.
      A total of 205 effect sizes from 22 studies were pooled in 34 analyses. Positive
      effects of psychological interventions, contrasted with various control groups,
      were noted for pain intensity, pain-related interference, health-related quality
      of life, and depression. Cognitive-behavioral and self-regulatory treatments were
      specifically found to be efficacious. Multidisciplinary approaches that included
      a psychological component, when compared with active control conditions, were
      also noted to have positive short-term effects on pain interference and positive
      long-term effects on return to work. The results demonstrated positive effects of
      psychological interventions for CLBP. The rigor of the methods used, as well as
      the results that reflect mild to moderate heterogeneity and minimal publication
      bias, suggest confidence in the conclusions of this review.

PMID- 17209692
TI  - Meta-analyses and systematic reviews of psychological treatments for chronic
      pain: relevance to an evidence-based practice.
AB  - As evidence-based practitioners become more reliant on systematic reviews to
      inform treatment, it becomes important to systematize reporting details as well
      as improve the quality of the primary studies that will later be incorporated
      into this secondary literature. In this article, the authors consider several
      specific factors that can serve this function in the area of chronic pain: (a)
      adhering to a standardized set of reporting standards; (b) measuring a
      standardized set of short- and long-term outcome variables; (c) providing
      information about individual differences; and (d) providing detailed, easily
      accessible documentation of the treatment program (or progams). The article also
      highlights ways that practitioners and researchers can collaborate on treatment
      outcome research, thereby improving the ability to discover and disseminate
      effective treatments for patients who suffer from chronic pain.

PMID- 17209693
TI  - Cardiac autonomic reactivity and recovery in predicting carotid atherosclerosis:
      the cardiovascular risk in young Finns study.
AB  - The present study examined the association of cardiac autonomic task-induced
      reactivity and recovery to preclinical atherosclerosis. Thirty-three men and 33
      women aged 24-39 years participated in the ongoing epidemiological Cardiovascular
      Risk in Young Finns study. The authors measured heart rate (HR), respiratory
      sinus arrhythmia (RSA), and preejection period (PEP) during the mental arithmetic
      and speech tasks in 1999. Carotid atherosclerosis was assessed by measuring the
      thickness of the common carotid artery intima-media complex (IMT) with ultrasound
      in 2001. Higher HR, RSA, and PEP reactivity were associated with lower IMT values
      even after adjusting for cardiovascular risk factors (lipid levels, obesity, and
      blood pressure). In addition, better HR recovery after the mental arithmetic task
      was associated with lower IMT values, and this association persisted after all
      adjustments. Thus, higher task-induced cardiac autonomic reactivity and better HR
      recovery were related to less preclinical atherosclerosis. The authors concluded
      that cardiac pattern of reactivity and quick recovery may be associated with
      better cardiovascular health, and therefore all reactivity occurring in
      challenging situations should not automatically be considered as potentially
      pathological.

PMID- 17209694
TI  - The influence of preferred coping style and cognitive strategy on laboratory
      induced pain.
AB  - OBJECTIVE: To evaluate the effects of matching an individual's coping style (low,
      mixed, or high monitoring) to an appropriate cognitive strategy (distraction or
      sensation monitoring) to improve pain management. DESIGN: This study used a split
      plot factorial design in a laboratory setting. MAIN OUTCOME MEASURES: Main
      outcomes were pain threshold, pain tolerance, pain intensity, pain affect, and
      anxiety. RESULTS: The results of the 2 x 3 x 3 (Experimental Condition x Coping
      Style x Trial) analysis of variance (ANOVA) interaction were significant for pain
      threshold scores, F(4, 178) = 2.95, p < .01. Low monitors in the matched
      distraction trial had higher pain threshold scores than during baseline, t(15) = 
      2.68, p = .017, and the mismatched sensation monitoring trial, t(15) = 2.80, p =
      .014. High monitors' pain threshold scores were higher than baseline only during
      the matched sensation monitoring trial, t(27) = -2.75, p = .010. The results of
      the 2 x 3 x 3 ANOVA interaction were not significant for pain tolerance scores;
      however, when the mixed monitors were excluded, the 3-way interaction was
      significant, F(2, 124) = 3.48, p < .05. The results were nonsignificant for pain
      intensity, pain affect, and anxiety. CONCLUSION: Results demonstrate that
      matching coping style to the appropriate cognitive strategy is important for
      improving pain threshold and pain tolerance; however, matching did not reduce
      pain intensity, pain affect, or anxiety. Future studies should explore the
      explanation for differential responses of high and low monitors and should test
      these hypotheses in a clinical setting.

PMID- 17209695
TI  - A transdisciplinary model integrating genetic, physiological, and psychological
      correlates of voluntary exercise.
AB  - OBJECTIVE: Physical inactivity contributes to as many as 250,000 premature deaths
      per year (R. R. Pate et al., 1995). The authors' objective was to test a
      transdisciplinary model of the ways in which genetic variants, physiological
      factors, and psychological factors are thought to influence exercise with 64
      healthy, regular exercisers. DESIGN: In a within-subjects design, psychological
      and physiological responses to exercise were compared with responses to a
      sedentary activity. MAIN OUTCOME MEASURES: The authors measured affective state,
      perceived exertion, heart rate, and temperature change in response to moderate
      exercise versus sedentary activity. They also quantified genotypes on a single
      nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene.
      RESULTS AND CONCLUSIONS: The data show a relation between increases in positive
      affective states and acute exercise behavior, as opposed to a sedentary control.
      The BDNF gene moderated the effect of exercise on mood, heart rate, and perceived
      exertion. Physiological factors were, in turn, related to mood response, and mood
      response was a significant correlate of motivation to exercise in the future and
      of current exercise behavior. The model has potential as a framework for the
      basic study of the genetic, physiological, and psychological processes involved
      with voluntary exercise and as a tool for the applied examination of tailored
      exercise interventions and their efficacy for different subsets of individuals.

PMID- 17209696
TI  - Age-associated predictors of medication adherence in HIV-positive adults: health
      beliefs, self-efficacy, and neurocognitive status.
AB  - OBJECTIVE: Although most agree that poor adherence to antiretrovirals is a common
      problem, relatively few factors have been shown to consistently predict treatment
      failure. In this study, a theoretical framework encompassing demographic
      characteristics, health beliefs/attitudes, treatment self-efficacy, and
      neurocognitive status was examined in relationship to highly active
      antiretroviral therapy adherence. DESIGN: Prospective, cross-sectional
      observational design. MAIN OUTCOME MEASURES: Neuropsychological test performance,
      health beliefs and attitudes, and medication adherence tracked over a 1-month
      period using electronic monitoring technology (Medication Event Monitoring System
      caps). RESULTS: The rate of poor adherence was twice as high among younger
      participants than with older participants (68% and 33%, respectively). Results of
      binary logistic regression revealed that low self-efficacy and lack of perceived
      treatment utility predicted poor adherence among younger individuals, whereas
      decreased levels of neurocognitive functioning remained the sole predictor of
      poor adherence among older participants. CONCLUSION: These data support
      components of the health beliefs model in predicting medication adherence among
      younger HIV-positive individuals. However, risk of adherence failure in those
      ages 50 years and older appears most related to neurocognitive status.

PMID- 17209697
TI  - Ethnic pride and self-control related to protective and risk factors: test of the
      theoretical model for the strong African American families program.
AB  - OBJECTIVE: To test a theoretical model of how ethnic pride and self-control are
      related to risk and protective factors. DESIGN: A community sample of 670 African
      American youth (mean age = 11.2 years) were interviewed in households. MAIN
      OUTCOME MEASURES: Measures of cigarette smoking, alcohol use, and sexual behavior
      (lifetime to past month). RESULTS: Structural modeling analyses indicated
      parenting was related to self-control and self-esteem, and racial socialization
      was related to ethnic pride. Self-control and self-esteem variables were related
      to levels of deviance-prone attitudes and to perceptions of engagers in, or
      abstainers from, substance use and sexual behavior. The proximal factors
      (behavioral willingness, resistance efficacy, and peer behavior) had substantial
      relations to the criterion variables. Participant gender and parental education
      also had several paths in the model. Results were generally similar for the 2
      outcome behaviors. CONCLUSIONS: In this population, self-esteem and self-control
      are related to parenting approaches and have pathways to attitudes and social
      perceptions that are significant factors for predisposing to, or protecting
      against, early involvement in substance use and sexual behavior.

PMID- 17209698
TI  - Effects of question format and collection mode on the accuracy of retrospective
      surveys of health risk behavior: a comparison with daily sexual activity diaries.
AB  - OBJECTIVE: To use prospective diaries to assess the effects of alternative survey
      question formats and data collection modes on the accuracy of retrospective self
      reports of sexual behavior for the same time period. DESIGN: Over a 3-month
      period, 493 adults completed and returned by mail daily diaries of their sexual
      activities. Participants then returned to complete a retrospective survey of
      their sexual activities during the same 3-month time period. Participants were
      randomized to 1 of 6 retrospective experimental survey conditions that
      represented the combinations of 2 question formats (in aggregate and by partner)
      and 3 collection modes (paper questionnaire, computer-assisted self-interview
      [CASI], and audio-enhanced CASI). MAIN OUTCOME MEASURES: Frequencies of sexual
      activities and condom use reported in surveys were compared with what
      participants had recorded in their prospective daily diaries. RESULTS: Relative
      to activity recorded in daily diaries, participants more often underreported than
      overreported (61% vs. 28%, p < .05) sexual behavior in retrospective surveys.
      Greater survey-to-diary consistency in reported behavior was achieved with by
      partner question format (p < .032) and CASI collection modes (p < .05) used in
      surveys. However, median rates of error in survey-to-diary comparisons of
      reported behavior were as high as 40%. CONCLUSION: Even after refinements in
      survey question format and use of CASI techniques, there remained substantial
      error in participants' retrospective reports of sexual practices. These error
      rates may be comparable to, or even larger than, the expected effect size of some
      intervention studies. Further research is needed to improve the accuracy of
      sexual behavior reports.

PMID- 17209699
TI  - Latent variable assessment of outcomes in a nurse-managed intervention to
      increase latent tuberculosis treatment completion in homeless adults.
AB  - OBJECTIVE: To assess predictors of latent tuberculosis infection (LTBI)
      completion by using structural equation modeling (SEM) among homeless adults, a
      group at great risk for LTBI and active tuberculosis (TB). LTBI therapy is
      effective in stemming the progression to active TB, yet treatment adherence among
      homeless persons is difficult to attain. DESIGN: By using SEM, the authors
      assessed predictors of LTBI completion among a sample of 494 homeless adults in
      Los Angeles, CA, who received either a nurse case-managed program (NCM) or a
      usual care program. MAIN OUTCOME MEASURES: Latent variables were created with the
      baseline variables of site type, age, intervention status, dissatisfaction with
      health care, depression, TB risk assessment, alcohol use, heroin or cocaine use,
      and TB knowledge. Outcome variables included many of the same baseline variables
      as well as treatment completion. RESULTS: LTBI treatment completion (100%
      adherence) was significantly and positively associated with participation in NCM,
      older age, and less heroin or cocaine use. NCM also predicted greater TB
      knowledge, greater ease of treatment, and more satisfaction with treatment (NCM
      completion rate = 64%, control rate = 42%). CONCLUSION: The culturally competent
      NCM program, combined with active tracking and incentives, was successful in a
      difficult-to-treat and highly transient population.

PMID- 17209700
TI  - How does coping help people resist lapses during smoking cessation?
AB  - OBJECTIVES: To determine whether types of coping strategies have differential
      effects on preventing lapses and lowering urge levels and to investigate
      mechanisms by which coping strategies prevent lapses during smoking cessation.
      DESIGN: Sixty-one respondents performed ecological momentary assessment using
      palm-top computers and tape recorders to report their coping strategies and urge
      levels before and after temptations to smoke. Multilevel linear regression models
      were used to compare the effects of individual strategy types with the average
      strategy. MAIN OUTCOME MEASURES: Lapses versus resisted temptations and changes
      in urge levels. RESULTS: Number of strategies significantly predicted resisting
      smoking and change in urge levels. Compared with the effect of the average
      strategy, movement/exercise was marginally worse at preventing lapses, and
      food/drink was marginally related to higher postcoping urge levels. CONCLUSION:
      Although using multiple coping strategies helps people resist the urge to smoke,
      no particular coping strategy works better than any other. Coping strategies
      prevent lapses by reducing high urge levels during temptations.

PMID- 17209701
TI  - Do induced moods really influence health perceptions?
AB  - OBJECTIVE: To determine whether induced mood alters health reports. DESIGN:
      Randomized experiments testing a) mood influence on two global self-rated health
      (SRH) assessments (Study 1; N = 168) and b) testing whether illness relevant
      thinking moderates the influence of induced negative mood on SRH and physical
      symptom reports (Study 2; N = 143). MAIN OUTCOME MEASURES: Two global SRH items.
      Results. Effect sizes for induced mood were near zero across both studies (r's =
      0.00-0.07). Aggregate analyses of induced mood studies showed a small adverse
      effect of induced negative mood on SRH, but these analyses masked roughly equal
      instances of better SRH among groups with worse mood. CONCLUSION: Published
      experimental research shows no consistent pattern of poorer SRH following
      negative mood induction in college-aged samples. Sample size and gender may
      account for variation in health ratings among induced mood groups.

PMID- 17209702
TI  - Migrant mental health: a model for indicators of mental health and health care
      consumption.
AB  - OBJECTIVE: This study explores the relationship between mental health and health
      care consumption among migrants in the Netherlands. DESIGN: Samples of the
      Turkish (n = 648), Moroccan (n = 102), and Surinamese (n = 311) populations in
      Amsterdam were examined. The study tested a hypothesized model of risk factors
      for psychiatric morbidity, indicators of well-being, and indicators of health
      care consumption. The model was specified on the basis of information from
      earlier research on the sample and literature on the topic. The model was tested
      and refined using structural equation modeling. MAIN OUTCOME MEASURES:
      Psychiatric morbidity and well-being measures were assessed with the CIDI 1.1 and
      MOS-sf-36 subscales, respectively. Health care consumption was assessed by the
      question "Have you ever consulted one or more of these professionals or health
      care facilities with respect to mental health problems or problems related to
      alcohol or drugs usage?" RESULTS: The primary result of this study was the
      confirmation that health care consumption among migrants is predicted by need and
      predisposition factors, such as health condition and sociodemographic
      characteristics. In addition, mental health care consumption of migrants is
      predicted by acculturation characteristics. This result suggests an effect of
      cultural and migrant-specific factors in help-seeking behavior and barriers to
      mental health care facilities. CONCLUSIONS: Findings confirm the existence of
      migrant-specific mechanisms in health care consumption. Mental health care
      professionals should be aware of these. However, ignoring common ground for
      interventions unnecessarily creates distance between migrant groups and between
      migrant and indigenous Dutch groups.

PMID- 17209703
TI  - The dieting dilemma in patients with newly diagnosed type 2 diabetes: does
      dietary restraint predict weight gain 4 years after diagnosis?
AB  - OBJECTIVE: To examine whether dieting--restriction of food intake for the purpose
      of weight control--suppresses or promotes excessive food intake and weight gain.
      DESIGN: A 4-year follow-up study of a dietary intervention in a sample of 97
      patients with newly diagnosed Type 2 diabetes. MAIN OUTCOME MEASURES: Weight
      gain, change in body mass index (measured weight in kilograms divided by measured
      height squared), and intake of energy, as measured with a food frequency
      questionnaire, were assessed in relation to dietary restraint and tendency to
      overeat (emotionally or externally induced overeating), as assessed with the
      Dutch Eating Behaviour Questionnaire. RESULTS: Tendency to overeat at diagnosis
      and not dietary restraint was associated with weight gain and intake of energy 4
      years after diagnosis. CONCLUSION: These findings suggest that the success of a
      dietary intervention can be predicted by a subject's tendency toward overeating.
      The possibility of matched treatment of obesity is discussed on the basis of the
      distinction between patients with a low versus a high tendency to overeat.

PMID- 17209704
TI  - Patterns of sedentary behavior among adolescents.
AB  - OBJECTIVE: Reducing certain sedentary behaviors (e.g., watching television, using
      a computer) can be an effective weight loss strategy for youth. Knowledge about
      whether behaviors cluster together could inform interventions. STUDY DESIGN:
      Estimates of time spent in 6 sedentary behaviors (watching television, talking on
      the telephone, using a computer, listening to music, doing homework, reading)
      were cluster analyzed for a sample of 878 adolescents (52% girls, mean age = 12.7
      years, 58% Caucasian). MAIN OUTCOME MEASURES: The clusters were based on the
      sedentary behaviors listed above and compared on environmental variables (e.g.,
      household rules), psychosocial variables (e.g., self-efficacy, enjoyment), and
      health behaviors (e.g., physical activity, diet). RESULTS: Four clusters emerged:
      low sedentary, medium sedentary, selective high sedentary, and high sedentary.
      Analyses revealed significant cluster differences for gender (p < .002), age (p <
      .002), body mass index (p < .001), physical activity (p < .01), and fiber intake
      (p < .01). CONCLUSIONS: Results suggest a limited number of distinct sedentary
      behavior patterns. Further study is needed to determine how interventions may use
      cluster membership to target segments of the adolescent population.

PMID- 17209705
TI  - Mechanisms by which childhood personality traits influence adult health status:
      educational attainment and healthy behaviors.
AB  - OBJECTIVE: The purpose of this study was to test a life span health behavior
      model in which educational attainment and health behaviors (eating habits,
      smoking, and physical activity) were hypothesized as mechanisms to account for
      relations between teacher ratings of childhood personality traits and self
      reported health status at midlife. DESIGN: The model was tested on 1,054 members
      of the Hawaii Personality and Health cohort, which is a population-based cohort
      participating in a longitudinal study of personality and health spanning 40 years
      from childhood to midlife. OUTCOME: Childhood Agreeableness, Conscientiousness,
      and Intellect-Imagination influenced adult health status indirectly through
      educational attainment, healthy eating habits, and smoking. Several direct
      effects of childhood traits on health behaviors and health status were also
      observed. CONCLUSION: The model extends past associations found between
      personality traits and health behaviors or health status by identifying a life
      course pathway based on the health behavior model through which early childhood
      traits influence adult health status. The additional direct effects of
      personality traits indicate that health behavior mechanisms may not provide a
      complete account of relations between personality and health.

PMID- 17209706
TI  - Rumination, fear, and cortisol: an in vivo study of interpersonal transgressions.
AB  - The authors sought to examine whether rumination about psychologically painful,
      though nontraumatic, interpersonal transgressions is associated with increased
      salivary cortisol. They measured salivary cortisol, rumination about a
      transgression, fear and anger regarding the transgressor, perceived painfulness
      of the transgression, and positive and negative mood in 115 undergraduates who
      had experienced an interpersonal transgression during the previous 7 days. They
      obtained measurements on as many as 5 occasions separated by approximately 14
      days each. On occasions when participants reported that they had been ruminating
      to a degree that was greater than was typical for them, they had higher levels of
      salivary cortisol than was typical for them. The rumination- cortisol association
      appeared to be mediated by fear of the transgressor. Rumination about even
      moderately painful but nontraumatic life events and associated emotions are
      related to biological changes that may subserve social goals such as avoiding
      social threats. Items from the rumination scale are appended.

PMID- 17209707
TI  - Needed: new concepts and methods in research on violence and its effects.

PMID- 17209709
TI  - Beyond trauma-focused psychiatric epidemiology: bridging research and practice
      with war-affected populations.
AB  - This article examines the centrality of trauma-focused psychiatric epidemiology
      (TFPE) in research with war-affected populations. The authors question the
      utility of the dominant focus on posttraumatic stress disorder and other
      disorders of Western psychiatry, and they identify a set of critical research
      foci related to mental health work with communities affected by political
      violence. Core assumptions of TFPE and its roots in logical positivism and the
      biomedical model of contemporary psychiatry are explored. The authors suggest
      that an alternative framework--social constructivism--can serve as a bridge
      between researchers and practitioners by helping to refocus research efforts in
      ways that are conceptually and methodologically more attuned to the needs of war
      affected communities and those working to address their mental health needs.

PMID- 17209710
TI  - The Afghan symptom checklist: a culturally grounded approach to mental health
      assessment in a conflict zone.
AB  - This article describes a methodology for developing culturally grounded
      assessment measures in conflict and postconflict situations. A mixed-method
      design was used in Kabul, Afghanistan, to identify local indicators of distress
      and develop the 22-item Afghan Symptom Checklist (ASCL). The ASCL contains
      several indigenous items and items familiar to Western mental health
      professionals. The ASCL was pilot tested and subsequently administered to 324
      adults in 8 districts of Kabul. It demonstrated excellent reliability (alpha=.93)
      and good construct validity, correlating strongly with a measure of exposure to
      war-related violence and loss (r=.70). Results of the survey indicate moderate
      levels of distress among Afghan men and markedly higher levels of distress and
      impaired functioning among women (and widows in particular).

PMID- 17209712
TI  - Delayed disclosure of alleged child abuse victims in Israel.
AB  - This study identifies characteristics of alleged child abuse victims that are
      associated with delayed disclosure of abuse. The database includes all alleged
      victims investigated in Israel between 1998 and 2004. Analyses suggest that most
      children delay disclosure and that delay is associated with type of abuse,
      child's age and gender, relationship to suspect and characteristics of abusive
      event.

PMID- 17209711
TI  - A gale force wind: meaning making by male survivors of childhood sexual abuse.
AB  - This in-depth qualitative study explores how 16 resilient male survivors of
      serious childhood sexual abuse, representing a range of racial, ethnic, and
      socioeconomic backgrounds, made meaning from their abuse experiences. Three main
      types of meaning making styles were identified in the narratives: meaning making
      through action, using cognitive strategies, and engaging spirituality. Meaning
      making through action included helping others and using creative expression to
      describe and process the abuse. Reasoning systems that helped survivors to
      understand why the abuse happened included developing a psychological framework
      for understanding the abuser or the role of the self in the abuse, using a
      sociocultural explanation, or developing a philosophical view. A few men made
      meaning through their spirituality. Meaning making styles seem to be related to
      experiences with therapy; the more experience these men had had with specialized
      trauma therapy, the more likely they were to make meaning by attempting to
      understand their perpetrators. In this study, men of color, regardless of
      socioeconomic class, were less likely than Caucasian men to have received
      specialized trauma therapy.

PMID- 17209713
TI  - The effects of trauma on intimate relationships: a qualitative study with
      clinical couples.
AB  - Research has traditionally focused on the development of symptoms in those who
      experienced trauma directly but has overlooked the impact of trauma on victims'
      families. In recent years, researchers and clinicians have begun to examine how
      individual exposure to traumatic events affects the spouses or partners,
      children, and professional helpers of trauma survivors. The current study
      examines qualitative interview data from 17 individuals, analyzed using a
      retroductive methodology to identify how intimate relationships are affected when
      there is a history of trauma exposure. The following primary themes were
      identified: increased communication, decreased communication, increased
      cohesion/connection, decreased cohesion/connection, increased understanding,
      decreased understanding, sexual intimacy problems, symptoms of relationship
      distress, support from partner, and relationship resources. Areas for future
      research and clinical implications are identified.

PMID- 17209714
TI  - In their own words: trauma and substance abuse in the lives of formerly homeless
      women with serious mental illness.
AB  - In-depth interviews were conducted with 13 formerly homeless mentally ill women
      to capture their individual life trajectories of mental illness, substance abuse,
      and trauma in their own words. Cross-case analyses produced 5 themes: (a)
      betrayals of trust, (b) graphic or gratuitous nature of traumatic events, (c)
      anxiety about leaving their immediate surroundings (including attending group
      treatment programs), (d) desire for one's own space, and (e) gender-related
      status loss and stigmatization. Findings suggest formerly homeless mentally ill
      women need (and want) autonomy, protection from further victimization, and
      assistance in restoring status and devalued identity. Avenues for intervention
      include enhanced provider training, addressing experiences of betrayal and
      trauma, and more focused attention to current symptoms rather than previous
      diagnoses.

PMID- 17209715
TI  - Profile of children investigated for sexual abuse: association with
      psychopathology symptoms and services.
AB  - Sexually abused children may have poor mental health because of their
      victimization as well as preexisting or co-occurring family problems. However,
      few studies consider psychopathology in relation to both abuse and other family
      experiences. This study uses data from the National Survey of Child and
      Adolescent Well-Being (NSCAW) to create latent subgroups of 553 children
      investigated for sexual abuse. The study investigates children's psychological
      symptoms and child welfare service (CWS) patterns to understand how children's
      needs relate to mental health services. Analyses were conducted by child age: 3
      7, 8-11, and 12-14. Factor mixture modeling and regression analyses were used.
      Results show meaningful subgroups of children that relate to different symptom
      patterns. Among 3- to 7-year-olds, behavioral symptoms are associated with
      caregiver domestic violence and mental illness. Among 8- to 11-year-olds,
      depressive symptoms are associated with severe abuse and multiple family
      problems, whereas posttraumatic stress is associated with chronic, unresolved
      abuse. Although many children received mental health services, services are not
      well matched to children's needs--the substantiation status of the abuse explains
      services. Implications for CWS and mental health services are discussed.

PMID- 17209716
TI  - Integrating exposure therapy and analytic therapy in trauma treatment.
AB  - Analytic therapy and Exposure Therapy come out of contending and, at times,
      contentious traditions in psychotherapy. They can, however, work together to
      better trauma treatment. Exposure Therapy is enhanced by close attention to
      individual psychodynamics. Analytic therapy can draw upon the rich narratives of
      Exposure work to deepen analytic inquiry.

PMID- 17209717
TI  - The full-frame approach: a new response to marginalized women left behind by
      specialized services.
AB  - Increasing emphasis on specialization in social and mental health services leaves
      these systems largely unable to attend to marginalized women's complex needs,
      despite new models designed to ameliorate specialization's impact. In this
      article, the authors describe how inattention to these women's contexts leaves
      them ill-served and leaves programs struggling. The authors articulate a new
      framework of principles and practices that privileges context and community, and
      describe two programs that use this "Full-Frame Approach." The authors contend
      that systemic recognition of full-frame programs as a strategic counterbalance to
      specialization is a vital component of helping marginalized people and
      communities move to new levels of health and cohesion.

PMID- 17209718
TI  - Effects of parenting style on personal and social variables for Asian
      adolescents.
AB  - Impact of perceived parenting style on adolescents' self-reliance, interpersonal
      relations, sense of inadequacy, and attitude to school, after controlling for
      effects of adolescents' self-esteem, was examined in a sample of 548 Asian
      adolescents. Fathers' perceived parenting style was significantly associated with
      adolescents' sense of inadequacy for the entire sample as well as for Chinese
      adolescents. Fathers' perceived parenting style was also significantly associated
      with Malay adolescents' self-reliance. Mothers' perceived parenting style was
      significant only for Malay adolescents' attitude to school. The meaning and
      consequences of parenting styles, in particular, the authoritarian parenting
      style, and the differential impact of paternal parenting style versus maternal
      parenting style on adolescent outcomes in an Asian context will be discussed.
      Implications for educators and mental health practitioners working with
      adolescents and their families will also be explored.

PMID- 17209719
TI  - Sex role ideology among East Asian immigrants in the United States.
AB  - Although sex role ideology (i.e., beliefs about the proper roles for men and
      women) is linked with self-definition and male-female interactions, researchers
      have rarely examined such beliefs among U.S. immigrants. This study examined the
      cultural (ethnic identity, self-construal) and demographic (gender, age, years in
      United States) correlates of sex role ideology among 170 (88 male, 82 female)
      East Asian immigrants using psychometrically established measures. Male
      participants who endorsed ethnic identity and interdependent self-construal were
      more likely to report traditional sex roles; female participants who lived for a
      longer period of time in the United States and who endorsed independent self
      construal were more likely to report sex role equality. Clinicians should
      consider assessing sex role ideology to reduce the likelihood of stereotyping
      their immigrant clients.

PMID- 17209720
TI  - Correlates of change in student reported parent involvement in schooling: a new
      look at the National Education Longitudinal Study of 1988.
AB  - Using a subsample (2174 students, 174 schools) from the National Education
      Longitudinal Study of 1988 (NELS), this study drew on Eccles and Harold's (1996)
      framework of parent involvement in schooling to estimate the relative influence
      of key child, family, and school characteristics on change in three types of
      student-reported parent involvement in schooling between eighth and tenth grades:
      home communication about school, monitoring, and direct interactions with
      schools. It also examines relationships between changes in involvement, change in
      grade point average (GPA), and dropout. Overall, measured school effects
      accounted for a small proportion of the variation in changes in home
      communication and direct parent interactions with schools. Sustained home
      communication related to higher grades and lower likelihood of dropout, although
      the size of effects was small.

PMID- 17209721
TI  - Integrating pediatric obesity treatment into clinical practice.
AB  - Childhood obesity has reached epidemic proportions in the United States and other
      industrialized nations. Despite the significant psychosocial consequences, mental
      health professionals have been reluctant to provide direct treatment for these
      children and their parents. The author proposes a practice model for agency,
      clinic, and private settings, with the mental health practitioner as primary
      clinician. On the basis of intervention research methodology, the model presents
      consensus generalizations and clinical applications for evaluation and treatment.
      A typology of diagnostic profiles with corresponding strategies for combining
      diet, activity, and mental health interventions is included.

PMID- 17209722
TI  - Changes in caregiving satisfaction and information needs among relatives of
      adults with mental illness: results of a randomized evaluation of a family-led
      education intervention.
AB  - The authors examined changes in caregiving satisfaction and information needs
      among 462 relatives of individuals with mental illness who participated in a
      study of a family-led education course, the Journey of Hope (JOH). Participants
      were randomly assigned to receive JOH or to a control group waiting list and
      followed for 9 months. General linear model repeated measures analysis of
      variance found that, compared with the control group, the intervention group
      showed significant improvement in caregiving satisfaction and information needs
      following course completion and maintained these gains for another 6 months.
      Education and support from other family members in the form of a structured
      course is effective in meeting the caregiving needs of relatives of persons with
      mental illness.

PMID- 17209723
TI  - Social skills and behavior problems of urban, African American preschoolers: role
      of parenting practices, family conflict, and maternal depression.
AB  - This study examined the role of parenting, family routines, family conflict, and
      maternal depression in predicting the social skills and behavior problems of low
      income African American preschoolers. A sample of 184 African American mothers of
      Head Start children completed participant and child measures in a structured
      interview. Results of regression analyses revealed that mothers who utilized more
      positive parenting practices and engaged in more family routines had children who
      displayed higher levels of total prosocial skills. Positive parenting and lower
      levels of maternal depressive symptoms were predictive of fewer externalizing and
      internalizing child behavior problems. Lower family conflict was linked with
      fewer externalizing problems. Implications of the study for future research and
      intervention are discussed.

PMID- 17209724
TI  - Maternal self-efficacy and associated parenting cognitions among mothers of
      children with autism.
AB  - Feelings of competency in the parental role, termed parenting self-efficacy, have
      been associated with well-being and positive parenting outcomes. Given the unique
      stresses inherent in raising a child with autism, parents may find it challenging
      to maintain a positive sense of well-being and self-efficacy. Study aims were to
      investigate associations between maternal self-efficacy and parenting cognitions
      among mothers of children with autism. Mothers (n = 170) completed questionnaires
      on paper or via the Internet. In a hierarchical linear regression, depression,
      parenting stress, agency, and guilt each accounted for unique variance in
      maternal self-efficacy when controlling for time since diagnosis and the presence
      of a second child with a disability. Autism knowledge was not associated with
      parenting self-efficacy. Self-efficacy appears to be associated with well-being,
      agency, and feelings of guilt among mothers of children with autism. Parent- and
      family-based interventions designed to support parental well-being and focusing
      on parenting cognitions may enhance parenting self-efficacy.

PMID- 17209725
TI  - The relation of phase noise and luminance contrast to overt attention in complex
      visual stimuli.
AB  - Models of attention are typically based on difference maps in low-level features
      but neglect higher order stimulus structure. To what extent does higher order
      statistics affect human attention in natural stimuli? We recorded eye movements
      while observers viewed unmodified and modified images of natural scenes.
      Modifications included contrast modulations (resulting in changes to first- and
      second-order statistics), as well as the addition of noise to the Fourier phase
      (resulting in changes to higher order statistics). We have the following
      findings: (1) Subjects' interpretation of a stimulus as a "natural" depiction of
      an outdoor scene depends on higher order statistics in a highly nonlinear,
      categorical fashion. (2) Confirming previous findings, contrast is elevated at
      fixated locations for a variety of stimulus categories. In addition, we find that
      the size of this elevation depends on higher order statistics and reduces with
      increasing phase noise. (3) Global modulations of contrast bias eye position
      toward high contrasts, consistent with a linear effect of contrast on fixation
      probability. This bias is independent of phase noise. (4) Small patches of
      locally decreased contrast repel eye position less than large patches of the same
      aggregate area, irrespective of phase noise. Our findings provide evidence that
      deviations from surrounding statistics, rather than contrast per se, underlie the
      well-established relation of contrast to fixation.

PMID- 17209726
TI  - A cortical pooling model of spatial summation for perimetric stimuli.
AB  - Contemporary models of perimetric sensitivity assume probability summation of
      retinal ganglion cell sensitivities, ignoring cortical processing. To assess the
      role of cortical processing in perimetric spatial summation, we used a common
      form of multiple-mechanism spatial vision model in which the stimulus is sampled
      by receptive fields analogous to those of simple cells in primary visual cortex.
      Psychophysical threshold was computed by probability summation across the
      receptive fields. When the receptive fields were nonoriented (like ganglion
      cells), the spatial summation function had a large nonmonotonic transitional
      region that was inconsistent with perimetric spatial summation data. When the
      receptive fields were orientation tuned (like cortical cells), the model was able
      to give good fits to perimetric spatial summation data. The predictions of the
      model were evaluated with a masking study, in which noise masks either enlarged
      the critical area or changed the shape of the spatial summation functions. We
      conclude that cortical pooling by multiple spatial mechanisms can account for
      perimetric spatial summation, whereas probability summation across ganglion cells
      cannot.

PMID- 17209727
TI  - Retinal image shifts, but not eye movements per se, cause alternations in
      awareness during binocular rivalry.
AB  - Particularly promising studies on visual awareness exploit a generally used
      perceptual bistability phenomenon, "binocular rivalry"--in which the two eyes'
      images alternately dominate--because it can dissociate the visual input from the
      perceptual output. To successfully study awareness, it is crucial to know the
      extent to which eye movements alter the input. Although there is convincing
      evidence that perceptual alternations can occur without eye movements, the
      literature on their exact role is mixed. Moreover, recent work has demonstrated
      that eye movements, first, correlate positively with perceptual alternations in
      binocular rivalry, and second, often accompany covert attention shifts (that were
      previously thought to be purely mental). Here, we asked whether eye movements
      cause perceptual alternations, and if so, whether it is either the execution of
      the eye movement or the resulting retinal image change that causes the
      alternation. Subjects viewed repetitive line patterns, enabling a distinction of
      saccades that did produce foveal image changes from those that did not. Subjects
      reported binocular rivalry alternations. We found that, although a saccade is not
      essential to initiate percept changes, the foveal image change resulting from a
      (micro)saccade is a deciding factor for percept dominance. We conclude that the
      foveal image must change to have a saccade cause a change in awareness. This
      sheds new light on the interaction between spatial attention shifts and
      perceptual alternations.

PMID- 17209728
TI  - Top-down attention selection is fine grained.
AB  - Although much is known about the sources and modulatory effects of top-down
      attentional signals, the information capacity of these signals is less known.
      Here, we investigate the granularity of top-down attentional signals. Previous
      theories in psychophysics have provided conflicting evidence on whether top-down
      guidance is coarse grained (i.e., one gain control term per feature dimension) or
      fine grained (i.e., multiple gain control terms per dimension). We resolve the
      conflict by designing new experiments that disentangle top-down from bottom-up
      contributions, thereby avoiding confounds existing in previous studies. The
      results of our eye-tracking experiments show that subjects can selectively
      saccade to items belonging to the relevant feature interval compared with
      irrelevant intervals within a dimension. This suggests that top-down signals can
      specify not only the relevant feature dimension but also the relevant feature
      interval within a dimension. We conclude that top-down signals are fine grained
      and can specify multiple gain control terms per dimension.

PMID- 17209729
TI  - Human cone light adaptation: from behavioral measurements to molecular
      mechanisms.
AB  - The ability of the cone visual system to regulate its sensitivity from twilight
      to bright sunlight is an extraordinary feat of biology. Here, we investigate the
      changes in visual processing that accompany cone light adaptation over a 5 log10
      unit intensity range by combining measures of temporal sensitivity made in one
      eye with measures of the temporal delay between the two eyes in different states
      of adaptation. This combination of techniques, which provides more complete
      information than has been available before, leads to a simple model of steady
      state light adaptation. At high light levels, visual sensitivity is maintained
      mainly by photopigment bleaching. At low-to-moderate light levels, it is
      maintained by trading unwanted sensitivity for speed and by an additional process
      that paradoxically increases the overall sensitivity as the light level rises.
      Each stage of the model can be linked to molecular mechanisms within the
      photoreceptor: The speeding up can be linked to faster rates of decay of
      activated molecules; the paradoxical sensitivity increases can be linked to
      faster rates of molecular resynthesis and to changes in channel sensitivity; and
      the sensitivity decreases can be linked to bleaching. Together, these mechanisms
      act to maintain the cone visual system in an optimal operating range and to
      protect it from overload.

PMID- 17209730
TI  - Stereomotion suppression and the perception of speed: accuracy and precision as a
      function of 3D trajectory.
AB  - The precision and accuracy of speed discrimination performance for stereomotion
      stimuli were assessed for several receding 3D trajectories confined to the
      horizontal meridian. It has previously been demonstrated in a variety of tasks
      that detection thresholds are substantially higher when subjects observe a
      stereomotion stimulus than when simply viewing one of its component monocular
      half-images--a phenomenon known as stereomotion suppression (C. W. Tyler, 1971).
      Using monocularly visible motion in depth targets, we found mean speed
      discrimination thresholds to be higher for stereomotion, compared with monocular
      lateral speed discrimination thresholds for equivalent stimuli, demonstrating a
      disadvantage for binocular viewing in the case of speed discrimination as well.
      Furthermore, speed discrimination thresholds for motion in depth were not
      systematically affected by trajectory angle; hence, the disadvantage of binocular
      viewing persists even when there are concurrent changes in binocular visual
      direction. Lastly, there was a tendency for oblique trajectories of stereomotion
      to be perceived as faster than equally rapid motion receding directly away from
      the subject along the midline. Our data, in addition to earlier stereomotion
      suppression observations, are consistent with a stereomotion system that takes a
      noisy, weighted difference of the stimulus velocities in the two eyes to compute
      motion in depth.

PMID- 17209731
TI  - Binocular contrast vision at and above threshold.
AB  - A fundamental problem for any visual system with binocular overlap is the
      combination of information from the two eyes. Electrophysiology shows that
      binocular integration of luminance contrast occurs early in visual cortex, but a
      specific systems architecture has not been established for human vision. Here, we
      address this by performing binocular summation and monocular, binocular, and
      dichoptic masking experiments for horizontal 1 cycle per degree test and masking
      gratings. These data reject three previously published proposals, each of which
      predict too little binocular summation and insufficient dichoptic facilitation.
      However, a simple development of one of the rejected models (the twin summation
      model) and a completely new model (the two-stage model) provide very good fits to
      the data. Two features common to both models are gently accelerating (almost
      linear) contrast transduction prior to binocular summation and suppressive ocular
      interactions that contribute to contrast gain control. With all model parameters
      fixed, both models correctly predict (1) systematic variation in psychometric
      slopes, (2) dichoptic contrast matching, and (3) high levels of binocular
      summation for various levels of binocular pedestal contrast. A review of evidence
      from elsewhere leads us to favor the two-stage model.

PMID- 17209732
TI  - The time course of binocular rivalry reveals a fundamental role of noise.
AB  - When our two eyes view incongruent images, we experience binocular rivalry: An
      ongoing cycle of dominance periods of either image and transition periods when
      both are visible. Two key forces underlying this process are adaptation of and
      inhibition between the images' neural representations. Models based on these
      factors meet the constraints posed by data on dominance periods, but these are
      not very stringent. We extensively studied contrast dependence of dominance and
      transition durations and that of the occurrence of return transitions: Occasions
      when an eye loses and regains dominance without intervening dominance of the
      other eye. We found that dominance durations and the incidence of return
      transitions depend similarly on contrast; transition durations show a different
      dependence. Regarding dominance durations, we show that the widely accepted rule
      known as Levelt's second proposition is only valid in a limited contrast range;
      outside this range, the opposite of the proposition is true. Our data refute
      current models, based solely on adaptation and inhibition, as these cannot
      explain the long and reversible transitions that we find. These features indicate
      that noise is a crucial force in rivalry, frequently dominating the deterministic
      forces.

PMID- 17209733
TI  - Spatial scale of stereomotion speed processing.
AB  - To examine the spatial scale of the mechanisms supporting the perception of
      motion in depth defined by binocular cues, we measured stereomotion speed
      discrimination thresholds as a function of stimulus size using a two-interval
      speed comparison task. Stimuli were either random dot stereogram (RDS) bars
      featuring both the changing disparity (CD) and the interocular velocity
      difference (IOVD) cues to motion in depth or dynamic random dot stereogram (DRDS)
      bars featuring the CD cue alone. Monocular speed discrimination performance was
      also assessed, using half-images of the RDS stimulus. In addition, subjects'
      stereoacuity for stationary versions of the binocular stimuli was measured.
      Stimuli ranged in vertical extent from 1.25 to 40 min. Sensitivity to speed
      differences was strongly related to stimulus height for DRDS stimuli. Performance
      decreased rapidly as stimulus size was reduced, becoming nearly random for
      heights below 5 min. However, for RDS stimuli, speed discrimination performance
      declined with reductions in stimulus size at a far slower rate, providing
      superior performance at every stimulus size used. Monocular performance was
      superior still for the majority of subjects, yet showed a similar rate of decline
      to binocular RDS stimuli. We conclude that the spatial resolution of the CD
      mechanism and its static disparity inputs is, on average, nearly nine times more
      coarse than the IOVD system and its monocular motion inputs. Static stereoacuity
      controls show that this finding cannot be explained by differences in the
      disparity signals available in our RDS and DRDS stimuli.

PMID- 17209735
TI  - The fate of object features during perisaccadic mislocalization.
AB  - Visual objects flashed before a saccade appear compressed toward the saccade
      target. Simultaneously flashed objects merge perceptually into one. To better
      understand cortical interactions in perisaccadic processing, we study the
      perception of features of mislocalized objects. We report four new findings:
      First, when multiple objects of different colors are compressed onto a single
      position, their color attributes remain distinguishable. Second, color attributes
      of objects compressed onto the same position compete for access to visual
      awareness. Third, objects presaccadically mislocalized onto a static background
      of identical color and luminance appear visible on top of that background. Object
      shape can be determined. Fourth, objects flashed during a saccade become
      invisible when a larger object is present at the mislocalized position. Thus,
      perisaccadic mislocalization affects the position of objects but retains other
      object features. Mislocalization must either occur in parallel to color and shape
      processing or at late stages of the visual pathway.

PMID- 17209734
TI  - Bayesian model of human color constancy.
AB  - Vision is difficult because images are ambiguous about the structure of the
      world. For object color, the ambiguity arises because the same object reflects a
      different spectrum to the eye under different illuminations. Human vision
      typically does a good job of resolving this ambiguity-an ability known as color
      constancy. The past 20 years have seen an explosion of work on color constancy,
      with advances in both experimental methods and computational algorithms. Here, we
      connect these two lines of research by developing a quantitative model of human
      color constancy. The model includes an explicit link between psychophysical data
      and illuminant estimates obtained via a Bayesian algorithm. The model is fit to
      the data through a parameterization of the prior distribution of illuminant
      spectral properties. The fit to the data is good, and the derived prior provides
      a succinct description of human performance.

PMID- 17209736
TI  - Neural correlates of the visual vertical meridian asymmetry.
AB  - Human visual performance is better below than above fixation along the vertical
      meridian-a phenomenon we refer to as vertical meridian asymmetry (VMA). Here, we
      used fMRI to investigate the neural correlates of the VMA. We presented stimuli
      of two possible sizes and spatial frequencies on the horizontal and vertical
      meridians and analyzed the fMRI data in subregions of early visual cortex (V1/V2)
      that corresponded retinotopically to the stimulus locations. Asymmetries in both
      the spatial extent and amplitude of the fMRI measurements correlated with the
      behavioral VMA. These results demonstrate that the VMA has a neural basis at the
      earliest stages of cortical visual processing and imply that visual performance
      is limited by the pooled sensory responses of large populations of neurons in the
      visual cortex.

PMID- 17209737
TI  - Spatial four-alternative forced-choice method is the preferred psychophysical
      method for naive observers.
AB  - H. R. Blackwell (1952) investigated the influence of different psychophysical
      methods and procedures on detection thresholds. He found that the temporal two
      interval forced-choice method (2-IFC) combined with feedback, blocked constant
      stimulus presentation with few different stimulus intensities, and highly trained
      observers resulted in the "best" threshold estimates. This recommendation is in
      current practice in many psychophysical laboratories and has entered the
      psychophysicists' "folk wisdom" of how to run proper psychophysical experiments.
      However, Blackwell's recommendations explicitly require experienced observers,
      whereas many psychophysical studies, particularly with children or within a
      clinical setting, are performed with naive observers. In a series of
      psychophysical experiments, we find a striking and consistent discrepancy between
      naive observers' behavior and that reported for experienced observers by
      Blackwell: Naive observers show the "best" threshold estimates for the spatial
      four-alternative forced-choice method (4-AFC) and the worst for the commonly
      employed temporal 2-IFC. We repeated our study with a highly experienced
      psychophysical observer, and he replicated Blackwell's findings exactly, thus
      suggesting that it is indeed the difference in psychophysical experience that
      causes the discrepancy between our findings and those of Blackwell. In addition,
      we explore the efficiency of different methods and show 4-AFC to be more than 3.5
      times more efficient than 2-IFC under realistic conditions. While we have found
      that 4-AFC consistently gives lower thresholds than 2-IFC in detection tasks, we
      have found the opposite for discrimination tasks. This discrepancy suggests that
      there are large extrasensory influences on thresholds--sensory memory for IFC
      methods and spatial attention for spatial forced-choice methods--that are
      critical but, alas, not part of theoretical approaches to psychophysics such as
      signal detection theory.

PMID- 17209738
TI  - Does depth perception require vertical-disparity detectors?
AB  - Stereo depth perception depends on the fact that objects project to different
      positions in the two eyes. Because our eyes are offset horizontally, these
      retinal disparities are mainly horizontal, and horizontal disparity suffices to
      give an impression of depth. However, depending on eye position, there may also
      be small vertical disparities. These are significant because, given both vertical
      and horizontal disparities, the brain can deduce eye position from purely retinal
      information and, hence, derive the position of objects in space. However, we show
      here that, to achieve this, the brain need measure only the magnitude of vertical
      disparity; for physically possible stimuli, the sign then follows from the stereo
      geometry. The magnitude of vertical disparity--and hence eye position--can be
      deduced from the response of purely horizontal-disparity sensors because vertical
      disparity moves corresponding features off the receptive fields, reducing the
      effective binocular correlation. As proof, we demonstrate an algorithm that can
      accurately reconstruct gaze and vergence angles from the population activity of
      pure horizontal-disparity sensors and show that it is subject to the induced
      effect. Given that disparities experienced during natural viewing are
      overwhelmingly horizontal and that eye position measures require only horizontal
      disparity sensors, this work raises two questions: Does the brain in fact contain
      sensors tuned to nonzero vertical disparities, and if so, why?

PMID- 17209739
TI  - Where are kin recognition signals in the human face?
AB  - We report two experiments that aimed to determine where in the face the cues that
      signal kinship fall. In both experiments, participants were shown 30 pairs of
      photographs of children's faces. Half of the pairs portrayed siblings and half
      did not. The 220 participants were asked to judge whether each pair of
      photographs portrayed siblings. We measured the effect on kin recognition
      performance of masks that covered the upper half or the lower half of the face
      (Experiment 1) and the eye region or the mouth region (Experiment 2). In
      Experiment 1, we found that the signal detection estimate of performance d'
      decreased only 5.3% (ns) when the lower face was masked but by more than 65% when
      the upper face was masked. We tested whether the combination of kinship
      information from the two halves of the face can be treated as optimal combination
      of independent cues and found that it could be. In Experiment 2, we found that
      masking the eye region led to only a 20% reduction (ns) in performance whereas
      masking the mouth region led to a nonsignificant increase in performance. We also
      found that the eye region contains only slightly more information about kinship
      than the upper half of the face outside of the eye region.

PMID- 17209740
TI  - Is the ability to identify deviations in multiple trajectories compromised by
      amblyopia?
AB  - Amblyopia results in a severe loss of positional information and in the ability
      to accurately enumerate objects (V. Sharma, D. M. Levi, & S. A. Klein, 2000). In
      this study, we asked whether amblyopia also disrupts the ability to track a near
      threshold change in the trajectory of a single target amongst multiple similar
      potential targets. In the first experiment, we examined the precision for
      detecting a deviation in the linear motion trajectory of a dot by measuring
      deviation thresholds as a function of the number of moving trajectories (T). As
      in normal observers, we found that in both eyes of amblyopes, threshold increases
      steeply as T increases from 1 to 4. Surprisingly, for T = 1-4, thresholds were
      essentially identical in both eyes of the amblyopes and were similar to those of
      normal observers. In a second experiment, we measured the precision for detecting
      a deviation in the orientation of a static, bilinear "trajectory" by again
      measuring deviation thresholds (i.e., angle discrimination) as a function of the
      number of oriented line "trajectories" (T). Relative to the nonamblyopic eye,
      amblyopes show a marked threshold elevation for a static target when T = 1.
      However, thresholds increased with T with approximately the same slope as in
      their preferred eye and in the eyes of the normal controls. We conclude that
      while amblyopia disrupts static angle discrimination, amblyopic dynamic deviation
      detection thresholds are normal or very nearly so.

PMID- 17209741
TI  - Discrete color filling beyond luminance gaps along perceptual surfaces.
AB  - Perceived color at a point in space is not determined simply by the color
      directly stimulating the corresponding retinal position. Surface color is
      informed by flanking edge signals, which also serve to inhibit the intrusion of
      signals from neighboring surfaces. Spatially continuous local interactions among
      color and luminance signals have been implicated in a propagation process often
      referred to as filling-in. Here, we report a phenomenon of discrete color filling
      whereby color jumps over luminance gaps filling into disconnected regions of the
      stimulus. This color filling is found to be blocked at boundaries defined by
      texture. The color filling is also highly specific to the elements belonging to a
      common perceptual surface, even when multiple surfaces are transparently
      overlaid. Our results indicate that color filling can be governed by a host of
      visual cues outside the realm of first-order color and brightness, via their
      impact on perceptual surface segmentation and segregation.

PMID- 17209742
TI  - Explaining the footsteps, belly dancer, Wenceslas, and kickback illusions.
AB  - The footsteps illusion (FI) demonstrates that an object's background can have a
      profound effect on the object's perceived speed. This illusion consists of a
      yellow bar and a blue bar that move over a black-and-white, striped background.
      Although the bars move at a constant rate, they appear to repeatedly accelerate
      and decelerate in antiphase with each other. Previously, this illusion has been
      explained in terms of the variations in contrast at the leading and trailing
      edges of the bars that occur as the bars traverse the striped background. Here,
      we show that this explanation is inadequate and instead propose that for each
      bar, the bar's leading edge, trailing edge, lateral edges, and the surrounding
      background edges all contribute to the bar's perceived speed and that the degree
      to which each edge contributes to the motion percept is determined by that edge's
      contrast. We show that this theory can explain all the data on the FI as well as
      the belly dancer and Wenceslas illusions. We conclude by presenting a new
      illusion, the kickback illusion, which, although geometrically similar to the FI,
      is mediated by a different mechanism, namely, reverse phi motion.

PMID- 17209743
TI  - The speed of visual attention: what time is it?
AB  - The time course of visual attention has been studied using a number of
      experimental designs. Here, we present a refined version of a technique first
      used by Wundt more than a century ago and demonstrate it as an effective method
      to measure the speed of visual attention. The method generates precise and robust
      data quickly and is flexible enough to be adapted into a variety of established
      paradigms. In the experiment, participants view an array of moving clocks and
      report the time on a target clock, which was indicated by a peripheral or central
      cue. We found latencies of around 140 ms when the target was cued peripherally
      and latencies of around 240 ms when the target was cued centrally. These values
      are in good agreement with previous literature and support the validity of the
      technique as a way to measure the speed of visual attention.

PMID- 17209744
TI  - Constant contour integration in peripheral vision for stimuli with good Gestalt
      properties.
AB  - The visual system integrates discrete but aligned local stimuli to form percept
      of global contours. Previous experiments using "snake" contours showed that
      contour integration was mainly present in foveal vision but absent or greatly
      weakened in peripheral vision. In this study, we demonstrated that, for contour
      stimuli such as circles and ellipses, which bore good Gestalt properties, contour
      integration for shape detection and discrimination was nearly constant from the
      fovea to up to 35 degrees visual periphery! Contour integration was impaired by
      local orientation and position jitters of contour elements, indicating that the
      same local contour linking mechanisms revealed with snake contour stimuli also
      played critical roles in integration of our good Gestalt stimuli. Contour
      integration was also unaffected by global position jittering up to 20% of the
      contour size and by dramatic shape jittering, which excluded non-contour
      integration processes such as detection of various local cues and template
      matching as alternative mechanisms for uncompromised peripheral perception of
      good Gestalt stimuli. Peripheral contour integration also presented an
      interesting upper-lower visual field symmetry after asymmetries of contrast
      sensitivity and shape discrimination were discounted. The constant peripheral
      performance might benefit from easy detection of good Gestalt stimuli, which
      popped out from background noise, from a boost of local contour linking by top
      down influences and/or from multielement contour linking by long-range
      interactions.

PMID- 17209745
TI  - Time dilation in dynamic visual display.
AB  - How does the brain estimate time? This old question has led to many biological
      and psychological models of time perception (R. A. Block, 1989; P. Fraisse, 1963;
      J. Gibbon, 1977; D. L. I. Zakay, 1989). Because time cannot be directly measured
      at a given moment, it has been proposed that the brain estimates time based on
      the number of changes in an event (S. W. Brown, 1995; P. Fraisse, 1963; W. D.
      Poynter, 1989). Consistent with this idea, dynamic visual stimuli are known to
      lengthen perceived time (J. F. Brown, 1931; S. Goldstone & W. T. Lhamon, 1974; W.
      T. Lhamon & S. Goldstone, 1974, C. O. Z. Roelofs & W. P. C. Zeeman, 1951).
      However, the kind of information that constitutes the basis for time perception
      remains unresolved. Here, we show that the temporal frequency of a stimulus
      serves as the "clock" for perceived duration. Other aspects of changes, such as
      speed or coherence, were found to be inconsequential. Time dilation saturated at
      a temporal frequency of 4-8 Hz. These results suggest that the clock governing
      perceived time has its basis at early processing stages. The possible links
      between models of time perception and neurophysiological functions of early
      visual areas are discussed.

PMID- 17209746
TI  - Control of attention and gaze in complex environments.
AB  - In natural behavior, fixation patterns are tightly linked to the ongoing task.
      However, a critical problem for task-driven systems is dealing with unexpected
      stimuli. We studied the effect of unexpected potential collisions with
      pedestrians on the distribution of gaze of subjects walking in a virtual
      environment. Pedestrians on a collision course with the subject were surprisingly
      ineffective in evoking fixations, especially when subjects were additionally
      occupied with another task, suggesting that potential collisions do not
      automatically attract attention. However, prior fixations on pedestrians did
      increase collision detection performance. Additionally, the detection of
      potential collisions led to a short-term change in the strategy of looking at
      subsequent pedestrians. The overall pattern of results is consistent with the
      hypothesis that subjects typically rely on mechanisms that are initiated top-down
      to detect unexpected events such as potential collisions. For this to be
      effective, subjects must learn an appropriate schedule for initiating search
      through experience with the probabilities of environmental events.

PMID- 17209747
TI  - New binary direction aftereffect does not add up.
AB  - Neural adaptation and inhibition are pervasive characteristics of the primate
      brain and are probably understood better within the context of visual processing
      than with any other sensory modality. These processes are thought to underlie
      illusions in which one motion affects the perceived direction of another, such as
      the direction aftereffect (DAE) and direction repulsion. The DAE describes how,
      following prolonged viewing of motion in one direction, the direction of a
      subsequently viewed test pattern is misperceived. In the case of direction
      repulsion, the direction difference between two transparently moving surfaces is
      overestimated. Explanations of the DAE appeal to neural adaptation, whereas
      direction repulsion is accounted for through lateral inhibition. Here, we report
      on a new illusion, the binary DAE (bDAE), in which superimposed slow and fast
      dots moving in the same direction are perceived to move in different directions
      following adaptation to a mixed-speed stimulus. This new phenomenon is
      essentially a combination of the DAE and direction repulsion. Interestingly, the
      magnitude of the bDAE is greater than would be expected simply through a linear
      combination of the DAE and direction repulsion, suggesting that the mechanisms
      underlying these two phenomena interact in a nonlinear fashion.

PMID- 17209748
TI  - Interference from filled delays on visual change detection.
AB  - Failure to detect changes to salient visual input across a brief interval has
      popularized the use of change detection, a paradigm that plays important roles in
      recent studies of visual perception, short-term memory, and consciousness. Much
      research has focused on the nature of visual representation for the pre- and
      postchange displays, yet little is known about how visual change detection is
      interfered with by events inserted between the pre- and postchange displays. To
      address this question, we tested change detection of colors, spatial locations,
      and natural scenes, when the interval between changes was (1) blank, (2) filled
      with a visual scene, or (3) filled with an auditory word. Participants were asked
      to either ignore the filled visual or auditory event or attend to it by
      categorizing it as animate or inanimate. Results showed that the ability to
      detect visual changes was dramatically impaired by attending to a secondary task
      during the delay. This interference was significant for auditory as well as for
      visual interfering events and was invariant to the complexity of the prechange
      displays. Passive listening produced no interference, whereas passive viewing
      produced small but significant interference. We conclude that visual change
      detection relies significantly on central, amodal attention.

PMID- 17209749
TI  - Stereo and motion parallax cues in human 3D vision: can they vanish without a
      trace?
AB  - In an immersive virtual reality environment, subjects fail to notice when a scene
      expands or contracts around them, despite correct and consistent information from
      binocular stereopsis and motion parallax, resulting in gross failures of size
      constancy (A. Glennerster, L. Tcheang, S. J. Gilson, A. W. Fitzgibbon, & A. J.
      Parker, 2006). We determined whether the integration of stereopsis/motion
      parallax cues with texture-based cues could be modified through feedback.
      Subjects compared the size of two objects, each visible when the room was of a
      different size. As the subject walked, the room expanded or contracted, although
      subjects failed to notice any change. Subjects were given feedback about the
      accuracy of their size judgments, where the "correct" size setting was defined
      either by texture-based cues or (in a separate experiment) by stereo/motion
      parallax cues. Because of feedback, observers were able to adjust responses such
      that fewer errors were made. For texture-based feedback, the pattern of responses
      was consistent with observers weighting texture cues more heavily. However, for
      stereo/motion parallax feedback, performance in many conditions became worse such
      that, paradoxically, biases moved away from the point reinforced by the feedback.
      This can be explained by assuming that subjects remap the relationship between
      stereo/motion parallax cues and perceived size or that they develop strategies to
      change their criterion for a size match on different trials. In either case,
      subjects appear not to have direct access to stereo/motion parallax cues.

PMID- 17209750
TI  - Bioacoustic monitoring of aggression in group-housed rhesus macaques.
AB  - Many captive primate facilities house rhesus macaques in multimale-multifemale
      social groups in large enclosures that simulate the natural social and
      environmental features characteristic of the species, enhancing their
      reproductive performance as well as their psychological well-being, yet one of
      the most difficult management problems in socially housed macaques is their
      propensity for exhibiting spontaneous bouts of deleterious aggression. To address
      this management problem, an automated bioacoustic monitoring system might be
      developed that is capable of detecting and forecasting problematic patterns of
      contact aggression. To evaluate the utility of this approach, this study examined
      the magnitude of aggression and the co-occurrence of certain vocalization types
      and aggression in 10 groups of rhesus macaques. The data confirmed aggression as
      a significant problem in rhesus groups and indicated that certain patterns of
      vocalizations are indicative of the type or level of aggression. The detection
      and classification of these vocalization types need further research to
      eventually design and implement an efficacious bioacoustic system for monitoring
      aggression in rhesus macaques.

PMID- 17209751
TI  - The effect of the captive environment on activity of captive cotton-top tamarins
      (Saguinus oedipus).
AB  - This study examined captive cotton-top tamarin (Saguinus oedipus) behavior across
      3 different exhibits: (a) a rainforest (30.5 m in diameter), where tamarins free
      ranged with other species; (b) a caged outdoor exhibit (5 m in diameter); and (c)
      a caged enclosure, with access indoors (6 x 9m) and outdoors (2.5 x 2.5 m). The
      study observed tamarins using focal animal scan sampling in 10 min blocks.
      Scoring was on the percentage of intervals in which they engaged in 12 behaviors.
      The findings show significant differences in activity, inactivity, and visibility
      across exhibits and have important implications for reintroduction efforts.

PMID- 17209752
TI  - The physiological and behavioral impact of sensory contact among unfamiliar adult
      mice in the laboratory.
AB  - Housing mice in the laboratory in groups enables social interaction and is the
      way a laboratory should house mice. However, adult males show reciprocal
      aggression and are therefore frequently housed individually. Alternatively, a
      grid divider, which allows sensory contact by sight and smell but prevents
      fighting and injuries, can separate mice within 1 cage. This study examined the
      influence of this housing method on various physiological and behavioral
      parameters. Adult male mice housed for 10 days with sensory contact to an
      unfamiliar male displayed significant increases in heart rate (HR), body core
      temperature (BT), and motor activity (ACT). Furthermore, the mice suffered
      impaired nest-building behavior and significantly reduced body weight.
      Conversely, males housed in a similar manner with a female companion showed only
      a transient elevation of ACT, BT, and HR. Although no clear beneficial effect of
      housing males with sensory contact to females was evident, this study could not
      exclude it. On the other hand, housing of mature males in this way leads to
      sustained detrimental alterations of physiology and behavior, thus implying
      severe impairment of animal well-being.

PMID- 17209753
TI  - Chinese university students' attitudes toward the ethical treatment and welfare
      of animals.
AB  - An important step in ensuring ethical animal treatment and welfare is to
      understand people's attitudes toward them. However, research is lacking from some
      Asian countries, such as China. This needs improvement. In this study I asked
      Chinese university students about their attitudes toward animal welfare issues.
      The students reported strong concern for the treatment of animals across a broad
      spectrum of issues, although the level of concern varied according to the issue.
      The results are in agreement with recent research showing that Chinese society
      displays generally positive attitudes and behaviors toward animal welfare
      initiatives. This study, combined with previous work reported in the literature,
      suggests that the Chinese public is perhaps philosophically ready to accept and
      support the urgent changes needed to improve animal welfare standards in their
      country.

PMID- 17209754
TI  - Introducing a semi-naturalistic exhibit as structural enrichment for two brown
      bears (Ursus arctos). Does this ensure their captive well-being?
AB  - In this study we used the daily activity pattern and use of space as indicators
      of change in the program of structural enrichment, implemented with 2 subjects of
      the species Ursus arctos in the Barcelona Zoo. We collected 930 sampling points
      in each study phase for each of the individuals: The samples were taken in a
      balanced way at different times of day. We observed a wider range of behavior in
      the male than the female. With respect to the indicators, we observed
      statistically significant differences in behavior in both individuals in the 2
      study phases. Both individuals showed an increase in vigilance, maintenance, and
      inactivity when their enclosure was changed. In terms of the subjects' well
      being, we considered the percentage of stereotyped behavior within acceptable
      limits. The percentage of activity observed in the male was very similar to that
      of individuals of this species in the wild. In terms of the use of space, we
      observed homogeneity only in the male during the enrichment program. The 2
      individuals responded in different ways to the structural enrichment.

PMID- 17209756
TI  - Noise exposure, music, and animals in the laboratory: a commentary based on
      Laboratory Animal Refinement and Enrichment Forum (LAREF) discussions.
AB  - The effects of noise, in general, and music, in particular, on the behavior and
      welfare of animals in the laboratory deserve a great deal of empirical study.
      However, many laboratories must develop their current practices on the basis of
      sparse and conflicting data. With this commentary we seek to establish some of
      the factors that should be taken into account in deciding how to deal with
      sources of uncontrolled or deliberate sound and, specifically, in determining
      whether to play music in the laboratory. Views differ, however, the balance of
      evidence supports the use of quiet music during nonhuman animals' active periods,
      if this practice is introduced with an awareness of the risks to welfare and
      research.

PMID- 17209755
TI  - Animal protection measures in Taiwan: Taiwanese attitudes toward the animal
      protection law and animal shelters.
AB  - This study used a questionnaire, self-administered by 387 Taiwanese citizens, to
      assess Taiwanese perception and knowledge of the Animal Protection Law and
      perception and use of animal shelters. Most respondents (87%) knew that Taiwan
      has legal protection for animals. A -5 to 5 summary score measured knowledge of
      companion animal dog-related legal requirements. The median score was 3,
      indicating that almost all respondents had inadequate knowledge about these
      requirements. Although more dog caregivers had adequate knowledge of the law than
      did nondog caregivers (prevalence ratio = 1.9, 95% confidence interval: 1.1,
      3.2), only 19% had adequate knowledge. Although most respondents (81%) knew
      Taiwan has animal shelters, only 19 (5%) reported visiting or participating in
      shelter activities. Only 6 (32%) of shelter visitors or users had a "good or
      better" impression of services received. Despite low usage of animal shelters,
      most respondents thought shelters should accept (87%) and relocate (90%) unwanted
      animals, capture strays (64%), assist in finding lost pets (79%), and educate the
      public about responsible ownership (85%). More than half (52%) thought shelters
      should perform euthanasia.

PMID- 17209757
TI  - Distressed animal behaviors and some recommendations for improvements at the
      Kuala Lumpur Zoo, Malaysia.
AB  - The artificial living conditions of captive animals present numerous challenges
      for animal caretakers. In this study I explored abnormal behaviors in certain
      caged animals at the Kuala Lumpur Zoo. Findings obtained from observations of
      animals and interviews of the zoo staff are followed by recommendations:
      including the development of standards and manuals, licensing of zoos and
      animals, and increased budgets from governments or alternative sources. Such
      interventions should bring considerable improvements in animal welfare at the
      zoos in the region.

PMID- 17209758
TI  - Overcoming the barriers to the retirement of Old and New World monkeys from
      research facilities.
AB  - In this commentary I aim to raise awareness among researchers and sanctuary
      directors to potential barriers to retiring Old and New World monkeys from
      research facilities. I define a barrier as an opinion or stereotype that prevents
      primate retirement from occurring on a regular basis. By discussing retirement
      barriers and recommending how to overcome them, I aim to increase the frequency
      of retiring monkeys from the laboratory into naturalistic sanctuaries. In this
      article I compile a final list of 10 barriers to retirement-and recommendations
      on how to overcome them-based on responses to forums, comments from primate
      sanctuary directors, information contained in scientific and sanctuary
      literature, and personal experiences. I conclude that researchers will increase
      the frequency of primate retirement by performing the following 5 actions: (a)
      increase communication by networking with sanctuaries, (b) prevent negative
      publicity by developing a confidentiality clause with the sanctuary, (c) increase
      understanding by reviewing the articles written on retiring monkeys into
      sanctuaries, (d) increase funding for primate retirement by including funding
      requests in grant proposals, or (e) by raising private funds.

PMID- 17209760
TI  - Development of self-assembled, tissue-engineered ligament from bone marrow
      stromal cells.
AB  - The human anterior cruciate ligament is ruptured 200,000 times per year in the
      United States, resulting in medical costs of $1 billion. The standard treatment
      is patellar tendon autograft, but this treatment is suboptimal because of lengthy
      recovery time, arthritis, donor site morbidity, and degenerative joint disease.
      This study aimed to engineer scaffold-free ligament analogs from a clinically
      relevant cell source and to examine mechanical and histological properties of the
      resulting engineered tissue. Porcine bone marrow stromal cells were seeded on
      laminin-coated substrates with silk suture segments as anchor points. Cells
      developed into monolayers that subsequently delaminated and self-organized into
      cohesive rod-like tissues that were held in tension above the substrate. After 14
      days of maturation, scanning electron microscopy revealed a well-organized
      extracellular matrix, aligned collagen fibers, and a collagen fibril diameter of
      51.1+/-77 nm. Histological evaluation showed that constructs were composed of
      approximately 60% collagen. During tensile tests to failure, constructs had a
      stress of 2.11 +/- 0.13 MPa, a strain of 28.8 +/- 0.95%, a force of 0.26 +/- 0.02
      N, and a tangent modulus of 15.4+/-1.04 MPa. Mechanically and histologically,
      engineered ligament resembled native embryonic connective tissue and had an
      ultimate stress approximately 15% of native adult mouse tissue.

PMID- 17209761
TI  - Eighteen years of research on AIDS: contribution of and collaborations between
      different world regions.
AB  - The scientific community invests significant resources on HIV/AIDS research to
      confront the current epidemic. We reviewed the medical literature in order to
      evaluate the contribution of different world regions on HIV/AIDS research during
      the past 18 years. We retrieved articles, using an elaborate methodology, from
      three journals focusing on HIV/AIDS between 1986 and 2003, indexed in the Journal
      Citation Reports (JCR) and the Web of Science databases of the Institute for
      Scientific Information (ISI). Comparisons were made by dividing the world into
      nine geographic regions, and by using the human development index (HDI)
      categorization. A total of 9502 articles on HIV/AIDS were retrieved from three
      AIDS journals over an 18-year study period. The United States and Western Europe
      together and five developed out of nine world regions made up a striking 83% and
      92% of the world's research production on HIV/AIDS, respectively. Scientists from
      the developing world participated in 10.4% of the articles published during 1986
      1991, 14.7% during 1992-1997, and 21.3% during 1998-2003. Researchers from
      countries included in the high, medium, and low HDI category produced 2240, 9,
      and 15 articles per billion population, respectively. About half of articles
      originating in Latin America and the Caribbean and half in Asia were produced in
      collaboration with the United States. However, 40% of articles from Africa and
      58% from Eastern Europe were produced in cooperation with Western Europe.
      Collaboration between researchers within developing regions was negligible. The
      vast majority of the world's research on AIDS is produced in the developed world.
      Although research production was minimal in the developing world, we found that
      regions included in the low and medium HDI categories showed a higher proportion
      of increase in research productivity than the developed countries. International
      collaborations should significantly increase and expand beyond the traditional
      cultural and political lines of international relationships.

PMID- 17209762
TI  - Genomic diversity in the regulatory nef gene sequences in Indian isolates of HIV
      type 1: emergence of a distinct subclade and predicted implications.
AB  - The regulatory functional nef gene is known to mediate a cascade of events during
      pathogenesis in HIV infection. Variability in the nef gene sequences of HIV-1 A
      and B subtypes has been well documented. Reasonable data are also available on
      the pattern of genomic changes in the nef gene of African strains of HIV-1
      subtype C, but very little is known about heterogeneity in the nef gene of Indian
      strains of HIV-1 subtype C, which accounts for 90% of the estimated 5.2 million
      cases of HIV infection in India. This is a huge number and, therefore, it is
      important to reveal the extent of sequence variability in the nef gene of HIV-1
      subtypes circulating in different parts of India. We carried out full-length nef
      gene (approximately 620 bp) sequencing on a large number of clinical isolates of
      HIV-1 circulating in different geographic regions of India. Comparative and
      phylogenetic analysis revealed 88% (38/43) of cases was HIV-1 subtype C; four
      cases were diagnosed as subtype A and only one as subtype B. Although most of the
      crucial functional motifs of the nef gene were conserved, we did observe a few
      important variations in juxtapositions to functional domains. Interestingly,
      analyzed nef sequences showed an evolving pattern of segregation away from those
      reported from other parts of the world, to form a distinct Indian subclade.
      Deduced amino acid (aa) sequences used to predict HLA binding epitopes for
      consensus nef gene sequences of Indian strains of HIV-1 revealed two HLA subtype
      binding domains, GAFDLSFFL (at aa 83) and LTFGWCFKL (at aa 136), in high
      frequency. The findings from the present study may encourage use of nef gene in
      molecular diagnostics/genotyping, keeping track of the evolutionary trend and
      pinpointing the emergence of recombinant strains, and in the future, designing a
      multiepitope HIV vaccine suitable for the Indian population.

PMID- 17209763
TI  - Short partially double-stranded oligodeoxynucleotide induces reverse
      transcriptase/RNase H-mediated cleavage of HIV RNA and contributes to abrogation
      of infectivity of virions.
AB  - We describe a novel mechanism of viral RNA eradication by an oligodeoxynucleotide
      A (ODN A) directly in HIV virions. The ODN A consists of an antisense and a
      passenger strand, and was designed to target the polyp-urine tract (PPT) of HIV
      1, a conserved region of the viral genome. It leads to HIV reverse
      transcriptase/ribonuclease H (RT/RNase H)-dependent degradation of the RNA in
      viral particles. Illimaquinone, a specific inhibitor of RNase H, activity of HIV
      RT/RNase H, prevents RNA cleavage. The effect of the ODN A is sequence-specific
      and the passenger strand is important, since a lack or alteration of this strand
      reduces the antiviral activity of the ODN. ODN A has a stronger antiviral effect
      compared to a control ODN CO, targeted to a site outside of the PPT. The
      pretreatment with ODN A strongly reduced the infectivity of virions in cell
      culture in the absence of any DNA carriers or detergents.

PMID- 17209764
TI  - Rate of virologic failure and selection of drug resistance mutations using
      different triple nucleos(t)ide analogue combinations in HIV-infected patients.
AB  - Virologic failure seems to occur more frequently in HIV-infected patients treated
      with triple nucleoside analogue (NA) combinations than with regimens including
      nonnucleoside reverse transcriptase inhibitors or protease inhibitors. However,
      the rate of failure and resistance profiles may differ with distinct triple NA
      combinations. A retrospective review of all HIV-infected individuals who received
      triple NA combinations at our institution was conducted. Virologic failure was
      defined as lack of achievement of plasma HIV-RNA<50 copies/ml at week 16
      following initiation of antiretroviral therapy or as viral rebound in subjects
      with prior undetectable viremia. Genotypic analyses were performed at the time of
      first virological failure. Of the 261 patients identified, 13 were drug naive,
      126 had underwent simplification, and 122 were antiretroviral-experienced
      patients with detectable viral load. Virologic failure was recorded in 95 (36.4%)
      after an average follow-up of 19 months. Rates were 0.67 in drug-naive, 0.55 in
      simplification, and 2.38 in rescue interventions for 100 persons-month follow-up.
      Factors associated with virologic failure in the multivariate Cox regression
      analysis were rescue vs naive or simplification strategies (OR 2.6; 95% CI 1.6
      4.2) and using tenofovir as part of the combination (OR 2.04; 95% CI 1.3-3.2). In
      contrast, the use of AZT prevented virologic failure (OR 0.52; 95% CI 0.3-0.8).
      M184V was the most frequent resistance mutation (75.4%), followed by T215Y
      (52.5%) and K65R (14.8%). Of note, K65R did not develop in patients taking AZT
      nor in those with prior thymidine-associated mutations (TAMs). Conversely,
      subjects who developed K65R did not accumulate TAMs. Virologic failure is
      relatively frequent in patients treated only with triple NA regimens,
      particularly in the setting of rescue therapy. The use of TDF might be associated
      with a higher risk of virologic failure and, conversely, AZT might be protective.
      The presence of TAMs precluded the selection of K65R in patients treated with
      TDF. Resistance pathways for TDF and thymidine analogues seem to be divergent and
      could be the basis to explore a synergism between these drugs.

PMID- 17209765
TI  - Incidence of and factors associated with hepatocellular carcinoma among hepatitis
      C virus and human immunodeficiency virus coinfected patients with decompensated
      cirrhosis.
AB  - We compared the incidence of and factors associated with hepatocellular carcinoma
      (HCC) among hepatitis C virus (HCV)-monoinfected subjects and human
      immunodeficiency virus (HIV)/HCV-coinfected individuals, both with decompensated
      cirrhosis. In a retrospective study, a cohort of 180 individuals with HIV
      coinfection and 1037 HCV-monoinfected patients with decompensated HCV-related
      cirrhosis from eight centres in Spain were analyzed. HCC was found in 234 (23%)
      HCV-monoinfected subjects and in four (2%) HIV-coinfected subjects (p<0.001). At
      the time of the first hepatic decompensation, 188 (17%) and 4 (2%) (p<0.001)
      patients in the former and in the latter group, respectively, showed HCC. Fifty
      four (11%) patients without HCC at baseline developed such a disease during
      follow-up. There were no incident cases among the HIV-coinfected population. The
      density of incidence (95% IC) of HCC in HIV/HCV-coinfected and HCV-monoinfected
      patients was 0 (0-1.70) and 3.31 (2.70-4.64) cases per 100 person-years
      (p<0.001), respectively. Lack of HIV infection [adjusted odds risk (AOR) (95%
      IC)=16.7 (3.9-71.1)] and high alanine aminotransferase levels [AOR (95% IC)=2.5
      (1.1-5)] were the only two independent predictors of the emergence of HCC. In the
      group of patients in whom the date of HCV infection could be estimated, the time
      elapsed until HCC diagnosis was shorter among HIV-coinfected subjects. The
      incidence of HCC in patients with HCV-related cirrhosis after the first hepatic
      decompensation is lower in HIV-coinfected patients. This is probably due to the
      fact that HIV infection shortens the survival of HCV-coinfected patients with end
      stage liver disease to such an extent that HCC not had a chance to emerge.

PMID- 17209766
TI  - Inappropriately low glycated hemoglobin values and hemolysis in HIV-infected
      patients.
AB  - In order to test the accuracy of glycated hemoglobin (HbA1c) in predicting mean
      glycemia in HIV-infected patients, we recorded consecutive HbA1c measurements
      from 1238 non-HIV-infected and 112 HIV-infected patients, all devoid of any
      hemoglobinopathy, in a retrospective, transversal study. Mean fasting glycemia
      from the six previous weeks (measured-Gly) and HbA1c-estimated glycemia [HbA1c
      Gly (1.85x%HbA1c-4.78) mM] were compared. Mean hemoglobin, red cell volume, serum
      creatinine, CD4 count, and HIV viral load from the same period were collected in
      HIV-infected patients. Although measured-Gly was not significantly different
      between non-HIV-infected (6.95+/-3.23 mM) and HIV-infected patients (6.62+/-2.42
      mM), HbA1c underestimated the mean fasting glycemia by 12.3% in HIV-infected as
      compared to non-HIV-infected patients (p=0.0001). The difference "measured-Gly
      HbA1c-Gly" was correlated with the red cell volume (p<0.0001) in HIV-infected
      patients. We then searched for the presence of subclinical hemolysis, a cause of
      both macrocytosis and reduced HbA1c levels, in HIV-infected patients. To this
      end, we prospectively measured serum haptoglobin in 249 consecutive samples from
      HIV-infected subjects without any known cause of hemolysis. A very low
      haptoglobin level, a marker of hemolysis, was frequent and negatively correlated
      with the red cell volume in these patients. Treatment with nucleoside analogues
      was significantly associated with macrocytosis and low haptoglobin. In
      conclusion, HbA1c could be inappropriately low in HIV-infected patients. Its
      underestimation of mean fasting glycemia could be due to an antiretroviral
      induced subclinical hemolysis, but further studies are needed to explore this
      hypothesis. Self-monitoring of blood glucose and search for latent hemolysis
      should be promoted in diabetic HIV-infected patients.

PMID- 17209767
TI  - Cross-sectional study to evaluate factors associated with adherence to
      antiretroviral therapy by Brazilian HIV-infected patients.
AB  - Antiretroviral therapy success is highly dependent on the ability of the patient
      to fully adhere to the prescribed treatment regimen. We present the results of a
      cross-sectional study that evaluates the predictive value of a self-administered
      questionnaire of adherence to antiretroviral (ARV) therapy. Study participants
      were interviewed using a 36-item Patient Medication Adherence Questionnaire
      (PMAQ) designed to assess knowledge about ARV therapy, motivation to adhere to
      treatment, and behavioral skills. Plasma HIV-1 RNA levels were correlated with
      the results obtained from the PMAQ. Of the 182 study participants, 82 (45%) were
      receiving their initial ARV regimen. Of the remaining patients, 39 (21%) and 61
      (34%) were on a second or additional ARV regimen, respectively. An undetectable
      viral load was documented in 47/62 (76%) patients on their first regimen who
      reported missing medication on less than 4 days in the last 3 months. The PMAQ
      had a higher predictive value of plasma viral suppression for patients in the
      initial regimen than for patients in salvage therapy. The overall predictive
      value of the PMAQ to identify adherence was 74%, and 59% for nonadherence, with
      an overall efficacy of 64%. Of the 74 patients (45%) who did not understand the
      concept of antiretroviral therapy, 80% were failing or had previously failed the
      ARV treatment. Of 35 patients with doubts about their HIV status or skeptical of
      the benefits of ARV therapy, 29 (84%) were nonadherent. Despite the positive
      predictive value of PMAQ in identifying adherence, self-reported adherence is not
      a sufficiently precise predictor of treatment success to substitute for viral
      load monitoring. On the other hand, the use of such an instrument to identify
      factors associated with nonadherence provides an excellent opportunity to apply
      early intervention designed to specifically address factors that might be
      contributing to the lack of adherence prior to regimen failure.

PMID- 17209768
TI  - Quantitative analysis of human endogenous retrovirus-W env in neuroinflammatory
      diseases.
AB  - Although human endogenous retroviruses (HERVs) constitute 8% of the human genome,
      their role(s) in health and disease remain uncertain. Nonetheless, increased HERV
      gene activity has been reported in neuroinflammatory diseases such as multiple
      sclerosis (MS). The human endogenous retrovirus (HERV)-W7q envelope gene encodes
      a glycosylated envelope protein, syncytin-1, which is expressed in many tissues.
      Analysis of HERV envelopes (env) revealed a selectively increased abundance of
      syncytin-1 encoding RNA in brains from patients with MS (p<0.01) relative to non
      MS patients. However, HERV env expression from blood-derived leukocytes did not
      differ between groups. A quantitative PCR-based assay for syncytin-1 RNA showed
      that median viral RNA levels were higher in brains of MS patients (5.0 log10
      copies/microg RNA) relative to non-MS patients (4.6 log10 copies/microg RNA)
      (p<0.05). Median syncytin-1 DNA levels in MS brains (9.8 log10/microg DNA) were
      higher than non-MS brain tissue (7.9 log10/microg DNA) (p<0.001) without evidence
      of new integration events. In contrast, there were no differences in syncytin-1
      RNA copy numbers between groups in both CSF (non-MS: 5.0 log10/ml versus MS: 3.8
      log10/ml) and plasma (non-MS: 5.033 log10/ml versus MS: 2.9 log10/ml). These
      observations emphasize the selective induction of syncytin-1 in brain tissue of
      MS patients but also illustrate the complex dynamics of this retroelement in
      neuroinflammatory processes.

PMID- 17209769
TI  - Continued evolution in gp41 after interruption of enfuvirtide in subjects with
      advanced HIV type 1 disease.
AB  - Careful examination of viral dynamics during antiretroviral treatment can provide
      important insights into HIV pathogenesis. We examined viral evolution during and
      after enfuvirtide (T-20) treatment with an objective of defining the
      characteristics of viral evolution during advanced HIV immunodeficiency.
      Specifically, we examined the viral quasispecies from nine patients who
      experienced incomplete viral suppression on an enfuvirtide-based regimen, and who
      subsequently interrupted enfuvirtide while remaining on a stable optimized
      background regimen (enfuvirtide "partial treatment interruption"). On average,
      eight clones were sequenced from three time points: pre-enfuvirtide, post
      enfuvirtide failure, and post-enfuvirtide interruption. We utilized a Bayesian
      hierarchical phylogenetic model to assess the evolutionary relatedness of the
      virus that emerged over time. In most subjects, interruption of enfuvirtide was
      associated with continued viral evolution as enfuvirtide mutations waned; in no
      subject did we find clear evidence supporting the reemergence of archived wild
      type variants (Bayes factor=30.2, p=0.01). Evidence supporting ongoing viral
      evolution was particularly strong in subjects whose virus remained diverse or
      became more diverse during enfuvirtide therapy. In contrast to observations when
      all drugs are interrupted, loss of resistance during enfuvirtide interruption is
      most likely due to ongoing viral evolution (and back-mutation), rather than
      emergence of an archived virus.

PMID- 17209770
TI  - Serological and molecular typing of HIV type 1 infection in the Tiriyo tribe, a
      native Indian community of the Amazon region of Brazil.
AB  - The seroprevalence and the occurrence of an HIV-1 subtype was assessed in blood
      samples of the Tiriyo tribe. Antibody was found in 0.6% and the molecular
      analysis of the pro region detected the emergence of a subtype B for the first
      time in a native Indian tribe of the Amazon region of Brazil.

PMID- 17209771
TI  - Identification of a novel HIV type 1 CRF01_AE cytotoxic T lymphocyte (CTL)
      epitope restricted by an HLA-Cw0602 allele and a novel HLA-A0206/peptide
      restriction.
AB  - This report describes specific T cell responses to HIV-1 CRF01_AE Env and A Gag
      peptides in 20 HIV-1 CRF01_AE-infected Thai individuals using an interferon-gamma
      (IFN-gamma) enzyme-linked immunospot (ELISpot) assay. Twenty-six potentially
      novel HLA class I-restricted CD8+ T cell epitopes were identified in 14/20
      subjects. Fine mapping analysis using the chromium release cytotoxic T lymphocyte
      (CTL) assay revealed a novel HLA-Cw0602 restricted epitope of HIV-1 CRF01_AE Env
      (NAKTIIVHL) and a previously identified HIV-1 A Gag epitope (ATLEEMMTA) with a
      novel HLA-A0206 restriction.

PMID- 17209772
TI  - Evidence for CTL-mediated selection of Tat and Rev mutants after the onset of the
      asymptomatic period during HIV type 1 infection.
AB  - The evolution of HIV-1 sequences over time is the result of the selection of
      mutant variants that have escaped from host immune responses or the outgrowth of
      mutants with increased viral replication, or both. We investigated the
      contribution of both selection processes to the overall evolution of the Tat and
      Rev regulatory gene sequences from four individuals, ranging in time from just
      prior to seroconversion to stable asymptomatic infection. After sequencing at
      least 15 clones per sample per gene, we analyzed the sequence evolution of the
      MHC-I motifs that were predicted from the MHC-I haplotypes of these patients. For
      each identified Tat sequence, we tested the activity of the corresponding encoded
      protein in a transactivation assay in vitro. Our results suggest that the
      evolution of the Tat and Rev sequences from these individuals can be explained by
      mutational escape of the MHC-I epitopes and that no mutations that replaced the
      original sequences in the viral population are associated with either an increase
      or decrease in Tat activity. CTL-mediated selection appears to be an important
      determinant of HIV-1 regulatory gene sequence evolution during the early stages
      of infection.

PMID- 17209773
TI  - Phylogenetic analysis of env, gag, and tat genes of HIV type 1 detected among the
      injecting drug users in West Bengal, India.
AB  - A recent occurrence of HIV-1 seropositivity among a group of injecting drug users
      (IDUs) in Darjeeling, a hilly district in northern West Bengal, revealed overall
      11.8% HIV seroprevalence. Our study based on env (C2-V3), gag (p24-p7), and tat
      (exon-1) genomic regions of HIV-1 detected among this population showed that
      Darjeeling IDU sequences belonged to subtype C. Interestingly, the IDU sequences
      from Darjeeling were again found to be closer to the C strains from Manipur, a
      northeastern state in India, which is linked to the Golden Triangle via the
      Manipur-Myanmar border, rather than the IDU C sequences from Nepal, a neighboring
      country of India. The outgroup reference strains from different sites of IDU
      driven epidemics in the world like Russia, Vietnam, Thailand, and Spain belonged
      to the nonsubtype C group and formed separate clusters from the subtype C cluster
      in our analysis. These results indicate a rapid spread of HIV-1 by possible drug
      trafficking along international boundaries, which might also help in the invasion
      of HIV-1 among IDUs of Darjeeling through the Manipur-Myanmar border of India.

PMID- 17209775
TI  - Resistance mutational analysis of HIV type 1 subtype C among rural South African
      drug-naive patients prior to large-scale availability of antiretrovirals.
AB  - Baseline HIV-1 resistance data are important for resistance monitoring purposes
      especially in regions initiating large-scale antiretroviral treatment programs.
      We examined 40 protease and 35 reverse transcriptase amino acid sequences of HIV
      1 subtype C from drug inexperienced patients from rural settings in South Africa
      for resistance mutations. Samples were collected between 2001 and 2004 prior to
      the availability of antiretrovirals through public health institutions. Ninety
      five percent of patients had no major mutations in the protease gene, although
      substitutions M46L (2.5%) and G73S (2.5%), which according to the Stanford
      Genotypic Resistance Interpretation Algorithm are considered major mutations,
      were detected. In addition, a high prevalence of minor mutations was observed in
      the protease, with at least three minor resistance-associated mutations in 37% of
      the isolates. An isoleucine insertion at codon 37 was detected in one sequence.
      Most of the RT sequences were wild-type, although V118I (8.5%) and Y318F (5.7%)
      associated with resistance to lamivudine and nevirapine, respectively, were
      observed. Our data suggest that major resistance mutations among the drug
      inexperienced population in South Africa may be rare, and routine resistance
      testing before the initiation of therapy in this initial stage of the treatment
      program may not be necessary.

PMID- 17209774
TI  - N88D facilitates the co-occurrence of D30N and L90M and the development of
      multidrug resistance in HIV type 1 protease following nelfinavir treatment
      failure.
AB  - Nelfinavir was once one of the most commonly used protease inhibitors (PIs). To
      investigate the genetic mechanisms of multidrug resistance in protease isolates
      with the primary nelfinavir resistance mutation D30N, we analyzed patterns of
      protease mutations in 582 viruses with D30N from 460 persons undergoing HIV-1
      genotypic resistance testing at Stanford University Hospital from 1997 to 2005.
      Three patterns of mutational associations were identified. First, D30N was
      positively associated with N88D but negatively associated with N88S. Second, D30N
      and L90M were negatively associated except in the presence of N88D, which
      facilitated the co-occurrence of D30N and L90M. Third, D30N+N88D+L90M formed a
      stable genetic backbone for the accumulation of additional protease inhibitor
      (PI) resistance mutations. In 16 patients having isolates with more than one
      combination of mutations at positions 30, 88, and 90, all exhibited one of the
      steps in the following progression: D30N-->D30N+N88D-->D30N+N88D+L90M-
      >D30N+N88D+L90M+(L33F+/-I84V or M46I/L+/-I54V). Although nelfinavir is now used
      less frequently than other PIs, the well-delineated mutational pathway we
      describe is likely to influence patterns of cross-resistance in viruses from
      persons who experience virologic failure while receiving this PI.

PMID- 17209776
TI  - The mental foramen and nerve: clinical and anatomical factors related to dental
      implant placement: a literature review.
AB  - BACKGROUND: The mental foramen is a strategically important landmark during
      osteotomy procedures. Its location and the possibility that an anterior loop of
      the mental nerve may be present mesial to the mental foramen needs to be
      considered before implant surgery to avoid mental nerve injury. METHODS: Articles
      that addressed the position, number, and size of the mental foramen, mental nerve
      anatomy, and consequences of nerve damage were evaluated for information
      pertinent to clinicians performing implant dentistry. RESULTS: The mental foramen
      may be oval or round and is usually located apical to the second mandibular
      premolar or between apices of the premolars. However, its location can vary from
      the mandibular canine to the first molar. The foramen may not appear on
      conventional radiographs, and linear measurements need to be adjusted to account
      for radiographic distortion. Computerized tomography (CT) scans are more accurate
      for detecting the mental foramen than conventional radiographs. There are
      discrepancies between studies regarding the prevalence and length of the loop of
      the mental nerve mesial to the mental foramen. Furthermore, investigations that
      compared radiographic and cadaveric dissection data with respect to identifying
      the anterior loop reported that radiographic assessments result in a high
      percentage of false-positive and -negatives findings. Sensory dysfunction due to
      nerve damage in the foraminal area can occur if the inferior alveolar or mental
      nerve is damaged during preparation of an osteotomy. CONCLUSIONS: To avoid nerve
      injury during surgery in the foraminal area, guidelines were developed based on
      the literature with respect to verifying the position of the mental foramen and
      validating the presence of an anterior loop of the mental nerve. These guidelines
      included leaving a 2 mm zone of safety between an implant and the coronal aspect
      of the nerve; observation of the inferior alveolar nerve and mental foramen on
      panoramic and periapical films prior to implant placement; use of CT scans when
      these techniques do not provide clarity with respect to the position of the
      nerve; surgical corroboration of the mental foramen's position when an anterior
      loop of the mental foramen is suspected of being present or if it is unclear how
      much bone is present coronal to the foramen to establish a zone of safety (in
      millimeters) for implant placement; once a safety zone is identified, implants
      can be placed anterior to, posterior to, or above the mental foramen; and prior
      to placing an implant anterior to the mental foramen that is deeper than the
      safety zone, the foramen must be probed to exclude the possibility that an
      anterior loop is present. In general, altered lip sensations are preventable if
      the mental foramen is located and this knowledge is employed when performing
      surgical procedures in the foraminal area.

PMID- 17209777
TI  - Quality of trials in a systematic review of powered toothbrushes: suggestions for
      future clinical trials.
AB  - BACKGROUND: This study aimed to assess the quality of reports of randomized
      controlled trials (RCTs) comparing manual and powered toothbrushes and provide
      advice on how future trials might be improved. METHODS: Studies were identified
      in the Cochrane systematic review of RCTs comparing powered versus manual
      toothbrushes. Reports were assessed against predefined criteria on the design of
      the studies to determine the effectiveness of the brushes in everyday home use
      and on their methodological quality. RESULTS: Only 42 of 297 identified studies
      satisfied the inclusion criteria and were eligible for inclusion in the review.
      Many studies were excluded for more than one reason. Fifteen studies employed
      split-mouth designs that may have changed toothbrushing behavior. Of 42 included
      RCTs, the generation of randomization sequence was adequate in 15 trials and
      concealment of allocation was adequate in 16 trials. Intention-to-treat analysis
      was reported in only five studies. Plaque data were reported using 10 different
      indices and gingivitis with nine indices. Only 12 trials lasted 3 months or
      longer, and there were no data on the benefits of powered toothbrushes for
      periodontal attachment. CONCLUSIONS: Some designs created an artificial research
      environment that may have undermined the findings. Authors of toothbrush trials
      should consider the Consolidated Standards of Reporting Trials statement. Greater
      standardization of the indices used is required. Trials of longer duration would
      enhance the evaluation of powered toothbrushes. Data on thresholds for clinically
      significant differences in plaque and gingivitis levels would help to determine
      whether oral hygiene aids provide important health benefits.

PMID- 17209778
TI  - A case-control study on the association of human leukocyte antigen-A*9 and -B*15
      alleles with generalized aggressive periodontitis in an Indian population.
AB  - BACKGROUND: The genes encoding the human leukocyte antigens (HLAs; major
      histocompatibility complex [MHC]) have been considered candidate markers for
      periodontitis because they are involved in regulating immune responses. Several
      studies have examined this association, and despite the inconclusive results, the
      antigens HLA-A9 and HLA-B15 have been found to be consistently associated with
      the destructive forms of periodontitis in many populations. Ethnic factors are
      considered to be a major variable for evaluating the predisposition to the
      disease. The purpose of the present study was to: 1) assess the association of
      HLA-A*9 and HLA-B*15 with generalized aggressive periodontitis (GAgP) and 2)
      evaluate the role of these genetic risk factors in influencing the severity of
      GAgP in a South Indian population. METHODS: Forty GAgP patients (cases) and 80
      periodontally and systemically healthy subjects (controls) participated in this
      study. HLA-A*9 and HLA-B*15 typing was carried out using the polymerase chain
      reaction with sequence specific primers (PCR-SSP)-based molecular method.
      RESULTS: HLA-B*15 was a significant risk factor for GAgP and was positively
      correlated with the disease severity, whereas HLA-A*9 had no association with the
      disease. The haplotype of HLA-A*9:B*15 did not impart any additional risk for
      GAgP compared to that imparted by HLA-B*15 alone. CONCLUSIONS: To our knowledge,
      this is the first report on HLA-B*15 association with GAgP in an Indian
      population. The finding of HLA-B*15 as a risk factor may have potential use in
      the future management of GAgP. The precise disease-causing mechanism of this HLA
      disease association and whether this association is "causal" or "casual" need to
      be evaluated further.

PMID- 17209779
TI  - Characterization of minocycline transport by human neutrophils.
AB  - BACKGROUND: Tetracyclines are used in periodontal therapy as antimicrobial agents
      and as inhibitors of matrix metalloproteinases. Neutrophils appear to accumulate
      minocycline and other tetracyclines through a mechanism that has not been fully
      characterized. METHODS: The transport of minocycline and other tetracyclines by
      isolated human neutrophils was characterized by measuring the increase in cell
      associated fluorescence. RESULTS: Quiescent neutrophils took up minocycline
      through a saturable, concentrative, sodium-dependent mechanism with a Michaelis
      constant (K(m)) of 153 micro g/ml (501 microM) and a maximal velocity of 240
      ng/minute/10(6) cells. The efficiency of minocycline transport was not influenced
      significantly by a two-unit variation in extracellular pH and was not enhanced
      upon cell activation with phorbol myristate acetate. Neutrophil incubation in
      medium containing 10 micro g/ml minocycline, doxycycline, or tetracycline yielded
      steady-state intracellular/extracellular concentration ratios of approximately
      64.0, 7.5, or 1.8, respectively. The dilution of extracellular minocycline or
      doxycycline triggered efflux from cells loaded with these antibiotics.
      Minocycline transport was competitively inhibited by the organic cations
      carnitine, diphenhydramine, and verapamil, but penicillin and other organic
      anions failed to produce inhibition. CONCLUSION: Transport of tetracyclines by
      neutrophils could potentially enhance the effectiveness of these agents in
      periodontal therapy by enhancing or sustaining their therapeutic levels at
      inflammatory sites and by enhancing the killing of phagocytosed bacterial
      pathogens.

PMID- 17209780
TI  - Enhancing effects of areca nut extracts on the production of interleukin-6 and
      interleukin-8 by peripheral blood mononuclear cells.
AB  - BACKGROUND: The habit of chewing areca quid (AQ) has been implicated in oral
      pathogenesis, including periodontal disease. Little is understood about the roles
      of AQ in the cytokine secretion by immune cells. The study examined the effects
      of areca nut, the major ingredient of AQ, on the production of interleukin (IL)-6
      and IL-8 by peripheral blood mononuclear cells (PBMC), the immunocompetent cells.
      The possible role of oxidative stress of areca nut was also examined. METHODS:
      Extracts of ripe areca nut (rANE) and tender areca nut (tANE) were examined for
      their cytotoxic effects on human PBMC using the trypan blue exclusion test. The
      production of IL-6 and IL-8 by ANE-treated PBMC was analyzed using enzyme-linked
      immunosorbent assay and reverse transcription-polymerase chain reaction. Effects
      of an antioxidant, pyrrolidine dithiocarbamate (PDTC), on ANE-induced cytokine
      secretion were also studied. RESULTS: At the experimental conditions, 20 micro
      g/ml rANE decreased cell viability significantly, whereas no significant effect
      of tANE (< or =80 micro g/ml) was observed. Both rANE (< or =20 micro g/ml) and
      tANE (< or =160 micro g/ml) significantly increased the secretion of IL-6 and IL
      8 by PBMC in a dose- and time-dependent manner. The altered mRNA expression of IL
      6 by rANE and tANE was also observed. Moreover, the stimulating effects of rANE
      on cytokine expression in PBMC could be attenuated by PDTC, suggesting that the
      oxidative stress of rANE may play a role. CONCLUSIONS: Markedly enhancing effects
      of ANE on PBMC-released inflammatory cytokines might cause a sustained cytokine
      rich inflammatory milieu in oral cavity of AQ chewers. These excessive cytokines
      from ANE-treated immune cells may impair periodontal health.

PMID- 17209781
TI  - Analysis of tumor necrosis factor-alpha, transforming growth factor-beta,
      interleukin-10, IL-6, and interferon-gamma gene polymorphisms in patients with
      chronic periodontitis.
AB  - BACKGROUND: Cytokine gene polymorphisms may have an impact on the susceptibility
      to and progression of chronic periodontitis. In this study, we analyzed the -1082
      interleukin-10 (IL-10), -308 tumor necrosis factor-alpha (TNF-alpha),
      transforming growth factor-beta 1 (TGF-beta1) (codons 10 and 25), -174IL-6, and
      +874 interferon-gamma (IFN-gamma) gene single-nucleotide polymorphisms in a
      cohort of patients with chronic periodontal disease. METHODS: The diagnosis was
      made on the basis of standardized clinical and radiographic criteria. A total of
      122 adult patients with chronic periodontitis and 114 unrelated, ethnically and
      age-matched white control subjects were genotyped by a polymerase chain reaction
      sequence-specific primer. RESULTS: The number of individuals carrying the -174IL
      6 CC genotype was significantly higher in the group of patients than in the
      control group (odds ratio [OR] = 1.896; 95% confidence interval [CI] = 1.106 to
      3.250; P = 0.0283). The TGF-beta1 (codon 25) GG (Arg(25)/Arg(25)) genotype was
      detected more frequently in control subjects than in periodontitis patients (OR =
      0.459; 95% CI = 0.230 to 0.920; P = 0.0421). CONCLUSION: The -174IL-6 and TGF
      beta1 (codon 25) single-nucleotide polymorphisms are associated with
      susceptibility to chronic periodontitis in the population studied.

PMID- 17209782
TI  - Histologic and ultrastructural analysis of regenerated bone in maxillary sinus
      augmentation using a porcine bone-derived biomaterial.
AB  - BACKGROUND: The purpose of the present study was the histologic and
      ultrastructural evaluation of a biomaterial composed of cortical pig bone in the
      form of granules. METHODS: After maxillary sinus augmentation using this
      biomaterial, 10 specimens were retrieved after 5 months in 10 patients using this
      biomaterial. The specimens were processed to be observed under light microscopy
      (LM) and transmission electron microscopy (TEM). Histomorphometric measurements
      were presented by means +/- standard deviations. RESULTS: LM showed that most of
      the particles were surrounded by newly formed bone. In some areas, the osteoid
      matrix was present; however, mainly compact bone was present at the interface.
      There was no evidence of an acute inflammatory infiltrate. The newly formed bone
      was 36% +/- 2.8% and marrow spaces were 38% +/- 1.6%, whereas residual grafted
      material was 31% +/- 1.6%. Under TEM, all phases of bone formation (osteoid
      matrix, woven, and lamellar bone) were observed in proximity with the biomaterial
      particles. The bone-biomaterial interface showed a close contact between the
      porcine bone particles and the surrounding bone that had mainly features of
      mature bone with numerous osteocytes. A lamina limitans was sometimes present at
      this interface. CONCLUSIONS: According to our knowledge, this is the first study
      presenting data on TEM of a porcine bone-derived biomaterial used in sinus
      augmentation procedures in humans. Our findings show that this is a biocompatible
      biomaterial that can be used for maxillary sinus augmentation procedures without
      interfering with the normal reparative bone processes.

PMID- 17209783
TI  - Effects of sinus membrane perforations on the success of dental implants placed
      in the augmented sinus.
AB  - BACKGROUND: Maxillary sinus lifting procedure enables clinicians to place implant
      supported prostheses even in cases with very limited vertical bone height of the
      maxillary sinus. The aim of this study was to evaluate the implant success with
      regard to effects of the sinus membrane perforations that occurred during sinus
      lifting surgery. METHODS: The study group consisted of 91 patients (29 females
      and 54 males) with edentulous posterior maxilla. Implant placement combined with
      sinus lifting surgery was performed, and 259 implants were inserted. Sinus
      membrane perforations were detected in 12 sinus sites. After proper treatment of
      perforations, 26 implants were placed into perforated sinus areas. Baseline
      panaromic radiographs were taken before the beginning of prosthetic treatment.
      Panaromic radiographs taken at the last recall were used for evaluation and
      compared to the baseline panaromic radiographs using image analysis software to
      reveal the peri-implant resorption rate for the implants placed in perforated and
      non-perforated sinus area. The modified sulcus bleeding index and plaque index
      were used for the assessment of soft tissue conditions. RESULTS: Eleven implants
      were lost during the follow-up period, resulting in an overall survival rate of
      95.9%. Two failures occurred in the group with sinus perforations. There was no
      statistically significant difference regarding peri-implant bone resorption (P =
      0.778) and soft tissue conditions for implants placed into perforated-augmented
      sinus areas and augmented sinus areas. CONCLUSION: Within the limits of this
      study, perforation of the sinus membrane did not compromise the osseointegration
      process or the success of dental implants placed in the augmented maxillary
      sinus.

PMID- 17209784
TI  - A 2-year clinical report of patients treated with two loading protocols for
      mandibular overdentures: early versus conventional loading.
AB  - BACKGROUND: The original Branemark protocol for dental implant treatment was
      based on submerged healing prior to loading. In recent years, immediate/early
      functional loading has been reported to be possible with high success for various
      indications including two splinted mandibular implants supporting an overdenture.
      However, there are a limited number of studies regarding the early loading
      protocol for two unsplinted mandibular implants supporting an overdenture.
      METHODS: A total of 26 edentulous patients were treated with two unsplinted
      dental implants supporting mandibular overdentures. All implants were placed in
      the canine regions of each mandible according to the one-stage surgery. For the
      test group, overdentures were connected 1 week after surgery, and for the control
      group, overdentures were connected 3 months after surgery. Peri-implant
      parameters were recorded 1, 6, 12, 18, and 24 months after surgery. Marginal bone
      levels were evaluated at implant placement and after 6, 12, 18, and 24 months.
      Clinical stability measurements were performed at surgery, and after 3, 6, 12,
      18, and 24 months. RESULTS: No implant from either group was lost during 2 years.
      Clinical peri-implant parameters, clinical implant stability measurements, and
      marginal bone resorptions showed no statistically significant differences between
      the two groups during 24 months. CONCLUSION: The results of this clinical trial
      suggest that the early loading approach of two dental implants supporting a
      mandibular overdenture does not jeopardize peri-implant soft tissue health,
      marginal bone resorption, and implant stability.

PMID- 17209785
TI  - Plasma and gingival crevicular fluid phenytoin concentrations as risk factors for
      gingival overgrowth.
AB  - BACKGROUND: Gingival enlargement is one of the side effects associated with the
      administration of phenytoin. The mechanism by which phenytoin induces gingival
      enlargement is not well understood. This study was conducted to investigate the
      relationship between plasma and gingival crevicular fluid (GCF) phenytoin
      concentrations and the degree of gingival overgrowth in patients with similar
      gingival and plaque indices and also to determine the risk factors for gingival
      enlargement. METHODS: Eighteen patients taking phenytoin in regular doses > or =6
      months prior to the investigation participated in the study. Gingival enlargement
      was evaluated with two indices to score vertical and horizontal overgrowth. The
      gingival index (GI), plaque index (PI), gingival bleeding time index (GBTI),
      probing depth (PD), and clinical attachment level (CAL) were also evaluated. GCF
      and plasma phenytoin concentrations were determined by using high-performance
      liquid chromatography (HPLC). RESULTS: There was no significant difference
      between responders and non-responders for PD, CAL, PI, GI, and GBTI. Phenytoin
      was detected in all of the GCF and plasma samples using the HPLC analysis method.
      The mean concentration of phenytoin in GCF was significantly greater than the
      concentration of phenytoin in plasma. No significant difference was observed for
      the concentration of GCF phenytoin between responders and non-responders.
      However, the concentration of plasma phenytoin was significantly higher in
      responders than non-responders. CONCLUSION: This study showed that plasma
      phenytoin level appeared to be a risk factor for phenytoin-induced gingival
      overgrowth.

PMID- 17209786
TI  - Effects of periodontal therapy during pregnancy on periodontal status, biologic
      parameters, and pregnancy outcomes: a pilot study.
AB  - BACKGROUND: Few studies have examined the potential effects of periodontal
      treatment during pregnancy on pregnancy outcomes, periodontal status, and
      inflammatory biomarkers. METHODS: A randomized, delayed-treatment, controlled
      pilot trial was conducted to evaluate the effects of second-trimester scaling and
      root planing and the use of a sonic toothbrush on the rate of preterm delivery
      (<37 weeks gestation). Secondary outcome measures included changes in periodontal
      status, levels of eight oral pathogens, levels of gingival crevicular fluid (GCF)
      interleukin-1beta (IL-1beta), prostaglandin E(2) (PGE(2)), 8-isoprostane (8-iso),
      and IL-6, and serum levels of IL-6, soluble intercellular adhesion molecule 1
      (sICAM1), 8-isoprostane, soluble glycoprotein 130 (sGP130), IL-6 soluble receptor
      (IL-6sr), and C-reactive protein (CRP). Logistic regression models were used to
      test for effects of treatment on preterm delivery. Secondary outcomes were
      analyzed by analysis of covariance adjusting for subject baseline values.
      RESULTS: Periodontal intervention resulted in a significantly decreased incidence
      odds ratio (OR) for preterm delivery (OR = 0.26; 95% confidence interval = 0.08
      to 0.85), adjusting for baseline periodontal status which was unbalanced after
      randomization. Pregnancy without periodontal treatment was associated with
      significant increases in probing depths, plaque scores, GCF IL-1beta, and GCF IL
      6 levels. Intervention resulted in significant improvements in clinical status
      (attachment level, probing depth, plaque, gingivitis, and bleeding on probing
      scores) and significant decreases in levels of Prevotella nigrescens and
      Prevotella intermedia, serum IL-6sr, and GCF IL-1beta. CONCLUSIONS: Results from
      this pilot study (67 subjects) provide further evidence supporting the potential
      benefits of periodontal treatment on pregnancy outcomes. Treatment was safe,
      improved periodontal health, and prevented periodontal disease progression.
      Preliminary data show a 3.8-fold reduction in the rate of preterm delivery, a
      decrease in periodontal pathogen load, and a decrease in both GCF IL-1beta and
      serum markers of IL-6 response. However, further studies will be needed to
      substantiate these early findings.

PMID- 17209787
TI  - Autoantibodies directed to extracellular matrix components in patients with
      different clinical forms of periodontitis.
AB  - BACKGROUND: Periodontal disease occurs in different clinical forms, from mild and
      easily controllable to more aggressive inflammatory manifestations, with
      difficult clinical or surgical control. There is evidence that a local autoimmune
      reaction may participate in the onset and persistence of the aggressive forms of
      periodontal disease. As the underlying mechanism in this process is not fully
      understood, we decided to investigate whether patients bearing this form of
      disease presented higher levels of antibodies directed to extracellular matrix
      (ECM) components such as type I collagen, fibronectin, and laminin. METHODS:
      Three groups of patients were selected by clinical criteria: 22 subjects with
      aggressive periodontitis (AgP) = group A; 18 subjects with chronic periodontitis
      (CP) = group B; and 10 healthy (H) volunteers without periodontal disease = group
      C. Autoantibody levels were evaluated in the sera of these patients using the
      enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The levels of
      autoantibodies directed to ECM components (type I collagen, fibronectin and
      laminin) in the sera of patients with AgP and CP were shown to be statistically
      different (P <0.05). CONCLUSIONS: Although the present findings suggest an
      involvement of autoantibodies directed to ECM components per se in the pathogeny
      of certain types of periodontal disease, the available data do not support the
      classification of the lesions as autoimmune. Nevertheless, the findings open a
      possibility for the development of an additional method for a differential
      diagnosis of the aggressive forms of periodontal disease.

PMID- 17209788
TI  - Root coverage with a coronally positioned flap used in combination with enamel
      matrix derivative: 18-month clinical evaluation.
AB  - BACKGROUND: Ginigival recession can be successfully treated with coronally
      positioned flaps. Twelve-month data failed to demonstrate that topical
      application of enamel matrix derivative (EMD) used in combination with the
      coronally positioned flap enhances clinical outcomes of the surgical technique
      used alone. This study was designed to examine the effects of EMD combined with
      the coronally positioned flap over an 18-month postoperative period. METHODS:
      Thirty patients presenting with Miller Class I or II gingival recessions on
      single-rooted teeth participated in this parallel-design clinical study. Six
      weeks after phase I therapy, recession areas were surgically treated with a
      coronally positioned flap for root coverage. Teeth in the experimental group
      received EMD treatment of the exposed root, whereas control teeth did not.
      Clinical parameters evaluated at baseline and 18 months postoperatively included
      gingival recession, clinical attachment level, probing depth, and the apico
      coronal dimension of the keratinized tissue. RESULTS: Compared to baseline, 18
      month measurements showed a significant reduction in probing depth, gain in
      attachment level, and decrease in gingival recession for control and experimental
      groups. When the results of the two treatment groups were compared, the
      experimental group presented with significantly greater root coverage than the
      control group (2.66 +/- 0.61 mm versus 1.73 +/- 0.70 mm, respectively), more gain
      in clinical attachment than the control group (2.80 +/- 0.76 mm versus 2.06 +/-
      0.70 mm, respectively), and a greater gain in the apico-coronal dimension of the
      keratinized tissue than the control group (0.13 +/- 0.06 mm versus -0.06 +/- 0.01
      mm, respectively). CONCLUSION: The results of this study indicate that topical
      application of EMD is beneficial in augmenting the effects of the coronally
      positioned flap in terms of amount of root coverage, gain in clinical attachment,
      and in increasing the apico-coronal dimension of the keratinized tissue.

PMID- 17209789
TI  - Gingival crevicular fluid matrix metalloproteinase (MMP)-7, extracellular MMP
      inducer, and tissue inhibitor of MMP-1 levels in periodontal disease.
AB  - BACKGROUND: During periodontal inflammation, matrix metalloproteinases (MMPs) are
      under the control of several regulatory mechanisms including the upregulation of
      expression by inducers and downregulation by inhibitors. Our study aimed to
      examine the levels and molecular forms of MMP-7, tissue inhibitor of MMP (TIMP)
      1, and extracellular matrix metalloproteinase inducer (EMMPRIN) in gingival
      crevicular fluid (GCF) from patients with different periodontal diseases.
      METHODS: A total of 80 subjects (20 patients with generalized aggressive
      periodontitis [GAgP], 20 with chronic periodontitis [CP], 20 with gingivitis, and
      20 periodontally healthy subjects) were included in this study. Periodontal
      status was evaluated by measuring probing depth, clinical attachment loss,
      presence of bleeding on probing, and plaque. GCF MMP-7, TIMP-1, and EMMPRIN
      levels and molecular forms were analyzed by enzyme-linked immunosorbent assay
      (ELISA) and Western immunoblot techniques using specific antibodies. RESULTS:
      Total amounts of GCF MMP-7 were found to be similar between the study groups.
      GAgP, CP, and gingivitis groups had significantly higher total amounts of GCF
      EMMPRIN compared to healthy subjects (P <0.008). Among the patient groups, the
      GAgP group had the highest total amount of GCF EMMPRIN relative to the gingivitis
      group (P = 0.0004). Soluble EMMPRIN existed in GCF in multiple molecular-weight
      species especially in periodontitis-affected GCF under non-reducing conditions,
      i.e., 30-, 55-, 100-, 180-, and 200-kDa species. All patient groups had
      significantly elevated total amounts of GCF TIMP-1 relative to the healthy group
      (P <0.0001). GAgP and CP groups also had a higher total amount of GCF TIMP-1
      compared to the gingivitis group (P <0.0001 and P <0.0001, respectively). The
      GAgP group had higher GCF TIMP-1 and EMMPRIN levels compared to the CP group, but
      this elevation did not reach statistical significance. CONCLUSIONS: Our data
      indicate that MMP-7 is associated with the innate host defense in periodontal
      tissues. Increased EMMPRIN and TIMP-1 levels in GCF are associated with the
      enhanced severity of periodontal inflammation, indicating that these molecules
      can participate in the regulation of progression of periodontal diseases. To our
      knowledge, the present study demonstrated the presence of soluble forms of
      EMMPRIN in GCF of patients with different periodontal diseases for the first
      time.

PMID- 17209790
TI  - Effects of endogenous and exogenous prostaglandin E2 on the proliferation and
      differentiation of a mouse cementoblast cell line (OCCM-30).
AB  - BACKGROUND: Cementum formation is considered to be a critical event for
      successful regeneration of periodontal tissues. Cementoblasts share many
      characteristics with osteoblasts. Prostaglandin E(2) (PGE(2)) is an important
      local factor in bone metabolism. Although the effects of PGE(2) on osteoblasts
      are well known, its effects on cementoblasts have not yet been established. We
      examined the effects of PGE(2) on proliferation and differentiation in a mouse
      cementoblast cell line, OCCM-30 cells. METHODS: OCCM-30 cells were treated with
      three concentrations of PGE(2) (10, 100, and 1,000 ng/ml). Cell number, alkaline
      phosphatase (ALP) activity, and expression for mineralization-related genes were
      determined. Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa
      B (NF-kappaB) ligand (RANKL) expression were also examined by real-time
      polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The addition of PGE(2) at the highest dose used in this study suppressed
      cell proliferation of OCCM-30 cells. The expression of mineralization-related
      marker mRNA, such as type 1 collagen, ALP, bone sialoprotein (BSP), and
      osteocalcin (OCN), was constitutively detected in OCCM-30 cells. PGE(2) dose
      dependently stimulated ALP activity and BSP-mRNA expression in OCCM-30 cells at
      day 3. Transcripts for OPG and RANKL and the protein level of OPG in culture
      media were upregulated with PGE(2) stimulation. CONCLUSION: These results
      demonstrate that PGE(2) suppressed cementoblast proliferation but stimulated ALP
      activity and the BSP-mRNA level, suggesting a role of PGE(2) in controlling
      cementoblast differentiation, and further indicate that PGE(2) modulates RANKL
      and OPG expression in cementoblasts; the increase of OPG secreted from
      cementoblasts with PGE(2) stimulation may be essential to protect the root
      surface from resorption.

PMID- 17209792
TI  - Association between maternal periodontitis and an increased risk of preeclampsia.
AB  - BACKGROUND: Periodontal disease has been considered a systemic exposure
      implicated in a higher risk of adverse pregnancy outcomes. The aim of the present
      study was to determine whether maternal periodontitis is associated with an
      increased risk of preeclampsia. METHODS: A case-control study was conducted in a
      public hospital in Belo Horizonte, Brazil. During the study period, 588 women,
      aged 14 to 46 years, were deemed eligible and had data available for analysis.
      Maternal demographic and medical data were collected from medical records.
      Preeclampsia was defined as blood pressure >140/90 mm Hg and > or =1+ proteinuria
      after 20 weeks of gestation. A periodontal examination was performed postpartum.
      Maternal periodontitis was defined as the presence of four or more teeth with one
      or more sites with a probing depth > or =4 mm and clinical attachment loss > or
      =3 mm at the same site. The effects of maternal age, chronic hypertension,
      primiparity, smoking, alcohol use, and number of prenatal visits were analyzed.
      Adjusted odds ratios (ORs) for preeclampsia were calculated using multivariate
      logistic regression. RESULTS: The prevalence of periodontitis was 63.9% and
      preeclampsia was 18.5%. Variables associated with preeclampsia were chronic
      hypertension (OR = 4.10; 95% confidence interval [CI] = 2.0 to 8.4; P = 0.001),
      primiparity (OR = 2.40; 95% CI = 1.5 to 3.9; P = 0.004), maternal age (OR = 1.07;
      95% CI = 1.0 to 1.1; P = 0.001), and maternal periodontitis (OR = 1.88; 95% CI =
      1.1 to 3.0; P = 0.001). CONCLUSION: Maternal periodontitis was determined to be
      associated with an increased risk of preeclampsia.

PMID- 17209791
TI  - The influence of cyclosporin a on mechanical retention of dental implants
      previously integrated to the bone: a study in rabbits.
AB  - BACKGROUND: Immunosuppressive agents may induce severe changes on bone metabolism
      and may impair the osseointegration process during the implant healing. No data
      are available concerning the influence of cyclosporin A on dental implants
      previously integrated to the bone. The aim of this study was to evaluate the
      influence of cyclosporin A administration on the mechanical retention of bone
      previously integrated to dental implants. METHODS: Eighteen female New Zealand
      rabbits were submitted to an implant surgery. Each animal received one commercial
      dental implant of 10 x 3.75 mm. After 12 weeks of an undisturbed healing period,
      six animals were randomly sacrificed and the removal torque test was performed
      (group A). In addition, six animals were submitted to a daily injection of
      cyclosporin A in a dosage of 10 mg/kg (group C), and six animals received saline
      solution as a control (group B). After 12 weeks of cyclosporin A administration,
      groups B and C were sacrificed and submitted to a removal torque test in which
      higher values can be interpreted as higher mechanical bone retention to the
      implant surface or higher osseointegration. RESULTS: The removal torque results
      were 30.5 (+/-9.8) Ncm for group A, 50.17 (+/-17.5) Ncm for group B, and 26 (+/
      7.8) Ncm for group C. The statistical analysis showed significant differences
      between groups A and B (P <0.05) and groups B and C (P <0.01). CONCLUSION:
      Cyclosporin A administration may impair the mechanical retention of dental
      implants previously integrated to the bone.

PMID- 17209793
TI  - Postoperative complications following gingival augmentation procedures.
AB  - BACKGROUND: Postoperative pain, swelling, and bleeding are the most common
      complications following soft tissue grafting procedures; however, detailed
      documentation is sparse in the literature. The aims of this prospective study
      were as follows: 1) to compare the frequency of complication occurrence after
      free soft tissue grafting (FSTG) or subepithelial connective tissue grafting
      (SCTG) procedures; 2) to evaluate the use of an acellular dermal matrix (ADM) as
      the donor tissue alternative to an FSTG or SCTG; and 3) to identify possible
      predictors for these complications. METHODS: Seventy-five FSTG and 256 SCTG
      procedures were performed in 228 patients by a single operator. In five free soft
      tissue and 84 bilaminar graft procedures, an ADM was used instead of autogenous
      tissue. Variables such as the duration and location of procedures, smoking
      history, gender, and age were recorded. Patients were asked to fill out a
      questionnaire 1 week after the surgeries regarding postoperative pain, swelling,
      and bleeding. Data were analyzed using the chi2 test and logistic regression
      analysis. Odds ratios were calculated for moderate and severe adverse outcomes
      grouped together. RESULTS: The duration of surgical procedures was highly
      correlated with pain or swelling post-surgically (P = 0.001). Current smokers
      were three times more likely to experience post-surgical swelling (P = 0.01).
      Patients who underwent FSTG procedures were three times more likely to develop
      post-surgical pain (P = 0.002) or bleeding (P = 0.03) compared to those who
      received SCTG procedures. When an ADM was applied instead of autogenous tissue,
      the probability of swelling or bleeding was significantly reduced (odds ratio
      [OR] = 0.46, P = 0.02 and OR = 0.3, P = 0.001, respectively). CONCLUSIONS: Long
      surgical procedures and smoking may increase the severity and frequency of
      certain post-surgical complications after gingival augmentation procedures. FSTG
      procedures incur a higher likelihood for postoperative pain or bleeding than SCTG
      procedures, whereas the application of an ADM may significantly reduce the
      probability of swelling and bleeding.

PMID- 17209794
TI  - A retrospective evaluation of 1,387 single-tooth implants: a 6-year follow-up.
AB  - BACKGROUND: The aim of this study was to evaluate the overall survival rate and
      factors that affect the clinical outcome of 1,387 consecutively placed implant
      supported single restorations up to 6 years. METHODS: During 6 years (1999 to
      2005), 1,387 implants were placed in 1,215 subjects (1,073 males and 142 females)
      who required single-tooth replacements. The average time from implant placement
      was 2.7 +/- 3.27 years. Implants were mostly placed in the maxillary premolar
      area (39.5%) followed by the anterior maxillary area (28.7%). Implant survival
      and location, need for bone augmentation, and implant dimensions were recorded
      and analyzed. RESULTS: Failed implants totaled 96, resulting in an overall
      survival rate of 93.1%. The vast majority of failures (94.8%) occurred during the
      first year following implant placement. Bone augmentation was performed in 9.7%
      of the implants with a 92.5% survival rate, similar to the survival rate of non
      augmented areas (93.1%; P = 0.79). The average implant length was 13.3 mm,
      ranging from 8 to 16 mm. Longer implants (> or =11 mm) showed similar survival
      rates as implants <11 mm (93.2% versus 90.2%, respectively; P = 0.4). Implant
      width ranged between 3.25 to 5 mm (mean 3.9), with no effect on implant survival
      (P = 0.43). There was a significant difference in implant survival according to
      the anatomic zone of implant placement (P = 0.0075). The maxillary premolar area
      showed the highest survival rate (96.2%). CONCLUSION: Implant-supported single
      tooth replacement is a predictable procedure with good survival rates up to 6
      years.

PMID- 17209795
TI  - The potential prognostic value of some periodontal factors for tooth loss: a
      retrospective multilevel analysis on periodontal patients treated and maintained
      over 10 years.
AB  - BACKGROUND: The great challenge in clinical periodontology is assigning a
      prognosis to a periodontally affected patient. Many different factors can affect
      the long-term maintenance of periodontally compromised teeth. The main questions
      usually considered by the periodontist are: 1) Will a tooth lose more bone in the
      future? 2) Will the tooth itself be lost in the future? The purpose of this
      retrospective study was to evaluate the value of some clinical, genetic, and
      radiographic variables in predicting tooth loss in periodontal patients (aged 40
      to 60 years) treated and maintained for 10 years. METHODS: Sixty consecutive non
      smoking patients (aged 46.77 +/- 4.96 years) with moderate to severe chronic
      periodontitis (CP) were treated with scaling and root planing (SRP). Some
      patients also underwent additional surgical treatments. All patients were
      maintained in the same private practice for 10 years. The frequency of recall
      appointments was 3.4 +/- 1.0 months. At baseline (T(0)) and 10 years later (T(2))
      the following clinical variables were evaluated: the number of teeth, probing
      depths (PD), tooth mobility (TM), and presence of prosthetic restorations (PR).
      In addition, radiographic measurements were taken of the mesial and distal
      distances from the cemento-enamel junction (CEJ) to the bottom of the defect
      (BD), to the bone crest (BC), and to the root apex (RA). At T(2), a genetic test
      to determine the IL-1 genotype and genetic susceptibility for severe periodontal
      disease was performed for all 60 patients, and they were classified as IL-1
      genotype positive (G+) or negative (G-) according to the test results. Tooth loss
      was used as the outcome variable. Different predictor variables were then tested
      using a two-level statistical model (patient and tooth levels). At the patient
      level, these were: age, gender, mean bone loss (mean CEJ-BD)(T0), the interleukin
      1 (IL-1) genotype, the interaction between mean bone loss, and IL-1 genotype
      (mean CEJ-BD(T0) x IL-1 genotype). At the tooth level, the variables were:
      TM(T0), prosthetic restorations (PR)(T0), molar teeth (MT)(T0), the infrabony
      component of the defect (BC-BD)(T0), PD(T0), bone level (CEJ-BD)(T0), and
      residual supporting bone (BD-RA)(T0). RESULTS: Among the considered predictor
      variables, the following were significantly associated with the outcome variable:
      1) MT(T0) (P <0.0001); 2) BC-BD(T0) (P = 0.0377); and 3) BD-RA(T0) (P <0.0001).
      MT(T0) were found to be more prone to loss and the amount of BD-RA(T0) prognostic
      for tooth loss: the lower the residual amount of supporting bone, the higher the
      probability of tooth loss. Conversely, the BC-BD(T0)was associated with a reduced
      probability of future tooth loss: the greater the infrabony component, the lower
      the probability of tooth loss. None of the other considered predictors proved
      predictive for tooth loss. CONCLUSIONS: Within the scope of this study, many
      traditional prognostic factors were ineffective in predicting future tooth loss
      and, therefore, were of no prognostic value. Conversely, a few specific factors
      at the tooth level emerged as viable prognostic factors. The use of these factors
      may be of great value to practitioners as predictors of tooth loss when assigning
      a prognosis.

PMID- 17209796
TI  - Atrophic glossitis from vitamin B12 deficiency: a case misdiagnosed as burning
      mouth disorder.
AB  - BACKGROUND: Glossodynia, or painful sensation of the tongue, can have a spectrum
      of etiologies, such as local infection, trauma, nerve damage, glossitis, or the
      enigmatic neuropathic pain syndrome, burning mouth disorder (BMD; also known as
      burning mouth syndrome). Careful history-taking, physical examination, and
      appropriate laboratory screening can differentiate these causes of glossodynia
      and direct further therapy. METHODS: A 73-year-old woman presented with several
      months of glossodynia having previously been diagnosed by her primary care
      physician with primary BMD. Subsequently, she consulted an otolaryngologist, who
      pursued further diagnostic evaluation. RESULTS: Examination revealed the presence
      of a beefy, red, smooth tongue, and further laboratory evaluation yielded a low
      serum vitamin B(12) level and macrocytosis. Three months of oral vitamin B(12)
      supplementation led to partial restoration of serum vitamin B(12) levels and a
      modest improvement in symptoms. Her final diagnoses were atrophic glossitis and
      glossodynia secondary to vitamin B(12) deficiency, most likely due to pernicious
      anemia. CONCLUSIONS: The results of this case have important clinical
      implications for the diagnostic evaluation and management of patients with
      glossodynia and apparent BMD. Pathogenic mechanisms of nutrient deficiency in
      atrophic glossitis are discussed.

PMID- 17209797
TI  - Enhancing the regenerative potential of guided tissue regeneration to treat an
      intrabony defect and adjacent ridge deformity by orthodontic extrusive force.
AB  - BACKGROUND: The biologic potential of the periodontal ligament (PDL) can be
      harnessed to solve complex clinical problems involving several dental
      disciplines. The purpose of this case report is to demonstrate that orthodontic
      extrusive force can enhance the regenerative potential of guided tissue
      regeneration (GTR) to eliminate an intrabony defect and augment a ridge
      deformity. METHODS: Regenerative therapy by open debridement with particulate
      anorganic cancellous bovine-derived bone xenograft (BDX), bioabsorbable membrane,
      and minocycline root conditioning was carried out. Eight weeks after the initial
      surgery, orthodontic extrusion and uprighting simultaneously were initiated.
      RESULTS: Radiographs and reentry documentation demonstrated that orthodontic
      extrusive force could enhance the regenerative potential of GTR. Consequently,
      the intrabony defect and alveolar ridge were successfully treated. CONCLUSION:
      This case report demonstrates that orthodontic-regenerative combined therapy can
      resolve complex clinical problems involving several dental disciplines.

PMID- 17209798
TI  - Light regulation of stomatal movement.
AB  - Stomatal pores, each surrounded by a pair of guard cells, regulate CO2 uptake and
      water loss from leaves. Stomatal opening is driven by the accumulation of K+
      salts and sugars in guard cells, which is mediated by electrogenic proton pumps
      in the plasma membrane and/or metabolic activity. Opening responses are achieved
      by coordination of light signaling, light-energy conversion, membrane ion
      transport, and metabolic activity in guard cells. In this review, we focus on
      recent progress in blue- and red-light-dependent stomatal opening. Because the
      blue-light response of stomata appears to be strongly affected by red light, we
      discuss underlying mechanisms in the interaction between blue-light signaling and
      guard cell chloroplasts.

PMID- 17209799
TI  - Non-nicotinic therapies for smoking cessation.
AB  - Cigarette smoking is the primary cause of numerous preventable diseases; as such,
      the goals of smoking cessation are both to reduce health risks and to improve the
      quality of life. Currently, the first-line smoking cessation therapies include
      nicotine replacement products and bupropion. The nicotinic receptor partial
      agonist varenicline has recently been approved by the FDA for smoking cessation.
      A newer product currently under development and seeking approval by the FDA are
      nicotine vaccines. Clonidine and nortriptyline have demonstrated some efficacy
      but side effects may limit their use to second-line therapeutic products. Other
      therapeutic drugs that are under development include rimonabant, mecamylamine,
      monoamine oxidase inhibitors, and dopamine receptor D3 antagonists. Inhibitors of
      nicotine metabolism are also promising candidates for smoking reduction and
      cessation. In conclusion, promising new therapeutic products are emerging and
      they will provide smokers additional options to assist in achieving smoking
      cessation.

PMID- 17209800
TI  - Circadian rhythms: mechanisms and therapeutic implications.
AB  - The mammalian circadian system is organized in a hierarchical manner in that a
      central pacemaker in the suprachiasmatic nucleus (SCN) of the brain's
      hypothalamus synchronizes cellular circadian oscillators in most peripheral body
      cells. Fasting-feeding cycles accompanying rest-activity rhythms are the major
      timing cues in the synchronization of many, if not most, peripheral clocks,
      suggesting that the temporal coordination of metabolism and proliferation is a
      major task of the mammalian timing system. The inactivation of noxious food
      components by hepatic, intestinal, and renal detoxification systems is among the
      metabolic processes regulated in a circadian manner, with the understanding of
      the involved clock output pathways emerging. The rhythmic control of xenobiotic
      detoxification provides the molecular basis for the dosing time-dependence of
      drug toxicities and efficacy. This knowledge can in turn be used in improving or
      designing chronotherapeutics for the patients who suffer from many of the major
      human diseases.

PMID- 17209801
TI  - New insights into the mechanism of action of amphetamines.
AB  - Amphetamine is a psychostimulant commonly used to treat several disorders,
      including attention deficit, narcolepsy, and obesity. Plasmalemmal and vesicular
      monoamine transporters, such as the neuronal dopamine transporter and the
      vesicular monoamine transporter-2, are two of its principal targets. This review
      focuses on new insights, obtained from both in vivo and in vitro studies, into
      the molecular mechanisms whereby amphetamine, and the closely related compounds
      methamphetamine and methylenedioxymethamphetamine, cause monoamine, and
      particularly dopamine, release. These mechanisms include amphetamine-induced
      exchange diffusion, reverse transport, and channel-like transport phenomena as
      well as the weak base properties of amphetamine. Additionally, amphetamine
      analogs may affect monoamine transporters through phosphorylation, transporter
      trafficking, and the production of reactive oxygen and nitrogen species. All of
      these mechanisms have potential implications for both amphetamine- and
      methamphetamine-induced neurotoxicity, as well as dopaminergic neurodegenerative
      diseases.

PMID- 17209802
TI  - Oxidative stress, antioxidant status and DNA damage in patients with impaired
      glucose regulation and newly diagnosed Type 2 diabetes.
AB  - Previous studies have postulated the association between oxidative stress and
      Type 2 diabetes. Considering the long pre-diabetic period with IGR (impaired
      glucose regulation) and its high risk of developing diabetes, to test this
      hypothesis, we have investigated oxidative stress pathways and DNA damage in
      patients with IGR and newly diagnosed Type 2 diabetes. The study population
      consisted of 92 subjects with NGT (normal glucose tolerance), 78 patients with
      IGR and 113 patients with newly diagnosed diabetes. Plasma MDA (malondialdehyde)
      and TAC (total antioxidative capacity) status, erythrocyte GSH content and SOD
      (superoxide dismutase) activity were determined. A comet assay was employed to
      evaluate DNA damage. Compared with subjects with NGT, patients with IGR had
      reduced erythrocyte SOD activity. Patients with diabetes had a higher plasma MDA
      concentration, but a lower plasma TAC level and erythrocyte SOD activity, than
      the NGT group. Correlation analysis revealed a strong positive association
      between IR (insulin resistance) and MDA concentration, but negative correlations
      with TAC status and SOD activity. With respect to beta-cell function, a positive
      association with TAC status and an inverse correlation with GSH respectively,
      were observed. The comet assay revealed slight DNA damage in patients with IGR,
      which was increased in patients with diabetes. Significant correlations were
      observed between DNA damage and hyperglycaemia, IR and beta-cell dysfunction. In
      conclusion, the results of the present study suggest that hyperglycaemia in an
      IGR state caused the predominance of oxidative stress over antioxidative defence
      systems, leading to oxidative DNA damage, which possibly contributed to
      pancreatic beta-cell dysfunction, IR and more pronounced hyperglycaemia. This
      vicious circle finally induced the deterioration to diabetes.

PMID- 17209803
TI  - New insight into the biochemical mechanisms regulating auxin transport in plants.
AB  - The transport of the plant hormone auxin has been under intense investigation
      since its identification 80 years ago. Studies have gradually refined our
      understanding of the importance of auxin transport in many aspects of plant
      signalling and development, and the focus has intensified in recent years towards
      the identification of the proteins involved in auxin transport and their
      functional mechanism. Within the past 18 months, the field has progressed
      rapidly, with confirmation that several distinct classes of proteins, previously
      dubbed as 'putative auxin permeases' or 'auxin transport facilitators', are bona
      fide transporters of IAA (indol-3-ylacetic acid). In this review we will appraise
      the recent transport data and highlight likely future research directions,
      including the characterization of auxiliary proteins necessary for the regulation
      of auxin transporters.

PMID- 17209805
TI  - The plastome-encoded PsaJ subunit is required for efficient Photosystem I
      excitation, but not for plastocyanin oxidation in tobacco.
AB  - The functions of several small subunits of the large photosynthetic multiprotein
      complex PSI (Photosystem I) are not yet understood. To elucidate the function of
      the small plastome-encoded PsaJ subunit, we have produced knockout mutants by
      chloroplast transformation in tobacco (Nicotiana tabacum). PsaJ binds two
      chlorophyll-a molecules and is localized at the periphery of PSI, close to both
      the Lhca2- and Lhca3-docking sites and the plastocyanin-binding site. Tobacco
      psaJ-knockout lines do not display a visible phenotype. Despite a 25% reduction
      in the content of redox-active PSI, neither growth rate nor assimilation capacity
      are altered in the mutants. In vivo, redox equilibration of plastocyanin and PSI
      is as efficient as in the wild-type, indicating that PsaJ is not required for
      fast plastocyanin oxidation. However, PsaJ is involved in PSI excitation: altered
      77 K chlorophyll-a fluorescence emission spectra and reduced accumulation of
      Lhca3 indicate that antenna binding and exciton transfer to the PSI reaction
      centre are impaired in DeltapsaJ mutants. Under limiting light intensities,
      growth of DeltapsaJ plants is retarded and the electron-transport chain is far
      more reduced than in the wild-type, indicating that PSI excitation might limit
      electron flux at sub-saturating light intensities. In addition to defining in
      vivo functions of PsaJ, our data may also have implications for the
      interpretation of the crystal structure of PSI.

PMID- 17209804
TI  - Structural and functional analysis of the Na+/H+ exchanger.
AB  - The mammalian NHE (Na+/H+ exchanger) is a ubiquitously expressed integral
      membrane protein that regulates intracellular pH by removing a proton in exchange
      for an extracellular sodium ion. Of the nine known isoforms of the mammalian
      NHEs, the first isoform discovered (NHE1) is the most thoroughly characterized.
      NHE1 is involved in numerous physiological processes in mammals, including
      regulation of intracellular pH, cell-volume control, cytoskeletal organization,
      heart disease and cancer. NHE comprises two domains: an N-terminal membrane
      domain that functions to transport ions, and a C-terminal cytoplasmic regulatory
      domain that regulates the activity and mediates cytoskeletal interactions.
      Although the exact mechanism of transport by NHE1 remains elusive, recent studies
      have identified amino acid residues that are important for NHE function. In
      addition, progress has been made regarding the elucidation of the structure of
      NHEs. Specifically, the structure of a single TM (transmembrane) segment from
      NHE1 has been solved, and the high-resolution structure of the bacterial Na+/H+
      antiporter NhaA has recently been elucidated. In this review we discuss what is
      known about both functional and structural aspects of NHE1. We relate the known
      structural data for NHE1 to the NhaA structure, where TM IV of NHE1 shows
      surprising structural similarity with TM IV of NhaA, despite little primary
      sequence similarity. Further experiments that will be required to fully
      understand the mechanism of transport and regulation of the NHE1 protein are
      discussed.

PMID- 17209806
TI  - Screening and mutagenesis of a novel Bacillus pumilus strain producing alkaline
      protease for dehairing.
AB  - AIMS: To characterize and optimize a novel Bacillus pumilus strain isolated from
      biological waste which produces protease with excellent dehairing effect. This
      newly isolated strain could be utilized in the industrial leather dehairing
      process. METHODS AND RESULTS: Bacterial strains secreting proteases were screened
      from biological wastes. Positive clones were further characterized by analysing
      their efficacy in dehairing and effects on collagen integrity. Among 171 colonies
      tested, a strain BA06, identified as B. pumilus, was picked owing to its
      efficient dehairing capabilities with minimal impact on collagen. By combined
      mutagenesis using UV, N-methyl-N'-nitro-N-nitrosdguanidine and Co(60)-gamma-rays,
      this strain was further improved with regard to its alkaline protease production.
      The alkaline protease activity of the mutant strain SCU11was greatly improved up
      to 6000 U ml(-1), in comparison with its parent strain BA06 of 1200 U ml(-1).
      CONCLUSIONS: By using screening and mutagenesis methods, we have successfully
      created a B. pumilus strain that can produce high levels of alkaline proteases
      that are able to efficiently remove hair from skin with minimal damage on the
      collagen. SIGNIFICANCE AND IMPACT OF THE STUDY: This strain could be used in
      commercial alkaline protease production for leather dehairing.

PMID- 17209807
TI  - Metal-chelating compounds produced by ectomycorrhizal fungi collected from pine
      plantations.
AB  - AIMS: To investigate the in vitro production of metal-chelating compounds by
      ectomycorrhizal fungi collected from pine plantations in southern Chile. METHODS
      AND RESULTS: Scleroderma verrucosum, Suillus luteus and two isolates of
      Rhizopogon luteolus were grown in solid and liquid modified Melin-Norkans (MMN)
      media with and without iron addition and the production of iron-chelating
      compounds was determined by Chrome Azurol S (CAS) assay. The presence of
      hydroxamate and catecholate-type compounds and organic acids was also
      investigated in liquid medium. All isolates produced iron-chelating compounds as
      detected by CAS assay, and catecholates, hydroxamates as well as oxalic, citric
      and succinic acids were also detected in all fungal cultures. Scleroderma
      verrucosum produced the greatest amounts of catecholates and hydroxamates whereas
      the highest amounts of organic acids were detected in S. luteus. Nevertheless,
      the highest catecholate, hydroxamate and organic acid concentrations did not
      correlate with the highest CAS reaction which was observed in R. luteolus (Yum
      isolate). CONCLUSIONS: Ectomycorrhizal fungi produced a variety of metal
      chelating compounds when grown in liquid MMN medium. However, the addition of
      iron to all fungi cultures reduced the CAS reaction, hydroxamate and organic acid
      concentrations. Catecholate production was affected differently by iron,
      depending on the fungal isolate. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      ectomycorrhizal fungi described in this study have never been reported to produce
      metal-chelating compound production. Moreover, apart from some wood-rotting
      fungi, this is the first evidence of the presence of catecholates in R. luteolus,
      S. luteus and S. verrucosum cultures.

PMID- 17209808
TI  - Optimization for high-density cultivation of heterotrophic Chlorella based on a
      hybrid neural network model.
AB  - AIMS: The purpose of this study was to develop a reliable hybrid neural network
      (HNN) model for heterotrophic growth of Chlorella, based on which optimization
      for fed-batch (FB) cultivation of Chlorella may be successfully realized. METHODS
      AND RESULTS: Deterministic kinetic model was preliminarily developed for the
      optimization of FB cultivation of Chlorella. The highest biomass concentration
      and the maximum productivity were obtained as: 104.9 g l(-1) dry cell weight and
      0.613 g l(-1) h(-1), respectively. After several cultivations had been performed,
      an HNN model was developed. The efficiency of biomass production was further
      increased by the optimization using this model. The highest biomass concentration
      and the maximum productivity attained was: 116.2 g l(-1) dry cell weight and
      1.020 g l(-1) h(-1), respectively. CONCLUSION: The HNN model agreed well with
      experimental results in different cultivations. Comparison between the HNN model
      and the deterministic model showed that the former had better generalization
      ability, which made it a reliable tool in modelling and optimization.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The high cell density and productivity of
      biomass obtained in this study is of significance for the commercial cultivation
      of Chlorella. The simple and efficient optimization strategy proposed in this
      paper may be employed in heterotrophic mass culture of Chlorella as well as other
      similar organisms.

PMID- 17209809
TI  - Detection of genetic diversity by pulsed-field gel electrophoresis among
      Escherichia coli O157 isolated from bovine faecal samples by immunomagnetic
      separation technique.
AB  - AIMS: Escherichia coli O157 is considered to be one of most important human
      pathogens of animal origin which causes serious clinical complications. One of
      the most common methods to isolate E. coli O157 is the immunomagnetic separation
      (IMS) technique which employs specific antibodies coupled to magnetic beads to
      bind and extract cells from enrichment broths followed by plating onto sorbitol
      MacConkey agar supplemented with cefixime and potassium tellurite (CT-SMAC)
      plates. The aim of this study was to determine strain variation by pulsed-field
      gel electrophoresis (PFGE) among E. coli O157 on IMS/CT-SMAC plates. METHODS AND
      RESULTS: Every suspect colony of E. coli O157 was tested following isolation by
      the IMS/CT-SMAC technique. From 124 colonies detected; six XbaI-PFGE profiles
      were identified. CONCLUSIONS: Our results demonstrate that mixed populations of
      E. coli O157 with distinguishable PFGE profiles that are simultaneously present
      in bovine faeces can be isolated with IMS/CT-SMAC technique. SIGNIFICANCE AND
      IMPACT OF THE STUDY: If the aim of the study was to analyse diversity of PFGE
      profiles of E. coli O157 in a faecal sample following isolation by the IMS/CT
      SMAC technique, at least five colonies per sample should be analysed to detect
      different PFGE subtypes if present.

PMID- 17209810
TI  - A capillary polymerase chain reaction for Salmonella detection from poultry meat.
AB  - AIMS: In this study, a capillary polymerase chain reaction (cPCR) was applied for
      Salmonella detection from poultry meat. METHODS AND RESULTS: Salmonella detection
      limits of the optimized cPCR were determined with DNA templates from the samples
      of tetrathionate broth (TTB), Rappaport Vassiliadis broth (RVB) and selenite
      cystine broth (SCB) artificially contaminated with 10-fold dilutions of 6 x 10(8)
      CFU ml(-1) of pure Salmonella enterica ssp. enterica serovar Enteritidis 64K
      stock culture. Detection limits of cPCR from TTB, RVB and SCB were found as 6, 6
      x 10(1) and 6 x 10(4) CFU ml(-1), respectively. In addition, detection limits of
      bacteriology were also determined as 6 CFU ml(-1) with TTB and SCB, and 6 x 10(1)
      CFU ml(-1) with RVB. A total of 200 samples, consisting of 100 chicken and 100
      turkey meat samples, were tested with optimized cPCR and bacteriology. Eight and
      six per cent of the chicken meat samples were found to harbour Salmonella by cPCR
      and standard bacteriology, respectively. Of six Salmonella isolates, four
      belonged to serogroup D, two to serogroup B. CONCLUSIONS: The TTB cultures of
      both artificially and naturally contaminated samples were found to be superior to
      those of RVB and SCB cultures in their cPCR results. This cPCR, utilizing
      template from 18-h TTB primary enrichment broth culture, takes approximately 40
      min in the successful detection of Salmonella from poultry meat. SIGNIFICANCE AND
      IMPACT OF THE STUDY: This study shows that cPCR from TTB enrichment culture of
      poultry meat would enable rapid detection of Salmonella in laboratories with low
      sample throughput and limited budget.

PMID- 17209811
TI  - Patulin accumulation in apples by Penicillium expansum during postharvest stages.
AB  - AIMS: The aim of this study was to assess the opportunities of Penicillium
      expansum to develop and produce patulin in apples during cold storage and in the
      steps prior to processing of apple products. METHODS AND RESULTS: Two lots of
      apples var. Golden with different ripeness degree were used. Half of each lot was
      fungicide treated. Apples were inoculated with P. expansum and stored at 1
      degrees C for 6 weeks. The extent of lesions and patulin accumulation both at the
      end of cold storage and after 3 days at 20 degrees C were assessed. Short storage
      at 20 degrees C aimed to simulate the transport and storage steps at room
      temperature before processing. Lesion size significantly increased during the
      storage at 20 degrees C. An interaction between fungicide treatment and ripeness
      degree was found; efficiency of fungicide treatment was higher for ripe apples.
      Although lesions were evident after cold storage, no patulin was detected.
      Patulin was detected only when fruits were further stored at 20 degrees C.
      Neither ripeness degree nor fungicide treatment affected patulin accumulation.
      CONCLUSIONS: Cold storage periods of 6 weeks do not lead to patulin accumulation.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Shortening preprocessing times at warm
      temperatures would result into a reduction in patulin content at initial steps of
      fruits entering the processing plants.

PMID- 17209812
TI  - Antifungal activity of thyme (Thymus vulgaris L.) essential oil and thymol
      against moulds from damp dwellings.
AB  - AIMS: To characterize antifungal activities of essential oil of thyme (Thymus
      vulgaris L.) and pure thymol, as comparative substance, on different mould
      species isolated from damp dwellings. METHODS AND RESULTS: Fifty samples of wall
      scrapes were collected from damp dwellings in Zagreb, the capital of Croatia. The
      members of the following mould genera were recovered from the samples:
      Aspergillus (44%), Penicillium (18%) Alternaria, Ulocladium, Absidia and Mucor
      (8%) Cladosporium, Trichoderma and Rhizopus (6%), and Chaetomium (2%). Two
      strains of Stachybotrys chartarum were isolated from damp dwellings in Slovakia.
      Antifungal activities of the thyme essential oil, which contains p-cymene
      (36.5%), thymol (33.0%) and 1,8-cineole (11.3%) as main components, and pure
      thymol were determined by the dilution method and exposure to vaporous phase of
      the oil. Minimum inhibitory concentrations (MIC) of both thymol and essential oil
      were bellow 20 microg ml(-1), except for Mucor spp. (50.20 microg ml(-1)). Thymol
      exhibited approximately three-times stronger inhibition than essential oil of
      thyme. The vaporous phase of the thyme essential oil (82 microg l(-1)) in glass
      chambers strongly suppressed the sporulation of moulds during 60 days of
      exposure. CONCLUSION: The thyme essential oil possesses a wide range spectrum of
      fungicidal activity. The vaporous phase of the oil exhibited long-lasting
      suppressive activity on moulds from damp dwellings. SIGNIFICANCE AND IMPACT OF
      THE STUDY: Essential oil of thyme and thymol could be used for disinfection of
      mouldy walls in the dwellings in low concentration.

PMID- 17209813
TI  - Application of cross-linked enzyme aggregates of Bacillus badius penicillin G
      acylase for the production of 6-aminopenicillanic acid.
AB  - AIMS: Optimization of 6-aminopenicillanic acid (6-APA) production using cross
      linked enzyme aggregates (CLEA) of Bacillus badius penicillin G acylase (PAC).
      METHODS AND RESULTS: CLEA-PAC was prepared using purified/partially purified PAC
      with phenylacetic acid as active-site blocking agent and glutaraldehyde as cross
      linker. Conversion of penicillin G to 6-APA by CLEA-PAC was optimized using
      response surface methodology (RSM) (central composite rotatable design)
      consisting of a three-factor-two-level pattern with 20 experimental runs.
      CONCLUSION: Nearly, 80% of immobilization yield was obtained when partially
      purified enzyme was used for the preparation of CLEA-PAC. Quantitative conversion
      of penicillin G to 6-APA was observed within 60 min and the CLEA-PAC was reusable
      for 20 repeated cycles with 100% retention of enzyme activity. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The faster conversion of penicillin G to 6-APA by CLEA-PAC
      and efficient reusability holds a strong potential for the industrial
      application.

PMID- 17209814
TI  - Toluene-induced accumulation of trehalose by Pseudomonas sp. BCNU 106 through the
      expression of otsA and otsB homologues.
AB  - AIM: The objective of this study was to investigate toluene-induced accumulation
      mechanism of trehalose in a toluene-tolerant bacterium Pseudomonas sp. BCNU 106.
      METHODS AND RESULTS: The accumulation of trehalose by a toluene-tolerant
      bacterium Pseudomonas sp. BCNU 106 was examined at various cultivation time by
      measuring the total intracellular trehalose content, trehalase activity and mRNA
      levels of the trehalose-biosynthetic genes. The pattern of trehalose accumulation
      corresponded to the mRNA expression pattern of the trehalose-biosynthetic genes
      with the maximum level at 12 h or 4 h of cultivation with 10% (v/v) toluene,
      respectively. The trehalose-biosynthetic genes were also cloned and sequenced.
      Furthermore, the effects of toluene addition on the intracellular osmotic
      pressure and pH were investigated. It was shown that homeostasis was maintained
      in the bacterial cells. CONCLUSIONS: In a toluene-tolerant bacterium Pseudomonas
      sp. BCNU 106, a significant amount of trehalose was accumulated through the
      toluene-induced expression of the trehalose-biosynthetic genes after the exposure
      to toluene. SIGNIFICANCE AND IMPACT OF THE STUDY: The accumulation of the high
      level of intracellular trehalose was preceded by the expression of otsA/B genes
      in toluene-tolerant bacteria, contributing to the elucidation of the tolerance
      mechanism.

PMID- 17209815
TI  - Mutation in the edd gene encoding the 6-phosphogluconate dehydratase of
      Pseudomonas chlororaphis O6 impairs root colonization and is correlated with
      reduced induction of systemic resistance.
AB  - AIMS: The primary objective of this study was to determine the role of 6
      phosphogluconate dehydratase in root colonization and the induction of systemic
      resistance by the rhizobacterium, Pseudomonas chlororaphis O6. METHODS AND
      RESULTS: The edd gene encoding for 6-phosphogluconate dehydratase, which is one
      of the key enzymes in glucose utilization, was cloned. Transcription of the gene
      was higher in medium containing sugars than with organic acids. An edd mutant
      failed to grow on glucose but grew on organic acids. The edd mutant colonized
      tobacco roots at wild-type levels early after inoculation, but levels were lower
      by 12 days. The edd mutant failed to induce the systemic resistance in tobacco to
      a soft-rot pathogen at wild-type level. CONCLUSIONS: 6-Phosphogluconate
      dehydratase in P. chlororaphis O6 contributes to root colonization and induction
      of systemic resistance presumably as the consequence of its essential role in the
      Entner-Doudoroff (ED) pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: Metabolism
      of sugars through the ED pathway in P. chlororaphis O6 may be important because
      it facilitates the production of inducers of systemic resistance including
      butanediol.

PMID- 17209816
TI  - Vanillin production from simple phenols by wine-associated lactic acid bacteria.
AB  - AIMS: The ability of lactic acid bacteria (LAB) to metabolize certain phenolic
      precursors to vanillin was investigated. METHODS AND RESULTS: Gas chromatography
      mass spectrometry (GC-MS) or HPLC was used to evaluate the biosynthesis of
      vanillin from simple phenolic precursors. LAB were not able to form vanillin from
      eugenol, isoeugenol or vanillic acid. However Oenococcus oeni or Lactobacillus
      sp. could convert ferulic acid to vanillin, but in low yield. Only Lactobacillus
      sp. or Pediococcus sp. strains were able to produce significant quantities of 4
      vinylguaiacol from ferulic acid. Moreover, LAB reduced vanillin to the
      corresponding vanillyl alcohol. CONCLUSIONS: The transformation of phenolic
      compounds tested by LAB could not explain the concentrations of vanillin observed
      during LAB growth in contact with wood. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Important details of the role of LAB in the conversion of phenolic compounds to
      vanillin have been elucidated. These findings contribute to the understanding of
      malolactic fermentation in the production of aroma compounds.

PMID- 17209817
TI  - Contamination of pine nuts by fumonisin produced by strains of Fusarium
      proliferatum isolated from Pinus pinea.
AB  - AIMS: To test the ability of Fusarium proliferatum strains isolated from Pinus
      pinea to synthesize fumonisin B(1) (FB(1)) in pine nuts. METHOD AND RESULTS:
      Eleven strains were inoculated in moist sterile shelled pine nuts and whole pine
      nuts, and incubated for 28 days. Moist sterile maize was inoculated in parallel
      as an optimum substrate for FB(1) production by Fusarium species. CONCLUSIONS:
      Six of the strains produced FB(1) in shelled pine nuts, and two of them did so in
      whole pine nuts. IMPACT AND SIGNIFICANCE OF THE STUDY: F. proliferatum is able to
      grow and produce FB(1) in the husk of pine nuts and the mycotoxin can be found in
      the nut once shelled. Consequently, FB(1) may be an important hazard in pine
      nuts.

PMID- 17209818
TI  - The enumeration of chlorine-injured Escherichia coli and Enterococcus faecalis is
      enhanced under conditions where reactive oxygen species are neutralized.
AB  - AIM: To investigate the effect of neutralization of reactive oxygen species (ROS
      neutralized conditions) on the enumeration of chlorine-injured Escherichia coli
      and Enterococcus faecalis using selective and nonselective media. METHODS: Pure
      cultures of E. coli NCTC8912 and Ent. faecalis NCTC775 were injured using dilute
      sodium hypochlorite, at free chlorine levels of 0.6 and 0.9 microg ml(-1),
      respectively, and then enumerated at 37 degrees C by surface plate counts on
      nonselective nutrient (N) agar and on several selective media, either under (i)
      standard aerobic conditions; (ii) aerobic conditions using growth medium,
      supplemented with 0.05%-w/v sodium pyruvate, to neutralize peroxides; or (iii)
      conditions designed to neutralize ROS, using a combination of 0.05%-w/v sodium
      pyruvate in the growth medium, together with incubation in an anaerobic jar.
      RESULTS: The counts obtained on the nonselective medium were lowest under aerobic
      conditions in unsupplemented medium, higher in pyruvate-supplemented (peroxide
      neutralized) medium and highest for ROS-neutralized conditions. Counts for the
      selective media were often lower than those for nonselective N (nutrient) agar,
      with enhancement under peroxide-neutralized conditions and a further increase in
      counts under ROS-neutralized conditions. Broadly similar observations were made
      for three other strains of each organism. CONCLUSIONS: Chlorine-injured E. coli
      and Ent. faecalis become sensitive to ROS, giving higher counts under ROS
      neutralized enumeration conditions than under conventional aerobic conditions.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The enhancement in counts observed under
      ROS-neutralized conditions indicate that the addition of pyruvate to the growth
      medium may not fully counteract the effects of sublethal injury under aerobic
      conditions, which is a novel observation. Thus, ROS-neutralized conditions may be
      required for optimal enumeration of faecal indicator bacteria. Furthermore, the
      lower counts, obtained using selective media indicate that the sensitivity of
      chlorine-injured bacteria to selective agents is not necessarily reversed under
      ROS-neutralized conditions.

PMID- 17209819
TI  - Factors involved in binding of Lactobacillus plantarum Lp6 to rat small
      intestinal mucus.
AB  - AIM: To investigate the adhesion determinants of Lactobacillus plantarum Lp6, a
      dairy isolate. METHODS AND RESULTS: Small intestinal mucus extracted from rats
      was used as a substrate for adhesion. Adhesion determinants were studied by
      physical, chemical and enzymatic pretreatments of the bacteria, and adhesion
      inhibition assay. The mannose-specific adhesins were explored by studying the
      effect of d-mannose on adhesion and the yeast-agglutinating ability of the
      bacteria. It was found that adhesion decreased after bacteria were treated with
      sodium metaperiodate, protease K, trypsin, lithium chloride and trichloroacetic
      acid. However, adhesion did not decrease after trypsin-treated bacteria were
      incubated with cell surface protein extract. Cell surface bound
      exopolysaccharides were found to inhibit the adhesion. D-mannose inhibited the
      adhesion in a dose-dependent manner. The bacteria could significantly agglutinate
      yeast and lost this ability after protease K treatment. CONCLUSIONS: Adhesion was
      mainly mediated by the mannose specific adhesins, which might be proteins that
      reversibly bind to the cell surface components. Cell surface-bound
      exopolysaccharides were also involved in adhesion. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The mannose-specific adhesion of Lact. plantarum Lp6 to rat mucus might be
      important for competing with pathogens-binding sites in gut, which may be used to
      resist the colonization of the pathogens.

PMID- 17209820
TI  - Antimicrobial resistance of Listeria spp. recovered from processed bison.
AB  - AIMS: The current study examined the antimicrobial susceptibility of 86 Listeria
      spp. isolated from processed bison carcasses. MATERIALS AND METHODS:
      Susceptibility to 25 antimicrobial agents was determined using E-test and
      National Antimicrobial Resistance Monitoring System (NARMS) panels. Most Listeria
      isolates (88-98%) exhibited resistance to bacitracin, oxacillin, cefotaxime, and
      fosfomycin. Resistance to tetracycline (18.6%) was also common. Of the 16
      tetracycline-resistant Listeria isolates, 15 carried tetM and 2 contained
      integrase of Tn1545 transposons. Rifampicin and trimethoprim-sulfamethoxazole
      were the most active antimicrobial agents against Listeria spp., with a MIC(90)
      of 0.38 microg ml(-1). Ampicillin, erythromycin, penicillin, gentamicin, and
      tobramycin also exhibited good activity against Listeria spp., with MIC(90) not
      exceeding 1 microg ml(-1). Differences in resistance among Listeria spp. was
      displayed, as Listeria innocua strains were more resistant than other Listeria
      species. CONCLUSIONS: The study showed that Listeria monocytogenes strains from
      bison were susceptible to the antibiotics most commonly used to treat human
      listeriosis. However, the presence of antimicrobial resistance in L. innocua
      indicates the potential for transfer of resistance and a conjugative transposon
      to L. monocytogenes. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of our
      study will provide useful information for the development of public health policy
      in the use of antimicrobials in food animal production.

PMID- 17209821
TI  - Enumeration of thermotolerant Campylobacter spp. from poultry carcasses at the
      end of the slaughter-line.
AB  - AIM: To enumerate Campylobacter on poultry carcasses at the end of the slaughter
      line, and investigate the extent to which Campylobacter from a positive flock
      were transmitted to other flocks during slaughter. METHODS AND RESULTS: The
      presence (in caeca) and the level (from carcasses) of Campylobacter were
      determined. The isolates were fingerprinted by amplified fragment length
      polymorphism (AFLP). A total of three of 13 broiler flocks and three of four
      layer flocks harboured caecal Campylobacter. Carcasses from the caeca-positive
      broiler flocks were Campylobacter positive with numbers ranging from 2.6 x 10(4)
      to 2.6 x 10(6) CFU per carcass. Two caeca-negative broiler flocks, slaughtered
      directly after the positive broiler flocks, had the first carcasses contaminated
      with Campylobacter, with numbers below 2 x 10(4) CFU per carcass of the same AFLP
      haplotypes as the preceding flock. Campylobacter was detected on carcasses from
      only one of the caeca-positive layer flocks in numbers below 2 x 10(4) CFU per
      carcass. No Campylobacter was detected on carcasses from a flock succeeding the
      positive-layer flocks. CONCLUSION: Carcasses from Campylobacter-positive broiler
      flocks were heavily contaminated with Campylobacter, and transmitted low levels
      of Campylobacter to carcasses from negative flocks, slaughtered directly after.
      Campylobacter-positive layer flocks had low numbers of Campylobacter on the
      carcasses. SIGNIFICANCE AND IMPACT OF THE STUDY: The results indicate limited
      cross-contamination of Campylobacter between flocks at the slaughterhouse,
      reducing the advantage of logistic slaughter.

PMID- 17209822
TI  - Chitin-supplemented foliar application of chitinolytic Bacillus cereus reduces
      severity of Botrytis gray mold disease in chickpea under controlled conditions.
AB  - AIM: To identify and evaluate chitinolytic bacteria for control of Botrytis gray
      mold (BGM), a devastating disease in chickpea. METHODS AND RESULTS: Two
      antifungal bacterial isolates, chitinolytic Bacillus cereus CRS 7 and
      nonchitinolytic Pseudomonas fluorescens CRS 31, from the rhizosphere of chickpea,
      were applied as a prophylactic foliar spray and evaluated for control of BGM. In
      a controlled environment, the two isolates reduced the severity of BGM on the
      susceptible cv. JG 62 to 6.0 and 5.6, respectively, compared with 9.0 in the
      control, measured on a 1-9 rating scale. Supplementation of the foliar
      application of CRS 7 with 0.5% and 1.0% colloidal chitin reduced BGM severity to
      4.4 and 4.1 respectively, while chitin-supplemented application of CRS 31 was
      similar to CRS 31 applied alone. Partially purified 47-kDa chitinase from the
      cell-free culture filtrate of CRS 7 at 20 and 40 mug protein ml(-1) (enzyme
      activity 3.1 units ml(-1)) inhibited the germination and lysed the conidia of
      Botrytis cinerea, and as a prophylactic foliar spray reduced BGM severity to 5.4
      and 4.8, respectively. CONCLUSION: Chitin supplementation improved the biocontrol
      of the foliar disease BGM by chitinolytic bacterium. Disease control with
      partially purified chitinase of CRS 7 supported the major role of chitinolysis in
      improved control of BGM. SIGNIFICANCE AND IMPACT OF THE STUDY: Enhanced control
      of BGM by chitin-supplemented application of CRS 7 is of significant in view of
      the frequent inconsistency in biocontrol of foliar diseases. This study supports
      further attempts on chitinolysis-based biocontrol methods for foliar disease
      biocontrol.

PMID- 17209823
TI  - Evaluation of two viral extraction methods for the detection of human noroviruses
      in shellfish with conventional and real-time reverse transcriptase PCR.
AB  - AIMS: Comparison of two viral extraction methods in order to establish a
      sensitive and simple detection method for human noroviruses (NV) in bivalve
      shellfish. METHODS AND RESULTS: A direct RNA extraction method and an alkaline
      virus elution-concentration method were tested on artificially contaminated
      mussels. The latter used an alkaline buffer and polyethylene glycol (PEG) to
      isolate and concentrate the virus particles from shellfish. In both methods
      Trizol was used to release RNA. The final RNA extracts were amplified and
      detected with conventional and real-time reverse transcriptase PCR. The direct
      RNA extraction method was not able to detect low inoculation levels. However, the
      virus elution-concentration method was more sensitive. CONCLUSIONS: The alkaline
      elution-PEG concentration method followed by Trizol effectively removed
      inhibitory components and fulfilled the demands to be a useful tool for routine
      testing of shellfish for NV detection. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Because of the lack of standardized methods to detect NV in shellfish, many 'in
      house' extraction methods are used in practice. A comparison of these methods
      aims to determine a simple, rapid and sensitive method that could be a candidate
      method for screening suspected shellfish.

PMID- 17209824
TI  - Laboratory instrument contamination with dermatophytes - a risk for
      dermatophytosis.

PMID- 17209826
TI  - Antibacterial efficacy of calcium hydroxide intracanal dressing: a systematic
      review and meta-analysis.
AB  - AIM: To determine to what extent does calcium hydroxide intracanal medication
      eliminate bacteria from human root canals, compared with the same canals before
      medication, as measured by the number of positive cultures, in patients
      undergoing root canal treatment for apical periodontitis (teeth with an infected
      root canal system). METHODOLOGY: CENTRAL, MEDLINE and EMBASE databases were
      searched. Reference lists from identified articles were scanned. A forward search
      was undertaken on the authors of the identified articles. Papers that had cited
      these articles were also identified through the Science Citation Index to
      identify potentially relevant subsequent primary research. REVIEW METHODS: The
      included studies were pre-/post-test clinical trials comparing the number of
      positive bacterial cultures from treated canals. Data in those studies were
      independently extracted. Risk differences of included studies were combined using
      the generic inverse variance and random effect method. RESULTS: Eight studies
      were identified and included in the review, covering 257 cases. Sample size
      varied from 18 to 60 cases; six studies demonstrated a statistically significant
      difference between pre- and post-medicated canals, whilst two did not. There was
      considerable heterogeneity among studies. Pooled risk difference was -21%; 95%
      CI: -47% to 6%. The difference between pre- and post-medication was not
      statistically significant (P = 0.12). CONCLUSIONS: Calcium hydroxide has limited
      effectiveness in eliminating bacteria from human root canal when assessed by
      culture techniques.

PMID- 17209827
TI  - Dynamic recording of irrigating fluid distribution in root canals using thermal
      image analysis.
AB  - AIM: To investigate the influence of the size and the depth of insertion of
      irrigating needles, and the diameter of the master apical file on flow
      distribution during fluid irrigation in root canals. METHODOLOGY: Stepback canal
      instrumentation was employed on seven extracted human single canal teeth. The
      size of the master apical files ranged from sizes 25, 30, 35, 40, 45, 50 to size
      80 within the seven teeth, respectively. A thermal imaging system (ThermaCAM;
      National Instruments Co., Austin, TX, USA) was used to record the dynamic fluid
      distribution following root canal preparation. The dynamic fluid distribution was
      analysed during irrigation by insertion of different irrigating needle tips (23,
      25 and 27 gauge) at various depths (3, 6 and 9 mm) from the root apex. The whole
      process of irrigation was recorded by a video camera and analysed by two
      observers separately. The success of the irrigation process was defined when the
      irrigant was able to flow into to the apical region immediately after injection.
      RESULTS: The aqueous irrigant was flushed into the apical region when a size 27
      gauge irrigating needle was placed into a size 30 canal at a point 3 mm from the
      apical stop. When the same needle tip was placed 6 mm from the root canal apex,
      successful irrigation was achieved only in the canals prepared to size 50 or
      larger. When a size 25 gauge irrigating needle was placed 3 mm from the working
      length, the canal size had to be no <45 to allow for successful irrigation. When
      a size 23 gauge needle was placed at the same position, the canal needed to be
      prepared to size 50 to allow thorough irrigation of the apex. At 9 mm from the
      apical stop, none of the irrigating needles could achieve successful irrigation
      of any canal size. CONCLUSION: The flow distribution of root canal irrigation can
      be affected adversely by large diameter irrigating needles, by greater distances
      between the needle tip and the apical stop, and by narrow root canals.

PMID- 17209828
TI  - Evaluation of the surface free energy on root canal dentine walls treated with
      chelating agents and NaOCl.
AB  - AIM: To evaluate ex vivo the effects of combined and single use of EDTA, RC-Prep
      and NaOCl on the surface free energy of canal wall dentine using the captive
      bubble technique. METHODOLOGY: Eighteen extracted human pre-molar teeth were
      sectioned at the crown and the apical third, the remaining mid-root portion were
      bisected longitudinally. Thereafter, the root halves were embedded in resin
      blocks that exposed the dentine surface of the canal wall. The specimens were
      randomly assigned to six experimental groups (n = 6) after polishing. The root
      dentine surfaces of the first two groups were treated with 17% EDTA or RC-Prep
      followed by 2.5% NaOCl irrigation. Groups 3, 4 and 5 were treated with either 17%
      EDTA, RC-Prep or 2.5% NaOCl alone. Control specimens were irrigated with saline
      solution. The surface free energies of experimental groups were calculated by
      measuring air and octane contact angles on the canal wall dentine. Statistical
      analysis was performed using the Mann-Whitney U and Bonferroni post-tests at P =
      0.05. RESULTS: Compared with the control group; combined and single use of EDTA,
      RC-Prep and NaOCl irrigation significantly decreased the surface free energy of
      canal wall dentine surfaces (P < 0.05). Among all groups tested, the use of NaOCl
      as a final flush following RC-Prep treatment yielded increased wettability.
      Nevertheless, this value remained lower than that of the control group.
      CONCLUSION: Use of chelating agents alone or in combination with NaOCl decreased
      the wettability of root canal wall dentine.

PMID- 17209829
TI  - Degradation of trans-polyisoprene over time following the analysis of root
      fillings removed during conventional retreatment.
AB  - AIM: To evaluate in vivo degradation of root filling materials over time.
      METHODOLOGY: Thirty-six root filled teeth with or without periapical lesions were
      selected. Teeth with poor coronal restoration were not included. The teeth had
      been root filled 3-30 years previous and were scheduled for conventional
      retreatment. The association of root canal treatment, age, periapical lesion and
      root filling degradation was investigated. The filling material was removed from
      the root canal using files and no solvent. Trans-1,4-polyisoprene was isolated
      through solubilization of root filling remnants in chloroform followed by
      filtration and centrifugation. Gel permeation chromatography (GPC) and infrared
      spectroscopy (FT-IR) were utilized to study the occurrence and degree of
      degradation. The GPC and FT-IR data were collected for each sample and analysed
      statistically using the Kruskal-Wallis test. RESULTS: Degradation of trans-1,4
      polyisoprene was a slow process. The process was identified as an oxidation
      reaction through the production of carboxyl and hydroxyl groups. Compared with
      the control group, significant molar mass decrease was noted after 15 years (P =
      0.0146) in teeth with no periapical lesions. However, in teeth associated with
      periapical lesions the number of years for significant degradation was reduced to
      5 (P = 0.0009). CONCLUSION: Polyisoprene degrades inside root canals as an
      oxidative process. The presence of periapical lesions was associated with a more
      rapid onset of degradation.

PMID- 17209830
TI  - Resistance to fracture of roots filled with three different techniques.
AB  - AIM: To compare the fracture resistance of roots filled with different materials.
      METHODOLOGY: Thirty-four freshly extracted human maxillary central incisor teeth
      with similar dimension were selected. Crowns were sectioned at the cemento-enamel
      junction, and the length of the roots were adjusted to 13 mm. Following the
      preparation of the root canals and final irrigation with EDTA and saline, the 10
      root canals in group 1 were filled with Resilon cones and Epiphany sealer, the 10
      root canals in group 2 were filled with gutta-percha and AH 26 and the 10 root
      canals in group 3 were filled with gutta-percha and MCS Canal Sealer. All
      materials were used with a cold lateral condensation technique. Four root canals
      remained unfilled and were used as a control group. Tests for fracture strength
      were performed using a universal testing machine and a round tip that had a
      diameter of 4 mm. The force was applied vertically with a constant speed of 1 mm
      min(-1). For each root, the force at the time of fracture was recorded in
      Newtons. Results were evaluated statistically with ANOVA and Tukey Honestly
      Significant Difference (HSD) tests. RESULTS: The mean force of fracture values
      was 1043 N, 967 N, 859 N and 517.5 N for groups 3, 1 and 2 and the control group,
      respectively. There was a significant difference (P < 0.01) between the
      experimental groups and the control group. No significant differences were found
      between the three experimental groups. CONCLUSIONS: All the materials used in the
      present study reinforced the prepared root canals.

PMID- 17209831
TI  - The corrosion of nickel-titanium rotary endodontic instruments in sodium
      hypochlorite.
AB  - AIM: To evaluate the corrosion resistance of nickel-titanium (NiTi) endodontic
      rotary instruments immersed in 5.25% sodium hypochlorite (NaOCl) solution.
      METHODOLOGY: The corrosion performance of NiTi instruments (S1 25 mm, ProTaper
      Dentsplay Maillefer, Ballaigues, Switzerland) was evaluated using commercial
      5.25% NaOCl solution (pH = 12.3), and the same solution partially neutralized
      adding H2SO4 to reach pH = 10.1. Electrochemical measurements were carried out
      using a potentiostat equipped with a five-channel zero resistance ammeter (ZRA)
      for galvanic current measurements. The instruments were sectioned into three
      parts (cutting part, noncutting part and shank) and degreased with acetone and
      rinsing with demineralized water prior to being immersed in NaOCl solution for
      testing. Each set of the three parts constituted one 'virtual' instrument through
      the ZRA, giving access to the galvanic currents that circulate between the three
      parts. Nine instruments were employed to check the reproducibility of the
      electrochemical measurements. RESULTS: The corrosion potential (E(corr)) of the
      NiTi alloy reached the passive domain in approximately 20 s of immersion in the
      solution having a pH 10.1. After this initial period the potential remained
      steady, indicating that stable passivation was achieved. However, at pH 12.3 no
      stationary state was achieved even after 6000 s of immersion time. Thus, the
      alloy was not stable in this medium from a corrosion point of view. CONCLUSIONS:
      The corrosion resistance of NiTi alloy was enhanced by lowering the pH of NaOCl
      solution to 10.1, which allows the system to reach the stability domain of the
      passivating species TiO2 and NiO2.

PMID- 17209832
TI  - Influence of a brushing working motion on the fatigue life of NiTi rotary
      instruments.
AB  - AIM: To evaluate the cyclic fatigue resistance of Mtwo NiTi rotary instruments
      when used with a brushing or no-brushing action in oval root canals. METHODOLOGY:
      Cyclic fatigue testing of instruments was performed in tapered artificial canals
      with a 5 mm radius of curvature and an angle of curvature of 60 degrees. Twenty
      Mtwo instruments for each size were selected and divided into two groups: group A
      = 10 instruments used with a no-brushing motion (control group); group B = 10
      instruments used with a brushing-milling action. Each Mtwo instrument was used
      for cleaning and shaping 10 oval root canals. In all 80 instruments were rotated
      until fracture occurred and the number of cycles to failure (NCF) recorded. Data
      were analysed by one-way ANOVA, Tukey HSD test and independent sample t-test to
      determine any statistical difference; the significance was determined at the 95%
      confidence level. RESULTS: No statistically significant reduction of NCF between
      instruments used with a no-brushing motion (group A) and instruments used with a
      brushing motion (group B) were apparent except for size 25, 0.06 taper. Mtwo size
      10, 0.04 taper, size 15, 0.05 taper, size 20, 0.06 taper, size 25, 0.06 taper
      instruments had a decrease in life span of 1%, 0.5%, 8% and 19%, respectively.
      CONCLUSIONS: Fatigue life of instruments of larger size could be reduced by using
      them with a lateral brushing or pressing movement. However, each file was
      successfully operated without intracanal failure, demonstrating that Mtwo rotary
      instruments can be used safely in a brushing action in simulated clinical
      conditions up to 10 times in oval canals.

PMID- 17209833
TI  - The evaluation of removal of calcium hydroxide paste from an artificial
      standardized groove in the apical root canal using different irrigation
      methodologies.
AB  - AIM: To evaluate the capacity to remove a calcium hydroxide (Ca(OH)2) paste from
      the root canal and to evaluate the efficacy of Ca(OH)2 removal during passive
      ultrasonic irrigation using either sodium hypochlorite (NaOCl) or water as an
      irrigant. METHODOLOGY: Sixteen mandibular premolars were used. Each root was
      prepared to the apical foramen using GT instruments of size 30, 0.06 taper. Each
      root was split longitudinally. In one half of the root, a groove was cut in the
      canal wall 2-6 mm from the apex which was then filled with a Ca(OH)2 paste.
      Subsequently the roots were reassembled. In group 1 (n = 16), the teeth were
      ultrasonically irrigated using 50 mL 2.0% NaOCl as the irrigant. Group 2 (n = 16)
      was treated in the same manner as group 1, but using 50 mL water in place of the
      NaOCl. In group 3 (n = 16), the teeth were irrigated by syringe injection of 50
      mL 2.0% NaOCl. The quantity of remaining Ca(OH)2 in the groove was scored and the
      data analysed with Kruskal-Wallis and Mann-Whitney tests. RESULTS: The difference
      in remaining Ca(OH)2 between all groups was statistically significant (P <
      0.001). Group 1 had significantly lower scores than group 2 (P < 0.001) and group
      3 (P = 0.002), but there was no significant difference between groups 2 and 3 (P
      = 0.765). CONCLUSIONS: Passive ultrasonic irrigation with 2% NaOCl was more
      effective in removing Ca(OH)2 paste from artificial root canal grooves than
      syringe delivery of 2% NaOCl or water as irrigant.

PMID- 17209834
TI  - Effects of a new antibacterial adhesive on the repair capacity of the pulp
      dentine complex in infected teeth.
AB  - AIM: To evaluate the effects of a self-etching/priming adhesive system,
      containing the antibacterial monomer 12-methacryloyloxy-dodecylpyridinium bromide
      (MDPB), on the repair capacity of the pulp-dentine complex in infected cavities
      in dog's teeth. METHODOLOGY: Class V cavities with a residual dentine thickness
      ranging from 0.3-0.8 mm were prepared on the buccal surface of permanent teeth in
      four dogs. Pulpal exposures were performed in half of the cavities. Millipore
      filters that had been incubated for 3 h in a 10(5) milky suspension of a
      streptococci were placed in the cavities, which were then filled temporarily.
      After 24 h, the filters were removed and both the exposed and non-exposed
      cavities were washed with sterile saline and assigned to four groups which were
      treated with either the experimental antibacterial adhesive system, or Clearfil
      SE bond, Dycal and Teflon discs. Stereotype connective tissue reactions
      (inflammatory cell response and/or tissue necrosis) and pulp-specific reparative
      tissue responses (reduction of odontoblasts and tertiary dentine formation) were
      assessed at post-operative periods of 4 and 8 weeks. RESULTS: Neither severe
      inflammation nor tissue necrosis was observed, either in the dentinal cavities or
      pulpal exposures treated with the self-etch adhesive containing MDPB. Rates of
      tertiary dentine formation in infected dentinal cavities treated with this system
      were comparable with those observed after dentine treatment with the Ca(OH)2
      based material. Dentinal bridging was not seen in pulpal exposures treated with
      the experimental adhesive. CONCLUSIONS: The new antibacterial adhesive system
      maintained pulp vitality and primary odontoblastic function in infected
      nonexposed and exposed cavities but interfered with reparative dentine formation
      in infected pulpal exposures.

PMID- 17209835
TI  - The penetration of RealSeal primer and Tubliseal into root canal dentinal
      tubules: a confocal microscopic study.
AB  - AIM: To compare penetration depth into dentinal tubules of RealSeal with that of
      a well-established endodontic sealer (Tubliseal) by means of confocal microscopy.
      METHODOLOGY: Twenty sound extracted, single-rooted premolars were selected.
      Following completion of root canal instrumentation, the teeth were divided into
      two groups using a stratified sampling method, ranking teeth according to size.
      In group 1, 10 teeth were filled with Gutta-percha and Tubliseal using cold
      lateral condensation. In group 2, 10 teeth were filled with RealSeal. Both
      sealers were labelled with Rhodamine B dye. The teeth were sectioned parallel to
      their long axis resulting in 20 specimens per group. Confocal microscopy was used
      to assess the penetration depths of the sealers at three sites for each specimen
      (coronal, middle and apical). Data were analysed statistically using Stata
      Release 9.1. RESULTS: The penetration depth of RealSeal in each one of the thirds
      of the root canal was found to be higher than that of Tubliseal (P < 0.05). The
      penetration depths of the two sealers was found to be significantly different (P
      = 0.001). The mean penetration value for the RealSeal group was 908.8 microm
      whereas the mean value for the Tubliseal group was 139.5 microm. CONCLUSIONS: The
      penetration depth of RealSeal into the root dentinal tubules is significantly
      greater than that of Tubliseal.

PMID- 17209836
TI  - Intraosseous schwannoma mimicking a periapical lesion on the adjacent tooth: case
      report.
AB  - AIM: To present an additional case of intraosseous schwannoma involving the
      apical area in the mandibular alveolar bone mimicking an inflammatory periapical
      lesion. SUMMARY: This article describes a case of schwannoma periapically located
      mimicking an inflammatory periapical lesion in the mandible of a 34-year-old
      female. Diagnostic and therapeutic problems can occur when this lesion is
      misinterpreted as being endodontic in origin. The diagnosis, radiograph,
      immunohistochemical aspects and treatment are also discussed. KEY LEARNING
      POINTS: Intraosseous schwannoma is a rare unilocular radiolucency that when
      located periapically could be misdiagnosed as an endodontic lesion and result in
      unnecessary root canal treatment. The vitality of the pulp is an important test
      to exclude lesions of inflammatory origin. Histological examination is important
      to establish the diagnosis of lesions in the periradicular region.

PMID- 17209848
TI  - Helicobacter pylori-induced atrophic gastritis progressing to gastric cancer
      exhibits sonic hedgehog loss and aberrant CDX2 expression.
AB  - BACKGROUND: The loss of sonic hedgehog is an early change that occurs in the
      mucosa prior to neoplastic transformation and correlates with the type of
      intestinal metaplasia. Aberrant expression of CDX has also been shown to
      correlate with the development of intestinal metaplasia. AIM: To examine CDX2
      expression in the non-cancerous mucosa of patients with gastric cancer and
      compared it to CDX2 expression in controls with intestinal metaplasia. METHODS:
      Sixty patients who had undergone endoscopic mucosal resection for early gastric
      cancer and 60 gender- and age-matched controls were studied. Two specimens each
      were obtained from the greater and lesser curves of the corpus and from the
      greater curve of the antrum. Expression of CDX2 and sonic hedgehog were evaluated
      by immunostaining. RESULTS: Gastric cancer was associated with a higher frequency
      of incomplete intestinal metaplasia (OR = 8.3; 95%CI, 3.7-18.9, P < 0.001). CDX2
      negatively correlated with sonic hedgehog expression, however, multivariate
      analysis revealed that CDX2 correlated with the intestinal metaplasia scores.
      Sonic hedgehog indices were lower and CDX2 staining in the corpus lesser curve
      was higher in the cancer group than in the controls. Sonic hedgehog indices in
      the corpus decreased and CDX2 indices in both areas increased in patients in the
      ascending order of those without intestinal metaplasia, those with complete
      intestinal metaplasia and those with incomplete intestinal metaplasia (P <
      0.001). CONCLUSIONS: Loss of sonic hedgehog expression and aberrant expression of
      CDX2 correlates with the type of intestinal metaplasia and may play a role in
      carcinogenesis.

PMID- 17209861
TI  - Review article: duodenal bicarbonate - mucosal protection, luminal chemosensing
      and acid-base balance.
AB  - The duodenum serves as a buffer zone between the stomach and the jejunum. Over a
      length of only 25 cm, large volumes of strong acid secreted by the stomach must
      be converted to the neutral-alkaline chyme of the hindgut lumen, generating large
      volumes of CO(2). The duodenal mucosa consists of epithelial cells connected by
      low-resistance tight junctions, forming a leaky epithelial barrier. Despite this
      permeability, the epithelial cells, under intense stress from luminal mineral
      acid and highly elevated Pco(2), maintain normal functioning. Bicarbonate ion
      uniquely protects the duodenal epithelial cells from acid-related injury. The
      specific protective mechanisms likely involve luminal bicarbonate secretion,
      intracellular pH buffering and interstitial buffering. Furthermore, the duodenum
      plays an active role in foregut acid-base homeostasis, absorbing large amounts of
      H(+) and CO(2). We have studied mucosal protection and acid-base balance using
      live-animal fluorescence ratio microimaging and by performing H(+) and CO(2)
      balance studies on duodenal perfusates. On the basis of these data, we have
      formulated novel hypotheses with regard to mucosal protection.

PMID- 17209882
TI  - Re: Penile duplex pharmaco-ultrasonography of cavernous arteries in men with
      erectile dysfunction and generalized atherosclerosis.

PMID- 17209884
TI  - Leptin levels in infertile male patients are correlated with inhibin B,
      testosterone and SHBG but not with sperm characteristics.
AB  - In the present study, differences in leptin levels between different groups of
      male patients presenting with infertility problems and possible correlations
      between leptin levels and clinical, spermiological, histological and hormonal
      characteristics were examined. Two hundred and ten male partners from infertile
      couples were included in the study. Based on clinical examination, spermiogram
      and testicular histology results, patients were divided into four groups: 42 men
      with non-obstructive azoospermia, 15 men with obstructive azoospermia, 68 men
      with oligoasthenoteratozoospermia and 85 men with normozoospermia. Serum levels
      of follicle-stimulating hormone (FSH), luteinizing hormone (LH), inhibin B,
      testosterone, sex hormone binding globulin (SHBG) and leptin were measured. After
      adjustment for body mass index, there was a negative correlation between serum
      levels of leptin and inhibin B, total testosterone and SHBG (r = -0.189, p =
      0.009, r = -0.250, p = 0.001 and r =-0.221, p = 0.003 respectively) but there was
      no correlation between leptin and classical sperm characteristics. Our results
      therefore demonstrate a link between leptin and testicular function,
      independently of FSH and LH, possibly involving testosterone and SHBG through a
      regulation of Leydig cell function.

PMID- 17209885
TI  - Use of cellular and cordless telephones and risk of testicular cancer.
AB  - A case-control study on testicular cancer included use of cellular and cordless
      telephones. The results were based on answers from 542 (92%) cases with seminoma,
      346 (89%) with non-seminoma, and 870 (89%) controls. Regarding seminoma the use
      of analog cellular phones gave odds ratio (OR) = 1.2, 95% confidence interval
      (CI) = 0.9-1.6, digital phones OR = 1.3, CI = 0.9-1.8, and cordless phones OR =
      1.1, CI = 0.8-1.5. The corresponding results for non-seminoma were OR = 0.7, CI =
      0.5-1.1, OR = 0.9, CI = 0.6-1.4, and OR = 1.0, CI = 0.7-1.4, respectively. There
      was no dose-response effect and OR did not increase with latency time. No
      association was found with place of keeping the mobile phone during standby, such
      as trousers pocket. Cryptorchidism was associated both with seminoma (OR = 4.2,
      CI = 2.7-6.5) and non-seminoma (OR = 3.3, CI = 2.0-5.6), but no interaction was
      found with the use of cellular or cordless telephones.

PMID- 17209886
TI  - A resident's reflections on becoming an agent of curricular change.

PMID- 17209887
TI  - Medical students' learning of anatomy: memorisation, understanding and
      visualisation.
AB  - INTRODUCTION: There is much subjective discussion, but few empirical data that
      explore how students approach the learning of anatomy. AIMS: Students'
      perceptions of successful approaches to learning anatomy were correlated with
      their own approaches to learning, quality of learning and grades. METHODS: First
      year medical students (n = 97) studying anatomy at an Australian university
      completed an online survey including a version of the Study Process Questionnaire
      (SPQ) that measures approaches to learning. The quality of students' written
      assessment was rated using the Structure of Observed Learning Outcomes (SOLO)
      taxonomy. Final examination data were used for correlation with approaches and
      quality of learning. RESULTS: Students perceived successful learning of anatomy
      as hard work, involving various combinations of memorisation, understanding and
      visualisation. Students' surface approach (SA) scores (mean 30 +/- 3.4) and deep
      approach (DA) scores (mean 31 +/- 4.2) reflected the use of both memorisation and
      understanding as key learning strategies in anatomy. There were significant
      correlations between SOLO ratings and DA scores (r = 0.24, P < 0.01), between SA
      scores and final grades (r = - 0.30, P < 0.01) and between SOLO ratings and final
      grades (r = 0.61, P < 0.01) in the subject. CONCLUSIONS: Approaches to learning
      correlate positively with the quality of learning. Successful learning of anatomy
      requires a balance between memorisation with understanding and visualisation.
      Interrelationships between these three strategies for learning anatomy in
      medicine and other disciplines require further investigation.

PMID- 17209888
TI  - Anatomical dissection as a teaching method in medical school: a review of the
      evidence.
AB  - CONTEXT: Discussions about dissection as a teaching method in gross anatomy are
      characterised by a lack of objective evidence. METHODS: A search for such
      evidence in the literature produced 14 relevant papers. These were reviewed for
      objective data on the effect of cadaver dissection on cognitive learning
      outcomes. RESULTS: All reviewed studies compared groups of students exposed to
      different teaching approaches, including active dissection, learning on prosected
      material, or a combination with computerised teaching aids. Study and course
      designs varied substantially and student groups compared were not always
      homogeneous. In all studies, compared learning experiences differed in more than
      1 variable, and assessment of anatomical knowledge was not standardised.
      DISCUSSION: It is difficult to interpret and generalise from the results of the
      reviewed studies. Considering the bias that must be assumed for teachers who
      develop new course designs and compare these with traditional ones, the review
      shows a slight advantage for traditional dissection over prosection. CONCLUSIONS:
      More sophisticated research designs may be necessary to solve the general problem
      of the small measurable impact of educational interventions and to come to
      scientifically sound conclusions about the best way to teach gross anatomy. Such
      research will have to include sufficient sample sizes, the use of validated
      assessment instruments, and a discussion of the educational significance of
      measured differences. More educational research in anatomy is necessary to
      counterbalance emotional arguments about dissection with scientific evidence.
      Anatomical knowledge is too important to future doctors to leave its teaching to
      the educational fashion of the day.

PMID- 17209889
TI  - Spaced education improves the retention of clinical knowledge by medical
      students: a randomised controlled trial.
AB  - PURPOSE: Medical knowledge learned by trainees is often quickly forgotten. How
      can the educational process be tailored to shift learning into longer-term
      memory? We investigated whether 'spaced education', consisting of weekly e-mailed
      case scenarios and clinical questions, could improve the retention of students'
      learning. METHODS: During the 2004-5 surgery clerkships, 3rd-year students
      completed a mandatory 1-week clinical rotation in urology and validated web-based
      teaching programme on 4 core urology topics. Spaced educational e-mails were
      constructed on all 4 topics based on a validated urology curriculum. Each
      consisted of a short clinically relevant question or clinical case scenario in
      multiple-choice question format, followed by the answer, teaching point summary
      and explanations of the answers. Students were randomised to receive weekly e
      mailed case scenarios in only 2 of the 4 urology topics upon completion of their
      urology rotation. Students completed a validated 28-item test (Cronbach's alpha =
      0.76) on all 4 topics prior to and after the rotation and at the end of the
      academic year. RESULTS: A total of 95 of 133 students (71%) completed the end-of
      year test. There were no significant differences in baseline characteristics
      between randomised cohorts. Spaced education significantly improved composite end
      of-year test scores (P < 0.001, paired t-test). The impact of the spaced
      educational e-mails was largest for those students who completed their urology
      education 6-8 and 9-11 months previously (Cohen's effect sizes of 1.01 and 0.73,
      respectively). CONCLUSION: Spaced education consisting of clinical scenarios and
      questions distributed weekly via e-mail can significantly improve students'
      retention of medical knowledge.

PMID- 17209890
TI  - Conditional reliability of admissions interview ratings: extreme ratings are the
      most informative.
AB  - CONTEXT: Admissions interviews are unreliable and have poor predictive validity,
      yet are the sole measures of non-cognitive skills used by most medical school
      admissions departments. The low reliability may be due in part to variation in
      conditional reliability across the rating scale. OBJECTIVES: To describe an
      empirically derived estimate of conditional reliability and use it to improve the
      predictive validity of interview ratings. METHODS: A set of medical school
      interview ratings was compared to a Monte Carlo simulated set to estimate
      conditional reliability controlling for range restriction, response scale bias
      and other artefacts. This estimate was used as a weighting function to improve
      the predictive validity of a second set of interview ratings for predicting non
      cognitive measures (USMLE Step II residuals from Step I scores). RESULTS:
      Compared with the simulated set, both observed sets showed more reliability at
      low and high rating levels than at moderate levels. Raw interview scores did not
      predict USMLE Step II scores after controlling for Step I performance (additional
      r2 = 0.001, not significant). Weighting interview ratings by estimated
      conditional reliability improved predictive validity (additional r2 = 0.121, P <
      0.01). CONCLUSIONS: Conditional reliability is important for understanding the
      psychometric properties of subjective rating scales. Weighting these measures
      during the admissions process would improve admissions decisions.

PMID- 17209891
TI  - Women in medicine--is there a problem? A literature review of the changing gender
      composition, structures and occupational cultures in medicine.
AB  - BACKGROUND: Internationally, there are increasing numbers of women entering
      medicine. Although all countries have different health care systems and social
      contexts, all still show horizontal (women concentrated in certain areas of work)
      and vertical (women under represented at higher levels of the professions)
      segregation. There is much discussion and competing explanations about the
      implications of the increasing numbers of women in the medical profession. AIMS:
      The purpose of this review was to explore the evidence, issues and explanations
      to understand the effects of the changing composition of the medical profession.
      CONCLUSIONS: This review identified evidence that delineates some of the effects
      of gender on the culture, practice and organisation of medicine. There are
      problems with some of the research methodologies and we identify areas for
      further research. To understand the effects of the changing gender composition of
      medicine it will be necessary to use more sophisticated research designs to
      explore the structural, economic, historical and social contexts that interact to
      produce medical culture. This will provide a basis for exploring the impact and
      implications of these changes and has immediate relevance for workforce planning
      and understanding both the changing nature of health professions' education and
      health care delivery.

PMID- 17209892
TI  - Factors affecting future choice of specialty among first-year medical students of
      the University of the West Indies, Trinidad.
AB  - BACKGROUND: This study was conducted to determine factors that influence career
      choice among 1st-year medical students. DESIGN AND METHODS: A cross-sectional
      survey of 170 1st-year medical students from the University of the West Indies,
      St Augustine Campus was undertaken with a questionnaire designed to assess their
      perceptions of careers in various specialties. Likert scales were used to
      quantify the reasons for their preferences. RESULTS: The response rate was
      136/170 (80%). The age of respondents ranged from 16 to 36 years, mean 20.45, SD
      2.88. Of the generic factors students considered important in their choice of a
      specialty, students ranked the ability to help patients the highest (rating of
      1.44), along with the diagnosis and treatment of disease second (rating of 1.49);
      38 (27.9%) cited medicine, 26 (19.1%) surgery, 13 (9.6%) paediatrics, 10 (7.4%)
      family practice and 4 (2.9%) psychiatry as their chosen career. Students begin
      their medical training with the view that a career in psychiatry is less
      attractive than other specialties surveyed. The average attractiveness was
      estimated as surgery 1.64, medicine, 1.81, paediatrics 1.95 and psychiatry 2.57.
      The differences between the averages were highly significant (F = 57.6, P <
      0.001). CONCLUSION: The findings suggest that although 1st-year medical students
      rank the diagnosis and treatment of disease and the ability to help patients as
      the greatest influence in choosing a specialty, internal medicine was the most
      popular chosen career, while the surgical specialties were identified as the most
      attractive. Medical students have serious reservations about psychiatry as a
      career choice.

PMID- 17209893
TI  - Effectiveness of medical school admissions criteria in predicting residency
      ranking four years later.
AB  - BACKGROUND: Medical schools across Canada expend great effort in selecting
      students from a large pool of qualified applicants. Non-cognitive assessments are
      conducted by most schools in an effort to ensure that medical students have the
      personal characteristics of importance in the practice of Medicine. We reviewed
      the ability of University of Toronto academic and non-academic admission
      assessments to predict ranking by Internal Medicine and Family Medicine residency
      programmes. METHODS: The study sample consisted of students who had entered the
      University of Toronto between 1994 and 1998 inclusive, and had then applied
      through the Canadian resident matching programme to positions in Family or
      Internal Medicine at the University of Toronto in their graduating year. The
      value of admissions variables in predicting medical school performance and
      residency ranking was assessed. RESULTS: Ranking in Internal Medicine correlated
      significantly with undergraduate grade point average (GPA) and the admissions non
      cognitive assessment. It also correlated with 2-year objective structured
      clinical examination (OSCE) score, clerkship grade in Internal Medicine, and
      final grade in medical school. Ranking in Family Medicine correlated with the
      admissions interview score. It also correlated with 2nd-year OSCE score,
      clerkship grade in Family Medicine, clerkship ward evaluation in Internal
      Medicine and final grade in medical school. DISCUSSION: The results of this study
      suggest that cognitive as well as non-cognitive factors evaluated during medical
      school admission are important in predicting future success in Medicine. The non
      cognitive assessment provides additional value to standard academic criteria in
      predicting ranking by 2 residency programmes, and justifies its use as part of
      the admissions process.

PMID- 17209894
TI  - Risk factors for poor performance on the undergraduate medical course: cohort
      study at Nottingham University.
AB  - OBJECTIVE: To determine the risk factors for poor performance at different stages
      of the undergraduate medical course. DESIGN: Longitudinal retrospective cohort
      study of progress on a 5-year undergraduate medical course. SETTING: The
      University of Nottingham medical school. PARTICIPANTS: All students (594) who
      joined the course in 3 consecutive years were followed throughout their course
      until graduation, even if this was delayed. RESULTS: Risk factors for poor
      performance varied at different stages on the course. Students with lower A
      levels were at increased risk throughout, but primarily in the pre-clinical
      course. Non-white ethnicity was also a risk factor, independent of domicile, but
      this was associated more strongly with lower marks on the clinical course. Males
      and those who received a later offer of a place were at some risk throughout the
      course. Overall attrition from the course was 5%, and 34/594 students (6%) spent
      more than the normal 5 years on the course. CONCLUSION: School performance
      remains an important indicator of ability to cope with the pre-clinical course.
      Further research is required to understand why ethnic minority students may be
      more at risk at all stages, but particularly in the clinical course, and to
      increase their use of existing support services if necessary.

PMID- 17209895
TI  - Behaviour of medical students in seeking mental and physical health care:
      exploration and comparison with psychology students.
AB  - CONTEXT: Doctors are often reluctant to seek health care through the usual
      channels and tend to self-diagnose and prescribe. Medical students learn
      attitudes and values from clinician role models and may also adopt behaviour
      patterns that lead them to seek help for physical and mental health problems from
      informal sources. OBJECTIVES: This study aimed to explore the behaviour of
      students in seeking health care for physical and mental health problems,
      comparing medical with psychology students, and to understand what barriers to
      conventional routes of seeking health care may affect this. METHODS: We
      administered a questionnaire asking for demographic details and responses to 2
      vignettes in which a student from the respondent's discipline was experiencing
      firstly symptoms of a mental health problem and secondly symptoms of a physical
      health problem. Data were analysed with spss and univariate anovas to examine
      differences between respondents. RESULTS: A total of 172 students at the
      psychology and medical schools at James Cook University in Australia
      participated. We identified a number of barriers affecting student behaviour in
      seeking help, which included worries about knowing the doctor they could consult
      at the university health centre or having future dealings with him or her, and
      cost of treatment. There were differences between the 2 groups of students.
      DISCUSSION: There are several barriers for both psychology and medical students
      to accessing appropriate professional mental health care. Medical students also
      experience barriers to attaining appropriate physical health care when needed.
      Psychology and medical students were more likely to seek advice informally from
      friends and/or family with regard to mental health care.

PMID- 17209896
TI  - Experience-based learning: a model linking the processes and outcomes of medical
      students' workplace learning.
AB  - OBJECTIVE: To develop a model linking the processes and outcomes of workplace
      learning. METHODS: We synthesised a model from grounded theory analysis of group
      discussions before and after experimental strengthening of medical students'
      workplace learning. The research was conducted within a problem-based clinical
      curriculum with little early workplace experience, involving 24 junior and 12
      senior medical students. RESULTS: To reach their ultimate goal of helping
      patients, medical students must develop 2 qualities. One is practical competence;
      the other is a state of mind that includes confidence, motivation and a sense of
      professional identity. These 2 qualities reinforce one another. The core process
      of clinical workplace learning involves 'participation in practice', which
      evolves along a spectrum from passive observation to performance. Practitioners
      help students participate by being both supportive and challenging. The
      presentation of clear learning objectives and continuous periods of attachment
      that are as personal to the student(s) and practitioner(s) as possible promote
      workplace learning. CONCLUSIONS: The core condition for clinical workplace
      learning is 'supported participation', the various outcomes of which are mutually
      reinforcing and also reinforce students' ability to participate in further
      practice. This synthesis has 2 important implications for contemporary medical
      education: any reduction in medical students' participation in clinical practice
      that results from the patient safety agenda and expanded numbers of medical
      students is likely to have an adverse effect on learning, and the construct of
      'self-directed learning', which our respondents too often found synonymous with
      'lack of support', should be applied with very great caution to medical students'
      learning in clinical workplaces.

PMID- 17209897
TI  - Psychometric properties of an instrument to measure the clinical learning
      environment.
AB  - OBJECTIVES: The clinical learning environment is an influential factor in work
      based learning. Evaluation of this environment gives insight into the educational
      functioning of clinical departments. The Postgraduate Hospital Educational
      Environment Measure (PHEEM) is an evaluation tool consisting of a validated
      questionnaire with 3 subscales. In this paper we further investigate the
      psychometric properties of the PHEEM. We set out to validate the 3 subscales and
      test the reliability of the PHEEM for both clerks (clinical medical students) and
      registrars (specialists in training). METHODS: Clerks and registrars from
      different hospitals and specialties filled out the PHEEM. To investigate the
      construct validity of the 3 subscales, we used an exploratory factor analysis
      followed by varimax rotation, and a cluster analysis known as Mokken scale
      analysis. We estimated the reliability of the questionnaire by means of variance
      components according to generalisability theory. RESULTS: A total of 256 clerks
      and 339 registrars filled out the questionnaire. The exploratory factor analysis
      plus varimax rotation suggested a 1-dimensional scale. The Mokken scale analysis
      confirmed this result. The reliability analysis showed a reliable outcome for 1
      department with 14 clerks or 11 registrars. For multiple departments 3
      respondents combined with 10 departments provide a reliable outcome for both
      groups. DISCUSSION: The PHEEM is a questionnaire measuring 1 dimension instead of
      the hypothesised 3 dimensions. The sample size required to achieve a reliable
      outcome is feasible. The instrument can be used to evaluate both single and
      multiple departments for both clerks and registrars.

PMID- 17209898
TI  - Teaching undergraduate psychiatry in primary care: the impact on student learning
      and attitudes.
AB  - OBJECTIVE: To explore the impact of undergraduate psychiatry placements in
      primary care settings on students' learning and attitudes to mental illness.
      DESIGN: Questionnaire survey and qualitative in-depth interviews. SETTING: A
      primary care-based psychiatry undergraduate teaching programme at Royal Free and
      University College Medical School, London. PARTICIPANTS: A total of 145/183
      (79.2%) students attending the primary care-based programme over 2 academic years
      completed a questionnaire survey. In-depth interviews were conducted with 14
      students, 12 general practitioner (GP) tutors and 20 patients participating in
      the course. RESULTS: In the questionnaire survey, 121/144 (84.0%) students valued
      the primary care-based teaching highly. In total, 87/139 (62.6%) students felt
      their attitudes to mental illness had changed as a result of the course. In-depth
      interviews demonstrated 4 key benefits of the teaching programme: increasing
      breadth of experience, understanding the patients' experience, learning about
      mental illness from a GP's perspective and changing students' attitudes towards
      mental illness. The students' attitudinal shift comprised 2 main dimensions;
      'normalisation' of mental illness and increased empathy. CONCLUSIONS: Learning
      psychiatry in primary care settings offers students a broader experience of a
      range of patients than in hospital settings and encourages a 'person-centred'
      approach, which in turn can have a positive impact on their attitudes to mental
      illness, reducing stereotyping and increasing empathy.

PMID- 17209899
TI  - Video and qualitative research: analysing medical practice and interaction.
AB  - CONTEXT: Video has long been recognised as providing an important resource within
      medical education, particularly, perhaps, for training in primary health care. As
      a resource for research, and more specifically within qualitative social science
      studies of medical practice, video has proved less pervasive, despite its obvious
      advantages. METHODS: In this paper, we sketch an approach to using video to
      inform the analysis of medical practice and the ways in which health care is
      accomplished through social interaction and collaboration. Drawing on our own
      research, we discuss two brief examples: the first involves the use of computing
      technology in primary health care and the second concerns informal instruction
      during surgery. The examples illustrate the multimodal character of medical work,
      how activities are accomplished through the interplay of talk, the visual and the
      use of material artefacts. They also illustrate the ways in which video provides
      access to the complex forms of social interaction and collaboration that underpin
      health care. DISCUSSION: We reflect upon the research opportunities afforded by
      video and the ways in which video-based studies of interaction can contribute to
      the practice and practicalities of medicine.

PMID- 17209900
TI  - Role of medical professionals and medical education in resource-limited settings
      like India: have we lost sight of the woods in the trees?

PMID- 17209901
TI  - Ethics first.

PMID- 17209902
TI  - Sexual dimorphism in the subadult mandible: quantification using geometric
      morphometrics.
AB  - There have been numerous attempts, with varying degrees of success, to
      differentiate males from females on the basis of the immature skeleton. We
      investigate here whether the mandible can discriminate immature individuals by
      sex; the techniques we apply are from the field of geometric morphometrics. The
      application of these methods in forensic anthropology is still relatively new;
      thus, an important aspect of this research is that it demonstrates potential
      applications in this discipline. The sample comprises 96 known age and sex
      subadult individuals; the three-dimensional coordinates of 38 landmarks are
      analyzed using the shape analysis software morphologika. Multivariate regressions
      indicated no significant sexual dimorphism in the subadult sample; this result is
      supported by poor cross-validated classification accuracy (59%). Our results
      suggest that the subadult mandible is not dimorphic (to the extent that
      dimorphism is not evident within the sample we studied); thus, sex determination
      using previously described criteria is likely to yield poor results.

PMID- 17209903
TI  - Use of the global positioning system in the field recovery of scattered human
      remains.
AB  - This study examines the Global Positioning System (GPS) as a tool for field
      mapping of scattered human remains or other materials in forensic investigations.
      Two aspects of the GPS are considered: (1) the level of accuracy that can be
      obtained using a mid-priced GPS unit, and (2) the effectiveness of using the GPS
      to map scattered materials. The positional accuracy of the GPS receiver was
      tested using a National Geodetic Survey (NGS) point located in Baton Rouge, LA.
      The utility of the GPS for mapping was investigated by setting up a mock field
      recovery and mapping the remains using both the GPS and traditional archeological
      methods. The results indicate that the positional error for a single location
      using GPS was less than one-half meter. However, when multiple positions were
      considered, the data produced on different days were not consistent. Further, the
      GPS receiver used in this study could not distinguish items in close association.
      Factors such as tree cover density, the proximity of the materials to structures
      or trees, and satellite positioning contributed to the erratic data. These
      results indicate that traditional techniques and photographs are still
      indispensable for mapping scattered remains or artifacts.

PMID- 17209904
TI  - Frozen human bone: a microscopic investigation.
AB  - The taphonomic effects of prolonged extreme cold and freezing on human bone have
      received little research attention. Questions of specific interest include
      whether previously frozen bone can be identified and whether freezing alters the
      structural integrity enough to prevent histological aging. There is no evidence
      from previous studies that freezing damages the structural integrity, and to date
      no research investigating the freezing process on bone microstructure has been
      undertaken. This research attempts to distinguish histologically previously
      frozen bone from nonfrozen bone by identifying patterned defects. To determine
      the effects of freezing in bone microstructure using light and scanning electron
      microscopy (SEM), several human bone sections were subjected to prolonged
      freezing and allowed to thaw before thin sectioning. Light microscopy failed to
      demonstrate statistically significant differences between frozen and nonfrozen
      specimens. SEM analysis revealed fractures, although these lacked pattern and did
      not occur systematically throughout the section. Evidence of microstructural
      changes caused by liquid expansion, however, was remarkable but did not alter the
      structural integrity of the microstructure. The results of this study suggest
      that freezing does not alter the process of histomorphological analysis.

PMID- 17209905
TI  - Evaluation of the Suchey-Brooks method for aging skeletons in the Balkans.
AB  - This study has been carried out to examine whether the Suchey-Brooks (S&B)
      methods could be successfully applied in age assessment of populations from the
      Balkans. The known-age sample consists of 33 females and 52 males pairs of pubic
      bones collected from the autopsy cases. Age estimation by S&B method showed an
      accuracy of 89.74% in males and 72.0% in females. Statistical analysis showed a
      positive correlation between the actual age of the investigated individuals and
      age phases obtained by the S&B method, although the mean values of the sixth age
      category differed significantly compared with the original model. The most
      reliable indicators in both sexes were the relief of the symphyseal surface,
      lipping, symphyseal rim, and dorsal margin. The discriminating power of these
      indicators was the least reliable in distinguishing S&B phases 2 and 3. Based on
      these results, the appropriate recommendations for aging Serbian populations are
      made. There was a good agreement between two observers (kappa=0.726).

PMID- 17209906
TI  - Analysis of forensic soil samples via high-performance liquid chromatography and
      ion chromatography.
AB  - Traditional forensic soil comparisons are performed via physical and/or chemical
      examinations of color, texture, and mineral content, leaving any organic- or
      water-soluble fractions unexamined. This study uses high-performance liquid
      chromatography (HPLC) and ion chromatography (IC) to assess the qualitative and
      quantitative variation in these fractions of soil. Soil samples (n=120) were
      collected over the course of 3 weeks from urban, suburban, and rural locations in
      and around Lansing, MI. Additional samples from six of these locations (two
      urban, two suburban, and two rural) were collected once a week for 10 weeks for
      temporal analysis. Nine additional samples, equally spaced over a 1 m(2) grid,
      from these same six locations were collected for spatial analyses. Qualitative
      and quantitative analysis of the resultant chromatograms separated the 120
      samples into 10 groups by HPLC and 23 groups by IC. This study shows that using
      HPLC and IC to analyze the organic- and water-soluble fractions of soil can
      successfully discriminate samples. Quantitative analysis of the results
      eliminates some false inclusions by providing further differentiation of samples.
      The results of this study indicate that adding HPLC and IC analyses to
      traditional forensic soil analysis schemes can improve overall sample
      differentiation. The methods used in this study were also able to detect both
      qualitative and quantitative variations in soil over a relatively small
      geographic area. This demonstration of soil heterogeneity underscores the
      importance of the collection of a representative known sample population when
      assessing a forensic soil comparison. Significant temporal variation was also
      demonstrated over the course of 10 weeks of sampling; however, samples were found
      to be consistent over shorter periods of time. Baseline levels of inorganic
      anions were determined via IC; these levels may be useful in assessing the
      significance of anions detected in soil from cases involving low explosives.

PMID- 17209907
TI  - Value of DNA tests: a decision perspective.
AB  - Before a Court of Law testifying in DNA-evidence cases, scientists are often
      challenged with the idea that the more markers (loci) the better, i.e., why does
      the scientist not use 16 or more markers? This paper introduces a new
      perspective, decision analysis, to deal with the problem of the number of markers
      to type in a criminal context. The decision-making process, which plays a key
      role in the routine work of a forensic scientist, consists of the rational
      choice, given personal objectives, between two or more possible outcomes when the
      consequences of the choice are uncertain. Simulated results support the
      hypothesis that analytical added value does not increase with the number of
      markers.

PMID- 17209908
TI  - Mitochondrial DNA amplification success rate as a function of hair morphology.
AB  - This study examines the amplification success rate of mitochondrial DNA from
      human head hair with respect to their potential for forensic application.
      Mitochondrial DNA was isolated using a Chelex-based extraction method and
      amplified using the LINEAR ARRAY duplex PCR system. The particular focus of this
      study was to characterize the morphological features of human head hair in order
      to further the understanding of the factors that influence amplification success
      rate in hair tissue using the LINEAR ARRAY duplex PCR system. 2554 head hairs
      from 132 individuals representing four population groups were amplified. The hair
      samples were characterized as follows: 1251 were identified microscopically as
      telogen hairs and 1303 were classified as hairs without roots (removed before
      extraction). Amplification success was assessed as a function of several
      independent variables: morphological characteristics; telogen root versus no
      root; donor age; scalp origin; use of cosmetic hair treatments; and race of the
      donor. The results show that a positive correlation exists between amplification
      success and the presence of a telogen root. Combining the amplification success
      with either the original or optimized protocol, telogen hairs result in an
      overall success rate of 77.5% compared with 65% for hairs with no roots.
      Controlling for telogen hairs, the findings indicate that the overall success
      rate is independent of cosmetic hair treatments; medulla structure; shaft length,
      diameter, and volume; and scalp origin. Conversely, the age of the donor, the
      race of the donor, and hair pigmentation all contribute to a variation in
      amplification success rate.

PMID- 17209909
TI  - Infrared spectroscopic imaging for noninvasive detection of latent fingerprints.
AB  - The capability of Fourier transform infrared (FTIR) spectroscopic imaging to
      provide detailed images of unprocessed latent fingerprints while also preserving
      important trace evidence is demonstrated. Unprocessed fingerprints were developed
      on various porous and nonporous substrates. Data-processing methods used to
      extract the latent fingerprint ridge pattern from the background material
      included basic infrared spectroscopic band intensities, addition and subtraction
      of band intensity measurements, principal components analysis (PCA) and
      calculation of second derivative band intensities, as well as combinations of
      these various techniques. Additionally, trace evidence within the fingerprints
      was recovered and identified.

PMID- 17209910
TI  - Computation of likelihood ratios in fingerprint identification for configurations
      of any number of minutiae.
AB  - Recent court challenges have highlighted the need for statistical research on
      fingerprint identification. This paper proposes a model for computing likelihood
      ratios (LRs) to assess the evidential value of comparisons with any number of
      minutiae. The model considers minutiae type, direction and relative spatial
      relationships. It expands on previous work on three minutiae by adopting a
      spatial modeling using radial triangulation and a probabilistic distortion model
      for assessing the numerator of the LR. The model has been tested on a sample of
      686 ulnar loops and 204 arches. Features vectors used for statistical analysis
      have been obtained following a preprocessing step based on Gabor filtering and
      image processing to extract minutiae data. The metric used to assess similarity
      between two feature vectors is based on an Euclidean distance measure. Tippett
      plots and rates of misleading evidence have been used as performance indicators
      of the model. The model has shown encouraging behavior with low rates of
      misleading evidence and a LR power of the model increasing significantly with the
      number of minutiae. The LRs that it provides are highly indicative of identity of
      source on a significant proportion of cases, even when considering configurations
      with few minutiae. In contrast with previous research, the model, in addition to
      minutia type and direction, incorporates spatial relationships of minutiae
      without introducing probabilistic independence assumptions. The model also
      accounts for finger distortion.

PMID- 17209911
TI  - A blind trial evaluation of a crime scene methodology for deducing impact
      velocity and droplet size from circular bloodstains.
AB  - In a previous study, mechanical engineering models were utilized to deduce impact
      velocity and droplet volume of circular bloodstains by measuring stain diameter
      and counting spines radiating from their outer edge. A blind trial study was
      subsequently undertaken to evaluate the accuracy of this technique, using an
      applied, crime scene methodology. Calculations from bloodstains produced on
      paper, drywall, and wood were used to derive surface-specific equations to
      predict 39 unknown mock crime scene bloodstains created over a range of impact
      velocities (2.2-5.7 m/sec) and droplet volumes (12-45 microL). Strong
      correlations were found between expected and observed results, with correlation
      coefficients ranging between 0.83 and 0.99. The 95% confidence limit associated
      with predictions of impact velocity and droplet volume was calculated for paper
      (0.28 m/sec, 1.7 microL), drywall (0.37 m/sec, 1.7 microL), and wood (0.65 m/sec,
      5.2 microL).

PMID- 17209912
TI  - Comparison of the effectiveness of Tenax TA and Carbotrap 300 in concentration of
      flammable liquids compounds.
AB  - The aim of research was to compare two adsorbents, Tenax TA and Carbotrap 300, to
      evaluate their usefulness as passive adsorbents of flammable liquids compounds.
      It was also to determine whether Carbotrap 300 could be used in a passive
      adsorption mode, contrary to manufacturer recommendations. To compare the
      adsorption properties and the thermal desorption efficiency for Tenax TA and
      Carbotrap, the components of test mixture were adsorbed and then
      chromatographically analyzed. The analysis was conducted by means of an automated
      thermal desorber coupled with a gas chromatograph and a mass spectrometer. This
      research established that although these adsorbents significantly differ from
      each other in adsorption properties, each of them can be successfully used for
      passive adsorption of ignitable liquids compounds. Tenax TA turned out to be more
      effective for the adsorption of nonpolar, high-boiling compounds, whereas
      Carbotrap is more effective for polar and volatile compounds. The examined
      adsorbents differ in their susceptibility to thermal desorption. For Carbotrap
      300, after the analysis an additional treatment is required to remove the
      remnants of adsorbed compounds. With Tenax TA, this additional step is not
      necessary because the thermal desorption is sufficiently effective that this
      product is immediately ready for re-use.

PMID- 17209913
TI  - A novel method for the analysis of discharged smokeless powder residues.
AB  - A novel method for the estimation of intermediate-long firing distance range is
      proposed. The method is based on the characterization and chemical analysis of
      the smokeless powder particles on the target. An adhesive lifter is applied to
      collect the suspected gunshot residues (GSRs) from the surface of an object, and
      a Modified Griess Test (MGT) is carried out after alkaline hydrolysis on the
      adhesive lifter. Visualized particles are removed from the adhesive lifter under
      a microscope. Two systems are used for the analysis of organic discharge residues
      from the smokeless powder: (1) gas chromatography/thermal energy analysis
      (GC/TEA) for the analysis of nitroglycerine (NG) and 2,4-dinitrotoluene (2,4
      DNT), (2) gas chromatography/mass spectrometry (GC/MS) for the identification of
      organic components such as DNT, NG, and some stabilizers. By using this procedure
      and confirming that the suspected particles are indeed GSR, one can estimate the
      intermediate-long firing distance of c. 0.75-3 m in the presence of very few
      particles and provide information for the classification of ammunition type in
      casework.

PMID- 17209914
TI  - Visual detection of trace nitroaromatic explosive residue using photoluminescent
      metallole-containing polymers.
AB  - The detection of trace explosives is important for forensic, military, and
      homeland security applications. Detection of widely used nitroaromatic explosives
      (trinitrotoluene [TNT], 2,4-dinitrotoluene [DNT], picric acid [PA]) was carried
      out using photoluminescent metallole-containing polymers. The method of detection
      is through the quenching of fluorescence of thin films of the polymer, prepared
      by spray coating organic solutions of the polymer, by the explosive analyte.
      Visual quenching of luminescence (lambda(em) approximately 400-510 nm) in the
      presence of the explosive is seen immediately upon illumination with near-UV
      light (lambda(ex)=360 nm). Detection limits were observed to be as low as 5 ng
      for TNT, 20 ng for DNT, and 5 ng for PA. In addition, experiments with normal
      production line explosives and their components show that this technology is also
      able to detect composition B, Pyrodex, and nitromethane. This method offers a
      convenient and sensitive method of detection of trace nitroaromatic explosive
      residue.

PMID- 17209915
TI  - Modified cobalt thiocyanate presumptive color test for ketamine hydrochloride.
AB  - A new presumptive color test for ketamine hydrochloride is reported. The test is
      a modification of the cobalt thiocyanate test currently used for cocaine and
      involves basifying samples rather than acidifying them. The two-step procedure
      for liquids and three-step procedure for powdered samples are straightforward,
      definitive, and utilize reagents commonly used in forensic drug analysis. The
      test works on ketamine hydrochloride in both powder and liquid form and has a
      sensitivity of c. 1.25 mg. Performing the test with numerous other controlled
      substances and related chemicals demonstrates the test to be highly selective.

PMID- 17209916
TI  - Quantification of the amphetamine content in seized street samples by Raman
      spectroscopy.
AB  - A Raman spectroscopy method for determining the drug content of street samples of
      amphetamine was developed by dissolving samples in an acidic solution containing
      an internal standard (sodium dihydrogen phosphate). The Raman spectra of the
      samples were measured with a CDD-Raman spectrometer. Two Raman quantification
      methods were used: (1) relative peak heights of characteristic signals of the
      amphetamine and the internal standard; and (2) multivariate calibration by
      partial least squares (PLS) based on second derivative of the spectra. For the
      determination of the peak height ratio, the spectra were baseline corrected and
      the peak height ratio (h(amphetamine at 994 cm(-1) )/h(internal standard at 880
      cm(-1) )) was calculated. For the PLS analysis, the wave number interval of 1300
      630 cm(-1) (348 data points) was chosen. No manual baseline correction was
      performed, but the spectra were differentiated twice to obtain their second
      derivatives, which were further analyzed. The Raman results were well in line
      with validated reference LC results when the Raman samples were analyzed within 2
      h after dissolution. The present results clearly show that Raman spectroscopy is
      a good tool for rapid (acquisition time 1 min) and accurate quantitative analysis
      of street samples that contain illicit drugs and unknown adulterants and
      impurities.

PMID- 17209917
TI  - Real-time polymerase chain reaction quantification of canine DNA.
AB  - The accurate quantification of target DNA is an important step in the short
      tandem repeat analysis of forensic biological samples. By utilizing
      quantification data to control the amount of template DNA in the polymerase chain
      reaction (PCR), forensic scientists can optimize testing and minimize the
      consumption of limited samples. The ability to identify and quantify target DNA
      in mixed-species samples is crucial when it may be overwhelmed by nontarget DNA,
      as in cases of dog attack. We evaluated two quantitative real-time PCR assays for
      dynamic range, species specificity, and inhibition by humic acid. While both
      assays proved to be highly sensitive and discriminating, the Melanocortin-1
      Receptor (MC1R) gene Taqman assay had the advantages of a shorter run time,
      greater efficiency, and safer reagents. In its application to forensic casework,
      the MC1R assay has been advantageous for quantifying dog DNA in a variety of
      mixed-species samples and facilitating the successful profiling of individual
      dogs.

PMID- 17209918
TI  - Run-specific limits of detection and quantitation for STR-based DNA testing.
AB  - STR-based DNA profiling is an exceptionally sensitive analytical technique that
      is often used to obtain results at the very limits of its sensitivity. The
      challenge of reliably distinguishing between signal and noise in such situations
      is one that has been rigorously addressed in numerous other analytical
      disciplines. However, an inability to determine accurately the height of
      electropherogram baselines has caused forensic DNA profiling laboratories to
      utilize alternative approaches. Minimum thresholds established during laboratory
      validation studies have become the de facto standard for distinguishing between
      reliable signal and noise/technical artifacts. These minimum peak height
      thresholds generally fail to consider variability in the sensitivity of
      instruments, reagents, and the skill of human analysts involved in the DNA
      profiling process over the course of time. Software (BatchExtract) made publicly
      available by the National Center for Biotechnology Information now provides an
      alternative means of establishing limits of detection and quantitation that is
      more consistent with those used in other analytical disciplines. We have used
      that software to determine the height of each data collection point for each dye
      along a control sample's electropherogram trace. These values were then used to
      determine a limit of detection (the average amount of background noise plus three
      standard deviations) and a limit of quantitation (the average amount of
      background noise plus 10 standard deviations) for each control sample. Analyses
      of the electropherogram data associated with the positive, negative, and reagent
      blank controls included in 50 different capillary electrophoresis runs validate
      that this approach could be used to determine run-specific thresholds objectively
      for use in forensic DNA casework.

PMID- 17209919
TI  - Evaluation of six presumptive tests for blood, their specificity, sensitivity,
      and effect on high molecular-weight DNA.
AB  - Luminol, leuchomalachite green, phenolphthalein, Hemastix, Hemident, and Bluestar
      are all used as presumptive tests for blood. In this study, the tests were
      subjected to dilute blood (from 1:10,000 to 1:10,000,000), many common household
      substance, and chemicals. Samples were tested for DNA to determine whether the
      presumptive tests damaged or destroyed DNA. The DNA loci tested were D2S1338 and
      D19S433. Leuchomalachite green had a sensitivity of 1:10,000, while the remaining
      tests were able to detect blood to a dilution of 1:100,000. Substances tested
      include saliva, semen, potato, tomato, tomato sauce, tomato sauce with meat, red
      onion, red kidney bean, horseradish, 0.1 M ascorbic acid, 5% bleach, 10% cupric
      sulfate, 10% ferric sulfate, and 10% nickel chloride. Of all the substances
      tested, not one of the household items reacted with every test; however, the
      chemicals did. DNA was recovered and amplified from luminol, phenolphthalein,
      Hemastix, and Bluestar, but not from leuchomalachite green or Hemident.

PMID- 17209920
TI  - Variation in nuclear DNA concentrations during urination.
AB  - This study examined the cellular origin and concentration of nuclear DNA in human
      urine. Ten subjects provided two entire, first-morning voids: one as a single
      specimen and one as a consecutive series of samples. The serial samples were
      centrifuged, organically extracted, and quantified by slot-blot analysis. Total
      DNA concentrations ranged from 0.02 to 21.3 ng/mL for the males and 25.0 to 96.9
      ng/mL for the females. The female samples were found to contain numerous vaginal
      epithelial cells. DNA was detected in all of the serial samples of nine subjects;
      however, the DNA concentrations varied considerably. With six subjects, the DNA
      concentration of the first serial sample was at least three times greater than
      that of the entire void. DNA was only detected in the first 21% of the void from
      one male subject. The results of this study have implications for the collection
      of urine samples.

PMID- 17209921
TI  - Mole guns in Turkey in 2003-2005.
AB  - This study describes the frequency of mole guns in Turkey by examining the cases
      sent to the Council of Forensic Medicine of Turkey between 2003 and 2005. In
      total, 11 mole guns were examined. Mole guns are manufactured to be used as a
      trap against detrimental animals. Although they are not meant to be used as a
      firearm, they are able to cause death. Mole guns appearing in regular casework
      were evaluated in terms of type of the gun, number of barrels, size and caliber,
      rifling, design, mechanism, fitness for use, legality, and geographical
      distribution. Ninety-one percent of the guns were 12 gauge. Most commonly they
      originate from Inner Anatolia. Mole guns are typically handmade. Some examples of
      injuries and deaths caused by mole guns are also offered.

PMID- 17209922
TI  - Pen guns in Turkey.
AB  - This study describes the frequency and type of pen guns in Turkey by examining
      the cases sent to the Council of Forensic Medicine of Turkey between 2000 and
      2004. In total, 32 cases and 61 pen guns were examined. These guns were evaluated
      in respect of the type of the gun, size and caliber, rifling, design, mechanism,
      fitness for use, legality, and geographical distribution. Fifty-nine percent of
      the guns were 22-gauge. Most commonly, they originate from South Eastern
      Anatolia. It is suggested that the guns are handmade.

PMID- 17209923
TI  - Interpretation of automotive light bulb examination results: an intriguing case.
AB  - During the examination of light bulbs from a vehicle involved in a road accident,
      the headlights did not reveal any evidence regarding whether they were energized
      or not. Additionally, a police officer turned the lights on after the accident to
      verify their functioning, thus damaging some of the evidence. By examining the
      vehicle, it was determined that the park lights could provide answers regarding
      the conditions of the headlights. After observations, it was concluded that the
      park lights and headlights were off at the time of the impact. This case report
      demonstrates how important it is to integrate the circumstances surrounding the
      case into the interpretation of the results. Nevertheless, it also demonstrates
      the necessity for examining both the vehicle and all light bulbs in order to
      reach the most pertinent and proper conclusion.

PMID- 17209924
TI  - Role of family factors in adolescent delinquency in an Elazig/Turkey reformatory.
AB  - Family is one of the most important factors in the social and psychological
      progress of an adolescent. Social behavior disorders in childhood have been
      reported to be caused by many factors that may lead children to commit a crime.
      Our study included a total of 106 convicted adolescents from Eastern Turkey in a
      reformatory and 126 unconvicted adolescents with a similar socio-economic status.
      A survey form was completed during a face-to-face interview and a review of
      official records was undertaken. The role of family disruption, education levels
      of parents, the rate of imprisonment among first- and second-degree relatives,
      migration as a family from their place of birth, and the number of delinquent
      children in the family were evaluated. There was a significant difference between
      the conditions in the families of convicted and unconvicted adolescents. Family
      factors play an important role in the development of adolescent delinquency. To
      prevent or decrease this rate of childhood or adolescent delinquency, there needs
      to be an improvement in the socio-cultural conditions of families.

PMID- 17209925
TI  - Value of DNA evidence in detecting crime.
AB  - DNA material is now collected routinely from crime scenes for a wide range of
      offences and the timely processing of the DNA is seen as key to its success in
      investigating and detecting crime. An analysis of DNA material recovered from the
      volume crime offences of residential burglary, commercial burglary, and theft of
      motor vehicle in Northamptonshire, U.K., in 2004 has enabled the DNA to be
      categorized into seven sources. Further analysis using a logistical regression
      has revealed a number of predictors, other than timeliness, that greatly
      influence whether the DNA material recovered from a crime scene enables the crime
      to be detected. The results indicate that a number of these predictors are of
      statistical significance and may be just as relevant in determining whether DNA
      successfully detects the crime as the timeliness of the processing of the DNA
      material. The most significant predictor was found to be investigating officer
      accreditation with location, quantity, and type of DNA material at the crime
      scene also being relevant. Accreditation of the Crime Scene Examiner recovering
      the DNA material was found not to be significant. Consideration is given to where
      further emphasis is needed by the U.K. police service to maximize the
      opportunities to detect volume crime with DNA.

PMID- 17209926
TI  - Child abduction murder: an analysis of the effect of time and distance separation
      between murder incident sites on solvability.
AB  - Empirical studies of child abduction murder investigations are lacking.
      Accordingly, an empirical analysis of the effect of time and distance
      relationships on case solvability in child abduction murders (N=735) was
      conducted. The murders occurred across the United States from 1968 to 2002.
      Murder incident components examined were: victim last seen site, initial contact
      site, murder site, and body recovery site. Time and distance intervals between
      component pairings were also examined. Descriptive, bivariate, and multivariate
      analyses were performed to determine if information relating to time and distance
      intervals between components were critical solvability factors. Results show that
      information about time and distance increases case solvability. Results also
      demonstrate that time and distance relationships contribute uniquely to case
      solvability in murders of abducted children. Findings also indicate that
      additional factors such as type of forensic evidence, investigative resources, or
      actions by first responders, may be critical to case solvability.

PMID- 17209927
TI  - Usefulness of combining clinical and radiological dental findings for a more
      accurate noninvasive age estimation.
AB  - The aim of this study was to establish correlations of clinical and radiological
      dental findings, alone or in combination, with chronological age in adults.
      Dental findings and orthopantomograms of 984 patients (aged 20-60 years; 524
      females/460 males) were analyzed. DMF-T index and distance (alveolar bone level,
      ABL) between cemento-enamel junction and alveolar bone margin were recorded.
      Additionally, clinical and radiological findings at each tooth crown and root
      were collected according to the actual status of destruction and restoration, and
      a total score for each dentition (TSD) was calculated. After univariate
      correlation analysis, correlation coefficients for ABL and TSD were improved by
      using square root (sqrt). However, the determination accuracy was still not
      satisfactory; 90% of the residuals were in the range of about +/-10. The present
      study showed that clinical and radiological dental findings could not be used,
      not even in combination, for accurate age estimation as a single method, but that
      they could support other methods.

PMID- 17209928
TI  - Effectiveness of comparison overlays generated with DentalPrint software in bite
      mark analysis.
AB  - Validation studies of the new DentalPrint software were carried out with
      experimental bite marks in pigskin. The bite marks were digitally photographed
      according to the ABFO guidelines for evidence collection. Dental casts used in
      the experiment were scanned in 3D and 2D, and comparison overlays were generated
      using DentalPrint and Adobe Photoshop software, respectively. Digitized
      photographs of the experimental bite marks and the biting edges obtained in the
      overlays were compared by two different examiners to analyze the impact of
      training and experience with the two methods. Receiver operating characteristic
      (ROC) analysis, sensitivity, specificity, and 95% confidence intervals for each
      cutoff point were calculated. The expert examiner using DentalPrint obtained the
      best results, with an area under the ROC curve of 0.76 (SE=0.057; CI at 95%=0.652
      0.876). Fairly high specificity values were found for DentalPrint, and the best
      results were obtained for the cutoff value that discriminated between the
      examiner's response "biter" and the rest of the possible (specificity 97.9%, CI
      at 95%=93.2%-99.6%). Therefore, the results presented here indicate that
      DentalPrint is a useful, accurate tool for forensic purposes, although further
      research on the comparison process is needed to enhance the validity of bite mark
      analysis.

PMID- 17209929
TI  - Identification through X-ray fluorescence analysis of dental restorative resin
      materials: a comprehensive study of noncremated, cremated, and processed-cremated
      individuals.
AB  - Tooth-colored restorative materials are increasingly being placed in the practice
      of modern dentistry, replacing traditional materials such as amalgam. Many
      restorative resins have distinct elemental compositions that allow identification
      of brand. Not only are resins classifiable by elemental content, but they also
      survive extreme conditions such as cremation. This is of significance to the
      forensic odontologist because resin uniqueness adds another level of certainty in
      victim identification, especially when traditional means are exhausted. In this
      three-part study, unique combinations of resins were placed in six human cadavers
      (total 70 restorations). Simulated ante-mortem dental records were created. In a
      blind experiment, a portable X-ray fluorescence (XRF) unit was used to locate and
      identify the resin brands placed in the dentition. The technique was successful
      in location and brand identification of 53 of the restorations, which was
      sufficient to enable positive victim identification among the study group. This
      part of the experiment demonstrated the utility of portable XRF in detection and
      analysis of restorative materials for victim identification in field or morgue
      settings. Identification of individuals after cremation is a more difficult task,
      as the dentition is altered by shrinkage and fragmentation, and may not be
      comparable with a dental chart. Identification of processed cremains is a much
      greater challenge, as comminution obliterates all structural relationships. Under
      both circumstances, it is the nonbiological artifacts that aid in identification.
      Restorative resin fillings can survive these conditions, and can still be named
      by brand utilizing elemental analysis. In a continuation of the study, the
      cadavers were cremated in a cremation retort under standard mortuary conditions.
      XRF was again used to analyze retrieved resins and to identify the individuals
      based on restorative materials known to exist from dental records. The cremains
      were then processed and the analysis was repeated to determine whether
      restorative resins could be found under this extreme condition. Under both
      circumstances, sufficient surviving resin material was found to distinguish
      positively each individual in the study group. This study showed the utility of
      XRF as an analytical tool for forensic odontology and also the significance of
      the role of restorative resins in victim identification, even after cremation.

PMID- 17209930
TI  - Age estimation by pulp/tooth ratio in canines by peri-apical X-rays.
AB  - Estimation of age in individuals has received considerable attention in forensic
      science, in which it is a widely used method for individual identification,
      together with paleo-demographic analyses to establish mortality patterns in past
      populations. The present investigation, which is a continuation of a previously
      published pilot study, was conducted to examine the possible application of the
      pulp/tooth area ratio by peri-apical images as an indicator of age at death. A
      total of 200 peri-apical X-rays of upper and lower canines were assembled from 57
      male and 43 female skeletons of Caucasian origin, aged between 20 and 79 years.
      They belong to the Frassetto osteological collection of Sassari (Sardinia) and
      are housed in the Museum of Anthropology, Department of Experimental and
      Evolutionistic Biology, University of Bologna. For each skeleton, dental maturity
      was evaluated by measuring the pulp/tooth area ratio on upper (x(1)) and lower
      (x(2)) canines. Very good agreement was found between intraobserver measurements.
      Statistical analysis was performed in order to obtain multiple regression
      formulae for dental age calculation, with chronological age as dependent
      variable, and gender, and upper and lower canines as independent variables.
      Stepwise regression analysis showed that gender did not contribute significantly
      to the fit (p=0.881) whereas variables x(1) and x(2) and the first-order
      interaction between them did. These two variables explained 92.5% of variations
      in estimated chronological age and the residual standard error was 4.06 years.
      Lastly, two simple linear regression equations were obtained for age estimation
      using canines from the maxilla and mandible separately. Both models explained 86%
      of variations in estimated chronological age and allowed an age-at-death estimate
      with a residual standard error of about 5.4 years.

PMID- 17209931
TI  - Ventilatory and metabolic demands during aggressive physical restraint in healthy
      adults.
AB  - We investigated ventilatory and metabolic demands in healthy adults when placed
      in the prone maximal restraint position (PMRP), i.e., hogtie restraint. Maximal
      voluntary ventilation (MVV) was measured in seated subjects (n=30), in the PMRP,
      and when prone with up to 90.1 or 102.3 kg of weight on the back. MVV with the
      heaviest weight was 70% of the seated MVV (122+/-28 and 156+/-38 L/min,
      respectively; p<0.001). Also, subjects (n=27) were placed in the PMRP and
      struggled vigorously for 60 sec. During the restrained struggle, ventilatory
      function (V(E)/ MVV) was 44% of MVV in the resting PMRP. While prone with up to
      90.1 or 102.3 kg on the back, the decrease in MVV was of no clinical importance
      in these subjects. Also, while maximally struggling in the PMRP, V(E) was still
      adequate to supply the ventilatory needs.

PMID- 17209932
TI  - Deaths associated with choking in San Diego county.
AB  - Death from choking is the fourth most common cause of unintentional-injury
      mortality, but little data are published on causes or locations of these
      episodes. These deaths typically are peaked at the extremes of age, with young
      children and the elderly having the greatest rate of fatal choking. Our objective
      was to characterize the causes of fatal airway obstruction in adults. The San
      Diego County Medical Examiner's database was searched for deaths attributed to
      choking in decedents 18 years and older during the 10-year period from 1994 to
      2004. Data were abstracted regarding the underlying medical conditions, items
      choked on, location of the choking, and treatments involved in the individual
      cases. We found 133 victims who died from choking, with 14% having using alcohol
      or other sedatives and 55% having a documented neurological deficit or anatomic
      difficulty with swallowing. The most common specified food objects that victims
      choked on were meat products, and 45% occurred at home, followed by 26% at
      supervised facilities, and 14% at restaurants. Of the 19 choking episodes
      occurring in restaurants, only one employee was documented to attempt a
      resuscitative effort. Most victims who choked to death had an underlying
      neurological deficit, and occurred at home or supervised facilities appear to
      have an appropriate initial-response intervention.

PMID- 17209933
TI  - Diagnostic dilemma of sudden deaths due to acute hemorrhagic pancreatitis.
AB  - Sudden death due to acute pancreatitis has been rarely determined. A review of
      3305 autopsies performed between 1991 and 2001 at the Council of Forensic
      Medicine found 12 cases (0.36%) with sudden death due to acute hemorrhagic
      pancreatitis without symptoms. A history of chronic alcohol ingestion was
      obtained from family in four cases (33%), and no stones were found in the bile
      ducts or in the gall bladders. During the autopsies, hemorrhage and edema were
      localized on the head of the pancreas in three cases and the whole pancreas in
      nine cases. The most common extrapancreatic pathology was found in the lung
      including pulmonary edema, alveolar hemorrhage, pleural effusion, and pulmonary
      congestion. There was no correlation between pulmonary and pancreatic damage. It
      is suggested that the forensic pathologists who are dealing with sudden
      unexpected death must not ignore the examination of pancreatic and
      extrapancreatic regions to avoid missing acute pancreatitis.

PMID- 17209934
TI  - Infant death due to air embolism from peripheral venous infusion.
AB  - An otherwise healthy male infant was brought to the hospital because the mother
      suspected superficial infection at the operative site 5 days after an inguinal
      hernia repair. He was admitted to the pediatric unit overnight to be evaluated by
      his surgeon the next morning. When a venous infusion of maintenance fluids was
      started, the patient immediately went into cardio-respiratory arrest and was
      pronounced dead after resuscitation efforts failed. Subsequently, air collections
      were found in both venous and arterial circulations, including the splenoportal
      system. Detailed review of the clinical presentation and course, laboratory
      results, radiological, and pathological findings, along with a review of
      pertinent literature provides an explanation for the death by air embolism.
      Apparent inconsistent findings both radiographically and at autopsy are resolved.
      The mechanism of distribution of air to both systemic and splenoportal
      circulation is discussed. We believe this to be only the eighth case reported in
      English-language literature of infantile death from peripheral venous infusion.
      In all age groups, we find only six other cases in the English-language
      literature of gas found concomitantly in both the systemic and portal venous
      systems.

PMID- 17209935
TI  - Brain arteriovenous malformation and its implication in forensic pathology.
AB  - Despite the fact that brain arteriovenous malformations (BAVMs) are a possible
      cause of sudden and unexplained death, very few papers have discussed their
      importance in the forensic context. BAVMs consist of tangled masses of tortuous
      arteries and veins devoid of intervening capillaries that frequently extend from
      brain parenchyma into the subarachnoid space. Apart from BAVMs, three major
      groups of vascular malformations of the brain are known: cavernous hemangioma,
      venous angioma, and capillary telangiectasia. BAVMs and cavernous hemangioma
      often cause hemorrhages, while venous angioma and capillary telangiectasia are
      typically asymptomatic. Presented here is the case of a 14-year-old girl who died
      from a ruptured BAVM. The present case is a reminder that the forensic
      pathologist should be able to recognize BAVMs and to differentiate it from other
      types of vascular malformations. Although rare, it is a cause of sudden death not
      to be overlooked, especially in children.

PMID- 17209936
TI  - Suicidal decapitation using a tractor loader: a case report and review of the
      literature.
AB  - In forensic practice, decapitated bodies are predominantly associated with
      decapitation by wheels of trains or with postmortem dismemberment following
      homicide. In the suicidal context, decapitation accounts for less than 1% of
      total suicide. Apart from decapitation by trains, other encountered methods
      involve suicidal hanging and vehicle-assisted ligature suicide. Reported here is
      a unique case of suicidal decapitation in a 45-year-old man using a tractor
      loader at the foot of a silo, on his farm. The head was recovered in the loader
      and there were several impact spots from the loader as well as blood on the silo
      wall. The autopsy revealed a complete decapitation wound with the severance plane
      located between the third and fourth cervical vertebra. A 1.5 cm wide abrasion on
      the anterior part of the neck and abrasions under the chin were noted. This very
      unique case of intentional suicidal decapitation is the first reported case of a
      planned system intended to create decapitation outside the unique case of
      homemade guillotine and the more common decapitation by train.

PMID- 17209937
TI  - A new type of shotgun ammunition produces unique wound characteristics.
AB  - The Tucson Police Department, Tucson, AZ, has begun using the Polyshok Impact
      Reactive Projectile (IRP), a new type of shotgun ammunition that includes a lead
      bead core that travels within single, plastic-encased projectile. On impact, the
      core is released to distribute over a small area, thereby disintegrating on
      impact to reduce the likelihood of exit or collateral damage on missed shots.
      After a brief review of shotgun slug ballistics and wound characteristics and a
      discussion of the mechanism of the Polyshok IRP, we report the first death in the
      United States from this ammunition. Findings included a single entrance wound
      with plastic ammunition components and small lead particles recovered from the
      body, the combination of which normally would suggest a close-range shooting with
      birdshot. However, the characteristics of this ammunition create different
      patterns than are found with slugs or shot, so that a medical examiner unfamiliar
      with the Polyshok IRP could draw inaccurate conclusions about ammunition and
      range of fire. Because the single projectile fired from this ammunition is
      composed of both plastic and lead, plastic components are likely to be found
      within the wound at any range of fire, unlike traditional shot or slug
      ammunition. Also, the small size of lead particles found spread through the wound
      cavity would ordinarily suggest a small-size shot, whereas the external
      appearance of the wound (a single entrance with no dispersion of shot) and the
      pattern of tissue destruction are more consistent with the patterns of injury
      associated with shotgun slugs.

PMID- 17209938
TI  - Paths to destruction: the lives and crimes of two serial killers.
AB  - Although research into the phenomenon of serial murder has revealed that serial
      killers frequently do not fit the initially described paradigm in terms of their
      physical and psychological profiles, backgrounds, and motives to kill, the media
      continues to sensationalize the figures of such killers and the investigators who
      attempt to analyze them on the basis of aspects of their crimes. Although the so
      called "typical" profile of the serial murderer has proven accurate in some
      instances, in many other cases the demographics and behaviors of these killers
      have deviated widely from the generalized assumptions. This report details two
      unusual cases in which five and eight murders were committed in upstate New York.
      The lives and crimes of these offenders illustrate the wide spectrum of
      variations in the backgrounds, demographics, motivations, and actions witnessed
      among serial murderers, and highlight the limitations and dangers of profiling
      based on generalities.

PMID- 17209939
TI  - The hooligan's mind.
AB  - Football hooliganism is a world phenomenon and an everyday matter. Society spends
      a lot of money to prevent and control it. We need to know what hooligans think in
      order to anticipate their actions and prevent their violent behaviors. In this
      paper, I propose a theory of the hooligan's conscious mind, by analyzing the
      thinking of a real Italian hooligan who was my patient. I will show that violent
      behaviors of hooligans are not unconscious, because the mental states (both
      beliefs and goals) of hooligans are explicitly represented in their mind. In
      contrast, I will suggest that both supporting and fighting are planned (i.e.,
      goal directed), because "recognized supremacy" is explicitly represented as the
      ultimate goal. In fact, hooligans support and fight in order to be recognized as
      good hooligans, i.e. as good supporters as well as good fighters.

PMID- 17209940
TI  - Ballpoint pen inks: the quantitative analysis of ink solvents on paper by solid
      phase microextraction.
AB  - We wish to describe further developments to a method previously reported on the
      detection of 2-phenoxyethanol in ink. The solid-phase microextraction (SPME)
      sampling technique, together with gas chromatography-mass spectrometry (GC-MS),
      has been used to quantify solvents in writing ink. In conventional approaches,
      the analysis of ink on documents requires some degree of destructive sampling.
      The methods commonly used remove ink samples from paper using a scalpel or a
      paper punch. To avoid document destruction, a sampling cell was constructed that
      allows solvents to be adsorbed directly onto the SPME fiber from the headspace
      above the document surface. Analytes (ink volatiles) are then desorbed from the
      SPME fiber on a gas chromatograph equipped with a mass selective detector (GC
      MSD). With this method, it was possible to detect the presence of ink solvents on
      documents for a period lasting up to c. 2 years.

PMID- 17209941
TI  - Differentiation of blue ballpoint pen inks by laser desorption ionization mass
      spectrometry and high-performance thin-layer chromatography.
AB  - The differentiation of inks on a questioned document can highlight a fraudulent
      insertion and is usually carried out by optical comparison and thin-layer
      chromatography (TLC). Laser desorption ionization mass spectrometry (LDI-MS) may
      also be used for the analysis of dyes from ink. This analytical technique was
      compared with a standard method of high-performance TLC (HPTLC) according to
      their capacity to differentiate blue ballpoint inks. Ink entries on paper from 31
      blue ballpoint pens have been analyzed and their dye ink formulations compared.
      The pens were classified into 26 classes by LDI-MS against 18 for HPTLC. LDI-MS
      proved to be a more powerful method for differentiating ink formulations because
      it provides information about dye structures (molecular weights) and relative
      quantification of dye classes (peak areas). Sample preparation was minimal and
      analysis time was short in contrast to the more complex extraction, application,
      and development steps of the HPTLC method. However, only basic dyes and pigments
      were identified using positive mode LDI-MS, while HPTLC did yield additional
      information about acid dyes.

PMID- 17209942
TI  - Fatal mephenesin intoxication.
AB  - This report describes a death related to the abuse of and intoxication by
      mephenesin. To the best of our knowledge, this is the first report case of lethal
      intoxication involving solely mephenesin and reporting mephenesin blood
      concentrations. The victim was a 48-year-old woman found unconscious at home.
      Resuscitation was unsuccessful. Toxicological analysis was performed on a blood
      sample collected during resuscitation. The results being negative, the body was
      exhumed for an autopsy, which revealed bronchial inhalation syndrome. Analysis in
      a second laboratory has revealed the presence of mephenesin in samples collected
      during autopsy. No other drug/toxin was found, and alcohol was negative.
      Reanalysis of the peripheral blood collected during resuscitation found a
      mephenesin concentration of 15.81 microg/mL (15-fold greater that the maximum
      concentration that would result from a single intake of a 500 mg formulation).
      The pathologist has concluded on a bronchial inhalation syndrome consecutive to a
      mephenesin overdose as the cause of death. The manner of this death is discussed
      in the light of the toxicological hair analysis and the medical past of the
      victim.

PMID- 17209943
TI  - Letter to the editor--artifactual vitreous methanol concentration.

PMID- 17209944
TI  - Allele frequencies for two STR loci D6S1274 and D17S1299 in Chinese and Thai
      populations.

PMID- 17209945
TI  - Allele frequency of D13S325 and D13S892 in two populations.

PMID- 17209946
TI  - Allele frequencies for two short tandem repeat loci in the Chinese Han population
      from Chengdu, China, and a Thai population from Thailand.

PMID- 17209947
TI  - Southwest China Han Population data for nine Y-STR loci by multiplex polymerase
      chain reaction.

PMID- 17209948
TI  - STR data for the AmpFlSTR Identifiler loci from the three main ethnic indigenous
      population groups (Iban, Bidayuh, and Melanau) in Sarawak, Malaysia.

PMID- 17209949
TI  - 6 Y-SNP typing of China and Korean samples using primer extension and DHPLC.

PMID- 17209950
TI  - Distribution of D2S2958, D2S1769, and D18S872 alleles in a Chinese population
      sample.

PMID- 17209951
TI  - Genotype profile for fifteen tetranucleotide repeat loci in two Tibeto-Burman
      speaking tribal populations of Arunachal Pradesh, India.

PMID- 17209954
TI  - FDA approval of totally implantable permanent total artificial heart for
      humanitarian use.

PMID- 17209955
TI  - Behavior of cardiomyocytes and skeletal muscle cells on different extracellular
      matrix components--relevance for cardiac tissue engineering.
AB  - Myocardial cell transplantation in patients with heart failure is emerging as a
      potential therapeutic option to augment the function of remaining myocytes.
      Nevertheless, further investigations on basic issues such as ideal cell type
      continue to be evaluated. Therefore, the aim of our studies was to compare the
      performance of skeletal muscle cells and cardiomyocytes with respect to their
      proliferation rate and viability on different extracellular matrix components
      (EMCs). Rat cardiomyocytes (RCM) and rat skeletal muscle cells (RSMC) were
      cultured on EMCs such as collagen type I, type IV, laminin, and fibronectin. The
      components were used as "single coating" as well as "double coating."
      Proliferation rates were determined by proliferation assays on days 1, 2, 4, and
      8 after inoculation of the cells. The most essential result is that collagen type
      I enhances the proliferation rate of RSMC but decreases the proliferation of RCM
      significantly. This effect is independent of the second EMC used for the double
      coating studies. Other EMCs also influence cellular behavior, whereas the
      sequence of the EMCs is essential. Results obtained in our studies reveal the
      significant different proliferation behavior of RCM and RSMC under identical
      conditions. As skeletal muscle cells are also used in heart tissue engineering
      models, these results are essential and should be investigated in further studies
      to prove the applicability of skeletal muscle cells for heart tissue engineering
      purposes.

PMID- 17209956
TI  - Electrically conductive biodegradable polymer composite for nerve regeneration:
      electricity-stimulated neurite outgrowth and axon regeneration.
AB  - Normal and electrically stimulated PC12 cell cultures and the implantation of
      nerve guidance channels were performed to evaluate newly developed electrically
      conductive biodegradable polymer composites. Polypyrrole (PPy) doped by butane
      sulfonic acid showed a significantly higher number of viable cells compared with
      PPy doped by polystyrenesulfonate after a 6-day culture. The PC12 cells were left
      to proliferate for 6 days, and the PPy-coated membranes, showing less initial
      cell adherence, recorded the same proliferation rate as did the noncoated
      membranes. Direct current electricity at various intensities was applied to the
      PC12 cell-cultured conductive membranes. After 7 days, the greatest number of
      neurites appeared on the membranes with a current intensity approximating 1.7-8.4
      microA/cm. Nerve guidance channels made of conductive biodegradable composite
      were implanted into rats to replace 8 mm of sciatic nerve. The implants were
      harvested after 2 months and analyzed with immunohistochemistry and transmission
      electron microscopy. The regenerated nerve tissue displayed myelinated axons and
      Schwann cells that were similar to those in the native nerve. Electrical
      stimulation applied through the electrically conductive biodegradable polymers
      therefore enhanced neurite outgrowth in a current-dependent fashion. The
      conductive polymers also supported sciatic nerve regeneration in rats.

PMID- 17209957
TI  - A novel device for reducing hemolysis provoked by cardiotomy suction during open
      heart cardiopulmonary bypass surgery: a randomized prospective study.
AB  - Since the inception of cardiopulmonary bypass (CPB), little progress has been
      made concerning the design of cardiotomy suction (CS). Because this is a major
      source of hemolysis, we decided to test a novel device (Smartsuction [SS])
      specifically aimed at minimizing hemolysis during CPB in a clinical setting.
      Block randomization was carried out on a treated group (SS, n=28) and a control
      group (CTRL, n=26). Biochemical parameters were taken pre-, peri-, and post CPB
      and were compared between the two groups using the Student's t-test with
      statistical significance when P<0.05. No significant differences in patient
      demographics were observed between the two groups. Lactate dehydrogenase (LDH)
      and plasma free hemoglobin (PFH) pre-CPB were comparable for the CTRL and SS
      groups, respectively. LDH peri-CPB was 275+/-100 U/L versus 207+/-83 U/L for the
      CTRL and SS groups, respectively (P<0.05). PFH was 486+/-204 mg/L versus 351+/
      176 mg/L for the CTRL and SS groups, respectively (P<0.05). LDH post CPB was
      354+/-116 U/L versus 275+/-89 U/L for the CTRL and SS groups, respectively
      (P<0.05). PFH was 549+/-271 mg/L versus 460+/-254 mg/L for the CTRL and SS
      groups, respectively (P<0.05). Preoperative hematocrit (Hct) of 43+/-5% (CTRL)
      versus 37+/-5% (SS), and hemoglobin (Hb) of 141+/-16 g/L (CTRL) versus 122+/-17
      g/L (SS) were significantly lower in the SS group. However, when normalized (N),
      the SS was capable of conserving Hct, Hb, and erythrocyte count perioperatively.
      Erythrocytes (N) were 59+/-5% (CTRL) versus 67+/-9% (SS); Hct (N) was 59+/-6%
      (CTRL) versus 68+/-9% (SS), and Hb (N) was 61+/-6% (CTRL) versus 70+/-10% (SS)
      (all P<0.05). This novel SS device evokes significantly lowered blood PFH and LDH
      values peri- and post CPB compared with the CTRL blood using a CS system. The SS
      may be a valuable alternative compared to traditional CS techniques.

PMID- 17209958
TI  - The acute effect of intra-aortic balloon counterpulsation during extracorporeal
      life support: an experimental study.
AB  - Hemodynamically unstable patients supported by an extracorporeal life support
      (ECLS) circuit often receive additional support by intra-aortic balloon pump
      (IABP). However, it is not established whether support of the failing heart is
      improved by adjunctive IABP in both peripheral cannulation (PC) and central
      cannulation (CC) settings. Seven sheep were supported by an IABP and an ECLS
      system which were cannulated centrally as well as peripherally. In each
      cannulation configuration, hemodynamic and cardiac function indices were measured
      at baseline, ECLS, and ECLS plus IABP. The primary variables were mean coronary
      artery flow (Qcor), diastolic pressure time index (DPTI), left ventricular (LV)
      pressure-volume area (PVA), and tension time index (TTI). Additional IABP with
      ECLS support (CC/PC) decreased LV afterload (LV systolic peak pressure -4%,
      P<0.05/-8%, P<0.02), as well as TTI -2%/-10% and PVA -10%/-12% (P<0.03). Coronary
      perfusion was increased by additional IABP: CC, Qcor, +9%, and DPTI, +18%
      (P<0.02); PC, Qcor,+6%, and DPTI, +11% (P<0.05). IABP augmented the myocardial
      oxygen supply/demand ratios (CC/PC): Qcor/(PVA.heart rate) (+21%/+22%, P<0.02)
      and DPTI/TTI (+27%/+24%, P<0.03). In case of low arterial pressure (<50 mm Hg)
      and reduced ECLS flow, the overall hemodynamic profile improved only with central
      cannulation. We conclude that in both central and peripheral ECLS cannulation
      settings, adjunctive IABP improves the myocardial oxygen supply demand balance.
      In case of low cardiac output and insufficient extracorporeal flow with PC,
      adjunctive IABP may be contraindicated.

PMID- 17209959
TI  - Efficacy and mechanisms of biventricular and left/right direct cardiac
      compression in acute heart failure sheep.
AB  - Direct cardiac compression (DCC) with implanted heart patches has previously
      demonstrated efficacy of biventricular (BiV) support in acute heart failure (HF)
      sheep. We hypothesized that this was primarily due to a left ventricular (LV)
      effect. This study compared BiV, LV, and right ventricular (RV) assists in terms
      of hemodynamic and energetic response. Ten sheep underwent instrumentation and
      device implantation at least 1 week prior to study. HF (50% reduction in cardiac
      output) was maintained with intravenous esmolol infusion. BiV, LV, and RV assists
      were activated randomly with intervening stable HF periods. BiV assist was more
      effective than either LV or RV assist in restoring hemodynamic parameters;
      however, there was no difference in efficacy of LV and RV support. RV assist
      preserved left coronary flow patterns and chamber geometry compared to other
      assist conditions, but increased LV preload. These results suggest that LV and RV
      support each make a significant contribution to the efficacy of BiV assist,
      albeit through different mechanisms.

PMID- 17209960
TI  - Noninvasive average flow estimation for an implantable rotary blood pump: a new
      algorithm incorporating the role of blood viscosity.
AB  - The effect of blood hematocrit (HCT) on a noninvasive flow estimation algorithm
      was examined in a centrifugal implantable rotary blood pump (iRBP) used for
      ventricular assistance. An average flow estimator, based on three parameters,
      input electrical power, pump speed, and HCT, was developed. Data were collected
      in a mock loop under steady flow conditions for a variety of pump operating
      points and for various HCT levels. Analysis was performed using three-dimensional
      polynomial surfaces to fit the collected data for each different HCT level. The
      polynomial coefficients of the surfaces were then analyzed as a function of HCT.
      Linear correlations between estimated and measured pump flow over a flow range
      from 1.0 to 7.5 L/min resulted in a slope of 1.024 L/min (R2=0.9805). Early
      patient data tested against the estimator have shown promising consistency,
      suggesting that consideration of HCT can improve the accuracy of existing flow
      estimation algorithms.

PMID- 17209961
TI  - Assessment of health-related quality of life in patients treated with
      hemodialysis in Serbia: influence of comorbidity, age, and income.
AB  - The importance of measuring health-related quality of life (HRQoL) in patients on
      maintenance hemodialysis (HD) is being increasingly recognized, but few studies,
      especially from the Balkan region, have addressed this issue. The aims of this
      study were (i) to evaluate HRQoL in an outpatient university-affiliated dialysis
      facility in South Serbia; (ii) to determine the effects of age, presence of
      comorbidity, primary kidney disease, dose of HD, and family income; and (iii) to
      make comparisons of the HRQoL in Serbian patients on chronic HD with that
      reported by others previously. The study enrolled 192 patients on HD for more
      than 3 months. Comorbidity was assessed using the index of coexistent diseases
      (ICED), including two subindexes: index of disease severity (IDS) and index of
      physical impairment (IPI). Patient's self-assessment of HRQoL was measured by the
      36-item short form health survey questionnaire (SF-36), encompassing eight
      summary scales and two summary dimensions. Ten of the baseline variables had
      significant associations with parameters of HRQoL. Fitting these variables in
      linear regression models resulted in 41.9% variance for physical dimension of
      HRQoL (physical component summary score [PCS]), and 32.5% for mental dimension of
      HRQoL (mental component summary score [MCS]). However, statistically significant
      effect had only IDS, IPI, and age for PCS, and income of patients for MCS. We
      found that an increase in IDS score for one unit is associated with a decrease of
      PCS by 13.2%, and SF-36 score (total quality of life) by 15.2%. The increase of
      IPI score by one unit decreases PCS by 16.1% and SF-36 score by 17.5%. A 5-year
      increase in age is associated with a decrease of PCS by 3.1%, and SF-36 score by
      3.8%. The monthly income increase of 10 euros per family member increases MCS by
      5.2% and SF-36 score by 3.0%. HRQoL in patients on HD was found markedly
      impaired. Comorbid conditions have negative and statistically significant
      correlation with parameters of HRQoL, and could explain poor HRQoL to a
      remarkable extent. Older age and poor income substantially reduce HRQoL in HD
      patients.

PMID- 17209962
TI  - An integrative description of dialysis adequacy indices for different treatment
      modalities and schedules of dialysis.
AB  - Dialysis adequacy indices that are applied for the evaluation of the efficiency
      of urea removal include fractional water volume cleared from urea during dialysis
      (KT T/V), fractional solute removal (FSR), and equivalent urea clearance (EKR).
      Using a constant-volume, one-compartment urea kinetic model for an anuric
      patient, the FSR and EKR are shown to depend on only three nondimensional
      parameters: (i) KT/V, where K is the dialyzer clearance for hemodialysis (HD) or
      peritoneal mass transport coefficient for peritoneal dialysis (PD), T is the time
      period of dialysis, and V is urea distribution volume; (ii) T/Tc, where Tc is the
      length of treatment cycle; and (iii) VD/V, where VD is the volume of dialysis
      fluid applied. In particular, analytical formulas for FSR and EKR, valid for HD
      as well as for PD, were derived as functions of these three parameters. Numerical
      simulations, performed using a two-compartment urea kinetic model, showed that
      the analytical formulas are valid also for the two-compartment model, except for
      short, highly effective HD, where the overestimation of FSR and EKR using the
      analytical formulas is however, not higher than 20 and 16%, respectively. KT T/V
      is equal to KT/V for HD and FSR for PD. Thus, our formulas provide an integrative
      description of the relationships between dialysis efficiency indices and
      operational dialysis parameters that is valid for all modalities and schedules of
      dialysis. They may be applied not only for standard HD and continuous ambulatory
      PD, but also for HD with circulating dialysis fluid or intermittent forms of PD.

PMID- 17209963
TI  - "Less stented" bovine pericardial xenograft: a new concept.
AB  - The in vitro hemodynamic behavior of a bovine pericardium xenograft with
      discontinuity of the annular support, named the "Less Stented" bovine pericardial
      xenograft, was analyzed. A "Less Stented" bovine pericardial xenograft consisting
      of a glutaraldehyde-treated bovine pericardium prosthesis manufactured in Braile
      Biomedica Ltd, Sao Jose do Rio Preto, Sao Paulo, Brazil, was used according to
      the same protocols of the stented bioprosthesis manufacturer. Bovine pericardial
      xenografts were tested in a pulse simulator and analyzed in a cardiac simulator,
      with respect to the transvalvular gradient, regurgitant fraction and leakage
      volume, discharge coefficient, performance, and efficiency index. Analyses were
      performed by Pearson's correlation test and simple linear regression. The
      transvalvular gradients ranged between 6.37 and 11.62 mm Hg with a mean flow
      between 4.39 and 7.96 L/min, giving a good correlation (0.8291) on the regression
      curve with an increase in flow. The regurgitant fraction ranged between 10.95 and
      17.94% and leakage volume between 4.49 and 7.87%. The discharge coefficient,
      performance, and efficiency index showed favorable behavior with the flow
      increase, with good correlation coefficient (0.9385, 0.9332, and 0.9024,
      respectively). The initial results of the "Less Stented" bovine pericardial
      xenograft size 25 analyses demonstrated a satisfactory in vitro performance.
      Evaluations of the hemodynamic performance of small size "Less Stented" bovine
      pericardial xenograft should be made to clarify the biological behavior of this
      new xenograft.

PMID- 17209964
TI  - Numerical simulation of hemodynamic changes during beating-heart surgery:
      analysis of the effects of cardiac position alteration in an animal model.
AB  - Hemodynamic instability, mostly due to vertical lifting of the heart, is usually
      observed during beating-heart surgical procedures. However, some hemodynamic
      parameters, such as coronary blood flow, are not routinely measured. A digital
      computer model of the circulation able to simulate and analyze the effects of
      heart lifting and the Trendelenburg maneuver, and thus supply detailed
      hemodynamic information to the clinicians would provide a useful analytical tool.
      A lumped parameters model of the circulation was applied to both beta-blocked and
      not beta-blocked pigs. The results confirmed a drop of cardiac output and
      coronary flow during heart lifting and a rise of both variables after the
      Trendelenburg maneuver for beta-blocked animals. In not beta-blocked pigs, the
      analysis was more complex but the model reproduced experimental data and
      permitted coronary flow to be estimated. These results showed the feasibility of
      numerical simulation for specific circulatory conditions encountered during
      beating-heart surgery.

PMID- 17209965
TI  - Strain hardening of red blood cells by accumulated cyclic supraphysiological
      stress.
AB  - The effect of elevated shear stress upon cellular trauma has been studied for
      many years, but the effect of long-term cyclic stress trauma on hemorheology has
      never been explored systematically. This study investigated sublytic trauma of
      red blood cells (RBCs) caused by repeated exposure to shear stress. A suspension
      of bovine blood was throttled through a capillary tube (inner diameter 1 mm and
      length 70 mm) connected to a recirculating flow loop. Samples were withdrawn
      every 30 min to measure deformability and characteristic time. The deformability
      of the cell was measured microscopically by observing the shape of the cell
      during the shear flow. It was found that cyclic shear irreversibly stiffened the
      cell membrane while the effect was not so much as that of continuous shear. The
      cell deformability was dramatically reduced by 73% when the stress of 300 Pa was
      applied for 288 s, while it was 7% under 90 Pa. These results elucidate the need
      for improved models to predict cellular trauma within the unsteady flow
      environment of mechanical circulatory assist devices.

PMID- 17209966
TI  - Lessons for neurology from paediatric oncology.

PMID- 17209968
TI  - Nature of motor imitation problems in school-aged males with autism.

PMID- 17209969
TI  - Nature of motor imitation problems in school-aged males with autism: how
      congruent are the error types?
AB  - This case-comparison study explores the underlying mechanisms of imitation
      problems in school-aged males with autism. Analysis of congruent error types in
      their imitation performance was made and compared with appropriate comparisons.
      Fifty-five males (eight low-functioning with autism: mean age 6y 2mo [SD 7.6mo];
      13 low-functioning with learning disabilities: mean age 6y 3mo [SD 2.8mo]; 17
      high-functioning with autism: mean age 8y 9mo [SD 11mo]; and 17 typically
      developing: mean age 8y 8mo [SD 11.6mo]) were assessed on 18 single gestures and
      six sequences of hand postures. Imitation performance was videotaped for blind
      scoring on 21 possible errors by two independent observers. Results revealed that
      in both groups with autism, imitation required far more effort (more attempts)
      than in the comparison groups and was less precise (more spatial errors). Typical
      for low-functioning participants with autism was their less mature imaginary grip
      in transitive gestures. Typical for high-functioning participants with autism was
      their preference for immature mirror-image imitations. These observations support
      the assumption that the underlying mechanisms in motor imitation problems are
      linked more to the action production system and less to the action conceptual
      system or to behavioural problems. We postulate that the action production system
      is delayed rather than deficient.

PMID- 17209970
TI  - Short-latency somatosensory evoked potentials in infantile autism: evidence of
      hyperactivity in the right primary somatosensory area.
AB  - Children with infantile autism sometimes show hyperesthesia or hypoesthesia to
      touch, pain, and/or temperature. To clarify the pathophysiology, we examined
      short-latency somatosensory evoked potentials (S-SEPs), elicited by median nerve
      stimulation, in 24 children with infantile autism (17 males, seven females; age
      range 2y 2mo-9y; mean age 4y 2mo [SD 1y 7mo]). We also evaluated relationships
      between S-SEP findings and clinical manifestations. Of the 24 children, 10 showed
      abnormal S-SEPs as follows: prolonged peak latency of N20 (n=2), extended
      interpeak latency of P13/14-N20 (n=7), appearance of a giant SEP (n=1), and a
      more than twofold right hemispheric peak-to-peak amplitude predominance of N20
      P25 (n=5). In addition, a peak-to-peak amplitude of N20-P25 elicited by left
      median nerve stimuli was significantly higher than that obtained with right
      median nerve stimuli, which indicated right hemispheric hyperactivity relative to
      the left (p=0.008). Infantile autism is frequently associated with somatosensory
      abnormalities and right hemispheric hyperactivity relative to the left,
      especially in the primary somatosensory area. This is believed to contribute to
      the pathophysiology of infantile autism, especially the idiopathic form.

PMID- 17209971
TI  - Orofacial dysfunction in children and adolescents with myotonic dystrophy.
AB  - Myotonic dystrophy (DM) is a neuromuscular disorder caused by an expansion of a
      CTG repeat sequence on chromosome 19q13. The aim of the present study was to
      describe the characteristics and prevalence of oral motor dysfunction in a cohort
      of children and adolescents with DM and to correlate different aspects of oral
      motor function with the type of DM and sex. Fifty-six individuals with DM (30
      males, 26 females; median age 13y 2mo; range 2y 6mo-21y 5mo) were compared with
      healthy controls. They were divided into four subgroups: severe congenital DM
      (n=18); mild congenital DM (n=18); childhood DM (n=18); and classical DM (n=2). A
      speech-language pathologist assessed different variables of oral motor function,
      intelligibility, and lip force. The families used a questionnaire to report on
      eating difficulties and drooling. All individuals with DM had impaired facial
      expression. Intelligibility was moderately or severely reduced in 30 patients
      (60%), excluding six patients without speech. Most had a moderate or severe
      impairment of lip motility (76.0%), tongue motility (52.2%), and lip force
      (69.2%), causing deviant production of bilabial and dental consonants. The
      families reported problems with eating (51.9%) and drooling (37.0%). Oral motor
      dysfunction was most prominent in congenital DM, and males were more affected
      than females.

PMID- 17209972
TI  - Modified constraint-induced movement therapy after childhood stroke.
AB  - The aim of this pilot study was to investigate feasibility, tolerability, and
      effect of modified constraint-induced movement therapy (mCIT) in children with
      hemiparesis after arterial ischaemic stroke (AIS). Children with chronic
      hemiparesis and impaired hand function after AIS had mCIT for 2 hours a day, 5
      days a week for 4 weeks. Pre- and post-therapy assessments included indices of
      sensorimotor function, quality of upper limb movement, functional therapy goals,
      and child and parent interviews. Of eight participants initially recruited, six
      (one male, five females) completed mCIT (median age 12y 3mo; range 6y 10mo-15y
      2mo). Hemiparesis was predominantly spastic in three participants and dystonic in
      the others; all had severely impaired hand function. After mCIT there were no
      significant improvements in sensorimotor function or quality of upper limb
      movement. However, all children improved in individual therapy goals related to
      functional performance. Children and parents were positive about mCIT. The use of
      mCIT is a promising intervention for children with chronic acquired hemiparesis.
      In this severely impaired group functional improvements were seen after therapy
      despite unchanged sensorimotor measures.

PMID- 17209973
TI  - Developmental delay and magnocellular visual pathway function in very-low
      birthweight preterm infants.
AB  - This study investigated the effect of very preterm birth (gestation < or =30wks)
      and very low birth weight (< or =1500g) on the development of magnocellular and
      parvocellular visual processing streams. Participants were preterm infants (n=55:
      31 females, 24 males) born between 24 and 30 weeks'gestation (mean 27.4wks [SD
      1.3]), weighing between 720 and 1470g (mean 1015g [SD 215]) and term infants
      (n=52: 27 females, 25 males) born between 38 and 42 weeks'gestation (mean 39.4wks
      [SD 0.9]), weighing between 2670 and 4405g (mean 3549g [SD 440]). Visual-evoked
      potentials to phase-reversing sine-wave gratings, varying in spatial frequency
      and contrast, were used to elicit magnocellular and parvocellular specific
      responses. Previous studies found that the N1 component reflects the
      parvocellular response, while P1 reflects the magnocellular response in adults
      and infants. Findings from the current study indicate significantly lower P1
      amplitudes in preterm compared with term infants under most conditions. No
      difference was found for the amplitude of the N1 waveform. Results indicate that,
      for the age-range tested, preterm birth has little effect on the development of
      parvocellular function, while it appears to disrupt the development of
      magnocelluar function.

PMID- 17209974
TI  - Ball catching in children with developmental coordination disorder: control of
      degrees of freedom.
AB  - This study investigated two-handed catching in eight children (four males, four
      females) aged 7 to 8 years (mean 7y 4mo [SD 3mo]) with developmental coordination
      disorder (DCD) and their age-matched controls (AMCs). Kinematic data were
      collected to examine Bernstein's (1967) notion of freezing and releasing degrees
      of freedom (DF). Participants were asked to catch a ball 30 times, delivered in
      three blocks of 10 trials. Video analysis showed that children with DCD caught
      significantly fewer balls than their AMCs (p< or =0.001) counterparts. Kinematic
      analyses showed that children with DCD exhibited smaller ranges of motion and
      less variable angular excursions of the elbow joints than their AMCs, and that
      their elbows are more rigidly coupled (p< or =0.001). These data suggest that
      children with DCD rigidly fix and couple their limbs to reduce the number of DF
      actively involved in the task.

PMID- 17209975
TI  - Ankle dorsiflexion fMRI in children with cerebral palsy undergoing intensive body
      weight-supported treadmill training: a pilot study.
AB  - This pilot study investigated the feasibility of using functional magnetic
      resonance imaging (fMRI) as a physiological marker of brain plasticity before and
      after an intensive body-weight-supported treadmill training (BWSTT) program in
      children with cerebral palsy (CP). Six ambulatory children (four males, two
      females; mean age 10y 6mo, age range 6-14y) with spastic CP (four hemiplegia, two
      asymmetric diplegia, all Gross Motor Function Classification System Level I)
      received BWSTT twice daily for 2 weeks. All children tolerated therapy; only one
      therapy session was aborted due to fatigue. With training, over ground mean
      walking speed increased from 1.47 to 1.66m/s (p=0.035). There was no change in
      distance walked for 6 minutes (pre-: 451m; post-: 458m;p 0.851). In three
      children, reliable fMRIs were taken of cortical activation pre- and post
      intervention. Post-intervention increases in cortical activation during ankle
      dorsiflexion were observed in all three children. This study demonstrates that
      children with CP between 6 and 14 years of age can tolerate intensive locomotor
      training and, with appropriate modifications, can complete an fMRI series. This
      study supports further studies designed to investigate training-dependent
      plasticity in children with CP.

PMID- 17209976
TI  - Reproducibility evaluation of gross and net walking efficiency in children with
      cerebral palsy.
AB  - In evaluating energy cost (EC) of walking, referred to as walking efficiency, the
      use of net measurement protocols (i.e. net=gross-resting) has recently been
      recommended. However, nothing is known about the comparative reproducibility of
      net protocols and the commonly used gross protocols. Ten minutes of resting and 5
      minutes of walking at a self-selected speed were used to determine gross and net
      EC in 13 children with spastic cerebral palsy (CP; seven males, six females; mean
      age 8y 7mo [SD 3y 4mo], range 4y 1mo-13y) and in 10 children (three males, seven
      females) with typical development. In the former, their Gross Motor Function
      Classification System levels ranged from Level I to Level III; and seven had
      hemiplegia and six diplegia. There were four repeated sessions on different days,
      with periods of 1 week between sessions. Reproducibility was assessed for speed,
      and gross and net EC, by using the standard error of measurement. The results of
      this preliminary study showed that EC measurements were more variable for
      children with CP than for children with typical development. Furthermore, in both
      groups there was considerably more variability in the net measurements than in
      the gross measurements. We conclude that, on the basis of the methodology used,
      the use of gross EC, rather than net EC, seems a more sensitive measure of
      walking efficiency to detect clinically relevant changes in an individual child
      with CP.

PMID- 17209977
TI  - Psychometric properties of the quality of life questionnaire for children with
      CP.
AB  - This paper describes the development and psychometric properties of a condition
      specific quality of life instrument for children with cerebral palsy (CP QOL
      Child). A sample of 205 primary caregivers of children with CP aged 4 to 12 years
      (mean 8y 5mo) and 53 children aged 9 to 12 years completed the CP QOL-Child. The
      children (112 males, 93 females) were sampled across Gross Motor Function
      Classification System (GMFCS) levels (Level I=18%, II=28%, III=14%, IV=11%,
      V=27%). Primary caregivers also completed other measures of child health (Child
      Health Questionnaire; CHQ), QOL (KIDSCREEN), and functioning (GMFCS). Internal
      consistency ranged from 0.74 to 0.92 for primary caregivers and from 0.80 to 0.90
      for child self-report. For primary caregivers, 2-week test-retest reliability
      ranged from 0.76 to 0.89. The validity of the CP QOL is supported by the pattern
      of correlations between CP QOL-Child scales with the CHQ, KIDSCREEN, and GMFCS.
      Preliminary statistics suggest that the child self-report questionnaire has
      acceptable psychometric properties. The questionnaire can be freely accessed at
      http://www.deakin.edu.ac/hmnbs/chase/cerebralpalsy/cp_qol_home.php.

PMID- 17209978
TI  - Motor function following multilevel botulinum toxin type A treatment in children
      with cerebral palsy.
AB  - This study evaluated the effects of multilevel botulinum toxin type A (BTX-A)
      treatments on the gait pattern of children with spastic cerebral palsy (Gross
      Motor Function Classification System Levels I-III). In this nested case-control
      design, 30 children (mean age 6y 11mo [SD 1y 5mo]; 21 males, nine females; 19
      with hemiplegia, 11 with diplegia) were treated according to best practice
      guidelines in paediatric orthopaedics, including BTX-A injections. A matched
      control group of 30 children (mean age 7y 8mo [SD 1y 10mo]; 13 males, 17 females;
      19 with hemiplegia, 11 with diplegia) were treated identically, but without BTX
      A. Motor development status at 5 to 10 years of age was assessed by means of
      three-dimensional gait analysis at a mean time of 1 year 10 months (SD 10mo)
      after the last BTX-A treatment. The control group showed a significantly more
      pronounced pathological gait pattern than the BTX-A group. Major differences were
      found for pelvic anterior tilt, maximum hip and knee extension, and internal hip
      rotation. These results provide evidence for a prolonged effect of BTX-A and
      suggest that BTX-A injections, in combination with common conservative treatment
      options, result in a gait pattern that is less defined by secondary problems
      (e.g. bony deformities) at 5 to 10 years of age, minimizing the need for complex
      surgery at a later age and enhancing quality of life.

PMID- 17209979
TI  - Secondary non-response due to antibody formation in a child after three
      injections of botulinum toxin B into the salivary glands.
AB  - Botulinum toxin (BTX) offers a new treatment option to reduce drooling in adults
      and children. Antibody formation against BTX is known to be one reason for
      clinical secondary non-response to this treatment. This is a case report on the
      development of secondary non-response to BTX type B (BTX-B) in a 15-year-old
      male, with bilateral dyskinetic cerebral palsy (Gross Motor Function
      Classification System Level IV) with additional learning disability* and
      microcephaly, treated for the indication of drooling. After three successful
      treatment sessions, the fourth and fifth injections showed no clinical response.
      This was associated with the presence of antibodies against BTX-B as determined
      using the mouse diaphragm assay. Thus, formation of neutralizing antibodies
      against BTX-B appears to be an important issue, not only in patients treated for
      cervical dystonia but also in children treated for drooling. Subsequent
      injections with an adequate dose of BTX type A (BTX-A) did not show any clinical
      response either, although no antibodies to BTX-A were detected. Besides the
      unanswered questions of dosing and distribution, a second possible explanation
      could be that BTX-B gave rise to non-neutralizing antibodies that cross-react
      with BTX-A. The resulting immune complexes could be taken up by phagocytes and,
      thereby, impede clinical response.

PMID- 17209980
TI  - A previously undescribed leukodystrophy in Leigh syndrome associated with T9176C
      mutation of the mitochondrial ATPase 6 gene.
AB  - We report two male Taiwanese siblings in whom the T-->C point mutation at
      nucleotide 9176 of the mitochondrial ATPase 6 gene (m.9176T>C mutation) was
      associated with early onset hypotonia, lactic acidosis, and death due to
      respiratory arrest at 7 and 10 months old. Brain MRI showed lesions over diffuse
      white matter and the bilateral posterior limbs of the internal capsule. The
      m.9176T>C mutation is suggested as the cause of the bilateral striatal necrosis
      and Leigh syndrome. However, leukodystrophy in Leigh syndrome associated with
      m.9176T>C mutation has never been reported before. We suggest that m.9176T>C
      mutation could be a new aetiology for leukodystrophy in children with Leigh
      syndrome.

PMID- 17209981
TI  - Does horseback riding therapy or therapist-directed hippotherapy rehabilitate
      children with cerebral palsy?
AB  - Quantitative (not qualitative) studies were sought investigating whether
      horseback riding used as therapy improves gross motor function in children with
      cerebral palsy (CP). Eleven published studies on instructor-directed,
      recreational horseback riding therapy (HBRT) and licensed-therapist-directed
      hippotherapy were identified, reviewed, and summarized for research design,
      methodological quality, therapy regimen, internal/external validity, results, and
      authors'conclusions. Methodological quality was moderate to good for all studies;
      some studies were limited by small sample size or lack of non-riding controls.
      HBRT improved gross motor function in five of six studies (one study was
      inconclusive); hippotherapy improved gross motor function in all five studies.
      The studies found that during HBRT and hippotherapy: (1) the three-dimensional,
      reciprocal movement of the walking horse produced normalized pelvic movement in
      the rider, closely resembling pelvic movement during ambulation in individuals
      without disability; (2) the sensation of smooth, rhythmical movements made by the
      horse improved co-contraction, joint stability, and weight shift, as well as
      postural and equilibrium responses; and (3) that HBRT and hippotherapy improved
      dynamic postural stabilization, recovery from perturbations, and anticipatory and
      feedback postural control. The evidence suggests that HBRT and hippotherapy are
      individually efficacious, and are both medically indicated as therapy for gross
      motor rehabilitation in children with CP. Recommendations for future research are
      discussed.

PMID- 17209982
TI  - 'Transient dystonic toe-walking: differentiation from cerebral palsy and a rare
      explanation for some unexplained cases of idiopathic toe-walking'.

PMID- 17209983
TI  - Sex and the pathogenesis of cerebral palsy.
AB  - Cerebral palsy (CP) and related developmental disorders are more common in males
      than in females, but the reasons for this disparity are uncertain. Males born
      very preterm also appear to be more vulnerable to white matter injury and
      intraventricular hemorrhage than females. Experimental studies in adult animals
      and data from adult patients with stroke indicate that sex hormones such as
      estrogens provide protection against hypoxic-ischemic injury, and the neonatal
      brain is also influenced by these hormones. However, hormonal influences on the
      fetus and neonates are substantially different from those on adults. Recent data
      from neonatal rodents subjected to hypoxia-ischemia also demonstrate differences
      between males and females. Knockout of the gene for poly (ADP-ribose) polymerase
      (PARP-1), a major step in the cascade of injury, protected male but not female
      mouse pups from hypoxic-ischemic injury. Other reports demonstrated major
      differences between male and female neurons grown separately in cell culture,
      suggesting that sex differences in the fetal or neonatal period result from
      intrinsic differences in cell death pathways. This new information indicates that
      there are important neurobiological differences between males and females with
      respect to their response to brain injuries. This information is relevant to
      understanding the pathogenesis of CP as well as to the design of future clinical
      trials of potential neuroprotective strategies.

PMID- 17209984
TI  - East European and Mediterranean meeting on cerebral palsy and developmental
      medicine, Warsaw, Poland, 8-10 june 2006.

PMID- 17209985
TI  - 'Influence of subclinical generalized spike-wave activity on the heart rate of
      children with epilepsy'.

PMID- 17209986
TI  - A tale of two matrices: multivariate approaches in evolutionary biology.
AB  - Two symmetric matrices underlie our understanding of microevolutionary change.
      The first is the matrix of nonlinear selection gradients (gamma) which describes
      the individual fitness surface. The second is the genetic variance-covariance
      matrix (G) that influences the multivariate response to selection. A common
      approach to the empirical analysis of these matrices is the element-by-element
      testing of significance, and subsequent biological interpretation of pattern
      based on these univariate and bivariate parameters. Here, I show why this
      approach is likely to misrepresent the genetic basis of quantitative traits, and
      the selection acting on them in many cases. Diagonalization of square matrices is
      a fundamental aspect of many of the multivariate statistical techniques used by
      biologists. Applying this, and other related approaches, to the analysis of the
      structure of gamma and G matrices, gives greater insight into the form and
      strength of nonlinear selection, and the availability of genetic variance for
      multiple traits.

PMID- 17209987
TI  - A cautionary tale of two matrices: the duality of multivariate abstraction.

PMID- 17209988
TI  - The dangers of diagonalization.

PMID- 17209989
TI  - A tale of two methods: putting biology before statistics in the study of
      phenotypic evolution.

PMID- 17209990
TI  - A fable of four functions.

PMID- 17209991
TI  - A dispatch from the multivariate frontier.

PMID- 17209992
TI  - The biology of multivariate evolution.

PMID- 17209993
TI  - The stability of genetic variance-covariance matrix in the presence of selection.

PMID- 17209994
TI  - A wake-up call for studies of natural selection?

PMID- 17209995
TI  - Multivariate selection for the rest of us.

PMID- 17209996
TI  - Escape from flatland.

PMID- 17209998
TI  - The genetic architecture of male colour differences between a sympatric Lake
      Malawi cichlid species pair.
AB  - The genetic basis of traits involved in reproductive isolation is a key parameter
      in models of sympatric speciation by sexual selection, a potential mechanism
      driving the explosive radiation of East African cichlids. Analysis of hybrid
      crosses between two sympatric Lake Malawi cichlid species, representing the
      extremes of the extant colour distribution, generated Castle-Wright estimates of
      four to seven loci controlling colour differences. Segregation patterns deviated
      from a purely additive model with a significant contribution from dominance, and
      possibly also epistasis. Evidence was found for a strong influence of autosomal
      loci. As departures from simple additive variation could effect the operation of
      models of sympatric speciation, dominance and epistasis should not be neglected.

PMID- 17209999
TI  - Dose-dependent schistosome-induced mortality and morbidity risk elevates host
      reproductive effort.
AB  - Parasitism changes the host environment and may influence resource allocation
      between reproductive effort and somatic maintenance. We characterized the impact
      of dose-dependent schistosome exposure and/or infection establishment on
      intermediate host survival and reproduction. Four matched groups of Biomphalaria
      glabrata snails were individually exposed to increasing doses of Schistosoma
      mansoni parasites, with a fifth control group remaining unexposed. Increased
      mortality was observed amongst both snails infected and also those snails exposed
      to the parasite but within which infection did not establish, although only
      exposed but uninfected snails showed a dose-dependent increase in mortality.
      Snails also facultatively altered their reproductive output in response to
      parasite exposure: egg mass production decreased with increasing parasite dose in
      patently infected snails, whilst, in contrast, exposed but uninfected snails
      demonstrated a positive association between egg mass production and parasite dose
      in the post-patent period. These results uniquely suggest an exposure-dose
      dependent post-patent fecundity compensation occurring in relation to the risk of
      future parasite-associated mortality.

PMID- 17210000
TI  - Host-plant effects the expression of resistance to Bacillus thuringiensis
      kurstaki in Trichoplusia ni (Hubner): an important factor in resistance
      evolution.
AB  - Pathogens are thought to exert strong selection on their hosts leading to
      increased host resistance. Bacillus thuringiensis kurstaki (Bkt) is a ubiquitous
      entomopathogen that has become the mainstay of nonchemical control of
      Lepidopteran pests and thus, the potential exists for the evolution of resistance
      in targeted host insects. We have studied the expression of Btk resistance in the
      cabbage looper, Trichoplusia ni (Hubner). For this generalist insect herbivore,
      three common host plants, tomato, pepper and cucumber, vary in suitability for
      larval growth and development. Here we show that the host plant also affects the
      overall toxicity of Btk, the relative expression of resistance between a
      resistant and a susceptible line and their F(1) reciprocal crosses, and
      importantly, the dominance of the resistance trait. This study demonstrates that
      tri-trophic interactions involving an insect, host plants and a pathogen have the
      potential to strongly influence the evolutionary response of an insect host to a
      pathogen.

PMID- 17210001
TI  - Feeding with speed: prey capture evolution in cichilds.
AB  - The diversity of both the locomotor and feeding systems in fish is extensive,
      although little is known about the integrated evolution of the two systems.
      Virtually, all fish swim to ingest prey and all open their buccal cavity during
      prey capture, but the relationship between these two ubiquitous components of
      fish feeding strikes is unknown. We predicted that there should be a positive
      correlation between ram speed (RS) and maximum gape (MG) because the accuracy of
      a predatory strike goes down with an increase in RS and fish with larger mouths
      eat larger, more evasive prey. For 18 species of neotropical cichlids, we used
      phylogenetic-independent contrasts to study the relationship between the predator
      closing speed (RS) and mouth size (MG) during prey capture. To provide a robust
      comparative framework, we augmented existing phylogenetic information available
      from the mitochondrial cytochrome b gene with sequences from the S7 nuclear
      ribosomal intron for these species. Then, we captured high-speed (500 images per
      second), lateral view feeding sequences of each species by using a digital video
      camera and measured both RS and MG. Uncorrected species values of MG and RS were
      positively and significantly correlated. When accounting for any of the set of
      phylogenetic relationships recovered, the independent contrasts of RS and MG
      remained significantly, and positively, correlated. This tight evolutionary
      coupling highlights what is likely a common relationship between locomotor
      behaviour and feeding kinematics in many organisms.

PMID- 17210002
TI  - Host inbreeding increases susceptibility to ectoparasitism.
AB  - Inbreeding, which increases homozygosity throughout the genome by increasing the
      proportion of alleles that are identical by descent, is expected to compromise
      resistance against parasitism. Here, we demonstrate that host inbreeding
      increases susceptibility to ectoparasitism in a natural fruit fly (Drosophila
      nigrospiracula) - mite (Macrocheles subbadius) association, and that this effect
      depends on host genetic background. Moreover, flies generated from reciprocal
      crosses between susceptible inbred lines exhibited elevated levels of resistance
      similar to that in the mass-bred base population, confirming in reverse direction
      the causative link between expected heterozygosity and resistance. We also show
      that inbreeding reduces the host's ability to sustain energetically expensive
      behaviours, and that host exhaustion dramatically increases susceptibility. These
      findings suggest that inbreeding depression for resistance results from an
      inability to sustain defensive behaviours because of compromised physiological
      competence.

PMID- 17210003
TI  - Correlated responses to artificial body size selection in growth, development,
      phenotypic plasticity and juvenile viability in yellow dung flies.
AB  - Most life history traits are positively influenced by body size, whereas
      disadvantages of large body size are poorly documented. To investigate presumed
      intrinsic costs of large size in the yellow dung fly (Scathophaga stercoraria;
      Diptera: Scathophagidae), we established two replicates each of three body size
      laboratory selection lines (small, control and large; selection on males only),
      and subjected flies of the resulting extended body size range to various abiotic
      stresses. Response to selection was symmetrical in the small and large lines
      (realized h(2) = 0.16-0.18). After 24 generations of selection body size had
      changed by roughly 10%. Female size showed a correlated response to selection on
      male size, whereas sexual size dimorphism did not change. Development time also
      showed a correlated response as, similar to food limited flies, small line flies
      emerged earlier at smaller body size. At the lowest larval food limit possible,
      flies of all lines emerged at the same small body size after roughly the same
      development time; so overall phenotypic plasticity in body size and development
      time strongly increased following selection. Juvenile mortality increased
      markedly when food was extremely limited, large line flies showing highest
      mortality. Winter frost disproportionately killed large (line) flies because of
      their longer development times. Mortality at high temperatures was high but size
      selective effects were inconsistent. In all environments the larger males
      suffered more. Initial growth rate was higher for males and at unlimited food.
      Small line individuals of both sexes grew slowest at unlimited larval food but
      fastest at limited larval food, suggesting a physiological cost of fast growth.
      Overall, extension of the natural body size range by artificial selection
      revealed some otherwise cryptic intrinsic juvenile viability costs of large size,
      mediated by longer development or faster growth, but only in stressful
      environments.

PMID- 17210004
TI  - The evolutionary history of the common chloroplast genome of Arabidopsis thaliana
      and A. suecica.
AB  - The evolutionary history of the common chloroplast (cp) genome of the
      allotetraploid Arabidopsis suecica and its maternal parent A. thaliana was
      investigated by sequencing 50 fragments of cpDNA, resulting in 98 polymorphic
      sites. The variation in the A. suecica sample was small, in contrast to that of
      the A. thaliana sample. The time to the most recent common ancestor (T(MRCA)) of
      the A. suecica cp genome alone was estimated to be about one 37th of the T(MRCA)
      of both the A. thaliana and A. suecica cp genomes. This corresponds to A. suecica
      having a MRCA between 10 000 and 50 000 years ago, suggesting that the entire
      species originated during, or before, this period of time, although the estimates
      are sensitive to assumptions made about population size and mutation rate. The
      data was also consistent with the hypothesis of A. suecica being of single
      origin. Isolation-by-distance and population structure in A. thaliana depended
      upon the geographical scale analysed; isolation-by-distance was found to be weak
      on the global scale but locally pronounced. Within the genealogical cp tree of A.
      thaliana, there were indications that the root of the A. suecica species is
      located among accessions of A. thaliana that come primarily from central Europe.
      Selective neutrality of the cp genome could not be rejected, despite the fact
      that it contains several completely linked protein-coding genes.

PMID- 17210005
TI  - Environment and pollinator-mediated selection on parapatric floral races of
      Mimulus aurantiacus.
AB  - We tested whether selection by pollinators could explain the parapatric
      distribution of coastal red- and inland yellow-flowered races of Mimulus
      aurantiacus (Phrymaceae) by examining visitation to natural and experimental
      populations. As a first step in evaluating whether indirect selection might
      explain floral divergence, we also tested for local adaptation in early life
      stages using a reciprocal transplant experiment. Hummingbirds visited flowers of
      each race at similar rates in natural populations but showed strong (>95%)
      preference for red flowers in all habitats in experimental arrays. Hawkmoths
      demonstrated nearly exclusive (>99% of visits) preference for yellow flowers and
      only visited in inland regions. Strong preferences for alternative floral forms
      support a direct role for pollinators in floral divergence. Despite these
      preferences, measures of plant performance across environments showed that red
      flowered plants consistently survived better, grew larger and received more
      overall pollinator visits than yellow-flowered plants. Unmeasured components of
      fitness may favour the yellow race in inland habitats. Alternatively, we document
      a marked recent increase in inland hummingbird density that may have caused a
      change in the selective environment, favouring the eastward advance of red
      flowered plants.

PMID- 17210006
TI  - Inheritance of progeny sex ratio in Urtica dioica.
AB  - Seed samples collected from female Urtica dioica plants in the field showed
      considerable inter-family variation in the sex ratio (faction of males). To
      investigate the inheritance pattern of the sex ratio trait, crosses were
      performed between individual male and female plants from different sex ratio
      families. Our results suggest, at least for the families studied here, that
      maternal parents strongly contribute to the variation in the primary sex ratio.
      Furthermore, progeny sex ratios from reciprocal crosses were significantly
      different and resembled the sex ratios produced by their maternal parents. We
      discuss the possible mechanisms underlying maternal control.

PMID- 17210007
TI  - Pupal period and adult size in Drosophila melanogaster: a cautionary tale of
      contrasting correlations between two sexually dimorphic traits.
AB  - Sexual dimorphism (SD) is widespread, reflecting a resolution of genetic
      conflicts arising from sex-specific differences in selection. However, genetic
      correlations among traits may constrain the evolution of SD. Drosophila
      melanogaster exhibits SD for pupal period (males longer) and adult weight
      (females heavier). This negative inter-sex covariance between the traits
      contrasts with a significant intra-sex positive genetic correlation (r(g) = 0.95)
      estimated using lines selected for fast larval development. Path analysis
      indicated that within sexes the selection regime indirectly reduced adult weight
      which in turn reduced pupal period. A hypothesis is proposed for the evolution of
      SD whereby the trait 'pupal period' is divided into 'intrinsic' (correlated with
      body size) and 'ecological' (uncorrelated with body size) components, and (the
      larger) females eclose earlier than males size via a shortening of the ecological
      component, thus achieving the advantage of provisioning eggs prior to sexual
      maturity. This hypothesis avoids invoking successful 'incompatible antagonistic
      selection'.

PMID- 17210008
TI  - Hybridization and reproductive isolation among syntopic populations of the
      topminnows Fundulus notatus and F. olivaceus.
AB  - Fundulus notatus and Fundulus olivaceus are two closely related topminnow species
      that exhibit similar ecological niches and broad, largely overlapping, North
      American ranges extending throughout much of the Mississippi River drainage as
      well as the coastal drainages of the Gulf of Mexico. Previous studies have
      suggested that these two species are reproductively compatible despite
      cytogenetic differences and will hybridize when syntopic. We used nuclear and
      mtDNA loci to assess levels of hybridization and test for introgression in
      syntopic populations of these two species in four drainages in southern Illinois.
      Although hybridization was detected in all syntopic populations, an assessment of
      the proportion of hybrid individuals indicated a deficiency of hybrids relative
      to expectations under random mating. We determined that, although mtDNA
      introgression was prevalent and extended beyond the zones of contact, evidence of
      nuclear introgression was limited to the zone of sympatry.

PMID- 17210009
TI  - Presence of soldier larvae determines the outcome of competition in a
      polyembryonic wasp.
AB  - Soldier-producing polyembryonic waSPS are the only social animals that develop as
      parasites inside the bodies of other insects. Characterizing the kin composition
      of broods is central to understanding the evolution of the soldier caste in these
      unique social insects. Here we studied the role of soldiers in mediating the
      outcome of competition among clones of the polyembryonic wasp Copidosoma
      floridanum. Soldier-producing female clones usually monopolized host resources,
      whereas soldierless male clones usually coexisted in hosts. Behavioural
      experiments further indicated that early-emerging soldiers are specialized to
      combat intraspecific competitors and later-emerging soldiers are specialized for
      defence against interspecific competitors. Taken together, our results point to
      intraspecific competition as a major selective force in the evolution of the
      soldier caste. Our data also present an evolutionary conundrum: given the benefit
      of soldiers, why are male clones functionally soldierless?

PMID- 17210010
TI  - Resolving the tragedy of the commons: the feedback between intraspecific conflict
      and population density.
AB  - Competition and conflict among individuals can favour exploitative strategies
      that undermine the common good. Theory suggests that this can lead to a tragedy
      of the commons and ultimately population extinction, a phenomenon known as
      evolutionary suicide. Here, I present a model of the evolutionary tragedy of the
      commons that explicitly considers the population dynamics where individuals
      invest in individually costly competitive traits. In the simplest form, this
      supports the notion that selection for high levels of conflict can cause
      evolutionary suicide. However, as competition comes with survival and fecundity
      costs, a feedback between the investment in competition and population density
      can act to reduce the level of conflict and prevent the population from going
      extinct. This suggests that the interaction between population ecology and the
      evolution of competition and conflict among individuals may be an important
      mechanism in resolving the level of competition and conflict among individuals.

PMID- 17210011
TI  - The evolution of trans-generational altruism: kin selection meets niche
      construction.
AB  - A cornerstone result of sociobiology states that limited dispersal can induce kin
      competition to offset the kin selected benefits of altruism. Several mechanisms
      have been proposed to circumvent this dilemma but all assume that actors and
      recipients of altruism interact during the same time period. Here, this
      assumption is relaxed and a model is developed where individuals express an
      altruistic act, which results in posthumously helping relatives living in the
      future. The analysis of this model suggests that kin selected benefits can then
      feedback on the evolution of the trait in a way that promotes altruistic helping
      at high rates under limited dispersal. The decoupling of kin competition and kin
      selected benefits results from the fact that by helping relatives living in the
      future, an actor is helping individuals that are not in direct competition with
      itself. A direct consequence is that behaviours which actors gain by reducing the
      common good of present and future generations can be opposed by kin selection.
      The present model integrates niche-constructing traits with kin selection theory
      and delineates demographic and ecological conditions under which altruism can be
      selected for; and conditions where the 'tragedy of the commons' can be reduced.

PMID- 17210012
TI  - Genotype-by-environment interactions leads to variable selection on life-history
      strategy in Common Evening Primrose (Oenothera biennis).
AB  - Monocarpic plant species, where reproduction is fatal, frequently exhibit
      variation in the length of their prereproductive period prior to flowering. If
      this life-history variation in flowering strategy has a genetic basis, genotype
      by-environment interactions (G x E) may maintain phenotypic diversity in
      flowering strategy. The native monocarpic plant Common Evening Primrose
      (Oenothera biennis L., Onagraceae) exhibits phenotypic variation for annual vs.
      biennial flowering strategies. I tested whether there was a genetic basis to
      variation in flowering strategy in O. biennis, and whether environmental
      variation causes G x E that imposes variable selection on flowering strategy. In
      a field experiment, I randomized more than 900 plants from 14 clonal families
      (genotypes) into five distinct habitats that represented a natural productivity
      gradient. G x E strongly affected the lifetime fruit production of O. biennis,
      with the rank-order in relative fitness of genotypes changing substantially
      between habitats. I detected genetic variation in annual vs. biennial strategies
      in most habitats, as well as a G x E effect on flowering strategy. This variation
      in flowering strategy was correlated with genetic variation in relative fitness,
      and phenotypic and genotypic selection analyses revealed that environmental
      variation resulted in variable directional selection on annual vs. biennial
      strategies. Specifically, a biennial strategy was favoured in moderately
      productive environments, whereas an annual strategy was favoured in low
      productivity environments. These results highlight the importance of variable
      selection for the maintenance of genetic variation in the life-history strategy
      of a monocarpic plant.

PMID- 17210013
TI  - When bigger is not better: selection against large size, high condition and fast
      growth in juvenile lemon sharks.
AB  - Selection acting on large marine vertebrates may be qualitatively different from
      that acting on terrestrial or freshwater organisms, but logistical constraints
      have thus far precluded selection estimates for the former. We overcame these
      constraints by exhaustively sampling and repeatedly recapturing individuals in
      six cohorts of juvenile lemon sharks (450 age-0 and 255 age-1 fish) at an
      enclosed nursery site (Bimini, Bahamas). Data on individual size, condition
      factor, growth rate and inter-annual survival were used to test the 'bigger is
      better', 'fatter is better' and 'faster is better' hypotheses of life-history
      theory. For age-0 sharks, selection on all measured traits was weak, and
      generally acted against large size and high condition. For age-1 sharks,
      selection was much stronger, and consistently acted against large size and fast
      growth. These results suggest that selective pressures at Bimini may be
      constraining the evolution of large size and fast growth, an observation that
      fits well with the observed small size and low growth rate of juveniles at this
      site. Our results support those of some other recent studies in suggesting that
      bigger/fatter/faster is not always better, and may often be worse.

PMID- 17210014
TI  - Sex ratio variance and the maintenance of environmental sex determination.
AB  - Although variation in population sex ratios is predicted to increase the
      extinction rate of clades with environmental sex determination (ESD), ESD is
      still seen in a wide array of natural systems. It is unclear how this common sex
      determining system has persisted despite this inherent disadvantage associated
      with ESD. We use simulation modelling to examine the effect of the sex ratio
      variance caused by ESD on population colonization and establishment. We find that
      an accelerating function of establishment success on initial population sex ratio
      favours a system that produces variance in sex ratios over one that consistently
      produces even sex ratios. This sex ratio variance causes ESD to be favoured over
      genetic sex determination, even when the mean global sex ratio under both sex
      determining systems is the same. Data from ESD populations suggest that the
      increase in population establishment can more than offset the increased risk of
      extinction associated with temporal fluctuations in the sex ratio. These findings
      demonstrate that selection in natural systems can favour increased variance in a
      trait, irrespective of the mean trait value. Our results indicate that sex ratio
      variation may provide an advantage to species with ESD, and may help explain the
      widespread existence of this sex-determining system.

PMID- 17210015
TI  - Colour variation and alternative reproductive strategies in females of the common
      lizard Lacerta vivipara.
AB  - Within-sex colour variation is a widespread phenomenon in animals that often
      plays a role in social selection. In males, colour variation is typically
      associated with the existence of alternative reproductive strategies. Despite
      ecological conditions theoretically favourable to the emergence of such
      alternative strategies in females, the social significance of colour variation in
      females has less commonly been addressed, relative to the attention given to male
      strategies. In a population of the common lizard, females display three classes
      of ventral colouration: pale yellow, orange and mixed. These ventral colours are
      stable through individual's life and maternally heritable. Females of different
      ventral colourations displayed different responses of clutch size, clutch
      hatching success and clutch sex-ratio to several individual and environmental
      parameters. Such reaction patterns might reflect alternative reproductive
      strategies in females. Spatial heterogeneity and presence of density- and
      frequency-dependent feedbacks in the environment could allow for the emergence of
      such alternative strategies in this population and the maintenance of colour
      variation in females.

PMID- 17210016
TI  - Changed environmental conditions weaken sexual selection in sticklebacks.
AB  - Environmental heterogeneity can cause the intensity and direction of selection to
      vary in time and space. Yet, the effects of human-induced environmental changes
      on sexual selection and the expression of mating traits of native species are
      poorly known. Currently, the breeding habitats of the three-spined stickleback
      Gasterosteus aculeatus are changing in the Baltic Sea because of eutrophication
      and increased growth of algae. Here we show that enhanced growth of filamentous
      algae increases the costs of mating by inducing an increase in the time and
      energy spent on courtship and mate choice. This is not followed by a concomitant
      increase in mate attraction, but instead the strength of selection on male red
      nuptial coloration and courtship activity is relaxed. Thus, the high investment
      into the costly sexually selected traits is maladaptive under the new conditions,
      and the mating system mediates a negative effect of the environmental change on
      the population. We attribute these environmentally induced changes in the benefit
      of the mating traits and in the strength of sexual selection to reduced
      visibility in dense vegetation. Anthropogenic disturbances hence affect the
      selection pressures that mould the species, which could have long-term effects on
      the viability and evolution of the populations.

PMID- 17210017
TI  - Male mating preferences pre-date the origin of a female trait polymorphism in an
      incipient species complex of Lake Victoria cichlids.
AB  - Disruptive sexual selection on colour patterns has been suggested as a major
      cause of diversification in the cichlid species flock of Lake Victoria. In
      Neochromis omnicaeruleus, a colour and sex determination polymorphism is
      associated with a polymorphism in male and female mating preferences. Theoretical
      work on this incipient species complex found conditions for rapid sympatric
      speciation by selection on sex determination and sexual selection on male and
      female colour patterns, under restrictive assumptions. Here we test the
      biological plausibility of a key assumption of such models, namely, the existence
      of a male preference against a novel female colour morph before its appearance in
      the population. We show that most males in a population that lacks the colour
      polymorphism exhibit a strong mating preference against the novel female colour
      morph and that reinforcement is not a likely explanation for the origin of such
      male preferences. Our results show that a specific condition required for the
      combined action of selection on sex determination and sexual selection to drive
      sympatric speciation is biologically justified. Finally, we suggest that Lake
      Victoria cichlids might share an ancestral female recognition scheme,
      predisposing colour monomorphic populations/species to similar evolutionary
      pathways leading to divergence of colour morphs in sympatry.

PMID- 17210018
TI  - Effects of B chromosomes and supernumerary segments on morphometric traits and
      adult fitness components in the grasshopper, Dichroplus elongatus (Acrididae).
AB  - The South American species, Dichroplus elongatus, is polymorphic for B
      chromosomes and supernumerary segments in chromosome pairs M6 (SS6), S9 (SS9) and
      S10 (SS10). Both forms of supernumerary heterochromatin shape chiasma frequency
      and distribution and B chromosomes also affect male fertility. Here, we analysed
      the effects of these polymorphisms on morphometric traits (total, 3rd femur, 3rd
      tibia, thorax and tegmen lengths) and several adult fitness components, including
      male and female mating success, and female reproductive potential. B chromosomes
      tend to decrease, and SS6 segments to increase the body size of carriers. The
      analysis of reproductive potential suggested that B chromosome carrying females
      have higher numbers of embryos per clutch and ovarioles per ovary. The uni- and
      multivariate analysis of mating success revealed that sexual selection favours
      larger individuals of both sexes and males with standard karyotype. B chromosomes
      may have accumulation mechanisms, which involve preferential transmission of B
      chromosomes to germ cells or functional gametes. The maintenance of Bs might be
      explained by interactions among accumulation mechanisms and trade-offs between
      detrimental and favourable effects on different fitness components.

PMID- 17210019
TI  - The unusual inheritance pattern of the courtship songs in closely related
      grasshopper species of the Chorthippus albomarginatus-group (Orthoptera:
      Gomphocerinae).
AB  - Sibling species of the Chorthippus albomarginatus-group are exceptional among all
      European grasshopper species because they have an extremely elaborate courtship
      behaviour. Here, we present a genetic analysis of the courtship song differences
      between two closely related grasshopper species Ch. albomarginatus and Ch.
      oschei. Measurements of seven courtship song characters and one parameter of
      courtship visual display were compared among parentals, F(1) and F(2) hybrids,
      and backcrosses. Variation in one morphological character, the number of
      stridulatory pegs, was studied as well. The distributions of song phenotypes were
      more consistent with a type-III genetic architecture, which involves
      complementary or duplicate pairs of loci. We suggest that this type of
      architecture may provide the novel elements of the hybrid songs, even more
      complex than the parental ones, which may offer a new starting point for sexual
      selection. One parameter of the visual display appeared to be controlled by a
      single locus, but differences in other characters of visual display could be
      explained by a more complex inheritance pattern. Inheritance of the peg number
      differences was consistent with a simple polygenic additive model. Sex linkage
      and/or maternal effects were not detected for any trait. We found a
      disproportionate influence of the Ch. albomarginatus parent on most hybrid song
      characteristics and the visual display, and this may support a previously
      suggested idea that Ch. albomarginatus is an ancestral form and Ch. oschei is a
      derived species.

PMID- 17210020
TI  - Reinforcement of mate preference among hybridizing Heliconius butterflies.
AB  - Recent models of mate preference evolution suggest that direct selection on
      alleles at preference loci and correlated evolution of preference with locally
      adapted mating cues are more likely to drive the evolution of assortative mate
      preference than reinforcement. Mate preference evolution in mimetic Heliconius
      butterflies has been attributed to all three forms of selection, but here we show
      that reinforcement has been critical. By examining geographical variation in
      assortative mating and male mate preference among seven populations of three
      hybridizing Heliconius species from Costa Rica, we found pronounced character
      displacement of preference such that sexual isolation was enhanced in areas of
      interspecific contact. Of the different explanations for the evolution of
      assortative mate preference, only reinforcement is dependent on interspecific
      contact in this system. Thus, the observed pattern of reproductive character
      displacement of mate preference is best explained as a product of indirect
      selection generated by natural selection against nonmimetic hybrids.

PMID- 17210021
TI  - Dynamics of the evolution of Batesian mimicry: molecular phylogenetic analysis of
      ant-mimicking Myrmarachne (Araneae: Salticidae) species and their ant models.
AB  - Batesian mimicry is seen as an example of evolution by natural selection, with
      predation as the main driving force. The mimic is under selective pressure to
      resemble its model, whereas it is disadvantageous for the model to be associated
      with the palatable mimic. In consequence one might expect there to be an
      evolutionary arms race, similar to the one involving host-parasite coevolution.
      In this study, the evolutionary dynamics of a Batesian mimicry system of model
      ants and ant-mimicking salticids is investigated by comparing the phylogenies of
      the two groups. Although Batesian mimics are expected to coevolve with their
      models, we found the phylogenetic patterns of the models and the mimics to be
      indicative of adaptive radiation by the mimic rather than co-speciation between
      the mimic and the model. This shows that there is strong selection pressure on
      Myrmarachne, leading to a high degree of polymorphism. There is also evidence of
      sympatric speciation in Myrmarachne, the reproductive isolation possibly driven
      by female mate choice in polymorphic species.

PMID- 17210022
TI  - Experimental adaptation to high and low quality environments under different
      scales of temporal variation.
AB  - We investigated the role of the scale of temporal variation in the evolution of
      generalism in populations of the bacterium Pseudomonas fluorescens. Replicate
      populations were propagated as batch cultures for approximately 1400 generations
      (192 days), in either high quality media only, low quality media only, or were
      alternated between the two at a range of temporal scales (between 1 and 48 days).
      Populations evolved in alternating media showed fitness increases in both media
      and the rate of alternation during selection had no effect on average fitness in
      either media. Moreover, the fitness of these populations in high quality media
      was the same as for populations evolved only in high quality media and likewise
      for low quality media. Populations evolved only in high or low quality media did
      not show fitness improvements in their nonselective media. These results indicate
      that cost-free generalists can evolve under a wide range of temporal variation.

PMID- 17210023
TI  - Direct fitness or inclusive fitness: how shall we model kin selection?
AB  - Two standard mathematical formulations of kin-selection models can be found.
      Inclusive fitness is an actor-centred approach, which calculates the fitness
      effect on a number of recipients of the behaviour of a single actor. Direct
      fitness is a recipient-centred approach, which calculates the fitness effect on
      the recipient of the behaviour of a number of actors. Inclusive fitness offers us
      a powerful heuristic, of choosing behaviour to maximize fitness, but direct
      fitness can be mathematically easier to work with and has recently emerged as the
      preferred approach of theoreticians. In this paper, we explore the fundamental
      connection between these two approaches in both homogeneous and class-structured
      populations, and we show that under simple assumptions (mainly fair meiosis and
      weak selection) they provide equivalent formulations, which correspond to the
      predictions of Price's equation for allele frequency change. We use a couple of
      examples to highlight differences in their conception and formulation, and we
      briefly discuss a two-species example in which we have a class of 'actor' that is
      never a 'recipient', which the standard direct fitness method can handle but the
      usual inclusive fitness cannot.

PMID- 17210024
TI  - Carotenoid and protein supplementation have differential effects on pheasant
      ornamentation and immunity.
AB  - A currently popular hypothesis states that the expression of carotenoid-dependent
      sexual ornaments and immune function may be correlated because both traits are
      positively affected by carotenoids. However, such a correlation may arise for
      another reason: it is well known that immune function is dependent on nutritional
      condition. A recent study has suggested that the expression of ornaments may too
      depend on nutritional condition, as males in good nutritional condition are
      better at assimilating and/or modulating carotenoids. Thus, carotenoid-dependent
      ornaments and immune function may be correlated because both are dependent on
      nutritional condition. To elucidate if, and how, ornamentation and immune
      function are linked, pheasant diets were supplemented with carotenoid and/or
      protein in a fully factorial experiment. Carotenoid treatment affected wattle
      coloration and tail growth, but not cellular or humoral immunity. Immunity was
      unrelated to males' initial ornamentation including wattle colour. Males in
      better body condition, measured as residual mass, increased their wattle
      coloration more when carotenoid supplemented. Protein positively affected humoral
      but not cellular immunity, but had no effect on ornaments. Cellular, but not
      humoral, immunity increased with male body condition. Thus, there was no evidence
      that an immune-stimulatory effect of carotenoids resulted in wattle coloration
      honestly signalling immune function, but wattle coloration may still signal male
      body condition.

PMID- 17210025
TI  - Avian growth and development rates and age-specific mortality: the roles of nest
      predation and adult mortality.
AB  - Previous studies have shown that avian growth and development covary with
      juvenile mortality. Juveniles of birds under strong nest predation pressure grow
      rapidly, have short incubation and nestling periods, and leave the nest at low
      body mass. Life-history theory predicts that parental investment increases with
      adult mortality rate. Thus, developmental traits that depend on the parental
      effort exerted (pre- and postnatal growth rate) should scale positively with
      adult mortality, in contrast to those that do not have a direct relationship with
      parental investment (timing of developmental events, e.g. nest leaving). I tested
      this prediction on a sample of 84 North American songbirds. Nestling growth rate
      scaled positively and incubation period duration negatively with annual adult
      mortality rates even when controlled for nest predation and other covariates,
      including phylogeny. On the contrary, neither the duration of the nestling period
      nor body mass at fledging showed any relationship. Proximate mechanisms
      generating the relationship of pre- and postnatal growth rates to adult mortality
      may include increased feeding, nest attentiveness during incubation and/or
      allocation of hormones, and deserve further attention.

PMID- 17210026
TI  - An analysis of pre- and post-hatching maternal effects mediated by carotenoids in
      the blue tit.
AB  - Maternal effects increase phenotypic plasticity in offspring traits and may
      therefore facilitate adaptation to environmental variability. Carotenoids have
      been hypothesized to mediate costs of reproduction in females as well as maternal
      effects. However, assessing potential transgenerational and population
      consequences of environmental availability of carotenoids requires a better
      understanding of mechanisms of maternal effects mediated by these antioxidant
      pigments. Manipulating dietary availability of carotenoids to egg-laying female
      blue tits and subsequently cross-fostering nestlings between female treatments
      allowed us to specifically investigate the relative importance of maternal
      effects through egg carotenoids and through post-hatching care mediated by
      antioxidants in females. Nestling body size and mass and plasma antioxidants were
      not significantly affected by pre- or post-hatching maternal effects mediated by
      antioxidants, although both types of maternal effects in interaction explained
      the variation in growth, as measured by wing length. Development of the ability
      to mount a cell-mediated immune response as well as its temporal dynamics was
      influenced by both pre- and post-hatching maternal effects, with an advantage to
      nestlings originating from, or reared by, carotenoid-supplemented females. In
      addition, nestlings reared by carotenoid-fed females had a lower blood
      sedimentation rate, indicating that they may have been less infected than
      nestlings from controls. Finally, prehatching maternal effects in interaction
      with nestling plasma carotenoid levels affected the development of carotenoid
      based plumage. Maternal effects mediated by carotenoids may thus act as a
      proximate factor in development and phenotypic plasticity in traits associated
      with nestling fitness, such as immune response and ability to metabolize and use
      antioxidants, and ultimately participate in the evolution of phenotypic traits.

PMID- 17210027
TI  - Complementary sex determination in the parasitoid wasp Cotesia vestalis (C.
      plutellae).
AB  - In the Hymenoptera, single locus complementary sex determination (sl-CSD)
      describes a system where males develop either from unfertilized haploid eggs or
      from fertilized diploid eggs that are homozygous at a single polymorphic sex
      locus. Diploid males are often inviable or sterile, and are produced more
      frequently under inbreeding. Within families where sl-CSD has been demonstrated,
      we predict that sl-CSD should be more likely in species with solitary development
      than in species where siblings develop gregariously (and likely inbreed). We
      examine this prediction in the parasitoid wasp genus Cotesia, which contains both
      solitary and gregarious species. Previous studies have shown that sl-CSD is
      absent in two gregarious species of Cotesia, but present in one gregarious
      species. Here, we demonstrate CSD in the solitary Cotesia vestalis, using
      microsatellite markers. Diploid sons are produced by inbred, but not outbred,
      females. However, frequencies of diploid males were lower than expected under sl
      CSD, suggesting that CSD in C. vestalis involves more than one locus.

PMID- 17210028
TI  - Long day plants and the response to global warming: rapid evolutionary change in
      day length sensitivity is possible in wild beet.
AB  - Day length is a key factor in flowering induction in many plant species in a
      seasonal environment with flowering induction usually happening at shorter day
      lengths in lower latitudes. Now, the climate changes systematically at a
      considerable speed due to global warming. As a consequence, earlier flowering
      will be selected for in long day plants by favouring a lower threshold for day
      length sensitivity, on the condition of available genetic variability. Here, we
      show that there is considerable genetic variation for day length sensitivity in
      our study species, the seabeet Beta vulgaris subsp. maritima. In the northernmost
      natural populations without vernalization requirement, in southwest France, the
      necessary day length for flowering induction could be reduced by artificial
      selection in <10 generations from >13 h to <11 h, the latter value corresponding
      to populations in the Beta-species complex from Northern Africa and the eastern
      part of the Mediterranean tested under the same conditions. A quantitative
      genetic analysis provided evidence of a gradual change without detectable major
      genes. Additional experiments were carried out to separate the response to
      photoperiod from age and energy effects. A certain effect of energy availability
      has been found, whereas age effects could be excluded. These results indicate a
      considerable potential for evolutionary change in adjusting flowering time in a
      changing climate.

PMID- 17210029
TI  - Effects of cytoplasmic genes on sperm viability and sperm morphology in a seed
      beetle: implications for sperm competition theory?
AB  - Sperm competition theory predicts that sperm traits influencing male fertilizing
      ability will evolve adaptively. However, it has been suggested that some sperm
      traits may be at least partly encoded by mitochondrial genes. If true, this may
      constrain the adaptive evolution of such traits because mitochondrial DNA (mtDNA)
      is maternally inherited and there is thus no selection on mtDNA in males.
      Phenotypic variation in such traits may nevertheless be high because mutations in
      mtDNA that have deleterious effects on male traits, but neutral or beneficial
      effects in females, may be maintained by random processes or selection in
      females. We used backcrossing to create introgression lines of seed beetles
      (Callosobruchus maculatus), carrying orthogonal combinations of distinct lineages
      of cytoplasmic and nuclear genes, and then assayed sperm viability and sperm
      length in all lines. We found sizeable cytoplasmic effects on both sperm traits
      and our analyses also suggested that the cytoplasmic effects varied across
      nuclear genetic backgrounds. We discuss some potential implications of these
      findings for sperm competition theory.

PMID- 17210030
TI  - Recent invasion of the mountain birch Betula pubescens ssp. tortuosa above the
      treeline due to climate change: genetic and ecological study in northern Sweden.
AB  - Mountain birch, Betula pubescens ssp. tortuosa, forms the treeline in northern
      Sweden. A recent shift in the range of the species associated with an elevation
      of the treeline is commonly attributed to climate warming. Using microsatellite
      markers, we explored the genetic structure of populations along an altitudinal
      gradient close to the treeline. Low genetic differentiation was found between
      populations, whereas high genetic diversity was maintained within populations.
      High level of gene flow compensated for possible losses of genetic diversity at
      higher elevations and dissipated the founding effect of newly established
      populations above the treeline. Spatial autocorrelation analysis showed low
      spatial genetic structure within populations because of extensive gene flow. At
      the treeline, significant genetic structure within the juvenile age class at
      small distances did not persist in the adult age class, indicating recent
      expansion of young recruits due to the warming of the climate. Finally, seedling
      performance above the treeline was positively correlated with parameters related
      to temperature. These data confirm the high migration potential of the species in
      response to fluctuating environmental conditions and indicate that it is now
      invading higher altitudes due to the recent warming of the climate.

PMID- 17210031
TI  - Influence of developmental environment on male- and female-mediated sperm
      precedence in Drosophila melanogaster.
AB  - Length of the sperm flagellum and of the female's primary sperm-storage organ,
      the seminal receptacle (SR), exhibit a pattern of rapid correlated evolution in
      Drosophila and other lineages. Experimental evolution studies with Drosophila
      melanogaster indicate that these traits have coevolved through sexual selection,
      with length of the SR representing the proximal basis of female sire
      discrimination, biasing paternity according to sperm length. Here, we examine the
      impact of experimentally varying the developmental environment, including larval
      density and larval and adult nutrition, on sperm length, SR length and on the
      pattern of sperm precedence. Expression of SR length was far more sensitive to
      variation among developmental environments than was sperm length. Nevertheless,
      there was striking co-variation in sperm and SR length. The developmental
      environment of both females and second males, but not first males, significantly
      contributed to variation in male competitive fertilization success.

PMID- 17210032
TI  - High genetic divergences indicate ancient separation of parthenogenetic lineages
      of the oribatid mite Platynothrus peltifer (Acari, Oribatida).
AB  - Theories on the evolution and maintenance of sex are challenged by the existence
      of ancient parthenogenetic lineages such as bdelloid rotifers and darwinulid
      ostracods. It has been proposed that several parthenogenetic and speciose taxa of
      oribatid mites (Acari) also have an ancient origin. We used nucleotide sequences
      of the mitochondrial gene cytochrome oxidase I to estimate the age of the
      parthenogenetic oribatid mite species Platynothrus peltifer. Sixty-five specimens
      from 16 sites in North America, Europe and Asia were analysed. Seven major clades
      were identified. Within-clade genetic distances were below 2 % similar to the
      total intraspecific genetic diversity of most organisms. However, distances
      between clades averaged 56 % with a maximum of 125 %. We conclude that P.
      peltifer, as it is currently conceived, has existed for perhaps 100 million
      years, has an extant distribution that results from continental drift rather than
      dispersal and was subject to several cryptic speciations.

PMID- 17210033
TI  - Adaptive radiation in African weakly electric fish (Teleostei: Mormyridae:
      Campylomormyrus): a combined molecular and morphological approach.
AB  - We combined multiple molecular markers and geometric morphometrics to revise the
      current taxonomy and to build a phylogenetic hypothesis for the African weakly
      electric fish genus Campylomormyrus. Genetic data (2039 bp DNA sequence of
      mitochondrial cytochrome b and nuclear S7 genes) on 106 specimens support the
      existence of at least six species occurring in sympatry. We were able to further
      confirm these species by microsatellite analysis at 16 unlinked nuclear loci and
      landmark-based morphometrics. We assigned them to nominal taxa by comparisons to
      type specimens of all Campylomormyrus species recognized so far. Additionally, we
      showed that the shape of the elongated trunk-like snout is the major source of
      morphological differentiation among them. This finding suggests that the
      radiation of this speciose genus might have been driven by adaptation to
      different food sources.

PMID- 17210034
TI  - Reinventing the weal?

PMID- 17210035
TI  - Adenosine receptors: novel targets for drug development in allergic rhinitis.

PMID- 17210036
TI  - Targeting adenosine receptors in the treatment of allergic rhinitis: a
      randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND: There is evidence that adenosine plays a role in the pathogenesis of
      asthma and rhinitis; however, it is currently unclear whether adenosine receptors
      are useful therapeutic targets in the treatment of allergic airway diseases.
      OBJECTIVE: The study evaluated the efficacy of intranasal treatment with an
      adenosine A(2A) receptor agonist/adenosine A(3) receptor antagonist (50 micro g),
      administered twice daily for 7 days, to reduce nasal symptoms and release of
      inflammatory mediators following intranasal allergen challenge in patients with
      allergic rhinitis (AR). The compound was compared with twice-daily treatment with
      intranasal fluticasone proprionate nasal spray (FPANS) for 7 days. METHODS: A
      randomized, double-blind, double-dummy, placebo-controlled, three-way balanced,
      incomplete block, crossover study was conducted on 48 males with verified AR.
      Following intranasal challenge with either an extract from the house dust mite
      (HDM), Dermatophagoides pteronyssinus, rye grass or cat dander, nasal responses
      and the concentrations of albumin, tryptase, myeloperoxidase, eosinophilic
      cationic protein, epithelial neutrophil-activating protein-78 (ENA-78), IL-5 and
      IL-8 in nasal secretions were measured and treatment groups were compared.
      RESULTS: Drug improved nasal blockage but had no significant effect on
      rhinorrhoea, number of sneezes or peak nasal inspiratory flow measurements when
      compared with placebo. Drug reduced tryptase release after EAR but did not
      significantly reduce the levels of other mediators. CONCLUSION: A novel
      agonist/antagonist of adenosine A(2A) and A(3) receptors appears to have limited
      clinical benefit in both the early-phase and the late-phase response to
      intranasal allergen challenge. However, reduction of some pro-inflammatory
      mediators suggests that comparable, more selective compounds may have additional
      benefits meriting further investigation.

PMID- 17210037
TI  - Bronchial responsiveness to methacholine and adenosine 5'-monophosphate in atopic
      and non-atopic preschool children with recurrent wheezing.
AB  - BACKGROUND: It is well known that atopy is a major determinant of bronchial hyper
      responsiveness (BHR) in both asymptomatic and asthmatic children. However, the
      relationship between atopy and BHR has not been well studied in preschool
      children with wheezing. BHR is usually measured by bronchial challenges using
      direct and indirect stimuli. OBJECTIVE: The aim of this study was to investigate
      whether atopic and non-atopic preschool wheezers display similar or different BHR
      profiles for direct and indirect stimuli. METHODS: Methacholine and adenosine 5'
      monophosphate (AMP) bronchial challenges were performed in 4 to 6-year-old
      children with recurrent wheezing, using a modified auscultation method. The end
      point was defined as the appearance of wheezing and/or oxygen desaturation. Atopy
      was determined to be present when a child had at least one positive reaction to a
      panel of 13 common airborne allergens in the presence of positive and negative
      controls. RESULTS: A positive response to methacholine (an end-point
      concentration < or =8 mg/mL) was observed in 89.3% (50/56) of atopic wheezers and
      in 83.8% (31/37) of non-atopic wheezers (P=0.44) for the difference. By contrast,
      the frequency of a positive response to AMP (an end-point concentration < or =200
      mg/mL) was significantly higher in the atopic group (47/56, 83.9%) compared with
      the non-atopic group (12/37, 32.4%; P<0.01). CONCLUSION: While a majority of both
      atopic and non-atopic preschool wheezers were hyper-responsive to methacholine,
      atopic subjects were more hyper-responsive to AMP than non-atopic subjects. These
      findings suggest that atopic and non-atopic wheeze in preschool children are
      related to distinctive pathophysiologic pathways.

PMID- 17210038
TI  - Response to mannitol in asymptomatic subjects with airway hyper-responsiveness to
      methacholine.
AB  - BACKGROUND: Bronchial provocation using methacholine, a cholinergic agonist,
      causes airway narrowing directly by contraction of bronchial smooth muscle. While
      methacholine has a high sensitivity for identifying airway hyper-responsiveness
      (AHR), it does not have a high specificity to diagnose asthma and false-positive
      responses may be observed in non-asthmatics. Mannitol is an osmotic stimulus that
      acts indirectly to cause airway narrowing by release of endogenous
      bronchoconstricting mediators. OBJECTIVES: We tested the hypothesis that subjects
      with asymptomatic AHR to methacholine would not have AHR to mannitol. METHODS:
      Sixteen subjects with a methacholine PD(20) <8 micro mol were challenged with
      mannitol. A positive response to mannitol was defined as a 15% decline in forced
      expiratory volume in 1 s (FEV(1)) after <635 mg (PD(15)). Expired nitric oxide
      (eNO) and blood eosinophils were also measured. RESULTS: The GM PD(20) for
      methacholine was 2.25 micro mol [95% confidence interval (CI): 2.19-5.29], the
      mean eNO was 14.7 p.p.b. (CI: 10.1-19.4) and the eosinophil count was 0.20 x 10(
      9)/L (CI: 0.14-0.27 x 10(-9)/L). Only one subject (a smoker, 10 pack-years,
      FEV(1) 76% pred, non-allergic rhinitis, normal eNO and eosinophil count) also had
      a mild positive response to mannitol (PD(15): 451 mg). CONCLUSIONS: The response
      to mannitol was within the normal range in asymptomatic subjects with AHR to
      methacholine. Further evidence on the responsiveness to mannitol compared with
      methacholine in a random population sample is required to elucidate whether
      mannitol is a more specific test for diagnosing asthma.

PMID- 17210039
TI  - Ectopic lung transplantation induces the accumulation of eosinophil progenitors
      in the recipients' lungs through an allergen- and interleukin-5-dependent
      mechanism.
AB  - BACKGROUND: Airway challenge of ovalbumin-sensitized mice induces intrapulmonary
      accumulation of eosinophil progenitors. OBJECTIVE: To evaluate whether allergen
      challenged lungs release factors promoting intrapulmonary accumulation of
      haemopoietic cells, and define the role of allergic lung injury, we developed a
      transplantation model. METHODS: Lung tissue from allergen-challenged, sensitized
      donors was ectopically grafted in syngeneic recipients, and haemopoietic
      progenitors inside the lungs of the recipients were quantified. RESULTS: In
      BALB/c mice, accumulation of progenitors occurred only when: (a) donors were
      sensitized and airway challenged with homologous allergen; (b) and recipients
      were sensitized. Grafts from the appropriate donors released biologically active
      IL-5, which was effective in sensitized recipients. The effect of the appropriate
      donor-recipient combination was prevented by neutralizing anti-IL-5 antibody.
      Grafts from unchallenged, sensitized donors synergized with recombinant IL-5 in
      sensitized recipients. Unlike BALB/c, grafts from naive IL-5 transgenic CBA/Ca
      mice (whose lungs contained a large number of progenitors, independently of
      sensitization and challenge) were effective in non-transgenic, ovalbumin
      sensitized recipients. CONCLUSION: This shows that: (a) intrapulmonary
      accumulation of progenitors is independent of immunological injury; (b) grafts
      systemically release IL-5, which is required for progenitor accumulation in the
      recipients' lungs; (c) and sensitization is required for full responsiveness to
      IL-5 and for generation of lung-derived signals that synergize with IL-5.

PMID- 17210040
TI  - Reaction pattern to histamine and codeine in a human intradermal skin test model.
AB  - BACKGROUND: Skin prick and intradermal skin tests (IDT) are useful tools in
      evaluating IgE-mediated allergic disorders. In the literature, many variations of
      the techniques used are described. No general agreement exists on test procedures
      and reading of test results. OBJECTIVE: To analyse test conditions for IDT to
      facilitate comparability between different study protocols. METHODS: We tested 24
      healthy volunteers with three concentrations of histamine and codeine each on the
      upper back, lateral upper arm and volar forearm, with/without addition of
      ethylene diamine tetra-acetic acid. Reading of the resulting weal was performed
      by taking a digital image of the weal, later outlining the weal perimeter in
      triplicate and calculating the weal area using the NIH Image J software version
      1.3. RESULTS: Weal size was dose dependent for both substances, generally larger
      on the upper back than on the forearm and upper arm, and larger after codeine
      than after histamine. Addition of the Ca2+ -chelator ethylene diamine tetra
      acetic acid did not significantly affect weal size. Weal size induced by
      histamine showed better consistency than that induced by codeine. CONCLUSIONS:
      The results and our technique provide valuable tools for the daily routine as
      well as for the ability to compare information of intradermal tests from
      different studies or clinical reports. When assessing skin reactivity, we
      recommend the use of 1 mg/mL codeine as well as 0.1 mg/mL histamine to reflect
      aspects of mast-cell releasability and of vascular reactivity. The involvement of
      local factors influencing the vascular reactivity or differences in opiate
      receptor density on mast cells surfaces needs to be addressed in future studies.

PMID- 17210041
TI  - Asthma in young south Asian women living in the United Kingdom: the importance of
      early life.
AB  - BACKGROUND: Studies of immigrants suggest that the environment during fetal life
      and duration of residence in the host country might influence the development of
      asthma. Little is known about the importance of the timing of the exposure in the
      host country and whether migrants might be especially vulnerable in certain age
      windows. OBJECTIVE: We compared the reported prevalence of asthma between young
      white and south Asian women in the United Kingdom, and investigated associations
      with country of birth and age at immigration. METHODS: A questionnaire on atopic
      disorders was posted to 2380 south Asian and 5796 white young mothers randomly
      sampled in Leicestershire. Data on ethnicity were also available from maternity
      records. Data were analysed using multivariable logistic regression and a
      propensity score approach. Results The reported prevalence of asthma was 10.9% in
      south Asian and 21.8% in white women. South Asian women who migrated to the
      United Kingdom aged 5 years or older reported less asthma (6.5%) than those born
      in the United Kingdom or who migrated before age 5 (16.0%), with an adjusted odds
      ratio of 0.38 [95% Confidence Interval 0.23-0.64, P<0.001]. For those who
      migrated aged over 5 years, the prevalence did not alter with the duration of
      residence in the United Kingdom. Current exposure to common environmental risk
      factors had relatively little effect on prevalence estimates. CONCLUSION: These
      data from a large population-based study support the hypothesis that early life
      environmental factors influence the risk of adult asthma.

PMID- 17210042
TI  - Retinol concentrations after birth are inversely associated with atopic
      manifestations in children and young adults.
AB  - BACKGROUND: Vitamin A has anti-inflammatory and immunomodulatory effects, and its
      deficiency results in impaired specific and innate immunity. Vitamin A is
      essential for inducing the gut-homing specificity on T cells. OBJECTIVE: As an
      impaired gut immune response in early infancy may contribute to the development
      of atopic sensitization, we looked for an association of plasma retinol
      concentrations and the subsequent development of allergic symptoms in healthy
      infants. METHODS: A cohort of 200 unselected, full-term newborns were followed up
      from birth to age 20 years. The plasma retinol concentration was determined in
      cord blood (n=97), at ages of 2, 4 and 12 months (n=95), and at ages 5 years
      (n=155) and 11 years (n=151). The subjects were re-examined at the ages of 5, 11
      and 20 years with assessment of the occurrence of allergic symptoms during the
      preceding year, skin prick testing and measurement of serum total IgE. RESULTS:
      subjects with allergic symptoms or a positive skin prick test (SPT) in childhood
      or adolescence had lower retinol concentrations in infancy and childhood than
      symptom-free subjects. The difference was most pronounced at age 2 months.
      Retinol concentration at 2 months correlated inversely with positive SPT at ages
      of 5 and 20 years, and with allergic symptoms at age 20 years. CONCLUSION:
      Retinol concentration in young infants is inversely associated with the
      subsequent development of allergic symptoms. We propose that an inborn regulation
      of retinol may play a role in atopic sensitization, possibly through regulating
      the intestinal T cell responses.

PMID- 17210043
TI  - Increased levels of circulating soluble CD14 but not CD83 in infants are
      associated with early intestinal colonization with Staphylococcus aureus.
AB  - BACKGROUND: Soluble forms of the monocyte marker CD14 and the mature dendritic
      cell marker CD83 are plasma proteins with immunoregulatory functions. The
      physiological stimulus for their production is unclear and their possible role in
      allergy development is unknown. METHODS: We measured the plasma levels of soluble
      CD14 (sCD14) and soluble CD83 (sCD83) in 64 Swedish children in relation to
      intestinal bacterial colonization pattern in a prospective birth cohort. Soluble
      CD14 and sCD83 levels were quantified by enzyme linked immunosorbent assay in
      plasma obtained at birth and at 4, 18 and 36 months of age. All major aerobic and
      anaerobic bacteria were quantified in faecal samples obtained regularly over the
      first 8 weeks of life. Clinical allergy and IgE levels were evaluated at 18
      months of age. RESULTS: Soluble CD14 in plasma increased during the first 18
      months of life while sCD83 peaked at 4 months of age. Children who were
      perinatally colonized with Staphylococcus aureus had significantly higher levels
      of sCD14 in plasma at 4 months of age relative to non-colonized children. The
      levels of sCD14 were unrelated to colonization with Escherichia coli, other
      enterobacteria, enterococci, clostridia, Bacteroides, bifidobacteria or
      lactobacilli. Further, children with food allergy by 18 months tended to have
      lower levels of sCD14 than healthy children. Plasma levels of sCD83 were not
      related to either bacterial colonization pattern or allergy development.
      CONCLUSIONS: Perinatal colonization with S. aureus may trigger the occurrence of
      sCD14 in plasma, which may influence development of the infantile immune system
      and risk of allergy development.

PMID- 17210044
TI  - Inhaled allergen-driven CD1c up-regulation and enhanced antigen uptake by
      activated human respiratory-tract dendritic cells in atopic asthma.
AB  - BACKGROUND: Dendritic cells (DC) mediate inflammation in rodent models of
      allergic airway disease, but the role played by human respiratory-tract DC
      (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1
      antigen presentation by hRTDC may contribute to asthma pathogenesis. OBJECTIVE:
      To investigate the influence of hRTDC on the balance between atopy and allergic
      asthma in human subjects and to determine whether CD1 expression by hRTDC is
      modulated during asthmatic inflammation. METHODS: Sputum cells were induced from
      steroid-naive, allergen-challenged and allergen-naive subjects (atopic
      asthmatics, atopic non-asthmatics and non-atopic controls). hRTDC were identified
      using monoclonal antibody labelling and analysis by flow cytometry. RESULTS:
      hRTDC stained HLA-DR(+) (negative for markers of other cell lineages) were
      predominantly myeloid and comprised approximately 0.5% of viable sputum cells.
      Sputum cells were potent stimulators of allogeneic CD4(+) naive T cells and
      enrichment/depletion experiments correlated stimulatory potency with DC numbers.
      Sputum contained cells that exhibited typical dendritic morphology when analysed
      by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of
      FITC-dextran was enhanced in cells from asthmatics (P<0.001). Despite their
      increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and
      expressed increased levels of maturation markers (P<0.05-P<0.001), CD1c, CD1d and
      langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon
      in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c(
      )CD123(high) hRTDC were only detected in asthmatic sputum and were increased in
      number following allergen challenge. CONCLUSION: Despite limited cell numbers, it
      proved possible to analyse human RTDC in induced sputum, providing evidence that
      increased antigen uptake and enhanced CD1 presentation by activated hRTDC may
      contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma
      may therefore constitute a novel target for future intervention strategies.

PMID- 17210045
TI  - Chromosome 7p linkage and GPR154 gene association in Italian families with
      allergic asthma.
AB  - BACKGROUND: Several genome scans have reported linkage of markers on chromosome
      7p with asthma and related phenotypes in different populations. A fine mapping in
      Finnish and French-Canadian populations has associated the GPR154 gene (also
      known as G-protein-coupled receptor for asthma susceptibility, GPRA) with
      elevated IgE or asthma. OBJECTIVE: To confirm chromosome 7p linkage and candidate
      gene association in Italian families with atopic asthma. METHODS: In a two-phase
      approach, we first performed a linkage analysis of chromosome 7, and then a
      family-based association study on the GPR154 gene for allergic asthma phenotypes
      in the Italian population. RESULTS: The screening of 117 families with 19
      microsatellite markers showed potential linkage for elevated IgE (P<0.002 at 22
      cM from p-ter), asthma (P<0.005 at 44 cM), or atopy (P<0.005 at 54 cM). In the
      second phase of the present study, candidate gene GPR154, which is located in the
      phase one-linked region, was investigated in 211 families with seven single
      nucleotide polymorphisms (SNPs) that tag most haplotype variability, by the
      pedigree disequilibrium test. Elevated IgE levels were associated with two GPR154
      gene SNPs (SNP 546333, P=0.0046; rs740 347, P=0.006), and with haplotypes in the
      global test (P=0.013). Haplotype analysis performed in nuclear families having at
      least 1 asthmatic parent showed a significant association with asthma (P=0.0173),
      atopy (P=0.0058), SPT (P=0.0025), and bronchial hyper reactivity (P=0.0163).
      CONCLUSION: These results support a susceptibility locus for asthma and related
      phenotypes on chromosome 7, and are in agreement with recent reports suggesting
      that a common susceptibility factor for atopic manifestations in asthma is likely
      conferred by the locus containing the GPR154 gene.

PMID- 17210046
TI  - Standardized training for healthcare professionals and its impact on patients
      with perennial rhinitis: a multi-centre randomized controlled trial.
AB  - BACKGROUND: Perennial rhinitis is common and often results in substantial,
      potentially avoidable, impairment of quality of life. Quality of rhinitis care
      has been shown to be sub-optimal in general practice. Rigorous evaluation of
      educational interventions for healthcare professionals using randomized
      controlled trials is very uncommon. OBJECTIVE: To evaluate the effectiveness of
      standardized allergy training for healthcare professionals on patients' disease
      specific quality of life. METHODS: Patients with clinician diagnosed perennial
      rhinitis and/or a prescription for relevant nasal medication were recruited from
      general practice. Following baseline measurement of quality of life using the
      validated rhino-conjunctivitis questionnaire (RQLQ), patients were centrally
      randomized to receive care from an allergy-trained primary healthcare
      professional or routine care. RQLQ was measured again at 13 months after
      randomization. RESULTS: Process measures revealed that the training was well
      received. 202 patients were included in the intention-to-treat analysis and 157
      in the per-protocol analysis. There was a 0.23 greater mean improvement in
      quality-of-life scores in the intervention group when compared with controls
      (P=0.08) in the intention-to-treat analysis, this increasing to a 0.3 greater
      mean improvement if confined to a per-protocol analysis (P=0.05). The intention
      to-treat analysis showed that 39/101 (39%) in the intervention group showed a
      clinically significant > or =0.5 improvement in RQLQ compared with 28/101 (28%)
      of controls (risk difference=11%, number needed to treat=9, P=0.1). CONCLUSIONS:
      Standardized allergy education given to primary healthcare professionals leads to
      modest improvements in disease-specific quality of life in patients with
      perennial rhinitis.

PMID- 17210047
TI  - Validated safety predictions of airway responses to house dust mite in asthma.
AB  - BACKGROUND: House dust mite (HDM) is the most common aeroallergen causing
      sensitization in many Western countries and is often used in allergen inhalation
      challenges. The concentration of inhaled allergen causing an early asthmatic
      reaction [provocative concentration of inhaled allergen causing a 20% fall of
      forced expiratory volume in 1 s (FEV(1))(PC(20) allergen)] needs to be predicted
      for safety reasons to estimate accurately the severity of allergen-induced airway
      responsiveness. This can be accomplished by using the degree of non-specific
      airway responsiveness and skin sensitivity to allergen. OBJECTIVE: We derived
      prediction equations for HDM challenges using PC(20) histamine or PC(20)
      methacholine and skin sensitivity data obtained from patients with mild to
      moderate persistent asthma and validated these equations in an independent asthma
      population. METHODS: PC(20) histamine or PC(20) methacholine, skin sensitivity,
      and PC(20) allergen were collected retrospectively from 159 asthmatic patients
      participating in allergen challenge trials. Both the histamine and methacholine
      groups (n=75 and n=84, respectively), were divided randomly into a reference
      group to derive new equations to predict PC(20) allergen, and a validation group
      to test the new equations. RESULTS: Multiple linear regression analysis revealed
      that PC(20) allergen could be predicted either from PC(20) methacholine only
      ((10)log PC(20) allergen=-0.902+0.741.(10)log PC(20) methacholine) or from PC(20)
      histamine and skin sensitivity (SS) ((10)log PC(20) allergen=-0.494+0.231.(10)log
      SS+0.546.(10)log PC(20) histamine). In the validation study, these new equations
      accurately predicted PC(20) allergen following inhalation of HDM allergen
      allowing a safe starting concentration of allergen of three doubling
      concentrations below predicted PC(20) allergen in all cases. CONCLUSION: The
      early asthmatic response to inhaled HDM extract is predominantly determined by
      non-specific airway responsiveness to methacholine or histamine, whereas the
      influence of the cutaneous sensitivity to HDM appears to be rather limited. Our
      new equations accurately predict PC(20) allergen and hence are suitable for
      implementation in HDM inhalation studies.

PMID- 17210048
TI  - Does skin prick test reactivity to purified allergens correlate with clinical
      severity of peanut allergy?
AB  - BACKGROUND: Recognition of specific peanut allergens or the diversity of IgE
      binding to peanut allergens may play a role in the elicitation of severe allergic
      reactions. OBJECTIVE: To investigate whether sensitization to individual
      allergens Ara h 1, Ara h 2, Ara h 3 and Ara h 6 is correlated with clinical
      severity. METHODS: The reactivity of purified peanut allergens was measured by
      skin prick test (SPT) and by IgE immunoblot in 30 patients. The results were
      related to the clinical reactivity by history, and in 25 of them to the eliciting
      dose (ED). RESULTS: The majority of patients recognized Ara h 2 and Ara h 6.
      Patients with severe symptoms had a higher SPT response to Ara h 2 and Ara h 6 at
      low concentrations (0.1 micro g/mL) and to Ara h 1 and Ara h 3 at higher
      concentrations (100 micro g/mL), compared with patients with mild symptoms. They
      also recognized a greater number of allergens and showed a higher cumulative SPT
      response compared with patients with mild symptoms. No significant differences
      were observed between patients with a low or high ED. CONCLUSIONS: Ara h 2 and
      Ara h 6 appeared to be more potent than Ara h 1 and Ara h 3. Both SPT reactivity
      to low concentrations of Ara h 2 and Ara h 6 and to higher concentrations of Ara
      h 1 and Ara h 3 were shown to be indicative of severe symptoms.

PMID- 17210049
TI  - Detection of an allergen in dog dander that cross-reacts with the major cat
      allergen, Fel d 1.
AB  - BACKGROUND: A considerable proportion of animal-allergic patients are sensitized
      to both cat and dog allergens but knowledge about cross-reactive allergens in cat
      and dog dander is limited. OBJECTIVE: To investigate whether dog dander contains
      an allergen that cross-reacts with the major cat allergen, Fel d 1. METHODS:
      Recombinant Fel d 1 with the same immunological properties as natural Fel d 1 was
      used for quantitative (CAP) IgE competition experiments performed with sera
      obtained from cat-allergic patients (n=36). A Fel d 1 cross-reactive dog allergen
      was characterized by one- and two-dimensional immunoblotting using rFel d 1 for
      IgE inhibition experiments and with monospecific, polyclonal rabbit anti
      recombinant Fel d 1 antibodies. RESULTS: In 25% of Fel d 1-reactive cat-allergic
      patients, more than 50% inhibition of IgE reactivity to dog allergens was
      achieved with recombinant Fel d 1. An Fel d 1 cross-reactive 20 kDa allergen with
      a pI of approximately 3.4 was detected in dander extracts of several different
      dog breeds. CONCLUSION: This is the first report demonstrating the presence of an
      Fel d 1-like allergen in dog dander extracts, which may be responsible for double
      positivity to cat and dog in serology. However, the clinical relevance of this
      cross-sensitization needs to be confirmed. These results are important for the
      diagnostic and therapeutic use of dog dander allergen extracts.

PMID- 17210050
TI  - Detection of airborne allergen (Ole e 1) in relation to Olea europaea pollen in S
      Spain.
AB  - BACKGROUND: In recent years, it has been demonstrated that the air carries not
      only airborne pollen but also plant particles of smaller size that have
      allergenic activity, and, being within the respirable range, these particles can
      trigger rapid attacks in the lower respiratory tract. The study of particles
      according to size (0.7-40 micro m) could provide valuable information on the real
      allergenic activity in the atmosphere. OBJECTIVE: The purpose of this study was
      to analyse the dynamics of airborne Olea europaea pollen in contrast to the
      allergenic activity of Ole e 1 in the atmosphere. METHODS: The analyses were
      carried out with a Hirst-type volumetric collector and a cascade impactor
      simultaneously during the MPS of the olive. The indirect ELISA was used to detect
      the allergenic activity. The sampling was performed in Granada city centre (S
      Spain), in the Science Faculty building on the University of Granada from 30
      April to 26 June 2005. RESULTS AND CONCLUSIONS: This research demonstrates that
      both the allergenic activity as well as the pollen particles follow in a similar
      curve, except in periods before or succeeding the main Olea pollen season. The
      study of the distribution of the allergenic particles according to their sizes
      reveals that the highest concentrations are between 3.3 and <0.7 micro m, thus
      indicating that allergenic activity primarily involves paucimicronic particles.

PMID- 17210051
TI  - Hev b 6.01 and Hev b 5 induce pro-inflammatory cytokines and chemokines from
      peripheral blood mononuclear cells in latex allergy.
AB  - BACKGROUND: Hev b 6.01 (prohevein) and Hev b 5 [acidic natural rubber latex (NRL)
      protein] are major IgE-binding allergens in NRL allergy. OBJECTIVE: To examine
      allergen-specific cytokine and chemokine responses in NRL-allergic patients.
      METHODS: Fourteen NRL-allergic patients and 10 healthy controls participated in
      the study. Hev b 6.01 and Hev b 5 were purified under non-denaturating conditions
      by chromatographic methods. Specific IgE antibodies were measured by ELISA and
      proliferation of peripheral blood mononuclear cells (PBMC) by (3)H-thymidine
      incorporation assay. Allergen-specific induction of cytokine and chemokine mRNA
      in PBMC was measured by real-time PCR and protein levels by ELISA. Surface
      expression of chemokine receptors was analysed by flow cytometry. RESULTS: Twelve
      (86%) NRL-allergic patients had positive skin prick test reactions and IgE
      antibodies against Hev b 6.01, but less than 30% responded to Hev b 5. Cell
      proliferation against Hev b 6.01, but not against Hev b 5, was significantly
      increased. Both allergens elicited significantly higher expression of pro
      inflammatory and T-helper type 2 cytokines (TNF, IL-12p40, IL-13) and chemokines
      (CCL3, CCL4, CCL20) in the NRL-allergic patients than in controls. Interestingly,
      mRNA expression of the regulatory cytokine TGF-beta1 was reduced, whereas IL-10
      expression was enhanced after allergen stimulations in patients with NRL allergy.
      Finally, the NRL-allergic patients showed increased CCR4 expression on CD3(+)CD8(
      ) T cells and decreased CXCR3 expression on CD3(+)CD8(+) T cells. CONCLUSION:
      Allergen-specific induction of cytokines and chemokines in PBMC and chemokine
      receptor expression on circulating T cells may contribute to the pathogenesis of
      NRL allergy.

PMID- 17210052
TI  - Mediator release assays based on human or murine immunoglobulin E in allergen
      standardization.
AB  - BACKGROUND: The biological potency of allergens can be measured by provoking
      mediator release from effector cells. As established immunochemical methods in
      allergen standardization only determine inhibition potency or major allergen
      content, routine tests for biological potency may enhance standardization and
      batch control of allergen products. OBJECTIVE: The general performance and
      application potential of biological in vitro assays in batch control and
      standardization of allergens and as a tool for verifying activity and stability
      of allergen standards were analysed. METHODS: Allergen extracts of five
      clinically relevant allergens from three to five different manufacturers were
      investigated. A CAP-IgE-inhibition assay was compared with mediator release assay
      (MRA)s based on murine or human basophils. Rat basophilic leukaemia (RBL) cells
      were passively sensitized with pooled murine allergen-specific IgE-containing
      sera. Humanized RBL cells and human-stripped basophils were sensitized with
      pooled patient's sera, which were also used for the CAP-IgE-inhibition assay.
      Allergen specificity of the sera was determined by immunoblotting. RESULTS: A
      good batch-to-batch consistency was found with each assay among all manufacturers
      and allergens tested. Between different manufacturers, the products showed
      differences in activity and the various assays indicated an almost identical
      ranking. However, the biological assays revealed qualitative differences of
      biological activity or composition of allergen preparations undetectable by IgE
      inhibition assay. CONCLUSIONS: MRAs provide refined information on allergen
      activity, either confirming the results of IgE-inhibition assay, or indicating
      differences requiring further investigation, and represent a highly sensitive
      novel tool in allergen standardization. By using permanently cultivated cell
      lines, repeated venepuncture to obtain human basophils is avoided. As in the RBL
      assay, the coefficient of variation for the release values were below 15% and for
      the ED50 below 25%, the assay is suitable to determine differences that are
      relevant for batch control purposes.

PMID- 17210053
TI  - Repeated epicutaneous exposures to ovalbumin progressively induce atopic
      dermatitis-like skin lesions in mice.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic skin disease in which
      environmental factors play a great role. A widely used murine model for AD has
      provided a useful tool to study the disease. OBJECTIVE: The purpose of this study
      is to investigate kinetically the induction of this AD model and the processes
      involved in the development of AD due to extrinsic allergen exposures. METHODS:
      BALB/c mice were epicutaneously exposed to ovalbumin (OVA) for 3 weeks; each week
      was separated by a 2-week resting period. Mice were killed after each exposure
      week. Skin biopsies and blood were obtained for histological study, RNA isolation
      and antibody analysis. RESULTS: There was a progressive and significant
      thickening of the epidermis and dermis in OVA-exposed mice. Significantly
      increased dermal cell infiltration of eosinophils, mast cells and total
      inflammatory cells, including CD3 and CD4 cells, was found after each OVA
      exposure week. Total IgE, IgG2a and OVA-specific IgE were significantly increased
      after the second and third exposure week, while OVA-specific IgG2a was
      significantly induced after the third exposure week. Gradual and/or significant
      increases in mRNA expression of IL-1beta, TNF-alpha, IL-4, IL-10, IL-13, IFN
      gamma and IL-12p35 were found after each exposure week. Chemokines and their
      receptors involved in both T-helper type 1 (Th1)- and Th2-type cell recruitment
      (CCL1, CCL8, CCL11, CCL24, CXCL9, CXCL10, CCR1, CCR3, CCR5, CCR8 and CXCR3) were
      up-regulated significantly at different time-points. CONCLUSION: This study
      provides an insight into the dynamic nature and time-dependent transition of skin
      inflammation and systemic immune responses in a murine AD model induced by
      repeated epicutaneous exposures to OVA.

PMID- 17210054
TI  - A guided tour into subcellular colocalization analysis in light microscopy.
AB  - It is generally accepted that the functional compartmentalization of eukaryotic
      cells is reflected by the differential occurrence of proteins in their
      compartments. The location and physiological function of a protein are closely
      related; local information of a protein is thus crucial to understanding its role
      in biological processes. The visualization of proteins residing on intracellular
      structures by fluorescence microscopy has become a routine approach in cell
      biology and is increasingly used to assess their colocalization with well
      characterized markers. However, image-analysis methods for colocalization studies
      are a field of contention and enigma. We have therefore undertaken to review the
      most currently used colocalization analysis methods, introducing the basic
      optical concepts important for image acquisition and subsequent analysis. We
      provide a summary of practical tips for image acquisition and treatment that
      should precede proper colocalization analysis. Furthermore, we discuss the
      application and feasibility of colocalization tools for various biological
      colocalization situations and discuss their respective strengths and weaknesses.
      We have created a novel toolbox for subcellular colocalization analysis under
      ImageJ, named JACoP, that integrates current global statistic methods and a novel
      object-based approach.

PMID- 17210055
TI  - Stoichiometry and valence measurements of niobium oxides using electron energy
      loss spectroscopy.
AB  - Qualitative and quantitative electron energy-loss spectroscopy analyses have been
      performed on niobium and stable niobium oxides (NbO, NbO(2) and Nb(2)O(5)). At
      integration windows (Delta) greater than 75 eV, k-factor analysis can be used to
      distinguish between the stoichiometry of the three oxides within 5.7% error. As
      seen in other metal oxides, with increasing oxidation state the metal ionization
      edges shift to higher energies relative to the O-K edge. Normalized M(2,3) white
      line intensities show a strong correlation with 4d occupancy for each compound.
      The data are in correspondence with that observed in the literature for 4d
      transition metals using normalized L(2,3) white lines. Lastly, a distinctive
      energy-loss near-edge, structure of the O-K edge was observed for each oxide,
      which could be used as a fingerprint for analysis of unknowns.

PMID- 17210056
TI  - Guided-wave and ellipsometric imaging of supported cells.
AB  - In this study, results are reported from guided-wave microscopy and imaging
      ellipsometry near the angle of resonant excitation of an optical guided mode in
      planar wave guides with metal and dielectric layers. The main goal was to test
      their ability to detect micro-organisms (Escherichia coli) attached to a support.
      For this purpose, images from the two techniques were compared with an optical
      image and good agreement was found. The reasons for the differences between the
      pictures obtained with wave-guide microscopy and imaging ellipsometry were
      investigated and it was found that both the reduced plasmon propagation length
      and the use of additional polarizing elements contributed to the improved quality
      of the latter.

PMID- 17210057
TI  - Optimized temporal response in multichannel two-photon fluorescence lifetime
      microscopy using a photonic crystal fibre.
AB  - The integration of fibre optics into an imaging system for the convenient
      delivery and collection of light has resulted in many hybrid forms of novel
      biomedical optical instrumentation. Although it is extremely robust and cost
      effective, fibre integration requires special consideration in a time-domain
      fluorescence lifetime imaging schema where multipath propagation in the fibre
      causes significant spread in photon transit times. In this study, we investigated
      the effect of the length of a multimode collection fibre on the temporal
      performance of a multichannel fluorescence lifetime microscope and demonstrated
      the effectiveness of a photonic crystal fibre as a means of optimizing the
      collection and delivery of emitted fluorescence in terms of temporal resolution.
      The findings are pertinent to all studies that employ a multimode optical fibre
      to collect and deliver an emitted fluorescence signal from a sample to a remote
      detector for measurement of the characteristic fluorescence lifetime.

PMID- 17210058
TI  - Electron backscatter diffraction on pearlite structures in steel.
AB  - Electron backscatter diffraction measurements were performed on a set of
      pearlitic steel samples after different heat treatments. The strengths and
      limitations of the technique with respect to the pearlite issue are presented.
      Interpretation of the obtained results confirmed that more than one pearlite
      colony may exist inside one ferrite nodule of nearly the same crystallographic
      orientation. It was also found that, in most cases, a misorientation of the order
      of several degrees exists between pearlite colonies within one ferrite nodule.
      Moreover, the ferrite matrix exhibits changes of crystallographic orientation
      inside colonies often accompanied by a network of low angle boundaries. The mean
      size of the ferrite nodule in the matrix was determined by means of electron
      backscatter diffraction. However, determination of the mean pearlite colony size
      was difficult and often impossible by means of both metallographic methods and
      electron backscatter diffraction measurements.

PMID- 17210059
TI  - Electron backscattered diffraction as a tool to quantify subgrains in deformed
      calcite.
AB  - In this work, we investigated processing methods to obtain subgrain sizes from
      electron backscattered diffraction data using samples of experimentally deformed
      calcite (CaCO(3)) polycrystals. The domain boundary hierarchy method, based on
      area measurements of domains enclosed by boundaries larger than a given
      misorientation angle, was applied to these calcite samples and was found to be
      limited by: (i) topological problems; (ii) undersampling of large grains; and
      (iii) artefacts caused by nonindexing. We tested two alternative methods that may
      reduce the problems: (i) the measured linear intercept hierarchy method, based on
      measurements of linear intercept between boundaries having larger misorientations
      than a given minimum angle; and (ii) the calculated linear intercept hierarchy
      method, based on the total length of boundaries having misorientations larger
      than a given minimum angle. The measured linear intercept hierarchy method was
      found to produce results more representative for the microstructure than the
      calculated linear intercept hierarchy method, because the calculated linear
      intercept hierarchy method has a significant uncertainty related to the grid
      based nature of the measurements. Preliminary results on calcite suggest that the
      measured linear intercept hierarchy method is related, in a complex way, to
      deformation conditions such as stress, strain and temperature as well as to the
      characteristics of subgrain rotation and grain boundary migration processes.

PMID- 17210060
TI  - Crystallization of poly(L-lactid acid) monitored by dielectric relaxation
      spectroscopy and atomic force microscopy.
AB  - An investigation was carried out on the crystallization process of poly(l-lactid
      acid) by dielectric relaxation spectroscopy and atomic force microscopy.
      Experimental results were generated by dielectric relaxation spectroscopy over a
      wide range of frequency and temperature in both the wholly amorphous state and
      during crystallization. The variation of the average relaxation time was studied
      during crystallization at 80 degrees C and the temperature dependence of this
      relaxation time for wholly amorphous and crystallized samples was analysed. This
      behaviour was modelled by Havriliak-Negami and Vogel-Fulcher equations. The
      sensitivity of the segmental dynamics to the degree of crystallinity was
      analysed, taking into account the relaxing segments and the thickness of the
      amorphous layer between lamellae. The morphologies obtained during
      crystallization processes at 80, 130 and 150 degrees C were monitored by atomic
      force microscopy at both the lamellar level and by analysing the multilayered
      superstructures formed. Hedrites, intermediate structures between single lamellar
      crystals and mature spherulites, were found to appear at the highest
      temperatures, whereas no evidence of hedrites was found at 80 degrees C, the
      spherulites seemed to be constructed from a framework of individual dominant
      lamellae that splay apart and branch. Complementary to the atomic force
      microscopy study, the evolution of the obtained morphologies was also followed by
      optical microscopy. Supporting evidence about the thermal behaviour of the
      polymers was obtained with differential scanning calorimetry.

PMID- 17210061
TI  - Digital image processing as a tool to monitor biomass growth in Aspergillus niger
      3T5B8 solid-state fermentation: preliminary results.
AB  - The estimation of biomass is an essential parameter for controlling fermentation
      processes. However, monitoring biomass growth in filamentous fungi solid-state
      fermentation is laborious. The aim of this study was to provide a better insight
      into the monitoring of biomass growth in Aspergillus niger 3T5B8 solid-state
      fermentation using a digital image-processing technique. The images were acquired
      with a stereomicroscope and a digital camera, and processed using KS400 software.
      Growth was evaluated every 24 h for 5 days, and quantified as the total area
      occupied by the hyphae. The correlation between the results of the proposed
      methodology and the polygalacturonase data was greater than 0.9, showing that a
      direct and linear relationship can be expected among these parameters. This work
      indicates that the digital processing technique can be used for indirect biomass
      estimation in a solid-state fermentation process.

PMID- 17210063
TI  - First combined electron backscatter diffraction and transmission electron
      microscopy study of grain boundary structure of deformed quartzite.
AB  - The structures of boundaries in a deformed and dynamically recovered and
      recrystallized quartz polycrystal (mylonite) were characterized by transmission
      electron microscopy, after the misorientation angles across the same grain
      boundaries had been analysed using electron backscatter diffraction in a scanning
      electron microscope. In this new approach, a specific sample area is mapped with
      electron backscatter diffraction, and the mapped area is then attached to a foil,
      and by the ion beam thinned for transmission electron microscopy analysis.
      Dislocations in grain boundaries were recognized as periodic and parallel
      fringes. The fringes associated with dislocations are observed in boundaries with
      misorientations less than 9 degrees , whereas such fringes cannot be seen in the
      boundaries with misorientations larger than 17 degrees . Some boundaries with
      misorientations between 9 degrees and 17 degrees generally have no structures
      associated with dislocation. One segment of a boundary with a misorientation of
      13.5 degrees has structures associated with dislocations. It is likely that the
      transition from low-angle to high-angle boundaries occurs at misorientations
      ranging from approximately 9 degrees to 14 degrees . Change in the grain boundary
      structure presumably influences the mobility of the boundaries. In the studied
      deformed quartz vein, a relative dearth of boundaries between misorientation
      angles of theta = 2 degrees and theta = 15 degrees has previously been reported,
      and high-angle boundaries form cusps where they intersect low-angle boundaries,
      suggesting substantial mobility of high-angle boundaries.

PMID- 17210062
TI  - Elemental distributions in femoral bone of rat under osteoporosis preventive
      treatments.
AB  - One of the abnormalities of bone architecture is osteoporosis as occurring in
      post-menopausal women. Especially long bones, such as femur, become more fragile
      and more prone to fracture. The efficiency of several osteoporosis preventative
      treatments based on oestrogen and progestin in bone structure and mineral
      recovery was studied using ovariectomized Wistar rats as an osteoporosis
      experimental model. Diagonal cross-sections of the proximal epiphysis of femoral
      bones were analysed using nuclear microscopy techniques in order to map and
      determine the concentration profiles of P, Ca, S, Fe and Zn from the epiphysis to
      diaphysis and across the cortical and trabecular bone structures. In control
      animals (not ovariectomized), the S and Zn contents significantly characterized
      differences between cortical and trabecular bone structures, whereas P and Ca
      showed increased gradients from the epiphyseal region to the diaphysis. After
      ovariectomy the differences observed were differential according to the type of
      hormonal supplementation. A significant decrease in P and Ca contents and
      depletion of minor and trace minerals, such as S, Fe and Zn, were found for both
      cortical and trabecular bone structures after ovariectomy relative to controls.
      Bone mineral contents were reversed to control levels by synthetic oestrogen
      supplementation, and combined oestrogen and progesterone treatment. Recovery was
      more evident in the femoral epiphysis and neck than in the diaphysis. The use of
      oestrogen alone did not lead to bone recovery after ovariectomy. Alterations in
      bone mineral composition observed for animals receiving synthetic oestrogen and
      combined oestrogen and progesterone supplement might reflect beneficial
      structural changes in critical regions of long bones, mostly affected in post
      menopausal osteoporosis.

PMID- 17210064
TI  - An improved method for angular-resolved characterization of the optical
      anisotropy of pyrolytic carbon.
AB  - A description is given of an experimental technique that improves the accuracy of
      the measurement of light extinctions by polarized light microscopy from deposits
      of pyrolytic carbon. The measurements were performed using a specially developed
      digital photometric image-analysis procedure providing high spatial and angular
      resolution of light extinctions over the reflecting optical domains with a high
      dynamic range of grey levels. The digital image acquisition and data processing
      are illustrated using circular-shaped pyrolytic carbon matrices of infiltrated
      carbon fibre felts and planar layers of pyrolytic graphite. The calculated value
      of the extinction angle for single crystalline graphite is discussed with respect
      to the experimental values for pyrolytic carbon with different degrees of optical
      anisotropy. Practical requirements for the accuracy of the method are discussed.

PMID- 17210065
TI  - Transmission electron microscope specimen preparation for exploring the buried
      interfaces in plan view.
AB  - A relatively easy and convenient process for the preparation of transmission
      electron microscope specimens of buried interfaces is described. The method is
      based on the alignment and realignment of the specimen rotation centre during ion
      milling. The ion-milling time interval in which good samples are obtained is
      substantially extended in this way.

PMID- 17210067
TI  - Photosynthesis: what color was its origin?
AB  - Recent studies using geological and molecular phylogenetic evidence suggest
      several alternative evolutionary scenarios for the origin of photosynthesis. The
      earliest photosynthetic group is variously thought to be heliobacteria,
      proteobacteria or a precursor of cyanobacteria, organisms whose photosynthetic
      pigments make them different colors.

PMID- 17210068
TI  - Clinical review: use of helium-oxygen in critically ill patients.
AB  - Use of helium-oxygen (He/O2) mixtures in critically ill patients is supported by
      a reliable and well understood theoretical rationale and by numerous experimental
      observations. Breathing He/O2 can benefit critically ill patients with severe
      respiratory compromise mainly by reducing airway resistance in obstructive
      syndromes such as acute asthma and decompensated chronic obstructive pulmonary
      disease. However, the benefit from He/O2 in terms of respiratory mechanics
      diminishes rapidly with increasing oxygen concentration in the gaseous mixture.
      Safe use of He/O2 in the intensive care unit requires specific equipment and
      supervision by adequately experienced personnel. The available clinical data on
      inhaled He/O2 mixtures are insufficient to prove that this therapy has benefit
      with respect to outcome variables. For these reasons, He/O2 is not currently a
      standard of care in critically ill patients with acute obstructive syndromes,
      apart from in some, well defined situations. Its role in critically ill patients
      must be more precisely defined if we are to identify those patients who could
      benefit from this therapeutic approach.

PMID- 17210069
TI  - Application of adenosine 5'-triphosphate (ATP) infusions in palliative home care:
      design of a randomized clinical trial.
AB  - BACKGROUND: Palliative care in cancer aims at alleviating the suffering of
      patients. A previous study in patients with advanced non-small-cell lung cancer
      showed that adenosine 5'-triphosphate (ATP) infusions had a favourable effect on
      fatigue, appetite, body weight, muscle strength, functional status and quality of
      life. The present study was designed 1. To evaluate whether ATP has favourable
      effects in terminally ill cancer patients, 2. To evaluate whether ATP infusions
      may reduce family caregiver burden and reduce the use of professional health care
      services, and 3. To test the feasibility of application of ATP infusions in a
      home care setting. METHODS/DESIGN: The study can be characterized as an open
      labelled randomized controlled trial with two parallel groups. The intervention
      group received usual palliative care, two visits by an experienced dietician for
      advice, and regular ATP infusions over a period of 8 weeks. The control group
      received palliative care as usual and dietetic advice, but no ATP. This paper
      gives a description of the study design, selection of patients, interventions and
      outcome measures. DISCUSSION: From April 2002 through October 2006, a total of
      100 patients have been randomized. Follow-up of patients will be completed in
      December 2006. At the time of writing, five patients are still in follow up. Of
      the 95 patients who have completed the study, 69 (73%) have completed four weeks
      of follow-up, and 53 (56%) have completed the full eight-week study period. The
      first results are expected in 2007.

PMID- 17210070
TI  - Craniocervical junction malformation in a child with Oromandibular-limb
      hypogenesis-Mobius syndrome.
AB  - We report a male child with Oromandibular-limb hypogenesis (OMLH), the main
      features being bilateral sixth and seventh nerve palsies, limb anomalies and
      hypoplasia of the tongue. Additional features were shortness of the neck
      associated with torticollis. Radiographs of the cervical spine were non
      contributory, but 3D computed tomography (CT) scanning of this area identified:
      a) congenital hypoplasia of the atlas; b) the simultaneous development of occiput
      atlas malformation/developmental defect. To our knowledge, this is the first
      clinical report assessing the cervico-cranium malformation in a child with OMLH
      Mobius syndrome.

PMID- 17210071
TI  - Measuring the psychosocial consequences of screening.
AB  - The last three decades have seen a dramatic rise in the implementation of
      screening programmes for cancer in industrialised countries. However, in contrast
      to screening for infectious diseases, most cancer screening programmes only have
      the potential to reduce mortality; they cannot lower the incidence of cancer in a
      population. In fact, most cancer screening programmes have been shown to increase
      the incidence of the disease as a consequence of over-diagnosis. A further
      dilemma of cancer screening programmes is that they do not distinguish between
      healthy people and those with disease. Rather, they identify a continuum of
      disease severity. Consequently, many healthy people who have abnormal screening
      tests are wrongly diagnosed. Indeed, studies have demonstrated that for each
      screening-prevented death from cancer, at least 200 false-positive results are
      given. Therefore, screening has the potential to be harmful as well as
      beneficial. The psychosocial consequences of false-positive screening results
      cannot be determined by diagnostic tests or by other technical means. Instead,
      patient reported outcome measures must be employed. To measure the outcomes of
      screening accurately and comprehensively patient reported outcome measures have
      to capture; the nature and extent of the psychosocial consequences and how these
      change over time. The outcome measures used must have high content validity and
      their psychometric properties should be determined prior to their use in the
      specific population. In particular it is important to establish
      unidimensionality, additivity and item ordering through the application of Item
      Response Theory.

PMID- 17210073
TI  - Separation of base allele and sampling term effects gives new insights in
      variance component QTL analysis.
AB  - BACKGROUND: Variance component (VC) models are commonly used for Quantitative
      Trait Loci (QTL) mapping in outbred populations. Here, the QTL effect is given as
      a random effect and a critical part of the model is the relationship between the
      phenotypic values and the random effect. In the traditional VC model, each
      individual has a unique QTL effect and the relationship between these random
      effects is given as a covariance structure (known as the identity-by-descent
      (IBD) matrix). RESULTS: We present an alternative notation of the variance
      component model, where the elements of the random effect are independent base
      generation allele effects and sampling term effects. The relationship between the
      phenotypic vales and the random effect is given by an incidence matrix, which
      results in a novel, but statistically equivalent, version of the traditional VC
      model. A general algorithm to estimate this incidence matrix is presented. Since
      the model is given in terms of base generation allele effects and sampling term
      effects, these effects can be estimated separately using best linear unbiased
      prediction (BLUP). From simulated data, we showed that biallelic QTL effects
      could be accurately clustered using the BLUP obtained from our model notation
      when markers are fully informative, and that the accuracy increased with the size
      of the QTL effect. We also developed a measure indicating whether a base
      generation marker homozygote is a QTL heterozygote or not, by comparing the
      variances of the sampling term BLUP and the base generation allele BLUP. A ratio
      greater than one gives strong support for a QTL heterozygote. CONCLUSION: We
      developed a simple presentation of the VC QTL model for identification of base
      generation allele effects in QTL linkage analysis. The base generation allele
      effects and sampling term effects were separated in our model notation. This
      clarifies the assumptions of the model and should also enhance the development of
      genome scan methods.

PMID- 17210072
TI  - A generalized analysis of hydrophobic and loop clusters within globular protein
      sequences.
AB  - BACKGROUND: Hydrophobic Cluster Analysis (HCA) is an efficient way to compare
      highly divergent sequences through the implicit secondary structure information
      directly derived from hydrophobic clusters. However, its efficiency and
      application are currently limited by the need of user expertise. In order to help
      the analysis of HCA plots, we report here the structural preferences of
      hydrophobic cluster species, which are frequently encountered in globular domains
      of proteins. These species are characterized only by their hydrophobic/non
      hydrophobic dichotomy. This analysis has been extended to loop-forming clusters,
      using an appropriate loop alphabet. RESULTS: The structural behavior of
      hydrophobic cluster species, which are typical of protein globular domains, was
      investigated within banks of experimental structures, considered at different
      levels of sequence redundancy. The 294 more frequent hydrophobic cluster species
      were analyzed with regard to their association with the different secondary
      structures (frequencies of association with secondary structures and secondary
      structure propensities). Hydrophobic cluster species are predominantly associated
      with regular secondary structures, and a large part (60 %) reveals preferences
      for alpha-helices or beta-strands. Moreover, the analysis of the hydrophobic
      cluster amino acid composition generally allows for finer prediction of the
      regular secondary structure associated with the considered cluster within a
      cluster species. We also investigated the behavior of loop forming clusters,
      using a "PGDNS" alphabet. These loop clusters do not overlap with hydrophobic
      clusters and are highly associated with coils. Finally, the structural
      information contained in the hydrophobic structural words, as deduced from
      experimental structures, was compared to the PSI-PRED predictions, revealing that
      beta-strands and especially alpha-helices are generally over-predicted within the
      limits of typical beta and alpha hydrophobic clusters. CONCLUSION: The dictionary
      of hydrophobic clusters described here can help the HCA user to interpret and
      compare the HCA plots of globular protein sequences, as well as provides an
      original fundamental insight into the structural bricks of protein folds.
      Moreover, the novel loop cluster analysis brings additional information for
      secondary structure prediction on the whole sequence through a generalized
      cluster analysis (GCA), and not only on regular secondary structures. Such
      information lays the foundations for developing a new and original tool for
      secondary structure prediction.

PMID- 17210074
TI  - Time for evidence-based cytology.
AB  - Evidence-based medicine (EBM) is a fashionable and an extremely hot topic for
      clinicians, patients and the health service planners. Evidence-based cytology
      (EBC) is an offshoot of EBM. The EBC is concerned with generating a reproducible,
      high quality and clinically relevant test result in the field of cytology. This
      is a rapidly evolving area with high practical importance. EBC is based entirely
      on research data. The various professional bodies on cytology design and
      recommend guidelines on the basis of evidences. Once the guideline is implemented
      and practiced then the experiences of the practicing cytopathologists may be used
      as a feed back to alter the existing guideline. The various facets of EBC are
      sampling and specimen adequacy, morphological identification and computer based
      expert system, integrated reporting, identification of the controversial areas
      and high quality researches for evidences. It is the duty of the individuals and
      institutions to practice EBC for better diagnosis and management of the patients.
      In this present paper, the various aspects of EBC have been discussed.

PMID- 17210075
TI  - The check-up: in-person, computerized, and telephone adaptations of motivational
      enhancement treatment to elicit voluntary participation by the contemplator.
AB  - Countless barriers come between people who are struggling with substance abuse
      and those charged with providing substance abuse treatment. The check-up, a form
      of motivational enhancement therapy, is a harm reduction intervention that offers
      a manner of supporting individuals by lowering specific barriers to reaching
      those who are untreated. The check-up was originally developed to reach problem
      drinkers who were neither seeking treatment nor self-initiating change. The
      intervention, marketed as an opportunity to take stock of one's experiences,
      involves an assessment and personalized feedback delivered with a counseling
      style termed motivational interviewing. Check-ups can be offered in care settings
      to individuals who, as a result of screening, manifest risk factors for specific
      disorders such as alcoholism. They can also be free-standing and publicized
      widely to the general public. This paper will discuss illustrations of in-person,
      computerized, in-school, and telephone applications of the free-standing type of
      check-up with reference to alcohol consumers, adult and adolescent marijuana
      smokers, and gay/bisexual males at risk for sexual transmission of HIV. The
      paper's major focus is to highlight how unique features of each application have
      the potential of reducing barriers to reaching specific at-risk populations. Also
      considered are key policy issues such as how check-up services can be funded,
      which venues are appropriate for the delivery of check-up interventions,
      pertinent competency criteria in evaluating staff who deliver this intervention,
      how marketing can be designed to reach contemplators in untreated at-risk
      populations, and how a check-up's success ought to be defined.

PMID- 17210076
TI  - Essential thrombocythemia.
AB  - Essential thrombocythemia (ET) is an acquired myeloproliferative disorder (MPD)
      characterized by a sustained elevation of platelet number with a tendency for
      thrombosis and hemorrhage. The prevalence in the general population is
      approximately 30/100,000. The median age at diagnosis is 65 to 70 years, but the
      disease may occur at any age. The female to male ratio is about 2:1. The clinical
      picture is dominated by a predisposition to vascular occlusive events (involving
      the cerebrovascular, coronary and peripheral circulation) and hemorrhages. Some
      patients with ET are asymptomatic, others may experience vasomotor (headaches,
      visual disturbances, lightheadedness, atypical chest pain, distal paresthesias,
      erythromelalgia), thrombotic, or hemorrhagic disturbances. Arterial and venous
      thromboses, as well as platelet-mediated transient occlusions of the
      microcirculation and bleeding, represent the main risks for ET patients.
      Thromboses of large arteries represent a major cause of mortality associated with
      ET or can induce severe neurological, cardiac or peripheral artery
      manifestations. Acute leukemia or myelodysplasia represent only rare and
      frequently later-onset events. The molecular pathogenesis of ET, which leads to
      the overproduction of mature blood cells, is similar to that found in other
      clonal MPDs such as chronic myeloid leukemia, polycythemia vera and myelofibrosis
      with myeloid metaplasia of the spleen. Polycythemia vera, myelofibrosis with
      myeloid metaplasia of the spleen and ET are generally associated under the common
      denomination of Philadelphia (Ph)-negative MPDs. Despite the recent
      identification of the JAK2 V617F mutation in a subset of patients with Ph
      negative MPDs, the detailed pathogenetic mechanism is still a matter of
      discussion. Therapeutic interventions in ET are limited to decisions concerning
      the introduction of anti-aggregation therapy and/or starting platelet
      cytoreduction. The therapeutic value of hydroxycarbamide and aspirin in high risk
      patients has been supported by controlled studies. Avoiding thromboreduction or
      opting for anagrelide to postpone the long-term side effects of hydrocarbamide in
      young or low risk patients represent alternative options. Life expectancy is
      almost normal and similar to that of a healthy population matched by age and sex.

PMID- 17210077
TI  - Update of the Anopheles gambiae PEST genome assembly.
AB  - BACKGROUND: The genome of Anopheles gambiae, the major vector of malaria, was
      sequenced and assembled in 2002. This initial genome assembly and analysis made
      available to the scientific community was complicated by the presence of assembly
      issues, such as scaffolds with no chromosomal location, no sequence data for the
      Y chromosome, haplotype polymorphisms resulting in two different genome
      assemblies in limited regions and contaminating bacterial DNA. RESULTS: Polytene
      chromosome in situ hybridization with cDNA clones was used to place 15 unmapped
      scaffolds (sizes totaling 5.34 Mbp) in the pericentromeric regions of the
      chromosomes and oriented a further 9 scaffolds. Additional analysis by in situ
      hybridization of bacterial artificial chromosome (BAC) clones placed 1.32 Mbp (5
      scaffolds) in the physical gaps between scaffolds on euchromatic parts of the
      chromosomes. The Y chromosome sequence information (0.18 Mbp) remains highly
      incomplete and fragmented among 55 short scaffolds. Analysis of BAC end sequences
      showed that 22 inter-scaffold gaps were spanned by BAC clones. Unmapped scaffolds
      were also aligned to the chromosome assemblies in silico, identifying regions
      totaling 8.18 Mbp (144 scaffolds) that are probably represented in the genome
      project by two alternative assemblies. An additional 3.53 Mbp of alternative
      assembly was identified within mapped scaffolds. Scaffolds comprising 1.97 Mbp
      (679 small scaffolds) were identified as probably derived from contaminating
      bacterial DNA. In total, about 33% of previously unmapped sequences were placed
      on the chromosomes. CONCLUSION: This study has used new approaches to improve the
      physical map and assembly of the A. gambiae genome.

PMID- 17210078
TI  - DiscoverySpace: an interactive data analysis application.
AB  - DiscoverySpace is a graphical application for bioinformatics data analysis. Users
      can seamlessly traverse references between biological databases and draw together
      annotations in an intuitive tabular interface. Datasets can be compared using a
      suite of novel tools to aid in the identification of significant patterns.
      DiscoverySpace is of broad utility and its particular strength is in the analysis
      of serial analysis of gene expression (SAGE) data. The application is freely
      available online.

PMID- 17210080
TI  - The Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) prisons project
      pilot study: protocol for a randomised controlled trial comparing dihydrocodeine
      and buprenorphine for opiate detoxification.
AB  - BACKGROUND: In the United Kingdom (UK), there is an extensive market for the
      class 'A' drug heroin. Many heroin users spend time in prison. People addicted to
      heroin often require prescribed medication when attempting to cease their drug
      use. The most commonly used detoxification agents in UK prisons are
      buprenorphine, dihydrocodeine and methadone. However, national guidelines do not
      state a detoxification drug of choice. Indeed, there is a paucity of research
      evaluating the most effective treatment for opiate detoxification in prisons.
      This study seeks to address the paucity by evaluating routinely used
      interventions amongst drug using prisoners within UK prisons. METHODS/DESIGN: The
      Leeds Evaluation of Efficacy of Detoxification Study (LEEDS) Prisons Pilot Study
      will use randomised controlled trial methodology to compare the open use of
      buprenorphine and dihydrocodeine for opiate detoxification, given in the context
      of routine care, within HMP Leeds. Prisoners who are eligible and give informed
      consent will be entered into the trial. The primary outcome measure will be
      abstinence status at five days post detoxification, as determined by a urine
      test. Secondary outcomes during the detoxification and then at one, three and six
      months post detoxification will be recorded.

PMID- 17210079
TI  - Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a
      randomised controlled trial.
AB  - BACKGROUND: Many drug users present to primary care requesting detoxification
      from illicit opiates. There are a number of detoxification agents but no
      recommended drug of choice. The purpose of this study is to compare buprenorphine
      with dihydrocodeine for detoxification from illicit opiates in primary care.
      METHODS: Open label randomised controlled trial in NHS Primary Care (General
      Practices), Leeds, UK. Sixty consenting adults using illicit opiates received
      either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing
      regimens for both interventions were at the discretion of prescribing doctor
      within a standard regimen of not more than 15 days. Primary outcome was
      abstinence from illicit opiates at final prescription as indicated by a urine
      sample. Secondary outcomes during detoxification period and at three and six
      months post detoxification were recorded. RESULTS: Only 23% completed the
      prescribed course of detoxification medication and gave a urine sample on
      collection of their final prescription. Risk of non-completion of detoxification
      was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35-0.96, p =
      0.065). A higher proportion of people allocated to buprenorphine provided a clean
      urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06
      CI 1.33-3.21, p = 0.028). People allocated to buprenorphine had fewer visits to
      professional carers during detoxification and more were abstinent at three months
      (10 vs 4, RR 1.55 CI 0.96-2.52) and six months post detoxification (7 vs 3, RR
      1.45 CI 0.84-2.49). CONCLUSION: Informative randomised trials evaluating routine
      care within the primary care setting are possible amongst drug using populations.
      This small study generates unique data on commonly used treatment regimens.

PMID- 17210081
TI  - IGFBP3 mRNA expression in benign and malignant breast tumors.
AB  - INTRODUCTION: Most previous studies have focused on evaluating the association
      between circulating insulin-like growth factor binding protein 3 (IGFBP-3) levels
      and breast cancer risk. Emerging evidence over the past few years suggests that
      IGFBP-3 may act directly on mammary epithelial cells. METHODS: To understand the
      role of IGFBP-3 in breast tumorigenesis, we investigated IGFBP3 mRNA expression
      levels in benign and malignant breast tumors and their adjacent normal tissues
      using real-time quantitative PCR. RESULTS: Cancer tissues had significantly lower
      IGFBP3 expression than benign tumor tissues (p < 0.001). IGFBP3 expressions in
      both tumor and adjacent tissues were higher in patients who had proliferative
      benign tumors than in those who had non-proliferative benign tumors. Among
      patients with benign breast disease, IGFBP3 expression in the tumor was
      significantly higher than that in their adjacent normal tissue. There were no
      apparent associations of IGFBP3 expression in cancer tissues with either overall
      survival or disease-free survival in a cohort of 521 patients with breast cancer.
      CONCLUSION: Our findings suggest that the expression level of IGFBP3 in breast
      tissues may be involved in breast tumorigenesis.

PMID- 17210082
TI  - Structure-based engineering of papillomavirus major capsid l1: controlling
      particle assembly.
AB  - The outer shell of the papillomavirus particle is comprised of 72 pentamers of
      the major capsid L1 protein arranged on a T = 7 icosahedral lattice. The
      recombinant L1 can form T = 7 virus-like particles in vitro. The crystal
      structure of a T = 7 papilloma virion has not yet been determined; however, the
      crystal structure of a T = 1 particle containing 12 pentamers is known. The T = 1
      structure reveals that helix-helix interactions, through three helices-h2, h3,
      and h4-near the C-terminus of L1, mediate the inter-pentameric bonding that is
      responsible for T = 1 assembly. Based on the T = 1 crystal structure, we have
      generated a set of internal deletions to test the role of the three C-terminal
      helices in T = 7 assembly. We have demonstrated that the h2, h3, and h4 near the
      C-terminal end of L1 are important for the L1 structure and particle assembly. In
      particular, we found that h2 and h3 are essential for L1 folding and pentamer
      formation, whereas h4 is indispensable for the assembly of not only T1, but also
      of the T7 virus-like particle.

PMID- 17210083
TI  - A sequence based synteny map between soybean and Arabidopsis thaliana.
AB  - BACKGROUND: Soybean (Glycine max, L. Merr.) is one of the world's most important
      crops, however, its complete genomic sequence has yet to be determined.
      Nonetheless, a large body of sequence information exists, particularly in the
      form of expressed sequence tags (ESTs). Herein, we report the use of the model
      organism Arabidopsis thaliana (thale cress) for which the entire genomic sequence
      is available as a framework to align thousands of short soybean sequences.
      RESULTS: A series of JAVA-based programs were created that processed and compared
      341,619 soybean DNA sequences against A. thaliana chromosomal DNA. A. thaliana
      DNA was probed for short, exact matches (15 bp) to each soybean sequence, and
      then checked for the number of additional 7 bp matches in the adjacent 400 bp
      region. The position of these matches was used to order soybean sequences in
      relation to the A. thaliana genome. CONCLUSION: Reported associations between
      soybean sequences and A. thaliana were within a 95% confidence interval of e(-30)
      e(-100). In addition, the clustering of soybean expressed sequence tags (ESTs)
      based on A. thaliana sequence was accurate enough to identify potential single
      nucleotide polymorphisms (SNPs) within the soybean sequence clusters. An EST,
      bacterial artificial chromosome (BAC) end sequence and marker amplicon sequence
      synteny map of soybean and A. thaliana is presented. In addition, all JAVA
      programs used to create this map are available upon request and on the WEB.

PMID- 17210085
TI  - Prevalence and clinical manifestations of gastro-oesophageal reflux-associated
      chronic cough in the Japanese population.
AB  - Gastro-oesophageal reflux (GOR) is one of the most common causes of chronic cough
      in Western countries, responsible for 10 to 40% of cases. In Japan, however, GOR
      associated chronic cough (GOR-CC) has been rarely reported and its clinical
      manifestation including frequency of concomitant reflux laryngitis is poorly
      known. We have analyzed prevalence and clinical characteristics of patients who
      were diagnosed as having GOR-CC among adult patients with chronic cough (>or= 8
      weeks) who visited our asthma and cough clinic over a period of 19 months.
      Diagnosis of GOR-CC was based on the response of coughing to a proton-pump
      inhibitor (lansoprazole) and/or positive results of 24 h ambulatory esophageal pH
      monitoring. Laryngeal involvement was based on symptoms or objective diagnosis by
      specialists.GOR-associated chronic cough was diagnosed in 7.1% (8 of 112) of
      chronic cough patients. In addition to the demographic data which were consistent
      with the characteristics of patients with GOR-CC in the Western populations,
      including gender (6 females), age (mean +/- SE, 56.9 +/- 5.8 years), duration of
      cough (9.9 +/- 3.3 months), lack of gastrointestinal symptoms (3 of 8) and
      complication with other causes of cough (5 of 8), we found the standard range of
      body mass index (23.9 +/- 1.5 kg/m2) and high incidence of concomitant reflux
      laryngitis (5 of 8) in the present 8 patients. Among 4 patients who could stop
      treatment with temporal resolution of cough, cough recurred in 3 patients, 1 week
      to 8 months after the discontinuation. In conclusion, GOR-CC is a less frequent
      cause of chronic cough in Japan than in Western countries. Signs or symptoms of
      laryngitis may be important as clues to suspicion of GOR-CC.

PMID- 17210084
TI  - The effects of second-hand smoke on biological processes important in
      atherogenesis.
AB  - BACKGROUND: Atherosclerosis is the leading cause of death in western societies
      and cigarette smoke is among the factors that strongly contribute to the
      development of this disease. The early events in atherogenesis are stimulated on
      the one hand by cytokines that chemoattract leukocytes and on the other hand by
      decrease in circulating molecules that protect endothelial cells (ECs) from
      injury. Here we focus our studies on the effects of "second-hand" smoke on
      atherogenesis. METHODS: To perform these studies, a smoking system that closely
      simulates exposure of humans to second-hand smoke was developed and a mouse model
      system transgenic for human apoB100 was used. These mice have moderate lipid
      levels that closely mimic human conditions that lead to atherosclerotic plaque
      formation. RESULTS: "Second-hand" cigarette smoke decreases plasma high density
      lipoprotein levels in the blood and also decreases the ratios between high
      density lipoprotein and low density lipoprotein, high density lipoprotein and
      triglyceride, and high density lipoprotein and total cholesterol. This change in
      lipid profiles causes not only more lipid accumulation in the aorta but also
      lipid deposition in many of the smaller vessels of the heart and in hepatocytes.
      In addition, mice exposed to smoke have increased levels of Monocyte
      Chemoattractant Protein-1 in circulation and in the heart/aorta tissue, have
      increased macrophages in the arterial walls, and have decreased levels of
      adiponectin, an EC-protective protein. Also, cytokine arrays revealed that mice
      exposed to smoke do not undergo the switch from the pro-inflammatory cytokine
      profile (that develops when the mice are initially exposed to second-hand smoke)
      to the adaptive response. Furthermore, triglyceride levels increase significantly
      in the liver of smoke-exposed mice. CONCLUSION: Long-term exposure to "second
      hand" smoke creates a state of permanent inflammation and an imbalance in the
      lipid profile that leads to lipid accumulation in the liver and in the blood
      vessels of the heart and aorta. The former potentially can lead to non-alcoholic
      fatty liver disease and the latter to heart attacks.

PMID- 17210086
TI  - Effects of altitude on circadian rhythm of adult locomotor activity in Himalayan
      strains of Drosophila helvetica.
AB  - BACKGROUND: We recently reported that the altitude of origin altered the photic
      and thermal sensitivity of the circadian pacemaker controlling eclosion and
      oviposition rhythms of high altitude Himalayan strains of Drosophila ananassae.
      The present study was aimed at investigating the effects of altitude of origin on
      the pacemaker controlling the adult locomotor activity rhythm of D. helvetica.
      METHODS: Locomotor activity rhythms of the high altitude Himalayan (haH) strain
      (Hemkund-Sahib, 4,121 m above sea level) and the low altitude Himalayan (laH)
      strain (Birahi, 1,132 m a.s.l.) of D. helvetica were assayed by two experiments.
      The first experiment examined the natural entrainment pattern in light-dark (LD)
      cycles at the breeding site of each strain. The second experiment examined the
      entrainment parameters in LD 12:12 cycles and the period of free-running rhythm
      in constant darkness (DD) under controlled laboratory conditions. RESULTS: When
      entrained by natural or artificial LD cycles, the haH strain had an unimodal
      activity pattern with a single peak that commenced in the forenoon and continued
      till evening, while the laH strain had a bimodal activity pattern in which the
      morning peak occurred before lights-on and was separated by about 4 h from the
      evening peak. Unimodality of the haH strain was retained in DD; however,
      bimodality of the laH strain was abolished in DD since the evening peak
      disappeared immediately after the trasfer from LD 12:12 to DD. The period of the
      free-running rhythm of the haH strain was ~26.1 h, whereas that of the laH strain
      was ~21.7 h. CONCLUSION: Parameters of entrainment and free-running rhythm of the
      adult locomotor activity of the haH strain of D. helvetica were strikingly
      different from those of the laH strain and were likely due to ecological
      adaptations to the prevailing environmental conditions at the altitude where the
      species evolved.

PMID- 17210087
TI  - Occurrence of protein structure elements in conserved sequence regions.
AB  - BACKGROUND: Conserved protein sequence regions are extremely useful for
      identifying and studying functionally and structurally important regions. By
      means of an integrated analysis of large-scale protein structure and sequence
      data, structural features of conserved protein sequence regions were identified.
      RESULTS: Helices and turns were found to be underrepresented in conserved
      regions, while strands were found to be overrepresented. Similar numbers of loops
      were found in conserved and random regions. CONCLUSION: These results can be
      understood in light of the structural constraints on different secondary
      structure elements, and their role in protein structural stabilization and
      topology. Strands can tolerate fewer sequence changes and nonetheless keep their
      specific shape and function. They thus tend to be more conserved than helices,
      which can keep their shape and function with more changes. Loop behavior can be
      explained by the presence of both constrained and freely changing loops in
      proteins. Our detailed statistical analysis of diverse proteins links protein
      evolution to the biophysics of protein thermodynamic stability and folding. The
      basic structural features of conserved sequence regions are also important
      determinants of protein structure motifs and their function.

PMID- 17210088
TI  - The peanut allergy epidemic: allergen molecular characterisation and prospects
      for specific therapy.
AB  - Peanut (Arachis hypogaea) allergy is a major cause of food-induced anaphylaxis,
      with increasing prevalence worldwide. To date, there is no cure for peanut
      allergy, and, unlike many other food allergies, it usually persists through to
      adulthood. Prevention of exposure to peanuts is managed through strict avoidance,
      which can be compromised by the frequent use of peanuts and peanut products in
      food preparations. Conventional subcutaneous-injection allergen immunotherapy
      using crude peanut extract is not a recommended treatment because of the risk of
      severe side effects, largely as a result of specific IgE antibodies.
      Consequently, there is an urgent need to develop a suitable peanut allergen
      preparation that can induce specific clinical and immunological tolerance to
      peanuts in allergic individuals without adverse side effects. This requires
      detailed molecular and immunological characterisation of the allergenic
      components of peanut. This article reviews current knowledge on clinically
      relevant peanut allergens, in particular Ara h 1, Ara h 2 and Ara h 3, together
      with options for T-cell-reactive but non-IgE-binding allergen variants for
      specific immunotherapeutic strategies. These include T-cell-epitope peptide and
      hypoallergenic mutant vaccines. Alternative routes of administration such as
      sublingual are also considered, and appropriate adjuvants for delivering
      effective treatments at these sites examined.

PMID- 17210090
TI  - Updated surgical experience with bone-anchored hearing aids in children.
AB  - BACKGROUND: We present the results of a retrospective review of children
      undergoing implantation with bone-anchored hearing aids (BAHAs) at the Great
      Ormond Street Hospital for Children. METHODS: The case notes of 71 children
      undergoing BAHA placement at the Great Ormond Street Hospital for Children
      between December 1990 and August 2002 were reviewed. Outcome measures included
      hearing thresholds, incidence of fixture loss, skin reaction and need for
      revision. Quality of life outcomes were also measured. RESULTS: Eighty-five ears
      had been implanted. Fifty-four per cent of children had experienced no
      complications, 42 per cent had required revision surgery and 26 per cent had
      experienced fixture loss at some point. Young age at implantation was associated
      with an adverse outcome. Trauma and failure of osseointegration had been the
      commonest reasons for failure. A skin reaction around the abutment had occurred
      at some point in 37 per cent of children but had persisted for longer than six
      months in only 9 per cent; this had been associated with fixture loss. The use of
      fixture site split skin grafts had reduced problems with skin hypertrophy and
      hair overgrowth. Hearing thresholds when using BAHAs had been comparable to those
      when using bone conduction hearing aids. However, BAHAs had significant
      additional benefits in terms of sound quality, ease of use and overall quality of
      life. CONCLUSION: Bone-anchored hearing aids provide significant benefits over
      other types of hearing aid, both audiologically and in terms of quality of life.
      Careful selection of candidates and meticulous follow up are required in order to
      minimize complications.

PMID- 17210091
TI  - Recurrent and residual juvenile angiofibromas.
AB  - INTRODUCTION: In the surgical management of juvenile nasopharyngeal angiofibromas
      the possibility of recurrences and residual tumours is always there. This study
      was undertaken to predict the prognostic factors determining recurrence of
      juvenile nasopharyngeal angiofibroma and to find out the usual sites of these
      tumours. MATERIAL AND METHODS: The medical records of 95 patients with
      histologically proven juvenile nasopharyngeal angiofibroma were reviewed
      retrospectively. The commonest surgical approach used was a combined transpalatal
      and transmaxillary approach with a lazy S incision. A conservative lateral
      infratemporal approach was used in three cases. RESULTS: Complete removal of the
      juvenile nasopharyngeal angiofibroma was achieved in 78 (82 per cent) of the
      cases in a single operation. A residual tumour was found in 17 (18 per cent)
      cases and recurrences occurred in 13 (13.7 per cent) cases. CONCLUSIONS:
      Extensions into the pterygoid fossa and basisphenoid, erosion of the clivus,
      intracranial extensions medial to the cavernous sinus, invasion of the sphenoid
      diploe through a widened pterygoid canal, feeders from the internal carotid
      artery, a young age and a residual tumour were risk factors found associated with
      recurrence of juvenile nasopharyngeal angiofibroma.

PMID- 17210092
TI  - Estimation of tracheostomy tube cuff pressure by pilot balloon palpation.
AB  - Two methods can be used to assess the intra-cuff pressure of tracheostomy tubes:
      digital palpation of the pilot balloon and use of a hand-held manometer. We
      conducted a telephone survey to determine the prevalence of both methods in
      intensive care units within 21 teaching hospitals across the United Kingdom.
      Forty-two per cent of the intensive care units surveyed used a protocol for
      monitoring cuff pressure with a manometer.A study to compare these two methods,
      using the manometer as the reference standard, was then carried out. The cuff
      pressure was correctly estimated in pre-inflated tracheostomy tubes, in a
      tracheal model, by 61 per cent of a cross-section of intensive care unit and
      otolaryngology staff.Using pilot balloon palpation is inaccurate and leaves a
      significant proportion of patients at risk of tracheal injury. We advocate the
      wider availability of hand-held pressure manometers in intensive care units and
      the institution of protocols for monitoring cuff pressure for any patient with a
      tracheostomy tube with an inflated cuff in situ.

PMID- 17210093
TI  - The effect of Egyptian honeybee propolis on the growth of Aspergillus versicolor
      and sterigmatocystin biosynthesis in Ras cheese.
AB  - Propolis is a natural product collected by honeybee workers. The product was
      tested for its antifungal effect against Aspergillus versicolor ATCC 12996 as
      well as biosynthesis of sterigmatocystin during ripening of Egyptian Ras cheese.
      The use of different concentrations of aqueous propolis extract 250, 500 and 1000
      part per million (ppm) on the cheese surface was investigated. Mould growth and
      toxin production were completely inhibited at the highest concentration 1000 ppm,
      while the lower concentrations exhibited definite fungistatic activity during 90
      days of ripening. Control cheese demonstrated that the amount of sterigmatocystin
      produced was proportional to the growth of Asp. versicolor during three months of
      ripening. It could be concluded that propolis concentration of 1000 ppm could
      prevent mould growth and sterigmatocystin production in Ras cheese. The economic
      as well as the public health importance of propolis as a natural preservative in
      cheese manufacture is discussed.

PMID- 17210094
TI  - [Subpopulations and cytokine expression of naive and memory T cells in normal
      human PBMCs].
AB  - AIM: To determine subpopulations and cytokine expression of naive and memory T
      cells by polychromatic flow cytometry(PFC). METHODS: PBMCs were separated from
      normal human peripheral blood and stimulated by superantigen (SEB). After
      incubation for 5 hours, the cells were fixed, permeablized and stained with
      multiplecolor-labeled mAbs for cell surface and intracellular cytokines. Then
      they were detected by polychromatic flow cytometry and the data were analyzed by
      Flow Jo software. RESULTS: Based on the expression of CD45RO molecules, CD4(+)
      and CD8(+) T cells were classified as naive and memory cells, which were further
      devided into several subsets according to the expression of CD62L and CCR7. When
      PBMCs were stimulated by SEB for 5 hours, CD45RO(+) and CD45RO(-) CD4(+) or
      CD8(+) T cells expressed IL-2, IFN-gamma and TNF-alpha. Further analysis
      indicated that CD62L(lo) CCR7(lo) and CCR7(+) T cells but not CD62L(hi) and
      CD62L(hi) CCR7(+) T cells expressed cytokines. In addition, the percentage of
      cytokine expression in CD62L(lo) CCR7(lo) subsets was markedly higher than that
      in CCR7(+) subsets. CONCLUSION: It is not scientific to identify naive and memory
      cells in human T cells only based on the expression of CD45RO. Accurate
      determination of naive, effector and memory cell populations can be achieved not
      only based on the expression of CD45RO but also according to the expression of
      CD62L.

PMID- 17210095
TI  - [Effect of p53 on the variation of renal tubular epithelial cells after kidney
      ischemia/reperfusion injury].
AB  - AIM: To observe the variation of renal tubular epithelial cells in p53(+/+) and
      p53(-/-) mice with young or old age at different time after kidney
      ischemia/reperfusion injury (IRI), and to investigate the contribution of p53
      gene in the variation. METHODS: p53(+/+) and p53(-/-) male mice at age of 2 and
      12 months were made ischemic by clamping left renal hila for 45 min. At 0, 1, 3
      and 7 d, 1, 3 and 6 month after reflow, renal tissues were processed for
      morphometric observation and proliferating cell nuclear antigen(PCNA), apoptosis
      and senescence-associated beta-galactosidase (SA-beta-gal) analysis, using
      hematoxylin and eosin stain, immunohistochemistry, terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin in situ nick-end labeling (TUNEL) and
      histochemical staining, respectively. RESULTS: Renal tubule necrosis was more
      severely in p53(-/-) mice and aged mice compared to p53(+/+) mice and young mice
      (P<0.05), respectively. Apoptotic cells in p53(+/+) mice increased obviously
      compared to p53(-/-) mice (P<0.05) at 7 d after IRI. In young wild-type mice,
      occasionally faint staining for SA-beta-gal activity began to appear at 1 month,
      and obviously significantly increased at 3 and 6 months after IRI (P<0.05), but
      in contralateral kidney at any time as mentioned above, and in the IRI kidneys in
      p53(-/-) mice at 1 and 3 months, there was almost no positive staining for SA
      beta-gal; occasionally positive staining for SA-beta-gal was observed in the IRI
      kidney in p53(-/-) mice at 6 months after IRI. In p53 (-/-) and p53(+/+) aged
      mice, both kindeys had positive staining for SA-beta-gal activity at 0 d after
      IRI, but the level of the activity in p53(-/-) mice was much more lower than that
      in p53(+/+) mice (P<0.05), then the level of the activity decreased notably at 1
      d in the IRI kidney (P<0.05). Positive stain of nuclear PCNA in p53(+/+) young
      mice had no statistical significance compared to p53(+/+) aged mice (P>0.05). But
      in p53(-/-) mice, significant positive staining for PCNA was tested, especially
      in young mice and in IRI kidneys (P>0.05). Correlation analysis between senescent
      and apoptotic cells in aged mice was made at 1 d after IRI, then striking
      negative correlation was found between both of them in p53(+/+) mice (r=-0.82,
      P<0.05), but no statistical correlation in p53(-/-) mice (r=0.26, P>0.05).
      CONCLUSION: IRI can accelerate renal tubular cell senescence and cellular
      death(both necrosis and apoptosis)after that. p53 gene may play an important role
      in the variation of tubular epithelial cells after kidney IRI.

PMID- 17210096
TI  - [Influence of bifidobacterium DNA on PKC and NF-kappaB in murine macrophages].
AB  - AIM: To explore the influence of DNA of bifidobacteriua adolescence on PKC and NK
      kappaB of murine macrophages. METHODS: The fluorescent intensity of PKCalpha,
      PKCbetaI, PKCbetaII, PKCgamma, PKCepsilon and PKCzeta in murine peritoneal
      macrophages was detected by using laser confocal microscope. The density of NK
      kappaB(+) macrophages was detected by immunocytochemical staining. RESULTS: The
      average fluorescent intensity of PKCalpha and PKCbetaII produced by mouse
      peritoneal macrophages in bifidobacterium DNA injection group was markedly higher
      than that in control group(P<0.01). There was no statistically significant
      difference of average fluorescent intensity of PKCbetaI, PKCgamma, PKCepsilon and
      PKCzeta between the two groups (P>0.05). The density of NK-kappaB(+) macrophages
      in bifidobacterium DNA injection group was markedly higher than that in control
      group (P<0.01). CONCLUSION: DNA of bifidobacteria adolescence could activate
      macrophages by promoting the activity of PKCalpha, PKCbetaII and NF-kappaB.

PMID- 17210097
TI  - [Effect of siRNA transfection targeting VEGF gene on proliferation and apoptosis
      of human breast cancer cells].
AB  - AIM: To explore the effect of RNA interference-mediated vascular endothelial
      growth factor (VEGF) gene silencing on proliferation and apoptosis of human
      breast cancer MCF-7 cells. METHODS: Small interfering RNA (siRNA) targeting VEGF
      gene was designed and DNA template was synthesized, then siRNA was obtained by in
      vitro transcription. After ds-siRNA was transfected into MCF-7 cells with
      Lipofectamine, the proliferation of MCF-7 cells was detected by MTT colorimetry,
      and the apoptosis was measured by Hoechst33258 staining. The change of cell cycle
      was analyzed by flow cytometry (FCM). The expression of VEGF on mRNA and protein
      level was analyzed by RT-PCR and immunohistochemical technology respectively.
      RESULTS: The siRNA targeting human VEGF gene effectively inhibited the
      proliferation of MCF-7 cells, induced cell apoptosis, arrested the cell cycle in
      G(0)/G(1) phase, and decreased the expression of VEGF on both mRNA and protein
      level. But these effects did not appear in scrambled siRNA (siRNA(SCR)) control
      group. CONCLUSION: The siRNA targeting human VEGF gene could reduce VEGF
      expression, inhibit cellular proliferation and induce apoptosis in MCF-7 cells in
      vitro.

PMID- 17210098
TI  - [Construction and expression of eukaryotic coexpression plasmid containing human
      MUC1 gene and GM-CSF gene].
AB  - AIM: To construct an eukaryotic coexpression plasmid containing the coding region
      of human MUC1 tandem repeats gene and GM-CSF gene and to identify its expression
      in COS-7 cell. METHODS: MUC1 tandem repeats gene was obtained by synthesizing the
      segments. After identified by restriction endonuclease digestion analysis and DNA
      sequencing, MUC1 tandem repeats gene and GM-CSF gene were cloned into eukaryotic
      expression vector pcDNA3.1(+) to construct recombinant plasmid pcDNA3.1(+)-MUC1
      GM-CSF. Then the recombinant plasmid was transfected into COS-7 cell by
      electroporation and the expression of target gene was detected by
      immunoflourescence and ELISA. RESULTS: Restriction analysis and DNA sequencing
      showed that the recombinant plasmid contained the coding region of human MUC1
      tandem repeats gene and GM-CSF gene. The expression of MUC1 and GM-CSF was
      detected. CONCLUSION: The suuessful construction and expression of recombinant
      plasmid pcDNA3.1(+)-MUC1-GM-CSF lay a foundation for further development of DNA
      vaccine against breast cancer.

PMID- 17210099
TI  - [Construction and prokaryotic expression of recombinant gene EGFRvIII HBcAg and
      immunogenicity analysis of the fusion protein].
AB  - AIM: To construct recombinant prokaryotic expression plasmid pET28a(+)/c-PEP-3-c
      and evaluate the immunogenicity of the fusion protein. METHODS: cDNA fragment
      encoding PEP-3 was obtained from pGEM-T Easy/PEP-3 and inserted into recombinant
      plasmid pGEMEX/HBcAg. Then it was subcloned in prokaryotic expression vector and
      transformed into E.coli BL21(DE3). The fusion protein was expressed by inducing
      IPTG and purified by Ni(2+)-NTA affinity chromatography. BALB/c mice were
      immunized with fusion protein and the antibody titre was determined by indirect
      ELISA. RESULTS: The recombinant gene was confirmed to be correct by restriction
      enzyme digestion and DNA sequencing. After prokaryotic expression, fusion protein
      existed in sediment and accounted for 56% of all bacterial lysate. The purified
      product accounted for 92% of all protein and its concentration was 8 g/L. The
      antibody titre in blood serum reached 1:16 000 after the fourth immunization and
      reached 1:2.56x10(5) after the sixth immunization. The titre of anti-PEP-3
      antibody reached 1:1.28x10(5) and the titre of anti-HBcAg antibody was less than
      1:4x10(3). CONCLUSION: Fusion gene PEP-3-HBcAg is highly expressed in E.coli
      BL21. The expressed fusion protein can induce neutralizing antibody with high
      titer and specificity, which lays a foundation for the study of genetically
      engineering vaccine for malignant tumors with the high expression of EGFRvIII.

PMID- 17210100
TI  - [Construction of the expression vector pET32a/His MBL-CLR and its expression in
      E.coli].
AB  - AIM: To construct pET32a/His MBL-CLR recombinant prokaryotic expression plasmid
      and to express mannan-binding lectin-CLR (MBL-CLR) protein in E.coli METHODS: The
      human MBL-CLR gene was amplified by PCR from pGEM-MBL plasmid, and was inserted
      into prokaryotic expression vector pET32a. After identified by restriction
      mapping and sequencing, the recombinant plasmid pET32a/His MBL-CLR was
      transformed into E.coli BL21 (DE3) cells. The expressed product was purified by
      Immobilized Metal Affinity Chromatography (IMAC) and identified by SDS-PAGE,
      Western blot and indirect enzyme-linked immunosorbent assay (ELISA) using the
      antibody from BALB/c mice immunized with the recombinant human MBL protein.
      RESULTS: The cDNA fragment of 180 bp was amplified from pGEM-MBL plasmid and the
      recombinant expression vector pET32/His MBL-CLR was constructed. The recombinant
      plasmid was consistent with those expected by restriction maps and sequence.
      Three components of relative molecular mass 30,000, 60,000 and 120,000 in the
      purified recombinant product were detected by SDS-PAGE and all the components
      could be recognized by anti-6His antibody in Western blot assay. The three
      components were correspondingly with the band of the monomer and oligomer of the
      fusion protein. The purified recombinant product could react with the antibody
      against the recombinant human MBL protein in the indirect ELISA. CONCLUSION: The
      prokaryotic expression strains that efficiently express recombinant human MBL-CLR
      and the recombinant human MBL-CLR-Trx fusion protein were obtained successfully,
      which will help the further structure-function research of MBL molecule.

PMID- 17210101
TI  - [Cloning and eukaryotic expression of murine beta-defensin-2(mBD-2)].
AB  - AIM: To clone murine beta defensin-2 gene (mBD2) and to express the mBD2 protein
      eukaryotically. METHODS: Total RNA was isolated from the lungs of BALB/c mice
      which were injected with LPS in advance. The DNA fragment encoding mBD2 was
      amplified by RT-PCR and inserted into the plasmid pcDNA3.1(+), which was then
      digested with EcoR I and Xho I to construct the recombinant plasmid,
      pcDNA3.1(+)/mBD2. The pcDNA3.1(+)/mBD2 was identified by endonuclease digestion,
      PCR, and sequencing analysis. The SiHa cells were transfected with
      pcDNA3.1(+)/mBD2 plasmid and screened by G418 of 100 mg/L over 20 days. Steady
      expression of mBD2 was confirmed by immunofluorescent staining and RT-PCR.
      RESULTS: About 250 bp DNA fragment was amplified by RT-PCR from lung total RNA of
      the mice injected with LPS. The eukaryotic expression vector, pcDNA3.1(+)/mBD2,
      was successfully constructed after inserting the mBD2 fragment into pcDNA3.1(+).
      Most of SiHa cells transfected with pcDNA3.1(+)/mBD2 and screened by G418 could
      express the mBD2 protein, confirmed by immunofluorescent staining and RT-PCR.
      CONCLUSION: The eukaryotic vector of pcDNA3.1(+)/mBD2 was successfully
      constructed and transfected into SiHa cells, which established a solid foundation
      for further study on the biological characteristics and anti-tumor mechanisms of
      the mBD2 protein.

PMID- 17210102
TI  - [Premature delivery induced by LPS in syngenetically impregnated BALB/c and
      NOD/SCID mice].
AB  - AIM: To extend understanding of the mechanism of lipopolysaccharide (LPS)-induced
      preterm delivery in syngenetically impregnated BALB/c and NOD/SCID (nonobese
      diabetic/severe combined immunodeficiency) mice. METHODS: Strategies of LPS
      stimulation were pursued with or without previous Toll-like receptor 4 (TLR4)
      blocking. The incidence of LPS-induced preterm delivery and fetal death were
      compared between the BALB/c and NOD/SCID groups. Guided by the time when all
      expected preterm deliveries have occurred in the first experiment (i.e., day 16
      of gestation), the LPS-stimulated mice, with or without previous TLR4 blocking,
      were killed at the beginning of preterm labor and pooled placentas were collected
      in each mouse in the second experiment. The expression of cell surface TLR4,
      CD80, and intracellular TNF-alpha in placenta CD45(+) cell population was
      determined by flow cytometry(FCM). RESULTS: It displayed that preterm delivery
      could be induced by LPS in BALB/c mice, while the NOD/SCID mice seemed to be
      resistant to LPS induction. Upon LPS stimulation, TLR4 expression was not changed
      either in BALB/c or in NOD/SCID mice, but the CD45(+) CD80(+) cell percentage was
      elevated in both groups. However, the CD45(+) TNF-alpha(+) cell percentage was
      increased merely in BALB/c mice after stimulation, while no such trend was
      observed in NOD/SCID mice. In BALB/c mice, the effect of LPS on CD80 and TNF
      alpha expression could be abrogated by previous TLR4 blocking, which subsequently
      prevented LPS-induced preterm delivery. CONCLUSION: Although LPS do not alter
      TLR4 expression, it interacts with this receptor, triggers the mobilization of
      CD45(+) CD80(+) cells, results in elevated production of inflammatory cytokines,
      and finally results in preterm delivery. The diversity of sensitivity to LPS
      induction observed in BALB/c and NOD/SCID mice implies that the lack of
      functional T and NK cells in the NOD/SCID may be the reason why the NOD/SCID
      appeared to be resistant to LPS-induced premature labor.

PMID- 17210103
TI  - [Induction and mechanism study of anti-melanoma immune response by M.
      tuberculosis Ag85B].
AB  - AIM: To study the anti-melanoma immunity efficacy of Ag85B antigen gene therapy
      in vivo. METHODS: C57BL/6 mice were inoculated s.c. with B16 cells, and 8 days
      later the mice were inoculated s.c. again with B16 cells (control group 1),
      B16/pcDNA3 cells (control group 2) or B16/pcDNA3-Ag85B cells (experimental
      group), respectively. Tumor volume, survival time, serum IFN-gamma level and IL-4
      level of 3 groups mice were observed. Antitumor activity of Ag85B was studied.
      RESULTS: From 12 to 23 day, the mean tumor volume of mice increased from 1.1058
      cm(3) and 0.9123 cm(3) to 7.5983 cm(3) and 5.8746 cm(3) in the control group 1
      and 2, respectively. But it increased from 0.5158 cm(3) to 1.5080 cm(3) in the
      experimental group. The mean survival time of mice was 24.1 days and 24.7 days in
      the control group 1 and 2, respectively. That was 27.8 days in the experimental
      group. Within 13 days after the last inoculation, the serum IFN-gamma level of
      all groups experienced increased (That increased to 26.3 ng/L, 23.0 ng/L and 25.2
      ng/L in the control group 1, 2 and the experimental group, respectively).
      Subsequently, the serum IFN-gamma level in the two control groups decreased (That
      decreased to 19.3 ng/L and 18.3 ng/L in the control group 1 and 2) while it still
      augmented in the experimental group (That increased to 46.5 ng/L). IL-4 level was
      slightly but not significantly enhanced and then declined in all mice.
      CONCLUSION: Ag85B induced the increase of serum IFN-gamma level in the animals
      experiments, inhibited the tumor growth and prolonged the survival of the tumor
      bearing mice.

PMID- 17210104
TI  - [Effect of ST6Gal I siRNA-mediated gene silencing on the adhesion and invasion of
      SW480 cells].
AB  - AIM: To study the effect of synthesized ST6Gal I specific siRNA on the adhesion
      and invasiveness of human colon carcinoma cell line SW480 with over expression of
      ST6Gal I. METHODS: A double strand small interference RNA (siRNA) targeting
      ST6Gal I was designed and synthesized, and then transfected into SW480 cells by
      lipofectmine 2000. SW480 cells were cultured and divided into 4 groups: blank
      control group, liposome control group, non-specific siRNA group and ST6Gal I
      siRNA group. The expression of ST6Gal I mRNA was examined by RT-PCR and the
      amount of alpha-2, 6-sialylation on the SW480 cell surface was detected by flow
      cytometry. The adhesion and invasion of SW480 cells to extracellular matrix (ECM)
      were analyzed by using CytoMatrix kit and cell invasion assay kit, respectively.
      RESULTS: After SW480 cells were transfected for 48 hours, the expression of
      ST6Gal I mRNA in ST6Gal I siRNA group was significantly decreased compared with
      that in the blank control group, liposome control group, and non-specific siRNA
      group (P<0.05). After SW480 cells were transfected for 72 hours, the amount of
      alpha-2, 6-sialylation on cell surface, the adhesion and invasion of the cells in
      ST6Gal I siRNA group were markedly lower than those in the other 3 groups
      (P<0.05). CONCLUSION: The chemically synthesized specific siRNA targeting ST6Gal
      I can effectively inhibit the expression of ST6Gal I and reduce cell adhesion and
      invasion to ECM in SW480 cells. Our research is important for further study of
      anti-tumor treatment with RNA interference.

PMID- 17210105
TI  - [Effect of daqingye on EP3 mRNA expression of hypothalamus in IL-1beta-induced
      rabbits].
AB  - AIM: To study the antipyretic effect and mechanism of Daqingye injection (DQYI).
      METHODS: The IL-1beta-induced febrile New Zealand rabbits were chosen as
      experimental models and the antipyretic effect of DQYI was observed. The
      expression of EP3 mRNA was investigated by using in situ hybridization (ISH) in
      POAH. RESULTS: First, the colonic temperature went up gradually after
      intravenous(i.v) IL-1beta. The peak value of temperature(deltaT) and thermal
      response index (TRI(1)) in IL-1beta-treated group were higher than those in
      control group (P<0.01). The DeltaT and TRI(1) of in DQYI and IL-1beta- treated
      group were lower than those in IL-1beta-treated group (P<0.05). The temperature
      of DQYI-treated group showed no distinguished difference compared with that in
      control group (P>0.05). Second, the expression of EP3 mRNA in the POAH of IL-
      1beta-treated group increased markedly compared with that in control group
      (P<0.01). The expression of EP3 mRNA treated by IL-1beta+DQYI in the POAH
      decreased strikingly compared with that in IL-1beta group(P<0.05). CONCLUSION:
      DQYI has distinct antipyretic effect on IL-1beta-induced fever. The mechanism
      might be the inhibition of EP3 mRNA expression in POAH from rabbits.

PMID- 17210106
TI  - [The effects of vascular endothelial growth factor on dendritic cells in
      esophageal tumor tissue].
AB  - AIM: To investigate the relationship between vascular endothelial growth factor
      (VEGF) and S100 protein positive dendritic cell (DC) in esophagelal tumor tissue.
      METHODS: VEGF and S100 protein in 94 patients with esophageal carcinoma were
      detected by HRP Labelled streptavidin biotin(LSAB) immunohistochemical method.
      RESULTS: Postive rate of VEGF in esophageal tumor tissues was 74.46%(70/94); and
      the later the clinical stage and the lower the differentiation level was the more
      VEGF was(r=0.864, 0.803, respectively; P<0.05); while the later the clinical
      stage and the lower the differentiation level was, the less number of S100(+) DCs
      existed (r=-0.763, -0.908, respectively; P<0.05). Furthermore, there was a
      reverse correlation between the expression of VEGF and S100(+) DC (r=-0.817,
      P<0.05). CONCLUSION: There may be a reverse relationship between the expression
      of VEGF and S100(+) DC in esophageal tumor tissue, VEGF could decrease the number
      of S100(+) DC and impair the immunological function of the body.

PMID- 17210107
TI  - [Effects of Dengue virus infection on PGIS expression and PGI2 secretion of human
      vascular endothelial cells].
AB  - AIM: To elucidate the effects of Dengue virus on the expression and secretion of
      prostacyclin (PGI(2)) in endothelial cells. METHODS: Cultured human umbilical
      vein endothelial cells (HUVEC) were infected by Dengue virus II(DV(2)) for
      different duration. PGI(2) level in the supernatant was determined by radioimmune
      assay. Cytoplasmic RNA of the infected HUVEC was prepared using the Trizol method
      and was assayed for prostacyclin synthase (PGIS) by RT-PCR. RESULTS: PGIS
      expression as well as PGI(2) secretion of the DV(2) group were significantly
      increased (P<0.05) at 48 h, 72 h and 96 h post-infection compared to the control
      group. CONCLUSION: DV(2) could promote the expression of PGIS mRNA in HUVEC and
      increase the level of PGI(2), which may increase the vascular permeability. The
      dysfunction of vascular endothelial cell (EC) induced by DV may be related to the
      pathogenesis of Dengue haemorrhagic fever (DHF) and Dengue shock syndrome(DSS).

PMID- 17210108
TI  - [Study on therapy of experimental autoimmune neuritis by bone marrow stromal
      cells].
AB  - AIM: To investigate the therapeutic effect of bone marrow stromal cells (BMSCs)
      transplantation on experimental autoimmune neuritis (EAN) and study the possible
      mechanism. METHODS: EAN model was established by immunizing Lewis rats with
      P(0)180-199 peptide and complete Freund's adjuvant (CFA). In the therapy group,
      BMSCs (2x10(6) cells/rat) were marked with fluorochrome PKH26 and injected into
      the rats' caudal vein 10 d after immunization. The therapeutic effect of BMSC
      transplantation on EAN rats was investigated by clinical assessment,
      immunohistochemical staining, and ELISA, respectively. RESULTS: The injected
      BMSCs could migrate to the demyelinated nerve tissues, and the demyelination and
      inflammatory infiltration was relieved. The infiltration of CD4(+) and CD8(+) T
      cells and the sera level of IFN-gamma and TNF-alpha were decreased significantly
      (P<0.05), whereas IL-4 level in the supernatant of cultured lymphocytes was
      increased (P<0.05). CONCLUSION: Certain therapeutic effect of BMSC
      transplantation on EAN was observed. BMSCs could reverse the disbalance of
      Th1/Th2 cells by regulating the cytokine expression and could inhibit the
      activation and proliferation of T cells.

PMID- 17210109
TI  - [Preventive and therapeutic effects of qiongyugao on hepatocellular carcinoma via
      inhibition of the expression of HBxAg in hepatic carcinoma cells].
AB  - AIM: To investigate the effects of qiongyugao on the expression of hepatitis B x
      antigen (HBxAg) in BALB/c-nu mice into which human hepatic carcinoma cells were
      transplanted, and to analyze its specific mechanism in prophylaxis and treatment
      of hepatocellular carcinoma. METHODS: A nude mouse model with the transplantation
      of human hepatic carcinoma cells was established to observe the preventive and
      therapeutic effects of qiongyugao on the body weight and tumor weight of the
      mice. The expression of HBxAg in tumor and liver tissue wsa detected by
      immunohistochemical studies. RESULTS: Compared with model control group,
      prophylaxis and treatment with qiongyugao increased the body weight, depressed
      the tumor weight and inhibited HBxAg expression. The same efficacy was showed in
      both qiongyugao prophylaxis group and cyclophosphamide treatment group.
      CONCLUSION: Qiongyugao can slow down the growth of tumor and inhibit the
      expression of HBxAg, which may be an essential mechanism in prophylaxis and
      treatment of hepatocellular carcinoma.

PMID- 17210110
TI  - [Induction of specific CTL by DC from axillary lymph node of patients with breast
      cancer].
AB  - AIM: To investigate the capability of the dendritic cells (DC) from axillary
      draining lymph node of patients with breast cancer to induce the antigen specific
      CTL. METHODS: The mononuclear cells were isolated from axillary draining lymph
      node, and the adherent cells were cultured with rhGM-CSF and rhIL-4 to induce DC.
      The non-adherent cells were cultured with IL-2 to induce tumor draining lymph
      node cells(TDLNC). DCs stimulated by the autoallergic breast cancer freeze
      thawing antigen were co-cultured with the obtained TDLNC to induce tumor antigen
      specific CTL. RESULTS: The positive percentage of CD1a, CD83, CD86 on DC from
      freshly isolated mononuclear cells in axillary draining lymph node was 11.0+/
      2.3, 26.6+/-5.2 and 33.0+/-6.1, respectively. After co-cultured with rhGM-CSF,
      rhIL-4, breast cancer freeze-thawing antigen and TNF-alpha, the percentage of
      CD1a, CD83, CD86 was increased to 50.2+/-5.7, 60.5+/-16.5 and 56.2+/-16.4,
      respectively, (P<0.01). The percentage of CD8(+) T cells in TDLNC increased from
      32.8+/-3.2 to 62.5+/-2.5 after co-cultured with DC-Ag (P<0.01). CONCLUSION:
      Typical DCs can be induced from the mononuclear cells in axillary draining lymph
      node after stimulated with cytokine (rhGM-CSF, rhIL-4 and TNF-alpha), which
      possess strong antigen presentation function and can stimulate TDLNC to
      proliferate and differentiate into antigen specific CTL.

PMID- 17210111
TI  - [Construction of phage antibody library with predetermined CDR3 gene and
      screening of humanized Fab of anti-human integrin alphanubeta3 monoclonal
      antibody].
AB  - AIM: To construct phage antibody library with predetermined CDR3 and to screen
      humanized Fab of anti-human integrin alphanubeta(3) monoclonal antibody (mAb) by
      epitope guided selection. METHODS: LCDR3 gene of mAb E10 was inserted into human
      light chain variable region gene library. Hybrid phage antibody library was
      constructed by cloning E10 chimeric Fd gene and human light chain variable region
      gene into pComb3. Humanized light chain gene was obtained by screening against
      human integrin alphanubeta(3). Likewise, humanized Fab were gained by panning
      human phage antibody library, which was constructed by cloning humanized light
      chain gene and human heavy chain Fd gene with E10 HCDR3 into pComb3. RESULTS:
      Three humanized Fab clones was obtained by screening hybrid phage antibody
      library and human phage antibody library, which contained 2.1x10(6), 2x10(7)
      colony forming units, respectively. Indirect ELISA and competitive inhibition
      ELISA analysis demonstrated that three humanized Fab antibody had specific
      binding activity with human integrin alphanubeta(3). The strongest anti-human
      integrin alphanubeta(3) reactive D5 clone was sequenced and sequencing analysis
      showed that the V(kappa) and V(H) were derived from VKIII and VHI, respectively.
      CONCLUSION: Humanized Fab of anti-human integrin alphanubeta(3) mAb has been
      successfully obtained by phage display technology which lays the foundation for
      further clinical research.

PMID- 17210112
TI  - [Preparation and preliminary application of monoclonal antibody against alpha
      zearalanol].
AB  - AIM: To prepare monoclonal antibody (mAb) against alpha-zearalanol (alpha-ZER)
      and develop an immunoassay for the detection of alpha-ZER and its analogues
      residues in food derived from animal tissues. METHODS: alpha-ZER was conjugated
      to BSA as immunogen to immunize BALB/c mice and mAb were prepared by hybridoma
      technique. mAb's characteristics (titer, Ig subclass, specificity and relative
      affinity) were identified by ELISA. Standard inhibitive cure was made and
      sensitivity of the mAb was identified. 37 samples derived from animal liver were
      detected for alpha-ZER residues by competitive ELISA established in the study.
      RESULTS: 8 hybridoma cell lines stably secreting anti-alpha-ZER mAb were
      obtained. The titer of one of them (4E5) was 5.142x10(7). The Ig subclass was
      IgG1. The mAb was specific for alpha-ZER and its analogues and had no cross
      reactivity with other compounds.8 positive results were found from the 37 samples
      derived from animal liver which were negative detected by HPLC. CONCLUSION: Anti
      alpha-ZER mAb has been prepared successfully. A rapid method using the mAb for
      detecting alpha-ZER and its analogues residues in animal tissues has been
      established.

PMID- 17210113
TI  - Maintaining readiness for mental rotation interferes with perceptual processes in
      children but with response selection in adults.
AB  - Previous work revealed that mental rotation is not purely inserted into a same
      different discrimination task. Instead, response time (RT) is slowed to upright
      stimuli in blocks containing rotated stimuli compared to RT to the same upright
      stimuli in pure upright blocks. This interference effect is a result of
      maintaining readiness for mental rotation. In two experiments we investigated
      previous evidence that these costs depend upon distinct sub-processes for
      children and for adults. In Experiment 1, the maintaining costs turned out to be
      independent of the visual quality of the stimulus for adults but not so for
      children. Experiment 2 revealed that the maintaining costs were greatly reduced
      for adults when they performed mental rotation as a go-no-go task, but not so for
      children. Taken together, both experiments provide evidence that whereas
      perceptual processes seem to be important for school-age children to maintain
      readiness for mental rotation, response selection is relevant for adults.

PMID- 17210114
TI  - Hydrolysis characterization of phospholipid monolayers catalyzed by different
      phospholipases at the air-water interface.
AB  - Combination of some newly developed microscopic and spectroscopic techniques with
      conventional Langmuir monolayer method can provide more quantitative information
      with the molecular orientation and reorganization process of spread amphiphilic
      molecules at the air/water interface. These techniques are extended to
      investigate the hydrolysis process of spreading lipid monolayer catalyzed by
      different enzymes, phospholipases A2, C and D, respectively. Synchrotron X-ray
      diffraction and infrared reflection absorption spectroscopy are able directly to
      give the structural information of the assembled monolayer, interfacial activity
      of amphiphiles and their components at the interface. Microscopic technique such
      as Brewster angle microscopy (BAM), fluorescence microscopy (FM) can be used to
      trace the morphological changes dynamically as the spreading lipid monolayer is
      hydrolyzed at the air/water interface. We summary here some latest progress in
      this filed and give a brief review over the hydrolysis features of phospholipid
      monolayer catalyzed by different enzymes. It is attempted to establish a model of
      membrane hydrolysis process in order to better understand the mechanism of
      membrane metabolism and signal transduction in a living system.

PMID- 17210115
TI  - The effects of single and repeated bouts of soccer-specific exercise on salivary
      IgA.
AB  - OBJECTIVE: Athletes frequently train with a short time recovery between sessions.
      The present aim was to establish how salivary IgA is altered following two soccer
      specific intermittent exercise bouts performed on the same day. DESIGN: Ten males
      participated in two experimental trials (single session, double session) 1 week
      apart, in a counterbalanced design. One trial entailed afternoon exercise only
      (PMEX), in which participants completed soccer-specific intermittent exercise
      starting at 14:30h. On the other occasion, participants performed two bouts of
      exercise [starting at 10:30h (AMEX(1)) and at 14:30h (PMEX(2))]. Timed
      unstimulated saliva samples were collected before and immediately after exercise.
      RESULTS: Mean salivary IgA levels increased significantly immediately post
      exercise in the single afternoon trial (PMEX). Performance of a second soccer
      specific exercise bout in 1 day elicited an increase in heart rate and perceived
      exertion, compared with the single session, but did not appear to suppress
      salivary IgA outcomes. Performing soccer-specific exercise at these different
      times of day did not affect the salivary IgA concentration and secretion rate or
      salivary cortisol in the short term. CONCLUSIONS: These findings suggest that,
      two 90-min exercise sessions performed at a moderate intensity with a 2.25h rest
      in between do not necessarily have adverse effects on salivary IgA levels.

PMID- 17210116
TI  - Tongue deformation, jaw movement and muscle activity during mastication in pigs.
AB  - This study was undertaken to address the lack of information about tongue
      functional deformation in relation to jaw movement and muscle activity.
      Dimensional changes in tongue anterior and base widths, body length and base
      thickness were measured using six ultrasonic crystals implanted into the tongue
      in eight Yucatan minipigs. Jaw movements were captured on videotape and
      digitized, and electromyography (EMG) of tongue intrinsic (verticalis/transversus
      [V/T], superior and inferior longitudinalis [SL, IL]), extrinsic (genioglossus
      and styloglossus [GG, SG) and jaw (masseter and digastricus [MA, DI]) muscles
      were recorded. Signals from these three sources were synchronized. Tongue
      dimensions showed stereotyped and rhythmic changes during chewing cycles, with
      the largest changes in the body length and base thickness of the contralateral
      (non-working) side. The anterior tongue widened during jaw opening while the
      tongue base widened and thickened during jaw closing. The body lengthening
      accompanied base widening and ended at early power stroke, while base thickening
      lasted through most of the power stroke. Significant associations were found
      between changes of anterior width, body length and base thickness and integrated
      EMGs of VT, SL, SG, GG, MA and DI, but not IL. Thus, majority of tongue
      dimensional expansions occur during jaw closing. Intrinsic tongue muscle
      activities are not correlated more with tongue dimensional changes than are
      extrinsic tongue and jaw muscle activities.

PMID- 17210118
TI  - Na(v)1.7 sodium channel expression in human lingual nerve neuromas.
AB  - OBJECTIVE: Peripheral branches of the trigeminal nerve are often damaged during
      the removal of lower third molar teeth, and a small proportion of patients who
      sustain an injury develop persistent chronic pain. The cause of the pain is not
      clear and there are no satisfactory methods of treatment. The aim of the present
      study was to examine the expression of the sodium channel subtype Na(v)1.7 in
      damaged human lingual nerves, and to identify any association between Na(v)1.7
      expression and reported symptoms of dysaesthesia. METHODS: Eleven neuromas-in
      continuity (NICs) and 11 nerve-end neuromas (NENs) were studied, and were all
      obtained at the time of surgical repair of the damaged lingual nerve. Specimens
      were categorised as being obtained from patients with symptoms or without
      symptoms, according to the degree of pain, tingling or discomfort that had been
      experienced. The tissue was prepared and processed for indirect
      immunofluorescence, and image analysis was used to quantify the percentage area
      of PGP 9.5-labelled tissue that also contained Na(v)1.7. RESULTS: The results
      demonstrated that sodium channel Na(v)1.7 was expressed in human lingual nerve
      neuromas. There was no direct relationship between the level of expression of
      Na(v)1.7 and the patients' symptoms of dysaesthesia. However, in NICs there was
      found to be an inverse correlation between Na(v)1.7 and macrophage expression,
      and in symptomatic NICs a direct correlation was found between Na(v)1.7
      expression and axonal apposition. CONCLUSIONS: These data suggest that Na(v)1.7
      expression alone does not play a primary role in initiating the painful symptoms
      of dysaesthesia. The development of neuropathic pain may involve complex
      interactions including changes in ultrastructure and ion channel density.

PMID- 17210117
TI  - Immunohistochemical characterization of slow and fast myosin heavy chain
      composition of muscle fibres in the styloglossus muscle of the human and macaque
      (Macaca rhesus).
AB  - OBJECTIVE: Muscle fibre contractile diversity is thought to be increased by the
      hybridization of multiple myosin heavy chain (MHC) isoforms in single muscle
      fibres. Reports of hybrid fibres composed of MHCI and MHCII isoforms in human,
      but not macaque, tongue muscles, suggest a human adaptation for increased tongue
      muscle contractile diversity. Here we test whether hybrid fibres composed of MHCI
      and MHCII are unique to human tongue muscles or are present as well in the
      macaque. METHODS: MHC composition of the macaque and human styloglossus was
      characterized with antibodies that allowed identification of three muscle fibre
      phenotypes, a slow phenotype composed of MHCI, a fast phenotype composed of MHCII
      and a hybrid phenotype composed of MHCI and MHCII. RESULTS: The fast phenotype
      constitutes 68.5% of fibres in the macaque and 43.4% of fibres in the human
      (P<0.0001). The slow phenotype constitutes 20.2% of fibres in the macaque and
      39.3% of fibres in the human (P<0.0001). The hybrid phenotype constitutes 11.2%
      of fibres in the macaque and 17.3% of fibres in the human (P=0.0002). Macaques
      and humans do not differ in fiber size (cross-sectional area, diameter). However,
      measures of fibre size differ by phenotype such that fast>hybrid>slow (P<0.05).
      CONCLUSION: These data demonstrate differences in the relative percent of muscle
      fibre phenotypes in the macaque and human styloglossus but also demonstrate that
      all three phenotypes are present in both species. These data suggest a similar
      range of mechanical properties in styloglossus muscle fibres of the macaque and
      human.

PMID- 17210119
TI  - Structural investigations on native collagen type I fibrils using AFM.
AB  - This study was carried out to determine the elastic properties of single collagen
      type I fibrils with the use of atomic force microscopy (AFM). Native collagen
      fibrils were formed by self-assembly in vitro characterized with the AFM. To
      confirm the inner assembly of the collagen fibrils, the AFM was used as a
      microdissection tool. Native collagen type I fibrils were dissected and the inner
      core uncovered. To determine the elastic properties of collagen fibrils the tip
      of the AFM was used as a nanoindentor by recording force-displacement curves.
      Measurements were done on the outer shell and in the core of the fibril. The
      structural investigations revealed the banding of the shell also in the core of
      native collagen fibrils. Nanoindentation experiments showed the same Young's
      modulus on the shell as well as in the core of the investigated native collagen
      fibrils. In addition, the measurements indicate a higher adhesion in the core of
      the collagen fibrils compared to the shell.

PMID- 17210121
TI  - An ultraviolet photoacoustic spectroscopy study of the interaction between Lys49
      phospholipase A2 and amphiphilic molecules.
AB  - We have used near ultraviolet photoacoustic spectroscopy (PAS) over the
      wavelength range 240-320 nm to investigate the complex formed between the
      homodimeric bothropstoxin-I, a lysine-49-phospholipase A2 from the venom of
      Bothrops jararacussu (BthTx-I), with the anionic amphiphile sodium dodecyl
      sulfate (SDS). At molar ratios>10, the complex developed a significant light
      scatter, accompanied by a decrease in the intrinsic tryptophan fluorescence
      intensity emission (ITFE) of the protein, and an increase in the near UV-PAS
      signal. Difference PAS spectroscopy at SDS/BthTx-I ratios<8 were limited to the
      region 280-290 nm, suggesting initial SDS binding to the tryptophan 77 located at
      the dimer interface. At SDS/BthTx-I ratios>10, the intensity between 260 and 320
      nm increases demonstrating that the more widespread tyrosine and phenylalanine
      residues contribute to the SDS/BthTx-I interaction. PAS signal phase changes at
      wavelengths specific for each aromatic residue suggest that the Trp77 becomes
      more buried on SDS binding, and that protein structural changes and dehydration
      may alter the microenvironments of Tyr and Phe residues. These results
      demonstrate the potential of near UV-PAS for the investigation of membrane
      proteins/detergent complexes in which light scatter is significant.

PMID- 17210120
TI  - Nitric oxide stimulates insulin gene transcription in pancreatic beta-cells.
AB  - Recent studies have identified a positive role for nitric oxide (NO) in the
      regulation of pancreatic beta-cell function. The aim of this study was to
      determine the effects of short-term exposure to NO on beta-cell gene expression
      and the activity of the transcription factor PDX-1. NO stimulated the activity of
      the insulin gene promoter in Min6 beta-cells and endogenous insulin mRNA levels
      in both Min6 and isolated islets of Langerhans. Addition of wortmannin prior to
      NO stimulation blocked the observed increases in insulin gene promoter activity.
      Although NO addition stimulated the phosphorylation of p38, inhibition by
      SB203580 did not block the effect of NO on the insulin gene promoter. NO addition
      also stimulated both the nuclear accumulation and the DNA binding activity of PDX
      1. This study has shown that over 24h, NO stimulates insulin gene expression, PI
      3-kinase activity and the activity of the critical beta-cell transcription factor
      PDX-1.

PMID- 17210122
TI  - Increased SOCS6 stability with PMA requires its N-terminal region and the Erk
      pathway via Pkcdelta activation.
AB  - We investigated stability of the ectopically expressed the SOCS6 protein in
      HEK293T cells with PMA, which activates protein kinase C (PKC). The treatment of
      PMA could largely increase SOCS6 stability in HEK293T cells. But, we did not
      observe increased protein levels of SOCS3 or Erk1 with PMA. This result suggests
      that the increased stability of SOCS6 with PMA did not generally occur in other
      proteins. The stability of SOCS6 depended on the N-terminal region containing an
      unidentified domain. We then studied the role of signal pathways in SOCS6
      stability with PMA. We found that both Erk and Pkcdelta activation were required
      for the increased SOCS6 stability by PMA. The Erk activation by PMA appeared to
      be downstream from the Pkcdelta activation. The increased SOCS6 stability and Erk
      activation by PMA were both conserved in another cell line, MCF7. In addition, we
      demonstrated that PMA, insulin, and PDGF increased both the stability of
      endogenous-expressed SOCS6 and Erk activation in MDA-MB231 cells. These
      observations suggest that Erk activation may be correlated in the cells with high
      expression of SOCS6.

PMID- 17210123
TI  - Inhibition of HIV-1 infection by synthetic peptides derived CCR5 fragments.
AB  - HIV-1 infection requires interaction of viral envelope protein gp160 with CD4 and
      a chemokine receptor, CCR5 or CXCR4 as entry coreceptor. We designed HIV
      inhibitory peptides targeted to CCR5 using a novel computer program (ANTIS),
      which searched all possible sense-antisense amino acid pairs between proteins.
      Seven AHBs were found in CCR5 receptor. All AHB peptides were synthesized and
      tested for their ability to prevent HIV-1 infection to human T cells. A peptide
      fragment (LC5) which is a part of the CCR5 receptor corresponding to the loop
      between the fifth and sixth transmembrane regions (amino acids 222-240) proved to
      inhibit HIV-1IIIB infection of MT-4 cells. Interaction of these antisense
      peptides could be involved in sustaining HIV-1 infectivity. LC5 effectively
      indicated dose-dependent manner, and the suppression was enhanced additively by
      T20 peptide, which inhibits infection in vitro by disrupting the gp41
      conformational changes necessary for membrane fusion. Thus, these results
      indicate that CCR5-derived AHB peptides could provide a useful tool to define the
      mechanism(s) of HIV infection, and may provide insight which will contribute to
      the development of an anti-HIV-1 reagent.

PMID- 17210124
TI  - MMP-2 inhibition reduces renal macrophage infiltration with increased fibrosis in
      UUO.
AB  - We examined the role of matrix metalloproteinase-2 (MMP-2) in renal fibrosis and
      its effect on interstitial macrophage infiltration in a mouse model of unilateral
      ureteral obstruction (UUO). TISAM, a selective inhibitor of MMP-2, was
      administered during early stage (day -2 to 4; protocol A) and late stage (day 7
      to 13; protocol B) after UUO. Treatment with TISAM accelerated fibrosis both at
      day 5 (A) and at day 14 (B). The degree of macrophage infiltration was decreased
      by the treatment with TISAM at day 14, but not at day 5. In vitro macrophage
      migration assay showed a greater migration to renal tissue of control UUO kidney
      (day 14) than to TISAM-treated kidney, which was suppressed by preincubating
      macrophages with RGDS, a fibronectin degradation peptide. These results suggest
      that MMP-2 acts to accelerate macrophage infiltration in the late stage of UUO,
      possibly by degrading extracellular matrix components.

PMID- 17210125
TI  - Methamphetamine downregulates peroxiredoxins in rat pheochromocytoma cells.
AB  - Methamphetamine (METH) is an abusive psychostimulant that induces neuronal cell
      death/degeneration in experimental animals and humans. METH-induced apoptosis in
      rat pheochromocytoma cells was utilized to study the neurotoxic mechanism. During
      METH intoxication, we found that peroxiredoxins and thioredoxins/thioredoxin
      reductases (peroxiredoxin reducing systems) which are known to prevent oxidative
      stress and apoptosis were differentially downregulated and upregulated,
      respectively. We also found not only the free radicals but also the oxidative
      forms of peroxiredoxin and thioredoxin were increased, indicating the dysfunction
      of these enzymes. Thus, METH-induced differential regulation and oxidation of
      peroxiredoxins and thioredoxin may be an important mechanism for apoptosis.

PMID- 17210126
TI  - Comparison of histone modifications in in vivo and in vitro fertilization mouse
      embryos.
AB  - Histone modifications are thought to play important roles in various cellular
      functions. In this article, the distribution patterns of acetylation on histone
      H4, methylation on histone H3 lysine 9, and phosphorylation on histone H3 serine
      10 were examined in in vivo and in vitro fertilization (IVF) preimplantation
      mouse embryos by using indirect immunofluorescence and scanning confocal
      microscopy. We desired to know whether the IVF, which has been widely used as a
      routine assisted reproductive technology in animal and human, was safe at the
      epigenetic level. As results, we found that there was no difference in these
      histone modification patterns in in vivo and IVF mouse embryos from zygote to
      blastocyst stage. Moreover, these histone modifications had different
      distributions at all examined stages, but they were consistent with the mouse
      embryo developmental stages.

PMID- 17210127
TI  - Assay and characterization of a strong promoter element from B. subtilis.
AB  - A new strong promoter fragment isolated from Bacillus subtilis was identified and
      characterized. Using the heat stable beta-galactosidase as reporter, the promoter
      fragment exhibited high expression strength both in Escherichia coli and B.
      subtilis. The typical prokaryotic promoter conservation regions were found in the
      promoter fragment and the putative promoter was identified as the control element
      of yxiE gene via sequencing assay and predication of promoter. To further verify
      and characterize the cloned strong promoter, the putative promoter was sub-cloned
      and the beta-Gal directed by the promoters was high-level expressed both in E.
      coli and B. subtilis. By means of the isolated promoter, an efficient expression
      system was developed in B. subtilis and the benefit and usefulness was
      demonstrated through expression of three heterologous and homogenous proteins.
      Thus, we identified a newly strong promoter of B. subtilis and provided a robust
      expression system for genetic engineering of B. subtilis.

PMID- 17210128
TI  - In vivo treatment by diallyl disulfide increases histone acetylation in rat
      colonocytes.
AB  - Diallyl disulfide (DADS) is an organosulfur compound from garlic which exhibits
      various anticarcinogenic properties including inhibition of tumor cell
      proliferation. DADS antiproliferative effects were previously associated with an
      increase in histone acetylation in two human tumor colon cell lines, suggesting
      that DADS-induced histone hyperacetylation could be one of the mechanisms
      involved in its protective properties on colon carcinogenesis. The effects of
      DADS on histone H4 and H3 acetylation levels were investigated in vivo in
      colonocytes isolated from non-tumoral rat. Administrated by intracaecal perfusion
      or gavage, DADS increases histone H4 and H3 acetylation in colonocytes. Moreover,
      data generated using cDNA expression arrays suggest that DADS could modulate the
      expression of a subset of genes. These results suggest the involvement of histone
      acetylation in modulation of gene expression by DADS in normal rat colonocytes,
      which might play a role in its biological effects as well as in its
      anticarcinogenic properties in vivo.

PMID- 17210129
TI  - Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice
      carrying a Toll-like receptor 4 mutation.
AB  - Obese adipose tissue is characterized by increased infiltration of macrophages,
      suggesting that they might represent an important source of inflammation. We have
      provided in vitro evidence that saturated fatty acids, which are released from
      hypertrophied adipocytes via the macrophage-induced adipocyte lipolysis, serve as
      a naturally occurring ligand for Toll-like receptor 4 (TLR4) to induce the
      inflammatory changes in macrophages. Here we show the attenuation of adipose
      tissue inflammation in C3H/HeJ mice carrying a functional mutation in the TLR4
      gene relative to control C3H/HeN mice during a 16-week high-fat diet. We also
      find that adiponectin mRNA expression is significantly reduced by co-culture of
      hypertrophied 3T3-L1 adipocytes and C3H/HeN peritoneal macrophages, which is
      reversed, when co-cultured with C3H/HeJ peritoneal macrophages. This study
      provides in vivo evidence that TLR4 plays a role in obesity-related adipose
      tissue inflammation and thus helps to identify the therapeutic targets that may
      reduce obesity-induced inflammation and the metabolic syndrome.

PMID- 17210130
TI  - Physical dissection of the CCAAT/enhancer-binding protein alpha in regulating the
      mouse amelogenin gene.
AB  - The amelogenin gene is tightly regulated at the temporal and spatial level in
      accord with the developmental requirement for tooth formation. Previous studies
      have shown that CCAAT/enhancer-binding protein alpha (C/EBPalpha) is a
      transactivator of the mouse X-chromosomal amelogenin gene. C/EBPalpha contains
      four highly conserved regions (CR) named CR1, CR2, CR3, and CR4. Transient
      transfection assays showed that CR2 in isolation had an exceptional capacity to
      enhance transcription from the 2.3 kb mouse amelogenin promoter. The remaining
      conserved regions of C/EBPalpha, either in isolation or in selected combinations,
      were less effective in amelogenin transactivation than the full length
      C/EBPalpha. Msx2 has previously been shown to antagonize C/EBPalpha through
      protein-protein interactions with C/EBPalpha, and the carboxyl-terminus of Msx2
      is required for protein-protein interactions. Co-immunoprecipitation analyses
      identified that the carboxyl-terminal domain (residues 218-359) of C/EBPalpha is
      required for the C/EBPalpha-Msx2 protein-protein interactions.

PMID- 17210131
TI  - Mtf-1 lymphoma-susceptibility locus affects retention of large thymocytes with
      high ROS levels in mice after gamma-irradiation.
AB  - Mouse strains exhibit different susceptibilities to gamma-ray-induced thymic
      lymphomas. Our previous study identified Mtf-1 (metal responsive transcription
      factor-1) as a candidate susceptibility gene, which is involved in the radiation
      induced signaling pathway that regulates the cellular reactive oxygen species
      (ROS). To reveal the mechanism for the increased susceptibility conferred by Mtf
      1 locus, we examined early effects of gamma-ray on ROS levels in vivo and its
      difference between Mtf-1 susceptible and resistant congenic mice. Here, we show
      the detection of clonally growing thymocytes at 4 weeks after irradiation,
      indicating the start of clonal expansion at a very early stage. We also show that
      large thymocytes with higher ROS levels and a proliferation capacity were more
      numerous in the Mtf-1 susceptible mice than the resistant mice when examined at 7
      days after irradiation, although such tendency was not found in mice lacking one
      allele of Bcl11b tumor suppressor gene. This high retention of the large
      thymocytes, at a high risk for ROS-induced mutation, is a compensatory
      proliferation and regeneration response to depletion of the thymocytes after
      irradiation and the response is likely to augment the development of prelymphoma
      cells leading to thymic lymphomas.

PMID- 17210132
TI  - SEPS1 protects RAW264.7 cells from pharmacological ER stress agent-induced
      apoptosis.
AB  - Selenoprotein S (SEPS1) is a novel endoplasmic reticulum (ER) resident protein
      and it is known to play an important role in production of inflammatory
      cytokines. Here, we show evidence that SEPS1 is stimulated by pharmacological ER
      stress agents in RAW264.7 macrophages as well as other cell types. Overexpression
      studies reveal a protective action of SEPS1 in macrophages against ER stress
      induced cytotoxicity and apoptosis, resulting in promoting cell survival during
      ER stress. The protective action of SEPS1 is largely dependent on ER stress
      mediated cell death signal with less effect on non-ER stress component cell death
      signals. Conversely, suppression of SEPS1 in macrophages results in sensitization
      of cells to ER stress-induced cell death. These findings suggest that SEPS1 could
      be a new ER stress-dependent survival factor that protects macrophage against ER
      stress-induced cellular dysfunction.

PMID- 17210133
TI  - Lipoic acid stimulates cAMP production in T lymphocytes and NK cells.
AB  - The anti-oxidant lipoic acid (LA) potently suppresses clinical and pathologic
      disease in the animal model of multiple sclerosis, experimental autoimmune
      encephalomyelitis, by inhibiting the migration of pathogenic T cells to the
      spinal cord. The mechanism by which this occurs is largely unknown. In this
      report we demonstrate that LA induces increases in cyclic AMP, a known
      immunosuppressant, in human T cells. The increase in cAMP is associated with
      increased adenylyl cyclase activity and is partially blocked by prostanoid
      receptor antagonists. We present evidence that LA also stimulates cAMP production
      in natural killer (NK) cells. This novel mechanism of action is highly relevant
      to the immunomodulatory effects of LA and provides further support for the study
      of LA as a therapeutic agent for multiple sclerosis and other autoimmune
      diseases.

PMID- 17210134
TI  - Genotype and childhood sexual trauma moderate neurocognitive performance: a
      possible role for brain-derived neurotrophic factor and apolipoprotein E
      variants.
AB  - BACKGROUND: Limited success in the identification of genetic variants
      underpinning psychiatric illness has prompted attempts to elucidate gene
      environment interactions and illness-associated endophenotypes. Here we measured
      childhood sexual abuse, a potential environmental risk factor, and verbal and
      visual recall and recognition memory, a possible illness-associated endophenotype
      in a cohort of bipolar disorder (BPD) subjects and their relatives. We predicted
      that memory would be affected by sexual trauma and that a number of functional
      polymorphisms previously implicated in BPD and cognition would moderate the
      effect of psychological trauma on memory. METHODS: A cohort of 350 individuals
      from 47 BPD families was recruited, tested with a neuropsychological battery, and
      given the Childhood Trauma Questionnaire (CTQ). Eleven different genetic variants
      previously found to be relevant to BPD or memory dysfunction were typed. RESULTS:
      As predicted, scores on the sexual abuse scale of the CTQ were negatively
      associated with memory performance. Furthermore, the low-activity Met allele of
      the brain-derived neurotrophic factor (BDNF) gene and the epsilon4 allele of the
      apolipoprotein E gene interacted with sexual abuse scores to result in reduced
      memory test performance. CONCLUSIONS: Apolipoprotein E and BDNF exert a
      neurotrophic effect in response to cellular injury. Their possible moderation of
      the association between sexual abuse and memory performance might indicate that
      there is some degree of overlap in the pathophysiological mechanisms by which
      psychological and physical trauma impact brain function. The finding of an
      environmental effect on memory performance and a gene-environment interaction on
      this hypothetical endophenotype of BPD illustrates the difficulty of identifying
      genetically and phenotypically simple intermediate traits for molecular genetic
      studies.

PMID- 17210135
TI  - Reduction in occipital cortex gamma-aminobutyric acid concentrations in
      medication-free recovered unipolar depressed and bipolar subjects.
AB  - BACKGROUND: Studies using proton magnetic resonance spectroscopy (MRS) have
      indicated that unmedicated, acutely depressed patients have decreased levels of
      gamma-aminobutyric acid (GABA) in occipital cortex. Cortical levels of glutamate
      (Glu) may be increased, although these data are less consistent. The aim of this
      study was to use MRS to determine whether changes in GABA and Glu levels were
      present in patients with mood disorders who had recovered and were no longer
      taking medication. METHODS: An [1H]-MRS was used to measure levels of GABA, of
      the combined concentration of Glu and glutamine (Gln), and of N-acetylaspartate
      (NAA) in occipital cortex in medication-free, fully recovered subjects with a
      history of recurrent unipolar depression (n = 15), bipolar disorder (n = 16), and
      a group of healthy controls (n = 18). RESULTS: Occipital levels of GABA and NAA
      were significantly lower in recovered depressed and bipolar subjects than in
      healthy controls, whereas Glu +Gln concentrations were higher. CONCLUSIONS: Our
      data suggest that recovered unmedicated subjects with a history of mood disorder
      have changes in cortical concentrations of GABA, NAA, and Glu +Gln. These
      biochemical abnormalities may be markers of a trait vulnerability to mood
      disorder, rather than neurochemical correlates of an abnormal mood state.

PMID- 17210136
TI  - Amygdala and orbitofrontal reactivity to social threat in individuals with
      impulsive aggression.
AB  - BACKGROUND: Converging evidence from animal and human lesion studies implicates
      the amygdala and orbitofrontal cortex (OFC) in emotional regulation and
      aggressive behavior. However, it remains unknown if functional deficits exist in
      these specific brain regions in clinical populations in which the cardinal
      symptom is impulsive aggression. We have previously shown that subjects diagnosed
      with intermittent explosive disorder (IED), a psychiatric disorder characterized
      by reactive aggressive behavior, perform poorly on facial emotion recognition
      tasks. In this study we employed a social-emotional probe of amygdala-OFC
      function in individuals with impulsive aggression. METHODS: Ten unmedicated
      subjects with IED and 10 healthy, matched comparison subjects (HC) underwent
      functional magnetic resonance imaging while viewing blocks of emotionally salient
      faces. We compared amygdala and OFC reactivity to faces between IED and HC
      subjects, and examined the relationship between the extent of activation in these
      regions and extent of prior history of aggressive behavior. RESULTS: Relative to
      controls, individuals with IED exhibited exaggerated amygdala reactivity and
      diminished OFC activation to faces expressing anger. Extent of amygdala and OFC
      activation to angry faces were differentially related to prior aggressive
      behavior across subjects. Unlike controls, aggressive subjects failed to
      demonstrate amygdala-OFC coupling during responses to angry faces. CONCLUSIONS:
      These findings provide evidence of amygdala-OFC dysfunction in response to an
      ecologically-valid social threat signal (processing angry faces) in individuals
      with a history of impulsive aggressive behavior, and further substantiate a link
      between a dysfunctional cortico-limbic network and aggression.

PMID- 17210137
TI  - Risperidone and cognitive function in children with disruptive behavior
      disorders.
AB  - BACKGROUND: Effects of risperidone on cognitive function in children with
      disruptive behavior disorders (DBDs) and subaverage intelligence quotient (IQ)
      were assessed. METHODS: Data from two 6-week, double-blind, placebo-controlled
      studies (n = 228) were combined, as were three 1-year, open-label studies (n =
      688). Patients with DBDs and subaverage IQ, 5 to14 years, received placebo or
      risperidone .02 to .06 mg/kg/day. Cognitive measures included the Continuous
      Performance Task (CPT) and Verbal Learning Test for Children (VLT-C). Efficacy
      was assessed using the Nisonger Child Behavior Rating Form (NCBRF). Adverse
      events were collected via spontaneous report; sedation was assessed using visual
      analog scale. RESULTS: Improvements on the NCBRF Conduct Problem subscale were
      significantly greater for risperidone- versus placebo-treated patients (-15.8 vs.
      -6.4, p < .0001) in short-term studies; significant reductions were observed in
      long-term studies (-16.3, p < .0001). No overall decline and some significant
      improvement in attention (CPT) and memory (VLT-C) were noted regardless of
      treatment in short-term studies. VLT-C improved significantly (p < .0001) for
      both groups, with no difference between treatment groups. Improvements in memory
      (VLT-C) and attention (CPT) were noted in long-term studies. Somnolence/sedation
      did not affect cognitive function. CONCLUSIONS: Cognitive function was not
      altered by risperidone in short-term studies and was maintained or improved with
      one year of treatment in children with DBDs and subaverage IQ, potentially
      representing age-appropriate gains.

PMID- 17210138
TI  - Impact of emotional salience on episodic memory in attention
      deficit/hyperactivity disorder: a functional magnetic resonance imaging study.
AB  - BACKGROUND: Patients with attention-deficit/hyperactivity disorder (ADHD) show
      episodic memory deficits especially in complex memory tasks. We investigated the
      neural correlates of memory formation in ADHD and their modulation by stimulus
      salience. METHODS: We recorded event-related functional magnetic resonance
      imaging during an episodic memory paradigm with neutral and emotional pictures in
      12 male ADHD subjects and 12 healthy adolescents. RESULTS: Emotional salience did
      significantly augment memory performance in ADHD patients. Successful encoding of
      neutral pictures was associated with activation of the anterior cingulate cortex
      (ACC) in healthy adolescents but with activation of the superior parietal lobe
      (SPL) and precuneus in ADHD patients. Successful encoding of emotional pictures
      was associated with prefrontal and inferior temporal cortex activation in both
      groups. Healthy adolescents, moreover, showed deactivation in the inferior
      parietal lobe. CONCLUSIONS: From a pathophysiological point of view, the most
      striking functional differences between healthy adolescents and ADHD patients
      were in the ACC and SPL. We suggest that increased SPL activation in ADHD
      reflected attentional compensation for low ACC activation during the encoding of
      neutral pictures. The higher salience of emotional stimuli, in contrast,
      regulated the interplay between ACC and SPL in conjunction with improving memory
      to the level of healthy adolescents.

PMID- 17210139
TI  - TIMP-1 abolishes MMP-9-dependent long-lasting long-term potentiation in the
      prefrontal cortex.
AB  - BACKGROUND: Understanding of the molecular mechanisms of prefrontal cortex (PFC)
      plasticity is important for developing new treatment strategies for mental
      disorders such as depression and schizophrenia. Long-term potentiation (LTP) is a
      valid model for synaptic plasticity. The extracellular proteolytic system
      composed of matrix metalloproteinases (MMPs) and their endogenous tissue
      inhibitors (TIMPs) has recently been shown to play major role in the hippocampal
      plasticity. METHODS: We tested whether induction of hippocampal-prefrontal LTP
      results in accumulation of tissue inhibitor of MMP-1, TIMP-1 mRNA, in the PFC of
      rats and whether adenovirally driven overexpression of TIMP-1 affects LTP.
      Additional study of slices was done with a specific MMP-9 inhibitor. RESULTS: The
      TIMP-1 is induced in the rat medial PFC by stimuli evoking late LTP; its
      overexpression blocks the gelatinolytic activity of the MMP family; its
      overexpression before tetanization blocks late LTP in vivo; and MMP-9 inhibitor
      prevents late LTP in vitro. CONCLUSIONS: We suggest a novel extracellular
      mechanism of late LTP in the PFC, engaging TIMP-1-controlled proteolysis as an
      element of information integration. Our results may also be meaningful to an
      understanding of mental diseases and development of new treatment strategies that
      are based on extracellular mechanisms of synaptic plasticity.

PMID- 17210140
TI  - Depression, C-reactive protein and two-year major adverse cardiac events in men
      after acute coronary syndromes.
AB  - BACKGROUND: We investigated the impact of depression and inflammatory markers,
      assessed 2 months after acute coronary syndrome (ACS), on major adverse cardiac
      events over 2 years (MACEs; cardiac death, survived myocardial infarction,
      survived cardiac arrest, and nonelective revascularization). METHODS: Depression
      symptoms (Beck Depression Inventory-II; BDI-II), major depression, C-reactive
      protein (CRP), interleukin-6, and soluble intercellular adhesion molecule were
      assessed in 741 ACS patients (including 602 men). RESULTS: Some 102 (78 men)
      experienced at least one MACE. Beck Depression Inventory-II scores of > or =14
      predicted MACEs (p = .007). The increase in risk was marked in men (hazard ratio
      [HR] = 1.96, 95% confidence interval [CI] = 1.24-3.09, p = .004), with little
      evidence of a relationship in women (p = .85). Subsequent analyses were limited
      to men. Results were similar after covariate adjustment (HR = 1.72, 95% CI = 1.07
      2.77, p = .024). C-reactive protein levels were also associated with increased
      MACE risk (adjusted HR for CRP > or = 2.0 mg/L = 1.67, 95% CI = 1.07-2.62, p =
      .025). C-reactive protein levels and BDI-II scores interacted in predicting
      MACEs. Men with both BDI-II scores of > or =14 and CRP of > or =2.0 mg/L
      experienced an increase in risk similar to those with only one of these factors.
      CONCLUSIONS: In men assessed 2 months after ACS, depression and CRP are
      overlapping prognostic risks. Patients with either risk may benefit from similar
      therapies.

PMID- 17210141
TI  - Novel 5-HTTLPR allele associates with higher serotonin transporter binding in
      putamen: a [(11)C] DASB positron emission tomography study.
AB  - BACKGROUND: The serotonin transporter (5-HTT)-linked polymorphic region (5
      HTTLPR) has two frequent alleles, designated long (L), and short (S). The S
      allele is associated with lower levels of 5-HTT mRNA and lower 5-HTT expression
      in human cell lines. A functional single nucleotide variant was detected within
      L, designated L(A) and L(G). Only L(A) is associated with high levels of in vitro
      5-HTT expression, whereas L(G) is low expressing and more similar to S. We
      examined the possible influence of the long (A/G) variant on 5-HTT density in the
      living human brain using 3-(11)C-amino-4-(2-dimethylaminomethylphenyl-sulfanyl)
      benzonitrile ([(11)C]DASB) positron emission tomography. METHODS: The 5-HTT
      binding potential (5-HTT BP), an index of 5-HTT density, was found in 43 healthy
      subjects genotyped for 5-HTTLPR long (A/G), and in an ethnically homogenous
      subsample of 30 Caucasian-Canadians. RESULTS: The L(A)/L(A) was associated with
      higher 5-HTT BP in putamen (p = .026, not corrected). This association became
      stronger in the Caucasian subsample (p = .004) and was significant even after
      correcting for multiple comparisons. CONCLUSIONS: The 5-HTTLPR long (A/G)
      polymorphism influences 5-HTT density leading to higher putamen 5-HTT BP in
      healthy L(A)/L(A) carriers of Caucasian ancestry. This finding extends the role
      of this polymorphism from in vitro reports of higher 5-HTT expression with the
      L(A)/L(A) genotype into in vivo brains of healthy human subjects.

PMID- 17210142
TI  - MLC1 polymorphisms are specifically associated with periodic catatonia, a
      subgroup of chronic schizophrenia.
AB  - BACKGROUND: The MLC1, located on chromosome 22q13.33, has been suggested as a
      risk gene for schizophrenia, especially the periodic catatonia subtype. An
      initially identified missense mutation was found to be extremely rare in other
      patient cohorts; however, a recent report again argued for an association of two
      intronic MLC1 single nucleotide polymorphisms (SNPs) with schizophrenia and
      bipolar disorder. METHODS: A case-control study of these polymorphisms as well as
      SNPs in the transcriptional control region of MLC1 was conducted in 212 chronic
      schizophrenic patients, 56 of which suffered from periodic catatonia, 106 bipolar
      patients, and 284 controls. RESULTS: Both intronic and promoter polymorphisms
      were specifically and significantly associated with periodic catatonia but not
      schizophrenia or bipolar disorder in general. A haplotype constructed from all
      polymorphisms was also associated with periodic catatonia. CONCLUSIONS: The MLC1
      variation is associated with periodic catatonia; whether it constitutes a
      susceptibility or a modifier gene has to be determined.

PMID- 17210144
TI  - Successful aging: from phenotype to genotype.
AB  - Despite worldwide interest in the increasing human "healthspan," inadequate
      experimental attention has been dedicated to identifying genetic influences on
      successful aging beyond those that influence longevity alone. Although it is an
      under-studied topic, some promising leads have emerged from the existing genetic
      studies of successful aging. Here we describe the results of a systematic review
      of published family, twin, linkage, and association studies of successful aging
      that evaluated at least one other characteristic of healthy aging in addition to
      longevity. We identified 29 studies that met our criteria. Although
      methodological inconsistencies in sampling and phenotypes were frequent, we found
      evidence for a substantial genetic contribution to successful aging, including
      several specific genes (APOE, GSTT1, IL6, IL10, PON1, and SIRT3) that are
      promising candidates for future molecular genetic research. In addition to
      reviewing this literature, we provide recommendations for advancing our
      understanding of the genetic basis of successful aging.

PMID- 17210143
TI  - Resting-state functional connectivity in major depression: abnormally increased
      contributions from subgenual cingulate cortex and thalamus.
AB  - BACKGROUND: Positron emission tomography (PET) studies of major depression have
      revealed resting-state abnormalities in the prefrontal and cingulate cortices.
      Recently, fMRI has been adapted to examine connectivity within a specific resting
      state neural network--the default-mode network--that includes medial prefrontal
      and anterior cingulate cortices. The goal of this study was to examine resting
      state, default-mode network functional connectivity in subjects with major
      depression and in healthy controls. METHODS: Twenty-eight subjects with major
      depression and 20 healthy controls underwent 5-min fMRI scans while resting
      quietly. Independent component analysis was used to isolate the default-mode
      network in each subject. Group maps of the default-mode network were compared. A
      within-group analysis was performed in the depressed group to explore effects of
      depression refractoriness on functional connectivity. RESULTS: Resting-state
      subgenual cingulate and thalamic functional connectivity with the default-mode
      network were significantly greater in the depressed subjects. Within the
      depressed group, the length of the current depressive episode correlated
      positively with functional connectivity in the subgenual cingulate. CONCLUSIONS:
      This is the first study to explore default-mode functional connectivity in major
      depression. The findings provide cross-modality confirmation of PET studies
      demonstrating increased thalamic and subgenual cingulate activity in major
      depression. Further, the within-subject connectivity analysis employed here
      brings these previously isolated regions of hypermetabolism into the context of a
      disordered neural network. The correlation between refractoriness and subgenual
      cingulate functional connectivity within the network suggests that a
      quantitative, resting-state fMRI measure could be used to guide therapy in
      individual subjects.

PMID- 17210146
TI  - Oculomotor plasticity: are mechanisms of adaptation for reactive and voluntary
      saccades separate?
AB  - Saccadic eye movements are permanently controlled and their accuracy maintained
      by adaptive mechanisms that compensate for physiological or pathological
      perturbations. In contrast to the adaptation of reactive saccades (RS) which are
      automatically triggered by the sudden appearance of a single target, little is
      known about the adaptation of voluntary saccades which allow us to intentionally
      scan our environment in nearly all our daily activities. In this study, we
      addressed this issue in human subjects by determining the properties of
      adaptation of scanning voluntary saccades (SVS) and comparing these features to
      those of RS. We also tested the reciprocal transfers of adaptation between the
      two saccade types. Our results revealed that SVS and RS adaptations disclosed
      similar adaptation fields, time course and recovery levels, with only a slightly
      lower after-effect for SVS. Moreover, RS and SVS main sequences both remained
      unaffected after adaptation. Finally and quite unexpectedly, the pattern of
      adaptation transfers was asymmetrical, with a much stronger transfer from SVS to
      RS (79%) than in the reverse direction (22%). These data demonstrate that
      adaptations of RS and SVS share several behavioural properties but at the same
      time rely on partially distinct processes. Based on these findings, it is
      proposed that adaptations of RS and SVS may involve a neural network including
      both a common site and two separate sites specifically recruited for each saccade
      type.

PMID- 17210145
TI  - An evaluation of distinct volumetric and functional MRI contributions toward
      understanding age and task performance: a study in the basal ganglia.
AB  - Prior work by our group and others has implicated the basal ganglia as important
      in age-related differences in tasks involving motor response control. The present
      study used structural and functional MRI approaches to analyze this region of
      interest (ROI) toward better understanding the contributions of structural and
      functional MRI measures to understanding age-related and task performance-related
      cognitive differences. Eleven healthy elders were compared with 11 healthy
      younger adults while they completed the "go" portion of a complex Go/No-go task.
      Separate ROI's in the bilateral caudate (C) and putamen/globus pallidus (PGp)
      were studied based upon previous findings of age-related functional MRI
      differences in basal ganglia for this portion of the task. Structural volumes and
      functional activation (in percent area under the curve during correct responses)
      were independently extracted for these ROI's. Results showed that age correlated
      with ROI volume in bilateral PGp and C, while multiple task performance measures
      correlated with functional activation in the left PGp. The Go/No-go task measures
      were also significantly correlated with traditional attention and executive
      functioning measures. Importantly, fMRI activation and volumes from each ROI were
      not significantly inter-correlated. These findings suggest that structural and
      functional MRI make unique contributions to the study of performance changes in
      aging.

PMID- 17210147
TI  - Expression of S100 protein and protective effect of arundic acid on the rat brain
      in chronic cerebral hypoperfusion.
AB  - S100 protein is expressed primarily by astroglia in the brain, and accumulates in
      and around the ischemic lesions. Arundic acid, a novel astroglia-modulating
      agent, is neuroprotective in acute cerebral infarction, whereas the protective
      effects remain unknown during chronic cerebral hypoperfusion. Rats undergoing
      chronic cerebral hypoperfusion were subjected to a bilateral ligation of the
      common carotid arteries, and were allowed to survive for 3, 7 and 14 days. The
      animals received a daily intraperitoneal injection of 5.0, 10.0 or 20.0 mg/kg of
      arundic acid, or vehicle, for 14 days. Alternatively, other groups of rats
      received a delayed intraperitoneal injection of 20.0 mg/kg of arundic acid or
      vehicle, which started from 1, 3 or 7 days after ligation and continued to 14
      days. The degree of white matter (WM) lesions and the numerical density of S100
      protein-immunoreactive astroglia were estimated. In the WM of rats with vehicle
      injections, the number of S100 protein-immunoreactive astroglia increased
      significantly after chronic cerebral hypoperfusion as compared to the sham
      operation. A dosage of 10.0 and 20.0 mg/kg of arundic acid suppressed the
      numerical increase in S100 protein-immunoreactive astroglia and the WM lesions.
      These pathological changes were suppressed with delayed treatment up to 7 days in
      terms of astroglial activation, and up to 3 days in terms of the WM lesions. The
      protective effects of arundic acid against WM lesions were demonstrated in a dose
      dependent manner, and even after postischemic treatments. These results suggest
      the potential usefulness of arundic acid in the treatment of cerebrovascular WM
      lesions.

PMID- 17210149
TI  - The crystal structure of the 1:1 inclusion complex of beta-cyclodextrin with
      benzamide.
AB  - The 1:1 inclusion complex of beta-cyclodextrin and benzamide was prepared and
      characterized by single crystal X-ray diffraction, PXRD, TGA, and IR. This
      complex crystallizes in the monoclinic P2(1) space group with unit cell constants
      a=15.4244(16), b=10.1574(11), c=20.557(2)A, beta=110.074(2) degrees ,
      V=3025.1(6)A(3). The guest molecule projects into the beta-cyclodextrin cavity
      from the primary hydroxyl side. The amide group protrudes from the primary
      hydroxyl side and forms hydrogen bonds with the adjacent beta-cyclodextrin
      molecule. There are six crystallized water molecules, which play crucial roles in
      crystal packing.

PMID- 17210148
TI  - The effect of granulocyte-colony stimulating factor in global cerebral ischemia
      in rats.
AB  - Granulocyte-colony stimulating factor (G-CSF) is an endogenous peptide hormone of
      the hematopoietic system that has entered Phase I/II clinical trials for
      treatment of ischemic stroke. Severe intraoperative hypotension can lead to
      global cerebral ischemia and apoptotic neuron loss within the hippocampus. We
      tested G-CSF in a rat model of global cerebral ischemia. Global cerebral ischemia
      was induced in male Sprague-Dawley rats (280-330 g) with the 2-vessel occlusion
      model (hemorrhagic hypotension to a mean arterial pressure of 30-35 mm Hg and
      bilateral common carotid artery occlusion for 8 min). Three groups of animals
      were used: global ischemia without treatment (GI, n=49), global ischemia with G
      CSF treatment (GI+G-CSF, n=42), and sham surgery (Sham, n=26). Rats in the
      treatment group received G-CSF (50 mug/kg, subcutaneously) 12 h before surgery,
      on the day of surgery, and on postoperative Day 1 and were euthanized on Days 2,
      3, and 14. Mild hyperglycemia was observed in all groups. T-maze testing for
      spontaneous alternation demonstrated initial improvement in the G-CSF treatment
      group but no long-term benefit. Measurement of daily body weight demonstrated an
      initial trend toward improvement in the G-CSF group. Quantitative Nissl histology
      of the hippocampus demonstrated equivalent outcomes on Days 3 and 14, which was
      supported by quantitative TUNEL stain. Immunohistochemistry and Western blot
      demonstrated an initial increase in phosphorylated-AKT in the GI+G-CSF group on
      Day 2. We conclude that G-CSF treatment is associated with transient early
      improvement in neurobehavioral outcomes after global ischemia complicated by mild
      hyperglycemia, but no long-term protection.

PMID- 17210150
TI  - Oral treatment with probucol in a pharmacological dose has no beneficial effects
      on mortality in chronic ischemic heart failure after large myocardial infarction
      in rats.
AB  - Cardiac remodeling after myocardial infarction is in part triggered and
      maintained by reactive oxygen species. Antioxidants such as probucol have shown
      positive short-term effects on these cardiac interstitial changes in different
      experimental models after intraperitoneal administration or after per-oral
      administration with a long pre-treatment period or in high doses. In this study,
      the long-term effects on mortality and cardiac remodeling were examined after
      induction of a large myocardial infarction in a clinical daily-life-like setting.
      Male Lewis rats were randomized to the study groups. Large anterolateral
      myocardial infarctions were induced or sham operations performed. The oral
      treatment was started after 48 h either with probucol or placebo after myocardial
      infarction and with placebo after sham operation. Induction of large myocardial
      infarctions led to changes of the left ventricular stiffness constants, a
      dilatation of the left ventricle and an increased interstitial fibrosis in the
      remote non-infarcted part. These changes were in tendency, but not significantly,
      reversed after treatment with probucol. The 6-month survival rates were 53.1% in
      the group probucol-myocardial infarction, 43.2% in the group placebo-myocardial
      infarction and 100% in the group after sham operation. There were no significant
      differences at Kaplan-Meier analysis between the groups after myocardial
      infarctions. Oral treatment with the antioxidant probucol started after
      myocardial infarction in a pharmacological dose does not have favourable effects
      on the long-term mortality in the chronic ischemic heart failure model in the
      rat.

PMID- 17210152
TI  - Prospective study of cross-infection from upper-GI endoscopy in a hepatitis C
      prevalent population.
AB  - BACKGROUND: A high prevalence of hepatitis C (HCV) in the Egyptian Nile Delta
      increases the demand for upper-GI endoscopy (UGIE) and the risk of cross
      infection with this virus. OBJECTIVE: To assess the potential for UGIE to
      transmit HCV when endoscopes are reprocessed according to current international
      standards. DESIGN: A prospective cohort study to detect the incidence of HCV and
      hepatitis B cross-infections. SETTING: The endoscopic unit of the National Liver
      Institute, a hospital for patients with chronic liver disease. PATIENTS: A total
      of 859, including 149 of 249 patients (60%) at risk (HCV-antibody negative)
      retested 3 to 10 months after UGIE with endoscopes previously used on HCV
      carriers. INTERVENTIONS: Nurses were trained to process endoscopes according to
      American Society for Gastrointestinal Endoscopy guidelines, and procedures were
      observed and recorded. MAIN OUTCOME MEASUREMENTS: Seroconversions were determined
      by using enzyme immunoassays for anti-HCV; reverse transcriptase-polymerase chain
      reaction was used to detect HCV-ribonucleic acid (RNA). RESULTS: Four patients,
      initially negative, tested positive for anti-HCV after UGIE. However, 2 of these
      had HCV-RNA in their baseline blood sample, and the other 2 did not have HCV-RNA
      in their follow-up sample. LIMITATIONS: Very-high prevalence of anti-HCV in
      subjects reduced the proportion at risk of infection, and follow-up was
      difficult. CONCLUSIONS: There were no cases of proven transmission of HCV when
      endoscopes were reprocessed by using currently accepted standards. This negative
      study is encouraging, because patients undergoing UGIE in the Nile Delta of Egypt
      where HCV-caused liver disease is so pervasive would be at maximum risk of HCV
      cross-infection from UGIE.

PMID- 17210151
TI  - Safety and efficacy of cytology brushings versus standard FNA in evaluating
      cystic lesions of the pancreas: a pilot study.
AB  - BACKGROUND: Cystic neoplastic lesions of the pancreas (CNLP) are increasingly
      detected and are associated with a potential for malignant transformation.
      Diagnostic assessment of these lesions is often limited by the cystic nature and
      focality of neoplastic progression of these lesions. EUS-guided FNA (EUS-FNA) of
      cyst fluid and exfoliated cells is one of the most accurate methods of diagnosis
      but still has limited sensitivity. A new, through-the-needle cytologic brush
      system has recently been approved for use during EUS evaluation of cystic lesions
      of the pancreas. OBJECTIVE: To evaluate the cytologic yield and safety profile of
      the new cytobrush compared with conventional FNA in evaluating CNLP. DESIGN: Ten
      consecutive patients with CNLP were included. All cysts were sampled by standard
      EUS-FNA (0.5 of cyst volume) followed by brush cytology, then by aspiration of
      the remaining fluid. Fluid samples were separately submitted (standard FNA and
      cytobrushings FNA) but were read by the same pathologist. Complications were
      assessed during the immediate postprocedure period (2-3 hours) and by a telephone
      call conducted approximately 30 days after the procedure to inquire about any new
      symptoms, including abdominal pain, melena, hematochezia, hematemesis, fever,
      nausea, and vomiting. SETTING: High-volume EUS referral center. PATIENTS: Ten
      consecutive patients with CNLP that measured at least 20 mm in maximal dimension
      were included. MAIN OUTCOME MEASUREMENTS: Cellularity and presence of diagnostic
      cells on the FNA. RESULTS: In 7 of 10 cases, the EchoBrush specimen was superior
      to FNA in terms of cellularity and detection of diagnostic cells. Two cases had
      complications: 1 major and 1 minor intracystic bleed. No infection or
      pancreatitis was observed. LIMITATIONS: The interpreting pathologist for the case
      was not blinded to the results of either of the samples. In addition, this pilot
      study represents only a single-center experience. CONCLUSIONS: This study
      suggests that brush cytology specimens obtained at the time of EUS are superior
      to conventional FNA because of the higher yield of epithelial cells. It is
      unclear whether bleeding is more common after EchoBrush sampling; however,
      caution should be taken in patients who require anticoagulation until further
      data are available.

PMID- 17210153
TI  - Non-mucin-producing biliary papillomatosis diagnosed by transpapillary endoscopic
      curettage (with video).

PMID- 17210154
TI  - Atherosclerosis risk factors in children of parents with the metabolic syndrome.
AB  - BACKGROUND: Metabolic syndrome is a constellation of disorders that produces a
      high risk of atherosclerosis. Endothelial dysfunction is the key event in
      atherosclerosis and already present even in the childhood. The aim of the present
      study is to investigate inflammatory and radiological signs of atherosclerosis in
      children who have parents with the metabolic syndrome. DESIGN AND METHODS: Fifty
      children of parents with the metabolic syndrome and 38 age- and sex-matched
      controls were studied. Anthropometric measurements, blood pressure assessment,
      echocardiography, flow-mediated vasodilatation (FMD) which is a non-invasive test
      for the evaluation of endothelial function and fasting blood measurements
      including blood glucose, insulin, total cholesterol, HDL cholesterol,
      triglyceride, hsCRP and soluble CD40 ligand were performed. RESULTS: Serum sCD40L
      and hsCRP levels were significantly higher in the study group compared to the
      controls. FMD values did not differ between the study and control groups.
      Increased serum sCD40L levels were positively correlated with body mass index,
      waist hip ratio, LDL/HDL cholesterol ratio, and the number of metabolic syndrome
      components in parents, whereas showed negative correlation with the serum HDL
      cholesterol levels. High hsCRP levels were positively correlated with body mass
      index and the number of metabolic syndrome components. Multiple regression
      analysis demonstrated that the number of metabolic syndrome components in parents
      presented as being a significant predictor of the serum sCD40L and hsCRP levels
      of their children. CONCLUSION: Our results suggest that children of patients with
      metabolic syndrome have higher values of the serum markers of inflammation, which
      may be associated with increased risk for development of cardiovascular disease.

PMID- 17210155
TI  - Determination of Brett character responsible compounds in wines by using multiple
      headspace solid-phase microextraction.
AB  - This study presents a method based on the use of multiple headspace solid-phase
      microextraction (MHS-SPME) for the quantitative analysis of 4-ethylphenol, 4
      ethylguaiacol, 4-vinylphenol and 4-vinylguaiacol. MHS-SPME is a modification of
      SPME that implies several consecutive extractions from the same sample and avoids
      possible matrix effects. This study demonstrates the existence of a matrix effect
      in the analysis of compounds responsible for Brett character in wine when an HS
      SPME based method is used with a carbowax/divinylbenzene (CW/DVB) fibre. For this
      reason, MHS-SPME is proposed as an alternative technique with respect to HS-SPME.
      The method proposed was validated and the detection limits obtained were 0.06
      microg/l for 4-ethylguaiacol and 4-ethylphenol and, 0.20 microg/l for 4
      vinylguaiacol and 0.12 microg/l for 4-vinylphenol. These detection limits are
      below the odour detection thresholds of the compounds in wine matrices. The
      repeatability obtained, in terms of relative standard deviation (RSD), was
      considered acceptable, ranging from 1 to 12%. To evaluate the applicability of
      the proposed MHS-SPME method, concentration results were compared with those
      obtained with the standard addition method, and the results were similar with
      both methods. Furthermore, the new method was satisfactorily applied to a number
      of commercial red, white and rose wines. Therefore, MHS-SPME can be considered as
      an alternative to avoid the matrix effect in wine samples.

PMID- 17210156
TI  - Determination of five 4-hydroxycoumarin rodenticides in animal liver tissues by
      ion chromatography with fluorescence detection.
AB  - A novel analytical method is proposed for rapid simultaneous determination of
      five 4-hydroxycoumarin rodenticides in animal liver tissues by eluent generator
      reagent free ion chromatography (RFIC) with fluorescence detection. Rodenticides
      were initially extracted from homogenized animal liver tissues with ethyl acetate
      and the extracts subjected to a solid-phase extraction process using Oasis HLB
      cartridges. The IC separation was carried out on an IonPac AS11 analytical column
      (250 mm x 4.0 mm) using gradient KOH containing 10% acetonitrile as organic
      modifier at a constant flow rate of 1.0 mL/min. The analytes were detected by
      fluorescence at an excitation wavelength of 270 nm and an emission wavelength of
      380 nm. The average recoveries of the objective compounds spiked in animal liver
      tissues were between 81% and 98%. The limits of quantification (LOQs) were 0.004
      0.010 mg/kg for them. Within-day and day-to-day relative standard deviations
      (RSD) were less than 8.5% and 9.7%, respectively. It was confirmed that this
      method could be used in a toxicological analysis.

PMID- 17210157
TI  - An automated mobile phase preparation workstation.
AB  - An automated solvent dispensing workstation capable of delivering volumes ranging
      from 10 mL to 4.5 L for the preparation of solutions/mobile phases was developed
      and implemented into the industrial R&D laboratory. The workstation was designed
      to address business, safety, and compliance needs while meeting or exceeding the
      precision and accuracy of current manual methods of preparation. The system's
      performance was optimized with respect to liquid transfer tubing inner diameter,
      pumping pressure, flow characteristics of the valve, and computer control logic.
      The automated solvent dispensing workstation was shown to exceed the
      specifications set by the ASTM for Class A graduated cylinders for all dispense
      volumes (10 mL-4.5 L).

PMID- 17210158
TI  - Optimization of a procedure for the selective isolation of some powerful aroma
      thiols. Development and validation of a quantitative method for their
      determination in wine.
AB  - This paper deals with the isolation properties of four relevant wine mercaptans
      in two different separation systems and with the subsequent development,
      optimization and validation of an analytical procedure for their quantitative
      determination. 4-Methyl-4-mercaptopentanone (4M4MP), 2-furanmethanethiol (FFT), 3
      mercaptohexanol (3MH) and 3-mercaptohexyl acetate (AMH) can be quantitatively
      extracted from 200 ml of wine in a bed packed with 1 g of LiChrolut EN resins.
      Fatty acids and diverse interfering compounds are removed by rinsing with an
      aqueous solution with a 40% of methanol and buffered at pH 7.2 with
      alpha,alpha,alpha-tris-(hydroxymethyl)-aminomethane (TRIS) 0.2 M. Mercaptans can
      be further isolated by extraction with an aqueous solution of 1 mM p
      hydroxymercury benzoate. Best results were achieved with an extraction with a
      solution at pH 10.7 with 0.2 M 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid
      (HEPES), further acidification to pH 7.5, release of thiols by the addition of
      dithioerythritol and extraction with 2 x 0.75 ml dichloromethane. The extract is
      concentrated to 200 and 20 microl are finally injected in a gas chromatograph-ion
      trap mass spectrometric system. Method detection limits are 0.8, 6, 15 and 5 ng
      l(-1) for 4M4MP, FFT, MH and AMH, respectively. The recovery in the sample pre
      treatment was 76, 45, 75 and 95%, respectively. Repeatability and linearity are
      also satisfactory. Different critical aspects, such as the effect of air or the
      evaporation of the extract were also studied.

PMID- 17210159
TI  - Application of liquid chromatography-electrospray ionisation mass spectrometry
      for determination of dietary folates: effects of buffer nature and mobile phase
      composition on sensitivity and selectivity.
AB  - A sensitive and reliable liquid chromatography-mass spectrometry (LC-MS) method
      to determine dietary folates was developed and validated. Folates were detected
      and quantified using positive electrospray ionisation (ESI) with selective ion
      monitoring of protonated ions [M+H]+. The effects of buffer nature and mobile
      phase composition on separation, peak shape and intensity of MS signal were
      investigated. The acidic-basic properties of folates were successfully used to
      predict possible ionisation patterns, but they were not sufficient to predict the
      intensity of MS signal and the proportion of different ionisation products, which
      indicated that other parameters, such as gas phase acidity/basicity of analytes
      and ion evaporation mechanisms might be important. The use of aqueous acetic acid
      as volatile buffer was found to be preferable compared to formic acid due to
      considerable gain in intensity of MS signal for all folate forms studied. Limits
      of quantifications were 0.3 ng/mL for 5-methyltetrahydrofolate and 0.6 ng/mL for
      tetrahydrofolate, 10-formylfolic acid, 5-formyltetrahydrofolate and folic acid
      when using 20 microL injection. For 10-formylfolic acid, 5-formyltetrahydrofolate
      and folic acid the MS detection was found to be superior over commonly used
      fluorescence and UV detection in terms of selectivity and sensitivity. The method
      was successfully applied to analysis of folates in baker's yeast.

PMID- 17210160
TI  - Analysis of anatoxin-a in biological samples using liquid chromatography with
      fluorescence detection after solid phase extraction and solid phase
      microextraction.
AB  - Anatoxin-a is a naturally occurring, potent neurotoxin produced by some species
      of cyanobacteria in freshwaters. This toxin, which is a potential health hazard,
      especially to animals, has been determined in different biological matrices such
      as several cyanobacterial cultures and water samples and carps and mussels tissue
      using a sensitive High Performance Liquid Chromatography with Fluorescence
      detection method. Sonication was the technique selected for the extraction of
      intracellular anatoxin-a and solid phase extraction using weak cation exchange
      was used for the concentration and purification of the samples. 4-Fluoro-7-nitro
      2,1,3-benzoxadiazole (NBD-F) was used to convert anatoxin into a highly
      fluorescent derivative. Recovery experiments were performed for each type of
      matrix used in this work, and adequate values were obtained (71-87%). Limits of
      detection for anatoxin-a were estimated to be in the ng/L and ng/g level for
      water and cyanobacterial samples, respectively. The results obtained were also
      compared with those obtained after using solid phase microextraction, as an
      alternative for the extraction and purification of the samples. Advantages and
      disadvantages regarding to the efficiency for impurities removal, simplicity and
      rapidity and the potential for concentration enhancement of using both
      methodologies have been also discussed.

PMID- 17210161
TI  - Species and epitope specificity of two 65 kDa glutamate decarboxylase time
      resolved fluorometric immunoassays.
AB  - The 65 kDa isoform of human glutamate decarboxylase (GAD65) is a major
      autoantigen in type 1 diabetes (T1D). In the present study, we have developed a
      sensitive sandwich time-resolved fluorescence immunoassay (TRFIA) for the
      quantification of GAD65 in cell extracts, cell media and serum. The monoclonal
      antibody GAD-6 is used to selectively capture GAD65 but not the slightly larger
      isoform GAD67, and the utilization of different detecting antibodies with
      distinct GAD65 epitope specificity allows modulating the specificity of the
      assay. To this effect we have biotinylated a recombinant antigen-binding fragment
      (rFab) with epitope specificity for the N-terminal region of rat and human GAD65
      (rFab N-GAD65) and another rFab that selectively binds to the middle part of
      human GAD65 (rFab b96.11). In the assay the biotinylated rFabs are recognized by
      Europium labeled streptavidin. The obtained time-resolved fluorescence (TRF) is
      directly proportional to the concentration of GAD65 over a large measuring range
      (0.1 to >100 ng/mL). Based on total error estimation including both bias and
      imprecision, the lower limit of quantitation (LLOQ) of GAD65 in cell extracts is
      0.33 ng/mL with the N-GAD65 TRFIA, and 0.10 ng/mL with the b96.11 TRFIA, but the
      latter is suitable for human GAD65 only, whereas the N-GAD65 TRFIA has equal
      sensitivity with rat and human GAD65. Specificity was further checked with
      GAD65/67 fusion proteins, confirming that the presence of intact capture as well
      as detection epitope on the analyte is a prerequisite for recognition in both
      assays. We show that the beta cell-specific marker GAD65 can be quantified in
      pancreatic cell extracts and in serum, allowing studies on discharge during cell
      death in vitro as well as in vivo.

PMID- 17210162
TI  - Method for chronological recording of antigen appearance in human head-hair
      shafts and its use for monitoring glycation products in diabetes.
AB  - We describe immunochemical assays of non-enzymatic glycation products in human
      head-hair protein extracts and hair cross sections using Western blots and a
      novel "dot-block" methodology. In the latter, groups of approximately 15 hair
      fibers, clipped at about 1 mm proximal to the scalp-skin were aligned, wound
      around, and attached to 3 mm diameter araldite screw rods. Up to 40 such rods
      were next embedded lengthwise in additional araldite polymer creating a solid
      block and the top surface of the block was sectioned off to the half-diameters of
      the screw rods thus exposing accurately transected hair cross sections at regular
      ( approximately 0.5 cm) intervals. Early- and advanced-glycation products (EGAs
      and AGEs, respectively) were determined in the exposed cross sections in-situ
      using specific antibodies and ECL densitometry as in conventional Western blots.
      Both Western blots and this technique demonstrated 3.1 fold EGAs increases in the
      proximal 2 cm of hair of diabetics as compared to non-diabetics. Dot-blocks, in
      addition, were less variable and demonstrated exponential EGAs decreases along
      fibers distally, with calculated intercepts (at the hair roots) of 4.9 fold
      increases in diabetics as opposed to non-diabetics and half-lives of 6.0, 5.9 and
      9.0 months in hair of non-diabetics, gestational diabetics and diabetic patients,
      respectively. Correlations in amounts of BG vs. HbA1(c), BG vs. EGAs, and HbA1(c)
      vs. EGAs, using dot-block and clinical lab data were all significant (p<0.05).
      Acute onset T1D patients, defined as previously unsuspected patients diagnosed
      upon hospitalization due to diabetic complications, exhibited nearly identical
      EGAs levels in their proximal 0-9 cm hair as did T1D patients with long
      established diabetes, thus supporting the notion of long and insidious T1D
      etiology. Removal of 1-2 microm layers from dot-block surfaces enabled their re
      use for multiple assays. Applied anti-AGEs antibodies demonstrated slight
      decreases or no significant changes in CML and MGI along hair shafts of normal
      and diabetic subjects. Fluctuations in EGAs and AGEs along hair shafts,
      indicating alterations in glycemic control were also observed. We conclude that
      the dot-block method has a potential for early diagnosis and monitoring of
      diabetes, and more generally, as a long term "biological record" of various
      chronic medical conditions.

PMID- 17210163
TI  - Evidence of protease in the saliva of the butterfly Heliconius melpomene (L.)
      (Nymphalidae, Lepidoptera).
AB  - Butterflies of the genus Heliconius are well known for their peculiar habits of
      utilizing pollen as a source of amino acids. Saliva plays a major role in the
      process of extracting amino acids and proteins from the pollen grains. In this
      investigation, we obtained samples of saliva from adult Heliconius melpomene by
      placing pumpkin pollen or fine glass-beads on the proboscis, which stimulates the
      butterflies to release saliva. Proteolytic activity was determined in the saliva
      by an insoluble protein-dye that turns blue when cleaved by proteases. Its
      extinction value was measured with a spectrophotometer at 595 nm. Both the saliva
      sampled with pollen and the saliva obtained from inert glass-beads exhibit
      proteolytic activity demonstrating that the saliva contains proteases. The
      proteolytic activity of the pollen/saliva samples was higher than that of the
      glass-bead/saliva samples, which we attribute to the stimulating effects of
      pollen, such as taste, smell, and texture, and not to proteases which might have
      been liberated from the pollen. This is indicated by the fact that pollen samples
      without saliva showed only a negligible indication for proteolytic activity. In
      general, females exhibit higher proteolytic activities than males, presumably due
      to their greater amino acid investment in reproduction. We present here first
      evidence for the existence of proteases in the saliva of a butterfly species and
      suggest that these enzymes are crucial for the use of amino acids and proteins
      from pollen in Heliconius butterflies.

PMID- 17210164
TI  - Proteomics in clinical interventions: achievements and limitations in biomarker
      development.
AB  - Development of toxicological and clinical biomarkers for disease diagnosis,
      quantification of toxicant/drug responses and rapid patient care are major
      concerns in modern biology. Even after human genome sequencing, identification of
      specific molecular signatures for unambiguous correlation with toxicity and
      clinical interventions is a challenging task. Differential protein expression
      patterns and protein-protein interaction studies have started unraveling rigorous
      molecular explanation of multi-factorial and toxicant borne diseases. Proteome
      profiling is extensively used to investigate etiology of diseases, develop
      predictive biomarkers for toxicity and therapeutic interventions and potential
      strategies for treatment of complex and toxicant mediated diseases. In this
      review, achievements and limitations of proteomics in developing predictive
      biomarkers for toxicological and clinical interventions have been discussed.

PMID- 17210165
TI  - Fat and sugar flavor preference and acceptance in C57BL/6J and 129 mice:
      experience attenuates strain differences.
AB  - C57BL/6J (B6) mice display stronger preference and acceptance for various
      sweeteners than do 129 mice (129P3/J, 129X1/SvJ). The present experiment compared
      the preference of these strains for fat flavor as well as sweet taste using 24-h
      two-bottle preference tests. Fat flavor preference was evaluated using non
      nutritive (olestra) and nutritive (Intralipid) oil emulsions. In initial oil vs.
      water tests olestra preference and intake were greater in B6 mice than 129 mice.
      Similar strain differences were obtained with low (0.313%-5%) but not high (10%
      20%) Intralipid concentrations. When retested with Intralipid the B6 and 129 mice
      showed strong (>90%) preferences for the nutritive oil although B6 mice still
      consumed more oil at low concentrations. A second olestra test revealed increased
      oil preference and acceptance in B6 and 129X1/SvJ mice while 129P3/J mice still
      did not prefer olestra to water. Sweetener tests revealed stronger saccharin and
      sucrose preferences in B6 mice than in 129 mice. These strain differences in
      sweetener preference disappeared when the mice were retested with sucrose and
      saccharin. However, B6 mice continued to consume more saccharin and sucrose (at
      low concentrations) than did 129 mice. The profile of strain differences for non
      nutritive and nutritive oils was similar to those observed for non-nutritive and
      nutritive sweeteners. The differential sweetener preferences of B6 and 129 mice
      is explained by differences in their sweet taste receptors but why the strains
      also differ in their initial fat flavor preference is not clear. The
      experientially-induced increases in oil and sweetener preferences displayed by
      the mice are attributed to the post-oral actions of Intralipid and sucrose. These
      findings along with intragastric infusion data suggest that B6 and 129 mice
      differ in their oral but not their post-oral response to fat and sugar.

PMID- 17210166
TI  - New phytoecdysteroids from cultured plants of Ajuga nipponensis Makino.
AB  - An extract from aerial parts of Ajuga nipponensis Makino was examined by high
      performance liquid chromatography for minor ecdysteroids. Along with the
      compounds already reported, namely cyasterone, ajugasterone C, cyasterone 22
      acetate and 22-dehydrocyasterone, the presence of three additional bands with the
      expected ecdysteroid-like UV absorption was observed. The structures of the
      isolates were unambiguously elucidated based on extensive NMR spectral studies
      (one and two-dimensional experiments) and pointed out three new
      phytoecdysteroids. One of the new compounds, 22-dehydrocyasterone 2-glucoside is
      just the second example of a C-2 glucosyl derivative. The other two compounds
      displayed hemiacetal functions in the side chain, one unprecedented, and were
      named ajugacetalsterone A and B.

PMID- 17210167
TI  - Antivenom use, premedication and early adverse reactions in the management of
      snake bites in rural Papua New Guinea.
AB  - OBJECTIVE: To examine antivenom use, premedication, early adverse reactions and
      patient outcomes after snake bite in rural Papua New Guinea. DESIGN:
      Retrospective chart analysis of all admissions for snake bite with documented
      antivenom use at 11 rural health facilities from January 1994 to June 2004. No
      formal protocol was followed and there was no attempt at randomisation or
      blinding of prophylaxis. RESULTS: Antivenom use was documented in 136/1881 (7.2%)
      snake bite admissions and most (121/136: 88.9%) received a single vial. CSL
      Polyvalent antivenom was administered to 112/136 (82.4%). One hundred and eleven
      patients (81.6%) happened to have been given premedication with adrenaline and/or
      promethazine and/or hydrocortisone. Early adverse reactions were reported in 25
      patients (18.4%) including 23 treated with polyvalent antivenom. Intravenous test
      doses of antivenom were given to 32 patients, none of whom had a positive test
      result. Subsequent adverse reactions occurred in 9 of these 32 (28.1%) patients.
      One death may have been attributable to anaphylaxis after polyvalent antivenom.
      Reaction rates were significantly (p < or = 0.005) lower in adrenaline
      premedicated patients (7.7%) compared to patients premedicated without adrenaline
      (28.3%) and unpremedicated patients (28.0%). Adrenaline premedication caused no
      detectable changes in vital signs. The case fatality rate was 9.6% (13/136
      patients). CONCLUSIONS: Polyvalent antivenom is the main treatment for
      envenomation in rural health centres, and early adverse reactions are common.
      Adrenaline premedication appears to significantly reduce acute adverse reaction
      rates. Premedication with promethazine and/or hydrocortisone without adrenaline
      did not reduce early adverse reactions.

PMID- 17210169
TI  - Hyaluronidases in Loxosceles intermedia (Brown spider) venom are endo-beta-N
      acetyl-d-hexosaminidases hydrolases.
AB  - In studying Loxosceles venom, we detected degradation of purified hyaluronic acid
      (HA) and hydrolysis of purified chondroitin sulphate (CS) while neither dermatan
      sulphate, heparin or heparan sulphate were affected. In addition, with HA
      degrading kinetic assays, we show that a hydrolase enzyme was involved in the HA
      cleavage. By use of the Reissig colorimetric reaction, we found that venom
      hyaluronidase is an endo-beta-N-acetyl-d-hexosaminidase that generates terminal N
      acetylglucosamine residues upon cleavage of HA. Zymogram analysis of L.
      intermedia venom showed HA lytic activities at 41 and 43kDa, and, when CS was
      used as a substrate, zymograph experiments resulted in 41 and 43kDa lytic zones.
      Thus, these results support the hypothesis that the same molecules are involved
      in cleaving HA and CS residues. Experiments to compare L. intermedia
      electrostimulated venom and venom gland extract also demonstrated very similar HA
      lytic activity, suggesting again that hyaluronidases are self-components of
      Loxosceles spider venom instead of oral egesta contamination. HA degradation as a
      function of pH in these hydrolase enzymes showed no apparent activities at low or
      high pH, with optimal activity at 6.0-8.0 pH. Finally, we confirmed the cleaving
      action of the venom hyaluronidases on HA in the extracellular matrix of the
      dermis of rabbit by fluorescence reaction to HA and confocal microscope analysis.
      Thus, hyaluronidases type hydrolases endo-beta-N-acetyl-d-hexosaminidase are
      implicated as self-components of Loxosceles spider venom and can be involved in
      venom effects as spreading factors.

PMID- 17210168
TI  - Insecticidal toxins from black widow spider venom.
AB  - The biological effects of Latrodectus spider venom are similar in animals from
      different phyla, but these symptoms are caused by distinct phylum-specific
      neurotoxins (collectively called latrotoxins) with molecular masses ranging from
      110 to 140 kDa. To date, the venom has been found to contain five insecticidal
      toxins, termed alpha, beta, gamma, delta and epsilon-latroinsectotoxins (LITs).
      There is also a vertebrate-specific neurotoxin, alpha-latrotoxin (alpha-LTX), and
      one toxin affecting crustaceans, alpha-latrocrustatoxin (alpha-LCT). These toxins
      stimulate massive release of neurotransmitters from nerve terminals and act (1)
      by binding to specific receptors, some of which mediate an exocytotic signal, and
      (2) by inserting themselves into the membrane and forming ion-permeable pores.
      Specific receptors for LITs have yet to be identified, but all three classes of
      vertebrate receptors known to bind alpha-LTX are also present in insects. All
      LTXs whose structures have been elucidated (alpha-LIT, delta-LIT, alpha-LTX and
      alpha-LCT) are highly homologous and have a similar domain architecture, which
      consists of a unique N-terminal sequence and a large domain composed of 13-22
      ankyrin repeats. Three-dimensional (3D) structure analysis, so far done for alpha
      LTX only, has revealed its dimeric nature and an ability to form symmetrical
      tetramers, a feature probably common to all LTXs. Only tetramers have been
      observed to insert into membranes and form pores. A preliminary 3D reconstruction
      of a delta-LIT monomer demonstrates the spatial similarity of this toxin to the
      monomer of alpha-LTX.

PMID- 17210170
TI  - The intracellular sites of early replication and budding of SARS-coronavirus.
AB  - In this study, we analyzed the replication and budding sites of severe acute
      respiratory syndrome coronavirus (SARS-CoV) at early time points of infection. We
      detected cytoplasmic accumulations containing the viral nucleocapsid protein,
      viral RNA and the non-structural protein nsp3. Using EM techniques, we found that
      these putative viral replication sites were associated with characteristic
      membrane tubules and double membrane vesicles that most probably originated from
      ER cisternae. In addition to its presence at the replication sites, N also
      accumulated in the Golgi region and colocalized with the viral spike protein.
      Immuno-EM revealed that budding occurred at membranes of the ERGIC (ER-Golgi
      intermediate compartment) and the Golgi region as early as 3 h post infection,
      demonstrating that SARS-CoV replicates surprisingly fast. Our data suggest that
      SARS-CoV establishes replication complexes at ER-derived membranes. Later on,
      viral nucleocapsids have to be transported to the budding sites in the Golgi
      region where the viral glycoproteins accumulate and particle formation occurs.

PMID- 17210171
TI  - Biomarker versus environmental factors: seasonal variations and modelling
      multixenobiotic defence (MXD) transport activity in transplanted zebra mussels.
AB  - The occurrence of biomarker temporal variations linked to environmental factors
      makes it difficult to distinguish the specific effect of pollution. The present
      work aims to investigate the seasonal variations of the transport activity of the
      multixenobiotic defence (MXD), which is used as a biological tool for the
      monitoring of pollution in aquatic ecosystems. The MXD transport activity was
      monitored monthly from August 2001 to October 2002 in zebra mussels (Dreissena
      polymorpha) transplanted to three sites in the Moselle River. The 'efflux method'
      was used to evaluate functional activity of MXD by assessing rhodamine B efflux
      with or without an inhibitor (verapamil). Environmental parameters were provided
      by a French regulatory agency (Water Agency) that monitors river water quality.
      The results of a principal components analysis describe the seasonal cycle of
      water characteristics and demonstrate that MXD activity is subjected to
      significant temporal variations. These data were described with a generalised
      linear model that enables it to link MXD variability to the seasonal variations
      of environmental parameters such as temperature or levels of organic
      contamination. This work proposes a modelling approach and highlights that the
      occurrence of seasonal variations in MXD response has to be taken into account in
      the interpretation of in situ monitoring studies.

PMID- 17210172
TI  - Effects of human versus mouse leukemia inhibitory factor on the in vitro
      development of bovine embryos.
AB  - Leukemia inhibitory factor (LIF) is a cytokine that shows conflicting effects on
      in vitro produced (IVP) bovine embryos. Bovine LIF (bLIF) has been cloned and
      used in culture, but there is no commercially available bLIF. Thus, researchers
      use human LIF (hLIF) to supplement the culture medium for bovine embryos because
      of its greater sequence homology compared to murine LIF (mLIF). We compared the
      effects of mLIF and hLIF on the development of bovine embryos in culture with the
      effects described for bLIF. Oocytes were matured and fertilized in vitro and
      cultured in modified synthetic oviduct fluid with BSA. On Day 6 post
      insemination, morulae were cultured for 48h in the presence of: (1) mLIF,
      100ngml(-1); (2) hLIF, 100ngml(-1); or (3) no LIF. Reduced blastocyst rates were
      observed on Day 8 for hLIF at the middle and expanded stages, while mLIF had no
      effect. In contrast, Day 8 blastocysts showed decreased cell counts both in terms
      of inner cell mass (ICM) and ICM/total cell proportions in the presence of mLIF,
      while hLIF had no effect. No changes were seen in trophectoderm (TE) and total
      cell counts. The increased hatching rates and TE cell counts previously described
      for bLIF, together with the disparate effects exhibited by hLIF and mLIF during
      blastocyst formation indicate these compounds are inappropriate to replace bLIF.
      We recommend that heterospecific LIF should not be used to supplement the culture
      medium for bovine embryo or embryonic stem cells.

PMID- 17210173
TI  - Wear of composite resin veneering materials and enamel in a chewing simulator.
AB  - OBJECTIVES: The purpose of this in vitro study was to evaluate the wear of six
      composite resins for the veneering of crowns compared with the wear of human and
      bovine enamel, tested in a dual-axis chewing simulator. METHODS: Eight specimens
      of six different composite resins (Targis I+II, Solidex, BelleglassHP, Estenia,
      Solidex) and of human and bovine enamel were prepared. Steatite ceramic balls
      served as antagonistic specimens. Specimens were dynamically loaded in a dual
      axis chewing simulator with 49 N up to 1,200,000 loading cycles with additional
      thermal cycling between 5 and 55 degrees C. After 120,000, 240,000, 480,000,
      840,000 and 1,200,000 loading cycles, an impression of the specimens' surface and
      the antagonistic specimen was taken using a polyvinylsiloxane impression
      material. The substance loss at the surface was measured with computer-aided
      laser profilometry. Data were analyzed using ANOVA and the Tukey test. RESULTS:
      The wear of the ultra fine compact filled composite resins Solidex and
      BelleglassHP was not statistically significantly different from that of human
      enamel. The other composite resins and bovine enamel showed a wear statistically
      significantly higher than human enamel. SIGNIFICANCE: Comparing six composite
      resins for the veneering of crowns, ultra fine compact filled composite resins
      BelleGlassHP and Solidex showed a wear not significantly different from the wear
      of human and bovine enamel.

PMID- 17210174
TI  - The effect of pressure on the glass transition of biopolymer/co-solute. Part I:
      The example of gelatin.
AB  - High-solid materials of gelatin in the presence of co-solute were prepared and
      subjected to a series of hydrostatic pressures up to 700 MPa. Following this, a
      study was made of the relaxation properties of the mixture around the glass
      transition region and the melting behaviour of the gelatin network. Structural
      properties were monitored using differential scanning calorimetry and small
      deformation dynamic oscillation on shear. Thermograms were obtained and master
      curves of viscoelasticity were constructed for each experimental pressure. The
      dependence of the empirical shift distances obtained from mechanical measurements
      and supplementing evidence from thermal analysis argue that the application of
      pressure did not alter the vitrification or melting characteristics of the
      gelatin/co-solute system within the experimentally accessible pressure range.
      Unlike the principle of the time-temperature-pressure superposition applicable to
      synthetic macromolecules, it may not be possible to incorporate a pressure
      component into the framework of thermorheological simplicity governing the glass
      transition of the high-sugar gelatin network.

PMID- 17210175
TI  - Primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (post-PV MF),
      post essential thrombocythemia myelofibrosis (post-ET MF), blast phase PMF (PMF
      BP): Consensus on terminology by the international working group for
      myelofibrosis research and treatment (IWG-MRT).
AB  - The International Working Group for Myelofibrosis Research and Treatment (IWG
      MRT) is comprised of hematologists, hematopathologists, and laboratory scientists
      and its main goal is to provide a forum for scientific exchange and
      collaboration. During its first general meeting in April 2006, the IWG-MRT
      established uniform treatment response criteria for chronic idiopathic
      myelofibrosis (CIMF); also known as agnogenic myeloid metaplasia (AMM),
      myelofibrosis with myeloid metaplasia (MMM), and many other names in the
      hematologic literature. This document summarizes the proceedings from the second
      meeting of the IWG-MRT, in November 2006, where the group discussed and agreed to
      standardize the nomenclature referring to CIMF: (i) the term primary
      myelofibrosis (PMF) was chosen over several other designations including CIMF,
      AMM, and MMM, (ii) myelofibrosis that develops in the setting of either
      polycythemia vera (PV) or essential thrombocythemia (ET) will be referred to as
      post-PV MF and post-ET MF, respectively, and (iii) "leukemic" transformation will
      be recognized as blast phase disease (PMF-BP, post-PV/ET MF in blast phase).

PMID- 17210176
TI  - A therapy resistant myelodysplastic syndrome characterized by the presence of the
      rare reciprocal translocation t(3;12)(q26.2;p13).

PMID- 17210177
TI  - Collaboration, integration and change in children's services: critical issues and
      key ingredients.
AB  - BACKGROUND: Government and state policy, irrespective of jurisdiction,
      increasingly require and indeed specify the nature of collaboration with regard
      to the delivery of child welfare services for maltreated children. The rationale
      for collaboration appears obvious in as much as it is aimed at promoting
      multidisciplinary practice in order to meet the needs of the vulnerable child.
      However, collaboration, whilst a useful and motivating concept, is in reality far
      from straightforward and contains complexities and ambiguities. AIM: The aim of
      this paper is to explore these complexities and ambiguities to provide an
      overview of key developmental frameworks relevant to the creation and maintenance
      of strategic high-level multiagency partnerships. COMMENTARY: The authors begin
      by exploring the characteristic features of different levels of multiagency
      collaboration that is communication, co-operation, co-ordination, coalition, and
      integration. As the emphasis in a variety of jurisdictions in the Western world
      is on the highest levels of collaboration namely coalition and service
      integration this is the focus of the paper. The authors synthesize the main
      literature in the field to consider the critical elements for effective
      collaborative endeavors at this level including predisposing factors, mandate,
      leadership, machinery, process, and outcomes. The paper concludes by recognizing
      that the drive towards integrated services is occurring in a climate of
      continuing change. The need to identify the impact of such an environment when
      managing multiagency partnerships is explored using five steps to change.

PMID- 17210178
TI  - Hedistin: A novel antimicrobial peptide containing bromotryptophan constitutively
      expressed in the NK cells-like of the marine annelid, Nereis diversicolor.
AB  - A novel antimicrobial peptide, named hedistin was identified from the
      coelomocytes of Nereis diversicolor. Hedistin shows no obvious similarities with
      other known peptides and constitutes the first antimicrobial peptide containing
      bromotryptophans demonstrated in annelids. cDNA and mass spectrometry analysis
      revealed that, upon bacteria challenge, this peptide is secreted following
      processing of a precursor containing a signal peptide and prosequences. Hedistin
      was shown to possess an activity against a large spectrum of bacteria including
      the methicillin resistant Staphylococcus aureus and Vibrio alginolyticus. The
      gene was demonstrated to be constitutively and exclusively expressed in
      circulating NK cells like known to play an important role in the immunity of the
      sand worm. These data contrast with those observed in another annelid, the leech,
      in which genes coding for antimicrobial peptides are upregulated in a specific
      tissue and peptides are rapidly released into the hemolymph after septic injury.

PMID- 17210179
TI  - Appetitive conditioning: neural bases and implications for psychopathology.
AB  - Appetitive conditioning is the process through which new rewards are learned and
      acquire their motivational salience. Although it has the same evolutionary
      survival significance as aversive conditioning, appetitive conditioning has
      rarely been studied in humans. This gap may be explained by the difficulty to
      find in humans suitable appetitive stimuli that can elicit physiological
      responses similar to those elicited by aversive stimuli. To help remedy this gap,
      we review the literature on conditioning, with emphasis on appetitive
      conditioning. This review comprises three parts. First, we examine the different
      forms of conditioning. Second, we review the neural basis of appetitive
      conditioning, particularly from a functional neuroimaging perspective. And third,
      we demonstrate how perturbations in processes involved in appetitive conditioning
      can contribute to implicated psychopathologies and suggest neurobiological models
      underlying these pathologies. The ultimate goal of this review is to stimulate
      new avenues of research that have direct links to molecular biology, and thus
      could prove to be invaluable to progress in the understanding and treatment of
      psychiatric disabilities.

PMID- 17210180
TI  - Selection of human antibodies against cell surface-associated oligomeric anthrax
      protective antigen.
AB  - The protective antigen (PA(83)) of Bacillus anthracis is the dominant antigen in
      natural and vaccine-induced immunity to anthrax infection. Three human single
      chain variable fragments (scFvs) against cell bound PA were isolated from an
      antibody phage display library. Specifically, the antibodies were evaluated for
      their ability to bind to cell bound heptameric PA and ultimately protect against
      the cytotoxicity of lethal toxin. In total, all three scFvs possessed
      neutralizing activity against the cytotoxic effects of lethal toxin in a
      macrophage lysis assay. The K(d) values of the Fabs were determined,
      interestingly their protective effects did not parallel their affinities; hence,
      a simple binding argument alone to PA(63) cannot be used as the distinguishing
      feature for the prediction of their neutralization abilities. Immunofluorescent
      microscopy experiments were conducted and provided strong evidence for Fab
      binding to oligomeric PA on the cell surface and thus a plausible mechanism for
      the toxin neutralization activity that was observed. The results of this study
      presented herein suggest that our antibodies compete with LF-PA cell surface
      interactions, and thus may provide potential application of human antibodies as
      passive immunization prophylactics in cases of B. anthracis exposure and
      infection.

PMID- 17210182
TI  - Longitudinal study of the ocular complications of AIDS: 2. Ocular examination
      results at enrollment.
AB  - OBJECTIVE: To report the clinical features on eye examination of patients with
      AIDS in the era of highly active antiretroviral therapy (HAART). DESIGN: Cohort
      study. PARTICIPANTS: Patients with AIDS, age > or = 13 years. METHODS:
      Ophthalmologic examination, contrast sensitivity, visual fields, and laboratory
      testing at enrollment. MAIN OUTCOME MEASURES: Eye examination findings at
      enrollment. RESULTS: As of March 31, 2003, 1632 participants with AIDS were
      enrolled. Evidence of intraocular inflammation was substantially more common
      among patients with cytomegalovirus (CMV) retinitis or other major ocular
      complications than among those without, as were the complications of infection
      and inflammation, including cataracts, pseudophakia, macular edema, and
      epiretinal membrane. Among patients with CMV retinitis, macular edema and
      epiretinal membrane formation were most common among patients with long-standing
      retinitis and immune recovery. Patients with newly diagnosed retinitis had eye
      examination findings similar to those reported in the pre-HAART era. Visual
      impairment (<20/40) in the better-seeing eye was present in 9.2% of patients with
      CMV retinitis, 41.4% of patients with other major ocular complications (primarily
      ocular opportunistic infections), and only 0.6% of patients with no major ocular
      complication (P<.0001). Although patients without major ocular complications
      generally had good visual acuity, approximately 9.8% of eyes and 6.6% of
      participants had contrast sensitivity loss sufficient to impair reading speed.
      CONCLUSIONS: In the HAART era, CMV retinitis and other ocular opportunistic
      infections are associated with intraocular inflammation, structural ocular
      complications, and visual impairment. Patients with newly diagnosed CMV retinitis
      have eye examination findings similar to those seen in the pre-HAART era.

PMID- 17210181
TI  - Determinants of normal retinal nerve fiber layer thickness measured by Stratus
      OCT.
AB  - PURPOSE: To determine the effects of age, optic disc area, ethnicity, eye,
      gender, and axial length on the retinal nerve fiber layer (RNFL) in the normal
      human eye as measured by Stratus OCT (optical coherence tomography). DESIGN:
      Cross-sectional observational study. PARTICIPANTS: Three hundred twenty-eight
      normal subjects 18 to 85 years old. METHODS: Peripapillary Fast RNFL scans
      performed by Stratus OCT with a nominal diameter of 3.46 mm centered on the optic
      disc were performed on one randomly selected eye of each subject. MAIN OUTCOME
      MEASURES: Linear regression analysis of the effects of age, ethnicity, gender,
      eye, axial length, and optic disc area on peripapillary RNFL thickness. RESULTS:
      The mean RNFL thickness for the entire population was 100.1 microm (standard
      deviation, 11.6). Thinner RNFL measurements were associated with older age
      (P<0.001); being Caucasian, versus being either Hispanic or Asian (P = 0.006);
      greater axial length (P<0.001); or smaller optic disc area (P = 0.010). For every
      decade of increased age, mean RNFL thickness measured thinner by approximately
      2.0 microm (95% confidence interval [CI], 1.2-2.8). For every 1-mm-greater axial
      length, mean RNFL thickness measured thinner by approximately 2.2 microm (95% CI,
      1.1-3.4). For every increase in square millimeter of optic disc area, mean RNFL
      thickness increased by approximately 3.3 microm (95% CI, 0.6-5.6). Comparisons
      between ethnic groups revealed that Caucasians had mean RNFL values (98.1+/-10.9
      microm) slightly thinner than those of Hispanics (103.7+/-11.6 microm; P = 0.022)
      or Asians (105.8+/-9.2 microm; P = 0.043). There was no relationship between RNFL
      thickness and eye or gender. CONCLUSIONS: Retinal nerve fiber layer thickness, as
      measured by Stratus OCT, varies significantly with age, ethnicity, axial length,
      and optic disc area. These variables may need to be taken into account when
      evaluating patients for diagnosis and follow-up of glaucoma, particularly at the
      lower boundary of the normal range. Due to the relatively small numbers of
      subjects of Asian and African descent in the normative database, conclusions
      regarding the effect of ethnicity should be interpreted with caution.

PMID- 17210183
TI  - Induced binding of proteins by ammonium sulfate in affinity and ion-exchange
      column chromatography.
AB  - In general, proteins bind to affinity or ion-exchange columns at low salt
      concentrations, and the bound proteins are eluted by raising the salt
      concentration, changing the solvent pH, or adding competing ligands. Blue
      Sepharose is often used to remove bovine serum albumin (BSA) from samples, but
      when we applied BSA to Blue-Sepharose in 20 mM phosphate, pH 7.0, 50%-60% of the
      protein flowed through the column; however, complete binding of BSA was achieved
      by the addition of 2 M ammonium sulfate (AS) to the column equilibration buffer
      and the sample. The bound protein was eluted by decreasing the AS concentration
      or by adding 1 M NaCl or arginine. AS at high concentrations resulted in binding
      of BSA even to an ion-exchange column, Q-Sepharose, at pH 7.0. Thus, although
      moderate salt concentrations elute proteins from Blue-Sepharose or ion-exchange
      columns, proteins can be bound to these columns under extreme salting-out
      conditions. Similar enhanced binding of proteins by AS was observed with an ATP
      affinity column.

PMID- 17210184
TI  - Cloning and expression of the human augmenter of liver regeneration at low
      temperature in Escherichia coli.
AB  - Acute and chronic hepatic failure is a devastating illness of varied causes with
      considerable mortality. Human augmenter of liver regeneration (hALR) is a
      hepatotrophic protein and the unique cytokine which can specially stimulate
      hepatic origin cells to grow regardless of genus. It has been proven that ALR can
      promote regeneration and avoid all kinds of injury in rat and canine models. In
      this study, the recombinant protein hALR was expressed successfully with
      recombinant prokaryotic expression vector pET28a(+) in Escherichia coli BL21
      (DE3). We constructed the recombinant expression vector pET28a(+)/hALR with a
      full-length cDNA encoding hALR protein from normal human liver tissue by one-step
      reverse transcription-polymerase chain reaction and his-tag recognition sequence
      encoding polyhistidine (6 x His). Under IPTG (isopropyl-beta-d
      thiogalactopyranoside) induction for 2 h at 37 degrees C, recombinant protein
      hALR was expressed. The expression of recombinant polyhistidine-tagged hALR was
      increased under low temperature and was confirmed that the temperature of 23
      degrees C was the most suitable IPTG induction condition. Under low temperature
      induction of IPTG, recombinant protein can be expressed as a soluble protein.
      Recombinant protein hALR was also purified with His Bind Kits and characterized
      with SDS-PAGE and Western blotting. The results showed that recombinant hALR
      could be expressed as a soluble protein under low temperature induction of IPTG.
      The successful expression of ALR in E. coli makes it possible to further study
      its biological function and purified recombinant hALR could be developed into a
      new anti-hepatic damage product.

PMID- 17210185
TI  - Intraperitoneal recombinant interleukin-2 activates leukocytes in rat
      endometriosis.
AB  - The aim of this double-blinded study was to determine changes in leukocyte
      populations in blood, peritoneal lavage fluid, eutopic and ectopic endometrium
      after treatment with recombinant rat interleukin-2 (IL-2) using an in vivo
      experimental model of rat endometriosis. The in vivo model involved transplanting
      four square fragments of autologous endometrium onto the inner surface of the
      abdominal wall in 20 Wistar rats. The control group was constituted by 20 sham
      operated rats. Both groups were randomly treated (1-month interval treatment)
      with 2 intraperitoneal doses of glucose solution (5%) that did or did not contain
      recombinant IL-2, and animals were sacrificed 4 weeks after the last dose of
      treatment. Blood and peritoneal lavage were obtained during the initial and final
      laparotomy, whereas eutopic and ectopic endometrium were collected at the end of
      the experiment. Endometriotic implants were measured in each laparotomy to
      determine any change in size. Leukocyte populations were analyzed by flow
      cytometry and immunofluorescence microscopy. Cytometric results were similar in
      blood and peritoneal lavage. CD25+ and natural killer (NK) cell levels in
      peripheral blood were lower in rats with endometriosis treated with IL-2, whereas
      NK cells increased in lavage compared to placebo group. The percentage of
      macrophages and dendritic cells in blood were higher in all rats treated with IL
      2, as well as peritoneal dendritic cells. Implant size of these rats decreased
      significantly, showing a greater number of activated lymphocytes, macrophages, NK
      and dendritic cells inside them. In conclusion, recombinant IL-2 induced
      recruitment of activated leukocytes into endometriotic-like foci, and this was
      related to a reduction of the implant size, suggesting potential effectiveness of
      IL-2 as an immunomodulatory agent in this pathology.

PMID- 17210186
TI  - Cellular damage in bacterial meningitis: an interplay of bacterial and host
      driven toxicity.
AB  - Bacterial meningitis is still an important infectious disease causing death and
      disability. Invasive bacterial infections of the CNS generate some of the most
      powerful inflammatory responses known in medicine. Although the components of
      bacterial cell surfaces are now chemically defined in exquisite detail and the
      interaction with several receptor pathways has been discovered, it is only very
      recently that studies combining these advanced biochemical and cell biological
      tools have been done. Additional to the immunological response direct bacterial
      toxicity has been identified as an important contributor to neuronal damage. A
      detailed understanding of the complex interaction of bacterial toxicity and host
      response may generate opportunities for innovative and specific neuroprotective
      therapies.

PMID- 17210187
TI  - An improved method for the recovery of recombinant paramyxovirus vaccine
      candidates suitable for use in human clinical trials.
AB  - We describe a method for the generation of clinical grade, live-attenuated
      vaccines in Vero cells entirely from cDNA plasmids. The entire electroporation
      procedure can be completed in less than 15 minutes and this is a significant
      improvement over previous lipid or electroporation based transfection techniques
      that also involve a heat-shock step. Importantly, the virus preparations can be
      generated with a minimal use of animal product derived materials, an important
      consideration for a vaccine candidate that is to be tested in humans. Since it is
      likely that all live-attenuated parainfluenza virus and pneumovirus vaccines in
      the future will be generated using reverse genetics, this simplified method
      provides guidance on how this can be achieved.

PMID- 17210188
TI  - Direct evidence for immunomodulatory properties of ribavirin on T-cell reactivity
      to hepatitis C virus.
AB  - BACKGROUND/AIM: An understanding of ribavirin's beneficial effects on treatment
      outcome in chronic hepatitis C (CH-C) may help to develop new treatment
      approaches. Here we investigated whether ribavirin directly affects HCV-specific
      reactivity of CD4+T-lymphocytes from patients with CH-C. METHODS: Peripheral
      blood mononuclear cells from forty HCV RNA positive patients were cultured ex
      vivo with HCV core, NS3, NS4 alone, and with different concentrations of
      ribavirin. Virus-specific CD4+ T-cell reactivity was analysed by a proliferation
      assay; quantitation of cytokine (interferon-gamma, IL-10, IL-5, IL-12p35, IL
      12p40) mRNA levels; measurement of interferon-gamma and IL-10 production (by
      ELISA) and enumeration of interferon-gamma and IL-10 producing T-cells by Elispot
      assays. RESULTS: At 2-5 microM ribavirin induced de novo or enhanced T-cell
      proliferation to HCV antigens in a proportion of patients. Increased T-cell
      proliferation was associated with decreased IL-10 production in response to HCV
      core and reduced frequency of IL-10 producing CD4+ T-cells, while interferon
      gamma levels remained unchanged. At 20 microM ribavirin markedly suppressed T
      cell proliferation, and interferon-gamma mRNA expression to HCV antigens.
      CONCLUSIONS: Ribavirin, at clinically achievable plasma levels, modulates
      directly the T-cell responses to HCV antigens in some CH-C patients. Suppression
      of IL-10 production may represent a useful strategy to induce/augment T-cell
      reactivity to HCV.

PMID- 17210189
TI  - Prophylactic treatment with recombinant Eimeria protein, alone or in combination
      with an agonist cocktail, protects mice from Banzi virus infection.
AB  - A recombinant Eimeria protozoan protein antigen (rEA) has been shown to have
      antitumor and antiviral activity. The purpose of this study was to determine the
      effect of rEA treatment alone or in combination with an agonist cocktail
      consisting of granulocyte macrophage colony stimulating factor (GM-CSF),
      interferon gamma (IFN-gamma), interleukin 4 (IL-4), and anti CD-40 antibody, in
      the treatment of Banzi virus (BV) disease in BALB/c mice. Treatment with rEA
      resulted in a significant increase in survival, weight gain, and mean day to
      death in BV-infected mice and resulted in a significant decrease in brain virus
      titer. Treatment with rEA, in combination with a 4-agonist cocktail, improved
      disease parameters to a greater degree than rEA treatment alone. The effect of
      treatment with a reduced concentration of agonist cocktail or fewer components of
      the agonist cocktail, in combination with rEA, on disease outcome in BV-infected
      mice was also investigated. Treatment with rEA, alone or in combination with
      agonist cocktail, 24h after virus challenge did not improve disease. Treatment
      with rEA, alone or in combination with an agonist cocktail, is efficacious for
      the prophylaxis of BV infection in mice.

PMID- 17210190
TI  - Lithium improves the behavioral disorder in rats subjected to transient global
      cerebral ischemia.
AB  - Previous study has indicated that chronic treatment with lithium protects brain
      against ischemic injury by reducing apoptotic death. To investigate whether
      lithium improves the behavioral disorder induced by transient global cerebral
      ischemia, we examined the effects of lithium treatment on the performance of rats
      in a set of behavioral tests, i.e. beam balance, elevated plus maze (EPM), open
      field and Morris water maze. Our results showed that lithium attenuated the worse
      general 'well-being' and the worse performance in beam balance, and hyperactivity
      in EPM and open field, including increased open arm entries, time spent in the
      open arms, squares crossed, rearing and grooming over 7 days after 15min
      ischemia, which were induced by four-vessel occlusion in Sprague-Dawley rats.
      Moreover, lithium improved the injured spatial learning and memory ability in
      Morris water maze at post-ischemic days 8 and 9. Histological analysis displayed
      that it decreased obviously cell death in hippocampal CA1 region. Our study
      further confirmed the protective role of lithium in the ischemia-reperfusion
      injury and suggested that lithium might be a helpful therapeutic approach to the
      treatment of stroke combining with other neuroprotective agents.

PMID- 17210191
TI  - Non-steroidal anti-inflammatory drugs disrupt the heat shock response in rainbow
      trout.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDS) have been detected in the aquatic
      environment, but little is known about either their impact or mode of action in
      aquatic organisms. We tested the hypothesis that NSAIDs disrupt the
      evolutionarily conserved heat shock response, critical for defense against
      stressor-mediated proteotoxicity, in rainbow trout (Oncorhynchus mykiss). Trout
      fry were exposed by immersion to a range of salicylate or ibuprofen
      concentrations (1, 10, 100 or 1000 microg/L) for 4d. Ibuprofen, but not
      salicylate, at all concentrations induced heat shock protein 70 (hsp70) in trout
      liver. We used the highest concentration of the drugs to investigate their mode
      of action on the heat shock response. Fry were subjected to a standardized heat
      shock, 10 degrees C above ambient (13 degrees C) for 1h, and the temporal changes
      in liver hsp70 mRNA and protein content as well as glucose dynamics during
      recovery from the heat stressor assessed. Ibuprofen exposure did not modify hsp70
      mRNA abundance, but significantly depressed the heat shock-induced hsp70 protein
      expression in the liver and gill of trout. Salicylate exposure elevated hsp70
      mRNA abundance and delayed the hsp70 expression after a heat shock. Liver glucose
      levels and the activities of hexokinase, pyruvate kinase and lactate
      dehydrogenase, were elevated by NSAIDs suggesting enhanced tissue glycolytic
      capacity. Effects on whole body glucose dynamics, induced by the heat shock, were
      either absent with ibuprofen or completely modified by salicylate. Overall,
      NSAIDs disrupt the heat shock response in rainbow trout, while the mode of action
      of salicylate and ibuprofen in impacting the cellular stress response appears
      distinct.

PMID- 17210192
TI  - Molecular cloning and characterisation of Ts8B1, Ts8B2 and Ts8B3, three new
      members of the Taenia solium metacestode 8 kDa diagnostic antigen family.
AB  - Antibody screening of a lambdaZAP-XR Taenia solium metacestode cDNA library
      yielded a clone (Ts8B1), with an insert of 345 bp, and an open reading frame of
      258 bp, that coded for a protein with 85 amino acid residues. Alignment of the
      predicted amino acid sequence with sequences from SWISSPROT revealed an 88%
      identity with TcA5.5, a 10 kDa immunodiagnostic antigen of T. crassiceps, 75%
      identity with CyDA a T. solium metacestode antigen, 40-50% identity with several
      variants of the 8 kDa subunit of antigen B of Echinococcus spp. and with members
      of the T. solium metacestode 8 kDa antigen family. Two other Ts8B1 related
      molecules, Ts8B2 and Ts8B3, were identified in the metacestode cDNA library by
      PCR, coding for 85 and 66 amino acid polypeptides, respectively. Both Ts8B1 and
      Ts8B2 were characterized as E/S antigens through their subcellular localisation
      in the secretory membrane system when expressed in NRK cells. The three cDNA
      inserts were expressed, purified and probed in enzyme-linked immunosorbent assays
      (ELISA) with sera and cerebro-spinal fluid from patients with confirmed
      neurocysticercosis, and with sera from pigs infected with T. solium. The most
      promising antigen, Ts8B2, performed with a sensitivity of 96.8% and specificity
      of 93.1% in the detection of active NCC when using serum samples in the assay and
      performed similarly in the porcine system. The implications of these findings are
      discussed.

PMID- 17210193
TI  - Loser cows in Danish dairy herds: definition, prevalence and consequences.
AB  - During the last few years, many Danish dairy farmers have expressed increasing
      concerns regarding a group of cows, which we have chosen to term 'loser cows'.
      Until now, a loser cow has not been described scientifically. We defined a loser
      cow on the basis of a clinical examination of the cow. A total of 15,151 clinical
      examinations were made on 6,451 individual cows from 39 randomly selected, large
      Danish dairy herds with loose-housing systems using a clinical protocol. Scores
      for the clinical signs lameness, body condition, hock lesions, other cutaneous
      lesions, vaginal discharge, condition of hair coat and general condition were
      converted into a loser cow score. Cows with a loser cow score of 8 or more were
      classified as loser cows. The overall prevalence of loser cows was 2.15%, 4.50%
      and 2.98% during the first, second and third round of herd visits, respectively.
      The associations between the loser cow state and milk production, mortality,
      morbidity, culling and workload for the farmer were evaluated using data from
      herd visits and from the Danish Cattle Database and a number of different
      statistical techniques. It was concluded that the loser cow state has significant
      negative consequences for both the farmer and the cow. On average, loser cows
      yielded 0.61 to 2.24 kg energy corrected milk less per day than non-loser cows
      depending on parity. Hazard ratio for death or euthanasia was 5.69 for loser cows
      compared to non-loser cows. Incidence rate ratio for disease treatments was 0.69
      for non-loser cows compared to loser cows. Loser cows were often culled in an
      'unfavourable' way and generally caused extra workload for the farmer. A
      simplified version of the loser cow score was evaluated and is recommended for
      future research and use in practice.

PMID- 17210194
TI  - Epidemiological aspects of canine babesiosis in the semiarid area of the state of
      Minas Gerais, Brazil.
AB  - Epidemiological aspects of Babesia vogeli infection were studied in the canine
      population of a rural town located in the Brazilian "Drought Polygon" of the
      state of Minas Gerais, Brazil. The survey was carried out in March 2003, when 505
      dogs were identified and their characteristics registered on appropriate forms.
      Blood samples were collected at this time and again in June, September and
      December 2003. Serum samples were tested by the indirect fluorescent antibody
      test (IFAT) to detect antibodies against B. vogeli. The prevalence of anti-B.
      vogeli antibodies was 18.8%; however, no correlations were found between
      prevalence of infection and the age or gender of the animals. Cross-bred dogs
      presented a higher chance of acquiring infection in comparison to pure-bred dogs.
      Significant differences concerning the incidence of the disease were found during
      the period April-June in comparison to other months, demonstrating that
      transmission of B. vogeli is related to seasonal variations of tick infestations.
      The results indicate that climatic factors within the semiarid area interfere
      directly in the epidemiology of canine babesiosis.

PMID- 17210195
TI  - Membrane permeability of redox active metal chelators: an important element in
      reducing hydroxyl radical induced NAD+ depletion in neuronal cells.
AB  - There is substantial evidence implicating increased production of the hydroxyl
      radical and oxidative stress in the pathogenesis of neurodegenerative diseases
      such as Alzheimer's disease (AD). Significant amounts of hydroxyl radicals will
      be produced in the presence of hydrogen peroxide and redox active iron via Fenton
      chemistry. Increased iron levels within the cytoplasm of vulnerable neurons
      suggest that this may also be an important site of oxidative activity. We
      investigated the likelihood that intracellular, rather than extracellular
      chelation of ferrous or ferric iron may be more effective in reducing hydroxyl
      radical induced cell damage and preserving NAD(+) levels and cell viability.
      Using intracellular NAD(H) measurements as an indicator of cell viability we
      found that membrane permeable ferrous chelators were most efficient in preserving
      cellular NAD(+) levels. Hydrophilic, ferrous or ferric chelators and lipophilic
      ferric chelators were essentially ineffective in preventing cellular NAD(+)
      depletion when added at physiological concentrations. We propose that lipophilic
      ferrous chelators, due to their actions inside the cell, are effective agents for
      moderating neuronal damage in conditions such as AD where intracellular oxidative
      stress plays a significant role in disease pathology.

PMID- 17210196
TI  - Decreased Abeta secretion by cells expressing familial Alzheimer's disease-linked
      mutant presenilin 1.
AB  - Presenilin (PS) is a catalytic subunit of the gamma-secretase complex that
      cleaves the intramembranous region of amyloid precursor protein (APP), producing
      amyloid beta (Abeta) peptide. Familial Alzheimer's disease (FAD) results from PS
      mutations, which may alter gamma-secretase activity to enhance the production of
      highly aggregable Abeta42. The precise pathogenic effects of mutant PS remain
      unclear. To exclude the effects of endogenous PS, we established cell lines from
      PS1/PS2-deficient (PS-/-) fibroblasts capable of stably expressing either wild
      type (wt) PS1 or different mutant PS1s. Although both wt PS1 and mutant PS1
      formed gamma-secretase complexes of the same size and containing the same
      components, the amount of Abeta secreted by FAD mutant PS1-expressing cells was
      significantly reduced. The ratio of Abeta42 to Abeta40 (Abeta42/Abeta40) secreted
      by these cells, however, was significantly higher than that secreted by cells
      expressing wt PS1, which corroborated findings from a previous report. The
      elevated Abeta42/Abeta40 ratio observed with mutant PS1-expressing cells may be
      due to reduced Abeta40 production not increased Abeta42 production.

PMID- 17210197
TI  - A novel and simple biomolecules immobilization method: electro-deposition ZrO2
      doped with HRP for fabrication of hydrogen peroxide biosensor.
AB  - For the first time, a very novel and simple immobilization method for fabrication
      of hydrogen peroxide biosensor was reported in this paper. The biocompatible
      composite HRP-ZrO(2) thin films were synthesized on gold electrode surface based
      on electro-deposition zirconia doped with horseradish peroxidase (HRP) by cyclic
      voltammetry scanning in KCl solution containing ZrO(2) and HRP. The fabricated
      process of biosensor was characterized by electrochemical impedance spectroscopy
      (EIS) and the surface topography of the prepared films was imaged by atomic force
      microscope (AFM). The HRP in HRP-ZrO(2) thin films kept its bioactivity and
      exhibited excellent electrocatalytical response to the reduction of H(2)O(2).
      Experimental conditions influencing the biosensor performance such as pH,
      potential were optimized. The resulting biosensor (HRP-ZrO(2)/Au electrode)
      showed a linear response to H(2)O(2) over a concentration range from 0.02 to
      9.45mM with a detection limit of 2muM based on a signal-to-noise ratio of 3 under
      optimized conditions. The apparent Michaelis-Menten constant (K(M)(app)) was
      evaluated to be 8.01mM, which indicated the HRP in HRP-ZrO(2) thin films kept its
      native bioactivity and had high affinity for H(2)O(2). Moreover, the proposed
      biosensor showed high sensitivity, good reproducibility and long-term stability.
      What is more, this immobilization methodology widened biosensor application in
      biomolecules immobilization and could further develop for other protein and
      biomolecules immobilization.

PMID- 17210198
TI  - Characterization of the proteins of bacterial strain isolated from contaminated
      site involved in heavy metal resistance--a proteomic approach.
AB  - The present study describes response of a bacterial strain isolated from a
      polluted river to heavy metal toxicity. The bacterium was identified to be
      Klebsiella pneumoniae by biochemical tests using API 20E strips and 16S
      ribotyping. The isolate was studied for its tolerance to two heavy metals, i.e.,
      cobalt (Co(2+)) and lead (Pb(2+)) by growing it in citrate mineral medium (CMM).
      Proteomic approach involving two-dimensional polyacrylamide gel electrophoresis
      (2D PAGE) and mass spectrometry (MS) was used to identify the differentially
      expressed proteins under heavy metal stress. Two of the differentially expressed
      proteins were identified to be l-isoaspartate protein carboxymethyltransferase
      type II and DNA gyrase A. To our knowledge, this is for the first time that K.
      pneumoniae has been reported to be present in metal contaminated site and l
      isoaspartate protein carboxymethyltransferase type II protein to be over
      expressed under heavy metal stress. The role of these proteins in metal tolerance
      is discussed.

PMID- 17210199
TI  - HIV-1 matrix protein: a mysterious regulator of the viral life cycle.
AB  - Significant progress has been achieved in the last few years concerning the human
      immunodeficiency virus (HIV-1) life cycle, mostly in the fields of cellular
      receptors for the virus, virus assembly and budding of virus particles from the
      cell surface. Meanwhile, some aspects, such as postentry events, virus maturation
      and the regulatory role of individual viral proteins remain poorly defined. This
      review summarizes some recent findings concerning the role of Gag Pr55 and its
      proteolytic processing in the HIV-1 life cycle with particular emphasis on the
      functions of matrix protein p17 (MA), the protein which plays a key role in
      regulation of the early and late steps of viral morphogenesis. Based on our
      recent observations, the possibility is discussed that two subsets of MA exist,
      one cleaved from the Gag precursor in the host cell (cMA), and the other cleaved
      in the virions (vMA). It is suggested that two MA fractions possess diverse
      functions and are involved in different stages of virus morphogenesis as key
      regulators of the viral life cycle.

PMID- 17210200
TI  - Comparison of the endocytic properties of linear and branched PEIs, and cationic
      PAMAM dendrimers in B16f10 melanoma cells.
AB  - Many different polymers and architectures are now being developed as polymer
      therapeutics and non-viral vectors for cytosolic delivery, and cationic
      dendrimers, and linear and branched poly(ethylenimine)s (PEIs) have been widely
      used. For rational design and safe transfer into the clinic, it is important to
      better understand the cellular pharmacokinetics of the carrier, even if this will
      likely change when it is conjugated to, or complexed with, a targeting residue or
      therapeutic payload. The aim of these studies was to compare binding, endocytic
      capture and intracellular trafficking of linear and branched PEIs (Mw 25,000
      g/mol) and cationic PAMAM dendrimers (generations (gen) 2- 4) using B16F10 murine
      melanoma cells. FITC-dextran was used as a control for comparison. All polymers
      were first conjugated to Oregon Green (OG) and carefully characterised in respect
      of pH- and concentration-dependence of fluorescence. Throughout, non-toxic
      concentrations of polymer were used. Flow cytometry showed that all the cationic
      polymers were internalised by "adsorptive" endocytosis, with maximum uptake seen
      for PAMAM gen 4>>branched PEI>linear PEI>PAMAM gen 3>PAMAM gen 2. The PAMAM gen 4
      uptake rate was 130 fold greater than seen for FITC-dextran. Branched PEI had the
      highest extracellular binding (accounting for >50% of total cell-associated
      fluorescence) whereas for the linear PEI, binding was only 13% of the cell
      associated fluorescence. Unlike FITC-dextran, all cationic polymers lacked
      significant exocytosis over the time period studied. Whereas PAMAM gen 4 and the
      branched PEI were predominately internalised by cholesterol-dependent pathways,
      internalisation of linear PEI appeared to be independent of clathrin and
      cholesterol. A perception of the rate and mechanisms of cellular uptake of these
      vectors will be important in the context of their proposed use as drug delivery
      systems.

PMID- 17210201
TI  - External validation of the San Francisco Syncope Rule.
AB  - STUDY OBJECTIVE: We externally validate the ability of the San Francisco Syncope
      Rule to accurately identify syncope patients who will experience a 7-day serious
      clinical event. METHODS: Patients who presented to a single academic emergency
      department (ED) between 8 am and 10 pm with syncope or near-syncope were
      prospectively enrolled. Treating physicians recorded the presence or absence of
      all San Francisco Syncope Rule risk factors. Patients were contacted by telephone
      at 14 days for a structured interview. A 3-physician panel, blinded to the San
      Francisco Syncope Rule score, reviewed ED medical records, hospital records, and
      telephone interview forms to identify predefined serious clinical events. The
      primary outcome was the ability of the San Francisco Syncope Rule to predict any
      7-day serious clinical event. A secondary outcome was the ability of the San
      Francisco Syncope Rule to predict 7-day serious clinical events that were not
      identified during the initial ED evaluation. RESULTS: Of 592 eligible patients,
      477 (81%) provided informed consent. Direct telephone contact or
      admission/outpatient records were successfully obtained for 463 (97%) patients.
      There were 56 (12%) patients who had a serious 7-day clinical event, including 16
      (3%) who received a diagnosis after the initial ED evaluation. Sensitivity and
      specificity of the San Francisco Syncope Rule for the primary outcome were 89%
      (95% confidence interval [CI] 81% to 97%) and 42% (95% CI 37% to 48%),
      respectively, and 69% (95% CI 46% to 92%) and 42% (95% CI 37% to 48%),
      respectively, for the secondary outcome. Estimates of sensitivity were minimally
      affected by missing data and most optimistic assumptions for missing follow-up
      information. CONCLUSION: In this external validation cohort, the San Francisco
      Syncope Rule had a lower sensitivity and specificity than in previous reports.

PMID- 17210202
TI  - Identification of 90% of patients ultimately diagnosed with community-acquired
      pneumonia within four hours of emergency department arrival may not be feasible.
AB  - STUDY OBJECTIVE: We determine whether it is feasible to identify 90% of emergency
      department (ED) patients who subsequently receive a hospital discharge diagnosis
      of community-acquired pneumonia using the current Joint Commission on
      Accreditation of Healthcare Organizations (JCAHO)/Centers for Medicare and
      Medicaid Services (CMS) community-acquired pneumonia core measures criteria.
      METHODS: This was a retrospective case series in a university tertiary care ED.
      From a random sample of patients discharged from the hospital between January and
      December 2005 who were eligible for JCAHO/CMS community-acquired pneumonia
      antibiotic timing measure PN-5b, we identified the proportion of patients
      admitted through the ED who received antibiotics more than 4 hours after hospital
      arrival (outliers). Medical records of outliers were reviewed to determine
      whether they received a final ED community-acquired pneumonia diagnosis.
      Presenting characteristics of outliers with and without final ED community
      acquired pneumonia diagnoses were compared to determine feature(s) that might
      explain failure to diagnose community-acquired pneumonia in the ED. RESULTS: Of
      152 eligible ED community-acquired pneumonia patients, 53 (34.9%) were identified
      as outliers. Thirty-one of the outliers did not have a final ED community
      acquired pneumonia diagnosis. Thus, at least 20.4% (95% confidence interval [CI]
      14.3% to 27.7%) of all ED community-acquired pneumonia patients did not have an
      ED community-acquired pneumonia diagnosis. Of outliers without an ED community
      acquired pneumonia diagnosis, 43.3% had an abnormal chest radiograph compared
      with 95% with an ED community-acquired pneumonia diagnosis (odds ratio 24.8; 95%
      CI 3.63 to infinity). CONCLUSION: It may not be possible to identify 90% of
      hospitalized patients with a discharge diagnosis of community-acquired pneumonia
      during their ED assessment by using the current JCAHO/CMS criteria. It may
      therefore be unrealistic to expect that 90% of such patients will have
      antibiotics delivered within 4 hours of hospital presentation. A more realistic
      performance standard for antibiotic administration should be established or case
      definitions modified to include only patients with a final ED community-acquired
      pneumonia diagnosis or objective clinical and radiographic evidence.

PMID- 17210203
TI  - Applying the International Classification of Headache Disorders to the emergency
      department: an assessment of reproducibility and the frequency with which a
      unique diagnosis can be assigned to every acute headache presentation.
AB  - STUDY OBJECTIVE: Although almost 2 decades have passed since the International
      Headache Society first introduced its International Classification of Headache
      Disorders (ICHD), the applicability of this classification scheme in the
      emergency department (ED) has not been assessed. As a first step toward
      identifying the role the ICHD should play in the ED, we address 2 questions: Can
      a structured interview and adherence to the ICHD allow ED headache patients to be
      classified in a reproducible manner? With the ICHD, how often can one specific
      diagnosis be assigned to each ED headache presentation? METHODS: This was a
      structured interview and medical record review of patients with nontraumatic
      headache, performed in an urban ED from March 2004 through August 2005. Using the
      data from the interview and the subject's ED record, 2 emergency medicine
      investigators independently classified each of the headaches twice: first, to
      determine presence or absence of a primary headache disorder, and then to
      determine presence or absence of a secondary headache disorder. If a primary
      headache was present, it was further classified as migraine, tension-type
      headache, trigeminal autonomic cephalalgia, chronic daily headache, or primary
      headache unclassifiable. Interobserver discordance was adjudicated by an
      experienced headache specialist. RESULTS: Four hundred eighty patients were
      enrolled in the study. The emergency medicine investigators had a high level of
      interobserver agreement on secondary headaches (agreement 94% [95% confidence
      interval (CI) 92% to 96%]) and primary headaches (agreement 91% [95% CI 88% to
      93%]). Among the 480 subjects, 122 (25%) had a secondary headache disorder, 309
      (64%) had a primary headache disorder, 49 (10%) had a coexisting primary and
      secondary headache, and for 95 (20%) subjects, neither a primary nor a secondary
      headache could be diagnosed. Of 309 subjects with a primary headache, 186 (60%)
      had migraine, 34 (11%) had tension-type headache, 2 (1%) had trigeminal autonomic
      cephalalgia, and 77 (26%) had an unclassifiable primary headache. Overall, a
      specific ICHD headache diagnosis could not be assigned to 36% of subjects either
      because a specific primary headache disorder could not be identified or because
      neither a primary nor a secondary headache disorder could be diagnosed.
      CONCLUSION: Although a detailed structured interview in the ED and adherence to
      the ICHD resulted in reproducible classification of headache patients, more than
      one third of acute headache patients could not readily be given a specific ICHD
      diagnosis in the ED.

PMID- 17210204
TI  - Unanticipated death after discharge home from the emergency department.
AB  - STUDY OBJECTIVE: We measured the frequency of unanticipated death among patients
      discharged from the emergency department (ED) and reviewed these cases for
      patterns of potential preventable medical error. METHODS: This was a
      retrospective cohort of ED patients who were discharged to home from an urban
      tertiary-care facility after their evaluation, with subsequent case review.
      Subjects were aged 10 years and older, representing 387,334 visits among 186,859
      individuals, February 1994 through November 2004. The main outcome was mortality.
      Deaths were assessed for relatedness to the last ED visit, whether the death was
      expected, and whether there was possible medical error. Deaths that were
      unexpected and related to the ED visit were analyzed using grounded theory to
      identify common themes among these cases. Error cases were identified as a subset
      of this group. RESULTS: We identified and reviewed 117 patients, or 30.2 deaths
      within 7 days of discharge per 100,000 ED discharges home (95% confidence
      interval [CI] 25.2 to 36.2 deaths). Of the 117 cases, 58 (50%) were unexpected
      but related to the ED visit and 35 (60%) of these had a possible error. For the
      unexpected, related group, there were 15.0 deaths within 7 days per 100,000
      discharges home (95% CI 11.6 to 19.4 deaths); for the possible error group, there
      were 9.0 (95% CI 6.5 to 12.6 deaths). Four themes repeatedly emerged: atypical
      presentation of an unusual problem, chronic disease with decompensation, abnormal
      vital signs, and mental disability or psychiatric problem or substance abuse that
      may have made it less likely that the patient would return for worsening
      symptoms. CONCLUSION: Monitoring of death records can identify unanticipated
      deaths after health care encounters. Further hypothesis-driven research is needed
      to identify, prevent, or mitigate problems in care and reduce the rate of death
      after ED visit.

PMID- 17210205
TI  - Potential interference by hydroxocobalamin on cooximetry hemoglobin measurements
      during cyanide and smoke inhalation treatments.
AB  - STUDY OBJECTIVE: Concentrated aqueous solutions of hydroxocobalamin (OHCob) are
      administered intravenously for cyanide poisoning victims, many of whom also have
      concurrent smoke inhalation. Because of its intense light absorbance in visible
      wavelengths (absorption peak at 532 nm), we investigate potential interference
      effects of OHCob on total hemoglobin concentration (tHb), carboxyhemoglobin
      (COHb), methemoglobin (MetHb), and oxyhemoglobin (Hb-O2) cooximetry measurement
      values in blood. METHODS: In vivo cooximetry measurements were conducted with 3
      specific pathogen-free white New Zealand rabbits (3.80+/-0.21 kg) during the
      intravenous infusion of OHCob (625 mg during a 100-minute period). Resultant
      changes in tHb, Hb-O2, COHb, and MetHb values were measured and correlated with
      respect to estimated in vivo OHCob concentrations. In vitro measurements were
      conducted with rabbit blood to confirm in vivo measurements. RESULTS: The
      introduction of OHCob clearly interfered with the cooximetry measurements of each
      of the hemoglobin component fractions in whole blood and resulted in altered
      measurement values from the baseline values. The presence of OHCob in blood
      interferes with cooximetry measurements of COHb, MetHb, and Hb-O2. The increase
      in measured COHb fraction with increasing concentrations of OHCob was most
      notable. CONCLUSION: The presence of OHCob in blood interferes with cooximetry
      measurements of COHb, MetHb, and Hb-O2. These effects need to be considered
      during OHCob treatment of cyanide poisoning, particularly in smoke inhalation
      victims with potential for concurrent carbon monoxide exposure, because it may
      lead to potentially erroneous reported COHb levels.

PMID- 17210206
TI  - A prospective evaluation of shortened course oral N-acetylcysteine for the
      treatment of acute acetaminophen poisoning.
AB  - STUDY OBJECTIVE: Treatment with a shortened duration of oral N-acetylcysteine (20
      to 48 hours) after acute acetaminophen poisoning is effective in the prevention
      of subsequent hepatic failure and death when administered to individuals meeting
      appropriate laboratory criteria. METHODS: Individuals with a potentially toxic
      acetaminophen ingestion according to serum acetaminophen levels were identified
      prospectively using a large statewide poison control system database throughout a
      12-month period. N-acetylcysteine was administered for a minimum of 6 doses (20
      hours), after which laboratory studies were obtained. Discontinuation of N
      acetylcysteine was recommended by the poison center when 2 criteria were met:
      serum acetaminophen was undetectable (<10 microg/mL) and liver test results were
      normal (serum aminotransferase, international normalized ratio). A follow-up
      questionnaire was administered to individuals treated with N-acetylcysteine for
      48 hours or less to ascertain the presence of symptoms consistent with
      progressive hepatotoxicity. RESULTS: Of 205 acutely poisoned individuals treated
      with N-acetylcysteine for 48 hours or less, 195 were successfully contacted after
      discharge, and 187 of 195 (95.9%) reported no symptoms consistent with hepatic
      failure. Eight individuals (4.1%) reported abdominal pain or vomiting; however,
      none received further N-acetylcysteine treatment or additional hospitalization.
      CONCLUSION: A shortened duration of treatment with N-acetylcysteine (20 to 48
      hours) may be an effective treatment option in individuals considered to be at no
      further risk of developing liver toxicity according to the fulfillment of
      appropriate laboratory criteria before N-acetylcysteine discontinuation.

PMID- 17210207
TI  - Evaluation of a modified prediction instrument to identify significant pediatric
      intracranial injury after blunt head trauma.
AB  - STUDY OBJECTIVE: We evaluate the effect of a modification of the University of
      California-Davis Pediatric Head Injury Rule on the ability of the decision
      instrument for pediatric head injury to predict clinically important intracranial
      injury in an external cohort. METHODS: We analyzed data prospectively recorded in
      1,666 pediatric patients enrolled in the derivation set of the National Emergency
      X-Radiography Utilization Study II (NEXUS II). Treating physicians at 21
      emergency departments recorded the presence or absence of clinical predictors on
      all patients who received a head computed tomography (CT) scan after experiencing
      blunt head trauma. Predictors included 3 exact elements of the University of
      California-Davis Rule (abnormal mental status, signs of skull fracture, and scalp
      hematoma in children < or = 2 years of age), some with different wording, and 2
      modified elements with new definitions (the presence of high-risk vomiting or
      severe headache, rather than any vomiting or headache). RESULTS: A significant
      intracranial injury was identified by CT in 138 (8.3%) patients. Sensitivity of
      the modified instrument to detect significant intracranial injury was 90.4% (95%
      confidence interval [CI] 85.4% to 95.4%); 13 children with such an injury were
      misclassified as low risk. Specificity of the modified instrument was 42.7% (95%
      CI 40.1% to 45.3%). CONCLUSION: In the NEXUS II cohort, a modified version of the
      University of California-Davis Rule misclassified a substantial proportion of
      pediatric patients with clinically important blunt head injury. Although we
      cannot evaluate the exact University of California-Davis Rule, we demonstrate
      that using stricter definitions of "headache" and "vomiting" and different
      wording than in the original study may have unintended or negative consequences.
      We emphasize the importance of careful attention to precise definitions of
      clinical predictors when a decision instrument is used.

PMID- 17210208
TI  - A randomized controlled trial comparing a fascia iliaca compartment nerve block
      to a traditional systemic analgesic for femur fractures in a pediatric emergency
      department.
AB  - STUDY OBJECTIVE: We determine whether a fascia iliaca compartment nerve block can
      provide superior pain management compared with intravenous morphine sulfate for
      the initial pain management of femur fracture patients presenting to a pediatric
      emergency department. The primary outcome measured is pain scores; a difference
      of 15% in scores assessed at 30 minutes from the study's baseline pain management
      is considered clinically meaningful. Secondary outcomes include the duration of
      analgesia, the need for additional medications, adverse events, nerve block
      complications, and satisfaction scores. METHODS: This was a prospective,
      randomized, unblinded, controlled trial conducted on children aged 15 months to
      18 years with acute femur fractures, presenting to a free-standing, tertiary care
      children's hospital. Patients were randomized to receive intravenous morphine
      sulfate or a fascia iliaca compartment nerve block using ropivacaine (Naropin).
      Pain scores (Children's Hospital of Eastern Ontario Pain Scale [CHEOPS]; Face,
      Legs, Activity, Cry and Consolability Pain Scale; Faces Pain Scale) were recorded
      at initial analgesic administration (baseline), at 5, 10, 15, 30, and 60 minutes,
      and then hourly up to 6 hours from baseline by trained nursing observers and
      research assistants. RESULTS: Fifty-five patients, 26 in the fascia iliaca
      compartment nerve block group and 29 in the morphine sulfate group, ranged in age
      from 16 months to 15 years (median 5.7 years). Baseline mean CHEOPS scores were
      similar: 9.4 fascia iliaca compartment nerve block and 9.5 morphine sulfate. Mean
      CHEOPS scores at 30 minutes after initial treatment were 5.87 for fascia iliaca
      compartment nerve block and 7.54 for morphine sulfate, with a difference of 1.67,
      which corresponds to an 18% (95% confidence interval [CI] 8% to 27%) difference
      in pain reduction between the 2 groups, according to the average baseline score
      of 9.45. Similar lower pain scores were observed in the fascia iliaca compartment
      nerve block group as early as 10 minutes from baseline and throughout the 6-hour
      duration of the study. In comparing the entire 6-hour CHEOPS pain scores,
      patients who received a fascia iliaca compartment nerve block showed lower scores
      by approximately 15% (95% CI 6% to 24%) compared to patients who received
      morphine sulfate. Median duration of analgesia was longer in the fascia iliaca
      compartment nerve block group compared with that in the morphine sulfate group
      (313 minutes [95% CI 154 to 360 minutes] versus 60 minutes [95% CI 10 to 255
      minutes]). Fewer additional medications were given to patients who received the
      fascia iliaca compartment nerve block. No complications from the nerve block
      occurred. Satisfaction scores were higher with the fascia iliaca compartment
      nerve block among the medical staff. CONCLUSION: Fascia iliaca compartment nerve
      block provided clinically superior pain management compared with intravenous
      morphine sulfate at 30 minutes from baseline and throughout the initial 6 hours
      of medical treatment of children 16 months to 15 years who had isolated acute
      femur fractures. The results of this study, however, may be inflated by the
      nonblinding of the pain observers. Despite this potential bias, the fascia iliaca
      compartment nerve block should be considered as a valuable procedure in managing
      the pain commonly observed in these injured children.

PMID- 17210209
TI  - The on-call crisis: a statewide assessment of the costs of providing on-call
      specialist coverage.
AB  - STUDY OBJECTIVE: A recent change in the delivery of emergency care is a growing
      reluctance of specialists to take call. The objective of this study is to survey
      Oregon hospitals about the prevalence and magnitude of stipends for taking
      emergency call and to assess the ways in which hospitals are limiting services.
      METHODS: This was a cross-sectional, standardized survey of chief executive
      officers from all hospitals with emergency departments in Oregon (N=56). This e
      mail-based survey asked about payments made to specialists to take call and
      examined changes in hospitals' trauma designation and ability to provide
      continuous coverage for certain specialties. RESULTS: We received responses from
      54 of 56 hospitals, representing a 96% response rate (100% of trauma centers).
      Twenty-three of 54 (43%) Oregon hospitals pay a stipend to at least 1 specialty,
      and 17 (31%) hospitals guarantee pay for uninsured patients treated on call.
      Stipends ranged from $300 per month to more than $3,000 per night, with a median
      stipend of $1,000 per night to take call. Trauma surgeons, neurosurgeons, and
      orthopedists were the specialists most likely to receive stipends. Seven of 54
      (13%) hospitals have had their trauma designation affected by on-call issues.
      Twenty-six hospitals (48%) have lost the ability to provide continuous coverage
      for at least 1 specialty. CONCLUSION: Problems with on-call coverage are
      prevalent in Oregon and affect hospital financing and delivery of services. A
      continuation of the current situation could degrade the effectiveness of the
      trauma system and adversely affect the quality of emergency care.

PMID- 17210210
TI  - The role of peptide YY in regulating glucose homeostasis.
AB  - The gut-derived hormone peptide YY (PYY) is most commonly known for its effect on
      satiety, decreasing food intake and body weight in animals and humans. However,
      PYY is also involved in a wide range of digestive functions including regulating
      insulin secretion and glucose homeostasis. Over the last few years, there have
      been several interesting clinical and animal studies investigating the role of
      PYY in glucose homeostasis. This review aims to present an updated summary of
      findings over the last few decades highlighting the role of PYY in regulating
      insulin output and insulin sensitivity, and the potential mechanisms involved.

PMID- 17210211
TI  - WITHDRAWN: Use of platelet rich plasma (PRP) in the reconstruction of mandibular
      bony defects: Clinical and radiographic follow-up.
AB  - PURPOSE OF THE STUDY: The purpose of the study was to evaluate the effect of
      adding platelet rich plasma (PRP) to a particulate autogenous bone graft in the
      healing of bony defects following ablative surgery to resect malignancies of the
      mandible. MATERIAL AND METHODS: Ten patients, who underwent curative surgical
      therapy for a malignant tumour and who needed reconstruction of the body of the
      mandible were selected for this study. The patients were randomly divided into
      two groups of five patients. In the first group, the defect was reconstructed
      using an autogenous free bone graft taken from the anterior iliac crest. The five
      patients in the second group underwent the same treatment, except that the bone
      graft was mixed with platelet rich plasma (PRP). Panoramic radiographs were taken
      immediately, at 1 month, 3 months and at 9 months intervals, after
      reconstruction. Radiographic evaluation took place in a standardized way by two
      independent examiners. RESULTS: The clinical outcome of the surgical
      reconstruction was satisfactory. The initial bone healing in all patients was
      uneventful. The postoperative successive radiographs showed adequate
      consolidation of the bone in all cases. Bone healing, as manifested by the
      obliteration of the bone gaps at the osteotomy sites, was particularly present in
      the PRP group at 3 months period. This was found to be statistically significant
      (Chi-square test, P<0.05). CONCLUSION: The use of PRP appeared to enhance bone
      healing considerably. PRP and autogenous free bone grafts might have a potential
      for routine clinical use to reconstruct bony defects.

PMID- 17210212
TI  - Spine stability: the six blind men and the elephant.
AB  - Stability is one of the most fundamental concepts to characterize and evaluate
      any system. This term is often ambiguously used in spinal biomechanics. Confusion
      arises when the static analyses of stability are used to study dynamic systems
      such as the spine. Therefore, the purpose of this paper is to establish a common
      ground of understanding, using standard, well-defined terms to frame future
      discussions regarding spine dynamics, stability, and injury. A qualitative
      definition of stability, applicable to dynamic systems, is presented. Additional
      terms, such as robustness (which is often confused with stability) and
      performance are also defined. The importance of feedback control in maintaining
      stability is discussed. Finally, these concepts are applied to understand low
      back pain and risk of injury.

PMID- 17210213
TI  - A biomechanical analysis of the effect of lateral column lengthening calcaneal
      osteotomy on the flat foot.
AB  - BACKGROUND: Biomechanical models have been used to study the plantar aponeurosis,
      medial arch height, subtalar motion, medial displacement calcaneal osteotomy,
      subtalar arthroereisis and the distribution of forces in the normal and flat
      foot. The objective was to examine the hypothesis that increased load on the
      medial arch in the adult flat foot can be reduced through a 10mm lateral column
      lengthening calcaneal osteotomy 10 mm proximal from the calcaneal cuboid joint.
      METHODS: A three dimensional multisegment biomechanical model was used with
      anatomical data from a normal foot, a flat foot and a foot corrected with a 10mm
      lateral column lengthening calcaneal osteotomy. The response of a normal foot, a
      flat foot and a flat foot with a 10mm lateral column lengthening calcaneal
      osteotomy to an applied load of 683 N was analyzed using the biomechanical model.
      Data for the biomechanical model was obtained from a cadaver foot using the
      direct linear transformation method. Direct linear transformation uses multiple
      cameras to determine the spatial location of anatomical landmarks. FINDINGS: Load
      on the first metatarsal increases to 37% body weight in the flat foot compared to
      12% for the normal foot and the moment about the talo-navicular joint increases
      from 5.6 N m to 21.6 N m. Lateral column lengthening shifts the load toward the
      lateral column, decreasing load on the first metatarsal to 10% and decreasing the
      moment about the talo-navicular joint to 8.1 N m. INTERPRETATION: The analysis
      shows that a 10mm lateral column lengthening calcaneal osteotomy reduces the
      excess force on the medial arch in an adult flat foot and adds biomechanical
      rationale to this clinical procedure.

PMID- 17210214
TI  - Zingiber officinale Roscoe alone and in combination with alpha-tocopherol protect
      the kidney against cisplatin-induced acute renal failure.
AB  - Oxidative stress due to abnormal production of reactive oxygen molecules (ROM) is
      believed to be involved in the etiology of toxicities of many xenobiotics.
      Evidences suggested that ROM is involved in the nephrotoxicity of a widely used
      synthetic anticancer drug cisplatin. The nephroprotective effects of ethanol
      extract of Zingiber officinale alone and in combination with vitamin E (alpha
      tocopherol) were evaluated using cisplatin (single dose of 10 mg/kg body wt, i.p)
      induced acute renal damage in mice. The results of the study indicated that Z.
      officinale significantly and dose dependently protected the nephrotoxicity
      induced by cisplatin. The serum urea and creatinine levels in the cisplatin alone
      treated group were significantly elevated (P<0.01) with respect to normal group
      of animals. The levels were reduced in the Z. officinale (250 and 500 mg/kg, p.o)
      plus cisplatin, vitamin E (250 mg/kg) plus cisplatin, and Z. officinale (250
      mg/kg) with vitamin E plus vitamin E treated groups. The renal antioxidant
      enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx) activities and level of reduced glutathione (GSH) were declined;
      level of malondialdehyde (MDA) was elevated in the cisplatin alone treated group.
      The activities of SOD, CAT GPx and level of GSH were elevated and level of MDA
      declined significantly (P<0.05) in the Z. officinale (250 and 500 mg/kg) plus
      cisplatin and Z. officinale (250 mg/kg) with vitamin E plus cisplatin treated
      groups. The protective effect of Z. officinale (250 mg/kg body wt) was found to
      be better than that of vitamin E (250 mg/kg body wt). The results also
      demonstrated that combination of Z. officinale (250 mg/kg) with vitamin E (250
      mg/kg) showed a better protection compared to their 250 mg/kg alone treated
      groups. This study concluded that ethanol extract of Z. officinale alone and in
      combination with vitamin E partially ameliorated cisplatin-induced
      nephrotoxicity. This protection is mediated either by preventing the cisplatin
      induced decline of renal antioxidant defense system or by their direct free
      radical scavenging activity.

PMID- 17210215
TI  - Pro-inflammatory cytokines in stable chronic alcoholics: relationship with fat
      and lean mass.
AB  - Cytokines are mediators of the inflammatory response, secreted by many tissues,
      including adipocytes. Chronic alcoholic liver disease and alcoholic hepatitis are
      associated with elevated serum cytokine levels which yield prognostic value in
      this situation. Most studies have been performed in patients with acute alcoholic
      hepatitis. However, cytokine alterations in stable alcoholics have been less
      studied, as is also the case for the relationship between cytokines and fat and
      lean mass in these patients. The aim of the present study was to analyse the
      relationships between some proinflammatory serum cytokine levels and lean mass,
      fat mass, nutritional status, and liver function parameters in stable alcoholic
      patients. We determined serum TNF-alpha, interleukin (IL)-6, IL-8 and TNF
      receptor 2 (TNFr2) in 77 male alcoholic patients in a stable phase (before
      hospital discharge). In all patients we performed a total-body composition
      analysis (Hologic DEXA), nutritional assessment including body mass index,
      triceps skinfold, brachial perimeter, and assessment of liver function. Forty-two
      healthy volunteer health workers served as controls. IL-8, TNF-alpha and TNFr2
      were significantly higher in patients than in controls. No differences were
      observed between patients and controls regarding fat mass, but alcoholics showed
      significantly decreased lean mass than controls. Only IL-6 was significantly
      related with body fat in patients with elevated IL-6 levels. Poor relationships
      were observed between lean mass and cytokines; some nutritional parameters showed
      inverse relationships with serum TNF, whereas TNF and IL-8 were inversely related
      with albumin and prothrombin activity. Thus, cytokine levels were elevated in
      stable alcoholic patients, and IL-6 levels showed significant correlation with
      body fat mass, raising the possibility that adipose tissue contributes to the
      persistence of high levels of cytokines in stable alcoholics.

PMID- 17210216
TI  - The role of toxicokinetics in xylene-induced ototoxicity in the rat and guinea
      pig.
AB  - In the rat, some aromatic solvents cause a high level of ototoxicity that is
      characterized by damage to outer hair cells in the cochlea, which results in
      irreversible hearing loss. However, there is a vast difference in their potency.
      Among the three isomers of xylene, only para-xylene has been shown to be ototoxic
      in the rat. Moreover, all the species do not show the same susceptibility to
      ototoxic solvents, the rat being the most susceptible and the guinea pig seeming
      resistant to this ototoxic effect. The objective of the study was to determine
      whether toxicokinetic factors could explain the differences in ototoxicity
      observed among the three isomers of xylene in the rat and the species-dependent
      ototoxicity in the rat and the guinea pig. Blood and brain concentrations of each
      isomer were monitored in Sprague-Dawley rats treated orally by gastric intubation
      with a single dose or a 10 day-repeated treatment of 8.47 mmol/kg (an ototoxic
      dosage for para-xylene) of each isomer. Moreover, histology of the cochlea was
      carried out and the toxicokinetics of meta-xylene was monitored in rats treated
      with a single dose or a 10 day-repeated treatment of 16.94 mmol/kg meta-xylene, a
      non-ototoxic isomer. Similarly, histology of the cochlea was carried out and the
      toxicokinetics of para-xylene was followed in guinea pigs treated by gavage with
      a single dose or a 10 day-repeated treatment of 8.47 mmol/kg para-xylene.
      Finally, the blood and brain concentrations of para-xylene were measured in both
      the rats and the guinea pigs after a 4-h exposure to 1800 ppm of para-xylene.
      Among the three isomers studied, para-xylene yielded the highest blood and brain
      concentrations in the acutely and repeatedly exposed rats. When given a high
      dosage of meta-xylene (16.94 mmol/kg), the rats showed blood and brain
      concentrations of meta-xylene in the same order as those obtained with 8.47
      mmol/kg para-xylene, but no outer hair cell loss was observed. No outer hair cell
      loss was observed in the guinea pigs treated with para-xylene. Whatever the
      exposure pattern, the blood and brain concentrations of para-xylene in the rats
      were 3.1-9.5 times higher than those measured in the guinea pigs. These results
      indicate that toxicokinetic factors cannot explain the differences in ototoxicity
      observed with the three isomers in the rat. However, they suggest that the
      differences in susceptibility to para-xylene observed between the rats and the
      guinea pigs might be due to toxicokinetic factors.

PMID- 17210218
TI  - Endometriosis, dysmenorrhea and diet--what is the evidence?
AB  - The objective of this study is to assess the literature concerning the effect of
      diet on endometriosis and dysmenorrhea and to elucidate evidential support, to
      give dietary recommendations to women suffering from these conditions. A
      systematic search in electronic databases on a relationship between diet and
      endometriosis/dysmenorrhea was performed. Data on diet and endometriosis were
      limited to four trials of which two were animal studies. The articles concerning
      human consumption found some relation between disease and low intake of vegetable
      and fruit and high intake of vegetarian polyunsaturated fat, ham, beef and other
      red meat. Results concerning fish intake were not consistent. Eight trials of
      different design, with a total of 1097 women, investigated the relationship
      between diet and dysmenorrhea. Intake of fish oil seemed to have a positive
      effect on pain symptoms. This study concludes that literature on diet and
      endometriosis is sparse, whereas eight studies have looked at diet and
      dysmenorrhea. No clear recommendations on what diet to eat or refrain from to
      reduce the symptoms of endometriosis can be given, while a few studies indicate
      that fish oil can reduce dysmenorrhea. Further research is recommended on both
      subjects.

PMID- 17210217
TI  - Cell death and cytotoxic effects in YAC-1 lymphoma cells following exposure to
      various forms of mercury.
AB  - The effects of 1 min-4 h exposures to four Hg compounds (mercuric chloride
      [HgCl2], methyl mercuric chloride [CH3HgCl], p-chloromercuribenzoate [p-CMB] and
      thimerosal [TMS; ethylmercurithiosalicylate]) on cell death, microtubules, actin,
      CD3 receptor expression, protein tyrosine phosphorylation (PTyr-P) and
      intracellular calcium ([Ca2+]i) levels were investigated in YAC-1 lymphoma cells
      using flow cytometry. YOPRO-1 (YP) and propidium iodide (PI) dye uptake indicated
      all forms of Hg tested were toxic at concentrations ranging from 25.8-48.4
      microM, with two distinct patterns of effects. Early apoptosis was prolonged for
      CH3HgCl- and TMS-treated cells, with more than 50% remaining YP+/PI- after 4h.
      Both CH3HgCl and TMS induced complete loss of beta-tubulin fluorescence,
      indicative of microtubule depolymerization and inhibition of tubulin synthesis
      and/or beta-tubulin degradation, while F-actin fluorescence diminished to a
      lesser degree and only after loss beta-tubulin. CH3HgCl and TMS induced an almost
      immediate two-fold increase in CD3 fluorescence, with levels returning to
      baseline within minutes. With continued exposure, CD3 fluorescence was reduced to
      approximately 50% of baseline values. Both compounds also increased PTyr-P two-
      to three-fold immediately, with levels returning to baseline at 4h. Similarly,
      two- to three-fold increases in [Ca2+]i were noted after 1 min exposure. [Ca2+]i
      increased progressively, reaching levels five- to eight-fold greater than control
      values. In contrast, dye uptake was delayed with HgCl2 and p-CMB, although cell
      death proceeded rapidly, with almost all non-viable cells being late apoptotic
      (YP+/PI+) by 4h. p-CMB produced early reductions in F-actin, and after 4h,
      complete loss of F-actin with only partial reduction of total beta-tubulin was
      seen with both p-CMB and HgCl2. HgCl2 reduced CD3 expression and PTyr-P slightly
      within minutes, while p-CMB produced similar effects on CD3 only at 4h, at which
      time PTyr-P was increased two- to three-fold. Both compounds increased [Ca2+]i
      within minutes, though levels remained under twice the baseline concentration
      after 15 min exposure. With continued exposure, [Ca2+]i increased to levels two-
      to five-fold greater than control values. These findings indicate the two groups
      of Hg compounds may induce cell death by distinct pathways, reflecting
      interactions with different cellular targets leading to cell death.

PMID- 17210219
TI  - Screening history of women in Malmo with invasive cervical cancer.
AB  - OBJECTIVES: Cervical cancer is one of the most common forms of cancer among
      women. Cytological screening and follow-up are potentially effective procedures
      for preventing the development of - and mortality from - cervical cancer. The
      purpose of this study was to investigate the screening history of women diagnosed
      with cervical cancer with the aim of improving the screening programme. STUDY
      DESIGN: All of the 187 women diagnosed with invasive cervical cancer in Malmo
      between 1991 and 2000 were identified, and those below 61 years of age (n=130)
      were included in the analysis. The cytological and histological screening history
      of these women prior to their diagnosis was scrutinized. We analyzed shortcomings
      related to the cervical screening with special attention to participation defined
      as having had a cervical smear within 1 year of the scheduled time. RESULTS: Of
      the non-participants who developed cervical cancer (n=70), roughly one-third
      "never participated," half were "sub-optimal participants," and one-sixth were
      "decliners," i.e., women who declined the recommended measures. Among
      participants (n=60), 80% were either "unexplained" (n=35) or "misread as normal"
      (n=13). The 9.5% subgroup of non-participants was at an 11-fold increased risk of
      being diagnosed with invasive cervical cancer. CONCLUSION: The greatest reduction
      in cervical cancer would be realized if non-participants could be brought into
      the screening program.

PMID- 17210220
TI  - Ultrasound evaluation of dynamic responses of female pelvic floor muscles.
AB  - Ultrasound imaging of the pelvic floor carries diagnostically important
      information about the dynamic response of the pelvic floor muscles (PFM) to
      potentially incontinence-producing stress, which cannot be readily captured and
      assimilated by the observer during the scanning process. We presented an approach
      based on motion tracking quantitatively to analyze the dynamic parameters of PFM
      on the ano-rectal angle (ARA). Perineal ultrasonography was performed on 22
      asymptomatic females and nine stress urinary incontinent (SUI) patients with a
      broad age distribution and parity. The ventral-dorsal and cephalad-caudad
      movements of the ARA were resolved and kinematic parameters, in terms of
      displacement, trajectory, velocity and acceleration, were analyzed. The results
      revealed the possible mechanisms of PFM responses to prevent the urine from
      incontinence in fast and stress events such as coughs. The statistical analyses
      showed that the PFM responses of the healthy subjects and the SUI patients are
      significantly different in both the supine and standing experiments.

PMID- 17210221
TI  - DAX1: Increasing complexity in the roles of this novel nuclear receptor.
AB  - DAX1 (NR0B1) is a nuclear receptor with a characteristic C-terminal ligand
      binding domain, but an atypical DNA binding domain. Mutations in the DAX1 gene
      cause adrenal hypoplasia congenita (AHC) establishing its biological importance.
      Recent studies highlight the complexities of DAX1 regulation and function. There
      is considerable phenotypic variability in AHC suggesting the existence of DAX1
      modifier genes and environmental influences on DAX1 function. The findings of an
      alternatively spliced DAX1A, more common than DAX1 in all tissues except testis,
      of DAX1 homodimers, and of DAX1 heterodimers with a number of transcription
      factor partners including DAX1A and SHP point to an expanded transcription
      regulatory network under DAX1 control. Model organisms (mice and zebrafish) are
      being used to identify other DAX1 functions and modifier genes to understand the
      pathogenesis of AHC and the lack of genotype-phenotype correlation.

PMID- 17210222
TI  - Roles of the LHX3 and LHX4 LIM-homeodomain factors in pituitary development.
AB  - The LHX3 and LHX4 LIM-homeodomain transcription factors play essential roles in
      pituitary gland and nervous system development. Mutations in the genes encoding
      these regulatory proteins are associated with combined hormone deficiency
      diseases in humans and animal models. Patients with these diseases have complex
      syndromes involving short stature, and reproductive and metabolic disorders.
      Analyses of the features of these diseases and the biochemical properties of the
      LHX3 and LHX4 proteins will facilitate a better understanding of the molecular
      pathways that regulate the development of the specialized hormone-secreting cells
      of the mammalian anterior pituitary gland.

PMID- 17210223
TI  - Dephosphorylation of TORC initiates expression of the StAR gene.
AB  - Cyclic AMP responsive element (CRE) binding protein (CREB) is known to activate
      transcription when its Ser133 is phosphorylated. However, transducer of regulated
      CREB activity (TORC), a CREB specific co-activator, upregulates CREB activity in
      a phospho-Ser133-independent manner. Interestingly, TORC is also regulated by
      phosphorylation; the phospho-form is inactive, and the dephospho-form active.
      When PKA phosphorylates CREB, it inhibits TORC kinases simultaneously and
      accelerates dephosphorylation of TORC. We show in this report that staurosporine,
      a kinase inhibitor, induces the expression of the StAR gene in Y1 adrenocortical
      cells, possibly a result of an increase in the population of dephospho-TORC. The
      expression of the StAR gene is known to be regulated by SF-1 and CREB, and the co
      activators CBP/p300 may mediate the actions of both factors. Our experiments
      using KG501, a disruptor of the interaction between phospho-CREB and CBP/p300,
      also support the importance of TORC in the regulation of StAR gene expression.

PMID- 17210224
TI  - Octreotide induces apoptosis in the oxyntic mucosa.
AB  - Previous studies show that octreotide LAR causes regression of gastric ECL-cell
      carcinoids, reducing both number and size of tumours. This study examines the
      molecular mechanisms behind the antiproliferative effect of octreotide on the
      oxyntic mucosa. Female rats received octreotide LAR for 21 days. Serum gastrin
      was measured and tissue samples for RNA extraction and histology collected from
      the oxyntic mucosa. Affymetrix analysis showed regulated genes related to
      apoptosis and proliferation, and a large group of regulated growth-related
      transcription factors. Verification by real time qRT-PCR showed a high degree of
      consistency to the microarray results. Supporting the molecular results,
      histomorphometry showed significant decreases in the number of gastric glands,
      cells per gland and length of glands, and a tendency towards increased apoptosis
      and decreased proliferation. Thus, octreotide exerts a negative effect on oxyntic
      mucosal growth, and induces extensive gene expression changes relevant to growth
      regulation.

PMID- 17210225
TI  - Expression of TAG-72 in ovarian cancer and its correlation with tumor stage and
      patient prognosis.
AB  - Tumor associated glycoprotein-72 (TAG-72), a pancarcinoma antigen, was initially
      identified in cancer tissues by its immunoreactivity to a monoclonal antibody
      B72.3. In this study, we have analyzed the expression and localization profiles
      of TAG-72 in ovarian cancer tissue samples of different stages and histological
      subtypes by immunohistochemistry using a second generation high affinity
      monoclonal antibody CC49. We have also studied the expression of TAG-72 in
      ovarian cancer cell lines by confocal microscopy and immunoblot analyses. A
      correlation between TAG-72 expression and localization with patients' prognosis
      was also analyzed using Kaplan-Meier analysis. Eighty eight percent of the
      ovarian cancer tissue samples (n=43) showed immunoreactivity with CC49 antibody.
      The expression of TAG-72 in advanced stage cancer tissues (mean composite
      score=3.7) was significantly higher (p=0.035) compared to the early stage tumors
      (mean composite score=2.3). However, no significant correlation of TAG-72 was
      observed with histological tumor types. A marginal correlation of TAG-72 staining
      with patients' survival was observed. Interestingly, the membrane localization of
      TAG-72 in tumors was significantly (p=0.0082) associated to the poor clinical
      outcome, while cytoplasmic staining was correlated significantly to a better
      prognosis (p=0.0051). Immunoblot analysis demonstrated the expression of TAG-72
      in three ovarian cancer cell lines (OVCAR3, SB247 and COV362.4). In conclusion,
      the tumor-specific expression of TAG-72 and its association with disease stage
      indicate its potential as a marker for effective disease management and targeted
      cancer therapy.

PMID- 17210226
TI  - Five-year experience of a burn survivor's position as a member of the burn team
      at a regional burn center.

PMID- 17210227
TI  - Analysis of prognostic indexes and other parameters to predict the length of
      hospitalization in thermally burned patients.
AB  - BACKGROUND: In a retrospective study the influence of several clinical data and
      prognostic indexes on the length of hospital stay in burned patients was
      investigated. METHODS: We recorded all admitted patients from January 2004 to
      December 2005 except for electrical and chemical injuries or patients that died
      during recovery. Age, gender, weight, height, body surface area, fluid, caloric
      and protein delivery, Total Burn Surface Area, full thickness burn surface area,
      Roi index, Baux score, Unit Burn Standard index, Abbreviated Burn Severity Index
      and the length of hospitalization were registered. A univariate and multivariate
      analysis was performed to look for correlations between these parameters and the
      length of hospitalization. RESULTS: We recorded eligible 233 patients. The
      univariate analysis showed that age, protein and caloric delivery, Roi index and
      ABSI were significantly related with the length of hospitalization while, at the
      multivariate analysis, only Roi index was related (p<0.05). However, Roi index
      was able to predict only 5.5-6% of cases. CONCLUSIONS: A correlation exists
      between the length of hospital stays and the Roi index in burned patients but
      does not explain the bulk of evidence. Further studies are required to
      investigate this relation, to screen other parameters and to correlate them with
      measures of outcome, i.e. functional (the range of motion of articulations) or
      aesthetic (patient's self assessment of his body image).

PMID- 17210228
TI  - Novel therapeutic targets in lung cancer: Inhibitor of apoptosis proteins from
      laboratory to clinic.
AB  - Lung cancer is the leading cause of cancer death worldwide. Despite the
      introduction of new agents and schedules, chemotherapy still obtains
      unsatisfactory overall response rates, rare complete remissions and responses of
      relatively short duration. The inhibitor of apoptosis proteins (IAPS) are a
      family of caspase inhibitors that selectively bind and inhibit caspases-3, -7,
      and -9. As caspase activation is central to apoptosis, novel therapeutic drugs
      that target IAPs enabling apoptosis to occur have potential as a treatment of
      malignancy. Several agents that target core components of the apoptotic
      signalling pathway are currently at an early stage of development. This review
      reports the progress being made in characterising the IAP family, with a focus on
      the available data relevant to the treatment of lung cancer.

PMID- 17210229
TI  - Postnatal development of cannabinoid receptor type 1 expression in rodent
      somatosensory cortex.
AB  - Endocannabinoids are powerful modulators of synaptic transmission that act on
      presynaptic cannabinoid receptors. Cannabinoid receptor type 1 (CB1) is the
      dominant receptor in the CNS, and is present in many brain regions, including
      sensory cortex. To investigate the potential role of CB1 receptors in cortical
      development, we examined the developmental expression of CB1 in rodent primary
      somatosensory (barrel) cortex, using immunohistochemistry with a CB1-specific
      antibody. We found that before postnatal day (P) 6, CB1 receptor staining was
      present exclusively in the cortical white matter, and that CB1 staining appeared
      in the gray matter between P6 and P20 in a specific laminar pattern. CB1 staining
      was confined to axons, and was most prominent in cortical layers 2/3, 5a, and 6.
      CB1 null (-/-) mice showed altered anatomical barrel maps in layer 4, with
      enlarged inter-barrel septa, but normal barrel size. These results indicate that
      CB1 receptors are present in early postnatal development and influence
      development of sensory maps.

PMID- 17210230
TI  - Early initiation of substance use and subsequent risk factors related to suicide
      among urban high school students.
AB  - OBJECTIVE: To examine the association between onset of substance use and risk
      factors related to suicide. METHOD: 1252 adolescents in two urban school
      districts completed surveys as part of a large, randomized controlled prevention
      effectiveness trial. Risk factors measured included depressive symptoms, suicide
      ideation, suicide ideation specifically with alcohol and/or drug use, endorsement
      of suicide as a personal option, and suicide attempt. RESULTS: In our final
      multivariate models that controlled for current substance use and demographic
      characteristics, we found that earlier onset of hard drug use among boys was
      associated with all five suicide risk factors. In comparison, among girls,
      earlier onset of regular cigarette smoking, getting drunk, and hard drug use was
      associated with some of suicide risk factors. CONCLUSIONS: The findings confirm
      the importance of screening for substance use in early adolescence. The
      association between early substance use and suicide risk factors differed by
      gender; both research and intervention efforts need to incorporate gender
      differences.

PMID- 17210231
TI  - Hepatoprotection of Phyllanthus maderaspatensis against experimentally induced
      liver injury in rats.
AB  - The hexane extract of Phyllanthus maderaspatensis (200 and 100 mg/kg) showed
      significant hepatoprotection on carbon tetrachloride and thioacetamide induced
      liver damage in rats. The protective effect was evident from serum biochemical
      parameters and histopathological analysis. Rats treated with P. maderaspatensis
      remarkably prevented the elevation of serum AST, ALT and LDH and liver lipid
      peroxides in CCl(4) and thioacetamide treated rats. Hepatic glutathione levels
      significantly increased by the treatment with the extracts. Histopathological
      changes induced by CCl(4) and thioacetamide were also significantly reduced by
      the extract treatment. The activity of hexane extracts of P. maderaspatensis was
      comparable to that of silymarin, the reference hepatoprotective drug.

PMID- 17210232
TI  - Identification of cDNAs encoding viper venom hyaluronidases: cross-generic
      sequence conservation of full-length and unusually short variant transcripts.
AB  - The immobilisation of prey by snakes is most efficiently achieved by the rapid
      dissemination of venom from its site of injection into the blood stream.
      Hyaluronidase is a common component of snake venoms and has been termed the
      "venom spreading factor". In the absence of nucleotide or protein sequence data
      to confirm the functional identity of this venom component, we interrogated a
      venom gland EST database for the saw-scaled viper, Echis ocellatus (Nigeria),
      using the gene ontology (GO) term "carbohydrate metabolism". A single
      hyalurononglucosaminadase-activity matching sequence (EOC00242) was found and
      used to design PCR primers to acquire the full-length cDNA sequence. Although
      very different from the bee venom and mammalian hyaluronidase sequences, the E.
      ocellatus sequence retained all the catalytic, positional and structural residues
      that characterise this class of carbohydrate metabolising hydrolases. An
      extraordinarily high level of sequence identity (>95%) was observed in analogous
      venom gland cDNA sequences isolated (by PCR) from another saw-scaled viper
      species, E. pyramidum leakeyi (Kenya), and from the sahara horned viper, Cerastes
      cerastes cerastes (Egypt) and the puff adder, Bitis arietans (Nigeria). Smaller
      amplicons, lacking hyaluronidase catalytic residues because of 768 bp or 855 bp
      central deletions, appear to encode either truncated peptides without
      hyaluronidase activity, or are non-translated transcripts because they lack
      consensus translation initiating motifs.

PMID- 17210234
TI  - We are grateful to Professor Petruzzi on his remarks concerning our paper
      published recently in Maturitas (1).

PMID- 17210233
TI  - Birth and death of genes promoted by transposable elements in Oryza sativa.
AB  - Despite a wide distribution of transposable elements (TEs) in the genomes of
      higher eukaryotes, much of their evolutionary significance remains unclear.
      Recent studies have indicated that TEs are involved with biological processes
      such as gene regulation and the generation of new exons in mammals. In addition,
      the completion of the genome sequencings in Arabidopsis thaliana and Oryza sativa
      has permitted scientist to describe a genome-wide overview in plants. In this
      study, we examined the positions of TEs in the genome of O. sativa. Although we
      found that more than 10% of the structural genes contained TEs, they were
      underrepresented in exons compared with non-exonic regions. TEs also appeared to
      be inserted preferentially in 3'-untranslated regions in exons. These results
      suggested that purifying selection against TE insertion has played a major role
      during evolution. Moreover, our comparison of the numbers of TEs in the protein
      coding regions between single copy genes and duplicate genes showed that TEs were
      more frequent in duplicate than single copy genes. This observation indicated
      that gene duplication events created a large number of functionally redundant
      genes. Subsequently, many of them were destroyed by TEs because the redundant
      copies were released from purifying selection. Another biological role of TEs was
      found to be the recruitment of new exons. We found that approximately 2% of
      protein-coding genes contained TEs in their coding regions. Insertion of TEs in
      genic regions may have the potential to be an evolutionary driving force for the
      creation of new biological functions.

PMID- 17210235
TI  - Toxicological study on Glinus lotoides: a traditionally used taenicidal herb in
      Ethiopia.
AB  - Seeds of Glinus lotoides L. (Molluginaceae) are used traditionally in the
      treatment of tapeworm infestation in Ethiopia. Previous studies on its
      anthelmintic activities confirmed its traditional claims, but data on safety
      profile were lacking. To this effect, single and repeated dose oral toxicities of
      the methanolic extracts of seeds of Glinus lotoides were conducted in rats. Doses
      of 0, 1000 and 5000 mg/kg of crude extract of Glinus lotoides were employed in
      single dose toxicity studies, while doses of 0, 250, 500, and 1000 mg/kg were
      used in repeated toxicity studies. In the single dose toxicity test, oral
      administration of 5000 mg/kg of Glinus lotoides produced mortality in two females
      and one male on day 4. No significant differences in body and organ weights were
      observed between controls and treated surviving animals. Moreover, both gross and
      microscopic examinations of organs did not show detectable differences between
      controls and treated animals of both sexes. In repeated dose toxicity studies, no
      mortality was observed when varying doses of the extracts were administered per
      day for a period of 28 days. There were no significant differences in body
      weight, absolute and relative organ weights between controls and treated animals
      of both sexes. Hematological analysis showed no differences in most parameters
      examined. In the biochemistry parameter analysis, no significant change occurred.
      Pathologically, neither gross abnormalities nor histopathological changes were
      observed. These finding suggest that none of the organs appeared to be target and
      the data could provide satisfactory preclinical evidence of safety to launch
      clinical trial on standardized formulation of plant extracts.

PMID- 17210237
TI  - Canine scavenging of human remains in an indoor setting.
AB  - This case study documents the nearly complete consumption of adult human remains
      by two domestic dogs (Canis familiaris) inside a residence. While scavenging
      behavior has been observed for coyotes, wolves, hyenas and other canines in
      natural outdoor environments, little information is available concerning canine
      scavenging of human remains in an indoor setting. In this case, the dogs were
      confined with the body inside a residence for approximately 1 month. The impact
      of intrinsic and extrinsic factors on canine scavenging behavior and the
      postmortem interval are examined, such as clothing on the body, perimortem
      trauma, drug ingestion and the availability of alternative food sources. While
      cases of canine scavenging of their owners are scant in the literature, this
      phenomenon is probably not uncommon, particularly among the elderly and indigent
      who live alone with pets and are socially isolated.

PMID- 17210236
TI  - Activity of essential oils from Brazilian medicinal plants on Escherichia coli.
AB  - Essential oils obtained from leaves of 29 medicinal plants commonly used in
      Brazil were screened against 13 different Escherichia coli serotypes. The oils
      were obtained by water-distillation using a Clevenger-type system and their
      minimal inhibitory concentration (MIC) were determined by microdilution method.
      Essential oil from Cymbopogon martinii exhibited a broad inhibition spectrum,
      presenting strong activity (MIC between 100 and 500 microg/mL) against 10 out of
      13 Escherichia coli serotypes: three enterotoxigenic, two enteropathogenic, three
      enteroinvasive and two shiga-toxin producers. C. winterianus inhibited strongly
      two enterotoxigenic, one enteropathogenic, one enteroinvasive and one shiga-toxin
      producer serotypes. Aloysia triphylla also shows good potential to kill
      Escherichia coli with moderate to strong inhibition. Other essential oils showed
      antimicrobial properties, however with a more restricted action against the
      serotypes studied. Chemical analysis of Cymbopogon martinii essential oil
      performed by gas chromatography (GC) and gas chromatography/mass spectrometry (GC
      MS) showed the presence of compounds with known antimicrobial activity, including
      geraniol, geranyl acetate and trans-cariophyllene, which tested separately,
      indicated geraniol as antimicrobial active compound. The significant
      antibacterial activity of Cymbopogon martinii oil suggests that they could serve
      as a source for compounds with therapeutic potential.

PMID- 17210238
TI  - Estimating the uncertainty associated with Widmark's equation as commonly applied
      in forensic toxicology.
AB  - No computation is performed more frequently by forensic toxicologists than that
      involving Widmark's equation. The equation is employed to estimate either the
      number of drinks consumed or the corresponding blood or breath alcohol
      concentration. Despite the wide use of Widmark's equation, rarely is an
      uncertainty estimate also provided. Estimates from Widmark's equation involve at
      least seven uncertain random variables. Uncertainty estimates are presented that
      rely on methods of general error propagation compared to a method developed by
      Widmark. Assuming reasonable variable and uncertainty estimates, the error
      propagation method yielded for N=10.4 drinks, a combined uncertainty (standard
      deviation) of 1.3 drinks (CV=12.3%). Similarly, estimating the blood alcohol
      concentration yielded for 0.120 g/100 ml, an uncertainty of 0.0255 g/100 ml
      (CV=21.2%). Widmark's uncertainty method yielded 1.6 drinks (CV=15.4%). The
      derivation of Widmark's uncertainty estimate is also presented, showing that he
      considered only rho and beta to be uncertain. Widmark estimates for the number of
      drinks should include a 2CV estimate of approximately 25% while the blood alcohol
      concentration estimate should include a 2CV estimate of approximately 42%.
      Including valid estimates of uncertainty should enhance the legal admissibility
      and confidence for Widmark estimations.

PMID- 17210239
TI  - Effects of plasma progesterone concentrations on LH release and ovulation in beef
      cattle given GnRH.
AB  - The effects of plasma progesterone concentrations on LH release and ovulation in
      beef cattle given 100 microg of GnRH im were determined in three experiments. In
      Experiment 1, heifers were given GnRH 3, 6 or 9 days after ovulation; 8/9, 5/9
      and 2/9 ovulated (P<0.02). Mean plasma concentrations of progesterone were lowest
      (P<0.01) and of LH were highest (P<0.03) in heifers treated 3 days after
      ovulation. In Experiment 2, heifers received no treatment (Control) or one or two
      previously used CIDR inserts (Low-P4 and High-P4 groups, respectively) on Day 4
      (estrus=Day 0). On Day 5, the Low-P4 group received prostaglandin F(2alpha) (PGF)
      twice, 12 h apart and on Day 6, all heifers received GnRH. Compared to heifers in
      the Control and Low-P4 groups, heifers in the High-P4 group had higher (P<0.01)
      plasma progesterone concentrations on Day 6 (3.0+/-0.3, 3.0+/-0.3 and 5.7+/-0.4
      ng/ml, respectively; mean+/-S.E.M.) and a lower (P<0.01) incidence of GnRH
      induced ovulation (10/10, 9/10 and 3/10). In Experiment 3, 4-6 days after
      ovulation, 20 beef heifers and 20 suckled beef cows were given a once-used CIDR,
      the two largest follicles were ablated, and the cattle were allocated to receive
      either PGF (repeated 12h later) or no additional treatment (Low-P4 and High-P4,
      respectively). All cattle received GnRH 6-8 days after follicular ablation. There
      was no difference between heifers and cows for ovulatory response (77.7 and
      78.9%, P<0.9) or the GnRH-induced LH surge (P<0.3). However, the Low-P4 group had
      a higher (P<0.01) ovulatory response (94.7% versus 61.1%) and a greater LH surge
      of longer duration (P<0.001). In conclusion, although high plasma progesterone
      concentrations reduced both GnRH-induced increases in plasma LH concentrations
      and ovulatory responses in beef cattle, the hypothesis that heifers were more
      sensitive than cows to the suppressive effects of progesterone was not supported.

PMID- 17210240
TI  - Evaluation of the Tokuhashi prognosis score and its modifications in 217 patients
      with vertebral metastases.
AB  - AIM: The Tokuhashi prognosis score consists of six parameters. The sum of points
      rated for each parameter can be correlated with the prognosis. This study
      evaluates the score variations that have been done by different authors and
      Tokuhashi et al. themselves. METHODS: Two hundred and seventeen consecutive
      patients, surgically treated for vertebral metastases, were studied
      retrospectively. We calculated the original and modified score of Tokuhashi and
      evaluated the predictive value for the individual life expectancy. RESULTS: The
      original and modified Tokuhashi score assured a significant predictive value.
      Modified criteria by the authors showed the highest reliability between the
      predicted and real survival, and the patients could be allocated correctly to the
      desirable instrumentation. CONCLUSION: The original and modified Tokuhashi score
      showed a significant predictive value. The modified criteria by the authors
      showed the highest reliability between predicted and real survival.

PMID- 17210241
TI  - Porcine kallikrein gene family: genomic structure, mapping, and differential
      expression analysis.
AB  - Kallikreins belong to a family of serine proteases that are widespread throughout
      living organisms, expressed in diverse tissue-specific patterns, and known to
      have highly diverse physiological functions. The 15 human and 24 mouse
      kallikreins have been implicated in pathophysiology of brain, kidney, and
      respiratory and reproductive systems and often are used as cancer biomarkers. To
      better elucidate the structure and evolutionary origin of this important gene
      family in the pig, we have constructed a contiguous BAC clone-derived physical
      map of the porcine kallikrein gene region and have fully sequenced a BAC clone
      containing 13 kallikrein genes, 11 of which are novel. Radiation hybrid mapping
      assigns this kallikrein-gene-rich region to porcine chromosome 6. Phylogenetic
      and percent identity plot-based analyses revealed strong structure and order
      conservation of kallikreins among four mammalian species. Reverse transcriptase
      polymerase chain reaction-based expression analysis of porcine kallikreins showed
      a complex expression pattern across different tissues with the thymus being the
      only tissue expressing all 13 kallikrein genes. [The sequence data described in
      this paper has been submitted to GenBank under Accession No. AC149292].

PMID- 17210243
TI  - The role of cognition and adaptive behavior in employment of people with mental
      retardation.
AB  - Few studies have specifically investigated the cognitive correlates of employment
      for persons with mental retardation. To evaluate the relationship of cognitive
      and adaptive functioning to work status, 56 competitively employed and 55
      unemployed individuals with mental retardation underwent a comprehensive
      neuropsychological and adaptive behavioral evaluation. Results of multivariate
      analysis of covariance (MANCOVA) revealed significant group differences in
      cognitive and adaptive behavioral domains controlling for gender and severity of
      mental retardation. Follow-up ANCOVAs showed that the employed group performed
      significantly better than the unemployed group on measures of attention, memory,
      verbal comprehension, visual perception, and adaptive behavior. Using
      discriminant function analysis, 73.2 percent of the employed and 76.4 percent of
      the unemployed people were predicted correctly. These results suggest that
      adaptive behavior and specific aspects of cognitive functioning are significant
      predictors of successful employment for persons with mental retardation.

PMID- 17210242
TI  - Distribution and cellular localization of imidazoleacetic acid-ribotide, an
      endogenous ligand at imidazol(in)e and adrenergic receptors, in rat brain.
AB  - Imidazoleacetic acid-ribotide (IAA-RP) is a putative neurotransmitter/modulator
      recently discovered in mammalian brain. The present study examines the
      distribution of IAA-RP in the rat CNS using a highly specific antiserum raised in
      rabbit against IAA-RP with immunostaining of aldehyde-fixed rat CNS. IAA-RP
      immunoreactive neurons were present throughout the neuraxis; neuroglia were not
      labeled. In each region, only a subset of the neuronal pool was immunostained. In
      the forebrain, ribotide-immunolabeled neurons were common in neocortex, in
      hippocampal formation, and in subcortical structures including basal ganglia,
      thalamus and hypothalamus. Labeling was prominent in limbic areas including
      olfactory bulb, basal forebrain, pyriform cortex and amygdala. In the mid- and
      hindbrain, immunolabeled neurons were concentrated in specific nuclei and, in
      some areas, in specific subregions of those nuclei. Structures of the motor
      system, including cranial nerve motor nuclei, precerebellar nuclei, the
      substantia nigra, and the red nucleus were clearly labeled. Staining was intense
      in cells and/or puncta in the rostral and caudal ventrolateral medullary
      reticular formation, nucleus tractus solitarius and the caudal vestibular nuclear
      complex. Within neurons, the ribotide was found predominantly in somata and
      dendrites; some myelinated axons and occasional synaptic terminals were also
      immunostained. These data indicate that IAA-RP contributes to the neurochemical
      phenotype of many neuronal populations and further supports our suggestion that,
      in autonomic structures, IAA-RP may serve as a chemical mediator in complex
      circuits involved in blood pressure regulation and, more generally, sympathetic
      drive.

PMID- 17210244
TI  - Fine specificity mapping of autoantigens targeted by anti-centromere
      autoantibodies.
AB  - Autoantibodies to centromeric proteins are commonly found in sera of limited
      scleroderma and other rheumatic disease patients. To better understand the
      inciting events and possible pathogenic mechanisms of these autoimmune responses,
      this study identified the common antigenic targets of CENP-A in scleroderma
      patient sera. Utilizing samples from 263 anti-centromere immunofluorescence
      positive patients, 93.5% were found to have anti-CENP-A reactivity and 95.4% had
      anti-CENP-B reactivity by ELISA. Very few patient samples exclusively targeted
      CENP-A (2.7%) or CENP-B (4.2%). Select patient sera were tested for reactivity
      with solid phase overlapping decapeptides of CENP-A. Four distinct epitopes of
      CENP-A were identified. Epitopes 2 and 3 were confirmed by additional testing of
      263 patient sera by ELISA for reactivity with these sequences constructed as
      multiple antigenic peptides. Inhibition CENP-A Western blots also confirmed the
      specificity of these humoral peptide immune responses in a subset of patient
      sera. The first three arginine residues (aa 4-6) of CENP-A appear essential for
      antibody recognition, as replacing these arginines with glycine residues reduced
      antibody binding to the expressed CENP-A protein by an average of 93.2% (range 80
      100%). In selected patients with serial samples spanning nearly a decade, humoral
      epitope binding patterns were quite stable and showed no epitope spreading over
      time. This epitope mapping study identifies key antigenic targets of the anti
      centromere response and establishes that the majority of the responses depend on
      key amino-terminal residues.

PMID- 17210245
TI  - ZO-1 is required for protein kinase C gamma-driven disassembly of connexin 43.
AB  - We have previously reported that protein kinase C gamma (PKC-gamma) is activated
      by phorbol-12-myristate-13-acetate (TPA) and that this causes PKC-gamma
      translocation to membranes and phosphorylation of the gap junction protein,
      connexin 43 (Cx43). This phosphorylation, on S368 of Cx43, causes disassembly of
      Cx43 out of cell junctional plaques resulting in the inhibition of dye transfer.
      The purpose of this study is to identify the specific role of zonula occludens
      protein-1 (ZO-1), a tight junction protein with recently established effects on
      gap junctions, in this PKC-gamma-driven Cx43 disassembly. For this purpose, ZO-1
      levels in lens epithelial cells in culture were decreased by up to 70% using
      specific siRNA. The down-regulation of ZO-1 caused a stable interaction of PKC
      gamma with Cx43 even without normal enzyme activation by TPA. However, after TPA
      activation of the PKC-gamma, the Cx43 did not disassemble out of plaques even
      though the PKC-gamma enzyme was activated and the Cx43 was phosphorylated on
      S368. Confocal microscopy demonstrated that the siRNA treatment caused a loss of
      ZO-1 from borders of large junctional Cx43 cell-to-cell plaques and resulted in
      the accumulation of Cx43 aggregates inside of cells. Loss of the specific
      "plaquetosome" arrangement of large Cx43 plaques surrounded by ZO-1 was
      accompanied by a complete loss of functional dye transfer. These results suggest
      that ZO-1 is required for Cx43 control, both for dye transfer, and, for the PKC
      gamma-driven disassembly response.

PMID- 17210247
TI  - Spin relaxation and ultra-slow Li motion in an aluminosilicate glass ceramic.
AB  - The ion dynamics in a lithium aluminosilicate glass ceramic was studied using
      stimulated-echo 7Li-NMR. For temperatures 300 K<T<450 K the hopping correlation
      times, tau(C), were determined from the decay of the quadrupolar spin-alignment
      amplitude. The decay times were thermally activated with an energy barrier of
      0.61 eV, in agreement with conductivity measurements. For T<300 K the temperature
      dependence of the decay times, now corresponding to T1Q, was much weaker. The T1Q
      times followed the same trend as the independently measured spin-lattice
      relaxation times, T1, but were a factor of about three shorter than those. The
      theoretical ratio of T1/T1Q is shown to be 25/8 in the slow-motion regime if
      quadrupolar spin relaxation prevails. This result explains the present
      observation and similar ones made for several Li ion conductors. The relaxation
      of the octupolar spin-alignment order is discussed.

PMID- 17210248
TI  - Transcription factors in hematopoietic malignancies.
AB  - Transcription factors comprise a high proportion of the proteins with
      dysregulated expression or altered activity in cancer cells. In recent years,
      great progress has been made in elucidating crucial pathways in leukemogenesis,
      partially by identifying key transcription factors that are normally
      indispensable for hematopoiesis but which are often associated with malignant
      transformation when functioning improperly. The significance of transcription
      factors is highlighted by the multiple mechanisms used by leukemic cells to
      abrogate their normal activity. Delineating these mechanisms can benefit the
      diagnosis and treatment of hematological malignancies and might also be
      applicable to certain solid tumors.

PMID- 17210246
TI  - Activated Ras induces cytoplasmic vacuolation and non-apoptotic death in
      glioblastoma cells via novel effector pathways.
AB  - Expression of activated H-Ras induces a unique form of non-apoptotic cell death
      in human glioblastoma cells and other specific tumor cell lines. The major
      cytopathological features of this form of death are the accumulation of large
      phase-lucent, LAMP1-positive, cytoplasmic vacuoles. In this study we sought to
      determine if induction of cytoplasmic vacuolation a) depends on Ras
      farnesylation, b) is specific to H-Ras, and c) is mediated by signaling through
      the major known Ras effector pathways. We find that the unusual effects of
      activated H-Ras depend on farnesylation and membrane association of the GTPase.
      Both H-Ras(G12V) and K-Ras4B(G12V) stimulate vacuolation, but activated forms of
      Cdc42 and RhoA do not. Amino acid substitutions in the Ras effector domain, which
      are known to selectively impair its interactions with Raf kinase, class-I
      phosphatidylinositide 3-kinase (PI3K), or Ral nucleotide exchange factors,
      initially pointed to Raf as a possible mediator of cell vacuolation. However, the
      MEK inhibitor, PD98059, did not block the induction of vacuoles, and
      constitutively active Raf-Caax did not mimic the effects of Ras(G12V).
      Introduction of normal PTEN together with H-Ras(G12V) into U251 glioblastoma
      cells reduced the PI3K-dependent activation of Akt, but had no effect on
      vacuolation. Finally, co-expression of H-Ras(G12V) with a dominant-negative form
      of RalA did not suppress vacuolation. Taken together, the observations indicate
      that Ras activates non-conventional and perhaps unique effector pathways to
      induce cytoplasmic vacuolation in glioblastoma cells. Identification of the
      relevant signaling pathways may uncover specific molecular targets that can be
      manipulated to activate non-apoptotic cell death in this type of cancer.

PMID- 17210249
TI  - 1alpha,25-Dihydroxyvitamin D3 enhances proliferation of rat prostate cancer cells
      in the presence of living bone.
AB  - 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) is known to inhibit
      prostate cancer cells in vitro. Its effects on proliferation in the presence of
      living bone have not been reported, but are especially relevant since much of the
      morbidity and mortality associated with prostate cancer is due to metastatic bone
      disease. We investigated the effect of 1alpha,25(OH)(2)D(3) on MatLyLu-beta(2)
      cells (MatLyLu cells), a rat prostate cancer line, co-cultured in transwells with
      living rat calvaria. Cultures of MatLyLu cells with living calvaria treated with
      1alpha,25(OH)(2)D(3) exhibited a statistically significant increase in
      proliferation (range 1.4 to 1.7-fold; p<0.05). Cultures of MatLylu cells alone,
      with spleen cells, muscle tissue, or with living or inactivated calvarial bone
      showed no differences in proliferation. To investigate the mechanism for enhanced
      proliferation, Galardin, a matrix metalloproteinase (MMP) inhibitor, or
      pamidronate, an antiresorptive agent, was added. Enhanced proliferation was
      prevented by either agent, but not to an equal extent. The presence of
      1alpha,25(OH)(2)D(3) may lead to proteolytic release or activation of growth
      factors from bone. These results may explain the variability in reports on the in
      vivo effects of Vitamin D and suggest a potential concern in using Vitamin D or
      its analogs alone in patients with metastatic prostate cancer.

PMID- 17210250
TI  - Challenges in the development of mGluR5 positive allosteric modulators: the
      discovery of CPPHA.
AB  - This Letter describes, for the first time, the synthesis and SAR, developed
      through an iterative analog library approach, that led to the discovery of the
      positive allosteric modulator (PAM) of the metabotropic glutamate receptor mGluR5
      CPPHA. Binding to a unique allosteric binding site distinct from other mGluR5
      PAMs, CPPHA has been the focus of numerous pharmacology studies by several
      laboratories.

PMID- 17210251
TI  - Synthesis and evaluation of aryl thioxothiazolidinone inhibitors of ADAMTS-5
      (Aggrecanase-2).
AB  - 5-Benzylidene-2-thioxo-thiazolidin-4-one inhibitors of ADAMTS-5 (Aggrecanase-2)
      have been prepared via commercially available starting materials. The identified
      compounds show micromolar ADAMTS-5 potency and demonstrate SAR trends for both
      the aryl group and thioxothiazolidinone zinc chelator. This series of compounds
      represents steps toward a metalloprotease inhibitor as a disease-modifying
      osteoarthritis drug.

PMID- 17210252
TI  - 5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5.
AB  - A series of 5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors
      of ADAMTS-5 (aggrecanase-2) is described. These compounds show microM functional
      inhibition of ADAMTS-5, and represent a new class of agents with the potential of
      inhibiting degradation of aggrecan, a major component of cartilage which is lost
      in osteoporosis. Compound 12 is noteworthy in that it has an ADAMTS-5 IC50: 1.1
      microM and shows >40-fold functional selectivity over ADAMTS-4 (aggrecanase-1).

PMID- 17210253
TI  - Sticky fingers: zinc-fingers as protein-recognition motifs.
AB  - Zinc-fingers (ZnFs) are extremely abundant in higher eukaryotes. Once considered
      to function exclusively as sequence-specific DNA-binding motifs, ZnFs are now
      known to have additional activities such as the recognition of RNA and other
      proteins. Here we discuss recent advances in our understanding of ZnFs as
      specific modules for protein recognition. Structural studies of ZnF complexes
      reveal considerable diversity in terms of protein partners, binding modes and
      affinities, and highlight the often underestimated versatility of ZnF structure
      and function. An appreciation of the structural features of ZnF-protein
      interactions will contribute to our ability to engineer and to use ZnFs with
      tailored protein-binding properties.

PMID- 17210254
TI  - Design and synthesis of pyrimido[4,5-b][1,4]benzothiazine derivatives, as potent
      15-lipoxygenase inhibitors.
AB  - A group of 2-substituted pyrimido[4,5-b][1,4]benzothiazines were designed,
      synthesized, and evaluated as potential inhibitors of 15-lipoxygenase (15-LO).
      Compounds 4d and 4e showed the best IC50 of 15-LO inhibition (IC50=18 and 34
      microM, respectively). All compounds were docked into 15-LO. As a result the
      sulfur atom was oriented toward the iron atom of the active site of 15-LO. We
      suggest the interaction of the iron atom is essential for the activity of the
      inhibitors.

PMID- 17210255
TI  - Inhibition of FLT3 and PDGFR tyrosine kinase activity by bis(benzo[b]furan-2
      yl)methanones.
AB  - A series of bis(benzo[b]furan-2-yl)methanones was synthesized and tested for
      inhibition of FLT3 and PDGFR autophosphorylation. Mostly, C-5 substitution leads
      to PDGFR selectivity, which was strongest in the case of the 5,5'-dimethoxy
      derivative. The 5,5'-diamino and the 6,6'-dihydroxy compounds are more active at
      FLT3. At both kinases, the potency of the best inhibitors approaches IC50 values
      of ca. 0.5 microM. Molecular modeling studies suggest that the
      bisbenzofuranylmethanones are able to fit into the same binding site as their
      indolyl analogues which have been suggested to form a bidentate hydrogen bridge
      with the backbone in the hinge regions. The loss of one H bond by the NH-O
      exchange might be partially compensated by, for example, the weak interaction of
      one furanyl oxygen with FLT3 Cys-828.

PMID- 17210256
TI  - In vivo h-VEGF165 gene transfer improves early endothelialisation and patency in
      synthetic vascular grafts.
AB  - OBJECTIVES: Small-diameter synthetic vascular graft performance is inferior to
      autologous vein grafts. This study tested the hypotheses that local in vivo
      administration of plasmids encoding for human vascular endothelial growth factor
      (VEGF), or co-administration of plasmids encoding for human vascular endothelial
      growth factor/plasmids encoding for fibroblast growth factor-2 in the tissues
      surrounding a porous synthetic vascular graft would enhance graft
      endothelialisation and, consecutively, graft patency. METHODS: First, optimal
      gene for small-diameter synthetic graft endothelialisation was studied in rat
      abdominal aorta model (n=132): plasmids encoding for human vascular endothelial
      growth factor; co-administration of plasmids encoding for human vascular
      endothelial growth factor/plasmids encoding for fibroblast growth factor-2; or
      control plasmids were injected around 60 microm ePTFE graft. Second, optimal
      small-diameter synthetic graft design for endothelialisation was explored in
      rabbit abdominal aorta model (n=90). Various ePTFE grafts or pre-clotted
      polyester grafts were used with/without plasmids encoding for human vascular
      endothelial growth factor. Third, clinically used medium-size synthetic grafts
      were investigated with/without plasmids encoding for human vascular endothelial
      growth factor in dog carotid (n=20) and femoral arteries (n=15).
      Endothelialisation was assessed in midgraft area with scanning electron
      microscopy. RESULTS: In rats, plasmids encoding for human vascular endothelial
      growth factor enhanced endothelialisation; whereas co-administration of plasmids
      encoding for human vascular endothelial growth factor/plasmids encoding for
      fibroblast growth factor-2 had worst outcome at 1 week (NS), 2 weeks (P=0.01) and
      4 weeks (P=0.02). In rabbits, pre-clotted polyester grafts had a trend for faster
      endothelialisation than ePTFE grafts (P=0.08); whereas plasmids encoding for
      human vascular endothelial growth factor enhanced endothelialisation compared to
      controls at 2 weeks (P=0.06), however, the effect reversed at 4 weeks (P=0.03).
      In dogs, synthetic graft patency was improved by plasmids encoding for human
      vascular endothelial growth factor in femoral position (P=0.103); whereas all
      carotid grafts were patent at 6 weeks. CONCLUSIONS: Thus, these data suggested
      that endothelialisation was fastest in pre-clotted polyester grafts; and that
      local application of plasmids encoding for human vascular endothelial growth
      factor had a potential to improve early endothelialisation and patency in
      synthetic vascular grafts.

PMID- 17210257
TI  - Zebrafish as a powerful vertebrate model system for in vivo studies of cell
      death.
AB  - Understanding and manipulating cell death pathways are critical to our ability to
      treat human degenerative diseases and cancer. The zebrafish Danio rerio, a common
      aquatic pet, has evolved as a powerful tool for the discovery of genes regulating
      cellular suicide both during normal vertebrate development and after genetic or
      environmental insult. In this review, we describe the techniques that can be
      applied to studying cell death in zebrafish as well as highlighting what has been
      discovered so far. Finally, we discuss future perspectives in the field and how
      they relate to human disease.

PMID- 17210258
TI  - Identification of differentially expressed genes in lipopolysaccharide-stimulated
      yellow grouper Epinephelus awoara spleen.
AB  - A subtracted cDNA library from lipopolysaccharide (LPS)-stimulated Epinephelus
      awoara spleen was constructed using the suppression subtractive hybridization
      (SSH). Random clones (209) were selected and sequenced. After assembling, 36
      contigs and 56 singlets (accession numbers: EB410743-EB410834) were finally
      obtained, some of which were immune-related genes. A reverse transcription
      polymerase chain reaction (RT-PCR) analysis of the expression patterns of eight
      transcripts showed that seven of them were up-regulated after 24 h of LPS
      stimulation. Furthermore, full-length cDNAs of homologues of defender against
      cell death 1 (DAD1) and allograft inflammatory factor-1 (AIF-1) were obtained by
      RACE-PCR.

PMID- 17210259
TI  - Dopamine depresses immunity in the tiger shrimp Penaeus monodon.
AB  - The total haemocyte count (THC), differential haemocyte count (DHC),
      phenoloxidase activity, respiratory bursts (release of superoxide anion),
      superoxide dismutase activity, phagocytic activity and clearance efficiency to
      the pathogen Photobacterium damsela were measured when tiger shrimp Penaeus
      monodon (13.5+/-1.5 g) were individually injected with saline or dopamine at 10(
      8), 10(-7), or 10(-6)mol shrimp(-1). Results showed that a transient period of
      immunosuppression occurred between 2 and 8h after injection of dopamine for all
      immune parameters except circulating haemocytes, and all immune parameters had
      returned to control values within 8-16 h after receiving dopamine. The injection
      of dopamine also significantly increased the mortality of P. monodon challenged
      with the pathogen Pho. damsela. These results suggest that stress-inducing
      dopamine suppresses the immune system, which in turn promotes the susceptibility
      of P. monodon to Pho. damsela.

PMID- 17210260
TI  - The partial mitochondrial genome of the Cephalothrix rufifrons (Nemertea,
      Palaeonemertea): characterization and implications for the phylogenetic position
      of Nemertea.
AB  - A continuous 10.1kb fragment of the Cephalothrix rufifrons (Nemertea,
      Palaeonemertea) mitochondrial genome was sequenced and characterized to further
      assess organization of protostome mitochondrial genomes and evaluate the
      phylogenetic potential of gene arrangement and amino acid characters. The genome
      is A-T rich (72%), and this biased base composition is partly reflected in codon
      usage. Inferred tRNA secondary structures are typical of those reported for other
      metazoan mitochondrial DNAs. The arrangement of the 26 genes contained in the
      fragment exhibits marked similarity to those of many protostome taxa, most
      notably molluscs with highly conserved arrangements and a phoronid. Separate and
      simultaneous phylogenetic analyses of inferred amino acid sequences and gene
      adjacencies place the nemertean within the protostomes among coelomate
      lophotrochozoan taxa, but do not find a well-supported sister taxon link.

PMID- 17210261
TI  - Valproate, weight gain and carbohydrate craving: a gender study.
AB  - PURPOSE: To compare the incidence and magnitude of weight gain associated with
      valproic acid (VPA) monotherapy in male and female epilepsy patients and to
      determine possible gender-specific differences in frequency of carbohydrate
      craving, body-composition, glucose homeostasis and lipid metabolism. METHODS:
      Epilepsy patients on VPA monotherapy were consecutively recruited at the
      outpatient clinic of the Department of Neurology, Innsbruck Medical University.
      Weight gain during VPA-therapy, frequency of carbohydrate craving and physical
      exercise, sociopsychological problems and family history for diabetes were
      obtained from all patients. Clinical data also comprised body-impedance analysis,
      body mass index and waist-to-hip ratio. Morning fasting blood samples were drawn
      to determine serum leptin, glucose and lipid concentrations, as well as insulin,
      C-reactive protein and TNF-alpha. RESULTS: One hundred and six patients (55
      women) were enrolled in the study. Significant weight gain was seen during VPA
      therapy in both genders (each p<0.001) with women experiencing increment of
      weight more frequently and more pronounced than did men. Analyses of patients who
      gained weight during VPA-therapy revealed significantly higher serum leptin
      concentrations in women than in men (p<0.001). Women also revealed significantly
      higher high-density lipoprotein-cholesterol and lower triglyceride concentrations
      than men (p=0.004 and 0.014, respectively). Frequency of carbohydrate craving was
      25.8% in women and 14.3% in men. More women tried to lose or control weight
      through diet than did men (22.6% versus 7.1%). Moreover, weight gain as a
      sociopsychological problem was more numorous in women than in men. CONCLUSION:
      Women are more prone to gain weight during VPA therapy though higher frequency of
      diet and sociopsychological burden than men, which might possibly be related to
      leptin-resitance and a higher frequency of carbohydrate craving.

PMID- 17210262
TI  - Serum-free mouse embryo cells generate a self-sustaining feedback loop for an
      astrocyte marker protein and respond to cytokines and bisphenol A in accordance
      with the subtle difference in their differentiation state.
AB  - Serum-free mouse embryo (SFME) cells, the astrocyte progenitor cells in the
      central nervous system, generated a self-sustaining feedback loop for glial
      fibrillary acidic protein (GFAP) expression after a period of cell passages. The
      period required was about 150 days (30 passages). SFME and high-GFAP-expressing
      SFME (G-SFME) cells were exposed to 10 ng/ml leukemia inhibitory factor (LIF) and
      10 ng/ml bone morphogenetic protein 2 (BMP2) to induce differentiation and their
      responses to cytokine signals were analyzed. Although differentiation was
      significantly induced in both cell types, SFME cells showed more obvious
      responses to the cytokine signals. Various concentrations of bisphenol A (BPA)
      (0.1 pg/ml to 1 microg/ml) were added to determine its effects on cell
      differentiation. A completely serum-free culture was developed for effective
      differentiation of G-SFME cells with LIF and BMP2, and GFAP expression was
      significantly increased in the presence of 1-100 pg/ml BPA. These increases were
      attributed to excessive activation of signal transducer and activator of
      transcription 3 (STAT3) and mothers against decapentaplegic homolog 1 (Smad1) by
      the low-level BPA. The data obtained in the present study revealed that the
      sensitivity of the cells to LIF, BMP2 and BPA could change upon cell
      differentiation, suggesting that the cells may possibly respond differently to
      cytokines and endocrine disruptors depending on subtle differences in their
      differentiation state.

PMID- 17210263
TI  - A role for Wnt/planar cell polarity signaling during lens fiber cell
      differentiation?
AB  - Wnt signaling through frizzled (Fz) receptors plays key roles in just about every
      developmental system that has been studied. Several Wnt-Fz signaling pathways
      have been identified including the Wnt/planar cell polarity (PCP) pathway. PCP
      signaling is crucial for many developmental processes that require major
      cytoskeletal rearrangements. Downstream of Fz, PCP signaling is thought to
      involve the GTPases, Rho, Rac and Cdc42 and regulation of the JNK cascade. Here
      we report on the localization of these GTPases and JNK in the lens and assess
      their involvement in the cytoskeletal reorganisation that is a key element of FGF
      induced lens fiber cell differentiation.

PMID- 17210264
TI  - Regulation of Drosophila TRPC channels by protein and lipid interactions.
AB  - The Drosophila TRPC channels TRP and TRPL are the founding members of the TRP
      superfamily of ion channels, proteins likely to be important components of
      calcium influx pathways. The activation of these channels in the context of fly
      phototransduction is one of the few in vivo models for TRPC channel activation
      and has served as a paradigm for understanding TRPC function. TRP and TRPL are
      activated by G-protein coupled PI(4,5)P(2) hydrolysis through a mechanism in
      which IP(3) receptor mediated calcium release seems dispensable. Recent analysis
      has provided compelling evidence that the accurate turnover of PI(4,5)P(2)
      generated lipid messengers in essential for regulating TRP and TRPL activity. TRP
      channels also appear to exist in the context of a macromolecular complex
      containing key components involved in activation such as phospholipase Cbeta and
      protein kinase C. This complex may be important for activation. The role of these
      protein and lipid elements in regulating TRP and TRPL activity is discussed in
      this review.

PMID- 17210265
TI  - Deletions in mRNA encoding the chicken leptin receptor gene binding domain.
AB  - The leptin binding domain of the chicken leptin receptor gene was analyzed for
      alternative splicing. Polymerase chain reaction (PCR) primers were designed to
      amplify exons 8-14 of the gene which is known to encode the leptin binding
      domain. Four cDNA products from reverse transcribed chicken anterior pituitary
      and basal hypothalamic RNA were generated. One encoded the predicted full length
      leptin binding domain while the other cDNAs were shorter as a consequence of
      different deletions in exon 9, and one had a further deletion in exon 10. Two of
      the deletions in exon 9 had the potential to disrupt the leptin binding domain.
      Genomic DNA analysis demonstrated that the alternative splicing sites with
      potential to generate these deletions occurred in the chicken genome. All four
      cDNAs were amplified from reverse transcribed RNA from basal hypothalami and
      anterior pituitary glands from four breeds of chicken, demonstrating that the
      nucleotide deletions were not breed specific. In conclusion, alternative spliced
      forms of the leptin binding domain in chicken leptin receptor mRNAs occur in the
      chicken neuroendocrine system with the potential to give rise to alternative
      transcripts which could modulate the biological action of the ligand for the
      chicken leptin receptor.

PMID- 17210266
TI  - Inter-examiner reliability of four static palpation tests used for assessing
      pelvic dysfunction.
AB  - In muscle energy technique (MET), palpation is an important tool aimed at
      detecting asymmetry and selecting interventions. The aim of this study was to
      test the inter-examiner reliability of static palpation of the transverse
      processes of L5 (L5), sacral sulci (SS), inferior lateral angles of the sacrum
      (ILA), and the medial malleoli (MM) in a clinical setting. Twenty-five
      participants, aged 18-78 years, with low back pain and/or sacroiliac pain with or
      without radiating pain to the knee, were independently examined by two
      experienced physiotherapists. For L5, SS, ILA, the proportion of observed
      agreement was 40-44% and the kappa coefficient 0.11 (SE=0.12) to 0.17 (SE=0.10).
      For MM, the observed agreement was 52% and the kappa coefficient 0.28 (SE=0.15).
      Differences in palpation technique seem to be the most likely source of the low
      inter-examiner reliability in this study. For clinical practise, continued use of
      these tests as methods for detecting asymmetry and selecting interventions is of
      doubtful utility.

PMID- 17210267
TI  - Discordant outcome of perinatal transmission of hepatitis C in twin pregnancies.
AB  - BACKGROUND: Mother to infant transmission of hepatitis C virus (HCV) is dependent
      on significant HCV viraemia being present in the mother. As yet there are no
      appropriate interventions to prevent perinatal transmission. The investigation of
      twin pregnancies where only one twin is infected may reveal further information
      relating to transmission and specific risks. Evaluation of these risks could
      affect decisions about the management of the deliveries of these mothers while
      more appropriate interventions are evaluated. STUDY DESIGN: The laboratory
      database was searched for all twins referred for testing at the Children's
      Hospital Liver Unit. The mothers and health care providers were contacted to gain
      more information about the pregnancies and deliveries of all of the twins.
      RESULTS: Four sets of twins had been investigated for HCV. In all cases only one
      twin had been infected. In three out of four cases the second twin had become
      infected. All of the twins were girls and the larger twin in each pair became
      infected. Premature rupture of membranes was associated with transmission in the
      only case in which the first-born became infected. There was no invasive foetal
      monitoring or episiotomy in any of the deliveries SUMMARY AND CONCLUSIONS:
      Transmission of HCV is more likely to affect the second twin, perhaps because
      placental separation during the delivery of the second twin exposes the infant to
      infection. Until effective interventions such as vaccination of newborns or
      antiviral treatment of mothers are evaluated, elective caesarean section could be
      recommended for HCV twin pregnancies in order to avoid premature membrane rupture
      and infection of the second twin.

PMID- 17210268
TI  - A new hepatitis B virus vaccine escape mutation in a renal transplant recipient.
AB  - Surface antigen mutations of hepatitis B virus (HBV) may lead to immune escape
      and cause failure of immunization. In this report, the development of a chronic
      HBV infection in a vaccinated renal transplant recipient with pre-existing anti
      HBs antibody is documented. The sequencing data showed that the HBV strain
      carried five amino acid substitutions in the major hydrophilic region of the S
      protein, one (sS143L) located at the "a" determinant. A commercial HBsAg assay
      failed to detect the mutant antigen.

PMID- 17210269
TI  - Seroprevalence of human papillomavirus types 16 and 18 in the general population
      in Taiwan: implication for optimal age of human papillomavirus vaccination.
AB  - BACKGROUND: The optimal age for administration of recently approved prophylactic
      human papillomavirus (HPV) vaccines remains undetermined. OBJECTIVES: The aim of
      the study was to explore the age-specific seroprevalence of HPV 16 and 18 in the
      general population to design an HPV vaccination campaign for Taiwan. STUDY
      DESIGN: HPV seroprevalence was assessed by virus-like particle (VLP)-based ELISA
      in 1702 plasma samples collected in 1999. RESULTS: The sample population
      consisted of 1000 (58.8%) females and 702 (41.2%) males; age ranged from 17 days
      to 86 years. The age-specific distributions reveal a significant rise in HPV 16
      seropositivity commencing at 19-25 years of age and peaking at >60 years. The
      trend of seropositivity increase with age was also highly significant for HPV 18
      (P(Trend)<0.0001). Males had lower overall seroprevalence in gender comparison
      (7.6% versus 3.85% for HPV 16, 3.9% versus 2.71% for HPV 18), were older at
      seroconversion (19-25 years versus 26-30 years) with a more obvious
      seropositivity nadir in middle age. CONCLUSION: The age-specific seroprevalence
      of HPV 16 and 18 increases in young adults after the age of 18 years, with gender
      distribution varying. We conclude that the optimal age for universal HPV
      vaccination in Taiwan is 15 years or below.

PMID- 17210270
TI  - Acrimonious acronyms: CRMO, SAPHO and a sore shin.

PMID- 17210271
TI  - Differences in cardiorespiratory and neuromuscular responses between voluntary
      and stimulated contractions of the quadriceps femoris muscle.
AB  - The aim of this study was to compare respiratory gas exchange variables and
      muscle fatigue between equal-intensity (i.e., same force output)
      electrostimulated and voluntary contractions of the quadriceps muscle (46+/-10%
      of maximal voluntary force). Twelve healthy men served as volunteers. Oxygen
      consumption, ventilation and respiratory exchange ratio were recorded during the
      exercise bouts. Muscle fatigue was quantified as the exercise-induced reduction
      in maximal voluntary force. The average oxygen consumption (11+/-3 versus 8+/-2
      mL min(-1)kg(-1)), ventilation (23+/-4 versus 16+/-2 L min(-1)) and respiratory
      exchange ratio (0.96+/-0.02 versus 0.85+/-0.01) were significantly higher during
      electrostimulation compared with voluntary exercise (P<0.05-0.001). Maximal
      voluntary force decreased significantly after electrostimulation (-21+/-10%;
      P<0.001), while no changes were observed following voluntary exercise.
      Electrostimulation-resistance exercise of the quadriceps muscle elicited greater
      cardiorespiratory demand and muscle fatigue compared with voluntary contractions
      of the same intensity. These findings probably reflect differences in the
      patterns of motor unit recruitment between stimulated and voluntary contractions,
      despite equal force productions.

PMID- 17210272
TI  - Determination of treosulfan in plasma and urine by HPLC with refractometric
      detection; pharmacokinetic studies in children undergoing myeloablative treatment
      prior to haematopoietic stem cell transplantation.
AB  - A direct and selective HPLC method with refractometric detection was worked out
      for determination of treosulfan in plasma and urine of children. Before injection
      onto reverse phase column plasma samples with treosulfan and barbital (I.S.) were
      clarified using filtration. The mobile phase was composed of phosphate buffer, pH
      5 and acetonitrile. The linear range of the standard curve of treosulfan spanned
      concentrations of 10.0-2000.0 microg/ml and 50.0-10000.0 microg/ml in plasma and
      urine, respectively, and covered the levels found in biological fluids after
      infusion of the drug. The limit of detection amounted to 5 microg/ml for plasma
      and 25 microg/ml for urine. Intra- and inter-day precision and accuracy of the
      measurement fulfilled analytical criteria accepted in pharmacokinetic studies.
      Recovery of treosulfan as well as stability in biological fluids was also
      calculated. The validated method was successfully applied in pharmacokinetic
      studies of treosulfan administered to children prior to haematopoietic stem cell
      transplantation. Differences between pharmacokinetics of treosulfan in children
      and adults were also studied.

PMID- 17210273
TI  - Simultaneous quantification of opiates, amphetamines, cocaine and metabolites and
      diazepam and metabolite in a single hair sample using GC-MS.
AB  - A method is described for the simultaneous identification and quantification of
      opiates, amphetamines, cocainics, diazepam and nordiazepam from one hair extract
      (typically 10-50mg hair). After decontamination by washing with shampoo,
      dichloromethane, isopropanol and acetone, drugs were extracted using 0.1M HCl
      followed by SPE clean-up using mixed-mode extraction cartridges. The SPE extracts
      were submitted to a two-step derivatisation using MBTFA and MSTFA+1% TCMS and
      analysis was performed by GC-MS using both SIM and scan modes. Four deuterated
      standards were used to monitor 14 compounds. The limit of quantification was the
      total drug detected from the sample. This was 5 ng for amphetamines and 10 ng for
      remaining drugs which is equivalent to 0.1 and 0.2 ng/mg from a 50mg sample.
      Standard curves for the range 5-400 ng total drug concentration for all drugs had
      regression coefficients greater than 0.98. An authentic hair sample was used to
      validate the method and gave R.S.D.s <25% for both inter and intra-day
      reproducibility. The results of the analysis of hair taken from four patients
      attending a drug treatment clinic and six hair samples including head hair, pubic
      hair, axial hair and beard taken at post-mortem are presented.

PMID- 17210274
TI  - Issues in sleep and breathing.

PMID- 17210275
TI  - Epidemiology of sleep-related obstructive breathing.
AB  - The diagnosis of obstructive sleep apnoea syndrome (OSAS) and upper airway
      resistance syndrome (UARS) is based both on a combination of laboratory findings
      from whole-night sleep recordings and daytime symptoms. Due to the recent
      interest in breathing disturbances during sleep many prevalence studies have been
      performed within this field. There are, however, methodological difficulties in
      characterizing these syndromes in large populations; many of the studies have
      therefore been unable to present an overview of the complete syndromes but rather
      have focused on specific characteristics. In epidemiological research snoring
      and/or daytime sleepiness have often been used as markers of OSAS, while other
      studies have looked only on the respiratory disturbances or oxygen desaturation.
      Studies on the prevalence of OSAS based on polysomnography are reviewed here, as
      well as investigations where associated factors such as cardiovascular diseases
      and mortality were analysed. The interrelationships between snoring, daytime
      symptoms and laboratory findings are discussed. Gender, age, obesity, smoking,
      alcohol and ethnicity are all factors that influence the prevalence of OSAS. The
      data on associations between OSAS and cardiovascular disease or mortality are
      sometimes unrelated. Much of the discrepancy between different studies can be
      explained by the methodological difficulties connected with the definition of
      OSAS and also by the fact that the association between sleep-disordered breathing
      and cardiovascular outcome seems to be age-dependent.

PMID- 17210276
TI  - Weight loss as a treatment for obstructive sleep apnoea.
AB  - Obesity is a major health problem in well-developed societies. It is frequently
      associated with metabolic, cardiovascular and psychological comorbid conditions.
      Besides, it is known that obesity constitutes a risk factor for obstructive sleep
      apnoea (OSA). Weight loss has been evaluated as a treatment for OSA. We reviewed
      the nature of the link between obesity and OSA as well as the conservative and
      surgical therapeutic approaches of obesity. We consider the effectiveness of
      weight loss alone or combined with other modalities of treatment in OSA. We
      conclude that although weight loss is important and can facilitate the treatment
      of OSA, it can rarely cure it without being associated to classical techniques,
      such as nasal continuous positive airway pressure (nCPAP).

PMID- 17210277
TI  - Is changing the sleep environment enough? Current recommendations for SIDS.
AB  - Sudden infant death syndrome (SIDS or cot death) was the major cause of post
      neonatal infant death in many countries in the late 1970s and 1980s. There is now
      very strong evidence that public intervention campaigns targeting the prone
      sleeping position, which had been identified by epidemiological studies as a
      major risk factor, were followed by substantial falls in the rate of SIDS. In the
      present review we discuss the evidence on which current recommendations for the
      prevention of SIDS are based. The prone sleeping position is now clearly causally
      associated with SIDS. Further reductions in SIDS may be produced by recommending
      the back sleeping position as opposed to the side position. Maternal smoking in
      pregnancy and bed sharing by infants of mothers who smoke are also strongly
      associated with SIDS, but have been harder to influence. Paternal smoking has
      also been implicated, although the magnitude of the reported risk is small.
      Finally, breastfeeding, pacifier use and having the infant sharing the parents
      bedroom, but not the bed, may also reduce risk. Continued reductions in SIDS
      mortality will require innovative public health education to target these major
      risk factors, while building on the "back to sleep" approach.

PMID- 17210278
TI  - Brain structures and mechanisms involved in the control of cortical activation
      and wakefulness, with emphasis on the posterior hypothalamus and histaminergic
      neurons.
AB  - Wakefulness is a functional brain state that allows the performance of several
      "high brain functions", such as diverse behavioural, cognitive and emotional
      activities. Present knowledge at the whole animal or cellular level suggests that
      the maintenance of the cerebral cortex in this highly complex state necessitates
      the convergent and divergent activity of an ascending network within a large
      reticular zone, extending from the medulla to the forebrain and involving four
      major subcortical structures (the thalamus, basal forebrain, posterior
      hypothalamus and brainstem monoaminergic nuclei), their integral interconnections
      and several neurotransmitters, such as glutamate, acetylcholine, histamine and
      noradrenaline. In this mini-review, the importance of the thalamus, basal
      forebrain and brainstem monoaminergic neurons in wake control is briefly
      summarized, before turning our attention to the posterior hypothalamus and
      histaminergic neurons, which have been far less studied. Classical and recent
      experimental data are summarized, supporting the hypothesis that (1) the
      posterior hypothalamus constitutes one of the brain ascending activating systems
      and plays an important role in waking; (2) this function is mediated, in part, by
      histaminergic neurons, which constitute one of the excitatory sources for
      cortical activation during waking; (3) the mechanisms of histaminergic arousal
      involve both the ascending and descending projections of histaminergic neurons
      and their interactions with diverse neuronal populations, such as neurons in the
      pre-optic area and cholinergic neurons; and (4) other widespread-projecting
      neurons in the posterior hypothalamus also contribute to the tonic cortical
      activation during wakefulness and/or paradoxical sleep.

PMID- 17210279
TI  - Frederic Bremer 1892-1982: a pioneer in sleep research.
AB  - Frederic Bremer was one of the pioneer neurophysiologists who dedicated their
      career to understanding the neural mechanisms involved in the control of sleep
      wake regulation. This paper follows his career and his major achievements. We
      found that Bremer's interest in sleep resulted from his unexpected observations
      after transecting the brain at the midcollicular level in the "encephale isole"
      preparation. The sleep-like behaviour of the animal, accompanied by slow waves in
      the cortex, convinced him that sleep resulted from cortical deafferentation. He
      was further convinced that deafferentation was the cause of sleep when he found
      that transecting the brain at the medullary level did not much affect the sleep
      wake cycle. As we show, Bremer's views that sleep is a passive phenomenon imposed
      on the brain because of deafferentation was shared by most of his contemporaries.
      Years later Bremer admitted that he interpreted his experimental findings
      wrongly. He continued to investigate sleep using his preparations and made
      important contributions to understanding the relationships between the brainstem
      reticular formation and the basal forebrain hypnogenic centres, as well as the
      importance of light on these relationships.

PMID- 17210283
TI  - Research news and notes.

PMID- 17210284
TI  - Why is surgical neurology publishing a series on surgery for cerebral aneurysms?

PMID- 17210285
TI  - Microneurosurgical management of proximal middle cerebral artery aneurysms.
AB  - BACKGROUND: The M1As are located in the main trunk (M1) of the MCA, between the
      bifurcation of the ICA and the main bifurcation of M1. Proximal MCA aneurysms are
      often small and thin-walled, which makes their proper clipping tedious. There are
      few reports on their microsurgery. METHODS: This review, and the whole series on
      intracranial aneurysms, is mainly based on the personal microneurosurgical
      experience of the senior author (JH) in 2 Finnish centers (Helsinki and Kuopio),
      which serve, without selection, the catchment area in the southern and eastern
      Finland. RESULTS: These 2 centers have treated more than 10000 patients with
      aneurysm since 1953. We review the practical anatomy, preoperative planning, and
      avoidance of complications in the microsurgical dissection and clipping of M1As
      which form 7.4% of all intracranial and 14% of all MCA aneurysms in our patients.
      CONCLUSIONS: Proximal MCA aneurysms are often wide-necked and intimately
      connected to an M1 branch at its origin on M1, features that favor exosurgery
      rather than endosurgery. The direction and course of the parent and branching
      arteries and the orientation of the fundus are the most important factors
      affecting the efficacy and safety of clipping.

PMID- 17210286
TI  - Neuroprotection against surgically induced brain injury.
AB  - BACKGROUND: Neurosurgical procedures are carried out routinely in health
      institutions across the world. A key issue to be considered during neurosurgical
      interventions is that there is always an element of inevitable brain injury that
      results from the procedure itself because of the unique nature of the nervous
      system. Brain tissue at the periphery of the operative site is at risk of injury
      by various means, including incisions and direct trauma, electrocautery,
      hemorrhage, and retractor stretch. METHODS/RESULTS: In the present review, we
      will elaborate upon this surgically induced brain injury and also present a novel
      animal model to study it. In addition, we will summarize preliminary results
      obtained by pretreatment with PP1, an Src tyrosine kinase inhibitor reported to
      have neuroprotective properties in in vivo experimental studies. Any form of
      pretreatment to limit the damage to the susceptible functional brain tissue
      during neurosurgical procedures may have a significant impact on patient
      recovery. CONCLUSION: This brief review is intended to raise the question of
      'neuroprotection against surgically induced brain injury' in the neurosurgical
      scientific community and stimulate discussions.

PMID- 17210289
TI  - Cardiac complications after aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Cardiac complications are frequently encountered by neurointensivists
      caring for patients with SAH. Our aim was to better characterize the natural
      history of various cardiac abnormalities in this population. We sought to
      determine the risk factors for cardiac abnormalities, patient outcome, and impact
      of treatment type on cardiac abnormalities. METHODS: We performed a single center
      retrospective review of admissions of patients with aneurysmal SAH to the
      neurosurgical ICU in a large university hospital. Patient demographics, pertinent
      history, cardiac tests, hospital LOS, intervention type, and discharge outcome
      were collected. RESULTS: Data from 266 patients were available for analysis. Of
      these patients, 50% (n = 133) demonstrated cardiac abnormalities as indicated by
      abnormal EKG, ECHO, or troponin I. Only age was determined to be an independent
      statistically significant predictor of cardiac abnormality (P = .01). There was
      no difference in mortality between the cardiac abnormality and control groups (P
      = .33). However, there was increased morbidity in the cardiac abnormality group
      as demonstrated by worse discharge disposition, in addition to increased length
      of hospital stay (22.6 vs 17.1 days, P < .01). The incidence of cardiac
      abnormalities was the same among surgical and endovascular treatment groups.
      CONCLUSIONS: Cardiac abnormalities, including those that meet ACC criteria for
      MI, are common among patients with SAH. However, in contrast to cardiac events
      outside the context of SAH, these abnormalities do not increase mortality. They
      do, however, adversely affect discharge disposition and prolong hospital LOS. The
      type of aneurysm treatment does not affect the incidence or outcome of cardiac
      abnormalities.

PMID- 17210291
TI  - Efficacy of a direct puncture approach for anterior circulation aneurysms using a
      newly developed guiding catheter - especially for geriatric patients.
AB  - BACKGROUND: Endovascular surgery is being increasingly used as an alternative to
      craniotomy clipping surgery, especially for aged patients and complicated cases.
      However, tortuous atherosclerotic arteries sometimes interfere with advancement
      of catheters so that direct puncture may be necessary. Short guiding catheters
      for use with this approach have been newly developed, as discussed in this
      article. METHODS: One hundred twenty three anterior circulation aneurysms in 121
      patients were consecutively treated by endovascular coil embolization, of which
      42 (34%) were older than 70 years. RESULTS: With 21 aneurysms, coil embolization
      via the transfemoral approach failed, but all could be successfully treated with
      the direct puncture approach with minor complications such as 1 transient
      ischemic attack and 1 nonsymptomatic minor leakage. In the aged patients, the
      direct puncture approach with short guiding catheter resulted in complete
      obliteration of aneurysms in 20 (71%) of 28 with follow-up angiography.
      CONCLUSION: Direct puncture using newly developed short guiding catheters is an
      alternative to femoral approaches for patients with anterior circulation aneurysm
      with tortuous arteries and obvious atherosclerotic change at bifurcations of the
      common carotid artery.

PMID- 17210293
TI  - Asymptomatic carotid artery plaques: use of magnetic resonance imaging to
      characterize vulnerable plaques in 6 cases.
AB  - BACKGROUND: Echography is a convenient and noninvasive method of characterizing
      carotid artery plaques. However, recent reports suggest that multisequential MR
      imaging may yield better data regarding the instability of asymptomatic carotid
      artery plaques. Therefore, the goal of the present study was to show the useful
      information for asymptomatic carotid artery plaque. METHODS: A total of 6
      patients (5 men, 1 woman; age range, 62-76 years; mean age, 69.2 years) with
      carotid artery plaques, which were detected during medical check-up using carotid
      MR angiography and/or echography, underwent MR imaging. Two-dimensional TOF MR
      angiography, T1WI, and fat-suppressed, cardiac-gated, black-blood proton density
      image, and T2WI were obtained with a 1.5-T MR imager. All plaques underwent
      carotid endarterectomy and histological examination. RESULTS: The MR imaging
      demonstrated high signals in at least one modality in 4 of 7 plaques. In the
      remaining 3 patients, MR imaging detected partial-high signals, which
      corresponded to histologically confirmed partial lipid core or hemorrhagic
      components in the fibrous tissues The TOF MR imaging showed 2 cases of thin
      fibrous caps, and MR imaging also showed a large mural thrombus in 1 patient.
      CONCLUSIONS: Magnetic resonance imaging was useful in characterizing factors
      associated with plaque instability in patients with asymptomatic carotid artery
      plaques and may help guide therapeutic strategies for asymptomatic carotid artery
      plaques.

PMID- 17210294
TI  - Electromagnetic field system for transsphenoidal surgery on recurrent pituitary
      lesions - technical note.
AB  - BACKGROUND: Post operative scar tissue makes transsphenoidal surgery for
      recurrent pituitary lesions very difficult. However, with the use of a new
      cautery system, known as the EMF system, we were able to perform the surgical
      procedures with relative ease. In this article, we report the advantages and
      clinical applications of this new instrument in transnasal reoperation. METHODS:
      The EMF system generates a high frequency current of 13.56 MHz that is focused on
      the target. This enables it to coagulate, cut, and vaporize tissue in a pinpoint
      fashion. The bayonet and pencil-type hand pieces of the EMF system are slim, and
      the tips of the probe are flexible. This enables the surgeon to easily reach deep
      narrow spaces. We have used the EMF system for transsphenoidal surgery on
      recurrent pituitary lesions in 18 patients. The system was used to cut and
      vaporize scar tissue and vaporize firm and fibrotic tumor tissue. RESULTS: During
      surgery, the system could easily cut and vaporize scarred tissues in the nasal
      cavity, the sphenoid sinus, and the sella, without damage to the surrounding
      tissue. In addition, in 3 patients who had extremely fibrotic and firm tumors, we
      were able to easily vaporize the tumor with safety. CONCLUSIONS: The EMF system
      enables the surgeon to cut and vaporize tissue with ease and with minimal injury
      to the surrounding structures. It was particularly valuable in the resection of
      firm tumors. It may also shorten the operating time because of quick vaporization
      of the firm tissue.

PMID- 17210297
TI  - Distal anterior choroidal artery aneurysms.
AB  - BACKGROUND: Distal AChoA aneurysms are quite rare. Only 12 operated cases have
      been reported in the English medical literature. Treatment of these aneurysms is
      also difficult because of their deep location, small size, and angioarchitecture.
      METHODS: The authors report 2 additional patients with aneurysms, arising from
      the distal AChoA and located within the temporal horn of the lateral ventricle.
      In the first patient, the aneurysm could also be visualized with CTA, which is
      the first demonstration in the literature. RESULTS: The aneurysms were explored
      and resected via a transtemporal/ventricular approach in both patients. One
      patient was discharged as neurologically intact and the other died because of
      severe vasospasm. CONCLUSIONS: The conclusions drawn from our experience and a
      comprehensive review of the literature include the following: (1) A distal AChoA
      aneurysm should be considered in patients with isolated medial temporal
      intracerebral hematoma with intraventricular extension. (2) These aneurysms are
      frequently very small (<5 mm). Therefore, they cannot be detected on initial
      angiograms in some cases. (3) These small aneurysms cannot be usually clipped
      without sacrificing the parent artery. (4) Sacrificing distal AChoA (beyond the
      plexal point) does not usually cause any neurological deficit, but, whenever
      possible, this artery should be preserved.

PMID- 17210300
TI  - Survival analysis of 459 adult patients with primary spinal cancer in England and
      Wales: a population-based study.
AB  - BACKGROUND: Primary spinal gliomas are rare. Because data from the Cancer
      Registry of England and Wales covered larger numbers of patients and longer
      durations of follow-up, our objective was to define prognostic factors for
      survival at a national population level. METHODS: From 1971 to 1995, data on 459
      adult patients (age, >15 years) with primary spinal cancer from the Cancer
      Registry of England and Wales were analyzed. Median survival and CSRs with
      respect to 7 variables (age, sex, morphology, WHO grade, socioeconomic status,
      geographic region, and period of diagnosis) were calculated using the Kaplan
      Meier method. Cox regression was performed for estimating HRs for death. RESULTS:
      The median survival and the 1-, 5-, and 10-year CSRs for the population were 10.2
      years, 78.7%, 59.7%, and 50.5%, respectively. Univariate analysis revealed that
      age at diagnosis, morphology, WHO grade, and period of diagnosis affected the
      CSR. Multivariate analysis demonstrated 3 factors influencing survival: older age
      (ie, >60 years; HR = 2.67; P < .001), non-ependymomas (HR = 3.51; P < .001), and
      high-grade tumors (HR = 3.01; P < .001). The improved survival in recent periods
      was associated with an increased number of diagnosed ependymomas. CONCLUSION:
      This study identifies old age, non-ependymomas, and high-grade tumors as negative
      prognostic factors for patient survival. The results from this population-based
      study are very helpful for comparison with those of other hospital-based studies
      and for public health purposes.

PMID- 17210302
TI  - Sellar repair with resorbable polyglactin acid sheet and fibrin glue in
      endoscopic endonasal transsphenoidal surgery.
AB  - BACKGROUND: Cerebrospinal fluid leakage after transsphenoidal surgery represents
      a serious problem. Various methods to prevent postoperative CSF leakage are
      available, but immediate and tight dural closure is still difficult. The efficacy
      of a novel sellar repair was described. METHODS: The sellar repair using
      absorbable PGA sheet and fibrin glue was applied to 18 consecutive patients with
      sellar tumors that include 13 pituitary adenomas, 2 craniopharyngiomas, 2
      Rathke's cleft cysts, and 1 meningioma within 135 patients who were treated with
      endoscopic endonasal transsphenoidal approach. The reaction speed and strength
      between PGA sheets and fibrin glue were examined in vitro. RESULTS: Polyglactin
      acid sheets were adhered to the rabbit skin with fibrin glue within 3 minutes and
      withstood a pressure of more than 220 mm Hg. Postoperative CSF leakage of the
      patients was not observed in any patients, and excellent adhesion of the PGA
      sheets to surrounding mucosa was estimated by endoscopic observation after the
      surgery. CONCLUSIONS: Repair of the sellar floor with PGA sheet and fibrin glue
      is a safe and effective method to prevent postoperative CSF leakage, which
      decreases the necessity for lumbar drainage after the operation.

PMID- 17210304
TI  - Spinal gout in a renal transplant patient: a case report and literature review.
AB  - BACKGROUND: Gout in the axial spine is rare. We present a case report on a renal
      transplant patient who developed fever and acute back pain at the L5 through S1
      level secondary to sodium urate deposits. We review the literature on this rare
      disease and propose a management algorithm based on a resulting analysis. CASE
      DESCRIPTION: A 37-year-old man with a history of gout and a renal transplant for
      IgA nephropathy presented with acute back pain and fever without evidence of
      neurological deficits. Magnetic resonance imaging revealed a uniformly contrast
      enhancing infiltrative process involving the right pedicle, lamina, and inferior
      facet of the L5 vertebra. Computed tomography-guided needle biopsy revealed a
      friable white tissue consistent with sodium urate crystals. Conservative
      treatment with steroids and narcotics was used with good symptomatic relief.
      CONCLUSION: Although few cases of gout involving the spine have been reported,
      its prevalence is likely grossly underestimated. Most patients have a history of
      gout and have elevated levels of serum urate level on presentation. The disease
      most commonly involves the lumbar spine. Patients usually have neurological
      deficits on presentation, and surgical decompression produces favorable outcomes.
      However, conservative medical management is appropriate for those with back pain
      only. Aggressive control of hyperuricemia is essential regardless of the method
      of treatment.

PMID- 17210306
TI  - Treatment of intramedullary spinal cysticercosis: report of 2 cases and review of
      literature.
AB  - BACKGROUND: NCC, Taenia solium involvement in the central nervous system, is one
      of the most common parasitic diseases. Spinal IMC is one of the rarest forms of
      NCC. CASE DESCRIPTION: We report 2 cases (an 8-year-old child and a 35-year-old
      woman) of spinal IMC. Both cysts were dorsal in location. MRI was diagnostic in
      both cases. One case was treated surgically because of acute presentation. The
      other cyst healed with treatment with albendazole. Both patients had good
      clinical outcomes. CONCLUSION: With medical management, IMC may take 1 year to
      resolve on MRI.

PMID- 17210309
TI  - Evaluation of platybasia in patients with idiopathic trigeminal neuralgia.
AB  - BACKGROUND: Vascular compression of the trigeminal nerve is generally accepted as
      the primary source causing TN. To date, skull base bone deformity associated with
      ITN has been reported in only a number of case reports. The aim of the present
      study was to investigate one such skull base deformity, platybasia, in ITN
      patients in comparison with a randomized control population. METHODS: Basal angle
      values reflecting the development of platybasia were measured in 25 patients with
      ITN and compared with the measurements in 25 control subjects. RESULTS: Basal
      angle measured to investigate the existence of platybasia was found significantly
      wider in the ITN group (t = 3.90; P < .001), although platybasia was present in
      only 10 patients. Moreover, the average angle was also greater in the study group
      than in the control group, and the difference was statistically significant.
      Platybasia was found in 10 patients, whereas it was detected in only 2 control
      individuals; difference in platybasia incidence between the 2 groups was also
      statistically significant (chi(2) = 7.01; P < .01). CONCLUSION: Our data
      demonstrated that platybasia affecting the bony walls of the posterior fossa may
      play an important role in the pathogenesis if vascular abnormalities causing TN.

PMID- 17210311
TI  - Oculomotor nerve schwannoma located in the oculomotor cistern.
AB  - BACKGROUND: OSs are extremely rare tumors, most often located in the
      interpeduncular cistern or the CS. We report an OS located predominantly within
      the oculomotor cistern, the arachnoid sac that surrounds the nerve for a short
      distance in the roof of the CS. We discuss a possible growth pattern for
      cavernous OSs. CASE DESCRIPTION: We report the case of a 34-year-old woman
      presenting with a right oculomotor nerve palsy. Magnetic resonance imaging
      revealed a mass within the borders of the roof of the CS extending forward toward
      the superior orbital fissure. A right pterional approach was undertaken, and the
      roof of the CS was opened just above the oculomotor nerve toward the superior
      orbital fissure. Although the part of the OS inside the oculomotor cistern was
      excised completely while preserving the anatomical continuity of the nerve, a
      subtotal removal was performed for the more anterior part of the tumor toward the
      superior orbital fissure. At 5 months follow-up, her third nerve paresis had
      improved dramatically. CONCLUSIONS: Resection of cavernous OSs within the
      oculomotor cistern, where the third nerve is clearly separated from the adjacent
      neurovascular structures, is feasible with functional preservation of the nerve.
      The chance of occurrence of the nerve palsy may increase as the resection
      proceeds more anteriorly toward the superior orbital fissure.

PMID- 17210313
TI  - Giant arteriovenous malformation associated with unilateral moyamoya disease in a
      child: case report.
AB  - BACKGROUND: Cerebral AVMs associated with definite or probable moyamoya disease
      is a very rare situation, and the association between them is unclear. CASE
      DESCRIPTION: An 8-year-old boy presented with repeated transient motor weakness
      in the left arm and leg for 1 year. On his admission, physical examination and
      neuropsychological testing showed no exact neurological deficits. Magnetic
      resonance imaging showed a giant AVM in the right basal ganglia and thalamus.
      Angiography revealed occlusion of left ICA and bilateral PCA with well-developed
      basal collateral vessels. A giant AVM was also noticed in angiography, which was
      filled by basal collateral vessels from both left anterior circulation and
      posterior circulation. The diagnosis of unilateral moyamoya disease combined with
      a Spetzler-Martin grade V AVM was made. The patient was managed nonoperatively
      and discharged with close follow-up. CONCLUSION: We present a rare case of giant
      AVM-associated with unilateral moyamoya disease, and giant AVM makes planning any
      aggressive treatments difficult.

PMID- 17210315
TI  - Resolution of a fourth ventricle epithelial cyst after ventriculoperitoneal
      shunting: case report.
AB  - BACKGROUND: Symptomatic cysts of epithelial origin occurring in the fourth
      ventricle are very rare. When such a cyst is encountered, the treatment strategy
      includes surgical removal or fenestration of the cyst into subarachnoid space.
      CASE 1: A 23-year-old male was diagnosed as having a cyst located in the fourth
      ventricle causing hydrocephalus; the patient underwent cyst removal via
      craniotomy. The histopathologic diagnosis was neuroepithelial cyst. Because
      clinical and neuroradiological findings persisted, he underwent VP shunting. The
      cyst disappeared and did not recur. CASE 2: A 54-year-old woman was diagnosed as
      having a cystic mass in the fourth ventricle and dilatation of the ventricles.
      Magnetic resonance imaging showed the same findings as those of the first case.
      The patient refused craniotomy for total mass excision. Therefore, a VP shunt was
      applied. Postoperatively, the clinical findings and hydrocephalus improved, and
      complete disappearance of the cystic mass was observed unexpectedly. Both cases
      had 2 years of follow-up. CONCLUSION: There is no proven mechanism to explain
      resolution of fourth ventricle cysts after a supratentorial VP shunting. We
      hypothesize that disappearance of the cyst could result from rupture of its wall
      because of pressure gradient, which might be facilitated by a VP shunt. The
      current report should not be taken as an argument against cyst removal, which is
      the established way of treatment. However, considering that the pathogenesis and
      pathophysiology of these cysts are unclear, VP shunting should be considered
      especially for recurrent cases accompanied by hydrocephalus.

PMID- 17210317
TI  - De novo aneurysm formation and regression after brain arteriovenous malformation
      embolization: case report.
AB  - BACKGROUND: The formation of de novo aneurysms is a known complication of vessel
      occlusion (Wright RL, Sweet WH. Carotid or vertebral occlusion in the treatment
      of intracranial aneurysms: value of early and late readings of carotid and
      retinal pressures. Clin Neurosurg 1962:9;163-192). Aneurysms most commonly
      develop on newly formed primary collateral routes as a result of increased flow
      through these collaterals. Development of aneurysms is not commonly seen in
      vessels whose flow has been directly decreased by therapeutic or natural
      occlusion. CASE DESCRIPTION: A 53-year-old woman with an intracerebral hemorrhage
      underwent cerebral angiography which demonstrated a right parietal AVM. An
      enlarged right ACA gave rise to 3 direct feeding pedicles. Leptomeningeal
      collaterals from the right MCA as well as the right PCA also gave collateral
      supply to the AVM. The lesion had superficial drainage into the superior sagittal
      sinus and deep venous drainage into the right posterior pericallosal vein. No
      feeding artery aneurysms or intranidal aneurysms were present. Treatment plan
      included preoperative embolization followed by surgical resection. CONCLUSION: To
      our knowledge, this is the first reported case of a de novo aneurysm forming and
      regressing in an artery hemodynamically related to an embolized AVM. The short
      timescale of its development (6 weeks) is also noteworthy. The spontaneous
      regression suggests that at least some aneurysms forming in vessels after abrupt
      decrease in distal runoff may have a self-limited course. Such lesions may do
      best if not subjected to direct endovascular or surgical treatment.

PMID- 17210319
TI  - Extracranial meningioma in the vicinity of the temporal bone: a difficult
      preoperative diagnosis.
AB  - BACKGROUND: Extracranial meningioma is a rare tumor, and most of the time only
      after histopathologic examination is diagnosis possible. CASE DESCRIPTION: A 40
      year-old right-handed woman presented with progressive swelling over the right
      side of the forehead and temporal region associated with proptosis and visual
      loss. Incisional biopsy of the lesion was reported as spindle cell tumor.
      Computed tomography scan showed large enhancing predominantly extracranial lesion
      located in the right anterior frontotemporal region extending into the
      infratemporal fossa and a relatively thin sheet of tumor on the intracranial
      aspect of the thickened temporal. Intraoperative impression was malignant tumor
      involving the temporalis muscle, and a near total excision of the lesion was
      performed. Histopathologic features were suggestive of meningothelial meningioma
      arising from the temporal bone with predominant extracranial extension.
      CONCLUSION: Preoperative suspicion of a meningioma in this patient would have
      resulted in a more aggressive surgical approach as these lesions are relatively
      benign with indolent course.

PMID- 17210320
TI  - "Boom boom" surgery.

PMID- 17210321
TI  - Re: Leadership vs. consensus (Ausman JI. Surg Neurol 2006;66:548-549).

PMID- 17210323
TI  - The essential and ethical expert: serving as a medical expert witness in the 21st
      century.

PMID- 17210324
TI  - American Academy of Otolaryngic Allergy CME report: allergy; scope of knowledge.

PMID- 17210325
TI  - Extracts from The Cochrane Library: antihistamines and/or decongestants for
      otitis media with effusion (OME) in children.
AB  - The "Cochrane Corner" is a quarterly section in the Journal that highlights
      systematic reviews relevant to otolaryngology-head and neck surgery, with invited
      commentary to highlight implications for clinical decision making. This
      installment features a Cochrane Review entitled "Antihistamines and/or
      decongestants for otitis media with effusion (OME) in children," which recommends
      against treatment because of no demonstrable benefits but significant potential
      for harm.

PMID- 17210326
TI  - Practical guides to understanding sample size and minimal clinically important
      difference (MCID).

PMID- 17210327
TI  - Otitis media in adults as a symptom of gastroesophageal reflux.
AB  - OBJECTIVE: To investigate the clinical relationship between gastroesophageal
      reflux (GER) and otitis media with effusion (OME) in adults. STUDY DESIGN AND
      SETTING: Sixty patients with OME with unknown causes were asked to answer a new
      questionnaire specific for the diagnosis of GER disease; pepsinogen (PG) levels
      in their middle-ear effusions (MEEs) were measured. RESULTS: The percentage of
      patients with high PG concentrations in their MEEs was significantly higher in
      those with questionnaire-positive GER than in those with questionnaire-negative
      GER. OME was present bilaterally in a significantly higher percentage of patients
      with questionnaire-positive GER. The PG levels decreased in some of the patients
      after receiving proton pump inhibitors, which also decreased the symptoms of GER.
      CONCLUSION: The presence of PG in MEEs supports the existence of GER; treatment
      for GER should be considered in patients with ear complaints, especially in those
      who have GER-related symptoms.

PMID- 17210328
TI  - Clinical and biochemical factors that affect DPOAE expressions in children with
      middle ear effusion.
AB  - OBJECTIVES: To evaluate the clinical and biochemical characteristics of middle
      ear effusion (MEE) that affect distortion product otoacoustic emissions (DPOAE)
      responsiveness and to investigate the possible role of DPOAE as a tool to know
      the characteristics of MEE preoperatively. STUDY DESIGN AND SETTING: Prospective
      analysis of children with MEE effusion in a tertiary referral center. DPOAE
      results were compared with other audiologic tests, the character, amount of MEE,
      the amount of total protein, and TNF-alpha in the effusion. RESULTS: The negative
      DPOAE with MEE group had much more thick mucous fluid in their middle ears than
      that of positive DPOAE with MEE group. The levels of total protein and TNF-alpha
      in MEE were significantly higher in the negative DPOAE group than those of the
      positive DPOAE group (P < 0.01). CONCLUSIONS AND SIGNIFICANCE: The measurement of
      DPOAE in the children with MEE may predict the amount and the characteristics of
      MEE, which may help to decide the treatment methods.

PMID- 17210329
TI  - Effects of the subcranial approach on facial growth and development.
AB  - OBJECTIVE: To analyze the long-term effects of subcranial surgery for anterior
      skull base tumors on facial growth. STUDY DESIGN AND SETTING: Retrospective study
      (1994 to 2004) in a university-affiliated hospital. Of 108 patients who underwent
      a subcranial surgical approach for anterior skull base tumors, six adolescents
      and five young adults fulfilled study entry criteria for age and follow-up data
      availability (mean, 3.2 +/- 2 years). Cephalometric x-ray films monitored
      postoperative facial growth. Anteriorly and posteriorly measured horizontal and
      vertical maxillary growth were compared with normal values. RESULTS: All subjects
      had superiorly positioned maxillae (shorter in patients with long-standing
      pathologies). The upper incisor teeth were proclined relative to the cranial base
      reference planes. All cephalometric changes were within a 10 percent deviation of
      normal values. CONCLUSIONS: Subcranial surgery for these tumors minimally affects
      vertical facial skeleton growth. Early surgery is essential for unaffected
      horizontal growth. SIGNIFICANCE: Guidelines for anterior skull base tumor surgery
      in adolescents and young adults.

PMID- 17210330
TI  - Velopharyngeal insufficiency in hemifacial microsomia: analysis of correlated
      factors.
AB  - OBJECTIVE: To investigate the incidence of unilateral hypodynamic palate (UHP)
      and velopharyngeal insufficiency (VPI) in hemifacial microsomia (HFM), and to
      determine the dysmorphic manifestations having significant associations with
      UHP/VPI in HFM. STUDY DESIGN: This was a nonrandomized study of 48 patients with
      unilateral HFM without cleft palate. The correlation between each anomaly and
      UHP/VPI was analyzed statistically. In addition, we observed 4 HFM patients with
      cleft palate to examine the influence on cleft palate speech. RESULTS: The
      incidence of UHP in HFM was 50.0% and that of VPI was 14.6%. All the VPI patients
      had UHP. Severe micrognathia and soft tissue deficiency, macrostomia, and mental
      retardation were significant risk factors for developing VPI in HFM. Moreover,
      UHP exacerbated speech in HFM with cleft lip and palate. CONCLUSIONS: Significant
      correlations were detected between VPI and HFM. This finding should be helpful in
      the overall management of HFM.

PMID- 17210331
TI  - Endoscopic versus external repair of orbital blowout fractures.
AB  - OBJECTIVES: This study evaluates the usefulness of endoscopic repair compared to
      external repair in the treatment of blowout fracture (BOF) of the orbit. STUDY
      DESIGN AND SETTING: This retrospective study comprised 100 patients who had had
      surgical repair of orbital BOF since 1992. Forty-eight of the 100 had undergone
      endoscopic repair, 48 patients had had external repair, and four patients
      underwent surgery that combined the two approaches. The two basic approaches were
      evaluated and compared with respect to technique, results and complications.
      RESULTS: Endoscopically, transnasal and transantral approaches had been used for
      reduction and support of fractured medial and inferior walls, respectively. In
      the external approach, various transorbital incisions were made and the fractured
      wall was repaired with alloplastic or autologous materials. Complete or partial
      resolution of preoperative diplopia was achieved in 94% of the endoscopic group
      and 83% of the external group (NS). Enophthalmos was improved in 89% of the
      endoscopic group and 76% of the external group (NS). Though the endoscopic group
      had no significant complications, the external group had ectropions, significant
      facial scars, extrusion of inserted Medpor, and intra-orbital hematoma.
      CONCLUSIONS: Endoscopic repair appears to be a safe and effective technique for
      the treatment of BOF of the orbit.

PMID- 17210332
TI  - Propofol versus sevoflurane: bleeding in endoscopic sinus surgery.
AB  - OBJECTIVE: Reduction of intraoperative bleeding is desirable to improve
      intraoperative visibility and to avoid complications. STUDY DESIGN: Prospective,
      controlled, randomized, double-blinded study. SETTING: Inclusion criteria were
      chronic rhinosinusitis with nasal polyps that involved all paranasal sinuses,
      Lund-CT score > or =12, and double-blind preoperative randomization of narcotics.
      Exclusion criteria included abnormal coagulation, perioperative blood pressure
      outside the range of 70 to 140 mmHg systolic and 50 to 90 mmHg diastolic and
      perioperative medication. Total blood loss (mL), blood loss per minute (mL/min),
      platelet function, and parameter for endoscopic vision were evaluated. RESULTS:
      Forty-six patients (22 sedated with sevoflurane/fentanyl, 24 sedated with
      propofol/fentanyl) completed the study. Total blood loss (300.1 +/- 168.5
      mL/276.9 +/- 201.3 mL), blood loss per minute, and endoscopic vision showed no
      group difference. Platelet function was significantly impaired 45 minutes after
      onset of surgery in both groups, but more pronounced after propofol anesthesia.
      CONCLUSION: Under conditions of balanced circulatory parameter, equal blood loss
      and endoscopic vision can be achieved with both tested anesthetic regimens.
      During extended operations demonstrated thrombocyte impairment by propofol may
      become clinically relevant.

PMID- 17210333
TI  - Autonomic nervous system evaluation in allergic rhinitis.
AB  - OBJECTIVES: To evaluate the relationship between allergic rhinitis (AR) and
      autonomic nervous system (ANS) dysfunction. METHODS: Quantitative ANS testing was
      completed in 10 patients with AR confirmed by clinical findings and allergy
      testing. This data was compared to 16 age-matched controls. RESULTS: ANS scores
      were significantly abnormal in AR patients when compared to normal controls. The
      composite autonomic scale score for the AR group was significantly impaired when
      compared to controls (1.6 vs 0.63, P < 0.0001). Additionally, subscore values
      quantifying the level of dysfunction within the sympathetic nervous system (1.0
      for sudomotor and 0.5 adrenergic) were found to be significantly different (P <
      0.0001 and 0.018). The mean subscore value quantifying the level of dysfunction
      within the parasympathetic system (cardiovagal) was not found to be significantly
      different from controls (P = 0.38). CONCLUSIONS: ANS dysfunction, specifically
      sympathetic hypofunction, was identified in all of the allergic rhinitis patients
      studied. Further characterization of the type of ANS abnormality may allow the
      development of novel pharmacologic therapies for these disorders.

PMID- 17210334
TI  - Rhinitis medicamentosa: electron microscopic changes of human nasal mucosa.
AB  - OBJECTIVE: Prolonged application of nasal vasoconstrictors causes rhinitis
      medicamentosa (RM). Nasal obstruction is induced by rebound swelling when the
      decongestive effect has disappeared. The aim of this study was to demonstrate
      ultrastructural changes in RM. STUDY DESIGN AND SETTING: Tissue samples of
      inferior turbinates from 22 patients with RM and 10 patients without rhinitis
      were taken during nasal surgery. Ultrathin sections were investigated by using a
      transmission electron microscope (TEM). RESULTS: The TEM findings revealed severe
      epithelial damages such as loss of ciliated cells. In the subepithelial region,
      the vascular endothelium showed gaps and ruptures of basal lamina. CONCLUSION: RM
      is a drug-induced damage of human nasal mucosa. Loss and destruction of ciliated
      epithelial cells are the morphologic correlation of the disturbed mucociliary
      clearance. In addition, vascular endothelium revealed ultrastructural changes.
      This could be caused by an increased vascular permeability with consecutive
      interstitial edema. SIGNIFICANCE: This study demonstrated new morphological
      aspects of rhinitis medicamentosa.

PMID- 17210335
TI  - Hypertonic saline alters electrical barrier of the airway epithelium.
AB  - OBJECTIVE: The effect of tonicity changes in nebulizer solutions and irrigations
      on nasal mucosa is not well known. The present study aims to determine the basic
      mechanism of hypertonic solution on airway epithelial barrier. STUDY DESIGN AND
      SETTING: We investigated the electrical potential difference (PD) that is
      influenced by both active transport and the transepithelial electrical resistance
      of the epithelial mucosa in the human nose in vivo. The short circuit current
      (SCC) revealed net ion transport across the epithelium in the guinea pig trachea
      in vitro. Finally, the size dependency of macromolecules across the tracheal
      mucosa was determined in vitro using FITC-labeled dextrans of different sizes.
      RESULTS: PD was significantly decreased after topical application of hypertonic
      solution both in human and in guinea pig nose. SCC was significantly decreased
      after application of hypertonic solution. The transport of these dextrans from
      the basolateral to the apical side was not increased significantly after apical
      application of hypertonic saline. CONCLUSIONS: Hypertonic saline enhances the
      electrical permeability of the airway epithelial mucosa but not transport of
      macromolecule in the short term.

PMID- 17210336
TI  - Otosyphilis: a review of 85 cases.
AB  - OBJECTIVE: To review the clinical manifestations and the follow-up hearing
      results of the treatment modalities in the patients with otosyphilis. STUDY
      DESIGN AND SETTINGS: A retrospective review between 1984 and 2000 at a university
      hospital. Patients who presented with cochleovestibular symptoms and were
      confirmed seropositive for specific treponemal tests were included. Excluded were
      patients older than 70, or who had other identified causes of cochleovestibular
      symptoms. RESULTS: Subjects included 56 males and 29 females with an average age
      of 59.5 years (range, 40 to 70). Common presenting symptoms included hearing loss
      (90.6%), tinnitus (72.9%), and vertigo (52.9%). The cerebrospinal fluid analysis
      was positive in 5.4%. The overall respective hearing results in the short- and
      long-term follow-up were improved or stable in 93.4% and 83.3% of patients. Even
      though adding steroids and neurosyphilis regimens tended to improve and stabilize
      hearing, the results were not statistically significant among treatment
      modalities. CONCLUSION: Further study about hearing outcomes among treatment
      modalities is suggested.

PMID- 17210337
TI  - A pilot clinical trial of the effects of coenzyme Q10 on chronic tinnitus aurium.
AB  - OBJECTIVE: To determine the short-term effects of coenzyme Q10 (CoQ10) on the
      antioxidative status and tinnitus expression in patients with chronic tinnitus
      aurium. STUDY DESIGN: A 16-week prospective nonrandomized clinical trial (n =
      20). Tinnitus and Short Form-36 Questionnaires (TQ/SF-36) were evaluated together
      with the plasma concentrations of CoQ10, malondialdehyde, and the total
      antioxidant status. RESULTS: The mean plasma CoQ10 concentration rose under
      external CoQ10 supply and remained elevated after medication stopped without
      overall effects on the tinnitus score. However, in a subgroup of 7 patients with
      low initial plasma CoQ10 concentration and significant increase in the plasma
      CoQ10 level, a clear decrease in the TQ score was observed. CONCLUSION: In
      patients with a low plasma CoQ10 concentration, CoQ10 supply may decrease the
      tinnitus expression. SIGNIFICANCE: This is the first study to examine the effect
      of CoQ10 in chronic tinnitus aurium.

PMID- 17210338
TI  - Hearing threshold shift measured by otoacoustic emissions after shooting noise
      exposure in soldiers using hearing protectors.
AB  - OBJECTIVE: The aim of the study was to assess the influence of short-term impulse
      noise to temporary threshold shift in soldiers using hearing protectors. STUDY
      DESIGN AND SETTING: The study included 80 subjects with correct tympanic membrane
      and thresholds measured by pure-tone audiometry less than 20 dB. There were two
      groups: 40 soldiers protected during shooting and 40 young males who didn't
      shoot. TEOAE were performed by ILO 292 Echoport Otodynamics device 3 to 5 minutes
      before shooting and 2 minutes and 1, 2, and 3 hours after shooting. RESULTS:
      Short-term exposure to impulse noise generated by five gunshots from the rifle
      kbk AKMS hasn't induced temporary threshold shift of hearing for chosen
      frequencies in soldiers using hearing protectors. Spectral analysis for chosen
      frequencies revealed that measurement reproducibility, stimuli level, and probe
      stability appeared to be comparable and repeatable. CONCLUSION: Our results show
      that the use of hearing protectors safeguarded against impulse noise.
      SIGNIFICANCE: The use of earmuffs is strongly recommended because they seem to
      sufficiently attenuate shooting noise.

PMID- 17210339
TI  - Audiovestibular disturbance in patients with systemic lupus erythematosus.
AB  - OBJECTIVE: The aim of this study was to evaluate the audiovestibular disturbance
      in patients with systemic lupus erythematosus (SLE). STUDY DESIGN AND SETTING:
      Twenty-eight patients with SLE and 28 healthy control subjects were included.
      Pure-tone audiometry, impedance audiometry, and electronystagmography (ENG) were
      used for baseline evaluation. Laboratory tests were carried out. Cranial and
      brain stem magnetic resonance imagings (MRI) were undertaken. RESULTS: Nineteen
      (67%) patients reported audiovestibular symptoms. Sensorineural hearing loss was
      found in 6 (21%) patients. Abnormal results on ENG were significantly higher
      (50%) (P < 0.01). Abnormal laboratory data were available from 26 patients (P <
      0.05). MRI did not show any pathosis. CONCLUSION: The audiovestibular
      disturbances in SLE are more prevalent than previously recognized. Although no
      cause and effect relationship can be established by this type of study, it
      appears that a relationship exists. SIGNIFICANCE: Audiologic research should be
      directed toward routine, pure tone audiometry, and ENG assessment for patients
      with SLE to enable crucial treatment.

PMID- 17210340
TI  - Bilateral versus unilateral sudden sensorineural hearing loss.
AB  - OBJECTIVES: To analyze the clinical characteristics and treatment results between
      bilateral (bi-) and unilateral (uni-) sudden sensorineural hearing loss (SSNHL).
      STUDY DESIGN AND SETTING: A retrospective study. METHODS: Three hundred twenty
      four patients with SSNHL were classified into two groups; simultaneous bi-SSNHL
      (n = 16) and uni-SSNHL (n = 308). We compared clinical characteristics, medical
      history, hearing level, and treatment results between the 2 groups. RESULTS: The
      incidence of bi-SSNHL was 4.9 percent of overall patients with SSNHL. Bi-SSNHL
      occurs more commonly in patients of older age, with preexisting diabetes
      mellitus, and lipid panel abnormalities compared with uni-SSNHL. Ten patients
      (62.5%) in the bi-SSNHL group showed hearing recovery in 1 or both ears compared
      with 56.5 percent of patients with uni-SSNHL. Only 12 (37.5%) of all 32 ears
      recovered in bi-SSNHL, which was significantly lower than in uni-SSNHL.
      CONCLUSION: Bi-SSNHL has a very low incidence and lower recovery rate than uni
      SSNHL. Recognition of similarities and differences between bilateral and
      unilateral SSNHL can help in counseling and managing the patients.

PMID- 17210341
TI  - Alcoholism, depression, and abnormal cognition in head and neck cancer: a pilot
      study.
AB  - OBJECTIVE: To determine prevalence of alcohol abuse and dependency, depression,
      and cognitive impairment in presurgical head and neck cancer patients. STUDY
      DESIGN: Standardized testing by diagnostic interview was used to determine major
      depression and alcoholism. Mattis Dementia Rating Scale examined cognitive
      ability preoperatively. Twenty-four patients with advanced head and neck cancer
      participated. SETTING: University hospital. RESULTS: A total of 63.6% met
      criteria for alcohol abuse and 62 percent for alcohol dependence; 26.1 % of
      patients met criteria for major depression. Testing in multiple subsets of
      cognitive function demonstrated measurable deficits in both alcohol dependents
      and abusers. All deficits were significant when compared with population norms.
      CONCLUSIONS: Findings suggest that prevalence of alcohol abuse, major depression,
      and cognitive impairment is common in head and neck cancer patients
      preoperatively. Early diagnosis and management of these disorders should be
      considered in care of the head and neck cancer patient.

PMID- 17210342
TI  - The effectiveness of salvage surgery after the failure of primary concomitant
      chemoradiation in head and neck cancer.
AB  - OBJECTIVE: To determine survival outcomes and locoregional control rates in
      patients with locoregional head and neck squamous cell cancer (HNSCC) who failed
      primary concomitant chemoradiation (CRT) intended for cure and underwent
      attempted surgical salvage. STUDY DESIGN AND SETTING: Design was a nonrandomized
      retrospective cohort study. Of 204 patients with HNSCC who received primary
      concomitant chemoradiation intended for cure between 1995 and 2004, 38 recurred
      and underwent attempted salvage surgery at a tertiary care academic center.
      RESULTS: Among the 38 patients undergoing surgical salvage, 12- and 24-month
      overall survival rates were 60 percent and 27 percent. Locoregional control at 24
      months was 42 percent. Lower survival was seen with initial N3 disease (P =
      0.0115). Overall surgical morbidity was 24 percent. CONCLUSION/SIGNIFICANCE: The
      results of salvage surgery after failed chemoradiation for HNSCC are poor. Those
      with N3 disease fare least well. Patients should be well informed about the
      realistic chances of cure and potential morbidity of surgery.

PMID- 17210343
TI  - Endoscopic treatment of esthesioneuroblastoma: a minimally invasive approach
      combined with radiation therapy.
AB  - OBJECTIVE: In a retrospective analysis we discuss our experience in the treatment
      of olfactory neuroblastoma (ON), a rare tumor of the sinonasal tract. STUDY
      DESIGN AND SETTING: Nine patients with olfactory neuroblastoma were treated at
      the Bolognini Hospital of Seriate and at the Department of Otolaryngology of "La
      Sapienza" University of Rome combining endoscopic surgery and postoperative
      radiation therapy. All patients were staged according to Kadish criteria. No
      chemotherapy was administered in any cases. Local radiation therapy was started
      postoperatively in all the cases. RESULTS: All patients, over an average follow
      up which ranged from 26 through 60 months, are actually alive with non evidence
      of disease (NED). CONCLUSIONS: Despite the short follow-up in this small series
      of patients, we suggest endoscopic surgery combined with postoperative radiation
      therapy as an alternative to the conventional modalities of treatment for
      esthesioneuroblastoma in selected cases.

PMID- 17210344
TI  - Deterioration in quality of life and depressive symptoms during radiation therapy
      for head and neck cancer.
AB  - OBJECTIVE: The aim of this study was to assess the quality of life and
      psychologic profile during radiation therapy for head and neck cancer. STUDY
      DESIGN AND SETTING: The University of Washington QoL instrument and the Hospital
      Anxiety and Depression Scale were administered to 202 patients at two or three
      time points during radiation therapy. RESULTS: A total of 118 (54.6%) patients
      completed the questionnaires at the beginning and at the end of the study. A mid
      treatment dataset was also available for 67 (31.0%) patients. There was a
      statistically significant deterioration in composite QoL scores (P < 0.000) and a
      statistically significant increase in depression (P < 0.000). There was no
      difference in anxiety levels (P = 0.276). CONCLUSION: Patients undergoing
      radiation are increasingly depressed as treatment progresses, with worsening QoL
      during the treatment. SIGNIFICANCE: This study underlines the need for good
      psychologic support during radiation therapy in head and neck cancer.

PMID- 17210345
TI  - Impact of recurrence interval on survival of oral cavity squamous cell carcinoma
      patients after local relapse.
AB  - OBJECTIVE: The aim of this study was to investigate whether the recurrence
      interval influenced the survival of oral cavity squamous cell carcinoma patients
      after relapse. STUDY DESIGN AND SETTING: Retrospective charts were reviewed at a
      medical center. METHODS: We retrospectively reviewed 1687 chart records of oral
      cancer patients. Statistical methods included descriptive statistics, bivariate
      analyses, Kaplan-Meier survival analyses, and Cox proportional hazard models for
      investigating the relationship between the recurrence interval and survival of
      oral cancer patients after relapse. RESULTS: Local recurrence rate was 31.3
      percent. Kaplan-Meier survival analyses showed the 5-year overall survival after
      recurrence was 31.56 percent. Cox proportional hazard model revealed that those
      with recurrence interval less than 18 months tended to have a higher probability
      of death than those with recurrence interval greater than or equal to 18 months
      (relative risk, 1.743; 95% confidence interval, 1.298-2.358). CONCLUSION: The
      interval from initial treatment to recurrence is an independent prognostic factor
      for oral squamous cell carcinoma patients. Those with a shorter disease-free
      interval tend to have a less favorable outcome.

PMID- 17210346
TI  - Clinical-pathological study of the healing of wounds provoked on the dorso
      lingual mucosa in 186 albino rats.
AB  - OBJECTIVE: To evaluate wound healing of incisions created in the upper
      aerodigestive tract. STUDY DESIGN AND SETTING: In this prospective and blind
      study, 186 adult rats were assigned to six groups to create incisions in the
      tongue. In the first three groups, the wounds were made with a steel scalpel; no
      substance was applied to the wound in the first group, but N-butyl-2
      cyanoacrylate was applied in the second group, and trichloroacetic acid at 50
      percent in the third group. In the fourth, fifth, and sixth groups, the wounds
      were caused by cryosurgery, electrocautery, and CO(2) laser. Hemostasis,
      postoperative oral intake, and wound healing were measured. Statistical analysis
      was performed with analysis of variance. RESULTS: The wounds to which N-butyl-2
      cyanoacrylate was applied showed no hemorrhaging and faster reepithelialization
      and resolution of the inflammatory response. CONCLUSIONS: N-butyl-2-cyanoacrylate
      is a good hemostatic for managing wounds in the oral mucosa provoked by steel
      scalpel.

PMID- 17210347
TI  - Use of a mobile operative unit for in-patient otolaryngology procedures.

PMID- 17210348
TI  - Endoscopic image-guided removal of metallic intravascular foreign body of the
      skull base.

PMID- 17210349
TI  - Nasal pyogenic granuloma.

PMID- 17210350
TI  - Intraoperative identification and management of thyroid storm in children.

PMID- 17210351
TI  - Congenital teratoid cyst of the floor of the mouth.

PMID- 17210352
TI  - Ethmoidal desmoid tumor in a pediatric patient.

PMID- 17210353
TI  - Management of inflammatory pseudotumor of the larynx.

PMID- 17210354
TI  - Angiolipoma of the larynx.

PMID- 17210355
TI  - Nasopharyngeal branchial cleft cyst.

PMID- 17210356
TI  - Coccidioidomycosis presenting as midline neck mass.

PMID- 17210357
TI  - Metastatic acinic cell carcinoma of the parotid gland with ectopic ACTH syndrome.

PMID- 17210358
TI  - Lipoma of the nasal dorsum: an unusual presentation of a common neoplasm.

PMID- 17210359
TI  - An unusual presentation of a cholesterol granuloma in a pneumatized pterygoid
      process of the sphenoid sinus.

PMID- 17210360
TI  - Epidermal cyst of the bony external auditory canal.

PMID- 17210361
TI  - The impact/role of asthma in otolaryngology.

PMID- 17210366
TI  - MAT dilemma.

PMID- 17210367
TI  - Heads up--compliance with public law 106-430.

PMID- 17210368
TI  - Do you do strategic planning?

PMID- 17210370
TI  - The new high. EMS crews confronted with heroin-fentanyl ODs.

PMID- 17210371
TI  - Complex cardioversion.

PMID- 17210373
TI  - Raising the bar code. Technology allows the tracking of patients & crews.

PMID- 17210379
TI  - Plaque excision with the Silverhawk catheter: early results in patients with
      claudication or critical limb ischemia.
AB  - OBJECTIVE: This study was conducted to detail the early experience after
      infrainguinal atherectomy using the Silverhawk plaque excision catheter for the
      treatment of symptomatic peripheral vascular disease. METHODS: A prospective
      database was established in August 2004 in which data for operations, outcomes,
      and follow-up were recorded for patients undergoing percutaneous plaque excision
      for peripheral arterial occlusive disease. Society for Vascular Surgery (SVS)
      ischemia scores and femoropopliteal TransAtlantic Inter-Society Consensus (TASC)
      criteria were assigned. A follow-up protocol included duplex ultrasound
      surveillance at 1, 3, and 6 months and then yearly thereafter. Standard
      statistical analyses were performed. RESULTS: During a 17-month period, 66 limbs
      of 60 patients (37 men [61.7%]) underwent 70 plaque excisions (four repeat
      procedures). Indications included tissue loss based on SVS ischemia at grades 5
      and 6 (25/70), rest pain at grade 4 (22/70), and claudication at grades 2 to 3
      (23/70). The mean lesion length was 8.8 +/- 0.7 cm. The technical success rate
      was 87.1% (61/70). Adjunctive treatment was required in 17 procedures (24.3%),
      consisting of 14 balloon angioplasties and three stents. Femoropopliteal TASC
      criteria included 5 TASC A lesions, 14 TASC B lesions, 32 TASC C lesions, and 19
      TASC D lesions. Although 17 plaque excisions included a tibial vessel, no patient
      underwent isolated tibial atherectomy. The mean increase in ankle-brachial index
      was 0.27 +/- 0.04 and in toe pressure, 20.3 +/- 6.9 mm Hg. Mean duplex ultrasound
      follow-up was 5.2 months (range, 1 to 17 months). One-year primary, primary
      assisted, and secondary patency was 61.7%, 64.1%, and 76.4%, respectively.
      Restenosis or occlusion developed in 12 patients (16.7%) and was detected at a
      mean of 2.8 +/- 0.7 months. Restenosis or occlusion was significantly more common
      (P < .05) in patients with TASC C and D lesions compared with patients with TASC
      A and B lesions. Six (8.3%) of 12 patients underwent reintervention on the basis
      of duplex ultrasound surveillance results. Four (33.3%) of 12 patients
      experienced reocclusion during the same hospitalization, and amputation and open
      revascularization were required in two patients each. CONCLUSIONS: Percutaneous
      plaque excision is a viable treatment option for lower extremity
      revascularization. Outcomes are related to ischemia and lesion severity. Patency
      and limb salvage rates are equivalent to other endovascular modalities.

PMID- 17210380
TI  - Endovascular treatment of long lesions of the superficial femoral artery: results
      from a multicenter registry of a spiral, covered polytetrafluoroethylene stent.
AB  - OBJECTIVE: Information on outcome of patients with long superficial femoral
      artery (SFA) obstruction undergoing endovascular treatment is scarce. The present
      study reports results from a prospective multicenter registry designed to
      evaluate the safety, effectiveness, and patency of the aSpire self-expanding
      polytetrafluoroethylene covered stent (Vascular Architects Inc, San Jose, Calif)
      in patients with femoropopliteal occlusive disease. METHOD: The aSpire Registry
      included 150 patients (166 limbs) enrolled in 16 centers during a 28-month period
      (2003 to 2005) for medium/long (>3 cm) occlusion (n = 115) or stenosis (n = 51)
      of the SFA (n = 51) or of the proximal popliteal (n = 115) arteries. Procedures
      were performed for intermittent claudication in 92, for rest pain in 33, and for
      limb savage in 41. The mean length of arterial segment covered was 107.35 +/-
      73.7 mm. Indications for treatment included 44 type B1, 57 type B2, 47 type C1,
      and 18 type D lesions according to TransAtlantic Inter-Society Consensus
      classification. Clinical and ultrasound evaluation was performed at discharge and
      at 1, 6, 12 months, and yearly thereafter. Mean follow-up was 13 months (range, 1
      to 36). Primary end points were immediate technical success (vessel
      recanalization with residual stenosis < or =30%) and stent patency. RESULTS:
      Initial technical success was obtained in 162 (97.6%) of 166 procedures. More
      than one stent was applied in 48 procedures, for a total of 214 stents. No
      periprocedural deaths occurred. Procedure-related complications occurred in 22 of
      166 procedures, including 6 peripheral embolizations, 7 thromboses, 2 hemorrhages
      requiring revision, 1 vessel rupture, and 6 vessel dissections. Life-table
      estimates of primary patency at 12, 24, and 36 months were 64%, 59%, and 59%,
      respectively. Thirty-two reinterventions were performed during follow-up,
      resulting in secondary patency rates at 12, 24, and 36 months of 74.2%, 67%, and
      67%, respectively. Amputation was required in six of 41 patients treated for limb
      salvage. At multivariate analysis, critical limb ischemia was the only
      significant predictor of late failure. CONCLUSION: Endovascular treatment of SFA
      occlusive lesions provides interesting results. Length of lesion and clinical
      symptoms influence negatively the patency. The aSpire covered stent showed good
      mid-term results, but a number of reinterventions were necessary to obtain an
      optimal secondary patency. Risk of patency failure was related to critical limb
      ischemia as an indication for the procedure. Technologic and pharmacologic
      improvement and longer follow-up are needed to define the indications for the
      aSpire stent.

PMID- 17210381
TI  - The course of vascular risk factors and the occurrence of vascular events in
      patients with symptomatic peripheral arterial disease.
AB  - BACKGROUND: Previous studies have documented an undertreatment of vascular risk
      factors, and patients with symptomatic peripheral arterial disease (PAD) are at
      increased risk of recurrent vascular events. We examined which baseline variables
      are related to future vascular events, investigated the course of vascular risk
      factors, and compared the number of vascular risk factors at baseline and at
      follow-up to determine whether risk factor management could be further improved.
      METHODS: This study involved 461 patients with Fontaine classification II to IV
      who were enrolled in the SMART study (Second Manifestations of ARTerial disease)
      from September 1996 to December 2000. Patients underwent a standardized screening
      program for risk factors and were invited for a follow-up measurement during
      September 2003 to March 2005, after a mean follow-up of 5.5 years (SD, 1.3
      years). In the interim period between baseline and follow-up measurement,
      patients received usual care. During follow-up, vascular events (mortality,
      ischemic stroke, and myocardial infarction) and PAD-related events (vascular
      surgery, interventions, and amputations) were documented in detail. RESULTS: In
      2739 person-years of follow-up, 91 vascular events occurred, resulting in a 29.1%
      (95% confidence interval [CI], 22.8%-35.4%) cumulative incidence proportion of
      recurrent vascular events. Older age, increased homocysteine levels, impaired
      renal function, and a history of coronary heart disease at baseline were related
      to an increased risk of new vascular events. Of the 461 patients, 108 patients
      died, 20 patients were lost to follow-up, and 333 patients were eligible for
      follow-up measurement, in which 221 (66%) patients wished to participate. In 8 of
      the 221 patients, a nonfatal vascular event occurred during follow-up. The
      prevalence of hypertension increased from 51% to 70% (95% CI, 10%-28%), the
      prevalence of obesity increased from 54% to 67% (95% CI, 3%-21%), and the
      prevalence of diabetes mellitus increased from 8% to 16% (95% CI, 2%-14%). At
      follow-up, fewer patients were current smokers (59% to 37%; 95% CI, -13% to 
      31%), and fewer patients had increased lipid levels (96% to 73%; 95% CI, -29% to 
      16%). Medication use increased in all drug categories during follow-up.
      CONCLUSIONS: Age, increased homocysteine levels, impaired renal function, and a
      history of coronary heart disease were independent risk factors for vascular
      events in patients with symptomatic PAD. The prevalence of most risk factors,
      except for smoking and hyperlipidemia, increased over a 5.5-year period even
      though medication use increased over the same period.

PMID- 17210382
TI  - The adverse effects of race, insurance status, and low income on the rate of
      amputation in patients presenting with lower extremity ischemia.
AB  - OBJECTIVES: A consequence of delay in the diagnosis of peripheral vascular
      disease limb loss. This study was undertaken to determine the correlation of low
      socioeconomic status and race on the severity of ischemic presentation and the
      subsequent amputation rate. METHODS: Data from the Nationwide Inpatient Sample
      (NIS) from 1998 to 2002 on patients from urban hospitals with the diagnosis of
      lower extremity ischemia were evaluated. The population was divided into two
      groups: the amputation group (AMP) and lower extremity revascularization group
      (LER). Comorbidities, age, gender, race, ischemic gangrene at presentation,
      insurance status (no/noncommercial or commercial), and income status at admission
      were determined. These variables were compared using multivariate logistic
      regression analyses of the data for risk adjustment. RESULTS: Of 691,833 patients
      presenting with lower extremity ischemia, 363,193 underwent revascularization
      (66.3%) or amputation (33.7%). Univariate analysis correlated a statistically
      significant (P < .0001) higher rate of amputation and multivariate analysis
      associated significantly higher odds of amputation with the following variables:
      nonwhites (1.91, 95% confidence interval [CI], 1.65, 2.20), low-income bracket
      (1.41, 95% CI, 1.18, 1.60), and Medicare & Medicaid (1.81, 95% CI, 1.66, 1.97).
      Adjusting for other variables of statistical significance, multivariate
      regression analysis showed a statistically significant risk for amputation based
      on the nonteaching status of the institution (odds ratio [OR], 1.17, 95% CI,
      1.08, 1.30). CONCLUSIONS: Primary amputation was performed with a higher
      frequency on patients with lower extremity ischemia who were nonwhite, low
      income, and without commercial insurance. The observed advanced ischemia among
      these economically disadvantaged patients suggests a delayed diagnosis of
      peripheral vascular disease, probably due to lack of access to adequate primary
      care or vascular surgery providers, or both. Better education of the general
      population and primary care providers to the symptoms and consequences of PVD may
      reduce the amputation rate in this group.

PMID- 17210383
TI  - The effect of supervised exercise and cilostazol on coagulation and fibrinolysis
      in intermittent claudication: a randomized controlled trial.
AB  - BACKGROUND: The prothrombotic, hypofibrinolytic state that develops in patients
      with intermittent claudication (IC) upon walking due to ischemia-reperfusion
      injury (IRI) of the leg muscles may contribute to the high incidence of life- and
      limb-threatening thrombotic events observed in this patient group. Treatments,
      such as angioplasty, that obtund the IRI also ameliorate the procoagulant
      diathesis. The effect on this diathesis of supervised exercise and cilostazol,
      both of which provide symptomatic benefit in IC, but without significantly
      obtunding IRI, is unknown. METHODS: Thirty-four patients (27 men and 7 women;
      median age, 67 years; range, 63-72 years) were randomized to receive best medical
      therapy (BMT) plus supervised exercise (n = 9), BMT plus cilostazol (n = 9), BMT
      plus supervised exercise plus cilostazol (n = 7), or BMT alone (n = 9) in a 2 x 2
      factorial design. Thrombin-antithrombin complex and prothrombin fragments 1 and
      2, both markers of thrombin generation; plasminogen activator inhibitor antigen
      and tissue plasminogen activator antigen, both markers of fibrinolysis; ankle
      brachial pressure index (ABPI); and initial and absolute claudication distance
      (ACD) were measured at baseline and then 3 and 6 months after randomization.
      RESULTS: At 6 months, when compared with receiving BMT only, supervised exercise
      and cilostazol resulted in improvements in ABPI of 18% and 13% and in ACD of 40%
      and 64%, respectively. The effects on ABPI and ACD of combining supervised
      exercise and cilostazol were additive. Supervised exercise, cilostazol, and
      supervised exercise combined with cilostazol had no significant effect on any of
      the four hemostatic markers. CONCLUSIONS: Treatment of IC by supervised exercise
      or cilostazol results in significant improvements in ABPI and ACD but has no
      demonstrable effect on the prothrombotic diathesis. This suggests that supervised
      exercise and cilostazol, unlike angioplasty, are unlikely to have a long-term
      beneficial effect on the thrombotic risks faced by these patients.

PMID- 17210385
TI  - Magnetic resonance angiography and neuromonitoring to assess spinal cord blood
      supply in thoracic and thoracoabdominal aortic aneurysm surgery.
AB  - OBJECTIVE: Preoperative knowledge of the blood-supplying trajectory to the spinal
      cord is of interest, because spinal cord ischemia may occur during thoracic
      aortic aneurysm (TAA) and thoracoabdominal aortic aneurysm (TAAA) repair and
      possibly leads to paraplegia. The Adamkiewicz artery (AKA) is considered to be
      the most important blood supplier of the thoracolumbar spinal cord and has
      therefore been the focus in preoperative diagnostic imaging. However, in TAA(A)
      patients, the blood supply to the spinal cord may strongly depend on
      (intersegmental) collateral circulation, because many segmental arteries are
      occluded as a result of atherosclerosis. Therefore, the importance of preserving
      the segmental artery supplying the AKA (SA-AKA) is debated. Here it was
      investigated whether (1) the AKA and its segmental supplier can be imaged by
      using magnetic resonance (MR) angiography and (2) aortic cross-clamping of the SA
      AKA influences intraoperative spinal cord function, monitored by motor evoked
      potentials (MEPs). METHODS: Preoperative MR angiography was performed to localize
      the SA-AKA and the AKA in 60 patients (19 TAA, 7 TAAA I, 18 TAAA II, 9 TAAA III,
      and 7 TAAA IV). Spinal cord function was monitored during surgery by using MEPs.
      When MEPs indicated critical ischemia, the SA-AKA was selectively reattached. To
      test whether aortic cross-clamping of the SA-AKA was associated with MEP decline,
      the Fisher statistical exactness test was applied. RESULTS: The AKA and SA-AKA
      could be localized in all 60 (100%) patients between vertebral levels T8 and L2
      (72% left sided). In 44 (73%) patients, the SA-AKA was cross-clamped, which led
      in 32% (14/44) of cases to MEP decline. Reattachment of the preoperatively
      localized SA-AKA re-established MEPs and, thus, spinal cord function in 12 of 14
      cases. When the SA-AKA was outside the area cross-clamped, the MEPs always
      remained stable. A significant association (P < .01) was found between the
      location of the SA-AKA relative to the aortic cross-clamps and the MEPs.
      CONCLUSIONS: The AKA can be localized before surgery in 100% of TAA(A) patients
      by using MR angiography. Location of the SA-AKA outside the cross-clamped aortic
      area is attended with stable MEPs. Interestingly, it was found that in most
      patients in whom the SA-AKA was cross-clamped, MEPs were not affected, thus
      indicating sufficient collateral blood supply to maintain spinal cord integrity.
      Nevertheless, preoperative knowledge of SA-AKA location is of importance, because
      in 32% of patients, spinal cord function was dependent on this supplier.
      Revascularization of the SA-AKA can thereby reverse spinal cord dysfunction.

PMID- 17210387
TI  - The influence of aortic cuffs and iliac limb extensions on the outcome of
      endovascular abdominal aortic aneurysm repair.
AB  - BACKGROUND: In a proportion of patients with an endovascular abdominal aortic
      aneurysm repair (EVAR), aortic cuffs or iliac graft limb extensions are required
      to enhance sealing or to fix the position of the device. This requirement arises
      when these goals are not primarily obtained with the basic stent-graft
      configuration. The aim of this study was to assess the influence of the use of
      endograft extensions during the primary EVAR procedure on the short- and long
      term outcome. METHODS: The study was based on the data of the EUROSTAR registry.
      Patient and anatomic characteristics, data regarding the procedure, postoperative
      complications, and the mortality of patients undergoing EVAR were retrieved from
      the database. Patients were divided into three groups: (1) no extensions, (2)
      proximal aortic cuffs, and (3) iliac limb extensions. Logistic regression and Cox
      proportional hazards models were used to compare significant influences of the
      use of cuffs or extensions on different outcomes relative to control patients,
      adjusted for patient and anatomic factors. RESULTS: The overall cohort comprised
      6668 patients: 4932 (74.0%) without extensions, 259 (3.9%) with an aortic cuff,
      and 1477 (22.2%) with an iliac endograft extension. Both the 30-day (2.3%-3.9%)
      and the all-cause mortality rates (23%-27% at 4 years) were similar in the three
      study groups. The use of proximal cuffs or iliac extensions did not have an
      effect on the incidence of endoleaks of any type (24%-32% at 4 years). The
      incidences of device kinking (P = .0344) and secondary transfemoral interventions
      (P = .0053) during follow-up were increased in patients in whom iliac limb
      extensions were used. In patients with aortic cuffs, no significant associations
      with altered outcome were observed. CONCLUSIONS: The use of iliac graft limb
      extensions at EVAR was associated with a higher incidence of kinking and
      secondary transfemoral interventions, whereas proximal aortic cuffs did not
      influence outcome.

PMID- 17210388
TI  - Perioperative differences between endovascular repair of thoracic and abdominal
      aortic diseases.
AB  - BACKGROUND: With the US Food and Drug Administration approval of the TAG thoracic
      device, more thoracic pathologies are being treated using endovascular
      techniques. Although endovascular abdominal and thoracic aortic repairs have some
      apparent similarities, there are substantive anatomic, pathologic, and technical
      differences that could impact perioperative outcomes. The purpose of this study
      is to identify these differences. METHODS: During a 5-year period, 121
      endovascular thoracic aortic repairs (TEVAR) and 450 abdominal aortic repairs
      (EVAR) were performed at a single institution. Preoperative, intraoperative, and
      early postoperative data were prospectively collected and retrospectively
      reviewed. Aggregate outcome measures were compared between the two cohorts, with
      statistical significance achieved at P < .05. RESULTS: The mean age of patients
      undergoing EVAR was 72.8 +/- 8.3 compared with 68.3 +/- 13.9 for TEVAR (P = .02).
      More women underwent TEVAR (30.6% vs 11.1%, P < .001). Aneurysms undergoing TEVAR
      were larger than those for EVAR (62.0 mm vs 58.3 mm, P = .01). Intraoperatively,
      EVAR required 26.2 minutes of fluoroscopy compared with 22.1 minutes for TEVAR (P
      < .001). The amount of contrast used was higher in TEVAR (133.6 mL vs 93.6 mL, P
      < .001). The mean procedure times were 164 minutes for EVAR and 115 minutes for
      TEVAR (P < .001). Iliac conduits were required in 46 patients (10.2%) undergoing
      EVAR, and in 24 (19.8%) undergoing TEVAR (P = .007). The 30-day or in-hospital
      mortality was 2.0% for EVAR and 5.0% for TEVAR (P = NS). The median length of
      stay was longer for TEVAR (3 days vs 2 days, P =.034). There were 54
      postoperative complications in 36 TEVAR patients (29.8%), including 13 neurologic
      (10.7%), 8 renal (6.6%), 7 pulmonary (5.8%), 6 ischemic (5.0), and 5 (4.1%)
      hemorrhagic events. Among the EVAR group, 136 (30.2%) patients had postoperative
      complications, which included 45 ischemic (10.0%), 34 wound (7.6%), 22 renal
      (4.9%), 12 cardiac (2.7%), 8 pulmonary (1.8%), 5 gastrointestinal (1.1%), and 4
      neurologic (0.9%) events. CONCLUSIONS: A relatively higher proportion of women
      underwent TEVAR than EVAR, and this was reflected in the greater need for iliac
      conduits to accommodate the larger delivery catheters of the thoracic devices.
      Intraoperative imaging techniques were also different, and TEVAR required higher
      contrast volumes despite shorter overall procedure times. The incidence of
      strokes and spinal cord ischemia was also higher during TEVAR. Despite apparent
      similarities of devices and techniques, EVAR and TEVAR are fundamentally
      different procedures with different perioperative outcomes.

PMID- 17210389
TI  - Coverage of the left subclavian artery during thoracic endovascular aortic
      repair.
AB  - BACKGROUND: Thoracic aortic stent grafts require proximal and distal landing
      zones of adequate length to effectively exclude thoracic aortic lesions. The
      origins of the left subclavian artery and other aortic arch branch vessels often
      impose limitations on the proximal landing zone, thereby disallowing endovascular
      repair of more proximal thoracic lesions. METHODS: Between October 2000 and
      November 2005, 112 patients received stent grafts to treat lesions involving the
      thoracic aorta. The proximal aspect of the stent graft partially or totally
      occluded the origin of at least one great vessel in 28 patients (25%). The
      proximal attachment site was in zone 0 in one patient (3.6%), zone 1 in three
      patients (10.7%), and zone 2 in 24 patients (85.7%). Patients with proximal
      implantation in zones 0 or 1 underwent debranching procedures of the supra-aortic
      vessels before stent graft repair. In one patient who underwent zone 1
      deployment, the left subclavian artery was revascularized before stent graft
      deployment. Among patients who underwent zone 2 deployment with partial or
      complete occlusion of the left subclavian artery, none underwent prior
      revascularization. Patients were assessed postoperatively and at follow-up for
      development of neurologic symptoms as well as symptoms of left upper extremity
      claudication or ischemia. RESULTS: Mean follow-up was 7.3 months. Among the 24
      patients with zone 2 implantation, 10 (42%) had partial left subclavian artery
      coverage at the time of their primary procedure. A total of 19 patients
      experienced complete cessation of antegrade flow through the origin of the left
      subclavian artery without revascularization at the time of the initial endograft
      repair as a result of a secondary procedure or as a consequence of left
      subclavian artery thrombosis. Left upper extremity symptoms developed in three
      (15.8%) patients that did not warrant intervention, and rest pain developed in
      one (5.3%), which was treated with the deployment of a left subclavian artery
      stent. Two primary (type IA and type III) endoleaks (7.1%) and one secondary
      endoleak (type IA) (3.6%) were observed in patients who underwent zone 2
      deployment. Three cerebrovascular accidents were observed. Thoracic aortic
      lesions were successfully excluded in all patients who underwent supra-aortic
      debranching procedures. CONCLUSION: Intentional coverage of the origin of the
      left subclavian artery to obtain an adequate proximal landing zone during
      endovascular repair of thoracic aortic lesions is well tolerated and may be
      managed expectantly, with some exceptions.

PMID- 17210391
TI  - Surveillance of small aortic aneurysms does not alter anatomic suitability for
      endovascular repair.
AB  - OBJECTIVE: Small abdominal aortic aneurysms (AAAs; 4-5.4 cm) are more likely to
      be suitable for endovascular aneurysm repair (EVAR) than large aortic aneurysms
      (>5.5 cm). The purpose of this study was to determine whether small AAA growth is
      associated with the development of morphologic characteristics that decrease
      eligibility for EVAR. METHODS: We studied 54 patients who underwent 2 or more
      computed tomography scans with 3-dimensional reconstruction during surveillance
      of small AAAs. Morphologic aortic aneurysm features and changes were measured
      according to Society for Vascular Surgery reporting standards. Suitability for
      EVAR was determined by neck anatomy (diameter, length, and angulations), iliac
      artery morphology, and total aortic aneurysm angulation and tortuosity. RESULTS:
      The median age of the study cohort was 73 years (interquartile range [IQR], 65-77
      years). The median follow-up period was 24 months (IQR, 15-36 months). The median
      small AAA diameter increased from 44.5 mm (IQR, 41-48 mm) to 48.9 mm (IQR, 45.7
      52.0 mm). The median aortic neck diameter increased from 23.0 to 24.0 mm (P =
      .002), whereas median neck length decreased from 26.5 to 20.0 mm (P = .001).
      Aortic aneurysm median tortuosity index increased from 1.09 to 1.11 (P = .05). No
      significant changes in iliac artery morphology occurred. Overall, the anatomic
      suitability for endovascular repair did not significantly change during the study
      period (74% vs 69%; McNemar test; P = .25). CONCLUSIONS: Changes in aortic
      morphology are frequently associated with small AAA growth at mid-term follow-up,
      but such changes are minor and do not affect overall anatomic suitability for
      EVAR. These data reveal that continued surveillance of small AAAs does not
      threaten the window of opportunity for EVAR.

PMID- 17210392
TI  - The management of renal artery atherosclerosis for renal salvage: does stenting
      help?
AB  - OBJECTIVE: The use of endovascular techniques to treat renal artery stenosis
      (RAS) has increased in recent years but remains controversial. The purpose of
      this study was to review the outcomes and durability of percutaneous transluminal
      angioplasty and stenting (PTA/S) for patients with RAS and decreasing renal
      function. METHODS: Between 1999 and 2004, 125 consecutive patients underwent
      angiography and intervention for renal salvage and formed the basis of this
      study. Inclusion criteria for this study included serum creatinine greater than
      1.5 mg/dL, ischemic nephropathy, and high-grade RAS perfusing a single
      functioning kidney. Patients undergoing PTA/S for renovascular hypertension or
      fibromuscular dysplasia or in conjunction with endovascular stent grafting for
      aneurysm repair were excluded. The original angiographic imaging was evaluated
      for lesion grade and parenchymal kidney size. All medical records and noninvasive
      testing were reviewed. Preoperative and postoperative patient data were
      standardized and analyzed by using chi(2) tests for nominal values and t tests
      for continuous variables. The Modification of Diet in Renal Disease equation was
      used to estimate glomerular filtration rate (GFR), and univariate analysis was
      performed. RESULTS: Preoperative variables included the presence of coronary
      artery disease (93%), diabetes (44%), tobacco use (48%), and hypercholesterolemia
      (70%). RAS was suspected on the basis of preoperative duplex imaging or magnetic
      resonance angiography. Aortography and PTA/S were performed in 125 patients (mean
      age, 71 years; 59% male) with a mean baseline creatinine level of 2.2 mg/dL.
      There were two mortalities (1.6%) in the 30-day postoperative period, but there
      was no case of acute renal loss. Blood pressure decreased after PTA/S (151/79 mm
      Hg before vs 139/72 mm Hg after 1 month; P < .03). For all patients, the
      estimated GFR went from 33 +/- 12 mL . min(-1) . 1.73 m(-2) (mean +/- SD) to 37
      +/- 19 mL . min(-1) . 1.73 m(-2) at 6 months (P = .10). Sixty-seven percent of
      treated patients had improvement (>10% increase in GFR) or stabilization of renal
      function. A rapid decline in GFR before intervention was correlated with
      improvement after PTA/S. Responders after PTA/S had a 27% decrease in GFR before
      intervention (44 +/- 13 mL . min(-1) . 1.73 m(-2) to 32 +/- 13 mL . min(-1) .
      1.73 m(-2); P < .001) with a negative to positive slope change in GFR values. Ten
      patients underwent reintervention for in-stent restenosis. Cases without
      improvement in GFR after PTA/S were associated with eventual dialysis need (P =
      .01; mean follow-up, 19 months). Survival at 3 years was 76%, and dialysis-free
      survival was 63% as estimated by Kaplan-Meier analyses. CONCLUSIONS: Renal artery
      stenoses causing renal dysfunction can be safely treated via endovascular means.
      Rapidly decreasing renal function is associated with the response to renal artery
      angioplasty/stenting and helps identify patients for renal salvage.

PMID- 17210394
TI  - Radiation arteritis: a contraindication to carotid stenting?
AB  - BACKGROUND: Carotid artery stenting (CAS) for high-risk anatomic lesions is
      accepted practice. Neck irradiation and radiotherapy-induced arteritis are common
      indications. The clinical outcomes of CAS for radiation arteritis have been
      poorly defined. METHODS: A prospective database of patients undergoing CAS at a
      tertiary referral academic medical center was maintained from 1999 to 2006.
      Patients undergoing primary carotid artery stenting for significant
      atherosclerotic (ASOD) and radiotherapy (XRT)-induced occlusive disease were
      analyzed. Life-table analyses were performed to assess time-dependent outcomes.
      Cox proportional hazard analysis or Fisher's exact test was performed to identify
      factors associated with outcomes. Data are presented as the mean +/- SEM unless
      otherwise indicated. RESULTS: During the study period, 150 patients underwent
      primary CAS, 75% with embolic protection. Fifty-eight percent were symptomatic.
      One hundred twenty-seven (85%) were treated for ASOD, and 23 (15%) had XRT. The
      30-day all-cause mortality rate was 1% for ASOD and 0% for XRT (P = NS); overall
      survival at 3 years was equivalent. There was no significant difference in major
      adverse event rates as defined by the Stenting and Angioplasty with Protection in
      Patients at High Risk for Endarterectomy (SAPPHIRE) trial between the groups. The
      3-year neurologic event-free rate was 85% for ASOD and 87% for XRT (P = NS). Late
      asymptomatic occlusions were seen only in XRT patients. The 3-year freedom from
      restenosis rate was significantly worse for the XRT group, at 20%, vs 74% for the
      ASOD group (P < .05). Likewise, the 3-year patency rate was also worse for the
      XRT group, at 91%, vs 100% for ASOD by Kaplan-Meier analysis (P < .05). No factor
      was predictive of occlusion or stenosis by Cox proportional hazards analysis.
      CONCLUSION: CAS for radiation arteritis has poor long-term anatomic outcome and
      can present with late asymptomatic occlusions. These findings suggest that these
      patients require closer postoperative surveillance and raise the question of
      whether CAS is appropriate for carotid occlusive lesions caused by radiation
      arteritis.

PMID- 17210395
TI  - Carotid angioplasty and stenting for postendarterectomy stenosis: long-term
      follow-up.
AB  - BACKGROUND: Carotid angioplasty and stenting (CAS) for recurrent stenosis after
      carotid endarterectomy (CEA) has been proposed as an alternative to redo CEA.
      Although early results are encouraging, the extended durability remains unknown.
      We present the long-term surveillance results of CAS for post-CEA restenosis.
      METHODS: Between 1998 and 2004, 57 CAS procedures were performed in 55 patients
      (36 men) with a mean age of 70 years. The mean interval between CEA and CAS was
      83 months (range, 6 to 245). Nine patients (16%) were symptomatic. RESULTS: CAS
      was performed successfully in all patients. No deaths or strokes occurred. A
      periprocedural transient ischemic attack (TIA) occurred in two patients. During a
      mean follow-up of 36 months (range, 12 to 72 months), two patients exhibited
      ipsilateral cerebral symptoms (1 TIA, 1 minor stroke). In 11 patients (19%), in
      stent restenosis (> or =50%) was detected post-CAS at month 3 (n = 3), 12 (n =
      3), 24 (n = 2), 36 (n = 1), 48 (n = 1), and 60 (n = 1). The cumulative rates of
      in-stent restenosis-free survival at 1, 2, 3, and 4 years were 93%, 85%, 82%, and
      76%, respectively. Redo procedures were performed in six patients, three each
      received repeat angioplasty and repeat CEA with stent removal. The cumulative
      rates of freedom from reintervention at 1, 2, 3, and 4 years were 96%, 94%, 90%,
      and 84%, respectively. CONCLUSION: Carotid angioplasty and stenting for recurrent
      stenosis after CEA can be performed with a low incidence of periprocedural
      complications with durable protection from stroke. The rate of in-stent recurrent
      stenosis is high, however, and does not only occur early after CAS but is an
      ongoing process.

PMID- 17210396
TI  - Factors associated with a provider's recommendation of carotid endarterectomy:
      implications for understanding disparities in the use of invasive procedures.
AB  - OBJECTIVE: This study assessed the relative importance of clinical and
      nonclinical factors in a provider's decision to recommend carotid endarterectomy
      (CEA) for a patient, with emphasis on the role of the patient's race in the
      provider's assessment of the risks and benefits of the procedure. METHODS: The
      study was a secondary analysis of data on the use of CEA conducted in a patient
      sample of 355 white and black patients who were referred for evaluation for CEA
      and were adjudicated preoperatively as appropriate candidates for the procedure
      by objective criteria. The patients were from five VA medical centers nationally.
      The primary outcome was the provider's recommendation that the patient receive
      CEA. Patient factors included age, race, the degree of carotid artery stenosis,
      clinical status, trust in the provider, and aversion to surgery. Provider factors
      were assessment of the patient's risks and benefits from CEA, including perceived
      efficacy of the surgery, perceived risk of stroke < or =1 year without the
      surgery, and perceived risk of stroke < or =30 days from the surgery. RESULTS:
      The primary factor associated with a provider's decision to recommend CEA was his
      or her assessment of the patient's risk of stroke without the surgery. The
      patient's race was not associated with the provider's assessments of the
      patient's risks or benefits from CEA. CONCLUSION: A major determinant of a
      provider's recommendation for a patient to receive CEA endarterectomy is the
      assessment of the patient's likely future risk of stroke, regardless of the
      patient's race.

PMID- 17210397
TI  - A randomized trial of T3-T4 versus T4 sympathectomy for isolated axillary
      hyperhidrosis.
AB  - INTRODUCTION: Video-assisted thoracic sympathectomy (VATS) is one minimally
      invasive definitive treatment for axillary hyperhidrosis. Different techniques
      exist for controlling axillary sudoresis, but they are temporary and have high
      cost. This study was conducted to compare the initial results from sympathectomy
      using two distinct levels for treating axillary sudoresis: T3-T4 vs T4. METHODS:
      Sixty-two patients with axillary hyperhidrosis were prospectively randomized for
      denervation of T3-T4 or T4 alone. All patients were examined preoperatively and
      were followed-up at 1 and 6 months postoperatively. Evaluated were the axillary
      hyperhidrosis treatment, the presence, location, and severity of compensatory
      hyperhidrosis, and the quality of life. RESULTS: All the patients said that their
      axillary hyperhidrosis was successfully treated by the surgery after 6 months.
      There was no treatment failure. Compensatory hyperhidrosis was present in 29
      patients (90.6%) of the T3-T4 group and in 17 T4 patients (56.7%) after 1 month.
      After 6 months, all the T3-T4 patients presented some degree of compensatory
      hyperhidrosis vs 13 T4 patients (43.3%). The severity of the compensatory
      hyperhidrosis was also lower in the T4 patients (P < . 01). The quality of life
      was poor in both groups before the surgery, and was equally improved in both
      groups after 1 and 6 months of follow-up. There were no deaths or significant
      postoperative complications nor a need for conversion to thoracotomy. CONCLUSION:
      Both techniques are effective for treating axillary hyperhidrosis, but the T4
      group presented milder compensatory hyperhidrosis and had a greater satisfaction
      rate.

PMID- 17210398
TI  - A factorial, randomized trial of pentoxifylline or placebo, four-layer or single
      layer compression, and knitted viscose or hydrocolloid dressings for venous
      ulcers.
AB  - OBJECTIVES: We evaluated the effectiveness of pentoxifylline, knitted viscose or
      hydrocolloid dressings, and single-layer or four-layer bandaging for venous
      ulceration. METHOD: A factorial randomized controlled trial with 24-week follow
      up was conducted in leg ulcer clinics in Scotland with blinded allocation to
      pentoxifylline (1200 mg) or placebo, knitted viscose or hydrocolloid dressings,
      and single-layer or four-layer bandages. The study enrolled 245 adults with
      venous ulcers. The main outcome measure was time to complete healing. Secondary
      outcomes included proportions healed, withdrawals, and adverse events. Analysis
      was by intention to treat. RESULTS: There was no evidence of interaction between
      the drug, bandages, and dressings. Pentoxifylline was associated with
      nonsignificant increased ulcer healing (62% vs 53%; P = .21). Four-layer bandages
      were associated with significantly higher healing rates (67% vs 49%; P = .009).
      There was no difference in healing between knitted viscose and hydrocolloid
      dressings (58% and 57%; P = .88). Cox regression models increased the
      significance of the pentoxifylline effect (relative risk of healing, 1.4; 95%
      confidence interval, 1.0 to 2.0). CONCLUSIONS: Pentoxifylline increased the
      proportion healing compared with placebo to the same extent as shown in recent
      systematic reviews, although this finding was only statistically significant when
      a secondary adjusted analysis was conducted. Four-layer bandaging produced higher
      healing rates than single-layer bandaging. There was no difference in time to
      healing between knitted viscose and hydrocolloid dressings.

PMID- 17210399
TI  - Results of the national pilot screening program for venous disease by the
      American Venous Forum.
AB  - OBJECTIVE: This report describes the pilot of a free comprehensive national
      screening program for venous disease. METHODS: The screening process consisted of
      a venous thromboembolism (VTE) risk assessment, abbreviated duplex examination
      for venous obstruction and reflux, inspection for signs of chronic venous
      insufficiency (CVI), and an exit interview. Physicians coordinating the
      screenings were members of the American Venous Forum. RESULTS: Seventeen
      institutions screened 476 people (mean, 28 per site; range, 6 to 71). Mean age
      was 60 years (range, 40 to 91 years), with 78% women and 68% with a body mass
      index of > or =25. If placed in a situation conducive for VTE, 22 participants
      (5%) were low risk, 87 (18%) were moderate risk, 186 (39%) were high risk, and
      179 (38%) were at very high risk. In 26 people (6%), one or more segments had
      venous obstruction, and 190 (40%) had one or more segments of venous reflux in
      the lower extremities. Varicose veins were present in 32%, edema without skin
      changes in 11%, skin changes attributable to venous disease in 8%, and healed or
      active venous stasis ulcer in 1.3% (CEAP classification 2, 3, 4, 5, and 6,
      respectively). Increasing age and increasing deep venous thrombosis risk score
      significantly correlated with increasing clinical classification, r = 0.09, P =
      .04, and r = 0.16, P = .0004, respectively. Those participants with reflux in one
      or more segments were significantly more likely to have a higher clinical
      classification compared with those with no reflux (P = .0001). CONCLUSION: The
      first comprehensive national screening for venous disease was performed.
      Participants were informed of their risk for VTE if placed in a situation
      conducive to VTE, screened for evidence of obstruction, reflux, and CVI, and
      empowered to share their results with their primary care provider.

PMID- 17210400
TI  - Training with simulation improves residents' endovascular procedure skills.
AB  - BACKGROUND: Endovascular procedure simulators are now commercially available and
      in use for physician training. The purpose of this study was to evaluate the role
      of simulation-based training in vascular surgery residencies. METHODS: Residents
      from vascular surgery programs in a five-state area were invited to participate
      in a series of 2-day endovascular training programs that used a high-fidelity
      endovascular procedure simulator (SimSuite; Medical Simulation Corporation,
      Denver, Colo), didactic instruction, computer-based training, and tabletop
      procedure demonstrations. The curriculum covered arteriography and intervention
      for treatment of aortoiliac, renal, and carotid artery disease. Nine residents
      participated, with one to three per training session. Each completed an average
      of 9.5 simulated endovascular cases. Performance on a standardized TransAtlantic
      Inter-Society Consensus B iliac angioplasty/stenting case was used to assess
      endovascular skills and knowledge at the beginning of the training program, and
      this was repeated at the completion of the training. Performance metrics were
      measured by the simulator, faculty observed trainees' performance of simulated
      cases, and trainees provided their evaluations of the usefulness of the
      simulation experiences. RESULTS: Endovascular procedural skills on the
      standardized iliac intervention case improved after completion of the training
      program. Compared with performance early on day 1, performance improved (P < or =
      .05; paired t test): total procedure time decreased 54%, volume of contrast
      decreased 44%, and fluoroscopy time decreased 48% (mean change from baseline).
      Selection of angioplasty balloon catheters and stents was improved, and the
      average number of catheters used and stents deployed decreased, although this did
      not reach statistical significance. Faculty observation allowed identification of
      shortcomings of knowledge and skills, including common problems with selection of
      catheter, balloon, and stent sizes; correct positioning of the sheath; and
      intraprocedural monitoring. Postcourse evaluations indicated support for the use
      of simulation in vascular surgery residents' endovascular training. CONCLUSIONS:
      Training with a simulator, incorporated into an individual or small group
      learning session, offers a means to learn and realistically practice endovascular
      procedures without direct risk to patients, with measurable improvements in key
      performance metrics. How simulation training affects subsequent clinical
      performance has yet to be established.

PMID- 17210401
TI  - Carotid plaque instability and ischemic symptoms are linked to immaturity of
      microvessels within plaques.
AB  - BACKGROUND: Instability and rupture of carotid atherosclerotic plaques leads to
      thromboemboli and ischemic symptoms. Angiogenesis occurs within atherosclerotic
      plaques, and plaque vulnerability and symptomatic carotid disease have been
      associated with increased numbers of microvessels. In addition to microvessel
      number, it is possible that the phenotypes of intraplaque vessels could influence
      plaque stability. To test this, the morphology and maturity of vessels within
      plaques from symptomatic and asymptomatic patients was determined. METHODS:
      Carotid plaques were collected after endarterectomy from a cohort of 13
      asymptomatic patients and 30 symptomatic patients. Plaques were sectioned and
      immunostained for the presence of endothelial cells, vascular smooth muscle
      cells, macrophages, and vascular endothelial growth factor. Sections were
      assessed for microvessel morphology, maturity as judged by smooth muscle cell
      cover, and the presence of vascular endothelial growth factor and macrophages.
      RESULTS: Two types of vascular structure were observed within plaques,
      microvessels and dilated, highly irregular multilobular vessels. These irregular
      dysmorphic vessels were found almost exclusively in plaques from symptomatic
      patients. The dysmorphic vessels lacked smooth muscle cells and were highly
      immature. Plaques also contained vascular endothelial growth factor, and this was
      observed adjacent to the dysmorphic vessels. This growth factor was found
      colocalized with macrophages. CONCLUSIONS: Symptomatic carotid plaques contain
      abnormal, immature microvessels similar to those found in tumors and healing
      wounds. Such vessels could contribute to plaque instability by acting as sites of
      vascular leakage by inflammatory cell recruitment. The immature vessels within
      plaques may be therapeutic targets for promoting plaque stabilization.

PMID- 17210402
TI  - Protein kinase C-delta regulates migration and proliferation of vascular smooth
      muscle cells through the extracellular signal-regulated kinase 1/2.
AB  - BACKGROUND: Smooth muscle cell (SMC) migration and proliferation are early and
      crucial events in the pathogenesis of intimal hyperplasia, the primary cause of
      restenosis after vascular intervention. We tested the hypothesis that protein
      kinase C-delta (PKCdelta), a ubiquitously expressed intracellular protein kinase,
      regulates vascular SMC proliferation and migration. METHODS: Exogenous PKCdelta
      was expressed in cultured SMCs via stable transfection or adenovirus-mediated
      gene transfer. Conversely, endogenous PKCdelta was inhibited by means of targeted
      gene deletion (gene knock-out). Cell proliferation and migration were determined
      by (3)H-thymidine incorporation and 24-well transwell assay, respectively.
      RESULTS: We isolated and examined three A10 SMC lines in which PKCdelta was
      stably transfected. Compared with cells that were transfected with an empty
      vector, cells transfected with PKCdelta exhibited reduced ability to proliferate.
      Moreover, PKCdelta transfection inhibited SMC migration toward platelet-derived
      growth factor-BB. Similar inhibitory effects on proliferation and migration were
      also observed when PKCdelta was introduced into primary aortic SMCs via an
      adenoviral vector. Interestingly, SMCs isolated from PKCdelta knockout mice also
      displayed decreased chemotaxis and proliferation compared with PKCdelta(+/+)
      littermates, suggesting a complex yet critical role for PKCdelta. We studied the
      mitogen-activated protein kinase extracellular signal-regulated kinases (ERK) 1/2
      as a possible signaling pathway for PKCdelta's inhibitory effect. PKCdelta
      overexpression diminished ERK1/2 activity. Molecular restoration of ERK
      activation reversed the inhibitory effect of PKCdelta on SMC proliferation and
      migration. CONCLUSIONS: We demonstrate that although normal migration and
      proliferation is lessened in SMCs deficient in PKCdelta, its prolonged activation
      also diminishes those behaviors. This suggests a dual, critical role for PKCdelta
      in SMC proliferation and migration, and thus intimal hyperplasia and restenosis.

PMID- 17210403
TI  - Tumor necrosis factor-alpha and the early vein graft.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the
      blood vessel wall response to hemodynamic forces. We hypothesized that TNF-alpha
      activity drives neointimal hyperplasia (NIH) during vein graft arterialization
      and that anti-TNF-alpha therapy would inhibit NIH. METHODS: Rabbits underwent
      bilateral vein grafting using jugular vein. All distal branches except the
      occipital artery were unilaterally ligated to create distinct flow environments
      between the bilateral grafts. Vein grafts were harvested sequentially up to 28
      days for TNF-alpha messenger RNA (mRNA) quantitation. In separate experiments,
      animals received short-term or long-term dosing with pegylated soluble TNF-alpha
      type I receptor (PEG sTNF-RI) or vehicle. After 14 to 28 days, grafts were
      analyzed for morphometry, proliferation, apoptosis, and PEG sTNF-RI distribution.
      RESULTS: Quantitative mRNA assay (TaqMan) revealed shear-dependent (P < .001) and
      time-dependent (P < .001) TNF-alpha expression. TNF-alpha induction was maximal
      at day 1 and gradually decreased over time, but was persistently elevated even 4
      weeks later (P < .001). Low shear (associated with increased NIH) resulted in
      significantly higher TNF-alpha mRNA expression (P = .03). PEG sTNF-RI was found
      in high concentrations in the serum and localized to NIH. The high-flow and low
      flow vein grafts from treated animals demonstrated similar volumes of NIH
      compared with controls. PEG-sTNF-RI had only modest impact on vascular wall cell
      turnover, as reflected by terminal deoxynucleotide transferase-mediated deoxy
      uridine triphosphate nick-end labeling (P = .064) and anti-Ki-67 (P = .12)
      assays. CONCLUSIONS: Placement of a vein into the arterial circulation acutely
      upregulates TNF-alpha; this expression level correlates with the degree of
      subsequent NIH. Pharmacologic interruption of this signaling pathway has no
      significant impact on NIH or wall cellular proliferation/apoptosis, suggesting
      that early vein graft adaptations can proceed via TNF-alpha-independent
      mechanisms.

PMID- 17210404
TI  - Endovascular repair of an iliac artery aneurysm in a patient with Ehlers-Danlos
      syndrome type IV.
AB  - Ehlers-Danlos type IV (EDS-IV) is an inherited condition most notable for its
      associated vascular complications. Patients are prone to aneurysm formation,
      arterial dissection, and spontaneous vessel rupture. Intervention for the
      vascular pathology of EDS-IV carries high morbidity and mortality. We describe a
      case of a 57-year-old man with EDS-IV and an expanding iliac aneurysm who
      underwent successful endovascular repair with a stent-graft. Endovascular
      aneurysm repair is feasible and should be considered for patients with EDS-IV.

PMID- 17210405
TI  - Combined surgery for the treatment of bilateral subclavian artery aneurysm in
      Marfan syndrome.
AB  - Large bilateral aneurysm of the subclavian artery is an infrequent entity that
      can progress to thrombosis, embolization, or rupture if left untreated. Treatment
      consists of exclusion of the aneurysm by an endovascular procedure or open
      surgery. We present a case of large bilateral subclavian artery aneurysm in a
      patient with Marfan syndrome that was treated by a combination of endovascular
      and conventional surgery. This therapeutic approach provided good results for
      patency with lower morbidity and mortality.

PMID- 17210406
TI  - Repair of recurrent visceral aortic patch aneurysm after thoracoabdominal aortic
      aneurysm repair with a branched endovascular stent graft.
AB  - Aneurysmal degeneration of the visceral aortic patch is an uncommon late
      complication of surgical replacement of the thoracoabdominal aorta. We report on
      a 70-year-old woman who had undergone previous open thoracoabdominal aortic
      aneurysm repair and subsequent revision surgery for a visceral aortic patch
      aneurysm. The patient presented with a recurrent asymptomatic 60-mm-diameter
      visceral aortic patch aneurysm involving the celiac axis and superior mesenteric
      artery. The lesion was successfully treated with a custom-designed Zenith
      branched endovascular stent graft. The patient remains well at 12 months.

PMID- 17210407
TI  - Pseudoaneurysm of the common carotid artery due to ongoing trauma from the hyoid
      bone.
AB  - We report a left common carotid artery pseudoaneurysm in a 47-year-old bricklayer
      with no prior surgical procedures or acute neck injury. At operation, the
      pseudoaneurysm was found to be related to ongoing injury to the carotid artery
      from the tip of the hyoid bone. The most likely explanation for this was that the
      patient's job required that he carry cement panniers weighing about 15 kg on his
      left shoulder and that these panniers repeatedly compressed the left side of his
      neck, thus forcing the carotid against the hyoid.

PMID- 17210408
TI  - Endovascular repair of an acute blunt popliteal artery injury.
AB  - Blunt popliteal arterial injury is uncommon and is usually associated with
      surrounding soft tissue and orthopedic injuries, which may complicate traditional
      open operative repair. We present the successful management of a blunt popliteal
      artery injury through an endovascular approach, where we imaged the lesion,
      extracted the thrombus, protected against distal embolization, and performed a
      balloon angioplasty to the intimal lesion. Our approach is the first documented
      in the literature in which endovascular repair of a blunt popliteal artery injury
      was performed successfully in an acutely ischemic extremity. Using a filter wire
      is a novel way to prevent distal embolization during manipulation.

PMID- 17210409
TI  - Mycotic superior mesenteric aneurysm.

PMID- 17210410
TI  - Challenges and opportunities in abdominal aortic aneurysm research.
AB  - Abdominal Aortic Aneurysms (AAAs) are associated with advanced age, male gender,
      cigarette smoking, atherosclerosis, hypertension, and genetic predisposition.
      Basic research studies have led to a better understanding of aneurysm disease
      over the past two decades. There has also been a growing appreciation that
      fundamental knowledge regarding the process of aneurysmal degeneration is still
      somewhat limited. Opportunities in research include: 1) the investigation of
      potential new mechanism-based pharmacologic interventions; 2) identify the
      genetic basis for an inherited predisposition; 3) develop and refine noninvasive
      approaches for the early detection; 4) examine potential novel surgical
      approaches and design new biomaterials; and 5) initiate and promote awareness
      programs for diagnosis and treatment of aortic aneurysms. The optimal approach to
      addressing these issues will require integrative, multidisciplinary research
      programs that involve basic scientists working in concert with vascular and
      cardiothoracic surgeons, as well as other clinical specialists with expertise in
      vascular disease.

PMID- 17210412
TI  - The Midwestern Vascular Surgical Society: revelations, opportunities, and a sense
      of pride.

PMID- 17210411
TI  - Free-floating thrombus of the carotid artery: literature review and case reports.
AB  - BACKGROUND: Free-floating thrombus (FFT) of the carotid artery is an uncommon
      entity that usually presents as an acute emergency. Management is based on case
      reports and series because the natural history and optimal treatment are unknown.
      This study was conducted to systematically review the world literature in an
      attempt to better understand FFT, its presentation, distribution, management, and
      outcome. METHOD: A literature search in all languages was performed of the PubMed
      database (> or =1950s) and Medline database (1966-November 2004). All relevant
      articles were reviewed and their references analyzed in a similar manner for
      further literature. Cases from the authors' institutions were reviewed as well.
      All cases within the reports were individually assessed for inclusion or
      exclusion. Inclusion required that the FFT originate or anchor within the carotid
      artery (ie, excluding emboli, arch thrombi with extensions into the carotid
      artery), be partially occluding (ie, excluding occlusions, "string-sign,"
      microscopic thrombus), and ideally have an elongated or protrusive morphology,
      circumferential flow around the distal portion, and cyclical motion with the
      cardiac cycles. RESULTS: There were 61 reports reviewed, of which 43 contained
      FFT cases. These reports had 342 cases (including the current series) that were
      reviewed, of which 145 met our inclusion criteria. A database was created for
      qualitative and quantitative assessment of all cases. When data were pooled,
      appropriate statistical analysis was performed. A limitation of the study is that
      FFT is under-reported and ill defined, which limited the analysis in quantity and
      quality. In addition, reporting is not uniform, and therefore, significant data
      were not always present. In attempting to define FFT and include or exclude
      cases, subjectivity is inherent. CONCLUSIONS: FFT is more frequently reported in
      men than women, with a ratio of nearly 2:1 (P < .0001), and at a younger age than
      in most patients with carotid disease (P < .0001 when compared with North
      American Symptomatic Carotid Endarterectomy Trial, European Carotid Surgery
      Trial, and Asymptomatic Carotid Surgery Trial). Symptoms are present in 92% of
      patients. There was a trend for patients with FFT to be hypercoagulable (47% of
      those serologically tested). The internal carotid artery was the most commonly
      affected (75%), with atherosclerosis being the most common associated pathology.
      Medical and surgical management have both been used, with neither clearly
      superior to the other. Medical management for stabilizing neurologic deficits has
      less risk and less benefit than surgical intervention.

PMID- 17210413
TI  - Caseload outcome credentialing: taking from the have-nots.

PMID- 17210414
TI  - Regarding "Protected carotid stenting in high-surgical-risk patients: the ARCHeR
      results".

PMID- 17210417
TI  - Regarding "InterGard silver bifurcated graft: features and results of a
      multicenter study".

PMID- 17210418
TI  - Arthroscopy and antibiotics.

PMID- 17210420
TI  - Antibiotic prophylaxis for arthroscopy of the knee: is it necessary?
AB  - PURPOSE: Our purpose was to determine the incidence of infection after routine
      arthroscopic meniscectomy of the knee with and without preoperative prophylactic
      intravenous antibiotics. METHODS: A retrospective review of 3,231 arthroscopic
      knee surgeries was performed at a physician-owned in-office ambulatory surgery
      center over a 3-year period, of which 2,780 were arthroscopic meniscectomies. The
      cases were evaluated with respect to the incidence of deep infection as evidenced
      by a positive joint aspirate. Approximately 30% of the patients had prophylactic
      intravenous antibiotics within 1 hour before the arthroscopic procedure. RESULTS:
      The infection rate was 0.15% in those patients who received antibiotics and 0.16%
      in those who did not receive antibiotics (P = .59). CONCLUSIONS: The results of
      this study confirm that there is no value in administering antibiotics before
      routine arthroscopic meniscectomy to prevent joint sepsis. LEVEL OF EVIDENCE:
      Level III, retrospective comparative study.

PMID- 17210421
TI  - Double-bundle "anatomic" anterior cruciate ligament reconstruction: a cadaveric
      study of tunnel positioning with a transtibial technique.
AB  - PURPOSE: The aim of this study was to examine whether a double-bundle anterior
      cruciate ligament (ACL) reconstruction with a transtibial approach could position
      the tibial and femoral tunnels accurately in the native bundle attachments.
      METHODS: In 21 fresh-frozen knees the tibial and femoral attachments of the
      anteromedial (AM) and posterolateral (PL) bundles were outlined. The AM tibial
      tunnel guidewire was drilled with the 65 degree Howell tibial guide (Arthrotek,
      Warsaw, IN) located against the femur in the extended knee. The PL tibial wire
      was drilled through a prototype attachment to the Howell guide. Of the knees, 14
      were available for the femoral part of the study. The AM femoral guidewire used
      an aimer offset 3 mm from the over-the-top position. The PL wire was drilled
      transtibially at 70 degrees of flexion, with external rotation and posterior
      drawer loads being applied. The plateaus and condyles were photographed and the
      wire positions measured. RESULTS: With regard to the tibia, 17 of 21 AM wires
      were in the AM bundle attachment (at 61% and 36% of the natural ACL
      posteroanterior and mediolateral length, respectively) and 19 of 21 PL wires were
      in the PL bundle attachment (at 28% and 36% of the posteroanterior and
      mediolateral length, respectively). With regard to the femur, 12 of 14 AM wires
      and 9 of 14 PL wires were in the correct native bundle attachment. The AM wire
      was 3% more shallow than the center of the AM attachment (P = .03) and 6% more
      superior (P < .001), where 100% was the diameter of the posterior lateral
      condyle. The PL wire was 4% more shallow than the center of the PL attachment (P
      = .026) and 6% more superior (P < .001). CONCLUSIONS: Anatomic and reproducible
      tibial guidewire positioning was achieved. Femoral wires were reproducibly
      positioned, but both were superior to and more shallow than the natural ACL
      bundle attachments, so further development or a different approach is
      appropriate. CLINICAL RELEVANCE: The double-bundle reconstruction aims to restore
      anterior drawer and rotational stability. This technique ensures anatomic tibial
      positioning. Further improvements are needed with regard to the femur.

PMID- 17210422
TI  - Initial and 6 weeks postoperative structural properties of soft tissue anterior
      cruciate ligament reconstructions with cross-pin or interference screw fixation:
      an in vivo study in sheep.
AB  - PURPOSE: The purpose of this study was to evaluate the detrimental effects of
      interference screw fixation on soft tissue anterior cruciate ligament (ACL)
      reconstruction after 6 weeks and compare them with a cross-pin technique.
      METHODS: In an intra-articular model, ovine soft tissue grafts were fixed with
      two 3.3-mm biodegradable pins or with interference screws. Maximum load, yield
      load, and stiffness of the femur-graft-tibia complex were evaluated immediately
      after surgery and 6 weeks postoperatively. RESULTS: For knees with interference
      screw fixation, strength deteriorated by 81% and stiffness deteriorated by 67%.
      For knees with double cross-pin fixation, strength deteriorated by 48% and
      stiffness improved by 52%. These differences were statistically significant. At
      the time of surgery, all grafts failed by slippage of the graft past the screw or
      by cross-pin failure. At 6 weeks postoperatively, the grafts of both groups
      failed at the tibial or femoral tunnel entrance. CONCLUSIONS: After 6 weeks, the
      biomechanical characteristics of grafts that were fixed with cross-pins were
      superior to those of grafts after interference screw fixation. CLINICAL
      RELEVANCE: Because of significantly inferior biomechanical stability after
      interference screw fixation, a less aggressive program of rehabilitation might be
      recommended.

PMID- 17210423
TI  - Functional assessment and muscle strength before and after reconstruction of
      chronic anterior cruciate ligament lesions.
AB  - PURPOSE: The goal of this study was to evaluate strength and functional capacity
      before and after anterior cruciate ligament (ACL) reconstruction to determine the
      influences of preoperative strength deficit, graft type, and gender, as well as
      their clinical relevance in predicting postsurgical recovery and determining the
      postoperative rehabilitation program. METHODS: This was a retrospective review of
      prospectively collected uniform data from a group of 191 patients undergoing ACL
      reconstruction. We assessed functional capabilities and strength of the
      quadriceps and hamstring at 60 degrees/s and 180 degrees/s by use of a Cybex II
      dynamometer (Lumex, Ronkonkoma, NY) before and 6, 9, and 12 months after surgery.
      RESULTS: There was a preoperative quadriceps strength deficit and a decreased
      limb symmetry index in patients with an ACL deficiency. This strength deficit
      increased postoperatively, with the highest measured deficit occurring at 6
      months postoperatively and a clear improvement from 6 to 12 months. Functional
      assessment showed identical development. There was a statistically significant
      relation between an increased quadriceps strength deficit preoperatively and poor
      early postoperative functional performance. For the bone-patellar tendon-bone
      (BPTB) group, there was an increased quadriceps strength deficit compared with
      the semitendinosus and gracilis tendon (STG) group, and the STG group had an
      increased hamstring strength deficit on postoperative testing. The postoperative
      hamstring strength deficit is significantly increased in female patients.
      CONCLUSIONS: All of these data suggest that quadriceps strength deficit is
      related to the ACL injury and is increased by ACL reconstruction. Even 1 year
      after ACL reconstruction, a quadriceps strength deficit of almost 20% persists.
      Flexion strength is within the normal range before and after surgery. These
      results are influenced by graft choice, with a higher quadriceps strength deficit
      for BPTB grafts. STG grafts induce a higher hamstring strength deficit compared
      with BPTB grafts. Functional assessment is improved at 9 and 12 months
      postoperatively compared with preoperatively regardless of graft type. However,
      an increased preoperative quadriceps strength deficit results in a lower limb
      symmetry index at 6 and 9 months postoperatively. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series.

PMID- 17210424
TI  - Three-dimensional computed tomographic scan of the external third of the
      clavicle.
AB  - PURPOSE: The aims of this radiologic study were to explore the anatomic aspect of
      the external third of the clavicle and to determine anatomic elements that can be
      useful for surgeons who perform surgery that involves this area. METHODS: Twenty
      patients with healthy acromioclavicular (AC) joints underwent computed
      tomographic (CT) scan for assessment of the lateral clavicle. Three-dimensional
      reconstruction of the AC joint and of the external third of the clavicle was
      performed. The axis of the external third was determined by CT scan
      reconstruction. Two-dimensional reconstructions were performed perpendicular to
      this axis; each involved 5 mm for exploration of the size of the 4 cortical bones
      and of the inner diameter of the clavicle. RESULTS: The average size of the
      external third before the anterior curve of the clavicle was 40 mm. The average
      inner diameter of the clavicle ranged from 8.24 to 4.7 mm when measured medially,
      but many differences were noted between patients. The upper cortical bone was
      thicker than 2 mm at an average of 17 mm from the AC joint. Three forms of the
      external third of the clavicle were identified: truncated (n = 6), conical (n =
      4), and cylindrical (n = 10). The projection of the axis of the external third of
      the clavicle at the external side of the acromial bone ranged from 4.8 to 21 mm
      (average, 12.42 mm) at the backward anterior side of the acromial bone.
      CONCLUSIONS: Our study shows the great variability of the anatomy of the external
      third of the clavicle. CLINICAL RELEVANCE: Anatomic data should be useful for
      surgeons who perform fixation or resection of the distal part of the clavicle.

PMID- 17210425
TI  - Arthroscopic release of suprascapular nerve entrapment at the suprascapular
      notch: technique and preliminary results.
AB  - PURPOSE: We describe a novel all-arthroscopic technique for suprascapular nerve
      (SSN) decompression and present our preliminary results for this procedure.
      METHODS: A prospective series of 10 patients with preoperative electromyographic
      findings consistent with chronic SSN compression, posterior shoulder pain, and
      subjective weakness were treated with arthroscopic SSN decompression. There were
      8 men and 2 women, with a mean age of 50 years. The mean follow-up was 15 months
      (range, 6 to 27 months). In 8 of 10 patients, we performed an electromyographic
      examination postoperatively to evaluate nerve recovery after decompression. The
      clinical outcomes measures used to assess preoperative and postoperative function
      were the visual analog scale for pain, the Constant score, strength testing of
      the supraspinatus and infraspinatus, and a subjective satisfaction questionnaire.
      In all patients preoperative and postoperative computed tomography arthrograms
      were obtained to document the absence of a rotator cuff tear. RESULTS: There were
      no complications resulting from SSN decompression. Of 10 patients, 8 had
      postoperative electromyography at a mean of 6 months after SSN release and 2
      refused to undergo this study after surgery. Of the 8 postoperative
      electromyograms, 7 had complete normalization of the latency in the motor fibers
      of the SSN and normalization of the voluntary motor action potential for the
      supraspinatus and infraspinatus muscles. Two of the electromyograms showed
      evidence of partial recovery. The preoperative and postoperative Constant scores
      for these patients were 60.3 and 83.4, respectively (P < .001). All patients
      returned to their normal work and sports activity at a mean of 3 weeks (range, 2
      days to 3 months). The abduction and external rotation strength also
      significantly improved. At the time of last follow-up, 9 patients graded their
      clinical outcome as excellent and responded that they had complete relief of
      pain. One of the study subjects reported a satisfactory result with moderate
      relief of pain. CONCLUSIONS: Arthroscopic release of the SSN can be performed
      safely and effectively. All of the patients in this preliminary study had
      improvement in their postoperative electromyographic findings and had marked
      improvement in pain relief and function. LEVEL OF EVIDENCE: Level IV, therapeutic
      case series.

PMID- 17210426
TI  - Value of preoperative ultrasound marking of calcium deposits in patients who
      require surgical treatment of calcific tendinitis of the shoulder.
AB  - PURPOSE: The objective of our study was to evaluate whether preoperative
      ultrasound-guided marking of calcium deposits has a positive effect on the
      efficiency and speed of localization of calcium deposits during surgery, and
      whether this technique is a factor that increases the probability of good
      clinical results. METHODS: Twenty-four patients who required surgery for calcific
      tendinitis in the years 2001 and 2002 were divided into 2 groups of 12 patients
      by week. Before undergoing surgery, those in group 1 (weeks 1, 3, 5, etc.) were
      given a standard ultrasound examination, along with preoperative ultrasound
      guided marking (pre-USM) of calcium deposits, whereas group 2 (weeks 2, 4, 6,
      etc.) received the standard ultrasound examination without pre-USM. In both
      groups, arthroscopic removal of calcium deposits was carried out and the
      postoperative treatment plan was identical. The clinical result was evaluated by
      the Constant-Murley score. RESULTS: At the 6-week and 2-year follow-up visits,
      the clinical result was significantly better (P < .05) in the pre-USM group than
      in the unmarked group (Constant score of 76 v 70 points and 80 v 74 points,
      respectively). After 12 weeks, the clinical outcomes of both groups showed an
      approaching significance, with better results seen in the pre-USM group (79 v 74
      points; P = .052). The time required for intraoperative localization of calcium
      deposits was 16 versus 22 minutes. The difference showed an approaching
      significance (P = .057). Removal of calcium was possible in 12 versus 10 cases;
      complete removal was possible in 8 versus 6 cases, respectively. However, none of
      these variables had a statistically significant influence on our results.
      CONCLUSIONS: Preoperative ultrasound-guided marking of calcific deposits is a
      procedure that statistically significantly improves the clinical results of
      arthroscopic surgery as seen at 6 weeks and 2 years; statistical significance of
      .052 was approached only at 12 weeks, as we have shown here for calcifying
      tendinitis of the shoulder joint. LEVEL OF EVIDENCE: Level III, development of
      diagnostic criteria with nonconsecutive patients.

PMID- 17210427
TI  - Glove tears during arthroscopic shoulder surgery using solid-core suture.
AB  - PURPOSE: Surgeons have noticed an increased incidence of finger lacerations
      associated with arthroscopic knot tying with solid-core suture material. This
      study examines glove perforations and finger lacerations during arthroscopic
      shoulder surgery. METHODS: We collected 400 surgical gloves from 50 consecutive
      arthroscopic shoulder repair procedures using No. 2 solid-core sutures. Two
      surgeons using double gloves were involved in every case, with one being
      responsible for tying all knots. Powder-free latex gloves were worn in all cases.
      Knots consisted of a sliding stitch of the surgeon's preference followed by 3
      half-hitches via a knot-pusher instrument. All gloves were inspected grossly and
      then tested for tears with an electroconductivity meter. RESULTS: The knot-tying
      surgeon had significantly more glove tears than the control (P < .01). Tears were
      localized to the radial side of the index finger of the glove at the distal
      interphalangeal joint in all cases. Of the tying surgeon's gloves, 68 (34%) were
      found to have tears. These included 17 inner gloves (17%) and 51 outer gloves
      (51%). If an inner glove was torn, the corresponding outer glove was torn in all
      cases. A mean of 3.96 knots were tied in each case. There was a significantly
      higher incidence of inner glove tears when more than 3 knots were tied (P < .03).
      There was no significant difference in glove tears between suture types. Finger
      lacerations did occur in the absence of glove tears. However, in the presence of
      an inner glove tear, there was a statistically significant association with a
      finger laceration at the corresponding level (P < .03). CONCLUSIONS:
      Intraoperative glove tears and subsequent finger lacerations occur with a high
      frequency when arthroscopic knots are tied with solid-core suture material. Risk
      can potentially be minimized by frequent glove changes or use of more durable,
      less penetrable gloves. CLINICAL RELEVANCE: This study addresses surgeon and
      patient safety during arthroscopic shoulder surgery.

PMID- 17210428
TI  - The "purse-string" technique: an arthroscopic technique for stabilization of
      anteroinferior instability of the shoulder with early and medium-term results.
AB  - PURPOSE: We report the early and midterm results of the "purse-string" technique,
      a simple, new arthroscopic technique for stabilization of anteroinferior
      instability of the glenohumeral joint that addresses both the Bankart lesion and
      capsular stretching. METHODS: The patients comprised 36 individuals (37
      shoulders), with a mean age of 26 years, who had recurrent anteroinferior post
      traumatic instability as a result of a traumatic Bankart lesion. They had
      sustained a mean of 5 dislocations per shoulder (range, 1 to 11). The cohort
      included 5 professional and 6 semiprofessional athletes, all of whom were
      involved in collision or overhead sports. A purse-string suture anchor at the 4
      o'clock position was used to ensure a purse-string effect in tightening the
      capsule in the inferior-superior plane and creation of anterior glenoid bumper.
      All of the patients were assessed by an independent investigator (T.M.) at a mean
      of 36 months (range, 27 to 87 months) after surgery. RESULTS: Postoperatively,
      the mean Rowe score was 93 (range, 55 to 100), the mean Walch-Duplay score was 93
      (range, 70 to 100), and the mean Constant score was 97 (range, 77 to 100). Of the
      patients, 97% returned to the same sport that they had played before injury.
      Furthermore, 66% of patients returned to their preinjury level of sports, and all
      of the professional athletes resumed full activities. One patient continued to
      have symptoms of instability, and one patient had a further dislocation after a
      new traumatic event. CONCLUSIONS: The early and medium-term results obtained are
      very encouraging, with a rate of failure of only 5.4%, a high level of return to
      preinjury sporting activities (with 97% of patients returning to the same sport
      and 66% returning to their preinjury level of sports), and a high patient
      satisfaction rate (with excellent or good results in 94% of patients). LEVEL OF
      EVIDENCE: Level IV, therapeutic case series.

PMID- 17210429
TI  - Pain scores in the management of postoperative pain in shoulder surgery.
AB  - PURPOSE: Recent public opinion has focused on the lay perception that
      postoperative pain control is inadequate. The Joint Commission on Accreditation
      of Healthcare Organizations has attempted to address this issue by mandating
      patient-reported numeric pain scores as part of postoperative pain assessment. No
      studies exist to validate these scores in orthopaedics. The purpose of this study
      was 3-fold: (1) to determine which preoperative variables were associated with
      elevated postoperative pain scores, (2) to identify whether pain scores
      correlated with more traditional signs and symptoms of pain, and (3) to identify
      whether patients with a high pain score (HPS) affect perioperative and
      postoperative complication rates. METHODS: We retrospectively evaluated 105
      patients who underwent routine arthroscopic rotator cuff repair over a 12-month
      period. Correlations and linear regression analysis were used to assess factors
      associated with postoperative pain scores. Logistic regression analysis was used
      to construct a model of preoperative, demographic, surgical, and postoperative
      variables associated with HPSs. RESULTS: Wide variability existed in pain scores
      despite the similarity of the surgical stimulus. What subtle differences that
      were present in the surgical procedures had no bearing on pain scores. No
      correlation existed between pain scores and any physiologic correlate of pain.
      Pain scores were correlated with Workers' Compensation insurance, preoperative
      antianxiety medications, antidepressant medications, preoperative narcotics, and
      alcohol use. HPS patients had a longer recovery room stay (P < .05) and a higher
      incidence of postoperative nausea than those with a normal pain tolerance. HPS
      patients also had a significantly delayed return to work, as well as
      significantly lower Simple Shoulder Test scores at 6 weeks, although the final
      shoulder scores were similar to those in patients with a normal pain tolerance.
      CONCLUSIONS: Patient-reported pain scores have been mandated, but they vary
      widely among patients undergoing virtually the same procedure and correlate
      poorly with physiologic manifestations of pain. Pain scores tend to correlate
      with other types of variables, most of which would be expected by the experienced
      surgeon. The exclusive use of pain scores in postoperative pain management should
      be limited to prevent complications. LEVEL OF EVIDENCE: Level IV, prognostic case
      series.

PMID- 17210430
TI  - Anterior and posterior instability of the long head of the biceps tendon in
      rotator cuff tears: a new classification based on arthroscopic observations.
AB  - PURPOSE: The purpose of this study was to evaluate arthroscopically the frequency
      and type of instability of the long head of the biceps (LHB) tendon in patients
      undergoing rotator cuff repair. METHODS: In 200 consecutive patients undergoing
      arthroscopic rotator cuff repair, LHB instability was assessed statically and
      dynamically in the anteroposterior direction. In addition, macroscopic lesions of
      the LHB, as well as lesions of the adjacent rotator cuff tendons, were
      documented. RESULTS: LHB instability (subluxation or dislocation) was found in
      45% of patients, with isolated anterior instability in 16%, isolated posterior
      instability in 19%, and combined anteroposterior instability in 10%. Whereas LHB
      subluxations were observed in both directions, dislocations were only seen in
      anterior LHB instability. Anterior instability was more associated with a
      subscapularis lesion, whereas posterior instability was more associated with a
      supraspinatus tear. Lesions of the LHB tendon were strongly associated with LHB
      instability and the size of the rotator cuff tear. CONCLUSIONS: In 200 patients
      with rotator cuff tears LHB instability could be observed arthroscopically in
      45%, with 16% being anterior, 19% being posterior, and 10% being anteroposterior.
      LHB instability was associated with LHB lesions, with 15% of the LHB tendons
      showing a normal appearance when unstable versus 70% when stable. Preoperative
      O'Brien and Speed tests did not correlate with intraoperative observed LHB
      pathology. The size of the rotator cuff tear could be correlated with the grade
      of LHB lesion, becoming more significant with augmenting tear size. On the basis
      of these observations, we created a new arthroscopic classification of LHB
      instability with respect to the direction and extent of LHB instability, lesions
      of the LHB, and status of the adjacent rotator cuff tendons. LEVEL OF EVIDENCE:
      Level IV, diagnostic study with poor reference standard.

PMID- 17210431
TI  - Arthroscopic rotator cuff repair with and without subacromial decompression: a
      prospective randomized study.
AB  - PURPOSE: Our purpose was to evaluate the role of subacromial decompression in the
      arthroscopic repair of full-thickness rotator cuff tears in a prospective
      randomized clinical study. METHODS: Arthroscopic cuff repair was performed in 80
      patients with a full-thickness rotator cuff tear. They were divided into 2 groups
      comprising 40 patients each. In group 1 arthroscopic rotator cuff repair was
      performed with subacromial decompression. In group 2 the repair was performed
      without decompression. Rotator cuff tears were repaired via metal suture anchors
      for tendon-to-bone repair, side-to-side repair, or a combination of the 2
      techniques. Results were evaluated by use of the Constant score normalized for
      age and gender, as well as the Disabilities of the Arm, Shoulder and Hand (DASH)
      and Work-DASH self-administered questionnaires. On analyzing the results at 2
      years' follow-up, we considered the following independent variables: age; gender;
      dominance; location, shape, area, retraction, and reducibility of cuff tear;
      fatty degeneration; involvement of subscapularis tendon; treatment of biceps
      tendon; rotator cuff repair technique; and type of acromion. A univariate and
      multivariate statistical analysis was performed to determine which variables were
      independently associated with the outcome. RESULTS: Comparison between the groups
      did not show significant differences for each variable considered. The overall
      results for the Constant score were 103.6 points in group 1 and 96.1 points in
      group 2; those for the DASH score were 18.2 points and 23.1 points, respectively;
      and those for the Work-DASH score were 23.7 points and 26.2 points, respectively.
      Univariate and multivariate analysis showed that the following variables
      significantly and independently influenced the outcome: age; shape, retraction,
      and reducibility of cuff tear; fatty degeneration; involvement of subscapularis;
      and repair technique. Subacromial decompression did not influence the outcome
      significantly for each scoring system considered. CONCLUSIONS: At short-term
      follow-up, subacromial decompression did not seem to significantly affect the
      outcome of arthroscopic rotator cuff repair. Longer follow-up studies will be
      necessary to confirm the clinical relevance of these observations. LEVEL OF
      EVIDENCE: Level I, randomized controlled trial with no significant difference but
      narrow confidence intervals.

PMID- 17210432
TI  - Intra-articular fibrous tissue formation following ankle fracture: the
      significance of arthroscopic debridement of fibrous tissue.
AB  - PURPOSE: The purposes of this study were to understand the clinical consequences
      of arthrofibrosis following surgical reduction of ankle fractures and to examine
      the effectiveness of arthroscopic debridement. METHODS: Subjects included 33
      patients (26 males, 7 females) aged 14 to 78 years (mean, 40.2 years) who had
      undergone open reduction and internal fixation of ankle fractures between May
      2000 and May 2003. Arthroscopic examination was performed at the time of implant
      removal after an average of 12.4 months (range, 6 to 43 months), and abnormal
      fibrous tissue, when present, was removed through arthroscopy. The mean follow-up
      period after arthroscopy was 43.7 months (range, 22 to 68 months). Clinical
      outcomes before and after arthroscopy were evaluated with the American
      Orthopaedic Foot and Ankle Society scale and our own functional evaluation
      method. Arthroscopic findings, including the degree of articular cartilage damage
      and the quantity of fibrous tissue, were scored on a 3-point scale. RESULTS:
      Functional deterioration of the ankle joint was observed in 27% of subjects.
      Arthroscopy showed articular cartilage damage in 33% of patients and
      arthrofibrosis in 73%. In patients with functional deterioration, the rate of
      articular cartilage damage was 78%, and arthrofibrosis was present in all cases.
      Furthermore, when extensive fibrosis and impingement on the articular surface
      were present, 88% of patients showed impaired articular function. Arthroscopic
      debridement of fibrous tissue resulted in improved articular function in 89% of
      patients with functional deterioration of the ankle joint before arthroscopy.
      CONCLUSIONS: Arthrofibrosis following ankle fracture causes an unfavorable
      surgical outcome, and arthroscopic debridement of fibrous tissue is an effective
      means of improving articular function. LEVEL OF EVIDENCE: Level IV, therapeutic
      case series.

PMID- 17210433
TI  - Biomechanical fixation in arthroscopic rotator cuff repair.
AB  - Rotator cuff repair remains a challenging and rapidly evolving field. Several
      recent studies have shown that arthroscopic repair yields functional results
      similar to those of mini-open and open procedures, with all of the benefits of
      minimally invasive surgery. However, the "best" repair construct remains
      relatively unknown, with wide variations in surgeon preference and conflicting
      evidence in the literature. The most recent developments in basic science, suture
      and suture anchor technology, and innovative prospects for arthroscopic rotator
      cuff repair are reviewed.

PMID- 17210434
TI  - Arthroscopic-assisted core decompression of the humeral head.
AB  - Humeral head osteonecrosis is a progressive disease that requires prompt
      diagnosis and treatment. Core decompression is a viable treatment option for
      early-stage cases. Most surgeons perform core decompression by arthroscopically
      visualizing the necrotic area of bone and using a cannulated drill to take a
      core. Several attempts are frequently needed to reach the proper location. In the
      hip multiple passes are associated with complications. We describe the use of an
      anterior cruciate ligament (ACL) tibial drill guide to precisely localize the
      area of necrotic bone. Diagnostic arthroscopy is performed to assess the areas of
      osteonecrosis. Core decompression is performed by use of an ACL tibial guide,
      brought in through the anterior or posterior portal to precisely localize the
      necrotic area in preparation for drilling. Under image intensification, Steinmann
      pins are advanced into the area of osteonecrosis. Once positioned, several 4-mm
      cores are made. We treated 3 patients with this technique, and all had immediate
      pain relief. The use of the ACL guide allows precise localization of the area of
      humeral head involvement and avoids multiple drillings into unaffected areas.
      Initial indications are that arthroscopic-assisted core decompression with an ACL
      guide is an effective alternative to previously used methods.

PMID- 17210435
TI  - Reverse rotator interval closure.
AB  - We describe a technique for reducing capsular volume arthroscopically by shifting
      the anterior inferior glenohumeral ligament (AIGHL) and capsule up to the top of
      the subscapularis. This procedure is performed when laxity exists in the absence
      of a Bankart lesion. The AIGHL is first released from the capsule. This allows
      sutures to be placed through the capsule inferiorly so that it can be shifted up
      superiorly during the repair. The AIGHL and capsule are then released from the
      underlying subscapularis. Sutures are then passed through the capsule and out of
      the accessory anterior portal, progressing laterally. A BirdBeak suture passer
      (Arthrex, Naples, FL) is inserted through the superior edge of the subscapularis
      and is used to grasp each undersurface strand of suture and pull it through and
      out of the anterior portal. The sutures are then tied sequentially, effectively
      shifting the capsule and ligament up in a superior direction.

PMID- 17210436
TI  - Arthroscopic reduction-association of the scapholunate.
AB  - The reduction-association scapholunate (RASL) procedure for stabilization of the
      scapholunate joint is an alternative to soft-tissue procedures that do not
      maintain normal carpal alignment, despite reports of good symptomatic relief. The
      RASL procedure--indicated for patients with scapholunate instability or
      scapholunate dissociation without arthritis and, in selected cases, with stage 1
      scapholunate advanced collapse of the wrist--can be performed arthroscopically.
      Radial midcarpal and 3-4 radiocarpal portals are used to excoriate and prepare
      the scapholunate joint surfaces. By use of 0.62'' K-wire joysticks in the lunate
      and distal pole of the scaphoid, the scaphoid undergoes dorsiflexion and
      supination while the lunate undergoes palmarflexion to achieve reduction. A .35''
      guidewire is advanced through the scaphoid waist, across the scapholunate joint
      to the proximomedial corner of the lunate. Supplemental K-wire fixation, from the
      scaphoid to the capitatum and lunate to the radius, stabilizes the reduction for
      placement of a cannulated HBS screw (Orthosurgical Implants, Miami, FL) through a
      1-2 portal, while reduction and positioning are confirmed arthroscopically.
      Arthroscopy facilitates anatomic reduction of the joint, as well as the
      critically important, precise placement of the cannulated HBS screw, by use of 3
      portals rather than the traditional 2-incision approach.

PMID- 17210437
TI  - Use of an independent skeletal distractor in hip arthroscopy.
AB  - Distraction of the hip joint plays an important role in hip arthroscopy by
      improving visualization of and access to intra-articular structures. Distraction
      is usually performed by use of a standard traction table and foot plate, with the
      patient in either the supine or lateral position. Between 1996 and 2005 at our
      institution, we have used an inexpensive, independent, sterile radiolucent
      skeletal distractor device to perform hip arthroscopy in the lateral position
      successfully in 156 cases for a variety of indications and procedures. The device
      consists of a perineal post, a longitudinal distraction beam, and a telescoping
      distraction carriage fitted with a screw drive for attachment to a distal femoral
      K-wire. Skeletal traction is applied against the perineal post through the K-wire
      via the action of the distraction carriage and fine-tuned with the screw drive,
      affording excellent visualization of intra-articular structures. The use of this
      device during hip arthroscopy negates the need for a fracture table, enables the
      surgeon to remain sterile and still manipulate the traction apparatus
      intraoperatively, and provides for simultaneous hip and knee flexion to relax the
      sciatic nerve. Its modular design and small size make hip arthroscopy possible in
      almost all settings, including outpatient operating rooms.

PMID- 17210438
TI  - Hip arthroscopy without a perineal post: a safer technique for hip distraction.
AB  - Pudendal nerve palsy is a reported complication of hip arthroscopy. We report a
      technique using a deflated taped beanbag rather than a perineal post. The patient
      is placed in the supine or lateral position on a fracture table. The beanbag is
      contoured around the patient's flank and thorax. The distal aspect of the beanbag
      is placed no further than the iliac crest, and care is taken to avoid compression
      of the posterior aspect of the axillary region or the posterior humerus. The
      molded beanbag is deflated, a blanket is positioned over the abdomen and lower
      thorax, and with the use of 3-in-wide cloth tape, the patient and beanbag are
      secured to the operative table circumferentially. The superior margin of the
      deflated beanbag remains firm, preventing compression of the thorax and avoiding
      compromised ventilation. The arm on the operative side is placed across the chest
      and secured to avoid obstruction of the operative field. This patient positioning
      provides sufficient stability for adequate traction and good visualization while
      minimizing the risk of a pudendal nerve palsy.

PMID- 17210439
TI  - Medial patellofemoral ligament reconstruction: a novel technique using the
      patellar ligament.
AB  - In patients with chronic patellofemoral instability, more than 2 episodes of
      dislocation, and an anterior tuberosity trochlear groove of less than 20 mm as
      measured on computed tomography or nuclear magnetic resonance imaging, we have
      developed a technique for medial patellofemoral ligament reconstruction that uses
      a medial strip of the patellar ligament (PL). The incision started proximally at
      the level of the superior margin of the patella, centrally between the patellar
      medial margin and the medial epicondyle. A descending incision was then made,
      directed toward the superomedial margin of the tibial tubercle. We performed a
      plane-by-plane dissection up to the peritenon of the PL. With an osteotome, we
      could remove a 2-cm bone fragment concerning the medial third of the distal
      insertion of the PL or keep the distal end free. Using a No. 11 scalpel blade, we
      carefully detached the PL from the patella up to the transition between the
      proximal third and medial third of the patella. We placed the stitches between
      the periosteum and the ligament using FiberWire absorbable threads (Arthrex,
      Naples, FL) to safely rotate the graft. After that, we dissected the medial
      capsule and approached the femoral medial epicondyle. Then we placed a Krackow
      suture in the free tendon end using absorbable threads or anchored the threads
      into 2 holes that were previously drilled, and we secured the end with an
      absorbable interference screw or anchors. The fixation should be performed with
      the knee at 15 degrees to 30 degrees of flexion. Then we sutured the distal edge
      of the vastus medialis muscle to the graft, which bestows a dynamic component
      upon the reconstruction, and we immobilized the knee with a removable brace.

PMID- 17210440
TI  - Anterior cruciate ligament double-bundle reconstruction with hamstring tendon
      autografts.
AB  - The anterior cruciate ligament (ACL) surgical technique via a 5-strand hamstring
      tendon autograft is designed with a conventional single-bundle reconstruction
      that has shown favorable results and an additional posterolateral (PL) bundle
      reconstruction. The conventional single-tunnel technique is performed for the
      tibial tunnel, and the double-tunnel technique is performed for the femoral
      tunnel. The anteromedial (AM) femoral tunnel is prepared with 1 mm of the
      posterior femoral cortex being left over the top at the 11- to 1-o'clock
      position. The PL femoral tunnel is prepared with the outside-in technique by use
      of a 4.5-mm cannulated reamer. The AM bundle is fixed with a rigid fixation
      system on the femoral side, and the PL bundle is fixed to tie with the miniplate
      from the outside femur. A double-bundle reconstruction with 5-strand hamstring
      autografts, in conjunction with a conventional AM bundle and an additional PL
      bundle, seems to be a very effective method for the treatment of ACL
      instabilities. Although the long-term clinical outcome of the procedure is yet to
      be determined, complications including graft impingement, limitation in range of
      motion, and residual instability have not been observed to date in the first 38
      patients who have undergone our technique.

PMID- 17210441
TI  - Arthroscopic treatment of chronic anterior instability of the shoulder in
      Marfan's syndrome.
AB  - We present a case of recurrent anterior shoulder dislocation in a patient with
      Marfan's syndrome who presented with hyperlaxity that has been treated
      arthroscopically. We discuss abnormal findings at arthroscopic evaluation,
      including complete absence of the mid anterior capsule, which left the
      subscapularis uncovered, and we hypothesize that repetitive trauma to the capsule
      was not followed by a normal process of remodeling because of a lack of competent
      elastic fibers and a poor capacity for soft tissue healing. The inferior
      insertion of the labrum and the inferior glenohumeral ligament seemed normal
      through the large volume of the pouch. We performed arthroscopic reconstruction
      of the capsule through dissection of its anteroinferior part with a
      radiofrequency wand from the glenoid rim and the subscapularis, followed by
      superior drift of the capsule. The Weitbrecht foramen was then closed with 2
      nonresorbable No. 4 sutures, and the capsule was reinserted to the labrum with 2
      anchors. A final suture closed the remaining hole in the rotator interval. At 16
      month follow-up, the patient emphasized her satisfaction with the results; she
      was able to keep up with her regular schedule of leisure sports and swimming,
      painlessly, with no limitations or new episodes of instability.

PMID- 17210442
TI  - Tumor-like meniscal cyst.
AB  - A 50-year-old woman presented with a 5-year history of mild pain in her right
      knee, which had increased over the last 2 years. A palpable mass over the
      anterolateral aspect of the knee was obvious and the last 3 months she was
      experiencing locking episodes with consequent knee effusion. The differential
      diagnosis was driven between meniscal cyst, pigmented villonodular synovitis,
      synovial sarcoma, synovial chondromatosis, and aneurysm. After a diagnostic
      arthroscopy, the lesion was excised by a limited lateral arthrotomy. The
      pathologic findings revealed a synovial cyst. Intra-articular synovial cysts are
      uncommon, nonsymptomatic, and mostly incidental findings on magnetic resonance
      imaging (MRI) and arthroscopy. This lateral meniscus synovial cyst (2.5 x 2.5 cm)
      was enlarged within the intracondylar notch and produced disabling knee symptoms.
      The peculiarity of this lesion was the tumor-like appearance: its large size, the
      progress of symptoms, and the multilobulated, nonhomogenous signal on the MRI
      scan. One year postoperatively, the patient is asymptomatic and the MRI obtained
      at 6 months revealed no remnant of the fully excised cyst.

PMID- 17210443
TI  - Acute rupture of the anterior cruciate ligament and patellar tendon in a
      collegiate athlete.
AB  - In rare incidences of combined ruptures of the ACL and patellar tendon, either
      the patellar tendon ruptures or the associated ACL tear is often initially
      missed. Even when recognized, there is no established treatment regimen. We
      report a case of an intercollegiate football player with a combined rupture of
      the ACL and patellar tendon that was successfully treated by primary augmented
      repair of the patellar tendon along with ACL reconstruction. Similar to other
      reported cases, the mechanism of injury involved forceful eccentric contraction
      of the quadriceps against a fixed foot. Superior displacement of the patella with
      a palpable defect of the patellar tendon, a positive Lachman test, and an
      inability to perform terminal knee extension noted during the on-field
      examination indicated the combined injury. Magnetic resonance and radiographic
      imaging confirmed conclusions from the on-field examination. The patient also
      underwent safe early mobilization and weight bearing following surgical repair.

PMID- 17210444
TI  - Modulation of pregnane X receptor- and electrophile responsive element-mediated
      gene expression by dietary polyphenolic compounds.
AB  - Based on animal models, dietary polyphenols are predicted to be promising
      chemopreventive agents in humans. Allspice, clove, and thyme extracts as well as
      defined dietary polyphenolic compounds were, therefore, tested for their ability
      to activate mechanisms related to phase 1 enzymes, i.e., the PXR-regulated CYP3A4
      promoter, and phase 2 enzymes, i.e. the EpRE-regulated promoters of
      gastrointestinal glutathione peroxidase (GI-GPx) and heme oxygenase-1 (HO-1),
      examples of Nrf2-regulated genes. From the compounds tested, clove and thyme
      extracts as well as curcumin and resveratrol activated the PXR. PXR activation
      correlated with the activation of the CYP3A4 promoter in the case of thyme
      extract, curcumin, and resveratrol, but not in the case of clove extract.
      Allspice extract, EGCG, and quercetin did not activate PXR but enhanced CYP3A4
      promoter activity. Thyme extract and quercetin activated the EpRE of HO-1. Both
      significantly activated the GI-GPx promoter, effects that depended on a
      functional EpRE. Resveratrol did not activate the isolated EpRE but enhanced the
      GI-GPx promoter activity, whereas clove extract even inhibited it. It is
      concluded that individual polyphenols as well as polyphenol-rich plant extracts
      may affect phase 1 and 2 enzyme expression by distinct mechanisms that must be
      elucidated, before potential health effects can reliably be predicted.

PMID- 17210445
TI  - Reactions of yeast thioredoxin peroxidases I and II with hydrogen peroxide and
      peroxynitrite: rate constants by competitive kinetics.
AB  - Peroxiredoxins are receiving increasing attention as defenders against oxidative
      damage and sensors of hydrogen peroxide-mediated signaling events. Likely to be
      critical for both functions is a rapid reaction with hydrogen peroxide, typically
      with second-order rate constants higher than 10(5) M(-1) s(-1). Until recently,
      however, the values reported for these rate constants have been in the range of
      10(4)-10(5) M(-1) s(-1), including those for cytosolic thioredoxin peroxidases I
      (Tsa1) and II (Tsa2) from Saccharomyces cerevisiae. To resolve this apparent
      paradox, we developed a competitive kinetic approach with horseradish peroxidase
      to determine the second-order rate constant of the reaction of peroxiredoxins
      with peroxynitrite and hydrogen peroxide. This method was validated and allowed
      for the determination of the second-order rate constant of the reaction of Tsa1
      and Tsa2 with peroxynitrite (k approximately 10(5) M(-1) s(-1)) and hydrogen
      peroxide (k approximately 10(7) M(-1) s(-1)) at pH 7.4, 25 degrees C. It also
      permitted the determination of the pKa of the peroxidatic cysteine of Tsa1 and
      Tsa2 (Cys47) as 5.4 and 6.3, respectively. In addition to providing a useful
      method for studying thiol protein kinetics, our studies add to recent reports
      challenging the popular belief that peroxiredoxins are poor enzymes toward
      hydrogen peroxide, as compared with heme and selenium proteins.

PMID- 17210446
TI  - Sustained formation of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone radical
      adducts in mouse liver by peroxisome proliferators is dependent upon peroxisome
      proliferator-activated receptor-alpha, but not NADPH oxidase.
AB  - Reactive oxygen species are thought to be crucial for peroxisome proliferator
      induced liver carcinogenesis. Free radicals have been shown to mediate the
      production of mitogenic cytokines by Kupffer cells and cause DNA damage in rodent
      liver. Previous in vivo experiments demonstrated that acute administration of the
      peroxisome proliferator di(2-ethylhexyl) phthalate (DEHP) led to an increase in
      production of alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) radical
      adducts in liver, an event that was dependent on Kupffer cell NADPH oxidase, but
      not peroxisome proliferator-activated receptor (PPAR)alpha. Here, we hypothesized
      that continuous treatment with peroxisome proliferators will cause a sustained
      formation in POBN radical adducts in liver. Mice were fed diets containing either
      4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (WY-14,643, 0.05% w/w) or
      DEHP (0.6% w/w) for up to 3 weeks. Liver-derived radical production was assessed
      in bile samples by measuring POBN radical adducts using electron spin resonance.
      Our data indicate that WY-14,643 causes a sustained increase in POBN radical
      adducts in mouse liver and that this effect is greater than that of DEHP. To
      understand the molecular source of these radical species, NADPH oxidase-deficient
      (p47phox-null) and PPARalpha-null mice were examined after treatment with WY
      14,643. No increase in radicals was observed in PPARalpha-null mice that were
      treated with WY-14,643 for 3 weeks, while the response in p47phox-nulls was
      similar to that of wild-type mice. These results show that PPARalpha, not NADPH
      oxidase, is critical for a sustained increase in POBN radical production caused
      by peroxisome proliferators in rodent liver. Therefore, peroxisome proliferator
      induced POBN radical production in Kupffer cells may be limited to an acute
      response to these compounds in mouse liver.

PMID- 17210447
TI  - Discoidin domain receptor 1 mediates collagen-induced nitric oxide production in
      J774A.1 murine macrophages.
AB  - Nitric oxide (NO) is an important regulator of immune responses. Effects of
      cytokines, such as tumor necrosis factor (TNF)-alpha or IFN-gamma, and bacterial
      products, such as lipopolysaccharide, on macrophage NO production have been well
      documented; however, the role of the extracellular matrix proteins, including
      collagen, in this process remains unclear. We previously reported that discoidin
      domain receptor 1 (DDR1), a nonintegrin collagen receptor, was expressed in human
      macrophages, and its activation facilitated their differentiation as well as
      cytokine/chemokine production. Here, we examined the role for DDR1 in collagen
      induced NO production using the murine macrophage cell line J774 cells that
      endogenously express DDR1. Activation of J774 cells with collagen induced the
      expression of inducible NO synthase (iNOS) and NO production. Inhibition of DDR1,
      but not beta1-integrins, abolished collagen-induced iNOS and NO production.
      Activation of J774 cells with collagen-activated nuclear factor-kappaB, p38
      mitogen-activated protein kinase (MAPK), and c-jun N-terminal kinase (JNK) and a
      pharmacological inhibitor of each signaling molecule significantly reduced
      collagen-induced NO production. Thus, we have demonstrated, for the first time,
      that the interaction of DDR1 with collagen induces iNOS expression and subsequent
      NO synthesis in J774 cells through activation of NF-kappaB, p38 MAPK, and JNK and
      suggest that intervention of DDR1 signaling in macrophages may be useful in
      controlling inflammatory diseases in which NO plays a critical role.

PMID- 17210448
TI  - Hepatic oxidative DNA damage correlates with iron overload in chronic hepatitis C
      patients.
AB  - Hepatic oxidative stress occurs in chronic hepatitis C (CH-C), but little is
      known about its producing mechanisms and precise role in the pathogenesis of the
      disease. To determine the relevance of hepatic oxidatively generated DNA damage
      in CH-C, 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts were quantified in liver
      biopsy specimens by immunohistochemical staining, and its relationship with
      clinical, biochemical, and histological parameters, and treatment response was
      assessed in 40 CH-C patients. Hepatic 8-OHdG counts were significantly correlated
      with serum transaminase levels (r=0.560, p=0.0005) and histological grading
      activity (p=0.0013). Remarkably, 8-OHdG levels were also significantly related to
      body and hepatic iron storage markers (vs serum ferritin, r=0.565, p=0.0004; vs
      hepatic total iron score, r=0.403, p=0.0119; vs hepatic hepcidin messenger RNA,
      r=0.516, p=0.0013). Baseline hepatic oxidative stress was more prominent in
      nonsustained virological responder (non-SVR) than in SVR to interferon
      (IFN)/ribavirin treatment (50.8 vs 32.7 cells/10(5) microm2, p=0.0086). After
      phlebotomy, hepatic 8-OHdG levels were significantly reduced from 53.4 to 21.1
      cells/10(5) microm2 (p=0.0125) with concomitant reductions of serum transaminase
      and iron-related markers in CH-C patients. In conclusion, this study showed that
      hepatic oxidatively generated DNA damage frequently occurs and is strongly
      associated with increased iron deposition and hepatic inflammation in CH-C
      patients, suggesting that iron overload is an important mediator of hepatic
      oxidative stress and disease progression in chronic HCV infection.

PMID- 17210449
TI  - Selective protection of nuclear thioredoxin-1 and glutathione redox systems
      against oxidation during glucose and glutamine deficiency in human colonic
      epithelial cells.
AB  - Little is known about the relative sensitivities of antioxidant systems in
      nuclei, mitochondria, and cytoplasm. The present study examined the oxidation of
      the thiol-dependent antioxidant systems in these subcellular compartments under
      conditions of limited energy supply of human colonic epithelial HT-29 cells
      induced by depletion of glucose (Glc) and glutamine (Gln) from the culture
      medium. Increased oxidation of dichlorofluoroscein (DCF) indicated an increased
      level of reactive oxygen species (ROS). Redox Western blot analysis showed
      oxidation of cytosolic thioredoxin-1 (Trx1) and mitochondrial thioredoxin-2
      (Trx2) by 24 h, but little oxidation of nuclear Trx1. The Trx1 substrate, redox
      factor-1 (Ref-1), was also oxidized in cytosol but was reduced in nuclei. Protein
      S-glutathionylation (PrSSG), expressed as a ratio of protein thiol (PrSH), was
      also increased in the cytosol, while nuclear PrSSG/PrSH was not. Taken together,
      the data show that oxidative stress induced by depletion of Glc and Gln affects
      the redox states of proteins in the cytoplasm and mitochondria more than those in
      the nucleus. These results indicate that the nuclear compartment has better
      protection against oxidative stress than cytoplasm or mitochondria. These results
      further suggest that energy and/or substrate supply may contribute to sensitivity
      of mitochondrial and cytoplasmic systems to oxidative damage.

PMID- 17210450
TI  - Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger
      protection by cotreatment of acetyl-L-carnitine and alpha-lipoic acid against HNE
      mediated oxidative stress and neurotoxicity: implications for Alzheimer's
      disease.
AB  - Oxidative stress has been shown to underlie neuropathological aspects of
      Alzheimer's disease (AD). 4-Hydroxy-2-nonenal (HNE) is a highly reactive product
      of lipid peroxidation of unsaturated lipids. HNE-induced oxidative toxicity is a
      well-described model of oxidative stress-induced neurodegeneration. GSH plays a
      key role in antioxidant defense, and HNE exposure causes an initial depletion of
      GSH that leads to gradual toxic accumulation of reactive oxygen species. In the
      current study, we investigated whether pretreatment of cortical neurons with
      acetyl-L-carnitine (ALCAR) and alpha-lipoic acid (LA) plays a protective role in
      cortical neuronal cells against HNE-mediated oxidative stress and neurotoxicity.
      Decreased cell survival of neurons treated with HNE correlated with increased
      protein oxidation (protein carbonyl, 3-nitrotyrosine) and lipid peroxidation
      (HNE) accumulation. Pretreatment of primary cortical neuronal cultures with ALCAR
      and LA significantly attenuated HNE-induced cytotoxicity, protein oxidation,
      lipid peroxidation, and apoptosis in a dose-dependent manner. Additionally,
      pretreatment of ALCAR and LA also led to elevated cellular GSH and heat shock
      protein (HSP) levels compared to untreated control cells. We have also determined
      that pretreatment of neurons with ALCAR and LA leads to the activation of
      phosphoinositol-3 kinase (PI3K), PKG, and ERK1/2 pathways, which play essential
      roles in neuronal cell survival. Thus, this study demonstrates a cross talk among
      the PI3K, PKG, and ERK1/2 pathways in cortical neuronal cultures that contributes
      to ALCAR and LA-mediated prosurvival signaling mechanisms. This evidence supports
      the pharmacological potential of cotreatment of ALCAR and LA in the management of
      neurodegenerative disorders associated with HNE-induced oxidative stress and
      neurotoxicity, including AD.

PMID- 17210451
TI  - Accumulation of oxidatively generated DNA damage in the brain: a mechanism of
      neurotoxicity.
AB  - Unrepaired or erroneously repaired DNA lesions drive genomic instability and
      contribute to cellular and organ decline. Since delayed neuropathologies are
      common in survivors of smoke inhalation injuries, we asked whether the integrity
      of brain DNA might be compromised by acute exposure to combustion smoke. Although
      many studies demonstrate that the brain is equipped to repair oxidatively damaged
      DNA, to date, the capacity for accurate DNA repair under conditions of disrupted
      oxygenation and oxidative stress has not been defined. We show that DNA adducts
      detectable by their ability to block PCR amplification form in the rat
      hippocampus after acute exposure to smoke. To identify the different types of
      adducts and to dissect their temporal formation and repair profiles in vivo in
      the brain, we used DNA-modifying enzymes to convert specific adducts into strand
      breaks prior to PCR amplification. Using this strategy, we detected formation of
      oxidative DNA adducts early on after smoke inhalation, while mismatched bases
      emerged at the later recovery times, potentially due to an erroneous DNA repair
      process. Erroneous repair can be mutagenic and because the initial smoke-induced
      oxidative damage to DNA is extensive, compromised fidelity of DNA repair may
      underlie neurotoxicity and contribute to delayed death of hippocampal neurons.

PMID- 17210452
TI  - Role of peroxynitrite in endothelial damage mediated by Cyclosporine A.
AB  - Although Cyclosporine A (CsA) is an effective therapy for immunosuppression, its
      use encompasses serious side effects that have been associated with oxidative
      stress. We previously reported the intracellular formation of both peroxynitrite
      and 3-nitrotyrosine in cultured bovine aortic endothelial cells (BAEC) when
      exposed to CsA. Here we show that re-addition of CsA to BAEC increases
      peroxynitrite formation in a concentration-dependent manner. This effect is
      inhibited by the glutathione donor and antioxidant, N-acetylcysteine (NAC). BAEC
      exposed to CsA showed impaired integrity of plasma membranes and increased
      cytolysis, a phenomenon prevented by NAC. When CsA was administered to mice, the
      increased presence of 3-nitrotyrosine was detected in the aortic endothelium, an
      effect also abrogated by the concomitant administration of NAC. An increase in
      nitrated MnSOD was detected in BAEC treated with CsA and the peroxynitrite donor
      SIN-1 and recapitulated in recombinant MnSOD, exposed to the conditioned media
      from BAEC. We propose that CsA promotes nitration of specific molecular targets,
      such as MnSOD, within vascular endothelial cells. This may represent a
      pathogenetic mechanism of vascular injury. Inhibition of this process by
      clinically applicable antioxidants, such as NAC, lends a basis for the
      exploration of therapeutic alternatives in patients treated with CsA.

PMID- 17210454
TI  - Improving the in vivo predictability of an on-line HPLC stable free radical
      decoloration assay for antioxidant activity in methanol-buffer medium.
AB  - The pivotal role of ROS (reactive oxygen species) in various (patho)physiological
      processes has stimulated research on the potential of intervening in these
      processes with antioxidants (AO). In vitro model systems to investigate AO
      activity against the various ROS are a valuable tool in classifying antioxidants.
      To improve the in vivo predictability of the results obtained, we have modified
      and characterized the widely used DPPH (2,2'-diphenyl-1-picrylhydrazyl) on-line
      decoloration assay. Previous investigations using the DPPH reaction in a pure
      methanolic medium exhibit slow kinetics and a reaction going to completion. In
      this study, a medium which includes an aqueous buffer at physiological pH has
      been applied, resulting in the rapid establishment of equilibrium. The results
      obtained in an aqueous medium at physiological pH are expected to be more
      relevant for extrapolation to in vivo circumstances than previously published
      findings. The antioxidants investigated are classified according to the results
      obtained and the relevance of their behavior to in vivo situations is discussed.
      Special emphasis is put on the significance of the results for prediction of
      redox-cycling characteristics and structure-activity relationships.

PMID- 17210453
TI  - Reversible reduction of nitroxides to hydroxylamines: roles for ascorbate and
      glutathione.
AB  - Biological applications of stable nitroxyl radicals, NR, include their use as
      contrast agents for magnetic resonance imaging, spin labels, superoxide dismutase
      mimics, and antioxidants. The rapid reduction of NR in biological samples into
      hydroxylamines (HA) significantly limits their application. In turn, reoxidation
      of HA back to the NR has been used for detection of reactive oxygen species
      (ROS). In this work comparative studies of the reduction of pyrrolidine,
      imidazoline, and imidazolidine NR by ascorbate were performed taking advantage of
      recently synthesized tetraethyl-substituted NR with much higher stability toward
      reduction both in vitro and in vivo. Surprisingly, these NR kept 10-50% of
      initial intensity of electron paramagnetic resonance signal for about 1 h in the
      presence of 100-fold excess of ascorbate. To explain these data, reoxidation of
      the corresponding HA by ascorbate radical and dehydroascorbic acid back to the NR
      was proposed. This hypothesis was supported by direct measurement of the NR
      appearance from the HA on ascorbate radical generation by ascorbate oxidase, or
      in the presence of the dehydroascorbic acid. The reversible reaction between NR
      and ascorbate was observed for the various types of NR, and the rate constants
      for direct and reverse reactions were determined. The equilibrium constants for
      one-electron reduction of the tetraethyl-substituted NR by ascorbate were found
      to be in the range from 2.65x10(-6) to 10(-5) which is significantly lower than
      corresponding values for the tetramethyl-substituted NR (more or about 10(-4)).
      This explains the establishment of an EPR-detectable quasi-equilibrium level of
      tetraethyl-substituted NR in the presence of an excess of ascorbate. The redox
      reactions of the NR-HA couple in ascorbate-containing media were found to be
      significantly affected by glutathione (GSH). This effect was attributed to the
      reduction of ascorbate radicals by GSH, and the rate constant of this reaction
      was found to be equal to 10 M-1 s-1. In summary, the data provide new insight
      into the redox chemistry of NR and HA, and significantly affect interpretation
      and strategy of their use as redox- and ROS-sensitive probes, or as antioxidants.

PMID- 17210456
TI  - Postmeeting summary on the round table discussion at the Seventh International
      Symposium on Technetium in Chemistry and Nuclear Medicine held in Bressanone,
      Italy on Sept 6-9, 2006.

PMID- 17210455
TI  - PrxQ-A, a member of the peroxiredoxin Q family, plays a major role in defense
      against oxidative stress in the cyanobacterium Anabaena sp. strain PCC7120.
AB  - The genome of the cyanobacterium Anabaena PCC 7120 encodes seven polypeptides
      showing sequence similarities with peroxiredoxins (Prx-s). One of them, prxQ-A
      (alr2503), which encodes a Prx Q homologue, is located in the same gene cluster
      as pkn22, which encodes a Ser/Thr kinase. Here we report that the pkn22-knockout
      mutant (Mp22) is sensitive to oxidative stress because it fails to synthesize
      PrxQ-A; the expression of prxQ-A is significantly induced under oxidative stress
      conditions. The hypersensitivity of the Mp22 mutant to oxidative stress was
      restored by inducing the expression of the prxQ-A gene in trans. The recombinant
      PrxQ-A protein shows antioxidant activity protecting the DNA from being degraded
      by reactive oxygen species, catalyzes the reduction of H2O2 in the presence of
      DTT, and shows thioredoxin-dependent peroxidase activity in vitro. The conserved
      Cys47 residue is the peroxide oxidation site, since the replacement of Cys47 by a
      Ser residue completely abolished the peroxidase activity. All these data suggest
      that PrxQ-A may efficiently protect this organism from oxidative stress.

PMID- 17210457
TI  - Labeling of low-density lipoproteins using the 18F-labeled thiol-reactive reagent
      N-[6-(4-[18F]fluorobenzylidene)aminooxyhexyl]maleimide.
AB  - The novel thiol-group-selective bifunctional 18F-labeling agent N-[6-(4
      [18F]fluoro-benzylidene)aminooxyhexyl]maleimide ([18F]FBAM) has been developed.
      The bifunctional labeling precursor N-(6-aminoxyhexyl)maleimide containing a
      thiol-reactive maleimide group and a carbonyl-group-reactive aminooxy group was
      prepared in only three steps in a total chemical yield of 59%. Subsequent
      radiolabeling with 4-[18F]fluorobenzaldehyde gave the bifunctional 18F-labeling
      agent [18F]FBAM in a radiochemical yield of 29%. In a typical experiment, 3.88
      GBq of [18F]fluoride could be converted into 723 MBq of [18F]FBAM within 69 min.
      Conjugation of [18F]FBAM with thiol groups was exemplified with the cysteine
      containing tripeptide glutathione and with various apolipoproteins of human low
      density lipoprotein (LDL) subfractions. The latter was evaluated with respect to
      the uptake of [18F]FBAM-LDL subfractions in human hepatoma cells (HepG2) in
      vitro. In vivo biodistribution studies in rats revealed high stability for
      [18F]FBAM-LDL subfractions. Moreover, the metabolic fate of [18F]FBAM-LDL
      subfractions in vivo was delineated by dynamic positron emission tomography
      studies using a dedicated small animal tomograph. Data were compared to former
      studies that used the NH2-reactive 18F-labeling agent N-succinimidyl-4
      [18F]fluorobenzoate. The compound [18F]FBAM can be considered as an excellent
      prosthetic group for the selective and mild 18F labeling of thiol-group
      containing biomolecules suitable for subsequent investigations in vitro and in
      vivo.

PMID- 17210458
TI  - Chemical and biological characterization of new Re(CO)3/[99mTc](CO)3 bombesin
      analogues.
AB  - INTRODUCTION: Bombesin, a neuropeptide with potential for breast and prostate
      tumor targeting, is rapidly metabolized in vivo, and as a result, uptake in tumor
      xenografts in mice is poor. An improvement can be expected from the introduction
      of nonnatural amino acids and spacers. Leu13 was replaced by cyclohexylalanine
      and Met14 by norleucine. Two spacers, -betaAla-betaAla- and 3,6-dioxa-8
      aminooctanoic acid, were inserted between the receptor-binding amino acid
      sequence (7-14) of bombesin (BBS) and the retroN(alpha)-carboxymethyl histidine
      chelator used for labeling with the [99mTc](CO)3 core and the rhenium (Re)
      congener. METHODS: The biological characterization of the new compounds was
      performed both in vitro on prostate carcinoma PC-3 cells (binding affinity,
      internalization/externalization) and in vivo (biodistribution in nude mice with
      tumor xenografts). The stability was also investigated in human plasma. The Re
      analogues were prepared for chemical characterization. RESULTS: The nonnatural
      amino acids led to markedly slower degradation in human plasma and PC-3 cell
      cultures. The receptor affinity of the new technetium 99m ([99mTc])-labeled BBS
      analogues was similar to the unmodified compound with Kd<1 nM. Uptake in the
      pancreas and in PC-3 tumor xenografts in nude mice was blocked by unlabeled BBS.
      The best target-to-nontarget uptake ratio was clearly due to the presence of the
      more polar spacer, -betaAla-betaAla-. CONCLUSIONS: The different spacers did not
      have a significant effect on stability or receptor affinity but had a clear
      influence on the uptake in healthy organs and tumors. Uptake in the kidneys was
      lower than in the liver, which is likely to be due to the lipophilicity of the
      compounds. A specific, high uptake was also observed in the gastrin-releasing
      peptide receptor-rich pancreas. Thus, with the introduction of spacers the in
      vivo properties of the compounds can be improved while leaving the affinity
      unaffected.

PMID- 17210459
TI  - Effects of linker variation on the in vitro and in vivo characteristics of an
      111In-labeled RGD peptide.
AB  - INTRODUCTION: Due to the selective expression of the alpha(v)beta3 integrin in
      tumors, radiolabeled arginine-glycine-aspartic acid (RGD) peptides are attractive
      candidates for tumor targeting. Minor modifications of these peptides could have
      a major impact on in vivo characteristics. In this study, we systematically
      investigated the effects of linker modification between two cyclic RGD sequences
      and DOTA (1,4,7,10-tetraazadodecane-N,N',N",N'''-tetraacetic acid) on the in
      vitro and in vivo characteristics of the tracer. METHODS: A dimeric RGD peptide
      was synthesized and conjugated either directly with DOTA or via different
      linkers: PEG4 (polyethylene glycol), glutamic acid or lysine. The RGD peptides
      were radiolabeled with 111In, and their in vitro and in vivo alpha(v)beta3
      binding characteristics were determined. RESULTS: LogP values varied between 
      2.82+/-0.06 and -3.95+/-0.33. The IC50 values for DOTA-E-[c(RGDfK)]2, DOTA-PEG4-E
      [c(RGDfK)]2, DOTA-E-E-[c(RGDfK)]2 and DOTA-K-E-[c(RGDfK)]2 were comparable. Two
      hours after injection, the tumor uptakes of the 111In-labeled compounds were not
      significantly different. The kidney accumulation of [111In]-DOTA-K-E-[c(RGDfK)]2
      [4.05+/-0.20% of the injected dose per gram (ID/g)] was significantly higher as
      compared with that of [111In]-DOTA-E-[c(RGDfK)]2 (2.63+/-0.19% ID/g; P<.05) as
      well as that of [111In]-DOTA-E-E-[c(RGDfK)]2 (2.16+/-0.21% ID/g; P<.01). The
      liver uptake of [111In]-DOTA-E-E-[c(RGDfK)]2 (2.12+/-0.09% ID/g) was
      significantly higher as compared with that of [111In]-DOTA-E-[c(RGDfK)]2 (1.64+/
      0.1% ID/g; P<.05) as well as that of [111In]-DOTA-K-E-[c(RGDfK)]2 (1.52+/-0.04%
      ID/g; P<.01). CONCLUSIONS: Linker variation did not affect affinity for
      alpha(v)beta3 and tumor uptake. Insertion of lysine caused enhanced kidney
      retention; that of glutamic acid also resulted in enhanced retention in the
      kidneys. PEG4 appeared to be the most suitable linker as compared with glutamic
      acid and lysine because it has the highest tumor-to-blood ratio and the lowest
      uptake in the kidney and liver.

PMID- 17210460
TI  - Cellular penetration and nuclear importation properties of 111In-labeled and 123I
      labeled HIV-1 tat peptide immunoconjugates in BT-474 human breast cancer cells.
AB  - INTRODUCTION: Our objective was to compare the cell penetration and nuclear
      importation properties of 111In-labeled and 123I-labeled immunoconjugates (ICs)
      composed of 16-mer peptides (GRKKRRQRRRPPQGYG) derived from HIV-1 transactivator
      of transcription (tat) protein and anti-mouse IgG (mIgG) in BT-474 breast cancer
      (BC) cells. METHODS: [111In]tat ICs were constructed by site-specific conjugation
      of tat peptides to NaIO4(-)-oxidized carbohydrates in the Fc domain of
      diethylenetriaminepentaacetic-acid-modified anti-mIgG antibodies.
      Immunoreactivity against mIgG was assessed in a competition assay. The kinetics
      of the accumulation of [111In]anti-mIgG-tat IC and [123I]anti-mIgG-tat ICs in BT
      474 cells and the elimination of radioactivity from cells, cytoplasm or nuclei
      were determined. The effects of excess tat peptides or NH4Cl (an inhibitor of
      endosomal acidification) on cellular uptake and nuclear importation of
      [111In]anti-mIgG-tat were measured. RESULTS: [111In]anti-mIgG-tat was >97%
      radiochemically pure and exhibited preserved immunoreactivity with mIgG epitopes.
      [123I]Anti-mIgG-tat penetrated BT-474 cells more rapidly than [111In]anti-mIgG
      tat ICs and achieved a 1.5-fold to a 2-fold higher uptake in cells and nuclei.
      Cell penetration and nuclear uptake of [111In]anti-mIgG-tat were inhibited by
      excess tat peptides and NH4Cl. Elimination of radioactivity from BT-474 cells and
      nuclei was more rapid and complete for 123I-labeled than for 111In-labeled anti
      mIgG-tat ICs. CONCLUSION: Tat peptides derived from HIV-1 tat protein promoted
      the penetration and nuclear uptake of radioactivity following the incubation of
      111In-labeled and 123I-labeled anti-mIgG antibodies with BT-474 human BC cells.
      111In-labeled tat ICs are feasible for inserting radionuclides into cancer cells
      with potential for targeting intracellular and, particularly, nuclear epitopes
      for imaging and/or radiotherapeutic applications.

PMID- 17210461
TI  - Nonspecific cellular accumulation of 99mTc-labeled oligonucleotides in culture is
      influenced by their guanine content.
AB  - Specific accumulation of radiolabeled antisense oligonucleotides as a result of
      binding by an antisense mechanism to target mRNAs in tumor has been repeatedly
      observed. However, the mechanisms responsible for nonspecific cellular
      accumulation remain almost completely unexplored. We have occasionally observed
      in cell culture nonspecific accumulations of 99mTc-labeled sense, scrambled or
      random control oligonucleotides in tumor cells comparable to or even higher than
      those of the corresponding antisense oligonucleotides. We have also observed that
      these nonspecific accumulations of control oligonucleotides are sequence
      dependent. To explore the influence of base composition on nonspecific
      accumulation, we used MCF-7 breast cancer cells, along with 10 uniform
      phosphorothioates and 5 uniform phosphodiesters oligonucleotides. Three of the
      phosphorothioates were antisense against different sites within the survivin
      mRNA, and two were the corresponding sense and scrambled controls. In addition,
      the accumulations in MCF-7 cells of radiolabeled poly A, poly C, poly T and poly
      GGGA phosphorothioate oligonucleotides were also studied to explore the influence
      of each nitrogenous base on the nonspecific cell accumulations of
      phosphorothioate oligonucleotides. Our results show that guanine content is an
      important determinant of nonspecific cellular accumulations under the conditions
      of this investigation. If this observation can be shown to be universally
      applicable to other cell types, then the selection of control sequences in
      studies of antisense tumor targeting should avoid those that are guanine rich, if
      possible.

PMID- 17210463
TI  - In vivo selective binding of (R)-[11C]rolipram to phosphodiesterase-4 provides
      the basis for studying intracellular cAMP signaling in the myocardium and other
      peripheral tissues.
AB  - INTRODUCTION: Phosphodiesterase-4 (PDE4) enzymes specifically break down the
      second messenger cAMP, thereby terminating the intracellular signaling cascade
      that plays an essential role in neurohormonal modulation of many physiological
      systems. PDE4 activity and expression are regulated by cAMP levels, suggesting
      that measurement of PDE4 provides an index of intracellular cAMP signaling.
      METHODS: Male Sprague-Dawley rats were administered (R)- or the less active
      enantiomer (S)-[11C]rolipram and sacrificed 30 min later with tracer retention
      measured in various tissues. Co-injections with saturating doses of unlabeled (R)
      rolipram, (S)-rolipram and Ro 20-1724, as well as subtype-selective PDE
      inhibitors vinpocetine, Bay 60-7550, cilostazol and zaprinast were used to
      establish binding selectivity for PDE4 over PDE1, PDE2, PDE3 and PDE5 subtypes,
      respectively. Autoradiography was performed to substantiate results of
      biodistribution studies in the myocardium. RESULTS: In vivo (R)-[11C]rolipram
      retention was dose-dependently reduced by co-injections of (R)-rolipram and (S)
      rolipram (ED50 values of 0.03 mg/kg and 0.2 mg/kg, respectively). Vinpocetine,
      Bay 60-7550, cilostazol and zaprinast had no effect on (R)-[11C]rolipram binding,
      while (R)-rolipram and Ro 20-1724 reduced the tracer uptake to nonspecific levels
      in PDE4-rich tissues. CONCLUSIONS: In addition to the brain, (R)-[11C]rolipram
      binds selectively to PDE4 across all cardiac regions, skeletal muscle, lungs and
      pancreas, but not in the adipose tissues. In vivo findings were confirmed by in
      vitro autoradiography studies, suggesting that (R)-[11C]rolipram can be applied
      to evaluate alterations in central and peripheral PDE4 levels and cAMP-mediated
      signaling.

PMID- 17210462
TI  - Evaluation of radiolabeled ML04, a putative irreversible inhibitor of epidermal
      growth factor receptor, as a bioprobe for PET imaging of EGFR-overexpressing
      tumors.
AB  - Overexpression of epidermal growth factor receptor (EGFR) has been implicated in
      tumor development and malignancy. Evaluating the degree of EGFR expression in
      tumors could aid in identifying patients for EGFR-targeted therapies and in
      monitoring treatment. Nevertheless, no currently available assay can reliably
      quantify receptor content in tumors. Radiolabeled inhibitors of EGFR-TK could be
      developed as bioprobes for positron emission tomography imaging. Such imaging
      agents would not only provide a noninvasive quantitative measurement of EGFR
      content in tumors but also serve as radionuclide carriers for targeted
      radiotherapy. The potency, reversibility, selectivity and specific binding
      characteristics of ML04, an alleged irreversible inhibitor of EGFR, were
      established in vitro. The distribution of the F-18-labeled compound and the
      extent of EGFR-specific tumor uptake were evaluated in tumor-bearing mice. ML04
      demonstrated potent, irreversible and selective inhibition of EGFR, combined with
      specific binding to the receptor in intact cells. In vivo distribution of the
      radiolabeled compound revealed tumor/blood and tumor/muscle activity uptake
      ratios of about 7 and 5, respectively, 3 h following administration of a
      radiotracer. Nevertheless, only minor EGFR-specific uptake of the compound was
      detected in these studies, using either EGFR-negative tumors or blocking studies
      as controls. To improve the in vivo performance of ML04, administration via
      prolonged intravenous infusion is proposed. Detailed pharmacokinetic
      characterization of this bioprobe could assist in the development of a kinetic
      model that would afford accurate measurement of EGFR content in tumors.

PMID- 17210464
TI  - Assessment of 186Re chelate-conjugated bisphosphonate for the development of new
      radiopharmaceuticals for bones.
AB  - INTRODUCTION: The preferable pharmacokinetics of rhenium-186 (186Re)
      monoaminemonoamidedithiol-conjugated or 186Re-mercaptoacetyltriglycine-conjugated
      bisphosphonates (BPs) suggested that the molecular design would be applicable to
      other radionuclides such as 68Ga, 99mTc, 153Sm and 177Lu. In this study, a key
      factor affecting the pharmacokinetics of a chelate-conjugated BP was investigated
      to estimate the validity and the applicability of molecular design. METHODS:
      Chemically inert and well-characterized
      tricarbonyl[186Re][(cyclopentadienylcarbonyl amino)-acetic acid]rhenium
      ([186Re]CpTR-Gly) was conjugated with 3-amino-1-hydroxypropylidene-1,1
      bisphosphonate and purified by high-performance liquid chromatography (HPLC) to
      prepare [186Re](1-{3-[tricarbonyl(cyclopentadienylcarbonyl amino)-acetylamido]-1
      hydroxy-1-phosphono-propyl}-phosphonic acid)rhenium ([186Re]CpTR-Gly-APD). Plasma
      stability, plasma protein binding, hydroxyapatite (HA) binding and the
      pharmacokinetics of [186Re]CpTR-Gly-APD were compared with those of 186Re 1
      hydroxyethylidene-1,1-diphosphonate (HEDP). The effect of HEDP coadministration
      and preadministration on the pharmacokinetics of [186Re]CpTR-Gly-APD was also
      determined. RESULTS: The HPLC-purified [186Re]CpTR-Gly-APD showed higher plasma
      stability, higher HA binding, higher bone accumulation and lower plasma protein
      binding than did 186Re-HEDP. However, HA binding of [186Re]CpTR-Gly-APD decreased
      to levels slightly higher than that of 186Re-HEDP at similar HEDP concentrations.
      Bone accumulation of [186Re]CpTR-Gly-APD also decreased to levels similar to that
      of 186Re-HEDP when [186Re]CpTR-Gly-APD was coinjected with HEDP equivalent to
      that in 186Re-HEDP. In contrast, HEDP pretreatment did not impair bone
      accumulation of the two 186Re-labeled compounds. However, a delay in blood
      clearance and an increase in renal radioactivity levels were observed
      particularly with 186Re-HEDP. CONCLUSIONS: Although 186Re-HEDP possessed HA
      binding and bone accumulation similar to those of [186Re]CpTR-Gly-APD, the
      specific activity of 186Re-labeled BPs was found to play a crucial role in bone
      accumulation and blood clearance. Thus, the molecular design of chelate
      conjugated BP would be useful for the development of bone-seeking
      radiopharmaceuticals with a variety of radionuclides by selecting chelating
      molecules that provide high specific activities.

PMID- 17210465
TI  - 18F-labeled styrylpyridines as PET agents for amyloid plaque imaging.
AB  - Positron emission tomography (PET) imaging of beta-amyloid (Abeta) plaques in the
      brain is a potentially valuable tool for studying the pathophysiology of
      Alzheimer's disease (AD). It may also be applicable for measuring the
      effectiveness of therapeutic drugs aimed at lowering Abeta plaques in the brain.
      We have successfully reported a series of 18F-labeled fluoropegylated stilbenes
      for PET imaging studies. Encouraging results clearly demonstrated the usefulness
      of 18F-labeled stilbenes as potential Abeta plaque-imaging agents. In the present
      study, we applied a similar approach to a styrylpyridine backbone structure.
      Among all derivatives examined, (E)-2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)-5-(4
      dimethylaminostyryl)-pyridine (2) displayed high binding affinity in postmortem
      AD brain homogenates (Ki=2.5+/-0.4 nM, with [125I]IMPY as radioligand). No
      carrier-added [18F]2 was successfully prepared by [18F]fluoride displacement of
      the corresponding tosylate precursor with a high labeling yield (30-40%) and a
      high radiochemical purity (>99%). Specific activity at the end of synthesis was
      determined to be 1500-2000 Ci/mmol. The tracer [18F]2 showed adequate
      lipophilicity (log P=3.22). In vivo biodistribution of [18F]2 in normal mice
      exhibited excellent initial brain penetration and rapid washout (7.77% and 1.03%
      dose/g in the brain at 2 and 30 min after intravenous injection, respectively)-
      properties that are highly desirable for Abeta-plaque-specific brain imaging
      agents. Autoradiography of AD brain sections and homogenate binding with
      postmortem AD brain tissues confirmed the high binding signal of [18F]2 due to
      the presence of Abeta plaques. These preliminary results suggest that novel PET
      tracers may be potentially useful for the imaging of Abeta plaques in the living
      human brain.

PMID- 17210466
TI  - Validation of 8-[123I]iodo-L-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3
      carboxylic acid as an imaging agent for prostate cancer in experimental models of
      human prostate cancer.
AB  - INTRODUCTION: Very few tracers are currently available for the detection and
      staging of prostate cancer with positron emission tomography and single-photon
      emission computed tomography. This study evaluates the potential of 8-[123I]iodo
      1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid [ITIC(OH)] as an
      imaging agent for prostate cancer in experimental models of human prostate
      cancer. METHODS: ITIC(OH) was prepared by the IODO-GEN method, with 82+/-7%
      radiochemical yield and >99% radiochemical purity after high-performance liquid
      chromatography. Thereafter, ITIC(OH) was examined in CD-1 nu/nu mice engrafted
      with human PC-3 and DU-145 prostate cancer in the flank or orthotopically in the
      prostate. Bioevaluation involved examination of the in vivo stability and uptake
      characteristics of ITIC(OH) into tumors and different organs by dynamic in vivo
      analysis and gamma counting of organs of interest after dissection. RESULTS:
      ITIC(OH) showed good in vivo stability for biological investigations and was
      primary cleared through urine. In vivo, ITIC(OH) accumulated highly and
      specifically in tumors, reaching 13.6+/-2.1% to 16.2+/-2.5% injected dose per
      gram (ID/g) in heterotopic tumors compared with 14.8+/-2.6% and 17.6+/-3.4% ID/g
      in orthotopic tumor engrafts at 60 and 240 min postinjection, respectively. In
      contrast, radioactivity uptake in the blood, spleen, liver and gastrointestinal
      tract was moderate and decreased with time, resulting in marked tumor-to
      background and excellent visualization of tumors. CONCLUSION: These results
      suggest that ITIC(OH) is a promising candidate as radiotracer for detecting
      prostate cancer and warrants further studies in patients to ascertain its
      potential as an imaging agent for clinical use.

PMID- 17210467
TI  - Mitochondrial avid radioprobes. Preparation and evaluation of 7'(Z)
      [125I]iodorotenone and 7'(Z)-[125I]iodorotenol.
AB  - The loss of mitochondrial function has been implicated in a number of maladies
      such as Huntington's disease, Parkinson's disease (PD), cancer and cardiovascular
      disease. The objective of this research was to develop a radiolabeled
      mitochondrial probe. Two tracers, 7'-Z-iodorotenol and 7'-Z-iodorotenone, analogs
      of rotenone a natural product that inhibits Complex I of the mitochondrial
      electron transport chain, have been labeled with iodine-125 in 45-85% yield in a
      single step from the corresponding tributylstannyl precursor. In vivo
      distribution in adult male Sprague-Dawley rats for both compounds showed high
      accumulation in the heart (1.7-3.7 %ID/g at 1 h), a tissue with high
      mitochondrial content. Z-Iodorotenol did not washout of most tissues between 1
      and 2 h postinjection, whereas Z-iodorotenone showed moderate washout (7-26%)
      over the same period. By 24 h, there was significant loss of both compounds from
      most tissues including the heart. Heart-to-blood, -lung and -liver ratios for Z
      iodorotenone of 28.9, 10.7 and 2.4, respectively, were two- to fourfold higher
      than the Z-iodorotenol ratios. Compared to the current clinical perfusion
      tracers, 99mTc-sestamibi and 99mTc-tetrofosmin, Z-iodorotenone demonstrates
      similar 1 h heart accumulation and significantly higher heart-to-lung ratio
      (P<.001). Z-Iodorotenone heart-to-liver ratio is equivalent to 99mTc-sestamibi.
      7'-Z-Iodorotenone possesses distribution characteristics of an improved tracer
      for SPECT perfusion studies.

PMID- 17210468
TI  - Design and evaluation of the tandem target for a simultaneous production of
      [11C]CH4 and [18F]-fluoride.
AB  - The tandem target for a simultaneous production of [11C]CH4 and [(18)F]-fluoride
      has been designed and evaluated. A separate recovery system has been applied for
      a simultaneous collection of [11C]CH4 and [(18)F]-fluoride after a bombardment.
      The [11C]CH4 target was placed in front, and the [18F]-fluoride target was posted
      successively. An aluminum grid was employed between the two target cavities to
      improve the burst pressure of the titanium foil during an irradiation. It was
      demonstrated that a useful amount of [11C]CH4 and [18F]-fluoride can be produced
      simultaneously by this newly designed system.

PMID- 17210469
TI  - Infrared-based module for the synthesis of 68Ga-labeled radiotracers.
AB  - INTRODUCTION: Generator-produced positron emission tomography tracers have gained
      much attention recently due to favorable imaging characteristics, accessibility
      and affordability. The focus of this study was to design and validate a
      semiautomated module for 68Ga-labeled chemistry utilizing infrared-based heating
      for rapid control of thermal cycle. METHODS: A prototype module was built and
      installed in our laboratory. DOTA (1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetra
      acetic acid) was manually labeled (10-1000 nmol) with 68Ga to optimize synthesis
      conditions. For automation, 250 nmol of DOTA was labeled with 68Ga with reaction
      times of 5 min (n=5), 10 min (n=5) and 20 min (n=6). A dose calibrator and radio
      thin-layer chromatography were used to access the product yield and quality of
      both manual and automated syntheses. RESULTS: A semiautomated 68Ga synthesis
      module was developed. The system showed that software control could be used to
      drive a multistep radiochemical synthesis and to produce 68Ga-DOTA with >95%
      radiochemical purity, similar to that in manual synthesis. The device also showed
      that for a short reaction time of 5 min, decay-corrected radioactive yields of
      >70% could be achieved. The total synthesis was as short as 22 min, including 6-8
      min for HCl evaporation. The temperature and pressure profiles of the process
      were consistent. CONCLUSION: We demonstrated the use of a commercially available
      68Ga/68Ge generator with a semiautomated module to successfully label the
      bifunctional chelator DOTA with 68Ga. Further investigation with different 68Ga
      labeled bioconjugates is warranted to demonstrate the usefulness of the module as
      a tool for tracer development and imaging research.

PMID- 17210470
TI  - Alterations in myocardial characteristics associated with obesity: detection,
      mechanisms, and implications.
AB  - Hypertension, obstructive sleep apnea, and coronary artery disease all contribute
      to the myocardial dysfunction in obesity. However, the development of sensitive
      cardiac imaging techniques has enabled detection of myocardial structural and
      functional changes independently attributable to obesity, at the preclinical
      stage. This review will evaluate the evidence for myocardial disease in this
      setting, its significance, important mechanisms, preclinical detection, and
      possible therapeutic implications.

PMID- 17210471
TI  - Activated alphavbeta3 integrin targeting in injury-induced vascular remodeling.
AB  - There is currently no imaging modality to track the remodeling process, a common
      feature of a broad spectrum of vasculopathies, in vivo. alphavbeta3 Integrin is
      up-regulated in proliferating vascular cells. RP748, a novel peptidomimetic
      tracer, binds specifically to the activated alphavbeta3 conformer and exhibits
      favorable binding characteristics for in vivo imaging. In a model of injury
      induced vascular remodeling in apoE null mice, RP748 localization to the injured
      carotid arteries parallels vascular cell proliferation, providing an opportunity
      to image the remodeling process in vivo.

PMID- 17210472
TI  - Oral brain natriuretic peptide: a novel strategy for chronic protein therapy for
      cardiovascular disease.
AB  - In 1956, secretory granules were detected via electron microscopy in the
      mammalian atria by Kisch. This remarkable discovery signaled the beginning of a
      new field of research that decades later has lead to the concept of the heart as
      an endocrine organ and the establishment of the natriuretic peptide (NP) system.
      In 1981, deBold and colleagues identified from the atrial myocardium the first
      member of the NP family, atrial NP. Thereafter, new members of this growing
      family of cardiac hormones were identified and investigated. The successful story
      of B-type or brain NP (BNP), from its discovery to its use in the diagnosis and
      prognosis of cardiovascular diseases and later as a tool in the treatment of
      acute congestive heart failure, have since taken place. However, the use of
      peptides as chronic therapies has been limited by enzymatic degradation. Chronic
      administration of BNP, particularly in disease states like hypertension and early
      heart failure, could be effective as an antihypertensive therapy and in delaying
      progression of cardiac disease. To date, the use of BNP is limited to patients
      with acute decompensated heart failure, but new strategies are under
      investigation to extend the use of chronic BNP in less severe stages of
      cardiovascular diseases. Innovative technologies have been recently developed
      that allow protection of proteins from enzymatic degradation, making feasible
      oral administration of small proteins such as BNP. This review will focus on the
      potential role of BNP as a new chronic therapeutic strategy in the treatment of
      cardiovascular diseases and will summarize our recent report of the development
      and in vivo evaluation of orally active human BNP.

PMID- 17210473
TI  - Assessment of myocardial microvascular function: new opportunities in fast
      computed tomography.
AB  - It has been increasingly recognized that the initial site of cardiac damage in
      several forms of cardiovascular disease resides in the microcirculation.
      Noninvasive or minimally invasive evaluation of myocardial microvascular
      functional attributes, such as myocardial perfusion or microvascular
      permeability, could be an invaluable tool in the clinical practice. Advances in
      the field of computed tomography over the past three decades culminated in the
      advent of fast scanners, which show promise to provide both fine cardiac anatomic
      detail and quantification of the function of the myocardial microcirculation.
      This review describes the approach and utility of measurements of myocardial
      microvascular function obtained with state-of-the-art cardiac computed
      tomography.

PMID- 17210474
TI  - The regulation of the inflammatory response through nuclear factor-kappab pathway
      by angiotensin IV extends the role of the renin angiotensin system in
      cardiovascular diseases.
AB  - The renin angiotensin system (RAS) participates in the pathogenesis of
      cardiovascular diseases. Although angiotensin II has been considered the effector
      peptide of RAS, accumulating evidence shows that other RAS peptides also posses
      important functions, some of them involved in cardiovascular pathology. Many
      studies support the importance of N-terminal angiotensin degradation product,
      angiotensin IV (AngIV), in the fields of cognition, renal metabolism, and
      pathophysiologic conditions. The novel data discussed here show that AngIV could
      contribute to cardiovascular damage. Angiotensin IV can be generated by
      degradation of angiotensin II, by aminopeptidase (AP) N, or by other proteases,
      which could be activated during tissue damage, suggesting that elevated AngIV
      levels can be found in pathologic conditions. Angiotensin IV binds to a specific
      receptor, AT(4), which has recently been identified as an insulin-regulated AP.
      In vascular cells, correspondence between AT(4) binding sites and insulin
      regulated AP has been described. Angiotensin IV regulates cell growth in cardiac
      fibroblasts, endothelial cells, and vascular smooth muscle cells (VSMCs). In
      VSMC, AngIV, through AT(4), independently of AT(1) and AT(2) receptors, activates
      the nuclear factor-kappaB pathway and up-regulates several nuclear factor-kappaB
      related genes, including the monocyte chemokine monocyte chemoattractant protein
      1, the adhesion molecule intercellular adhesion molecule-1, and the cytokines
      interleukin 6 and tumor necrosis factor alpha. These data indicate that AngIV
      could be involved in the vascular inflammatory response. Thus, in endothelial
      cells and VSMC, AngIV up-regulates plasminogen activator inhibitor-1 expression
      and could participate in thrombus formation. These results reveal novel concepts
      of RAS in the cardiovascular system, suggesting that AngIV could play an active
      role in vascular diseases.

PMID- 17210475
TI  - Smoothelin in vascular smooth muscle cells.
AB  - Smoothelin-A and -B have only been found in fully differentiated contractile
      smooth muscle cells. They are increasingly used to monitor the smooth muscle cell
      differentiation process to a contractile or synthetic phenotype. Vascular
      specific smoothelin-B is the first smooth muscle cell marker that disappears when
      vascular tissues are compromised, for example, in atherosclerosis or restenosis.
      Recently obtained data show that smoothelin deficiency results in a considerable
      loss of contractile potential and hence in impaired smooth muscle function and
      suggest that smoothelins are part of the contractile apparatus.

PMID- 17210476
TI  - AT(1) receptors and control of blood pressure: the kidney and more...
AB  - The renin-angiotensin system (RAS) is a critical regulator of blood pressure and
      fluid homeostasis. The components of the RAS including renin, angiotensin
      converting enzyme, and angiotensin receptors are expressed throughout the body in
      tissues that may impact blood pressure control. Blocking actions of individual
      components of the RAS including renin, angiotensin-converting enzyme, or the type
      1 (AT(1)) receptor lowers blood pressure. Although it has been suggested that
      control of sodium excretion by the kidney is the dominant mechanism for blood
      pressure regulation by the RAS, pharmacologic antagonists or conventional gene
      targeting experiments globally interrupt the RAS and cannot discriminate its
      actions in the kidney from other tissue compartments. Recent experiments with the
      use of kidney cross-transplantation and genetically engineered mice suggest
      independent and equivalent effects of angiotensin II acting via AT(1) receptors
      in the kidney and in extrarenal tissues to maintain the normal level of blood
      pressure. However, the nature and relative contributions of these actions may
      differ in hypertension.

PMID- 17210478
TI  - Management of common head and neck masses.
AB  - Head and neck masses are a common clinical concern in infants, children, and
      adolescents. The differential diagnosis for a head or neck mass includes
      congenital, inflammatory, and neoplastic lesions. An orderly and thorough
      examination of the head and neck with an appropriate directed workup will
      facilitate the diagnosis. The most common entities occur repeatedly within the
      various age groups and can be differentiated with a clear understanding of
      embryology and anatomy of the region, and an understanding of the natural history
      of a specific lesion. Congenital lesions most commonly found in the pediatric
      population include the thyroglossal duct cyst and the branchial cleft and arch
      anomalies. The inflammatory masses are secondary to local or systemic infections.
      The most common etiology for cervical adenopathy in children is reactive
      lymphadenopathy following a viral or bacterial illness. Persistent adenopathy
      raises more concerns, especially enlarged lymph nodes within the posterior
      triangle or supraclavicular space, nodes that are painless, firm, and not mobile,
      or a single dominant node that persists for more than 6 weeks should all heighten
      concern for malignancy. In this review, we discuss the current principles of
      surgical management of the most common head and neck masses that present to
      pediatricians and pediatric surgeons.

PMID- 17210479
TI  - Minimal access thoracic surgery in the pediatric population.
AB  - Thoracoscopy was initially described for use in children to obtain pulmonary
      biopsy samples in the immunocompromised patient. With refinements in technique,
      development of better instrumentation, and advances in pediatric anesthesia,
      there are now many diagnostic and therapeutic indications for the use of
      thoracoscopy in children. One of the most common indications includes pleural
      debridement for empyema. Many centers consider this the optimal approach for
      biopsy of mediastinal lesions and excision of bronchogenic or duplication cysts.
      The technique is useful for pleural disorders, such as spontaneous pneumothorax
      and chylothorax. Thoracoscopy has been used to achieve exposure for spinal
      diskectomy in children with thoracic scoliosis, and newer techniques are being
      developed in performing anatomic lobectomies, repair of esophageal atesias, and
      closure of diaphragmatic hernias. The role of the robot in pediatric thoracoscopy
      is still in the early stages of definition.

PMID- 17210480
TI  - Current management of hypertrophic pyloric stenosis.
AB  - Hypertrophic pyloric stenosis (HPS) is a common condition affecting infants that
      presents with progressive projectile nonbilious vomiting. The pyloric portion of
      the stomach becomes abnormally thickened and manifests as gastric outlet
      obstruction. The cause is unknown. Pyloromyotomy remains the standard of
      treatment and outcome is excellent. This article reviews the diagnostic work up
      and imaging, preoperative resuscitation, the various surgical approaches used,
      and the effect of subspecialty training on outcomes after pyloromyotomy.
      Postoperative care and the variety of postoperative feeding regimens applied
      after pyloromyotomy are reviewed, as well as intra- and postoperative
      complications. Finally, medical management, in lieu of surgery, is discussed.

PMID- 17210481
TI  - Current management of appendicitis.
AB  - Appendicitis is the most common surgical disease of the abdomen in children.
      Pediatric appendicitis varies considerably in its clinical presentation,
      contributing to delay in diagnosis and increased morbidity. The methods of
      diagnosis and treatment of appendicitis also vary significantly among clinicians
      and medical centers according to the patient's clinical status, the medical
      center's capabilities, and the physician's experience and technical expertise.
      Recent trends include the increased use of radiologic imaging, minimally invasive
      and nonoperative treatments, shorter hospital stays, and home antibiotic therapy.
      Little consensus exists regarding many aspects of the care of the child with
      complicated appendicitis. This article examines the most debated aspects of the
      diagnosis and management of the diseased pediatric appendix.

PMID- 17210482
TI  - Current management of umbilical abnormalities and related anomalies.
AB  - Prenatally, the umbilicus is of paramount importance, providing the gateway
      between the mother and the fetus. As the fetus becomes increasingly autonomous at
      the end of the second month of fetal life, the connections (vitelline, urachal)
      diminish in significance and involute. Disturbances in this process can result in
      a wide variety of abnormalities, ranging from relatively minor defects identified
      at birth (umbilical granulation tissue) to life-threatening complications
      quiescent until late adulthood (urachal carcinoma). This section will review the
      'state of the art' in evaluation and management of these umbilical and related
      abnormalities.

PMID- 17210483
TI  - Current management of hernias and hydroceles.
AB  - The repair of inguinal hernia and hydrocele is one of the most common operations
      in a pediatric surgery practice. This work reviews current concepts in the
      management of the inguinal hernia and hydrocele. The authors describe current
      concepts of anesthetic management of children undergoing repair of inguinal
      hernia. The authors also discuss current management of the contralateral hernia,
      hernias in premature infants, and the management of an incarcerated hernia. In
      addition, the authors discuss the role of laparoscopy in the surgical treatment
      of an inguinal hernia and its application for investigation of the contralateral
      inguinal canal.

PMID- 17210484
TI  - Current management of the acute scrotum.
AB  - Pediatric surgeons and urologists are often asked to evaluate boys with acute
      scrotal pain and inflammation. Although there are myriad etiologies for this
      syndrome, testicular torsion should be at the top of the list. It is the one
      diagnosis that must be made accurately and rapidly if there is any hope for
      testicular salvage. The purpose of this article is to update/review the
      appropriate evaluation and management of the acute scrotum and to guide the
      clinician in distinguishing testicular torsion from the other conditions that
      commonly mimic this surgical emergency.

PMID- 17210485
TI  - Current management of the undescended testicle.
AB  - Cryptorchidism, where either one or both testes fails to migrate to the base of
      the scrotum, affects 4% to 5% of full-term and 9% to 30% of premature males at
      birth. The testis can be found in any position along its usual line of descent;
      however, approximately 80% will be located in the inguinal region, just outside
      the inguinal canal. Early correction, from 3 to 6 months of age, is currently
      advised. The preferred means of investigation and subsequent surgical
      intervention are dependent on the position of the cryptorchid testis. Risks
      associated with cryptorchidism include infertility and malignancy. The aim of
      appropriate management is to minimize these, and any other, associated
      complications.

PMID- 17210486
TI  - Common anorectal problems.
AB  - Children, just as adults, have a variety of common anorectal problems that can be
      quite bothersome. The presentation of these problems may be age-specific.
      Abscesses, fistulas, and fissures appear more commonly in infants and young
      children, whereas hemorrhoids and pilonidal disease are more common in teens and
      young adults. Fissures often can be treated medically but may require surgical
      treatment with lateral internal sphincterotomy. Abscesses and fistulas are common
      in infant males, especially robust infants who are breastfed. They may resolve
      with medical therapy but anal fistulotomy is not infrequently required.
      Hemorrhoids are rare in young children but may be an issue for teenagers. Acute
      symptomatic lesions may require excision if local measures cannot control the
      symptoms. Finally, pilonidal disease is a difficult problem for the patient and
      the surgeon. Persistently symptomatic lesions demand some type of surgical
      treatment but wound healing is poor in the intergluteal cleft region. More
      extensive procedures requiring the transfer of fasciocutaneous flaps may be
      necessary to provide definitive relief. Anorectal problems in infants and
      children are frequent and bothersome. Although most are not associated with
      tremendous morbidity, they can lead to much patient and parent anxiety as well as
      frequent medical consultation until the problem is successfully treated or
      resolves.

PMID- 17210487
TI  - Standard practice and evolving trends in pediatric intravenous access.

PMID- 17210488
TI  - An acidosis and electrolyte dilemma: conclusion.

PMID- 17210489
TI  - Research study designs: non-experimental.

PMID- 17210491
TI  - Pilot safety survey 2005: what pilots are saying.

PMID- 17210492
TI  - Results and recommendations from the helicopter EMS pilot safety survey 2005.
AB  - INTRODUCTION: In 2005, the Pilot Safety Study Group (PSSG), consisting of members
      of the Association of Air Medical Services Research Committee, wrote,
      distributed, and analyzed a survey of helicopter pilots regarding their
      knowledge, attitude, and perspectives on safety in the field of air medical
      transport. METHODS: The Pilot Safety Survey 2005 (PSS2005) was based on another
      survey--one that was sponsored by Helicopter Association International (HAI) and
      National EMS Pilots Association (NEMSPA) and administered to pilots in 2001. The
      PSS2005 pared questions down so that the survey could be completed in 15 minutes
      on the internet, and the answers were organized in a manner to simplify analysis.
      An electronic link to the survey was distributed in a non-randomized fashion to
      HEMS pilots using the mailing lists of various operators and HEMS programs.
      Questions were clustered into eight groupings of safety, with a majority of
      responses being categorical, lending themselves to cross-tabulations. RESULTS:
      The information gathered indicated that Helicopter EMS (HEMS) pilots are very
      experienced, with the average pilot logging 6,625 flight hours. Collectively,
      they took responsibility for HEMS accidents; with 92% of total respondents citing
      "pushing weather minimums" and 82% citing "pilot decision making" as the main
      reasons for crashes. Crew resource management (CRM) was well appreciated by the
      pilots; there appeared to be a positive correlation with programs that offer
      their employees CRM and the pilots' general perspective on safety. The survey was
      also clear that amongst 40% of the respondents, mission-oriented training needs
      improvement, and 74% responded that more realistic training in flight simulators
      would improve safety overall. Finally, 57% of the pilots both desired night
      vision goggles or devices (NVG/NVD) and believed that their usage would improve
      safety in the field of air medical transport (55% vs 45%, P = .0025).
      CONCLUSIONS: Although the recommendations from the PSS2005 are lacking in
      definite evidence for a decrease in HEMS crashes, we consider the direct input
      from pilots as critical in the absolute elimination of crashes in Helicopter EMS
      (Vision Zero). Pilots are, after all, the very ones held responsible for HEMS
      crashes. Based on these findings, the PSSG hopes that the HEMS community will
      incorporate the following recommendations into their standard practices. We
      recommend that all HEMS operators have annual and regular CRM training. We
      recommend that all HEMS pilots have annual and regular training in realistic
      flight simulators. Finally, we recommend that all HEMS aircraft be in possession
      of NVGs, and if this is not possible (eg, light pollution from a highly urbanized
      region or cost-benefit issues), then to have annual and regular mission-oriented
      nighttime training.

PMID- 17210493
TI  - Sleep debt and outside employment patterns in helicopter air medical staff
      working 24-hour shifts.
AB  - INTRODUCTION: Twenty-four hour availability creates physiological and
      psychological challenges for air medical teams. The 24-hour shift (24H) is a
      common staffing pattern in the air medical community. We report sleep dept and
      pre-duty activity patterns for 24H medical staff members at helicopter air
      medical transport programs. METHODS: An anonymous survey collecting self-reported
      sleep quantities for off-duty, immediate pre-duty, and on-duty periods, along
      with self-reported outside employment patterns, was distributed to medical team
      members at cluster sample of 10 rotor wing air medical programs selected by
      stratified random sample to ensure geographic and operational diversity. Both
      matched-sample comparisons of sleep quantities in different phases of the duty
      cycle and independent-sample comparisons between staff with and without outside
      employment had 80% power to detect a difference in means of 60 minutes at a 0.05
      two-sided significance level using the appropriate t-test. Descriptive statistics
      are also reported; means are reported with the standard deviation. RESULTS: A
      total of 138 surveys were returned (69.0%) and the 133 (66.5%) that were fully
      completed were utilized for analysis. 24H crewmembers average nearly the same
      amount of sleep in 24 hour periods on both duty and non-duty days (6.9 +/- 1.3 v.
      6.4 +/- 1.8 hours, p = NS, range 3 - 10 for duty days and 4 - 10 for non-duty
      days). On duty, they average 1.1 +/- 1.3 hours of sleep in the first half of
      their shifts (range 0 to 5) and 5.3 +/- 1.4 hours in the overnight portion (range
      2 - 9). The lowest amount of on-duty sleep reported in the past 30 days ranged
      from 0 to 6 hours, averaging 1.9 +/- 1.7 hours. The minimum pre-duty sleep
      reported by 24H crewmembers prior to any shift in the past month averaged 4.6 +/-
      1.6 hours (range 0-8), with 3.8% having reported in the past month with no sleep
      before their 24-hour shift. Outside employment (OE) in addition to the flight
      position was common for 24H crewmembers (81.1% of respondents). Pre-duty sleep
      did not differ significantly between 24H crewmembers with and without OE, but
      16.3% of surveyed 24H crewmembers with OE had reported for flight duty within
      eight hours of leaving OE within the past 30 days. CONCLUSION: In the programs
      surveyed, 24H crewmembers completed an average duty cycle with little sleep debt
      and were unlikely to be sleepless prior to reporting for a shift. OE is common
      for 24H medical staff and some personnel report for flight duty within eight
      hours of leaving an OE position. As the industry considers the impact of fatigue
      on operational safety, shift length, on-duty rest, and outside employment will be
      important considerations.

PMID- 17210494
TI  - Medically appropriate use of helicopter EMS: the mission acceptance/triage
      process.
AB  - INTRODUCTION: Appropriate use of helicopter emergency medical services (HEMS)
      ensures the maximum impact of a limited resource on improved health outcomes.
      Overtriage increases real and opportunity costs and may unjustifiably expose the
      program to small but inherent safety risks. The purpose of this study is to
      describe the mission acceptance process for an integrated, provincially based
      HEMS program and determine its utilization patterns. METHODS: This is a
      retrospective review of patient care and administrative databases. All missions
      were reviewed to determine whether they were medically appropriate.
      "Appropriateness" was defined a priori as requiring admission to a critical care
      unit, death during transportation or in first 24 hours, or in the case of trauma,
      an injury severity scale (ISS) score > or = 12. Overtriage was defined as not
      meeting these a priori definitions. RESULTS: Five hundred eighty-four missions
      were reviewed from March 31, 2003 through December 31, 2004. Our mission
      acceptance process consists of three distinct but complementary phases: ongoing
      outreach education, scanning by dispatchers in an integrated dispatch center, and
      a clinician to online physician discussion about each case. The overall
      overtriage rate was 13.1%. CONCLUSION: The rate of medically appropriate missions
      in this system is relatively high. Prospective research is required to improve
      HEMS triage systems.

PMID- 17210495
TI  - Sidestream end-tidal carbon dioxide monitoring during helicopter transport.
AB  - INTRODUCTION: End-tidal carbon dioxide (EtCO(2)) monitoring is standard of care
      for intubated patients. Sidestream technology also allows EtCO(2) monitoring in
      non-intubated patients. This is the first study to evaluate the feasibility of
      monitoring sidestream EtCO(2) on intubated and non-intubated patients during
      helicopter transport. SETTING: An air medical transport program serving two level
      1 trauma centers. METHODS: In this prospective observational study, sidestream
      EtCO2 was monitored in 100 consecutive patients transported by helicopter. Flight
      nurses rated the difficulty posed by various factors of sidestream monitoring. An
      experienced flight nurse and a clinical engineer evaluated waveforms and EtCO(2)
      values. RESULTS: Only 1 of the 100 transported patients required a change from
      sidestream to mainstream EtCO(2) monitoring. Moisture was noted in the tubing of
      two patients, and one was changed to mainstream. Eleven patients had occluded
      nares but were not changed to mainstream monitoring. On a 5-point Likert scale,
      responses to statements regarding difficulty with length of tubing, patient
      tolerance, and interference with patient care produced mean scores of 0.5 (range,
      0-3). Responses regarding difficulty securing the cannula yielded a mean score of
      0.7 (range, 0-3). Of 1,685 (99%) recorded EtCO(2) values, 1,668 met pre
      established criteria for "consistent." Alveolar plateaus were identified in 81 of
      94 (86%) patient waveforms by the flight nurse and 73 of 94 (78%) patient
      waveforms by the clinical engineer. CONCLUSION: Sidestream EtCO(2) monitoring is
      feasible during air medical transport of both intubated and non-intubated
      patients. The mechanism was easy to use, and consistent numeric values and
      waveforms with alveolar plateaus were obtained in a large majority of readings.

PMID- 17210496
TI  - Suboptimal pharmacotherapy in a tribal nursing home.
AB  - OBJECTIVE: Suboptimal medication use among nursing home (NH) residents is common.
      NH residents tend to be older, suffer from multiple conditions, and take numerous
      medications, increasing their risk of serious complications. This article
      examines pharmacotherapy in a rural, tribally owned NH. DESIGN: Medical records
      were reviewed and case studies were conducted by a team composed of a medical
      anthropologist, psychiatrist, and geriatrician. SETTING: A rural, American Indian
      owned NH in the US northern plains. PARTICIPANTS: 40 American Indian and 5
      EuroAmerican NH residents. MEASUREMENTS: Minimum Data Set assessments, admission
      records, care plans, social histories, prescription lists, and behavioral
      consultation reports. RESULTS: Potential underuse affected almost 75% of
      residents; undertreatment of depressive and psychotic/agitated symptoms was
      especially common. Potential inappropriate use, especially of analgesics,
      psychotropics, and antihistamines, affected 30% of residents. A smaller, but
      still substantial, number of residents (21%) experienced potential overuse, much
      of which involved anticonvulsants, antibiotics, cardiovascular, and psychotropic
      agents. The prescription of 10 or more medications was significantly associated
      with potential drug interactions, as well as underuse, inappropriate medication
      use, and overuse. CONCLUSIONS: Psychotropic medications were the most potentially
      problematic medication category, and were strongly implicated in potential
      underuse, inappropriate use, and overuse. Fewer medications; the discontinuation
      of drugs known to be potentially problematic for NH residents; modification of
      psychotropic medication regimens; use of cognitive-enhancing medications where
      appropriate; implementation of an electronic medical record system; and greater
      use of nonpharmacological behavioral interventions may have substantially
      improved residents' treatment regimens.

PMID- 17210497
TI  - Considering the employee point of view: perceptions of job satisfaction and
      stress among nursing staff in nursing homes.
AB  - OBJECTIVE: To document job satisfaction and sources of stress among nursing staff
      working in nursing homes and to evaluate the extent to which the reasons of
      stress differ by type of nursing staff. DESIGN: Cross-sectional study. SETTING:
      Twenty-five nursing homes in North Carolina participating in a demonstration
      project of a new model of long-term care pharmacy. PARTICIPANTS: Nurses and
      nursing assistants employed at the time of the survey in the spring and summer of
      2002 (n = 1283). MEASUREMENTS: Health Professional Stress Inventory modified for
      use in the nursing home setting and ratings of job satisfaction. RESULTS: The
      situations most stressful for nurses were not having enough staff, having too
      much work to do, interruptions, having non-health professionals determine how to
      do their job, poor pay, and ultimately being responsible for patient outcomes.
      The top most stressful situations for nursing assistants included poor pay, not
      enough staff, and too much work to do. Nursing assistants were more likely than
      nurses to report stress because they do not have adequate information regarding a
      patient's condition. Nurses were more likely than nursing assistants to report
      stress because non-health professionals (eg, surveyors) determine how they must
      do their job. CONCLUSIONS: The findings of this study support the need to improve
      recognition for nursing, improve staffing, and provide competitive compensation
      in nursing homes.

PMID- 17210498
TI  - Depression as a risk factor for nursing home admission among older individuals.
AB  - OBJECTIVES: Depression is common among those aged 65 and older and has been
      associated with increased morbidity and mortality. This study investigated
      whether individuals enrolled in Medicare+Choice with symptoms of depression as
      measured using the mental health scale from the SF-36 were at increased risk of
      using nursing home services. DESIGN: A Cox proportional hazards model was used.
      SETTING: The study investigated community-based adults aged 65 and older.
      PARTICIPANTS: Participants were individuals aged 65 years and older enrolled in
      Medicare+Choice who responded to the Health Outcomes Survey and were not
      institutionalized or incapable of responding for themselves at the time of survey
      administration. MEASUREMENTS: The purpose of the study was to predict the risk of
      admission to a nursing home over time, controlling for variables related to
      demographics, comorbidity, age, and functional status. RESULTS: The results
      indicated that, even after controlling for physical health, functional status,
      age, demographics, and socioeconomic status, Medicare+Choice enrollees over the
      age of 65 experiencing symptoms of depression as identified by the SF-36 are at
      increased risk of using nursing home services. CONCLUSIONS: These results have
      implications for payers of nursing home services such as Medicare and Medicaid as
      well as for providers and the families of older individuals. While the results do
      not prove that prevention is possible, they do suggest that better identification
      and treatment of depression reduce the risk of nursing home admission. Even if
      nursing home placement cannot be avoided, it is possible that the individual's
      quality of life could be significantly enhanced by better diagnosis and treatment
      of depression. These findings have implications beyond the Medicare+Choice
      population.

PMID- 17210499
TI  - A multi-center blinded prospective study of urine neural thread protein
      measurements in patients with suspected Alzheimer's disease.
AB  - OBJECTIVE: To investigate the utility of a clinical laboratory ELISA format assay
      that measures neural thread protein (NTP) in urine in the assessment of patients
      presenting with cognitive symptoms. DESIGN: A prospective blinded multicentered
      study. SETTING: Eight US specialty clinics for the evaluation of cognitive or
      memory disorder or dementia, including memory disorder and dementia clinics,
      neurology clinics, and psychiatry clinics, in 8 states. PARTICIPANTS:
      Prospectively enrolled consecutive patients who were newly referred to a
      specialty clinic for assessment of cognitive or memory disorder symptoms or
      dementia to rule out or rule in Alzheimer's disease (AD). MEASUREMENTS:
      Participants provided a first morning urine sample for UNTP measurement for
      testing at a central core laboratory and subsequently went through specialized
      diagnostic evaluations in accordance with established clinical criteria. Urine
      NTP measurement was compared to the diagnostic categorization of the patients as
      probable or possible AD (according to National Institute of Neurological
      Communicative Disorders and Stroke and the Alzheimer Disease and Related
      Disorders Association [NINCDS-ADRDA] criteria), mild cognitive impairment (MCI)
      (according to Quality Standards Subcommittee of the American Academy of Neurology
      [AAN] criteria) or definite non-AD. Clinical diagnoses were made without
      reference to UNTP measurement; the testing laboratory was blinded to both patient
      identity and clinical diagnoses. RESULTS: A total of 168 enrolled and consented
      patients provided qualifying urine samples and completed specialized diagnostic
      workups. There were 91.4% of subjects with probable AD, 37.7% of subjects
      categorized as possible AD, and 48.6% of subjects with MCI who had an elevated
      NTP measurement (>22 microg/mL). There were 90.7% of subjects diagnosed as
      definite non-AD who had a normal NTP measurement (< or =22 microg/mL).
      CONCLUSION: Noninvasive UNTP test results are potentially helpful as part of the
      workup of dementia for the nonspecialist to help in the decision as to whether
      referral and/or more detailed investigation is advisable.

PMID- 17210500
TI  - Electronic health record implementation in community nursing homes.
AB  - INTRODUCTION: The Electronic Health Record (EHR) is being advocated as a tool to
      improve patient care. Nationwide initiatives are under way to determine how to
      implement EHR. To date, community nursing homes have not been involved in that
      effort. Many reasons, including multiple providers in a home, physical structure
      of a facility, multiple facilities, high costs of implementation, and maintenance
      of an EHR, hinder efforts to establish such a record in a nursing home. Convinced
      that an EHR would improve resident care, we undertook a project to establish an
      EHR in 11 community nursing homes. METHODS: Boston University Geriatric Services
      and Boston Medical Center partnered with 11 community nursing homes in the
      Boston, MA, area to introduce GE Centricity as the medical provider's medical
      record for the residents under the care of this medical practice. This effort
      included allowing the software to be used at various sites, providing hardware,
      and establishing Internet connectivity. RESULTS: All 11 of the nursing homes
      served by Boston University Geriatric Services have been connected to the system.
      DISCUSSION: It is possible to establish an EHR in a diverse, unrelated group of
      nursing homes. This has allowed for improved communication between providers,
      consultants, hospital, and nursing home staff.

PMID- 17210501
TI  - The application of evidence-based principles of care in older persons (issue 6):
      urinary incontinence.

PMID- 17210502
TI  - A person-centered workplace: the foundation for person-centered caregiving in
      long-term care.
AB  - OBJECTIVE: This study seeks to understand what role managers and the work setting
      they create play in a nursing facility that seeks to make a transition to person
      centered care. DESIGN: The study uses a human-relations framework to test 3
      propositions: Managers play a critical role in the satisfaction, loyalty and
      commitment (ie, the engagement) of their staff; managers construct a person
      centered workplace that deepens staff engagement; and engaged staff promote the
      well-being of the residents. SETTING AND PARTICIPANTS: The study draws on
      responses of Certified Nurse Assistants (CNAs) and families of residents
      collected in 2 satisfaction surveys conducted in 156 nursing facilities. It also
      uses state inspection survey data from the same facilities. MEASUREMENTS: The
      analysis uses measures of satisfaction, loyalty, and commitment as well as 6
      scales of quality; 3 as they pertain to staff and 3 as they pertain to families.
      Data reduction, correlational, and risk analyses assess how managers and the work
      environment affect CNA engagement and the quality of caregiving. RESULTS:
      Management approach and the work environment are powerful predictors of CNA
      satisfaction, loyalty, and commitment. The work environment also correlates with
      how families and state surveyors evaluate quality in a nursing facility.
      CONCLUSION: The managers and the work setting they create hold primacy in the
      work life of the CNAs. Caring managers fashion a person-centered workplace
      conducive to turn workers into devoted caregivers. When the workplace adds
      quality to the life of caregivers, the caregivers add quality to the life of the
      resident.

PMID- 17210503
TI  - The consultant pharmacist and the physician in the nursing home: roles,
      relationships, and a recipe for success.
AB  - Nursing homes must provide sophisticated medical and personal care to a broad
      spectrum of residents and patients. Medications are an increasingly important
      part of that care. The risks and benefits of medications are widely published,
      but not necessarily recognized in the care of individual patients. Decisions
      about medications must be made in the proper context of the patient. Medications
      are often indicated for various illnesses, symptoms, and risk factors, but
      clinically significant adverse consequences of medications are common and
      typically mimic common syndromes. Timely recognition and management of adverse
      consequences requires vigilance and a high index of suspicion. Many factors
      influence medication prescribing and use in the nursing home. Newly updated OBRA
      surveyor guidance emphasizes the importance of following the full care process in
      implementing, dosing, monitoring, and adjusting medications. Physicians and
      consultant pharmacists have prominent, complementary roles in addressing
      medications in the nursing home. The purpose of this article is to clarify these
      roles, identify their basis (primarily, the care process), and discuss how
      physicians and consultant pharmacists can collaborate effectively to optimize
      medication use and minimize preventable adverse consequences.

PMID- 17210504
TI  - The medical director, JAMDA, and the twenty-first century.

PMID- 17210505
TI  - The 'plaice' of language.

PMID- 17210506
TI  - An experimental study comparing the effects of combined transcutaneous acupoint
      electrical stimulation and electromagnetic millimeter waves for spinal pain in
      Hong Kong.
AB  - OBJECTIVES: To compare the efficacy of combined transcutaneous acupoint
      electrical stimulation (TAES) and electromagnetic millimeter wave (EMMW) therapy
      as an add-on treatment for pain relief and physical functional activity
      enhancement among adults with sub-acute non-specific spinal pain in either the
      low back or neck. DESIGN: A non-blinded study with data obtained before,
      immediate, one week and three months after intervention. SETTING: The Telehealth
      Clinic and Community Centre, Hong Kong. PARTICIPANTS: Forty-seven subjects with
      either sub-acute neck or low back pain. INTERVENTION: Subjects were randomly
      allocated to either an intervention group (n=23) or a control group (n=24). These
      groups were then divided into subgroups according to the site of their spinal
      pain-neck or back. The intervention group had eight treatments over a three-week
      period of TAES and EMMW. OUTCOME MEASURES: Changes from baseline to the end of
      treatment were assessed at intervals of one week and three months on either neck
      or low back pain intensity [by Visual Analogue Scale (VAS)]; stiffness level;
      stress level; neck or low back lateral flexion and forward flexion in cm, and
      interference with daily activities. RESULTS: The baseline VAS scores for the
      intervention and control groups were 5.34 and 5.18 out of 10, respectively (P
      value=0.77). At the one week and three month assessments, there were no
      significant differences between the groups-VAS (P value=0.09 and 0.27,
      respectively). A further subgroup of chronic pain sufferers (n=31) was identified
      and these had significantly reduced pain intensity at the one week assessment (P
      value=0.04) but this was not sustained at post three months after treatment (P
      value=0.15). Improvements in stiffness level, stress level, and functional
      disability level in the intervention group were not significant. CONCLUSIONS: Our
      study shows that there was a reduction in pain intensity, stress and stiffness
      level immediately after the eight sessions of treatment (TAES and EMMW), though
      the effect is not sustained after a week. No pain relief was found with the neck
      pain subgroup. However, the reduction in subjective average pain intensity among
      the chronic pain subgroup was sustained at the post one week assessment for the
      intervention group but not at the post three month assessment.

PMID- 17210507
TI  - Sunflower therapy for children with specific learning difficulties (dyslexia): a
      randomised, controlled trial.
AB  - The aim of the study was to determine the clinical and perceived effectiveness of
      the Sunflower therapy in the treatment of childhood dyslexia. The Sunflower
      therapy includes applied kinesiology, physical manipulation, massage, homeopathy,
      herbal remedies and neuro-linguistic programming. A multi-centred, randomised
      controlled trial was undertaken with 70 dyslexic children aged 6-13 years. The
      research study aimed to test the research hypothesis that dyslexic children 'feel
      better' and 'perform better' as a result of treatment by the Sunflower therapy.
      Children in the treatment group and the control group were assessed using a
      battery of standardised cognitive, Literacy and self-esteem tests before and
      after the intervention. Parents of children in the treatment group gave feedback
      on their experience of the Sunflower therapy. Test scores were compared using the
      Mann Whitney, and Wilcoxon statistical tests. While both groups of children
      improved in some of their test scores over time, there were no statistically
      significant improvements in cognitive or Literacy test performance associated
      with the treatment. However, there were statistically significant improvements in
      academic self-esteem, and reading self-esteem, for the treatment group. The
      majority of parents (57.13%) felt that the Sunflower therapy was effective in the
      treatment of learning difficulties. Further research is required to verify these
      findings, and should include a control group receiving a dummy treatment to
      exclude placebo effects.

PMID- 17210508
TI  - Cat's claw: an Amazonian vine decreases inflammation in osteoarthritis.
AB  - Cat's claw (Uncaria tomentosa and Uncaria guianesis) is a medicinal plant from
      the Amazon commonly used to treat disorders such as arthritis, gastritis and
      osteoarthritis. The mechanism of cat's claw appears to be as an inhibitor of
      TNFalpha and antioxidant. Understanding the processes in osteoarthritis may
      facilitate and clarify the potential role of cat's claw as a complementary
      therapy to assist in the reduction of pro-inflammatory mediators and effectors.
      The clinical relevance of this therapy as a viable modality of intervention will
      be discussed.

PMID- 17210509
TI  - Actions speak louder than words: mainstream health providers' definitions and
      behaviour regarding complementary and alternative medicine.
AB  - The purpose of this paper is to explore how mainstream practitioners define and
      categorize complementary and alternative medicine (CAM) as one component of
      assessing their views. The following themes emerged from interviews with Canadian
      physicians, midwives and nurses: epistemological, evidence-based, medical domain,
      political-regulatory, funding-based, and role-based definitions of CAM. We also
      assess any possible links to their behaviour vis-a-vis CAM. We found that
      classifying something as CAM does not appear to inhibit most providers from
      recommending, referring for, or supporting their patients' use of these
      treatments. In conclusion, we highlight that despite their clear definitional
      boundaries around CAM, providers tend to evaluate each individual therapy on its
      own merits, taking other situational factors into consideration.

PMID- 17210510
TI  - Herbal care for reproductive health: ethno medicobotany from Uttara Kannada
      district in Karnataka, India.
AB  - Traditional herbal medicine is predominantly practiced by the rural people of
      India, especially remote areas such as the Uttara Kannada District in Western
      Ghats of Karnataka. Local traditional healers play an important role in the
      management of reproductive health problems of the native population due to socio
      economical and geographical factors. In the present study, 92 traditional
      medicine practitioners/healers from various regions of Uttara Kannada district
      were interviewed to collect information on the use of herbal treatments for a
      range of female and male reproductive disorders. Information was also collected
      on the method of preparation, dose and duration along with the botanical names,
      family and local names of the medicinal plants. The plants were then collected
      and identified. A total of 18 formulations from 25 plant species belonging to 17
      families were identified, which are commonly used to treat 12 different
      reproductive ailments. This study identifies herbal remedies not previously
      documented, that are used by indigenous people in the treatment of reproductive
      disorders. Additionally, the paper highlights the need to retain and explore the
      rich biodiversity associated with Indian rain forests that may result in the
      discovery of new medical treatments. Finally, this paper notes the continuing
      reliance on herbal medicines and healing traditions by local people in remote
      areas. Understanding and working with local healers and tribes provides a unique
      opportunity to learn about the use of potentially new herbal and plant
      medications.

PMID- 17210511
TI  - Communication between CAM and mainstream medicine: Delphi panel perspectives.
AB  - Healthcare practitioners' models of health affect their patient interactions and
      services. We surveyed mainstream (MM), integrative (IM) and CAM providers to
      investigate their models of health. This study generated ideas for actions to
      improve MM/CAM communication based on survey findings. Through the Delphi
      technique, a panel of 14 MM, IM and CAM experts participated in two rounds of
      questioning regarding survey findings. MM panel members were less supportive of
      almost all suggestions for actions than IM and CAM members. Suggestions most
      likely to be implemented were enabling the patient to take an active role in
      care, establishing understanding between patient and practitioner of treatment
      and its goals, fostering patients' taking responsibility for their health and
      communicating about patient assessment in ways understandable to others. Actions
      to foster better MM/CAM communication promote focus by a team of providers on the
      patient's goals, functioning and involvement in their care.

PMID- 17210512
TI  - An analysis of paper-based sources of information on complementary therapies.
AB  - This study involved an investigation into the availability of paper-based
      publications containing information on complementary therapies (CTs) within a
      single cancer centre in the North West. The publications were collected during a
      1-week period in July 2003 from the four most likely locations in the site that a
      patient would visit, to ensure that the research related to data that was readily
      available. An evaluation grid was developed, and the quantity and quality of the
      data presented about CTs were analysed. A total of 80 publications were
      collected. Forty-five (56.3%) related to breast cancer specifically, of which
      only six (20.7%) made reference to CTs. Thirty-five (43.8%) related to cancer in
      general, of which only 16 (45.7%) made reference to CTs. The type of information
      relating to CTs was of very limited value to assist in reaching any decisions as
      to their use. As a result, it was recommended that the healthcare service prepare
      and publish a leaflet, specifically relating to the use of CTs in the treatment
      of cancer, to be freely available within the site for the use of its breast
      cancer patients.

PMID- 17210513
TI  - Auriculotherapy on low back pain in the elderly.
AB  - The objective of the study was to examine the effectiveness of auriculotherapy
      using magnetic pellets for the elderly suffering from low back pain (LBP). Sixty
      participants who were 60-years old or above and had been suffering from LBP were
      recruited. Participants were randomly allocated to receive auriculotherapy on a 3
      week basis using either Semen Vaccariae (control group=30) or magnetic pellets
      (experimental group=30). Seven auricular acupoints that are believed to have an
      effect on LBP were selected. Treatment effects were evaluated using the Chinese
      Pain Intensity Verbal Rating scale (VRS). The experimental group had indeed
      experienced a significant improvement in pain relief when compared with the
      control group; and the therapeutic effects were sustained at 2 and 4-week follow
      up periods after the therapy. Findings of this study demonstrated that
      auriculotherapy using magnetic pellets significantly reduce the pain intensity
      level of the elderly suffering from non-specific LBP.

PMID- 17210514
TI  - Therapy-related myelodysplastic syndrome: morphologic subclassification may not
      be clinically relevant.
AB  - In practice, cases of therapy-related myelodysplastic syndrome (t-MDS) are often
      classified according to morphologic schemes used for de novo MDS. However, there
      are few data addressing the appropriateness of such classification. We studied
      155 patients with therapy-related acute myeloid leukemia (t-AML)/t-MDS to
      determine whether subclassification by the World Health Organization (WHO)
      criteria for de novo MDS provides prognostic information in t-MDS. In addition,
      we assessed whether cytogenetic stratification by the International Prognostic
      Scoring System (IPSS) guidelines or karyotypic complexity was prognostically
      important. We found no differences in median survival times among patients
      classified into the different WHO subgroup of MDS or according to their bone
      marrow blast percentage; our results indicate a uniformly poor outcome in t-MDS
      regardless of morphologic classification. However, significant survival
      differences correlated with cytogenetic stratification according to IPSS
      guidelines and/or karyotypic complexity. We found only a borderline difference in
      median survival of patients with an initial t-MDS diagnosis compared with
      patients with an initial t-AML diagnosis.

PMID- 17210515
TI  - An approach to interpreting immunohistochemical stains of adenocarcinoma in small
      needle core biopsy specimens: the impact of limited specimen size.
AB  - Interpreting immunohistochemical stains of metastatic adenocarcinoma in small
      needle core biopsy specimens is not always straightforward. We studied the
      effects of small specimen size on immunohistochemical stain results in 20
      colorectal adenocarcinoma hepatic resection specimens stained with cytokeratin
      (CK)7 and CK20. We superimposed 18- and 20-gauge needle core biopsy computer
      images. The results in needle core biopsy specimens correlated best with
      resection specimen results when immunoreactivity was assessed using the 3 images
      with the highest percentage of immunoreactive cells. CK7- and CK20+ needle core
      biopsy specimens correlated best when a higher percentage cut point was used.
      Immunohistochemical stains in small needle core biopsy specimens should be based
      on the regional area with the greatest immunoreactivity. The positive result cut
      point should increase as the amount of stainable carcinoma available for
      interpretation decreases.

PMID- 17210516
TI  - Telomere length and telomerase expression in atypical adenomatous hyperplasia and
      small bronchioloalveolar carcinoma of the lung.
AB  - Telomeres are located at the ends of every human chromosome and are subject to
      shortening at each cycle of cell division in cell senescence and early
      carcinogenesis. We examined the expression of telomeric DNA in 21 atypical
      adenomatous hyperplasias (AAHs) and 40 bronchioloalveolar carcinomas (BACs)
      measuring 2 cm or less in greatest diameter using fluorescent in situ
      hybridization and the expression of human telomerase reverse transcriptase
      (hTERT) messenger RNA (mRNA) in 35 AAHs and 37 BACs. The mean numbers of
      telomeric signals per nucleus were 5.0 in AAH and 7.4 in BAC, each significantly
      less than for normal cells (14.7; P < .0001), but the mean number of telomeric
      signals for AAH and BAC was not statistically different (P = .22). In "benign"
      lung samples, the pattern of expression of hTERT mRNA was barely detected in the
      nonciliated cells of the bronchioles and alveolar type II cells. Positive
      expression of hTERT mRNA was recognized in 66% of AAHs and 97% of BACs. Our
      results demonstrate telomere shortening, indicating its presence in the earliest
      phase of pulmonary carcinogenesis. Telomere length and telomerase may be involved
      in carcinogenesis in the lung.

PMID- 17210517
TI  - Human herpesvirus 8 and iron staining are useful in differentiating Kaposi
      sarcoma from interstitial granuloma annulare.
AB  - We studied 20 granuloma annulare (GA) cases (10 interstitial and 10 palisaded)
      and 19 Kaposi sarcoma (KS) cases (9 "early" and 10 typical). Tissue sections were
      stained for iron, Hale colloidal iron, human herpesvirus 8 (HHV-8), CD31, CD34,
      CD68, collagen IV, factor XIIIa, and MIB-1. Iron staining of dermal tissue
      associated with the lesion was confirmed in all KS cases and no GA cases.
      Immunohistochemical stains for HHV-8 were positive in all 9 cases of early KS and
      most cases (9/10) of typical KS. All 20 cases of GA were HHV-8-. CD31, CD34,
      CD68, factor XIIIa, and MIB-1 were also stained but were difficult to interpret
      and did not seem specific for GA or KS. Iron staining and immunohistochemical HHV
      8 staining in combination were reliable markers for KS compared with interstitial
      GA. MIB-1 fractions of less than 5% favored a diagnosis of GA, whereas fractions
      greater than 10% favored a diagnosis of KS. This study provides novel data
      characterizing iron staining in KS and details the use of iron staining, HHV-8,
      and MIB-1 to distinguish KS from GA.

PMID- 17210518
TI  - Extramural cancer deposits without nodal structure in colorectal cancer: optimal
      categorization for prognostic staging.
AB  - To establish an optimal categorization of cancer deposits without lymph node
      structure (extranodal cancer deposits [EX]) in a prognostic staging system, we
      analyzed 1,027 cases in which patients underwent potentially curative surgery for
      advanced colorectal adenocarcinoma. EX was classified as vascular invasion-type
      (VAS) or non-VAS.A total of 512 foci of EX were identified in 205 patients
      (20.0%), with VAS and non-VAS found in 68 and 182 patients, respectively. The
      hazard ratio for patients with nodal involvement was 3.6 and for patients with
      VAS and non-VAS, 2.5 and 4.7, respectively. Based on multivariate analysis of
      these 3 parameters, only nodal involvement and non-VAS were significant
      prognosticators. By using the Akaike information criterion, N staging was capable
      of predicting survival outcome with the highest accuracy when both nodal
      involvement and non-VAS were treated together as an N factor and VAS was treated
      as a T factor ("new categorization"). The clinical significance of the TNM
      grading system for colorectal cancer would be enhanced if we treat EX as a new
      categorization.

PMID- 17210519
TI  - Clinicopathologic significance of intrathyroidal epithelial thymoma/carcinoma
      showing thymus-like differentiation: a collaborative study with Member Institutes
      of The Japanese Society of Thyroid Surgery.
AB  - Intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like
      differentiation (CASTLE) is a rare malignant tumor having histopathologic
      features similar to those of squamous cell carcinoma of the thyroid and other
      organs and a more favorable prognosis. It is thought to originate from ectopic
      thymic tissue or embryonic thymic rest in or adjacent to the thyroid. We
      investigated clinicopathologic features of 25 cases of ITET/CASTLE. The
      sensitivity and specificity of the pathologic diagnosis of ITET/CASTLE by
      immunohistochemical staining with CD5, a marker of carcinoma of thymic origin,
      were 82% and 100%, respectively. The 5- and 10-year cause-specific survival rates
      were 90% and 82%, respectively. Nodal metastasis and tumor extension predict a
      worse prognosis. Of 22 patients who had curative surgery, 10 (45%) underwent
      adjuvant radiation therapy, and no locoregional recurrence was seen in any of
      them. This is the first study demonstrating the survival curve for patients with
      ITET/CASTLE. Our findings suggest that curative resection followed by radiation
      therapy may effectively prevent locoregional recurrence and CD5 immunostaining is
      useful for diagnosing ITET/CASTLE.

PMID- 17210520
TI  - Reflex UroVysion testing of bladder cancer surveillance patients with equivocal
      or negative urine cytology: a prospective study with focus on the natural history
      of anticipatory positive findings.
AB  - A proportion of patients under surveillance for recurrent bladder carcinoma with
      no immediate evidence of bladder tumor recurrence have positive multitarget
      fluorescence in situ hybridization (FISH; UroVysion, Vysis, Downers Grove, IL)
      results. The course of these "anticipatory positive" cases and the time to
      bladder tumor recurrence remains unknown. We followed up 250 patients with urine
      cytologic results, concurrent multitarget FISH, and cystoscopic examination for
      recurrent urothelial carcinoma. Of 81 cases (32.4%) with FISH-positive results,
      tumor recurrence developed in 60 (74.0%). Of 169 (67.6%) FISH-negative cases,
      recurrent urothelial carcinoma developed in 22 (13.0%). Of 211 patients (84.4%)
      with negative cystoscopic examination results, 56 (26.5%) had positive FISH
      results, and in 35 (62.5%) of these patients, recurrent urothelial carcinoma
      developed. Approximately 27% of patients under bladder carcinoma surveillance
      without immediate evidence of tumor recurrence will have a positive FISH result,
      defining the anticipatory positive subset. In about 65% of this anticipatory
      positive group, recurrent bladder urothelial carcinoma developed within 29
      months.

PMID- 17210521
TI  - Is triple immunostaining with 34betaE12, p63, and racemase in prostate cancer
      advantageous? A tissue microarray study.
AB  - This study aimed to determine the usefulness of a combination of 3
      immunohistochemical markers, 34/betaE12, p63 and alpha-methylacyl coenzyme A
      racemase (AMACR), for the diagnosis of prostate cancer using tissue microarrays
      (TMAs) constructed from 91 archival radical prostatectomy specimens derived from
      the Pathology Department files of Singapore General Hospital, Singapore. Triple
      immunostaining using a cocktail of these 3 antibodies was performed on TMA
      sections using the streptavidin-biotin method. When compared with
      immunohistochemical staining using the individual antibodies, we found that the
      triple cocktail allowed improved evaluation of basal cells in benign glands, and
      AMACR allowed simultaneous corroboration of malignant prostatic glands in the
      same section. We achieved a specificity of 100% with the triple cocktail, and
      sensitivity was acceptable, at 93.8%. In comparison, specificity and sensitivity
      of the individual antibodies were 95.5% and 97.3%, 93.3% and 93.8%, 97.0% and
      95.6% for p63, 34betaE12, and AMACR, respectively. The triple cocktail offers a
      cost-effective way of evaluating abnormal prostatic glandular foci, in addition
      to maximizing the use of small tissue samples from prostatic needle biopsies.

PMID- 17210522
TI  - Immunophenotypic differentiation between neoplastic plasma cells in mature B-cell
      lymphoma vs plasma cell myeloma.
AB  - Some non-Hodgkin lymphomas show marked plasmacytic differentiation. In such
      cases, it may be difficult to differentiate these lymphoma from plasmacytoma or
      myeloma, especially with limited diagnostic material. However, there may be
      immunophenotypic differences in the plasma cells in these disorders that
      distinguish them. This study characterizes the immunophenotypes of neoplastic
      plasma cells in 41 cases of B-lineage non-Hodgkin lymphoma and compares them with
      those in plasma cell myeloma. We found that plasma cells in lymphoma were
      significantly more likely to express CD19, CD45, and surface immunoglobulin and
      less likely to express CD56 than those in myeloma. We further show that CD 19 and
      CD56 expression can be used reliably to distinguish these entities. Myeloma
      associated osseous lesions and solitary plasmacytoma of bone showed myeloma-like
      immunophenotypes. However, some extramedullary plasmacytomas showed lymphoma-like
      phenotypes, suggesting that, in reality, they may represent non-Hodgkin lymphomas
      with extensive plasmacytic differentiation.

PMID- 17210523
TI  - Prevalence of thalassemia in patients with microcytosis referred for
      hemoglobinopathy investigation in Ontario: a prospective cohort study.
AB  - In Ontario, Canada, beta-thalassemia is easily detected through measurement of
      hemoglobin A2, but most laboratories do not do exhaustive DNA investigations for
      alpha-thalassemia. Therefore, the prevalence of thalassemia in microcytic samples
      for hemoglobinopathy investigation in Ontario is unknown. To address this, we
      performed a prospective cohort study in which samples referred for
      hemoglobinopathy investigation were also evaluated for alpha-thalassemia by DNA
      testing. Of 800 samples submitted, 664 were evaluable. Of the 664 patients
      represented, 163 (24.5%) were beta-thalassemia major carriers, 68 (10.2%) were
      hemoglobin Bart's hydrops fetalis carriers and, in total, 361 (54.4%) had some
      form of thalassemia. We conclude that microcytosis due to thalassemia is common
      in Ontario and that major forms of thalassemia, including forms predisposing to
      hemoglobin Bart's hydrops fetalis and beta-thalassemia major, are frequent. This
      illustrates the importance of adequate prenatal and laboratory investigation for
      these abnormalities in Ontario and other similar multiethnic jurisdictions
      worldwide.

PMID- 17210524
TI  - Microsatellite instability is uncommon in lymphoepithelioma-like carcinoma of the
      lung.
AB  - Primary lymphoepithelioma-like carcinoma of the lung (LELC) shares some
      morphologic and clinical characteristics with malignancies associated with
      microsatellite instability (MSI). The aims of our study were to determine the MSI
      status in LELC and compare these findings with stage I non-small cell lung
      carcinoma (NSCLC) with marked lymphocytic host response (MLHR). We assessed MSI
      by a DNA-based polymerase chain reaction assay using mononucleotide (BAT25 and
      BAT26) and dinucleotide (D2S123, D5S346, and D17S250) repeats. MSI was detected
      in 2 (29%) of 7 LELC cases with only 1 marker (D17S250), and in 3 (19%) of 16
      NSCLC cases with MLHR with only 2 markers (1D2S123 and 2 D17S250). Loss of
      heterozygosity (LOH) was detected at 1 or 2 of 3 dinucleotide repeats in 11 NSCLC
      cases (69%) with MLHR and 3 LELC cases (43%) (P = .36). The overall frequencies
      of LOH in NSCLC with MLHR were 29% and 19% in LELC (P = .55). MSI is very
      uncommon in LELC, indicating that MSI is not an important event in carcinogenesis
      for this tumor subtype. The presence of LOH suggests a probable role of tumor
      suppressor genes in LELC carcinogenesis.

PMID- 17210525
TI  - Immunohistochemical analysis for cytokeratin 7, KIT, and PAX2: value in the
      differential diagnosis of chromophobe cell carcinoma.
AB  - Immunohistochemical staining for cytokeratin 7 (CK7), KIT, and PAX2 expression
      was performed on 91 renal neoplasms, 37 conventional (clear cell) renal cell
      carcinomas (CRCCs), 20 papillary RCCs (PRCCs), 11 chromophobe RCCs (ChCs), and 23
      oncocytomas, with available karyotypes. All ChCs, 19 PRCCs, 2 CRCCs, and 1
      oncocytoma were CK7+; all ChCs, 22 oncocytomas, 2 CRCCs, and no PRCCs expressed
      KIT; PAX2 was positive in 31 CRCCs, 17 PRCCs, 20 oncocytomas, and 1 ChC. The
      predominant expression profiles were as follows: CRCC, CK7-/KIT-/PAX2+ (26/37);
      PRCC, CK7+/KIT-/PAX2+ (17/20); ChC, CK7+/KIT+/PAX2- (10/11); and oncocytoma, CK7
      /KIT+/PAX2+ (19/23). Cytogenetic analysis showed that the sole PAX2+ ChC had a
      retained chromosome 10, and all ChCs with chromosome 10 loss were PAX2-. These
      results identify specific staining patterns of the 4 major histologic subtypes of
      renal neoplasms and raise the question of a relationship between chromosome 10
      loss and loss of PAX2 expression in ChC.

PMID- 17210526
TI  - Increased culture recovery of Zygomycetes under physiologic temperature
      conditions.
AB  - Poor recovery of Zygomycetes hyphae from tissue specimens may result from failure
      of current culture methods to mimic physiologic conditions found in hyphae-laden
      infected tissue. We describe the use of an in vitro model simulating Zygomycetes
      growth under necrotic or hypoxic tissue conditions. We preconditioned hyphae of
      clinical Zygomycetes isolates in flasks under anaerobic conditions using Ana
      Packs (Becton Dickinson Microbiology Systems, Sparks, MD) at 37 degrees C for 48
      hours, thus simulating in vivo growth in an infracted hypoxic lesion, and
      compared the recovery of paired inocula at 37 degrees C and 25 degrees C.
      Incubation of stock culture isolates at 37 degrees C resulted in significantly
      better culture recovery (about 10-fold) when compared with incubation at 25
      degrees C (P < .0001). In addition, we similarly evaluated 25, 291 consecutive
      clinical specimens. Among 41 specimens, the yield of Zygomycetes cultures
      incubated at 37 degrees C (23/41 [56%]) was significantly higher than that
      incubated at 25 degrees C (9/41 [22%]; P = .0001). Overall, we found that culture
      recovery was significantly (254%) enhanced at 37 degrees C.

PMID- 17210527
TI  - Flow cytometric immunophenotyping of plasmacytic neoplasms.

PMID- 17210528
TI  - The value of inking breast cores to reduce specimen mix-up.
AB  - Accidental switching of tissue specimens in the histology laboratory can result
      in significant medical error. We sought to evaluate inking breast core needle
      specimens as a method to reduce the chance of specimen mix-up. We sequentially
      inked 1,000 consecutive breast core specimens with 6 different colors. Review of
      the color of the ink revealed 3 discrepancies: 1 related to blocks being
      switched, 1 related to incorrect labeling, and 1 was a typographical error.
      Inking of breast core specimens is a simple, inexpensive, and effective way to
      help reduce the chance of specimen mix-up.

PMID- 17210529
TI  - The role of anti-endothelial cell antibody-mediated microvascular injury in the
      evolution of pulmonary fibrosis in the setting of collagen vascular disease.
AB  - We encountered 16 patients with connective tissue disease in whom pulmonary
      fibrosis developed. Routine light microscopic, ultrastructural, and direct
      immunofluorescent analyses were conducted, and circulating antibodies, including
      those of endothelial cell derivation, were assessed using indirect immuno
      fluorescence and Western blot assays. Underlying diseases were dermatomyositis,
      scleroderma, mixed connective tissue disease, sclerodermatomyositis, Sjogren
      syndrome, rheumatoid arthritis, and anti-Ro-associated systemic lupus
      erythematosus. Antibodies to one or more Ro, RNP, Jo 1, OJ, and/or nucleolar
      antigens were seen in all cases and antiphospholipid antibodies in half. All
      biopsies revealed microvascular injury in concert with intraparenchymal fibrosis;
      in some cases, there were corroborative ultrastructural findings of microvascular
      injury. Patterns of fibroplasia represented nonspecific interstitial pneumonitis
      and usual interstitial pneumonitis. We noted IgG, IgA, and/or complement in the
      septal microvasculature. In 6 cases with available serum samples, indirect
      immunofluorescent endothelial cell antibody studies were positive and Western
      Blot studies showed reactivity of serum samples to numerous endothelial cell
      lysate-derived proteins. Pulmonary fibrosis, a recognized complication of
      systemic connective tissue disease, develops in connective tissue disease
      syndromes with pathogenetically established immune-based microvascular injury at
      other sites. A similar mechanism of antibody-mediated endothelial cell injury may
      be the basis of the tissue injury and fibrosing reparative response.

PMID- 17210530
TI  - Focus floating microscopy: "gold standard" for cutaneous borreliosis?
AB  - Borrelia burgdorferi is difficult to detect in routine biopsy material from
      patients with skin lesions of borreliosis. In this study, a new
      immunohistochemical method, focus floating microscopy (FFM), was developed to
      detect B burgdorferi in tissue sections and was compared with polymerase chain
      reaction (PCR). By using standard histologic equipment, tissue sections stained
      with a polyclonal B burgdorferi antibody were simultaneously scanned through 2
      planes: horizontally in serpentines and vertically by focusing through the
      thickness of the section. Borrelia were detected in 47 of 71 ticks, 34 of 66 tick
      bites, 30 of 32 erythema chronicum migrans cases, 41 of 43 borrelial
      lymphocytomas, and 50 of 51 acrodermatitis chronica atrophicans cases. FFM proved
      to be more sensitive than PCR (96.0% vs 45.2%) and nearly equally specific (99.4%
      vs 100%). All 169 control cases, except 1 false-positive case of secondary
      syphilis, were negative with FFM. FFM is an easy, quick, and inexpensive method
      to reliably detect Borrelia in cutaneous tissue sections.

PMID- 17210531
TI  - Comparative analysis of flow cytometric techniques in assessment of ZAP-70
      expression in relation to IgVH mutational status in chronic lymphocytic leukemia.
AB  - We compared 1 subjective and 5 objective flow cytometric methods to evaluate zeta
      associated protein (ZAP-70) expression in relation to immunoglobulin heavy-chain
      variable-region (IgVH) gene mutational status in 154 samples from 125 patients
      with chronic lymphocytic leukemia (CLL). ZAP-70 expression determined by all
      methods used correlated with IgVH gene mutational status, but none of them
      demonstrated high concordance rates. Of the objective methods, ZAP-70 staining
      determined as a ratio of molecules of equivalent soluble fluorochrome intensity
      in CLL cells to that in normal B cells (ZAP-70+ staining in IgVH germline cases,
      59%; ZAP-70- in IgVH mutated cases, 75%) or T cells (ZAP-70+ in IgVH germline
      cases, 66%; ZAP-70- in IgVH mutated cases, 57%) provides the best combination for
      assigning ZAP-70+ status to IgVH germline and ZAP-70- status to IgVH mutated
      cases. The subjective method based on ZAP-70 expression in natural killer/T cells
      gave a similar result, but reproducibility between laboratories may be difficult.
      Further studies on ZAP-70 expression in relation to clinical parameters may
      address whether ZAP-70 is an independent prognostic marker for CLL.

PMID- 17210533
TI  - The impact of religiousness, spirituality, and social support on psychological
      well-being among older adults in rural areas.
AB  - This paper presents the results of a study on the impact of spirituality,
      religiousness, and social support on the psychological well-being among rural
      elderly. With a rural community sample of 215 older adults, hierarchical
      regression analyses found significant associations between dimensions of
      spirituality/religiousness, social support, and psychological well-being, with
      spirituality/religiousness inversely related to depression and social support,
      positively related to life satisfaction. Findings of this study suggest that
      practitioners need to develop programs or services that are congruent with
      religious/spiritual beliefs and practices in order to better enhance the
      psychosocial well-being and improve the quality of life among older persons in
      rural areas.

PMID- 17210532
TI  - Vaccination and the dynamics of immune evasion.
AB  - Vaccines exert strong selective pressures on pathogens, favouring the spread of
      antigenic variants. We propose a simple mathematical model to investigate the
      dynamics of a novel pathogenic strain that emerges in a population where a
      previous strain is maintained at low endemic level by a vaccine. We compare three
      methods to assess the ability of the novel strain to invade and persist:
      algebraic rate of invasion; deterministic dynamics; and stochastic dynamics.
      These three techniques provide complementary predictions on the fate of the
      system. In particular, we emphasize the importance of stochastic simulations,
      which account for the possibility of extinctions of either strain. More
      specifically, our model suggests that the probability of persistence of an
      invasive strain (i) can be minimized for intermediate levels of vaccine cross
      protection (i.e. immune protection against the novel strain) and (ii) is lower if
      cross-immunity acts through a reduced infectious period rather than through
      reduced susceptibility.

PMID- 17210534
TI  - Spirit of aging rising: cross-cutting thematic modules to enrich foundation
      graduate social work courses.
AB  - To enrich an urban generalist MSW program serving a diverse aging community, an
      innovative approach was initiated. A team of students, faculty and a field
      instructor collaborated in creating and evaluating 3 sets of cross-cutting
      thematic modules. An overview of the thematic modules (addressing elder abuse,
      family caregiving, and mental health), integrated across multiple curriculum
      areas (Human Behavior and the Social Environment, Macro/Policy, Practice and
      Research), is presented along with results of a faculty focus group evaluating
      the process of coordinating module content for one full week of class per
      foundation area (one topic per quarter).

PMID- 17210535
TI  - A dual process model of grief counseling: findings from the Changing Lives of
      Older Couples (CLOC) study.
AB  - This paper tests Stroebe and Schut's Dual Process Model of Bereavement using data
      from the Changing Lives of Older Couples (CLOC), a prospective study of 1,532
      married persons over the age of 65. This analysis focused on a weighted sample of
      104 widowers and 492 widows at six months, 18 months, and four years later.
      Bradburn's Affect Balance Scale was used as the dependent variable, and the
      independent variables were based on Stroebe and Schut's bereavement model. The
      multiple regression analyses revealed that loss- and restoration-oriented
      activities were important throughout bereavement. Implications for bereavement
      counseling are discussed.

PMID- 17210536
TI  - Spiritual assessment in aging: a framework for clinicians.
AB  - Older adults may benefit from clinical conversations about the role of
      spirituality in their lives, but social workers and other helping professionals
      often do not have an understanding of where to proceed beyond initial questions
      of whether spirituality and/or religion are important and if so, what religious
      preference is held. Much has been written about definitions of spirituality and
      religion, but the literature has not yet provided a clear focus on ways to assess
      whether these are integrated positively or negatively in the lives of older
      adults. This article identifies eleven domains in spirituality that might be
      assessed. Within each domain an explanation is provided as well as a brief
      discussion of the rationale for including it in the classification. Sample
      interview questions and an illustrative vignette are included. Together these
      eleven domains build an important framework and resource for spiritual assessment
      with older adults.

PMID- 17210537
TI  - Providing mental health services to older people living in rural communities.
AB  - Rural dwelling elders who experience mental health problems often have difficulty
      finding help since rural communities often lack adequate mental health service
      providers. This paper reports on the initial phase of a 5-year, interdisciplinary
      clinical research study that is testing the effectiveness of providing a home
      delivered, therapeutic psychosocial intervention, aimed at improving the
      emotional wellbeing and the quality of life of medically frail elders who live in
      rural communities. In the early phases of this study, the clinical research team
      encountered a number of interesting and often unanticipated challenges as it
      attempted to recruit study participants and provide services to them. In this
      article, we examine these challenges and share what we have learned so far about
      providing mental health services to elderly persons living in rural environments.

PMID- 17210538
TI  - Using collaboration to maximize outcomes for a John A. Hartford Foundation
      geriatric enrichment project.
AB  - Two institutions representing two BSW and one MSW program and a geriatric
      education center collaborated in a John A. Hartford geriatric enrichment project.
      Sharing the risks and benefits of a collaborative model, 75 percent of faculty
      participated in mini faculty fellowships, and bi-monthly dinner meetings with
      colleagues from each of the three programs, and actively engaged in the curricula
      revisions. Faculty report pervasive geriatric enrichment in each program's
      foundation content areas, and increases in students placed in geriatric enriched
      field practicum settings, from pre-project levels of 8.1 percent to a high of 24
      percent. The features of the collaborative project include: respecting each
      program's autonomy while actively sharing ideas, resources and partnering with
      community's aging experts; and strengthening mutually reciprocal relationships
      among faculty and the gerontologic practice community. This model of shared risks
      and benefits also provides opportunities for innovation, diverse thinking, and
      shared decision making.

PMID- 17210539
TI  - Bringing the community in: partnerships for aging enrichment.
AB  - Aging enrichment of undergraduate social work curricula ensures that program
      graduates will be prepared to practice with older adults. This article reports
      the results of focus group research that was designed to engage social workers
      from community agencies serving older adults in preparing students to become
      "aging-savvy" social workers. The workers highlighted the importance of wide
      ranging exposure to older adults, the changing needs of older adults, and the
      importance of increasing students' comfort with self-determination. These
      findings informed the program's ongoing curricular transformation process through
      the incorporation of new assignments that enabled increased contact with older
      adults in a variety of settings.

PMID- 17210540
TI  - Preparing social work students to work with grandparents in kinship care: an
      approach to infusion of content materials into selected core social work courses.
AB  - Grandparents in kinship care represent an expanding population of older adults
      assuming primary parenting responsibilities for their grandchildren at a time
      when many grandparents may also be experiencing developmental changes
      accompanying their own aging process. Research documents a lack of social workers
      prepared to respond to the needs of an aging population in general, and
      grandparents in kinship care in particular, as curricular content on this
      population has been limited in undergraduate and graduate social work programs.
      This article describes an infusion model proposed for an undergraduate social
      work program's GeroRich Project designed to introduce content on an aging
      population in four foundation courses to expand students' knowledge of older
      adults and grandparents as kinship care providers.

PMID- 17210541
TI  - Joy of living: a community-based mental health promotion program for African
      American elders.
AB  - African American elders are often acknowledged for their resilience in overcoming
      discrimination. Because of their unique historical experience, many have relied
      upon family support and spirituality to address mental health problems and have
      shunned professional mental health services. Despite the strengths of African
      American elders, there are mental health needs that require professional
      intervention. This article specifically discusses a mental health promotion
      program sponsored by the Mental Health Association of the District of Columbia.
      It provides a description of the program and an evaluation of its outcomes. An
      analysis of pre and post intervention evaluations (n = 228) shows success of the
      intervention in raising participant awareness of normal and abnormal mental
      health as well as resources available to them.

PMID- 17210543
TI  - Listening to seniors: successful approaches to data collection and program
      development.
AB  - This paper provides guidelines for high quality data collection with community
      residing older adults with illustrations drawn from the authors' practice. A
      mixed-method approach is described as a means to obtain the highest quality
      information from the sample. This approach combines focus groups and interviews
      along with mailed, closed-ended surveys to access both the "depth" of the
      seniors' responses as well as the "breadth" of responses; that is, the
      qualitative aspects provide the opportunity to identify and define relevant
      issues in the voices of respondents, while mailed surveys provide the kind of
      coverage necessary to make accurate predictions to the larger population of
      community-residing seniors.

PMID- 17210542
TI  - Filipinas as residential long-term care providers: influence of cultural values,
      structural inequity, and immigrant status on choosing this work.
AB  - This exploratory study investigated reasons why Filipinas in Hawai'i have become
      the primary caregivers of elders in residential care homes and if they thought
      their children would follow them in this profession. A random sample of 173
      Filipina care home operators (CHO), of which 95% were first-generation
      immigrants, was interviewed using telephone survey methods. Data were collected:
      to profile caregivers; to identify motivations for becoming a care home operator;
      and to gauge if they or their children would continue in this line of work. The
      sample was composed of middle-aged Filipina CHO with training and experience in
      elder care who concurred that the job fit their cultural values. About a third
      also felt that this job was open to immigrants and helped them buy a house.
      Twenty percent or less felt discriminated against because of this work. Although
      half the sample felt that women were better caregivers than men, only 38% felt
      that caregiving was primarily the responsibility of women. Almost 90% planned to
      continue with this work, but only 12% said it was likely that their children or
      grandchildren would become CHO, supporting the notion that choosing this
      profession had less to do with cultural values and gender expectations than with
      economic opportunities available to the current cohort of CHO. Given these
      findings, Hawai'i's capacity to meet future residential long-term care needs is
      discussed.

PMID- 17210544
TI  - Mosaic of difference: enhancing culturally competent aging-related knowledge
      among social workers.
AB  - The professional literature has not adequately addressed the behavioral and
      social factors that contribute to different coping outcomes for African American
      elder caregivers as compared to non African Americans. Awareness and
      understanding of these unique experiences would better prepare professionals to
      work with such clients. This study examines the predictors of emotional distress
      among 46 African American women who provide care to dependent elderly parents.
      Multivariate statistical analyses show that elder caregivers' rating of quality
      of life, their years of caregiving, as well are their poor heath constitute
      significant predictors of risk for depression. The results of the study provide
      support for the inclusion of more culturally appropriate measures of caregiver
      distress, and provide insights to inform social work practice, policy and
      research concerning African American female elder caregivers in the 21st century.

PMID- 17210545
TI  - Medical librarian 2.0.
AB  - Web 2.0 refers to an emerging social environment that uses various tools to
      create, aggregate, and share dynamic content in ways that are more creative and
      interactive than transactions previously conducted on the Internet. The extension
      of this social environment to libraries, sometimes called Library 2.0, has
      profound implications for how librarians will work, collaborate, and deliver
      content. Medical librarians can connect with present and future generations of
      users by learning more about the social dynamics of Web 2.0's vast ecosystem, and
      incorporating some of its interactive tools and technologies (tagging, peer
      production, and syndication) into routine library practice. doi:
      10.1300/J115v26n01_01.

PMID- 17210546
TI  - Podcasting at the University of Virginia Claude Moore Health Sciences Library.
AB  - The Claude Moore Health Sciences Library co-sponsors a History of the Health
      Sciences Lecture Series in the fall and spring of each year. Each lecture is
      produced and recorded for the benefit of the University of Virginia Heath System
      and members of the surrounding community. In the fall of 2005, the Library
      decided to begin podcasting the lectures via the Internet. This article describes
      the investigation process for creating access to the content via podcast,
      Webcast, and direct download. The article also addresses how the Library is
      teaching podcasting in its annual Multimedia Bootcamp and exploring additional
      uses for podcasting. doi:10.1300/J115v26n01_02.

PMID- 17210547
TI  - Integrating and promoting medical podcasts into the library collection.
AB  - Podcasts offer a way for medical professionals to listen to current information
      in medicine from an iPod, MP3 player, handheld device, or computer. As podcasts
      become more popular, libraries may be interested in integrating programs into the
      library collection. South Pointe Medical Library evaluated medical podcasts
      relevant to the scope of the library collection and explored methods for finding
      and organizing such programs in ways that are efficient for both the librarian
      and the patron. doi:10.1300/J115v26n01_03.

PMID- 17210548
TI  - RSS made easy: a basic guide for librarians.
AB  - Really Simple Syndication (RSS) uses extensive markup language (XML) to
      constantly scan the content of Web sites for updates, which will then be
      delivered to subscribers' desktops or mobile devices through an RSS feed. RSS
      helps professionals stay current while reducing workloads. Librarians need to get
      familiar with RSS to educate their users, to stay current in information
      technology, and to generate and disseminate selected information to target user
      groups. doi:10.1300/J115v26n01_04.

PMID- 17210549
TI  - LactMed-new NLM database on drugs and lactation.
AB  - LactMed, released in the spring of 2006, is a new peer-reviewed database from the
      Specialized Information Services division of the National Library of Medicine
      that is accessible free of charge through the TOXNET suite of databases. As its
      name indicates, Lact- Med provides information on medicines used during lactation
      along with data on the levels of these drugs in breast milk and infant blood, the
      potential effects on the breastfed infants, and possible alternatives to these
      drugs. doi:10.1300/J115v26n01_05.

PMID- 17210550
TI  - Tracking avian flu on the Web.
AB  - To some the term avian flu or H5N1 has become synonymous with the pandemic flu of
      1918. Like the former pandemic, this current threat has the potential to cause up
      to 7.4 million deaths worldwide. Yet as of mid-2006, the viability of this threat
      is still unclear. There is no doubt that birds, especially poultry, have been the
      primary target of this particular strain of influenza. Human illnesses and deaths
      have resulted from direct contact with birds; farmers and food handlers are most
      at risk. Fortunately there has not been a shift to human-to-human transmission.
      However, it is imperative for public heath officers, health professionals, and
      other appropriate officials to keep current on the progress of this virus within
      the bird population, and its spread around the world. Preventative measures
      including worst case scenarios have been widely discussed and even resulted in a
      made-for-TV movie. The need for up-to-date information is essential in order to
      track the extent of transmission, location of current outbreaks, and most
      importantly steps for preparedness that could be vital for prevention and
      containment. This article explores and identifies major Web sites along with
      basic Internet search techniques to find informative and credible Webbased
      resources. doi:10.1300/J115v26n01_06.

PMID- 17210551
TI  - Serving our colleagues: reference and history of medicine services from the
      National Library of Medicine.
AB  - Most biomedical librarians are frequent users of the major online services
      provided by the National Library of Medicine (NLM), part of the National
      Institutes of Health in Bethesda, Maryland. These services include
      MEDLINE/PubMed, MedlinePlus, ClinicalTrials.gov, PubMed Central, document
      delivery, and other key biomedical resources. This article highlights less well
      known services from reference, to historical information, to training and other
      services which librarians may not be aware the NLM offers to them. NLM encourages
      librarians to consider that NLM's unique and unsurpassed collection can help when
      local resources may be too limited to serve the needs of their patrons.
      doi:10.1300/J115v26n01_07.

PMID- 17210552
TI  - Livening up the classroom: using audience response systems to promote active
      learning.
AB  - Audience response system (ARS) technology offers considerable promise for
      bringing more interactivity and engagement to the classroom. Since gaining
      momentum in the late 1990s, ARS use has been promoted for its ability to provide
      immediate feedback, focus student attention, identify gaps in knowledge, and
      enhance student involvement. This inexpensive technology is potentially of great
      value for improving the educational experience of students and instructors alike.
      doi:10.1300/J115v26n01_08.

PMID- 17210556
TI  - The research pendulum: multiple roles and responsibilities as a researcher.
AB  - Qualitative research on sexual identities has highlighted the use of oral
      narratives to understand the lives of lesbians and gay men. Feminist
      ethnographers, sociologists and queer theorists have further posed methodological
      inquiries to the issues of insider/outsider, the possibilities of an erotic
      subject and the matter of representation. Using interview data with Hong Kong
      lesbians, this paper discusses a researcher's multiple positionalities and its
      effects on both the researched and the researcher. Being self-reflexive requires
      a researcher to test her or his own boundaries and to take up social
      responsibilities as the interpreter of texts. This paper calls for further
      dialogue between a researcher's subject positions, research processes and the
      final presentation of findings. doi:10.1300/J155v10n03_02.

PMID- 17210557
TI  - Beyond identity politics: the making of an oral history of Hong Kong women who
      love women.
AB  - Oral history has long been an important resource for lesbian and other
      underprivileged groups in advancing identity politics. While there is an
      increased awareness of social construction of identity and the impact of race and
      class on the experiences of sexual identities, oral historians have yet to
      rethink their task in view of poststructuralists' and queer theorists' critique
      of identity. This paper examines the "Oral History Project of Hong Kong Women Who
      Love Women" as an attempt to construct histories that respect difference and
      minimize normalization. It discusses the project's significance in terms of its
      subversion of the heterosexual/homosexual binary and its queering of the notions
      of identity, community and coming out. The critique unfolded is one of anti
      assimilation and anti-minoritization. doi:10.1300/J155v10n03_03.

PMID- 17210558
TI  - Beyond pain and protection: politics of identity and iban girls in Korea.
AB  - This study analyzes the complexities in the exploration of iban girls' identities
      and the various ways how girls appropriate varied sources such as popular culture
      to examine the heterogeneousness of identity explorations and rethink the
      politics of identities. Against the tendency in current discourse on homosexual
      youth in Korea, protection discourse and pain discourse, the notion of identity
      itself will be critically examined and the girls' agency in destabilizing
      heteronormativity will be discussed. This study also deals with the appropriation
      of popular culture by the girls, suggesting that cultural critiques should reveal
      complex dynamics in concrete experiences. doi:10.1300/J155v10n03_04.

PMID- 17210559
TI  - The politics of "disregarding": addressing Zainichi issues within the lesbian
      community in Japan.
AB  - This article discusses the difference in positionality between Japanese lesbians
      and Zainichi (literally, "resident in Japan") Korean lesbians. The author first
      presents a narrative written by a Zainichi Korean lesbian, in which she expresses
      her anger toward Japanese lesbians. Setting her narrative as a starting point,
      the author retraces the controversial incident that occurred during the second
      Asian Lesbian Network (ALN) conference that was held in Japan in 1992. Through a
      re-reading of a series of narratives with regard to the second conference, the
      author demonstrates how the unequal power relations between Japanese lesbians and
      Zainichi Korean lesbians operate in what she calls the politics of
      "disregarding," where Zainichi Korean lesbians are continuously omitted from the
      consciousness of Japanese lesbians. doi:10.1300/ J155v10n03_05.

PMID- 17210560
TI  - Noras on the road: family and marriage of lesbian women in Shanghai.
AB  - During the past decade, we have witnessed the rise of Shanghai as a new
      metropolitan centre in China. The city has also become one of the most vibrant
      sites of lesbian community in the country. The author interviewed 20 lesbian
      women in the city in 2005. It is found that almost all of the women interviewed
      are experiencing the pressure of social conformity most severely from their
      immediate family, and the social expectation of marriage. In this paper, the
      author demonstrates the conflicts of family and marriage that many of the
      informants have encountered and how the hegemony of heterosexuality is still
      securely reproduced and carried out through the discourses of family and marriage
      in contemporary urban China, and finally, how the informants deal with the
      controls enacted by the institution of heterosexuality. doi:10.1300/
      J155v10n03_06.

PMID- 17210561
TI  - Lesbian mothers in Japan: an insider's report.
AB  - This report introduces Remaza-Kansai, a lesbian mother group in Japan based in
      the Kansai area, their activities, and the lives of some of the participants in
      the activities based on interviews by the author. Remaza-Kansai organizes
      activities and special events for lesbian mothers and their children. It also
      manages a website and operates a bulletin board for lesbian mothers. In the
      interviews, it is found that besides the lack of legal recognition of lesbian
      mothers not biologically connected to the children, they also experience
      difficulties relating to schools. Another issue requiring further inquiry is how
      lesbian mothers "come out" to their children. doi:10.1300/J155v10n03_07.

PMID- 17210563
TI  - Lesbian discourses in mainstream magazines of post-war Japan: is onabe distinct
      from rezubian?
AB  - This paper elucidates the changes in the meanings associated with the term
      rezubian (the Japanese term for "lesbian") through an analysis of its discourse
      in magazines for general readership published in post-war Japan. The category of
      "rezubian" first appeared in mainstream magazines in the 1960s as a generic
      category that referred to both "masculinized women" and "women who engage in
      sexual acts with other women." Masculinized women, in particular, were called
      "onabe." At first "onabe" denoted "a tachi rezubian," meaning a lesbian who plays
      "top," but gradually a distinction came to be made between "rezubian who are
      onabe" and "rezubian who aren't." The early 1990s saw the differentiation of
      "onabe" as a category distinct from that of "rezubian." Focusing particularly on
      this process of differentiation, this paper traces the transitions in the
      signifying practices pertaining to the category rezubian.
      doi:10.1300/J155v10n03_09.

PMID- 17210562
TI  - Lesbians in China's mainland: a brief introduction.
AB  - This paper describes and introduces lesbians' lives and the relevant research in
      China's Mainland. The first part shows the slow development of lesbian culture in
      the form of literature, films and documentaries. Although lesbians' lives were
      reflected more or less in modern literature, the "true" lesbian novel was
      published only recently. Relevant films and documentaries were never shown to the
      public in China. Lesbian culture is still unevenly developed and remains
      negligible. The first part also describes lesbian research in the field of
      literature, psychiatry and sociology. The relevant research in literature is
      relatively systematic and rich, while that in psychiatry is fraught with
      discrimination and that in sociology is relatively weak. The second part presents
      the observation and analysis of lesbian Internet communities. It deals with
      lesbians' self-identity, role differentiation, sentiments and sexuality. Among
      them, role differentiation plays an important part in lesbians' lives though few
      researchers have studied it. Most lesbian organizations founded on the strength
      of Internet communication lack experience and resources and have little influence
      on the masses. Some lesbians are accepted by the public, but in return, they
      compromise to some popular values. This is extremely disadvantageous to those who
      are unwilling to give in. At the end of the paper, the first author expresses her
      future plan that she will continue her study on lesbian culture under the help of
      Internet observation and various activities. doi:10.1300/J155v10n03_08.

PMID- 17210564
TI  - Possibilities and limitations of "lesbian continuum": the case of a protestant
      church in Japan.
AB  - "Lesbian existence" is still invisible in Japanese society, although Japan is
      portrayed as being "tolerant" toward homosexuality. However, there is strong
      activism that tries to make lesbians visible. An example is Christian women's
      activism against homophobic discourses in the United Church of Christ in Japan
      (UCCJ/Kyodan) which is a denomination of Protestant Churches in Japan. This case
      helps us analyse the positionality of lesbians in the discourses of Christianity
      in a non-Christian society, Japan. Introduced to English-speaking audiences for
      the first time, this case shows clearly that the forces which produce the
      exclusion of lesbians and gays do not only have a religious origin but also a
      social background. This particular religious-social context sets the gay men as
      the object of discrimination but brings forth resistance activism by women
      lesbians, bisexuals, and heterosexuals. Such women's activism against homophobia
      is analyzed as an example of the "lesbian continuum" (Adrienne Rich) and the
      possibilities and limitations of the continuum are explored.
      doi:10.1300/J155v10n03_10.

PMID- 17210565
TI  - The lesbian rights movement and feminism in South Korea.
AB  - The lesbians' rights movement in South Korea has undertaken various projects for
      solidarity with feminist movement groups for over 10 years. In spite of these
      efforts, lesbian issues have been blatantly excluded from all the agendas of
      women's rights. The same thing has happened in Women's Studies. Some feminists
      express homophobic thoughts without understanding the reality of lesbians, and
      other young scholars take on a lesbian identity temporarily as a sign of being
      progressive and liberated; in neither situation are they committed to dealing
      with the oppression of lesbians or seeing lesbian rights as a feminist concern.
      In order to further lesbian rights there are two strategies possible: forming a
      movement only for lesbians or forming solidarity with feminists. In the latter
      case, a concern about lesbian rights will help achieve the goals of a true
      feminism as patriarchy is built upon heterosexism. doi:10.1300/J155v10n03_11.

PMID- 17210567
TI  - How ATP hydrolysis controls filament assembly from profilin-actin: implication
      for formin processivity.
AB  - Formins catalyze rapid filament growth from profilin-actin, by remaining
      processively bound to the elongating barbed end. The sequence of elementary
      reactions that describe filament assembly from profilin-actin at either free or
      formin-bound barbed ends is not fully understood. Specifically, the identity of
      the transitory complexes between profilin and actin terminal subunits is not
      known; and whether ATP hydrolysis is directly or indirectly coupled to profilin
      actin assembly is not clear. We have analyzed the effect of profilin on actin
      assembly at free and FH1-FH2-bound barbed ends in the presence of ADP and non
      hydrolyzable CrATP. Profilin blocked filament growth by capping the barbed ends
      in ADP and CrATP/ADP-Pi states, with a higher affinity when formin is bound. We
      confirm that, in contrast, profilin accelerates depolymerization of ADP-F-actin,
      more efficiently when FH1-FH2 is bound to barbed ends. To reconcile these data
      with effective barbed end assembly from profilin-MgATP-actin, the nature of
      nucleotide bound to both terminal and subterminal subunits must be considered.
      All data are accounted for quantitatively by a model in which a barbed end whose
      two terminal subunits consist of profilin-ATP-actin cannot grow until ATP has
      been hydrolyzed and Pi released from the penultimate subunit, thus promoting the
      release of profilin and allowing further elongation. Formin does not change the
      activity of profilin but simply uses it for its processive walk at barbed ends.
      Finally, if profilin release from actin is prevented by a chemical cross-link,
      formin processivity is abolished.

PMID- 17210568
TI  - The p38alpha/beta mitogen-activated protein kinases mediate recruitment of CREB
      binding protein to preserve fast myosin heavy chain IId/x gene activity in
      myotubes.
AB  - In skeletal muscle, the transformation of fast into slow fiber type is
      accompanied by shifts in fiber type-specific gene expression that includes down
      regulation of the adult fast fiber myosin heavy chain IId/x (MyHCIId/x) gene.
      Here, we report that the mitogen-activated protein kinases (MAPKs) p38alpha/beta
      regulate MyHCIId/x gene expression. Electrical stimulation of rabbit skeletal
      muscle cells with a slow fiber type activity pattern and treatment of C2C12
      myotubes with Ca(2+)-ionophore inhibited p38alpha/beta MAPKs and reduced fast
      fiber type MyHC protein expression and promoter activity. Pharmacological
      inhibition of p38alpha/beta also down-regulated MyHCII gene expression. In
      controls, binding of the myocyte enhancer factor-2 (MEF-2) isoforms C and D as a
      heterodimer to a proximal consensus site within the MyHCIId/x promoter and
      recruitment of a transcriptional coactivator, the CREB-binding protein CBP, were
      observed. Overexpression of wild type MEF-2C but not of a MEF-2C mutant that
      cannot be phosphorylated by p38 induced promoter activity. Mutation of the MEF-2
      binding site decreased the inducing effect of overexpressed CBP. Inhibition of
      p38alpha/beta MAPKs abolished CBP binding, whereas enforced induction of p38 by
      activated MAPK kinase 6 (MKK6EE) enhanced binding of CBP and increased promoter
      activity. Furthermore, knockdown of endogenous CBP by RNA interference eliminated
      promoter activation by MEF-2C or MKK6EE. In electrical stimulated and Ca(2+)
      ionophore-treated myotubes, CBP was absent in complex formation at that site.
      Taken together, the data indicate that p38alpha/beta MAPKs-mediated coactivator
      recruitment at a proximal MEF-2 site is important for MyHCIId/x gene regulation
      in skeletal muscle.

PMID- 17210569
TI  - The Coxsackie and adenovirus receptor binds microtubules and plays a role in cell
      migration.
AB  - The Coxsackie and adenovirus receptor (CAR), a cell adhesion molecule of the
      immunoglobulin superfamily, inhibits cell growth of a variety of tumors. The
      cytoplasmic domain of CAR has been implicated in decreased invasion and
      intracerebral growth of human U87 glioma cells. Using affinity binding, we
      identified tubulin as an interaction partner for the cytoplasmic domain of CAR.
      The interaction was specific; CAR and tubulin co-immunoprecipitated in cells
      expressing endogenous CAR and partially co-localized in situ. The binding of CAR
      to tubulin heterodimers and to microtubules was direct, with dissociation
      constants of approximately 1 mum for tubulin and approximately 32 nm for in vitro
      assembled microtubules. Whereas CAR-expressing U87 glioma cells had decreased
      migration in a chemotactic assay in Boyden chambers as compared with control
      cells, an effect that depended on the presence of the cytoplasmic domain of CAR,
      the difference was abrogated at low, non-cytotoxic doses of the taxane
      paclitaxel, a microtubule-stabilizing agent. These results indicate that CAR may
      affect cell migration through its interaction with microtubules.

PMID- 17210570
TI  - Dual role of platelet protein kinase C in thrombus formation: stimulation of pro
      aggregatory and suppression of procoagulant activity in platelets.
AB  - Protein kinase C (PKC) isoforms regulate many platelet responses in a still
      incompletely understood manner. Here we investigated the roles of PKC in the
      platelet reactions implicated in thrombus formation as follows: secretion
      aggregate formation and coagulation-stimulating activity, using inhibitors with
      proven activity in plasma. In human and mouse platelets, PKC regulated
      aggregation by mediating secretion and contributing to alphaIIbbeta3 activation.
      Strikingly, PKC suppressed Ca(2+) signal generation and Ca(2+)-dependent exposure
      of procoagulant phosphatidylserine. Furthermore, under coagulant conditions, PKC
      suppressed the thrombin-generating capacity of platelets. In flowing human and
      mouse blood, PKC contributed to platelet adhesion and controlled secretion
      dependent thrombus formation, whereas it down-regulated Ca(2+) signaling and
      procoagulant activity. In murine platelets lacking G(q)alpha, where secretion
      reactions were reduced in comparison with wild type mice, PKC still positively
      regulated platelet aggregation and down-regulated procoagulant activity. We
      conclude that platelet PKC isoforms have a dual controlling role in thrombus
      formation as follows: (i) by mediating secretion and integrin activation required
      for platelet aggregation under flow, and (ii) by suppressing Ca(2+)-dependent
      phosphatidylserine exposure, and consequently thrombin generation and
      coagulation. This platelet signaling protein is the first one identified to
      balance the pro-aggregatory and procoagulant functions of thrombi.

PMID- 17210571
TI  - Mechanism of abasic lesion bypass catalyzed by a Y-family DNA polymerase.
AB  - The 3 million-base pair genome of Sulfolobus solfataricus likely undergoes
      depurination/depyrimidination frequently in vivo. These unrepaired abasic lesions
      are expected to be bypassed by Dpo4, the only Y-family DNA polymerase from S.
      solfataricus. Interestingly, these error-prone Y-family enzymes have been shown
      to be physiologically vital in reducing the potentially negative consequences of
      DNA damage while paradoxically promoting carcinogenesis. Here we used Dpo4 as a
      model Y-family polymerase to establish the mechanistic basis for DNA lesion
      bypass. While showing efficient bypass, Dpo4 paused when incorporating
      nucleotides directly opposite and one position downstream from an abasic lesion
      because of a drop of several orders of magnitude in catalytic efficiency.
      Moreover, in disagreement with a previous structural report, Dpo4-catalyzed
      abasic bypass involves robust competition between the A-rule and the lesion loop
      out mechanism and is governed by the local DNA sequence. Analysis of the strong
      pause sites revealed biphasic kinetics for incorporation indicating that Dpo4
      primarily formed a nonproductive complex with DNA that converted slowly to a
      productive complex. These strong pause sites are mutational hot spots with the
      embedded lesion even affecting the efficiency of five to six downstream
      incorporations. Our results suggest that abasic lesion bypass requires tight
      regulation to maintain genomic stability.

PMID- 17210572
TI  - A function for the psi subunit in loading the Escherichia coli DNA polymerase
      sliding clamp.
AB  - Crystal structures of an Escherichia coli clamp loader have provided insight into
      the mechanism by which this molecular machine assembles ring-shaped sliding
      clamps onto DNA. The contributions made to the clamp loading reaction by two
      subunits, chi and psi, which are not present in the crystal structures, were
      determined by measuring the activities of three forms of the clamp loader,
      gamma(3)deltadelta', gamma(3)deltadelta'psi, and gamma(3)deltadelta'psichi. The
      psi subunit is important for stabilizing an ATP-induced conformational state with
      high affinity for DNA, whereas the chi subunit does not contribute directly to
      clamp loading in our assays lacking single-stranded DNA-binding protein. The psi
      subunit also increases the affinity of the clamp loader for the clamp in assays
      in which ATPgammaS is substituted for ATP. Interestingly, the affinity of the
      gamma(3)deltadelta' complex for beta is no greater in the presence than in the
      absence of ATPgammaS. A role for psi in stabilizing or promoting ATP- and
      ATPgammaS-induced conformational changes may explain why large conformational
      differences were not seen in gamma(3)deltadelta' structures with and without
      bound ATPgammaS. The beta clamp partially compensates for the activity of psi
      when this subunit is not present and possibly serves as a scaffold on which the
      clamp loader adopts the appropriate conformation for DNA binding and clamp
      loading. Results from our work and others suggest that the psi subunit may
      introduce a temporal order to the clamp loading reaction in which clamp binding
      precedes DNA binding.

PMID- 17210573
TI  - Concentrative export from the endoplasmic reticulum of the gamma-aminobutyric
      acid transporter 1 requires binding to SEC24D.
AB  - Re-uptake of gamma-aminobutyric acid (GABA) into presynaptic specializations is
      mediated by the GABA transporter 1 (GAT1), a member of the SLC6 gene family.
      Here, we show that a motif in the COOH terminus of GAT1 ((566)RL(567)), which is
      conserved in SLC6 family members, is a binding site for the COPII coat component
      Sec24D. We also identified residues in Sec24D ((733)DD(734)) that are required to
      support the interaction with GAT1 and two additional family members, i.e. the
      transporters for serotonin and dopamine. We used three strategies to prevent
      recruitment of Sec24D to GAT1: knock-down of Sec24D by RNA interference,
      overexpression of Sec24D-VN (replacement of (733)DD(734) by (733)VN(734)), and
      mutation of (566)RL(567) to (566)AS(567) (GAT1-RL/AS). In each instance,
      endoplasmic reticulum (ER) export of GAT1 was impaired: in the absence of Sec24D
      or upon coexpression of dominant negative Sec24D-VN, GAT1 failed to undergo
      concentrative ER export; GAT1-RL/AS also accumulated in the ER and exerted a
      dominant negative effect on cell surface targeting of wild type GAT1. Our
      observations show that concentrative ER-export is contingent on a direct
      interaction of GAT1 with Sec24D; this also provides a mechanistic explanation for
      the finding that oligomeric assembly of transporters is required for their ER
      export: transporter oligomerization supports efficient recruitment of COPII
      components.

PMID- 17210574
TI  - Burst kinetics and redox transformations of the active site manganese ion in
      oxalate oxidase: implications for the catalytic mechanism.
AB  - Oxalate oxidase (EC 1.2.3.4) catalyzes the oxidative cleavage of oxalate to
      carbon dioxide and hydrogen peroxide. In this study, unusual nonstoichiometric
      burst kinetics of the steady state reaction were observed and analyzed in detail,
      revealing that a reversible inactivation process occurs during turnover,
      associated with a slow isomerization of the substrate complex. We have
      investigated the underlying molecular mechanism of this kinetic behavior by
      preparing recombinant barley oxalate oxidase in three distinct oxidation states
      (Mn(II), Mn(III), and Mn(IV)) and producing a nonglycosylated variant for
      detailed biochemical and spectroscopic characterization. Surprisingly, the fully
      reduced Mn(II) form, which represents the majority of the as-isolated native
      enzyme, lacks oxalate oxidase activity, but the activity is restored by oxidation
      of the metal center to either Mn(III) or Mn(IV) forms. All three oxidation states
      appear to interconvert under turnover conditions, and the steady state activity
      of the enzyme is determined by a balance between activation and inactivation
      processes. In O(2)-saturated buffer, a turnover-based redox modification of the
      enzyme forms a novel superoxidized mononuclear Mn(IV) biological complex. An
      oxalate activation role for the catalytic metal ion is proposed based on these
      results.

PMID- 17210575
TI  - Oligomerization of the human prion protein proceeds via a molten globule
      intermediate.
AB  - The conformational transition of the human prion protein from an alpha-helical to
      a beta-sheet-rich structure is believed to be the critical event in prion
      pathogenesis. The molecular mechanism of misfolding and the role of intermediate
      states during this transition remain poorly understood. To overcome the obstacle
      of insolubility of amyloid fibrils, we have studied a beta-sheet-rich misfolded
      isoform of the prion protein, the beta-oligomer, which shares some structural
      properties with amyloid, including partial proteinase resistance. We demonstrate
      here that the beta-oligomer can be studied by solution-state NMR spectroscopy and
      obtain insights into the misfolding mechanism via its transient monomeric
      precursor. It is often assumed that misfolding into beta-sheet-rich isoforms
      proceeds via a compatible precursor with a beta-sheet subunit structure. We show
      here, on the contrary, evidence for an almost natively alpha-helix-rich monomeric
      precursor state with molten globule characteristics, converting in vitro into the
      beta-oligomer. We propose a possible mechanism for the formation of the beta
      oligomer, triggered by intermolecular contacts between constantly rearranging
      structures. It is concluded that the beta-oligomer is not preceded by precursors
      with beta-sheet structure but by a partially unfolded clearly distinguishable
      alpha-helical state.

PMID- 17210576
TI  - Phosphatase type 2A-dependent and -independent pathways for ATR phosphorylation
      of Chk1.
AB  - ATM and Rad3-related (ATR) is a regulatory kinase that, when activated by
      hydroxyurea, UV, or human immunodeficiency virus-1 Vpr, causes cell cycle arrest
      through Chk1-Ser(345) phosphorylation. We demonstrate here that of these three
      agents only Vpr requires protein phosphatase type 2A (PP2A) to activate ATR for
      Chk1-Ser(345) phosphorylation. A requirement for PP2A by Vpr was first shown with
      the PP2A-specific inhibitor okadaic acid, which reduced Vpr-induced G(2) arrest
      and Cdk1-Tyr(15) phosphorylation. Using small interference RNA to down-regulate
      specific subunits of PP2A indicated that the catalytic beta-isoform PP2A(Cbeta)
      and the A regulatory alpha-isoform PP2A(Aalpha) are involved in the G(2)
      induction, and these downregulations decreased the Vpr-induced, ATR-dependent
      phosphorylations of Cdk1-Tyr(15) and Chk1-Ser(345). In contrast, the same down
      regulations had no effect on hydroxyurea- or UV-activated ATR-dependent Chk1
      Ser(345) phosphorylation. Vpr and hydroxyurea/UV all induce ATR-mediated
      gammaH2AX-Ser(139) phosphorylation and foci formation, but down-regulation of
      PP2A(Aalpha) or PP2A(Cbeta) did not decrease gammaH2AX-Ser(139) phosphorylation
      by any of these agents or foci formation by Vpr. Conversely, H2AX down-regulation
      had little effect on PP2A(Aalpha/Cbeta)-mediated G(2) arrest and Chk1-Ser(345)
      phosphorylation by Vpr. The expression of vpr increases the amount and
      phosphorylation of Claspin, an activator of Chk1 phosphorylation. Down-regulation
      of either PP2A(Cbeta) or PP2A(Aalpha) had little effect on Claspin
      phosphorylation, but the amount of Claspin was reduced. Claspin may then be one
      of the phosphoproteins through which PP2A(Aalpha/Cbeta) affects Chk1
      phosphorylation when ATR is activated by human immunodeficiency virus-1 Vpr.

PMID- 17210577
TI  - Maize beta-glucosidase-aggregating factor is a polyspecific jacalin-related
      chimeric lectin, and its lectin domain is responsible for beta-glucosidase
      aggregation.
AB  - In certain maize genotypes, called "null," beta-glucosidase does not enter gels
      and therefore cannot be detected on zymograms after electrophoresis. Such
      genotypes were originally thought to be homozygous for a null allele at the glu1
      gene and thus devoid of enzyme. We have shown that a beta-glucosidase-aggregating
      factor (BGAF) is responsible for the "null" phenotype. BGAF is a chimeric protein
      consisting of two distinct domains: the disease response or "dirigent" domain and
      the jacalin-related lectin (JRL) domain. First, it was not known whether the
      lectin domain in BGAF is functional. Second, it was not known which of the two
      BGAF domains is involved in beta-glucosidase binding and aggregation. To this
      end, we purified BGAF to homogeneity from a maize null inbred line called H95.
      The purified protein gave a single band on SDS-PAGE, and the native protein was a
      homodimer of 32-kDa monomers. Native and recombinant BGAF (produced in
      Escherichia coli) agglutinated rabbit erythrocytes, and various carbohydrates and
      glycoproteins inhibited their hemagglutination activity. Sugars did not have any
      effect on the binding of BGAF to the beta-glucosidase isozyme 1 (Glu1), and the
      BGAF-Glu1 complex could still bind lactosyl-agarose, indicating that the sugar
      binding site of BGAF is distinct from the beta-glucosidase-binding site. Neither
      the dirigent nor the JRL domains alone (produced separately in E. coli) produced
      aggregates of Glu1 based on results from pull-down assays. However, gel shift and
      competitive binding assays indicated that the JRL domain binds beta-glucosidase
      without causing it to aggregate. These results with those from deletion
      mutagenesis and replacement of the JRL domain of a BGAF homolog from sorghum,
      which does not bind Glu1, with that from maize allowed us to conclude that the
      JRL domain of BGAF is responsible for its lectin and beta-glucosidase binding and
      aggregating activities.

PMID- 17210578
TI  - Regulatory mechanisms differ in UMP kinases from gram-negative and gram-positive
      bacteria.
AB  - In this work, we examined the regulation by GTP and UTP of the UMP kinases from
      eight bacterial species. The enzyme from Gram-positive organisms exhibited
      cooperative kinetics with ATP as substrate. GTP decreased this cooperativity and
      increased the affinity for ATP. UTP had the opposite effect, as it decreased the
      enzyme affinity for ATP. The nucleotide analogs 5-bromo-UTP and 5-iodo-UTP were 5
      10 times stronger inhibitors than the parent compound. On the other hand, UMP
      kinases from the Gram-negative organisms did not show cooperativity in substrate
      binding and catalysis. Activation by GTP resulted mainly from the reversal of
      inhibition caused by excess UMP, and inhibition by UTP was accompanied by a
      strong increase in the apparent K(m) for UMP. Altogether, these results indicate
      that, depending on the bacteria considered, GTP and UTP interact with different
      enzyme recognition sites. In Gram-positive bacteria, GTP and UTP bind to a single
      site or largely overlapping sites, shifting the T R equilibrium to either the R
      or T form, a scenario corresponding to almost all regulatory proteins, commonly
      called K systems. In Gram-negative organisms, the GTP-binding site corresponds to
      the unique allosteric site of the Gram-positive bacteria. In contrast, UTP
      interacts cooperatively with a site that overlaps the catalytic center, i.e. the
      UMP-binding site and part of the ATP-binding site. These characteristics make UTP
      an original regulator of UMP kinases from Gram-negative organisms, beyond the
      common scheme of allosteric control.

PMID- 17210579
TI  - Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated
      protein kinase kinase kinase in a heteromeric complex with ASK1.
AB  - Apoptosis signal-regulating kinase (ASK) 1 is a mitogen-activated protein kinase
      kinase kinase (MAP3K) in the c-Jun N-terminal kinase (JNK) and p38 mitogen
      activated protein kinase pathways that play multiple important roles in cytokine
      and stress responses. Here we show that ASK2, a highly related serine/threonine
      kinase to ASK1, also functions as a MAP3K only in a heteromeric complex with
      ASK1. We found that endogenous ASK2 was constitutively degraded in ASK1-deficient
      cells, suggesting that ASK1 is required for the stability of ASK2. ASK2 in a
      heteromeric complex with a kinase-negative mutant of ASK1 (ASK1-KN) effectively
      activated MAP2K and was more competent to respond to oxidative stress than ASK2
      alone. Knockdown of ASK2 revealed that ASK2 was required for oxidative stress
      induced JNK activation. These results suggest that ASK2 forms a functional MAP3K
      complex with ASK1, in which ASK1 supports the stability and the active
      configuration of ASK2. Moreover, ASK2 was found to activate ASK1 by direct
      phosphorylation, suggesting that ASK1 and ASK2 in a heteromeric complex
      facilitate their activities to each other by distinct mechanisms. Such a
      formation of functional heteromeric complex between different MAP3Ks may be
      advantageous for cells to cope with a wide variety of stimuli by fine regulation
      of cellular responses.

PMID- 17210580
TI  - Synergistic potent insulin release by combinations of weak secretagogues in
      pancreatic islets and INS-1 cells.
AB  - Insulin secretion by the beta cell depends on anaplerosis in which insulin
      secretagogues are metabolized by mitochondria into molecules that are most likely
      exported to the extramitochondrial space where they have signaling roles.
      However, very little is known about the products of anaplerosis. We discovered an
      experimental paradigm that has begun to provide new information about these
      products. When various intracellular metabolites were applied in combination to
      overnight-cultured rat or human pancreatic islets or to INS-1 832/13 cells, they
      interacted synergistically to strongly stimulate insulin release. When these same
      metabolites were applied individually to these cells, insulin stimulation was
      poor. Discerning the contributions of the individual compounds to metabolism has
      begun to allow us to dissect some of the pathways involved in insulin secretion,
      which was not possible from studying individual secretagogues. Monomethyl
      succinate (MMS) combined with a barely stimulatory concentration of alpha
      ketoisocaproate (KIC) (2 mm) stimulated insulin release in cultured rat islets 18
      fold (versus 21-fold for 16.7 mm glucose). MMS plus low glucose (2 mm) or
      pyruvate (5 mm) gave 11- and 9-fold stimulations. These agents also potentiated
      MMS-induced insulin release in fresh islets, and KIC plus MMS gave synergistic
      insulin release in cultured human islets. In INS-1 cells, neither MMS nor KIC (10
      mm) was an insulin secretagogue, but when added together KIC (2 mm) and MMS
      stimulated insulin release 7-fold (versus 12-fold for glucose). In islets and INS
      1 cells, conditions that stimulated insulin release caused large relative
      increases in acetoacetate, which is a precursor of pathways to short chain acyl
      CoAs. Liquid chromatography-tandem mass spectrometry measurements of acetyl-CoA,
      acetoacetyl-CoA, succinyl-CoA, hydroxymethylglutaryl-CoA, and malonyl-CoA
      confirmed that they were increased by insulin secretagogues. The results suggest
      a new mechanism of insulin secretion in which anaplerosis increases short chain
      acyl-CoAs that have roles in insulin exocytosis.

PMID- 17210581
TI  - Benefit Finding Scale for Children: preliminary findings from a childhood cancer
      population.
AB  - OBJECTIVE: To describe the development of a brief measure of benefit finding for
      children. Data regarding the psychometrics and validity of the instrument were
      examined in a sample of children with cancer. METHODS: A cross-sectional sample
      of children with cancer (N = 199, ages 7-18 years) completed the Benefit Finding
      Scale for Children (BFSC) along with measures of adaptive style,
      optimism/pessimism, post-traumatic stress symptoms, and health-related quality of
      life. RESULTS: The BFSC was found to be a unidimensional measure with excellent
      internal reliability. Benefit finding was not related to age or gender, but
      differed as a function of race/ethnicity. No differences were found by diagnostic
      category, but a significant relationship was found with age at diagnosis and time
      elapsed since diagnosis. Small, but significant positive correlations were found
      with measures of optimism and self-esteem, and a negative correlation with
      anxiety. No relation was found between benefit finding and post-traumatic stress
      symtpoms or other domains of health-related quality of life. CONCLUSION: The BFSC
      shows promise as a measure of benefit finding in children. The measure could be
      readily adapted for other populations of children experiencing trauma.

PMID- 17210582
TI  - Adolescents with renal disease in an adult world: meeting the challenge of
      transition of care.

PMID- 17210583
TI  - Soluble endoglin is an accurate predictor and a pathogenic molecule in pre
      eclampsia.

PMID- 17210584
TI  - Community-based screening for chronic kidney disease among populations older than
      40 years in Beijing.
AB  - BACKGROUND: Chronic kidney disease (CKD) is a public health problem, while data
      from developing countries are limited. We sought to investigate the
      epidemiological features of kidney damage in metropolis-residing Chinese adults
      (>40 years old), and to determine the associated factors of CKD. METHODS: Two
      thousand three hundred and fifty-three residents in one district of Beijing were
      interviewed and tested for albuminuria, reduced renal function, haematuria and
      pyuria. The associations between demographic characteristics, health
      characteristics and indicators of kidney damage were examined. RESULTS:
      Albuminuria was detected in 6.2% of subjects; reduced renal function was found in
      5.2% of subjects; haematuria was found in 0.8% and non-infective pyuria was found
      in 0.09%. Approximately, 11.3% (95% confidence interval: 10.0-12.8%) of subjects
      had at least one indicator of kidney damage. The awareness rate of CKD was only
      7.2%. Systolic blood pressure and diabetes were independently associated with
      albuminuria. Age, diastolic blood pressure, hypercholesteraemia,
      hypertriglyceridaemia and hyperuricaemia were independently associated with
      reduced renal function. CONCLUSIONS: This is the first report on the prevalence
      of CKD in a community-based population within a developing country, determined
      using protocols recommended by kidney disease improving global outcomes (KDIGO).
      The prevalence of CKD in our population was close to the levels observed in
      developed countries, and the spectrum of CKD and associated factors were similar
      to developed countries. Results from this study suggest that strategies aimed at
      an intervention of hypertension and other metabolic disorders might prove
      effective in controlling the pandemic of CKD in China, as well as other
      developing countries.

PMID- 17210585
TI  - Salt-sensitive hypertension--update on novel findings.

PMID- 17210586
TI  - Pharmacoeconomics in nephrology: considerations on cost-effectiveness of
      screening for albuminuria.

PMID- 17210587
TI  - Sequential development of pulmonary renal syndrome associated with c-ANCA 3 years
      after development of anti-GBM glomerulonephritis.

PMID- 17210588
TI  - Caspofungin in kidney transplant recipients with refractory invasive candidiasis.

PMID- 17210589
TI  - Association of cystatin C and estimated GFR with inflammatory biomarkers: the
      Heart and Soul Study.
AB  - BACKGROUND: Cystatin C is a marker of kidney function that may also be associated
      with inflammation. In this study, we compared the relative strengths of
      association of cystatin C and estimated glomerular filtration rate (eGFR) with
      inflammatory biomarkers. METHODS: We measured serum cystatin C and creatinine in
      990 outpatients with coronary artery disease enrolled in the Heart and Soul
      Study. GFR was estimated (eGFR) by the abbreviated Modification of Diet in Renal
      Disease (MDRD) equation. We compared the associations of serum cystatin C and
      eGFR with C-reactive protein (CRP) and fibrinogen, after adjustment for 24 h
      creatinine clearance. RESULTS: Cystatin C concentrations had moderate
      correlations with CRP (r=0.15, P<0.001) and fibrinogen (r=0.26, P<0.0001); eGFR
      had similar correlations with CRP (r=-0.17, P=0.01) and fibrinogen (r=-0.25,
      P<0.001) among persons with eGFR<or=60 ml/min, but had no association with either
      biomarker among those with eGFR>60 ml/min (r=0.04, P=0.32; r=-0.03, P=0.38).
      Quartiles of cystatin C were strongly and directly associated with CRP (P=0.02)
      and fibrinogen (P<0.007) after multivariate adjustment. However, these
      associations disappeared after adjustment for creatinine clearance (P=0.26 and
      0.23, respectively). CONCLUSIONS: Cystatin C concentrations have moderate
      associations with CRP and fibrinogen that are not independent of creatinine
      clearance. Although a gold standard of kidney function is lacking, this analysis
      suggests that cystatin C captures an association of mildly impaired kidney
      function with increased inflammation.

PMID- 17210590
TI  - Epoetin trials: randomised controlled trials don't always mimic observational
      data.

PMID- 17210591
TI  - Medical treatment options in patients with metastatic renal cell carcinoma.

PMID- 17210592
TI  - Specific humoral rejection of a pancreas allograft in a recipient of pancreas
      after kidney transplantation.

PMID- 17210593
TI  - Prevalence and predictors of epoetin hyporesponsiveness in chronic kidney disease
      patients.
AB  - BACKGROUND: The required erythropoiesis-stimulating agent (ESA) dose varies when
      correcting anaemia in chronic kidney disease (CKD) patients. This analysis was
      performed to identify the prevalence of and factors associated with ESA
      hyporesponsiveness. METHODS: This analysis was a post hoc evaluation of epoetin
      alfa dosage requirements in a subgroup of patients from the Effect of early
      Correction of Anemia on the Progression of CKD study. The patients in this
      subgroup were randomly assigned to the high haemoglobin target group (14-15 g/dl
      for men and 13-14 g/dl for women) and completed a 4-month haemoglobin
      stabilization phase with complete epoetin dosage data. The relationship of
      demographics, disease characteristics and laboratory measures with epoetin dosage
      were evaluated using Pearson's correlation, association measures and analysis of
      covariance (ANCOVA) models. RESULTS: Of the 93 patients evaluated in this
      subgroup analysis, 14 (15%) were hyporesponsive to epoetin (maximum dosage >100
      IU/kg/week during stabilization). An ANCOVA analysis showed that 52% of the
      observed variability in epoetin dosage at completion of the stabilization phase
      could be accounted for by diabetes as the primary cause of kidney disease,
      angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB)
      use, proteinuria, transferrin saturation, age, pre-treatment haemoglobin,
      geographical region, serum iron and body mass index (BMI). Unidentified patient
      characteristics accounted for an additional 16% of the dosage variance.
      CONCLUSIONS: Older age, higher BMI, anaemia, ACE inhibitor/ARB use and diabetes
      as the primary cause of kidney disease are associated with increased epoetin
      requirements when normalizing haemoglobin in anaemic CKD patients.

PMID- 17210594
TI  - Renal tubular acidosis after kidney transplantation--incidence, risk factors and
      clinical implications.
AB  - BACKGROUND: Renal tubular acidosis (RTA) is a non-anion gap metabolic acidosis
      and is generally mild and asymptomatic in kidney recipients. Although calcineurin
      inhibitors, suboptimal allograft function, donor age and acute rejection have
      been associated with RTA, no detailed study has been conducted to investigate the
      prevalence and clinical implications of RTA in long-term kidney recipients.
      METHODS: In this cross-sectional study, we enrolled 109 patients (74 males, 35
      females) for the study [patients with glomerular filtration rate (GFR) <30
      ml/min/1.73 m(2), unstable allograft function, diarrhoea, and respiratory disease
      were excluded]. Thirty-six patients (33%) were found to have RTA on the basis of
      plasma bicarbonate, arterial pH, urine and serum anion gap measurements. RESULTS:
      Deceased donor transplantation [P = 0.034, 95% confidence interval (CI): 1.10
      13.27], female gender (P = 0.017, 95% CI: 1.23-8.50), and lower GFR (55.8 +/-
      19.4 in RTA and 66.1 +/- 15.9 ml/min/1.73 m(2) in non-RTA, P = 0.002, 95% CI:
      1.10-13.27) were independent risk factors for RTA. Also, C-reactive protein was
      found to be higher in the RTA group (2.7 +/- 1.5 vs 2.0 +/- 1.5 mg/dl, P = 0.03),
      while no difference was noticed in body mass index or serum albumin. Analysis of
      the prevalence of osteoporosis and osteopenia in patients with RTA and without
      RTA, respectively, revealed no difference in frequency of osteoporosis (33% vs
      31%) or osteopenia (33% vs 47%). CONCLUSION: Although long-term kidney recipients
      have a relatively high prevalence of RTA, it is usually mild and subclinical.
      Further studies are needed to clarify long-term effects of RTA in kidney
      recipients.

PMID- 17210595
TI  - Minimal-change nephropathy and chronic hepatitis C infection: coincidental or
      associated?

PMID- 17210596
TI  - Urinary pH affects albumin concentrations after prolonged frozen storage.

PMID- 17210598
TI  - Genomic species identification is important to delineate the pathological
      characteristics of Acinetobacter in tunnelled, cuffed haemodialysis catheter
      related bacteraemia.

PMID- 17210597
TI  - Acute renal failure and febrile rash--infectious or not? Adult Kawasaki disease
      (KD).

PMID- 17210599
TI  - Atherosclerotic renovascular disease: beyond the renal artery stenosis.

PMID- 17210600
TI  - Renal vessel reconstruction in kidney transplantation using a
      polytetrafluoroethylene (PTFE) vascular graft.
AB  - BACKGROUND: We report a rare experience in reconstructing short renal vessels in
      kidney transplantation using polytetrafluroethylene (PTFE) vascular grafts.
      METHODS: The short renal vessels in three kidney grafts were managed by the
      interposition of PTFE vascular grafts. Two grafts were from deceased donors and
      the third was a renal auto-transplant graft. RESULTS: PTFE grafts were used to
      lengthen short renal veins in two kidney grafts and a short renal artery in one.
      The warm ischaemia time was under 1 h and all kidneys functioned well post
      operatively. Excellent blood perfusion in the three renal grafts was present on
      postoperative MAG 3 renal scan. No intra-operative or post-operative
      complications were encountered. CONCLUSIONS: In the three described patients, the
      use of PTFE vascular graft presented no additional morbidity to the kidney
      transplant operation and no post-oerative complication was related to its use.
      However, more data are necessary to conclude that PTFE graft can be used safely
      in kidney transplantation.

PMID- 17210601
TI  - Nephrologist extraordinary--Michael Darmady (1906-1989).
AB  - Michael Darmady (1906-1989) is now largely forgotten, although he played a major
      role in several areas of Nephrology in the early days of the speciality, both as
      a clinician and as a pathologist. His contributions to the early understanding of
      acute renal failure and of the use of haemodialysis during the 1940s have been
      particularly neglected. His nephron microdissection work achieved some influence
      around 1960, but today he is remembered principally for his classical work on the
      morphology of the ageing kidney, and on being the first to point out the poorer
      outlook of kidneys transplanted from older donors, in 1974.

PMID- 17210602
TI  - Necrotizing crescentic glomerulonephritis--a conditional knockout model discloses
      new therapeutic challenges.

PMID- 17210603
TI  - An unusual presentation of renal cell carcinoma with late metastases to the small
      intestine, thyroid gland, nose and skull base.

PMID- 17210605
TI  - Solar ultraviolet-B radiation and insect herbivory trigger partially overlapping
      phenolic responses in Nicotiana attenuata and Nicotiana longiflora.
AB  - BACKGROUND AND AIMS: Plants exposed to solar ultraviolet-B radiation (UV-B, 280
      315 nm) frequently suffer less insect herbivory than do plants that receive
      attenuated levels of UV-B. This anti-herbivore effect of solar UV-B exposure,
      which has been documented in several ecosystems, is in part mediated by changes
      in plant tissue quality. Exposure to UV-B can modify the abundance of a number of
      secondary metabolites, including phenolic compounds with potential impacts on
      insect herbivores. The aim of this study is to assess the potential anti
      herbivore role of UV-B-induced phenolic compounds by comparing the phenolic
      profiles induced by UV-B and simulated insect herbivory in two wild species of
      the genus Nicotiana. METHODS: Plants grown under field and glasshouse conditions
      were exposed to contrasting levels of UV-B. Half of the plants of the attenuated
      UV-B treatment were given a simulated herbivory treatment, where leaves were
      mechanically damaged and immediately treated with oral secretions of Manduca
      sexta caterpillars. This treatment is known to mimic the impact of real herbivory
      on the expression of plant defences in Nicotiana. Phenolic profiles induced by UV
      B and simulated herbivory were characterized using high-performance liquid
      chromatography-mass spectrometry (HPLC-MS). KEY RESULTS: UV-B induced the
      accumulation of several UV-absorbing phenolic compounds that are known to play a
      significant role in UV-B screening. Interestingly, there was a significant
      convergence in the phenolic profiles induced by UV-B and simulated herbivory:
      chlorogenic acid and dicaffeoylspermidine isomers, in particular, displayed a
      similar pattern of response to these stimuli. In contrast, rutin, the only
      flavonoid that accumulated in significant quantities in the experiments, was only
      induced by UV-B. CONCLUSIONS: The results suggest that the anti-herbivory effect
      induced by UV-B may be mediated at least in part by the accumulation of
      phenylpropanoid derivatives that are similar to those induced by the plant in
      response to insect herbivory.

PMID- 17210606
TI  - Biomass allocation is an important determinant of the tannin concentration in
      growing plants.
AB  - BACKGROUND AND AIMS: Condensed tannins (CTs) in the diet affect consumers in a
      concentration-dependent manner. Because of their importance in plant defence
      against herbivores and pathogens as well as their potential application against
      gastrointestinal parasites of ruminants in agronomy, an understanding of the
      seasonal dynamics of CT concentrations during plant growth is essential. METHODS:
      Over a vegetation period, CT concentrations in leaves, stems and roots and the
      biomass proportions between these organs were investigated in Onobrychis
      viciifolia, Lotus corniculatus and Cichorium intybus. Based on the experimental
      data, a model has been suggested to predict CT concentrations in harvestable
      biomass of these species. KEY RESULTS: During the experiment, leaf mass fractions
      of plants decreased from 85, 64, 85 to 30, 18, 39 % d. wt in Onobrychis, Lotus
      and Cichorium, respectively, and proportions of stems and roots increased
      accordingly. While CT concentrations almost doubled in leaves in Onobrychis (from
      52 to 86 mg g(-1) d. wt, P<0.001) and Lotus (from 25 to 54 mg g(-1) d. wt,
      P<0.001), they were stable at low levels in expanding leaves of Cichorium (5 mg
      g(-1) d. wt) and in stems and roots of all investigated species. Due to an
      inverse effect of the increasing CT concentrations in leaves and simultaneous
      dilution from increasing proportions of 'CT-poor' stems, CT concentrations in
      harvestable biomass were stable over time in all investigated species: 62, 26 and
      5 mg g(-1) d. wt for Onobrychis, Lotus and Cichorium, respectively. CONCLUSIONS:
      As a consequence of the unequal distribution of tannins in different plant parts
      and due to the changing biomass proportions between them, various herbivores
      (e.g. a leaf-eating insect and a grazing ruminant) may find not only different
      concentrations of CT in their diets but also different CT dynamics during the
      season. For the prediction of seasonal variations of CT concentrations, biomass
      allocation and accumulation of none-CT plant material are likely to be as
      important predictors as the knowledge of CT synthesis and its regulation.

PMID- 17210607
TI  - Above-ground biomass investments and light interception of tropical forest trees
      and lianas early in succession.
AB  - BACKGROUND AND AIMS: Crown structure and above-ground biomass investment was
      studied in relation to light interception of trees and lianas growing in a 6
      month-old regenerating forest. METHODS: The vertical distribution of total above
      ground biomass, height, diameter, stem density, leaf angles and crown depth were
      measured for individual plants of three short-lived pioneers (SLPs), four long
      lived pioneers (LLPs) and three lianas. Daily light interception per individual
      Phi(d) was calculated with a canopy model. The model was then used to estimate
      light interception per unit of leaf mass (Phi(leaf mass)), total above-ground
      mass (Phi(mass)) and crown structure efficiency (E(a), the ratio of absorbed vs.
      available light). KEY RESULTS: The SLPs Trema and Ochroma intercepted higher
      amounts of light per unit leaf mass (Phi(leaf mass)) because they had shallower
      crowns, resulting in higher crown use efficiency (E(a)) than the other species.
      These SLPs (but not Cecropia) were also taller and intercepted more light per
      unit leaf area (Phi(area)). LLPs and lianas had considerably higher amounts of
      leaf mass and area per unit above-ground mass (LMR and LAR, respectively) and
      thus attained Phi(mass) values similar to the SLPs (Phi(mass)=Phi(area)xLAR).
      Lianas, which were mostly self-supporting, had light interception efficiencies
      similar to those of the trees. CONCLUSIONS: These results show how, due to the
      trade-off between crown structure and biomass allocation, SLPs, and LLPs and
      lianas intercept similar amount of light per unit mass which may contribute to
      the ability of the latter two groups to persist.

PMID- 17210608
TI  - A novel method of supplying nutrients permits predictable shoot growth and root :
      shoot ratios of pre-transplant bedding plants.
AB  - BACKGROUND AND AIMS: Growth of bedding plants, in small peat plugs, relies on
      nutrients in the irrigation solution. The object of the study was to find a way
      of modifying the nutrient supply so that good-quality seedlings can be grown
      rapidly and yet have the high root : shoot ratios essential for efficient
      transplanting. METHODS: A new procedure was devised in which the concentrations
      of nutrients in the irrigation solution were modified during growth according to
      changing plant demand, instead of maintaining the same concentrations throughout
      growth. The new procedure depends on published algorithms for the dependence of
      growth rate and optimal plant nutrient concentrations on shoot dry weight W(s) (g
      m(-2)), and on measuring evapotranspiration rates and shoot dry weights at weekly
      intervals. Pansy, Viola tricola 'Universal plus yellow' and petunia, Petunia
      hybrida 'Multiflora light salmon vein' were grown in four independent experiments
      with the expected optimum nutrient concentration and fractions of the optimum.
      Root and shoot weights were measured during growth. KEY RESULTS: For each level
      of nutrient supply W(s) increased with time (t) in days, according to the
      equation DeltaW(s)/Deltat=K(2)W(s)/(100+W(s)) in which the growth rate
      coefficient (K(2)) remained approximately constant throughout growth. The value
      of K(2) for the optimum treatment was defined by incoming radiation and
      temperature. The value of K(2) for each sub-optimum treatment relative to that
      for the optimum treatment was logarithmically related to the sub-optimal nutrient
      supply. Provided the aerial environment was optimal, R(sb)/R(o) approximately
      W(o)/W(sb) where R is the root : shoot ratio, W is the shoot dry weight, and sb
      and o indicate sub-optimum and optimum nutrient supplies, respectively. Sub
      optimal nutrient concentrations also depressed shoot growth without appreciably
      affecting root growth when the aerial environment was non-limiting. CONCLUSION:
      The new procedure can predict the effects of nutrient supply, incoming radiation
      and temperature on the time course of shoot growth and the root : shoot ratio for
      a range of growing conditions.

PMID- 17210609
TI  - Hybridization and sexual reproduction in the invasive alien Fallopia
      (Polygonaceae) complex in Belgium.
AB  - BACKGROUND AND AIMS: The knotweed complex, Fallopia spp. (Polygonaceae), belongs
      to the most troublesome invasive species in Europe and North America. Vegetative
      regeneration is widely recognized as the main mode of reproduction in the
      adventive regions. However, the contribution of sexual reproduction to the
      success of these invasive species has only been detailed for the British Isles.
      An examination was made as to how hybridization may influence the sexual
      reproduction of the complex in Belgium and to determine how it may contribute to
      the dispersal of the species. METHODS: Studies were made of floral biology,
      reproductive success, seed rain, seed bank, germination capacity, seedling
      survival and dispersal capacity in order to characterize the reproductive biology
      of the species. Moreover, chromosome counts and flow cytometry were used to
      assess the hybrid status of seedlings produced by sexual reproduction. KEY
      RESULTS: In the area investigated, extensive sexual reproduction by hybridization
      within the complex, including one horticultural species, was demonstrated. A
      small percentage of seeds may be dispersed outside the maternal clone (>16 m)
      allowing the formation of genetically differentiated individuals. Seed
      germination was possible even after a winter cold period. CONCLUSIONS: The
      extensive sexual reproduction by hybridization could further contribute to the
      dramatic invasive success of knotweeds in Belgium and should not be
      underestimated when considering control and management measures.

PMID- 17210611
TI  - Tobacco smoking and gastric cancer risk: an evaluation based on a systematic
      review of epidemiologic evidence among the Japanese population.
AB  - BACKGROUND: We evaluated the association between tobacco smoking and gastric
      cancer risk among the Japanese population based on a systematic review of
      epidemiologic evidence. METHODS: Original data were collected by searches of
      MEDLINE using PubMed, complemented with manual searches. Evaluation of
      associations was based on the strength of evidence and the magnitude of
      association, together with biological plausibility, as evaluated previously by
      the International Agency for Research on Cancer. RESULTS: Ten cohort studies and
      16 case-control studies were identified. In men, most studies reported moderate
      or strong positive associations between smoking and gastric cancer. In women, the
      positive association was weaker than in men. Of eight studies (three cohort
      studies and five case-case control studies), two cohort and three case control
      studies reported a weakly to strongly increased risk of gastric cancer. The
      summary relative risk for current smokers was estimated to be 1.56 (95%
      confidence intervals 1.36-1.80), 1.79 (1.51-2.12), 1.22 (1.07-1.38) for the total
      population, men and women, respectively. CONCLUSION: We conclude that there is
      convincing evidence that tobacco smoking moderately increases the risk of gastric
      cancer among the Japanese population.

PMID- 17210612
TI  - A case of primary unknown carcinoma with lymphatic spread.

PMID- 17210613
TI  - International comparisons of cumulative risk of pancreatic cancer, from cancer
      incidence in five continents Vol. VIII.

PMID- 17210615
TI  - Bottle feeding and exposure to Toxocara as risk factors for wheezing illness
      among under-five Amazonian children: a population-based cross-sectional study.
AB  - We investigated the prevalence and risk factors for wheezing and asthma in young
      Amazonian children. A population-based cross-sectional survey of 606 children
      aged 6-59 months was performed in two small towns in Acre State, Northwestern
      Brazil. Information on outcome variables (recent wheezing and medical diagnosis
      of asthma) and demographic, socioeconomic, environmental, maternal and
      nutritional variables was obtained by interviewing children's mothers or
      guardians. Infections with intestinal parasites and antibodies to the zoonotic
      nematode Toxocara were diagnosed using standard laboratory techniques. Multiple
      unconditional logistic regression models were used to describe associations
      between independent variables and outcomes. The prevalence of recent wheezing
      (one or more reported episodes in the past 12 months) was 42.6%, but only 19.8%
      of wheezing children were also reported to have a medical diagnosis of asthma
      (prevalence, 8.5%); 21.5% of the children examined had antibodies to Toxocara.
      Increased risk of asthma was independently associated with early introduction of
      bottle feeding, defined as <4 months of exclusive breastfeeding [adjusted odds
      ratio (aOR) = 2.21, 95% confidence interval (95% CI), 1.07-4.59, P = 0.033], and
      seropositivity to Toxocara (aOR = 2.37, 95% CI 1.17-4.77, P = 0.016), suggesting
      two potential targets for public health interventions.

PMID- 17210616
TI  - Lipoteichoic acid and muramyl dipeptide synergistically induce maturation of
      human dendritic cells and concurrent expression of proinflammatory cytokines.
AB  - Maturation is an important process by which dendritic cells (DC) develop the
      potent antigen-presentation capacity necessary for efficient activation of
      adaptive immunity. Here, we have investigated the ability of lipoteichoic acid
      (LTA) and muramyl dipeptide (MDP; the minimal structural unit of peptidoglycan
      with immunostimulating activity) to induce maturation of human immature DC (iDC),
      derived from peripheral blood CD14-positive cells, and the production of
      proinflammatory cytokines. Exposure of iDC to staphylococcal LTA (StLTA) at 1 or
      10 microg/ml or MDP at 0.1 or 1 microg/ml alone had little effect on the
      expression of CD80 and CD83, with a minor increase in expression of CD86, all of
      which are indicative of cell surface markers for maturation. However, there was a
      synergistic expression of these molecules when iDC were stimulated with StLTA and
      MDP together. It is interesting that selective induction of MHC Class II
      expression was observed during the DC maturation, only when costimulated with LTA
      plus MDP, and Escherichia coli LPS induced dramatic expression of MHC Classes I
      and II. Endocytosis assay using Dextran-FITC showed that costimulation with StLTA
      and MDP attenuated the endocytic capacity of the DC, which is a typical
      phenomenon of DC maturation. Concomitantly, increased expression of DEC-205, but
      decreased expression of CD206, was observed under the same costimulating
      condition. Furthermore, ELISA showed that secretions of TNF-alpha and IL-12 p40,
      but not IL-10, were induced in iDC by the costimulation. These results suggest
      that StLTA and MDP synergistically induce maturation and activation of human DC.

PMID- 17210617
TI  - Analysis of the thiol status of peripheral blood leukocytes in rheumatoid
      arthritis patients.
AB  - Although the exact etiology of rheumatoid arthritis (RA) remains unknown, there
      is increasing evidence that reactive oxygen species and a pro-oxidant/antioxidant
      imbalance are an important part of the pathogenesis of joint tissue injury. Flow
      cytometry was used to evaluate the thiol status [surface-thiols and intracellular
      glutathione (iGSH)] of leukocytes from RA patients and controls. Levels of
      surface-thiols and iGSH of leukocytes from RA patients were significantly lower
      than of leukocytes from controls. CD53, a glycoprotein of the tetraspanin
      superfamily, which coprecipitates with the GSH recycling enzyme gamma-glutamyl
      transpeptidase, was elevated significantly on leukocytes from RA patients
      compared with leukocytes from controls. Surface-thiols and GSH play important
      roles in redox buffering of cells, providing protection from oxidative stress.
      The chronic inflammation of RA has been associated with oxidative stress, which
      is shown to cause a decline in the levels of cellular antioxidant sulfhydryls (R
      SH). As antioxidant-protective levels also decline with age, the problem is
      compounded in older RA patients, who did have fewer R-SH. Chronic stress can also
      have an effect on telomere lengths, determining cell senescence and longevity.
      Although telomeres shorten with increasing age, our flow cytometry studies
      indicate that accelerated shortening in telomere lengths occurs with increasing
      age of RA patients, suggesting premature cellular aging. The paradox is that
      lymphocytes from RA patients are believed to resist apoptosis, and we suggest
      that the elevated expression of CD53, which results from the increased oxidative
      stress, may protect against apoptosis.

PMID- 17210618
TI  - The cation-independent mannose 6-phosphate receptor is involved in lysosomal
      delivery of serglycin.
AB  - To clarify the sorting mechanism of the lysosomal/granular proteoglycan
      serglycin, we treated human promonocytic U937 cells with p-nitrophenyl-beta-D
      xyloside (PNP-xyl) and cycloheximide. In the absence of protein synthesis, the
      carbohydrate moiety of serglycin was synthesized as PNP-xyl-chondroitin sulfate
      (CS), and most of it was delivered to lysosomes and degraded. Further, an
      augmented lysosomal targeting of serglycin in the presence of tunicamycin
      suggested that a sorting/lectin receptor with multiple specificity was involved
      with an increased capacity for serglycin in the absence of N-glycosylation.
      Correspondingly, the cation-independent mannose 6-phosphate receptor (CI-MPR) and
      sortilin were observed to bind to immobilized CS. These receptors were eluted in
      the presence of 200-400 mM and 100-250 mM NaCl, respectively. After treating the
      cells with a cross-linking reagent, a portion of the sulfated proteoglycan was
      coimmunoprecipitated with the CI-MPR but not with sortilin. In the presence of
      phorbol ester, lysosomal targeting of serglycin and to a lesser extent, of
      cathepsin D was inhibited. We conclude that the CI-MPR participates in lysosomal
      and granular targeting of serglycin and basic proteins such as lysozyme
      associated with the proteoglycan in hematopoietic cells.

PMID- 17210619
TI  - Splanchnic ischemia and reperfusion injury is reduced by genetic or
      pharmacological inhibition of TNF-alpha.
AB  - In the present study, we used TNF-alpha receptor 1 knockout (TNF-alphaR1KO) mice
      to evaluate a possible role of TNF-alpha on the pathogenesis of ischemia and
      reperfusion injury of the multivisceral organs. Ischemia and reperfusion injury
      was induced in mice by clamping the superior mesenteric artery and the celiac
      artery for 30 min, followed thereafter by reperfusion. Sixty minutes after
      reperfusion, animals were killed for histological examination and biochemical
      studies. Injured wild-type (WT) mice developed a significant increase of ileum
      TNF-alpha levels, myeloperoxidase activity, and marked histological injury and
      apoptosis. Ischemia and reperfusion injury of the multivisceral organs was also
      associated with a significant mortality. Reperfused ileum sections from injured
      WT mice showed positive staining for P-selectin, VCAM, ICAM-1, and E-selectin.
      The intensity and degree of P-selectin, E-selectin, VCAM, and ICAM-1 were reduced
      markedly in tissue sections from injured TNF-alphaR1KO mice. Ischemia and
      reperfusion-injured TNF-alphaR1KO mice also showed a significant reduction of
      neutrophil infiltration into the intestine, a reduction of apoptosis, an improved
      histological status of the intestine, and survival. In addition, we investigated
      the effect of Etanercept, a TNF-alpha soluble receptor construct, on ischemia and
      reperfusion injury of the multivisceral organs. Etanercept (5 mg/kg administered
      i.p. 5 min prior to reperfusion) significantly reduced the inflammatory response
      and the ileum injury. Taken together, our results clearly demonstrate that TNF
      alpha plays an important role in the ischemia and reperfusion injury and put
      forward the hypothesis that modulation of TNF-alpha expression may represent a
      novel and possible strategy.

PMID- 17210620
TI  - G2019S LRRK2 mutation causing Parkinson's disease without Lewy bodies.
AB  - The G2019S leucine-rich repeat kinase 2 gene (LRRK2) mutation has been identified
      in a significant proportion of familial and sporadic cases of Parkinson's disease
      (PD). Until now, information on the neuropathological changes associated with the
      G2019S LRRK2 mutation has been sparse. We report a 77-year-old patient who
      presented with a 14 year history of PD but, unexpectedly, histopathological
      examination disclosed mild neuronal loss in the substantia nigra without alpha
      synuclein, tau or ubiquitin cytoplasmic inclusions. A G2019S LRRK2 mutation was
      eventually detected. The present case confirms that clinical PD caused by G2019S
      mutations can be associated with non-specific nigral degeneration without Lewy
      bodies.

PMID- 17210621
TI  - A rare symptomatic presentation of ecchordosis physaliphora: neuroradiological
      and surgical management.
AB  - We report a case of ecchordosis physaliphora, an uncommon benign lesion
      originating from embryonic notochordal remnants, intradurally located in the
      prepontine cistern, that unusually presented associated with symptoms. MRI
      detected and precisely located the small mass. At surgery, a cystic gelatinous
      nodule was found ventral to the pons, contiguous with the dorsal wall of the
      clivus via a small pedicle. Histological examination diagnosed the lesion as an
      ecchordosis physaliphora. Here we focus on the analysis of the neuroradiological
      aspects that play a crucial role from both a diagnostic and a therapeutic
      standpoint.

PMID- 17210622
TI  - Limb ataxia and proximal intracranial territory brain infarcts: clinical and
      topographical correlations.
AB  - BACKGROUND: Limb ataxia is classically attributed to cerebellar hemispheric
      lesions, although isolated lesions of the inferior cerebellar peduncle (ICP) in
      the medulla may also cause this sign. It is still unclear why only some patients
      with acute cerebellar infarcts in the posterior inferior cerebellar artery (PICA)
      territory present with limb ataxia. The proximal intracranial posterior
      circulation (P-PC) territory includes structures fed by the intracranial
      vertebral arteries (ICVAs): the medulla, supplied by small ICVAs branches, and
      posterior inferior portion of the cerebellum, fed by PICA. ICP and PICA territory
      cerebellar infarcts most often occur independently but occasionally occur
      together. OBJECTIVE: To identify structures responsible for limb ataxia in acute
      P-PC brain infarcts, correlating clinical and topographical findings. METHODS:
      Sixteen patients (8 women) were included, aged 30-82 years (mean 62 years), with
      isolated acute strokes in the P-PC territory. RESULTS: The cases reported here
      indicate that limb ataxia in acute P-PC territory infarcts may be associated with
      damage to the ICP in the dorsolateral medulla, regardless of a hemispheric
      cerebellar lesion. In fact, among the nine patients with PICA stroke, limb ataxia
      was observed only in the two patients who also presented damage to the
      dorsolateral medulla involving the ICP. Of the seven patients with isolated
      dorsolateral medullary infarct, only five patients with ICP damage had limb
      ataxia. CONCLUSIONS: When correlating limb ataxia and acute P-PC infarcts, it is
      important to take into account the entire ICVA territory.

PMID- 17210623
TI  - Dementia and leukoencephalopathy due to lymphomatosis cerebri.

PMID- 17210625
TI  - Abnormalities in cortical and peripheral excitability in flail arm variant
      amyotrophic lateral sclerosis.
AB  - BACKGROUND: While some regard the flail arm syndrome as a variant of amyotrophic
      lateral sclerosis (ALS), others have argued that it is a distinct clinical
      entity. Consequently, the present study applied novel central and peripheral
      nerve excitability techniques to further explore disease pathophysiology in flail
      arm syndrome. METHODS: Cortical and peripheral nerve excitability studies were
      undertaken in 11 flail arm patients, defined by muscle weakness limited to the
      proximal aspects of the upper limbs for at least 24 months. RESULTS: Mean age at
      disease onset (60.3 years) was similar to other ALS phenotypes (58.3 years), with
      strong male predominance (male:female distribution: flail arm 10:1; ALS 1.5:1;
      p<0.05) and prolonged disease duration (flail arm 62.5 months; ALS 15.8 months;
      p<0.05). There was evidence of cortical hyperexcitability in flail arm patients,
      similar to findings in ALS, with reduction in short interval intracortical
      inhibition (flail arm 0.8 (0.6)%; ALS 4.1 (1.1)%; controls 8.5 (1.0)%; p<0.0001)
      and resting motor threshold (flail arm 53.4 (2.8)%; ALS 56.6 (1.8)%; controls
      60.7 (1.5)%; p<0.05), along with an increase in motor evoked potential amplitude
      (flail arm 49.5 (9.0)%; ALS 44.4 (4.9)%; controls 25.8 (2.8)%; p<0.05).
      Peripheral nerve excitability studies demonstrated changes consistent with
      upregulation in persistent Na+ currents and reduction of slow K+ conductances,
      similar to findings in ALS. CONCLUSION: This study has demonstrated the presence
      of cortical hyperexcitability in flail arm syndrome, along with abnormalities in
      peripheral nerve excitability, findings consistent with previous studies in other
      ALS phenotypes. By demonstrating the presence of upper motor neuron dysfunction,
      the present study suggests that the flail arm syndrome is an unusual variant of
      ALS.

PMID- 17210624
TI  - Treatment related morbidity of unruptured intracranial aneurysms: results of a
      prospective single centre series with an interdisciplinary approach over a 6 year
      period (1999-2005).
AB  - OBJECTIVES: To review the angiographic and clinical outcome of patients with
      unruptured intracranial aneurysm(s) (UIA) with regard to complications and
      successful obliteration by surgical clipping or endovascular coiling. METHODS:
      Data were derived from a prospective database of intracranial aneurysms from June
      1999 to May 2005. All patients were followed-up for 6 months using the modified
      Rankin Scale (mRS). Favourable outcome was classified as mRS 0-2. From a total of
      691 patients included in the database, 173 harboured 206 UIA of whom 118 patients
      (133 UIA) were treated. RESULTS: Primary treatment assignment was surgical repair
      in 91 UIA and endovascular treatment in 42. In 3 UIA (7.1%), endovascular
      treatment was not feasible and had to be abandoned. Definite treatment was
      surgery in 94 UIA (81 patients) and endovascular obliteration in 39 UIA (37
      patients). There were no deaths related to any treatment. Immediately after
      treatment, 6.4% of the surgical and 7.7% of the endovascular patients showed new
      neurological deficits, mainly related to cerebral ischaemia. After 6 months, 3
      (2.3%) patients had a treatment related unfavourable outcome, defined as mRS >2,
      2 patients after surgical and 1 patient after endovascular aneurysm repair (not
      statistically different, p = 0.3; Fisher's exact test). This led to an overall
      satisfactory outcome in 97.9% of surgically and 97.4% of endovasculary treated
      UIA. After surgical clipping, complete occlusion of the aneurysm was achieved in
      88 (93.6%) and near complete (small residual neck) in 4 (4.3%) of 94 UIA. Two
      small posterior communicating artery aneurysms with a fetal type posterior
      communicating artery were wrapped. After endovascular treatment, obliteration was
      complete in 26 (66.7%). Small residual neck was seen in 13 (33.3%), but none of
      the UIA showed residual aneurysm filling. Five patients in the endovascular group
      (13.9%) underwent repeated endovascular treatment after aneurysm recanalisation.
      CONCLUSIONS: If patients are carefully selected and individually assigned to
      their optimum treatment modality, UIA can be obliterated by surgery or
      endovascular treatment in the majority of patients, with a low percentage of
      unfavourable outcomes. In this series, the outcome was not dependent on
      treatment. However, the rate of recanalisation of UIA is higher after
      endovascular obliteration. After diagnosis of an UIA, an individual
      interdisciplinary decision is essential for each patient to provide the optimum
      management.

PMID- 17210626
TI  - Pathological gambling after bilateral subthalamic nucleus stimulation in
      Parkinson disease.
AB  - We describe a patient with advanced Parkinson's disease who developed
      pathological gambling within a month after successful bilateral subthalamic
      nucleus (STN) stimulation. There was no history of gambling. On
      neuropsychological testing, slight cognitive decline was evident 1 year after
      surgery. Stimulation of the most dorsal contact with and without medication
      induced worse performances on decision making tests compared with the more
      ventral contact. Pathological gambling disappeared after discontinuation of
      pergolide and changing the stimulation parameters. Pathological gambling does not
      seem to be associated with decision making but appears to be related to a
      combination of bilateral STN stimulation and treatment with dopamine agonists.

PMID- 17210628
TI  - Dynamic changes in corticospinal tracts after stroke detected by fibretracking.
AB  - BACKGROUND AND AIMS: The integrity of motor pathways and functional connectivity
      patterns are important in assessing plastic changes related to successful
      recovery, to obtain prognostic information and to monitor future therapeutic
      strategies of stroke patients. We tested the following hypotheses: (1) that
      changes in axonal integrity along the corticospinal tract after stroke can be
      detected as a reduction in fractional anisotropy; and (2) that sustained low
      fractional anisotropy is indicative of axonal loss and therefore is correlated
      with poor motor outcome, as measured by specific neurological motor scores.
      METHODS: We developed a segmentation tool based on magnetic resonance diffusion
      tensor imaging in conjunction with three dimensional fibretracking for
      longitudinal studies of the corticospinal tract, and used specific neurological
      motor scores to test the hypotheses in five stroke patients within the first week
      and 30 and 90 days after the stroke. RESULTS: Reduction in fractional anisotropy
      within the first weeks after stroke reflected a decline in axonal integrity,
      leading to Wallerian degeneration, and demonstrated a correlation between the
      temporal evolution of fractional anisotropy and motor function in patients with
      poor motor outcome. CONCLUSION: The study demonstrated the feasibility of
      fibretracking as a segmentation tool for mapping distal parts of the
      corticospinal motor pathways and showed that fractional anisotropy in the
      segmented corticospinal tract is a sensitive measure of structural changes after
      stroke.

PMID- 17210627
TI  - Risk factor profile of cerebral small vessel disease and its subtypes.
AB  - BACKGROUND: The mechanisms of cerebral small vessel disease (SVD) are unclear.
      Both atherosclerosis and a non-atherosclerotic diffuse arteriopathy have been
      reported pathologically. Two pathological and radiological subtypes have been
      suggested: localised atherosclerotic disease in larger perforating arteries
      causing larger lacunar infarcts without leukoaraiosis, and diffuse disease in
      smaller arterioles causing multiple smaller lacunar infarcts with leukoaraiosis.
      If atherosclerosis were important in SVD as a whole or in one particular subtype,
      one would expect the risk factor profile to be similar to that of cerebral large
      vessel disease (LVD). METHODS: Risk factor profiles were compared in Caucasian
      stroke patients with SVD (n = 414), LVD (n = 471) and 734 stroke-free Caucasian
      population controls. Patients with SVD were subdivided according to the presence
      or absence of confluent leukoaraiosis, into isolated lacunar infarction (ILI) and
      ischaemic leukoaraiosis (ILA). RESULTS: Hypertension was commoner in SVD than LVD
      (odds ratio (OR) 3.43 (2.32 to 5.07); p<0.001) whereas hypercholesterolaemia (OR
      0.34 (0.24 to 0.48); p<0.001), smoking (OR 0.63 (0.44 to 0.91); p = 0.012),
      myocardial infarction (OR 0.35 (0.20 to 0.59); p<0.001) and peripheral vascular
      disease (OR 0.32 (0.20 to 0.50); p<0.001) were commoner in LVD. Among SVD
      patients, age (OR 1.11 (1.09 to 1.14); p<0.001) and hypertension (OR 3.32 (1.56
      to 7.07); p = 0.002) were associated with ILA and hypercholesterolaemia (OR 0.45
      (0.28 to 0.74); p = 0.002), diabetes (OR 0.42 (0.21 to 0.84); p = 0.014) and
      myocardial infarction (OR 0.18 (0.06 to 0.52); p = 0.001) with ILI. CONCLUSION:
      SVD has a different risk factor profile from the typical atherosclerotic profile
      found in LVD, with hypertension being important. There are differences in the
      risk factor profile between the SVD subtypes; the association of ILI with
      hypercholesterolaemia, diabetes and myocardial infarction may be consistent with
      a more atherosclerotic aetiology.

PMID- 17210629
TI  - PINK1, a gene product of PARK6, accumulates in alpha-synucleinopathy brains.

PMID- 17210630
TI  - Hippocampal volume and subcortical white matter lesions in late life depression:
      comparison of early and late onset depression.
AB  - BACKGROUND: Reduced hippocampal volume and increased prevalence of subcortical
      white matter lesions are associated with both recurrent early onset depression
      (EOD) and late onset depression (LOD). It is not clear whether these two factors
      differentially affect the age of onset of first depression. Therefore, we wished
      to investigate the relationship between age of first depression onset and
      hippocampal volume, with adjustment for subcortical white matter lesions.
      METHODS: MRI brain scans were used to compare hippocampal volumes and white
      matter lesions between age matched female patients (>60 years) with recurrent EOD
      and LOD and healthy controls. RESULTS: When comparing the three groups and
      adjusting for age, the Mini-Mental State Examination score, total brain volume
      and total hippocampal volume were significantly smaller in patients with EOD
      compared with controls (5.6 vs 6.1 ml; p = 0.04). The prevalence of larger
      subcortical white matter lesions was higher in patients with LOD compared with
      patients with EOD (47% vs 8%; p = 0.002). Patients with LOD did not differ in
      hippocampal volume from patients with EOD or from controls. CONCLUSIONS: In late
      life depression, age of first depression onset may distinguish between different
      independent neuropathological mechanisms. A small hippocampus volume may be a
      neuroanatomical marker of EOD depression and larger subcortical white matter
      lesions could be an intermediate between cerebrovascular disease and LOD.

PMID- 17210631
TI  - Quantitative proteomics analysis of human endothelial cell membrane rafts:
      evidence of MARCKS and MRP regulation in the sphingosine 1-phosphate-induced
      barrier enhancement.
AB  - Endothelial cell barrier dysfunction results in the increased vascular
      permeability observed in inflammation, tumor metastasis, angiogenesis, and
      atherosclerosis. Sphingosine 1-phosphate (S1P), a biologically active
      phosphorylated lipid growth factor released from activated platelets, enhances
      the endothelial cell barrier integrity in vitro and in vivo. To begin to identify
      the molecular mechanisms mediating S1P induced endothelial barrier enhancement,
      quantitative proteomics analysis (iTRAQ) was performed on membrane rafts isolated
      from human pulmonary artery endothelial cells in the absence or presence of S1P
      stimulation. Our results demonstrated that S1P mediates rapid and specific
      recruitment (1 microM, 5 min) of myristoylated alanine-rich protein kinase C
      substrate (MARCKS) and MARCKS-related protein (MRP) to membrane rafts. Western
      blot experiments confirmed these findings with both MARCKS and MRP. Finally,
      small interfering RNA-mediated silencing of MARCKS or MRP or both attenuates S1P
      mediated endothelial cell barrier enhancement. These data suggest the regulation
      of S1P-mediated endothelial cell barrier enhancement via the cell specific
      localization of MARCKS and MRP and validate the utility of proteomics approaches
      in the identification of novel molecular targets.

PMID- 17210632
TI  - Mechanism of histone H1-stimulated glucocorticoid receptor DNA binding in vivo.
AB  - Xenopus oocytes lack somatic linker histone H1 but contain an oocyte-specific
      variant, B4. The glucocorticoid receptor (GR) inducible mouse mammary tumor virus
      (MMTV) promoter was reconstituted in Xenopus oocytes to address the effects of
      histone H1. The expression of Xenopus H1o [corrected] (H1) via cytoplasmic mRNA
      injection resulted in H1 incorporation into in vivo assembled chromatin based on
      (i) the appearance of a chromatosome stop, (ii) the increased nucleosome repeat
      length (NRL), and (iii) H1-DNA binding assayed by chromatin immunoprecipitation
      (ChIP). The H1 effect on the NRL was saturable and hence represents H1-binding to
      a specific site. A subsaturating level of H1 enhanced the hormone-dependent
      binding of GR to the glucocorticoid response elements (GREs) and the hormone
      dependent MMTV transcription while it reduced the access to DNA as revealed by
      micrococcal nuclease (MNase) analysis. These H1 effects were lost at higher
      levels of H1. ChIP and MNase analysis revealed a hormone-dependent dissociation
      of H1 from the activated chromatin domain. The proposed mechanism of H1-induced
      GR binding is based on two effects: (i) a GR-induced asymmetric distribution of
      H1 in favor of inactive chromatin and (ii) an H1-induced reduction in DNA access.
      These effects results in increased concentration of free GR and, hence, in
      increased GR-GRE binding.

PMID- 17210633
TI  - Distinct structural features of caprin-1 mediate its interaction with G3BP-1 and
      its induction of phosphorylation of eukaryotic translation initiation factor
      2alpha, entry to cytoplasmic stress granules, and selective interaction with a
      subset of mRNAs.
AB  - Caprin-1 is a ubiquitously expressed, well-conserved cytoplasmic phosphoprotein
      that is needed for normal progression through the G(1)-S phase of the cell cycle
      and occurs in postsynaptic granules in dendrites of neurons. We demonstrate that
      Caprin-1 colocalizes with RasGAP SH3 domain binding protein-1 (G3BP-1) in
      cytoplasmic RNA granules associated with microtubules and concentrated in the
      leading and trailing edge of migrating cells. Caprin-1 exhibits a highly
      conserved motif, F(M/I/L)Q(D/E)Sx(I/L)D that binds to the NTF-2-like domain of
      G3BP-1. The carboxy-terminal region of Caprin-1 selectively bound mRNA for c-Myc
      or cyclin D2, this binding being diminished by mutation of the three RGG motifs
      and abolished by deletion of the RGG-rich region. Overexpression of Caprin-1
      induced phosphorylation of eukaryotic translation initiation factor 2alpha (eIF
      2alpha) through a mechanism that depended on its ability to bind mRNA, resulting
      in global inhibition of protein synthesis. However, cells lacking Caprin-1
      exhibited no changes in global rates of protein synthesis, suggesting that
      physiologically, the effects of Caprin-1 on translation were limited to
      restricted subsets of mRNAs. Overexpression of Caprin-1 induced the formation of
      cytoplasmic stress granules (SG). Its ability to bind RNA was required to induce
      SG formation but not necessarily its ability to enter SG. The ability of Caprin-1
      or G3BP-1 to induce SG formation or enter them did not depend on their
      association with each other. The Caprin-1/G3BP-1 complex is likely to regulate
      the transport and translation of mRNAs of proteins involved with synaptic
      plasticity in neurons and cellular proliferation and migration in multiple cell
      types.

PMID- 17210634
TI  - Selective requirements for E2f3 in the development and tumorigenicity of Rb
      deficient chimeric tissues.
AB  - The tumor suppressor function of the retinoblastoma protein pRB is largely
      dependent upon its capacity to inhibit the E2F transcription factors and thereby
      cell proliferation. Attempts to study the interplay between pRB and the E2Fs have
      been hampered by the prenatal death of Rb; E2f nullizygous mice. In this study,
      we isolated Rb; E2f3 mutant embryonic stem cells and generated Rb(-/-); E2f3(-/-)
      chimeric mice, thus bypassing the lethality of the Rb(-/-); E2f3(-/-) germ line
      mutant mice. We show that loss of E2F3 has opposing effects on two of the known
      developmental defects arising in Rb(-/-) chimeras; it suppresses the formation of
      cataracts while aggravating the retinal dysplasia. This model system also allows
      us to assess how E2f3 status influences tumor formation in Rb(-/-) tissues. We
      find that E2f3 is dispensable for the development of pRB-deficient pituitary and
      thyroid tumors. In contrast, E2f3 inactivation completely suppresses the
      pulmonary neuroendocrine hyperplasia arising in Rb(-/-) chimeric mice. This
      hyperproliferative state is thought to represent the preneoplastic lesion of
      small-cell lung carcinoma. Therefore, our observation highlights a potential role
      for E2F3 in the early stages of this tumor type.

PMID- 17210635
TI  - Neuregulin-induced ErbB3 downregulation is mediated by a protein stability
      cascade involving the E3 ubiquitin ligase Nrdp1.
AB  - The molecular mechanisms underlying epidermal growth factor (EGF) receptor
      tyrosine kinase down-regulation in response to growth factor binding are coming
      into focus and involve cbl-mediated receptor ubiquitination followed by lysosomal
      degradation. However, mechanisms underlying the ligand-stimulated degradation of
      the related receptor tyrosine kinases of the ErbB family do not involve cbl and
      remain unexplored. Previous studies have demonstrated that the E3 ubiquitin
      ligase Nrdp1 contributes to the maintenance of steady-state ErbB3 levels by
      mediating its growth factor-independent degradation. Here we demonstrate that
      treatment of cells with the ErbB3 ligand neuregulin-1 (NRG1) stabilizes the
      deubiquitinating enzyme USP8, which in turn stabilizes Nrdp1. The catalytic
      activity of USP8 is required for NRG1-induced Nrdp1 stabilization. We provide
      evidence that Akt-mediated phosphorylation of USP8 threonine residue T907
      contributes to USP8 stability. Finally, we demonstrate that Nrdp1 or USP8
      knockdown suppresses NRG1-induced ErbB3 ubiquitination and degradation in MCF7
      breast cancer cells. We conclude that an NRG1-induced protein stability cascade
      involving USP8 and Nrdp1 mediates the down-regulation of ErbB3. Our observations
      raise the possibility that the ligand-induced augmentation of pathways involved
      in the maintenance of basal levels of receptor tyrosine kinases can contribute to
      ligand-stimulated down-regulation.

PMID- 17210636
TI  - T-cell protein tyrosine phosphatase, distinctively expressed in activated-B-cell
      like diffuse large B-cell lymphomas, is the nuclear phosphatase of STAT6.
AB  - Diffuse large B-cell lymphomas (DLBCLs) consist of clinically distinct subtypes:
      germinal center B-cell (GCB)-like and activated-B-cell (ABC)-like tumors,
      characterized by long and short survival, respectively. We reported distinct
      interleukin 4 (IL-4) responsiveness and STAT6 signaling in these DLBCL subtypes.
      Increased nuclear dephosphorylation of phospho-STAT6 (pSTAT6) was observed in ABC
      like tumors, which exhibited a different expression profile of protein tyrosine
      phosphatases (PTPs). Among the differentially expressed PTPs, only T-cell PTP
      (TCPTP) localizes to the nucleus. Herein, we report that the elevated expression
      of TCPTP in ABC- versus GCB-like DLBCL tumors is not due to the distinct ontogeny
      of these neoplasms but rather may be an acquired feature of the tumors. Moreover,
      we report that STAT6 may serve as a physiological nuclear substrate for TCPTP. We
      demonstrate interactions between endogenous TCPTP and STAT6 and delineate the
      domains responsible for the interaction. Overexpression of TCPTP ameliorates IL-4
      induced STAT6 phosphorylation and associated gene transcription, whereas
      knockdown of endogenous TCPTP results in increased IL-4-induced STAT6 signaling.
      Moreover, we report that TCPTP protein levels may be increased in response to IL
      4 and that TCPTP may serve in a negative feedback loop for the suppression of IL
      4-induced signaling. Taken together, these results identify TCPTP as a
      physiological regulator of STAT6 phosphorylation and suggest that specific
      increases in TCPTP expression in ABC-like DLBCLs may contribute to the different
      biological characteristics of these tumors.

PMID- 17210637
TI  - Identification and characterization of putative tumor suppressor NGB, a GTP
      binding protein that interacts with the neurofibromatosis 2 protein.
AB  - Mutations of the neurofibromatosis 2 (NF2) tumor suppressor gene have frequently
      been detected not only in schwannomas and other central nervous system tumors of
      NF2 patients but also in their sporadic counterparts and malignant tumors
      unrelated to the NF2 syndrome such as malignant mesothelioma, indicating a
      broader role for the NF2 gene in human tumorigenesis. However, the mechanisms by
      which the NF2 product, merlin or schwannomin, is regulated and controls cell
      proliferation remain elusive. Here, we identify a novel GTP-binding protein,
      dubbed NGB (referring to NF2-associated GTP binding protein), which binds to
      merlin. NGB is highly conserved between Saccharomyces cerevisiae, Caenorhabditis
      elegans, and human cells, and its GTP-binding region is very similar to those
      found in R-ras and Rap2. However, ectopic expression of NGB inhibits cell growth,
      cell aggregation, and tumorigenicity in tumorigenic schwanomma cells. Down
      regulation and infrequent mutation of NGB were detected in human glioma cell
      lines and primary tumors. The interaction of NGB with merlin impairs the turnover
      of merlin, yet merlin does not affect the GTPase nor GTP-binding activity of NGB.
      Finally, the tumor suppressor functions of NGB require merlin and are linked to
      its ability to suppress cyclin D1 expression. Collectively, these findings
      indicate that NGB is a tumor suppressor that regulates and requires merlin to
      suppress cell proliferation.

PMID- 17210638
TI  - Calpain 6 is involved in microtubule stabilization and cytoskeletal organization.
AB  - The calpains are a family of Ca(2+)-dependent cysteine proteases implicated in
      various biological processes. In this family, calpain 6 (Capn6) is unique in that
      it lacks the active-site cysteine residues requisite for protease activity.
      During the search for genes downstream of the endothelin 1 (ET-1) signaling in
      pharyngeal-arch development, we identified Capn6. After confirming that the
      expression of Capn6 in pharyngeal arches is downregulated in ET-1-null embryos by
      in situ hybridization, we investigated its function. In Capn6-transfected cells,
      cytokinesis was retarded and was often aborted to yield multinucleated cells.
      Capn6 overexpression also caused the formation of microtubule bundles rich in
      acetylated alpha-tubulin and resistant to the depolymerizing activity of
      nocodazole. Green fluorescent protein-Capn6 overexpression, immunostaining for
      endogenous Capn6, and biochemical analysis demonstrated interaction between Capn6
      and microtubules, which appeared to be mainly mediated by domain III.
      Furthermore, RNA interference-mediated Capn6 inactivation caused microtubule
      instability with a loss of acetylated alpha-tubulin and induced actin
      reorganization, resulting in lamellipodium formation with membrane ruffling.
      Taken together, these results indicate that Capn6 is a microtubule-stabilizing
      protein expressed in embryonic tissues that may be involved in the regulation of
      microtubule dynamics and cytoskeletal organization.

PMID- 17210639
TI  - Pref-1 (preadipocyte factor 1) activates the MEK/extracellular signal-regulated
      kinase pathway to inhibit adipocyte differentiation.
AB  - Preadipocyte factor 1 (Pref-1) is found in preadipocytes but is absent in
      adipocytes. Pref-1 is made as a transmembrane protein but is cleaved to generate
      a biologically active soluble form. Although Pref-1 inhibition of adipogenesis
      has been well studied in vitro and in vivo, the signaling pathway for Pref-1 is
      not known. Here, by using purified soluble Pref-1 in Pref-1 null mouse embryo
      fibroblasts (MEF), we show that Pref-1 increases MEK/extracellular signal
      regulated kinase (ERK) phosphorylation in a time- and dose-dependent manner.
      Compared to wild-type MEF, differentiation of Pref-1 null MEF into adipocytes is
      enhanced, as judged by lipid accumulation and adipocyte marker expression. Both
      wild-type and Pref-1 null MEF show a transient burst of ERK phosphorylation upon
      addition of adipogenic agents. Wild-type MEF show a significant, albeit lower,
      second increase in ERK phosphorylation peaking at day 2. This ERK
      phosphorylation, corresponding to Pref-1 abundance, is absent during
      differentiation of Pref-1 null MEF. Prevention of this second increase in ERK1/2
      phosphorylation in wild-type MEF by the MEK inhibitor PD98059 or by transient
      depletion of ERK1/2 via small interfering RNA-enhanced adipocyte differentiation.
      Furthermore, treatment of Pref-1 null MEF with Pref-1 restores this ERK
      phosphorylation, resulting in inhibition of adipocyte differentiation primarily
      by preventing peroxisome proliferator-activated receptor gamma2 induction.
      However, in the presence of PD98059 or depletion of ERK1/2, exogenous Pref-1
      cannot inhibit adipocyte differentiation in Pref-1 null MEF. We conclude that
      Pref-1 activates MEK/ERK signaling, which is required for Pref-1 inhibition of
      adipogenesis.

PMID- 17210640
TI  - The N terminus of Drosophila ESC binds directly to histone H3 and is required for
      E(Z)-dependent trimethylation of H3 lysine 27.
AB  - Polycomb group proteins mediate heritable transcriptional silencing and function
      through multiprotein complexes that methylate and ubiquitinate histones. The 600
      kDa E(Z)/ESC complex, also known as Polycomb repressive complex 2 (PRC2),
      specifically methylates histone H3 lysine 27 (H3 K27) through the intrinsic
      histone methyltransferase (HMTase) activity of the E(Z) SET domain. By itself,
      E(Z) exhibits no detectable HMTase activity and requires ESC for methylation of
      H3 K27. The molecular basis for this requirement is unknown. ESC binds directly,
      via its C-terminal WD repeats (beta-propeller domain), to E(Z). Here, we show
      that the N-terminal region of ESC that precedes its beta-propeller domain
      interacts directly with histone H3, thereby physically linking E(Z) to its
      substrate. We show that when expressed in stable S2 cell lines, an N-terminally
      truncated ESC (FLAG-ESC61-425), like full-length ESC, is incorporated into
      complexes with E(Z) and binds to a Ubx Polycomb response element in a chromatin
      immunoprecipitation assay. However, incorporation of this N-terminally truncated
      ESC into E(Z) complexes prevents trimethylation of histone H3 by E(Z). We also
      show that a closely related Drosophila melanogaster paralog of ESC, ESC-like
      (ESCL), and the mammalian homolog of ESC, EED, also interact with histone H3 via
      their N termini, indicating that the interaction of ESC with histone H3 is
      evolutionarily conserved, reflecting its functional importance. Our data suggest
      that one of the roles of ESC (and ESCL and EED) in PRC2 complexes is to enable
      E(Z) to utilize histone H3 as a substrate by physically linking enzyme and
      substrate.

PMID- 17210641
TI  - Hepatic de novo lipogenesis is present in liver-specific ACC1-deficient mice.
AB  - Acetyl coenzyme A (acetyl-CoA) carboxylase (ACC) catalyzes carboxylation of
      acetyl-CoA to form malonyl-CoA. In mammals, two isozymes exist with distinct
      physiological roles: cytosolic ACC1 participates in de novo lipogenesis (DNL),
      and mitochondrial ACC2 is involved in negative regulation of mitochondrial beta
      oxidation. Since systemic ACC1 null mice were embryonic lethal, to clarify the
      physiological role of ACC1 in hepatic DNL, we generated the liver-specific ACC1
      null mouse by crossbreeding of an Acc1(lox(ex46)) mouse, in which exon 46 of Acc1
      was flanked by two loxP sequences and the liver-specific Cre transgenic mouse. In
      liver-specific ACC1 null mice, neither hepatic Acc1 mRNA nor protein was
      detected. However, to compensate for ACC1 function, hepatic ACC2 protein and
      activity were induced 1.4 and 2.2 times, respectively. Surprisingly, hepatic DNL
      and malonyl-CoA were maintained at the same physiological levels as in wild-type
      mice. Furthermore, hepatic DNL was completely inhibited by an ACC1/2 dual
      inhibitor, 5-tetradecyloxyl-2-furancarboxylic acid. These results strongly
      demonstrate that malonyl-CoA from ACC2 can access fatty acid synthase and become
      the substrate for the DNL pathway under the unphysiological circumstances that
      result with ACC1 disruption. Therefore, there does not appear to be strict
      compartmentalization of malonyl-CoA from either of the ACC isozymes in the liver.

PMID- 17210642
TI  - The Bloom's syndrome helicase is critical for development and function of the
      alphabeta T-cell lineage.
AB  - Bloom's syndrome is a genetic disorder characterized by increased incidence of
      cancer and an immunodeficiency of unknown origin. The BLM gene mutated in Bloom's
      syndrome encodes a DNA helicase involved in the maintenance of genomic integrity.
      To explore the role of BLM in the immune system, we ablated murine Blm in the T
      cell lineage. In the absence of Blm, thymocytes were severely reduced in numbers
      and displayed a developmental block at the beta-selection checkpoint that was
      partially p53 dependent. Blm-deficient thymocytes rearranged their T-cell
      receptor (TCR) beta genes normally yet failed to survive and proliferate in
      response to pre-TCR signaling. Furthermore, peripheral T cells were reduced in
      numbers, manifested defective homeostatic and TCR-induced proliferation, and
      produced extensive chromosomal damage. Finally, CD4(+) and CD8(+) T-cell
      responses were impaired upon antigen challenge. Thus, by ensuring genomic
      stability, Blm serves a vital role for development, maintenance, and function of
      T lymphocytes, suggesting a basis for the immune deficiency in Bloom's syndrome.

PMID- 17210643
TI  - Direct role for the Rpd3 complex in transcriptional induction of the anaerobic
      DAN/TIR genes in yeast.
AB  - Saccharomyces cerevisiae adapts to hypoxia by expressing a large group of
      "anaerobic" genes. Among these, the eight DAN/TIR genes are regulated by the
      repressors Rox1 and Mot3 and the activator Upc2/Mox4. In attempting to identify
      factors recruited by the DNA binding repressor Mot3 to enhance repression of the
      DAN/TIR genes, we found that the histone deacetylase and global repressor
      complex, Rpd3-Sin3-Sap30, was not required for repression. Strikingly, the
      complex was instead required for activation. In addition, the histone H3 and H4
      amino termini, which are targets of Rpd3, were also required for DAN1 expression.
      Epistasis tests demonstrated that the Rpd3 complex is not required in the absence
      of the repressor Mot3. Furthermore, the Rpd3 complex was required for normal
      function and stable binding of the activator Upc2 at the DAN1 promoter. Moreover,
      the Swi/Snf chromatin remodeling complex was strongly required for activation of
      DAN1, and chromatin immunoprecipitation analysis showed an Rpd3-dependent
      reduction in DAN1 promoter-associated nucleosomes upon induction. Taken together,
      these data provide evidence that during anaerobiosis, the Rpd3 complex acts at
      the DAN1 promoter to antagonize the chromatin-mediated repression caused by Mot3
      and Rox1 and that chromatin remodeling by Swi/Snf is necessary for normal
      expression.

PMID- 17210644
TI  - The new core promoter element XCPE1 (X Core Promoter Element 1) directs activator
      , mediator-, and TATA-binding protein-dependent but TFIID-independent RNA
      polymerase II transcription from TATA-less promoters.
AB  - The core promoter is a critical DNA element required for accurate transcription
      and regulation of transcription. Several core promoter elements have been
      previously identified in eukaryotes, but those cannot account for transcription
      from most RNA polymerase II-transcribed genes. Additional, as-yet-unidentified
      core promoter elements must be present in eukaryotic genomes. From extensive
      analyses of the hepatitis B virus X gene promoter, here we identify a new core
      promoter element, XCPE1 (the X gene core promoter element 1), that drives RNA
      polymerase II transcription. XCPE1 is located between nucleotides -8 and +2
      relative to the transcriptional start site (+1) and has a consensus sequence of
      G/A/T-G/C-G-T/C-G-G-G/A-A-G/C(+1)-A/C. XCPE1 shows fairly weak transcriptional
      activity alone but exerts significant, specific promoter activity when
      accompanied by activator-binding sites. XCPE1 is also found in the core promoter
      regions of about 1% of human genes, particularly in poorly characterized TATA
      less genes. Our in vitro transcription studies suggest that the XCPE1-driven
      transcription can be highly active in the absence of TFIID because it can utilize
      either free TBP or the complete TFIID complex. Our findings suggest the
      possibility of the existence of a TAF1 (TFIID)-independent transcriptional
      initiation mechanism that may be used by a category of TATA-less promoters in
      higher eukaryotes.

PMID- 17210645
TI  - CTCF interacts with and recruits the largest subunit of RNA polymerase II to CTCF
      target sites genome-wide.
AB  - CTCF is a transcription factor with highly versatile functions ranging from gene
      activation and repression to the regulation of insulator function and imprinting.
      Although many of these functions rely on CTCF-DNA interactions, it is an emerging
      realization that CTCF-dependent molecular processes involve CTCF interactions
      with other proteins. In this study, we report the association of a subpopulation
      of CTCF with the RNA polymerase II (Pol II) protein complex. We identified the
      largest subunit of Pol II (LS Pol II) as a protein significantly colocalizing
      with CTCF in the nucleus and specifically interacting with CTCF in vivo and in
      vitro. The role of CTCF as a link between DNA and LS Pol II has been reinforced
      by the observation that the association of LS Pol II with CTCF target sites in
      vivo depends on intact CTCF binding sequences. "Serial" chromatin
      immunoprecipitation (ChIP) analysis revealed that both CTCF and LS Pol II were
      present at the beta-globin insulator in proliferating HD3 cells but not in
      differentiated globin synthesizing HD3 cells. Further, a single wild-type CTCF
      target site (N-Myc-CTCF), but not the mutant site deficient for CTCF binding, was
      sufficient to activate the transcription from the promoterless reporter gene in
      stably transfected cells. Finally, a ChIP-on-ChIP hybridization assay using
      microarrays of a library of CTCF target sites revealed that many intergenic CTCF
      target sequences interacted with both CTCF and LS Pol II. We discuss the possible
      implications of our observations with respect to plausible mechanisms of
      transcriptional regulation via a CTCF-mediated direct link of LS Pol II to the
      DNA.

PMID- 17210646
TI  - Cyclic AMP stimulates SF-1-dependent CYP11A1 expression through homeodomain
      interacting protein kinase 3-mediated Jun N-terminal kinase and c-Jun
      phosphorylation.
AB  - Steroids are synthesized in adrenal glands and gonads under the control of
      pituitary peptides. These peptides bind to cell surface receptors to activate the
      cyclic AMP (cAMP) signaling pathway leading to an increase of steroidogenic gene
      expression. Exactly how cAMP activates steroidogenic gene expression is not
      clear, except for the knowledge that transcription factor SF-1 plays a key role.
      Investigating the factors participating in SF-1 action, we found that c-Jun and
      homeodomain-interacting protein kinase 3 (HIPK3) were required for basal and cAMP
      stimulated expression of one major steroidogenic gene, CYP11A1. HIPK3 enhanced SF
      1 activity, and c-Jun was required for the functional interaction of HIPK3 with
      SF-1. Furthermore, after cAMP stimulation, both c-Jun and Jun N-terminal kinase
      (JNK) were phosphorylated through HIPK3. These phosphorylations were important
      for SF-1 activity and CYP11A1 expression. Thus, we have defined HIPK3-mediated
      JNK activity and c-Jun phosphorylation as important events that increase SF-1
      activity for CYP11A1 transcription in response to cAMP. This finding has linked
      three common factors, HIPK3, JNK, and c-Jun, to the cAMP signaling pathway
      leading to increased steroidogenic gene expression.

PMID- 17210647
TI  - Structure/function analysis of Xenopus cryptochromes 1 and 2 reveals differential
      nuclear localization mechanisms and functional domains important for interaction
      with and repression of CLOCK-BMAL1.
AB  - Circadian rhythms control the temporal arrangement of molecular, physiological,
      and behavioral processes within an organism and also synchronize these processes
      with the external environment. A cell autonomous molecular oscillator, consisting
      of interlocking transcriptional/translational feedback loops, drives the
      approximately 24-hour duration of these rhythms. The cryptochrome protein (CRY)
      plays a central part in the negative feedback loop of the molecular clock by
      translocating to the nucleus and repressing CLOCK and BMAL1, two transcription
      factors that comprise the positive elements in this cycle. In order to gain
      insight into the inner workings of this feedback loop, we investigated the
      structure/function relationships of Xenopus laevis CRY1 (xCRY1) and xCRY2 in
      cultured cells. The C-terminal tails of both xCRY1 and xCRY2 are sufficient for
      their nuclear localization but achieve it by different mechanisms. Through the
      generation and characterization of xCRY/photolyase chimeras, we found that the
      second half of the photolyase homology region (PHR) of CRY is important for
      repression through facilitating interaction with BMAL1. Characterization of these
      functional domains in CRYs will help us to better understand the mechanism of the
      known roles of CRYs and to elucidate new intricacies of the molecular clock.

PMID- 17210648
TI  - A triple helix within a pseudoknot is a conserved and essential element of
      telomerase RNA.
AB  - Telomerase copies a short template within its integral telomerase RNA onto
      eukaryotic chromosome ends, compensating for incomplete replication and
      degradation. Telomerase action extends the proliferative potential of cells, and
      thus it is implicated in cancer and aging. Nontemplate regions of telomerase RNA
      are also crucial for telomerase function. However, they are highly divergent in
      sequence among species, and their roles are largely unclear. Using in silico
      three-dimensional modeling, constrained by mutational analysis, we propose a
      three-dimensional model for a pseudoknot in telomerase RNA of the budding yeast
      Kluyveromyces lactis. Interestingly, this structure includes a U-A.U major-groove
      triple helix. We confirmed the triple-helix formation in vitro using
      oligoribonucleotides and showed that it is essential for telomerase function in
      vivo. While triplex-disrupting mutations abolished telomerase function, triple
      compensatory mutations that formed pH-dependent G-C.C(+) triples restored the
      pseudoknot structure in a pH-dependent manner and partly restored telomerase
      function in vivo. In addition, we identified a novel type of triple helix that is
      formed by G-C.U triples, which also partly restored the pseudoknot structure and
      function. We propose that this unusual structure, so far found only in telomerase
      RNA, provides an essential and conserved telomerase-specific function.

PMID- 17210649
TI  - PAG-associated FynT regulates calcium signaling and promotes anergy in T
      lymphocytes.
AB  - Phosphoprotein associated with glycolipid-enriched membranes (PAG), also named
      Csk-binding protein (Cbp), is a transmembrane adaptor associated with lipid
      rafts. It is phosphorylated on multiple tyrosines located in the cytoplasmic
      domain. One tyrosine, tyrosine 314 (Y314) in the mouse, interacts with Csk, a
      protein tyrosine kinase that negatively regulates Src kinases. This interaction
      enables PAG to inhibit T-cell antigen receptor (TCR)-mediated T-cell activation.
      PAG also associates with the Src-related kinase FynT. Genetic studies indicated
      that FynT was required for PAG tyrosine phosphorylation and binding of PAG to Csk
      in T cells. Herein, we investigated the function and regulation of PAG-associated
      FynT. Our data showed that PAG was constitutively associated with FynT in
      unstimulated T cells and that this association was rapidly lost in response to
      TCR stimulation. Dissociation of the PAG-FynT complex preceded PAG
      dephosphorylation and PAG-Csk dissociation after TCR engagement. Interestingly,
      in anergic T cells, the association of PAG with FynT, but not Csk, was increased.
      Analyses of PAG mutants provided evidence that PAG interacted with FynT by way of
      tyrosines other than Y314. Enforced expression of a PAG variant interacting with
      FynT, but not Csk, caused a selective enhancement of TCR-triggered calcium fluxes
      in normal T cells. Furthermore, it promoted T-cell anergy. Both effects were
      absent in mice lacking FynT, implying that the effects were mediated by PAG
      associated FynT. Hence, besides enabling PAG tyrosine phosphorylation and the PAG
      Csk interaction, PAG-associated FynT can stimulate calcium signals and favor T
      cell anergy. These data improve our comprehension of the function of PAG in T
      cells. They also further implicate FynT in T-cell anergy.

PMID- 17210650
TI  - Linker histone HIS-24 (H1.1) cytoplasmic retention promotes germ line development
      and influences histone H3 methylation in Caenorhabditis elegans.
AB  - RNA interference with one of the eight Caenorhabditis elegans linker histone
      genes triggers desilencing of a repetitive transgene and developmental defects in
      the hermaphrodite germ line. These characteristics are similar to the phenotype
      of the C. elegans Polycomb group genes mes-2, mes-3, mes-4, and mes-6 (M. A.
      Jedrusik and E. Schulze, Development 128:1069-1080, 2001; I. Korf, Y. Fan, and S.
      Strome, Development 125:2469-2478, 1998). These Polycomb group proteins
      contribute to germ line-specific chromatin modifications. Using a his-24 deletion
      mutant and an isoform-specific antibody, we characterized the role of his-24 in
      C. elegans germ line development. We describe an unexpected cytoplasmic retention
      of HIS-24 in peculiar granular structures. This phenomenon is confined to the
      developing germ lines of both sexes. It is strictly dependent on the activities
      of the chromatin-modifying genes mes-2, mes-3, mes-4, and mes-6, as well as on
      the C. elegans sirtuin gene sir-2.1. A temperature shift experiment with a mes
      3(ts) mutant revealed that mes gene activity is required in a time window ranging
      from L3 to the early L4 stage before the onset of meiosis. We find that the his
      24(ok1024) mutant germ line is characterized by an increased level of the
      activating H3K4 methylation mark concomitant with a decrease of the repressive
      H3K9 methylation. In the germ line of his-24(ok1024) mes-3(bn35) double mutant
      animals, the repressive H3K27 methylation is more reduced than in the respective
      mes single mutant. These observations distinguish his-24 as an unusual element in
      the developmental regulation of germ line chromatin structure in C. elegans.

PMID- 17210652
TI  - Developing comparative criminology and the case of China: an introduction.
AB  - Although comparative criminology has made significant development during the past
      decade or so, systematic empirical research has only developed along a few
      topics. Comparative criminology has never occupied a central position in
      criminology. This article analyzes the major theoretical and methodological
      impediments in the development of comparative criminology. It stresses a need to
      shift methodology from a conventional primary approach that uses the nation as
      the unit of analysis to an in-depth case study method as a primary methodological
      approach. The article maintains that case study method can overcome the
      limitation of its descriptive tradition and become a promising methodological
      approach for comparative criminology.

PMID- 17210653
TI  - Life strain, coping, and delinquency in the People's Republic of China: an
      empirical test of general strain theory from a matching perspective in social
      support.
AB  - Using a sample of 615 middle- and high-school students from rural and urban areas
      of the People's Republic of China, this study tests the effects of coping
      strategies predicted by Agnew's (1992) general strain theory (GST), in which the
      impact of strain on delinquency is conditioned by adolescents' social and
      personal resources. Results provide support for the coping strategies hypotheses
      posited by GST, in a non-Western culture. Social supports in the three major
      domains of family, school, and peer group have cross-domain and within-domain
      buffering effects on the relationships between juvenile delinquency and
      interpersonal problems in these domains, and moral beliefs have all-domain
      buffering effects. Girls are more likely to use cross-domain support resources in
      managing interpersonal problems, whereas boys are more susceptible to delinquent
      peers in their adaptation to interpersonal strain in all domains. The
      implications of the findings to intervention were discussed.

PMID- 17210651
TI  - Role of cytochrome C in apoptosis: increased sensitivity to tumor necrosis factor
      alpha is associated with respiratory defects but not with lack of cytochrome C
      release.
AB  - Although the role of cytochrome c in apoptosis is well established, details of
      its participation in signaling pathways in vivo are not completely understood.
      The knockout for the somatic isoform of cytochrome c caused embryonic lethality
      in mice, but derived embryonic fibroblasts were shown to be resistant to
      apoptosis induced by agents known to trigger the intrinsic apoptotic pathway. In
      contrast, these cells were reported to be hypersensitive to tumor necrosis factor
      alpha (TNF-alpha)-induced apoptosis, which signals through the extrinsic pathway.
      Surprisingly, we found that this cell line (CRL 2613) respired at close to normal
      levels because of an aberrant activation of a testis isoform of cytochrome c,
      which, albeit expressed at low levels, was able to replace the somatic isoform
      for respiration and apoptosis. To produce a bona fide cytochrome c knockout, we
      developed a mouse knockout for both the testis and somatic isoforms of cytochrome
      c. The mouse was made viable by the introduction of a ubiquitously expressed
      cytochrome c transgene flanked by loxP sites. Lung fibroblasts in which the
      transgene was deleted showed no cytochrome c expression, no respiration, and
      resistance to agents that activate the intrinsic and to a lesser but significant
      extent also the extrinsic pathways. Comparison of these cells with lines with a
      defective oxidative phosphorylation system showed that cells with defective
      respiration have increased sensitivity to TNF-alpha-induced apoptosis, but this
      process was still amplified by cytochrome c. These studies underscore the
      importance of oxidative phosphorylation and apoptosome function to both the
      intrinsic and extrinsic apoptotic pathways.

PMID- 17210654
TI  - Provincial laws on the protection of women in China: a partial test of Black's
      theory.
AB  - Using data extracted from 29 provincial laws on the protection of women in China
      promulgated during the 1980s, this study tests Black's (1976) proposition that
      the quantity of law varies with stratification, morphology, culture,
      organization, and social control. Analyses yielded little support for Black's
      propositions except significant direct relationships between morphology and the
      quantity of five types of provincial laws. The article concludes with a
      discussion of alternative explanations for the observed findings and the
      implications of this research for further studies on the development of law.

PMID- 17210655
TI  - Returning to normality: anomie and crime in China.
AB  - The current study explored the value change as manifested in the sense of anomie
      during the 1990s and sources of anomie in contemporary China. The multiple
      regression analysis found that employment, having children, and satisfaction in
      life were significantly related to anomie; however, the effect of education was
      related to anomie in the direction that was inconsistent with what was known in
      the Western literature. Age had no significant effect on anomie. It is concluded
      that the crime rates remain relatively low even after many years of dramatic
      increase, and that China may not be able to maintain its tight control over
      politics forever.

PMID- 17210656
TI  - Building little safe and civilized communities: community crime prevention with
      Chinese characteristics?
AB  - This article describes a community crime prevention program in China, set against
      a background of rapid economic development, large internal population migration,
      and increasing crime rates. Traditional social control in China has been
      transformed to adapt to the new reform era, yet some mechanisms remain intact.
      Crime prevention measures and strategies resemble those adopted in the West;
      however, the differences, constituting the so-called Chinese characteristics with
      community crime prevention are significant.

PMID- 17210657
TI  - Bureaucratic justice: the incarceration of mainland Chinese women working in Hong
      Kong's sex industry.
AB  - Since Hong Kong's return to the People's Republic of China (PRC) there has been a
      significant rise in the number of Chinese visitors to Hong Kong, including women
      crossing the border to engage in sex work. Sex work itself is not a crime in Hong
      Kong, but related activities, like soliciting, are prohibited. Sex work is
      treated as work for immigration purposes, and visitors who engage in work without
      an employment visa are breaching their conditions of stay. More than 10,000
      mainland Chinese women have been arrested, prosecuted, and sentenced in recent
      years, causing the correctional population to expand beyond capacity. The authors
      examine the experiences of 58 incarcerated women in their encounters with the
      Hong Kong criminal justice system and find that women are processed in a highly
      routinized bureaucratic manner. They consider the purpose served by the largely
      bureaucratic form of justice that has emerged in response to migrant sex workers
      in Hong Kong.

PMID- 17210658
TI  - Capital punishment views in China and the United States: a preliminary study
      among college students.
AB  - There is a lack of research on attitudes toward capital punishment in China, and
      there is even less research on cross-national comparisons of capital punishment
      views. Using data recently collected from college students in the United States
      and China, this study finds that U.S. and Chinese students have differences in
      their views on the death penalty and its functions of deterrence, rehabilitation,
      and incapacitation. This study also reveals that the respondents' perspectives of
      deterrence, rehabilitation, retribution, and incapacitation all affect their
      attitudes toward the death penalty in the United States, whereas only the first
      three views affect attitudes toward capital punishment in China. Furthermore,
      retribution is the strongest predictor in the United States, whereas deterrence
      is the strongest predictor in China.

PMID- 17210659
TI  - Drug problems in China: recent trends, countermeasures, and challenges.
AB  - Drug crime in China is on an overall rising trend. Major drug crime cases are
      becoming more common, the types of drugs being trafficked are more diverse, and
      the smuggling and trafficking of drugs into the country and the smuggling of
      precursor chemicals out of the country have formed a bidirectional cycle. Drug
      crimes in China have also begun to show a conspicuous trend of
      internationalization. China's main countermeasures against drug crimes have been
      to pass new laws and regulations against drugs, to increase the efforts to
      eradicate cultivation, to establish and expand "drug-free communities" programs,
      and to strengthen international cooperation in antidrug campaigns. The existing
      problems demand prompt solutions, which include a shortage of funding and lack of
      accurate knowledge about prevalence of drug abuse and related data for
      scientifically studying the drug problems.

PMID- 17210660
TI  - Criminological research in contemporary China: challenges and lessons learned
      from a large-scale criminal victimization survey.
AB  - This article discusses research experience gained from a large-scale survey of
      criminal victimization recently conducted in Tianjin, China. The authors review
      some of the more important challenges that arose in the research, their responses
      to these challenges, and lessons learned that might be beneficial to other
      scholars who are interested in conducting criminological research in China. Their
      experience underscores the importance of understanding the Chinese political,
      cultural, and academic context, and the utility of collaborating with experienced
      and knowledgeable colleagues "on site." Although there are some special
      difficulties and barriers, their project demonstrates the feasibility of original
      criminological data collection in China.

PMID- 17210661
TI  - Peritoneal lavage cells of Indonesian thin-tail sheep mediate antibody-dependent
      superoxide radical cytotoxicity in vitro against newly excysted juvenile Fasciola
      gigantica but not juvenile Fasciola hepatica.
AB  - Indonesian thin-tail (ITT) sheep resist infection by Fasciola gigantica by an
      immunological mechanism within 2 to 4 weeks of infection yet are susceptible to
      F. hepatica infection. Studies of ITT sheep show that little liver damage occurs
      following F. gigantica infection, suggesting that the invading parasites are
      killed within the peritoneum or shortly after reaching the liver. We investigated
      whether cells isolated from the peritoneums of ITT sheep could kill newly
      excysted juvenile F. gigantica in vitro and act as a potential mechanism of
      resistance against F. gigantica infection. Peritoneal cells from F. gigantica
      infected sheep, rich in macrophages and eosinophils, mediated antibody-dependent
      cytotoxicity against juvenile F. gigantica in vitro. Cytotoxicity was dependent
      on contact between the parasite and effector cells. Isolated mammary gland
      eosinophils of F. gigantica-infected sheep, or resident peritoneal
      monocytes/macrophages from uninfected sheep, also killed the juvenile parasites
      in vitro. By using inhibitors, we show that the molecular mechanism of killing in
      these assays was dependent on the production of superoxide radicals by
      macrophages and eosinophils. In contrast, this cytotoxic mechanism was
      ineffective against juvenile F. hepatica parasites in vitro. Analysis of
      superoxide dismutase activity and mRNA levels showed that activity and gene
      expression were higher in F. hepatica than in F. gigantica, suggesting a possible
      role for this enzyme in the resistance of F. hepatica to superoxide-mediated
      killing. We suggest that ovine macrophages and eosinophils, acting in concert
      with a specific antibody, may be important effector cells involved in the
      resistance of ITT sheep to F. gigantica.

PMID- 17210662
TI  - Echinococcus granulosus antigen B impairs human dendritic cell differentiation
      and polarizes immature dendritic cell maturation towards a Th2 cell response.
AB  - Despite inducing a strong host cellular and humoral immune response, the helminth
      Echinococcus granulosus is a highly successful parasite that develops,
      progresses, and ultimately causes chronic disease. Although surgery remains the
      preferred therapeutic option, pharmacological research now envisages
      antihelminthic strategies. To understand the mechanisms that E. granulosus uses
      to escape host immunosurveillance and promote chronic infection, we investigated
      how two hydatid cyst components, purified antigen B (AgB) and sheep hydatid fluid
      (SHF), act on host dendritic cell (DC) differentiation from monocyte precursors
      and how they influence maturation of DC that have already differentiated. We
      evaluated the immunomodulatory potential of these antigens by performing
      immunochemical and cytofluorimetric analyses of monocyte-derived DCs from healthy
      human donors. During monocyte differentiation, AgB and SHF downmodulated CD1a
      expression and upregulated CD86 expression. Compared with immature DCs
      differentiated in medium alone (iDCs), AgB- and SHF-differentiated cells
      stimulated with lipopolysaccharide included a significantly lower percentage of
      CD83(+) cells (P < 10(-4)) and had weaker costimulatory molecule expression. When
      stimulated with AgB and SHF, iDCs matured and primed lymphocytes towards the Th2
      response typical of E. granulosus infection. SHF and particularly AgB reduced the
      production of interleukin-12p70 (IL-12p70) and tumor necrosis factor alpha in
      lipopolysaccharide-stimulated iDCs. Anti-IL-10 antibodies increased the levels of
      IL-12p70 secretion in AgB- and SHF-matured DCs. AgB and SHF induced interleukin-1
      receptor-associated kinase phosphorylation and activated nuclear factor-kappaB,
      suggesting that Toll-like receptors could participate in E. granulosus-stimulated
      DC maturation. These results suggest that E. granulosus escapes host
      immunosurveillance in two ways: by interfering with monocyte differentiation and
      by modulating DC maturation.

PMID- 17210663
TI  - Rat model of polymicrobial infection, immunity, and alveolar bone resorption in
      periodontal disease.
AB  - One of the predominant polymicrobial infections of humans is expressed clinically
      as periodontal disease. Porphyromonas gingivalis, Treponema denticola, and
      Tannerella forsythia have been strongly implicated as members of a pathogenic
      consortium in the etiology of adult periodontitis. In this study we hypothesized
      that P. gingivalis, T. denticola, and T. forsythia are synergistic in terms of
      virulence potential and induce chronic periodontal inflammation that leads to
      alveolar bone resorption in a polymicrobial infection in rats. Groups of rats
      were infected with either P. gingivalis, T. denticola, or T. forsythia in
      monomicrobial infections or with all three species in polymicrobial oral
      infections with or without Fusobacterium nucleatum. PCR analyses of oral
      microbial samples demonstrated that rats infected with one bacterium were orally
      colonized by each of the bacteria during the study interval, and increased serum
      immunoglobulin G (IgG) antibody levels substantiated the interaction of the host
      with the infecting bacteria. PCR analyses of the rats with polymicrobial
      infections demonstrated that most rats were infected with P. gingivalis, T.
      denticola, and T. forsythia as a consortium. Furthermore, all rats exhibited a
      significant increase in the level of IgG antibody to the polymicrobial
      consortium. Radiographic measurement of alveolar bone resorption showed that rats
      infected with the polymicrobial consortium with or without F. nucleatum exhibited
      significantly increased alveolar bone resorption compared to the resorption in
      uninfected control rats, as well as the resorption in rats infected with one of
      the microbes. These results documented that P. gingivalis, T. denticola, and T.
      forsythia not only exist as a consortium that is associated with chronic
      periodontitis but also exhibit synergistic virulence resulting in the
      immunoinflammatory bone resorption characteristic of periodontitis.

PMID- 17210664
TI  - Transcriptional and proteomic profiles of group B Streptococcus type V reveal
      potential adherence proteins associated with high-level invasion.
AB  - Group B Streptococcus (GBS) is an opportunistic organism that can harmlessly
      colonize the human gut, vagina, and rectum but can also cause pneumonia, sepsis,
      and meningitis in neonates born to colonized mothers. We have shown previously
      that growth rate and oxygen level regulate the ability of GBS to invade
      eukaryotic cells in vitro. Herein we extend and expand on these observations to
      show that GBS type V, an emergent serotype, grown in a chemostat at a cell mass
      doubling time (t(d)) of 1.8 h with oxygen invaded human ME-180 cervical
      epithelial cells in large numbers compared with those grown at the same t(d)
      without oxygen or at a slower t(d) of 11.0 h. The fact that several GBS type V
      cell wall-associated and membrane proteins were expressed exclusively under the
      invasive growth condition prompted an investigation, using genomics and
      proteomics, of all upregulated genes and proteins. Several proteins with
      potential roles in adherence were identified, including an undefined surface
      antigen (SAG1350), a lipoprotein (SAG0971), penicillin-binding protein 2b
      (SAG0765), glyceraldehyde-3-phosphate dehydrogenase (SAG0823), and an iron
      binding protein (SAG1007). Mouse antisera to these five proteins inhibited
      binding of GBS type V to ME-180 cells by > or =85%. Recombinant undefined surface
      antigen (SAG1350), lipoprotein (SAG0971), and penicillin-binding protein 2b
      (SAG0765) each bound to ME-180 cells in a dose-dependent fashion, confirming
      their ability to act as ligands. Collectively, these data increase the number of
      potential GBS adherence factors and also suggest a role for these surface
      associated proteins in initial pathogenic events.

PMID- 17210665
TI  - Interleukin-12 promotes gamma interferon-dependent neutrophil recruitment in the
      lung and improves protection against respiratory Streptococcus pneumoniae
      infection.
AB  - The ability of exogenous interleukin-12 (IL-12) to elicit protective innate
      immune responses against the extracellular pathogen Streptococcus pneumoniae was
      tested by infecting BALB/c mice intranasally (i.n.) with S. pneumoniae after i.n.
      administration of IL-12. It was found that administration of IL-12 resulted in
      lower bacterial burdens in the infected mice and significantly improved survival
      rates. All IL-12-treated mice contained higher levels of pulmonary gamma
      interferon (IFN-gamma) after infection and significantly more neutrophils than
      infected mice not treated with IL-12. IFN-gamma was found to be essential for IL
      12-induced resistance and for neutrophil influx into the lungs, and the observed
      changes correlated with increased levels of the IL-8 homologue keratinocyte
      derived chemokine (KC). In addition, in vitro tumor necrosis factor alpha (TNF
      alpha) production by alveolar macrophages stimulated with heat-killed pneumococci
      was enhanced by IFN-gamma, and TNF-alpha in turn could enhance production of KC
      by lung cells. Finally, IL-12-induced protection was dependent upon the presence
      of neutrophils and the KC receptor CXCR2. Taken together, the results indicate
      that exogenous IL-12 can improve innate defense in the lung against S. pneumoniae
      by inducing IFN-gamma production, which in turn enhances chemokine expression,
      and promotes pulmonary neutrophil recruitment into the infected lung. The
      findings show that IL-12 and IFN-gamma can mediate a protective effect against
      respiratory infection caused by extracellular bacterial pathogens.

PMID- 17210666
TI  - Both epsilon-toxin and beta-toxin are important for the lethal properties of
      Clostridium perfringens type B isolates in the mouse intravenous injection model.
AB  - Clostridium perfringens is capable of producing up to 15 toxins, including alpha
      toxin (CPA), beta-toxin (CPB), epsilon-toxin (ETX), enterotoxin, beta2-toxin
      (CPB2), and perfringolysin O. Type B isolates, which must produce CPA, CPB, and
      ETX, are associated with animal illnesses characterized by sudden death or acute
      neurological signs, with or without intestinal damage. Type B pathogenesis in
      ruminants is poorly understood, with some animals showing lesions and clinical
      signs similar to those caused by either type C or type D infections. It is
      unknown whether host or environmental conditions are dominant for determining the
      outcome of type B disease or if disease outcomes are determined by variable
      characteristics of type B isolates. To help clarify this issue, 19 type B
      isolates were evaluated for toxin production during late-log-phase growth via
      quantitative Western blotting and by biological activity assays. Most type B
      isolates produced CPB levels similar to those produced by type C isolates in
      vitro and have the potential to produce genotype C-like disease. The lethality of
      type B isolate supernatants administered intravenously to mice was evaluated with
      or without prior trypsin treatment, and monoclonal antibody neutralization
      studies also were performed. Correlation analyses comparing toxin levels in type
      B supernatants versus lethality and neutralization studies both found that the
      main contributor to lethality without pretreatment with trypsin was CPB, whereas
      neutralization studies indicated that CPB and ETX were both important after
      trypsin pretreatment. At least part of the CPB produced by type B isolates
      remained active after trypsin treatment. However, the overall lethalities of most
      supernatants were lower after trypsin pretreatment. Also, there was a significant
      association between ETX, CPB2, and CPA production in vitro among type B isolates.
      However, our results suggest that both CPB and ETX are likely the most important
      contributors to the pathogenesis of C. perfringens type B infections in domestic
      animals.

PMID- 17210667
TI  - Resistance of Francisella tularensis strains against reactive nitrogen and oxygen
      species with special reference to the role of KatG.
AB  - Francisella tularensis is a facultative intracellular bacterial pathogen capable
      of proliferating within host macrophages. The mechanisms that explain the
      differences in virulence between various strains of the species are not well
      characterized. In the present study, we show that both attenuated (strain LVS)
      and virulent (strains FSC200 and SCHU S4) strains of the pathogen replicate at
      similar rates in resting murine peritoneal exudate cells (PEC). However, when PEC
      were activated by exposure to gamma interferon (IFN-gamma), they killed LVS more
      rapidly than virulent strains of the pathogen. Addition of N(G)-monomethyl-l
      arginine, an inhibitor of inducible nitric oxide synthase, to IFN-gamma-treated
      PEC, completely inhibited killing of the virulent strains, whereas it only
      partially blocked the killing of LVS. Similarly, in a cell-free system, SCHU S4
      and FSC200 were more resistant to killing by H(2)O(2) and ONOO(-) than F.
      tularensis LVS. Catalase encoded by katG is a bacterial factor that can detoxify
      bactericidal compounds such as H(2)O(2) and ONOO(-). To investigate its
      contribution to the virulence of F. tularensis, katG deletion-containing mutants
      of SCHU S4 and LVS were generated. Both mutants demonstrated enhanced
      susceptibility to H(2)O(2) in vitro but replicated as effectively as the parental
      strains in unstimulated PEC. In mice, LVS-DeltakatG was significantly attenuated
      compared to LVS whereas SCHU S4-DeltakatG, despite slower replication, killed
      mice as quickly as SCHU S4. This implies that clinical strains of the pathogen
      have katG-independent mechanisms to combat the antimicrobial effects exerted by
      H(2)O(2) and ONOO(-), the loss of which could have contributed to the attenuation
      of LVS.

PMID- 17210669
TI  - The effect of genetic background on the function of Saccharomyces cerevisiae mlh1
      alleles that correspond to HNPCC missense mutations.
AB  - Germline mutations in the DNA mismatch repair (MMR) gene MLH1 are associated with
      a large percentage of hereditary non-polyposis colorectal cancers. There are
      approximately 250 known human mutations in MLH1. Of these, one-third are missense
      variants that are often difficult to characterize with regards to pathogenicity.
      We analysed 28 alleles of baker's yeast MLH1 that correspond to non-truncating
      human mutant alleles listed in online HNPCC databases, 13 of which had not been
      previously studied in functional assays. Using the highly sensitive lys2::InsE
      A(14) reversion rate assay, we determined the MMR proficiency conferred by each
      allele in the S288c strain of Saccharomyces cerevisiae. Seven alleles conferred a
      null phenotype for MMR and eight others showed significant MMR defects,
      suggesting that all 15 are likely to be pathogenic in humans. In addition, we
      observed a strong correlation between these results, limited results from
      previous functional assays and clinical data. To test whether the potential
      pathogenicity of certain alleles depends on the genetic background of the host,
      we examined the mutation rates conferred by the mlh1 alleles in a second yeast
      strain, SK1, which is approximately 0.7% divergent from S288c. Many alleles
      displayed a difference in MMR efficiency between strain backgrounds with
      decreasing differences as the severity of the MMR defect increased. These
      findings suggest that genetic background can play an important role in
      determining the pathogenicity of MMR alleles and may explain cases of atypical
      colorectal cancer inheritance.

PMID- 17210668
TI  - Protection against cryptococcosis by using a murine gamma interferon-producing
      Cryptococcus neoformans strain.
AB  - We evaluated cell-mediated immune (CMI) responses in mice given a pulmonary
      infection with a Cryptococcus neoformans strain engineered to produce the Th1
      type cytokine gamma interferon (IFN-gamma). Mice given a pulmonary infection with
      an IFN-gamma-producing C. neoformans strain were able to resolve the primary
      infection and demonstrated complete (100%) protection against a second pulmonary
      challenge with a pathogenic C. neoformans strain. Pulmonary cytokine analyses
      showed that Th1-type/proinflammatory cytokine and chemokine expression were
      significantly higher and Th2-type cytokine expression was significantly lower in
      mice infected with the IFN-gamma-producing C. neoformans strain compared to wild
      type-infected mice. This increased pulmonary Th1-type cytokine expression was
      also associated with significantly lower pulmonary fungal burden and
      significantly higher pulmonary leukocyte and T-lymphocyte recruitment in mice
      infected with the IFN-gamma-producing C. neoformans strain compared to wild-type
      infected mice. Our results demonstrate that pulmonary infection of mice with a C.
      neoformans strain expressing IFN-gamma results in the stimulation of local Th1
      type anti-cryptococcal CMI responses and the development of protective host
      immunity against future pulmonary cryptococcal infections. The use of fungi
      engineered to produce host cytokines is a novel method to study immune responses
      to infection and may be useful in developing vaccine strategies in humans.

PMID- 17210670
TI  - A CTCF-binding silencer regulates the imprinted genes AWT1 and WT1-AS and
      exhibits sequential epigenetic defects during Wilms' tumourigenesis.
AB  - We have shown previously that AWT1 and WT1-AS are functionally imprinted in human
      kidney. In the adult kidney, expression of both transcripts is restricted to the
      paternal allele, with the silent maternal allele retaining methylation at the WT1
      antisense regulatory region (WT1 ARR). Here, we report characterization of the
      WT1 ARR differentially methylated region and show that it contains a
      transcriptional silencer element acting on both the AWT1 and WT1-AS promoters.
      DNA methylation of the silencer results in increased transcriptional repression,
      and the silencer is also shown to be an in vitro and in vivo target site for the
      imprinting regulator protein CTCF. Binding of CTCF is methylation-sensitive and
      limited to the unmethylated silencer. Potentiation of the silencer activity is
      demonstrated after CTCF protein is knocked down, suggesting a novel silencer
      blocking activity for CTCF. We also report assessment of WT1 ARR methylation in
      developmental and tumour tissues, including the first analysis of Wilms' tumour
      precursor lesions, nephrogenic rests. Nephrogenic rests show increases in
      methylation levels relative to foetal kidney and reductions relative to the adult
      kidney, together with biallelic expression of AWT1 and WT1-AS. Notably, the
      methylation status of CpG residues within the CTCF target site appears to
      distinguish monoallelic and biallelic expression states. Our data suggest that
      failure of methylation spreading at the WT1 ARR early in renal development,
      followed by imprint erasure, occurs during Wilms' tumourigenesis. We propose a
      model wherein imprinting defects at chromosome 11p13 may contribute to Wilms'
      tumourigenesis.

PMID- 17210671
TI  - Increased longevity and refractoriness to Ca(2+)-dependent neurodegeneration in
      Surf1 knockout mice.
AB  - Leigh syndrome associated with cytochrome c oxidase (COX) deficiency is a
      mitochondrial disorder usually caused by mutations of SURF1, a gene encoding a
      putative COX assembly factor. We present here a Surf1-/- recombinant mouse
      obtained by inserting a loxP sequence in the open reading frame of the gene. The
      frequency of -/-, +/+ and +/- genotypes in newborn mice followed a mendelian
      distribution, indicating that the ablation of Surf1 is compatible with postnatal
      survival. The biochemical and assembly COX defect was present in Surf1(loxP)-/-
      mice, but milder than in humans. Surprisingly, not only these animals failed to
      show spontaneous neurodegeneration at any age, but they also displayed markedly
      prolonged lifespan, and complete protection from Ca(2+)-dependent neurotoxicity
      induced by kainic acid. Experiments on primary neuronal cultures showed markedly
      reduced rise of cytosolic and mitochondrial Ca(2+) in Surf1(loxP)-/- neurons, and
      reduced mortality, compared to controls. The mitochondrial membrane potential was
      unchanged in KO versus wild-type neurons, suggesting that the effects of the
      ablation of Surf1 on Ca(2+) homeostasis, and possibly on longevity, may be
      independent, at least in part, from those on COX assembly and mitochondrial
      bioenergetics.

PMID- 17210672
TI  - Genome-wide oligonucleotide-based array comparative genome hybridization analysis
      of non-isolated congenital diaphragmatic hernia.
AB  - Non-isolated congenital diaphragmatic hernia (CDH+) is a severe birth defect that
      is often caused by de novo chromosomal anomalies. In this report, we use genome
      wide oligonucleotide-based array comparative genome hybridization (aCGH) followed
      by rapid real-time quantitative PCR analysis to identify, confirm and map
      chromosomal anomalies in a cohort of 26 CDH+ patients. One hundred and five
      putative copy number changes were identified by aCGH in our cohort of CDH+
      patients. Sixty-one of these changes (58%) had been previously described in
      normal controls. Twenty of the remaining 44 changes (45%) were confirmed by
      quantitative real-time PCR or standard cytogenetic techniques. These changes
      included de novo chromosomal abnormalities in five of the 26 patients (19%), two
      of whom had previously normal G-banded chromosome analyses. Data from these
      patients provide evidence for the existence of CDH-related genes on chromosomes
      2q37, 6p22-25 and 14q, and refine the CDH minimal deleted region on 15q26 to an
      interval that contains COUP-TFII and only eight other known genes. Although COUP
      TFII is likely to play a role in the development of CDH in patients with 15q26
      deletions, we did not find COUP-TFII mutations in 73 CDH samples. We conclude
      that the combination of oligonucleotide-based aCGH and quantitative real-time PCR
      is an effective method of identifying, confirming and mapping clinically relevant
      copy number changes in patients with CDH+. This method is more sensitive than G
      banded chromosome analysis and may find wide application in screening patients
      with congenital anomalies.

PMID- 17210673
TI  - Novel pycnodysostosis mouse model uncovers cathepsin K function as a potential
      regulator of osteoclast apoptosis and senescence.
AB  - Pycnodysostosis is a genetic bone disease featuring the unique bone homeostasis
      disorders of osteolysis and osteopetrosis in the same organism. The
      pathomechanism for pycnodysostosis has been largely unknown due to the
      unavailability of a pycnodysostosis mouse model with all the traits of the
      disease. We generated cathepsin K(-/-) mouse strains in the 129/Sv and C57BL/6J
      backgrounds and found that, only in the 129/Sv background, cathepsin K(-/-) mice
      exhibit many characteristics of the human pycnodysostosis-like phenotype. Our
      data indicated that 129/Sv cathepsin K(-/-) osteoclasts (OCs) lacked normal
      apoptosis and senescence and exhibited over-growth both in vitro and in vivo.
      These abnormalities resulted in an unusually high OC number, which is consistent
      with a recent case study of human pycnodysostosis. Our results show that
      cathepsin K function has different effects around the skeleton due to site
      specific variations in bone homeostasis, such as phenotypes of osteopetrosis in
      tibiae and osteolysis in calvariae as a result of cathepsin K mutation. Our data
      demonstrated that the expression levels of p19, p53 and p21 were significantly
      reduced in 129/Sv cathepsin K(-/-) OCs and forced expression of cathepsin K in
      pre-OCs induced premature senescence and increased expression of p19, p53 and
      p21. This is the first evidence that cathepsin K plays a key role in OC apoptosis
      and senescence, revealing the importance of OC senescence in bone homeostasis.
      The finding of this novel cathepsin K function provides insight into the
      pathomechanism of pycnodysostosis and may provide new drug targets for diseases
      involved in OC-related abnormal bone homeostasis.

PMID- 17210675
TI  - Regulation of mTOR by phosphatidic acid?
AB  - Interest in the regulation of the mammalian target of rapamycin (mTOR) has
      increased substantially in recent years largely because of an apparent link
      between mTOR and survival signals in human cancer cells. Much has been learned
      about the regulation of mTOR in response to survival signals generated by
      phosphatidylinositol 3-kinase (PI3K). However, another mechanism for regulating
      mTOR has been proposed involving the generation of phosphatidic acid (PA). PA is
      the metabolic product of phospholipase D (PLD), whose activity is elevated in a
      large number of human cancers, and, like PI3K, has been implicated in the
      survival of human cancer cells. Although the regulation of mTOR by the PI3K
      signaling pathway is well established, a role for PLD and PA in regulating mTOR
      has been controversial. In this review, the evidence implicating PLD and PA in
      the regulation of mTOR is summarized, and the implications of this novel and
      potentially important mechanism for regulating mTOR are discussed.

PMID- 17210674
TI  - Functional characterization of GATA3 mutations causing the hypoparathyroidism
      deafness-renal (HDR) dysplasia syndrome: insight into mechanisms of DNA binding
      by the GATA3 transcription factor.
AB  - The hypoparathyroidism-deafness-renal (HDR) dysplasia syndrome is an autosomal
      dominant disorder caused by mutations of the dual zinc finger transcription
      factor, GATA3. We investigated 21 HDR probands and 14 patients with isolated
      hypoparathyroidism for GATA3 abnormalities. Thirteen different heterozygous
      germline mutations were identified in patients with HDR. These consisted of three
      nonsense mutations, six frameshifting deletions, two frameshifting insertions,
      one missense (Leu348Arg) mutation and one acceptor splice site mutation. The
      splice site mutation was demonstrated to cause a pre-mRNA processing abnormality
      leading to the use of an alternative acceptor site 8 bp downstream of the normal
      site, resulting in a frameshift and prematurely terminated protein.
      Electrophoretic mobility shift assays (EMSAs) revealed three classes of GATA3
      mutations: those that lead to a loss of DNA binding which represent over 90% of
      all mutations, and involved a loss of the carboxy-terminal zinc finger; those
      that resulted in a reduced DNA-binding affinity; and those (e.g. Leu348Arg) that
      did not alter DNA binding or the affinity but likely altered the conformational
      change that occurs during binding in the DNA major groove as predicted by a three
      dimensional modeling. These results elucidate further the molecular mechanisms
      underlying the altered functions of mutants of this zinc finger transcription
      factor and their role in causing this developmental anomaly. No mutations were
      identified in patients with isolated hypoparathyroidism, thereby indicating that
      GATA3 abnormalities are more likely to result in two or more of the phenotypic
      features of the HDR syndrome and not in one, such as isolated hypoparathyroidism.

PMID- 17210676
TI  - Perspectives of gammadelta T cells in tumor immunology.
AB  - Subsets of human gammadelta T cells recognize tumor cell-expressed ligands that
      are not seen by the T-cell receptor of conventional alphabeta T cells. Vdelta1 T
      cells recognize MHC class I chain-related molecules A and B and UL-16-binding
      proteins expressed at variable levels on epithelial tumor cells and some
      leukemias and lymphomas. In addition, therapeutically used aminobisphosphonates
      and synthetic phosphoantigens activate Vdelta2 T cells, the dominant subset of
      gammadelta T cells in human peripheral blood that display strong cytotoxicity
      towards various epithelial tumors. Intentional activation of gammadelta T cells
      in vivo and/or adoptive cell therapy with in vitro expanded gammadelta T cells
      holds considerable promise as a novel immunotherapy in certain types of cancer.

PMID- 17210677
TI  - Extracellular matrix metalloproteinase inducer up-regulates the urokinase-type
      plasminogen activator system promoting tumor cell invasion.
AB  - Extracellular matrix metalloproteinase inducer (EMMPRIN) is a membrane
      glycoprotein overexpressed in many cancer tissues and is known for its ability to
      stimulate MMP expression. In this work, we show that EMMPRIN is also a regulator
      of the urokinase-type plasminogen activation (uPA) system of serine proteases,
      thus participating to the increase of the overall proteolytic function of the
      cancer cells. Enhanced EMMPRIN expression in a tumorigenic breast epithelial cell
      line NS2T2A increased the levels of uPA, uPA receptor, and the uPA inhibitor
      plasminogen activator inhibitor-1 (PAI-1), as measured by quantitative reverse
      transcription-PCR, Western blot, and plasminogen-casein zymography. This response
      was down-regulated by either EMMPRIN small interfering RNA or a blocking antibody
      to EMMPRIN. EMMPRIN-containing purified membrane fraction from Chinese hamster
      ovary cells when added exogenously to NS2T2A cells induced a similar activation
      of the uPA/PAI-1 system. Additionally, overexpression of EMMPRIN in NS2T2A cells
      increased uPA levels in cocultured endothelial cells, showing a paracrine
      regulation loop involving a tumor-stroma interaction. EMMPRIN-expressing cells
      also exhibited enhanced invasive potential in vitro, and the use of amiloride
      (uPA inhibitor) and marimastat (MMP inhibitor) showed that the two proteolytic
      systems reduced alone and in combination the invasive potential mediated through
      EMMPRIN. These data show a novel regulatory pathway for uPA activity and suggest
      that EMMPRIN is involved in uPA dysregulation observed in cancer.

PMID- 17210678
TI  - Ribonucleotide reductase small subunit p53R2 facilitates p21 induction of G1
      arrest under UV irradiation.
AB  - p53R2, which is one of the two known ribonucleotide reductase small subunits (the
      other being M2), is suggested to play an important role in supplying
      deoxynucleotide triphosphates (dNTP) for DNA repair during the G(1) or G(2) phase
      of the cell cycle. The ability of p53R2 to supply dNTPs for repairing DNA damages
      requires the presence of a functional p53 tumor suppressor. Here, we report in
      vivo physical interaction and colocalization of p53R2 and p21 before DNA damage.
      Mammalian two-hybrid assay further indicates that the amino acids 1 to 113 of
      p53R2 are critical for interacting with the NH(2)-terminal region (amino acids 1
      93) of p21. The binding between p21 and p53R2 decreases inside the nucleus in
      response to UV, the time point of which corresponds to the increased binding of
      p21 with cyclin-dependent kinase-2 (Cdk2), and the decreased Cdk2 activity in the
      nucleus at G(1). Interestingly, p53R2 dissociates from p21 but facilitates the
      accumulation of p21 in the nucleus in response to UV. On the other hand, the
      ribonucleotide reductase activity increases at the corresponding time in response
      to UV. These data suggest a new function of p53R2 of cooperating with p21 during
      DNA repair at G(1) arrest.

PMID- 17210679
TI  - Tumor-targeted enzyme/prodrug therapy mediates long-term disease-free survival of
      mice bearing disseminated neuroblastoma.
AB  - Neural stem cells and progenitor cells migrate selectively to tumor loci in vivo.
      We exploited the tumor-tropic properties of HB1.F3.C1 cells, an immortalized cell
      line derived from human fetal telencephalon, to deliver the cDNA encoding a
      secreted form of rabbit carboxylesterase (rCE) to disseminated neuroblastoma
      tumors in mice. This enzyme activates the prodrug CPT-11 more efficiently than do
      human enzymes. Mice bearing multiple tumors were treated with rCE-expressing
      HB1.F3.C1 cells and schedules of administration of CPT-11 that produced levels of
      active drug (SN-38) tolerated by patients. Both HB1.F3.C1 cells and CPT-11 were
      given i.v. None of the untreated mice and 30% of mice that received only CPT-11
      survived long term. In contrast, 90% of mice treated with rCE-expressing
      HB1.F3.C1 cells and 15 mg/kg CPT-11 survived for 1 year without detectable
      tumors. Plasma carboxylesterase activity and SN-38 levels in mice receiving both
      rCE-expressing HB1.F3.C1 cells (HB1.F3.C1/AdCMVrCE) and CPT-11 were comparable
      with those in mice receiving CPT-11 only. These data support the hypothesis that
      the antitumor effect of the described neural stem/progenitor cell-directed enzyme
      prodrug therapy (NDEPT) is mediated by production of high concentrations of
      active drug selectively at tumor sites, thereby maximizing the antitumor effect
      of CPT-11. NDEPT approaches merit further investigation as effective, targeted
      therapy for metastatic tumors. We propose that the described approach may have
      greatest use for eradicating minimum residual disease.

PMID- 17210680
TI  - Human monocytes, but not dendritic cells derived from them, are defective in base
      excision repair and hypersensitive to methylating agents.
AB  - Monocytes and dendritic cells are key players in the immune response. Because
      dendritic cells drive the tumor host defense, it is important that monocytes and
      dendritic cells survive cytotoxic tumor therapy. Although most of the anticancer
      drugs target DNA, the DNA repair capacity of monocytes and dendritic cells has
      not yet been investigated. We studied the sensitivity of monocytes and monocyte
      derived dendritic cells against various genotoxic agents and found monocytes to
      be more sensitive to overall cell kill and apoptosis upon exposure to methylating
      agents (e.g., N-methyl-N'-nitro-N-nitrosoguanidine, methyl methanesulfonate, and
      the anticancer drug temozolomide). On the other hand, upon treatment with the
      cross-linking chemotherapeutics fotemustine, mafosfamide, and cisplatin,
      monocytes and dendritic cells responded in the same way. Monocytes were also more
      sensitive than lymphocytes. The data indicate a defect in the repair of DNA
      methylation damage in monocytes. Because the expression of the repair protein
      O(6)-methylguanine-DNA methyltransferase was higher in monocytes than in
      dendritic cells, and because its inhibition by O(6)-benzylguanine had no effect
      on the sensitivity of monocytes, we investigated the base excision repair (BER)
      pathway. In contrast to dendritic cells, monocytes are unable to perform BER
      following exposure to methylating agents. Expression studies revealed that
      monocytes lack XRCC1 and ligase IIIalpha, whereas dendritic cells, similar to
      human lymphocytes, express these repair proteins at a high level. The data
      revealed a DNA repair defect in a specific human cell population. The BER defect
      in monocytes may cause them to be selectively killed during tumor therapy with
      alkylating agents, provoking hematotoxicity and sustained immunosuppression.

PMID- 17210681
TI  - Credentialing preclinical pediatric xenograft models using gene expression and
      tissue microarray analysis.
AB  - Human tumor xenografts have been used extensively for rapid screening of the
      efficacy of anticancer drugs for the past 35 years. The selection of appropriate
      xenograft models for drug testing has been largely empirical and has not
      incorporated a similarity to the tumor type of origin at the molecular level.
      This study is the first comprehensive analysis of the transcriptome of a large
      set of pediatric xenografts, which are currently used for preclinical drug
      testing. Suitable models representing the tumor type of origin were identified.
      It was found that the characteristic expression patterns of the primary tumors
      were maintained in the corresponding xenografts for the majority of samples.
      Because a prerequisite for developing rationally designed drugs is that the
      target is expressed at the protein level, we developed tissue arrays from these
      xenografts and corroborated that high mRNA levels yielded high protein levels for
      two tested genes. The web database and availability of tissue arrays will allow
      for the rapid confirmation of the expression of potential targets at both the
      mRNA and the protein level for molecularly targeted agents. The database will
      facilitate the identification of tumor markers predictive of response to tested
      agents as well as the discovery of new molecular targets.

PMID- 17210682
TI  - Gene expression profiling reveals a massive, aneuploidy-dependent transcriptional
      deregulation and distinct differences between lymph node-negative and lymph node
      positive colon carcinomas.
AB  - To characterize patterns of global transcriptional deregulation in primary colon
      carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale
      Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide
      microarrays. For 30 of the tumors, expression profiles were compared with those
      from matched normal mucosa samples. We identified a set of 1,950 genes with
      highly significant deregulation between tumors and mucosa samples (P < 1e-7). A
      significant proportion of these genes mapped to chromosome 20 (P = 0.01).
      Seventeen genes had a >5-fold average expression difference between normal colon
      mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative
      oncogene. Furthermore, we identified 68 genes that were significantly
      differentially expressed between lymph node-negative and lymph node-positive
      tumors (P < 0.001), the functional annotation of which revealed a preponderance
      of genes that play a role in cellular immune response and surveillance. The
      microarray-derived gene expression levels of 20 deregulated genes were validated
      using quantitative real-time reverse transcription-PCR in >40 tumor and normal
      mucosa samples with good concordance between the techniques. Finally, we
      established a relationship between specific genomic imbalances, which were mapped
      for 32 of the analyzed colon tumors by comparative genomic hybridization, and
      alterations of global transcriptional activity. Previously, we had conducted a
      similar analysis of primary rectal carcinomas. The systematic comparison of colon
      and rectal carcinomas revealed a significant overlap of genomic imbalances and
      transcriptional deregulation, including activation of the Wnt/beta-catenin
      signaling cascade, suggesting similar pathogenic pathways.

PMID- 17210683
TI  - Role for amplification and expression of glypican-5 in rhabdomyosarcoma.
AB  - Overexpression of genes, through genomic amplification and other mechanisms, can
      critically affect the behavior of tumor cells. Genomic amplification of the 13q31
      32 region is reported in many tumors, including rhabdomyosarcomas that are
      primarily pediatric sarcomas resembling developing skeletal muscle. The minimum
      overlapping region of amplification at 13q31-32 in rhabdomyosarcomas was defined
      as containing two genes: Glypican-5 (GPC5) encoding a cell surface proteoglycan
      and C13orf25 encompassing the miR-17-92 micro-RNA cluster. Genomic copy number
      and gene expression analyses of rhabdomyosarcomas indicated that GPC5 was the
      only gene consistently expressed and up-regulated in all cases with
      amplification. Constitutive overexpression and knockdown of GPC5 expression in
      rhabdomyosarcoma cell lines increased and decreased cell proliferation,
      respectively. A correlation between expression levels of nascent pre-rRNA and
      GPC5 (P = 0.001), but not a C13orf25 transcript containing miR-17-92, in primary
      samples supports an association of GPC5 with proliferative capacity in vivo. We
      show that GPC5 increases proliferation through potentiating the action of the
      growth factors fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF),
      and Wnt1A. GPC5 enhanced the intracellular signaling of FGF2 and HGF and altered
      the cellular distribution of FGF2. The mesoderm-inducing effect of FGF2 and FGF4
      in Xenopus blastocysts was also enhanced. Our data are consistent with a role of
      GPC5, in the context of sarcomagenesis, in enhancing FGF signaling that leads to
      mesodermal cell proliferation without induction of myogenic differentiation.
      Furthermore, the properties of GPC5 make it an attractive target for therapeutic
      intervention in rhabdomyosarcomas and other tumors that amplify and/or
      overexpress the gene.

PMID- 17210684
TI  - Daxx cooperates with the Axin/HIPK2/p53 complex to induce cell death.
AB  - Daxx, a death domain-associated protein, has been implicated in proapoptosis,
      antiapoptosis, and transcriptional regulation. Many factors known to play
      critically important roles in controlling apoptosis and gene transcription have
      been shown to associate with Daxx, including the Ser/Thr protein kinase HIPK2,
      promyelocytic leukemia protein, histone deacetylases, and the chromatin
      remodeling protein ATRX. Although it is clear that Daxx may exert multiple
      functions, the underlying mechanisms remain far from clear. Here, we show that
      Axin, originally identified for its scaffolding role to control beta-catenin
      levels in Wnt signaling, strongly associates with Daxx at endogenous levels. The
      Daxx/Axin complex formation is enhanced by UV irradiation. Axin tethers Daxx to
      the tumor suppressor p53, and cooperates with Daxx, but not DaxxDeltaAxin, which
      is unable to interact with Axin, to stimulate HIPK2-mediated Ser(46)
      phosphorylation and transcriptional activity of p53. Interestingly, Axin and Daxx
      seem to selectively activate p53 target genes, with strong activation of PUMA,
      but not p21 or Bax. Daxx-stimulated p53 transcriptional activity was
      significantly diminished by small interfering RNA against Axin; Daxx fails to
      inhibit colony formation in Axin(-/-) cells. Moreover, UV-induced cell death was
      attenuated by the knockdown of Axin and Daxx. All these results show that Daxx
      cooperates with Axin to stimulate p53, and implicate a direct role for Axin,
      HIPK2, and p53 in the proapoptotic function of Daxx. We have hence unraveled a
      novel aspect of p53 activation and shed new light on the ultimate understanding
      of the Daxx protein, perhaps most pertinently, in relation to stress-induced cell
      death.

PMID- 17210685
TI  - Transcriptional cooperation between the transforming growth factor-beta and Wnt
      pathways in mammary and intestinal tumorigenesis.
AB  - Transforming growth factor-beta (TGF-beta) and Wnt ligands function in numerous
      developmental processes, and alterations of both signaling pathways are
      associated with common pathologic conditions, including cancer. To obtain insight
      into the extent of interdependence of the two signaling cascades in regulating
      biological responses, we used an oligonucleotide microarray approach to identify
      Wnt and TGF-beta target genes using normal murine mammary gland epithelial cells
      as a model. Combination treatment of TGF-beta and Wnt revealed a novel
      transcriptional program that could not have been predicted from single ligand
      treatments and included a cohort of genes that were cooperatively induced by both
      pathways. These included both novel and known components or modulators of TGF
      beta and Wnt pathways, suggesting that mutual feedback is a feature of the
      coordinated activities of the ligands. The majority of the cooperative targets
      display increased expression in tumors derived from either Min (many intestinal
      neoplasia) or mouse mammary tumor virus (MMTV)-Wnt1 mice, two models of Wnt
      induced tumors, with nine of these genes (Ankrd1, Ccnd1, Ctgf, Gpc1, Hs6st2,
      IL11, Inhba, Mmp14, and Robo1) showing increases in both. Reduction of TGF-beta
      signaling by expression of a dominant-negative TGF-beta type II receptor in
      bigenic MMTV-Wnt1/DNIIR mice increased mammary tumor latency and was correlated
      with a decrease in expression of Gpc1, Inhba, and Robo1, three of the TGF
      beta/Wnt cooperative targets. Our results indicate that the TGF-beta and Wnt/beta
      catenin pathways are firmly intertwined and generate a unique gene expression
      pattern that can contribute to tumor progression.

PMID- 17210686
TI  - Induction of human arylamine N-acetyltransferase type I by androgens in human
      prostate cancer cells.
AB  - Human arylamine N-acetyltransferases (NAT) bioactivate arylamine and heterocyclic
      amine carcinogens present in red meat and tobacco products. As a result, factors
      that regulate expression of NATs have the potential to modulate cancer risk in
      individuals exposed to these classes of carcinogens. Because epidemiologic
      studies have implicated well-done meat consumption as a risk factor for prostate
      cancer, we have investigated the effects of androgens on the expression of
      arylamine N-acetyltransferase type I (NAT1). We show that NAT1 activity is
      induced by R1881 in androgen receptor (AR)-positive prostate lines 22Rv1 and
      LNCaP, but not in the AR-negative PC-3, HK-293, or HeLa cells. The effect of
      R1881 was dose dependent, with an EC(50) for R1881 of 1.6 nmol/L. Androgen up
      regulation of NAT1 was prevented by the AR antagonist flutamide. Real-time PCR
      showed a significant increase in NAT1 mRNA levels for R1881-treated cells (6.60
      +/- 0.80) compared with vehicle-treated controls (1.53 +/- 0.17), which was not
      due to a change in mRNA stability. The increase in NAT1 mRNA was attenuated by
      concurrent cycloheximide treatment, suggesting that the effect of R1881 may not
      be by direct transcriptional activation of NAT1. The dominant NAT1 transcript
      present following androgen treatment was type IIA, indicating transcriptional
      activation from the major NAT1 promoter P1. A series of luciferase reporter
      deletions mapped the androgen responsive motifs to a 157-bp region of P1 located
      745 bases upstream of the first exon. These results show that human NAT1 is
      induced by androgens, which may have implications for cancer risk in individuals.

PMID- 17210688
TI  - Bin1 ablation in mammary gland delays tissue remodeling and drives cancer
      progression.
AB  - Genes that modify oncogenesis may influence dormancy versus progression in
      cancer, thereby affecting clinical outcomes. The Bin1 gene encodes a
      nucleocytosolic adapter protein that interacts with and suppresses the cell
      transforming activity of Myc. Bin1 is often attenuated in breast cancer but its
      ability to negatively modify oncogenesis or progression in this context has not
      been gauged directly. In this study, we investigated the effects of mammary gland
      specific deletion of Bin1 on initiation and progression of breast cancer in mice.
      Bin1 loss delayed the outgrowth and involution of the glandular ductal network
      during pregnancy but had no effect on tumor susceptibility. In contrast, in mice
      where tumors were initiated by the ras-activating carcinogen 7,12
      dimethylbenz(a)anthracene, Bin1 loss strongly accentuated the formation of poorly
      differentiated tumors characterized by increased proliferation, survival, and
      motility. This effect was specific as Bin1 loss did not accentuate progression of
      tumors initiated by an overexpressed mouse mammary tumor virus-c-myc transgene,
      which on its own produced poorly differentiated and aggressive tumors. These
      findings suggest that Bin1 loss cooperates with ras activation to drive
      progression, establishing a role for Bin1 as a negative modifier of oncogenicity
      and progression in breast cancer.

PMID- 17210687
TI  - Identification of a novel tumor suppressor gene p34 on human chromosome 6q25.1.
AB  - In this study, we observed loss of heterozygosity (LOH) in human chromosomal
      fragment 6q25.1 in sporadic lung cancer patients. LOH was observed in 65% of the
      26 lung tumors examined and was narrowed down to a 2.2-Mb region. Single
      nucleotide polymorphism (SNP) analysis of genes located within this region
      identified a candidate gene, termed p34. This gene, also designated as ZC3H12D,
      C6orf95, FLJ46041, or dJ281H8.1, carries an A/G nonsynonymous SNP at codon 106,
      which alters the amino acid from lysine to arginine. Nearly 73% of heterozygous
      lung cancer tissues with LOH and the A/G SNP also exhibited loss of the A allele.
      In vitro clonogenic and in vivo nude mouse studies showed that overexpression of
      the A allele exerts tumor suppressor function compared with the G allele. p34 is
      located within a recently mapped human lung cancer susceptibility locus, and
      association of the p34 A/G SNP was tested among these families. No significant
      association between the less frequent G allele and lung cancer susceptibility was
      found. Our results suggest that p34 may be a novel tumor suppressor gene involved
      in sporadic lung cancer but it seems not to be the candidate familial lung cancer
      susceptibility gene linked to chromosomal region 6q23-25.

PMID- 17210689
TI  - Dominant-negative Fas mutation is reversed by down-expression of c-FLIP.
AB  - Fas triggering by agonistic antibodies or by its cognate ligand, FasL, induces
      apoptotic cell death, whereas mutation in the Fas death domain is associated with
      lymphoma progression. On prolonged culture in the presence of an agonistic anti
      Fas antibody, we raised a Jurkat cell line resistant to agonistic antibodies but
      still sensitive to soluble FasL, which carried at the heterozygous state, a point
      mutation into the Fas death domain. Down-modulation of c-FLIP expression reversed
      the blockade of the Fas pathway. We show that the activation threshold for the
      Fas receptor is more easily overcome by multimeric FasL than by agonistic
      antibodies and that the increase of this threshold due to mutation in the Fas
      death domain can be overcome by acting on a downstream effector of the Fas
      signal, c-FLIP. These findings put forward a new approach to eradicate Fas
      resistant tumor cells.

PMID- 17210690
TI  - DNA replication licensing factor minichromosome maintenance deficient 5 rescues
      p53-mediated growth arrest.
AB  - Inactivation of p53 signaling by mutation of p53 itself or abrogation of its
      normal function by other transfactors, such as MDM2, is a key event in the
      development of most human cancers. To identify novel regulators of p53, we have
      used a phenotype-based selection in which a total cDNA library in a retroviral
      vector has been introduced into TR9-7ER cells, which arrest when p53 is expressed
      from a tetracycline-regulated promoter. We have isolated several clones derived
      from cells that are not growth-arrested when p53 is overexpressed. In one clone,
      the levels of p53, p21, and MDM2 are comparable with those in TR9-7ER cells and,
      therefore, the abrogation of growth arrest by an exogenous cDNA is likely to be
      distal to p21. Using reverse transcription-PCR, we were able to isolate a cDNA of
      approximately 2.2 kb, which was found to have 99% identity to the nucleotides
      between about 80 and 2,288 of the open reading frame of a gene encoding DNA
      replication licensing factor. It encodes complete peptide of 734 residues of this
      protein also called minichromosome maintenance deficient 5 (MCM5) or cell
      division cycle 46 (Saccharomyces cerevisiae). Northern and Western blot analyses
      revealed that the expression of MCM5 and its transcriptional regulator, E2F1, is
      negatively regulated by p53. When MCM5 cDNA was reintroduced into fresh TR9-7ER
      cells, numerous colonies that grow in the absence of tetracycline were formed.
      This novel observation establishes a role for MCM5 in negating the growth arrest
      function of p53.

PMID- 17210691
TI  - Tumor necrosis factor-alpha blocks apoptosis in melanoma cells when BRAF
      signaling is inhibited.
AB  - The protein kinase BRAF, a component of the RAS/RAF/mitogen-activated protein
      kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling
      pathway, regulates cell fate in response to extracellular signals. Activating
      mutations in BRAF occur in approximately 70% of human melanomas. The active
      proteins stimulate constitutive pathway signaling, proliferation, and survival.
      Thus, inhibition of BRAF signaling in melanoma cells causes cell cycle arrest and
      induces cell death through apoptosis, validating BRAF as an important therapeutic
      target. Here, we show that the apoptosis induced by inhibition of BRAF signaling
      in melanoma cells can be prevented if the cells are treated with tumor necrosis
      factor (TNF)-alpha. This allows the cells to recover from the inhibition of BRAF
      signaling and reenter the cell cycle. This effect occurs due to a specific TNF
      alpha and BRAF interaction because TNF-alpha does not prevent cell death in the
      presence of cisplatin, nitrogen mustard or thapsigargin. Furthermore, the
      cytokines Fas ligand, TNF-related apoptosis-inducing ligand, interleukin (IL)-1,
      and IL-6 do not prevent cell death when BRAF signaling is inhibited. The survival
      mechanism requires nuclear factor-kappaB (NF-kappaB) transcription factor
      activity, which is strongly induced by TNF-alpha in these cells. These findings
      suggest that drugs that target the BRAF/MEK pathway could be combined with agents
      that target TNF-alpha and/or NF-kappaB signaling to provide exciting new
      therapeutic opportunities for the treatment of melanoma.

PMID- 17210692
TI  - Aberrant splicing of cyclin-dependent kinase-associated protein phosphatase KAP
      increases proliferation and migration in glioblastoma.
AB  - The cyclin-dependent kinase (Cdk)-associated protein phosphatase KAP is a dual
      specificity phosphatase of which the only known function is to dephosphorylate
      Cdk2 and inhibit cell cycle progression. Paradoxically, we find increased KAP
      mRNA expression in malignant astrocytomas, which correlates with increasing
      histologic grade and decreased patient survival. We have resolved this apparent
      paradox with the discovery of aberrant KAP splicing in malignant astrocytomas
      that leads to increased expression of KAP-related transcripts but decreased KAP
      protein expression. In addition, the aberrant splicing generates a dominant
      negative KAP variant that increases proliferation. We provide the first evidence
      that KAP not only regulates proliferation but also inhibits migration by
      decreasing cdc2 mRNA and protein expression. The effect of KAP on cdc2 expression
      requires its phosphatase activity but does not involve direct dephosphorylation
      of cdc2. Thus, KAP regulates both cdc2-dependent migration and Cdk2-dependent
      proliferation, and its loss due to aberrant splicing increases malignancy in
      human gliomas.

PMID- 17210693
TI  - Gene expression profile of metastatic human pancreatic cancer cells depends on
      the organ microenvironment.
AB  - To determine the influence of the microenvironment on changes in gene expression,
      we did microarray analysis on three variant lines of a human pancreatic cancer
      (FG, L3.3, and L3.6pl) with different metastatic potentials. The variant lines
      were grown in tissue culture in the subcutis (ectopic) or pancreas (orthotopic)
      of nude mice. Compared with tissue culture, the number of genes of which the
      expression was affected by the microenvironment was up-regulated in tumors
      growing in the subcutis and pancreas. In addition, highly metastatic L3.6pl cells
      growing in the pancreas expressed significantly higher levels of 226 genes than
      did the L3.3 or FG variant cells. Growth of the variant lines in the subcutis did
      not yield similar results, indicating that the orthotopic microenvironment
      significantly influences gene expression in pancreatic cancer cells. These data
      suggest that investigations of the functional consequence of gene expression
      require accounting for experimental growth conditions.

PMID- 17210694
TI  - A glycolytic mechanism regulating an angiogenic switch in prostate cancer.
AB  - The generation of an "angiogenic switch" is essential for tumor growth, yet its
      regulation is poorly understood. In this investigation, we explored the linkage
      between metastasis and angiogenesis through CXCL12/CXCR4 signaling. We found that
      CXCR4 regulates the expression and secretion of the glycolytic enzyme
      phosphoglycerate kinase 1 (PGK1). Overexpression of PGK1 reduced the secretion of
      vascular endothelial growth factor and interleukin-8 and increased the generation
      of angiostatin. At metastatic sites, however, high levels of CXCL12 signaling
      through CXCR4 reduced PGK1 expression, releasing the angiogenic response for
      metastastic growth. These data suggest that PGK1 is a critical downstream target
      of the chemokine axis and an important regulator of an "angiogenic switch" that
      is essential for tumor and metastatic growth.

PMID- 17210695
TI  - Heterozygous deletion of mitotic arrest-deficient protein 1 (MAD1) increases the
      incidence of tumors in mice.
AB  - Mitotic arrest-deficient protein 1 (MAD1) is a component of the mitotic spindle
      assembly checkpoint. We have created a knockout mouse model to examine the
      physiologic consequence of reduced MAD1 function. Mad1(+/-) mice were
      successfully generated, but repeated paired mating of Mad1(+/-) with Mad1(+/-)
      mice failed to produce a single Mad1(-/-) animal, suggesting that the latter
      genotype is embryonic lethal. In aging studies conducted for >18 months, Mad1(+/
      ) mice compared with control wild-type (wt) littermates showed a 2-fold higher
      incidence of constitutive tumors. Moreover, 42% of Mad1(+/-) (P < 0.03), but 0%
      of wt, mice developed neoplasia after treatment with vincristine, a microtubule
      depolymerization agent. Mad1(+/-) mouse embryonic fibroblasts (MEF) were found to
      be more prone than wt cells to become aneuploid; Mad1(+/-), but not wt, MEFs
      produced fibrosarcomas when explanted into nude mice. Our results indicate an
      essential MAD1 function in mouse development and correlate Mad1
      haploinsufficiency with increased constitutive tumors.

PMID- 17210697
TI  - c-Jun NH2-terminal kinase 2 is required for Ras transformation independently of
      activator protein 1.
AB  - Active Ras oncogene is expressed in approximately 30% of human cancers. Yet, very
      little is known about the molecular mechanisms responsible for its transforming
      potential. Here, we show that H-Ras-mediated transformation requires isoform 2 of
      the c-Jun-NH(2)-terminal kinase (JNK). H-Ras-transduced JNK2-deficient (Jnk2-/-)
      murine embryonic fibroblasts (MEFs) were severely inhibited in colony formation
      and growth in soft agar in vitro as well as in tumor formation in immunodeficient
      mice as compared with corresponding Jnk1-/- and wild-type MEFs. Accordingly, the
      RNA interference-based depletion of JNK2 form wild-type MEFs also resulted in
      defective Ras transformation. The extra barrier against H-Ras transformation in
      Jnk2-/- MEFs was not due to their inability to inactivate p53 signaling because
      all JNK2-deficient MEF lines had lost p19(Arf). Furthermore, expression of the E6
      protein of the human papilloma virus failed to overcome the transformation
      defect. It could, however, be overcome by coexpression of H-Ras with the SV40
      large T antigen or c-Myc. Surprisingly, the H-Ras-transduced JNK2-deficient MEFs
      exhibited higher activity of activator protein-1 and higher levels of c-Jun
      expression compared with H-Ras-transduced JNK1-deficient or wild-type cells,
      indicating that the key target of JNK2 during Ras transformation was divergent
      from activator protein-1. These results clearly show that a single kinase, JNK2,
      could control Ras transformation and thus point out a vulnerable control point
      that may prove important for the tumor development in general.

PMID- 17210696
TI  - Akt1 ablation inhibits, whereas Akt2 ablation accelerates, the development of
      mammary adenocarcinomas in mouse mammary tumor virus (MMTV)-ErbB2/neu and MMTV
      polyoma middle T transgenic mice.
AB  - Ample evidence to date links the phosphatidylinositol 3-kinase-regulated protein
      kinase Akt with the induction and progression of human cancer, including breast
      cancer. However, there are three Akt isoforms with limited information about
      their specificity during oncogenesis. This study addresses the role of the three
      isoforms in polyoma middle T (PyMT) and ErbB2/Neu-driven mammary adenocarcinomas
      in mice. The effects of ablation of Akt1, Akt2, and Akt3 on the induction and the
      biology of these tumors were dramatically different, with ablation of Akt1
      inhibiting, ablation of Akt2 accelerating, and ablation of Akt3 having a small,
      not statistically significant, inhibitory effect on tumor induction by both
      transgenes. Whereas PyMT-induced tumors are all invasive, Akt1(-/-)Neu-induced
      tumors are more invasive than Akt2(-/-)Neu-induced tumors. Invasiveness, however,
      does not always correlate with metastasis. Ablation of individual Akt isoforms
      does not affect the development of the mammary gland during puberty or the
      expression of the transgenes. Akt ablation, therefore, influences tumor induction
      by modulating transgene-induced oncogenic signaling. Immunostaining for Ki-67 and
      cyclin D1 and terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling assays on tissue sections revealed that the delay of tumor induction in
      Akt1 knockout mice is due to the inhibitory effects of Akt1 ablation on cell
      proliferation and survival. Given that these animal models exhibit significant
      similarities to human breast cancer, the results of the present study may have
      significant translational implications because they may influence how Akt
      inhibitors will be used in the treatment of human cancer.

PMID- 17210699
TI  - hTERT is expressed in cancer cell lines despite promoter DNA methylation by
      preservation of unmethylated DNA and active chromatin around the transcription
      start site.
AB  - hTERT, which encodes the catalytic subunit of telomerase and is expressed in most
      immortalized and cancer cells, has been reported to have increased DNA
      methylation in its promoter region in many cancers. This pattern is inconsistent
      with observations that DNA methylation of promoter CpG islands is typically
      associated with gene silencing. Here, we provide a comprehensive analysis of
      promoter DNA methylation, chromatin patterns, and expression of hTERT in cancer
      and immortalized cells. Methylation-specific PCR and bisulfite sequencing of the
      hTERT promoter in breast, lung, and colon cancer cells show that all cancer cell
      lines retain alleles with little or no methylation around the transcription start
      site despite being densely methylated in a region 600 bp upstream of the
      transcription start site. By real-time reverse transcription-PCR, all cancer cell
      lines express hTERT. Chromatin immunoprecipitation (ChIP) analysis reveals that
      both active (acetyl-H3K9 and dimethyl-H3K4) and inactive (trimethyl-H3K9 and
      trimethyl-H3K27) chromatin marks are present across the hTERT promoter. However,
      using a novel approach combining methylation analysis of ChIP DNA, we show that
      active chromatin marks are associated with unmethylated DNA, whereas inactive
      marks of chromatin are associated with methylated DNA in the region around the
      transcription start site. These results show that DNA methylation patterns of the
      hTERT promoter (-150 to +150 around the transcription start) are consistent with
      the usual dynamics of gene expression in that the absence of methylation in this
      region and the association with active chromatin marks allow for the continued
      expression of hTERT.

PMID- 17210698
TI  - Amplification of tumor hypoxic responses by macrophage migration inhibitory
      factor-dependent hypoxia-inducible factor stabilization.
AB  - Low oxygen tension-mediated transcription by hypoxia-inducible factors (HIF) has
      been reported to facilitate tumor progression, therapeutic resistance, and
      metastatic adaptation. One previously described target of hypoxia-mediated
      transcription is the cytokine/growth factor macrophage migration inhibitory
      factor (MIF). In studies designed to better understand hypoxia-stimulated MIF
      function, we have discovered that not only is MIF induced by hypoxia in
      pancreatic adenocarcinoma but MIF is also necessary for maximal hypoxia-induced
      HIF-1alpha expression. Cells lacking MIF are defective in hypoxia- and prolyl
      hydroxylase inhibitor-induced HIF-1alpha stabilization and subsequent
      transcription of glycolytic and angiogenic gene products. Moreover, COP9
      signalosome subunit 5 (CSN5), a component of the COP9 signalosome previously
      reported to functionally interact with MIF, has recently been shown to interact
      with and stabilize HIF-1alpha. Our results indicate that MIF interacts with CSN5
      in pancreatic cancer cells and that MIF-depleted cells display marked defects in
      hypoxia-induced CSN5/HIF-1alpha interactions. This functional interdependence
      between HIF-1alpha and MIF may represent an important and previously unrecognized
      pro-tumorigenic axis.

PMID- 17210700
TI  - An osteoprotegerin-like peptidomimetic inhibits osteoclastic bone resorption and
      osteolytic bone disease in myeloma.
AB  - Multiple myeloma is a B-cell malignancy characterized by the uncontrolled growth
      of plasma cells in the bone marrow and the development of osteolytic bone
      disease. Myeloma cells express the receptor activator of nuclear factor kappaB
      ligand (RANKL), induce RANKL expression in the bone marrow, and down-regulate
      expression of the decoy receptor osteoprotegerin, thereby promoting bone
      resorption. Targeting this system in myeloma has clear therapeutic potential.
      However, osteoprotegerin also binds tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) and prevents TRAIL-induced apoptosis of myeloma cells.
      Whether or not osteoprotegerin can bind TRAIL and prevent apoptosis in vivo and
      the relative importance of osteoprotegerin binding to TRAIL and RANKL are
      unclear. In the present study, we have investigated the ability of an
      osteoprotegerin-like peptidomimetic (OP3-4), designed to block the RANKL/RANK
      interaction, to inhibit osteoclastic bone resorption and TRAIL-induced apoptosis
      in vitro and myeloma bone disease in vivo. OP3-4 inhibited osteoclast formation
      (P < 0.01) and bone resorption (P < 0.01) in vitro. However, OP3-4 had no effect
      on TRAIL-induced apoptosis of RPMI 8226 myeloma cells. Treatment of 5T2MM myeloma
      bearing mice with OP3-4 decreased osteoclast number and the proportion of bone
      surface covered by osteoclasts (P < 0.05). Treatment also prevented the tumor
      induced decrease in cancellous bone area and the development of osteolytic
      lesions (P < 0.05). OP3-4 also reduced tumor burden when compared with the
      control (P < 0.05). These data suggest that OP3-4 and the selective inhibition of
      RANKL, but not TRAIL activity, are effective in preventing myeloma bone disease
      and offer a novel therapeutic approach to treating this aspect of myeloma.
      [Cancer Res 2007;67(1):202-8].

PMID- 17210702
TI  - TRAIL induces receptor-interacting protein 1-dependent and caspase-dependent
      necrosis-like cell death under acidic extracellular conditions.
AB  - Tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) is a
      potential anticancer agent that induces apoptosis in cancer cells but not in most
      normal cells. How tumor physiology, particularly acidic extracellular pH (pH(e)),
      would modify sensitivity of cancer cells to TRAIL-induced cell death is not
      known. We have previously shown that cancer cells, resistant to TRAIL-induced
      apoptosis at physiologic pH(e) (7.4), could be sensitized to TRAIL at acidic
      pH(e) (6.5). However, at this acidic pH(e), cell death was necrotic. We show here
      that, in spite of a necrosis-like cell death morphology, caspases are activated
      and are necessary for TRAIL-induced cell death at acidic pH(e) in HT29 human
      colon cancer cells. Furthermore, we observed that, whereas receptor-interacting
      protein (RIP) was cleaved following TRAIL treatment at physiologic pH(e) (7.4),
      it was not cleaved following TRAIL treatment at acidic pH(e) (6.5). Moreover, RIP
      degradation by geldanamycin or decrease expression of RIP by small RNA
      interference transfection inhibited TRAIL-induced necrosis at acidic pH(e),
      showing that RIP was necessary for this necrotic cell death pathway. We also show
      that RIP kinase activity was essential for this cell death pathway. Altogether,
      we show that, under acidic pH(e) conditions, TRAIL induces a necrosis-like cell
      death pathway that depends both on caspases and RIP kinase activity. Thus, our
      data suggest for the first time that RIP-dependent necrosis might be a major
      death pathway in TRAIL-based therapy in solid tumors with acidic pH(e).

PMID- 17210701
TI  - An organometallic protein kinase inhibitor pharmacologically activates p53 and
      induces apoptosis in human melanoma cells.
AB  - Unlike other tumors, melanomas harbor wild-type (WT) p53 but exhibit impaired p53
      dependent apoptosis. The mechanisms for the impaired p53 activation are poorly
      understood but may be linked to the high expression of the p53 suppressor Mdm2,
      which is found in >50% of melanoma lesions. Here, we describe an organometallic
      glycogen synthase kinase 3beta (GSK3beta) inhibitor (DW1/2) as a potent activator
      of p53 and inducer of cell death in otherwise highly chemoresistant melanoma
      cells. Using RNA interference and pharmacologic approaches, we show that p53 is
      required for the cytotoxic effects of this organometallic inhibitor. The DW1/2
      compound was barely able to induce cell death in melanoma cells with p53
      mutations, further confirming the requirement for p53-WT in the cytotoxic effects
      of the GSK3beta inhibition. Mechanistic analysis of the p53-dependent cell death
      indicated an apoptotic mechanism involving depolarization of mitochondrial
      membrane potential, caspase cleavage, and elevated NOXA expression. The effect of
      p53 was not simply due to passive up-regulation of protein expression as
      adenoviral-mediated overexpression of p53 was not able to induce cell death.
      Treatment of melanoma cells with DW1/2 was instead found to decrease levels of
      Mdm2 and Mdm4. The importance of Mdm2 down-regulation in DW1/2-induced apoptosis
      was confirmed by treating the p53-WT cells with the p53/Mdm2 antagonist Nutlin-3.
      Taken together, our data provide a new strategy for the pharmacologic activation
      of p53 in melanoma, which may be a viable approach for overcoming apoptotic
      resistance in melanoma and offer new hope for rational melanoma therapy.

PMID- 17210703
TI  - Inactivated Sendai virus particles eradicate tumors by inducing immune responses
      through blocking regulatory T cells.
AB  - UV-inactivated, replication-defective Sendai virus particles [hemagglutinating
      virus of Japan envelope (HVJ-E)] injected into murine colon carcinoma (CT26)
      tumors growing in syngeneic BALB/c mice eradicated 60% to 80% of the tumors and
      obviously inhibited the growth of the remainder. Induced adaptive antitumor
      immune responses were dominant in the tumor eradication process because the
      effect was abrogated in severe combined immunodeficient mice. Murine and human
      dendritic cells underwent dose-dependent maturation by HVJ-E in vitro. Profiles
      of cytokines secreted by dendritic cells after HVJ-E stimulation showed that the
      amount of interleukin-6 (IL-6) released was comparable to that elicited by live
      HVJ. Real-time reverse transcription-PCR and immunohistochemistry revealed that
      HVJ-E induced a remarkable infiltration of dendritic cells and CD4+ and CD8+ T
      cells into tumors. In addition, CT26-specific CTLs were induced with the evidence
      of enhanced CD8+ T-cell activation in a CD4+CD25- T cell-dependent manner. On the
      other hand, conditioned medium from dendritic cells stimulated by HVJ-E rescued
      CD4+CD25- effector T-cell proliferation from Foxp3+CD4+CD25+ regulatory T cell
      (Treg)-mediated suppression and IL-6 was presumably dominant for this phenomenon.
      We also confirmed such rescue in mice treated with HVJ-E in vivo. Moreover,
      antitumor effect of HVJ-E was significantly reduced by an in vivo blockade of IL
      6 signaling. This is the first report to show that HVJ-E alone can eradicate
      tumors and the mechanism through which it induces antitumor immune responses.
      Because it can enhance antitumor immunity and simultaneously remove Treg-mediated
      suppression, HVJ-E shows promise as a novel therapeutic for cancer immunotherapy.

PMID- 17210704
TI  - Potentiation of kinesin spindle protein inhibitor-induced cell death by
      modulation of mitochondrial and death receptor apoptotic pathways.
AB  - Targeting the mitotic motor kinesin kinesin spindle protein (KSP) is a new
      strategy for cancer therapy. We have examined the molecular events induced by KSP
      inhibition and explored possible mechanisms of resistance and sensitization of
      tumor cells to KSP inhibitors. We found that KSP inhibition induced cell death
      primarily via activation of the mitochondrial death pathway. In HeLa cells,
      inhibition of KSP by small-molecule inhibitor monastrol resulted in mitotic
      arrest and rapid caspase activation. BclXL phosphorylation and loss of
      mitochondrial membrane potential was detected before significant caspase
      activation, which was required to trigger the subsequent apoptotic pathway. In
      A549 cells, however, KSP inhibition did not induce mitochondrial damage,
      significant caspase activity, or cell death. A549 cells aberrantly exited
      mitosis, following a prolonged drug-induced arrest, and arrested in a G(1)-like
      state with 4N DNA content in a p53-dependent manner. Overexpression of BclXL
      provided a protective mechanism, and its depletion rescued the apoptotic response
      to monastrol. In addition, Fas receptor was up-regulated in A549 cells in
      response to monastrol. Treatment with Fas receptor agonists sensitized the cells
      to monastrol-induced cell death, following exit from mitosis. Thus, activation of
      the death receptor pathway offered another mechanism to enhance KSP inhibitor
      induced apoptosis. This study has elucidated cellular responses induced by KSP
      inhibitors, and the results provide insights for a more effective cancer
      treatment with these agents.

PMID- 17210705
TI  - Imaging tumors with an albumin-binding Fab, a novel tumor-targeting agent.
AB  - Association with albumin as a means to improve biodistribution and tumor
      deposition of a Fab was investigated using AB.Fab4D5, a bifunctional molecule
      derived from trastuzumab (HERCEPTIN) capable of binding albumin and tumor antigen
      HER2 (erbB2) simultaneously. AB.Fab4D5 was compared with trastuzumab and a
      trastuzumab-derived Fab (Fab4D5) for the ability to target tumors overexpressing
      HER2 in mouse mammary tumor virus/HER2 allograft models. Biodistribution was
      monitored using intravital microscopy, histology, and integrated single-photon
      emission computed tomography/computed tomography analysis. Fab4D5 tumor
      deposition was characterized by rapid but transient appearance in tumor at 2 h
      with little retention, followed by rapid accumulation in kidney by 6 h.
      Trastuzumab was slow to accumulate in tumors and slow to clear from normal
      tissues, although significant tumor deposition was achieved by 24 h. In contrast,
      AB.Fab4D5 was observed at 2 h in tumor and its presence was sustained beyond 24 h
      similar to trastuzumab. Intravital microscopy revealed that at peak tumor
      accumulation, tumor cell staining by AB.Fab4D5 was more uniform than for Fab4D5
      or trastuzumab. Similar tumor deposition was achieved for both AB.Fab4D5 and
      trastuzumab at 48 h (35.9 +/- 1.8% and 38.2 +/- 3.1% injected dose/g); however,
      AB.Fab4D5 targeted tumors more rapidly and quickly cleared from blood, leading to
      a lower overall normal tissue exposure. Importantly, unlike Fab4D5, AB.Fab4D5 did
      not accumulate in kidney, suggesting that association with albumin leads to an
      altered route of clearance and metabolism. Rapid targeting, excellent tumor
      deposition and retention, coupled with high tumor to blood ratios may make AB.Fab
      an exceptional molecule for imaging and cancer therapy.

PMID- 17210706
TI  - Multidrug resistance protein 4 protects bone marrow, thymus, spleen, and
      intestine from nucleotide analogue-induced damage.
AB  - Nucleoside-based analogues are mainstays in the treatment of cancer, viral
      infections, and inflammatory diseases. Recent studies showing that the ATP
      binding cassette transporter, multidrug resistance protein 4, is able to efflux
      nucleoside and nucleotide analogues from transfected cells suggests that the pump
      may affect the efficacy of this class of agents. However, the in vivo
      pharmacologic functions of the pump are largely unexplored. Here, using Mrp4(-/-)
      mice as a model system, and the nucleotide analogue, 9'-(2'
      phosphonylmethoxyethyl)-adenine (PMEA) as a probe, we investigate the ability of
      Mrp4 to function in vivo as an endogenous resistance factor. In the absence of
      alterations in plasma PMEA levels, Mrp4-null mice treated with PMEA exhibit
      increased lethality associated with marked toxicity in several tissues. Affected
      tissues include the bone marrow, spleen, thymus, and gastrointestinal tract. In
      addition, PMEA penetration into the brain is increased in Mrp4(-/-) mice. These
      findings indicate that Mrp4 is an endogenous resistance factor, and that the pump
      may be a component of the blood-brain barrier for nucleoside-based analogues.
      This is the first demonstration that an ATP-binding cassette transporter can
      affect in vivo tissue sensitivity towards this class of agents.

PMID- 17210707
TI  - Anti-HER2 cationic immunoemulsion as a potential targeted drug delivery system
      for the treatment of prostate cancer.
AB  - Present management of metastatic prostate cancer, which includes hormonal
      therapy, chemotherapy, and radiotherapy, are frequently palliative. Taxanes, and
      specifically docetaxel, are being extensively investigated to improve the
      survival of metastatic prostate cancer patients. Although paclitaxel exhibits a
      wide spectrum of antitumor activity, its therapeutic application is limited, in
      part, due to its low water solubility that necessitates the use of Cremophor EL,
      which is known to induce hypersensitivity reactions. Therefore, the objective of
      this present study was to assess the efficiency of paclitaxel palmitate-loaded
      anti-HER2 immunoemulsions, a targeted drug delivery system based on cationic
      emulsion covalently linked to anti-HER2 monoclonal antibody (Herceptin), in a
      well-established in vivo pharmacologic model of metastatic prostate cancer that
      overexpresses the HER2 receptor. It was clearly noted that the cationic emulsion
      and immunoemulsion did not activate the complement compared with the commercial
      and paclitaxel palmitate hydroalcoholic formulations. In addition, 10 mg/kg of
      paclitaxel palmitate-loaded immunoemulsion once weekly over 3 weeks inhibits the
      tumor growth in severe combined immunodeficient mice much more than the cationic
      emulsion (P < 0.05) and the paclitaxel palmitate formulation (P < 0.01). The
      histopathologic analysis suggested a therapeutic improvement trend in favor of
      the immunoemulsion. However, there was no significant difference in
      antimetastatic activity between the emulsion and the immunoemulsion despite the
      affinity of the immunoemulsion towards the HER2 receptor. Although the tumor
      growth was not fully inhibited, the actual results are encouraging and may lead
      to an improved therapeutic strategy of metastatic prostate cancer treatment.

PMID- 17210708
TI  - Transgenic overexpression of RasGRP1 in mouse epidermis results in spontaneous
      tumors of the skin.
AB  - RasGRP1 is a guanine nucleotide exchange factor for Ras and a receptor of the
      second messenger diacylglycerol and its ultrapotent analogues, the phorbol
      esters. We have recently shown expression of RasGRP1 in the epidermal
      keratinocytes where it can mediate Ras activation in response to the phorbol
      ester 12-O-tetradecanoylphorbol-13-acetate, a well-known mouse skin tumor
      promoter. To explore the participation of RasGRP1 in skin carcinogenesis, we
      targeted the overexpression of RasGRP1 to basal epidermal keratinocytes using the
      keratin 5 promoter. These transgenic mice were viable and indistinguishable from
      their littermates, with normal differentiation and skin architecture. However, a
      percentage of the adult transgenic population developed spontaneous skin tumors,
      mainly squamous cell papillomas. The transgene was detected in the tumors as well
      as in primary keratinocytes isolated from transgenic mice. The transgenic
      keratinocytes also displayed elevated levels of active, GTP-loaded Ras compared
      with the levels observed in keratinocytes derived from wild-type littermates. We
      noticed a correlation between tumor incidence and wounding, which suggests that
      RasGRP1 overexpression may confer sensitivity to promotional stimuli, like wound
      repair mechanisms. Interestingly, we also found elevated levels of granulocyte
      colony-stimulating factor in conditioned media derived from transgenic
      keratinocytes subjected to in vitro wounding. Taken together, these data are the
      first to provide evidence of a novel role for RasGRP1 in skin carcinogenesis and
      suggest that RasGRP1 may participate in tumorigenesis through modulation of Ras
      and autocrine pathways.

PMID- 17210709
TI  - Metronomic chemotherapy enhances the efficacy of antivascular therapy in ovarian
      cancer.
AB  - Metronomic chemotherapy is the frequent administration of low doses of
      chemotherapeutic agents targeting tumor-associated endothelial cells. We examined
      the efficacy of metronomic taxanes alone and in combination with AEE788-a dual
      epidermal growth factor receptor (EGFR) and vascular endothelial growth factor
      receptor (VEGFR) inhibitor-in an orthotopic mouse model of ovarian cancer. Growth
      modulating effects of metronomic and maximum tolerated dose (MTD) regimens on
      overall survival were tested in vivo using both chemotherapy-sensitive (HeyA8 and
      SKOV3ip1) and chemotherapy-resistant (HeyA8-MDR) models. Treated tumors were
      stained for microvessel density (CD31), proliferation index (proliferating cell
      nuclear antigen), and apoptosis (terminal deoxyribonucleotide transferase
      mediated nick-end labeling). The cytotoxic effects of MTD and metronomic dosing
      were tested with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      assays. Effects of metronomic regimens on circulating endothelial precursors
      (CEP) and tumor-specific cell-free DNA levels were assessed. In vivo, metronomic
      docetaxel resulted in significant reduction of tumor growth in the taxane
      sensitive cell lines, whereas metronomic docetaxel plus AEE788 had an additive
      effect resulting in significant prolongation in survival. Combination therapy was
      effective even in the taxane-resistant model. Metronomic chemotherapy alone and
      combined with AEE788 resulted in a decrease in the proliferative index and
      microvessel density of treated tumors, whereas combination therapy increased the
      apoptotic index (P < 0.001). In vitro, metronomic taxanes caused endothelial cell
      toxicity at 10- to 100-fold lower concentrations compared with MTD dosing.
      Metronomic regimens inhibited mobilization of CEPs (P < 0.05) and led to a
      decrease in cell-free DNA levels (P < 0.05). Our results suggest that metronomic
      taxane chemotherapy with dual EGFR and VEGFR inhibition is highly efficacious and
      should be considered for future clinical trials.

PMID- 17210710
TI  - Nitric oxide in physiologic concentrations targets the translational machinery to
      increase the proliferation of human breast cancer cells: involvement of mammalian
      target of rapamycin/eIF4E pathway.
AB  - Nitric oxide (NO) in nanomolar (nmol/L) concentrations is consistently detected
      in tumor microenvironment and has been found to promote tumorigenesis. The
      mechanism by which NO enhances tumor progression is largely unknown. In this
      study, we investigated the possible mechanisms and identified cellular targets by
      which NO increases proliferation of human breast cancer cell lines MDA-MB-231 and
      MCF-7. DETA-NONOate, a long acting NO donor, with a half-life of 20 h, was used.
      We found that NO (nmol/L) dramatically increased total protein synthesis in MDA
      MB-231 and MCF-7 and also increased cell proliferation. NO specifically increased
      the translation of cyclin D1 and ornithine decarboxylase (ODC) without altering
      their mRNA levels or half-lives. Critical components in the translational
      machinery, such as phosphorylated mammalian target of rapamycin (mTOR) and its
      downstream targets, phosphorylated eukaryotic translation initiation factor and
      p70 S6 kinase, were up-regulated following NO treatment, and inhibition of mTOR
      with rapamycin attenuated NO induced increase of cyclin D1 and ODC. Activation of
      translational machinery was mediated by NO-induced up-regulation of the
      Raf/mitogen-activated protein/extracellular signal-regulated kinase (ERK)
      kinase/ERK (Raf/MEK/ERK) and phosphatidylinositol 3-kinase (PI-3 kinase)/Akt
      signaling pathways. Up-regulation of the Raf/MEK/ERK and PI-3 kinase/Akt pathways
      by NO was found to be mediated by activation of Ras, which was cyclic guanosine
      3',5'-monophosphate independent. Furthermore, inactivation of Ras by farnesyl
      transferase inhibitor or K-Ras small interfering RNA attenuated NO-induced
      increase in proliferation signaling and cyclin D1 and ODC translation, further
      confirming the involvement of Ras activation during NO-induced cell
      proliferation.

PMID- 17210711
TI  - Delivery of CCL21 to metastatic disease improves the efficacy of adoptive T-cell
      therapy.
AB  - Adoptive T-cell transfer has achieved significant clinical success in advanced
      melanoma. However, therapeutic efficacy is limited by poor T-cell survival after
      adoptive transfer and by inefficient trafficking to tumor sites. Here, we report
      that intratumoral expression of the chemokine CCL21 enhances the efficacy of
      adoptive T-cell therapy in a mouse model of melanoma. Based on our novel
      observation that CCL21 is highly chemotactic for activated OT-1 T cells in vitro
      and down-regulates expression of CD62L, we hypothesized that tumor cell-mediated
      expression of this chemokine might recruit, and retain, adoptively transferred T
      cells to the sites of tumor growth. Mice bearing metastatic tumors stably
      transduced with CCL21 survived significantly longer following adoptive T-cell
      transfer than mice bearing non-CCL21-expressing tumors. However, although we
      could not detect increased trafficking of the adoptively transferred T cells to
      tumors, tumor-expressed CCL21 promoted the survival and cytotoxic activity of the
      adoptively transferred T cells and led to the priming of antitumor immunity
      following T-cell transfer. To translate these observations into a protocol of
      real clinical usefulness, we showed that adsorption of a retrovirus encoding
      CCL21 to OT-1 T cells before adoptive transfer increased the therapeutic efficacy
      of a subsequently administered dose of OT-1 T cells, resulting in cure of
      metastatic disease and the generation of immunologic memory in the majority of
      treated mice. These studies indicate a promising role for CCL21 in enhancing the
      therapeutic efficacy of adoptive T-cell therapy.

PMID- 17210712
TI  - Pegylated recombinant human arginase (rhArg-peg5,000mw) inhibits the in vitro and
      in vivo proliferation of human hepatocellular carcinoma through arginine
      depletion.
AB  - Hepatocellular carcinoma (HCC) is believed to be auxotrophic for arginine through
      the lack of expression of argininosuccinate synthetase (ASS). The successful use
      of the arginine-depleting enzyme arginine deiminase (ADI) to treat ASS-deficient
      tumors has opened up new possibilities for effective cancer therapy.
      Nevertheless, many ASS-positive HCC cell lines are found to be resistant to ADI
      treatment, although most require arginine for proliferation. Thus far, an
      arginine-depleting enzyme for killing ASS-positive tumors has not been reported.
      Here, we provide direct evidence that recombinant human arginase (rhArg) inhibits
      ASS-positive HCCs. All the five human HCC cell lines we used were sensitive to
      rhArg but ADI had virtually no effect on these cells. They all expressed ASS, but
      not ornithine transcarbamylase (OTC), the enzyme that converts ornithine, the
      product of degradation of arginine with rhArg, to citrulline, which is converted
      back to arginine via ASS. Transfection of HCC cells with OTC resulted in
      resistance to rhArg. Thus, OTC expression alone may be sufficient to induce rhArg
      resistance in ASS-positive HCC cells. This surprising correlation between the
      lack of OTC expression and sensitivity of ASS-positive HCC cells shows that OTC
      deficient HCCs are sensitive to rhArg-mediated arginine depletion. Therefore,
      pretreatment tumor gene expression profiling of ASS and OTC could aid in
      predicting tumor response to arginine depletion with arginine-depleting enzymes.
      We have also shown that the rhArg native enzyme and the pegylated rhArg (rhArg
      peg(5,000mw)) gave similar anticancer efficacy in vitro. Furthermore, the growth
      of the OTC-deficient Hep3B tumor cells (ASS-positive and ADI-resistant) in mice
      was inhibited by treatment with rhArg-peg(5,000mw), which is active alone and is
      synergistic in combination with 5-fluorouracil. Thus, our data suggest that rhArg
      peg(5,000mw) is a novel agent for effective cancer therapy.

PMID- 17210714
TI  - [177Lu]pertuzumab: experimental therapy of HER-2-expressing xenografts.
AB  - Pertuzumab (Omnitarg) is a novel antibody against HER-2, domain II. HER-2 is a
      tyrosine kinase receptor that is overexpressed in several carcinomas, especially
      breast cancer. Pertuzumab, labeled with the low-energy beta emitter (177)Lu,
      might be a candidate for targeted radiotherapy of disseminated HER-2-positive
      micrometastases. The radiolabeled antibody [(177)Lu]pertuzumab showed favorable
      targeting properties in BALB/c (nu/nu) mice with HER-2-overexpressing xenografts.
      The absorbed dose in tumors was more than five times higher than the absorbed
      dose in blood and more than seven times the absorbed dose in any other normal
      organ. Experimental therapy showed that [(177)Lu]pertuzumab delayed tumor
      progression compared with controls (no treatment, P < 0.0001; nonlabeled
      pertuzumab antibody, P < 0.0001; and (177)Lu-labeled irrelevant antibody, P <
      0.01). No adverse side effects of the treatment could be detected. Thus, the
      experimental results support the planning of clinical studies applying
      [(177)Lu]pertuzumab for therapy.

PMID- 17210713
TI  - Adamantyl-substituted retinoid-related molecules bind small heterodimer partner
      and modulate the Sin3A repressor.
AB  - 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (CD437/AHPN) and
      4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC/MM002) are
      inducers of apoptosis of malignant cells both in vitro and in vivo. Numerous
      mechanisms have been proposed for how these compounds exert this effect. This
      report shows that AHPN/3-Cl-AHPC binds specifically to the orphan nuclear
      receptor small heterodimer partner (SHP; NR0B2), and this binding promotes
      interaction of the receptor with a corepressor complex that minimally contains
      Sin3A, N-CoR, histone deacetylase 4, and HSP90. Formation of the SHP-Sin3A
      complex is essential for the ability of AHPN and 3-Cl-AHPC to induce apoptosis,
      as both knockout SHP and knockdown of Sin3A compromise the proapoptotic activity
      of these compounds but not other apoptosis inducers. These results suggest that
      AHPN/3-Cl-AHPC and their analogues are SHP ligands and their induction of
      apoptosis is mediated by their binding to the SHP receptor.

PMID- 17210715
TI  - ADAM10 inhibition of human CD30 shedding increases specificity of targeted
      immunotherapy in vitro.
AB  - CD30 is a transmembrane protein selectively overexpressed on many human lymphoma
      cells and therefore an interesting target for antibody-based immunotherapy.
      However, binding of therapeutic antibodies stimulates a juxtamembrane cleavage of
      CD30 leading to a loss of target antigen and an enhanced release of the soluble
      ectodomain of CD30 (sCD30). Here, we show that sCD30 binds to CD30 ligand (CD153)
      expressing non-target cells. Because antibodies bind to sCD30, this results in
      unwanted antibody binding to these cells via sCD30 bridging. To overcome shedding
      dependent damage of normal cells in CD30-specific immunotherapy, we analyzed the
      mechanism involved in the release. Shedding of CD30 can be enhanced by protein
      kinase C (PKC) activation, implicating the disintegrin metalloproteinase ADAM17
      but not free cytoplasmic calcium. However, antibody-induced CD30 shedding is
      calcium dependent and PKC independent. This shedding involved the related
      metalloproteinase ADAM10 as shown by the use of the preferential ADAM10 inhibitor
      GI254023X and by an ADAM10-deficient cell line generated from embryonically
      lethal ADAM10(-/-) mouse. In coculture experiments, the antibody-induced transfer
      of sCD30 from the human Hodgkin's lymphoma cell line L540 to the CD30-negative
      but CD153-expressing human mast cell line HMC-1 was inhibited by GI254023X. These
      findings suggest that selective metalloproteinase inhibitors blocking antibody
      induced shedding of target antigens could be of therapeutic value to increase the
      specificity and reduce side effects of immunotherapy with monoclonal antibodies.

PMID- 17210716
TI  - Mechanisms of mitotic cell death induced by chemotherapy-mediated G2 checkpoint
      abrogation.
AB  - The novel concept of anticancer treatment termed "G(2) checkpoint abrogation"
      aims to target p53-deficient tumor cells and is currently explored in clinical
      trials. The anticancer drug UCN-01 is used to abrogate a DNA damage-induced G(2)
      cell cycle arrest leading to mitotic entry and subsequent cell death, which is
      poorly defined as "mitotic cell death" or "mitotic catastrophe." We show here
      that UCN-01 treatment results in a mitotic arrest that requires an active mitotic
      spindle checkpoint, involving the function of Mad2, Bub1, BubR1, Mps1, Aurora B,
      and survivin. During the mitotic arrest, hallmark parameters of the mitochondria
      associated apoptosis pathway become activated. Interestingly, this apoptotic
      response requires the spindle checkpoint protein Mad2, suggesting a proapoptotic
      function for Mad2. However, although survivin and Aurora B are also required for
      the mitotic arrest, both proteins are part of an antiapoptotic pathway that
      restrains the UCN-01-induced apoptosis by promoting hyperphosphorylation of Bcl-2
      and by inhibiting the activation of Bax. Consequently, inhibition of the
      antiapoptotic pathway by genetic ablation of survivin or by pharmacologic
      inhibitors of Aurora B or cyclin-dependent kinase 1 lead to a significant
      enhancement of apoptosis and therefore act synergistically with UCN-01. Thus, by
      defining the mechanism of cell death on G(2) checkpoint abrogation we show a
      highly improved strategy for an anticancer treatment by the combined use of UCN
      01 with abrogators of the survivin/Aurora B-dependent antiapoptotic pathway that
      retains the selectivity for p53-defective cancer cells.

PMID- 17210717
TI  - Inhibition of histone deacetylation does not block resilencing of p16 after 5-aza
      2'-deoxycytidine treatment.
AB  - Epigenetic drugs are in use in clinical trials of various human cancers and are
      potent at reactivating genes silenced by DNA methylation and chromatin
      modifications. We report here the analysis of a set of normal fibroblast and
      cancer cell lines after combination treatment with the DNA methyltransferase
      inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) and the histone deacetylase
      inhibitor 4-phenylbutyric acid (PBA). Low doses of the drug combination caused
      cell cycle arrest, whereas high doses induced apoptosis in T24 bladder carcinoma
      cells. Both p16 (CDKN2A/INK4) and p21 (CIP1/SDI1/WAF1) expression were induced to
      similar levels in normal and cancer cells in a dose-dependent fashion after
      combination treatments. We detected a distinct increase of histone H3 acetylation
      at lysine 9/14 near the transcription start sites, in both LD419 normal
      fibroblasts and T24 bladder carcinoma cells, whereas the acetylation changes in
      the p21 locus were less apparent. Interestingly, the levels of trimethylation of
      histone H3 on lysine 9, which usually marks inactive chromatin regions and was
      associated with the p16 promoter in silenced T24 cells, did not change after drug
      treatments. Furthermore, we provide evidence that the remethylation of the p16
      promoter CpG island in T24 cells after 5-aza-CdR treatment cannot be halted by
      subsequent continuous PBA treatment. The p16 gene is resilenced with kinetics
      similar to 5-aza-CdR only-treated cells, which is also marked by a localized loss
      of histone acetylation at the transcription start site. Altogether, our data
      provide new insights into the mechanism of epigenetic drugs and have important
      implications for epigenetic therapy.

PMID- 17210718
TI  - High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated
      with the absence of lymph node metastases in patients with large early-stage
      cervical cancer.
AB  - In a prospective study, we have examined the tumor-specific immune response in a
      group of 59 patients with human papillomavirus (HPV) 16-positive (HPV16(+))
      induced or HPV18(+)-induced cervical cancer. Local antitumor immunity was
      analyzed by the enumeration of tumor-infiltrating dendritic cells and CD4+, CD8+,
      and regulatory T cells as well as by calculation of the ratio of CD8+/CD4+ T
      cells and CD8+/regulatory T cells. Systemic tumor-specific immunity was assessed
      by determination of the HPV E6- and/or E7-specific T-cell response in the blood
      of these patients. Finally, these variables were evaluated with respect to known
      histopathologic prognostic variables, including the absence (LN-) or presence
      (LN+) of lymph node metastases. Stratification according to the lymph node status
      of patients revealed a significantly stronger CD8+ T-cell tumor infiltration, a
      higher CD8+/CD4+ T-cell ratio, and higher CD8+/regulatory T-cell ratio in the
      group of patients in which the tumor failed to metastasize to the tumor-draining
      lymph node. Subdivision according to the presence (IR+) or absence (IR-) of
      circulating HPV-specific T cells disclosed that the highest number of tumor
      infiltrating CD8+ T cells was found in the group of LN- patients displaying a
      concomitant systemic tumor-specific immune response (LN-IR+). CD8+ T-cell
      infiltration in LN-IR- patients was comparable with that of LN+ patients. In
      cervical cancer, the absence of lymph node metastases is strongly associated with
      a better prognosis. Our data indicate that, especially in a subgroup of LN-
      patients, a strong and effective interaction between immune system and tumor
      exists. This subgroup of cervical cancer patients may have the best prognosis.

PMID- 17210719
TI  - Tumor-induced oxidative stress perturbs nuclear factor-kappaB activity-augmenting
      tumor necrosis factor-alpha-mediated T-cell death: protection by curcumin.
AB  - Cancer patients often exhibit loss of proper cell-mediated immunity and reduced
      effector T-cell population in the circulation. Thymus is a major site of T-cell
      maturation, and tumors induce thymic atrophy to evade cellular immune response.
      Here, we report severe thymic hypocellularity along with decreased thymic
      integrity in tumor bearer. In an effort to delineate the mechanisms behind such
      thymic atrophy, we observed that tumor-induced oxidative stress played a critical
      role, as it perturbed nuclear factor-kappaB (NF-kappaB) activity. Tumor-induced
      oxidative stress increased cytosolic IkappaBalpha retention and inhibited NF
      kappaB nuclear translocation in thymic T cells. These NF-kappaB-perturbed cells
      became vulnerable to tumor-secreted tumor necrosis factor (TNF)-alpha (TNF-alpha)
      mediated apoptosis through the activation of TNF receptor-associated protein
      death domain-associated Fas-associated protein death domain and caspase-8.
      Interestingly, TNF-alpha-depleted tumor supernatants, either by antibody
      neutralization or by TNF-alpha-small interfering RNA transfection of tumor cells,
      were unable to kill T cell effectively. When T cells were overexpressed with NF
      kappaB, the cells became resistant to tumor-induced apoptosis. In contrast, when
      degradation-defective IkappaBalpha (IkappaBalpha super-repressor) was introduced
      into T cells, the cells became more vulnerable, indicating that inhibition of NF
      kappaB is the reason behind such tumor/TNF-alpha-mediated apoptosis. Curcumin
      could prevent tumor-induced thymic atrophy by restoring the activity of NF
      kappaB. Further investigations suggest that neutralization of tumor-induced
      oxidative stress and restoration of NF-kappaB activity along with the reeducation
      of the TNF-alpha signaling pathway can be the mechanism behind curcumin-mediated
      thymic protection. Thus, our results suggest that unlike many other anticancer
      agents, curcumin is not only devoid of immunosuppressive effects but also acts as
      immunorestorer in tumor-bearing host.

PMID- 17210720
TI  - Vaccination against the forkhead family transcription factor Foxp3 enhances tumor
      immunity.
AB  - Depletion of CD4+CD25+ regulatory T cells (Treg) by treatment with alphaCD25
      antibody synergizes with vaccination protocols to engender protective immunity in
      mice. The effectiveness of targeting CD25 to eliminate Treg is limited by the
      fact that CD25, the low-affinity interleukin-2 receptor, is up-regulated on
      conventional T cells. At present, foxp3 is the only product known to be
      exclusively expressed in Treg of mice. However, foxp3 is not expressed on the
      cell surface and hence cannot be targeted with antibodies. In this study, we
      tested the hypothesis that vaccination of mice against foxp3, a self-antigen
      expressed also in the thymus, is capable of stimulating foxp3-specific CTL that
      will cause the depletion of Treg and enhanced antitumor immunity. Vaccination of
      mice with foxp3 mRNA-transfected dendritic cells elicited a robust foxp3-specific
      CTL response and potentiated vaccine-induced protective immunity comparably with
      that of alphaCD25 antibody administration. In contrast to alphaCD25 antibody
      treatment, repeated foxp3 vaccination did not interfere with vaccine-induced
      protective immunity. Importantly, foxp3 vaccination led to the preferential
      depletion of foxp3-expressing Treg in the tumor but not in the periphery, whereas
      alphaCD25 antibody treatment led to depletion of Treg in both the tumor and the
      periphery. Targeting foxp3 by vaccination offers a specific and simpler protocol
      for the prolonged control of Treg that may be associated with reduced risk of
      autoimmunity, introducing an approach whereby specific depletion of cells is not
      limited to targeting products expressed on the cell surface.

PMID- 17210721
TI  - RET/papillary thyroid carcinoma oncogenic signaling through the Rap1 small
      GTPase.
AB  - RET/papillary thyroid carcinoma (PTC) oncoproteins result from the in-frame
      fusion of the RET receptor tyrosine kinase with protein dimerization motifs
      encoded by heterologous genes. Here, we show that RET/PTC1 activates the Rap1
      small GTPase. The activation of Rap1 was dependent on the phosphorylation of RET
      Tyr(1062). RET/PTC1 recruited a complex containing growth factor receptor binding
      protein 2-associated binding protein 1 (Gab1), CrkII (v-crk sarcoma virus CT10
      oncogene homologue II), and C3G (Rap guanine nucleotide exchange factor 1). By
      using dominant-negative and small interfering duplex (small interfering RNA)
      oligonucleotides, we show that RET/PTC1-mediated Rap1 activation was dependent on
      CrkII, C3G, and Gab1. Activation of Rap1 was involved in the RET/PTC1-mediated
      stimulation of the BRAF kinase and the p42/p44 mitogen-activated protein kinases.
      Proliferation and stress fiber formation of RET/PTC1-expressing PC Cl 3 thyroid
      follicular cells were inhibited by the dominant-negative Rap1(N17) and by Rap1
      specific GTPase-activating protein. Thus, Rap1 is a downstream effector of
      RET/PTC and may contribute to the transformed phenotype of RET/PTC-expressing
      thyrocytes.

PMID- 17210722
TI  - Down-regulation of type I insulin-like growth factor receptor increases
      sensitivity of breast cancer cells to insulin.
AB  - The type I insulin-like growth factor receptor (IGF1R) and insulin receptor (IR)
      are structurally and functionally related heterotetrameric receptors. Activation
      of IGF1R has been shown to regulate breast cancer cell biology, and it has become
      an attractive therapeutic target. Most strategies have focused on targeting IGF1R
      alone without affecting IR levels given the known physiologic functions of IR.
      Human breast cancer cell lines and tissues revealed mRNA expression of both IGF1R
      and IR. Because alphabeta chains of IGF1R and IR form hybrid receptors, we
      hypothesized that agents solely targeting IGF1R may affect tumor biology mediated
      by IGF1R/IR hybrids and IR. We used small interfering RNA (siRNA) technology to
      specifically down-regulate IGF1R by 60% to 80% in the MDA-435/LCC6 cell line,
      which was sufficient to diminish activation of IGF1R by IGF-I. IGF1R down
      regulation by siRNA did not affect IR levels but, interestingly, sensitized cells
      to insulin activation of downstream signaling pathways in several breast cancer
      cell lines. IGF1R siRNA treatment diminished hybrid receptor formation,
      suggesting that specific down-regulation of IGF1R resulted in enhanced holo-IR
      formation. In addition, IGF1R down-regulation increased insulin binding
      consistent with the formation of an increased number of holo-IR on the cell
      surface. Accordingly, insulin-stimulated glucose uptake was enhanced on IGF1R
      down-regulation. In conclusion, our data suggest that specific siRNA targeting of
      IGF1R alone in breast cancer increases insulin sensitivity. Because IR also
      activates signaling pathways similar to IGF1R in breast cancer cells, agents
      targeting both receptors may be necessary to disrupt the malignant phenotype
      regulated by this growth factor system.

PMID- 17210723
TI  - Establishment of human colon cancer cell lines from fresh tumors versus
      xenografts: comparison of success rate and cell line features.
AB  - Obtaining representative human colon cancer cell lines from fresh tumors is
      technically difficult. Using 32 tumor fragments from patients with colon cancer,
      the present study shows that prior xenograft leads to more efficient cell line
      establishment compared with direct establishment from fresh tumors (P < 0.05).
      From 26 tumor specimens, we successfully established 20 tumor xenografts in nude
      mice (77%); among 19 of these xenografts, 9 (47%) led to cell lines, including
      four from liver metastases. Only 3 of 31 tumor specimens (9.7%) grew immediately
      in vitro, and all were derived from primary tumors. To compare major phenotypic
      and genotypic characteristics of human colon cancer cell lines derived from the
      same tumor fragment using two protocols, the two pairs of cell lines obtained
      from 2 of 32 tumor fragments were extensively studied. They displayed similar
      morphology and were able to form compact spheroids. Chemosensitivity to 5
      fluorouracil, CPT11, and L-OHP differed between cell lines obtained from patient
      tumors and those derived from xenografts. Matched cell lines shared a common core
      of karyotype alterations and distinctive additional chromosomal aberrations.
      Expression levels of genes selected for their role in oncogenesis evaluated by
      real-time quantitative PCR were found to be statistically correlated whatever the
      in vitro culture model used. In conclusion, xenotransplantation in mice of tumor
      fragments before establishment of cell lines enables generation of more novel
      human cancer cell lines for investigation of colon cancer cell biology, opening
      up the opportunity of reproducing the diversity of this disease.

PMID- 17210724
TI  - Allelic loss in a minimal region on chromosome 16q24 is associated with vitreous
      seeding of retinoblastoma.
AB  - In addition to RB1 gene mutations, retinoblastomas frequently show gains of 1q
      and 6p and losses of 16q. To identify suppressor genes on 16q, we analyzed 22
      short tandem repeat loci in 58 patients with known RB1 mutations. A subset of
      tumors was also investigated by conventional and matrix comparative genomic
      hybridization. In 40 of 58 (69%) tumors, we found no loss of heterozygosity (LOH)
      at any 16q marker. LOH was detected in 18 of 58 (31%) tumors, including five with
      allelic imbalance at some markers. In one tumor LOH was only observed at 16q24.
      As the parental origin of allele loss was unbiased, an imprinted locus is
      unlikely to be involved. Analysis of gene expression by microarray hybridization
      and quantitative RT real-time PCR did not identify a candidate suppressor in
      16q24. Cadherin 13 (CDH13), CBFA2T3, and WFDC1, which are candidate suppressors
      in other tumor entities with 16q24 loss, did not show loss of expression. In
      addition, mutation and methylation analysis showed no somatic alteration of
      CDH13. Results in all tumors with chromosome 16 alterations define a single
      minimal deleted region of 5.7 Mb in the telomeric part of 16q24 with the
      centromeric boundary defined by retention of heterozygosity for a single
      nucleotide variant in exon 10 of CDH13 (Mb 82.7). Interestingly, clinical
      presentation of tumors with and without 16q alterations was distinct.
      Specifically, almost all retinoblastomas with 16q24 loss showed diffuse
      intraocular seeding. This suggests that genetic alterations in the minimal
      deleted region are associated with impaired cell-to-cell adhesion.

PMID- 17210725
TI  - The terminology issue for myeloid-derived suppressor cells.

PMID- 17210727
TI  - Underinsurance and key health outcomes for children with special health care
      needs.
AB  - OBJECTIVE: The objective was to examine the relationship between underinsurance
      and other core outcomes for children with special health care needs. METHODS:
      This study analyzed data from the National Survey of Children With Special Health
      Care Needs. Two alternative definitions of underinsurance, designated attitudinal
      and economic, were investigated. Logistic regression models in which the response
      variables were the child's status for each of the target core outcomes and
      underinsurance status was a dichotomous predictor variable were created. In
      addition to underinsurance status, 10 other predictor variables were included in
      the model. RESULTS: Underinsurance is associated with the Maternal and Child
      Health Bureau core outcomes for children with special health care needs related
      to satisfaction with care and partnering with families in decision-making, access
      to a medical home, community-based service delivery that is easy to use, and
      access to services to make transitions to adulthood. In each case, children with
      special health care needs who were underinsured had significantly poorer outcomes
      than did children who were adequately insured. CONCLUSIONS: Although these
      results cannot clarify the cause of poorer outcomes, there are clear negative
      effects associated with the problem of underinsurance. Inadequate health care
      coverage for children with special health care needs may save dollars in the
      short-term but, if other outcomes are compromised, then children, their families,
      and society at large may pay a price in the longer term.

PMID- 17210728
TI  - Impact of newborn skin-cleansing with chlorhexidine on neonatal mortality in
      southern Nepal: a community-based, cluster-randomized trial.
AB  - OBJECTIVE: Hospital-based data from Africa suggest that newborn skin-cleansing
      with chlorhexidine may reduce neonatal mortality. Evaluation of this intervention
      in the communities where most births occur in the home has not been done. Our
      objective was to assess the efficacy of a 1-time skin-cleansing of newborn
      infants with 0.25% chlorhexidine on neonatal mortality. METHODS: The design was a
      community-based, placebo-controlled, cluster-randomized trial in Sarlahi District
      in southern Nepal. Newborn infants were cleansed with infant wipes that contained
      0.25% chlorhexidine or placebo solution as soon as possible after delivery in the
      home (median: 5.8 hours). The primary outcome was all-cause mortality by 28 days.
      After the completion of the randomized phase, all newborns in study clusters were
      converted to chlorhexidine treatment for the subsequent 9 months. RESULTS: A
      total of 17,530 live births occurred in the enrolled sectors, 8650 and 8880 in
      the chlorhexidine and placebo groups, respectively. Baseline characteristics were
      similar in the treatment groups. Intention-to-treat analysis among all live
      births showed no impact of the intervention on neonatal mortality. Among live
      born infants who actually received their assigned treatment (98.7%), there was a
      nonsignificant 11% lower neonatal mortality rate among those who were treated
      with chlorhexidine compared with placebo. Low birth weight infants had a
      statistically significant 28% reduction in neonatal mortality; there was no
      significant difference among infants who were born weighing > or = 2500 g. After
      conversion to active treatment in the placebo clusters, there was a 37% reduction
      in mortality among low birth weight infants in the placebo clusters versus no
      change in the chlorhexidine clusters. CONCLUSIONS: Newborn skin-wiping with
      chlorhexidine solution once, soon after birth, reduced neonatal mortality only
      among low birth weight infants. Evidence from additional trials is needed to
      determine whether this inexpensive and simple intervention could improve survival
      significantly among low birth weight infants in settings where home delivery is
      common and hygiene practices are poor.

PMID- 17210730
TI  - Igkappa allelic inclusion is a consequence of receptor editing.
AB  - The discovery of lymphocytes bearing two light chains in mice carrying self
      reactive antibody transgenes has challenged the "one lymphocyte-one antibody"
      rule. However, the extent and nature of allelically included cells in normal mice
      is unknown. We show that 10% of mature B cells coexpress both Igkappa alleles.
      These cells are not the result of failure in allelic exclusion per se, but arise
      through receptor editing. We find that under physiological conditions, editing
      occurs both by deletion and by inclusion with equal probability. In addition, we
      demonstrate that B lymphocytes carrying two B-cell receptors are recruited to
      germinal center reactions, and thus fully participate in humoral immune
      responses. Our data measure the scope of allelic inclusion and provide a
      mechanism whereby autoreactive B cells might "escape" central tolerance.

PMID- 17210729
TI  - Dendritic cell-expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells
      restore normoglycemia in diabetic NOD mice.
AB  - Most treatments that prevent autoimmune diabetes in nonobese diabetic (NOD) mice
      require intervention at early pathogenic stages, when insulitis is first
      developing. We tested whether dendritic cell (DC)-expanded, islet antigen
      specific CD4+ CD25+ suppressor T cells could treat diabetes at later stages of
      disease, when most of the insulin-producing islet beta cells had been destroyed
      by infiltrating lymphocytes. CD4+ CD25+ CD62L+ regulatory T cells (T reg cells)
      from BDC2.5 T cell receptor transgenic mice were expanded with antigen-pulsed DCs
      and IL-2, and were then injected into NOD mice. A single dose of as few as
      5x10(4) of these islet-specific T reg cells blocked diabetes development in
      prediabetic 13-wk-old NOD mice. The T reg cells also induced long-lasting
      reversal of hyperglycemia in 50% of mice in which overt diabetes had developed.
      Successfully treated diabetic mice had similar responses to glucose challenge
      compared with nondiabetic NOD mice. The successfully treated mice retained
      diabetogenic T cells, but also had substantially increased Foxp3+ cells in
      draining pancreatic lymph nodes. However, these Foxp3+ cells were derived from
      the recipient mice and not the injected T reg cells, suggesting a role for
      endogenous T reg cells in maintaining tolerance after treatment. Therefore,
      inoculation of DC-expanded, antigen-specific suppressor T cells has considerable
      efficacy in ameliorating ongoing diabetes in NOD mice.

PMID- 17210731
TI  - Induced sensitization of tumor stroma leads to eradication of established cancer
      by T cells.
AB  - Targeting cancer cells, as well as the nonmalignant stromal cells cross
      presenting the tumor antigen (Ag), can lead to the complete destruction of well
      established solid tumors by adoptively transferred Ag-specific cytotoxic T
      lymphocytes (CTLs). If, however, cancer cells express only low levels of the Ag,
      then stromal cells are not destroyed, and the tumor escapes as Ag loss variants.
      We show that treating well-established tumors expressing low levels of Ag with
      local irradiation or a chemotherapeutic drug causes sufficient release of Ag to
      sensitize stromal cells for destruction by CTLs. This was shown directly using
      high affinity T cell receptor tetramers for visualizing the transient appearance
      of tumor-specific peptide-MHC complexes on stromal cells. Maximum loading of
      tumor stroma with cancer Ag occurred 2 d after treatment and coincided with the
      optimal time for T cell transfer. Under these conditions, tumor rejection was
      complete. These findings may set the stage for developing rational clinical
      protocols for combining irradiation or chemotherapy with CTL therapy.

PMID- 17210732
TI  - Intrathecal morphine reduces breakthrough pain during labour epidural analgesia.
AB  - BACKGROUND: When using the combined spinal-epidural (CSE) technique for labour
      analgesia, parturients often experience breakthrough pain after the spinal
      medication has receded. We tested the hypothesis that a small dose of intrathecal
      morphine would reduce breakthrough pain. METHODS: This was a randomized, double
      blind, placebo-controlled trial. Subjects were randomized to receive either 100
      microg of morphine (MS) or placebo (PLCB) with the spinal injection of
      bupivacaine and fentanyl. Assessments included need for supplementation during
      labour analgesia, use of pain medications for 24 h after delivery, and side
      effects. The primary end-point was the rate of breakthrough pain. RESULTS: Sixty
      subjects were enrolled, 55 subjects completed the trial. The MS group had a
      significantly lower rate of breakthrough pain than the PLCB group [0.6 (0.6) vs
      1.1 (0.8) episodes per patient; P < 0.01], and longer time to first episode of
      breakthrough pain (300 vs 180 min; P = 0.03). The MS group used 75% less opioid
      medications during the subsequent 24 h, but had a 17% incidence of nausea.
      CONCLUSIONS: The addition of small dose of morphine to the spinal component of
      the CSE technique improved the effectiveness of epidural labour analgesia and
      reduced the need for pain medications over 24 h, but resulted in a small increase
      in nausea.

PMID- 17210733
TI  - Asynchronous administration of xenon and hypothermia significantly reduces brain
      infarction in the neonatal rat.
AB  - BACKGROUND: Neonatal asphyxia causes long-term neurological and behavioural
      impairment in the developing brain. Concurrent administration of xenon and
      hypothermia synergistically reduces long-term damage in a rat model of neonatal
      asphyxia. This study sought to investigate whether asynchronous administration of
      xenon and hypothermia is capable of combining synergistically to provide
      neuroprotection. METHODS: Seven-day-old rats were subjected to right common
      carotid artery occlusion followed by 90 min hypoxia with 8% oxygen. After a 1 h
      recovery period, rats received asynchronous administration of mild hypothermia
      (35 degrees C) and xenon (20%) with a 1 or 5 h gap between interventions, xenon
      (20%) alone, or mild hypothermia (35 degrees C) alone. Infarct volume in the
      brain was measured 4 days after injury. RESULTS: Administration of hypothermia or
      xenon alone, 1 and 6 h after the hypoxic ischaemic insult, respectively, provided
      no neuroprotection. Asynchronous administration of xenon and hypothermia at a 1 h
      interval produced a significant reduction in infarct volume [93 (7) vs 74 (8); P
      < 0.05]. Reduction in infarct volume was also present when hypothermia and xenon
      were asynchronously administered with an intervening gap of 5 h [97 (5) vs 83
      (3); P < 0.05]. CONCLUSIONS: This finding provides a rationale for investigating
      the combined use of hypothermia and xenon in a progressive manner for the
      management of neonatal asphyxia. Thus, hypothermia can be administrated at the
      site of delivery and xenon can be administered later.

PMID- 17210734
TI  - Bedside prediction of the central venous catheter insertion depth.
AB  - BACKGROUND: The carina level has been shown to be near the pericardial reflection
      and can easily be identified as a landmark on a routine chest radiography. The
      purpose of this study was to reveal a simple method to predict the adequate
      central venous catheter (CVC) depth, hereby facilitating safe positioning of the
      CVC tip. METHODS: Central venous catheterization was performed via the right
      internal jugular vein (IJV) or the right subclavian vein (SCV). The CVC was
      placed at a depth derived by adding the length between the needle insertion point
      and the clavicular notch and the vertical length between the clavicular notch and
      the carina on the chest radiograph. The distance between the CVC tip and the
      carina was measured on the postoperative chest radiograph. RESULTS: The tip
      position of 100 CVCs placed via the right IJV was 0.1 (1.1) cm [mean (SD)] below
      the carina (95% CI: 0.3 cm below carina-0.2 cm above carina) and the tip position
      of 153 CVCs placed via the right SCV was 0.0 (1.2) cm [mean (SD)] below the
      carina (95% CI: 0.2 cm below carina-0.2 cm above carina). There were nine
      outliers (two in IJV group and seven in SCV group). CONCLUSIONS: When CVCs are
      inserted to a depth derived by adding the length between the needle insertion
      point and the clavicular notch and the vertical length between the clavicular
      notch and the carina, the CVC tip can be reliably placed near the carina level.

PMID- 17210735
TI  - Autonomic effects of epidural and intravenous fentanyl.
AB  - BACKGROUND: We tested the hypothesis that there is greater suppression of
      autonomic reflexes during general anaesthesia when fentanyl is administered
      epidurally than when it is given intravenously. METHODS: Ten volunteers were
      anaesthetized with desflurane. Noxious stimuli of variable intensity were then
      delivered by tetanic electrical stimuli. Heart rate, arterial pressure, and
      pupillary dilation in response to these stimuli defined nociception. Seven of
      these volunteers participated twice using a crossover design: they received i.v.
      fentanyl on one study day and epidurally on the other. Autonomic responses to
      alternative tetanic stimuli at L4 and C5 dermatomes were measured every 5 min for
      3 h after fentanyl administration. RESULTS: After a brief redistribution period,
      plasma fentanyl concentrations were virtually identical on both days. After
      stimulation of the L4 dermatome only, block of pupillary reflex dilation was
      greater by 47 (22)% after epidural fentanyl compared with i.v. fentanyl. Time to
      maximal depression of reflex dilation after L4 stimulation was 41 (13) min.
      Arterial pressure and heart rate decreased after fentanyl by either route but
      there were no differences observed between L4 and C5 stimulations. CONCLUSION: We
      conclude that during general anaesthesia, epidural fentanyl enhances
      antinociception by a spinal mechanism which can be detected by pupillary dilation
      but not by changes in arterial pressure or heart rate.

PMID- 17210736
TI  - Corresponding minimum alveolar concentrations of isoflurane and
      isoflurane/nitrous oxide have divergent effects on thalamic nociceptive
      signalling.
AB  - BACKGROUND: Suppression of nociceptive signalling in the thalamus is considered
      to contribute significantly to the anaesthetic state. Assuming additivity of
      anaesthetic mixtures, our study assessed the effects of corresponding minimum
      alveolar concentrations (MACs) of isoflurane and isoflurane/nitrous oxide on
      thalamic nociceptive signalling. METHODS: Nociceptive response activity (elicited
      by controlled radiant heat stimuli applied to cutaneous receptive fields) of
      single thalamic neurons was compared in rats anaesthetized at approximately 1.1
      and approximately 1.4 MAC isoflurane with that at approximately 1.1 and
      approximately 1.4 MAC isoflurane/nitrous oxide. RESULTS: Under baseline
      anaesthesia ( approximately 0.9 MAC isoflurane), noxious stimulation elicited
      excitatory responses in all neurons (n = 19). These responses were uniformly
      suppressed at approximately 1.1 and approximately 1.4 MAC isoflurane. In
      contrast, at approximately 1.1 and approximately 1.4 MAC isoflurane/nitrous
      oxide, excitatory responses no different to baseline were still present in 64 and
      37% of the neurons, respectively. CONCLUSIONS: These data demonstrate a
      pronounced nitrous oxide-induced response variability. It appears that, with
      respect to thalamic transfer of nociceptive information, the interaction of
      isoflurane and nitrous oxide may not be compatible with the concept of additivity
      and that the antinociceptive potency of nitrous oxide is considerably less than
      previously reported.

PMID- 17210738
TI  - The role of RFamide peptides in feeding.
AB  - In the three decades since FMRFamide was isolated from the clam Macrocallista
      nimbosa, the list of RFamide peptides has been steadily growing. These peptides
      occur widely across the animal kingdom, including five groups of RFamide peptides
      identified in mammals. Although there is tremendous diversity in structure and
      biological activity in the RFamides, the involvement of these peptides in the
      regulation of energy balance and feeding behaviour appears consistently through
      evolution. Even so, questions remain as to whether feeding-related actions
      represent a primary function of the RFamides, especially within mammals. However,
      as we will discuss here, the study of RFamide function is rapidly expanding and
      with it so is our understanding of how these peptides can influence food intake
      directly as well as related aspects of feeding behaviour and energy expenditure.

PMID- 17210739
TI  - Cellular localization of sphingomyelin synthase 2 in the seminiferous epithelium
      of adult rat testes.
AB  - Sphingomyelin synthase 2 (SMS2) is an enzyme that catalyzes the conversion of
      phosphatidylcholine and ceramide to sphingomyelin and diacylglycerol, and it is
      crucial to cellular lipid metabolism. Using the technique of subtraction
      hybridization, we have isolated a full-length cDNA encoding SMS2 from rat testes,
      which shared 93 and 87% identity at the nucleotide level with SMS2 in mice and
      humans respectively. A specific polyclonal antibody was prepared against a 20
      amino acid peptide of NH(2)-FSWPLSWPPGCFKSSCKKYS-COOH near the C-terminus of
      SMS2. Studies by RT-PCR and immunoblotting have shown that the expression of SMS2
      was limited to late round spermatids and elongating spermatids, but it was not
      detected in late elongate spermatids and Sertoli cells. Furthermore, SMS2 was
      shown to associate with the developing acrosome beginning in late round spermatid
      through elongating spermatids (but not late elongate spermatids) and the cell
      membrane in studies using fluorescent microscopy and immunohistochemistry. These
      data were further confirmed by studies using immunogold electron microscopy. The
      expression of SMS2 in the seminiferous epithelium is stage-specific with its
      highest expression detected in the acrosome region in late round spermatids from
      stages VIII-IX, and also in the acrosome in elongating spermatids with diminished
      intensity in stages X-V; however, it was not found in the acrosome in elongate
      spermatids in stages VI-VIII. Collectively, these results suggest that SMS2 may
      play a crucial role in the lipid metabolism in acrosome formation and the plasma
      membrane restructuring from late round spermatids to early elongating spermatids.

PMID- 17210740
TI  - Stimulation of the pituitary-adrenal axis and of adrenocortical steroidogenesis
      ex vivo by administration of di-2-ethylhexyl phthalate to prepubertal male rats.
AB  - Phthalate esters exert deleterious effects on testicular physiology and,
      consequently, on reproduction and fertility. However, little is presently known
      concerning potential adverse effects of these environmental pollutants on the
      hormonal functions of the adrenal gland. Therefore, we have investigated the
      effects of administering to rats of different developmental ages di-2-ethylhexyl
      phthalate (DEHP) on the hypothalamic-pituitary-adrenal axis in vivo, as well as
      on adrenocortical steroidogenesis ex vivo. Oral exposure to DEHP once daily for 4
      days elevated the serum levels of ACTH and corticosterone in rats 20 and 40 days
      of age, but not in adult, 60-day-old animals. Furthermore, primary cultures of
      adrenocortical cells isolated from 20- and 40-day-old rats treated with DEHP
      exhibited an enhanced capacity to produce corticosterone in response to ACTH,
      dibutyryl cAMP, and 22R-hydroxycholesterol, as well as increased ACTH-stimulated
      transport of endogenous cholesterol into mitochondria. Neither DEHP nor its major
      metabolite mono-2-ethylhexyl phthalate altered steroidogenesis in cultures of
      adrenocortical cells isolated from untreated rats. These findings demonstrate
      that in male rats, DEHP exerts an age-dependent influence on the pituitary
      adrenocortical axis in vivo and adrenocortical steroidogenesis ex vivo. Such
      perturbation may be of pathological significance in connection with disorders of
      the hormonal stress response, especially in very young human beings.

PMID- 17210741
TI  - Oestrogen formation and connective tissue growth factor expression in rat
      granulosa cells.
AB  - Ovarian follicular development involves continual remodelling of the
      extracellular matrix (ECM) forming the basement membrane and intercellular
      framework that support granulosa cell (GC) growth and differentiation. Insight
      into the molecular regulation of ovarian ECM remodelling is potentially
      translatable to tissue remodelling elsewhere in the body. We therefore studied
      the link between a gene marker of ECM remodelling (connective tissue growth
      factor (CTGF)) and oestrogen biosynthesis (cytochrome P450(aromatase)
      (P450(arom))) in rat granulosa cells. To determine if a cause-effect interaction
      exists, we used semi-quantitative in situ hybridisation to analyse patterns of
      CTGF and P450(arom) mRNA expression and immunohistochemistry to detect CTGF
      protein localisation throughout follicular development, and tested the actions of
      CTGF on oestrogen biosynthesis and oestradiol on CTGF mRNA expression in isolated
      GC in vitro. CTGF mRNA levels in GC rose gradually through small preantral (SP)
      and small antral (SA) stages of development to a maximum (fivefold higher) in
      large antral (LA) follicles. In preovulatory (PO) follicles, the CTGF mRNA level
      fell to 30% of that in SP follicles. P450(arom) mRNA also increased (threefold in
      LA relative to SP) throughout antral development follicles, but in contrast to
      CTGF continued to increase (12-fold) in PO follicles. In the cumulus oophorus of
      PO follicles, the residual GC CTGF mRNA expression increased with proximity to
      the oocyte, being inversely related to P450(arom). Elsewhere in the follicle
      wall, there was a mural-to-antral gradient of CTGF mRNA expression, again
      inversely related to P450(arom). Immunohistochemistry showed CTGF protein
      localisation broadly followed mRNA expression during follicular development,
      although the protein was also present in the theca interna and ovarian surface
      epithelium. Gradients in CTGF expression across the cumulus oophorus and follicle
      wall were similar to those observed for mRNA with CTGF protein expression being
      greatest in proximity to the oocyte. Treatment of isolated GC from preantral and
      SA follicles with recombinant human CTGF (1-100 ng/ml) did not affect basal or
      FSH-stimulated GC aromatase activity. However, in the absence of FSH, oestradiol
      (10(-7)-10(-5) M) stimulated CTGF mRNA expression up to twofold. Conversely, FSH
      (10 ng/ml) alone reduced CTGF mRNA expression by 40% and combined treatment with
      FSH and oestradiol further suppressed CTGF to 10% of the control value. The
      oestrogen receptor (ER) antagonist, ICI 182 780 blocked the stimulatory and
      inhibitory effects of oestradiol, suggesting a specific ER-mediated mode of
      action on CTGF. Therefore, CTGF gene expression in GC is under local control by
      oestrogen whose effect (positive or negative) is modulated by FSH. This helps
      explain why gene expression of CTGF and P450(arom) diverge in FSH-induced PO
      follicles and has implications for oestrogenic regulation of CTGF formation
      elsewhere in the body.

PMID- 17210742
TI  - Seladin-1 expression in rat adrenal gland: effect of adrenocorticotropic hormone
      treatment.
AB  - Seladin-1 (KIAA0018) gene is the seventh most highlyexpressed gene in the adult
      adrenal gland, along with genes coding for steroidogenic enzymes. The aim of the
      present study was to investigate the localization of the Seladin-1 protein in
      control and ACTH-treated rat adrenal glands and to verify whether Seladin-1 is
      involved in secretion. Immunofluorescence studies revealed that Seladin-1 was
      localized principally in the zona fasciculata, cytoplasm, and nucleus. Expression
      of Seladin-1 was increased by ACTH treatment, in vivo and in culture conditions.
      Subcellular fractionation offasciculata cells showed that Seladin-1 was mainly
      present in the nucleus, membrane, and cytoskeleton fractions and, to a lesser
      extent, in the cytosol. ACTH treatment decreased Seladin-1 expression in the
      cytosol, with a concomitant increase in the nuclear fraction. In the glomerulosa
      and fasciculata cells in culture, ACTH induced a relocalization of Seladin-1 into
      specific nuclear regions. This ACTH-induced relocalization was abrogated by the
      pre-treatment of cells with 75 nM U18666A (an inhibitor of Seladin-1). In
      addition, fasciculata cells exhibited an increase in the basal level of steroid
      secretion when cultured in the presence of U18666A (25 and 75 nM), although ACTH
      induced secretion was decreased. In summary, the present study demonstrates that
      the protein expression of Seladin-1 is more abundant in fasciculata cells than in
      glomerulosa cells and that the ACTH treatment increases both expression and
      nuclear localization of the protein. Results also suggest that depending on its
      cellular localization, the Delta24-reductase activity of Seladin-1 may play a
      major role in steroid secretion in the adrenal gland.

PMID- 17210743
TI  - Effects of dexamethasone on the glucogenic capacity of fetal, pregnant, and non
      pregnant adult sheep.
AB  - Fetal glucocorticoids have an important role in the pre-partum maturation of
      physiological systems essential for neonatal survival such as glucogenesis.
      Consequently, in clinical practice, synthetic glucocorticoids, like
      dexamethasone, are given routinely to pregnant women threatened with pre-term
      delivery to improve the viability of their infants. However, little is known
      about the effects of maternal dexamethasone treatment on the glucogenic capacity
      of either the fetus or mother. This study investigated the effects of
      dexamethasone treatment using a clinically relevant dose and regime on glycogen
      deposition and the activities of glucose-6-phosphatase (G6Pase) and
      phosphoenolpyruvate carboxykinase (PEPCK) in the liver and kidney of pregnant
      ewes and their fetuses, and of non-pregnant ewes. Dexamethasone administration
      increased the glycogen content of both the fetal and adult liver within 36 h of
      beginning treatment. It also increased G6Pase activity in the liver and kidney of
      the fetuses but not of their mothers or the non-pregnant ewes. Neither hepatic
      nor renal PEPCK activity was affected by dexamethasone in any group of animals.
      These changes in glycogen content and G6Pase activity were accompanied by rises
      in the plasma glucose and insulin concentrations and by a fall in the plasma
      cortisol level in the fetus and both groups of adult animals. In addition,
      dexamethasone treatment raised fetal plasma tri-iodothyronine (T(3))
      concentrations and reduced maternal levels of plasma T(3) and thyroxine, but had
      no effect on thyroid hormone concentrations in the non-pregnant ewes. These
      findings show that maternal dexamethasone treatment increases the glucogenic
      capacity of both the mother and fetus and has major implications for glucose
      availability both before and after birth.

PMID- 17210744
TI  - Maternal diet composition alters serum steroid and free fatty acid concentrations
      and vaginal pH in mice.
AB  - We examined the effects of three maternal diets (very high fat (VHF), low fat
      (LF), and control (Purina 5015)) on serum steroids, free fatty acids (FFA), and
      vaginal pH in National Institutes of Health Swiss mice. Females were fed (VHF, n
      = 33; LF, n = 33; 5015, n = 48) from 4 to 16 weeks of age. Following breeding,
      female serum was collected at 0.5 (pre-implantation, early diestrus) or 8.5 (post
      implantation, mid-diestrus) days post-coitus (dpc). The serum concentrations of
      17beta-estradiol, testosterone, progesterone, and FFA were analyzed at both
      collection points, and vaginal pH at 0.5 dpc. Striking differences in steroids
      and FFA were observed at 0.5 dpc among the groups. Estradiol was higher in the
      VHF (14.1 +/- 3.0 pg/ml), compared with LF mice (5.2 +/- 2.3 pg/ml; P< or =
      0.05). In contrast, 0.5 dpc testosterone was lower in the VHF (10.5 +/- 3.0
      pg/ml) versus the LF group (32.7 +/- 8.4 pg/ml; P< or = 0.05). At 8.5 dpc,
      progesterone was higher in the VHF (89.6 +/- 6.7 ng/ml) versus the 5015 group
      (60.1 +/- 4.9 ng/ml; P< or = 0.05). VHF mice had higher FFA concentrations at 0.5
      dpc (1.0 +/- 0.2 mmol/l) than LF and control mice (0.5 +/- 0.1 and 0.6 +/- 0.1
      mmol/l respectively; P< or = 0.05). At 8.5 dpc, VHF females had higher serum FFA
      (0.8 +/- 0.1 mmol/l) than LF and control females (0.4 +/- 0.1 and 0.6 +/- 0.1
      mmol/l; P< or = 0.05). Mean vaginal pH of VHF females (6.41 +/- 0.09) was lower
      than 5015 females (6.76 +/- 0.10; P< or = 0.05). These diet-induced alterations
      in serum steroid and FFA concentrations might affect several reproductive
      processes, including preferential fertilization by one class of sperm over the
      other and sex bias in pre- and post-implantational embryonic development.

PMID- 17210745
TI  - Thyroid hormone receptor beta mutations in the 'hot-spot region' are rare events
      in thyroid carcinomas.
AB  - Thyroid cancer constitutes the most frequent endocrine neoplasia. Targeted
      expression of rearranged during transfection (RET)/papillary thyroid carcinoma
      (PTC) and V600E V-raf murine sarcoma viral oncogene homolog B1 (BRAF) to the
      thyroid glands of transgenic mice results in tumours similar to those of human
      PTC, providing evidence for the involvement of these oncogenes in PTC. Kato et
      al. developed a mouse model that mimics the full spectrum of the human follicular
      form of thyroid cancer (FTC). FTC rapidly develops in these mice through
      introduction of the thyroid hormone receptor beta (THRB)(PV) mutant on the
      background of the inactivated THRB wt locus. Our aim was to verify if, in the
      context of human follicular thyroid carcinogenesis, THRB acted as a tumour
      suppressor gene. We screened for mutations of the THRB gene in the hot-spot
      region, spanning exons 7-10, in 51 thyroid tumours and six thyroid cancer cell
      lines by PCR and direct sequencing. We did not find mutations in any of the
      tumours or cell lines analysed. Our findings suggest that, in contrast to the
      findings on the THRB-mutant transgenic mice, THRB gene mutations are not a
      relevant mechanism for human thyroid carcinogenesis.

PMID- 17210746
TI  - Maternal nutrient restriction in early pregnancy programs hepatic mRNA expression
      of growth-related genes and liver size in adult male sheep.
AB  - The liver is a major metabolic and endocrine organ of critical importance in the
      regulation of growth and metabolism. Its function is determined by a complex
      interaction of nutritionally regulated counter-regulatory hormones. The extent to
      which hepatic endocrine sensitivity can be programed in utero and whether the
      resultant adaptations persist into adulthood is unknown and was therefore the
      subject of this study. Young adult male sheep born to mothers that were fed
      either a control diet (i.e.100% of total live weight-maintenance requirements)
      throughout gestation or 50% of that intake (i.e. nutrient restricted (NR)) from 0
      to 95 days gestation and thereafter 100% of requirements (taking into account
      increasing fetal mass) were entered into the study. All mothers gave birth
      normally at term, the singleton offspring were weaned at 16 weeks, and then
      reared at pasture until 3 years of age when their livers were sampled. NR
      offspring were of similar birth and body weights at 3 years of age when they had
      disproportionately smaller livers than controls. The abundance of mRNA for GH,
      prolactin, and IGF-II receptors, plus hepatocyte growth factor and suppressor of
      cytokine signaling-3 were all lower in livers of NR offspring. In contrast, the
      abundance of the mitochondrial protein voltage-dependent anion channel and the
      pro-apoptotic factor Bax were up regulated relative to controls. In conclusion,
      maternal nutrient restriction in early gestation results in adult offspring with
      smaller livers. This may be mediated by alterations in both hepatic mitogenic and
      apoptotic factors.

PMID- 17210747
TI  - Male congenital hypothyroid Pax8-/- mice are infertile despite adequate treatment
      with thyroid hormone.
AB  - Severe forms of congenital hypothyroidism lead to serious clinical symptoms if
      thyroid hormone replacement therapy is not instituted immediately after birth. In
      this study, Pax8(-/-) mice that are born without a thyroid gland were used as an
      animal model to study the consequences of congenital hypothyroidism. As expected,
      adequate treatment of these animals with thyroxine restored the general deficits
      of congenital hypothyroidism; however, Pax8-deficient male mice were infertile.
      We report here that in these mice, the efferent ducts and epididymides are either
      absent or the efferent ducts exhibit a reduced lumen and extensive connective
      tissue, which appears to impair testicular drainage and subsequently leads to
      complete absence of spermatozoa from the epididymis. The results suggest that,
      starting with the onset of pubertal testicular fluid secretion, a backpressure is
      created in the testis by the absence of efferent ducts or constriction of their
      tubule lumen when present. This subsequently leads to secondary disorganization
      of the seminiferous epithelium that increases with age, resulting in mixed
      atrophy of the testis in the adult. Serum testosterone levels as well as mRNA
      expression of anterior pituitary hormones are in the normal range, indicating
      that the observed infertility is not due to hormonal imbalance, but rather to a
      developmental defect of the efferent ducts. The demonstration of Pax8 expression
      in the epithelia of the epididymis and the efferent ducts suggests a direct
      morphogenic role of Pax8 in the development of these organs. It remains to be
      elucidated whether congenital hypothyroid male patients with mutations in the
      Pax8 gene are similarly affected.

PMID- 17210748
TI  - Triiodothyronine modulates the expression of aquaporin-8 in rat liver
      mitochondria.
AB  - The recent identification of aquaporin-8 (AQP8), an aquaporin (AQP) channel
      permeable to water and ammonia, in the inner membrane (IMM) of rat liver
      mitochondria suggested a role for such AQP in the hydration state and the
      metabolic function of mitochondria. Since thyroid hormone triiodothyronine (T3)
      is known to modulate both the shape and the metabolic activities of liver
      mitochondria, it was interesting to investigate the expression and distribution
      of AQP8 as well as the osmotic water permeability of the IMM in liver
      mitochondria from rats in different thyroid states. By semi-quantitative reverse
      transcriptase (RT)-PCR, when compared with the euthyroid counterpart, the levels
      of hepatic AQP8 mRNA significantly increased in the hypothyroid state, whereas
      they were strongly decreased after administration of T3. A similar pattern was
      seen at the protein level by immunoblotting mitochondrial membranes. The
      upregulation of mitochondrial AQP8 in the hypothyroid liver was confirmed by
      immunogold electron microscopy. Stopped-flow light scattering with IMM vesicles
      showed no significant differences in terms of osmotic water permeability among
      the IMMs in the various thyroid states. Overall, our data indicate that the T3
      modulation of the AQP8 gene is a rapid downregulation of transcription.
      Modulation of hepatic AQP8 expression may be relevant to the regulation of
      mitochondrial metabolism by thyroid hormones.

PMID- 17210750
TI  - Effect of mechanical loading on insulin-like growth factor-I gene expression in
      rat tibia.
AB  - Mechanical loading plays an essential role in maintaining skeletal integrity.
      Mechanical stimulation leads to increased bone formation. However, the cellular
      and molecular mechanisms that are involved in the translation of mechanical
      stimuli into bone formation, are not completely understood. Growth factors and
      osteocytes, which act as mechanosensors, play a key role during the bone
      formation after mechanical stimulation. The aim of this study was to characterize
      the role of IGF-I in the translation of mechanical stimuli into bone formation
      locally in rat tibiae. Fifteen female Wistar rats were randomly assigned to three
      groups (n = 5): load, sham-loaded, and control. The four-point bending model of
      Forwood and Turner was used to induce a single period of mechanical loading on
      the tibia shaft. The effects of mechanical loading on IGF-I mRNA expression were
      determined with non-radioactive in situ hybridization on decalcified tibiae
      sections, 6 h after the loading session. Endogenous IGF-I mRNA was expressed in
      trabecular and cortical osteoblasts, some trabecular and sub-endocortical
      osteocytes, intracortical endothelial cells of blood vessels, and periosteum.
      Megakaryocytes, macrophages, and myeloid cells also expressed IGF-I mRNA. In the
      growth plate, IGF-I mRNA was located in proliferative and hypertrophic
      chondrocytes. Mechanical loading did not affect the IGF-I mRNA expression in
      osteoblasts, bone marrow cells, and chondrocytes, but the osteocytes at the
      endosteal side of the shaft showed a twofold increase of IGF-I mRNA expression.
      The proportion of IGF-I mRNA positive osteocytes in loaded tibiae was 29.3 +/-
      12.9% (mean +/- s.d.; n = 5), whereas sham-loaded and contra-lateral control
      tibiae exhibited 16.7 +/- 4.4% (n = 5) and 14.7 +/- 4.2% (n = 10) respectively (P
      < 0.05). Lamellar bone formation after a single mechanical loading session was
      observed at the endosteal side of the shaft. In conclusion, a single loading
      session results in a twofold up-regulation of IGF-I mRNA synthesis in osteocytes
      which are present in multiple layers extending into the cortical bone of
      mechanically stimulated tibia shaft 6 h after loading. This supports the
      hypothesis that IGF-I, which is located in osteocytes, is involved in the
      translation of mechanical stimuli into bone formation.

PMID- 17210749
TI  - Sexual dimorphism in thyroid function and type 1 iodothyronine deiodinase
      activity in pre-pubertal and adult rats.
AB  - Iodothyronine deiodinase activities are regulated by sex steroids; however, the
      mechanisms underlying the reported sexual dimorphism are poorly defined. In the
      present report, we aimed to investigate whether type 1 deiodinase (D1) sexual
      dimorphism exists early in sexual development by studying pre-pubertal male (Pm)
      and female (Pf) rats, as well as adult controls (C) and gonadectomized male and
      females rats. Adult male Wistar rats were studied 21 days after orchiectomy
      (Tex), and adult females were studied 21 days after ovariectomy (Ovx), and after
      estradiol benzoate (Eb) replacement. Serum total triiodothyronine (T3) was higher
      in pre-pubertal (P) rats than in the matching adults, with no difference between
      genders, although in adult males T3 was significantly lower than in females.
      There were no sex or age differences in serum total T4. Serum TSH in pre-pubertal
      (P) rats was within the adult female range, and both were significantly lower
      than in adult males. D1 activity in liver was greater in Pm than in Pf. In adult
      females, liver D1 activity was lower, while in adult males it was higher than in
      P rats. The same pattern of D1 activity was found in kidney. In thyroid and
      pituitary, D1 activity was similar in Pm, Pf, and adult females, which were all
      significantly lower than in the adult male. There were no differences in serum T3
      and T4 between C and Tex males, but serum TSH was significantly decreased in Tex
      rats. Hepatic and renal D1 activities were lower in Tex than in C, but no changes
      were detected in thyroid and pituitary. In Ovx females, T3 was significantly
      lower than in the C group. Serum T4 was significantly decreased by estradiol
      replacement therapy in Ovx rats, in both doses used, whereas TSH was unchanged.
      Eb replacement increased liver and thyroid D1 activity, but in the kidney, only
      the highest estradiol dose promoted a significant D1 increase. In conclusion, in
      males, hepatic and renal D1 activity appears to be significantly influenced by
      gonadal hormones, in contrast to females, in which only exogenous Eb treatment
      stimulated D1 activity. The comparison between pre-pubertal and adult rats
      suggests that serum T3 is not the main regulator of D1 activity, and other
      factors, besides T3 and gonadal hormones, can modulate D1 activity during murine
      maturation.

PMID- 17210751
TI  - Regulation of human insulin, IGF-I, and multidrug resistance protein 2 promoter
      activity by hepatocyte nuclear factor (HNF)-1beta and HNF-1alpha and the
      abnormality of HNF-1beta mutants.
AB  - Mutations in hepatocyte nuclear factor-1beta (HNF-1beta) lead to type 5 maturity
      onset diabetes of the young (MODY5). Moreover, mutations in the HNF-1beta gene
      might cause multiorgan abnormalities including renal diseases, genital
      malformations, and abnormal liver function. The objective of this study was to
      investigate the molecular mechanism of diabetes mellitus, intrauterine growth
      retardation, and cholestasis observed in MODY5 patients. We analyzed the
      transactivity of wild-type and three mutant HNF-1beta on native human insulin,
      IGF-I, and multidrug resistance protein 2 (MRP2) promoters in combination with
      HNF-1alpha, using a reporter-assay system in transiently transfected mammalian
      cells. In the human insulin gene promoter, we found that the cooperation of HNF
      1alpha and HNF-1beta is prominent. Absence of this cooperation was observed in
      all of the HNF-1beta mutants. In the human IGF-I and MRP2 promoters, we found
      that the HNF-1beta His153Asn (H153N) mutant had a mutant-specific repressive
      effect on both HNF-1alpha and wild-type HNF-1beta transactivity. Absence of the
      cooperation of HNF-1beta mutants with HNF-1alpha in the human insulin gene
      promoter might be one cause of defective insulin secretion. The H153N mutant
      specific repression of HNF-1alpha and HNF-1beta transactivity in human IGF-I and
      MRP2 promoters might explain the case-specific clinical features of growth
      retardation and cholestasis observed only in early infancy. We found differential
      property of HNF-1alpha/HNF-1beta activity and the effect of HNF-1beta mutants by
      the promoters. We consider that analyses of HNF-1beta mutants on the intended
      human native promoters in combination with HNF-1alpha may be useful in
      investigating the molecular mechanisms of the various features in MODY5.

PMID- 17210752
TI  - Bidirectional regulation of upstream IGF-I/insulin receptor signaling and
      downstream FOXO1 in cardiomyocytes.
AB  - Signaling pathways of IGF-I and insulin receptors play important roles in the
      regulation of myocardial function. FOXO1 is a member of the forkhead
      transcriptional factor family, but how insulin and IGF-I receptor signaling
      regulate FOXO1 in cardiomyocytes is not well understood. This study was carried
      out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in
      cardiomyocytes. In cardiomyocytes, activation of IGF-I receptor and insulin
      receptor lead to rapid phosphorylation of FOXO1. Inhibition of
      phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and
      IGF-I on FOXO1 phosphorylation. Prolonged incubation with IGF-I increased
      ubiquitination of FOXO1 and down-regulated the abundance of FOXO1 proteins, which
      suggested that IGF-I might modulate FOXO1 degradation. To explore whether FOXO1
      could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was
      overexpressed in cardiomyocytes. The abundance of insulin receptor and IGF-I
      receptor was significantly upregulated in the cells overexpressing active FOXO1,
      accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation.
      Interestingly, overexpression of constitutively active FOXO1 also led to
      activation of MEK and Akt phosphorylation. IGF-I-stimulated MEK and Akt
      phosphorylation were augmented byoverexpression of constitutively active FOXO1.
      These findings indicate bidirectional regulation of insulin/IGF-I receptor
      signaling and FOXO1 in cardiomyocytes. FOXO1 may provide feedback control through
      upregulation of insulin and IGF-I receptor signaling.

PMID- 17210753
TI  - Insulin secretory actions of extracts of Asparagus racemosus root in perfused
      pancreas, isolated islets and clonal pancreatic beta-cells.
AB  - Asparagus racemosus root has previously been reported to reduce blood glucose in
      rats and rabbits. In the present study, the effects of the ethanol extract and
      five partition fractions of the root of A. racemosus were evaluated on insulin
      secretion together with exploration of their mechanisms of action. The ethanol
      extract and each of the hexane, chloroform and ethyl acetate partition fractions
      concentration-dependently stimulated insulin secretion in isolated perfused rat
      pancreas, isolated rat islet cells and clonal beta-cells. The stimulatory effects
      of the ethanol extract, hexane, chloroform and ethyl acetate partition fractions
      were potentiated by glucose, 3-isobutyl-1-methyl xanthine IBMX, tolbutamide and
      depolarizing concentration of KCl. Inhibition of A. racemosus-induced insulin
      release was observed with diazoxide and verapamil. Ethanol extract and five
      fractions increased intracellular Ca(2+), consistent with the observed abolition
      of insulin secretory effects under Ca(2+) -free conditions. These findings reveal
      that constituents of A. racemosus root extracts have wide-ranging stimulatory
      effects on physiological insulinotropic pathways. Future work assessing the use
      of this plant as a source of active components may provide new opportunities for
      diabetes therapy.

PMID- 17210754
TI  - Interleukin-1beta and inducible form of nitric oxide synthase expression in early
      syngeneic islet transplantation.
AB  - Islets are particularly vulnerable in the initial days after transplantation when
      cell death results in the loss of more than half of the transplanted islet
      tissue. To determine whether a non-specific inflammation at the grafted site
      mediated by the local expression of inflammatory cytokines could play a role on
      the initial damage to transplanted islets, we studied the expressions of
      interleukin-1beta (IL-1beta) and inducible form of nitric oxide synthase (iNOS)
      after syngeneic islet transplantation. Insulin-treated streptozotocin-diabetic
      Lewis rats were syngeneically transplanted with 500 islets. Grafts were harvested
      1, 3, or 7 days after transplantation, and the expressions of IL-1beta and iNOS
      genes were determined by RT-PCR. IL-1beta and iNOS mRNAs were detected in islets
      immediately after isolation, and were upregulated after transplantation. IL-1beta
      mRNA was ninefold increased on day 1, was still sevenfold increased on day 3
      after transplantation, and declined towards pretransplantation levels on day 7.
      iNOS mRNA showed a similar pattern of expression to that of IL-1beta: on days 1
      and 3 after transplantation it was 14-and 4-fold higher respectively than in
      freshly isolated islets. In addition, IL-1beta and iNOS were identified in islet
      grafts and found to be produced mainly by CD68-positive macrophages. A low number
      of IL-1beta- and iNOS-positive but CD68-negative cells were also identified
      suggesting that other cell types, in addition to macrophages, were involved in
      the expression of IL-1beta and NO production in islet grafts. The finding of
      increased IL-1beta and iNOS gene expressions in the initial days after islet
      transplantation and the presence of IL-beta and iNOS proteins in the graft
      confirmed the presence of an early non-specific inflammatory response after islet
      transplantation. Overall, the data suggest that IL-1beta plays a role in the
      extensive beta-cell death found in the initial days after islet transplantation.

PMID- 17210755
TI  - Distinct glucose-dependent stress responses revealed by translational profiling
      in pancreatic beta-cells.
AB  - In pancreatic beta-cells, following an acute (within 1 h) increase in glucose
      concentration, there are rapid changes in the expression of a large subset of
      proteins. The change in the expression of many of these proteins is mediated by a
      post-transcriptional mechanism through either increases or decreases in the rate
      of translation from pre-existing transcripts. These proteins, whose synthesis is
      rapidly up- or down-regulated in response to glucose, are likely important in
      mounting the correct response to changes in plasma glucose concentrations.
      However, the vast majority of these proteins remain unidentified. Therefore, in
      order to identify these proteins, we analysed changes in the levels of mRNAs
      associated with polysomes (i.e. actively translating mRNAs) isolated from mouse
      insulinoma 6 cells incubated at either 0.5 or 20 mM glucose for 1 h. Changes in
      the levels of polysomal mRNAs in response to glucose were analysed using
      affymetrix oligonucleotide microarrays (translational profiling). This work
      revealed that, in response to a change in glucose concentration, the abundance of
      313 transcripts associated with polysomes changed by more than 1.5-fold, of which
      the abundance of 37 changed by more than twofold. The majority of these
      transcripts encoded proteins associated with metabolism or gene expression. More
      detailed analysis showed that a number of mRNAs encoding proteins associated with
      the induction of oxidative stress, including thioredoxin-2 and thioredoxin
      interacting protein were rapidly redistributed onto heavier polysomes at high
      glucose concentration, indicating an increase in their expression. At low glucose
      concentration, when the general rate of protein synthesis is low, a number of
      mRNAs encoding integrated stress response proteins, including ATF4 and CHOP10,
      associate with heavier polysomes, indicating that their expression is up
      regulated. In conclusion, translational profiling has revealed that, at either
      low or at high glucose concentration, beta-cells rapidly increase the synthesis
      of a specific subset of proteins that are likely important in maintaining beta
      cell integrity and survival during conditions of nutritional stress.

PMID- 17210756
TI  - Protein kinase C activation increases endothelial nitric oxide release in
      mesenteric arteries from orchidectomized rats.
AB  - The aim of the present study was to assess the effect of endogenous male sex
      hormones on endothelial nitric oxide synthase (eNOS) expression, release and
      function of the endothelial nitric oxide (NO), as well as to assess the
      regulatory action of protein kinase C (PKC) on acetylcholine (ACh)-induced
      endothelial NO release. For this purpose, superior mesenteric arteries from
      control and orchidectomized male Sprague-Dawley rats were used. eNOS expression
      and basal-and ACh-induced NO release were similar in arteries from both groups of
      rats. Orchidectomy decreased the vasodilator effect induced by ACh but did not
      alter that induced by sodium nitroprusside (SNP). The superoxide anion scavenger,
      superoxide dismutase (SOD), or the membrane-permeable mimetic of SOD, tempol,
      only enhanced ACh-induced relaxation in arteries from orchidectomized rats. ACh
      induced TXA(2) formation was higher in arteries from orchidectomized than from
      control rats. Neither the PKC activator, phorbol 12,13-dibutyrate (PDBu), nor the
      non-selective PKC inhibitor, calphostin C, modified basal- or ACh-induced NO
      release in arteries from control rats. In arteries from orchidectomized rats,
      basal- and ACh-induced endothelial NO release were increased by PDBu but
      decreased by calphostin C. Both Go6976, a PKC inhibitor that is partially
      selective for conventional PKC isoforms, as well as PKCzeta pseudosubstrate
      inhibitor (PKCzeta-PI) decreased both basal- and ACh-induced NO release in
      arteries from orchidectomized rats. Neither PDBu nor calphostin C modified the
      vasodilator response induced by ACh in arteries from control rats. In segments
      from orchidectomized rats, PDBu enhanced the ACh-induced response, but this
      response was not modified by calphostin C, Go6976 or PKCzeta-PI. The vasodilator
      response induced by SNP was not altered by the PKC activators or inhibitors in
      any artery from either group. These results show that endogenous male sex hormone
      deprivation does not affect the eNOS expression or the endothelial NO release
      induced by ACh, but does decrease the vasodilator action of ACh, by increasing NO
      metabolism and TXA(2) formation. In addition, PKC seems to modulate eNOS activity
      only in mesenteric arteries from orchidectomized rats, in which conventional and
      PKCzeta isoforms are involved in the positive regulation of eNOS.

PMID- 17210757
TI  - Autocrine proliferative effect of ghrelin on leukemic HL-60 and THP-1 cells.
AB  - Ghrelin is a 28 amino acid peptide hormone that is mainly produced by the
      stomach, but also by several tissues and tumors. Ghrelin is octanoylated on the
      Ser(3), but is also detected as a des-acylated form. Only the acylated ghrelin
      activates the GH secretagogue receptor (GHS-R) type 1a to stimulate GH release,
      and regulate food intake and energy metabolism. For the first time, we report
      that ghrelin and des-acyl ghrelin are present in human promyelocytic HL-60,
      monocytic THP-1 and lymphoblastic SupT1 cell lines. The human leukemic cell lines
      did not express the functional GHS-R 1a, whereas they expressed GHS-R 1b, a
      truncated variant of the receptor. Leukemic cell proliferation was not modified
      by the addition of octanoylated or des-acyl ghrelins. However, THP-1 and HL-60
      cell proliferations were inhibited by SB801, an antibody directed against the N
      terminal octanoylated portion of ghrelin, suggesting that octanoylated ghrelin
      stimulates cell proliferation via an autocrine pathway involving an as yet
      unidentified ghrelin receptor. Both octanoylated and des-acyl ghrelins did not
      alter the basal adenylate cyclase activity. Treatments of THP-1 and SupT1 cells
      by both octanoylated and des-acyl ghrelins did not modify the adenylate cyclase
      activity in response to vasoactive intestinal peptide, suggesting that ghrelin is
      unlikely to modulate the anti-inflammatory and differentiating properties of
      vasoactive intestinal peptide.

PMID- 17210758
TI  - N-Acetylcysteine and alpha-cyano-4-hydroxycinnamic acid alter protein kinase C
      (PKC)-delta and PKC-zeta and diminish dysmorphogenesis in rat embryos cultured
      with high glucose in vitro.
AB  - Malformations and growth disturbances are two- to threefold more common in
      infants of diabetic mothers than in offspring of non-diabetic pregnancy. Several
      suggestions have emerged to explain the reasons for diabetic embryopathy,
      including enhanced mitochondrial production of reactive oxygen species leading to
      altered activation of protein kinase C. This study aimed to evaluate the effect
      of alpha-cyano-4-hydroxycinnamic acid (CHC) and N-acetylcysteine (NAC) addition
      on morphology and activity of protein kinase C-delta and protein kinase C-zeta in
      rat embryos exposed to a high glucose concentration in vitro. Day 9 embryos from
      normal rats were cultured in 10 or 30 mM glucose concentrations with or without
      supplementation of CHC, NAC, or protein kinase C inhibitors specific for protein
      kinase C-delta and protein kinase C-zeta. Embryos were evaluated for
      malformations, crown rump length, and somite number. Protein kinase C-delta and
      protein kinase C-zeta activities were estimated by western blot by separating
      membranous and cytosolic fractions of the embryo. We found increased
      malformations and growth retardation in embryos cultured in high versus low
      glucose concentrations. These abnormalities were diminished when CHC and NAC or
      specific protein kinase C-inhibitors were added to the culture medium. The
      activities of embryonic protein kinase C-delta and protein kinase C-zeta were
      increased in the high glucose environment after 24-h culture, but were normalized
      by the addition of CHC and NAC as well as respective inhibitor to the culture
      medium. These findings suggest that mitochondrial overproduction of reactive
      oxygen species is involved in diabetic embryopathy. Furthermore, such
      overproduction may affect embryonic development, at least partly, by enhancing
      the activities of protein kinase C-delta and protein kinase C-zeta.

PMID- 17210759
TI  - Cell-specific expression of X-linked inhibitor of apoptosis in the anterior
      pituitary of streptozotocin-induced diabetic rats.
AB  - Cell death is increased in the anterior pituitary of poorly controlled diabetic
      rats, but anti-apoptotic mechanisms are also activated. We hypothesized that
      specific cell types are selectively protected against diabetes-induced cell
      death. To determine when anti-apoptotic mechanisms are activated, streptozotocin
      induced diabetic rats were killed after 1, 4, 6 and 8 weeks of evolution.
      Anterior pituitaries were processed for western blot analysis to determine
      changes in the intrinsic cell death pathway and upstream kinases involved in cell
      protection mechanisms. An increase in cell death was detected by ELISA at 4 weeks
      of diabetes. TUNEL labelling demonstrated that this corresponded to death of
      primarily lactotrophs, a few somatotrophs, and no thyrotrophs, corticotrophs or
      gonadotrophs. Levels of phosphorylated (p) Akt were increased at 1 week of
      diabetes, while pERK1/2 levels increased at 4 weeks and pJNK at 6 weeks.
      Activation of caspase 3 decreased and anti-apoptotic members of the Bcl-2 protein
      family increased as early as 1 week after diabetes onset. These changes were
      coincident with increased IGF-I receptor levels. Levels of X-linked inhibitor of
      apoptosis protein (XIAP) increased significantly after 6 weeks of diabetes, as
      did activation of nuclear factor (NF)kappaB. Double immunohistochemistry
      indicated that XIAP was expressed in less than 1% of lactotrophs and
      gonadotrophs, approximately 50% of somatotrophs and more than 90% of
      corticotrophs and thyrotrophs. These results suggest that some cell survival
      mechanisms are rapidly activated in the anterior pituitary, even before increased
      cell death can be detected, while others are more delayed. Furthermore, both
      pituitary cell death and expression of protective mechanisms such as XIAP are
      cell-type specific.

PMID- 17210760
TI  - The regulation of stearoyl-CoA desaturase gene expression is tissue specific in
      chickens.
AB  - Emerging evidence suggests a potential role of stearoyl-CoA desaturase (SCD)-1 in
      the control of body weight and energy homeostasis. The present study was
      conducted to investigate the effects of several energy balance-related factors
      (leptin, cerulenin, food deprivation, genotype, and gender) on SCD gene
      expression in chickens. In experiment 1, 6-week-old female and male broiler
      chickens were used. In experiment 2, two groups of 3-week-old broiler chickens
      were continuously infused with recombinant chicken leptin (8 micro g/kg/h) or
      vehicle for 6 h. In experiment 3, two groups of 2-week-old broiler chickens
      received i.v. injections of cerulenin (15 mg/kg) or vehicle. In experiment 4, two
      broiler chicken lines (fat and lean) were submitted to two nutritional states
      (food deprivation for 16 or 24 h and feeding ad libitum). At the end of each
      experiment, tissues were collected for analyzing SCD gene expression. Data from
      experiment 1 showed that SCD is ubiquitously expressed in chicken tissues with
      highest levels in the proventriculus followed by the ovary, hypothalamus, kidney,
      liver, and adipose tissue in female, and hypothalamus, leg muscle, pancreas,
      liver, and adipose tissue in male. Female chickens exhibited significantly higher
      SCD mRNA levels in kidney, breast muscle, proventriculus, and intestine than male
      chickens. However, hypothalamic SCD gene expression was higher in male than in
      female (P < 0.05). Leptin increased SCD gene expression in chicken liver (P <
      0.05), whereas cerulenin decreased SCD mRNA levels in muscle. Both leptin and
      cerulenin significantly reduced food intake (P < 0.05). Food deprivation for
      either 16 or 24 h decreased the hepatic SCD gene expression in fat line and lean
      line chickens compared with their fed counterparts (P < 0.05). The hypothalamic
      SCD mRNA levels were decreased in both lines only after 24 h of food deprivation
      (P < 0.05). In conclusion, SCD is ubiquitously expressed in chickens and it is
      regulated by leptin, cerulenin, nutritional state, and gender in a tissue
      specific manner.

PMID- 17210761
TI  - Developmental expression of cell cycle regulators in the baboon fetal adrenal
      gland.
AB  - Although the human and the nonhuman primate fetal adrenal glands undergo a highly
      unique pattern of cortical zone-specific intrauterine growth and development,
      studies of the regulatory components of the cell cycle responsible for this
      growth have not been conducted. Therefore, the present study determined
      expression of the cell cycle regulators, cyclin D1 and cyclin E, and their cyclin
      dependent kinases, Cdk2, Cdk4, and Cdk6, and Ki67 a marker of cell proliferation
      within the baboon fetal adrenal cortex during advancing stages of gestation.
      Fetal adrenal glands were obtained on days 60 (early), 100 (mid), and 160-170
      (late) of gestation (term = 184 days). Mean (+/- s.e.) cyclin D1 mRNA levels,
      determined by RT-PCR and expressed relative to 18S rRNA, were similar at early
      (0.85 +/- 0.09) and mid (1.04 +/- 0.08) gestation, then decreased (P < 0.001,
      ANOVA) approximately 50% by late gestation (0.57 +/- 0.04). Cyclin E mRNA levels
      were also similar at early (2.03 +/- 0.07) and mid (1.63 +/- 0.31) gestation, and
      decreased by 70% (P < 0.001) in late gestation (0.53 +/- 0.09). Coinciding with
      the decrease in cyclin D1 and cyclin E, the percentage of Ki67 positive cells in
      the definitive zone decreased twofold (P < 0.01) between mid (28.2 +/- 3.6) and
      late (13.8 +/- 1.7) gestation. The cyclin D1 and cyclin E proteins, determined by
      immunocytochemistry, were expressed at high levels in the definitive zone of
      baboon fetal adrenal gland, where they decreased between mid- and late gestation.
      In contrast, immunocytochemical expression of the functionally important
      steroidogenic enzyme Delta(5)-3beta-hydroxysteroid dehydrogenase (3beta-HSD)
      became abundant in the definitive and transitional zones with advancing
      pregnancy. However, fetal adrenal Cdk2, Cdk4, and Cdk6 mRNA levels and protein
      immunoexpression were similar in the baboon fetal adrenal at early-, mid-, and
      late gestation. In summary, expression of cyclin D1, cyclin E, and Ki67
      decreased, while 3beta-HSD expression increased, in the fetal adrenal cortex,
      particularly in the definitive zone, between mid- and late-baboon gestation. We
      propose that a developmental decline in cellular proliferation permits functional
      differentiation of fetal adrenal cortical cells, leading to increased production
      of steroid hormones important for placental estrogen synthesis and maturation of
      organ systems within the developing fetus.

PMID- 17210762
TI  - Differential regulation of cystic fibrosis transmembrane conductance regulator
      and Na+,K+ -ATPase in gills of striped bass, Morone saxatilis: effect of salinity
      and hormones.
AB  - Effects of salinity and hormones on cystic fibrosis transmembrane conductance
      regulator (CFTR) and alpha-subunit Na(+),K(+) -ATPase (alpha-NKA) mRNA (analysed
      by semi-quantitative PCR) and protein expression (analysed by western blotting
      and immunocytochemistry) were investigated in gills of striped bass. Freshwater
      (FW) to seawater (SW) transfer induced a disturbance in serum [Na(+)]. Gill CFTR
      protein, mRNA level and Na(+),K(+) -ATPase activity were unaffected by SW
      transfer, whereas alpha-NKA mRNA increased after transfer. CFTR immunoreactivity
      was observed in large cells in FW and SW gill filaments at equal intensity.
      Cortisol decreased serum [Na(+)] in FW fish, but had no effect on gill Na(+),K(+)
      -ATPase activity, alpha-NKA and CFTR mRNA levels. Incubation of gill tissue with
      cortisol (24 h, >0.01 micro g/ml) and epidermal growth factor (EGF 10 micro g/ml)
      decreased CFTR mRNA levels relative to pre-incubation and control levels. CFTR
      expression was unaffected by IGF-I (10 micro g/ml). alpha-NKA mRNA levels
      decreased by 50% after 24 h control incubation; it was slightly stimulated by
      cortisol and unaffected by IGF-I and EGF. In isolated gill cells, phosphorylation
      of extracellular-regulated kinase (ERK) 1/2 was stimulated by EGF but not
      affected by IGF-I. This study is the first to report a branchial EGF response and
      to demonstrate a functional ERK 1/2 pathway in the teleost gill. In conclusion,
      CFTR and Na(+),K(+) -ATPase are differentially regulated by salinity and hormones
      in gills of striped bass, despite the putative involvement of both in salt
      excretion.

PMID- 17210763
TI  - Phosphorylated acidic serine-aspartate-rich MEPE-associated motif peptide from
      matrix extracellular phosphoglycoprotein inhibits phosphate regulating gene with
      homologies to endopeptidases on the X-chromosome enzyme activity.
AB  - Inactivating PHEX (phosphate regulating gene with homologies to endopeptidases on
      the X chromosome) mutations cause X-linked hypophosphatemia in humans and mice
      (Hyp) through overproduction of fibroblast growth factor 23 (FGF23) a
      phosphaturic factor, by osteocytes. Matrix extracellular phosphoglycoprotein
      (MEPE) is also elevated in Hyp and other hypophosphatemic disorders. In addition,
      the administration of an ASARM (acidic serine-aspartate rich MEPE-associated
      motif) peptide derived from MEPE causes phosphaturia and inhibits bone
      mineralization in mice, suggesting that MEPE also plays a role in phosphate
      homeostasis. Since recent studies found that MEPE binds specifically to PHEX in
      vitro, we tested the effect of recombinant-MEPE and its ASARM peptide on PHEX
      enzyme activity in vitro and FGF23 expression in bone marrow stromal cell
      cultures ex vivo. We found that both recombinant MEPE and synthetic
      phosphorylated ASARM peptide (ASARM-PO(4)) inhibit PHEX enzyme activities in an
      in vitro fluorescent-quenched PHEX enzyme activity assay. The ASARM-PO(4) peptide
      inhibits PHEX enzyme activity in a dose-dependent manner with a K(i) of 128 nM
      and V(max-i) of 100%. Recombinant MEPE also inhibits PHEX activity (K(i) = 2 nM
      and V(max-i) = 26%). Long-term bone marrow stromal cell cultures supplemented
      with 10 microM ASARM-PO(4) peptide resulted in significant elevation of FGF23
      transcripts and inhibition of mineralization. These findings suggest that MEPE
      inhibits mineralization and PHEX activity and leads to increased FGF23
      production. The resulting coordination of mineralization and release of a
      phosphaturic factor by MEPE may serve a physiological role in regulating systemic
      phosphate homeostasis to meet the needs for bone mineralization.

PMID- 17210764
TI  - High-level telithromycin resistance in a clinical isolate of Streptococcus
      pneumoniae.
AB  - A rare clinical isolate of Streptococcus pneumoniae, highly resistant to
      telithromycin, contained erm(B) with a truncated leader peptide and a mutant
      ribosomal protein L4. By transformation of susceptible strains, this study shows
      that high-level telithromycin resistance is conferred by erm(B), wild type or
      mutant, in combination with a (69)GTG(71)-to-TPS mutation in ribosomal protein
      L4.

PMID- 17210765
TI  - Antimicrobial activities of ceragenins against clinical isolates of resistant
      Staphylococcus aureus.
AB  - The rise in the rates of glycopeptide resistance among Staphylococcus aureus
      isolates is concerning and underscores the need for the development of novel
      potent compounds. Ceragenins CSA-8 and CSA-13, cationic steroid molecules that
      mimic endogenous antimicrobial peptides, have previously been demonstrated to
      possess broad-spectrum activities against multidrug-resistant bacteria. We
      examined the activities of CSA-8 and CSA-13 against clinical isolates of
      vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate
      S. aureus (hVISA), as well as vancomycin-resistant S. aureus (VRSA) and compared
      them to those of daptomycin, linezolid, and vancomycin by susceptibility testing
      and killing curve analysis. We also examined CSA-13 for its concentration
      dependent activity, inoculum effect, postantibiotic effect (PAE), and synergy in
      combination with various antimicrobials. Overall, the MICs and minimal
      bactericidal concentrations of CSA-13 were fourfold lower than those of CSA-8.
      Time-kill curve analysis of the VRSA, VISA, and hVISA clinical isolates
      demonstrated concentration-dependent bactericidal killing. An inoculum effect was
      also observed when a higher starting bacterial density was used, with the time
      required to achieve 99.9% killing reaching 1 h with a 6-log10-CFU/ml starting
      inoculum, whereas it was>or=24 h with a 8- to 9-log10-CFU/ml starting inoculum
      with 10x the MIC (P<or=0.001). A concentration-dependent PAE was demonstrated
      with CSA-13, nearly doubling from 2x to 4x the MIC (P=0.03). With respect to the
      CSA-13 antimicrobial combinations, time-kill curve analysis showed no difference
      in the log10 CFU/ml at 24 h for the majority of the organisms tested. However,
      early synergy at 4 to 8 h was detected against the VRSA Pennsylvania strain
      (2002) when CSA-13 was tested in combination with gentamicin, while early
      additivity was demonstrated against all of the other organisms.

PMID- 17210766
TI  - Appropriateness of antimicrobial therapy measured by repeated prevalence surveys.
AB  - Prudent use of antibiotics is mandatory to control antibiotic resistance. The
      objective of this study was to determine if prevalence surveys are useful tools
      to determine the appropriateness of antimicrobial therapy (AMT) and determinants
      of inappropriate AMT. The study was performed in a 1,350-bed teaching hospital
      including all medical specialties. Six consecutive 1-day prevalence surveys of in
      patients were performed twice yearly from 2001 to 2004. Data on the demographics,
      infections, and AMT were gathered. The appropriateness of AMT was assessed
      according to a standardized algorithm based on the local AMT prescription
      guidelines. On average, 684 patients were included in each survey (total, 4,105).
      The use of AMT as determined in the prevalence survey corresponded to the annual
      data from the pharmacy department. Nine hundred thirty-eight (22.9%) of the
      patients received AMT, and in 351 (37.4%) of these patients AMT was
      inappropriate. Only 25 (0.6%) patients did not receive AMT, although it was
      indicated. After multivariate analysis, the use of quinolones was the only
      statistically significant variable associated with inappropriate use. Prevalence
      surveys proved to be useful tools to judge the appropriateness of AMT and to
      identify determinants of inappropriate use. This study shows that in a setting
      with a low use of AMT, there are few patients who inadvertently do not receive
      AMT. On the other hand, a substantial number of the patients are treated
      inappropriate.

PMID- 17210767
TI  - Substrate competition studies using whole-cell accumulation assays with the major
      tripartite multidrug efflux pumps of Escherichia coli.
AB  - AcrAB-TolC is the major, constitutively expressed tripartite multidrug efflux
      system in Escherichia coli that recognizes various structurally unrelated
      molecules, including many antibiotics, dyes, and steroids. The AcrB inner
      membrane pump portion of the efflux system has been shown in recent structural
      studies to bind substrates at multiple sites, suggesting that particular
      substrate "sets" may compete for efflux by interfering with a certain binding
      site(s). However, our data indicate that the general structural class does not
      appear to dictate a particular substrate binding site that can be competitively
      inhibited in whole cells. In our study, substrate competition failed to increase
      cell-associated levels of steroids or dyes to levels characteristic of AcrB- or
      AcrB/EmrAB-deficient genomic mutants or achieved with the pump inhibitor carbonyl
      cyanide m-chlorophenylhydrazone. In addition, this general observation was
      sustained even with (i) a cocktail containing seven-pump substrates supplied
      slightly below their respective wild-type MIC levels, (ii) competing drug
      substrates of the same structural class (steroids or macrolides), and (iii) hyper
      MIC levels of the exogenously supplied agents. Thus, this pump system (and
      possibly EmrAB-TolC) may have an extraordinary capacity to simultaneously handle
      multiple-drug substrates that is not necessarily reflected in MIC analyses. In
      addition, our study has extended the range of substrates recognized by the AcrAB-
      and EmrAB-TolC systems.

PMID- 17210768
TI  - Pharmacokinetic interaction between darunavir boosted with ritonavir and
      omeprazole or ranitidine in human immunodeficiency virus-negative healthy
      volunteers.
AB  - Darunavir (DRV; TMC114; Prezista) is a human immunodeficiency virus (HIV)
      protease inhibitor used in combination with low-dose ritonavir (RTV) (DRV/r) as a
      pharmacokinetic enhancer. Protease inhibitor absorption may be decreased during
      coadministration of drugs that limit stomach acid secretion and increase gastric
      pH. This study was conducted to investigate the effect of ranitidine and
      omeprazole on the plasma pharmacokinetics of DRV and RTV in HIV-negative healthy
      volunteers. Sixteen volunteers completed the study and received DRV/r, DRV/r plus
      ranitidine, and DRV/r plus omeprazole, in three separate sessions. Treatment was
      given for 4 days with an additional morning dose on day 5, and regimens were
      separated by a washout period of 7 days. Samples were taken over a 12-h period on
      day 5 for the assessment of DRV and RTV plasma concentrations. Pharmacokinetic
      parameters assessed included DRV area under the curve, maximum plasma
      concentration, and trough plasma concentration. The least-squares mean ratios and
      90% confidence intervals are reported with treatment of DRV/r alone as a
      reference. Compared with DRV/r alone, no significant changes in DRV
      pharmacokinetic parameters were observed during coadministration of DRV/r and
      either ranitidine or omeprazole. Treatment regimens were generally well
      tolerated, and no serious adverse events were reported. In conclusion,
      coadministration of DRV/r and ranitidine or omeprazole was well tolerated by the
      volunteers. Ranitidine and omeprazole did not have a significant influence on DRV
      pharmacokinetics. No dose adjustments are required when DRV/r is coadministered
      with omeprazole or ranitidine.

PMID- 17210770
TI  - Activity of linezolid against 3,251 strains of uncommonly isolated gram-positive
      organisms: report from the SENTRY Antimicrobial Surveillance Program.
AB  - Linezolid was tested against 32 species of uncommonly isolated gram-positive
      organisms (3,251 strains) by reference MIC methods and found to be highly active
      (MIC50 range, 0.25 to 2 microg/ml; MIC90 range, 0.25 to 2 microg/ml). Only one
      isolate (viridans group streptococcus; 0.03% of tested strains) was resistant to
      linezolid.

PMID- 17210769
TI  - Azithromycin selectively reduces tumor necrosis factor alpha levels in cystic
      fibrosis airway epithelial cells.
AB  - Azithromycin (AZM) ameliorates lung function in cystic fibrosis (CF) patients.
      This macrolide has been suggested to have anti-inflammatory properties as well as
      other effects potentially relevant for therapy of CF. In this study, we utilized
      three CF (IB3-1, 16HBE14o- AS3, and 2CFSMEo-) and two isogenic non-CF (C38 and
      16HBE14o- S1) airway epithelial cell lines to investigate whether AZM could
      reduce tumor necrosis factor alpha (TNF-alpha) mRNA and protein levels by real
      time quantitative PCR analysis and an enzyme-linked immunosorbent assay (ELISA),
      respectively. We studied the effects on the DNA binding of NF-kappaB and
      specificity protein 1 (Sp1) by an ELISA. Non-CF cells express significantly lower
      TNF-alpha mRNA and protein levels than an isogenic CF cell line. In CF cells, AZM
      treatment causes a 30% reduction of TNF-alpha mRNA levels (P < 0.05) and a 45%
      decrease in TNF-alpha secretion (P < 0.05), reaching approximately the levels of
      the untreated isogenic non-CF cells. In CF cells, NF-kappaB and Sp1 DNA binding
      activities were also significantly decreased (about 45 and 60%, respectively; P <
      0.05) after AZM treatment. Josamycin, a macrolide lacking clinically described
      anti-inflammatory effects, was ineffective. Finally, AZM did not alter the mRNA
      expression levels of interleukin-6, a proinflammatory molecule not differentially
      expressed in CF and isogenic non-CF cells. The results of our study support the
      anti-inflammatory activities of this macrolide, since we show that AZM reduced
      the levels of TNF-alpha and propose inhibitions of NF-kappaB and Sp1 DNA binding
      as possible mechanisms of this effect.

PMID- 17210771
TI  - Posaconazole plasma concentrations in juvenile patients with invasive fungal
      infection.
AB  - Posaconazole is an orally bioavailable triazole antifungal agent for the
      treatment and prophylaxis of invasive fungal infection. We evaluated plasma
      posaconazole concentration data from juvenile (younger than 18 years; n = 12) and
      adult (18 to 64 years; n = 194) patients who participated in a multicenter, phase
      3, open-label study that assessed the efficacy and safety of posaconazole
      treatment for persons who were intolerant of or had invasive fungal infection
      refractory to standard antifungal therapies. With the exception of one juvenile
      patient who received 400 mg/day as a divided dose on the day of sample
      collection, all patients received posaconazole at 800 mg/day as an oral
      suspension in divided doses. Plasma samples were analyzed through a validated
      liquid chromatographic-tandem mass spectrometric method with a lower limit of
      quantitation of 1 ng/ml. Because plasma posaconazole concentrations are
      relatively constant at steady state, the average of all plasma concentrations
      (C(av)) for each patient was calculated to provide a single steady-state plasma
      posaconazole concentration. A blinded data review committee reviewed all
      treatment outcomes. Variable posaconazole plasma concentrations were observed
      within both the juvenile and adult populations. Mean (median [range]) C(av)
      values for juvenile and adult patients were 776 ng/ml (579 ng/ml [85.3 to 2,891
      ng/ml]) and 817 ng/ml (626 ng/ml [0 to 3,710 ng/ml]), respectively. Overall
      success rates and adverse event profiles were comparable. In conclusion,
      posaconazole concentrations in plasma were similar for juvenile and adult
      patients, suggesting that clinical outcomes are expected to be similar in adults
      and children with refractory invasive fungal infection.

PMID- 17210772
TI  - Clonal diversity and resistance mechanisms in tetracycline-nonsusceptible
      Streptococcus pneumoniae isolates in Poland.
AB  - The frequency of tetracycline resistance in Streptococcus pneumoniae isolates in
      Poland is one of the highest in Europe. The aim of this study was to analyze the
      clonal diversity and resistance determinants of tetracycline-nonsusceptible S.
      pneumoniae isolates identified in Poland and to investigate the effect of
      tetracycline resistance on their susceptibilities to tigecycline, doxycycline,
      and minocycline. We have analyzed 866 pneumococcal isolates collected from 1998
      to 2003 from patients with respiratory tract diseases, and 242 of these (27.9%)
      were found to be resistant to tetracycline. All of the resistant isolates were
      characterized by testing of their susceptibilities to other antimicrobials,
      serotyping, pulsed-field gel electrophoresis (PFGE), and identification of
      tetracycline resistance genes and transposons. Selected isolates representing the
      main PFGE types were analyzed by multilocus sequence typing. Among the isolates
      investigated, 27 serotypes and 146 various PFGE patterns, grouped into 90 types,
      were discerned. The most common PFGE type, corresponding to serotype 19F and
      sequence type 423, was represented by 22.3% of all of the tetracycline-resistant
      isolates. The tet(M) gene was the sole resistance gene in the group of isolates
      studied, and in over 96% of the isolates, the Tn916 family of tet(M)-containing
      conjugative transposons was detected. Several isolates contained specific
      variants of the transposons, the Tn1545-like, Tn3872-like, or Tn2009-like
      element. The correlation between the MICs of tetracycline, doxycycline, and
      minocycline was revealed, whereas no cross-resistance to tetracycline and
      tigecycline was observed.

PMID- 17210773
TI  - In vitro activity of the oxazolidinone RWJ-416457 against linezolid-resistant and
      -susceptible staphylococci and enterococci.
AB  - RWJ-416457, a novel oxazolidinone, had modal MICs of 0.5 to 1 microg/ml for
      linezolid-susceptible staphylococci and enterococci, versus linezolid MICs for
      these organisms of 1 or 2 microg/ml. RWJ-416457 MICs for mutants with 23S rRNA
      mutations were 2 to 32 microg/ml, versus linezolid MICs of 8 to 64 microg/ml;
      actual values reflected the proportion of gene copies mutated.

PMID- 17210774
TI  - Rapid genotyping of CTX-M extended-spectrum beta-lactamases by denaturing high
      performance liquid chromatography.
AB  - Denaturing high-performance liquid chromatography (dHPLC) is a powerful technique
      which has been used extensively to detect genetic variation. This is the first
      report of the application of dHPLC for rapid genotyping of bacterial beta
      lactamase genes. The technique was specifically developed to genotype members of
      all blaCTX-M DNA homology groups. Thirteen well-defined blaCTX-M extended
      spectrum beta-lactamase (ESBL)-producing strains were used to develop and
      optimize the dHPLC genotyping assay. Further evaluation was carried out with a
      blinded panel of 62 clinical isolates. The results of blaCTX-M genotyping
      achieved by dHPLC were comparable to the typing results obtained by DNA
      sequencing. Applying the newly developed dHPLC-based genotyping method, we
      successfully genotyped all 73 blaCTX-M ESBL-producing strains from the 4-month
      survey study. Furthermore, we found the first reported cases in the United
      Kingdom of clinically significant disease caused by CTX-M-14- and CTX-M-1
      producing Escherichia coli strains. We conclude that the novel dHPLC assay is
      highly accurate, rapid, and cost-effective for the genotyping of blaCTX-M
      producing ESBLs and has great potential for determining the clinical relevance of
      different and new blaCTX-M genotypes, as well as for epidemiological studies and
      surveillance programs.

PMID- 17210775
TI  - Low-oxygen-recovery assay for high-throughput screening of compounds against
      nonreplicating Mycobacterium tuberculosis.
AB  - Screening for new antimicrobial agents is routinely conducted only against
      actively replicating bacteria. However, it is now widely accepted that a
      physiological state of nonreplicating persistence (NRP) is responsible for
      antimicrobial tolerance in many bacterial infections. In tuberculosis, the key to
      shortening the 6-month regimen lies in targeting this NRP subpopulation.
      Therefore, a high-throughput, luminescence-based low-oxygen-recovery assay (LORA)
      was developed to screen antimicrobial agents against NRP Mycobacterium
      tuberculosis. M. tuberculosis H37Rv containing a plasmid with an acetamidase
      promoter driving a bacterial luciferase gene was adapted to low oxygen conditions
      by extended culture in a fermentor with a 0.5 headspace ratio. The MICs of 31
      established antimicrobial agents were determined in microplate cultures
      maintained under anaerobic conditions for 10 days and, for comparative purposes,
      under aerobic conditions for 7 days. Cultures exposed to drugs under anaerobic
      conditions followed by 28 h of "recovery" under ambient oxygen produced a
      luminescent signal that was, for most compounds, proportional to the number of
      CFU determined prior to the recovery phase. No agents targeting the cell wall
      were active against NRP M. tuberculosis, whereas drugs hitting other cellular
      targets had a range of activities. The calculated Z' factor was in the range of
      0.58 to 0.84, indicating the suitability of the use of LORA for high-throughput
      assays. This LORA is sufficiently robust for use for primary high-throughput
      screening of compounds against NRP M. tuberculosis.

PMID- 17210776
TI  - Antibiotic resistance of Campylobacter jejuni and Campylobacter coli clinical
      isolates from Poland.
AB  - We tested 102 Campylobacter jejuni and 6 Campylobacter coli clinical isolates
      from Poland. All were susceptible to erythromycin. Among the tested C. jejuni
      isolates 55.9% and 13.7% were resistant to ciprofloxacin and tetracycline,
      respectively. Replacement of Thr86 with Ile in GyrA and a plasmid-borne tet(O)
      gene were the main resistance mechanisms for fluoroquinolones and tetracycline,
      respectively.

PMID- 17210777
TI  - Independent evolution of pyrimethamine resistance in Plasmodium falciparum
      isolates in Melanesia.
AB  - Pyrimethamine resistance in Plasmodium falciparum has previously been shown to
      have emerged once in Southeast Asia, from where it spread to Africa.
      Pyrimethamine resistance in this parasite is known to be conferred by mutations
      in the gene encoding dihydrofolate reductase (dhfr). We have analyzed
      polymorphisms in dhfr as well as microsatellite haplotypes flanking this gene in
      a total of 285 isolates from different regions of Melanesia (Papua New Guinea,
      Vanuatu, and the Solomon Islands) and Southeast Asia (Thailand and Cambodia).
      Nearly all isolates (92%) in Melanesia were shown to carry a dhfr double mutation
      (CNRNI [underlining indicates the mutation]) at positions 50, 51, 59, 108, and
      164, whereas 98% of Southeast Asian isolates were either triple (CIRNI) or
      quadruple (CIRNL) mutants. Microsatellite analysis revealed two distinct lineages
      of dhfr double mutants in Melanesia. One lineage had the same microsatellite
      haplotype as that previously reported for Southeast Asia and Africa, suggesting
      the spread of this allele to Melanesia from Southeast Asia. The other lineage had
      a unique, previously undescribed microsatellite haplotype, indicative of the de
      novo emergence of pyrimethamine resistance in Melanesia.

PMID- 17210778
TI  - Effects of glutathione and ascorbic acid on streptomycin sensitivity of
      Escherichia coli.
AB  - We examined the effects of antioxidants and the role of reactive oxygen species
      (ROS) on the antibacterial action of aminoglycosides in Escherichia coli. We
      concluded that reduced streptomycin sensitivity in the presence of glutathione
      and ascorbic acid is not due to the antioxidant-mediated scavenging of ROS.

PMID- 17210779
TI  - Diminished ciprofloxacin-induced chondrotoxicity by supplementation with
      magnesium and vitamin E in immature rats.
AB  - Quinolone-induced chondrotoxicity in juvenile rats and multiple other species has
      been demonstrated previously. Identical damages can be induced in immature rats
      by feeding them a magnesium-deficient diet. The objective of the present study
      was to investigate whether, in reverse, oral supplementation with magnesium,
      vitamin E, or both can diminish the typical quinolone-induced arthropathy in
      juvenile Wistar rats. Four groups of 12 (6 male, 6 female) 24-day-old Wistar rats
      were each fed either normal feed (group A), a vitamin E-enriched diet (group B),
      a magnesium-enriched diet (group C), or a diet enriched with both vitamin E and
      magnesium (group D) for 10 days. All rats received two subcutaneous ciprofloxacin
      doses of 600 mg/kg of body weight on postnatal day 32. Two days later, the rats
      were sacrificed and cartilage samples from knee joints were examined under a
      light microscope for the presence of typical quinolone-induced joint cartilage
      lesions. In addition, magnesium, calcium, and vitamin E concentrations in
      cartilage and plasma were determined. In the samples from rats fed a normal diet
      (group A), 17 quinolone-induced joint cartilage lesions were observed. In groups
      fed an enriched diet, the incidence of specific lesions (n) was significantly
      lower: group B, n = 10 (41% reduction compared to the incidence for group A; P <
      0.05); group C, n = 6 (65% reduction; P < 0.01); and group D, n = 3 (82%
      reduction; P < 0.01). In comparison to the standard diet, diets with magnesium
      and vitamin E supplementation resulted in significantly higher magnesium and
      vitamin E concentrations in plasma and articular cartilage. Supplementation with
      magnesium and vitamin E alone or in combination may relevantly diminish joint
      cartilage lesions induced by quinolones in immature rats, with an additive effect
      of combined supplementation. The data further support the proposed pathomechanism
      of quinolone-induced arthropathy and the crucial role of magnesium in immature
      joint cartilage.

PMID- 17210780
TI  - Molecular basis for susceptibility of plasma platelet-activating factor
      acetylhydrolase to oxidative inactivation.
AB  - Platelet-activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 that
      inactivates potent lipid messengers, such as PAF and modified phospholipids
      generated in settings of oxidant stress. The catalytic activity of PAF-AH is
      sensitive to oxidants, a feature that may have pathological consequences. We
      report that peroxynitrite, an oxidant species generated after cellular
      activation, mediates oxidative inactivation of PAF-AH. We found that
      peroxynitrite inactivated and derivatized the recombinant protein and obtained
      evidence supporting a role for a methionine and two tyrosine residues in this
      process. We employed interspecies comparisons and site-directed mutagenesis and
      identified a role for M-117, and a smaller contribution of Y-307 and Y-335 as
      targets of oxidant attack using free and lipoprotein-associated recombinant
      proteins. M-117 is adjacent to W-115 and L-116, which are essential for
      association of PAF-AH with LDL. Oxidation of LDL-associated PAF-AH partially
      dissociated the enzyme from the particles. Similarly, oxidation of the purified
      enzyme in the absence of lipoproteins prevented subsequent association with LDL.
      These results provide new insights into the molecular mechanisms that mediate
      inactivation of PAF-AH in settings of oxidant stress and the consequences of
      oxidation on the ability of this enzyme to associate with LDL.

PMID- 17210781
TI  - Cooperative and redundant roles of VEGFR-2 and VEGFR-3 signaling in adult
      lymphangiogenesis.
AB  - Activation of vascular endothelial growth factor (VEGF) receptor-3 (VEGFR-3) by
      VEGF-C initiates lymphangiogenesis by promoting lymphatic proliferation and
      migration. However, it is unclear whether VEGFR-3 signaling is required beyond
      these initial stages, namely during the organization of new lymphatic endothelial
      cells (LECs) into functional capillaries. Furthermore, the role of VEGFR-2, which
      is also expressed on LECs and binds VEGF-C, is unclear. We addressed these
      questions by selectively neutralizing VEGFR-3 and/or VEGFR-2 for various time
      periods in an adult model of lymphangiogenesis in regenerating skin. While
      blocking either VEGFR-2 or VEGFR-3 with specific antagonist mAbs (DC101 and mF4
      31C1, respectively) prior to lymphatic migration prevented lymphangiogenesis,
      blocking VEGFR-3 subsequent to migration did not affect organization into
      functional capillaries, and VEGFR-2 blocking had only a small hindrance on
      organization. These findings were confirmed in vitro using human LECs and anti
      human antagonist mAbs (IMC-1121a and hF4-3C5): both VEGFR-2 and -3 signaling were
      required for migration and proliferation, but tubulogenesis in 3D cultures was
      unaffected by VEGFR-3 blocking and partially hindered by VEGFR-2 blocking.
      Furthermore, both in vitro and in vivo, while VEGFR-3 blocking had no effect on
      LEC organization, coneutralization of VEGFR-2, and VEGFR-3 completely prevented
      lymphatic organization. Our findings demonstrate that cooperative signaling of
      VEGFR-2 and -3 is necessary for lymphatic migration and proliferation, but VEGFR
      3 is redundant with VEGFR-2 for LEC organization into functional capillaries.

PMID- 17210782
TI  - Overexpression of tetraspanins affects multiple myeloma cell survival and
      invasive potential.
AB  - Cellular interactions with microenvironmental components are critical in multiple
      myeloma (MM) and impede effective disease treatment. Membranal-embedded
      tetraspanins, associated with metastasis suppression, are underexpressed in MM.
      We aimed to investigate the consequences of CD81/CD82 tetraspanins over
      expression in MM cell lines. CAG and RPMI 8226 were transfected with pEGFP-N1/C1
      fusion vectors of CD81/CD82. Employing flow cytometry, immunocytochemistry, and
      activity assays we assessed transfected cells for: morphology, survival, death,
      caspases, cell cycle, proliferation, oxidative stress, adhesion, motility and
      invasion. Overexpressed CD81/CD82 pEGFP-N1 vectors reduced survival without
      elevation of pre-G1 or AnnexinV+/7AAD- and independently of caspases. Decreased
      Ki67 and elevated intracellular glutathione were detected. No perturbations in
      cell cycle distribution were observed. The pEGFP-C1 vectors of CD81/CD82 caused
      reduction of MM cell adherence with/without fibronectin, insulin-like growth
      factor (IGF)-I, and matrigel. They also reduced cell motility and attenuated
      invasion potential, expressed by reduced secreted MMP-9 activity. These novel
      findings delineate the significance of CD81/CD82 expression to MM cell survival
      and their negative effects on cell adhesion, motility, and invasion thus,
      supporting their role as tumor metastasis suppressors.

PMID- 17210783
TI  - Oncogenes and senescence: breaking down in the fast lane.

PMID- 17210784
TI  - Determinants of regulated proteolysis in signal transduction.

PMID- 17210785
TI  - Eukaryotic regulatory RNAs: an answer to the 'genome complexity' conundrum.
AB  - A large portion of the eukaryotic genome is transcribed as noncoding RNAs
      (ncRNAs). While once thought of primarily as "junk," recent studies indicate that
      a large number of these RNAs play central roles in regulating gene expression at
      multiple levels. The increasing diversity of ncRNAs identified in the eukaryotic
      genome suggests a critical nexus between the regulatory potential of ncRNAs and
      the complexity of genome organization. We provide an overview of recent advances
      in the identification and function of eukaryotic ncRNAs and the roles played by
      these RNAs in chromatin organization, gene expression, and disease etiology.

PMID- 17210786
TI  - The DNA damage signaling pathway is a critical mediator of oncogene-induced
      senescence.
AB  - Here we report that RNA interference against ATM inhibited p53 accumulation in
      cells expressing oncogenic STAT5 and cooperated with Rb inactivation to suppress
      STAT5A-induced senescence. Knocking down ATM was also effective to bypass E2F1
      induced senescence and in combination with Rb inactivation, inhibited RasV12
      induced senescence. Cells that senesced in response to ca-STAT5A or RasV12
      accumulated DNA damage foci and activated ATM, ATR, Chk1, and Chk2, indicating
      that aberrant oncogene activation induces a DNA damage signaling response.
      Intriguingly, bypassing oncogene-induced senescence by inactivation of p53 and Rb
      did not eliminate the accumulation of oncogene-induced DNA damage foci (ODDI),
      suggesting a mechanism that may limit transformation in immortalized cells.

PMID- 17210787
TI  - pRB family proteins are required for H3K27 trimethylation and Polycomb repression
      complexes binding to and silencing p16INK4alpha tumor suppressor gene.
AB  - Genetic studies have demonstrated that Bmi1 promotes cell proliferation and stem
      cell self-renewal with a correlative decrease of p16(INK4a) expression. Here, we
      demonstrate that Polycomb genes EZH2 and BMI1 repress p16 expression in human and
      mouse primary cells, but not in cells deficient for pRB protein function. The p16
      locus is H3K27-methylated and bound by BMI1, RING2, and SUZ12. Inactivation of
      pRB family proteins abolishes H3K27 methylation and disrupts BMI1, RING2, and
      SUZ12 binding to the p16 locus. These results suggest a model in which pRB
      proteins recruit PRC2 to trimethylate p16, priming the BMI1-containing PRC1L
      ubiquitin ligase complex to silence p16.

PMID- 17210788
TI  - A mutation in separase causes genome instability and increased susceptibility to
      epithelial cancer.
AB  - Proper chromosome segregation is essential for maintenance of genomic integrity
      and instability resulting from failure of this process may contribute to cancer.
      Here, we demonstrate that a mutation in the mitotic regulator separase is
      responsible for the cell cycle defects seen in the zebrafish mutant, cease&desist
      (cds). Analysis of cds homozygous mutant embryos reveals high levels of
      polyploidy and aneuploidy, spindle defects, and a mitotic exit delay.
      Carcinogenesis studies demonstrated that cds heterozygous adults have a shift in
      tumor spectrum with an eightfold increase in the percentage of fish bearing
      epithelial tumors, indicating that separase is a tumor suppressor gene in
      vertebrates. These data strongly support a conserved cross-species role for
      mitotic checkpoint genes in genetic stability and epithelial carcinogenesis.

PMID- 17210789
TI  - labA: a novel gene required for negative feedback regulation of the
      cyanobacterial circadian clock protein KaiC.
AB  - In the cyanobacterium Synechococcus elongatus PCC 7942, circadian timing is
      transmitted from the KaiABC-based central oscillator to the transcription factor
      RpaA via the KaiC-interacting histidine kinase SasA to activate transcription,
      thereby generating rhythmic circadian gene expression. However, KaiC can also
      repress circadian gene expression, including its own. The mechanism and
      significance of this negative feedback regulation have been unclear. Here, we
      report a novel gene, labA (low-amplitude and bright), that is required for
      negative feedback regulation of KaiC. Disruption of labA abolished
      transcriptional repression caused by overexpression of KaiC and elevated the
      trough levels of circadian gene expression, resulting in a low-amplitude
      phenotype. In contrast, overexpression of labA significantly lowered circadian
      gene expression. Furthermore, genetic analysis indicated that labA and sasA
      function in parallel pathways to regulate kaiBC expression, whereas rpaA
      functions downstream from labA for kaiBC expression. These results suggest that
      temporal information from the KaiABC-based oscillator diverges into a LabA
      dependent negative pathway and a SasA-dependent positive pathway, and then
      converges onto RpaA to generate robust circadian gene expression. It is likely
      that quantitative information of KaiC is transmitted to RpaA through LabA,
      whereas SasA mediates the state of the KaiABC-based oscillator.

PMID- 17210790
TI  - MicroRNAs regulate the expression of the alternative splicing factor nPTB during
      muscle development.
AB  - Alternative pre-mRNA splicing determines many changes in gene expression during
      development. Two regulators known to control splicing patterns during neuron and
      muscle differentiation are the polypyrimidine tract-binding protein (PTB) and its
      neuronal homolog nPTB. These proteins repress certain exons in early myoblasts,
      but upon differentiation of mature myotubes PTB/nPTB expression is reduced,
      leading to increased inclusion of their target exons. We show here that the
      repression of nPTB expression during myoblast differentiation results from its
      targeting by the muscle-restricted microRNA miR-133. During differentiation of
      C2C12 myoblasts, nPTB protein but not mRNA expression is strongly reduced,
      concurrent with the up-regulation of miR-133 and the induction of splicing for
      several PTB-repressed exons. Introduction of synthetic miR-133 into
      undifferentiated C2C12 cells leads to a decrease in endogenous nPTB expression.
      Both the miR-133 and the coexpressed miR-1/206 microRNAs are extremely conserved
      across animal species, and PTB proteins are predicted targets for these miRNAs in
      Drosophila, mice, and humans. There are two potential miR-133-responsive elements
      (MRE) within the nPTB 3' untranslated region (UTR), and a luciferase reporter
      carrying this 3' UTR is repressed by miR-133 in an MRE-dependent manner.
      Transfection of locked nucleic acid (LNA) oligonucleotides designed to block the
      function of miR-133 and miR-1/206 increases expression of nPTB and decreases the
      inclusion of PTB dependent exons. These results indicate that miR-133 directly
      down-regulates a key splicing factor during muscle development and establishes a
      role for microRNAs in the control of a developmentally dynamic splicing program.

PMID- 17210791
TI  - Rb is critical in a mammalian tissue stem cell population.
AB  - The inactivation of the retinoblastoma (Rb) tumor suppressor gene in mice results
      in ectopic proliferation, apoptosis, and impaired differentiation in
      extraembryonic, neural, and erythroid lineages, culminating in fetal death by
      embryonic day 15.5 (E15.5). Here we show that the specific loss of Rb in
      trophoblast stem (TS) cells, but not in trophoblast derivatives, leads to an
      overexpansion of trophoblasts, a disruption of placental architecture, and fetal
      death by E15.5. Despite profound placental abnormalities, fetal tissues appeared
      remarkably normal, suggesting that the full manifestation of fetal phenotypes
      requires the loss of Rb in both extraembryonic and fetal tissues. Loss of Rb
      resulted in an increase of E2f3 expression, and the combined ablation of Rb and
      E2f3 significantly suppressed Rb mutant phenotypes. This rescue appears to be
      cell autonomous since the inactivation of Rb and E2f3 in TS cells restored
      placental development and extended the life of embryos to E17.5. Taken together,
      these results demonstrate that loss of Rb in TS cells is the defining event
      causing lethality of Rb(-/-) embryos and reveal the convergence of extraembryonic
      and fetal functions of Rb in neural and erythroid development. We conclude that
      the Rb pathway plays a critical role in the maintenance of a mammalian stem cell
      population.

PMID- 17210792
TI  - Bcl2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma.
AB  - Glioblastoma (GBM) is an astrocytic brain tumor characterized by an aggressive
      clinical course and intense resistance to all therapeutic modalities. Here, we
      report the identification and functional characterization of Bcl2L12 (Bcl2-like
      12) that is robustly expressed in nearly all human primary GBMs examined.
      Enforced Bcl2L12 expression confers marked apoptosis resistance in primary
      cortical astrocytes, and, conversely, its RNA interference (RNAi)-mediated
      knockdown sensitizes human glioma cell lines toward apoptosis in vitro and
      impairs tumor growth with increased intratumoral apoptosis in vivo.
      Mechanistically, Bcl2L12 expression does not affect cytochrome c release or
      apoptosome-driven caspase-9 activation, but instead inhibits post-mitochondrial
      apoptosis signaling at the level of effector caspase activation. One of Bcl2L12's
      mechanisms of action stems from its ability to interact with and neutralize
      caspase-7. Notably, while enforced Bcl2L12 expression inhibits apoptosis, it also
      engenders a pronecrotic state, which mirrors the cellular phenotype elicited by
      genetic or pharmacologic inhibition of post-mitochondrial apoptosis molecules.
      Thus, Bcl2L12 contributes to the classical tumor biological features of GBM such
      as intense apoptosis resistance and florid necrosis, and may provide a target for
      enhanced therapeutic responsiveness of this lethal cancer.

PMID- 17210793
TI  - Design principles of the proteolytic cascade governing the sigmaE-mediated
      envelope stress response in Escherichia coli: keys to graded, buffered, and rapid
      signal transduction.
AB  - Proteolytic cascades often transduce signals between cellular compartments, but
      the features of these cascades that permit efficient conversion of a biological
      signal into a transcriptional output are not well elucidated. sigma(E) mediates
      an envelope stress response in Escherichia coli, and its activity is controlled
      by regulated degradation of RseA, a membrane-spanning anti-sigma factor.
      Examination of the individual steps in this protease cascade reveals that the
      initial, signal-sensing cleavage step is rate-limiting; that multiple ATP
      dependent proteases degrade the cytoplasmic fragment of RseA and that
      dissociation of sigma(E) from RseA is so slow that most free sigma(E) must be
      generated by the active degradation of RseA. As a consequence, the degradation
      rate of RseA is set by the amount of inducing signal, and insulated from the
      "load" on and activity of the cytoplasmic proteases. Additionally, changes in
      RseA degradation rate are rapidly reflected in altered sigma(E) activity. These
      design features are attractive as general components of signal transduction
      pathways governed by unstable negative regulators.

PMID- 17210794
TI  - Effect of elevated serum uric acid on cisplatin-induced acute renal failure.
AB  - Marked hyperuricemia is known to cause acute renal failure via intrarenal crystal
      deposition. However, recent studies suggest mild hyperuricemia may have
      vasoactive and proinflammatory effects independent of crystal formation. We
      therefore tested the hypothesis that mild hyperuricemia might exacerbate renal
      injury and dysfunction in a model of cisplatin-induced acute renal failure in the
      rat. Cisplatin was administered to normouricemic and hyperuricemic rats (the
      latter generated by administering the urate oxidase inhibitor, oxonic acid).
      Recombinant urate oxidase (rasburicase) was administered in a third group to
      assess the effect of lowering uric acid on outcomes. Other control groups include
      normal rats and hyperuricemic rats without cisplatin-induced injury. Cisplatin
      induced injury of the pars recta (S3) segment of the proximal tubule in
      association with a mild monocyte infiltration. Hyperuricemic rats showed
      significantly greater tubular injury and proliferation with significantly greater
      macrophage infiltration and increased expression of monocyte chemoattractant
      protein-1. However, renal function was not different between normouricemic and
      hyperuricemic rats with cisplatin injury. Treatment with rasburicase reversed the
      inflammatory changes and lessened tubular injury with an improvement in renal
      function (relative to the hyperuricemic group). No intrarenal crystals were
      observed in any groups. These data provide the first experimental evidence that
      uric acid, at concentrations that do not cause intrarenal crystal formation, may
      exacerbate renal injury in a model of acute renal failure. The mechanism may
      relate to a proinflammatory pathway involving chemokine expression with leukocyte
      infiltration.

PMID- 17210795
TI  - Evidence for HSP-mediated cytoskeletal stabilization in mesothelial cells during
      acute experimental peritoneal dialysis.
AB  - Low biocompatibility of peritoneal dialysis fluid (PDF) injures mesothelial cells
      and activates their stress response. In this study, we investigated the role of
      heat shock proteins (HSP), the main cytoprotective effectors of the stress
      response, in cytoskeletal stabilization of mesothelial cells in experimental
      peritoneal dialysis. In cultured human mesothelial cells, cytoskeletal integrity
      was assessed by detergent extractability of marker proteins following in vitro
      PDF exposure. Effects of HSP on stabilization of ezrin were evaluated by a
      conditioning protocol (PDF pretreatment) and repair assay, based on coincubation
      of cytoskeletal protein fractions with recombinant HSP-72 or HSP-72 antibodies.
      In the rat model, detachment of mesothelial cells from their peritoneal monolayer
      during in vivo PDF exposure was assessed with and without overexpression of HSP
      72 (by heat conditioning). In vitro, cytoskeletal disruption on sublethal PDF
      exposure was demonstrated by significantly altered detergent extractability of
      ezrin and ZO-1. Restoration was associated with significant induction and
      cytoskeletal redistribution of HSP during recovery. Both the conditioning
      protocol and in vitro repair assay provided evidence for HSP-72-mediated
      cytoskeletal stabilization. In the rat model, overexpression of HSP-72 following
      heat conditioning resulted in significantly reduced detachment of mesothelial
      cells on in vivo exposure to PDF. Our results establish an essential role of HSP
      in repair and cytoprotection of cytoskeletal integrity in mesothelial cells
      following acute in vitro and in vivo exposure to PDF. Repeated exposure to PDF,
      as is the rule in the clinical setting, may not only cause repeat injury to
      mesothelial cells but rather represents a kind of inadvertent conditioning
      treatment.

PMID- 17210796
TI  - Evidence that postprandial reduction of renal calcium reabsorption mediates
      hypercalciuria of patients with calcium nephrolithiasis.
AB  - Idiopathic hypercalciuria (IH) is common among calcium stone formers (IHSF). The
      increased urinary calcium arises from increased intestinal absorption of calcium,
      but it is unclear whether increased filtered load or decreased renal tubular
      reabsorption of calcium is the main mechanism for the increased renal excretion.
      To explore this question, 10 IHSF and 7 normal subjects (N) were studied for 1
      day. Urine and blood samples were collected at 30- to 60-min intervals while
      subjects were fasting and after they ate three meals providing known amounts of
      calcium, phosphorus, sodium, protein, and calories. Fasting and fed,
      ultrafiltrable calcium levels, and filtered load of calcium did not differ
      between N and IHSF. Urine calcium rose with meals, and fractional reabsorption
      fell in all subjects, but the change was significantly higher in IHSF. The
      changes in calcium excretion were independent of sodium excretion. Serum
      parathyroid hormone levels did not differ between N and IHSF, and they could not
      account for the greater fall in calcium reabsorption in IHSF. Serum magnesium and
      phosphorus levels in IHSF were below N throughout the day, and tubule phosphate
      reabsorption was lower in IHSF than N after meals. The primary mechanism by which
      kidneys ferry absorbed calcium into the urine after meals is via reduced tubule
      calcium reabsorption, and IHSF differ from N in the magnitude of the response.
      Parathyroid hormone is not likely to be a sufficient explanation for this
      difference.

PMID- 17210797
TI  - Mitochondrial c-Jun NH2-terminal kinase prevents the accumulation of reactive
      oxygen species and reduces necrotic damage in neural tumor cells that lack
      trophic support.
AB  - In response to different stress signals, the c-Jun NH(2)-terminal kinase (JNK)
      can trigger cell death. However, JNK also facilitates the survival and cell cycle
      progression of tumor cells by mechanisms that are poorly defined. Here, we show
      that schwannoma RN22 cells can survive and proliferate under serum-free
      conditions although serum withdrawal rapidly induces mitochondrial fission and
      swelling. Although the morphologic changes observed in the mitochondria did not
      trigger cytochrome c release, they were accompanied by an increase in the
      mitochondrial membrane potential (DeltaPsi(M)) and of immunoreactivity for active
      JNK in these organelles. Pharmacologic inhibition of JNK provoked a further
      increase of the DeltaPsi(M), an increase in reactive oxygen species (ROS)
      production, and a sustained decrease in cell viability due to necrosis. This
      increase in necrosis was prevented by the presence of ROS scavengers.
      Immunoreactivity for active JNK was also observed in the mitochondria of
      neuroblastoma 1E-115 and neuroblastoma 2a neuroblastoma cell lines on serum
      withdrawal, whereas active JNK was barely detected in serum-deprived fibroblasts.
      Accordingly, the reduction in neural tumor cell viability induced by JNK
      inhibition was largely attenuated in serum-deprived fibroblasts. These data
      indicate that local activation of JNK in the mitochondria can protect against
      necrotic cell death associated with ROS production, facilitating the growth of
      neural tumor cells subjected to serum deprivation.

PMID- 17210799
TI  - Activation of vascular endothelial growth factor through reactive oxygen species
      mediates 20-hydroxyeicosatetraenoic acid-induced endothelial cell proliferation.
AB  - 20-Hydroxyeicosatetraenoic acid (20-HETE) is formed by the omega-hydroxylation of
      arachidonic acid by cytochrome P450 4A and 4F enzymes, and it induces angiogenic
      responses in vivo. To test the hypothesis that 20-HETE increases endothelial cell
      (EC) proliferation via vascular endothelial growth factor (VEGF), we studied the
      effects of WIT003 [20-hydroxyeicosa-5(Z),14(Z)-dienoic acid], a 20-HETE analog on
      human macrovascular or microvascular EC. WIT003, as well as pure 20-HETE,
      stimulated EC proliferation by approximately 40%. These proliferative effects
      were accompanied by increased VEGF expression and release that were observed as
      early as 4 h after 20-HETE agonist addition. This was accompanied by increased
      phosphorylation of the VEGF receptor 2. The proliferative effects of 20-HETE were
      markedly inhibited by a VEGF-neutralizing antibody. Polyethylene glycol
      superoxide dismutase (PEG-SOD) markedly inhibited both the increases in VEGF
      expression and the proliferative effects of 20-HETE. In contrast, administration
      of the NAD(P)H oxidase inhibitor apocynin had no effect to the proliferative
      response to 20-HETE. The 20-HETE agonist markedly increased superoxide formation
      as reflected by an increase in dihydroethidium staining of EC, and this increase
      was inhibited by PEG-SOD but not by apocynin. 20-HETE also increased the
      phosphorylation of p42/p44 mitogen-activated protein kinase (MAPK) in EC, whereas
      an inhibitor of MAPK [U0126, 1,4-diamino-2,3-dicyano-1,4-bis(2
      aminophenylthio)butadiene] suppressed the proliferative and the VEGF changes but
      not the pro-oxidant effects of 20-HETE. These data suggest that 20-HETE
      stimulates superoxide formation by pathways other than apocynin-sensitive NAD(P)H
      oxidase, thereby activating MAPK and then enhancing VEGF synthesis that drives EC
      proliferation. Thus, 20-HETE may be involved in the regulation of EC functions,
      such as angiogenesis.

PMID- 17210798
TI  - Antidepressants increase glial cell line-derived neurotrophic factor production
      through monoamine-independent activation of protein tyrosine kinase and
      extracellular signal-regulated kinase in glial cells.
AB  - Recent studies show that neuronal and glial plasticity are important for
      therapeutic action of antidepressants. We previously reported that
      antidepressants increase glial cell line-derived neurotrophic factor (GDNF)
      production in rat C6 glioma cells (C6 cells). Here, we found that amitriptyline,
      a tricyclic antidepressant, increased both GDNF mRNA expression and release,
      which were selectively and completely inhibited by mitogen-activated protein
      kinase kinase inhibitors. Indeed, treatment of amitriptyline rapidly increased
      extracellular signal-regulated kinase (ERK) activity, as well as p38 mitogen
      activated protein kinase and c-Jun NH2-terminal kinase activities. Furthermore,
      different classes of antidepressants also rapidly increased ERK activity. The
      extent of acute ERK activation and GDNF release were significantly correlated to
      each other in individual antidepressants, suggesting an important role of acute
      ERK activation in GDNF production. Furthermore, antidepressants increased the
      acute ERK activation and GDNF mRNA expression in normal human astrocytes as well
      as C6 cells. Although 5-hydroxytryptamine (serotonin) (5-HT), but not
      noradrenaline or dopamine, increased ERK activation and GDNF release via 5-HT2A
      receptors, ketanserin, a 5-HT2A receptor antagonist, did not have any effect on
      the amitriptyline-induced ERK activation. Thus, GDNF production by amitriptyline
      was independent of monoamine. Both of the amitriptyline-induced ERK activation
      and GDNF mRNA expression were blocked by genistein, a general protein tyrosine
      kinase (PTK) inhibitor. Actually, we found that amitriptyline acutely increased
      phosphorylation levels of several phosphotyrosine-containing proteins. Taken
      together, these findings indicate that ERK activation through PTK regulates
      antidepressant-induced GDNF production and that the GDNF production in glial
      cells may be a novel action of the antidepressant, which is independent of
      monoamine.

PMID- 17210800
TI  - The endogenous cannabinoid anandamide produces delta-9-tetrahydrocannabinol-like
      discriminative and neurochemical effects that are enhanced by inhibition of fatty
      acid amide hydrolase but not by inhibition of anandamide transport.
AB  - Anandamide is an endogenous ligand for brain cannabinoid CB(1) receptors, but its
      behavioral effects are difficult to measure due to rapid inactivation. Here we
      used a drug-discrimination procedure to test the hypothesis that anandamide,
      given i.v. or i.p., would produce discriminative effects like those of delta-9
      tetrahydrocannabinol (THC) in rats when its metabolic inactivation was inhibited.
      We also used an in vivo microdialysis procedure to investigate the effects of
      anandamide, given i.v. or i.p., on dopamine levels in the nucleus accumbens shell
      in rats. When injected i.v., methanandamide (AM-356), a metabolically stable
      anandamide analog, produced clear dose-related THC-like discriminative effects,
      but anandamide produced THC-like discriminative effects only at a high 10-mg/kg
      dose that almost eliminated lever-press responding. Cyclohexyl carbamic acid 3'
      carbamoyl-biphenyl-3-yl ester (URB-597), an inhibitor of fatty acid amide
      hydrolase (FAAH), the main enzyme responsible for metabolic inactivation of
      anandamide, produced no THC-like discriminative effects alone but dramatically
      potentiated discriminative effects of anandamide, with 3 mg/kg anandamide
      completely substituting for the THC training dose. URB-597 also potentiated the
      ability of anandamide to increase dopamine levels in the accumbens shell. The THC
      like discriminative-stimulus effects of anandamide after URB-597 and
      methanandamide were blocked by the CB1 receptor antagonist rimonabant, but not
      the vanilloid VR1 receptor antagonist capsazepine. Surprisingly, the anandamide
      transport inhibitors N-(4-hydroxyphenyl)-eicosa-5,8,11,14-tetraenamide (AM-404)
      and N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide (UCM-707) did not potentiate
      THC-like discriminative effects of anandamide or its dopamine-elevating effects.
      Thus, anandamide has THC-like discriminative and neurochemical effects that are
      enhanced after treatment with a FAAH inhibitor but not after treatment with
      transport inhibitors, suggesting brain area specificity for FAAH versus
      transport/FAAH inactivation of anandamide.

PMID- 17210801
TI  - Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive
      decline in nondemented older adults.
AB  - OBJECTIVES: To investigate the ability of cerebrospinal fluid (CSF) and plasma
      measures to discriminate early-stage Alzheimer disease (AD) (defined by clinical
      criteria and presence/absence of brain amyloid) from nondemented aging and to
      assess whether these biomarkers can predict future dementia in cognitively normal
      individuals. DESIGN: Evaluation of CSF beta-amyloid(40) (Abeta(40)), Abeta(42),
      tau, phosphorylated tau(181), and plasma Abeta(40) and Abeta(42) and longitudinal
      clinical follow-up (from 1 to 8 years). SETTING: Longitudinal studies of healthy
      aging and dementia through an AD research center. PARTICIPANTS: Community
      dwelling volunteers (n = 139) aged 60 to 91 years and clinically judged as
      cognitively normal (Clinical Dementia Rating [CDR], 0) or having very mild (CDR,
      0.5) or mild (CDR, 1) AD dementia. RESULTS: Individuals with very mild or mild AD
      have reduced mean levels of CSF Abeta(42) and increased levels of CSF tau and
      phosphorylated tau(181). Cerebrospinal fluid Abeta(42) level completely
      corresponds with the presence or absence of brain amyloid (imaged with Pittsburgh
      Compound B) in demented and nondemented individuals. The CSF tau/Abeta(42) ratio
      (adjusted hazard ratio, 5.21; 95% confidence interval, 1.58-17.22) and
      phosphorylated tau(181)/Abeta(42) ratio (adjusted hazard ratio, 4.39; 95%
      confidence interval, 1.62-11.86) predict conversion from a CDR of 0 to a CDR
      greater than 0. CONCLUSIONS: The very mildest symptomatic stage of AD exhibits
      the same CSF biomarker phenotype as more advanced AD. In addition, levels of CSF
      Abeta(42), when combined with amyloid imaging, augment clinical methods for
      identifying in individuals with brain amyloid deposits whether dementia is
      present or not. Importantly, CSF tau/Abeta(42) ratios show strong promise as
      antecedent (preclinical) biomarkers that predict future dementia in cognitively
      normal older adults.

PMID- 17210803
TI  - The interplay of age, access to health care, and insurance status: the good, the
      bad, and the ugly.

PMID- 17210804
TI  - Progranulin and tau gene mutations both as cause for dementia: 17q21 finally
      defined.

PMID- 17210805
TI  - Circuits and circuit disorders of the basal ganglia.
AB  - Views of the anatomy and function of the basal ganglia and their role in motor
      and nonmotor disorders have undergone major revisions during the past decades.
      The basal ganglia are now appreciated as components of parallel, reentrant
      cortico-subcortical circuits, which originate from individual cortical areas,
      traverse the basal ganglia and thalamus, and terminate in their respective areas
      of origin in the frontal lobe. Further research and clinical experience have
      resulted in new insights and perspectives on the details of the circuitry and on
      the role of these structures in Parkinson disease and other basal ganglia
      disorders. On the basis of anatomical and physiological studies and the striking
      success of focused surgical interventions, it seems appropriate to view these
      varied clinical disorders as circuit disorders, resulting from pathologic
      disturbances in neuronal activity throughout specific cortico-subcortical loops.

PMID- 17210806
TI  - Trigeminal autonomic cephalgias due to structural lesions: a review of 31 cases.
AB  - Trigeminal autonomic cephalgias (TACs) include cluster headache, paroxysmal
      hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival
      injection and tearing. Associated structural lesions may be found, but a causal
      relationship is often difficult to establish. We sought to identify clinical
      predictors of underlying structural abnormalities by reviewing previously
      described and new TAC and TAC-like cases associated with a structural lesion. We
      found that even typical TACs can be caused by an underlying lesion. Clinical
      warning signs and symptoms are relatively rare. We recommend neuroimaging in all
      patients with a TAC or TAC-like syndrome.

PMID- 17210807
TI  - Progranulin mutations in primary progressive aphasia: the PPA1 and PPA3 families.
AB  - BACKGROUND: Primary progressive aphasia (PPA) is a language-based dementia
      characterized by fluent or nonfluent language disorder as its principal feature.
      OBJECTIVE: To describe progranulin gene mutations in 2 families with PPA. DESIGN:
      Report of affected families. SETTING: Academic research. PATIENTS: Two families,
      PPA1 and PPA3, were studied. Genomic DNA was isolated from 3 of 4 siblings in
      PPA1, from all 3 siblings in PPA3, and from more than 200 control subjects. MAIN
      OUTCOME MEASURES: All 12 coding exons of the progranulin gene and the 5" and 3"
      untranslated regions were amplified by polymerase chain reaction and were
      sequenced in both directions using relevant primers. RESULTS: Both affected
      members of PPA1 for whom DNA was available and both affected sisters of PPA3 had
      a progranulin gene mutation not found in the unaffected siblings or in the
      controls. The mutations likely cause a null allele and a reduction in the level
      of functional progranulin protein. Both affected members of PPA1 with autopsies
      had frontotemporal lobar degeneration with tau-negative ubiquinated inclusions.
      CONCLUSIONS: To our knowledge, these are the only known families in which
      affected members display phenotypical homogeneity for PPA in the initial stages
      of the disease. In both families, the disease segregated with progranulin gene
      mutations. Whether progranulin dysfunction also extends to sporadic PPA and how
      it affects the initial anatomical specificity of neurodegeneration remain to be
      determined.

PMID- 17210808
TI  - Early recurrent ischemic lesions on diffusion-weighted imaging in symptomatic
      intracranial atherosclerosis.
AB  - BACKGROUND: Prior observations have shown that early recurrent ischemic lesions
      (ERILs) on diffusion-weighted imaging occur frequently within the first week
      after an index stroke. OBJECTIVE: To investigate differential patterns of ERILs
      among stroke subtypes, particularly intracranial large-artery atherosclerosis (IC
      LAA). DESIGN: Retrospective study. SETTING: Tertiary university hospital.
      PATIENTS: We included 133 patients who experienced an acute ischemic stroke and
      who underwent initial diffusion-weighted imaging within 24 hours and subsequent
      diffusion-weighted imaging within 7 days after onset, and whose stroke subtype
      was IC-LAA, extracranial LAA (EC-LAA), or cardioembolism (CE). MAIN OUTCOME
      MEASURE: Early recurrent ischemic lesions were defined as new ischemic lesions on
      follow-up diffusion-weighted imaging, separate from the index stroke lesion.
      RESULTS: Early recurrent ischemic lesions were observed in the following
      proportions: 50.9% (28/55) in the IC-LAA group, 47.4% (9/19) in the EC-LAA group,
      and 44.1% (26/59) in the CE group. Early recurrent ischemic lesions in the IC-LAA
      group had the following characteristics: (1) they occurred mostly (27 [96.4%] of
      28) in the pial area of the same vascular territory as the index stroke; (2) they
      were more frequently observed in a higher grade of stenosis than in milder
      stenosis (P<.001), whereas ERILs in the EC-LAA group were not related to the
      degree of stenosis; (3) they were not associated with subsequent recanalization,
      whereas ERILs in the CE group were mostly associated with subsequent
      recanalization (P<.001); and (4) they were more closely associated with clinical
      recurrence than in the EC-LAA or CE group (P=.02). CONCLUSION: Early recurrent
      ischemic lesions in the IC-LAA group are relatively frequent and have different
      patterns than in the EC-LAA or CE group.

PMID- 17210809
TI  - Dysphagia in patients with frontotemporal lobar dementia.
AB  - BACKGROUND: Hyperorality, compulsive eating and aspiration because of food
      gorging, has been described in patients with frontotemporal lobar dementia
      (FTLD), but swallowing function in this population has not been reported.
      OBJECTIVE: To identify the swallowing status in a sample of patients with FTLD.
      DESIGN: Case series. SETTING: Referral center, ambulatory care. PATIENTS: A
      consecutive series of referred patients with 3 variants of FTLD were asked to
      participate. Twenty-one patients were enrolled, including 9 with frontotemporal
      dementia, 7 with progressive nonfluent aphasia, and 5 with semantic dementia.
      INTERVENTION: The patients underwent a fiberoptic endoscopic examination of
      swallowing to assess their ability to swallow liquids and food. MAIN OUTCOME
      MEASURES: Presence of dysphagia and nature of impaired swallowing. RESULTS: Of
      the 21 patients, 4 caretakers reported swallowing difficulties. An instrumental
      examination revealed moderate swallowing abnormalities in 12 of the 21 patients.
      These abnormalities were not explained by compulsive eating behaviors, but seemed
      to reflect deficits in cortical and subcortical pathways connecting with the
      brainstem swallowing center. CONCLUSIONS: When assessed via instrumentation,
      swallowing abnormalities are found in many patients with FTLD. The appearance of
      dysphagia signals progression of FTLD to brainstem systems.

PMID- 17210810
TI  - The association between H63D mutations in HFE and amyotrophic lateral sclerosis
      in a Dutch population.
AB  - BACKGROUND: Mutations in HFE, a gene defect that can disrupt iron metabolism,
      have been implicated in increasing the risk of developing amyotrophic lateral
      sclerosis (ALS). OBJECTIVE: To further establish the association between ALS and
      HFE mutations by investigating whether HFE mutations are associated with an
      increased risk of developing ALS in a population in The Netherlands and by
      pooling our results with those from previous studies. DESIGN: Retrospective
      study. SETTING: Tertiary referral center for neuromuscular disorders.
      PARTICIPANTS: Genotyping for 2 common HFE mutations was performed in 289 patients
      with ALS and 5886 population-based controls in The Netherlands between January 1,
      2000, and December 31, 2004. MAIN OUTCOME MEASURES: Development of ALS and
      clinical phenotype were compared among the different HFE genotypes, adjusting for
      known prognostic factors such as age at onset and sex. RESULTS: Homozygosity for
      H63D was associated with an increased risk of developing ALS (odds ratio [OR],
      2.2; 95% confidence interval [CI], 1.1-4.1). After pooling our results with those
      from previous studies, a positive association between H63D homozygotes (OR, 2.7;
      95% CI, 1.7-4.4), heterozygotes (OR, 1.5; 95% CI, 1.0-2.1), and mutation carriers
      (OR, 1.7; 95% CI, 1.1-2.5) was found. Within the patient group, heterozygosity
      for the H63D mutation was associated with a higher age at onset. CONCLUSIONS:
      These findings suggest that H63D mutations in HFE play a role in the pathogenesis
      of ALS in various populations. This association might involve a later-onset
      subset of ALS.

PMID- 17210811
TI  - Multiple sclerosis after infectious mononucleosis.
AB  - BACKGROUND: Infectious mononucleosis caused by the Epstein-Barr virus has been
      associated with increased risk of multiple sclerosis. However, little is known
      about the characteristics of this association. OBJECTIVE: To assess the
      significance of sex, age at and time since infectious mononucleosis, and attained
      age to the risk of developing multiple sclerosis after infectious mononucleosis.
      DESIGN: Cohort study using persons tested serologically for infectious
      mononucleosis at Statens Serum Institut, the Danish Civil Registration System,
      the Danish National Hospital Discharge Register, and the Danish Multiple
      Sclerosis Registry. SETTING: Statens Serum Institut. PATIENTS: A cohort of 25 234
      Danish patients with mononucleosis was followed up for the occurrence of multiple
      sclerosis beginning on April 1, 1968, or January 1 of the year after the
      diagnosis of mononucleosis or after a negative Paul-Bunnell test result,
      respectively, whichever came later and ending on the date of multiple sclerosis
      diagnosis, death, emigration, or December 31, 1996, whichever came first. MAIN
      OUTCOME MEASURE: The ratio of observed to expected multiple sclerosis cases in
      the cohort (standardized incidence ratio). RESULTS: A total of 104 cases of
      multiple sclerosis were observed during 556,703 person-years of follow-up,
      corresponding to a standardized incidence ratio of 2.27 (95% confidence interval,
      1.87-2.75). The risk of multiple sclerosis was persistently increased for more
      than 30 years after infectious mononucleosis and uniformly distributed across all
      investigated strata of sex and age. The relative risk of multiple sclerosis did
      not vary by presumed severity of infectious mononucleosis. CONCLUSIONS: The risk
      of multiple sclerosis is increased in persons with prior infectious
      mononucleosis, regardless of sex, age, and time since infectious mononucleosis or
      severity of infection. The risk of multiple sclerosis may be increased soon after
      infectious mononucleosis and persists for at least 30 years after the infection.

PMID- 17210812
TI  - Lack of correlation between cortical demyelination and white matter pathologic
      changes in multiple sclerosis.
AB  - BACKGROUND: Histopathologic studies have shown that subpial cortical
      demyelination is extensive in chronic multiple sclerosis (MS). OBJECTIVE: To
      study whether subpial cortical demyelination in MS is associated with focal or
      diffuse white matter (WM) pathologic features on magnetic resonance imaging (MR
      imaging). DESIGN: Comparison of postmortem MR imaging findings with
      histopathologic findings. SETTING: Brain donations from a general community.
      PATIENTS: Three patients with MS with extensive cortical demyelination and 3
      patients with minor cortical demyelination were selected from an MS autopsy data
      set. The postmortem MR imaging and histopathologic data of the patients were
      compared. MAIN OUTCOME MEASURES: Two observers blinded to the results of each
      other assessed the presence, extent, and distribution of focal and diffuse
      pathologic changes in WM by MR imaging and by histopathology. RESULTS: Extensive
      subpial demyelination was not associated with a significant increase in the area
      of focal and diffuse WM pathologic changes as assessed by Luxol fast blue
      histochemistry or by MR imaging or with the presence or extent of juxtacortical
      abnormalities on MR imaging. CONCLUSIONS: The lack of association of MS gray
      matter demyelination with diffuse or focal WM changes indicates that gray matter
      demyelination in MS occurs largely independent of WM pathologic changes. The
      extent or distribution of WM abnormalities cannot be used to identify extensive
      cortical demyelination in the clinical setting.

PMID- 17210813
TI  - Relation of higher folate intake to lower risk of Alzheimer disease in the
      elderly.
AB  - BACKGROUND: Higher intake of folate and vitamins B6 (pyridoxine hydrochloride)
      and B12 (cyanocobalamin) may decrease the risk of Alzheimer disease (AD) through
      the lowering of homocysteine levels. OBJECTIVE: To relate intake of folate and
      vitamins B6 and B12 to AD risk. DESIGN AND PATIENTS: We followed up 965 persons
      65 years or older without dementia at baseline for a mean +/- SD period of 6.1 +/
      3.3 person-years after the administration of a semiquantitative food frequency
      questionnaire. Total, dietary, and supplement intake of folate and vitamins B6
      and B12 and kilocalorie intake were estimated from the questionnaire responses.
      We related energy-adjusted intake of folate and vitamins B6 and B12 to incident
      AD using the Cox proportional hazards regression model. MAIN OUTCOME MEASURE:
      Incident AD. RESULTS: We found 192 cases of incident AD. The highest quartile of
      total folate intake was related to a lower risk of AD (hazard ratio, 0.5; 95%
      confidence interval, 0.3-0.9; P=.02 for trend) after adjustment for age, sex,
      education, ethnic group, the epsilon4 allele of apolipoprotein E, diabetes
      mellitus, hypertension, current smoking, heart disease, stroke, and vitamin B6
      and B12 levels. Vitamin B6 and B12 levels were not related to the risk of AD.
      CONCLUSIONS: Higher folate intake may decrease the risk of AD independent of
      other risk factors and levels of vitamins B6 and B12. These results require
      confirmation with clinical trials.

PMID- 17210814
TI  - The metabolic syndrome and Alzheimer disease.
AB  - BACKGROUND: The metabolic syndrome is a risk factor for cardiovascular diseases,
      which have been linked to Alzheimer disease. However, a link between Alzheimer
      disease and the metabolic syndrome has not yet been established. OBJECTIVE: To
      investigate the relationship between the metabolic syndrome and Alzheimer
      disease. DESIGN, SETTING, AND PARTICIPANTS: Case-control study of 50 consecutive
      patients diagnosed with probable Alzheimer disease from the Memory Disorders
      Clinics, Launceston, Australia, and Bristol, England, and 75 cognitively normal
      controls. MAIN OUTCOME MEASURES: The odds ratio of the metabolic syndrome as
      defined by the National Cholesterol Education Program Adult Treatment Panel III.
      RESULTS: Compared with controls, patients with Alzheimer disease had a
      significantly larger mean waist circumference, higher mean plasma concentrations
      of triglycerides and glucose, and a lower mean plasma concentration of high
      density lipoprotein cholesterol, but they had lower mean systolic blood pressure.
      The metabolic syndrome was associated with Alzheimer disease (odds ratio, 3.2;
      95% confidence interval, 1.2-8.4; P = .02), and this association was strengthened
      when the hypertension component was excluded (odds ratio, 7.0; 95% confidence
      interval, 2.7-18.3; P < .001). All of the analyses were adjusted for age, sex,
      and location. CONCLUSIONS: This study suggests that Alzheimer disease is
      associated with the metabolic syndrome. This could have implications for the
      prevention and treatment of Alzheimer disease.

PMID- 17210815
TI  - An evaluation of neurocognitive status and markers of immune activation as
      predictors of time to death in advanced HIV infection.
AB  - BACKGROUND: Several markers of immune activation have been identified as
      potential prognostic markers for human immunodeficiency virus (HIV)-associated
      morbidity and mortality, but the results from studies are conflicting. OBJECTIVE:
      To evaluate whether neurocognitive status and baseline levels of plasma and
      cerebrospinal fluid tumor necrosis factor alpha (TNF-alpha), macrophage
      chemoattractant protein 1 (MCP-1), matrix metalloproteinase 2 (MMP-2), or
      macrophage colony-stimulating factor (M-CSF) are associated with time to death in
      a cohort with advanced HIV infection. DESIGN: Cohort study. SETTING: Enrollees in
      the Northeast AIDS Dementia Study. PARTICIPANTS: Three hundred twenty-nine
      subjects who were positive for HIV-1 and had a CD4 cell count of less than
      200/microL (or <300/microL but with cognitive impairment at baseline) were
      assessed for CD4 cell count, neurocognitive status, pertinent demographic and
      clinical variables, and plasma and cerebrospinal fluid HIV RNA, TNF-alpha, MCP-1,
      MMP-2, and M-CSF levels. MAIN OUTCOME MEASURES: Cox proportional hazards
      regression models were used to examine the associations between the variables of
      interest (using time-dependent covariates, where applicable) and time to death,
      adjusting for possible confounders. RESULTS: There were 50 deaths in the cohort
      after a median of 25.2 months of follow-up. The cumulative incidences of death
      were 7% at 1 year and 16% at 2 years. In Cox proportional hazards regression
      analyses adjusting for demographic, clinical, and immunological variables, HIV
      associated dementia (hazard rate, 6.10; P = .001) was significantly associated
      with time to death; (log) plasma MCP-1 level (hazard rate, 3.38; P = .08) trended
      toward significance. CONCLUSION: In patients with advanced HIV infection, HIV
      associated dementia is an independent predictor of time to death.

PMID- 17210816
TI  - Twenty-six-year change in total cholesterol levels and incident dementia: the
      Honolulu-Asia Aging Study.
AB  - BACKGROUND: The relationship between total cholesterol levels and dementia is
      unclear. OBJECTIVE: To compare the natural history of change in total cholesterol
      across 26 years between men who did and did not develop dementia 3 years after
      the last measurement. DESIGN, SETTING, AND PARTICIPANTS: In the Honolulu-Asia
      Aging Study, 1027 Japanese American men had total cholesterol levels assayed on 5
      occasions between 1965 and 1993 and were screened for dementia on 2 occasions
      between 1991 and 1996. MAIN OUTCOME MEASURE: The slope of 26-year change in serum
      total cholesterol levels was estimated by a repeated-measures analysis and was
      compared between men with incident dementia (n = 56) and those without dementia
      (n = 971) at the end of the follow-up period. RESULTS: Cholesterol levels in men
      with dementia and, in particular, those with Alzheimer disease had declined at
      least 15 years before the diagnosis and remained lower than cholesterol levels in
      men without dementia throughout that period. The difference in slopes was robust
      to adjustment for potential confounding factors, including vascular risk factors,
      weight change, alcohol intake, and use of lipid-lowering agents. CONCLUSION: A
      decline in serum total cholesterol levels may be associated with early stages in
      the development of dementia.

PMID- 17210817
TI  - Qualitative estimates of medial temporal atrophy as a predictor of progression
      from mild cognitive impairment to dementia.
AB  - BACKGROUND: Individuals diagnosed as having mild cognitive impairment (MCI) have
      a high likelihood of progressing to dementia within 3 to 5 years, but not all
      individuals with MCI progress to dementia. Prognostic uncertainty suggests the
      need for additional measures to assist the clinician. OBJECTIVE: To assess the
      added value of qualitative measures of medial temporal atrophy (MTA) to estimate
      the relative risk of progressing from MCI to dementia. DESIGN: A 3-year, double
      blind, placebo-controlled Alzheimer's Disease Cooperative Study initially
      designed to evaluate the efficacy of donepezil hydrochloride or vitamin E vs
      placebo to delay progression of MCI to dementia. SETTING: Memory assessment
      centers. PATIENTS: A total of 190 individuals with MCI. MAIN OUTCOME MEASURES:
      Ratings of MTA performed using magnetic resonance images obtained at baseline.
      Log-rank tests and Cox proportional hazards ratios examining the significance of
      MTA estimates in predicting progression of MCI to dementia. RESULTS: A mean MTA
      score greater than 2.0 was associated with a greater than 2-fold increased
      likelihood of progression to dementia during the observation period (hazards
      ratio, 2.30; 95% confidence interval, 1.09-4.92; P = .03) after controlling for
      age, education, sex, and baseline Mini-Mental State Examination score.
      CONCLUSIONS: Adjusted estimates of MTA were associated with significantly
      increased risk of developing dementia within 3 years, suggesting that obtaining a
      magnetic resonance image during the evaluation of MCI may offer additional
      independent information about the risk of progression to dementia. Given the
      relatively high prevalence of MCI in the general population, use of this method
      as part of routine clinical evaluation may help identify individuals who might
      benefit from increased surveillance and future treatment. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00000173.

PMID- 17210818
TI  - Specific psychiatric manifestations among preclinical Huntington disease mutation
      carriers.
AB  - BACKGROUND: Despite the need for significant clinical intervention owing to the
      psychiatric manifestations of Huntington disease (HD), there has been a paucity
      of studies specifically designed to evaluate these symptoms prior to disease
      diagnosis. OBJECTIVES: To investigate whether the Symptom Checklist 90-Revised
      (SCL-90-R) and the Center for Epidemiological Studies Depression Scale can be
      used to detect psychiatric manifestations among preclinical mutation carriers
      with absent or minimal motor signs of HD. DESIGN, SETTING, AND PARTICIPANTS:
      Individuals at risk for or recently diagnosed with HD were recruited and then
      evaluated at Indiana University School of Medicine, Indianapolis. All of the
      subjects completed a uniform clinical evaluation that included the Unified
      Huntington's Disease Rating Scale-99, molecular testing to determine HD mutation
      status, the SCL-90-R, and the Center for Epidemiological Studies Depression
      Scale. The sample was divided into 4 study groups: 171 individuals in the
      nonmutation carrier group; 29 with minimal, if any, motor signs of HD in the
      preclinical mutation carrier group 1; 20 with motor abnormalities suggestive of
      HD in the preclinical mutation carrier group 2; and 34 in the manifest HD group.
      MAIN OUTCOME MEASURES: Scores on the SCL-90-R and Center for Epidemiological
      Studies Depression Scale were compared. RESULTS: Five SCL-90-R symptom dimensions
      (obsessive-compulsive, interpersonal sensitivity, anxiety, paranoid ideation, and
      psychoticism) demonstrated a significant group effect (P < or = .04). The
      preclinical mutation carrier group 2 and the manifest HD group scored
      significantly higher on all 5 dimensions as compared with the nonmutation carrier
      group. The preclinical mutation carrier group 2 scored significantly higher than
      the nonmutation carrier group for 3 of the SCL-90-R symptom dimensions (anxiety,
      paranoid ideation, and psychoticism). A significant group effect was found on the
      Center for Epidemiological Studies Depression Scale (P = .04). The frequency of
      depressive symptoms was significantly higher in the manifest HD group and the
      preclinical mutation carrier group 2 as compared with the nonmutation carrier
      group. CONCLUSION: This study identified specific psychiatric symptom dimensions
      that differentiate nonmutation carriers from individuals in the early preclinical
      stages of HD who are either symptom free or have minor nonspecific motor
      abnormalities.

PMID- 17210820
TI  - Ornithine transcarbamylase deficiency presenting as encephalopathy during
      adulthood following bariatric surgery.
AB  - BACKGROUND: Neurological complications following bariatric surgery are rare.
      Whereas nutritional deficiencies are the most common cause of neurological
      symptoms, the unmasking of previously subclinical metabolic disorders can also
      lead to significant morbidity. OBJECTIVE: To characterize the clinical
      presentation, serum biochemical fluctuations, and functional enzymatic analysis
      of a case of functional ornithine transcarbamylase deficiency unmasked by a
      dietary change following bariatric surgery. DESIGN: Case report. SETTING:
      Tertiary referral center, hospital (inpatient) setting. PATIENT: A 29-year-old
      woman who presented with intermittent encephalopathy associated with recurrent
      hyperammonemia. INTERVENTIONS: Clinical, biochemical, and mutational studies.
      RESULTS: The pattern of intermittent hyperammonemia and encephalopathy following
      oral and parenteral nutrition suggested a urea cycle abnormality. Functional
      enzymatic assay results showed markedly reduced ornithine transcarbamylase
      activity in the absence of known coding mutations. CONCLUSION: Previously
      asymptomatic ornithine transcarbamylase deficiency should be suspected in adult
      patients who develop recurrent hyperammonemia and encephalopathy following
      bariatric surgery.

PMID- 17210819
TI  - Cerebral salt-wasting syndrome in a patient with neuroleptic malignant syndrome.
AB  - BACKGROUND: Hyponatremia associated with neuroleptic malignant syndrome has thus
      far been described as a syndrome of inappropriate secretion of antidiuretic
      hormone. OBJECTIVES: To ascertain and describe the role of cerebral salt-wasting
      syndrome as the cause of hyponatremia in a patient with neuroleptic malignant
      syndrome. PATIENT: A psychotic patient being treated with olanzapine presenting
      with sopor, muscle rigidity, polyuria, tachycardia, pyrexia, and severe
      hyponatremia. METHODS: Serial serological examinations of plasma tonicity (sodium
      level and osmolality), brain natriuretic peptide, and antidiuretic hormone were
      performed, and sodium excretion and urine osmolality were determined from 24-hour
      urine collection. In addition, markers for rhabdomyolysis were monitored.
      RESULTS: The patient shows clear symptoms of cerebral salt-wasting syndrome in
      association with neuroleptic malignant syndrome, characterized by severe
      hyponatremia, volume depletion, and elevated brain natriuretic peptide but normal
      antidiuretic hormone levels. Cerebral salt-wasting syndrome improved under
      dantrolene sodium treatment and concomitant fluid and sodium replacement.
      CONCLUSION: Hyponatremia in patients with neuroleptic malignant syndrome might
      more likely reflect cerebral salt-wasting syndrome than a syndrome of
      inappropriate secretion of antidiuretic hormone as an additional aspect of
      autonomic dysregulation caused by antidopaminergic drugs.

PMID- 17210821
TI  - Sarcoid meningitis with fulminant delirium and markedly abnormal cerebrospinal
      fluid.
AB  - OBJECTIVE: To describe a patient with an acute fulminant delirium and eventual
      spinal fluid block secondary to sarcoid meningitis. DESIGN: Case report. SETTING:
      Hospital and Neurology Clinic. PATIENT: A previously healthy, 24-year-old man.
      INTERVENTIONS: Antimicrobials, corticosteroids, lumbar puncture, myelography, and
      lymph node biopsy. MAIN OUTCOME MEASURES: Cerebrospinal fluid, clinical status.
      RESULTS: The patient improved after treatment with corticosteroids. CONCLUSION:
      Sarcoid meningitis may present with delirium and spinal block.

PMID- 17210822
TI  - Involvement of the septum pellucidum and intracranial vessel in neurosarcoidosis.

PMID- 17210823
TI  - Rhizomycosis infection in the basal ganglia.

PMID- 17210824
TI  - Pathophysiology of motor complications in Parkinson disease: postsynaptic
      mechanisms are crucial.

PMID- 17210825
TI  - Presynaptic mechanisms of motor complications in Parkinson disease.

PMID- 17210826
TI  - Both postsynaptic and presynaptic dysfunction contribute to Parkinson disease:
      any mechanism will not do.

PMID- 17210827
TI  - Increase of disease duration of amyotrophic lateral sclerosis in a mouse model by
      transgenic small interfering RNA.

PMID- 17210828
TI  - Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with
      a history of preeclampsia.
AB  - Activating angiotensin II type 1 autoantibodies (AT1-AAs) develop in women with
      preeclampsia and may contribute to the disorder. Insulin resistance and serum
      concentrations of the antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt-1)
      are also increased in women with preeclampsia compared with normal pregnancy.
      sFlt-1 and insulin resistance decrease substantially after delivery; however,
      significant group differences persist postpartum. Women who have had preeclampsia
      are at increased cardiovascular risk later in life. We measured AT1-AAs in groups
      of women with previous preeclampsia (n=29) and previous normal pregnancies (n=35)
      18+/-9 months after the first completed pregnancy. These women had had sFlt-1,
      insulin resistance homeostasis model assessment score, and related cardiovascular
      risk factors measured. Activating antibodies were detected by the chronotropic
      response of cultured neonatal rat cardiomyocytes coupled with receptor-specific
      antagonists (losartan and prazosin). AT1-AAs were detected in 17.2% of women with
      previous preeclampsia versus 2.9% of women with previous uncomplicated
      pregnancies (P<0.05). In contrast, there was no difference in the prevalence of
      autoantibodies against the alpha1-adrenoceptor (10% of previous preeclamptic
      versus 14% of previous normal pregnant). Women with activating autoantibodies had
      significantly increased sFlt-1, reduced free vascular endothelial growth factor,
      and higher insulin resistance homeostasis model assessment values compared with
      autoantibody-negative women. These data suggest that, as with sFlt-1 and insulin
      resistance, the AT1-AA does not regress completely after delivery and,
      secondarily, that correlations exist among these variables. The impact of AT1-AA
      after preeclampsia, especially in the context of cardiovascular risk, remains to
      be determined.

PMID- 17210829
TI  - Excessive sympathetic activation in heart failure with obesity and metabolic
      syndrome: characteristics and mechanisms.
AB  - Congestive heart failure is characterized by sympathetic activation, which has
      also been described in the metabolic syndrome. No information exists, however, as
      to whether the sympathostimulating effects of these 2 conditions summate when
      heart failure is complicated by the metabolic syndrome, leading to an exceedingly
      high adrenergic drive. This is clinically relevant, because in heart failure
      sympathetic activation is closely related to mortality. We studied 48 control
      subjects (age: 58.4+/-1.6 years, mean+/-SEM) and 89 age-matched heart failure
      patients (New York Heart Association class II), of whom 47 were without and 42
      were with metabolic syndrome. Measurements included blood pressure (Finapres),
      heart rate (ECG), and sympathetic nerve traffic (microneurography) at rest and
      during baroreceptor manipulation. Waist circumference, blood pressure, and
      metabolic variables were greater in heart failure with metabolic syndrome than in
      heart failure without metabolic syndrome and in control subjects. Left
      ventricular ejection fraction and end-diastolic diameter were similarly altered
      in the 2 heart failure groups. Compared with control subjects, sympathetic nerve
      activity was greater in heart failure patients without metabolic syndrome (64.7+/
      3.2 versus 45.8+/-2.9 bursts/100 heartbeats; P<0.01), a further pronounced
      increase being detected in those with metabolic syndrome (80.9+/-3.2 bursts/100
      heartbeats; P<0.01). In the multivariate analysis, waist circumference and body
      mass index were the variables most closely related to sympathetic activation.
      Compared with control subjects, baroreflex responses were significantly
      attenuated in the 2 heart failure groups, the impairment being more marked in the
      group with than without metabolic syndrome. Thus, obesity and metabolic syndrome
      potentiate the sympathetic activation characterizing heart failure. This
      potentiation is likely to mainly depend on metabolic and baroreflex mechanisms.

PMID- 17210830
TI  - Mechanism of endothelial nitric oxide synthase phosphorylation and activation by
      thrombin.
AB  - Thrombin has been shown to activate endothelial NO synthase (eNOS) leading to
      endothelium-dependent vasorelaxation. In addition to its activation by
      Ca2+/calmodulin, eNOS has several regulatory sites. Ser1179 phosphorylation of
      eNOS by the phosphatidylinositol 3-kinase-dependent Akt stimulates its catalytic
      activity. In this study, we have elucidated the signaling mechanism of thrombin
      induced phosphorylation of eNOS in the regulation of NO production. Immunoblot
      analysis showed that thrombin rapidly phosphorylates eNOS at Ser1179 in cultured
      bovine aortic endothelial cells. Also, thrombin was unable to stimulate eNOS if
      the Ser1179 was mutated to Ala. Akt is phosphorylated in response to thrombin at
      Ser473 at a later time point than eNOS. In this regard, a phosphatidylinositol 3
      kinase inhibitor, LY294002, blocked Akt phosphorylation without affecting eNOS
      phosphorylation and cGMP production by thrombin. The Ca2+ ionophore A23187
      stimulated eNOS phosphorylation, as well as cGMP production, and pretreatment
      with intracellular or extracellular Ca2+ chelators inhibited thrombin-induced
      eNOS phosphorylation and cGMP production. Moreover, infection of bovine aortic
      endothelial cell with adenovirus encoding dominant-negative mutants of protein
      kinase C (PKC) and PKC or pretreatment of bovine aortic endothelial cells with
      PKC inhibitors revealed that PKC is indispensable for thrombin-induced eNOS
      phosphorylation and activation. From these data, we concluded that thrombin
      induces the Ser1179 phosphorylation-dependent eNOS activation through a Ca2+
      dependent, PKC-sensitive, but phosphatidylinositol 3-kinase/Akt-independent
      pathway.

PMID- 17210831
TI  - Cardiac hypertrophy and the Wnt/Frizzled pathway.

PMID- 17210832
TI  - Interruption of Wnt signaling attenuates the onset of pressure overload-induced
      cardiac hypertrophy.
AB  - The hypertrophic response of the heart has been recognized recently as the net
      result of activation of prohypertrophic and antihypertrophic pathways. Here we
      report the involvement of the Wnt/Frizzled pathway in the onset of cardiac
      hypertrophy development. Stimulation of the Wnt/Frizzled pathway activates the
      disheveled (Dvl) protein. Disheveled subsequently can inhibit glycogen synthase
      kinase-3beta, a protein with potent antihypertrophic actions through diverse
      molecular mechanisms. In the Wnt/Frizzled pathway, inhibition of glycogen
      synthase kinase-3beta leads to an increased amount of beta-catenin, which can act
      as a transcription factor for several hypertrophy-associated target genes. In
      this study we subjected mice lacking the Dvl-1 gene and their wild-type
      littermates to thoracic aortic constriction for 7, 14, and 35 days. In mice
      lacking the Dvl-1 gene, 7 days of pressure overload-induced increases in left
      ventricular posterior wall thickness and expression of atrial natriuretic factor
      and brain natriuretic protein were attenuated compared with their wild-type
      littermates. Beta-catenin protein amount was reduced in the group lacking the Dvl
      1 gene, and an increased glycogen synthase kinase-3beta activity was observed.
      Moreover, the increase in the amount of Ser(473)-phosphorylated Akt, a stimulator
      of cardiac hypertrophy, was lower in the group lacking the Dvl-1 gene. In
      conclusion, we have demonstrated that interruption of Wnt signaling in the mice
      lacking the Dvl-1 gene attenuates the onset of pressure overload-induced cardiac
      hypertrophy through mechanisms involving glycogen synthase kinase-3beta and Akt.
      Therefore, the Wnt/Frizzled pathway may provide novel therapeutic targets for
      antihypertrophic therapy.

PMID- 17210833
TI  - Gene transfer of neuronal nitric oxide synthase into intracardiac Ganglia
      reverses vagal impairment in hypertensive rats.
AB  - Hypertension is associated with reduced cardiac vagal activity and decreased
      atrial guanylate cyclase and cGMP levels. Neuronal production of NO facilitates
      cardiac parasympathetic transmission, although oxidative stress caused by
      hypertension may disrupt this pathway. We tested the hypothesis that peripheral
      vagal responsiveness is attenuated in the spontaneously hypertensive rat (SHR)
      because of impaired NO-cGMP signaling and that gene transfer of neuronal NO
      synthase (nNOS) into cholinergic intracardiac ganglia can restore neural
      function. Cardiac vagal heart rate responses in the isolated SHR atrial/right
      vagus preparation were significantly attenuated compared with age-matched
      normotensive Wistar-Kyoto rats. [(3)H] acetylcholine release was also
      significantly lower in the SHR. The NO donor, sodium nitroprusside, augmented
      vagal responses to nerve stimulation and [(3)H] acetylcholine release in the
      Wistar-Kyoto rat, whereas the soluble guanylate cyclase inhibitor 1H
      (1,2,4)oxadiazolo(4,3-a)quinoxaline-1-one attenuated [(3)H] acetylcholine release
      in Wistar-Kyoto atria. No effects of sodium nitroprusside or 1H
      (1,2,4)oxadiazolo(4,3-a)quinoxaline-1-one were seen in the SHR during nerve
      stimulation. In contrast, SHR atria were hyperresponsive to carbachol-induced
      bradycardia, with elevated production of atrial cGMP. After gene transfer of
      adenoviral nNOS into the right atrium, vagal responsiveness in vivo was
      significantly increased in the SHR compared with transfection with adenoviral
      enhanced green fluorescent protein. Atrial nNOS activity was increased after gene
      transfer of adenoviral nNOS, as was expression of alpha(1)-soluble guanylate
      cyclase in both groups compared with adenoviral enhanced green fluorescent
      protein. In conclusion, a significant component of cardiac vagal dysfunction in
      hypertension is attributed to an impairment of the postganglionic presynaptic NO
      cGMP pathway and that overexpression of nNOS can reverse this neural phenotype.

PMID- 17210834
TI  - Elevations in renal interstitial hydrostatic pressure and 20
      hydroxyeicosatetraenoic acid contribute to pressure natriuresis.
AB  - This study examined the role of changes in renal interstitial pressure on the
      renal levels of cytochrome P450 metabolites of arachidonic acid and compared the
      effects of inhibition of the formation of 20-hydroxyeicosatetraenoic acid (20
      HETE) and epoxyeicosatrienoic acids with 1-aminobenzotriazole on the pressure
      natriuretic response versus that seen after administration of HET0016, a more
      selective inhibitor of the formation of 20-HETE. Renal interstitial pressure rose
      by 3.4+/-0.3 mm Hg, and the levels of 20-HETE in renal cortical tissue doubled
      when renal perfusion pressure was increased from 100 to 160 mm Hg. Removal of the
      renal capsule prevented the increase in renal interstitial pressure and 20-HETE
      levels after an elevation in renal perfusion pressure. Urine flow and sodium
      excretion increased 5-fold when renal perfusion pressure was increased from 106
      to 160 mm Hg. The administration of 1-aminobenzotriazole (50 mg/kg, IP) or
      HET0016 (10 mg/kg IV bolus plus 1 mg/kg per hour of infusion) decreased the
      pressure-natriuretic response by 50% and inhibited the renal formation of 20-HETE
      and epoxyeicosatrienoic acids by 90% and 50%, respectively. Administration of a
      lower dose of HET0016 (1 mg/kg per hour, IV) selectively reduced the formation of
      20-HETE by 80% without inhibiting renal epoxygenase activity and blunted the
      pressure-natriuretic response by 42%. These results indicate that elevations in
      renal perfusion pressure increase 20-HETE levels in the kidney secondary to a
      rise in renal interstitial pressure. They also suggest that 20-HETE, rather than
      epoxyeicosatrienoic acids, modulates the pressure-natriuretic response, because
      selective blockade of the formation of 20-HETE with HET0016 blunts the response
      to the same extent as that seen after inhibition of the formation of 20-HETE and
      epoxyeicosatrienoic acids with 1-aminobenzotriazole.

PMID- 17210835
TI  - Stress management at the worksite: reversal of symptoms profile and
      cardiovascular dysregulation.
AB  - Work stress may increase cardiovascular risk either indirectly, by inducing
      unhealthy life styles, or directly, by affecting the autonomic nervous system and
      arterial pressure. We hypothesized that, before any apparent sign of disease,
      work-related stress is already accompanied by alterations of RR variability
      profile and that a simple onsite stress management program based on cognitive
      restructuring and relaxation training could reduce the level of stress symptoms,
      revert stress-related autonomic nervous system dysregulation, and lower arterial
      pressure. We compared 91 white-collar workers, enrolled at a time of work
      downsizing (hence, in a stress condition), with 79 healthy control subjects.
      Psychological profiles were assessed by questionnaires and autonomic nervous
      system regulation by spectral analysis of RR variability. We also tested a simple
      onsite stress management program (cognitive restructuring and relaxation
      training) in a subgroup of workers compared with a sham subgroup (sham program).
      Workers presented an elevated level of stress-related symptoms and an altered
      variability profile as compared with control subjects (low-frequency component of
      RR variability was, respectively, 65.2+/-2 versus 55.3+/-2 normalized units;
      P<0.001; opposite changes were observed for the high-frequency component). These
      alterations were largely reverted (low-frequency component of RR variability from
      63.6+/-3.9 to 49.3+/-3 normalized units; P<0.001) by the stress management
      program, which also slightly lowered systolic arterial pressure. No changes were
      observed in the sham program group. This noninvasive study indicates that work
      stress is associated with unpleasant symptoms and with an altered autonomic
      profile and suggests that a stress management program could be implemented at the
      worksite, with possible preventive advantages for hypertension.

PMID- 17210836
TI  - Stopping stress at its origins.

PMID- 17210837
TI  - Regulation of endothelial nitric oxide synthase by thrombin.

PMID- 17210838
TI  - Cardiac and systemic hemodynamic characteristics of hypertension and
      prehypertension in adolescents and young adults: the Strong Heart Study.
AB  - BACKGROUND: The epidemic of overweight is increasing the prevalence of both
      prehypertension and early-onset hypertension, but few population-based data exist
      on their impact on cardiac structure and function in adolescents and young
      adults. METHODS AND RESULTS: We analyzed clinical characteristics, hemodynamic
      parameters, and left ventricular structure and function in 1940 participants, 14
      to 39 years of age, in the Strong Heart Study. Hypertension occurred in 294
      participants (15%), who were more often men (70% versus 30%), older (age, 31+/-7
      versus 25+/-8 years), and more commonly diabetic (23% versus 4.5%; all P<0.001)
      than their normotensive counterparts. Prehypertension occurred in 675 (35%) of
      participants with similar trends in gender, age, and diabetes status. After
      adjustment for covariates, both hypertensive and prehypertensive participants had
      higher left ventricular wall thickness (0.83 and 0.78 versus 0.72 cm), left
      ventricular mass (182 and 161 versus 137 g), and relative wall thickness (0.30
      and 0.29 versus 0.28 cm) and 3- and 2-fold-higher prevalences of left ventricular
      hypertrophy than their normotensive counterparts (all P<0.001). Hypertension and
      prehypertension also were associated with higher mean pulse pressure/stroke
      volume index (1.24 and 1.15 versus 1.02 mm Hg/mL x m2) and total peripheral
      resistance index (3027 and 2805 versus 2566 dynes x s x cm(-5) x m2; all
      P<0.001). CONCLUSIONS: In a population with high prevalences of obesity and
      diabetes, hypertension and prehypertension are associated with increases in both
      cardiac output and peripheral resistance index. Despite the young age of
      participants with hypertension and prehypertension, they had prognostically
      adverse preclinical cardiovascular disease, including left ventricular
      hypertrophy and evidence of increased arterial stiffness.

PMID- 17210839
TI  - Prevalence of long-QT syndrome gene variants in sudden infant death syndrome.
AB  - BACKGROUND: The hypothesis that some cases of sudden infant death syndrome (SIDS)
      could be caused by long-QT syndrome (LQTS) has been supported by molecular
      studies. However, there are inadequate data regarding the true prevalence of
      mutations in arrhythmia-susceptibility genes among SIDS cases. Given the
      importance and potential implications of these observations, we performed a study
      to more accurately quantify the contribution to SIDS of LQTS gene mutations and
      rare variants. METHODS AND RESULTS: Molecular screening of 7 genes (KCNQ1, KCNH2,
      SCN5A, KCNE1, KCNE2, KCNJ2, CAV3) associated with LQTS was performed with
      denaturing high-performance liquid chromatography and nucleotide sequencing of
      genomic DNA from 201 cases diagnosed as SIDS according to the Nordic Criteria,
      and from 182 infant and adult controls. All SIDS and control cases originated
      from the same regions in Norway. Genetic analysis was blinded to diagnosis.
      Mutations and rare variants were found in 26 of 201 cases (12.9%). On the basis
      of their functional effect, however, we considered 8 mutations and 7 rare
      variants found in 19 of 201 cases as likely contributors to sudden death (9.5%;
      95% CI, 5.8 to 14.4%). CONCLUSIONS: We demonstrated that 9.5% of cases diagnosed
      as SIDS carry functionally significant genetic variants in LQTS genes. The
      present study demonstrates that sudden arrhythmic death is an important
      contributor to SIDS. As these variants likely modify ventricular repolarization
      and QT interval duration, our results support the debated concept that an ECG
      would probably identify most infants at risk for sudden death due to LQTS either
      in infancy or later on in life.

PMID- 17210840
TI  - Cyclooxygenase-2 inhibition increases mortality, enhances left ventricular
      remodeling, and impairs systolic function after myocardial infarction in the pig.
AB  - BACKGROUND: Cyclooxygenase (COX)-2 expression in the heart increases after
      myocardial infarction (MI). In murine models of MI, COX-2 inhibition preserves
      left ventricular dimensions and function. We studied the effect of selective COX
      2 inhibition on left ventricular remodeling and function after MI in a pig model.
      METHODS AND RESULTS: Twenty-two pigs were assigned to COX-2 inhibition with a COX
      2 inhibitor (COX-2i; celecoxib 400 mg twice daily; n=14) or a control group
      (n=8). MI was induced by left circumflex coronary artery ligation, and the
      animals were euthanized 6 weeks later. Cardiac dimensions and function were
      assessed with echocardiography and conductance catheters. Infarct size and
      collagen density were analyzed with triphenyltetrazolium chloride staining and
      picrosirius red staining, respectively. COX-2 inhibition increased mortality
      compared with controls (50% versus 0%, P=0.022), whereas infarct size was similar
      (13.1+/-0.7% versus 14.1+/-0.1%, P=0.536). The decrease in thickness of the
      infarcted myocardial wall was more pronounced in the COX-2i group (60.6+/-9.6%
      versus 36.2+/-5.7%, P=0.001). End-diastolic volume was higher in the COX-2i group
      (133.9+/-33.5 versus 91.1+/-24.0 mL; P=0.021), as was the end-systolic volume at
      100 mm Hg (81.7+/-27.8 versus 56.3+/-21.1 mL; P=0.037), which indicates that
      systolic function was more severely impaired. Infarct collagen density was lower
      after COX-2i treatment (25.3+/-3.9 versus 56.1+/-23.8 gray value/mm2; P=0.005).
      CONCLUSIONS: In pigs, COX-2 inhibition after MI is associated with increased
      mortality, enhanced left ventricular remodeling, and impaired systolic function,
      probably due to decreased infarct collagen fiber density.

PMID- 17210841
TI  - Cardiac sodium channel dysfunction in sudden infant death syndrome.
AB  - BACKGROUND: Mutations in genes responsible for the congenital long-QT syndrome,
      especially SCN5A, have been identified in some cases of sudden infant death
      syndrome. In a large-scale collaborative genetic screen, several SCN5A variants
      were identified in a Norwegian sudden infant death syndrome cohort (n=201). We
      present functional characterization of 7 missense variants (S216L, R680H, T1304M,
      F1486L, V1951L, F2004L, and P2006A) and 1 in-frame deletion allele (delAL586-587)
      identified by these efforts. METHODS AND RESULTS: Whole-cell sodium currents were
      measured in tsA201 cells transiently transfected with recombinant wild-type or
      mutant SCN5A cDNA (hH1) coexpressed with the human beta1 subunit. All variants
      exhibited defects in the kinetics and voltage dependence of inactivation. Five
      variants (S216L, T1304M, F1486L, F2004L, and P2006A) exhibited significantly
      increased persistent sodium currents (range, 0.5% to 1.7% of peak current)
      typical of SCN5A mutations associated with long-QT syndrome. These same 5
      variants also displayed significant depolarizing shifts in voltage dependence of
      inactivation (range, 5 to 14 mV) and faster recovery from inactivation, but
      F1486L uniquely exhibits a depolarizing shift in the conductance-voltage
      relationship. Three alleles (delAL586-587, R680H, and V1951L) exhibited increased
      persistent current only under conditions of internal acidosis (R680H) or when
      expressed in the context of a common splice variant (delQ1077), indicating that
      they have a latent dysfunctional phenotype. CONCLUSIONS: Our present results
      greatly expand the spectrum of functionally characterized SCN5A variants
      associated with sudden infant death syndrome and provide further biophysical
      correlates of arrhythmia susceptibility in this syndrome.

PMID- 17210842
TI  - Accelerated mitochondrial adenosine diphosphate/adenosine triphosphate transport
      improves hypertension-induced heart disease.
AB  - BACKGROUND: Strong evidence suggests that mitochondrial malfunction, which leads
      to disturbed energy metabolism and stimulated apoptosis, is a linchpin in the
      induction and manifestation of cardiac failure. An adequate exchange of ATP and
      ADP over the inner mitochondrial membrane by the adenine nucleotide translocase
      (ANT) is thereby essential to guarantee the cellular energy supply. METHODS AND
      RESULTS: To explore the effect of an ameliorated mitochondrial ATP/ADP
      transportation on cardiac dysfunction, we generated transgenic rats
      overexpressing ANT1 in the heart (ANT rats) and crossed them with renin
      overexpressing rats (REN rats) suffering from hypertension-induced cardiac
      insufficiency. Cardiac-specific ANT1 overexpression resulted in a higher ATP/ADP
      transportation and elevated activities of respiratory chain complexes. Increased
      ANT activity in double-transgenic (ANT/REN) animals did not influence excessive
      hypertension seen in REN rats. Hypertension-induced cardiac hypertrophy in the
      REN rats was prevented by parallel ANT1 overexpression, however, and left
      ventricular function remarkably improved. The ANT1 overexpression led to a
      reduction in fibrosis and an improvement in cardiac tissue architecture.
      Consequently, the survival rate of ANT/REN rats was enhanced. Further
      investigations into the cardioprotective mechanism of ANT1 overexpression
      revealed improved mitochondrial structure and function and significantly reduced
      apoptosis in ANT/REN rats, shown by lowered cytosolic/mitochondrial cytochrome c
      ratio, reduced caspase 3 level, and prevented DNA degradation. CONCLUSIONS:
      Myocardial ANT1 overexpression protects against hypertension-induced cardiac
      pathology. Thus, the improvement in mitochondrial function may be a basic
      principle for new strategies in treating heart disease.

PMID- 17210846
TI  - Ophthalmic genetics: at the dawn of discovery.

PMID- 17210844
TI  - Congenital heart disease in the general population: changing prevalence and age
      distribution.
AB  - BACKGROUND: Empirical data on the changing epidemiology of congenital heart
      disease (CHD) are scant. We determined the prevalence, age distribution, and
      proportion of adults and children with severe and other forms of CHD in the
      general population from 1985 to 2000. METHODS AND RESULTS: Where healthcare
      access is universal, we used administrative databases that systematically
      recorded all diagnoses and claims. Diagnostic codes conformed to the
      International Classification of Disease, ninth revision. Severe CHD was defined
      as tetralogy of Fallot, truncus arteriosus, transposition complexes, endocardial
      cushion defects, and univentricular heart. Prevalence of severe and other CHD
      lesions was determined in 1985, 1990, 1995, and 2000 using population numbers in
      Quebec. Children were subjects <18 years of age. The prevalence was 4.09 per 1000
      adults in the year 2000 for all CHD and 0.38 per 1000 (9%) for those with severe
      lesions. Female subjects accounted for 57% of the adult CHD population. The
      median age of all patients with severe CHD was 11 years (interquartile range, 4
      to 22 years) in 1985 and 17 years (interquartile range, 10 to 28 years) in 2000
      (P<0.0001). The prevalence of severe CHD increased from 1985 to 2000, but the
      increase in adults was significantly higher than that observed in children. In
      the year 2000, 49% of those alive with severe CHD were adults. CONCLUSIONS: The
      prevalence in adults and median age of patients with severe CHD increased in the
      general population from 1985 to 2000. In 2000, there were nearly equal numbers of
      adults and children with severe CHD.

PMID- 17210847
TI  - The quest for genes causing complex traits in ocular medicine: successes,
      interpretations, and challenges.
AB  - Gene mapping and positional cloning have gained acceptance as state-of-the-art
      methods to identify molecules that cause common complex diseases. However, the
      use of specialized technology, varying study designs, and misconceptions about
      the role of novel findings in genetics has led to confusion among basic
      scientists and health care professionals alike regarding the importance of these
      findings in molecular diagnostics and individualized medicine. To alleviate this
      confusion, the successes achieved in the past few years in mapping of genes for
      complex traits such as age-related macular degeneration and glaucoma are
      interpreted in the context of the appropriate population biology framework. The
      current article veers away from propagating the overly simplistic belief of a
      linear relationship between a specific gene and age-related macular degeneration,
      particularly one that equates possession of a specific risk allele as the only
      precursor to end-stage disease. Ascribing predictive properties to a single gene
      without consideration of its network partners, timing of action, or environmental
      correlates argues for a static view of gene action. Modern viewpoints of the
      mechanisms of action of a gene are contextual and encompass more cohesive
      frameworks, ranging from the developmental timing of action, to the genomic and
      environmental milieu. In this regard, gene mapping studies that have been so
      immensely successful in the gene detection phase of a study provide biased
      perspectives on the importance of these genes and the corresponding risk alleles
      in the general population because of their limited sample size and constrained
      design. To move the field of gene-based diagnosis forward, it will be necessary
      to conduct additional cohort and longitudinal studies using the original gene
      finding studies as a knowledge base to develop predictive models. In summary,
      while we have achieved great successes in finding genes for complex traits, the
      application of these findings to clinical medicine is not straightforward. The
      key question of who will develop disease in the future remains.

PMID- 17210843
TI  - Myocardial ischemic memory imaging with molecular echocardiography.
AB  - BACKGROUND: Diagnosing acute coronary syndrome in patients presenting with chest
      discomfort is a challenge. Because acute myocardial ischemia/reperfusion is
      associated with endothelial upregulation of leukocyte adhesion molecules, which
      persist even after ischemia has resolved, we hypothesized that microbubbles
      designed to adhere to endothelial selectins would permit echocardiographic
      identification of recently ischemic myocardium. METHODS AND RESULTS: Lipid
      microbubbles (diameter, 3.3+/-1.7 microm) were synthesized. The selectin ligand
      sialyl Lewis(x) was conjugated to the microbubble surface (MB(sLex)). Control
      bubbles (MB(CTL)) bore surface Lewis(x) or sialyl Lewis(c). Intravital microscopy
      of mouse cremaster muscle was performed after intravenous injection of MB(sLex)
      (n=11) or MB(CTL) (n=9) with or without prior intrascrotal tumor necrosis factor
      alpha. There was greater adhesion of MB(sLex) to inflamed versus noninflamed
      endothelium (P = 0.0081). Rats (n=12) underwent 15 minutes of anterior descending
      coronary artery occlusion. After 30 minutes and 1 hour of reperfusion, high
      mechanical-index nonlinear echocardiographic imaging was performed in which
      single frames were acquired at 3.5 and 4 minutes after intravenous injection of
      MB(sLex) or MB(CTL). Video intensity at 4 minutes was subtracted from that at 3.5
      minutes to derive target-specific acoustic signal. MB(sLex) caused greater
      opacification in postischemic versus nonischemic myocardium at both time points
      (P < or = 0.002). Immunostaining confirmed endothelial P-selectin expression in
      the ischemic bed. CONCLUSIONS: Echocardiographic identification of recently
      ischemic myocardium is possible using ultrasound contrast agents targeted to
      selectins. This may offer a new approach to the more timely and precise diagnosis
      of acute coronary syndrome in patients presenting with chest pain of uncertain
      cardiac origin.

PMID- 17210848
TI  - A clinician's view of the molecular genetics of age-related maculopathy.
AB  - Molecular genetic studies of age-related maculopathy (ARM), including family
      based linkage studies and case-control association studies, have yielded valuable
      insights into the risks of developing this condition and potential disease
      causing mechanisms. Variants in the complement factor H gene and LOC387715 have
      consistently been shown to be major risk factors for ARM. Additional genes, and
      environmental, behavioral, and dietary factors, also play a major role in ARM
      pathogenesis. The present studies are a starting point toward our understanding
      of the causes of ARM and for future therapeutic studies. As clinicians, we can
      already begin to use our knowledge of ARM genetics to counsel and care for our
      patients at risk.

PMID- 17210849
TI  - Genetic etiologies of glaucoma.
AB  - Glaucoma can be inherited as a mendelian autosomal-dominant or autosomal
      recessive trait, or as a complex multifactorial trait. Genetic approaches have
      helped define the underlying molecular events responsible for some mendelian
      forms of the disease and have identified the chromosome locations of genes that
      are likely to contribute to common complex forms. Future directions include the
      discovery of new glaucoma genes, determining the clinical phenotypes associated
      with specific genes and mutations, investigating environmental factors that may
      contribute to the disease, investigating gene-environment interactions and gene
      gene interactions, and developing a mutation database that can be used for
      diagnostic and prognostic testing.

PMID- 17210850
TI  - Complex trait genetics of refractive error.
AB  - Refractive errors (myopia, hyperopia, and astigmatism) are complex heterogeneous
      disorders of the human eye and are ideal for genetic investigation. Moderate to
      severe refractive errors can predispose individuals to poor visual development,
      various types of glaucoma, misshapen corneal surfaces, premature cataracts, and
      loss of retinal integrity, which can lead to detachment. Knowledge of genetic
      mechanisms involved in refractive error susceptibility may allow treatment to
      prevent progression or to further examine gene-environment interactions. Early
      genetic predisposition detection for developing severe refractive errors may be
      useful for efficient and cost-effective screening program design. This review
      explores the genetic mechanisms associated with nonsyndromic refractive error
      development known to date.

PMID- 17210851
TI  - Cigarette smoking, CFH, APOE, ELOVL4, and risk of neovascular age-related macular
      degeneration.
AB  - OBJECTIVE: To examine if the genes encoding complement factor H (CFH),
      apolipoprotein E (APOE), and elongation of very-long-chain fatty acids-like 4
      (ELOVL4) confer risk of neovascular age-related macular degeneration (AMD) in an
      independent or interactive manner when controlling for smoking exposure. METHODS:
      We studied 103 unrelated patients with neovascular AMD who each had at least 1
      sibling with normal maculae. Smoking histories were obtained. Genotyping was
      performed by analyzing amplified genomic fragments from CFH, APOE, and ELOVL4 by
      direct sequencing or by restriction endonuclease digests. Conditional logistic
      regression analysis was used to build a multifactor model. RESULTS: For CFH, only
      the CC genotype carried a statistically significant elevation of disease risk
      (odds ratio, 49.37; 95% confidence interval, 6.20-393.22; P<.001). No significant
      association was observed between neovascular AMD and APOE or ELOVL4. No
      significant interactions were found between smoking and having the CFH or APOE
      genotype nor were significant interactions found between the CFH, ELOVL4, and
      APOE genotypes. CONCLUSIONS: Smoking and having the CFH CC genotype independently
      increase risk of neovascular AMD. APOE and ELOVL4 genotypes do not seem to modify
      risk. CLINICAL RELEVANCE: Smoking 10 pack-years or more and having the CFH CC
      genotype increase one's risk of neovascular AMD 144-fold compared with smoking
      less than 10 pack-years and having the CT or TT genotype.

PMID- 17210852
TI  - A prospective study of 2 major age-related macular degeneration susceptibility
      alleles and interactions with modifiable risk factors.
AB  - OBJECTIVES: To delineate the magnitude of susceptibility to age-related macular
      degeneration (AMD) due to common variants in the gene for complement factor H
      (CFH) and the predicted gene LOC387715 and to determine whether these variants
      interact with modifiable risk factors. METHODS: We compared cases who developed
      AMD (n = 457) with 1071 age- and sex-matched control subjects in a prospective
      nested case-control study within the Nurses' Health Study and the Health
      Professionals Follow-up Study. We determined the incidence rate ratios and 95%
      confidence intervals (CIs) for AMD for each genotype and examined the
      interactions with modifiable risk factors. RESULTS: Participants with 1 or 2
      copies of the Y402H variant of CFH were, respectively, 1.98 (95% CI, 1.64-2.40)
      and 3.92 (95% CI, 2.69-5.76) times more likely to develop AMD, whereas the
      incident rate ratios (95% CIs) for 1 and 2 copies of LOC387715 A69S were 2.38
      (1.92-2.96) and 5.66 (3.69-8.76), respectively. The fraction of AMD cases
      attributable to these 2 variants was 63% (95% CI, 58%-68%). Subjects homozygous
      for both risk alleles had a 50-fold increased risk of AMD (95% CI, 10.8-237), and
      cigarette smoking and obesity multiplied the risks associated with these
      variants. CONCLUSION: Age-related macular degeneration has emerged as a
      paradigmatic example of a common disease caused by the interplay of genetic
      predisposition and exposure to modifiable risk factors.

PMID- 17210853
TI  - Neovascular age-related macular degeneration and its association with LOC387715
      and complement factor H polymorphism.
AB  - OBJECTIVE: To compare phenotypes of 2 age-related macular degeneration (AMD)
      susceptibility genes: LOC387715 and complement factor H (CFH). METHODS:
      Phenotypes of 755 AMD cases were characterized. The number of LOC387715 (T allele
      at rs10490924, or A69S) and CFH (T1277C at rs1061170, or Y402H) risk alleles were
      determined in each case. Individuals were divided into 5 groups by genotype:
      group 1, LOC-/- CFH-/-; group 2, LOC+/- CFH-/- or LOC+/+ CFH-/-; group 3, LOC-/-
      CFH+/- or LOC-/- CFH+/+; group 4, LOC+/- CFH+/-, LOC+/+ CFH+/-, or LOC+/- CFH+/+;
      and group 5, LOC+/+ CFH+/+. RESULTS: Signs of neovascular AMD including grade (P
      = .002), pigment epithelial detachment (P = .001), and subretinal hemorrhage
      (P<.001) demonstrated significant association with groups 2, 4, and 5 vs groups 1
      and 3. Group 5 had a significantly younger mean age (72.3 years) compared with
      other groups (P = .002). CONCLUSIONS: The AMD cases possessing the LOC387715
      (rs10490924) variant may have a higher risk of neovascular AMD. Individuals with
      AMD who are homozygous for both variants might be at greater risk for earlier
      onset of neovascular AMD.

PMID- 17210854
TI  - Apolipoprotein e gene and age-related maculopathy in older individuals: the
      cardiovascular health study.
AB  - OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene
      and age-related maculopathy (ARM) in an older population. METHODS: Two thousand
      one hundred seventy persons 65 years and older sampled from 4 US communities had
      ARM signs assessed from retinal photographs using a modified Wisconsin Age
      Related Maculopathy Grading System. DNA extracted from blood samples was analyzed
      for common APOE alleles. RESULTS: After controlling for age, sex, cigarette
      smoking, and other factors, white participants carrying the epsilon2 allele had
      an increased risk of late ARM (odds ratio, 2.53 [95% confidence interval, 1.08
      5.90]) while carriers of the epsilon4 allele had a lower risk of late ARM (odds
      ratio, 0.69 [95% confidence interval, 0.19-2.50]). There were too few late ARM
      cases in African American individuals for analysis. CONCLUSION: APOE polymorphism
      is associated with late ARM in older white persons 65 years and older. Consistent
      with previous studies, the APOE epsilon2 allele is associated with a significant
      increased risk of late ARM development, whereas the epsilon4 allele may confer
      some protection.

PMID- 17210855
TI  - Identification of novel genetic loci for intraocular pressure: a genomewide scan
      of the Beaver Dam Eye Study.
AB  - OBJECTIVE: To identify genetic loci that control intraocular pressure (IOP).
      METHODS: We performed a genomewide scan of IOP, using 486 pedigrees ascertained
      through a population-based cohort, the Beaver Dam Eye Study. Linkage analysis was
      performed using the modified Haseman-Elston regression models and variance
      components linkage analysis. RESULTS: Seven regions of interest were identified
      on chromosomes 2, 5, 6, 7, 12, 15, and 19. The novel linkage region on chromosome
      19p had an empirical multipoint P value of 6.1 x 10(-5). Two of the regions (2
      and 19) were especially interesting since each has been identified as a potential
      linkage region for blood pressure. CONCLUSIONS: The results of this genomewide
      scan provide evidence that a quantitative trait locus may influence elevated IOP
      and may colocalize with blood pressure loci. These loci may control systemic
      pressure reflected in the eye and vascular system. CLINICAL RELEVANCE: Glaucoma
      is a leading cause of blindness in the world, and the identification of genes
      that contribute to this disease is essential. Elevated IOP is a principal risk
      factor for primary open-angle glaucoma and an intriguing quantitative trait that
      may strongly influence the development of disease.

PMID- 17210856
TI  - Confirmation of linkage to ocular refraction on chromosome 22q and identification
      of a novel linkage region on 1q.
AB  - OBJECTIVE: To localize genes influencing ocular refraction in subjects in the
      Beaver Dam Eye Study. Previous studies establish that myopia clusters within
      families and linkage to myopia has been demonstrated on 2q, 4q, 12q, 17q, 18q,
      22q, and Xq. Few studies have examined genetic effects across the entire range of
      refraction, though linkages to 1p, 3q, 4q, 8p, and 11p have been reported, and
      our previous analysis of the Beaver Dam Eye Study demonstrated substantial
      heritability for refraction (68%). METHODS: We conducted nonparametric sibling
      pair and genome-wide linkage analyses on spherical equivalent adjusting for age,
      education, and nuclear sclerosis, in 834 sibling pairs in 486 extended pedigrees.
      RESULTS: We identified a novel region of suggestive linkage on 1q (multipoint,
      P<.00019) and replicated the 22q region (multipoint, P = .0033) previously linked
      to myopia. Additionally, there was some evidence of linkage to 7p (multipoint, P
      = .0023). CONCLUSION: Refraction is a complex trait influenced by both genes and
      environment. Our work confirms a previously reported linkage region on 22q and
      identifies 2 novel regions of linkage on 1q and 7p. CLINICAL RELEVANCE: Further,
      genetic research is needed to finemap this trait to identify the causative gene.
      Modifying the actions of such a gene might lead to a reduction in the risk of
      refractive error.

PMID- 17210857
TI  - A new locus (GLC1H) for adult-onset primary open-angle glaucoma maps to the 2p15
      p16 region.
AB  - OBJECTIVE: To map new genetic loci for adult-onset primary open-angle glaucoma
      (POAG) by using families previously unlinked to GLC1A-GLC1F. METHODS: Initial
      genome scan and subsequent saturation mapping confirmed linkage to a locus on
      chromosome 2p15-p16. Forty-nine DNA samples from a single family with POAG with
      113 individuals were used in this study. The 10 affected members of this family
      had an average age at onset of 64 years, moderate to high intraocular pressure,
      glaucomatous visual field loss, and cup-disc ratios of 0.6 to 0.9. RESULTS:
      Haplotype construction in 9 available affected subjects established a single
      inherited chromosome from D2S123 to D2S2165, within an 11-megabase (Mb) region.
      Further analysis revealed no recombination with 8 consecutive DNA markers
      (D2S1364-D2S2332) and provided a maximum logarithm of the odds (LOD) score of
      2.97 for D2S370. Six additional families also showed consistent linkage and 1
      affected recombination may further confine this locus to an 8.3-Mb region
      (D2S2352-D2S2165). Combined analysis of 7 families provided a maximum LOD score
      of 9.30 with D2S2320. CONCLUSIONS: A new genetic locus (GLC1H) for adult-onset
      POAG maps to the 2p15-p16 region. CLINICAL RELEVANCE: Mapping of the GLC1H locus
      and eventual identification of its defective gene will help to develop diagnostic
      tools and effective treatments for this condition.

PMID- 17210858
TI  - Complement factor H polymorphism p.Tyr402His and cuticular Drusen.
AB  - OBJECTIVE: To determine the histidine frequency in patients with the cuticular
      drusen phenotype of age-related macular degeneration (AMD). METHODS: Fifty
      individuals were identified who met the criteria for the cuticular drusen
      phenotype using a standard threshold photograph. We genotyped DNA samples using a
      polymerase chain reaction-based restriction digest assay. Seven hundred
      individuals with typical AMD and 252 controls were also genotyped. Fisher exact
      test was used to analyze the significance of allele frequency differences.
      RESULTS: The histidine variant was present in 70% (frequency +/- SE, 0.70 +/-
      0.05) of the cuticular cohort, 55% (frequency +/- SE, 0.55 +/- 0.01) of the more
      typical AMD cases, and 34% (frequency +/- SE, 0.34 +/- 0.02) of controls. The
      association between the cuticular drusen phenotype and the histidine allele was
      highly significant (P = .003; odds ratio, 2.0; 95% confidence interval, 1.21
      3.07; vs AMD cases P<.001; odds ratio 4.54; 95% confidence interval, 2.79-7.50;
      vs controls). Genotype distribution between the 3 groups was similarly
      significant (P<.001). CONCLUSION: The cuticular drusen phenotype is highly
      associated with the Tyr402His variant of the complement factor H (CFH) gene. The
      significantly higher histidine allele frequency in this group compared with the
      typical AMD cohort suggests that the complement cascade may play a greater role
      in the pathogenesis of the cuticular drusen subtype than in AMD as a whole.
      CLINICAL RELEVANCE: The c.1204T>C, p.Tyr402His allelic variant in the CFH gene is
      associated with a 3-fold increased risk for AMD. A high frequency of the
      histidine allele has also been noted in patients with membranoproliferative
      glomerulonephritis type II.

PMID- 17210859
TI  - Myocilin Gly252Arg mutation and glaucoma of intermediate severity in Caucasian
      individuals.
AB  - OBJECTIVE: To determine the phenotype of an Australian pedigree with the myocilin
      (MYOC) Gly252Arg mutation, comparing it with other pedigrees carrying the same
      mutation. METHODS: All recruited subjects underwent a comprehensive clinical
      examination, including optic disc assessment, applanation tonometry, and visual
      field measurement. Mutation analysis was performed through direct sequencing.
      Haplotype analysis was performed using microsatellite markers around the MYOC
      gene. RESULTS: Eight Gly252Arg mutation carriers with glaucoma were identified
      from the same pedigree. Carriers' mean +/- SD age at diagnosis was 46.3 +/- 11.4
      years (range, 31-60 years). Highest recorded intraocular pressure ranged from 27
      to 42 mm Hg (mean +/- SD, 32.4 +/- 5.6 mm Hg). Cup-disc ratios in the worst eye
      ranged from 0.6 to 0.9. Six of the 8 individuals had undergone filtration
      surgery. A common founding haplotype between MY5 and D1S218 was found for
      Caucasian individuals tested with this mutation. One subject was compound
      heterozygotic for the MYOC Gly252Arg mutation and a novel MYOC Gly244Val variant.
      CONCLUSIONS: Although a common founder for Gly252Arg across Caucasian subjects
      was found, the phenotype from this Australian MYOC mutation-carrying pedigree is
      less severe than previously described. The severity of glaucoma caused by the
      Gly252Arg mutation may be similar to the Thr377Met MYOC mutation, yet is more
      severe than the most common Gln368Stop mutation. CLINICAL RELEVANCE: Since its
      implication in glaucoma, much work has been performed investigating the clinical
      features of MYOC-related glaucoma. Given the strong genotype-phenotype
      correlations with MYOC disease-causing variants, health care professionals armed
      with such molecular information are able to accurately counsel patients on their
      likely disease course. Our work suggests that the disease associated with MYOC
      Gly252Arg is less severe than previously described in other pedigrees with this
      specific mutation.

PMID- 17210860
TI  - Evaluation of the beta2-adrenergic receptor gene as a candidate glaucoma gene in
      2 ancestral populations.
AB  - OBJECTIVE: To determine whether the beta(2)-adrenergic receptor (ADRB2) gene is a
      glaucoma susceptibility locus. DESIGN AND METHODS: The design was an association
      study stratified by ancestry (white vs black African) and disease (primary open
      angle glaucoma vs control subjects). The ADRB2 single nucleotide polymorphisms
      were determined by sequencing, and the haplotypes of the common single nucleotide
      polymorphisms affecting codons 16 and 27 were phased by allele-specific
      polymerase chain reaction and restriction enzyme digestion. We analyzed the
      association of single nucleotide polymorphisms and haplotypes by ancestry and
      disease with the Fisher exact test, chi(2) test, and standardized Pearson
      residual. RESULTS: A total of 583 subjects underwent genotyping (156 white
      subjects with primary open-angle glaucoma; 143 subjects of black African ancestry
      with primary open-angle glaucoma; 148 white controls; and 136 controls of black
      African ancestry). There were no differences in ADRB2 alleles and haplotypes
      between the primary open-angle glaucoma and control groups, whether analyzed
      together or by ancestry. Previously described ancestry-based differences in
      allele frequencies were found. We also found ancestry-based differences in ADRB2
      haplotypes. CONCLUSION: The ADRB2 gene was not a glaucoma susceptibility locus in
      our study population. CLINICAL RELEVANCE: Because this gene is not a disease
      locus, we can now study the role of ADRB2 haplotypes in the glaucoma risk factor
      of intraocular pressure fluctuation and variation in intraocular pressure
      response to beta-blockers.

PMID- 17210861
TI  - Screening for glaucomatous disc changes prior to diagnosis of glaucoma in
      myocilin pedigrees.
AB  - OBJECTIVE: To investigate whether structural differences of the optic nerve head
      are evident in young people who do not have manifest glaucoma but are known to
      carry myocilin mutations. METHODS: A case-control design was adopted. Subjects
      from Australian pedigrees known to have either the Gln368STOP myocilin mutation
      (cutoff age, <40 years) or the Thr377Met myocilin mutation (cutoff age, <30
      years) were examined for signs of glaucoma. Stereoscopic disc photographs were
      digitalized. Analysis of the optic disc area, optic cup area, and neuroretinal
      rim area was performed using digital stereoscopy with a Z-screen. Mutation
      analysis was conducted using direct sequencing. The t test, corrected for
      multiple comparison testing, was used in analysis. RESULTS: A total of 29
      myocilin mutation-carrying (case) and 33 mutation-free (control) individuals were
      reviewed. The mean +/- SD ages were 19.9 +/- 9.0 and 22.1 +/- 9.5 years in the
      mutation and mutation-free groups, respectively (P = .35). There was no
      significant difference in intraocular pressure between mutation carriers and
      noncarriers (P = .44). There were no statistically significant differences in the
      mean disc, neuroretinal rim, and cup areas between the groups. The mean +/- SD
      neuroretinal rim area was 1.24 +/- 0.24 mm(2) in the noncarrier group and 1.25 +/
      0.23 mm(2) in the mutation group (P = .46). No notch, nerve fiber layer defect,
      or neuroretinal rim hemorrhage was noted in any eye examined. CONCLUSIONS:
      Although confounded by penetrance and expressivity, no quantified structural
      difference in the optic nerve head was observed in individuals who had a myocilin
      mutation prior to the diagnosis of glaucoma.

PMID- 17210862
TI  - Differential expression profile prioritization of positional candidate glaucoma
      genes: the GLC1C locus.
AB  - OBJECTIVES: To develop and apply a model for prioritization of candidate glaucoma
      genes. METHODS: This Affymetrix GeneChip (Affymetrix, Santa Clara, Calif) study
      of gene expression in primary culture human trabecular meshwork cells uses a
      positional differential expression profile model for prioritization of candidate
      genes within the GLC1C genetic inclusion interval. RESULTS: Sixteen genes were
      expressed under all conditions within the GLC1C interval. TMEM22 was the only
      gene within the interval with differential expression in the same direction under
      both conditions tested. Two genes, ATP1B3 and COPB2, are of interest in the
      context of a protein-misfolding model for candidate selection. SLC25A36, PCCB,
      and FNDC6 are of lesser interest because of moderate expression and changes in
      expression. Transcription factor ZBTB38 emerges as an interesting candidate gene
      because of the overall expression level, differential expression, and function.
      CONCLUSIONS: Only 1 gene in the GLC1C interval fits our model for differential
      expression under multiple glaucoma risk conditions. The use of multiple
      prioritization models resulted in filtering 7 candidate genes of higher interest
      out of the 41 known genes in the region. CLINICAL RELEVANCE: This study
      identified a small subset of genes that are most likely to harbor mutations that
      cause glaucoma linked to GLC1C.

PMID- 17210863
TI  - Analyses of a novel L130F missense mutation in FOXC1.
AB  - OBJECTIVE: To understand how the novel L130F mutation, found in 2 patients with
      Axenfeld-Rieger syndrome, disrupts function of the forkhead box C1 protein
      (FOXC1). METHODS: Sequencing DNA from patients with Axenfeld-Rieger syndrome
      identified a novel missense mutation that results in an L130F substitution in the
      FOXC1 gene. Site-directed mutagenesis was used to introduce the L130F mutation
      into the FOXC1 complementary DNA. The level of L130F protein expression was
      determined by means of immunoblotting. We determined the mutant protein's ability
      to localize to the nucleus, bind DNA, and transactivate a reporter construct.
      RESULTS: The FOXC1 L130F mutant protein is expressed at levels similar to those
      of wild-type FOXC1. The L130F protein, however, migrated at an apparent reduced
      molecular weight compared with the wild-type protein, suggesting that the mutant
      and wild-type proteins may be differentially phosphorylated. The L130F protein
      also had a significantly impaired capacity to localize to the nucleus, bind DNA,
      and transactivate reporter genes. CONCLUSIONS: The disease-causing L130F mutation
      further demonstrates that helix 3 of the forkhead domain is important for the
      FOXC1 protein to properly localize to the nucleus, bind DNA, and activate gene
      expression. CLINICAL RELEVANCE: The inability of FOXC1 to function owing to the
      L130F mutation provides further insight into how disruptions in the FOXC1 gene
      lead to human Axenfeld-Rieger syndrome.

PMID- 17210864
TI  - Phenotypic variability of pigment dispersion syndrome in children.

PMID- 17210865
TI  - BCL-6 and rituximab in diffuse large B-cell lymphoma: where are we?

PMID- 17210867
TI  - Hepatitis C virus and alanine aminotransferase kinetics following B-lymphocyte
      depletion with rituximab: evidence for a significant role of humoral immunity in
      the control of viremia in chronic HCV liver disease.

PMID- 17210869
TI  - Are Erk, Btk, and PECAM-1 major players in GPIb signaling? The challenge of
      unraveling signaling events downstream of platelet GPIb.

PMID- 17210872
TI  - Studies comparing quality of care by specialty: valid, relevant, or neither?

PMID- 17210873
TI  - A comparison of outcomes resulting from generalist vs specialist care for a
      single discrete medical condition: a systematic review and methodologic critique.
AB  - BACKGROUND: Studies of clinical outcomes for generalist vs specialist care for
      diagnoses within a specialist's narrow domain have tended to favor specialty
      care. METHODS: A MEDLINE search from January 1, 1980, through April 1, 2005, and
      a hand search of retrieved bibliographies of English-language studies that
      compared generalist vs specialist care for individual patients with a single
      discrete medical condition were performed. Two reviewers determined eligibility
      for each study and abstracted data onto a standardized instrument. RESULTS: A
      total of 49 articles met our inclusion criteria: 24 studies favored specialty
      care, 13 found no difference in outcomes, 7 varied by individual outcome, 1
      depended on physician experience, and 4 favored generalist care. Only 8 studies
      reported integration into health delivery systems, 4 considered physician
      experience, 3 documented information technology support, and 2 considered the
      impact of care management programs. Selection bias was adequately addressed in
      58% of studies that favored specialty care and in 71% of studies that found no
      difference or favored generalist care (P = .52). Studies that favored specialty
      care were less likely to consider 4 key, potentially confounding physician or
      practice characteristics compared with studies that found no difference or
      favored generalist care (3% vs 15% of potential instances, respectively; P =
      .009). CONCLUSIONS: The literature regarding the influence of generalist vs
      specialist care on outcomes for patients with a single discrete condition suffers
      from important methodologic shortcomings. Further research is needed to inform
      health care policy as it pertains to the optimal role of generalists and
      specialists in the physician marketplace.

PMID- 17210874
TI  - Vitamin B6, B12, and folic acid supplementation and cognitive function: a
      systematic review of randomized trials.
AB  - BACKGROUND: Despite their important role in cognitive function, the value of B
      vitamin supplementation is unknown. A systematic review of the effect of
      pyridoxine hydrochloride (hereinafter "vitamin B(6)"), cyanocobalamin or
      hydroxycobalamin (hereinafter "vitamin B(12)"), and folic acid supplementation on
      cognitive function was performed. METHODS: Literature search conducted in MEDLINE
      with supplemental articles from reviews and domain experts. We included English
      language randomized controlled trials of vitamins B(6) and/or B(12) and/or folic
      acid supplementation with cognitive function outcomes. RESULTS: Fourteen trials
      met our criteria; most were of low quality and limited applicability.
      Approximately 50 different cognitive function tests were assessed. Three trials
      of vitamin B(6) and 6 of vitamin B(12) found no effect overall in a variety of
      doses, routes of administration, and populations. One of 3 trials of folic acid
      found a benefit in cognitive function in people with cognitive impairment and low
      baseline serum folate levels. Six trials of combinations of the B vitamins all
      concluded that the interventions had no effect on cognitive function. Among 3
      trials, those in the placebo arm had greater improvements in a small number of
      cognitive tests than participants receiving either folic acid or combination B
      vitamin supplements. The evidence was limited by a sparsity of studies, small
      sample size, heterogeneity in outcomes, and a lack of studies that evaluated
      symptoms or clinical outcomes. CONCLUSION: The evidence does not yet provide
      adequate evidence of an effect of vitamin B(6) or B(12) or folic acid
      supplementation, alone or in combination, on cognitive function testing in people
      with either normal or impaired cognitive function.

PMID- 17210875
TI  - The effect of weight loss on C-reactive protein: a systematic review.
AB  - BACKGROUND: Several studies suggest that weight loss reduces C-reactive protein
      (CRP) level; however, the consistency and magnitude of this effect has not been
      well characterized. Our objective was to test the hypothesis that weight loss is
      directly related to a decline in CRP level. DATA SOURCES: We searched the
      Cochrane Controlled Trials Register and MEDLINE databases and conducted hand
      searches and reviews of bibliographies to identify relevant weight loss
      intervention studies. STUDY SELECTION: We included all weight loss intervention
      studies that had at least 1 arm that was a surgical, lifestyle, dietary, and/or
      exercise intervention. Abstracts were independently selected by 2 reviewers. DATA
      EXTRACTION: Two reviewers independently abstracted data on the characteristics of
      each study population, weight loss intervention, and change in weight and CRP
      level from each arm of all included studies. DATA SYNTHESIS: We analyzed the mean
      change in CRP level (milligrams per liter) and the mean weight change
      (kilograms), comparing the preintervention and postintervention values from each
      arm of 33 included studies using graphical displays of these data and weighted
      regression analyses to quantify the association. RESULTS: Weight loss was
      associated with a decline in CRP level. Across all studies (lifestyle and
      surgical interventions), we found that for each 1 kg of weight loss, the mean
      change in CRP level was -0.13 mg/L (weighted Pearson correlation, r = 0.85). The
      weighted correlation for weight and change in CRP level in the lifestyle
      interventions alone was 0.30 (slope, 0.06). The association appeared roughly
      linear. CONCLUSION: Our results suggest that weight loss may be an effective
      nonpharmacologic strategy for lowering CRP level.

PMID- 17210876
TI  - End-of-life care: findings from a national survey of informal caregivers.
AB  - BACKGROUND: Family and friends are thought to be the predominant providers of end
      of-life care, although nationally representative data on this topic have been
      lacking. METHODS: This study draws from the 1999 National Long-Term Care Survey
      and its Informal Caregivers Survey to characterize primary informal caregivers'
      experiences providing end-of-life care to chronically disabled community-dwelling
      older adults. Study participants were 1149 primary informal caregivers,
      stratified by care recipients' survival or death during the following 12 months.
      RESULTS: An estimated 11.2% of the chronically disabled community-dwelling older
      adults died within 1 year of being interviewed. Among persons who died, 72.3%
      were receiving help from an informal caregiver at the time of the interview. End
      of-life primary informal caregivers helped an average of 43 hours per week, 84.4%
      provided daily assistance, and caregiver support services were infrequently used
      (ie, respite care and support groups were used by less than 5% of caregivers).
      While end-of-life caregivers reported significant emotional (28.9%), physical
      (18.4%), and financial (14.0%) strains, more than two thirds endorsed personal
      rewards related to their helping role. Compared with primary informal caregivers
      of persons who survived the following 12 months, end-of-life caregivers provided
      significantly higher levels of assistance and reported more challenges and
      strains, but they were no less likely to endorse rewards related to their helping
      role. CONCLUSIONS: End-of-life caregivers provide frequent and intense assistance
      with few supportive services. These data underscore the relevance of families to
      end-of-life care, and the potential benefit of better integrating families in
      patient care.

PMID- 17210877
TI  - House staff team workload and organization effects on patient outcomes in an
      academic general internal medicine inpatient service.
AB  - BACKGROUND: House staff work-hour regulations have required residency programs to
      reengineer inpatient services. However, few data describe how house staff
      workload on a patient's day of admission or on subsequent hospital days
      influences patient outcomes. METHODS: Retrospective cohort analysis of 5742
      adults admitted to an academic general medical service between July 1, 1998, and
      June 30, 2001. RESULTS: After multivariate risk adjustment for patient severity
      and other structural factors, we found that 2 different measures of house staff
      workload significantly affected patient outcomes. House staff workload increases
      on the day of admission, defined as each additional team admission on a patient's
      admission day, increased length of stay (difference, 3.09%; 95% confidence
      interval [CI], 2.22%-3.96%), total costs (difference, 2.31%; 95% CI, 1.29%
      3.33%), and risk of inpatient mortality (odds ratio, 1.09; 95% CI, 1.02-1.15).
      Patients had an even higher mortality risk when more than 9 patients were
      admitted to their team on their admission day. In contrast, house staff workload
      increases during the patient's entire stay, defined as every additional patient
      added to the team average census, reduced length of stay (difference, -5.30%; 95%
      CI, -4.54% to -6.07%) and total costs (difference, -5.11%; 95% CI, -4.20% to 
      6.00%). Reductions in length of stay and costs were most striking when the team
      average census exceeded 15 patients. CONCLUSIONS: Our findings suggest that
      higher house staff workload on admitting days-when fewer backup resources are
      available-increases resource use and may increase inpatient mortality.
      Conversely, a higher average team census was associated with reduced resource
      use, perhaps reflecting service-level adaptations to workload. Future studies
      should confirm these findings in larger trials.

PMID- 17210878
TI  - Influenza vaccination and risk of mortality among adults hospitalized with
      community-acquired pneumonia.
AB  - BACKGROUND: Influenza vaccination has been shown to reduce illness and all-cause
      mortality in vulnerable populations through the prevention of influenza
      infection. Attenuation of the severity of illness by vaccination has been
      reported for respiratory tract infections due to bacterial pathogens and would
      represent an important additional health benefit of influenza vaccination. We
      evaluated the impact of prior influenza vaccination on in-hospital mortality and
      other health outcomes among hospitalized adults with community-acquired pneumonia
      (CAP). METHODS: Consecutive individuals hospitalized with CAP during "influenza
      season" (November to April, 1999-2003) at hospitals operated by Tenet HealthCare
      were identified using a database constructed to improve quality of patient care.
      Associations between vaccination status and all-cause in-hospital mortality were
      evaluated using logistic regression models. RESULTS: Among 17 393 adults
      hospitalized with CAP during the study period, 1590 (19% of those with recorded
      vaccine status) had a history of influenza vaccination in the current or most
      recent influenza season. Vaccine recipients were less likely to die in hospital
      of any cause than individuals without vaccination (odds ratio, 0.30; 95%
      confidence interval, 0.22-0.41). These effects remained significant after
      adjustment for the presence of comorbid illnesses and pneumococcal vaccination
      (adjusted odds ratio for death, 0.61; 95% confidence interval, 0.43-0.87) and
      under widely varying assumptions about individuals with missing vaccination
      status. CONCLUSIONS: Prior influenza vaccination was associated with improved
      survival in hospitalized patients with CAP during influenza season. This
      observation, if confirmed by other studies, would represent an important
      additional benefit of enhanced influenza vaccine coverage.

PMID- 17210879
TI  - Depressive symptoms and chronic obstructive pulmonary disease: effect on
      mortality, hospital readmission, symptom burden, functional status, and quality
      of life.
AB  - BACKGROUND: Depressive symptoms are common among patients with chronic
      obstructive pulmonary disease (COPD), but depression's impact on COPD outcomes
      has not been fully investigated. We evaluated the impact of comorbid depression
      on mortality, hospital readmission, smoking behavior, respiratory symptom burden,
      and physical and social functioning in patients with COPD. METHODS: In this
      prospective cohort study, 376 consecutive patients with COPD hospitalized for
      acute exacerbation were followed up for 1 year. The independent associations of
      baseline comorbid depression (designated as a Hospital Anxiety and Depression
      Scale score of > or =8) with mortality, hospital readmission, length of stay,
      persistent smoking, and quality of life (determined by responses to the St George
      Respiratory Questionnaire) were evaluated after adjusting for potential
      confounders. RESULTS: The prevalence of depression at admission was 44.4%. The
      median follow-up duration was 369 days, during which 57 patients (15.2%) died,
      and 202 (53.7%) were readmitted at least once. Multivariate analyses showed that
      depression was significantly associated with mortality (hazard ratio, 1.93; 95%
      confidence interval, 1.04-3.58), longer index stay (mean, 1.1 more days; P = .02)
      and total stay (mean, 3.0 more days; P = .047), persistent smoking at 6 months
      (odds ratio, 2.30; 95% confidence interval, 1.17-4.52), and 12% to 37% worse
      symptoms, activities, and impact subscale scores and total score on the St George
      Respiratory Questionnaire at the index hospitalization and 1 year later, even
      after controlling for chronicity and severity of COPD, comorbidities, and
      behavioral, psychosocial, and socioeconomic variables. CONCLUSIONS: Comorbid
      depressive symptoms in patients with COPD are associated with poorer survival,
      longer hospitalization stay, persistent smoking, increased symptom burden, and
      poorer physical and social functioning. Interventions that reduce depressive
      symptoms may potentially affect COPD outcomes.

PMID- 17210880
TI  - External validity of clinical trials in acute myocardial infarction.
AB  - BACKGROUND: Patients enrolled in randomized clinical trials (RCTs) may not
      reflect those seen in real-life practice. Our goal was to compare patients
      eligible for enrollment but not enrolled in contemporary RCTs of reperfusion
      therapy with patients who would have been ineligible and also with patients with
      acute myocardial infarction (AMI) participating in RCTs. METHODS: Consecutive
      patients with AMI (n = 8469) enrolled in the GRACE registry (Global Registry of
      Acute Coronary Events) were divided into 3 groups: RCT participants (11%; n =
      953), eligible nonenrolled patients (55%; n = 4669), and ineligible patients
      (34%; n = 2847). Our main outcome measures were hospital mortality rates.
      RESULTS: Based on baseline characteristics or GRACE risk-score distribution, RCT
      participants had the lowest a priori risk of death; eligible patients had a
      higher risk; and ineligible patients had the highest risk. Actual hospital
      mortality showed a similar gradient (3.6%, 7.1%, and 11.4%, respectively)
      (P<.001). Multivariable analysis adjusting for baseline risk, use and type of
      reperfusion therapy, and delay from symptom onset to admission consistently
      showed a higher mortality rate for eligible nonenrolled patients than for RCT
      participants (odds ratio, 1.61; 95% confidence interval, 1.06-2.43; and odds
      ratio, 1.97; 95% confidence interval, 1.24-3.13, respectively). CONCLUSIONS:
      Patients with AMI participating in RCTs have a lower baseline risk and experience
      lower mortality than nonenrolled patients, even when they are trial eligible.
      This difference is not entirely explained by differences in baseline risk, use
      and type of reperfusion therapy, and/or delays in presentation. Caution is
      necessary when extending the findings obtained in RCTs to the general population
      with AMI.

PMID- 17210881
TI  - Effectiveness and cost-effectiveness of thrombolysis in submassive pulmonary
      embolism.
AB  - BACKGROUND: Thrombolytic therapy is controversial in patients with submassive
      pulmonary embolism. METHODS: We performed a cost-effectiveness analysis to
      compare health effects and costs of treatment with alteplase plus heparin sodium
      vs heparin alone in hemodynamically stable patients with pulmonary embolism and
      right ventricular dysfunction by developing a Markov model and using data from
      clinical trials and administrative sources. RESULTS: Based on data from a recent
      randomized trial, we assumed that the risk of clinical deterioration requiring
      treatment escalation was almost 3 times higher in patients who received heparin
      alone (23.2% vs 7.6%) but that the risk of death was equal in the 2 cohorts
      (2.7%). Based on registry data, we assumed that the risk of intracranial
      hemorrhage was approximately 3 times higher in patients who received alteplase
      plus heparin (1.2% vs 0.4%). Under these and other assumptions, thrombolysis
      resulted in marginally higher total lifetime health care costs ($43,900 vs
      $43,300) and was slightly less effective (10.52 vs 10.57 quality-adjusted life
      years) than treatment with heparin alone. Thrombolysis was more effective and
      cost less than $50,000 per quality-adjusted life-year gained when we assumed that
      the baseline risk of death in the heparin group was 3 times the base-case value
      (8.1%) and that alteplase reduced the relative risk of death by at least 10%.
      CONCLUSIONS: Available data do not support the routine use of thrombolysis to
      treat patients with submassive pulmonary embolism. However, thrombolysis may
      prove to be cost-effective in selected subgroups of hemodynamically stable
      patients in whom the risk of death is higher.

PMID- 17210882
TI  - Risk of rapid global functional decline in elderly patients with severe cerebral
      age-related white matter changes: the LADIS study.
AB  - BACKGROUND: Age-related white matter changes (ARWMCs), frequently detected on
      neuroimaging, are associated with motor, cognitive, urinary, and mood disorders.
      The LADIS (LeukoAraiosis and DISability) Study primarily aims to assess ARWMCs as
      a determinant of global functional decline in the elderly population. METHODS: We
      enrolled 639 patients (mean age, 74.1 +/- 5.0 years; 45.1% male) referred for
      nondisabling complaints, who had ARWMCs detected on brain magnetic resonance
      imaging (MRI) of mild, moderate, or severe grade according to the Fazekas scale.
      At the 1-year follow-up, 619 were reassessed using the Instrumental Activities of
      Daily Living (IADL) scale. Of these, 506 were totally independent at baseline,
      and 113 were impaired in only 1 item of the IADL scale. We studied the 1-year
      transition to 2 or more activities limited and selective functional impairments
      as cofactors of functional decline. RESULTS: The rate of transition was 9%, 15%,
      and 26%, in the mild, moderate, and severe ARWMC group, respectively. Comparing
      the severe with the mild ARWMC groups and adjusting for age and for other
      predictors of decline, the risk was more than 2-fold higher (odds ratio; 2.38;
      95% confidence interval, 1.29-4.38) in patients with 0 or 1 activity limited, and
      3-fold higher (odds ratio, 3.02; 95% confidence interval, 1.34-6.78) among
      patients fully independent at baseline. Both motor and cognitive deterioration
      predominantly explained the effect of ARWMCs on global functional decline.
      CONCLUSION: Elderly patients who are functionally independent and who have severe
      ARWMCs are at considerable risk of becoming more dependent in a short period,
      mostly owing to motor and cognitive deterioration.

PMID- 17210883
TI  - Water as a source of health care-associated infections.

PMID- 17210884
TI  - Possible involvements of vitamin K in bone quality.

PMID- 17210885
TI  - Vitamin K and the prevention of fractures.

PMID- 17210886
TI  - Bell palsy: which side?

PMID- 17210887
TI  - Enzyme replacement for infantile Pompe disease: the first step toward a cure.

PMID- 17210888
TI  - Is decreased dexterity in Parkinson disease due to apraxia?

PMID- 17210889
TI  - Neurologic phenotypes associated with acanthocytosis.
AB  - The term "neuroacanthocytosis" is normally used to refer to autosomal recessive
      chorea-acanthocytosis and X-linked McLeod syndrome, but there are other movement
      disorders in which erythrocyte acanthocytosis may also be seen, such as
      Huntington disease-like 2 and pantothenate kinase-associated neurodegeneration.
      Disorders of serum lipoproteins such as Bassen-Kornzweig disease form a distinct
      group of neuroacanthocytosis syndromes in which ataxia is observed, but movement
      disorders are not seen. Genetic testing has enabled us to distinguish between
      these disorders, even when there are considerable similarities between
      phenotypes. Improved detection is important for accurate genetic counseling, for
      monitoring for complications, and, it is hoped, for implementing causal
      treatments, once these become available. As in other neurodegenerative
      conditions, animal models are a promising strategy for the development of such
      therapies.

PMID- 17210890
TI  - Broad spectrum of Pompe disease in patients with the same c.-32-13T->G haplotype.
AB  - BACKGROUND: Pompe disease (acid maltase deficiency, glycogen storage disease type
      II; OMIM 232300) is an autosomal recessive lysosomal storage disorder
      characterized by acid alpha-glucosidase deficiency due to mutations in the GAA
      gene. Progressive skeletal muscle weakness affects motor and respiratory
      functions and is typical for all forms of Pompe disease. Cardiac hypertrophy is
      an additional fatal symptom in the classic infantile subtype. c.-32-13T-->G is
      the most common mutation in adults. OBJECTIVE: To delineate the disease variation
      among patients with this mutation and to define the c.-32-13T-->G haplotypes in
      search for genotype-phenotype correlations. METHODS: We studied 98 compound
      heterozygotes with a fully deleterious mutation (11 novel mutations are
      described) and the common c.-32-13T-->G mutation. RESULTS: All patients were
      Caucasian. None had the classic infantile form of Pompe disease. The clinical
      course varied far more than anticipated (age at diagnosis <1 to 78 years; age at
      onset: <1 to 52 years). The acid alpha-glucosidase activities in a subset of
      patients ranged from 4 to 19.9 nmol/mg/h. Twelve different c.-32-13T-->G
      haplotypes were identified based on 17 single-nucleotide polymorphisms located in
      the GAA gene. In 76% of the cases, c.-32-13T-->G was encountered in the second
      most common GAA core haplotype (DHRGEVVT). In only one case was c.-32-13T-->G
      encountered in the major GAA core haplotype (DRHGEIVT). CONCLUSION: Patients with
      the same c.-32-13T-->G haplotype (c.q. GAA genotype) may manifest first symptoms
      at different ages, indicating that secondary factors may substantially influence
      the clinical course of patients with this mutation.

PMID- 17210891
TI  - The increasing incidence of anticoagulant-associated intracerebral hemorrhage.
AB  - OBJECTIVE: To define temporal trends in the incidence of anticoagulant-associated
      intracerebral hemorrhage (AAICH) during the 1990s and relate them to rates of
      cardioembolic ischemic stroke. METHODS: We identified all patients hospitalized
      with first-ever intracerebral hemorrhage (ICH) in greater Cincinnati during 1988,
      from July 1993 through June 1994, and during 1999. AAICH was defined as ICH in
      patients receiving warfarin or heparin. Patients from the same region
      hospitalized with first-ever ischemic stroke of cardioembolic mechanism were
      identified during 1993/1994 and 1999. Incidence rates were calculated and
      adjusted to the 2000 US population. Estimates of warfarin distribution in the
      United States were obtained for the years 1988 through 2004. RESULTS: AAICH
      occurred in 9 of 184 ICH cases (5%) in 1988, 23 of 267 cases (9%) in 1993/1994,
      and 54 of 311 cases (17%) in 1999 (p < 0.001). The annual incidence of AAICH per
      100,000 persons was 0.8 (95% CI 0.3 to 1.3) in 1988, 1.9 (1.1 to 2.7) in
      1993/1994, and 4.4 (3.2 to 5.5) in 1999 (p < 0.001 for trend). Among persons aged
      > or =80, the AAICH rate increased from 2.5 (0 to 7.4) in 1988 to 45.9 (25.6 to
      66.2) in 1999 (p < 0.001 for trend). Incidence rates of cardioembolic ischemic
      stroke were similar in 1993/1994 and 1999 (31.1 vs 30.4, p = 0.65). Warfarin
      distribution in the United States quadrupled on a per-capita basis between 1988
      and 1999. CONCLUSIONS: The incidence of anticoagulant-associated intracerebral
      hemorrhage quintupled in our population during the 1990s. The majority of this
      change can be explained by increasing warfarin use. Anticoagulant-associated
      intracerebral hemorrhage now occurs at a frequency comparable to subarachnoid
      hemorrhage.

PMID- 17210892
TI  - The value of interictal diffusion-weighted imaging in lateralizing temporal lobe
      epilepsy.
AB  - BACKGROUND: A subgroup of patients with nonlesional temporal lobe epilepsy (TLE)
      has no evidence of hippocampal sclerosis on standard temporal lobe protocol MRI.
      OBJECTIVE: To investigate whether interictal diffusion-weighted imaging adds
      lateralizing information in patients with TLE with and without lateralizing
      conventional MRI. METHODS: We studied 22 patients (9 right, 13 left TLE) who had
      undergone temporal lobectomy and 18 control subjects. We measured hippocampal
      volumes on high- resolution coronal magnetization-prepared rapid gradient echo
      scans. Apparent diffusion coefficients (ADCs) for the entire hippocampus and
      three arbitrarily defined areas of interest within the hippocampal head, body,
      and tail were measured from the coregistered ADC map. Pathology was reviewed and
      correlated with imaging findings. RESULTS: Fourteen of 22 patients had
      hippocampal atrophy on MRI (defined as volume asymmetry greater than 2 SDs
      compared with asymmetry in the control group). Overall, resected hippocampi (n =
      22) were significantly smaller than contralateral hippocampi as well as
      ipsilateral hippocampi in controls. ADCs were significantly higher in resected
      hippocampi than contralateral hippocampi as well as ipsilateral hippocampi in
      controls. These differences were also observed within the three areas of
      interest. ADCs in the hippocampi contralateral to the epileptogenic zone (n = 22)
      were also higher than in ipsilateral hippocampi in controls. In the subgroup of
      eight patients with nonlateralizing conventional MRIs, ADCs of resected
      hippocampi were not significantly different compared with the contralateral side.
      Pathology in these patients revealed gliosis only without apparent neuron loss.
      CONCLUSION: Interictal apparent diffusion coefficients confirm lateralization in
      patients with hippocampal atrophy on standard temporal lobe protocol MRI.
      However, they do not provide lateralizing information in patients with
      nonlateralizing conventional MRI.

PMID- 17210893
TI  - Prism adaptation to optical deviation alleviates pathologic pain.
AB  - BACKGROUND: The human visual and somatosensory systems are interdependent. Using
      a visual subjective body-midline (SM) judgment task, we previously confirmed that
      pathologic pain and deafferentation can modify visuospatial perception,
      indicating that altered somatosensory experience can modify visual perception.
      Conversely, in the present study we investigated whether a change in visual
      experience can modify perception of pathologic pain. METHODS: We used prism
      adaptation (PA) to modify subjects' visual experience. Five patients with complex
      regional pain syndrome (CRPS) adapted to wedge prisms, producing a 20-degree
      visual displacement toward the unaffected side. Further, we used several types of
      prisms in a longitudinal single-case study. Wearing prismatic goggles, the
      subjects performed a target-pointing task once a day for 2 weeks. We evaluated
      pain intensity and visual SM judgment to measure the adaptive aftereffects at
      three time points: before PA (pre-test), immediately after the first PA exposure
      (IA-test), and after a 14-day sequence of PA exposure (post-test). RESULTS: PA
      toward the unaffected side alleviated pathologic pain and other CRPS pathologic
      features, when measured at post-test. None of the IA-test results showed an
      analgesic effect. In the longitudinal study, sham PA and 5-degree PA did not
      produce any effects, and PA toward the affected side actually exacerbated the
      subjective pain. CONCLUSIONS: Our findings suggest that vision can influence
      pathologic pain, and preliminarily suggest that prism adaptation has a direction
      specific and reproducible effect on not only pathologic pain but also other CRPS
      pathologic features. Thus, prism adaptation may be a viable cognitive treatment
      for CRPS.

PMID- 17210894
TI  - High prevalence of somatic symptoms and depression in women with disabling
      chronic headache.
AB  - OBJECTIVE: To better define, in women with headache, the relationship of
      depression and somatic symptoms to headache, characterized by diagnoses,
      frequency, and disability. METHODS: At six headache specialty clinics, women with
      headache were classified using ICHD-II criteria, and frequency was recorded. A
      questionnaire addressing demographics, age at onset of headache, headache-related
      disability, somatic symptom, and depression severity was completed. Logistic
      regression was performed to measure the associations of headache frequency and
      headache-related disability with somatic symptom and depression severity.
      RESULTS: A total of 1,032 women with headache completed the survey, 593 with
      episodic (96% with migraine) and 439 with chronic headache (87% with migraine).
      Low education and household income was more common in chronic headache sufferers
      and in persons with severe headache disability. Somatic symptom prevalence and
      severity was greater in persons with chronic headache and with severe headache
      related disability. Significant correlation was observed between PHQ-9 and PHQ-15
      scores (r = 0.62). Chronic headache, severe disability, and high somatic symptom
      severity were associated with major depressive disorder (OR = 25.1, 95% CI: 10.9
      to 57.9), and this relationship was stronger in the subgroup with a diagnosis of
      migraine (OR = 31.8, 95% CI: 12.9 to 78.5). CONCLUSIONS: High somatic symptom
      severity is prevalent in women with chronic and severely disabling headaches.
      Synergistic relationship to major depression exists for high somatic symptom
      severity, chronic headache, and disabling headache, suggesting a psychobiological
      underpinning of these associations.

PMID- 17210895
TI  - Swiss cheese brain.

PMID- 17210896
TI  - Incidence of ALS in Lombardy, Italy.
AB  - OBJECTIVE: To assess the incidence and trends of ALS in a large population at
      risk. METHODS: This study was performed in nine provinces of Lombardy in Northern
      Italy (population 4,947,554). Patients with newly diagnosed ALS were enrolled
      during the period 1998 to 2002 through a prospective regional register. For each
      patient, the main demographic and clinical information was collected by the
      caring physicians and reviewed by a panel of experts according to the original
      and revised El Escorial diagnostic criteria. Overall, age- and sex-specific and
      standardized annual incidence rates were calculated for the entire population and
      for each year and province separately. RESULTS: We studied 517 patients (M:F
      ratio 1.3) aged 18 to 92 years (mean 63.6). Onset of symptoms was bulbar in 29%
      of cases. ALS was definite in 45%, probable in 27%, probable laboratory supported
      in 3.5%, possible in 15%, and suspected in 10%. Mean disease duration at
      diagnosis was 10.6 months. The standardized incidence rate was 2.09 per
      100,000/year (95% CI: 1.17 to 3.18). The rate, which was 2.43 in men and 1.76 in
      women, tended to increase up to ages 65 to 74 and to decrease thereafter. The
      rate was unchanged over time and presented moderate variations across provinces.
      The incidence rate of definite ALS was 0.93 (spinal-onset ALS 1.35; bulbar-onset
      ALS 0.74) and was consistently higher in men with spinal-onset ALS vs men with
      bulbar-onset ALS and women. CONCLUSIONS: The incidence of ALS varied according to
      age, sex, and site of onset. No temporal and geographic clusters were detected
      over a 5-year period.

PMID- 17210898
TI  - Pathologic pain distorts visuospatial perception.
AB  - Spatial perception is achieved by integrating multisensory information. Using
      visual subjective body midline (vSM) judgments in patients with unilateral limb
      pain (complex regional pain syndrome [CRPS]), we found that their vSM deviated
      toward the affected side; however, deafferentation of the affected limb caused a
      transient pain decrease and a transient shift of the vSM deviation toward the
      unaffected side. Our results indicate that the persistent pain state in CRPS
      distorts visuospatial perception.

PMID- 17210897
TI  - Phenylpropanolamine contained in cold remedies and risk of hemorrhagic stroke.
AB  - In this study, we sought to elucidate whether phenylpropanolamine (PPA) in cold
      remedies (small and divided doses) increases the risk of hemorrhagic stroke (HS).
      PPA exposure significantly increased the risk, and the risk was much higher in
      women. In women, linear trends were also found in recency, duration, and dosage
      of PPA exposure. PPA contained in cold remedies increases the risk of HS,
      particularly in women.

PMID- 17210899
TI  - CSF pressure assessed by lumbar puncture agrees with intracranial pressure.
AB  - The accuracy of estimating intracranial pressure in brain tissue (ICP(BT)) via
      lumbar space was investigated using preset pressure levels in the interval 0 to
      600 mm H(2)O in patients with communicating hydrocephalus. Lumbar space ICP
      correlated excellently to ICP(BT), demonstrated by a measured mean difference of
      10 mm H(2)O (0.75 mm Hg) and a regression coefficient of 0.98. The concurrence
      supports the lumbar puncture as an accurate technique to determine ICP in
      patients with communicating CSF systems.

PMID- 17210900
TI  - Paraplegia caused by invasive spinal aspergillosis.

PMID- 17210902
TI  - Deep brain pallidal stimulation for movement disorders in neuroacanthocytosis.

PMID- 17210901
TI  - GPi deep brain stimulation for Tourette syndrome improves tics and psychiatric
      comorbidities.

PMID- 17210903
TI  - Chronic autoimmune autonomic neuropathy responsive to immunosuppressive therapy.

PMID- 17210904
TI  - A 3-year clinical follow-up of adult patients with 3243A>G in mitochondrial DNA.

PMID- 17210905
TI  - Detection of intracranial venous reflux in patients of transient global amnesia.

PMID- 17210906
TI  - Practice Parameter: neuroprotective strategies and alternative therapies for
      Parkinson disease (an evidence-based review): report of the Quality Standards
      Subcommittee of the American Academy of Neurology.

PMID- 17210908
TI  - Nighttime stomatal conductance and transpiration in C3 and C4 plants.

PMID- 17210909
TI  - Heavy water fractionation during transpiration.

PMID- 17210910
TI  - The control of transpiration. Insights from Arabidopsis.

PMID- 17210911
TI  - Freshly excavated fossil bones are best for amplification of ancient DNA.
AB  - Despite the enormous potential of analyses of ancient DNA for phylogeographic
      studies of past populations, the impact these analyses, most of which are
      performed with fossil samples from natural history museum collections, has been
      limited to some extent by the inefficient recovery of ancient genetic material.
      Here we show that the standard storage conditions and/or treatments of fossil
      bones in these collections can be detrimental to DNA survival. Using a
      quantitative paleogenetic analysis of 247 herbivore fossil bones up to 50,000
      years old and originating from 60 different archeological and paleontological
      contexts, we demonstrate that freshly excavated and nontreated unwashed bones
      contain six times more DNA and yield twice as many authentic DNA sequences as
      bones treated with standard procedures. This effect was even more pronounced with
      bones from one Neolithic site, where only freshly excavated bones yielded
      results. Finally, we compared the DNA content in the fossil bones of one animal,
      a approximately 3,200-year-old aurochs, excavated in two separate seasons 57
      years apart. Whereas the washed museum-stored fossil bones did not permit any DNA
      amplification, all recently excavated bones yielded authentic aurochs sequences.
      We established that during the 57 years when the aurochs bones were stored in a
      collection, at least as much amplifiable DNA was lost as during the previous
      3,200 years of burial. This result calls for a revision of the postexcavation
      treatment of fossil bones to better preserve the genetic heritage of past life
      forms.

PMID- 17210912
TI  - Identification of a subpopulation of cells with cancer stem cell properties in
      head and neck squamous cell carcinoma.
AB  - Like many epithelial tumors, head and neck squamous cell carcinoma (HNSCC)
      contains a heterogeneous population of cancer cells. We developed an
      immunodeficient mouse model to test the tumorigenic potential of different
      populations of cancer cells derived from primary, unmanipulated human HNSCC
      samples. We show that a minority population of CD44(+) cancer cells, which
      typically comprise <10% of the cells in a HNSCC tumor, but not the CD44(-) cancer
      cells, gave rise to new tumors in vivo. Immunohistochemistry revealed that the
      CD44(+) cancer cells have a primitive cellular morphology and costain with the
      basal cell marker Cytokeratin 5/14, whereas the CD44(-) cancer cells resemble
      differentiated squamous epithelium and express the differentiation marker
      Involucrin. The tumors that arose from purified CD44(+) cells reproduced the
      original tumor heterogeneity and could be serially passaged, thus demonstrating
      the two defining properties of stem cells: ability to self-renew and to
      differentiate. Furthermore, the tumorigenic CD44(+) cells differentially express
      the BMI1 gene, at both the RNA and protein levels. By immunohistochemical
      analysis, the CD44(+) cells in the tumor express high levels of nuclear BMI1, and
      are arrayed in characteristic tumor microdomains. BMI1 has been demonstrated to
      play a role in self-renewal in other stem cell types and to be involved in
      tumorigenesis. Taken together, these data demonstrate that cells within the
      CD44(+) population of human HNSCC possess the unique properties of cancer stem
      cells in functional assays for cancer stem cell self-renewal and differentiation
      and form unique histological microdomains that may aid in cancer diagnosis.

PMID- 17210914
TI  - Role for rearranged variable gene segments in directing secondary T cell receptor
      alpha recombination.
AB  - During the recombination of variable (V) and joining (J) gene segments at the T
      cell receptor alpha locus, a ValphaJalpha joint resulting from primary
      rearrangement can be replaced by subsequent rounds of secondary rearrangement
      that use progressively more 5' Valpha segments and progressively more 3' Jalpha
      segments. To understand the mechanisms that target secondary T cell receptor
      alpha recombination, we studied the behavior of a T cell receptor alpha allele
      (HYalpha) engineered to mimic a natural primary rearrangement of TRAV17 to
      Jalpha57. The introduced ValphaJalpha segment was shown to provide chromatin
      accessibility to Jalpha segments situated within several kilobases downstream and
      to suppress germ-line Jalpha promoter activity and accessibility at greater
      distances. As a consequence, the ValphaJalpha segment directed secondary
      recombination events to a subset of Jalpha segments immediately downstream from
      the primary rearrangement. The data provide the mechanistic basis for a model of
      primary and secondary T cell receptor alpha recombination in which recombination
      events progress in multiple small steps down the Jalpha array.

PMID- 17210913
TI  - The crystal structure of the rhomboid peptidase from Haemophilus influenzae
      provides insight into intramembrane proteolysis.
AB  - Rhomboid peptidases are members of a family of regulated intramembrane peptidases
      that cleave the transmembrane segments of integral membrane proteins. Rhomboid
      peptidases have been shown to play a major role in developmental processes in
      Drosophila and in mitochondrial maintenance in yeast. Most recently, the function
      of rhomboid peptidases has been directly linked to apoptosis. We have solved the
      structure of the rhomboid peptidase from Haemophilus influenzae (hiGlpG) to 2.2-A
      resolution. The phasing for the crystals of hiGlpG was provided mainly by
      molecular replacement, by using the coordinates of the Escherichia coli rhomboid
      (ecGlpG). The structural results on these rhomboid peptidases have allowed us to
      speculate on the catalytic mechanism of substrate cleavage in a membranous
      environment. We have identified the relative disposition of the nucleophilic
      serine to the general base/acid function of the conserved histidine. Modeling a
      tetrapeptide substrate in the context of the rhomboid structure reveals an
      oxyanion hole comprising the side chain of a second conserved histidine and the
      main-chain NH of the nucleophilic serine residue. In both hiGlpG and ecGlpG
      structures, a water molecule occupies this oxyanion hole.

PMID- 17210916
TI  - Cooperation and conflict in microbial biofilms.
AB  - Biofilms, in which cells attach to surfaces and secrete slime (polymeric
      substances), are central to microbial life. Biofilms are often thought to require
      high levels of cooperation because extracellular polymeric substances are a
      shared resource produced by one cell that can be used by others. Here we examine
      this hypothesis by using a detailed individual-based simulation of a biofilm to
      investigate the outcome of evolutionary competitions between strains that differ
      in their level of polymer production. Our model includes a biochemical
      description of the carbon fluxes for growth and polymer production, and it
      explicitly calculates diffusion-reaction effects and the resulting solute
      gradients in the biofilm. An emergent property of these simple but realistic
      mechanistic assumptions is a strong evolutionary advantage to extracellular
      polymer production. Polymer secretion is altruistic to cells above a focal cell:
      it pushes later generations in their lineage up and out into better oxygen
      conditions, but it harms others; polymer production suffocates neighboring
      nonpolymer producers. This property, analogous to vertical growth in plants,
      suggests that polymer secretion provides a strong competitive advantage to cell
      lineages within mixed-genotype biofilms: global cooperation is not required. Our
      model fundamentally changes how biofilms are expected to respond to changing
      social conditions; the presence of multiple strains in a biofilm should promote
      rather than inhibit polymer secretion.

PMID- 17210915
TI  - Baf60c is a nuclear Notch signaling component required for the establishment of
      left-right asymmetry.
AB  - Notch-mediated induction of Nodal at the vertebrate node is a critical step in
      initiating left-right (LR) asymmetry. In mice and zebrafish we show that Baf60c,
      a subunit of the Swi/Snf-like BAF chromatin remodeling complex, is essential for
      establishment of LR asymmetry. Baf60c knockdown mouse embryos fail to activate
      Nodal at the node and also have abnormal node morphology with mixing of crown and
      pit cells. In cell culture, Baf60c is required for Notch-dependent
      transcriptional activation and functions to stabilize interactions between
      activated Notch and its DNA-binding partner, RBP-J. Brg1 is also required for
      these processes, suggesting that BAF complexes are key components of nuclear
      Notch signaling. We propose a critical role for Baf60c in Notch-dependent
      transcription and LR asymmetry.

PMID- 17210917
TI  - A structural rationale for stalling of a replicative DNA polymerase at the most
      common oxidative thymine lesion, thymine glycol.
AB  - Thymine glycol (Tg) is a common product of oxidation and ionizing radiation,
      including that used for cancer treatment. Although Tg is a poor mutagenic lesion,
      it has been shown to present a strong block to both repair and replicative DNA
      polymerases. The 2.65-A crystal structure of a binary complex of the replicative
      RB69 DNA polymerase with DNA shows that the templating Tg is intrahelical and
      forms a regular Watson-Crick base pair with the incorporated A. The C5 methyl
      group protrudes axially from the ring of the damaged pyrimidine and hinders
      stacking of the adjacent 5' template guanine. The position of the displaced 5'
      template guanine is such that the next incoming nucleotide cannot be incorporated
      into the growing primer strand, and it explains why primer extension past the
      lesion is prohibited even though DNA polymerases can readily incorporate an A
      across from the Tg lesion.

PMID- 17210918
TI  - Conservation of B class gene expression in the second whorl of a basal grass and
      outgroups links the origin of lodicules and petals.
AB  - Studies of flower development in core eudicot species have established a central
      role for B class MADS-box genes in specifying petal and stamen identities.
      Similarly in maize and rice, B class genes are essential for lodicule and stamen
      specification, suggesting homology of petals and lodicules and conservation of B
      class gene activity across angiosperms. However, lodicules are grass-specific
      organs with a morphology distinct from petals, thus their true homology to
      eudicot and nongrass monocot floral organs has been a topic of debate. To
      understand the relationship of lodicules to the sterile floral organs of nongrass
      monocots we have isolated and observed the expression of B class genes from a
      basal grass Streptochaeta that diverged before the evolution of lodicules, as
      well as the outgroups Joinvillea and Elegia, which have a typical monocot floral
      plan. Our results support a conserved role for B function genes across the
      angiosperms and provide additional evidence linking the evolution of lodicules
      and second whorl tepal/petals of monocots. The expression data and morphological
      analysis suggest that the function of B class genes should be broadly interpreted
      as required for differentiation of a distinct second floral whorl as opposed to
      specifying petal identity per se.

PMID- 17210919
TI  - Mechanisms underlying the resistance to diet-induced obesity in germ-free mice.
AB  - The trillions of microbes that colonize our adult intestines function
      collectively as a metabolic organ that communicates with, and complements, our
      own human metabolic apparatus. Given the worldwide epidemic in obesity, there is
      interest in how interactions between human and microbial metabolomes may affect
      our energy balance. Here we report that, in contrast to mice with a gut
      microbiota, germ-free (GF) animals are protected against the obesity that
      develops after consuming a Western-style, high-fat, sugar-rich diet. Their
      persistently lean phenotype is associated with increased skeletal muscle and
      liver levels of phosphorylated AMP-activated protein kinase (AMPK) and its
      downstream targets involved in fatty acid oxidation (acetylCoA carboxylase;
      carnitine-palmitoyltransferase). Moreover, GF knockout mice lacking fasting
      induced adipose factor (Fiaf), a circulating lipoprotein lipase inhibitor whose
      expression is normally selectively suppressed in the gut epithelium by the
      microbiota, are not protected from diet-induced obesity. Although GF Fiaf-/-
      animals exhibit similar levels of phosphorylated AMPK as their wild-type
      littermates in liver and gastrocnemius muscle, they have reduced expression of
      genes encoding the peroxisomal proliferator-activated receptor coactivator (Pgc
      1alpha) and enzymes involved in fatty acid oxidation. Thus, GF animals are
      protected from diet-induced obesity by two complementary but independent
      mechanisms that result in increased fatty acid metabolism: (i) elevated levels of
      Fiaf, which induces Pgc-1alpha; and (ii) increased AMPK activity. Together, these
      findings support the notion that the gut microbiota can influence both sides of
      the energy balance equation, and underscore the importance of considering our
      metabolome in a supraorganismal context.

PMID- 17210920
TI  - Modern origin of numerous alternatively spliced human introns from tandem arrays.
AB  - Despite the widespread occurrence of spliceosomal introns in the genomes of
      higher eukaryotes, their origin remains controversial. One model proposes that
      the duplication of small genomic portions could have provided the boundaries for
      new introns. If this mechanism has occurred recently, the 5' and 3' boundaries of
      each resulting intron should display distinctive sequence similarity. Here, we
      report that the human genome contains an excess of introns with perfect matching
      sequences at boundaries. One-third of these introns interrupt the protein-coding
      sequences of known genes. Introns with the best-matching boundaries are
      invariably found in tandem arrays of direct repeats. Sequence analysis of the
      arrays indicates that many intron-breeding repeats have disseminated in several
      genes at different times during human evolution. A comparison with orthologous
      regions in mouse and chimpanzee suggests a young age for the human introns with
      the most-similar boundaries. Finally, we show that these human introns are
      alternatively spliced with exceptionally high frequency. Our study indicates that
      genomic duplication has been an important mode of intron gain in mammals. The
      alternative splicing of transcripts containing these intron-breeding repeats may
      provide the plasticity required for the rapid evolution of new human proteins.

PMID- 17210921
TI  - Combination angiostatic therapy completely inhibits ocular and tumor
      angiogenesis.
AB  - Angiostatic therapies designed to inhibit neovascularization associated with
      multiple pathological conditions have only been partially successful; complete
      inhibition has not been achieved. We demonstrate synergistic effects of combining
      angiostatic molecules that target distinct aspects of the angiogenic process,
      resulting in the complete inhibition of neovascular growth associated with
      development, ischemic retinopathy, and tumor growth, with little or no effect on
      normal, mature tissue vasculature. Tumor vascular obliteration using combination
      angiostatic therapy was associated with reduced tumor mass and increased survival
      in a rat 9L gliosarcoma model, whereas individual monotherapies were ineffective.
      Significant compensatory up-regulation of several proangiogenic factors was
      observed after treatment with a single angiostatic agent. In contrast, treatment
      with combination angiostatic therapy significantly reduced compensatory up
      regulation. Therapies that combine angiostatic molecules targeting multiple,
      distinct aspects of the angiogenic process may represent a previously
      uncharacterized paradigm for the treatment of many devastating diseases with
      associated pathological neovascularization.

PMID- 17210922
TI  - Noise can play an organizing role for the recurrent dynamics in excitable media.
AB  - We analyze patterns of recurrent activity in a prototypical model of an excitable
      medium in the presence of noise. Without noise, this model robustly predicts the
      existence of spiral waves as the only recurrent patterns in two dimensions. With
      small noise, however, we found that this model is also capable of generating
      coherent target patterns, another type of recurrent activity that is widely
      observed experimentally. These patterns remain essentially deterministic despite
      the presence of the noise, yet their existence is impossible without it. Their
      degree of coherence can also be made arbitrarily high for wide ranges of the
      parameters, which does not require fine-tuning. Our findings demonstrate the need
      to reexamine current modeling approaches to active biological media.

PMID- 17210923
TI  - SIBLING expression patterns in duct epithelia reflect the degree of metabolic
      activity.
AB  - The SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family of
      secreted glycophosphoproteins includes bone sialoprotein (BSP), dentin matrix
      protein-1 (DMP1), dentin sialophosphoprotein (DSPP), osteopontin (OPN), and
      matrix extracellular phosphoglycoprotein (MEPE). For many years, they were
      thought in normal adults to essentially be limited to metabolically active
      mesenchymal cells that assembled the mineralized matrices of bones and teeth.
      Over the last decade they have also been upregulated in a variety of tumors.
      Three of these proteins (BSP, OPN, and DMP1) have been shown to interact with
      three matrix metalloproteinases (MMP-2, MMP-3, and MMP-9, respectively).
      Recently, all five SIBLINGs and their MMP partners when known were observed in
      specific elements of normal ductal epithelia in salivary gland and kidney. We
      have hypothesized that the SIBLINGs and their MMP partners may be expressed in
      ductal cells with high metabolic activity. In this paper, we show that all the
      SIBLINGs (except MEPE) and their MMP partners are expressed in the metabolically
      active epithelia of human eccrine sweat gland duct but not in the more passive
      ductal cells of the macaque (monkey) lacrimal gland. It is hypothesized that MEPE
      expression may be limited to cells involved in active phosphate transport. This
      manuscript contains online supplemental material at http://www.jhc.org. Please
      visit this article online to view these materials.

PMID- 17210924
TI  - Nestin expression in adult and developing human kidney.
AB  - Nestin is considered a marker of neurogenic and myogenic precursor cells. Its
      arrangement is regulated by cyclin-dependent kinase 5 (CDK5), which is expressed
      in murine podocytes. We investigated nestin expression in human adult and fetal
      kidney as well as CDK5 presence in adult human podocytes. Confocal microscopy
      demonstrated that adult glomeruli display nestin immunoreactivity in vimentin
      expressing cells with the podocyte morphology and not in cells bearing the
      endothelial marker CD31. Glomerular nestin-positive cells were CDK5
      immunoreactive as well. Western blotting of the intermediate filament-enriched
      cytoskeletal fraction and coimmunoprecipitation of nestin with anti-CDK5
      antibodies confirmed these results. Nestin was also detected in developing
      glomeruli within immature podocytes and a few other cells. Confocal microscopy of
      experiments conducted with antibodies against nestin and endothelial markers
      demonstrated that endothelial cells belonging to capillaries invading the lower
      cleft of S-shaped bodies and the immature glomeruli were nestin immunoreactive.
      Similar experiments carried out with antibodies raised against nestin and alpha
      smooth muscle actin showed that the first mesangial cells that populate the
      developing glomeruli expressed nestin. In conclusion, nestin is expressed in the
      human kidney from the first steps of glomerulogenesis within podocytes,
      mesangial, and endothelial cells. This expression, restricted to podocytes in
      mature glomeruli, appears associated with CDK5.

PMID- 17210925
TI  - Nitric oxide synthase immunoreactivity and NADPH-d histochemistry in the enteric
      nervous system of Sarda breed sheep with different PrP genotypes in whole-mount
      and cryostat preparations.
AB  - Until now, significant differences in the neurochemical pattern of enteric
      neurons have been demonstrated in all species studied; however, some strong
      similarities also occur across species, such as the occurrence of nitric oxide
      synthase immunoreactivity (NOS-IR) in inhibitory motor neurons to muscle. In
      consideration of the insufficient data regarding the enteric nervous system (ENS)
      of sheep, we investigated the myenteric plexus and submucosal plexus of the ovine
      ileum. Since the pivotal role of the ENS in the early pathogenesis of sheep
      scrapie, the "prototype" of prion diseases, has been suggested, we have focused
      our observations also on the host's PrP genotype. We have studied the morphology
      and distribution of NOS-IR neurons and their relationships with the enteric glia
      in whole-mount preparations and in cryostat sections. NOS-IR neurons, always
      encircled by glial processes, were located in both plexuses. Many NOS-IR fibers
      were seen in the circular muscle layer, in the submucosa, and in the mucosa. In
      the submucosa they were close to the lymphoid tissue. No differences in the
      distribution and percentage of NOS-IR fibers and neurons were observed among
      sheep carrying different PrP genotype, thus making unlikely their contribution in
      the determinism of susceptibility/resistance to scrapie infection.

PMID- 17210926
TI  - Comparative genomic analysis identifies an evolutionary shift of vomeronasal
      receptor gene repertoires in the vertebrate transition from water to land.
AB  - Two evolutionarily unrelated superfamilies of G-protein coupled receptors, V1Rs
      and V2Rs, bind pheromones and "ordinary" odorants to initiate vomeronasal
      chemical senses in vertebrates, which play important roles in many aspects of an
      organism's daily life such as mating, territoriality, and foraging. To study the
      macroevolution of vomeronasal sensitivity, we identified all V1R and V2R genes
      from the genome sequences of 11 vertebrates. Our analysis suggests the presence
      of multiple V1R and V2R genes in the common ancestor of teleost fish and
      tetrapods and reveals an exceptionally large among-species variation in the sizes
      of these gene repertoires. Interestingly, the ratio of the number of intact V1R
      genes to that of V2R genes increased by approximately 50-fold as land vertebrates
      evolved from aquatic vertebrates. A similar increase was found for the ratio of
      the number of class II odorant receptor (OR) genes to that of class I genes, but
      not in other vertebrate gene families. Because V1Rs and class II ORs have been
      suggested to bind to small airborne chemicals, whereas V2Rs and class I ORs
      recognize water-soluble molecules, these increases reflect a rare case of
      adaptation to terrestrial life at the gene family level. Several gene families
      known to function in concert with V2Rs in the mouse are absent outside rodents,
      indicating rapid changes of interactions between vomeronasal receptors and their
      molecular partners. Taken together, our results demonstrate the exceptional
      evolutionary fluidity of vomeronasal receptors, making them excellent targets for
      studying the molecular basis of physiological and behavioral diversity and
      adaptation.

PMID- 17210927
TI  - Predicting tissue-specific enhancers in the human genome.
AB  - Determining how transcriptional regulatory signals are encoded in vertebrate
      genomes is essential for understanding the origins of multicellular complexity;
      yet the genetic code of vertebrate gene regulation remains poorly understood. In
      an attempt to elucidate this code, we synergistically combined genome-wide gene
      expression profiling, vertebrate genome comparisons, and transcription factor
      binding-site analysis to define sequence signatures characteristic of candidate
      tissue-specific enhancers in the human genome. We applied this strategy to
      microarray-based gene expression profiles from 79 human tissues and identified
      7187 candidate enhancers that defined their flanking gene expression, the
      majority of which were located outside of known promoters. We cross-validated
      this method for its ability to de novo predict tissue-specific gene expression
      and confirmed its reliability in 57 of the 79 available human tissues, with an
      average precision in enhancer recognition ranging from 32% to 63% and a
      sensitivity of 47%. We used the sequence signatures identified by this approach
      to successfully assign tissue-specific predictions to approximately 328,000 human
      mouse conserved noncoding elements in the human genome. By overlapping these
      genome-wide predictions with a data set of enhancers validated in vivo, in
      transgenic mice, we were able to confirm our results with a 28% sensitivity and
      50% precision. These results indicate the power of combining complementary
      genomic data sets as an initial computational foray into a global view of tissue
      specific gene regulation in vertebrates.

PMID- 17210928
TI  - Reductive evolution and niche adaptation inferred from the genome of
      Mycobacterium ulcerans, the causative agent of Buruli ulcer.
AB  - Mycobacterium ulcerans is found in aquatic ecosystems and causes Buruli ulcer in
      humans, a neglected but devastating necrotic disease of subcutaneous tissue that
      is rampant throughout West and Central Africa. Here, we report the complete 5.8
      Mb genome sequence of M. ulcerans and show that it comprises two circular
      replicons, a chromosome of 5632 kb and a virulence plasmid of 174 kb. The plasmid
      is required for production of the polyketide toxin mycolactone, which provokes
      necrosis. Comparisons with the recently completed 6.6-Mb genome of Mycobacterium
      marinum revealed >98% nucleotide sequence identity and genome-wide synteny.
      However, as well as the plasmid, M. ulcerans has accumulated 213 copies of the
      insertion sequence IS2404, 91 copies of IS2606, 771 pseudogenes, two
      bacteriophages, and multiple DNA deletions and rearrangements. These data
      indicate that M. ulcerans has recently evolved via lateral gene transfer and
      reductive evolution from the generalist, more rapid-growing environmental species
      M. marinum to become a niche-adapted specialist. Predictions based on genome
      inspection for the production of modified mycobacterial virulence factors, such
      as the highly abundant phthiodiolone lipids, were confirmed by structural
      analyses. Similarly, 11 protein-coding sequences identified as M. ulcerans
      specific by comparative genomics were verified as such by PCR screening a diverse
      collection of 33 strains of M. ulcerans and M. marinum. This work offers
      significant insight into the biology and evolution of mycobacterial pathogens and
      is an important component of international efforts to counter Buruli ulcer.

PMID- 17210929
TI  - Characterization and predictive discovery of evolutionarily conserved mammalian
      alternative promoters.
AB  - Recent studies suggest that surprisingly many mammalian genes have alternative
      promoters (APs); however, their biological roles, and the characteristics that
      distinguish them from single promoters (SPs), remain poorly understood. We
      constructed a large data set of evolutionarily conserved promoters, and used it
      to identify sequence features, functional associations, and expression patterns
      that differ by promoter type. The four promoter categories CpG-rich APs, CpG-poor
      APs, CpG-rich SPs, and CpG-poor SPs each show characteristic strengths and
      patterns of sequence conservation, frequencies of putative transcription-related
      motifs, and tissue and developmental stage expression preferences. APs display
      substantially higher sequence conservation than SPs and CpG-poor promoters than
      CpG-rich promoters. Among CpG-poor promoters, APs and SPs show sharply
      contrasting developmental stage preferences and TATA box frequencies. We
      developed a discriminator to computationally predict promoter type, verified its
      accuracy through experimental tests that incorporate a novel method for
      deconvolving mixed sequence traces, and used it to find several new APs. The
      discriminator predicts that almost half of all mammalian genes have
      evolutionarily conserved APs. This high frequency of APs, together with the
      strong purifying selection maintaining them, implies a crucial role in expanding
      the expression diversity of the mammalian genome.

PMID- 17210930
TI  - A tale of two templates: automatically resolving double traces has many
      applications, including efficient PCR-based elucidation of alternative splices.
AB  - Trace Recalling is a novel method for deconvoluting double traces that result
      from simultaneously sequencing two DNA templates. Trace Recalling identifies up
      to two bases at each position of such a trace. The resulting ambiguity sequence
      is aligned to the genome, identifying one template sequence. A second template
      sequence is then inferred from this alignment. This technique makes possible many
      exciting biological applications. Here we present two such applications,
      alternate splice finding and elucidation of multiple insertion sites in a random
      insertional mutagenesis library. Our results demonstrate that RT-PCR followed by
      Trace Recalling is a more efficient and cost effective way to find alternate
      splices than traditional methods. We also present a method for mapping double
      insertion events in a random insertional-mutagenesis library.

PMID- 17210931
TI  - Widespread mRNA polyadenylation events in introns indicate dynamic interplay
      between polyadenylation and splicing.
AB  - mRNA polyadenylation and pre-mRNA splicing are two essential steps for the
      maturation of most human mRNAs. Studies have shown that some genes generate mRNA
      variants involving both alternative polyadenylation and alternative splicing.
      Polyadenylation in introns can lead to conversion of an internal exon to a 3'
      terminal exon, which is termed composite terminal exon, or usage of a 3' terminal
      exon that is otherwise skipped, which is termed skipped terminal exon. Using
      cDNA/EST and genome sequences, we identified polyadenylation sites in introns for
      all currently known human genes. We found that approximately 20% human genes have
      at least one intronic polyadenylation event that can potentially lead to mRNA
      variants, most of which encode different protein products. The conservation of
      human intronic poly(A) sites in mouse and rat genomes is lower than that of
      poly(A) sites in 3'-most exons. Quantitative analysis of a number of mRNA
      variants generated by intronic poly(A) sites suggests that the intronic
      polyadenylation activity can vary under different cellular conditions for most
      genes. Furthermore, we found that weak 5' splice site and large intron size are
      the determining factors controlling the usage of composite terminal exon poly(A)
      sites, whereas skipped terminal exon poly(A) sites tend to be associated with
      strong polyadenylation signals. Thus, our data indicate that dynamic interplay
      between polyadenylation and splicing leads to widespread polyadenylation in
      introns and contributes to the complexity of transcriptome in the cell.

PMID- 17210935
TI  - Is high and growing spending on cancer treatment and prevention harmful to the
      United States economy?

PMID- 17210933
TI  - Ductal carcinoma in situ in BRCA mutation carriers.
AB  - PURPOSE: The current literature suggests that ductal carcinoma in situ (DCIS) of
      the breast is infrequently diagnosed in patients with BRCA germline mutations. We
      studied women at high risk of hereditary breast cancer syndromes who underwent
      testing for BRCA1 and BRCA2 to estimate DCIS prevalence and incidence in known
      BRCA-positive women compared with high-risk women who were mutation negative.
      METHODS: We analyzed breast event outcomes in a retrospective cohort of 129 BRCA
      positive and 269 BRCA-negative women undergoing genetic testing for a BRCA
      mutation between September 1996 and December 2003 at University of California,
      San Francisco. We estimated the frequency of DCIS and invasive cancer and time to
      breast events from birth using a Cox proportional hazard model for competing
      risks. Histologic grade of DCIS was also compared between groups. RESULTS: Among
      BRCA carriers, 48 (37%) had DCIS (with or without invasive cancer) compared with
      92 noncarriers (34%). Univariate analysis showed that both DCIS and invasive
      cancer had an earlier onset in mutation carriers than in noncarriers, although on
      a per-woman basis, this difference was not statistically significant. High-grade
      DCIS was more common in BRCA1 mutation carriers than in patients without a
      mutation (P = .02). CONCLUSION: DCIS is equally as prevalent in patients who
      carry deleterious BRCA mutations as in high familial-risk women who are
      noncarriers, but occurs at an earlier age. Our results argue for the
      consideration of DCIS as a criterion for BRCA risk assessments with appropriate
      weighting in prediction models such as BRCAPRO.

PMID- 17210932
TI  - Curated genome annotation of Oryza sativa ssp. japonica and comparative genome
      analysis with Arabidopsis thaliana.
AB  - We present here the annotation of the complete genome of rice Oryza sativa L.
      ssp. japonica cultivar Nipponbare. All functional annotations for proteins and
      non-protein-coding RNA (npRNA) candidates were manually curated. Functions were
      identified or inferred in 19,969 (70%) of the proteins, and 131 possible npRNAs
      (including 58 antisense transcripts) were found. Almost 5000 annotated protein
      coding genes were found to be disrupted in insertional mutant lines, which will
      accelerate future experimental validation of the annotations. The rice loci were
      determined by using cDNA sequences obtained from rice and other representative
      cereals. Our conservative estimate based on these loci and an extrapolation
      suggested that the gene number of rice is approximately 32,000, which is smaller
      than previous estimates. We conducted comparative analyses between rice and
      Arabidopsis thaliana and found that both genomes possessed several lineage
      specific genes, which might account for the observed differences between these
      species, while they had similar sets of predicted functional domains among the
      protein sequences. A system to control translational efficiency seems to be
      conserved across large evolutionary distances. Moreover, the evolutionary process
      of protein-coding genes was examined. Our results suggest that natural selection
      may have played a role for duplicated genes in both species, so that duplication
      was suppressed or favored in a manner that depended on the function of a gene.

PMID- 17210936
TI  - How should we pay the piper when he's calling the tune? On the long-term
      affordability of cancer care in the United States.

PMID- 17210937
TI  - Cost of cancer care: issues and implications.
AB  - Medical technology is increasingly costly in most fields of clinical medicine.
      Oncology has not been spared from issues related to cost, in part resulting from
      the tremendous scientific progress that has lead to new tools for diagnosis,
      treatment, and follow-up of our patients. The increasing cost of health care in
      general (and cancer care in particular) raises complex questions related to its
      effects on our economy and the citizens of our society. This article reviews the
      macroeconomic principles and individual behaviors that govern medical spending,
      and examines how cost disproportionately affects various populations. Our overall
      goal is to frame debate about health policy concerns that influence the clinical
      practice of oncology.

PMID- 17210938
TI  - Costs of cancer care: a view from the centers for Medicare and Medicaid services.
AB  - Fee-for-service Medicare pays for a very substantial portion of all cancer care
      delivered in the United States. By virtue of its size and visibility, its payment
      policies at times also influence those of other health care payers. As a result,
      Medicare affects both the overall economics and the incentive structures of
      oncology care. Three aspects of how Medicare finances cancer care are
      particularly germane to the issue of costs. First, Medicare finances all aspects
      of cancer care in independent payment units, paying separately for physician
      services, laboratory tests, procedures, imaging, radiation, drug administration,
      and drugs. Second, Medicare is currently managing and monitoring a very
      substantial overhaul in payment for cancer care, which aims to reduce or
      eliminate incentives that have favored aggressive and costly treatments in
      clinical situations where alternative therapeutic approaches might have been
      equivalent or preferable. Third, Medicare is trying to increase the focus on care
      quality and transparency, as improved efficiency and greater value is needed if
      costs of care are to be contained. Understanding these three aspects of cancer
      care financing can help clarify what Medicare is capable of doing to control the
      rising costs that are occurring in cancer today.

PMID- 17210939
TI  - European perspective on the costs and cost-effectiveness of cancer therapies.
AB  - In Europe, the vast majority of the costs of cancer therapy fall on third-party
      payers, normally the government, or sickness funds. Therefore, the main focus of
      cost-effectiveness studies is to assist payers in deciding whether new therapies
      are worthwhile, despite their high cost. Drug budgets are regulated in most
      European countries. The main form of central control is price setting, with some
      form of reference pricing being the most common approach. This sets the price of
      drugs, either to an international standard, or to a common price for drugs in the
      same group or cluster. At the hospital level, the main control over cancer drugs
      is the hospital formulary. Studies have shown a wide variation among European
      countries in access to cancer drugs. Explanations for these variations include
      differences in research funding, the drug approval process, the role of health
      economics in decision making, and budgetary issues. Several countries in Europe
      now require economic data in making decisions about the reimbursement of new
      drugs. An examination of decisions made by the National Institute for Health and
      Clinical Excellence in the United Kingdom suggests that cancer drugs have fared
      quite well, with most recommendations being positive. This could be because of
      the seriousness of the health condition and the lack of alternative therapies for
      some cancer patients. If the policy of requesting cost-effectiveness evidence for
      pricing and reimbursement decisions becomes more popular, a major implication for
      the pharmaceutical industry is that studies should be conducted during phase III
      of clinical development to generate the required data.

PMID- 17210940
TI  - Interpreting the economic literature in oncology.
AB  - New treatment options provide hope for patients with localized and advanced
      cancer. However, these advances are associated with cost, both in terms of
      treatment-related expenditures and effects on quality of life. It is important
      that patients, physicians, insurers, and policymakers understand the relationship
      between costs and outcomes of new cancer treatments. Various methods of cost
      analysis can provide a structured manner to assess cost. Cost-effectiveness
      analysis (CEA) compares the cost of the intervention with the effect, resulting
      in a cost per effect (eg, cost per year of life gained) that can be compared
      across interventions. In this article, we review three recent CEAs in the
      oncology literature, including chemoprevention in breast cancer, adjuvant
      endocrine therapy in early-stage breast cancer, and salvage chemotherapy in
      advanced ovarian cancer. The important elements of CEA, including the
      recommendations of the US Public Health Service Panel on Cost Effectiveness in
      Health and Medicine as they relate to cancer treatments, are discussed. Many well
      done CEAs in cancer treatment have been performed during the last decade. As with
      clinical trials, the rigor and methods of the analysis are critical to the
      reliability of the results. Therapies with high cost and small incremental
      improvement in survival and/or quality of life may find it difficult to meet the
      societal thresholds for what is considered cost effective. CEA is a method to
      assess the cost and effect of cancer treatments, providing important insights
      into the best use (ie, obtaining the most value for) of health care expenditures.
      As the literature indicates, one must be cognizant of the fact that there can be
      extraordinary costs associated with some newer cancer therapies that provide
      small incremental clinical benefit. Better understanding of the cancer economic
      literature can help lead to an informed dialogue on the health policy
      implications of resource allocation in cancer care.

PMID- 17210941
TI  - Use of modeling to evaluate the cost-effectiveness of cancer screening programs.
AB  - Cost-effectiveness analysis (CEA) is an analytic tool that provides a framework
      for comparing the health benefits and resource expenditures associated with
      competing medical and public health interventions, thereby allowing decision
      makers to identify interventions that yield the greatest amount of health, given
      their resource constraints. Models are important components of most, if not all,
      CEAs, and they play a key role in evaluating the cost-effectiveness of cancer
      screening programs, in particular. In this article, we describe the basic types
      of models used to evaluate cancer screening programs and provide examples of the
      use of models in CEAs and to guide cancer screening policy. Finally, we offer
      some suggestions for important concepts to consider when interpreting model
      results.

PMID- 17210942
TI  - Economics of new oncology drug development.
AB  - PURPOSE: Review existing studies and provide new results on the development,
      regulatory, and market aspects of new oncology drug development. METHODS: We
      utilized data from the US Food and Drug Administration (FDA), company surveys,
      and publicly available commercial business intelligence databases on new oncology
      drugs approved in the United States and on investigational oncology drugs to
      estimate average development and regulatory approval times, clinical approval
      success rates, first-in-class status, and global market diffusion. RESULTS: We
      found that approved new oncology drugs to have a disproportionately high share of
      FDA priority review ratings, of orphan drug designations at approval, and of
      drugs that were granted inclusion in at least one of the FDA's expedited access
      programs. US regulatory approval times were shorter, on average, for oncology
      drugs (0.5 years), but US clinical development times were longer on average (1.5
      years). Clinical approval success rates were similar for oncology and other
      drugs, but proportionately more of the oncology failures reached expensive late
      stage clinical testing before being abandoned. In relation to other drugs, new
      oncology drug approvals were more often first-in-class and diffused more widely
      across important international markets. CONCLUSION: The market success of
      oncology drugs has induced a substantial amount of investment in oncology drug
      development in the last decade or so. However, given the great need for further
      progress, the extent to which efforts to develop new oncology drugs will grow
      depends on future public-sector investment in basic research, developments in
      translational medicine, and regulatory reforms that advance drug-development
      science.

PMID- 17210943
TI  - Cancer care, money, and the value of life: whose justice? Which rationality?
AB  - Cost-containment in oncology is a moral issue. While economists use the word
      "rationing" to describe all limitations on resource utilization that result from
      human choice, the ordinary language distinction between allocation and rationing
      is morally meaningful and can help oncologists to determine their proper moral
      role in cost-containment. It is argued that oncologists should not be required to
      ration at the bedside, nor should they be given financial incentives to practice
      frugally, nor should they be subjected to a variety of bureaucratic mechanisms to
      control costs indirectly. In addition, it is argued that the fact that treatments
      have a price does not logically imply that patients have a price. Cost
      effectiveness analysis is often suggested as a means of deciding how best to
      allocate resources, but some of its many ethical limitations are discussed. The
      alternative is an open, public, participatory process about how to ration care,
      abandoning the formulaic pretenses of cost-effectiveness analysis, but with a
      commitment to reason, good will, and common sense. Oncologists would then be free
      to advocate for their patients within the constraints imposed by this public
      process.

PMID- 17210944
TI  - Value of high-cost cancer care: a behavioral science perspective.
AB  - Concerns about the high costs of cancer care have led to a renewed interest in
      understanding how patients value the outcomes of care. Psychologists, economists,
      and others have highlighted some of the ways in which patients and caregivers
      perceive and make treatment decisions. Prospect theory is the predominant
      framework for understanding decisions made in situations where the outcomes of
      each choice are uncertain. Prospect theory assumes that a patient values the
      outcomes of care not in absolute terms, such as years of life saved, but as
      deviations from the patient's point of reference. This article discusses some of
      the implications of this notion, along with discussing differences among people
      in their reference points. These and other considerations from the psychology of
      decision making help to clarify why some patients might be inclined to seek
      expensive or risky treatments in the hopes of achieving benefits that others
      might consider not worthwhile. An appreciation of these psychological issues
      might improve the quality of debates concerning the rising costs of cancer care.

PMID- 17210945
TI  - Cost of cancer care: the patient perspective.
AB  - The diagnosis of cancer, along with subsequent related care, imposes a number of
      burdens on patients--physical, emotional, and financial. The financial expenses
      incurred extend well beyond the cost of medication, surgery, and related
      treatments. While these important issues warrant attention, patients also need
      assistance dealing with the indirect costs of cancer care, such as
      transportation, child care, and lost wages. There is an urgent need to improve
      the current inconsistent--sometimes nonexistent--methods used to inform patients
      about costs of cancer care as well as to provide them with appropriate assistance
      managing the costs and overall burden of cancer. Health care providers, patient
      advocates, agencies, and insurers have the responsibility and opportunity to
      provide leadership in this process. Most importantly, limited ability to address
      any of the expenses brought on by cancer should not prevent any patient from
      receiving necessary care.

PMID- 17210946
TI  - Medical oncologists' views on communicating with patients about chemotherapy
      costs: a pilot survey.
AB  - PURPOSE: As chemotherapy costs escalate, financial concerns have become relevant
      for more cancer patients. Yet, little is known about how oncologists communicate
      with patients about coping with chemotherapy treatment costs. METHODS: To
      understand how medical oncologists view these issues, we developed a survey
      eliciting their attitudes and behaviors surrounding discussing costs of therapy
      in the context of treatment decision making. The survey was piloted at a national
      meeting and then mailed to a random sample of actively practicing 2005 American
      Society of Clinical Oncology members in the 50 United States. Survey items used a
      5-point Likert scale designed to elicit oncologists' practices and attitudes
      regarding discussion of chemotherapy costs with patients. The first survey wave
      also included two clinical vignettes about hypothetical patients contemplating
      treatment with high-cost regimens. RESULTS: Of 530 mailed surveys, 167 were
      returned for an overall response rate of 31.5%. Most oncologists reported
      knowledge of their patients' financial well-being: 15% all of the time, 39% most
      of the time, 33% some of the time, and 13% rarely/none of the time. There was
      substantial variation in oncologists' attitudes toward discussing chemotherapy
      costs with patients: 42% did so always or most of the time, 32% sometimes did,
      and 26% rarely or never did. Most oncologists (80%) felt that it was important to
      be explicit about the impact of treatment choices on patients' finances. However,
      20% maintained that costs play no role in clinical encounters, and 31% reported a
      high degree of discomfort in discussing costs with patients. Referral to support
      staff for these discussions was common. Only a few oncologists (16%) acknowledged
      omitting treatment options on the basis of their perceptions of patients' ability
      to afford treatment. CONCLUSION: There is important heterogeneity in medical
      oncologists' attitudes toward discussing chemotherapy treatment costs with
      patients. Mismatch between physician and patient viewpoints has the potential to
      result in miscommunication and suboptimally informed treatment decisions.

PMID- 17210947
TI  - Novel cell death program leads to neutrophil extracellular traps.
AB  - Neutrophil extracellular traps (NETs) are extracellular structures composed of
      chromatin and granule proteins that bind and kill microorganisms. We show that
      upon stimulation, the nuclei of neutrophils lose their shape, and the eu- and
      heterochromatin homogenize. Later, the nuclear envelope and the granule membranes
      disintegrate, allowing the mixing of NET components. Finally, the NETs are
      released as the cell membrane breaks. This cell death process is distinct from
      apoptosis and necrosis and depends on the generation of reactive oxygen species
      (ROS) by NADPH oxidase. Patients with chronic granulomatous disease carry
      mutations in NADPH oxidase and cannot activate this cell-death pathway or make
      NETs. This novel ROS-dependent death allows neutrophils to fulfill their
      antimicrobial function, even beyond their lifespan.

PMID- 17210948
TI  - Puf3p, a Pumilio family RNA binding protein, localizes to mitochondria and
      regulates mitochondrial biogenesis and motility in budding yeast.
AB  - Puf3p binds preferentially to messenger RNAs (mRNAs) for nuclear-encoded
      mitochondrial proteins. We find that Puf3p localizes to the cytosolic face of the
      mitochondrial outer membrane. Overexpression of PUF3 results in reduced
      mitochondrial respiratory activity and reduced levels of Pet123p, a protein
      encoded by a Puf3p-binding mRNA. Puf3p levels are reduced during the diauxic
      shift and growth on a nonfermentable carbon source, conditions that stimulate
      mitochondrial biogenesis. These findings support a role for Puf3p in
      mitochondrial biogenesis through effects on mRNA interactions. In addition, Puf3p
      links the mitochore, a complex required for mitochondrial-cytoskeletal
      interactions, to the Arp2/3 complex, the force generator for actin-dependent, bud
      directed mitochondrial movement. Puf3p, the mitochore, and the Arp2/3 complex
      coimmunoprecipitate and have two-hybrid interactions. Moreover, deletion of PUF3
      results in reduced interaction between the mitochore and the Arp2/3 complex and
      defects in mitochondrial morphology and motility similar to those observed in
      Arp2/3 complex mutants. Thus, Puf3p is a mitochondrial protein that contributes
      to the biogenesis and motility of the organelle.

PMID- 17210949
TI  - Nuclear repositioning of the VSG promoter during developmental silencing in
      Trypanosoma brucei.
AB  - Interphase nuclear repositioning of chromosomes has been implicated in the
      epigenetic regulation of RNA polymerase (pol) II transcription. However, little
      is known about the nuclear position-dependent regulation of RNA pol I-transcribed
      loci. Trypanosoma brucei is an excellent model system to address this question
      because its two main surface protein genes, procyclin and variant surface
      glycoprotein (VSG), are transcribed by pol I and undergo distinct transcriptional
      activation or downregulation events during developmental differentiation.
      Although the monoallelically expressed VSG locus is exclusively localized to an
      extranucleolar body in the bloodstream form, in this study, we report that
      nonmutually exclusive procyclin genes are located at the nucleolar periphery.
      Interestingly, ribosomal DNA loci and pol I transcription activity are restricted
      to similar perinucleolar positions. Upon developmental transcriptional
      downregulation, however, the active VSG promoter selectively undergoes a rapid
      and dramatic repositioning to the nuclear envelope. Subsequently, the VSG
      promoter region was subjected to chromatin condensation. We propose a model
      whereby the VSG expression site pol I promoter is selectively targeted by
      temporal nuclear repositioning during developmental silencing.

PMID- 17210950
TI  - The AAA+ protein ATAD3 has displacement loop binding properties and is involved
      in mitochondrial nucleoid organization.
AB  - Many copies of mammalian mitochondrial DNA contain a short triple-stranded
      region, or displacement loop (D-loop), in the major noncoding region. In the 35
      years since their discovery, no function has been assigned to mitochondrial D
      loops. We purified mitochondrial nucleoprotein complexes from rat liver and
      identified a previously uncharacterized protein, ATAD3p. Localization studies
      suggested that human ATAD3 is a component of many, but not all, mitochondrial
      nucleoids. Gene silencing of ATAD3 by RNA interference altered the structure of
      mitochondrial nucleoids and led to the dissociation of mitochondrial DNA
      fragments held together by protein, specifically, ones containing the D-loop
      region. In vitro, a recombinant fragment of ATAD3p bound to supercoiled DNA
      molecules that contained a synthetic D-loop, with a marked preference over
      partially relaxed molecules with a D-loop or supercoiled DNA circles. These
      results suggest that mitochondrial D-loops serve to recruit ATAD3p for the
      purpose of forming or segregating mitochondrial nucleoids.

PMID- 17210952
TI  - Hwang case review committee misses the mark.

PMID- 17210951
TI  - The Golgi-resident protease Kex2 acts in conjunction with Prm1 to facilitate cell
      fusion during yeast mating.
AB  - The molecular machines that mediate cell fusion are unknown. Previously, we
      identified a multispanning transmembrane protein, Prm1 (pheromone-regulated
      membrane protein 1), that acts during yeast mating (Heiman, M.G., and P. Walter.
      2000. J. Cell Biol. 151:719-730). Without Prm1, a substantial fraction of mating
      pairs arrest with their plasma membranes tightly apposed yet unfused. In this
      study, we show that lack of the Golgi-resident protease Kex2 strongly enhances
      the cell fusion defect of Prm1-deficient mating pairs and causes a mild fusion
      defect in otherwise wild-type mating pairs. Lack of the Kex1 protease but not the
      Ste13 protease results in similar defects. Deltakex2 and Deltakex1 fusion defects
      were suppressed by osmotic support, a trait shared with mutants defective in cell
      wall remodeling. In contrast, other cell wall mutants do not enhance the
      Deltaprm1 fusion defect. Electron microscopy of Deltakex2-derived mating pairs
      revealed novel extracellular blebs at presumptive sites of fusion. Kex2 and Kex1
      may promote cell fusion by proteolytically processing substrates that act in
      parallel to Prm1 as an alternative fusion machine, as cell wall components, or
      both.

PMID- 17210954
TI  - The origin of insect thermoregulatory studies.

PMID- 17210955
TI  - Going wild: what a global small-animal tracking system could do for experimental
      biologists.
AB  - Tracking animals over large temporal and spatial scales has revealed invaluable
      and spectacular biological information, particularly when the paths and fates of
      individuals can be monitored on a global scale. However, only large animals
      (greater than approximately 300 g) currently can be followed globally because of
      power and size constraints on the tracking devices. And yet the vast majority of
      animals is small. Tracking small animals is important because they are often part
      of evolutionary and ecological experiments, they provide important ecosystem
      services and they are of conservation concern or pose harm to human health. Here,
      we propose a small-animal satellite tracking system that would enable the global
      monitoring of animals down to the size of the smallest birds, mammals (bats),
      marine life and eventually large insects. To create the scientific framework
      necessary for such a global project, we formed the ICARUS initiative
      (www.IcarusInitiative.org), the International Cooperation for Animal Research
      Using Space. ICARUS also highlights how small-animal tracking could address some
      of the ;Grand Challenges in Environmental Sciences' identified by the US National
      Academy of Sciences, such as the spread of infectious diseases or the
      relationship between biological diversity and ecosystem functioning. Small-animal
      tracking would allow the quantitative assessment of dispersal and migration in
      natural populations and thus help solve enigmas regarding population dynamics,
      extinctions and invasions. Experimental biologists may find a global small-animal
      tracking system helpful in testing, validating and expanding laboratory-derived
      discoveries in wild, natural populations. We suggest that the relatively modest
      investment into a global small-animal tracking system will pay off by providing
      unprecedented insights into both basic and applied nature. Tracking small animals
      over large spatial and temporal scales could prove to be one of the most powerful
      techniques of the early 21st century, offering potential solutions to a wide
      range of biological and societal questions that date back two millennia to the
      Greek philosopher Aristotle's enigma about songbird migration. Several of the
      more recent Grand Challenges in Environmental Sciences, such as the regulation
      and functional consequences of biological diversity or the surveillance of the
      population ecology of zoonotic hosts, pathogens or vectors, could also be
      addressed by a global small-animal tracking system. Our discussion is intended to
      contribute to an emerging groundswell of scientific support to make such a new
      technological system happen.

PMID- 17210953
TI  - Diet and risk of ovarian cancer in the California Teachers Study cohort.
AB  - Dietary phytochemical compounds, including isoflavones and isothiocyanates, may
      inhibit cancer development but have not yet been examined in prospective
      epidemiologic studies of ovarian cancer. The authors have investigated the
      association between consumption of these and other nutrients and ovarian cancer
      risk in a prospective cohort study. Among 97,275 eligible women in the California
      Teachers Study cohort who completed the baseline dietary assessment in 1995-1996,
      280 women developed invasive or borderline ovarian cancer by December 31, 2003.
      Multivariable Cox proportional hazards regression, with age as the timescale, was
      used to estimate relative risks and 95% confidence intervals; all statistical
      tests were two sided. Intake of isoflavones was associated with lower risk of
      ovarian cancer. Compared with the risk for women who consumed less than 1 mg of
      total isoflavones per day, the relative risk of ovarian cancer associated with
      consumption of more than 3 mg/day was 0.56 (95% confidence interval: 0.33, 0.96).
      Intake of isothiocyanates or foods high in isothiocyanates was not associated
      with ovarian cancer risk, nor was intake of macronutrients, antioxidant vitamins,
      or other micronutrients. Although dietary consumption of isoflavones may be
      associated with decreased ovarian cancer risk, most dietary factors are unlikely
      to play a major role in ovarian cancer development.

PMID- 17210956
TI  - Gait characterisation and classification in horses.
AB  - Although a large number of foot-fall sequences are possible in quadrupeds, few
      sequences are routinely used. The aim of this paper is to characterise, by foot
      fall pattern, the gaits used by horses and develop a novel technique to classify
      symmetric and asymmetric gaits using one common criterion. To achieve this speed
      and relative foot-fall, timings of all four limbs of eight Icelandic horses were
      measured using accelerometers. Linear discriminant analysis (LDA) was performed
      to find criteria that are optimal for discriminating between the different gaits.
      This also allowed us to evaluate whether gaits should be considered a continuum
      or as discrete entities. Foot-fall timings (stance times, swing times, duty
      factors and stride frequencies) for walk, tolt, trot, pace, left canter, right
      canter, left gallop and right gallop during over-ground locomotion at a range of
      speeds are presented. In the gaits of walk, tolt, trot and pace, foot-fall
      timings were equal between left and right hindlimbs and forelimbs so these gaits
      can be considered as symmetrical. Differences in stance times and duty factors
      were observed between gaits but are unlikely to be of biological significance due
      to their similar magnitude and inconsistent relative trends. This implies that
      metabolics or peak limb forces derived from contact times are unlikely to be the
      principal driving factors in gait transition between walk, trot, pace, canters
      and gallops, although these factors may influence the use of tolt at the lower
      and higher speeds. Gaits did cluster in the LDA space and the running gaits
      (tolt, trot, pace, left and right canters and gallops) could be considered a
      kinematic continuum but the relative relationship with walk may be more complex.
      Thus, LDA analysis has enabled common criteria to be discovered to accurately
      classify equine gaits on the basis of foot-fall timings on a stride-by-stride
      basis.

PMID- 17210957
TI  - The desert ant odometer: a stride integrator that accounts for stride length and
      walking speed.
AB  - Desert ants, Cataglyphis, use path integration as a major means of navigation.
      Path integration requires measurement of two parameters, namely, direction and
      distance of travel. Directional information is provided by a celestial compass,
      whereas distance measurement is accomplished by a stride integrator, or
      pedometer. Here we examine the recently demonstrated pedometer function in more
      detail. By manipulating leg lengths in foraging desert ants we could also change
      their stride lengths. Ants with elongated legs ('stilts') or shortened legs
      ('stumps') take larger or shorter strides, respectively, and misgauge travel
      distance. Travel distance is overestimated by experimental animals walking on
      stilts, and underestimated by animals walking on stumps - strongly indicative of
      stride integrator function in distance measurement. High-speed video analysis was
      used to examine the actual changes in stride length, stride frequency and walking
      speed caused by the manipulations of leg length. Unexpectedly, quantitative
      characteristics of walking behaviour remained almost unaffected by imposed
      changes in leg length, demonstrating remarkable robustness of leg coordination
      and walking performance. These data further allowed normalisation of homing
      distances displayed by manipulated animals with regard to scaling and speed
      effects. The predicted changes in homing distance are in quantitative agreement
      with the experimental data, further supporting the pedometer hypothesis.

PMID- 17210958
TI  - Ground forces applied by galloping dogs.
AB  - The gallop differs from most other quadrupedal gaits in that each limb plays a
      unique role. This study compares the ground forces applied by the four limbs and
      uses force differences between limbs to address the question of why the gallop is
      the fastest quadrupedal gait. Individual ground forces were recorded from each of
      the four limbs as six dogs galloped down a runway at constant speed. Trials were
      videotaped at high speed using a camera positioned perpendicular to the runway,
      and velocity was measured using photosensors. The trailing forelimb applied
      greater peak vertical forces than the lead forelimb, however the vertical
      impulses from the two forelimbs were similar because the lead forelimb had a
      longer contact interval. The trailing forelimb and lead hindlimb applied greater
      peak accelerating forces and accelerating force impulses than their contralateral
      limbs despite their tendency to have shorter contact intervals. The accelerating
      impulse of both forelimbs combined did not differ significantly from that of both
      hindlimbs. The forelimbs applied a greater decelerating impulse than the
      hindlimbs, such that their net fore-aft impulse was decelerating whereas that of
      the hindlimbs was accelerating. The greater accelerating impulse applied by the
      trailing forelimb and greater decelerating impulse applied by the lead forelimb
      are consistent with the forelimbs acting as elastic struts rather than being
      actively retracted. In contrast, greater accelerating forces were produced by the
      lead hindlimb while the center of mass was lifted, suggesting that the hindlimbs
      are more actively extended or retracted during stance. The differences in ground
      forces measured between paired limbs suggest that the lead forelimb and trailing
      hindlimb are limited in their ability to apply forces by their positions in the
      stride cycle rather than by their muscular capacity. Although a bound or half
      bound would allow more limbs to produce their maximal forces, a gallop may
      generate higher speeds because it is more efficient. Galloping could be more
      efficient than other gaits involving sagittal bending if the increased number of
      ground contact intervals decreased either the decelerating forces applied at the
      onset of ground contact or the vertical motion of the center of mass.

PMID- 17210959
TI  - Suppression of water loss during adult diapause in the northern house mosquito,
      Culex pipiens.
AB  - One of the major challenges of overwintering in the mosquito, Culex pipiens, is
      prevention of dehydration. In this study, we compare the water balance
      requirements of nondiapausing and diapausing adult females of C. pipiens.
      Although their percentage water content is lower, diapausing females contain both
      higher initial and dry masses than nondiapausing individuals. Both nondiapausing
      and diapausing females tolerate a loss of up to 40% of their water mass before
      dying, but diapausing female C. pipiens reach this point after a longer period
      due to their lower rate of water loss. Males, which do not overwinter in
      diapause, showed no differences in their water balance characteristics when
      reared under diapausing or nondiapausing conditions. Likewise, no changes were
      noted in the water balance of pupae, indicating that diapause-related changes do
      not occur prior to adult eclosion. This mosquito does not replenish internal
      water stores by generating metabolic water or by absorbing vapor from the
      atmosphere, but instead relies on drinking liquid water (or blood feeding in the
      case of nondiapausing females). The critical transition temperature, a point
      where water loss increases rapidly with temperature, was the highest for females,
      then males, then pupae, but was not influenced by the diapause program. Females
      in diapause did not utilize common polyols (glycerol, trehalose and sorbitol) to
      retain water, but instead the presence of twice the amount of cuticular
      hydrocarbons in diapausing compared with nondiapausing females suggests that the
      deposition of hydrocarbons contribute to the reduced rates of water loss. The
      laboratory results were also verified in field-collected specimens: mosquitoes in
      the late fall and winter had a lower percentage water content and water loss
      rate, higher initial mass, dry mass and more cuticular hydrocarbons than
      individuals collected during the summer. Thus, the major features of diapause
      that contribute to the suppression of water loss are the large size of diapausing
      females (reduction of surface area to volume ratio lowers cuticular water loss),
      their low metabolic rate and the deposition of extra cuticular hydrocarbons.

PMID- 17210960
TI  - Afferent input modulates the chronic hypercapnia-induced increase in respiratory
      related central pH/CO2 chemosensitivity in the cane toad (Bufo marinus).
AB  - The goal of this study was to examine the role of respiratory-related afferent
      input on the chronic hypercapnia (CHC)-induced increase in central respiratory
      related pH/CO2 chemosensitivity in cane toads (Bufo marinus). Toads were exposed
      to CHC (3.5% CO2) for 10 days, following which in vitro brainstem-spinal cord
      preparations were used to assess central respiratory-related pH/CO2
      chemosensitivity. Motor output from the vagus nerve root was used as an index of
      breathing (fictive breathing). Olfactory denervation (OD), prior to exposure to
      CHC, was used to remove the influence of CO2-sensitive olfactory chemoreceptors,
      which inhibit breathing. Exposure to chronic hyperoxic hypercapnia (CHH) was used
      to reduce the level of arterial chemoreceptor input compared with CHC alone. In
      vivo experiments examined the effects of CHC, CHH and OD on the acute hypercapnic
      ventilatory response of intact animals. In vitro, a reduction in artifical
      cerebral spinal fluid (aCSF) pH increased fictive breathing in preparations taken
      from control and CHC animals. CHC caused an increase in fictive breathing
      compared with controls. OD and CHH abolished the CHC-induced augmentation of
      fictive breathing. In vivo, CHC did not cause an augmentation of the acute
      hypercapnic ventilatory response. CHH reduced the in vivo acute hypercapnic
      ventilatory response compared with animals exposed to CHC. In vivo, OD reduced
      breathing frequency and increased breath amplitude in both control and CHC
      animals. The results suggest that afferent input from olfactory and arterial
      chemoreceptors, during CHC, is involved in triggering the CHC-induced increase in
      central respiratory-related pH/CO2 chemosensitivity.

PMID- 17210961
TI  - The kinematics of multifunctionality: comparisons of biting and swallowing in
      Aplysia californica.
AB  - What are the mechanisms of multifunctionality, i.e. the use of the same
      peripheral structures for multiple behaviors? We studied this question using the
      multifunctional feeding apparatus of the marine mollusk Aplysia californica, in
      which the same muscles mediate biting (an attempt to grasp food) and swallowing
      (ingestion of food). Biting and swallowing responses were compared using magnetic
      resonance imaging of intact, behaving animals and a three-dimensional kinematic
      model. Biting is associated with larger amplitude protractions of the grasper
      (radula/odontophore) than swallowing, and smaller retractions. Larger biting
      protractions than in swallowing appear to be due to a more anterior position of
      the grasper as the behavior begins, a larger amplitude contraction of protractor
      muscle I2, and contraction of the posterior portion of the I1/I3/jaw complex. The
      posterior I1/I3/jaw complex may be context-dependent, i.e. its mechanical context
      changes the direction of the force it exerts. Thus, the posterior of I1/I3 may
      aid protraction near the peak of biting, whereas the entire I1/I3/jaw complex
      acts as a retractor during swallowing. In addition, larger amplitude closure of
      the grasper during swallowing allows an animal to exert more force as it ingests
      food. These results demonstrate that differential deployment of the periphery can
      mediate multifunctionality.

PMID- 17210962
TI  - Growing out of a caste--reproduction and the making of the queen mole-rat.
AB  - Naked mole-rats have a eusocial colony structure consisting of non-reproductive
      workers and a reproductively active caste where a single, dominant queen and 1-3
      males produce all of the offspring. Well-established queens have elongated bodies
      that characterize their caste. Worker females retain the ability to transform
      into queens, however the trigger and time course for this physical transformation
      remain a mystery. Here, we show a direct link between periods of pregnancy and
      vertebral lengthening in nascent queens. Adult female mole-rats were paired with
      a male and radiographed weekly for two and a half years to track the growth of
      the lumbar vertebrae as the mole-rats became sexually mature and experienced
      pregnancies. The lumbar vertebrae of breeding females grew at an increased rate
      during each pregnancy but growth rates returned to normal between pregnancies and
      during extended periods without reproduction. The rate of lumbar lengthening was
      reduced to normal rates in older, established queens experiencing pregnancies.
      Our results imply that the length of a new queen mole-rat is proportional to the
      number of pregnancies experienced and suggest that hormones related to pregnancy
      may play the critical role in bone growth associated with caste transformation.

PMID- 17210963
TI  - Parameters of variable reward distributions that affect risk sensitivity of honey
      bees.
AB  - We investigated risk sensitivity with harnessed honey bees in a proboscis
      extension conditioning paradigm. We conditioned each subject to turn its head and
      extend its proboscis towards one of two presented odors; one odor was associated
      with a constant reward and the other with a variable reward that was either low
      or high, with probabilities P and (1-P), respectively. Reward values and
      probabilities were set so that the expected value of the variable alternative was
      equal to that of the constant one. We performed six experimental conditions in
      which variability was in reward volume and three conditions in which variability
      was in reward concentration. The experiments were designed to systematically test
      the effect of various parameters that describe the reward distributions on levels
      of risk sensitivity. Risk aversion was greatest when variability was in reward
      volume, and the variable distribution included zero rewards and had a high
      coefficient of variation (CV=s.d./mean). The variance itself did not affect risk
      sensitivity. Subjects were risk indifferent when the variable distribution did
      not include zero rewards, however these distributions were positively skewed. The
      independent effects of zero rewards and distribution skew remain to be tested.
      Subjects were risk indifferent in conditions where variability was in reward
      concentration, but concentration range was limited and these distributions did
      not include zero rewards and were skewed. We conclude that risk aversion to
      variability in reward amount is a robust phenomenon for some reward
      distributions. A systematic evaluation of the effect of various reward
      distribution parameters on choice behavior should complement functional and
      mechanistic approaches.

PMID- 17210964
TI  - Total body oxygen stores and physiological diving capacity of California sea
      lions as a function of sex and age.
AB  - A defining physiological capability for air-breathing marine vertebrates is the
      amount of oxygen that can be stored in tissues and made available during dives.
      To evaluate the influence of oxygen storage capacity on aerobic diving capacity,
      we examined the extent to which blood and muscle oxygen stores varied as a
      function of age, body size and sex in the sexually dimorphic California sea lion,
      Zalophus californianus. We measured total body oxygen stores, including
      hematocrit, hemoglobin, MCHC, plasma volume, blood volume and muscle myoglobin in
      pups through adults of both sexes. Blood and muscle oxygen storage capacity was
      not fully developed by the end of the dependency period, with blood stores not
      fully developed until animals were larger juveniles (70 kg; 1.5-2.5 years) and
      muscle stores not until animals were sub-adult size (125 kg; 4-6 years).
      Differences in aerobic diving capacity among size classes were reflective of
      these major milestones in the development of oxygen stores. Male sea lions had
      greater absolute blood volume than females and reflected the larger mass of
      males, which became apparent when animals were large juveniles. Adult female sea
      lions had greater muscle myoglobin concentrations compared to males, resulting in
      greater mass-specific muscle and total oxygen stores. Delayed development of
      oxygen stores is consistent with the shallow epi-mesopelagic foraging behavior in
      this species. We hypothesize that the greater mass-specific oxygen stores of
      female sea lions compared to males is related to differences in foraging behavior
      between the sexes.

PMID- 17210965
TI  - The energetic consequence of specific dynamic action in southern bluefin tuna
      Thunnus maccoyii.
AB  - The effect of feeding on the rate of oxygen consumption (M(O2)) of four groups of
      three southern bluefin tuna Thunnus maccoyii (SBT) was examined in a large static
      respirometer at water temperatures of 18.2-20.3 degrees C. Six feeding events of
      rations between 2.1-8.5% body mass (%M(b)) of Australian sardines (Sardinops
      neopilchardus) were recorded (two of the groups were fed twice). Before feeding,
      fish swam between 0.71 and 1.4 body lengths s(-1) (BL s(-1)) and the routine
      metabolic rate (RMR) was 366+/-32.5 mg kg(-1) h(-1) (mean +/- s.e.m.). For all
      trials, M(O2) was elevated post feeding, presumably as a result of specific
      dynamic action (SDA). Swimming velocity was also elevated post feeding for
      periods similar to that of M(O2) (between 20-45 h, longest for the largest
      rations). Post feeding swimming velocity increased to between 0.87-2.6 BL s(-1)
      and was also dependent on ration consumed. It is suggested that the purpose of
      increased post-feeding swimming velocity was to increase ventilation volume as a
      response to the enhanced metabolic demand associated with SDA. Peak post-prandial
      M(O2) increased linearly with ration size to a maximum of 1290 mg kg(-1) h(-1),
      corresponding to 2.8 times the RMR. When converted to its energy equivalent,
      total magnitude of SDA was linearly correlated with ration size to a maximum of
      192 kJ kg(-1) h(-1), and as a proportion of gross energy ingested (SDA
      coefficient), it averaged 35+/-2.2%. These results demonstrate that, although the
      factorial increase of SDA in SBT is similar to that of other fish species, the
      absolute energetic cost of SDA is much higher. These results support the
      contention that tuna are energy speculators, gambling high rates of energy
      expenditure for potentially higher rates of energy returns. The ration that
      southern bluefin tuna require to equal the combined metabolic costs of SDA and
      RMR is estimated in this study to be 3.5%M(b) of Australian sardines per day.

PMID- 17210966
TI  - Quantitative analysis of tethered and free-swimming copepodid flow fields.
AB  - We quantified the flow field generated by tethered and free-swimming Euchaeta
      antarctica using the particle image velocimetry (PIV) technique. The streamlines
      around the free-swimming specimens were generally parallel to the body axis,
      whereas the streamlines around all of the tethered copepodids demonstrated
      increased curvature. Differences noted in the streamline pattern, and hence the
      vorticity, dissipation rate and strain rate fields, are explained by considering
      the forces on the free-swimming specimen compared to the tethered specimen.
      Viscous flow theory demonstrates that the force on the fluid due to the presence
      of the tether irrevocably modifies the flow field in a manner that is consistent
      with the measurements. Hence, analysis of the flow field and all associated
      calculations differ for tethered versus free-swimming conditions. Consideration
      of the flow field of the free-swimming predatory copepodid shows the intensity of
      the biologically generated flow and the extent of the mechanoreceptive signal
      quantified in terms of shear strain rate. The area in the dorso-ventral view
      surrounded by the 0.5 s(-1) contour of e(xy), which is a likely threshold to
      induce an escape response, is 11 times the area of the exoskeletal form for the
      free-swimming case. Thus, mechanoreceptive predators will perceive a more
      spatially extended signal than the body size.

PMID- 17210967
TI  - The predictive start of hunting archer fish: a flexible and precise motor pattern
      performed with the kinematics of an escape C-start.
AB  - Once their shots have successfully dislodged aerial prey, hunting archer fish
      monitor the initial values of their prey's ballistic motion and elicit an adapted
      rapid turning maneuver. This allows these fish to head straight towards the later
      point of catch with a speed matched to the distance to be covered. To make the
      catch despite severe competition the fish must quickly and yet precisely match
      their turn and take-off speed to the initial values of prey motion. However, the
      initial variables vary over broad ranges and can be determined only after prey is
      dislodged. Therefore, the underlying neuronal circuitry must be able to drive a
      maneuver that combines a high degree of precision and flexibility at top speed.
      To narrow down which neuronal substrate underlies the performance we
      characterized the kinematics of archer fish predictive starts using digital high
      speed video. Strikingly, the predictive starts show all hallmarks of Mauthner
      driven teleost C-type fast-starts, which have previously not been noted in
      feeding strikes and were not expected to provide the high angular accuracy
      required. The high demands on flexibility and precision of the predictive starts
      do not compromise their performance. On the contrary, archer fish predictive
      starts are among the fastest C-starts known so far among teleost fish, with peak
      linear speed beyond 20 body lengths s(-1), angular speed over 4500 deg. s(-1),
      maximum linear acceleration of up to 12 times gravitational acceleration and peak
      angular acceleration of more than 450 000 deg. s(-2). Moreover, they were not
      slower than archer fish escape C-starts, elicited in the same individuals.
      Rather, both escapes and predictive starts follow an identical temporal pattern
      and all kinematic variables of the two patterns overlap. This kinematic
      equivalence strongly suggests that archer fish recruit their C-start escape
      network of identified reticulospinal neurons, or elements of it, to drive their
      predictive starts. How the network drives such a rather complex behavior without
      compromising speed is a wide open question.

PMID- 17210968
TI  - Hydrodynamic function of dorsal and anal fins in brook trout (Salvelinus
      fontinalis).
AB  - Recent kinematic and hydrodynamic studies on fish median fins have shown that
      dorsal fins actively produce jets with large lateral forces. Because of the
      location of dorsal fins above the fish's rolling axis, these lateral forces, if
      unchecked, would cause fish to roll. In this paper we examine the hydrodynamics
      of trout anal fin function and hypothesize that anal fins, located below the
      fish's rolling axis, produce similar jets to the dorsal fin and help balance
      rolling torques during swimming. We simultaneously quantify the wake generated by
      dorsal and anal fins in brook trout by swimming fish in two horizontal light
      sheets filmed by two synchronized high speed cameras during steady swimming and
      manoeuvring. Six major conclusions emerge from these experiments. First, anal
      fins produce lateral jets to the same side as dorsal fins, confirming the
      hypothesis that anal fins produce fluid jets that balance those produced by
      dorsal fins. Second, in contrast to previous work on sunfish, neither dorsal nor
      anal fins produce significant thrust during steady swimming; flow leaves the
      dorsal and anal fins in the form of a shear layer that rolls up into vortices
      similar to those seen in steady swimming of eels. Third, dorsal and anal fin
      lateral jets are more coincident in time than would be predicted from simple
      kinematic expectations; shape, heave and pitch differences between fins, and
      incident flow conditions may account for the differences in timing of jet
      shedding. Fourth, relative force and torque magnitudes of the anal fin are larger
      than those of the dorsal fin; force differences may be due primarily to a larger
      span and a more squarely shaped trailing edge of the anal fin compared to the
      dorsal fin; torque differences are also strongly influenced by the location of
      each fin relative to the fish's centre of mass. Fifth, flow is actively modified
      by dorsal and anal fins resulting in complex flow patterns surrounding the caudal
      fin. The caudal fin does not encounter free-stream flow, but rather moves through
      incident flow greatly altered by the action of dorsal and anal fins. Sixth, trout
      anal fin function differs from dorsal fin function; although dorsal and anal fins
      appear to cooperate functionally, there are complex interactions between other
      fins and free stream perturbations that require independent dorsal and anal fin
      motion and torque production to maintain control of body position.

PMID- 17210969
TI  - Adaptive regulation of digestive performance in the genus Python.
AB  - The adaptive interplay between feeding habits and digestive physiology is
      demonstrated by the Burmese python, which in response to feeding infrequently has
      evolved the capacity to widely regulate gastrointestinal performance with feeding
      and fasting. To explore the generality of this physiological trait among pythons,
      we compared the postprandial responses of metabolism and both intestinal
      morphology and function among five members of the genus Python: P. brongersmai,
      P. molurus, P. regius, P. reticulatus and P. sebae. These infrequently feeding
      pythons inhabit Africa, southeast Asia and Indonesia and vary in body shape from
      short and stout (P. brongersmai) to long and slender (P. reticulatus). Following
      the consumption of rodent meals equaling 25% of snake body mass, metabolic rates
      of pythons peaked at 1.5 days at levels 9.9- to 14.5-fold of standard metabolic
      rates before returning to prefeeding rates by day 6-8. Specific dynamic action of
      these meals (317-347 kJ) did not differ among species and equaled 23-27% of the
      ingested energy. For each species, feeding triggered significant upregulation of
      intestinal nutrient transport and aminopeptidase-N activity. Concurrently,
      intestinal mass doubled on average for the five species, in part due to an 85%
      increase in mucosal thickness, itself a product of 27-59% increases in enterocyte
      volume. The integrative response of intestinal functional upregulation and tissue
      hypertrophy enables each of these five python species, regardless of body shape,
      to modulate intestinal performance to meet the demands of their large infrequent
      meals.

PMID- 17210970
TI  - Genetic dissection of attractant-induced conductances in Paramecium.
AB  - Paramecium tetraurelia is attracted to acetate and biotin by swimming smoothly
      and fast up gradients of these attractants, and turning immediately and slowing
      down when leaving these stimuli. We use a group of mutants, each with a different
      defect in an identified ion conductance, to show that these two stimuli open
      different ion channels, and the behaviors that occur upon application of stimulus
      (on-response) and removal of stimulus (off-response) have different roles in
      attraction to these two stimuli. The most important parameters for successful
      attraction to acetate are the on-response behaviors of fast swimming with few
      turns, and the mutants' behavior suggests that I(K(Ca,h)) is the conductance
      involved that initiates this behavior. I(K(Ca,h or d)) appears to be important to
      the on-response in biotin; the results with mutants suggest that the biotin off
      response depolarization is initiated by an I(Ca), which can be large enough or
      close enough to channels to open I(K(Ca,d)), I(Na(Ca)) and I(Mg(Ca)).

PMID- 17210971
TI  - Experimental study of coordination patterns during unsteady locomotion in
      mammals.
AB  - A framework to study interlimb coordination, which allowed the analysis of all
      the symmetrical and asymmetrical gaits, was recently proposed. It suggests that
      gait depends on a common basic pattern controlling the coordination of the
      forelimbs (fore lag, FL), the coordination of the hindlimbs (hind lag, HL) and
      the relationship between these two pairs of limbs (pair lag, PL) in an
      anteroposterior sequence of movement (APS). These three time parameters are
      sufficient for identifying all steady gaits. We assumed in this work that this
      same framework could also be used to study non-steady locomotion, particularly
      the transitions between symmetrical and asymmetrical gaits. Moreover, as the
      limbs are coordinated in time and also in space during locomotion, we associated
      three analogous space parameters (fore gap, FG; hind gap, HG and pair gap, PG) to
      the three time parameters. We studied the interlimb coordination of dogs and cats
      moving on a runway with a symmetrical gait. In the middle of the runway, the gait
      was disturbed by an obstacle, and the animal had to change to an asymmetrical
      coordination to get over it. The time (FL, HL, PL) and space (FG, HG, PG)
      parameters of each sequence of the trials were calculated. The results
      demonstrated that the APS method allows quantification of the interlimb
      coordination during the symmetrical and asymmetrical phases and during the
      transition between them, in both dogs and cats. The space and time parameters
      make it possible to link the timing and the spacing of the footfalls, and to
      quantify the spatiotemporal dimension of gaits in different mammals. The slight
      differences observed between dogs and cats could reflect their morphological
      differences. The APS method could thus be used to understand the implication of
      morphology in interlimb coordination. All these results are consistent with
      current knowledge in biomechanics and neurobiology, therefore the APS reflects
      the actual biological functioning of quadrupedal interlimb coordination.

PMID- 17210972
TI  - Differential diagnosis of Parkinson's disease: a new blood test?

PMID- 17210973
TI  - Cytokines in uveitis.

PMID- 17210975
TI  - Assessment of female participation in an employee 20-week walking incentive
      program at Marshfield Clinic: a large multispecialty group practice.
AB  - OBJECTIVE: We evaluated the short-term effect of a worksite-based walking
      incentive program to promote physical activity and well-being in employees of a
      private healthcare clinic. DESIGN: A prospective, observational follow-up study.
      SETTING: The study was conducted at Marshfield Clinic, a large private
      multispecialty group practice healthcare institution in Marshfield,Wisconsin,
      USA. PATIENTS: Subjects for this study were Marshfield Clinic physicians and
      staff. METHODS: From March 31, 2005 to August 20, 2005, physical activity level,
      body mass index (BMI) and other well-being characteristics were observed pre- and
      post-program among 191 female participants from the Marshfield Clinic. A brief
      Web site-accessible, self-reported survey assessed the effectiveness of the
      exercise program. RESULTS: Our data show a statistically significant (p <0.0001)
      increase in participants' physical activity level, while a significant (p =
      0.021) decrease in mean BMI was observed. However, there was no evidence of our
      incentive program reducing participants' blood pressure. CONCLUSION: Preliminary
      findings of our study suggest that the goal of worksite programs designed to
      support employees in their efforts to improve or maintain their level of wellness
      is potentially achievable. Continuing research is needed to further assess
      whether persistent health benefits can be induced by worksite wellness programs.

PMID- 17210974
TI  - Innate immunity SNPs are associated with risk for severe sepsis after burn
      injury.
AB  - OBJECTIVE: To analyze allelic association with clinical outcome in a cohort of
      burn patients. PATIENTS: Two hundred twenty-eight individuals with burns > or
      =15% total body surface area without significant non-burn related trauma who
      survived >48 hours post-admission were enrolled. One hundred fifty-nine of these
      patients were analyzed previously. METHODS: Candidate polymorphisms within
      interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor alpha
      (TNF-alpha), cellular differentiation marker 14 (CD14) and toll-like receptor 4
      (TLR4) were evaluated by logistic regression analysis for association with
      increased risk for severe sepsis (sepsis plus organ dysfunction or shock).
      RESULTS: After adjustment for age, burn size, ethnicity, gender and inhalation
      injury, alleles at TNF-alpha (308G, p=0.013), TLR4 (+896G, p=0.027), IL-6 (174C,
      p=0.040) and CD14 (159C, p=0.047) were significantly associated with an increased
      risk for severe sepsis. CONCLUSIONS: Carriage of variant alleles at immune
      response genes were associated with increased risk for severe sepsis after burn
      injury.

PMID- 17210976
TI  - Comparison of an in-house and a commercial RD1-based ELISPOT-IFN-gamma assay for
      the diagnosis of Mycobacterium tuberculosis infection.
AB  - OBJECTIVE: To compare a RD1-based in-house ELISPOT-interferon-gamma (IFN-gamma)
      assay with a commercial (T-SPOT.TB) assay for the diagnosis of Mycobacterium
      tuberculosis (TB) infection and the efficacy of the tuberculin skin test (TST)
      and ELISPOT assay in detecting latent TB infection (LTBI). DESIGN: Eighty-six
      subjects (65 household contacts of contagious TB-infected patients, 13 subjects
      with active or previous TB infection, and 8 with suspected TB infection) were
      consecutively recruited in the context of a surveillance program. METHODS:
      Enrolled subjects underwent the Mantoux TST and two different ELISPOT-IFN-gamma
      assays: an in-house assay using a pool of selected M. tuberculosis peptides (MTP)
      and the commercial T-SPOT.TB assay. RESULTS: The in-house and commercial ELISPOT
      IFN-gamma assays showed almost complete concordance (99%) in diagnosing acute or
      LTBI. When comparing the efficacy of the TST with the in-house ELISPOT assay in
      detecting TB infection, a small agreement was observed (k=0.344, P<0.0001): 36%
      of the subjects with a positive TST were ELISPOT-MTP negative and 12% with a
      negative TST were ELISPOT-MTP positive. Furthermore, 78% of the ELISPOT-MTP
      negative individuals were ELISPOT- Bacillus Calmette-Guerin (BCG) positive, most
      of whom had received BCG vaccination. CONCLUSION: Our in-house ELISPOT assay
      based on a restricted pool of highly selected peptides is equivalent to the
      commercial T-SPOT.TB assay, is cheaper and is probably not confounded, unlike the
      TST, by BCG vaccination in our setting.

PMID- 17210979
TI  - Lupus and pregnancy: complex yet manageable.
AB  - Systemic lupus erythematosus is a chronic multi-system autoimmune disease that
      occurs predominantly in women of childbearing age. The risk of complications and
      adverse fetal outcomes in pregnant women with lupus is high. Moreover, pregnancy
      can cause flares of lupus disease activity necessitating maternal
      immunosuppressive intervention. Interestingly, many potential complications of
      pregnancy present as symptoms of lupus making diagnosis and treatment a
      challenge. Advancing technology and better understanding of the maternal-fetal
      dyad in lupus have improved outcomes in lupus pregnancies over the last 40 years.
      This article will briefly review the important issues in pregnancies complicated
      by lupus and provide a general guideline to physicians for monitoring and
      treatment.

PMID- 17210978
TI  - Cytokines and chemokines in uveitis: is there a correlation with clinical
      phenotype?
AB  - Uveitis is a general term for intraocular inflammation and includes a large
      number of clinical phenotypes. As a group of disorders, it is responsible for 10%
      of all registered blind patients under the age of 65 years. Immune-mediated
      uveitis may be associated with a systemic disease or may be localized to the eye.
      The pro-inflammatory cytokines interleukin (IL)-1beta, IL-2, IL-6, interferon
      gamma and tumor necrosis factor-alpha have all been detected within the ocular
      fluids or tissues in the inflamed eye together with others, such as IL-4, IL-5,
      IL-10 and transforming growth factor-beta. The chemokines IL-8, monocyte
      chemoattractant protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP
      1beta and fractalkine are also thought to be involved in the associated
      inflammatory response. There have been a number of studies in recent years
      investigating cytokine profiles in different forms of uveitis with a view to
      determining what cytokines are important in the inflamed eye. This review
      attempts to present the current state of knowledge from in vitro and in vivo
      research on the inflammatory cytokines in intraocular inflammatory diseases.

PMID- 17210980
TI  - Growth hormone stimulation tests in the differential diagnosis of Parkinson's
      disease.
AB  - Idiopathic Parkinson's disease (IPD) is a common neurodegenerative disorder whose
      differential diagnosis from other forms of atypical parkinsonism, for instance
      multiple system atrophy (MSA) or progressive supranuclear palsy, may be
      difficult, especially in the early stages. Growth hormone stimulation tests have
      been recently reported to be useful in the differential diagnosis between IPD and
      MSA. Both clonidine, an alpha(2)-adrenoceptor agonist, and arginine, an amino
      acid activating the cholinergic system, have been used to assess growth hormone
      response in patients with IPD and MSA. This review summarizes the results of
      several studies and discusses the validity of these tests in the differential
      diagnosis of parkinsonisms.

PMID- 17210982
TI  - Asymptomatic hepatomegaly with elevated serum transaminases: diagnosis?

PMID- 17210977
TI  - An armamentarium of wart treatments.
AB  - Patients and clinicians experience the frustration of cutaneous viral warts
      caused by infection with the human papilloma virus (HPV).Warts appear in various
      forms on different sites of the body and include common warts (verruca vulgaris),
      plane or flat warts, myrmecia, plantar warts, coalesced mosaic warts, filiform
      warts, periungual warts, anogenital warts (venereal or condyloma acuminata), oral
      warts and respiratory papillomas. Cervical infection with HPV is now known to
      cause cervical cancer if untreated. A review of the medical literature reveals a
      huge armamentarium of wart monotherapies and combination therapies. Official
      evidence-based guidelines exist for the treatment of warts, but very few of the
      reported treatments have been tested by rigorous blinded, randomized controlled
      trials.Therefore, official recommendations do not often include treatments with
      reportedly high success rates, but they should not be ignored when considering
      treatment options. It is the purpose of this review to provide a comprehensive
      overview of the wart treatment literature to expand awareness of the options
      available to practitioners faced with patients presenting with problematic warts.

PMID- 17210981
TI  - Determinants of early life leptin levels and later life degenerative outcomes.
AB  - The early (intrauterine and neonatal) life environment plays an important role in
      programming the susceptibility in later life to chronic degenerative diseases,
      such as obesity, cardiovascular diseases, diabetes mellitus, cancer and
      osteoporosis. Among other hormones, leptin plays a major role in the regulation
      of the overall metabolism and has multiple neuroendocrine (adeno- and neuro
      hypophysis axes and the hypothalamus-pituitary-adrenal axis) and immune
      functions. The hormone exerts its actions beginning in the early life time
      period, regulating the intrauterine and early extrauterine life growth and
      development, as well as the adaptation to extrauterine life, neonatal
      thermogenesis and response to stress. Recent findings also support a role of
      leptin in the process of fetal bone remodeling and brain development. Therefore,
      it is of interest to explore the physiology of leptin in early life, as well as
      those factors that may perturb the balance of the hormone with pathological
      consequences in terms of confining an increased risk for disease in later life.
      This review aims to summarize reported findings concerning the role of leptin in
      early life, as well as the association of fetal, maternal and placental factors
      with leptin levels, while attempting to speculate mechanisms through which these
      factors may influence the risk for developing chronic diseases in later life.

PMID- 17210983
TI  - Managing dyspepsia in a primary care setting.

PMID- 17210984
TI  - Lipidomics reveals that adiposomes store ether lipids and mediate phospholipid
      traffic.
AB  - Lipid droplets are accumulations of neutral lipids surrounded by a monolayer of
      phospholipids and associated proteins. Recent proteomic analysis of isolated
      droplets suggests that they are part of a dynamic organelle system that is
      involved in membrane traffic as well as packaging and distributing lipids in the
      cell. To gain a better insight into the function of droplets, we used a
      combination of mass spectrometry and NMR spectroscopy to characterize the lipid
      composition of this compartment. In addition to cholesteryl esters and
      triacylglycerols with mixed fatty acid composition, we found that approximately
      10-20% of the neutral lipids were the ether lipid monoalk(en)yl diacylglycerol.
      Although lipid droplets contain only 1-2% phospholipids by weight, >160 molecular
      species were identified and quantified. Phosphatidylcholine (PC) was the most
      abundant class, followed by phosphatidylethanolamine (PE), phosphatidylinositol,
      and ether-linked phosphatidylcholine (ePC). Relative to total membrane, droplet
      phospholipids were enriched in lysoPE, lysoPC, and PC but deficient in
      sphingomyelin, phosphatidylserine, and phosphatidic acid. These results suggest
      that droplets play a central role in ether lipid metabolism and intracellular
      lipid traffic.

PMID- 17210985
TI  - Development and characterization of a novel anti-ceramide antibody.
AB  - Ceramide is emerging as a key sphingolipid that regulates a variety of cellular
      processes. To facilitate the study of ceramide localization and its interaction
      with cellular proteins, we have developed a novel antibody against ceramide. Our
      results indicate that the antibody (rabbit IgG) specifically recognizes ceramide
      in lipid overlay assays and detects ceramide species with different fatty acid
      chain lengths that include C2, C8, C16, C18, C20, and C24. The new antibody was
      compared with the commercially available anti-ceramide antibody (mouse IgM) in
      immunocytochemistry experiments to study the localization of ceramide. Although
      both antibodies stain the same regions on the cell membrane, the rabbit IgG
      reveals the distribution of ceramide in compartments that are not well identified
      with the commercially available antibody. In addition to staining of ceramide in
      protrusions of the plasma membrane, the rabbit IgG also detects ceramide in the
      Golgi apparatus. Pharmacological depletion or increase of ceramide levels results
      in a corresponding change in staining intensity, confirming the specificity of
      the antibody. These results indicate that the rabbit IgG is a suitable antibody
      to determine the localization of ceramide and its interaction with proteins by
      immunocytochemistry.

PMID- 17210986
TI  - North-South exchange and professional development: experience from Mali and
      France.
AB  - BACKGROUND: Developing countries are facing the challenge of developing a family
      practice culture in a context in which clinical practice remains strongly
      associated with hospital practice. To what extent can professional exchange
      between GPs from North and South fuel novel professional identities in family
      practice? OBJECTIVES: Assess to what extent a North-South professional exchange
      programme involving rural GPs from Mali and France affected practice development
      and professional identity formation of Malian GPs. METHODS: Qualitative analysis
      of 19 exchanges between rural GPs from Mali and France based on (i) interviews;
      (ii) retrospective report analysis; (iii) field observation of three exchanges;
      (iv) workshop with Malian GPs; and (v) workshop with French GPs. RESULTS: Malian
      GPs reported increased self-esteem, increased concern for doctor-patient
      communication and innovations in practice organization. Although Malian
      participants considered a transfer from France's general practice irrelevant, the
      experience was thought provoking. The interpersonal and professional interaction
      was crucial. The Malian Rural Doctors Association provided a platform to
      capitalize on individual experiences in a process of collective professional
      identity construction. Costs of the programme were kept low, limiting possible
      side expectations of participants. CONCLUSIONS: North-South professional exchange
      can contribute to professional development. Exchange programmes should be
      designed as mutual learning processes, rather than unilateral assistance or
      transfer of practice models. Southern family practitioners are likely to improve
      primary care to individuals and families, while Northern GPs can draw lessons
      from the community perspective of primary health care in the South. Recruitment
      and preparation of participants are crucial, as well as collective reflection
      upon return.

PMID- 17210987
TI  - Predicting the likelihood of emergency admission to hospital of older people:
      development and validation of the Emergency Admission Risk Likelihood Index
      (EARLI).
AB  - OBJECTIVE: To develop and evaluate an evidence-based tool for predicting the
      likelihood of emergency admission to hospital of older people aged 75 years and
      over in the UK. METHODS: Prospective cohort study of older people registered with
      17 general practices within Halton Primary Care Trust in the north-west of
      England. A questionnaire with 20 items was sent to older people aged>or=75 years.
      Items for inclusion in the questionnaire were selected from information gleaned
      from published literature and a pilot study. The primary outcome measurement was
      an emergency admission to hospital within 12 months of completing the
      questionnaire. A logistic regression analysis was carried out to identify those
      items which predicted emergency admission to hospital. A scoring system was
      devised to identify those at low, moderate, high and very high risk of admission,
      using the items identified in the predictive modelling process. RESULTS: In
      total, 83% (3032) returned the questionnaire. A simple, six-item tool was
      developed and validated-the Emergency Admission Risk Likelihood Index (EARLI).
      The items included in the tool are as follows: do you have heart problems? [odds
      ratio (OR) 1.40, 95% confidence interval (CI) 1.15-1.72]; do you have leg ulcers?
      (OR 1.46, 95% CI 1.04-2.04); can you go out of the house without help? (OR 0.60,
      95% CI 0.47-0.75); do you have problems with your memory and get confused? (OR
      1.46, 95% CI 1.19-1.81); have you been admitted to hospital as an emergency in
      the last 12 months? (OR 2.16, CI 1.72-2.72); and would you say the general state
      of your health is good? (OR 0.66, 95% CI 0.53-0.82). The tool had high negative
      predictive value (>79%) and identified over 50% of those at high or very high
      risk of emergency admission. A very high score (>20) identified 6% of older
      people, 55% of whom had an emergency admission in the following 12 months. A low
      score (<or=10) identified 74% of the older population of whom 17% were admitted.
      CONCLUSIONS: In this study, we have developed and validated a simple-to-apply
      tool for identifying older people in the UK who are at risk of having an
      emergency admission within the following 12 months. EARLI can be used as a simple
      triage-screening tool to help identify the most vulnerable older people, either
      to target interventions and support to reduce demand on hospital services or for
      inclusion in testing the effectiveness of different preventive interventions.

PMID- 17210989
TI  - Accumulation of ammonium in Norway spruce (Picea abies) seedlings measured by in
      vivo 14N-NMR.
AB  - (14)N-NMR and (31)P-NMR have been used to monitor the in vivo pH in roots, stems,
      and needles from seedlings of Norway spruce, a typical ammonium-tolerant plant.
      The vacuolar and cytoplasmic pH measured by (31)P-NMR was found to be c. pH 4.8
      and 7.0, respectively, with no significant difference between plants growing with
      ammonium or nitrate as the N-source. The (1)H-coupled (14) NH 4+ resonance is pH
      sensitive: at alkaline pH it is a narrow singlet line and below pH 4 it is an
      increasing multiplet line with five signals. The pH values in ammonium-containing
      compartments measured by (14)N-NMR ranged from 3.7 to 3.9, notably lower than the
      estimated pH values of the P(i) pools. This suggests that, in seedlings of Norway
      spruce, ammonium is stored in vacuoles with low pH possibly to protect the
      seedlings against the toxic effects of ammonium ( NH 4+) or ammonia (NH3). It was
      also found that concentrations of malate were 3-6 times higher in stems than in
      roots and needles, with nitrate-grown plants containing more malate than plants
      grown with ammonium.

PMID- 17210988
TI  - Identification of early salt stress response genes in tomato root by suppression
      subtractive hybridization and microarray analysis.
AB  - High salinity is one of the most serious threats to crop production. To
      understand the molecular basis of plant responses to salt stress better,
      suppression subtractive hybridization (SSH) and microarray approaches were
      combined to identify the potential important or novel genes involved in the early
      stage of tomato responses to severe salt stress. First, SSH libraries were
      constructed for the root tissue of two cultivated tomato (Solanum lycopersicum)
      genotypes: LA2711, a salt-tolerant cultivar, and ZS-5, a salt-sensitive cultivar,
      to compare salt treatment and non-treatment plants. Then a subset of clones from
      these SSH libraries were used to construct a tomato cDNA array and microarray
      analysis was carried out to verify the expression changes of this set of clones
      upon a high concentration of salt treatment at various time points compared to
      the corresponding non-treatment controls. A total of 201 non-redundant genes that
      were differentially expressed upon 30 min of severe salt stress either in LA2711
      or ZS-5 were identified from microarray analysis; most of these genes have not
      previously been reported to be associated with salt stress. The diversity of the
      putative functions of these genes indicated that salt stress resulted in a
      complex response in tomato plants.

PMID- 17210990
TI  - Members of the ethylene signalling pathway are regulated in sugarcane during the
      association with nitrogen-fixing endophytic bacteria.
AB  - Nitrogen-fixing bacteria have been isolated from sugarcane in an endophytic and
      beneficial interaction that promotes plant growth. In this work, for the first
      time, the involvement of ethylene signalling in this interaction was investigated
      by molecular characterizing members of this pathway in sugarcane. The expression
      pattern of a putative ethylene receptor (SCER1) and two putative ERF
      transcription factors (SCERF1 and SCERF2) show exclusive modulation in plants
      inoculated with the diazotrophic endophytes. The gene expression profile of
      SCER1, SCERF1, and SCERF2 is differentially regulated in sugarcane genotypes that
      can establish efficient or inefficient associations with diazotrophic micro
      organisms, exhibiting high or low biological nitrogen fixation (BNF) rates,
      respectively. In addition, SCER1, SCERF1, and SCERF2 expression is different in
      response to interactions with pathogenic and beneficial micro-organisms. Taken
      together, that data suggest that SCER1, SCERF1, and SCERF2 might participate in
      specific ethylene signalling cascade(s) that can identify a beneficial endophytic
      association, modulating sugarcane responses toward the diazotrophic endophytes.

PMID- 17210991
TI  - Differential distribution of the lipoxygenase pathway enzymes within potato
      chloroplasts.
AB  - The lipoxygenase pathway is responsible for the production of oxylipins, which
      are important compounds for plant defence responses. Jasmonic acid, the final
      product of the allene oxide synthase/allene oxide cyclase branch of the pathway,
      regulates wound-induced gene expression. In contrast, C6 aliphatic aldehydes
      produced via an alternative branch catalysed by hydroperoxide lyase, are
      themselves toxic to pests and pathogens. Current evidence on the subcellular
      localization of the lipoxygenase pathway is conflicting, and the regulation of
      metabolic channelling between the two branches of the pathway is largely unknown.
      It is shown here that while a 13-lipoxygenase (LOX H3), allene oxide synthase and
      allene oxide cyclase proteins accumulate upon wounding in potato, a second 13
      lipoxygenase (LOX H1) and hydroperoxide lyase are present at constant levels in
      both non-wounded and wounded tissues. Wound-induced accumulation of the jasmonic
      acid biosynthetic enzymes may thus commit the lipoxygenase pathway to jasmonic
      acid production in damaged plants. It is shown that all enzymes of the
      lipoxygenase pathway differentially localize within chloroplasts, and are largely
      found associated to thylakoid membranes. This differential localization is
      consistently observed using confocal microscopy of GFP-tagged proteins,
      chloroplast fractionation, and western blotting, and immunodetection by electron
      microscopy. While LOX H1 and LOX H3 are localized both in stroma and thylakoids,
      both allene oxide synthase and hydroperoxide lyase protein localize almost
      exclusively to thylakoids and are strongly bound to membranes. Allene oxide
      cyclase is weakly associated with the thylakoid membrane and is also detected in
      the stroma. Moreover, allene oxide synthase and hydroperoxide lyase are
      differentially distributed in thylakoids, with hydroperoxide lyase localized
      almost exclusively to the stromal part, thus closely resembling the localization
      pattern of LOX H1. It is suggested that, in addition to their differential
      expression pattern, this segregation underlies the regulation of metabolic fluxes
      through the alternative branches of the lipoxygenase pathway.

PMID- 17210992
TI  - Proteome response of Elymus elongatum to severe water stress and recovery.
AB  - Tall wheatgrass (Elymus elongatum Host) is a drought-tolerant, cool-season forage
      grass native to Iran. A proteomic approach has been applied to identify
      mechanisms of drought responsiveness and tolerance in plants undergoing
      vegetative stage drought stress and then recovery after rewatering. Uniformed
      clones were reproduced from a parent plant collected from Brojen (central region
      of Iran). Clones were grown in pots and drought was initiated by withholding
      water for 16 d. The leaf samples were taken in triplicate from both
      stressed/rewatered plants and continuously watered controls at five times: (i)
      75% FC, (ii) 50% FC, (iii) 25% FC, (iv) 3 d after rewatering, and (v) 14 d after
      rewatering. Changes in the proteome pattern of shoots were studied using two
      dimensional gel electrophoresis. Following the 16 d water stress, both shoot dry
      weight and leaf width decreased up to 67% compared with the well-watered plants,
      whereas proline content increased up to 20-fold. Leaf relative water contents
      (RWC) also declined from 85% to 24%. Out of about 600 protein spots detected on
      any given two-dimensional gel, 58 protein spots were reproducibly and
      significantly changed during drought stress and recovery. Only one protein
      (abscisic acid- and stress-inducible protein) showed significant changes in
      expression and position in response to severe drought. The fifty-eight responsive
      proteins were categorized in six clusters including two groups of proteins
      specifically up- and down-regulated in response to severe drought stress.
      Eighteen proteins belonging to these two groups were analysed by liquid
      chromatography tandem mass spectrometry leading to the identification of 11 of
      them, including the oxygen-evolving enhancer protein 2, abscisic acid- and stress
      inducible protein, several oxidative stress tolerance enzymes, two small heat
      shock proteins, and Rubisco breakdown. The results suggest that E. elongatum may
      tolerate severe drought stress by accumulating proline and several proteins
      related to drought-stress tolerance. Recovery after rewatering might be another
      mechanism by which plants tolerate erratic rainfall in semi-arid regions.

PMID- 17210993
TI  - DNA repair gene polymorphisms and genetic predisposition to cutaneous melanoma.
AB  - The incidence of cutaneous melanoma is rising rapidly in a number of countries.
      The key environmental risk factor is exposure to the ultraviolet (UV) component
      in sunlight. The nucleotide excision repair (NER) pathway deals with the main
      forms of UV-induced DNA damage. We have investigated the hypothesis that
      polymorphisms in NER genes constitute genetic susceptibility factors for
      melanoma. However, not all melanomas arise on sun-exposed sites and so we
      investigated the hypothesis that genes involved in other pathways for the repair
      of oxidative DNA damage may also be involved in susceptibility to melanoma.
      Scotland, with its high incidence of melanoma and stable homogeneous population,
      was ideal for this case-control study, involving 596 Scottish melanoma patients
      and 441 population-based controls. Significant associations were found for the
      NER genes ERCC1 and XPF, with the strongest associations for melanoma cases aged
      50 and under [ERCC1 odds ratio (OR) 1.59, P = 0.008; XPF OR 1.69, P = 0.003].
      Although an XPD haplotype was associated with melanoma, it did not contain the
      variant 751 Gln allele, which has been associated with melanoma in some previous
      studies. No associations were found for the base excision repair and DNA damage
      response genes investigated. An association was also found for a polymorphism in
      the promoter of the vitamin D receptor gene, VDR (OR 1.88, P = 0.005). The
      products of the two NER genes, ERCC1 and XPF, where associations with melanoma
      were found, act together in a rate-limiting step in the repair pathway.

PMID- 17210994
TI  - Breast cancer risk associated with genotypic polymorphism of the mitotic
      checkpoint genes: a multigenic study on cancer susceptibility.
AB  - Aneuploidy occurs early during tumorigenesis and may contribute to tumor
      formation. Tumor cells become aneuploid as a result of aberrant mitotic
      divisions, suggesting a tumorigenic contribution of the mechanisms in maintaining
      chromosomal number stability. We therefore speculated that the genes TTK, MAD2L1,
      BUB1, BUB1B and PTTG1 (Securin), jointly implicated in the regulation of mitotic
      checkpoint, might be associated with breast tumorigenesis. To test this
      hypothesis, this case-control study of 698 primary breast cancer patients and
      1492 healthy controls examined single-nucleotide polymorphisms (SNPs) in these
      mitotic checkpoint genes to define their tumorigenic contribution. Because
      estrogen is known to promote breast cancer development via its mitogenic effect
      leading to malignant proliferation of breast epithelium and the mitotic
      checkpoint genes are involved in regulating mitosis, we were also interested in
      knowing whether any association between genotypes and breast cancer risk was
      modified by reproductive risk factors. Support for these hypotheses came from the
      observations that (i) two SNPs in TTK and PTTG1 were associated with breast
      cancer risk; (ii) haplotype and haplotype combination analyses in TTK, BUB1B and
      PTTG1 revealed a strong association with breast cancer risk; (iii) a trend to an
      increased risk of breast cancer was found in women harboring a greater number of
      putative high-risk genotypes/haplotypes of mitotic checkpoint genes and (iv) a
      significant interaction between high-risk genotypes/haplotypes and reproductive
      risk factors in determining breast cancer risk was defined. This study provides
      new support for the mutator role of mitotic checkpoint genes in breast cancer
      development, suggesting that breast cancer could be driven by genomic instability
      associated with variant mitotic checkpoint genes, the tumorigenic contribution of
      which could be enhanced as a result of increased mitosis due to estrogen
      exposure.

PMID- 17210996
TI  - To life! Reflections on spirituality, palliative practice, and politics.

PMID- 17210997
TI  - Evaluating an end-of-life curriculum in a medical residency program.
AB  - The ability to meet patient needs at the end of life is important. Boston
      University Residency Program in Medicine initiated a 1-week-long end-of-life
      curriculum that included a hospice care orientation, core articles, and home
      hospice visits. Evaluated was the impact of the rotation on participant knowledge
      and attitude. Knowledge was assessed by pretest and posttest questionnaires and
      compared with more senior resident controls, naive to the curriculum. Attitudes
      toward issues relating to end-of-life care and subjective change in knowledge
      were assessed comparing subjects' retrospective preintervention and
      postintervention responses included in the postintervention questionnaire. Forty
      five second-year participants completed both questionnaires. Participants
      demonstrated significant improvements in attitude and self-assessed knowledge of
      end-of-life care in 23 of 24 Likert-type scale questions. The end-of-life
      curriculum led to significant improvements in participant knowledge and attitudes
      about the conceptual and practical aspects of end-of-life care. The structure of
      the rotation should be reproducible in many locales.

PMID- 17210998
TI  - Can family caregivers of terminally ill patients be a reliable source of
      information about the severity of patient symptoms?
AB  - This study examines the reliability of family caregivers' assessments of a
      terminally ill patient's symptoms and identifies patient and caregiver
      characteristics that affect the reliability of caregiver reports. It compares the
      reports of 143 patients in home hospice units with those of their family
      caregiver about patient symptoms during the 3 days preceding the interview
      (Edmonton scale). Correlation coefficients between the patients' and proxies'
      reports were 0.5 to 0.8, indicating moderate-to-high agreement. Characteristics
      that had an independent effect on identical reporting were the patient being
      fully disabled, the care-giver being a woman in good health, the caregiver living
      with the patient, and the caregiver providing assistance with activities of daily
      living and medical care. These results suggest that primary caregivers can be a
      good source of information about a patient's symptoms, although their reports
      should be used with caution.

PMID- 17210999
TI  - Assessing spirituality and religiousness in advanced cancer patients.
AB  - The aim of this study was to translate the Spiritual Involvement and Beliefs
      Scale into the Greek language and validate its psychometric properties in a
      sample of advanced cancer patients treated in a palliative care unit. The scale
      was translated into Greek with the "forward-backward" procedure. It was
      administered twice, with a 3-day interval, to 82 patients with advanced cancer.
      Patients completed the Spiritual Involvement and Beliefs Scale and the Greek
      Hospital Anxiety and Depression Scale. The scale had an overall Cronbach alpha of
      0.89. Overall test-retest reliability was satisfactory at P<.0005. Satisfactory
      construct validity was supported between the Spiritual Involvement and Beliefs
      Scale subscales and Hospital Anxiety and Depression subscales. Interscale and
      interitem correlations were found satisfactory at P<.0005. These results support
      that the Spiritual Involvement and Beliefs Scale is an instrument with
      satisfactory psychometric properties and is a valid research tool for
      spirituality in advanced cancer patients.

PMID- 17211000
TI  - Death anxiety and death competency: the impact of a palliative care volunteer
      training program.
AB  - Before and immediately after the 2 most recent offerings of a local palliative
      care volunteer training program, 17 participants completed the Collett-Lester
      Fear of Death Scale and Bugen's Coping with Death Scale. The training program
      consisted of approximately 27 hours of training presented in 3-hour blocks during
      a 9-week period. Topics included the philosophy and goals of palliative care,
      spiritual issues from a multi-cultural and multifaith perspective, communication,
      the dying process, grief and bereavement, and the role of the volunteer. The
      results showed no differences in participants' pretraining and posttraining
      scores on the 4 subscales of the Fear of Death Scale. However, participants felt
      significantly more able to cope with death and dying after the training program
      than before. With proper training, volunteers will feel more prepared to handle
      situations involving terminal illness and death. In short, they will be more
      effective in their work with dying patients and their families.

PMID- 17211001
TI  - Palliative care in situations of conflict: lessons from Jerusalem.
AB  - Situations of political conflict are characterized by enmity and the potential
      for, or actual, violence. Conflict of this ilk may be manifested as outright war,
      a cycle of terror and reprisals, or a grumbling enmity between religious,
      national, ethnic, or cultural groups. Clinicians delivering palliative care in
      such circumstances confront challenges, including the disruption of
      infrastructure, bias, distrust and enmity, clinician and patient safety, and
      abuse of health care resources by combatants. Providing palliative care despite
      these obstacles is a challenge that requires planning and careful execution. When
      successful, good provision of palliative care, even across lines of conflict, has
      the capacity to mitigate enmity and promote understanding.

PMID- 17211002
TI  - Video-assisted thoracoscopic neurectomy of intercostal nerves in a patient with
      intractable cancer pain.
AB  - Cancer-related pain is complicated and unbearable. Pain management techniques
      must be constantly modified and improved, with the goal of decreasing pain and
      enabling patients to withstand it. A 56-year-old man with colon cancer and
      multiple metastases was suffering from intense pain that was not relieved by
      extremely high doses of intravenous morphine. Temporary pain relief was achieved
      twice by blockade of the intercostal nerves with local anesthetics.
      Radiofrequency ablation was then performed under fluoroscopic monitoring;
      however, the procedure resulted in little pain relief. Finally, a neurectomy to
      cauterize the intercostal nerves was completed with video-assisted thoracoscopy
      under general anesthesia.

PMID- 17211003
TI  - Management of patients with metastatic malignancy in the intensive care unit.
AB  - Intensive care units serve to provide temporary physiologic support to patients
      with reversible organ failure. However, with increasing frequency, patients with
      end-stage and terminal illnesses are being admitted to the intensive care unit.
      Indeed, in the United States, a third of all patients with terminal metastatic
      malignancy are admitted to the intensive care unit, and 60% of all hospital
      deaths occur after such an admission. In many instances, admission to an
      intensive care unit serves only to transform death into a prolonged, painful, and
      undignified process. In patients with a terminal illness, the focus should be on
      measures that ensure comfort, and admission to an intensive care unit should
      generally be avoided. Intensivists, who are charged with making the best use of
      limited resources, should ultimately be the individuals who determine the
      appropriateness of admitting such patients to the intensive care unit.

PMID- 17211004
TI  - The ethics of palliative sedation as a therapy of last resort.
AB  - Many patients nearing the end of life reach a point at which the goals of care
      change from an emphasis on prolonging life and optimizing function to maximizing
      the quality of remaining life, and palliative care becomes a priority. For some
      patients, however, even high-quality aggressive palliative care fails to provide
      relief. For patients suffering from severe pain, dyspnea, vomiting, or other
      symptoms that prove refractory to treatment, there is a consensus that palliative
      sedation is an appropriate intervention of last resort. In this report, the
      National Ethics Committee, Veterans Health Administration examines what is meant
      by palliative sedation, explores ethical concerns about the practice, reviews the
      emerging professional consensus regarding the use of palliative sedation for
      managing severe, refractory symptoms at the end of life, and offers specific
      recommendations for institutional policy.

PMID- 17211006
TI  - The importance of assessing quality of life in patients with neuromuscular
      disorders.

PMID- 17211007
TI  - The first patient who broke my heart.

PMID- 17211010
TI  - Reducing the growing burden of cardiovascular disease in the developing world.
AB  - Cardiovascular disease (CVD) has become the number-one cause of death in the
      developing world. This epidemic has the potential to place a large social and
      economic burden on developing countries, where CVD tends to strike those in their
      prime working years. Since resources for managing CVD are limited, it is
      important that interventions be guided by cost-effectiveness results for low- and
      middle-income countries. Despite the burden, cost-effective strategies exist at
      the population and individual levels for reducing CVD. Integral to all personal
      intervention strategies is an adequate assessment of the underlying risk of
      disease.

PMID- 17211011
TI  - Advances in the prevention and treatment of cardiovascular disease.
AB  - Over the past thirty-five years, U.S. age-adjusted mortality from cardiovascular
      disease declined 50 percent. This marked reduction reflects advances in the
      prevention, diagnosis, and treatment of common cardiovascular conditions.
      Pharmaceutical agents play a major role in prevention of atherosclerosis and its
      consequences: heart attack, stroke, and heart failure. Additionally, novel device
      based therapies contribute to the decline in cardiac morbidity and mortality.
      Whereas innovative strategies based on accurate imaging of the heart and blood
      vessels are implemented widely now, hope exists that lifestyle changes, early
      risk-factor screening, and more efficacious drugs will strikingly reduce
      cardiovascular disease in the future.

PMID- 17211012
TI  - An overview of cardiovascular disease burden in the United States.
AB  - Cardiovascular disease (CVD) is the leading cause of death and a major cause of
      disability worldwide. In the United States, CVD accounted for 34.4 percent of the
      2.4 million deaths in 2003 and remain a major cause of health disparities and
      rising health care costs. In 2006, health care spending and lost productivity
      from CVD exceeded 400 billion dollars. The aging population, obesity epidemic,
      underuse of prevention strategies, and suboptimal control of risk factors could
      exacerbate the future CVD burden. Increased adherence to clinical and community
      level guidelines and renewed emphasis on policy, environmental, and lifestyle
      changes will be crucial for its effective prevention and control.

PMID- 17211013
TI  - The prevention of cardiovascular disease: have we really made progress?
AB  - Despite reductions in cardiovascular disease (CVD) mortality, current evidence
      suggests that CVD is not being prevented but, rather, is being made less lethal.
      Evidence-based guidelines have been developed for secondary, primary, and
      community-based prevention. To improve compliance with secondary prevention
      guidelines, programs must better organize and monitor care. Primary prevention
      requires assessment of risk in asymptomatic people, to yield cost-effective
      benefits. CVD prevention at the societal level should target deleterious behavior
      in community settings, using effective public health interventions. Policy
      options that involve multiple preventive approaches offer the best opportunity to
      minimize the economic and social burdens of CVD.

PMID- 17211015
TI  - Curbing the cardiovascular disease epidemic: aligning industry, government,
      payers, and academics.
AB  - Despite decades of progress in the diagnosis, treatment, and prevention of
      cardiovascular disease, its prevalence continues to grow in both developed and
      developing countries. We have constructed a model, the "cycle of quality," which
      connects the innovation of initial scientific discovery with validated methods of
      translating research into effective delivery. This model can serve as a basis for
      evaluating proposed efforts to improve interactions among private and public
      aspects of health care to accelerate development and appropriate adoption of new
      treatments, and to achieve greater penetration of effective behavioral therapies
      and established technologies, resulting in major improvements in cardiovascular
      health.

PMID- 17211016
TI  - Measuring performance for treating heart attacks and heart failure: the case for
      outcomes measurement.
AB  - To complement the current process measures for treating patients with heart
      attacks and with heart failure, which target gaps in quality but do not capture
      patient outcomes, the Centers for Medicare and Medicaid Services (CMS) has
      proposed the public reporting of hospital-level thirty-day mortality for these
      conditions in 2007. We present the case for including measurements of outcomes in
      the assessment of hospital performance, focusing on the care of patients with
      heart attacks and with heart failure. Recent developments in the methodology and
      standards for outcomes measurement have laid the groundwork for incorporating
      outcomes into performance monitoring efforts for these conditions.

PMID- 17211017
TI  - Evidence, appropriateness, and technology assessment in cardiology: a case study
      of computed tomography.
AB  - As the volume, complexity, and cost of new medical technology increase, the need
      for evaluating benefits and risks becomes increasingly important. Once the formal
      requirements for Food and Drug Administration approval and insurance coverage are
      met, however, few systematic criteria are applied to ensure patient benefit. A
      more systematic policy approach regarding new technologies is needed, with input
      from balanced groups reviewing evidence of clinical outcomes data to determine
      patient benefit. This paper examines cardiac computed tomography angiography as a
      case study; it proposes procedures designed to ensure that the benefits of new
      technologies justify their costs.

PMID- 17211019
TI  - The value of antihypertensive drugs: a perspective on medical innovation.
AB  - Using national survey data and risk equations from the Framingham Heart Study, we
      quantify the impact of antihypertensive therapy changes on blood pressures and
      the number and cost of heart attacks, strokes, and deaths. Antihypertensive
      therapy has had a major impact on health. Without it, 1999-2000 average blood
      pressures (at age 40+) would have been 10-13 percent higher, and 86,000 excess
      premature deaths from cardiovascular disease would have occurred in 2001.
      Treatment has generated a benefit-to-cost ratio of at least 6:1, but much more
      can be achieved. More effective use of antihypertensive medication would have an
      impact on mortality akin to eliminating all deaths from medical errors or
      accidents.

PMID- 17211020
TI  - The value of coronary heart disease care for the elderly: 1987-2002.
AB  - We examine trends in the value of coronary heart disease (CHD) care in the United
      States over a fifteen-year period, finding major improvements in life expectancy
      from investment in CHD care for the elderly. For those with acute myocardial
      infarction (AMI), the value of care is good, although medical management might
      provide higher value than revascularization. Progress also has been made in
      preventing AMI. Overall, the value of our CHD spending is quite good. Despite
      this wise investment of resources to date, considerable opportunities remain for
      additional investment to improve the adoption of valuable but underused health
      services.

PMID- 17211021
TI  - Getting the price right: Medicare payment rates for cardiovascular services.
AB  - Specialized, physician-owned cardiac hospitals have grown rapidly. Physicians
      have also expanded their capability to provide cardiovascular diagnostic services
      in their offices. In this paper we consider evidence of errors in Medicare's
      prices for hospital care and physician services and discuss ways to improve the
      accuracy of those prices. We find that recent proposals to change the inpatient
      prospective payment system would help dampen hospitals' financial incentives to
      favor some kinds of patients and related investments. For the physician fee
      schedule, we suggest that the Centers for Medicare and Medicaid Services (CMS)
      review the accuracy of prices for high-growth diagnostic services.

PMID- 17211022
TI  - Will the surgical world become flat?
AB  - We obtained price and quality information for nonurgent coronary artery bypass
      graft (CABG) surgery from a sample of internationally patronized hospitals in low
      wage countries. We found rising quality standards, availability of U.S.-trained
      physicians, and prices far below insurer-negotiated U.S. prices. The price
      differentials easily accommodated the incentive specified as a condition for
      surgery abroad by about 30 percent of surveyed households with a sick member.
      These findings foreshadow growth in offshoring of expensive nonemergency
      surgeries among increasingly cost-sensitive U.S. consumers and purchasers.

PMID- 17211023
TI  - National health spending in 2005: the slowdown continues.
AB  - In 2005, U.S. health care spending increased 6.9 percent to almost 2.0 trillion
      dollars, or 6,697 dollars per person. The health care portion of gross domestic
      product (GDP) was 16.0 percent, slightly higher than the 15.9 percent share in
      2004. This third consecutive year of slower health spending growth was largely
      driven by prescription drug expenditures. Spending for hospital and physician and
      clinical services grew at similar rates as they did in 2004.

PMID- 17211024
TI  - Health care spending growth: how different is the United States from the rest of
      the OECD?
AB  - This paper compares the long-term (1970-2002) rates of real growth in health
      spending per capita in the United States and a group of high-income countries in
      the Organization for Economic Cooperation and Development (OECD). Real health
      spending growth is decomposed into population aging, overall economic growth, and
      excess growth. Although rates of aging and overall economic growth were similar,
      annual excess growth was much higher in the United States (2.0 percent) versus
      the OECD countries studied (1.1 percent). That difference, which is of an
      economically important magnitude, suggests that country-specific institutional
      factors might contribute to long-term health spending trends.

PMID- 17211025
TI  - U.S. trends in CABG hospital volume: the effect of adding cardiac surgery
      programs.
AB  - Hospital coronary artery bypass graft (CABG) volume is inversely related to
      mortality--with low-volume hospitals having the highest mortality. Medicare data
      (1992-2003) show that the number of CABG procedures increased from 158,000 in
      1992 to a peak of 190,000 in 1996 and then fell to 152,000 in 2003, while the
      number of hospitals performing CABG increased steadily. Predictably, the
      proportion of CABG procedures performed at low-volume hospitals increased, and
      the proportion in high-volume hospitals declined. An unintended consequence of
      starting new cardiac surgery programs is declining CABG hospital volume--a side
      effect that might increase mortality.

PMID- 17211026
TI  - Use and in-hospital mortality associated with two cardiac procedures, by sex and
      age: national trends, 1990-2004.
AB  - This study used data from the National Hospital Discharge Survey to examine sex-
      and age-specific trends in use and in-hospital mortality associated with coronary
      artery bypass graft (CABG) and percutaneous coronary intervention (PCI) among
      adults age forty-five and older during 1990-2004. Although use rates for PCI
      increased 58 percent over the study period, CABG use rates declined. In-hospital
      death rates declined or stayed the same even though comorbidities increased for
      patients who received the procedures. PCI and CABG use rates for men were at
      least twice those for women, although women generally had more comorbidities and
      higher in-hospital death rates.

PMID- 17211027
TI  - Better late than never: workforce supply implications of later entry into
      nursing.
AB  - Although the number of people entering nursing in their early to mid-twenties
      remains at its lowest point in forty years, large numbers of people are entering
      the profession in their late twenties and early thirties. And although it remains
      unclear why people are becoming nurses later, there is evidence that nursing is
      attracting interest from different segments of the potential workforce than it
      was in the 1970s and 1980s. We analyze these trends using data through 2005 and a
      revised forecast model that still predicts a nurse shortage by 2020, but a
      smaller one than previously forecast.

PMID- 17211028
TI  - Should patients receive secondary prevention medications for free after a
      myocardial infarction? An economic analysis.
AB  - Taken in combination, aspirin, beta-blockers, angiotensin-converting enzyme (ACE)
      inhibitors, and statins (combination pharmacotherapy) greatly reduce cardiac
      events. These therapies are underused, even among patients with drug insurance.
      Out-of-pocket spending is a key barrier to adherence. We estimated the impact of
      providing combination pharmacotherapy without cost sharing ("full coverage") to
      insured patients after a myocardial infarction (MI). Under base-case assumptions,
      compared to standard coverage, three years of full coverage will reduce mortality
      and reinfarction rates and will save 5,974 per patient. Our analysis suggests
      that covering combination therapy for such patients will save both lives and
      money.

PMID- 17211029
TI  - Physician practice size and variations in treatments and outcomes: evidence from
      Medicare patients with AMI.
AB  - Little is known about the relationships between physician practice size and
      patient treatments or outcomes. We examined whether the practice size of
      attending physicians was related to within-hospital differences in care for
      Medicare patients with acute myocardial infarction (AMI). We found that patients
      treated by solo physicians were less likely to receive cardiac catheterization
      and angioplasty within a day of admission and more likely to die than other
      patients in the same hospital, even after a number of patient and physician
      characteristics were taken into account. These differences suggest that solo
      practitioners are less likely to follow guidelines calling for quick use of
      angioplasty.

PMID- 17211030
TI  - The value of electronic health records in community health centers: policy
      implications.
AB  - This paper analyzes the costs and benefits of electronic health records (EHRs) in
      six community health centers (CHCs) that serve disadvantaged patients. EHR
      related benefits for most study CHCs did not pay for ongoing EHR costs, yet
      quality improvement (QI) was substantial. Compared to private practices, CHCs
      cannot use EHRs to increase visit coding levels and revenues, yet they likely use
      EHRs more aggressively for QI, which raises equity questions. The evidence
      suggests that policies are needed that help CHCs to afford EHRs and produce more
      EHR-related QI gains, including through grants and QI performance rewards.

PMID- 17211031
TI  - Disclosure of medical injury to patients: an improbable risk management strategy.
AB  - Pressure mounts on physicians and hospitals to disclose adverse outcomes of care
      to patients. Although such transparency diverges from traditional risk management
      strategy, recent commentary has suggested that disclosure will actually reduce
      providers' liability exposure. We tested this theory by modeling the litigation
      consequences of disclosure. We found that forecasts of reduced litigation volume
      or cost do not withstand close scrutiny. A policy question more pressing than
      whether moving toward routine disclosure will expand litigation is the question
      of how large such an expansion might be.

PMID- 17211032
TI  - Heart of the uninsured.

PMID- 17211033
TI  - Good for harvest, bad for planting.

PMID- 17211034
TI  - Quality of care for acute myocardial infarction at urban safety-net hospitals.
AB  - Safety-net hospitals are experiencing increasing financial strains, possibly
      affecting their quality of care. We compare quality at safety-net and non-safety
      net urban hospitals for Medicare beneficiaries admitted with acute myocardial
      infarction (AMI). Although safety-net hospitals had modestly higher risk
      standardized thirty-day all-cause mortality rates and modestly lower adherence to
      quality-of-care performance measures than non-safety-net hospitals, there was
      much heterogeneity among safety-net hospitals and substantial overlap with non
      safety-net hospitals. We examine the implications of these findings for the
      millions of vulnerable Americans who rely on safety-net hospitals for their care.

PMID- 17211035
TI  - Prescription drugs and the changing concentration of health care expenditures.
AB  - Health care expenditures are highly concentrated in the United States, with a
      small fraction of the population accounting for a large share of total health
      spending. This concentration has proved remarkably stable over time; however, the
      degree of concentration has declined over the past decade. Using data from the
      1996-2003 Medical Expenditure Panel Survey (MEPS), we explore why. We find that
      rapid growth in prescription drug spending, which is diffused over a large
      fraction of the population, versus slower growth in spending for inpatient care
      largely accounts for the recent change in concentration. We discuss the potential
      implications for current cost containment and reform efforts.

PMID- 17211036
TI  - Coping with SCHIP enrollment caps: lessons from seven states' experiences.
AB  - Seven states with separate (as opposed to Medicaid expansion) State Children's
      Health Insurance Programs (SCHIP) implemented enrollment caps during the 2001
      2003 recession. Interviews with SCHIP officials and Covering Kids and Families
      grantees in these states examined implementation policies and their effects on
      enrollment, outreach, and public support. Enrollment caps were generally
      maintained for less than a year and resulted in large spending reductions, but
      enrollment declined steeply. Most key informants indicated that caps were
      preferable to reversals of simplified enrollment, comprehensive benefits, and low
      cost sharing and thus offered policymakers an important tool for controlling
      costs.

PMID- 17211037
TI  - Estimates of health insurance coverage: comparing state surveys with the current
      population survey.
AB  - The Census Bureau produces annual state-level estimates of health insurance
      coverage using the Current Population Survey (CPS) Annual Social and Economic
      Supplement. Many states also conduct their own population surveys of health
      insurance status; in most cases, the state survey estimates of uninsurance are
      lower than the estimates produced by the CPS. This discrepancy fuels debate about
      the true count of uninsured Americans and changes in that number over time. This
      paper compares state survey and CPS estimates of uninsurance, highlights key
      reasons for these differences, and discusses the policy implications of this
      persistent discrepancy.

PMID- 17211038
TI  - RAND/Hartford initiative to build interdisciplinary geriatric health care
      research centers.
AB  - A RAND/John A. Hartford Foundation initiative, Building Interdisciplinary
      Geriatric Health Care Research Centers, seeks to promote such research through
      developing innovative clinical and health services interventions.
      Interdisciplinary education, mentoring, and training opportunities, particularly
      for junior investigators, are the critical components necessary to foster
      multiprofessional research endeavors.

PMID- 17211041
TI  - Methodology on adverse events.

PMID- 17211042
TI  - Pre-deadline data reporting by some hospitals.

PMID- 17211043
TI  - Feds need to create standards and databases.

PMID- 17211045
TI  - [Competency and responsibility].

PMID- 17211046
TI  - [Agomelatine: the first "melatoninergic" antidepressant].
AB  - The intimate relationship between depressive disorders and biological rhythm
      disturbances has long been known. One major component in diurnal rhythm
      regulation in mammals, like humans, is the melatonin axis and its close
      connections with serotonergic and noradrenergic structures. In major depression
      various functional anomalies have been shown in all of these systems. Agomelatine
      is a novel antidepressant with direct agonist activity at the melatonin MT1 and
      MT2 receptors, and a selective antagonist action at the serotonin 5HT2C receptor.
      It has no measurable affinity to any other known receptor. In animal models
      agomelatine has antidepressant-like and anxiolytic-like properties, it promotes
      sleep, and is able to resynchronize various experimentally uncoupled or phase
      shifted biological rhythms. In randomized and controlled clinical trials
      agomelatine appears to be an effective antidepressant, comparable to standard
      SSRI/SNRI drugs, with excellent safety and tolerability profile. It usually
      produces mild and transient side effects, similar to those seen in patients
      receiving placebo. Sleep architecture and subjective measures of sleep quality
      may also respond favorably. Agomelatine causes significantly less sexual
      dysfunction than a reference SNRI. No discontinuation symptoms have been observed
      upon abrupt withdrawal. The overall dropout rates in the clinical trials have
      been remarkably low, suggesting good acceptability and compliance. Even though
      most current antidepressants are effective, they also have weaknesses; therefore
      we still need innovative drugs with novel biochemical actions, faster efficacy
      and/or better tolerability.

PMID- 17211047
TI  - [Sleep-modulation and hypnotics: effects of benzodiazepine-receptor's agonists].
AB  - As binding sites of the alpha-amino butyric acid receptor complexes
      benzodiazepine-receptors offer a possibility to enhance hyperpolarization-based
      inhibition by allosteric modulation. Most of the hypnotic drugs are compounds
      that bind to benzodiazepine receptors. The effects of these drugs are usually
      characterized at a descriptive level, without deliberation of the basic processes
      involved in sleep regulation. This review follows the analysis of hypnotic's
      effect from a perspective of homeostatic, circadian, ultradian and
      microstructural regulation of sleep. In contrast to their expected effect
      benzodiazepines produce a decrease in most of the markers of homeostatic sleep
      regulation. Ligands with non-benzodiazepine structure (cyclopyrrolones,
      imidazopyridines, pyrazolopyrimidines) have a permissive or even stimulating
      effect in some measures of homeostatic sleep regulation. Some benzodiazepines
      have marked chronobiotic effects, while others interfere with circadian rhythms.
      The non- benzodiazepine-type hypnotics are mostly free of chronobiotic effects,
      although zaleplon may increase melatonin release. Given their acute hypothermic
      effect all hypnotic sedatives mimic the circadian signal of sleep initiation.
      Ultradian sleep regulation is largely unaffected by hypnotics. The microstructure
      of sleep as quantified by arousal instability is a sensitive measure of the
      effect of most of the hypnotics. Hypnotic sedatives decrease arousal instability.
      Zolpidem has the strongest effects in microstructural terms.

PMID- 17211048
TI  - [Behavioral phenotypes and cognitive characteristics in mental retardation].
AB  - The authors in a review article deal with characteristic cognitive and behavioral
      features appearing in mental retardations, which later are referred as behavioral
      phenotypes. Nyhan (1972) introduced the term "behavioral phenotype" to describe
      outwardly observable behavior so characteristic of children with genetic
      disorders that its presence suggests the underlying genetic condition. The
      behavioral phenotype is a characteristic pattern of motor, cognitive, linguistic
      and social abnormalities that is consistently associated with a
      biological/neurodevelopmental disorder. This does not mean that the behavior is
      present in all instances but that the probability of its occurrence is increased.
      In the future, more may be learned about brain mechanisms and gene-brain
      interactions by comparing those with behavioral involvement with others with the
      same syndrome but without the behavioral features.

PMID- 17211049
TI  - Neuro-ontological interpretation of spiritual experiences.
AB  - The prevailing neuroscientific paradigm considers information processing within
      the central nervous system as occurring through hierarchically organized and
      interconnected neural networks. The hierarchy of neural networks doesn't end at
      the neuroaxonal level; it incorporates subcellular mechanisms as well. When the
      size of the hierarchical components reaches the nanometer range and the number of
      elements exceeds that of the neuroaxonal system, an interface emerges for a
      possible transition between neurochemical and quantum physical events. "Signal
      nonlocality", accessed by means of quantum entanglement is an essential feature
      of the quantum physical domain. The presented interface may imply that some
      manifestations of altered states of consciousness, unconscious/conscious shifts
      have quantum origin with significant psychosomatic implications. Healing methods
      based on altered states of consciousness and common in spiritual or shamanic
      traditions escape neuroscientific explanations based on classical cognition
      denoted here as "perceptual-cognitive-symbolic" (characteristic of ordinary
      states of consciousness). Another channel of information processing, called
      "direct-intuitive-nonlocal" (characteristic of non-ordinary states of
      consciousness) is required to be introduced for interpretation. The first one is
      capable of modeling via symbolism and is more culturally bound due to its
      psycholinguistic features. The second channel lacks the symbolic mediation,
      therefore it has more transcultural similarity and practically ineffable for the
      first one, though culture specific transliteration may occur. Different
      traditional healing rituals pursue the same end: to destroy "profane"
      sensibility. The ritual use of hallucinogens, the monotonous drumming, the
      repeated refrains, the fatigue, the fasting, the dancing and so forth, create a
      sensory condition which is wide open to the so-called "supernatural". According
      to contemporary anthropological views, the breakdown of ordinary
      sensibility/cognition is not the ultimate goal, but the way to accomplish
      healing, that is psychointegration in the widest sense. From the perspective of
      system theory, integration needs information to be brought into the system.
      According to the presented model, when the coping capability of the "perceptual
      cognitive-symbolic" processing is exhausted in a stressful, unmanageable
      situation, or its influence is eliminated by the use of hallucinogens or in case
      of transcendental meditation, a frame shift occurs, and the "spiritual universe"
      opens up through the "direct-intuitive-nonlocal" channel. There is little chance
      either for a psychointegrative effect, or for a meaningful "opening" without
      ritual context, and with the recreational use of mind altering strategies. .

PMID- 17211050
TI  - Treatment of postpsychotic depression with sertraline in patients with
      schizophrenia--own experience.
AB  - Some authors treated two groups of patients with postpsychotic depression in a
      group of patients with schizophrenia. Sertraline proved better than imipramine in
      view of earlier onset of action and lower incidence, intensity and duration of
      adverse effects and lower risk of schizophrenic symptom recurrence.

PMID- 17211052
TI  - [New formulations of olanzapine in the treatment of acute agitation].
AB  - Agitation is common in patients with acute schizophrenia or bipolar mania, and
      when severe can result in aggressive or violent behaviour. Pharmacotherapy for
      acute psychotic agitation includes the use of antipsychotic and benzodiazepine
      drugs, either alone or in combination. Although oral treatment is preferred,
      options in the pharmacotherapy of acute agitation include the parenteral
      administration of antipsychotics in order to facilitate onset of drug action and
      quickly alleviate symptoms. Until recently only conventional antipsychotic and
      benzodiazepine drugs were available as intramuscular injections. Olanzapine has
      been one of the first atypical antipsychotics available for intramuscular
      administration. Four randomized placebo and comparator controlled , double-blind
      clinical trials have demonstrated the efficacy of olanzapine in reducing acute
      agitation in patients with schizophrenia, bipolar mania and Alzheimer and
      vascular dementia. Evidence from these clinical trials has shown that IM
      olanzapine associated with faster onset of action and more favorable profile of
      adverse events, than monotherapy with IM haloperidol. Current clinical experience
      and one naturalistic study with intramuscular olanzapine suggest that it is
      efficacious and can be safely used in "real world" patients with severe
      agitation. Intramuscular olanzapine have shown ease of transition to same agent
      oral therapy once the acute agitation has diminished. The orally disintegrating
      tablet formulation of olanzapine was effective rapidly reducing psychopathology,
      while improving medication compliance, attitudes and behaviours. This new
      formulation of olanzapine may offer an alternative strategy in the treatment of
      acutely ill, noncompliant schizophrenic patients. Evidence suggests that the new
      formulations of olanzapine should be among the first-line choices in the
      treatment of agitation in acute psychosis. KEYWORDS: olanzapine, intramuscular,
      orally disintegrating tablet, agitation, psychosis.

PMID- 17211053
TI  - [Maintenance pharmacotherapy of schizophrenia: remission and the effectiveness of
      long-acting risperidone therapy].
AB  - Schizophrenia is a severe and devastating psychiatric disorder affecting about 1
      percent of the world's population, is characterized by psychotic episodes,
      negative symptoms and cognitive deficits. New advances in the understanding of
      schizophrenia etiology, course, treatment have increased interest in the
      development of consensus-defined standards for clinical status, improvement,
      remission and recovery. The introduction of standardized remission criteria may
      offer significant opportunities for clinical practice and clinical trials.
      Risperidone is the first atypical antipsychotic available in a long-acting
      injectable formulation. Clinical studies have demonstrated that long-acting
      risperidone is effective and well tolerated in patient with schizophrenia.
      Significant clinical improvement has been reported in patients switched to long
      acting risperidone from other antipsychotic agents. Several patient groups
      (young, first episode, schizoaffective patients) have been shown significant
      benefit from long-acting risperidone. Special patient groups, including, the
      insufficient efficacy, the partial compliance, the suffering from side effect may
      benefit from treatment with long-acting risperidone. This treatment should
      improve the compliance and achieve remission and functional recovery. KEYWORDS:
      schizophrenia, remission, long-acting atypical antipsychotic.

PMID- 17211054
TI  - The adverse effects of hallucinogens from intramural perspective.
AB  - Very recently, after a long-lasting, worldwide moratorium on research of
      hallucinogenic agents, a good number of advanced countries have been revising
      their position, and start to approve testing the physiological and therapeutic
      effects of hallucinogens in human subjects. The purpose of this article is to
      review safety information available in the literature on hallucinogen use, and
      sort out those data from the reported complications of their abuse. Because of
      prohibitory regulations of the last 35 years, there are difficulties in achieving
      this kind of evaluation. Our approach has to be broad, and at times
      retrospective, in contrast to the well-controlled, focused, prospective design of
      the premarketing trials of legal drugs. The article summarizes the analyses in
      anticipation of supportive regulatory changes for the use of hallucinogens in
      well controlled studies and strictly supervised clinical trials. KEYWORDS:
      adverse effects, ayahuasca, N,N-dimethyltryptamine, hallucinogenic agents,
      ibogaine, lysergic acid diethylamide, N-methyl-3,4-methylenedioxyamphetamine,
      psilocybin, therapeutic use.

PMID- 17211055
TI  - [Switching patients with schizophrenia to ziprasidone from conventional or other
      atypical antipsychotics].
AB  - OBJECTIVES: The aim of the study was to assess the efficacy, tolerability and
      safety of ziprasidone in patients with schizophrenia who were already treated
      with conventional or other atypical antipsychotics that had to be switched due
      the lack of efficacy or bad tolerance. METHODS: The study was a 12-week, open
      label, multicenter, non comparative trial on oral ziprasidone. 106 patients with
      DSM-IV schizophrenia were switched to ziprasidone from their previous
      antipsychotic without a washout phase. The study required fixed dosing with
      ziprasidone. For the first week the patient received 80 mg of study drug daily,
      followed for 3 weeks 120 mg/day. Subsequently for 8 weeks either 80 mg, or 120
      mg, or 160 mg total daily dose could be given at the discretion of the
      investigator. Baseline and outcome assessment included Positive and Negative
      Syndrome Scale (PANSS), Clinical Global Impression Severity of Illness Subscale
      (CGI-S) and Global Improvement Subscale (CGI-I), Calgary Depression Scale (CAD),
      Hamilton Depression Scale (HAMD), Drug Attitude Inventory (DAI), Simpson Angus
      Extrapyramidal Symptoms Rating Scale (SAS) and Barnes Akathisia Rating Scale
      (BARS). Changes in overall body weight were also evaluated. RESULTS: After 12
      weeks on ziprasidone therapy, significant improvements were observed on all major
      symptoms measures and subscales. 34 (51,5%) patients (ITT) were rated much or
      very much improved on CGI-I at week 12. The mean SAS score significantly reduced
      during the ziprasidone treatment period (p<0.001). In the DAI ziprasidone
      treatment was also favorable rated. During treatment with ziprasidone for 12
      weeks the body weight of the patients was significantly reduced (mean: 1,2 kg,
      SD=3,79, p=0.002). 58 adverse events occurred in 41 subjects (38.7%), of whom 7
      patients (6.6%) encountered 9 severe adverse events. The adverse events were
      mainly mild and moderate. 15 patients (14.2%) were discontinued from the study
      due to adverse events. The reason for discontinuation in 4 cases was mainly
      insufficient clinical response. CONCLUSION: Switching patients from their
      previous antipsychotic to ziprasidone without a washout phase was generally well
      tolerated and was associated with symptoms improvements 12 weeks later. At least
      50% of patients who needed to be switched because of unsatisfactory efficacy or
      poor tolerance were significantly improved on ziprasidone therapy. The favorable
      safety profile of ziprasidone treatment was consistent with that seen in other
      clinical trials. KEYWORDS: switching, ziprasidone, schizophrenia.

PMID- 17211056
TI  - [Akathisia in the course of olanzapine treatment].
AB  - Olanzapine is a safely and comprehensively applicable atypical antipsychotic
      drug, for the treatment of schizophrenia, and of the mild to sever maniac
      episode. In our case study we describe the appearance of akathisia next to
      olanzapine therapy in the case of a 65 years old woman, and an overview of the
      literature have reference to adverse events of olanzapine.

PMID- 17211057
TI  - High-density lipoproteins (HDL) inhibit endotoxin-induced leukocyte adhesion on
      endothelial cells in rats: effect of the acute-phase HDL.
AB  - High-density lipoprotein (HDL) plays an important role not only in protecting
      against atherosclerosis but also in innate immunity. Several lines of evidence
      showed that HDL could ameliorate the toxic effects of endotoxin or
      lipopolysaccharide (LPS). In this study, we examined whether HDL could inhibit
      LPS-induced leukocyte adhesion on endothelial cells in rats. Normal HDL and acute
      phase HDL (AP-HDL) were purified from plasma of hamsters that received normal
      saline and LPS injection, respectively. Wistar rats were given LPS injection and
      the number of leukocytes adhering to endothelial cells of the mesenteric venules
      was determined using intravital fluorescence videomicroscopy. Intravenous
      injection of LPS enhanced leukocyte adhesion to the mesenteric venules. However,
      when LPS was preincubated with normal HDL, leukocyte adhesion on endothelial
      cells in response to LPS was significantly attenuated in a dose-dependent manner.
      AP-HDL was also able to significantly decrease LPS-induced leukocyte adhesion on
      endothelial cells. It appeared to be more effective than normal HDL since lower
      concentrations were required. This inhibitory effect of HDL was not due to HDL
      itself but it requires preincubation of HDL with LPS. When HDL was separated into
      protein and lipid fractions, it was found that lipid-free apoHDL was able to
      significantly inhibit LPS-induced leukocyte adhesion, whereas lipid component of
      HDL had no effect. In conclusion, HDL, both normal and acute-phase, could inhibit
      an inflammatory effect of LPS on endothelial cells in vivo. AP-HDL was more
      potent than normal HDL in inhibiting LPS-induced leukocyte adhesion, and this
      effect was attributed to the protein component of HDL.

PMID- 17211058
TI  - Effects of vitamin E administration on the hemorheological status and redox
      homeostasis of patients with porphyria cutanea tarda treated with phlebotomy.
AB  - BACKGROUND: Conflicting results were reported about the efficacy of vitamin E (E)
      treatment in porphyria cutanea tarda (PCT). We conducted a study in PCT patients
      to investigate whether E treatment has any additional beneficial effects compared
      with phlebotomy (P) treatment alone on rheological and oxidative stress
      parameters. METHODS: Twenty three patients with sporadic PCT in clinical
      remission and 10 healthy control patients were studied. All patients were treated
      with P prior to the study until clinical remission was achieved. Baseline routine
      laboratory [blood glucose, serum lipids, C-reactive protein (CRP), iron
      metabolism indices, liver function tests], oxidative stress [serum thiobarbituric
      acid reactive substances (TBARS), plasma H-donor activity, plasma free SH-groups,
      erythrocyte glutathion peroxidase activity] and rheological parameters (whole
      blood and plasma viscosity, cell transit time, clogging rate) were measured in
      both groups. Then all PCT patients received E (tocopherol acetate) 200 mg/day for
      8 weeks and at the end of treatment measurements identical to those performed at
      baseline were repeated. RESULTS: Increased urine uroporphyrin, serum CRP, TBARS
      concentrations, whole blood and plasma viscosity and decreased plasma H-donor
      activity, free SH-group level, erythrocyte glutathione peroxidase activity were
      detected in PCT patients treated with P alone compared with control group
      consistent with residual oxidative stress in PCT patients. E treatment decreased
      urine uroporphyrin and serum TBARS concentrations; increased plasma H-donor
      activity and did not influence whole blood and plasma viscosity compared with P
      treatment alone. CONCLUSIONS: E treatment reduced the residual oxidative stress
      and did not influence increased plasma and whole blood viscosity present in PCT
      patients receiving P treatment prior to clinical remission.

PMID- 17211059
TI  - Effect of decreased plasma cholesterol by atorvastatin treatment on erythrocyte
      mechanical properties.
AB  - 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins)
      are the most commonly used cholesterol-lowering drugs, with recent clinical
      trends usually aimed at achieving the lowest possible plasma cholesterol levels.
      Although the effects of increased plasma cholesterol have been previously
      reported, it is not obvious how very low plasma cholesterol levels would affect
      membrane composition and the deformability of red blood cells (RBC). The present
      study investigated the effects of hypocholesterolemia achieved by atorvastatin
      therapy on RBC membrane and mechanical properties in guinea pigs fed a normal
      diet. Two groups of animals were used (atorvastatin-treated, n=12; control n=12),
      and atorvastatin given orally in isotonic phosphate-buffered saline (PBS) at a
      dose of 20 mg/kg/day for a 21-day period. Our results indicate that the
      atorvastatin-treated group had significantly lower plasma total cholesterol
      (17.42+/-1.70 mg/dl), low-density lipoprotein cholesterol (5.25+/-2.22 mg/dl) and
      triglycerides (42.60+/-3.78 mg/dl) than the control group (34.08+/-1.72, 21.17+/
      1.41 and 60.64+/-2.43 mg/dl, respectively). In addition, membrane cholesterol
      content was lower (p<0.0001) and phospholipid content higher (p<0.0001) in the
      atorvastatin-treated group, thus decreasing the cholesterol to phospholipid
      ratio; a significant enhancement in sodium-potassium-ATPase activity also
      occurred. However, in spite the marked changes of plasma and RBC membrane
      composition, there was no change of RBC deformability. Note that although our
      results indicate no adverse rheological alterations, extension of our findings to
      humans requires caution.

PMID- 17211060
TI  - B-flow and B-flow with 3D and SRI postprocessing before intervention and
      monitoring after stenting of the internal carotid artery.
AB  - OBJECTIVE: To investigate the extent to which B-flow and B-flow with 3D
      postprocessing and speckle reduction imaging (SRI) have advantages in appraising
      the morphology of a high-grade stenosis of the internal carotid artery (ICA) for
      preinterventional planning and for postinterventional ultrasonographic follow-up.
      MATERIALS/METHODS: A comparative appraisal of flow with CCDS, power Doppler, B
      flow and 3D B-Flow with SRI were carried out prospectively in 50 patients with
      >70% stenosis according to NASCET criteria in contrast medium-enhanced MRA before
      and after the intervention. After stenting of the internal carotid artery (ICA),
      i.a. digital substraction angiography (DSA) served as an additional reference
      method. RESULTS: In >70% ICA stenosis, simultaneous imaging of the pre-stenotic,
      intra-stenotic and post-stenotic flow was attained with B-flow in 45/90 cases
      (90%), with power Doppler in 39/50 cases (78%) and with CCDS in only 31/50 cases
      (62%). After intervention, a complete detection of flow without overwriting or
      blooming artifacts was achieved in all 50 patients only by B-flow. The
      intrastenotic flow (p<0.05) could be better demarcated against the lumen and the
      vessel wall before the intervention, whereas the flow within the stent could be
      very much better appraised after the intervention (p<0.01) using 3D
      postprocessing of B-flow with additional SRI. Re-stenoses with hypoechoic
      vascular wall changes (3/50 patients) were detected at an early stage using B
      flow. CONCLUSIONS: B-flow technique with SRI and 3D postprocessing can facilitate
      the intrastenotic detection of flow in >70% ICA stenosis with fewer flow
      artifacts. After stenting, the perfused vascular lumen shows less flow artifacts
      compared with CCDS and power Doppler. In order to elucidate hemodynamic changes,
      additional Doppler examinations are still necessary.

PMID- 17211061
TI  - Establishment and biochemical characterization of primary cells of the upper
      aerodigestive tract.
AB  - The upper aerodigestive tract, composed of the oral cavity, the pharynx and the
      esophagus, is a complex system whose components function in both organ-specific
      ways as well in serving as a protective barrier against the enzymes which
      initiate digestion as well as against the mechanical functions which serve to
      ensure movement of food through the upper aerodigestive tract. Given these
      diverse functional requirements, the study of the anatomy and physiology of this
      region are uniquely complex and significantly understudied. The goal of the
      current study was to develop a simple and reproducible method for the isolation,
      growth, and maintenance of primary epithelial cells from the oral cavity, the
      pharynx and the esophagus. In addition, given the increased interest in diseases
      characterized by a loss of mucosal integrity in these areas which is often
      accompanied by a diminished wound healing capability, these cells were
      biochemically characterized with a focus on the components of the extracellular
      matrix remodeling axis including the activity and inhibition of the matrix
      metalloproteinases (MMPs).

PMID- 17211062
TI  - Effect of silver-threads-containing compression stockings on the cutaneous
      microcirculation: a double-blind, randomized cross-over study.
AB  - Recently silver fiber-containing compression stockings for the use in patients
      with chronic venous insufficiency (CVI) were introduced to the market. In order
      to gain some first insight into the effects of these new fabrics on the cutaneous
      microcirculation, a double-blind, randomized cross-over trial was performed in 10
      healthy volunteers. A 3 days run-in phase preceded the (2 x10 days) treatment
      phases and was used to assess the reproducibility of the primary endpoint, which
      was the transcutaneous partial oxygen pressure (tcpO(2)) measured at a probe
      temperature of 44 degrees C in the perimalleolar region of the reference leg in
      supine and dependent leg positions. Coefficients of variation for double measured
      tcpO(2) values were 4.2% (3.1 SD) and 5.8% (6.0 SD) for the leg in supine and
      dependent position. The intra-individual comparison of the effects from both
      treatment phases (value end of treatment - start of treatment) resulted in a
      negative tcpO(2) net balance for the regular hosiery (-0.93 (2.7 SD) mmHg,
      supine; -1.1 (3.5 SD) mmHg, dependent) but a positive net balance for the silver
      fibers containing stockings (0.25 (4.0 SD) mmHg, supine; 1.7 (3.9 SD) mmHg,
      dependent). The inter-treatment differences were statistically significant for
      the leg in a dependent position. The trial provides first evidence that
      interweaving silver threads into regular compression stockings may result in a
      positive effect regarding the nutritive skin perfusion.

PMID- 17211063
TI  - Effects of cyclosporine A on deformability and oxidative stress in the peripheral
      lymphocytes of rats.
AB  - The aim of this study is to investigate the effects of CsA on lymphocyte
      deformability and oxidant-antioxidant system in peripheral lymphocytes in rats.
      Female Wistar Albino rats were injected 10 mg/kg/30 days Sandimmun i.p. the
      control rats were injected 0.9% NaCl. CsA administration caused a significant
      reduction in the deformability of lymphocytes, and produced a significant
      increase in peripheral lymphocytes lipid peroxide level and a significant
      decrease in nitric oxide (NO) level. The activity of superoxide dismutase (SOD)
      in peripheral lymphocytes did not show significant differences between CsA
      administrated and control rats. However the total thiol (t-SH) content of
      lymphocytes was significantly lower in CsA administrated rats. CONCLUSIONS: The
      present data demonstrate that CsA administration increased lipid peroxidation and
      decreased the NO levels and t-SH contents in the peripheral lymphocytes of rats.
      This effect was accompanied by a decrease in lymphocytes deformability. These
      results support the hypothesis that sufficient cellular t-SH concentrations may
      be important to prevent cyclosporin toxicity, and indicate that disturbances in
      lymphocytes rheology may be an additional risk factor in the pathogenesis of side
      effects associated with CsA.

PMID- 17211064
TI  - Erythrocyte deformability does not seem to be altered in Behcet's disease.
AB  - Behcet's disease (BD) is a chronic systemic vasculitis characterized by recurrent
      oral and genital ulcers, uveitis, and skin lesions. It is also associated with an
      increased risk of developing thrombosis, although the prothrombotic mechanisms
      are not clearly defined. The role played by rheological alterations in the
      development of thrombotic events in BD is not well defined, existing little
      information on whether erythrocyte deformability (ED) may be involved in this
      issue. Therefore we aimed to evaluate ED by ektacytometric techniques in a large
      group of patients with BD in a non-active phase of the disease at sampling and in
      a well-matched control group, in order to establish a possible association
      between alterations in ED and the presence of thrombotic events. The patient
      group comprised 45 patients with BD (22 male, 23 female aged 42+/-14 years) and
      the control group comprised 46 healthy volunteers (23 male, 23 female aged 45+/
      13 years). Twelve of the 45 patients with BD had a previous documented history of
      deep vein thrombosis at least six months before entering the study, and the other
      33 did not. Erythrocyte elongation indexes (EI) at the three shear stresses
      tested (EI12, EI30, EI60) were not statistically different between patients and
      controls (EI12: P=0.453; EI30: P=0.411; EI60: P=0.403). There were no significant
      differences in these parameters, either, when patients with and without previous
      thrombotic events were compared (EI12: P=0.272; EI30: P=0.215; EI60: P=0.171).
      Our results suggest that ED is not compromised in BD and does not seem to be
      involved in the development of thrombotic events in these patients.

PMID- 17211065
TI  - Haemostatic variables and their relationship to body mass index and blood
      pressure in adult Nigerians with the sickle cell trait.
AB  - Several studies had assessed the rheological and haemostatic parameters in both
      sickle cell anaemia(HbSS) and haemoglobin AA(HbAA) subjects. The effect of the
      heterogeneous state on these parameters has not been fully determined. Our aim
      was to assess the haemorheological and haemostatic parameters and there
      relationship to body mass index in individuals with the sickle cell trait. Fifty
      eight males (41 HbAA and 17 HbAS) who were neither smokers nor drinkers were
      studied. Body mass index was calculated as weight in Kg divided by height in
      m(2), blood samples were analysed for haematocrit, erythrocyte sedimentation
      rate, platelets, fibrinogen and factor VII by standard methods. There were no
      significant differences in the levels of haemostatic and cardiovascular risk
      factors between the HbAA and HbAS individuals. Fibrinogen correlated positively
      with BMI (r=0.6014, p=0.0107), systolic blood pressure (r=0.4820, p=0.0570),
      diastolic blood pressure (r=0.4699, p=0.0570) in HbAS individuals. The body mass
      index also correlated positively with diastolic blood pressure (r=0.5182,
      p<0.05), and systolic blood pressure (r=0.6189, p<0.01). Positive associations
      were also found between fibrinogen and body mass index (r=0.5012, p=0.0008), and
      fibrinogen and haematocrit (r=0.3696, r=0.0174) respectively in HbAA subjects. We
      conclude that the lack of significant difference in both haemorheological and
      cardiovascular risk factors in HbAS and HbAA subjects has further supported the
      observation that HbAS is a benign condition under physiological settings. Also
      the positive associations of fibrinogen with other cardiovascular risk factors
      have further underscored the central role of fibrinogen as an independent risk
      factors in the development of cardiovascular diseases.

PMID- 17211066
TI  - Progress in research into radiation damage in cryo-cooled macromolecular
      crystals.

PMID- 17211067
TI  - Dose dependence of radiation damage for protein crystals studied at various X-ray
      energies.
AB  - Radiation damage to protein crystals is the most serious problem in obtaining
      accurate structures from protein crystallography. In order to examine the photon
      energy dependence of radiation damage, 12 to 15 data sets from each of nine
      tetragonal lysozyme crystals were collected at nine different X-ray energies
      (6.5, 7.1, 8.3, 9.9, 12.4, 16.5, 20.0, 24.8 and 33.0 keV) using beamline BL41XU
      at SPring-8. All results were compared on the basis of absorbed dose, expressed
      in Gray (Gy). Crystallographic statistics, such as the values of lattice
      constants, R(merge) and I/sigma(I), for each data set degraded at all nine
      energies as the exposure time for each crystal increased. In all data sets,
      radiation damage was observed after the absorbed dose exceeded 10(6) Gy. However,
      from the point of view of crystallographic statistics normalized to the absorbed
      dose, no clear dependence on photon energy was observed in these results.
      Structural refinement showed that the average B-factor for the last data set was
      larger than that for the first data set at all energies tested. However, no
      energy dependence of radiation damage on B-factor was found. Furthermore,
      disruption of disulfide bonds due to radiation damage was observed in electron
      density maps even at the highest photon energy (33 keV) used in this study.
      Therefore, these results suggest that radiation damage in the energy range
      investigated could be evaluated based on absorbed dose without energy dependence,
      and that it is important to minimize the absorbed dose in a crystal sample for
      obtaining an accurate protein structure.

PMID- 17211068
TI  - Cryoradiolytic reduction of crystalline heme proteins: analysis by UV-Vis
      spectroscopy and X-ray crystallography.
AB  - The X-ray crystallographic analysis of redox-active systems may be complicated by
      photoreduction. Although radiolytic reduction by the probing X-ray beam may be
      exploited to generate otherwise short-lived reaction intermediates of
      metalloproteins, it is generally an undesired feature. Here, the X-ray-induced
      reduction of the three heme proteins myoglobin, cytochrome P450cam and
      chloroperoxidase has been followed by on-line UV-Vis absorption spectroscopy. All
      three systems showed a very rapid reduction of the heme iron. In chloroperoxidase
      the change of the ionization state from ferric to ferrous heme is associated with
      a movement of the heme-coordinating water molecule. The influence of the energy
      of the incident X-ray photons and of the presence of scavengers on the apparent
      reduction rate of ferric myoglobin crystals was analyzed.

PMID- 17211069
TI  - The many faces of radiation-induced changes.
AB  - During diffraction experiments even cryo-cooled protein crystals can be
      significantly damaged due to chemical and physical changes induced by absorbed X
      ray photons. The character and scale of the observed effects depend strongly on
      the temperature and the composition of crystals. The absorption of radiation
      energy results in incremental regular changes to the crystal structure, making
      its impact on the process of solving the structure strongly correlated with other
      experimental variables. An understanding of all the dependencies is still limited
      and does not allow for a precise prediction of the outcome of a particular
      diffraction experiment. Results are presented of diffraction experiments
      performed under different experimental conditions. The influence of temperature
      and crystal composition on different characteristics of radiation damage is
      analyzed. The observed effects are discussed in terms of their impact on data
      processing and phasing procedures.

PMID- 17211070
TI  - Modelling and refining site-specific radiation damage in SAD/MAD phasing.
AB  - Site-specific radiation damage on anomalously scattering sites can be used to
      generate additional phase information in standard single- or multi-wavelength
      anomalous diffraction (SAD or MAD) experiments. In this approach the data are
      kept unmerged, down to the Harker construction, and the evolution of site
      specific radiation damage as a function of X-ray irradiation is explicitly
      modelled and refined in real space. Phasing power is generated through the
      intensity differences of symmetry-related reflections or repeated measurements of
      the same reflection recorded at different X-ray doses. In the present
      communication the fundamentals of this approach are reviewed and different models
      for the description of site-specific radiation damage are presented. It is shown
      that, in more difficult situations, overall radiation damage may unfold on a time
      scale that is similar to the evolution of site-specific radiation damage or to
      the total time that is required to record a complete data set. In such cases the
      quality of the phases will ultimately be limited by the effects of overall
      radiation damage.

PMID- 17211071
TI  - A comparison of SAD and two-wavelength MAD phasing for radiation-damaged Se-MET
      crystals.
AB  - Although a case has been made that single-wavelength anomalous dispersion (SAD)
      is the optimal strategy for data collection in the presence of radiation damage,
      two-wavelength MAD experiments at the inflection and a high-energy remote point
      of the absorption edge have been shown to be a potentially successful alternative
      method. In order to further investigate the performance of both data collection
      strategies, a comparison of SAD and MAD phasing was carried out for increasingly
      damaged data sets from three different seleno-methionine protein samples
      collected under similar experimental conditions. In all but one example the MAD
      phases appeared to be less affected than SAD phases with increasing exposure to X
      rays, and had a better overall success rate, indicating that this method should
      be given serious consideration when dealing with radiation-sensitive crystals.
      Simultaneous data collection in wedges at all wavelengths seems to be a very
      important factor in the success of MAD experiments; the decreased absorbed dose
      resulting from eschewing data collection at the maximum f '' wavelength may play
      a less important role. Specific radiation damage to the selenium atoms is found
      to be a minor effect compared with the effect on the anomalous dispersion signal,
      although potentially large enough to be a useful contribution to phasing in both
      SAD and MAD experiments.

PMID- 17211073
TI  - Radioprotectant screening for cryocrystallography.
AB  - Radiation damage continues to present a problem to crystallographers using
      cryocooled protein crystals at third-generation synchrotrons. Free-radical
      scavengers have been suggested as a possible means of reducing the rate of this
      damage. The screening of a large number of potential radioprotectants was
      undertaken with an online microspectrophotometer using cystine and cysteine to
      model protein disulfide bonds and thiol groups, respectively. Oxidized alpha
      lipoic acid was tested as a possible model disulfide bond. The evidence for the
      effectiveness of ascorbate as a radioprotectant was strengthened, and quinone,
      2,2,6,6-tetramethyl-4-piperidone, and reduced dithiothreitol showed promise as
      radioprotectants.

PMID- 17211072
TI  - XANES measurements of the rate of radiation damage to selenomethionine side
      chains.
AB  - The radiation-induced disordering of selenomethionine (SeMet) side chains
      represents a significant impediment to protein structure solution. Not only does
      the increased B-factor of these sites result in a serious drop in phasing power,
      but some sites decay much faster than others in the same unit cell. These radio
      labile SeMet side chains decay faster than high-order diffraction spots with
      dose, making it difficult to detect this kind of damage by inspection of the
      diffraction pattern. The selenium X-ray absorbance near-edge spectrum (XANES)
      from samples containing SeMet was found to change significantly after application
      of X-ray doses of 10-100 MGy. Most notably, the sharp ;white line' feature near
      the canonical Se edge disappears. The change was attributed to breakage of the
      Cgamma-Se bond in SeMet. This spectral change was used as a probe to measure the
      decay rate of SeMet with X-ray dose in cryo-cooled samples. Two protein crystal
      types and 15 solutions containing free SeMet amino acid were examined. The damage
      rate was influenced by the chemical and physical condition of the sample, and the
      half-decaying dose for the selenium XANES signal ranged from 5 to 43 MGy. These
      decay rates were 34- to 3.8-fold higher than the rate at which the Se atoms
      interacted directly with X-ray photons, so the damage mechanism must be a
      secondary effect. Samples that cooled to a more crystalline state generally
      decayed faster than samples that cooled to an amorphous solid. The single
      exception was a protein crystal where a nanocrystalline cryoprotectant had a
      protective effect. Lowering the pH, especially with ascorbic or nitric acids, had
      a protective effect, and SeMet lifetime increased monotonically with decreasing
      sample temperature (down to 93 K). The SeMet lifetime in one protein crystal was
      the same as that of the free amino acid, and the longest SeMet lifetime measured
      was found in the other protein crystal type. This protection was found to arise
      from the folded structure of the protein molecule. A mechanism to explain
      observed decay rates involving the damaging species following the electric field
      lines around protein molecules is proposed.

PMID- 17211074
TI  - Specific radiation damage to acidic residues and its relation to their chemical
      and structural environment.
AB  - Intense synchrotron radiation produces specific structural and chemical damage to
      crystalline proteins even at 100 K. Carboxyl groups of acidic residues (Glu, Asp)
      losing their definition is one of the major effects observed. Here, the
      susceptibilities to X-ray damage of acidic residues in tetrameric malate
      dehydrogenase from Haloarcula marismortui are investigated. The marked excess of
      acidic residues in this halophilic enzyme makes it an ideal target to determine
      how specific damage to acidic residues is related to their structural and
      chemical environment. Four conclusions are drawn. (i) Acidic residues interacting
      with the side-chains of lysine and arginine residues are less affected by
      radiation damage than those interacting with serine, threonine and tyrosine side
      chains. This suggests that residues with higher pK(a) values are more vulnerable
      to damage than those with a lower pK(a). However, such a correlation was not
      found when calculated pK(a) values were inspected. (ii) Acidic side-chains
      located in the enzymatic active site are the most radiation-sensitive ones. (iii)
      Acidic residues in the internal cavity formed by the four monomers and those
      involved in crystal contacts appear to be particularly susceptible. (iv) No
      correlation was found between radiation susceptibility and solvent accessibility.

PMID- 17211075
TI  - Tracking X-ray-derived redox changes in crystals of a methylamine
      dehydrogenase/amicyanin complex using single-crystal UV/Vis
      microspectrophotometry.
AB  - X-ray exposure during crystallographic data collection can result in unintended
      redox changes in proteins containing functionally important redox centers. In
      order to directly monitor X-ray-derived redox changes in trapped oxidative half
      reaction intermediates of Paracoccus denitrificans methylamine dehydrogenase, a
      commercially available single-crystal UV/Vis microspectrophotometer was installed
      on-line at the BioCARS beamline 14-BM-C at the Advanced Photon Source, Argonne,
      USA. Monitoring the redox state of the intermediates during X-ray exposure
      permitted the creation of a general multi-crystal data collection strategy to
      generate true structures of each redox intermediate.

PMID- 17211076
TI  - X-ray radiation-induced damage in DNA monitored by online Raman.
AB  - High-quality Raman spectra have been collected on single DNA crystals kept at 100
      K in a flow of cold nitrogen gas prior, during and after macromolecular
      crystallography (MX) data collection. The non-symmetric bending vibration for C
      Br bonds in 8-bromo-2'-deoxyguanosine has been unambiguously identified at 293
      cm(-1) in the non-resonant Raman spectra. The breakage of this bond could be
      monitored by the continuous recording of Raman spectra during X-ray exposure, and
      its decay versus dose could be directly correlated with the loss of the bromide
      definition within the electron-density maps as determined with MX.

PMID- 17211077
TI  - Non-invasive measurement of X-ray beam heating on a surrogate crystal sample.
AB  - Cryocooling is a technique routinely used to mitigate the effects of secondary
      radiation damage on macromolecules during X-ray data collection. Energy from the
      X-ray beam absorbed by the sample raises the temperature of the sample. How large
      is the temperature increase and does this reduce the effectiveness of
      cryocooling? Sample heating by the X-ray beam has been measured non-invasively
      for the first time by means of thermal imaging. Specifically, the temperature
      rise of 1 mm and 2 mm glass spheres (sample surrogates) exposed to an intense
      synchrotron X-ray beam and cooled in a laminar flow of nitrogen gas is
      experimentally measured. For the typical sample sizes, photon energies, fluxes,
      flux densities and exposure times used for macromolecular crystallographic data
      collection at third-generation synchrotron radiation sources and with the sample
      accurately centered in the cryostream, the heating by the X-ray beam is only a
      few degrees. This is not sufficient to raise the sample above the amorphous
      ice/crystalline-ice transition temperature and, if the cryostream cools the
      sample to 100 K, not even enough to significantly enhance radiation damage from
      secondary effects.

PMID- 17211078
TI  - Radiation damage to protein specimens from electron beam imaging and diffraction:
      a mini-review of anti-damage approaches, with special reference to synchrotron X
      ray crystallography.
AB  - Recent research progress using X-ray cryo-crystallography with the photon beams
      from third-generation synchrotron sources has resulted in recognition that this
      intense radiation commonly damages protein samples even when they are held at 100
      K. Other structural biologists examining thin protein crystals or single particle
      specimens encounter similar radiation damage problems during electron diffraction
      and imaging, but have developed some effective countermeasures. The aim of this
      concise review is to examine whether analogous approaches can be utilized to
      alleviate the X-ray radiation damage problem in synchrotron macromolecular
      crystallography. The critical discussion of this question is preceded by
      presentation of background material on modern technical procedures with electron
      beam instruments using 300-400 kV accelerating voltage, low-dose exposures for
      data recording, and protection of protein specimens by cryogenic cooling; these
      practical approaches to dealing with electron radiation damage currently permit
      best resolution levels of 6 A (0.6 nm) for single particle specimens, and of 1.9
      A for two-dimensional membrane protein crystals. Final determination of the
      potential effectiveness and practical value of using such new or unconventional
      ideas will necessitate showing, by experimental testing, that these produce
      significantly improved protection of three-dimensional protein crystals during
      synchrotron X-ray diffraction.

PMID- 17211080
TI  - On the design of ultrafast shutters for time-resolved synchrotron experiments.
AB  - A comprehensive treatment of the limitations and possibilities for single-pulse
      selection in synchrotron operating modes with approximately 150 ns bunch
      separation, as occurs in the standard operating mode at the Advanced Photon
      Source, is presented. It is shown that the strength of available materials and
      allowable kinetic energy build-up limit single-bunch selection for this
      separation to sample sizes of approximately 100 microm, and that for minimization
      of kinetic energy build-up it is preferable to increase the r.p.m. within
      physically acceptable limits rather than increase the disc radius to obtain a
      desirable peripheral speed. A slight modification of the equal-bunch spacing
      standard fill patterns is proposed that allows use of samples as large as 500
      microm. The corresponding peripheral speed of the chopper wheel is approximately
      600 m s(-1), which is within the limits of high-strength titanium alloys. For
      smaller samples, peripheral speeds are proportionally lower. Versatility can be
      achieved with interchangeable chopper wheels and the use of different
      orientations of the rotation axis relative to the X-ray beam, which opens the
      possibility of larger, rather than one-of-a-kind, production runs.

PMID- 17211079
TI  - Plastic-embedded protein crystals.
AB  - Rapid vitrification followed by the replacement of the vitrified water by a
      solvent (freeze substitution) and then resin is a widely used procedure for
      preparing biological samples for electron microscopy. The resulting plastic
      embedded samples permit convenient room-temperature sectioning (microtomy) and
      can yield well preserved cellular structures. Here this procedure has been
      applied to crystalline protein samples, and it is shown that it is possible to
      freeze-substitute vitrified crystals while preserving some of their original
      diffraction properties. The plastic-embedded crystals were used to collect a
      series of complete room-temperature data sets at a powerful macromolecular
      crystallography synchrotron beamline. Whereas one normally observes specific
      damage to disulfide bonds upon X-ray radiation, no such damage was seen for the
      plastic-embedded sample. The X-ray diffraction data allowed an initial atomic
      analysis to be made of the effects of freeze-substitution and plastic embedding
      on biological samples.

PMID- 17211081
TI  - A sagittally focusing double-multilayer monochromator for ultrafast X-ray imaging
      applications.
AB  - The development of a sagittally focusing double-multilayer monochromator is
      reported, which produces a spatially extended wide-bandpass X-ray beam from an
      intense synchrotron bending-magnet source at the Advanced Photon Source, for
      ultrafast X-ray radiography and tomography applications. This monochromator
      consists of two W/B(4)C multilayers with a 25 A period coated on Si single
      crystal substrates. The second multilayer is mounted on a sagittally focusing
      bender, which can dynamically change the bending radius of the multilayer in
      order to condense and focus the beam to various points along the beamline. With
      this new apparatus, it becomes possible to adjust the X-ray beam size to best
      match the area detector size and the object size to facilitate more efficient
      data collection using ultrafast X-ray radiography and tomography.

PMID- 17211082
TI  - A 3 x 6 arrayed CCD X-ray detector for continuous rotation method in
      macromolecular crystallography.
AB  - A 3 x 6 arrayed charge-coupled device (CCD) X-ray detector has been developed for
      the continuous-rotation method in macromolecular crystallography at the Photon
      Factory. The detector has an area of 235.9 mm x 235.9 mm and a readout time of
      1.9 s. The detector is made of a 3 x 6 array of identical modules, each module
      consisting of a fiber-optic taper (FOT), a CCD sensor and a readout circuit. The
      outputs from 18 CCDs are read out in parallel and are then digitized by 16-bit
      analog-to-digital converters. The advantage of this detector over conventional
      FOT-coupled CCD detectors is the unique CCD readout scheme (frame transfer) which
      enables successive X-ray exposures to be recorded without interruption of the
      sample crystal rotation. A full data set of a lysozyme crystal was continuously
      collected within 360 s (180 degrees rotation, 3 s/1.5 degrees frame). The duty
      cycle ratio of the X-ray exposure to the data collection time was almost 100%.
      The combination of this detector and synchrotron radiation is well suited to
      rapid and continuous data collection in macromolecular crystallography.

PMID- 17211083
TI  - Application of a hybrid pixel detector to powder diffraction.
AB  - Results obtained using a hybrid pixel photon-counting detector in powder
      diffraction experiments are presented. The detector works at room temperature and
      its dynamic response ranges from 0.01 photons pixel(-1) s(-1) up to 10(6) photons
      pixel(-1) s(-1). The pixel sizes are 0.33 mm x 0.33 mm for a total area of 68 mm
      x 68 mm. On recording high-resolution diffraction patterns of powders, a
      reduction of the experimental time by more than a factor of 20 is obtained
      without loss of data quality. The example of an X-zeolite shows that such
      detectors can be used for very demanding anomalous experiments. In situ
      experiments of quenching liquid oxides show that frames of 0.01 s can be achieved
      for studying such processes.

PMID- 17211084
TI  - An off-axis magnetron-sputtering system for in situ studies of artificial
      superlattices growth by synchrotron radiation scattering.
AB  - A sputtering chamber for the growth of artificial superlattices of oxide-based
      materials is described. The chamber is designed to fit into a standard Huber
      eight-circle diffractometer. The chamber serves for investigation with
      synchrotron radiation of growth characteristics of oxide-based artificial
      superlattices in situ. Two Be windows of large area in the vacuum chamber enable
      measurement of reflections of X-rays at entrance and exit angles up to
      approximately 50 degrees . Large perpendicular momentum transfers are practical
      with this apparatus. The possibility of investigating X-ray scattering in situ is
      demonstrated by observation of the effects of the modulation length and the
      stacking period on the growth characteristics of BaTiO(3)/LaNiO(3) artificial
      superlattices.

PMID- 17211085
TI  - Verifying DiffEXAFS measurements with differential X-ray diffraction.
AB  - Differential EXAFS (DiffEXAFS) is a novel technique for measuring atomic
      perturbations on a local scale. Here a complementary technique for such studies
      is presented: differential X-ray diffraction (DiffXRD), which may be used to
      independently verify DiffEXAFS results whilst using exactly the same experimental
      apparatus and measurement technique. A test experiment has been conducted to show
      that DiffXRD can be used to successfully determine the thermal expansion
      coefficient of SrF(2).

PMID- 17211088
TI  - [Therapeutic agents for disorders of bone and calcium metabolism: Ibandronate].
AB  - Ibandronate is a potent nitrogen-containing bisphosphonate that can be
      administered by short (15 - 30 second) intravenous (i.v.) injection in regimens
      with extended dosing intervals; unlike in Caucasian women, the efficacy and
      safety of this formulation is yet to be fully explored in Japanese with
      osteoporosis. A 6-month, multicenter, randomized, double-blind, placebo
      controlled study, involving 228 Japanese women with osteoporosis, was conducted
      to compare the efficacy and safety of the i.v. injection regimens. At 6 months,
      substantial increases in bone mineral density (BMD) were observed at the lumbar
      spine and proximal femur in the active treatment arms. For biochemical markers of
      bone turnover (urinary type I collagen cross linked C-terminal telopeptide [uCTX]
      and bone alkaline phosphatase [BAP]), the 1 mg monthly and 2 mg bi-monthly
      regimens were nominally more effective than the 0.5 mg monthly regimen; all
      ibandronate regimens were superior to placebo. The i.v. ibandronate injections
      were generally well tolerated, with a similar overall adverse event profile to
      placebo. No serious drug-related adverse events were reported. Monthly and bi
      monthly i.v. ibandronate injections effectively reduce bone turnover and increase
      BMD in Japanese women with osteoporosis. Ibandronate injections provide a new
      option for the treatment of osteoporosis.

PMID- 17211089
TI  - [Therapeutic agents for disorders of bone and calcium metabolism: Minodronic acid
      hydrate].
AB  - Minodronic acid hydrate is one of the new-generation bisphosphonates containing
      nitrogen. This drug has an inhibitory effect on bone resorption by suppressing
      the osteoclastic function, and it is being developed as a therapeutic drug of
      osteoporosis. In non-clinical study, the drug has an inhibitory effect on the
      decrease of the bone mineral density and the bone intensity in ovariectomized rat
      osteoporosis models. The one of two Phase III studies, conducted so far,
      indicated that minodronic acid hydrate, administered once daily for 104 weeks,
      reduced the risk of vertebral fracture compared to placebo in postmenopausal
      Japanese women with osteoporosis. The other study conducted that minodronic acid
      hydrate increases the bone mineral density at least equivalent to that of
      alendronate for 48 weeks. The safety analysis in the latest study revealed that
      the adverse events of minodoronic acid hydrate have no statistically significant
      differences from the placebo group. We expect that minodronic acid hydrate will
      be used for a number of patients with osteoporosis as a potent and safe
      domestically created bisphosphonate in the near future.

PMID- 17211090
TI  - [Therapeutic agents for disorders of bone and calcium metabolism: Zoledronic
      acid].
AB  - Intervenous (IV) bisphosphonates are used for cancer patients with hypercalcemia
      of malignancy (HCM) and breast cancer bone metastases (BM). Recently, zoledronic
      acid, the most potent third generation bisphosphonate, has been approved for both
      HCM and BM of broad tumors. It showed 850-fold stronger activity than pamidronate
      in bone resorption assay, and clinical efficacy against multiple cancer bone
      lesion has been confirmed in randomized clinical trials. Zoledronic acid becomes
      one of the most used bisphosphonate for cancer patients in the world, and the
      results of clinical trials for cancer treatment-induced bone loss or
      postmenopausal osteoporosis are now updating.

PMID- 17211091
TI  - [Therapeutic agents for disorders of bone and calcium metabolism: Bazedoxifene].
AB  - Selective estrogen receptor modulators (SERMs) have the potential to provide the
      skeletal benefits of estrogen without the increased risk of uterine and breast
      cancer. Raloxifene, second generation SERM has been approved for the prevention
      and treatment of osteoporosis. Bazedoxifene (BZA, TSE-424Z), novel SERM, acts as
      a tissue selective estrogen antagonist or agonist. Bazedoxifene inhibited bone
      turnover and prevented bone loss caused estrogen deficiency. Furthermore, this
      SERM did not affect the uterine endometrial thickness and reduced serum
      cholesterol. These date suggest that Bazedoxifene is novel potential drug for the
      prevention of osteoporosis in postmenopausal women.

PMID- 17211092
TI  - [Therapeutic agents for disorders of bone and calcium metabolism--Denosumab, a
      fully human monoclocal antibody-targeting RANKL as a therapy for cancer-induced
      bone diseases].
AB  - Receptor activator of nuclear-kappaB ligand (RANKL) is a protein expressed by
      oseoblastic stromal cells, binds to receptor activator of nuclear factor-kappaB
      (RANK) and is the primary mediator of osteoclast differentiation, activation, and
      survival. RANKL is responsible for osteoclast-mediated bone resorption in a broad
      range of conditions and play a key role in establishment and propagation of
      skeletal disease in patients with advanced cancer. Denosumab is a fully human
      monoclonal antibody that binds RANKL with high affinity and specificity and
      inhibits RANKL-RANK interaction, mimicking the endogenous effects of
      osteoprotegerin, a soluble RANKL decoy receptor. In the phase 1 clinical trials
      in healthy post menopausal women and patients with multiple myeloma or breast
      cancer with bone metastasis including Japanese (except for multiple myeloma)
      showed that single and multiple subcutaneous injection of denosumab caused rapid
      and sustained suppression of markers of osteoclastic bone resorption with
      favorable safety profiles. Currently, the larger global clinical trials to
      investigate the effect of this agent for the treatment of cancer-induced bone
      disease as well as osteoporosis are underway.

PMID- 17211094
TI  - [Therapeutic agents for disorders of bone and calcium metabolism--Parathyroid
      hormone in weekly subcutaneous injection].
AB  - The parathyroid hormone (PTH) that is marketed outside Japan is for daily
      administration. It has been proven to increase bone mass and prevent fractures,
      and the effects are very strong. However, data suggest that daily administration
      of PTH increases bone resorption. By contrast, weekly administration of PTH,
      which is being developed in Japan, actually decreases bone resorption, and data
      suggest that this regimen maintains a good balance between bone formation
      (predominant) and bone resorption. Furthermore, it has been reported that weekly
      administration of PTH increases bone mass as much as every day administration of
      PTH, and as such, weekly administration of PTH has the potential to be a useful
      regimen with characteristics that are different from those of daily
      administration of PTH.

PMID- 17211093
TI  - [Therapeutic agents for disorders of bone and calcium metabolism--Teriparatide,
      parathyroid hormone (1-34) as a daily subcutaneous injection].
AB  - Teriparatide is the recombinant N-terminal fragment (1-34) of endogenous human
      parathyroid hormone (PTH) and has been approved and used in many countries
      including the United States and Europe. Treatment with teriparatide 20 microg/day
      for 18 months increased spine bone mineral density (BMD) by approximately 10% and
      reduced the incidence of vertebral fractures by 65% and nonvertebral fragility
      fractures by 53%. Furthermore, the results from paired-biopsy showed that the
      treatment with teriparatide improved bone architecture. Teriparatide is being
      developed in Japan as a treatment for osteoporosis.

PMID- 17211095
TI  - [Therapeutic agents for disorders of bone and calcium metabolism. Development of
      nasal formulation of hPTH (1-34)].
AB  - Intermittent administration of parathyroid hormone (PTH) has been shown to have
      strong anabolic effects on bone. However, the disadvantages associated with daily
      subcutaneous injection therapy are factors influencing patient acceptance and
      compliance. We have developed a nasal spray formula of hPTH (1-34), and found
      that peak serum hPTH (1-34) concentrations after treatment with nasal hPTH (1-34)
      spray are similar to those obtained after administration sc injection of hPTH (1
      34). In order to determine clinical efficacy as well as safety and tolerability
      of nasal hPTH (1-34) spray therapy, a clinical trial was conducted in subjects
      with osteoporosis. Daily nasal hPTH (1-34) spray for 3 months significantly
      increased lumbar bone mineral density (L-BMD) in a dose-dependent manner. In
      addition, it was observed that one part of the L-BMD increases was a result of
      stimulating bone formation by the bone formation marker monitoring.
      Interestingly, bone resorption markers did not increase but were suppressed after
      3 months, suggesting that there may be a different mechanism involved when
      comparing nasal hPTH (1-34) therapy with hPTH (1-34) sc administration.

PMID- 17211096
TI  - [Therapeutic agents for disorders of bone and calcium metabolism: ED-71].
AB  - ED-71 is a new vitamin D receptor ligand, bearing a hydroxypropoxy substituent at
      the 2beta-position of 1alpha, 25 (OH) (2)D(3). In ovariectomized rats, ED-71
      increased lumbar vertebral bone mass and bone strength by inhibiting bone
      resorption and maintaining bone formation without causing hypercalcemia. In a
      randomized, placebo-controlled, double-blinded clinical trial for osteoporotic
      subjects with sufficient vitamin D supply, ED-71 treatment for 12 months can
      effectively increase lumbar and hip bone mineral density in a dose-dependent
      manner without causing sustained hypercalcemia. Serum calcium (Ca) and urinary Ca
      excretion was increased dose-dependently by ED-71 treatment, but it was in normal
      range. These results demonstrate that ED-71 can effectively increase bone mass
      without causing hypercalcemia, and suggest that ED-71 can be a promising
      candidate for the treatment of osteoporosis.

PMID- 17211097
TI  - [Therapeutic agents for disorders of bone and calcium metabolism. Osteoporotic
      fracture prevention by strontium ranelate].
AB  - Bone loss results in osteoporosis and increased susceptibility to bone fractures.
      Importantly, osteoporosis is a major cause of morbidity and mortality in the
      elderly population. With a constantly increasing aging population worldwide,
      early prevention of bone loss is essential for adequate control of this
      condition. Strontium ranelate, an oral treatment for postmenopausal osteoporosis,
      is unique in its mode of action as it is the sole anti-osteoporotic agent that
      both decreases bone resorption and increases bone formation. Its efficacy to
      reduce vertebral and non-vertebral fractures including those of the hip, in
      addition to its safety profile has been demonstrated in the Spinal Osteoporosis
      Therapeutic Intervention (SOTI) and Treatment of Peripheral Osteoporosis (TROPOS)
      clinical studies over 3 years and recently confirmed over the long-term.
      Furthermore, a pre-planned analysis of a sub-group of patients aged 80 years and
      over demonstrated that, currently, strontium ranelate is the only anti
      osteoporotic agent to reduce vertebral and non-vertebral fractures in this age
      group.

PMID- 17211099
TI  - [ASBMR 2006 Report. ASBMR topics on basic research].
AB  - This overview summarizes topics from the 28th Annual Meeting of the American
      Society for Bone and Mineral Research (ASBMR) held at Pennsylvania Convention
      Center on September 15-19, 2006. Out of the 288 orally presented papers, I picked
      up a couple of basic studies from each category of osteoblast, chondrocyte,
      osteoclast, cytokines and hormones.

PMID- 17211098
TI  - [Therapeutic agents for disorders of bone and calcium metabolism. The
      calcimimetic cinacalcet HCl].
AB  - Calcimimetics drug such as cinacalcet suppress the secretion of parathyroid
      hormone by sensitizing parathyroid calcium receptors to extracellular ionized
      calcium. Standard treatment for secondary hyperparathyroidism is associated with
      the risk of hypercalcemia, but cinacalcet don't induce elevation of serum
      calcium. And some studies were reported the use of cinacalcet not only to manage
      primary hyperparathyroidism, but also secondary hyperparathyroidism in
      nondialyzed stage, renal transplant patients and parathyroid carcinoma.

PMID- 17211100
TI  - [ASBMR 2006 Report. Pathophysiology and diagnosis of osteoporosis].
AB  - This is a brief report on the papers related to pathophysiology and diagnosis of
      osteoporosis, which were presented in the 28th annual meeting of American Society
      for Bone and Mineral Research (ASBMR) held in Pennsylvania Convention Center,
      Philadelphia. In this meeting, there were numerous studies on risk factors for
      osteoporosis, since they are indispensable to estimate bone quality which is
      still impossible to quantify. In addition, the osteocytes are being dug out from
      the deep and dark bone lacunae for scientific examination. Very remarkable
      advancement in the mechanisms of the age-related inhibition of bone formation are
      also reported.

PMID- 17211101
TI  - [ASBMR 2006 Report. Treatment of osteoporosis].
AB  - Several papers describing results of new drugs or new formulas for administration
      of drugs for osteoporosis were presented at the annual meeting of the American
      Society for Bone and Mineral Research (ASBMR). For example, quarterly or yearly
      intravenous administration and monthly oral dosage were shown to be effective for
      certain bisphosphonates. Inhibitors for cathepsin K was also reported to increase
      bone mineral density. In addition, some promising drugs are under development.
      There will be more alternatives for the treatment of osteoporosis in the future.

PMID- 17211102
TI  - [Secondary osteoporosis. A review of recent evidence focusing on glucocorticoid
      induced osteoporosis and osteoporosis associated with rheumatoid arthritis].
AB  - Various pathogenic conditions including endocrine, inflammatory, gastrointestinal
      and hematological disorders, medication, and immobilization cause secondary
      osteoporosis. Secondary osteoporosis occurs not only in postmenopausal women but
      also in premenopausal women and men. Therefore, the fractures have a great impact
      on their social lives. Serial articles regarding secondary osteoporosis will
      appear in this journal, especially focused on glucocorticoid-induced osteoporosis
      and osteoporosis associated with rheumatoid arthritis.

PMID- 17211103
TI  - [Hospital-acquired urinary tract infections].
AB  - Urinary tract infections are responsible for 40-60% of all hospital-acquired
      infections. Increased age of patients and comorbid diseases render hospitalized
      patients more susceptible to infection. Almost 80% of hospital-acquired urinary
      tract infections are associated with urinary catheters, and only 5-10% of urinary
      infections are caused by invasive manipulations in the urogenital tract.
      Pathogens of hospital-acquired urinary tract infections are frequently multi
      resistant, and antibiotic therapy can only be successful when the complicating
      factors are eliminated or urodynamic function is restored. For treatment of
      complicated hospital-acquired urinary tract infections, the antibiotics must
      exhibit adequate pharmacodynamic and pharmacokinetic properties: high renal
      clearance of unmetabolized form with good antimicrobial activity in both acidic
      and alkaline urine. For selection of empirical treatment of hospital-acquired
      urinary tract infections, it is necessary to evaluate localization of infection,
      its severity, possible isolates, and the most frequent pathogens in the
      department where patient is treated. The best choice for the starting the
      antimicrobial therapy is the cheapest narrow-spectrum effective antibiotic in the
      treatment of urinary tract infection until microbiological evaluation of
      pathogens will be received. Adequate management of urinary tract infections
      lowers the rate of complications, requirements for antibacterial treatment,
      selection of multi-resistant isolates and is cost effective.

PMID- 17211104
TI  - [Left ventricular remodeling in ischemic heart disease patients with signs and
      symptoms of chronic heart failure: an impact of the long-term exercise training].
AB  - Our study aimed at determining the effects of long-term exercise training on
      cardiorespiratory function and left ventricular remodeling in ischemic heart
      disease patients with the evidence of chronic heart failure, who had undergone a
      successful coronary angioplasty. One hundred thirty-five patients were entered
      into one-year study: 70 patients were assigned to the long-term exercise training
      group, and the remaining 65 persons--to the control group. All the patients were
      subjected to ergospirometry and echocardiography at study entry and at 6 and 12
      months. At the outset, both groups showed no significant difference (P>0.05) in
      terms of ergospirometry findings. However, after 6 months, the rehabilitation
      group demonstrated significant changes (P<0.05) in exercise time, double product,
      RQ, AT VO2, VE/VO2, while the control group displayed no significant changes.
      After 12 months, the patients of rehabilitation group showed further increase in
      exercise time (from 5.6+/-1.9 min to 6.5+/-2.1 min) and AT VO2 (from 17.3+/-7.2
      ml/kg/min to 20.8+/-5.4 ml/kg/min) indices (P<0.05). Those of double product and
      VE/VO2 decreased slightly when compared with findings at 6 months. RQ remained
      virtually at the same level, but significantly differed from the corresponding
      indices at the outset. Echocardiography performed at the entry and at 6 and 12
      months revealed significant changes in systolic left ventricular function among
      the patients of rehabilitation group: wall movement index, ejection fraction as
      well as the left atrial long axis and left ventricular wall thickness.
      Echocardiographic changes indicate a positive impact of complex rehabilitative
      measures on systolic left ventricular function as evidenced by the ejection
      fraction and wall movement index values, as well as by regression of left
      ventricular wall thickness and left atrial long axis. Ergospirometry findings
      allow us to propose that the adequate choice of rehabilitative tools favorably
      affects the cardiovascular system, and this is reflected in exercise time and AT
      VO2 indices.

PMID- 17211105
TI  - [The comparison of visual acuity and contrast sensitivity in patients with
      cataract and age-related macular degeneration implanted with foldable or rigid
      intraocular lenses].
AB  - OBJECTIVE: To evaluate the maximally corrected visual acuity and contrast
      sensitivity under photopic and mesopic conditions with or without glare in
      pseudophakic patients implanted with either foldable or rigid intraocular lenses.
      MATERIAL AND METHODS: A total of 83 patients after cataract surgery were examined
      at baseline and 8-12 weeks later: 47 patients with age-related macular
      degeneration (Group 1) and 36 patients without ocular comorbidities (Group 2).
      Contrast sensitivity was measured using a Ginsburg Box, VSCR-CST-6500. RESULTS:
      Using logistic regression analysis it was revealed that probability of clinically
      significant improvement of contrast sensitivity under photopic conditions with
      and without glare in the patients with implanted foldable lenses increased by 3.1
      times (95% PI 1.6-5.9, P<0.001) compared with the patients with rigid lenses. In
      mesopic conditions with and without glare, it increased by 3.9 and 3.0 times (95%
      PI 1.9-7.8 and 1.6-5.9, respectively, P<0.001) in the patients with foldable
      lenses as compared with the patients with rigid lenses. CONCLUSIONS: The foldable
      intraocular lenses have shown better contrast sensitivity than rigid lenses under
      both mesopic and photopic conditions with or without glare. Postoperatively,
      there was no significant difference in visual acuity concerning the types of the
      implanted intraocular lenses.

PMID- 17211107
TI  - Anterior-posterior versus anterior-lateral electrode position for biphasic
      cardioversion of atrial fibrillation.
AB  - OBJECTIVE: The aim of the study was to assess if the anterior-posterior electrode
      position for the conversion of atrial fibrillation using biphasic waveform shocks
      is more effective and needs less energy compared with the anterior-lateral
      position. BACKGROUND: In several studies, anterior-posterior electrode position
      has been demonstrated to be superior to anterior-lateral position for the
      termination of atrial fibrillation using monophasic waveform shocks, but data
      regarding biphasic shocks are still emerging. PATIENTS AND METHODS: Our
      prospective, randomized study enrolled 103 consecutive patients with atrial
      fibrillation who were referred for elective cardioversion. The electrode position
      was randomly selected to be anterior-lateral (n=55) and anterior-posterior
      (n=48). A step-up protocol of 100, 150, 200, and 300 J biphasic truncated
      exponential waveform shocks was used. RESULTS. Two groups with different paddle
      position were compared. There was no difference in age, gender, body mass index,
      ejection fraction, or left atrial size between the groups. Sinus rhythm
      restoration failed only in one patient in each group. Energy of 100 J was
      sufficiently effective in most patients in both groups. CONCLUSIONS: The anterior
      posterior electrode position during transthoracic cardioversion using biphasic
      waveform shocks has no advantages compared with more comfortable and common
      anterior-lateral position.

PMID- 17211106
TI  - [Association between human serum soluble CD40 ligand, blood lymphocyte and
      neutrophil percentage, and cataract and age-related macular degeneration].
AB  - The aim of the study was to assess the association between the human soluble
      ligand CD40, blood leukocyte count, lymphocyte and neutrophil percentage in
      patients with cataract and age-related macular degeneration. MATERIAL AND
      METHODS: A prospective study was performed on 132 ophthalmologic patients. Group
      1 consisted of 47 patients with cataract and age-related macular degeneration;
      Group 2, of 36 patients just with cataract; Group 3, of 49 patients with age
      related macular degeneration. During the first visit, all the studied patients
      were ophthalmologically examined; their blood leucocyte count, lymphocyte and
      neutrophil percentage were assessed. Soluble CD40 ligand levels were measured in
      17 Group 1 patients, 36 Group 2 patients, and 7 Group 3 patients. RESULTS: The
      percentage of neutrophils in Group 1 and Group 3 patients was greater than in
      Group 2 patients (56.06+/-8.39% vs. 51.08+/-11.73%; p=0.009), whereas the
      respective percentage of lymphocytes was smaller (31.87+/-7.29% vs. 35.72+/
      9.29%; p=0.017). Serum levels of CD40 ligand in Group 1 and Group 3 patients were
      statistically significantly lower than in Group 2 patients (347.10+/-435.05 pg/mL
      vs. 1010.27+/- 653.88 pg/mL; p<0.0001). CONCLUSIONS: An increase in the
      percentage of neutrophils and decrease in the percentage of lymphocytes are
      associated with cataract and age-related macular degeneration, whereas an
      increase in the concentration of CD40 ligand is related to cataract only. No
      statistically significant association between the studied eye disorders and blood
      leukocyte count was found.

PMID- 17211108
TI  - [Assessment of antibiotic use and comparison with recommendations for their
      rational use].
AB  - Irrational and excessive use of antibiotics increases resistance to these
      preparations. Antimicrobial resistance is a serious public health problem
      worldwide. The main goal of our study was to evaluate the use of antibiotics
      (indications, dosage, and treatment duration) in daily family doctors' practice
      and nonadherence to guidelines on rational antibiotic therapy. A retrospective
      study of records regarding the prescription of antibiotics for patients in two
      outpatient settings during the period of January 1, 2005, to December 31, 2005
      was performed in Clinic of Family Medicine at Kaunas University of Medicine.
      Rationality of antibiotic therapy was evaluated according for adherence to
      published guidelines. A descriptive and comparative statistical analysis of data
      was processed with SPSS 13.0 program. There were 2935 patients in both outpatient
      settings (1285 and 1650, respectively). During the period of January 1, 2005, to
      December 31, 2005, antibiotics were prescribed in 210 cases for various reasons
      (71 (33.8%) and 139 (66.2%), respectively). A total of 184 (6.3%) patients
      received antibiotic therapy. It was determined that only in 9.5% of all cases,
      antibiotics were administered in keeping with the recommendations for rational
      antibiotic therapy. Only two treatment cases (1%) were based on bacteriological
      analysis. According to indications, appropriate antibiotics were prescribed in
      42.9% of cases. The dosage of antibiotics was adjusted properly in 56.2% of
      cases, and even in 82.9% of cases, the duration of antibiotic therapy fulfilled
      the guidelines on rational antibiotic use. More rational antibiotic therapy was
      practiced in the second outpatient setting (10.8%) compared to the first
      outpatient setting (7%) (p<0.05). The most irrationally antibiotics were
      prescribed for the treatment of urinary tract and ocular infections.

PMID- 17211109
TI  - [Compliance in psychiatry: results of a survey of depressed patients using orally
      disintegrating tablet].
AB  - As many as 60% of the patients do not follow the therapy recommended by their
      physicians. An important factor that can influence patient's compliance is the
      physician's opinion about the tolerability and safety of prescribed medication.
      However, the efforts of both parties, not only physician but also patient, have
      benefits on the outcome of treatment. Patient's opinion on choosing the form of
      medication is appropriate way ensuring better compliance. The aim of the survey
      was to ascertain the opinion of depressed patients towards a new formulation of
      antidepressant drug, mirtazapine - orally disintegrating tablet Remeron SolTab.
      The study was approved by Lithuanian State Medicines Control Agency and local
      Ethics Committee. A total of 453 depressed patients were included in the survey.
      Most of the patients used a 30-mg dose of Remeron SolTab (n=344, 75.88%). Most of
      the patients (n=189, 41.81%) had a positive opinion about the taste of medication
      ("very pleasant"). According to the results of the survey, 281 (61.95%) used
      Remeron SolTab regularly. However, 129 (28.54%) patients noted that the new drug
      formulation had no influence on the regularity of use. Statistically
      significantly more patients (81.86%) noted that they would choose Remeron SolTab
      compared to the patients who would prefer conventional form of the medication
      (2.21%). In 184 (40.71%) patients, a significant mood improvement was noted. Most
      of the patients (n=246, 54.20%) indicated that mood improved. Based on the
      results of the survey it can be concluded that patient will prefer the drug (or
      its new formulation) he/she liked and thus will follow physician's instructions
      and cooperate with physician more closely. A limitation of this study relates to
      the study design and questionnaire itself, since it was not validated in
      appropriate way. However, the results of the survey are in line with the results
      of the similar surveys from other countries and reflect the general tendencies
      towards antidepressant use.

PMID- 17211111
TI  - Trends in the consumption of antidepressant drugs in Lithuania in 2002-2004.
AB  - OBJECTIVE: To evaluate trends in the use of antidepressant drugs in Lithuania
      between 2002 and 2004 and to perform cost-minimization and reference price
      analysis enabling more rational use of financial resources of national health
      system. MATERIAL AND METHODS: The data on sales of antidepressant drugs in
      Lithuanian over a 3-year period (2002-2004) were obtained from IMS Health Inc.
      database. Data were calculated by defined daily dose (DDD) methodology and
      expressed in DDDs per 1000 inhabitants per day. DU90% was used as the quality
      indicator of the drug prescribing. The pharmacoeconomic analysis of
      antidepressant drugs was performed by cost-minimization and reference price
      methodology. RESULTS: The consumption of antidepressants in Lithuanian increased
      by 30.55% over a 3-year period (2002-2004) reaching the value of 10.00 DDDs/1000
      inhabitants/day. Since 2002, the proportion of use of selective serotonin
      reuptake inhibitors has increased by 27.82%, and the use of tricyclic
      antidepressants has declined by 10.78%, while the use of other (newer)
      antidepressant drugs expanded almost three times. The expenditures of
      antidepressant drugs have reached 26 million Lt in 2004, of which 68.15% were
      costs for selective serotonin reuptake inhibitors. Choosing the second lowest
      price in different antidepressant drug class, it is estimated the possible
      savings of 4.34 million Lt lowering the total expenses by 16.5% (1 euro=3.4528
      Lt). CONCLUSIONS: The findings suggest that the use of total antidepressant drugs
      continues to increase because of the increased use of selective serotonin
      reuptake inhibitors and other (newer) antidepressant drugs. In comparison with
      the data in other countries, the consumption of antidepressant drugs in Lithuania
      is low.

PMID- 17211110
TI  - [Rational treatment of diabetes mellitus in Siauliai and Telsiai regions,
      Lithuania].
AB  - OBJECTIVE: The evaluation of adherence to guidelines on rationality in
      prescribing reimbursed medicines for the treatment of diabetes mellitus. MATERIAL
      AND METHODS: A retrospective evaluation of drug utilization in national public
      health insurance database and analysis of 906 case histories of diabetic patients
      in respect of nonadherence to guidelines. RESULTS: A total of 184 (20.3%) case
      histories with 370 events were found to be nonadherent to: a) national guidelines
      on prescription of medicines (66.49%); b) authorized indications and
      contraindications (13.24%); c) insufficient monitoring (4.32%); d) nonadherence
      to the recommendations for prescription writing (11.35%); and e) nonadherence to
      the requirements for service provisions (4.6%). The analysis of nonadherence to
      national guidelines revealed: 1) failure to assess patient's height, weight, and
      body mass index (30.1%); 2) poor glycemia control (26%); 3) failure in referring
      to an endocrinologist in case of noncontrolled glycemia (17.5%); 4) monotherapy
      with long-acting insulin or started combined oral therapy without monotherapy
      (10.2%); 5) noncompliance with the recommendations of endocrinologist (8.5%); 6)
      unsubstantiated changes in diabetes mellitus treatment (4.1%). Thiazolidinediones
      are often administered in case of liver failure or without investigation of its
      function (60.4%) or in case of heart failure (29.2%). CONCLUSIONS: 1)
      Nonadherence was observed in 20.3% of cases; 2) the most frequent cause was
      nonadherence to guidelines (66.5%) and to authorized indications and
      contraindications (13.2%); 3) thiazolidinediones were prescribed in the presence
      of the contraindications. The areas for intervention are: 1) more active
      monitoring of glycemia; 2) the assessment of height, weight, and body mass index;
      and 3) the prescription of thiazolidinediones according to authorized indications
      and contraindications.

PMID- 17211112
TI  - Determination of drug information needs of health care professionals in Estonia.
AB  - OBJECTIVE: To determine the current sources and perceived needs of drug
      information among Estonian physicians and pharmacists. METHODS. A survey was
      conducted among 2000 health care professionals subscribing to a drug information
      bulletin. The questionnaire addressed the most important areas of drug
      information for the respondent, the areas of drug information most difficult to
      access, the main sources of drug information currently used, the quality of
      information received from the representatives of drug manufacturers, and the need
      for an independent drug information center (DIC). RESULTS: A total of 457 (23%)
      questionnaires were returned. Of all the respondents, 82% were physicians and 18%
      -pharmacists. More than half of respondents (59%) had over 20 years, 30% had 10
      20, and 11% up to 10 years of professional experience. The most important areas
      of information identified by the respondents were pharmacological action,
      indications, dosing, and contraindications. The same were considered to be the
      most difficult areas to find data about. The main sources of drug information
      were datasheet compendium Pharmaca Estica, specialty handbooks, medical journals,
      and drug manufacturers' representatives. Manufacturers' representatives provided
      mainly data about pharmacological action, indications, and dosing (respectively,
      66, 64, and 58% of respondents always got this information). Most respondents
      (89%) considered the information from the manufacturers sufficient; 88% of
      respondents still considered a drug information center necessary. CONCLUSION: The
      most important areas of drug information (pharmacological action, indications,
      dosing, and contraindications), the areas difficult to access (medical questions
      of use in the elderly, drug interactions, use during pregnancy and lactation),
      the main sources of drug information (Pharmaca Estica, specialty handbooks,
      medical journals, etc.) and the most favored ways of getting information from the
      drug information center (by phone, by e-mail) were determined. There were limited
      differences in the opinions of different professionals and a very high proportion
      of respondents considered the drug information center necessary.

PMID- 17211113
TI  - [Breastfeeding and medications].
AB  - Breastfeeding is the most healthful method of feeding neonates and infants. In
      2001 about 98% of new mothers in Lithuania started breastfeeding their neonates.
      One-third of nursing women (34%) discontinued breastfeeding at the time when
      infant reached the age of 3 months. About 56% of women breastfed their infants
      longer than 4 months. Only 3-6% of nursing women discontinued breastfeeding after
      the fourth month. Discontinuation of breastfeeding in 21-23% of all cases was
      directly or indirectly associated with use of medications. Such data suggest that
      there is a lack of information often leading physicians to advise mothers to
      discontinue breastfeeding because of medication use. The aim of this article was
      to survey the situation about classification of drugs used during breastfeeding
      and factors influencing drug transfer into milk in order to give more information
      for physician concerning the use of medication during breastfeeding. In this
      review, a short description of main pharmacokinetic characteristics, influencing
      drug transfer into milk; information on the classification of drugs used during
      breastfeeding; some considerations on drug safety and possible adverse effects of
      medications on breastfed infant; the list of drugs preferred for nursing women
      are presented.

PMID- 17211114
TI  - [Effects of aerobic exercise using a flex-band on physical functions & body image
      in women undergoing radiation therapy after a mastectomy].
AB  - PURPOSE: This study examined the effects of aerobic exercise using a flex band on
      the improvement of physical functions & body image in breast cancer women
      undergoing radiation therapy after a mastectomy. METHOD: Women with breast
      cancer(n = 26) were assigned to an experimental group(EG, n = 15) and control
      group(CG, n = 11). The E.G. participated in an aerobic exercise program with a
      60% to 80% intensity of maximal heart rate for 25 minutes during the main
      exercise, 3 times per week, for 6 weeks. The EG did not exercise regularly for 3
      months before participating in this program. The CG received no exercise
      treatment during the research period. Data were analyzed using the chi(2)-test
      and Mann-Whitney U test by the SPSS version 11.0 program at a 5% significant
      level. RESULTS: Group analysis revealed that the EGwomen had significantly more
      improved cardiopulmonary functions, ROM of the affected shoulder joint, and body
      image compared to the CG. CONCLUSION: Aerobic exercise using a flex band may be
      an effective rehabilitative measure for mastectomy women with respect to cardio
      pulmonary functions, ROM, & body image. Further studies are recommended to study
      early rehabilitation programs within 10 days post-operatively.

PMID- 17211115
TI  - [The effects of the inhalation method using essential oils on blood pressure and
      stress responses of clients with essential hypertension].
AB  - PURPOSE: The purpose of this study was to identify the effects of aromatherapy on
      blood pressure and stress responses of clients with essential hypertension.
      METHOD: There were fifty-two subjects divided into an essential oil group,
      placebo group, and control group by random assignment. The application of
      aromatherapy was the inhalation method of blending oils with lavender,
      ylangylang, and bergamot once daily for 4 weeks. To evaluate the effects of
      aromatherapy, blood pressure and pulse were measured two times a week and serum
      cortisol levels, catecholamine levels, subjective stress, and state anxiety were
      measured before and after treatment in the three groups. Data was analyzed by
      repeated measures of ANOVA, one-way ANOVA, and chi(2)-test using the SPSS 10.0
      program. RESULTS: The blood pressure, pulse, subjective stress, state anxiety,
      and serum cortisol levels among the three groups were significantly statistically
      different. The differences of catecholamine among the three groups were not
      significant statistically. CONCLUSION: The results suggest that the inhalation
      method using essential oils can be considered an effective nursing intervention
      that reduces psychological stress responses and serum cortisol levels, as well as
      the blood pressure of clients with essential hypertension.

PMID- 17211116
TI  - [Effects of a structured drug education program on knowledge and medication
      compliance for hemodialysis patients].
AB  - PURPOSE: The purpose of this study was to analysis the effects of a structured
      drug education program on knowledge and medication compliance for hemodialysis
      patients. METHOD: Hemodialysis patients were recruited from a kidney center, at a
      university hospital located in G city, Korea. Thirty subjects in the control
      group received no intervention and 30 subjects in the experimental group received
      a structured drug education program. RESULT: There were significant increases in
      medication knowledge and medication compliance in the experimental group compared
      to the control group. CONCLUSION: According to the above results, this education
      program for hemodialysis patients increased knowledge and medication compliance.
      These findings suggest that a structured drug education program can be used as an
      efficient nursing intervention for hemodialysis patients.

PMID- 17211117
TI  - [Comparison of quality of life between kidney transplant and hemodialysis
      patients].
AB  - PURPOSE: The purpose of this study was to discover kidney transplant and
      hemodialysis patients' quality of life(QOL) and provide basic data to improve
      their QOL. METHOD: One hundred two hemodialysis patients and 106 kidney
      transplant patients were given a self-administered questionnaire from Mar. 6 to
      Mar. 31, 2006. The instrument consisted of demographic variables, therapeutic
      related characteristics and QOL. Collected data was processed using the SPSS 12.0
      statistical program for real numbers, percentages, ANCOVA, t-test, ANOVA,
      Stepwise multiple regression and the Scheffe test. RESULTS: Kidney
      transplantpatients' QOL was higher than hemodialysis patients. The demographic
      variables which showed a significant difference in overall QOL were religion,
      children and monthly income for kidney transplantpatients and educational
      background for hemodialysis patients. The therapeutic-related variable which
      showed a significant difference in overall QOL was the patients' perceived health
      condition for both groups. The influencing factor on overall QOL for both groups
      was the health condition perceived by themselves. The total variance of the
      variable for QOL was 42% for kidney transplant patients and 19% for hemodialysis
      patients. CONCLUSION: This study revealed that kidney transplant patients have a
      higher QOL and how patients perceive their health is the strongest influencing
      factor for QOL. However, there is a large difference between the demand and
      supply of kidney donors. To solve this problem the standards for donation should
      be reviewed and revised.

PMID- 17211118
TI  - [Development of E-Mail education for hyperlipidemia health check-up and
      application effects].
AB  - PURPOSE: This study was to monitor the effects of forming desirable eating and
      exercise habits and change the blood lipid levels by developing and applying E
      Mail educational programs for a hyperlipidemia health check-up. METHOD: The
      research design used a nonequivalent control group pre-post test. Ninety-nine
      subjects (Exp.=50, Cont.=49) were selected randomly and the male subjects agreed
      to a hyperlipidemia health check-up at a comprehensive medical screening center.
      This study verified validity and reliability through factor analysis on a life
      habit measurement tool. The data was analyzed with SPSS win 12.0 using an chi-
      square-test,t-test, ANOVA and ANCOVA. RESULT: Eatingand exercise habit scores of
      the experimental group which were educated through E-Mails changed considerably
      more than that of the control group which was not educated. Total-cholesterol and
      LDL-cholesterol in the experimental group was considerably lower than that in the
      control group, but HDL-cholesterol increased considerably. Triglycerides,
      however, didn't show change. CONCLUSION: An E-Mail educational program may be
      applied as a hyperlipidemia health check-up nursing intervention strategy.

PMID- 17211119
TI  - [The effects of a PMS nutritional education program for college students].
AB  - PURPOSE: This study was conducted to identify the effects of a PMS nutritional
      education program for college nursing students. METHOD: Subjects consisted of
      nursing students(experimental group: 29, control group: 27). The experimental
      group participated in a PMS nutritional education program for 8 weeks (including
      group and individual involvement). Data was collected before and after the
      education, and measurement tools were premenstrual symptoms, PMS knowledge, and
      self health behavior. RESULTS: After the intervention, the experimental group
      showed a significant increase in PMS knowledge(Z=6.32, p=.000) and self health
      behavior(t=3.00, p=.004) compared to the control group. After the intervention
      the experimental group showed a significant increase in PMS knowledge(Z=-4.64,
      p=.000) and self health behavior(t=-3.04, p=.005) than before the intervention.
      CONCLUSIONS: These results suggest that the short term effects of a PMS
      nutritional education program for nursing students was proven useful and the
      program should be applied to PMS nutrition education for PMS clients as well as
      health professionals.

PMID- 17211120
TI  - [Effects of education on knowledge and practice of caregivers of the stroke
      patient].
AB  - PURPOSE: This study was conducted to evaluate the effects of stroke patient care
      education on the knowledge and practice of caregivers of stroke patients. METHOD:
      Data was collected from December 15, 2004 to March 30, 2005. The research design
      was a non-equivalent control group non-synchronized design. The subjects were
      forty primary caregivers of stroke patients who were hospitalized in a neurology
      unit of a university hospital. Forty caregivers, twenty in the experimental group
      and twenty in the control group were assigned. The experimental group
      participated 2 times in an education class given by the researcher. Data analysis
      included -test, and t-test using the SPSS program. RESULT: Knowledge(t=5..87,
      p=o.oo) and practice(t=5.53, p=0.00) of the experimental group were significantly
      different from the control group. CONCLUSION: The stroke patient care education
      developed in this study shows a significant promotion of knowledge and practice
      of caregivers. Thus this program can be recommanded as an intervention model for
      stroke patients and caregivers.

PMID- 17211121
TI  - [A preliminary survey of nurses' understanding of delirium and their need for
      delirium education - in a university hospital -].
AB  - PURPOSE: The purpose of this survey was to investigate clinical nurses'
      understanding of delirium and their educational need of delirious patient care.
      METHOD: A survey questionnaire regarding nurses' general perception and
      understanding of delirium, experience with delirious patients and educational
      need was developed and conducted with 179 clinical nurses in a university
      hospital in Seoul. Data was analyzed using descriptive statistics. RESULTS:
      Nurses thought that delirium was one of the most important nursing problems and
      they considered it to be more treatable than to be preventable. However, the
      majority of nurses were not confident in caring for delirious patients. Nurses
      reported that delirium happened most often after surgery, and that possible
      contributing factors could be changes in physical environment and anxiety/stress,
      as well as medication and long-term isolation. Thirteen nursing interventions
      were identified but half of the nurses utilized only one or two of the thirteen.
      The most frequently used intervention was reorienting the patient followed by
      medication and emotional support, presenting family, and close observation. 99.5%
      of nurses addressed the importance of professional education on delirium care,
      especially in the area of intervention and management. CONCLUSION: The results
      support the strong need for development of a multi-component educational program
      on delirium care.

PMID- 17211122
TI  - [Current status of costs and utilizations of hospital based home health nursing
      care in Korea].
AB  - PURPOSE: The purpose of this study was to describe the current status of
      utilization and costs of home health nursing care by the levels of medical
      institutes in Korea. METHOD: A secondary analysis of existing data was used from
      the national electronic data information(EDI) of 148 home health agencies for 6
      months from May to Oct 2005 in total. RESULT: The 148 agencies had multiple
      services in cerebral infaction, essential hypertension, sequela of
      cerebrovascular disease, type 2 diabetes mellitus, etc.. The highest 10 rankings
      of 76 categories of home health nursing services were composed of 96.4% of the
      total services, such as simple treatment, inflammatory treatment, urethra &
      bladder irrigation, inserting indwelling catheter etc., in that order. The
      highest 20 rankings of 226 categories of home examination services were composed
      of 77.0% of the total home examination services. In addition, the average cost of
      home health care per visit was 46,088 Won ( approximately 48 $, 1 $=960 Won). The
      costs ranged from 74,523 Won ( approximately 78 $, loss of chronic kidney
      function, N18) to 32,270 Won ( approximately 34 $, other cerebrovascular
      diseases, I67). CONCLUSION: Results suggest that client characteristics of
      hospital based HHNC are not different from community based HHNC or visiting
      nursing services for elderly. The national results will contribute to baseline
      data used to establish a policy for the home health nursing care system and
      education.

PMID- 17211124
TI  - [Experiences of being tied with drugs in the elderly women in community].
AB  - PURPOSE: This study was done to understand elderly women within a community who
      have used lots of drugs. METHOD: Data was collected through in-depth interviews
      with four elderly women from April 2001 to February 2002. Data was analyzed by
      Giorgi's phenomenological method(2000). RESULTS: The components in common with
      drug usage of elderly women were as follows: 'Awareness of the limitation of
      physical strength and uncertainty of life', 'Dread of a crisis situation
      occurring', 'Attachment and dependency on drugs', 'Expectation of a comfortable
      life and death', 'Prevention of family burden', and 'Pursuit of psychological
      comfort'. The general structure of experiences was as follows: causal factors
      were 'Awareness of uncertainty and limitation', 'dread of a crisis situation
      occurring' the results factor was 'Attachment and dependency on drugs' and the
      facilitating factors were 'Expectation of a comfortable life and death',
      'Prevention of family burden', and 'Pursuit of psychological comfort'. The causal
      relation was cyclic. This structure showed a realistic adaptation pattern.
      CONCLUSION: This study contributed to provide fundamental data for nursing
      interventions for health promotion and promoting quality of life in elderly women
      by increasing understanding of the experiences of drugs use.

PMID- 17211123
TI  - [Status of nosocomial urinary tract infections in the ICU: molecular epidemiology
      of imipenem resistant P. aeruginosa].
AB  - PURPOSE: This retrospective study was done to evaluate the status of nosocomial
      urinary tract infections and to determine the risk factors and transmission route
      of causal IRPA through molecular epidemiology. METHOD: Two hundred ninety-nine of
      423 patients admitted to the internal medicine and surgery ICU at a university
      hospital incity B had a positive urine culture. Twelve of the 299 patients who
      had a urinary tract infection had IRPA strains. The data was collected from
      November 1, 2004 to January 31, 2005. The following results were obtained after
      the data was analyzed using percentile and UPGMA. RESULT: The rate of nosocomial
      urinary tract infections in the ICU was 10.8%. There were 16.8 cases of infection
      based on the period of hospitalization. There were 16.9 cases of infection based
      on the use of a foley catheter. The rate of nosocomial urinary tract infection in
      the ICU and urinary tract infections related to IRPA were higher in patients with
      the following characteristics: men, old age, admission through the emergency
      room, longer than seven days admission, severity of admitting causes, disturbance
      of consciousness, hydration less than 300 cc in 24 hours, a long course of
      antibiotics, a long period of foley catheterization and perineal care. Most of
      the microorganisms that caused the urinary tract infection were gram negative
      bacilli, among which P. aeruginosa was found in 70 patients (18.5%) and IRPA in
      12 (4.0%). Among the 12 IRPA strains that were tested with PFGE, eight showed a
      dice coefficient higher than 80%, suggesting a genetic relationship. They were
      related with the period of hospitalization in the same ICU. These patients all
      received direct care for a urinary tract infection. CONCLUSION: Through these
      results, IRPA can be considered as a contributing factors to urinary tract
      infections thus, active preventative measures are needed by the medical staff.

PMID- 17211125
TI  - [Comprehensive predictors of fatigue for cancer patients].
AB  - PURPOSE: This study was conducted to identify comprehensive predictors of fatigue
      in cancer patients. METHODS: One hundred ten cancer patients visiting in-patient
      or out-patient clinics of a university hospital located in Incheon participated
      in this study. RESULTS: The hematologic indicators (WBC and Hemoglobin) were
      significant for explaining fatigue. The psychological factors of fatigue were
      statistically significant. Both anxiety and depression, included as psychological
      factors, were significant in explaining fatigue in cancer patients. The influence
      of physical factors on fatigue was also statistically significant. Among the
      variables included as physical factors, pain, nausea/vomiting/anorexia, and sleep
      disturbance were significant whereas, dyspnea was not significant. The influence
      of the daily activity factor on fatigue was statistically significant. Among the
      variables included as daily activity factors, regular exercise or not and the
      usual activity level were significant in explaining fatigue of cancer patients,
      while the level of rest was not statistically significant. CONCLUSIONS: From the
      study results fatigue of cancer patients appeared to be influenced by
      multidimensional factors, such as physiological, physical, psychological, and
      activity related factors.

PMID- 17211126
TI  - [Effects of isometric contraction training by electrostimulation on Type I and II
      hindlimb muscles in cerebral ischemia model rats].
AB  - PURPOSE: The purpose of this study was to examine the effects of cerebral
      ischemia on Type I(soleus) and Type II(plantaris, gastrocnemius) muscles, and to
      determine the effects of isometric contraction training by electrostimulation on
      Type I and II muscles in cerebral ischemia model rats. METHOD: Twenty-five male
      Sprague-Dawley rats were randomly divided into four groups: ST(stroke),
      STES(stroke+electrostimulation), SH(sham) and SHES (sham+electrostimulation). The
      ST and STES groups received a transient right middle cerebral artery occlusion
      operation. The SH and SHES groups received a sham operation. The STES and SHES
      groups had daily isometric contraction training by electrostimulation(100 Hz, 45
      mA, 7.5 V) on hindlimb muscles for 7 days. RESULT: Plantaris and gastrocenmius
      muscle weight, myofibrillar protein contents of soleus and gastrocnemius, and the
      muscle fiber cross-sectional area of gastrocnemius in the ST group significantly
      decreased compared with the SH group. Soleus, plantaris, gastrocnemius muscle
      weight, myofibrillar protein contents of soleus and gastrocnemius, and the Type I
      muscle fiber cross-sectional area of soleus and the Type II muscle fiber cross
      sectional area of gastrocnemius in the STES group significantly increased
      compared with the ST group. CONCLUSION: Hindlimb muscle atrophy occurs after
      acute stroke and isometric contraction training by electrostimulation during
      early stages of a stroke attenuates muscle atrophy of Type I and Type II muscles.

PMID- 17211127
TI  - [The attitudes of nurses toward transsexuals].
AB  - PURPOSE: The purpose of this study was to identify the attitude of nurses toward
      transsexuals. METHOD: The Q-methodology which provides a method of analyzing the
      subjectivity of each item was used. Twenty-nine nurses classified the 50 selected
      Q-statements into a normal distribution using a 9 point scale. The collected data
      was analyzed using the Quanl PC program. RESULT: Four types of attitudes toward
      transsexuals were identified. The first type (humanitarian acceptance) showed an
      attitude of respecting transsexuals as human beings and understanding and
      accepting their desires and difficulties. The second type (superficial
      understanding) understood the psychological conflicts and suffering of
      transsexuals but could not accept them as members of families or society. The
      third type (insufficient understanding) did not feel a sense of rejection toward
      transsexuals but showed a lack of understanding of their desires and
      difficulties. The fourth type (rejection) failed to understand the desires and
      difficulties of transsexuals and showed a sense of rejection toward them, in
      addition to regarding them as sexually immoral people. CONCLUSION: The results of
      the study indicate that different approaches of educational programs based on the
      four types of attitudes toward transsexuals are recommended.

PMID- 17211128
TI  - [A conversation analysis of communication between patients with dementia and
      their professional nurses].
AB  - PURPOSE: The purpose of this study was to understand conversations and to
      identify typical conversational problems between nurses and patients with
      dementia. METHOD: A conversation analysis method was used. The data was collected
      in a geriatric institutional setting, using a videotape recorder, and
      transcribed. The transcribed data was analyzed in terms of expressions, contents,
      and relationships to identify communicative problems and their resolutions.
      RESULTS: Among a total of 532 episodes, 440(82.7%) were identified as nurse
      involved episodes. In addition, 66 of the 440 episodes were selected based on the
      significance of the conversation. The communicative problems between nurses and
      patients in terms of expressions were identified as "directive and authoritative
      expressions", "emotional and competitive expressions", "evasive and on-looking
      expressions", and "excessive use of title only", such as calling them granny or
      grandpa without proper names. In terms of content and relationships, "lack of
      themes in psychosocial areas" and "nurse-led relations" were identified
      respectively as communicative problems. CONCLUSION: The results of this study
      will provide substantial guidelines for nurses in caring for elderly patients
      with dementia by deeply understanding linguistic structures and problems of
      everyday conversations between nurses and patients with dementia.

PMID- 17211129
TI  - [Evaluation of a virtual class on lifelong health care for women].
AB  - PURPOSE: This study was to evaluate a virtual class, 'lifelong health care for
      women', for female university students. METHOD: The research design was one group
      pre-post design. A pretest and posttest were conducted to measure CMI, perceived
      health status, health promoting lifestyle, and knowledge related to women's
      health. The subjects of this study were 74 female students in 3 universities, and
      they were provided with the virtual class by K university consortium for 16
      weeks. Data was analyzed by descriptive and paired t-test. RESULTS: There were
      statistically significant differences in CMI (t=3.367, p=.001), perceived health
      status (t=-2.788, p=.007), and knowledge related to women's health (t=-10,432,
      p=.000) between the pretest and posttest. However, there was not a statistically
      significant difference in a health promoting lifestyle (t=-1.431, p=.157) between
      the pretest and posttest. CONCLUSION: These results suggest that a virtual class
      on lifelong health care for women is an effective method in decreasing health
      problems, and improving perceived health status and knowledge related to women's
      health by female university students.

PMID- 17211132
TI  - Protection of the neonate by the innate immune system of developing gut and of
      human milk.
AB  - The neonatal adaptive immune system, relatively naive to foreign antigens,
      requires synergy with the innate immune system to protect the intestine. Goblet
      cells provide mucins, Paneth cells produce antimicrobial peptides, and dendritic
      cells (DCs) present luminal antigens. Intracellular signaling by Toll-like
      receptors (TLRs) elicits chemokines and cytokines that modulate inflammation.
      Enteric neurons and lymphocytes provide paracrine and endocrine signaling.
      However, full protection requires human milk. Breast-feeding reduces enteric
      infection and may reduce chronic disease in later life. Although human milk
      contains significant secretory immunoglobulin A (sIgA), most of its protective
      factors are constitutively expressed. Multifunctional milk components are
      nutrients whose partial digestion products inhibit pathogens. Cytokines, cytokine
      receptors, TLR agonists and antagonists, hormones, anti-inflammatory agents, and
      nucleotides in milk modulate inflammation. Human milk is rich in glycans (complex
      carbohydrates): As prebiotics, indigestible glycans stimulate colonization by
      probiotic organisms, modulating mucosal immunity and protecting against
      pathogens. Through structural homology to intestinal cell surface receptors,
      glycans inhibit pathogen binding, the essential first step of pathogenesis.
      Bioactive milk components comprise an innate immune system of human milk whereby
      the mother protects her nursing infant. Interactions between human milk glycans,
      intestinal microflora, and intestinal mucosa surface glycans underlie ontogeny of
      innate mucosal immunity, pathobiology of enteric infection, and inflammatory
      bowel diseases.

PMID- 17211133
TI  - Comparison of two neonatal ischemic injury models using magnetic resonance
      imaging.
AB  - Using an 11.7-Tesla magnetic resonance imaging (MRI) scanner in 10-d-old rat pups
      we report on the evolution of injury over 28 d in a model of neonatal stroke
      (transient filament middle cerebral artery occlusion, tfMCAO) and a model of
      hypoxic-ischemic injury (Rice-Vannucci model, RVM). In both models, diffusion
      weighted imaging (DWI) was more sensitive in the early detection of ischemia than
      T2-weighted imaging (T2WI). Injury volumes in both models were greater on d 1 for
      DWI and d 3 for T2WI, decreased over time and by d 28 T2WI injury volumes (tfMCAO
      10.3% of ipsilateral hemisphere; RVM 23.9%) were definable. The distribution of
      injury with tfMCAO was confined to the vascular territory of the middle cerebral
      artery and a definable core and penumbra evolved over time. Ischemic injury in
      the RVM was more generalized and greater in cortical regions. Contralateral
      hemispheric involvement was only observed in the RVM. Our findings demonstrate
      that high-field MRI over extended periods of time is possible in a small animal
      model of neonatal brain injury and that the tfMCAO model should be used for
      studies of neonatal stroke and that the RVM does not reflect the vascular
      distribution of injury seen with focal ischemia.

PMID- 17211134
TI  - Toll-like receptor ligands and CD154 stimulate microglia to produce a factor(s)
      that promotes excess cholinergic differentiation in the developing rat basal
      forebrain: implications for neurodevelopmental disorders.
AB  - Maternal inflammation plays a role in the etiology of certain neurodevelopmental
      disorders including autism and schizophrenia. Because maternal inflammation can
      lead to activation of fetal microglia, we have examined effects of inflamed
      microglia on cultured neural progenitors from rat embryonic septal region and
      basal forebrain. These cells give rise to cholinergic neurons projecting to
      cortex and hippocampus. Microglia stimulated with lipopolysaccharide (LPS),
      peptidoglycan, Poly I:C and CD154 produce conditioned media (CM) that promotes
      excessive numbers of cholinergic neurons and levels of choline acetyltransferase
      (ChAT) activity 6-8 times that of untreated cultures. Expression of the neural
      specific transcription factor MATH1 increases substantially within 1 h of plating
      in LPS-CM. Untreated cultures do not attain equivalent levels until 6 h. By
      contrast, expression of glial-related transcription factors in LPS-CM-treated
      cultures never attains the elevated levels of untreated cultures. LPS-CM-treated
      clones derived from individual progenitors labeled with a LacZ-expressing
      retrovirus showed >2.5-fold increase in the percentage of cholinergic cells
      compared with untreated clones. Thus, CM from activated microglia prompts excess
      cholinergic differentiation from undifferentiated progenitors suggesting that
      microglial inflammation during critical stages can lead to aberrant brain
      development.

PMID- 17211135
TI  - Lung deposition of HFA beclomethasone dipropionate in an animal model of
      bronchopulmonary dysplasia.
AB  - The best delivery of a drug in ventilated neonates is obtained when using a small
      particle diameter solution administered via a spacer. Lung deposition of
      hydrofluoroalkane beclomethasone dipropionate (QVAR, 1.3 microm particles),
      delivered via an Aerochamber-MV15, was measured in piglets under conditions
      mimicking ventilated severely ill neonates (uncuffed 2.5 mm endotracheal tube;
      peak pressure 16 cm H2O; respiratory rate 40/min). After determining the mass and
      particle size distribution of the 99mTc-labeled and unlabeled drug, three lung
      deposition studies were performed: after 1 h of ventilation (controls, n = 18),
      after 48 h aggressive ventilation inducing an acute lung injury (nine piglets out
      of the controls), and after increasing the pressure to 24 cm H2O during drug
      delivery (five piglets out of the nine with acute lung injury). All piglets were
      then killed for lung histology. Results (median, range), expressed as a
      percentage of the delivered dose, were compared using an inferential or the
      Friedman test. While lung deposition was low, it was greater (p = 0.003) in
      controls (2.66%, 0.50-7.70) than in piglets with histologically confirmed acute
      lung injury (0.26%, 0.06-1.28) or under a high-pressure ventilation (1.01%, 0.30
      2.15). Lung deposition of QVAR in an animal model of ventilated neonates is low,
      variable, and dramatically affected by lung injury.

PMID- 17211136
TI  - Cathepsin-G interferes with clearance of Pseudomonas aeruginosa from mouse lungs.
AB  - The cystic fibrosis airway is susceptible to Pseudomonas aeruginosa infection,
      which stimulates an intense inflammatory response leading to airway obstruction
      and bronchiectasis. Neutrophils migrate into the airway, and once there, release
      high concentrations of neutral serine proteases during phagocytosis and in death.
      In particular, neutrophil elastase is central to progression of bronchiectasis by
      interfering with bacterial clearance and directly perpetuating the inflammatory
      response in the airway. Using a murine model of endobronchial inflammation, we
      found that a different neutrophil-derived serine protease, cathepsin G, inhibited
      the host's ability to clear Pseudomonas from the lung, based on a 1-log reduction
      in bacteria recovered from cathepsin G-deficient mice. Higher antibody
      concentrations were found in respiratory epithelial lining fluid from mice
      lacking cathepsin G, but there was no difference in other opsonins, such as
      surfactant proteins A and D. Chemokine levels measured in the lung correlated
      with bacterial burden and not the animal's genotype, indicating that airway
      inflammation was not affected by the presence (or absence) of specific serine
      proteases. These findings suggest that cathepsin G interferes with airway
      defenses, showing that proteases other than neutrophil elastase have roles in the
      pathogenesis of suppurative airway diseases.

PMID- 17211137
TI  - Fibroblast growth factor-2 expression is altered in lambs with increased
      pulmonary blood flow and pulmonary hypertension.
AB  - A lamb model of pulmonary hypertension, developed by inserting an aortopulmonary
      vascular graft (shunt), displays vascular remodeling and increased pulmonary
      blood flow characteristic of children with congenital heart disease. The purpose
      of this study was to determine whether expression of fibroblast growth factor-2
      (FGF-2), a smooth muscle cell mitogen, is altered in shunt lambs. FGF-2 mRNA and
      protein levels were increased in lung tissue extracts from shunt lambs at 4 wk of
      age relative to age-matched controls (p < 0.05). FGF-2 protein levels were also
      increased in the pulmonary arteries and serum of shunt lambs (p < 0.05).
      Pulmonary arterial smooth muscle cells (PASMC) and endothelial cells (PAEC) were
      isolated from 4 wk-old lambs and subjected to cyclic stretch and laminar shear
      stress to mimic increased pulmonary blood flow. Stretch and shear increased FGF-2
      promoter activity, and intracellular and extracellular FGF-2 protein levels in
      both cell types (p < 0.05). Exogenous FGF-2 stimulated PASMC proliferation at
      levels detected in the extracellular medium of sheared cells (p < 0.05). Elevated
      FGF-2 signaling by PASMC and PAEC exposed to increased pulmonary blood flow may
      play a role in the pulmonary vascular remodeling associated with the shunt model
      of pulmonary hypertension secondary to congenital heart disease.

PMID- 17211138
TI  - Effects of butyrate on intestinal barrier function in a Caco-2 cell monolayer
      model of intestinal barrier.
AB  - Production of short-chain fatty acids (SCFA) in the intestinal lumen may play an
      important role in the maintenance of the intestinal barrier. However,
      overproduction/accumulation of SCFA in the bowel may be toxic to the intestinal
      mucosa and has been hypothesized to play a role in the pathogenesis of neonatal
      necrotizing enterocolitis (NEC). By using a Caco-2 cell monolayer model of
      intestinal barrier, we report here that the effect of butyrate on the intestinal
      barrier is paradoxical. Butyrate at a low concentration (2 mM) promotes
      intestinal barrier function as measured by a significant increase in
      transepithelial electrical resistance (TER) and a significant decrease in inulin
      permeability. Butyrate at a high concentration (8 mM) reduces TER and increases
      inulin permeability significantly. Butyrate induces apoptosis and reduces the
      number of viable Caco-2 cells in a dose-dependent manner. Intestinal barrier
      function impairment induced by high concentrations of butyrate is most likely
      related to butyrate-induced cytotoxicity due to apoptosis. We conclude that the
      effect of butyrate on the intestinal barrier is paradoxical; i.e. whereas low
      concentrations of butyrate may be beneficial in promoting intestinal barrier
      function, excessive butyrate may induce severe intestinal epithelial cell
      apoptosis and disrupt intestinal barrier.

PMID- 17211139
TI  - Nutrient restriction impairs nephrogenesis in a gender-specific manner in the
      ovine fetus.
AB  - Inadequate nutrition compromises fetal development and poses long-term health
      risks for the offspring, even without decreased birth weight. The present study
      sought to 1) establish the ontogeny of fetal renal glomerulus number (GN) in
      sheep and 2) evaluate the effects of 50% global nutrient restriction (NR) during
      early to midgestation on GN and the renin-angiotensin system in the fetal kidney.
      GN increased from 78 dG (68,560 +/- 3802) to 135 dG (586,118 +/- 25,792). NR
      increased combined kidney weight (29 +/- 0.6 g versus 23 +/- 1.1 g), whereas
      decreased GN relative to right kidney weight approached significance in males
      (26,000 +/- 5300 versus 39,000 +/- 2800 GN/g) compared with control (C) males and
      females. NR decreased immunoreactive angiotensin II (Ang II) type 1 receptor
      (AT1) in the NR kidneys at 78 dG and increased renin at 135 dG. Immunoreactive
      renin decreased from 78 to 135 dG. Female fetuses had more immunoreactive Ang II
      type 2 receptor (AT2) than male fetuses at 78 dG and males had more AT1 at 135
      dG. The present study demonstrates gender-specific differences in fetal growth
      and development and in fetal kidney development in pregnancies affected by NR.

PMID- 17211140
TI  - Effect of neonatal exposure to genistein on bone metabolism in mice at adulthood.
AB  - Infants fed soy-based infant formulas are exposed to high levels of genistein, an
      isoflavone, with potential estrogen-like activity. This study determined whether
      neonatal exposure of mice to genistein resulted in higher bone mineral density
      (BMD) and greater resistance to fracture at adulthood. Male and female CD-1 mice
      (n = 4-14/group) were randomized to control (CON) (corn oil, s.c.),
      diethylstilbestrol (DES) (2 microg/pup/d, s.c.), or genistein (GEN) (4
      microg/pup/d, s.c.) from d 1 through 5 of life. At 21 d of age, pups were weaned
      and studied until 4 mo of age when tissues were collected. Among females, femur
      (p = 0.016) and lumbar vertebrae (LV1-LV4) (p < 0.001) BMD were higher among DES
      and GEN groups compared with CON group. Importantly, the higher LV1-LV4 BMD was
      associated with stronger vertebrae that were more resistant to fracture as the
      peak load of LV3 (p = 0.012) was higher in the GEN and DES groups compared with
      CON group. In males, DES and GEN had divergent effects on femur and lumbar
      vertebrae BMD and peak load. In conclusion, early exposure to GEN has positive
      effects on femur and lumbar spine of females, likely due to estrogenic effects,
      while only the lumbar spine of males benefits from early exposure to GEN.

PMID- 17211141
TI  - Cortical consequences of in vivo blockade of monocarboxylate transport during
      brain development in mice.
AB  - In addition to glucose, monocarboxylates including lactate represent a major
      source of energy for the developing brain and appears to be crucial in the
      pathogenesis and recovery after brain damage. We hypothesized a role of
      monocarboxylates transport in the energy supply of neurons of the immature
      cerebral cortex. The effects of the blockade of monocarboxylates transport in
      vivo on the cortical development was investigated in neonatal mice using alpha
      cyano-4-hydroxycinnamate (CIN) diluted either in DMSO (CD) or in ethanol (CE)
      administered intraperitoneally over postnatal day (P) P1 to P3. Injection of CIN
      induced a cytoarchitectonic disorganization in the parietal cortex likely due to
      a combination of slight disturbance of cortical neuronal migration and an
      increased neuronal cell death observed in CE (p < 0.05) but not in CD group. An
      increased number of activated GFAP-positive astroglia was observed in the
      neocortex in groups treated with CIN (CD and CE) on P10. These data: 1) Provide
      first evidence of deleterious effects observed in vivo after blockade of
      monocarboxylates transport in the developing brain; 2) emphasize the role of
      lactate during neuronal migration as a major source of energy; and 3) suggest the
      synergistic effect of ethanol-induced hypoglycemia in cortical brain damage
      induced by CIN.

PMID- 17211142
TI  - Human meconium contains significant amounts of alkaline sphingomyelinase, neutral
      ceramidase, and sphingolipid metabolites.
AB  - Intestinal alkaline sphingomyelinase (Alk-SMase) and neutral ceramidase may
      catalyze the hydrolysis of endogenous sphingomyelin (SM) and milk SM in human
      milk fed infants. The enzymes generate sphingolipid metabolites that may
      influence gut maturation. Alk-SMase also inactivates platelet-activating factor
      (PAF) that is involved in the pathogenesis of necrotizing enterocolitis (NEC). We
      examined whether the two enzymes are expressed in both preterm and term infants
      and analyzed Alk-SMase, neutral ceramidase, SM, and sphingolipid metabolites in
      meconium. Meconium was collected from 46 preterm (gestational ages 23-36 wk) and
      38 term infants (gestational ages 37-42 wk) and analyzed for Alk-SMase using C
      choline-labeled SM and for neutral ceramidase using C-octanoyl-sphingosine as
      substrates. Molecular species of SM, ceramide, and sphingosine were analyzed by
      high-performance liquid chromatography mass spectroscopy. Meconium contained
      significant levels of Alk-SMase and ceramidase at all gestational ages. It also
      contained 16-24 carbon molecular species of SM, palmitoyl- and stearoyl
      sphingosine, and sphingosine. There were positive correlations between levels of
      SM and ceramide and between ceramide and sphingosine levels. In conclusion, Alk
      SMase and ceramidase are expressed in the gut of both preterm and term newborn
      infants and may generate bioactive sphingolipid messengers.

PMID- 17211143
TI  - A decapeptide from durum wheat prevents celiac peripheral blood lymphocytes from
      activation by gliadin peptides.
AB  - Identifying antagonist peptides able to inhibit the abnormal immune response
      triggered by gliadin peptides in celiac disease (CD) is an alternative
      therapeutic strategy for CD. The aim of this study was to evaluate the antagonist
      effect of 10mer, a decapeptide (sequence QQPQDAVQPF) from alcohol-soluble protein
      fraction of durum wheat, assessing its ability to prevent celiac peripheral blood
      lymphocytes from activation by gliadin peptides. Peripheral blood mononuclear
      cells (PBMC) were obtained from DQ2-positive untreated coeliac children and from
      healthy controls and incubated with the peptic-tryptic digest of bread wheat
      gliadin (GLP) and peptide 62-75 from alpha-gliadin both alone and with 10mer
      simultaneously. PBMC proliferation, release of pro-inflammatory Th1 cytokines
      interferon-gamma and tumor necrosis factor-alpha, release of immunoregulatory
      cytokine IL-10, and analysis of CD25 expression as indexes of lymphocytes
      activation were carried out. Enhanced lymphocytes activation was seen after
      exposure to GLP and p62-75, whereas the simultaneous incubation with 10mer
      inhibits the lymphocytes response. These data indicate that a peptide naturally
      occurring in durum wheat exerts in vitro an antagonist effect against gliadin
      toxicity and could have a protective effect in CD disease.

PMID- 17211144
TI  - Reduced life expectancy in rats after neonatal dexamethasone treatment.
AB  - The glucocorticoid dexamethasone (Dex) is widely used in preterm infants for the
      prevention of chronic lung disease. However, major concern has arisen about the
      long-term sequelae of this therapy. Here we report that neonatal treatment with
      dexamethasone significantly shortens the lifespan by 25% of male rats (28.6 +/-
      1.1 to 21.3 +/- 0.8 mo) and by 18% of female rats (26.9 +/- 1.8 to 22.0 +/- 0.7
      mo). Histopathological examination indicated end-stage cardiac and renal failure
      as the cause of premature death. Furthermore, Dex-treated rats showed symptoms of
      hypertension at young adult age, which worsened with increasing age. Thus, a
      brief period of glucocorticoid treatment during early life results in untimely
      death presumably due to cardiovascular and renal disease later in life. These
      serious, adverse long-term consequences call for prudence with glucocorticoid
      treatment of human preterm infants and careful follow-up of young adults with a
      history of neonatal glucocorticoid treatment.

PMID- 17211145
TI  - Electrical potential difference across the nasal epithelium is reduced in
      premature infants with chronic lung disease but is not associated with lower
      airway inflammation.
AB  - Airway liquid content and insufficient absorptive airway ion transport at birth
      are potentially important factors in the development and severity of neonatal
      respiratory disease. The role of deficient absorptive airway ion transport in the
      development of chronic lung disease of prematurity is unknown. Additionally, lung
      inflammatory mediators modulate airway ion transport. Their effect on preterm
      lung ion transport and absorptive capacity is not established. We performed
      serial nasal potential difference studies and broncho-alveolar lavage in preterm
      infants born less than 30 wk postmenstrual age over the first four postnatal
      weeks. Our study aims were to: 1) compare nasal potential difference between
      preterm infants developing chronic lung disease and babies of similar gestation
      who do not; and 2) examine for an association between airway inflammation and ion
      transport parameters. We found that potential difference across the nasal
      epithelium increased with gestation, remained low and unchanged in infants
      developing chronic lung disease over the first four postnatal weeks, was
      significantly lower at four weeks in chronic lung disease infants, and was not
      associated with lower airway inflammation at any time point. We conclude that
      infants with chronic lung disease postnatally have a persistently reduced
      absorptive airway ion transport capacity.

PMID- 17211146
TI  - Quantitative and qualitative study of gastric lipolysis in premature infants: do
      MCT-enriched infant formulas improve fat digestion?
AB  - Intragastric fat digestion was investigated by analyzing the products of
      lipolysis and the gastric lipase (HGL) levels of premature infants fed with a
      formula enriched with medium chain triglycerides (MCT) and those of infants fed
      with human milk. Infants were fed using a gastric tube and the gastric contents
      were aspirated twice a day for 5 d, before and at various times after gavage
      feeding. HGL levels were measured using the pHstat technique. After extraction,
      lipids were separated and quantified using thin-layer chromatography coupled to a
      flame ionization detector. Fatty acid methyl esters were analyzed by gas
      chromatography. HGL concentration increased during digestion, reaching 77.4 +/-
      43.1 microg/mL (around 75% of those recorded in adults). Mean HGL output was 115
      +/- 43 microg for 3 h and the overall intragastric lipolysis was 6.1 +/- 2.6%.
      Although the formula was enriched with octanoic and decanoic acid, the main fatty
      acids released in the stomach were palmitic (C16:0, 17.03 +/- 0.23% wt/wt) and
      oleic (C18:1 n-9, 28.23 +/- 1.26% wt/wt) acid. Similar results were obtained with
      infants fed with human milk. MCT supplementation has no quantitative or
      qualitative effects on the intragastric lipolysis, which is not higher in
      premature infant than in adults.

PMID- 17211148
TI  - IP-10 is an early diagnostic marker for identification of late-onset bacterial
      infection in preterm infants.
AB  - Very low birth weight (VLBW) infants with suspected late-onset infection
      requiring sepsis screening were enrolled in a prospective study to evaluate the
      diagnostic utilities of a comprehensive panel of key chemokines and cytokines,
      both individually and in combination, to identify diagnostic markers for early
      recognition of bacterial sepsis and necrotizing enterocolitis (NEC). Plasma
      chemokines interleukin (IL)-8, interferon-gamma-inducible protein 10 (IP-10),
      monokine induced by interferon-gamma (MIG), monocyte chemoattractant protein 1
      (MCP-1), growth-related oncogene-alpha (GRO-alpha), and regulated upon activation
      of normal T cell expressed and secreted (RANTES) and cytokines IL-1beta, IL-6, IL
      10, IL-12p70, and tumor necrosis factor alpha (TNF-alpha) were measured at the
      onset of sepsis (0 h) and 24 h later. Of 155 suspected infection episodes, 44
      were classified as infected. Concentrations of all studied inflammatory mediators
      (except IL-1beta and RANTES) were significantly higher in the infected than in
      the noninfected group at 0 h, but the levels decreased precipitously by 24 h. IP
      10 with a plasma cutoff concentration > or = 1250 pg/mL could identify all
      septicemic and NEC cases and had the highest overall sensitivity (93%) and
      specificity (89%) at 0 h. We conclude that preterm infants have the ability to
      induce a robust chemokine and cytokine response during sepsis, and IP-10 is a
      sensitive early marker of infection.

PMID- 17211147
TI  - Effects of iron-unsaturated human lactoferrin on hydrogen peroxide-induced
      oxidative damage in intestinal epithelial cells.
AB  - Human milk (HM) contains various bioactive antioxidants. Lactoferrin (Lf) has
      been assumed to be one of the major antioxidants in HM. We examined the
      antioxidative properties of iron-unsaturated human Lf (apo-hLf, the major form of
      Lf in HM) in two intestinal epithelial cell lines: (1) An intestinal epithelial
      cell line (IEC-6) were preincubated for 24 h with either 50 microg/mL of apo-hLf,
      iron-saturated human Lf (holo-hLf), iron-unsaturated bovine transferrin (apo
      bTf), or 800 ng/mL of the iron-chelating compound deferoxamine (DFX), followed by
      hydrogen peroxide (H2O2) challenge to induce oxidative stress. Survival rates
      were significantly higher in the cells preincubated with apo-hLf and DFX than
      those preincubated with holo-hLf. (2) Caco-2 cells were preincubated with or
      without apo-hLf for 24 h, followed by an H2O2 challenge. Intracellular oxidative
      stress was assessed by a fluorescent probe, 2',7'-dichlorodihydrofluorescein
      diacetate (DCF-DA). Fluorescent intensity of cell images and cell homogenates was
      significantly lower in the cells preincubated with apo-hLF than those
      preincubated without apo-hLF. Our study indicates that apo-hLf alleviates H2O2
      induced oxidative damage in intestinal cells due to the iron-chelating capacity.
      Therefore, Lf in HM may act as an antioxidant in the gastrointestinal tract
      (GIT).

PMID- 17211149
TI  - The contributions of plasma IGF-I, IGFBP-3 and leptin to growth in extremely
      premature infants during the first two years.
AB  - We determined the contributions of IGF-I, IGFBP-3 and leptin to growth in
      extremely premature infants over the first two years. Weight (Wt), crown-to heel
      length (CHL), plasma IGF-I, IGFBP-3 and leptin were measured in infants
      (gestation 24-33 wk) at birth (n = 54), expected date of delivery (EDD) and 6, 12
      and 24 mo post-EDD (n = 29). Area under the curve (AUC) for hormone levels was
      calculated over 4 periods: birth-EDD, EDD-200 d, EDD-350 d and EDD-700 d. IGFBP
      3, but not IGF-I or leptin, on day 1 correlated with birth Wt SD scores (SDS) (r
      = 0.46, p = 0.002) and CHL SDS (r = 0.41, p = 0.01). Wt SDS at EDD correlated
      with AUC IGF-I, IGFBP-3 and leptin (birth-EDD), but leptin was the best predictor
      in multiple regression (r = 0.65, p < 0.0001). Wt at EDD + 700 d correlated with
      AUC leptin (EDD-700 d) (r = 0.62, p = 0.002). CHL SDS at EDD correlated with AUC
      IGFBP-3 and leptin (birth-EDD), but IGFBP-3 was the best predictor (r = 0.55, p <
      0.0001). CHL at EDD + 700 d correlated with AUC IGF-I and IGFBP-3 (EDD-700 d),
      but IGFBP-3 was the best predictor (r = 0.47, p = 0.01). Wt and CHL at birth were
      associated with IGFBP-3 levels in these infants. Wt at EDD and EDD + 700 d was
      predicted by concurrent leptin output while linear growth at EDD and EDD + 700 d
      was predicted by IGFBP-3 output.

PMID- 17211150
TI  - Major determinants of height development in Turner syndrome (TS) patients treated
      with GH: analysis of 987 patients from KIGS.
AB  - Little is known about factors determining height outcome during GH treatment in
      Turner syndrome (TS). We investigated 987 TS children within the Kabi
      International Growth Study (KIGS) who had reached near adult height (NAH) after
      >4 y GH treatment (including >1 y before puberty). Through multiple regression
      analysis we developed a model for NAH and total gain. Our results were as follows
      (median): 1) At start, age 9.7 yrs, height (HT) 118.0 cm (0.0 TS SDS), projected
      adult height 146.1 cm, GH dose 0.27 mg/kg wk; 2) NAH HT 151.0 cm (1.5 TS SDS); 3)
      Prepubertal gain 21.2 cm (1.6 TS SDS); 4) Pubertal gain 9.4 cm (0.0 TS SDS). NAH
      correlated (r = 0.67) with (ranked) HT at GH start (+), 1 year responsiveness to
      GH (+), MPH (+), age at puberty onset (+), age at GH start (-), and dose (+). The
      same factors explained (R = 0.90) the total HT gain. However, HT at GH start
      correlated negatively. Karyotype had no influence on outcome. Evidently, height
      at GH start (the taller, the better), age at GH start (the younger, the better),
      the responsiveness to GH (the higher, the better) and age at puberty (the later,
      the better) determine NAH.

PMID- 17211151
TI  - Early life factors predict abnormal growth and bone accretion at prepuberty in
      former premature infants with/without neonatal dexamethasone exposure.
AB  - Growth, bone, and body composition were studied at prepuberty in former very low
      birth weight (VLBW) infants who received dexamethasone (DEX) for bronchopulmonary
      dysplasia (BPD) compared with VLBW infants without DEX and term-born infants
      (TERM) to identify early life risk factors for later low bone mass. Children (56
      girls/63 boys, 5-10 y) previously studied in neonatal life were recruited into
      three groups: VLBW + DEX, VLBW - DEX, and TERM children. Anthropometry and whole
      body bone, fat, and lean mass were measured. At prepuberty, the average height
      and weight for VLBW + DEX group were significantly lower than that for VLBW - DEX
      and TERM. Both VLBW groups had lower bone mass even adjusted for height and lean
      mass than TERM children and lower lean mass both total and adjusted for height. Z
      scores for whole body bone mineral content below -1.5 occurred in 27.9% of VLBW +
      DEX children. The key factors for low bone mass were earlier gestational age and
      having BPD with DEX in neonatal life. In former VLBW infants, growth and bone
      mass attainment before puberty can be predicted from early life variables. VLBW +
      DEX children may be protected from overweight, but are at risk for short stature
      and low bone mass.

PMID- 17211152
TI  - NPHS1 and NPHS2 gene mutations in Chinese children with sporadic nephrotic
      syndrome.
AB  - Recent discoveries indicate that the molecules in glomerular podocytes and slit
      diaphragms may play an important role in the development of proteinuria and
      nephrotic syndrome. Mutational analyses of NPHS1 and NPHS2 were performed to
      verify this hypothesis in sporadic nephrotic syndrome (NS) patients. Clinical
      characteristics and DNA samples were collected from 38 Chinese children with
      sporadic steroid-sensitive NS, 22 with steroid-resistant NS and 30 controls.
      Direct sequencing was performed after PCR amplification of all 29 and 8 exons of
      the NPHS1 and NPHS2 genes, respectively. In NPHS1, 4 patients had heterozygous
      missense mutations leading to amino acid substitutions (R800C, Q453R).
      Furthermore, 3 known single nucleotide polymorphism (SNP) were found (T741T,
      V763V, S1105S). In NPHS2, 3 patients had novel heterozygous allelic variants
      leading to amino acid substitutions (S206I, E188D), while 1 patient was found to
      carry a novel nonsense mutation leading to a truncated protein product
      (Glu237STOP). Two known polymorphisms were also found (A318A, L346L). The results
      demonstrate that NPHS1 and NPHS2 mutations are also present in Chinese sporadic
      NS patients, suggesting that genetic changes of nephrin and podocin may play
      pathogenetic roles in some patients with sporadic steroid resistant NS.

PMID- 17211153
TI  - The functional state of neutrophils correlates with the severity of renal
      dysfunction in children with hemolytic uremic syndrome.
AB  - Hemolytic Uremic Syndrome (HUS) is the main cause of acute renal failure in
      children. The high percentage of patients who develop long-term sequelae
      constitutes an important medical concern. The identification of parameters that
      correlate with the degree of renal failure may be useful to plan the best
      treatment soon after hospitalization. Here, we investigated the functional state
      of neutrophils (PMN) from HUS patients on admission, before dialysis and/or
      transfusion, in relation to the severity of renal impairment reached during the
      acute period (AP). We found that all PMN activation parameters measured in severe
      cases of HUS (HUS AP3) were statistically lower comparing to children with mild
      cases of HUS (HUS AP1). As HUS PMN phenotype and dysfunction is compatible with
      that of cells undergoing cell death, we also studied spontaneous apoptosis. Not
      only were HUS PMN not apoptotic, but HUS AP3 PMN showed an increased survival.
      Almost all phenotypic and functional parameters measured on PMN correlated with
      severity. Our results revealed a marked deactivation of PMN in severe cases of
      HUS, and suggest that studying the functional state of PMN could be of prognostic
      value.

PMID- 17211154
TI  - Renal effects of beta2-adrenoceptor agonist and the clinical analysis in
      children.
AB  - The objectives of the present study were to define the contribution of beta2
      adrenoceptors (beta2-ARs) agonists to renal physiology and to investigate whether
      over-expression of renal beta2-ARs might be implicated in the pathogenesis of
      renal dysfunction in children as an adverse effect of beta2-AR activation. The
      renal functional responses to the systemic injection of the beta2-AR agonist
      terbutaline in Wistar rats over-expressing renal beta2-AR were compared with
      those of nontreated rats. Furthermore, we evaluated intrarenal beta2-AR
      expression in 34 children (age 2-15 y) and the changes in serum creatinine levels
      of 99 children (age 1-15 y) who received beta2-AR agonists. The animal study
      showed that the suppression of glomerular function by terbutaline was associated
      with a reduction in systemic blood pressure and over-expression of renal beta2
      ARs. Moreover, in rats over-expressing renal beta2-ARs, administration of
      terbutaline resulted in a high mortality rate after a lipopolysaccharide
      challenge. The clinical study showed that renal beta2-AR expression gradually
      increased with age and was up-regulated by steroid therapy. These findings
      indicate that the renal dysfunction caused by beta2-AR agonists can be explained,
      at least partly, by enhanced beta2-AR expression in the kidney. This may have
      important implications for the use of beta2-AR agonists in the treatment of sick
      children with, for example, steroid therapy or endotoxemia.

PMID- 17211155
TI  - Glutaryl-CoA dehydrogenase deficiency.

PMID- 17211158
TI  - Management of the patient with a large anterior mediastinal mass: recurring
      myths.
AB  - PURPOSE OF REVIEW: This editorial review summarizes the current anesthetic
      management of patients with anterior mediastinal masses. RECENT FINDINGS: With
      increased appreciation of the correct intraoperative management of these cases
      severe intraoperative respiratory or cardiovascular collapse is less likely to
      occur during general anesthesia. Maintenance of spontaneous ventilation is the
      anesthetic goal whenever possible. Major life-threatening complications now occur
      more frequently postoperatively. SUMMARY: General anesthesia is not safe in
      patients with severe positional symptoms from an anterior mediastinal mass. With
      modern imaging techniques, general anesthesia is rarely needed for diagnostic
      procedures in these patients. Preoperative flow-volume loops are not useful in
      the management of these patients and the concept of cardiopulmonary bypass on
      'standby' is not appropriate during induction of anesthesia.

PMID- 17211159
TI  - Pulmonary resection in the elderly.
AB  - PURPOSE OF REVIEW: With increasing longevity, altered demographics of the lung
      cancer population, and preoperative interventions to enhance the efficacy of
      surgical therapy, increasing numbers of elderly people will present for
      anesthesia and pulmonary resection. RECENT FINDINGS: The geriatric population
      often exhibits wide disparity between chronologic and physiologic senescence
      which is underscored by data indicating that outcome following lung resection for
      cancer is influenced more by tumor stage, preoperative functional status and
      comorbidities than age alone. Nonetheless, the normal process of cardiopulmonary
      aging can limit the physiological reserve necessary to compensate for
      perioperative stress even in otherwise healthy elderly patients. Data indicate a
      relatively favorable risk-benefit relationship for lung resection in the elderly
      given the poor prognosis for patients undergoing palliative care or chemotherapy
      or radiation alone. Emerging experience now suggests that minimally invasive
      surgical techniques for the treatment of lung cancer may parallel conventional
      thoracotomy in terms of oncologic efficacy while decreasing perioperative
      morbidity in the elderly. SUMMARY: The combination of an aging population, recent
      advances in neoadjuvant therapies, data supporting the oncologic efficacy of
      resection, and minimally invasive surgical techniques strongly suggests that more
      elderly patients will be candidates for surgical management of their lung cancer,
      thus presenting anesthesiologists with unique challenges.

PMID- 17211161
TI  - Anaesthesia for oesophagectomy.
AB  - PURPOSE OF REVIEW: To review the current anaesthetic management of patients
      undergoing transthoracic oesophagectomy. RECENT FINDINGS: Oesophageal
      adenocarcinoma is increasing rapidly in the West. The perioperative mortality for
      oesophagectomy remains high. A relationship has been established between volume
      and outcome for oesophageal surgery. There is little evidence from randomized
      clinical studies to guide the management of patients undergoing oesophagectomy.
      The profile of patients presenting for oesophagectomy is changing. There is
      emerging evidence that anaesthetic management influences outcome. At present
      there are no clear advantages for minimal access surgery. SUMMARY: Although
      nonsurgical treatments are being developed, at present surgery remains the
      mainstay of potentially curative treatment. Accurate risk stratification would
      greatly facilitate the assessment of strategies to reduce operative mortality.
      Anaesthetic research has the potential to further improve the safety of patients
      undergoing oesophageal surgery.

PMID- 17211160
TI  - Anesthesia for thoracic surgery in morbidly obese patients.
AB  - PURPOSE OF REVIEW: This review considers the anesthetic management of obese
      patients undergoing thoracic surgery. Extremely or morbidly obese patients differ
      from patients of normal weight in several ways. Obese patients have altered
      anatomy and physiology, and usually have associated comorbid medical conditions
      that may complicate their operative course and increase their risks for
      postoperative complications. RECENT FINDINGS: During anesthetic induction and
      laryngoscopy for tracheal intubation the morbidly obese patient should be in the
      reverse Trendelenburg position with the head and neck elevated above the table.
      Placement of a double-lumen tube should be no more difficult in an obese patient
      than in a normal-weight patient. There are no clear advantages for any of the
      commonly available inhalational anesthetic agents and each can be used for
      general anesthesia. SUMMARY: With proper attention to their special needs, the
      morbidly obese patient can safely undergo thoracic surgery and one-lung
      ventilation.

PMID- 17211162
TI  - Lung transplantation.
AB  - PURPOSE OF REVIEW: To describe recent advances in lung transplantation relevant
      to anesthesiologists. RECENT FINDINGS: There is recent literature describing
      medical, surgical, anesthetic and critical care of lung transplant recipients.
      SUMMARY: There have been substantial changes in preoperative selection and
      preparation of lung transplant recipients; these include donation after cardiac
      death, and improved lung-preservation solutions. Newer immunosuppression regimens
      have been successfully evaluated in clinical trials. Particular advances in
      anesthesia include endorsement of fluid restriction in thoracic surgery, greater
      use of transesophageal echocardiography, and postoperative extracorporeal
      membrane oxygenation.

PMID- 17211163
TI  - Which device should be considered the best for lung isolation: double-lumen
      endotracheal tube versus bronchial blockers.
AB  - PURPOSE OF REVIEW: This review is a clinical comparison between double-lumen
      endotracheal tubes and bronchial blockers to determine which device is considered
      the best for lung isolation. RECENT FINDINGS: Double-lumen endotracheal tubes and
      bronchial blockers have been found to be clinically equivalent in terms of
      performance in providing lung collapse for patients with normal airways. In the
      last five years, however, numerous reports have indicated a preference for the
      use of bronchial blockers in patients with airway abnormalities. For nonthoracic
      anesthesiologists who have limited experience in thoracic anesthesia cases, none
      of the devices (double-lumen tubes or bronchial blockers) have been shown to
      provide any advantage while in use due to a high incidence of unrecognized
      malpositions. Overall, each device provides advantages depending upon the case,
      such as absolute lung separation with a double-lumen endotracheal tube or the use
      of a bronchial blocker in a difficult airway for a patient requiring lung
      isolation. SUMMARY: Double-lumen endotracheal tubes and bronchial blockers should
      be part of the armamentarium of every anesthesiologist involved in lung isolation
      techniques and every device should be tailored to specific case needs.

PMID- 17211164
TI  - Exploring the perioptome: the role of genomics in thoracic surgery and
      anaesthesia.
AB  - PURPOSE OF REVIEW: Genetic variation almost certainly affects every aspect of a
      patient's perioperative experience, yet almost nothing is known of the details
      involved. This review introduces the concept of static and dynamic genetic
      variation as a determinant of outcome after thoracic surgery and discusses some
      of the methodological issues involved in its study. Using a systems biology
      approach, it explores the ways in which data from many sources may be integrated
      into a common model of disease risk and outcome prediction. RECENT FINDINGS: The
      incidence of mortality and morbidity after lung resection is unacceptably high,
      and has changed little in the last 20 years. New approaches to this problem are
      required if we are to improve outcomes after thoracic surgery. SUMMARY: Patients
      seem to be predisposed to respond to a surgical stimulus in heterogeneous
      fashion, and this may be partly explained by variability in the genetic
      background with which they present for surgery. Although recent pilot data
      suggest that this is indeed the case, much more work remains to be done before
      this can be confirmed.

PMID- 17211165
TI  - Atelectasis in the perioperative patient.
AB  - PURPOSE OF REVIEW: To report the impact of atelectasis on perioperative outcomes.
      Atelectasis occurs in the dependent parts of the lungs of most patients who are
      anesthetized. Development of atelectasis is associated with decreased lung
      compliance, impairment of oxygenation, increased pulmonary vascular resistance
      and development of lung injury. Here, we examine the etiology, contributing
      factors, consequences, diagnosis and treatment of atelectasis. RECENT FINDINGS:
      Atelectasis describes the state of absent air in alveoli attributable to
      collapse, but recent findings suggest that alveoli are filled with foam and
      fluid. It is now known that atelectasis plays an important role beyond abnormal
      gas exchange and that prevention or reversal of atelectasis in some populations
      of postoperative patients may improve outcome. SUMMARY: Atelectasis in the
      presence of preexisting lung disease or limited cardiopulmonary reserve may have
      significant consequences. Increasing understanding of the underlying nature of
      atelectasis and its contribution to acute lung injury will improve our approach
      to the prevention and management of atelectasis.

PMID- 17211166
TI  - Postthoracotomy atrial fibrillation.
AB  - PURPOSE OF REVIEW: Rapid atrial arrhythmias affect the elderly who undergo
      cardiac or noncardiac operations annually and have been associated with prolonged
      hospital stays. This article focuses on new issues leading to the improved
      understanding of the pathophysiology and mechanisms of postoperative atrial
      arrhythmias. RECENT FINDINGS: New risk factors and a prediction rule for
      postthoracotomy atrial fibrillation are discussed. Settings in which amiodarone
      prophylaxis against atrial fibrillation after cardiac surgery is appropriate are
      contrasted with evidence for postthoracotomy atrial fibrillation. Once atrial
      fibrillation develops, rate versus rhythm control strategies are reviewed. The
      most recent recommendations of the American Heart Association Task Force on the
      management of patients with atrial fibrillation are highlighted. SUMMARY: Recent
      approaches directed at prophylaxis and acute therapy of atrial arrhythmias are
      discussed as are recommendations to prevent thromboembolic events.

PMID- 17211167
TI  - Iatrogenic pulmonary artery rupture.
AB  - PURPOSE OF REVIEW: Pulmonary artery rupture is probably the most devastating
      complication associated with the use of the pulmonary artery catheter. This rare
      but disastrous situation requires a clear intervention plan. RECENT FINDINGS: The
      initial presentation of pulmonary artery ruptures may be as obvious as a massive
      pulmonary hemorrhage or as subtle as a cough associated with minimal hemoptysis,
      or it may even be totally asymptomatic. A patient presenting any clinical
      manifestation of pulmonary artery rupture may develop a pulmonary artery false
      aneurysm, which is the accumulation of blood in an aneurismal sac compressed by
      lung parenchyma. This condition requires intervention because delayed hemorrhage
      may occur and recurrence can be massive and fatal. Following an initial episode
      of suspected pulmonary artery rupture, the patient should undergo immediate
      radiological investigation. If a diagnosis of pulmonary artery false aneurysm is
      confirmed, selective angiographic embolization helps reduce morbidity and
      mortality. SUMMARY: The incidence of pulmonary artery ruptures is probably
      underestimated because many hemoptysis episodes or radiological infiltrations
      associated with pulmonary artery catheter use are not investigated. Also, the
      natural evolution of the pulmonary artery false aneurysm is unknown. The
      incidence of spontaneous healing, bleeding recurrence or asymptomatic persistence
      is unknown following formation of a pulmonary artery false aneurysm.

PMID- 17211168
TI  - Non-antiarrhythmic agents for prevention of postoperative atrial fibrillation:
      role of statins.
AB  - PURPOSE OF REVIEW: Atrial fibrillation is the most common arrhythmia following
      cardiac surgery, having both serious medical and socioeconomic consequences.
      Although there are established antiarrhythmic agents for preventing and treating
      postoperative atrial fibrillation, these therapies are neither 100% reliable, nor
      without risks and limitations. Thus, there remains a strong need for non
      antiarrhythmic, adjunctive therapies for the prevention of postoperative atrial
      fibrillation. RECENT FINDINGS: Long-term statin administration in ambulatory
      patients is associated with a reduced risk of adverse cardiovascular events,
      including death, myocardial infarction, stroke, renal dysfunction and atrial
      fibrillation. Recent evidence suggests, however, that statins may also reduce the
      risk of acute adverse outcomes following invasive procedures, including
      postoperative atrial fibrillation. Although the exact mechanisms by which statins
      may reduce postoperative atrial fibrillation are unclear, accumulating evidence
      suggests that statins exert multiple effects independent of their effect on LDL
      cholesterol. For example, in patients with acute coronary syndromes, statin
      therapy has been shown to modulate remodeling of the cardiac extracellular matrix
      and to reduce markers of inflammation, including C-reactive protein, serum
      amyloid A, tumor necrosis factor-alpha, and IL-6. SUMMARY: Perioperative statin
      therapy may represent an important non-antiarrhythmic, adjunctive therapeutic
      strategy for the prevention of postoperative atrial fibrillation.

PMID- 17211170
TI  - Heart and kidneys: sharing more than just blood.
AB  - PURPOSE OF REVIEW: To describe the relationship of renal disease and metabolic
      syndrome with cardiovascular disease and explore the role of toxic solutes
      retained due to renal impairment as mediators of cardiovascular risk. RECENT
      FINDINGS: Metabolic syndrome and chronic kidney disease are related. Chronic
      kidney disease is partly caused by, but also mediates, some of the adverse
      effects of metabolic syndrome. Uremic toxins with potent effects have been
      identified. Examples include the nitric oxide synthase inhibitor asymmetric
      dimethyl arginine - this substance accumulates as renal function declines and has
      a strong relationship with cardiovascular events and mortality in a variety of
      populations. The effect of asymmetric dimethyl arginine in causing arterial
      stiffness, a phenomenon which has been linked with risk of vascular disease,
      offers a mechanistic explanation for the importance of this substance. SUMMARY: A
      pathophysiology that links renal impairment with cardiovascular risk has long
      been suspected and is being elucidated through the effects of uremic toxins.

PMID- 17211169
TI  - Anemia and morbidity and mortality in coronary bypass surgery.
AB  - PURPOSE OF REVIEW: Anemia is associated with increased morbidity and mortality,
      in community-dwelling persons, in critically ill patients and perioperatively.
      The exact reasons and extent of the risks induced by anemia are not known,
      however, nor the optimal therapeutic approach. Based on the assumption that
      transfusion invariably counteracts the risks associated with perioperative
      anemia, most studies do not exclude the confounding effects of transfusion, and
      anemia is inconsistently defined. Cardiovascular disease was identified as a
      major additional risk for anemic patients, but the combined effects of decreasing
      hemoglobin and comorbidities in patients with coronary stenoses have not been
      determined exactly. This review integrates recent data to present a more
      differentiated understanding of mechanisms and risks of anemia in coronary artery
      bypass grafting surgery. RECENT FINDINGS: Patients with many comorbidities are
      more susceptible to the effects of anemia. Some outcomes may primarily be caused
      by concomitant risk factors associated with anemia rather than by low hemoglobin
      per se. The precise interactions of anemia and comorbidities to produce worse
      outcomes are still unclear, as is the optimal therapeutic approach. SUMMARY: The
      review highlights recent developments on anemia in heart surgery, and advocates
      new studies to institute individually adapted therapies.

PMID- 17211171
TI  - Percutaneous valve interventions.
AB  - PURPOSE OF REVIEW: Open heart surgery has long been considered the gold standard
      for treatment of patients with valvular heart disease. Although results are
      excellent, this technique requires the use of cardiopulmonary bypass and is
      associated with protracted recovery and attendant risks of open surgery. The
      field of percutaneous valve interventions has emerged as a closed-chest
      alternative for all patients, but particularly those who otherwise would be
      considered too high risk for open surgery. RECENT FINDINGS: Several devices are
      currently being evaluated in the clinical realm for each heart valve,
      particularly for the aortic and mitral positions. Early results are promising,
      but longer follow-up is necessary to determine durability of the procedures.
      SUMMARY: Although only in its infancy, percutaneous valve therapies offer heart
      valve interventions without the use of cardiopulmonary bypass. This creates many
      new possibilities for patients, especially those who are deemed either high risk
      or inoperable by the usual surgical standards. Newer device iterations and longer
      term follow-up will be necessary as the field moves forward.

PMID- 17211173
TI  - Bibliography. Current world literature. Thoracic anaesthesia.

PMID- 17211172
TI  - Current trends in coronary artery disease in women.
AB  - PURPOSE OF REVIEW: There are some striking sex differences regarding
      presentation, symptoms and sign, diagnosis, and treatment of coronary artery
      disease. Historically, healthcare delivery to women has been plagued with
      treatment bias favoring men. This review will present relevant cardiovascular
      physiologic sex differences, current treatment options for coronary artery
      disease both surgical and medical, and clinical outcomes of such treatments.
      RECENT FINDINGS: In the past, pharmacologic and interventional studies generally
      excluded women from their subjects. As a result, women have been traditionally
      treated based on the findings in their male counterparts. Recent studies
      examining sex differences in the treatment of coronary artery disease have given
      new insight into the hormonal and behavioral influences associated with coronary
      artery disease. Finally, these studies have drawn attention to possibly
      inadvertent discrepancies in the way men and women are treated for coronary
      artery disease. SUMMARY: Despite significant advances in medical and surgical
      approaches to treat coronary artery disease, it remains and will continue to be
      the most important healthcare challenge of the 21st century. Whereas efforts are
      underway to encourage inclusion of more women in therapeutic trials, the
      educational process, particularly in medical school, needs to broadly address sex
      specific pathophysiology and treatment, rather than relying on sub-subspecialty
      training for optimizing healthcare delivery in women.

PMID- 17211175
TI  - Anterior endoscopic skull-base surgery getting started: an otolaryngologist's
      perspective.
AB  - PURPOSE OF REVIEW: Anterior endoscopic skull-base surgery is a relatively new
      field requiring new levels of cooperation between otolaryngology and
      neurosurgery. The formation of these teams is discussed along with their
      challenges. RECENT FINDINGS: A significant amount of literature has been produced
      in the last few years, chronicling new and innovative techniques for anterior
      endoscopic skull-base surgery. These techniques are requiring close coordination
      between otolaryngologist and neurosurgeon in a multidisciplinary approach.
      However, there are obstacles to overcome in forming these teams. SUMMARY:
      Anterior endoscopic skull-base surgery is a technically challenging skill set
      which requires multiple factors to perform successfully. Factors to overcome
      require surgical training, appropriate patient base, specialized equipment and
      institutional inertia. These obstacles may be overcome in the majority of
      centers.

PMID- 17211176
TI  - Adult chronic rhinosinusitis: surgical outcomes and the role of endoscopic sinus
      surgery.
AB  - PURPOSE OF REVIEW: To review the recent literature as to the role of and data
      supporting endoscopic sinus surgery for the treatment of adult chronic
      rhinosinusitis. RECENT FINDINGS: Many studies have been published evaluating
      patient responses to endoscopic sinus surgery. These responses have included
      subjective measures such as patient-reported symptoms, and subjective symptoms
      measured objectively, as seen with quality-of-life instruments. Others have used
      objective measures such as endoscopy scores, medication use and financial impact
      to measure responses to surgery. These studies have varying follow-up, with
      patients followed for up to several years postsurgery. The results are very
      consistent, with most studies reporting improvement in both subjective and
      objective findings postoperatively. SUMMARY: The data in the literature clearly
      support the use of functional endoscopic sinus surgery in cases of chronic
      rhinosinusitis refractory to medical therapy. Surgery has been shown to improve
      patient symptoms, quality of life and intranasal endoscopic exam.

PMID- 17211177
TI  - An immunological approach to chronic and recurrent sinusitis.
AB  - PURPOSE OF REVIEW: Sinusitis is an illness that is often successfully treated by
      primary care physicians. Recurrent or chronic rhinosinusitis, however, can be
      frustrating for patients as well as primary care and subspecialty providers. The
      present review details the approach to recurrent or chronic sinusitis. We give a
      broad overview of the workup of chronic rhinosinusitis, focusing on immune
      deficiency, an often overlooked but clinically important aspect of the sinusitis
      workup. RECENT FINDINGS: Immune deficiency is prevalent in patients with
      recurrent or chronic sinus disease. An immunologic workup, as well as a workup
      for other chronic treatable diseases, should be undertaken before sinus surgery
      or in patients who have been unresponsive to surgery. This approach can enhance
      visualization during surgery, minimize postoperative complications, improve
      surgical outcomes, and possibly obviate the need for surgery altogether. SUMMARY:
      Elucidating the cause of recurrent or refractory sinus disease can be
      challenging. Allergic disease should be evaluated and treated early in the
      process. An immunologic evaluation should be performed and uncommon causes of
      sinus inflammation should be addressed later in the course to reduce inflammation
      either to avoid surgery or improve surgical outcomes.

PMID- 17211178
TI  - Allergic fungal rhinosinusitis: diagnosis and management.
AB  - PURPOSE OF REVIEW: The proper diagnosis and treatment of allergic fungal
      rhinosinusitis remain controversial. We discuss recent additions to the
      literature regarding diagnosis and treatment of this condition. RECENT FINDINGS:
      There is considerable overlap in the clinical features of allergic fungal
      rhinosinusitis and other forms of eosinophilic mucin chronic rhinosinusitis. Type
      1 hypersensitivity and characteristic computed tomographic findings may have
      predictive value for a final diagnosis of allergic fungal rhinosinusitis,
      patients with which are more likely to have bony erosion than patients with other
      forms of chronic rhinosinusitis. The decreases in orbital volume associated with
      expansive allergic fungal rhinosinusitis disease may spontaneously improve after
      successful treatment. Most patients have detectable fungal-specific IgE in their
      so-called allergic mucin. Elevated levels of fungal-specific IgG3 are a
      consistent finding in patients with allergic fungal rhinosinusitis and
      eosinophilic mucin chronic rhinosinusitis. Antifungal treatment is still
      considered a treatment option, but further study is needed. SUMMARY: Type 1
      hypersensitivity to fungal antigens helps to distinguish allergic fungal
      rhinosinusitis from other forms of eosinophilic mucin chronic rhinosinusitis.
      Bony erosion and orbital expansion giving rise to proptosis are prominent
      features of allergic fungal rhinosinusitis. Advances in medical treatment will
      require prospective and controlled trials.

PMID- 17211179
TI  - Intraoperative surgical navigation for endoscopic sinus surgery: rationale and
      indications.
AB  - PURPOSE OF REVIEW: The present review discusses the rationale and indications for
      image-guided surgery through a critical discussion of registration concepts as
      well as clinical reports. RECENT FINDINGS: The surgical navigation accuracy
      achieved by commercially available image-guided surgery systems is best reported
      as target registration error. Clinically achievable target registration error is
      probably in the 1.5-2.0 mm range. Dry lab studies of registration serve to
      highlight the principles of registration, the process through which image-guided
      surgery systems calculate the one-to-one mapping relationship between the
      preoperative imaging data and the intraoperative surgical volume. Reports on
      image-guided surgery have highlighted its usefulness in primary and revision
      endoscopic sinus surgery, osteoplastic frontal sinusotomy, transsphenoidal
      hypophysectomy, endoscopic cerebrospinal fluid leak repair and endoscopic
      pterygomaxillary fossa biopsy. Both three-dimensional computed tomography
      angiography and computed tomography-magnetic resonance fusion images have been
      incorporated into IGS for advanced minimally invasive endoscopic skull base
      procedures. The American Academy of Otolaryngology-Head and Neck Surgery policy
      statement accurately summarizes the current consensus for image-guided surgery
      applications. SUMMARY: Image-guided surgery has emerged as an important
      technology, which both general otolaryngologists and subspecialty rhinologists
      can employ for a wide variety of procedures.

PMID- 17211180
TI  - Evaluation of spontaneous nasal cerebrospinal fluid leaks.
AB  - PURPOSE OF REVIEW: Spontaneous nasal cerebrospinal fluid (CSF) leaks represent a
      distinct clinical entity that presents important diagnostic and therapeutic
      challenges. Recognition of the proper demographic group and presenting symptoms,
      as well as the radiologic features of this disease process, are integral to
      making the appropriate diagnosis. In addition, this patient group requires
      special perioperative and intraoperative considerations for suitable management.
      RECENT FINDINGS: Current literature echoes previously published success rates for
      endoscopic repair of CSF leaks at or above 90%. Success rates for closure of
      spontaneous CSF leaks, however, continue to be the lowest in comparison with
      other CSF leak etiologies. The increased failure rate for spontaneous CSF leak
      repair is likely due to the increased intracranial pressure present in this
      patient group. Patients with spontaneous CSF leaks are increasingly being
      recognized as belonging to a group inclusive of patients with benign intracranial
      hypertension and empty sella syndrome. SUMMARY: In this review, we highlight the
      demographic characteristics, clinical presentation and radiologic findings that
      distinguish spontaneous nasal CSF leak patients from those with other CSF leak
      etiologies. We also discuss perioperative measures advocated for patients with
      spontaneous nasal CSF leaks that may aid in the success of their surgical repair.

PMID- 17211181
TI  - Endoscopic CSF leak repair.
AB  - PURPOSE OF REVIEW: The purpose of this review is to discuss endoscopic management
      of cerebrospinal fluid leaks and to highlight recent advances in both outcomes
      and technique. RECENT FINDINGS: Endoscopic techniques targeting the repair of
      skull-base defects have evolved as instrumentation for intranasal use has
      developed. The principles of endoscopic repair mirror those of open repair, with
      emphasis placed on site identification, site preparation, accurate graft
      placement and postoperative management. Several patient factors will affect the
      surgical and medical care of patients with cerebrospinal fluid rhinorrhea,
      including location, cause and overall medical condition. Numerous techniques have
      been described and large series attest to high success rates. The use of
      radiographic image-guidance systems promises to advance localization of the leak
      site. Endoscopic repair of cerebrospinal fluid leaks remains an accurate and
      complete method for the repair of cerebrospinal fluid leaks with decreased
      operative morbidity. SUMMARY: Endoscopic repair of anterior skull-base defects
      has a high success rate and markedly decreased morbidity as compared with
      traditional intracranial approaches. The endoscopic approach should be considered
      the technique of choice for repair of most cerebrospinal fluid fistulae and skull
      base defects.

PMID- 17211182
TI  - Mitomycin C and endoscopic sinus surgery: where are we?
AB  - PURPOSE OF REVIEW: Mitomycin C has been used successfully in various
      ophthalmologic and, more recently, otolaryngologic procedures. Its modulation of
      fibroblast activity allows for decreased scarring and fibrosis. Several recent
      trials have examined the efficacy of mitomycin C in reducing synechia and
      stenosis following endoscopic sinus surgery. RECENT FINDINGS: Basic science
      studies using fibroblast cell lines have demonstrated a dose-dependent
      suppression of activity with the use of mitomycin C. This is further supported by
      animal studies that have shown lower rates of maxillary ostial restenosis
      following application of mitomycin C. No human trial, however, has demonstrated a
      statistically significant impact of mitomycin C on the incidence of postoperative
      synechia or stenosis following sinus surgery. The limitations of the literature
      are discussed. SUMMARY: The antiproliferative properties of mitomycin C may
      theoretically decrease the incidence of synechia and stenosis following
      endoscopic sinus surgery. Although this is supported by basic science studies and
      its successful use in other fields, the clinical evidence to date has not shown
      the application of mitomycin C to be effective in preventing stenosis after
      endoscopic sinus surgery. Future prospective studies are required before
      definitive conclusions can be made.

PMID- 17211184
TI  - Bibliography. Current world literature. Nose and paranasal sinuses.

PMID- 17211183
TI  - Biomaterials for sinus implantation.
AB  - PURPOSE OF REVIEW: Biomaterials are frequently used in the paranasal sinuses to
      control bleeding, promote tissue regeneration, improve healing, or prevent
      scarring. Few, however, have been prospectively examined in a peer-reviewed
      format prior to commercialization. This paper examines recent advances in
      biomaterials used in surgical rhinology and especially highlights some
      'postmarketing' concerns. RECENT FINDINGS: Three biomaterials have received
      recent attention. The use of hydroxyapatite cement within the frontal sinus has
      been questioned due to recent data regarding late infection and exposure.
      Thrombin-gelatin paste has been shown to be effective in controlling bleeding
      following sinus surgery but there are conflicting data about its effect on
      increased scarring. Hyaluronan derivatives have also received attention, with
      scarring concerns again raised. Importantly, it appears that the chemical
      modifications of the starting material may have a significant impact on
      compatibility and function. SUMMARY: Surgeons must be aware of the potential
      risks and limitations of biomaterials used in rhinology. While recent and future
      advances in biomaterials will likely improve patients' outcomes in sinus
      diseases, it is apparent that currently available materials may only be a first
      step to that goal. More rigorous prospective evaluation of biomaterials should
      guide their use in the paranasal sinuses.

PMID- 17211186
TI  - So many meetings and things to learn and so little time.

PMID- 17211187
TI  - Proteomics and systems biology in exercise and sport sciences research.
AB  - A systems biology approach toward biological research seeks to model all
      concurrent processes in a cell, tissue, or organism by global measurements. In
      this review, we describe recent advances in mass spectrometry-based proteomics
      and their application toward interpreting the physiological adaptations of
      skeletal muscle with exercise and obesity.

PMID- 17211188
TI  - Recommendations to define exercise prescription for Duchenne muscular dystrophy.
AB  - Duchenne muscular dystrophy yields pervasive and progressive muscle weakness.
      This weakness may be attenuated by regular, low-intensity exercise. However,
      there is a critical lack of data to support appropriate exercise prescription.
      Because inappropriate activity may exacerbate the dystrophic process, a
      systematic analysis of muscle function to determine potential exercise load
      thresholds to avoid injury in dystrophic mice and dogs, and then in humans, is
      recommended.

PMID- 17211189
TI  - Modest exercise prevents the progressive disease associated with physical
      inactivity.
AB  - Activity levels continue to decline as technology continues to engineer movement
      out of our environment. We summarize the findings from Studies Targeting Risk
      Reduction Interventions through Defined Exercise (STRRIDE) emphasizing the high
      cost of even short-term continued inactivity in sedentary, overweight, or mildly
      obese individuals. There seems to be a critical minimal level of physical
      activity required to maintain metabolic health. A modest amount of exercise seems
      to prevent metabolic deterioration.

PMID- 17211190
TI  - Physical activity and dementia: The need for prevention trials.
AB  - Dementia is a common and debilitating disease that will increase dramatically for
      the next 50 years unless a prevention or treatment is identified. This review
      summarizes the evidence that physical activity is associated with a reduced risk
      of dementia in older adults and recommends that prevention trials be performed to
      determine whether this association is causal.

PMID- 17211191
TI  - ACTN3: A genetic influence on muscle function and athletic performance.
AB  - A common variant of the ACTN3 gene, R577X, results in complete deficiency of the
      alpha-actinin-3 protein in the fast skeletal muscle fibers of more than a billion
      humans worldwide. We review the evidence that this genetic variant is strongly
      associated with elite athlete status and with normal variation in human muscle
      strength and sprinting speed.

PMID- 17211192
TI  - Stress and exercise: Getting the balance right for aging immunity.
AB  - Age-related immunological and endocrinological changes may have implications for
      resilience to stress in older adults. We hypothesize that the combination of
      adrenopause and immunosenescence may leave this population particularly
      vulnerable to the negative effects of stress on immunity. We propose that
      exercise may be an effective intervention to limit the impact of stress on
      immunity in chronically stressed older populations.

PMID- 17211193
TI  - American Burn Association Presidential Address 2006 on Nutrition: yesterday,
      today, and tomorrow.

PMID- 17211194
TI  - A novel antibacterial gene transfer treatment for multidrug-resistant
      Acinetobacter baumannii-induced burn sepsis.
AB  - Sepsis caused by multidrug-resistant bacterial infections in critically injured
      patients has become a major clinical problem. Recently, Acinetobacter baumannii
      (AB) wound infections, especially in our critically injured soldiers fighting in
      Iraq and Afghanistan, is posing a major clinical problem and an economic burden.
      ConjuGon, Inc., has developed a novel antibacterial therapeutic technology using
      bacterial conjugation. The donor cells are attenuated Escherichia coli carrying a
      conjugative plasmid. The expression of bactericidal genes cloned on the plasmid
      is tightly repressed in the donor cells but becomes de-repressed once mobilized
      into a pathogen and disrupts protein synthesis. Here, we tested the efficacy of
      this novel conjugation technology to control and eradicate a drug-resistant
      clinical isolate of AB wound infection both in vitro and in a murine burn sepsis
      model. C57Blk/6J mice were divided into burn (B) and burn sepsis (BS) groups. All
      animals received a 12% TBSA dorsal scald full-thickness burn. The BS group was
      inoculated with multidrug-resistant AB (1 x 10(5) colony-forming units [CFU]) at
      the burn wound site. BS animals were either untreated or treated with increasing
      concentrations (10(3) - 19(10) CFU) of attenuated donor E. coli encoding
      bactericidal proteins. The survival rate was monitored for 10 days. The ability
      of donor cells to significantly diminish AB levels in the burn wound 24 hours
      after injury was determined by quantitative cultures. Donor cells were highly
      effective in killing AB in vitro. In the burn sepsis model, 90% B group animals
      survived, and 40% to 50% BS animals survived with no treatment in 5 to 6 days.
      Treatment with donor cells at 10(10) to 10(6) provided significant survival
      advantage (P < .05). Quantitative cultures of burn wounds revealed that AB
      numbers increased from 3 x 10(4) CFU to 7.8 +/- 4.4 x 10(9) CFU in 24 hours in
      the untreated group. Single treatment with donor cells (10(10) CFU) significantly
      reduced AB in the burn wound to less than the levels seeded into the wound (1.23
      +/- 0.5 x 10(4) CFU; P < .05). Taken together, these results indicate that this
      novel technology is an efficient method to control drug-resistant AB burn wound
      infections and prevent their systemic spread.

PMID- 17211195
TI  - Repetitive ischemia-reperfusion injury: a plausible mechanism for documented
      clinical burn-depth progression after thermal injury.
AB  - Our previous studies confirmed the phenomenon of burn depth progression despite
      adequate Parkland formula resuscitation [Kim et al. J Burn Care Rehabil
      2001;22960:406-6]. Repetitive ischemia-reperfusion injury (I-R) is a plausible
      explanation and is suggested by the concomitant swings we have observed in serum
      base deficit (BD) during resuscitation from burn shock. We chose to explore
      whether laser Doppler imaging (LDI) evidence of burn depth progression mirrored
      cycles of I-R (episodic swings in continuously measured BD). Positive findings
      would support the hypothesis that repetitive episodes of I-R is a factor in burn
      depth progression despite apparently adequate resuscitation. A total of 14
      patients with severe life-threatening burns (median 51% TBSA) underwent
      continuous BD monitoring using a Paratrend 7 (Malvern PA) during 48 hours of
      resuscitation. Fluid needs were estimated using the Parkland formula, then were
      titrated to urine output. The slopes of BD changes were then analyzed. Worsening
      of BD greater than 0.2 mmol/l/min was noted, and a proportion derived relative to
      pooled data on 5-minute intervals. In four of the patients, LDI scans were
      performed on six representative areas sequentially every 4 hours. The analysis of
      median flux in these LDI images provided real-time determination of burn depth
      progression. Eight patients eventually died. Only four patients achieved a normal
      BD within 12 hours of monitoring despite exceeding the Parkland formula estimate
      and meeting urinary output parameters. Our analysis also showed cyclical peaks
      and valleys in the BD curve (P < .001), suggesting repetitive I-R insults. All
      increases in BD preceded changes that could be detected in vital signs or urine
      output. Finally, LDI confirmed that the burn depths continued to progress despite
      apparently adequate resuscitation, and also showed that there are similar peaks
      and valleys in the perfusion of the wounds (P < .0001), which mimic the changes
      in the BD curve. Responses to fluid resuscitation do not follow a linear pattern
      in the case of massive burns. These results in repetitive periods of tissue
      hypoperfusion evidenced by BD alterations and may contribute to progressive
      deepening of the burn wound.

PMID- 17211196
TI  - Burns as a result of assault: associated risk factors, injury characteristics,
      and outcomes.
AB  - The purpose of this study was to identify specific premorbid factors and injury
      characteristics associated with intentional burn injuries and to compare outcomes
      for individuals injured by assault and those with unintentional injuries.
      Participants sustaining major burns from May 1994 to August 2005 and consenting
      to a multisite, prospective, longitudinal outcome study were included. Etiology
      of the injury was classified as intentional (i.e., assault) or unintentional.
      Subjects <18 years old or with self-inflicted burns were excluded. Statistical
      analysis was performed with t-tests, chi2 tests, and analysis of variance. Eighty
      patients sustained intentional burn injuries and 1982 subjects sustained
      nonintentional burn injuries. Compared to patients with nonintentional burns,
      those with burns related to assault were more likely to be female, black, and
      unemployed and to have higher rates of premorbid substance use. Between the
      groups, there were no significant differences in preinjury living situation,
      education level, history of psychiatric treatment, or hospital length of stay.
      The intentional-burn group had larger burns and a greater in-hospital mortality
      rate, and these patients were less likely to be discharged to home. They also
      demonstrated significantly greater levels of psychological distress during the
      acute hospitalization but not at follow-up. Understanding the unique
      characteristics and needs of patients with intentional burn injuries is important
      because these individuals are less likely to have a steady income and more likely
      to rely on community social services. Affordable and accessible community-based
      health services are necessary in order to improve their outcomes.

PMID- 17211198
TI  - Suicide by self-immolation: comprehensive overview, experiences and suggestions.
AB  - Suicide by burning is a rare condition in the developed countries (0.06-1% of all
      suicides) but is more frequent in the developing countries (accounting for as
      many as 40.3% of all suicides). In different parts of Iran, between 1.39% and
      9.50% of patients that attempted suicide and 25.0% and 40.3% of patients who
      committed suicide were via deliberate self-burning. Self-burning (immolation)
      comprises between 0.37% and 40% of total burn center admissions around the world
      and, in Iran, it comprises between 4.1% and 36.6% of admissions in Iranian burn
      centers. Approximately 80% of hospitalized self-immolation patients die. The goal
      of this study was to identify the epidemiologic features, causes, and potential
      protective factors regarding suicide by burning in Kermanshah province, in the
      west of Iran, and to develop the effective intervention programs based on the
      Public Health Approach to Prevention. During the course of a year, from March 21,
      2004, to March 20, 2005 (based on the Iranian calendar), the author examined all
      the suicidal patients who were admitted to the emergency department of hospitals
      in Kermanshah University of Medical Science. Examination included a retrospective
      cross-section study, via demographic questionnaires and suicidal checklists.
      During the period of study, 1820 patients who attempted suicide and 90 patients
      who successfully committed suicide were admitted. A total of 41% (37 cases) of
      patients who committed suicide were via self-immolation. Of these, 81% of self
      immolation patients were female (P < .0005), and the female:male ratio was 4.3:1.
      A total of 86.5% of the patients were in the 11 to 30 years of age group. The
      mean age was 24.9 years (range, 14-50 years). Forty-nine percent of cases were
      single, 84% were illiterate or had a low level of education, 78.5% were
      housewives, and 14% were unemployed. Also, most of the patients (53%) were living
      in rural area, 97% did not have a previous history of suicide attempt, and 67.5%
      regretted their self-immolation act. The majority of the self-immolations (64.8%)
      occurred during daylight hours, and the most common self-immolation motivation
      factor was marital conflict (32.5%). Overall, this study demonstrates that self
      immolation should be considered as a mental health problem in our society, and it
      is necessary to implement programs and strategies to prevent it. The public
      health approach provides a framework for a National Prevention Strategy to
      address this serious national problem. Local data on victims and victim stories
      from self-immolation provided the stimulus for community action.

PMID- 17211199
TI  - Effects of differences in percent total body surface area estimation on fluid
      resuscitation of transferred burn patients.
AB  - We sought to analyze the effect that differences in estimation of burn size and
      burn resuscitation had on complications and death among our transferred burn
      patients, in comparison with outcomes for burn patients directly admitted to our
      rural Level 1 trauma center. A retrospective chart review was performed for all
      patients suffering thermal injuries who were treated at a rural Level I trauma
      center and regional burn center. Percent TBSA burn estimates at referring
      hospitals were compared to burn center estimates. The Parkland formula was used
      to calculate the difference between the theoretical and actual resuscitation
      volumes given prior to admission. Of 127 burn patients, 82 (65%) were transferred
      from outside hospitals. For small burns (<20% TBSA), the mean estimate difference
      between outside hospitals and the burn center was 4.3 +/- 6.9%. For large burns
      (> or =20% TBSA), the mean estimate difference was -4.9 +/- 9.1% (P < .0002). The
      mean difference in intravenous fluid administered prior to admission to the burn
      center and the Parkland formula guideline was an excess of 554 +/- 1099 ml for
      small burns and a deficit of -414 +/- 2081 ml for larger burns (P = .03,
      Wilcoxon's rank-sum test). Differences in burn estimation and deviation from the
      Parkland formula were not statistically significant for complication and death.
      In the rural, transferred burn patient, smaller burns tended to be overestimated
      and overresuscitated and larger burns tended to be underestimated and
      underresuscitated.

PMID- 17211201
TI  - Transfusion-related acute lung injury in patients with burns.
AB  - Transfusion-related acute lung injury (TRALI) has not been systematically
      described in patients with burn injury, and the characterization of TRALI in
      patients with pre-existing acute lung injury (ALI) or acute respiratory distress
      syndrome (ARDS) also is lacking. Our aim was to identify TRALI in burn patients
      and to attempt to characterize transfusion (TXN)-related pulmonary deterioration
      in burn patients with pre-existing ALI or ARDS. We undertook a retrospective
      review of mechanically ventilated and transfused burn patients at an adult
      regional burn center between January 1, 2003, and January 5, 2005. A blinded
      intensivist independently rated pre- and post-TXN chest radiographs (CXRs). There
      were 25 patients (age 51 +/- 19 years, %TBSA burns 30 +/- 19, full thickness %BSA
      17 +/- 19, with a 24% incidence of smoke inhalation) who received 124 TXNs. New
      ALI developed within 6 hours after four TXNs. In one TXN, there were no other
      precipitating causes (eg, infection, inhalation injury), suggesting possible
      TRALI (incidence 0.8%). Existing ALI or ARDS was present before 63 (51%) of the
      TXNs. Definite worsening of the CXR and deterioration in the PaO2/FiO2 ratio (18%
      +/- 4%) within 6 hours of TXN occurred after six transfusions. In two of the
      TXNs, there were no other precipitating causes, suggesting possible TXN-related
      pulmonary deterioration (incidence 3.2%). Vigilance must be maintained for TRALI
      in burn patients. For patients with existing ALI or ARDS, we suggest that
      worsening of the CXR and reduction in the PaO2/FiO2 ratio by 20% or more within 6
      hours of transfusion should be investigated for possible TRALI with appropriate
      donor investigations.

PMID- 17211200
TI  - An analysis of the long-distance transport of burn patients to a regional burn
      center.
AB  - The concentration of specialized burn care to relatively few centers within
      relatively large geographic regions requires an organized system of patient
      triage, referral, and transport. The purpose of this study was to identify
      systematic errors in either the initial evaluation or care of burn patients
      requiring transport more than 90 miles to a single regional burn center.
      Therefore, we undertook a descriptive analysis of patients transported more than
      90 miles to a single regional burn center from 2000 to 2003. The outcomes of
      interest were duration of transport, errors in burn size estimation, errors in
      fluid management, appropriateness of intubation, and complications during
      transport. During the years 2000 to 2003, there were 1877 admissions to the burn
      center; 949 (51%) were transferred from an outside facility. Of these 949, 424
      (45%) were transferred more than 90 miles from a referring facility to our burn
      center. The average transport time from injury to our burn center was 7.2 hours
      (range, 1.6-48). There were no patient deaths during transport, and the most
      common complications were loss of or inability to secure intravenous access and
      inability to secure an airway. Burn size estimates differed significantly (P <
      .001) between referring providers and burn center physicians. This study confirms
      that patients can be transported safely and efficiently over long distances to a
      regional burn center. Given the current geographic distribution of burn centers
      and concerns about declining numbers of burn surgeons, organized systems of
      patient triage and transport may become increasingly important.

PMID- 17211202
TI  - Effects of a restrictive blood transfusion policy on outcomes in children with
      burn injury.
AB  - A restrictive blood transfusion policy decreases blood utilization and improves
      outcomes in critically ill adults, but the impact of a restrictive blood
      transfusion policy in critically ill children is unclear. The study purpose was
      to compare the effects of a restrictive with a traditional blood transfusion
      policy in children with major burn injury. A retrospective review of all blood
      transfusions administered in a pediatric burn center during a 5-year period was
      conducted. Children in the traditional group (January 1, 2000, to June 30, 2002),
      were transfused at a hemoglobin level of less than 10 g/dl. Children in the
      restrictive group (January 1, 2003, to June 30, 2005, 6 months after the adoption
      of a restrictive protocol) were transfused at a hemoglobin level of less than 7
      g/dl. Patient groups were compared for demographics, ventilator requirements,
      blood transfusion number, transfusion costs, and outcomes. Of the 1140 patients
      studied, 266 (24%) received a total of 2577 units of blood. There was no
      difference in age, TBSA burn, sex, inhalation injury, or mortality between
      groups. Patients in the traditional group received more blood than the
      restrictive group (12.3 +/- 1.8 vs 7.2 +/- 1.2 units/patient, P < .001). The mean
      cost of blood per patient was $2781 for the traditional group and $1489 for the
      restrictive group. A restrictive transfusion policy in children with burn injury
      decreases the amount of blood transfused, does not adversely impact patient
      outcome, and results in significant cost savings to the institution.

PMID- 17211204
TI  - The clinical pulmonary infection score poorly predicts pneumonia in patients with
      burns.
AB  - The Clinical Pulmonary Infection Score (CPIS) has been reported to be a useful
      tool in the diagnosis of ventilator-associated pneumonia (VAP) in the critical
      care setting. However, the systemic inflammation associated with injury may limit
      the utility of CPIS in patients with burns. The purpose of this study was to
      determine the potential utility of CPIS in the management of burn patients. A
      retrospective review was performed on all burn patients who underwent
      quantitative culture to diagnose VAP from 2003 to 2005. CPIS was retrospectively
      calculated for each patient on the day of the procedure. The sensitivity,
      specificity, and predictive values of a CPIS greater than 6 for VAP diagnosis
      were calculated. In addition, CPIS scores of patients with and without pneumonia
      were compared using the Mann-Whitney U test. A total of 46 quantitative cultures
      were obtained in 28 patients during the study period. Average patient age was 45
      +/- 19 years, average TBSA was 33 +/- 18%, and the average APACHE II score on
      admission was 16 +/- 6. Sixty-eight percent of patients had inhalation injury.
      Twenty-six quantitative cultures were positive, and 20 were negative. Mean CPIS
      was 5.7 for patients with negative quantitative cultures and 5.5 for patients
      with positive cultures (P = .41). The sensitivity of CPIS scoring was 0.3, and
      its specificity was 0.8. CPIS had a positive predictive value of 0.7 and negative
      predictive value of 0.5. CPIS--a reported reliable indicator of VAP in critically
      ill patients--did not accurately predict the presence of pneumonia in burn
      patients. VAP diagnosis in burn patients should still rely on clinical suspicion
      verified by quantitative culture.

PMID- 17211203
TI  - Arterial and venous complications of heparin-induced thrombocytopenia in burn
      patients.
AB  - Heparin-induced thrombocytopenia (HIT) is an antibody-mediated complication of
      heparin treatment that can result in a number of devastating thrombotic
      complications. Given the common use of heparin for deep venous thrombosis
      prophylaxis in patients with burns, we reviewed the incidence and complications
      of HIT in our burn center. We performed a retrospective review of all patients
      treated with heparin at our burn center who underwent testing for HIT from 2001
      to 2005. Screening for HIT was performed by platelet factor 4 enzyme-linked
      immunoassay. Records were reviewed with particular attention to indications for
      HIT testing, duration of heparin therapy, type of heparin used (fractionated vs
      unfractionated), indication for heparin use (prophylactic vs therapeutic),
      treatment of HIT, and complications of HIT. During the 4-year study period, 625
      patients received heparin therapy at some point during their hospital course. Of
      these patients, 43 (6.9%) underwent testing for HIT and 10 of the 43 screened
      patients (23%) were positive; the incidence among all heparinized burn patients
      was 1.6%. Thrombotic complications of HIT included arterial thrombosis requiring
      limb amputation (two patients), deep venous thrombosis (three patients), and
      pulmonary embolism (two patients). One patient died, presumably secondary to a
      pulmonary embolism. All patients were anticoagulated after HIT diagnosis, and
      four patients developed bleeding complications. HIT is a potentially devastating
      complication of heparin administration. Whereas our overall incidence of HIT was
      low, HIT+ patients developed significant complications, including arterial and
      venous thrombosis, pulmonary embolus, limb loss, and death. Treatment for such
      HIT-related thromboses usually resulted in bleeding complications requiring
      transfusions. The routine use of heparin for deep venous thrombosis prophylaxis
      needs to be carefully considered in light of these potential complications.

PMID- 17211205
TI  - Inhalation injury, pulmonary perturbations, and fluid resuscitation.
AB  - Inhalation injury (INHI) associated with thermal injury has been shown to
      increase the rate of mortality. Several investigators have shown that patients
      with inhalation and burn injuries will require increased fluid volumes during
      acute resuscitation when compared with patients with burn injury alone. Other
      groups have examined the use of lung compliance and airway resistance as
      predictors of outcome in patients with INHI. We hypothesized that increased fluid
      requirements would more closely correlate with perturbations in pulmonary
      performance than with mere presence or absence of INHI or the degree of injury by
      bronchoscopic criteria. We performed a retrospective chart review during a period
      of 3 years. We identified 80 patients with suspected INHI that required
      intubation, mechanical ventilation, and fiber optic bronchoscopy in the first 24
      hours of their admission. Variables collected included age, sex, weight and %TBSA
      burned, as well as blood alcohol level, the presence of head and neck burns and
      escharotomies, and admission carbon monoxide levels. Patients were classified
      into five groups according to a grading system of INHI (0, 1, 2, 3, and 4),
      derived from findings at initial bronchoscopy and based on AIS criteria. The
      following pulmonary parameters were noted at regular intervals: mode of
      ventilation, tidal volume, peak inspiratory pressures, mean airway pressures, and
      compliance. The P:F ratio also was recorded at regular intervals. Total fluid
      volume infused was noted at 0-, 24-, and 48-hour intervals, and was calculated as
      ml/kg/%TBSA. Outcomes were measured by in-hospital survival, ventilator days,
      intensive care unit days, and total length of stay. Patients were well matched
      for %TBSA among the different bronchoscopic grades of INHI, and those with grades
      2, 3, and 4 injuries had a significantly worse survival than those with grades 0
      or 1 (P = .03). However, grades 2, 3, and 4 did not have increased acute fluid
      requirements when compared with grades 1 and 2 injuries. Initial pulmonary
      compliance likewise did not correlate with acute fluid requirements. However,
      those patients with a P:F ratio less than 350 at presentation had a statistically
      significant increase in ml/kg/%TBSA compared with those with P:F >350 (P = .03).
      They did not have more ventilator days or a statistically worse survival. Fiber
      optic bronchoscopy is useful in the diagnosis of INHI, and overall survival is
      worse in those patients with worse grades of injury by bronchoscopic criteria.
      However, the P:F ratio may be a more accurate predictor of increased fluid
      requirements during the acute resuscitation.

PMID- 17211206
TI  - The National Institute on Disability and Rehabilitation Research burn model
      system database: a tool for the multicenter study of the outcome of burn injury.
AB  - Advances in critical care and surgical management have significantly improved
      survival after burn injury over the past several decades. However, today,
      survival alone is an insufficient outcome. In 1994, the National Institute on
      Disability and Rehabilitation Research (NIDRR) created a burn model system
      program to evaluate the long-term sequelae of burn injuries. As part of this
      multicenter program, a comprehensive demographic and outcome database was
      developed to facilitate the study of a number of functional and psychosocial
      outcomes after burns. The purpose of this study is to review the database design
      and structure as well as the data obtained during the last 10 years. This is a
      descriptive study of the NIDRR database structure as well as the patient data
      obtained from the four participating burn centers from 1994 to 2004. Data
      obtained during hospitalization and at 6, 12, and 24 months after discharge were
      reviewed and descriptive statistics were calculated for select database fields.
      The database is divided into several subsections, including demographics, injury
      complications, patient disposition, and functional and psychological surveys. A
      total of 4600 patients have been entered into the NIDRR database. To date, 3449
      (75%) patients were alive at discharged and consented to follow-up data
      collection. The NIDRR database provides an expansive repository of patient,
      injury, and outcome data that can be used to analyze the impact of burn injury on
      physical and psychosocial function and for the design of interventions to enhance
      the quality of life of burn survivors.

PMID- 17211207
TI  - Preparing for burn disasters: evaluation of a continuing education training
      course for pre-hospital and hospital professionals in Kansas.
AB  - "Preparing for Burn Disasters: A Training Course for Pre-Hospital and Hospital
      Professionals in Kansas," a continuing education program designed to provide
      licensed health care practitioners a training opportunity for multiple burn
      victim incidents, emphasized the challenges that the community-wide
      multidisciplinary team faces when responding to burn disasters. A pre-post survey
      design was used to assess changes in participants' knowledge and self-rated
      ability, confidence, and competence to perform in a burn disaster before and
      after training. Participants (N = 383) were predominantly female (71.1%), 40
      years or older (57.7%), nurses (52.2%), were employed in a pre-hospital care
      setting (38%), and had worked in healthcare for 10 years or fewer (53.6%). The
      percentage of correct responses pre- vs post-test increased between 30% and 65%
      on two-thirds of the knowledge items. On the basis of paired-samples t-test
      analysis, statistically significant increases in participants' overall self
      ratings of ability and confidence in burn management were observed in every
      content area. Most participants (64%) felt competent or highly competent to
      manage multiple burn casualties after the training program, and most participants
      (58%) indicated that they intended to incorporate the newly acquired knowledge
      into their daily practice within 2 weeks. Evaluation results demonstrate that a
      successful program was designed and implemented. The curriculum and teaching
      methods achieved desired goals for improved knowledge, which appear to have been
      translated to enhanced abilities, confidence and competence in burn assessment
      and treatment modalities.

PMID- 17211208
TI  - Demographics of the homeless in an urban burn unit.
AB  - There are few articles about the homeless in burn literature. We sought to
      determine the demographic characteristics of the homeless citizens admitted to an
      urban burn center. This was a retrospective review from March 1999 to May 2004.
      Statistical analysis included chi2 and one-way analysis of variance. There were
      1615 burn admissions, and 73 (4.5%) of these patients were homeless. Although the
      %TBSA affected was similar for the homeless and domiciled patients, the mean (+/
      SD) age of the homeless was 44 +/- 10 years and their length of stay was 15 +/-
      15 days, compared with 31 +/- 22 years and 9 +/- 13 days, respectively, for the
      domiciled. Twenty-one (29%) of the 73 homeless were admitted for frostbite, vs 21
      (1.4%) of the 1542 domiciled patients (P= .000). Because of the frostbite, the
      majority (53%) arrived in the winter, compared with 15% in each of the other
      three seasons (P= .000). The homeless had a higher frequency of acute and chronic
      ethanol and cocaine use than the domiciled population (21% vs 6%). There was no
      significant difference between the homeless and the domiciled population in %TBSA
      affected, nutritional values, and assault frequency. More than half of the
      homeless patient admissions to the burn unit resulted from assault or frostbite.
      The homeless were mainly African-Americans and Caucasians, with a higher
      frequency of ethanol and cocaine use than in the domiciled burn population. Lack
      of discharge options for the homeless prolonged the average length of stay,
      leading to increased costs, often borne by the burn unit.

PMID- 17211209
TI  - A collaborative systems approach to rural burn care.
AB  - A collaborative systems approach was created between the regional verified burn
      center (BC) and the rural verified Level 1 trauma center (TC) to treat minor
      burns. This study assesses the feasibility of providing outpatient burn care at
      the TC. A retrospective review was performed from January 2000 to June 2005 of
      burn patients seen at the TC. Seven trauma/critical care surgeons and a dedicated
      burn nurse staffed the clinic twice a week. Burn surgeons from the BC provided
      consultation via email and telephone links and served as the regional resource.
      In the TC clinic, 314 injuries occurred in 311 patients. 196 patients were male
      with an average age of 34.5 +/- 1.1 years. The mean burn TBSA was 2.9 +/- 0.2%.
      Fourteen patients (4%) required skin grafts. Patients averaged 3.5 +/- 0.1 clinic
      visits over a mean follow-up period of 42.9 +/- 7.4 days from initial injury.
      There were 1252 scheduled appointments during the study period. Silver
      sulfadiazine or triple antibiotic ointment was applied in the majority of the
      cases. Thirty-one patients (9.9%) were documented to have complications, most of
      which were local wound infections. Long-term sequelae (scarring, chronic pain,
      and contractures) occurred in 13.4% of patients. Clinical success in outpatient
      burn care can be achieved at a non burn center with dedicated personnel. The
      successful collaboration between the BC and TC can unload some minor burn care
      from the burn center, while providing good clinical care to the local rural
      population.

PMID- 17211210
TI  - Two simple leg net devices designed to protect lower-extremity skin grafts and
      donor sites and prevent decubitus ulcer.
AB  - Burn therapists routinely are tasked to position the lower extremities of burn
      patients for pressure ulcer prevention, skin graft protection, donor site
      ventilation, and edema reduction. We developed two durable and low-maintenance
      devices that allow effective positioning of the lower extremities. The high
      profile and low-profile leg net devices were simple to fabricate and maintain.
      The frame was assembled using a three-quarter-inch diameter copper pipe and
      copper fittings (45 degrees, 90 degrees, and tees). A double layer of elasticized
      tubular netting was pulled over the frame and doubled back for leg support to
      complete the devices. The devices can be placed on any bed surface. The netting
      can be exchanged when soiled and the frame can be disinfected between patients
      using standard techniques. Both devices were used on approximately 250 patients
      for a total of 1200 treatment days. No incidence of pressure ulcer was observed,
      and graft take was not adversely affected. The devices have not required repairs
      or replacement. Medical providers reported they are easy to apply and effectively
      maintain proper positioning throughout application. Neither device interfered
      with the application of other positioning devices. Both devices were found to be
      an effective method of positioning lower extremities to prevent pressure ulcer,
      minimize graft loss and donor site morbidity, and reduce edema. The devices
      allowed for proper wound ventilation and protected grafted lower extremities on
      any bed surface. The devices are simple to fabricate and maintain. Both devices
      can be effectively used simultaneously with other positioning devices.

PMID- 17211211
TI  - Seven years' experience with Integra as a reconstructive tool.
AB  - The bilayered dermal substitute Integra (Integra Life Sciences Corp., Plainsboro,
      NJ) was developed and has been widely used as primary coverage for excised acute
      burns. Our take has been slightly different, finding it most useful in the
      management of complex soft-tissue loss and threatened extremities as the result
      of tendon, joint, or bone exposure. Often tasked to fill significant volume loss,
      we have become adept at stacked multiple-layer applications. Creative use of this
      material has resulted in unexpected successes with distal limb salvage; the
      technique takes its place beside adjacent tissue transfer, composite flaps, and
      vascular pedicle flaps in our burn reconstructive practice. A prospective
      registry (44 patients) has been kept during the past 7 years that catalogs wounds
      with complex soft-tissue loss treated with Integra grafts. Many of these patients
      were at risk of extremity loss because of exposed tendons, joints, or bone.
      Integra was applied after 1:1 meshing. With profound soft-tissue defects,
      multiple layers of Integra were serially applied 1 to 2 weeks apart for
      reconstitution of soft-tissue contours. Local Integra graft infections were
      managed by silicone unroofing followed by topical sulfamylon liquid dressings.
      Wounds addressed included fourth-degree burns, necrotizing fasciitis, pit-viper
      envenomations, and total abdominal wall avulsion in one patient after being run
      over by a bus. Patients generally were free of pain from their wounds during the
      maturation phase of the Integra neodermis. Restoration of tissue contour was
      significantly better when using multiple layers for deep defects. Second and
      third layers of Integra were successfully applied after an abbreviated first
      graft maturation period of 7 days. Epithelial autografts on multilayer Integra
      applications frequently "ghosted"; they would auto-digest to dispersed cells
      followed subsequently by the reappearance of a confluent epithelial layer. Final
      grafted skin morphology over palmar and plantar surfaces assumed the type and
      fingerprint pattern of the original tissues. Infections were readily visible.
      Early recognition kept them to easily treated circumscribed areas, which did not
      jeopardize the entire wound. Lengths of stay were long (range, 2-246 days) but
      not significantly greater than with traditional techniques. The specific
      reconstructive use of Integra permitted unexpected salvage of several threatened
      extremities by protecting exposed tendons, bones and joints. Long-term histologic
      examination revealed unexpected persistence of Integra collagen. Large volume
      loss wounds benefited from the ability to fill voids with multilayered
      applications.

PMID- 17211212
TI  - Expression of human beta defensin 4 in genetically modified keratinocytes
      enhances antimicrobial activity.
AB  - Defensins are cationic peptides of the innate host defense system with
      antimicrobial activity against many of the microorganisms commonly found in burn
      units. Beta defensins are variably expressed in the epithelia of skin and other
      organs. Human beta defensin 4 reportedly has antimicrobial activity against
      Pseudomonas aeruginosa and is not normally expressed in intact skin. Genetic
      modification was used to ectopically express human beta defensin 4 in cultured
      primary epidermal keratinocytes. Keratinocytes expressing human beta defensin 4
      showed significantly elevated antimicrobial activity against clinically-isolated
      P. aeruginosa compared with controls. These results suggest that genetic
      modification of keratinocytes can increase their resistance to microbial
      contamination. Bioengineered skin replacements containing human beta defensin 4
      modified keratinocytes may be useful for transplantation to contaminated burn
      wounds.

PMID- 17211214
TI  - Guidelines for the operation of burn centers.

PMID- 17211215
TI  - From the burn unit's perspective, it's lethal not being gainfully employed
      outside the home! A glimmer from the National Burn Repository.

PMID- 17211216
TI  - "Open for business!" a primer on the scholarly use of the National Burn
      Repository.

PMID- 17211218
TI  - Retrospective study of the association between hypertrophic burn scarring and
      bacterial colonization.
AB  - Although the association between hypertrophic burn scarring and infection is well
      described, an association with colonization has not been established. This
      retrospective study sought to determine whether a significant association between
      hypertrophic scarring and bacterial colonization exists. Details from the case
      notes of all patients seen in our institution's burns unit over a two-year period
      were recorded and the incidence of hypertrophic scarring and burn bacterial
      colonization was noted. A total of 127 scars were recorded, and of these, 51 were
      hypertrophic and 76 nonhypertrophic. The incidence of bacterial colonization in
      the hypertrophic scar group was 88%, an association that achieved significance (P
      < .05) in comparison with nonhypertrophic scars (27%). This association holds
      true for individual organisms such as Staphylococcus aureus and Escherichia coli
      and for all burn depths and healing times. This study suggests that burn wound
      bacterial colonization may be more important than previously believed and perhaps
      suggests that striving toward an aseptic burn wound environment may reduce the
      incidence of hypertrophic scarring.

PMID- 17211217
TI  - Quality assurance assessment of the use of linezolid in the treatment of thermal
      injury patients at a community teaching hospital.
AB  - We sought to evaluate the adverse effect profile of linezolid among thermal
      injury patients requiring treatment for Enterococcus species or other Gram
      positive infection warranting treatment with linezolid. Seventy-six inhalation
      injury and/or thermal injury patients experiencing 94 exposures to linezolid for
      48 hours or longer (range, 2-83 days) were included. We evaluated leukocyte count
      and platelet count for the time period preceding, during, and after therapy with
      linezolid based on specified time periods of exposure for evaluation of specific
      adverse effects. Sixty-three of 76 (83%) patient admissions were complicated by
      inhalation injury. The average TBSA involvement was 34.4% (range, 0-98%). The
      onset of thrombocytopenia before linezolid therapy was noted in 21 of 57 patients
      (36.8%), which was attributable to fluid resuscitation and acute platelet
      consumption. After they were exposure to linezolid, 12 patients developed
      thrombocytopenia. Platelet counts recovered in 7 of these 12 patients with
      continued exposure to linezolid; however, thrombocytopenia persisted for more
      than 9 days after therapy in 9 patients, of whom 6 patients succumbed to sepsis.
      On average, thrombocytes increased by 102,000/mm3 during linezolid treatment.
      Leucopenia was rare in thermal injury patients, and persisting thrombocytopenia
      in this population was associated with sepsis and mortality. Continuing linezolid
      therapy after the onset of thrombocytopenia among survivors almost always
      resulted in recovery from thrombocytopenia.

PMID- 17211219
TI  - The reliability and concurrent validity of the figure-of-eight method of
      measuring hand edema in patients with burns.
AB  - OBJECTIVE: Water volumetry is considered the "gold standard" for hand edema
      assessment. This technique requires considerable time, staff, and specialized
      equipment. The figure-of-eight method for hand edema assessment has been tested
      only in the orthopedic population. The objective of this study was to test the
      reliability and concurrent validity of the figure-of-eight method of measuring
      hand edema in the burn patient population. METHODS: We conducted a prospective
      blinded study with 20 burned patients (33 edematous hands) admitted from February
      to May 2005. Two testers performed three separate blinded measurements on each
      edematous hand, using the figure-of-eight technique. A third tester performed two
      measurements, using water volumetry. An independent investigator recorded all
      measurements. Intratester and intertester reliability were analyzed. Concurrent
      validity was examined and compared with water volumetry measurements. RESULTS:
      Intraclass correlation coefficients (ICC) for the intratester reliability of the
      figure-of-eight method were 0.96 for tester 1 and 0.97 for tester 2. The ICC for
      intertester reliability of the figure-of-eight measurements was 0.94. The
      intratester ICC for volumetric measurements was 0.99. Correlation coefficient
      (Pearson's) for tester 1 was 0.83 (P < .01), and for tester 2, 0.89 (P < .01).
      CONCLUSION: The figure-of-eight technique is a reliable and valid measurement
      tool for measuring hand edema. This technique is a more clinically feasible tool
      than water volumetry in the burn patient population.

PMID- 17211220
TI  - Which of the abbreviated burn severity index variables are having impact on the
      hospital length of stay?
AB  - Quality control is an important tool ensuring continuous medical efficacy.
      Outcome scores, however, are unfavorable from a statistical point of view, are
      not meaningful for less severely injured patients, and may put the treating
      physicians under pressure to limit therapeutic efforts. In this study the
      variables of the abbreviated burn severity index (ABSI), primarily an outcome
      score, were used to predict length of hospital stay (HLS), a continuous
      quantitative variable reflecting treatment costs and incidence of complications
      even in less severely injured patients. For 365 patients a multiple linear
      regression analysis was used to evaluate the influence of the ABSI variables on
      HLS. Among survivors, age and total body surface area burned (TBSA) contributed
      significantly to HLS, whereas for nonsurvivors only TBSA significantly influenced
      HLS. Neither gender nor presence of full-thickness burn or inhalation injury
      showed a significant influence on HLS. The impact of age and TBSA on HLS might be
      used as a benchmarking system to evaluate quality of care. However, although HLS
      is probably widely dependent on regional health care systems, TBSA and age proved
      to be the only variables of the ABSI to correlate with HLS.

PMID- 17211221
TI  - The early acute phase response after burn injury in mice.
AB  - In the hours immediately after burn injury, the body enters into an acute phase
      reaction characterized, in part, by the augmentation of cytokine and acute phase
      protein production. This reaction has been poorly characterized in the 24 hours
      immediately after injury. To better understand the early acute phase response, 8-
      to 10-week-old BALB/C female mice were subjected to a 15% total body surface area
      (TBSA). Hepatic levels of tumor necrosis factor-alpha, interleukin-1beta, and
      interleukin-6 were monitored. In addition, the circulating level of serum amyloid
      A, an acute phase protein, also was measured at the same time points. Tumor
      necrosis factor-alpha levels peaked 2 hours after burn injury, whereas
      interleukin-1beta had a biphasic response, increasing 2 hours after injury and
      again at 12 hours. Interleukin-6 and serum amyloid A were not increased until 12
      hours after injury and began to decline at 24 hours. These results demonstrate
      that within the liver, the acute phase response after burn injury initially
      involves tumor necrosis factor-alpha and interleukin-1beta, whereas interleukin-6
      is not involved until later and that systemic serum amyloid A levels are not
      increased until interleukin-6 is also increased.

PMID- 17211222
TI  - Attenuation of leukocytes sequestration by carbon monoxide-releasing molecules:
      liberated carbon monoxide in the liver of thermally injured mice.
AB  - We sought to determine whether the CO-releasing molecules, ie, liberated CO,
      attenuates the leukocytes sequestration in the liver of thermally injured mice.
      Sixty-five mice were assigned to five groups in three respective experiments. In
      each experiment, mice in sham group (n = 7) and sham + CORM-2 group (n = 7) were
      underwent sham thermal injury, whereas mice in burn group (n = 7) received 15%
      TBSA full-thickness thermal injury, mice in burn + CORM-2 group (n = 7) underwent
      the same thermal injury with the immediate administration of CORM-2 (8 mg/kg
      intravenously), and mice in burn + DMSO group (n = 7) underwent the same thermal
      injury with an immediate 160 microl-bolus injection of 0.5% dimethyl
      sulfoxide/saline. Polymorphonuclear leucocyte (PMN) accumulation (assessed by the
      myeloperoxidase assay) was assessed in mice liver. Activation of nuclear factor
      kappa B (NF-kappaB) and the expression levels of ICAM-1 and VCAM-1 in liver were
      assessed. In an in vitro experiment, sinusoidal endothelial cells (SECs) isolated
      from the liver of normal mice were stimulated by experimental mice serum (50%
      v/v) for 4 hours. Subsequently, the adhesion of PMNs to SECs was assessed. In
      addition, the number and states (rolling or stationary) of leukocytes in liver
      were observed by intravital microscopy. Treatment of thermally injured mice with
      CORM-2 attenuated PMN accumulation and prevented activation of NF-kappaB in the
      liver, which was accompanied by a decrease of the expression of ICAM-1 and VCAM
      1. In parallel, PMNs adhesion to SECs stimulated by CORM-2-treated thermally
      injured mice serum was markedly decreased. Intravital microscopy showed that the
      stationary leukocytes in thermally injured mice liver were significantly reduced
      by treatment of CORM-2. CORM-released CO attenuates leukocytes sequestration in
      the liver of burn mice by interfering with NF-kappaB activation, protein
      expression of ICAM-1 and VCAM-1, and therefore suppressing endothelial cells
      proadhesive phenotype.

PMID- 17211223
TI  - Survival and wound contraction of full-thickness skin grafts are associated with
      the degree of tissue edema of the graft bed in immediate excision and early wound
      excision and grafting in a rabbit model.
AB  - The objective of this study was to evaluate the survival of skin grafts on graft
      beds of immediate excision and early wound excision at various time periods after
      burns and to establish the appropriate timing of burn excision and grafting in a
      rabbit model. Eight groups of male Japanese white rabbits (n = 5 per group) were
      established. Animals of all groups were given a 5 x 10-cm full-thickness burn on
      their shaved back and received the autografting 3, 6, 12, 18, 24, 48, and 72
      hours and 5 days after receiving burns, respectively. Weekly skin-graft
      evaluation was performed for 5 weeks after grafting by measurement of the
      secondary skin graft contracture (in size) and the survival area of grafts, with
      use of computerized planimetry. In addition, relative quantitative analysis of
      exudation on the burned wound was evaluated. Our results indicated that the
      exudate-related graft loss and graft contracture varied according to the timing
      of wound excision. The wound contractures of the grafts were maximal in both the
      18-hour and 24-hour groups at 2, 3, 4, and 5 weeks after grafting. The 18-hour
      and 24-hour groups exhibited significantly greater graft loss than the 72-hour
      and 5-day groups (P < .05). An apparent increase in the amount of exudation on
      the graft bed was shown in the 18- and 24-hour groups vs the other groups (P <
      .05). A reverse correlation was detected between the survival area of the skin
      graft and the degree of exudation of the graft bed. In conclusion, the survival
      area and secondary contraction of skin grafts are associated with the degree of
      tissue edema of the graft bed in immediate excision and early excision in the
      rabbit model. The adverse affect of edema leakage on the graft bed for skin graft
      survival was shown. We believe that immediate excision or early wound excision
      and grafting performed within 12 hours after burn or 48 hours later should be
      considered in the rabbit model.

PMID- 17211224
TI  - Working with patients who have big burns: exploring the perspectives of senior
      medical staff of different professional groups.
AB  - This study aimed to explore the views of senior medical staff on the emotional
      impact and dilemmas of working with patients who have big burns. Six members of
      medical staff from different professional groups were interviewed: two consultant
      plastic and reconstructive surgeons, two consultant anesthetists, and two senior
      physiotherapists. Their interviews were analyzed using a qualitative methodology,
      namely interpretative phenomenological analysis. The emerging patterns were
      discussed in the light of systemic and social constructionist theory. The
      emerging themes revolved around three main areas. The participants shared their
      ideas on the tensions around decision-making and the different positions they
      take when they have to make life-or-death decisions or when they have to live
      with the consequences of these decisions taken by others. They brought to the
      discussion differing ideas about what they consider as the right emotional
      distance and emotional talk with patients. Finally, they reflected on intragroup
      ways of support generated by their burns team and they highlight the use of humor
      and the use informal networks as ways of support.

PMID- 17211225
TI  - An unusual case: burn following an accidental exposure to
      methylchloroisothiazolinone/methylisothiazolinone.

PMID- 17211226
TI  - Ecthyma gangrenosum in a patient with toxic epidermal necrolysis.
AB  - Toxic epidermal necrolysis and Stevens-Johnson syndrome are a spectrum of disease
      characterized by a delayed hypersensitivity reaction that involves the skin and
      mucous membranes and typically is associated with either recent upper respiratory
      infection or with certain medications. Ecthyma gangrenosum is a rare necrotizing
      vasculitis that most commonly affects immunocompromised and burn patients and is
      often a sequela of Pseudomonas aeruginosa bacteremia. The cutaneous lesions of
      ecthyma gangrenosum are characterized by an erythematous halo surrounding a dark
      gray or black nodule. P. aeruginosa preferentially invades the venules, resulting
      in secondary thrombosis of the arterioles, tissue edema, and separation of the
      epidermis. Management of ecthyma gangrenosum includes systemic treatment with
      antipseudomonal antibiotics and debridment of the lesions, as well as improving
      the patient's immune status if possible. We present a case of a patient admitted
      to the burn unit for toxic epidermal necrolysis who developed pseudomonal
      bacteremia with ecthyma gangrenosum.

PMID- 17211227
TI  - Calcium alginate dressing-related hypercalcemia.
AB  - To date, no adverse effects or contraindications have been observed in
      association with the use of calcium alginate dressing on an exuding wound. This
      is the first case in the literature in which it is suggested that using a large
      quantity of calcium alginate dressing could be harmful. The scenario leading to
      the complication and suggestions to prevent similar conditions in the future are
      described.

PMID- 17211228
TI  - RhoA/Rho-kinase pathway: much more than just a modulation of vascular tone.
      Evidence from studies in humans.
AB  - RhoA/Rho-kinase signaling and its relationship/balance with the nitric oxide
      level, angiotensin II and vasopressors for cardiovascular pathophysiology is of
      increasing importance, and its involvement goes far beyond blood pressure
      regulation. The deep involvement of this pathway in cardiovascular biology is now
      known to include a wide spectrum of conditions relating to the long-term
      complications of hypertension, and in general of cardiovascular pathophysiology,
      such as changes in cardiovascular structure (remodeling) and the induction of
      atherosclerosis, involvement in the pathophysiological relationships between
      inflammation and hypertension, and in those between hypertension, glucose
      metabolism and insulin resistance. Studies from our laboratory have made an
      important contribution to the understanding of the cellular and molecular
      mechanisms mediated by the RhoA/Rho-kinase pathway, which include all the aspects
      of cardiovascular pathophysiology in which this pathway plays a role. In
      addition, if it is considered that our contribution to the clarification of these
      mechanisms only comes from studies in humans, their impact on the scenario of the
      RhoA/Rho-kinase pathway's biology, essentially supported by studies 'in vitro' or
      in animal models, is immediate. This review examines all the aspects of RhoA/Rho
      kinase signaling in the light of the available data, and gives an updated and
      useful overall picture of its involvement in cardiovascular pathophysiology.

PMID- 17211229
TI  - Central blood pressures: do we need them in the management of cardiovascular
      disease? Is it a feasible therapeutic target?
AB  - It is well established that in young and healthy individuals central (aortic or
      carotid) systolic and pulse pressures are different from peripheral (brachial)
      corresponding pressures as a consequence of progressive changes in arterial
      stiffness and pressure wave reflections along the arterial tree. There is
      evidence indicating that in interventions with pharmaceutical and non
      pharmaceutical agents, central pressures are subjected to greater changes than
      peripheral pressures, and they are more closely related to the pathophysiology of
      end-organ damage or cardiovascular risk. Therefore central blood pressures may be
      of higher clinical importance than peripheral pressures. The present review aims
      to provide an insight into the (patho)physiology of central blood pressures, to
      present the most accurate techniques for their estimation, and to discuss the
      available experimental and epidemiological data that support the emerging need
      for the evaluation of central blood pressures in clinical practice.

PMID- 17211230
TI  - The higher, the better? Blood pressure after acute myocardial infarction.

PMID- 17211231
TI  - Masked hypertension: an independent predictor of organ damage.

PMID- 17211232
TI  - Genetic determinants of C-reactive protein levels in metabolic syndrome: a role
      for the adrenergic system?

PMID- 17211233
TI  - Cardiovascular risk factors: can long-term alcohol withdrawal benefit heavy
      drinkers?

PMID- 17211235
TI  - Mechanisms of benefit of sustained weight reduction in morbid obesity: beyond
      reduction in conventional cardiovascular risk factors.

PMID- 17211234
TI  - Peripheral or central augmentation index: an esoteric question or a non-invasive
      clue to central haemodynamics?

PMID- 17211236
TI  - Trends in lifestyle factors affecting blood pressure in hypertensive and
      normotensive Finns during 1982-2002.
AB  - OBJECTIVE: To assess the trends in blood pressure (BP) affecting lifestyle
      factors in hypertensive and normotensive Finns from 1982 to 2002. DESIGN AND
      SETTING: Five independent cross-sectional population surveys conducted in 1982,
      1987, 1992, 1997 and 2002 in the provinces of North Karelia and Kuopio in eastern
      Finland and the region of Turku-Loimaa in southwestern Finland. PARTICIPANTS:
      Stratified random samples of men and women aged 25-64 years were drawn from the
      national population register. The participants (n = 28 235) were classified into
      four groups according to their BP level and treatment status: normotensive,
      unaware hypertensive, aware but untreated hypertensive, and treated hypertensive
      subjects. MAIN OUTCOME MEASURES: Alcohol intake, body mass index (BMI), 24-h
      urinary sodium and potassium excretion (a subsample of 5849 subjects) and the
      proportion of subjects with leisure-time physical activity (LTPA) at least three
      times a week. RESULTS: Mean BMI increased significantly in all groups except in
      untreated hypertensive women. Alcohol intake increased in all men but especially
      in hypertensive women (P < 0.001). The 24-h urinary sodium excretion decreased
      significantly in all BP groups. The proportion of subjects with a recommended
      level of LTPA increased significantly and similarly in all BP groups (P < 0.001).
      CONCLUSIONS: The unfavourable trends observed in mean BMI and alcohol intake in
      the entire population should be reversed in order to decrease the frequency of
      hypertension in Finland. The health behaviours of hypertensive subjects should be
      carefully monitored and modified in a more systematic and efficient way than at
      present.

PMID- 17211237
TI  - Prognostic value of blood pressure measured during hospitalization after acute
      myocardial infarction: an insight from survival trials.
AB  - BACKGROUND: The prognostic value of blood pressure measured during
      hospitalization after acute myocardial infarction (MI) has not been investigated,
      particularly with regard to arrhythmic death. METHODS: A total of 3311 placebo
      patients (2612 men, median age 64 years; range 23-92) from the EMIAT, CAMIAT,
      SWORD, TRACE and DIAMOND-MI studies with left ventricular ejection fraction less
      than 40% or asymptomatic ventricular arrhythmia surviving more than 45 days after
      MI were pooled. Systolic and diastolic blood pressures and pulse pressures were
      measured soon after MI (median 6 days, range 0-53 days). Mortality up to 2 years
      was examined using Cox regression. RESULTS: At the 2-year follow-up, after
      adjustment for age, sex, smoking, previous MI, hypertension, heart rate, New York
      Heart Association functional class, baseline treatments, study effect and
      diastolic blood pressure, reduced systolic blood pressure measured during
      hospitalization after acute MI significantly increased the risk of all-cause
      mortality [hazard ratio (HR) for 10% increase in systolic blood pressure 0.80,
      95% confidence interval (CI) 0.71-0.90; P < 0.001] and arrhythmic mortality (HR
      0.73, 95% CI 0.61-0.86; P = 0.001). Reduced diastolic blood pressure
      significantly increased the risk of all-cause mortality (HR 0.87, 95% CI 0.77
      0.98; P = 0.02) and arrhythmic mortality (HR 0.80, 95% CI 0.68-0.93; P = 0.005).
      CONCLUSION: In post-MI patients with left ventricular ejection fraction less than
      40% or asymptomatic ventricular arrhythmia, reduced blood pressure measured
      during hospitalization after MI significantly predicts all-cause mortality and
      arrhythmic mortality, and can be reliably used to identify patients who are at
      risk of dying after MI.

PMID- 17211238
TI  - How reliable is isolated clinical hypertension defined by a single 24-h
      ambulatory blood pressure monitoring?
AB  - BACKGROUND: Isolated clinical hypertension (ICH) is characterized by a
      persistently elevated clinic blood pressure in the presence of a normal day-time
      or 24-h ambulatory blood pressure (ABP). This definition is based on a single ABP
      monitoring (ABPM) and little attention has been focused on the reproducibility of
      this condition. OBJECTIVE: To investigate the reliability of the criteria
      currently recommended by major hypertension guidelines to detect ICH based on a
      single 24-h ABPM session. METHODS: A total of 611 never-treated grade 1 and 2
      hypertensive patients (mean age 46 +/- 12 years) referred for the first time to
      our out-patient clinic, underwent repeated clinic blood pressure measurements,
      routine investigations, two 24-h periods of ABPM 1-4 weeks apart, cardiac and
      carotid ultrasound examinations. ABPM was always performed over a working day and
      the same daily activities were recommended during the two periods. ICH was
      diagnosed by the following criteria: (i) mean daytime values < 135/85 mmHg or
      (ii) mean 24-h blood pressure values < 125/80 mmHg during the first ABPM.
      RESULTS: The overall prevalence of ICH was 7.1% according to criterion (i) and
      5.4% according to criterion (ii). Twenty (46.6%) of the 43 patients with mean
      daytime blood pressure values < 135/85 mmHg during the first ABPM, exceeded this
      cut-off value during the second ABPM period. Twenty-two (66.6%) of the 33
      patients with mean 24-h blood pressure values < 120/80 mmHg during the first ABPM
      did not confirm a normal blood pressure profile during the second ABPM recording.
      Cardiovascular involvement was significantly lower in subjects with persistent
      normal ABP compared to those with non-reproducible ICH pattern or sustained
      hypertensives. CONCLUSIONS: These findings clearly indicate that: (i) the
      classification of ICH on the basis of a single ABPM, using the cut-offs suggested
      by major hypertension guidelines, has a limited short-term reproducibility and
      (ii) repeated ABPM recordings should be recommended to correctly diagnose
      patients with ICH and improve cardiovascular risk stratification.

PMID- 17211239
TI  - Detection of carotid atherosclerosis in individuals with masked hypertension and
      white-coat hypertension by self-measured blood pressure at home: the Ohasama
      study.
AB  - OBJECTIVE: To investigate carotid atherosclerosis in individuals with masked
      hypertension (MHT) and white-coat hypertension (WCHT) in a general population.
      METHODS: Self-measurement of blood pressure at home (HBP) and casual blood
      pressure (CBP) measurements were recorded in 812 individuals aged at least 55
      years (mean 66.4 years) from the general Japanese population. The intima-media
      thickness (IMT) of the near and far wall of both common carotid arteries was
      measured and averaged. The relationships between carotid atherosclerosis (IMT and
      plaque) and the four blood pressure groups (sustained normal blood pressure: HBP
      < 135/85 mmHg, CBP < 140/90 mmHg; WCHT: HBP < 135/85 mmHg, CBP >or= 140/90 mmHg;
      MHT: HBP >or= 135/85 mmHg, CBP < 140/90 mmHg; sustained hypertension: HBP >or=
      135/85 mmHg, CBP >or= 140/90 mmHg) were examined using multivariate analysis
      adjusted for possible confounding factors. RESULTS: Adjusted IMT in individuals
      with sustained hypertension [0.77 mm; 95% confidence interval (CI) 0.75 to 0.79
      mm] and MHT (0.77 mm; 95% CI 0.73 to 0.80 mm) was significantly greater than in
      those with sustained normal blood pressure (0.71 mm; 95% CI 0.69 to 0.72 mm) and
      WCHT (0.72 mm; 95% CI 0.71 to 0.74 mm) (P < 0.0001). The odds ratios for the
      presence of plaques in all four groups were similar to the trends in IMT.
      CONCLUSIONS: Our findings imply that CBP measurements alone are insufficient to
      distinguish individuals at high risk of carotid atherosclerosis from those at low
      risk. However, these individuals do have distinct HBP measurements, suggesting
      that HBP measurement could become a valuable tool for predicting carotid
      atherosclerosis.

PMID- 17211241
TI  - Depolarization evoked by acetylcholine in mesenteric arteries of hypertensive
      rats attenuates endothelium-dependent hyperpolarizing factor.
AB  - OBJECTIVE: During blockade of endothelium-dependent hyperpolarizing factor
      (EDHF), acetylcholine evoked larger and faster depolarization in mesenteric
      arteries of spontaneously hypertensive rats (SHR) than normotensive Wistar-Kyoto
      (WKY) rats. We studied the mechanism underlying this response and its role in the
      attenuation of EDHF. METHODS: Electrophysiology, computational modelling and
      myography were used to study changes in membrane potential and effects on
      contractility. RESULTS: The large acetylcholine-evoked depolarization in SHR was
      accompanied by contraction, but this was not seen in WKY rats. The depolarization
      depended on release of intracellular Ca2+ but was unaffected by nonselective
      cation channel inhibitors, gadolinium, lanthanum or amiloride. The depolarization
      was significantly reduced by the Ca2+-dependent Cl- channel inhibitors, niflumic
      acid or flufenamic acid, or alterations in Cl- gradients using bumetanide
      (Na/K/Cl transporter inhibitor) or external Cl- replacement with isethionate.
      These drugs altered the time course of EDHF-evoked hyperpolarizations in SHR,
      making them indistinguishable from those in WKY rats. EDHF-induced relaxation was
      less sensitive to acetylcholine in SHR than in WKY rats, but this difference was
      eliminated following artery pretreatment with bumetanide. Computational modelling
      in which the SHR fast depolarizing response was selectively modulated mimicked
      physiologically acquired results obtained in SHR and WKY rats during Cl- -channel
      blockade. CONCLUSIONS: Acetylcholine evokes a fast depolarization in SHR but not
      in WKY rats, mediated by the opening of Ca2+-dependent Cl- channels. The
      depolarization is responsible for a constriction that reduces EDHF-mediated
      relaxation. Data suggest that Ca2+-dependent Cl- channels may provide a novel
      therapeutic target for improvement of endothelial dysfunction during
      hypertension.

PMID- 17211240
TI  - C-reactive protein, an 'intermediate phenotype' for inflammation: human twin
      studies reveal heritability, association with blood pressure and the metabolic
      syndrome, and the influence of common polymorphism at catecholaminergic/beta
      adrenergic pathway loci.
AB  - BACKGROUND: C-reactive protein (CRP) both reflects and participates in
      inflammation, and its circulating concentration marks cardiovascular risk. Here
      we sought to understand the role of heredity in determining CRP secretion.
      METHODS: CRP, as well as multiple facets of the metabolic syndrome, were measured
      in a series of 229 twins, both monozygotic (MZ) and dizygotic (DZ), to estimate
      trait heritability (h2). Single nucleotide polymorphism (SNP) genotyping was done
      at adrenergic pathway loci. Haplotypes were inferred from genotypes by likelihood
      methods. Association of CRP with hypertension and the metabolic syndrome was
      studied in a larger series of 732 individuals, including 79 with hypertension.
      RESULTS: MZ and DZ twin variance components indicated substantial h2 for CRP, at
      approximately 56 +/- 7% (P < 0.001). CRP was significantly associated (P < 0.05)
      with multiple features of the metabolic syndrome in twins, including body mass
      index (BMI), blood pressure (BP), leptin and lipids. In established hypertension,
      elevated CRP was associated with increased BP, BMI, insulin, HOMA (index of
      insulin resistance), leptin, triglycerides and norepinephrine. Twin correlations
      indicated pleiotropy (shared genetic determination) for CRP with BMI (P =
      0.0002), leptin (P < 0.001), triglycerides (P = 0.002) and systolic blood
      pressure (SBP) (P = 0.042). Approximately 9800 genotypes (43 genetic variants at
      17 loci) were scored within catecholaminergic pathways: biosynthetic, receptor
      and signal transduction. Plasma CRP concentration in twins was predicted by
      polymorphisms at three loci in physiological series within the catecholamine
      biosynthetic/beta-adrenergic pathway: TH (tyrosine hydroxylase), ADRB1 (beta1
      adrenergic receptor) and ADRB2 (beta2-adrenergic receptor). In the TH promoter,
      common allelic variation accounted for up to approximately 6.6% of CRP inter
      individual variance. At ADRB1, variation at Gly389Arg predicted approximately
      2.8% of CRP, while ADRB2 promoter variants T-47C and T-20C also contributed.
      Particular haplotypes and diplotypes at TH and ADRB1 also predicted CRP, though
      typically no better than single SNPs alone. Epistasis (gene-by-gene interaction)
      was demonstrated for particular combinations of TH and ADRB2 alleles, consistent
      with their actions in a pathway in series. In an illustration of pleiotropy, not
      only CRP but also plasma triglycerides were predicted by polymorphisms at TH (P =
      0.0053) and ADRB2 (P = 0.027). CONCLUSIONS: CRP secretion is substantially
      heritable in humans, demonstrating pleiotropy (shared genetic determination) with
      other features of the metabolic syndrome, such as BMI, triglycerides or BP.
      Multiple, common genetic variants in the catecholaminergic/beta-adrenergic
      pathway contribute to CRP, and these variants (especially at TH and ADRB2) seem
      to interact (epistasis) to influence the trait. The results uncover novel
      pathophysiological links between the adrenergic system and inflammation, and
      suggest new strategies to probe the role and actions of inflammation within this
      setting.

PMID- 17211242
TI  - Ramipril dose-dependently increases nitric oxide availability in the radial
      artery of essential hypertension patients.
AB  - DESIGN AND PARTICIPANTS: A double-blind, crossover, randomized study was designed
      to evaluate the effect of 3-month treatment with a lower versus a higher
      antihypertensive dosage of ramipril (5 or 10 mg/day) on nitric oxide (NO)
      dependent vasodilation in 46 untreated patients with essential hypertension.
      Radial artery flow-mediated dilation (FMD), before and after the intra-arterial
      infusion of NG-monomethyl-L-arginine (L-NMMA), to block NO synthase, and the
      response to sublingual glyceril trinitrate (GTN, 25 microg) were measured at
      baseline and after the two treatment periods as a change in artery diameter
      (computerized system from ultrasound scans). Plasma angiotensin II and oxidative
      stress markers were also assessed. RESULTS: FMD was significantly (P < 0.01)
      lower in hypertensive patients (4.6 +/- 1.8%) than in normotensive subjects (7.1
      +/- 2.6%), whereas the response to GTN was similar. L-NMMA significantly (P <
      0.001) inhibited FMD in normotensive but not in hypertensive subjects. Mean 24-h
      ambulatory blood pressure, plasma angiotensin II and oxidative stress marker
      levels were similarly reduced at the end of the two treatment periods. Both
      dosages of ramipril significantly (P < 0.001) increased FMD (5 mg: 5.9 +/- 2.1%;
      10 mg: 6.3 +/- 2.4%) without modifying the response to GTN. However, compared
      with baseline (11 +/- 19%), the inhibiting effect of L-NMMA on FMD (NO-dependent
      FMD) was significantly (P < 0.01) greater with ramipril 10 mg (49 +/- 12%) than 5
      mg per day (38 +/- 15%). The improvement in FMD and NO-dependent FMD was not
      related to changes in plasma levels of angiotensin II or markers of oxidative
      stress. CONCLUSION: Treatment with ramipril at a higher dosage induced a greater
      improvement in NO-dependent vasodilation compared with the lower antihypertensive
      dosage in hypertensive patients.

PMID- 17211243
TI  - Endothelial dysfunction and cardiovascular risk profile in long-term withdrawing
      alcoholics.
AB  - BACKGROUND: Rates of cardiovascular morbidity and mortality are greater in heavy
      alcoholics than in either teetotallers or light-to-moderate drinkers. OBJECTIVE:
      On the assumption that factors leading to atherosclerotic damage remain operative
      even after long-term alcohol withdrawal, we studied the possible mechanisms of
      raised cardiovascular risk in former heavy alcoholics. METHODS: Forty-two
      apparently disease-free, normotensive alcoholics detoxified for 37.1 +/- 31.9
      (SD) months, median 24, participated in the study. They were compared with 39
      lifetime alcohol-abstaining control subjects, carefully matched for age, sex,
      body mass index, smoking and dietary habits, physical activity, lipids and
      fasting glucose. Endothelial function (flow-mediated dilation of brachial artery,
      high-resolution ultrasound technique), blood pressure, and some parameters of
      endothelial activation, oxidative stress, vascular inflammation and insulin
      sensitivity were measured. RESULTS: The maximal percentage of flow-mediated
      dilatation was reduced in detoxified alcoholics (10.1 +/- 4.6 versus 14.9 +/-
      7.4, P < 0.001) who also showed significantly higher blood pressure (systolic
      127.5 +/- 12.9 versus 118.2 +/- 10.7 mmHg, P < 0.001; diastolic 79.4 +/- 7.1
      versus 74.6 +/- 6.4 mmHg, P < 0.01; mean 95.4 +/- 8.2 versus 89.1 +/- 7.3 mmHg, P
      < 0.001), uric acid (5.0 +/- 1.1 versus 4.4 +/- 0.8 mg/dl, P < 0.05), high
      sensitivity C-reactive protein (2.1 +/- 2.0 versus 1.0 +/- 0.9 mg/l, P < 0.01),
      endothelin-1 (0.38 +/- 0.11 versus 0.17 +/- 0.10 pg/ml, P < 0.001) and fasting
      insulin (10.4 +/- 4.5 versus 5.6 +/- 1.6 muU/ml, P < 0.001) with abnormal
      homeostasis model assessment index of insulin resistance (2.3 +/- 1.1 versus 1.2
      +/- 0.4, P < 0.001). CONCLUSION: Previous heavy alcoholism, in spite of long-term
      withdrawal, is associated with endothelial dysfunction and a wide cluster of
      haemodynamic, vascular and metabolic abnormalities that indicate an unfavourable
      cardiovascular and metabolic risk profile even in apparently disease-free former
      alcoholics.

PMID- 17211244
TI  - Relationship between augmentation index obtained from carotid and radial artery
      pressure waveforms.
AB  - OBJECTIVE: Increased aortic and carotid arterial augmentation index (AI) has been
      directly linked with cardiovascular disease risk, mortality and morbidity. The
      aim of this study was to examine whether AI obtained directly from radial artery
      pressure waveforms (radial AI) can provide information comparable with carotid
      arterial AI measurements. METHODS: In a cross-sectional study of 204 apparently
      healthy subjects (88 men and 116 women) aged 19-76 years (51 +/- 15 years, mean
      +/- SD), carotid AI [(second peak carotid systolic pressure - first peak carotid
      systolic pressure)/carotid pulse pressure*100] and radial AI [(second peak radial
      systolic pressure - diastolic pressure)/(first peak radial systolic pressure -
      diastolic pressure)*100] were measured using applanation tonometry. RESULTS:
      Radial AI was strongly correlated with carotid AI (r = 0.86, P < 0.0001, SD of
      difference 10.0%), although radial AI was consistently approximately 66% higher
      than carotid AI. In 16 apparently healthy young adults (11 men and five women,
      aged 23 +/- 3 years) handgrip exercise was immediately followed by post-exercise
      muscle ischaemia (PEMI) to compare changes in carotid and radial AI during
      increased sympathetic nervous activity. PEMI caused parallel increases in carotid
      and radial AI (26 and 19%). Accordingly, changes in radial AI with PEMI were
      strongly correlated with corresponding changes in carotid AI (r = 0.86, P <
      0.0001, SD of difference 7.3%). CONCLUSION: These results suggest that AI
      obtained directly from radial arterial pressure waveforms could provide
      equivalent information to carotid arterial AI, and has potential as a surrogate
      marker of cardiovascular disease.

PMID- 17211245
TI  - Measurement of pulse wave velocity: site matters.
AB  - BACKGROUND: Aortic pulse wave velocity (PWV) predicts mortality from
      cardiovascular disease, ischaemic heart disease and stroke. However, a comparison
      of associations between PWV measured at different sites and atherosclerosis in
      coronary, carotid and femoral arteries has not been made. METHODS: In 159 men
      (ages 45-82 years) with and without known coronary artery disease, PWV
      measurements were made between carotid-femoral, carotid-radial and femoral
      posterior tibial sites, using an ultrasound technique. Coronary artery
      calcification (CAC) scores were measured by multislice computed tomography.
      Carotid and femoral intima-media thickness (IMT) and presence of plaque were
      determined by ultrasound. Known coronary artery disease was confirmed by
      angiography. Participants were grouped into four categories of CAC score: 0-10,
      11-100, 101-400, > 400 Hounsfield Units (HU). Measurements of blood pressure,
      heart rate and fasting bloods were made in all individuals. RESULTS: Carotid
      femoral PWV correlated positively with CAC score and increased with incremental
      coronary calcification category (median carotid-femoral PWV 16.8 m/s in those
      with CAC score > 400 HU and 13.8 m/s in those with CAC score < 10 HU; P = 0.003).
      Carotid-femoral PWV also correlated with carotid and femoral IMT (P < 0.001, P =
      0.004, respectively) and with carotid and femoral plaque (P = 0.001, P = 0.038,
      respectively). Increased carotid-femoral PWV also correlated with increasing age
      (P < 0.001), systolic blood pressure (P < 0.001), mean arterial pressure and
      pulse pressure (P < 0.001). Carotid-radial and femoral-posterior tibial PWV were
      not significantly associated with CAC score, carotid or femoral IMT or carotid
      plaque. CONCLUSIONS: Carotid-femoral PWV is a better indicator of atherosclerosis
      than either carotid-radial or femoral-posterior tibial PWV, and should be used
      preferentially in studies of atherosclerosis and in stratifying risk in clinical
      settings.

PMID- 17211246
TI  - The relationship between aortic augmentation index and pulse wave velocity: an
      invasive study.
AB  - OBJECTIVES: The aortic augmentation index (AI) and aortic pulse wave velocity
      (PWV) are known to be indicators of arterial stiffness. However, it is not clear
      whether aortic AI and PWV reflect aortic stiffness in similar ways. We
      investigated the relationship between aortic AI and PWV by measuring them
      directly using a catheter technique. DESIGN AND METHODS: Forty-one patients, aged
      34-79 years, were studied during diagnostic cardiac catheterization. Aortic
      pressures were measured using a catheter-tip manometer at two points, one in the
      ascending aorta and one 40 cm distally in the descending aorta. Aortic AI was
      defined as the difference between early and late pressure peaks divided by the
      pulse pressure of the ascending aorta. Aortic PWV was calculated as the distance
      between the two measuring sites divided by the transit time. We also examined the
      effects of vasodilatation on AI and PWV by the intra-aortic administration of
      nitroglycerin in 15 patients. RESULTS: AI was significantly related to age,
      systolic aortic pressure, heart rate, left ventricular ejection time, and height.
      Aortic PWV showed an association only with age and systolic aortic pressure.
      There was no significant relationship between aortic AI and PWV (r = 0.28, NS).
      Nitroglycerin also produced different effects on aortic AI and PWV: aortic AI was
      significantly decreased (-0.17, P < 0.01) after nitroglycerin, but PWV remained
      unchanged (+0.4 m/s, NS). CONCLUSIONS: Aortic AI and PWV cannot be used
      interchangeably as an index of arterial stiffness. AI may not be a true indicator
      of arterial stiffness, but an index of wave reflection including PWV.

PMID- 17211247
TI  - Pressor response induced by central angiotensin II is mediated by activation of
      Rho/Rho-kinase pathway via AT1 receptors.
AB  - OBJECTIVES: The brain renin-angiotensin system plays an important role in
      cardiovascular regulation and the pathogenesis of hypertension. Angiotensin II
      activates the Rho/Rho-kinase pathway in vascular smooth muscle cells and
      cardiomyocytes in vitro. The aim of the present study was to determine whether
      angiotensin II in the brainstem activates the Rho/Rho-kinase pathway, and, if so,
      whether this mechanism is involved in the central pressor action of angiotensin
      II. METHODS AND RESULTS: Angiotensin II infused intracisternally for 7 days in
      Wistar-Kyoto rats (WKY) increased systolic blood pressure (SBP) and urinary
      norepinephrine excretion. These responses were abolished by the co-infusion of Y
      27632, a specific Rho-kinase inhibitor, or valsartan. The intracisternal infusion
      of Y-27632 or valsartan also reduced SBP and norepinephrine excretion in
      spontaneously hypertensive rats (SHR). Western blot analysis was performed to
      examine the expression levels of membranous RhoA and phosphorylated ezrin,
      radixin, and moesin (p-ERM), which reflects Rho/Rho-kinase activity. The
      expression levels of membranous RhoA and p-ERM in the brainstem were
      significantly greater in both angiotensin II-treated WKY and SHR than in vehicle
      treated WKY. Valsartan reduced the expression levels of membranous RhoA and p-ERM
      in angiotensin II-treated WKY and SHR. Y-27632 reduced the expression levels of p
      ERM in angiotensin II-treated WKY and SHR. CONCLUSIONS: These results suggest
      that the pressor response induced by intracisternally infused angiotensin II is
      substantially mediated by the activation of the Rho/Rho-kinase pathway via AT1
      receptors of the brainstem in WKY, and that this pathway might be involved in the
      hypertensive mechanisms of SHR.

PMID- 17211248
TI  - Effect of oestrogen on reactive oxygen species production in the aortas of
      ovariectomized Dahl salt-sensitive rats.
AB  - OBJECTIVE: In the present study, we examined whether ovariectomy increases
      reactive oxygen species (ROS) and the expression of nicotinamide adenine
      dinucleotide phosphate, reduced form (NADPH) oxidase and modulates the scavenger
      enzymes for ROS in the aortas of Dahl salt-sensitive (DSS) rats fed a high salt
      diet. METHODS: DSS female rats were ovariectomized and fed a high salt diet (8%
      NaCl), or a high salt diet plus oestrogen supplement for 4 weeks. Urinary levels
      of hydrogen peroxide (H2O2) were measured by using 2',7'-dichlorofluorescein. The
      expression of an NADPH oxidase subunit p22phox, extracellular superoxide
      dismutase (ecSOD), glutathione peroxidase (GPx)1, GPx4 and monocyte
      chemoattractant protein 1 (MCP-1) messenger RNA was assessed by reverse
      transcription-polymerase chain reaction. The expression of MCP-1, and macrophage
      infiltration were examined by immunohistochemical analysis. RESULTS: Ovariectomy
      increased superoxide production and the expression of NADPH oxidase subunit
      p22phox mRNA and protein in the aortas of DSS rats fed a high salt diet. In
      contrast, ovariectomy reduced the expression of ecSOD mRNA and protein and the
      expression of GPx1 and GPx4 mRNA in the aorta. Ovariectomy increased MCP-1 mRNA
      and protein expression and ED1-positive cells in the aorta. CONCLUSIONS:
      Ovariectomy leads to an amplification of oxidative stress in DSS rats fed a high
      salt diet synergistically by an increase in the ROS-generating system and a
      decrease in the ROS-eliminating system, as shown in the increase in superoxide
      production and the urinary excretion of H2O2. Oestrogen supplementation
      counteracted these alterations, showing how oestrogen is antioxidative.

PMID- 17211249
TI  - Increased oxidative stress impairs endothelial modulation of contractions in
      arteries from spontaneously hypertensive rats.
AB  - OBJECTIVES: The endothelium modulates vascular contractions. We investigated the
      effects of oxidative stress on endothelial modulation of contractions in
      hypertension. METHODS: Changes in isometric tension of femoral arterial rings
      from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were recorded.
      RESULTS: The contractile response to norepinephrine of arteries with endothelium
      was greater in SHR than in WKY rats (P < 0.0001). Endothelium removal augmented
      the norepinephrine-induced contraction (P < 0.05). The augmentation was more
      pronounced in WKY than in SHR, which resulted in comparable contraction of
      arteries without endothelium in both strains. Nomega-nitro-L-arginine methyl
      ester (100 micromol/l) mimicked the effect of endothelium removal. Production of
      nitric oxide (NO, assessed by measuring nitrite/nitrate concentrations) during
      the contraction was not different between SHR and WKY. Vitamin C suppressed the
      contraction of arteries with endothelium from SHR but not from WKY (P < 0.05).
      Diphenyleneiodonium and apocynin, inhibitors of nicotinamide adenine
      dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase,
      attenuated the contraction of arteries with endothelium from SHR (P < 0.001) but
      not WKY, but did not affect contractions induced by serotonin. Superoxide
      generated by xanthine oxidase/hypoxanthine enhanced the norepinephrine-induced
      contraction of arteries with endothelium from WKY (P < 0.0001), and this effect
      was reversed by vitamin C. CONCLUSIONS: In rat femoral arteries, NO released from
      the endothelium modulates vascular contraction. In SHR, production of superoxide
      by NADH/NADPH oxidase, which may be activated by norepinephrine, is enhanced,
      resulting in the inactivation of NO and impairment of endothelial modulation of
      vascular contractions. Vascular oxidative stress may contribute to the altered
      circulation in hypertension by impairing endothelial modulation of vascular
      contractions.

PMID- 17211250
TI  - C-reactive protein and intercellular adhesion molecule-1 are stronger predictors
      of oxidant stress than blood pressure in established hypertension.
AB  - BACKGROUND: Oxidant stress is implicated in the pathogenesis of atherosclerosis
      in cardiovascular diseases. Our aim was to test oxidative stress, as 8-iso
      prostaglandin F2alpha (8-iso-PGF2alpha), and its relationship with inflammation
      markers C-reactive protein (CRP) and tumour necrosis factor-alpha (TNFalpha), and
      endothelial activation assayed as soluble intercellular adhesion molecule (ICAM)
      1 and vascular cell adhesion molecule (VCAM)-1 in essential hypertension.
      METHODS: In 216 essential hypertensive patients and 55 healthy control
      individuals, plasma levels of high-sensitivity CRP and TNFalpha, 8-iso-PGF2alpha,
      ICAM-1 and VCAM-1 were measured in basal conditions. Moreover, basal and 24-h
      ambulatory blood pressure monitoring measurements were obtained. RESULTS:
      Essential hypertensive patients showed higher levels of 8-iso-PGF2alpha (P <
      0.0001), high-sensitivity CRP, TNFalpha, ICAM-1 and VCAM-1 (P < 0.001,
      respectively) than control individuals. In control individuals, 8-iso-PGF2alpha
      correlated only with high-sensitivity CRP (P < 0.001). In essential hypertensive
      patients, 8-iso-PGF2alpha correlated with high-sensitivity CRP (P < 0.000001),
      TNFalpha (P < 0.0001), ICAM-1 (P < 0.000001), VCAM-1 (P < 0.0001) and blood
      pressure. The multiple regression analysis considering 8-iso-PGF2alpha as the
      dependent variable showed that in essential hypertensive patients the independent
      predictors of 8-iso-PGF2alpha were ICAM-1, high-sensitivity CRP (P < 0.00001,
      respectively), and TNFalpha (P = 0.028). CONCLUSION: Our findings demonstrate
      that oxidant stress is increased in essential hypertension, and relates to
      inflammation and endothelial activation. Factors other than blood pressure are
      stronger predictors of oxidant stress.

PMID- 17211251
TI  - Neonatal streptozotocin-induced glucose intolerance: different consequences in
      Lyon normotensive and hypertensive rats.
AB  - BACKGROUND: Lyon hypertensive (LH) rats exhibit a mild hypertension associated
      with excessive body weight, spontaneous hyperlipidemia, elevated insulin/glucose
      ratio and exaggerated urinary protein excretion. AIMS: We aimed to develop, in LH
      rats and their normotensive control (LL) rats, a moderate non-insulin-dependent
      diabetic model to study the different consequences on metabolic and renal
      functions. METHODS: Non-insulin-dependent diabetes was induced by intraperitoneal
      injection of streptozotocin (STZ) at 2 days of age (50, 75 or 100 mg/kg for LH
      and 75, 100 or 125 mg/kg for LL rats). The evolution, with age, of glycemia,
      glucose tolerance (glucose 2 g/kg by gavage), blood pressure, plasma lipids and
      urinary protein and albumin excretions were studied in control and STZ-treated LH
      and LL rats. RESULTS: Although fasting glycemia was not significantly changed,
      the neonatal administration of STZ increased non-fasting glycemia and induced a
      marked glucose intolerance that were comparable between LH rats receiving 75
      mg/kg and LL rats receiving 100 mg/kg of STZ. Interestingly, in treated LH rats
      only, the impaired glucose tolerance was accompanied by further metabolic and
      renal dysfunctions characterized by additional increases in plasma cholesterol
      (+28%) and triglycerides (+105%) and accelerated progression of proteinuria
      (+36%) and albuminuria (+48%). CONCLUSIONS: These observations indicate that
      susceptibility to diabetic metabolic disorders and renal diseases may be linked
      to the genetic predisposition to hypertension. This new model offers a reasonable
      reflection of the human situation, where hypertension and non-insulin-dependent
      diabetes often coincide, suitable for molecular, biochemical and pharmacological
      investigations.

PMID- 17211252
TI  - Weight loss after bariatric surgery improves aortic elastic properties and left
      ventricular function in individuals with morbid obesity: a 3-year follow-up
      study.
AB  - OBJECTIVE: To investigate whether weight loss after bariatric surgery (gastric
      bypass) is associated with changes in aortic function (an important determinant
      of left ventricular function) and in left ventricular function, in morbidly obese
      individuals 3 and 36 months after surgery. METHODS: We used echocardiography to
      evaluate 60 obese individuals [body mass index (BMI) > 40 kg/m2] who underwent
      surgery and 20 obese individuals who neither underwent surgery nor lost weight,
      at baseline and at 3 and 36 months of follow-up, and 40 lean individuals (BMI <
      25 kg/m2) of similar age, sex and risk factors, at baseline. We measured aortic
      strain, distensibility, stiffness index, pressure-strain modulus and Doppler
      indices of left ventricular diastolic dysfunction (ratio of peak early to peak
      atrial flow velocities, isovolumic relaxation time and deceleration time).
      RESULTS: Baseline aortic function and Doppler diastolic indices were impaired in
      obese individuals compared with those who were lean (P < 0.05). During 3 and 36
      months of follow-up, BMI and left ventricular diastolic diameter, volume, mass
      and wall thickness were reduced, and indices of aortic function and left
      ventricular diastolic function were normalized, in obese individuals after
      surgery [aortic distensibility (cm2 x dyn(-1) x 10(-6)): 1.9 before surgery, 3.4
      at 3 months after surgery and 4.3 at 3 years after surgery, compared with 3.36 in
      lean controls; P < 0.01], but not in those who did not lose weight. The reduction
      in BMI after surgery was related to the concomitant improvement in indices of
      aortic function (P < 0.01) and isovolumic relaxation time (P < 0.05) after
      adjustment for age, sex and concomitant reduction in blood pressure, lipids and
      glucose concentrations. CONCLUSION: Weight reduction after bariatric surgery
      normalizes aortic function, reduces left ventricular hypertrophy and, thus,
      improves left ventricular diastolic function in morbidly obese individuals over a
      3-year period of follow-up.

PMID- 17211253
TI  - Adenosine A1 receptor expression during the transition from compensated pressure
      overload hypertrophy to heart failure.
AB  - OBJECTIVES: Myocardial adenosine is increased in pressure-overload hypertrophy
      (POH) and exerts important cardioprotective effects that delay transition to left
      ventricular failure. Adenosine-mediated signaling is attenuated in POH, but
      whether this depends on receptor or postreceptor defects is unknown. We therefore
      examined left ventricular adenosine A1-receptor gene and protein expression in
      experimental POH. METHODS: Six week-old Sprague-Dawley rats were subjected to
      abdominal aortic banding (group B) or sham operation (group S). Echocardiography
      and left ventricular catheterization were performed 10 weeks later under ketamine
      anesthesia. Left ventricular and lung weight indices were obtained postmortem. A1
      Receptor mRNA and protein expression were measured in samples from left
      ventricular, right ventricular and aortic arch tissue. Group B rats were
      subgrouped as having compensated or decompensated hypertrophy according to the
      absence or presence of lung congestion (lung weight index below or above mean +/-
      2SD compared with group S rats). RESULTS: Both mRNA and protein A1-receptor
      expression were significantly increased in compensated group B versus group S
      rats (by, respectively, 37 and 77%; both P < 0.01). This was not observed in
      decompensated group B rats. No consistent gene or receptor expression changes
      were observed in right ventricular or aortic tissues. CONCLUSIONS: In compensated
      POH, increased interstitial adenosine concentrations are accompanied by increased
      expression of the specific receptor mediating the major cardioprotective effects
      of this autacoid. Such overexpression is no longer detectable once the transition
      from POH to left ventricular failure has occurred. These observations may have
      pathophysiological and, in perspective, therapeutic relevance to the course of
      hypertensive heart disease.

PMID- 17211254
TI  - Therapeutic effects of angiotensin II type 1 receptor blocker at an advanced
      stage of hypertensive diastolic heart failure.
AB  - OBJECTIVE: Angiotensin II type 1 receptor blocker (ARB) is increasingly
      prescribed for the treatment of systolic heart failure with a growing body of
      clinical evidence. The roles of ARB, however, remain to be clarified in the
      treatment of diastolic heart failure (DHF), particularly at its advanced stage.
      This experimental study investigated the effects of ARB administered at an
      advanced stage of hypertensive DHF. METHODS: Dahl salt-sensitive rats fed an 8%
      NaCl diet from age 7 weeks represent overt DHF at age 20 weeks, as noted in
      previous studies (hypertensive DHF model). The DHF model rats were randomly
      divided into two groups at age 17 weeks when left ventricular diastolic
      dysfunction, hypertrophy, fibrosis, macrophage infiltration and reactive oxygen
      species generation were already augmented; six rats treated for 3 weeks with a
      subdepressor dose of ARB (olmesartan 0.6 mg/kg per day), and six untreated rats.
      RESULTS: The 3-week administration of ARB significantly decreased the left
      ventricular end-diastolic pressure in association with attenuation of left
      ventricular hypertrophy, fibrosis and diastolic dysfunction. Macrophage
      infiltration was attenuated with decreased gene expression of transforming growth
      factor-beta1 and monocyte chemoattractant protein-1 in the left ventricular
      myocardium of the ARB-treated rats. The production of reactive oxygen species
      also decreased with NADPH oxidase activity. CONCLUSIONS: ARB provides beneficial
      effects in hypertensive DHF independent of its antihypertensive effects even if
      initiated at an advanced stage. The beneficial effects are at least partly
      attributed to the attenuation of inflammatory changes and oxidative stress
      through the suppression of cytokine and chemokine production and of NADPH oxidase
      activity.

PMID- 17211255
TI  - Left ventricular hypertrophy is present in one-half of newly-diagnosed peripheral
      arterial disease patients.
AB  - OBJECTIVES: Peripheral arterial disease (PAD) patients are at high risk of
      cardiac death. Coincidental but silent coronary disease is obviously a major
      contributor but left ventricular hypertrophy (LVH) could be a second major
      contributor. METHODS: To investigate whether LVH could really be making a large
      contribution to cardiac death in PAD, we assessed the prevalence of LVH when PAD
      was first diagnosed. RESULTS: The prevalence of echo LVH when left ventricular
      mass was indexed to body surface area was 50%. Although office blood pressure and
      24-h blood pressure were both significantly higher in those with LVH, in clinical
      practice, a contemporaneous blood pressure measurement (office or 24 h) at the
      time of PAD diagnosis would only partially identify those with LVH. For example,
      an office blood pressure cut-off of < 140/90 mmHg was found in 27% of all LVH
      cases and a 24-h blood pressure cut-off of < 125/80 mmHg was found in 24% of all
      LVH cases. CONCLUSION: In conclusion, there is already a high prevalence of LVH
      in patients at first diagnosis of PAD. LVH is therefore common enough in PAD
      patients to potentially make a major contribution to cardiac death, which means
      that future research should now investigate whether screening for and regressing
      LVH when present would actually reduce cardiac deaths over and above merely
      achieving target blood pressure.

PMID- 17211256
TI  - Effects of growth hormone and insulin-like growth factor-1 on cardiac hypertrophy
      of hypertensive patients.
AB  - OBJECTIVES: Growth hormone (GH) and insulin-like growth factor-1 (IGF-1)
      interfere with cardiac mass (left ventricular mass; LVM) development. We
      investigated the role of the GH/IGF-1 axis on LVM and ventricular geometry in a
      group of 230 never-treated hypertensive patients. METHODS: Partition values for
      left ventricular hypertrophy (LVH) were 125 g/m2 for both women and men. Insulin
      resistance was estimated by the homeostasis model assessment (HOMA) index.
      RESULTS: A significant inverse correlation was observed between IGF-1 and both
      fasting insulin (r = -0.249; P < 0.0001) and GH (r = -0.218; P < 0.0001).
      Systolic blood pressure (157.3 +/- 13.6 versus 149.4 +/- 12.8 mmHg; P < 0.001),
      fasting insulin (17.4 +/- 8.5 versus 11.4 +/- 6.0 microU/l; P < 0.0001), HOMA
      (4.4 +/- 2.3 versus 2.9 +/- 1.6; P < 0.0001) and GH (1.0 +/- 1.0 versus 0.4 +/-
      0.5 ng/ml; P < 0.0001) were significantly higher in patients with LVH; on the
      contrary, IGF-1 values (119.1 +/- 47.8 versus 160.1 +/- 75.5 ng/ml; P < 0.0001)
      were higher in patients without LVH. In a logistic regression analysis, the
      strongest independent predictors of LVH were GH [relative risk (RR) = 2.078; 95%
      confidence interval (CI) = 1.364-3.163], HOMA (RR = 1.345; 95% CI = 1.133-1.596),
      IGF-1 (RR = 0.993; 95% CI = 0.998-0.999) and systolic blood pressure (RR = 1.036;
      95% CI = 1.013-1.060). IGF-1 showed an opposite trend in patients with eccentric
      and concentric hypertrophy. CONCLUSIONS: Present data demonstrate that the
      increase in LVM prevalent in human essential hypertension is directly associated
      with serum GH levels and inversely related to circulating IGF-1.

PMID- 17211258
TI  - Diurnal variability of hazards.

PMID- 17211259
TI  - To stimulate or not to stimulate: is adrenocorticotrophic hormone testing
      necessary, or not?

PMID- 17211261
TI  - CAQ: Orthopaedic Trauma "Damage Control".

PMID- 17211263
TI  - The use of negative-pressure wound therapy (NPWT) in the temporary treatment of
      soft-tissue injuries associated with high-energy open tibial shaft fractures.
AB  - OBJECTIVES: To evaluate the utility of negative-pressure wound therapy (NPWT) in
      the setting of high-energy open tibial shaft fractures. DESIGN, SETTING, AND
      PATIENTS/PARTICIPANTS: This was a retrospective consecutive series in a level 1
      university-based trauma center. Forty-nine consecutive patients presenting to a
      level 1 trauma center between 1996 and 2004 with 50 grade/type III open tibial
      shaft fractures were assessed. INTERVENTION: The open wounds associated with each
      fracture were each treated with NPWT before definitive wound closure or coverage.
      MAIN OUTCOME MEASUREMENTS: Infection rate, need for amputation after attempted
      definitive coverage, problems with bony healing requiring surgical intervention,
      reoperation rate after definitive coverage, and the type of definitive coverage
      required. RESULTS: The overall infection rate for all grade/type III open
      fractures was 15 of 50 fractures (30%), with 11 of 50 (22%) requiring repeated
      surgery for infection. The infection rate was 12.5% for grade/type IIIA open
      fractures, 45.8% for grade/type IIIB, and 50% for grade/type IIIC. Twenty-four of
      50 fractures (48%) required subsequent surgery to facilitate fracture healing.
      Five fractures required amputation after attempted coverage. Seven of 24
      fractures initially classified as grade/type IIIA and 10 of 24 fractures
      initially classified as grade/type IIIB ultimately required free tissue transfer
      or rotational muscle flap coverage. CONCLUSIONS: Infection and nonunion rates
      with the use of NPWT for temporary coverage of wounds associated with grade/type
      III open tibial shaft fractures are similar to those of historical controls, but
      this technique may be beneficial in decreasing the need for free tissue transfer
      or rotational muscle flap coverage.

PMID- 17211262
TI  - Operative treatment of 109 tibial plateau fractures: five- to 27-year follow-up
      results.
AB  - OBJECTIVE: To analyze the long-term (5-27 years) functional and radiologic
      results of surgically treated fractures of the tibial plateau. DESIGN:
      Retrospective study. SETTING: University hospital. PATIENTS AND METHODS: Two
      hundred two consecutive tibial plateau fractures were included in this study. All
      fractures were classified according to both the AO and the Schatzker
      classification. There were 112 men and 90 women. The mean age at injury was 46
      years (16 to 88). One hundred sixty-three patients had isolated fractures and 39
      had multiple fractures. A 1 year follow-up was done in all 202 patients. One
      hundred nine of these patients also had an additional long-term follow-up visit.
      Functional results of these 109 patients were graded with the Neer- and HSS-knee
      scores. Radiologic results were graded with the Ahlback score. Statistical
      analysis was performed by means of the SPSS data analysis program. RESULTS: An
      uneventful union was present at the 1 year follow-up in 95% of the patients,
      along with a mean knee ROM of 130 degrees (range, 10-145 degrees). One hundred
      nine patients had a long-term follow-up visit after a mean period of 14 years
      (range, 5-27 years). The mean ROM at this time was 135 degrees (range, 0-145
      degrees). Functional results showed a mean Neer score of 88.6 points (range, 56
      100 points) and a mean HSS score of 84.8 points (range, 19-100 points).
      Monocondylar fractures showed statistically significant better functional results
      compared to bicondylar fractures. In 31% of the patients, secondary
      osteoarthritis had developed but was well tolerated in most (64% of the
      patients). Patients with a malalignment of more then 5 degrees developed a
      moderate to severe grade of osteoarthritis statistically significant more often
      (27% of the patients) compared to patients with an anatomic knee axis (9.2%; MWU,
      P = 0.02). Age did not appear to have any influence on the results. CONCLUSION:
      Long-term results after open reduction and internal fixation for tibial plateau
      fractures are excellent, independent of the patient's age.

PMID- 17211264
TI  - Functional outcome in treatment of unstable trochanteric and subtrochanteric
      fractures with the proximal femoral nail and the Medoff sliding plate.
AB  - OBJECTIVE: To compare outcome between the proximal femoral nail (PFN) and the
      Medoff sliding plate (MSP) in patients with unstable trochanteric or
      subtrochanteric fractures. METHODS: This was a consecutive prospective randomized
      clinical study. In all, 203 patients admitted to two university hospitals with an
      unstable trochanteric or a subtrochanteric fracture type were included. Surgery
      was performed with a short intramedullary nail or a dual-sliding plate device.
      Follow up visits occurred at 6 weeks, 4 months, and 12 months. Functional outcome
      was measured by walking ability, rising from a chair, curb test, and additional
      assessments of abductor strength, pain, living conditions, and complications.
      RESULTS: The ability to walk 15 m at 6 weeks was significantly better in the PFN
      group compared to the MSP group with an odds ratio 2.2 (P = 0.04, 95% confidence
      limits 1.03-4.67). No statistical difference in walking ability could be found
      between trochanteric and subtrochanteric fractures. The major complication rate
      (8% in the PFN group and 4% in the MSP group) did not differ statistically (P =
      0.50) but reoperations were more frequent in the PFN group (9%) compared to the
      MSP group (1%; P < 0.02). CONCLUSIONS: There were no major differences in
      functional outcome or major complications between the treatment groups. Reasons
      other than the operated fracture seem to be equally important in determining the
      long-term functional ability of the patients in our study. An advantage with the
      MSP was the lower reoperation rate.

PMID- 17211265
TI  - Efficacy of warfarin reversal in orthopedic trauma surgery patients.
AB  - OBJECTIVES: We determine the efficacy of active reversal of warfarin
      anticoagulation with intravenous vitamin K compared to withholding warfarin in
      patients requiring urgent orthopedic trauma surgery. DESIGN: This was a
      prospective cohort with immediate prehypothesis consecutive retrospective
      comparative case series conducted at a level 1 university hospital trauma unit.
      PATIENTS: Forty-eight consecutive patients between 1998 and 2004 in a study
      composed of a prospective cohort were compared with a retrospective consecutive
      case series of warfarinized orthopedic trauma patients requiring urgent surgery.
      The prospective arm directly followed the historic case series from which the
      hypothesis was generated. INTERVENTION: Vitamin K administration. MAIN OUTCOME
      MEASURES: Primary outcome was time to surgery. Secondary outcomes were problems
      with active reversal, length of time for warfarin stabilization after surgery,
      and complications. RESULTS: The mean time to surgery in warfarinized patients not
      given vitamin K was 111.9 hours; in the intervention group, it was 67.4 hours,
      giving a mean difference of 44.5 hours (P = 0.01). Vitamin K reduced the
      international normalized ratio (INR) to less than 2.0 in 74% of patients within
      24 hours. There were no complications of vitamin K administration. A dose of
      vitamin K costs approximately 1/1000 of a hospital bed day cost. A loading dose
      of warfarin on the second postoperative day took approximately 1 day longer to
      reach an INR of greater than 2.0 in the intervention patients than in those who
      had not been given vitamin K. CONCLUSIONS: Warfarin reversal with vitamin K was
      successful and facilitated earlier surgery in all patients; the first dose was
      effective in approximately three quarters of patients. It is cost-effective, with
      no side effects caused in this study.

PMID- 17211266
TI  - Early predictors of mortality in hemodynamically unstable pelvis fractures.
AB  - OBJECTIVES: To determine reliable, early indicators of mortality and causes of
      death in hemodynamically unstable patients with pelvic ring injuries. DESIGN:
      This was a retrospective review of a prospective pelvic database. METHODS: In
      all, 187 hemodynamically unstable patients with pelvic fractures (persistent
      systolic blood pressure <90 mm Hg after receiving 2 L of intravenous crystalloid)
      admitted from April 1998 to November 2004 were included. Intervention was Level 1
      Trauma Center-Pelvis Fracture standardized protocol. Main outcome measurements
      were: Injury Severity Score (ISS), Revised Trauma Score (RTS), age, blood
      transfusion, mortality, and multisystem organ failure (MOF). RESULTS: Group 1 (39
      patients) did not survive their injury. Group 2 (148 patients) survived their
      injury. Fracture pattern (chi(2) = 9.1, P = 0.33), and treatment with
      angiography/embolization (chi(2) = 0.054, P = 0.84) were not predictive of death.
      Patients requiring more blood had a statistically significant higher mortality
      rate. The ISS (t = -5.62, P < 0.001), RTS (t = 6.10, P < 0.001), age >60 years
      old (chi(2) = 5.4, P = 0.03), and transfusion (t = -2.70, P = 0.010) were
      statistically significant independent predictors of mortality. A logistic
      regression analysis and receiver operating characteristic curves indicated that
      of these variables, RTS was the most predictive independent variable. However, a
      model including all four variables was superior at predicting mortality. Most
      deaths were attributed to exsanguination (74.4%) or MOF (17.9%). CONCLUSIONS:
      Predictors of mortality in pelvis fracture patients should be available early in
      the course of treatment in order to be useful. Death within 24 hours was most
      often a result of acute blood loss while death after 24 hours was most often
      caused by MOF. Improved survival will depend upon the evolution of early
      hemorrhage control and resuscitative strategies in patients at high mortality
      risk.

PMID- 17211267
TI  - A cadaver study of the trochanteric pelvic clamp for pelvic reduction.
AB  - OBJECTIVE: The purpose of this study is to evaluate the ability of the
      trochanteric pelvic clamp to reduce anterior-posterior compression pelvic ring
      disruptions. DESIGN: Eight fresh-frozen cadavers underwent sequential disruption
      of the pelvic ring to represent both anterior-posterior compression type II (APC
      II) and anterior-posterior compression type III (APC III) injury patterns.
      Reduction with the trochanteric pelvic clamp was performed. Prereduction and
      postreduction anterior/posterior pelvic displacements were determined
      radiographically. SETTING: Institutional research laboratory. INTERVENTION:
      Application of a trochanteric pelvic clamp to reduce a pelvic ring disruption.
      MAIN OUTCOME MEASURE: Radiographic measurements of anterior and posterior pelvic
      displacement were evaluated and compared to similar values after reduction with
      the trochanteric pelvic clamp. RESULTS: The application of the trochanteric
      pelvic clamp to simulated APC II and APC III pelvic injuries in a cadaver model
      demonstrated a significant reduction of the anterior pubic diastasis and the
      posterior disruption of the sacroiliac joint. Anterior pelvic vertical
      displacement did not improve with application of the trochanteric pelvic clamp.
      Measurement of symphysis diastasis for APC II injuries was 4.07 cm (+/-0.31)
      prereduction and 0.38 cm (+/-0.18) postreduction, (P < 0.001); for APC III
      injuries, 6.32 cm (+/-0.84) prereduction and 1.24 cm (+/-1.01) postreduction, (P
      < 0.001). For posterior sacroiliac disruptions, APC II injury measurements were
      1.81 cm (+/-0.35) prereduction and 0.69 cm (+/-0.32) postreduction (P < 0.001);
      for APC III injuries, 3.81 cm (+/-1.06) prereduction and 1.86 cm (+/-0.82)
      postreduction (P = 0.002). At the symphysis pubis, APC II vertical displacement
      was 0.32 cm (+/-0.36) prereduction and 0.30 cm (+/-0.38) postreduction (P <
      0.740); for APC III injuries, 0.5 cm (+/-0.31) prereduction and 0.88 cm (+/-0.53)
      postreduction (P < 0.098). CONCLUSIONS: The application of the trochanteric
      pelvic clamp is reliable for obtaining reduction of anterior-posterior
      compression pelvic injuries in a cadaver model.

PMID- 17211268
TI  - Biomechanical analysis of distal femur fracture fixation: fixed-angle screw-plate
      construct versus condylar blade plate.
AB  - OBJECTIVE: The objective of this study is to establish the relative strength of
      fixation of a locking distal femoral plate compared with the condylar blade
      plate. METHODS: Eight matched pairs of fresh-frozen cadaveric femurs were
      selected and evaluated for bone density. A gap osteotomy model was used to
      simulate an OTA/AO A3 comminuted distal femur fracture. One femur of each pair
      was fixed with the blade plate; the other, with a locking plate. After 100 N
      preload and 10,000 cycles between 100 N and 1000 N, total displacement of each
      specimen was assessed. After completion of cyclic loading, maximum load to
      failure was tested. RESULTS: Significantly greater subsidence (total axial
      displacement) occurred with the blade plate (1.70 +/- 0.45 mm; range, 1.21-2.48
      mm) than with the locking plate fixation (1.04 +/- 0.33 mm; range, 0.67-1.60 mm)
      after cyclic loading (P = 0.03). In load-to-failure testing, force absorbed by
      the locking plate before failure (9085 +/- 1585 N; range, 7269-11,850 N) was
      significantly greater than the load tolerated by the blade plate construct (5591
      +/- 945 N; range, 3546-6684 N; P = 0.001). Variability in bone mineral density
      did not affect the findings (fixed angle distal femoral plate r = 0.1563;
      condylar blade plate r = 0.0796). CONCLUSIONS: The locking screw-plate construct
      proved stronger than the blade plate in both cyclic loading and ultimate strength
      in biomechanical testing of a simulated A3 distal femur fracture. Although
      differences were small, the biomechanical performance of the locking plate
      construct over the blade plate may lend credence to use of the locking plate
      versus the blade plate in the fixation of comminuted distal femur fractures.

PMID- 17211269
TI  - Comminuted talar neck fractures: a mechanical comparison of fixation techniques.
AB  - OBJECTIVE: To compare the mechanical performance of 3 fixation techniques for
      comminuted talar neck fractures. DESIGN: In vitro biomechanical study. SETTING:
      Bioengineering research laboratory. PARTICIPANTS: Thirty previously frozen human
      cadaveric tali were osteotomized across the talar neck. A wedge of bone 2 cm long
      and extending 50% of the medial to lateral and superior to inferior dimension of
      the talus was removed to create an unstable, comminuted fracture. INTERVENTION:
      The specimens were randomized to one of 3 fixation groups. The first group was
      fixed with 3 anterior-to-posterior screws. The second group was fixed with 2
      cannulated screws inserted from posterior to anterior. The third group was fixed
      with 1 screw from anterior to posterior and a medially applied blade plate.
      Specimens were embedded in acrylic cement and mounted on an Instron mechanical
      testing machine. Loading was applied in the dorsal-medial direction to failure.
      MAIN OUTCOME MEASURES: For each specimen, the load-displacement curve, yield
      point, and 3 mm displacement point were recorded in response to controlled dorsal
      medial loading to failure. Stiffness was calculated as the linear portion of the
      slope of the load (kN) versus displacement (mm) curve. Statistical analysis of
      the data was conducted using analysis of variance. RESULTS: The mean yield point
      of each of the fixation techniques tested exceeded 1.4 kN. No statistically
      significant difference was found between the fixation methods, even when
      variations in age and sex were considered. CONCLUSIONS: The mean yield point of
      the fixation techniques tested exceeds the theoretical stress across the talar
      neck during active motion. Anterior plate fixation provided equivalent stability
      to posterior screw fixation.

PMID- 17211270
TI  - Prolonged thromboprophylaxis with dalteparin after surgical treatment of achilles
      tendon rupture: a randomized, placebo-controlled study.
AB  - OBJECTIVES: Prophylaxis against thromboembolic complications has become routine
      after major orthopedic surgery. In contrast, it remains an issue for debate
      whether prophylaxis after minor surgery and immobilization is necessary, even
      though these treatments are well-known risk factors for deep-vein thrombosis
      (DVT). The objective of this study was to evaluate the efficacy of dalteparin
      during lower-limb immobilization after surgical treatment of Achilles tendon
      rupture. DESIGN SETTING, AND PATIENTS: Randomized, placebo-controlled, double
      blind study of 105 consecutive patients surgically treated for Achilles tendon
      rupture in a trauma hospital. DVT screening with color duplex sonography was
      conducted 3 weeks and 6 weeks after surgery. All DVTs were confirmed with
      phlebography. Intervention was placebo or dalteparin (5000 U) given
      subcutaneously once daily for 6 weeks postoperatively. MAIN OUTCOME MEASURE: DVT
      incidence. RESULTS: Primary endpoint analysis was available for 91 patients. DVT
      was diagnosed in 16 of 47 patients (34%) in the dalteparin group and in 16 of 44
      patients (36%) in the placebo group. These figures are not significantly
      different (P = 0.8). Proximal DVT was diagnosed in 1 patient (2%) in the
      dalteparin group and in 3 patients (6%) in the placebo group (P = 0.6). No
      pulmonary emboli or major bleeding occurred in either of the groups. CONCLUSIONS:
      DVT is common after surgical treatment of Achilles tendon rupture, and therefore
      effective thromboprophylaxis is desirable. In our study, thromboprophylaxis with
      dalteparin, however, does not affect the incidence of DVT during immobilization
      after Achilles tendon rupture surgery. Long-term effects of immobilization, such
      as the risk for postthrombotic syndrome, need to be investigated further.

PMID- 17211271
TI  - Plate fixation of olecranon osteotomies.
AB  - The management of intra-articular distal humeral fractures remains a difficult
      surgical problem. Although an olecranon osteotomy provides excellent exposure for
      management of these fractures, a number of complications can occur after the
      creation and repair of the osteotomy including nonunion, malunion, hardware
      failure, and pain secondary to prominent hardware. In an effort to reduce the
      incidence of these complications, the senior authors now use contoured 3.5 mm
      reconstruction plates for the fixation of their apex-distal chevron olecranon
      osteotomies. Two surgeons at a single institution used this technique of exposure
      on a series of 17 consecutive patients with intra-articular distal humerus
      fractures between 1996 and 1999. In this series, all osteotomies united. There
      was one complication related specifically to the osteotomy: one of the screws in
      the plate penetrated the proximal radioulnar joint, interfering with forearm
      rotation; a second procedure was required to shorten the screw. Only one of the
      17 patients requested plate removal during the 32 month (average) follow-up
      period. Plate fixation of olecranon osteotomies using a 3.5 mm reconstruction
      plate provides a construct with predictable healing and few complications. The
      overall results using this technique are comparable with other reported methods
      in the literature.

PMID- 17211272
TI  - Stacked plating for metadiaphyseal fractures of the distal radius: a technique
      report.
AB  - Combined injuries of the distal radius and shaft are rare, are usually caused by
      high energy, and pose a surgical dilemma. Surgical tactics and implants that are
      routinely used either for isolated fractures of the distal radius or for
      fractures of the radial shaft are often not applicable for this combined injury.
      We describe a technique of dual-stacked plating for these metadiaphyseal
      fractures and its use in two patients.

PMID- 17211273
TI  - Open tibia fracture: amputation versus limb salvage. Opinion: below-the-knee
      amputation.

PMID- 17211274
TI  - Open tibia fracture: amputation versus limb salvage. OPINION: limb salvage.

PMID- 17211275
TI  - Complex limb salvage or early amputation for severe lower-limb injury: a meta
      analysis of observational studies.
AB  - PURPOSE: Leg threatening injuries present patients and clinicians with a
      difficult decision: whether to pursue primary amputation or limb salvage? The
      purpose of our study was to review the literature in an effort to inform this
      management decision. METHODS: We systematically searched and selected
      observational studies that reported on individuals presenting with leg
      threatening injuries comparing outcomes of limb salvage versus primary
      amputation. We searched MEDLINE, CINAHL, and EMBASE. We reported on the following
      outcomes, and pooled data across trials when possible: length of hospital stay,
      total rehabilitation time, cost, clinical outcomes, failure rate for limb
      salvage, function & quality of life, pain, return to work, factors associated
      with poor outcome, and patient preference. RESULTS: Nine observational studies
      contributed data to our systematic review. The current evidence suggests that
      while length of hospital stay is similar for limb salvage and primary amputation,
      length of rehabilitation and total costs are higher for limb salvage patients.
      Salvage patients requires greater additional surgery and are significantly more
      likely to undergo re-hospitalization. Long-term functional outcomes (up to 7
      years post injury) are equivalent between limb salvage and primary amputation;
      both forms of management are associated with high rates of self-reported
      disability (40%; to 50%;), and functional status continues to worsen over time.
      Report of pain following limb salvage or primary amputation is similar. Return to
      work is essentially the same between limb salvage and primary amputation groups,
      with approximately half of such patients returning to competitive employment at 2
      years post injury. Both clinical and psychosocial factors are associated with
      poorer functional outcomes. At the time of injury patients prefer limb salvage,
      but the majority of failed salvage patients would opt for early amputation if
      they could decide again. CONCLUSION AND SIGNIFICANCE: Functional outcome among
      patients who present with leg-threatening injuries are not significantly
      different, at least up to 7 years, whether they are managed with limb salvage or
      primary amputation. Research to optimize triage decisions to avoid failed limb
      salvage as well as on interventions targeting important psychosocial prognostic
      variables should be considered a priority.

PMID- 17211276
TI  - Comparison of a technique using a new percutaneous osteosynthesis device with
      conventional open surgery for displaced patella fractures.

PMID- 17211278
TI  - Reduction and pinning of pediatric supracondylar humerus fractures in the prone
      position.

PMID- 17211280
TI  - Persistence of lamivudine-sensitive HIV-1 quasispecies in the presence of
      lamivudine in vitro and in vivo.
AB  - The establishment of persistent infection is one of the major obstacles facing
      the eradication of HIV-1. To improve our understanding of the mechanisms of viral
      persistence, we investigated the fate of defined viral quasispecies under
      conditions that might favor their eradication. We retrospectively analyzed
      changes in viral populations in HIV-1-infected patients treated with
      zidovudine/lamivudine and subsequently failing therapy within months in the years
      1996 to 1997. Furthermore, we developed an in vitro model based on simultaneous
      infection of T cells with 2 or more different viral variants. Changes in minority
      quasispecies of drug-sensitive and drug-resistant HIV-1 variants based on
      lamivudine and the corresponding lamivudine-resistant viruses carrying the M184I
      or M184V mutation were investigated using an allele-specific real-time polymerase
      chain reaction assay. We demonstrate that lamivudine-sensitive and lamivudine
      resistant HIV-1 variants are able to persist despite highly unfavorable
      conditions in vivo and in vitro and that selective advantages of viral variants
      can vary depending on the complexity of other simultaneously replicating viral
      variants.

PMID- 17211281
TI  - Two and a half years of routine HIV testing in Botswana.
AB  - BACKGROUND: Botswana was the first African country to introduce routine HIV
      testing (RHT). OBJECTIVE: To report program data for the first 2.5 years of RHT.
      METHODS: RHT was introduced in 2004. Rapid HIV tests were introduced later the
      same year and are widely available. The main criteria for RHT are symptoms of
      HIV/AIDS, pregnancy, sexually transmitted infection, and attendance for medical
      examination. Testing may also be self-initiated. FINDINGS: There has been a rapid
      scale-up of RHT. A total of 60,846 persons were tested through RHT in 2004 versus
      157,894 in 2005 and 88,218 in the first half of 2006. Testing rates in the
      population through RHT were 40 per 1000 persons, 93 per 1000 persons, and 104 per
      1000 persons, respectively. In 2005, 89% of those offered testing accepted, with
      69% of those tested being female and 31% male. The proportion of men who tested
      HIV-positive was 34% versus 30% for women. The main reasons for testing in 2005
      were patient's wish (50%), pregnancy (25%), medical examination (7%), clinical
      suspicion (6%), and sexually transmitted infection (2%). Attendance at voluntary
      counseling and testing centers has increased parallel to the scale-up of RHT.
      CONCLUSIONS: RHT has been widely accepted by the population, and no adverse
      effects or instances have been reported. It has provided increased access to
      preventive services and earlier assessment for antiretroviral treatment. We
      believe the benefits of RHT clearly outweigh the risks.

PMID- 17211282
TI  - Evaluating liver fibrosis progression and the impact of antiretroviral therapy in
      HIV and hepatitis C coinfection using a noninvasive marker.
AB  - The effects of highly active antiretroviral therapy (HAART) on progression of
      hepatic fibrosis in hepatitis C virus (HCV) coinfection with HIV are not well
      understood and are difficult to measure because of the need for repeated liver
      biopsy. We evaluated the evolution of a noninvasive measure of liver fibrosis,
      the alanine aspartyl transferase (AST)-to-platelet ratio index (APRI),
      longitudinally and determined its predictive value for hepatic outcomes in HIV
      positive patients with and without HCV coinfection. A total of 673 HIV-positive
      patients without liver complications at baseline (540 with HIV only, 133 with HIV
      HCV coinfection) were followed between 1991 and 2004 for a median of 4.6 years
      (3524 person-years). At baseline, HIV-HCV coinfection had a higher median APRI
      compared with HIV infection alone (0.59 vs. 0.33; P < 0.0001). The natural
      logarithm of the APRI [ln(APRI)] changed significantly over time, particularly
      among patients with HIV-HCV coinfection. The baseline ln(APRI) was predictive of
      liver complications (hazard ratio [HR] = 4.0, 95% confidence interval [CI]: 2.5
      to 6.4 per log), as was HCV (HR = 4.5, 95% CI: 1.5 to 14). Cumulative HAART did
      not protect against liver complications, although it was significantly associated
      with progression of APRI scores in HIV-HCV coinfection and in HIV alone. In
      conclusion, the APRI may be a useful marker for longitudinal evaluation of the
      progression of liver disease in HIV-HCV coinfection.

PMID- 17211283
TI  - Granulocyte-monocyte colony-stimulating factor upregulates HIV-1 replication in
      monocyte-derived macrophages cultured at low density.
AB  - The effects that granulocyte-monocyte colony-stimulating factor (GM-CSF) has on
      HIV-1 replication in monocyte-derived macrophage are controversial. We noted that
      groups reporting that GM-CSF inhibits HIV-1 replication performed their
      experiments at relatively high cell densities. To address this issue, we
      performed experiments at different macrophage densities. In cultures seeded at
      low cell densities, we find that adding GM-CSF during the first week of culture
      (ie, before infection, during maturation) increased viral replication compared
      with that in untreated controls in 10 of 11 donors with quantifiable HIV-1
      replication. (No effects were observed if GM-CSF was added after the first week
      of culture.) In cultures seeded at the higher cell densities representative of
      those in some previous studies, adding GM-CSF during the first week reduced
      subsequent viral replication in 8 of 12 donors. In all cases in which GM-CSF
      reduced viral replication, however, the pH in the wells containing GM-CSF-treated
      cells dropped dramatically. Macrophages in these acidified cultures had numerous
      dark granules, suggesting that they were under stress. We conclude, contrary to
      previous reports, that GM-CSF usually enhances viral replication when cells are
      grown at low densities in which excessive medium acidification can be prevented.
      Our results illustrate the dramatic effects that in vitro tissue culture
      conditions can have when studying the effect of cytokines on HIV-1 replication.

PMID- 17211285
TI  - WITHDRAWN: Management of Congenital Incudostapedial Anomalies in Stapes Surgery.
AB  - OBJECTIVES:: The management of developmental anomalies of the ossicular chain and
      otic capsule in stapes surgery tests the otologist's diagnostic skills and
      flexibility in technique and prosthesis choice. Although congenital malleus
      fixation and perilymph gusher are important clinical entities that have received
      considerable attention in the otolaryngology literature, congenital anomalies of
      the incus and stapes are less well described, can often be subtle, and have a
      distinct influence on management choice and hearing outcome. STUDY DESIGN AND
      PATIENTS:: A review of more than 200 stapes procedures yielded eight cases of
      identified congenital anomalies of the stapes or incudostapedial complex
      including congenital absence of the oval window with malformed incus and stapes,
      columellar-type stapes with promontory fixation, stapes superstructure fixation
      to the fallopian canal, and malformed incus with stapes superstructure fixation
      to the promontory. The developmental anatomy and surgical technique in each case
      are reviewed and hearing outcome is presented. RESULTS:: The surgical technique
      used in each case varied depending on the nuances of the ossicular anomaly and
      whether both the stapes and incus were affected. All eight ears (seven patients)
      that underwent a stapes procedure for either an isolated congenital stapes
      anomaly or a combined incudostapedial anomaly had a favorable hearing outcome
      with seven ears improving to within 10-dB and one ear to within 13-dB air-bone
      gap on postoperative audiometry. CONCLUSION:: Despite unanticipated findings of
      congenital anomalies of the stapes and incus during middle ear exploration for
      conductive hearing loss, a flexible management approach can lead to successful
      hearing outcomes.

PMID- 17211286
TI  - Protection against cisplatin-induced ototoxicity by adeno-associated virus
      mediated delivery of the X-linked inhibitor of apoptosis protein is not dependent
      on caspase inhibition.
AB  - HYPOTHESIS: Gene therapy with an adeno-associated viral (AAV) vector encoding the
      X-linked inhibitor of apoptosis protein (XIAP) in an animal model of cisplatin
      induced ototoxicity can elucidate apoptotic pathways in the inner ear.
      BACKGROUND: Cisplatin is limited clinically by ototoxicity associated with
      apoptosis in the inner ear. The relevant intracellular apoptotic pathways,
      however, are unknown. XIAP is an antiapoptotic protein that both inhibits
      caspases and reciprocally regulates the proapoptotic Smac/Omi proteins. AAV
      mediated delivery of various XIAP mutants could distinguish between these
      antiapoptotic pathways in the ear and further the development of specific
      reagents for gene therapy- mediated prevention of cisplatin-induced ototoxicity.
      METHODS: We administered unilaterally through the round-window AAV-harboring
      genes encoding wild-type dXIAP, yellow fluorescent protein, or either of two
      dXIAP point mutants-one deficient in caspase inhibition (dXIAP-d) and the other
      additionally deficient in the binding of Smac/Omi (dXIAP-t). All rats received a
      3-day systemic course of cisplatin. Functional hearing loss was measured by
      shifts in auditory brainstem response (ABR) thresholds after cisplatin treatment,
      and hair-cell loss was assessed by whole-mount phalloidin staining of cochlear
      turns. RESULTS: Uninjected ears universally displayed high-frequency-specific
      hair-cell loss and ABR threshold shifts upon cisplatin treatment. Although yellow
      fluorescent protein had no effect, ears injected with dXIAP exhibited 68% less
      ABR threshold shift at 32 kHz and 50% less basal-turn outer-hair-cell loss
      compared with contralateral untreated ears. This protection was maintained in
      ears injected with dXIAP-d but was abolished in those expressing dXIAP-t, which
      is incapable of blocking Smac/Omi. CONCLUSION: Hair-cell apoptosis induced by
      cisplatin involves the Smac/Omi pathway. Thus, gene therapy with either wild-type
      dXIAP or Smac/Omi-selective dXIAP-d may be effective to protect against cisplatin
      mediated ototoxicity.

PMID- 17211287
TI  - 20 years after methylprednisolone/chlorambucil treatment in idiopathic membranous
      nephropathy stage II-III with nephrotic syndrome.
AB  - There is now controlled evidence that a 6-month course with methylprednisolone
      and chlorambucil may favour remission of the nephrotic syndrome and may
      significantly improve the 10-year kidney survival in patients with idiopathic
      membranous nephropathy. We analyzed the outcome of 15 nephrotic patients
      (proteinuria 7.06 +/- 1.07 g/d), stage II-III membranous nephropathy, aged 37.93
      +/- 2.32, 8 males and 7 females, with normal serum creatinine (62.8 +/- 2.34
      micromol/l), followed > 10 years after the treatment. It consisted of 1g i.v.
      methylprednisolone for three consecutive days, followed by oral steroids 0.4
      mg/kg/d and chlorambucil 0.2 mg/kg/d monthly, alternatively. 10 patients, age and
      sex matched, who refused any treatment of any reason, represented the control
      group. Complete remission was defined as protein loss of 0.2 g/d, partial 0.2-2
      g/d with normal creatinine and renal dysfunction as increase in plasma
      creatinine. The follow-up period was between 10 and 20 years. Complete remission
      after the treatment was noted in 9/15, partial in 4/15, and 2/15 patients did not
      respond. 10-year survival rate of the whole group was 100%, 15-year - 86.7%, i.e.
      two patients with persistent nephrotic syndrome developed end-stage renal failure
      after 12 years. 13/15 patients (complete, partial remission) were followed > 15
      years without development of end-stage renal failure. One patient (female, 32)
      developed idiopathic thrombocytopenia after 8 years. 3 patients (complete
      remission) were followed > 20 years, they are still without proteinuria. 10-year
      survival rate of untreated patients was 40%. It is concluded that in nephrotic
      patients with stage II-III membranous nephropathy steroids/chlorambucil therapy
      may be effective in favoring remission and in preserving renal function.

PMID- 17211288
TI  - IgA nephropathy: 23 years of follow-up.
AB  - IgA nephropathy (IgAN) is the most common primary glomerulonephritis. Some
      patients reach end-stage renal failure (ESRF), others experience an indolent
      course. We aimed the study to examine the association of risk factors with the
      progression to renal failure. Eighty patients diagnosed with IgAN by renal biopsy
      (RB) were studied. Baseline clinical and demographic data were reviewed. Severity
      of histological involvement was scored as H. S. Lee's grading system. The mean
      age of patients at biopsy was 36.65 +/- 8.83 years with predominance of men (male
      : female, 58 : 22). Patients were followed-up from 6 months to 23 years (276
      months). An end-point was defined as the date when patient underwent their first
      haemodialysis or their last visit of follow-up. The differences in means between
      groups were compared by independent samples t-tests or one-way analysis of
      variance (ANOVA). Kaplan-Meier survival curves and Cox regression models were
      used to analyze the time course from renal biopsy to end points. The largest
      subclasses were grade I and II, with 31 patient each. Subclass III was observed
      in 12 patents. Subclass IV and V were found in 3 patients each. During the follow
      up period, all patients with grade IV and V (after 6-48 months), five patients
      grade I (after 60-144 months), four patients grade II (after 48-84 months), and 7
      patients from grade III (after 24-108 months) entered ESRD. Mean prioteinuria was
      1.68 +/- 0.99 g/day. Macrohematuria had 32; microhematuria had 48 pts. The mean
      serum creatinine was 148.02 +/- 68.76 micromol/l. By multivariate analysis using
      the Cox regression model, grades, renal insufficiency and significant proteinuria
      were independent prognostic factors for progressive renal disease. At the end of
      follow-up, grades were significantly related to serum creatinine, proteinuria,
      hypertension and progressive renal disease. Renal biopsy in IgAN may be the most
      powerful predictor for renal outcome.

PMID- 17211289
TI  - Early mortality rate in end-stage renal disease patients initiating hemodialysis.
AB  - Early referral of patients with chronic renal failure (CRF) to a nephrologist
      improves morbidity and delays mortality after start of renal replacement therapy
      (RRT). Late referral is associated with increased cardiovascular morbidity and
      short-term mortality. The aim of this study was to assess the factors associated
      with early mortality rate in ESRD patients, during the first month after
      initiating hemodialysis. One hundred and eighty nine 189 patients hospitalized at
      the Department of Nephrology in Skopje after starting RRT and followed up during
      the first month were included in this study. Early referrals were considered
      those who had been referred to a nephrologist for more than 3 months before
      initiating RRT. Female to male ratio was 93 to 96 (49/51%). Out of them, 110 were
      late referrals, and 79 early ones (58/42%). Out of 189, 20 patients died during
      the first month of follow up (10.6%). 85% of the patients who died were late
      referrals, not having time and opportunity to be treated for renal anemia, for
      malnutrition and prevention of cardiovascular and uraemic complications, and all
      of them lacked permanent vascular access. Early mortality was also associated
      with older age, renal anemia and malnutrition. Late referrals were also older,
      predominantly male and had higher serum potassium levels. The main causes of
      death were related to uraemic intoxication, malnutrition and inflammation as well
      as lack of permanent vascular access, all of it leading to sepsis, and
      cardiovascular complications.

PMID- 17211290
TI  - Differences in renal registries between the Balkans and Western Europe.
AB  - The epidemiology data of renal replacement therapy are collected by national
      renal registries and extended to international registries as the European Renal
      Association Renal Registry. The extent and accuracy of data vary widely among
      countries. The aim of this study was to compare combined data from the national
      renal registries of Balkan countries contributing the ERA-EDTA Registry or from
      other sources, with combined data from renal registries of the Western and
      Northern European Countries and regions contributing the ERA-EDTA Registry. Data
      regarding incident and prevalent patients in 2003, mean age of incident and
      prevalent patients, incidence and prevalence by cause of renal failure and
      prevalence by established therapy were compared between the countries of the
      Balkan region and the countries of Western and Northern Europe contributing to
      the ERA-EDTA Registry. Data were obtained by the Annual Report 2003 of the ERA
      EDTA Registry, and for Romania by the study of G. Mirescu published in NDT 2004.
      Some data were obtained by the questionarries sent to people responsible for the
      national registries. The results showed the following: the incident number of
      patients per million population (pmp) at day 1 of RRT, as well as at day 91,
      adjusted for age and gender, did not statistically differ between the Balkans and
      Western Europe: 119.2 +/-25.1 vs. 123.3 +/- 25.9 and 110.9 +/- 34.7 vs. 106.5 +/-
      18.3, respectively. The mean age of incident patients at day 91 of RRT
      significantly differed between the Balkans and Western Europe, 57.7 +/- 4.49 vs.
      63.3 +/- 2.2, p < 0.005. The percentage of incident patients by cause of renal
      failure at day 91 of RRT did not significantly differ between the Balkans and
      Europe. The mean incidence of the percentage of DM as a cause of renal failure
      between the Balkans and Western Europe did not differ, 23.05+/- 4.5 vs. 20.3 +/-
      7.2. When adjusted for age and gender, the significant difference in prevalent
      number of ESRD patients between the Balkans and Western Europe disappeared. The
      mean age of prevalent patients between the Balkans and Europe did not
      significantly differ, 54.3 +/- 4.2 vs. 58.2 +/- 2.8. The percentage of primary
      renal disease in prevalent patients did not significantly differ, except for
      policystic kidney disease which is significantly more frequent in Western Europe
      compared to the Balkans, 9.2 +/- 1.9 vs. 6.8 +/- 1.8, p < 0.01. Diabetes mellitus
      and hypertensive nephropathy are much more frequent in incident patients compared
      to prevalent ones. Transplantation is significantly more frequent in Western
      Europe, predominantly cadaveric, whereas dialysis is more frequent in the
      Balkans. It can be concluded that no difference exists between the incidence and
      prevalence of diabetes mellitus as a primary renal disease in ESRD patients
      between the Balkan and European countries, indicating that the epidemic of
      diabetes is already present in the Balkans and imposing, perhaps, efforts to be
      undertaken for planning prevention strategies; kidney transplantation is
      significantly less represented as RRT in Balkan countries compared to Western and
      Northern Europe, and efforts should be made for its increase, particularly the
      cadaveric one, and moreover, because the population on RRT is significantly
      younger in the Balkans.

PMID- 17211291
TI  - Preservation of the vegetative pelvic nerves and local reccurence in the
      operative treatment of rectal cancer.
AB  - Life quality of the patients operated from rectal cancer is a serious problem.
      Despite the curing as a primary objective in the treatment of the rectal cancer,
      special attention is paid to the life quality upon the performed operation on the
      subjected patients. The analyzed series consists of 29 patients with rectal
      cancer, operated on at the Digestive Surgery Clinic within the framework of the
      Clinical Centre in Skopje, in the period between 2001-2006. Our series involves
      patients from the T2 and T3 stage of the illness, where it possible to preserve
      the vegetative pelvic nerves, that are characterized by a relatively long-lasting
      symptomatology and relatively high percentage of lymphatic metastases. The
      standardization of the operative intervention resulted in an increase in the
      number of patients with continuous operations and preservation of the neuro
      vegetative plexus without influencing the radicalism of the intervention. The
      application of the Stapler and Double Stapler technique brought about an increase
      in the number of continuous operations characterized by a termino-terminal
      colorectal anastomosis. On the other hand the preventive creation of LOOP
      ileostomies in the case of the ultra low resections resulted in a decrease in the
      level of dehiscence of this type as one of the most common and most difficult
      complications. The preservation of the pelvic neuro-vegetative plexus prolongs
      the operation time by 30 to 60 minutes, depending on the case and the patient. We
      assume that the procedure does not have a particular influence on the frequency
      of the complications, and at the same time it positively affects the revival of
      the urinal and sexual function. Taking into consideration the fact that the
      lymphatic dissection increases the possibility of removal of the malignant tissue
      and enables an adequate "staging" and on the other hand the preservation of the
      pelvic plexus improves the quality of life, both in terms of the sexual function
      and the function of the urinary bladder, it is recommended that this way of
      treatment becomes an integral part in the surgical treatment of the rectal
      cancer.

PMID- 17211292
TI  - Expression of c-KIT oncoprotein in gastrointestinal stromal tumors in adults and
      children: guideline for diagnosis and treatment.
AB  - Gastrointestinal stromal tumors (GISTs) represent a distinct oncogenetic entity
      that is now center stage in clinical trials of kinase-targeted therapies. These
      neoplasms express the c-KIT oncoprotein and occur predominantly in adults, more
      rarely in children. Two selected cases of GIST expressing c-KIT, including one
      adult patient and a 9-year-old boy are presented. The adult patient was admitted
      for palpable abdominal mass without other clinical symptoms. On biopsies obtained
      by scanner-guided procedure, diagnosis of ganglioneurinoma was proposed with the
      remark that GIST tumor could not be categorically excluded. At surgery,
      voluminous encapsulated tumor located at the jejunal wall was found and totally
      excised. The second patient presented with acute upper gastrointestinal
      hemorrhage associated with several months history of general fatigue and loss of
      appetite. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a
      tumoral mass arising from the lesser curvature of the stomach compatible with
      GIST. Two small metastatic lesions in the liver were also detected. Combined
      treatment by surgery and systemic therapy by the tyrosine kinase inhibitor
      imatinib mesylate was applied.

PMID- 17211293
TI  - Radiofrequency current catheter ablation of accessory atrioventricular pathways.
AB  - BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of
      a radiofrequency catheter ablation in the patients with the Wolff-Parkinson-White
      syndrome or paroxysmal supraventricular tachycardia involving a concealed
      accessory atrio ventricular connection. METHODS AND RESULTS: During a 45 month
      period (1st January 2002 until 30th September 2005) 373 consecutive patients
      underwent electrophysiological study in our electrophysiological lab at the
      Institute for Heart Diseases. Of all the patients 171 (45.8%) were ablated for
      junction depend tachycardia. Ninety-five patients had undergone ablation of
      atrioventricular nodal reentrant tachycardia (AVNRT), atrioventricular reentry
      tachycardia (AVRT) with accessory pathway (AP) 76 patients. Ablation of the
      atrioventricular node (AVN) was performed in 59 patients, because of uncontrolled
      atrial fibrillation with implantation of pacemakers. Ablation was successful in
      206 patients (89.3%), partial successful was achieved in 21 patient (9.4%), and
      no successful only in 3 patients (1.3%). Ablation successful outcome rate was
      98.7% (without clinical supraventricular arrhythmia in the follow up period until
      September 2005). There was a need for performing a re-do ablation in 11 patients
      (4.8%). A complication occurred in 8 patients, 4.9% (only one major complication,
      complete atrioventricular block with narrow QRS complex in the AVNRT group). In
      the group with accessory pathways (atrio ventricular reentry tachycardia (AVRT),
      there were 76 patients, 28 without delta way on the electrocardiogram (concealed
      accessory pathways), 47 patients were with open form of accessory pathways, with
      delta way on EKG (Wolff-Parkinson-White syndrome) and only in one patient with
      accessory pathway between right atrio and right bundle branch (Mahaim form of
      concealed accessory pathway). In two patients with AVRT, another circle movement
      tachycardia was found after the ablation of the accessory pathways, bystander
      arrhythmia of AVNRT: CONCLUSIONS: The success and safety of catheter accessory
      pathway ablation is so great that we recommend this nonpharmacological approach
      as an initial option to any patient with AVRT who has recurrent symptomatic
      arrhythmias.

PMID- 17211294
TI  - Risk factors for development of critical limb ischemia -- a survey of diabetic
      vs. nondiabetic population.
AB  - The aim of this study is to identify the risk factors for development of chronic
      critical limb ischemia (CLI) in diabetic and nondiabetic patients with peripheral
      arterial disease (PAD). 127 patients (pts) with PAD (63 with type 2 diabetes and
      64 nondiabetic) were randomly included in a cross sectional study. Out of them 17
      were with CLI. Population was investigated for age, height, weight, sex, duration
      of PAD and diabetes, arterial hypertension, hyperlipidemia, smoking, obesity,
      systolic blood pressure, value of ankle-brachial index, previous claudicating
      distance and peripheral intervention, amputation, medical treatment with
      prostanoids, insulin and antiplatelet drugs and histories of cerebrovascular
      disease, coronary artery disease and other concomitant diseases. After adjudging
      linear correlation between mentioned variables and presence of CLI, logistic
      regression model was built. There were no significant differences in demographic
      data between both populations. Hyperlipidemia was more frequent in nondiabetic
      population. Multiple regression model show ankle-brachial index < 0,5, measured
      in previous 1-3 years (OR 3.39 CI 95% 0.28-40.78), microvascular complication
      retinopathy (OR 12.98 CI 95% 1.76-95.58), heart failure (OR 1.91 CI 95% 0.29
      2.72) and previous prostanoids treatment (OR 15.92 CI 95% 0.53-476.58) as
      predictors of development of CLI in diabetic population with PAD. After heart
      failure exclusion of model of nondiabetic pts, previous surgery (OR 3.14 CI 95%
      0.61-16.09) and smoking (OR 0.35 CI 95% 0.78-1.62) were presented as prognostic
      factors for CLI's onset. Our results indicate differences between predictors of
      CLI's onset in diabetic and nondiabetic population with PAD. Presence of
      retinopathy, previous measured ankle-brachial index and prostanoids treatment are
      predictors of development of CLI in diabetic population. Previous surgery is
      independent predictor for CLI'onset in nondiabetics. Treating concomitant heart
      failure for both populations and modifying risk factor smoking in nondiabetic
      population, have an important clinical usefulness in risk assessment approach of
      peripheral arterial disease patients.

PMID- 17211295
TI  - Predictors of in-hospital morbidity and mortality in patients with coronary
      artery disease treated with coronary artery bypass surgery.
AB  - AIM OF THE STUDY: The aim of our study was to identify markers that can predict
      early morbidity and mortality in patients with coronary artery disease who
      underwent coronary artery bypass surgery (CABG) for myocardial revascularization.
      MATERIAL AND METHODS: 749 patients (pts) were enrolled in the study at mean age
      55 +/- 8 years, 639 male and 119 female. We analyzed pre-operative demographic,
      clinical, left ventricular morphologic and functional and angiographic variables,
      per-operative characteristics, and we registered occurrence of hospital
      complications including cardiac death during the first 30 days after the
      operation. RESULTS: Hospital complications were registered in 173 (23.1%)
      patients, including cardiac death registered in two (3%) patients during the
      first 30 days after the operation. The most common complications were:
      pericardial effusion (8.4%), supraventricular arrhythmias (6.3%) and pleural
      effusion (5.6%), followed by more serious complications like infections, acute
      renal failure and stroke. Advanced age (>or=65 years), coexisting morbidities and
      risk factors: cerebrovascular disease (CVD), peripheral vascular disease (PVD),
      chronic obstructive pulmonary disease (COPD), hypertension (HTA), previous
      myocardial infarction (MI), heart failure before the operation, extensive
      coronary artery disease (CAD) (angiographicly identified), low left ventricular
      ejection fraction (LVEF), and high WMSS index were identified as predictors of in
      hospital morbidity. Advanced age, Mod Gensini score (as marker of angiographic
      severity of CAD) and WMSS index were found to be independent predictors of in
      hospital morbidity, while advanced age, heart failure before CABG and in-hospital
      complications were found to be independent predictors of in-hospital mortality.
      CONCLUSION: In patients with coronary artery disease who underwent CABG surgery,
      preoperative variables and operative technique can predict occurrence of in
      hospital morbidity, while early complications can strongly predict in-hospital
      mortality.

PMID- 17211296
TI  - Effects of ozone on the nasal mucosa (epithelial cells).
AB  - Ozone is a significant public health concern worldwide. Despite increasing
      evidence for the role of the bronchial epithelial cells in the generation of
      proinflammatory cytokines there is little information on the biological relevance
      of ozone induced release of cytokines in nasal airway inflammation. We have
      investigated the effect of ozone on the nasal mucosa using immunohistochemical
      staining of nasal biopsies taken 6h after exposure to either 400 ppb ozone or
      filtered. We found that ozone significantly increases the number of neutrophils
      in the epithelium (p=0.03), and expression of NF-kB (p<0.03), TNF-a (p<0.05), IL
      1b (p<0.03), IL-8 (p<0.007), IL-6 (p<0.02), GM-CSF (p<0.02) and ICAM-1 (p <0.01)
      in the epithelial cells 6h after exposure. Furthermore, we found a significant
      correlations between IL-8 expression and number of neutrophils (r=0.85, p< 0.002)
      and NF-kB and TNF-a expression (r=0.77, p<0.009) in the epithelium. These results
      suggest that ozone-induced inflammation of the nasal mucosa may be a consequence
      of increased synthesis and release of epithelial cell-derived cytokines and
      adhesion molecules which influence the activity of inflammatory cells.

PMID- 17211297
TI  - Prognostic value of immunoglobulin variable heavy chain gene mutation status:
      long term follow-up in a series of chronic lymphocytic leukemia patients.
AB  - B-cell chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease,
      with many patients surviving for decades with minimal or no treatment, whereas
      others succumb rapidly to their disease despite therapy. Classical staging
      systems and laboratory features help predict survival in CLL, but they do not
      distinguish patients who will progress from those whose disease will remain
      indolent. In recent years, new molecular prognostic factors have emerged that
      have significantly improved prediction of the risk for disease progression. The
      mutational status of the immunoglobulin variable heavy chain genes (VH) is one of
      the major molecular prognostic factors. In this study we evaluated the
      association between the immunoglobulin VH gene mutation status and the clinical
      characteristics and outcome in 65 CLL patients that had been followed for a
      considerably long period at our institution. At diagnosis, patients with
      unmutated VH genes had higher median lymphocyte counts (P=0.001), higher total
      tumor mass score (P=0.001) and more often presented at an advance clinical stage
      (P=0.005) compared to patients utilizing mutated VH genes. Moreover, the median
      survival of patients with unmutated VH genes was considerably shorter (VH
      unmutated, 56 months, VH mutated, 125 months; P<0.001). These data confirmed the
      prognostic value of immunoglobulin VH genes mutational status in CLL, which
      divides the disease in two prognostic subsets in terms of overall survival and
      clinical characteristics of the disease. Analysis of the mutational status of the
      immunoglobulin VH genes may allow for an individualized approach to CLL treatment
      in the near future.

PMID- 17211298
TI  - Correlation of diabetic maculopathy and level of diabetic retinopathy.
AB  - One of the retinal changes during diabetic disease is appearance of diabetic
      maculopathy, which main characteristic is development of edema in the area of
      m.lutea. It is the main cause of decrease in vision and is found in about 10% of
      diabetic patients. The aim of this paper is to determine the frequency of
      diabetic maculopathy, prevalence of the found type of maculopathy and correlation
      with retinopathy level. MATERIAL AND METHODS: the study comprised consecutive
      type 2 diabetic patients referred to the Unit for Laser Photocoagulation of the
      Clinic for Eye Diseases by ophthalmologists from other health centers. A total
      number of 86 patients were recruited in the study. Both ophthalmoscopic and
      biomicroscopic examinations of eye fundus as well as fluorescein angiography were
      performed. Grading of severity and level of both maculopathy and retinopathy has
      been done according to International Classification. RESULTS: A high presence of
      maculopathy in the examined patients (89.5%) was found as a result of previous
      high selection of diabetic patients by their ophthalmologists. The high selection
      has also an impact on correlation of diabetic maculopathy onset and disease
      duration, where parallelism with its appearance was registered, but this could
      also suggest that retinal microvascular changes appear very early, prior to
      clinical manifestation of diabetes. Diabetic maculopathy was most frequently
      found in preproliferative and proliferative diabetic retinopathy (93.6% and
      95.3%). Severe forms of diabetic maculopathy with huge edema, numerous hard
      exudates and significant zones of capillary "drop out" of foveal capillary net
      are also associated with preproliferative and proliferative diabetic retinopathy.
      The most frequent type of diabetic maculopahty was the mixed one, where in
      addition to exudative characteristics, elements of ischemia and diffuse leakage
      were also found in 56% of the cases. CONCLUSION: Diabetic maculopathy is only one
      of the manifestations of diabetic disease and it is the main cause of visual
      acuity impairment in diabetic patients. It is a reflection of already existing
      more significant and advanced biochemical and pathophysiological processes on the
      level of retinal microcirculation. The mixed type of diabetic maculopathy was
      predominant and its onset and severity was in correlation with concurrent
      diabetic retinopathy. Prevention of retinal changes and sight preservation in
      these patients, in addition to timely and adequate ophthalmologic treatment,
      induces multidisciplinary approach since the principal cause of microvascular
      complications is hyperglycemia in correlation with many risk factors, such as
      hypertension and dyslipidemia.

PMID- 17211299
TI  - Comparative analysis between transcranial color duplex sonography and magnetic
      resonance angiography in patients with stroke.
AB  - BACKGROUND: Cerebrovascular diseases are among the most frequent diseases of the
      central nervous system. There are several diagnostic methods for cerebral blood
      vessels evaluation. The optimal test is characterized with low risk, availability
      and diagnostic certainty. Lately, the rapid development of transcranial color
      duplex sonography (TCCS) and magnetic resonance angiography (MRA) have shown that
      they are the most useful techniques for non-invasive investigation of cerebral
      blood vessels. PURPOSE: To compare transcranial color duplex sonography (TCCS)
      and magnetic resonance angiography (MRA) in the evaluation of patients with
      stroke. METHODS: Using TCCS, hemodynamic parameters were measured in intracranial
      arteries in 50 patients with ischemic stroke. Magnetic resonance angiography
      (MRA) was carried out in all patients during 1-5 days after sonography. According
      to TCCS findings, patients were divided into the following groups: I) group with
      normal findings; II) group with occlusion of middle cerebral artery (MCA)
      branches; III) group with MCA stenosis and IV) group with occlusion of MCA trunk.
      TCCS findings were compared with MRA findings, which were considered as a golden
      standard. Sensitivity, specificity, positive predictive value, negative
      predictive value and the overall accuracy of the test were determined. RESULTS:
      In all groups of patients, high levels of sensitivity, specificity, positive and
      negative predictive value were obtained. The certainty of TCCS in determining
      normal and pathologic findings of the intracranial arteries was at risk level
      less than 1%. CONCLUSION: TCCS is a safe and secure diagnostic modality which
      serves for fast and recurrent evaluation of intracranial vessels patency in the
      acute stroke phase and it is an imaging method with high sensitivity and
      specificity in determining the steno-occlusive intracranial lesions.

PMID- 17211301
TI  - Hyperfractionation as an altered fractionation regimen in primary radiotherapy
      for squamous cell carcinoma of the larynx.
AB  - The aim of the study was to investigate the efficacy of hyperfractionation as an
      altered fractionation treatment schedule in comparison with conventional
      fractionation in primary definitive radiotherapy for laryngeal squamous cell
      carcinoma. From March 1999 to December 2000, a group of 28 patients with
      previously untreated squamous cell carcinoma of the larynx were irradiated with
      conventional fractionation to total doses of 66 to 70 Gy in 33 to 35
      fractions/6.5 to 7 weeks, 2 Gy/fraction/day, 5 days/week. From January 2001 to
      June 2004, the other 27 patients with the same diagnosis, were treated
      prospectively with hyperfractionation receiving radiotherapy delivered at 1.2
      Gy/fraction, twice daily, 5 days/week to 74.4 to 79.2 Gy/62 to 66 fractions/6.2
      to 7 weeks. Complete response rates after two months of radiotherapy completion
      were 78.6% (22 of 28) and 66.7% (18 of 27) in the conventional fractionation and
      hyperfractionation group, respectively (Fisher exact test; P=0.246). The two year
      loco-regional control rates were 61.0% +/- 18.1 (95% CI) in the conventional
      fractionation group and 45.0% +/- 18.8 (95% CI) in the hyperfractionation group
      (log-rank test; P=0.075). Overall survival rate at two years was 71.0% +/- 16.8
      (95% CI) for the conventional fractionation group and 43.0% +/- 18.7 (95% CI) for
      the hyperfractionation group (log-rank test; P=0.071). The absence of
      statistically significant differences either in loco-regional control or overall
      survival observed between the two treatment modalities suggested that
      hyperfractionation regimen was not more efficacious than conventionally
      fractionated radiotherapy for previously untreated carcinoma of the larynx.

PMID- 17211300
TI  - The impact of functional endoscopic sinus surgery on symptoms in chronic
      rhinosinusitis.
AB  - Chronic rhinosinusitis restricts the quality of life of millions of involved
      patients. The aim of the study was to evaluate how functional endoscopic sinus
      surgery (FESS) modifies symptom profiles in patients with chronic rhinosinusitis.
      Questionnaires were given to eighty patients with chronic rhinosinusitis, who
      underwent FESS, to assess typically related symptoms preoperatively and
      postoperatively. Statistical analyses were performed with the Wilcoxon test.
      Leading symptoms of chronic rhinosinusitis were nasal obstruction in 93.7% and
      post nasal discharge in 86.2% of the patients. Furthermore, patients reported
      anterior nasal discharge in 72.5%, headache in 65% and hyposmia in 62.5% of the
      patients. One year postoperatively all the symptoms were significantly improved :
      nasal obstruction in 87%, post nasal discharge in 74.3%, anterior nasal discharge
      in 70.5%, headache in 59.4% and hyposmia in 58.7% of the patients. Our results
      showed that FESS is an adequate and effective method in treatment patients with
      chronic rhinosinusitis. On the other hand, the questionnaire used in the present
      study was easy to handle for the patients and allowed successful quantification
      of sinusitis-related symptoms.

PMID- 17211302
TI  - External fixation in patients with age over 65 years with distal radius fracture.
AB  - AIM: This study evaluates the final outcome of the treatment of the distal radius
      fractures with external fixation in patients older than 65 years. PATIENTS AND
      METHODS: Thirteen patients over the age of 65 years with a distal radius fracture
      were treated with external fixation. The fracture type was determined according
      the Frykman classification. For evaluation of the outcome six months after the
      operation were used: Stewart Score System; Gartland and Werley; and PRWE (Patient
      rated wrist evaluation). RESULTS: According to the Stewart score system one
      patient has excellent; nine good; and tree have fair result. Gartland and Werley
      score showed that four patients have excellent; six good; and three have fair
      result. According to the PRWE two patients have no pain and no functional
      disability; five have minimal; five have mild pain and functional disability; and
      one has moderate degree and frequency of pain and moderate functional disability.
      Statistically there is strong correlation between Gartland and Werley score and
      PRWE score (r=0.657) and weak correlation between Stewart score and PRWE score
      (r=0.431). CONCLUSION: The external fixation of the distal radius fractures in
      the patients with advanced age enables high degree of functioning of the injured
      wrist and high level of daily activity. Judging from the benefit of enabling an
      "independence" of these persons, the risk for the operative treatment is
      sustained.

PMID- 17211303
TI  - Right heart haemodynamics after lung resection; the role of the transthoracic
      echo-doppler cardiography.
AB  - We analyzed 80 patients with lung resections due to lung carcinoma operated at
      the Clinic for Thoracic Surgery. We performed lobectomy or bilobectomy in all
      cases, the patients were between 50 and 70 years old and the preoperative
      preparing was the same. The patients were divided in 2 groups; group A -- the
      patients with anamnesis for myocardial infarction, arrhythmia, pulmonary
      hypertension or restrictive respiratory disease and group B -- patients without
      such a history. Echo Doppler cardiography was performed in all cases to measure
      the main parameters that present the heart-lung hamodynamics. We found some
      changes even in group B (increased RVEDV, decreased EF, increased pulmonary
      systolic pressure) which can be a reason for cardiac complications after this
      type of surgery. The echo-Doppler cardiography is a sensitive and non-invasive
      method to obtain all valid parameters to present heart-lung haemodynamics.

PMID- 17211304
TI  - Dimensions and muscular architecture of the triangle of Koch.
AB  - The variability in the arrangement of the superficial atrial muscle fibers in the
      areas of the triangle of Koch may be one of the factors influencing the route for
      impulses entering the AV node. The purpose of this study was to present the
      dimensions of the triangle of Koch and to describe the arrangement of the
      subendocardial atrial muscle fibers that form the approaches to the AV node, in
      and around the area of the triangle of Koch. The examination was made on 50 human
      hearts got obtained after autopsies of patients older than 18 years, died from no
      cardiac reasons, and fixed in 10% formaldehyde. The dimensions of the triangle of
      Koch were measured using the caliper. For the analyzing of the arrangement of the
      subendocardial muscle fibers, the right atrium was divided into four areas and
      the atrial endocardium was carefully peeled. The mean value of the area of the
      triangle of Koch (P) was 261.65 +/- 52.30 mm2 (min 160.00; max 375.00), the
      length of side a, was 24.14 +/- 14.2.53 mm (min 18; max 29), side b, was 20.12 +/
      2.42 mm (min 15; max 25) and side c, was 25.80 +/- 2.83 mm (min 20; max 31). The
      analyzing of the arrangement of the subendocardial superficial muscle fibers
      showed that 36 of the specimens had approximately precise patterns of fiber
      orientation within the areas of the right atrium. Variations in the fiber
      orientation were observed in 14 specimens. The knowledge of the anatomic
      features, dimensions and the architecture of the subendocardial muscle fibers of
      the triangle of Koch is the essential for both successful investigation and
      interpretation of the electrophysiological basis of heart dysrithmic diseases.

PMID- 17211305
TI  - Spinal anaesthesia for cesarean section with reduced dose of intrathecal
      bupivacaine plus fentanyl.
AB  - BACKGROUND AND OBJECTIVES: The hypotension following spinal anesthesia remains
      common place in cesarean delivery. The combination of reduced dose of local
      anesthetics with intrathecal opioids makes it possible to achieve adequate spinal
      anesthesia with minimum hypotension. We investigate whether this synergistic
      phenomenon could be used to provide less frequent hypotension while incurring
      adequate spinal anesthesia for cesarean section. METHODS: Forty women scheduled
      for cesarean delivery (twenty in each group) were divided into two groups of
      patients who received a spinal injection of either 13.5 mg of standardized
      isobaric 0.5% bupivacaine or 9 mg of isobaric bupivacaine with 20 microgr
      fentanyl added. Each measurement of a systolic blood pressure less than 95 mm Hg
      or a decrease in systolic pressure of greater than 25% from baseline was
      considered as hypotension and treated with a bolus of 5 to 10 mg of intravenous
      ephedrine. The quality of surgical anesthesia was evaluated also. RESULTS: Spinal
      block provided excellent surgical anesthesia in almost all patients. Peak sensory
      level was higher (Th 2-3 vs. Th 4-5) and motor block was more intense in the
      plain bupivacaine group; the patients from standardized bupivacaine group were
      more likely to require treatment for hypotension (75% vs 15%) and had more
      persistent hypotension (4.6 vs. 1.0 hypotensive measurements per patient) than
      patients in the reduced bupivacaine-fentanyl group. Mean ephedrine requirements
      were 22.0 mg and 3.5 mg, respectively. Patients in the bupivacaine group also
      complained of emetic effects more frequently than patients in the reduced dose
      bupivacaine-fentanyl group. CONCLUSIONS: Bupivacaine 9 mg plus fentanyl 20
      microgr provided spinal anesthesia for cesarean delivery with less hypotension
      and vasopressor requirements while ensuring excellent perioperative surgical
      anesthesia.

PMID- 17211307
TI  - [Techniques and applications of noninvasive high-resolution ultrasound imaging].
AB  - Today manufacturers propose echographic systems with a resolution ranging from
      100 microm down to 30 microm. This requires ultrasonic frequencies ranging from
      20 to 60 MHz. However, when associated with an increase in the attenuation of the
      wave in the media this limits the applications to superficial exploration. High
      frequencies also bring special technological limitations mainly in the fields of
      transducers, electronics, and acoustic coupling. Although high-resolution
      echography has long remained marginal and been used for the exploration of the
      skin or the anterior chamber of the eye, new powerful and easy-to-use devices
      have recently appeared on the market. With these new products, new applications
      have also appeared such as the exploration of the oral cavity or small laboratory
      animals (mice).

PMID- 17211308
TI  - [High-resolution ultrasound imaging of the mouse].
AB  - Small-animal ultrasound imaging has been made possible using high-resolution
      imaging devices. The spatial resolution is therefore sufficient to accurately
      measure anatomical parameters in mice. This paper reviews some of the main
      applications of high-resolution ultrasound imaging of the mouse and highlights
      what could be the forthcoming advances.

PMID- 17211310
TI  - [Applications of noninvasive high-resolution ultrasound imaging in
      ophthalmology].
AB  - While ultrasonography has been applied to eye examination since the beginning of
      medical applications of ultrasound, the use of high frequencies is relatively
      recent in this context. Recent developments since the 1990s have made devices
      available that are well suited for examining the anterior segment as well as the
      posterior pole, providing precise data for corneal lesions, iris, chamber angle,
      and ciliary body abnormalities, and lesions of the papilla and macula.

PMID- 17211309
TI  - [High-resolution ultrasonography: utility in diagnosis, treatment, and monitoring
      dermatologic diseases].
AB  - Although less precise than histological examination, high-resolution skin imaging
      is a noninvasive technique that provides complementary information to the
      clinical examination: the lesion's US structure as well as its lateral and depth
      extension. Ultrasonography helps in diagnosis and initial management by measuring
      melanoma thickness (so as to remove this lesion with safety margins) before
      destructive treatment (cryosurgery or radiotherapy), by showing tumor limits, or
      by detecting subclinical recurrence during the follow-up. In this paper,
      ultrasound images will be correlated with clinical and histological data in
      various clinical situations such as tumors, edema, cutaneous infiltration,
      sclerous tissues, hyperlaxity, and cutaneous aging.

PMID- 17211311
TI  - [Value of 3D-4D sonography in fetal and gynecological ultrasound examination:
      principles and indications].
AB  - Three-dimensional ultrasound has become an essential tool for visualization of
      fetal structures in the past few years. The recent improvements in transducers
      and signal processing provide new information, particularly in obstetrics and
      gynecology sonography. The present paper will present the most recent advances in
      volume acquisition and presentation modes followed by results of fetal organ
      visualization in normal and abnormal cases as well as applications in gynecology.

PMID- 17211312
TI  - [Three-dimensional echography: cardiovascular applications].
AB  - Real-time three-dimensional echocardiography is currently used in a standard
      echocardiographic examination. Volume-rendered images better identify and locate
      anatomic structures and improve our comprehensive approach to various heart
      diseases. The assessment of mitral valve disease and congenital cardiopathies and
      the measurement of left ventricular mass, volume, and ejection fraction are the
      three main applications of three-dimensional echocardiography. Three-dimensional
      vascular imaging is an emerging and promising application of three-dimensional
      echography. The near future of three-dimensional echography requires the
      integration of all modalities of conventional echography in three dimensional
      probes, a higher image resolution compared to the current situation, as well as
      the development of real-time three-dimensional probes dedicated to
      transesophageal cardiac or vascular examination.

PMID- 17211313
TI  - [Specifications for organized breast cancer screening. Specifications for
      management structures].

PMID- 17211314
TI  - [Specifications for organized breast cancer screening. Specifications for
      radiologists].

PMID- 17211315
TI  - [Familial primary pulmonary hypertension revealed by the association of bilateral
      chemosis, subacute myopia, and exophthalmos].
AB  - PURPOSE: To report a rare case of primary pulmonary hypertension (PPH) revealed
      by a relapsing chemosis, exophthalmos, and subacute myopia. PATIENTS AND METHODS:
      A 46-year-old woman presented with recurrent bouts of chemosis, exophthalmos, and
      subacute myopia. Her visual troubles were triggered by physical effort. She had a
      history of a longstanding high blood pressure that was noncompliant to all
      conventional hypotensive therapy. Automated refraction under cycloplegia showed
      recent myopia. At observation she had a bilateral, moderate chemosis. Hertel
      exophthalmometer measured a symmetric exophthalmos of 23 mm. Intraocular pressure
      was 20 mmHg OD and 24 mmHg OS. Eye fundus was strictly normal. RESULTS:
      Laboratory analysis showed no thyroid or inflammatory disease. HIV serology was
      negative as were antinuclear antibodies. Orbital CT confirmed the axial,
      symmetric exophthalmos. Echocardiogram brought out the diagnosis of PPH. Genetic
      studies by PCR localized the BMPR2 mutation that is characteristic of the
      familial type of PPH. Symptoms decreased under treatment. DISCUSSION: PPH is a
      rare disease caused by thickening of the arteriolar walls in the pulmonary bed,
      which results in a right-heart hypertension with venous stasis. Many authors have
      reported different posterior segment diseases secondary to PPH. However, anterior
      segment manifestations are extremely rare. These may be caused by a ciliary body
      congestion and retrobulbar vasodilatation. CONCLUSION: The association of
      chemosis, exophthalmos, and subacute myopia is unusual in PPH. We recommend
      keeping in mind the PPH as a differential diagnosis in those cases, especially in
      patients who suffer from high blood pressure.

PMID- 17211317
TI  - [Intraorbital wood foreign body: a case study].
AB  - A 12-year-old child had left orbital trauma by wood. He consulted 4 months after
      for orbital cellulitis with cutaneous fistula. The CT scan showed the presence of
      a left orbital wood foreign body extended to the homolateral cavernous sinus and
      intracranial. Extraction of the wood fragment associated with an adapted
      antibiotic treatment led to clinical improvement without visual recovery. A
      situation of orbital trauma and secondary orbital inflammatory syndrome must
      raise the suspicion of a foreign body of the orbit and motivate emergency imaging
      for optimal management of the disorder.

PMID- 17211316
TI  - [Cotton-wool spots as first ocular manifestation of giant cell arteritis].
AB  - INTRODUCTION: Giant cell arteritis is the most common vasculitis in the elderly.
      Visual loss is established as the most dreaded and irreversible complication of
      the disease, which makes giant cell arteritis an ophthalmic emergency. It is
      important to recognize its various ocular manifestations; isolated cotton wool
      spots are one of them. CASE REPORT: We describe a patient with constitutional
      symptoms and mild visual loss who was found to have giant cell arteritis. The
      ophthalmic examination was significant for only isolated cotton-wool spots. A
      delay in arm-to-retina circulation time was demonstrated by fluorescein
      angiography. Prompt treatment with corticosteroids led to preservation of vision
      and uneventful resolution of the cotton-wool spots. DISCUSSION: Common
      ophthalmologic presentations include anterior ischemic optic neuropathy or
      choroidal ischemia when short posterior ciliary arteries are involved, and
      central retinal artery occlusion. Retinal ischemia has also been recognized as a
      possible manifestation. Because the disease concerns medium-size and larger
      arteries, it cannot involve terminal retinal arterioles to produce cotton-wool
      spots. These are probably caused by platelet microembolization from the partially
      thrombosed regional arteries. CONCLUSION: Isolated cotton-wool spots can be an
      early ophthalmoscopic finding in giant cell arteritis and precede severe
      irreversible visual loss. Their detection is essential because it allows the
      ophthalmologist to establish a prompt treatment and preserve vision.

PMID- 17211319
TI  - Evaluation of a new IOL scleral fixation technique without capsular support.
AB  - PURPOSE: The purpose of this study was to compare a new intraocular lens (IOL)
      scleral fixation technique (scleral incision) with the scleral flap surgical
      technique as regards to efficacy, surgical complications, advantages,
      disadvantages, and surgery costs in cases with no capsular support. MATERIAL AND
      METHODS: This was a retrospective study conducted on thirty patients (30 eyes),
      ten of whom were aphakic, eleven had traumatic cataract, seven had post
      phacoemulsification complications, and two had lens luxation. The patients were
      divided into two groups (I - scleral incision technique and II - scleral flap
      technique) of fifteen patients each, during a study period lasting eighteen
      months. The great majority of the procedures were performed under general
      anesthesia and by the same surgeon. Statistical analysis was done using SPSS. The
      numerical variables were compared using the t test and the categorical ones using
      the Fisher exact test. We performed multifactorial analysis to build a model that
      could predict and compare the complications associated with each technique. An
      explicative model was built using logistic regression. RESULTS: We observed a
      threefold higher rate of complications associated with the scleral flap technique
      when compared to the scleral incision technique. This difference was particularly
      relevant as regards the occurrence of free scleral flap and hyphema. No
      statistically significant differences were observed regarding vitreous
      hemorrhage, choroidal hemorrhage, retinal detachment, difficulty in the external
      pulling of the Prolene suture, breaking of the Prolene suture, and anterior
      chamber collapse. We found a significant association between intraoperative
      complications and the technique used (higher number of complications with the
      scleral flap) and also with some systemic diseases (patients with hypertension
      had more intraoperative complications). The number of late complications
      resulting from the scleral flap technique was much higher than those observed
      with the scleral incision technique; however, the number of the cases we studied
      is insufficient to reach statistical significance. CONCLUSION: The duration of
      the procedure using the IOL scleral incision technique is significantly lower
      than using the scleral flap technique. Intraoperative complications were
      significantly associated with the technique used: more frequent with scleral
      flap. Late complications were mainly associated with systemic and previous ocular
      diseases.

PMID- 17211318
TI  - [Prevalence and description of treatment with intraocular pressure-lowering
      topical medications in continental France].
AB  - PURPOSE: The first objective of the present study was to estimate the prevalence
      of patients treated for glaucoma or ocular hypertension (OHT) with an IOP
      (intraocular pressure) -lowering topical medication. Subjects were 40 years old
      and living in continental France. The second objective was to describe the type
      of therapy, compliance, and the quality of life of the subjects treated. METHODS:
      This study was a telephone survey conducted in a general population on a
      representative sample of 5726 subjects in 2004. Subjects treated for glaucoma or
      OHT were defined as those declaring use of eye drops for more than 1 month and
      mentioning one of the 52 registered IOP-lowering topical medications and/or
      stating that they were taking eye drops for glaucoma or OHT. Quality of life was
      measured using the GlauQOL-17 questionnaire. RESULTS: 237 subjects (4.1%)
      corresponded to this definition. The prevalence increased with age, from 0.7% in
      subjects aged 40-44 years to 10.6% in those aged 80 years or more. The age
      standardized prevalence was higher in the Paris area (5.3%), the Mediterranean
      (4.5%), and the Southwest (4.7%), and lower in rural areas (3.2%), and in
      subjects with less than high school education (2.9%). Beta-blockers (49.5%) and
      prostaglandins (37.4%) were the most frequent treatments, followed by carbonic
      anhydrase inhibitors (15.3%), sympathomimetics (5.7%), and myotics (1.3%).
      Compliance was not total in 39% of the patients (22% of those treated with once-a
      day dosage). DISCUSSION: The results of the present study are in line with French
      health authority data and with the results of the French "Glaucoma and
      intraocular high pressure, one day" study results. Moreover, the lower prevalence
      in regions with low medical density, low socioeconomic level, and rural areas,
      suggest that glaucoma or OHT might be underdiagnosed. CONCLUSION: On the basis of
      this first nationwide study, it can be estimated that the prevalence of subjects
      treated with IOP-lowering topical medications is about 1.2 million in France. The
      number of daily doses appears to influence compliance.

PMID- 17211320
TI  - [Clinical evaluation of the dynamic rebound tonometer Icare].
AB  - PURPOSE: The Icare dynamic tonometer (impact or Rebound tonometry) is a new
      tonometer based on making a moving object collide with an eye and on monitoring
      the motion parameters of this object following contact. The purpose of this study
      was to assess intra- and interobserver variability of IOP measurements with the
      Icare and their correlations with Goldmann applanation tonometry (GAT) and
      central corneal thickness (CCT). MATERIAL AND METHODS: A prospective study
      including three groups of patients: group 1 (50 normal subjects), group 2 (50
      patients with OHT or POAG and GAT IOP>22 mmHg), and group 3 (38 glaucomatous
      patients with GAT IOP< or =22 mmHg). In group 1, three consecutive IOP
      measurements were taken by three distinct observers with Icare followed by three
      GAT measurements by the same clinician. In group 2, the same procedure was
      followed from patients 1 to 25 and the reverse sequence from patients 25 to 50
      after a 10-min break. In group 3, only one clinician took three GAT measurements
      followed by three Icare measurements after a 10-min break to exclude a
      tonographic effect in eyes with statistically normal-range IOPs. RESULTS: : In
      group 1, intraobserver variability was about 6% for each observer (NS). There was
      no learning curve effect. The interobserver variation coefficient was 6.4%. Icare
      overestimated IOP compared to GAT (mean difference, 1.5-2.2 mmHg) (p<0.001).
      Icare IOP was 23.4 mmHg for observer 1 when GAT was 22 mmHg (95% individual CI,
      18-28.9 mmHg). In group 2, intraobserver variation coefficients of the IOP ranged
      from 5% to 5.4% (NS). Icare overestimated IOP by mean 0.84 mmHg compared with
      GAT. In group 3, mean IOP was not different between Icare and GAT. Icare IOP of
      20.7 mmHg corresponded to a value of 22 mmHg using GAT. In this group,
      correlations between CCT and IOP measurements were higher for Icare than for GAT
      (p=0.062). CONCLUSION: Icare measures IOP in an unanesthetized sitting patient in
      a very brief time. Patient's minimal cooperation is needed. As long as the device
      is correctly positioned, the learning curve is short. Icare gives reproducible
      IOP measurements. Intra- and interobserver variability of IOP measurements are
      close to those of GAT. Icare overestimates IOP measurements an average 1.5 mmHg
      compared with GAT. Whatever the IOP level, Icare IOP measurements are well
      correlated with GAT. To a greater extent than for GAT, the reliability of IOP
      measurements is influenced by CCT. This tonometer can be used as a screening
      device for ocular hypertension as long as CCT measurements can be taken.

PMID- 17211321
TI  - [Specifications of retinal detachment surgery in highly myopic eyes of 10 or more
      dioptres and hemorrhagic complications: 79 cases].
AB  - INTRODUCTION: We report a series of 79 eyes undergoing primary surgery for
      rhegmatogenous retinal detachment associated with severe myopia greater than 10
      diopters. Specific surgical procedures are recommended for these patients in
      order to minimize the high incidence of postoperative hemorrhagic complications.
      MATERIALS AND METHODS: Seventy-nine eyes of 76 patients treated for retinal
      detachment with severe myopia greater than 10 diopters were reviewed. Scleral
      buckling was performed in 21 eyes and pars plana vitrectomy in 58 eyes. RESULTS:
      After a mean follow-up period of 23.8 months, the final anatomical success rate
      was 93.7% (74 cases). Postoperative hemorrhagic complications (suprachoroidal
      hemorrhage and vitreous hemorrhage) occurred in four cases after scleral buckling
      and in ten cases after vitrectomy. DISCUSSION: In this study, primary scleral
      buckling for retinal detachment was less frequently performed than vitrectomy.
      Broad scleral buckling may not be associated with higher postoperative
      hemorrhagic complications, when the buckle does not extend over six clock hours.
      Postoperative hemorrhagic complications also occurred after vitrectomy; however,
      scleral buckling associated with vitrectomy does not seem to increase the
      complication rate. CONCLUSION: This retrospective study of 79 cases of
      rhegmatogenous retinal detachment with severe myopia higher than 10 diopters
      suggests that vitrectomy is often considered a primary procedure. Broad scleral
      buckling associated with vitrectomy is a safe and effective procedure, with an
      acceptable incidence of complications when not extending over six clock hours.

PMID- 17211324
TI  - [Deep nonpenetrating sclerectomy: technical aspects].
AB  - Classical trabeculectomy is affected by numerous and serious drawbacks that have
      led to the development of nonpenetrating surgery. In this new filtering
      technique, the aqueous outflow through the juxtacanalicular trabeculum and
      Schlemm's canal is selectively increased without penetrating the anterior
      chamber. This is best performed by means of a careful and precise dissection of
      the outflow resistance pathway and by removing its most resistant portion. This
      requires both mastery of the microdissection technique and high-precision
      surgical tools. Finally, sound knowledge of the morphological features of such
      delicate structures is of paramount importance to avoid intra- and postoperative
      complications.

PMID- 17211322
TI  - [Recurrence after primary vitrectomy for pseudophakic retinal detachment].
AB  - INTRODUCTION: The aim of this study was to evaluate the incidence of pseudophakic
      retinal detachment (RD) recurrence after primary vitrectomy. PATIENTS AND
      METHODS: This was a prospective nonrandomized consecutive case series study,
      evaluating two series presenting to our clinic with pseudophakic RD from 1998 to
      2004 (103 eyes of 97 patients). The study included 24 consecutive pseudophakic
      eyes treated with gas vitrectomy surgery with placement of an encircling band
      from January 1998 to December 2000 (group A) and 79 consecutive pseudophakic eyes
      treated with gas vitrectomy surgery with no encircling band from January 2001 to
      December 2004 (group B). Pre- and postoperative characteristics were analyzed in
      both groups. In the cases of postoperative RD recurrence, we particularly
      analyzed the pre- and postoperative risk factors, as well as the anatomic and
      functional outcome. RESULTS: Visual acuity improved in 74/103 (71.8%) eyes from
      both groups postoperatively. Recurrence of RD after primary vitrectomy occurred
      in eight of 103 (7.8%) eyes in both groups. More specifically, two of 24 (8.3%)
      eyes in group A and six of 79 (7.6%) eyes in group B presented a recurrence after
      gas vitrectomy with encircling band and gas vitrectomy alone, respectively. Among
      these eight eyes, four eyes (50%) presented proliferative vitreoretinopathy (PVR)
      at the time of initial vitrectomy, while all eyes presented PVR at the time of
      recurrence (one grade B, seven grade C). These eyes required two additional
      interventions on average. Five eyes (62.5%) required silicone-oil tamponade for a
      good anatomic reapplication. DISCUSSION: These results show that recurrence after
      primary vitrectomy for pseudophakic RD is most often related to the presence of
      PVR before or after the first intervention. This series reports a success rate of
      91.7% and 92.4%, respectively, for group A and B, thus demonstrating the efficacy
      of vitrectomy in the treatment of pseudophakic RD. This study also shows a
      nonsignificant difference in the recurrence rate among patients treated by gas
      vitrectomy and those undergoing gas vitrectomy in association with encircling
      band placement, which raises the question of the usefulness of an additional
      encircling band in pseudophakic RD.

PMID- 17211325
TI  - [How does nonpenetrating surgery work?].
AB  - The aqueous leaves the anterior segment via two different pathways, the classical
      and the uveoscleral routes. The main resistance to aqueous egress lies at the
      level of the juxtacanalicular trabeculum and the inner wall of Schlemm's canal.
      Impaired function of either one of these structures leads to a decrease in the
      outflow facility which eventually results in a significant increase in
      intraocular pressure. Success of non-penetrating surgery lies in the physical
      removal of these resisting elements without compromising of the structural
      integrity of the eye, thus preventing a sudden drop in the intraocular pressure.
      The selective filtration through the trabeculodescemetic membrane, the evacuation
      of the aqueous in the intrascleral space, the subconjunctival bleb and the
      subchoroidal space, and the final drainage into collector channels and drain
      veins are the key elements for a successful deep sclerectomy.

PMID- 17211326
TI  - [Adjuvants to nonpenetrating surgery: drains and implants].
AB  - The nonpenetrating filtering procedure requires a functioning intrascleral space.
      This space is created after a careful dissection and resection of the deep
      scleral flap. In order to prevent a collapse of the remaining superficial flap
      that forms the roof of the intrascleral cavity, a space maintainer is usually
      inserted at this stage of surgery. Two different types of drainage devices are
      used: absorbable and nonabsorbable implants. The first type is currently made of
      porcine collagen material that is slowly absorbed over time, whereas the second
      is usually made of nondegradable materials that permanently remain in the scleral
      bed. No significant differences in the surgical technique can be found between
      the two types of implant. The long-term results are fairly similar for both of
      them, the absorbable implant being slightly more advantageous.

PMID- 17211329
TI  - [Liver transplantation for hepatocellular carcinoma: is there life outside the
      Milan criteria?].

PMID- 17211327
TI  - [Complications of deep nonpenetrating sclerectomy].
AB  - The typical complications related to nonpenetrating surgery are the rupture of
      the trabeculodescemetic membrane; postoperative ocular hypertension, which
      requires a laser goniopuncture; fibrosis of the filtering bleb, which is best
      cured by local antimetabolite application; or the development of a polycystic
      bleb, which is efficiently resolved by needling. While small perforation of the
      trabeculodescemetic membrane can be handled using simple countermeasures, large
      breaks ultimately result in converting the surgery into a penetrating procedure
      akin to trabeculectomy. Other classical complications can arise that comprise
      shallow anterior chamber, positive Seidel, hyphema, severe inflammation,
      choroidal detachment, or prolonged hypotony with associated maculopathy. They can
      occur in other types of filtering surgery as they are not specific to the
      nonpenetrating procedure and they differ only in prevalence.

PMID- 17211330
TI  - [Nosocomial infection by HBV: an underrated risk factor?].

PMID- 17211331
TI  - Long-term survival of patients downstaged by oxaliplatin and 5-fluorouracil
      combination followed by rescue surgery for unresectable colorectal liver
      metastases.
AB  - OBJECTIVES: To evaluate long-term survival of patients resected for primarily
      unresectable colorectal liver metastases downstaged by systemic chemotherapy.
      METHODS: Among a group of 82 patients with advanced colorectal cancer, 39 had
      unresectable liver metastases. After treatment with systemic 3-weekly 5FU/folinic
      acid/oxaliplatin chemotherapy, the outcome of 11 patients made resectable thanks
      to chemotherapy was compared to that of 28 patients who were not. Criteria for
      non-resectability consisted of diffuse bilobar invasion with inability to achieve
      complete resection, unilobar or bilobar invasion plus vascular extension
      (invasion of inferior vena cava or 2 supra-hepatic veins plus continuity with the
      3rd) or involvment of hepatic pedicle. Before and after surgery, CT scan
      evaluation was performed every 2 months. Progression free survival was defined as
      the time between starting chemotherapy and recurrence of the disease. We used
      Kaplan-Meier survival curves and log-rank test for comparisons, P values were two
      sided and considered significant if<0.05. RESULTS: Progression free survival
      times were 14 and 6 months, median overall survival were 60 and 18.5 months,
      respectively, in favour of secondary resected subjects. CONCLUSION: Considering
      the magnitude of the survival benefit, one may question the need and feasibility
      for trials to assess more formally the impact of surgery in that setting.

PMID- 17211332
TI  - [Epigenetic changes and liver carcinogenesis].
AB  - The molecular mechanisms involved in liver carcinogenesis are poorly understood.
      Over the past decade, epigenetic changes (DNA methylation) have received
      increasing attention for their potential involvement in the development of
      hepatocarcinoma. The DNA methylation level is influenced by environmental factors
      (folate and methionine diet), as well as by genetic factors
      (methylenetetrahydrofolate reductase/MTHFR polymorphisms). These findings provide
      new insight into the understanding of liver carcinogenesis. Interventional
      studies are now required to determine the role of folate supplementation in the
      development of liver tumors in targeted patients.

PMID- 17211333
TI  - [Recommendations for the management of Helicobacter pylori infection according to
      Maastricht 3 guidelines].

PMID- 17211334
TI  - Initial endoscopic description of esophageal squamous cell carcinomas.
AB  - INTRODUCTION: The aim of this study was to evaluate initial endoscopic practices
      at diagnosis of esophageal squamous cell carcinoma in comparison with current
      recommendations. We wanted to develop a standard model for the endoscopy report
      which could be used in routine practice. PATIENTS AND METHODS: From January 2000
      to December 2002, 122 patients were hospitalized for esophageal squamous cell
      carcinoma. The initial endoscopic reports were reviewed retrospectively and
      compared with a model report established on the basis of current recommendations.
      RESULTS: One hundred and nineteen reports were re-examined. The principal reason
      for performing the endoscopic examination was dysphagia in 73.9% of patients.
      Tumor measurements (height, upper and lower extremities) were recorded in 51.2%,
      79% and 41% of reports, respectively. 14.4% of the analyzed reports concerned
      endoscopic procedures which were performed after a first endoscopic examination
      because the initial report provided an imprecise tumor description. Tissue
      samples taken during the initial endoscopy allowed a pathological diagnosis in
      94.2% of patients. Lugol staining was performed in 2.5% of procedures.
      CONCLUSION: Insufficiently rigorous reporting compromises the reliability of
      initial upper digestive endoscopic procedures. Application of a standardized
      model for routine practice would favor more complete reports, starting with the
      first procedure.

PMID- 17211335
TI  - Ano-rectal complaints in general practitioner visits: consumer point of view.
AB  - AIMS: The perception patients consulting for primary care have of anorectal
      disorders has never been evaluated. Our aim was to analyze proctological
      complaints among outpatients consulting general practitioners. PATIENTS AND
      METHODS: Among 1484 physicians who responded to a nationwide mailing in France,
      161 enrolled 437 females and 358 males consulting between October 2004 and
      December 2005. RESULTS: Females were younger than males (46 +/- 15 vs 51 +/- 13
      years) (p<0.0001). Intermediate and upper social-occupational categories were
      overrepresented as compared with the general population. Symptoms were pain
      (48%), bleeding (37%), swelling (26%) and pruritus (24%). For 76%, these symptoms
      persisted for less than one month and 58% mentioned earlier visits or prior
      treatment. The first manifestation was correlated with a pregnancy in 31% of
      women. Present symptoms were secondary to acute constipation (52%), stress (33%),
      ingestion of spices (29%) or alcohol (20%), and diarrhea (8%). Symptoms were
      considered important in 61% or a cause of anxiety in 33% of patients. Treatment
      was prescribed for all patients: ointments (90%), phlebotonics (66%) or
      suppositories (51%), in combination for 75% of prescriptions. Patients preferred
      oral medicines (41%), ointments (30%) and suppositories (7%). CONCLUSION:
      Proctological complaints are a reason for repeated visits to the general
      practitioner and lead to repeated prescriptions. Patients appreciate anti
      hemorrhoidal treatments variably.

PMID- 17211336
TI  - [The role of neoadjuvant chemoradiation in pancreatic cancer].
AB  - Although complete surgical resection, when possible, leads to prolonged survival
      in pancreatic cancer, if used alone, its results remain sub-optimal. Neoadjuvant
      strategies are recent in pancreatic cancer: in primary resectable tumors, they
      ensure that all patients obtain additional treatment to complete surgery; in
      locally advanced tumors, they allow a better selection of candidates for curative
      resection. By delaying surgery, neoadjuvant strategies modify the initial
      diagnostic process and the symptomatic treatment of pancreatic cancer. Several
      recent phase I-II studies have confirmed the feasibility and efficacy of the
      association of chemotherapy and radiotherapy, which is well-tolerated and is
      associated with better local control and survival. Due to the aggressiveness of
      pancreatic cancers, most recent cytotoxic agents should be associated with modern
      radiation techniques. Neoadjuvant chemoradiation is under evaluation in
      pancreatic cancers, and no randomized phase III trials comparing neoadjuvant and
      adjuvant therapeutic sequences has been reported. Moreover, radiological and
      pathological evaluations, not only at diagnosis, but also after preoperative
      chemoradiation, must be standardized to improve the selection of patients who
      will benefit from this multi-modal treatment.

PMID- 17211338
TI  - [Current trend: small bowel ischemia].

PMID- 17211339
TI  - [Clinical case: a mesenteric vein thrombosis].

PMID- 17211341
TI  - [Questions to Professor Eric Lerebours].

PMID- 17211343
TI  - [Jaundice after induced ovulation by human recombinant follicle stimulating
      hormone (Gonal-f].

PMID- 17211344
TI  - [Severe varicella infection during treatment with infliximab for Crohn's
      disease].
AB  - Immunosupressive agents have improved the treatment of severe Crohn's disease.
      Infliximab is increasingly used in the treatment of Crohn's disease refractory to
      the usual treatment or with fistulas. However, there is a risk of infection and
      benign viral infections can became severe. We report the case of a patient
      treated by azathioprine and infliximab who developed serious chickenpox with
      multi visceral localisations and transfer to intensive care. There are a few
      cases of severe varicella infection in the literature with hepatitis and
      pneumonia in patients treated with infliximab. We review the clinical aspects,
      therapeutic strategy and prevention of chickenpox in immunodepressed patients.

PMID- 17211345
TI  - Ileosigmoid knotting in a child. The first case report in a French girl.
AB  - Ileosigmoid knotting occurs when the ileum wraps around the base of an elongated
      sigmoid colon. It is rare in developed countries, especially in children. The
      authors report the first case of ileosigmoid knotting in a Caucasian French girl.

PMID- 17211346
TI  - [Reactivation of hepatitis B after cessation of Rituximab monotherapy].

PMID- 17211347
TI  - Primary hepatitis C virus infection in an intravenous drug user: kinetics of
      virological markers.

PMID- 17211348
TI  - Lymphocytic meningitis with infliximab for ulcerative colitis.

PMID- 17211349
TI  - [Does hepatogastroenterology lead to Rome?].

PMID- 17211350
TI  - Diagnostic value and learning curve of transbronchial needle aspiration in
      thoracic surgery.
AB  - AIM: Transbronchial needle aspiration (TBNA) is particularly indicated in
      diagnosing mediastinal masses or lymphoadenopathy proximal to the airways.
      Nowadays TBNA has not been widely accepted among pulmonologist and thoracic
      surgeons. Since its correct management could reduce patient morbidity we adopted
      this method. Here is presented an overview of our experience over a 18-months
      training period. METHODS: Fifty patients underwent TBNA. They presented non
      diagnosed paratracheal or peribronchial lymphadenopathy or masses of >1 cm. TBNA
      has been considered in order to spare patients the need for more invasive
      diagnostic procedures. TBNA has been performed with flexible bronchoscope and 19
      gauge or 21-gauge needle. RESULTS: We made diagnosis of disease in 25 of 41
      patients whose adequate sampling was obtained. 16 cases showed absence of disease
      despite criteria for adequacy have been confirmed, 9 cases presented an
      inadequate specimen. The overall diagnostic yield and sensitivity were 50% and
      86%. The overall accuracy was 76%. Considering the last 6 months of the training
      period diagnostic yield increased from 18.7% to 88.2% (P<0.001),accuracy from
      56.2% to 88.2% (P=0.04) and frequency of inadequacy decreased from 43.7% to 11.7%
      (P=0.046). CONCLUSIONS: TBNA resulted a successful diagnostic tool in selected
      cases as it is safe and permits to spare patients the need for more invasive
      procedures. These data revealed that experience is mandatory in order to achieve
      acceptable RESULTS: We think that an experienced operator should require a
      training period of approximately 50 procedures to obtain a good technique
      proficiency.

PMID- 17211352
TI  - [Thoracic sympathetic block by clamping in the treatment of primary
      hyperhidrosis: indications and results in 281 patients].
AB  - AIM: Hyperhidrosis is a disabling troublesome characterized by excessive
      perspiration that produces a significant social and professional deficit for
      patients. It main involves the palmar sides of hands and feet, axillae, face and,
      with a lesser incidence, trunk and scalp. Thoracoscopic sympathectomy represents
      the best approach for this disorder. The aim of our prospective study is to
      assess the outcome, the safety and efficacy after thoracoscopic sympathetic block
      by clipping in the treatment of primary hyperhidrosis. METHODS: Between september
      2002 and april 2005, 281 patients (117 female and 164 male, with a mean age of 28
      years) underwent Endoscopic Thoracic Sympathectomy (ETS) to treat hyperhidrosis
      with palmar, axillar, facial and widespread localization. RESULTS: There were no
      deaths or major intra-operative problems. There was no conversion to open
      surgery. During intermediate and long-term follow up we obtained excellent
      results and few complications. In 3 patients (1.06%) we noted a major
      complication (Horner's Syndrome), but one patient only had the surgical operation
      reversed; compensatory sweating occurred in 61 individuals (21.7%). Gustatory
      sweating occurred in no patient. CONCLUSIONS: The clipping of the thoracic
      sympathetic chain is a reversible surgical technique considered safe and
      effective. Despite of an incidence of complications and/or compensatory sweating
      and according to our operatory results, we conclude that the sympathetic block by
      clamping is the elective treatment for hyperhidrosis.

PMID- 17211351
TI  - Lung cancer after treatment for non-Hodgkin lymphoma.
AB  - AIM: Because of the improvement in treatment and survival of patients with
      lymphoma, late sequelae, including secondary cancers have been extensively
      studied. Lung cancer is one of the two most common solid tumors after Hodgkin's
      disease but fewer studies have been published about lung cancer after non-Hodgkin
      lymphoma (NHL). METHODS: Over the last five years at our Institution we have
      observed 16 patients, 13 male and 3 female, with a mean age of 61 years,
      previously treated for NHL and lung cancer. Median latency between NHL and lung
      cancer was 7 years. In 6 patients (37.5%) the latency period was shorter than 5
      years and 3 of them developed lung cancer within 2 years after the end of NHL
      therapy. RESULTS: Ten patients underwent lung complete resection. Two, 3 and 5
      year survival rate was respectively 52.7%, 26.3% and 13%. In contrast, the median
      survival of non surgical patients was 9 months. Comparison of survival between
      surgical and non-surgical group demonstrated a statistically significant better
      survival for surgically treated patients (P<0.04). CONCLUSIONS: Surgery can
      improve survival in patients with history of NHL and lung cancer. Early diagnosis
      and treatment is crucial. NHL survivors should undergo careful follow-up and
      surveillance for secondary malignancy.

PMID- 17211353
TI  - Kinetics of plasma heat shock protein HSP-70 release in coronary artery surgery:
      on-pump versus off-pump.
AB  - AIM: Heat shock protein HSP-70 is known as protective chaperone molecule
      synthetized in response following ischemia and stress agents. It is detected in
      the myocardium and endothelium as well as in the circulation. Damaged as well as
      viable but exposed to stress cells contribute to the release of HSP-70 into the
      circulation. The aim of the study was to investigate if cardiopulmonary bypss
      (CPB) leads to more circulating HSP-70, on the basis of comparison dynamics of
      plasma concentration HSP-70 in 8 men undergoing procedures with the use of CPB
      (coronary artery bypass grafting, CABG group) and 8 men undergoing off-pump
      surgery (OPCAB group). METHODS: Blood samples were taken preoperatively, twice
      intraoperatively, immediately after surgical procedure (1 h) and 24-hours
      thereafter. The concentration of plasma HSP-70 was measured by means of
      immunoassay. The derived results were compared statistically with the frequency
      of incidence postoperative atrial fibrillation (AF). RESULTS: In CABG group was
      observed continuous gradual increase of plasma HSP-70 concentration during the
      operation with the peak 1 h after surgery (P<0.01), in striking contrast to OPCAB
      group, in which was detected small, but non statistically significant increase of
      HSP-70 1 h after operation. Significantly more of circulating HSP-70 it was
      detected in CABG group during the operation and 1 h after surgery (CABG vs OPCAB,
      respectively P<0.015 and P<0.028). In both groups among patients witch AF it was
      found higher postoperative values of circulating HSP-70 compared with the non-AF
      group (P=0.0415). CONCLUSIONS: The use of CPB leads to significant more release
      of HSP-70 into the circulation. According to our findings high plasma
      concentration of HSP-70 may be the measure of operative cellular stress, ischemia
      or injury and may be related with greater onset of postoperative AF. High
      circulating HSP-70 levels is connected with higher incidence of postoperative AF
      after open heart surgery.

PMID- 17211354
TI  - Cinedefecographic findings in patients with obstructed defecation sindrome. A
      study in 420 cases.
AB  - AIM: Obstructed defecation syndrome (ODS) represents a very common clinical
      problem. The aim of this study was to analyze the cinedefecographic findings in a
      group of patients with ODS. METHODS: All patients with ODS were prospectively
      introduced into a database and underwent cinedefecography (CD). The grade of the
      syndrome was assessed by a new ODS score. The validated Agachan-Wexner
      Constipation Score System was also used. Four lateral films were taken during
      resting, squeeze, pushing and postevacuation phases and puborectalis length
      (PRL), anorectal angle (ARA) and perineal descent were recorded and analysed. The
      presence of an increased fixed perineal descent (FPD) and dynamic perineal
      descent (DPD), mucosal rectal prolapse (MRP), recto-rectal intussusception (RRI),
      recto-anal intussusception (RAI), rectocele (RE), enterocele (ET) and
      sigmoidocele (SG) were also evaluated. RESULTS: Between February 2002 and March
      2005, 420 patients, 404 (96.1%) females and 16 (3.8%) males with a mean age of
      49+/-7.7 (range, 21-77) years, underwent CD. In 362 (86.2%) patients CD showed a
      combination of different cinedefecographic findings. RE, FPD and DPD in
      association with RAI or RRI were contemporary observed in 118 (26%) patients.
      MRP, RRI, FPD, RAI and RE were observed as singular finding in 21 (5%), 19
      (4.5%), 12 (2.8%), 3 (0.7%) and 3 (0.7%) patients, respectively. In 6 (1.4%)
      patients a paradoxical contraction of the puborectalis muscle was observed.
      CONCLUSIONS: CD shows that ODS is largely caused by multiple patterns of
      different abnormalities of the rectum and pelvic floor. Any treatment in
      symptomatic patients could be designed to treat multiple combinations of
      different abnormalities.

PMID- 17211355
TI  - Use of the ALN permanent/removable vena cava filter. A multi-centre experience.
AB  - AIM: Vena cava filters are used for the prevention of pulmonary embolism in cases
      of contraindication, failure or complications of the anticoagulant therapy. There
      are no certain data in the literature concerning the effectiveness of vena cava
      filters and, above all, the possible long-term complications are not known. For
      this reason increasing attention is paid to permanent/removable filters that
      permit exploitation of the short-term advantages of vena cava interruption,
      eliminating the possible long-term complications. We have reported the results of
      a multicentre experience concerning ALN permanent/removable vena cava filters in
      a total of 276 patients. METHODS: Vena cava filters were placed in 276 patients
      via the jugular, femoral and brachial vein. The filter was removed in 43 patients
      after 3 months and in 28 patients after 6 months. RESULTS: In 1 case, due to
      incomplete opening of the filter, immediate percutaneous removal was performed
      and another filter was positioned. In 5 cases it was not possible to remove the
      filter, in 1 case due to inexperience and in the remaining cases due to adhesion
      of the head or claws of the filter to the wall of the vein. No problems occurred
      in the other cases. CONCLUSIONS: The ALN vena cava filter is safe, easy to
      position and remove even a long time after placement. Currently permanent filters
      should be used only for patients with poor survival expectancy whereas in all
      other cases the use of removable filters is preferable.

PMID- 17211356
TI  - Return to home early days after acute aortic dissection surgery.
AB  - AIM: The length of hospital stay after acute aortic dissection surgery tends to
      be prolonged. The aim of this study is to assess the feasibility of our protocol
      for early discharge after acute aortic dissection surgery. METHODS: This study
      enrolled 17 consecutive acute aortic dissection patients who returned to their
      own home within 2 weeks of surgery. In seven patients total aortic arch
      replacement was performed and in 7 partial arch replacement. The main aim of the
      first 24 h after surgery was to achieve early extubation. Patients were
      encouraged to return to their own home 4 days and later after surgery. The
      prerequisite criteria for discharge were the following: independent mobility,
      stable hemodynamics, apyrexia, adequate oral intake, normal bowel function,
      healthy surgical wound and the patient's agreement for discharge. RESULTS: The
      mean age of these patients was 59. The postoperative ventilation time, length of
      intensive care unit stay and postoperative hospital stay were 11 h, 37 h and 6.9
      days, respectively. Two (12%), 13 (76%) and 14 (82%) patients returned to their
      own home by postoperative day 4, 7 and 10, respectively. Three patients were
      readmitted to a peripheral hospital in the 4 week postoperative period. The
      reason for all readmissions was lack of family support. Two other patients
      underwent pericardiocentesis for pericardial effusion at an other hospital as
      outpatients. There was no complication caused by early discharge. CONCLUSIONS:
      Early discharge after aortic dissection surgery is safe and recommended to
      patients who have normal bowel function and adequate family support.

PMID- 17211357
TI  - [A gastric polypoid signet ring cell carcinoma].
AB  - AIM: The authors signal a case of gastric polypoid signet ring cell carcinoma, of
      particular interest for its rarity like show from the review of the literature,
      which is the first to have been described after Tabaru's citation. METHODS: The
      study has been carried out at the Department of Surgical and Oncological Sciences
      of the University of Palermo. It has been based on 2000 cases analysed from June
      2001 to December 2003. RESULTS: The authors advance some and emphasizes the
      diagnostic flow chart and therapeutic choices adopted. CONCLUSIONS: We agree that
      the endoscopic polypectomy is surgical procedure of first approach, but modifying
      the therapeutic guideline in relation to histologic examination, like happened in
      the case in issue.

PMID- 17211358
TI  - Pulmonary and parotid hydatid cyst: an unusual double localization.
AB  - We described a rare case of pulmonary and parotid cyst for echinococcus
      granulosus in an eighty-one-year-old patient. Lesion was discovered in the lung
      owing to a clinical presentation. A swelling was the only sign in the parotid
      gland. Time between lung and parotid excision was 14 days. Time of
      hospitalizations was 4+/-1 day.

PMID- 17211359
TI  - [Myasthenia gravis and intestinal resection: is dehiscence likely to occur?].
AB  - Experimental and clinical data have proved that anticholinesterase drugs are
      responsible for vigorous peristaltic contractions and for an increase of the
      intraluminal pressure, because they determine muscarinic effects on the smooth
      muscle of the intestine both in small and large intestine. Therefore, a greater
      incidence of intestinal anastomotic disruption has been supposed when
      anticholinesterases are used both in the early postoperative period, to reverse
      curarization, and in myasthenic patients. The authors report a case of a patient
      with myasthenia gravis who received maximal doses of pyridostigmine and underwent
      left hemicolectomy and small intestine resection and afterwards total colectomy
      in order to treat a sigmoid perforated diverticulitis. In the postoperative
      course an anastomotic leak developed after both surgical operations. The authors
      believe that pyridostigmine could have had an important role in the pathogenesis
      of the leak and assert that, when an intestinal resection has to be performed in
      a myasthenic patient, it could be useful to reduce in the preoperative period the
      administration of anticholinesterase drugs and always perform a protective
      ileostomy.

PMID- 17211360
TI  - [Submucosal jejunal lymphangioma: an unusual case with obscure gastrointestinal
      bleeding in an adult, detected by video-capsule endoscopy and treated by
      laparoscopy].
AB  - A 54 year-old man, without any remarkable medical history, was examined for
      recurrent episodes of colicky abdominal pain, over a period of nine months, with
      positive faecal occult blood test. Three months earlier he had undergone an
      extensive evaluation for a single episode of melaena, including upper
      gastrointestinal endoscopy, colonoscopy to the caecum, enteroscopy and an
      abdominal ultrasound scan, that were negative. He was then submitted to the video
      capsule endoscopy (Given Imaging Ltd, Yoqneam, Israel) that revealed a polypoid
      white-yellowish lesion in the mid portion of the jejunum. The patient was
      admitted to our Department of Surgery in January 2005. During the operation,
      performed by laparoscopic video-assisted approach, the lesion, measuring 1.5x2
      cm, was found at about 100 cm from the ligament of Treitz and was successfully
      excised. At histology, the final diagnosis was submucosal lymphangioma. The
      lymphangioma is a benign neoplastic lesion of the lymphatic system that usually
      is present in infancy and is found, in the majority of the patients, in the
      subcutaneous tissue outside the abdomen. The intrabdominal site accounts for less
      than 1% of the cases, and often occurs in the mesentery of the small bowel.
      Finding the lesion in the submucosa of the jejunum in an adult is very rare. The
      case here reported seems unusual to the Authors and worthy of publication because
      of the chronic, ambiguous clinical symptomatology, the occult digestive blood
      loss, and all the diagnostic examinations resulting negative, except for the
      video-capsule endoscopy. Moreover, the choice of the laparoscopic video-assisted
      technique, confirming the expected site of the lesion, with a ''minimal'' small
      bowel resection, made the postoperative course of the patient very short and
      uneventful. He is well and free of disease one year after the intervention. From
      a brief review of surgical literature, the case reported is the second one
      detected by the video capsule endoscopy and the fifth operated on by laparoscopy.

PMID- 17211361
TI  - Retrograde aorto-mesenteric by-pass grafting as treatment option of recurrent
      chronic mesenteric ischemia after thrombosed superior mesenteric artery stenting.
      Report of a case.
AB  - We report a case of early stent failure in a patient with chronic mesenteric
      ischemia and its treatment with a retrograde aorto-mesenteric by-pass. The
      patient was initially treated with angioplasty and stenting. Seven months after
      the procedure complete thrombosis of the stent was achieved. A retrograde aorto
      mesenteric by-pass was performed. After two years the patient remains
      asymptomatic and color Duplex scan confirm the patency of the graft.

PMID- 17211362
TI  - Giant GIST of the mesocolon: report of a case.
AB  - Gastrointestinal stromal tumors are rare neoplasms arising from mesenchymal cells
      of the gastrointestinal tract, that strongly express a class III receptor
      tyrosine kinase, called KIT, due to some mutations in the KIT proto-oncogene. Two
      thirds of GISTs are found in the stomach, 20% to 50% in the small bowel (one
      third in the duodenum), and 5% to 15% in colon and rectum; GISTs, however, may
      rarely be found also in the oesophagus, omentum, mesentery or the
      retroperitoneum. Their treatment is strictly surgical, and only R0 resection can
      achieve good RESULTS: Treatment with Imatinib seems to be promising in case of
      unresectable or metastatic GIST, even if some trials are studying its effects
      after curative resection. GIST of the mesocolon are rare, and as in the other
      locations, require extensive surgery. The Autohrs report a case of giant
      malignant GIST arising from transverse mesocolon, treated by en-bloc resection of
      the tumor with a segment of transverse colon and great omentum.

PMID- 17211363
TI  - [Prototype of a system for electric conduction at contact with laparoscopic
      tools].
AB  - The authors present their prototype of a system for electric conduction at
      contact with laparoscopic tools, devised, designed and produced by them at the
      Politecnico di Torino, Department of Mechanical Engineering. The system consists
      of a two sided plate, one side is a non conducting adhesive surface to stick to
      the surgical glove and the other side is a subtle flexible shell of a conductor.
      The Authors used the instrument with surgical tools with a metallic handle,
      during three cholecystectomies. Nowadays all standard laparoscopic tools have the
      chance and the need to be electrified. Now the way commonly used to electrify a
      laparoscopic tool is using a wire plugged to a fixed conducting point of the
      instrument. This prototype has been devised and produced to avoid some
      discomforts met during the numerous manoeuvres of connecting and disconnecting
      the wire at the time of a surgical intervention. This device permits the direct
      transfer (by contact) of electric energy from the wire to surgical tools. The
      advantage is to be more rapid in changing surgical tools obtaining, immediately
      an electrified instrument in your hand.

PMID- 17211364
TI  - Coral spleen.

PMID- 17211365
TI  - Platelet-rich plasma treatment and hemostasis in patients with hemorrhagic risk.
AB  - AIM: Our research aimed to evaluate the risk of haemorrhage following oral
      surgical operations, in patients who were undergoing an anticoagulant therapy,
      and to test the usefulness of the autologous platelet gel in order to control
      haemostasis. METHODS: A total of 208 patients (84 males/124 females) undergoing
      an anticoagulant therapy and submitted to oral surgery, were divided at random
      into 4 groups (A, B, C, D) consisting of 52 patients each, using as criterion of
      differentiation the kind of treatment we adopted in order to get haemostasis. The
      patients belonging to the first 3 groups (A, B, C), underwent a surgical
      operation without discontinuing the dicumarol therapy. In order to get
      haemostasis, we used: platelet-rich plasma (PRP) and suture, in group A; PRP,
      haemostatic sponges and suture, in group B; haemostatic sponges, suture and
      compression by means of gauzes soaked in tranexamic acid in group C. Group D,
      instead, consisted of patients who underwent a surgical operation, before which
      the dicumarol therapy had been suspended and replaced by heparincalcium. RESULTS:
      Patients belonging to the groups A and B showed a very good haemostasis like the
      patients of group D (control group). As the coumarin therapy didn't need to be
      discontinued some days before the surgical operation, so the days of hospital
      stay were reduced and there wasn't the risk of thromboembolism. As to group C (19
      males), 6 patients (i.e. 11.5%) showed a good haemostasis, both at once and in
      the long term, so that they could be discharged on day 2 after surgery.
      CONCLUSIONS: The results obtained during our research, highly encourage using PRP
      regularly when carrying out surgical treatments on patients who are undergoing a
      coumarin therapy.

PMID- 17211366
TI  - Evaluation of the microtensile bond strength of composite resin restoration in
      dentin prepared with different sizes of aluminum oxide particles, using the air
      abrasion system.
AB  - AIM: The purpose of this in vitro study was to evaluate the influence of the
      abrasive technique on the microtensile bond strength of composite resin
      restorations. In addition, any differences in the microtensile bond strength were
      observed when different aluminum oxide particle sizes were used. METHODS: Flat
      coronal dentin surfaces were randomly distributed into 3 groups, according to
      surface treatment: Group A27 Air-abraded dentin with 27 microm aluminum oxide
      particles; Group A50-Air-abraded dentin with 50 microm aluminum oxide particles;
      Group HS cut dentin with a #1013 diamond bur in high-speed rotary instrument.
      After the bonding procedure (Single Bond/Z100), the teeth were stored in
      distilled water at 37 masculineC for 48 h prior to sectioning. Then, each bonded
      tooth was longitudinally sectioned producing sticks with a cross-sectional area
      of 0.81 mm2. The tensile load was applied at a crosshead speed of 0.5 mm/min,
      until the stick fractured. The data were analyzed by one-way ANOVA and post hoc
      multiple comparisons using Tukey's test. RESULTS: No difference was observed in
      composite bond strength when 27 and 50 microm aluminum oxide particles were used
      for dentin surface preparation using an air abrasion system. However, air-abraded
      dentin, using 27 microm aluminum oxide particles, demonstrated a higher bond
      strength when compared to dentin prepared by the conventional method (bur in high
      speed). CONCLUSIONS: The air-abraded dentin, using 27 microm alumina powder,
      demonstrated higher composite bond strength when compared to bur-cut dentin,
      raising the possibility that this method may increase restoration longevity.

PMID- 17211367
TI  - Histological investigation of a 10% metronidazole and 2% lidocaine dressing on
      wound healing in rats.
AB  - AIM: Alveolitis is considered a disturbance of the alveolar healing process that
      is characterized by blood clot disintegration, alveolar wall infection and
      extreme pain. Several substances have been investigated to improve healing and
      guarantee postoperative comfort to patients. The aim of this study was to
      evaluate, microscopically, in rats, the healing process in non-infected tooth
      sockets, after application of a 10% metronidazole and 2% lidocaine dressing,
      using lanolin as vehicle and mint as flavoring. METHODS: Forty-five rats (Rattus
      norvegicus albinus, Wistar) had their right incisor extracted and were randomly
      assigned to 3 groups (n=15): Group I (control): the sockets were filled with
      blood clot; Group II: application of adrenaline solution at 1:1 000 with an
      absorbent paper point during 1 min plus filling of the socket with a 10%
      metronidazole and 2% lidocaine dressing, with lanolin as vehicle, and mint as
      flavoring; Group III: filling of the socket with the 10% metronidazole and 2%
      lidocaine dressing, with lanolin as vehicle and mint as flavoring. After 6, 15
      and 28 days postoperatively, 5 animals per group were euthanized with an
      injectable anesthetic overdose. Histological and statistical analyses were
      performed. RESULTS: The results showed that the 10% metronidazole and 2%
      lidocaine dressing with lanolin as vehicle and mint as flavoring yielded similar
      response as that of the normal repair group and may be used to prevent the onset
      of alveolitis in those cases in which any predisposing factor is present.
      CONCLUSIONS: The use of this dressing has shown a good postoperative patient's
      comfort and does not cause a significant delay in the alveolar healing process.

PMID- 17211368
TI  - Otologic symptoms in temporomandibular disorders patients: is there evidence of
      an association-relationship?
AB  - Several studies in the literature investigated the association between
      temporomandibular disorders (TMD) and otogenous symptoms, like vertigo, tinnitus,
      otalgia and muffling, although the question of the existence of a cause-effect
      relationship is still controversial. Epidemiological findings showed that the
      prevalence of ear symptomatology in the general population is variable from 10%
      to 31%, and increases up to 85% in TMD patients. Based on these data, many
      attempts have been performed to describe the physiopathological interactions
      between aural symptoms and TMD, as a strict anatomical link exists between the
      structures of the ear and those of the stomatognathic system. Unfortunately,
      methodological weaknesses of most studies are evident so that the comparison of
      results is often difficult. Considering these premises, the present study
      critically reviewed the literature on this debated issue, discussing the main
      etiopathogenetic hypotheses, the features of ear symptomatology in TMD patients
      and its relationship with TMD treatment in order to present current suggestions
      about the relationship between aural and TMD symptoms. Suggestions for future
      researches have been also presented, since a full understanding of this plausible
      interaction will be an important factor in diagnosis making and treatment
      planning for both pathologies.

PMID- 17211369
TI  - Verruciform xanthoma of the oral mucosa. Report of a case.
AB  - Verruciform xanthoma is a rare benign lesion of unknown etiology and
      pathogenesis, although an inflammatory process seems to be implicated in its
      origin. It usually shows a slow-growing small lesion which can be sessile or
      pedunculated and has a typical rough and granular surface. A clinical case of an
      asymptomatic verruciform xanthoma of the ventral surface of the tongue in a 24
      year-old male is reported. The lesion was noticed for the first time during a
      routine dental examination and it appeared as a sessile whitish verrucous lump
      hard in texture. An incisional biopsy followed by the excision of the whole
      lesion was performed. The histological and immunohistochemistry examinations were
      carried out using antibodies CD68-KP1, CD68-PGM1, alpha-1-antitrypsin and
      vimentin, desmin, cytokeratins, NSE and S-100. Histology showed epithelial
      degeneration. The connective tissue papillae were entirely occupied by foamy
      cells that were positive for CD68-KP1, CD68-PGM1, alpha-1-antitrypsin and
      vimentin and negative for desmin, cytokeratins, NSE and S-100. The foamy cells
      were characterized by a large granulous cytoplasm and small picnotic nuclei. In
      accordance with the literature, the immunohistochemistry analysis confirmed that
      foamy cells are likely to have a macrophagic origin and that epithelial
      degeneration could be correlated with the pathogenesis of this lesion.

PMID- 17211370
TI  - Buccal-masseteric mycotic abscess as a consequence of dental procedures.
AB  - Trismus may represent an external sign of masticatory or lateral pharyngeal
      abscess that in rare cases is the consequence of pathogen action by micro
      organisms introduced in deep tissues after inferior alveolar block. The case
      presented shows a buccal-masseteric mycotic abscess following restorative
      procedure involving inferior alveolar anesthesia on the same side. A 49-year-old
      woman was referred to the Dental Clinic (University of Trieste) complaining of a
      progressive inability to open her mouth since one week associated to a hemifacial
      edema in the right parotid region. The symptoms initially started one week
      before. Infection developed after restorative procedures performed 10 days before
      on the same side. Based on clinical signs and cultural exam findings, a buccal
      masseteric mycotic abscess was found and magnetic resonance (MR) was performed to
      assess its localization and extension. Initial pharmacological therapy with
      piperacillin/tazobactam administered intravenously, was replaced by appropriate
      antimycotic therapy on the basis of sensitivity test to antibiotics. Infection
      resolution was obtained but complete absence of facial asymmetry occurred after 5
      months only. Introduction of micro-organisms during anesthetic alveolar block is
      a documented source of infection and may occur after dental procedure involving
      inferior alveolar anesthesia. Complete medical history, cultural exam with
      sensitivity test to antibiotics and RM or computed tomography (CT) images, are
      necessary to perform an adequate treatment plan and to administer a correct
      therapy. Presence of trismus, accompanied by pain or facial edema after dental
      procedure or during dental or perioral infections has to be carefully considered
      by clinician to diagnose as soon as possible a deep spaces infection and to avoid
      serious or life-threatening complications.

PMID- 17211372
TI  - The emperor's new clones.
AB  - If regulators conclude that food from clones poses no more risk than food from
      other animals, the US and Europe could be on course for another biotech trade
      war.

PMID- 17211373
TI  - Burning bridges.
AB  - A Wisconsin foundation's aggressive approach to patent licensing is damaging its
      reputation, compromising its own university's research collaborations and
      stymieing stem cell research.

PMID- 17211371
TI  - Local delivery of antimicrobial drugs in the treatment of chronic adult
      periodontitis.
AB  - AIM: The aim of this study was to evaluate the clinical and microbiologic results
      of local delivery of adjunctive antimicrobials in the treatment and management of
      patients with periodontitis. METHODS: The study population included 33 patients
      (age range, 37-49 years), with chronic adult periodontitis. Eleven of 33 received
      local treatment with 10% doxycycline injected directly into the periodontal
      pocket; 11 received local treatment with a chlorhexidine-based gel (1.5%) in
      situ; 11 received mechanical treatment with scaling and root planing. The
      crevicular fluid of the doxycycline-treated group was analyzed using high
      performance liquid chromatography over a period of 1 month. RESULTS: In the 11
      patients treated with an antibiotic we observed a reduction in attachment loss
      and a reduction in probing depth of 1.4 mm; in the 11 chlorhexidine-treated
      patients we observed a reduction in attachment loss and a reduction in probing
      depth of 0.9 mm; in the remaining 11 patients the reduction in attachment loss
      and probing depth was less than those measured in the other two treatment groups.
      CONCLUSIONS: Our results suggest that direct delivery of antimicrobial agents to
      the infection site may be a useful adjunctive to conventional periodontal
      treatment.

PMID- 17211374
TI  - Upward trend in financing continues, but fewer feel flush.

PMID- 17211375
TI  - Genentech makes its first-ever acquisition.

PMID- 17211376
TI  - Biotrin assay to monitor cervical cancer exposure rates.

PMID- 17211377
TI  - FDA's cloning report bypasses ethics, exposes European dilemma.

PMID- 17211379
TI  - Profile: Edmund D Pellegrino.

PMID- 17211380
TI  - Biotech as an employer.

PMID- 17211381
TI  - The policy outlook from the Hill.

PMID- 17211382
TI  - HDAC inhibitors overcome first hurdle.

PMID- 17211383
TI  - Statistical methods and microarray data.

PMID- 17211385
TI  - MAQC papers over the cracks.

PMID- 17211387
TI  - Unrealistic expectations for IR microspectroscopic imaging.

PMID- 17211389
TI  - Parallel biopolitical universes.

PMID- 17211390
TI  - Early-tier tests insufficient for GMO risk assessment.

PMID- 17211392
TI  - Animal cloning and the FDA--the risk assessment paradigm under public scrutiny.
AB  - The evidence gathered thus far--ultimately to be published in the Draft Risk
      Assessment on Animal Cloning--indicates that there are no unique risks associated
      with animal cloning.

PMID- 17211395
TI  - Dolly for dinner? Assessing commercial and regulatory trends in cloned livestock.
AB  - As cloning technologies become more widely established, will products enter the
      food chain sooner than regulatory agencies and the public might be prepared for?

PMID- 17211396
TI  - Japan's novelty grace period solves the dilemma of 'publish and perish'.

PMID- 17211397
TI  - Recent patent applications in antibodies.

PMID- 17211398
TI  - Laser surgery for mouse geneticists.

PMID- 17211399
TI  - Peptides you can count on.

PMID- 17211401
TI  - Evolving an anti-toxin antibody.

PMID- 17211400
TI  - A fluid means of stem cell generation.

PMID- 17211402
TI  - Lentiviral vectors ready for prime-time.

PMID- 17211403
TI  - Fungal gene clusters.

PMID- 17211405
TI  - Structure-based maximal affinity model predicts small-molecule druggability.
AB  - Lead generation is a major hurdle in small-molecule drug discovery, with an
      estimated 60% of projects failing from lack of lead matter or difficulty in
      optimizing leads for drug-like properties. It would be valuable to identify these
      less-druggable targets before incurring substantial expenditure and effort. Here
      we show that a model-based approach using basic biophysical principles yields
      good prediction of druggability based solely on the crystal structure of the
      target binding site. We quantitatively estimate the maximal affinity achievable
      by a drug-like molecule, and we show that these calculated values correlate with
      drug discovery outcomes. We experimentally test two predictions using high
      throughput screening of a diverse compound collection. The collective results
      highlight the utility of our approach as well as strategies for tackling
      difficult targets.

PMID- 17211406
TI  - Risk assessment of meat and milk from cloned animals.
AB  - Research on, and commercialization of, cloned cattle has been conducted for more
      than 20 years. Early techniques relied on the physical splitting of embryos or
      using embryo cells for nuclear transfer to generate cloned animals. Milk and meat
      from these animals entered into the human food market with no evidence of
      problems. With the advent of nuclear transfer, which enables the direct
      transference and preservation of high-value meat- and milk-producing genotypes to
      offspring, concerns have been raised about whether the products from somatic cell
      nuclear transfer-produced animals are safe for human consumption. Studies on the
      biochemical properties of food products from cloned and noncloned animals have
      thus far not detected any differences. All data to date indicate no significant
      differences in the measured parameters between animals created by nuclear
      transfer and normally bred animals. Public acceptance of cloned animal products
      depends upon forthcoming US Food and Drug Administration approval along with
      convincing safety data.

PMID- 17211407
TI  - Dimethyl sulfoxide to vorinostat: development of this histone deacetylase
      inhibitor as an anticancer drug.
AB  - In our quest to understand why dimethyl sulfoxide (DMSO) can cause growth arrest
      and terminal differentiation of transformed cells, we followed a path that led us
      to discover suberoylanilide hydroxamic acid (SAHA; vorinostat (Zolinza)), which
      is a histone deacetylase inhibitor. SAHA reacts with and blocks the catalytic
      site of these enzymes. Extensive structure-activity studies were done along the
      path from DMSO to SAHA. SAHA can cause growth arrest and death of a broad variety
      of transformed cells both in vitro and in tumor-bearing animals at concentrations
      not toxic to normal cells. SAHA has many protein targets whose structure and
      function are altered by acetylation, including chromatin-associated histones,
      nonhistone gene transcription factors and proteins involved in regulation of cell
      proliferation, migration and death. In clinical trials, SAHA has shown
      significant anticancer activity against both hematologic and solid tumors at
      doses well tolerated by patients. A new drug application was approved by the US
      Food and Drug Administration for vorinostat for treatment of cutaneous T-cell
      lymphoma. More potent analogs of SAHA have shown unacceptable toxicity.

PMID- 17211408
TI  - Masters of efficiency.
AB  - Manufacturing jobs may be shifting from the large drug companies to contract
      organizations as firms re-evaluate their strengths. But scientists with
      analytical skills and an eye for efficiency can find a job transforming materials
      into medicines.

PMID- 17211410
TI  - Wnt signaling and human diseases: what are the therapeutic implications?
AB  - Wnt signaling plays an important role in regulating cell proliferation and
      differentiation. De-regulation of these signaling pathways has been implicated in
      many human diseases, ranging from cancers to skeletal disorders. Wnt proteins are
      a large family of secreted factors that bind to the Frizzled receptors and LRP5/6
      co-receptors and initiate complex signaling cascades. Over the past two decades,
      our understanding of Wnt signaling has been significantly improved due to the
      identification of many key regulators and mediators of these pathways. Given that
      Wnt signaling is tightly regulated at multiple cellular levels, these pathways
      themselves offer ample nodal points for targeted therapeutics. Here, we focus on
      our current understanding of these pathways, the associations of Wnt signaling
      with human disorders, and the opportunities to target key components of Wnt
      signaling for rational drug discovery.

PMID- 17211411
TI  - Loss of osteopontin perturbs the epithelial-mesenchymal transition in an injured
      mouse lens epithelium.
AB  - We previously reported that osteopontin (OPN), a matrix structural
      glycophosphoprotein, is upregulated in the injured mouse lens prior to the
      epithelial-mesenchymal transition (EMT). Here, we investigated the role of this
      protein in EMT of the lens epithelium during wound healing. The crystalline lens
      was injured by needle puncture in OPN-null (KO, n=40) and wild-type (WT, n=40)
      mice. The animals were killed at day 1, 2, 5, and 10 postinjury.
      Immunohistochemistry was employed to detect alpha-smooth muscle action
      (alphaSMA), a marker of EMT, collagen type I, transforming growth factor beta1
      (TGFbeta1), TGFbeta2, and phospho-Smad2/3. Cell proliferation was assayed by
      examining uptake of bromodeoxyuridine (BrdU). The results showed that injury
      induced EMT of mouse lens epithelium, as evaluated by histology, expression
      pattern of alphaSMA and collagen I, was altered in the absence of OPN with
      reduced phospho-Smad2/3 signaling. Upregulation of TGFbeta1 and TGFbeta2 in the
      epithelium was also inhibited. Cell proliferation was more active in KO mice as
      compared with WT mice at day 1 and 2, but not at day 5 and 10. An in vitro
      experiment shows OPN facilitates cell adhesion of lens epithelial cell line. OPN
      is required for activation of Smad2/3 signal in an injured lens epithelium and
      lens cell EMT.

PMID- 17211413
TI  - The responsible use of antibiotics for an elevated PSA level.

PMID- 17211414
TI  - The role of surveillance for small renal masses.

PMID- 17211412
TI  - A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA
      hypermethylation and heritable silencing.
AB  - Adult cancers may derive from stem or early progenitor cells. Epigenetic
      modulation of gene expression is essential for normal function of these early
      cells but is highly abnormal in cancers, which often show aberrant promoter CpG
      island hypermethylation and transcriptional silencing of tumor suppressor genes
      and pro-differentiation factors. We find that for such genes, both normal and
      malignant embryonic cells generally lack the hypermethylation of DNA found in
      adult cancers. In embryonic stem cells, these genes are held in a 'transcription
      ready' state mediated by a 'bivalent' promoter chromatin pattern consisting of
      the repressive mark, histone H3 methylated at Lys27 (H3K27) by Polycomb group
      proteins, plus the active mark, methylated H3K4. However, embryonic carcinoma
      cells add two key repressive marks, dimethylated H3K9 and trimethylated H3K9,
      both associated with DNA hypermethylation in adult cancers. We hypothesize that
      cell chromatin patterns and transient silencing of these important regulatory
      genes in stem or progenitor cells may leave these genes vulnerable to aberrant
      DNA hypermethylation and heritable gene silencing during tumor initiation and
      progression.

PMID- 17211415
TI  - Degree of fetal renal pelvic dilatation predicts postnatal obstruction.

PMID- 17211416
TI  - Is a second transurethral resection necessary in T1 bladder cancer?

PMID- 17211417
TI  - Home uroflowmetry biofeedback therapy for dysfunctional voiding in school-age
      children.

PMID- 17211418
TI  - Smoking, obesity, and sedentary lifestyle linked to erectile dysfunction.

PMID- 17211419
TI  - Dose-response in external-beam radiotherapy for prostate cancer: the evidence
      grows.

PMID- 17211420
TI  - Does early androgen deprivation therapy improve outcome after radical
      prostatectomy?

PMID- 17211421
TI  - Is intralesional interferon alpha2b a safe and effective minimally invasive
      treatment for Peyronie's disease?

PMID- 17211422
TI  - Radiation-sensitizing chemotherapy after transurethral resection as an
      alternative treatment for high-risk T1 bladder cancer.

PMID- 17211423
TI  - Minimally invasive surgery for urologic disease in children.
AB  - This article is a comprehensive review of the current indications and recent
      literature pertaining to laparoscopic techniques in pediatric urology. Basic
      concepts such as instrumentation, anesthetic considerations, and complications
      are reviewed. Specific techniques and indications are also explored. As the field
      of pediatric urology continues to expand, it still lags behind adult urology.
      With improvements in technology, however, and with new surgeons entering the
      field with a basic laparoscopic background, pediatric urologic laparoscopy
      continues to progress. Currently, procedures such as laparoscopic exploration for
      undescended testicles and laparoscopic nephrectomy are accepted as the 'gold
      standard', and are performed at most institutions. Other procedures, such as
      laparoscopic pyeloplasty and laparoscopic reconstructive surgery, have only
      recently been introduced and are primarily available at centers with surgeons
      experienced in laparoscopy. It is our hope that minimally invasive surgical
      approaches to urologic conditions will become available to all children and
      become commonplace at most institutions.

PMID- 17211424
TI  - Technology insight: will systems pathology replace the pathologist?
AB  - By using systems pathology, it might be possible to provide a predictive,
      personalized therapeutic recommendation for patients with prostate cancer.
      Systems pathology integrates quantitative data and information from many sources
      to generate a reliable prediction of the expected natural course of the disease
      and response to different therapeutic options. In other words, through the
      integration of relatively large data sets and the use of knowledge engineering,
      systems pathology aims at predicting the future behavior of tumors and their
      interaction with the host. In this Review, we introduce the methods used in
      systems pathology and summarize a recent study providing the first evidence of a
      concept for this strategy. The results show that systems pathology can provide a
      personalized prediction of the risk of recurrence after prostatectomy for cancer.

PMID- 17211426
TI  - Urogenital prolapse and occult stress urinary incontinence.
AB  - BACKGROUND: A 76-year-old female presented to an outside clinic with symptoms of
      pelvic prolapse; she denied stress urinary incontinence (SUI). The patient had a
      history of two prior anti-incontinence surgeries. Pelvic examination revealed a
      grade IV cystocele. No SUI was identified, with or without reduction of the
      prolapse. Anterior colporrhaphy with cadaveric fascia was performed. Her prolapse
      symptoms resolved, but she had new-onset severe SUI. INVESTIGATIONS: Pelvic
      examination, cystoscopy, urodynamics. DIAGNOSIS OCCULT: SUI unmasked after
      anterior colporrhaphy. MANAGEMENT: The patient was referred to our institution
      where videourodynamics were performed, revealing a well-supported bladder and SUI
      with Valsalva leak-point pressure of 26 cm H20. A transvaginal polypropylene
      sling was placed. She had complete resolution of SUI and denied exacerbation of
      mild urgency.

PMID- 17211425
TI  - Mechanisms of disease: involvement of the urothelium in bladder dysfunction.
AB  - Although the urinary bladder urothelium has classically been thought of as a
      passive barrier to ions and solutes, a number of novel properties have been
      recently attributed to urothelial cells. Studies have revealed that the
      urothelium is involved in sensory mechanisms (i.e. the ability to express a
      number of sensor molecules or respond to thermal, mechanical and chemical
      stimuli) and can release chemical mediators. Localization of afferent nerves next
      to the urothelium suggests that urothelial cells could be targets for
      neurotransmitters released from bladder nerves or that chemicals released by
      urothelial cells could alter afferent nerve excitability. Taken together, these
      and other findings highlighted in this article suggest a sensory function for the
      urothelium. Elucidation of mechanisms that influence urothelial function might
      provide insights into the pathology of bladder dysfunction.

PMID- 17211427
TI  - Rigorous administration of methotrexate and outcome of allogeneic blood stem cell
      transplantation.

PMID- 17211428
TI  - A case of 'red eye' post allogeneic stem cell transplantation.

PMID- 17211429
TI  - Salvage with a mini-allograft after primary engraftment failure following
      autologous transplant for multiple myeloma.

PMID- 17211430
TI  - Therapeutic effect of umbilical cord serum eyedrops for the treatment of dry eye
      associated with graft-versus-host disease.
AB  - This study was performed to investigate the therapeutic effect of umbilical cord
      serum eyedrops on dry eye associated with graft-versus-host disease (GVHD).
      Twenty-four eyes of 12 patients with severe dry eye syndrome associated with GVHD
      were treated with 20% umbilical cord serum eyedrops. Symptom scoring, corneal
      sensitivity test, tear film break up time (BUT), Schirmer test, tear clearance
      rate (TCR), and corneal fluorescein staining were performed before and 2 and 6
      months after treatment. Six months after treatment, significant improvement was
      observed in symptom score (from 3.83+/-0.38 to 0.83+/-0.57, P<0.01), corneal
      sensitivity (from 52.08+/-6.06 mm to 57.50+/-3.00 mm, P<0.01), tear film BUT
      (from 2.50+/-0.91 s to 5.71+/-1.04 s, P<0.01), and keratoepitheliopathy score
      (from 7.42+/-2.02 to 1.29+/-0.46, P<0.01). There was no siginificant change in
      Schirmer test and TCR results. No significant complications associated with the
      use of the eyedrops were observed. Umbilical cord serum eyedrops are safe and may
      be an effective way to treat severe dry eye associated with GVHD.

PMID- 17211431
TI  - F-ara-A pharmacokinetics during reduced-intensity conditioning therapy with
      fludarabine and busulfan.
AB  - Fludarabine is commonly used in combination with busulfan as part of conditioning
      regimens before allogeneic stem cell transplantation. So far, no data are
      available on busulfan-fludarabine drug interactions in transplant recipients. The
      pharmacokinetic (PK) properties of F-ara-A (9-beta-D-arabinosyl-2-fluoradenine)
      before and after application of busulfan were prospectively investigated in 16
      patients with hematological malignancies. The conditioning regimen consisted of
      intravenous fludarabine 30 mg/m(2) over 30 min from day -6 to day -3, and oral
      busulfan given at 1 mg/kg every 6 h from day -5 to day -2. PK parameters of F-ara
      A, derived from plasma and urine on day -6, -5, -4 and -3, were determined using
      high-performance liquid chromatography (HPLC). AUC, C(max), t(1/2), Cl(total) and
      V(SS) were 21.9 microMh, 3.5 microM, 13.0 h, 4.3 l/h/m(2), 60.0 l/m(2) on day -6
      and 22.4 microMh, 3.5 microM, 14.0 h, 4.7 l/h/m(2), 69.0 l/m(2) on day -5 to (
      2), respectively. Cl(renal) and the urine-recovery were 4.8 l/h, 43.7% of the
      fludarabine dose on day -6 and 3.9 l/h, 44.2% of the fludarabine dose on day -5
      to (-2), respectively. There were no changes in PK parameters of fludarabine
      given before and after intake of busulfan. This implies that a clinically
      relevant busulfan-fludarabine drug interaction is unlikely.

PMID- 17211432
TI  - A randomized study on donor immunization with tetanus-diphtheria, Haemophilus
      influenzae type b and inactivated poliovirus vaccines to improve the recipient
      responses to the same vaccines after allogeneic bone marrow transplantation.
AB  - The HLA-identical sibling donors of 111 bone marrow transplantation (BMT)
      recipients were randomised to receive or not to receive tetanus-diphtheria (T-d),
      Haemophilus influenzae type b (Hib), and inactivated poliovirus (IPV) vaccines 2
      10 weeks before BM harvest. Fifty-three (DV+ group) recipients received the graft
      from a vaccinated donor and 58 (DV- group) from an unvaccinated donor. All
      recipients were vaccinated with the T-d, Hib and IPV vaccines at 3, 6 and 12
      months after BMT. Diphtheria and Hib antibody concentrations were consistently
      higher in the DV+ than in the DV- group from 6 months post transplantation
      onwards. The differences were significant at 6 and 13 months for diphtheria and
      at 12 months for Hib antibody concentrations. Tetanus, PV1, PV2 and PV3 antibody
      levels were similar in both groups. Patients transplanted from donors with high
      tetanus, diphtheria and Hib antibody concentrations had higher respective
      antibody concentrations after BMT than those transplanted from donors with low
      antibody concentrations. Especially patients whose donors have low-specific
      antibody concentrations may benefit from donor vaccination with protein and
      conjugate vaccines.

PMID- 17211433
TI  - Cytogenetic evolution patterns in CML post-SCT.
AB  - The cytogenetic evolution patterns in chronic myeloid leukemia (CML) after
      allogeneic (allo) stem cell transplantation (SCT) are different from the ones
      observed in non-transplanted patients, a phenomenon suggested to be caused by the
      conditioning regime. We reviewed 131 CMLs displaying karyotypic evolution after
      SCT (122 allo, nine autologous (auto)), treated at Lund University Hospital or
      reported in the literature. Major route abnormalities (i.e., +8, +Ph, i(17q),
      +19, +21, +17 and -7) were seen in 14%, balanced aberrations in 61%,
      hyperdiploidy in 19%, pseudodiploidy in 79%, divergent clones in 14%, and Ph
      negative clones in 21%. The breakpoints involved in secondary structural
      rearrangements clustered at 1q21, 1q32, 7q22, 9q34, 11q13, 11q23, 12q24, 13q14,
      17q10 and 22q11. Cytogenetic abnormalities common in AML after genotoxic
      exposure, that is, der(1;7)(q10;p10), del(3p), -5, del(5q), -7, -17, der(17p), 
      18, and -21, were only rarely seen post-SCT. Comparing the cytogenetic features
      in relation to type of SCT revealed that balanced aberrations were significantly
      more common after allo than after auto SCT (64 and 22%, respectively, P=0.03). In
      addition, there was a trend as regards hyperdiploidy being more common after auto
      (P=0.07) and pseudodiploidy being more frequent after allo SCT (P=0.09). Possible
      reasons for these differences are discussed.

PMID- 17211434
TI  - The effect of quantification standards used in real-time CMV PCR assays on
      guidelines for initiation of therapy in allogeneic stem cell transplant patients.

PMID- 17211435
TI  - T cell regeneration in pediatric allogeneic stem cell transplantation.
AB  - Delayed and/or insufficient T cell recovery post hematopoietic stem cell
      transplantation (HSCT) leads to an increased risk of morbidity and mortality. We
      evaluated thymic function and its association with T cell regeneration post HSCT
      and identified factors involved in the process among pediatric stem cell
      transplant recipients. T cell regeneration in 66 pediatric patients was
      prospectively followed by naive T cell phenotyping, measuring of T cell receptor
      excision circles (TRECs) and expression of Foxp3 by regulatory T cells for the
      first 18 months post HSCT. TRECs were lower pre-HSCT in children with a malignant
      than non-malignant primary disease or immunosuppressed controls (P=0.001). Naive
      T lymphocyte reconstitution and thymic recovery were slow in the recipients of
      allogeneic stem cell grafts post HSCT. Infections caused by herpesviruses had a
      prognostic impact on mortality. Children with low TRECs had a high mortality
      (P=0.05) and low TRECs were also associated with extensive chronic graft-versus
      host disease from 6 months onwards. Low amount of Foxp3 pre-HSCT was associated
      with an increased mortality post HSCT (P=0.03). Our study indicates an
      association between impaired T cell regeneration and thymic dysfunction and the
      clinical post transplant complications in pediatric allogeneic stem cell
      transplantation.

PMID- 17211436
TI  - Imatinib therapy for chronic myeloid leukemia patients who relapse after
      allogeneic stem cell transplantation: a molecular analysis.

PMID- 17211437
TI  - Substitution of cyclophosphamide and busulfan by fludarabine, treosulfan and
      melphalan in a preparative regimen for children and adolescents with Shwachman
      Diamond syndrome.
AB  - Allogeneic hematopoietic stem cell transplantation (HSCT) is the only definitive
      treatment for severe bone marrow dysfunction and clonal disorders in patients
      diagnosed with Shwachman-Diamond syndrome (SDS). In an attempt to minimize
      regimen-related toxicity (RRT), we have initiated a
      fludarabine/treosulfan/melphalan-based pilot protocol avoiding the combination of
      busulfan and cyclophosphamide. Median age at transplantation was 9.6 years (range
      1.5-17 years). All three patients received conditioning with fludarabine (30
      mg/m2/day x 6), treosulfan (12 g/m2/day x 3) and melphalan (140 mg/m2/day x 1).
      CAMPATH-1H (0.1 mg/kg x 2) was added in two cases, while rabbit ATG (Genzyme; 3 x
      2.5 mg/kg) was given to the cord blood recipient. One patient was transplanted
      with a non-manipulated marrow graft from an HLA-identical sibling, one with a
      marrow graft from a 10/10 matched unrelated donor, and one with a 9/10 matched
      unrelated umbilical cord blood (UCB) unit. Mean cell doses given were 3.6 x 10(8)
      nucleated cells/kg BW for the bone marrow recipients and 4.2 x 10(7) nucleated
      cells/kg BW for UCB recipient. Overall, two of three patients are alive and
      display 100% donor chimerism. Acute graft-versus-host disease grade II was seen
      in one patient, while no GVHD exceeding grade I occurred in the remaining two.

PMID- 17211438
TI  - Alterations of lipid metabolism and gene expression in rat adipocytes during
      chronic olanzapine treatment.
AB  - Although antipsychotics are established drugs in schizophrenia treatment, they
      are admittedly known to induce side effects favoring the onset of obesity and
      worsening its complications. Despite potential involvement of histamine receptor
      antagonism, or of other neurotransmitter systems, the mechanism by which
      antipsychotic drugs increase body weight is not elucidated. The aim of the
      present study was to investigate whether chronic antipsychotic treatments can
      directly alter the regulation of two main functions of white adipose tissue:
      lipolysis and glucose utilization. The influence of a classical antipsychotic
      (haloperidol) was compared to that of two atypical antipsychotics, one known to
      favor weight gain (olanzapine), the other not (ziprasidone). Cell size, lipolytic
      capacity and glucose transport activity were determined in white adipocytes of
      rats subjected to 5-week oral treatment with these antipsychotics. Gene
      expression of adipocyte proteins involved in glucose transport or fat storage and
      mobilization, such as glucose transporters (GLUT1 and GLUT4), leptin, matrix
      metallo-proteinase-9 (MMP9), hormone-sensitive lipase (HSL) and fatty acid
      synthase (FAS) was also evaluated. Adipocytes from chronic olanzapine-treated
      rats exhibited decreased lipolytic activity, lowered HSL expression and increased
      FAS expression. These changes were concomitant to enlarged fat deposition and
      adipocyte size. Alterations were observed in adipocytes from olanzapine-treated
      rats whereas the other antipsychotics did not induce any notable disorder. Our
      results therefore show evidence of an effect of chronic antipsychotic treatment
      on rat adipocyte metabolism. Thus, impairment of fat cell lipolysis should be
      considered as a side effect of certain antipsychotics, leading, along with the
      already documented hyperphagia, to the excessive weight gain observed in patients
      under prolonged treatment..

PMID- 17211439
TI  - Gene-gene effects on central processing of aversive stimuli.
AB  - Emotional reactivity and regulation are fundamental to human behavior. As inter
      individual behavioral variation is affected by a multitude of different genes,
      there is intense interest to investigate gene-gene effects. Functional sequence
      variation at two genes has been associated with response and resiliency to
      emotionally unpleasant stimuli. These genes are the catechol-O-methyltransferase
      gene (COMT Val158Met) and the regulatory region (5-HTTLPR) of the serotonin
      transporter gene. Recently, it has been proposed that 5-HTT expression is not
      only affected by the common S/L variant of 5-HTTLPR but also by an A to G
      substitution. Using functional magnetic resonance imaging, we assessed the
      effects of COMT Val(158)Met and both 5-HTT genotypes on brain activation by
      standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 48
      healthy subjects. Based on previous studies, the analysis of genotype effects was
      restricted to limbic brain areas. To determine allele-dose effects, the number of
      COMT Met158 alleles (i.e., lower activity of COMT) and the number of 5-HTT low
      expressing alleles (S and G) was correlated with the blood oxygen level-dependent
      (BOLD) response to pleasant or unpleasant stimuli compared to neutral stimuli. We
      observed an additive effect of COMT and both 5-HTT polymorphisms, accounting for
      40% of the inter-individual variance in the averaged BOLD response of amygdala,
      hippocampal and limbic cortical regions elicited by unpleasant stimuli. Effects
      of 5-HTT and COMT genotypes did not affect brain processing of pleasant stimuli.
      These data indicate that functional brain imaging may be used to assess the
      interaction of multiple genes on the function of neuronal networks.

PMID- 17211440
TI  - Lack of survival benefit of post-operative radiation therapy in prostate cancer
      patients with positive lymph nodes.
AB  - Randomized data from SWOG 8794 and EORTC 22911 confirm the benefit of post
      operative radiation therapy (RT) for selected patients with pT3 prostate cancer
      (CaP) after radical prostatectomy (RP). However, data regarding the potential
      benefit of RT for patients post-RP with positive lymph node (+LN) involvement are
      limited. We analyzed the Surveillance Epidemiology End Results (SEER) registry
      for population-based data on efficacy of post-operative RT for +LN patients after
      RP. As LN data have only been captured by SEER since 1988, we analyzed data for
      1988-1992, with specific attention to 10-year relative survival (defined as
      observed survival divided by the survival of a gender-, age- and race-matched
      population cohort without disease). Specifically analyzed were data for 1921
      patients with nonmetastatic prostate cancer who underwent surgery alone, or
      surgery followed by RT, and who had +LNs documented. SEER does not code the
      interval between surgery and RT, so the ratio of patients receiving salvage
      versus adjuvant therapy is unknown. Using follow-up data through 2002, post
      diagnosis survival was examined by number of +LNs. There was no significant
      relative survival benefit for +LN patients receiving post-operative RT
      (chi(2)P=0.270). These data do not support routine use of post-operative RT for
      patients with +LNs in the surgical specimen.

PMID- 17211441
TI  - A meta-analysis of local anesthesia for transrectal ultrasound-guided biopsy of
      the prostate.
AB  - This meta-analysis evaluated the efficacy and safety of periprostatic nerve block
      (PPNB) and intrarectal local anesthestic (IRLA) gel in alleviating pain during
      prostate biopsy. Electronic databases MEDLINE, Cochrane Central Register of
      Controlled Trials and EMBASE were searched to identify all randomized controlled
      trials comparing PPNB with periprostatic placebo injection, no injection or with
      IRLA. Studies for inclusion were identified and extracted by two authors
      independently. The main outcome measure was patients' assessment of mean pain
      scores on a 10-point scale at the end of the biopsy procedure. Secondary outcomes
      were complications and adverse events. Continuous data from the trials were
      combined by calculating the weighted mean difference (WMD) with its 95%
      confidence interval. In total, 25 studies met the inclusion criteria. Twenty
      studies involving 1685 patients compared PPNB with either no anesthesia or with
      placebo injection controls, showing a significant reduction in pain score in the
      anesthetic group (WMD -2.09, 95% CI -2.44 to -1.75, P<0.00001). Five studies with
      466 patients compared IRLA and control. Although IRLA was associated with pain
      reduction, the effect size was not statistically significant (WMD -0.22, 95% CI 
      0.56 to 0.12). Six studies with 872 patients compared PPNB with IRLA, showing a
      significant pain reduction in the former group (WMD -1.53, 95% CI -2.67 to -0.39,
      P=0.008). No trials reported an increase in complications in the treatment arms.
      In conclusion, the evidence from randomized controlled trials shows that local
      anesthetic given as a PPNB, but not as an intrarectal instillation, is effective
      and safe in alleviating pain from transrectal ultrasound biopsy of the prostate.

PMID- 17211442
TI  - Rapid onset of action with alfuzosin 10 mg once daily in men with benign
      prostatic hyperplasia: a randomized, placebo-controlled trial.
AB  - This randomized, double-blind, placebo-controlled study was conducted to
      investigate whether alfuzosin 10 mg once daily improves the maximum flow rate
      (Q(max)) and lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia
      (BPH) after 1 week and 1 month of treatment. A total of 372 men aged > or = 50
      years with symptomatic BPH received alfuzosin or placebo for 28 days. Q(max)
      increased significantly from baseline at day 8 with alfuzosin (P<0.001 versus
      placebo); this improvement was evident within 24 h after the first dose and was
      maintained at day 29. LUTS improved from baseline with alfuzosin at day 8 (P=0.07
      versus placebo) and day 29 (P=0.003 versus placebo). Alfuzosin 10 mg once daily
      exhibits a rapid onset of action, with improvements in Q(max) and LUTS maintained
      through 1 month of treatment.

PMID- 17211443
TI  - Overweight/obesity and attention deficit and hyperactivity disorder tendency
      among adolescents in China.
AB  - OBJECTIVE: This study aims to investigate whether there is any association
      between attention deficit hyperactivity disorder (ADHD) tendency and
      overweight/obesity among adolescents. DESIGN: This study was a population-based
      health survey utilizing a two-stage random cluster sampling design. SUBJECTS:
      Subjects were recruited from the total population of adolescents who attended
      high school years 1, 2 and 3 with ages ranging from 13 to 17 years. MEASUREMENTS:
      Individual body weight and height were measured by medical professionals.
      Overweight and obesity were determined according to the CDC classification. ADHD
      tendency was assessed via a structured personal interview using a standardised
      scale. RESULTS: In all, 1429 students were recruited with 85 (6.3%) classified
      overweight and 42 (3.1%) obese with a mean BMI score of 19.1 (s.e.=0.15). For
      ADHD tendency, the average score was 15.48 (s.e.=0.28) with a median score of
      16.0. There was a significant association between ADHD tendency and obesity among
      these adolescent (t=2.18, P=0.040), after adjusting for the potential confounding
      factors. However, the association between ADHD tendency and overweight did not
      reach a significant level. CONCLUSION: ADHD tendency is associated with
      overweight/obesity among adolescents. Clinician should be aware of the increased
      risk of ADHD among obese adolescents. ADHD should be assessed and proper
      treatment should be provided in the management of obese.

PMID- 17211444
TI  - Adipocyte-derived products induce the transcription of the StAR promoter and
      stimulate aldosterone and cortisol secretion from adrenocortical cells through
      the Wnt-signaling pathway.
AB  - CONTEXT: Obesity is associated with hypersecretion of cortisol and aldosterone
      and a high prevalence of arterial hypertension. At the cellular level, a direct
      effect of adipocytes on the expression of the steroidogenic acute regulatory
      (StAR) protein, a regulator of cortisol and aldosterone synthesis, and on
      aldosterone and cortisol secretion has been shown. However, the molecular
      mechanisms mediating this effect are not known. OBJECTIVE: Wnt-signaling
      molecules are secreted by adipocytes and regulate the activity of SF-1, a key
      transcription factor in adrenal steroidogenesis. Therefore, we investigated
      whether adipocytes stimulate adrenal steroidogenesis through the activation of
      Wnt-signaling. RESULTS: Using immunohistochemistry, we detected the expression of
      frizzled and beta-catenin in the adult human adrenal cortex. Transient
      transfection of a Wnt-dependent reporter-gene into adrenal NCI-H295R cells showed
      an induction of Wnt-mediated transcription to 308% after treatment with human fat
      cell-conditioned medium (FCCM). This finding was paralleled by an induction of
      StAR promoter activity (420%) by FCCM. The induction of StAR promoter activity by
      FCCM was inhibited by 49% when Wnt-signaling was blocked by the soluble Wnt
      antagonist secreted Frizzled-Related-Protein-1 (sFRP-1). Overexpression of a
      constitutively active mutant of beta-catenin induced the transcription of the
      StAR promoter (440%). beta-Catenin and FCCM induced SF-1-mediated transcription
      at a SF-1-driven reporter gene (420 and 402%, respectively). Furthermore, the
      secretion of aldosterone and cortisol by NCI-H295R cells induced by FCCM was
      significantly inhibited by the Wnt-antagonist sFRP-1. CONCLUSION: These data
      indicate that the Wnt-signaling pathway is one of the mechanisms mediating the
      effects of fat cells on adrenal StAR transcription and aldosterone and cortisol
      secretion.

PMID- 17211445
TI  - Getting the right stuff: controlling neural stem cell state and fate in vivo and
      in vitro with biomaterials.
AB  - Stem cell therapy holds great promises in medical treatment by, e.g., replacing
      lost cells, re-constitute healthy cell populations and also in the use of stem
      cells as vehicles for factor and gene delivery. Embryonic stem cells have
      rightfully attracted a large interest due to their proven capacity of
      differentiating into any cell type in the embryo in vivo. Tissue-specific stem
      cells are however already in use in medical practice, and recently the first
      systematic medical trials involving human neural stem cell (NSC) therapy have
      been launched. There are yet many obstacles to overcome and procedures to
      improve. To ensure progress in the medical use of stem cells increased basic
      knowledge of the molecular mechanisms that govern stem cell characteristics is
      necessary. Here we provide a review of the literature on NSCs in various aspects
      of cell therapy, with the main focus on the potential of using biomaterials to
      control NSC characteristics, differentiation, and delivery. We summarize results
      from studies on the characteristics of endogenous and transplanted NSCs in rodent
      models of neurological and cancer diseases, and highlight recent advancements in
      polymer compatibility and applicability in regulating NSC state and fate. We
      suggest that the development of specially designed polymers, such as hydrogels,
      is a crucial issue to improve the outcome of stem cell therapy in the central
      nervous system.

PMID- 17211446
TI  - Shp2-mediated molecular signaling in control of embryonic stem cell self-renewal
      and differentiation.
AB  - A key issue to be addressed in stem cell biology is the molecular signaling
      mechanism controlling embryonic stem (ES) cell pluripotency. Stem cell properties
      are dictated by specific transcription factors and epigenetic processes such as
      DNA methylation and chromatin remodeling. Several cytokines/growth factors have
      been identified as critical ES cell regulators. However, there is a gap in our
      knowledge of the intracellular signaling pathways linking extracellular signals
      to transcriptional regulation in ES cells. This short review discusses the
      physiological role of Shp2, a cytoplasmic tyrosine phosphatase, in the molecular
      switch governing ES cell self-renewal versus differentiation. Shp2 promotes ES
      cell differentiation, mainly through bi-directional modulation of Erk and Stat3
      pathways. Deletion of Shp2 in mouse ES cells results in more efficient self
      renewal. This observation provides the impetus to develop Shp2 inhibitors for
      maintenance and amplification of ES cells in culture.

PMID- 17211447
TI  - Establishment of customized mouse stem cell lines by sequential nuclear transfer.
AB  - Therapeutic cloning, whereby embryonic stem cells (ESCs) are derived from nuclear
      transfer (NT) embryos, may play a major role in the new era of regenerative
      medicine. In this study we established forty nuclear transfer-ESC (NT-ESC) lines
      that were derived from NT embryos of different donor cell types or passages. We
      found that NT-ESCs were capable of forming embryoid bodies. In addition, NT-ESCs
      expressed pluripotency stem cell markers in vitro and could differentiate into
      embryonic tissues in vivo. NT embryos from early passage R1 donor cells were able
      to form full term developed pups, whereas those from late passage R1 ES donor
      cells lost the potential for reprogramming that is essential for live birth. We
      subsequently established sequential NT-R1-ESC lines that were developed from NT
      blastocyst of late passage R1 ESC donors. However, these NT-R1-ESC lines, when
      used as nuclear transfer donors at their early passages, failed to result in live
      pups. This indicates that the therapeutic cloning process using sequential NT
      ESCs may not rescue the developmental deficiencies that resided in previous donor
      generations.

PMID- 17211448
TI  - Promoting human embryonic stem cell renewal or differentiation by modulating Wnt
      signal and culture conditions.
AB  - We previously showed that Wnt3a could stimulate human embryonic stem (hES) cell
      proliferation and affect cell fate determination. In the absence of feeder cell
      derived factors, hES cells cultured under a feeder-free condition survived and
      proliferated poorly. Adding recombinant Wnt3a in the absence of feeder cell
      derived-factors stimulated hES cell proliferation but also differentiation. In
      the present study, we further extended our analysis to other Wnt ligands such as
      Wnt1 and Wnt5a. While Wnt1 displayed a similar effect on hES cells as Wnt3a,
      Wnt5a had little effect in this system. Wnt3a and Wnt1 enhanced proliferation of
      undifferentiated hES cells when feeder-derived self-renewal factors and bFGF are
      also present. To explore the possibility to promote the proliferation of
      undifferentiated hES cells by activating the Wnt signaling, we overexpressed
      Wnt3a or Wnt1 gene in immortalized human adult fibroblast (HAFi) cells that are
      superior in supporting long-term growth of undifferentiated hES cells than
      primary mouse embryonic fibroblasts. HAFi cells with or without a Wnt transgene
      can be propagated indefinitely. Over-expression of the Wnt3a gene significantly
      enhanced the ability of HAFi feeder cells to support the undifferentiated growth
      of 3 different hES cell lines we tested. Co-expression of three commonly-used
      drug selection genes in Wnt3a-overpressing HAFi cells further enabled us to
      select rare hES clones after stable transfection or transduction. These
      immortalized engineered feeder cells (W3R) that co-express growth-promoting genes
      such as Wnt3a and three drug selection genes should empower us to efficiently
      make genetic modified hES cell lines for basic and translational research.

PMID- 17211451
TI  - Nanog and transcriptional networks in embryonic stem cell pluripotency.
AB  - Several extrinsic signals such as LIF, BMP and Wnt can support the self-renewal
      and pluripotency of embryonic stem (ES) cells through regulating the "pluripotent
      genes." A unique homeobox transcription factor, Nanog, is one of the key
      downstream effectors of these signals. Elevated level of Nanog can maintain the
      mouse ES cell self-renewal independent of LIF and enable human ES cell growth
      without feeder cells. In addition to the external signal pathways, intrinsic
      transcription factors such as FoxD3, P53 and Oct4 are also involved in regulating
      the expression of Nanog. Functionally, Nanog works together with other key
      pluripotent factors such as Oct4 and Sox2 to control a set of target genes that
      have important functions in ES cell pluripotency. These key factors form a
      regulatory network to support or limit each other's expression level, which
      maintains the properties of ES cells.

PMID- 17211450
TI  - Upregulation of Flk-1 by bFGF via the ERK pathway is essential for VEGF-mediated
      promotion of neural stem cell proliferation.
AB  - Neural stem cells (NSCs) constitute the cellular basis for embryonic brain
      development and neurogenesis. The process is regulated by NSC niche including
      neighbor cells such as vascular and glial cells. Since both vascular and glial
      cells secrete vascular endothelial growth factor (VEGF) and basic fibroblast
      growth factor (bFGF), we assessed the effect of VEGF and bFGF on NSC
      proliferation using nearly homogeneous NSCs that were differentiated from mouse
      embryonic stem cells. VEGF alone did not have any significant effect. When bFGF
      was added, however, VEGF stimulated NSC proliferation in a dose-dependent manner,
      and this stimulation was inhibited by ZM323881, a VEGF receptor (Flk-1)-specific
      inhibitor. Interestingly, ZM323881 also inhibited cell proliferation in the
      absence of exogenous VEGF, suggesting that VEGF autocrine plays a role in the
      proliferation of NSCs. The stimulatory effect of VEGF on NSC proliferation
      depends on bFGF, which is likely due to the fact that expression of Flk-1 was
      upregulated by bFGF via phosphorylation of ERK1/2. Collectively, this study may
      provide insight into the mechanisms by which microenvironmental niche signals
      regulate NSCs.

PMID- 17211449
TI  - Niche regulation of corneal epithelial stem cells at the limbus.
AB  - Among all adult somatic stem cells, those of the corneal epithelium are unique in
      their exclusive location in a defined limbal structure termed Palisades of Vogt.
      As a result, surgical engraftment of limbal epithelial stem cells with or without
      ex vivo expansion has long been practiced to restore sights in patients inflicted
      with limbal stem cell deficiency. Nevertheless, compared to other stem cell
      examples, relatively little is known about the limbal niche, which is believed to
      play a pivotal role in regulating self-renewal and fate decision of limbal
      epithelial stem cells. This review summarizes relevant literature and formulates
      several key questions to guide future research into better understanding of the
      pathogenesis of limbal stem cell deficiency and further improvement of the tissue
      engineering of the corneal epithelium by focusing on the limbal niche.

PMID- 17211452
TI  - Differences between the abilities of tegaserod and motilin receptor agonists to
      stimulate gastric motility in vitro.
AB  - BACKGROUND AND PURPOSE: Motilin or 5-HT4 receptor agonists stimulate
      gastrointestinal motility. Differences in activity are suggested but direct
      comparisons are few. A method was devised to directly compare the gastric
      prokinetic activities of motilin, the motilin receptor agonist, erythromycin, and
      the 5-HT4 receptor agonist, tegaserod. EXPERIMENTAL APPROACH: Gastric prokinetic
      like activity was assessed by measuring the ability to facilitate cholinergically
      mediated contractions evoked by electrical field stimulation (EFS) in rabbit
      isolated stomach. Comparisons were made between potency, maximal activity and
      duration of responses. KEY RESULTS: Rabbit motilin (r.motilin) 0.003-0.3 microM,
      [Nle13]motilin 0.003-0.3 microM, erythromycin 0.3-10 microM and tegaserod 0.1-10
      microM caused concentration - dependent potentiation of EFS-evoked contractions.
      The potency ranking was r.motilin = [Nle13]motilin > tegaserod > erythromycin.
      The Emax ranking was r.motilin = [Nle13]motilin = erythromycin > tegaserod.
      Responses to r.motilin and [Nle13]motilin faded rapidly (t1/2 9 and 11 min,
      respectively) whereas those to erythromycin and tegaserod were maintained longer
      (t1/2 24 and 28 min). The difference did not appear to be due to peptide
      degradation. A second application of [Nle13]motilin was excitatory after 60 min
      contact and fade of the initial response (responses to 0.03 and 0.1 microM
      [Nle13]motilin were not different from those caused by the first application).
      CONCLUSIONS AND IMPLICATIONS: Prokinetic-like activities of the 5-HT4 agonist
      tegaserod and the motilin receptor agonists were compared by measuring changes in
      cholinergically-mediated contractions. This novel approach highlighted important
      differences between classes (greater Emax of motilin, compared with tegaserod)
      and for the first time, within each class (short t1/2 for motilin, compared with
      erythromycin).

PMID- 17211453
TI  - Differential effects of nitric oxide synthase inhibitors on endothelium-dependent
      and nitrergic nerve-mediated vasodilatation in the bovine ciliary artery.
AB  - BACKGROUND AND PURPOSE: We have previously demonstrated that L-NMMA (NG
      monomethyl-L-arginine) selectively inhibits vasodilatation produced by
      endothelium-derived nitric oxide but not nitrergic nerves in the bovine penile
      artery. The present study investigated whether L-NMMA had a similar selective
      action in the bovine ciliary artery. We also investigated whether two recently
      introduced inhibitors of neuronal nitric oxide synthase (nNOS), AAAN (N-(4S)-4
      amino-5-[aminoethyl]aminopentyl-N'-nitroguanidine) and L-NPA (NG-propyl-L
      arginine), produced selective blockade of vasodilatation induced by nitrergic
      nerves but not endothelium-derived nitric oxide. EXPERIMENTAL APPROACH: Rings of
      bovine ciliary artery were suspended in a wire myograph for tension recording.
      Neurogenic (nitrergic) vasodilatation was elicited by electrical field
      stimulation, and endothelium-dependent, nitric oxide-mediated dilatation was
      evoked using bradykinin. KEY RESULTS: L-NMMA inhibited vasodilatation induced by
      endothelium-derived nitric oxide but not the nitrergic nerves. In fact, L-NMMA,
      acted like L-arginine in protecting nitrergic vasodilatation against inhibition
      by L-NAME (NG-nitro-L-arginine methyl ester). AAAN had no effect on
      vasodilatation induced by either nitrergic nerves or endothelium-derived nitric
      oxide, but L-NPA inhibited both with equal potency. CONCLUSIONS AND IMPLICATIONS:
      In the bovine ciliary artery, L-NMMA acts as a selective inhibitor of the
      vasodilatation induced via endothelial NOS, without affecting that operating via
      nNOS. Furthermore, the putative nNOS inhibitors, AAAN and L-NPA failed to produce
      the expected selective inhibition of nitrergic vasodilatation in this artery.

PMID- 17211454
TI  - Urotensin-II induces ear flushing in rats.
AB  - BACKGROUND AND PURPOSE: While investigating the effects of systemic urotensin II
      (U-II), a potent vasoactive peptide acting at the UT receptor, we observed ear
      pinna flushing after systemic administration to conscious rats. In the present
      study, U-II-induced ear flushing was quantified in terms of ear pinna temperature
      change and potential mechanisms were explored. EXPERIMENTAL APPROACH: U-II
      induced ear flushing was quantified by measuring lateral ear pinna temperature
      changes and compared to that of calcitonin gene-related peptide (CGRP), a known
      cutaneous vasodilator. Further, the effects of a variety of pharmacological
      agents on U-II-induced ear flushing were explored. KEY RESULTS: Subcutaneous
      injection of U-II (9 microg kg(-1))produced localized ear pinna flushing with an
      onset of approximately 15 min, a duration of approximately 30 min and a maximal
      temperature change of 9 degrees C. In contrast, CGRP caused cutaneous flushing
      within multiple cutaneous beds including the ear pinna with a shorter onset and
      greater duration than U-II. A potent UT receptor antagonist, urantide, blocked U
      II-induced ear flushing but did not affect CGRP-induced ear flushing.
      Pretreatment with indomethacin or L-Nomega-nitroarginine methylester (L-NAME)
      abolished U-II-induced ear flushing. Mecamylamine or propranolol did not affect
      this response to U-II. Direct intracerebroventricular injection studies suggested
      that the ear flushing response to U-II was not mediated directly by the CNS.
      CONCLUSION AND IMPLICATIONS: Our results suggest that U-II-induced ear flushing
      and temperature increase is mediated by peripheral activation of the UT receptor
      and involves prostaglandin- and nitric oxide-mediated vasodilation of small
      capillary beds in the rat ear pinna.

PMID- 17211456
TI  - Increase in exhaled nitric oxide and protective role of the nitric oxide system
      in experimental pulmonary embolism.
AB  - BACKGROUND AND PURPOSE: Pulmonary embolism (PE) represents a real diagnostic
      challenge. PE is associated with pulmonary hypertension due to pulmonary vascular
      obstruction and vasoconstriction. We recently reported that pulmonary gas
      embolism transiently increases exhaled nitric oxide (FENO), but it is not known
      whether solid emboli may alter FENO, and whether an intact endogenous NO
      synthesis has a beneficial effect in experimental solid pulmonary embolism.
      EXPERIMENTAL APPROACH: We used anaesthetised and ventilated rabbits in these
      experiments. To mimic PE, a single intravenous infusion of homogenized autologous
      skeletal muscle tissue (MPE) was given to rabbits with intact NO production (MPE
      of 60, 15, or 7.5 mg kg(-1); group 1) and to another group (group 2) with
      inhibited NO synthesis (L-NAME 30 mg kg(-1); MPE of 7.5, 15 or 30 mg kg(-1)). KEY
      RESULTS: In group 1, after MPE, FENO increased rapidly and dose-dependently and
      FENO was still significantly elevated after 60 min with the two highest emboli
      doses. All these animals survived more than 60 min after embolization. In group
      2, MPE of 7.5, 15 and 30 mg kg(-1), in combination with NO synthesis inhibition,
      resulted in 67%, 50% and 25% survival at 60 min respectively, representing a
      statistically significant decrease in survival. Cardiovascular and blood-gas
      changes after MPE were intensified by pre-treatment with NO synthesis inhibitor.
      CONCLUSIONS AND IMPLICATIONS: We conclude that solid PE causes a sustained, dose
      dependent increase in FENO, giving FENO a diagnostic potential in PE.
      Furthermore, intact NO production appears critical for tolerance to acute PE.

PMID- 17211455
TI  - Neuromedin U can exert colon-specific, enteric nerve-mediated prokinetic
      activity, via a pathway involving NMU1 receptor activation.
AB  - BACKGROUND AND PURPOSE: The neuromedin U (NMU) receptors, NMU1 and NMU2, are
      expressed in the gut but their functions are unclear. This study explores the
      role of NMU in gastrointestinal motility. EXPERIMENTAL APPROACH: The effects of
      NMU were examined in the forestomach and colon isolated from NMU2R wild-type and
      NMU2R-/- (knockout) mice, looking for changes in muscle tension and in nerve
      mediated responses evoked by electrical field stimulation (EFS), and in models of
      peristalsis in mouse colon and faecal pellet transit in guinea-pig colon. KEY
      RESULTS: In the mouse forestomach, NMU (1 nM-10 microM) concentration-dependently
      induced muscle contraction, in the presence of tetrodotoxin and atropine, in
      preparations from both wild-type and NMU2R-/- mice (pEC50: 7.9, 7.6, Emax: 0.26,
      0.20g tension, respectively, n=8 each concentration). The same concentrations of
      NMU had no consistent effects on the responses to EFS (n=8). In the mouse colon,
      NMU (0.1 nM-1 microM) had no significant effect on baseline muscle tension (n=8),
      but concentration-dependently potentiated EFS-evoked contractions in preparations
      from both wild-type and NMU2R-/- mice, pEC50: 8.1, 7.8, Emax: 24%, 21%,
      respectively, n=6-11. NMU (0.01 nM-0.1 microM, n=5-7) concentration-dependently
      decreased the interval between waves of peristalsis in the mouse colon (pEC50:
      8.8) and increased the rate at which a faecal pellet moved along the guinea-pig
      colon. CONCLUSIONS AND IMPLICATIONS: These results demonstrate that NMU exerts
      colon-specific, nerve-mediated, prokinetic activity, via a pathway involving
      activation of NMU1 receptors. This suggests that this receptor may represent a
      molecular target for the treatment of intestinal motility disorders.

PMID- 17211457
TI  - Increase in weight induced by muraglitazar, a dual PPARalpha/gamma agonist, in
      db/db mice: adipogenesis/or oedema?
AB  - BACKGROUND AND PURPOSE: Muraglitazar, a dual PPARalpha/gamma agonist, caused a
      robust increase in body weight in db/db mice. The purpose of the study was to see
      if this increase in weight was due to oedema and/or adipogenesis. EXPERIMENTAL
      APPROACH: The affinity of muraglitazar at PPARalpha/gamma receptors was
      characterized using transactivation assays. Pre-adipocyte differentiation,
      expression of genes for adipogenesis (aP2), fatty acid oxidation (ACO) and sodium
      reabsorption (ENaCgamma and Na+, K+-ATPase); haemodilution parameters and serum
      electrolytes were measured to delineate the role of muraglitazar in causing
      weight gain vis a vis rosiglitazone. KEY RESULTS: Treatment with muraglitazar (10
      mg kg(-1)) for 14 days significantly reduced plasma glucose and triglycerides.
      Reduction in plasma glucose was significantly greater than after similar
      treatment with rosiglitazone (10 mg kg(-1)). A marked increase in weight was also
      observed with muraglitazar that was significantly greater than with
      rosiglitazone. Muraglitazar increased aP2 mRNA and caused adipocyte
      differentiation in 3T3-L1 cells similar to rosiglitazone. It also caused a marked
      increase in ACO mRNA in the liver of the treated mice. Expression of mRNA for
      ENaCgamma and Na+, K+-ATPase in kidneys was up-regulated after either treatment.
      Increased serum electrolytes and decreased RBC count, haemoglobin and haematocrit
      were observed with both muraglitazar and rosiglitazone. CONCLUSIONS AND
      IMPLICATIONS: Although muraglitazar has a better glucose lowering profile, it
      also has a greater potential for weight gain than rosiglitazone. In conclusion,
      muraglitazar causes both robust adipogenesis and oedema in a 14-day treatment of
      db/db mice as observed in humans.

PMID- 17211458
TI  - Cellular mechanisms underlying the pharmacological induction of phosphenes.
AB  - Visual sensations evoked by stimuli other than luminance changes are called
      phosphenes. Phosphenes may be an early symptom in a variety of diseases of the
      retina or of the visual pathways, but healthy individuals may perceive them as
      well. Phosphene-like phenomena are perhaps the most common side effect reported
      in clinical pharmacology. Ivabradine, a novel anti-anginal drug that reduces
      heart-rate by inhibiting the hyperpolarization activated current expressed in
      cardiac sinoatrial node cells (I(f)) induces phosphenes in some patients. One
      hypothesis is that ivabradine interacts with the visual system by inhibiting
      hyperpolarization-activated current in retinal cells (Ih). An Ih current with
      properties similar to cardiac I(f) has been reported in retinal neurones. Under
      normal circumstances most of the random fluctuations generated within the retinal
      circuits do not reach the level of conscious perception because they are filtered
      out. Presumably, filtering occurs mostly within the retina and one serious
      candidate for this action is the ability of Ih to act as a negative-feedback
      mechanism. Ih activation in the membrane of visual cells causes dampening of
      responses to slow noisy inputs thus tuning the visual system to perceptually more
      relevant signals of higher frequency. Ih inhibition, by altering at the retinal
      synapses the filtering of signals generated by thermal breakdown of rhodopsin or
      other fluctuations, is expected to increase the probability of phosphene
      occurrence. It is the purpose of the present paper to outline and discuss the
      features of the visual system and the pharmacological conditions relevant to
      phosphene perception.

PMID- 17211459
TI  - Modulation of P2X7 receptor functions by polymyxin B: crucial role of the
      hydrophobic tail of the antibiotic molecule.
AB  - BACKGROUND AND PURPOSE: P2X7 is a membrane receptor for extracellular ATP which
      is highly expressed in dendritic cells, macrophages and microglia where it
      mediates pro-inflammatory responses. The antibiotic polymyxin B, which binds to
      and neutralizes the toxic residue of bacterial lipopolysaccharide, greatly
      amplifies cellular responses mediated by the P2X7 receptor. However, the
      molecular mechanism involved is so far unknown. EXPERIMENTAL APPROACH: We
      investigated the effects of polymyxin B and polymyxin B nonapeptide (PMBN) which
      is the deacylated amino derivative of polymyxin B lacking the N-terminal fatty
      amino acid 6-methylheptanoic/octanoic-Dab residue, in human macrophages and
      HEK293 cells stably expressing the human P2X7 receptor (HEK293-hP2X7).
      Differences between the two antibiotics were assessed by monitoring the
      following: nucleotide-induced cytoplasmic free Ca2+ concentration changes, plasma
      membrane permeability changes, lactate dehydrogenase activity, cell morphology
      changes. Western blot and microscopic analyses of P2X7GFP-expressing cells were
      also performed. KEY RESULTS: In contrast to polymyxin B, the polymyxin B
      nonapeptide was unable to potentiate: a) the ATP-induced Ca2+ increase, b) pore
      formation and consequently ATP-mediated plasma membrane permeabilization; c) ATP
      dependent cytotoxicity. Moreover, in contrast to polymyxin B, polymyxin B
      nonapeptide did not affect aggregation of the P2X7 receptor subunits and it did
      not potentiate P2X7-dependent cell fusion. CONCLUSIONS AND IMPLICATIONS: The
      effects of polymyxin B depended on the presence of its N-terminal fatty amino
      acid 6-methylheptanoic/octanoic-Dab residue as deletion of this residue abolished
      polymyxin B-dependent modulation of ATP-triggered responses. These findings are
      important in the search for allosteric modulators of the P2X7 receptor.

PMID- 17211461
TI  - Ultra-early MRI showing no abnormality in a fall victim presenting with
      tetraparesis.
AB  - STUDY DESIGN: Case report. SETTING: Department of Neurosurgery, Sapporo Azabu
      Neurosurgical Hospital and Department of Neurosurgery, Hokkaido University
      Graduate School of Medicine, Sapporo, Japan. CASE REPORT: A patient presented to
      us with complete C4 tetraplegia after a 3-m fall. MRI performed 120 min after his
      fall showed spinal canal stenosis due to disk protrusion at the C3/4 level
      without spinal cord signal changes on T1- and T2-weighted images. He underwent
      laminoplasty between C2 and C6. Intraoperative ultrasound, performed 6 h after
      his fall, disclosed a hyperechoic lesion at the C3/4 level of the cervical cord;
      postoperative T2-weighted MRI, obtained at 8 h after his fall, showed high
      intensity at the same level. CONCLUSION: In patients with cerebral infarction,
      approximately 6 h between the insult and the acquisition of T2-weighted MRI are
      required to detect signal changes. We postulate that the time course on MRI scans
      obtained immediately after spinal cord injury is similar in patients with spinal
      cord injury and cerebral infarction and suggest that the absence of spinal cord
      abnormalities in the ultra-early post-injury stage is not always predictive of a
      good prognosis.

PMID- 17211460
TI  - Danofloxacin-mesylate is a substrate for ATP-dependent efflux transporters.
AB  - BACKGROUND AND PURPOSE: Next to its broad antimicrobial spectrum, the therapeutic
      advantages of the fluoroquinolone antimicrobial drug Danofloxacin-Mesylate (DM)
      are attributed to its rapid distribution to the major target tissues such as
      lungs, intestines and the mammary gland in animals. Previous analyses revealed
      that effective drug concentrations are achieved also in luminal compartments of
      these organs, suggesting that active transport proteins facilitate excretion into
      the luminal space. Members of the ATP-Binding Cassette (ABC) superfamily,
      including P-gp, BCRP and MRP2 are known to be expressed in many tissue barriers
      and in cell-membranes facing luminal compartments. Hence we hypothesized that DM
      is a substrate for one of these efflux-transporters. EXPERIMENTAL APPROACH:
      Confluent monolayers of Caco-2 cells, grown on microporous membranes in two
      chamber devices were used. DM concentrations were measured by fluorimetric assay
      after HPLC of the culture media. KEY RESULTS: DM transport across Caco-2 cells
      was asymmetric, with a rate of secretion exceeding that of absorption. The P-gp
      inhibitors PSC833 and GF120918 and the MRP-inhibitor MK571 partially decreased
      the secretion of DM and increased its absorption rate. The BCRP inhibitor, Ko143,
      decreased secretion only at a concentration of 1 microM. When DM was applied
      together with ciprofloxacin, secretion as well as absorption of DM decreased.
      CONCLUSIONS AND IMPLICATIONS: DM is a substrate for the efflux transporters P-gp
      and MRP2, whereas the specific role of BCRP in DM transport needs further
      evaluation. These findings provide a mechanistic basis for the understanding of
      the pharmacokinetics of DM in healthy and diseased individuals.

PMID- 17211462
TI  - Observation of locomotor functional recovery in adult complete spinal rats with
      BWSTT using semiquantitative and qualitative methods.
AB  - STUDY DESIGN: Experimental rat model of spinal cord transection . SETTING: China
      rehabilitation research center. OBJECTIVE: To investigate locomotor functional
      recovery in spinal rats with BWSTT using semiquantitative and qualitative
      methods. METHODS: Five-day postoperative (dpo), adult female complete spinal rats
      (at T(8) level) received 40 days of body weight-supported treadmill training
      (BWSTT). Signs of functional recovery were examined with average combined scores
      (ACOS) and Basso Beattie and Bresnahan (BBB) scales at different time points.
      RESULTS: At 1-dpo, none of the spinal rats exhibited hindlimb movements. The
      spinal rats displayed functional progress with time, but the rare could recover
      to full weight-bearing hindlimb at 45-dpo. BBB and ACOS scores in the BWSTT group
      obtained better scores than those in the spinal cord injury (SCI) group at 30-
      and 45-dpo. Furthermore, all BBB and ACOS scores of spinal rats reached
      statistical significance between 7- and 30-dpo, and between 15- and 30-dpo.
      However, only ACOS but not BBB scores in the SCI and BWSTT groups showed
      statistics differences between 15- and 45-dpo, and between 30- and 45-dpo. The
      Spearman correlation coefficients of BBB and ACOS scores were 0.913 and 0.972 for
      the SCI and BWSTT groups, respectively. CONCLUSIONS: The results confirmed the
      existence of partial spontaneous hindlimb functional recovery in adult
      chronically spinal cord-transected rats, and that BWSTT can improve motor
      performance. In addition, our study suggests that qualitative and semiquantiative
      methods are strongly correlated with locomotor recovery in spinal rats, and the
      latter may be more sensitive in reflecting minor variance at different time
      points.

PMID- 17211463
TI  - Long-term follow-up study of intraurethral stents in spinal cord injured patients
      with detrusor-sphincter dyssynergia.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVES: To assess in the long-term
      clinical and urodynamic results of intraurethral stents in a group of patients
      with spinal cord injury. SETTING: Spinal Cord Injury Unit, Juan Canalejo
      Hospital, A Coruna, Spain. METHODS: Forty-seven consecutive male patients were
      studied from 1993 to 2002. All of them suffered from hyperreflexia with detrusor
      sphincter dyssynergia (DSD) owing to spinal cord injury, and were treated by
      means of the placement of an intraurethral stent at the external sphincter.
      RESULTS: After surgery, significant decreases in all the parameters studied were
      observed. The number of patients with symptoms of urinary tract infection
      decreased by 25% (P<0.031). Post-void residual urine volume experienced an
      average decrease of 224.3 cm(3) (P=0.001). Episodes of dysreflexia decreased from
      35.1 to 16.2% (P=0.039). The urodynamic study showed an average reduction of
      44.36 cm H(2)O in the maximum detrusor pressure (P<0.0001). Complications in the
      upper urinary tract descended from 46.8 to 23.4% after placing the stent
      (P=0.013). The most frequent stent complication was displacement, followed by
      stenosis, lithiasis and intraprosthetic calcification. In all, 8.5% required the
      stent removal. CONCLUSIONS: Intraurethral stent is a good choice for the long
      term management of DSD in spinal cord-injured patients, even in those who had
      been previously submitted to prior sphincterotomy. It has the advantage of being
      a potentially reversible procedure, so patients prefer it to more invasive
      therapies such as sphincterotomy.

PMID- 17211465
TI  - C-reactive protein as a predictor of prognosis following curative resection for
      colorectal liver metastases.
AB  - There is increasing evidence that systemic inflammatory response has a positive
      correlation with a poorer outcome in patients undergoing resection for solid
      tumours. The aim of this study was to analyse the impact of an elevated C
      reactive protein (CRP), an outcome following curative resection for colorectal
      liver metastases. One hundred and seventy patients who underwent curative
      resection for colorectal liver metastases were included in the study. Laboratory
      measurements of haemoglobin, white cell, platelets, albumin and CRP were taken on
      the day before surgery. Elevated CRP (>10 mg l(-1)) was present in 54 (31.8%)
      patients. The median survival of patients with an elevated CRP was 19 months (95%
      CI 7.5-31.2 months) compared to 42.8 months (95% CI 33.2-52.5 months) for those
      with a normal CRP, P=0.004. Similarly, when assessing disease-free survival,
      patients with an elevated CRP had poorer disease-free survival (median of 11.8
      months (95% CI 6.4-17.3) compared to median of 15.1 months (95% CI 11.1-19.1)),
      P=0.043. The result of the study showed that an elevated preoperative CRP is a
      predictor of poor outcome in patients undergoing curative resection for
      colorectal liver metastases.

PMID- 17211466
TI  - A physical analysis of the Y chromosome shows no additional deletions, other than
      Gr/Gr, associated with testicular germ cell tumour.
AB  - Testicular germ cell tumour (TGCT) is the most common malignancy in men aged 15
      45 years. A small deletion on the Y chromosome known as 'gr/gr' was shown to be
      associated with a two-fold increased risk of TGCT, increasing to three-fold in
      cases with a family history of TGCT. Additional deletions of the Y chromosome,
      known as AZFa, AZFb and AZFc, are described in patients with infertility;
      however, complete deletions of these regions have not been identified in TGCT
      patients. We screened the Y chromosome in a series of TGCT cases to evaluate if
      additional deletions of Y were implicated in TGCT susceptibility. Single copy Y
      chromosome STS markers with an average inter-marker spacing of 128 kb were
      examined in constitutional DNA of 271 index TGCT patients. Three markers showed
      evidence of deletions, sY1291, indicative of 'gr/gr' (eight out of 271; 2.9%), Y
      DAZ3 contained within 'gr/gr' (21 out of 271; 7.7%) and a single deletion of the
      marker G66152 was identified in one TGCT case. No other markers demonstrated
      deletions. While several regions of the Y chromosome are known to be deleted and
      associated with infertility, our study provides no evidence to suggest regions of
      Y deletion, other than 'gr/gr', are associated with susceptibility to TGCT in UK
      patients.

PMID- 17211467
TI  - Potentiation of antitumour activity of docetaxel by combination with trastuzumab
      in a human prostate cancer xenograft model and underlying mechanisms.
AB  - Antitumour activity of docetaxel (Taxotere) in hormone-dependent (HD) and hormone
      independent (HID) prostate cancer PAC120 xenograft model was previously reported,
      and its level was associated with HER2 protein expression. In the present study,
      we evaluate the antitumour effects of docetaxel combined with trastuzumab
      (Herceptin), an anti-HER2 antibody. Although trastuzumab alone had no effect on
      tumour growth, it potentiated the antitumour activity of docetaxel in HD tumours
      and more strongly in HID variants. Using the HID28 variant, we show that
      docetaxel treatment of tumour-bearing mice induces an increased HER2 mRNA
      expression of the tyrosine kinase receptor of 25-fold 24 h after docetaxel
      treatment, while HER2 protein and p-AKT decreased. This was followed by an
      increase of HER2 protein 3 days (two-fold) after docetaxel treatment and by a
      strong HER2 release in the serum of treated mice; expression of phospho-ERK, p27,
      BCL2 and HSP70 concomitantly increased. Similar molecular alterations were
      induced by docetaxel plus trastuzumab combination, except for that there was a
      transient and complete disappearance of AR and HSP90 proteins 24 h after
      treatment. We show that in addition to its known effects on tubulin and mitotic
      spindles, docetaxel induces complex signalisation pathway mechanisms in surviving
      cells, including HER2, which can be pharmacologically targeted. This study
      suggests that the docetaxel/trastuzumab combination may prove an effective
      therapeutic approach for HER2-expressing hormone-refractory prostate cancer.

PMID- 17211468
TI  - Tissue factor expression as a possible determinant of thromboembolism in ovarian
      cancer.
AB  - Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the
      risk of venous thromboembolism (VTE). However, the mechanisms remain unclear.
      Tissue factor (TF) supposedly represents a major factor in the procoagulant
      activities of cancer cells. The present study examined the involvement of TF
      expression in VTE for patients with ovarian cancer. Subjects comprised 32
      consecutive patients (mean age 49.8 years) with histologically confirmed ovarian
      cancer. Presence of VTE was examined using a combination of clinical features, D
      dimer levels and venous ultrasonography. Immunohistochemical analysis was used to
      evaluate TF expression into 4 degrees. Venous thromboembolism was identified in
      10 of the 32 patients (31%), including five of the 11 patients with clear cell
      carcinoma. Tissue factor expression was detected in cancer tissues from 24
      patients and displayed significant correlations with VTE development (P=0.0003),
      D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate
      analysis identified TF expression as an independent predictive factor of VTE
      development (P<0.05). Tissue factor (TF) expression is a possible determinant of
      VTE development in ovarian cancer. In particular, clear cell carcinoma may
      produce excessive levels of TF and is more likely to develop VTE.

PMID- 17211469
TI  - HIF and fumarate hydratase in renal cancer.
AB  - Hereditary leiomyomatosis and renal cell cancer is a recently described
      hereditary cancer syndrome in which affected individuals are predisposed to the
      development of leiomyomas of the skin and uterus. In addition, this clinical
      entity also can result in the development of biologically aggressive kidney
      cancer. Affected individuals harbour a germline mutation of the fumarate
      hydratase (FH) gene, which encodes an enzyme that catalyses conversion of
      fumarate to malate in the Kreb's cycle. Thus far, proposed mechanisms for
      carcinogeneis associated with this syndrome include aberrant apoptosis, oxidative
      stress, and pseudohypoxic drive. At this time, the majority of accumulating data
      support a role for pseudohypoxic drive in tumour development. The link between FH
      mutation and pseudohypoxic drive may reside in the biochemical alterations
      resulting from diminished/absent FH activity. These biochemical derangements may
      interfere with oxygen homeostasis and result in a cellular environment conducive
      to tumour formation.

PMID- 17211470
TI  - Immunostaining of thymidylate synthase and p53 for predicting chemoresistance to
      S-1/cisplatin in gastric cancer.
AB  - High expression of thymidylate synthase (TS) and inactivation of p53 are
      allegedly associated with chemoresistance. The authors evaluated TS and p53
      expression in gastric cancer treated with neoadjuvant S-1/cisplatin chemotherapy.
      Paraffin sections of pretreatment biopsy and surgical specimens from 41 gastric
      cancers were immunostained for TS and p53 protein after appropriate antigen
      retrieval. Fifty-one cases without neoadjuvant chemotherapy were also studied. In
      the pretreatment biopsies, high expression of TS was seen in 8% of the histologic
      responders, in 28% of the nonresponders and in 31% of the controls. High
      expression of p53 was observed in 56% of the nonresponders, but in 8% of the
      responders and in 29% of the controls (P<0.01 and P<0.05, respectively). The TS-
      and/or p53-high phenotype was seen in 76% of the nonresponders and in 54% of the
      controls, but in 8% of the responders (P<0.0001 and P<0.005, respectively). The
      data of the surgical specimens were consistent with those of the pretreatment
      biopsies. These results suggest that immunostaining for TS and p53 protein is
      useful for pretreatment selection of gastric cancer patients unresponsive to S
      1/cisplatin chemotherapy.

PMID- 17211472
TI  - Proteomic identification of secreted proteins as surrogate markers for signal
      transduction inhibitor activity.
AB  - Epidermal growth factor receptor is a potential target for cancer treatment and
      new small-molecule tyrosine kinase inhibitor drugs have been designed to inhibit
      its activity. In this work we identify potential surrogate markers of drug
      activity using a proteomic analysis. Two-dimensional electrophoresis was
      optimised to compare expression patterns of proteins secreted from the cancer
      cell lines A431 and A549 treated with Gefitinib (Iressa) vs untreated or vehicle
      only-treated samples. Upregulated or downregulated proteins were detected using
      Phoretix 2D image analysis software. Several proteins were then identified using
      matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass
      spectrometry. In one case, upregulation of Protein Disulphide Isomerase in
      response to Gefitinib was confirmed by Western blot analysis, and the response
      was shown to be concentration dependent. The identification of surrogate markers
      may be of use for the evaluation of new drugs, in preclinical models, in clinical
      trials and in the therapy of individual patients to give optimal biological drug
      doses.

PMID- 17211471
TI  - Overexpression of LASP-1 mediates migration and proliferation of human ovarian
      cancer cells and influences zyxin localisation.
AB  - LIM and SH3 protein 1 (LASP-1), initially identified from human breast cancer, is
      a specific focal adhesion protein involved in cell proliferation and migration.
      In the present work, we analysed the effect of LASP-1 on biology and function of
      human ovarian cancer cell line SKOV-3 using small interfering RNA technique
      (siRNA). Transfection with LASP-1-specific siRNA resulted in a reduced protein
      level of LASP-1 in SKOV-3 cells. The siRNA-treated cells were arrested in G(2)/M
      phase of the cell cycle and proliferation of the tumour cells was suppressed by
      60-90% corresponding to around 70% of the cells being transfected successfully as
      seen by immunofluorescence. Moreover, transfected tumour cells showed a 40%
      reduced migration. LASP-1 silencing is accompanied by a reduced binding of the
      LASP-1-binding partner zyxin to focal contacts without changes in actin stress
      fibre and microtubule organisation or focal adhesion morphology as observed by
      immunofluorescence. In contrast, silencing of zyxin is not influencing cell
      migration and had neither influence on LASP-1 expression nor actin cytoskeleton
      and focal contact morphology suggesting that LASP-1 is necessary and sufficient
      for recruiting zyxin to focal contacts. The data provide evidence for an
      essential role of LASP-1 in tumour cell growth and migration, possibly through
      influencing zyxin localization.

PMID- 17211473
TI  - Evaluation of the cancer chemopreventive efficacy of rice bran in genetic mouse
      models of breast, prostate and intestinal carcinogenesis.
AB  - Brown rice is a staple dietary constituent in Asia, whereas rice consumed in the
      Western world is generally white, obtained from brown rice by removal of the
      bran. We tested the hypothesis that rice bran interferes with development of
      tumours in TAg, TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) or
      Apc(Min) mice, genetic models of mammary, prostate and intestinal carcinogenesis,
      respectively. Mice received rice bran (30%) in AIN-93G diet throughout their post
      weaning lifespan. In TAg and TRAMP mice, rice bran did not affect carcinoma
      development. In TRAMP or wild-type C57Bl6/J mice, dietary rice bran increased
      kidney weight by 18 and 20%, respectively. Consumption of rice bran reduced
      numbers of intestinal adenomas in Apc(Min) mice by 51% (P<0.01), compared to mice
      on control diet. In parallel, dietary rice bran decreased intestinal haemorrhage
      in these mice, as reflected by increased haematocrit. At 10% in the diet, rice
      bran did not significantly retard Apc(Min) adenoma development. Likewise, low
      fibre rice bran (30% in the diet) did not affect intestinal carcinogenesis,
      suggesting that the fibrous constituents of the bran mediate chemopreventive
      efficacy. The results suggest that rice bran might be beneficially evaluated as a
      putative chemopreventive intervention in humans with intestinal polyps.

PMID- 17211474
TI  - Role of the progesterone receptor for paclitaxel resistance in primary breast
      cancer.
AB  - Paclitaxel plays an important role in the treatment of primary breast cancer.
      However, a substantial proportion of patients treated with paclitaxel does not
      appear to derive any benefit from this therapy. We performed a prospective study
      using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of
      primary tumour cells to paclitaxel was determined in a clinically relevant range
      of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay.
      Chemosensitivity data were used to study a possible association with
      immunohistochemically determined oestrogen and progesterone receptor (ER and PR)
      status, as well as histopathological parameters. Progesterone receptor (PR) mRNA
      expression was also determined by quantitative RT-PCR. We observed a clear
      association of the PR status with chemosensitivity to paclitaxel. Higher levels
      of immunohistochemically detected PR expression correlated with decreased
      chemosensitivity (P=0.008). Similarly, high levels of PR mRNA expression were
      associated with decreased paclitaxel chemosensitivity (P=0.007). Cells from
      carcinomas with T-stages 3 and 4 were less sensitive compared to stages 1 and 2
      (P=0.013). Multiple regression analysis identified PR receptor status and T-stage
      as independent predictors of paclitaxel chemosensitivity, whereas the ER, N
      stage, grading and age were not influential. In conclusion, in vitro sensitivity
      to paclitaxel was higher for PR-negative compared with PR-positive breast
      carcinoma cells. Thus, PR status should be considered as a possible factor of
      influence when designing new trials and chemotherapy protocols.

PMID- 17211475
TI  - The decatenation checkpoint.
AB  - The decatenation checkpoint delays entry into mitosis until the chromosomes have
      been disentangled. Deficiency in or bypass of the decatenation checkpoint can
      cause chromosome breakage and nondisjunction during mitosis, which results in
      aneuploidy and chromosome rearrangements in the daughter cells. A deficiency in
      the decatenation checkpoint has been reported in lung and bladder cancer cell
      lines and may contribute to the accumulation of chromosome aberrations that
      commonly occur during tumour progression. A checkpoint deficiency has also been
      documented in cultured stem and progenitor cells, and cancer stem cells are
      likely to be derived from stem and progenitor cells that lack an effective
      decatenation checkpoint. An inefficient decatenation checkpoint is likely to be a
      source of the chromosome aberrations that are common features of most tumours,
      but an inefficient decatenation checkpoint in cancer stem cells could also
      provide a potential target for chemotherapy.

PMID- 17211476
TI  - Association of FOBT-assessed faecal Hb content with colonic lesions detected in
      the Florence screening programme.
AB  - We assessed the correlation between quantitative results of immunological faecal
      occult blood testing (I-FOBT) and colonic lesions (191 colorectal cancers, 890
      adenomas) detected at colonoscopy in 2597 FOBT+ (cutoff 100 ng ml(-1) Hb)
      subjects. At univariate analysis, a higher average faecal Hb content was
      significantly associated with male gender (P=0.003), age (P=0.02), and
      colonoscopy findings (P=0.000). Among adenomas, higher faecal Hb content was
      significantly associated with size (P=0.0000), presence of severe dysplasia
      (P=0.0001), presence of villous component (P=0.0002), and location in the left
      colon (P=0.003). At multivariate analysis adjusting for potential confounders,
      age (P=0.03), size (P=0.0000), and location in the left colon (P=0.0005) were
      confirmed as having an independent association with higher faecal Hb content.
      Immunological FOBT is confirmed to be a specific screening test to detect cancer
      and adenoma, with a low positivity rate (3.7%) and a high positive predictive
      value (41.5%). Faecal Hb content is significantly higher for those lesions
      (cancer and high-risk adenomas) screening is aimed at detecting.

PMID- 17211477
TI  - Expression of Twist increases the risk for recurrence and for poor survival in
      epithelial ovarian carcinoma patients.
AB  - Twist is a transcription factor that regulates the expression of tumour
      suppressors such as E-cadherin. We examined the distribution and expression of
      Twist in human epithelial ovarian carcinoma (EOC) to examine its clinical
      significance. Paraffin sections from EOC tissues (n=82) were immunostained with
      Twist antibody, and the staining intensity was evaluated. The clinicopathological
      factors examined were age, International Federation of Gynecology and Obstetrics
      staging, histological type, tumour grade, preoperative value of CA125, peritoneal
      cytology, volume of ascites and residual tumour after cytoreductive surgery.
      Overall survival (OS) and progression-free survival (PFS) were evaluated using
      the Kaplan-Meier method, and multivariate analysis was performed using the Cox
      proportional hazard analysis. Of the 82 carcinomas, 49 (59.8%) cases were
      negative for Twist immunoexpression, and 33 (40.2%) were positive
      immunoexpression. When categorized into negative vs positive expression, Twist
      was not associated with any of the clinicopathological parameters examined.
      However, positive Twist expression significantly predicted poorer OS and PFS when
      compared with negative expression (P<0.0001). In the multivariate analyses,
      positive Twist expression was the only independent prognostic factor for survival
      in this study (P<0.0001). Positive Twist expression seems to be a useful marker
      in patients with EOC likely to have an unfavourable clinical outcome.

PMID- 17211478
TI  - ASPP: a new family of oncogenes and tumour suppressor genes.
AB  - The apoptosis stimulating proteins of p53 (ASPP) family consists of three
      members, ASPP1, ASPP2 and iASPP. They bind to proteins that are key players in
      controlling apoptosis (p53, Bcl-2 and RelA/p65) and cell growth (APCL, PP1). So
      far, the best-known function of the ASPP family members is their ability to
      regulate the apoptotic function of p53 and its family members, p63 and p73.
      Biochemical and genetic evidence has shown that ASPP1 and ASPP2 activate, whereas
      iASPP inhibits, the apoptotic but not the cell-cycle arrest function of p53. The
      p53 tumour suppressor gene, one of the most frequently mutated genes in human
      cancer, is capable of suppressing tumour growth through its ability to induce
      apoptosis or cell-cycle arrest. Thus, the ASPP family of proteins helps to
      determine how cells choose to die and may therefore be a novel target for cancer
      therapy.

PMID- 17211479
TI  - DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular
      disrupting agents.
AB  - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is now frequently
      used in early clinical trial assessment of antiangiogenic and vascular disrupting
      compounds. Evidence of drug efficacy and dose-dependent response has been
      demonstrated with some angiogenesis inhibitors. This review highlights the
      critical issues that influence T(1)-weighted DCE-MRI data acquisition and
      analysis, identifies important areas for future development and reviews the
      clinical trial findings to date.

PMID- 17211481
TI  - [Intestinal malrotation in the adult: case report and review of literature].
AB  - Intestinal malrotation is a congenital anomaly of intestinal rotation and
      fixation that generally becomes symptomatic at the neonatal period. Uncommonly it
      may occur in older children and adults, requiring imaging studies to suspect and
      confirm the diagnosis. In this case report an intestinal malrotation in a
      previously asymptomatic young adult patient with acute intestinal obstruction is
      described.

PMID- 17211480
TI  - EpCAM (CD326) finding its role in cancer.
AB  - Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the
      first tumour-associated antigens identified, it has never received the same level
      of attention as other target proteins for therapy of cancer. It is also striking
      that ever since its discovery in the late 1970s the actual contribution of EpCAM
      to carcinogenesis remained unexplored until very recently. With a First
      International Symposium on EpCAM Biology and Clinical Application this is now
      changing. Key topics discussed at the meeting were the frequency and level of
      EpCAM expression on various cancers and its prognostic potential, the role of
      EpCAM as an oncogenic signalling molecule for cancer cells, recent progress on
      EpCAM-directed immunotherapeutic approaches in clinical development and the
      interaction of EpCAM with other proteins, which may provide a basis for a
      therapeutic window and repression of its growth-promoting signalling in
      carcinoma. Future research on EpCAM may benefit from a unified nomenclature and
      more frequent exchange among those who have been working on this cancer target
      during the past 30 years and will do so in the future.

PMID- 17211482
TI  - [Esophageal perforation and mediastinitis caused by fishbone ingestion: report of
      3 cases].
AB  - We present 3 consecutive cases of fishbone perforation of the esophagus that
      resulted in acute mediastinitis. All patients were successfully managed with
      drainage and debridement of the mediastinum and pleural cavity. However,
      temporary exclusion with external ligation of the esophagus was also performed in
      one patient, with spontaneous recanalization two weeks later. We discuss the
      possible role of this surgical maneuver in the management of esophageal
      perforation.

PMID- 17211483
TI  - [XX national congress of digestive diseases 2006].

PMID- 17211484
TI  - [Comparative study of D1 and D2 ganglionic dissection in advanced gastric cancer
      at Rebagliati Hospital].
AB  - Gastrectomy with D2 lymphadenectomy is the standard surgical procedure in most
      hospitals in Peru due to the fact that this Japanese surgical technique has
      proven to provide the best results in the world. However, no comparative study of
      the results of D1 and D2 lymphadenectomies has ever been performed in our
      country. This retrospective cohort study compares D2 lymphadenectomy versus D1 in
      surgical treatment of gastric cancer.Between January 2000 and December 2002, 316
      patients underwent surgery at the Rebagliati National Hospital and a total of 100
      patients were randomly selected, 50 of which underwent a D1 lymphadenectomy and
      50 a D2 lymphadenectomy. Mortality rates were 8% for D1 lymphadenectomy and 4%
      for D2, whereas morbidityrates were 24% for D1 and 12% for D2. Survival after 3
      years was 36% for D1 and 56% for D2 thus establishing a statistically significant
      difference (p = 0.04). We recommend gastrectomy with D2 lymphadenectomy as the
      surgical treatment of choice for advanced gastric cancer.

PMID- 17211486
TI  - [Prognostic factors of survival in obstructive and non-obstructive excisable
      colorectal cancer].
AB  - OBJECTIVES: Determining the prognostic factors, clinical and pathological
      characteristics, surgical morbidity and mortality and actuarial survival after
      five (5) years of patients with obstructive and non-obstructive excisable
      colorectal cancer. MATERIAL AND METHODS: Descriptive, correlative, longitudinal
      and observational study at the Belen Hospital in Trujillo of 88 patients with
      excisable colorectal cancer and a histological confirmation of their disease,
      between 1966 and 2000. RESULTS: The mean age of the total series was 62.35 +/-
      14.64 years; the primary tumor (p = 0.001) and regional ganglionic condition (p =
      0.0001) were the factors associated with the five year survival in both groups of
      patients with obstructive and non-obstructive colorectal cancer. Furthermore, the
      size of the tumors and distance metastasis were also prognostic factors
      associated in patients with non-obstructive colorectal cancer. Actuarial survival
      at 60 months of patients with obstructive and non-obstructive colorectal cancer
      who had surgery for curative purposes was 65.5% and 20%, respectively (p =
      0.0135). The actuarial survival rate of patients with obstructive excisable
      colorectal cancer was 9.5% and in patients with non-obstructive colorectal cancer
      it was 35.1% (p = 0.1480). CONCLUSIONS: The primary tumor and regional ganglionic
      condition were prognostic factors in both groups. Furthermore, size of the
      tumors, distance metastasis and clinical stage were also prognostic factors in
      patients with non-obstructive colorectal cancer.

PMID- 17211485
TI  - [Factors associated with strongyloides stercoralis infection in an endemic area
      in Peru].
AB  - In order to determine the epidemiological factors and clinical symptoms
      associated with Strongyloides stercoralis infection, we carried out a descriptive
      study with a control group in the District of Chanchamayo, Province of
      Chanchamayo, Junin, Peru. Group I (n = 50) represented those individuals with
      strongyloidosis and group II (n = 50) were those who tested negative for S.
      stercoralis by parasitological methods. Epidemiological variables significantly
      associated with group I were: bathing in the river 3-4 times per week, consuming
      non-drinking water, defecating in the field; and with group II: drinking boiled
      water, wearing sneakers and living in houses with cement floor. The clinical
      symptoms of epigastric pain, daily abdominal pain, semi liquid feces, liquid
      feces, daily defecation frequency, urticaria and nausea were significantly
      associated with group 1; whereas more solid feces and defecating every other day
      were significantly associated with group II. Among individuals under the age of
      20 there was a higher percentage of malnutrition according to the weight-age
      index in group I (p = 0.045). We conclude that infection by S. stercoralis should
      be suspected in persons from tropical areas who are in frequent contact with
      rivers or streams or live close to watercourses, who have gastroenterological or
      dermatological symptoms or who are malnourished, especially if they are children
      or adolescents.

PMID- 17211488
TI  - [Gastric cancer in Lima].
AB  - Gastric cancer continues to be one of the most common malignant neoplasias in the
      world. Despite the decreasing incidence of this disease in developed countries,
      Eastern Europe and Latin America show the highest incidences. It accounted for
      8.6% of all new cases of cancer in 2002. In Peru it has increased between 1990
      and 1997 amounting to 24.3/100000 in men and 17.6/100000 in women, during the
      last period studied, thus it is considered a high risk area. Mortality: it is
      still the leading cause of death for both sexes, in men it is 19.3/100000 and in
      women 14.2/100000. Incidence is directly proportional to the place of origin in
      Metropolitan Lima, a city of almost 8 million inhabitants, and the districts with
      the highest incidences are Puente Piedra and Lince followed by Villa El Salvador,
      El Augustino, Brena and Rimac among others. These are districts with medium-low
      socioeconomic levels, whereas the lowest incidences are found in districts with
      high socioeconomic levels, such as San Isidro and Miraflores, among others.

PMID- 17211487
TI  - [Isolation of helicobacter pylori in dental plaque in patients with gastritis at
      "Angamos" clinic].
AB  - OBJECTIVE: Detect the presence of (Helicobacter pylori) in dental plaque among
      patients with gastritis diagnosed by biopsy at Angamos Surquillo Hospital.
      MATERIALS AND METHODS:  TYPE OF STUDY: Analytical Observation. POPULATION: 115
      patients scheduled for endoscopy at the Gastroenterological Department of said
      hospital. The methodology employed for the biopsy of the antrum and fundus of the
      stomach was by means of a gastroscope. Once the sample was collected it was
      processed and stained with hematoxilin-eosin for the histological diagnosis of
      gastritis by observation of Helicobacter pylori. Dental plaque samples were
      obtained by scraping the supragingival area and were transported in a
      conservation medium for culture of the bacteria in a selective medium and
      incubated in microaerophilia for 5 to 10 days;suspected colonies were stained and
      compared to a patron strain. Urease and oxidase tests confirmed the diagnosis.
      RESULTS: In total, 66 cases of gastritis associated with H.p. were found by
      biopsy. In 4 of these cases, H.p from dental plaque were also isolated. In
      another group of 49 fases of gastritis not associated with H.p., no H.p. was
      found in the dental plaque of 45 of these cases while H.p. was isolated from
      dental plaque in 4 clases. CONCLUSION: The results show a direct relation between
      the cases of gastritis and the finding of Helicobacter pylori in dental plaque,
      which would indicate a relation between the patients and the bacteria in these
      cases, as they act as a reservoir for said bacteria; as compared with the cases
      in which there is no H.p presence in gastritis without Helicobacter, except in
      four cases. The cases of gastritis with Helicobacter pylori and negative dental
      plaque are not significant, in these cases the bacteria entered with the food.

PMID- 17211489
TI  - [Acute abdominal pain due to splenic infarction in a patient with heterozygous
      sickle cell disease exposed to high altitude].
AB  - Hemoglobinopathy S, Depranocytosis or Sickle Cell Disease is the most common
      hemoglobinopathy in the world. In its heterozygous form (Sickle Cell Trait), it
      affects 8% of the black population in the U.S. and 25% of the black population in
      Africa, and is found less frequently in the Mediterranean area, India, Middle
      East and Latin America. The basic alteration is a substitution of glutamic acid
      by valin in the sixth position of the beta globin chain, which causes
      polymerization at low oxygen tension thereby distorting the structure of
      erythrocytes and increasing blood viscosity, which, in turn, generates
      obstructions of the capillary arterial blood flow to different areas of the body
      thus causing microinfarctions. Although Splenic Infarction is rare, it is
      recognized as a serious complication of Heterozygous Sickle Cell Disease (Sickle
      Cell Trait). We present the case of a 21 year-old mestizo male patient who came
      in with an acute case of abdominal pain after arriving to work in the Casapalca
      mining city (located in the Peruvian Andes at 4200 m.a.s.l.) and was referred to
      our Hospital in Lima for exams. We present the case because it is an unusual
      cause of acute abdominal pain, and because this condition is rare in Peru and
      there are few publications about it.

PMID- 17211490
TI  - [Primary lymphoma of pancreas].
AB  - Pcreas lymphoma is very rare, we report a 29 years old man, treated at Daniel A.
      Carrion Hospital. He presented jaudince and abdominal pain . Ecography and
      tomography showed a mass in pcreas head . the patient underwent
      pancreaticoduodenectomy. The final diagnosis was Large B cell diffuse lymphoma.
      CD 20 +, CD3 -, CD45 + without extrapancreatic disease, ACE -. We report the case
      and literature review.

PMID- 17211491
TI  - Relative energies of binding for antibody-carbohydrate-antigen complexes computed
      from free-energy simulations.
AB  - Free-energy perturbation (FEP) simulations have been applied to a series of
      analogues of the natural trisaccharide epitope of Salmonella serotype B bound to
      a fragment of the monoclonal anti-Salmonella antibody Se155-4. This system was
      selected in order to assess the ability of free-energy perturbation (FEP)
      simulations to predict carbohydrate-protein interaction energies. The ultimate
      goal is to use FEP simulations to aid in the design of synthetic high affinity
      ligands for carbohydrate-binding proteins. The molecular dynamics (MD)
      simulations were performed in the explicit presence of water molecules, at room
      temperature. The AMBER force field, with the GLYCAM parameter set for
      oligosaccharides, was employed. In contrast to many modeling protocols, FEP
      simulations are capable of including the effects of entropy, arising from
      differential ligand flexibilities and solvation properties. The experimental
      binding affinities are all close in value, resulting in small relative free
      energies of binding. Many of the DeltaDeltaG values are on the order of 0-1 kcal
      mol(-1), making their accurate calculation particularly challenging. The
      simulations were shown to reasonably reproduce the known geometries of the
      ligands and the ligand-protein complexes. A model for the conformational behavior
      of the unbound antigen is proposed that is consistent with the reported NMR data.
      The best agreement with experiment was obtained when histidine 97H was treated as
      fully protonated, for which the relative binding energies were predicted to well
      within 1 kcal mol(-1). To our knowledge this is the first report of FEP
      simulations applied to an oligosaccharide-protein complex.

PMID- 17211492
TI  - Exploring perceptions of interprofessional collaboration in child mental health
      care.
AB  - PURPOSE: This paper proposes a tentative theoretical model (PINCOM) and a measure
      of mental health and school professionals' perception of interprofessional
      collaboration (IPC). THEORY: The model is based on twelve constructs derived from
      a pilot study, organizational and social psychology. The main aim of the model is
      to capture central aspects of IPC. METHOD: A forty-eight item self-report
      questionnaire (PINCOM-Q) was designed to explore professionals' perceptions of
      IPC. The sample (n=134) included professionals who worked in primary care,
      specialist services and in elementary schools. Exploratory factor analyses and
      reliability testing were conducted to reduce the large number of variables in the
      questionnaire. RESULTS: RESULTS INDICATE THAT CENTRAL ASPECTS OF IPC IN THE
      CONTEXT OF SERVICE DELIVERY AND CASE WORK ARE: interprofessional climate,
      organizational culture, organizational aims, professional power, group leadership
      and motivation. CONCLUSION: Preliminary empirical testing of the questionnaire
      demonstrated that it is possible to measure perceptions of IPC, with reasonable
      levels of construct validity and reliability. DISCUSSION: Further, revision of
      the questionnaire is discussed to make it fit for use in large scale studies with
      the purpose of enhancing (a) the validity of the PINCOM model, and (b) the
      quality of mental health services that are based on IPC.

PMID- 17211493
TI  - Developing youth care: the challenge of integrated school health promotion.

PMID- 17211495
TI  - Low socio-economic status, smoking, mental stress and obesity predict obstructive
      symptoms in women, but only smoking also predicts subsequent experience of poor
      health.
AB  - This study was conducted among female subjects to assess the possible association
      between selected risk factors and lung function as well as airway symptoms in a
      32-year perspective. The Prospective Population Study of Women was initiated in
      1968-1969 in Goteborg, Sweden (population about 450,000) with follow-ups in 1974
      1975, 1980-1981, 1992-1993 and 2000-2001. Women born in 1930, representative of
      women of the same age in the general population in 1968, were selected.
      Initially, 372 participants were included in the cohort. In 2000-2001, 231 of
      these women (73%), now 70 years old, underwent lung function tests. The main
      outcome measures were lung function values, airway symptoms and health outcome in
      2000-2001 in relation to self-reported exposures in 1968-1969 including smoking
      status. Smoking in 1968-1969 was associated with self-reported chronic
      bronchitis, obstructive symptoms and poor health 32 years later as well as lower
      lung function values, compared to non-smokers. Obesity, low socio-economic status
      and self-reported mental stress in 1968-1969 were associated with obstructive
      symptoms 32 years later. There are only a few longitudinal studies concerning
      women's health problems in this field and epidemiological studies of lung
      function impairment in women and risk factors in a long-term perspective are
      scarce. The results of the study suggest that life-style factors such as mental
      stress, obesity and smoking among women are related to airway symptoms and also
      quality of life many years later.

PMID- 17211494
TI  - Grb2-associated binder 1 polymorphism was associated with the risk of
      Helicobactor pylori infection and gastric atrophy.
AB  - BACKGROUND: Various single nucleotide polymorphisms (SNPs) have explained the
      association between Helicobacter pylori (H. pylori) and gastric atrophy and
      cancer. This study investigated the associations of Grb2 associated binder 1
      (Gab1) polymorphism and the combination of PTPN11 gene encoding src homology 2
      domain-containing protein tyrosine phosphatase-2 (SHP2) and Gab1 gene with
      gastric cancer and gastric atrophy among H. pylori seropositive subjects.
      METHODS: A single nucleotide polymorphism at intron 2 of Gab1 (JST164345) was
      examined for 454 Japanese health checkup examinees (126 males and 328 females)
      aged 35 to 85 without a history of gastric cancer and 202 gastric cancer patients
      (134 males and 68 females) aged 33 to 94 with pathologically confirmed diagnosis
      of gastric adenocarcinoma. RESULTS: The decreased OR of the Gab1 A/A for H.
      pylori seropositivity was 0.25 (95% confidence interval (CI): 0.08-0.71). Among
      seropositive healthy controls, the OR of the Gab1 G/A+A/A for gastric atrophy was
      significant (OR=1.95, 95% CI: 1.12 -3.40). Seropositive individuals with PTPN11
      G/G and Gab1 G/A+A/A demonstrated the highest risk of gastric atrophy with
      significance (OR=3.49, 95% CI: 1.54-7.90) relative to PTPN11 G/A+A/A and Gab1
      G/G, the lowest risk combination, as a reference. However, the gene-gene
      interaction between PTPN11 and Gab1 was not observed (OR=1.39, 95% CI: 0.41
      4.66). Compared to gastric cancer case, the Gab1 did not influence the step of
      atrophy/metaplasia-gastric cancer sequence. CONCLUSIONS: This study represents
      that the Gab1 polymorphism was associated with the low risk of H. pylori
      infection and the high risk of gastric atrophy among seropositive healthy
      controls, and that seropositive individuals with PTPN11 G/G and Gab1 G/A+G/G were
      associated with the greatest risk of gastric atrophy. These findings require
      confirmation in much larger studies.

PMID- 17211496
TI  - HIV DNA and dementia in treatment-naive HIV-1-infected individuals in Bangkok,
      Thailand.
AB  - High HIV-1 DNA (HIV DNA) levels in peripheral blood mononuclear cells (PBMC)
      correlate with HIV-1-associated dementia (HAD) in patients on highly active
      antiretroviral therapy (HAART). If this relationship also exists among HAART
      naive patients, then HIV DNA may be implicated in the pathogenesis of HAD. In
      this study, we evaluated the relationship between HIV DNA and cognition in
      subjects naive to HAART in a neuro AIDS cohort in Bangkok, Thailand. Subjects
      with and without HAD were recruited and matched for age, gender, education, and
      CD4 cell count. PBMC and cellular subsets were analyzed for HIV DNA using real
      time PCR. The median log(10) HIV DNA copies per 10(6) PBMC for subjects with HAD
      (n=15) was 4.27, which was higher than that found in subjects without dementia
      (ND; n=15), 2.28, p<0.001. This finding was unchanged in a multivariate model
      adjusting for plasma HIV-1 RNA levels. From a small subset of individuals, in
      which adequate number of cells were available, more HIV DNA was in
      monocytes/macrophages from those with HAD compared to those with ND. These
      results are consistent with a previous report among HAART-experienced subjects,
      thus further implicating HIV DNA in the pathogenesis of HAD.

PMID- 17211498
TI  - Functional genomics analysis of low concentration of ethanol in human
      hepatocellular carcinoma (HepG2) cells. Role of genes involved in transcriptional
      and translational processes.
AB  - We previously found that ethanol at millimolar level (1 mM) activates the
      expression of transcription factors with subsequent regulation of apoptotic genes
      in human hepatocellular carcinoma (HCC) HepG2 cells. However, the role of ethanol
      on the expression of genes implicated in transcriptional and translational
      processes remains unknown. Therefore, the aim of this study was to characterize
      the effect of low concentration of ethanol on gene expression profiling in HepG2
      cells using cDNA microarrays with especial interest in genes with transcriptional
      and translational function. The gene expression pattern observed in the ethanol
      treated HepG2 cells revealed a relatively similar pattern to that found in the
      untreated control cells. The pairwise comparison analysis demonstrated four
      significantly up-regulated (COBRA1, ITGB4, STAU2, and HMGN3) genes and one down
      regulated (ANK3) gene. All these genes exert their function on transcriptional
      and translational processes and until now none of these genes have been
      associated with ethanol. This functional genomic analysis demonstrates the
      reported interaction between ethanol and ethanol-regulated genes. Moreover, it
      confirms the relationship between ethanol-regulated genes and various signaling
      pathways associated with ethanol-induced apoptosis. The data presented in this
      study represents an important contribution toward the understanding of the
      molecular mechanisms of ethanol at low concentration in HepG2 cells, a HCC
      derived cell line.

PMID- 17211499
TI  - Short-term success of osseointegrated dental implants in HIV-positive
      individuals: a prospective study.
AB  - PURPOSE: Except for the occasional case report, there are no studies evaluating
      the success rate of osseointegrated dental implants in individuals infected with
      the human immunodeficiency virus (HIV). This study investigated the short-term
      clinical outcome of implant placement in a group of HIV-positive and HIV-negative
      individuals who required complete dentures. METHODS AND MATERIALS: Edentulous
      subjects were recruited from an HIV-dedicated clinic and a dental school clinic.
      Two BioHorizons dental implants were placed in the anterior mandible to support
      an overdenture opposing a maxillary denture. Outcome measurements obtained six
      months after activation of implants were presence of pain, mobility, soft tissue
      status, and radiographic bone level. Descriptive statistics were used. RESULTS:
      Twenty-nine edentulous adults, including 20 HIV-positive subjects (test) and nine
      HIV-negative subjects (control), participated. The test group had six females, 14
      males; 13 Whites, four African-Americans, and three Hispanics with a mean age of
      48.9 years (range: 35-59). The mean CD4 count was 467 cells/mm3 (range: 132-948).
      The control group had six females, three males; seven Whites, and two Hispanics
      with a mean age of 65.3 years (range: 50-82). Short-term success rate was 100%
      for both groups. No difference in clinical outcome was found between the groups.
      CONCLUSION: This study demonstrated dental implants are well tolerated and have
      predictable outcomes for HIV-infected individuals for the duration of the study
      and probably over an even longer term.

PMID- 17211497
TI  - Strength training improves muscle quality and insulin sensitivity in Hispanic
      older adults with type 2 diabetes.
AB  - Hispanics are at increased risk of morbidity and mortality due to their high
      prevalence of diabetes and poor glycemic control. Strength training is the most
      effective lifestyle intervention to increase muscle mass but limited data is
      available in older adults with diabetes. We determined the influence of strength
      training on muscle quality (strength per unit of muscle mass), skeletal muscle
      fiber hypertrophy, and metabolic control including insulin resistance
      (Homeostasis Model Assessment -HOMA-IR), C-Reactive Protein (CRP), adiponectin
      and Free Fatty Acid (FFA) levels in Hispanic older adults. Sixty-two community
      dwelling Hispanics (>55 y) with type 2 diabetes were randomized to 16 weeks of
      strength training plus standard care (ST group) or standard care alone (CON
      group). Skeletal muscle biopsies and biochemical measures were taken at baseline
      and 16 weeks. The ST group show improved muscle quality (mean+/-SE: 28+/-3) vs
      CON (-4+/-2, p<0.001) and increased type I (860+/-252 microm(2)) and type II
      fiber cross-sectional area (720+/-285 microm(2)) compared to CON (type I: -164+/
      290 microm(2), p=0.04; and type II: -130+/-336 microm(2), p=0.04). This was
      accompanied by reduced insulin resistance [ST: median (interquartile range) 
      0.7(3.6) vs CON: 0.8(3.8), p=0.05]; FFA (ST: -84+/-30 micromol/L vs CON: 149+/-48
      micromol/L, p=0.02); and CRP [ST: -1.3(2.9) mg/L vs CON: 0.4(2.3) mg/L, p=0.05].
      Serum adiponectin increased with ST [1.0(1.8) microg/mL] compared to CON [
      1.2(2.2) microg/mL, p<0.001]. Strength training improved muscle quality and whole
      body insulin sensitivity. Decreased inflammation and increased adiponectin levels
      were related with improved metabolic control. Further studies are needed to
      understand the mechanisms associated with these findings. However, these data
      show that strength training is an exercise modality to consider as an adjunct of
      standard of care in high risk populations with type 2 diabetes.

PMID- 17211500
TI  - A scanning electron microscopic evaluation of root canal wall cleanliness after
      calcium hydroxide removal using three irrigation regimens.
AB  - AIMS: The aims of this in vitro study were to evaluate debris and smear layer
      elimination capability effectiveness of 5.25% sodium hypochlorite (NaOCl) after
      calcium hydroxide removal from the root canal and to determine if
      ethylenediaminetetraacetic acid (EDTA) and citric acid have any additional
      effects on debris and smear layer removal. METHODS AND MATERIALS: All irrigation
      regimens are associated with ultrasonics. Thirty-six pulpless single-rooted teeth
      were divided into three groups on the basis of the irrigation regimen, namely
      5.25% NaOCl alone, 5.25% NaOCl with 17% EDTA pH 7 (NaOCl-EDTA), and 5.25% NaOCl
      with 50% citric acid (NaOCl-CA). All root canals were instrumented with the
      Protaper rotary system (Dentsply-Maillefer, Ballaigues, Switzerland) using a
      crown-down approach. The apical foramen of each tooth was enlarged to a size 30
      with a 0.09 taper. After longitudinal sectioning, the dentin walls were
      microphotographed using scanning electron microscopy (SEM) at a 1500x
      magnification. Using a grid and a 5-step scale these microphotographs were scored
      by three investigators in order to evaluate debris and smear layer residuals.
      Data were statistically evaluated using Kruskal-Wallis and Mann-Whitney tests.
      RESULTS: In the coronal third the lowest score obtained with NaOCl-CA was similar
      to NaOCl-EDTA. When using NaOCl-EDTA, mean debris scores were similar to the
      control group (NaOCl) and lower than NaOCl-CA in the middle and apical thirds.
      Regarding the mean smear layer score, NaOCl-CA was the lowest in the coronal,
      middle, and apical thirds with a statistically significant difference (p <
      0.001). CONCLUSION: When the total surface of the root was evaluated, NaOCl-EDTA
      was superior in removing debris, but the association of NaOCl-CA enabled the most
      effective removal of the smear layer.

PMID- 17211501
TI  - Marginal and internal adaptation of commercially pure titanium and titanium
      aluminum-vanadium alloy cast restorations.
AB  - AIM: The purpose of this in vitro study was to investigate the marginal accuracy
      and internal fit of complete cast crowns and three-unit fixed partial dentures
      (FPDs) cast with commercially pure titanium (CPTi) and Titanium-Aluminum-Vanadium
      alloy (Ti-6Al-4V). METHODS AND MATERIALS: CPTi and Ti-6Al-4V alloy were used to
      cast twelve single crowns and twelve three-unit FPDs. A traveling microscope was
      used to measure marginal gap and discrepancies in internal fit. Two and one-way
      analysis of variance (ANOVA) analyses were used to determine the effects of the
      marginal and internal fit discrepancies. RESULTS: The Ti-6Al-4V alloy
      demonstrated a significantly smaller marginal gap than CPTi (P<0.0001). The
      recorded marginal discrepancies for both metals were within a clinically accepted
      range (<100 microm). The single crown fit discrepancy was significantly smaller
      than the three-unit FPD for both the CPTi and the Ti-6Al-4V alloy (P<0.0001). For
      the internal fit discrepancy, the occlusal surface showed the greatest gaps.
      CONCLUSIONS: The Ti-6Al-4V alloy demonstrated a better fit than CPTi. Single
      crowns showed an improved fit when compared with the three-unit FPD. Mid-occlusal
      internal gap demonstrated greater values than the axial internal gap. CLINICAL
      IMPLICATIONS: This in vitro study suggested marginal fit of complete crowns and
      three-unit FPDs cast by CPTi or Ti-6Al-4V alloy were within the range of what is
      clinically acceptable for longevity of restorations.

PMID- 17211502
TI  - The effect of finishing and polishing procedures on the surface roughness of
      composite resin materials.
AB  - AIMS: The aims of this study were to evaluate the effect of various finishing and
      polishing procedures on the surface roughness of six different composite resin
      materials (Artemis Enamel, TPH Spectrum, Filtek A-110, Filtek Supreme Enamel,
      Solitaire 2, and Filtek P-60) as well as to evaluate the effectiveness of the
      surface sealant application (BisCover) on the surface roughness after finishing
      and polishing procedures of tested composites. METHODS AND MATERIALS: Specimens
      (n=168) measuring 5 mm in diameter x 2 mm in thickness were fabricated in a
      plexiglass well covered with a Mylar strip using six composite resins. A control
      group of seven specimens of each material received no polishing after being cured
      under the Mylar strip. Twenty-one specimens for each composite were randomly
      divided among three finishing and polishing groups (n=7). Each group was polished
      using a different system: Carbide bur/Sof-Lex disc, Carbide bur/Enhance disc with
      polishing paste, and Carbide bur/Edenta composite finishing kit. The average
      surface roughness (Ra, microm) of the control and treated specimens were measured
      with the Mitutoyo Surftest-402 Surface Roughness tester. After a surface sealant
      (BisCover) was applied to all treated specimens, according to manufacturer's
      instructions, the average roughness (Ra) was measured again. Results were
      statistically analyzed using analysis of variance (ANOVA) and the post-hoc
      Scheffe's test at a p<0.05 significance level. RESULTS: Significant differences
      were found for the surface roughness (p<0.05) with interaction among composite
      resins and the finishing systems used (p<0.05). Enhance/Biscover finishing and
      polishing procedure surface was not significantly different from the Mylar strip
      surface groups (p>0.05). The Mylar strip group was not significantly different
      from the Sof-Lex/BisCover and Edenta/BisCover groups. The ranking of mean Ra
      values by materials was as follows: Filtek Supreme Enamel < Filtek A110 < TPH
      Spectrum < Artemis <Filtek P-60 < Solitaire 2. The ranking of mean Ra values by
      polishing systems was as follows: Enhance/BisCover < Mylar Strip < Sof
      Lex/BisCover < Edenta/BisCover < Sof-Lex < Enhance < Edenta. CONCLUSION: Smoother
      surfaces were recorded for the Enhance/BisCover and the Mylar strip-formed
      surface groups. The composite finishing kit Edenta significantly increased the Ra
      for all tested composites (p<0.05). But after finishing with Edenta, the use of a
      surface sealant (BisCover) significantly improved the surface smoothness of all
      tested composites (p<0.05). Use of BisCover surface sealant on anterior and
      posterior resin composite restorations after finishing and polishing procedures
      is recommended.

PMID- 17211503
TI  - Effect of different types of enamel conditioners on the bond strength of
      orthodontic brackets.
AB  - AIM: A unique characteristic of some new bonding systems in operative dentistry
      is they combine conditioning and priming agents into a single acidic primer
      solution for simultaneous use on both enamel and dentin. Combining conditioning
      and priming into a single treatment step results in improvement in both time and
      cost-effectiveness to the clinician and, indirectly, to the patient. The purpose
      of this study was to determine the effects of the use of a self-etching primer on
      the bond strength of orthodontic brackets and on the bracket/adhesive failure
      mode. METHODS AND MATERIALS: Thirty-six fresh bovine incisors were collected and
      stored in a solution of 0.1% (weight/volume) thymol. The criteria for tooth
      selection included intact buccal enamel, no cracks caused by the presence of the
      extraction forceps, and no defects. The teeth were cleansed and polished with
      pumice and rubber prophylactic cups for ten seconds. Brackets were bonded to the
      teeth according to one of three protocols following the manufacturers'
      instructions--Group 1: Conventional multistep bonding system (control group)
      (n=12); Group 2: Self-etching primer system (n=12); and Group 3: Acid+self
      etching primer system (n=12). Specimens were loaded to failure in a Zwick test
      machine (Zwick GmbH & Co, Ulm, Germany). Shear bond strengths were measured at a
      crosshead speed of 5 mm/min. RESULTS: The mean shear bond strength in megapascals
      (Mpa) (standard deviation) were 11.7 (4.2), 10.5 (4.4), and 10.9 (4.8) for Groups
      1, 2, and 3, respectively. The analysis of variance (ANOVA) was used to compare
      the three groups. The results indicated no significant difference in the bond
      strength between the three groups (P=0.800). The results of the Chi square test,
      evaluating the residual adhesives on the enamel surfaces, revealed no significant
      difference between the three groups (P=0.554). CONCLUSION: Results of the present
      in vitro study indicate the use of self-etching primers may be an alternative to
      conventional phosphoric acid pre-treatment in orthodontic bonding.

PMID- 17211504
TI  - Fracture resistance of various temporary crown materials.
AB  - AIM: The aim of this study was to evaluate the fracture resistance of various
      provisional crown materials using an in vitro model test system. METHODS AND
      MATERIALS: In the present study polycarbonate crowns, prefabricated by the
      manufacturer (3M Polycarbonate Crown), and the temporary crowns, fabricated in
      the dental laboratory environment, were fabricated using bis-acryl composite
      (Protemp II), autopolymerizing PMMA resin (BISICO Temp S), and heat-polymerized
      PMMA resin (Major C&B-V Dentine). All temporary crowns were stored in distilled
      water for 24 hours at room temperature prior to testing. The crowns were seated
      on metal dies, fabricated from Cr-Co alloy (AZ Dental, Konstanz, Germany), and
      then tested using the indenter of a Hounsfield testing machine (Hounsfield
      Tensometer, Hounsfield Test Equipment, Raydon, England). The tip of the indenter
      was located at a position one-third of the way down the inciso-palatine surface
      at 135 masculine. The data were statistically analyzed for differences using one
      way analysis of variance (ANOVA) and the Tukey HSD test (P < .05). Additionally,
      the types of failure obtained from the fracture load test were examined using 10x
      magnification with a stereo microscope. RESULTS: The results of the present study
      indicated polycarbonate crowns were significantly different from the BISICO Temp
      S, Protemp II, and Major C&B-V Dentine (P < .05) groups. CONCLUSION: This in
      vitro study shows polycarbonate crowns may be preferable to the other types of
      temporary crowns used in this study.

PMID- 17211505
TI  - Influence of trans-operative complications on socket healing following dental
      extractions.
AB  - AIM: Extraction healing complications have been attributed to several factors.
      The influence of trans-operative complications on an extraction site wound
      healing was the focus of this investigation. METHODS AND MATERIALS: This
      prospective study was conducted at the Oral Surgery Clinic of the Department of
      Oral and Maxillofacial Surgery of the Lagos University Teaching Hospital (LUTH)
      in Nigeria . Subjects selected were those referred for one or two adjacent
      extractions and who satisfied the inclusion criteria for the study. The relevant
      pre-operative information recorded for each patient were age and sex of patient,
      indications for extraction, time taken to extract the tooth, tooth/teeth removed,
      and any trans-operative complications. Extractions were performed with dental
      forceps, elevators, or both under local anaesthesia. Patients were blindly
      evaluated on the third and seventh post-operative day for socket healing
      assessment without reference to pre-operative information on the patients.
      RESULTS: Seventy-three (24.25%) of 301 teeth considered for socket healing
      assessment had various trans-operative complications due to accidental crown,
      root, or alveolar bone fractures. Of the 73 extractions with trans-operative
      complications during extraction, 18 developed a socket healing complication,
      while 17 of the 228 extractions without trans-operative complications developed
      socket healing complications (p = .000). The mean (SD) time taken to extract
      teeth developing healing complications was also found to be significantly longer
      than those without healing complications (p < .01). CONCLUSIONS: The study
      demonstrated the combination of tooth/bone fragments in the socket and increased
      time of extraction due to trans-operative complications and accidents predispose
      to the development of extraction site wound healing disturbance.

PMID- 17211506
TI  - Prevalence of medical conditions among patients attending dental teaching clinics
      in northern Jordan.
AB  - AIM: This study was conducted to estimate the prevalence of self reported medical
      conditions among dental patients attending dental teaching clinics in north
      Jordan. METHODS AND MATERIALS: A total of 1,509 patients were included, of which
      46.1% were males and 53.9% were females. All age groups were included and ranged
      between 14 and 78 years. The findings were analyzed in relation to age and
      gender. RESULTS: Overall, gastrointestinal disease was most prevalent (11.9%),
      followed by bleeding tendencies (9.3%), renal disorders (8.7%), respiratory
      disease (8.3%), and hypertension (6.4%). Only 3.2% of the participants reported
      having antibiotics prescribed for them prior to a dental procedure for
      prophylactic purposes. CONCLUSION: Due to the high frequency of medical
      conditions, thorough evaluation of patients' medical and dental care histories
      should be a mandatory first step in their management.

PMID- 17211507
TI  - A comparative evaluation of self-reported oral hygiene practices among medical
      and engineering university students with access to health-promotive dental care.
AB  - AIM: This study was conducted to test the null hypothesis that no difference
      exists in the oral hygiene knowledge and practices of university students in
      different courses when they have equal opportunity to access health-promotive
      dental care. METHODS AND MATERIALS: The study was conducted using 120 students
      each from the medical and engineering colleges at the University of Manipal
      Academy of Higher Education who had easy access to the dental college within the
      campus which provides health-promotive dental care to all its patients. A self
      administered structured questionnaire consisting of questions on demographic
      data, oral hygiene knowledge and practices, and dental service utilization
      patterns was distributed among the students. The data collected was analyzed
      using SPSS 10 version. RESULTS: Statistically significant differences were found
      between the two groups with respect to the knowledge of fluoridated toothpastes,
      frequency of toothbrush renewal, use of dental floss, and a tongue cleaner (p <
      0.001). The groups were similar in all other practices including the utilization
      of dental services. There were no significant differences between the self
      reported oral hygiene knowledge and practices among medical and engineering
      university students, but the knowledge levels of the students were considerably
      lower than expected.

PMID- 17211508
TI  - Oral care in the intensive care unit: a review.
AB  - Oral care for patients in the hospital's Intensive Care Unit (ICU) is important,
      but this is usually the responsibility of nurses without sufficient knowledge in
      oral care or comprehensive protocols to follow. The problems of maintaining oral
      care with oral intubation, performing oral assessment, guidelines for oral
      hygiene care, frequency of oral care needed, and suggested mouth care protocol
      followed by recommendations are presented and discussed in this paper.

PMID- 17211509
TI  - Tongue piercing: case report of a local complication.
AB  - Historically, wearing adornments on pierced body parts has been associated with
      many cultures as manifestations of religious or cultural identities. Currently,
      its use has a broad acceptance among young people. The most common sites for
      piercings are the tongue and lower lip in the oral cavity. Several complications
      may be associated with this practice with the most frequently observed being
      halitosis, periodontitis, tooth fracture, glossitis, and the formation of
      abscesses. This paper is a case report of a patient who had a complication from a
      piercing on the tongue located under the overlying mucosa. It also suggests a
      local habit was a possible initiator of this complication.

PMID- 17211510
TI  - Long-term uncontrolled hereditary gingival fibromatosis: a case report.
AB  - Hereditary gingival fibromatosis (HGF) is a rare condition characterized by
      varying degrees of gingival hyperplasia. Gingival fibromatosis usually occurs as
      an isolated disorder or can be associated with a variety of other syndromes. A 33
      year-old male patient who had a generalized severe gingival overgrowth covering
      two thirds of almost all maxillary and mandibular teeth is reported. A
      mucoperiosteal flap was performed using interdental and crevicular incisions to
      remove excess gingival tissues and an internal bevel incision to reflect flaps.
      The patient was treated 15 years ago in the same clinical facility using the same
      treatment strategy. There was no recurrence one year following the most recent
      surgery.

PMID- 17211511
TI  - AAOMP case challenge: diffuse lip swelling.

PMID- 17211512
TI  - Serial analysis of gene expression in sugarcane (Saccharum spp.) leaves revealed
      alternative C4 metabolism and putative antisense transcripts.
AB  - Sugarcane (Saccharum spp.) is a highly efficient biomass and sugar producing
      crop. Leaf reactions have been considered as potential rate-limiting step for
      sucrose accumulation in sugarcane stalks. To characterize the sugarcane leaf
      transcriptome, field-grown mature leaves from cultivar "SP80-3280" were analyzed
      using Serial Analysis of Gene Expression (SAGE). From 480 sequenced clones, 9,482
      valid tags were extracted, with 5,227 unique sequences, from which 3,659 (70%)
      matched at least a sugarcane assembled sequence (SAS) with putative function;
      while 872 tags (16.7%) matched SAS with unknown function; 523 (10%) matched SAS
      without a putative annotation; and only 173 (3.3%) did not match any sugarcane
      ESTs. Based on gene ontology (GO), photosystem (PS) I reaction center was
      identified as the most frequent gene product location, followed by the remaining
      sites of PS I, PS II and thylakoid complexes. For metabolic processes,
      photosynthesis light harvesting complexes; carbon fixation; and chlorophyll
      biosynthesis were the most enriched GO-terms. Considering the alternative
      photosynthetic C(4) cycles, tag frequencies related to phosphoenolpyruvate
      carboxykinase (PEPCK) and aspartate aminotransferase compared to those for
      NADP(+)-malic enzyme (NADP-ME) and NADP-malate dehydrogenase, suggested that
      PEPCK-type decarboxylation appeared to predominate over NADP-ME in mature leaves,
      although both may occur, opposite to currently assumed in sugarcane. From the
      unique tag set, 894 tags (17.1%) were assigned as potentially derived from
      antisense transcripts, while 73 tags (1.4%) were assigned to more than one SAS,
      suggesting the occurrence of alternative processing. The occurrence of antisense
      was validated by quantitative reverse transcription amplification. Sugarcane leaf
      transcriptome provided new insights for functional studies associated with
      sucrose synthesis and accumulation.

PMID- 17211513
TI  - ci21A/Asr1 expression influences glucose accumulation in potato tubers.
AB  - Asr genes are exclusively found in the genomes of higher plants. In many species,
      this gene family is expressed under abiotic stress conditions and during fruit
      ripening. The encoded proteins have nuclear localisation and consequently a
      transcription factor function has been suggested. Interestingly, yeast-one-hybrid
      experiments revealed that a grape ASR binds to the promoter of a hexose
      transporter gene (VvHT1). However, the role of these proteins in planta is still
      elusive. By using a reverse genetics approach in potato we found that
      modification of Asr1 expression has no incidence on the aerial phenotype of the
      plant but exerts a dramatic effect in tuber. Asr1 antisense potatoes displayed
      decreased tuber fresh weight whereas Asr1 overexpressors had a diminished number
      of tubers. Moreover, overexpression lines showed lower transcript levels of a
      plasma membrane hexose transporter and a concomitant decrease in glucose content
      in parenchyma cells of potato tubers. On the same hand glucose uptake rate was
      also reduced in one of the overexpressing lines. It thus seems likely that Asr1
      is involved in the control of hexose uptake in heterotrophic organs. In addition,
      the transgenic plants were characterized by several other changes in steady state
      metabolite levels. Results presented here support a role for ci21A/Asr1 in
      glucose metabolism of potato tuber.

PMID- 17211514
TI  - Interaction network of proteins associated with abiotic stress response and
      development in wheat.
AB  - Wheat is the most widely adapted crop to abiotic stresses and considered an
      excellent system to study stress tolerance in spite of its genetic complexity.
      Recent studies indicated that several hundred genes are either up- or down
      regulated in response to stress treatment. To elucidate the function of some of
      these genes, an interactome of proteins associated with abiotic stress response
      and development in wheat was generated using the yeast two-hybrid GAL4 system and
      specific protein interaction assays. The interactome is comprised of 73 proteins,
      generating 97 interactions pairs. Twenty-one interactions were confirmed by
      bimolecular fluorescent complementation in Nicotiana benthamiana. A confidence
      scoring system was elaborated to evaluate the significance of the interactions.
      The main feature of this interactome is that almost all bait proteins along with
      their interactors were interconnected, creating a spider web-like structure. The
      interactome revealed also the presence of a "cluster of proteins involved in
      flowering control" in three- and four-protein interaction loops. This network
      provides a novel insight into the complex relationships among transcription
      factors known to play central roles in vernalization, flower initiation and
      abscisic acid signaling, as well as associations that tie abiotic stress with
      other regulatory and signaling proteins. This analysis provides useful
      information in elucidating the molecular mechanism associated with abiotic stress
      response in plants.

PMID- 17211515
TI  - Transcriptional profiling of wheat caryopsis development using cDNA microarrays.
AB  - The expression of 7,835 genes in developing wheat caryopses was analyzed using
      cDNA arrays. Using a mixed model analysis of variance (ANOVA) method, 29% (2,237)
      of the genes on the array were identified to be differentially expressed at the 6
      different time-points examined, which covers the developmental stages from
      coenocytic endosperm to physiological maturity. Comparison of genes
      differentially expressed between two time-points revealed a dynamic transcript
      accumulation profile with major re-programming events that occur at 3-7, 7-14 and
      21-28 DPA. A k-means clustering algorithm grouped the differentially expressed
      genes into 10 clusters, revealing co-expression of genes involved in the same
      pathway such as carbohydrate and protein synthesis or preparation for
      desiccation. Functional annotation of genes that show peak expression at specific
      time-points correlated with the developmental events associated with the
      respective stages. Results provide information on the temporal expression during
      caryopsis development for a significant number of differentially expressed genes
      with unknown function.

PMID- 17211517
TI  - A novel polymorphisms in intron 12 of the bovine calpastatin gene.
AB  - Calpastatin (CAST) is a specific inhibitor of the ubiquitous calcium-dependent
      proteases-mu-calpain and m-calpain, found in mammalian tissues. This proteolytic
      system plays a key role in the tenderization process that occurs during post
      mortem storage of meat under refrigerated conditioning. Fragments of the bovine
      CAST gene including intron 12 were amplified and subjected to SSCP analysis. Four
      new SNPs were found within intron 12 of the CAST gene: a transition T/C at
      position 3893+155* A/G at position 3893+163, a transversion T/A at position
      3893+223 and a substitution A/G at position 3893+428 (consensus sequence--GenBank
      AY834771). The genetic variants in the bovine CAST gene can be analyzed with RFLP
      method and was studied in 375 bulls of six breeds, including Hereford, Aberdeen
      angus, Simmental, Charolaise, Limousine and Polish Black-and-White (BW; Fresian)
      breeds.

PMID- 17211516
TI  - Construction of cytoplasmic molecular markers distinguishing Danio rerio from
      Gobiocypris rarus at high identity domains based on MP-PCR strategy and Sybr
      Green I detection.
AB  - To distinguish the cytoplasm of Danio rerio from that of Gobiocypris rarus, we
      cloned G. rarus COXI and constructed cytoplasmic molecular markers at the high
      identity domains of COXI by mutated primer PCR (MP-PCR for short). Then Sybr
      Green I was used to detect the single amplicon. As a result, we succeeded in
      getting the cytoplasmic molecular markers, G.M COXI and Z.M COXI, by MP-PCR
      strategy. They were used to detect the sperm-derived mtDNA in the sexual hybrid
      embryos (D. rerio female symbolxG. rarus male symbol) before the sphere stage. In
      the present study, all results demonstrate that MP-PCR approach and Sybr Green I
      detection are feasible to construct the molecular markers to identify genes that
      shared high identity.

PMID- 17211518
TI  - Characterisation of the nascent polypeptide-associated complex in fission yeast.
AB  - The nascent polypeptide-associated complex (NAC) is an abundant and
      phylogenetically conserved protein complex. It is composed of two subunits and
      interacts with nascent polypeptide chains emerging from the ribosome. It has been
      proposed to protect the nascent chains from premature interaction with other cell
      proteins, but has also been found to associate with DNA junctions, and to be
      involved in other processes including transcription regulation and mitochondrial
      protein import.Here, we characterize NAC in fission yeast. We find that NAC is
      associated with ribosomes, while a significant fraction remains in a free form.
      The NAC alpha subunit contains a ubiquitin-associated (UBA) domain, which is
      found in several proteins involved in the ubiquitin-proteasome pathway for
      protein degradation. However, NAC does not associate with ubiquitin chains and
      mutants lacking NAC did not exhibit any obvious defects in protein degradation.
      Accordingly, we find that the NAC UBA domain belongs to an ancient and distinct
      subgroup of the UBA family. In contrast to the situation with budding yeast,
      fission yeast cells devoid of NAC were not temperature sensitive. However, they
      displayed resistance to the amino acid analogue canavanine, in accordance with
      the idea that NAC is involved in protein quality control.

PMID- 17211519
TI  - Characterization of the human ADAMTS-5 (aggrecanase-2) gene promoter.
AB  - Aggrecan degradation in osteoarthritis is mediated primarily by aggrecanases (-1
      and -2) that are members of the ADAMTS family of proteases. Aggrecanase-2 (ADAMTS
      5) null mice are resistant to aggrecan degradation in models of experimentally
      induced osteoarthritis. In order to analyze ADAMTS-5 gene expression at the
      transcriptional level, we have cloned a 2.6 kb promoter region (-2096 to +506) of
      the human ADAMTS-5 gene and generated betagal reporter constructs. Promoter
      functionality was tested in transient transfection assays in chondrocytic cells.
      Analysis of the 2.6 kb promoter sequence indicated four putative binding sites
      for the Runx family of transcription factors, of which one member, Runx2, plays a
      role in chondrocyte maturation and hypertrophy. Overexpression of Runx2
      stimulated reporter gene expression approximately 7-fold over control in SW1353
      human chondrosarcoma cells and approximately 5-fold over control in primary
      bovine articular chondrocytes, suggesting ADAMTS-5 to be a potential downstream
      target of Runx2. 5'-deletions in the promoter resulted in a substantial loss in
      responsiveness to Runx2 implicating the functional importance of the distal
      promoter region that harbors putative Runx binding elements for achieving maximal
      Runx2 effects. The promoter-reporter construct could serve as a useful tool to
      understand the regulation of ADAMTS-5 gene expression at the transcriptional
      level.

PMID- 17211520
TI  - Fusion of H4/D10S170 to PDGFRbeta in a patient with chronic myelomonocytic
      leukemia and long-term responsiveness to imatinib.

PMID- 17211521
TI  - Folate levels in cancer: a vitamin for a new challenge.

PMID- 17211522
TI  - Sagittal balance of the pelvis-spine complex and lumbar degenerative diseases. A
      comparative study about 85 cases.
AB  - Retrospective analysis of the spino-pelvic alignment in a population of 85
      patients with a lumbar degenerative disease. Several previous publications
      reported the analysis of spino-pelvic alignment in the normal and low back pain
      population. Data suggested that patients with lumbar diseases have variations of
      sagittal alignment such as less distal lordosis, more proximal lumbar lordosis
      and a more vertical sacrum. Nevertheless most of these variations have been
      reported without reference to the pelvis shape which is well-known to strongly
      influence spino-pelvic alignment. The objective of this study was to analyse
      spino-pelvic parameters, including pelvis shape, in a population of 85 patients
      with a lumbar degenerative disease and compare these patients with a control
      group of normal volunteers. We analysed three different lumbar degenerative
      diseases: disc herniation (DH), n = 25; degenerative disc disease (DDD), n = 32;
      degenerative spondylolisthesis (DSPL), n = 28. Spino-pelvic alignment was
      analysed pre-operatively on full spine radiographs. Spino-pelvic parameters were
      measured as following: pelvic incidence, sacral slope, pelvic tilt, lumbar
      lordosis, thoracic kyphosis, spino-sacral angle and positioning of C7 plumb line.
      For each group of patients the sagittal profile was compared with a control
      population of 154 asymptomatic adults that was the subject of a previous study.
      In order to understand variations of spino-pelvic parameters in the patients'
      population a stratification (matching) according to the pelvic incidence was done
      between the control group and each group of patients. Concerning first the pelvis
      shape, patients with DH and those with DDD demonstrated to have a mean pelvic
      incidence equal to 49.8 degrees and 51.6 degrees, respectively, versus 52 degrees
      for the control group (no significant difference). Only young patients, less than
      45 years old, with a disc disease (DH or DDD) demonstrated to have a pelvic
      incidence significantly lower (48.3 degrees) than the control group, P < 0.05. On
      the contrary, in the DSPL group the pelvic incidence was significantly greater
      (60 degrees) than the control group (52 degrees), P < 0.0005. Secondly the three
      groups of patients were characterized by significant variations in spino-pelvic
      alignment: anterior translation of the C7 plumb line (P < 0.005 for DH, P < 0.05
      for DDD and P < 0.05 for DSPL); loss of lumbar lordosis after matching according
      to pelvic incidence (P < 0.0005 for DH, DDD and DSPL); decrease of sacral slope
      after matching according to pelvic incidence (P = 0.001 for DH, P < 0.0005 for
      DDD and P < 0.0005 for DSPL). Measurement of the pelvic incidence and matching
      according to this parameter between each group of patients and the control group
      permitted to understand variations of spino-pelvic parameters in a population of
      patients.

PMID- 17211523
TI  - A functional SNP in ITIH3 is associated with susceptibility to myocardial
      infarction.
AB  - Myocardial infarction (MI) results from complex interactions of multiple genetic
      and environmental factors. To disclose genetic backgrounds of MI, we performed a
      large-scale, case-control association study using 52,608 gene-based single
      nucleotide polymorphism (SNP) markers, and identified a candidate SNP located on
      chromosome 3p21.2-p21.1. Subsequent linkage-disequilibrium mapping indicated very
      significant association between MI and a SNP in exon 2 of the inter-alpha
      (globulin) inhibitor 3 gene (ITIH3; chi(2) = 24.88, P = 6.1 x 10(-7), 3,353
      affected individuals versus 3,807 controls). In vitro functional analyses showed
      that this SNP enhanced the transcriptional level of the ITIH3 gene. Furthermore,
      we found expression of the ITIH3 protein in the vascular smooth muscle cells and
      macrophages in the human atherosclerotic lesions, suggesting ITIH3 SNP to be a
      novel genetic risk factor of MI.

PMID- 17211524
TI  - Mutations of KCNJ2 gene associated with Andersen-Tawil syndrome in Korean
      families.
AB  - Mutations of the KCNJ2 gene are a major underlying cause of Andersen-Tawil
      syndrome (ATS), a rare autosomal dominant inherited disorder that is
      characterized by periodic paralysis, cardiac arrhythmias, and developmental
      dysmorphic features. The KCNJ2 gene encodes an inward rectifying K(+) channel
      protein, Kir2.1, which plays an important role in maintaining the homeostasis of
      channel current in various cell types. We have identified two missense mutations
      of KCNJ2 (R218Q and M307I) in two Korean families diagnosed with ATS. The M307I
      mutation is a novel mutation, located at the intracellular C-terminal domain,
      which is known to be concerned with putative phosphatidylinositol 4,5
      bisphosphate (PIP(2)) binding and channel trafficking.

PMID- 17211525
TI  - Prevalence of lower urinary tract symptoms among female elementary school
      teachers in Taipei.
AB  - The aim of this study was to estimate the prevalence of lower urinary tract
      symptoms (LUTS) among female elementary school teachers in Taipei. A total of 520
      self-administered surveys were distributed to 26 elementary schools in Taipei
      City. Data analyses were based on 445 usable surveys. The prevalence rates for
      different types of LUTS ranged from 9.9 to 44.5%. The prevalence of urinary
      incontinence (UI; 26.7%) and nocturia (16.0%) fell within the prevalence
      estimates of these LUTS in North American and European women. Employed women in
      this study were more likely to experience LUTS than women in previous
      epidemiological or community studies. This study extended research on UI into
      other LUTS among employed women in Asia. Study results suggest that the working
      environment may affect LUTS in female elementary school teachers. This
      preliminary study is important for developing future behavioral interventions for
      female LUTS in the workplace.

PMID- 17211526
TI  - Prevalence and risk factors for pelvic floor symptoms in women in rural El
      Salvador.
AB  - Our aim was to assess the frequency of pelvic floor symptoms among women in rural
      El Salvador. After written informed consent was obtained, we administered the
      short form of the urodynamic distress inventory (UDI-6) plus four other pelvic
      floor questions to 236 women aged 30 to 75 in rural El Salvador attending a
      general medicine or gynecology clinic. Average (SD) age, parity, and body mass
      index were 48.0 (8.4) years, 5.9 (3.4), and 26.9 (4.9) kg/m(2), respectively. Ten
      (4.2%) women had a prior hysterectomy, 16 (6.8%) women were smokers, and 108
      (45.8%) women were postmenopausal. Seventy-one percent of women reported urinary
      incontinence (UI); 49.3 and 61.1% of women reported urge UI and stress UI,
      respectively. Forty-one percent of women reported fecal incontinence (FI) of
      solid or liquid stool. Women with UI were significantly more likely to have had a
      hysterectomy compared to women without UI. Women with FI had significantly fewer
      years of education when compared to women without FI. In conclusion, pelvic floor
      symptoms are highly prevalent among women in rural El Salvador.

PMID- 17211527
TI  - Factors associated with anal sphincter laceration in 40,923 primiparous women.
AB  - The objective of this study was to identify factors associated with anal
      sphincter laceration in primiparous women. A subpopulation of 40,923 primiparous
      women at term with complete data sets was abstracted from a state-wide perinatal
      database in Germany. Outcome variable was anal sphincter laceration. Independent
      variables were 17 known obstetrical risk factors/conditions/interventions
      impacting childbirth recorded on the perinatal data collection sheet. Cross table
      analysis followed by logistic regression analysis was used for data analysis.
      Logistic regression showed episiotomy (OR, 3.23; CI, 2.73-3.80) and forceps
      delivery (OR, 2.68, CI, 2.17-3.33) to be most strongly associated with anal
      sphincter laceration. Women with a BMI >or= 30 kg/m2, and smokers had a
      significantly lower risk of anal sphincter laceration. Local, pudendal, and
      epidural analgesia all reduced the risk of anal sphincter laceration. Iatrogenic
      factors most strongly associated with anal sphincter laceration in primiparous
      women include routine episiotomy and forceps delivery.

PMID- 17211528
TI  - Comparison of the efficacy and tolerability of solifenacin succinate with or
      without previous use of trospium chloride.
AB  - Overactive bladder syndrome (OBS) is described as urinary urgency with or without
      incontinence, usually with increased daytime frequency and nocturia in the
      absence of another identifiable pathological process. Nowadays and despite other
      alternative therapies, the mainstay of OBS is still the pharmacological approach,
      mainly with anti-muscarinic drugs. To compare the efficacy of a 30-day
      solifenacin succinate (5 mg OD) treatment with or without previous medication
      with trospium chloride, a prostective open, two-arm, parallel group study was
      conducted for 5 weeks in 40 patients with OBS. The primary endpoint was patient
      self-assessment of improvement after 30 days of medication. Secondary endpoints
      included the reduction of the daily number of voids and urgency or involuntary
      leakage episodes. Adverse reactions and therapeutic stoppage were also evaluated.
      To be included in the trospium chloride treatment group, patients were required
      to have been treated with such drug for 1 to 6 months before the present study.
      Evaluation and efficacy assessment were accomplished using a 3-day bladder diary
      and an urgency severity scale (USS). Safety assessment was done by recording all
      the patients' complaints after starting medication. A total of 40 patients were
      enrolled for this study, 19 without previous medication and 21 who had already
      tried trospium chloride. Two patients from the non-previous medication group were
      excluded. Globally, there was a statistically significant reduction for the USS
      (2.73-->1.73), the daily number of voids (9.5-->7.0), of urgency episodes (9.1-
      >4.0) and of involuntary leakage episodes (3.6-->1.0) over the 24 h. Six patients
      had no improvement, four from the previous trospium chloride group and two from
      the non-previous medication group. Three patients reported side effects, two
      cases of dry mouth and one case of constipation. One patient dropped out of the
      treatment due to an unspecified intolerance. Solifenacin succinate 5 mg seems to
      be effective concerning patients' self-assessment of improvement and decrease in
      the mean number of daily voids, urgency episodes and incontinence episodes. This
      was reported both in patients who have already been medicated with trospium
      chloride and those who have never taken any kind of medication. Regarding side
      effects, solifenacin is quite well-tolerated in both groups.

PMID- 17211529
TI  - Long-lasting bioresorbable poly(lactic acid) (PLA94) mesh: a new approach for
      soft tissue reinforcement based on an experimental pilot study.
AB  - The purpose of this study was to evaluate host response and soft-tissue
      regeneration after poly(lactic acid) (PLA) mesh implantation in a rat model, in
      comparison with light-weight polypropylene (PPL) and poly(glycolic acid) (PGA)
      meshes. Full-thickness abdominal wall defects were created in 45 Wistar rats and
      reconstructed with 15 PLA(94), 15 PPL and 15 PGA meshes. Animals were killed on
      days 7, 30 and 90 to evaluate the presence of adhesions and changes in tensile
      strength of the implants. Histopathology and immunohistochemistry were performed
      to evaluate the collagen deposition and the inflammatory response. Statistics
      were done using unpaired Student's t-test, Mann-Whitney rank sum test, Student
      Newman-Keuls test and Bonferroni (Dunn) t-test. The inflammatory response induced
      by the PLA mesh implantation was significantly milder than after PPL mesh. In
      PLA, vascularity and collagen organization was significantly higher than in PPL
      and PGA at 30 and 90 days, and collagen composition score was significantly
      higher than in PPL at 7 and 30 days. In PLA, shrinkage was significantly lower
      than in PPL and PGA at 7 and 30 days. Elongation at break and tensile strength
      were comparable between PLA and PPL over the 90-day period. The PLA mesh induces
      a milder inflammatory response, more orderly collagen deposition than PPL, and
      preserved comparable tensile strength after 90 days.

PMID- 17211530
TI  - The reduction of physical activity reflects on the bone mass among young females:
      a follow-up study of 142 adolescent girls.
AB  - Maintenance of positive effects of physical activity on growing bone is unknown.
      Physical activity was associated with increased BMC and BMD in a 7-year follow-up
      with 142 adolescent girls. Marked reduction in physical activity had an
      unfavorable effect on bone measurements, which is an important finding when the
      prevention of osteoporosis is considered. INTRODUCTION: Environmental factors
      influence quality and durability of bone. Physical activity, with high-impact
      weight bearing activity during puberty in particular, has been shown to have a
      beneficial effect on growing bone. Only few studies have been published on the
      maintenance of these effects. METHODS: At baseline, 142 girls aged 9-15 years
      participated in the present 7-year follow-up study. Growth and development,
      physical activity, and intakes of calcium and vitamin-D were recorded at
      intervals. BMC and BMD measurements were repeated using DXA. Based on the
      recording of physical activity during the follow-up measurements, the effect of
      the reduction in physical activity was examined with the bone measurements, and
      the measurements in the tertiles based on the amount of physical activity during
      the whole follow-up period were compared. RESULTS: Physical activity was
      positively associated with the development of BMC and BMD during the follow-up.
      The mean BMC of the lumbar spine increased 1.69 g (3%) (p = 0.021) more among
      those girls who maintained the physical activity level as compared with those who
      reduced it during last 4 years. In the femoral neck, the corresponding difference
      was 0.14 g (4.6%) (p = 0.015) between the same two groups of girls. The mean
      increases in BMC at lumbar spine and femoral neck were more substantial among
      those girls having the highest physical activity levels during the 7-year follow
      up (46.7% and 22.6%) as compared with those having the lowest physical activity
      levels (43.3% and 17.4%, respectively). CONCLUSIONS: The findings of the present
      study show that regular physical activity is valuable in preserving the peak bone
      mass acquired at puberty in particular. Many of the girls who markedly reduced
      their activity levels lost bone in their femoral neck prior to their 25th
      birthday.

PMID- 17211531
TI  - The association between non-melanoma skin cancer and osteoporotic fractures--a
      population-based record linkage study.
AB  - We studied the association between osteoporotic fractures and prior non-melanoma
      skin cancer (NMSC, a biomarker for cumulative sun exposure). The risk of prior
      NMSC in our fracture cohort was significantly reduced (standardised incidence
      ratio 0.69, 95% CI 0.61, 0.78). Adequate lifetime sun exposure may be necessary
      to protect against osteoporotic fractures in later life. INTRODUCTION: The
      relationship between cumulative sun exposure and osteoporotic fractures is
      uncertain. We aimed to study the association between non-melanoma skin cancer
      (NMSC), a marker of cumulative sun exposure, and osteoporotic fractures in an
      older cohort. METHODS: A retrospective cohort study in southern Tasmania in
      people aged at least 50 years with incident radiographic fracture (n = 2,283) was
      carried out. By record linkage to the Tasmanian Cancer Registry the cohort was
      followed backwards through time until the occurrence of NMSC or end-of follow-up.
      Relative risk was estimated by the standardised incidence ratio (SIR) using sex-,
      age- and calendar year-specific cancer incidence rates in southern Tasmania as
      reference. RESULTS: The incidence of prior NMSC in the fracture cohort was 31%
      lower than for the general population (SIR 0.69, 95% CI 0.61, 0.78). This effect
      was significant for most fracture subtypes except pelvic and wrist fractures and
      observed for both NMSC subtypes, squamous cell carcinoma and basal cell
      carcinoma. CONCLUSIONS: Older people with osteoporotic fractures may have had
      lifestyles linked to lower cumulative sunlight exposure. Achieving a balance
      between adequate lifetime sun exposure and protection against its adverse effects
      (such as fractures and skin cancer) may require assessment of individual risks.

PMID- 17211532
TI  - A simple protocol for preventing falls and fractures in elderly individuals with
      musculoskeletal disease.
AB  - Our protocol resulted in a significant prevention of falls and fractures in
      addition to marked improvements in the balance function. Intervention comprised a
      new balance exercise and quadriceps femoris exercise. Subjects were outpatients
      aged >or=65 years old with musculoskeletal disorders who had a result of <or=15 s
      for the timed one-leg balance test. INTRODUCTION: A study on chronological
      changes in the level of required care revealed that the level of care increases
      markedly for older patients requiring non-intensive or intensive long-term care.
      The aim of the present study was to identify frail elderly patients among older
      patients with chronic pain of the musculoskeletal system and to assess the
      fracture prevention and fall prevention effects of exercise therapy using
      stratified analysis. METHODS: This was a prospective cohort study consisting of
      683 outpatients with chronic pain of the musculoskeletal system who were >or=65
      years old and had a result of <or=15 s for the timed one-leg balance test with
      eyes open. Intervention consisted of a new balance exercise and quadriceps
      femoris exercise regimen. The main outcome was fall rate, while secondary
      outcomes were the results of the timed one-leg balance test with eyes open and
      fracture rate. RESULTS: Fall rate was decreased by 44% (p < 0.001) and fracture
      rate by 47% (p < 0.05) by 8 months after the start of the intervention. The
      results of the timed one-leg balance testing with eyes open improved two- to
      threefold after intervention (p < 0.01). CONCLUSIONS: Our protocol has been
      safely implemented at a large number of clinics in Japan, and the reductions in
      frequency of falls and fractures suggest that it provides effective preventive
      care.

PMID- 17211533
TI  - Down-regulation of PHLDA1 gene expression is associated with breast cancer
      progression.
AB  - In a previous study, using differential display reverse transcriptase-PCR (DDRT
      PCR) we showed that down-regulation of the PHLDA1 (pleckstrin homology-like
      domain, family A, member 1; also named TDAG51) mRNA was down-regulated in breast
      tumors compared with normal breast tissue. The present study was conducted to
      determine the expression pattern and predictive prognostic value of PHLDA1 in
      breast cancer. A series of 720 primary invasive breast tumors were examined for
      PHLDA1 expression. PHLDA1 mRNA expression was determined in 74 breast tumors
      using quantitative Real Time PCR analysis (qPCR). PHLDA1 protein expression was
      evaluated by immunohistochemistry (IHC) using Tissue Microarrays (TMA) containing
      699 primary invasive breast tumors. Reduced PHLDA1 mRNA expression was identified
      in 72% (53/74) of the primary breast tumors analyzed. Seventy-three percent
      (512/699) of cases analyzed showed negative PHLDA1 protein expression. Down
      regulation of PHLDA1 protein was a strong predictor of poor prognosis for breast
      cancer patients. Breast cancer patients with tumors that were negative for PHLDA1
      protein expression had shorter disease free survival (P < 0.001) and overall
      survival (P < 0.001) than patients with tumors that were positive for PHLDA1
      protein expression. In addition patients with tumors exhibiting reduced PHLDA1
      expression and paucity for ER had the worse outcome (P < 0.001). Multivariate
      analysis indicated that PHLDA1 protein expression is an independent prognostic
      factor of patient survival. To our knowledge, the expression pattern of PHLDA1 in
      breast cancer has not previously been investigated. Our results provide strong
      evidence that reduced PHLDA1 expression is important in breast cancer progression
      and could serve as useful prognostic marker of disease outcome.

PMID- 17211534
TI  - Body mass index and HER-2 overexpression in breast cancer patients over 50 years
      of age.
AB  - PURPOSE: In breast cancer, in vitro as well as in vivo experiments have shown an
      inverse relationship between HER-2 and steroid hormone receptors. It is unknown
      whether circulating estrogens affect HER-2 expression. We hypothesize that the
      postmenopausal body mass index (BMI) as a surrogate marker for bio-available
      estrogens, is inversely associated with HER-2 over-expression. PATIENTS AND
      METHODS: A total of 535 women over age 50 or with known postmenopausal status,
      with a unilateral, not previously treated, operable breast cancer were evaluated
      the evening prior to surgery for body weight, height, abdominal and hip
      circumference over a 3 years period. Waist-to-hip ratio (WHR) and BMI were
      calculated. HER-2, estrogen receptor and progesterone receptor staining was done
      by immunohistochemistry. All tumours with DAKO 2+ staining were submitted for HER
      2 detection by FISH analysis. HER-2 was defined as positive if DAKO 3+ or FISH
      positive. We assessed the frequency of HER-2 positivity in each of 6 quantiles
      for all parameters of body composition and tested for a trend in HER-2 expression
      across the 6 quantiles. Furthermore, we investigated whether BMI contributed,
      together with other known predictors for HER-2, in a standard multivariate
      logistic regression model that predicts HER-2 over-expression. RESULTS: There is
      a decrease in HER-2 over-expression per increasing quantile of BMI. In a
      multivariate model-including both steroid receptors-BMI remains an independent
      predictor for HER-2 over-expression. CONCLUSION: In women over age 50 or with
      known postmenopausal status with an operable breast cancer, there is an inverse
      association between BMI and HER-2 over-expression.

PMID- 17211535
TI  - Aromatase inhibitors and cardiac toxicity: getting to the heart of the matter.
AB  - Recent advances in breast cancer treatment include the advent of aromatase
      inhibitors (AIs) in the adjuvant setting with better efficacy and toxicity
      profiles than tamoxifen. However, AIs generally do not improve lipid profile as
      tamoxifen does, and there has been suggestion of increased cardiovascular risk
      with AI use. This has become an area of concern, particularly in light of the
      view that tamoxifen may protect against cardiovascular disease. This review of
      the current literature and updated trial data examines the effect both AIs and
      tamoxifen have on lipids and cardiovascular risk. It also highlights the
      importance of interpreting such data within the larger context of cardiovascular
      health in postmenopausal women.

PMID- 17211536
TI  - Impact of a programme of mass mammography screening for breast cancer on socio
      economic variation in survival: a population-based study.
AB  - BACKGROUND: After a systematic mass mammography breast cancer screening programme
      was implemented between 1991 and 1996 (attendance 80%), we evaluated its impact
      on survival according to socioeconomic status (SES). METHODS: We studied survival
      rates up to 1-1-2005 for all consecutive breast cancer patients aged 50-69 and
      diagnosed in the period 1983-2002 in the area of the Eindhoven Cancer Registry (n
      = 4939). Multivariate analyses were performed using Cox regression analysis.
      RESULTS: The proportion of breast cancer patients with a low SES decreased from
      22% in 1983-1990 to 14% in 1997-2002 when attendance was 85%. The proportion of
      newly diagnosed patients with stage III or IV disease in 1997-2002 was only 10%
      compared to 14% in 1991-1996 and 26% in 1983-1989 (P < 0.0001). Stage
      distribution improved for all socio-economic groups (P = 0.01). Survival was
      similar for all socio-economic groups in 1983-1990, but after the introduction of
      the screening programme women with low SES had lower age- and stage-adjusted
      survival rates (HR 2.0, 95%CI: 1.3-3.0). Survival was better for patients
      diagnosed in 1997-2002 compared to 1983-1990 for all socioeconomic strata; it was
      substantially better for the high SES group (HR 0.36, 0.2-0.5) compared to the
      lowest SES (HR 0.77, 0.6-1.1). CONCLUSION: Although survival improved for women
      from each of the socio-economic strata, related to the high participation rate of
      the screening programme, women from lower socio-economic strata clearly benefited
      less from the breast cancer screening programme. That is also related to the
      higher prevalence of comorbidity and possibly suboptimal treatment.

PMID- 17211537
TI  - Routine mobilization of the splenic flexure is not necessary during anterior
      resection for rectal cancer.
AB  - PURPOSE: Splenic flexure mobilization is widely considered to be an essential
      component of anterior resection for rectal cancer. It was our hypothesis that
      selective splenic flexure mobilization would reduce operative times without
      increasing morbidity or affecting cure. METHODS: A total of 100 consecutive
      patients with rectal cancer (mean 8 (range, 4-15) cm from anal verge) who
      underwent anterior resection for cure between 1996 and 2002 had splenic flexure
      mobilization only as required to achieve a tension-free anastomosis. Operative
      time, postoperative morbidity, pathologic findings, and recurrence rates were
      recorded. RESULTS: There were no clinicopathologic differences between those who
      had splenic flexure mobilization (n = 26) and those who did not (n = 74). Mean
      operative time in the splenic flexure mobilization group was longer, 167 (range,
      130-200) minutes vs. 120 (range, 95-180) minutes in the nonmobilized group (P =
      0.023). Mean length of specimen resected was longer in the splenic flexure
      mobilization group: 36 vs. 18 cm (P = 0.008). Anastomotic complications (4
      percent), local recurrence (7 percent, median follow-up, 38 months),
      perioperative morbidity (32 percent) and mortality (2 percent), and survival did
      not differ between the two groups. CONCLUSIONS: Routine splenic flexure
      mobilization is not required for safe anterior resection in patients with rectal
      cancer. Avoiding splenic flexure mobilization results in shorter operative times
      and does not increase postoperative morbidity, anastomotic leakage, or local
      recurrence.

PMID- 17211538
TI  - Biogenic black crusts on buildings in unpolluted environments.
AB  - Samples of peeling black crusts from modern and historic buildings in Campeche,
      Mexico, from a gravestone on the island of Dom Khon, Lao, and from the Anglican
      cathedral in Belize City were analyzed microbiologically, by scanning electron
      microscopy plus electron dispersive spectroscopy (EDS) and for pigment
      composition. In all cases, the surface was covered by a thick mat of
      cyanobacteria with dark brown sheaths. These were filamentous organisms of the
      genera Scytonema or Fischerella/Mastigocladus, except for one sample, where
      coccoid cyanobacteria of Subsection II were predominant. Fungi were not present
      at all sites and, where seen, were not the major biomass. High
      scytonemin:chlorophyll a ratios correlated with the dark pigmentation of the
      cyanobacterial cells and indicated the stressful conditions under which these
      organisms were living (high temperatures and ultraviolet levels, frequent
      desiccation). The absence, or low levels, of sulfur in the biofilms confirmed
      that there was little urban pollution at the sites and the EDS analysis showed
      that the black coloration was caused solely by cell pigmentation; no dark-colored
      elements were present at high concentrations. These results demonstrate that,
      unlike chemically formed thick black crusts found in polluted atmospheres, thin
      black crusts (which could be called patinas) in clean environments may be
      predominantly composed of filamentous cyanobacteria.

PMID- 17211539
TI  - Porin isolated from the outer membrane of Erwinia amylovora and its encoding
      gene.
AB  - A major Erwinia amylovora outer-membrane protein (Omp-EA) and the gene encoding
      for this protein (omp-EA) were isolated and characterized. The native Omp-EA
      protein forms a trimeric structure of approximately 114 kDa. This protein
      demonstrated high resistance to detergents such as SDS and octyl-glucopyranoside,
      but disaggregated to monomers with a molecular weight (MW) of approximately 39
      kDa after heating at 95 degrees C for 10 minutes in sample buffer. The pore
      forming ability of the oligomeric Omp-EA was determined by the liposome swelling
      assay, demonstrating that the oligomeric protein formed nonspecific channels with
      an exclusion limit of approximately 660 Da. On dissociation, the monomers did not
      exhibit pore-forming ability. The omp-EA gene was cloned and sequenced (GenBank
      Accession No. DQ184680). Sequence analysis revealed an open reading frame of 1152
      bases. The deduced amino-acid sequence had 383 amino acids. The mature protein
      consisted of 362 amino acids and had a calculated MW of 39,210 Da. Multiple
      sequence alignment of Omp-EA with other porins from the Enterobacteriaceae family
      revealed 51% to 63% identity. The first 16 amino acids from the N-terminal
      exhibited the highest identity (100%) to the porins OmpC, OmpF, and PhoE of
      Escherichia coli. Two methods were used to predict the secondary structure:
      APSSP2 and Hidden and Markov's model. The monomers of Omp-EA porin presented a
      topology of 16 transmembranal beta-strands. The area of the loops between the
      beta -strands was proposed. It is suggested that further research on the porin
      and its loops may be important for understanding the mechanism of E. amylovor to
      invade plant tissues.

PMID- 17211540
TI  - Biosurfactant production by antarctic facultative anaerobe Pantoea sp. during
      growth on hydrocarbons.
AB  - The facultative anaerobe Pantoea sp. strain A-13, isolated from ornithogenic soil
      of Dewart Island (Frazier Islands), Antarctica, produced glycolipid
      biosurfactants when grown on n-paraffins or kerosene as the sole source of carbon
      and energy. Hemolysis of erythrocytes, growth inhibition of Bacillus subtilis,
      and thin-layer chromatography studies have suggested that the secreted
      glycolipids are rhamnolipids. Glycolipids produced by kerosene-grown cells
      decreased the surface tension at the air-water interface to 30 mN/m and possessed
      a low critical micelle concentration value of 40 mg/l, which indicated high
      surface activity. They efficiently emulsified aromatic hydrocarbons, kerosene,
      and n-paraffins. Biosurfactant production contributed to an increase in cell
      hydrophobicity, which correlated with increased growth of the strain on tested
      hydrocarbons. According to the results, the Antarctic biosurfactant-producing
      strain Pantoea sp. A-13 appears to be valuable source for application in
      accelerated environmental bioremediation.

PMID- 17211541
TI  - Cytoprotective agent in Lactobacillus bulgaricus extracts.
AB  - Adenosine 5'-diphosphoribose (ADP-ribose) has been identified as a significant
      contributor to the anti-cytotoxic activity of Lactobacillus bulgaricus extracts.
      Although the biological activities associated with the administration of
      probiotic bacteria and components thereof are sometimes attributed to the
      peptidoglycans that comprise a substantial portion of the Gram-positive bacterial
      cell wall, we found that the beta-nicotine adenine dinucleotide (NAD) hydrolysis
      product ADP-ribose was a significant contributor to the observed anti
      cytotoxicity in our L. bulgaricus extracts. The ADP-ribose was isolated,
      identified, and quantitated by high performance liquid chromatography (HPLC) and
      by nuclear magnetic resonance (NMR) spectroscopy. ADP-ribose levels as low as 5
      mg/L exhibited a measurable inhibition of tumor necrosis factor alpha (TNF-alpha)
      mediated cytotoxicity in an in vitro cell assay, whereas the ADP-ribose content
      of the L. bulgaricus extracts often exceeded 5 mg/g dry weight.

PMID- 17211542
TI  - Absence of classical heat shock response in the citrus pathogen Xylella
      fastidiosa.
AB  - The fastidious bacterium Xylella fastidiosa is associated with important crop
      diseases worldwide. We have recently shown that X. fastidiosa is a peculiar
      organism having unusually low values of gene codon bias throughout its genome
      and, unexpectedly, in the group of the most abundant proteins. Here, we
      hypothesized that the lack of codon usage optimization in X. fastidiosa would
      incapacitate this organism to undergo quick and massive changes in protein
      expression as occurs in a classical stress response. Proteomic analysis of the
      response to heat stress in X. fastidiosa revealed that no changes in protein
      expression can be detected. Moreover, stress-inducible proteins identified in the
      closely related citrus pathogen Xanthomonas axonopodis pv citri were found to be
      constitutively expressed in X. fastidiosa. These proteins have extremely high
      codon bias values in the X. citri and other well-studied organisms, but low
      values in X. fastidiosa. Because biased codon usage is well known to correlate to
      the rate of protein synthesis, we speculate that the peculiar codon bias
      distribution in X. fastidiosa is related to the absence of a classical stress
      response, and, probably, alternative strategies for survival of X. fastidiosa
      under stressfull conditions.

PMID- 17211543
TI  - Occurrence of strains producing specific antibacterial inhibitory agents in five
      genera of Enterobacteriaceae.
AB  - Striking differences in the production of specific inhibitory agents affecting
      other strains of the same (or of related) species were found between genera of
      the family Enterobacteriaceae. We tested 50-163 strains each of the potentially
      pathogenic genera: Escherichia, Citrobacter, Enterobacter, Kluyvera, and
      Leclercia for their ability to produce bacteriophages, high-molecular-weight
      (HMW) and low-molecular-weight (LMW) bacteriocins and siderophores against the
      same sets of strains, using the cross-test method. The genus Escherichia differs
      substantially from all other Enterobacteriaceae, harboring a notable proportion
      of lysogenic (36.6%) and colicinogenic (13.9%) strains. Only 18.2% of the
      Citrobacter strains are lysogenic and only rarely are they colicinogenic,
      although in 7.3%, they produce phage tail-like bacteriocins. On the other hand,
      Kluyvera strains were only in 1.8% lysogenic, no colicinogenic strains were
      found, but in 7.3%, they produced siderophores causing zones of growth inhibition
      in agar cultures of strains of the same genus. In Leclercia, 10.0% of the strains
      were lysogenic, 2.0% produced HMW bacteriocins, no colicinogenic strains were
      found and 2.0% produced siderophores. Enterobacter has shown 23.1% of strains
      producing siderophores, whereas merely 7.7% were lysogenic, 1.9% colicinogenic
      and 3.8% formed phage tail-like bacteriocins. HMW bacteriocins of Enterobacter
      strains disposed of an unusually wide spectrum of activity. The siderophore
      activity spectrum was rather wide in any genus, but the siderophores were usually
      not produced by strains producing phages or colicins.

PMID- 17211544
TI  - Purification and characterization of a 4-hydroxybenzoate decarboxylase from
      Chlamydophila pneumoniae AR39.
AB  - Chlamydophila pneumoniae AR39 is an obligate intracellular pathogen that causes
      human acute and chronic respiratory tract diseases. One protein from C.
      pneumoniae AR39 was assigned as 4-hydroxybenzoate decarboxylase (HBDC). Assays
      done with the purified oxygen-sensitive protein showed that the optimum pH and
      temperature were 7.5 and 30 degrees C, respectively. The Km and Vmax obtained for
      4-hydroxybenzoate were approximately 0.21 mM and 11.9 nM min(-1) mg(-1),
      respectively. During the period of 4-hydroxybenzoate decarboxylation, overall
      activity of the thermal-sensitive protein was 5.06 nM min(-1) mg(-1) protein. The
      4-hydroxybenzoate decarboxylation was promoted by Mg(2+), Fe(2+), Mn(2+), and
      Ca(2+) but not by Cu(2+) or Zn(2+). The enzyme also slowly catalyzed the reverse
      reaction, which was phenol carboxylation.

PMID- 17211545
TI  - Repeated-batch xylitol bioproduction using yeast cells entrapped in polyvinyl
      alcohol-hydrogel.
AB  - Xylose-to-xylitol conversion was investigated in a bench-scale bioreactor using
      Candida guilliermondii cells entrapped within polyvinyl alcohol-hydrogel beads in
      a system operated in repeated-batch mode with cell recycling. Yeast-viable cells
      were immobilized in the support using the freezing-thawing method. Bioconversion
      assays were performed in a stirred tank reactor operated at 400-rpm agitation
      speed, 30 degrees C temperature, and 1.04-vvm air flow rate. The system was
      explored during six successive cycles, and a small decrease in the conversion
      performance in the fifth cycle was observed, but the biocatalytic activity of the
      microorganism was recovered in the sixth cycle after washing the particles.
      During the process, the hydrogel beads maintained their shape and size without
      appreciable deterioration. Xylitol production, yield factor, and volumetric
      productivity increased with progressive recycling of cells and achieved their
      maximum values (P(F) = 39.7 g l(-1); Y(P/S) = 0.77 g g(-1); Q(P) = 0.53 g l(-1)
      h(-1), respectively) after the third cell recycling, probably because of cells'
      adaptation to the medium.

PMID- 17211546
TI  - Bactericidal monoclonal antibody against Moraxella catarrhalis
      lipooligosaccharide cross-reacts with Haemophilus Spp.
AB  - Monoclonal antibodies (MAbs) against lipooligosaccharide (LOS) determinants after
      immunization of BALB/c mice with heat inactivated Moraxella catarrhalis serotype
      A were generated. MAb 219A9 was specific for a common epitope of A, B, and C M.
      catarrhalis serotypes in ELISA and immunofluorescent test (IFT). In both tests it
      also cross-reacted with whole bacteria and LPS antigens isolated from non
      typeable H. influenzae and H. parainfluenzae strains. IgM antibody clone 219A9
      possessed a strong bactericidal effect against the three serotypes in the
      presence of complement. Our results demonstrate that antibodies directed to a
      single LOS epitope common for A, B, and C serotype could be highly protective.
      This suggests that the common determinants are very promising in the development
      of LOS-based vaccine against M. catarrhalis. The cross-reactions of MAb 219A9
      with Haemophilus spp. also show that immunization could result in immune response
      to epitopes conserved in other important respiratory pathogens.

PMID- 17211548
TI  - Experimental evolution of gene duplicates in a bacterial plasmid model.
AB  - The fate of gene duplicates subjected to diversifying selection was tested
      experimentally in a bacterial system. The wild-type TEM-1 beta-lactamase gene
      confers resistance to ampicillin but not to cefotaxime. Point mutations confer
      cefotaxime resistance, but they compromise ampicillin resistance. Thus, selection
      for both drug resistances in a bacterium with two copies of beta-lactamase should
      favor the divergence of one copy to improve cefotaxime resistance while
      maintaining the other copy to preserve ampicillin resistance. This selection was
      performed on a bacterium with identical sequences of beta-lactamase on two
      separate, compatible plasmids. As expected, one plasmid evolved increased
      cefotaxime resistance when appropriately strong cefotaxime selection was applied.
      However, the cefotaxime-resistant plasmid maintained sufficient ampicillin
      resistance to tolerate the concentration of ampicillin used, and the other
      plasmid was lost. Hosts carrying both the cefotaxime-resistant and wild-type
      plasmids were then subjected to various higher concentrations of both drugs to
      find conditions that would ensure the maintenance of both plasmids. In a striking
      contradiction to our model, no such conditions were found. The fitness cost of
      carrying both plasmids increased dramatically as antibiotic levels were raised,
      and either the wild-type plasmid was lost or the cells did not grow. This study
      highlights the importance of the cost of duplicate genes and the quantitative
      nature of the tradeoff in the evolution of gene duplication through functional
      divergence.

PMID- 17211547
TI  - Retrotransposons and tandem repeat sequences in the nuclear genomes of
      cryptomonad algae.
AB  - The cryptomonads are an enigmatic group of unicellular eukaryotic algae that
      possess two nuclear genomes, having acquired photosynthesis by the uptake and
      retention of a eukaryotic algal endosymbiont. The endosymbiont nuclear genome, or
      nucleomorph, of the cryptomonad Guillardia theta has been completely sequenced:
      at only 551 kilobases (kb) and with a gene density of approximately 1 gene/kb, it
      is a model of compaction. In contrast, very little is known about the structure
      and composition of the cryptomonad host nuclear genome. Here we present the
      results of two small-scale sequencing surveys of fosmid clone libraries from two
      distantly related cryptomonads, Rhodomonas salina CCMP1319 and Cryptomonas
      paramecium CCAP977/2A, corresponding to approximately 150 and approximately 235
      kb of sequence, respectively. Very few of the random end sequences determined in
      this study show similarity to known genes in other eukaryotes, underscoring the
      considerable evolutionary distance between the cryptomonads and other eukaryotes
      whose nuclear genomes have been completely sequenced. Using a combination of
      fosmid clone end-sequencing, Southern hybridizations, and PCR, we demonstrate
      that Ty3-gypsy long-terminal repeat (LTR) retrotransposons and tandem repeat
      sequences are a prominent feature of the nuclear genomes of both organisms. The
      complete sequence of a 30.9-kb genomic fragment from R. salina was found to
      contain a full-length Ty3-gypsy element with near-identical LTRs and a
      chromodomain, a protein module suggested to mediate the site-specific integration
      of the retrotransposon. The discovery of chromodomain-containing retroelements in
      cryptomonads further expands the known distribution of the so-called
      chromoviruses across the tree of eukaryotes.

PMID- 17211549
TI  - Mitochondrial genome of Savalia savaglia (Cnidaria, Hexacorallia) and early
      metazoan phylogeny.
AB  - Mitochondrial genomes have recently become widely used in animal phylogeny,
      mainly to infer the relationships between vertebrates and other bilaterians.
      However, only 11 of 723 complete mitochondrial genomes available in the public
      databases are of early metazoans, including cnidarians (Anthozoa, mainly
      Scleractinia) and sponges. Although some cnidarians (Medusozoa) are known to
      possess atypical linear mitochondrial DNA, the anthozoan mitochondrial genome is
      circular and its organization is similar to that of other metazoans. Because the
      phylogenetic relationships among Anthozoa as well as their relation to other
      early metazoans still need to be clarified, we tested whether sequencing the
      complete mitochondrial genome of Savalia savaglia, an anthozoan belonging to the
      order Zoantharia (=Zoanthidea), could be useful to infer such relationships.
      Compared to other anthozoans, S. savaglia's genome is unusually long (20,766 bp)
      due to the presence of several noncoding intergenic regions (3691 bp). The genome
      contains all 13 protein coding genes commonly found in metazoans, but like other
      Anthozoa it lacks most of the tRNAs. Phylogenetic analyses of S. savaglia
      mitochondrial sequences show Zoantharia branching closely to other Hexacorallia,
      either as a sister group to Actiniaria or as a sister group to Actiniaria and
      Scleractinia. The close relationships suggested between Zoantharia and Actiniaria
      are reinforced by strong similarities in their gene order and the presence of
      similar introns in the COI and ND5 genes. Our study suggests that mitochondrial
      genomes can be a source of potentially valuable information on the phylogeny of
      Hexacorallia and may provide new insights into the evolution of early metazoans.

PMID- 17211552
TI  - Hypotension and cognitive defects.

PMID- 17211551
TI  - A phylogeographic split in Buxus balearica (Buxaceae) as evidenced by nuclear
      ribosomal markers: when ITS paralogues are welcome.
AB  - Sequences from the ribosomal nuclear internal transcribed spacers (ITS) have been
      widely used to infer evolutionary hypotheses across a broad range of living
      organisms. Intraspecific sequence variation is assumed to be absent or negliable
      in most species, but few detailed studies have been conducted to assess the
      apportionment of ITS sequence variation within and between plant populations.
      Buxus balearica was chosen as a model species to assess the levels of
      infraspecific and intragenomic ITS variation in rare and endangered species
      occurring in disjunct populations around the Mediterranean basin. Intragenomic
      polymorphic sites were detected for western and eastern accessions of B.
      balearica and in two accessions of the sister species B. sempervirens. Overall,
      19 different ribotypes were found in B. balearica after sequencing 48 clones,
      whereas 15 ribotypes were detected in 19 clones of B. sempervirens. The integrity
      and secondary structure stability of the ribosomal sequences suggest that they
      are not pseudogenes. The high number of ribotypes recovered through cloning
      suggested that some sequences could be chimeric or generated in vivo by partial
      homogenization through gene conversion or unequal crossing-over. Average sequence
      divergence among B. balearica clones was 0.768%, and the most divergent sequences
      differed by 1.62%. Available evidence does not suggest that B. balearica
      paralogues have been obtained from other extant Buxus species through
      interspecific hybridization. The presence of several ribosomal sequences in box
      implies that the molecular forces driving the concerted evolution of this
      multigene family are not fully operational in this genus. Phylogenetic analyses
      of cloned ITS sequences from B. balearica displayed very poor resolution and only
      two clades received moderate bootstrap support. Despite the marked intragenomic
      sequence divergence found, ribosomal data suggest a clear phylogeographic split
      in B. balearica between western and eastern accessions. The distinct, nonchimeric
      sequences that are postulated as being present in each biogeographic group
      suggest that box populations from Anatolia (eastern Mediterranean) are relict.

PMID- 17211550
TI  - Looking for organization patterns of highly expressed genes: purine-pyrimidine
      composition of precursor mRNAs.
AB  - We analyzed precursor messenger RNAs (pre-mRNAs) of 12 eukaryotic species. In
      each species, three groups of highly expressed genes, ribosomal proteins, heat
      shock proteins, and amino-acyl tRNA synthetases, were compared with a control
      group (randomly selected genes). The purine-pyrimidine (R-Y) composition of pre
      mRNAs of the three targeted gene groups proved to differ significantly from the
      control. The exons of the three groups tested have higher purine contents and R
      tract abundance and lower abundance of Y-tracts compared to the control (R-tract
      tract of sequential purines with Rn>or=5; Y-tract-tract of sequential pyrimidines
      with Yn>or=5). In species widely employing "intron definition" in the splicing
      process, the Y content of introns of the three targeted groups appeared to be
      higher compared to the control group. Furthermore, in all examined species, the
      introns of the targeted genes have a lower abundance of R-tracts compared to the
      control. We hypothesized that the R-Y composition of the targeted gene groups
      contributes to high rate and efficiency of both splicing and translation, in
      addition to the mRNA coding role. This is presumably achieved by (1) reducing the
      possibility of the formation of secondary structures in the mRNA, (2) using the R
      tracts and R-biased sequences as exonic splicing enhancers, (3) lowering the
      amount of targets for pyrimidine tract binding protein in the exons, and (4)
      reducing the amount of target sequences for binding of serine/arginine-rich (SR)
      proteins in the introns, thereby allowing SR proteins to bind to proper (exonic)
      targets.

PMID- 17211553
TI  - Vasovagal syncope in patients with reduced left ventricular function.
AB  - Vasovagal syncope (VVS) is mediated by arterial mechanoreceptors, resulting in
      reflexive changes in heart rate and vascular tone. The Bezold-Jarisch reflex was
      originally described as enhanced contraction and activation of left ventricular
      mechanoreceptors, but later studies implicated other triggers, including
      coronary, carotid, and cerebral arterial mechanoreceptors. VVS is uncommon in
      patients with left ventricular dysfunction. We hypothesized that VVS could occur
      in this subset and examined patient characteristics and hemodynamic responses
      during tilt table testing. From 1996 through 1998, 128 consecutive patients with
      ejection fraction <40% underwent tilt table testing (70 degrees , 45 min). A
      total of 15 patients (11.7%) had a positive neurocardiogenic response thought to
      be the cause of syncope. Clinical data and hemodynamic responses were reviewed.
      Mean patient age (+/-SEM) was 70.1 +/- 12.2 years. Nine patients were male. Mean
      ejection fraction was 27.7% +/- 7.1%. Thirteen had electrophysiologic studies
      with normal findings or abnormal findings insufficient to account for syncope.
      Hemodynamic analysis of 14 patients who had a vasovagal response during passive
      tilt table testing showed a mean time to positive response of 17.6 +/- 12.7 min.
      Cardioinhibitory responses (pauses >3 sec or heart rate < 40 beats/min for > or
      =10 sec) were not observed. Five responses were classified as mixed type (>10%
      decrease in heart rate without a cardioinhibitory response) and 9 as
      vasodepressor type (< or =10% decrease in heart rate). VVS occurs in patients who
      have clinically significant left ventricular dysfunction. Although this study had
      a small cohort size, the predominantly vasodepressor response without a
      cardioinhibitory component warrants further investigation into mechanisms of VVS
      in these patients.

PMID- 17211554
TI  - Microbleeds on gradient-echo T2(*)-weighted MR images from patients with multiple
      simultaneous intracerebral haemorrhages.
AB  - BACKGROUND: Multiple simultaneous intracerebral haemorrhages (ICH) occur rarely
      and the mechanism remains unknown. In this report, we compare several clinical
      factors of multiple haemorrhages, including microbleeds, with single
      intracerebral haemorrhages and discuss a potential explanation for their
      occurrence. METHODS: One hundred and ninety consecutive patients with
      intracerebral haemorrhage who were admitted within 24 hours after onset from
      January 2003 to November 2005 were included in the study. Several clinical
      factors, including the number of microbleeds on gradient-echo T2(*)-weighted
      magnetic resonance images, were compared between patients with single and
      multiple haemorrhages. FINDINGS: Computed tomography scans revealed that nine
      patients had multiple intracerebral haemorrhages. In all cases, five or more
      microbleeds were revealed on T2(*)-weighted magnetic resonance images. This was
      significantly higher than the number of microbleeds in patients with single
      intracerebral haemorrhage (p < 0.05). Systolic blood pressure on admission was >
      or =200 mmHg in seven of the nine patients and was higher than in patients with a
      single haemorrhage (p = 0.05). CONCLUSIONS: Elevated blood pressure induced by an
      initial haemorrhage was speculated to be the result of secondary haemorrhages in
      some patients with multiple microbleeds. Thus, strict blood pressure control may
      help to prevent the occurrence of multiple haemorrhages.

PMID- 17211556
TI  - Serum protease inhibitor concentrations and total antitrypsin activity in
      diabetic and non-diabetic children during adolescence.
AB  - The aim of the study was the assessment of the concentrations and establishment
      of mutual relationships between three main protease inhibitors: alpha-1
      antitrypsin (AAT), alpha-2-macroglobulin (alpha-2-M) and antithrombin-III (AT
      III), and of the total trypsin inhibitory capacity (TIC) in the serum of diabetic
      and non-diabetic children during adolescence. Forty-nine children (24 girls and
      25 boys) with type 1 diabetes mellitus and 24 non-diabetic children (13 girls and
      11 boys) were divided according to the Tanner scale into three groups: pre-, peri
      and post-pubertal. The concentrations of AAT, alpha-2-M and AT-III were
      determined by the radial immunodiffusion method on NOR-Partigen plates (Dade
      Behring), while TIC was determined by the method using BAPNA as substrate. Means
      and medians of serum AAT [1.55 g/l, 1.40 (95% confidence interval, 1.42-1.68),
      respectively] and TIC [10.6 mg trypsin/100 ml, 10.3 (95% CI, 9.5-11.7)] in
      diabetic children were lower than means and medians of AAT [1.81 g/l, 1.60 (95%
      CI 1.55-2.07), respectively] and TIC [12.5 mg trypsin/100 ml, 13.2 (95% CI, 10.9
      14.1)] in non-diabetic children. A comparison of variables between Tanner groups
      shows an increasing trend of AAT concentration in diabetic children and a
      decreasing trend of TIC in non-diabetic subjects. In contrast to pre- and peri
      puberty, no correlations were found in the postpubertal period between the
      studied parameters, either in diabetic or non-diabetic patients. Hyperglycaemia
      and the duration of diabetes were found to have a significant association with
      alpha-2-M and AT-III concentrations, but not with AAT serum concentrations. The
      concentrations and correlations between serum protease inhibitors in diabetic
      children during adolescence are disrupted compared with non-diabetic children.
      Taking into account the unfavourable consequences of vascular complications
      resulting from serum trypsin inhibitor changes and protease- antiprotease
      imbalance, diabetic children are at greater risk of this occurring during
      adolescence.

PMID- 17211557
TI  - Lack of association between the fatty acid binding protein 2 (FABP2) polymorphism
      with obesity and insulin resistance in two aboriginal populations from Chile.
AB  - The aim of this study was to assess the frequency of fatty acid binding protein 2
      (FABP2) Ala54Thr genetic polymorphism and to evaluate its association with
      obesity and insulin resistance in Chilean aboriginal populations. A sample of 96
      urban Aymara and 111 urban Mapuche subjects aged 20-80 years were recruited for
      this cross-sectional study. Glucose, insulin and lipid profile were measured in
      fasting plasma samples. Insulin resistance was estimated through the HOMA-IR
      model. FABP2 Ala54Thr genotypes were determined by PCR followed by RFLP analysis.
      The allele frequency of Thr54 variant was estimated as 18.2% in Aymara subjects,
      which is one of the lowest reported to date. The corresponding frequency in
      Mapuche subjects was 31.9% (p<0.002). Regarding genotype-phenotype associations,
      no significant differences were found in any of the anthropometric or metabolic
      variables according to Ala54Thr genotypes. After adjustment by BMI and metabolic
      variables through a logistic regression analysis, the association of the FABP2
      polymorphism with ethnic group persisted (Mapuche group: OR=2.37, 95% CI 1.319
      4.277, p=0.004) It is unlikely that Ala54Thr polymorphism of the FABP2 gene plays
      a relevant role in obesity and insulin resistance in Chilean ethnic groups.

PMID- 17211558
TI  - Genetic polymorphism within human growth hormone gene region and BMI in type 2
      diabetes.
AB  - Currently there is a surge of interest in the association of obesity with growth
      hormone (GH). Our hypothesis is that genetic variation within the hGH area could
      predispose to obesity in type 2 diabetes. We examined 68 Caucasian subjects with
      type 2 diabetes from the central area of Continental Italy. In these subjects we
      examined four polymorphic loci (Msp1A, Msp1B, BglIIA and BglIIB) located in the
      hGH gene region (chromosome 17q22-9-24). A sample of 192 adults from the
      population of Central Italy were studied as controls. Msp1B and Msp1A
      polymorphisms are associated with BMI. For both polymorphisms the proportion of
      overweight subjects is greater in the *1/*1 genotype than in carriers of the *2
      allele (97% vs. 79% and 94% vs. 86% respectively). For both polymorphisms, the
      mean value of BMI is greater in the *1/*1 genotype than in carriers of the *2
      allele. The mean values of age at onset of diabetes are greater in Msp1B*1/*1 and
      Msp1A*1/*1 genotypes than in carriers of the *2 allele. BglIIA and BglIIB
      polymorphisms are not associated with being overweight. The present study
      suggests that the structural organisation of the hGH genomic area may have an
      important role in being overweight associated with type 2 diabetes.

PMID- 17211559
TI  - Protective effect of high-dose thiamine (B1) on rat detrusor contractility in
      streptozotocin-induced diabetes mellitus.
AB  - We investigated the effect of thiamine (B1) treatment on bladder dysfunction in
      streptozotocin (STZ)-induced diabetic rats. A total of 40 rats were randomly
      divided into four groups: a control group, a group given thiamine only, a
      diabetic group and a diabetic group given thiamine therapy. Diabetes was induced
      in the rats by 65 mg/kg STZ via an intraperitoneal injection. Thiamine was given
      50 mg/kg/day. Diabetic cystopathy was confirmed on cystometry 8 weeks later in
      diabetic groups. Rats' body and bladder weights were measured. Contractile
      response to carbachol and potassium chloride (KCl) of detrusor strips in all
      groups was studied in vitro. The body weights were significantly decreased
      (p<0.01), the bladder weights were significantly increased (p<0.01), and the
      cystometric bladder capacity and the residual urine volumes were significantly
      increased (p<0.001, p<0.01 respectively) in STZ-induced diabetic groups compared
      to the control group and the group given thiamine only. Contractile responses
      increased in the diabetic group in high carbachol and KCl concentrations (p<0.01,
      p<0.01, respectively). On the other hand, there were no differences in the other
      groups. These data suggest that high-dose thiamine (B(1)) treatment may be
      beneficial in delaying the progression of diabetic cystopathy in this
      experimental animal model.

PMID- 17211560
TI  - Effects of type 2 diabetes mellitus on plasma fatty acid composition and
      cholesterol content of erythrocyte and leukocyte membranes.
AB  - Insulin resistance is a major factor in the pathogenesis of type 2 diabetes
      mellitus (T2DM) and is related to the fatty acid profile of the plasma membranes.
      The purpose of the present study was to investigate fatty acid composition and
      cholesterol content of cell membranes in patients with type 2 diabetes and, thus,
      to evaluate the possible factors leading to the alteration of plasma membrane
      fluidity. The study was performed in 20 healthy control subjects and 32 patients
      with type 2 diabetes. The fatty acid profiles and cholesterol content of the
      erythrocyte (RBC) and leukocyte (WBC) membranes were determined by a gas
      chromatographic method. When one considers the membrane constituents increasing
      fluidity and the ones decreasing it, the diabetics had a membrane composition
      decreasing fluidity compared to controls. On the other hand, when compared to
      control subjects, type 2 diabetic patients showed a significantly higher
      proportion of C16:0 components in erythrocyte and leukocyte membranes and plasma
      samples (25.4+/-3.1% vs. 31.1+/-4%; 23.3+/-2.4% vs. 29.3+/-5.2%; 27.6+/-3.9% vs.
      34.5+/-5.7%; p<0.005, p<0.01 and p<0.005, respectively). Our results suggest that
      the ratio of saturated:unsaturated fatty acids changes in plasma and cell
      membranes of patients with type 2 diabetes. This situation may cause, at least in
      part, RBC-WBC function abnormalities and insulin resistance because of
      inconvenient membrane fluidity.

PMID- 17211561
TI  - Clinical risk factors and the role of VDR gene polymorphisms in diabetic
      retinopathy in Polish type 2 diabetes patients.
AB  - Evidence exists that some clinical, metabolic and genetic risk factors are
      associated with the development of diabetic retinopathy (DR). The aim of the
      study was: (1) to define the prevalence of DR in the examined group of 267
      patients with type 2 diabetes mellitus (T2DM) from a Polish population; (2) to
      identify in cross-sectional analysis, the clinical features associated with DR in
      the study group; and (3) to search for the association of 4 markers of vitamin D
      receptor (VDR), a candidate gene for vascular complications in diabetes, with DR.
      The examined group consisted of 146 female and 121 male T2DM patients (mean age
      at examination: 61.3+/-9.4 years; age at T2DM diagnosis: 50.0+/-9.2; T2DM
      duration: 11.3+/-7.8 years; body mass index (BMI): 30.5+/-5.5 kg/m(2); HbA1c:
      7.8+/-1.5%). In all patients, the clinical and metabolic profile was determined.
      Diagnosis of DR was determined by a trained ophthalmologist by ophthalmoscopy
      after pupillary dilatation. Colour photographic documentation was made. The
      examined T2DM patients were genotyped for FokI, ApaI, BsmI and TaqI frequent VDR
      polymorphisms based on the restriction fragment length polymorphism method. The
      statistical analysis was performed using univariate and multivariate logistic
      regression (SAS) and haplotype analysis (Haplostat). DR was detected in 85
      (31.8%) patients with T2DM. The multivariate analysis revealed that significant
      predictors of this complication were: never-smoking status (odds ratio 2.2, 95%
      confidence interval 1.2-4), urea serum level (1.3, 1.1-1.5), HbA1c level (1.4,
      1.1-1.8) and insulin treatment (2.7, 1.4-5.1). Other features such as age of T2DM
      diagnosis, T2DM duration prior to ophthalmic exam, obesity (BMI>30), serum
      creatinine level, albumin/creatinine ratio and arterial hypertension were
      univariate predictors of DR, however they lost significance as independent
      predictors in multivariate analysis. Similarly, the alleles, genotypes, haplotype
      and haplotype combination of VDR were not associated with the examined
      complication. However, there was a suggestion of a possible slight association
      between the fbaT haplotype and DR (p=0.11). In conclusion, our study showed that
      DR in T2DM patients remains a frequent complication in Polish T2DM patients. We
      were able to confirm the role of some clinical risk factors, surprisingly
      including not-smoking status, as was previously shown in the UK Prospective
      Diabetes Study (UKPDS). VDR gene polymorphisms did not constitute a risk factor
      for this size of study group.

PMID- 17211562
TI  - Prevalence of metabolic syndrome in an elderly Swedish population.
AB  - The prevalence of the metabolic syndrome in different elderly European
      populations has not been well studied. The aim of this study was to measure the
      prevalence of metabolic syndrome, as well as its individual components, in an
      elderly Swedish cohort. A random sample of 778 individuals (372 men and 406
      women) was selected from a 70-year-old cohort in the H70 study, a gerontological
      and geriatric population study carried out in Gothenburg, Sweden. The study
      included medical and treatment history assessments, laboratory procedures and
      physical examinations to determine the presence of each of the five components of
      the metabolic syndrome as defined by the National Cholesterol Education Program
      Adult Treatment Panel III. Of the 508 adults (243 men and 265 women) included in
      the study, 22.6% had metabolic syndrome. The prevalence was higher in men (26.3%)
      than in women (19.2%). One third of the total sample had at least one of the five
      risk factors for metabolic syndrome. High blood pressure (> or =130/85 mmHg or
      use of antihypertensive/diuretic medication) was the most prevalent risk factor
      in both men (68.3%) and women (50.2%), while abdominal obesity was the overall
      second most common risk factor (27.2% of men and 42.7% of women). The prevalence
      of high fasting plasma glucose (> or =110 mg/dl or use of antidiabetic
      medication) was 29.0% in men and 19.1% in women. Metabolic syndrome was prevalent
      in a significant proportion of this elderly Swedish population, highlighting the
      underdiagnosis of a condition that is important to treat.

PMID- 17211563
TI  - Management of diabetic ketoacidosis in a teaching hospital.
AB  - The aim of our study was to evaluate clinical management of diabetic ketoacidosis
      (DKA) in a teaching hospital. We followed all the patients hospitalised for DKA
      over six years (1995-2000), and we recorded clinical data, laboratory finding at
      entrance and clinical management. We compared the data to the standards set in
      guidelines. Our study showed an important delay of initiation of intravenous
      fluid (70% of cases), an under-replacement with intravenous fluid (69% of cases)
      and with potassium therapy (80% of cases), and an excessive use of alkali
      therapy. In conclusion, suboptimal management of DKA occurred in a large
      percentage of patients.

PMID- 17211564
TI  - The effect of the sulfonylurea glyburide on glutathione-S-transferase and glucose
      6-phosphate dehydrogenase in streptozotocin-induced diabetic rat liver.
AB  - Free radical-induced lipid peroxidation has been associated with numerous disease
      processes including diabetes mellitus. Glutathione-S-transferase (GST) catalyses
      the conjugation of glutathione with a variety of organic peroxides to form more
      water-soluble compounds. Glucose-6-phosphate dehydrogenase (G6PDH) is essential
      to control intracellular reductive potential by increasing glutathione
      intracellular levels, which in turn decrease the amount of reactive oxygen
      species. Glyburide decreases glucose production and enhances insulin action in
      liver. The aim of this study was to examine the effects of glyburide on the
      antioxidant enzyme activities in the liver tissue of diabetic rat. We
      investigated the activities of GST and G6PDH in the liver of both control and
      streptozotocin-induced diabetic rats. Forty male albino rats were included in
      this study. Liver GST and G6PDH activities decreased significantly in five-week
      diabetic rats (p<0.001 and p<0.001 respectively) compared to controls and
      glyburide therapy restored these activities (p<0.001 for GST and p<0.001 for
      G6PDH). Elevations of hepatic antioxidant enzymes with glyburide administration
      suggest that glyburide may directly alter hepatic enzyme activities.

PMID- 17211565
TI  - Effect of quercetin on galactose-induced hyperglycaemic oxidative stress in
      hepatic and neuronal tissues of Wistar rats.
AB  - In recent times there has been great demand for natural products that have
      possible preventive action against diabetes and its secondary complications.
      Keeping this in mind, this study was undertaken to investigate the influence of
      the flavonoid, quercetin, on oxidative stress markers and the antioxidant defence
      system of hepatic and neuronal tissues from galactose-induced hyperglycaemic
      rats. Weanling male Wistar rats were treated with 30% galactose in AIN 93 diet
      (group B, n=8) to induce hyperglycaemia. Control rats received normal Stock AIN
      93 diet (group A, n=8). The third set of rats received group B diet with
      quercetin at 400 mg/100 g diet (group C, n=8). Glucose levels and body weights
      were measured on a weekly basis for four weeks to monitor the hyperglycaemia
      induced by galactose feeding. Parameters involved in the pathogenesis of
      galactose-induced hyperglycaemia, which included organosomatic index, protein
      content, antioxidant enzymes superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GSH-Px), tryptophan fluorescence, content of protein
      carbonyls, prooxidant malonaldehyde (MDA) and glutathione (GSH) in hepatic and
      neuronal tissues were determined at the end of the fourth week. The study suggest
      that quercetin counters the pro-oxidant effects of galactose-induced
      hyperglycaemic stress, as there was a significant reversal of changes with
      respect to body weights, organosomatic index of hepatic and neuronal tissues,
      lipid peroxidation, protein carbonyl content, reduced glutathione and activities
      of antioxidant enzymes. In addition, treatment with quercetin appears to reduce
      the osmotic stress induced by hyperglycaemia, as assessed by polyol pathway
      enzyme aldose reductase. These results imply that inclusion of quercetin in the
      diet controls, to some extent, galactose-induced hyperglycaemia and its attendant
      complications.

PMID- 17211566
TI  - Factors affecting adult knowledge of diabetes in Narlidere Health District,
      Turkey.
AB  - The objective was to determine the level of knowledge on diabetes in an adult
      population in Turkey. In this cross-sectional study, 524 people aged over 30 were
      selected from the population of Narlidere Health District, Izmir, Turkey. A
      questionnaire was performed to determine sociodemographic characteristics and
      knowledge of diabetes. Each item on the questionnaire was given a score with a
      possible final total of 100 points. Knowledge level was evaluated in the whole
      group, DM-positive and -negative groups. "DM-positive" group refers to
      respondents who either have diabetes themselves or whose relatives have it. "DM
      negative" group refers to respondents who do not have diabetes themselves and
      whose relatives do not. In total, 479 people were included in the study (response
      rate=87.6%). The mean age of the study group was 50.2+/-12.8 and 61% of them were
      women. Mean diabetes knowledge scores were 62.9+/-17.9 for the study group,
      68.3+/-16.1 for the "DM-positive" group and 60.6+/-18.2 for the "DM-negative"
      group. The "DM-negative" group had a significantly lower mean score than the
      other two groups. Overall, diabetes knowledge was higher in participants with
      diabetes or who had a relative with diabetes, who were educated for more than 5
      years and who had health insurance. The diabetes knowledge of the study group was
      not satisfactory. Diabetics and people who have relatives with diabetes had a
      higher knowledge level than the population without diabetes. Detailed information
      regarding diabetes should be provided to not only diabetics, but also the
      population as a whole.

PMID- 17211568
TI  - The diabetic foot: a plea for the elementary?
AB  - The outlook for the diabetic foot today is still not as favourable as it could
      be. This holds true, despite the progress that has been achieved in the care of
      both the neuropathic and the neuroischaemic foot. Regrettably, misconceptions
      abound among the non-specialists. Yet the situation will not be improved, unless
      every health care provider involved in the management of diabetic patients
      commands an absolute minimum of knowledge regarding the prevention and management
      of foot lesions. Indeed, more forceful implementation of elementary knowledge is
      needed, coupled with continuous education and research, to reduce the number of
      amputations.

PMID- 17211567
TI  - Preprandial repaglinide decreases exogenous insulin requirements and HbA1c levels
      in type 2 diabetic patients taking intensive insulin treatment.
AB  - In this study, we investigated the effects of combining preprandial repaglinide
      to the insulin therapy for reducing the exogenous insulin requirements and serum
      HbA(1c) levels in type 2 diabetic patients whose blood glucose levels were
      previously regulated by multiple dose intensive insulin therapy. Fifty patients
      with type 2 diabetes who had been initially treated with oral antidiabetic agents
      without a satisfactory response were included in this study. After adequate
      glycemic control was achieved with intensive insulin therapy, the patients were
      divided into two subgroups. The first group continued with intensive insulin
      therapy. The second group received a combination of multiple insulin injections
      and oral repaglinide (1.5 mgr tid). The doses of insulin injections were
      gradually decreased accordingly in the second group. Both groups were followed-up
      for 3 months. Repaglinide was well tolerated and had no toxicity. A significant
      reduction regarding exogenous insulin requirements and serum HbA(1c) levels were
      demonstrated in patients taking preprandial repaglinide (p<0.01). Combining
      repaglinide to intensive insulin therapy could be a safe and effective
      alternative to intensive insulin therapy alone for the glycemic control and for
      reducing exogenous insulin requirements in type 2 diabetic patients.

PMID- 17211569
TI  - Antiviral effects of pan-caspase inhibitors on the replication of coxsackievirus
      B3.
AB  - The induction of apoptosis during coxsackievirus B3 (CVB3) infection is well
      documented. In order to study whether the inhibition of apoptosis has an impact
      on CVB3 replication, the pan-caspase inhibitor Z-VAD-FMK was used. The decreased
      CVB3 replication is based on reduced accumulation of both viral RNA and viral
      proteins. These effects are due to an inhibitory influence of Z-VAD-FMK on the
      proteolytic activity of the CVB3 proteases 2A and 3C, which was demonstrated by
      using the target protein poly(A)-binding protein (PABP). The antiviral effect of
      the structurally different pan-caspase inhibitor Q-VD-OPH was independently of
      the viral protease inhibition and resulted in suppression of virus progeny
      production and impaired release of newly produced CVB3 from infected cells. A
      delayed release of cytochrome c into the cytoplasm was detected in Q-VD-OPH
      treated CVB3-infected cells pointing to an involvement of caspases in the initial
      steps of mitochondrial membrane-permeabilization.

PMID- 17211570
TI  - Editorial - how bad is medical education research anyway?

PMID- 17211571
TI  - Kidney transplants in patients with bladder augmentation: correlation and
      evolution.
AB  - OBJECTIVE: To review the literature, analyse the evolution of kidney transplants
      (KT) in patients with bladder augmentation (BA) and investigate the relation
      between BA and KT. MATERIALS AND METHODS: Six patients with a history of severe
      lower urinary tract dysfunction and BA, received a KT at our Unit between 1993
      and 2003. Three had moderate renal failure at the moment of the BA. The remaining
      three had end stage renal failure. RESULTS: With a follow-up of 7 years (mean) we
      have a patient survival of 100% and a graft survival of 83%. No complications
      occurred between the BA and the KT. The few KT complications were not related to
      BA. CONCLUSION: When a bladder dysfunction is present, it should be treated
      before KT. In noncompliant bladders, BA is the best treatment. This can be done
      to try to avoid end stage renal failure or only to prepare the lower urinary
      tract for reception of the transplant. The presence of a BA did not worsen the
      evolution of the KT.

PMID- 17211572
TI  - A comparison of clinical features between chlamydial and non-chlamydial
      urethritis in men negative for gonococcal infection who attended a urological
      outpatient clinic in Japan.
AB  - OBJECTIVES: The objective of this study was to investigate the clinical features
      of non-gonococcal urethritis in men who attended a urological outpatient clinic
      in Japan. MATERIALS AND METHODS: This study included a total of 194 patients
      diagnosed as having non-gonococcal urethritis and subsequently judged as cured
      following antibiotic therapy between January 2001 and June 2005. Clinical data
      were analyzed after dividing these patients into two groups as follows: 96
      patients with chlamydial urethritis (CU) and 98 with non-chlamydial urethritis
      (NCU). RESULTS: The incubation period in the CU group was significantly longer
      than that in the NCU group (P = 0.0020). The incidence of severity of symptoms in
      the NCU group was significantly greater than that in the CU group (P = 0.022),
      and the interval between the appearance of the initial symptom and consulting the
      clinic was significantly shorter in the NCU group than in the CU group (P =
      0.0015). The proportion of commercial sex workers (CSWs) as the causative partner
      in the NCU group was significantly greater that in the CU group (P < 0.001), and
      the incidence of oral sex as the causative mode of sexual interaction was
      significantly more frequent in the NCU group than that in the CU group (P =
      0.021). The duration of antibiotic therapy until cured was significantly longer
      in the CU group than in the NCU group (P = 0.0051). Furthermore, multivariate
      analysis showed that whether the infection involved CU or NCU was independently
      associated with the treatment interval irrespective of other factors examined (P
      = 0.041). CONCLUSIONS: These findings suggest that the clinical characteristics
      of CU and NCU clearly differ and that CU tends to require a longer time to cure
      than NCU; therefore, among patients with non-gonococcal urethritis, it would be
      particularly important to effectively control the spread of CU.

PMID- 17211574
TI  - Glomerular mesangial fibrillary deposits in a patient with diabetes mellitus.
AB  - Various systemic or primary glomerular diseases can result in deposition of
      fibrillary material in the glomerular tuft and may cause an important diagnostic
      challenge for the pathologists. Biopsy findings of a patient with type 2 diabetes
      is presented here in which striking fibrillary structures were identified in the
      mesangium by ultrastructural examination. The distinction between diabetic
      fibrillosis and fibrillary glomerulonephritis accompanying diabetic nephropathy
      is discussed in the setting of a literature review.

PMID- 17211573
TI  - Multiple/bilateral renal tumors in patients with Birt-Hogg-Dube syndrome.
AB  - OBJECTIVE: To describe our findings in four patients with multiple/bilateral
      renal cell carcinoma (RCC) and Birt-Hogg-Dube (BHD) syndrome. PATIENTS AND
      METHODS: A series of four patients with BHD syndrome and RCC is analyzed. Patient
      charts were reviewed for age, sex, presentation, various clinical manifestations,
      imaging, management and outcome. RESULTS: Patients included 2 males and 2
      females. Age ranged from 40 to 65 years (mean 56 years). The interval between the
      diagnosis of skin lesions characteristic of the disease and the development of
      renal tumors ranged between 1 and 35 years. Three of the patients had bilateral
      renal tumors (2 synchronous and one metachronous), one patient had multiple renal
      tumors in one kidney. In one patient the renal mass was diagnosed with a
      screening CT scan of the abdomen after the diagnosis of BHD syndrome. One patient
      had associated spontaneous pneumothorax and thyroid tumor. Only one of the 4
      patients had prior family history of BHD syndrome. Renal tumors were clear cell
      type in 3 patients, and chromophobe tumor in one. Tumor size ranged from 2 to 9
      cm. CONCLUSION: BHD syndrome is associated with multiple diseases and tumors. We
      describe four patients with BHD syndrome with multiple or bilateral RCC. Two of
      the patients were asymptomatic. A high index of suspicion should be present in
      patients who present with the characteristic skin lesions of BHD syndrome and
      screening for the presence of renal tumors should be done in those patients. Long
      term follow up is necessary after treating renal tumors in these patients.

PMID- 17211575
TI  - Management of atherosclerotic renovascular disease: the effect of renal artery
      stenting on renal function and blood pressure.
AB  - In the last few years, renal artery stenting has gradually evolved into one of
      the most important therapeutic modalities in the management of atherosclerotic
      renovascular disease. Stenting is nowadays preferred by a steadily increasing
      number of physicians, not only because of its significant contribution to blood
      pressure control, but also because of its documented ability to maintain, and
      even improve, renal function. At the same time, procedure-related morbidity and
      mortality rates are extremely low, while recurrent stenosis rates have been
      repeatedly reported to be minimal. Percutaneous transluminal renal angioplasty
      (PTRA) and stenting are nowadays considered by many physicians to be the
      treatment of choice for atherosclerotic renovascular disease.

PMID- 17211576
TI  - Basal and infection-induced levels of heat shock proteins in human aging.
AB  - Heat shock proteins (Hsp) are ubiquitously expressed proteins, which are highly
      inducible by a variety of stressful stimuli. As organisms age, various denatured
      proteins such as proteins modified by oxidation have been detected. Such abnormal
      proteins might serve as stress signals for the induction of Hsp, which plays
      indispensable roles in protecting proteins from denaturation. Although it is well
      known that the heat shock induced expression of Hsp decreases with age, little
      attention has been given to the unstimulated, basal levels of Hsp. Therefore, a
      study was performed to examine the expression pattern of various Hsp with aging,
      under normal physiological conditions in human peripheral blood cells. The basal
      levels of Hsp32, Hsp70 and Hsp90 increased significantly with age in controls but
      not patients. Moreover, the levels of Hsp32, Hsp70, Hsp90, but not Hsp27
      correlated positively among each other, indicating both common and different
      regulatory mechanisms. Higher levels of Hsp32, Hsp70 and Hsp90 were noticed in
      patients with inflammation, a commonly occurring natural stimulant of Hsp
      production, compared to control subjects. The production of Hsp appeared to be
      related to the circulating levels of C-reactive protein and cytokines.

PMID- 17211577
TI  - An approach to the validation of novel molecular markers of breast cancer via TMA
      based FISH scanning.
AB  - Tissue microarrays (TMA) are valuable tools for validating results of array-based
      comparative genomic hybridization (ACGH) and other translational research
      applications requiring independent verification of genomic gains and losses by
      fluorescence in situ hybridization (FISH). However, spatial orientation and
      accurate manual tracking of the TMA cores is challenging and prone to error.
      Image analysis combined with core tracking software, implemented via an automated
      FISH scanning workstation, represents a new approach to FISH and TMA-based
      validation of novel genomic changes discovered by ACGH in breast and other
      cancers. Automated large-scale tissue microarray validation FISH studies of
      genomic gains and losses identified by ACGH for breast cancer are feasible using
      an automated imaging scanner and tracking/classifying software. Furthermore, by
      leveraging the bifunctional fluorescent and chromogenic properties of the
      alkaline phosphatase chromogen fast red K and combining the technology with FISH,
      correlative and simultaneous phenotype/genotype studies may be enabled.

PMID- 17211578
TI  - The quality of self-care counselling by pharmacy practitioners, supported by IT
      based clinical guidelines.
AB  - OBJECTIVE: The primary objective of the study was to assess the quality of self
      care counselling from pharmacy practitioners, supported by national clinical
      guidelines. The research questions addressed (1) the distribution of symptoms
      among customers in need of self-care counselling, (2) the quality of the self
      care advice provided by pharmacy practitioners, (3) the degree of customer
      compliance with appropriate pharmacy advice versus the extent of symptom relief,
      (4) and versus a subsequent medical care visit, and (5) which resource the
      customers would have turned to in the first place for their ailments, had the
      pharmacy practitioner not been available. SETTING: Three large community
      pharmacies with non-prescription self-selection departments in central Sweden.
      METHODS: Ten pharmacy practitioners counselled all customers > or = 18 years old,
      with whom a dialogue was initiated on advice or products for self-care. The
      counselling was based on national clinical guidelines for self-care advice in the
      form of a software decision support program. The data collection consisted of
      documentation of background customer information, independent assessments of the
      quality of the advice provided and of telephone follow-ups. RESULTS: Of all
      documented symptoms (n = 250), the most common were allergy (26.4%),
      musculoskeletal symptoms (8.4%) and dyspepsia (7.2%). Independent assessments of
      the documentation by a physician and a pharmacist found that self-care advice was
      appropriate to give 97.6% of the customers and that the advice provided was
      correct in 88.4% of the cases. In total, 217 cases (86.8%) were fully approved by
      both the physician and the pharmacist. Among the 182 customers who claimed that
      they complied completely with appropriate advice provided, 135 (74.2%)
      experienced a great improvement in symptoms. Among the 21 who had only partly
      followed the advice, six (28.6%) reported the same level of improvement (p <
      0.001). If the pharmacy practitioner had not been available, 56.8% of the
      customers would have turned to medical care in the first instance. CONCLUSIONS:
      The study demonstrates the high quality of pharmacy practitioners' self-care
      counselling supported by IT-based national clinical guidelines, including a
      favourable impact on customers' ailments. Furthermore, it reveals that pharmacy
      practitioners greatly relieve the pressure on the health-care system, resulting
      in reduced costs to society.

PMID- 17211579
TI  - Quantification of cyclic electron flow around Photosystem I in spinach leaves
      during photosynthetic induction.
AB  - The variation of the rate of cyclic electron transport around Photosystem I (PS
      I) during photosynthetic induction was investigated by illuminating dark-adapted
      spinach leaf discs with red + far-red actinic light for a varied duration,
      followed by abruptly turning off the light. The post-illumination re-reduction
      kinetics of P700+, the oxidized form of the photoactive chlorophyll of the
      reaction centre of PS I (normalized to the total P700 content), was well
      described by the sum of three negative exponential terms. The analysis gave a
      light-induced total electron flux from which the linear electron flux through PS
      II and PS I could be subtracted, yielding a cyclic electron flux. Our results
      show that the cyclic electron flux was small in the very early phase of
      photosynthetic induction, rose to a maximum at about 30 s of illumination, and
      declined subsequently to <10% of the total electron flux in the steady state.
      Further, this cyclic electron flow, largely responsible for the fast and
      intermediate exponential decays, was sensitive to 3-(3,4-dichlorophenyl)-1,1
      dimethyl urea, suggesting an important role of redox poising of the cyclic
      components for optimal function. Significantly, our results demonstrate that
      analysis of the post-illumination re-reduction kinetics of P700+ allows the
      quantification of the cyclic electron flux in intact leaves by a relatively
      straightforward method.

PMID- 17211580
TI  - Photosynthetic acclimation in the context of structural constraints to carbon
      export from leaves.
AB  - The potential role of foliar carbon export features in the acclimation of
      photosynthetic capacity to differences and changes in light environment was
      evaluated. These features included apoplastic vs. symplastic phloem loading,
      density of loading veins, plasmodesmatal frequency in intermediary cells, and the
      ratio of loading cells to sieve elements. In initial studies, three apoplastic
      loaders (spinach, pea, Arabidopsis thaliana) exhibited a completely flexible
      photosynthetic response to changing light conditions, while two symplastic
      loaders (pumpkin, Verbascum phoeniceum), although able to adjust to different
      long-term growth conditions, were more limited in their response when transferred
      from low (LL) to high (HL) light. This suggested that constraints imposed by the
      completely physical pathway of sugar export might act as a bottleneck in the
      export of carbon from LL-acclimated leaves of symplastic loaders. While both
      symplastic loaders exhibited variable loading vein densities (low in LL and high
      in HL), none of the three apoplastic loaders initially characterized exhibited
      such differences. However, an additional apoplastic species (tomato) exhibited
      similar differences in vein density during continuous growth in different light
      environments. Furthermore, in contrast to the other apoplastic loaders,
      photosynthetic acclimation in tomato was not complete following a transfer from
      LL to HL. This suggests that loading vein density and loading cells per sieve
      element, and thus apparent loading surface capacity, play a major role in the
      potential for photosynthetic acclimation to changes in light environment.
      Photosynthetic acclimation and vein density acclimation were also characterized
      in the slow-growing, sclerophytic evergreen Monstera deliciosa. This evergreen
      possessed a lower vein density during growth in LL compared to HL and exhibited a
      more severely limited potential for photosynthetic acclimation to increases in
      light environment than the rapidly-growing, mesophytic annuals.

PMID- 17211582
TI  - Case study of combinatorial imaging: what protocol and what chlorophyll
      fluorescence image to use when visualizing infection of Arabidopsis thaliana by
      Pseudomonas syringae?
AB  - Localized infection of a plant can be mapped by a sequence of images capturing
      chlorophyll fluorescence transients in actinic light. Choice of the actinic light
      protocol co-determines fluorescence contrast between infected leaf segment and
      surrounding healthy tissue. Frequently, biology cannot predict with which
      irradiance protocol, in which fluorescence image of the sequence, and in which
      segment of the image there will be the highest contrast between the healthy and
      infected tissue. Here, we introduce a new technique that can be applied to
      identify the combination of chlorophyll fluorescence images yielding the highest
      contrast. The sets of the most contrasting images vary throughout the progress of
      the infection. Such specific image sets, stress-revealing fluorescence
      signatures, can be found for the initial and late phases of the infection. Using
      these signatures, images can be divided into segments that show tissue in
      different infection phases. We demonstrate the capacity of the algorithm in an
      investigation of infection of the model plant Arabidopsis thaliana by the
      bacterium Pseudomonas syringae. We show that the highest contrast is found with
      transients elicited by fluctuating, harmonically modulated irradiance with long
      periods.

PMID- 17211581
TI  - Complete nucleotide sequence of the freshwater unicellular cyanobacterium
      Synechococcus elongatus PCC 6301 chromosome: gene content and organization.
AB  - The entire genome of the unicellular cyanobacterium Synechococcus elongatus PCC
      6301 (formerly Anacystis nidulans Berkeley strain 6301) was sequenced. The genome
      consisted of a circular chromosome 2,696,255 bp long. A total of 2,525 potential
      protein-coding genes, two sets of rRNA genes, 45 tRNA genes representing 42 tRNA
      species, and several genes for small stable RNAs were assigned to the chromosome
      by similarity searches and computer predictions. The translated products of 56%
      of the potential protein-coding genes showed sequence similarities to
      experimentally identified and predicted proteins of known function, and the
      products of 35% of the genes showed sequence similarities to the translated
      products of hypothetical genes. The remaining 9% of genes lacked significant
      similarities to genes for predicted proteins in the public DNA databases. Some
      139 genes coding for photosynthesis-related components were identified. Thirty
      seven genes for two-component signal transduction systems were also identified.
      This is the smallest number of such genes identified in cyanobacteria, except for
      marine cyanobacteria, suggesting that only simple signal transduction systems are
      found in this strain. The gene arrangement and nucleotide sequence of
      Synechococcus elongatus PCC 6301 were nearly identical to those of a closely
      related strain Synechococcus elongatus PCC 7942, except for the presence of a
      188.6 kb inversion. The sequences as well as the gene information shown in this
      paper are available in the Web database, CYORF (http://www.cyano.genome.jp/).

PMID- 17211583
TI  - A method for quantitative analysis of spatially variable physiological processes
      across leaf surfaces.
AB  - Many physiological processes are spatially variable across leaf surfaces. While
      maps of photosynthesis, stomatal conductance, gene expression, water transport,
      and the production of reactive oxygen species (ROS) for individual leaves are
      readily obtained, analytical methods for quantifying spatial heterogeneity and
      combining information gathered from the same leaf but with different instruments
      are not widely used. We present a novel application of tools from the field of
      geographical imaging to the multivariate analysis of physiological images.
      Procedures for registration and resampling, cluster analysis, and classification
      provide a general framework for the analysis of spatially resolved physiological
      data. Two experiments were conducted to illustrate the utility of this approach.
      Quantitative analysis of images of chlorophyll fluorescence and the production of
      ROS following simultaneous exposure of soybean leaves to atmospheric O3 and
      soybean mosaic virus revealed that areas of the leaf where the operating quantum
      efficiency of PSII was depressed also experienced an accumulation of ROS. This
      correlation suggests a causal relationship between oxidative stress and
      inhibition of photosynthesis. Overlaying maps of leaf surface temperature and
      chlorophyll fluorescence following a photoinhibition treatment indicated that
      areas with low operating quantum efficiency of PSII also experienced reduced
      stomatal conductance (high temperature). While each of these experiments explored
      the covariance of two processes by overlaying independent images gathered with
      different instruments, the same procedures can be used to analyze the covariance
      of information from multiple images. The application of tools from geographic
      image analysis to physiological processes occurring over small spatial scales
      will help reveal the mechanisms generating spatial variation across leaves.

PMID- 17211585
TI  - The positive role of lumbar puncture in the diagnosis of Vogt-Koyanagi-Harada
      disease: lymphocyte subsets in the aqueous humor and cerebrospinal fluid.
AB  - PURPOSE AND METHODS: Activated T cells are believed to be important at the
      inflammatory sites in the pathogenesis of Vogt-Koyanagi-Harada disease. Patients
      are often affected by meningitis and uveitis. In this work, to examine the
      positive role of lumbar puncture in the diagnosis of VKH disease, we analyzed and
      compared the surface markers of aqueous humor cells, cerebrospinal fluid cells,
      and peripheral blood lymphocytes by use of flow cytometry. RESULTS: Most
      lymphocytes were T cells. In aqueous humor and cerebrospinal fluid, numbers of
      CD3(+), CD4(+), and CD4(+)CD45RO(+) cells were significantly greater than in
      peripheral blood lymphocytes (P < 0.01). The CD4(+)/CD8(+) ratio for aqueous
      humor and cerebrospinal fluid was significantly higher than that for peripheral
      blood cells (P < 0.01). Four weeks after starting systemic corticosteroid
      treatment, numbers of CD4(+) and CD4(+)CD45RO(+) cells in cerebrospinal fluid
      were significantly lower than before treatment. CONCLUSIONS: Profiles of surface
      markers were similar for cerebrospinal fluid and aqueous humor, but apparently
      different from that for peripheral blood cells. This suggests that cerebrospinal
      fluid may reflect the active local immunological reaction at sites affected by
      the disease, i.e. the uvea and the meninges.

PMID- 17211584
TI  - A two-photon excitation study on the role of carotenoid dark states in the
      regulation of plant photosynthesis.
AB  - Plants are exposed to sun light intensities that vary rapidly over several orders
      of magnitude during a typical day. It is known that the regulation of
      photosynthetic activity under these circumstances is essential for the survival
      and fitness of natural and gene modified plants. A quick balancing between
      utilization and dissipation of absorbed light energy ensures optimized levels of
      CO(2) fixation and protection from photo damage by excessive light-irradiation.
      Despite intensive investigations the biophysical mechanisms of these regulation
      processes are still poorly understood. Potentially involved singlet states of
      carotenoids are optically "dark" and so far it was impossible to investigate
      their role directly in living plants by conventional absorption or fluorescence
      spectroscopy. Here, we show by selective two-photon excitation of the carotenoid
      dark states in plant that a dominant part of the regulation is correlated with a
      substantial change in the energy transfer between these states and the
      chlorophylls (Chl). The results support a considerable role of the molecular gear
      shift model in which a reversible and step-wise enzymatic modification of the
      electronic structure of xanthophyll carotenoids enables a switching between
      carotenoid-to-Chl light-harvesting and Chl-to-carotenoid quenching. The shifting
      can be observed in real time in any plant. Treatment with the xanthophyll cycle
      inhibitor dithiothreitol slowed down both the light adaptation and the carotenoid
      Chl energy flow changes to the same extent. Based on these results, we propose a
      biophysical quenching model in which both carotenoid dark states and radical
      cations contribute to the dissipation of excessive excitation energy.

PMID- 17211586
TI  - Midgut malrotation and associated Hirschsprung's disease: a diagnostic dilemma.
AB  - Malrotation and Hirschsprung's disease (HSD) are rarely reported together. We
      report our experience with three patients who presented during the neonatal
      period in whom the association resulted in diagnostic difficulty. In this report,
      we focus on the clinical presentation, diagnosis and appropriate management.

PMID- 17211587
TI  - Expression of homeotic genes Hoxa3, Hoxb3, Hoxd3 and Hoxc4 is decreased in the
      lungs but not in the hearts of adriamycin-exposed mice.
AB  - Exposure of rat and mouse embryos to adriamycin (doxorubicin chlorhydrate)
      induces esophageal atresia (EA) and VACTERL association. Sonic hedgehog (Shh) and
      Gli2/Gli3 pathways are involved in these conditions and knockout mice for
      homeotic Hox genes Hoxa3, Hoxb3, Hoxc3, Hoxc4 and Hoxa5 show phenotypes with some
      of the associated VACTERL features. This study aims at evaluating the possible
      influence of Hoxa3, Hoxb3, Hoxd3 and Hoxc4 as upstream regulators of this complex
      signalling. Pregnant mice were exposed either to 4 mg/kg of adriamycin (EA group)
      or vehicle (controls) on embryonic days 7.5 and 8.5. Embryos were recovered at
      four endpoints (E12.5-E15.5) and randomly assigned for immunohistochemical or
      molecular biology studies. Lungs and hearts were separately harvested and
      processed for Hoxa3, Hoxb3, Hoxd3 and Hoxc4 quantitative RT-PCR measurements.
      Antibodies for Hoxa3, Hoxb3 and Hoxd3 proteins were used for immunohistochemical
      studies. RT-PCR studies showed a drastic and statistically significant decrease
      of the four genes in the lungs of EA mice when compared to controls, with a
      slight recovery from E15.5. Hearts of both groups showed a similar expression of
      all the genes throughout gestation. Control embryos expressed the hox3 paralogous
      genes in heart, skin, foregut derivatives and their surrounding mesoderm through
      E12.5-E15.5 whereas adriamycin-exposed embryos showed a severe decrease in
      expression of these three proteins in the same tissues but not in the heart.
      Adriamycin drastically reduced the expression of Hoxa3, Hoxb3, Hoxd3 and Hoxc4 in
      mice embryonic lungs. Their expression in the heart did not seem to be influenced
      by adriamycin in this experimental setting.

PMID- 17211588
TI  - Lack of association of IL8 gene polymorphisms with familial vesico-ureteral
      reflux.
AB  - Vesico-ureteral reflux (VUR) is the most common inherited disorder of the lower
      urinary tract. Children with VUR are at risk for ongoing renal damage with
      subsequent infections. IL8 is an important inflammatory mediator which can be
      produced by epithelial cells of the renal tract in response to a variety of
      inflammatory stimuli. High serum concentrations of IL-8 have been reported in
      patients with chronic renal failure. Elevated IL-8 levels have been reported in
      the urine of patients with VUR and renal parenchymal scarring (RPS). More
      recently it was reported that urine IL-8 levels remain elevated in infants with
      VUR even in the absence of a urinary tract infection (UTI). Increased IL-8
      expression has been shown to be associated with polymorphism at position -251
      (rs4073) of the IL-8 promoter. The aim of this study was to examine the
      association of IL-8 gene polymorphism with familial VUR in a cohort of 219
      siblings from 109 families affected with VUR, the largest such cohort tested to
      date. RPS was assessed using dimercaptosuccinic acid scintigraphy. Genotyping was
      performed in 219 siblings with VUR (157 without RPS, 62 with RPS) and 292
      controls for the position -251 of IL-8 gene by polymerase chain reaction with
      tetra primers and gel analysis. Genotype was compared using the chi square test.
      Statistical significance was taken as a value of P < 0.05. There were no
      significant differences in IL-8 -251 genotype frequency between VUR patients and
      controls. Similarly, gender, severity of VUR and renal parenchymal scarring had
      no effect on IL-8 -251 genotype frequency. Although IL-8 urinary levels have been
      reported to be elevated in VUR, our data indicate that IL-8 gene is not involved
      in the pathogenesis of familial VUR or reflux nephropathy.

PMID- 17211590
TI  - Effect of testicular ischemia-reperfusion on recruitment of neutrophils, E
      selectin expression and germ cell apoptosis in the contralateral testis in a rat.
AB  - Recent evidence suggests that neutrophil recruitment may initiate germ cell
      apoptosis in the ischemic testis. The purpose of the present study was to examine
      the relationship between germ cell apoptosis and neutrophil recruitment in the
      contralateral testis following testicular ischemia-reperfusion (IR) injury in a
      rat. Adult male Sprague-Dawley rats were divided randomly into two experimental
      groups: Group A: Sham operated animals; Group B: IR rats underwent 90 min of
      unilateral testicular ischemia following by 96 h of reperfusion. The rats were
      sacrificed and testes were harvested. Johnsen's criteria and the number of
      germinal cell layers were measured to categorize the spermatogenesis. TUNEL assay
      was used to determine germ cell apoptosis in both the ischemic and contralateral
      testis. The recruitment of neutrophils was calculated per 100 venules. Expression
      of E-selectin was determined using immunohistochemical analysis. Statistical
      analysis was performed using Student's t test, with P less than 0.05 considered
      statistically significant. Germ cell apoptosis in both the ischemic and the
      contralateral testis increased significantly after IR. E-selectin expression was
      significantly greater in ischemic testis from IR rats compared to sham animals.
      The small increase in E-selectin expression and the concomitant increase in
      neutrophil recruitment in the contralateral testis of the IR rats (vs. sham
      animals) were not statistically significant. In conclusion, testicular ischemia
      causes an increase in germ cell apoptosis in the contralateral testis. Mechanisms
      other than neutrophil recruitment apparently initiate this process.

PMID- 17211589
TI  - In vitro effects of adriamycin: a dose-response study.
AB  - The in vivo effects of adriamycin (ADR) on the mouse and rat embryos are well
      described in the literature. However, there is a lack of knowledge about the in
      vitro effects of ADR. The aim of this study was to investigate the effects of ADR
      on the developing mouse embryo and to identify a dose of ADR, which could be used
      for further studies of ADR effects in vitro. CD1 mouse embryos were collected at
      day 8.5 post conception. They were cultured in the presence of different doses of
      ADR (0, 125, 250, 375 and 500 microM). After 24 h, the culture was stopped and
      the embryos (n = 77) were scored morphologically using the Brown-Fabro scoring
      system and the mean score for each organ was calculated. Dose-response plots were
      generated and the effective dose 50 (ED50) for each organ was identified from the
      plots. The effects of ADR on the developing embryo were found to be dose related
      and there is a dose-response relationship in most of the plots. The dose-response
      plots were found to be parallel for some organs. A dose of 250 microM ADR was
      identified as the appropriate dose for further in vitro studies. The effects of
      ADR on the embryos were dose related and there is a dose-response relationship in
      most of the developing systems. The presence of parallel dose-response plots for
      some regions is suggestive of similar mechanism of action of ADR on these
      regions. A dose of 250 microM of ADR was identified for the first time in the
      literature and could be used for further studies of the effects of ADR on the
      mouse foregut in vitro.

PMID- 17211592
TI  - A frightening complication of general anaesthesia for paediatric dental
      extractions.
AB  - We report a case of eight year old child who developed severe subcutaneous
      emphysema, bilateral pneumothorax, pneumomediastinum and pneumoperitonium in
      recovery room after apparently uneventful general anaesthesia for eight primary
      teeth extractions. Causes and treatment of these complications are discussed.

PMID- 17211591
TI  - Effects of standard chemotherapy on tumor growth and regulation of multidrug
      resistance genes and proteins in childhood rhabdomyosarcoma.
AB  - The prognosis of rhabdomyosarcoma (RMS) in advanced stages is still sobering.
      Therapy is limited due to local tumor recurrence, development of metastases and
      multidrug resistance. The aim of this study was to investigate the development of
      multidrug resistance in cell lines and in xenografts of alveolar and embryonal
      RMS treated according to the German Soft Tissue Sarcoma Study (CWS). Alveolar and
      embryonal RMS cell lines were treated with Vincristine, Topotecan, Carboplatin,
      Actinomycin D, or Ifosfamide. Expression levels of resistance-associated genes
      were assessed using Real time-PCR. Nude mice (NMRI nu/nu, n = 10 per group)
      underwent xenotransplantation of human embryonal or alveolar RMS. Animals were
      treated with standard chemotherapeutic drugs Vincristine, Topotecan, Carboplatin,
      Actinomycin D, or Ifosfamide according to treatment schedules of the CWS-study.
      Tumor sizes were measured and relative tumor volumes were calculated. Animals
      were sacrificed after 20 days and standard histology, Real-time-PCR for MDR1-,
      MRP-, LRP- and MDM2-gene as well as immunohistochemistry for MDR1-, LRP-, and MRP
      protein were performed. In the cell lines, an up-regulation of MDR-1 gene was
      found in alveolar rhabdomyosarcoma. In embryonal rhabdomyosarcoma, an up
      regulation of LRP and MRP was found. Standard chemotherapy of alveolar
      rhabdomyosarcoma resulted in a significant reduction of tumor growth (P < 0.05)
      in all groups. In embryonal rhabdomyosarcoma strongest effects were found after
      treatment with Ifosfamide, Vincristine and Carboplatin (P < 0.05). RT-PCR
      revealed a MDR1-dependent mechanism in alveolar rhabdomyosarcoma. In embryonal
      rhabdomyosarcoma, MDR1 occurred to a lower degree. Immunohistochemistry revealed
      correlating expression levels of multidrug resistance-associated proteins. The
      use of established chemotherapy on human RMS in vivo had strong effects on
      xenografts compared to their controls. In all cases, there was only a reduction
      of tumor growth, but not a complete eradication of the tumors. Chemotherapy
      seemed to upregulate the expression of resistance-associated genes in vitro and
      in vivo. The mechanism of multidrug resistance depends on the tumor subtype.
      Therefore, further investigations will be required to evaluate multidrug
      resistance in patients and to investigate new modalities for a reversal of
      multidrug resistance.

PMID- 17211594
TI  - Chemiluminescent imaging analysis of interferon alpha in serum samples.
AB  - Enzyme-linked immunosorbent assay (ELISA), horseradish peroxidase (HRP)-catalyzed
      fluorescent reaction, and oxalate chemiluminescence imaging analysis have been
      combined to develop a sensitive, simple, and rapid method for analysis of
      interferon alpha (alpha-IFN) in human serum samples. A typical "sandwich type"
      immunoassay was used. Reaction of o-phenylenediamine (OPD) with hydrogen peroxide
      (H(2)O(2)), catalyzed by HRP, produced 2,3-diaminophenazine (PDA), which was
      detected by chemiluminescence imaging analysis with the bis(2,4,6
      trichlorophenyl)oxalate (TCPO)-H(2)O(2)-glyoxaline-PDA chemiluminescent system.
      The TCPO chemiluminescent imaging system is more sensitive and the
      chemiluminescence quantum yield is at least five times higher than for the
      luminol-H(2)O(2)-HRP-PIP (p-iodophenol) chemiluminescent imaging system. The
      results showed there was a very good linear correlation between response and
      amount of alpha-IFN in the range 1.3-156.0 pg mL(-1) (R = 0.9991) and the
      detection limit was 0.8 pg mL(-1) (S/N=3). The relative standard deviation (n =
      9) was 4.7%. The proposed method has been used for successful analysis of the
      amount of alpha-IFN in human serum. The results obtained compared well with those
      obtained by conventional colorimetric ELISA and luminol chemiluminescent ELISA.

PMID- 17211593
TI  - Silicone rod extraction of pharmaceuticals from water.
AB  - Silicone elastomer (in the form of a flexible rod) is one of the materials
      currently tested for use in analytical extraction techniques and passive sampling
      devices. We investigated the applicability of this material for the enrichment of
      selected polar pharmaceuticals (antipyrine, carbamazepine, diclofenac, ibuprofen,
      bezafibrate) from water. Time-resolved batch extraction tests (up to five weeks
      in duration) were performed in stirred water samples ( approximately 0.5 L) with
      2-cm-long silicone rod pieces. After re-extraction of trapped compounds with
      methanol, analysis was performed using liquid chromatography coupled with mass
      spectrometry. Distribution equilibrium was reached after a test duration of seven
      days. The silicone rod/water partition coefficients of the investigated
      pharmaceuticals range from 4 (antipyrine) to 1250 (diclofenac), and are related
      to the hydrophobicity of the compound. Enrichment of these pharmaceuticals in the
      silicone rod is lower than for other compound classes (chlorinated and polycyclic
      hydrocarbons).

PMID- 17211595
TI  - Determination, by inductively coupled plasma mass spectrometry, of changes in
      cellular metal content resulting from herpes simplex virus-1 (HSV-1) infection.
AB  - Metals and metal-containing compounds are known to play important roles in many
      biological processes, including metabolic and detoxification pathways and the
      formation and function of proteins. Like all organisms, viruses are expected to
      contain different metals. These metals, either by themselves or in the form of
      metalloproteins, may be involved in the virus's ability to infect healthy cells
      and replicate within them. Identification and speciation of metals in control
      cells and in cells affected by a virus could be helpful in elucidating infection
      and replication mechanisms; these might, in turn, be vital to the development of
      more effective treatments. There has, however, been no extensive investigation of
      the metals specific viruses contain or affect. The objective of this study was to
      investigate changes in cellular metal content resulting from herpes simplex virus
      1 (HSV-1) infection. Inductively coupled plasma mass spectrometry was used to
      identify differences between metal concentrations in uninfected and HSV-1
      infected mammalian cells. Although it can be assumed that decreases in metal
      content are a result of cellular response to the virus, increases can be
      attributed either to cellular response or to the HSV-1 virus itself. Microwave
      digestion and flow injection methods suitable for small sample volumes were used,
      and the effects of different virus inactivation procedures were explored. This
      work is the first step in the identification of metals pertinent to HSV-1
      infection and lays the foundation for future studies concentrating on
      characterization of these metal-associated or containing molecules.

PMID- 17211596
TI  - Single eye analysis and contralateral eye comparison of tear proteins in normal
      and dry eye model rabbits by MALDI-ToF mass spectrometry using wax-coated target
      plates.
AB  - A study of rabbit tear protein expression in a dry eye rabbit model was performed
      to determine if a pattern in expressed proteins could be identified. The
      uniqueness of the model allows the comparison of normal (control) eye tear
      protein expression with surgically induced dry eye tear protein expression in
      individual animals. The sensitivity of the method allows for single eye analysis.
      One-dimensional mini-gel electrophoresis of the tear proteins did not show
      substantial differences between band patterns of the normal versus the dry eye,
      but was used to assess the molecular weight ranges of the major proteins.
      Specific assignments of some of the predominant proteins were obtained by tandem
      mass spectrometry (MS) which showed that the lower molecular weight lipid-binding
      proteins (approximately 10 kDa to 36 kDa) constitute a considerable amount of the
      observed protein, followed in lesser quantities by the transferrins which have
      higher molecular weights ranging from 70 kDa to 85 kDa. Enhancement of matrix
      assisted laser desorption/ionization time-of-flight (MALDI-ToF) MS linear mode
      analysis of intact proteins in tear fluid was demonstrated through the use of wax
      coated MALDI plates and spot washing. MALDI-ToF MS analysis of the expressed tear
      proteins illustrates that differences between normal eye tear and dry eye tear
      protein content are manifested in changes in the lower molecular weight lipid
      binding proteins such as lipophilin which exhibits an increase in concentration
      in the dry eye, and beta-2 microglobulin which undergoes a decrease.

PMID- 17211597
TI  - Assessment of priority pesticides, degradation products, and pesticide adjuvants
      in groundwaters and top soils from agricultural areas of the Ebro river basin.
AB  - Gas chromatography-mass spectrometry (GC/MS) was employed for the determination
      of 30 widely used pesticides including various transformation products and
      alkylphenols in water and agricultural soils with the aim of assessing the impact
      of these compounds in agricultural soils and the underlying aquifer. The
      extraction, clean-up, and analytical procedures were optimized for both water and
      soil samples to provide a highly robust method capable of determining target
      analytes at the ppb-ppt level with high precision. For water samples, different
      solid-phase extraction cartridges and conditions were optimized; similarly,
      pressurized liquid extraction conditions were tested to provide interference-free
      extracts and high sensitivity. Instrumental LODs of 3-4 pg were obtained. The
      multi-residue extraction procedures were applied to the analysis of groundwaters
      and agricultural soils from the Ebro river basin (NE Spain). Most ubiquitous
      herbicides detected were triazines but some acetanilides and organophosphorus
      pesticides were also found; the pesticide additive tributylphosphate was found in
      all water samples. Levels varied between 0.57 and 5.37 microg/L in groundwater,
      whereas nonylphenol was the sole compound detected in soil. Alkylphenols are used
      as adjuvants in pesticide formulations and are present in sludges employed as
      soil fertilizers. Occurrence was found to be similar to other environmental
      studies.

PMID- 17211598
TI  - [An improved vertebral body replacement for the thoracolumbar spine. A
      biomechanical in vitro test on human lumbar vertebral bodies].
AB  - BACKGROUND: In recent years, the use of expandable titanium cages for vertebral
      body replacement in the thoracolumbar spine has been well established for the
      treatment of tumors, unstable traumatic lesions, or posttraumatic deformity.
      Collapse of the implant into the vertebral body remains a point of concern. A
      biomechanical compression test was designed to assess implant subsidence for a
      newly developed prototype for vertebral body replacement in the thoracolumbar
      spine using human cadaveric lumbar vertebrae. The objective of this study was to
      compare the compressive performance of a new expandable cage with modified end
      plate design with three commonly available expandable cages for vertebral body
      replacement. MATERIALS AND METHODS: The compressive strengths at the implant
      vertebral body interface were measured via axial loading of the new prototype
      (Synex II) in comparison with three different expandable titanium cages: Synex I
      (Synthes), Obelisc (Ulrich Medical) and X-Tenz (DePuy Spine). Twenty-four intact,
      fresh frozen human lumbar vertebrae (L1-L4) were distributed into four identical
      groups according to BMD (determined by quantitative computed tomography) and the
      vertebral level. Specimens were loaded in the craniocaudal direction with a
      material testing machine at a constant speed of 5 mm/min. Load displacement
      curves were continuously recorded for each specimen until failure (diminishment
      of compressive force (F)/obvious implant migration through the vertebral body
      endplate). One-way analysis of variance and post-hoc tests (Bonferroni) were
      applied to detect differences at 1, 2, 3, 4 mm displacement (F1-4 mm), and Fmax
      between implant groups. RESULTS: The four expandable cages did not show
      statistically significant biomechanical differences in terms of maximum
      compression force (Fmax) until failure: Synex II (1,782 N/4.7 mm); Synex I (1,645
      N/4.7 mm); Obelisc (1,314 N/4.2 mm); X-Tenz (1,470 N/6.9 mm). However, the mean
      compression force until 4 mm displacement (F1-4 mm: 300-1,600 N) was highest for
      Synex II. The difference at 2 mm displacement was significant (p=0.028) between
      Synex II (F2 mm=879 N) and X-Tenz (F2 mm=339 N). CONCLUSION: The modified
      endplate design of the new prototype was found to improve its compressive
      performance under constrained uniaxial loading conditions at the implant-bone
      interface. The improved compressive behaviour of the new implant might help to
      reduce the risk of implant subsidence and collapse into the vertebral body in
      vivo.

PMID- 17211599
TI  - [Indications and techniques for wrist arthroscopy].
AB  - After considering the anatomy of the wrist, the technical requirements for wrist
      arthroscopy are discussed. This method is used as an additional diagnostic
      procedure and staging procedure as well as a therapeutic technique.
      Complications, which are rare, most commonly involve nerve irritation, damage to
      cutaneous nerves and extensor tendons. Lose bodies can be removed
      arthroscopically, however, arthroscopically assisted fracture treatment or the
      removal of ganglions are uncommon. Approaches are lateral and oriented on the
      extensor tendons or other anatomical landmarks. Arthroscopy is especially useful
      by carpal instability as it offers many possibilities, not only diagnostically
      but also therapeutically.

PMID- 17211600
TI  - Stimulation of catecholamine synthesis via activation of p44/42 MAPK in cultured
      bovine adrenal medullary cells by milnacipran.
AB  - Milnacipran is a serotonin noradrenaline reuptake inhibitor (SNRI) and is used
      clinically as an antidepressant. We report here the effect of milnacipran on
      catecholamine synthesis in cultured bovine adrenal medullary cells. Incubation of
      adrenal medullary cells with milnacipran (300 ng/ml, 1,065 nM) for 20 min
      resulted in a significant increase in 14C-catecholamine synthesis from
      [14C]tyrosine, but not from [14C]DOPA, whereas the selective serotonin reuptake
      inhibitors (SSRIs), paroxetine (300 ng/ml, 800 nM) and fluvoxamine (300 ng/ml,
      691 nM), had little effect. Milnacipran, but not paroxetine or fluvoxamine,
      increased the activity of tyrosine hydroxylase, the rate-limiting step of
      catecholamine biosynthesis, in a concentration-dependent manner (100-300 ng/ml,
      355-1,065 nM). U0126 (1 microM), an inhibitor of p44/42 mitogen-activated protein
      kinase (MAPK) kinase, abolished the stimulatory effects of milnacipran on
      tyrosine hydroxylase activity. Furthermore, incubation of cells with milnacipran
      (30-100 ng/ml) for 5 min activated p44/42 MAPK, whereas paroxetine and
      fluvoxamine did not. The present findings suggest that milnacipran activates
      tyrosine hydroxylase and then stimulates catecholamine synthesis through a p44/42
      MAPK-dependent pathway in cultured bovine adrenal medullary cells.

PMID- 17211602
TI  - Parapharyngeal space lymphadenopathy.
AB  - Parapharyngeal space masses are rare in the pediatric population and have a
      higher incidence of malignancy than those in adults, although the differential
      diagnosis is similar. We present the work-up and treatment of a child with a
      parapharyngeal space mass discovered incidentally on CT imaging.

PMID- 17211603
TI  - Osteochondromas and growth retardation secondary to externally or internally
      administered radiation in childhood.
AB  - For over five decades, osteochondromas (exostoses) and associated growth
      retardation have been known to be caused by radiation damage to the growing
      skeleton. Patients can be divided into three exposure groups. Group I received
      external beam radiation therapy primarily for the treatment of childhood cancers
      (typical dose 3,500 cGy), and 6-20% developed osteochondromas and growth
      retardation within the radiation portal. Group II consists of recently described
      patients who received total body irradiation in preparation for bone marrow
      transplant (typical dose: 800-1,200 cGy), and about 20% developed osteochondromas
      and growth retardation. Group III consists of 206 German children who in the
      1940s and early 1950s received intravenous radioactive Peteosthor (Ra-224) to
      treat bone tuberculosis (estimated typical dose: 1,000-2,000 cGy), and 14%
      developed osteochondromas and growth retardation, among other benign and
      malignant sequelae. Combining these three exposure groups, osteochondromas and
      growth retardation develop in at least 6-20% of children who receive therapeutic
      radiation to their growing skeletons.

PMID- 17211601
TI  - Tools to study beta3-adrenoceptors.
AB  - Beta(3)-adrenoceptors mediate some of the effects of catecholamines on tissues
      such as blood vessels or the urinary bladder and are putative targets for the
      treatment of diseases such as the overactive bladder syndrome. Progress in the
      understanding of the presence, function, and regulation of beta(3)-adrenoceptors
      has been hampered by a lack of highly specific tools. "Classical" beta(3)
      adrenoceptor agonists such as BRL 37,344 [(R*, R*)-(+/-)-4[2-[(3-chlorophenyl)-2
      hydroxyethyl) amino] propyl] phenoxyacetic acid] and CGP 12,177 [(+/-)-4-(3-t
      butylamino-2-hydroxypropoxy)benzimidazol-2-one] are only partial agonists in many
      settings, have limited selectivity over other beta-adrenoceptor subtypes, and may
      additionally act on receptors other than beta-adrenoceptors. More efficacious and
      more selective agonists have been reported and, in some cases, are in clinical
      development but are not widely available for experimental studies. The widely
      used antagonist SR 59,230 [3-(2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1
      ylamino]-2S-2-propanoloxalate] is not selective for beta(3)-adrenoceptors, at
      least in humans, and may actually be a partial agonist. Radioligands, which are
      suitable either for the selective labeling of beta(3)-adrenoceptors or for the
      nonselective labeling of all beta-adrenoceptor subtypes, are also missing.
      beta(3)- and beta(1)/beta(2) double knockout mice have been reported, but their
      usefulness for extrapolations in humans is questionable based upon major
      differences between humans and rodents with regard to the ligand recognition and
      expression profiles of beta(3)-adrenoceptors. While the common availability of
      more selective agonists and antagonists at the beta(3)-adrenoceptor is urgently
      awaited, the limitations of the currently available tools need to be considered
      in studies of beta(3)-adrenoceptor for the time being.

PMID- 17211604
TI  - Diagnosis of aortic coarctation by tardus-parvus renal artery Doppler signal in
      an infant with multicystic dysplastic kidney: a case report.
AB  - We report an infant with known unilateral multicystic dysplastic kidney (MCDK)
      who underwent renal ultrasonography and Doppler spectral waveform analysis for
      investigation of hypertension. A tardus-parvus waveform was demonstrated in the
      renal artery on the normal side suggesting either renal artery or more proximal
      stenosis. Coarctation of the aorta was subsequently demonstrated.

PMID- 17211605
TI  - Incidence, microbiological findings, and clinical presentation of sternal wound
      infections after cardiac surgery with and without local gentamicin prophylaxis.
AB  - Sternal wound infection (SWI) is a serious complication after cardiac surgery. In
      a previous randomized controlled trial, the addition of local collagen-gentamicin
      in the sternal wound before wound closure was found to significantly reduce the
      incidence of postoperative wound infections compared with the routine intravenous
      prophylaxis of isoxazolyl-penicillin only. The aims of the present study were to
      analyse the microbiological findings of the SWIs from the previous trial as well
      as to correlate these findings with the clinical presentation of SWI. Differences
      in clinical presentation of SWIs, depending on the causative agent, could be
      identified. Most infections had a late, insidious onset, and the majority of
      these were caused by staphylococci, predominantly coagulase-negative
      staphylococci. The clinically most fulminant infections were caused by gram
      negative bacteria and presented early after surgery. Local administration of
      gentamicin reduced the incidence of SWIs caused by all major, clinically
      important bacterial species. Propionibacterium acnes was identified as a possible
      cause of SWI and may be linked to instability in the sternal fixation. There was
      no indication of an increase in the occurrence of gentamicin-resistant bacterial
      isolates in the treatment group. Furthermore, the addition of local collagen
      gentamicin reduced the incidence of SWIs caused by methicillin-resistant
      coagulase-negative staphylococci. This technique warrants further evaluation as
      an alternative to prophylactic vancomycin in settings with a high prevalence of
      methicillin-resistant Staphylococcus aureus.

PMID- 17211606
TI  - Evaluation of three rapid assays for detection of Clostridium difficile toxin A
      and toxin B in stool specimens.
AB  - Diagnosis of Clostridium difficile-associated disease continues to be difficult
      for clinical microbiology laboratories. The aim of this study was to evaluate the
      performance of three enzyme immunoassays for detection of C. difficile toxins A
      and B: the recently marketed rapid enzyme immunoassay Ridascreen Clostridium
      difficile Toxin A/B (R-Biopharm, Darmstadt, Germany) and two established enzyme
      immunoassays, the C. difficile Tox A/B II Assay (TechLab, Blacksburg, VA, USA)
      and the ProSpecT C. difficile Toxin A/B Microplate Assay (Remel, Lenexa, KS,
      USA). Stool specimens (n = 383) from patients with a clinical diagnosis of
      antibiotic-associated diarrhea were examined by these three enzyme immunoassays
      and were additionally cultured for C. difficile on selective agar. Samples giving
      discordant enzyme immunoassay results underwent confirmatory testing by tissue
      culture cytotoxin B assay and by PCR for toxin A (tcdA) and toxin B (tcdB) genes
      from C. difficile. Using the criteria adopted for this study, 60 (15.7%) samples
      tested positive for toxins A and/or B. Sensitivity and specificity of the enzyme
      immunoassays were, respectively, 88.3 and 100% for the TechLab enzyme
      immunoassay, 91.7 and 100% for the R-Biopharm enzyme immunoassay, and 93.3 and
      100% for the Remel enzyme immunoassay. The differences between these results are
      statistically not significant (p > 0.05). The results show that all three enzyme
      immunoassays are acceptable tests for the detection of C. difficile toxins A and
      B directly in fecal specimens or in toxigenic cultures.

PMID- 17211607
TI  - Complicating infectious foci in patients with Staphylococcus aureus or
      Streptococcus species bacteraemia.
AB  - Complicating infectious foci resulting from haematogenous or local spread of
      microorganisms are observed frequently in patients with Staphylococcus aureus
      bacteraemia (SAB) or Streptococcus species bacteraemia (SSB). The aim of this
      study was to compare the epidemiology of complicating infectious foci during SAB
      and SSB in a university hospital in The Netherlands. The charts of all adult
      patients diagnosed with SAB or SSB (except for Streptococcus pneumoniae
      bacteraemia) from July 2002 until December 2004 were reviewed retrospectively.
      Overall, 180 immunocompetent patients were identified, 127 with SAB and 53 with
      SSB. The percentage of patients with complicating infectious foci (39% of SAB
      patients, 25% of SSB patients) did not differ significantly between the groups.
      Endocarditis and cerebral involvement, however, were significantly more common in
      the SSB group. Of all complicating infectious foci, 32% lacked guiding signs or
      symptoms and 10% were detected only at autopsy. Factors associated with the
      development of complicating infectious foci were a delay in treatment for more
      than 48 h after the onset of symptoms, community acquisition, persistently
      positive blood cultures, congenital heart disease, and the presence of foreign
      bodies or prosthetic valves. Infection-related mortality was 18% in SAB patients
      and 11% in SSB patients and was significantly higher in patients with
      complicating infectious foci (29 vs. 9%). In conclusion, complicating infectious
      foci develop in approximately one-third of all patients with SAB and SSB. An
      active approach that entails searching for the complicating infectious foci is
      warranted in these patients, because only two-thirds of complicated infectious
      foci have guiding symptoms or signs, and infection-related mortality is
      significantly increased in patients with complicating infectious foci compared to
      patients without these infections.

PMID- 17211608
TI  - APOA5 gene variation modulates the effects of dietary fat intake on body mass
      index and obesity risk in the Framingham Heart Study.
AB  - Diet is an important environmental factor interacting with our genes to modulate
      the likelihood of developing lipid disorders and, consequently, cardiovascular
      disease risk. Our objective was to study whether dietary intake modulates the
      association between APOA5 gene variation and body weight in a large population
      based study. Specifically, we have examined the interaction between the APOA5
      1131T>C and 56C>G (S19W) polymorphisms and the macronutrient intake (total fat,
      carbohydrate, and protein) in their relation to the body mass index (BMI) and
      obesity risk in 1,073 men and 1,207 women participating in the Framingham
      Offspring Study. We found a consistent and statistically significant interaction
      between the -1131T>C single-nucleotide polymorphism (SNP; but not the 56C>G) and
      total fat intake for BMI. This interaction was dose-dependent, and no
      statistically significant heterogeneity by gender was detected. In subjects
      homozygous for the -1131T major allele, BMI increased as total fat intake
      increased. Conversely, this increase was not present in carriers of the -1131C
      minor allele. Accordingly, we found significant interactions in determining
      obesity and overweight risks. APOA5-1131C minor allele carriers had a lower
      obesity risk (OR, 0.61, 95%; CI, 0.39-0.98; P = 0.032) and overweight risk (OR,
      0.63, 95%; CI, 0.41-0.96; P = 0.031) compared with TT subjects in the high fat
      intake group (>or=30% of energy ) but not when fat intake was low (OR, 1.16, 95%;
      CI, 0.77-1.74; P = 0.47 and OR = 1.15, 95%; CI, 0.77-1.71; P = 0.48) for obesity
      and overweight, respectively). When specific fatty acid groups were analyzed,
      monounsaturated fatty acids showed the highest statistical significance for these
      interactions. In conclusion, the APOA5-1131T>C SNP, which is present in
      approximately 13% of this population, modulates the effect of fat intake on BMI
      and obesity risk in both men and women.

PMID- 17211610
TI  - Copper and clioquinol treatment in young APP transgenic and wild-type mice:
      effects on life expectancy, body weight, and metal-ion levels.
AB  - There is mounting evidence that the amyloid precursor protein (APP), the key
      protein in Alzheimer's disease (AD) is involved in the copper (Cu) homeostasis in
      the brain. Conflicting results about the potential use of dietary Cu and
      clioquinol (CQ), a known Cu chelator, have been reported using APP transgenic
      mice. Previously, in vitro studies have demonstrated that CQ can act as a Cu
      transporter. To analyze the potential function of CQ as a Cu transporter in vivo,
      the nutritional effect of Cu and CQ was analyzed in young APP transgenic mice and
      nontransgenics with food pellets containing either Cu, CQ, Cu plus CQ (Cu + CQ),
      or without addition of supplements (control). The offspring were fed with
      corresponding food pellets until the age of 14 weeks. We observed an increased
      lethality of APP transgenics upon CQ treatment, which could be rescued by a co
      treatment with Cu. The exposure of Cu + CQ led to a modest but significant
      increase in cerebral Cu levels, most likely due to an enhanced transport of CQ-Cu
      complexes. In CQ or Cu + CQ treatment groups, the plasma levels of Cu, zinc, and
      iron were reduced in all animals; moreover, Cu treatment alone reduced only
      plasma iron levels. We conclude not only that CQ has certain toxicity but also
      that the chelating effect, perhaps, plays a secondary role with respect to its
      properties as an intracellular Cu transporter, thus, counteracting the supposed
      therapeutic effects of CQ as an agent for chelating therapy in AD.

PMID- 17211611
TI  - A novel locus for autosomal recessive nonsyndromic hearing impairment, DFNB63,
      maps to chromosome 11q13.2-q13.4.
AB  - Hereditary hearing impairment is a genetically heterogeneous disorder. To date,
      49 autosomal recessive nonsyndromic hearing impairment (ARNSHI) loci have been
      described, and there are more than 16 additional loci announced. In 25 of the
      known loci, causative genes have been identified. A genome scan and fine mapping
      revealed a novel locus for ARNSHI (DFNB63) on chromosome 11q13.2-q13.4 in a five
      generation Turkish family (TR57). The homozygous linkage interval is flanked by
      the markers D11S1337 and D11S2371 and spans a 5.3-Mb interval. A maximum two
      point log of odds score of 6.27 at a recombination fraction of theta = 0.0 was
      calculated for the marker D11S4139. DFNB63 represents the eighth ARNSHI locus
      mapped to chromosome 11, and about 3.33 Mb separate the DFNB63 region from MYO7A
      (DFNB2/DFNB11). Sequencing of coding regions and exon-intron boundaries of 13
      candidate genes, namely SHANK2, CTTN, TPCN2, FGF3, FGF4, FGF19, FCHSD2, PHR1,
      TMEM16A, RAB6A, MYEOV, P2RY2 and KIAA0280, in genomic DNA from an affected
      individual of family TR57 revealed no disease-causing mutations.

PMID- 17211612
TI  - An unexpected new role of mutant Ras: perturbation of human embryonic
      development.
AB  - The Ras signaling pathway controls important cellular responses to growth
      factors, and somatic mutations in RAS genes and other components of the Ras
      pathway, such as PTPN11 (encoding the protein-tyrosine phosphatase SHP-2) and
      BRAF, are found in human malignancies. Ras proteins are guanosine nucleotide
      binding proteins that cycle between active guanosine triphosphate (GTP)-bound and
      inactive guanosine diphosphate (GDP)-bound conformations. Neoplasia-associated
      Ras mutations frequently affect amino acids G12, G13, or Q61 and decrease the
      intrinsic guanosine triphosphatase (GTPase) activity by ten- to twentyfold. The
      GTPase activity is crucial for Ras inactivation by hydrolysis and release of a
      phosphate group from Ras.GTP to produce Ras.GDP. We and others have recently
      discovered germline mutations in the KRAS gene in individuals diagnosed with
      Noonan and cardio-facio-cutaneous (CFC) syndrome, two clinically overlapping
      disorders characterized by short stature, distinct facial anomalies, heart
      defects, and other abnormalities. Noonan syndrome-associated mutations V14I and
      T58I K-Ras activate Ras but have milder biochemical effects than somatic
      mutations encountered in cancers, offering an explanation why these K-Ras lesions
      are tolerated during embryonic development. Together with recent findings of
      BRAF, MEK1, and MEK2 mutations in CFC syndrome and HRAS mutations in Costello
      syndrome, another clinically related disorder, it has now become clear that
      Noonan-like features (short stature, relative macrocephaly, facial anomalies,
      learning difficulties) that are found in these three related disorders are a
      result of constitutive activation of the Ras-Raf-extracellular signal-regulated
      and mitogen-activated protein kinase pathway.

PMID- 17211613
TI  - [Surgery of the parapharyngeal adenomas].
AB  - Pleomorphic adenomas are the most common tumors of the parapharyngeal space (PPS)
      and often grow to an enormous size before becoming visible or symptomatic. CT and
      MRI scans are important in both diagnosis and surgical treatment. There are
      basically four different surgical approaches (transoral-transpalatal,
      transcervical-submandibular, transparotid und transmandibular) to the anterior
      PPS. Wide and direct exposure of the PPS is provided by a midline mandibulotomy
      with transection of the floor of the mouth. Owing to its morbidity this approach
      is reserved exclusively for extended tumors. The transcervical-submandibular
      route with blunt finger dissection generally offers adequate access for total
      tumor removal. For adenomas arising from the parotid gland a transparotid
      approach may be utilized. Adenomas located medially are better be resected
      transorally by splitting the soft palate.

PMID- 17211614
TI  - [Auditory processing disorders : Consensus statement by the German Society for
      Phoniatry and Paedaudiology].
AB  - The consensus statement published by the German Society for Phoniatry and
      Paedaudiology in the year 2000 has been revised and actualized. The revised
      version takes into account current scientific and clinical findings. Aspects of
      the definition of auditory processing disorders (APD) are described extensively.
      These include symptoms, anamnestic information and diagnostic steps (preliminary
      examinations, subjective and objective audiological procedures). APD can appear
      in different forms, some of which can be classified within subtypes. Furthermore,
      factors which need to be considered in order to differentiate between APD and
      other diseases are specified. Therapeutic intervention possibilities which are
      rated according to their prognostic values conclude the article.

PMID- 17211615
TI  - [Practicability of a surgical multilevel therapy in patients with obstructive
      sleep apnea].
AB  - BACKGROUND: Obstructive sleep apnea syndrome is a "systemic disease" of the upper
      airways and the upper digestive tract. The concept of multilevel surgery takes
      account of the fact that the location of the obstruction frequently cannot be
      identified precisely. PATIENTS AND METHODS: In this retrospective study over 4
      years, data on 25 patients (median age 49.9 years) with moderate to severe OSAS
      treated with a surgical multilevel therapy were statistically evaluated. The
      treatment carried out consisted in reduction of the inferior turbinate, if
      necessary combined with septum plasty, and conventional uvulopalatopharyngoplasty
      (UPPP), combined with tonsillectomy and radiofrequency therapy of the base of the
      tongue if appropriate. Pre- and postoperative clinical and polysomnographical
      checks were performed. RESULTS: The mean apnea-hypopnea index (AHI) was 39.2+/
      19.7/h before surgery. Postoperatively a highly significant reduction of AHI to
      16.5+/-9.9/h (p<0.0001) was seen. In 13 out of 25 patients (52%) the disease was
      cured (AHI<20 and 50% reduction). In 23 patients the AHI improved. In 15 patients
      AHI was reduced by more than 50%. CONCLUSION: Multilevel surgery should be
      considered as an alternative for patients suffering from OSAS, especially in view
      of the poor long-term results in patients who receive CPAP therapy or are
      intolerant to CPAP.

PMID- 17211616
TI  - A biomechanical model of mammographic compressions.
AB  - A number of biomechanical models have been proposed to improve nonrigid
      registration techniques for multimodal breast image alignment. A deformable
      breast model may also be useful for overcoming difficulties in interpreting 2D X
      ray projections (mammograms) of 3D volumes (breast tissues). If a deformable
      model could accurately predict the shape changes that breasts undergo during
      mammography, then the model could serve to localize suspicious masses (visible in
      mammograms) in the unloaded state, or in any other deformed state required for
      further investigations (such as biopsy or other medical imaging modalities). In
      this paper, we present a validation study that was conducted in order to develop
      a biomechanical model based on the well-established theory of continuum mechanics
      (finite elasticity theory with contact mechanics) and demonstrate its use for
      this application. Experimental studies using gel phantoms were conducted to test
      the accuracy in predicting mammographic-like deformations. The material
      properties of the gel phantom were estimated using a nonlinear optimization
      process, which minimized the errors between the experimental and the model
      predicted surface data by adjusting the parameter associated with the neo-Hookean
      constitutive relation. Two compressions (the equivalent of cranio-caudal and
      medio-lateral mammograms) were performed on the phantom, and the corresponding
      deformations were recorded using a MRI scanner. Finite element simulations were
      performed to mimic the experiments using the estimated material properties with
      appropriate boundary conditions. The simulation results matched the experimental
      recordings of the deformed phantom, with a sub-millimeter root-mean-square error
      for each compression state. Having now validated our finite element model of
      breast compression, the next stage is to apply the model to clinical images.

PMID- 17211617
TI  - Congenital mesenteric hernia causing intestinal obstruction in children.
AB  - A mesenteric hernia is one type of intraperitoneal hernia. There is no hernia sac
      in this situation but only a mesenteric defect, which is present at birth.
      Strangulated mesenteric hernia is a rare cause of intestinal obstruction
      especially in the pediatric population. Between January 1996 and January 2006,
      four patients with intestinal obstruction were determined to have congenital
      mesenteric hernia at Chang Gung Children's Hospital. Patients consisted of three
      boys and one girl, ranging in age from 2 years 5 months to 5 years 4 months. All
      patients presented with symptoms and signs indicative of intestinal obstruction.
      On physical examination, all patients appeared to be severely ill. A shock-like
      state was associated with necrosis of the strangulated bowel in two patients. A
      palpable abdominal mass was present in one patient with volvulus of small bowel.
      The plain abdominal radiography and the ultrasound scan also showed dilatation of
      the small bowel and excluded intussusception. All the patients underwent
      laparotomy after initial resuscitation. During laparotomy, three patients had
      incarceration of small bowel through the small mesenteric defect, and another one
      had volvulus with gangrenous bowel entrapped within a large mesenteric defect.
      The defects ranged in size are from 2 to 7 centimeters in diameter. Simple
      reduction of the incarcerated bowel with repair of the defect was performed in
      two patients, resection of gangrenous bowel and primary anastomosis was required
      in one patient, and resection with end ileostomy was needed in another one
      patient. There was no postoperative mortality in our patients. CONCLUSION: A
      mesenteric hernia is a rare cause of intestinal obstruction, especially in
      children. Open exploration is the only way to establish a clear anatomic
      diagnosis.

PMID- 17211618
TI  - Age and sex-related differences in dose-dependent hemodynamic response to
      landiolol hydrochloride during general anesthesia.
AB  - OBJECTIVE: Landiolol hydrochloride is a new ultra-short-acting beta(1)-adrenergic
      receptor blocking agent that is used for patients with tachycardia during general
      anesthesia. The hemodynamic response to a beta-adrenergic receptor blocking agent
      is generally dependent on the subject. In the present investigation we
      investigated the effects of age and sex on the hemodynamic response to different
      doses of landiolol. METHODS: Following a persistence of tachycardia for more than
      1 min, landiolol was infused at 0.03125, 0.0625 and 0.125 mg kg(-1) min(-1) for 1
      min followed by 0.01, 0.02 and 0.04 mg kg(-1)min(-1) for 10 min in groups L, M
      and H, respectively. Heart rate (HR), systolic (sBP) and diastolic blood pressure
      (dBP) were recorded each minute during the procedure. The respective changes were
      evaluated using logistic analysis with the equation Y(t) = p + (q - p)/[1 + exp
      {4m/(q - p))(k - t)}], where p, q, m and k indicate the upper asymptote, lower
      asymptote, maximum slope and time at the maximum slope. RESULTS: Parameters q and
      k for HR in group H were smaller than those in group L, whereas the parameters
      for sBP and dBP were unchanged among the three groups. Parameter q for HR in
      group H decreased with age of the patient. There was no significant difference in
      the landiolol-induced change in HR between males and females. CONCLUSION: The
      hemodynamic response to landiolol is reliably modeled by the logistic function,
      especially in terms of HR. Landiolol causes a rapid and dose-dependent decrease
      in HR, whereas landiolol-induced changes in sBP and dBP are independent of dose.
      The landiolol-induced decrease in HR becomes larger with aging, but shows no sex
      difference. The logistic model may be useful for studying hemodynamic responses
      to landiolol based on age and sex differences, and may allow development of an
      improved monitoring system. IMPLICATION STATEMENT: The logistic function reliably
      represents the hemodynamic responses to landiolol. Landiolol reduces HR rapidly
      and in a dose-dependent manner whereas landiolol-induced changes in sBP and dBP
      are independent of dose. A larger decrease in HR is caused by landiolol in
      elderly patients, but there is no sex difference in the landiolol-induced change
      in HR.

PMID- 17211619
TI  - Influence of UGT1A8 and UGT2B7 genetic polymorphisms on mycophenolic acid
      pharmacokinetics in Japanese renal transplant recipients.
AB  - OBJECTIVE: UGT1A8 and UGT2B7 are important uridine diphosphate
      glucuronosyltransferase isoforms for the glucuronidation of mycophenolic acid
      (MPA). The aim of this investigation was to elucidate MPA pharmacokinetics in
      UGT1A8 and UGT2B7 genotypes in Japanese renal transplant recipients. METHODS:
      Seventy-two recipients received repeated doses of mycophenolate mofetil and
      tacrolimus. On day 28 after renal transplantation, plasma MPA concentrations were
      measured for the next 24 h using high-performance liquid chromatography. UGT1A8*2
      (A(173)G) and UGT2B7*2 (Y(268)) were detected using a PCR-RFLP-based procedure.
      RESULTS: There were no significant differences in daytime and nighttime
      pharmacokinetics of MPA between UGT1A8 or UGT2B7 genotypes. The mean daytime dose
      adjusted AUC(0-12) of MPA in UGT1A8*1/*1, *1/*2 and *2/*2 were 2.47, 2.33 and
      2.57 ng.h/ml/mg/kg (P = 0.7711), and the mean nighttime AUC(0-12) were 2.15, 2.00
      and 2.08 ng.h/ml/mg/kg (P = 0.4656). The mean daytime and nighttime dose-adjusted
      AUC(0-12) of MPA in UGT2B7*1/*1, *1/*2 and *2/*2 were 2.61, 2.24 and 2.03
      ng.h/ml/mg/kg and 2.18, 1.94, and 1.45 ng.h/ml/mg/kg, respectively (P = 0.3475
      and 0.2575). The mean nighttime C(max), t(max), and AUC(6-12)/AUC(0-12) ratio
      (enterohepatic circulation and recirculation ratio) of MPA in all UGT1A8 and
      UGT2B7 genotypes were lower, longer, and higher, respectively, than the daytime
      values. CONCLUSIONS: Both UGT1A8 and UGT2B7 allelic variants seem not to affect
      Japanese interindividual variability for plasma MPA concentration. Regardless of
      UGT1A8 and UGT2B7 genetic polymorphisms, the absorption of MPA through
      enterohepatic recirculation is higher at night.

PMID- 17211620
TI  - Factors associated with adherence to drug therapy: a population-based study.
AB  - OBJECTIVE: To investigate adherence to prescription in a female population aged
      35-65 years. DESIGN: Postal questionnaire study of 2991 randomly sampled 35- to
      64-year-old women in seven provinces of central Sweden. METHODS: The study was
      performed in 1995 as a cross-sectional postal questionnaire study in seven
      counties in central Sweden. The questionnaire was sent to a random sample of 4200
      women between the ages of 35 and 64, of whom 2991 (71.2%) responded. The
      questionnaire asked about drugs prescribed during the past year and about factors
      potentially affecting adherence. RESULTS: The same women had different degrees of
      adherence to different medications. A large number of factors were associated
      with adherence. Multivariate analysis revealed that age, scheduled check-up,
      perceived importance of medication, concerns about medication safety and taking
      medication for a respiratory or a cardiovascular disease were significantly
      related to adherence. Adherence ranged from 15-98% depending on these factors,
      and was the lowest among young women who regarded their medication as unimportant
      and who had no scheduled check-up; the highest reported adherence was found among
      elderly women who regarded their medication as important and who had a scheduled
      check-up. CONCLUSION: Factors that were associated with the perceived importance
      of medication had a positive effect on adherence, while concerns about medication
      safety had a negative effect.

PMID- 17211621
TI  - Conformational change of influenza virus hemagglutinin is sensitive to ionic
      concentration.
AB  - The homotrimeric spike glycoprotein hemagglutinin (HA) of influenza virus
      undergoes a low pH-mediated conformational change which mediates the fusion of
      the viral envelope with the target membrane. Previous approaches predict that the
      interplay of electrostatic interactions between and within HA subunits, HA 1 and
      HA2, are essential for the metastability of the HA ectodomain. Here, we show that
      suspension media of low ionic concentration promote fusion of fluorescent
      labelled influenza virus X31 with erythrocyte ghosts and with ganglioside
      containing liposomes. By measuring the low pH mediated inactivation of the fusion
      competence of HA and the Proteinase K sensitivity of low pH incubated HA we show
      that the conformational change is promoted by low ionic concentration. We surmise
      that electrostatic attraction within the HA ectodomain is weakened by lowering
      the ionic concentration facilitating the conformational change at low pH.

PMID- 17211622
TI  - Multi drug resistance-dependent "vacuum cleaner" functionality potentially driven
      by the interactions between endocytosis, drug size and Pgp-like transporters
      surface density.
AB  - In cells, multi drug resistance (MDR) is associated with Pgp-like transporters
      expression extruding drugs from cellular membranes. MDR is efficiently generated
      with a relatively small fraction of membrane transporters. As the insertion of
      drugs into cellular membranes is widespread, there are no reasons why a drug
      should incorporate the membrane in the vicinity of a transporter. As a result a
      further elusive hypothesis is usually invoked: these transporters act like
      "vacuum cleaners" of drugs embedded in the membrane. Nonetheless, how these
      transporters attract drugs remains obscure. To clarify the "vacuum cleaner"
      notion, we suggest that during its residency time in cellular membranes, the
      lateral movement of drugs from their point of insertion to transporters is
      governed by Brownian's diffusion, which allows the drugs/transporters
      interaction. Taking into account the functionality of Pgp-like transporters,
      namely the extrusion of drugs from the plasma membrane inner leaflet, we
      characterize how the state of drug resistance is triggered involving: membrane
      endocytosis, drug physico-chemical properties and the surface density of Pgp-like
      transporters. In addition, the theory developed provides for the first time a
      theoretical proof of Lipinski's second rule with regard to drugs' size (or MW)
      selectivity on their permeation across cellular membranes.

PMID- 17211623
TI  - Rejection of injectable silicone "Bioplastique" used for vocal fold augmentation.
AB  - A rare case of repeated granulomatous inflammation after silicone injection
      laryngoplasty for vocal fold immobility as well as its treatment by endoscopic
      approach is reported. The patient presented a right-sided vocal fold immobility
      after laryngeal trauma and remained dysphonic despite of logopedic voice therapy
      because of severe glottal insufficiency. An endoscopic transoral intrafold
      silicone injection was applied to improve the vocal function. Silicone granuloma
      inflammation was observed 8 days after the vocal fold augmentation. Oral broad
      spectrum antibiotics and corticosteroids did not improve the inflammation. A
      cordotomy was performed to remove the silicone implant. After 3 months, a second
      endoscopic surgical intervention was necessary to remove a recurrent silicone
      granuloma. Eight months after the second surgical intervention, the inflammation
      had disappeared. An autologous fat injection to restore the glottal closure was
      performed successfully. Type IV contact allergy was excluded with an epicutaneous
      patch and scratch test with components of the silicone implant. Clinical and
      treatment observations are reported and the literature on complications of
      intrafold injected silicone for vocal fold augmentation is reviewed.

PMID- 17211624
TI  - Immunocytochemical localization of glucose 6-phosphatase and cytosolic
      phosphoenolpyruvate carboxykinase in gluconeogenic tissues reveals unsuspected
      metabolic zonation.
AB  - Immunohistochemical analysis was used to define the precise cell-specific
      localization of Glucose-6-phosphatase (Glc6Pase) and cytosolic form of the
      phosphoenolpyruvate carboxykinase (PEPCK-C) in the digestive system (liver, small
      intestine and pancreas) and the kidney. Co-expression of Glc6Pase and PEPCK-C was
      shown to take place in hepatocytes, in proximal tubules of the cortex kidney and
      at the top of the villi of the small intestine suggesting that these tissues are
      all able to perform complete gluconeogenesis. On the other hand, intrahepatic
      bile ducts, collecting tubes of the nephron and the urinary epithelium in the
      calices of the kidney, as well as the crypts of the small intestine, express
      Glc6Pase without significant levels of PEPCK-C. In such cases, the function of
      Glc6Pase could be related to the transepithelial transport of glucose
      characteristic of these tissues, rather than to the neoformation of glucose.
      Lastly, PEPCK-C expression in the absence of Glc6Pase was noted in both the
      exocrine pancreas and the endocrine islets of Langerhans. Possible roles of PEPCK
      C in exocrine pancreas might be the provision of gluconeogenic intermediates for
      further conversion into glucose in the liver, whereas PEPCK-C would be
      instrumental in pyruvate cycling, which has been suggested to play a regulatory
      role in insulin secretion by the beta-cells of the islets.

PMID- 17211625
TI  - Immunohistochemical localization of aromatic L-amino acid decarboxylase in mouse
      taste buds and developing taste papillae.
AB  - Aromatic L-amino acid decarboxylase (AADC) catalyses the decarboxylation of all
      aromatic L-amino acids. In mammals, AADC is expressed in many tissues besides the
      nervous system, and is associated with additional regulatory roles of dopamine
      and serotonin in a wide range of tissues. We examined the expression of AADC by
      using reverse transcription-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. RT-PCR analysis showed that mRNA of AADC was detected in
      the taste bud-containing epithelium of the circumvallate papilla of mice. By
      immunohistochemical analyses, AADC was detected in a subset of taste bud cells of
      fungiform, foliate, and circumvallate papillae. Double-label studies showed that
      AADC colocalized with serotonin, NCAM, PLCbeta2, and PGP9.5. On the other hand,
      AADC never colocalized with alpha-gustducin. Our results of double staining with
      AADC and taste cell markers indicate that only the type III cells could convert 5
      hydroxytryptophan (5-HTP) to serotonin within taste buds. Taken together with
      previous studies, the properties of the type III cell of taste buds exactly fit
      into the APUD (amine and amine precursor uptake and decarboxylation) cell scheme.
      Furthermore, in the developing circumvallate papilla, AADC are first detected in
      a small number of papillary epithelial cells at E14.5. By E18.5, AADC-positive
      epithelial cells also express PGP9.5, which is one of marker of taste cells, and
      these cells have been contacted by developing nerve fibers. These results suggest
      that AADC expression begins at early stages of taste bud cell differentiation,
      and biogenic amines may act on taste bud differentiation of tongue epithelial
      cells, and further may regulate innervation of taste bud progenitor cells.

PMID- 17211627
TI  - Modelling memory functions with recurrent neural networks consisting of input
      compensation units: II. Dynamic situations.
AB  - Modelling the cognitive abilities of humans or animals or building agents that
      are supposed to behave cognitively requires modelling a memory system that is
      able to store and retrieve various contents. The content to be stored is assumed
      to comprise information about more or less invariant environmental objects as
      well as information about movements. A combination of information about both
      objects and movements may be called a situation model. Here we focus, in part, on
      models storing dynamic patterns. In particular, two abilities of humans in
      representing dynamical systems receive special focus: the capability of
      representing the acceleration of objects, as can be found in the movement of a
      pendulum or freely falling objects, and the capability of representing actions of
      transfer, i.e. motion from one point to another, have been modelled using
      recurrent networks consisting of input compensation units. In addition,
      possibilities of combining static and dynamic properties within a single model
      are studied.

PMID- 17211626
TI  - MUC16 in the lacrimal apparatus.
AB  - The aim of the present study was to determine the possible expression of the
      mucin MUC16 in the lacrimal apparatus. Expression and distribution of MUC16 in
      lacrimal gland, accessory lacrimal glands, and nasolacrimal ducts was monitored
      by RT-PCR and immunohistochemistry. MUC16 was expressed and detected in all
      tissues investigated. Comparable to conjunctiva and cornea it was membrane
      anchored in accessory lacrimal glands whereas in lacrimal gland acinar cells and
      columnar cells of the nasolacrimal ducts it was stored in intracytoplasmic
      vesicles without membrane-association. Subepithelial serous glands of the
      nasolacrimal ducts revealed staining of the secretion product. Intracelluar
      production of MUC16 is present in lacrimal gland and epithelial cells of the
      nasolacrimal ducts but it is not clear whether this MUC16 is secreted. MUC16
      seems to be shedded or secreted from the epithelial surface of subepithelial
      serous glands of the nasolacrimal ducts. Our results show that MUC16 is present
      in the whole lacrimal apparatus. Its distribution pattern suggests different
      physiological functions with regard to tear film physiology and tear outflow.
      Moreover, the results demonstrate the existence of so far not recognized
      qualitative differences in the secretion product of main lacrimal gland and
      accessory lacrimal glands (glands of Krause).

PMID- 17211628
TI  - Modelling memory functions with recurrent neural networks consisting of input
      compensation units: I. Static situations.
AB  - Humans are able to form internal representations of the information they process 
      - a capability which enables them to perform many different memory tasks.
      Therefore, the neural system has to learn somehow to represent aspects of the
      environmental situation; this process is assumed to be based on synaptic changes.
      The situations to be represented are various as for example different types of
      static patterns but also dynamic scenes. How are neural networks consisting of
      mutually connected neurons capable of performing such tasks? Here we propose a
      new neuronal structure for artificial neurons. This structure allows one to
      disentangle the dynamics of the recurrent connectivity from the dynamics induced
      by synaptic changes due to the learning processes. The error signal is computed
      locally within the individual neuron. Thus, online learning is possible without
      any additional structures. Recurrent neural networks equipped with these
      computational units cope with different memory tasks. Examples illustrate how
      information is extracted from environmental situations comprising fixed patterns
      to produce sustained activity and to deal with simple algebraic relations.

PMID- 17211629
TI  - Solution behaviour and biological activity of bisamidine complexes of
      platinum(II).
AB  - A series of platinum(II) amidine complexes were previously prepared with the aim
      of obtaining a new class of platinum-based antitumour drugs. This series includes
      compounds of the type cis--[PtCl2{Z-HN=C(NHMe)Me}2] and trans-[PtCl2{Z
      HN=C(NHMe)Me}2] (1, 2), cis-[PtCl2{E-HN=C(NMe2)Me}2] and trans-[PtCl2{E
      HN=C(NMe2)Me}2] (3, 4), cis-[PtCl2{Z-HN=C(NHMe)Ph}2] and trans-[PtCl2{Z
      HN=C(NHMe)Ph}2] (5, 6), and cis-[PtCl2{HN=C(NMe2)Ph}2] and trans
      [PtCl2{HN=C(NMe2)Ph}2] (7, 8). The reactions with dimethyl sulfoxide were studied
      for complexes 5-8; the formation of cationic species containing coordinated
      dimethyl sulfoxide was demonstrated by NMR experiments and electrospray
      ionization mass spectrometry. In this work, the amidine platinum(II) complexes
      were tested for their in vitro cytotoxicity on a panel of various human cancer
      cell lines. The results indicate that the benzamidine complex 8 was the most
      effective derivative also circumventing acquired cisplatin resistance as
      demonstrated by chemosensitivity tests performed on cisplatin-sensitive and
      cisplatin-resistant cell lines. The studies concerning the cellular DNA damage on
      both parental chemosensitive and resistant sublines suggest for the new trans
      amidine complex a different mechanism of action compared with that exhibited by
      cisplatin.

PMID- 17211630
TI  - Gene expression profiling of liver cells after copper overload in vivo and in
      vitro reveals new copper-regulated genes.
AB  - Copper toxicity in the liver is mediated by free-radical generation, resulting in
      oxidative stress. To prevent toxic accumulation of copper, liver cells adapt to
      high copper levels. Here, we used microarray analysis to compare the adaptive
      responses on global gene expression in liver cells exposed to high copper levels
      in vitro and in vivo. In HepG2 cells we identified two clusters of upregulated
      genes over time, an "early" cluster that comprised metallothionein genes and a
      "late" cluster, highly enriched in genes involved in proteasomal degradation and
      in oxidative stress response. Concomitant with the "late" cluster, we detected a
      significant downregulation of several copper metabolism MURR1 domain (COMMD)
      genes that were recently implicated in copper metabolism and inhibition of
      nuclear transcription factor kappaB (NF-kappaB) signaling. As metal-induced
      oxidative stress increases NF-kappaB activity, our data suggest a role for
      reduced COMMD protein levels in prolonged activation of NF-kappaB, thus inducing
      cell survival. Mice exposed to a copper diet that highly exceeded normal daily
      intake accumulated only twofold more hepatic copper than control mice. Although a
      moderate, but significant upregulation of a set of 22 genes involved in immunity,
      iron and cholesterol metabolism was detected, these cannot account for direct
      mechanisms involved in copper excretion. In conclusion, we identified a novel set
      of genes that represent a delayed response to copper overload, thus providing
      insight into the adaptive transcriptional response to copper-induced oxidative
      stress.

PMID- 17211631
TI  - Metal ion binding properties of Triticum [corrected] aestivum Ec-1
      metallothionein: evidence supporting two separate metal thiolate clusters.
AB  - Metallothioneins are ubiquitous low molecular mass, cysteine-rich proteins with
      an extraordinary high metal ion content. In contrast to the situation for the
      vertebrate forms, information regarding the properties of members of the plant
      metallothionein family is still scarce. We present the first spectroscopic
      investigation aiming to elucidate the metal ion binding properties and metal
      thiolate cluster formation of the Triticum [corrected] aestivum (common wheat)
      early cysteine-labeled plant metallothionein (Ec-1). For this, the protein was
      overexpressed recombinantly in Escherichia coli. Recombinant Ec-1 is able to bind
      a total of six divalent d10 metal ions in a metal thiolate cluster arrangement.
      The pH stability of the zinc and cadmium clusters investigated is comparable to
      stabilities found for mammalian metallothioneins. Using cobalt(II) as a
      paramagnetic probe, we were able to show the onset of cluster formation taking
      place with the addition of a fourth metal ion equivalent to the apo protein.
      Limited proteolytic digestion experiments complemented with mass spectrometry and
      amino acid analysis provide clear evidence for the presence of two separate metal
      thiolate clusters. One cluster consists of four metal ions and is made up by a
      part of the protein containing 11 cysteine residues, comparable to the situation
      found in the mammalian counterparts. The second cluster features two metal ions
      coordinated by six cysteine residues. The occurrence of the latter cluster is
      unprecedented in the metallothionein superfamily so far.

PMID- 17211633
TI  - Large germline deletions and duplication in isolated cerebral cavernous
      malformation patients.
AB  - Cerebral cavernous malformations (CCM) are vascular lesions that predispose to
      headaches, seizures, and hemorrhagic stroke. Hereditary CCMs are usually
      associated with the occurrence of multiple CCMs and occur with a frequency of
      1:2,000 to 1:10,000. In this study, eight isolated cases with multiple CCMs but
      no CCM1-3 point mutation were analyzed using the multiplex ligation-dependent
      probe amplification assay. Four genomic rearrangements were identified including
      a previously unreported large duplication within the CCM1 gene and a novel
      deletion involving the entire coding region of the CCM2 gene. Consequently,
      systematic screening for CCM deletions/duplications is recommended.

PMID- 17211634
TI  - Cloning and characterization of a maltotriose-producing alpha-amylase gene from
      Thermobifida fusca.
AB  - The gene (tfa), encoding a maltotriose-producing alpha-amylase from Thermobifida
      fusca NTU22, was cloned, sequenced and expressed in Escherichia coli. The gene
      consists of 1,815 base pairs and encodes a protein of 605 amino acids. The base
      composition of the tfa coding sequence is 69% G+C and the protein has a predicted
      pI value of 5.5. The deduced amino acid sequence of the tfa amylase exhibited a
      high degree of similarity with amylases from Thermomonospora curvata and
      Streptomyces amylases. The purified amylase could be detected as a single band of
      about 65 kDa by SDS-polyacrylamide gel electrophoresis and this agrees with the
      predicted size based on the nucleotide sequence. The optimal pH and temperature
      of the purified amylase were 7.0 and 60 degrees C, respectively. The properties
      of purified amylase from the E. coli transformant are similar to that of an
      amylase purified from the original T. fusca NTU22.

PMID- 17211632
TI  - The medial and lateral substantia nigra in Parkinson's disease: mRNA profiles
      associated with higher brain tissue vulnerability.
AB  - Sporadic Parkinson's disease (PD) is characterized by progressive death of
      dopaminergic neurons within the substantia nigra. However, pathological cell
      death within this nucleus is not uniform. In PD, the lateral tier of the
      substantia nigra (SNl) degenerates earlier and more severely than the more medial
      nigral component (SNm). The cause of this brain regional vulnerability remains
      unknown. We have used DNA oligonucleotide microarrays to compare gene expression
      profiles from the SNl to those of the SNm in both PD and control cases. Genes
      expressed more highly in the PD SNl included the cell death gene, p53 effector
      related to PMP22, the tumour necrosis factor (TNF) receptor gene, TNF receptor
      superfamily, member 21, and the mitochondrial complex I gene, NADH dehydrogenase
      (ubiquinone) 1beta subcomplex, 3, 12 kDa (NDUFbeta3). Genes that were more highly
      expressed in PD SNm included the dopamine cell signalling gene, cyclic adenosine
      monophosphate-regulated phosphoprotein, 21 kDa, the activated macrophage gene,
      stabilin 1, and two glutathione peroxidase (GPX) genes, GPX1 and GPX3. Thus,
      there is increased expression of genes encoding pro-inflammatory cytokines and
      subunits of the mitochondrial electron transport chain, and there is a decreased
      expression of several glutathione-related genes in the SNl suggesting a molecular
      basis for pathoclisis. Importantly, some of the genes that are differentially
      regulated in the SNl are known to be expressed highly or predominantely in glial
      cells. These findings support the view that glial cells can be primarily affected
      in PD emphasizing the importance of using a whole tissue approach when
      investigating degenerative CNS disease.

PMID- 17211636
TI  - Substrate inhibition kinetics of Saccharomyces cerevisiae in fed-batch cultures
      operated at constant glucose and maltose concentration levels.
AB  - Fed-batch culture is the mode of operation of choice in industrial baker's yeast
      fermentation. The particular mode of culture, operated at stable glucose and
      maltose concentration levels, was employed in this work in order to estimate
      important kinetic parameters in a process mostly described in the literature as
      batch or continuous culture. This way, the effects of a continuously falling
      sugar level during a batch process were avoided and therefore the effects of
      various (stable) sugar levels on growth kinetics were evaluated. Comparing the
      kinetics of growth and the inhibition by the substrate in cultures grown on
      glucose, which is the preferential sugar source for Saccharomyces cerevisiae, and
      maltose, the most common sugar source in industrial media for baker's yeast
      production, a milder inhibition effect by the substrate in maltose-grown cells
      was observed, as well as a higher yield coefficient. The observed sugar
      inhibition effect in glucostat cultures was taken into account in modeling
      substrate inhibition kinetics. The inhibition coefficient Ki increased with
      increasing sugar concentration levels, but it appeared to be unaffected by the
      type of substrate and almost equal for both substrates at elevated concentration
      levels.

PMID- 17211635
TI  - Purification, characterization, and crystallization of the components of a
      biphenyl dioxygenase system from Sphingobium yanoikuyae B1.
AB  - Sphingobium yanoikuyae B1 initiates the catabolism of biphenyl by adding dioxygen
      to the aromatic nucleus to form (+)-cis-(2R, 3S)-dihydroxy-1-phenylcyclohexa-4,6
      diene. The present study focuses on the biphenyl 2,3-dioxygenase system, which
      catalyzes the dioxygenation reaction. This enzyme has been shown to have a broad
      substrate range, catalyzing the dioxygenation of not only biphenyl, but also
      three- and four-ring polycyclic aromatic hydrocarbons. Extracts prepared from
      biphenyl-grown B1 cells contained three protein components that were required for
      the oxidation of biphenyl. The genes encoding the three components (bphA4, bphA3
      and bphA1f,A2f) were expressed in Escherichia coli. Biotransformations of
      biphenyl, naphthalene, phenanthrene, and benzo[a]pyrene as substrates using the
      recombinant E. coli strain resulted in the formation of the expected cis
      dihydrodiol products previously shown to be produced by biphenyl-induced strain
      B1. The three protein components were purified to apparent homogeneity and
      characterized in detail. The reductase component (bphA4), designated
      reductase(BPH-B1), was a 43 kD monomer containing one mol FAD/mol reductase(BPH
      B1). The ferredoxin component (bphA3), designated ferredoxin(BPH-B1), was a 12 kD
      monomer containing approximately 2 g-atoms each of iron and acid-labile sulfur.
      The oxygenase component (bphA1f,A2f), designated oxygenase(BPH-B1), was a 217 kD
      heterotrimer consisting of alpha and beta subunits (approximately 51 and 21 kD,
      respectively). The iron and acid-labile sulfur contents of oxygenase(BPH-B1) per
      alphabeta were 2.4 and 1.8 g-atom per mol, respectively. Reduced ferredoxin(BPH
      B1) and oxygenase(BPH-B1) each gave EPR signals typical of Rieske [2Fe-2S]
      proteins. Crystals of reductase(BPH-B1), ferredoxin(BPH-B1) and oxygenase(BPH-B1
      )diffracted to 2.5 A, 2.0 A and 1.75 A, respectively. The structures of the three
      proteins are currently being determined.

PMID- 17211637
TI  - Evidence of positive selection on the Atlantic salmon CD3gammadelta gene.
AB  - Atlantic salmon are typically anadromous, spending the majority of their lifetime
      in oceans and returning to fresh water to breed. This diversity of environments
      likely results in strong selective forces shaping their genome. In this paper, we
      present the first genomics approach to detect positive selection operating on the
      Salmo salar (salmon) lineage, an important aquaculture species. We identify a
      panel of candidate genes that may have been subject to adaptive evolution in this
      species. In particular, we identify a robust signature of positive selection
      operating on the salmon CD3gammadelta gene, which encodes one of the protein
      chains essential for formation of the T-cell receptor complex and for T-cell
      activation. Furthermore, we identified the particular codon sites that have been
      subject to positive selection in fish and highlight two sites flanking an
      important N-glycosylation site in this molecule.

PMID- 17211639
TI  - Mutations in autism susceptibility candidate 2 (AUTS2) in patients with mental
      retardation.
AB  - We report on three unrelated mentally disabled patients, each carrying a de novo
      balanced translocation that truncates the autism susceptibility candidate 2
      (AUTS2) gene at 7q11.2. One of our patients shows relatively mild mental
      retardation; the other two display more profound disorders. One patient is also
      physically disabled, exhibiting urogenital and limb malformations in addition to
      severe mental retardation. The function of AUTS2 is presently unknown, but it has
      been shown to be disrupted in monozygotic twins with autism and mental
      retardation, both carrying a translocation t(7;20)(q11.2;p11.2) (de la Barra et
      al. in Rev Chil Pediatr 57:549-554, 1986; Sultana et al. in Genomics 80:129-134,
      2002). Given the overlap of this autism/mental retardation (MR) phenotype and the
      MR-associated disorders in our patients, together with the fact that mapping of
      the additional autosomal breakpoints involved did not disclose obvious candidate
      disease genes, we ascertain with this study that AUTS2 mutations are clearly
      linked to autosomal dominant mental retardation.

PMID- 17211640
TI  - Harvest prediction in 'Algerie' loquat.
AB  - Plant phenology is in great measure driven by air temperature. To forecast
      harvest time for 'Algerie' loquat accurately, the growing degree days (GDD)
      needed from bloom to ripening were determined using data from nine seasons. The
      methods proposed by Zalom et al. (Zalom FG, Goodell PB, Wilson LT, Barnett WW,
      Bentley W, Degree-days: the calculation and use of heat units in pest management,
      leaflet no 21373, Division Agriculture and Natural Resources, University of
      California 10 pp, 1983) were compared as regards their ability to estimate heat
      summation based on hourly records. All the methods gave remarkably similar
      results for our cultivation area, although the double-sine method showed higher
      performance when temperatures were low. A base temperature of 3 degrees C is
      proposed for 'Algerie' loquat because it provides a coefficient of variation in
      GDD among seasons of below 5%, and because of its compatibility with loquat
      growth. Based on these determinations, 'Algerie' loquat requires 1,715 GDD from
      bloom to harvest; under our conditions this heat is accumulated over an average
      of 159 days. Our procedure permits the 'Algerie' harvest date to be estimated
      with a mean error of 4.4 days (<3% for the bloom-harvest period). GDD summation
      did not prove superior to the use of the number of calendar days for predicting
      'Algerie' harvest under non-limiting growing conditions. However, GDD reflects
      the developmental rate in water-stressed trees better than calendar days. Trees
      under deficit irrigation during flower development required more time and more
      heat to ripen their fruits.

PMID- 17211641
TI  - Microclimate of tree cavities during winter nights-implications for roost site
      selection in birds.
AB  - We examined the relationships between cavity temperature, ambient temperature
      outside the cavity and structural characteristics of 70 cavities measured for 1
      night to determine if cavity roosting birds may potentially select warmer tree
      cavities for wintertime roosting. The mean temperature increment of the cavity
      (=cavity-ambient temperature) varied from -2.4 to 4.9 degrees C and increased
      with higher day-to-night fluctuations in the ambient temperature, smaller cavity
      entrance and better health status of the cavity tree. Cavities in healthy trees
      were warmer than those in dead trees, but this difference disappeared with rising
      mean ambient temperatures. This interaction between the effects of tree health
      status and mean ambient temperature, as well as the effect of day-to-night
      fluctuations in the ambient temperature, were supported by the analysis of
      repeated measurements of temperature taken on 12 consecutive nights in five
      cavities. The variability in cavity microclimates makes the selection of warmer
      roost sites possible, and the predictors of microclimate may provide indirect
      cues to prospecting birds.

PMID- 17211638
TI  - Polymorphism in intron 1 of the interferon-gamma gene influences both serum
      immunoglobulin E levels and the risk for chronic hepatitis B virus infection in
      Polynesians.
AB  - Intron 1 of the interferon-gamma (IFNG) gene contains two polymorphisms. The 12
      CA-repeat allele of the +875 IFNGCA microsatellite and the T allele of the +A874T
      single nucleotide polymorphism (SNP) have been associated with increased in vitro
      IFNG production and a variety of clinical phenotypes. The purpose of this study
      was to determine whether these polymorphisms influence total serum IgE levels
      [tsIgE] and the outcome of a hepatitis B virus (HBV) infection. IFNGCA and +A874T
      were typed in 186 asthmatics of Niuean ancestry and in Polynesian women with a
      chronic HBV infection (n = 60) and with natural immunity to the HBV (n = 66). The
      IFNGCA genotype was associated with [tsIgE] in asthmatic children (n = 51, p =
      0.004) but not adults (n = 135, p = 0.87). The data were consistent with a co
      dominant influence of the 12 CA-repeat allele on high [tsIgE]. The IFNGCA
      genotype was also associated with the risk for chronic HBV infection (chi (2) =
      11.6, p = 0.003) because of a dominant effect of the 12 CA-repeat allele on
      developing natural immunity in homozygotes (OR = 5.8, p = 0.003) and
      heterozygotes (OR = 2.7, p = 0.01). Similar associations were found for the T
      allele of the +A874T SNP. The possibility that these associations were due to
      linked alleles in the adjacent 783 bp of the promoter and 3'-untranslated region
      of the IFNG gene was excluded by direct sequencing. In summary, high-IFNG
      producing alleles in intron 1 of the IFNG locus are associated with high [tsIgE]
      in asthmatic children from Niue and with natural immunity to the HBV in
      Polynesian women. These findings are consistent with a previous report of an
      association between +875 IFNGCA and [tsIgE] and provide preliminary evidence of a
      new association with the outcome of an HBV infection.

PMID- 17211643
TI  - [Palliative medicine--state of the art].

PMID- 17211642
TI  - [Palliative sedation].
AB  - Terminal illnesses can cause distressing symptoms such as severe pain, mental
      confusions, feelings of suffocation, and agitation. Despite skilled palliative
      care in some cases these symptoms may not respond to standard interventions.
      After all other means to provide comfort and relief to a dying patient have been
      tried and are unsuccessful, clinical caregivers and patients can consider
      palliative sedation. Sedation in the context of palliative medicine is the
      monitored use of medications to induce varying degrees of unconsciousness to
      bring about a state of decreased or absent awareness in order to relieve the
      burden of otherwise refractory suffering. Palliative sedation is not intended to
      cause death or shorten life. The patient and family should agree with plans for
      palliative sedation. Because cases involving palliative sedation are emotionally
      stressful, the patient, family, and health care workers can all benefit from
      talking about the complex medical, ethical, and emotional issues they raise.

PMID- 17211645
TI  - [17th Annual Congress of the Kidney Transplantation Professional Circle of the
      German Society of Urology].

PMID- 17211644
TI  - [Palliative and supportive treatment options in patients with advanced prostate
      cancer].
AB  - In patients with advanced prostate cancer, quality of life and prevention of
      complications come to the fore. Besides handling local complications such as
      obstruction, hematuria and lymphedema, treatment of bone metastases and their
      complications is of great importance. Analgesic measures, bisphosphonates,
      radiation therapy, radionuclide therapy and neurosurgical procedures are
      available. Spinal cord compression with acute motor and sensory deficiency
      requires immediate neurosurgical and/or radiation therapy. Tumor anemia should be
      treated appropriately.

PMID- 17211646
TI  - Hypobaric hypoxia reduces the amplitude of oscillatory potentials in the human
      ERG.
AB  - PURPOSE: To explore the retinal functions in healthy volunteers during acute
      hypoxic exposure, applying a set of electrophysiological tests. METHODS: Standard
      electroretinograms (ERGs) of the retina (rod-(scotopic) ERGs, cone-(photopic)
      ERGs, maximal responses and oscillatory potentials (OPs)) and 30-Hz flicker ERGs
      were recorded according to ISCEV (International Society of Clinical
      Electrophysiology of Vision) recommendations in 14 healthy volunteers during a 15
      min exposure to a simulated altitude of 5500 m. RESULTS: The mean arterial oxygen
      saturation level was significantly reduced (P < 0.001) during the hypobaric
      challenge. It returned to the normal level very shortly after the end of the
      hypoxic exposure. No significant change in the latency or amplitude of the slow
      components of the ERG was found in any recording. The OPs of the ERG, however,
      revealed a significant decrease in amplitude during hypoxic exposure. Both OP1
      and OP2 amplitudes were significantly different (P < 0.05) from the baseline
      values during hypoxia. Partial recovery of these waves occurred after termination
      of the hypoxia. CONCLUSIONS: These results appear to support the notion that the
      inner layers of the retina presumed to be the main source of the OPs, display the
      highest sensitivity towards circulatory and/or hypoxic challenges.

PMID- 17211648
TI  - The effects of a single session of inescapable tailshock on the subsequent
      locomotor response to brief footshock and cocaine administration in rats.
AB  - RATIONALE: We have previously shown that exposure to a single session of
      inescapable (IS), but not escapable (ES), tailshock can sensitize the subsequent
      conditioned place preference and locomotor responses to opioids, but not other
      drug classes. However, prior work suggests that IS might sensitize nonopioid drug
      responding if the drug were to be preceded by a mild stressor. OBJECTIVES: In the
      following experiments, we examined the effects of IS and ES on the subsequent
      locomotor response to brief footshock and/or cocaine administration. METHODS:
      First, we measured the locomotor response to cocaine (0, 1, 5, 10 mg/kg,
      intraperitoneally) 48 h after a single session of IS in adult, male Sprague
      Dawley rats. Then, this procedure was repeated with 10 mg/kg cocaine, except that
      half of the rats received two footshocks immediately before drug administration.
      Finally, we manipulated the escapability of the initial stressor, as rats
      received either ES or yoked IS 48 h prior to footshock and cocaine
      administration. RESULTS: IS did not affect the subsequent locomotor response to
      cocaine, but did enhance this response when cocaine administration was
      immediately preceded by two footshocks. The footshocks alone were without effect.
      This sensitizing effect was dependent on the escapability of the initial
      stressor, as ES did not alter the locomotor response to footshock and cocaine
      administration. CONCLUSIONS: These results indicate that acute exposure to IS,
      but not ES, can sensitize the locomotor response to cocaine 48 h later, but only
      when cocaine administration is immediately preceded by a brief stressor.

PMID- 17211647
TI  - The effects of a single exposure to uncontrollable stress on the subsequent
      conditioned place preference responses to oxycodone, cocaine, and ethanol in
      rats.
AB  - RATIONALE: Acute stress has been shown to facilitate the rewarding effects of a
      number of commonly abused drugs, although the stressor typically must be
      administered either immediately before or during drug administration and often in
      the same environment. We have previously reported that a single session of an
      uncontrollable (inescapable tailshock, IS), but not controllable (escapable
      tailshock, ES), stressor can enhance the conditioned place preference (CPP)
      response to morphine, even when stressor and drug administration are separated
      temporally and spatially. However, this persistent, trans-situational enhancement
      did not occur to amphetamine CPP. OBJECTIVES: The following experiments were
      conducted to determine whether the long-term effects of IS on drug reward are
      specific to opioids. MATERIALS AND METHODS: Adult, male Sprague-Dawley rats were
      exposed to a single session of IS or remained in their home cages (HC). Twenty
      four hours later, using an unbiased procedure, CPP conditioning was conducted
      with either oxycodone (0, 2, or 5 mg/kg, sc), cocaine (0, 1, 5, or 10 mg/kg, ip),
      or ethanol (0.3, 1, or 2 g/kg, ip). Another group of rats were exposed to IS, ES,
      or HC treatment and conditioned with oxycodone (5 mg/kg, sc) 24 h later. RESULTS:
      IS enhanced the subsequent CPP response to oxycodone, but not cocaine or ethanol.
      This enhancement was dependent on the controllability of the stressor, as ES did
      not affect oxycodone CPP. CONCLUSIONS: These results indicate that the long-term,
      trans-situational enhancing effect of uncontrollable stress on drug reward is
      specific to opioids.

PMID- 17211649
TI  - Differential anxiogenic, aversive, and locomotor effects of THC in adolescent and
      adult rats.
AB  - RATIONALE: Unpleasant side effects of drugs of abuse often limit their repeated
      use; however, such effects may be attenuated in adolescents compared to adults.
      OBJECTIVES: We investigated whether the anxiogenic, aversive, or locomotor
      effects of delta-9-tetrahydrocannabinol (THC) differ between adolescent and adult
      rats. METHODS: We used the elevated plus maze (EPM) and light-dark tests of
      anxiety, the conditioned taste aversion and conditioned place aversion (CPA)
      tests of generalized aversion, and measures of stress hormone levels in serum to
      examine effects of THC in adolescent and adult rats. Locomotor activity was also
      recorded in the EPM, light-dark task, and CPA association sessions. RESULTS: In
      the EPM and light-dark tasks, THC was anxiogenic in both age groups, but the drug
      was more anxiogenic in adults than in adolescents. In the place and taste
      aversion tasks, THC was aversive in both ages, and at 1.25 and 5 mg/kg, was more
      aversive in adults than in adolescents. The locomotor response to THC, as
      measured in the anxiety tasks and CPA, affected adults more than adolescents.
      Multiple measures revealed a locomotor-decreasing effect in adults, whereas some
      measures suggested a small locomotor-increasing effect in adolescent rats.
      CONCLUSIONS: These results suggest that THC can have greater anxiogenic,
      aversive, and locomotor-reducing effects in adult rats than in adolescent rats.
      These findings suggest an explanation for reduced marijuana use in adult humans
      compared to teenagers.

PMID- 17211650
TI  - Conditioned effects of heroin on the expression of inducible nitric oxide
      synthase in the rat are susceptible to extinction and latent inhibition.
AB  - RATIONALE: The administration of heroin has been shown to inhibit the induction
      of nitric oxide, a molecule known to play a critical role in immune function.
      Previous research has shown that this alteration can be conditioned to
      environmental stimuli that have been associated with drug administration.
      However, it remains unknown whether the conditioned effects of heroin on nitric
      oxide formation follow accepted principles of learning. OBJECTIVE: This study
      sought to determine whether manipulations that induce extinction and latent
      inhibition, two learning paradigms known to reduce the expression of conditioned
      responses, would alter heroin's conditioned effects on the expression of
      inducible nitric oxide synthase (iNOS). MATERIALS AND METHODS: The conditioning
      procedure involved repeated pairing of heroin administration with placement into
      a standard conditioning chamber. Rats were repeatedly exposed to the chambers
      without heroin reinforcement to determine whether the conditioned response would
      extinguish. To induce latent inhibition, rats received repeated exposure to the
      chamber before the start of conditioning to inhibit the acquisition of the
      conditioned response. Ten days after the final conditioning session, all rats
      were injected with lipopolysaccharide (LPS) to induce iNOS expression. Spleen and
      liver tissue were removed to determine iNOS expression using reverse
      transcriptase polymerase chain reaction. Blood was collected to determine the
      concentration of nitrite/nitrate. RESULTS: The results showed that both
      extinction and latent inhibition reduced the conditioned effects of heroin on the
      production of nitric oxide. CONCLUSION: This study provides the first evidence
      that the conditioned effects of heroin on nitric oxide production follow accepted
      principles of learning.

PMID- 17211651
TI  - Behavioral effects of morphine and cocaine in M1 muscarinic acetylcholine
      receptor-deficient mice.
AB  - RATIONALE: Muscarinic acetylcholine receptors (M1-M5) modulate the activity of
      the central nervous system and an array of physiological functions. Recent
      evidence has also implicated muscarinic receptors in behavioral effects of drugs
      of abuse such as morphine and cocaine. However, the genetic similarity between
      muscarinic receptors and the coexpression of multiple subtypes in most cells has
      impeded the development of selective antagonists and the determination of the
      role of each muscarinic receptor subtype in morphine's and cocaine's behavioral
      effects. OBJECTIVE: The present studies employ mice deficient in the M1 receptor
      subtype (M1 KO) to assess morphine antinociception (2.5, 5.0, 10, or 20 mg/kg)
      and the conditioned rewarding effects of morphine and cocaine (2.5, 5.0, or 10
      mg/kg). METHODS: M1 KO and their wild-type (WT) littermates were tested using a
      56 degrees C hotplate assay and a conditioned place preference procedure.
      Parallel studies using the M1 receptor antagonist, pirenzepine, were also
      conducted in the background strain C57BL6 mice. RESULTS: The results demonstrate
      that M1 KO mice display a greater antinociceptive effect of morphine in the
      hotplate assay; however, the effects of morphine as well as cocaine were
      attenuated in the conditioned place preference procedure. Comparable results were
      obtained with the pharmacological antagonism of the M1 receptor by pirenzepine.
      CONCLUSIONS: These results suggest a modulatory role of the M1 muscarinic
      receptor in opioid antinociception and conditioned drug reward, and demonstrate
      the utility of M1 receptor knockout models for the determination of the role of
      the M1 subtype in the behavioral effects of morphine and cocaine.

PMID- 17211652
TI  - The effects of buprenorphine on fentanyl withdrawal in rats.
AB  - RATIONALE: Fentanyl is a potent mu-opioid receptor agonist that is widely used
      for the treatment of severe chronic pain. Discontinuation of fentanyl
      administration has been shown to induce a negative emotional state. OBJECTIVES:
      The aim of the present studies was to investigate the effects of the partial mu
      opioid receptor agonist buprenorphine on the negative emotional state associated
      with precipitated and spontaneous fentanyl withdrawal in rats. MATERIALS AND
      METHODS: Fentanyl and saline were chronically administered via osmotic minipumps.
      A discrete-trial intracranial self-stimulation procedure was used to provide a
      measure of brain reward function. Somatic signs were recorded from a checklist of
      opioid abstinence signs. RESULTS: Naloxone induced a deficit in brain reward
      function in rats chronically treated with fentanyl. Buprenorphine dose
      dependently prevented the naloxone-induced deficit in brain reward function.
      Discontinuation of fentanyl administration was also associated with a deficit in
      brain reward function. After explantation of the minipumps, the administration of
      buprenorphine induced a potentiation of brain reward function in the fentanyl
      withdrawing rats, but did not affect brain reward function of saline-treated
      control rats. Buprenorphine prevented the somatic withdrawal signs associated
      with spontaneous fentanyl withdrawal and attenuated the somatic signs associated
      with precipitated fentanyl withdrawal. CONCLUSIONS: Buprenorphine prevents
      affective and somatic fentanyl withdrawal signs. Moreover, buprenorphine is
      rewarding in rats previously exposed to fentanyl, but not in opioid-naive rats.
      This pattern of results suggests that buprenorphine may be an effective treatment
      for the anhedonic-state associated with fentanyl withdrawal, but further study of
      buprenorphine's abuse potential is warranted.

PMID- 17211653
TI  - The disruptive effects of the CB1 receptor antagonist rimonabant on extinction
      learning in mice are task-specific.
AB  - RATIONALE: Disruption of CB(1) receptor signaling through the use of CB(1) (-/-)
      mice or the CB(1) receptor antagonist rimonabant (SR141716) has been demonstrated
      to impair extinction of learned responses in conditioned fear and Morris water
      maze tasks. In contrast, CB(1) (-/-) mice exhibited normal extinction rates in an
      appetitively motivated operant conditioning task. OBJECTIVES: The purpose of this
      study was to test whether rimonabant would differentially disrupt extinction
      learning between fear-motivated and food-motivated tasks. MATERIALS AND METHODS:
      Separate groups of C57BL/6J mice were trained in two aversively motivated tasks,
      conditioned freezing and passive avoidance, and an appetitively motivated operant
      conditioning task at a fixed ratio (FR-5) schedule of food reinforcement. After
      acquisition, the respective reinforcers in each task were withheld, and an
      intraperitoneal injection of vehicle or rimonabant was given 30 min before each
      extinction session. RESULTS: Rimonabant (3 mg/kg) treatment significantly
      disrupted extinction in both the conditioned freezing and passive avoidance tasks
      but failed to affect extinction rates in the operant conditioning task, whether
      using daily or weekly extinction sessions. Interestingly, rimonabant (3 mg/kg)
      prevented the significant increases in lever pressing (i.e., extinction burst)
      that occurred during the first extinction session of the operant conditioning
      task. CONCLUSIONS: These results support the hypothesis that the CB(1) receptor
      plays a vital role in the extinction of aversive memories but is not essential
      for extinction of learned responses in appetitively motivated tasks.

PMID- 17211654
TI  - Video game epilepsy in the twentieth century: a review.
AB  - INTRODUCTION: Visually evoked seizures have been reported for almost 2,000 years.
      This source of seizure activity, however, seems to have increased recently with
      the advent of new technologies used for television and computer games. METHODS:
      The present paper reviews the literature regarding this interesting phenomenon.
      RESULTS: After our review, it does appear that visually evoked seizures have
      increased in frequency during the twentieth century. CONCLUSIONS: We believe that
      knowledge of visually evoked seizures may aid neuroscientists in further
      exploration of the pathophysiology of seizure activity and its related preventive
      measures. Further studies are necessary to prove the etiology of such seizure
      activity.

PMID- 17211655
TI  - Paraneoplastic syndromes of hypercalcemia and leukocytosis associated with
      colonic metastases from squamous cell carcinoma of the lung.

PMID- 17211656
TI  - Activity concentrations of 226Ra, 228Th, and 40K in different food crops from a
      high background radiation area in Bitsichi, Jos Plateau, Nigeria.
AB  - One of the three goals of the United Nations for sustainable food security is to
      ensure that all people have access to sufficient, nutritionally adequate, and
      safe food. Decades of tin mining in the Bitsichi area of the Jos Plateau,
      Nigeria, have left a legacy of polluted water supplies, impoverished agricultural
      land, and soil containing abnormally high levels of naturally occurring
      radioactive elements. In order to ascertain the radiological food safety of the
      population, different crops that constitute the major food nutritive requirements
      were collected directly across farmlands in the area. The activity concentrations
      of (226)Ra, (228)Th, and (40)K were determined in the food and soil samples using
      gamma-ray spectrometry. Additionally, in situ gamma dose rate measurements were
      performed on the farms using a pre-calibrated survey meter. The corresponding
      activity concentrations in the food crops ranged from below detection limit (BDL)
      to 684.5 Bq kg(-1) for (40)K, from BDL to 83.5 Bq kg(-1) for (226)Ra, and from
      BDL to 89.8 Bq kg(-1) for (228)Th. Activity concentrations of these radionuclides
      were found to be lower in cereals than in tubers and vegetables. As for the soil
      samples, activity concentrations of these radionuclides varied from BDL to 166.4
      Bq kg(-1), from 10.9 to 470.6 Bq kg(-1), and from 122.7 to 2,189.5 Bq kg(-1) for
      (40)K, (226)Ra, and (228)Th, respectively. Average external gamma dose rates were
      found to vary across the farms from 0.50 +/- 0.01 to 1.47 +/- 0.04 microSv h(-1).
      Due to past mining activities, the soil radioactivity in the area has been
      modified and the concentration level of the investigated natural radionuclides in
      the food crops has also been enhanced. However, the values obtained suggest that
      the dose from intake of these radionuclides by the food crops is low and that
      harmful health effects are not expected.

PMID- 17211657
TI  - Technical developments at the NASA Space Radiation Laboratory.
AB  - The NASA Space Radiation Laboratory (NSRL) located at Brookhaven National
      Laboratory (BNL) is a center for space radiation research in both the life and
      physical sciences. BNL is a multidisciplinary research facility operated for the
      Office of Science of the US Department of Energy (DOE). The BNL scientific
      research portfolio supports a large and diverse science and technology program
      including research in nuclear and high-energy physics, material science,
      chemistry, biology, medial science, and nuclear safeguards and security. NSRL, in
      operation since July 2003, is an accelerator-based facility which provides
      particle beams for radiobiology and physics studies (Lowenstein in Phys Med
      17(supplement 1):26-29 2001). The program focus is to measure the risks and to
      ameliorate the effects of radiation encountered in space, both in low earth orbit
      and extended missions beyond the earth. The particle beams are produced by the
      Booster synchrotron, an accelerator that makes up part of the injector sequence
      of the DOE nuclear physics program's Relativistic Heavy Ion Collider. Ion species
      from protons to gold are presently available, at energies ranging from <100 to
      >1,000 MeV/n. The NSRL facility has recently brought into operation the ability
      to rapidly switch species and beam energy to supply a varied spectrum onto a
      given specimen. A summary of past operation performance, plans for future
      operations and recent and planned hardware upgrades will be described.

PMID- 17211658
TI  - Antiplasmodial activity of novel stilbene derivatives isolated from
      Parthenocissus tricuspidata from South Korea.
AB  - New stilbene glycoside, piceid-(1-->6)-beta-D -glucopyranoside (compound 2, Fig.
      1), was isolated from the MeOH extract of the leaves of Parthenocissus
      tricuspidata (Vitaceae) together with four known compounds, piceid (compound 1,
      Fig. 1), resveratrol (compound 3, Fig. 1), longistylin A (compound 4, Fig. 1),
      and longistylin C (compound 5, Fig. 1). Their structures were determined
      spectroscopically, particularly by 2D nuclear magnetic resonance (NMR)
      spectroscopic and chemical analysis. The antiplasmodial activity of isolated
      compounds were determined in vitro against a chloroquine-sensitive strain of
      Plasmodium falciparum (D10). Among the compounds isolated, piceid-(1-->6)-beta-D
      glucopyranoside (2) had the most potential inhibition, with inhibitory
      concentration (IC(50)) values of 5.3 microM. To our knowledge, antiplasmodial
      activity of functional group position of stilbene is now being reported for the
      first time in this study. The result shows that the 3, 4'-position in stilbenes
      might play an essential role in antiplasmodial activity.

PMID- 17211659
TI  - Anthelmintic activity of Spigelia anthelmia extract against gastrointestinal
      nematodes of sheep.
AB  - In vitro (larval development assay) and in vivo studies were conducted to
      determine possible direct anthelmintic effect of ethanolic and aqueous extracts
      of Spigelia anthelmia towards different ovine gastrointestinal nematodes. The
      effect of extracts on development and survival of infective larvae stage (L(3))
      was assessed. Best-fit LC(50) values were computed by global model of non-linear
      regression curve fitting (95% confidence interval). Therapeutic efficacy of the
      ethanolic extracts administered orally at a dose rate of 125, 250, and 500 mg/kg,
      relative to a non-medicated control group of sheep harbouring naturally acquired
      infection of gastrointestinal nematodes, was evaluated in vivo.The presence of S.
      anthelmia extracts in the cultures decreased the survival of L(3) larvae. The
      LC(50) of aqueous extract (0.714 mg/ml) differ significantly from the LC(50) of
      the ethanolic extract (0.628 mg/ml) against the strongyles (p < 0.05, paired t
      test). Faecal egg counts on day 12 after treatment showed that the extract is
      effective, relative to control (one-way analysis of variance [ANOVA], Dunnett's
      multiple comparison test) at 500 mg/kg against Strongyloides spp. (p < 0.01), 250
      mg/kg against Oesophagostomum spp., Trichuris spp. (p < 0.05), and 125 mg/kg
      against Haemonchus spp. and Trichostrongylus spp. (p < 0.01). The effect of the
      doses is significant in all cases, the day after treatment is also extremely
      significant in most cases, whereas interaction between dose and day after
      treatment is significant (two-way ANOVA). S. anthelmia extract could, therefore,
      find application in the control of helminth in livestock, by the ethnoveterinary
      medicine approach.

PMID- 17211660
TI  - Morphological differentiation among three Thelazia species (Nematoda:
      Thelaziidae) by scanning electron microscopy.
AB  - Thelaziasis is an ocular infection of several mammals caused by nematodes of the
      genus Thelazia (Spirurida, Thelaziidae). The adults live in the lachrymal ducts
      and conjunctival sacs of infected animals, and transmission occurs by means of
      different species of muscids. T. rhodesi, T. skrjabini, and T. gulosa affect
      mainly cattle, inducing conjunctivitis, keratitis, and ocular discharge. This
      article describes the morphological features of adult T. rhodesi, T. skrjabini,
      and T. gulosa by scanning electron microscopy and highlights the most relevant
      differences for their identification.

PMID- 17211661
TI  - Casas Muertas and Oficina No. 1: internal migrations and malaria trends in
      Venezuela 1905-1945.
AB  - To compare internal migration and temperature as factors behind the decreasing
      trend in malaria deaths observed in Venezuela from 1905 to 1945, linear
      autoregressive models are fitted to a historical dataset. The model that only
      incorporates internal migration is the one with the best fit. The decreasing
      trend in malaria deaths in Venezuela, from 1905 to 1945, is not explained by a
      trend in mean annual temperature, but it is associated with an increase in the
      proportion of population in the Capital District, during a time period when the
      area was the principal attractor of migrations within the country.

PMID- 17211662
TI  - Giardia and Cryptosporidium in water buffaloes (Bubalus bubalis).
AB  - A cross-sectional survey of Giardia duodenalis and Cryptosporidium parvum
      infection in the water buffalo (Bubalus bubalis) was carried out in central
      Italy. A geographical information system (GIS) was constructed utilizing as data
      layers the topographic base map and the digital aerial photographs of the study
      area, as well as the geo-referenced points of all the buffalo farms. The survey
      was conducted on a sample of 90 farms, selected using a grid approach followed by
      proportional allocation. For this purpose, a grid representing quadrants of 5 x 5
      km was overlaid on the study area within the GIS. As a result, the study area was
      divided in equal quadrants, and the number of farms sampled in each quadrant was
      proportional to the total number of study population in that quadrant. On each
      farm, faecal samples were collected per rectum from three to five asymptomatic
      buffalo calves, aged from 1 to 9 weeks. The total number of faecal samples
      collected was 347. Each faecal sample was tested for the presence of copro
      antigens of G. duodenalis and of C. parvum using two commercially available
      enzyme-linked immunosorbent assays. Out of the 90 farms, 27 (30.0%) resulted
      positive for G. duodenalis and 22 (24.4%) for C. parvum. Co-infection was found
      in ten (11.1%) farms. With respect to animals, out of the 347 faecal samples, 63
      (18.1%) were found to have antigens of G. duodenalis and 51 (14.7%) of C. parvum.
      Co-infection was found in ten buffalo calves (2.9%). The results of the logistic
      regression models showed a positive association between the positivity to G.
      duodenalis and the presence of sheep on farm and between the positivity to C.
      parvum and the high number of buffaloes on farms. No significant co-infection
      between the two protozoa was found. In conclusion, the findings of the present
      study, derived from a systematic territorial survey planned with GIS, are
      noteworthy because they provided additional data on C. parvum and the first
      evidence of G. duodenalis infection in water buffaloes.

PMID- 17211664
TI  - Usefulness of magnetic resonance imaging in eosinophilic fasciitis.

PMID- 17211663
TI  - Motor imagery of gait: a quantitative approach.
AB  - Motor imagery (MI) is widely used to study cognitive aspects of the neural
      control of action. Prior studies were mostly centred on hand and arm movements.
      Recently a few studies have used imagery tasks to explore the neurophysiology of
      human gait, but it remains unclear how to ascertain whether subjects actually
      perform imagery of gait as requested. Here we describe a new experimental
      protocol to quantify imagery of gait, by behaviourally distinguishing it from
      visual imagery (VI) processes and by showing its temporal correspondence with
      actual gait. Fourteen young healthy subjects performed two imagery tasks and an
      actual walking (AW) task. During both imagery tasks subjects were sitting on a
      chair and faced a computer screen that presented photographs of walking
      trajectories. During one task (MI), subjects had to imagine walking along the
      walking trajectory. During the other task (VI), subjects had to imagine seeing a
      disc moving along the walking trajectory. During the AW task, subjects had to
      physically walk along the same walking trajectory as presented on the photographs
      during the imagery tasks. We manipulated movement distance by changing the length
      of the walking trajectory, and movement difficulty by changing the width of the
      walking trajectory. Subjects reported onset and offset of both actual and
      imagined movements with a button press. The time between the two button presses
      was taken as the imagined or actual movement time (MT). MT increased with
      increasing path length and decreasing path width in all three tasks. Crucially,
      the effect of path width on MT was significantly stronger during MI and AW than
      during VI. The results demonstrate a high temporal correspondence between
      imagined and AW, suggesting that MI taps into similar cerebral resources as those
      used during actual gait. These results open the possibility of using this
      protocol for exploring neurophysiological correlates of gait control in humans.

PMID- 17211665
TI  - Ultradian rhythms and the nutritional importance of caecotrophy in captive
      Brandt's voles (Lasiopodomys brandtii).
AB  - Ingestion of soft faeces derived from caecal contents, caecotrophy, in
      herbivorous small mammals is considered an adaptation to the metabolic
      disadvantage of small body size, especially when feeding on diets of low quality.
      We investigated daily activity patterns in captive Brandt's voles (Lasiopodomys
      brandtii), including feeding, locomotion, caecotrophy, and defaecation, by
      continuous 24 h visual observation; and estimated the contribution of soft faeces
      ingestion (caecotrophy) to intake of protein and energy. Brandt's voles ingested
      68.8 +/- 7.4 fecal pellets per day, averaging 17 +/- 2% of total faeces produced.
      The amount of faeces ingested did not differ between female and male voles or
      between night and day time. All animals showed average 3 h ultradian cycles in
      behaviour during the course of the day and night. The contributions of
      caecotrophy to the dietary intake of crude protein and metabolizable energy were
      estimated respectively as 9 and 8% on a high-protein, easily digested commercial
      rabbit pellet diet. However, the importance of caecotrophy to the field voles is
      likely to be higher on a natural diet of lower nutrient density. The rhythm of
      caecotrophy in voles depended mainly on the rhythm of the colonic separation
      mechanism in the proximal colon and passage in the distal colon, and may be
      regulated by feeding and other activity rhythms. Ultradian rhythms in caecotrophy
      helped to minimise potential conflicts in utilizing the gut, especially in
      balancing the caecal fermentation and salvaging nutrients contained in caecal
      bacteria.

PMID- 17211666
TI  - Nitric oxide decreases ammonium release in tadpoles of the clawed frog, Xenopus
      laevis, Daudin.
AB  - In the present study, we quantified the physiological consequences of nitric
      oxide (NO) on ammonium release in tadpoles of Xenopus laevis. Tadpoles exposed to
      S-nitro-N-acetylpenicillamine (SNAP), an NO-donor, or L: -arginine, the substrate
      of NO synthase (NOS), showed a reversible decrease, whereas animals exposed to
      the NOS inhibitor Nomega-methyl-L: -arginine (L: -NMMA) exhibited an increase in
      ammonium release. Release of ammonium may be of physiological relevance during
      stress response of the animal. Handling of tadpoles as well as exposure to
      hyposmotic environments increased ammonium release. To localize NO synthesizing
      cells, we used diaminofluorescein-diacetate (DAF-2DA), an NO-sensitive
      fluorescent dye, and NADPH-diaphorase histochemistry, an indicator for NOS
      activity. We observed a fluorescence signal as well as NADPH-diaphorase activity
      in small, solitary cells in the epidermis. Similarly to NADPH-diaphorase
      histochemistry, silver nitrate staining and rhodamine labelling, markers for
      mitochondria-rich cells, showed a strong reaction in these cells. These
      observations indicate that NO (1) inhibits ammonium release, and (2) is
      endogenously synthesized in mitochondria-rich cells in Xenopus tadpoles. Based on
      our histochemical results, we speculate that gill epithelium and epidermis work
      in parallel to release ammonium as epidermal tissue contains mitochondria-rich
      and NADPH-diaphorase positive cells.

PMID- 17211668
TI  - [Urogenital chlamydial infections in women and men].
AB  - Genital infections with Chlamydia trachomatis occur in all social groups in
      Germany. About 100,000 German women are sterile because of tubal scarring due to
      chlamydiae. Genital chlamydial infections are asymptomatic in 70% of patients,
      even if salpingitis occurs. Typical symptoms of chlamydial infection are purulent
      cervicitis with vaginal discharge, painful cervical bleeding because of
      endometritis, lower abdominal pain with dyspareunia, and upper abdominal pain
      because of perihepatitis. DNA amplification tests on first voided urine or
      cervical swab are the most sensitive routine tests. Specific serum antibodies to
      C. trachomatis indicate a previous infection in sterile women. For treatment, a
      10-14 day course of doxycycline 200 mg daily or a macrolide antibiotic in the
      patient as well as in the sexual partner is recommended. In the male, C.
      trachomatis causes urethritis and epididymitis. Opinions differ about involvement
      of the prostate gland and seminal vesicles. Identification of C. trachomatis
      antigen or DNA in the accessory gland secretions is not sufficiently
      reproducible. The two vectors are easily diagnosed in urethral swabs or in urine.
      The occurrence of chlamydial antibodies in serum or in seminal fluid is not a
      sign of current infection. Reliable studies which indicate a reduced fertility of
      men infected with C. trachomatis are not available.

PMID- 17211667
TI  - Gastrointestinal transport of Ca2+ and Mg2+ during the digestion of a single meal
      in the freshwater rainbow trout.
AB  - A diet containing an inert marker (ballotini beads, quantified by X-radiography)
      was used to quantify the transport of two essential minerals, Ca(2+) and Mg(2+)
      from the diet during the digestion and absorption of a single meal of commercial
      trout food (3% ration). Initially, net uptake of Ca(2+) was observed in the
      stomach followed by subsequent Ca(2+) fluxes along the intestine which were
      variable, but for the most part secretory. This indicated a net secretion of
      Ca(2+) along the intestinal tract resulting in a net assimilation of dietary
      Ca(2+) of 28%. Similar handling of Ca(2+) and Mg(2+) was observed along the
      gastrointestinal tract (GI), although net assimilation differed substantially
      between the cations, with Mg(2+) assimilation being close to 60%, mostly a result
      of greater uptake by the stomach. The stomach displayed the highest net uptake
      rates for both cations (1.5 and 1.3 mmol kg(-1) fish body mass for Ca(2+) and
      Mg(2+), respectively), occurring within 2 h following ingestion of the meal.
      Substantial secretions of both Ca(2+) and Mg(2+) were observed in the anterior
      intestine, which were attributed to bile and other intestinal secretions, while
      fluxes in the mid and posterior intestine were small and variable. The overall
      patterns of Ca(2+) and Mg(2+) handling in the GI tract were similar to those
      observed for Na(+) and K(+) (but not Cl(-)) in a previous study. Overall, these
      results emphasize the importance of dietary electrolytes in ionoregulatory
      homeostasis.

PMID- 17211669
TI  - [Extranodal marginal zone B-cell lymphoma of MALT-type].
AB  - Extranodal marginal zone B-cell lymphomas of the MALT type constitute, with
      around 8% of all B-cell lymphomas, the third most frequent lymphoma in the
      Western hemisphere. Their unifying characteristic principle is their origin in
      organs that are typically devoid of a regular lymphatic parenchyma ("primary"
      MALT). In contrast, "secondary" MALT is acquired in these sites by chronic
      inflammatory processes triggered by chronic infections or autoimmune diseases.
      The organotypic characteristics of these particular lymphoid tumours are also
      mirrored by organ-specific precursor lesions and in tumour biology. Usually, MALT
      type lymphomas remain confined to their site of origin for a long time,
      disseminating only late during the course of the disease. Hence, they may be
      controlled by local treatment (excision, irradiation). Moreover, the distinctive
      genetic constitution of MALT-type lymphomas, although varying from organ to
      organ, indicates particular transformation pathways obviously related to the
      specific precursor lesion and, hence, of organ-specific quality.

PMID- 17211670
TI  - [Enteropathy type T-cell lymphomas: pathology and pathogenesis].
AB  - Enteropathy type T-cell lymphomas (ETL) are the most frequent T-cell lymphomas
      arising in the gastrointestinal tract. Commonly, the neoplasm is clinically
      associated with symptoms of malabsorption, and it frequently manifests as a
      spontaneous bowel perforation. Among ETL, two types can be distinguished by
      morphology, immunophenotype and, possibly, by pathogenesis. A total of 80% of ETL
      are characterized by a close association with celiac disease, pleomorphic
      cytomorphology and the rare expression of CD8 and CD56. In contrast, 20% of ETL
      show a monomorphic small to medium size cytomorphology and frequent expression of
      CD8 and CD56, an association with celiac disease is rare in the latter cases.
      Genetically, ETL is characterized by frequent and recurrent chromosomal gains of
      9q33-q34.

PMID- 17211671
TI  - [Extranodal diffuse large B-cell lymphoma--an organotypic disease?].
AB  - Roughly 30-40% of diffuse large B-cell lymphomas (DLBCL) arise primarily in
      extranodal sites. Most frequently, they occur in the gastrointestinal tract,
      especially in the gastric mucosa. They also occur in the central nervous system,
      as testicular lymphomas, in the lungs, or in the skin. Morphologically, they show
      the whole spectrum of peripheral B-blasts: centroblasts, immunoblasts, or
      plasmoblasts. Thus, there is no actual difference in their cytomorphological
      presentation compared to their nodal-and frequently systemic-counterparts.
      However, recent data point to profound differences in primary extranodal DLBCL
      compared to primary nodal tumors, as well as to each other, frequently relating
      to their molecular characteristics and especially implying organotypic features.
      These characteristics may relate to a particular organotypic site of origin, or
      the particular clinico-pathogenetic setting in which the tumors arise. This is
      exemplified in the description of the DLBCL subtypes as defined by the World
      Health Organization classification (mediastinal or intravascular B-cell lymphoma;
      primary effusion lymphoma). On the other hand, primary extranodal DLBCL are
      frequently characterized by a particular (cyto-)genetic constitution, often
      related to their site of origin. Finally, some preliminary data on gene
      expression profiling strongly argue in favor of particular gene signatures for
      primary extranodal DLBCL, and hence in favor of particular organotypic
      transformation pathways.

PMID- 17211672
TI  - Estimation of the proliferation and maturation functions in a physiologically
      structured model of thymocyte development. Function estimation in thymocyte
      model.
AB  - The thymus provides a stable microenvironment for post-natal thymocyte
      development that is finely regulated by a complicated network of cytokines,
      chemokines, cell-cell contacts, etc., the dysregulations of which contribute to
      many immunologic diseases including malignant lymphomas. A physiologically
      structured model in the form of first order partial differential equation (PDE)
      was developed to simulate the whole process. The combined effects of the thymic
      microenvironment were conceptualized into two (proliferation and differentiation)
      fields to serve as kernels of the PDE. In this paper, a novel method is developed
      to estimate the maturity-time structures of the two fields based solely on cell
      population data that are experimentally viable. Numerical examples demonstrate
      the effectiveness of the present method in revealing the two-dimensional
      (maturity and time) landscapes of the thymic microenvironment.

PMID- 17211675
TI  - Multidetector row CT detection of a post-traumatic chest wall pseudoaneurysm.

PMID- 17211673
TI  - Roles of putative His-to-Asp signaling modules HPT-1 and RRG-2, on viability and
      sensitivity to osmotic and oxidative stresses in Neurospora crassa.
AB  - Neurospora crassa has a putative histidine phosphotransfer protein (HPT-1) that
      transfers signals from 11 histidine kinases to two putative response regulators
      (RRG-1 and RRG-2) in its histidine-to-aspartate phosphorelay system. The hpt-1
      gene was successfully disrupted in the os-2 (MAP kinase gene) mutant, but not in
      the wild-type strain in this study. Crossing the resultant hpt-1; os-2 mutants
      with the wild-type or os-1 (histidine kinase gene) mutant strains produced no
      progeny with hpt-1 or os-1; hpt-1 mutation, strongly suggesting that hpt-1 is
      essential for growth unless downstream OS-2 is inactivated. hpt-1 mutation
      partially recovered the osmotic sensitivity of os-2 mutants, implying the
      involvement of yeast Skn7-like RRG-2 in osmoregulation. However, the rrg-2
      disruption did not change the osmotic sensitivity of the wild-type strain and the
      os-2 mutant, suggesting that rrg-2 did not participate in the osmoregulation.
      Both rrg-2 and os-2 single mutation slightly increased sensitivity to t-butyl
      hydroperoxide, and rrg-2 and hpt-1 mutations increased the os-2 mutant's
      sensitivity. Although OS-1 is considered as a positive regulator of OS-2 MAP
      kinase, our results suggested that HPT-1 negatively regulated downstream MAP
      kinase cascade, and that OS-2 and RRG-2 probably participate independently in the
      oxidative stress response in N. crassa.

PMID- 17211677
TI  - Lymph node metastasis detection of ovarian cancer by porphyrin fluorescence
      photodetection: case report.
AB  - The concept of intraoperative in vivo diagnosis and selective resection of
      infiltrated lymph nodes in ovarian cancer has not been evaluated despite the
      increased morbidity associated with pelvic and paraaortic lymph node dissection
      and its questionable therapeutic value. Fluorescence photodetection is based on
      the application of a photosensitizer relatively selective for malignant tissue,
      which after light activation of appropriate wavelength, shows fluorescence. Six
      hours after oral application of 10 mg/kg body weight 5-aminolevulinic acid, the
      abdominal cavity of a patient with suspicion of recurrent ovarian cancer was
      inspected using a laparoscope and blue light at 380-440 nm. Spectral measurements
      at a wavelength of 635 nm, multiple peritoneal biopsies, and lymph node excisions
      were performed. White light inspection and porphyrin fluorescence photodetection
      revealed no intraperitoneal metastases and multiple biopsies were negative.
      Fluorescence-positive lymph nodes were visible only in the left common iliac
      region and a specific porphyrin fluorescence peak could be detected. In contrary,
      no increased porphyrin fluorescence of intraperitoneal tissues or skin was seen.
      Fluorescence microscopy showed the characteristic red fluorescence in the
      infiltrated parts of the lymph node tissue by the papillary ovarian cancer.
      Histology of the other sites was negative. No systemic or cutaneous side effects
      were recorded. This data is a proof of the concept that porphyrin fluorescence
      guided lymph node metastasis detection is possible in ovarian cancer and should
      stimulate further research in this field.

PMID- 17211678
TI  - T helper 1 type cytokines polymorphisms: association with susceptibility to
      Behcet's disease.
AB  - The pathogenesis of Behcet's disease (BD) is not fully understood and
      immunological abnormalities and genetic factors have been investigated. Because
      serum concentrations of mainly T helper 1 (Th1) type cells have been reported to
      be increased in BD, we aimed to investigate whether certain cytokine
      polymorphisms might represent a risk factor for developing BD. We genotyped 80
      patients with BD and 105 healthy controls for interleukin (IL)-1 alpha (T/C 
      889), IL-1 beta (C/T -511, T/C +3962), IL-1R (C/T pst11970), IL-1RA (T/C
      mspa111100), IL-2 (T/G -330), IL-12 (C/A -1188), interferon (IFN)-gamma (A/T UTR
      5644), and TNF-alpha (G/A -238) polymorphisms. Analyses of cytokine polymorphisms
      were performed with PCR-SSP. The genotype and allele frequencies of the patients
      and controls were compared and the association between the polymorphisms of the
      cytokines with the clinical findings was investigated. Genotype distribution
      showed significant differences between the patients and the controls for the IL-1
      alpha -889, IL-1 beta -511, IL-1 beta +3962, IL-1R, IL-12, IFN- gamma, and TNF
      alpha cytokines. We didn't observe significant difference in genotypic
      frequencies of IL-1RA and IL-2 in our study. Comparison of the IL-1 alpha -889,
      IL 1 beta -511, and IL 1 beta +3962 genotype frequencies showed significant
      increase in CC genotype between the patients and the controls. The individuals
      with IL-1R TT polymorphism had a higher risk for BD compared to patients with
      CT/CC polymorphism. Comparison of IL-12, IFN- gamma, and TNF-alpha, genotype
      frequencies showed significant increase in CA, AA, and AA genotypes between the
      patients and controls, respectively. The frequencies of genotypes according to
      the clinical features of the patients with BD did not show a significant
      difference (p>0.05). Our study suggests that development of BD might be
      determined by various cytokine gene polymorphisms. However, further studies on
      larger numbers of cases are needed before definite conclusions can be drawn.

PMID- 17211679
TI  - Copper entry into human cells: progress and unanswered questions.
AB  - In this brief review we summarize what is known about the role of hCTR1 in
      mediating the entry of copper into human cells. There is a body of information
      that clearly identifies this protein as being a major source (though not the only
      source) of copper entry into human cells, and thus a crucial element of copper
      homeostasis. However, much remains that is poorly understood and key aspects of
      the physiological roles of hCTR1 and its regulation are only superficially
      appreciated. The particular characteristics of a transport process that in vivo
      involves the binding, transmembrane transport and release of a substrate that is
      not present in a free form in the intracellular or extracellular compartments
      poses particular challenges that are not encountered in the transport of more
      familiar physiologically important metal cations. Thus much of what we have
      learned about the more commonly encountered transported ions provides an
      inadequate model for studies of copper homeostasis. In this article we review
      progress made and identify the major questions that need to be resolved before an
      adequate description is attained of how copper entry into human cells is mediated
      and regulated by hCTR1.

PMID- 17211681
TI  - Iron homeostasis in the fission yeast Schizosaccharomyces pombe.
AB  - Schizosaccharomyces pombe has acquisition processes for iron, an essential
      nutrient. One pathway consists to produce, excrete, and capture siderophore-iron
      complexes. A second pathway requires enzymatic reduction of ferric iron at the
      cell surface prior to uptake by a permease-oxidase complex. Genes encoding
      proteins involved in iron assimilation are transcriptionally regulated as a
      function of iron availability. Under high iron conditions, the GATA-type
      regulator Fep1 represses the expression of iron uptake genes. The repressor
      function of Fep1 requires the presence of the Tup11 or Tup12 transcriptional co
      repressor. Under low iron conditions, two regulatory mechanisms occur. First, the
      iron transport genes are highly induced. Second, there is a transcription factor
      cascade implicating the heteromeric CCAAT-binding complex that turns off a set of
      genes encoding iron-utilizing proteins, presumably to avoid a futile expenditure
      of energy in producing iron-using proteins that lack the necessary cofactor to
      function. Thus, collectively, these regulatory responses to variations in iron
      concentrations ensure that iron is present within cells for essential biochemical
      reactions, yet prevent the accumulation of iron or iron-using proteins to
      deleterious levels.

PMID- 17211680
TI  - Coordinating responses to iron and oxygen stress with DNA and mRNA promoters: the
      ferritin story.
AB  - Combinations of DNA antioxidant response element and mRNA iron responsive element
      regulate ferritin expression in animals in response to oxidant and iron stress,
      or normal developmental signals. Ferritins are protein nanocages, found in
      animals, plants, bacteria, and archaea, that convert iron and oxygen to ferric
      oxy biominerals in the protein central cavity; the mineral traps potentially
      toxic reactants and concentrates iron for the future synthesis of other iron/heme
      proteins. Regulatory signals and the nanocage gene products are the same
      throughout biology, but the genetic mechanisms, DNA versus DNA + mRNA, vary. The
      number of genes, temporal regulation, tissue distribution in multi-cellular
      organisms, and gene product size (maxi-ferritins have 24 subunits and mini
      ferritins, or Dps proteins, have 12 subunits and are restricted to bacteria and
      archaea) suggest an overwhelming diversity and variability. However, common
      themes of regulation and function are described which indicate not only that the
      three-dimensional protein structure and the functions of the ferritins are
      conserved, but also that broad features of genetic regulation are conserved
      relative to organismal and/or community needs. The analysis illustrates the
      centrality of the ferritins to life with iron and oxygen and models how Nature
      harnesses potentially dangerous chemistry for biology.

PMID- 17211682
TI  - A structural perspective on copper uptake in eukaryotes.
AB  - Over a decade ago, genetic studies identified a family of small integral membrane
      proteins, commonly referred to as copper transporters (CTRs) that are both
      required and sufficient for cellular copper uptake in a yeast genetic
      complementation assay. We recently used electron crystallography to determine a
      projection density map of the human high affinity transporter hCTR1 embedded into
      a lipid bilayer. At 6 A resolution, this first glimpse of the structure revealed
      that hCTR1 is trimeric and possesses the type of radial symmetry that
      traditionally has been associated with the structure of certain ion channels such
      as potassium or gap junction channels. Representative for this particular type of
      architecture, a region of low protein density at the center of the trimer is
      consistent with the existence of a copper permeable pore along the center three
      fold axis of the trimer. In this contribution, we will briefly discuss how recent
      structure-function studies correlate with the projection density map, and provide
      a perspective with respect to the cellular uptake of other transition metals.

PMID- 17211683
TI  - Alpha-crystallin assisted refolding of enzyme substrates: optimization of
      external parameters.
AB  - alpha-Crystallin is known to act as a molecular chaperone by preventing the
      aggregation of partially unfolded substrate proteins. It is also known to assist
      the refolding of a number of denatured enzymes, but the activity yield is often
      less than 20%. In this paper, we have tried to tune the refolding ability of
      alpha-crystallin in vitro by optimizing various external parameters. We wanted to
      find out the best possible condition under which it can exhibit maximum refolding
      capacity. We found that under suitable condition in vitro alpha-crystallin can
      refold denatured malate dehydrogenase, carbonic anhydrase and lactate
      dehydrogenase to recover more than 40% activity. We also measured the effect of
      several external factors such as nucleotides, osmolytes, electrolytes,
      temperature etc. on the in vitro alpha-crystallin mediated reactivation of above
      stated enzymes. We found that nucleotides and electrolytes had little effect on
      the refolding ability of alpha-crystallin. However, in presence of different
      osmolytes, we found that its ability to reactivate denatured substrate proteins
      enhanced significantly. Refolding in presence of pre-incubated alpha-crystallin
      reveals that hydrophobicity had stronger influence on the refolding capacity of
      alpha-crystallin than its oligomeric size.

PMID- 17211685
TI  - George Albee and the nurturing spirit of primary prevention.

PMID- 17211684
TI  - Cloning, expression, purification, and characterization of biologically active
      recombinant hemagglutinin-33, type A botulinum neurotoxin associated protein.
AB  - Botulinum neurotoxin type A, the most toxic substance known to mankind, is
      produced by Clostridiurn botulinum type A as a complex with a group of neurotoxin
      associated proteins (NAPs) through polycistronic expression of a clustered group
      of genes. Hemagglutinin-33 (Hn-33) is a 33 kDa subcomponent of NAPs, which is
      resistant to protease digestion, a feature likely to be involved in the
      protection of the botulinum neurotoxin from proteolysis. In order to fully
      understand the function of Hn-33, large amounts of Hn-33 will be needed without
      dealing with biosafety risks to grow large cultures of C. botulinum. There are
      difficulties to clone the genes with the high A + T contents produced by C.
      botulinum. We report here for the first time using the Gateway technology to
      clone functional Hn-33 that has been expressed in E. coli. The yield of the
      recombinant Hn-33 was about 12 mg per liter of E. coli culture. The recombinant
      Hn-33 folds well in aqueous solution as shown with circular dichroism spectra,
      resists temperature-denaturation, is totally resistant to trypsin proteolysis
      despite the presence of cleavage sites on the molecular surface, and maintains
      its biological activities comparable to the native Hn-33 hemagglutination.

PMID- 17211686
TI  - George Wilson Albee.

PMID- 17211687
TI  - Memorial service for George W. Albee (1921-2006).

PMID- 17211689
TI  - Teaching adolescents and adults about adjudicative proceedings: a comparison of
      pre- and post-teaching scores on the MacCAT-CA.
AB  - The current study investigated whether teaching was associated with improved
      legal understanding among adolescents and adults. Participants included 927 youth
      and 466 young adults, who completed the MacArthur Competence Assessment Tool
      Criminal Adjudication, the Massachusetts Youth Screening Instrument-Second
      Version, and the Wechsler Abbreviated Scale of Intelligence. Adolescents aged 13
      and younger were less likely than older individuals to improve with teaching. IQ
      score was positively associated with improvements following teaching, and
      individuals from ethnic minority groups showed greater improvements following
      teaching than non-Hispanic Caucasians. The implications of these findings are
      discussed.

PMID- 17211688
TI  - Risk assessment for juvenile justice: a meta-analysis.
AB  - Risk assessment instruments are increasingly employed by juvenile justice
      settings to estimate the likelihood of recidivism among delinquent juveniles. In
      concert with their increased use, validation studies documenting their predictive
      validity have increased in number. The purpose of this study was to assess the
      average predictive validity of juvenile justice risk assessment instruments and
      to identify risk assessment characteristics that are associated with higher
      predictive validity. A search of the published and grey literature yielded 28
      studies that estimated the predictive validity of 28 risk assessment instruments.
      Findings of the meta-analysis were consistent with effect sizes obtained in
      larger meta-analyses of criminal justice risk assessment instruments and showed
      that brief risk assessment instruments had smaller effect sizes than other types
      of instruments. However, this finding is tentative owing to limitations of the
      literature.

PMID- 17211690
TI  - The impact of negative forensic evidence on mock jurors' perceptions of a trial
      of drug-facilitated sexual assault.
AB  - Legal concerns with regard to the adverse impact of a negative toxicological
      screening for date-rape drugs in a case of drug-facilitated sexual assault (DFSA)
      were the focus of a recent Canadian case (R. v. Alouache, 2003). To assess the
      impact of a negative forensic report, as well as the impact of expert testimony
      explaining the many factors that may contribute to a negative outcome,
      participants (N=171) received a written trial stimulus in which the forensic
      evidence (negative report, negative report plus expert testimony, no negative
      report and no expert testimony control) and the complainant's beverage
      consumption (alcohol, cola) were systematically varied. Results indicate that a
      negative finding in the absence of expert testimony produced greater verdict
      leniency and more favourable evaluations of the defendant's case. In contrast, no
      differences were found between the case in which the expert testified and a case
      in which the negative report and expert testimony were omitted.

PMID- 17211691
TI  - Cues to deception and ability to detect lies as a function of police interview
      styles.
AB  - In Experiment 1, we examined whether three interview styles used by the police,
      accusatory, information-gathering and behaviour analysis, reveal verbal cues to
      deceit, measured with the Criteria-Based Content Analysis (CBCA) and Reality
      Monitoring (RM) methods. A total of 120 mock suspects told the truth or lied
      about a staged event and were interviewed by a police officer employing one of
      these three interview styles. The results showed that accusatory interviews,
      which typically result in suspects making short denials, contained the fewest
      verbal cues to deceit. Moreover, RM distinguished between truth tellers and liars
      better than CBCA. Finally, manual RM coding resulted in more verbal cues to
      deception than automatic coding of the RM criteria utilising the Linguistic
      Inquiry and Word Count (LIWC) software programme. In Experiment 2, we examined
      the effects of the three police interview styles on the ability to detect
      deception. Sixty-eight police officers watched some of the videotaped interviews
      of Experiment 1 and made veracity and confidence judgements. Accuracy scores did
      not differ between the three interview styles; however, watching accusatory
      interviews resulted in more false accusations (accusing truth tellers of lying)
      than watching information-gathering interviews. Furthermore, only in accusatory
      interviews, judgements of mendacity were associated with higher confidence. We
      discuss the possible danger of conducting accusatory interviews.

PMID- 17211692
TI  - Prevalence of hepatitis B virus genotype D in precore mutants among chronic liver
      disease patients from New Delhi, India.
AB  - Hepatitis B is one of the most important causes of chronic viral hepatitis world
      wide. Mutations in the precore region of the hepatitis B virus (HBV) genome are
      frequently found in hepatitis B envelope antigen-negative cases. Data from India
      on the HBV genotype-associated distribution of precore mutations are limited. Our
      objective in this study was to genotype and detect the precore mutant with a
      point mutation from G to A at nucleotide 1896 using ligase chain reaction (LCR)
      and direct sequencing. A total of 115 cases of chronic liver disease were
      screened. The cases were evaluated on the basis of history, clinical examination,
      liver function profile, and serological test for HBV infection, which includes
      HBsAg, anti HBcIgG, HBeAg using commercially available ELISA kits. The cases,
      which were HBeAg+, HBeAg-, and HBV DNA+, were subjected to LCR and confirmed by
      direct sequencing. Of 115 chronic liver disease cases, 50 (43.5%) cases were HBV
      DNA positive. All cases were subjected to LCR; 11 (22%) cases confirmed the
      presence of precore mutants, while the remaining 39 (78%) were classified as the
      wild form of the virus. HBV genotyping by direct sequencing revealed that
      genotype D was predominant in both wild and mutant forms of the virus. We
      conclude that the HBV genotype distribution was not significantly different
      between precore mutants and the wild form of the virus (P>0.05). North Indian
      patients with genotype D were more likely to have persistent HBV infection with
      precore mutants. HBV genotypes correlate with the clinical outcome of chronic HBV
      infection.

PMID- 17211693
TI  - Inhibition of neutrophil activation by lafutidine, an H2-receptor antagonist,
      through enhancement of sensory neuron activation contributes to the reduction of
      stress-induced gastric mucosal injury in rats.
AB  - Sensory neuron activation reduces water-immersion restraint stress (WIR)-induced
      gastric mucosal injury by inhibiting neutrophil activation through increase in
      endothelial production of prostacyclin. This study was designed to examine
      whether lafutidine, which is an H(2)-receptor antagonist and activates sensory
      neurons, inhibits neutrophil activation, thereby reducing WIR-induced gastric
      mucosal injury. Lafutidine enhanced WIR-induced increases in gastric tissue
      levels of calcitonin gene-related peptide (CGRP) and 6-keto-PGF(1alpha), a stable
      metabolite of prostacyclin, whereas famotidine, another H(2)-receptor antagonist,
      did not. Such lafutidine-induced increases in gastric tissue levels of 6-keto
      PGF(1alpha) were reversed by pretreatment with capsazepine, an inhibitor of
      sensory neuron activation, CGRP(8-37), a CGRP antagonist, and indomethacin.
      Lafutidine inhibited acid-induced exacerbation of gastric mucosal injury in
      animals subjected to WIR by inhibiting neutrophil activation, whereas famotidine
      did not. Lafutidine synergistically increased CGRP release from isolated rat
      dorsal root ganglion neurons in the presence of anandamide, but famotidine did
      not. These observations suggest that lafutidine might reduce WIR-induced gastric
      mucosal injury not only by inhibiting acid secretion but also by inhibiting
      neutrophil activation through enhancement of sensory neuron activation.

PMID- 17211694
TI  - EUS yield in evaluating biliary dilatation in patients with normal serum liver
      enzymes.
AB  - The finding of common bile duct (CBD) dilatation on abdominal imaging frequently
      results in additional testing. It has been our impression that endoscopic
      ultrasound (EUS) evaluation of a dilated CBD is a low-yield examination in the
      setting of normal serum liver enzymes. We therefore sought to evaluate the EUS
      yield in evaluating CBD dilatation in patients with normal as compared to
      elevated serum liver enzymes. A retrospective review was performed to identify
      patients referred for EUS evaluation of a dilated CBD in the absence of obvious
      pathology on prior imaging. Charts were reviewed for patient symptoms, presence
      of elevated serum liver enzymes, imaging studies before EUS, and EUS findings.
      Exclusion criteria included clinical jaundice, known biliary stricture, mass
      lesion or stone, and previously sphincterotomy and/or stent placement. Forty
      seven patients were identified: 32 with normal and 15 with elevated serum liver
      enzymes. There was no difference in mean CBD diameter between these two groups
      (8.51 vs. 8.79 mm, p=0.854). Of the entire group, 15 patients had undergone prior
      magnetic resonance cholangiopancreatography (MRCP); an additional 7 patients had
      undergone prior endoscopic retrograde cholangiopancreatography (ERCP). EUS
      findings to explain CBD dilatation were found more commonly in patients with
      elevated compared with normal serum liver enzymes (53% vs. 6%, p=0.001).
      Periampullary diverticula and choledocholithiasis were the most common findings;
      of 32 patients with normal serum liver enzymes, one periampullary diverticulum
      and one CBD stone were found, respectively. The CBD stone had been missed by
      prior MRCP examination. Of 15 patients with elevated serum liver enzymes, there
      were 3 cases of choledocholithiasis, 4 periampullary diverticula, and 1 ampullary
      tumor. EUS should be the test of choice for further evaluation of CBD dilatation
      when index imaging is normal. Although the EUS yield is low in cases of biliary
      dilatation in the setting of normal serum liver enzymes, its preferential use
      would potentially avoid unnecessary MRCP and ERCP.

PMID- 17211695
TI  - Effect of antisecretory therapy on atypical symptoms in gastroesophageal reflux
      disease.
AB  - The effect of proton pump inhibitor (PPI) therapy on extraesophageal or atypical
      manifestations of gastroesophageal reflux disease (GERD) remains unclear. This
      study aimed to evaluate the prevalence of atypical manifestations in patients
      with acid reflux disease and the effect of PPI treatment. Patients with symptoms
      and signs suggestive of reflux were enrolled. Erosive esophagitis was stratified
      using the Los Angeles classification. Demographic data and symptoms were assessed
      using a questionnaire and included typical symptoms (heartburn, regurgitation,
      dysphagia, odynophagia), and atypical symptoms (e.g., chest pain, sialorrhea,
      hoarseness, globus sensation, chronic coughing, episodic bronchospasm, hiccup,
      eructations, laryngitis, and pharyngitis). Symptoms were reassessed after a 3
      month course of b.i.d. PPI therapy. A total of 266 patients with a first
      diagnosis of GERD (erosive, 166; non-erosive, 100) were entered in the study.
      Presentation with atypical symptoms was approximately equal in those with erosive
      GERD and with non-erosive GERD, 72% vs 79% (P = 0.18). None of the study
      variables showed a significant association with the body mass index. PPI therapy
      resulted in complete symptom resolution in 69% (162/237) of the participants, 12%
      (28) had improved symptoms, and 20% (47) had minimal or no improvement. We
      conclude that atypical symptoms are frequent in patients with GERD. A trial of
      PPI therapy should be considered prior to referring these patients to
      specialists.

PMID- 17211696
TI  - Effect of naloxone-3-glucuronide and N-methylnaloxone on the motility of the
      isolated rat colon after morphine.
AB  - The effect of the opioid antagonists naloxone-3-glucuronide and N-methylnaloxone
      on rat colon motility after morphine stimulation was measured. The rat model
      consisted of the isolated, vascularly perfused colon. The antagonists (10(-4) M,
      intraluminally) and morphine (10(-4) M, intra-arterially) were administered from
      20 to 30 and from 10 to 50 min, respectively. Colon motility was determined by
      the luminal outflow. The antagonist concentrations in the luminal and venous
      outflow were measured by high-performance liquid chromatography. Naloxone-3
      glucuronide and N-methylnaloxone reversed the morphine-induced reduction of the
      luminal outflow to baseline within 10 and 20 min, respectively. These antagonists
      were then excreted in the luminal outflow and could not be found in the venous
      samples. Naloxone, produced by hydrolysis or demethylation, was not detectable.
      In conclusion, highly polar naloxone derivatives peripherally antagonize the
      motility-lowering effect of morphine in the perfused isolated rat colon, are
      stable, and are not able to cross the colon-mucosal blood barrier.

PMID- 17211697
TI  - Effect of acute gastric electrical stimulation on the systemic release of
      hormones and plasma glucose in dogs.
AB  - This study evaluated the effect of gastric electrical stimulation (GES) with
      various parameters on plasma concentrations of satiety-related peptides and
      glucose. GES was performed in nine healthy dogs via electrodes implanted in the
      middle of the lesser curvature. Four sessions were performed in each animal:
      control, stimulation with IGS (implantable gastric stimulation for obesity, 0.3 m
      sec), modified IGS (2 msec), and long pulses (300 msec). Blood samples were
      collected at 15 and 0 min before the meal and at 15, 30, and 60 min after the
      meal. GES was initiated 30 min before the first blood sample and maintained
      throughout collection. Plasma ghrelin, leptin, insulin and glucose were measured.
      The total AUCs of plasma ghrelin and leptin were not significantly affected by
      GES. The total AUC of plasma insulin was significantly lower with IGS and long
      pulse parameters (P < 0.05). The total AUC for plasma glucose was significantly
      lower in sessions with long pulses and modified IGS parameters (P < 0.05). We
      conclude that acute GES is able to change the release of some satiety-related
      peptides. Whether this is associated with the changed eating behavior and weight
      loss in obese patients needs further investigation.

PMID- 17211698
TI  - Electroacupuncture and moxibustion promote neutrophil apoptosis and improve
      ulcerative colitis in rats.
AB  - The purpose of this study was to investigate the effect of electroacupuncture
      (EA) and moxibustion on promoting neutrophil apoptosis. A rat model of ulcerative
      colitis was established by immunological methods using human colonic mucosa as
      antigen. All rats were randomly assigned to the model control (MC) group, EA
      group, or herbs-partition moxibustion (HPM) group. Normal rats were used as the
      normal control (NC) group. Peripheral blood mononuclear cells (PBMCs) from all
      rats and circular neutrophils from NC rats were isolated and cultured. Circular
      neutrophils were incubated with cultured supernatants of PBMCs from the MC, NC,
      EA, and HPM groups, respectively. Neutrophil apoptosis and concentration of IL
      1beta, IL-6, and TNF-alpha from induced cultured supernatants were detected by
      cell cytometry and ELISA, respectively. Compared with MC, HPM, and EA rats,
      mucosal inflammatory lesions abated remarkably. No hyperemia or edema was seen in
      the lamina propria, inflammatory cell infiltration decreased, neutrophil
      infiltration disappeared, and epithelial and crypt cells proliferated and
      repaired the ulceration of the mucosa. Neutrophil apoptosis was promoted.
      Concentrations of IL-1beta, IL-6, and TNF-alpha were decreased, respectively. We
      conclude that EA and HPM therapy can improve ulcerative colitis rats
      histologically, which may be due to promoting neutrophil apoptosis and down
      regulating monocyte cytokines. EA and moxibustion are effective for treating
      ulcerative colitis.

PMID- 17211699
TI  - Failure of Synbiotic 2000 to prevent postoperative recurrence of Crohn's disease.
AB  - Complications of Crohn's disease (CD) lead to surgery in about 70-90% of
      patients. The majority of patients suffer from relapse of the disease. Colonic
      bacteria are essential to the development of CD. Therefore, a rationale exists in
      trying to prevent relapse by manipulation of gut microflora. This is feasible by
      treatment with probiotics or antibiotics. Synbiotic 2000 is a cocktail containing
      4 probiotic species and 4 prebiotics. It is rational to pursue that it could be
      effective in preventing postoperative disease. We sought to check weather
      treatment with Synbiotic 2000 could prevent postoperative recurrence in patients
      with CD. This was a prospective multicenter, randomized study. Patients were
      randomized to active treatment or placebo in a 2:1 ratio. Follow-up consisted of
      endoscopic, clinical, and laboratory parameters. Thirty patients were enrolled.
      No differences were found between the 2 treatment groups regarding gender, age at
      diagnosis, age at surgery, weight, smoking status, type of disease, length of the
      resected segment, or medical treatment prior to surgery. No difference in either
      endoscopic or clinical relapse rate was found between patients treated with once
      daily dose of Synbiotic 2000 or placebo. In our small study, Synbiotic 2000 had
      no effect on postoperative recurrence of patients with CD. Larger studies in
      patients with the inflammatory type of CD undergoing surgery, using higher doses
      of probiotics cocktail might prove effective.

PMID- 17211701
TI  - Incidence of IBS in a cohort of people with asthma.
AB  - We conducted a study to examine the relation of asthma and its treatment to
      irritable bowel syndrome (IBS). We identified cohorts of members with and without
      asthma from January 1996 though June 2002 and calculated rates of IBS in both
      cohorts. In a nested case-control study, we calculated odds ratios for oral
      steroid dispensing before IBS onset. To address differential IBS detection, we
      conducted a quantitative sensitivity analysis. We identified 91,237 people with
      asthma and sample of 24,518 people without asthma. There was a 20% increase in
      the incidence of IBS among people with asthma (standardized morbidity ratio =
      1.2; 95% CI, 1.0-1.5), and no association between oral steroids and IBS among
      people with asthma (OR = 1.0; 95% CI, 0.9-1.1.) Misclassification of IBS would
      have biased the rate ratio toward the null. We observed a small increase in IBS
      among people with asthma, and no association between oral steroids and IBS onset
      among asthma patients.

PMID- 17211700
TI  - Changes in bowel function: pregnancy and the puerperium.
AB  - Pregnancy is a time when women are susceptible to bowel habit perturbations. The
      purpose of this study was to provide new baseline data for a range of bowel habit
      parameters. Prospective 7-day bowel habit diaries were completed during each of
      the three trimesters of pregnancy and after birth. Sensations of incomplete
      evacuation and time spent defecating were significantly increased during all
      three trimesters of pregnancy compared with after birth (P < 0.05). Symptoms of
      urgency were higher in nonlactating mothers (41% of occasions) compared with
      lactating women (17% pf occasions) (P=0.07). This study has confirmed the
      importance of investigating a range of bowel habit parameters during and after
      pregnancy-investigation of constipation per se may obscure changes in individual
      bowel habit parameters.

PMID- 17211702
TI  - Feasibility and acceptance of a home telemanagement system in patients with
      inflammatory bowel disease: a 6-month pilot study.
AB  - Our purpose was to assess the acceptance and feasibility of a home telemanagement
      system (HAT) in inflammatory bowel disease (IBD). The HAT consists of a laptop
      and a scale. Subjects were required to complete weekly self-testing for 6 months.
      Disease activity, quality of life, and knowledge were assessed at baseline and 6
      months. Attitudinal surveys were completed at 6 months. Twenty-five subjects
      completed the study. Ninety-one percent of patients thought that self-testing was
      not complicated. Eighty-six percent said that self-testing did not interfere with
      their usual activities. Ninety-one percent of patients would consider using a HAT
      in the future. Adherence with self-testing was 91%. Improvements in disease
      activity and quality of life, and significant improvements in knowledge, were
      observed after implementation of the HAT. The HAT is feasible and accepted in
      IBD. We predict that the HAT will positively affect adherence, monitoring, and
      patient education, resulting in improved disease activity and quality of life.

PMID- 17211703
TI  - A retrospective, case-control pilot study of the natural history of pediatric
      gastroesophageal reflux.
AB  - The duration of gastroesophageal reflux disease (GERD) is an important factor in
      the development of esophageal complications. The objective of this study was to
      examine in a retrospective, case-controlled manner the prevalence of GERD in
      adults who were diagnosed with GERD in infancy or early childhood. Infants and
      children with nonsyndromic GERD diagnosed by an experienced pediatric
      gastroenterologist from 1976 to 1980 and control subjects seen for well-child
      care from 1980 to 1985 were included in this study. The subjects were located and
      contacted by telephone or mail and administered a brief structured questionnaire
      relating to their current history of GERD. GERD-A was defined as weekly heartburn
      or regurgitation of any severity, and GERD-B was defined as monthly heartburn or
      regurgitation greater than mild in severity. Sixty-five participants (31 patients
      and 34 controls) returned completed questionnaires and were subdivided into the
      three study groups as follows: Infant (15), Child (16), and Control (34). The
      prevalence of adulthood GERD-A was 13, 31, and 21% in the Infant, Child, and
      Control groups, respectively. Similarly, the prevalence of adulthood GERD-B was
      20%, 44%, and 24%, respectively. The Child group tended to report more severe
      heartburn than the other groups. The Infant group tended to report more frequent
      regurgitation, and the Child group also reported a higher prevalence of nocturnal
      heartburn and more frequent use of GERD medications, although these were not
      statistically significant. These data suggest that pediatric GER is a
      heterogeneous disorder and that GERD occurring after infancy may be more
      predictive of the presence of GERD during adulthood. Longitudinal follow-up of a
      larger number of children is needed to answer the question of when classic
      adulthood GERD begins.

PMID- 17211704
TI  - Liver biopsy: is the pain for real or is it only the fear of it?
AB  - Although percutaneous liver biopsy (PLB) has very low mortality and morbidity
      rates, it often is considered painful and frightening by the patients. This study
      was designed to grade the intensity of pain expected before the procedure and
      experienced during the procedure, and whether there is any correlation between
      pain and the emotional state of the patient. A total of 118 consecutive patients
      (aged 19-68 (mean, 44) years), who were undergoing PLB for the first time, were
      included in the study. Visual Analogue Scale (VAS) was used before the procedure,
      after the procedure to grade the degree of pain expected, and the degree of the
      pain experienced respectively. All the patients were evaluated by a questionnaire
      for their personality and emotional situation by using the Minnesota Multiphasic
      Personality Inventory Somatization Sub-scale (MMPI-SS). Mean VAS score for
      expected pain before the procedure was 60+/-20 and for the pain experienced
      during the procedure was 22+/-16 (P < 0.0001). Although the expected pain scores
      of female patients were significantly higher than males (66+/-22 vs. 55+/-17;
      P=0.003), there was no difference between female and male patients in the
      experienced pain scores. The procedure of PLB is expected to be more painful than
      it really is by the patients, especially by females. Calming the patients by
      informing them about the procedure and their diseases will probably diminish the
      expected pain.

PMID- 17211705
TI  - Which has superior acid-suppressive effect, 10 mg omeprazole once daily or 20 mg
      famotidine twice daily? Effects of single or repeated administration in Japanese
      Helicobacter pylori-negative CYP2C19 extensive metabolizers.
AB  - Low-dose omeprazole is superior to full-dose famotidine in maintenance therapy
      for gastroesophageal reflux disease, whereas "on-demand" famotidine is more
      effective for relief of episodes of heartburn. To explain this apparent
      discrepancy, intragastric pH was measured for 24-hr seven times in eight Japanese
      Helicobacter pylori-negative cytochrome P450 2C19 extensive metabolizers; on Days
      1, 8, and 15 of repeated administration of 10 mg of omeprazole once daily and of
      20 mg of famotidine twice daily and before medication. During repeated
      administration of omeprazole, mean intragastric pH and % time that intragastric
      pH > 4.0 were significantly higher and became greater. With famotidine, although
      these parameters were significantly higher, the degrees became smaller.
      Consequently, acid-suppressive effect was in the order; omeprazole < famotidine
      on Day 1, omeprazole approximately famotidine on Day 8, and omeprazole
      >famotidine on Day 15. This discrepancy possibly results from the "potentiation"
      of acid-suppressive effect of omeprazole and the "tolerance" phenomenon in
      respect to famotidine.

PMID- 17211707
TI  - The activity of class I, III, and IV of alcohol dehydrogenase isoenzymes and
      aldehyde dehydrogenase in gastric cancer.
AB  - The metabolism of cancer is in many way different than in healthy cells.
      Increased metabolism of several carcinogenic substances may take place in cancer
      cells. The one of them was ethanol, that is oxidized by alcohol dehydrogenase
      (ADH) to high concentration of acetaldehyde, a toxic and carcinogenic compound.
      The enzyme responsible for oxidation of acetaldehyde is aldehyde dehydrogenase
      (ALDH). The aim of this study was to compare the capacity for ethanol metabolism
      measured by ADH isoenzymes and ALDH activity between gastric cancer and normal
      gastric mucosa. Total ADH activity was measured by photometric method with p
      nitrosodimethylaniline (NDMA) as a substrate and ALDH activity by the
      fluorometric method with 6-methoxy-2-naphtaldehyde as a substrate. For the
      measurement of the activity of class I isoenzymes, we used fluorometric methods,
      with class-specific fluorogenic substrates. The activity of class III ADH was
      measured by the photometric method with n-octanol and class IV with m
      nitrobenzaldehyde as a substrate. The samples were taken surgically during
      routine operations of gastric carcinomas from 55 patients. The activities of
      total ADH, and the most important in gastric mucosa, class IV ADH were
      significantly higher in cancer cells than in healthy tissues. The other tested
      classes of ADH and ALDH showed a tendency toward higher activity in cancer than
      in healthy mucosa. The activities of all tested enzymes and isoenzymes were not
      significantly higher in men than in women in wither gastric cancer tissues or
      normal mucosa. The increased ADH IV activity may be 1 of the factors intensifying
      carcinogenesis by the increased ability to acetaldehyde formation from ethanol.

PMID- 17211706
TI  - Audit of constipation in a gastroenterology referral center.
AB  - This study was designed to assess the various subtypes of functional constipation
      in a referral gastrointestinal center of a Latino-American country. All patients
      referred for evaluation of constipation during a 10-year period were audited, and
      those with functional constipation according to Rome I criteria classified by
      physiologic tests of colonic transit, as well as tests of anorectal and pelvic
      floor function. More than 70% of patients with functional constipation had
      evidence of pelvic floor dysfunction, whereas those with slow transit and
      constipation-predominant irritable bowel syndrome subtypes were less frequently
      represented. Even in a setting different from those most frequently reported in
      the literature, pelvic floor dysfunction represents the most common cause of
      functional constipation. Simple, physiologic testing is needed and useful for the
      diagnosis. This fact has therapeutic implications, especially because many such
      patients may benefit from biofeedback.

PMID- 17211708
TI  - Serum ferritin, vitamin B(12), folate, and zinc levels in children infected with
      Helicobacter pylori.
AB  - We sought to explore the relationship between Helicobacter pylori infection and
      serum ferritin, vitamin B(12), folate, and zinc status among children. Fifty
      patients aged 5-18 years who underwent upper gastrointestinal endoscopy because
      of dyspeptic symptoms, were studied, prospectively. Patients were grouped as H.
      pylori positive (group 1, n=32) or H. pylori negative (group 2, n=18) by
      histopathologic examination and rapid urease test. Fasting serum ferritin,
      vitamin B(12), folate, and zinc levels of patients were measured. Both groups
      were indifferent according to age, gender, height standard deviation score
      (H(SDS)), and weight standard deviation score (W(SDS)). Serum ferritin levels
      were 33+/-26 and 50+/-46 ng/mL (P=.098), vitamin B(12) levels were 303+/-135 and
      393+/-166 pg/mL (P=.042), folate levels were 9.64+/-3.2 and 9.61+/-2.8 ng/mL
      (P=.979), and zinc levels were 95+/-48 and 87+/-31 mug/dL (P=.538), in groups 1
      and 2, respectively. Ferritin levels of 14 (43.8%) patients in group 1 and 6
      (33.3%) patients in group 2 were below the normal range (P=.470). Serum vitamin
      B(12) levels of 9 children (28%) in group 1 and 2 children (11%) in group 2 were
      below the normal range (P=.287). The findings of the present study suggest that
      H. pylori infection has a negative effect on serum ferritin and vitamin B(12)
      levels in children. This negative effect on vitamin B(12) levels is rather marked
      in contrast to that on ferritin levels. H. pylori infection has no significant
      effect on serum folate or zinc levels among children.

PMID- 17211710
TI  - Predictors and noninvasive identification of severe liver fibrosis in patients
      with chronic hepatitis C.
AB  - Diagnosis of severe fibrosis (stages III and IV) in hepatitis C has clinical
      implications. Our objective was to distinguish independent predictors of severe
      fibrosis and use them to identify patients with severe fibrosis without a liver
      biopsy. One hundred ninety-nine hepatitis C patients were included in the initial
      analysis to identify predictors of severe fibrosis. Univariate and multivariate
      analyses of 26 predetermined variables for significance in predicting severe
      fibrosis were performed. Based on the coefficient regression and P values, a
      scoring system was developed and applied to a second independent cohort (137
      patients) for validation. In multivariate analysis, low platelet count, low
      albumin, aspartate transaminase level, history of blood transfusion, and
      hepatitis B core antibody were significant independent predictors of severe
      fibrosis. A scoring system (range, 0-9) was developed from the three variables
      with the lowest P values (platelet count, aspartate transaminase, and albumin). A
      cutoff point of 4 had 99% specificity and 94% positive predictive value. A cutoff
      point of 2 had 87% sensitivity and 95% negative predictive value. We conclude
      that severe fibrosis in hepatitis C may potentially be identified with a high
      degree of certainty in a substantial number of patients with a simple noninvasive
      scoring system.

PMID- 17211709
TI  - Prognostic significance of RCAS1 expression in relation to the infiltration of
      dendritic cells and lymphocytes in patients with esophageal carcinoma.
AB  - RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) expression was
      determined in 107 esophageal carcinoma patients by immunohistochemical procedures
      and compared with tumor infiltrating lymphocyte (TIL) and dendritic cell (DC)
      infiltration to evaluate the effect of RCAS1 on immune responses in esophageal
      carcinoma. RCAS1 immunoreactivity was detected in 59 of 107 patients (55.1%).
      RCAS1 expression was significantly correlated with the depth of invasion, lymph
      node metastasis, and histologic stage. RCAS1 expression tended to be correlated
      with a lower TIL density in tumors with marked DC infiltration. The survival time
      for patients with RCAS1-negative tumors was significantly longer than that for
      patients with RCAS1-positive tumors. Especially, the prognosis was predicted by
      RCAS1 in cases with marked DC infiltration. Multivariate analysis revealed that
      RCAS1 expression was an independent prognostic factor. RCAS1 expression may play
      an important role in evading the immunological defense mechanisms in esophageal
      carcinoma.

PMID- 17211711
TI  - Morbidity and mortality of laparoscopy-assisted gastrectomy with extraperigastric
      lymph node dissection for gastric cancer.
AB  - Gastrectomy with extraperigastric lymph node dissection has not been generally
      acceptable because of increased morbidity and mortality in some Western
      countries. Recently, many surgeons have become interested in laparoscopic gastric
      surgery for malignant disease as well as benign lesions because laparoscopic
      surgery itself has been shown to have many advantages over open surgery. The aims
      of this study are to evaluate the incidence and nature of operative morbidity and
      mortality after laparoscopy-assisted gastrectomy (LAG) with extraperigastric
      lymph node dissection with respect to surgical experience and to identify factors
      predictive of complications and death. We reviewed the surgical outcomes of LAG
      with extraperigastric lymph node dissection in 140 consecutive gastric cancer
      patients. Clinicopathologic characteristics, operative outcomes, and
      postoperative morbidities and mortalities were compared after dividing the 140
      patients into early (1-70) and late (71-140) groups. And risk factors for
      morbidity and mortality were identified by multivariate logistic regression
      analysis. The overall operative morbidity and mortality rates were 18.6% and
      0.7%, respectively. Thirty postoperative complications occurred in 26 patients.
      The minor surgical complication rate in the late group was significantly lower
      than that in the early group (P = 0.0349). According to univariate and
      multivariate analyses to evaluate the independent predictor of a higher operative
      morbidity rate, no factor was significantly associated with operative morbidity.
      We conclude that LAG with extraperigastric lymph node dissection is a technically
      feasible and acceptable surgical modality for gastric cancer and low morbidity
      and mortality rates for this procedure can be accomplished by experienced
      laparoscopic gastric surgeons at large-volume hospitals.

PMID- 17211712
TI  - Impact of anal incontinence on psychosocial function and health-related quality
      of life.
AB  - The relationship among the frequency of anal incontinence (AI), psychosocial
      factors, and health-related quality of life (HRQOL) was evaluated. Consecutive
      patients (n=280) completed a bowel symptom questionnaire, the Symptom Checklist
      90 -- Revised (SCL 90-R), and an assessment of HRQOL. Group 1 had no
      incontinence, Group 2 had AI less than once per week, and Group 3 experienced AI
      more than once per week. Multivariate analyses were used to evaluate the
      relationship among symptoms, the SCL-90-R subscales, and HRQOL. Group 3 reported
      more frequent stools than the other groups. Significant psychological distress
      was present in both incontinent groups compared to Group 1 (P=0.002). A reduction
      in overall HRQOL was also seen in the incontinent groups. Depression was
      inversely correlated with QOL-Satisfaction and QOL-Ratings and positively
      correlated with QOL-Interference. AI was associated with impaired psychosocial
      function and decreased HRQOL. The frequency of AI was associated with increased
      HRQOL-Interference, but minimally with the degree of psychosocial impairment.

PMID- 17211713
TI  - Estimation of population pharmacokinetic parameters of saquinavir in HIV patients
      with the MONOLIX software.
AB  - In nonlinear mixed-effects models, estimation methods based on a linearization of
      the likelihood are widely used although they have several methodological
      drawbacks. Kuhn and Lavielle (Comput. Statist. Data Anal. 49:1020-1038 (2005))
      developed an estimation method which combines the SAEM (Stochastic Approximation
      EM) algorithm, with a MCMC (Markov Chain Monte Carlo) procedure for maximum
      likelihood estimation in nonlinear mixed-effects models without linearization.
      This method is implemented in the Matlab software MONOLIX which is available at
      http://www.math.u-psud.fr/~lavielle/monolix/logiciels. In this paper we apply
      MONOLIX to the analysis of the pharmacokinetics of saquinavir, a protease
      inhibitor, from concentrations measured after single dose administration in 100
      HIV patients, some with advance disease. We also illustrate how to use MONOLIX to
      build the covariate model using the Bayesian Information Criterion. Saquinavir
      oral clearance (CL/F) was estimated to be 1.26 L/h and to increase with body mass
      index, the inter-patient variability for CL/F being 120%. Several methodological
      developments are ongoing to extend SAEM which is a very promising estimation
      method for population pharmacockinetic/pharmacodynamic analyses.

PMID- 17211714
TI  - Administrative barriers to the adoption of high-quality mental health services
      for children in foster care: a national study.
AB  - While the need to provide appropriate mental health services to children in
      foster care is well recognized, there is little information on administrative
      barriers to assuring that such services are provided. This article presents
      results from a national survey of mental health agencies to profile their
      awareness of currently available practice standards, the roles these standards
      play in guiding practice of mental health agencies, common reimbursement
      strategies in use for mental health services, and collaborations between mental
      health and child welfare agencies that enhance children's access to appropriate
      mental health care. Implications and recommendations for mental health
      policymakers are discussed.

PMID- 17211715
TI  - Why some clinicians use outcome measures and others do not.
AB  - Due to their potential as helpful clinical tools, it is necessary to understand
      the reasons why certain practitioners are currently using outcome measures and
      certain others are not. This study investigated the reasons why clinicians use
      outcome measures based upon factors such as work setting, theoretical orientation
      and source of payment. Similar analyses were conducted for reasons that
      clinicians do not use outcome measures. Findings suggest that several practical
      barriers are the primary reasons for not using outcome measures, although a
      subset of clinicians have additional concerns. Results also emphasized the need
      for clinicians to be trained on how to maximize the clinical benefits of
      formalized outcome assessment.

PMID- 17211716
TI  - The relationship of antipsychotic medication class and adherence with treatment
      outcomes and costs for Florida Medicaid beneficiaries with schizophrenia.
AB  - While some studies show a significant advantage in adherence rates with use of
      atypical versus typical antipsychotic medication, others show no advantage or
      mixed results (Jones et al. (2006). Archives of General Psychiatry, 63, 1079
      1087; Rosenheck, (2006). Archives of General Psychiatry, 63, 1074-1076). This
      study examined treatment outcomes and costs associated with adherence rates by
      antipsychotic medication class for adult Medicaid beneficiaries in Florida
      diagnosed with schizophrenia. Outcomes examined include arrests, involuntary
      commitments, and physical and behavioral healthcare costs. Study findings
      demonstrate that medication adherence for persons with schizophrenia may be as
      important to treatment costs and benefits as the class of medication used.

PMID- 17211717
TI  - How parents seek help for children with mental health problems.
AB  - Parents seeking help for their child's mental health problem face a complicated
      system of services. We examined how parents navigate the various services
      available. Sixty parents contacting a children's mental health center were
      interviewed regarding their efforts and rationale in seeking help for their
      child. On average, in the year prior to the interview parents sought help for two
      different child problems, contacted five different agencies or professionals for
      help, and parents and/or children received two different treatments. One fifth of
      the time parents said they accepted treatments that they did not want. Almost all
      parents (87%) were simultaneously in contact with more than one agency at some
      point within the previous year. Future help-seeking models need to capture the
      iterative referral process that many parents experience.

PMID- 17211718
TI  - Influence of oxide-based sintering additives on densification and mechanical
      behavior of tricalcium phosphate (TCP).
AB  - In this research, we studied and analyzed the effects of four different oxide
      based sintering additives on densification, mechanical behavior, biodegradation
      and biocompatibility of tricalcium phosphate (TCP) bioceramics. Selective
      sintering additives were introduced into pure TCP ceramics, in small quantities,
      through homogeneous mixing, using a mortar and pestle. The consequent powders of
      different compositions were pressed into cylindrical compacts, uniaxially and
      sintered at elevated temperatures, 1150 degrees C and 1250 degrees C, separately
      in a muffle furnace. X-ray powder diffraction technique was used to analyze the
      phase-purity of TCP after sintering. Hardness of these sintered specimens was
      evaluated using a Vickers hardness tester. Sintered cylindrical samples were
      tested under uniaxial compressive loading, as a function of composition to
      determine their failure strength. Biodegradation studies conducted using
      simulated body fluid under dynamic environment, revealed that these additives
      could control the rate of resorption and hardness degradation of TCP ceramics.

PMID- 17211719
TI  - Preparation of amino-functionalized mesostructured cellular foams and application
      as hosts for large biomolecules.
AB  - Large mesopores cellular foam (LMCFs) materials were synthesized using
      microemulsion templating in acidic solutions. The amine functional groups were
      attached to channels of LMCFs materials via post-synthesis grafting. The
      structural and chemical properties of these prepared materials were characterized
      by TEM, XRD, FTIR and nitrogen adsorption. These resulting materials had
      disordered mesopores with well-defined large mesopore. The bovine serum albumin
      (BSA) and glucose oxidase (GOx) were used for adsorption experiment. The
      biomolecule was immobilized by covalently couple to the interior surface of amino
      functionalized mesostructured cellular foams (AF-MCFs). The results showed that
      AF-MCFs had high-capacity bioimmobilization ability.

PMID- 17211720
TI  - A novel bioactive porous bredigite (Ca7MgSi4O16) scaffold with biomimetic apatite
      layer for bone tissue engineering.
AB  - The aim of this study was to develop a novel bioactive, degradable and
      cytocompatible bredigite (Ca(7)MgSi(4)O(16)) scaffold with biomimetic apatite
      layer for bone tissue engineering. Porous bredigite scaffolds were prepared using
      polymer sponge method. The bredigite scaffolds with biomimetic apatite layer
      (BTAP) were obtained by soaking bredigite scaffolds in simulated body fluid (SBF)
      for 10 days. The porosity and in vitro degradability of BTAP scaffolds were
      investigated. In addition, osteoblast-like cell morphology, proliferation and
      differentiation on BTAP scaffolds were evaluated and compared with beta
      tricalcium phosphate (beta-TCP) scaffolds. The results showed that BTAP scaffolds
      possessed 90% of porosity. The degradation of BTAP scaffolds was comparable to
      that of beta-TCP scaffolds. Cells on BTAP scaffolds spread well and presented a
      higher proliferation rate and differentiation level as compared with those on
      beta-TCP scaffolds. Our results indicated that BTAP scaffolds were degradable and
      possessed the function to enhance cell proliferation and differentiation, and
      might be used as bone tissue engineering materials.

PMID- 17211722
TI  - Growth and characterization of hydroxyapatite crystals by hydrothermal method.
AB  - Hydroxyapatite crystals were grown by hydrothermal method using dicalcium
      phosphate dihydrate crystals as a starting material. The grown crystals were
      found to be free from carbonate inclusion. Two distinct morphologies were
      obtained by following two different growth methods. Controlled slow growth
      process and rapid growth process results in hexagonal and whisker like
      morphologies.

PMID- 17211721
TI  - Electronic states spectroscopy of hydroxyapatite ceramics.
AB  - Photoluminescence, surface photovoltage spectroscopy and high-resolution
      characterization methods (Atomic Force Microscopy, Scanning Electron Microscopy,
      X-ray spectroscopy and DC conductivity) are applied to nanostructured
      Hydroxyapatite (HAp) bioceramics and allowed to study electron (hole) energy
      states spectra of the HAp and distinguish bulk and surface localized levels. The
      measured trap spectra show strong sensitivity to preliminary heat treatment of
      the ceramics. It is assumed that found deep electron (hole) charged states are
      responsible for high bioactivity of the HAp nanoceramics.

PMID- 17211723
TI  - The effect of acetaminophen on the crystal growth of calcium carbonate.
AB  - The effect of acetaminophen, a well known analgesic and fever-reducing medicine,
      on the calcium carbonate crystal growth was investigated under plethostatic
      conditions. The calcification rates measured was reduced by 9.1-63.2% in the
      presence of acetaminophen. Kinetic analysis according to a Langmuir-type
      adsorption isotherm lead to the calculation of an affinity constant K (aff) =
      8.33 x 10(2 )dm(3 )mol(-1). The apparent order found from kinetic data was two
      suggesting a surface diffusion controlled spiral growth mechanism.

PMID- 17211724
TI  - Titanium dioxide (TiO(2)) nanoparticles filled poly(D,L lactid acid) (PDLLA)
      matrix composites for bone tissue engineering.
AB  - Titanium dioxide (TiO(2)) nanoparticles were investigated for bone tissue
      engineering applications with regard to bioactivity and particle cytotoxicity.
      Composite films on the basis of poly(D,L lactid acid) (PDLLA) filled with 0, 5
      and 30 wt% TiO(2) nanoparticles were processed by solvent casting. Bioactivity,
      characterised by formation of hydroxyapatite (HA) on the materials surface, was
      investigated for both the free TiO(2) nanoparticles and PDLLA/TiO(2) composite
      films upon immersion in supersaturated simulated body fluid (1.5 SBF) for up to 3
      weeks. Non-stoichiometric HA nanocrystals (ns-HA) with an average diameter of 40
      nm were formed on the high content (30 wt% TiO(2)) composite films after 2 weeks
      of immersion in 1.5 SBF. For the pure PDLLA film and the low content composite
      films (5 wt% TiO(2)) trace amounts of ns-HA nanocrystals were apparent after 3
      weeks. The TiO(2) nanopowder alone showed no bioactivity. The effect of TiO(2)
      nanoparticles (0.5-10,000 microg/mL) on MG-63 osteoblast-like cell metabolic
      activity was assessed by the MTT assay. TiO(2) particle concentrations of up to
      100 microg/mL had no significant effect on MG-63 cell viability.

PMID- 17211726
TI  - Solute carrier family 11 member A1 gene polymorphisms in reactive arthritis.
AB  - To investigate the role of SLC 11A1 polymorphisms in the development of reactive
      arthritis, 91 patients with reactive arthritis and 163 healthy controls were
      enrolled in this study. The SLC 11A1 polymorphisms were determined by the method
      of polymerase chain reaction/restriction fragment length polymorphism. The
      genotype distributions of SLC 11A1 274, 823, 1703, and 1729+ 55 del 4 were
      significantly different between the patients with reactive arthritis and
      controls. The genotype frequency of SLC 11A1 274C/C was significantly decreased
      in the patients with reactive arthritis when compared with that of the controls.
      In contrast, the SLC 11A1 274C/T showed a significant association with reactive
      arthritis. The patients with reactive arthritis have a significantly higher
      frequency of SLC 11A1 823C/C than the controls. However, SLC 11A1 823T/T was
      resistant to the development of reactive arthritis. The allele frequencies of SLC
      11A1 274T and 823C were significantly increased in the patients with reactive
      arthritis in comparison with those of the controls, independent of HLA-B27. On
      the contrary, the allele frequencies of SLC 11A1 274C and 823T were significantly
      decreased in the patients with reactive arthritis. The estimated haplotype
      frequency of SLC 11A1 274C 823T 1703G 1729+55del 4 TGTG+ was significantly
      decreased in the patients with reactive arthritis when compared with that of the
      controls. In contrast, the estimated haplotype frequency of SLC 11A1 274T 823C
      1703G 1729+55 del 4 TGTG+ was significantly increased in the patients with
      reactive arthritis. This study shows that the SLC 11A1 274T and 823C alleles are
      associated with susceptibility to reactive arthritis independently of HLA-B27 in
      Taiwan. The SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ haplotype is associated
      with the development of reactive arthritis in Taiwan. In contrast, the SLC 11A1
      274C 823T 1703G 1729+55 del 4 TGTG+ haplotype may be a protective factor.

PMID- 17211725
TI  - "Spicing up" of the immune system by curcumin.
AB  - Curcumin (diferuloylmethane) is an orange-yellow component of turmeric (Curcuma
      longa), a spice often found in curry powder. Traditionally known for its an
      antiinflammatory effects, curcumin has been shown in the last two decades to be a
      potent immunomodulatory agent that can modulate the activation of T cells, B
      cells, macrophages, neutrophils, natural killer cells, and dendritic cells.
      Curcumin can also downregulate the expression of various proinflammatory
      cytokines including TNF, IL-1, IL-2, IL-6, IL-8, IL-12, and chemokines, most
      likely through inactivation of the transcription factor NF-kappaB. Interestingly,
      however, curcumin at low doses can also enhance antibody responses. This suggests
      that curcumin's reported beneficial effects in arthritis, allergy, asthma,
      atherosclerosis, heart disease, Alzheimer's disease, diabetes, and cancer might
      be due in part to its ability to modulate the immune system. Together, these
      findings warrant further consideration of curcumin as a therapy for immune
      disorders.

PMID- 17211727
TI  - Academic pathways between attention problems and depressive symptoms among urban
      African American children.
AB  - The present study investigated the pathways between attention problems and
      depressive symptoms, particularly the role of academic incompetence, among a
      community sample of urban African American children. Results supported the
      hypothesized path models from inattention to depressive symptoms for girls and
      boys. Academic performance in the spring of first grade mediated the relationship
      between inattention in fall of first grade and depressive symptoms in spring of
      3rd grade. The effects held when controlling for conduct problems and academic
      competence in first grade suggesting the path was specific to attention problems
      rather than a more general externalizing or school readiness pathway.
      Implications for designing interventions and prevention strategies for children
      with attention problems and depressive symptoms are discussed.

PMID- 17211728
TI  - A prospective case series of high-risk infants who developed autism.
AB  - The present paper documents the development of autism/autistic spectrum disorder
      in a consecutive series of nine high-risk infants followed prospectively from 6
      months of age. Evidence is provided for two broadly defined subgroups: the first
      subgroup (n = 6) showed a decrease in IQ between 12 and 24 or 36 months (from
      average/near average to severe cognitive impairment), whereas the second subgroup
      (n = 3) continued to obtain average or near average IQs. Signs of autism emerged
      and/or were more striking earlier in the first subgroup. In all nine children,
      early impairment in social-communicative development coexisted with atypical
      sensory and/or motor behaviors, as did a temperamental profile marked by
      irritability/distress and dysregulated state. Discussion focuses on issues raised
      by the pattern of findings.

PMID- 17211730
TI  - L1 expression as a marker for poor prognosis, tumor progression, and short
      survival in patients with colorectal cancer.
AB  - BACKGROUND: L1, a new target gene for Wnt/beta-catenin-TCF signaling, has been
      identified in the invasive front of colorectal cancer cells in vitro study. The
      L1 molecule is localized on the cell surface in tumor tissues, accompanied with
      loss of beta-catenin and E-cadherin. However, such association between L1
      expression and prognosis of colorectal cancer has not yet been investigated in
      clinical study. We investigated the expression of L1, E-cadherin, and beta
      catenin in tumor cells to determine correlations between the clinicopathologic
      characteristics and the expression of these molecules and to evaluate the
      efficacy of the use of these molecules as prognostic markers for patient
      survival. METHODS: We investigated 138 patients who received diagnoses of
      colorectal cancer and who underwent surgery between January 1995 and December
      2000 at the Korea University Hospital. Tissues were obtained from paraffin
      embedded blocks of the tumors and studied by tissue microarray analysis.
      Immunohistochemical staining for L1, beta-catenin, and E-cadherin was performed
      for each specimen. RESULTS: L1 expression was found to be correlated with
      advanced cancer stage (P = .001), distant metastasis (P < .001), and tumor
      recurrence (P = .006). Survival analysis showed that reduced expression of beta
      catenin and E-cadherin, and expression of L1 were statistically significantly
      related to poor survival. Multivariate analysis revealed that L1 expression was
      an independent prognostic factor for patient survival. CONCLUSIONS: L1 expression
      is associated with tumor progression and poor survival in patients with
      colorectal cancer and may be clinically useful as a marker for poor prognosis.

PMID- 17211729
TI  - Iloprost-containing liposomes for aerosol application in pulmonary arterial
      hypertension: formulation aspects and stability.
AB  - PURPOSE: Pulmonary arterial hypertension (PAH) is a severe and progressive
      disease. The prostacyclin analogue iloprost is effective against PAH, but
      requires six to nine inhalations per day. The feasibility of liposomes to provide
      a sustained release formulation to reduce inhalation frequency is evaluated from
      a technological point of view. METHODS: Liposomal formulations consisting of di
      palmitoyl-phosphatidyl-choline (DPPC), cholesterol (CH) and polyethyleneglycol-di
      palmitoyl-phosphatidyl-ethanolamine (DPPE-PEG) were prepared. Their physico
      chemical properties were investigated using dynamic light scattering, atomic
      force microscopy and differential scanning calorimetry. Stability of liposomes
      during aerosolization using three different nebulizers (air-jet, ultrasonic and
      vibrating mesh) was investigated with respect to drug loading and liposome size,
      pre- and post-nebulization. RESULTS: The phospholipid composition affected the
      diameters of liposomes only slightly in the range of 200-400 nm. The highest
      iloprost loading (12 microg/ml) and sufficient liposome stability (70% drug
      encapsulation post-nebulization) was observed for the DPPC/CH (70:30 molar ratio)
      liposomes. The formulation's stability was confirmed by the relatively high phase
      transition temperature (53 degrees C) and unchanged particle sizes. The
      incorporation of DPPE-PEG in the liposomes (DPPC/CH/DPPE-PEG, 50:45:5 molar
      ratio) resulted in decreased stability (20-50% drug encapsulation post
      nebulization) and a phase transition temperature of 35 degrees C. The vibrating
      mesh nebulizer offered a number of significant advantages over the other
      nebulizers, including the production of small aerosol droplets, high output, and
      the lowest deleterious physical influence upon all investigated liposomes.
      CONCLUSION: Iloprost-loaded liposomes containing DPPC and CH components yield
      formulations which are well suited to aerosolization by the vibrating mesh
      nebulizer. The investigation of sustained release effects for the treatment of
      PAH in ex vivo and in vivo models is under way.

PMID- 17211732
TI  - Emergency room presentation of colorectal cancer: a consecutive cohort study.
AB  - BACKGROUND: Emergency room presentation (ERP) in colorectal cancer (CRC) is
      associated with worse cancer-related outcomes. The goal of this study was to
      determine the frequency of ERP and identify factors associated with ERP of CRC.
      METHODS: We performed a prospective consecutive cohort study of all patients
      undergoing resection for CRC from 02/2002 to 02/2004. Standardized data
      collection involved hospital record review, patient interview, and prospective
      follow-up. ERP was defined as the diagnosis and/or surgical treatment of CRC as a
      result of presentation to the emergency department. RESULTS: Of the 455 patients
      in the study 108 (24%) had ERP. Presentation of those with ERP was obstruction in
      46 (43%), bleeding/anemia in 35 (32%), pain in 25 (23%), and other (2%). The ERP
      cohort was older (mean age 70.8 vs. 67.0 years, P = 0.005). ERP was more common
      amongst females (29.7 vs. 18.2%, P = 0.004) and obesity appears to be associated
      with increased rates of ERP. ERP of CRC was associated with more advanced TNM
      stage. The ERP cohort had longer length of stay in hospital (median 10 vs. 8 days
      respectively, P < 0.001). Peri-operative mortality was higher in ERP patients
      (7.4 vs. 2.3%, P = 0.03). CONCLUSIONS: ERP in CRC was not infrequent and appeared
      to be associated with female gender and weight. The known negative prognostic
      impact of ERP, combined with the increased peri-operative mortality and length of
      stay, would suggest a potential benefit to targeted strategies aimed at reducing
      the use of the emergency room in the diagnosis and treatment of CRC.

PMID- 17211731
TI  - Treatment of pathological humeral shaft fractures with unreamed humeral nail.
AB  - PURPOSE: The purpose of this study is to analyze the results of intramedullary
      fixation of pathological humeral shaft fractures using an unreamed humeral nail
      (UHN). PATIENTS & METHODS: Twenty-one consecutive patients with 24 humeri
      fractured secondary to metastatic disease were retrospectively reviewed. The
      primary tumors included carcinomas of breast (11), kidney (2), multiple myeloma
      (2), colon (2), prostate (1), thyroid (1), lymphoma (1) and unknown origin (1).
      All fractures were stabilized with antegrade unreamed humeral nailing. Cemented
      technique was performed in 5 procedures. The mean age was 64 (range, 40-86), male
      to female ratio 6:15. RESULTS: Blood loss was unremarkable in 19 patients (22
      procedures). Two patients who underwent fixation of additional pathological
      fractures during the same operation were given a total of 3 units of PC
      perioperatively. Mean postoperative hospitalization period due to one UHN
      procedure alone was 3 days (range, 2-7 days). Two patients died of their disease
      within 3 weeks of surgery. The remaining 19 patients returned to nearly normal
      function within 6 weeks after nailing. One patient developed postoperative local
      wound cellulitis. Relief of pain was rated as good in all but one patient.
      Adjuvant therapy was given in 20 procedures. Bony union was achieved in 88%
      (15/17) of all the cases where the patient had survived a minimum of 3 months.
      CONCLUSION: Unreamed humeral nailing of the pathological humeral shaft fractures
      provides immediate stability and pain relief, minimum morbidity and early return
      of function to the extremity.

PMID- 17211733
TI  - Comparative analysis of predictive biomarkers for therapeutical strategies in
      colorectal cancer.
AB  - BACKGROUND: Prognostic information regarding the risk of postoperative tumor
      recurrence defined by a profile of serological, morphological and/or molecular
      markers can have potential value, particularly for patients with colorectal
      carcinoma (CRC) of the International Union Against Cancer (UICC) stage II/III who
      may benefit from adjuvant chemotherapy after surgery. METHODS: A retrospective
      study of 783 patients with CRC (UICC I-III) including a subgroup analysis of 116
      subjects was conducted to determine preoperative serum carcinoembryonic antigen
      (CEA), carbohydrate antigen (CA) 19-9, and p53 serum levels. In addition, protein
      and gene expression of p53, CEA, and adenomatous polyposis coli (APC) was
      assessed in the tumors of those patients. The values of all serological,
      morphological, and molecular parameters were correlated with clinicopathological
      characteristics for their predictive value of tumor recurrence over a mean follow
      up period of 32 +/- 6.2 months. RESULTS: Serum CEA but not CA 19-9 or p53 was a
      significant prognostic factor for disease-free survival, along with UICC and T/N
      stage. When comparing elevated CEA, CA 19-9, and p53 serum levels with expression
      of the markers in the tumors, their overall expression was found to be 61.3% in
      the serum versus 93.5% in the tumor in analyzed patients (n = 116). In
      particular, all patients in UICC stages I-III who demonstrated at least three
      elevated markers (CEA/CA 19-9/p53) in serum and/or in the tumor presented with
      tumor recurrence/metastases. CONCLUSION: Overall increased p53, CEA, and CA 19-9
      serum levels and their marker expression in the tumor may be used at the time of
      primary tumor removal for defining patients at risk for tumor recurrence.

PMID- 17211734
TI  - A multidimensional multispecies continuum model for heterogeneous biofilm
      development.
AB  - We propose a multidimensional continuum model for heterogeneous growth of biofilm
      systems with multiple species and multiple substrates. The new model provides a
      deterministic framework for the study of the interactions between several
      spe1cies and their effects on biofilm heterogeneity. It consists of a system of
      partial differential equations derived on the basis of conservation laws and
      reaction kinetics. The derivation and key assumptions are presented. The
      assumptions used are a combination of those used in the established one
      dimensional model, due to Wanner and Gujer, and for the viscous fluid model, of
      Dockery and Klapper. The work of Wanner and Gujer in particular has been
      extensively used through the years, and thus this new model is an extension to
      several spatial dimensions of an already proven working model. The model
      equations are solved using numerical techniques, for purposes of simulation and
      verification. The new model is applied to two different biofilm systems in
      several spatial dimensions, one of which is equivalent to a system originally
      studied by Wanner and Gujer. Dimensionless formulations for these two systems are
      given, and numerical simulation results with varying initial conditions are
      presented.

PMID- 17211735
TI  - Estimation and prediction with HIV-treatment interruption data.
AB  - We consider longitudinal clinical data for HIV patients undergoing treatment
      interruptions. We use a nonlinear dynamical mathematical model in attempts to fit
      individual patient data. A statistically-based censored data method is combined
      with inverse problem techniques to estimate dynamic parameters. The predictive
      capabilities of this approach are demonstrated by comparing simulations based on
      estimation of parameters using only half of the longitudinal observations to the
      full longitudinal data sets.

PMID- 17211742
TI  - [Sexual medicine].

PMID- 17211744
TI  - [Report of the Robert-Koch-Institute regarding the addition of (certain) cleaning
      and disinfection devices to the list of tested and approved disinfection
      disinfection materials and devices according to 18 IfSG].

PMID- 17211745
TI  - [Classification of substances hazardous to water].

PMID- 17211748
TI  - Long-term hemodynamic benefit of biventricular pacing depending on coronary sinus
      lead position.
AB  - BACKGROUND: Acute studies in cardiac resynchronization therapy (CRT) showed that
      hemodynamic effects may depend on the coronary sinus (CS) lead position. However,
      there are no data on the longterm effect of CS lead position. METHODS: In 45
      heart failure patients with left bundle branch block and QRS >150 ms (age 59+/-10
      years, 17 dilative cardiomyopathy, 23 ischemic, 5 valvular), biventricular
      pacemakers were implanted. CS leads were positioned in posterior (P, n=15),
      lateral (L, n=19) or, if no other option available, anterior (A, n=11) side
      branches. Before and 6 months after implantation, clinical state,
      echocardiography, brain natriuretic peptide (BNP) and right heart catheterization
      were evaluated. RESULTS: Baseline parameters were similar between groups. After 6
      months, there were 32/34 responders in groups P and L compared to 7/11 responders
      in group A (94 vs groups P and L: Arterial pressure +8 and +9% vs +2%; PCWP -23
      and -15% vs -4%, pulmonary pressure -18 and -12% vs -3% (p<0.01 for A vs P+L);
      cardiac index +21 and +12% vs +11% (p=0.03 for A vs P). BNP was reduced by 55,
      35, and 27% (p=0.05 for A vs P). Ejection fraction increased in P and L by 40 and
      41%, respectively, but only by +19% in A (p<0.03 for A vs P+L). CONCLUSION:
      Chronic CRT improves ejection fraction, BNP and hemodynamic measurements
      predominantly in patients with lateral and posterior CS lead positions. Anterior
      lead positions should be avoided.

PMID- 17211749
TI  - [Telemedical monitoring of electrocardiograms after cardiac surgery--results from
      a pilot study among 208 patients].
AB  - BACKGROUND: An increasing number of older patients undergo cardiac surgery.
      Complications after cardiac surgery such as rhythm disorders, myocardial
      infarction and atypical symptoms frequently lead to ambulatory visits and
      hospitalisations. Telemonitoring might be one method for rapid and efficient
      detection and classification of symptoms. We examined in this pilot study if ECG
      telemonitoring after cardiac surgery proves to be an useful, reliable and
      accepted procedure with respect to cost and risk reduction. METHODS & RESULTS:
      Two hundred eight patients (46 female, 162 male) received after surgery an
      individually adjusted portable 12-lead ECG-monitor. Within three months all
      incoming ECG-recordings were analysed. In total, 1387 calls from 165 patients
      (80% use) with ECG-recording (8,4 calls per patient) were collected. There were
      235 calls (17%) because of symptoms, 51% of them were registered between 6 PM and
      8 AM. Fourteen (6%) out of those 235 emergency calls with ECG-registration led to
      hospitalisation (n=5) or ambulatory visits next day. The remaining 221 ECG showed
      no pathological ECG-signs and the patients could be managed with telephonic
      advice, reassurance and telemedical follow up. Readmissions were due to angina
      pectoris, severe but unspecific chest pain and cardiac decompensation (n=3) as
      well as rhythm disturbances (n=2). Almost 75% of all emergency calls were
      recorded within the first 60 min after the onset of symptoms. CONCLUSION: Older
      patients reproducibly are able to telemetrically transmit electrocardiograms
      after a short training before discharged home. Although there is a low incidence
      of complications among our study population, telemedical ECG-monitoring rapidly
      helps to differentiate between the symptoms leading to increased patient safety
      and prevented further damage. The reduction of ambulatory visits and
      hospitalisations only for treatment of objectified symptoms may lead to a overall
      cost reduction in the health care system. The reduction of unnecessary
      hospitalisations and ambulatory visits might also contribute to an optimised time
      management.

PMID- 17211750
TI  - [Sports medical aspects in cardiac risk stratification--heart rate variability
      and exercise capacity].
AB  - The present study investigates the association of the predicted CHD-risk (PROCAM)
      with the individual endurance capacity and heart rate variability (HRV) in a
      population-based sample of sedentary elderly. After stratification, in 57 men
      (48.1+/-9.5 yrs.) with an overall PROCAM-risk <10% (28.7+/-10.9 points) and 22
      men (54.5+/-7.7 yrs.) with a coronary 10-year risk > or =10% (50.8+/-5.6 points)
      cycle ergometries and short-term HRV analysis of time (RRMEAN, SDNN, RMSSD) and
      frequency domain parameters (LF, HF, TP, LF/HF) were conducted. Additionally the
      autonomic stress index (SI) was calculated. Nonparametric tests were used for
      statistical correlation analysis (Spearman rho) and group comparisons (Mann
      Whitney). For endurance capacity [W/kg] (r=-0.469, p<0.001), SDNN (r=-0.302,
      p<0.05), RMSSD (r= -0.311, p<0.05), LF (r=-0.325, p<0.05), HF (r= -0.311, p<0.05)
      and TP (r= -0.307, p<0.05) negative monotone correlations with the coronary score
      risk were determined. Significant positive correlations were calculated for SI
      (r=0.476, p<0.001). Except for RRMEAN and LF/HF significant group differences
      (p<0.05) were computed for SDNN (30.0+/-20.0 vs 20.0+/-10.0 ms), RMSSD (22.2+/
      18.3 vs 18.0+/-8.7 ms), LF (90.9+/-241.5 vs 41.35+/-81.1 ms(2)), HF (43.0+/-105.1
      vs 18.0+/-27.0 ms(2)) and TP (189.0+/-457.1 vs 100.0+/-157.6 ms(2)). Significant
      differences (p<0.01) were evaluated for exercise capacity (2.4+/-0.5 vs 1.8+/-0.3
      W/kg) and SI (90+/-183 vs 322+/-291). The results underline the predictive value
      of HRV analysis in risk stratification and outline the interrelation of a
      decreased exercise capacity and autonomic function with a raised individual 10
      year cardiac risk. As an independent parameter of the vegetative regulatory state
      the stress index may contribute to an increased practical relevance of short-time
      HRV analysis.

PMID- 17211751
TI  - Long and short QT syndrome.
AB  - In the past decade molecular genetic analysis has greatly expanded our knowledge
      about inherited arrhythmogenic syndromes. The congenital long QT syndrome (LQTS)
      and the recently described short QT syndrome (SQTS), with the defining
      characteristic of abnormal prolongation or shortening of the QTc interval on the
      surface electrocardiogram, are caused by cardiac ion channel dysfunctions. These
      "channelopathies" show a high degree of genetic heterogeneity of the molecular
      pathways in terms of the relationships between genetic defects and phenotypic
      expression. In this brief review we summarize the current understanding of the
      molecular basis of long and short QT syndrome with focus on the impact of
      molecular genetics on the clinical management of these diseases.

PMID- 17211752
TI  - [Coronary artery disease--relevance of total coronary revascularization on the
      incidence of malignant arrhythmias].
AB  - Myocardial ischemia induces redistribution of different ions (H(+), K(+), Na(+),
      Ca(++)) across the cardiomyocyte membrane, as well as the loss of intracellular
      ATP content. This results in changes in the electrical properties including
      shortening of the action potential, appearance of delayed afterpotentials, and a
      modified refractoriness of the cardiomyocyte. These changes may induce or support
      malignant cardiac arrhythmias. Supersensitivity of sympathetic denervated
      myocardium may further support the electrical instability of ischemic
      myocardium.Virtues of studies indicate that patients with coronary artery disease
      who develop complex arrhythmias during or after exercise bear a substantially
      increased risk for sudden cardiac death. Other studies report about arrhythmic
      stabilization and reduced mortality if patients with reversible myocardial
      ischemia receive complete revascularization. However, none of these studies is
      without methodological flaws. Due to the lack of methodologically sound studies
      in sufficiently large patient cohorts, the question whether complete coronary
      revascularisation improves the prognosis of patients with coronary artery disease
      and which strategy (medical, interventional, or surgical) warrants the best
      outcomes remains open.

PMID- 17211753
TI  - [Arterial hypertension, left ventricular hypertrophy, and ventricular
      arrhythmias].
AB  - Patients with hypertensive heart disease have frequently ventricular arrhythmias
      in the 24-h-holter-EKG. Those patients with severe forms of arterial hypertension
      have more high grade ventricular tachycardia than those with less severe
      hypertension. Sudden cardiac death in arterial hypertensive seems to be linked
      with the prevalence of coronary artery disease, whereas LV hypertrophy is only a
      co-factor.

PMID- 17211754
TI  - Inadvertent malposition of a transvenous pacing lead in the left ventricle.
AB  - We report the case of inadvertent malpositioning of a pacemaker lead in the left
      ventricle. The lead went through an open foramen ovale from the right to the left
      atrium and through the mitral valve into the left ventricle. After a review of
      the literature, we decided to anticoagulate the patient and leave the electrode
      in place. During a follow-up period of 16 months, there were no clinical
      complications.

PMID- 17211755
TI  - Use of telemedicine in the diagnosis of paroxysmal atrial fibrillation and to
      monitor the effect of antiarrhythmic drug therapy.
AB  - We present the case of a patient with highly symptomatic tachyarrhythmias for 2
      years without any arrhythmia documentation despite numerous ECG and Holter
      registrations. By means of telemedicine, it was possible to document the
      arrhythmia--in this case atrial fibrillation--within 10 days and to start
      antiarrhythmic drug treatment with flecainide and metoprolol. This case
      demonstrates the diagnostic potential of telemedicine in patients with recurrent
      episodes of tachyarrhythmias in whom episodes are not sufficiently frequent to
      allow diagnosis by Holter monitoring. Telemedicine may also be advantageous for
      ECG monitoring during the early phase after cardioversion or initiation of
      specific antiarrhythmic pharmacotherapy in order to detect potential drug-induced
      proarrhythmic changes.

PMID- 17211757
TI  - [Cardiac resynchronization therapy in patients with permanent atrial fibrillation
      -with or without atrial lead?].
AB  - A 59-year-old patient received a biventricular defibrillator for cardiac
      resynchronization therapy (CRT) due to severe heart failure and a left bundle
      branch block. He had suffered from mitral stenosis and had received valve
      replacement 16 years earlier. Because he had permanent atrial fibrillation since
      that time, no atrial lead was implanted. His symptoms improved with CRT until he
      received adequate shock therapy for a rapid ventricular tachyarrhythmia. After
      that his symptoms deteriorated again severely. The ECG recorded during an
      unscheduled follow-up visit 1 week after the shock explains the reason.

PMID- 17211758
TI  - [4. Apropos of postpacing interval].

PMID- 17211764
TI  - [Pharmacoeconomic analyses--chance or 4th hurdle for innovative drugs].
AB  - The reimbursement process for pharmaceuticals is increasingly confronted with
      what is often called "the fourth hurdle". This criterion is required even when
      therapeutic efficacy, safety and quality have been controlled for. Such a fourth
      hurdle has also been introduced in Austria in 2002 for the reimbursement of
      innovative drugs. Despite resistance, it can also be seen as a chance for
      innovative medicines. By implementing cost/effectiveness analyses it is possible
      to give a quantitative account of cost/effectiveness advantages. It is however
      questionable to advocate this procedure in connection with imposing a limiting
      peak-price.

PMID- 17211765
TI  - [Relevance of pharmacoeconomic analyses to price and reimbursement decisions in
      Austria].
AB  - Since the social sick funds have only limited amounts of money at their disposal,
      whereas the pharmaceutical market is constantly growing, thorough evaluations
      have to be undertaken how contributions are to be spent to get adequate value for
      money and especially to gain utmost benefit for the patients. When deciding on
      whether a pharmaceutical is listed in the Code of Reimbursement or not,
      pharmacoeconomic studies are obligatory in two cases: for real innovations with
      substantial therapeutic benefit and for applications for inclusion in the Yellow
      Box, when there are no alternatives listed in the Yellow Box. On the basis of the
      pharmacoeconomic study a comprehensible and justifiable cost/use relation of the
      pharmaceutical applied for should be proven in comparison with therapeutic
      alternatives in Austria. However, a pharmacoeconomic study is always only one
      aspect among others deciding on reimbursement and price. Even though the
      pharmaceutical applied for is not included in the Code of Reimbursement,
      reimbursement is possible in special cases if there is no adequate pharmaceutical
      listed in the Code of Reimbursement and the pharmaceutical is absolutely needed
      for therapeutic reasons. In these cases prior approval from a chief medical
      officer is required. Pharmacoeconomic studies for the purpose of section sign 25
      of the Rules of Procedure for publishing the Code of Reimbursement (VO-EKO) must
      meet the following requirements: From a methodical point of view both cost
      effectiveness analyses and--in justified cases--cost-utility analyses may be
      used. Due to required accuracy and traceability incremental analyses are
      preferred. Medical and economic data underlying the pharmacoeconomic study have
      to show a high degree of validity and evidence. The perspective to be taken is
      that of the Austrian Health Insurance. When determining the therapeutic
      alternatives, the most frequent indication, the most purposeful medical dosage
      and the main group of affected patients have to be considered. Hereby the order
      "Green Box-Yellow Box-Red Box" has to be taken into account. The direct costs of
      the obligatory benefits of the social insurance institutions of medical treatment
      (medical assistance, drugs, substitute assistance), institutional care (based on
      LKF points) and the medical measures of rehabilitation are to be set. Due to
      required transparency and traceability quantity and cost structure have to be
      listed separately. Prices of single items and resource usage in form of units of
      measurement have to be stated. Studies performed in other countries than Austria
      may be subject to different health care systems, general conditions, therapeutic
      alternatives and costs and have therefore to be adapted to Austrian conditions.
      It must not be disregarded that pharmacoeconomics as any other science comprises
      different opinions and basic approaches and that pharmacoeconomics is making
      progress all the time. However, considering their limitations with regard to the
      interpretation of the results, pharmacoeconomic studies are a key factor for
      assessing new pharmaceuticals and represent an important contribution to
      reimbursement and price decisions in Austria.

PMID- 17211766
TI  - [Limitations of pharmacoeconomics from a clinical-pharmacological point of view].
AB  - Pricing decisions for pharmaceuticals usually follow a two-step process. A final
      economic evaluation needs to be based on a prior clinical-pharmacological
      evaluation of a new drug in light of therapeutic alternatives. However, major
      limitations for this evaluation process may be encountered. Most notably a lack
      of (1) evidence-based data, (2) clinical endpoint data, (3) direct comparator
      studies or (4) an impaired "assay sensitivity" may cause uncertainty about the
      appropriate value of a new drug. Moreover situations with (5) incremental, small
      benefit, (6) lack of precedents in case of innovations or (7) obvious "efficacy
      effectiveness gaps" may pose challenges in the pricing decision process for
      pharmaceuticals.

PMID- 17211767
TI  - [Theoretical implications of health economic evaluations in an Austrian context].
AB  - It is a well acknowledged fact that steep increases in health expenditures are
      mainly due to improvements in health technologies as well as the ageing of
      population combined with mounting societal preferences towards health. This
      "natural" tendency increasingly faces constraints of public budgets. Therefore,
      both efficiency and effectiveness considerations have to be put in place in order
      to allocate financial resources in such a way as to foster optimal results. This
      can best be done by implementing the analytical tool of health economic
      evaluations. However, in the Austrian context health economic evaluations only
      play a minor role as yet. The major hindrance for this unsatisfactory situation
      is the complex system of health finance which impedes overall considerations
      beyond the array of particular budgets.

PMID- 17211768
TI  - [Guidelines for health-economic evaluations in Austria].
AB  - BACKGROUND: The evaluative health economics is a recent field of research in
      health economics. Cost-effectiveness decisions play an increasing role,
      particularly for policy-makers to find systematic decisions under uncertainty.
      The task is all the more important as the use of innovative health technologies
      for diagnosis, prevention and treatment is rapidly expanding and thus leads to
      financial restrictions in health care. Hence, decision making has to be supported
      by systematically implementing analytical tools. METHODS: When it comes to
      interpret the results of health-economic evaluations in a valid way it is
      necessary that state-of-the-art methodology is carried out in a transparent way.
      It is in this vein that guidelines were developed for Austria. On the one hand,
      they should set standards but, on the other hand, they should not restrict
      methodical progress guided by freedom of scientific research in health economics.
      CONCLUSIONS: Setting guidelines of health-economic evaluations is an important
      breakthrough in Austria.

PMID- 17211769
TI  - [A complex process: decision-making in general practice: 117 structured case
      analyses].
AB  - BACKGROUND: A variety of factors seem to play a role in decision-making in
      general practice. To describe the complexity of this process a vague symptom with
      a broad spectrum of possible causes and outcomes was chosen: dizziness. Aim of
      this study was to provide a conceptual framework to describe and assess the
      complex reasoning process of general practitioners. METHODS: 22 GPs were
      interviewed about the patients seeking help for dizziness. The semi-structured
      focussed interviews were qualitatively analysed by consensus method. RESULTS: By
      117 structured case analyses factors with influence on the decision-making
      process were identified and assigned to 7 different domains. Concepts described
      in literature were found as well as less well-known or even not accepted motives.
      CONCLUSIONS: Influenced by a variety of parameters, the decision-making process
      in general practice is complex. It is necessary to be aware of them to be able to
      deal with them.

PMID- 17211773
TI  - [Narcissism--variable of personality and personality disorder].
AB  - OBJECTIVE: This review provides information about the current state of knowledge
      concerning narcissism. METHODS: Viewing narcissism as a psychological construct,
      a dimension of personality and as a psychiatric disease, presenting of models
      about development and treatment of narcissistic tendencies or of narcissistic
      personality disorder (NPD). Statements about phenomenology, diagnosis, and
      classification, comorbidity, epidemiology, pharmacological treatment and current
      psychotherapy, and prognosis of NPD are presented. RESULTS/DISCUSSION: There are
      three main aspects of narcissism: 1. narcissism as a psychological construct in
      the sense of personality variable, 2. as a personality accentuation as a factor
      of vulnerability for other psychological disorders and 3. narcissism as a
      personality disorder in the sense of a psychiatric disease (NPD). There are no
      clear boundaries between these forms of narcissism. The NPD is recognized as a
      personality disorder by DSM-IV but not by ICD-10. There is a clear lack of
      scientific studies on the neurobiology, psychology and psychotherapeutic as well
      as psychopharmacological treatment.

PMID- 17211770
TI  - [Clinical features, diagnosis and treatment of HIV-induced neuropsychiatric
      disorders].
AB  - Since the acquired immune deficiency syndrome (AIDS) was first recognized in
      1981, more than 25 million individuals have died from complications of the human
      immunodeficiency virus (HIV) infection. The introduction of highly active
      antiretroviral therapy (HAART) in 1995 has resulted in a significantly decreased
      incidence rate of AIDS in the developed world. As HAART led to considerable
      improvements in survival for patients with HIV infection, HIV-neurotropically
      associated neuropsychiatric disorders have become an increasingly important
      challenge for clinical medicine. This article gives an overview of epidemiology,
      clinical features, diagnosis, and therapy of HIV-induced cognitive-motor
      impairments including HIV-associated dementia complex, organic mood disorders and
      psychosis.

PMID- 17211774
TI  - [Close relationships in childhood and adulthood from the viewpoint of structural
      analysis of social behavior (SASB) and attachment theory].
AB  - Two theoretical approaches to interpersonal experiences and behavior are
      empirically related to each other: Structural Analysis of Social Behavior (SASB)
      and attachment theory. The focus is on the most important relationships during
      life-span: relationships with mother and father in childhood, which were measured
      retrospectively, and romantic relationships in adulthood. 93 outpatients of a
      psychosomatic clinic took part in the study. Self-report measures were used to
      assess SASB-dimensions affiliation and autonomy and attachment variables (Intrex
      short form, Short measure of attachment to parents, Bochum Adult Attachment
      Questionnaire). Affiliation was strongly related to attachment to mother, father
      and romantic partner. Subjects classified as secure with respect to attachment to
      parents reported higher levels of affiliation than subjects classified as anxious
      or avoidant. Correspondingly, affiliation was negatively correlated with
      avoidance and anxiety in adult attachment to the romantic partner. On the other
      hand, autonomy was shown to be unrelated to attachment variables. Results
      indicate that the SASB-dimension affiliation and attachment security are closely
      associated.

PMID- 17211775
TI  - [Good preconditions for a cooperation between physicians and psychosocial
      professionals in prenatal diagnostic counselling--empirical results referring to
      the initial situation of a model project].
AB  - In a model project, the cooperation between physicians and psychosocial
      professionals is supported in order to improve the quality of counselling in
      prenatal diagnostics (PND). For this purpose, interprofessional quality circles
      (IQZ) had been established in six different places in Germany and were
      accompanied scientifically. By means of a questionnaire, data on self-perception
      and the perception of the respective other group, the cooperation practice and
      various attitudes in the context of PND had been collected. Sociodemographic
      characteristics of the participants and structural features of counselling had
      been described, characteristics of attitudes towards PND and of the therapeutic
      relationship had been examined by means of MANOVA or non-parametrically on the
      item level. The results show that notwithstanding a high willingness a
      cooperation between physicians and psychosocial professionals rarely takes place.
      Although the counselling offers of the two professional groups would complement
      each other, differences in the attitudes towards PND, most of all considering the
      relevance of medical pre-findings performing an invasive PND, depend on the
      gender of the professional. It is recommended to include these results into the
      future IQZs, and to stimulate the participants to consider the complementary
      attitude of the other professional/gender group in the interest of a common
      counselling concept.

PMID- 17211776
TI  - [Elevated costs of treatment in medical inpatients with psychiatric comorbidity
      are not reflected in the German DRG-system].
AB  - OBJECTIVE: So far, it remains unclear whether treatment of psychiatric
      comorbidity in medical inpatients is appropriately reflected in the German
      Diagnosis-Related Groups (DRG) system. Therefore, we investigated the
      relationship of psychiatric disorders and costs, returns, net gain, and duration
      of hospitalization in internal medicine inpatients. METHODS: For a period of 1
      year, we analyzed costs, net gain and other outcome variables according to the
      DRG system for all inpatients of a university department of internal and
      psychosomatic medicine (n = 697). Psychiatric disorders were diagnosed by the
      treating physicians based on clinical criteria and results from the Patient
      Health Questionnaire (PHQ). With respect to the outcome variables, we compared
      three groups of patients with none, one, and more than one psychiatric disorder
      controlling for sociodemographic characteristics. RESULTS: The average total
      costs of the hospitalization (M +/- SD) for internal medicine patients without
      psychiatric comorbidity (4357 +/- 5312 euro), for patients with one psychiatric
      disorder, (4733 +/- 5389 euro), and for patients with more than one psychiatric
      disorder (7163 +/- 8277 euro) differed significantly (p = 0.0003). However, the
      increased costs for patients with psychiatric comorbidity were not related to
      elevated returns: the net gain for patients without psychiatric comorbidity was
      457 +/- 2884 euro; in contrast, the treatment of internal medicine patients with
      one and more than one psychiatric disorder resulted in a net loss of - 260 +/-
      2389 euro and - 348 +/- 3370 euro, respectively (overall group difference, p =
      0.03). CONCLUSIONS: Additional work and expenses caused by patients with
      psychiatric comorbidity should be documented and reflected in the revenue
      systems. Practical self-report screening questionnaires may help to detect and
      treat psychiatric disorders in internal medicine inpatients as early as possible.

PMID- 17211779
TI  - [For and against: attention deficit syndrome (ADS)--a diagnosis that neither
      helps patients nor therapists].

PMID- 17211780
TI  - [Effects of aggression management trainings for mental health care and disability
      care staff--systematic review].
AB  - BACKGROUND: Aggression management trainings for staff have been implemented in
      many organizations of mental health care and disability care. The efficacy of
      such programmes has rarely been analysed. METHODS: A systematic review was
      conducted which contains all published evaluation studies on aggression
      management trainings. Inclusion criteria were before-and-after-comparisons or
      control group designs. RESULTS: 39 published studies were included. Study quality
      has to be regarded as low. Concerning the results of the studies, no clear trend
      emerged in direction of minimising violent incidents. However, studies revealed
      clear positive effects on knowledge about violence and on staff's confidence to
      cope with difficult situations. CONCLUSIONS: Sensitisation effects in staff after
      getting trained probably lead to reporting bias. Although the results on the
      number of violent incidents remain unclear, it is recommended to conduct
      comprehensive aggression management trainings in mental health and disability
      care institutions.

PMID- 17211782
TI  - Duhamel Lecture: the incurability of Hirschsprung's disease.

PMID- 17211783
TI  - Extracorporeal membrane oxygenation in infants with congenital diaphragmatic
      hernia: a systematic review of the evidence.
AB  - AIM: The aim of this study was to evaluate the evidence supporting the use of
      extracorporeal membrane oxygenation (ECMO) in infants with congenital
      diaphragmatic hernia (CDH) and severe respiratory failure. METHODS: Medline,
      Embase, ISI Current Contents and Biosis databases were searched using a defined
      strategy. Case reports and opinion articles were excluded. We performed: 1) a
      systematic review of non randomised studies comparing mortality when ECMO was not
      available with a period when ECMO was available. Mortality was classified as
      "early" (before hospital discharge) and "late" (after discharge). Patients were
      classified as "ECMO" and "non-ECMO" candidates according to criteria reported by
      the authors; 2) a meta-analysis of randomised controlled trials (RCTs) comparing
      ECMO and conventional mechanical ventilation (CMV). Differences in mortality are
      reported as relative risk (RR) and 95 % confidence intervals. RESULTS: A)
      SYSTEMATIC REVIEW: 658 studies and 21 (2043 patients) fulfilled the entry
      criteria. Both early (RR 0.60 [0.51-0.70]; p < 0.001) and late mortality (RR 0.63
      [0.53-0.73]; p < 0.001) were significantly lower when ECMO was available than
      when ECMO was unavailable. This difference in mortality was observed in "ECMO
      candidates" (RR 0.46 [0.32-0.68]; p < 0.001) but not in "non-ECMO candidates" (RR
      0.80 [0.58-1.10]; p = 0.17). B) META-ANALYSIS: 3 trials comparing ECMO and
      conventional ventilation were identified which included 39 infants with CDH. The
      early mortality was significantly lower with ECMO compared to CMV (RR 0.73 [95 %
      CI 0.55-0.99]; p < 0.04), however, late mortality was similar in the two groups
      (RR 0.83 [0.66-1.05]; p = 0.12). CONCLUSIONS: Non randomised studies suggest a
      reduction in mortality with ECMO. However, differences in the indications for
      ECMO and improvements in other treatment modalities may contribute to this
      reduction. The meta-analysis of RCTs indicates a reduction in early mortality
      with ECMO but no long-term benefit. A large RCT in infants with CDH and severe
      respiratory failure is warranted.

PMID- 17211784
TI  - The advantages and disadvantages of nerve monitoring during thyroid surgery in
      childhood.
AB  - BACKGROUND: Intraoperative damage of the recurrent laryngeal nerve (RLN) and the
      external branch of the superior laryngeal nerve (EBSLN) are common and cause
      complications in thyroid surgery. The method of intraoperative
      electrophysiological neuromonitoring (IONM) of the RLN and the EBSLN has been
      used in adults for several years. The question is whether IONM can be used in
      paediatric surgery for the identification and functional control of the RLN and
      the EBSLN, and what the advantages and disadvantages of using it are. METHODS:
      Surgical treatment of benign (n = 9) and malign (n = 2) thyroid diseases was
      carried out in eleven children (median age: 13 years) with a total of 18 nerves
      at risk (NAR). The function of the vocal cord was monitored in all children
      before and after surgery. Intraoperative identification and functional control of
      RLN and EBSLN was performed using the Neurosign 100. All results before and after
      resection of the thyroid gland were documented. RESULTS: A clear and reliable
      identification of the RLN and the EBSLN was possible in all cases. All NAR showed
      a constant physiological nerve signal before and after surgical resection of the
      thyroid gland. However, in one young patient the postoperative examination of the
      vocal cord revealed a partial paralysis on the left side after thyroidectomy,
      despite the constant intraoperative signal of the RLN. After a period of six
      months, normal functioning had resumed. CONCLUSION: The IONM of both RLN and
      EBSLN in adult surgery could be used successfully in paediatric surgery. In this
      study a clear and positive identification of both nerves was possible in all
      patients. Therefore the IONM of the RLN and EBSLN could develop into a successful
      and easy method for the prevention of intraoperative nerve damage during thyroid
      surgery in childhood and young adolescence. Assuming that a constant IONM signal
      represents a normal vocal cord, our evaluation showed that there is a small
      percentage of false negative and positive results.

PMID- 17211785
TI  - "Total Gastric Dissociation (TGD)" in difficult clinical situations.
AB  - BACKGROUND: Since the first report by Bianchi in 1997, TOGD has been found to be
      safe and effective in patients with gastro-oesophageal reflux (GOR) with
      neurological impairment. This paper explores the versatility of total gastric
      dissociation (TGD) in difficult clinical situations. METHODS: The medical records
      of 11 neurologically normal children treated with TGD and gastrostomy after
      failure of conventional procedures between 1999 and 2004 were reviewed with
      respect to demographic data, initial diagnosis, previous operations,
      postoperative complications, feeding pattern, and follow-up. RESULTS: There were
      7 males and 4 females. The mean age at operation was 52.7 months (24 to 72 m).
      The indications were severe colo-oesophageal reflux in 3; 1 post-fundoplication
      necrotic stomach; 1 gastric remnant after subtotal gastrectomy for bleeding; 1
      microgastria; 2 with severe oesophageal obstruction following repeated failed
      repair of congenital stenosis of the oesophagus and after fundoplication; 1
      congenital short oesophagus with left-sided congenital diaphragmatic hernia; and
      2 with severe dysfunctional oesophagus following repair of congenital tracheo
      oesophageal cleft. Full oral or gastrostomy feeding was established by the 5th
      postoperative day. The average follow-up was 47.2 months (24-72 months). There
      were 4 late deaths in the group: 2 with respiratory failure, 1 with sepsis
      secondary to peritonitis (small bowel herniation into the thorax) and 1 with
      pneumococcal infection. Seven patients are alive and thriving with markedly
      reduced episodes of chest infections and hospitalizations. CONCLUSIONS: In this
      study TGD presented with no peri-operative morbidity and mortality and had good
      long-term results. The procedure offers a safe alternative for neurologically
      normal children after the failure of conventional surgical procedures.

PMID- 17211786
TI  - Non stenotic food impaction due to eosinophilic esophagitis: a potential surgical
      emergency.
AB  - AIM: Eosinophilic esophagitis (EoE) is an emergent condition in which a mucosal
      infiltrate of > 20 eosinophils per high power microscopic field is accompanied by
      motor disturbances that may cause food impaction in the absence of esophageal
      stricture. We report a series of such cases to point out the potential
      involvement of pediatric surgeons in diagnosis and treatment. Furthermore, data
      on the motor function of the esophagus investigated manometrically is included.
      MATERIAL AND METHODS: Thirteen patients with EoE were referred to our emergency
      room for acute food bolus impaction. Their median age at diagnosis was 12 years
      (range 7.6-14.4). History of allergy, endoscopy with biopsy and esophageal
      function (24-h combined ambulatory manometry with simultaneous pH-metry) were
      investigated. RESULTS: In 7 patients emergency endoscopic extraction of the
      impacted bolus was necessary. Allergic tests were positive in eight patients. The
      pH probe showed gastroesophageal reflux in two cases. Upon endoscopy, typical
      features of EoE (esophageal trachealization and whitish papular exudates) were
      found. Ambulatory 24-h manometry revealed abnormal motility of the distal
      esophagus with strikingly high amplitudes (> 150 mmHg) and long duration (> 7
      sec) of the waves, particularly during the night. Six patients responded rapidly
      to steroids and/or antiallergic treatment. The remaining patients had a good
      outcome with dietary treatment alone. CONCLUSIONS: EoE is an emergent condition
      that may involve the pediatric surgeon in both the diagnosis and treatment.
      Typical endoscopic findings and biopsy are required for proper diagnosis.
      Ambulatory manometry reveals a marked propulsive dysfunction that explains
      impaction. This dysfunction is reversible, since the symptoms usually disappear
      with steroids or antiallergic treatment.

PMID- 17211787
TI  - Nutritional status after intestinal transplantation in children.
AB  - INTRODUCTION: The management of children receiving small bowel grafts involves
      potentially life-threatening complications that affect their nutritional status.
      The aim of this paper was to define these factors and their influence on
      nutritional outcome. PATIENTS AND METHODS: Patients with intestinal failure (IF)
      who received an isolated small bowel transplantation (SBT) or small bowel/liver
      transplantation (SBLT) at our hospital during the last 6 years were reviewed for
      weight Z-score, biochemical nutritional parameters, total parenteral nutrition
      (TPN) weaning, catheter-related sepsis, rejection and steroid treatment. RESULTS:
      Twenty patients, 11 females and 9 males, received a SBT or a SBLT and survived
      the postoperative period; in the present study we only included 11 children with
      follow-up periods longer than 1 year. Seven males and 4 females with a mean age
      of 4.5 years (range, 1 to 20 years) received 6 SBLT and 5 SBT. Nine (82%) were
      weaned from TPN to an amino-acid or peptide enteral formula during the first 6
      months after surgery. During the first year there was a significant increase in
      total protein from 5.11 +/- 1.8 mg/dl to 6.1 +/- 1.5 mg/dl (p < 0.05) and an
      increase in albumin from 3.8 +/- 0.9 mg/dl to 4.5 +/- 1.1 mg/dl (p < 0.05). There
      was an increase in weight Z-score in 9 patients (82%) during the first year. Mean
      Z-score improved from - 2.6 +/- 1 at transplant to - 1.0 +/- 0.6 (p < 0.05) after
      1 year. Three patients (27.2%) had at least one rejection period, which was
      treated with steroids alone or in combination. Mean weight Z-score 1 year after
      surgery was - 0.9 +/- 0.6 for patients without rejection and - 1.24 +/- 0.8 for
      those with at least one rejection episode treated with steroids (p > 0.1). Four
      patients (36%) had at least one catheter-related sepsis episode. Mean weight Z
      score 1 year after surgery was - 1.01 +/- 0.6 for patients without catheter
      related sepsis and - 1.24 +/- 0.8 for those with at least one catheter-related
      sepsis episode (p > 0.1). CONCLUSIONS: There was a significant improvement in
      weight Z-score and biochemical nutritional parameters 1 year after receiving a
      small bowel graft. No influence of steroids or catheter-related sepsis on
      children's nutritional status was noted 1 year after surgery, although this point
      will need further evaluation.

PMID- 17211788
TI  - Submucosal plexus of dilatated gut disappears after ligation in chicken embryos:
      preliminary results.
AB  - INTRODUCTION: Dilatation and impaired function of the gut is a condition often
      seen in newborns with bowel obstruction caused by intestinal atresia. In a
      previous experimental study in chicken embryos, we established a model to study
      ultrastructural changes during the development of the enteric nervous system
      after small bowel ligation. The aim of this study is to investigate the changes
      of the enteric nervous system (ENS) after gut ligation. METHODS: 56 chicken
      embryos were investigated. In the operation group fertilized eggs and the
      allantoic membrane were opened and the small bowel was ligated on embryonal day
      (ED) 11. The controls were sham-operated. The gut was prepared and harvested for
      analysis on ED 11, 12, 13, 14, 15, 16, 17 and 18. Silver staining or staining of
      the specimens for acetylcholinesterase (AchE) was performed. RESULTS: A marked
      dilatation of the bowel was observed three days after operation (ED 14). The
      submucosal (PSM) and myenteric plexus (PM) appeared normal at this time, however
      silver staining showed rarification of the neuronal axonal network between the
      myenteric and submucosal plexus. Later, on ED 16 an additional rarification of
      the submucosal plexus was also seen in the operation group using AchE staining,
      compared to the controls. DISCUSSION: The data suggest that distension of the gut
      hinders normal development of the ENS in the gut ligation model of chicken
      embryos. The changes were observed sequentially, starting with rarification of
      the axonal network between the PM and PSM. Future studies will be required to
      show whether the changes of the ENS are reversible.

PMID- 17211789
TI  - Liver transplantation for malignant tumours in children.
AB  - OBJECTIVE: The object of this study was to analyse our results with liver
      transplantation (LTX) for primitive malignant unresectable liver tumours in
      children and to discuss the controversial indications, based on our experience.
      METHODS/PATIENTS: We report on 12 patients, aged 6 months to 14 years, with
      hepatic malignant tumours: 11 with hepatoblastoma and 1 with fibrolamellar
      hepatocelullar carcinoma without cirrhosis. LTX was the primary treatment in 10
      patients (PRETEXT IV or any grade, if there was extension to the retrohepatic
      vena cava, 3 hepatic veins or portal vein) and a rescue therapy after recurrence
      for 1 and for persistence of unresectable macroscopic residuals in 2 patients.
      One of the patients who underwent a LTX as primary therapy had lung metastases
      previously resolved with chemotherapy. We used entire liver (n = 5), left lateral
      segment from cadaveric donor (n = 3), living related donor (n = 3; 2 segments II
      III and 1 right lobe) and left lateral segment from split liver (n = 1). All
      children received chemotherapy prior and post transplantation following the
      SIOPEL protocol. We analysed procedure tolerance, survival, recurrence rate,
      disease-free period and risk factors for adverse evolution. RESULTS: All patients
      overcame LTX and no early graft loss was recorded. Two cases died because of
      tumour relapse, 1 after primary LTX and 1 after rescue LTX (survival rate of both
      groups, 90% and 50%). Graft and patient survival rates at 1 year, 3 years, 5
      years and 14 years were 91%, 91%, 82% and 82% respectively. The boy who presented
      with lung metastases developed new ones one year after LTX that were removed and
      he is currently free of disease. The disease-free period has a probability at 1,
      3 and 5 years of 91%, 75% and 75%, respectively. Tumour tissue persistence was
      the only risk factor for an adverse clinical course in our series. CONCLUSIONS:
      LTX is a reasonable therapeutic approach for unresectable malignant liver
      tumours, providing outcomes comparable to those for resectable tumours. Results
      obtained with LTX are better when it is used as a primary treatment than when
      used as a rescue procedure. Proper staging and early referral to centres with
      enough expertise optimise the results. LTX for patients with lung metastases
      could be a controversial option. Living related-donor transplantation is an
      excellent alternative to avoid disease progression while on the waiting list for
      cadaveric donors.

PMID- 17211790
TI  - Nonparasitic splenic cysts in children: a multicentric study.
AB  - PURPOSE: Nonparasitic splenic cysts (NPSCs) are uncommon in children. The aim of
      this multinational and multicentric study was to present the authors' experience
      as well as the changing trends in the management of NPSCs over the last 25 years.
      MATERIAL AND METHODS: From 1981 to 2005, 50 children or adolescents were
      surgically treated for NPSCs in 6 paediatric surgical centres in four European
      countries. The medical records of these 50 patients with NPSCs were reviewed
      retrospectively. RESULTS: Twenty-six male and 24 female patients were operated
      on. Age at surgery ranged from 1 to 17 years (mean 11.9). Seventeen patients were
      symptomatic. Six total (4 open and 2 laparoscopic) and 26 partial (22 open and 4
      laparoscopic) splenectomies were performed. Laparoscopic fenestration or
      deroofing and open cystectomy was carried out in 9 patients, respectively.
      Histological findings revealed the lesion to be an epidermoid cyst (n = 28), a
      pseudocyst (n = 15) or a mesothelial cyst (n = 2). In 5 patients haemangioma or
      lymphangioma was the pathological diagnosis. At a mean follow-up of 2.9 years,
      residual cysts were found in 8 laparoscopically treated patients, 4 of whom
      required re-do laparoscopy or open surgery. CONCLUSIONS: Over the last two
      decades, the surgical treatment of NPSCs has changed from a formerly customary
      total splenectomy to spleen-conserving procedures, such as total cystectomy with
      or without partial splenectomy or partial cystectomy. These therapeutic
      modalities can be performed laparoscopically, if technically possible.
      Fenestration or deroofing of the cyst resulted in a high recurrence rate (7/9).

PMID- 17211791
TI  - Rectal prolapse of intussusception--a single institution's experience.
AB  - AIM: The objective was to study the clinical presentation and outcome of
      intussusceptions prolapsing rectally. METHODS: A retrospective analysis was done
      of 198 children who presented with intussusception at a single institution over a
      5-year period. Of this group, the data of children with intussusception
      prolapsing rectally was studied. RESULTS: The incidence of prolapsing
      intussusception in this series was 8%. All 16 patients were infants with an
      average age of 5 months. The most common presenting features were rectal bleeding
      and abdominal mass. Only 56% of children had abdominal pain. 4/16 children had
      abdominal distension and 4 had dehydration. The duration of symptoms was less
      than 48 hours in 14/16 patients. Air enema reduction (AER) was attempted in 14/16
      patients and was successful in 8 patients. The success rate of AER was 57%. One
      patient developed a perforation during AER. Manual reduction was done in six
      patients who failed AER and in two patients in whom AER was not attempted because
      of prolonged duration of symptoms (> 48 hrs). There were no recurrences in this
      series. CONCLUSION: The incidence of intussusceptions prolapsing rectally is high
      in this series. It can present in the absence of the cardinal symptoms of
      intussusception. A high index of clinical suspicion is necessary to make the
      diagnosis. AER is often successful and must be attempted in children who do not
      have contraindications for this procedure.

PMID- 17211792
TI  - Diffuse intraabdominal desmoplastic small round cell tumor: a ten-year
      experience.
AB  - BACKGROUND: Intraabdominal desmoplastic small round cell tumors (IDSRCT) are rare
      in children and predominantly affect male adolescents and young adults. We
      present our experience in the management of five children with diffuse IDSRCT,
      managed with aggressive chemotherapy, surgery, radiotherapy and peripheral blood
      stem cell transplantation. MATERIAL AND METHODS: During the last decade five
      patients, four males and one female (mean age 9.6 years), with diffuse IDSRCT
      were managed in our department. The main symptoms were abdominal distention,
      vague abdominal pain, and vomiting. Three patients with inoperable tumor on
      admission were submitted initially to open biopsy followed by aggressive
      chemotherapy. Regression of the tumor was followed by a second laparotomy and
      radical excision of any macroscopically distinguishable masses, followed by
      chemotherapy. In the remaining two patients a debulking procedure was done
      initially, followed by chemotherapy. The accurate diagnosis of the disease was
      established by immunohistochemistry, additionally confirmed in the last two
      patients by molecular analysis. RESULTS: Three patients who had radical excision
      of the tumor and adjuvant chemotherapy had recurrence after two to six months. In
      the remaining two patients, recurrence was evident after two and eighteen months,
      respectively, following debulking. In addition, one patient with recurrence
      received radiotherapy and two others underwent peripheral blood stem cell
      transplantation. All but one patient died within three years from diagnosis. The
      last patient, who was submitted to a debulking procedure, is still alive eight
      months after the operation. CONCLUSIONS: Intrabdominal desmoplastic small round
      cell tumor is a highly aggressive malignancy with a very poor prognosis.
      Multiagent chemotherapy usually leads initially to a temporary regression of the
      tumor, but recurrence is the rule. Radical surgical excision, radiotherapy and
      peripheral blood stem cell transplantation does not seem to improve prognosis
      significantly. Despite all therapeutic modalities the outcome is dismal and
      surgical efforts can be considered only as palliative.

PMID- 17211793
TI  - The use of human chorionic gonadotropin (HCG) for penile reconstruction in
      bladder exstrophy and total epispadias patients.
AB  - OBJECTIVES: The effect of intramuscular human chorionic gonadotropin (HCG)
      administration on penile enlargement before genital surgery, its influence on
      penile skin histology and testicular descent were investigated. METHODS: We
      examined 45 male patients (median age, 8 months; range 3-28) with total
      epispadias and classic bladder exstrophy, combined with cryptorchidism. 30
      patients were administered 250-500 IU HCG intramuscularly 2 times per week for 3
      weeks before reconstructive surgery. Skin biopsies were obtained for human
      epidermal growth factor (EGF) and human epidermal growth factor receptor
      (Her2/neu) determination. Skin specimens of the prepuce of 18 circumcised
      patients were used as controls. Post treatment testicle position was evaluated.
      RESULTS: HCG caused a mean increase in penile length of 1.8 cm (p < 0.01) and in
      circumference of 1.2 cm (p < 0.05) as well as improved local vascularity in all
      patients. Compared to the controls, the penile skin of exstrophy/epispadias
      patients showed a significant decrease in the average amount per field of EGF and
      Her2/neu positive material (controls 81% [mean 79, SE 2.3] vs. 31% [mean 28, SE
      3.6; p < 0.001]). Treatment with HCG led to an increase in average EGF and
      Her2/neu positive material by 10% (mean 8, SE 2; p < 0.05). The potential side
      effects of HCG treatment were monitored 3 to 6 months postoperatively. Basal
      testosterone and LH levels were obtained in patients before and during therapy
      and postoperatively. Testicular descent was achieved in 21 patients (70%). No
      significant side effects or complications were encountered in any of our
      patients. CONCLUSION: Mean EGF and Her2/neu values are decreased in the penile
      skin of exstrophy/epispadias patients. The use of preoperative HCG administration
      leads to an increase in EGF and Her2/neu values and significantly contributes to
      successful reconstruction in these patients, especially in cases with a paucity
      of penile skin and in patients who have undergone previous repairs. Temporary
      penile stimulation by HCG in patients with bladder exstrophy combined with
      cryptorchidism allows the penile operation to be carried out earlier and
      contributes to testicular descent while demonstrating negligible side effects.

PMID- 17211794
TI  - Long-term outcome of elastic stable intramedullary fixation (ESIF) of femoral
      fractures in children.
AB  - In 1993 a prospective data collection of all femoral fracture in children below
      16 years of age was initiated in 4 hospitals in the Netherlands. Follow-up was at
      least two years, with the aim to evaluate leg length discrepancies (LLD). Over a
      period of 10 years, we included 136 patients < 16 years of age with femoral
      fractures. Seventy-one patients who were treated with an ESIF-(Elastic Stable
      Intramedullary Fixation) nail were studied: 44 boys and 27 girls, between the
      ages of 3-16 years, 23 of which had multiple injuries. Five patients had a Ist or
      IInd degree open fracture. The average length of stay (LOS) of children with an
      isolated fracture, was 10 days, and in case of multiple injuries: 12 days. Intra
      operative complications were: a broken drill in 2 and an open reduction in 6
      cases. Two patients with superficial wound infection were successfully treated
      with antibiotics. Seven patients had knee complaints of the nails, of which 3 had
      actually been displaced. Three other patients showed displacement of the nails at
      X-ray, but had no complaints. At six months follow-up, at the time of removal of
      the nails, 10 patients had a leg length discrepancy (LLD) exceeding 10 mm. Three
      children had a clinically significant rotational deformity at this time. Two and
      a half years after injury 6 patients showed a persistent LLD of more than 10 mm.
      In all 6 the fractured limb was longer. At ten years of follow-up the LLD
      persisted in 5 patients. One patient had a persistent clinically significant
      rotational deformity of more than 10 degrees . The advantages of ESIF-nails are:
      reduction of hospital stay and rapid mobilisation. The disadvantages: two
      operations (for insertion and removal) with a risk of complication. Long-term
      follow-up, preferably till growth stops, is necessary to conclude whether
      persistent lengthening of the fractured limb remains a problem.

PMID- 17211795
TI  - A new endoscopic procedure for membranectomy of fenestrated duodenal membranes.
AB  - AIM OF THE STUDY: We describe a new endoscopic procedure for membranectomy of
      fenestrated duodenal membranes. METHODS: With the patients under general
      anesthesia and tracheally intubated, a flexible video-panendoscope was introduced
      into the second portion of the duodenum. The fenestrated membrane was visualized
      and a triple-lumen stone extraction balloon of 15 mm was inserted through the
      fenestration. After the balloon was insufflated, gentle traction was performed in
      order to expose the fenestrated membrane and differentiate it from the normal
      duodenal wall. The orifice was dilated in order to introduce the endoscope and
      localize the Vater's ampulla. A sphincterotome was used to carry out one or two
      incisions of 1.5 to 2 cm in the membrane in the opposite direction to the
      ampulla. RESULTS: The procedure was successfully performed in five patients with
      a mean surgical time of 50 minutes. None of the patients complained of
      postoperative pain. Peristalsis was not affected, and patients started intake of
      oral fluids at approximately 24 hours. On discharge patients were completely
      asymptomatic, and four patients were followed up for one year following the
      procedure and remained asymptomatic. One patient who was also asymptomatic did
      not continue follow-up longer than two weeks after the procedure. CONCLUSION:
      Endoscopic membranectomy of duodenal membranes is a safe and effective procedure
      that reduces surgical times, postoperative fasting times and the length of
      hospitalization, and probably has no postoperative complications.

PMID- 17211796
TI  - Congenital solitary liver cysts.
AB  - AIM: The aim of the study was to describe clinical and pathological findings in
      children with rare congenital solitary liver cyst. MATERIAL AND METHODS: Six
      children with congenital liver cyst were treated at the authors' institution from
      1995 to 2002. Clinical records and operative findings of these patients were
      reviewed retrospectively. RESULTS: Age at presentation ranged from neonatal to 14
      years, and there were four girls and two boys. Hepatomegaly was the most common
      symptom in neonates while the older children presented with abdominal pain.
      Ultrasound was conclusive for diagnosis in all children, prenatal ultrasound in
      three. Intrahepatic cyst was found in five children. Partially extrahepatic cyst
      in the porta hepatis was found in one. The cyst diameters varied from 8 to 10 cm.
      Cysts were excised via an open abdominal approach in all patients. Histological
      findings confirmed the diagnosis of congenital liver cyst. Columnar epithelium
      was found in newborns while atrophic changes of epithelial lining were seen in
      older children. In a case of a 13-year-old girl the cyst was lined by metaplastic
      squamous epithelium with foci of slight dysplasia. Immunohistochemical studies
      were available in three recent children with positive findings in all of them.
      The postoperative course was uneventful in all patients. The follow-up period
      ranged from 36-120 months and no recurrence was observed. CONCLUSION: With
      appropriate selection of symptomatic patients, total excision of a congenital
      liver cyst is a safe procedure with excellent long-term results. Given the
      possibility of malignant degeneration of a congenital liver cyst we recommend its
      surgical excision in most cases.

PMID- 17211797
TI  - A unique opportunity for the operative treatment of high anorectal malformations:
      laparoscopy.
AB  - BACKGROUND/PURPOSE: Georgeson et al. have reported a new operative technique for
      the treatment of high anorectal malformations (ARM) instead of posterior sagittal
      anorectoplasty (PSARP). With this new operative technique, anorectal pull-through
      is performed without a posterior sagittal incision with laparoscopic assistance.
      Herein we report our experience with laparoscopy-assisted anorectal pull-through
      (LAARP). METHODS: The hospital and the digital video records of 4 high ARM male
      patients who underwent LAARP between January 2002 and June 2004 were evaluated
      retrospectively. The LAARP procedure was accomplished as described by Georgeson
      et al. Dilatation of the neoanus was started on the 15th postoperative day and
      was continued twice daily until the desired anal diameter had been reached. The
      colostomies were closed thereafter. RESULTS: LAARP was performed in the presence
      of colostomy in four patients. The first two patients are passing stools two or
      three times a day. A bowel management program has been initiated for the third
      patient, who is 4 years old. The last patient still has a colostomy. CONCLUSIONS:
      The laparoscopically excellent visualization of the pelvic musculature,
      especially of the pubococcygeal muscles, provides a great opportunity for
      accurate placement of the rectum in its anatomically precise place, without
      dividing the sphincteric muscle complex. Although there is not enough data
      regarding fecal continence after LAARP, we think that LAARP provides a unique
      opportunity for the operative treatment of high ARM and should be the first
      choice procedure for the operative treatment of high ARM.

PMID- 17211799
TI  - The role of despotism and heritability in determining settlement patterns in the
      colonial lesser kestrel.
AB  - Avian colony size variation is an evolutionary puzzle in terms of unequal fitness
      payoffs. We used a long-term marked lesser kestrel (Falco naumanni) population,
      where individual fitness increases with colony size, to test whether subordinates
      are evicted despotically from the largest colonies. Yearlings were smaller and
      lighter, were more attacked than expected, and lost most disputes over nest holes
      with older birds. Agonistic interactions increased with colony size;
      consequently, most first breeders recruited in colonies smaller than those at
      which they first tried to settle. As expected when subordination is a transient
      state, birds dispersed to a larger colony as they got older even after breeding
      successfully. The population consequences of these behavioral processes were that
      the relative frequency of yearlings and first breeders decreased with colony
      size. At the same time, breeding colony size was repeatable within individuals,
      so we estimated the amount of heritable variation in this trait. Estimates of
      heritability derived from parent-offspring and full-sib analyses were
      consistently high (h2=0.53) when individuals reached asymptotic morphological
      values and presumably overcame subordinate transient states. Age-related
      dominance asymmetries masked resemblance among relatives in colony size, but both
      phenomena seem to coexist in this population and explain a considerable
      proportion of colony size variation.

PMID- 17211800
TI  - Divergent host plant adaptation and reproductive isolation between ecotypes of
      Timema cristinae walking sticks.
AB  - Theoretical and empirical studies have demonstrated that divergent natural
      selection can promote the evolution of reproductive isolation. Three unresolved
      questions concern the types of reproductive barriers involved, the role of
      geography, and the factors determining the extent of progress toward complete
      speciation. Here I synthesize studies of Timema cristinae host plant ecotypes to
      address these issues. The approach is to compare the magnitude of multiple
      reproductive barriers among different ecological and geographic scenarios, where
      pairs of populations within each scenario are the unit of replication.
      Application of this approach to T. cristinae revealed that divergent host
      adaptation can promote the evolution of diverse reproductive barriers, including
      those that are not inherently ecological. Gene flow in parapatry tended to
      constrain divergence, with the notable exception of the reinforcement of sexual
      isolation. Thus, geography affected progress toward speciation but did not
      influence all reproductive barriers in the same way. Studies of any single pair
      of taxa often capture only certain stages of the speciation process. For example,
      reproductive isolation between T. cristinae ecotypes is incomplete, and so only
      the stages before the completion of speciation have been examined. Studies of
      more divergent taxa within the genus are required to determine the factors that
      complete speciation.

PMID- 17211801
TI  - Relating environmental variation to selection on reaction norms: an experimental
      test.
AB  - Theoretical models predict that selection on reaction norms should depend on the
      relative frequency of environmental states experienced by a population. We report
      a laboratory experimental test of this prediction for thermal performance curves
      of larval growth rate in Pieris rapae in relation to their thermal environment.
      We measured short-term relative growth rate (RGR) for each individual at a series
      of five temperatures, and then we assigned individuals randomly to warm or cool
      selection treatments, which differ in the frequency distributions of
      environmental temperatures. Selection gradient analyses of two independent
      experiments demonstrated significant positive selection for increasing RGR,
      primarily through its effects on survival to adulthood and on development rate.
      In both the warm and cool selection treatments, the magnitude of directional
      selection on RGR was consistently greater at lower (suboptimal) temperatures than
      at higher temperatures; differences in selection between the treatments did not
      match model predictions. The temporal order and duration of environmental
      conditions may affect patterns of selection on thermal performance curves and
      other continuous reaction norms, complicating the connections between variation
      in environment, phenotype, and fitness.

PMID- 17211802
TI  - Consequences of heat hardening on a field fitness component in Drosophila depend
      on environmental temperature.
AB  - Heat hardening increases thermal resistance to more extreme temperatures in the
      laboratory. However, heat hardening also has negative consequences, and the net
      benefit of hardening has not been evaluated in the field. We tested short-term
      heat hardening effects on the likelihood of Drosophila melanogaster to be caught
      at different temperatures at baits in field sites without natural resources. We
      predicted that hardened flies should be more frequently caught at the baits at
      high but not low temperatures. Under cool conditions, flies hardened at 36
      degrees C, and to a lesser extent at 34 degrees C, were less frequently caught at
      baits than nonhardened flies a few hours after release, indicating a negative
      effect of hardening. In later captures, negative effects tended to disappear,
      particularly in males. Under warm conditions, there was an overall balance of
      negative and positive effects, though with a different temporal resolution. Under
      very hot conditions, when capture rates were low, there was a large benefit of
      hardening at 36 degrees C and 34 degrees C but not 33 degrees C. Finally, based
      on climatic records, the overall benefit of hardening in D. melanogaster is
      discussed as an evolved response to high temperatures occasionally experienced by
      organisms at some locations.

PMID- 17211803
TI  - Bet hedging via seed banking in desert evening primroses (Oenothera, Onagraceae):
      demographic evidence from natural populations.
AB  - Bet hedging is one solution to the problem of an unpredictably variable
      environment: fitness in the average environment is sacrificed in favor of lower
      variation in fitness if this leads to higher long-run stochastic mean fitness.
      While bet hedging is an important concept in evolutionary ecology, empirical
      evidence that it occurs is scant. Here we evaluate whether bet hedging occurs via
      seed banking in natural populations of two species of desert evening primroses
      (Oenothera, Onagraceae), one annual and one perennial. Four years of data on
      plants and 3 years of data on seeds yielded two transitions for the entire life
      cycle. One year was exceptionally dry, leading to reproductive failure in the
      sample areas, and the other was above average in precipitation, leading to
      reproductive success in four of five populations. Stochastic simulations of
      population growth revealed patterns indicative of bet hedging via seed banking,
      particularly in the annual populations: variance in fitness and fitness in the
      average environment were lower with seed banking than without, whereas long-run
      stochastic mean fitness was higher with seed banking than without across a wide
      range of probabilities of the wet year. This represents a novel, unusually
      rigorous demonstration of bet hedging from field data.

PMID- 17211804
TI  - Hierarchical organization via a facilitation cascade in intertidal cordgrass bed
      communities.
AB  - It has recently been proposed that many communities are structured by a hierarchy
      of interactions in which facilitation by foundation species is of primary
      importance. We conducted the first explicit experimental test of this hypothesis
      by investigating the organization of positive interactions on New England
      cobblestone beaches. In this midintertidal community, wave-generated substrate
      instability and solar stress largely limit marine organisms to the shelter of
      cordgrass beds. Cordgrass, which can establish and persist without the aid of
      other foundation species, facilitates a dense assemblage of inhabitants (e.g.,
      mussels, snails, seaweeds) with roots/rhizomes that stabilize substrate and a
      dense canopy that baffles waves and provides shade. Within the cordgrass bed
      community, ribbed mussels further enhance physical conditions and densities of
      other species (e.g., amphipods, barnacles) by providing crevice space and hard
      substrate. We conclude that cordgrass bed communities are hierarchically
      organized: secondary interactions (e.g., facilitation by ribbed mussels) play a
      key role within an assemblage dependent on primary facilitation by the
      independently successful foundation species cordgrass. Our results identify
      emergent indirect positive interactions in the form of facilitation cascades,
      have broad implications for conservation, and help unify existing models of
      community organization that were developed without considering the fundamental
      role of positive interactions.

PMID- 17211805
TI  - The relation between multilocus population genetics and social evolution theory.
AB  - Evolution at multiple gene positions is complicated. Direct selection on one gene
      disturbs the evolutionary dynamics of associated genes. Recent years have seen
      the development of a multilocus methodology for modeling evolution at arbitrary
      numbers of gene positions with arbitrary dominance and epistatic relations, mode
      of inheritance, genetic linkage, and recombination. We show that the approach is
      conceptually analogous to social evolutionary methodology, which focuses on
      selection acting on associated individuals. In doing so, we (1) make explicit the
      links between the multilocus methodology and the foundations of social evolution
      theory, namely, Price's theorem and Hamilton's rule; (2) relate the multilocus
      approach to levels-of-selection and neighbor-modulated-fitness approaches in
      social evolution; (3) highlight the equivalence between genetical hitchhiking and
      kin selection; (4) demonstrate that the multilocus methodology allows for social
      evolutionary analyses involving coevolution of multiple traits and genetical
      associations between nonrelatives, including individuals of different species;
      (5) show that this methodology helps solve problems of dynamic sufficiency in
      social evolution theory; (6) form links between invasion criteria in multilocus
      systems and Hamilton's rule of kin selection; (7) illustrate the generality and
      exactness of Hamilton's rule, which has previously been described as an
      approximate, heuristic result.

PMID- 17211806
TI  - Resolving the paradox of stasis: models with stabilizing selection explain
      evolutionary divergence on all timescales.
AB  - We tested the ability of six quantitative genetic models to explain the evolution
      of phenotypic means using an extensive database compiled by Gingerich. Our
      approach differs from past efforts in that we use explicit models of evolutionary
      process, with parameters estimated from contemporary populations, to analyze a
      large sample of divergence data on many different timescales. We show that one
      quantitative genetic model yields a good fit to data on phenotypic divergence
      across timescales ranging from a few generations to 10 million generations. The
      key feature of this model is a fitness optimum that moves within fixed limits.
      Conversely, a model of neutral evolution, models with a stationary optimum that
      undergoes Brownian or white noise motion, a model with a moving optimum, and a
      peak shift model all fail to account for the data on most or all timescales. We
      discuss our results within the framework of Simpson's concept of adaptive
      landscapes and zones. Our analysis suggests that the underlying process causing
      phenotypic stasis is adaptation to an optimum that moves within an adaptive zone
      with stable boundaries. We discuss the implication of our results for comparative
      studies and phylogeny inference based on phenotypic characters.

PMID- 17211807
TI  - Proximate causes of Rensch's rule: does sexual size dimorphism in arthropods
      result from sex differences in development time?
AB  - A prominent interspecific pattern of sexual size dimorphism (SSD) is Rensch's
      rule, according to which male body size is more variable or evolutionarily
      divergent than female body size. Assuming equal growth rates of males and
      females, SSD would be entirely mediated, and Rensch's rule proximately caused, by
      sexual differences in development times, or sexual bimaturism (SBM), with the
      larger sex developing for a proportionately longer time. Only a subset of the
      seven arthropod groups investigated in this study exhibits Rensch's rule.
      Furthermore, we found only a weak positive relationship between SSD and SBM
      overall, suggesting that growth rate differences between the sexes are more
      important than development time differences in proximately mediating SSD in a
      wide but by no means comprehensive range of arthropod taxa. Except when protandry
      is of selective advantage (as in many butterflies, Hymenoptera, and spiders),
      male development time was equal to (in water striders and beetles) or even longer
      than (in drosophilid and sepsid flies) that of females. Because all taxa show
      female-biased SSD, this implies faster growth of females in general, a pattern
      markedly different from that of primates and birds (analyzed here for
      comparison). We discuss three potential explanations for this pattern based on
      life-history trade-offs and sexual selection.

PMID- 17211808
TI  - Cuckoldry incites cannibalism: male fish turn to cannibalism when perceived
      certainty of paternity decreases.
AB  - Perceived certainty of paternity is expected to influence a male's behavior
      toward his offspring: if he is uncertain of his reproductive success with a
      current brood due to the presence of cuckolders, it may benefit him to invest
      instead in future reproduction. A decrease in perceived certainty of paternity
      incites filial cannibalism (the eating of one's own offspring) in some teleost
      fishes that provide parental care; however, no work has demonstrated that
      cannibalism increases proportionately with increased levels of cuckoldry. Here we
      show for the first time in a fish with no parental care that as the number of
      cuckolders at a spawning event increases, so does the probability that a male
      will cannibalize eggs. In field observations of Telmatherina sarasinorum, a small
      fish endemic to Sulawesi, Indonesia, males increased filial cannibalism behavior
      threefold in the presence of one cuckolder and nearly sixfold in the presence of
      two or more cuckolders. This suggests that males may use detection of cuckolders
      as an indication that the paternity of current offspring has been compromised.

PMID- 17211809
TI  - Use of prey hotspots by an avian predator: purposeful unpredictability?
AB  - The use of space by predators in relation to their prey is a poorly understood
      aspect of predator-prey interactions. Classic theory suggests that predators
      should focus their efforts on areas of abundant prey, that is, prey hotspots,
      whereas game-theoretical models of predator and prey movement suggest that the
      distribution of predators should match that of their prey's resources. If,
      however, prey are spatially anchored to one location and these prey have
      particularly strong antipredator responses that make them difficult to capture
      with frequent attacks, then predators may be forced to adopt alternative movement
      strategies to hunt behaviorally responsive prey. We examined the movement
      patterns of bird-eating sharp-shinned hawks (Accipiter striatus) in an attempt to
      shed light on hotspot use by predators. Our results suggest that these hawks do
      not focus on prey hotspots such as bird feeders but instead maintain much spatial
      and temporal unpredictability in their movements. Hawks seldom revisited the same
      area, and the few frequently used areas were revisited in a manner consistent
      with unpredictable returns, giving prey little additional information about risk.

PMID- 17211810
TI  - The evolution of infidelity in socially monogamous passerines: neglected
      components of direct and indirect selection.
AB  - A recent study by Goran Arnqvist and Mark Kirkpatrick in the American Naturalist
      (165:S26-S37) suggested that female polyandry in birds is not driven by females
      because quantitative genetic approximations of selection demonstrated that
      indirect selection for female infidelity is weaker than natural selection against
      it. Instead, it was argued that extrapair copulations are the result of
      antagonistic selection on male behavior driving female coercion. While the
      approach and framework of the study were very good, the conclusions of the study
      were premature because a number of potential adaptive components of polyandry
      were unaccounted for, and several critical assumptions are unsupported by the
      current empirical data. Our understanding of extrapair paternity in birds, and
      perhaps polyandry in general, will be improved by a better empirical
      understanding of the direct benefits of fertility assurance and postcopulatory
      cryptic female choice and the relationship between polyandry and male investment.
      In addition, we need to develop a greater awareness of the limitations of trying
      to study behavior by proxy in the molecular laboratory. Together, these
      challenges and the framework recently presented should improve our understanding
      of the true function of extrapair paternity in birds.

PMID- 17211812
TI  - Quote but do not misquote the literature.

PMID- 17211813
TI  - Pediatric mechanical circulatory support.
AB  - Over the past two decades clinicians and researchers have sought to bring
      mechanical circulatory support (MCS) to pediatric patients with heart failure.
      ECMO, IABPs, and VADs have all been used in infants and children as a bridge to
      myocardial recovery or as a bridge to transplant. However, until recently, a
      commitment by industry, government, and researchers towards the development of
      pediatric MCS has not been present, especially in the United States. Advancements
      in adult VAD design to smaller, quieter, and fully implantable pumps capable of
      complete outpatient support have sparked curiosity in the application of this
      technology to children. Also, the increasing success of palliating congenital
      heart disease is creating an ever-growing cohort of children and adolescents with
      heart failure. These changing demographics and technological advances have caused
      a refocus of attention. This is most clearly demonstrated by the international
      use of several established MCS pediatric and neonatal systems, by the FDAOs
      increasing proclivity to allow the use of international pediatric VADs in the
      USA, and by the recent National Heart, Lung, and Blood Institute funding of
      several institutions to develop pediatric VADs. This review describes the
      different aspects of pediatric MCS including indications, the features of the
      various VADs, and their current application in children worldwide.

PMID- 17211814
TI  - Uremic pruritus.
AB  - Renal itch is a localized or generalized itch, affecting patients with Chronic
      Renal Failure, where there is no primary skin disease and no systemic or
      psychological dysfunction that might cause pruritus. Uremic pruritus (UP) is an
      unpleasant sensation, rarely appearing in earlier stages of chronic kidney
      disease. Renal transplantation is the definite solution for that problem. The
      prevalence of UP has been reduced during the last years, possibly, due to a more
      efficient dialysis, with more biocompatible filters. During the last decades a
      big number of substances were considered to be etiologic factors of UP, and an
      even bigger number of therapeutic substances appeared with promising potentials
      and conflicting results in the course of their use. The main reason for this
      disorientation is the lack of sound evidence on the pathogenetic mechanisms that
      may potentiate UP. 'Inflammatory' and 'opioid' hypothesis are the best studied
      and the reduction of UP is a fact. Nevertheless the mechanisms of the
      pathogenesis of UP are still under investigation and a long way has to be done in
      order to achieve more definite results.

PMID- 17211815
TI  - Confirmation of high cytokine clearance by hemofiltration with a cellulose
      triacetate membrane with large pores: an in vivo study.
AB  - OBJECTIVE: To confirm in vivo the hypothesis that hemofiltration with a large
      pore membrane can achieve significant cytokine clearance. METHOD: We used a well
      known animal model of endotoxinic shock (0.5 mg/kg of lipopolysaccharide from
      Escherichia Coli over a period of 30 mins). Six pigs were hemofiltrated for 3
      hours with a large pore membrane (78 A pore, 80 kDa cut off) (Sureflux FH 70,
      Nipro, Osaka, Japan). The ultrafiltration rate was 45 ml/kg/min. Samples were
      taken from arterial, venous line and in the ultrafiltrate at T120 and T240. We
      measured concentrations of interleukin 6, interleukin 10 and albumin. RESULTS: At
      T120 and T240, the IL-6 clearances were 22 +/- 7 and 15 +/- 3 ml/min,
      respectively. The IL-6 sieving coefficients were 0.97 and 0.7 at T120 and T240,
      respectively. At T120 and T240, the IL-10 clearances were 14 +/- 4 and 10 +/- 7
      ml/min, respectively. The sieving coefficients were 0.63 and 0.45 at T120 and
      T240, respectively. The concentrations of IL-6 and IL-10 were the same at T0 and
      T240. At T60 and T240, the plasmatic albumin concentrations were 24 +/- 4 g/L and
      23 +/- 4 g/L, respectively (p = 0.13). CONCLUSIONS: In this animal model of
      endotoxinic shock, we confirm the high cytokine clearance observed when
      hemofiltration is applied to a large pore membrane. The loss of albumin seems
      negligible. The impact of such clearances on hemodynamic stability and survival
      remains to be proved.

PMID- 17211817
TI  - Practice pattern of hemodialysis vascular access in Maiduguri, Nigeria.
AB  - BACKGROUND: Despite available evidence based recommendations and guidelines there
      are differences in the preferred type of vascular access in use in different
      localities and geographical regions. This one center study on the practice
      pattern of vascular access was carried out in Maiduguri, Nigeria covering a
      period of the first 5 years of renal care in the area. METHOD: We analysed the
      dialysis and hospital records of consecutive patients that received hemodialysis
      in the renal center during the period between January 2000 and December 2004.
      Data comprised patients' demographics, vascular access used, complications
      encountered during the treatment period. Clinical and laboratory features of the
      patients were also recorded and analysed. RESULTS: The study involved one hundred
      and seventy-nine patients (M:F=2:1) who suffered kidney failure whose cause was
      clinically determined to be mainly due to chronic glomerulonephritis,
      hypertension, obstructive nephropathy and interstitial nephritis. Majority
      presented as late referrals to the nephrologist. Overall 9% of the study
      population used AVFs while 91% used catheters inserted into the femoral or
      internal jugular veins. CONCLUSION: The use of catheters for vascular access was
      the practice in the majority of the patients and this is possibly related to the
      poor survival of the patients on hemodialysis. Socioeconomic circumstances of the
      patients in turn largely influenced the rate of AVF use.

PMID- 17211816
TI  - Leptin and beta2-microglobulin kinetics with three different dialysis modalities.
AB  - BACKGROUND: Leptin is a protein produced by fat cells and involved in body weight
      regulation. In patients with normal kidney function, leptin has been considered
      an independent predictor of cardiovascular events. In uremic patients, leptin in
      plasma serum was assumed to be associated with malnutrition, inflammation and
      atherosclerosis. Because of its molecular weight and characteristics, leptin can
      be considered as a protein-bound uremic retention solute. Some authors have
      reported the possibility of decreasing the serum leptin concentration with high
      flux membranes, but limited data are available on the elimination with medium
      flux membranes or alternative dialysis strategies such as hemodiafiltration.
      METHODS: We evaluated the kinetics of leptin and beta2m in a study of 18 chronic
      hemodialysis patients using low-flux, medium-flux and high-flux biocompatible
      membranes, the last one used in hemodiafiltration (HDF). Blood samples for leptin
      and beta2m were collected pre- and post-treatment and 30 minutes after the end of
      treatment, over a 1-week period that included 3 dialysis sessions. Clearances of
      leptin and beta2m across the dialyzer were also determined directly from the
      arterial and venous blood concentrations 60 and 210 minutes after starting
      dialysis. RESULTS: At baseline, all groups showed similar leptin (18.8+/-4.4
      ng/mL) and beta2m concentrations (29.2+/-7.1 ng/mL). After a single dialysis
      session, a reduction of both solutes was observed with HDF (39.8+/-1.9%, 78.1+/
      4.9) and medium flux membranes (18.2+/-0.9%, 52.2+/-1.7%), whereas the
      concentrations remained unchanged with the low-flux membranes. After one-week
      period, a trend of reduction of plasma pre dialysis leptin and beta2m were
      observed with HDF and medium flux membranes. At 60 minutes, HDF showed the best
      instantaneous clearance across the filter for leptin (56.2+/-10.1 ml/min) and
      beta2m (75.3+/-4.4 ml/min). The magnitude of post dialysis rebound of leptin at
      30 min was variable and strongly correlated with the instantaneous clearance of
      the solute (r2= 0.88). CONCLUSIONS: Leptin serum concentration can be influenced
      by dialysis modalities and membrane permeability; data on rebound suggest a
      multicompartimental kinetic of leptin similar to beta2m. Leptin removal, as
      measured by the reduction rate, can be considered as an index of dialysis
      efficiency for protein-bound uremic retention solutes.

PMID- 17211818
TI  - Virtual respiratory system for education and research: simulation of expiratory
      flow limitation for spirometry.
AB  - BACKGROUND: Due to economic and ethical problems, virtual organs may appear more
      convenient than experiments on animals or limited investigations on patients. In
      particular, a virtual respiratory system (VRS) may be useful for tasks such as
      respirators and support methods testing, education, staff (medical and technical)
      training, (initial) testing of scientific hypotheses. METHODS: A comparative
      study of simulated and real spirometric results for different patient states
      (healthy lungs, restrictive lung disease, and obstructive lung disease of
      different localization and degree) was performed. The volume-flow curve and such
      standard parameters as FEV1, FEV1%VC, MEF75 etc. were analyzed. RESULTS: A
      mathematical description of collapsing bronchi was proposed. All fundamental
      phenomena present during spirometry also appeared in VRS, especially
      characteristic dependence between lung volume and air flow for forced expiration.
      In particular, both airway resistance and the flow limitation were described with
      one formula derived from commonly known dependence of the resistance on lung
      volume. Generally there were no significant differences between simulated results
      and those seen in clinical practice. Only simulation of obstruction in upper
      airways gave incorrect results, which suggested a different flow limitation
      mechanism (perhaps wave-speed limitation). CONCLUSIONS: Our VRS can already be
      used in medical education, e.g. courses of spirometry, and in some other
      applications. It seems that the significance of the wave-speed criterion has been
      overestimated.

PMID- 17211819
TI  - Wireless patient monitoring system for a moving-actuator type artificial heart.
AB  - In this study, we developed a wireless monitoring system for outpatients equipped
      with a moving-actuator type pulsatile bi-ventricular assist device, AnyHeart. The
      developed monitoring system consists of two parts; a Bluetooth-based short
      distance self-monitoring system that can monitor and control the operating status
      of a VAD using a Bluetooth-embedded personal digital assistant or a personal
      computer within a distance of 10 meters, and a cellular network-based remote
      monitoring system that can continuously monitor and control the operating status
      of AnyHeart at any location. Results of in vitro experiments demonstrate the
      developed system's ability to monitor the operational status of an implanted
      AnyHeart.

PMID- 17211820
TI  - Self-management protocol for a moving-actuator type artificial heart.
AB  - In this paper, we describe the development of a self-management protocol for a
      controller of a moving-actuator type artificial heart, AnyHeart. The developed
      protocol analyzes motor current signals and detects abnormal pumping statuses. If
      preset abnormal pumping statuses are detected by an implemented algorithm, a
      controller triggers an emergency management procedure and transmits an alarm
      message to predetermined medical and engineering staffs via a cellular phone
      network to notify them of an abnormal pumping status occurrence and its likely
      cause. Results of in vitro performance experiments showed that the developed
      protocol can detect simulated abnormalities in motor current, manage the
      operating status of the blood pump during an emergency, and transmit an alarm
      message as desired.

PMID- 17211821
TI  - Improved neo-endothelialization of small diameter ePTFE grafts with titanium
      coating.
AB  - BACKGROUND: Patency of small synthetic bypass grafts is inferior compared to
      autologous grafts for revascularization procedures. Titanium coating of foreign
      surfaces has shown to decrease thrombogenicity, enhance biocompatibility and
      promote adhesion of endothelial cells. The aim of this study was to test the
      effect of titanium coating of small diameter ePTFE grafts on short term patency,
      neo-endothelialization and neointimal proliferation. METHODS: Bilateral carotid
      graft interposition was performed in 5 pigs with uncoated (n=5) and titanium
      coated (n=5) ePTFE grafts (internal diameter=4 mm, length=5 cm), thus each pig
      served as its own control. At the end of the study (30 +/- 3 days), patency and
      stenosis severity was assessed by carotid angiography. Animals were sacrificed
      and grafts were excised for histology and scanning electron microscopy.
      Morphometry of histologic sections was carried out to determine neointimal
      proliferation and percentage of neo-endothelial coverage. RESULTS: Patency rate
      was 80% for uncoated and titanium-coated grafts. Quantitative angiography did not
      show any significant difference in lumen size between two groups. Morphometry
      revealed a significantly higher cellular coverage with CD31 positive endothelial
      cells for titanium-coated (84 +/- 19%) than uncoated grafts (48 +/- 26%,
      p<0.001). There was a non significant trend (p=0.112) towards increased
      neointimal proliferation in titanium-coated (94 +/- 61 micron2/micron) compared
      to uncoated grafts (60 +/- 57 micron2/micron). CONCLUSIONS: Patency rate in
      uncoated and titanium-coated ePTFE grafts is similar at one month. However,
      titanium coated grafts show a significant improvement in neo-endothelialization
      compared to uncoated grafts.

PMID- 17211822
TI  - Resin-based dentin restorative materials under accelerated ageing: bio-functional
      behavior.
AB  - OBJECT: The aim of the present study was the evaluation of the effect of
      different polishing and finishing procedures on Filtek Z250 FZ ESPE restorative
      material. Particularly, the consequence of artificial aging (UV-irradiation) on
      this resin-based dental material was investigated determining also its outcome on
      cell behavior. METHODS: 96 specimens of restorative material were prepared using
      a light emitting diode curing unit and randomly divided into four finishing and
      polishing groups: (I) No treatment (FZ); (II) Identoflex rubbers (ID); (III)
      Enhance System (EN) and (IV) Sof-Lex Pop-on XT discs (SF). The surface morphology
      of native and artificially aged materials was assessed with Atomic Force
      Microscopy (AFM) and Scanning Electron Microscopy (SEM). FTIR and biological
      (biocompatibility and bacterial adhesion) analyses were also performed. RESULTS:
      Among all, the ID procedure represented an acceptable compromise for efficiency
      of polymerization and biocompatibility both before and after artificial ageing.
      SF and EN techniques showed better interactions with the biological environment.
      CONCLUSION: UV artificial ageing of the tested specimens has shown an
      acceleration of the surface degrading processes, favoring a possible decrease in
      the mechanical properties and the release of toxic free radicals. Finishing and
      polishing procedure seemed to affect the photodegrading pathways, even though no
      differences among the techniques were observed. As the cytotoxicity of materials
      undergoing accelerated aging is relevant, further improvement of dental
      restorative materials are required to limit the long-term biological damage.

PMID- 17211823
TI  - In vitro evaluation of bio-functional performances of Ghimas titanium implants.
AB  - Titanium is the most widely used material for dental implants. The natural
      formation, in presence of oxygen, of different oxide films (passivation films) is
      correlated to titanium implant biocompatibility, resistance to corrosion and is
      responsible for implant bacteriostatic action. Surface roughness is another
      surface property of Ti-implants that, affecting implant-to-bone contact, improves
      integration. In the present study data concerning composition, surface roughness
      and biocompatibility of Ghimas implants and mini-implants undergoing sandblasting
      with Calcium Magnesium Carbonate (CaMg(CO3)2) are reported. AFM, SEM/EDX, XRD
      analyses and morpho-functional tests (MTT and ALP) were performed. Cell actin
      cytoskeletal modification (fluorescence phalloidin staining) was also observed
      with confocal laser microscopy (CLSM). Data related to surface geometry and
      chemical properties, associated with evidence of high purity of all the tested
      materials (XRD and EDX), highlighted the elevated biocompatibility of tested
      implants and mini-implants. CLSM investigation confirmed osteoblast features of
      an active cell behavior able to fit cell to chemico-mechanical stimuli present at
      the bone/implant interface and suggests an effective implant/alveolar bone
      integration in vivo.

PMID- 17211824
TI  - Modelling effectiveness of internally heterogeneous organizations in the presence
      of survey non-response: an application to the ULTRA study.
AB  - Levels of turbulence and uncertainty in family medicine practices participating
      in the ULTRA study are measured via a survey from heterogeneous viewpoints within
      each practice, including clinicians, nursing staff and office staff. In order to
      examine the effect of the average practice 'chaos' score on screening provided to
      patients, the analysis needed to account for large amounts of missing survey
      responses. Patterns of missing data included portions of missing responses within
      a job group (e.g. one out of three clinicians) to missing responses from whole
      subgroups within a practice (e.g. all three clinicians) to a whole practice of
      missing survey responses (e.g. all clinicians, nursing staff and office staff).
      The expectation-maximization (EM) algorithm, using a hierarchical model for
      covariate information, is used to handle the missing data. It was found that the
      varied patterns of missingness of survey responses among the heterogeneous
      subgroups within the practices had large effects on estimated effects of practice
      chaos on patient care.

PMID- 17211825
TI  - Probability estimation when some observations are grouped.
AB  - This paper considers the use of additional questions for decreasing survey non
      response rates and an approach for estimating a probability based on the results
      obtained. In a survey, the respondents are asked to answer an original question
      and follow-up questions, where the answers for the follow-up questions are
      grouped answers for the original question. For example, respondents are asked to
      provide an exact number of incidents, but in cases of 'Do not know' or 'Refuse'
      responses, they are subsequently asked to pick an answer from a less specific
      categorical scale. The new estimator obtains smaller variance asymptotically and
      does not depend on a distribution family. This method is applied to income
      questions in a survey regarding injury prevention and behaviours. Another
      application is survey data on intimate partner violence, where some amendments
      were applied for incorporating post-stratification weights and for using non
      random grouping. For additional illustration, an example of parameter estimation
      on artificially generated data is presented.

PMID- 17211826
TI  - Changes in albumin precursor and heat shock protein 70 expression and their
      potential role in response to corneal epithelial wound repair.
AB  - Many proteins displayed differential expression (either up- or down-regulation)
      when proteome of migrating and non-migrating epithelium was assessed using 2-DE
      and ESI-Q-TOF MS/MS. From the up-regulated set, we have identified for the first
      time a 69-kDa albumin precursor protein with four peptides sequences and 70-kDa
      heat shock protein (hsp70) with one peptide in the active phase of cell migration
      (48 h) during the healing process. Western blot analysis was used to further
      characterize these proteins at different phases (24, 48 and 72 h) of healing. An
      increase in the mRNA expression (measured using RT-PCR) in the active migration
      phase (48 h) for albumin precursor and hsp70 was also observed. Furthermore, co
      immunoprecipitation studies with anti-albumin precursor and anti-hsp70
      antibodies, followed by immunoblotting with anti-fibronectin antibody
      demonstrated a novel and biologically relevant interaction between albumin
      precursor protein and fibronectin in corneal epithelial wound healing but not
      with hsp70. The increased gene and protein expression of albumin and hsp70 during
      the active phase of cell migration (48 h) in the corneal epithelium suggests
      their possible role in corneal wound healing. These findings may have broader
      implications for developing therapeutic strategies for treating wound healing
      disorders.

PMID- 17211827
TI  - Insight into the host-parasite interplay by proteomic study of host proteins
      copurified with the human parasite, Schistosoma japonicum.
AB  - The tegument proteins of schistosome have attracted the most attention in studies
      of host-parasite interplay, while the host proteins acting at the host-parasite
      interface remained largely elusive. Here, we undertook a high-throughput
      proteomic approach to characterize the schistosome-adsorbed host proteins. Fifty
      five distinct host proteins were confidently identified in S. japonicum samples,
      including cercaria, schistosomula, adults, eggs, and miracidia, together with
      tegument and eggshell preparations, of which 23 and 38 host proteins were
      identified in adult worms and eggs, respectively. Among the schistosome-adsorbed
      host proteins, host neutrophil elastases were found in the granuloma initiated by
      schistosome egg deposition, implying that the host innate immune molecules could
      participate in the granuloma formation for fighting against schistosome invasion,
      except for the adaptive immune system. In addition, some host proteins, such as
      proteinase inhibitor and superoxide dismutase, might be utilized by schistosome
      to counteract or attenuate the host attacks. These parasite-adsorbed host
      proteins will provide new insights into the host immune responses against
      schistosome infection, the evasive behavior of the adult worms, and the granuloma
      formation, which could render an in-depth understanding for the host-parasite
      interplay.

PMID- 17211828
TI  - Influence of Ki-ras-driven oncogenic transformation on the protein network of
      murine fibroblasts.
AB  - Ki-ras gene mutations that specifically occur in codons 12, 13 and 61 are
      involved in the carcinogenesis of acute myeloid leukemia, melanoma and different
      carcinomas. In order to define potential mutation-specific therapeutic targets,
      stable transfectants of NIH3T3 cells carrying different Ki-ras4B gene mutations
      were generated. Wild type Ki-ras transformants, mock transfectants and parental
      cells served as controls. These in vitro model systems were systematically
      analyzed for their protein expression pattern using two-dimensional gel
      electrophoresis followed by mass spectrometry and/or protein sequencing. Using
      this approach, a number of target molecules that are differentially but
      coordinately expressed in the ras transfectants were identified next to other
      proteins that exhibit a distinct regulation pattern in the different cell lines
      analyzed. The differentially expressed proteins predominantly belong to the
      families of cytoskeletal proteins, heat shock proteins, annexins, metabolic
      enzymes and oxidoreductases. Their validation was assessed by real-time
      quantitative RT-PCR and/or Western blot analysis. Our results suggest that the Ki
      ras-transformed cells represent a powerful tool to study Ki-ras gene mutation
      driven protein expression profiles. In addition, this approach allows the
      discovery of ras-associated cellular mechanisms, which might lead to the
      identification of physiological targets for pharmacological interventions of the
      treatment of Ki-ras-associated human tumors.

PMID- 17211829
TI  - Proteome analysis of human macrophages reveals the upregulation of manganese
      containing superoxide dismutase after toll-like receptor activation.
AB  - Macrophages are essential for the development of innate immune responses against
      a variety of infectious factors. They detect invading pathogens via their pattern
      recognition receptors such as toll-like receptors (TLRs). TLR7/8 recognizes ssRNA
      from various viruses. In the present study, we have used 2-DE gel-based
      proteomics to find novel TLR7/8 target proteins in human monocyte-derived
      macrophages in order to improve our understanding of the virus recognition by
      this TLR. A total of 27 protein spots were found to be reproducibly
      differentially expressed between control and TLR7/8 activated 2-DE gel pairs, 18
      spots being more than two-fold upregulated and nine spots being at least two-fold
      downregulated. Several proteins involved in defense against toxic superoxide (O2
      ) and other reactive oxygen species, such as manganese-containing superoxide
      dismutase (SOD2), glutathione peroxidase, and peroxiredoxins 1 and 6 were highly
      upregulated after TLR7/8 activation. Western blot analysis showed that activation
      of macrophages with TLR2, TLR3, TLR4, and TLR7/8 ligands also strongly
      upregulated SOD2 protein expression. In conclusion, our results show that the
      activation of pattern recognition receptors of the innate immune system results
      in strong upregulation of SOD2 gene expression suggesting that SOD2 protects
      macrophages from oxidative stress during microbial infection.

PMID- 17211830
TI  - Predicting peptides bound to I-Ag7 class II histocompatibility molecules using a
      novel expectation-maximization alignment algorithm.
AB  - The useful structural features of class II MHC molecules are rarely integrated
      into T-cell epitope predictions. We propose an approach that applies a novel
      expectation-maximization algorithm to align the naturally processed peptides
      selected by the class II MHC I-A(g7) molecule - focusing on the five MHC-specific
      anchor positions. Based on the alignment profile, log of odds (LOD) scores
      supplemented with the Laplace plus-one pseudocounts method are applied to
      identify the potential T-cell epitopes. In addition, an innovative computational
      concept of hindering residues using statistical and structural information is
      developed to refine the prediction. Performance analysis by receiver operating
      characteristics statistics and the experimental validation of the LOD scores
      demonstrate the accuracy of our predictive model. Furthermore, our model
      successfully predicts T-cell epitopes of hen egg-white lysozyme protein antigen.
      Our study provides a framework for predicting T-cell epitopes in class II MHC
      molecules.

PMID- 17211831
TI  - Translational and transcriptional analysis of Sulfolobus solfataricus P2 to
      provide insights into alcohol and ketone utilisation.
AB  - The potential of Sulfolobus solfataricus P2 for alcohol or ketone bioconversion
      was explored in this study. S. solfataricus was grown in different concentrations
      (0.1-0.8% w/v) of alcohols or ketones (ethanol, iso-propanol, n-propanol,
      acetone, phenol and hexanol) in the presence of 0.4% w/v glucose. Consequently,
      the addition of these alcohols or ketones into the growth media had an inhibitory
      effect on biomass production, whereby lag times increased and specific growth
      rates decreased when compared to a glucose control. Complete glucose utilisation
      was observed in all cultures, although slower rates of glucose consumption were
      observed in experimental cultures (average of 14.9 mg/L/h compared to 18.9 mg/L/h
      in the control). On the other hand, incomplete solvent utilisation was observed,
      with the highest solvent consumption being approximately 51% of the initial
      concentration in acetone cultures. Translational responses of S. solfataricus
      towards these alcohols or ketones were then investigated using the isobaric tags
      for relative and absolute quantitation (iTRAQ) technique. The majority (>80%) of
      proteins identified and quantified showed no discernable changes in regulation
      compared to the control. These results, along with those obtained from
      transcriptional analysis of key genes involved within this catabolic process
      using quantitative RT-PCR and metabolite analysis, demonstrate successful alcohol
      or ketone conversion in S. solfataricus.

PMID- 17211832
TI  - A combined dataset of human cerebrospinal fluid proteins identified by multi
      dimensional chromatography and tandem mass spectrometry.
AB  - Human cerebrospinal fluid (CSF) is an important source for studying protein
      biomarkers of age-related neurodegenerative diseases. Before characterizing
      biomarkers unique to each disease, it is necessary to categorize CSF proteins
      systematically and extensively. However, the enormous complexity, great dynamic
      range of protein concentrations, and tremendous protein heterogeneity due to post
      translational modification of CSF create significant challenges to the existing
      proteomics technologies for an in-depth, nonbiased profiling of the human CSF
      proteome. To circumvent these difficulties, in the last few years, we have
      utilized several different separation methodologies and mass spectrometric
      platforms that greatly enhanced the identification coverage and the depth of
      protein profiling of CSF to characterize CSF proteome. In total, 2594 proteins
      were identified in well-characterized pooled human CSF samples using stringent
      proteomics criteria. This report summarizes our efforts to comprehensively
      characterize the human CSF proteome to date.

PMID- 17211833
TI  - Simple proteomic checks for detecting noncoding RNA.
AB  - Proper validation can accelerate sequence-based discovery of proteins and protein
      coding genes. Databases currently contain a backlog of experimentally unverified
      gene models and tentative assignments of observed transcripts to coding or
      noncoding RNA. We present and apply a general principle, founded on base
      composition and the genetic code and validated here by bulk 2-D gels, that can
      improve the reliability of such classifications and of the algorithms or
      pipelines that lead to them.

PMID- 17211834
TI  - Oct-4, Rex-1, and Gata-4 expression in human MSC increase the differentiation
      efficiency but not hTERT expression.
AB  - Micro-environment seems to exert an important influence on human mesenchymal stem
      cell (MSC) differentiation and proliferative capacity in bone marrow as well as
      in culture ex vivo. Oct-4, Rex-1, and TERT genes are well-known for the
      maintenance of pluripotentiality differentiation and the proliferative capacity
      of embryonic stem cells. Some previous data report expression of these embryonic
      factors in selected clones from bone marrow adult stem cells. Our goal was to
      study expression of Oct-4, Rex-1, and TERT in primary cultured human MSC
      according to the serum concentration. In addition, we have studied the expression
      of Gata-4 since this factor plays a key role in organogenesis. We hypothesized
      that low serum concentration with appropriate growth factors may induce an
      undifferentiated status with a re-expression of embryonic factors and extend
      differentiation capacity. Thus, using a defined culture medium, we report on the
      increased expression of Oct-4, Rex-1, and Gata-4 in human MSC. We have correlated
      this expression to an increase in differentiation efficiency towards osteogenic
      and adipogenic phenotypes. Our data suggest that the culture medium used permits
      the emergence of adult stem cells with a high differentiation capacity and
      expression of embryonic factors. These cells may have important implications for
      cell therapy.

PMID- 17211835
TI  - Pravastatin induces thrombomodulin expression in TNFalpha-treated human aortic
      endothelial cells by inhibiting Rac1 and Cdc42 translocation and activity.
AB  - Expression of functionally active thrombomodulin (TM) on the luminal surface of
      endothelial cells is critical for vascular thromboresistance. The 3-hydroxyl-3
      methyl coenzyme A reductase inhibitor, pravastatin, can protect the vasculature
      in a manner that is independent of its lipid-lowering activity. We examined the
      effect of pravastatin on TM expression by human aortic endothelial cells (HAECs)
      with subsequent tumor necrosis factor alpha (TNFalpha) stimulation and
      investigated the signaling pathways involved. TNFalpha treatment attenuated TM
      expression in HAECs in a time-dependent manner. Pravastatin upregulated TM levels
      in TNFalpha-treated HAECs. Specific inhibition of geranylgeranyltransferase-I or
      the Rho family by GGTI-286 or TcdB, respectively, enhanced TM expression in
      TNFalpha-treated HAECs, whereas MAP kinase inhibitors, inactivation of Rho by
      Clostridium botulinum C3 exoenzyme, or the Rho kinase inhibitor, Y-27632, had no
      effect. In TNFalpha-treated HAECs, pravastatin inhibited Rac1 and Cdc42
      activation and their translocation to the cell membrane. Blocking the
      transcriptional activation of NF-kappaB prevented the TNFalpha-induced
      downregulation of TM. The pravastatin-induced increase in TM expression in
      TNFalpha-treated HAECs was mediated through inhibition of NF-kappaB activation.
      Pravastatin regulates TM expression by inhibiting the activation of the Rho
      family proteins, Rac1 and Cdc42, and the transcription factor, NF-kappaB. The
      increase in endothelial TM activity in response to pravastatin constitutes a
      novel pleiotropic (nonlipid-related) effect of this commonly used compound and
      may be of clinical significance in disorders in which deficient endothelial TM
      plays a pathophysiological role.

PMID- 17211836
TI  - Interleukin-1beta upregulates Na+-K+-2Cl- cotransporter in human middle ear
      epithelia.
AB  - Disruption of periciliary fluid homeostasis is the main pathogenesis of otitis
      media with effusion (OME), one of the most common childhood diseases. Although
      the underlying molecular mechanisms are unclear, it has been suggested that the
      altered functions of ion channels and transporters are involved in the fluid
      collection of middle ear cavity of OME patients. In the present study, we
      analyzed the effects of a major cytokine interleukin (IL)-1beta, which was known
      to be involved in the pathogenesis of OME, on Na(+)-K(+)-2Cl(-) cotransporter
      (NKCC) in human middle ear cells. Intracellular pH (pH(i)) was measured in
      primary cultures of normal human middle ear epithelial (NHMEE) cells using a
      double perfusion chamber, which enabled us to analyze the membrane-specific
      transporter activities. NKCC activities were estimated by the pH(i) reduction due
      to bumetanide-sensitive intracellular uptake of NH(4) (+). In NHMEE cells, NKCC
      activities were observed only in the basolateral membrane, and immunoblotting
      using specific antibodies revealed the expression of NKCC1. Interestingly, IL
      1beta treatments augmented the basolateral NKCC activities and increased NKCC1
      expression. In addition, IL-1beta treatments stimulated bumetanide-sensitive
      fluid transport across the NHMEE cell monolayers. Furthermore, an elevated NKCC1
      expression was observed in middle ear cells from OME patients when compared to
      those from control individuals. The above results provide in vitro and in vivo
      evidence that the inflammatory cytokine IL-1beta upregulates NKCC1 in middle ear
      epithelial cells, which would be one of the important underlying mechanisms of
      excess fluid collection in OME patients.

PMID- 17211837
TI  - A likelihood approach to estimating sensitivity and specificity for binocular
      data: application in ophthalmology.
AB  - Binocular data typically arise in ophthalmology where pairs of eyes are
      evaluated, through some diagnostic procedure, for the presence of certain
      diseases or pathologies. Treating eyes as independent and adopting the usual
      approach in estimating the sensitivity and specificity of a diagnostic test
      ignores the correlation between eyes. This may consequently yield incorrect
      estimates, especially of the standard errors. The paper proposes a likelihood
      based method of accounting for the correlations between eyes and estimating
      sensitivity and specificity using a model for binocular or paired binary
      outcomes. Estimation of model parameters via maximum likelihood is outlined and
      approximate tests are provided. The efficiency of the estimates is assessed in a
      simulation study. An extension of the methodology to the case of several
      diagnostic tests, or the same test measured on several occasions, which arises in
      multi-reader studies, is given. A further extension to the case of multiple
      diseases is outlined as well. Data from a study on diabetic retinopathy are
      analysed to illustrate the methodology.

PMID- 17211839
TI  - Comparison of fresh and predegenerated muscle-vein-combined guides for the repair
      of rat median nerve.
AB  - Over the last 10 years, we have investigated a particular type of bioengineered
      nerve guide, the muscle-vein-combined tube, which is made by filling a vein with
      skeletal muscle. In our previous studies we have always used fresh skeletal
      muscle to fill vein conduits. In the present study we compared the use of fresh
      and predegenerated (freeze-thawed) skeletal muscle for muscle-vein-combined nerve
      guides. In this study, a 10-mm-long rat median nerve defect was repaired using
      either type of nerve guide. The samples were analyzed 5 and 30 days after surgery
      by light and electron microscopy. In addition, reverse transcription polymerase
      chain reaction (RT-PCR) was carried out to investigate the expression of mRNAs
      coding for glial markers, as well as glial growth factor (NRG1) and its receptors
      (erbB2 and erbB3). Results showed differences between the two types of nerve
      guides at postoperative day 5; however, no difference was detected at day 30
      suggesting that both types of tissue-engineered conduit are effective for
      repairing peripheral nerve defects in this experimental model.

PMID- 17211838
TI  - Fibrosis and cancer: do myofibroblasts come also from epithelial cells via EMT?
AB  - Myofibroblasts produce and modify the extracellular matrix (ECM), secrete
      angiogenic and pro-inflammatory factors, and stimulate epithelial cell
      proliferation and invasion. Myofibroblasts are normally induced transiently
      during wound healing, but inappropriate induction of myofibroblasts causes organ
      fibrosis, which greatly enhances the risk of subsequent cancer development. As
      myofibroblasts are also found in the reactive tumor stroma, the processes
      involved in their development and activation are an area of active investigation.
      Emerging evidence suggests that a major source of fibrosis- and tumor-associated
      myofibroblasts is through transdifferentiation from non-malignant epithelial or
      epithelial-derived carcinoma cells through epithelial-mesenchymal transition
      (EMT). This review will focus on the role of EMT in fibrosis, considered in the
      context of recent studies showing that exposure of epithelial cells to matrix
      metalloproteinases (MMPs) can lead to increased levels of cellular reactive
      oxygen species (ROS) that stimulate transdifferentiation to myofibroblast-like
      cells. As deregulated MMP expression and increased cellular ROS are
      characteristic of both fibrosis and malignancy, these studies suggest that
      increased MMP expression may stimulate fibrosis, tumorigenesis, and tumor
      progression by inducing a specialized EMT in which epithelial cells
      transdifferentiate into activated myofibroblasts. This connection provides a new
      perspective on the development of the fibrosis and tumor microenvironments.

PMID- 17211840
TI  - Use of adjuvant radiotherapy at hospitals with and without on-site radiation
      services.
AB  - BACKGROUND: In many areas of health care, whether patients receive specific
      medical interventions often is influenced heavily by the local availability of
      resources for delivering those services. However, relations between resource
      availability and utilization are relatively unexplored in cancer care, including
      perioperative adjuvant therapy. METHODS: The authors studied associations between
      the on-site availability of radiation services and the use of adjuvant
      radiotherapy using the national, linked Surveillance, Epidemiology, and End
      Results-Medicare database (from 1992 to 2002). They examined 1 cancer for which
      the effectiveness of adjuvant radiotherapy was well established in randomized
      clinical trials (rectal cancer) and another cancer for which it was not
      (pancreatic cancer) (N = 10,198). The availability of on-site radiation services
      at the hospital where surgery was performed was assessed by using data from the
      American Hospital Association. In comparing rates of adjuvant radiotherapy,
      analyses were adjusted for both patient characteristics and other hospital
      attributes. RESULTS: For rectal cancer, the use of adjuvant radiotherapy was
      similar in patients who underwent surgery at centers with and without on-site
      radiation services (29% vs 29%, respectively). Among patients with pancreatic
      cancer, however, those who underwent surgery at hospitals with on-site radiation
      services were twice as likely to receive radiotherapy than patients who underwent
      surgery at hospitals without such services (43% vs 26%, respectively; adjusted
      odds ratio, 2.1; 95% confidence interval, 1.4-3.2). Adjusting for other factors,
      the groups had similar survival rates for each cancer. CONCLUSIONS: The
      availability of on-site radiation services significantly increased the likelihood
      that patients would receive radiotherapy, at least for cancers for which the
      effectiveness of such therapy was not well established.

PMID- 17211841
TI  - Purtscher-like retinopathy as an initial presentation of a thrombotic
      microangiopathy associated with antineoplastic therapy.
AB  - We describe the case of a 31-year-old female with Hodgkin's lymphoma who
      developed renal and retinal thrombotic microangiopathy (TM) months after
      autologous bone marrow transplantation. Presenting symptoms were ocular and
      examination findings were consistent with a Purtscher-like retinopathy. This case
      demonstrates that patients being treated with antineoplastic therapy who develop
      TM should have an ocular examination for Purtscher retinopathy. The visual
      prognosis of Purtscher retinopathy is guarded.

PMID- 17211842
TI  - Biclonal low grade B-cell lymphoma confirmed by both flow cytometry and
      karyotypic analysis, in spite of a normal kappa/lambda Ig light chain ratio.
AB  - Composite low grade lymphoma with two subpopulations in a same site is uncommon.
      We herewith report the case of an 80-year-old woman who presented with isolated
      bilateral dacryoadenomegaly. Pathological examination of an incisional biopsy of
      her right lacrimal gland was consistent with a marginal zone lymphoma. Flow
      cytometry immunophenotyping showed two distinct clonal B-cell populations
      expressing sIg D lambda or sIg M kappa restriction in the lacrimal gland, blood,
      and bone marrow. Both B-cells populations were sorted from peripheral blood for
      molecular biology investigations and comparison with molecular data performed on
      tumor and bone marrow cells. IgH PCR performed on purified blood populations
      disclosed two monoclonal peaks: 98 bp-sized peak in the sIg M kappa and a 107 bp
      in the sIg D lambda clones, respectively. The lacrimal gland tumor expressed
      mainly sIg M kappa population, and showed a major 98 bp-sized peak coexisting
      with a very minor 107 bp peak. Cytogenetic studies showed a 46, XX,del (7)
      (q22q32) karyotype. Bone marrow examination at diagnosis revealed the same B-cell
      clones distribution than the one observed in blood with a dominant sIg D lambda
      population, a Genescan profile showing a major peak of 107 bp and a minor peak of
      98 bp. Chromosomal analysis disclosed a 46,XX,del (10) (?p14) karyotype without
      detectable 7q deletion. To our knowledge, this observation represents the first
      reported case of biclonal low grade lymphoma hidden behind a normal classical
      kappa/lambda Ig light chain ratio in blood, but clearly demonstrated by the
      combination of three ancillary techniques (flow cytometry both analytical and
      cell sorting, molecular biology, and cytogenetics) and analysis of different
      tissues (i.e., in this case, lacrimal gland biopsy, blood, and bone marrow).

PMID- 17211843
TI  - In vitro reactivity of factor VIII inhibitors with von Willebrand factor in
      different commercial factor VIII concentrates.
AB  - A relevant aspect in the treatment of patients with hemophilia A (HA) presenting
      inhibitor against factor VIII (FVIII) is the different antigenicity of FVIII used
      for replacement therapy. The aim of the study was to assess the effect of
      different products, with variable von Willebrand factor (vWF) concentration, in
      preventing the binding of inhibitor to FVIII. The reactivity of inhibitors from
      plasma of 18 patients with HA versus three commercial concentrates containing
      different amounts of vWF was compared. The results show that increasing amounts
      of vWF might have a protective effect on the transfused FVIII inactivation.

PMID- 17211844
TI  - Hb Indianapolis [beta112 (G14) Cys-->Arg] as the probable cause of moderate
      hemolytic anemia and renal damage in a Brazilian patient.
AB  - Hemoglobin (Hb) Indianapolis [beta112 (G14) Cys-->Arg] is a rare and slightly
      unstable beta-globin variant. All carriers described to date were clinically
      normal with only mild reticulocytosis. We report here a case of a Brazilian
      patient in whom hemolytic anemia and acute renal failure were probably caused by
      the presence of this variant.

PMID- 17211845
TI  - Mixed chimerism and graft failure following conditioning with the fludarabine and
      cyclophosphamide nonablative regimen; conversion to full donor chimerism.
AB  - Twenty-one patients with hematologic malignancies were treated with the
      fludarabine (120-125 mg/m(2)) and cyclophosphamide (120 mg/kg) nonmyeloablative
      conditioning regimen. Graft versus host disease (GVHD) and graft rejection
      prophylaxis was with tacrolimus and mycophenolate mofetil. Thirteen of the 21
      patients (62%) had mixed chimerism (< or = 90% donor cells) at day 60 and 11
      (52%) of these patients had mixed chimerism which persisted until day 100.
      Immunosuppression was discontinued in 12 of 13 patients and two of them converted
      to full chimerism by day 100. Eight patients received a donor lymphocyte infusion
      (DLI) and five of them converted to full donor chimerism with DLI alone. Two
      patients were given GM-CSF in addition to a DLI with conversion to full donor
      chimerism. Three patients (14%) had graft failure requiring a second transplant
      using fludarabine (125 mg/m(2)) and melphalan (140 mg/m(2)). With a median
      followup of 2.8 years, 15 patients are alive - one with disease and 14 with no
      disease. Two patients died of acute GVHD, one of chronic GVHD, and three due to
      progressive disease. We conclude that the nonmyeloablative
      fludarabine/cyclophosphamide regimen results in a significant incidence of mixed
      chimerism and graft rejection but is well tolerated. We suggest a more intense
      regimen, such as fludarabine and melphalan, be used in patients with a high risk
      of early disease progression to establish early engraftment and graft versus
      tumor effect.

PMID- 17211846
TI  - Hodgkin's disease complicated by cardiomyopathy in two young adults.

PMID- 17211847
TI  - Frequency of intron 1 and 22 inversions of Factor VIII gene in Mexican patients
      with severe hemophilia A.
AB  - Hemophilia A (HA) is one of the most common inherited bleeding disorders caused
      by FVIII gene mutations. Inversion of intron 22 (inv22) originates 50% of cases
      of severe HA and is a major risk factor for inhibitor development. Inversion of
      intron 1 (inv1) has been reported to occur in 2-3% of severe HA patients. We
      studied both inversions to determine their frequencies in Mexican patients with
      severe HA and to compare these data with other HA populations. The inv22 was
      evaluated as a risk factor for FVIII inhibitor development in severe HA patients.
      We studied 44 patients from 31 severe HA families for the detection of inv22 and
      94 patients from 65 families to detect inv1. We used the subcycling long-distance
      PCR to detect inv22 and rapid PCR in duplex reactions to detect inv1. We found a
      frequency of 45% for the inv22 and no inv1-positive patients (0%). These
      frequencies were not statistically different from other populations, although
      haplotype analyses of FVIII gene and telomeric regions should be incorporated to
      explore population-specific variation of inv1 frequencies. Inv22-positive
      patients showed 1.88X higher risk for developing inhibitors with respect to
      patients carrying other severe mutations; however, this OR value was not
      significant. Our findings confirm inv22 as a hot-spot for severe HA and evidence
      the low frequency of inv1 in a Mexican population. The non-significant risk for
      developing inhibitors among inv22-positive patients agrees with the variety of
      genetic and non-genetic factors involved in such a complication.

PMID- 17211848
TI  - Evidence for linkage of red blood cell size and count: genome-wide scans in the
      Framingham Heart Study.
AB  - Red blood cell (RBC) count and size are major criteria for evaluating anemia and
      related hematology disease diagnoses. While environmental factors influence RBC
      count (RBCC) and size, mean corpuscular volume (MCV), and mean corpuscular
      hemoglobin (MCH), studies have indicated that each of these measures has a
      substantial genetic component. So far, no linkage analysis or genome scan has
      been reported. We carried out 10 cM genome-wide scans on RBCC, MCV, and MCH in a
      community-based Caucasian cohort, the Framingham Heart Study, using 325 pedigrees
      with 1,144 individuals genotyped and phenotyped. Using variance-component linkage
      methods, heritabilities were estimated as 56, 52, and 52% after covariate
      adjusted for RBCC, MCV, and MCH, respectively. For RBCC, we found a maximum LOD
      score of 3.2 on chromosome 19, 24 cM (7.0 Mbp). Near this region, there lie a few
      important candidate genes, including erythropoietin receptor and erythroid
      Kruppel-like factor. For linkage analyses for MCV and MCH, there were coinciding
      maximized LOD scores on chromosome 11, 9 cM (5.2 Mbp) with values of 3.8 and 3.6,
      respectively. Under the peak resides the hemoglobin beta cluster - several beta
      like genes, which are important candidates for RBC size. In subsequent analyses,
      we excluded individuals with low MCV to assess the possible influence of beta
      thalassemia carriers, and there continued to be evidence for linkage in the same
      region on chromosome 11p15 (LOD scores of 2.6 and 2.7 for MCV and MCH,
      respectively). For MCV, we also identified a new region on chromosome 6q24 with a
      LOD score of 2.9. These findings suggest that further studies are warranted to
      identify potential causal genetic variants for RBC size and count and related
      erythrocyte indices.

PMID- 17211849
TI  - Increased expression of integrin beta1 subunit enhances p21WAF1/Cip1
      transcription through the Sp1 sites and p300-mediated histone acetylation in
      human hepatocellular carcinoma cells.
AB  - Integrins, a class of membrane receptors, are major players in transmitting the
      mechanical force across the plasma membrane. We previously reported that
      overexpression of integrin beta1 subunit imposed a growth inhibitory effect on
      the hepatocellular carcinoma cell line SMMC-7721 through transcriptional
      activation of p21(WAF1/CIP1) gene. In this study, we further determined the
      molecular mechanisms underlying p21(WAF1/CIP1) expression induced by integrin
      beta1 overexpression. We report herein that overexpression of integrin beta1
      subunit upregulates p21(WAF1/Cip1) transcription through a p53-independent
      pathway. The overexpressed integrin beta1 activates the p21(WAF1/Cip1) promoter
      through the Sp1/Sp3 sites and makes more transcription factor Sp1 recruited to
      the proximal p21 promoter region. In addition, it makes the acetylation value of
      histone proteins increased across some parts of the p21(WAF1/Cip1) gene,
      especially in the promoter region. The transcriptional co-activator p300, which
      possesses intrinsic histone acetyltransferase, was found to be involved in the
      integrin beta1-mediated histone acetylation and p21 transcriptional activation.
      Therefore, these findings presented the mechanisms by which integrin beta1
      induced the elevated p21 expression in hepatic cancer cells.

PMID- 17211850
TI  - TGF-beta1 calcium signaling in osteoblasts.
AB  - Transforming growth factor-beta1 (TGF-beta1) action is known to be initiated by
      its binding to multiple cell surface receptors containing serine/threonine kinase
      domains that act to stimulate a cascade of signaling events in a variety of cell
      types. We have previously shown that TGF-beta1 and BMP-2 treatment of primary
      human osteoblasts (HOBs) enhances cell-substrate adhesion. In this report, we
      demonstrate that TGF-beta1 elicits a rapid, transient, and oscillatory rise in
      the intracellular Ca(2+) concentration, [Ca(2+)](i), that is necessary for
      enhancement of cell adhesion in HOBs but does not alter the phosphorylation state
      of Smad proteins. This rise in [Ca(2+)](i) in HOB is not observed in the absence
      of extracellular calcium or when the cells are treated with the L-type Ca(2+)
      channel blocker, nifedipine, but is stimulated upon treatment with the L-type
      Ca(2+) channel agonist, Bay K 8644, or under high K(+) conditions. The rise in
      [Ca(2+)](i) is severely attenuated after treatment of the cells with
      thapsigargin, a selective endoplasmic reticulum Ca(2+) pump inhibitor. TGF-beta1
      enhancement of HOB adhesion to tissue culture polystyrene is also inhibited in
      cells treated with nifedipine. These data suggest that intracellular Ca(2+)
      signaling is an important second messenger of the TGF-beta1 signal transduction
      pathway in osteoblast function.

PMID- 17211851
TI  - Suppressing phosphatidylcholine-specific phospholipase C and elevating ROS level,
      NADPH oxidase activity and Rb level induced neuronal differentiation in
      mesenchymal stem cells.
AB  - In the previous research, we found that D609 (tricyclodecan-9-yl-xanthogenate)
      could induce human marrow stromal cell (hMSC) differentiation to neuron-like
      cells. In this study, to understand the possible mechanism, we sequentially
      investigated the changes of phosphatidylcholine-specific phospholipase C (PC-PLC)
      activity, the expression of Rb, the intracellular reactive oxygen species (ROS)
      levels, NADPH oxidase and superoxide dismutase (SOD) activities when D609 induced
      neuronal differentiation in rat mesenchymal stem cells (MSCs). The results showed
      that D609 obviously inhibited the activity of PC-PLC when it induced neuronal
      differentiation in rat MSCs. Simultaneously, ROS level and the activity of NADPH
      oxidase increased significantly, but the MnSOD and Cu/ZnSOD activities were not
      altered. Furthermore, the level of Rb protein was evidently elevated. Our data
      suggested that PC-PLC mediated neuronal differentiation of rat MSCs by elevating
      NADPH oxidase activity, ROS level, and up-regulating the expression of Rb
      protein.

PMID- 17211852
TI  - Functions and regulation of human artemis in double strand break repair.
AB  - Cells, which lacked the activity of the nuclease Artemis, retained approximately
      10% of unrepaired double strand breaks (DSBs) at later timepoints after ionizing
      radiation. Ionizing radiation induced hyperphosphorylation of Artemis mainly by
      ATM and in ATM deficient cells to a minor extent by DNA PK. After induction of
      DSBs with modified ends by a high dose of calicheamicin gamma1, Artemis was
      phosphorylated by DNA PK. The type of calicheamicin gamma1-induced DSBs is likely
      to represent a subclass of DSBs induced by ionizing radiation. DNA PK-dependent
      phosphorylation of Artemis after treatment with DSB inducing agents increased the
      cellular retention of Artemis, maintained its interaction with DNA ends and
      activated its endonucleolytic activity. The following model is suggested: ATM
      dependent phosphorylation of Artemis after ionizing radiation could prevent DNA
      PK-dependent phosphorylation and activation of undesired endonucleolytic activity
      at DSBs, which do not require endonucleolytic processing by Artemis. The
      Artemis:DNA PK complex could be involved in the repair of DSBs, which carry
      modified ends and are refractory to repair by otherwise lesion specific enzymes
      because of the presence of an inhibitory lesion in the opposite strand.

PMID- 17211853
TI  - One- and two-stage designs for phase II window studies.
AB  - The primary goal of phase II window studies in cancer is testing new single
      agents or combination therapies for newly diagnosed patients who are less likely
      to have multiple-drug-resistant tumours than the typical phase II patients who
      have failed one or more chemotherapeutic regimens. In addition, by utilizing
      newly diagnosed patients, one can assess the responsiveness in a population more
      representative of where the phase II agent might be applied in a true phase III
      setting. In general, the outcome of a patient on a phase II window study can be
      categorized as response, stable disease, or early disease progression. Phase II
      window studies sometimes require early stopping rules for both insufficient
      response rate and excessive early progression rates. In this paper, one-stage and
      two-stage designs for phase II window studies are developed, requiring the
      monitoring of two rates. It is shown that the power function is monotone in
      response rate and early disease progression rate. Consequently, the significance
      level and power are easy to compute. Computational procedures are described and
      examples are provided. The proposed method can be applied to other studies with
      categorical outcomes.

PMID- 17211854
TI  - Fat-loaded HepG2 spheroids exhibit enhanced protection from Pro-oxidant and
      cytokine induced damage.
AB  - The mechanisms by which steatosis renders hepatocytes susceptible to damage in
      non-alcoholic steatohepatitis (NASH) are unclear although fat accumulation is
      believed to increase hepatocyte susceptibility to inflammatory cytokines and
      oxidative stress. We therefore investigated the susceptibility of steatotic,
      hepatocyte-derived cells to TNFalpha and the pro-oxidant, t-butylhydroperoxide
      (TBH). HepG2 spheroids rendered steatotic by fat-loading with 0.15 mM oleic or
      palmitic acid for 48 h and treated with TNFalpha or TBH for 18 h exhibited
      surprisingly lower levels of cytotoxicity, and increased anti-oxidant activity
      (superoxide dismutase (SOD)) compared with non fat-loaded controls. The
      protective effect of steatosis was significantly reversed by the inhibition of
      AMP-activated kinase (AMPK) since spheroids transfected with a kinase-dead
      AMPKalpha2 subunit, exhibited a significant increase in TBH-induced cytotoxicity
      when fat-loaded. In conclusion, our findings suggest that fat-loaded hepatocyte
      derived cells are surprisingly less susceptible to cytokine and pro-oxidant
      induced damage via an adaptive mechanism dependent, in part, on AMPK activity.

PMID- 17211855
TI  - Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial
      glucose and lipid metabolism in patients with type 2 diabetes mellitus: a
      prospective, randomized crossover study.
AB  - BACKGROUND: Postprandial metabolism is impaired in patients with type 2 diabetes
      (T2Dm). Two thiazolidinediones pioglitazone (PGZ) and rosiglitazone (RGZ) have
      similar effects on glycaemic control but differ in their effects on fasting
      lipids. This study investigated the effects of RGZ and PGZ on postprandial
      metabolism in a prospective, randomized crossover trial. METHODS: Seventeen
      patients with T2Dm were randomized to RGZ or PGZ for 12 weeks, with an 8-week
      wash-out period. Fasting blood samples were taken for glucose (FPG), insulin,
      HbA(1c), lipids, apolipoproteins (apo), lipoprotein (LPL) and hepatic lipase
      (HL), and cholesterol ester transfer protein (CETP) activity. A standardized
      breakfast was served and postprandial glucose, insulin, and lipid subfraction
      profiles were determined. RESULTS: RGZ and PGZ treatment resulted in a similar
      improvement in FPG, HbA(1c) and homeostasis model assessment. Fasting and
      postprandial triglyceride (TG) levels were significantly lower following PGZ
      therapy (fasting: -0.35 vs 0.44 mmol/L; p < 0.04; postprandial AUC-TG: -195.6 vs
      127.9 mmol/L/min; p < 0.02) associated with changes in VLDL-2-TG (-0.10 vs 0.21
      mmol/L; p = 0.23) and VLDL-3-TG (0.0 vs 0.34 mmol/L; p < 0.04). Fasting
      cholesterol increased with RGZ compared to PGZ (0.06 vs 0.59 mmol/L; p < 0.04),
      particularly in VLDL-2-C (-0.30 vs 0.59 mmol/L; p < 0.03) and VLDL-3-C (-0.85 vs
      2.11 mmol/L; p < 0.02). Postprandial VLDL lipid and protein content increased
      after RGZ and decreased after PGZ. Fasting apoB, apoA-I, apoC-II/C-III-ratio, and
      LPL activity did not differ. CETP activity decreased after RGZ and increased
      after PGZ (-6.2 vs 4.2 p/mol/mL/min; p < 0.002). CONCLUSIONS: Both the glitazones
      had similar effects on glucose metabolism. The additional beneficial effect of
      PGZ on lipid metabolism may be related to its effects on insulin-independent VLDL
      production and CETP activity.

PMID- 17211856
TI  - Statistical evidence for GLM regression parameters: a robust likelihood approach.
AB  - When a likelihood ratio is used to measure the strength of evidence for one
      hypothesis over another, its reliability (i.e. how often it produces misleading
      evidence) depends on the specification of the working model. When the working
      model happens to be the 'true' or 'correct' model, the probability of observing
      strong misleading evidence is low and controllable. But this is not necessarily
      the case when the working model is misspecified. Royall and Tsou (J. R. Stat.
      Soc., Ser. B 2003; 65:391-404) show how to adjust working models to make them
      robust to misspecification. Likelihood ratios derived from their 'robust adjusted
      likelihood' are just as reliable (asymptotically) as if the working model were
      correctly specified in the first place. In this paper, we apply and extend these
      ideas to the generalized linear model (GLM) regression setting. We provide
      several illustrations (both from simulated data and real data concerning rates of
      parasitic infection in Philippine adolescents), show how the required adjustment
      factor can be obtained from standard statistical software, and draw some
      connections between this approach and the 'sandwich estimator' for robust
      standard errors of regression parameters. This substantially broadens the
      availability and the viability of likelihood methods for measuring statistical
      evidence in regression settings.

PMID- 17211857
TI  - Quantitated transcript haplotypes (QTH) of AGTR1, reduced abundance of mRNA
      haplotypes containing 1166C (rs5186:A>C), and relevance to metabolic syndrome
      traits.
AB  - The angiotensin II type 1 receptor (AGTR1) is the main target through which
      angiotensin II influences cardiovascular tone, cell growth, and fluid and
      electrolyte balance. AGTR1 polymorphism has been reported to associate with
      hypertension, myocardial infarction (MI), and metabolic traits. Here we describe
      a novel approach to quantitation of transcript haplotypes (QTH) of AGTR1. To
      determine relative allelic expression from haplotypes, within-individual-between
      allele ratiometric analyses in placental cDNA were developed for the transcribed
      SNPs rs5182:C>T (encoding p.L191) and rs5186:A>C (3'-noncoding "A1166C").
      Additionally, between-individual comparisons were made using TaqMan assays
      applied to both homozygous and heterozygous genotypes and haplotypes. In
      conjunction, linkage disequilibrium (LD) and genomic haplotype associations with
      metabolic syndrome were examined. There was no significant difference of mRNA
      level for alleles of rs5182:C>T, but allele and mRNA haplotypes carrying 1166C
      exhibited reduced abundance. The effect was much greater in CC homozygotes than
      in heterozygotes. The promoter region was confirmed to be in a separate haplotype
      block from the AGTR1 3' region containing rs5182:C>T and rs5186:A>C. Metabolic
      syndrome trait associations were strongest for the 3' block generally and for the
      C allele of rs5186:A>C specifically. All effects were much more prominent in
      homozygotes, possibly reflecting interallelic interaction through feedback loops
      of mRNA regulation. Differential abundance of AGTR1 mRNA haplotypes may mediate
      clinical phenotypic observations of the AGTR1 genotype.

PMID- 17211858
TI  - Three arginine to cysteine substitutions in the pro-alpha (I)-collagen chain
      cause Ehlers-Danlos syndrome with a propensity to arterial rupture in early
      adulthood.
AB  - Mutations in the COL1A1 and COL1A2 genes, encoding the proalpha1 and 2 chains of
      type I collagen, cause osteogenesis imperfecta (OI) or Ehlers-Danlos syndrome
      (EDS) arthrochalasis type. Although the majority of missense mutations in the
      collagen type I triple helix affect glycine residues in the Gly-Xaa-Yaa repeat,
      few nonglycine substitutions have been reported. Two arginine-to-cysteine
      substitutions in the alpha1(I)-collagen chain are associated with classic EDS
      [R134C (p.R312C)] or autosomal dominant Caffey disease with mild EDS features
      [R836C (p.R1014C)]. Here we show alpha1(I) R-to-C substitutions in three
      unrelated patients who developed iliac or femoral dissection in early adulthood.
      In addition, manifestations of classic EDS in Patient 1 [c.1053C>T; R134C
      (p.R312C); X-position] or osteopenia in Patients 2 [c.1839C>T; R396C (p.R574C); Y
      position] and 3 [c.3396C>T; R915C (p.R1093C); Y-position] are seen. Dermal
      fibroblasts from the patients produced disulfide-bonded alpha1(I)-dimers in
      approximately 20% of type I collagen, which were efficiently secreted into the
      medium in case of the R396C and R915C substitution. Theoretical stability
      calculations of the collagen type I heterotrimer and thermal denaturation curves
      of monomeric mutant alpha1(I)-collagen chains showed minor destabilization of the
      collagen helix. However, dimers were shown to be highly unstable. The R134C and
      R396C caused delayed procollagen processing by N-proteinase. Ultrastructural
      findings showed collagen fibrils with variable diameter and irregular
      interfibrillar spaces, suggesting disturbed collagen fibrillogenesis. Our
      findings demonstrate that R-to-C substitutions in the alpha1(I) chain may result
      in a phenotype with propensity to arterial rupture in early adulthood. This
      broadens the phenotypic range of nonglycine substitutions in collagen type I and
      has important implications for genetic counseling and follow-up of patients
      carrying this type of mutation.

PMID- 17211859
TI  - Reproductive factors and family history of breast cancer in relation to plasma
      prolactin levels in premenopausal and postmenopausal women.
AB  - Many reproductive factors are associated with breast cancer risk, potentially
      through a hormonal pathway. The peptide hormone prolactin is essential in mammary
      development and lactation and may be a link between risk factors and breast
      cancer. While higher prolactin levels are associated with increased breast cancer
      risk, few determinants of prolactin levels are known. We conducted a cross
      sectional analysis among 1,089 premenopausal and 1,311 postmenopausal women
      within the Nurses' Health Study (NHS) and the NHS II to examine the associations
      of reproductive factors, benign breast disease and family history of breast
      cancer with plasma prolactin levels. Parous women had significantly lower
      prolactin levels than nulliparous women (parous vs. nulliparous multivariate
      adjusted geometric means = 14.1 ng/mL vs. 16.6 ng/mL, p<0.001 for premenopausal
      and 9.1 vs. 10.1, p=0.04 for postmenopausal women), although levels did not
      decrease with increasing number of children for either premenopausal (p-trend =
      0.23) or postmenopausal (p-trend = 0.07) parous women. Age at first birth was not
      associated with prolactin levels. The reduction in prolactin levels among parous
      premenopausal women appeared to attenuate with increasing time since first birth,
      but the trend was not statistically significant (p-trend = 0.12). Age at
      menarche, duration of lactation and benign breast disease were not associated
      with prolactin levels. Family history of breast cancer was associated with
      significantly higher prolactin levels when compared with no family history among
      premenopausal (15.9 ng/mL vs. 14.3 ng/mL, p=0.04) but not postmenopausal (p=0.73)
      women. In conclusion, the associations of parity and family history with breast
      cancer risk may be mediated, at least in part, by prolactin levels.

PMID- 17211860
TI  - A prospective cohort study of red wine consumption and risk of prostate cancer.
AB  - In light of recent, strong inverse findings between lifetime red wine consumption
      and prostate cancer among younger men, we revisited our previous cohort analysis
      to more thoroughly investigate red wine consumption and prostate cancer in the
      Health Professionals Follow-up Study (HPFS). In 1986, HPFS participants reported
      their average consumption of red wine, white wine, beer and liquor during the
      past year, and their change in alcohol consumption over the prior 10 years.
      Prostate cancer diagnoses were ascertained on each biennial questionnaire and
      confirmed by medical record review. Between 1986 and 2002, 3,348 cases of
      prostate cancer were diagnosed among 45,433 eligible participants. Using men who
      did not consume red wine as the reference, no linear trend was observed between
      red wine consumption and prostate cancer in the full analytic cohort (p-trend =
      0.57). Among men with unchanged alcohol consumption in the prior 10 years, and
      those additionally <65 years of age, slightly lower risks were observed for men
      who consumed <or=4 glasses of red wine/week, whereas null or slight increased
      risks were observed for men who consumed >4 glasses/week, resulting in a lack of
      linear trend. These findings suggest that red wine does not contribute
      appreciably to the etiology of prostate cancer.

PMID- 17211861
TI  - Randomized phase II trial of two different schedules of docetaxel plus cisplatin
      as first-line therapy in advanced nonsmall cell lung cancer.
AB  - BACKGROUND: There is increasing interest in the use of a weekly administration of
      docetaxel as a way of reducing its hematologic toxicity. The purpose of the
      current randomized study was to evaluate the toxicity and efficacy of docetaxel
      plus cisplatin combination on 2 schedules in patients with previously untreated,
      advanced nonsmall-cell lung cancer (NSCLC). METHODS: Consenting patients with
      advanced NSCLC were randomized to receive first-line chemotherapy with cisplatin
      75 mg/m(2) on Day 1, plus 3-weekly (75 mg/m(2) on Day 1) or weekly (35 mg/m(2) on
      Days 1, 8, and 15 of a 4-week cycle) docetaxel, for up to 6 cycles. RESULTS: Of
      86 patients accrued, 41 patients were treated with 3-weekly and 43 with weekly
      docetaxel plus cisplatin. The most frequent grade 3/4 toxicity in the 3-weekly
      arm was neutropenia (56% of patients). In those receiving the weekly regimen, the
      frequent grade 3/4 toxicities were fatigue (44%) and nausea/vomiting (35%). The
      overall response rate was 40% with the 3-weekly and 39% with the weekly arm (P =
      .74). The median progression-free survival was 4.3 months in the 3-weekly arm and
      3.9 months in the weekly arm (P = .08) and the median survival was 10.3 and 10.0
      months, respectively (P = .76). Quality of life data showed no relevant
      difference between the arms. CONCLUSIONS: The weekly schedule of docetaxel plus
      cisplatin combination as first-line chemotherapy for advanced NSCLC, while
      feasible, has no clear advantage over the standard 3-weekly regimen.

PMID- 17211862
TI  - Clinical and endoscopic factors predict higher pathologic grades of Barrett
      dysplasia.
AB  - BACKGROUND: Barrett esophagus is highly prevalent in the Western world; however,
      only a minority of affected individuals progress to esophageal adenocarcinoma.
      Whereas many studies have examined risk factors for development of Barrett
      metaplasia, few data are available on risk factors for progression to neoplasia.
      Identifying simple, reliable, clinical, and endoscopic predictors of high-grade
      dysplasia and adenocarcinoma would be helpful for risk stratification in
      screening and surveillance programs. METHODS: Clinical, endoscopic, and
      histologic data were reviewed for patients with a new Barrett diagnosis between
      2002 and 2005. Patients were classified, by an expert gastrointestinal
      pathologist, as having intestinal metaplasia, indefinite-for-dysplasia, low-grade
      dysplasia, high-grade dysplasia, and esophageal adenocarcinoma. Gender, age,
      race, ethnicity, hiatal hernia presence and size, Barrett segment length, H.
      pylori status, alcohol, smoking, proton pump inhibitor (PPI) use and duration,
      and reflux symptom duration were evaluated by logistic regression analysis for
      their association with dysplasia severity. RESULTS: In all, 109 patients (26
      women, 83 men, mean age: 58.8) were newly diagnosed with Barrett metaplasia (n =
      39), indefinite/low-grade dysplasia (n = 35), and high-grade dysplasia/esophageal
      adenocarcinoma (n = 35) over a 3-year period. On logistic regression analysis,
      duration of reflux symptoms for >or=20 years (odds ratio [OR]: 5.66, P = .012),
      longer Barrett segment length (OR for 3-6 cm vs. <3 cm: 9.05, P < .0001; OR for
      >or=6 cm: 8.374, P < .0001), hernia size >or=4 cm (OR: 10.63, P = .014), and male
      gender (OR: 4.03, P = .0019) were associated with higher pathologic grade.
      Duration of reflux symptoms and Barrett length were significant as both discrete
      and continuous variables. Absence of H. pylori (OR: 2.731, P = .060) approached
      significance in predicting dysplasia severity. In bivariate models, gender and
      Barrett length (continuous form) were significantly associated with grade when
      considered together (OR: 2.52, P = .0490 and OR: 1.30, P < .0001), as were gender
      and hernia size >4 cm (OR: 4.64, P = .0049 and OR: 12.18, P = .0197).
      CONCLUSIONS: Male gender, longstanding gastroesophageal reflux disease, hiatal
      hernia size, and segment length are strongly associated with higher grades of
      dysplasia at index diagnosis. These factors along with H. pylori status warrant
      further prospective evaluation as predictors of risk for development of high
      grade dysplasia and esophageal adenocarcinoma.

PMID- 17211863
TI  - Prospective study of adiposity and weight change in relation to prostate cancer
      incidence and mortality.
AB  - BACKGROUND: Adiposity has been linked inconsistently with prostate cancer, and
      few studies have evaluated whether such associations vary by disease
      aggressiveness. METHODS: The authors prospectively examined body mass index (BMI)
      and adult weight change in relation to prostate cancer incidence and mortality in
      287,760 men ages 50 years to 71 years at enrollment (1995-1996) in the National
      Institutes of Health-AARP Diet and Health Study. At baseline, participants
      completed questionnaires regarding height, weight, and cancer screening
      practices, including digital rectal examinations and prostate-specific antigen
      tests. Cox regression analysis was used to calculate relative risks (RR) and 95%
      confidence intervals (95% CIs). RESULTS: In total, 9986 incident prostate cancers
      were identified during 5 years of follow-up, and 173 prostate cancer deaths were
      ascertained during 6 years of follow-up. In multivariate models, higher baseline
      BMI was associated with significantly reduced total prostate cancer incidence,
      largely because of the relationship with localized tumors (for men in the highest
      BMI category [>or=40 kg/m(2)] vs men in the lowest BMI category [<25 kg/m(2)]:
      RR, 0.67; 95% CI, 0.50-0.89; P = .0006). Conversely, a significant elevation in
      prostate cancer mortality was observed at higher BMI levels (BMI <25 kg/m(2): RR,
      1.0 [referent group]; BMI 25-29.9 kg/m(2): RR, 1.25; 95% CI, 0.87-1.80; BMI 30
      34.9 kg/m(2): RR, 1.46; 95% CI, 0.92-2.33; and BMI >or=35 kg/m(2): RR, 2.12; 95%
      CI, 1.08-4.15; P = .02). Adult weight gain from age 18 years to baseline also was
      associated positively with fatal prostate cancer (P = .009), but not with
      incident disease. CONCLUSIONS: Although adiposity was not related positively to
      prostate cancer incidence, higher BMI and adult weight gain increased the risk of
      dying from prostate cancer.

PMID- 17211864
TI  - A pooled analysis of quality of life measures and adverse events data in north
      central cancer treatment group lung cancer clinical trials.
AB  - BACKGROUND: In this pooled analysis, the authors examined correlations between
      single-item and multiple-item quality of life (QOL) measures and assessed the
      agreement between clinically significant changes in QOL and patient-reported
      adverse events (AE). METHODS: Data from 6 lung cancer clinical trials that
      involved 358 patients were pooled. All trials incorporated the Uniscale and 1 of
      3 multiple-item assessments: the Functional Assessment for Cancer Therapy-Lung,
      the Lung Cancer Symptom Scale, or the Symptom Distress Scale. Spearman rank
      correlations and a Bland-Altman approach were used to assess agreement. Time-to
      event analysis was performed using the Kaplan-Meier method. RESULTS: Correlations
      between the Uniscale and multiple-item assessments were substantial (correlation
      coefficient = 0.49-0.66). At least 1 10-point decline was reported in the
      Uniscale and multiple-item assessments by 58% of patients and 39% of patients,
      respectively. At least 1 severe AE (grade >or=3) was reported in 35% of patients
      postbaseline. The percent agreement between experiencing a severe AE and a
      decline in QOL was 48% and 59% for the Uniscale and multiple-item assessments,
      respectively. The median time to the first 10-point decline in QOL for the
      Uniscale and multiple-item assessments was 67 days and 142 days, respectively,
      and the median time to the first occurrence of a severe AE was 304 days.
      CONCLUSIONS: Information gleaned from the single-item Uniscale assessment was
      comparable to that gleaned from multiple-item global measures. There was moderate
      agreement between QOL and AE. A 10-point decline in QOL occurred earlier than
      Common Toxicity Criteria AE reporting. This suggests the need for inclusion of a
      QOL instrument in lung cancer clinical trials.

PMID- 17211865
TI  - Expression of epidermal growth factor receptor in esophageal and esophagogastric
      junction adenocarcinomas: association with poor outcome.
AB  - BACKGROUND: The prognosis for patients with esophageal and esophagogastric
      junction (EGJ) adenocarcinoma remains poor, even after surgical resection.
      Pathologic assessment of depth of invasion and lymph node status are the primary
      prognostic factors in these patients. In patients with esophageal squamous cell
      carcinoma, increased epidermal growth factor receptor (EGFR) expression has been
      associated with a worse prognosis. It is not known whether EGFR plays a similar
      role in esophageal and EGJ adenocarcinomas. METHODS: To address this issue, the
      authors studied tumor specimens from 103 patients with surgically resected
      esophageal and EGJ adenocarcinomas (9 patients with stage I disease, 23 patients
      with stage II disease, 57 patients with stage III disease, and 14 patients with
      stage IV disease). The expression of EGFR was assessed by immunohistochemical
      analysis of tissue microarrays. Tumors were considered positive for EGFR
      expression when >5% of tumor cells were stained and negative when <or=5% of tumor
      cells were stained. RESULTS: EGFR was expressed in 33 of 103 adenocarcinomas
      (32%) and was correlated with higher pathologic tumor (T) classification (P =
      .02), the presence of lymph node metastasis (P = .01), and higher pathologic
      tumor, lymph node, metastasis classification (P = .02). EGFR expression also was
      correlated with shorter disease-free and overall survival in univariate analyses
      (P = .001 and P = .004, respectively), and there was a trend toward a correlation
      between EGFR expression and shorter disease-free survival in multivariate
      analyses (P = .07 and P = .08). The results demonstrated that EGFR expression in
      esophageal adenocarcinomas was correlated with advanced pathologic tumor
      classification and lymph node metastasis. EGFR expression also was correlated
      with poor disease-free and overall survival, but that correlation was not
      independent of T classification. CONCLUSIONS: The current findings suggested that
      EGFR expression correlates with poor prognostic factors and may be used to
      predict patient outcomes.

PMID- 17211866
TI  - Enhanced chemotherapy delivery by intraarterial infusion and blood-brain barrier
      disruption in the treatment of cerebral metastasis.
AB  - BACKGROUND: Cerebral metastases are clinically significant in 10% to 30% of
      patients with neoplasia. Multiple cerebral metastases are typically treated with
      palliative radiotherapy. There is no consensus on the role of enhanced
      chemotherapy delivery as an adjuvant treatment modality in this disease. In this
      report, the authors detailed their experience with intraarterial (IA)
      chemotherapy infusion with and without blood-brain barrier disruption (BBBD) in
      patients with multiple cerebral metastases. METHODS: From November 1999 to May
      2005, 38 patients with multiple cerebral metastases were enrolled in a
      prospective study. Patients were treated with IA carboplatin, except for those
      with cerebral metastases of systemic lymphoma, who were administered IA
      methotrexate. Osmotic BBBD was offered to patients without the presence of a
      significant mass effect. These regimens were coupled with intravenous etoposide
      and cyclophosphamide. Cycles were repeated every 4 weeks. RESULTS: Survival was
      calculated from study entry and radiologic response was based on MacDonald
      criteria. Kaplan-Meier estimates were generated for all subgroups. Mean and
      median survival obtained was as follows: 34 and 29.6 months for the whole group;
      33.6 and 42.3 months for ovarian carcinoma; 15.3 and 13.5 months for lung
      adenocarcinomas; 8.3 and 8.8 months for small cell lung carcinoma; 8.9 and 8.1
      months for breast carcinoma; and 24.8 and 16.3 months, respectively, for cerebral
      metastasis from systemic lymphoma. CONCLUSIONS: Even with a small number of
      patients in each subgroup, the results obtained seem promising for multiple brain
      metastasis of ovarian carcinoma, adenocarcinoma of lung, small cell lung
      carcinoma, and systemic lymphoma.

PMID- 17211867
TI  - Improved cine displacement-encoded MRI using balanced steady-state free
      precession and time-adaptive sensitivity encoding parallel imaging at 3 T.
AB  - Cine displacement-encoded MRI is a promising modality for quantifying regional
      myocardial function. However, it has two major limitations: low signal-to-noise
      ratio (SNR) and data acquisition efficiency. The purpose of this study was to
      incrementally improve the SNR and the data acquisition efficiency of cine
      displacement-encoded MRI through the combined use of balanced steady-state free
      precession (b-SSFP) imaging, 3T imaging, echo-combination image reconstruction,
      and time-adaptive sensitivity encoding (TSENSE) parallel imaging. Phantom
      experiments were performed to empirically determine the optimal excitation angle
      (alpha) and to estimate the measurement errors in the presence of 130 Hz peak-to
      peak static magnetic field (B0) variation. The optimal alpha was determined to be
      20 degrees . The intrinsic phase correction in the echo-combination effectively
      reduced the phase error, which produced small displacement errors (0.11 versus
      0.11 mm) and negligible strain errors (-0.001 versus -0.002). Six healthy
      volunteers were imaged in three short-axis levels of the heart to evaluate the
      SNR and the relative accuracy of strain calculations. Compared with the 24
      heartbeat cine echo-planar imaging acquisition, the 24-heartbeat non-accelerated
      b-SSFP acquisition yielded approximately 65% higher SNR, and the 12-heartbeat
      twofold accelerated b-SSFP acquisition yielded approximately 28% higher SNR. The
      12-heartbeat twofold accelerated b-SSFP acquisition yielded functional maps with
      spatial resolution of 3.6 x 3.6 mm, temporal resolution of 35 ms, and relatively
      high SNR (31.2 +/- 5.4 at end diastole; 19.9 +/- 3.6 at end systole; 10.3 +/- 1.1
      at late diastole; mean +/- SD). The left ventricular strain values between the
      non-accelerated and twofold accelerated b-SSFP acquisitions correlated strongly
      (slope = 0.99; bias = 0.00; R2 = 0.91) and were in excellent agreement. The
      combined implementation of b-SSFP imaging, 3T imaging, echo-combination image
      reconstruction, and TSENSE parallel imaging can be used to incrementally improve
      the cine displacement-encoded MRI pulse sequence.

PMID- 17211868
TI  - Dual regulation of astrocyte gap junction hemichannels by growth factors and a
      pro-inflammatory cytokine via the mitogen-activated protein kinase cascade.
AB  - Evidence that glutamate and ATP release from astrocytes can occur via gap
      junction hemichannels (GJHCs) is accumulating. However, the GJHC is still only
      one possible release mechanism and has not been detected in some studies,
      although this may be because the levels were below those detectable by the system
      used. Because of these conflicting results, we hypothesized that release from
      astrocyte GJHCs might depend on different astrocyte states, and screened for
      factors affecting astrocyte GJHC activity by measuring fluorescent dye leakage
      via GJHCs using a conventional method for GJHC acivation, i.e. removal of
      extracellular divalent cations. Astrocytes cultured in Dulbecco's minimal
      essential medium containing 10% fetal calf serum, a medium widely used for
      astrocyte studies, did not show dye leakage, whereas those cultured in a defined
      medium showed substantial dye leakage, which was confirmed pharmacologically to
      be due to GJHCs and not to P2x7 receptors. EGF and bFGF inhibited the GJHC
      activity via the mitogen-activated protein kinase cascade, and the effect of the
      growth factors was reversed by interleukin-1beta. These factors altered GJHC
      activity within 10 min, but did not affect connexin 43 expression. GJHC activity
      in hippocampal slice culture preparations was measured using the same methods and
      found to be regulated in a similar manner. These results indicate that astrocyte
      GJHC activity is regulated by brain environmental factors.

PMID- 17211869
TI  - Kojic acid-tripeptide amide as a new tyrosinase inhibitor.
AB  - Twenty two kojic acid-tripeptide amides were prepared using a solid-phase
      Fmoc/tBu strategy with Rink Amide SURE(R) resin. To effectively obtain kojic acid
      tripeptide amide conjugates, the coupling conditions of kojic acid to the
      tripeptide on the resin were optimized. The tyrosinase inhibitory activity of
      kojic acid-tripeptide amides and the effect of the amino acid sequence on the
      activity were compared with those of kojic acid-tripeptide acids. The stability
      of kojic acid-tripeptide amides were then compared with those of kojic acid and
      kojic acid-tripeptides acids. As a consequence, kojic acid-FWY-NH(2) proved to be
      the best compound, with the highest inhibitory activity, which was maintained
      over different storage times under various temperatures and pHs.

PMID- 17211870
TI  - Administration time estimates for Wechsler Intelligence Scale for Children-IV
      subtests, composites, and short forms.
AB  - The administration times for Wechsler Intelligence Scale for Children-IV (WISC
      IV) subtests, indexes, and the Full Scale IQ were recorded for 57 school
      children. Also determined were administration times for eight short forms and the
      General Ability Index (GAI). All eight short forms reduced testing time by >50%,
      but the GAI required approximately 56 minutes. The time to administer the 10 core
      subtests that yield the Full Scale IQ and index scores averaged 72 minutes (range
      = 42 to 100), but 31% of the administrations required 80 minutes or longer. These
      results indicate that administration times are quite variable and that D.
      Wechsler's (2003) guideline of 65 to 80 minutes can be misleading for certain
      settings and for specific examinees. The present research found administration
      time to be positively correlated with examinee age, grade placement, and Full
      Scale IQ. In addition, the extent of examiner experience is known to be
      positively related to administration speed. In the present research, as in many
      settings, the examiners were competent, but not highly experienced.

PMID- 17211871
TI  - Young adults' ideas of cure prior to psychoanalytic psychotherapy.
AB  - The study aims to explore systematically the ideas of cure among young adults
      prior to psychoanalytic psychotherapy. Forty-six individuals aged 18 to 25 years
      who applied for psychotherapy underwent the Private Theories Interview (PTI).
      Twenty distinct categories of ideas of cure were identified. Based on these
      categories, a theoretical model was constructed with the dimensions, Approaching
      Distancing and Doing-Receiving. Individuals were classified into types using
      "ideal type analysis." Seven ideal types were formed: Processing and
      Understanding, Mastering Through Own Will and Action, Talking, Discordant Ideas,
      Incoherent Ideas, Getting It Out, and Avoiding or Placing the Solution onto
      Others. New hypotheses emerged concerning ideas of cure as an important factor
      for psychotherapy matching, thus potentially predicting premature termination,
      alliance, and outcome.

PMID- 17211872
TI  - An allelic series for studying the mouse Thoc1 gene.
AB  - Thoc1 encodes an essential component of the mammalian TREX protein complex. TREX
      is an evolutionary conserved complex that couples elongating RNA polymerase II
      with RNA processing factors. Depletion of Thoc1 protein (pThoc1) compromises
      transcriptional elongation and nuclear export of some RNAs. Loss of Thoc1 causes
      periimplantation embryonic lethality in the mouse. Early embryonic lethality
      precludes analysis of the physiological requirements for Thoc1 in the developing
      embryo or adult. To circumvent this limitation, we have generated mice containing
      hypomorphic or conditional alleles of Thoc1. Mice homozygous for the conditional
      allele appear normal. Mice containing Cre recombined conditional alleles
      phenocopy the previously characterized Thoc1 null allele. Mice homozygous for the
      hypomorphic allele are viable and born at a frequency that is not significantly
      different from the expected Mendelian ratio. However, these mice express less
      pThoc1 than wild type mice and exhibit a dwarf phenotype. The dwarf phenotype can
      be detected in mid-gestation embryos, suggesting that Thoc1 is also required
      later in embryonic and postnatal development.

PMID- 17211873
TI  - Utility of the Psychological Screening Inventory: a review.
AB  - The Psychological Screening Inventory (PSI; R. I. Lanyon, 1970, 1973, 1978, 1993,
      2006) was developed as a cost-effective screening device in identifying persons
      for whom a more complete psychological evaluation should be conducted. The author
      reviews data bearing on the utility of the PSI in this regard and in more general
      applications. The Alienation scale showed strong effect sizes in distinguishing
      psychiatric inpatients from controls, the Social Nonconformity scale in
      distinguishing incarcerated groups from control, and the Discomfort scale in
      identifying persons with general psychological distress. These findings were
      supported by correlational data with comparable scales, and by a variety of
      smaller comparison studies. Meaningful discriminations were also shown for
      adolescents and for college-age young adults. Findings in studies of substance
      abusers and medical problems were also reviewed. Response Distortion scales
      showed effectiveness similar to that of the Minnesota Multiphasic Personality
      Inventory-2 (MMPI-2; J. N. Butcher, W. G. Dahlstrom, J. R. Graham, A. Tellegen, &
      B. Kaemmer, 1989) validity scales. Validity was also shown for several of the
      seven available foreign language translations. It was concluded that the PSI is
      effective for the tasks for which it was designed.

PMID- 17211874
TI  - Seeking help from a mental health professional: the influence of one's social
      network.
AB  - The decision to seek psychological help may be hindered or facilitated by many
      factors. Two potential factors that might facilitate help seeking are having a
      relationship with someone (a) who recommends seeking help or (b) who themselves
      have sought help. In two studies (N = 780, N = 746), we explored the relationship
      between these factors and intentions to seek mental health services. In Study 1,
      being prompted to seek help and knowing someone who had sought help were both
      related to positive expectations about mental health services. In Study 2, being
      prompted to seek help and knowing someone who had sought help were related to
      more positive attitudes toward help seeking. Also, knowing someone who had sought
      help was related to the intention to seek help. Of those who sought psychological
      help, approximately 75% had someone recommend that they seek help and about 94%
      knew someone who had sought help.

PMID- 17211875
TI  - Interpersonal profiles in major depressive disorder.
AB  - Although patients with mood disorders report interpersonal difficulties in
      addition to depression or anxiety, few studies have examined interpersonal
      patterns in those patients. Here the authors' goals were to (a) identify the
      interpersonal pattern in patients with major depressive disorder (MDD), (b)
      determine interpersonal differences between subgroups of MDD patients, and (c)
      examine the interpersonal patterns of comorbid MDD patients. One- hundred forty
      one MDD adults participated in an ongoing randomized clinical trial of treatments
      for depression. Interpersonal profiles revealed that MDD patients were
      significantly more distressed by interpersonal problems than normative samples.
      Furthermore, MDD patients with depressive personality disorder reported more
      interpersonal distress than MDD-only patients report and were more likely to have
      interpersonal problems related to dominance and control than submissiveness.

PMID- 17211876
TI  - Does psychotherapy research inform treatment decisions in private practice?
AB  - Psychologists in independent practice (N = 591) were surveyed regarding their
      approach to treatment decisions, specifically the use of research on empirically
      supported treatments (ESTs) to inform practice. All participants received a case
      study of a patient with panic disorder, and half were randomly assigned to
      receive a research summary on evidence-based treatments for panic disorder
      (cognitive-behavioral therapy and pharmacotherapy). Practitioners reported that
      they rely primarily on clinical experiences to inform treatment decisions,
      although they often consult EST literature. Those who received the research
      summary were significantly more likely to report they would use an EST. These
      results indicate that providing information about ESTs can impact practice.
      Although this sample was more positive about EST research than clinicians are
      often depicted to be, this study indicates an enduring research-practice gap in
      clinical psychology.

PMID- 17211878
TI  - Rearrangement of a conditional allele regardless of inheritance of a Cre
      recombinase transgene.
AB  - To generate conditional gene knockouts in osteoblasts, we previously developed
      transgenic mice in which Cre recombinase cDNA was cloned downstream of a 3.6 or
      2.3 kb fragment of the rat Col1a1 promoter (Col3.6-Cre and Col2.3-Cre,
      respectively). Col-Cre mice were bred with mice in which exon 4 of the Igf1 gene
      is flanked by loxP sites. Mating units were arranged such that either the male or
      the female breeder transmitted the Col-Cre transgenes. Progeny were evaluated for
      Cre-mediated Igf1 gene rearrangement. We found that the loxP-flanked Igf1 locus
      was rearranged in the absence of inheritance of the Cre transgene. The incidence
      was 50 and 28% with Col2.3-Cre and Col3.6-Cre females, respectively, and 15 and
      18% with Col2.3-Cre and Col3.6-Cre males, respectively.

PMID- 17211877
TI  - Generation of a transgenic mouse model with chondrocyte-specific and tamoxifen
      inducible expression of Cre recombinase.
AB  - Postnatal cartilage development and growth are regulated by key growth factors
      and signaling molecules. To fully understand the function of these regulators, an
      inducible and chondrocyte-specific gene deletion system needs to be established
      to circumvent the perinatal lethality. In this report, we have generated a
      transgenic mouse model (Col2a1-CreER(T2)) in which expression of the Cre
      recombinase is driven by the chondrocyte-specific col2a1 promoter in a tamoxifen
      inducible manner. To determine the specificity and efficiency of the Cre
      recombination, we have bred Col2a1-CreER(T2) mice with Rosa26R reporter mice. The
      X-Gal staining showed that the Cre recombination is specifically achieved in
      cartilage tissues with tamoxifen-induction. In vitro experiments of chondrocyte
      cell culture also demonstrate the 4-hydroxy tamoxifen-induced Cre recombination.
      These results demonstrate that Col2a1-CreER(T2) transgenic mice can be used as a
      valuable tool for an inducible and chondrocyte-specific gene deletion approach.

PMID- 17211879
TI  - Flow cytometry to sort mammalian cells in cytokinesis.
AB  - BACKGROUND: Cell division or cytokinesis, which results from a series of events
      starting in metaphase, is the mechanism by which the mother cell cytoplasm is
      divided between the two daughter cells. Hence it is the final step of the cell
      division cycle. The aim of the present study was to demonstrate that mammalian
      cells undergoing cytokinesis can be sorted selectively by flow cytometry.
      MATERIALS AND METHODS: Cultures of HeLa cells were arrested in prometaphase by
      nocodazole, collected by mitotic shake-off and released for 90 min into fresh
      medium to enrich for cells undergoing cytokinesis. After ethanol fixation and DNA
      staining, cells were sorted based on DNA content and DNA fluorescence signal
      height. RESULTS: We define a cell population that transiently accumulates when
      synchronized cells exit mitosis before their entry into G1. We show that this
      population is highly enriched in cells undergoing cytokinesis. In addition, this
      population of cells can be sorted and analyzed by immunofluorescence and western
      blotting. CONCLUSIONS: This method of cell synchronization and sorting provides a
      simple means to isolate and biochemically analyze cells in cytokinesis, a period
      of the cell cycle that has been difficult to study by cell fractionation.

PMID- 17211880
TI  - Fully automated segmentation and morphometrical analysis of muscle fiber images.
AB  - BACKGROUND: Measurement of muscle fiber size and determination of size
      distribution is important in the assessment of neuromuscular disease. Fiber size
      estimation by simple inspection is inaccurate and subjective. Manual segmentation
      and measurement are time-consuming and tedious. We therefore propose an automated
      image analysis method for objective, reproducible, and time-saving measurement of
      muscle fibers in routinely hematoxylin-eosin stained cryostat sections. METHODS:
      The proposed segmentation technique makes use of recent advances in level set
      based segmentation, where classical edge based active contours are extended by
      region based cues, such as color and texture. Segmentation and measurement are
      performed fully automatically. Multiple morphometric parameters, i.e., cross
      sectional area, lesser diameter, and perimeter are assessed in a single pass. The
      performance of the computed method was compared to results obtained by manual
      measurement by experts. RESULTS: The correct classification rate of the computed
      method was high (98%). Segmentation and measurement results obtained manually or
      automatically did not reveal any significant differences. CONCLUSIONS: The
      presented region based active contour approach has been proven to accurately
      segment and measure muscle fibers. Complete automation minimizes user
      interaction, thus, batch processing, as well as objective and reproducible muscle
      fiber morphometry are provided.

PMID- 17211881
TI  - Combination of automated high throughput platforms, flow cytometry, and
      hierarchical clustering to detect cell state.
AB  - BACKGROUND: This study examined whether hierarchical clustering could be used to
      detect cell states induced by treatment combinations that were generated through
      automation and high-throughput (HT) technology. Data-mining techniques were used
      to analyze the large experimental data sets to determine whether nonlinear, non
      obvious responses could be extracted from the data. METHODS: Unary, binary, and
      ternary combinations of pharmacological factors (examples of stimuli) were used
      to induce differentiation of HL-60 cells using a HT automated approach. Cell
      profiles were analyzed by incorporating hierarchical clustering methods on data
      collected by flow cytometry. Data-mining techniques were used to explore the
      combinatorial space for nonlinear, unexpected events. Additional small-scale,
      follow-up experiments were performed on cellular profiles of interest. RESULTS:
      Multiple, distinct cellular profiles were detected using hierarchical clustering
      of expressed cell-surface antigens. Data-mining of this large, complex data set
      retrieved cases of both factor dominance and cooperativity, as well as atypical
      cellular profiles. Follow-up experiments found that treatment combinations
      producing "atypical cell types" made those cells more susceptible to apoptosis.
      CONCLUSIONS Hierarchical clustering and other data-mining techniques were applied
      to analyze large data sets from HT flow cytometry. From each sample, the data set
      was filtered and used to define discrete, usable states that were then related
      back to their original formulations. Analysis of resultant cell populations
      induced by a multitude of treatments identified unexpected phenotypes and
      nonlinear response profiles.

PMID- 17211882
TI  - Chromatin supraorganization and extensibility in mouse hepatocytes with
      development and aging.
AB  - BACKGROUND: Chromatin supraorganization and extensibility, which lead to the
      formation of extended chromatin fibers (ECF), are affected by starvation and
      refeeding in adult mouse hepatocytes. It is expected that they could also change
      with mouse development and aging. METHODS: Methods used involved topochemistry,
      image analysis, microspectrophotometry, gravity action, and polarization
      microscopy. RESULTS: Increased nuclear areas and Feulgen-DNA amounts with
      advancing hepatocyte polyploidy were found with development and aging. A slightly
      less packed chromatin with more heterogeneously distributed condensation levels
      was detected in young and old mice. Con-A responsiveness was almost absent in
      young mice but very deep in aged mice. ECFs formed from nuclei of adult and aged
      mice but not from nuclei of young mice. The frequency of ECF formation with the
      long lysis protocol increased with aging. CONCLUSIONS: In young mice, a less
      packed chromatin state may be associated with more intense gene activity, thus
      increasing the DNA-nuclear matrix interactions, and inhibiting ECF formation.
      Reduced DNA-nuclear matrix interactions besides defects in heterochromatin
      formation may induce higher ECF formation and chromatin unpackaging in old mice.
      We suggest that differences in Con-A staining relate to different gene activity
      with advancing development and aging.

PMID- 17211883
TI  - Breast conservation: current results and future perspectives at the European
      Institute of Oncology.
AB  - In the recent 10 years breast cancer treatments' scenario is radically changed.
      Extraordinary new surgical approaches give more and more conservative solutions
      both for the breast and especially for the axilla avoiding dissection in more
      than 80% of early cases. Instrumental early diagnosis and clinical prediction are
      now able to identify very initial cases often in premalignant stage. Technology
      arrived in the operating theatre for the intraoperative radiotherapy treatments
      giving to the patients the better quality of life with the help also of the
      plastic surgeons. There are still near horizons to reach: modern neo-adjuvant and
      adjuvant treatments are going quickly from the laboratory to patient's bed.

PMID- 17211884
TI  - C-myc activation impairs the NF-kappaB and the interferon response: implications
      for the pathogenesis of Burkitt's lymphoma.
AB  - Deregulation of the proto-oncogene c-myc is a key event in the pathogenesis of
      many tumors. A paradigm is the activation of the c-myc gene by chromosomal
      translocations in Burkitt lymphoma (BL). Despite expression of a restricted set
      of Epstein-Barr viral (EBV) antigens, BL cells are not recognized by antigen
      specific cytotoxic T cells (CTLs) because of their inability to process and
      present HLA class I-restricted antigens. In contrast, cells of EBV-driven
      posttransplant lymphoproliferative disease (PTLD) are recognized and rejected by
      EBV-specific CTLs. It is not known whether the poor immunogenicity of BL cells is
      due to nonexpression of viral antigens, overexpression of c-myc, or both. To
      understand the basis for immune recognition and escape, we have compared the mRNA
      expression profiles of BL and EBV-immortalized cells (as PTLD model). Among the
      genes expressed at low level in BL cells, we have identified many genes involved
      in the NF-kappaB and interferon response that play a pivotal role in antigen
      presentation and immune recognition. Using a cell line in which EBNA2 and c-myc
      can be regulated at will, we show that c-MYC negatively regulates STAT1, the
      central player linking the Type-I and Type-II interferon response. Switching off
      c-myc expression leads to STAT1 induction through a direct and indirect mechanism
      involving induction of Type-I interferons. c-MYC thus masks an interferon
      inducing activity in these cells. Our findings imply that immune escape of tumor
      cells is not only a matter of in vivo selection but may be additionally promoted
      by activation of a cellular oncogene.

PMID- 17211885
TI  - Chromatin dynamics of unfolding and refolding controlled by the nucleosome repeat
      length and the linker and core histones.
AB  - Chromatin is composed of genomic DNA and histones, forming a hierarchical
      architecture in the nucleus. The chromatin hierarchy is common among eukaryotes
      despite different intrinsic properties of the genome. To investigate an effect of
      the differences in genome organization, chromatin unfolding processes were
      comparatively analyzed using Schizosaccaromyces pombe, Saccharomyces cerevisiae,
      and chicken erythrocyte. NaCl titration showed dynamic changes of the chromatin.
      400-1000 mM NaCl facilitated beads with approximately 115 nm in diameter in S.
      pombe chromatin. A similar transition was also observed in S. cerevisiae
      chromatin. This process did not involve core histone dissociation from the
      chromatin, and the persistence length after the transition was approximately 26
      nm for S. pombe and approximately 28 nm for S. cerevisiae, indicating a salt
      induced unfolding to "beads-on-a-string" fibers. Reduced salt concentration
      recovered the original structure, suggesting that electrostatic interaction would
      regulate this discrete folding-unfolding process. On the other hand, the linker
      histone was extracted from chicken chromatin at 400 mM NaCl, and AFM observed the
      "beads-on-a-string" fibers around a nucleus. Unlike yeast chromatin, therefore,
      this unfolding was irreversible because of linker histone dissociation. These
      results indicate that the chromatin unfolding and refolding depend on the
      presence and absence of the linker histone, and the length of the linker DNA.

PMID- 17211886
TI  - Intramolecular and intermolecular guanine quadruplexes of DNA in aqueous salt and
      ethanol solutions.
AB  - DNA guanine quadruplexes are all based on stacks of guanine tetrads, but they can
      be of many types differing by mutual strand orientation, topology, position and
      structure of loops, and the number of DNA molecules constituting their structure.
      Here we have studied a series of nine DNA fragments (G(3)Xn)(3)G(3), where X = A,
      C or T, and n = 1, 2 or 3, to find how the particular bases and their numbers
      enable folding of the molecule into quadruplex and what type of quadruplex is
      formed. We show that any single base between G(3) blocks gives rise to only four
      molecular parallel-stranded quadruplexes in water solutions. In contrast to
      previous models, even two Ts in potential loops lead to tetramolecular parallel
      quadruplexes and only three consecutive Ts lead to an intramolecular quadruplex,
      which is antiparallel. Adenines make the DNA less prone to quadruplex formation.
      (G(3)A(2))(3)G(3) folds into an intramolecular antiparallel quadruplex. The same
      is true with (G(3)A(3))(3)G(3) but only in KCl. In NaCl or LiCl,
      (G(3)A(3))(3)G(3) prefers to generate homoduplexes. Cytosine still more
      interferes with the quadruplex, which only is generated by (G(3)C)(3)G(3),
      whereas (G(3)C(2))(3)G(3) and (G(3)C(3))(3)G(3) generate hairpins and/or
      homoduplexes. Ethanol is a more potent DNA guanine quadruplex inducer than are
      ions in water solutions. It promotes intramolecular folding and parallel
      orientation of quadruplex strands, which rather corresponds to quadruplex
      structures observed in crystals.

PMID- 17211887
TI  - DNA bending induced by carbocyclic sugar analogs constrained to the north
      conformation.
AB  - DNA bending caused by introduction of carbocyclic sugars constrained to the north
      conformation was studied, using explicit solvent molecular dynamic (MD)
      simulations. The native Drew-Dickerson (DD) dodecamer and its three modifications
      containing north carbocyclic sugars in the 7th (T7*), 8th (T8*) or both 7th and
      8th (T7T8*) nucleotide positions were examined. Introduction of the carbocyclic
      sugar results in A-form conformations for the alpha, beta, chi, zeta, and sugar
      pucker backbone parameters in the modified nucleotides. Increased steric
      repulsion between the sugar and its parent base in the modified oligonucleotides
      impacts the roll and cup dinucleotide step parameters, increasing the bending of
      the oligomer axis. Increased buckling of the substituted nucleotides disrupts the
      usual stabilizing base stacking interactions. The level of overall bending
      depends on the number and position of carbocyclic sugars introduced in the DNA
      sequence. Single sugar substitutions are unable to induce substantial bending due
      to the neighboring unmodified nucleotides counterbalancing the distortion.
      Significant bending can, however, be induced by two consecutive north sugars
      (T7T8*), which is in agreement with experimental results. The modified oligomers
      populate a wide range of bend angles, indicating that they maintain flexibility
      in the bent state. The present results suggest that insertion of carbocyclic
      sugars into DNA or RNA duplexes can be used to engineer bending of the duplexes
      without impacting the electrostatic or chemical properties of the phosphodiester
      backbone, thereby serving as excellent tools for experimental elucidation of
      nucleic acid structure-function relationships.

PMID- 17211888
TI  - Hydration study of homopolypeptides by (2)H NMR.
AB  - Deuteron T(1) and T(2) was studied as a function of hydration in homopolyglycine
      (PG) and homopolyproline (PP). Water deuteron relaxation rates in PG conform to a
      hydration model involving two types of primary hydration sites where water is
      directly bonded to the polymer. Once these sites are filled, additional water
      only bonds to water molecules at the primary sites and in so doing affect their
      dynamics. PP exhibits an anomalous T(1) and T(2) hydration dependence which has
      been interpreted in terms of a cooperative water molecule-PP molecule helical
      conformational rearrangement which occurs once a certain hydration level is
      reached. The proposal of a water-PP structure is tested using molecular dynamics
      simulations.

PMID- 17211889
TI  - Sequence-based modeling of Abeta42 soluble oligomers.
AB  - Abeta fibrils, which are central to the pathology of Alzheimer's disease, form a
      cross-beta-structure that contains likely parallel beta-sheets with a salt bridge
      between residues Asp23 and Lys28. Recent studies suggest that soluble oligomers
      of amyloid peptides have neurotoxic effects in cell cultures, raising the
      interest in studying the structures of these intermediate forms. Here, we present
      three models of possible soluble Abeta forms based on the sequences similarities,
      assumed to support local structural similarities, of the Abeta peptide with
      fragments of three proteins (adhesin, Semliki Forest virus capsid protein, and
      transthyretin). These three models share a similar structure in the C-terminal
      region composed of two beta-strands connected by a loop, which contain the Asp23
      Lys28 salt bridge. This segment is also structurally well conserved in Abeta
      fibril forms. Differences between the three monomeric models occur in the N
      terminal region and in the C-terminal tail. These three models might sample some
      of the most stable conformers of the soluble Abeta peptide within oligomeric
      assemblies, which were modeled here in the form of dimers, trimers, tetramers,
      and hexamers. The consistency of these models is discussed with respect to
      available experimental and theoretical data.

PMID- 17211890
TI  - The oxidizing enzyme CYP26a1 tightly regulates the availability of retinoic acid
      in the gastrulating mouse embryo to ensure proper head development and
      vasculogenesis.
AB  - Retinoic acid (RA) has been implicated as one of the signals providing a
      posterior character to the developing vertebrate central nervous system.
      Embryonic RA first appears in the posterior region of the gastrulating embryo up
      to the node level, where it may signal within the adjacent epiblast and/or newly
      induced neural plate to induce a hindbrain and spinal cord fate. Conversely,
      rostral head development requires forebrain-inducing signals produced by the
      anterior visceral endoderm and/or prechordal mesoderm, and there is evidence that
      RA receptors must be in an unliganded state to ensure proper head development. As
      RA is a diffusible lipophilic molecule, some mechanism(s) must therefore have
      evolved to prevent activation of RA targets in anterior regions of the embryo.
      This might result from RA catabolism mediated by the CYP26A1 oxidizing enzyme,
      which is transiently expressed in anteriormost embryonic tissues; however,
      previous analysis of Cyp26a1(-/-) mouse mutants did not clearly support this
      hypothesis. Here we show that Cyp26a1(-/-) null mutants undergo head truncations
      when exposed to maternally-derived RA, at doses that do not affect wild-type head
      development. These anomalies are linked to a widespread ectopic RA signaling
      activity in rostral head tissues of CYP26A1-deficient embryos. Thus, CYP26A1 is
      required in the anterior region of the gastrulating mouse embryo to prevent
      teratological effects that may result from RA signaling. We also report a novel
      role of CYP26A1 during early development of the intra- and extra-embryonic
      vascular networks.

PMID- 17211891
TI  - Protein-RNA contacts at crystal packing surfaces.
AB  - The crystal packing surfaces comprising protein-RNA interactions were analyzed
      for 50 RNA-protein crystal structures in the Protein Data Bank database. Protein
      RNA crystal contacts, which represent nonspecific protein-RNA interfaces, were
      investigated for their amino acid propensities, hydrogen bond patterns, and
      backbone and side chain interactions. When compared to biologically relevant
      interactions, the protein-RNA crystal contacts exhibit similarities as well as
      differences with respect to the principles of protein-RNA interactions. Similar
      to what was observed at cognate protein-RNA interfaces, positively charged amino
      acids have high propensities at noncognate protein-RNA interfaces and
      preferentially form hydrogen bonds with RNA phosphate groups. In contrast,
      nonpolar residues are less frequently associated with noncognate interactions.
      These results highlight the important roles of both electrostatic and hydrogen
      bonding interactions, facilitated by positively charged amino acids, in mediating
      both specific and nonspecific protein-RNA interactions.

PMID- 17211892
TI  - Modelling of the ABL and ARG proteins predicts two functionally critical regions
      that are natively unfolded.
AB  - The ABL and ARG tyrosine kinases regulate many pivotal cellular processes and are
      implicated in the pathogenesis of several forms of leukemia. We have modelled the
      previously uncharacterized core domain (SH3-SH2-tyrosine kinase) and C-terminal
      actin-binding domain of ARG. We have also investigated the structural arrangement
      of the ABL and ARG Cap region and of the long multifunctional region located
      downstream of the tyrosine kinase domain. We report that the ARG core domain is
      homologous to the corresponding ABL region, therefore suggesting that ARG
      catalytic activity is likely regulated by the same SH3-SH2 clamp described for
      ABL. We also report that the Cap of both ABL and ARG is natively unfolded. Hence,
      biological events determining the folding of the Cap are critical to allow its
      interaction with the tyrosine kinase C-lobe. Furthermore, our results show that,
      with the exception of the C-terminal actin-binding domain, the entire region
      encoded by the ABL and ARG last exon is natively unfolded. Phosphorylation events
      or protein-protein interactions regulating the folding of this region will
      therefore modulate the activity of its numerous functional domains. Finally, our
      analyses show that the C-terminal actin-binding domain of ARG displays a four
      helix bundle structure similar to the one reported for the corresponding ABL
      region. Our findings imply that many biological activities attributed to ABL,
      ARG, and their oncogenic counterparts are regulated by natively unfolded regions.

PMID- 17211893
TI  - Characterization of a corrinoid protein involved in the C1 metabolism of strict
      anaerobic bacterium Moorella thermoacetica.
AB  - The strict anaerobic, thermophilic bacterium Moorella thermoacetica metabolizes
      C1 compounds for example CO(2)/H(2), CO, formate, and methanol into acetate via
      the Wood/Ljungdahl pathway. Some of the key steps in this pathway include the
      metabolism of the C1 compounds into the methyl group of methylenetetrahydrofolate
      (MTHF) and the transfer of the methyl group from MTHF to the methyl group of
      acetyl-CoA catalyzed by methyltransferase, corrinoid protein and CO
      dehydrogenase/acetyl CoA synthase. Recently, we reported the crystallization of a
      25 kDa methanol-induced corrinoid protein from M. thermoacetica (Zhou et al.,
      Acta Crystallogr F 2005; 61:537-540). In this study we analyzed the crystal
      structure of the 25 kDa protein and provide genetic and biochemical evidences
      supporting its role in the methanol metabolism of M. thermoacetia. The 25 kDa
      protein was encoded by orf1948 of contig 303 in the M. thermoacetica genome. It
      resembles similarity to MtaC the corrinoid protein of the methanol:CoM
      methyltransferase system of methane producing archaea. The latter enzyme system
      also contains two additional enzymes MtaA and MtaB. Homologs of MtaA and MtaB
      were found to be encoded by orf2632 of contig 303 and orf1949 of contig 309,
      respectively, in the M. thermoacetica genome. The orf1948 and orf1949 were co
      transcribed from a single polycistronic operon. Metal analysis and spectroscopic
      data confirmed the presence of cobalt and the corrinoid in the purified 25 kDa
      protein. High resolution X-ray crystal structure of the purified 25 kDa protein
      revealed corrinoid as methylcobalamin with the imidazole of histidine as the
      alpha-axial ligand replacing benziimidazole, suggesting base-off configuration
      for the corrinoid. Methanol significantly activated the expression of the 25 kDa
      protein. Cyanide and nitrate inhibited methanol metabolism and suppressed the
      level of the 25 kDa protein. The results suggest a role of the 25 kDa protein in
      the methanol metabolism of M. thermoacetica.

PMID- 17211894
TI  - Impact of three-dimensional characteristics of the left main coronary artery
      bifurcation on outcome of crush stenting.
AB  - BACKGROUND: Crush stenting with drug-eluting stents is used to treat left main
      coronary artery (LMCA) bifurcations. However, the rate of restenosis at the left
      circumflex (LCX) artery ostium is high. The impact of the three-dimensional (3D)
      structure of LMCA bifurcation on the outcome of crush stenting with respect to
      restenosis has not been described. OBJECTIVES: This study examined the stent
      expansion, deformity, overlapping, and apposition after crush stenting of LMCA
      bifurcations. METHODS: Bare metal stents were crushed at LMCA bifurcations in a
      3D model that reproduced actual angles, such that the stent deployed from the
      LMCA to the left anterior descending (LAD) artery crushed the stent deployed from
      the LMCA to the LCX, followed by kissing balloon inflation. The stents were
      inspected under fluoroscopy and endoscopy. The effect of the bifurcation angle on
      stent expansion was also examined. RESULTS: In the 3D model, one stent overlapped
      the other in the distal LMCA, in contrast to the nearly parallel position of the
      stents observed in a separate two-dimensional model. When the LAD stent
      overlapped the LCX stent, the latter was crushed on the myocardial side of the
      vessel, and an unstented segment was observed on the nonmyocardial side, at the
      LCX ostium. When the overlap was reversed, the LCX stent was crushed on the
      nonmyocardial side and an unstented segment was observed on the myocardial side.
      A narrow LMCA-LCX angle was associated with less expansion of the LCX stent at
      the ostium than more distally, and with a higher likelihood of incomplete stent
      apposition. CONCLUSIONS: Overlap of the LAD stent over, as opposed to under, the
      LCX stent was associated with close apposition of the stent to the vessel on the
      myocardial side, at the ostium of the LCX artery, where atherosclerotic plaques
      are likely to be present. The spatial plaque burden and bifurcation angle should
      be closely examined before crush stenting, and segments should not be left
      unstented over large plaques.

PMID- 17211895
TI  - The interobserver reliability of off-line antral follicle counts made from stored
      three-dimensional ultrasound data: a comparative study of different measurement
      techniques.
AB  - OBJECTIVE: To assess the interobserver reliability of antral follicle counts
      (AFCs) made from stored three-dimensional (3D) ultrasound data using conventional
      two-dimensional (2D) images, 3D multiplanar view and 3D-rendered 'inversion
      mode'. METHODS: 3D transvaginal ultrasound was performed in the early follicular
      phase (days 2-5) of the menstrual cycle in 41 subjects aged < 40 years,
      undergoing investigation for subfertility. From the stored 3D ultrasound
      datasets, the number of antral follicles of 2-10 mm in diameter in each ovary was
      independently measured, using all three methods by three investigators, each with
      a different level of experience. The image quality of each dataset was
      subjectively categorized into one of three groups, based on the proportion of the
      ovarian contour that could be seen clearly. RESULTS: There was no significant
      difference in the mean AFC between the observers for any of the three different
      techniques. The intraclass correlation coefficient (ICC) for the 2D-equivalent
      mode, the 3D multiplanar mode, and the 3D-rendered inversion mode were indicative
      of good interobserver reliability for each method. The interobserver reliability
      for the 3D-rendered inversion mode was better with Grade 1 image quality than
      with Grade 3 image quality. There were no equivalent differences, however,
      between the three different grades of image quality with the 2D-equivalent and 3D
      multiplanar modes. The time taken for AFC measurement using 3D-rendered inversion
      mode was significantly longer than with the 2D equivalent and 3D multiplanar
      methods. CONCLUSIONS: 3D image displays and rendering techniques do not appear to
      offer any advantage over a conventional 2D display in terms of AFC measurement
      reliability. AFC measurement using the 3D-rendered inversion mode has an adequate
      interobserver reproducibility but is dependent on image quality.

PMID- 17211896
TI  - Peripheral white blood cell toxicity induced by broad spectrum cyclin-dependent
      kinase inhibitors.
AB  - Cyclin-dependent kinases (CDKs) have been pursued for more than a decade for the
      treatment of cancer. CDK inhibitors are expected to slow the rate of cell
      division and potentially increase the apoptotic fraction of rapidly dividing
      cells. Although CDK activity is often increased in tumors, normal dividing
      tissues are also susceptible to the cytostatic and cytotoxic effects of CDK
      inhibitor action. Therefore the typical toxicity profile associated with
      cytotoxic anti-cancer therapy, bone marrow suppression and gastrointestinal
      toxicity, is expected with CDK inhibitors. Bone marrow toxicity and the ensuing
      delayed peripheral leukocyte suppression often limit the therapeutic application
      of cytotoxic anticancer drugs. Here we characterize an unusual bone marrow
      independent acute toxicity toward leukocytes from broad spectrum CDK inhibitors
      in monkeys and rodents. The potential combination of both acute and delayed
      immunosuppression would likely further restrict the application of these
      particular compounds. Since the cells targeted were non-proliferating, it was
      assumed that the toxicity was not driven by the intended pharmacological
      mechanism thereby facilitating the development of a testing strategy to identify
      compounds with a reduced potential for acute leukocyte toxicity. This testing
      strategy resulted in a CDK inhibitor void of bone marrow-independent leukocyte
      toxicity that is currently undergoing clinical testing.

PMID- 17211897
TI  - By how much does increased nuchal translucency increase the risk of adverse
      pregnancy outcome in chromosomally normal fetuses? A study of 16,260 fetuses
      derived from an unselected pregnant population.
AB  - OBJECTIVE: In this study we aimed to estimate the magnitude of a possible
      increase in risk of adverse outcome in fetuses with normal karyotype and
      increased nuchal translucency (NT), and to determine how well NT measurements can
      distinguish between fetuses with normal and adverse outcome. METHODS: We studied
      16,260 consecutive fetuses with normal karyotype derived from an unselected
      pregnant population. The following cut-offs for increased risk of adverse outcome
      were chosen a priori: NT > or = 95th percentile, > or = 3 mm, > or = 3.5 mm, and
      > or = 4.5 mm. The positive and negative likelihood ratios (+LR, - LR) of the
      risk cut-offs with regard to fetal malformation, miscarriage, perinatal death,
      termination of pregnancy and total adverse outcome were calculated, and receiver
      operating characteristics (ROC) curves were drawn. RESULTS: The total rate of
      adverse outcome was 2.7%. + LR and - LR of NT > or = 3.0 mm were: for lethal or
      severe malformation, + LR 15.0 (95% CI 7.0-28.6), - LR 0.89 (95% CI 0.81-0.95);
      for malformation of at least intermediate severity, + LR 8.1 (95% CI 4.3-14.0), -
      LR 0.95 (95% CI 0.92-0.97); for termination of pregnancy, + LR 41.6 (95% CI 17.1
      86.6), - LR 0.67 (95% CI 0.41-0.85); for any adverse outcome, + LR 6.4 (95% CI
      3.4-11), - LR 0.96 (95% CI 0.94-0.98). The odds for these adverse outcomes
      increased with increasing NT. NT > or = 3 mm did not significantly increase the
      risk of miscarriage or perinatal death. Areas under ROC curves for NT were small,
      with 95% CI below or only slightly above 0.5. CONCLUSION: Our likelihood ratios
      can be used to calculate the individual risk of unfavorable outcome, but NT
      screening cannot reliably distinguish between normal and adverse outcome in
      fetuses with normal karyotype.

PMID- 17211898
TI  - Macrocyclic ferrocenyl-bisimidazoline palladacycle dimers as highly active and
      enantioselective catalysts for the aza-claisen rearrangement of Z-configured N
      para-methoxyphenyl trifluoroacetimidates.

PMID- 17211900
TI  - Structural rearrangements induced by photoexcitation in a RbCoFe Prussian blue
      derivative.

PMID- 17211899
TI  - Patterned paper as a platform for inexpensive, low-volume, portable bioassays.

PMID- 17211901
TI  - Backbone carbonyl group basicities are related to gas-phase fragmentation of
      peptides and protein folding.

PMID- 17211902
TI  - Aggregation behavior of tetraenoic fatty acids in aqueous solution.

PMID- 17211903
TI  - 1,3-dipolar cycloadditions of azides and alkynes: a universal ligation tool in
      polymer and materials science.
AB  - In 2001, Sharpless and co-workers introduced "click" chemistry, a new approach in
      organic synthesis that involves a handful of almost perfect chemical reactions.
      Among these carefully selected reactions, Huisgen 1,3-dipolar cycloadditions were
      shown to be the most effective and versatile and thus became the prime example of
      click chemistry. Hence, these long-neglected reactions were suddenly re
      established in organic synthesis and, in particular, have gained popularity in
      materials science. The number of publications dealing with click chemistry has
      grown exponentially over the last two years. The Minireview discusses whether
      click chemistry is a miracle tool or an ephemeral trend.

PMID- 17211904
TI  - Structure and total synthesis of lysobactin (katanosin B).

PMID- 17211905
TI  - Highly efficient, near-infrared electrophosphorescence from a Pt-metalloporphyrin
      complex.

PMID- 17211906
TI  - Catalytic asymmetric synthesis of tertiary alkyl chlorides.

PMID- 17211907
TI  - Effective chirality transfer in ionic liquids through ion-pairing effects.

PMID- 17211908
TI  - Enantioselective intramolecular aldol addition/dehydration reaction of a
      macrocyclic diketone: synthesis of the musk odorants (R)-muscone and (R,Z)-5
      muscenone.

PMID- 17211909
TI  - A terminal nitride-to-phosphide conversion sequence followed by tungsten
      phosphide functionalization using a diphenylphosphenium synthon.

PMID- 17211910
TI  - Ubiquitin binds to a short peptide segment of hydrolase UCH-L3: a study by FCS,
      RIfS, ITC and NMR.
AB  - Screening for small peptidic affinity tags for the detection of ubiquitin and
      ubiquitinated proteins yielded the dodecapeptide amide DPDELRFNAIAL-NH(2) as a
      specific ubiquitin-interacting ligand. A peptide collection--based on crystal
      structures with ubiquitin-interacting proteins--was designed and confirmed by
      sequence comparison of ubiquitin-interacting motifs. Four independent physical
      detection methods demonstrated that the peptide binds to monomeric ubiquitin with
      an affinity of about 10 muM and with fast on and off rates. Fluorescence
      correlation spectroscopy with fluorescent peptides showed specific interaction
      with ubiquitin. Reflectometric interference spectroscopy with surface-immobilized
      peptides and isothermal calorimetry measurements confirmed the specific binding
      of ubiquitin and fast rate constants. (1)H,(15)N heteronuclear NMR localised the
      interaction site across the beta sheet of ubiquitin. The peptide aligns well with
      the ubiquitin-interacting motif and represents a lead structure for the rational
      design of high-affinity tags for targeting ubiquitinated protein in vitro and in
      vivo.

PMID- 17211911
TI  - Dichloromethane as a selective modifying agent to create a family of highly
      reactive chromium polymerization sites.

PMID- 17211912
TI  - Engineering the structural properties of DNA block copolymer micelles by
      molecular recognition.

PMID- 17211913
TI  - A network of coiled-coil associations derived from synthetic GCN4 leucine-zipper
      arrays.

PMID- 17211914
TI  - Synthetic mimetics of the CD4 binding site of HIV-1 gp120 for the design of
      immunogens.

PMID- 17211915
TI  - Violating the isolated pentagon rule (IPR): the endohedral non-IPR C70 cage of
      Sc3N@C70.

PMID- 17211916
TI  - Indium-mediated asymmetric allylation of acylhydrazones using a chiral urea
      catalyst.

PMID- 17211917
TI  - Drug interactions. Putting out the fire of stomach acid.

PMID- 17211918
TI  - Drug interactions. Gilead's integrase inhibitor.

PMID- 17211919
TI  - Drug interactions. Kaletra and atazanavir.

PMID- 17211920
TI  - Drug interactions. Interactions with TMC114 and TMC125.

PMID- 17211921
TI  - Drug interactions. Amprenavir with low-dose ritonavir.

PMID- 17211922
TI  - The cost of chemoprevention.

PMID- 17211923
TI  - Battles still over framework 7.

PMID- 17211924
TI  - Speeding up cancer-drug development.

PMID- 17211925
TI  - The bottom line.

PMID- 17211926
TI  - Letter to the editor on "Nurse safety: have we addressed the risks?".

PMID- 17211927
TI  - Letter to the editor on "Reflections on the DNP and an alternate practice
      doctorate model: the Drexel model".

PMID- 17211928
TI  - Letter to the editor on "Vigilance: the essence of nursing".

PMID- 17211929
TI  - Letter to the editor on "The need for some sense making: doctor of nursing
      practice".

PMID- 17211930
TI  - Nicaragua tightens up abortion laws.

PMID- 17211932
TI  - The essence of the art of medicine.

PMID- 17211931
TI  - Kenya's mixed HIV/AIDS response.

PMID- 17211933
TI  - Diversity of primary health care providers for urban indigenous Australians.

PMID- 17211934
TI  - [Research in Luxembourg from the legislative point of view].
AB  - Since the independence of the grand-duchy of Luxembourg in 1839 it has taken a
      long time with complicated procedures to develop research in our country. The
      creation of a society for research and conservation of historical monuments goes
      back to 1845 followed by the Society of Natural Sciences in 1850, then by the
      Medical Society in 1862. Those 3 societies were at the origin of the Institut
      Grand Ducal. The creation of a Luxembourg institute for scientific research
      (CLRS) on April 1977 allowed a first public financing for research. The law of
      March 9th 1987 defined the type of research in 3 different centers of Public
      Research (CRP). On May 31st 1999 the National Fund of Research (FNR) was born.
      The author presents the different positions of the Council of State concerning
      these projects. The creation of the University of Luxembourg by law on July 17th
      2003 raised many problems of coordination, collaboration and competences. Some
      solutions of this imbroglio are suggested.

PMID- 17211935
TI  - [Sexually transmitted infections caused by Chlamydia].

PMID- 17211937
TI  - "The adipocyte: a multifunctional cell".
AB  - The beautiful Thorskog Castle just north of Goteborg on the Swedish west coast
      was the venue for the 134th Nobel Symposium, entitled "The Adipocyte: A
      Multifunctional Cell." For three splendid summer days, some 50 scientists working
      on various aspects of adipocyte biology convened under the auspices of the Nobel
      Foundation.

PMID- 17211936
TI  - [Whither spirometry?].

PMID- 17211938
TI  - Bibliography. Current world literature. New developments in urologic imaging.

PMID- 17211939
TI  - HIV/AIDS efforts are stagnating: accountability is key.

PMID- 17211940
TI  - Boost for South African AIDS programme while health minister is off sick.

PMID- 17211941
TI  - [Genetic research and preventive medicine].

PMID- 17211942
TI  - [A contribution to the study of mortality rates in Ghent during the 18th century:
      the case of Sint-Salvator].

PMID- 17211943
TI  - The narrative heart of the Renaissance.

PMID- 17211944
TI  - A pretty trifle: art and identity in Boswell's London journal.

PMID- 17211945
TI  - [Ivan Sergeyevich Kudrin (on his 100th birthday)].

PMID- 17211946
TI  - [From the 1898 repressions to Giolitti's "new course": institutional crisis and
      the beginning of "conservative reformism"].

PMID- 17211947
TI  - Comments on efforts to eradicate brucellosis.

PMID- 17211948
TI  - Qualities of successful food animal veterinarians.

PMID- 17211949
TI  - Propofol for endoscopy in Canada: a sleepy or a slippery slope? Dr Rakesh
      Bhandari is interviewed by Paul C Adams.

PMID- 17211950
TI  - Detection and genotypic characterization of Giardia cysts in water samples.
AB  - Water samples were collected from a wastewater treatment plant and from two lakes
      in the vicinity of Rome (Italy) for detection and genotypic characterization of
      Giardia. All wastewater samples and all but two of the lake samples were scored
      by immunofluorescence as positive for Giardia. In addition, Giardia cysts were
      detected, by nested PCR, in all of the examined samples. Analysis of the SSU-rRNA
      gene sequences showed that all Giardia isolates belonged to Assemblage A. The
      presence of Assemblage A genotype in wastewater and surface bathing water
      represents an important public health concern. In fact, isolates showing this
      genotype are considered to be potential human pathogens and also have zoonotic
      implications.

PMID- 17211951
TI  - Correction.

PMID- 17211952
TI  - Proceedings of the XIIIth World Congress on Gestational Trophoblastic Disease.
      October 23-26, 2005. Hong Kong.

PMID- 17211953
TI  - Vertical transmission of HCV infection: prospective study in infants born to HIV
      1 seronegative women.
AB  - OBJECTIVE: We performed a long-term prospective trial in infants born to HCV
      positive but HIV-1 negative women, with the aim of evaluating vertical
      transmission of HCV and correlated risks factors. METHODS: From April 1996 to May
      2002, 50 women in the 3rd trimester of pregnancy or close to delivery we enrolled
      in the study. Anti-HCV antibodies were detected by 2nd and 3rd generation ELISA
      tests (ABBOTT HCV 2nd EIA generation and MEIA Abbot Labs, IL) . Reactivity was
      confirmed by a commercial immunoblot (Abbott Matrix HCV 2.0) ad HCV-RNA was
      detected by a nested-PCR technique. Infants were prospectively followed by
      clinical and laboratory tests (ALT levels, anti HCV Ab and HCV RNA) every 3 or 6
      months for 16 to-80 months (average: 28.5 months). RESULTS: Twenty-eight of 50
      women (56%) were found positive for HCV-RNA at delivery, and in 17/50 no risk
      factors for HCV infection were identified. Vertical transmission of HCV was
      detected in 3/28 infants born to viremic mothers (10.7%), while none of the 22
      non-viremic mothers transmitted the infection to their children. Prolonged HCV
      seronegativity was documented in one of the three infected infants. During follow
      up three other infants presented a single positive PCR value; one infant resulted
      HCV positive at 51 months of age. All infants were anti-HCV positive at delivery
      due to passive acquisition of antibodies, and in the 44 uninfected infants the
      antibody titres decreased progressively and became negative at various intervals
      (3-18 months). CONCLUSION: The overall vertical transmission rate was 6% but the
      risk of transmission of HCV infection is limited to women that are HCV RNA
      positive at delivery. This study shows that vertical transmission of HCV
      infection possibly occurs in immunocompetent infants with no HCV antibodies
      detected in the serum. Furthermore, we emphasise that a prolonged follow-up is
      absolutely mandatory in order ot establish the occurrence of active infection.

PMID- 17211954
TI  - Proceedings of the 28th International Congress on Occupational Health. June 11
      16, 2006. Milan, Italy.

PMID- 17211955
TI  - [Abstracts of the Conference dedicated to the 70th Anniversary of the Tver' State
      Medical Academy and the centenary of birth of a founder of the Department of
      Human Anatomy Professor I S Kudrin].

PMID- 17211956
TI  - [Assessment of supply and demand for hip arthroplasty in Puglia (Italy) in the
      years 1996-2003].
AB  - Hip arthroplasty is one of the major achievements of orthopaedic surgery. In the
      Puglia region the demand for this procedure is moderately met. This study
      evaluates the regional distribution of hip arthroplasty procedures in Puglia in
      the years 1996-2003. Demand and supply was estimated through analysis of
      discharge abstract forms. Between 1996 and 203, 21,392 hip arthroplasty
      procedures were performed. of these, 12,491 (58,4%) were total hip
      arthroplasties, 7,742 (36,2%) were hip endoprostheses and 1,159 (5,4%) wee
      revisions. The median age of patients undergoing any of these procedures was 70
      years and the proportion of females was almost double that of males (64%). The
      main indication was primary osteoarthrosis and 52,1% of all procedures were
      performed in the province of Bari. The average annual crude hospitalisation rate
      for hip arthroplasty procedures was 75,9 cases/100.000 inhabitants; this rate
      places the Puglia region in an intermediate position with respect to other
      Italian regions and is lower than that found in the literature. Discharge
      abstract forms are currently the sole source of data regarding hip arthroplasty
      procedures and this presents several limits. This factor, in addition to the
      complexity and high costs of these procedures and to the increasing average life
      expectancy of the general population all point to the need for a regional Hip
      arthroplasty Register, which would allow better planning for patients.

PMID- 17211957
TI  - [A survey of the social and health conditions of immigrants living in the city of
      Messina (Italy)].
AB  - From december 2002 to May 2003 a questionnaire was administered to a sample of
      the immigrant population living in Messina (Italy), in order to evaluate their
      social and health conditions. Of great interest are data revealing that nearly
      all immigrants, despite being regularly enrolled in the Italian National Health
      Service (INHS), do not utilize available services when ill. The survey identified
      one of the reasons for this to be insufficient visibility and accessibility of
      the INHS in that time period.

PMID- 17211958
TI  - [Review and evaluation of waiting time indicators used in Italy].
AB  - In this study, a set of 15 indicators that are used to provide information on
      waiting times for medical services and procedures were evaluated. Each waiting
      time indicator was evaluated with respect to 14 criteria and given a score. The
      indicator "waiting time estimated through past performance" reached the highest
      score with respect to all others. This indicator is calculated by dividing the
      total number of individuals waiting for a medical procedure by the number of
      procedures performed in the facility in the previous month. The result is
      multiplied by thirty and expressed in days. This indicator can be used even in
      non-computerized facilities. It allows easy data accounting (at all levels, i.e
      service, facility, healthcare unit, area, regional and national level) and
      provides useful information for citizens/users.

PMID- 17211959
TI  - [Ottavio Lovera di Maria and the organization of Italian public security].

PMID- 17211960
TI  - [The "utopian" Madrid (1597-1600) of Cristobal Perez de Herrera].

PMID- 17211961
TI  - [Quality improvement, training and clinical governance: the role of the chief
      medical officer and his staff].
AB  - PURPOSE: To allow chief medical officers and their staff to contribute to
      implemented quality and clinical governance programs and consequently give a more
      precise identity, in terms of prestige and professional value, to a Structure
      that can contribute significantly to the development of a high quality hospital.
      METHODS: Terminology used was briefly described; tasks assigned to the chief
      medical officer and staff were then analysed and lastly, a hypothetical
      integrated training program was outlined for directors/managers. CONCLUSIONS:
      Quality and professional training represent important tools for human resources
      management policy. In this context, chief medical officers could contribute
      specific and significant technical expertise if the development and
      implementation of training wand quality improvement is given high priority in its
      own culture and is well integrated within the organization.

PMID- 17211962
TI  - The old man of Olduvai Gorge.

PMID- 17211963
TI  - Planning birth: changes in fertility culture in a Chinese village.

PMID- 17211964
TI  - GnRH agonist versus GnRH antagonist in ovarian stimulation: is the emperor naked?
AB  - OBJECTIVE: The aim of the study was to evaluate the influence of type of GnRH
      analog used during controlled ovarian hyperstimulation (COH) on the outcome of in
      vitro fertilization (IVF) cycles. PATIENTS AND METHODS: All consecutive women
      aged < or = 35 years admitted to our IVF unit from January 2001 to December 2004
      were enrolled in the study. Only patients undergoing up to their third IVF cycle
      attempt were included. Ovarian stimulation characteristics, number of oocytes
      retrieved, number of embryos transferred, and clinical pregnancy rate were
      compared between women given GnRH-agonist or GnRH-antagonist during COH. RESULTS:
      Four hundred and eighty-seven consecutive IVF cycles were evaluated, 226 in the
      agonist group and 261 in the antagonist group. A clinical pregnancy was achieved
      in 93 patients in the agonist group (pregnancy rate 41.2% per cycle) and 66
      patients in the antagonist grup (pregnancy rate 25.3%); this difference was
      statistically significant (p < 0.01). The agonist group also used significantly
      more gonadotropin ampoules, required longer stimulation, and had higher estradiol
      levels on the day of human chorionic gonadotropin administration. CONCLUSION: The
      midluteal long GhRH-agonist suppressive protocol should be the protocol of choice
      in young patients in their first three IVF cycle attempts.

PMID- 17211965
TI  - Double-blind, placebo-controlled study of Fertilityblend: a nutritional
      supplement for improving fertility in women.
AB  - PURPOSE: To determine the impact of nutritional supplementation on female
      fertility. METHODS: A double blind, placebo-controlled study of the effects of
      FertilityBlend for Women, a proprietary nutritional supplement containing
      chasteberry, green tea, L-arginine, vitamins (including folate) and minerals, on
      progesterone level, basal body temperature, menstrual cycle length, pregnancy
      rate and side-effects. RESULTS: Ninety-three (93) women, aged 24-42 years, who
      had tried unsuccessfully to conceive for six to 36 months, completed the study.
      After three months, the FertilityBlend (FB) group (N = 53) demonstrated a trend
      toward increased mean mid-luteal progesterone (P(ml)), but among women with basal
      pretreatment P(ml) < 9 ng/ml, the increase in progesterone was highly
      significant. The average number of days with luteal-phase basal temperatures over
      98 degrees F increased significantly in the FB group. Both short and long cycles
      (< 27 days or > 32 days pretreatment) were normalized in the FB group. The
      placebo group (N = 40) did not show any significant changes in these parameters.
      After three months, 14 of the 53 women in the FB group were pregnant (26%)
      compared to four of the 40 women in the placebo group (10%; p = 0.01). Three
      additional women conceived after six months on FB (32%). No significant side
      effects were noted. CONCLUSION: Nutritional supplements could provide an
      alternative or adjunct to conventional fertility therapies.

PMID- 17211966
TI  - A morphological and biochemical appraisal of the liver and renal effects of
      lamivudine on rat pregnancy.
AB  - No data exist on the perinatal safety of lamivudine alone, as it is used in
      combination with other antiretroviral agents. Until now, only preliminary data on
      the lamivudine-zidovudine combination have been available, thus we decided to
      examine the gross maternal and fetal effects of lamivudine administered alone
      during the entire period of rat pregnancy. Forty pregnant animals were assigned
      at random to four groups (C1 = control; E1 = 5 mg/kg; E2 = 15 mg/kg; E3 = 45
      mg/kg) from day 0 up to the 20th day of gestation. These doses were divided into
      two daily administrations by gavage. Controls (n = 10) received distilled water
      in the same schedule. At term-pregnancy, the rats were deeply anesthetized and
      blood samples were collected for alanine and aspartate aminotransferases,
      creatinine and urea determinations. Fragments of maternal and fetal livers and
      kidneys were taken and processed for histopathological study. In all groups blood
      transaminases were within the normal limits, as were the levels of creatinine and
      urea, thus indicating that treatment with lamivudine during the entire gestation
      was essentially devoid of liver or kidney effects which could result in altered
      metabolic parameters. Morphological (light microscopy) studies revealed that no
      significant effects of the drug could be detected regarding either maternal or
      fetal organs of the E1 and E2 groups. However, the maternal hepatocytes in the E3
      group showed heterochromatic nuclei. In addition, there was some fatty
      infiltration, congested sinusoids and portal dilatation. Maternal kidneys in the
      E3 group revealed vascular dilation around the convoluted tubules. It is
      concluded that only doses of lamivudine used during the entire gestation in doses
      well above the usual human doses could be considered to be potentially
      hepatotoxic for the pregnant rat.

PMID- 17211967
TI  - New emerging blood-borne hepatitis viral pathogens and the feasibility of passing
      thorough the placenta: an appraisal.
AB  - In countries with a high prevalence of blood-borne pathogen infections,
      transmission to infants commonly occurs from an infected mother during pregnancy.
      Maternal diseases caused by bacteria, viruses and parasites may sometimes be
      transmitted vertically. For many pathogens, several questions remain unanswered
      about the pathogenesis of vertical transmission, the relative risk associated
      with each mode of transmission, the rate of transmission from mother to child,
      and the factors that might contribute to the efficiency of transmission. There is
      also a need to quantify the contribution made by intrauterine versus intrapartum
      events. Here, the feasibility of some new emerging blood-borne hepatitis viral
      pathogens (hepatitis G virus, hepatitis SEN virus and hepatitis TT virus) passing
      through the placenta was analyzed based on a consideration of nonostructure
      level. Based on the particle size as a single factor, it is hereby proposed that
      the transmission of the studied viruses via the placenta is difficult. Possible
      infection due to other processes, especially intrapartum infection due to micro
      trauma delivery, similar to HIV infection, might be a more important route of
      vertical transmission.

PMID- 17211968
TI  - Effects of pregnancy and childbirth on the incidence of urinary disorders in
      multiple sclerosis.
AB  - OBJECTIVE: Women with multiple sclerosis frequently pose questions to physicians
      regarding the potential negative impact of pregnancy, especially on urinary
      disorders. About 50 to 80% of patients suffer from urinary disorders during the
      course of the disease. Trauma to the pelvic floor and the urethral sphincter
      during vaginal delivery may lead to the development of stress urinary
      incontinence. The purpose of this work was to study the consequences of pregnancy
      and childbirth on urinary problems. STUDY DESIGN: An inception cohort of 368
      consecutive women suffering from multiple sclerosis (MS), according to the Poser
      criteria, were included in the study between June 1999 and June 2000. For each
      patient a full urological and obstetrical record was obtained. RESULTS: Two
      hundred and seventy-three women (74%) had had at least one pregnancy. The parous
      women were older at the time of the study (mean age: 45.5 years vs 35.5 years),
      and were older at MS onset (mean age: 32.8 years vs 25.7 years). The nulliparous
      women were more rapidly disabled, with a shorter time to reach an EDSS score of 3
      from MS onset (mean time of 5.9 years versus 8.2 years in parous women). In
      parous women, 259 (95%) had had at least one vaginal delivery and 14 (5%) had had
      a caesarean only. Delivery modalities had no influence on urinary disorder
      frequency or the type of problems. CONCLUSION: On the basis of these data, there
      is actually no clear argument for systematically performing caesarean section in
      MS women. Urinary disorders in these women were mostly linked to the duration and
      the severity of the disease but not to pregnancy or delivery modalities. From our
      point of view, caesarean section must be decided only on classic obstetrical
      criteria as for healthy women independently of multiple sclerosis. However our
      data were open and retrospective.

PMID- 17211969
TI  - Screening of foetal distress by assessment of umbilical cord lactate.
AB  - PURPOSE OF INVESTIGATION: Studies on umbilical cord blood for determination of
      lactate indicate that high levels seem to be correlated to foetal metabolism for
      anaerobic glycolysis taking place in oxygen-deprived tissues of the foetus. These
      findings may be of particular-deprived clinical importance when foetal distress
      or foetal hypoxemia is caused by perinatal events. METHODS: The maternal and
      foetal heart rates, acid-base values measured and the outcome of 94 pregnancies
      complicated by intrapartum foetal asphyxia have been reviewed, and the maternal
      and foetal acid-base and lactate levels during the course of labour and at
      delivery were studied in patients with evidence of metabolic acidosis. Lactate
      concentrations were measured during labour and at delivery in blood samples
      obtained from the foetal presenting part and from the umbilical cord with the use
      of a rapid electrochemical technique. The foetuses were evaluated by means of the
      Apgar score, intrapartum cardiotocography, observation of the presence of
      meconium stained amniotic fluid, and clinical features of distress at birth.
      RESULTS: Evidence of clinical foetal distress was not related to the severity of
      the asphyxia. An increased lactate level was found in asphyctic infants and a
      clear correlation between lactic acidosis and foetal distress was documented. Low
      Apgar scores were observed in infants with moderate or severe asphyxia at
      delivery. Scalp lactate correlated significantly with umbilical artery lactate,
      but not with 1-min or 5-min Apgar scores. The lactate concentration was higher in
      cases of instrumental delivery compared to spontaneous delivery. No perfect
      correlation was found between lactate level and neonatal outcome but there were
      not a significant number of neonates with immediate complications. The rate of
      forceps delivery in the distress group was significantly higher than that of the
      healthy foetuses, so spontaneous labour was less frequently associated with
      foetal distress than instrumental delivery. In the distress group, severe
      variable decelerations were generally recorded in the second stage of labour. The
      incidence of neonatal Apgar score < or = 7 in neonates with abnormal baseline
      foetal heart rate (FHR) was higher than in those with severe variable
      decelerations, mild variable decelerations, and transient tachycardia. Duration
      of the active second stage of labour was significantly with the presence of
      foetal lactate at the time of crowning of the foetal head and the presence of
      lactate in umbilical arterial and vein blood at delivery. Expulsion time > or =
      45 minutes, compared with shorter active second stage, and acidaemia at birth
      implied larger arterial-venous lactate differences. The presence of foetal
      lactate at crowning was also significantly associated with the level of umbilical
      arterial-venous lactate difference. CONCLUSION: Lactate and pH values provide the
      best parameters to distinguish between asphyctic and normal newborns, with
      lactate having the most discriminating power. The prospective value of the
      discrimination functions derived from lactate and pH data is good when the
      foetuses are allocated into normal parameters but poor when an attempt is made to
      allocate the foetuses into pathologic ones, with a high false-negative rate.
      However, the discriminating ability is improved when pathologic foetuses are
      included into one single abnormal group. These results confirm the potential use
      of rapid foetal blood lactate measurements for the early diagnosis of intrapartum
      foetal distress.

PMID- 17211970
TI  - Postoperative analgesia after cesarean section by continued administration of
      levobupivacaine with the On-Q Painbuster system over the fascia vs ketorolac +
      morphine i.v.
AB  - OBJECTIVE: This study aimed to detect if continuous local infusion of
      levobupivacaine with the On-Q Painbuster system provided postoperative analgesia
      of similar quality to morphine + ketorolac i.v. in patients undergoing cesarean
      section. MATERIALS AND METHODS: Using a randomized prospective double-blind
      study, 20 women undergoing cesarean section with a standardized spinal technique
      were randomly assigned into two groups to receive either 10 mg morphine + 120 mg
      ketorolac + saline solution up to 96 ml with an elastomeric pump i.v. (group A)
      or local infusion of levobupivacaine 0.2% with the On-Q PAINBUSTER system (group
      B). Both groups were administered ketorolac i.v. in bolus in case of pain.
      RESULTS: The two groups differed in their VAS scores with group A experiencing
      significantly less pain than group B; the consumption of analgesics was
      significantly lower in group A than in group B. CONCLUSIONS: The i.v. system with
      morphine and ketorolac is more effective than levobupivacaine subcutaneous
      infusion in reducing postoperative pain associated with cesarean section.

PMID- 17211971
TI  - Combined administration of misoprostol in the first and second trimester missed
      abortion cases.
AB  - OBJECTIVE: We aimed to investigate the effectiveness and adverse effects of
      combined (vaginal + oral) administration of misoprostol in missed abortion cases.
      MATERIAL AND METHODS: 48 missed abortion cases between 8 and 20 weeks of
      gestation were enrolled in this study. Misoprostol-induced medical abortion was
      planned; the first dose (200 microg) was administered intravaginally and
      subsequent doses (200 microg each) orally every following hour. A maximum of six
      doses (1200 microg) were used. Revision curettage was performed on all subjects
      who aborted. RESULTS: The mean time interval from the first dose of misoprostol
      until the abortion was 6.27 +/- 3.02 hours. The success rate was 95% for the
      whole group. We observed misoprostol-related trembling in one patient and fever
      in two patients. CONCLUSION: We believe that our low-dose combined misoprostol
      protocol is a safe, effective and well-tolerated method with minimal adverse
      effects for the termination of both first and second trimester pregnancy losses.

PMID- 17211972
TI  - Magnetoencephalography and magnetocardiography in neonates. Our experience in
      Greece.
AB  - This study reports our experience in the application of magnetoencephalography
      (MEG) and magnetocardiography (MCG) in neonates. Results gained from our studies,
      lead us to believe that MEG and MCG could provide clinical practice with non
      invasive, rapid and easy to perform methods, which could be adjuncts to
      conventional methods for the evaluation of neonatal brain and heart function.

PMID- 17211973
TI  - Effect of tibolone on cytochrome c oxidase I, beta-2-microglobulin and vascular
      endothelial growth factor gene expression in the lower urinary tract of castrated
      rats.
AB  - INTRODUCTION: The objective of this study was to evaluate the effect of tibolone
      on cytochrome oxidase I (COX I), beta-2-microglobulin (B2M) and vascular
      endothelial growth factor (VEGF) gene expression in the lower urinary tract of
      castrated rats. These genes are related to cell energy, cellular immunity and
      vascularization processes. METHODS: Fifty adult castrated rats remained at rest
      for 28 days. Thereafter they were randomly divided into two groups of 25 animals
      each. The lower urinary tract (bladder and urethra) was extracted in animals of
      one group and the other group received tibolone at a dose of 0.25
      microg/animal/day for another 28 days followed by removal of the lower urinary
      tract. Total RNA was extracted from animals of both groups, forming two pools.
      After RT-PCR (reverse transcriptase polymerase chain reaction), expression of COX
      I, B2M and VEGF genes was evaluated by agarose gel electrophoresis, visualized by
      UV illumination. RESULTS: Expression of the three genes (COX I, B2M and VEGF) was
      greater in the group treated with tibolone. CONCLUSION: The use of tibolone
      increases the expression of COX, B2M and VEGF genes in the lower urinary tract as
      compared with that in castrated rats.

PMID- 17211974
TI  - Maternal zinc and cord blood zinc, insulin-like growth factor-1, and insulin-like
      growth factor binding protein-3 levels in small-for-gestational-age newborns.
AB  - PURPOSE: To determine the relationship between maternal serum zinc (Zn) levels
      and birth weight of the offspring and their correlation with cord blood Zn,
      insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein
      3 (IGFBP-3) levels. METHOD: 22 term small-for-gestational-age (SGA) and 34 term
      appropriate-for-gestational-age (AGA) infants and their mothers were included.
      Maternal and cord blood Zn levels and cord blood IGF-1 and IGFBP-3 levels were
      measured. RESULTS: Eighteen percent of mothers had Zn deficiency (< 75 mcg/dl).
      No significant difference between IGF-1 and IGFBP-3 levels and birth weight of
      infants of the mothers with and without Zn deficiency was found. Maternal and
      neonatal Zn levels correlated (r = 0.38, p < 0.01). Mean IGF-1 and IGFBP-3 levels
      were significantly lower in the SGA group compared to the AGA group (42.3 +/-
      16.8 ng/ml, 1.2 +/- 0.2 mcg/ml, and 62.4 +/- 22.7 ng/ml, 1.5 +/- 0.4 mcg/ml, p <
      0.001). A correlation was found between birth weight, IGF-1 and IGFBP-3 levels,
      and weight gain of the mother during pregnancy (p < 0.01). CONCLUSIONS: Zn
      deficiency was not observed to be a risk factor for low birth weight. The
      significant difference between the SGA and AGA babies' IGF-1 and IGFBP-3 levels
      emphasizes function of the IGF system in intrauterine growth.

PMID- 17211975
TI  - Non-immune foetal hydrops: a case report.
AB  - Foetal hydrops occurs when a certain amount of interstitial fluid, produced by
      capillary ultrafiltration, overcomes the amount of interstitial fluid that
      returns to the blood circulation through the lymphatic system. Hydrops is
      classified as immune (IH) due to the presence of circulating maternal antibodies
      against the foetal red blood cell's antigens, and non-immune (NIH) that includes
      all the other causes of hydrops. This classification is still valid, but only
      under a clinical point of view because they differ in aetiology and management.
      In this article the management of a case of non-immune foetal hydrops is
      described, in which, unlike most other cases of non-immune foetal hydrops, the
      foetus survived.

PMID- 17211976
TI  - Transient bone marrow oedema of the femoral head in pregnancy--case report.
AB  - We report a case of transient oedema of the femoral head without signs of
      osteoporosis, and with spontaneous resolution after delivery. Magnetic resonance
      imaging is essential to differentiate between a traumatic necrosis and bone
      marrow oedema.

PMID- 17211977
TI  - MRI investigation for neurofibromatosis type 1 lesions during pregnancy--a case
      report.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder of the nervous
      system that causes tumor growth on the nerves, skin changes and bone deformities,
      and it is reported to be associated with adverse perinatal outcome in pregnant
      women. CASE: We report a case of MRI investigation of a pregnant woman with a
      known NF1 disease who showed exacerbation of skin lesions during pregnancy. No
      dangerous lesions that could compromise pregnancy outcome were detected, thus
      allowing the pregnancy to continue to term uneventfully. CONCLUSION: MRI has
      strong indications for the follow-up of pregnant patients with neurofibromatosis
      as it can detect lesions that can serve as risk factors for pregnancy
      complications.

PMID- 17211978
TI  - Inguinal dermoid cyst of the round ligament. A case report and review of the
      literature.
AB  - INTRODUCTION: Dermoid cysts are rarely located in extraovarian sites,
      representing an extremely uncommon lesion of the round ligament. The differential
      diagnosis of an inguinal lesion that proved to be a dermoid cyst deriving from
      the round ligament is presented with a review of the literature. CASE REPORT: A
      case of a 27-year-old female with a dermoid cyst arising from the round ligament
      and lying inside the inguinal canal, which was tender and palpable, is reported.
      DISCUSSION: Underlining their origin, clinical manifestation, gross appearance
      and pathology, we differentiate dermoid cysts mainly from epidermoid cysts and
      mature cystic teratomas, analyzing the importance of such a distinction to the
      possibility of malignant degeneration and recurrence of a dermoid cyst in the
      round ligament.

PMID- 17211979
TI  - Alcohol concentrations in post-mortem body fluids.

PMID- 17211980
TI  - Platelet activation, upregulation of CD11b/ CD18 expression on leukocytes and
      increase in circulating leukocyte-platelet aggregates in Indian women chronically
      exposed to biomass smoke.
AB  - The majority of households in rural India still rely on unprocessed solid biomass
      for domestic energy. The aim of this study was to investigate whether chronic
      exposure to biomass smoke causes activation of leukocytes and the formation of
      leukocyte-platelet aggregates. We conducted flow cytometric analysis of beta2 Mac
      1 integrin (CD11b/CD18) expression on polymorphonuclear leukocytes (PMN) and
      monocytes, and P-selectin (CD62P) expression on the platelets of 165 women from
      eastern India, who cook solely with wood, dung and agricultural wastes, and 155
      age- and socio-economic condition-matched control subjects, who used relatively
      cleaner fuel, liquefied petroleum gas (LPG). Leukocyte-platelet aggregates were
      defined as CD11b-positive PMN and monocytes co-expressing platelet-specific
      markers CD41 or CD62P. A significant increase in leukocyte-platelet aggregates
      was found in women who used biomass as cooking fuel. In addition, they showed
      increased surface expression of CD11b/CD18 in circulating PMN and monocytes and
      CD62P expression on platelets. The mean fluorescence intensity (MFI) of CD11b on
      the surface of circulating monocytes and PMN of biomass users increased by 50 and
      68%, respectively. Similarly, a 62 and 48% increase in MFI was observed in CD18
      expression on the surface of these cells in biomass users. The results show that
      chronic biomass smoke exposure activates circulating platelets, PMN and
      monocytes, and increases the number of leukocyte-platelet aggregates, which are
      considered a risk factor for thrombosis.

PMID- 17211981
TI  - Environmental lead exposure and its relationship to traffic density among
      Senegalese children: a cross-sectional study.
AB  - Leaded-gasoline is probably the primary source of lead (Pb) exposure in Dakar
      (Senegal). The present cross-sectional study was undertaken to investigate the
      levels of Pb in Senegalese children and to present helpful data on the
      relationship between Pb levels and changes in biological markers of heme
      biosynthesis and oxidative stress. A total of 330 children, living since birth
      either in rural or urban areas (ie, Khombole (n = 162) and Dakar (n = 168),
      respectively) were included. During this cross-sectional study, the mean blood
      (B)-Pb level in all children was 7.32 +/- 5.33 microg/dL, and was influenced by
      the area of residence and gender. In rural children, 27 subjects (16.7%), 18 boys
      (19.6%) and nine girls (12.9%), had a B-Pb level > 10 microg Pb/dL, whereas 99
      urban children (58.9%), respectively, 66 boys (71.8%) and 33 girls (43.4%), had
      alarmingly high B-Pb levels. Accordingly, urine delta-aminolevulinic acid levels
      were higher in children living in the urban area than in the rural areas (P <
      0.001), and closely correlated with the B-Pb levels (P < 0.01). Moreover,
      glutathione peroxidase (GPx) activity, selenium (Se) level, glutathione reductase
      (GR) activity, and glutathione status were significantly influenced by area of
      residence and/or by gender. GPx activity and Se level were not only negatively
      correlated with B-Pb levels, but also positively correlated together (P < 0.01).
      Taken together, the present results allow us to conclude that urban children have
      higher B-Pb levels than rural children, and that of these children, boys have
      higher B-Pb levels than girls, leading thereby to alterations of heme
      biosynthesis and pro-oxidant/antioxidant balance. We also suggest that exposure
      to Pb and the Pb-induced adverse effects merits attention and that the
      development of preventive actions are of increasing importance in Senegal.

PMID- 17211982
TI  - Should all patients with unexplained anaemia be screened for chronic lead
      poisoning?
AB  - The global prevalence of lead poisoning is declining. However, the prevalence of
      lead poisoning in patients with either microcytic or normocytic anaemia is
      unknown. Blood samples from anaemic patients residing in south-east London
      without an obvious cause for anaemia had their blood lead concentration (BLC)
      analysed. A batch of 988 samples was analysed for BLC using atomic absorption
      spectroscopy. Median haemoglobin was 10.3 g/dL (range: 4.2-10.9) in females, 10.6
      g/dL (range: 5.2-11.4) in males and 10.7 g/dL (range: 6.7-10.9) in children.
      Median BLC was 2.63 microg/dL (0.21-24.0 microg/dL; 95th centile 7.54 microg/dL).
      Fifteen samples (1.5%) had a BLC > 10.0 microg/dL, five samples (1%) > 15.0
      microg/dL and one sample (0.1%) > 20.0 micrg/L. In the 106 children, median BLC
      was 2.34 microg/dL (0.5-14.5 microg/dL; 95th centile 6.12 microg/ dL). Only one
      child (14.5 microg/L) had a BLC > 10.0 pg/dL. There was a poor correlation
      between haemoglobin and BLC (r2 = 0.08). Routine screening for lead poisoning
      cannot be justified in all patients with unexplained anaemia, unless there is a
      history or clinical features to suggest lead toxicity. Additionally, we have
      shown that in this former high-risk area for lead exposure, there is a low point
      prevalence of significant lead poisoning, even in an anaemic population.

PMID- 17211983
TI  - Effects of organochlorine pesticides on interleukin secretion from lymphocytes.
AB  - Organochlorine pesticides have been used worldwide primarily as insecticides. Due
      to their chemical stability, they often persist in the environment long after
      their use has ceased. In a previous study, we found that six organochlorine
      compounds (alpha-chlordane, gamma-chlordane, 4,4'-DDT, heptachlor, oxychlordane,
      and pentachlorophenol (PCP)), at concentrations of 5 microM, were able to
      significantly decrease the ability of highly purified human natural killer (NK)
      cells to lyse tumor cells after exposures, ranging from 1 hour to 6 days.
      However, if T cells were present with the NK cells (T/NK cells), loss of lytic
      function was seen only with oxychlordane and PCP. The purpose of the current
      study is to begin to investigate the mechanism by which T cells may be blocking
      the negative effects of some organochlorine compounds on NK cell function. Here,
      we investigated the hypothesis that T cells could produce significant levels of
      NK-stimulatory interleukin(s) (ILs), and that this may account for the decreased
      inhibition seen with organochlorine exposures when T cells were present.
      Secretion of four cytokines that have a demonstrated capacity to influence NK
      function, and/or are secreted by T cells, was measured (IL-2, IL-4, IL-10, IL
      12). We measured both the baseline levels of ILs and the effects of
      organochlorine compound on IL secretion in T/NK cells. The results showed that
      baseline levels of the NK-stimulatory IL, IL-12, were 898 +/- 264 pg/mL at 24
      hours and IL-10 levels were 564 +/- 337 pg/mL. In contrast, IL-2 levels were 14
      +/- 10 pg/mL, and IL-4 levels were 3 +/- 2 pg/mL at 24 hours. The two compounds
      that retained their capacity to decrease NK lytic function in T/NK cells,
      oxychlordane (5 microM) and PCP (5 and 10 microM), were able to either decrease
      the secretion of NK-stimulatory ILs (IL-2, IL-12 and/or IL-10) and/or increase
      secretion of the NK-inhibitory cytokine, IL-4, at each length of exposure tested.

PMID- 17211985
TI  - Arsenic-induced toxicity: effect on protein composition in sciatic nerve.
AB  - Exposure to arsenic compounds may lead to skin and lung cancer and various
      disorders such as vascular disease and peripheral neuropathy in humans.
      Peripheral arsenic neurotoxicity has been demonstrated clinically and in
      electrophysiological studies. Patients intoxicated with arsenic show neurological
      symptoms in their feet and hands. These patients show significantly lower nerve
      conduction velocities (NCVs) in their peripheral nerves in comparison with
      controls. The mechanism of arsenic peripheral nervous system (PNS) toxicity,
      however, has never been described before. This is the first study to investigate
      the toxicity of arsenic on the PNS. Male Wistar rats were exposed to arsenite
      given as a single dose i.v. After sacrifice, sciatic nerves were excised and the
      protein composition was analysed. Protein analysis of sciatic nerves showed
      disappearance of neurofilament and fibroblast proteins in rats treated with
      arsenite doses of 15 and 20 mg/kg in comparison with the control groups. Some
      fibroblast protein bands had disappeared in the 20-mg/kg dose group. The analysed
      neurofilament-M and -L proteins decreased dose dependency over time. arsenic
      affects the composition of proteins in the rat sciatic nerve, especially the
      neurofilaments. The reduction of signals in Western blot analysis reveals changes
      in cytoskeletal composition, which may well lead to neurotoxic effects in vivo.

PMID- 17211984
TI  - Effect of lead exposure on serum immunoglobulins and reactive nitrogen and oxygen
      intermediate.
AB  - Metal toxicants may affect immune regulation with an increased incidence of
      infectious diseases, cancer or autoimmune diseases. Lead is the leading
      environmental toxin among heavy metals and has aroused concern, as continuous low
      level exposure leads to a variety of health problems. We compared serum
      immunoglobulins (Ig) and reactive oxygen and nitrogen intermediates (super oxide
      and nitric oxide (NO)) in culture supernatant of lead-exposed (blood lead; Pb-B >
      10 microg/dL) individuals with that of unexposed healthy controls (blood lead <
      10 microg/dL). The serum IgA level was significantly increased in lead-exposed
      individuals in comparison to controls (182 +/- 53 versus 138 +/- 52 mg/dL; P <
      0.05). Furthermore, lipopolysaccharide-induced NO production by mouse macrophage
      cells, RAW 264.7, showed significant suppression (P < 0.05) after treatment with
      lead acetate (100 ppm). This study suggested that lead could modulate the immune
      system by targeting the humoral as well as innate immune cells.

PMID- 17211986
TI  - Cell cycle proteins in normal and chemically induced abnormal secondary palate
      development: a review.
AB  - Cell cycle progression and thus proper cell number is essential for normal
      development of organs and organisms. Craniofacial tissues including the secondary
      palate are vulnerable to disruption of cell cycle progression and proliferation
      by many chemicals including mycotoxin, secalonic acid D (SAD), glucocorticoids,
      retinoic acid and 2,3,7,8-tetrachlorodibenzodioxin. Induction of cleft palate
      (CP) by SAD in mice occurs from a reduction in the size of developing palatal
      shelves. This is associated with an inhibition of proliferation of murine and
      human embryonic palatal mesenchymal (MEPM and HEPM) cells as well as a G1/S block
      of cell cycle. In murine embryonic palates and HEPM cells, SAD inhibited G1/S
      phase-specific cyclin-dependent kinase (CDK)2 activity, reduced the level of
      cyclin E and increased the level of the CDK2 inhibitor, p21. These results,
      together with those from other laboratories, suggest that common cell cycle
      protein targets (biomarkers), relevant to the pathogenesis of CP by multiple
      chemical exposures, that can form the basis for the diagnosis and the development
      of preventive strategies, are likely to exist.

PMID- 17211987
TI  - Mortality related to cerebrovascular disease in systemic lupus erythematosus.
AB  - The objective of this study was to examine mortality rates related to
      cerebrovascular disease in systemic lupus erythematosus (SLE) compared to the
      general population. Our sample was a multisite Canadian SLE cohort (10 centres, n
      = 2688 patients). Deaths due to cerebrovascular disease were ascertained by vital
      statistics registry linkage using ICD diagnostic codes. Standardized mortality
      ratio (SMR, ratio of deaths observed to expected) estimates were calculated. The
      total SMR for death due to cerebrovascular disease was 2.0 (95% confidence
      interval [CI] 1.0, 3.7). When considering specific types of events, the category
      with the greatest increased risk was that of ill-defined cerebrovascular events
      (SMR 44.9 95% CI 9.3, 131.3) and other cerebrovascular disease (SMR 8.4, 95% CI
      2.3, 21.6). Deaths due to cerebral infarctions appeared to be less common than
      hemorrhages and other types of cerebrovascular events. Our data suggest an
      increase in mortality related to cerebrovascular disease in SLE patients compared
      to the general population. The large increase in ill-defined cerebrovascular
      events may represent cases of cerebral vasculitis or other rare forms of nervous
      system disease; alternately, it may reflect diagnostic uncertainty regarding the
      etiology of some clinical presentations in SLE patients. The suggestion that more
      deaths are attributed to cerebral hemorrhage, as opposed to infarction, indicates
      that inherent or iatrogenic factors (eg, thrombocytopenia or anticoagulation) may
      be important. In view of the paucity of large-scale studies of mortality
      attributed to neuropsychiatric outcomes in SLE, our findings highlight the need
      for additional research in large SLE cohorts.

PMID- 17211988
TI  - CAMP response element modulator a expression in patients with systemic lupus
      erythematosus.
AB  - T cells from patients with systemic lupus erythematosus (SLE) have high levels of
      cAMP response element modulator (CREM)-alpha which bind to the interleukin (IL-2)
      promoter and limit IL-2 production. In this case-controlled study, we show that
      CREM-alpha mRNA levels were higher in T cells from patients with SLE than
      controls while CREB mRNA levels did not differ between the two groups. CREM-alpha
      mRNA levels did not correlate with clinical characteristics, disease activity or
      treatment. Nevertheless, there was a trend for patients on high doses of
      corticosteroids to have low levels of CREM-alpha mRNA. The discovery of specific
      non-toxic medications that block the expression of CREM-alpha may prove useful in
      reversing the aberrant T cell function in SLE.

PMID- 17211989
TI  - Further description of early clinically silent lupus nephritis.
AB  - Thirty silent lupus nephritis (SLN) patients were compared to 16 individuals
      bearing overt lupus nephritis (OLN). Results included: years of systemic lupus
      erythematosus (SLE) diagnosis were significantly earlier (4.6 +/- 2.8 years) in
      SLN than in OLN (7.18 +/- 3.61) (P < 0.05). Neurological compromise,
      hypertension, normocitic anemia and lymphopenia were significantly prevalent in
      OLN than in SLN (P < 0.05). Beside normal urinary sediment and renal function
      tests, the SLN group showed a moderate increase of both activity (AI) and
      chronicity (CI) renal pathology index when compared to highly increased AI and CI
      in OLN (P < 0.05). Seventy percent of SLN patients were ISN/RPS Classes I (6.6%)
      and II (63.3%) while 81% of OLN cases were Classes III, IV (37.5%) and V. IgG,
      IgA, IgM, lambda chain, C3 and fibrinogen immune deposits were found in 90% or
      over in both SLN and OLN individuals while in 60% or over, both groups also
      showed kappa chain, Clq and C4 deposits. While prevalence of ANA, anti-dsDNA and
      anti-C1q antibodies were similar in both groups, anti-histone, anti-RNP, CIC and
      CH50 serum levels were significantly different in OLN versus SLN (P < 0.05). We
      strongly suggest that indeed SLN is the earliest stage in the natural history of
      lupus nephritis.

PMID- 17211990
TI  - Estrogen does not regulate CD154 mRNA stability in systemic lupus erythematosus T
      cells.
AB  - Previous studies in our laboratory showed a dose-dependent and hormone-specific
      increase in CD154 expression in T cells from females with systemic lupus
      erythematosus (SLE). This present study investigates if the estrogen-dependent
      increase in CD154 expression is due to stabilization of the messenger RNA. T
      cells from female SLE patients and controls were cultured for 18 h in serum-free
      medium without and with estradiol 17-beta (10(-7) M). T cells were either
      unstimulated (resting) or were activated by further culture on anti-CD3 coated
      plates. Actinomycin D (25 microg/mL) was added to parallel cultures to inhibit
      new messenger RNA synthesis. CD154 messenger RNA stability was assessed by
      reverse-transcription polymerase chain amplification. Resting SLE (n = 10, P =
      0.88) and normal (n = 7, P = 0.65) T cells showed no significant differences in
      message stability in response to estradiol. CD154 messenger RNA was also not
      significantly stabilized in activated SLE (n = 10, P = 0.15) or activated normal
      (n = 6, P = 0.077) T cells in response to estradiol. These findings indicate that
      the estrogen-dependent increase in CD154 in SLE T cells is not due to stability
      of the mRNA. These data are consistent with the postulate that estradiol
      stimulates CD154 transcription in SLE T cells.

PMID- 17211991
TI  - Stress as a predictor of cognitive functioning in lupus.
AB  - The objective of this study was to investigate the possible effects of the daily
      stress experienced during a six-month period on the cognitive functioning of
      patients with systemic lupus erythematosus (SLE). For this purpose, we evaluated
      the daily stress of 21 patients with lupus every day for six months. Later, we
      carried out a neuropsychological exam that included an evaluation of attention
      and memory. At the same time, scores on depression and anxiety were recorded with
      the objective of controlling other emotional variables that might be influencing
      these cognitive processes. The results show that daily stress was able to predict
      the scores on the neuropsychological variables studied. Specifically, the daily
      stress experienced in the previous six months is the variable with the greatest
      explanatory-predictive power on the scores for delayed recall visual memory,
      visual fluency and attention speed. This relationship proved to be negative in
      all three cases (R2 corr = 0.290; t = -2.712, P < 0.014); (R2 corr = 0.318; t = 
      2.818, P < 0.012); (R2 corr = 0.319; t = -2.906, P < 0.009), which means that the
      greater the daily stress, the lower the score on visual memory, fluency and total
      attention speed. We can state that daily stress is related to impairments in
      visual memory, fluency and attention in patients with SLE. This effect was not
      found with other emotional variables, such as depression and anxiety.

PMID- 17211992
TI  - Targeting human immunodeficiency virus type 1 with antibodies derived from
      patients with connective tissue disease.
AB  - During the budding process, human immunodeficiency virus (HIV) acquires several
      cellular proteins from the host. Thus, antibodies against self antigens found in
      sera patients with autoimmune disorders may cross react with host-derived or the
      HIV-specific proteins gp120 and gp41 on the viral envelope and probably
      neutralize HIV infection. To verify this hypothesis, 88 sera from HIV negative
      patients suffering from systemic lupus erythematosus (SLE) and other autoimmune
      disorders were analysed for cross reacting antibodies against HIV-1 by Western
      blot and FACS analysis indicating that antibodies cross-react with epitopes
      expressed on HIV infected or non-infected cells. Virus capture assays revealed
      that HIV-1(IIIB) was directly recognized by 60% of sera from patients with
      autoimmune disorders. Sera were also tested in HIV neutralization assays with
      stimulated T cells. Reduction of the viral load by patient sera correlated with
      their reactivity in Western blot analysis. Complement further enhanced the
      reduction of viral titres, although no complement-mediated lysis was observed.
      These data suggest a possible protective role of auto-antibodies against HIV
      infection in lupus patients.

PMID- 17211993
TI  - Aortic valve calcification in systemic lupus erythematosus.
AB  - Aortic valve calcification is associated with atherosclerosis in the general
      population. We investigated the prevalence of and associates of aortic valve
      calcification in systemic lupus erythematosus (SLE). One-hundred and ninety-nine
      SLE patients enrolled in a clinical trial had aortic valve calcification assessed
      by helical CT. The patients had a mean age of 44.3 +/- 11.4 years and were 92%
      female, 61% Caucasian, 34% African-American, 2% Asian and 2% Hispanic. Aortic
      valve calcification was present in 1.5%, whereas coronary calcium was found in
      43% and carotid plaque in 17%. Among cardiovascular risk factors, hs-CRP (P =
      0.0592), fibrinogen (P = 0.0507), and lipoprotein(a) (P = 0.0250), were
      associated with aortic valve calcification. Prednisone use (P = 0.049) and use of
      methotrexate (P = 0.0174) were also associated with aortic valve calcification.
      Aortic valve calcification was associated with antiphospholipid antibody
      positivity (0.0287) (lupus anticoagulant, by dilute Russell viper venom time). It
      was not associated with coronary calcium or carotid plaque. Aortic valve
      calcification, although rare in SLE, was associated with some novel
      cardiovascular risk factors and with a marker of hypercoagulability (lupus
      anticoagulant). In contrast to the general population, aortic valve calcification
      in SLE is not associated with subclinical measures of atherosclerosis, such as
      coronary calcium or carotid plaque.

PMID- 17211994
TI  - Treatment of menorrhagia associated with oral anticoagulation: efficacy and
      safety of the levonorgestrel releasing intrauterine device (Mirena coil).
AB  - Menorrhagia is common in women receiving oral anticoagulation. In healthy women,
      reductions of up to 90% of menstrual loss have been described with the
      levonorgestrel releasing intrauterine device (LNG-IUS). However there is no data
      about the use of LNG-IUS in women receiving oral anticoagulation and so we
      assessed the efficacy and safety of LNG-IUS in this setting. Patients with
      menorrhagia who used LNG-IUS and warfarin were contacted by post and asked to
      complete a questionnaire assessing the extent and duration of menstrual bleeding,
      quality of life and treatment satisfaction. The questionnaire was sent to 23
      patients and returned by 17. The amount of bleeding was reduced with the LNG-IUS
      in 10 (58.8%) women; amenorrhea occurred in four (23.5%), no change in blood loss
      in one (5.9%) and greater blood loss in two (11.8%) patients. The number of
      sanitary pads used was less in 12 (70.6%) patients; same in one (5.9%) patient,
      more in two (11.8%) patients and two (11.8%) did not remember. Five patients
      (29.4%) had shorter duration of bleeding, four (23.5%) had amenorrhoea, four
      (23.5%) had longer periods and four (23.5%) had same duration by subjective
      assessment. Eight (47.1%) patients felt very satisfied, four (23.5%) felt
      satisfied, two (11.8%) felt dissatisfied with the treatment, one felt very
      dissatisfied (5.9%) and two (11.8%) did not respond to the question. This small
      study suggests LNG-IUS is effective in reducing the duration and amount of
      menstrual bleeding in women with menorrhagia associated with oral
      anticoagulation. We feel the use of LNG-IUS is a major advance in reducing
      menorrhagia in women on oral anticoagulation as the previous alternative-
      hysterectomy--is associated with an increased risk of thrombosis and bleeding.

PMID- 17211995
TI  - Efficacy and safety of Etanercept, high-dose intravenous gammaglobulin and
      plasmapheresis combined therapy for lupus diffuse proliferative nephritis
      complicating pregnancy.
AB  - We report one case of pregnancy-onset severe diffuse proliferative nephritis in a
      patient with systemic lupus erythematosus (SLE), who was successfully treated
      with a combination of anti-tumour necrosis factor (TNF)-alpha, plasmapheresis and
      high-dose intravenous gammaglobulin. No flares were observed either in clinical
      symptoms or in laboratory examinations during pregnancy or after delivery. Her
      autoantibodies except fluorescent anti-nuclear antibodies were negative. We
      suggest that a combination of anti-TNF-alpha, plasmapheresis and high-dose
      intravenous gammaglobulin may be a safe and effective therapy for pregnant
      patients suffering severe lupus nephritis.

PMID- 17211996
TI  - Primary lymphoma of CNS, mycophenolate mofetil and lupus.
AB  - Lymphoproliferative disorders are known to complicate immunosuppressive therapy
      and two cases of primary lymphoma of CNS (PCNSL) have previously been described
      in association with mycophenolate mofetil (MMF) treatment. We report the third
      case of PCNSL in a patient with lupus nephropathy while on MMF treatment. PCNSL
      may be seen more frequently considering the increased use of MMF in
      immunosuppressant responsive conditions.

PMID- 17211997
TI  - Pregnancy-associated recurrent liver necrosis in patient with antiphospholipid
      syndrome.
AB  - The presence of antiphospholipid antibodies is associated with thromboembolic
      events, thrombocytopenia and numerous pregnancy complications such as recurrent
      miscarriage, preeclampsia and HELLP syndrome. This condition is known as the
      antiphospholipid syndrome (APS). We describe a rare case of recurrent liver
      necrosis postpartum in two consecutive pregnancies of woman with systemic lupus
      erythematosus (SLE) and positive antiphospholipid antibodies (aPL) who underwent
      complete recovery.

PMID- 17211998
TI  - Clinical and prognostic value of autoantibodies in puerto Ricans with systemic
      lupus erythematosus.
AB  - The aim of this study was to determine the association between lupus
      autoantibodies and the clinical manifestations and outcome in a cohort of Puerto
      Ricans patients with systemic lupus erythematosus (SLE). All patients fulfilled
      the American College of Rheumatology classification criteria for SLE. Demographic
      parameters, clinical manifestations over time and damage accrual were obtained at
      the last study visit. Disease damage was assessed with the Systemic Lupus
      International Collaborating Clinics Damage Index (SDI). ANA, ANA pattern, and
      anti-dsDNA, anti-Smith, anti-Ro (SSA), anti-La (SSB) and anti-snRNP antibodies
      were measured at the time of SLE diagnosis. Chi-square test, Fisher exact test,
      ANOVA, logistic regression and general lineal model analyses were used to
      evaluate these associations. Ninety-six percent of patients were females. The
      cohort had a mean age of 40.2 +/- 12.0 years and mean disease duration of 9.6 +/-
      7.0 years. Patients with elevated anti-dsDNA antibodies were more likely to have
      vasculitis, pericardial effusion, renal involvement, anaemia, leukopenia,
      lymphopenia and thrombocytopenia. Anti-Smith antibodies were positively
      associated with skin ulcerations, elevated liver enzymes, renal involvement and
      thrombocytopenia. Anti-Ro antibodies were related with the presence of discoid
      lupus, serositis, pneumonitis, elevated liver enzymes, hemolytic anaemia,
      leukopenia and lymphopenia. No positive associations were found for anti-snRNP or
      anti-La antibodies. The presence of anti-dsDNA, anti-Smith and anti-Ro antibodies
      was associated with higher SDI scores. In conclusion, anti-dsDNA, anti-Smith and
      anti-Ro antibodies are associated with several clinical manifestations and more
      damage accrual in Puerto Ricans with SLE. These findings provide valuable
      clinical and prognostic information for this ethnic population.

PMID- 17211999
TI  - Acute pan-dysautonomia: a rare initial presentation of lupus with sjogren's
      syndrome.

PMID- 17212000
TI  - Dermatomyositis with catastrophic pulmonary involvement.

PMID- 17212001
TI  - Bisphosphonates and atherosclerosis: why?

PMID- 17212002
TI  - Hepatitis C virus genotypes among HCV-chronic liver disease patients in Egypt: a
      leading trial.
AB  - In this trial, we have checked 50 anti-HCV positive, HCV-RNA PCR positive chronic
      liver disease cases, 44 males, 6 females with a mean age of 51 years. HCV-RNA
      extraction and genotyping was carried out at the Department of Medical
      Microbiology, University of Edinburgh, U.K. results showed that 47 (94%) of
      patients were of genotype 4 and 3 (6%) were of genotype 1. Liver biopsies were
      performed in 22 only out of the 50 patients studied. The 3 genotype 1 patients
      were biopsied, 2 had cirrhotic profile and one had CAH. Of 47 genotype 4
      patients, 19 were biopsied, 3 were CPH, 2 had CLH, 9 had CAH, 4 had cirrhosis and
      one patient had HCC. CONCLUSION: It appears that Egypt hosts predominantly HCV
      genotype 4 and less commonly genotype 1. This finding might have important
      implications concerning the epidemiological aspects, pathogenesis and response to
      antiviral therapy.

PMID- 17212003
TI  - Controlled trial with interferon alfa 2-b in chronic hepatitis C patients.
AB  - Thirty-eight chronic hepatitis C (CHC) Egyptian patients with persistently
      elevated serum alanine aminotransferase (ALT) for 6 months were randomly
      allocated into 2 groups: Group I (19 patients) received 3 million units (MU) of
      interferon alpha - 2b (Intron-A) subcutaneously thrice weekly for 6 months. In
      group I, complete response (normalization of ALT by the end of treatment) was
      achieved in 8 patients (42.1%), partial response (decrease of ALT by at least 50%
      of the pretreatment values) in 7 patients (36.8%) and no response in 4 (21.1%).
      Sustained response for 6 months after the end of therapy was attained in 4 of the
      8 (50%) complete responders. Thus attaining an overall sustained response in 4 of
      the 19 patients (21.1%). In group II, spontaneous normalization of ALT was
      established in 1 patient (5.3%). Repeat liver biopsies in 16 patients of the
      interferon group, revealed moderate improvement in the degree of lobular
      inflammation, hepatocyte necrosis and portal inflammation. We conclude from this
      study that treatment of CHC with 3 MU of IFN-alfa 2b thrice weekly for 6 months
      is associated with a low response rate (21.1%). To improve the results,
      escalation of the IFN dose and/or prolongation of the treatment period should be
      considered.

PMID- 17212004
TI  - Vector competence of autogenous and anautogenous Culex pipiens mosquitoes for
      Wuchereria bancrofti.
AB  - Vector competence of autogenous and anautogenous Culex pipiens; derived from
      North Sinai Governorate, Egypt, for the human filaria parasite Wuchereria
      bancrofti was studied. After feeding on the same microfilaremic volunteers both
      biotypes were readily infected with the parasite (infection rates > 80%) and
      supported its development to the infective stage within 11 - 12 days. Infective
      rates of both autogenous and anautogenous mosquitoes were similar (> 95%).
      However, autogenous Cx. pipiens developed significantly less number of infective
      stage larvae (4.7 +/- 1.4 L3 / female) than did anautogenous siblings (6.7 +/-
      3.6 L3 / female) (P < 0.05). Moreover, autogenous females were observed to
      contain twice the number of L3 larvae in the thoracic muscles and less larvae in
      the head region compared to autogenous counterparts. Vector competence
      characteristics of Cx. pipiens derived from a filariasis endemic area in Qalubiya
      Governorate were similar to those of anautogenous mosquitoes of North Sinai.
      These findings indicate that autogenous Cx. pipiens may be less efficient vector
      of W. bancrofti in endemic areas of Egypt.

PMID- 17212005
TI  - Genetic markers in coronary heart disease.
AB  - Coronary heart disease (CHD) was found to aggregate in families. So the present
      study aimed at studying certain genetic markers (lipoproteins, ABO blood groups
      and dermatoglyphics), in a group of 60 patients with CHD and a control group to
      detect any significant association between such genetics markers in this
      disorder. This can throw light on its genetics. The study revealed significant
      and marked association of CHD with low alpha-lipoprotein, high pre-beta and beta
      lipoproteins. No significant association wa detected with ABO phenotypes.
      Definite significant association was also detected between CHD and certain
      dermatoglyphics phenotypes including FTP, T-D count and palm patterns. These
      significant associations of CHD and these genetic markers "which are genetically
      determined" denoted strongly genetic etiology or at least genetic predisposition
      of CHD. Detection of such genetic markers may help in determination of risky
      individuals in population and families of CHD patients. This can help in
      prevention by proper genetic counseling.

PMID- 17212006
TI  - Residual renal function after living related kidney donation. Is it enough? An
      early report.
AB  - The utilization of living's kidneys as renal replacement for Chronic Renal
      Failure (CRF) patients was debated for long time. However, the lack of renal pool
      in one hand and the proper employment of modern investigatory armamentarium in
      another hand could justify such donation. Living related donors (LRD) are
      subjected to extensive non invasive investigations to assess their general
      fitness for donation and split renal function. The impact of uni-nephrectomy on
      the renal function was studied in 25 LRD. Serum Creatinine (S. Cr.) Creatinine
      Clearance (Cr. Cl.) and renographic clearance tests for total and split renal
      function and renal volume using ultrasound were determined before and 3 months
      after donation. An initial increase in s.cr was seen in 76% of donors, but all
      levels are within normal range. Total kidney function by cr.cl showed significant
      drop by 36% of the pre donated value. Remaining kidney clearance increased by 5%
      to 64% with an average of 34% of the pre donated level as measured by Tc 99m DTPA
      renography. Following nephrectomy, compensatory hypertrophy of the remaining
      kidney attributed to an increase in the renal volume of 15%. In conclusion,
      kidney donation from living's is safe. Cr. clearance using the chemical method is
      a good screening test for potential LRD and for monitoring the renal function
      after donation. Renographic clearance using Tc 99m DTPA is as excellent useful
      test for split renal function in LRD work up. Long-term follow up might be
      needed.

PMID- 17212007
TI  - Antepartum and postpartum depression and infant feeding pattern: a prospective
      study.
AB  - Mother's depression during pregnancy and postpartum is a risk factor that can
      adversely affect mother's relationship with her infant. As breast feeding is an
      important situation for early mother-child interaction the effect of mother's
      depression on her breast feeding attitude and practice was decided to be studied
      prospectively. In this study, 158 primigravidae attending antenatal clinics in
      two MCH centres were interviewed at third trimester. The interview data covered
      social background, attitudes to breast feeding as well as self rating of
      depression using the Edinburgh Postnatal Depression Scale (EPDS). At postnatal
      interview 72 mother-infant pairs could be reached between 6-16 weeks after birth.
      They were subjected again to EPDS along with inquiry about type of infant feeding
      and breast feeding practices. Findings revealed that the prevalence of antepartum
      depression was 25.32%. Antepartum depression was significantly linked to
      postpartum depression and negative attitudes to breast feeding. Persistent
      maternal depression (ante- and postpartum) was a risk factor for early resorting
      to mixed infant feeding, retarded infant growth as well as some adverse maternal
      and infant health outcomes. Logistic analysis indicated that negative mothers'
      attitudes to breast feeding and postpartum depressive scores taken together
      predicted mixed infant feeding. Hence, preventive programs should be directed
      specifically towards modifying the mother's psychological status and her attitude
      on behalf of her infant.

PMID- 17212008
TI  - Occupational dermatoses among workers in a porcelain manufacturing factory.
AB  - The objectives of the present work are to determine the prevalence and risk
      factors of occurrence of occupational dermatoses among workers in a porcelain
      manufacturing factory. The study included 235 workers (132 males and 103
      females). After history taking, dermatological examination was performed at the
      work place. Cases of contact dermatitis (CD) were patch tested using potassium
      dichromate 0.5%, Cobalt chloride 1% and Nickel sulphate 5% in petrolatum. Results
      showed that the prevalence of occupational dermatoses (OD) was 26.8% among
      exposed workers. The highest percentage of OD was found among workers in the
      decoration department. It represented 30.2% of all cases. CD was the commonest
      presentation among the studied group, it represented 27% of all cases of OD.
      Results of patch testing indicated that out of 17 cases of CD 12 cases (70%) were
      of the irritant variety and 5 cases (30%) were of the allergic type. The
      prevalence of OD was found to be affected by age, duration of work, type of
      exposure and daily bathing after work.

PMID- 17212009
TI  - Workers knowledge of accidents' causes.
AB  - Accident constitutes a big problem of occupational health. It causes an economic
      loss to the work and worker. Six hundred workers were investigated by a well
      standardized questionnaire through interview. Most workers believed that the most
      important causes of accidents are those belonging to environment and work
      pattern. They did not know or denied that there are many important personal
      factors that are considered to be a corner stone in increasing accident rate.
      Ninety one percent of the investigated workers believed that the improper guarded
      machines are one of the most important causes of accidents, only 23% of the
      involved workers considered the psychological and social disturbance to cause
      accidents. It is concluded that there should be a well prepared program of health
      education to learn the workers the different causes of accidents and the methods
      to prevent and decrease the accident rates.

PMID- 17212010
TI  - Infant mortality rate at a selected urban, semi-urban and rural areas of Egypt,
      1992: a retrospective study.
AB  - A study of infant mortality rate (IMR) in Egypt in 1992 was conducted at three
      randomly selected areas representing different social classes. IMR per 1000 live
      births was ranged between 27.1 to 33.5. The differences between male and female
      IMR were markedly observed with no consensus amongst study areas. Neonatal
      mortality rate ranged between 4.7 to 11.1 while the post neonatal mortality rate
      ranged between 18.4 to 23.0. Diarrheal diseases were the most common cause of
      death amongst infants at all study areas, followed by respiratory illnesses.
      Inaccurate and under registration were noticed clearly in this work as observed
      from absence of neonatal deaths in rural areas. Also, in rural areas, prematurity
      was not recorded as a cause of death. Similarly, neonatal tetanus was not
      recorded as a cause of death at all study areas.

PMID- 17212011
TI  - Continuing medical education in primary health care in Saudi Arabia: an
      epidemiologic study of physicians' needs in the Asir region.
AB  - A cross sectional survey was carried out among doctors working in all the 238
      Primary Health Care Centers in the Asir Region, Southwestern Saudi Arabia using
      self administered questionnaire. The response rate was 90.1%. The highly needed
      aspects of clinical practice include emergency skills (82.3%), diagnostic skills
      (74.4%) and management of common diseases (65.2%). Aspects that rated low include
      physical examination techniques, prescription skills, history taking and
      referral. Areas in medicine that rated high on the doctors' list of needs include
      critical care (60.7%), obstetrics and gynecology (52.7%) and family and community
      medicine (52.8%). The most highly preferred means of fulfilling these needs
      include clinical rounds (73.2%), consultation with specialists (69.8%) and
      regular lectures (62.5%). The objective of establishing baseline data which are
      essential for future continuing medical education (CME) planning in the Asir
      region was achieved in this study. Based on the doctors needs, it was recommended
      that regional CME units be established and related organizations and institutions
      that will jointly plan a program of CME be identified.

PMID- 17212012
TI  - Effect of profenofos feeding on biochemical changes in chicken.
AB  - The disruption of transaminases and phosphatases from the normal values denotes
      biochemical impairment and lesions of tissues and cellular function because they
      are involved in the detoxification process, metabolism and biosynthesis of
      energetic macromolecules for different essential function. The results of the
      present study revealed that feeding chicken in profenofos contaminated feed at
      levels of 50, 100 and 200 ppm for three weeks, resulted in a significant increase
      in the values of glutamic-pyruvic transaminase (GPT), glutamic oxaloacetic
      transaminase (GOT), Alkaline phosphatase (A.P.) and cholesterol, especially at
      levels of 100 and 200 ppm. Upon return of normal feed free from profenofos for 10
      days, these values decreased gradually but not to normal and the decreases were
      not significant.

PMID- 17212013
TI  - Effect of profenofos feeding on food consumption, body weight and tissue residues
      in chickens.
AB  - Feeding chickens on profenofos contaminated food at levels of 50, 100 and 200 ppm
      resulted in significant decrease in food consumption and body weight with some
      mortalities in the third week of feeding. profenofos and its metabolites were
      found to distribute rapidly in the different tissues with a positive relationship
      between tissue residue levels and the corresponding feeding level tested. On
      return to normal food free from pesticide these residues dissipated rapidly from
      the different tissues.

PMID- 17212014
TI  - Adipocytokines and the expanding 'Asian Indian Phenotype'.

PMID- 17212016
TI  - Correlation of anemia, secondary hyperparathyroidism with left ventricular
      hypertrophy in Chronic Kidney Disease patients.
AB  - AIMS: To demonstrate the correlation of anemia and intact parathormone with left
      ventricular hypertrophy in a cohort of Chronic Kidney Disease (CKD) patients in a
      tertiary care centre. METHODS: A cross-sectional study was done over 2 years on
      230 renal failure patients (160 males, 70 females), aged 15-75 years, who had
      elevated serum creatinine and reduced GFR. The patients were assessed based on
      clinical history and a number of laboratory parameters including serum
      creatinine, calcium, iPTH level, Hb, Hct, GFR and LVMI. Settings : Patients were
      seen as inpatients and outpatients in a tertiary care centre. RESULTS: In CKD
      stages I, II and III, 51% of the patients had anemia Hb<11gm/dl), 16%of the
      patients had elevated iPTH, 79% of male patients and 71% of female patients had
      LVH. In Stage IV CKD, 55% of the patients had anemia, 25% of the patients had
      elevated iPTH, 74% of male patients and 100% of female patients had LVH. In stage
      V CKD, 76% of the patients had anemia, 31% of the patients had elevated iPTH, 77%
      of male patients and 96% of female patients had LVH. In all five stages, 78% of
      male patients and 71% of female patients with elevated iPTH had LVH, 81% of male
      patients and 90% of female patients with anemia had LVH. Systemic hypertension
      was present in 69% of the patients. CONCLUSION: Anemia is widely prevalent in our
      cohort of CKD patients. Severity of anemia is correlated to LVH and secondary
      hyperparathyroidism in these patients.

PMID- 17212015
TI  - Association of adipocytokines (leptin, adiponectin TNF-alpha), insulin and
      proinsulin with diabetes--the Mumbai Obesity Project [MOP].
AB  - Asian Indians have a unique phenotype characterized by increased abdominal
      obesity and visceral fat despite low body mass index [BMI]. Though studies have
      indicated some adipocytokines to be associated with diabetes and obesity in
      Indians, there are virtually no studies relating adipocytokines and proinsulin
      with diabetes and obesity in Asian Indians. In this study we looked at
      adipocytokines--leptin, adiponectin and tumour necrosis factor-a [TNF-alpha] and
      insulin and proinsulin in subjects with diabetes and obesity. Thirty five
      diabetic subjects and 50 healthy controls were recruited for the study. Leptin
      [p=0.002J and adiponectin levels [p=0.011] were lower and proinsulin values
      higher [p<0.001] in diabetic subjects compared to non-diabetic subjects. In
      addition, leptin [p<0.001] and proinsulin [p<0.001] were higher and adiponectin
      [p<0.001] lower, in obese subjects compared to non-obese subjects. TNF-alpha
      failed to show any significant difference between the study groups. Leptin and
      proinsulin showed a significant and positive correlation with BMI [p<0.001] and
      waist circumference [p<0.001]. Adiponectin showed an inverse correlation with BMI
      [p=0.050] and waist circumference [p=0.002]. Proinsulin showed a significant
      negative association with adiponectin [p=0.002]. Logistic regression analysis
      revealed leptin to be negatively associated [Odds ratio [OR]: 0.864, 95%
      confidence interval [95% CI]: 0.775 -0.963, p=0.008] and proinsulin [OR: 1.567,
      95% CI: 1.246-1.971, p<0.001] to be positively associated with diabetes even
      after adjusting for age, gender and BMI. Leptin [OR: 1.365, 95% CI: 1.170-1.592,
      p<0.001] and proinsulin [OR: 1.617, 95% CI: 1.218 -2.147, p=0.001] showed a
      significant positive association with obesity, while adiponectin [OR: 0.927, 95%
      CI: 0.865 - 0.995, p=0.035] had a significant inverse association. Linear
      regression analysis revealed that adiponectin is inversely associated with
      proinsulin even after the addition of age, gender and diabetes status [beta= 
      0.61, p=0.033] into the model. In conclusion, in urban Asian Indians in western
      India, proinsulin levels showed a positive association, while leptin and
      adiponectin showed a negative association with diabetes. With regard to obesity,
      leptin and proinsulin had a positive association, while adiponectin had a
      negative association. Proinsulin levels showed an inverse association with
      adiponectin indicating a possible link between insulin secretion and insulin
      resistance.

PMID- 17212018
TI  - Multiple colocutaneous fistulae.

PMID- 17212017
TI  - Accelerated platelet activation in Asian Indians with diabetes and coronary
      artery disease--The Chennai Urban Population Study (CUPS-13).
AB  - AIM: To assess platelet activation in south Indian type 2 diabetic subjects with
      and without CAD. METHODS: Four groups of subjects were studied; Group 1 comprised
      of non-diabetic subjects without coronary artery disease (CAD) (n = 30). Type 2
      diabetic subjects without CAD formed Group 2 (n = 30); Group 3 comprised of type
      2 diabetic subjects with CAD (n = 30) and Group 4 consisted of non- diabetic
      subjects with CAD (n=14). CAD was diagnosed based on coronary angiographic
      evidence of severe double or triple vessel disease. Platelet activation was
      tested after an overnight fast in blood obtained from a bleeding wound at 1
      minute post-incision (wound-induced activation) as well as venous blood
      stimulated in vitro with collagen, using whole blood flow cytometry. In subjects
      with CAD, aspirin was withdrawn for 7 days and nitrates for 24 hours. RESULTS:
      Collagen induced GP IIb/IIIa binding was significantly higher among diabetic
      subjects with (28.10 +/-19.89; p<0.05) and without CAD (21.02+/-19.62; p<0.05)
      and non-diabetic subjects with CAD (23.89+/-15.65; p<0.05) compared to non
      diabetic subjects without CAD (11.69+/-13.69). Regression analysis showed
      collagen induced GP IIb/IIIa binding to be significantly associated with CAD
      [odds ratio (OR): 1.029, p = 0.025] and diabetes (OR: 1.037, p = 0.007).
      CONCLUSION: Increased platelet activation is seen in urban south Indians with
      diabetes and CAD.

PMID- 17212019
TI  - Elephantiasis nostras: complication of third degree acid burn.

PMID- 17212020
TI  - Correlation between timing of ASV administration and complications in snake
      bites.
AB  - AIMS OF STUDY: The present study was undertaken to study the relationship between
      the time of anti-snake venom (ASV) administration due to late arrival of patient
      at hospital and subsequent development of complications. MATERIAL AND METHODS:
      All patients of snake bite that presented to our institution over a period of 1
      1/2 years were included in the present study. A detailed clinical history,
      clinical examination and investigations were carried out. The patients were
      administered ASV within 10 minutes of presentation. The bite to needle time (time
      between the bite and start of ASV) was noted. The patients were then followed up
      to note any subsequent development of complications. The end-point of the study
      was normalization of haematological and neurological parameters. RESULTS: Fifty
      patients became eligible for the study. Twenty patients (40%) had complications
      while remaining 30 patients (60%) were uncomplicated. An attempt was made to
      study relationship between bite to needle time and subsequent development of
      complications. It was found to be significant at 5% level of significance
      (p<0.05) by chi square test. CONCLUSION: Incidence of complications was directly
      proportional to the duration of venom in the blood prior to neutralization by ASV
      due to late arrival of patient at hospital. The early institution of ASV is
      beneficial in preventing complications however severe is the systemic
      envenomation.

PMID- 17212021
TI  - Diagnosing acid-base disorders.
AB  - Diagnosis and management of acid-base disorders ranks high among the medical
      problems that intimidate many physicians. In practice, acid-base disorders can be
      approached very systematically as they can be easily diagnosed when certain rules
      are applied. Using a four step process including, 1) determination the serum pH,
      2) calculation of the serum anion gap, 3) estimating the degree of compensation,
      4) calculation of the excess anion gap, the reader will be able solve any complex
      acid-base problem. In this review we describe a practical stepwise approach to
      identify and resolve issues involving acid-base disorders.

PMID- 17212023
TI  - Approach to a case of autonomic peripheral neuropathy.
AB  - Autonomic neuropathy is the term used to describe autonomic disturbances
      resulting from diseases of the peripheral autonomic nervous system. This is a
      group of disorders in which the small, lightly myelinated and unmyelinated
      autonomic nerve fibers are selectively targeted. Most often, autonomic
      neuropathies occur in conjunction with a somatic neuropathy (i.e. with motor
      weakness and/or sensory loss), but they can occur in isolation. Causes of
      autonomic neuropathies are immune-mediated, paraneoplastic, infectious, toxic and
      drug-induced, hereditary, nutritional and idiopathic. Amongst all, diabetes
      mellitus is the most common cause. Autonomic features, which involve the
      cardiovascular, gastrointestinal, urogenital, sudomotor, and pupillomotor
      systems, occur in varying combination in these disorders. Orthostatic hypotension
      is often the first recognized and most disabling symptom. Noninvasive, well
      validated clinical tests of autonomic functions along with a host of laboratory
      tests are of immense value to diagnose the presence and to demonstrate the
      distribution of autonomic failure. Treatment aims to treat specific cause of the
      autonomic neuropathy (if possible) and to control symptoms of autonomic
      dysfunction. Present review attempts to outline clinical approach to a case of
      autonomic peripheral neuropathy.

PMID- 17212022
TI  - Chikungunya.
AB  - Chikungunya fever is a viral disease transmitted to humans by the bite of
      infected Aedes aegypti mosquito. Like malaria and dengue, this infection has
      almost become endemic in India, especially central and south India. Symptoms of
      sudden onset of fever, chills, headache, nausea, vomiting, joint pain with or
      without swelling, low back pain, and rash are very similar to those of dengue
      but, unlike dengue, there is no hemorrhagic or shock syndrome form. Chikungunya
      is a self-limiting illness with no specific treatment. Travellers visiting
      endemic areas should be careful and take precautions to see that they are not
      bitten by mosquitoes.

PMID- 17212024
TI  - Viper bite with continuous defibrination despite adequate treatment with
      antivenom.
AB  - A case of envenomation due to viperine snakebite poisoning is presented. Patient
      showed continuous defibrination, without any other signs of poisoning, which
      could not be reversed with more than double the usual dose of polyvalent
      antivenom. This phenomenon could be due to envenomation caused by a snake,
      probably from Viperidae family, which is not covered by the polyvalent antivenom
      available in India.

PMID- 17212025
TI  - Hemichorea resulting from single enhancing computed tomography lesion.
AB  - A single small enhancing computerized tomographic lesion is a common finding in
      Indian patients with seizures, particularly focal seizures. A small single
      enhancing computed tomography lesion also presents with varied non-epileptic
      manifestations viz. focal neurological deficits, episodic vascular headache,
      syndrome of increased intracranial pressure, etc. Here we present a case of
      hemichorea resulting from single enhancing CT lesion. A 12-year-old female
      presented with acute onset abnormal movements involving right side of body. A
      clinical diagnosis of right hemichorea was made and patient was subjected to
      neuroimaging along with other investigations. CT scan showed a single ring
      enhancing lesion with perifocal edema in left thalamic area suggestive of
      neurocysticercosis. Patient was treated with albendazole, steroids and
      haloperidol therapy. Patient showed marked improvement at follow-up after one
      month. Repeat CT scan revealed resolution of lesion. This case has been reported
      because hemichorea in young female is usually caused by post-streptococcal
      infection and it is quite rare presentation of small ring enhancing lesion.

PMID- 17212026
TI  - Myelomatous pleural effusion.
AB  - Serous effusions in multiple myeloma are uncommon but a myelomatous pleural
      effusion occurring in these patients is extremely rare. Here we report a rare
      case of a 38 years lady who was diagnosed to have multiple myeloma and
      subsequently developed pleural effusion. The myelomatous nature of the effusion
      was first diagnosed on cytology and subsequently confirmed by a pleural biopsy.
      The pleural effusion showed an initial response to chemotherapy but subsequently
      recurred.

PMID- 17212027
TI  - Reversible cardiomyopathy.
AB  - We report a case of reversible dilated cardiomyopathy, in a middle-aged male. The
      patient presented with severe left ventricular dysfunction and atrial
      fibrillation. Inspite of vigorous medical therapy there was only mild clinical
      improvement. Subsequently laboratory test results diagnosed it as hyperthyroidism
      and then specific thyrostatic treatment was added. There was a prompt clinical
      and hemodynamic improvement in the form of reversal of left ventricular
      dysfunction and achievement of sinus rhythm at the end of two weeks.

PMID- 17212028
TI  - Cleistanthus collinus poisoning.
AB  - Cleistanthus collinus is an extremely toxic plant poison. Cleistanthin A and B,
      the toxins of Cleistanthus collinus, are diphyllin glycosides which produce
      cardiac arrhythmias, urinary potassium wasting, hypoxia, metabolic acidosis and
      hypotension. We report ARDS, distal renal tubular acidosis and distributive shock
      secondary to inappropriate vasodilatation in a case following ingestion of its
      leaves.

PMID- 17212030
TI  - Tropical spastic paraparesis from northern India.

PMID- 17212029
TI  - Medical philately (medical theme on stamps).

PMID- 17212031
TI  - Atypical presentations of Sheehan's syndrome.

PMID- 17212032
TI  - API expert consensus document on management of ischemic heart disease.

PMID- 17212033
TI  - Fifty ways to improve your life.

PMID- 17212034
TI  - Human genetics and politics as mutually beneficial resources: The case of the
      Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics during the
      Third Reich.
AB  - This essay analyzes one of Germany's former premier research institutions for
      biomedical research, the Kaiser Wilhelm Institute for Anthropology, Human
      Heredity and Eugenics (KWIA) as a test case for the way in which politics and
      human heredity served as resources for each other during the Third Reich.
      Examining the KWIA from this perspective brings us a step closer to answering the
      questions at the heart of most recent scholarship concerning the biomedical
      community under the swastika: (1) How do we explain why the vast majority of
      German human geneticists and eugenicists were willing to work for the National
      Socialist state and, at the very least, legitimized its exterminationist racial
      policy; and (2) what accounts for at least some of Germany's most renowned
      medically trained professionals' involvement in forms of morally compromised
      science that wholly transcend the bounds of normal scientific practice? Although
      a complete answer to this question must await an examination of other German
      biological research centers, the present study suggests that during the Nazi
      period the symbiotic relationship between human genetics and politics served to
      radicalize both. The dynamic between the science of human heredity and Nazi
      politics changed the research practice of some of the biomedical sciences housed
      at the KWIA. It also simultaneously made it easier for the Nazi state to carry
      out its barbaric racial program leading, finally, to the extermination of
      millions of so-called racial undesirables.

PMID- 17212036
TI  - [RAPD analysis on the germplasm resources of Gastrodia elata in Guizhou].
AB  - Genetic polymorphisms of genomic DNA of 15 samples from wild and culturaled
      Gastrodia elata Blume in Guizhou were analyzed by RAPD method. 12 effective
      primers are screened from 40 primers amplified a total number of 93 loci, among
      which 66 are polymorphic and the percentage of polymorphic loci (PPB) is 70.97%.
      UPGMA dendrogram analyzed by NTSYSpc, ver. 2.2 shows that Gastrodia elata have
      apparent genetic variance. Geological distribution and growing environment were
      significant factors for the polymorphism.

PMID- 17212035
TI  - Method as a function of "disciplinary landscape": C.D. Darlington and cytology,
      genetics and evolution, 1932-1950.
AB  - This article considers the reception of British cytogeneticist C.D. Darlington's
      controversial 1932 book, Recent Advances in Cytology. Darlington's cytogenetic
      work, and the manner in which he made it relevant to evolutionary biology, marked
      an abrupt shift in the status and role of cytology in the life sciences. By
      focusing on Darlington's scientific method--a stark departure from anti
      theoretical, empirical reasoning to a theoretical and speculative approach based
      on deduction from genetic first principles--the article characterises the
      relationships defining the "disciplinary landscape" of the life sciences of the
      time, namely those between cytology, genetics, and evolutionary theory.

PMID- 17212037
TI  - [Study on the dynamic change of flavonoids content in Mentha haplocalyx].
AB  - OBJECTIVE: To determine the dynamic change of total flavonoids and its main
      aglycone and glycoside content in Mentha haplocalyx Briq. METHODS: Using UV-VIS
      spectrum and HPLC method for the total flavonoids and its aglycone and glycoside.
      RESULTS: The accumulation of flavonoids showed a regular pattern. CONCLUSION: The
      contents of total flavonoids and its main aglycone and glycoside are highest in
      the traditional harvesting time.

PMID- 17212038
TI  - [Content deternmination of glycyrrhizic acid in cortex glycyrrhizae].
AB  - Glycyrrhizic acid content in Fen Gancao (barked licorice root) and its rough bark
      (Cortex Glycyrrhizae) was determined by HPLC. The result showed that at least
      three unknown ingredients were detected in Cortex Glycyrrhizae which were not in
      Fen Gancao, and glycyrrhizic acid content in the Cortex Glycyrrhizae is higher
      than that in Fen Gancao. It suggests that Cortex Glycyrrhizae can be used as the
      material not only to extract glycyrrhizic acid but also for making additives.
      Furtheronore, Fen Gancao should be further studied in order to reveal the
      differences of pharmacological effects between Fen Gancao and Licorice Root
      (Radix Glycyrrhizae).

PMID- 17212040
TI  - [Quantitative analysis on Radix Salviae miltiorrhizae by NIR].
AB  - OBJECTIVE: Rapid nondestructive determination of salvianolic acid B and
      tanshinone IIA in Radix Salviae Miltiorrhizae with near-infrared reflectance
      spectroscopy. METHOD: A quantitive model was built up with near-infrared diffuse
      reflectance spectroscopy. RESULTS: The RMSEP in quantitative calibration model
      for salvianolic acid B and tanshinone IIA were 0.259 and 0.0232 respectively.
      CONCLUSION: NIR technique can dispose the samples without complicated
      pretreatment. You can achieve the results rapidly and correctly. It owns many
      remarkable advantages that cannot be displayed by traditional analysis methods.
      It is qualified to rapidly analyze traditional Chinese medicine whose components
      are complex. NIR can control the quality in production process of traditional
      Chinese medicine.

PMID- 17212039
TI  - [Research on different processings of Scutellaria baicalensis Georgi].
AB  - OBJECTIVE: Comparing the different processings of S. baicalensis Georgi with
      fresh herb. METHODS: Watering, cooking and steaming method were adopted and the
      contents of flavonoids was determined by HPLC. RESULTS: Cooking and steaming
      method could not only intenerate the slices, but also destroy the activity of
      enzyme. So different means could be choosen according to practice. CONCLUSION:
      Among them, cooking method with 1 time volume of water, heating 10 min, drying at
      80 degrees C and steaming method taking 20 min, drying at 80 degrees C is proper.

PMID- 17212041
TI  - [Studies on HPLC-FPS of the saponins from Semen Ziziphi Spinosae].
AB  - OBJECTIVE: To establish a method of HPLC-fingerprint spectrum (HPLC-FPS) for the
      active part in Semen Ziziphi Spinosae (SZS) in order to control the quality of
      SZS from different places. METHODS: The gradient elution mode was applied in
      chromatographic separation, and data were analysed by" Similarity Evaluation
      software" to compare the HPLC-FPS of SZS from different places. RESULTS: The
      conditions for HPLC analysis of SZS were established and the FPS of samples from
      different habitats showed some differences. CONCLUSION: All components in the
      spectrum were separated well and the HPLC fingerprint method is repeatable. The
      method can be used in quality assessment of SZS.

PMID- 17212042
TI  - [HPLC-FPS establishment of Iris japonica Thunb].
AB  - Samples extracted from the root of Iris japonica Thunb were analyzed and the
      optimal HPLC chromatographic conditions was confirmed. Through analyzing the
      chromatography, the HPLC-FPS of Iris japonica Thunb was established.

PMID- 17212043
TI  - [Study on the sterols from a brown alga endophytic fungus (NO. ZZF36) from the
      South China Sea].
AB  - Four sterols were isolated from a brown alga endophytic fungus NO. ZZF36 from the
      South China Sea. Their structures were identified as brassicaterol(2),
      ergosterol(2), ergosterol peroxide(3),7,22(E)-ergostadiene-beta,5alpha,6beta
      triol(4) by spectroscopic methods.

PMID- 17212044
TI  - [Research of polysaccharide from Dioscorea opposita Thunb].
AB  - OBJECTIVE: To isolate a homogeneous polysaccharide RP from RDP (a crude
      polysaccharide from Dioscorea opposita Thunb.) , and study its preliminary
      composition and structure. METHODS: RP was obtained with water extraction,
      alcohol sedimentation, CTAB deprotein, cellulose column and SephadexG-100 column.
      The purities of RP were identified by SephadexG-200. PC analysis on its acidic
      hydrolysates was used to determine the sugar components. Sephadex chromatography
      was used to mensurate its molecular weight. IR was used to analysis RP. RESULTS:
      RP was homogeneous. IR indicated that RP had beta configurations. The compositon
      was identified by paper chromatography as glucose, D-mannose, D-galactose.
      CONCLUSION: The research could provide a theoretical foundation for further
      development and utilization.

PMID- 17212045
TI  - Structural characterization of a glucan isolated from Hedyotis diffusa Willd.
AB  - OBJECTIVE: To isolate a homogeneous polysaccharide RP from RDP (a crude
      polysaccharide from Dioscorea opposita Thunb.), and study its preliminary com
      position and structure. METHODS: RP was obtained with water extraction, alcohol
      sedimentation, CTAB deprotein, cellulose column and SephadexG-100 column. The
      purities of RP were identified by SephadexG-200. PC analysis on its acidic
      hydrolysates was used to determine the sugar components. Sephadex chromatography
      was used to mensurate its molecular weight. IR was used to analysis RP. RESULTS:
      RP was homogeneous. IR indicated that RP had P configurations. The compositon was
      identified by paper chromatography as glucose, D-mannose, D-galactose.
      CONCLUSION: The research could provide a theoretical foundation for further
      development and utilization.

PMID- 17212046
TI  - [Study on the chemical constituents of Sambucus chinensis Lindl].
AB  - OBJECTIVE: To study the chemical constituents of Sambucus chinensis Lindl.
      METHODS: The constituents were isolated and purified by various chromatographic
      methods and structurally identified by spectral analysis. RESULTS: 5 compounds
      were obtained as beta-sitosterol (I), oleanolic acid (II), ursolic acid (III),
      kaempferol-3-O-beta-D-(6-O-acetylglucopyranosid)-7-O-beta-D-glucopyranoside (IV),
      and kaempferol-3-O-beta-D-glucopyranosid-7-O-beta-D-glucopyranoside (V).
      CONCLUSION: The compound IV and compound V were obtained from these plants for
      the first time.

PMID- 17212047
TI  - [Studies on chemical constituents from Ligusticum glaucescens Franch].
AB  - OBJECTIVE: To study the chemical constituents from dry roots of Ligusticum
      glaucescens Franch. METHODS: Chromatography and spectrum analysis were employed
      to isolate and elucidate the chemical constituents in the plant. RESULTS: 4
      compounds were isolated and identified as levistolide A (I), ligustilide (II),
      pleuchiol (III) and ferulic acid (IV). CONCLUSION: I-IV were isolated from this
      plant for the first time. The work provided evidence for the exploitation and
      utilization of this plant resource.

PMID- 17212048
TI  - [Analysis on the volatile oil in Origanum vulgare].
AB  - OBJECTIVE: To analysis compositions of the volatile oil in Origanum vulgare.
      METHODS: GC-MS condition: using programmed temperature gas chromatography
      cinitial temperature was 60 degrees C, and then raising the temperature (5
      degrees C/min) to 240 degrees C, mass-to-electric charge ratio was 10 to 425.
      RESULTS: GC-MS identified 29 kinds of contents. CONCLUSION: Thymol and carvacrol
      are main compositions of the volatile oil in Origanum vulgare.

PMID- 17212049
TI  - [Study on amino acids from the fruit of Clausena lansium].
AB  - OBJECTIVE: To investigate the amino acids from the fruit of Clausenae lansium.
      METHODS: To determine the content of hydrolyzed and free amino acids from fresh
      fruit and dried fruit of Clausenae lansium by HPLC, 10 mmol/L Na2HPO4 (PB) was
      used as mobile phase (A) and PB-methanol-acetic acid (50:35:15) was used as
      mobile phase (B) on a Hypersil ODS column. RESULTS: 16 kinds of amino acids were
      assayed, 10 of all was necessary or half-necessary amino acids. The total content
      of free and hydrolyzed amino was 4.8 mg/g and 15.0 mg/g in fresh fruit; 4.8 mg/g
      and 15.0 mg/g in dried fruit. CONCLUSION: There are abundant amino acids in the
      fruit of Clausenae lansium.

PMID- 17212050
TI  - [Effect of shenkangwan on TGF-beta1 and FN in rat mesangial cells cultured by
      high glucose].
AB  - OBJECTIVE: To investigate the effect of Shenkangwan on secretion of transforming
      growth factor-beta1 (TGF-beta1) and Fibronectin (FN) and their mRNA expression in
      rat mesangial cells (MC)cultured by high glucose and explore its molecule
      mechanism on treating diabetic nephropathy (DN). METHODS: Rat MC were cultured in
      vivo and divided into six groups: low glucose group, high glucose group, normal
      rat serum group, Capoten tablets group, Shenkangwan high dose group and low dose
      group. Seventy two hours later, the secretion of TGF-beta1 and FN in MC were
      detected by enzyme linked immunosorbent assay (ELISA). The expression of TGF
      beta1, and FN mRNA were determined by semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: High gluscose could induce secretion
      of TGF-beta1 and FN in MC and increase expression of TGF-beta1 and FN mRNA. While
      Shenkangwan could repress these effects. CONCLUSION: Shenkangwan can suppress the
      secretion of the extracellular matrix in MC via TGF-beta1 signal way.

PMID- 17212051
TI  - [Determination of ginsenoside rd in human plasma by LC/MS/MS].
AB  - OBJECTIVE: To develop a HPLC/MS/MS method for the determination of ginsenoside Rd
      in human plasma. METHODS: Plasma samples were pretreated by solid phase
      extraction (SPE). Ginsenoside Rd (m/z 964.6-->m/z 767.5) and gentiopicrin (m/z
      374.1-->195.1) was detected by the positive electrospray ionization (ES+I)-MS
      method under multiple reaction monitoring (MRM) mode. RESULTS: The calibration
      curve of ginsenoside Rd in plasma was linear over the range of 3.00-5000.00
      ng/ml. The limit of quantitation was 3.00 ng/ml. The relative recovery was 81.01
      83.39%. The within-day and between-day RSDs were less than 15%. CONCLUSION This
      method is accurate, sensitive, and specific. It is suitable for the measurement
      of plasma ginsenoside Rd concentration.

PMID- 17212052
TI  - [Study on the Chinese herbal formula for treatment of vaginitis and the
      antimicrobial activity in murine models].
AB  - OBJECTIVE: To study on the various proportions of Radix Sophorae Flavescentis,
      Cortex Phellodendri, Fructus Cnidii and pericarp of Zanthoxylum bungeanum Maxim
      in the formulas, whose antimicrobial effects on E. coli, S. aureus, P. aeruginosa
      and C. albicans under different pH values were compared in vitro. METHODS:
      According to Chinese ancient proved recipe, the K-B method and plate diluting
      method were adopted to measure antimicrobial activity, and orthogonal design to
      ascertain the herbal formula in vitro. Finally, murine models were established to
      test the antimicrobial activity in vivo through vaginal membrane irritancy
      experiment, negative rate of pathogeny and pathological grade of vaginal
      membrane. RESULTS: The results suggested that formulas with different proportions
      of the herbs had diverse antimicrobial activities, and the effect was shown to be
      most obvious when one milliliter drug contains 100 microl Fructus Cnidii-pericarp
      of Zanthoxylum bungeanum (2:1) co-extracted volatile oil and 50 microl Radix
      Sophorae Flavescentis and Cortex Phenodendri ethanol extraction respectively
      under pH6. The antimicrobial effect of the formula, which hardly had any membrane
      irritancy, was better than Jie Eryin in vitro and vivo. CONCLUSION: The fromula
      has few components and better effect, and adaptation to the pH value of
      vaginitis. It is a promising alternative for gynecological diseases.

PMID- 17212053
TI  - [Effects of ligustrazine injection on lymph circulation in rats with acute
      microcirculation disturbance].
AB  - OBJECTIVE: To explore the interferential effect of ligustrazine injection (LI) on
      lymph circulation in rats with acute microcirculation disturbance (AMD). METHODS:
      Sixteen Wistar male rats were divided into experimental and control groups. AMD
      was done by Dextran 500 injection from jugular vein and effects of LI on lymph
      circulation were observed in these rats by lymphatology methods. RESULTS: During
      AMD phase, the contractility of mesenteric lymphatic (ML) , the intestinal lymph
      flux, lymphocytes out put were obviously decreased, and there was little
      monocytes in the lymph fluid, but the lymph fluid viscosity was increased. After
      treatment of LI, the contractility of ML, the intestinal lymph flux, lymphocytes
      out put was obvious increased. There was a lot of monocytes in the lymph fluid
      and the lymph fluid viscosity was decreased. There were signifcant difference
      compared with control group (P < 0.05). CONCLUSION: LI can influence the recovery
      of AMD though enhancing the contractility of ML and the transport function of
      lymph circulation and decreasing lymph fluid viscosity.

PMID- 17212054
TI  - [Effects of DSF on the NO system level in experimental rats of myocardial
      ischemia].
AB  - OBJECTIVE: To observe the effect of DSF on NO System in experimental myocardial
      ischemia model by ligating the cornary descending branch. METHODS: Wistar mice
      were divided into control group, model group, Danshen group and DSF group to
      observe the effect of DSF on variations of the NO system. RESULTS: Compared with
      model group, content of NO, NOS and cNOS in serum and muscle in DSF group were
      significantly increased (P < 0.05 [Chinese character: see text] P < 0.01). But
      there was no statisical difference on the content of iNOS (P > 0.05) compared
      with model group. The expression of cNOS mRNA was increased (P < 0.05).
      CONCLUSION: The mechanism of DSF in treating coronary is realized by improving
      the content of NO, the activity of NOS and expression of cNOS mRNA in myocardial
      tissue.

PMID- 17212055
TI  - [The evaluation criterions about Caco-2 cell model].
AB  - OBJECTIVE: To establish and evaluate the Caco-2 cell model. METHODS: Caco-2 cell
      model was evaluated by morphology feature, TEER alkaline phosphatase and the
      transport of Propranolol. RESULTS: The determined values were corresponding to
      the references. The integrality, permeability and the expression of alkaline
      phosphatase in the cell model were superior. CONCLUSION: The established Caco-2
      cell model can be used to study the absorption mechanism of oral administration
      drug.

PMID- 17212056
TI  - [Cytotoxic effects of three kinds of eye drops for Chinese herbal medicines on
      various cell lines in vitro].
AB  - OBJECTIVE: To study the cytotoxic effects of three kinds of eye drops on human
      cancer cells and normal cells. METHODS: Cytotoxic effects of Yuxingcao Eye Drop
      (YXC), Gegensu Eye Drop (GGS) and Shuanghuanglian Eye Drop (SHL) on 6 cell lines
      (CNE2, Glc-82, HRPE, Fibro, 3T3 and ECV-304) were assayed using MTF method. And
      cytotoxic efficacy was evaluated using fifty percent of inhibitory concentration
      (IC50). RESULTS: IC50 of YXC to human cancer cells CNE2 and Glc-82 were (11.5 +/-
      0.25) microl/ml and (24.0 +/- 0.8) microl/ml; to normal cells HRPE, Fibro, 3T3
      and ECV-304 were (18.0 +/- 3.5) microl/ml, (52.0 +/- 14.0) microl/ml, (17.5 +/-
      3.5) microl/ml and (17.5 +/- 1.3) microl/ml, respectively. IC50 of GGS to CNE2,
      Glc-82, ECV-304 cells were (9.8 +/- 2.3) microl/ml, (17.0 +/- 5.0) microl/ml and
      (10.5 +/- 0.95) microl/ml, respectively. Under the concentration of 100
      microl/ml, the average survival rates of HRPE, Fibro and 3T3 cells were 60.0%,
      87.8% and 58.2%, respectively. IC50 of SHL to CNE2, Glc-82 and HRPE cells were
      (18.9 +/- 5.0) microl/ ml, (23.9 +/- 0.6) micorl/ml and (113.9 +/- 25.6)
      microl/ml. At the concentration of 100 microl/ml, the average survival rates of
      Fibro, 3T3 and ECV-304 Cells were 89.6%, 77.2% and 74.7%. CONCLUSION: YXC has
      evident cytotoxicities to human cancer cells and normal cells. While, GGS and SHL
      has not obvious cytotoxic effects to normal cells.

PMID- 17212057
TI  - [Study on purification of Radix Paeoniae Alba by HPD100 macroporous resin].
AB  - OBJECTIVE: To set up the method for purification of paeoniflorin by HPD100
      macroporous resin. METHODS: With the adsorption ration and desorption rate of
      paeoniflorin as the evaluating quotas, the single factor test, orhogonal
      experimental designs and variance analysis were applied to optimize the
      manipulation parameters of macrporous resin. RESULTS: The HPD100 had the best
      adsorbive and separative properties to paeoniflorin. The applicable technology
      was as follows: the sample concentration was 0.5 g/ml, the maximum capacity for
      medicinal materials was 10 g/g, the current velocit was 2 BV/h, the eluting
      reagent was 30% ethanol (4 times the volume of bottle). CONCLUSION: HPD100 resin
      can be used in purify of Radix Paeoniae Alba successfully. The purity of
      paeoniflorin was above 30%.

PMID- 17212058
TI  - [Preparation and stability investigation of gastrodin dispersible tablets].
AB  - To prepare and optimize the gastrodin dispersible tablets by orthogonal design
      using the disintegration time as index. The quality of gastrodin dispersible
      tablets was evaluated by the initial stability test. The results showed that the
      disintegration time of optimized prescription formulation was 106s, i.e. L-HPC
      and CMS-Na was used by combining exterior and interior and the dissolution
      percent in vitro was obviously super to the conventional tablets. Moreover, the
      quality of the dispersible tablets was very well by stability test.

PMID- 17212059
TI  - Papua New Guinea certified polio-free--complacency threatens dreams of
      eradication.

PMID- 17212060
TI  - Parasitological and clinical efficacy of standard treatment regimens against
      Plasmodium falciparum, P. vivax and P. malariae in Papua New Guinea.
AB  - Resistance of Plasmodium falciparum (Pf) and P. vivax (Pv) to standard
      antimalarials is widespread in Papua New Guinea (PNG). The objective of the study
      was to assess the rate of clinical treatment failure (TF) and parasite resistance
      to amodiaquine (AQ), chloroquine (CQ) and quinine+sulfadoxine/pyrimethamine
      (Q+SP) for malaria in a rural health centre of the East Sepik Province. 179
      patients presenting with symptoms and signs of malaria and with Pf (144
      patients), Pv (18 patients), P. malariae (Pm) (7 patients) or mixed infection (10
      patients) were included. 86 were treated with AQ, 88 with CQ and 5 with Q+SP.
      21/179 patients (12%) were not cured or had a recrudescence of symptoms
      associated with parasitaemia in the 28 days following treatment, 14% after AQ,
      10% after CQ and 0% after Q+SP. The proportion of TF was higher (17%) when the
      analysis population included only the 108 subjects who had a complete follow-up,
      especially for failure with Pf following AQ treatment (26%). During the 28 days
      of follow-up, RII or RIII level of resistance in Pf was detected in 55% of the
      subjects treated with amodiaquine, 30% of those treated with chloroquine and 0%
      of those treated with quinine+SP. Of the Pv or Pm parasites only one Pv was found
      to be RII resistant to CQ in the 28-day test. In vitro resistance of Pf to CQ was
      higher than to AQ (50% versus 27% of 36 parasite samples that grew successfully).
      The level of TF and parasitological resistance to standard antimalarial drugs was
      lower in this area than in urban settings, where drugs are more easily available.
      AQ performed less well than CQ but the difference is likely to be due to the age
      of the users, ie, their level of immunity, AQ being the first-line drug for young
      children. These results provided support for the recent change in the policy for
      the standard treatment of uncomplicated malaria in PNG from AQ or CQ to the
      combination of AQ+SP or CQ+SP, a recommendation aimed at slowing down the spread
      of multidrug resistance.

PMID- 17212061
TI  - Malaria control in Papua New Guinea results in complex epidemiological changes.
AB  - With a renewed interest in large-scale malaria interventions, knowledge about the
      possible long-term effects of such interventions on the nature of malaria
      transmission is essential. We document complex changes in malaria epidemiology
      over the last 40 years associated with changing malaria control activities in
      Karimui, an isolated area in Papua New Guinea. An initially equal distribution of
      Plasmodium falciparum, P. vivax and P. malariae changed to currently 68% P.
      falciparum, after passing through a phase of transitory P. vivax dominance, when
      control started to fail. Initial drops in malaria prevalence proved difficult to
      sustain and present post-control levels are significantly higher than pre-control
      levels. The example of Karimui indicates that unsustained control can lead to
      changes in malaria patterns that may leave a population worse off.

PMID- 17212062
TI  - Ribotyping of Salmonella enterica serovar Typhi isolates from Papua New Guinea
      over the period 1977 to 1996.
AB  - The prevalence of typhoid in the Papua New Guinea (PNG) highlands region
      increased rapidly in the mid-1980s, and now remains endemic. In this study
      ribotyping has been used to examine the number and types of Salmonella enterica
      serovar Typhi strains present during the 1977-1996 period. The ribotyping banding
      pattern results were based on Cla I and Eco RV digests. The 57 PNG isolates were
      divided into 11 different ribotypes. Comparison of ribotypes using coefficient of
      similarity values revealed a diverse group of ribotypes. Several strains appear
      to be endemic in PNG For instance, ribotypes 1, 2 and 3 were most commonly found
      among PNG isolates and isolates with these ribotypes have been cultured over a
      period of at least 11 years (1985-1996). Ribotype 3 was also observed in isolates
      from Malaysia and Thailand. Also found in PNG were ribotypes 4, 5, 6, 7, 8, 9, 16
      and 17. The ribotyping suggests that serovar Typhi strains present in PNG include
      unique strains of serovar Typhi and also strains that are common to other
      countries.

PMID- 17212063
TI  - Syphilis serology testing: a comparative study of Abbot Determine, Rapid Plasma
      Reagin (RPR) card test and Venereal Disease Research Laboratory (VDRL) methods.
AB  - Blood from 2100 women attending the antenatal clinic of the Port Moresby General
      Hospital (PMGH) and the 9 Mile urban clinic of Port Moresby was tested for
      syphili using the laboratory-based Venereal Disease Research Laboratory (VDRL)
      syphilis serology test and two clinic-based syphilis tests, Abbot Determine and
      Abbot Syfacard-RR (Rapid Plasma Reagin (RPR) card test). The Abbot Determine and
      the Syfacard-R tests were compared with the VDRL test, the gold standard in this
      study. The validation test results of Determine versus VDRL were as follows:
      sensitivity 92.0%; specificity 94.6%; the predictive value of a positive test
      42.6%; and the predictive value of a negative test 99.6%. The validation tests
      for RPR versus VDRL were as follows: sensitivity 56.3% specificity 96.5%;
      predictive value of a positive test 41.2%; and the predictive value of a negative
      test 98.1%. The RPR test costs 3.5 kina (about one US dollar) a test, the VDRL
      less than 1 kina a test whilst the Determine test kit costs about 5 kina a test.
      When laboratory time, salaries and other supplies are costed the Determine test
      is expected to cost relatively much less. Our recommendation is that the
      Determine test be made available in areas of the country where VDRL is
      unavailable or where logistics do not allow for test results to be available
      early enough to make a difference to the care of th pregnant woman and her fetus.

PMID- 17212064
TI  - Betelnut chewing: a contributing factor to the poor glycaemic control in diabetic
      patients attending Port Moresby General Hospital, Papua New Guinea.
AB  - This descriptive study was conducted in the Diabetes Clinic of the Port Moresby
      General Hospital for 6 months, from July to December 2002. The aim was to
      document the usage and effects of betelnut chewing in diabetic patients. 210
      patients were randomly selected from the list of patients in the appointment
      book, using a random number table. Betelnut chewing caused hyperglycaemia and
      diabetes mellitus in animal models. It was significantly associated with high
      fasting capillary blood glucose and was an independent risk factor for type 2
      diabetes mellitus. In this study, the majority of patients with diabetes were in
      the older age group (> or = 45 years) and many of them were overweight or obese.
      The majority of patients had lived in the city of Port Moresby for many years
      before their diagnosis. 74% of diabetic patients chewed betelnut before their
      diagnosis and had continued the habit while undergoing treatment for diabetes.
      The majority (80%) of patients had poor glycaemic control as indicated by the
      high mean of their most recent blood glucose, which was 13.0 mmol/l in male and
      13.1 mmol/l in female patients; these levels were not much lower than those at
      diagnosis. The mean follow-up of patients in the clinic was 6.2 years. On the
      balance of evidence, betelnut is a contributing factor to the poor glycaemic
      control in diabetic patients attending Port Moresby General Hospital.

PMID- 17212065
TI  - Barriers to measles immunization: the beliefs and attitudes of caregivers in
      Goroka, Eastern Highlands Province, Papua New Guinea.
AB  - In Papua New Guinea, measles remains a public health problem and the majority of
      measles cases occur in non-immunized children. In Goroka, measles vaccine
      coverage for the 9-month-old group was 44%. The parents or caregivers are
      important in measles prevention as children's immunization depends on their
      compliance. This study aimed to determine the factors that hinder caregivers from
      having their children vaccinated for measles prevention in the Goroka District,
      Eastern Highlands Province. A cross-sectional study was conducted in July-August
      2003, using pre-constructed questionnaires and interviews. There was a total of
      120 respondents who were caregivers or parents of children whose ages ranged from
      6 to 12 months and who attended health care centres where immunization services
      were provided. The main reasons for not bringing their children to clinic for
      immunization were: limited access to health centres, especially to maternal and
      child health (MCH) clinics; too long a waiting time at the clinic; concern that
      too many injections were being given to their children; the side-effects of the
      vaccine; being sent away and asked to come back the next day for immunization;
      and a bad reception from health workers. Funerals or election-related events in
      the area also affected the attendance at the clinic. In order to improve the
      vaccine coverage, the use of a mobile MCH clinic should be re-established. Health
      workers should utilize the opportunities to pass on necessary information on
      immunization to caregivers, as well as being mindful to use communication that
      will prevent misunderstanding by the mothers. It is important for all health
      workers to recognize that their performance and attitude can greatly improve the
      overall vaccine coverage in Papua New Guinea.

PMID- 17212066
TI  - Health care and illness in Lihir, New Ireland Province, in the context of the
      development of the Lihir gold mine.
AB  - During 2000 a review of health care and illness in Lihir, New Ireland Province,
      was carried out while I was employed as a Community Health Research Officer with
      the Lihir Management Company, the manager of a gold mine on Lihir. The review aim
      was to document the health care providers for the local population and the
      illness burden suffered by Lihirians, and then to shape services to have a more
      preventive emphasis. It was discovered that the health care services available
      were well utilized by Lihirians. Health care was provided by the church,
      government and the mining company, and needed better coordination of services.
      Lihirians faced a relatively heavy burden of illness, with malaria the most
      common affliction. They also suffered significantly from lymphatic filariasis and
      tuberculosis, and children were poorly nourished. A considerable number of
      recommendations have been adopted since the health review to improve the health
      of, and delivery of health services to Lihirians.

PMID- 17212067
TI  - Respiratory health effects associated with exposure to indoor wood burning in
      developing countries: a Papua New Guinea perspective.
AB  - Some of the highest exposures to air pollutants in developing countries occur
      inside homes where solid biofuel, particularly wood fuel, is used for daily
      cooking. A relatively high proportion of the world population living in these
      countries is exposed to increased levels of indoor air pollutants produced by
      inefficiently burning stoves. Inhalation of these pollutants may have serious
      consequences, which are highlighted in this paper, for the respiratory health of
      the people who have been exposed.

PMID- 17212068
TI  - Corticofugal modulation of sensory information.
AB  - Sensory signals reach the cerebral cortex after having made synapses in different
      relay stations along the sensory pathway. The flow of sensory information in
      subcortical relay stations is controlled by the action of precise topographic
      connections from the neocortex. Several lines of research indicate that the
      massive corticifugal system improves ongoing subcortical sensory processing and
      reorganizes the receptive fields in visual, auditory and somatosensory systems.
      In all these sensory systems cortical neurons mediate both the highly focused
      positive feedback to subcortical neurons with overlapping receptive fields and a
      widespread inhibition to "non-matching neurons". This cortical feedback, which
      has been called "egocentric selection", can play a pivotal role in gating the
      sensory information that reaches the thalamus and cortex. Thus, corticofugal
      projections may contribute to selective attention since they enhance neuronal
      responses for attentionally relevant stimuli and by suppressing sensory responses
      of distractive stimuli. Also, corticofugal projections enhance oscillatory
      activity in order to synchronize neurons located in the same or in different
      relay stations in order to improve sensory processing. In conclusion,
      corticofugal pathways precisely control sensory transmission through out the
      central nervous system.

PMID- 17212069
TI  - Left-right asymmetry in vertebrate development.
AB  - Externally the vertebrate body plan presents a bilateral symmetry in relation to
      the midline. However, inside the body the distribution of the visceral organs
      follows a very particular pattern that is not symmetrical in relation to the
      midline. The last 10 years have seen remarkable advances in our understanding of
      how the internal asymmetries typical of the vertebrate body are established and
      controlled. The use of different development models has permitted to uncover
      fascinating ways of creating asymmetry, like the activity of the nodal cilia. A
      host of studies has also unravelled the involvement of many genes in the left
      right patterning pathway. Based on this knowledge the genetic basis of human
      laterality defects are beginning to be revealed. It is a major challenge now to
      understand how all these genes control left right development as well as the
      complex set of interactions established between them.

PMID- 17212070
TI  - Genetic control of neuronal migrations in human cortical development.
AB  - The early steps in corticogenesis are decisive for the correct unfolding of
      neurogenesis, neuronal migration and differentiation under tight genetic control.
      In this monograph, we outline the main events in human preplate formation, the
      gradual transformation of the preplate into the cortical plate, and the
      establishment of the transient compartments of the foetal cortical wall. The main
      neuronal populations of the embryonic and fetal cortex are presented according to
      their timetable of appearance and the expression of developmentally relevant gene
      products, with the main focus on members of the Reelin-Dab1 signalling pathway,
      LIS1 and Doublecortin, all of which are crucial for cortical migration. The often
      significant developmental differences between the lissencephalic rodent brain,
      which has become the prevailing model of corticogenesis, and the highly
      differentiated, gyrated human brain are pointed out and discussed.

PMID- 17212071
TI  - Erosive tooth wear: diagnosis, risk factors and prevention.
AB  - PURPOSE: To provide an overview on diagnosis, risk factors and prevention of
      erosive tooth wear, which is becoming an increasingly important factor when
      considering the long- term health of the dentition. RESULTS: Awareness of dental
      erosion by the public is still not widespread due to the cryptic nature of this
      slowly progressing condition. Smooth silky-glazed appearance with the absence of
      perikymata and intact enamel along the gingival margin, with cupping and grooving
      on occlusal surfaces are some typical signs of enamel erosion. In later stages,
      it is sometimes difficult to distinguish between the influences of erosion,
      attrition or abrasion during a clinical examination. Biological, behavioral and
      chemical factors all come into play, which over time, may either wear away the
      tooth surface, or potentially protect it. In order to assess the risk factors,
      patient should record their dietary intake for a distinct period of time. Based
      on these analyses, an individually tailored preventive program may be suggested
      to patients. It may comprise dietary advice, optimization of fluoride regimes,
      stimulation of salivary flow rate, use of buffering medicaments and particular
      motivation for non-destructive tooth brushing habits. The frequent use of
      fluoride gel and fluoride mouthrinse in addition to fluoride toothpaste offers
      the opportunity to minimize abrasion of tooth substance.

PMID- 17212072
TI  - Fracture behavior of structurally compromised non-vital maxillary premolars
      restored using experimental fiber reinforced composite crowns.
AB  - PURPOSE: To study the fracture behavior of direct resin composite crowns with or
      without experimental fiber reinforcement. METHODS: Clinical crowns of single
      rooted maxillary premolars were cut off at the cemento-enamel junction. Canals
      were prepared with Gates Glidden drills up to size 4. No additional post-space
      preparations were made. Roots were embedded in acrylic and canal entrances were
      standardized (depth 2 mm, diameter 1.75 mm). Three groups of 14 samples were
      treated as follows: (1) custom-made glass FRC post (EverStick Post); fibers 5 mm
      deep in the canal, (2) similar post-system as (1) with incorporation of a new
      type of glass fiber fabric, (3) no fiber reinforcement (control). Posts were
      cemented with resin cement (Panavia F). Resin composite crowns (Filtek Z250) were
      made using an anatomically formed mold. Static load until fracture was applied
      using a universal loading device with a cylindrical bar (diameter 2 mm) with a
      crosshead speed of 5 mm/minute (loading angle: 30 degrees to the tooth long
      axis). Failure modes were categorized as favorable and unfavorable failures.
      RESULTS: There was no significant difference in mean failure loads among the four
      groups (P > 0.05). Favorable failures occurred significantly more often in Group
      2 than in the other groups (P < 0.05). The results suggest that an incorporated
      glass fiber fabric does not affect the load-bearing capacity of resin composite
      complete crowns on structurally compromised and non-vital premolars.
      Incorporation of a glass fiber fabric, however, has a beneficial effect on the
      failure mode.

PMID- 17212073
TI  - Effect of the seating pressure on the adhesive bonding of indirect restorations.
AB  - PURPOSE: To evaluate the effect of two different techniques of seating pressure
      application on the adhesive-dentin bond of indirect restorations. METHODS: Eight
      non-carious human third molars were randomly divided in two treatment groups
      (four teeth each). Cylindrical composite blocks were luted with a resin cement
      (Panavia F). In Group 1, the seating pressure was applied for 5 seconds. In Group
      2, the resin cylinder was maintained under constant pressure during the entire 3
      minute polymerization period of the resin cement. After storing in distilled
      water for 24 hours, 0.9 x 0.9 mm sticks were produced from these luted specimens
      for microtensile bond testing and SEM examination. RESULTS: The Student t-test
      showed a significant difference (P < 0.05) in bond strength between Groups 1 and
      2. SEM revealed the presence of structural defects and resin globules on the
      seating surface of the composites. These features were exclusively identified
      from Group 1 specimens and were probably caused by fluid transudation from the
      underlying dentin through the simplified self-etch adhesive (ED primer).

PMID- 17212074
TI  - Marginal quality in enamel and dentin after preparation and finishing with an
      Er:YAG laser.
AB  - PURPOSE: To find the most appropriate Er:YAG laser parameters for an optimal
      marginal adaptation of Class V restorations in enamel and dentin. METHODS: Six
      saucer-shaped mixed Class V cavities were prepared in each of the eight
      experimental groups with an Erbium:YAG hard laser (Opus Duo) on extracted human
      molars in near contact mode with a conical 800 microm sapphire tip under
      continuous water spray by using different pulse energy and pps (pulse per second)
      parameters. The cavities were restored under the simulation of dentin fluid with
      Clearfil SE Bond and Clearfil APX PLT composite applied in two layers and light
      cured. Marginal adaptation in enamel and dentin was quantified before and after
      simultaneous thermal (5-50-5 degrees C, 2 minutes each) and mechanical (max. 49N;
      1,200,000 cycles) stresses by using the replica technique in a SEM under x200
      magnification. RESULTS: With the exception of dentin margins before loading,
      significant differences for percentages of "continuous margin" and "enamel
      fractures" were detected before and after loading (P < 0.05, ANOVA, Student's t
      test). A pulse energy of 100 mJ both on dentin and enamel was found optimal for
      finishing and smoothing the preparation margins after cavity preparation with 500
      mJ or more.

PMID- 17212075
TI  - Stain retention and surface characteristics of posterior composites polished by
      one-step systems.
AB  - PURPOSE: To compare susceptibility to stain of three posterior composite surfaces
      polished with two one-step polishing systems, to test the efficiency of the re
      polishing to remove the stain formed and to analyze the polished surfaces by SEM.
      METHODS: The resin composites tested were Clearfil Photo Posterior, SureFil and
      Filtek P60. The polishing systems used were Sof-Lex Brush and PoGo. Twenty-two
      discs of each material were fabricated and divided into two treatment groups of
      11. Out of the latter, six were used for SEM evaluation for surface morphology
      and five for stain retention testing. The discs were roughened with silicon paper
      and polished for 30 seconds with each system. Specimens were immersed in coffee
      and distilled water for 7 days. Color measurements were made at baseline and
      after 1, 3, 5, and 7 days with a spectrophotometer. The specimens were then re
      polished with the same systems and their colors re-measured. All comparison of
      color change and re-polishing were subjected to repeated measures ANOVA with a
      Bonferroni post hoc test (P < or = 0.05). RESULTS: After 1 week, the coffee
      stained all the resin composites. Clearfil Photo Posterior was the least stained
      composite while Filtek P60 was the most. Regardless of the materials, PoGo
      polishing was less susceptible to staining (P < or = 0.05). The color change
      could be partially removed with re-polishing. The surfaces of Sof-Lex Brush
      polished samples, except the Clearfil group, were scratched and thus more
      susceptible to stain retention.

PMID- 17212076
TI  - Effect of antioxidant on coronal seal of dentin following sodium-hypochlorite and
      hydrogen-peroxide irrigation.
AB  - PURPOSE: To reduce the microleakage of a self-etching priming dentin adhesive
      with the use of antioxidant or bur finishing after sodium-hypochlorite or
      hydrogen-peroxide irrigation. METHODS: 70 single-root canals were enlarged and
      seven different treatment protocols were applied throughout the root canal
      treatment: The roots in Groups 1, 2, and 3 were irrigated with sodium
      hypochlorite. Group 1 was used as the negative control with only sodium
      hypochlorite irrigation whereas in Group 2, sodium-ascorbate was applied as an
      additional irrigation agent following sodium-hypochlorite. Irrigation procedure
      in Group 3 was same as in Group 1, however, after the roots in this group were
      obturated, cavities were cleaned off with a carbide bur (bur-finishing) to remove
      the effect of sodium-hypochlorite. Hydrogen-peroxide irrigation was used in
      Groups 4, 5 and 6; the procedural steps were similar to those of Groups 1, 2 and
      3: hydrogen-peroxide in Group 4, sodium-ascorbate application in Group 5, and bur
      finishing in Group 6. Group 7 was the positive control with saline irrigation
      alone. All roots were obturated with Diaket sealer and gutta-percha cones using
      cold lateral condensation technique immediately after irrigation. A self-etching
      priming adhesive plus resin composite was applied after the endodontic treatment.
      The microleakage of dentin margins was determined using dye-penetration technique
      with clearing process. RESULTS: The Kruskal-Wallis followed by Mann-Whitney test
      showed that both sodium-hypochlorite and hydrogen-peroxide deteriorated the
      marginal seal of the dentin adhesive (P < 0.05), however, following both
      irrigation solutions the use of sodium-ascorbate reduced the microleakage (P <
      0.05). Additionally, when sodium-ascorbate or bur-finishing was applied to remove
      the deterioration caused by sodium-hypochlorite or hydrogen-peroxide, the
      microleakage scores obtained were not different from that of the positive control
      (P > 0.05).

PMID- 17212078
TI  - Survival of self-etch adhesive Class II composite restorations using ART and
      conventional cavity preparations in primary molars.
AB  - PURPOSE: To test the null-hypothesis that there was no difference in the survival
      percentages of Class II composite restorations in primary teeth produced through
      either ART or conventional approaches after 2 years. METHODS: 157 children with
      325 Class II cavitated dentin lesions were included in a split-mouth study
      design. A computer program randomly assigned cavitated dentin lesions to
      treatment groups stratified for gender, operator, upper/lower jaw and left/right
      side of the mouth. Three operators placed resin composite (Pertac II)
      restorations using a self-etch adhesive (Prompt L-Pop). Two independent examiners
      evaluated the restorations after 0.5, 1 and 2 years using the modified Ryge
      criteria. A modification of the actuarial survival method was applied to estimate
      survival percentages. RESULTS: There was no statistically significant difference
      (P > 0.05) observed between the cumulative survival percentages of Class II
      composite restorations in primary teeth produced by the two approaches after 2
      years (ART: 34.9% +/- 4.7%; conventional: 35.1% +/- 4.7%). The cumulative
      survival percentages of ART and conventional Class II restorations of one of the
      operators were lower than for ART restorations of the other two operators and for
      conventional restorations of one of the operators (P < or = 0.001). The main
      reason for Class II composite restorations to fail over the 2-year period was
      complete loss of retention; ART: 75%; conventional: 77%. The null-hypothesis was
      accepted as there was no difference in the cumulative survival percentages of ART
      and conventional Class II composite restorations in primary teeth after 2 years.
      It appears that the low survival results obtained may have been caused by poor
      bonding of the self-etch adhesive.

PMID- 17212077
TI  - Cleaning effectiveness and shaping ability of rotary ProTaper compared with
      rotary GT and manual K-Flexofile.
AB  - PURPOSE: To compare the cleaning efficacy and shaping ability of engine-driven
      ProTaper and GT files, and manual preparation using K-Flexofile instruments in
      curved root canals of extracted human teeth. METHODS: 45 canals of maxillary and
      mandibular molars with curvatures between 25 degrees and 40 degrees were divided
      into three groups. The groups were balanced with regard to the angle and the
      radius of canal curvature. Canals in each group were prepared to an apical size
      of 25 with either the rotary ProTaper or GT system, or manually with K-Flexofile
      using the modified double-flared technique. Irrigation was done with 2 mL 2.5%
      NaOCl after each instrument and, as the final rinse, 10 mL 2.5% NaOCl then 10 mL
      17% EDTA and finally 5 mL distilled water. The double-exposure radiographic
      technique was used to examine for the presence of apical transportation. The time
      required to complete the preparation, as well as any change in working length
      after preparation were recorded. The roots were then grooved and split
      longitudinally. The amounts of debris and smear layer were evaluated at the
      apical, middle and coronal regions under the scanning electron microscope. Data
      were analyzed either parametrically with the F-test or non-parametrically using
      the Kruskal-Wallis test, where appropriate. RESULTS: Two GT files but none of the
      K-Flexofile and ProTaper instruments separated. For debris removal, the ProTaper
      group achieved a better result than GT (P < 0.05) but not the K-Flexofile group
      at all three regions (apical, middle and coronal). K-Flexofiles produced
      significantly less smear layer than ProTaper and GT files only in the middle
      third of the canal (P < 0.01). Both NiTi rotary instruments maintained the
      original canal shape better than the K-Flexofiles (P < 0.05) and required
      significantly less time to complete the preparation.

PMID- 17212079
TI  - In vitro wear evaluation of dental materials in primary teeth.
AB  - PURPOSE: To evaluate the effect of dental materials on primary enamel wear.
      METHODS: Four composites (Filtek Z250, Heliomolar, Point 4, SureFil), two
      compomers (Dyract AP, F2000) and a resin-modified glass-ionomer (Vitremer) were
      placed into box-shaped preparations in buccal surfaces of primary molars and
      stored for 24 hours in water at 37 degrees C. The specimens (n = 6) were
      subjected to abrasive three-body wear against a primary enamel cusp. Material
      wear, enamel wear (adjacent to the material), and wear on enamel cusps were
      estimated by profilometry and video-analysis software. Results were compared with
      ANOVA and Tukey's tests (P < 0.05). RESULTS: Vitremer showed the highest wear (P
      < 0.05), followed by Dyract AP and F2000, which were not statistically different
      (P > 0.05). There was no significant difference between Filtek Z250 and Dyract AP
      (P > 0.05). Filtek Z250, Heliomolar, Point 4 and SureFil, showed the lowest wear
      values and there was no difference among them (P > 0.05). The highest wear values
      on the enamel adjacent to the material were found with Dyract AP (P < 0.05) and
      the lowest next to Point 4 and SureFil (P < 0.05). There was no difference in the
      wear of the enamel next to Vitremer, F2000, Heliomolar and Filtek Z250 (P >
      0.05). Vitremer and F2000 caused the highest wear on enamel cusps (P < 0.05), and
      there was no statistically significant difference (P > 0.05) between them;
      SureFil caused the lowest wear (P < 0.05) on the opposing enamel. There was a
      correlation (r = 0.85) between wear of materials and wear on the enamel cusps,
      but not (r = 0.53) for the wear on enamel besides the restoration and wear on
      enamel cusps. SEM micrographs showed different surface characteristics of the
      materials after the wear test.

PMID- 17212080
TI  - Migration and particle clearance from hard-setting Ca(OH)2 and self-etching
      adhesive resin following direct pulp capping.
AB  - PURPOSE: To evaluate the migration and particle clearance from a hard-setting
      calcium hydroxide (HSCH) and self-etching adhesive resin (SEAD) following direct
      pulp capping using the light and electron microscope. METHODS: Exposed monkey
      pulps were capped with a hard-setting calcium hydroxide (Dycal) or adhesive resin
      (Clearfil SE Bond), and histopathologically evaluated at 14 and 21 days using
      light and transmission electron microscopy (n = 14). RESULTS: At 14 days, both
      HSCH and SEAD materials showed no severe inflammatory reactions of the pulp
      (necrosis and abscess formation). The main reaction was slight inflammatory cell
      infiltration consisting of leukocytes. A number of HSCH particles were entrapped
      by macrophages and observed in the small capillaries similar to blood or
      lymphatic vessels. For SEAD, slight hemorrhage was observed at the exposed
      surface. At 21 days, for both HSCH and SEAD, a few cases showed minimal
      inflammatory response which was limited to the area beneath the exposure. Some
      macrophages entrapping the HSCH particles in vacuoles within the cytoplasm were
      arranged at the surface of the capping layer. HSCH particles were also observed
      in the vessels similar to blood or lymphatic vessels. A few macrophages entrapped
      filler-like particles of SEAD adjacent to the capping material, but there was no
      evidence of any SEAD in the vessels.

PMID- 17212081
TI  - Clinical evaluation of a polyacid-modified resin composite (Dyract AP) in Class I
      cavities: 3-year results.
AB  - PURPOSE: This study evaluated the 3-year clinical performance of the polyacid
      modified resin composite Dyract AP in restorations for Class I carious lesions.
      METHODS: 108 Class I cavities in 21 subjects were restored with Dyract AP. The
      lesions, which were diagnosed macroscopically with a probe, involved fissures and
      had reached the dentin, while lateral spread was limited and localized to the
      dentin. The average facio-lingual width of the cavities was equal to or less than
      one-third the intercuspal width. Restorations were evaluated clinically by two
      experienced, calibrated examiners at baseline and at 1, 2, and 3 years, according
      to the modified Ryge criteria, (color match, marginal discoloration, wear or loss
      of anatomical form, caries, marginal adaptation, and surface texture). RESULTS:
      None of the restorations failed at the end of the first year. At 2 years, two
      restorations required immediate replacement due to caries lesions adjacent to the
      margins. At 3 years, six restorations had caries lesions adjacent to their
      margins, and the cumulative rate of success was 93.4%. Color changes and marginal
      discolorations were found to be statistically significant (P < 0.001) at 3 years,
      although none of the restorations needed to be replaced. Significant differences
      were also observed in the caries rate (P < 0.001) at 3 years. Aside from the
      eight failed restorations, the degrees of color matching, marginal discoloration,
      wear or loss of anatomical form, caries, marginal adaptation, and surface texture
      were clinically acceptable at 3 years post-treatment.

PMID- 17212082
TI  - Clinical and microbiological effect of calcium hydroxide protection in indirect
      pulp capping in primary teeth.
AB  - PURPOSE: To evaluate clinically and microbiologically the effect of calcium
      hydroxide (CH) on carious dentin on primary teeth submitted to indirect pulp
      capping (IPC). METHODS: Twenty 4-7 year-old subjects with 42 treated teeth
      participated in the study. The treatment consisted of incomplete excavation of
      the demineralized dentin, application of a CH or gutta-percha (GP) layer and
      sealing with a resin-based composite for 4-7 months. After cavity preparation and
      sealing, the dentin was evaluated clinically (color and consistency) and
      microbiologically. Dentin samples were cultured on blood agar under aerobic and
      anaerobic conditions, in Mitis Salivarius agar and Rogosa SL agar. RESULTS: 39
      teeth (20 in the CH Group and 19 in the GP Group) were reopened 4-7 months post
      treatment for clinical and microbiological evaluation. In all teeth, the initial
      demineralized dentin was wet and soft or leathery. In the CH Group, 10% of the
      lesions were yellow, 80% light brown and 10% dark brown and in the GP Group,
      94.7% were light brown and 5.3% dark brown. After treatment, the dentin was dry,
      90% (Group CH) and 84.2% (Group GP) were dark brown. The final consistency was
      either leathery or hard. Three samples in the CH Group and five in Group GP
      changed from soft to leathery; only one sample (GP) remained leathery. 85% in the
      CH Group and 68.4% in GP Group turned hard after treatment. All bacterial counts
      decreased significantly by the end of treatment. In the CH Group, the bacterial
      (Log10 CFU + 1) anaerobic growth decreased from 4.84 +/- 1.31 to 1.35 +/- 1.54,
      aerobic from 4.09 +/- 1.04 to 0.92 +/- 1.30 and lactobacilli from 3.24 +/- 1.22
      to 0.36 +/- 0.89, respectively; the mutans streptococci from 2.05 +/- 1.84 to
      0.14 +/- 0.60. In GP Group, anaerobic growth decreased from 5.22 +/- 0.96 to 2.02
      +/- 1.65 and aerobic from 4.23 +/- 1.37 to 1.08 +/- 1.29 and lactobacilli from
      2.06 +/- 1.81 to 0.00 +/- 0.00, respectively; the mutans streptococci from 3.16
      +/- 1.59 to 0.28 +/- 0.84.

PMID- 17212083
TI  - Effect of tooth-bleaching on the tensile strength and staining by caries detector
      solution on bovine enamel and dentin.
AB  - PURPOSE: To evaluate the tensile strength and staining of enamel and dentin after
      extracoronal or intracoronal bleaching using conventional bleaching agents.
      METHODS: Extracted bovine incisors were divided into eight groups of 10
      specimens. Individual groups were treated by extracoronal bleaching (E) using in
      office and home techniques with different concentrations of hydrogen peroxide
      (H2O2) and carbamide peroxide (CP); no bleaching (EN), 35% H2O2 and 10% CP (E35H
      10C), 35% H2O2 and 20% CP (E35H-20C), 35% CP and 10% CP (E35C-10C), 35% CP and
      20% CP (E35C-20C). Intracoronal "walking bleaching" (I) was performed after 24
      hours of root canal treatment in the three remaining groups; no bleaching (IN);
      sodium perborate dissolved in 35% H2O2 (ISP-35H); and sodium perborate in
      distilled water (ISP-W). Mini dumbbell shapes of enamel and dentin with central
      cross-section diameters of 1.5 x 0.5 mm and 3 x 1 mm respectively were prepared
      for tensile testing using an Instron machine. Fracture surfaces were examined
      using SEM. Bleached enamel and dentin specimens were stained and evaluated using
      Caries Detector solution. Staining scores were analyzed using Kruskal-Wallis H
      and Mann-Whitney test (P < 0.05). RESULTS: Tensile strengths (mean +/- SD) of
      enamel and dentin respectively for each group in MPa were: EN = 30.5 +/- 3.3 and
      85.4 +/- 3.0, E35H-10C = 14.8 +/- 2.3 and 58.9 +/- 2.0, E35H-20C = 10.6 +/- 2.6
      and 55.5 +/- 2.2, E35C-10C = 25.4 +/- 3.4 and 70.8 +/- 2.5, E35C-20C = 20.3 +/-
      4.1 and 67.2 +/- 3.3, IN = 26.5 +/- 4.1 and 85.9 +/- 2.5, ISP-35H = 13.6 +/- 3.1
      and 46.7 +/- 2.3, ISP-W = 21.7 +/- 3.3 and 68.3 +/- 4.4. ANOVA and Tukey HSD test
      found statistically significant differences among and between groups respectively
      (P < 0.05). No significant difference was found between non-bleached groups (IN
      and EN) of enamel and dentin. Mean tensile strengths of all bleached groups were
      significantly lower than those of non-bleached groups. Fracture surfaces
      demonstrated the different morphologies for bleached and non-bleached enamel and
      dentin.

PMID- 17212084
TI  - [Tissue array analysis of the aberrant expression of HLA class I molecules in
      human non small cell lung cancer].
AB  - A clinical significance of the aberrant expression of HLA class I molecules
      including HLA class I and HLA-G was analyzed using tissue array analysis. Our
      institute has established a two millimeter spot sized tissue array set of 105
      clinical cases of resected human non small cell lung cancer tissues. A loss of
      HLA class I was observed in the 58.3% of cancer tissues. The aberrant expression
      of HLA G was also observed in the 55.2% of cancer tissues. Statistically
      significant correlations were observed among HLA class I expression and tumor
      size, nodal involvement and pathological stage. Survival analyses were shown that
      the HLA class I loss was correlated to a recurrence free survival time. The HLA-G
      expression did not correlate with any clinico-pathological parameters. A loss of
      HLA class I was probably involved due to a cancer progression in human non-small
      cell lung cancer through the mechanism of immune escape from the host immune
      system.

PMID- 17212085
TI  - [Plasma methylation-specific polymerase chain reaction as a diagnostic tool for
      esophageal cancer patients].
AB  - This study was designed to perform methylation-specific polymerase chain reaction
      (MS-PCR) assay for p16, E-cadherin, and retinoic acid receptor beta genes on
      peripheral blood samples from patients with esophageal squamous cell cancers, and
      compare the results of MS PCR with conventional serum tumor markers and the CEA
      specific reverse transcriptase polymerase chain reaction (RT-PCR) assay.
      Preoperative blood samples were obtained from 30 patients with esophageal cancer,
      and were subjected to MS PCR and RT-PCR assays. Eleven patients (37%) showed
      aberrant methylation of the promoter region of at least one gene. On the other
      hand, circulating tumor cells were detected in 11 patients (37%). There was no
      correlation between both results and conventional tumor markers. The MS-PCR and
      RT-PCR assays can serve as complementary diagnostic markers for screening and
      monitoring patients with esophageal cancers.

PMID- 17212086
TI  - [An early detection of recurrence using reverse transcriptase-polymerase chain
      reaction (RT-PCR) and methylation-specific polymerase chain reaction (MSP) from
      peripheral blood in patients after gastrectomy].
AB  - Several molecular approaches, using peripheral blood of patients with cancers,
      have been assessed recently for ability to detect various primary and recurrent
      cancers at an early stage. One is the reverse transcriptase polymerase chain
      reaction (RT-PCR) analysis, which can detect a small number of circulating cancer
      cells. Another is the methylation-specific polymerase chain reaction (MSP), which
      detects tumor-specific alterations of cell-free serum DNA released from tumor
      into the circulation by necrosis and/or apoptosis. In the present study, we set
      out to assess the diagnostic value of the RT-PCR assay and the MSP assay for an
      early detection of recurrent diseases in patients after curative gastrectomy. Two
      of the 25 patients (8%) exhibited a CEA specific signal in their peripheral
      blood. On the other hand, seven patients (28%) showed aberrant methylation of the
      promoter region of at least one gene (3 patients for p16, 3 for E-cadherin, 3 for
      RARbeta genes, and 1 for CDH4 respectively). No abnormal signal was detected in
      sera from volunteers who served as controls. Of 10 patients who developed
      recurrences, a CEA-specific signal and aberrant methylation was demonstrated in
      plasma samples of 1 and 4 patients, respectively. One patient, without definite
      findings of recurrence at the time of analysis, developed recurrences 6 months
      later. Both assays can serve as markers that allow selection of those cases
      requiring more intensive screening and aggressive postoperative treatment.

PMID- 17212087
TI  - [The relationship between gene expression of Bcl-2 and Bax and the therapeutic
      effect in oral cancer patients].
AB  - We have investigated the relationship between gene expression of Bcl 2 and Bax
      and the therapeutic effect in oral cancer patients. A significant correlation
      between Bcl-2/Bax gene expression ratio in the peripheral blood mononuclear cells
      (PBMCs) from the patients, and the therapeutic effect of radiation therapy in
      combination with UFT and OK-432, as well as survival rate, was observed. In
      addition, the statistically significant correlation was also observed between Bcl
      2/Bax ratio and IFN-gamma and NK activity induced with OK-432. These findings
      suggest that Bcl-2 and Bax gene expression in PBMCs may be useful as a prognostic
      factor in oral cancer patients.

PMID- 17212088
TI  - [Anti tumor activities of lentinan and micellapist in tumor-bearing mice].
AB  - Although Lentinan (LNT) is sold as a medicine, and Micellapist (MME) sold as a
      food supplement, both LNT and MME are beta-glucans isolated from the Shiitake
      mushroom (Lentinula edodes). These two substances have been thought to be the
      same component of Shiitake. In the present study, we evaluated anti tumor
      activities of LNT and MME in tumor-bearing mice (B10.D2 mice implanted with
      S908D2 tumor cells) and examined the mechanism of immunopotentiation of these
      substances. The tumor growth was significantly suppressed in the LNT-treated
      group. In ex vivo evaluation, the tumor cytotoxicity was significantly reduced by
      a treatment of splenocytes with anti-CD8 antibody in the LNT-treated group.
      Furthermore, the tumor cytotoxicity of the LNT-treated group was also
      significantly reduced by a treatment of splenocytes with anti-CD8 antibody and
      its complement and with an anti-CD4 and its complement in the effector phase and
      the induction phase, respectively. A significant prolongation of the survival of
      tumor-bearing mice as compared to the untreated control group was noted in the
      LNT-treated group. In the mice treated intraperitoneally with LNT, CD8-positive
      cells appeared to have suppressed tumor cell proliferation. CD4-positive cells
      appeared to be involved in this activity of CD8-positive cells. On the other
      hand, orally administered MME has exerted no clear cytotoxic effects.

PMID- 17212089
TI  - [Can the survival of patients with recurrent disease after curative resection of
      colorectal cancer be prolonged by the administration of cimetidine?].
AB  - Administration of cimetidine after curative surgery can improve prognosis of
      patients with colorectal cancer. In this study, we analyzed whether cimetidine
      can influence the survival of patients with a recurrent disease after colorectal
      surgery. The subjects were 29 patients with recurrent disease: 14 patients were
      administered with cimetidine and 15 patients were not. In the cimetidine
      administered group, seven cases were recurrent in the liver, 5 cases in a local
      site and 1 case in the lymph node, whereas 7 cases were recurrent in the liver, 4
      cases in a local site and 3 cases in the lung for the non-cimetidine administered
      group. There were no significant differences for both groups in terms of
      patient's survival after recurrence. Although it was not significant, the
      patient's survival after curative resection of recurrent disease for the
      cimetidine administered group was better than the non cimetidine administered
      group. Although the results did not show cimetidine could influence the overall
      survival of the patients after recurrence, it might be possible to improve the
      survival of the patients after resection of the recurrent disease.

PMID- 17212090
TI  - [A case of immunotherapy using OK-432 in combination with RFA for CRT-resistant
      recurrent tumors of esophageal cancer that presented itself in the
      intramediastinal omentum of gastric tube].
AB  - The greater omentum contains abundant lymphoid tissues composed of a lot of
      macrophages and lymphocytes, and plays an important role in a host defense system
      in the peritoneal cavity. Also, it is well known to be an initial site of
      peritoneal disseminated metastases. We experienced a rare case of a 60-year-old
      man with postoperative recurrence of esophageal cancer that presented itself in
      the greater omentum of the gastric tube reconstructed through a mediastinal
      route, as well as through mediastinal lymph-nodes. We performed CT-guided
      radiofrequency ablation (RFA) for recurrent omental tumor that was refractory to
      chemoradiation therapy and growing rapidly adjacent to the trachea. In
      combination with local control using RFA, we attempted a systemic immunotherapy
      using OK-432, by subcutaneous injection around RFA to accelerate host antitumor
      immune responses induced by antigen stimulation by RFA, based on the
      immunological property of the omentum. RFA induced a significant therapeutic
      effect on the omental tumor with massive necrotic change. However, no apparent
      size reduction was seen in the metastatic mediastinal lymph nodes, although an
      increase of peripheral blood lymphocytes was observed before and after RFA, and
      systemic host immune responses were stimulated by OK-432.

PMID- 17212091
TI  - [A possibility of overcoming local tumor immune tolerance by radiofrequency
      ablation in combination with intratumoral injection of naive dendritic cell].
AB  - Recently we reported the systemic antitumor efficacy of intratumoral naive
      dendritic cell injection (IT-DC) in combination with local photodynamic therapy
      in Clinical Cancer Research 2006. In general, tumor cells secrete several immune
      suppression cytokines which could induce immune tolerance in a tumor
      microenvironment. The rationale and advantages of IT DC in combination with
      conventional antitumor therapy are as follows: (1) dying tumor cells release some
      tumor antigens, (2) sufficient number of DC recruiting occurs at tumor site, (3)
      there is naive DC capturing some tumor antigens in vivo, (4) DC activation by
      inflammatory cytokines are released from dying tumor cells, and (5) DC migration
      happens in regional lymph nodes and induces adoptive tumor immunity. Conventional
      antitumor therapy before IT DC could destroy the immune tolerance at a tumor site
      and induce durable DC vaccination. In this report, we demonstrated the mechanism
      of (4) and (5) by radiofrequency ablation plus IT DC using mouse tumor model.

PMID- 17212092
TI  - [Successful immunotherapy combined with hyperthermia therapy for cancer
      patients].
AB  - We proceeded with activated lymphocytes immunotherapy for 149 cancer patients,
      and hyperthermia therapy for 126 patients, and DC therapy for 20 patients in the
      past year. We were successful in two cases. Case 1: A metastatic pelvic cancer
      (unknown origin) patient treated with lymphocytes and hyperthermia therapy. She
      showed a drastic response. Case 2: A metastatic lymph node cancer patient treated
      with DC, lymphocytes and hyperthermia therapy. She showed a CR.

PMID- 17212093
TI  - [Possibilities of glypican-3-specific immunotherapy for hepatocellular
      carcinoma].
AB  - The patients with hepatitis B or C based liver cirrhosis are at high risk for
      developing Hepatocellular carcinoma (HCC), and HCC patients treated surgically or
      by other therapies are also at high risk for recurrence. As a result, the
      prognosis of HCC remains poor, and new therapies for the prevention of cancer
      development and recurrence are urgently needed. We previously reported that
      glypican 3 (GPC3) was over expressed specifically in HCC. In this report, we
      found the HLA-A2 or HLA-A24 restricted GPC3 epitope peptide, and investigated
      whether these peptides could induce GPC3 reactive CTLs from the peripheral blood
      mononuclear cells (PBMCs) of HLA-A2+ or HLA-A24+ HCC patients. We used HLA-A2.1
      (HHD) transgenic mice (Tgm) to identify the HLA-A2-restricted GPC3 epitopes. We
      found that these epitope peptides could induce peptide-reactive CTLs in about 50%
      of HLA A2+ or HLA-A24+, and GPC3+ HCC patients. Our study raises the possibility
      that these GPC3 peptides may therefore be applicable to cancer immunotherapy for
      prevention of cancer development and recurrence of HCC.

PMID- 17212094
TI  - [A phase I study of combination-therapy using personalized peptide vaccine and
      UFT/UZEL for advanced or recurrent colorectal cancer].
AB  - We herein administered combination-therapy using a personalized vaccination and
      the oral administration of UFT/UZEL for the treatment of either advanced or
      recurrent colorectal cancer. Safety and the efficacy of this new treatment
      modality were evaluated. Eight patients were enrolled in this clinical trial from
      July 2005 to May 2006. Up to 4 kinds of peptide vaccines which were selected
      according to the immune response of each patient were injected hypodermically
      every week. At the same time, UFT (300 mg/m2/day) and UZEL (75 mg/day) were also
      administered orally for 28 days followed by a 7-day rest period. Regarding the
      adverse events, callosity, a type of leukopenia, and liver-dysfunction, such as
      hyperbilirubinemia, an increase in the aminotransferase were observed. During the
      clinical evaluation after the end of the 2 courses, 3 cases showed progressive
      disease (PD) while 5 cases showed stable disease (SD). Our findings indicate that
      additional peptide vaccine therapy with UFT/UZEL, can be administered without
      compromising the patient's safety. Moreover, the use of UFT/UZEL does not
      normally interfere with the normal course of immune-therapy.

PMID- 17212095
TI  - [Acquired tumor "robustness" in the case of prostate cancer].
AB  - Tumors are highly robust and maintain their proliferative potential against both
      a wide range of host-defense mechanisms and anticancer therapies. In this study,
      we investigated the levels of human leukocyte antigen (HLA) class I, multi-drug
      resistance 1 (MDR1), and androgen receptor (AR) expressions in untreated prostate
      cancers harvested by radical prostectomy. The mean percentages of cancer cells
      expressing HLA class I, MDR1, and AR among the 10 cancer samples were 41, 35, and
      74%, respectively. In addition, double-staining of HLA class I and MDR1 revealed
      the four definite populations (HLA class I(+)/MDR(+), HLA class I(+)/MDR(-), HLA
      class I (-)/MDR(+), and HLA class I(-)/MDR(-)) in cancer tissues from the
      majority of cancer patients tested, and the mean percentages of cells expressing
      these combinations were 13, 29, 22, and 38%, respectively. Similar results were
      obtained by double staining of HLA class I and AR, except for 2 cases in which
      HLA class I(-)/AR (+) cancer cells predominated. These results indicated that
      untreated prostate cancer cells acquired a wide range of genomic mutation, which
      may have been caused by internal host pressure to eliminate malignant cells, and
      would provide evidence of the robustness of untreated prostate cancer.

PMID- 17212096
TI  - [Two cases of primary peritoneal cystadenocarcinoma--diagnosis, treatment, and
      clinical feature].
AB  - Primary peritoneal adenocarcinoma is rare, originating in the paramesonephric
      duct (mullerian duct). We report two cases of primary peritoneal adenocarcinoma.
      Both patients received a surgical resection. The pathological diagnosis of the
      resected specimen was papillary adenocarcinoma with clear cell carcinoma. The
      response after the combination chemotherapy using CDDP and TS-1 was "PR", and
      these treatments were effective to improve the patients' quality of life in each
      case.

PMID- 17212097
TI  - [An antitumor effect of oncolytic adenovirus capable of selectively replicating
      in CEA-expressing cancer cells and its enhancement by 5-FU].
AB  - In recent years, many have focused on the use of oncolytic virus capable of
      lysing cancer cells by a cancer-selective replication for a new treatment
      modality of cancer. In the present study, we used oncolytic adenovirus,
      AdCEAp/Rep, genetically modified to selectively replicate in CEA-expressing
      cancer cells, and investigated whether AdCEAp/Rep could induce selective
      cytotoxicity to CEA expressing cancer cells, and where the AdCEAp/Rep induced
      cytotoxic effect could be enhanced by 5 FU in using human gastric cancer cell
      lines, MKN45 (CEA-positive) and MKN74 (CEA-negative). The results showed that
      AdCEAp/Rep showed cytotoxicity against MKN45 in a dose-dependent manner, while it
      did not against MKN74. Furthermore, 5-FU remarkably enhanced AdCEAp/Rep-induced
      cytotoxicity against MKN45 by being added 3 days after adenovirus infection.
      These findings strongly suggest that AdCEAp/Rep may be applicable as a new
      therapeutic agent for clinical cancers expressing CEA in combination with
      chemotherapeutic agents such as 5-FU.

PMID- 17212098
TI  - [Prophylactic hepatic arterial infusion chemotherapy after curative surgery of
      colorectal liver metastases--the viewpoint from patients' quality of life].
AB  - In order to establish a reasonable prophylactic hepatic arterial infusion (HAI)
      chemotherapy following curative resection of colorectal liver metastases, the
      authors performed a randomized control study comparing two regimen. A weekly 5
      hour-administration of 5-FU (1500 mg) which was repeated for 8 weeks showed a
      comparable effect to a continuous infusion group with an identical total dosage
      of 5-FU. Furthermore, adverse events were observed in only several patients of
      each group with low grade severity, suggesting that this simple regimen with a
      weekly HAI is promising. We also analyzed the clinical course of patients
      receiving HAI using a W spiral catheter which has a shape memory alloy in its
      tip. The catheter was implanted angiographycally without coil fixation to the
      vascular wall, which allowed us to remove the catheter after cessation of the
      scheduled chemotherapy. In all of the patients, the catheters were easily removed
      without any complications. A 3D-CT angiograph revealed that the hepatic arteries
      were well patent in all of the patients with a 3.3 Fr type catheter. HAI
      chemotherapy is basically an invasive treatment. In consideration of its
      efficacies as well as limitations, a reasonable approach is needed from the
      viewpoint of patients' quality of life.

PMID- 17212099
TI  - [The efficacy of gastrojejunostomy for patients with unresectable gastric
      cancer].
AB  - We evaluated the efficacy of gastrojejunostomy for patients with unresectable
      gastric cancer. Thirteen patients had undergone gastrojejunostomy (GJ group) and
      14 patients who couldn't receive gastrojejunostomy, but had only been observed
      into their abdomen in the operation (S group). Between two groups, there were no
      significant differences in the effective rate, median survival time and the
      number of dates the patient stayed home after the operation. Gastrojejunostomy
      was useful for patients with a strong case of stenosis in the stomach, and may
      improve the quality of life as one of the multimodal therapy.

PMID- 17212100
TI  - [Augmented regional pancreatoduodenectomy ensures an excellent pain control for
      the case with pancreatic cancer invading the superior mesenteric artery and
      vein].
AB  - A 49-year-old woman with a complaint of severe abdominal pain and lumbargo was
      diagnosed with pancreatic cancer invading the superior mesenteric artery and
      vein. Since the lesion was unresectable by general Whipple's procedure, she was
      treated with gemcitabine and opiate. However, these treatments resulted in
      failure due to the side effects such as bone marrow suppression, severe nausea,
      and constipation. After the bone marrow suppression disappeared, she received
      augmented regional pancreatoduodenectomy, which is a pylorus preserving
      pancreatoduodenectomy with resection of the superior mesenteric artery and vein.
      Consequently, she could have a good QOL without opiates.

PMID- 17212101
TI  - [Laparoscopic adrenalectomy for the adrenal gland metastasis from hepatocellular
      carcinoma].
AB  - We present a case of a 70-year-old man with an anamnesis of intra-cerebral
      bleeding that resulted in right half of the body paralysis and right diaphragm
      paralysis, The present clinical history indicated hepatocellular carcinoma (HCC)
      caused by hepatitis C and liver cirrhosis during a regular hospital visit, and
      the patient had a total of 4 TAEs enforced from three years before. A 4 x 3.5 cm
      neoplasm at the left adrenal was detected by CT inspection this time. The
      diagnosis was a metastatic adrenal gland tumor from HCC. Since HCC is controlled
      by TAE, the metastatic lesions were not found in other organs and were isolated,
      of 10 cm or less in size. Hence, laparoscopic adrenalectomy was performed in
      March, 2006. He started having a meal from the 2nd day after the operation. He
      left the hospital on the 9th day. Pathologial diagnosis was a metastatic adrenal
      gland tumor from moderately differentiated hepatocellular carcinoma. When
      observing the adaptation standard strictly to the high-risk case, it was thought
      that the metastatic tumor extraction under laparoscopic surgery could become a
      low stress cure in consideration of QOL being useful as a local treatment for
      cancer.

PMID- 17212102
TI  - [A case of an elderly patient having advanced hepatocellular carcinoma with tumor
      thrombus in the inferior vena cava treated with chemo-radio-therapy-
      intraarterial infusion of weekly high dose 5-FU (WHF)].
AB  - The patient was an 81-year-old man, diagnosed with advanced huge hepatocellular
      carcinoma (HCC) with tumor thrombus extending into the inferior vena cava (Vv3),
      for which resection was judged impossible. The radio therapy (51 Gy) for tumor
      thrombus was carried out, and he received a weekly hepatic arterial infusion
      therapy (weekly high-dose 5-fluorouracil (5-FU)) for these legions. After 8
      cycles, the CT scan revealed a minor response of the tumor (SD), and,the tumor
      marker reduced. After 10 months, these legions had markedly regressed (PR), the
      tumor thrombus in the inferior vena cava was not detectable. There were no severe
      side effects. Ten months since the start of chemo-radio therapy, the positron
      emission tomography (PET) revealed a metastatic tumor of the femoral bone in
      recurrence. In conclusion, some elderly patients of advanced HCC with tumor
      thrombus may obtain a long term survival through this treatment.

PMID- 17212103
TI  - [Bronchofiberscopic treatment for malignant tracheobronchial tumor].
AB  - We evaluated bronchofiberscopic treatment for 38 cases with malignant
      tracheobronchial tumor. We performed bronchofiberscopic ethanol injection therapy
      in 13 cases, endoscopic diode laser treatment in 19 cases and airway stent
      insertion in 9 cases. Each treatment was comparatively easy and improved symptoms
      such as dyspnea effectively.

PMID- 17212104
TI  - [Neoadjuvant chemotherapy for patients with positive cytology from advanced
      gastric cancer].
AB  - Free cancer cells from advanced gastric cancer are associated with a poor
      prognosis. The aim of this study was to clarify the role of neoadjuvant
      chemotherapy (NAC) for patients with positive cytology from advanced gastric
      cancer. Thirty four patients with positive cytology and no macroscopic peritoneal
      deposits from advanced gastric adenocarcinoma at staging laparoscopy were
      studied. Gastrectomy after staging laparoscopy was performed in 9 patients
      (Surgery group). NAC following gastrectomy after staging laparoscopy was
      performed in 25 patients (NAC group). The overall response rate was 24% (CR in
      none, PR in 6, NC in 15, PD in 4). Two of the 4 patients with PD did not undergo
      surgical resection. Twenty three patients in the NAC group (resection rate 92%)
      underwent gastrectomy, which resulted in 17 R0, four R1, and two R2 resections.
      Eighteen of the 23 patients (78%) in the NAC group revealed no free cancer cells
      at operation. There was no significant deference in the overall survival curves
      between Surgery and NAC groups. Five of the 17 patients performed curative
      operation developed recurrence (peritoneum in 1, liver in]1, brain in 1, local
      and peritoneum in 1, paraaortic lymph node and peritoneum in 1). NAC for patients
      with positive cytology could lead into no free cancer cells at a high rate, but
      not to improve their prognoses. An intensive chemotherapy after gastrectomy
      should be necessary for these patients.

PMID- 17212105
TI  - [A case of complete peritonectomy for primary ovarian pseudomyxoma].
AB  - A 64-year-old woman had an abdominal distention in February 2002. She was
      diagnosed with primary ovarian pseudomyxoma. She received a hysterectomy and
      bilateral salpingo oophorectomy in April 2002. Then, she was referred to our
      hospital the same year. In October 2002, she received peritonectomy with
      resection of the hepatic capsule, diaphragmatic peritoneum, pelvic peritoneum,
      greater omentum and the spleen. Intraperitoneal CDDP administration was done on
      days 1 and 2 after peritonectomy. She is still alive without recurrence for 3
      years after the peritonectomy operation.

PMID- 17212106
TI  - [Analysis of long-term (5-year) survival in patients with metastatic breast
      cancer to the liver].
AB  - Patients with metastatic breast cancer to the liver are generally considered to
      have a poor prognosis. The purpose of this study was to identify factors
      contributing to long term survival in 11 patients who were 35 76 years old at the
      time of diagnosis with liver metastasis, and survived for 5 years. No patients
      were treated with a standard systemic chemotherapy alone. All of the 11 patients
      received OK 432 combined adoptive immunotherapy (OK-AIT), 5 underwent hepatectomy
      as an additional local therapy, and 2 were additionally treated by hepatic
      arterial infusion chemotherapy. The liver was the primary and secondary sites of
      metastasis in 8 and 3 of the 11 patients, respectively. In all of the 128
      patients given OK-AIT at 5 years after diagnosis, the 5-year survival rates with
      primary and secondary liver metastases were 11.8. and 5%, respectively. Hormone
      receptors (HR) were undetermined in 4 patients, positive in 6, and negative in 1
      patient, who was also positive for HER2. To determine the relationships among the
      prognosis of the liver metastasis, AIT indications, HR, and HER2, we analyzed our
      139 liver metastasis patients encountered in 2001 and onwards. Fifty-one patients
      with primary liver metastasis had a median survival time (MST) of 31 months, and
      a 5-year survival rate of 25%, indicating an improved prognosis. In particular, a
      MST of 50 months (n=18) in HR (+), HER2 (-) patients was in sharp contrast to the
      poor prognosis (a MST of 6 months, n=2) in HR (-) HER2 (-) patients. HER2 (+)
      patients had a MST of 27 months (n=31). Eighty-eight patients with secondary
      liver metastasis had a MST of only 11 months and a 5-year survival of only 6%;
      however, the MST in these patients showed the same tendency as in the primary
      liver metastasis patients: ER (+) HER2 (-) >HER2 (+) >HR (-) HER2 (-) (17, 13,
      and 4 months, respectively). The response rates of OK-AIT in the primary and
      secondary liver metastasis patients were 52 and 34%, respectively, showing no
      significant difference. However, there was a significant difference in the
      response rate between the HR (+) and HR (-) patients, at 52 and 12%, respectively
      (p=0.0041). Of the patients in the past, 18 with primary liver metastasis
      underwent hepatectomy in combination with OK-AIT. Of these 18 patients, 5 had
      concurrent metastases to other sites, but achieved a 5-year survival rate of 56%,
      suggesting that it is incorrect to conclude that patients with liver metastasis
      have generally a poor prognosis. Key

PMID- 17212107
TI  - [Dislocation of an indwelling catheter from digestive organs in arterial infusion
      chemotherapy].
AB  - An indwelling catheter was dislocated into the duodenum during the course of
      hepatic arterial infusion for multiple metastases of colon cancer to the liver. A
      possible cause of extravascular dislocation includes an exposure to highly
      concentrated anticancer due to defective positioning of the catheter side hole
      and bending of the catheter. A dislocation of the hepatic arterial infusion
      catheter into the digestive tract is a serious complication and accounts for 10%
      of all dislocations. Although countermeasures consisting of monitoring progress,
      laparotic catheter extraction and endoscopic catheter extraction, a monitoring
      process is selected in nearly all cases. Even though hepatic arterial infusion
      has established as being effective against liver tumors, there is a possibility
      of encountering more of these cases in the future along with an increase in the
      number of cases and a prolongation of treatment that improves prognoses. In the
      case, a catheter extravascular dislocation has occurred in addition to
      complications stemming from the dislocation itself. There was also a risk of
      exacerbation of prognosis resulting from being forced to discontinue the
      treatment. It is therefore necessary to pay close attention to positioning of the
      catheter side hole and its immobilization.

PMID- 17212108
TI  - [The efficacy of continuous hepatic arterial infusion therapy in association with
      multidisciplinary treatment of two late stage cancer patients].
AB  - With continuous hepatic artery infusion (HAI), 2 cases including multiple hepatic
      lesions became lesion free, meaning a complete response (CR) to this treatment.
      Besides chemotherapy, we controlled the diet with a healthy food guidance plan
      containing low salt & fat, and a lot of juice. The 1st case is a 63-year-old
      female, suffered from simultaneous multisided metastatic liver tumor from
      advanced rectal cancer. Four months after the low anterior resection of the
      rectum, we recommended the diet 2 months later. The patient was treated by a 24
      hour continuous HAI and the metastatic lesion disappeared (CR) within 8 weeks.
      The 2nd case is a 58-year-old male with hepatocellular carcinoma, suffered from 4
      recurrent tumors in the retained liver. After 11 treatments of HAI, the tumors
      disappeared completely, and he has survived for 11.5 years. We believe it was due
      to the immunoactivation of functional foods such as unmilled-grain, fresh
      vegetables and fruits, seaweeds, honey, and mushrooms with the restriction of
      animal fat and meat intake. Dietary guidance in metabolic-nourishment therapy is
      very useful in the treatment of far advanced cancer patients.

PMID- 17212109
TI  - [A long-term survival case of liver and mediastinal LN metastases from colon
      cancer treated with intensive multimodal therapy].
AB  - A 50-year-old man with multiple liver and mediastinal LN metastases from sigmoid
      colon cancer was admitted to our hospital in May 2005. In October 2002, a radical
      resection of the original tumor and liver metastases were performed at a previous
      hospital. Histologically, the tumor was diagnosed as Stage IV. He was treated
      with an oral anticancer agent as an adjuvant therapy. In January 2005, the CEA
      level was increased to 3.2 ng/ml and CT scan revealed a solitary liver
      metastasis. Partial resection of the liver was performed. On admission to our
      hospital, a systemic chemotherapy by FOLFOX4 was begun. The liver metastases
      showed 61% reduction in size and were judged to be PR. However, the intrathoracic
      lymph node size was not changed. Therefore, VATS extirpation of the mediastinal
      lymph node was performed. After 10 courses of FOLFOX4, abdominal CT revealed
      liver metastases remained to be almost the same size. In January 2006, radio
      frequency ablation (RFA) and partial hepatectomy were enforced and then, the
      tumor marker returned to normal. There were no serious adverse events or
      postoperative complications. He has been alive without any sign of recurrence for
      42 months from the initial treatment. In conclusion, intensive combination
      therapies for remote metastases of colon cancer might be promising to obtain a
      long-term survival without ruining QOL.

PMID- 17212110
TI  - [A long term survival case of advanced colon cancer with adjacent organ
      involvement and multiple liver metastases].
AB  - We report a long-term survival case of advanced colon cancer with adjacent organ
      involvement and multiple liver metastases. A 50-year-old man was admitted to our
      hospital because of occult bloody feces. An advanced colon cancer of the cecum
      was found with a colonoscopy. Histopathologically, it was a moderately
      differentiated adenocarcinoma with a biopsy examination. Abdominal CT showed
      advanced colon cancer with adjacent organ involvement and multiple liver
      metastases. He received right hemi-colon resection and right hepatic lobectomy.
      The patient was followed by 8 courses of adjuvant chemotherapy with 5-FU. He has
      been doing well without any recurrence for five years and six months after the
      operation. Usually the prognoses of Stage IV colorectal cancer patients are very
      unpleasant. Even thougn a few patients with Stage IV colorectal cancer can be a
      long-term survivor after multiple operations, we need to consider carefully the
      indication of the operation and QOL for a Stage IV colorectal cancer patient.

PMID- 17212111
TI  - [Two cases of multiple liver metastases from colorectal cancer which responded
      well to hepatic arterial infusion (HAI) using 5-fluorouracil and l-leucovorin].
AB  - We present two cases of multiple liver metastases from colorectal cancer, which
      did not respond to hepatic arterial infusion (HAI) using 5-fluorouracil (5-FU
      1250 mg/body weekly) alone, but responded to HAI using 5-fluorouracil (5-FU 750
      mg/body weekly) and l-leucovorin (l-LV 50 mg/body weekly) achieving a complete
      response (CR). The first case: A 71-year-old man with Stage II rectal cancer who
      underwent lower anterior resection developed multiple liver metastases 5 months
      after the surgery. As the weekly HAl using 5-FU for nine courses showed no
      response, l-LV was combined, and the liver metastases disappeared after 10
      courses to achieve CR. The second case: A 65-year-old man with rectal cancer,
      sigmoid colon cancer and multiple liver metastases underwent lower anterior
      resection. The weekly HAl using 5-FU for seven courses showed no response. By
      combining 5-FU to l-LV, the liver metastases disappeared after fifteen courses.
      No toxic event was observed. In these two cases, it was suspected that a reduced
      foliate may be responsible for the failure by the 5-FU treatment alone.

PMID- 17212113
TI  - [Effectiveness of radiation therapy to the venous thrombosis between the inferior
      vena cava and right ventricle].
AB  - In the management of hepatocellular carcinoma (HCC), a tumor thrombus occurrence
      between the hepatic vein and right ventricle is life threatening. We studied the
      effectiveness of radiation therapy to the venous thrombosis between the inferior
      vena cava and right ventricle. CASE 1: A 66-year-old man who suffered from no
      hepatic viral infection had hepatectomy of the huge HCC (over 20 cm) and
      recurrence at the post dperated liver and lung. After transarterial embolization,
      he suffered from dispnea and was found with tumor thrombus from the left hepatic
      vein to right atrium. Radiation therapy to the tumor thrombus was done and
      dispnea disappeared. He died by pneumonia at 5 months after the radiation. CASE
      2: A 74-year-old woman who had hepatecomy and RFA for multiple HCC. For the
      recurrence of HCC, TAE and RFA were performed. After the tumor thrombus in the
      inferior vena cava, mammarian cancer was found and radiation therapy was
      performed. She died after 4 months from lung edema, but no growth of tumor
      thrombus was found. CASE 3: A 79-year-old man who had TAE, hepatectomy, RFA and
      MCT for multiple hepatoma. After these treatments, tumor thrombus at the right
      ventricle was found. Although he suffered from portal tumor thrombosis, lung
      metastases, bone metastases and colon cancer after the radiation therapy, he is
      still alive at the 19 month of treatments. Radiation therapy is safe and
      effective for venous tumor thrombosis of HCC.

PMID- 17212112
TI  - [A case of high-dose rate interstitial brachytherapy for locally recurrent rectal
      cancer].
AB  - The patient was a 55-year-old female who underwent an abdomino-perineal resection
      for advanced lower rectal cancer. The tumor was a well differentiated
      adenocarcinoma, type 2 in the Japanese classification of colorectal carcinoma,
      and was measured 2.3 cm in size. Histologically, the tumor was considered to be
      stage IIIb (mp, n3(+), P0, H0, M(-)). She received adjuvant chemotherapy with 5'
      DFUR. After 13 months from the surgery, the patient developed a hip pain. After
      16 months from the surgery, a pelvic MRI scan revealed a 3 cm tumor in the
      perineum. Biopsy from the tumor revealed adenocarcinoma. Consequently, we
      diagnosed local recurrence in the perineum. Chemotherapy with CPT-11 (230
      mg/body) and 5'-DFUR (800 mg/body) was administered for 2 cycles. Because the
      tumor was enlarged, high-dose rate interstitial brachytherapy was given to the
      recurrent site at a total dose of 54 Gy/9 fractions/5 days. There were no severe
      complications. CEA was decreased within normal range from a maximum of 9.3. No
      progress was detected on CT and MRI, and the hip pain had disappeared. The tumor
      marker is within normal range for about 2 years and QOL was improved. Hence, high
      dose rate interstitial brachytherapy appears to be effective for locally
      recurrent rectal cancer.

PMID- 17212114
TI  - [A case of diffuse invasive hepatocellular carcinoma associated with thrombosis
      of the main trunk of the portal vein in which hepatic transcatheter arterial
      chemoembolization concomitant to the use of degradable starch microspheres (DSM
      TACE) was very effective].
AB  - The case reported here was a 80-year-old male who was presented with a diffuse
      type of hepatocellular carcinoma accompanied by thrombosis of the main trunk of
      the portal vein. The primary focus and portal vein thrombosis improved
      considerably following repeated transcatheter arterial chemoembolization using
      DSM (DSM-TACE). DSM-TACE was suggested to have the potential for becoming a new
      treatment method for advanced hepatocellular carcinoma, for which conventional
      transcatheter arterial embolization (TAE) using Lipiodol and so forth is
      contraindicated tue to thrombosis of the main trunk of the portal vein.

PMID- 17212115
TI  - [Efficacy of percutaneous transhepatic portal embolization for unresected cases
      of hepatocellular carcinoma].
AB  - We reported an efficacy of percutaneous transhepatic portal embolization (PTPE)
      for three patients with hepatocellular carcinoma (HCC) who did not receive
      hepatic resection. All three patients, who had HCCs in the right hepatic lobe,
      were given transarterial chemoembolization (TACE) and PTPE in the aim of hepatic
      resection. However, hepatic resection was not performed because of the refusal of
      operation or insufficient hypertrophy of the remnant liver. Primary lesions were
      well controlled by TACE in all of the cases. We recognized new HCC lesions of the
      liver in the clinical courses, but all tumors appeared to be in the post-PTPE
      area only. A possibility of prevention for transportal intrahepatic dissemination
      by PTPE was considered. We conclude that combination therapy including PTPE for
      HCC patients with tumors in the limited area is useful for the improvement of
      their prognosis.

PMID- 17212116
TI  - [MTX-CDDP-5-FU double modulation intra aortic chemotherapy for advanced and
      metastatic gastric cancer--a comparison with an intra venous route].
AB  - We studied the efficiency of MTX-CDDP-5-FU intra aortic chemotherapy for advanced
      and metastatic gastric cancer patients (n=26), and compared the results with an
      intra-venous route (n=21) of MTX-CDDP-5-FU IV chemotherapy, given the same amount
      of drugs and the same time schedule with intra-aortic chemotherapy. The response
      rate of the IA group was 39%, and that of the IV group was 50%, which shows no
      significant difference between the 2 groups. Survival curves of the 2 groups were
      identical, which show no difference. We extracted the cases which had
      retroperitoneal lymph node metastasis, and compared IA and IV groups of these
      patients. For these patients with lymph node metastasis, the response rate of the
      IA group was 41%, and that of the IV group was 55%. The survival curves were
      identical. There was no significant difference not only of the response rate but
      of the survival rate. From a drug delivery point of view, intra-aortic
      chemotherapy seems superior to intra-venous chemotherapy. But, these results
      showed no difference between intra-aortic and intra-venous routes.

PMID- 17212117
TI  - The diagnostic value of PET-CT for peritoneal dissemination of abdominal
      malignancies.
AB  - AIM: To evaluate the diagnostic value of PET-CT for predicting peritoneal
      metastasis of abdominal malignancies. METHODS: One hundred fifty four (154) cases
      of malignant tumor, including 141 cases of gastric cancer, 9 cases of colon
      cancer, 2 cases of ovary cancer, and 2 cases of pseudomyxoma, had accepted PET CT
      from Nov. 2002 to Jan. 2006. One hundred twenty three (123) had also accepted
      high speed spiral CT (HSSCT) as control. The results were compared with
      peritoneal lavage, pathological examination and clinical manifestation. RESULTS:
      The accuracy of PET-CT for peritoneal metastasis was 87.7%, with sensitivity
      72.7%, specificity 93.6%, PPV 82.1% and NPV 89.6%. HSSCT showed an accuracy of
      79.7%, sensitivity 47.4%, specificity 94.1%, PPV 78.3%, and NPV 80.0%. PET-CT had
      significantly better sensitivity than HSSCT (p < 0.05). For gastric cancer
      patients alone, PET CT had an accuracy of 87.9%, sensitivity 74.4%, specificity
      93.1%, PPV 80.6% and NPV 90.5%, significantly better than HSSCT's 78.1, 39.4,
      93.8, 72.2, and 79.2% (p < 0.01), respectively. In case of Cy1P0, PET-CT showed a
      seemingly better sensitivity of 53.3% vs. 13.3% of HSSCT, although not
      statistically significant because of the number of observations (p = 0.053). And
      in P1 cases, PET-CT and HSSCT manifested sensitivity of 84.2% vs 63.2%,
      respectively, without significance (p = 0.141). CONCLUSION: PET-CT is useful in
      predicting peritoneal metastasis of malignancies.

PMID- 17212119
TI  - [A clinical significance of direct invasion to adjacent organs in stage IV
      colorectal cancer].
AB  - We studied a clinical significance of direct invasion to adjacent organs in Stage
      IV colorectal cancer. The subjects were 19 consecutive patients who underwent R0
      surgery to the primary tumor for colorectal carcinoma, pT4, M1 1995-2003. We
      studied the relationship of pathologic invasion to adjacent organs of tumor among
      other clinicopathological factors to prognosis. Of the 19 patients, 11 (57.8%)
      had R0 surgery to the metastatic tumor. Only 4 (36.7%) patients survived more
      than 3 years. Of the 8 patients without the surgery, none of the patients
      survived more than 3 years. And the median survival time was only 8.5 months.
      Multivariate analysis indicated that RO surgery to the metastatic tumor was only
      an independent prognostic factor. The optimum resection for adjacent organs may
      prolong survival. But an extended resection is a possibility in shortening
      survival time.

PMID- 17212118
TI  - [The results of surgical treatment for pseudomyxoma peritonei].
AB  - The surgical results of 37 patients with pseudomyxoma pertonei are reported.
      Twenty eight patients received laparotomy and complete cytoreduction (CC-0) could
      be done in 6 patients. However, 13 patients received incomplete cytoreduction,
      and 9 patients underwent drainage of ascites and peritoneal washing. The
      Peritoneal Carcinomatosis Index (PCI) was less than 20 in CC-0 patients. CC-0
      patients survived significantly better than patients with residual disease.
      Accordingly, peritoneal washing to remove free cancer cells should be aimed for
      complete cytoreduction of the solid mucinous nodules.

PMID- 17212120
TI  - [A clinical study of therapy for local recurrent rectal cancer].
AB  - To evaluate the therapy for local recurrent rectal cancer, we examined
      clinicopathological characteristics and prognoses of 54 local recurrent rectal
      cancer patients. The cumulative 5 year survival rate was 20.3%, 3-year survival
      rate was 74% for a curative surgery group, 21.8% for a non-curative surgery group
      and 0% for a non surgery group. There were significant differences in the rates
      of three year survival between the curative surgery group and non surgery group,
      but there were no differences between the non curative surgery group and non
      surgery group. A survival analysis showed that prognoses of patients ew (-) or
      CEA under 10 ng/ml group were statistically better than the other group. Thirty
      four patients underwent operation. The mean operation time and the mean blood
      loss were 334.2 minutes and 1977 ml, respectively. Eighteen patients had some
      complications associated with the operation. Radiotherapy and chemotherapy did
      not contribute to improve survival rate, but contribute to improved symptoms. In
      conclusion, curative surgery is the only therapy for local recurrent rectal
      cancer to improve survival rates, but there are many complications associated
      with non curative surgery. We therefore must evaluate the indication of operation
      carefully.

PMID- 17212121
TI  - [Hepatic lymph node involvement in patients with synchronous multiple liver
      metastases of colorectal cancer].
AB  - BACKGROUND AND PURPOSE: Hepatic arterial infusion chemotherapy for unresectable
      liver metastases of colorectal cancer is generally indicated to patients without
      extra hepatic lesions. This study was performed to examine the status of hepatic
      lymph node metastasis as an extra hepatic lesion in patients with synchronous
      multiple liver metastases of colorectal cancer. PATIENTS AND METHODS: A total of
      111 hepatic lymph nodes were removed from 33 patients with synchronous liver
      metastases of colorectal cancer during resection of the primary tumor at the D2-
      or D3- level. The frequency of hepatic lymph node metastases and factors
      predictive for hepatic lymph node metastasis were examined. RESULTS: Hepatic
      lymph node metastasis was detected in nine patients (27%): The sites were
      classified into three categories: (1) along the hepatic arteries in three, (2) in
      the hepato-duodenal ligament except the peri-hepatic arterial region in three,
      and (3) both in three. The serum level of CEA (p = 0.02), CA19-9 (p = 0.05), and
      the rate of lymph node metastasis of the primary lesion (p = 0.08) were higher or
      tended to be higher in patients with hepatic lymph node metastases than in those
      without. There was no significant relationship between the involvement of hepatic
      lymph nodes and the other clinicopathologic factors examined. CONCLUSION: We
      should note the frequency of hepatic lymph node metastasis in the treatment of
      unresectable liver metastases of colorectal cancer.

PMID- 17212122
TI  - [Hepatic arterial infusion of low-dose leucovorin/5-FU chemotherapy for
      unresectable hepatic metastases from colorectal cancer].
AB  - Hepatic arterial infusion (HAI) chemotherapy for unresectable liver metastases
      from colorectal cancer (CRC) is generally indicated to patients without
      extrahepatic lesions. This study was performed to examine whether or not it was
      possible to obtain a comparable survival time, response rate (RR) and modest
      toxicity combining low-dose LV and 5-FU (LV/5-FU) with HAI for the patients with
      unresectable liver metastases from CRC. Twenty two patients with unresectable
      multiple liver metastases were enrolled in the study. These were patients who had
      been admitted from 1994 to 2003 in our hospital. Patients were given LV at 25
      mg/body immediately followed by 5-FU at 500 mg/body as a 2-hour HAI daily for 5
      consecutive days every 5 weeks. The median survival time (MST) of HAI patients
      was 24.5 months. According to the treatment in the HAI patients, one patient was
      CR, 6 were PR, 9 were NC, 6 were PD, and the response rate (RR) was 31.8% (7 of
      22 patients). The toxicities to this regimen on HAI were observed in 12 patients,
      and grades 3 or 4 were in 3 patients only. These results suggested that HAI with
      LV/5-FU can be useful for unresectable liver metastases from CRC.

PMID- 17212124
TI  - [Adjuvant hepatic arterial infusion after resection of hepatic metastasis from
      colorectal cancer].
AB  - We examined retrospectively the efficacy of hepatic arterial infusion (HAI)
      chemotherapy comparing systemic treatment as adjuvant therapy after the curative
      resection of hepatic metastasis from colorectal cancer. Seventeen cases of HAI
      and 8 of the systemic treatment were enrolled in this study. We compared the
      pattern of recurrent sites and the overall survival rate between the two groups.
      There was no difference in a patients' background. Intrahepatic recurrence rate
      was lower and extrahepatic recurrence rate was higher in the HAI group, but not
      significant. The 1-, 3-, and 5-year overall survival rate was 94, 72, and 49% in
      the HAI group and 100, 100, and 50% in the systemic treatment group (p = 0.29),
      respectively. HAI chemotherapy did not contribute to the elongation of survival
      time in comparison with systemic treatment. This study indicates that there is no
      efficacy of HAI alone after the resection of hepatic metastasis from colorectal
      cancer and that there is need to use systemic chemotherapy together with HAI to
      prevent an extrahepatic recurrence.

PMID- 17212123
TI  - [The relationship between plasma level of VEGF or soluble Flt-1 and efficacy of
      hepatic arterial chemotherapy in patients with liver metastasis of colorectal
      cancer].
AB  - PURPOSE: To clarify the clinical significance of determining plasma levels of
      vascular endothelial growth factor (VEGF) and soluble fms-like tyrosine kinase 1
      (sFlt-1) in colorectal cancer, changes in plasma levels of VEGF and sFIt 1 during
      hepatic arterial chemotherapy were investigated in patients with liver metastases
      of colorectal cancer. PATIENTS AND METHODS: The relationship between plasma level
      of VEGF or sFlt-1 and serum level of carcinoembryonic antigen (CEA), carbohydrate
      antigen 19-9 (CA19-9), or the efficacy of hepatic arterial chemotherapy was
      investigated in patients with liver metastases of colorectal cancer (n=19).
      Plasma levels of VEGF and sFlt-1 were determined by the enzyme linked
      immunosorbent assay. RESULTS: There was a positive relationship between plasma
      level of sFlt-1 and serum level of CEA (p = 0.13). The other combinations did not
      show any statistical correlations. Also, in terms of the doubling time (DT),
      there was a positive relationship between the sFlt1-DT and the CEA-DT (p = 0.04).
      The levels of VEGF tended to change in accordance with the efficacy of
      chemotherapy. In contrast, plasma levels of sFlt-1 increased in patients with the
      progressive disease, whereas the levels did not decrease in patients with the
      partial response. CONCLUSIONS: These results suggested that (1) VEGF may be a
      useful tumor marker during the chemotherapy in patients, whose CEA and CA19-9 are
      below the cutoff, and (2) the shrinkage of liver metastases may not cause a
      decrease in sFlt-1 or the half-life of sFlt-1 may be considerably long.

PMID- 17212125
TI  - [Intra arterial infusion chemotherapy combined with interferon-alpha following
      palliative hepatic resection against advanced hepatoma with portal venous tumor
      thrombus in the major trunk and multiple nodules--a preliminary study].
AB  - Recently, we reported the beneficial effects of intra arterial 5-FU infusion
      chemotherapy combined with interferon-alpha (IFN-alpha/5-FU combined
      chemotherapy) for advanced hepatocellular carcinoma (HCC). This report describes
      the preliminary results of treatment of IFN-alpha/5-FU combined chemotherapy
      following palliative hepatic resection for advanced hepatocellular carcinoma with
      tumor thrombus in the main trunk of the portal vein with multiple nodules in the
      whole liver. The 15 patients of HCC with portal venous tumour thrombi (PVTT) and
      multiple intra-hepatic multiple nodules (IM3) were treated with IFN-alpha/5-FU
      combined chemotherapy following palliative surgery in this study. No leukopenia,
      thrombocytopenia, or myelosuppression was observed in any of the 15 patients.
      Other adverse effects were, in general, clinically manageable. Concerning the
      anti-tumor effect, 6 showed an objective response and 9 showed a progressive
      disease; the response rate was 40.0% (6/15). The 1-year and 3-year survival rates
      were 48% and 21% in all 15 cases, respectively. In conclusion, IFN-alpha/5-FU
      combined therapy may be a promising modality for advanced HCC with tumor thrombi
      in the major trunk with multiple nodules after following palliative surgery.

PMID- 17212126
TI  - Destructive effect of percutaneous hydrochloric acid injection therapy for liver
      cancer--a preliminary experimental and clinical study.
AB  - OBJECTIVES: To evaluate the tissue coagulation and anticancer effects of
      hydrochloric acid compared with ethanol and acetic acid. To assess the in situ
      destructive effects and safety of CT mediated percutaneous hydrochloric acid
      injection therapy (PHAIT). METHODS: IC50 of gastric juice and 10% diluted
      hydrochloric acid against cancer cell lines in vitro were determined. Coagulated
      necrotic area of hydrochloric acid was observed in vitro and in vivo using pig
      liver. The coagulated effects of 6 mol/l hydrochloric acid solution (HAS6) on pig
      liver and muscle were compared with 50% acetic acid and anhydrous alcohol. Thirty
      patients with 38 lesions of liver cancer were treated by the CT mediated
      intratumor injection of HAS6. The in situ destructive rate, CT evaluation, PET,
      histopathology, survival and side effects were observed. RESULTS: The IC50 of
      gastric juice and 10% diluted hydrochloric acid against cancer cell lines were as
      similar as approximately 0.05-0.07% in concentration. Coagulated area of liver
      tissue by 1 ml of 1.5-12 mol/l hydrochloric acid was 18.3-53.4 mm in diameter.
      The globular hoariness coagulation area with a clear-cut borderline separated
      from normal tissue was produced. The 6.0 mol/l hydrochloric acid shows a larger
      coagulation dimension with a clear boundary, 15 times of anhydrous alcohol and 5
      times of 50% acetic acid. No toxicities in the routine local injection dosages
      were found. Clinically, the patients received 73 sessions of PHAIT; CT scan shows
      a low density area with gas that did not enhance by CT scan shown 24 hrs later. A
      good necrosis and destruction rate of cancer was obtained by PET, biopsy and AFP
      measurement. One year, 2-year and 3-year survival rates were 100, 90 and 85%,
      respectively. Nine cases survived more than 3 years, and 2 cases for more than 4
      years. No change in the heart, liver and kidney functions were found. Main side
      effects were slight pain, lower fever, etc. CONCLUSIONS: The 6 mol/l hydrochloric
      acid is an effective endogenetic protein coagulator; the cancer tissue coagulated
      effect of HAS6 was superior to 50% acetic acid and anhydrous alcohol. CT mediated
      percutaneous hydrochloric acid injection therapy showed good destructive effects;
      it would be used as a new minimum invasive treatment for percutaneous treatment
      of liver cancer, instead of acetic acid and anhydrous alcohol with its safety,
      controllability and no poisonous effects.

PMID- 17212127
TI  - [Thoracoscopic radio-frequency ablation therapy for liver surface tumor located
      under the diaphragm].
AB  - It is necessary to select a proper method for radio-frequency ablation (RFA)
      therapy of the liver tumor. Especially, treating the tumor under the diaphragm is
      usually difficult to approach by percutaneous puncture. We have done
      thoracoscopic RFA in 48 cases (43 HCC, 1 adenomatous hyperplasia, and 4
      metastatic liver tumors) to treat the tumor located on the surface of the liver
      under the diaphragma since January 1st, 2000. The average operation time was 237
      minutes, the average blood loss was 29.0 ml and the average tumor diameter were
      2.6 cm, and the average frequency of coagulation was 4.5 times. The cases which
      thoracoscopic RFA was possible with diaphragm incision were 27 cases (56%).
      However, there were 15 cases in which diaphragm incision was difficult by the
      adhesion under the diaphragm. Moreover, there were six cases with severe adhesion
      that was impossible by the thoracoscopic operation to convert an open chest
      method. There were 25 cases, which had some adhesion either in the chest or under
      the diaphragm, and those adhesions were considered to be related to the previous
      treatments such as the operation, ablation, and chemotherapy. The average length
      of the hospital stay post operation was 9.7 days. Only 3 cases (6%) needed
      additional treatments for tumor where the severe postoperative complication did
      not occur. Therefore, thoracoscopic RFA for tumor on the liver surface located
      under the diaphragm is suggested to be a feasible technique. On the other hand,
      it is necessary to pay attention to two kinds of adhesion taking a critical role
      for thoracoscopic operation procedures.

PMID- 17212129
TI  - [Low-dose gemcitabine concurrent with radiation therapy for locally advanced
      pancreatic carcinoma].
AB  - We evaluated the efficacy and feasibility of low-dose gemcitabine concurrent with
      radiation as adjuvant therapy. Nine cases of locally far advanced unresectable
      pancreatic cancer were enrolled in this study. Intraoperative radiation was
      carried out in every case using eight or ten centimeter cones with a radiation
      dose of twenty to twenty five Gy. Postoperative radiation was two Gy per day on
      weekdays for five weeks. Low-dose gemcitabine (40 mg/m2) once a week was
      administered prior to radiation. A grade 3 adverse event occurred in three cases.
      CA19-9 decreased 60.1% and DUPAN-2, 52.6%. CT scan confirmed a necrotic change
      and a decrease of the tumor size. Average survival time was ten months.
      Peritoneal dissemination was the recurrence pattern. In conclusion, low-dose
      gemcitabine concurrent with radiation therapy may contribute to local control of
      the disease. However, peritoneal dissemination must be overcome to prolong
      survival.

PMID- 17212128
TI  - [Evaluation of bronchial arterial infusion (BAI) for lung cancer with brain
      metastasis].
AB  - MATERIALS AND METHODS: Seven high risk patients of lung cancer with brain
      metastasis to which BAI was done were examined. The standard systemic
      chemotherapy was not indicated in these cases due to the patients' systemic
      condition. BAI was performed using CDDP (40-80 mg/m2)+CPT-11 (40-60 mg/m2). The
      therapeutic effects, side effects, quality of life (QOL) and prognosis were
      examined. RESULTS: All cases revealed a stable disease according to the rule of
      the RECIST. Side effects over grade 2 were not recognized. QOL was improved
      because clinical effects were recognized in all seven cases with respiratory
      symptoms (cough in 6, dyspnea at movement in 5 and hemosputum in 1). Six patients
      died three-thirty months after the treatment of brain metastasis, and the median
      survival was twelve months. The causes of death were recurrence of brain tumor in
      3, increase of primary lesion in 1, recurrence of brain tumor and increase of
      primary lesion in 2. The prognosis of the patient who had progressing T and N
      factors was bad. COMMENT: BAI was effective in keeping the quality of life for a
      lung cancer patient with brain metastasis. It was thought that BAI should be
      performed positively in the high risk patient who did not have progressing T and
      N factors.

PMID- 17212130
TI  - [A novel approach to loco-regional cancer chemotherapy with a chitosan-CDDP
      solution].
AB  - The authors applied 70% deacetylated chitin (DAC 70, chitosan) as a vehicle of
      cis-platinum (CDDP) to achieve loco-regional cancer chemotherapy, in an attempt
      to hold the drug in the target region with a locally sustained release. The DAC
      70 powder was dissolved in a 0.1 M HCI solution into where CDDP solution and
      glycerol phosphate solution were added. The resulting product, DAC-70/CDDP became
      a muco-adhesive solution. The adhesiveness between the solution and human colonic
      mucosa was measured ex vivo by our own method, and a release profile of the CDDP
      was examined in vitro using an atomic absorption method. The adhesive force was
      stronger at 37 degrees C than that of at 25 degrees C. Ten percent of the CDDP
      was gradually delivered for 6 hours, while the release was maintained at the same
      levels for the following 72 hours. The release rate increased by 10-20% when
      lysozyme was added in the incubation systems. However, the release profile of the
      drug showed no remarkable changes. The DAC-70/CDDP solution provided a favorable
      adhesiveness with human colonic mucosa, while in situ degradability of the
      solution should be improved further more.

PMID- 17212131
TI  - [A case report of small cell carcinoma of the esophagus successfully treated by
      irinotecan and cisplatin].
AB  - Small cell carcinoma of the esophagus is regarded as having a poor prognosis with
      frequent and early recurrence against various treatments. We have experienced a
      case of small cell carcinoma of the esophagus manifested by massive lymph node
      metastasis in the upper mediastinum successfully treated by CPT-11 and CDDP, and
      that a patient survived for 17 months after the initial treatment. A 62-year-old
      man underwent endoscopy due to a disturbance of the food passage. Pathological
      evaluation of biopsy specimen revealed small cell carcinoma of the esophagus. As
      he was diagnosed with bilateral lymph node metastasis in the upper mediastinum by
      CT scan, a systemic chemotherapy with CPT-11 and CDDP was adopted. After 2
      courses of chemotherapy he could be discharged as the size of the tumor was
      reduced. After 3 courses of additional chemotherapy 8 months after the initial
      treatment, a recurrent tumor was indicated at the right side of the lymph node of
      the neck. A weekly radiation with concurrent administration of docetaxel was
      carried out as a second line treatment. He is surviving for 17 months after the
      initial treatment without any evidence of recurrence. Due to histo-pathological
      similarity, a treatment for small cell carcinoma of the esophagus resembles that
      of the lung. Recently, the combined treatment of CPT-11 and CDDP was reported to
      demonstrate a better influence on a patient's survival for small cell carcinoma
      of the lung. For the esophagus, CPT-11 and CDDP was also an effective treatment.

PMID- 17212132
TI  - [A case of quadruple cancers of esophagus, stomach, lung and buccal mucosa
      improving the quality of life by loco-regional cancer therapy].
AB  - The patient is an 86-year-old man who was presented with right submandibular mass
      and tarry stool. He was diagnosed having right buccal carcinoma with right
      cervical lymph node metastasis, gastric cancer with double lesions, and suspected
      right superior lung cancer by endoscopy and computed tomography. We started with
      an operation for the right buccal carcinoma. After the operation, superficial
      esophageal carcinoma was found. Due to his old age and a lack of physical
      strength in the operation, we performed an endoscopic mucosal resection for
      esophageal cancer and argon plasma coagulation for gastric cancer. Symptomatic
      therapy was only performed for lung cancer. He died from lung cancer 18 months
      later. However, he had a good quality of life during the progress without
      recurrence, and the gastric cancer was also controllable without symptoms. It was
      difficult to decide the treatment for duplicated multiple organ cancers caused by
      numerous factors such as in our case. We assume that patient's quality of life is
      the most appropriate factor to be considered in selecting the treatment for
      elderly patients.

PMID- 17212133
TI  - [Neoadjuvant therapy with imatinib mesilate for gastrointestinal stromal tumor of
      the stomach before subsequent successful surgical resection].
AB  - A 65-year-old man is presented here with a huge mass of 13 cm in diameter in the
      left upper abdomen. Histopathologic assessment of endoscopic forceps biopsy
      revealed a c-kit positive gastrointestinal storomal tumor (GIST) of the stomach.
      Abdominal computed tomography (CT) showed a direct invasion to the pancreas.
      Imatinib mesilate was administered as neoadjuvant therapy according to the NCCN
      Guidelines. Imatinib mesilate therapy was stopped within 2 weeks because of
      adverse events such as Grade 2 of facial edema and dizziness. However, no
      hematological adverse event was shown. After three months of treatment (relative
      dose intensity was 87.5%), CT revealed a reduction in tumor diameter of 35.6% and
      showed no longer a direct invasion to the pancreas. The radical operation was
      considered feasible and partial gastrectomy was performed. The tumor was well
      encapsulated and radical surgery was possible without rupture. Adjuvant therapy
      was not performed. The patient has now been in good health without a recurrence
      for three months after the surgery.

PMID- 17212134
TI  - [A case of flat elevated type carcinoma in adenoma of the duodenum with gastric
      cancer].
AB  - Duodenal adenoma is rare, and there have been very few case reports of flat
      elevated type adenoma. We report a case of flat elevated type carcinoma in
      adenoma of the duodenum with gastric cancer. A 58-year-old man was referred to
      our hospital for gastric cancer. Endoscopic examination revealed the gastric
      cancer and a flat elevated tumor in the descending part of the duodenum,
      measuring 6 cm in diameter. The biopsy specimen of the duodenal lesion was
      diagnosed as adenoma. Distal gastrectomy and segmental partial resection of the
      duodenum were performed with no complication. Histologically, the gastric cancer
      was poorly differentiated adenocarcinoma with submcosal invasion and without
      lymph node metastasis, and the duodenal tumor was a well differentiated carcinoma
      in villous adenoma. The duodenal adenocarcinoma was limited to the mucosal layer
      and the resected margins were free of tumor. It is difficult to distinguish a
      carcinoma from a benign elevated lesion in the duodenum. Therefore, a resection
      of the whole tumor is necessary. Though endoscopic resection is the first choice
      of therapy, a surgical partial resection is necessary when it is difficult. Then,
      a segmental resection may be one of the useful procedures of surgery.

PMID- 17212135
TI  - [Improvements in quality of life and survival of patients with T4 gastric cancer
      which invaded organs after multivisceral resections through the extension of
      palliative gastrectomy and post-operative chemotherapy].
AB  - For patients with a locally advanced gastric cancer, palliative gastrectomy could
      improve local complications, such as bleeding or obstruction, but had no impact
      on prognosis. This study was designed to evaluate improvements in quality of life
      and survival of patients with T4 gastric cancer which invaded organs exhibiting
      bleeding or obstruction, after multivisceral resections of these organs through
      the extension of palliative gastrectomy and postoperative chemotherapy.
      Multivisceral resections were performed on 6 patients with T4 gastric cancer with
      local complications, such as bleeding or obstruction, at the Department of
      Surgery of Fujisaki hospital from 2003-2005. The sites of the organs invaded were
      the pancreas in five cases, and transverse colon and gallbladder in one case. The
      invaded organs were resected completely in five cases, and partially in one case.
      Surgical margins were microscopically negative in four cases. Anatomical leakage
      (sutured failure) occurred to none of the patients. All in all, the oral
      ingestion after the surgery went well. Chemotherapy (TS-1 plus CDDP) was started
      with 3 patients during their stay in the hospital. In addition, post-operative
      chemotherapy (TS-1) at the outpatient clinic was performed on 5 of the 6
      patients. More than 1 year of the performance test (PS 0 or 1 in ECOG) went well
      for 4 patients. Two of the 4 patients could resume their work. The median
      survival time was more than 419.5 days. In conclusion, we consider that
      multivisceral resections through the extension of palliative gastrectomy and
      postoperative chemotherapy for patients with T4 gastric cancer could improve
      quality of life and prognosis.

PMID- 17212136
TI  - A case report--The marked response to gemcitabine combined with irinotecan and
      low-dose cisplatin chemotherapy for advanced gastric cancer with multiple liver
      metastases.
AB  - A 69-year-old man with no sign of symptoms was admitted to our hospital for
      further examination and treatment of gastric cancer. Endoscopy revealed a
      Borrmann 3-type tumor in the cardia of the stomach. CT of the abdomen
      demonstrated a marked thickening of the stomach wall near the esophago-gastric
      junction, multiple liver metastases in bilateral liver lobes, and regional lymph
      node swelling around the cardia of the stomach. He consented and received
      systemic chemotherapy consisting of 0.5 h infusion of cisplatin (25 mg/body)
      followed by 0.5 h infusion of gemcitabine (800 mg/body) and 2.5 h infusion of
      irinotecan (60 mg/body) every 14 days as described below. Only the initial 1
      course was administered with 5-FU (500 mg/body) as an inpatient, and further
      courses were performed as an outpatient with no severe adverse events. His tumors
      responded immediately to the chemotherapy, and restaging abdominal CT after 4
      cycles of chemotherapy showed almost complete regression of liver metastases, and
      partial response to lymphadenopathy. The patient currently undergoes regular
      chemotherapy and remains in remission more than 6 months after the diagnosis of
      unresectable gastric cancer with liver metastases. It may be possible that the
      current chemotherapy will be neoadjuvant chemotherapy, and curative surgical
      resection can be performed.

PMID- 17212137
TI  - [A case of a gastric cancer patient who obtained good treatment in spite of a
      nontreatment decision].
AB  - The patient was a 57-year-old male who had received schizophrenia and alcoholism
      treatments for ten years. Hospitalization and release was repeated many times
      over in the psychiatry department of the hospital up to the present time. He
      received an upper endoscopy because of a stomach ache in May, 2004. He was
      diagnosed as having gastric cancer (L, post, Type 2, T2 (SS), N2, stage IIIA).
      Neoadjuvant chemotherapy TS-1+CDDP was begun from the beginning. However, he
      refused the operation afterwards and we changed the treatment. The chemotherapy
      was maintained until January, 2005, to enforce seven courses of the treatment and
      to maintain the long NC for about ten months. Afterwards, he refused the
      treatment again and did not come to the hospital. After six months, he came to
      hospital again for pyloric stenosis due to a stomach cancer that developed. We
      placed a PEG to keep the route for access to the pylorus in August. And we used
      it to induce the self-expandable metal stent (EMS) to the pylorus. As a result,
      oral ingestion became possible. He was able to obtain a good QOL for three months
      until dying thereafter. It is thought that stenting is one of the most effective
      treatments to correspond to the diversification of the treatment policy.

PMID- 17212139
TI  - [A partial response to combined TS-1 and docetaxel chemotherapy enabling a
      curative resection after the failure of combined TS-1 and CDDP chemotherapy in a
      patient with unresectable gastric cancer].
AB  - A 60-year-old man visited our hospital complaining of epigastric pain.
      Gastrofiberscopy revealed an advanced gastric cancer located on the anterior wall
      of the antrum. Abdominal computed tomography (CT) revealed metastases to the
      paraaortic lymph nodes. The patient subsequently underwent combined chemotherapy
      consisting of TS-1 and low-dose CDDP for the treatment of unresectable gastric
      cancer. No reductions in the paraaortic lymph node metastases were noted after
      one cycle. The patient was then treated with TS-1 combined with docetaxel as a
      second-line chemotherapy. TS-1 (80 mg/m2) was orally administered for 2 weeks
      followed by a 2 week interval, while docetaxel (25 mg/m2) was simultaneously
      administered weekly (days 1, 8, and 15). One cycle of chemotherapy was 28 days.
      An abdominal CT revealed a partial response after 3 cycles. The patient
      experienced grade 2 leukocytopenia and grade 3 neutropenia. We decided that the
      patient could undergo a curative resection, and a distal gastrectomy with D2+para
      aortic LN dissection was performed. The pathological efficacy was Grade 2. The
      patient is presently alive with no sign of recurrence after 20 months. Combined
      TS-1 and docetaxel chemotherapy is a promising second-line regimen for the
      treatment of unresectable gastric cancer, after treatment with TS 1 combined with
      CDDP has failed.

PMID- 17212138
TI  - [A case of an elderly patient with gastric cancer successfully treated with TS-1
      considering impaired renal function caused by aging].
AB  - A 75-year-old female patient with impaired renal function caused by aging was
      treated with TS 1 for gastric cancer with extensive multiple liver metastases. TS
      1 contains CDHP, which inhibits DPD activity and maintains a high blood
      concentration of 5-FU. Because CDHP is excreted from the kidney, a careful TS-1
      administration is necessary for patients with impaired renal function considering
      an occurrence of severe adverse events. Based on the result previously reported
      by us about pharmacokinetic study and recommended administration dosage of TS-1
      for patients with impaired renal function, we administered 50 mg/day of TS-1 for
      four weeks followed by two weeks rest per one course for this patient. The
      patient's creatinine clearance calculated by the Cockcroft-Gault method was 38
      ml/min, and we reduced the administration dosage in consideration of her impaired
      renal function, although normal dosage of TS-1 calculated from body surface area
      for this patient was 100 mg/day. As this patient underwent TS-1 treatment, sizes
      of multiple liver metastases and the blood concentration level of CEA were
      gradually reduced, and the reductive rate of the former was more than 90% and the
      level of the latter fell to a normal range after 12 courses of TS 1 treatment.
      Through all the treatment courses, relative drug intensity was 100% and the
      performance status of this patient was kept 0 without any grade 3 or more adverse
      events under ambulatory treatment. A successful treatment for this patient might
      indicate that it was important to consider the appropriate reduction of the
      dosage of TS-1 administration for elderly patients with gastric cancer, because
      there is a reverse correlation between aging and renal function. To clarify this
      problem, a multicenter prospective phase II study about TS-1 reductive
      administration depending on the renal function for elderly patients with gastric
      cancer (OGSG0404) is ongoing in our clinical study group (OGSG; Osaka
      Gastrointestinal Chemotherapy Study Group).

PMID- 17212140
TI  - [Two cases of inoperable gastric cancer successively treated with TS-1+CDDP as
      neoadjuvant chemotherapy].
AB  - CASE 1: A 30-year-old male with a loss of appetite and hematemesis was diagnosed
      with scirrhous gastric cancer upon detailed examination. Laparoscopic biopsy
      showed it to be Group V. Pre-operative diagnosis was T3N3P1HOM1, Stage V. Three
      courses of pre-operative chemotherapy (NAC) of TS-1+CDDP were performed.
      Laparoscopic examination as well as imaging showed a clear reduction in tumor
      size. Total gastrectomy, resection of the small intestine and cholecystectomy
      were performed. Pathological findings were type 4, por 2, pT3 (ss), ly1, v0, pN0,
      pM1 (gall bladder, small intestine): pStage IV. CASE 2: A 55-year-old male with
      epigastric pain was diagnosed with scirrhous gastric cancer upon detailed
      examination. Pre-operative diagnosis was T3N1P1H0M0, Stage IIIA. Upon surgery,
      gastro-jejunal anastomosis was performed as resection was not an optional. Three
      courses of TS-1+CDDP were performed. A clear reduction of tumor size was noted
      upon laparoscopic examination as well as imaging and distal gastrectomy was
      performed. The pathological findings shown were type 4, por 2, pT3 (ss), ly2, v1,
      pN1, p1, pStage IV. The prognosis for inoperable gastric cancer is not promising
      and there is no established treatment guideline, however, there are cases in
      which TS-1+CDDP therapy has made surgery possible, and with the anticipation of
      extended survival, can be considered a useful therapy method.

PMID- 17212141
TI  - [A case of complete remission of carcinomatous ascites refractory for TS-1
      monotherapy treated with TS-1 plus paclitaxel combined therapy for gastric
      cancer].
AB  - A 38-year-old female patient with gastric cancer, of which histological type was
      a poorly differenciated adenocarcinoma and a clinical finding was T3N1MO (Stage
      IIIA), underwent total gastrectomy with D2 lymphadenectomy as the surgical
      treatment. However, CY1 was detected during the operation and the final finding
      was T3N1MOHOPOCY1 (Stage IV). Because this surgical treatment ended in curative
      C, we administered 80 mg/m2/day of TS-1 for four weeks followed by two weeks rest
      per one course for CY1 after the surgical treatment. After two courses of TS-1
      monotherapy, extensive carcinomatous ascites appeared and blood concentration
      level of CA19-9 increased. We next treated this patient with TS-1+paclitaxel as a
      second line chemotherapy, because both of them have been reported to migrate to
      peritoneal very well and to be effective for peritoneal dissemination. The
      regimen of this combined therapy consisted of four weeks administration of TS-1
      (80 mg/m2/day) followed by two weeks rest and injections of paclitaxel (50 mg/m2)
      at day 1 and 8 for 21 days as one course. When this patient underwent TS
      1+paclitaxel combined treatment, the amount of carcinomatous ascites and blood
      concentration level of CA19-9 were gradually reduced and the former completely
      disappeared, and the latter fell to a normal range after five courses. Through
      all treatment courses, a performance status of this patient was kept 0 without a
      severe adverse event under ambulatory treatment. After 29 courses, the blood
      concentration level of CA19-9 rose again and local recurrence was detected at the
      lesion of esophagoenterostomy, though carcinomatous ascites had been kept in
      complete remission. We treated surgically for this local recurrence because of
      CY0 at the operation. At the present, 3 years and 8 months have passed since the
      first treatment started. This patient is still alive without cancer in
      ambulatory.

PMID- 17212142
TI  - [Two cases of radiofrequency ablation (RFA) therapy for control of liver
      metastases from breast cancer].
AB  - We present two cases of liver metastases from breast cancer treated by
      radiofrequency ablation (RFA) for elongation of life. Case 1: A 50-year-old woman
      was treated by left mastectomy (stage IIIa) in December 2002. In April 2004, she
      was treated with a combination therapy of weekly paclitaxel and trastuzumab for
      multiple liver metastases, left supraclavicular lymph node metastases, and
      multiple bone metastases. After 16 courses of weekly paclitaxel and trastuzumab,
      liver metastases decreased significantly in size. Because liver metastases
      recurred during a continuation of weekly paclitaxel and trastuzumab, we performed
      RFA and chemotherapy using a hepatic artery infusion of docetaxel for liver
      metastasis. The aggravation spread to the liver lesion and she died after 20
      months from liver metastases. Case 2: A 65-year-old woman was treated by left
      mastectomy (stage IIA) in 1984, and the distant metastasis was not found through
      the course after an operation. She was noted with a liver function aberration in
      another hospital in March 2005. We scanned it, and it was diagnosed as multiple
      liver and bone metastases from breast cancer. Because she did not hope for an
      anticancer drug treatment for multiple liver metastases, we performed RFA in May
      2005. After the second RFA was performed, she does not show any new lesion to the
      liver for 10 months.

PMID- 17212143
TI  - [Two cases of obstructive jaundice that developed with breast cancer hepatic
      metastasis--a treatment by a bile duct stent obtaining high efficacy].
AB  - A Treatment by a Bile Duct Stent Obtaining High Efficacy: Katsuhisa Enomoto,
      Sadao Amano and Kenichi Sakurai (Division of Breast and Breast cancer hepatic
      metastasis with icterus is poor in prognosis and an active treatment is hardly
      performed. However, we improved patients' QOL by inserting a bile duct stent as a
      topical treatment. CASE 1: A 63-year-old woman was seen having left breast
      cancer. We performed a modified radical mastectomy and axillary lymph node in
      January 1989. Since then, we continued chemotherapy and hormonal therapy. In the
      16th year after the operation, we confirmed a liver functional impairment and saw
      an increase in T-Bil to be 5.5 mg/dl. We also confirmed multiple hepatic
      metastases and intrahepatic bile duct dilation. We detained a bile duct stent and
      performed a treatment to decrease the icterus. It has been three months since the
      insertion of the stent, but we have not confirmed the rise of T-Bil. CASE 2: A 49
      year-old woman was seen having right breast cancer. We performed a modified
      radical mastectomy in June 2000. We confirmed multiple hepatic metastases in
      October 2005 and inserted a bile duct stent because we detected an expansion of
      the intrahepatic bile duct. In conclusion, it appears that a bile duct stent has
      improved patients' QOL in the cases where obstructive jaundice developed with
      breast cancer hepatic metastasis.

PMID- 17212144
TI  - [Two patients having recurrent breast cancer with brain metastases well
      controlled with a gamma knife radio-surgery].
AB  - We report two patients having recurrent breast cancer with brain metastases that
      was controlled well with a gamma knife radio-surgery. The patient is a 50-year
      old woman. She underwent radical mastectomy for right breast cancer in September
      1993. She suffered from multiple liver metastases in June 2000, so CEF therapy
      contained hepatic arterial infusion chemotherapy, and extended right lobectomy of
      the liver were performed in December 2001. Afterward, pleurodesis was carried out
      to the carcinomatous pleurisy. Then she underwent simple total hysterectomy and
      bilateral oophorectomy for torsion of the metastatic ovarian tumor. MRI study
      revealed brain metastases with a diameter of 1 cm in her right midbrain in April
      2005, so a gamma knife radio-surgery was performed. After the radio-surgery, a
      weekly paclitaxel therapy followed by peroral chemotherapy with capecitabine was
      started, and she took the regimen continuously. Another patient is a 56-year-old
      woman. She underwent skin sparing mastectomy with axillary lymph node dissection
      for right breast cancer in November 2002. Metastases to the base of her skull
      were found in October 2004, so a gamma knife radio-surgery was carried out. After
      the radio-surgery, a weekly paclitaxel therapy with anastrozole was started. In
      both of the two patients, the metastatic brain tumors have not shown growth so
      far and are under good control as of March 2006.

PMID- 17212145
TI  - [A case of advanced breast cancer with meningeal carcinomas and orbital
      metastasis successfully treated with multi-disciplinary therapy].
AB  - We report a case of advanced breast cancer with meningeal metastasis and orbital
      metastasis (T4bN3cM1, Stage IV) achieving a significant improvement in QOL by
      multi-disciplinary therapy. The patient was a 51-year-old woman who had headaches
      and an ulcerative breast lump with meningeal metastasis and orbital metastasis. A
      core needle biopsy for breast tumor led to a diagnosis of an invasive ductal
      carcinoma positive for HER2/neu protein expression. She received 9 cycles of
      weekly trastuzumab and radiation therapy for meningeal metastasis and orbital
      metastasis. Although the size of breast tumor, orbital metastasis lesion, and
      meningeal metastasis lesion exhibited no change, clinical symptoms were improved.
      One year later, she received paclitaxel so that the sensitivity of HER2/neu
      dropped. However, the tumor markers relapsed and we then changed paclitaxel to TS
      1. Eighteen-months later, she had no neurological symptoms. Multi disciplinary
      therapy can improve patient's QOL and the clinical outcomes in Stage IV advanced
      breast cancer.

PMID- 17212146
TI  - [A case of malignant fibrous histiocytoma of the buttocks].
AB  - A 67-year-old woman was admitted because of a tumor of the buttocks wall. The
      tumor was 13 x 10 x 8 cm in size, elastic hard, fixed to the gluteus maximum
      muscle. She was suspected of having a malignant tumor in the soft tissue, and the
      tumor was resected as completely as possible. After the first operation, she was
      diagnosed with recurrence of tumor in the local area a year later. After the
      second resection, she was found with recurrence of the tumor in the same area
      five years later. After the third operation, she has been doing well without any
      recurrences for five years. The prognoses of MFH are usually not so good, but
      this case could turn out to be a case of long metastasis free survival after
      local recurrences.

PMID- 17212147
TI  - [Successful treatment for intractable ascites with uterine cancer using double
      Denver peritoneovenous shunt system].
AB  - A 59-year-old woman, who underwent uterectomy for uterine cancer in February
      2000, was diagnosed having carcinomatous peritonitis with intractable ascites due
      to recurrent uterine cancer in November 2004. We conducted a peritoneovenous
      shunting at the right side of the abdominal cavity using the Denver
      peritoneovenous shunt system. A significant reduction in body weight and
      abdominal girth was seen during the follow up period. After 2 months, the
      intractable ascites was aggrayating. Because of the partition of the abdominal
      cavity by the greater omentum, the intractable ascites was dominant in the left
      side of the abdominal cavity compared with the right side. So we tried additional
      moreperitoneovenous shunting at the left side of the abdominal cavity using the
      Denver peritoneovenous shunt system. Finally, ascites and body weight were
      decreased. She was discharged from our hospital with a good quality of life.
      Double peritoneovenous shunt (Denver peritoneovenous shunt system) is a useful
      palliative treatment for intractable such as this case. Further experience and
      discussion are necessary to indicate this procedure.

PMID- 17212148
TI  - [Four cases of successful multidisciplinary treatment for hepatocellular
      carcinoma with portal venous thrombus].
AB  - CASE 1: TAI and radiation therapy were performed for a lateral segment and tumor
      thrombus extended into the left portal branch. Then, we diagnosed a tumor
      thrombus that extended into the right portal branch and TAI and operation were
      performed. The patient died about 9 months after the diagnosis of tumor thrombus.
      CASE 2: An operation was performed for hepatoma involving the right lobe and the
      tumor thrombus extended into the right portal branch. TAI and TAE were performed
      for residual tumor. The patient died about 12 months after diagnosis of tumor
      thrombus. CASE 3: An operation was performed for hepatoma involving an anterior
      segment and tumor thrombus extended into the right portal branch. Then, TAI, TAE
      and PMCT were performed for residual tumor. The patient is alive for 33 months
      with recurrence after the diagnosis of tumor thrombus. CASE 4: An operation was
      performed for hepatoma involving a posterior segment and tumor thrombus extended
      into the right portal branch. For recurrent TAI and TAE, radiation therapy was
      performed. The patient is alive for 20 months without recurrence after the
      diagnosis of tumor thrombus.

PMID- 17212149
TI  - [Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma
      providing a good QOL].
AB  - We report a case of advanced hepatocellular carcinoma (HCC). A 73-year-old man
      with positive HBV and HCV underwent a partial hepatectomy (S6 and S5) twice and
      transcatheter arterial (chemo) embolization (TAE) four times, thereafter. During
      these treatments, HCC became intractable and the patient complained of general
      fatigue. The liver function was Child's classification A, and serum AFP was 6,737
      ng/ml. Abdominal CT scan revealed recurrent lesions in the right hepatic lobe and
      left adrenal gland. The catheter for hepatic arterial infusion chemotherapy was
      inserted from the left femoral artery. Arterial chemotherapy with 5-fluorouracil
      (5-FU 750 mg) and cisplatin (CDDP 10 mg) was performed every two weeks. During 6
      courses of this regimen, a significant side effect did not appear. Abdominal CT
      revealed no change in size, but serum AFP decreased up to 794 ng/ml and the
      general fatigue subsided. After 2 months, serum AFP began to increase and became
      1454 ng/ml. The regimen of arterial chemotherapy was changed to epirubicin (EPI
      40 mg every two weeks) and UFT-E (300 mg/day for four weeks), followed by a week
      off. An appetite loss (grade 2) appeared, but it could be well controlled. Serum
      AFP decreased again, up to 54 ng/ml. A good QOL was kept for about one year after
      the initiation of hepatic arterial infusion chemotherapy.

PMID- 17212150
TI  - [A successful case of hepatocellular carcinoma with portal venous tumor thrombus
      (Vp2) treated by transcatheter arterial chemoembolization].
AB  - We reported a case of hepatocellular carcinoma (HCC) with portal venous tumor
      thrombus (PVTT) (Vp2) successfully treated by transcatheter arterial
      chemoembolization (TACE), and the tumor showed complete response and the patient
      survived for 28 months. A 67-year-old male was diagnosed with HCC in the area of
      subsegment 5 with PVTT from the P5 to the posterior branch. He was treated by
      segmental TACE. The tumor markers decreased within normal limits, and localized
      hepatic infraction in the subsegment 5 and atrophy of the PVTT were recognized.
      He survived for 28 months with no tumor recurrence after the first TACE. This
      case suggested that embolization might play a part of treatment to HCC with PVTT,
      if the liver function was preserved and the lesion of liver infraction was
      limited.

PMID- 17212151
TI  - [Surgical treatment for peritoneal dissemination of hepatocellular carcinoma
      after percutaneous ethanol injection therapy--a case report].
AB  - We report a 73-year-old man who underwent surgery for peritoneal dissemination of
      hepatocellular carcinoma (HCC) after percutaneous ethanol injection therapy
      (PEIT). He received posterior segmentectomy for HCC in 1997. Four years after the
      first hepatic resection, a recurrence lesion in the right caudal lobe of the
      liver was detected by computed tomography (CT). He underwent percutaneous ethanol
      injection therapy (PEIT) and transcatheter arterial embolization (TAE). He was
      referred to our hospital for further treatment. Abdominal CT revealed an early
      enhanced lesion (3.2 cm in size) in the right caudal lobe of the liver and an
      irregular mass lesion (1.5 cm in size) in the cranial. We diagnosed the disease
      as recurrent HCC and carried out partial hepatectomy, removal of peritoneal
      dissemination and a reconstruction of the inferior vena cava. A histological
      feature of the tumor was a moderately differentiated HCC, and there was no
      lymphatic structure in the tumor, and no connection to the residual liver.
      Therefore, we diagnosed the tumor as peritoneal dissemination of HCC. We think
      that this is a rare but a serious complication of PEIT and every effort should be
      attempted to prevent this complication, especially in the treatment of
      superficial and larger HCC.

PMID- 17212152
TI  - [A surgical case of solitary lymph node metastatic recurrence of hepatocellular
      carcinoma after hepatectomy].
AB  - The patient was a male in the sixties who received interferon therapy against
      hepatitis C. At first, the patient was pointed to having an increased alpha
      fetoprotein (AFP) level of 1104 ng/ml. Partial hepatectomy was performed against
      hepatocellular carcinoma (HCC) (segment 3, 44 mm in diameter) and diagnosed by
      further exams. The serum AFP level decreased to a normal range after hepatectomy
      for the time being. A rapid elevation of serum AFP level (11,293 ng/ml) was
      observed nine months after the surgery. No evidence of recurrence in the intra-
      and extra hepatic organs such as adrenal gland, lung, bone, and brain except for
      intra abdominal solitary lymph node metastasis was observed. Then the metastatic
      lymph node was removed surgically. After the removal of the lymph node, the serum
      AFP level decreased within a normal limit immediately. This patient currently
      survives without the disease for 30 months after the initial operation, and for
      19 months after a resection of the meatastatic lymph node.

PMID- 17212153
TI  - [A 42-month disease free survival case of combined hepatocellular
      cholangiocarcinoma with lymph node metastases treated with multimodal therapy].
AB  - Combined hepatocellular and cholangiocarcinoma (HCC-CC) is a rare type of liver
      cancer. We herein report a case of HCC-CC with lymph node metastases treated by
      multimodality therapy. The patient has been alive for more than 42 months. A 52
      year-old man with a 9 cm diameter mass lesion in the liver was admitted to our
      hospital. The tumor was diagnosed as peripheral type of cholangiocarcinoma.
      Preoperative transhepatic arterial chemoenbolization (TACE) was performed. An
      accumulation pattern of lipiodol after TACE and an increase of serum alpha
      fetoprotein led us to diagnosis of combined HCC-CC. A three segmentectomies of
      the liver and dissection of the local lymph nodes were performed. A histological
      examination of the resected specimen showed combined HCC-CC with lymph node
      metastases. Alpha fetoprotein, cytokeratins 7 and 19 were partially positive with
      immunohistochemical staining. The final diagnosis was a mixed type of combined
      HCC-CC. To improve a poor prognosis of combined HCC-CC, adjuvant chemotherapy
      with CDDP, 5 FU and radiation therapy were achieved. Fortunately, the patient is
      alive without any recurrence for 42 months after the operation.

PMID- 17212154
TI  - [A long term survival case of advanced intrahepatic cholangiocarcinoma treated
      with multidisciplinary treatment].
AB  - A 56-year-old man was admitted to our hospital for liver tumor of 7 cm in
      diameter, located mainly in the anterior segment. He underwent a hepatic
      resection of anterior and median segment of the liver in January 2002.
      Pathologically, the tumor was moderately differentiated intrahepatic
      cholangiocarcinoma (ICC) with vascular invasion. Hepatic arterial chemotherapy as
      a neoadjuvant therapy was performed. In December 2002, bone metastases in the
      12th thoracic spine and iliac bone were found. Therefore, he received
      radiotherapy (total of 30 Gy) and a monthly bisphosphonate infusion. In May 2003,
      multiple intrahepatic recurrences were diagnosed. Transarterial chemoembolization
      for twice and an additional radio-frequency ablation were performed. Four months
      later, lung metastases were found, thus, he was administered TS-1. He has been
      alive with PS 0 for 4 and half years after the hepatic resection. No new
      intrahepatic recurrences were found and bone and lung metastases remained to be
      stable. Although only a hepatic resection is a useful therapy for ICC, such a
      multidisciplinary treatment may have an effect to improve the prognosis of
      patients with ICC.

PMID- 17212155
TI  - [A case of unresectable hilar cholangiocarcinoma treated with an insertion of
      biliary stent and herbal medicine obtaining a good quality of life].
AB  - An advanced hilar cholangiocarcinoma was poor in prognosis and required a biliary
      duct drainage tube insertion to prevent jaundice. An endoscopically placed
      metallic biliary stent is efficient for improving QOL of patients with the
      disease. This case was of a 65-year-old man. He was admitted to our hospital with
      obstructive jaundice. Hilar cholangiocarcinoma was diagnosed by computed
      tomography (CT) and MR cholangiopancreatography (MRCP). Abdominal angiography
      revealed an unresectable cholangiocarcinoma through the portal vein obstruction
      and stenosis of the left hepatic artery for tumor invasion. After a second
      opinion and informed consent, he was inserted a biliary stent (non-covered
      metallic stent) under an endoscopy. The jaundice was improved further and other
      laboratory data showed normal results except for tumor markers. After the patient
      left the hospital, he came to our hospital as an outpatient basis for
      observation. He was prescribed herbal medicine from the other hospital. Now after
      ten months since the biliary stent insertion, he has been free from symptoms with
      normal laboratory data.

PMID- 17212156
TI  - [A patient with bile duct cancer who showed rapid obstruction after insertion of
      a non covered stent, but in this case obtained a stent opening and better QOL
      after reinsertion of a covered stent].
AB  - A 73-year-old man is presented with jaundice. Dynamic CT showed a papillary mass
      in the common bile duct. Percutaneous transhepatic cholangiography revealed a
      filling defect in the middle common bile duct. Poorly differentiated
      adenocarcinoma was demonstrated from a papillary mass in the common bile duct by
      biopsy specimens obtained under p. ercutaneous transhepatic cholangioscopy. Based
      on these findings, upper to middle bile duct cancer was diagnosed. An
      unresectable tumor was defined by involving the main portal vein and common
      hepatic artery at surgical exploration. A non-covered expandable metallic stent
      was placed 8 days after the operation. However, since contrast radiography showed
      tumor protrusion in the stent next day after the insertion, a covered stent was
      placed. Stent obstruction did not occur, and the patient was discharged from the
      hospital with a good quality of life. A covered stent can be more potentially and
      clinically effective than a non-covered stent especially for a papillary tumor in
      the bile duct.

PMID- 17212157
TI  - [A case of successfully treated unresectable multiple liver metastases from colon
      cancer by hepatic arterial infusion chemotherapy and systemic chemotherapy].
AB  - Sigmoidectomy was performed for a 69-year-old man with sigmoid colon cancer and
      unresectable multiple liver metastases. The histological diagnosis was
      undifferentiated carcinoma of sigmoid colon. Hepatic arterial infusion
      chemotherapy with 5 FU and systemic chemotherapy with CPT-11 were performed after
      the operation. A complete response (CR) was achieved for liver metastases. The
      recurrent sign was not found at 23 months after the operation. This combination
      therapy is expected to be an alternative treatment of colorectal cancer with
      unresectable multiple liver metastases.

PMID- 17212158
TI  - [A case of femoral artery pseudoaneurysm occurring in the site of a reservoir
      port for hepatic arterial infusion].
AB  - A 73-year-old man underwent partial hepatic resection (55) for metachronous
      metastatic liver tumor from cecal cancer in November 2005. A reservoir port for
      hepatic arterial infusion (HAI) adjuvant chemotherapy was placed in the right
      femoral artery and the HAI chemotherapy was carried out. In January 2006, he had
      swellings of the right lower leg and inguinal region and was admitted to our
      hospital for a hematoma in the site of the reservoir port and deep venous
      thrombosis. The swelling of the right lower leg went down with a bed rest in a
      couple of days. However, the hematoma of the reservoir port site was increased.
      The hematoma was removed and sutured to stop bleeding and then compression
      homeostasis was applied for a week. An enhanced pelvic CT scan showed a
      pseudoaneurysm in the femoral artery and an impending rupture was suspected. He
      was immediately referred to a vascular surgeon and underwent emergency surgery.
      Intraoperative angiography showed a pseudoaneurysm, 2.5 cm in diameter, in the
      femoral artery. An approximate 1 cm tear around the catheter insertion site was
      found and a primary suture was performed. A rapid diagnosis and treatment are
      required when a pseudoaneurysm is suspected during HAI chemotherapy.

PMID- 17212159
TI  - [Utility of arterial infusion chemotherapy and radiation therapy for the pelvic
      local recurrence of rectal cancer].
AB  - We treated 3 cases of local pelvic recurrence due to a rectal cancer post
      operation by arterial infusion chemotherapy with 5-FU and levofolinate calcium
      and also by radiation therapy. The result of imaging analysis showed that a
      recurrent tumor was decreased effectively in 2 cases by chemo-radiation therapy.
      We confirmed the cancer pain and tumor bleeding were gone for all of the 3 cases.
      As for side effects of arterial infusion chemotherapy and radiation therapy, we
      confirmed a paralysis of the pelvic nerve in 1 case and dermatopathy in 1 case.
      This therapy seemed to be an effective treatment for elderly patients with
      inoperable cases.

PMID- 17212160
TI  - [A treatment for pulmonary metastases from colorectal cancer by pre-operative CPT
      11/5'-DFUR combination therapy].
AB  - There is no standardized consensus at each institution about a treatment for
      pulmonary metastases from colorectal cancer. A case of pulmonary radical
      resection can expect a good result. However, a result of a nonoperative case is
      extremely poor. A focal control until the time of operation to a metastatic
      lesion is very important. We want to have a safe and effective chemotherapy. We
      experienced a resectable case by CPT-11/5'-DFUR combination therapy.

PMID- 17212161
TI  - [A case of colon cancer liver metastases treated by combined therapies].
AB  - A 46-year-old male patient underwent sigmoidectomy with D2 lymph node dissection
      and partial resection of the bladder for advanced colon cancer in January 2000.
      The lesion was judged to be pT2, pN0, sP0, sH0, sM0 and Stage II, and the patient
      was treated on a regular schedule as an outpatient. Fourteen months after the
      first operation, liver metastases (S4, S5) were found and partial resections of
      the liver were performed. However, a recurrence had often been detected in the
      residual liver for five years afterwards. Liver resections had been repeated for
      four times before radiofrequency ablation was performed in January 2005. The
      patient received adjuvant chemotherapy with 5'-DFUR, 5-FU/l-LV (RPMI method), and
      TS-1. In January 2006, obstructive jaundice due to tumor growth occurred and a
      self-expandable metallic stent was placed in the narrowed portion of the
      intrahepatic bile duct. The patient is,currently undergoing FOLFOX4 and FOLFIRI
      regimens.

PMID- 17212163
TI  - [Successful surgical treatments for pulmonary and/or hepatic metastases after
      surgical resection for colorectal cancer--two case reports].
AB  - In colorectal cancer, hepatic and pulmonary metastases are the most common and
      most important prognostic factors. Surgical resection is the first choice of
      treatment for hepatic and pulmonary metastases if completely resectable. However,
      only a few patients survived long term after metastatectomy. We present the two
      cases, in which surgical resection for pulmonary and/or hepatic metastases from
      colorectal cancer resulted in long-term survival for more than ten years without
      recurrence.

PMID- 17212162
TI  - [A case of apocrine adenocarcinoma suspected as an axillary lymph node metastasis
      from cecal cancer].
AB  - The patient was a 69-year-old male. He had a 2-year history of subcutaneous tumor
      in the left axilla. Biopsy of the tumor showed the features of metastatic
      adenocarcinoma. FDG PET to check the primary lesion revealed the collection of an
      ileocecal junction and left axilla. After CT scan and colonoscopy, we diagnosed
      cecal cancer and metastasis of the axillary lymph nodes from it. He underwent
      ileocecal resection and a wide local resection of the axillary tumor.
      Histopathological examination showed the axillary tumor was different from the
      cecal cancer. Axillary tumor was diagnosed not as metastasis of axillary lymph
      nodes from cecal cancer but apocrine adenocarcinoma.

PMID- 17212164
TI  - [Sigmoid colon cancer with a tumor thrombosis in the splenic vein--a case
      report].
AB  - A 63-year-old woman was admitted to the hospital for investigation of abdominal
      discomfort. Further examination revealed that she had sigmoid colon cancer. The
      serum CEA level was 20.1 ng/ml, and the CA19-9 level was 8.9 U/ml. Laparotomy
      findings showed H0, P0, and lymph-nodes swelling observed at LN253-LN16b2.
      Massive tumor thrombosis was present in IMV, the splenic vein, and the advanced
      region in the portal vein. Metastatic tumor was present in the pancreas body. An
      anterior resection of the colon combined with resection of lymph nodes, pancreas
      body and tail and spleen were performed. Resection of IMV and splenic vein
      including tumor thrombosis was performed prudently. Histological examination
      revealed that the pancreas tumor and tumor thrombosis were of the same origin
      (moderately differentiated from adenorarcinoma), and massive LN metastases
      existed. Post operative chemotherapy, an oral administration of UFT/UZEL, was
      performed. After 24 months of operation, there has been no sign of recurrence
      detected.

PMID- 17212165
TI  - [A case of effective chemoradiation therapy against anal fistula carcinoma
      recurred 10 years after surgery].
AB  - A male in his eighties underwent abdominoperineal resection under the diagnosis
      of adenocarcinoma associated with anal fistula (P0, H0, n (-), A1, stage II, ly0,
      v0). Ten years after the surgery, a painful lymph node swelling was noticed in
      the left inguinal region. Biopsy specimen showed adenocarcinoma consisting of
      severe dysplastic cells. Radiotherapy was performed in the pelvic region at a
      total dose of 50 Gy (2 Gy/day). After the radiotherapy, left inguinal and pelvic
      lymph nodes markedly shrank and became painless. After one month, the
      chemotherapy with UFT (UFT 300 mg/day) was started. One year thereafter, para
      aortic lymph nodes were found to be enlarged, but a good quality of life was
      obtained without elevation of tumor markers.

PMID- 17212166
TI  - [A case report of successful local control with chemoradiation for unresectable
      rectal cancer].
AB  - We report a patient with a case of advanced rectal cancer with unresectable liver
      metastasis, who received the combination of systemic chemotherapy of 5-FU/l-LV
      and external radiation therapy. He was alive for 21 months. He had been able to
      maintain a good quality of life without any complaints of the primary rectal
      tumor.

PMID- 17212167
TI  - Medication therapy in ambulatory medical care: United States, 2003-04.
AB  - OBJECTIVE: This report describes medication therapy at visits to physician
      offices, hospital outpatient departments, and emergency departments in the United
      States during 2003 and 2004. Office-based care is further subdivided into three
      categories-primary care, surgical specialties, and medical specialties. METHODS:
      Data from the 2003 and 2004 National Ambulatory Medical Care Surveys (NAMCS) and
      National Hospital Ambulatory Medical Care Surveys (NHAMCS) were combined to
      produce averaged annual estimates of ambulatory medical care utilization.
      RESULTS: An estimated 1.9 billion drugs per year were provided, prescribed, or
      continued at ambulatory care visits in the United States during 2003 and 2004.
      Two-thirds of the 1.1 billion ambulatory care visits per year included medication
      therapy. The rate was highest at visits to medical specialists (2.3 drugs per
      visit). The rate of drugs per visit increased with patient age in each ambulatory
      care setting. Cardiovascular-renal was the class of drugs most frequently cited
      at visits to primary care physicians and medical specialists. Pain relievers were
      the drugs reported most often at hospital emergency and outpatient department
      visits. Of the 50 drugs most frequently reported overall, three-quarters of them
      were accounted for by six therapeutic classes-pain relievers, cardiovascular
      renal agents, respiratory tract drugs, central nervous system drugs (antianxiety
      agents and antidepressants), hormonal agents, and antimicrobials. Ibuprofen,
      aspirin, atorvastatin calcium, acetaminophen, and albuterol were the five most
      frequently reported medications. From 1993 to 2004, the number of drugs provided,
      prescribed, or continued per visit increased for all settings.

PMID- 17212169
TI  - Safe in our care?

PMID- 17212173
TI  - A new emergency care nursing role.

PMID- 17212172
TI  - The secrets of success.

PMID- 17212174
TI  - Intraoral ranulas.

PMID- 17212175
TI  - Scissors: an infection risk?

PMID- 17212176
TI  - Early pregnancy loss.

PMID- 17212177
TI  - The Glasgow Coma Scale: clinical application in emergency departments.

PMID- 17212178
TI  - Board's eye view. Identity theft.

PMID- 17212179
TI  - Value of health care expenditures.

PMID- 17212180
TI  - Roux-en-Y gastric bypass, Nesidioblastosis and diabetes mellitus.

PMID- 17212181
TI  - Infarcted epiploic appendage of the vermiform appendix masquerading as acute
      appendicitis.
AB  - Infrequent causes of right lower quadrant pain that mimic acute appendicitis
      include infarcted epiploic appendages. Although usually located in the colon, we
      report the very rare case of an infarcted epiploic appendage located directly on
      the serosal surface of the appendix itself. In a patient with right lower
      quadrant pain, the diagnosis of infarcted epiploic appendages is rarely made
      preoperatively and the incidence is rare. Definitive treatment is excision.

PMID- 17212183
TI  - DAKOTACARE update: 2007 initiatives.

PMID- 17212182
TI  - Clostridium difficile-associated disease.

PMID- 17212184
TI  - Extenuating circumstances: regarding comfort one: new cardiopulmonary
      resuscitation directives in South Dakota.
AB  - Circa 2001, Aunt Abby had reached her seventh decade when she was diagnosed with
      advanced ovarian cancer. Chances of cure were slim to nil, and true to her
      Midwestern upbringing and staunch faith that a better world awaits, Aunt Abby
      chose to live out her last months at home, "doing" for Uncle Bill, as she had for
      the last fifty-two years. Uncle Bill and the kids understood and were willing to
      abide by her wishes to just let her pass, as God would will. But, when the day
      came that Aunt Abby's heart failed, she was puttering through the local grocery
      alone, while Uncle Bill slipped around the corner to pick up parts from the
      hardware store. An alert store clerk called 911. The EMS team arrived quickly,
      and, as their protocol required, began resuscitation. Aunt Abby's wish for a
      death with "no fuss" was no match for the emergency medical system's clinical and
      legal duty to treat until a physician ordered otherwise.

PMID- 17212185
TI  - A doctor's story.

PMID- 17212186
TI  - Pneumococcal conjugate vaccine. What you need to know.

PMID- 17212187
TI  - [Early psychological interventions in children after trauma].
AB  - Early psychological interventions within the first hours, days or weeks after a
      traumatic event aim to avoid or minimize middle- or long-term mental-health
      problems. To date, there are no articles in German language available that review
      the field of early psychological interventions in children. This paper defines
      this field, summarizes current early psychological interventions and reviews the
      literature on effectiveness of early interventions. Most of the early
      psychological interventions in children after trauma that are reported in the
      literature are not evidence based. Moreover, current knowledge is limited by a
      number of methodological problems. First, most studies have no control groups and
      the samples are small. Second, different timeframes and interventions complicate
      a comparison of different studies. For future research, randomised controlled
      studies with manualised interventions and repeated follow-ups are demanded. In
      clinical practice, the lack of studies on effectiveness of early psychological
      interventions in children leads to a simple transfer of intervention strategies
      from adults. This practice needs to be questioned. Importantly, the consideration
      of developmental aspects is crucial. To date, no evidence-based advise can be
      given with regard to early psychological interventions in children. Moreover, it
      remains unclear, how to involve the parents.

PMID- 17212188
TI  - [Parental presence and parental coaching in non-violent resistance].
AB  - Parental Presence (PP) and Non-violent Resistance (NVR) are the core concepts to
      describe an approach in counselling helpless parents of children with behavioral
      disorders. Basically PP means the presence of the parents in the life of their
      child. It can get lost when escalating conflicts so much become part of the
      everyday life of the family that these processes can't be handled constructively
      any more. The escalation then follows either a pattern of complementarity--the
      readiness of the parents to easily give in, or a symmetric pattern of increasing
      mutual hostility. Parents then often withdraw and thus parental helplessness and
      loss of PP come along with each other. The program of systemic parental coaching
      in NVR has been developed by Haim Omer in Tel Aviv, Israel, and attracted
      increasing attention among experts in Germany in the last years. It provides an
      opportunity for the parents to find a "third way" between the two escalating
      patterns and regain their presence. The approach is described, and the
      interventions are explained.

PMID- 17212189
TI  - [Stigmatization of language impaired children from the parents' perspective].
AB  - Stigmatization can strongly affect the social integration of children and
      adolescents with developmental and behavioral disorders. The goal of the study
      was to investigate negative and positive labeling of speech-language impaired
      children as perceived by their parents. We analyzed 386 parental questionnaires
      on stigmatization by and support from other children, family members and other
      adults. Half of the parents reported stigmatization of their child. They
      perceived negative labeling and exclusion most frequently in the child's peer
      group, but also among family members. Support was more common than negative
      labeling, however. There was a strong positive relationship between negative
      labeling and behavioral problems. Parents of children with developmental and
      behavioral disorders often perceive stigmatization of their child. Therefore, in
      counseling such families child and adolescent psychiatrists should address this
      issue adequately and recommend appropriate coping strategies.

PMID- 17212190
TI  - [Influencing factors on the course of supervised visitations in a parental
      counselling office].
AB  - We report about a youth welfare service tool called supervised visitation (SV).
      SVs are intended to maintain contact and emotional relationship between child and
      absent parent. In the present study, we assessed a number of supposed influencing
      factors on course and result of SV. 55 % of the SV cases could eventually be
      transferred to regular contact without supervision. The majority of SV cases
      could be finished after a couple of months. The number of accompanying
      counselling sessions was often higher than the number of SVs themselves, a result
      stressing the significance of counselling. Younger as well as older children did
      benefit from SV. Opposed to some of the literature, in our study the success of
      SV did not depend on kind of referral or custody, specific indications, or the
      length of contact interruptions. We found a tendency though that a high number of
      risk factors is a potential risk for SV success.

PMID- 17212191
TI  - [Hypertension in Croatia--where are we?].

PMID- 17212192
TI  - [Treatment and control of hypertension in Croatia. The BEL-AH study].
AB  - Poor control of blood pressure (BP) is one of the main reasons for high
      cardiovascular mortality and morbidity. The aim of this study was to analyse
      control of BP in outpatient settings in four biggest towns in Croatia. The study
      included 412 medical doctors (GP) and 7031 middle-aged patients (62.9 +/- 11.5
      years). Mean BP in treated patients was 162.9 +/- 16.8/95.6 +/- 9.9 mmHg. There
      were no statistically significant differences in systolic (p = 0.173) and
      diastolic (p = 0.561) BP between men and women. In this group of patients only 8%
      achieved target BP values. In contrast, and surprisingly, 44.5% of medical
      doctors and 72% of patients were satisfied with obtained BP control. Higher
      percentage of male patients vs. female were satisfied with blood pressure control
      (81.9%:66.9%). BMI < 25 was registered in 22.9% of hypertensive patients, and
      there was statistically significant difference in BMI between men and women (chi2
      = 56.769, p < 0.001). In this study we found a statistically significant
      difference of hypertension in regard to BMI in both sexes (chi2 = 46.339, p <
      0.001; chi(z)2 = 45.992, p = 0.024). BMI was in correlation with severity of
      hypertension as well as with obtained treatment result. BMI was in correlation
      with the number of prescribed drugs. According to this, patients with BMI < 25
      were prescribed less drugs than those with BMI > 30 (1.4:1,6 p = 0.001). BP
      control in Croatia is, according to this study, very poor. The main reason for
      such situation is, beside obesity which determines the stage of hypertension and
      BP control in both sexes, insufficiently developed conscience in patients and
      doctors about the importance of stronger blood pressure control. The results
      indicate the necessity for the more intensive education of the population.

PMID- 17212193
TI  - [Metabolic syndrome in patients with hypertension].
AB  - Metabolic syndrome is a constellation of interrelated abnormalities that increase
      the risk for the development of cardiovascular disease and type 2 diabetes.
      Together with obesity and dyslipidaemia, hypertension is one of the basic
      elements of the metabolic syndrome. Current guidelines do not provide specific
      recommendation for pharmacological management of the hypertensive patients with
      metabolic syndrome. Recent trials have consistently shown that therapy involving
      beta-blockers and diuretics may have some negative impact on metabolic and
      haemodynamic disorders present in metabolic syndrome. Several lines of evidence
      support the use of angiotensin-converting enzyme inhibitors, or angiotensin
      receptor blockers as the appropriate first-line therapy and calcium channel
      blockers, as the second, in the patients with metabolic syndrome.

PMID- 17212194
TI  - [Antihypertensive agents and the risk of new onset diabetes mellitus].
AB  - Arterial hypertension is frequently associated with type 2 diabetes mellitus, and
      both of these diseases are the major risk factors for cardiovascular
      complications. During the past few years, a number of large randomized clinical
      trials examined the frequency of new onset diabetes mellitus during
      administration of antihypertensive drugs. Application of ACE inhibitors or
      angiotensin receptor blockers reduces the risk for the onset of diabetes mellitus
      by 20-27%, and calcium channel blockers by 16%. Despite some uncertainties, novel
      studies have demonstrated an increased risk for cardiovascular complications
      related to new onset diabetes mellitus. The duration of patient monitoring is
      also an important factor, as the onset of diabetes-related complications is
      closely associated with the duration of this disease. Considering all above, the
      aim of preventing the onset of diabetes is to recognize patients with an
      increased risk. The risk factors include basal glycemia, positive family history
      for diabetes mellitus, obesity, metabolic syndrome, and some ethnic groups (South
      Asia, the Caribbeans). Therefore, increased-risk patients should be subjected to
      therapy with ACE inhibitor, angiotensin receptor blocker, or calcium channel
      blocker as the first drug of choice. For these patients, application of thiazides
      and beta blockers or the combination of these two drugs is not advantageous.
      However, such a view poses a dilemma whether thiazide diuretics should be the
      first choice in the treatment of hypertension.

PMID- 17212195
TI  - [Antiatherosclerotic effects of antihypertensive drugs].
AB  - Arterial hypertension is one of the leading causes of atherosclerosis. Many
      studies of antihypertensive drugs have been recently focused on prevention,
      stopping and if possible regression of atherosclerosis. Some antihypertensive
      drugs which are used in clinical practice have antiatherosclerotic effects
      besides their effects on the reduction of systemic blood pressure. Oxydative
      processes and oxygen free radicals participate in the pathogenesis of
      atherosclerosis. The concentration of oxygen free radicals is increased in
      patients with arterial hypertension. Antioxidant could neutralise oxygen free
      radicals. There are endogenous antioxidants like vitamin E, vitamin C etc. Some
      antihypertensive drugs have antioxidant properties and they could neutralise free
      oxygen radicals. These drugs are: calcium channel blockers, ACE-inhibitors, beta
      blocker carvedilol and blocker of alpha-receptors-doxazosine. Antiatherosclerotic
      effects of these drugs have been shown in experiments in vivo, in animals as well
      as in clinical studies. The results of the most important clinical studies will
      be presented in the following text.

PMID- 17212196
TI  - [Chronic kidney disease and statins].
AB  - Dyslipidemia is a risk factor for de novo occurrence of renal disease in
      apparently healthy population, and diabetes, and contributes to progressive
      decline of renal function in diabetic and nondiabetic kidney disease. Chronic
      kidney disease and dyslipidemia, frequently occurring together, are independent
      cardiovascular risk factors. There is a strong association between the level of
      renal insufficiency and cardiovascular disease. According to available evidence,
      statin therapy may reduce cardiovascular risk in chronic kidney disease as well
      as modify its course, especially in patients with moderate impairment of renal
      function. However, all these findings must be examined in large-scale trials in
      patients with chronic renal disease and different stages of renal insufficiency.
      There are several on-going trials aimed at determing the role of statin therapy
      in this specific population, and confirming its efficacy in reducing
      cardiovascular risk and halting the progression of chronic kidney disease.

PMID- 17212197
TI  - [Treatment of hypertension in acute neurological diseases].
AB  - Continuous brain blood supply in healthy individuals is warranted by brain
      autoregulation, the borders of which are not completely strict and can be changed
      as a part of dynamic physiological control. In acute neurological diseases like
      hypertensive encephalopathy, brain infarction, intracerebral hemorrhage and
      subarachnoid hemorrhage, a great attention should be paid to cerebral perfusion
      pressure preservation (which represents a difference between mean arterial
      pressure and intracranial pressure) when blood pressure is regulated. To preserve
      neurological function it is necessary to know anatomic and pathophysiological
      qualities of brain circulation and to approach the treatment of hypertension. In
      case of ishemic stroke hypertension should be reduced gradually, through several
      days, having in mind the distance of ischemic penumbra. The ideal
      antihypertensive for the reduction of hypertension in acute neurological diseases
      should have the following characteristics precise value and time control of blood
      pressure, not to have a rebound-phemonenon, not to cause the effect of exceeding
      with initially severe hypotension, not to have impact on heart muscle and not to
      worsen intracranial pressure. In everyday clinical work with these patients one
      should act according to the instructions for management of patients with stroke
      prepared by the Croatian Society for Neurovascular Disorders of the Croatian
      Medical Association and the Croatian Society for the Prevention of Stroke.

PMID- 17212198
TI  - [Hypertension in pregnancy].
AB  - Pregnancy in hypertension is not a single entity, and currently several
      classifications exist. Most often used is the updated classification of the
      American College of Obstetricians and Gynecologists, which classifies
      hypertension into chronic hypertension, preeclampsia-eclampsia, preeclampsia
      superposed on chronic hypertension, and gestational hypertension. Preeclampsia
      occurs in about 7% of pregnant women. Primigravida have increased risk for
      preeclampsia. Preeclampsia frequency in sisters was 37%, in daughters 26%, in
      granddaughters 16%, an in daughters in law only 6%, which points to the strong
      hereditary association. Although basic clinical changes in preeclampsia appear in
      the second part of pregnancy, some haemodynamic and biochemical abnormalities may
      be observed earlier. Besides haemodynamic abnormalities in the mother, one of the
      main characteristics of preeclampsia is uteroplacental circulation insufficiency,
      and consequent intrauterine growth restriction. Basic alterations in preeclampsia
      occur due to inadequate trophoblast migration and lack of spiral artery
      physiologic transformation. In preeclampsia, musculoelastic layer of spiral
      arterioles is preserved, therefore their lumen stays narrow during the entire
      pregnancy, ad their wall sensitive to vasoconstrictive factors. Currently, the
      most convincing and most comprehensive is the hypothesis on generalized
      endothelial dysfunction as the underlying pathophysiological mechanisms.
      Preeclampsia is an illness that develops due to vasoconstriction and reduced
      perfusion, particularly in essential organs. HELLP syndrome is a multiple system
      disease whose pathogenesis has not yet been completely explained. In HELLP
      syndrome endothelial vascular cells are damaged, resulting in intravascular
      platelet activation. Frequency of HELLP syndrome is about 0.2-0.6% of all
      pregnancies, and 4-12% of those with preeclampsia. HELLP syndrome is an acronym
      for H = haemolysis, EL = elevated liver enzymes and LP = low platelet count. Risk
      factors are multiple pregnancy, mother' age over 25 years, white race, and poor
      perinatal outcome in previous pregnancies. Preeclampsia treatment is a great
      challenge for every physician, but also the subject of numerous discussion
      because there is no consensus on which drug would be the best for the treatment
      and prevention of preeclampsia. Generally accepted opinion is that the cut-off
      blood pressure level, when antihypertensive therapy should be initiated, is
      diastolic blood pressure over 110 mmHg. However, it should not be decreased below
      90-100 mmHg in order not to jeopardize uteroplacental circulation, which is in
      preeclampsia and eclampsia already significantly reduced. Termination of
      pregnancy is the definitive treatment for preeclampsia and eclampsia.

PMID- 17212199
TI  - [Regulation of blood pressure in dialyzed patients].
AB  - Up to 90% of chronic haemodialysis patients have blood preasure (BP) greater than
      140/90 mmHg. This suggests that only a minor number of the haemodialysis patients
      have adequate BP control. This is associated with significantly increased
      morbidity and mortality in haemodialysis population when compared with normal,
      healthy population. The main aim of antihypertensive treatment in hypertensive
      haemodialysis patients is to achieve BP values which should not differ from those
      recommended for general population. The most important factor in BP regulation in
      haemodialysis patients is adequate fluid volume regulation. Sympathetic nervous
      system and impaired vasodilatation with consequent changes in peripheral vascular
      resistance, secondary hyperparathyreoidism and its effects on calcium balance and
      consequent effects on cotractility of the smooth muscle cells of the vessel wall,
      correction of renal anemia in patients receiving human recombinant
      erythropoietin, regulation of salt intake, and frequency and duration of
      haemodialysis procedure have also a significant role in BP regulation in these
      patients. If dialysis procedure is not adequate, meaning that salt and water
      balance is not satisfyng, antihypertensive medications cannot alone control BP in
      haemodialysis patients.

PMID- 17212200
TI  - [Hypertension after kidney transplantation].
AB  - Cardiovascular disease (CVD) is the leading cause of death among renal transplant
      recipients. The prevalence and severity of CVD in renal transplant recipients are
      related to numerous factors, most shared with the general population and others
      specific to transplant recipients, including effects of kidney dysfunction and
      immunosuppressive drugs. Arterial hypertension is highly prevalent after renal
      transplantation and may contribute to the risk of cardiovascular disease and
      graft failure. Immunosuppressive drugs such as corticosteroids, cyclosporine and
      tacrolimus may be important contributing factors to post-transplant hypertension.
      Recent data suggest that renal transplant patients under tacrolimus-based therapy
      showed less arterial hypertension compared with cyclosporine treated patients.
      New immunosuppressive drugs, including mycophenolate mofetil and sirolimus, are
      not nephrotoxic, do not have any hypertensive effect and may permit several
      combinations that offer important alternatives to classical immunosuppressive
      regimens to reduce the incidence and clinical impact of arterial hypertension
      after renal transplantation. Other metabolic disorders, such as post-transplant
      dyslipidemia and diabetes have to be closely monitored and treated as soon as
      possible. Incidence of arterial hypertension after kidney transplantation may be
      reduced by early detection, proper adjustment of immunosuppressive protocols and
      aggressive treatment with lifestyle modification and potent antihypertensive
      drugs.

PMID- 17212201
TI  - [Hypertension in patients with renal transplantation].
AB  - Hypertension frequently occurs in patients with renal transplant. The aim of the
      present study was to determine the incidence, time of occurrence and hypertension
      severity following transplantation. A total of 78 patients (37 women and 41 men)
      mean age 49.9 +/- 12 years were included in the study. The post-transplant period
      amounted from 6 to 168 months. Prior to transplantation, hypertension was
      registered in 14 patients (17.9%). Following transplantation hypertension was
      registered in 59 (75.6%). During the first post-transplant year hypertension
      occurred in 79% of patients, while in the period of one to three years in 13.5%
      and in 6.7% of patients with transplant performed three or more years earlier.
      Hypertension responsive to only one drug was found in 22%, and to two or more
      drugs in 25% of patients. The satisfactory blood pressure values were obtained in
      78% of patients. The study reveals that hypertension in the majority of renal
      transplant patients develops during the first post-transplant year.

PMID- 17212202
TI  - [Arterial hypertension in patients on long-term haemodialysis].
AB  - Arterial hypertension is one of the most frequent causes of chronic kidney
      failure but also one of most frequent complications in patients on long-term
      haemodialysis. The aim of this work is to investigate the prevalence of arterial
      hypertension in long-term haemodialysis patients, and methods for treating it. A
      total of 168 patients (86 women and 82 men average age 62.9 +/- 12.9 years) from
      three dialysis centers were included in this study. Arterial hypertension was
      defined as blood pressure immediately before hemodialysis > 140/90 mmHg or less
      if the patient has been on anti-hypertensive therapy. Before the beginning of a
      long-term hemodialysis program arterial hypertension was registered in 139 (81%)
      patients. The patients were on haemodialysis 52.5 +/- 45.17 months. All patients
      were dialyzed three times per week, an average of 11.7 hours per week (9 to 13.5
      hours). Body weight of the patients was 68.4 +/- 15.8 kg, and weight gain between
      dialysis treatments was 2.9 +/- 1.1 kg. Arterial hypertension was recorded in 141
      patients (84%), i.e. average blood pressure before haemodialysis in all patients
      was 157.3 +/- 17.3/85.2 +/- 8 mmHg. The average blood pressure of the remaining
      patients was 132.6 +/- 8.2/ 78.3 +/- 10.3 mmHg. The patients were treated with a
      variety of anti-hypertensive drugs. Thirty-seven patients were on monotherapy,
      while the others were on combined treatment (2-4 antihypertensive drugs). The
      most frequently used antihypertensive drugs were calcium channel blockers (95
      patients, or 67%), ACE inhibitors (47 patients, or 33%), beta-blockers (29
      patients, or 20%), angiotensin II receptor blockers and alpha-blockers (25
      patients, or 17%), diuretics (11 patients, or seven percent), and nine patients
      (6%) received central agents or drugs wich acted like an alpha+beta blocker.
      Prevention and treatment of arterial hypertension is a special problem for
      haemodialysis patients. Unfortunately, there are still no guidelines for the
      optimal method of measuring blood pressure in these patients, or optimal values
      of arterial blood pressure, the first drug of choice or optimal combination of
      therapies. Perhaps because of this cardiovascular morbidity and mortality among
      these patients is high.

PMID- 17212203
TI  - [Laparoscopic treatment of functioning adrenal tumors].
AB  - INTRODUCTION: Laparoscopy is now a widely used method for removal of functioning
      and non-functioning adrenal tumors. This paper reports our experience in
      laparoscopic transperitoneal removal of functioning adrenal tumors including
      pheochromocytoma, Cushing's disease and aldosteronoma. METHODS: Between May 2001
      and April 2006, 29 patients underwent laparoscopic adrenalectomy for
      pheochromocytoma. In 37 patients (10 patients with bilateral adrenalectomy)
      adrenalectomy was performed for Cushing's disease, while 28 patients had
      aldosteronoma. In 2 patients adrenalectomy was performed for virilizing adenoma.
      RESULTS: All laparoscopic adrenalectomies were finished successfully, and no open
      surgery was necessary. Major postoperative complications were not observed. Mean
      hospital stay was 3 days. No patient required blood transfusion. CONCLUSIONS:
      Laparoscopic adrenalectomy for functioning adrenal tumors proved a safe and
      minimally invasive procedure. Laparoscopic adrenalectomy, in comparison with open
      surgery, has numerous advantages, including a shorter length of stay, shorter
      time to return to preoperative level of activity, better cosmetic effect, and
      decrease in postoperative pain.

PMID- 17212204
TI  - [Clinical characteristics of patients with renovascular hypertension].
AB  - The aim of our study was to show the value of comparing clinical parameters in
      patients with renovascular hypertension (RVH) and essential hypertension (EH). We
      examined the differences between renovascular hypertension patients with
      atherosclerosis (ATH) and those with fibromuscular dysplasia (FMD). The diagnosis
      of renovascular hypertension was established on the basis of renal angiography
      finding, which also defined the type of stenosis (ATH or FMD). Our patient group
      included 108 patients with atherosclerotic RVH (46 male / 62 female, median age
      53 yrs), 16 patients with FMD (3 male / 13 female, median age 49 yrs), and 106
      patients with EH (61 male / 45 female, median age 38 yrs). In comparison with
      patients with EH, patients with atherosclerotic RVH were found to be more
      frequently of female gender with lower body weight and height, older, and more
      frequently on therapy with antihypertensives. Their hypertension was of later
      onset and more severe stage. All those differences were statistically significant
      (P < 0.05). When analysis by genders was performed, women were more frequently
      smokers and had higher serum cholesterol levels, which is an explanation for
      higher proportion of female gender in atherosclerotic RVH patients. In patients
      with fibromuscular dysplasia a higher proportion of female gender was also
      present, but in comparison with ATH patients their hypertension was more often of
      a less than 5 years duration and they had lower serum creatinine and triglyceride
      levels. Our results are in agreement with the results of other authors who showed
      clinical parameters to be useful in screening of patients for further diagnostic
      procedure. This stresses the importance of good history, physical examination and
      well-chosen laboratory tests. They can't clearly establish or exclude the
      diagnosis of renovascular hypertension, but this approach could more easily point
      out those hypertensive patients who require a thorough work-up. Clinical
      parameters could furthermore help in determining the type of treatment of RVH.

PMID- 17212205
TI  - [Influence of visceral obesity on blood pressure values in patients with
      essential hypertension].
AB  - Obesity significantly increases the risk for the occurrence of cardiovascular
      disease in patients with essential hypertension. The aim of the study was to
      assess the frequency of obesity, measured by different methods, in patients with
      essential hypertension, its effect on arterial pressure, and to determine the
      best correlation between indicators of obesity and arterial pressure. The study
      included 88 patients with essential hypertension, 32 males, mean age 59.4 (+/-
      10.4) years, and 56 females, mean age 62.9 (+/- 8.8) years. Body weight (BW) and
      height (BH), waist circumference (WC), and body mass index (BMI) were measured
      for each subject. Arterial pressure was determined using mercury
      sphygmomanometer. Overweight patients were defined as those with BMI 25-29.9
      kg/m2, while obese as those with > or = 30 kg/m2. Abdominal obesity was assessed
      by WC. WC values exceeding 102 cm for men and 88 cm for women indicated obesity.
      Body measures of male patients were higher than those for women (BW 92.5 (+/-
      14.5) vs 76.7 (+/- 11.5) p < 0.001; BH 175.4 (+/- 7.4) vs 163.4 (+/- 5.8) p <
      0.001), significantly higher waist circumference values (102.4 (+/- 12.2) vs 94.1
      (+/- 13.9) p = 0.006), with no differences in age, BMI, and arterial pressure
      values (p > 0.05). Also, no differences were observed in the number of
      uncontrolled hypertensive patients or number of overweight or obese patients (p >
      0.05). The number of obese patients did not differ significantly with regard to
      the various measurement methods employed (BMI: M 50%, F 37%; waist measurement: M
      51%, F 54%). A significant difference was noted in arterial pressure values only
      in the male patient group on comparing patients with normal BW and obese patients
      (systolic blood pressure (SBP) 156 (+/- 22.5) vs 142 (+/- 6.4) p = 0.04;
      diastolic blood pressure (DBP) 94 (+/- 11.6) vs 82.5 (+/- 6.4) p = 0.05). The
      correlation between obesity indicators and arterial pressure was significant for
      WC only in the male group (SBP r = 0.33, DBP r = 0.35, p < 0.05). The frequency
      of obesity does not differ with regard to the determined obesity indicators.
      Obese men have higher risk for increased arterial pressure values. WC values
      correlate better with arterial pressure values as it is a more accurate indicator
      of abdominal obesity.

PMID- 17212206
TI  - [The role of endothelium in hypertension and atherosclerosis].
AB  - Endothelium was "discovered" as a separate organ in the last decades of the
      previous century. For a long time endothelial cells were considered as a very
      passive monolayer of cells just covering the inner part of vascular walls. The
      role of these cells was thought to be only a mechanical barrier between
      circulating blood and vascular structures. Nowadays, after a series of
      biochemical and experimental studies, one can name endothelium as an organ,
      covering approximately 700 sqaure meters, weighing about 1.5 kilos in an average
      male with weight of 70 kg. Not only its quantity, but also its function is
      amazing. The most prominent and first well studied function of endothelial cells
      is vasodilatation and vasoconstriction. Normal cells, which are intact and in
      function produce regularly one of the most important protecting agent in
      circulation: NO. Normal endothelial cells produce NO as a result of higher blood
      pressure or growing demand for oxygen. It is produced from aminoacid L-arginine
      as a result of enzyme activity: endothelial NO synthetase (eNOS). Interleukins
      also can increase production of NO. NO has also antiinflammatory efects, helping
      in reparation and healing processes. Prostacyclins are the second most important
      vasodilating agent produced in endothelium. On the other hand, vasoconstriction
      is also mediated via endothelium. Endothelin 1, angiotensin II and thromboxan A
      are produced in vascular wall by endothelial cells, acting as opponent to NO. ACE
      system is very active inside those cells, with permanent local angiotensin II
      formation, that mostly act on vascular wall itself. Effects of such generated
      angiotensin II stimulate activation of VCAM molecules, starting adhesion of
      monocytes, their penetration in vascular wall and activation. Acivated
      macrophages get in contact with oxidized LDL particles already inside the
      vascular wall, producing foam cells. That is the very begining of
      atherosclerosis. All negative effects of excess of angiotensin II should be
      reduced by effective therapy with ACE inhibitors or AT antagonists. Today it
      seems more important to act on excess in endothelial AII in order to regulate not
      only blood pressure, but long-term devastating effects on target organs,
      preventing atherosclerosis.

PMID- 17212207
TI  - [Arterial blood pressure measurement with mercury sphygmomanometer--more than a
      technique].
AB  - Arterial blood pressure has been measured using mercury sphygmomanometer and
      auscultatory method for more than a hundred years. The results obtained by this
      measurement method make the basis of almost all conclusions related to
      pathogenesis, epidemiology and treatment of arterial hypertension. However, some
      deviations from ordinarily obtained data have been observed but are undoubtedly
      due to superficial approach to this simple method. A number of lesser faults can
      together result in an eventually inaccurate conclusion both regarding diagnosis
      and assessment of therapeutic effects. The aim of this short review article is to
      remind us of those little efforts needed to be done for improving the exactness
      of measurement in order to increase the accuracy of results. The ultimate
      consequence should be better care of patients with high blood pressure.

PMID- 17212208
TI  - [The 1st International Symposium on Hypertension in Osijek. From laboratory bench
      to clinical settings].

PMID- 17212209
TI  - [Ultrapure dialysate: fiction or reality?].

PMID- 17212210
TI  - [Hypertension in pregnancy--guidelines of European Society of Hypertension].

PMID- 17212211
TI  - [Recent studies on prevention of cerebrovascular incidents in hypertensive
      patients].

PMID- 17212212
TI  - [What looks like a kidney, isn't always a kidney].

PMID- 17212213
TI  - Betting big on doc ownership. 'Boutique' chain blasts off with $1 billion
      investment, plans for 10 hospitals, and hopes to create healthcare model of the
      future.
AB  - A new "boutique" chain is roaring out the gate with $1 billion to spend and plans
      for 10 hospitals. University General Hospital Systems, which aspires to offer the
      feel of a luxury hotel in its facilities, is wading into the thick of some of the
      most controversial issues in healthcare. All but one of its hospitals are planned
      for states without CON laws, according to W.J. "Bill" Burk, left.

PMID- 17212214
TI  - 'Stealth' chains lure big bucks.

PMID- 17212215
TI  - Employers drive personal records. Large firms unveil system that gives consumers
      control.

PMID- 17212216
TI  - Cashing in on technology. Vanderbilt, others go out of house with health IT.

PMID- 17212217
TI  - Measuring community benefits. Report finds tax-exempts edge out for-profits on
      giving.

PMID- 17212218
TI  - JCAHO floats IT to propel safety. Accreditor wants hospitals to embrace
      technology.

PMID- 17212219
TI  - La. judge mulls motion on HMO. Oath's defense wants case ended, says no crime
      alleged.

PMID- 17212220
TI  - Deal or no deal? Major for-profits buy and decide; one closes hospital.

PMID- 17212221
TI  - D.C. hospital plan up in smoke. Tobacco-settlement funds to go to other health
      areas.

PMID- 17212222
TI  - Hospitals' predicament. Will better patient care come from competition or
      regulation?

PMID- 17212223
TI  - Modern Healthcare 2006 Spirit of Excellence awards.

PMID- 17212224
TI  - Sugar rush. Makers of continuous-monitoring devices for diabetics target
      hospitals.

PMID- 17212225
TI  - Leaving troubles behind. Hospital with colorful past seeks bright future.

PMID- 17212226
TI  - The portrait of Dr William Harvey in the Royal Society since 1683.
AB  - A portrait of William Harvey in the Royal Society since 1683 is a copy by an
      unknown artist after a portrait, now lost, painted by Sir Peter Lely ca. 1650.
      Three other unattributed copies besides a copy bought from Lely's studio on his
      death by the Earl of Bradford have been located. The present labelling of the
      Royal Society portrait should be corrected.

PMID- 17212227
TI  - Standardization of biological medicines: the first hundred years, 1900-2000.
AB  - The use of materials of biological origin in medicine has a long history. These
      materials, including tissue, organ and microbial extracts, blood and its
      derivatives, antibodies and hormones, share the feature that for much of the last
      century the ability to characterize and quantify the active substance was
      limited. Quantification of these substances depends on biological
      standardization, a discipline that was refined to a science by the Medical
      Research Council from the 1920s onwards, and which, with contributions from
      several prominent Fellows of the Royal Society, including principally Sir Henry
      Dale, the UK has led the world to the present date.

PMID- 17212229
TI  - Medical encounter concepts and practices in India: a historical outline.

PMID- 17212228
TI  - [Foreign knowledge being tested: European physicians fighting the Moscow plague
      of 1771].
AB  - The transfer of Western medicine to Russia increased significantly in the
      Eighteenth century. Foreign doctors were employed, their writings translated,
      their education standards copied. But who regarded that knowledge as superior and
      why? Taking the Moscow Plague of 1771 as a case study, this article examines the
      crucial role foreign and Russian medical practitioners played during the
      epidemic. It argues that especially those ideas and practices that were useful
      for social control filtered into politics and public discourse, but failed to
      convince the majority of the population.

PMID- 17212230
TI  - Congress: over and out. Just before the session ended, Congress approved
      legislation that could lead to a 7.5% Medicare reimbursement cut in '08.
AB  - The 109th Congress spent its final minutes ramming through some major healthcare
      provisions, including one that could lead to a 7.5% cut in Medicare pay to
      physicians in 2008. The AMA is ready to work with lawmakers to fix the flawed
      physician payment formula, says AMA Chairman Cecil Wilson, left.

PMID- 17212231
TI  - Doubts cast on preparedness. AHA says such reports use worst-case scenarios.

PMID- 17212232
TI  - IHI's ambition rises for '07. Group aims to spare 5 million from harm in
      campaign.

PMID- 17212233
TI  - Boosting personal records. Blues, AHIP offer model health record for patient use.

PMID- 17212234
TI  - Straining family budgets. 19% of U.S. pays over 10% of income for care: study.

PMID- 17212235
TI  - SEIU hits Sutter in wallet. California delays $958 million bond application.

PMID- 17212236
TI  - Not-for-profit anxiety. Illinois bill may deny tax exemptions.

PMID- 17212237
TI  - A holiday wish. Instead of more goodies, healthcare needs an outside panel to
      study solutions.

PMID- 17212238
TI  - The underachieving has to stop. It's time for the U.S. healthcare system to be
      world-class for all of its patients.

PMID- 17212239
TI  - Looking back on 2006.

PMID- 17212240
TI  - Making it official. Indian Health Service, Mayo enter partnership to aid Native
      populations.

PMID- 17212241
TI  - 'Piper' plays same tune, different venue. After leading the charge at the VA,
      Perlin takes his passion for safety to HCA.

PMID- 17212242
TI  - ["Wait-and-see" in acute otitis media. An effective method for antibiotics use
      reduction--but a follow up is necessary].

PMID- 17212243
TI  - [The wolf is coming...or not. Mass medial journalism seeks sensations--news
      scooping makes a holistic view more difficult, and source investigation suffers].

PMID- 17212244
TI  - [Substantial blood glucose control differences at Swedish surgery departments.
      Common guidelines required].

PMID- 17212245
TI  - [Cryoablation in atrial fibrillation--safe and painless treatment. Experiences
      from the coronary unit at the Karolinska University Hospital].

PMID- 17212247
TI  - [Y chromosome--a sensitive resource or an evolutionary dead end?].

PMID- 17212246
TI  - [Practically no evidence for antibiotic treatment of chronic prostatitis].

PMID- 17212248
TI  - [Vocal cord dysfunction--differential diagnosis of asthma. Symptoms description
      and treatment suggestions].

PMID- 17212249
TI  - [Interaction between Trombyl and ACE inhibitor].

PMID- 17212250
TI  - [Silence of the Lambs].

PMID- 17212251
TI  - [Sodium deficiency caused by Seltin and drugs].

PMID- 17212252
TI  - [Conditional outpatient care is necessary until psychiatric services have been
      restored].

PMID- 17212253
TI  - [Homocysteine seldom reduced by pyridoxine!].

PMID- 17212254
TI  - [Coercion always necessary in psychiatry].

PMID- 17212255
TI  - ["Terminal care" instead of "self determination"].

PMID- 17212256
TI  - [Luciano was able to live and die at home].

PMID- 17212257
TI  - [Pro and contra case remuneration reform].

PMID- 17212258
TI  - [Trusting relationships as the "antidote"].

PMID- 17212259
TI  - [Liberating handicapped children from isolation].

PMID- 17212260
TI  - [A different kind of nursing care routine].

PMID- 17212261
TI  - [Cat tears].

PMID- 17212262
TI  - ["Geriatric nursing should be the coronation of nursing care" (interview by Urs
      Luthi)] (interview)].

PMID- 17212263
TI  - [Conflicts with uncomfortable dynamics].

PMID- 17212264
TI  - [World deficit of nurses].

PMID- 17212265
TI  - [A page turns].

PMID- 17212266
TI  - [Medical care in catastrophies].

PMID- 17212267
TI  - [A convivial repast].

PMID- 17212269
TI  - [Valuable drug for women in poor countries scraped--why?].

PMID- 17212270
TI  - [About mice and men. Not certain that findings in mice with Alzheimer disease can
      be applied in clinical reality].

PMID- 17212271
TI  - [The Patient Injury Committee secures the Patient Injury Act application. The
      goal is a just and a unified practice].

PMID- 17212272
TI  - [Multiresistant bacteria bigger and bigger threat in Swedish ICU. Quality
      assurance of hygiene routines and registration of complications are needed].

PMID- 17212274
TI  - [Urinary incontinence care program didn't achieve its goal. Referrals increased
      and investigations are still performed at levels too high].

PMID- 17212273
TI  - [Big regional differences when it comes to the number of performed coronary
      interventions. Different clinical practice...or greater risk of heart disease in
      certain parts of the country?].

PMID- 17212275
TI  - [Effective management of suspected skin cancer. New logistics introduced in
      Helsingborg].

PMID- 17212276
TI  - [Codeine and breast feeding].

PMID- 17212277
TI  - [The chairman is concealing facts about physician scheduling in big hospitals].

PMID- 17212279
TI  - [Grades superfluous in medical education)].

PMID- 17212278
TI  - [Introduce grades in medical education!].

PMID- 17212280
TI  - [Europe agrees to take the narrow road].

PMID- 17212281
TI  - [Can a week-long cortisone treatment for ulcerative colitis really reduce the
      risk of colectomy?].

PMID- 17212282
TI  - [Prenatal diagnosis and ethics--one more time].

PMID- 17212284
TI  - Getting our message across.

PMID- 17212285
TI  - Tribunals and tribulations.

PMID- 17212286
TI  - College faces cash queries.

PMID- 17212287
TI  - "Transferable skills are worthless if no new posts are created".

PMID- 17212288
TI  - 'I would rather have a few minutes with my baby alive than nothing at all'.

PMID- 17212289
TI  - We should balance patients' wishes with treatment needs.

PMID- 17212290
TI  - Driving reform. Interview by Richard Staines.

PMID- 17212291
TI  - Combating high cholesterol. Interview by Ann Shuttleworth.

PMID- 17212292
TI  - New clinical guidance to support patients with dementia.
AB  - NICE and the Social Care Institute for Excellence have issued guidance to help
      health and social care professionals support the 750,000 people in the UK who
      have dementia and their carers. The guidance addresses the full range of
      treatments and services for people. This article outlines how professionals can
      work to ensure the recommendations are successfully implemented.

PMID- 17212293
TI  - Muscle physiology--part 4: movement and muscle problems.

PMID- 17212294
TI  - Nurses' role in nutritional assessment and screening (second of a two-part
      series).
AB  - Nutrition is a key issue for healthcare professionals yet the management of
      nutritional problems by staff is often poor. Malnutrition is recognised as a
      significant risk for patients in hospital, a risk that nurses have a
      responsibility to monitor. The first article in this two-part series looked at
      initial assessment. This article looks at more specific tests that can be used to
      identify those at risk.

PMID- 17212295
TI  - A nurse-led gynaecology emergency assessment service.
AB  - A gynaecology emergency assessment unit was established because an increasing
      number of women were being referred to the gynaecology ward for assessment. On
      average 180 women a month are assessed at the unit and there is potential for
      that number to increase. An audit has revealed that only 7.2% of women seen in
      the unit required admission, the remainder being suitable for treatment as
      outpatients. Before the unit was established it was normal practice for any
      referrals to be automatically admitted until the junior doctor on call could
      assess them and decide an appropriate care plan.

PMID- 17212296
TI  - How to search for and use 'grey literature' in research.
AB  - An ever-growing amount of grey literature is available to nurses, including oral
      presentations, personal communication, leaflets, newspapers and magazines,
      unpublished research, internal reports and minutes of meetings. It can be an
      invaluable research resource.

PMID- 17212297
TI  - [On dealing with medical malpractice].

PMID- 17212298
TI  - [Prevalence and role of psychiatric disorders in disability].
AB  - Common risk factors for the receipt of disability income (DI) are psychiatric
      diagnosis at the time of conscription, showing low personal responsibility and
      job satisfication, unemployment after graduation, low rating on an "IQ" test, low
      educational level, part-time employment, isolation, separation, smoking, problem
      drinking, poor subjective state of health and well-being. Psychiatric diagnoses
      are considered to be the main reason for disability income in women and rank
      third in men. With average retirement age of 39 for males and 42 for females,
      schizophrenia is the most important single reason for early retirement before age
      40. Major depression has been shown to be the fourth leading cause of DI
      worldwide. Personality disorders, which display primarily antisocial, histrionic,
      emotionally unstable and narcissistic behaviour (Cluster B personality disorders)
      have been associated with an earlier age of work disability, and borderline
      personality has been associated with failure to return to work. A dependent,
      schizoid, paranoid and antisocial personality tends to be associated with an
      increased risk of developing disability. A subtype of adaptation disorder that is
      characterised primarily by lasting embitterment after exceptional life events,
      which violate basic beliefs, namely post-traumatic embitterment disorder, shows
      up highly the development of DI. However, most of the patients applying for a DI
      have neither been sufficiently diagnosed nor received adequate psychiatric and/or
      psychotherapeutic treatment when they claim on their DI policy. Thus, the
      prognosis of the diseases listed above could well be improved at least for some
      patients depending on their disease (10-80 %).

PMID- 17212299
TI  - [Rehabilitation and integration management].
AB  - At the core of a high-quality and efficient rehabilitation management, there is
      always a sophisticated analysis of each specific case and situation. This
      analysis is performed from a professional, medical and psychological point of
      view. It is set in the context of a case situation with regard to elements of
      civil law and social security regulations. The analysis explicitly takes the
      overall situation of the client into account. The success of the rehabilitation
      plan - and the amount of the overall costs--depend very much on the level of
      accuracy with which this analysis is conducted. Highly competent medical and job
      specific knowledge, as well as psychological know-how, is required.
      Rehabilitation management does not refer to a fixed set of certain measures, but
      has to be applied to the specific healing plan and resources of the client.

PMID- 17212301
TI  - ["For the welfare of patients"--is this really the case?].
AB  - According to a decision by the German Federal Constitution Court (1 BvR 347/98),
      it is illegal to refuse compulsorily insured persons therapy if they suffering
      from a lifethreatening disease against which there is no effective therapy on the
      basis of current medical science. The chosen method of treatment should offer a
      not entirely remote chance of healing. What counts is the effect treatment has in
      each individual case. Serious objections to the the Court's criteria have been
      expressed by medical and legal experts, who contend that the Court has
      disregarded patients' protection against unknown risks and "quackery" as well as
      the incalculable financial effects on the community of insureds.

PMID- 17212300
TI  - [Return-to-work-therapy in mentally ill employees: experiences with case
      management activities by private health insurers].
AB  - The development of a "return-to-work-therapy" [RTW-therapy] is described. It was
      initiated about 3 years ago by case-management teams of private health insurers
      in Germany to bridge the traditional gap between cure and rehabilitation of
      mainly depressive employees. The RTW-therapy aims at best-supported recovery of
      working capacity in patients after partial improvement of their depression. RWT
      therapy is a mixture of curative and rehabilitative medicine and incorporates new
      aspects of case management, i.e. coaching. RWT-therapy tries to overcome
      (minimise) the depression-induced impairment of working activity mainly by
      supporting the patients empowerment to start working without a complete recovery
      of depressive symptoms. The rationale is that a supported recovery to work
      enhances the positive coping experiences of the patient, which hopefully leads to
      a further improvement of depressive symptoms. About 24.6 % of the patients
      managed to start working again after about 16 weeks of RTW-therapy following a
      continuous sick leave duration of about 63 weeks.

PMID- 17212302
TI  - [Health care reform 2006: the way in state-controlled medicine].

PMID- 17212303
TI  - [Perturbative field therapy in neural therapy--scientifically neither proven nor
      accepted].

PMID- 17212304
TI  - [The genetic code of viral influenza--what does it say to us today, how can it be
      of use in the future?].

PMID- 17212305
TI  - [The first approved biotech-generic].

PMID- 17212306
TI  - [Above elbow amputation due to acupuncture treatment?].

PMID- 17212307
TI  - [CME-ECG 15].

PMID- 17212309
TI  - [Research interest by general practitioners: a survey].
AB  - BACKGROUND: For doing research on topics in primary care medicine participation
      of primary care physicians is necessary. Research in this field of medicine is
      only marginally established in Switzerland. OBJECTIVE: In a postal survey we
      evaluate the general attitudes of physicians towards research in the field of
      primary care. In particular we were interested in their willingness to
      participate in research projects and the facilitating and impeding factors to
      take part in such projects. METHODS: A purpose designed questionnaire was sent by
      post to 3044 primary care physicians in the central and eastern parts of
      Switzerland. RESULTS: The return rate was 52%. A majority of 94% of the
      responding physicians revealed interest in primary care research and 60% of all
      responders are willing to participate actively in such projects. They are
      prepared to spend about 15 min a day for data acquisition. Their willingness to
      participate depends on the conditions that, first, the research topic is relevant
      for daily practice and, second, boards odder Continuous Medical Education credits
      for time spent for research. Time constraints, additional administrative work and
      lack of relevance of research topics to daily practice are the main barriers.
      CONCLUSION: This survey demonstrates the general interest of primary care
      physicians to participate in relevant research projects. Therefore the structure
      to set up such research should be established.

PMID- 17212308
TI  - [What is your diagnosis? Episcleritis. Observing the disease course].

PMID- 17212310
TI  - [MRI-based diagnosis of giant cell arteritis].
AB  - The giant cell arteritis and its symptoms are usually non-specific and
      accompanied with symptoms of polymyalgia rheumatica. As complications of the
      giant cell arteritis ischemia, infarction or rupture of the damaged vessel can
      occur. We report on a 56-year-old female patient, who suffered for one year about
      weight loss, tiredness and intolerance as well as symptoms of polymyalgia
      rheumatica. Gastroscopy and colonoscopy showed normal findings. In the context of
      the malignancy search we made a computer tomography and magnet resonance
      tomography. The data showed an enlargement and an enhancement of the aorta, which
      led us to the suspicion of a giant cell arteritis. We started immediately with a
      medical treatment. The biopsy of the arteries temporales supported histological
      the diagnosis.

PMID- 17212311
TI  - [Simultaneous defect of visual fields and loss of libido--a coincidence?].
AB  - We present the case of a 60 year old male patient with incidentally detected
      visual abnormalities. Detailed personal history revealed a hypogonadism that had
      been present for several years. Further investigations established the diagnosis
      of an infiltrative macroadenoma. Medical treatment with cabergoline led to a
      rapid regression of ophthalmologic symptoms and, subsequently, of tumor size. In
      male subjects symptoms of hypogonadism are often reported only late in the course
      of the disease, thereby leading to a generally larger tumor size at the point of
      diagnosis. In contrast to other pituitary tumors that are mainly treated by
      surgery, medical treatment with dopamine agonists is the principal therapeutic
      option in prolactinomas.

PMID- 17212312
TI  - [36 year-old patient with multiple hypodense splenic lesions].

PMID- 17212313
TI  - [CME ultrasound diagnosis 14. Palpable nodes in the neck. Hashimoto thyroiditis
      with papillary thyroid carcinoma and multiple lymph node metastases in the neck].

PMID- 17212315
TI  - [The Medical Products Agency's new guidelines for primary prevention of
      cardiovascular diseases. No help to physicians].

PMID- 17212314
TI  - [Time for better organization of brain injury rehabilitation!].

PMID- 17212316
TI  - [High class of Swedish health economics seen from the international point of
      view. Continuous progress demands economical and political support according to
      an evaluation].

PMID- 17212317
TI  - [Sensory innervation of the back incorrectly described in dermatomal maps].

PMID- 17212318
TI  - [Evidence for low-dosage prednisolone in early rheumatoid arthritis. Prevents
      destruction of the joints and relieves symptoms].

PMID- 17212319
TI  - [Exercise and self confidence--keys to better mental health of the elderly].

PMID- 17212320
TI  - [Thalassemia in Sweden. Considerably varying therapeutic targets and follow up
      routines].

PMID- 17212321
TI  - [Guidelines of the Pharmaceutical Benefits Board for health economics
      evaluations. Cost-efficiency analysis from a national perspective].

PMID- 17212322
TI  - ["Blowing"...or...parent's kiss. A careful method for removal of nasal foreign
      bodies].

PMID- 17212323
TI  - [NSAID and fracture healing].

PMID- 17212324
TI  - [Reply concerning the new Medical Products Agency's guidelines for primary
      prevention of cardiovascular diseases. Issuing recommendations based on available
      evidence basis an ethical duty].

PMID- 17212325
TI  - [Y-BOCS might contribute to discrimination in health care because of sexual
      orientation].

PMID- 17212326
TI  - [Diabetes and myocardial infarction: intensive glucose control important
      according to international guidelines].

PMID- 17212327
TI  - [Crazy directives reduce productivity in health care!].

PMID- 17212329
TI  - If you're also teaching.

PMID- 17212328
TI  - [Tribonate infusion in lactic acidosis can be life-saving].

PMID- 17212330
TI  - Try online data backup.

PMID- 17212332
TI  - Communication tips: helping specialists help you.

PMID- 17212331
TI  - Calming the angry patient.

PMID- 17212333
TI  - Get your NPI asap!

PMID- 17212334
TI  - What's a micropractice?

PMID- 17212335
TI  - Stop taking new patients? Think twice.

PMID- 17212336
TI  - Is your practice fulfilling?

PMID- 17212337
TI  - What would you do? Testing and insurance.

PMID- 17212338
TI  - Doc on the box.

PMID- 17212339
TI  - Malpractice. 3 lessons I learned the hard way.

PMID- 17212341
TI  - 1H NMR metabonomics of plasma lipoprotein subclasses: elucidation of metabolic
      clustering by self-organising maps.
AB  - (1)H NMR spectra of plasma are known to provide specific information on
      lipoprotein subclasses in the form of complex overlapping resonances. A
      combination of (1)H NMR and self-organising map (SOM) analysis was applied to
      investigate if automated characterisation of subclass-related metabolic
      interactions can be achieved. To reliably assess the intrinsic capability of (1)H
      NMR for resolving lipoprotein subclass profiles, sum spectra representing the
      pure lipoprotein subclass part of actual plasma were simulated with the aid of
      experimentally derived model signals for 11 distinct lipoprotein subclasses. Two
      biochemically characteristic categories of spectra, representing normolipidaemic
      and metabolic syndrome status, were generated with corresponding lipoprotein
      subclass profiles. A set of spectra representing a metabolic pathway between the
      two categories was also generated. The SOM analysis, based solely on the
      aliphatic resonances of these simulated spectra, clearly revealed the lipoprotein
      subclass profiles and their changes. Comparable SOM analysis in a group of 69
      experimental (1)H NMR spectra of serum samples, which according to biochemical
      analyses represented a wide range of lipoprotein lipid concentrations,
      corroborated the findings based on the simulated data. Interestingly, the choline
      N(CH(3))(3) region seems to provide more resolved clustering of lipoprotein
      subclasses in the SOM analyses than the methyl-CH(3) region commonly used for
      subclass quantification. The results illustrate the inherent suitability of (1)H
      NMR metabonomics for automated studies of lipoprotein subclass-related metabolism
      and demonstrate the power of SOM analysis in an extensive and representative case
      of (1)H NMR metabonomics.

PMID- 17212342
TI  - A mouse model of basal-like breast carcinoma with metaplastic elements.
AB  - Breast cancers arising in carriers of germline BRCA1 mutations frequently have a
      basal-like phenotype. Basal-like cancers are characterized by high histological
      grade, central necrotic areas, foci with metaplastic differentiation, lack of
      hormone receptor and HER2 (ErbB2) expression, and consistent positivity for basal
      markers, including CK5/6, CK14, and EGFR. We have used germline manipulation to
      generate a conditional mouse model of Brca1 deficiency. Transgenic expression of
      Cre recombinase in the mammary gland of these mice results in deletion of exons
      encoding the C-terminus of Brca1 and leads to tumour formation when combined with
      heterozygosity for a p53 mutation. Histologically, these mammary gland tumours
      were characterized by high histological grade, central necrotic areas, and
      presence of homologous metaplastic elements. These metaplastic elements consisted
      of neoplastic spindle cells or squamous cell differentiation in the form of
      keratin pearls or individual cell keratinization. Immunohistochemical analysis
      revealed expression of basal-like markers in all cases. The tumour phenotype
      generated in our mouse model was compared with published data on human basal-like
      breast carcinomas and also with metaplastic breast cancers with a basal-like
      phenotype; the comparison showed that we have generated a mouse model of basal
      like breast cancer, which should prove useful in testing new and targeted
      treatments for this type of breast cancer.

PMID- 17212343
TI  - Importance of the liver in systemic complications associated with acute
      pancreatitis: the role of Kupffer cells.
AB  - Although its exact nature is still unknown, acute pancreatitis progresses with a
      local production of inflammatory mediators, eventually leading to systemic
      inflammatory response syndrome. Knowing that almost all pancreatic mediators
      released from the pancreas to the bloodstream may pass through the liver before
      their dilution in the systemic circulation, it would be reasonable to assume a
      determinant role for this organ in the development of the inflammatory response
      associated with acute pancreatitis. Thus, recent studies have shown the
      involvement of the liver in the complex network of events triggering the
      multiorgan dysfunction associated with the disease. Once pancreatic mediators
      reach the liver, they strongly activate Kupffer cells, the resident macrophages,
      greatly amplifying the release of cytokines into the bloodstream and thus
      contributing to the systemic manifestations of acute pancreatitis. Altogether,
      these results show that the pancreas is not the only source of mediators that
      trigger the deleterious effects of acute pancreatitis, but that the liver may
      orchestrate the final outcome of the disease. The purpose of this review is to
      discuss progress in understanding the function of the liver in the early stages
      of the development of systemic organ dysfunction secondary to acute pancreatitis.

PMID- 17212344
TI  - Cytochrome b gene sequence and structure of Pyrenophora teres and P. tritici
      repentis and implications for QoI resistance.
AB  - Resistance to QoI fungicides in Pyrenophora teres (Dreschsler) and P. tritici
      repentis (Died.) Dreschsler was detected in 2003 in France and in Sweden and
      Denmark respectively. Molecular analysis revealed the presence of the F129L
      mutation in resistant isolates of both pathogens. In 2004, the frequency of the
      F129L mutation in populations of both pathogens further increased. The G143A
      mutation was also detected in a few isolates of P. tritici-repentis from Denmark
      and Germany. In 2005, the F129L mutation in P. teres increased in frequency and
      geographical distribution in France and the UK but remained below 2% in Germany,
      Switzerland, Belgium and Ireland. In P. tritici-repentis, both mutations were
      found in a significant proportion of the isolates from Sweden, Denmark and
      Germany. The G143A mutation conferred a significantly higher level of resistance
      (higher EC50 values) to Qo inhibitors (QoIs) than did the F129L mutation. In
      greenhouse trials, resistant isolates with G143A were not well controlled on
      plants sprayed with recommended field rates, whereas satisfactory control of
      isolates with F129L was achieved. For the F129L mutation, three different single
      nucleotide polymorphisms (SNPs), TTA, TTG and CTC, can code for L (leucine) in P.
      teres, whereas only the CTC codon was detected in P. tritici-repentis isolates.
      In two out of 250 isolates of P. tritici-repentis from 2005, a mutation at
      position 137 (G137R) was detected at very low frequency. This mutation conferred
      similar resistance levels to F129L. The structure of the cytochrome b gene of P.
      tritici-repentis is significantly different from that of P. teres: an intron
      directly after amino acid position 143 was detected in P. teres which is not
      present in P. tritici-repentis. This gene structure suggests that resistance
      based on the G143A mutation may not occur in P. teres because it is lethal. No
      G143A isolates were found in any P. teres populations. Although different
      mutations may evolve in P. tritici-repentis, the G143A mutation will have the
      strongest impact on field performance of QoI fungicides.

PMID- 17212345
TI  - The effect of enzymatically degradable IPN coatings on peri-implant bone
      formation and implant fixation.
AB  - Short-term osseointegration of orthopedic implants is critical for the long-term
      stability of the implant-bone interface. To improve initial implant stability,
      one strategy under consideration involves the presentation of adhesion ligands on
      the implant surface to stimulate bone regeneration in the peri-implant region. To
      assess the relative effects of implant surface chemistry and topography on
      osseointegration within the rat femoral ablation implant model, a nonfouling,
      enzymatically degradable interpenetrating polymer network (edIPN) of poly(AAm-co
      EG/AAc) amenable to presenting the cell signaling domain Arg-Gly-Asp (RGD), was
      developed. Moderate enhancement of peri-implant bone formation was found after 28
      days using the edIPN without peptide modification (p = 0.032). However, no data
      supported a benefit of peptide modification, as bone-implant contact, normalized
      bone volume and normalized fixation strength was equivalent or poorer than dual
      acid-etched (DAE) treated implants after 28 days. Surface topography was
      determined to be the dominant factor in modulating osseointegration, as DAE
      implants produced equivalent roughness-normalized fixation strength versus
      previously reported data on plasma-sprayed hydroxyapatite/tricalcium phosphate
      coated implants (Barber et al., J Biomed Mater Res A, forthcoming). An ideal
      osseointegrated implant will require optimization of all three aforementioned
      parameters, and may take the form of biomolecule delivery from thin degradable
      polymer networks.

PMID- 17212346
TI  - Shape-engineered vascular endothelial cells: nitric oxide production, cell
      elasticity, and actin cytoskeletal features.
AB  - Single cell shape determines cellular functions. Therefore, control of cell shape
      is of considerable importance for the tissue engineering field. This study was
      designed to assess the effect of surface-induced shaping of vascular endothelial
      cells (ECs) on the intracellular nitric oxide (NO) production level, the cell
      elasticity, and cytoskeletal (CSK) features on shape-engineered ECs (round, 90,
      120 microm diameter; spindle-shaped, 20, 30, 40 microm width) prepared on a
      photolithographically microprocessed surface. Intracellular NO production was
      measured using a microscopic spectrometer with diaminofluorescein diacetate
      probe. Cell elasticity and actin CSK features were analyzed through
      microindentation measurement and fluorescence observations with fluorescence and
      atomic force microscopy. Results showed that spindle-shaped cells exhibited lower
      NO production, higher cell stiffness, and denser actin stress fibers than the
      round and nonrestrictedly cultured control cells. Relations between cell shape
      with NO production, cell elasticity, and actin CSK features were discussed.

PMID- 17212347
TI  - Effect of electrical stimulation pattern on the force responses of paralyzed
      human quadriceps muscles.
AB  - Most studies examining the effect of electrical stimulation pattern on the force
      response of muscle have been done in able-bodied persons. The purpose of this
      study was to examine the electrically elicited force responses of the paralyzed
      quadriceps femoris muscles of persons with spinal cord injuries (SCI) to see
      whether stimulation patterns that increase the force response in non-paralyzed
      muscle will do so in paralyzed muscle. Thirteen subjects ranging in age from 11
      to 24 years old with motor-complete SCI were studied. Isometric muscle
      performance was tested using 6-pulse constant-frequency trains (CFTs), variable
      frequency trains (VFTs), and doublet-frequency trains (DFTs) delivered at mean
      frequencies of 10, 20, 33, 50, and 100 HZ. In the non-fatigued and fatigued
      condition, the VFT and DFT peak forces were greater than the CFT peak forces at
      10 HZ. In addition, in the fatigued condition the 20-HZ VFT peak forces were
      greater than the CFT peak forces, and there was a trend for the DFT peak forces
      to be greater than the CFT peak forces. In the non-fatigued condition, the 33-HZ
      and 50-HZ DFT force-time integrals were greater than both the CFT and VFT force
      time integrals. In the fatigued condition, there was no significant effect of
      train-type on the force-time integrals. These results differ from those
      previously reported from studies using able-bodied persons and indicate that
      findings from studies of the electrically elicited force responses of the muscles
      of able-bodied persons do not apply to the paralyzed muscles of persons with SCI.

PMID- 17212348
TI  - Meralgia paresthetica caused by hip-huggers in a patient with aberrant course of
      the lateral femoral cutaneous nerve.
AB  - "Hip-huggers" may be a precipitating factor for meralgia paresthetica (MP),
      especially in thin persons with an aberrant pathway of the lateral femoral
      cutaneous nerve (LFCN). We describe a 25-year-old woman with a long-standing
      history of MP caused by an abnormal course of the LFCN and tight trousers,
      specifically hip-huggers. Ultrasonography was useful for detecting the lesion
      site and the abnormal pathway of the LFCN. After neurectomy of the LFCN, most of
      the symptoms of MP were relieved, but mild hypesthesia remained in the lateral
      thigh.

PMID- 17212349
TI  - Primary lateral sclerosis.
AB  - The spectrum of motor neuron diseases ranges from disorders that clinically are
      limited to lower motor neurons to those that exclusively affect upper motor
      neurons. Primary lateral sclerosis (PLS) is the designation for the syndrome of
      progressive upper motor neuron dysfunction when no other etiology is identified.
      Distinction between PLS and the more common amyotrophic lateral sclerosis (ALS)
      relies primarily on recognition of their symptoms and signs, as well as on
      ancillary, although non-specific, laboratory data. In this review, we survey the
      history of PLS from the initial descriptions to the present. We discuss the role
      of laboratory, electrodiagnostic, and imaging studies in excluding other
      diagnoses; the findings from major case series of PLS patients; and proposed
      diagnostic criteria. Consistent differences are evident in patients classified as
      PLS compared to those with ALS, indicating that, despite its limitations, this
      clinical designation retains important utility.

PMID- 17212350
TI  - A large German kindred with cold-aggravated myotonia and a heterozygous A1481D
      mutation in the SCN4A gene.
AB  - Muscle sodium-channel disorders cover a spectrum of rare myotonic diseases. In a
      German family with 17 affected individuals in four generations, we identified a
      heterozygous missense mutation in exon 24 A1481D (c.4442 C>A) of the voltage
      gated sodium channel gene (SCN4A) alpha subunit. Phenotypes of 12 family members
      were characterized by a mild myotonia with cold sensitivity but without
      paramyotonia. The index patient presented with fluctuating cold- and exercise
      induced stiffness of ocular, facial, and distal muscles. The myotonia became more
      severe at the age of 22 years. His father had had cold- and exercise-induced
      periodic weakness with fluctuating myotonia since age 10. Later he developed a
      more severe, purely exercise- and cold-aggravated myotonia of arms, hands, and
      facial muscles. The father's mother presented with cold-induced myotonia until
      age 65, when progressive weakness of proximal limb muscles developed. Her muscle
      biopsies revealed considerable myopathic changes with a variety of fine
      structural alterations. This study presents a family with cold-aggravated
      myotonia and progression of myopathic changes in the muscle biopsy with
      increasing age. In older patients, sodium channelopathies may mimic the
      phenotypic features of myotonic dystrophy type 2.

PMID- 17212351
TI  - Growth and mitogenic effects of arylphorin in vivo and in vitro.
AB  - In insects, developmental responses are organ- and tissue-specific. In previous
      studies of insect midgut cells in primary tissue cultures, growth-promoting and
      differentiation factors were identified from the growth media, hemolymph, and fat
      body. Recently, it was determined that the mitogenic effect of a Manduca sexta
      fat body extract on midgut stem cells of Heliothis virescens was due to the
      presence of monomeric alpha-arylphorin. Here we report that in primary midgut
      cell cultures, this same arylphorin stimulates stem cell proliferation in the
      lepidopterans M. sexta and Spodoptera littoralis, and in the beetle Leptinotarsa
      decemlineata. Studies using S. littoralis cells confirm that the mitogenic effect
      is due to free alpha-arylphorin subunits. In addition, feeding artificial diets
      containing arylphorin increased the growth rates of several insect species. When
      tested against continuous cell lines, including some with midgut and fat body
      origins, arylphorin had no effect; however, a cell line derived from Lymantria
      dispar fat body grew more rapidly in medium containing a chymotryptic digest of
      arylphorin.

PMID- 17212352
TI  - Biochemical mechanisms leading to tryptophan 2,3-dioxygenase activation.
AB  - Tryptophan 2,3-dioxygenase (TDO) is the first enzyme in the tryptophan oxidation
      pathway. It is a hemoprotein and its heme prosthetic group is present as a heme
      ferric (heme-Fe(3+)) form that is not active. To be able to oxidize tryptophan,
      the heme-Fe(3+) form of the enzyme must be reduced to a heme-ferrous (heme
      Fe(2+)) form and this study describes conditions that promote TDO activation. TDO
      is progressively activated upon mixing with tryptophan in a neutral buffer, which
      leads to an impression that tryptophan is responsible for TDO activation. Through
      extensive analysis of factors resulting in TDO activation during incubation with
      tryptophan, we conclude that tryptophan indirectly activates TDO through
      promoting the production of reactive oxygen species. This consideration is
      supported by the virtual elimination of the initial lag phase when either pre
      incubated tryptophan solution was used as the substrate or a low concentration of
      superoxide or hydrogen peroxide was incorporated into the freshly tryptophan and
      TDO mixture. However, accumulation of these reactive oxygen species also leads to
      the inactivation of TDO, so that both TDO activation and inactivation proceed
      with the specific outcome depending greatly on the concentrations of superoxide
      and hydrogen peroxide. As a consequence, the rate of TDO catalysis varies
      depending upon the proportion of the active to inactive forms of the enzyme,
      which is in a dynamic relationship in the reaction mixture. These data provide
      some insight towards elucidating the molecular regulation of TDO in vivo.

PMID- 17212353
TI  - Cloning and characterization of two cytochrome P450 CYP6AX1 and CYP6AY1 cDNAs
      from Nilaparvata lugens Stal (Homoptera: Delphacidae).
AB  - Two full-length P450 cDNAs, CYP6AX1 and CYP6AY1, were cloned from the brown
      planthopper Nilaparvata lugens Stal (Homoptera: Delphacidae). Both CYP6AX1 and
      CYP6AY1 are typical microsomal P450s and their deduced amino acid sequences share
      common characteristics with other members of the insect P450 CYP6 family. CYP6AX1
      and CYP6AY1 show the highest percent identity (36%) of amino acid to each other;
      both of them have 31-33% amino acid identity with CYP6B1 from Papilio polyxenes
      (Lepidoptera: Papilionidae), CYP6B4 from Papilio glaucus (Lepidoptera:
      Papilionidae), and CYP6B8 from Helicoverpa zea (Lepidoptera: Noctuidae).
      Phylogenetic analysis showed the clustering of CYP6AX1 and CYP6AY1 was in the
      clade including CYP6AE1 from Depressaria pastinacella (Lepidoptera: Oecophoridae)
      and the CYP6B family members from Helicoverpa and Papilio species. Northern blot
      analysis revealed that both of the P450s were induced by the resistant rice
      variety B5 (Oryza sativa L), and CYP6AY1 was expressed at a higher level than
      CYP6AX1. The results suggest that more than one P450s are likely involved in
      metabolism of rice allelochemicals and that they are possibly important
      components in adaptation of Nilaparvata lugens to host rice. Arch. Insect
      Biochem.

PMID- 17212354
TI  - Histone H1-like, lysine-rich low complexity amino acid extensions in mosquito
      ribosomal proteins RpL23a and RpS6 have evolved independently.
AB  - Histone H1-like amino acid extensions have been described at the amino terminus
      of Drosophila RpL22 and RpL23a, and at the carboxyl terminus of mosquito
      ribosomal protein RpS6. An in silico search suggested that RpL23a, but not RpL22,
      in Anopheles gambiae has an amino-terminal extension. Because low complexity
      amino acid extensions are not common on eukaryotic ribosomal proteins, and their
      functions are unknown, we cloned cDNAs encoding RpL23a from Aedes albopictus and
      Anopheles stephensi mosquito cell lines. RpL23a proteins in Aedes and Anopheles
      mosquitoes are rich in lysine (approximately 25%), alanine (approximately 21%),
      and proline (approximately 8%), have a mass of approximately 40 kDa, a pI of 11.4
      to 11.5, and contain an N-terminal extension of approximately 260 amino acid
      residues. The N-terminal extension in mosquito RpL23a is about 100 amino acids
      longer than that in the Drosophila RpL23a homolog, and contains several repeated
      amino acid motifs. Analysis of exon-intron organization in the An. gambiae and in
      D. melanogaster genes suggests that a short first exon encodes a series of 11
      amino acid residues conserved in RpL23a proteins from Drosophila, mosquitoes, and
      the moth, Bombyx mori. The histone H1-like sequence in RpL23a is encoded entirely
      within the second exon. The C-terminal 126 amino acid residues of the RpL23a
      protein, encoded by exon 3 in Drosophila, and by exons 3 and 4 in Anopheles
      gambiae, are well conserved, and correspond to Escherichia coli RpL23 with the
      addition of the eukaryotic N-terminal nuclear localization sequence. Sequence
      comparisons indicate that the histone H1-like extensions on mosquito RpS6 and
      RpL23a have evolved independently of each other, and of histone H1 proteins.

PMID- 17212355
TI  - Effect of the electrical currents generated by the intestinal smooth muscle
      layers on pancreatic enzyme activity: an in vitro study.
AB  - Gut enzymes in the small intestine are exposed to extremely low electrical
      currents (ELEC) generated by the smooth muscle. In the present study, the in
      vitro tests were undertaken to evaluate the effect of these electric currents on
      the activity of the proteolytic pancreatic digestive enzymes. A simulator
      generating the typical electrical activity of pig gut was used for these studies.
      The electric current emitted by the simulator was transmitted to the samples,
      containing enzyme and its substrate, using platinum plate electrodes. All samples
      were incubated at 37 degrees C for 1 h. The changes in optical density,
      corresponding to enzyme activity, in samples stimulated for 1 h with ELEC was
      compared with that not exposed to ELEC. The obtained results show that the
      electrical current with the characteristics of the myoelectrical migrating
      complex (MMC) has an influence on pancreatic enzyme activity. Increased
      endopeptidase and reduced exopeptidase activity was noticed in samples treated
      with ELEC. This observation can be of important as analyzed factors which can
      alter enzymatic activity of the gut, can thus also affect feed/food
      digestibility.

PMID- 17212356
TI  - Synergistic antiglioma activity of radiotherapy and enzastaurin.
AB  - OBJECTIVE: Radiotherapy is an essential treatment modality for malignant gliomas,
      but it exerts adverse effects via promotion of glioma cell invasion in
      experimental glioma. Furthermore, irradiation induces vascular endothelial growth
      factor (VEGF) levels in gliomas, which is associated with poor prognosis. Here,
      we investigate the combination of the protein kinase C-beta inhibitor enzastaurin
      (ENZA) and radiotherapy in vitro and in vivo in comparison with either treatment
      alone. METHODS: We analyzed the effects of ENZA and irradiation on migration,
      apoptosis, and proliferation of glioma cells, as well as VEGF secretion in vitro.
      Neurotoxicity of ENZA was assessed in cerebellar granule neurons. After
      orthotopic intracerebral implantation of LNT-229 glioma cells in nude mice, the
      effects of in situ cerebral irradiation and oral application of ENZA on survival,
      tumor size, VEGF expression, apoptosis, and microvessel density in vivo were
      analyzed. RESULTS: Combining cerebral irradiation with ENZA leads to longer
      survival in vivo. ENZA diminishes tumor volume, irradiation-induced tumor
      satellite formation, upregulation of VEGF expression in vitro and in vivo, as
      well as enhanced microvessel density in vivo. Importantly, ENZA is not neurotoxic
      in vitro or in vivo. INTERPRETATION: Long-term administration of ENZA after
      radiotherapy is feasible and leads to long-term survival without neurotoxicity.

PMID- 17212357
TI  - A real reason for patients with pseudobulbar affect to smile.
AB  - Pseudobulbar affect (PBA) is a dramatic disorder of emotional expression and
      regulation characterized by uncontrollable episodes of laughing and crying that
      often cause embarrassment, curtailment of social activities, and reduction in
      quality of life. The disorder occurs in patients with brain injury caused by many
      types of neurological disease, including stroke, tumors, and neurodegenerative
      gray and white matter disorders. Although the pathophysiology is unknown, PBA may
      relate to release of brainstem emotional control centers from regulation by the
      frontal lobes. Diagnosis of PBA can be difficult and relies on careful
      characterization of episodes and differentiation from depression. Although there
      are no US Food and Drug Administration-approved treatments for PBA, several
      agents have been shown to be effective, including tricyclic antidepressants,
      selective serotonin reuptake inhibitors, and a new agent containing
      dextromethorphan and quinidine. The growing number of treatment options, some of
      great benefit to patients, highlights the importance of accurate diagnosis of
      this disorder.

PMID- 17212358
TI  - VDR-mediated inhibition of DKK1 and SFRP2 suppresses adipogenic differentiation
      of murine bone marrow stromal cells.
AB  - Osteoblasts and adipocytes are thought to derive from a common bone marrow
      stromal cell (BMSC) precursor. Activation of the canonical Wnt signaling pathway
      plays a pivotal role in the differentiation of BMSCs along either of these two
      lineages, promoting osteogenesis and inhibiting adipogenesis. Liganded nuclear
      receptors, including the vitamin D receptor (VDR) and peroxisomal proliferator
      activated receptor gamma (PPARgamma), can also affect BMSCs differentiation. To
      address whether VDR ablation modulates the differentiation of BMSCs into the
      osteoblast or adipogenic lineages, BMSCs were isolated from VDR null mice and
      from their wild-type littermates. VDR ablation did not alter osteoblastic
      differentiation. However, when cultured under adipogenic conditions, BMSCs from
      the VDR null mice expressed higher mRNA levels of PPARgamma and of markers of
      adipogenic differentiation. An increase in the size and number of mature
      adipocyte foci was also observed in cultures isolated from VDR null mice relative
      to those isolated from wild-type mice. To address whether the increased
      adipogenesis observed in the VDR null cultures was associated with inhibition of
      the canonical Wnt signaling pathway, mRNA levels for DKK1 and SFRP2 were
      examined. Cultures from the VDR null mice expressed higher levels of mRNA
      encoding DKK1 and SFRP2 than did the wild-type cultures. This difference is, at
      least in part, due to ligand-dependent actions of the VDR, since 1,25
      dihydroxyvitamin D3 suppressed DKK1 and SFRP2 expression in wild-type cultures.
      Thus, the VDR inhibits adipogenesis of BMSCs at least in part by suppressing the
      expression of inhibitors of the canonical Wnt signaling pathway.

PMID- 17212359
TI  - Activation of ERK, JNK, Akt, and G-protein coupled signaling by hybrid
      angiotensin II AT1/bradykinin B2 receptors expressed in HEK-293 cells.
AB  - Bradykinin (BK) and angiotensin II (AngII) often have opposite roles in
      cardiovascular diseases. Our aim here was to construct hybrid receptors which
      bind AngII but signal as BK. Various sequences of the intracellular face of the
      AngII type I receptor, AT1R, were replaced with corresponding sequences from the
      bradykinin B2 receptor (BKB2R). The hybrids demonstrated a number of signaling
      characteristics of the BKB2R. For example, the hybrids demonstrated BK as opposed
      to AngII like phosphorylation of Akt and JNK. The hybrids containing the BKB2R
      intracellular loop 2 (IC2) displayed minimal G-protein, Galphai/Galphaq, linked
      signaling. Computer based molecular models suggested that Ser-Met-Gly from the
      IC2 of the BKB2R is detrimental for the Galphai/Galphaq coupled functions of this
      hybrid. The return of Lys-Ser-Arg of the AT1R to this hybrid led to almost full
      recovery of Galphai and Galphaq activation. The design and production of AT1/BKB2
      hybrid receptors is a potential approach in the treatment of hypertension related
      diseases where the presence of AngII, its AT1 receptor and the consequent signal
      transduction has proven detrimental.

PMID- 17212360
TI  - Protein kinase Calpha is differentially activated during neonatal and adult
      erythropoiesis and favors expression of a reporter gene under the control of the
      (A)gamma globin-promoter in cellular models of hemoglobin switching.
AB  - PKCalpha was found to be expressed (mRNA and protein) throughout the in vitro
      maturation of primary human erythroblasts but its activity (phosphorylation
      levels and nuclear localization) was consistently higher in cells derived from
      human neonatal rather than adult blood. Since the gamma/gamma + beta globin
      expression ratio represented the major difference between neonatal and adult
      erythroblasts (58 +/- 12 vs. 7 +/- 3, respectively), we tested the hypothesis
      that PKCalpha might affect gamma-globin expression by measuring the levels of
      (A)gamma- or beta-promoter-driven reporter activity in erythroid cells stably
      (GM979) or transiently (K562, primary adult and neonatal erythroblasts)
      transfected with a dual microLCRbetaprRluc(A)gammaprFluc reporter in the presence
      of transient expression of either the constitutively active (sPKCalpha) or
      catalytically inactive (iPKCalpha) PKCalpha. As further control, GM979 cells were
      incubated with the PKC inhibitor rottlerin (30 microM). In all the cells
      analyzed, sPKCalpha significantly increased (by two- to sixfold) the levels of
      luciferase activity driven by the (A)gamma-promoter and the (A)gamma-F/((A)gamma
      F + 2beta-R) expression ratio. In GM979 cells, rottlerin inhibited (by 50%) the
      (A)gamma-driven luciferase activity and the (A)gamma-F/((A)gamma-F + 2beta-R)
      expression ratio. These results suggest that different PKC isoforms may exert
      ontogenetic-specific functions in erythropoiesis and that modulation of PKCalpha
      might affect the activity of (A)gamma-promoter-driven reporters.

PMID- 17212361
TI  - Hyperglycemia and hyperinsulinemia have additive effects on activation and
      proliferation of pancreatic stellate cells: possible explanation of islet
      specific fibrosis in type 2 diabetes mellitus.
AB  - Pancreatic islet fibrosis observed in Type 2 diabetes is one of the major factors
      leading to progressive beta-cell loss and dysfunction. Despite its importance,
      the mechanism of islet-restricted fibrogenesis associated with pancreatic
      stellate cell (PSC) activation and proliferation remains to be defined.
      Therefore, we studied whether the islet-specific environment represented by
      hyperglycemia and hyperinsulinemia had additive effects on the activation and
      proliferation of cultured rat PSCs. Cells were stimulated to activate and
      proliferate with glucose and insulin, either individually or concomitantly. Both
      stimuli promoted PSC proliferation and extracellular signal-regulated kinase
      (ERK) 1/2 phosphorylation independently, but an additive effect was also
      demonstrated. Blockade of ERK signaling by the mitogen-activated protein kinase
      kinase (MEK) inhibitor, U0126, suppressed both glucose- and insulin-induced ERK
      1/2 phosphorylation and PSC proliferation. Glucose and insulin-induced ERK 1/2
      phosphorylation also stimulated connective tissue growth factor gene expression.
      Thus, hyperglycemia and hyperinsulinemia are two crucial mitogenic factors that
      activate and proliferate PSCs, and the presence of both states will amplify this
      response.

PMID- 17212363
TI  - Structural variation from 1D to 3D: effects of ligands and solvents on the
      construction of lead(II)-organic coordination polymers.
AB  - A series of Pb(II) coordination polymers [Pb(ndc)(dpp)] (1), [Pb(ndc)(ptcp)].0.5
      H2O (2), [Pb(ndc)(dppz)] (3), [Pb(ndc)(tcpn)(2)] (4), [Pb2(ndc)2(tcpp)] (5),
      [Pb(Hndc)2].H2O (6), [Pb(ndc)(dma)] (7), [Pb(bdc)(dma)] (8), [Pb(trans
      chdc)(H2O)] (9), and [Pb2(cis-chdc)2].NH(CH3)2 (10), where ndc=1,4
      naphthalenedicarboxylate, dpp=4,7-diphenyl-1,10-phenanthroline, ptcp=2-phenyl-1H
      1,3,7,8-tetraazacyclopenta[l]phenanthrene, dppz=dipyrido[3,2-a:2',3'-c]phenazine,
      tcpn=2-(1H-1,3,7,8-tetraazacyclopenta[l]phenanthren-2-yl)naphthol, tcpp=4-(1H
      1,3,7,8-tetraazacyclopenta[l]phenanthren-2-yl)phenol, dma=N,N-dimethylacetamide,
      bdc=1,4-benzenedicarboxylate, and chdc=1,4-cyclohexanedicarboxylate, have been
      synthesized from a hydrothermal or solvothermal reaction system by varying the
      ligands or the solvents. Compounds 1-5 crystallize with an N-donor chelating
      ligand and an aromatic dicarboxylate linker. Compounds 1-4 are 1D polymers with
      different pi-pi stacking interactions, whereas compound 5 consists of 2D layers.
      The structures of compounds 7, 8, and 10 are 3D frameworks formed by connection
      of the Pb(II) centers by organic acid ligands. Compound 7 is chiral although the
      ndc ligand is achiral, while the framework of 8 is a typical 3D (3,4)-connected
      net. Compound 10 is the first example of Pb(II) wheel cluster [Pb(8)O(8)] units
      bridged by carboxylate groups. Compound 6 contains 1D chains which are further
      extended to a 3D structure by pi-pi interactions. Compound 9 consists of a 2D
      network constructed by Pb(II) centers and trans-chdc ligands. The structural
      differences between 7 and 8 and between 9 and 10 indicate the importance of
      solvents for framework formation of the coordination polymers. By varying the
      solvent the cis and trans conformations of H(2)chdc in 9 and 10 were separated
      completely. The photoluminescence and nonlinear optical properties of the
      coordination polymers have also been investigated.

PMID- 17212362
TI  - Effect of hyperthermia on TRAIL-induced apoptotic death in human colon cancer
      cells: development of a novel strategy for regional therapy.
AB  - Approximately 25% of patients with colorectal cancer will develop metastatic
      disease exclusively or largely confined to the liver, and the vast majority of
      these cases are not amenable to surgical resection. These unresectable cases of
      liver metastatic disease can be treated with isolated hepatic perfusion (IHP),
      which involves a method of complete vascular isolation of the liver to allow
      treatment of liver tumors with toxic systemic doses of chemotherapeutic agents.
      To improve the efficacy of IHP, hyperthermia and biological agents have been
      applied along with the chemotherapeutic agents. In this study, we investigated
      whether hyperthermia in combination with tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) enhances mortality in human colorectal carcinoma CX-1
      cells. Cells were treated with various concentrations of TRAIL (0-200 ng/ml) at
      various temperatures (40-46 degrees C) for 1 h and further incubated at 37
      degrees C in the presence of TRAIL. We observed that hyperthermia at 42-43
      degrees C effectively promoted TRAIL-induced apoptosis, as indicated by cell
      death, poly (ADP-ribose) polymerase (PARP) cleavage, and activation of caspase-8,
      -9, and -3. In contrast, hyperthermia at 45-46 degrees C suppressed TRAIL-induced
      apoptosis. We also observed that mild hyperthermia, but not acute hyperthermia,
      promoted cytochrome c release during treatment with TRAIL. Our data suggest that
      promotion of cytochrome c release during mild hyperthermia is responsible for the
      enhancement of TRAIL cytotoxicity.

PMID- 17212364
TI  - Shape-controlled synthesis of 3D and 1D structures of CdS in a binary solution
      with L-cysteine's assistance.
AB  - A facile L-cysteine-assisted route was designed for the selectively controlled
      synthesis of 1D and novel, interesting 3D CdS spherical nanostructures
      constructed from CdS nanorods (or nanopolypods) in a binary solution. By
      controlling reaction conditions such as the molar ratio between Cd(OAc)2 and L
      cysteine and the volume ratio of the mixed solvents, the synthesis of various 3D
      architectural structures and 1D wirelike structures in large quantities can be
      controlled. This is the first reported case of the direct growth of novel 3D self
      assemblies of CdS nanorods (or nanopolypods). The morphology, structure, and
      phase composition of the as-prepared CdS products were examined by using various
      techniques (X-ray diffraction (XRD), field-emission scanning electron microscopy
      (FESEM), transmission electron microscopy (TEM), selected-area electron
      diffraction (SAED), high-resolution TEM, and Raman spectroscopy). On the basis of
      the results from TEM studies and our analysis, we speculate that in the present
      synthesis the L-cysteine dominates nucleation growth and the ethylenediamine (en)
      dominated, oriented-assembly process. Interestingly, the products obtained show a
      gradient evolution in color from light-yellow to dark-yellow, which implies that
      their intrinsic optical properties change, possibly due to variations in their
      special morphologies and structures. This facile solution-phase L-cysteine
      assisted method could be extended for the controlled preparation of other metal
      chalcogenides nanostructures with complex morphologies.

PMID- 17212365
TI  - C-O-bond cleavage of esters with a naphthyl group in the higher triplet excited
      state during two-color two-laser flash photolysis.
AB  - A C-O-bond cleavage of esters having a naphthyl group, NpCO-OR and RCO-ONp
      (Np=alpha- and beta-naphthyl ((alpha)Np and (beta)Np, respectively), R=Ph and
      Me), was found during the two-color two-laser flash photolysis in acetonitrile.
      The C-O-bond cleavage occurred when NpCO-OR and RCO-ONp were excited to the
      singlet excited states (S1). On the other hand, no reaction occurred from the
      lowest triplet excited states (T1). When NpCO-OR(T1) and RCO-ONp(T1) were excited
      to the higher triplet excited states (Tn) using the second laser during the two
      color two-laser flash photolysis, the C-O-bond cleavage occurred. The C-O-bond
      cleavage quantum yield (Phi) was estimated from the plots of the T1-state esters
      disappeared within a laser flash versus the second laser intensities. The C-O
      bond cleavage in (beta)NpCO-OPh(Tn) occurred more efficiently than in (alpha)NpCO
      OPh(Tn) and that in PhCO-O(beta)Np(Tn) occurred more efficiently than in PhCO
      O(alpha)Np(Tn). The Phi value for ester with Ph and beta-Np groups was larger
      than that for ester with Ph and alpha-Np groups. The Phi value for MeCO
      O(alpha)Np(Tn) was similar to those for PhCO-ONp(Tn), while that for MeCO
      O(beta)Np(Tn) was much smaller than those for PhCO-ONp(Tn) and MeCO
      O(alpha)Np(Tn). On the other hand, no C-O-bond cleavage was observed in NpCO
      OMe(Tn). The Phi value depended on the characters of the groups (Np, Ph, and Me)
      on the ester. Whether R is Ph or Me with or without pi electron, respectively, is
      important for the C-O-bond cleavage. In other words, electronic delocalization of
      the T(n) state including Np and ester groups is necessary for the occurrence of
      the C-O-bond cleavage in NpCO-OR(Tn) and RCO-ONp(Tn).

PMID- 17212366
TI  - Structures of the high-temperature solid phases of the odd-numbered fatty acids
      from tridecanoic acid to tricosanoic acid.
AB  - Crystal structures of the high-temperature phases of odd-numbered fatty acids
      (C(n)H(2n-1)OOH) from tridecanoic acid (C(13)H(25)OOH) to tricosanoic acid
      (C(23)H(45)OOH) are presented in this article. They have been determined from
      high-quality X-ray powder-diffraction patterns. Two types of high-temperature
      phases are adopted: one monoclinic A2/a with Z=8 for the fatty acids with n=13
      and n=15, denoted as C'', and one monoclinic P2(1)/a with Z=4 for the longer
      chain fatty acids, denoted as C'. It appears that the packing arrangement of the
      alkyl chains and of the carboxyl groups is similar in all of the structures.
      However, the arrangement at the methyl-group interface differs between the C' and
      C'' forms. A survey of the intermolecular interactions involved in these
      polymorphs coupled with a study of the effects of temperature on the structures
      have led us to a better understanding of the arrangement of the molecules within
      the high-temperature solid phases of odd-numbered fatty acids.

PMID- 17212367
TI  - Synthesis and properties of trigeminal tricationic ionic liquids.
AB  - Novel trigeminal tricationic ionic liquids (TTILs) have been successfully
      synthesized in high yields by means of Menschutkin quaternization via an S(N)1
      mechanism. This reaction presents a new convenient method for transforming
      glycerol into multifunctional compounds. The physical properties of a series of
      TTILs were characterized by using a variety of techniques. The prepared salts
      were tested for antimicrobial activity. Electrochemical characterization of TTILs
      was also performed, which allowed the estimation of the conductivity of these new
      compounds, to establish their electrochemical stability window and capacitance
      properties over a wide range of temperatures. A good correlation of the physical
      properties of TTILs with capacitance values was observed.

PMID- 17212368
TI  - Unusual kinematics-driven chemistry: cleaving C-H but not COO-H bonds with
      hyperthermal protons to synthesize tailor-made molecular films.
AB  - Unconventional reaction-design strategies have been developed to exploit the
      intriguing kinematics that occur when adsorbed organic molecules are bombarded by
      a beam of hyperthermal protons: kinematic energy transfer is only effective in H-
      >H collisions and thus only C-H bonds are cleaved. This process yields a cross
      linked molecular film with its chemistry governed by the selection of appropriate
      precursor molecules. Unlike the conventional wet-chemistry synthesis of cross
      linked polymeric films, this new route uses no chemical initiators, additives,
      nor catalysts, and only requires a proton beam with a kinetic energy of a few
      electron volts in a dry-process mode compatible with molecular-device
      fabrication. The reaction designs are expressed unconventionally: reaction energy
      is tuned by the kinetic energy of the proton beam and reactant supply is
      controlled precisely by the proton fluence. However, conventional considerations
      such as bond-strength effects on kinematic outcomes and branching-ratio
      statistics are also important and they can extend the reaction applicability of
      the kinematics concept. For example, taking advantage of the fact that COO-H
      bonds are stronger than C-H bonds, we show, with practical reaction conditions,
      synthesis results, and surface analysis using X-ray photoelectron spectroscopy
      and atomic force microscopy, that we can break C-H bonds without breaking COO-H
      and other bonds, in the production of cross-linked molecular layers with any
      desirable COOH concentration and with no ester nor other chemical contaminations.
      The new reaction-design strategies are also applicable to the synthesis of
      molecular layers with other functionalities such as OH, and to the synthesis of a
      mixture of functionalities, such as OH/COOH, with a controllable concentration
      ratio.

PMID- 17212369
TI  - Dipyrrolyl-functionalized bipyridine-based anion receptors for emission-based
      selective detection of dihydrogen phosphate.
AB  - New cationic anion receptors, based on the use of pyrrole-substituted bipyridine
      and coordinated to transition metals, are described. Specifically, polypyridine
      ruthenium and -rhodium cores have been functionalized to generate an anion
      binding site. The design was chosen to probe the influence of the pyrrole-to
      pyrrole separation on anion-binding affinities and selectivities; this distance
      is greater in the new systems of this report (receptors 1 and 2) relative to that
      present in related dipyrrolyl quinoxaline based receptors 3 and 4. Solution-phase
      anion-binding studies, carried out by means of (1)H NMR spectroscopic titrations
      in [D(6)]DMSO and isothermal titration calorimetry (ITC) in DMSO, reveal that 1
      and 2 bind most simple anions with substantially higher affinity than either 3 or
      4. In the case of chloride anion, structural studies, carried out by means of
      single-crystal X-ray diffraction analyses, are consistent with the solution-phase
      results and reveal that receptors 1 and 2 are both able to stabilize complexes
      with this halide anion in the solid state.

PMID- 17212370
TI  - Adaptive orientation of multifunctional nanowires for magnetic control of
      bioelectrocatalytic processes.

PMID- 17212371
TI  - Base-induced solvent switches in acid-base reactions.

PMID- 17212372
TI  - Identification of N-linked glycosylation sites in human nephrin using mass
      spectrometry.
AB  - Nephrin is a type-1 transmembrane glycoprotein and the first identified principal
      component of the glomerular filtration barrier. Ten potential asparagine (N)
      linked glycosylation sites have been predicted within the ectodomain of nephrin.
      However, it is not known which of these potential sites are indeed glycosylated
      and what type of glycans are involved. In this work, we have identified the
      terminal sugar residues on the ectodomain of human nephrin and utilized a
      straightforward and reliable mass spectrometry-based approach to selectively
      identify which of the ten predicted sites are glycosylated. Purified recombinant
      nephrin was subjected to peptide-N-glycosidase F (PNGase F) to enzymatically
      remove all the N-linked glycans. Since PNGase F is an amidase, the asparagine
      residues from which the glycans have been removed are deaminated to aspartic acid
      residues, resulting in an increase in the peptide mass with 1 mass unit.
      Following trypsin digestion, deglycosylated tryptic peptides were selectively
      identified by MALDI-TOF MS and their sequence was confirmed by tandem TOF/TOF.
      The 1 Da increase in peptide mass for each asparagine-to-aspartic acid
      conversion, along with preferential cleavage of the amide bond carboxyl-terminal
      to aspartic acid residues in peptides where the charge is immobilized by an
      arginine residue, was used as a diagnostic signature to identify the glycosylated
      peptides. Thus, nine of ten potential glycosylation sites in nephrin were
      experimentally proven to be modified by N-linked glycosylation.

PMID- 17212377
TI  - Photomechanics of liquid-crystalline elastomers and other polymers.
AB  - Muscle is a transducer that can convert chemical energy into mechanical motion.
      To construct artificial muscles, it is desirable to use soft materials with high
      mechanical flexibility and durability rather than hard materials such as metals.
      For effective muscle-like actuation, materials with stratified structures and
      high molecular orders are necessary. Liquid-crystalline elastomers (LCEs) are
      superior soft materials that possess both the order of liquid crystals and the
      elasticity of elastomers (as they contain polymer networks). With the aid of
      LCEs, it is possible to convert small amounts of external energy into macroscopic
      amounts of mechanical energy. In this Review, we focus on light as an energy
      source and describe the recent progress in the area of soft materials that can
      convert light energy into mechanical energy directly (photomechanical effect),
      especially the photomechanical effects of LCEs with a view to applications for
      light-driven LCE actuators.

PMID- 17212380
TI  - Prevalence-dependent diagnostic accuracy measures.
AB  - We study prevalence-dependent diagnostic accuracy measures, specifically,
      positive and negative predictive values. These measures permit an assessment of
      the clinical utility of diagnostic tests across populations with different
      disease prevalences. In many cases, prevalence may not be known with certainty
      and the evaluation of the diagnostic tests must account for this uncertainty. A
      sensitivity analysis may be desired across a prevalence continuum defining low to
      high-risk populations. For this scenario, simultaneous inference about the
      predictive values across a range of prevalences is proposed. For situations where
      a non-point prior distribution on prevalence is specified, we suggest inferences
      based on averaging the accuracy measures with respect to the prior, leading to
      simple numerical summaries. The methods are illustrated in a meta-analysis of
      diagnostic tests for intravascular device-related bloodstream infection, where
      the prevalence may vary widely both within and across populations.

PMID- 17212381
TI  - Leptin acts as a mitogenic and antiapoptotic factor for colonic cancer cells.
AB  - BACKGROUND: Obesity is associated with increased levels of leptin. The mitogenic
      actions of leptin have been identified in various cell types. Because obesity may
      be a risk factor for colonic cancer, the proliferative and antiapoptotic effects
      of leptin on colonic cancer cells and the role of mitogen-activated protein
      kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-K) signalling were
      investigated. METHODS: Three human colonic cancer cell lines (T(84), HT29/Cl.19A
      and Caco-2) were treated with leptin. Cell proliferation was measured using the
      XTT colorimetric assay and apoptosis by a cell death enzyme-linked immunosorbent
      assay. Inhibitors of MAPK and PI3-K were used to evaluate the role of these
      signalling pathways. Phosphorylation of the downstream components extracellular
      signal-regulated kinase (ERK) 1/2 and Akt was detected by western blotting.
      RESULTS: Leptin increased cell number in all cell lines in a dose-dependent
      manner and reduced the number of apoptotic cells in a cell line-dependent manner.
      Leptin also caused ERK1/2 and Akt phosphorylation. Pretreatment with inhibitors
      of MAPK and PI3-K inhibited these responses, attenuated the mitogenic action of
      leptin and abolished its antiapoptotic effects. CONCLUSION: Chronic increases in
      leptin concentration may enhance the growth of colonic cancers via MAPK and PI3-K
      pathways. These effects of leptin could provide a link between obesity and
      colonic cancer, and may represent a target for anticancer drug development.

PMID- 17212382
TI  - 15N-15N J-coupling across Hg(II): direct observation of Hg(II)-mediated T-T base
      pairs in a DNA duplex.

PMID- 17212383
TI  - Transmembrane helices have rough energy surfaces.

PMID- 17212384
TI  - Chiral cyanide-bridged Mn(II)Mn(III) ferrimagnets,
      [Mn(II)(HL)(H2O)][Mn(III)(CN)6].2H2O (L = S- or R-1,2-diaminopropane): syntheses,
      structures, and magnetic behaviors.

PMID- 17212385
TI  - Superexpanded Prussian-blue analogue with [Fe(CN)6]4-, [Nb6Cl12(CN)6]4-, and
      [Mn(salen)]+ as building units.

PMID- 17212386
TI  - Measurement of chiral-dependent magnetic anisotropy in carbon nanotubes.

PMID- 17212387
TI  - Dynamic assembly by electrokinetic microfluidics.

PMID- 17212388
TI  - Enantioselective Rauhut-Currier reactions promoted by protected cysteine.

PMID- 17212389
TI  - Examination of the new alpha-(2'Z-fluoro)vinyl trigger with lysine decarboxylase:
      the absolute stereochemistry dictates the reaction course.

PMID- 17212390
TI  - Reversibly caged glutamate: a photochromic agonist of ionotropic glutamate
      receptors.

PMID- 17212391
TI  - Electrochemical detection of parts-per-billion lead via an electrode-bound
      DNAzyme assembly.

PMID- 17212392
TI  - A 1:1 copper-dioxygen adduct is an end-on bound superoxo copper(II) complex which
      undergoes oxygenation reactions with phenols.

PMID- 17212393
TI  - Using beta-lactamase to trigger supramolecular hydrogelation.

PMID- 17212394
TI  - Endocytic delivery of vancomycin mediated by a synthetic cell surface receptor:
      rescue of bacterially infected Mammalian cells and tissue targeting in vivo.

PMID- 17212395
TI  - A double-stranded helix by complexation of two polymer chains with a helical
      supramolecular assembly.

PMID- 17212396
TI  - A-B-A-B-A block amphiphiles. Balance between hydrophilic and hydrophobic
      segmentation.

PMID- 17212397
TI  - Configuration change in [14]annulene requires mobius antiaromatic bond shifting.

PMID- 17212398
TI  - Cu(I) Tol-BINAP-catalyzed enantioselective Michael reactions of Grignard reagents
      and unsaturated esters.

PMID- 17212399
TI  - Reactivity of reduced nitroprusside, [Fe(CN)5NO*]3-, toward oxygen.

PMID- 17212400
TI  - Iridium-catalyzed C-C bond forming hydrogenation: direct regioselective reductive
      coupling of alkyl-substituted alkynes to activated ketones.

PMID- 17212401
TI  - Enantioselective synthesis of alpha-tertiary hydroxyaldehydes by palladium
      catalyzed asymmetric allylic alkylation of enolates.

PMID- 17212402
TI  - Ionic liquids: first direct determination of their cohesive energy.

PMID- 17212403
TI  - Vanadium-catalyzed asymmetric epoxidation of homoallylic alcohols.

PMID- 17212404
TI  - Direct catalytic asymmetric synthesis of anti-1,2-amino alcohols and syn-1,2
      diols through organocatalytic anti-Mannich and syn-aldol reactions.

PMID- 17212405
TI  - Chemoselective hydrogenation of imides catalyzed by Cp*Ru(PN) complexes and its
      application to the asymmetric synthesis of paroxetine.

PMID- 17212406
TI  - Enantioselective friedel-crafts reaction of electron-rich alkenes catalyzed by
      chiral Bronsted acid.

PMID- 17212407
TI  - The multiple amidation reactions catalyzed by Cobyric acid synthetase from
      Salmonella typhimurium are sequential and dissociative.

PMID- 17212408
TI  - 1H/2H NMR studies of geometric H/D isotope effects on the coupled hydrogen bonds
      in porphycene derivatives.
AB  - The 1H and 2H NMR spectra of porphycene (1), 2,3,6,7,12,13,16,17
      octaethylporphycene (2), 2,7,12,17-tetra-n-propylporphycene (3), and 2,7,12,17
      tetra-(tert-butyl)-3,6-13,16-dibenzo[cde;mno]porphycene (4) partially deuterated
      in the mobile proton sites are reported. These compounds exhibit two
      intramolecular NHN hydrogen bonds of increasing strength representing models of
      the concerted HH transfer in the parent compound, porphycene. The 1H chemical
      shifts of the mobile protons are correlated with the difference of the energies
      of the amino- and imino-N1s orbitals reported by Ghosh A.; Moulder J.; Broring
      M.; Vogel E. Angew. Chem., Int. Ed. 2001, 113, 445-448. The chemical shifts of 4
      indicate a reduced contribution of the aromatic ring current as compared to the
      other compounds which is associated to the nonplanarity of this molecule. The
      primary H/D isotope effects on the chemical shifts give information about the
      primary, secondary, and vicinal geometric isotope effects of the two inner
      hydrogen bonds of porphycenes. The vicinal effects indicate a cooperative
      coupling of the two hydrogen bonds which may favor a concerted double proton
      transfer mechanism.

PMID- 17212409
TI  - Mechanistic study of precursor evolution in colloidal group II-VI semiconductor
      nanocrystal synthesis.
AB  - The molecular mechanism of precursor evolution in the synthesis of colloidal
      group II-VI semiconductor nanocrystals was studied using 1H, 13C, and 31P NMR
      spectroscopy and mass spectrometry. Tri-n-butylphosphine chalcogenides (TBPE; E =
      S, Se, Te) react with an oleic acid complex of cadmium or zinc (M-OA; M = Zn, Cd)
      in a noncoordinating solvent (octadecene (ODE), n-nonane-d20, or n-decane-d22),
      affording ME nanocrystals, tri-n-butylphosphine oxide (TBPO), and oleic acid
      anhydride ((OA)2O). Likewise, the reaction between trialkylphosphine selenide and
      cadmium n-octadecylphosphonic acid complex (Cd-ODPA) in tri-n-octylphosphine
      oxide (TOPO) produces CdSe nanocrystals, trialkylphosphine oxide, and anhydrides
      of n-octadecylphosphonic acid. The disappearance of tri-n-octylphosphine selenide
      in the presence of Cd-OA and Cd-ODPA can be fit to a single-exponential decay
      (kobs = (1.30 +/- 0.08) x 10-3 s-1, Cd-ODPA, 260 degrees C, and kobs = (1.51 +/-
      0.04) x 10-3 s-1, Cd-OA, 117 degrees C). The reaction approaches completion at 70
      80% conversion of TOPSe under anhydrous conditions and 100% conversion in the
      presence of added water. Activation parameters for the reaction between TBPSe and
      Cd-OA in n-nonane-d20 were determined from the temperature dependence of the
      TBPSe decay over the range of 358-400 K (deltaH++ = 62.0 +/- 2.8 kJ.mol-1,
      deltaS++ = -145 +/- 8 J.mol-1.K-1). A reaction mechanism is proposed where
      trialkylphsophine chalcogenides deoxygenate the oleic acid or phosphonic acid
      surfactant to generate trialkylphosphine oxide and oleic or phosphonic acid
      anhydride products. Results from kinetics experiments suggest that cleavage of
      the phosphorus chalcogenide double bond (TOP=E) proceeds by the nucleophilic
      attack of phosphonate or oleate on a (TOP=E)-M complex, generating the initial M
      E bond.

PMID- 17212410
TI  - High energy and quantum efficiency in photoinduced charge separation.
AB  - Supramolecular triad assemblies consisting of a central trisbipyridine
      ruthenium(II) chromophore (C2+) with one or more appended phenothiazine electron
      donors (D) and a diquat-type electron acceptor (A2+) have been shown to form long
      lived photoinduced charge separated states (CSS) with unusually and consistently
      high quantum efficiency. Up to now, there has been no understanding for why these
      large efficiencies (often close to unity) are achieved across this entire class
      of triads when other, seemingly similar systems are often much less efficient. In
      the present study, using a bimolecular system consisting of a chromophore
      acceptor diad (C2+-A2+) and an N-methylphenothiazine donor, we demonstrate that a
      ground-state association exists between the RuL3(2+) and the phenothiazine prior
      to photoexcitation. It is this association process that is responsible for the
      efficient CSS formation in the bimolecular system and, by inference, also must be
      an essential factor in the fully intramolecular process occurring with the D-C2+
      A2+ triad analogues.

PMID- 17212411
TI  - Modulation of fluorescence through coassembly of molecules in organic
      nanostructures.
AB  - This paper describes the fluorescence of bimolecular coassemblies that form one
      dimensional nanostructures. One molecule is a fluorescent peptide amphiphile
      containing its branched stilbene chromophore covalently linked to the hydrophilic
      end of the amphiphile, and the second molecule is a shorter, nonfluorescent
      peptide amphiphile of complementary charge. Using circular dichroism we observe
      that mixing both molecules results in coassemblies that exhibit a beta-sheet
      signature in the peptide region indicative of these types of nanostructures. The
      nature of the coassembly is dependent on the molar ratio of each component, and
      the changing CD spectra suggest the formation of domains along the length of the
      nanofibers with decreasing concentrations of the fluorescent component. In
      coassemblies with dilute concentrations of the fluorophore, we observe an
      increase in fluorescence intensity and quantum yield, as well as chiral transfer
      to the achiral segment of the fluorescent peptide amphiphile. The coassemblies
      studied containing a fluorescent component at a low molar ratio exhibit
      fluorescence resonance energy transfer to fluorescent acceptors in solution. When
      the nonfluorescent peptide amphiphile component is designed to bind the important
      bioactive polysaccharide heparin, a selective transfer of energy is observed
      between fluorescein-tagged heparin and the coassemblies in both dilute solution
      and in macroscopic gels.

PMID- 17212412
TI  - Singlet-state exchange NMR spectroscopy for the study of very slow dynamic
      processes.
AB  - Singlet states with lifetimes that are longer than spin-lattice relaxation times
      TS > T1 offer unique opportunities for studying very slow dynamic processes in
      solution-state NMR. A set of novel experiments can achieve broadband excitation
      of singlet states in pairs of coupled spins. The most elaborate of these
      experiments, two-dimensional singlet-state exchange spectroscopy (SS-EXSY), is
      independent of the offsets of the two spins, their relative chemical shifts, and
      their scalar couplings. The new methods open the way to study very slow chemical
      exchange or translational diffusion using mixing times taum = Ts >> T1. The
      lifetimes TS of singlet states of pairs of protons in a partially deuterated
      saccharide are shown to be longer than the longitudinal proton relaxation times
      T1 in the same compound by a factor of ca. 37.

PMID- 17212413
TI  - 17O magic angle spinning NMR studies of Bronsted acid sites in zeolites HY and
      HZSM-5.
AB  - High-resolution 17O/1H double resonance NMR spectra were obtained for two
      zeolites, one with a low Si/Al ratio (zeolite HY) and one with a high Si/Al ratio
      (HZSM-5), to investigate their local structure and Bronsted acidity. Two
      different oxygen signals, corresponding to Bronsted acid sites in supercages and
      sodalite cages of zeolite HY were readily resolved in the two-dimensional (2-D)
      1H-17O heteronuclear correlation (HETCOR) NMR spectra allowing the 17O isotropic
      chemical shift (deltaCS) and quadrupolar coupling parameters (quadrupolar
      coupling constant, QCC, and asymmetry parameter, eta) for the two oxygen atoms to
      be extracted. Similar experiments for HZSM-5 showed that the sites in this system
      are associated with a much larger distribution in NMR parameters than found in
      HY. 17O-1H rotational echo double resonance (REDOR) NMR was applied to probe the
      O-H distances in zeolites HY and HZSM-5. Weaker 17O-1H dephasing was observed for
      zeolite HZSM-5 in comparison to that of HY, consistent with longer O-H bonds
      and/or increased proton mobility.

PMID- 17212414
TI  - A molecular keypad lock: a photochemical device capable of authorizing password
      entries.
AB  - This paper describes a new concept in the way information can be protected at the
      molecular scale. By harnessing the principles of molecular Boolean logic, we have
      designed a molecular device that mimics the operation of an electronic keypad
      lock, e.g., a common security circuit used for numerous applications, in which
      access to an object or data is to be restricted to a limited number of persons.
      What distinguishes this lock from a simple molecular logic gate is the fact that
      its output signals are dependent not only on the proper combination of the inputs
      but also on the correct order by which these inputs are introduced. In other
      words, one needs to know the exact passwords that open this lock. The different
      password entries are coded by a combination of two chemical and one optical input
      signals, which can activate, separately, blue or green fluorescence output
      channels from pyrene or fluorescein fluorophores. The information in each channel
      is a single-bit light output signal that can be used to authorize a user, to
      verify authentication of a product, or to initiate a higher process. This
      development not only opens the way for a new class of molecular decision-making
      devices but also adds a new dimension of protection to existing defense
      technologies, such as cryptography and steganography, previously achieved with
      molecules.

PMID- 17212415
TI  - Direct demonstration of enhanced diffusion in mesoporous ZSM-5 zeolite obtained
      via controlled desilication.
AB  - A 2 orders of magnitude gas transport improvement in a medium pore ZSM-5 zeolite
      has been achieved upon introduction of intracrystalline mesoporosity in gradient
      free crystals by desilication post-treatment in alkaline medium.

PMID- 17212416
TI  - Rotational-echo double-resonance NMR distance measurements for the tubulin-bound
      Paclitaxel conformation.
AB  - The important anticancer drug Taxol (paclitaxel, PTX) owes its unique activity to
      its ability to bind to tubulin in a stoichiometric ratio and promote its assembly
      into microtubules. The conformation of the microtubule-bound drug has been the
      focus of numerous research efforts, since the inability of polymerized tubulin to
      form crystals precludes structure proof by X-ray crystallography. Likewise,
      although the alpha,beta-tubulin dimer structure has been solved by electron
      crystallography, the 3.7 A resolution is too low to permit direct determination
      of either ligand conformation or binding pose. In this article, we present
      experimental results from 2H{19F} REDOR NMR that provide direct confirmation that
      paclitaxel adopts a T-shaped conformation when it is bound to tubulin.

PMID- 17212417
TI  - Organometallics meet colloid chemistry: a case study in three phases based on
      molecular carbonyl precursors containing zinc and manganese.
AB  - Two organometallic compounds containing zinc and manganese in different ratios
      are used as single-source precursors for the preparation of various new,
      bimetallic oxide materials with nanoscaled dimensions. It is shown that the
      materials synthesis can be performed in the solid-state, the liquid-phase, and
      even in the gas-phase. The molecular composition of the precursors determines the
      composition of the resulting materials. In addition, two novel methods for the
      preparation of highly crystalline metal oxide colloids are presented: The
      coupling between a gas-phase process and a colloidal approach, and the
      application of ozone as an oxidant for the transformation of metal carbonyls into
      oxides in the liquid phase.

PMID- 17212418
TI  - Progress toward a rationally designed, chemically powered rotary molecular motor.
AB  - Building on prototype 1, which achieves 120 degrees of phosgene-powered
      unidirectional rotation to rotamer 6 (see Figure 5 in the full article), 7 was
      designed to accomplish repeated unidirectional rotation (see Scheme 7). Compound
      7 contains an amino group on each blade of the triptycene and a 4
      (dimethylamino)pyridine (DMAP) unit to selectively deliver phosgene (or its
      equivalent) to the amine in the "firing position". The synthesis of 7 is
      described: the key constructive steps are a benzyne addition to an anthracene to
      generate the triptycene, a stilbene photocyclization to construct the helicene,
      and a Stille coupling to incorporate the DMAP unit. The DMAP unit was shown to
      regioselectively relay 1,1'-carbonyldiimidazole (but not phosgene) to the
      proximal amino group, as designed, but rotation of the triptycene does not occur.
      Extensive attempts to troubleshoot the problem led to the conclusion that the
      requisite intramolecular urethane formation, as demonstrated in the prototype (1 
      -> 4), does not occur with 7 (to give 85) or 97 (to give 100). We speculate that
      either (i) hydrogen bonding between the hydroxypropyl group and functionality
      present in 7 but absent from 1 or (ii) a Burgi-Dunitz (or similar) interaction
      involving the DMAP (see 106) prevents achievement of a conformation conducive to
      intramolecular urethane formation.

PMID- 17212419
TI  - Proton shuttles and phosphatase activity in soluble epoxide hydrolase.
AB  - Recently, a novel metal Mg2+-dependent phosphatase activity has been discovered
      in the N-terminal domain of the soluble epoxide hydrolase (sEH), opening a new
      branch of fatty acid metabolism and providing an additional site for drug
      targeting. Importantly, the sEH N-terminal fold belongs to the haloacid
      dehalogenase (HAD) superfamily, which comprises a vast majority of
      phosphotransferases. Herein, we present the results of a computational study of
      the sEH phosphatase activity, which includes classical molecular dynamics (MD)
      simulations and mixed quantum mechanical/molecular mechanics (QM/MM)
      calculations. On the basis of experimental results, a two-step mechanism has been
      proposed and herein investigated: (1) phosphoenzyme intermediate formation and
      (2) phosphoenzyme intermediate hydrolysis. Building on our earlier work, we now
      provide a detailed description of the reaction mechanism for the whole catalytic
      cycle along with its free energy profile. The present computations suggest
      metaphosphate-like transition states for these phosphoryl transfers. They also
      reveal that the enzyme promotes water deprotonation and facilitates shuttling of
      protons via a metal-ligand connecting water bridge (WB). These WB-mediated proton
      shuttles are crucial for the activation of the solvent nucleophile and for the
      stabilization of the leaving group. Moreover, due to the conservation of
      structural features in the N-terminal catalytic site of sEH and other members of
      the HAD superfamily, we suggest a generalization of our findings to these other
      metal-dependent phosphatases.

PMID- 17212420
TI  - The role of achiral pyrazolidinone templates in enantioselective Diels-Alder
      reactions: scope, limitations, and conformational insights.
AB  - We have evaluated the role of achiral pyrazolidinone templates in conjunction
      with chiral Lewis acids in room temperature, enantioselective Diels-Alder
      cycloadditions. The role of the fluxional N(1) substituent was examined, with the
      bulky 1-naphthylmethyl group providing enantioselectivities up to 99% ee, while
      templates with smaller fluxional groups gave lower selectivities. High
      selectivities were also observed in reactions of 7d with chiral Lewis acids
      derived from relatively small chiral ligands, suggesting the pyrazolidinone
      templates are capable of relaying stereochemical information from the ligand to
      the reaction center. Lewis acids capable of adapting square planar geometries,
      such as Cu(OTf)2, Cu(ClO4)2, and Pd(ClO4)2, were found to be particularly
      effective at providing high selectivities. Additionally, substitution at the C-5
      position of the pyrazolidinone templates has been shown to be critical for
      optimal selectivity. Reactions of the optimal pyrazolidinone appended with a
      number of common dienophiles and various dienes demonstrate the utility of this
      achiral template. Furthermore, catalytic loadings could be lowered to 2.5 mol %
      with essentially no loss in selectivity. Pi-Pi interactions were evaluated as a
      means to explain the unusually high selectivity observed at room temperature.
      Finally, non-C2-symmetric ligands were employed as a test to determine if chiral
      relay was operative.

PMID- 17212421
TI  - Isomerization dynamics and control of the eta2/N equilibrium for pyridine
      complexes.
AB  - A series of pyridine complexes are prepared of the general form
      TpW(NO)(PMe3)(pyr) where pyr is either pyridine or a substituted pyridine.
      Depending on substitution pattern, the pyridine can be either N- or eta2
      coordinated, and the role of the pyridine substituents and metal oxidation state
      in determining this equilibrium is explored. For eta2-pyridine complexes, the
      substituent pattern and solubility characteristics also determine the ratio of
      coordination diastereomers. Rates of both intra- and interfacial linkage
      isomerizations are explored along with the pyridine rotational barrier. This
      study is supported by DFT calculations and X-ray data and includes
      characterization of both eta2-pyridine and eta2-pyridinium complexes.

PMID- 17212422
TI  - Interplay among folding, sequence, and lipophilicity in the antibacterial and
      hemolytic activities of alpha/beta-peptides.
AB  - Host-defense peptides inhibit bacterial growth but manifest relatively little
      toxicity toward eukaryotic cells. Many host-defense peptides adopt alpha-helical
      conformations in which cationic side chains and lipophilic side chains are
      segregated to distinct regions of the molecular surface ("globally amphiphilic
      helices"). Several efforts have been made to develop unnatural oligomers that
      mimic the selective antibacterial activity of host-defense peptides; these
      efforts have focused on the creation of molecules that are globally amphiphilic
      in the preferred conformation. One such endeavor, from our laboratories, focused
      on helix-forming alpha/beta-peptides, i.e., oligomers containing a 1:1 pattern of
      alpha- and beta-amino acid residues in the backbone [Schmitt, M. A.; Weisblum,
      B.; Gellman, S. H. J. Am. Chem. Soc. 2004, 126, 6848-6849]. We found,
      unexpectedly, that the most favorable biological activity profile was displayed
      by a "scrambled" sequence, which was designed not to be able to form a globally
      amphiphilic helix. Here we report new data, involving an expanded set of
      alpha/beta-peptides, from experiments designed to elucidate the origins of this
      surprising result. In addition, we evaluate the susceptibility of alpha/beta
      peptides to proteolytic degradation. Our results support the hypothesis that the
      ability to adopt a globally amphiphilic helical conformation is not a
      prerequisite for selective antibacterial activity. This conclusion represents a
      significant advance in our understanding of the relationship among molecular
      composition, conformation, and biological activity. Our results should therefore
      influence the design of other unnatural oligomers intended to function as
      antibacterial agents.

PMID- 17212423
TI  - Total synthesis of abyssomicin C, atrop-abyssomicin C, and abyssomicin D:
      implications for natural origins of atrop-abyssomicin C.
AB  - In this article, the total syntheses of the antibiotic abyssomicin C (1) and its
      biologically inactive sibling abyssomicin D (3) are described. A number of
      unforseen roadblocks in our synthetic plan encouraged innovation, which
      culminated in the discovery of a new Lewis acid-templated Diels-Alder reaction.
      En route to abyssomicin C, we prepared and characterized its stable
      conformational isomer atrop-abyssomicin C (57), which in the presence of a strong
      acid underwent an unusual interconversion with the targeted natural product.
      Close inspection of the X-ray crystallographic structures of these compounds led
      to hypotheses on the mechanism of their interconversion. Attempted reduction of
      both atropisomers revealed that atrop-abyssomicin C afforded abyssomicin D much
      more readily, suggesting that this previously unknown atropisomer may be
      synthesized by the host organism and serves as a direct precursor of abyssomicin
      D. Finally, to gain insight into the mechanism of antiobiotic activity, several
      synthetic intermediates and designed analogues were evaluated for biological
      activity.

PMID- 17212424
TI  - Organocatalytic asymmetric direct alpha-alkynylation of cyclic beta-ketoesters.
AB  - The first organocatalytic enantioselective direct alpha-alkynylation of beta
      ketoesters and 3-acyl oxindoles is described. It is demonstrated that activated
      beta-halo-alkynes undergo nucleophilic acetylenic substitution catalyzed by
      chiral phase-transfer compounds to afford the alkynylated products in high yields
      and excellent enantioselectivities. The potential of the reaction is first
      demonstrated for various alkynylating reagents having chloride and bromide as the
      leaving groups and substituents such as allyl and alkyl esters, amides, ketones,
      and sulfones. These reactions proceed with 74-99% yield and 88-97% ee. Then the
      scope in nucleophile is demonstrated for a large number of cyclic beta-ketoesters
      with various ring-sizes and for oxindoles as well. The corresponding optically
      active products are formed in high yields and with enantioselectivities up to 98%
      ee. The procedure allows for the stereocontrolled attachment of an ethynyl unit
      in the alpha-position to the carbonyl compound by facile removal of the
      activating group, and this has been demonstrated for a number of the optically
      active allyl esters. Furthermore, the synthesis of optically active 1,4-enynes is
      also shown. The isolation and characterization by X-ray analysis of the catalyst
      with p-nitrophenolate as the counterion allowed us to propose a model of the
      catalyst-substrate intermediate which might account for the observed
      enantioselectivity of the organocatalytic enantioselective alpha-alkynylation
      reaction. Furthermore, it is suggested that this intermediate is also the
      reactive species for a number of other electrophiles adding to beta-ketoesters
      giving enantioselectivities in the range of 90-98% ee.

PMID- 17212430
TI  - Hydrogen sieving and storage in fullerene intercalated graphite.
AB  - The geometrical properties of recently synthesised C60 intercalated in graphite
      have been confirmed by density-functional-based computer simulations. The
      capability of this material to store molecular hydrogen by physisorption is
      evaluated. While the material can sieve H2 from heavier molecular gases, our free
      energy calculations indicate that further tuning of the system by reducing the
      amount of intercalated fullerene cages is necessary to achieve H2 loadings which
      are interesting for technical applications.

PMID- 17212431
TI  - Nanocrystalline nanowires: I. Structure.
AB  - Geometric constructions of possible atomic arrangements are suggested for
      inorganic nanowires. These are fragments of bulk crystals, and can be called
      "nanocrystalline" nanowires (NCNW). To minimize surface polarity, nearly one
      dimensional formula units, oriented along the growth axis, generate NCNWs by
      translation and rotation.

PMID- 17212432
TI  - Nanocrystalline nanowires: 2. Phonons.
AB  - Nanocrystalline nanowires (NCNW) are fragments of bulk crystals that are infinite
      in only one direction. A construction is given for calculating eigenstates
      belonging to the symmetry labels (k,m) (wavevector and rotational quantum
      number). Vibrational harmonic eigenstates are worked out explicitly for a simple
      model, illustrating the general results: the LA mode has m=0, while with
      sufficient rotational symmetry, the TA branch is doubly degenerate, has m=+/-1,
      and has quadratic dispersion with k for k less than the reciprocal diameter of
      the NCNW. The twiston branch (a fourth Goldstone boson) is an acoustic m=0
      branch, additional to the LA and two TA branches.

PMID- 17212433
TI  - Nanoscopically flat open-ended single-walled carbon nanotube substrates for
      continued growth.
AB  - Continued growth is a way of growing nanotubes targeted to produce continuous and
      chirality-controlled single-walled carbon nanotube (SWNT) materials. This growth
      method strongly depends on efficient preparation of open-ended SWNT substrates.
      Nanoscopically flat open-ended SWNT substrates have been prepared by cutting the
      SWNT spun fiber with a focused ion beam cutting technique and followed by etching
      schemes for cleaning amorphous carbon and opening the ends of the SWNTs. The open
      ends were effectively characterized through selective etch back of open SWNT ends
      by carbon dioxide gas at 950 degrees C. High density continued growth was
      demonstrated from these nanoscopically flat open-ended substrates.

PMID- 17212434
TI  - High-performance carbon nanotube field effect transistors with a thin gate
      dielectric based on a self-assembled monolayer.
AB  - Individual single-walled carbon nanotube (SWCNT) field effect transistors (FETs)
      with a 2 nm thick silane-based organic self-assembled monolayer (SAM) gate
      dielectric have been manufactured. The FETs exhibit a unique combination of
      excellent device performance parameters. In particular, they operate with a gate
      source voltage of only -1 V and exhibit good saturation, large transconductance,
      and small hysteresis (<or=100 mV), as well as a very low subthreshold swing (60
      mV/dec) under ambient conditions. The SAM-based gate dielectric opens the
      possibility of fabricating transistors operating at low voltages and constitutes
      a major step toward nanotube-based flexible electronics.

PMID- 17212435
TI  - Lambda/4 resonance of an optical monopole antenna probed by single molecule
      fluorescence.
AB  - We present a resonant optical nanoantenna positioned at the end of a metal-coated
      glass fiber near-field probe. Antenna resonances, excitation conditions, and
      field localization are directly probed in the near field by single fluorescent
      molecules and compared to finite integration technique simulations. It is shown
      that the antenna is equivalent to its radio frequency analogue, the monopole
      antenna. For the right antenna length and local excitation conditions, antenna
      resonances occur that lead to an enhanced localized field near the antenna apex.
      Direct mapping of this field with single fluorescent molecules reveals a spatial
      localization of 25 nm, demonstrating the importance of such antennas for
      nanometer resolution optical microscopy.

PMID- 17212436
TI  - Silicon nanowire band gap modification.
AB  - Band gap modification for small-diameter (approximately 1 nm) silicon nanowires
      resulting from the use of different species for surface termination is
      investigated by density functional theory calculations. Because of quantum
      confinement, small-diameter wires exhibit a direct band gap that increases as the
      wire diameter narrows, irrespective of surface termination. This effect has been
      observed in previous experimental and theoretical studies for hydrogenated wires.
      For a fixed cross-section, the functional group used to saturate the silicon
      surface significantly modifies the band gap, resulting in relative energy shifts
      of up to an electronvolt. The band gap shifts are traced to details of the
      hybridization between the silicon valence band and the frontier orbitals of the
      terminating group, which is in competition with quantum confinement.

PMID- 17212437
TI  - Morphology- and orientation-controlled gallium arsenide nanowires on silicon
      substrates.
AB  - GaAs nanowires were epitaxially grown on Si(001) and Si(111) substrates by using
      Au-catalyzed vapor-liquid-solid (VLS) growth in a solid source molecular beam
      epitaxy system. Scanning electron microscopy analysis revealed that almost all
      the GaAs nanowires were grown along <111> directions on both Si substrates for
      growth conditions investigated. The GaAs nanowires had a very uniform diameter
      along the growth direction. X-ray diffraction data and transmission electron
      microscopy analysis revealed that the GaAs<111> nanowires had a mixed crystal
      structure of the hexagonal wurtzite and the cubic zinc-blende. Current-voltage
      characteristics of junctions formed by the epitaxially grown GaAs nanowires and
      the Si substrate were investigated by using a current-sensing atomic force
      microscopy.

PMID- 17212438
TI  - DNA nucleoside interaction and identification with carbon nanotubes.
AB  - We investigate the interaction of individual DNA nucleosides with a carbon
      nanotube (CNT) in vacuum and in the presence of external gate voltage. We propose
      a scheme to discriminate between nucleosides on CNTs based on measurement of
      electronic features through a local probe such as scanning tunneling
      spectroscopy. We demonstrate through quantum mechanical calculations that these
      measurements can achieve 100% efficiency in identifying DNA bases. Our results
      support the practicality of ultrafast DNA sequencing using electrical
      measurements.

PMID- 17212439
TI  - Factors controlling the electrodeposition of metal nanoparticles on pristine
      single walled carbon nanotubes.
AB  - The electrodeposition of metal (Pd and Pt) nanoparticles on networks of pristine
      single walled carbon nanotubes (SWNTs) has been investigated using a
      microelectrochemical cell. A microcapillary containing electrolyte solution and a
      reference electrode is contacted with a silicon oxide substrate bearing a SWNT
      network, connected as the working electrode. Electrodeposition is promoted by
      applying a potential between the SWNT network and the reference electrode. By
      combination of analysis of the resulting current-time curves with atomic force
      microscopy and field emission scanning electron microscopy imaging of the network
      surfaces after electrodeposition, the nature of metal nanoparticle formation on
      SWNTs has been elucidated. In particular, the parameters controlling nanoparticle
      number density, distribution, and size have been identified, with short
      deposition times and high driving forces favoring the formation of ultrasmall
      particles at high density. Capacitance and network resistance effects are
      minimized in the microcapillary configuration, making it possible to accurately
      analyze short time-scale deposition processes (millisecond time scale).
      Furthermore, it is also possible to make many measurements on a pristine sample,
      simply by moving the position of the microcapillary to a new location on the
      substrate.

PMID- 17212440
TI  - Nanorobotic spot welding: controlled metal deposition with attogram precision
      from copper-filled carbon nanotubes.
AB  - With the continuing development of bottom-up nanotechnology fabrication
      processes, spot welding can play a role similar to its macro counterpart for the
      interconnection of nano building blocks for the assembly of nanoelectronics and
      nanoelectromechanical systems (NEMS). Spot welding using single-crystalline
      copper-filled carbon nanotubes (CNTs) is investigated experimentally using
      nanorobotic manipulation inside a transmission electron microscope (TEM).
      Controlled melting and flowing of copper inside nanotube shells are realized by
      applying bias voltages between 1.5 and 2.5 V. The average mass flow rate of the
      copper was found to be 120 ag/s according to TEM video imaging (measured visually
      at approximately 11.6 nm/s through the CNT). Successful soldering of a copper
      filled CNT onto another CNT shows promise for nano spot welding and thermal dip
      pen lithography.

PMID- 17212441
TI  - Tip cooling effect and failure mechanism of field-emitting carbon nanotubes.
AB  - The cooling effect accompanying field electron emission has been considered for a
      single carbon nanotube (CNT) used as a field emission (FE) electron source. An
      improved model for the failure mechanism of field emitting CNTs has been proposed
      and validated. Our model predicts a maximum temperature (T-max) located at an
      interior point rather than the tip of the CNTs, and the failure of the CNT
      emitters tends to take place at the T-max point, inducing a segment by segment
      breakdown process. A combination of Joule heating and electrostatic force effect
      is proposed responsible for initiating the failure of the field emitting CNT and
      validated by in situ FE observation.

PMID- 17212442
TI  - Enhanced charge-collection efficiencies and light scattering in dye-sensitized
      solar cells using oriented TiO2 nanotubes arrays.
AB  - We report on the microstructure and dynamics of electron transport and
      recombination in dye-sensitized solar cells (DSSCs) incorporating oriented TiO2
      nanotube (NT) arrays. The morphology of the NT arrays, which were prepared from
      electrochemically anodized Ti foils, were characterized by scanning and
      transmission electron microscopies. The arrays were found to consist of closely
      packed NTs, several micrometers in length, with typical wall thicknesses and
      intertube spacings of 8-10 nm and pore diameters of about 30 nm. The calcined
      material was fully crystalline with individual NTs consisting of about 30 nm
      sized crystallites. The transport and recombination properties of the NT and
      nanoparticle (NP) films used in DSSCs were studied by frequency-resolved
      modulated photocurrent/photovoltage spectroscopies. While both morphologies
      display comparable transport times, recombination was much slower in the NT
      films, indicating that the NT-based DSSCs have significantly higher charge
      collection efficiencies than their NP-based counterparts. Dye molecules were
      shown to cover both the interior and exterior walls of the NTs. Analysis of
      photocurrent measurements indicates that the light-harvesting efficiencies of NT
      based DSSCs were higher than those found for DSSCs incorporating NPs owing to
      stronger internal light-scattering effects.

PMID- 17212444
TI  - Probing spin accumulation in Ni/Au/Ni single-electron transistors with efficient
      spin injection and detection electrodes.
AB  - We have investigated spin accumulation in Ni/Au/Ni single-electron transistors
      assembled by atomic force microscopy. The fabrication technique is unique in that
      unconventional hybrid devices can be realized with unprecedented control,
      including real-time tunable tunnel resistances. A grid of Au disks, 30 nm in
      diameter and 30 nm thick, is prepared on a SiO2 surface by conventional e-beam
      writing. Subsequently, 30 nm thick ferromagnetic Ni source, drain, and side-gate
      electrodes are formed in similar process steps. The width and length of the
      source and drain electrodes were different to exhibit different coercive
      switching fields. Tunnel barriers of NiO are realized by sequential Ar and O2
      plasma treatment. By use of an atomic force microscope with specially designed
      software, a single nonmagnetic Au nanodisk is positioned into the 25 nm gap
      between the source and drain electrodes. The resistance of the device is
      monitored in real time while the Au disk is manipulated step-by-step with
      angstrom-level precision. Transport measurements in magnetic field at 1.7 K
      reveal no clear spin accumulation in the device, which can be attributed to fast
      spin relaxation in the Au disk. From numerical simulations using the rate
      equation approach of orthodox Coulomb blockade theory, we can put an upper bound
      of a few nanoseconds on the spin-relaxation time for electrons in the Au disk. To
      confirm the magnetic switching characteristics and spin injection efficiency of
      the Ni electrodes, we fabricated a test structure consisting of a Ni/NiO/Ni
      magnetic tunnel junction with asymmetric dimensions of the electrodes similar to
      those of the single-electron transistors. Magnetoresistance measurements on the
      test device exhibited clear signs of magnetic reversal and a maximum tunneling
      magnetoresistance of 10%, from which we deduced a spin polarization of about 22%
      in the Ni electrodes.

PMID- 17212443
TI  - The SERS and TERS effects obtained by gold droplets on top of Si nanowires.
AB  - We show that hemispherical gold droplets on top of silicon nanowires when grown
      by the vapor-liquid-solid (VLS) mechanism, can produce a significant enhancement
      of Raman scattered signals. Signal enhancement for a few or even just single gold
      droplets is demonstrated by analyzing the enhanced Raman signature of malachite
      green molecules. For this experiment, trenches (approximately 800 nm wide) were
      etched in a silicon-on-insulator (SOI) wafer along <110> crystallographic
      directions that constitute sidewalls ({110} surfaces) suitable for the growth of
      silicon nanowires in <111> directions with the intention that the gold droplets
      on the silicon nanowires can meet somewhere in the trench when growth time is
      carefully selected. Another way to realize gold nanostructures in close vicinity
      is to attach a silicon nanowire with a gold droplet onto an atomic force
      microscopy (AFM) tip and to bring this tip toward another gold-coated AFM tip
      where malachite green molecules were deposited prior to the measurements. In both
      experiments, signal enhancement of characteristic Raman bands of malachite green
      molecules was observed. This indicates that silicon nanowires with gold droplets
      atop can act as efficient probes for tip-enhanced Raman spectroscopy (TERS). In
      our article, we show that a nanowire TERS probe can be fabricated by welding
      nanowires with gold droplets to AFM tips in a scanning electron microscope (SEM).
      TERS tips made from nanowires could improve the spatial resolution of Raman
      spectroscopy so that measurements on the nanometer scale are possible.

PMID- 17212445
TI  - Excitons and Peierls distortion in conjugated carbon nanotubes.
AB  - We investigate coupled excitonic and vibrational effects in carbon nanotubes
      using a time-dependent Hartree-Fock approach. The results reveal intricate
      details of excited-state dynamics. In the ground state, spontaneous uneven
      distribution of the pi electrons over the bonds (i.e., Peierls dimerization) is
      observed throughout the entire nanotube, particularly in large-radius CNTs.
      However, we demonstrate that vibrational relaxation following photoexcitations
      leads to substantial local distortion of the tube surface, overriding the Peierls
      dimerization. This mutually affects the electronic system, resulting in localized
      states (self-trapped excitons). These phenomena critically control photoinduced
      dynamics and charge transport in nanotube materials.

PMID- 17212446
TI  - Optical and magnetic resonance imaging of cell death and platelet activation
      using annexin a5-functionalized quantum dots.
AB  - A quantum-dot-based nanoparticle is presented, allowing visualization of cell
      death and activated platelets with fluorescence imaging and MRI. The particle
      exhibits intense fluorescence and a large MR relaxivity (r1) of 3000-4500 mM-1 s
      1 per nanoparticle due to a newly designed construct increasing the gadolinium
      DTPA load. The nanoparticle is suitable for both anatomic and subcellular imaging
      of structures in the vessel wall and is a promising bimodal contrast agent for
      future in vivo imaging studies.

PMID- 17212447
TI  - Onset of plasticity in gold nanopillar compression.
AB  - On the basis of a series of molecular dynamics simulations of the compressive
      deformation of <111>-oriented gold nanopillars, we demonstrate that slip
      nucleates at surface features for which the amplitude of thermal vibrations is a
      maximum. This leads to a yield stress which can be either a linear or parabolic
      function of temperature, depending on the strength with which atoms are bound to
      the surface. Changing the surface structure by removing weakly bound atoms
      produces a striking rise in yield strength and a change in its temperature
      dependence.

PMID- 17212448
TI  - Effect of quantum and dielectric confinement on the exciton-exciton interaction
      energy in type II core/shell semiconductor nanocrystals.
AB  - We study theoretically two electron-hole pair states (biexcitons) in core/shell
      hetero-nanocrystals with type II alignment of energy states, which promotes
      spatial separation of electrons and holes. To describe Coulomb interactions in
      these structures, we apply first-order perturbation theory, in which we use an
      explicit form of the Coulomb-coupling operator that takes into account interface
      polarization effects. This formalism is used to analyze the exciton-exciton
      interaction energy as a function of the core and shell sizes and their dielectric
      properties. Our analysis shows that the combined contributions from quantum and
      dielectric confinement can result in strong exciton-exciton repulsion with giant
      interaction energies on the order of 100 meV. Potential applications of strongly
      interacting biexciton states include such areas as lasing, nonlinear optics, and
      quantum information.

PMID- 17212449
TI  - Using gold nanorods to probe cell-induced collagen deformation.
AB  - In biological tissue, complex mechanisms of cellular response are closely linked
      to the mechanical environment that cells experience. The key to understanding
      these mechanisms may lie in measurement of local mechanical fields near living
      cells and between cells. We have developed a novel optical measurement technique
      which combines the light elastically scattered from gold nanorods with digital
      image analysis to track local deformations that occur in vitro between cells, in
      real time, under darkfield optical microscopy. We find that measurable tension
      and compression exist in the intercellular matrix at the length scale of
      micrometers, as the cells assess, adapt, and rearrange their environment.

PMID- 17212450
TI  - Efficient and sensitive capacitive readout of nanomechanical resonator arrays.
AB  - Here we describe all-electronic broadband motion detection in radio frequency
      nanomechanical resonators. Our technique relies upon the measurement of small
      motional capacitance changes using an LC impedance transformation network. We
      first demonstrate the technique on a single doubly clamped beam resonator with a
      side gate over a wide range of temperatures from 20 mK to 300 K. We then apply
      the technique to accomplish multiplexed readout of an array of individually
      addressable resonators, all embedded in a single high-frequency circuit. This
      technique may find use in a variety of applications ranging from ultrasensitive
      mass and force sensing to quantum information processing.

PMID- 17212451
TI  - Ordered binary arrays of Au nanoparticles derived from colloidal lithography.
AB  - By using angle-resolved colloidal lithography and O2-plasma etched bilayers of
      hexagonally packed spheres as templates, we succeeded in fabrication of highly
      ordered binary arrays of gold nanoparticles with varied shapes, for instance,
      with a shuttlecock-like shape composed of a small crescent-shaped nanoparticle
      and a big fan-shaped one. The size and shape of both small and big nanoparticles
      obtained were manipulated by the plasma etching period and the incidence angle of
      Au vapor flow. The subsequent thermal annealing led to binary arrays of round Au
      nanoparticles with a rather narrow distribution in terms of size and shape. Our
      approach should pave a simple and versatile colloidal way to form binary
      nanoparticle arrays, holding immense promise for technical applications such as
      nanoelectronics and nanophotonics.

PMID- 17212452
TI  - Molecular beam deposition of DNA nanometer films.
AB  - The development of novel photonic devices which incorporate biological materials
      is strongly tied to the development of thin film forming processes. Solution
      based ("wet") processes when used with biomaterials in device fabrication suffer
      from dissolution of underlying layers, incompatibility with clean environment,
      inconsistent film properties, etc. We have investigated ultra-high-vacuum
      molecular beam deposition of surfactant-modified deoxyribonucleic acid (DNA). We
      have obtained effective deposition rates of approximately 0.1-1 A/s, enabling
      reproducible and controllable deposition of nanometer-scale films.

PMID- 17212453
TI  - Coherent acoustic vibration of metal nanoshells.
AB  - Using time-resolved pump-probe spectroscopy, we have performed the first
      investigation of the vibrational modes of gold nanoshells. The fundamental
      isotropic mode launched by a femtosecond pump pulse manifests itself in a
      pronounced time-domain modulation of the differential transmission probed at the
      frequency of nanoshell surface plasmon resonance. The modulation amplitude is
      significantly stronger, and the period is longer than that in a gold nanoparticle
      of the same overall size, in agreement with theoretical calculations. This
      distinct acoustical signature of nanoshells provides a new and efficient method
      for identifying these versatile nanostructures and for studying their mechanical
      and structural properties.

PMID- 17212454
TI  - Two distinct buckling modes in carbon nanotube bending.
AB  - By using controlled SPM manipulation, carbon nanotubes have been continuously
      bent into a series of increasing angles, and two distinct buckling modes
      corresponding to "abrupt" and "gradual" buckle formation were observed through
      recording the height increment at the bend site during the loading process.
      Molecular dynamics simulation also found the two buckling modes in different
      types of carbon nanotubes, and their atomistic mechanism was revealed. Finally,
      the dependence of the critical buckling condition on diameters of carbon
      nanotubes was tentatively studied.

PMID- 17212455
TI  - Bifunctional magnetic silica nanoparticles for highly efficient human stem cell
      labeling.
AB  - A superparamagnetic iron oxide (SPIO) nanoparticle is emerging as an ideal probe
      for noninvasive cell tracking. However, its low intracellular labeling efficiency
      has limited the potential usage and has evoked great interest in developing new
      labeling strategies. We have developed fluorescein isothiocyanate (FITC)
      incorporated silica-coated core-shell SPIO nanoparticles, SPIO@SiO2(FITC), with
      diameters of 50 nm, as a bifunctionally magnetic vector that can efficiently
      label human mesenchymal stem cells (hMSCs), via clathrin- and actin-dependent
      endocytosis with subsequent intracellular localization in late
      endosomes/lysosomes. The uptake process displays a time- and dose-dependent
      behavior. In our system, SPIO@SiO2(FITC) nanoparticles induce sufficient cell MRI
      contrast at an incubation dosage as low as 0.5 microg of iron/mL of culture
      medium with 1.2x105 hMSCs, and the in vitro detection threshold of cell number is
      about 1x104 cells. Furthermore, 1.2x105 labeled cells can also be MRI-detected in
      a subcutaneous model in vivo. Labeled hMSCs are unaffected in their viability,
      proliferation, and differentiation capacities into adipocytes and osteocytes
      which can still be readily MRI detected. This is the first report that hMSCs can
      be efficiently labeled with MRI contrast nanoparticles and can be monitored in
      vitro and in vivo with a clinical 1.5-T MRI imager under low incubation
      concentration of iron oxide, short incubation time, and low detection cell
      numbers at the same time.

PMID- 17212456
TI  - Effects of mechanical flexion on the penetration of fullerene amino acid
      derivatized peptide nanoparticles through skin.
AB  - Dermatomed porcine skin was fixed to a flexing device and topically dosed with
      33.5 mg.mL-1 of an aqueous solution of a fullerene-substituted phenylalanine
      (Baa) derivative of a nuclear localization peptide sequence (Baa-Lys(FITC)-NLS).
      Skin was flexed for 60 or 90 min or left unflexed (control). Confocal microscopy
      depicted dermal penetration of the nanoparticles at 8 h in skin flexed for 60 and
      90 min, whereas Baa-Lys(FITC)-NLS did not penetrate into the dermis of unflexed
      skin until 24 h. TEM analysis revealed fullerene-peptide localization within the
      intercellular spaces of the stratum granulosum.

PMID- 17212457
TI  - Nanoscale cell adhesion ligand presentation regulates nonviral gene delivery and
      expression.
AB  - It is hypothesized that the nanoscale organization of cell adhesion ligands in a
      synthetic ECM regulates nonviral gene delivery. This hypothesis was examined with
      pre-osteoblasts cultured on substrates which present varied density and spacing
      of synthetic adhesion ligands. The levels of gene transfer and expression were
      increased with the density of adhesion ligands, but decreased with the spacing of
      ligands, due to changes in the cell growth rate. This study provides a material
      based control point on the nanometer scale for nonviral gene based therapies.

PMID- 17212458
TI  - Nanoblossoms: light-induced conformational changes of cationic polyelectrolyte
      stars in the presence of multivalent counterions.
AB  - We analyze the structure of star-shaped polyelectrolytes in the presence of di-
      and trivalent counterions, and we use the gained knowledge to manipulate the
      polyelectrolyte's conformation by light. By applying dynamic light scattering and
      atomic force microscopy, we demonstrate that, at constant ionic strength, the
      arms of the cationic polyelectrolyte retract when adding multivalent counterions.
      Adding trivalent hexacyanocobaltate(III) ions leads to a collapse of the
      polyelectrolyte star even at low concentrations. This is shown by analysis of the
      star polyelectrolytes in solution as well as in the adsorbed state on mica
      surfaces. Considerably higher salt concentrations are necessary to obtain the
      same contraction of the polyelectrolyte star if the divalent
      tetracyanonickelate(II) ions are used. Sufficiently high multivalent counterion
      concentration leads finally to the precipitation of the polymer from the
      solution. We demonstrate that we can switch a polyelectrolyte star from the
      collapsed to the expanded state by transforming the trivalent
      hexacyanocobaltate(III) ions into a mixture of mono- and divalent ions by UV
      light. Thus, these collapsed stars react to light like "nanoblossoms". Moreover,
      polyelectrolyte stars precipitated through addition of the trivalent
      hexacyanocobaltate(III) ions can be redissolved by irradiation with light
      (photoinduced dissolution). Hence, the conformation and interaction of star
      polyelectrolytes can be switched by light. Possible applications of this novel
      way of manipulating polymers are discussed.

PMID- 17212459
TI  - Cationic comb-type copolymers for boosting DNA-fueled nanomachines.
AB  - For the better applications and developments of DNA nanomachines, their
      responding kinetics, output, and sequence-selectivity need to be improved.
      Furthermore, the DNA nanomachines currently have several limitations in operating
      conditions. Here we show that a simple addition of a cationic comb-type
      copolymer, poly(l-lysine)-graft-dextran, produces the robust and quick responses
      of DNA nanomachines under moderate conditions including physiologically relevant
      conditions even at very low strand concentrations (nanomoles per liter range)
      through hybrid stabilization and DNA strand exchange acceleration.

PMID- 17212460
TI  - Semiconductor quantum rods as single molecule fluorescent biological labels.
AB  - In this paper, we report the development of rod-shaped semiconductor nanocrystals
      (quantum rods) as fluorescent biological labels. Water-soluble biocompatible
      quantum rods have been prepared by surface silanization and applied for
      nonspecific cell tracking as well as specific cellular targeting. Quantum rods
      are brighter single molecule probes as compared to quantum dots. They have many
      potential applications as biological labels in situations where their properties
      offer advantages over quantum dots.

PMID- 17212461
TI  - Instabilities in nanoporous media.
AB  - Rayleigh instabilities in thin polymer films confined within nanoporous alumina
      membranes were studied. Thin films of poly(methyl methacrylate) (PMMA) were
      prepared by filling cylindrical nanopores in an anodic aluminum oxide (AAO)
      membrane with a PMMA solution in chloroform followed by solvent evaporation. When
      the PMMA nanotubes were annealed above the glass transition temperature (Tg),
      undulations in the film thickness were observed that were induced by a Rayleigh
      instability. The amplitude of the undulations increased with time and eventually
      bridged across the cylindrical nanopore in the AAO membrane, resulting in the
      formation of polymer nanorods with periodic encapsulated holes. A similar
      behavior was observed when PMMA films were confined within carbon nanotubes
      (CNTs). The Rayleigh instabilities in these confined geometries offer a novel
      means of controlling and fabricating the polymer nanostructures. These
      compartmentalized nanorods may have potential applications as delivery devices.

PMID- 17212462
TI  - Enhancement of the luminescence intensity of InAs/GaAs quantum dots induced by an
      external electric field.
AB  - InAs/GaAs quantum dots have been subjected to a lateral external electric field
      in low-temperature microphotoluminescence measurements. It is demonstrated that
      the dot PL signal could be increased several times depending on the magnitude of
      the external field and the strength of the internal (built-in) electric field,
      which could be altered by an additional infrared illumination of the sample. The
      observed effects are explained by a model that accounts for the essentially
      faster lateral transport of the photoexcited carriers achieved in an electric
      field.

PMID- 17212463
TI  - Low-frequency noise in nanoscale ballistic transistors.
AB  - Low-frequency "1/f" noise is a major issue for nanoscale devices such at carbon
      nanotube transistors. We show that nanoscale ballistic transistors give voltage
      dependent sensitivity to the intrinsic potential fluctuations from nearby charge
      traps. A distinctive dependence on gate voltage is predicted, without reference
      to the number of carriers. This dependence is confirmed by comparison with recent
      measurements of nanotube transistors. Possible ways of decreasing the noise are
      discussed.

PMID- 17212464
TI  - Morphology control of layer-structured gallium selenide nanowires.
AB  - Layer-structured group III chalcogenides have highly anisotropic properties and
      are attractive materials for stable photocathodes and battery electrodes. We
      report the controlled synthesis and characterization of layer-structured GaSe
      nanowires via a catalyst-assisted vapor-liquid-solid (VLS) growth mechanism
      during GaSe powder evaporation. GaSe nanowires consist of Se-Ga-Ga-Se layers
      stacked together via van der Waals interactions to form belt-shaped nanowires
      with a growth direction along the [11-20], width along the [1-100], and height
      along the [0001] direction. Nanobelts exhibit a variety of morphologies including
      straight, zigzag, and saw-tooth shapes. These morphologies are realized by
      controlling the growth temperature and time so that the actual catalysts have a
      chemical composition of Au, Au-Ga alloy, or Ga. The participation of Ga in the
      VLS catalyst is important for achieving different morphologies of GaSe. In
      addition, GaSe nanotubes are also prepared by a slow growth process.

PMID- 17212465
TI  - Ballistic transport in graphene nanostrips in the presence of disorder:
      importance of edge effects.
AB  - Stimulated by recent advances in isolating graphene and similarities to single
      wall carbon nanotubes, simulations were performed to assess the effects of static
      disorder on the conductance of metallic armchair- and zigzag-edge graphene
      nanostrips. Both strip types were found to have outstanding ballistic transport
      properties in the presence of a substrate-induced disorder. However, only the
      zigzag-edge strips retain these properties in the presence of irregular edges,
      making them better initial synthetic targets for ballistic device applications.

PMID- 17212466
TI  - Active alignment of microtubules with electric fields.
AB  - The direction of translocation of microtubules on a surface coated with kinesin
      is usually random. Here we demonstrate and quantify the rate at which externally
      applied electric fields can direct moving microtubules parallel to the field by
      deflecting their leading end toward the anode. Effects of electric field
      strength, kinesin surface density, and microtubule translocation speed on the
      rate of redirection of microtubules were analyzed statistically. Furthermore, we
      demonstrated that microtubules can be steered in any desired direction via
      manipulation of externally applied E-fields.

PMID- 17212467
TI  - Intermediate-band solar cells employing quantum dots embedded in an energy fence
      barrier.
AB  - Power efficiencies>60% have been predicted for idealized quantum dot (QD)
      intermediate band solar cells. This goal has not yet been realized, due in part
      to nonidealities that result in charge trapping followed by recombination of
      photocarriers in the QDs, and the lack of an optimal materials combination. To
      eliminate charge trapping, a p+-i-n+ cell employing QDs buried within a high band
      gap barrier layer is proposed and analyzed. The maximum solar power conversion
      efficiency under AM1.5 spectral radiation of an example GaAs-based photovoltaic
      cell employing 10-20 layers of InAs QDs surrounded by AlxGa1-xAs barriers in the
      junction built-in depletion region can be as high as 45%. Higher efficiencies are
      anticipated for InP-based cells. This represents a significant improvement over
      GaAs homojunction cells with maximum efficiencies of <25%.

PMID- 17212469
TI  - Development of the chemistry of indium in formal oxidation States lower than +3.

PMID- 17212470
TI  - Metal-free methods in the synthesis of macrocyclic schiff bases.

PMID- 17212471
TI  - Structures and oxide mobility in Bi-Ln-O materials: heritage of Bi2O3.

PMID- 17212472
TI  - Alternative roles for metal ions in enzyme catalysis and the implications for
      ribozyme chemistry.

PMID- 17212474
TI  - Carbon-carbon coupling reactions catalyzed by heterogeneous palladium catalysts.

PMID- 17212473
TI  - Natural and synthetic fluoride carbonates.

PMID- 17212475
TI  - Aryl-aryl bond formation by transition-metal-catalyzed direct arylation.

PMID- 17212476
TI  - Total synthesis of natural 8- and 9-membered lactones: recent advancements in
      medium-sized ring formation.

PMID- 17212477
TI  - Recent progress in development of dopamine receptor subtype-selective agents:
      potential therapeutics for neurological and psychiatric disorders.

PMID- 17212480
TI  - Diarylethene microcrystals make directional jumps upon ultraviolet irradiation.
AB  - Microcrystals of a diarylethene {1,2-bis[5'-methyl-2'-(2"
      pyridyl)thiazolyl]perfluorocyclo-pentene} undergo jumps upon photoirradiation.
      These photochromic crystals present molecular structural changes upon irradiation
      with ultraviolet light because of reversible photocyclization reactions. When the
      energy absorbed by crystals reaches about 10 microJ, the uniaxial stress induced
      in the crystal lattice relaxes through directional jumps. If one prevents
      crystals from jumping, then parallel, equidistant cracks appear on crystal
      surfaces. These photomechanical effects could result from a Grinfeld surface
      instability.

PMID- 17212481
TI  - The nature of the [20.0] 1Sigma+ electronic state of RhB: a multiconfigurational
      study.
AB  - Multiconfigurational second order perturbation theory, with extended atomic basis
      sets and inclusion of scalar relativistic effects, was employed to investigate
      the low-lying (1)Sigma(+) electronic states of RhB. The [20.0] (1)Sigma(+) state
      is represented by a single configuration, mid R:[ellipsis
      (horizontal)]10sigma(2)11sigma(1)5pi(4)2delta(4)12sigma(1), derived from a single
      excitation (11sigma-->12sigma) from the ground state, which defines its
      electronic nature. A new excited state, coined as [9.0] (1)Delta (R(0)=1.786A,
      DeltaG(12)=792 cm(-1)), located 9221 cm(-1) above the X(1)Sigma(+) state, and
      described by the |...10sigma(2)11sigma(2)5pi(4)2delta(3)12sigma(1)> electronic
      configuration, was also identified.

PMID- 17212482
TI  - A thermochemically competitive local hybrid functional without gradient
      corrections.
AB  - Following the suggestion of local hybrid functionals with position-dependent
      exact-exchange admixture [J. Jaramillo, G. E. Scuseria, and M. Ernzerhof, J.
      Chem. Phys. 118, 1068 (2003)], a functional that mixes only local and exact
      exchange plus local correlation has been constructed. With a simple local mixing
      function for the position dependence, this Lh-SVWN functional provides
      atomization energies for the G2-1 set that are competitive with currently
      available state-of-the-art functionals like, e.g., B3LYP. This is achieved
      without generalized gradient approximations for exchange or correlation.

PMID- 17212483
TI  - One photon two electron excitations between doubly excited states of helium.
AB  - Variational calculations using Hylleraas coordinates have been performed for the
      first time for estimating the energies of 3dnf((1,3)D(o)) state of helium for
      n=4,5,6. We predict absorption peaks at 12.219, 12.647, and 12.857 eV for the
      (3)D(o) series converging to N=3 ionization threshold of He(+) which can be
      expected to be observed in the experiment of single photon double excitation of
      lowest (3)P(e) state of helium placed in synchrotron radiation.

PMID- 17212484
TI  - Canonical sampling through velocity rescaling.
AB  - The authors present a new molecular dynamics algorithm for sampling the canonical
      distribution. In this approach the velocities of all the particles are rescaled
      by a properly chosen random factor. The algorithm is formally justified and it is
      shown that, in spite of its stochastic nature, a quantity can still be defined
      that remains constant during the evolution. In numerical applications this
      quantity can be used to measure the accuracy of the sampling. The authors
      illustrate the properties of this new method on Lennard-Jones and TIP4P water
      models in the solid and liquid phases. Its performance is excellent and largely
      independent of the thermostat parameter also with regard to the dynamic
      properties.

PMID- 17212485
TI  - Estimation of absolute solvent and solvation shell entropies via permutation
      reduction.
AB  - Despite its prominent contribution to the free energy of solvated macromolecules
      such as proteins or DNA, and although principally contained within molecular
      dynamics simulations, the entropy of the solvation shell is inaccessible to
      straightforward application of established entropy estimation methods. The
      complication is twofold. First, the configurational space density of such systems
      is too complex for a sufficiently accurate fit. Second, and in contrast to the
      internal macromolecular dynamics, the configurational space volume explored by
      the diffusive motion of the solvent molecules is too large to be exhaustively
      sampled by current simulation techniques. Here, we develop a method to overcome
      the second problem and to significantly alleviate the first one. We propose to
      exploit the permutation symmetry of the solvent by transforming the trajectory in
      a way that renders established estimation methods applicable, such as the
      quasiharmonic approximation or principal component analysis. Our permutation
      reduced approach involves a combinatorial problem, which is solved through its
      equivalence with the linear assignment problem, for which O(N3) methods exist.
      From test simulations of dense Lennard-Jones gases, enhanced convergence and
      improved entropy estimates are obtained. Moreover, our approach renders diffusive
      systems accessible to improved fit functions.

PMID- 17212486
TI  - Performance of density functionals for first row transition metal systems.
AB  - This article investigates the performance of five commonly used density
      functionals, B3LYP, BP86, PBE0, PBE, and BLYP, for studying diatomic molecules
      consisting of a first row transition metal bonded to H, F, Cl, Br, N, C, O, or S.
      Results have been compared with experiment wherever possible. Open-shell
      configurations are found more often in the order PBE0>B3LYP>PBE approximately
      BP86>BLYP. However, on average, 58 of 63 spins are correctly predicted by any
      functional, with only small differences. BP86 and PBE are slightly better for
      obtaining geometries, with errors of only 0.020 A. Hybrid functionals tend to
      overestimate bond lengths by a few picometers and underestimate bond strengths by
      favoring open shells. Nonhybrid functionals usually overestimate bond energies.
      All functionals exhibit similar errors in bond energies, between 42 and 53 kJmol.
      Late transition metals are found to be better modeled by hybrid functionals,
      whereas nonhybrid functionals tend to have less of a preference. There are
      systematic errors in predicting certain properties that could be remedied. BLYP
      performs the best for ionization potentials studied here, PBE0 the worst. In
      other cases, errors are similar. Finally, there is a clear tendency for hybrid
      functionals to give larger dipole moments than nonhybrid functionals. These
      observations may be helpful in choosing and improving existing functionals for
      tasks involving transition metals, and for designing new, improved functionals.

PMID- 17212487
TI  - Model colloidal fluid with competing interactions: bulk and interfacial
      properties.
AB  - Using a simple mean field density functional theory (DFT), the authors
      investigate the structure and phase behavior of a model colloidal fluid composed
      of particles interacting via a pair potential which has a hard core of diameter
      sigma, is attractive Yukawa at intermediate separations, and is repulsive Yukawa
      at large separations. The authors analyze the form of the asymptotic decay of the
      bulk fluid correlation functions, comparing results from DFT with those from the
      self-consistent Ornstein-Zernike approximation (SCOZA). In both theories the
      authors find rich crossover behavior, whereby the ultimate decay of correlation
      functions changes from monotonic to long wavelength damped oscillatory decay on
      crossing certain lines in the phase diagram or sometimes from oscillatory to
      oscillatory with a longer wavelength. For some choices of potential parameters
      the authors find, within the DFT, a lambda line at which the fluid becomes
      unstable with respect to periodic density fluctuations. SCOZA fails to yield
      solutions for state points near such a lambda line. The propensity towards
      clustering of particles, which is reflected by the presence of a long wavelength
      (>>sigma) slowly decaying oscillatory pair correlation function, and a structure
      factor that exhibits a very sharp maximum at small but nonzero wave numbers, is
      enhanced in states near the lambda line. The authors present density profiles for
      the planar liquid-gas interface and for fluids adsorbed at a planar hard wall.
      The presence of a nearby lambda transition gives rise to pronounced long
      wavelength oscillations in the one-body density profiles at both types of
      interface.

PMID- 17212488
TI  - Assessment of the exchange-correlation functionals for the physical description
      of spin transition phenomena by density functional theory methods: all the same?
AB  - This study aims to assess present day density functionals in the description of
      spin crossover iron(II) complexes. Two recently synthesized spin crossover
      complexes were considered. Theoretical calculations were made using 53 of the
      most popular exchange-correlation density functionals with triple zeta plus
      polarization quality basis sets. The present work shows that even though
      different density functionals can lead to different energy gaps between spin
      states, most of them are very similar for these two compounds when a comparison
      between energy gaps is sought. The present work shows that even though different
      exchange correlations can lead to different energy gaps between spin states, the
      difference between these gaps calculated at different geometries and that
      calculated at a given reference geometry is surprisingly independent of the
      choice of functional. The reasons for the similarities and the differences among
      exchange and correlation functional combinations are discussed.

PMID- 17212489
TI  - Do intense electromagnetic fields annihilate/create conical intersections?
AB  - In this article the authors relate the possibility that an intense electric field
      affects topological features of a molecular system. For this purpose they studied
      a model based on the Mathieu equation. They found that such a field may affect
      the spatial distribution of the nonadiabatic coupling terms but not the position
      of the intersections. In other words an intense electric field does not create or
      annihilate conical intersections. It is shown that this conclusion is valid as
      long as the field is an analytic function of the coordinates in the region of
      interest. These findings can be extended to magnetic fields (or electromagnetic
      fields) as long as they are analytic functions in the region of interest.

PMID- 17212490
TI  - Polarizability and second hyperpolarizability evaluation of long molecules by the
      density functional theory with long-range correction.
AB  - Polarizabilities and second hyperpolarizabilities of polyacetylene and a hydrogen
      chain are evaluated by density functional theory (DFT) using a hybrid generalized
      gradient approximation functional with correct long-range electron-electron
      interactions. The well known catastrophic overestimate of the
      hyperpolarizabilities for molecular systems of enhanced length is corrected by
      the two-electron repulsion operator decomposition technique, integrating the
      distance-dependent nonlocal exchange effects for long-range interaction, while
      neither the asymptotically corrected exchange functional for long-range
      interaction nor ordinary hybrid methods seem to be capable of overcoming the
      serious drawback of the DFT in polarizability/hyperpolarizability evaluation.

PMID- 17212491
TI  - New implementation of second-order Moller-Plesset perturbation theory with an
      analytic Slater-type geminal.
AB  - The author introduces a new method for the exchange commutator integrals in
      explicitly correlated Moller-Plesset second order perturbation theory. The method
      is well suited with an analytic Slater-type geminal correlation factor. He also
      explains the scheme for auxiliary integrals needed for the correlation factor.
      Based on different Ansatze, he analyzes the performance of the method on
      correlation energies and reaction enthalpies in detail.

PMID- 17212492
TI  - Relativistic coupled-cluster calculations of parity nonconservation in Ba+ by the
      sum-over-states approach.
AB  - The authors present the results of their calculation for the parity nonconserving
      5p(6)6s(1/2)-->5p(6)5d(3/2) transition in Ba+ using the relativistic coupled
      cluster theory in the singles, doubles, and partial triples approximation. The
      contributions from the leading intermediate states are explicitly considered. It
      is found that the largest contribution comes from the |5p(6)6p(1/2)> state. Their
      results are in reasonable agreement with other calculations.

PMID- 17212493
TI  - Hard-wall potential function for transport properties of alkali metal vapors.
AB  - This study demonstrates that the transport properties of alkali metals are
      determined principally by the repulsive wall of the pair interaction potential
      function. The (hard-wall) Lennard-Jones (LJ) (15-6) effective pair potential
      function is used to calculate the transport collision integrals. Accordingly,
      reduced collision integrals of K, Rb, and Cs metal vapors are obtained from the
      Chapman-Enskog solution of the Boltzmann equation. The law of corresponding
      states based on the experimental transport reduced collision integral is used to
      verify the validity of a LJ(15-6) hybrid potential in describing the transport
      properties. LJ(8.5-4) potential function and a simple thermodynamic argument with
      the input PVT data of liquid metals provide the required molecular potential
      parameters. Values of the predicted viscosity of monatomic alkali metal vapor are
      in agreement with typical experimental data with average absolute deviations of
      2.97% for K in the range of 700-1500 K, 1.69% for Rb, and 1.75% for Cs in the
      range of 700-2000 K. In the same way, the values of predicted thermal
      conductivity are in agreement with experiment within 2.78%, 3.25%, and 3.63% for
      K, Rb, and Cs, respectively. The LJ(15-6) hybrid potential with a hard-wall
      repulsion character conclusively predicts the best transport properties of the
      three alkali metal vapors.

PMID- 17212494
TI  - Liquid-vapor transition of systems with mean field universality class.
AB  - We have considered a system where the interaction, v(r)=v(IS)(r)+xi(2)v(MF)(r),
      is given as a linear combination of two potentials, each of which being
      characterized with a well-defined critical behavior: for v(IS)(r) we have chosen
      the potential of the restricted primitive model which is known to belong to the
      three-dimensional Ising universality class, while for v(MF)(r) we have considered
      a long-range interaction in the Kac [J. Math. Phys. 4, 216 (1963)] limit,
      displaying mean field (MF) behavior. We study the performance of two theoretical
      approaches and of computer simulations in the critical region for this particular
      system and give a detailed comparison between theories and simulation of the
      critical region and the location of the critical point. Having shown by
      theoretical arguments that the system belongs to the MF universality class for
      any positive value of xi and shows nonclassical behavior only for xi=0, we
      examine to which extent theoretical approximations and simulation can reproduce
      this behavior. While in this limiting case theoretical approaches are known to
      fail, we find good agreement for the critical properties between the theoretical
      approaches and the simulations for xi(2) larger than 0.05.

PMID- 17212495
TI  - Theoretical approach to evaluate thermodiffusion in aqueous alkanol solutions.
AB  - Flow due to thermodiffusion may change direction in fluid mixtures with the
      variation of composition and temperature. This occurrence remains an unraveled
      phenomenon in petroleum research. Using a modified theoretical approach, this
      paper evaluates the thermal diffusion factor in alkanol water mixtures, including
      methanol, ethanol, and isopropanol aqueous mixtures. By combining this approach
      with an equation of state perturbed chain statistical associating fluid theory
      and using two adjustable parameters calculated from experimental data, the
      present approach provides a good agreement for the prediction of thermal
      diffusion in alkanol water mixtures when compared with the available experimental
      data. This work reveals that the thermodiffusion in infinite dilutions may play
      an important role in understanding the thermodiffusion phenomena.

PMID- 17212496
TI  - The Ehrenfest method with quantum corrections to simulate the relaxation of
      molecules in solution: equilibrium and dynamics.
AB  - The use of the Ehrenfest method to simulate the relaxation of molecules in
      solution is explored. Using the cyanide ion dissolved in water as a test model,
      the independent trajectory (IT) and the bundle of trajectories (BT)
      approximations are shown to provide very different results for the time evolution
      of the vibrational populations of the solute. None of these approximations
      reproduce the Boltzmann equilibrium vibrational populations accurately. A
      modification of the Ehrenfest method based on the use of quantum correction
      factors is thus proposed to solve this problem. The simulations carried out using
      the modified Ehrenfest method provide IT and BT relaxation times which are closer
      to each other and which agree quite well with previous hybrid perturbative
      results.

PMID- 17212497
TI  - Study of water dynamics and distances in paramagnetic solids by variable
      temperature two-dimensional 2H NMR spectroscopy.
AB  - A recently proposed two-dimensional (2)H NMR experiment is used to measure the
      (2)H (spin I=1) quadrupolar and paramagnetic shift anisotropy interactions in
      powdered CuCl(2).2D(2)O as a function of temperature. The principal components of
      the quadrupolar and paramagnetic shift anisotropy tensors and the Euler angles
      describing the orientations of the tensors in the molecular frame are determined
      at each temperature. For this purpose an analytical approach is introduced to
      extract desired parameters from motionally averaged two-dimensional line shapes
      where the averaging is introduced by rapid 180 degrees flips around C(2) axes of
      D(2)O molecules. This approach can be readily applied to study various materials
      containing water of crystallization. It is also clearly shown that the rapid
      continuous rotation of D(2)O molecules around their C(2) axes is not taking place
      in the studied solid in the range of temperatures between 209 and 344 K. Once the
      paramagnetic shift anisotropy of a deuterium atom is measured accurately it is
      used to estimate the distance between deuterium and the nearest copper atom
      bearing an unpaired electron. Excellent agreement is found between structural
      parameters obtained in this study and those provided by neutron and x-ray
      diffraction, showing that the paramagnetic shift anisotropy is a sensitive probe
      of distances in paramagnetic solids.

PMID- 17212498
TI  - Ideal glass transitions, shear modulus, activated dynamics, and yielding in
      fluids of nonspherical objects.
AB  - An extension of naive ideal mode coupling theory (MCT) and its generalization to
      treat activated barrier hopping and glassy dynamics in fluids and suspensions
      composed of nonspherical hard core objects is proposed. An effective center-of
      mass description is adopted. It corresponds to a specific type of pre-averaging
      of the dynamical consequences of orientational degrees of freedom. The simplest
      case of particles composed of symmetry-equivalent interaction sites is
      considered. The theory is implemented for a homonuclear diatomic shape of
      variable bond length. The naive MCT glass transition boundary is predicted to be
      a nonmonotonic function of the length-to-width or aspect ratio and occurs at a
      nearly unique value of the dimensionless compressibility. The latter quantifies
      the amplitude of long wavelength thermal density fluctuations, thereby
      (empirically) suggesting a tight connection between the onset of localization and
      thermodynamics. Localization lengths and elastic shear moduli for different
      aspect ratio and volume fraction systems approximately collapse onto master
      curves based on a reduced volume fraction variable that quantifies the distance
      from the ideal glass transition. Calculations of the entropic barrier height and
      hopping time, maximum restoring force, and absolute yield stress and strain as a
      function of diatomic aspect ratio and volume fraction have been performed. Strong
      correlations of these properties with the dimensionless compressibility are also
      found, and nearly universal dependences have been numerically identified based on
      property-specific nondimensionalizations. Generalization of the approach to rigid
      rods, disks, and variable shaped molecules is possible, including oriented liquid
      crystalline phases.

PMID- 17212499
TI  - Photoionization affected by chemical anisotropy.
AB  - The kinetic constants of rhodamine 3B quenching by N,N-dimethyl aniline were
      extracted from the very beginning of the quenching kinetics, recently studied in
      a few solvents of different viscosities. They were well fitted with the
      conventional kinetic constant definition, provided the radial distribution
      function of simple liquids was ascribed to the reactant pair distribution and the
      contact electron transfer rate was different in all the cases. This difference
      was attributed to the chemical anisotropy averaging by the rotation of reactants,
      which is the faster in solvents of lower viscosity. With the proper choice of a
      space dependent encounter diffusion, the whole quenching kinetics was well fitted
      with an encounter theory, using the Marcus [J. Chem. Phys. 24, 966 (1956); 43,
      679 (1965)] transfer rate instead of the contact Collins-Kimball [J. Colloid.
      Sci. 4, 425 (1949)] approximation. Not only the beginning and middle part of the
      quenching were equally well fitted, but the long time (Markovian) rate constant
      was also found to be the same as previously obtained. Moreover, the concentration
      dependencies of the fluorescence quantum yield and the Stern-Volmer constant were
      specified and await their experimental verification.

PMID- 17212500
TI  - Solubility of KF and NaCl in water by molecular simulation.
AB  - The solubility of two ionic salts, namely, KF and NaCl, in water has been
      calculated by Monte Carlo molecular simulation. Water has been modeled with the
      extended simple point charge model (SPC/E), ions with the Tosi-Fumi model and the
      interaction between water and ions with the Smith-Dang model. The chemical
      potential of the solute in the solution has been computed as the derivative of
      the total free energy with respect to the number of solute particles. The
      chemical potential of the solute in the solid phase has been calculated by
      thermodynamic integration to an Einstein crystal. The solubility of the salt has
      been calculated as the concentration at which the chemical potential of the salt
      in the solution becomes identical to that of the pure solid. The methodology used
      in this work has been tested by reproducing the results for the solubility of KF
      determined previously by Ferrario et al. [J. Chem. Phys. 117, 4947 (2002)]. For
      KF, it was found that the solubility of the model is only in qualitative
      agreement with experiment. The variation of the solubility with temperature for
      KF has also been studied. For NaCl, the potential model used predicts a
      solubility in good agreement with the experimental value. The same is true for
      the hydration chemical potential at infinite dilution. Given the practical
      importance of solutions of NaCl in water the model used in this work, whereas
      simple, can be of interest for future studies.

PMID- 17212501
TI  - Isotropic Brillouin spectra of liquids having an internal degree of freedom.
AB  - Isotropic Brillouin spectra of the two chemically similar van der Waals glass
      forming liquids, 1,1(')-di(4-methoxy-5-methylphenyl)cyclohexane (BMMPC) and
      1,1(')-bis(p-methoxy-phenyl)cyclohexane (BMPC) and ortho-terphenyl (OTP), were
      studied in a broad temperature and pressure range in order to characterize the
      effect of internal relaxations on the damping of longitudinal phonons. Such
      relaxations are present in BMPC, while in BMMPC and OTP they are strongly
      hindered. The authors show that in BMPC (with strong internal relaxations) the
      damping (broadening) of longitudinal phonons (Brillouin peaks) is much stronger
      than in BMMPC and OTP (with weaker internal relaxations). The contributions of
      the internal and structural relaxations to the phonon damping can be separated
      using high pressure, due to their very different pressure dependences. They show
      that internal relaxations strongly contribute to the damping of longitudinal
      phonons at all temperatures and should be taken into account in theoretical
      models describing the Brillouin spectra of supercooled liquids.

PMID- 17212502
TI  - Electronically excited water aggregates and the adiabatic band gap of water.
AB  - The authors report results for the electronic properties of the S(1) singlet
      excited state of H(3)O(+)[OH(H(2)O)((n-2))](-) aggregates, where n=2-5 is the
      number of water molecules. The energy of the excited state was defined relative
      to the ground state of neutral water clusters. Results for ionized aggregates are
      also reported. The results are based on configuration interaction with single
      excitations geometry optimizations followed by density functional theory and time
      dependent density functional theory calculations. Emphasis was placed on the
      relationship between electronic properties of the aggregates and the adiabatic
      band gap of liquid water. The authors' predictions for the adiabatic energy gap
      of water clusters are in the 6.01-6.55 eV range. These values are approximately
      0.9-0.4 eV below the experimental adiabatic band gap of liquid water (6.9 eV).
      Comparison with experimental information for water is reported for several
      properties of interest including vertical and adiabatic ionization energies,
      excitation energies, photoemission thresholds, and conduction band edge. The
      results provide a description, at the molecular level, for the electronic
      properties of water aggregates that is consistent with the current picture for
      the band gap of bulk water [J. V. Coe, Int. Rev. Phys. Chem. 20, 33 (2001)].

PMID- 17212503
TI  - Exploring conformational energy landscape of glassy disaccharides by cross
      polarization magic angle spinning 13C NMR and numerical simulations. I.
      Methodological aspects.
AB  - This article demonstrates the ability of chemical shift surfaces to provide
      information on distributions of various conformations of disaccharides in the
      glassy, solid state. The validity of the general method leading to a simulation
      of inhomogeneous (13)C chemical shift distributions is discussed in detail. In
      particular, a proper consideration of extrema and saddle points of the chemical
      shift map correctly accounts for the observed discontinuities in the experimental
      cross polarization magic angle spinning spectra. Provided that these basic
      requirements are met, density functional theory/gauge-independent atomic orbital
      chemical shift maps calculated on relaxed conformations lead to a very
      satisfactory description of the experimental line shapes. Using amorphous
      trehalose as a model disaccharide, the simulation unambiguously defines the range
      of most populated conformations in the glass.

PMID- 17212504
TI  - Exploring the conformational energy landscape of glassy disaccharides by cross
      polarization magic angle spinning 13C nuclear magnetic resonance and numerical
      simulations. II. Enhanced molecular flexibility in amorphous trehalose.
AB  - This paper uses chemical shift surfaces to simulate experimental (13)C cross
      polarization magic angle spinning spectra for amorphous solid state
      disaccharides, paying particular attention to the glycosidic linkage atoms in
      trehalose, sucrose, and lactose. The combination of molecular mechanics with
      density functional theory/gauge invariant atomic orbital ab initio methods
      provides reliable structural information on the conformational distribution in
      the glass. The results are interpreted in terms of an enhanced flexibility that
      trehalose possesses in the amorphous solid state, at least on the time scale of
      (13)C nuclear magnetic resonance measurements. Implications of these findings for
      the fragility of trehalose glass and bioprotectant action are discussed.

PMID- 17212505
TI  - 2H nuclear magnetic resonance study on the molecular motion in cyanoadamantane.
      II. Orientationally ordered and glassy crystalline phase.
AB  - The orientationally ordered crystalline and glassy plastically crystalline phase
      of cyanoadamantane were investigated using (2)H NMR. Solid-echo line shape, two
      dimensional spectrum, and spin-lattice relaxation were analyzed. In both phases,
      the molecules display solely a rotation around the molecular C(3) symmetry axis.
      For the orientationally ordered phase, a single correlation time characterizes
      the motion, and the time constant shows an Arrhenius temperature dependence. In
      contrast, a broad distribution G[ln(tau)] of correlation times is observed for
      the glassy plastically crystalline phase that leads to characteristically
      different NMR features such as "two-phase" spectra and pronounced nonexponential
      relaxation. The distribution G[ln(tau)] can be derived from a temperature
      independent distribution of activation energies g(E(a)), with its mean value
      lying significantly below the activation energy corresponding to the ordered
      phase. Thus, the molecular uniaxial rotation proves to be a sensitive probe for
      the energy landscape of the orientationally disordered glassy crystalline phase
      of cyanoadamantane.

PMID- 17212506
TI  - The renormalized jellium model for spherical and cylindrical colloids.
AB  - Starting from a mean-field description for a dispersion of highly charged
      spherical or (parallel) rodlike colloids, we introduce the simplification of a
      homogeneous background to include the contribution of other polyions to the
      static field created by a tagged polyion. The charge of this background is self
      consistently renormalized to coincide with the polyion effective charge, the
      latter quantity thereby exhibiting a nontrivial density dependence, which
      directly enters into the equation of state through a simple analytical
      expression. The good agreement observed between the pressures calculated using
      the renormalized jellium and Monte Carlo simulations confirms the relevance of
      the renormalized jellium model for theoretical and experimental purposes and
      provides an alternative to the Poisson-Boltzmann cell model since it is free of
      some of the intrinsic limitations of this approach.

PMID- 17212507
TI  - Structural and electronic properties of Al12X+ (X=C, Si, Ge, Sn, and Pb)
      clusters.
AB  - Using the first-principles method with the generalized gradient approximation,
      the authors have studied the structural and electronic properties of Al(12)X(+)
      (X=C, Si, Ge, Sn, and Pb) clusters in detail. The ground state of Al(12)C(+) is a
      low symmetry C(s) structure instead of an icosahedron. However, the Si, Ge, Sn,
      and Pb atom doped cationic clusters favor icosahedral structures. The ground
      states for Al(12)Si(+) and Al(12)Ge(+) are icosahedra, while the C(5nu)
      structures optimized from an icosahedron with a vertex capped by a tetravalent
      atom have the highest binding energy for Al(12)Sn(+) and Al(12)Pb(+) clusters.
      The I(h) structure and the C(5nu) structure are almost degenerate for
      Al(12)Ge(+), whose binding energy difference is only 0.03 eV. The electronic
      properties are altered much by removing an electron from the neutral cluster. The
      binding strength of a valence electron is enhanced, while the binding energy of
      the cluster is reduced much. Due to the open electronic shell, the band gaps
      between the highest occupied molecular orbital and the lowest unoccupied
      molecular orbital are approximately 0.3 eV for the studied cationic clusters.

PMID- 17212508
TI  - Density functional investigation of the interaction of acetone with small gold
      clusters.
AB  - The structural evolution of Au(n) (n=2, 3, 5, 7, 9, and 13) clusters and the
      adsorption of organic molecules such as acetone, acetaldehyde, and diethyl ketone
      on these clusters are studied using a density functional method. The detailed
      study of the adsorption of acetone on the Au(n) clusters reveals two main points.
      (1) The acetone molecule interacts with one gold atom of the gold clusters via
      the carbonyl oxygen. (2) This interaction is mediated through back donation
      mainly from the spd-hybridized orbitals of the interacting gold atom to the
      oxygen atom of the acetone molecule. In addition, a hydrogen bond is observed
      between a hydrogen atom of the methyl group and another gold atom (not involved
      in the bonding with carbonyl oxygen). Interestingly, the authors notice that the
      geometries of Au(9) and Au(13) undergo a significant flattening due to the
      adsorption of an acetone molecule. They have also investigated the role of the
      alkyl chain attached to the carbonyl group in the adsorption process by analyzing
      the interaction of Au(13) with acetaldehyde and diethyl ketone.

PMID- 17212509
TI  - Properties of phase-coherent energy shuttling on the nanoscale.
AB  - Recently, the possibility of transporting electromagnetic energy as local-plasmon
      polariton waves along arrays of silver nanoparticles was demonstrated
      experimentally [S. A. Maier et al., Nat. Mater. 2, 229 (2003)]. It was shown that
      dipole coupling facilitates phase-coherent excitation waves, which propagate
      while competing against decoherence effects occurring within each dot. In this
      article the authors study the ideal coherent shuttling in such a system, leaving
      decoherence for future investigation. In the weak field limit, the waves obey a
      Schrodinger equation, to be solved using either time-dependent wave-packet or
      energy resolved scattering techniques. The authors study some dynamical
      characteristics of these waves, emphasizing intuition and insight. Scattering
      from barriers, longitudinal-transverse coupling and acceleration methods are
      studied in detail. The authors also discuss briefly two-dimensional arrays and a
      simple decoherence model.

PMID- 17212510
TI  - Aggregation of beta-amyloid fragments.
AB  - The authors study the folding and aggregation of six chains of the beta-amyloid
      fragment 16-22 using Monte Carlo simulations. While the isolated fragment prefers
      a helical form at room temperature, in the system of six interacting fragments
      one observes both parallel and antiparallel beta sheets below a crossover
      temperature T(x) approximately equal to 420 K. The antiparallel sheets have lower
      energy and are therefore more stable. Above the nucleation temperature the
      aggregate quickly dissolves into widely separated, weakly interacting chains.

PMID- 17212511
TI  - Hypersonic acoustic excitations in binary colloidal crystals: big versus small
      hard sphere control.
AB  - The phononic band structure of two binary colloidal crystals, at hypersonic
      frequencies, is studied by means of Brillouin light scattering and analyzed in
      conjunction with corresponding dispersion diagrams of the single colloidal
      crystals of the constituent particles. Besides the acoustic band of the average
      medium, the authors' results show the existence of narrow bands originating from
      resonant multipole modes of the individual particles as well as Bragg-type modes
      due to the (short-range) periodicity. Strong interaction, leading to the
      occurrence of hybridization gaps, is observed between the acoustic band and the
      band of quadrupole modes of the particles that occupy the largest fractional
      volume of the mixed crystal; the effective radius is either that of the large (in
      the symmetric NaCl-type crystalline phase) or the small (in the asymmetric
      NaZn(13)-type crystalline phase) particles. The possibility to reveal a universal
      behavior of the phononic band structure for different single and binary colloidal
      crystalline suspensions, by representing in the dispersion diagrams reduced
      quantities using an appropriate length scale, is discussed.

PMID- 17212512
TI  - Quantum surface diffusion of vibrationally excited molecular dimers.
AB  - We consider the thermally activated quantum diffusion of a molecular dimer in a
      periodic surface potential by means of a time-dependent wave packet method. We
      show that the potential energy surface resulting from the interplay of intradimer
      and dimer-surface interactions can lead to resonant states and predict high
      tunneling probabilities at specific, below barrier, energies that depend also on
      the initial vibrational state of the dimer. For soft molecular bonds, we show
      that the chaotic dynamical regime of classical dimers is mirrored, in the quantum
      case, by the tunneling induced mixing of vibrational states. The knowledge of the
      transmission coefficient is used to formulate an approximate description of
      quantum thermal diffusion by defining an effective temperature-dependent
      activation energy that can be compared to the classical case.

PMID- 17212513
TI  - Structure of polyelectrolyte complexes by Brownian dynamics simulation: effects
      of the bond length asymmetry of the polyelectrolytes.
AB  - Brownian dynamics simulations were performed to study the structure of
      polyelectrolyte complexes formed by two flexible, oppositely charged
      polyelectrolyte chains. The distribution of monomers in the complex as well as
      the radius of gyration and structure factor of complexes and individual
      polyelectrolytes are reported. These structural properties were calculated for
      polyelectrolyte chains with equal number of monomers, keeping constant the bond
      length of the negative chain and increasing the bond length of the positive
      chain. This introduces an asymmetry in the length of the chains that modulates
      the final structure of the complexes. In the symmetric case the distribution of
      positive and negative monomers in the complex are identical, producing clusters
      that are locally and globally neutral. Deviations from the symmetric case lead to
      nonuniform, asymmetric monomer distributions, producing net charge oscillations
      inside the complex and large changes in the radius of gyration of the complex and
      individual chains. From the radius of gyration of the polyelectrolyte chains it
      is shown that the positive chain is much more folded than the negative chain when
      the chains are asymmetric, which is also confirmed through the scaling behavior
      of the structure factors.

PMID- 17212514
TI  - Steric stabilization of spherical colloidal particles: Implicit and explicit
      solvent.
AB  - We present the results of Monte Carlo simulations and density functional theory
      treatment of interactions between spherical colloidal brushes both in implicit
      (good) solvent and in an explicit polymeric solution. Overall, theory is seen to
      be in good agreement with simulations. We find that interactions between hard
      sphere particles grafted with hard-sphere chains are always repulsive in implicit
      solvent. The range and steepness of the repulsive interaction is sensitive to the
      grafting density and the length of the grafted chains. When the brushes are
      immersed in an explicit solvent of hard-sphere chains, a weak mid-range
      attraction arises, provided the length of the free chains exceeds that of the
      grafted chains.

PMID- 17212515
TI  - Convergence and sampling efficiency in replica exchange simulations of peptide
      folding in explicit solvent.
AB  - Replica exchange methods (REMs) are increasingly used to improve sampling in
      molecular dynamics (MD) simulations of biomolecular systems. However, despite
      having been shown to be very effective on model systems, the application of REM
      in complex systems such as for the simulation of protein and peptide folding in
      explicit solvent has not been objectively tested in detail. Here we present a
      comparison of conventional MD and temperature replica exchange MD (T-REMD)
      simulations of a beta-heptapeptide in explicit solvent. This system has
      previously been shown to undergo reversible folding on the time scales accessible
      to MD simulation and thus allows a direct one-to-one comparison of efficiency.
      The primary properties compared are the free energy of folding and the relative
      populations of different conformers as a function of temperature. It is found
      that to achieve a similar degree of precision T-REMD simulations starting from a
      random set of initial configurations were approximately an order of magnitude
      more computationally efficient than a single 800 ns conventional MD simulation
      for this system at the lowest temperature investigated (275 K). However, whereas
      it was found that T-REMD simulations are more than four times more efficient than
      multiple independent MD simulations at one temperature (300 K) the actual
      increase in conformation sampling was only twofold. The overall gain in
      efficiency using REMD resulted primarily from the ordering of different
      conformational states over temperature, as opposed to a large increase of
      conformational sampling. It is also shown that in this system exchanges are
      accepted primarily based on (random) fluctuations within the solvent and are not
      strongly correlated with the instantaneous peptide conformation raising questions
      in regard to the efficiency of T-REMD in larger systems.

PMID- 17212516
TI  - Theory of relaxation and elasticity in polymer glasses.
AB  - The recently developed activated barrier hopping theory of deeply supercooled
      polymer melts [K. S. Schweizer and E. J. Saltzman, J. Chem. Phys. 121, 1984
      (2004)] is extended to the nonequilibrium glass state. Below the kinetic glass
      temperature T(g), the exact statistical mechanical relation between the
      dimensionless amplitude of long wavelength density fluctuations, S(0), and the
      thermodynamic compressibility breaks down. Proper extension of the theory
      requires knowledge of the nonequilibrium S(0) which x-ray scattering experiments
      find to consist of a material specific and temperature-independent quenched
      disorder contribution plus a vibrational contribution which varies roughly
      linearly with temperature. Motivated by these experiments and general landscape
      concepts, a simple model is proposed for S(0)(T). Deep in the glass state the
      form of the temperature dependence of the segmental relaxation time is found to
      depend sensitively on the magnitude of frozen in density fluctuations. At the
      (modest) sub-T(g) temperatures typically probed in experiment, an effective
      Arrhenius behavior is generically predicted which is of nonequilibrium origin.
      The change in apparent activation energy across the glass transition is
      determined by the amplitude of frozen density fluctuations. For values of the
      latter consistent with experiment, the theory predicts a ratio of effective
      activation energies in the range of 3-6, in agreement with multiple measurements.
      Calculations of the shear modulus for atactic polymethylmethacrylate above and
      below the glass transition temperature have also been performed. The present work
      provides a foundation for the formulation of predictive theories of physical
      aging, the influence of deformation on the alpha relaxation process, and rate
      dependent nonlinear mechanical properties of thermoplastics.

PMID- 17212517
TI  - Aging in a Laponite colloidal suspension: a Brownian dynamics simulation study.
AB  - The authors report Brownian dynamics simulation of the out-of-equilibrium
      dynamics (aging) in a colloidal suspension composed of rigid charged disks, one
      possible model for Laponite, a synthetic clay deeply investigated in the last few
      years by means of various experimental techniques. At variance with previous
      numerical investigations, mainly focusing on static structure and equilibrium
      dynamics, the authors explore the out-of-equilibrium aging dynamics. They analyze
      the wave vector and waiting time dependence of the dynamics, focusing on the
      single-particle and collective density fluctuations (intermediate scattering
      functions), the mean-squared displacement, and the rotational dynamics. Their
      findings confirm the complexity of the out-of-equilibrium dynamical behavior of
      this class of colloidal suspensions and suggest that an arrested disordered state
      driven by a repulsive Yukawa potential, i.e., a Wigner glass, can be observed in
      this model.

PMID- 17212518
TI  - Integral equation theory study on the structure and effective interactions in
      star polymer nanocomposite melts.
AB  - The polymer reference interaction site model theory is used to investigate the
      radial distribution function, potential of mean force, depletion force, and
      second virial coefficient in star polymer nanocomposite melts. The contact
      aggregation of nanoparticles for relatively weak nanoparticle-monomer attraction
      and the bridging aggregation of nanoparticles for very large nanoparticle-monomer
      attraction are observed. The star architecture can well suppress the organization
      states of direct contact and bridging structure for the moderate nanoparticle
      monomer attraction, and promote the bridging-type organization for relatively
      large nanoparticle-monomer attraction. At constant particle volume fraction, the
      arm length quantitatively affects the organization states of star polymer
      nanocomposite melt, and larger repulsive barriers are existent to prevent the
      contact aggregation of larger nanoparticles. These observations provide useful
      information for the development of new nanocomposite materials.

PMID- 17212519
TI  - Improved dissipative particle dynamics simulations of lipid bilayers.
AB  - The authors introduce a new parameterization for the dissipative particle
      dynamics simulations of lipid bilayers. In this parameterization, the
      conservative pairwise forces between beads of the same type in two different
      hydrophobic chains are chosen to be less repulsive than the water-water
      interaction, but the intrachain bead interactions are the same as the water-water
      interaction. For a certain range of parameters, the new bilayer can only be
      stretched up to 30% before it ruptures. Membrane tension, density profiles, and
      the in-plane lipid diffusion coefficient of the new bilayer are discussed in
      detail. They find two kinds of finite size effects that influence the membrane
      tension: lateral finite size effects, for which larger membranes rupture at a
      smaller stretch, and transverse finite size effects, for which tensionless
      bilayers are more compact in larger systems. These finite size effects become
      rather small when the simulation box is sufficiently large.

PMID- 17212520
TI  - Percus-Yevick theory for the structural properties of the seven-dimensional hard
      sphere fluid.
AB  - The direct correlation function and the (static) structure factor for a seven
      dimensional hard-sphere fluid are considered. Analytical results for these
      quantities are derived within the Percus-Yevick [Phys. Rev.110, 1 (1958)] theory.

PMID- 17212521
TI  - Transcutaneous fiber optic Raman spectroscopy of bone using annular illumination
      and a circular array of collection fibers.
AB  - Transcutaneous bone Raman spectroscopy with an exciting annulus of 785-nm laser
      light surrounding the field of view of a circular array of collection fibers is
      demonstrated. The configuration provides distributed laser light. The annulus is
      located 2 to 3 mm beyond the edge of the field of view of the collection fibers
      to reject contributions from skin and other overlying tissues. Data are presented
      for rat and chicken tissue. For rat tibia, the carbonate/phosphate ratio measured
      at a depth of 1 mm below the skin is in error by 2.3% at an integration time of
      120 s and within 10% at a 30-s integration time. For chicken tibia 4 mm below the
      skin surface, the error is less than 8% with a 120-s integration time.

PMID- 17212522
TI  - Visualization of biological texture using correlation coefficient images.
AB  - Subsurface structural features of biological tissue are visualized using
      polarized light images. The technique of Pearson correlation coefficient analysis
      is used to reduce blurring of these features by unpolarized backscattered light
      and to visualize the regions of high statistical similarities within the noisy
      tissue images. It is shown that under certain conditions, such correlation
      coefficient maps are determined by the textural character of tissues and not by
      the chosen region of interest, providing information on tissue structure. As an
      example, the subsurface texture of a demineralized tooth sample is enhanced from
      a noisy polarized light image.

PMID- 17212523
TI  - Methods and application areas of endoscopic optical coherence tomography.
AB  - We review the current state of research in endoscopic optical coherence
      tomography (OCT). We first survey the range of available endoscopic optical
      imaging techniques. We then discuss the various OCT-based endoscopic methods that
      have thus far been developed. We compare the different endoscopic OCT methods in
      terms of their scan performance. Next, we examine the application range of
      endoscopic OCT methods. In particular, we look at the reported utility of the
      methods in digestive, intravascular, respiratory, urinary and reproductive
      systems. We highlight two additional applications--biopsy procedures and
      neurosurgery--where sufficiently compact OCT-based endoscopes can have
      significant clinical impacts.

PMID- 17212524
TI  - Use of polarization-sensitive optical coherence tomography to determine the
      directional polarization sensitivity of articular cartilage and meniscus.
AB  - The directional polarization sensitivity of articular cartilage and meniscus is
      investigated by use of polarization-sensitive optical coherence tomography (PS
      OCT) by varying the angle of incident illumination. Experimental results show
      that when the incident light is perpendicular to the tissue surface, normal
      articular cartilage demonstrates little polarization sensitivity, while meniscus
      demonstrates strong polarization sensitivity. Differences in optical phase
      retardation produced by articular cartilage and meniscus are observed when the
      incident angle of the scanning light beam is adjusted between 0 and 90 deg
      relative to the tissue surface. Directional polarization sensitivity of articular
      cartilage and meniscus as obtained by PS-OCT imaging using variations in the
      angle of incident illumination can be used to assess the orientation and
      organization of the collagen matrix of these tissues. The polarization
      sensitivity as evidenced by the Stokes vector and optical phase retardation
      images can be explained by the orientation of the angle of illumination relative
      to the unique structural organization of the collagen fibrils and fibers of
      articular cartilage and meniscus.

PMID- 17212525
TI  - Noninvasive assessment of cutaneous wound healing using ultrahigh-resolution
      optical coherence tomography.
AB  - Ultrahigh-resolution optical coherence tomography (OCT) was used for noninvasive
      in vivo evaluation of the wound healing process. Cutaneous wounds were induced by
      2.5-mm diameter full-thickness punch biopsies on the dorsal surface of seven
      mice. OCT imaging was performed to assess the structural characteristics
      associated with the healing process. The OCT results were compared to
      corresponding histology. Two automated quantitative analysis routines were
      implemented to identify the dermal-epidermal junction and segment the OCT images.
      Hallmarks of cutaneous wound healing such as wound size, epidermal migration,
      dermal-epidermal junction formation, and differences in wound composition were
      readily identified on the OCT images. Blister formation was also observed.
      Preliminary findings suggest OCT is a viable tool to noninvasively monitor wound
      healing in vivo.

PMID- 17212526
TI  - In vivo ultrahigh-resolution optical coherence tomography of mouse colon with an
      achromatized endoscope.
AB  - Endoscopic ultrahigh-resolution optical coherence tomography (OCT) enables
      collection of minimally invasive cross-sectional images in vivo, which may be
      used to facilitate rapid development of reliable mouse models of colon disease as
      well as assess chemopreventive and therapeutic agents. The small physical scale
      of mouse colon makes light penetration less problematic than in other tissues and
      high resolution acutely necessary. In our 2-mm diameter endoscopic time domain
      OCT system, isotropic ultrahigh-resolution is supported by a center wavelength of
      800 nm and full-width-at-half-maximum bandwidth of 150 nm (mode-locked
      titanium:sapphire laser) combined with 1:1 conjugate imaging of a small core
      fiber. A pair of KZFSN5/SFPL53 doublets provides excellent color correction to
      support wide bandwidth throughout the imaging depth. A slight deviation from
      normal beam exit angle suppresses collection of the strong back reflection at the
      exit window surface. Our system achieves axial resolution of 3.2 microm in air
      and 4.4-microm lateral spot diameter with 101-dB sensitivity. Microscopic
      features too small to see in mouse tissue with conventional resolution systems,
      including colonic crypts, are clearly resolved. Resolution near the cellular
      level is potentially capable of identifying abnormal crypt formation and
      dysplastic cellular organization.

PMID- 17212527
TI  - Volumetric three-dimensional recognition of biological microorganisms using
      multivariate statistical method and digital holography.
AB  - We present a new statistical approach to real-time sensing and recognition of
      microorganisms using digital holographic microscopy. We numerically produce many
      section images at different depths along a longitudinal direction from the single
      digital hologram of three-dimensional (3D) microorganisms in the Fresnel domain.
      For volumetric 3D recognition, the test pixel points are randomly selected from
      the section image; this procedure can be repeated with different specimens of the
      same microorganism. The multivariate joint density functions are calculated from
      the pixel values of each section image at the same random pixel points. The
      parameters of the statistical distributions are compared using maximum likelihood
      estimation and statistical inference algorithms. The performance of the proposed
      system is illustrated with preliminary experimental results.

PMID- 17212528
TI  - Investigation of the homogeneity of the distribution of sunscreen formulations on
      the human skin: characterization and comparison of two different methods.
AB  - The efficacy of sun protection, mostly realized by the application of sunscreen
      formulations, is commonly described by the sun protection factor (SPF). Previous
      investigations have shown that the efficacy of the sun protection inter alia
      depends on the homogeneity of the distribution of the topically applied sunscreen
      formulation on the human skin. Therefore, suitable methods are required to
      determine the homogeneity of topically applied substances on the skin surface.
      This study provides and compares two different methods, which enable this
      determination. Laser scanning microscopy allows the analysis of tape strips
      removed from skin treated with a sunscreen. These reflect the inhomogeneous
      distribution on the skin that can complementary be determined directly, utilizing
      a dermatological laser scanning microscope. For the second method, a chromatic
      confocal setup was utilized, which enables the study of the microtopography of
      skin replicas before and after the application of a sunscreen product. The two
      methods were applied for the evaluation of three different sunscreen formulations
      for each method. A correlation of the homogeneity of distribution with the in
      vivo SPF could be confirmed. Both methods are suitable to investigate the
      homogeneity of the tested sunscreen formulations, although they provide different
      advantages and disadvantages.

PMID- 17212529
TI  - Evaluation of dermal thermal damage by multiphoton autofluorescence and second
      harmonic-generation microscopy.
AB  - We attempt to characterize the degree of skin thermal damage by using multiphoton
      microscopy to characterize dermal thermal damage. Our results show that dermal
      collagen and elastic fibers display different susceptibility to thermal injury.
      Morphologically, dermal collagen starts to denature at 60 degrees C while
      fracture and aggregation of elastic fibers do not occur until 65 degrees C. With
      increasing temperatures, the structures of both elastic and collagen fibers
      deteriorate. While second-harmonic-generation (SHG) imaging is helpful in
      identifying the denaturation temperature of collagen, autofluorescence (AF)
      imaging can help to identify the structural alternations of tissue at higher
      temperatures when SHG signals have decayed. We also employ a ratiometric approach
      based on the AF-to-SHG index of dermis (ASID) to characterize the degree of
      dermal thermal damage. Use of the ASID index can bypass the difficulty in
      analyzing inhomogeneous dermal fibers and show that dermal collagen starts to
      denature at 60 degrees C. Our results suggest that with additional developments,
      multiphoton microscopy has potential to be developed into an effective in vivo
      imaging technique to monitor and characterize dermal thermal damage.

PMID- 17212530
TI  - Estimation of subcellular particle size histograms with electron microscopy for
      prediction of optical scattering in breast tissue.
AB  - Diffuse near-infrared tomography of tissue reveals scattering changes that
      originate from the submicroscopic features of the tissue; yet the existing tools
      to use this information to predict which features contribute to the scattering
      spectrum are limited by the lack of direct data quantifying the particle sizes.
      Breast tissue was examined with electron microscopy, and analysis showed that the
      distributions of particle sizes appear in double exponential functions for most
      cellular tissues. The average particle size histograms of high-grade cancer, low
      grade cancer, fibroglandular tissue, and adipose tissue were examined. The
      particle histograms were progressively decreasing in magnitude for these tissue
      types, and the average size of the particles increased, for these four tissues,
      respectively. Typical particle sizes in the range of 10 to 500 nm for these
      tissue types, with biexponential fitting, gave two particle distributions: one
      near 20 to 25 nm for the smaller size and one at 110 to 230 nm for the larger
      distributions. Mie scatter theory was used to take these particle distributions
      and calculate scattering spectra. The ability to image reduced scattering
      coefficient spectra of bulk breast tissues exists, and so this data provides
      insight into how bulk imaging may be mapped over to predict factors related to
      the tissue ultrastructure.

PMID- 17212531
TI  - Rapid and conservative ablation and modification of enamel, dentin, and alveolar
      bone using a high repetition rate transverse excited atmospheric pressure CO2
      laser operating at lambda=9.3 micro.
AB  - Transverse excited atmospheric pressure (TEA) CO(2) lasers tuned to the strong
      mineral absorption of hydroxyapatite near lambda=9 microm are well suited for the
      efficient ablation of dental hard tissues if the laser pulse is stretched to
      greater than 5 to 10 micros to avoid plasma shielding phenomena. Such CO(2)
      lasers are capable of operating at high repetition rates for the rapid removal of
      dental hard tissues. The purpose of this study was to test the hypothesis that
      stretched lambda=9.3-microA CO(2) laser pulses can produce lateral incisions in
      enamel, dentin, and alveolar bone for dental restorations and implants at
      repetition rates as high as 400 Hz without peripheral thermal damage. The single
      pulse ablation rates through enamel, dentin, and bone were determined for
      incident fluence ranging from (1 to 160 J/m(2)) for laser pulses from 5 to 18 mus
      in duration. Lateral incisions were produced in hard tissue samples using a
      computer-controlled scanning stage and water spray, and the crater morphology and
      chemical composition were measured using optical microscopy and high-resolution
      synchrotron radiation infrared spectromicroscopy. The residual energy remaining
      in tooth samples was measured to be 30 to 40% for enamel and 20 to 30% for dentin
      without water cooling, under optimum irradiation intensities, significantly lower
      than for longer CO(2) laser pulses. The transmission through 2-m length 300-, 500
      , 750-, and 1000-microm silica hollow waveguides was measured and 80%
      transmission was achieved with 40 mJ per pulse. These results suggest that high
      repetition rate TEA CO(2) laser systems operating at lambda=9.3 microm with pulse
      durations of 10 to 20 micros are well suited for dental applications.

PMID- 17212532
TI  - Use of Fourier transform infrared microscopy for the evaluation of drug
      efficiency.
AB  - Fourier transform infrared (FTIR) spectroscopy has been used by chemists as a
      powerful tool to characterize inorganic and organic compounds. In this study, we
      examine the potential of FTIR microspectroscopy for early evaluation of therapy
      efficiency. For this purpose, we examine the effect of acyclovir (a known
      antiherpetic drug) on the development of herpes simplex virus type 1 (HSV-1)
      infection in cell culture. Also, we examine spectral changes in lymphocytes
      obtained from leukemia patients after appropriate chemotherapy treatment. Our
      results show early and significant spectral indicators for successful infection
      of Vero cells with HSV-1. Treatment of these infected cells with increasing doses
      of acyclovir reduces clearly the spectral changes caused by the infection in a
      correlation with inhibiting the development of the cytopathic effect (CPE)
      induced by this virus. Also significant and consistent spectral differences
      between lymphocytes from human leukemia patients compared to that from healthy
      persons are obtained. Treatment of these leukemia patients with appropriate drugs
      reduces significantly these spectral differences in a correlation with the
      improvement of the patient's clinical situation. It seems that FTIR spectroscopy
      can be used as an effective tool for early evaluation of the efficiency of drugs.

PMID- 17212533
TI  - Endoscopic cellular microscopy for in vivo biomechanical assessment of tendon
      function.
AB  - This study explores a novel method to quantify in vivo soft tissue biomechanics
      from endoscopic confocal fluorescence microscope images of externally loaded
      biological tissues. A custom algorithm based on normalized cross-correlation is
      used to track fluorescently labeled cells within soft tissue structures as they
      deform. Cellular displacements are subsequently reduced to tissue strains by
      deriving the spatial gradient of the spline smoothed cellular displacement field.
      The relative performance of the tracking method is verified using a synthetic
      dataset with known underlying deformation. In biological application of the
      method, tissue strains are measured in the Achilles tendon of an anesthetized
      mouse. Over repeated trials, structural strain in the tendon (i.e., the relative
      change in distance between cells located at view field extremes) is 20.3+/-3.1%,
      thus establishing the reproducibility of the loading protocol. Analysis of local
      tendon tissue strains reveal primary engineering strains in the tissue to range
      from 5 to 55%, signifying a highly inhomogeneous strain state, with complex
      relative motions of neighboring tendon substructures. In summary, the current
      work establishes a baseline for a promising experimental method, and demonstrates
      its technical feasibility.

PMID- 17212534
TI  - High-speed confocal fluorescence imaging with a novel line scanning microscope.
AB  - Research in the life sciences increasingly involves the investigation of fast
      dynamic processes at the cellular and subcellular level. It requires tools to
      image complex systems with high temporal resolution in three-dimensional space.
      For this task, we introduce the concept of a fast fluorescence line scanner
      providing image acquisition speeds in excess of 100 frames per second at 512 x
      512 pixels. Because the system preserves the capability for optical sectioning of
      confocal systems, it allows us to observe processes with three-dimensional
      resolution. We describe the principle of operation, the optical characteristics
      of the microscope, and cover several applications in particular from the field of
      cell and developmental biology. A commercial system based on the line scanning
      concept has been realized by Carl Zeiss (LSM 5 LIVE).

PMID- 17212535
TI  - Intrinsic fluorescence and redox changes associated with apoptosis of primary
      human epithelial cells.
AB  - Apoptosis plays a key role in the development and maintenance of human tissues.
      This process has been studied traditionally in cells that are stained with
      exogenous fluorophores. These approaches affect cell viability, and thus are ill
      suited for in vivo applications. We present an imaging approach that can identify
      apoptotic cells in living cell populations based on detection and quantification
      of distinct changes in the intensity and localization of cellular
      autofluorescence. Specifically, we acquire NAD(P)H, FAD, and redox ratio
      autofluorescence images of primary keratinocytes following 1, 9, 14, and 18 h of
      treatment with cisplatin, a known apoptosis-inducing chemotherapy agent. We find
      that intense autofluorescence combined with a low redox fluorescence ratio is
      progressively confined to a gradually smaller perinuclear cytoplasmic region with
      cisplatin treatment. Studies with exogenous nuclear fluorophores demonstrate that
      these autofluorescence changes occur at early stages of apoptosis. Additional
      costaining experiments suggest that this strongly autofluorescent, highly
      metabolically active perinuclear ring represents a subpopulation of mitochondria
      that are mobilized in response to the apoptotic stimulus and may provide the
      energy required to execute the final apoptotic steps. Thus, autofluorescence
      localization changes could serve as a sensitive, noninvasive indicator of early
      apoptosis in vivo.

PMID- 17212536
TI  - Standing wave total internal reflection fluorescence microscopy to measure the
      size of nanostructures in living cells.
AB  - We present the first application of standing wave fluorescence microscopy (SWFM)
      to determine the size of biological nanostructures in living cells. The improved
      lateral resolution of less than 100 nm enables superior quantification of the
      size of subcellular structures. We demonstrate the ability of SWFM by measuring
      the diameter of biological nanotubes (membrane tethers formed between cells). The
      combination of SWFM with total internal reflection (TIR), referred to as SW
      TIRFM, allows additional improvement of axial resolution by selective excitation
      of fluorescence in a layer of about 100 nm.

PMID- 17212537
TI  - Diagnosis of peritonitis using near-infrared optical imaging of in vivo labeled
      monocytes-macrophages.
AB  - Peritonitis is an inflammatory process characterized by massive monocytes
      macrophages infiltration. Since early diagnosis is important for a successful
      therapeutic outcome, the feasibility for a selective labeling and imaging of
      macrophages for highly sensitive optical imaging was assessed. After in vitro
      incubation of mouse macrophages J774A.1 with the far-red/near-infrared
      fluorochrome DY-676, distinct fluorescence intensities (1026+/-142 a.u.) were
      detected as compared to controls (552+/-54 a.u.) using a whole-body small animal
      near-infrared fluorescence (NIRF) imaging system. Macrophage labeling was
      confirmed by confocal laser scanning microscopy (CLSM) and fluorescence-activated
      cell sorting, (FACS). The fluorochrome was also found to be predominantly
      distributed within compartments in the cytoplasm. Additionally, peritonitis was
      induced in mice by intraperitoneal injection of zymosanA. After intravenous
      injection of fluorochrome (55 nmol/kg) and using whole-body fluorescence imaging,
      higher fluorescence intensities (869+/-151 a.u.) were detected in the peritoneal
      area of diseased mice as compared to controls (188+/-41 a.u.). Furthermore, cells
      isolated from peritoneal lavage revealed the presence of labeled monocytes
      macrophages. The results indicate that in vivo diagnosis of peritonitis by near
      infrared optical imaging of labeled monocytes-macrophages is feasible. Possibly,
      early stages of other inflammatory diseases could also be detected by the
      proposed diagnostic method in the long term.

PMID- 17212538
TI  - Comparison between a time-domain and a frequency-domain system for optical
      tomography.
AB  - The quality of phase and amplitude data from two medical optical tomography
      systems were compared. The two systems are a 32-channel time-domain system
      developed at University College London (UCL) and a 16-channel frequency-domain
      system developed at Helsinki University of Technology (HUT). Difference data
      measured from an inhomogeneous and a homogeneous phantom were compared with a
      finite-element method (diffusion equation) and images of scattering and
      absorption were reconstructed based on it. The measurements were performed at
      measurement times between 1 and 30 s per source. The mean rms errors in the data
      measured by the HUT system were 3.4% for amplitude and 0.51 deg for phase, while
      the corresponding values for the UCL data were 6.0% and 0.46 deg, respectively.
      The reproducibility of the data measured with the two systems was tested with a
      measurement time of 5 s per source. It was 0.4% in amplitude for the HUT system
      and 4% for the UCL system, and 0.08 deg in phase for both systems. The image
      quality of the reconstructions from the data measured with the two systems were
      compared with several quantitative criteria. In general a higher contrast was
      observed in the images calculated from the HUT data.

PMID- 17212539
TI  - Compression-induced changes in the physiological state of the breast as observed
      through frequency domain photon migration measurements.
AB  - We use optical spectroscopy to characterize the influence of mammographic-like
      compression on the physiology of the breast. We note a reduction in total
      hemoglobin content, tissue oxygen saturation, and optical scattering under
      compression. We also note a hyperemic effect during repeated compression cycles.
      By modeling the time course of the tissue oxygen saturation, we are able to
      obtain estimates for the volumetric blood flow (1.64+/-0.6 mL/100 mL/min) and the
      oxygen consumption (1.97+/-0.6 micromol/100 mL/min) of compressed breast tissue.
      These values are comparable to estimates obtained from previously published
      positron emission tomography (PET) measurements. We conclude that compression
      induced changes in breast physiological properties are significant and should be
      accounted for when performing optical breast imaging. Additionally, the dynamic
      characteristics of the changes in breast physiological parameters, together with
      the ability to probe the tissue metabolic state, may prove useful for breast
      cancer detection.

PMID- 17212540
TI  - Time-resolved imaging of optical coefficients through murine chest cavities.
AB  - As small animal optical imaging and tomography are gaining popularity for
      interrogating functional and molecular events in vivo, it becomes increasingly
      necessary to gain knowledge of the optical properties of the species investigated
      to better understand and describe photon propagation through their tissues. To
      achieve characterization of the spatial variation of average optical properties
      through murine chest cavities, time- and spatially resolved measurements of femto
      second laser pulse transmission are performed through mice using a high-speed
      gated image intensifier. Application of time-resolved diffusion theory for finite
      slab geometry is first confirmed on phantoms and then applied to in vivo
      measurements for spatially resolving and quantifying mouse optical properties.
      Photon transmission images through mouse chest cavities are further obtained at
      different time gates to visualize the spatial variation observed and confirm the
      optical coefficient patterns calculated.

PMID- 17212542
TI  - Improving performance of reflectance diffuse optical imaging using a
      multicentered mode.
AB  - We propose a novel multicentered mode for arrangement of optical fibers to
      improve the imaging performance of reflectance diffuse optical imaging (rDOI).
      Simulations performed using a semi-infinite model show that the proposed
      multicentered geometries can achieve a maximum of 42 overlapping measurements.
      The contrast-to-noise ratio (CNR) analysis indicates that the best spatial
      resolution is 1 mm in radius and the contrast resolution is less than 1.05 for
      the multicentered geometries. The results from simulations indicate significant
      improvement in image quality compared to the single-centered mode and previous
      geometries. Additional experimental results on a single human subject lead to the
      conclusion that the proposed multicentered geometries are appropriate for
      exploring activations in the human brain. From the results of this research, we
      conclude that the proposed multicentered mode could advance the performance of
      rDOI both in image quality and practical convenience.

PMID- 17212541
TI  - Quantitative spatial comparison of diffuse optical imaging with blood oxygen
      level-dependent and arterial spin labeling-based functional magnetic resonance
      imaging.
AB  - Akin to functional magnetic resonance imaging (fMRI), diffuse optical imaging
      (DOI) is a noninvasive method for measuring localized changes in hemoglobin
      levels within the brain. When combined with fMRI methods, multimodality
      approaches could offer an integrated perspective on the biophysics, anatomy, and
      physiology underlying each of the imaging modalities. Vital to the correct
      interpretation of such studies, control experiments to test the consistency of
      both modalities must be performed. Here, we compare DOI with blood oxygen level
      dependent (BOLD) and arterial spin labeling fMRI-based methods in order to
      explore the spatial agreement of the response amplitudes recorded by these two
      methods. Rather than creating optical images by regularized, tomographic
      reconstructions, we project the fMRI image into optical measurement space using
      the optical forward problem. We report statistically better spatial correlation
      between the fMRI-BOLD response and the optically measured deoxyhemoglobin
      (R=0.71, p=1x10(-7)) than between the BOLD and oxyhemoglobin or total hemoglobin
      measures (R=0.38, p=0.04|0.37, p=0.05, respectively). Similarly, we find that the
      correlation between the ASL measured blood flow and optically measured total and
      oxyhemoglobin is stronger (R=0.73, p=5x10(-6) and R=0.71, p=9x10(-6),
      respectively) than the flow to deoxyhemoglobin spatial correlation (R=0.26,
      p=0.10).

PMID- 17212543
TI  - Effects of vasodilation on intrinsic optical signals in the mammalian brain: a
      phantom study.
AB  - Using a broadband spectral technique, we recently showed [J. Biomed. Opt. 10,
      064009 (2005)] that during visual stimulation of the cat brain there were not
      only changes in oxy- and deoxyhemoglobin levels, reminiscent of the optical blood
      oxygenation level dependence (BOLD) effect reported in humans, but also the
      apparent water content of the tissue and the optical scattering contribution
      decreased during stimulation. These relatively fast changes (in seconds) in water
      tissue content are difficult to explain in physiological terms. We developed a
      simple model to explain how local vasodilation, which occurs as a result of the
      stimulation, could cause this apparent change in water content. We show that in a
      phantom model we can obtain spectral effects similar to those observed in the cat
      brain such as the apparent decrease of the water spectral component without
      changing the water content of the bath in which the phantom measurements were
      performed. Furthermore, using the phantom model, we show that the relative
      apparent changes in the spectral components due to vasodilation during
      stimulation are roughly comparable in magnitude to the changes in tissue
      chromophores due to the optical equivalent of the BOLD effect reported in the
      literature.

PMID- 17212544
TI  - Noninvasive diffuse optical measurement of blood flow and blood oxygenation for
      monitoring radiation therapy in patients with head and neck tumors: a pilot
      study.
AB  - This pilot study explores the potential of noninvasive diffuse correlation
      spectroscopy (DCS) and diffuse reflectance spectroscopy (DRS) for monitoring
      early relative blood flow (rBF), tissue oxygen saturation (StO(2)), and total
      hemoglobin concentration (THC) responses to chemo-radiation therapy in patients
      with head and neck tumors. rBF, StO(2), and THC in superficial neck tumor nodes
      of eight patients are measured before and during the chemo-radiation therapy
      period. The weekly rBF, StO(2), and THC kinetics exhibit different patterns for
      different individuals, including significant early blood flow changes during the
      first two weeks. Averaged blood flow increases (52.7+/-9.7)% in the first week
      and decreases (42.4+/-7.0)% in the second week. Averaged StO(2) increases from
      (62.9+/-3.4)% baseline value to (70.4+/-3.2)% at the end of the second week, and
      averaged THC exhibits a continuous decrease from pretreatment value of (80.7+/
      7.0) [microM] to (73.3+/-8.3) [microM] at the end of the second week and to
      (63.0+/-8.1) [microM] at the end of the fourth week of therapy. These preliminary
      results suggest daily diffuse-optics-based therapy monitoring is feasible during
      the first two weeks and may have clinical promise.

PMID- 17212545
TI  - Development and validation of a multiwavelength spatial domain near-infrared
      oximeter to detect cerebral hypoxia-ischemia.
AB  - Detection of cerebral hypoxia-ischemia in infants remains problematic, as current
      monitors in clinical practice are impractical, insensitive, or nonspecific. Our
      study develops a multiwavelength spatial domain construct for near-infrared
      spectroscopy (NIRS) to detect cerebral hypoxia-ischemia and evaluates the
      construct in several models. The NIRS probe contains photodiode detectors 2, 3,
      and 4 cm from a three-wavelength, light-emitting diode. A construct determines
      cerebral O(2) saturation based on spatial domain principles. Device performance
      and construct validity are examined in in-vitro models simulating the brain, and
      in piglets subjected to hypoxia, hypoxia-ischemia, and hyperoxic conditions using
      a weighted average of arterial and cerebral venous O(2) saturation measured by CO
      oximetry. The results in the brain models verify key equations in the construct
      and demonstrate reliable performance of the device. In piglets, the device
      measures cerebral O(2) saturation with bias +/-4% and precision +/-8%. In
      conclusion, this NIRS device accurately detects cerebral hypoxia-ischemia and is
      of a design that is practical for clinical application.

PMID- 17212546
TI  - Statistical comparison of Fourier transform infrared spectra.
AB  - Spectroscopic assessment of whether a biological sample has changed as a result
      of processing or degradation is generally carried out by qualitative comparison
      of spectra, without statistical analysis, resulting in a subjective evaluation of
      sample stability. Here, we present a formalism for quantitative statistical
      comparison of signal-averaged Fourier transform infrared spectra, commonly used
      to assess molecular properties of biological samples. Expressions are derived
      permitting the comparison of 1. single beam spectra; 2. transmittance spectra
      obtained by calculating the ratio of single beam spectra of a sample and
      background; and 3. absorbance spectra derived from transmittance spectra. An
      application of these results to the degradation of cartilage is presented. Two
      absorbance spectra of a cartilage sample taken in succession are found to be
      statistically identical with respect to the ratio of the amplitude of the amide I
      band to the amplitude of the amide II band. However, a spectrum of the same
      sample acquired after a 24-h degradation period, while similar to the spectrum of
      the fresh sample, is found to have an altered ratio of these spectral band
      amplitudes, consistent with degradation of the cartilage matrix.

PMID- 17212547
TI  - Comparison of vibrational spectroscopy to biochemical and flow cytometry methods
      for analysis of the basic biochemical composition of mammalian cells.
AB  - We have conducted an extensive comparison of cellular biochemical composition
      obtained from infrared and Raman spectra of intact cells with measurements using
      standard extraction and chemical analysis (including NMR), and flow cytometric
      assay on fixed cells. Measurements were conducted on a rat fibroblast
      carcinogenesis model consisting of normal and tumorigenic cells assayed as
      exponentially growing and plateau-phase cultures. Estimates of protein, DNA, RNA,
      lipids, and glycogen amounts were obtained from a previous publication in which
      vibrational spectra were fit to a set of basis spectra representing protein, DNA,
      RNA, lipids, and glycogen. The Raman spectral estimates of absolute cellular
      composition were quite similar to the independent biochemical and flow cytometric
      assays. The infrared spectra gave similar results for protein, lipid, and
      glycogen but underestimated the DNA content while overestimating the RNA level.
      When ratios of biochemical concentrations in exponential and plateau-phase
      cultures were examined, the Raman spectroscopic results were the same, within
      errors, as the independent methods, in all cases. Several changes in relative
      biochemical composition due to tumorigenic and proliferative status previously
      reported using vibrational spectroscopy were confirmed by the independent
      methods. These results demonstrate that vibrational spectroscopy can provide
      reliable estimates of the biochemical composition of mammalian cells.

PMID- 17212548
TI  - Lycopene is more potent than beta carotene in the neutralization of singlet
      oxygen: role of energy transfer probed by ultrafast Raman spectroscopy.
AB  - Energy transfer processes between beta carotene, lycopene, and singlet oxygen
      ((1)O(2)) have been studied by ultrafast Raman spectroscopy. Our experimental
      results demonstrate that during the neutralization of singlet oxygen by beta
      carotene the excitation energy of singlet oxygen is transferred directly to the
      first excited electronic state S(1) of beta carotene. In contrast, the excitation
      energy of singlet oxygen is transferred directly to the ground excited vibronic
      state S(0) of lycopene. Our data not only provide the first direct experimental
      elucidation of energy transfer processes in such important biological systems but
      also help explain why lycopene is a more potent antioxidant than beta carotene in
      the neutralization of singlet oxygen.

PMID- 17212549
TI  - Optical properties of normal and cancerous human skin in the visible and near
      infrared spectral range.
AB  - Differences in absorption and/or scattering of cancerous and normal skin have the
      potential to provide a basis for noninvasive cancer detection. In this study, we
      have determined and compared the in vitro optical properties of human epidermis,
      dermis, and subcutaneous fat with those of nonmelanoma skin cancers in the
      spectral range from 370 to 1600 nm. Fresh specimens of normal and cancerous human
      skin were obtained from surgeries. The samples were rinsed in saline solution and
      sectioned. Diffuse reflectance and total transmittance were measured using an
      integrating sphere spectrophotometer. Absorption and reduced scattering
      coefficients were calculated from the measured quantities using an inverse Monte
      Carlo technique. The differences between optical properties of each normal tissue
      cancer pair were statistically analyzed. The results indicate that there are
      significant differences in the scattering of cancerous and healthy tissues in the
      spectral range from 1050 to 1400 nm. In this spectral region, the scattering of
      cancerous lesions is consistently lower than that of normal tissues, whereas
      absorption does not differ significantly, with the exception of nodular basal
      cell carcinomas (BCC). Nodular BCCs exhibit significantly lower absorption as
      compared to normal skin. Therefore, the spectral range between 1050 and 1400 nm
      appears to be optimal for nonmelanoma skin cancer detection.

PMID- 17212550
TI  - Spatially resolved reflectance spectroscopy for diagnosis of cervical precancer:
      Monte Carlo modeling and comparison to clinical measurements.
AB  - We present Monte Carlo modeling studies to provide a quantitative understanding
      of contrast observed in spatially resolved reflectance spectra of normal and
      highly dysplastic cervical tissue. Simulations have been carried out to analyze
      the sensitivity of spectral measurements to a range of changes in epithelial and
      stromal optical properties that are reported to occur as dysplasia develops and
      to predict reflectance spectra of normal and highly dysplastic tissue at six
      different source-detector separations. Simulation results provide important
      insights into specific contributions of different optical parameters to the
      overall spectral response. Predictions from simulations agree well with in vivo
      measurements from cervical tissue and successfully describe spectral differences
      observed in reflectance measurements from normal and precancerous tissue sites.
      Penetration depth statistics of photons detected at the six source-detector
      separations are also presented to reveal the sampling depth profile of the fiber
      optic probe geometry simulated. The modeling studies presented provide a
      framework to meaningfully interpret optical signals obtained from epithelial
      tissues and to optimize design of optical sensors for in vivo reflectance
      measurements for precancer detection. Results from this study can facilitate
      development of analytical photon propagation models that enable inverse
      estimation of diagnostically relevant optical parameters from in vivo reflectance
      measurements.

PMID- 17212551
TI  - Modeling thermal damage in skin from 2000-nm laser irradiation.
AB  - An optical-thermal-damage model of the skin under laser irradiation is developed
      by using finite-element modeling software (FEMLAB 3.1, Comsol, Incorporated,
      Burlington, Massachusetts). The general model simulates light propagation, heat
      generation, transient temperature response, and thermal damage produced by a
      radically symmetric laser beam of normal incidence. Predictions from the model
      are made of transient surface temperatures and the thermal damage on a pigskin
      surface generated by 2000-nm laser irradiation, and these predictions are
      compared to experimental measurements. The comparisons validate the model
      predictions, boundary conditions, and optical, thermal, and rate process
      parameters. The model enables the authors to verify the suitability of the
      American National Standards Institute (ANSI) maximum permissible exposure (MPE)
      standard for a wavelength of 2000 nm with exposure duration from 0.1 to 1 s and
      3.5-mm beam diameter. Compared with the ANSI MPE standard, however, the MPE
      values predicted by the model are higher for exposure durations less than 0.1 s.
      The model indicates that it may be necessary to modify the ANSI MPE standard for
      cases in which the laser-beam diameter is larger than 3.5 mm when a "safety
      factor" of ten is used. A histopathological analysis of the skin damage is
      performed to determine the mechanisms of laser-induced damage in the skin.

PMID- 17212553
TI  - Near-infrared imaging of fast intrinsic optical responses in visible light
      activated amphibian retina.
AB  - High performance functional imaging is needed for dynamic measurements of neural
      processing in retina. Emerging techniques for visual prosthesis also require
      advanced methodology for reliable validation of electromagnetic stimulation of
      the retina. Imaging of fast intrinsic optical responses associated with neural
      activation promises a variety of technical advantages over traditional single and
      multichannel electrophysiological techniques for these purposes, but the
      application of fast optical signals for neural imaging has been limited by low
      signal-to-noise ratio and high background light intensity. However, by using an
      optimized near-infrared probe light and improved optical system, we improve the
      optical signals substantially, allowing single pass measurements with
      approximately micron resolution. We image fast intrinsic optical responses with
      different optical modalities, i.e., bright field, dark field, and cross
      polarization, from isolated retina activated by visible light stimulation. At
      single cell resolution, bright-field imaging discloses the maxima of optical
      responses approximately 5% dI/I, where dI is the dynamic optical change and I is
      the baseline light intensity. Dark-field imaging techniques further enhance the
      sensitivity of optical measurements, and show the maxima of optical responses
      exceeding 10% dI/I. Cross-polarized imaging provides optical sensitivity similar
      to dark-field imaging, but different patterns of neural activation are observed.

PMID- 17212552
TI  - Level-set algorithm for the reconstruction of functional activation in near
      infrared spectroscopic imaging.
AB  - We introduce a new algorithm for the reconstruction of functional brain
      activations from near-infrared spectroscopic imaging (NIRSI) data. While NIRSI
      offers remarkable biochemical specificity, the attainable spatial resolution with
      this technique is rather limited, mainly due to the highly scattering nature of
      brain tissue and the low number of measurement channels. Our approach exploits
      the support-limited (spatially concentrated) nature of the activations to make
      the reconstruction problem well-posed. The new algorithm considers both the
      support and the function values of the activations as unknowns and estimates them
      from the data. The support of the activations is represented using a level-set
      scheme. We use a two-step alternating iterative scheme to solve for the
      activations. Since our approach uses the inherent nature of functional
      activations to make the problem well-posed, it provides reconstructions with
      better spatial resolution, fewer artifacts, and is more robust to noise than
      existing techniques. Numerical simulations and experimental data indicate a
      significant improvement in the quality (resolution and robustness to noise) over
      standard techniques such as truncated conjugate gradients (TCG) and simultaneous
      iterative reconstruction technique (SIRT) algorithms. Furthermore, results on
      experimental data obtained from simultaneous functional magnetic resonance
      imaging (fMRI) and optical measurements show much closer agreement of the optical
      reconstruction using the new approach with fMRI images than TCG and SIRT.

PMID- 17212554
TI  - Fast assessment of the central macular pigment density with natural pupil using
      the macular pigment reflectometer.
AB  - We built a new macular pigment reflectometer (MPR) for fast and objective
      measuring of the optical density of macular pigment in the human eye, using the
      undilated eye. The design is based on the spectral reflectance from a spot of
      white light at the fovea. To evaluate its performance, we measured the macular
      pigment of 20 healthy subjects, ages 18 to 79 years, under four conditions: (1)
      natural pupil in the dark, (2) natural pupil with dim room light, (3) dilated
      pupil in the dark, and for comparison with a different technique, (4)
      heterochromatic flicker photometry (HFP) in dim room light with natural pupil.
      Condition 1 was repeated in a subset of 10 subjects after an interval of at least
      3 days. Data analysis with a model of reflectors and absorbers in the eye
      provided the density of the macular pigment in conditions 1 to 3. Dim room light
      and pupil dilatation had no influence on measured density. Mean within subjects
      variation was typically 7%. Mean difference between test and retest after at
      least 3 days was 1%. Correlation between MPR and HFP was r=0.56 (p=0.012). Mean
      within subjects variation with HFP was 19%. The new instrument holds promise for
      specific applications such as epidemiological research.

PMID- 17212555
TI  - Theory concerning the ablation of corneal tissue with large-area, 193-nm excimer
      laser beams.
AB  - Excimer laser beams (193 nm) of uniform fluence were studied to find out why they
      produce corneal ablations deeper at the edge than the center. Ablation depth
      profiles were taken of porcine corneas, including five dehydrated samples.
      Hydrated corneas and polymethyl methacrylate were ablated with and without
      central masks. Ablation plumes were photographed. Hydrated porcine corneas showed
      patterns of central underablation. As the incident beam increased, the crater
      exhibited increasingly shallower central ablation while maintaining nearly
      constant depth at the edges. Dehydrated corneas did not vary significantly. Masks
      did not alter the depth or shape of craters near ablation edges, but depth
      adjacent to the images of the masks was more than twice that with no mask. Depth
      adjacent to the mask image was nearly the same as at the edge of the zone. The
      rate of change in depth with position was nearly equal in both areas. Maximum
      plume density was centered over the entire ablation with and without the mask.
      Redeposition of plume particles is not the major cause of central underablation.
      Propagating transverse energy from the absorption of photons by peptide bonds
      increases pressure on excited components within the irradiated area, increasing
      recombination, which raises the ablation threshold.

PMID- 17212556
TI  - Laser retinal thermal damage threshold: impact of small-scale ocular motion.
AB  - The impact of the small-scale ocular motion that occurs during steady gaze on the
      retinal thermal damage threshold for long-duration laser exposures is
      investigated. Exposure durations from 100 msec to 50 sec are considered.
      Experimentally recorded eye movement data are input into a numerical simulation
      to calculate the increase in temperature experienced by the retina during an
      exposure to a continuous wave laser. Calculations are for a small retinal beam
      spot. An Arrhenius damage integral is used to estimate the thermal damage
      threshold. The impact of the ocular movements is expressed as a relief factor
      chi, defined as the ratio of the theoretical damage threshold in the presence of
      ocular motion to the threshold calculated assuming no eye motion. The relief
      factor is found to be 1.05 for a 100-msec exposure, increasing to 1.3 for a 50
      sec exposure. The relief factor is described well by the equation
      chi=1.12tau(0.037) for exposure durations tau in the range 100 msec to 50 sec.

PMID- 17212557
TI  - Superhigh-sensitivity photothermal monitoring of individual cell response to
      antitumor drug.
AB  - We describe and explore the capability of a photothermal (PT) assay with modified
      schematics for highly sensitive detection of individual cell response to
      antitumor drug impact in vitro. Specifically, we used the nonlinear differential
      PT test to measure distinctive changes of specific PT parameters after exposure
      of KB3 carcinoma cells to the antitumor drug vinblastine in the broad
      concentration range of 10(-10) to 300 nM. Verification of the PT assay was
      performed by comparison with multidrug-resistant cells and comparison with
      conventional assays evaluating cell viability, cytochrome c release, apoptosis
      induction, and cell size. We demonstrate that this system is capable of detecting
      drug-induced signals at a concentration threshold sensitivity at least seven
      orders of magnitude better than existing assays. We anticipate that this
      technique may serve as a convenient and rapid analytical tool to evaluate the
      presence of intracellular drug, with applications in high throughput screening
      assays and for studying drug uptake and distribution in more complex biological
      or clinical samples.

PMID- 17212558
TI  - Method used to measure interaction of proteins with dual-beam optical tweezers.
AB  - In the force measurement of protein-protein interaction, proteins are usually
      attached to microbeads, so the coated beads serve as both handles and force
      transducers. Due to the short interaction distance between proteins, the beads
      are usually close enough to each other. When dual-beam optical tweezers and
      quadrant photodiode detector are used to investigate the interaction of proteins,
      it is found that the signal of detected beads is greatly affected by adjacent
      beads. Analysis reveals that the contribution of two beads to the quadrant
      detector signal is independent. A method for extracting the real interaction
      signal from a disturbed one is presented. Based on this method, interaction
      between microtubules and AtMAP65-1 is measured. The results show that this method
      is useful for measuring short-distance interaction with the precision of
      piconewton and nanometer scales.

PMID- 17212560
TI  - Cell membrane and gold nanoparticles effects on optical immersion experiments
      with noncancerous and cancerous cells: finite-difference time-domain modeling.
AB  - Pilot results on the application of the finite-difference time-domain (FDTD)
      approach for studying the implementation of the optical immersion technique for
      the visualization of single and multiple gold nanoparticles in biological cells
      are presented. We focus on two different scenarios considering single biological
      cells containing (1) cytoplasm, nucleus, and membrane and (2) cytoplasm, nucleus,
      gold nanoparticles, and membrane. To the best of our knowledge, this is the first
      time the cell membrane thickness and gold nanoparticle effects on the forward
      scattered light from biological cells are discussed. The applicability and the
      potential of the FDTD approach for studying optical immersion technique enhanced
      bioimaging is demonstrated.

PMID- 17212559
TI  - Fluorescence spectroscopy and imaging of myocardial apoptosis.
AB  - Fluorometry is used to detect intrinsic flavoprotein (FP) and nicotinamide
      adenine dinucleotide (NADH) signals in an open-chest rabbit model of myocardial
      ischemia-reperfusion injury. Myocyte apoptosis has been shown clinically to
      contribute to infarct size following reperfusion of ischemic myocardium. A
      noninvasive means of assessing apoptosis in this setting would aid in the
      treatment of subsequent ventricular remodeling. We show that in vivo fluorometry
      can be useful in apoptosis detection in open-chest surgeries. Specific changes in
      myocardial redox states have been shown to indicate the presence of apoptosis.
      Two main mitochondrial intrinsic fluorophores, NADH and FP signals, were measured
      during normoxia, ischemia, and reperfusion experimental protocol. Ischemia was
      induced by occlusion of the largest branch of the circumflex coronary artery and
      fluorescence signals are collected by applying two different fluorescence
      techniques: in vivo fluorometry and postmortem cryoimaging. The first technique
      was employed to detect FP and NADH signals in vivo and the latter technique uses
      freeze trapping and low-temperature fluorescence imaging. The heart is snap
      frozen while still in the chest cavity to make a "snapshot" of the metabolic
      state of the tissue. After freezing, the ischemic area and its surrounding border
      zone were excised and the sample was embedded in a frozen buffer for
      cryoscanning. These two data sets, in vivo fluorometry and low-temperature redox
      scanning, show consistent extreme oxidation of the mitochondrial redox states
      (higher redox ratio) suggesting the initiation of apoptosis following
      reperfusion. This represents the first attempt to assess myocyte apoptosis in the
      beating heart.

PMID- 17212565
TI  - A retrospective controlled analysis of outcomes of using integrated therapy of
      traditional Chinese and modern medicines for primary liver cancer of middle and
      late stages.

PMID- 17212566
TI  - Controversies in acupuncture research: selection of controls and outcome measures
      in acupuncture clinical trials.

PMID- 17212567
TI  - Effects of a color filter used in auriculomedicine on ultraweak photon emission
      of the human body.
AB  - CONTEXT: The human body emits ultraweak photons. It has been demonstrated that
      feedback regulation of ultraweak photon emission from the hand is detectable
      utilizing gelatin color filters in complete darkness. Color filters are commonly
      utilized in auriculomedicine diagnostic procedures based on the radial artery
      vascular autonomic signal. OBJECTIVE: To evaluate the possibility of an effect by
      a dark-adapted red filter on (1) local ultraweak human photon emission using
      different anatomic locations, and (2) on systemic photon emission using one
      location for red filter exposure and another for photon emission recording.
      DESIGN: Photon emission of abdomen, forehead, palm, and dorsum of the hand was
      recorded before and after the presence of a red filter. In addition, photon
      emission of forehead and dorsum of the hand was recorded before, during, and
      after the presence of the red filter close to the palm. In both instances, the
      filter was dark-adapted and placed in close proximity to, but not touching the
      skin of the dark-adapted subject. A low-noise, end window photomultiplier for
      recording ultraviolet and visible (200-650 nm) photon emission (with a very low
      background count rate) and designed for manipulation in three directions was
      situated in a dark room. The technology was utilized to record spontaneous photon
      emission of the abdomen, forehead, palm, and dorsum of the hand of one human male
      subject. RESULTS: Data demonstrate that a dark-adapted subject responds in the
      total absence of light with a temporary increase in photon emission from the
      anatomic locations that had been exposed for 200 s at a distance of 3 cm to a
      dark-adapted red filter. Data from sequential time series suggest red filter
      initiation of a refractory emission reaction. Exposure of the palm to the red
      filter also evokes photon emission from the dorsum of the same hand and from the
      forehead. This response could be registered immediately after the beginning of
      the exposure. The stimulated emission is followed by a slow decrease of emission
      in the period after exposure to the filter. CONCLUSION: Data suggest that red
      filter-stimulated photon emission response is systemic and rapid. Data imply an
      exchange of information vis-a-vis light from both hand and red filter. The
      mechanism of such interaction is currently speculation only.

PMID- 17212568
TI  - Electroacupuncture for refractory acute emesis caused by chemotherapy.
AB  - PURPOSE: To evaluate the efficacy of electroacupuncture in preventing
      anthracycline-based chemotherapy-related nausea and emesis refractory to
      combination 5HT(3)-antagonist and dexamethasone. PATIENTS AND METHODS: Cancer
      patients with refractory emesis after their first cycle of doxorubicin-based
      chemotherapy were accrued into this study. Electroacupuncture was given during
      the second cycle of chemotherapy. Each patient was evaluated for the number of
      emetic episodes and grade of nausea within the first 24 hours after chemotherapy
      and electroacupuncture. RESULTS: Forty-seven of a total of 317 patients screened
      were eligible for this study. Of these, 27 patients agreed to participate. Twenty
      six (26; 96.3%) of them had significant reduction in both nausea grade and
      episodes of vomiting after electroacupuncture. There was complete response with
      no emetic episodes in 37%. Subjectively, 25 (92.6%) of the total 27 patients
      believed that acupuncture was an acceptable procedure and was helpful in reducing
      emesis. Electroacupuncture was well-tolerated with a median pain score of 3 of
      10. CONCLUSION: Electroacupuncture is well-tolerated and effective as an adjunct
      in reducing chemotherapy-related nausea and emesis.

PMID- 17212569
TI  - Trial of Essiac to ascertain its effect in women with breast cancer (TEA-BC).
AB  - BACKGROUND: Breast cancer is a major cause of morbidity, mortality, and medical
      expenditures among women in Canada. Essiac (Resperin Canada Limited, Waterloo,
      Ontario, Canada), a blend of at least four herbs (burdock root [Arctium lappa],
      Indian rhubarb [Rheum palmatum], sheep sorrel [Rumex acetosella], and the inner
      bark of slippery elm [Ulmus fulva or U. rubra]), has become one of the more
      popular herbal remedies for breast-cancer treatment, secondary prevention,
      improving quality of life, and controlling negative side-effects of conventional
      breast-cancer treatment. OBJECTIVES: Our primary objective was to determine the
      difference in health-related quality of life (HR-QOL), as assessed by the
      Functional Assessment of Cancer Therapy Breast Cancer Version, between women who
      are new Essiac users (since breast cancer diagnosis) and those who have never
      used Essiac. Secondary endpoints included differences in depression, anxiety,
      fatigue, rate of adverse events, and prevalence of complications or benefits
      associated with Essiac during standard breast-cancer treatment. Additionally, we
      described the pattern of use of Essiac in this cohort of women. METHODS: We
      performed a retrospective cohort study in 510 women, randomly chosen from the
      Ontario Cancer Tumour Registry, with a diagnosis of primary breast cancer in
      2003. RESULTS: With the exception changes in a Physical well-being subscale and a
      relationship with doctor subscale, Essiac did not have a significant effect on HR
      QOL or mood states. Even for Physical well-being and relationship with doctor,
      Essiac seemed to have a negative effect, with Essiac users doing worse than the
      non-Essiac users. This might be attributed to the fact that the group of users
      comprised younger women with more advanced stages of breast cancer, and both of
      these subgroups of patients have been shown to be at a significantly increased
      risk for negative mood states and/or a decreased sense of well-being. The women
      were taking low doses (total daily dose 43.6 +/- 30.8 mL) of Essiac that
      corresponded to the label directions found on most Essiac products. Friends were
      the most common source of information, and most women were taking Essiac to boost
      their immune systems or increase their chances of survival. Only 2 women reported
      minor adverse events, whereas numerous women reported beneficial effects of
      Essiac. CONCLUSIONS: Essiac does not appear to improve HR-QOL or mood states.
      Future studies are needed to determine whether other clinical outcomes, such as
      cancer reoccurrence, are affected by Essiac.

PMID- 17212570
TI  - Devil's Claw (Harpagophytum procumbens) as a treatment for osteoarthritis: a
      review of efficacy and safety.
AB  - BACKGROUND: Osteoarthritis (OA) is a highly prevalent musculoskeletal disorder.
      Conventional treatment (i.e., the use of nonsteroidal anti-inflammatory drugs
      NSAIDs) is associated with well-documented adverse effects. Devil's Claw
      (Harpagophytum procumbens) a traditional South African herbal remedy used for
      rheumatic conditions, may be a safer treatment option. To date, 14 clinical
      trials have assessed its efficacy/ effectiveness in OA. AIM: To address the two
      main questions of importance to clinicians: (1) Does Devil's Claw work for the
      treatment of OA, and (2) Is it safe? METHODS: A review of the literature on
      Devil's Claw and OA from 1966 to 2006 was performed using multiple search
      databases, monographs, and citation tracking. Relevant trials in all languages
      were identified and included. Both internal validity (i.e., adequacy of the
      dosage and period of treatment for this condition, reporting of randomization,
      rates of dropout, blinding, and statistical analysis) and external validity
      (i.e., inclusion/ exclusion criteria, baseline characteristics of the study
      populations, trial setting, and the appropriateness of the outcome measures of
      the trials) were assessed. RESULTS: Fourteen studies were identified: eight
      observational studies; 2 comparator trials (1 open, the other randomized to
      assess clinical effectiveness); and 4 double-blinded, placebo-controlled,
      randomized controlled trials to assess efficacy. Many of the published trials
      lacked certain important methodological quality criteria. However, the data from
      the higher quality studies suggest that Devil's Claw appeared effective in the
      reduction of the main clinical symptom of pain. The assessment of safety is
      limited by the small populations generally evaluated in the clinical studies.
      From the current data, Devil's Claw appears to be associated with minor risk
      (relative to NSAIDs), but further long-term assessment is required. CONCLUSIONS:
      The methodological quality of the existing clinical trials is generally poor, and
      although they provide some support, there are a considerable number of
      methodologic caveats that make further clinical investigations warranted. The
      clinical evidence to date cannot provide a definitive answer to the two questions
      posed: (1) Does it work? And (2) is it safe? A definitive high-quality trial that
      addresses the necessary methodologic improvements noted is needed to answer these
      important clinical questions.

PMID- 17212571
TI  - Comprehensive, integrative management of pain for patients with sickle-cell
      disease.
AB  - PURPOSES: The study was conducted to: (1) investigate both pharmacologic and
      complementary therapies used for pain management by caregivers of children with
      sickle cell disease (SCD), (2) investigate the prevalence and types of
      complementary therapies used for pain management by caregivers of children with
      SCD, and (3) explore caregivers' interests in using complementary therapies in
      the future. METHODS: A cross-sectional, descriptive design was used. Sixty-three
      caregivers of children with SCD were asked to complete a questionnaire while they
      visited a SCD clinic. Chi-square tests were performed to compare demographic
      variables, examine use of pharmacologic therapies for pain management between age
      groups, and compare use of pharmacologic and complementary therapies. RESULTS:
      The most frequently used pain medications for children with SCD (mean age 9
      years) were ibuprofen (37.5%), acetaminophen with codeine (32.1%), and
      acetaminophen with oxycodone (14.5%). More than 70% of 63 caregivers (mean age 33
      years) were using some form of complementary therapies (3.67 +/- 2.95, range: 0
      9) for their child. The most commonly used therapies were prayer, spiritual
      healing by others, massage, and relaxation. Complementary therapy use was
      significantly higher among caregivers of children who were taking two or more
      analgesics compared to children taking no analgesics or one analgesic (chi (2) =
      3.954, p = 0.047). Although no difference was found in nonopioid analgesic use,
      there was significant difference in opioid analgesic use (chi (2) = 14.736, p =
      0.002) and total medication use (chi (2) = 11.025, p = 0.012) between children <
      or = 12 years and > or =13 years. CONCLUSIONS: Caregivers of children using
      greater numbers of conventional pain medications were more likely to be using
      complementary therapies as well. If offered in the future, many caregivers were
      willing to try various types of complementary therapies for pain management.

PMID- 17212572
TI  - Complementary and alternative medicine use among Asian-American subgroups:
      prevalence, predictors, and lack of relationship to acculturation and access to
      conventional health care.
AB  - OBJECTIVES: Acculturation and access to conventional health care have been found
      to be predictors of complementary and alternative medicine (CAM) use in the
      general population. We hypothesized that these factors would be predictors of CAM
      use in Asian-American subgroups. Because of differences in health and cultural
      beliefs, we also hypothesized that patterns and predictors of CAM use would vary
      among Asian-American subgroups. METHODS: Cross-sectional survey of a sample of
      9187 adults representative of the California population. RESULTS: Nearly three
      quarters of Asian-Americans used at least one type of CAM in the past 12 months,
      which was significantly higher than the national prevalence rate. Chinese
      Americans had the highest prevalence of any CAM use, whereas South Asians had the
      lowest prevalence (86% vs. 67%, respectively). Acculturation and access to
      conventional medical care was unrelated to any CAM use for most Asian-American
      subgroups. Spirituality was the strongest predictor of any CAM use for most Asian
      American subgroups. CONCLUSIONS: CAM use varies across Asian-American subgroups.
      Acculturation and access to conventional medical care is unrelated to any CAM use
      for most Asian-American subgroups.

PMID- 17212573
TI  - Acquired long QT syndrome secondary to cesium chloride supplement.
AB  - The use of complementary medication is on the rise worldwide. More often than
      not, the treating physicians are unaware of this and also unfamiliar with the
      potential benefit or toxicity of the agents. Here, we present the case of a 39
      year-old woman who presented with new onset of syncope as a result of acquired
      long QT syndrome secondary to taking a cesium chloride supplement. A brief
      discussion of the pathophysiology of this agent follows the case presentation.

PMID- 17212574
TI  - Human psychophysiology, macroscopic information entanglement, and the placebo
      effect.
AB  - For the past 20 years, the magnitude of the "placebo effect" in double-blind,
      medical experiments has strongly increased. This paper asks why and how. Starting
      with the human "psychophysiologic principle," two unconscious and one conscious
      biofeedback examples are given to demonstrate how malleable we humans are to our
      expectations and our intentions and how strong our psychoenergetic forces can be
      relative to conventional chemical forces. Ending with several experimental
      examples wherein a therapeutically processed device and an unprocessed device are
      critically compared, one finds strong evidence to propose that an information
      entanglement process is converting the unprocessed device to a functional replica
      of the processed device in that its therapeutic efficacy is comparable to that of
      the treatment device. Furthermore, arguments are provided to indicate that a
      practitioner's biofield is capable of expanding the range of diagnostic
      capability of commercial measurement instruments so that the practitioner/device
      hybrid system becomes a potent psychoenergetic instrument for diagnostic and
      treatment purposes. In between, a theoretical model is provided, based on the
      author's extensive experimental psychoenergetic research on long-range
      interconnectivity between objects, between humans and between humans and objects,
      to show how long-range, quantitative coupling can occur between our normal
      atom/molecule level of physical reality and a second, unique level of physical
      reality whose physics can be modulated by psychoenergetic forces. It is the
      material qualities of this duplex physical reality that convert a seemingly inert
      object/device (placebo) into a synergistically active element in double-blind
      placebo experiments.

PMID- 17212575
TI  - Illness: an opportunity for spiritual growth.
AB  - Spirituality is an innate aspect of being human, and every patient has the
      potential for spiritual growth through suffering from an illness. However,
      spirituality and spiritual care are rarely mentioned in the field of medicine,
      either because their definition can be ambiguous or because their nature can be
      highly personal. In a departure from the traditional biomedical view of health
      care, the author in this paper explores another aspect of the patient, hoping to
      inspire caregivers to be more attentive to the growth of a patient's
      spirituality. Furthermore, citing several clinical examples and by extrapolating
      the trajectory of human adaptation to illness, the author also delineates the
      proper compass of spiritual care and uncovers the distinction between
      spirituality, religion, and psyche.

PMID- 17212576
TI  - Policy for therapeutic acupuncture in an academic health center: a model for
      standard policy development.
AB  - Acupuncture as a therapeutic modality offers multiple applications. Its
      effectiveness coupled with its general acceptance by conventional health care
      professionals makes it one of the first complementary and alternative medicine
      (CAM) modalities to be incorporated in an integrative approach to care. However,
      few centers that offer acupuncture have written standard policies to regulate its
      use. This lack of standard policies may impede provision of quality care, serve
      as a barrier to cross-institutional data collection and clinical application of
      that data, and may put health care professionals and institutions at risk when
      credentialing or malpractice liability has not been clearly addressed. Here we
      present a policy for acupuncture, created by a diverse group of health care
      professionals at the University of Michigan Health System. It may function as a
      generalizable template for standard policy development by institutions
      incorporating acupuncture.

PMID- 17212578
TI  - Cracking the mild, difficult and fiendish codes within and downstream of the EGFR
      to link diagnostics and therapeutics.
AB  - Over the last 45 years, I have been working on growth factors, their receptors
      and signal transduction mechanisms. This period has seen a tremendous growth in
      knowledge and technology, and all of this, together with a focus interest in
      oncology, has steered me along a path designed to understand growth factor
      signalling so that we can see how drugs that target signalling pathways might be
      able to control cancer. The knowledge that we already have is likely to lead to
      cures for many common cancers within the next 25 years.

PMID- 17212579
TI  - Protein kinases and their therapeutic exploitation.
AB  - This review focuses on the recognition properties of protein kinases at the
      molecular level. Phosphorylation of the substrate protein by a protein kinase can
      result in enzyme activation or inhibition, conformational changes that change
      recognition properties, or the creation of a surface with distinct binding
      properties. Protein kinases have become important targets for the development of
      inhibitors with potential therapeutic application. Various examples are
      considered in this review, and I discuss our own work on glycogen phosphorylase
      and phosphorylase kinase, and the structures of proteins involved with the cell
      cycle, including cyclins and cyclin-dependent kinases.

PMID- 17212580
TI  - Functions of the proteasome: from protein degradation and immune surveillance to
      cancer therapy.
AB  - This review focuses on recent insights into the mechanisms and the biological
      functions of the proteasome. This large ATP-dependent proteolytic complex is the
      main site for protein degradation in mammalian cells and catalyses the rapid
      degradation of ubiquitinated proteins, and is the source of most antigenic
      peptides used by the immune system to screen for viruses and cancer. ATP is
      required to unfold globular proteins to open the gated channel into the 20S
      proteasome and to facilitate protein translation into it. Inhibitors of its
      proteolytic activity are widely used as research tools and have proven effective
      in cancer therapy.

PMID- 17212581
TI  - Modelling molecular mechanisms of breast cancer and invasion: lessons from the
      normal gland.
AB  - The interplay between genes and environment is complex, particularly when it
      comes to cancer. Studies on breast cancer cells have shown that environmental
      influences dominate over genotype in their effect on phenotype, and can cause
      cancerous cells to revert to a non-malignant phenotype, while remaining
      genotypically malignant. Using breast tissue in three-dimensional cell culture
      has proved a better model than traditional two-dimensional cell culture in that
      different cell types can be seen to behave differently to the same pro-apoptotic
      signal, with normal cells surviving.

PMID- 17212582
TI  - G-protein-coupled receptor signalling through protein networks.
AB  - This short review provides a broad, and therefore necessarily incomplete and
      personal, overview of G-protein-coupled receptors, which are often targets for a
      wide range of important drugs: I will discuss successively their structure,
      function and interactions with associated proteins. Examples will be drawn from
      work done over the last 30 years by scientists that worked at different times in
      my laboratories, mainly in the field of beta-adrenoceptors, muscarinic
      acetylcholine, melatonin and angiotensin receptors.

PMID- 17212583
TI  - Exploring the role of protein phosphorylation in plants: from signalling to
      metabolism.
AB  - This review presents a broad overview of phosphorylation and signalling in
      plants. Much of the work of my group in plants focuses on understanding the
      mechanisms that regulate the production of carbon and nitrogen metabolites in
      leaves; in this review, I will discuss nitrate, which is one of the most
      important of these inorganic nutrients. I also detail how protein phosphorylation
      in plant cells is altered in response to the presence of reactive oxygen species.

PMID- 17212584
TI  - Human obesity and insulin resistance: lessons from experiments of nature.
AB  - Examination of individuals with 'extreme phenotypes' has revealed some rare
      monogenic disorders that were previously unknown. This identification can shed
      light on physiological pathways that are also important in normal physiology and
      how their impairment leads to more common, milder, multigenic forms of the
      disease. Ultimately, this is a potential route to treatment of both disease
      types. This approach is discussed in relation to Type 2 diabetes, arising from
      both insufficient insulin production and insulin resistance.

PMID- 17212585
TI  - The public's belief about biology.
AB  - This short review is concerned with a topic that has been neglected and is still
      very poorly understood: what the general public think and believe about biology
      (including health and medicine, and bioethics), and, in particular, about
      biotechnology.

PMID- 17212586
TI  - Presence of tumour inhibits the normal post-operative response in arginine and NO
      production in non-cachectic mice.
AB  - We have described recently that cancer patients have low plasma arginine
      concentrations, even without weight loss being present, suggesting that decreased
      arginine availability may be a specific feature of the presence of tumour. As
      arginine is important in post-operative repair, we hypothesized that
      abnormalities in arginine metabolism in cancer lead to an aberrant post-operative
      response in arginine and NO metabolism. To investigate this, we studied post
      operative alterations in arginine and NO production and the acute-phase response
      in MCA (methylcholanthrene) sarcoma-bearing mice. Controls, mice with small MCA
      tumours (<15% of carcass weight) and large MCA tumours (>15% of carcass weight)
      were studied, either with or without undergoing laparotomy. The stable isotopes L
      [guanidino-(15)N(2)-(2)H(2)]arginine and L-[ureido-(15)N]citrulline were used to
      study whole-body arginine and NO production rates. SAP (serum amyloid P
      component) concentrations were measured to assess the acute-phase response.
      Significance was tested using Mann-Whitney U test. In healthy FVB mice,
      laparotomy significantly increased whole-body arginine production (from 42+/-3 to
      54+/-3 nmol x 10 g(-1) of carcass weight x min(-1)), NO production (from 1.1+/
      0.1 to 1.4+/-0.2 nmol x 10 g(-1) of carcass weight x min(-1)) and levels of SAP
      (from 4+/-1 to 115+/-23 ng/ml), whereas in all MCA tumour-bearing mice baseline
      values of arginine metabolism and SAP concentration were already elevated and the
      response to laparotomy was absent. In conclusion, MCA tumour-bearing mice had a
      disturbed post-operative metabolic response, as evidenced by attenuated post
      operative arginine and NO production, concomitant with an attenuated acute-phase
      response. This indicates that altered arginine metabolism may be an important
      characteristic of the metabolic changes in cancer.

PMID- 17212587
TI  - Interference with energy metabolism by 5-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside induces HPV suppression in cervical carcinoma cells and apoptosis
      in the absence of LKB1.
AB  - Carcinogenesis is a dynamic and stepwise process, which is accompanied by a
      variety of somatic and epigenetic alterations in response to a changing
      microenvironment. Hypoxic conditions will select for cells that have adjusted
      their metabolic profile and can maintain proliferation by successfully competing
      for scarce nutritional and oxygen resources. In the present study we have
      investigated the effects of energy depletion in the context of HPV (human
      papillomavirus)-induced pathogenesis. We show that cervical carcinoma cell lines
      are susceptible to undergoing either growth arrest or cell death under conditions
      of metabolic stress induced by AICAR (5-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside), a known activator of the AMPK (AMP-activated protein kinase).
      Our results reveal that AICAR treatment leads to a reduced binding affinity of
      the transcription factor AP-1 (activator protein-1) and in turn to a selective
      suppression of HPV transcription. Moreover, the outcome of AICAR on proliferation
      and survival was dependent on p53 activation and the presence of LKB1, the major
      upstream kinase of AMPK. Using non-malignant LKB1-expressing somatic cell
      hybrids, which lose expression after tumorigenic segregation, as well as small
      interfering RNA LKB1 knockdown approaches, we could further demonstrate that
      expression of LKB1 protects cells from cytotoxicity induced by agents which
      modulate the ATP/AMP ratio. Since simulation of low energy status can selectively
      eradicate LKB1-negative cervical carcinoma cells, AICAR may represent a novel
      drug in the treatment of cervical cancer.

PMID- 17212588
TI  - Mitosis-specific MPM-2 phosphorylation of DNA topoisomerase IIalpha is regulated
      directly by protein phosphatase 2A.
AB  - Recent results suggest a role for topoIIalpha (topoisomerase IIalpha) in the fine
      tuning of mitotic entry. Mitotic entry is accompanied by the formation of
      specific phosphoepitopes such as MPM-2 (mitotic protein monoclonal 2) that are
      believed to control mitotic processes. Surprisingly, the MPM-2 kinase of
      topoIIalpha was identified as protein kinase CK2, otherwise known as a
      constitutive interphase kinase. This suggested the existence of alternative
      pathways for the creation of mitotic phosphoepitopes, different from the
      classical pathway where the substrate is phosphorylated by a mitotic kinase. In
      the present paper, we report that topoIIalpha is co-localized with both CK2 and
      PP2A (protein phosphatase 2A) during interphase. Simultaneous incubation of
      purified topoIIalpha with CK2 and PP2A had minimal influence on the total
      phosphorylation levels of topoIIalpha, but resulted in complete disappearance of
      the MPM-2 phosphoepitope owing to opposite sequence preferences of CK2 and PP2A.
      Accordingly, short-term exposure of interphase cells to okadaic acid, a selective
      PP2A inhibitor, was accompanied by the specific appearance of the MPM-2
      phosphoepitope on topoIIalpha. During early mitosis, PP2A was translocated from
      the nucleus, while CK2 remained in the nucleus until pro-metaphase thus
      permitting the formation of the MPM-2 phosphoepitope. These results underline the
      importance of protein phosphatases as an alternative way of creating cell-cycle
      specific phosphoepitopes.

PMID- 17212589
TI  - Allosteric activation of the extracellular Ca2+-sensing receptor by L-amino acids
      enhances ERK1/2 phosphorylation.
AB  - The calcium-sensing receptor (CaR) mediates feedback control of Ca2+o
      (extracellular Ca2+) concentration. Although the mechanisms are not fully
      understood, the CaR couples to several important intracellular signalling
      enzymes, including PI-PLC (phosphoinositide-specific phospholipase C), leading to
      Ca2+i (intracellular Ca2+) mobilization, and ERK1/2 (extracellular-signal
      regulated kinase 1/2). In addition to Ca2+o, the CaR is activated allosterically
      by several subclasses of L-amino acids, including the aromatics L-phenylalanine
      and L-tryptophan. These amino acids enhance the Ca2+o-sensitivity of Ca2+i
      mobilization in CaR-expressing HEK-293 (human embryonic kidney) cells and normal
      human parathyroid cells. Furthermore, on a background of a physiological fasting
      serum L-amino acid mixture, they induce a small, but physiologically significant,
      enhancement of Ca2+o-dependent suppression of PTH (parathyroid hormone)
      secretion. The impact of amino acids on CaR-stimulated ERK1/2, however, has not
      been determined. In the present study, we examined the effects of L-amino acids
      on Ca2+o-stimulated ERK1/2 phosphorylation as determined by Western blotting and
      a newly developed quantitative assay (SureFire). L-Amino acids induced a small,
      but significant, enhancement of Ca2+o-stimulated ERK1/2. In CaR-expressing HEK
      293 cells, 10 mM L-phenylalanine lowered the EC50 for Ca2+o from approx. 2.3 to
      2.0 mM in the Western blot assay and from 3.4 to 2.9 mM in the SureFire assay.
      The effect was stereoselective (L>D), and another aromatic amino acid, L
      tryptophan, was also effective. The effects of amino acids were investigated
      further in HEK-293 cells that expressed the CaR mutant S169T. L-Phenylalanine
      normalized the EC50 for Ca2+o-stimulated Ca2+i mobilization from approx. 12 mM to
      5.0 mM and ERK1/2 phosphorylation from approx. 4.6 mM to 2.6 mM. Taken together,
      the data indicate that L-phenylalanine and other amino acids enhance the Ca2+o
      sensitivity of CaR-stimulated ERK1/2 phosphorylation; however, the effect is
      comparatively small and operates in the form of a fine-tuning mechanism.

PMID- 17212590
TI  - Heat-shock-induced three-dimensional-like proliferation of mouse fibroblasts
      mediated by hydroxyapatite.
AB  - The aim of the present study was to determine both the minimal and the optimal
      conditions under which heat treatment is effective for enhancing 3D (three
      dimensional)-like cell proliferation. C3H10T1/2 mouse fibroblasts were cultured
      with hydroxyapatite granules for 10 weeks after heat treatment at 40, 41.5, 43,
      44 or 45 degrees C for 2, 10, 15, 20, 30, 45, 60, 90, 180 and 360 min. Then
      minimal and optimal conditions of temperature and duration of heat treatment for
      induction of 3D-like proliferation of cells were determined. The minimal
      conditions of heat treatment to induce 3D-like proliferation were 43 degrees C
      for 2 min and the optimal conditions were 43 degrees C for 10 min. The mean rates
      of formation of 3D-like proliferation patterns by cells heat-treated at 43
      degrees C for 2 and 10 min were significantly higher (1.7- and 3.7-fold
      respectively) than that by untreated cells (P<0.05). We also observed
      significantly greater effects of heat treatment on 3D-like proliferation at 40
      degrees C for 90 or 180 min and at 41.5 degrees C for 15 min and 44 degrees C for
      10 min. We found that apoptosis had occurred in 7.5 and 87.0% of the cells at 1
      week after heat treatment at 43 degrees C for 10 min and 30 min respectively.
      Western-blot analysis demonstrated that phosphorylation of p38 MAPK (mitogen
      activated protein kinase) was markedly increased by heat treatment at 43 degrees
      C for 10 min. These findings suggest that activation of p38 MAPK by heat shock is
      associated with 3D-like cell proliferation. The results of the present study
      should be useful for further studies aimed at elucidation of the physiological
      mechanisms underlying thermotherapy and hyperthermia.

PMID- 17212592
TI  - BibA: a novel immunogenic bacterial adhesin contributing to group B Streptococcus
      survival in human blood.
AB  - By the analysis of the recently sequenced genomes of Group B Streptococcus (GBS)
      we have identified a novel immunogenic adhesin with anti-phagocytic activity,
      named BibA. The bibA gene is present in 100% of the 24 GBS strains analysed. BibA
      specific IgG were found in human sera from normal healthy donors. The putative
      protein product is a polypeptide of 630 amino acids containing a helix-rich N
      terminal domain, a proline-rich region and a canonical LPXTG cell wall-anchoring
      domain. BibA is expressed on the surface of several GBS strains, but is also
      recovered in GBS culture supernatants. BibA specifically binds to human C4
      binding protein, a regulator of the classic complement pathway. Deletion of the
      bibA gene severely reduced the capacity of GBS to survive in human blood and to
      resist opsonophagocytic killing by human neutrophils. In addition, BibA
      expression increased the virulence of GBS in a mouse infection model. The role of
      BibA in GBS adhesion was demonstrated by the impaired ability of a bibA knockout
      mutant strain to adhere to both human cervical and lung epithelial cells.
      Furthermore, we calculated that recombinant BibA bound to human epithelial cells
      of distinct origin with an affinity constant of approximately 10(-8) M for
      cervical epithelial cells. Hence BibA is a novel multifunctional protein involved
      in both resistance to phagocytic killing and adhesion to host cells. The
      identification of this potential new virulence factor represents an important
      step in the development of strategies to combat GBS-associated infections.

PMID- 17212593
TI  - Biventricular pacing in patients with right ventricular pacing-induced heart
      failure.

PMID- 17212594
TI  - Accuracy of intracardiac echocardiography for assessing the esophageal course
      along the posterior left atrium: a comparison to magnetic resonance imaging.
AB  - BACKGROUND: Atrioesophageal fistula is a potentially fatal complication of
      ablation in the left atrium (LA) to treat atrial fibrillation. OBJECTIVE: The
      objective of our study was to systematically evaluate the diagnostic potential of
      intracardiac echocardiography (ICE) for accurately assessing the esophageal
      course along the posterior LA. METHODS: Thirty-five patients underwent magnetic
      resonance imaging (MRI) before and ICE during pulmonary vein (PV) isolation to
      visualize the esophagus. The location of the esophagus was determined in relation
      to the PVs and anatomic regions of the LA by both ICE and MRI. Using the MRI
      images as a reference, the accuracy of ICE localization was assessed. RESULTS:
      The most common location for the esophagus to appear was the mid-posterior wall
      (80% of patients by ICE, 71% of patients by MRI), followed by the left posterior
      wall (71% of patients by ICE, 63% of patients by MRI) and the right posterior
      wall (60% of patients by ICE, 51% of patients by MRI). The esophagus was seen to
      course near the left PV antrums (left superior PV antrum 34% of patients by ICE
      and MRI; left inferior PV antrum 34% of patients by ICE, 37% of patients by MRI),
      left superior PV (17% of patients by ICE, 20% of patients by MRI), left inferior
      PV (17% of patients by ICE and MRI), right inferior PV antrum (29% of patients by
      ICE, 37% of patients by MRI) and the right inferior PV (3% of patients by ICE,
      17% of patients by MRI). The sensitivity for esophageal location by ICE compared
      to that by MRI ranged between 33% (right inferior PV) and 92% (left superior PV
      antrum, left inferior PV antrum, and mid-posterior wall). The specificity for
      esophageal location by ICE compared to that by MRI ranged between 60% (mid
      posterior wall) and 100% (right inferior PV). The positive predictive value
      ranged between 80% (left inferior PV) and 100% (right inferior PV). The negative
      predictive value ranged between 84% (right inferior PV antrum) and 96% (left
      superior PV antrum). CONCLUSION: Phased array ICE provides rapid, real-time
      localization of the esophagus during LA ablation that is comparable to MRI.

PMID- 17212595
TI  - L-type calcium current reactivation contributes to arrhythmogenesis associated
      with action potential triangulation.
AB  - INTRODUCTION: The morphology of the mammalian cardiac action potential (AP) is an
      important factor in the susceptibility to drug-induced early afterdepolarizations
      (EADs) that may initiate torsade de pointes (TdP). AP triangulation has been
      shown to be an important predictor of drug-induced TdP. METHODS AND RESULTS: APs
      from guinea pig and rabbit left ventricular single myocytes were recorded using a
      microelectrode-recording technique. I(Ca-L) currents were recorded in ventricular
      myocytes of guinea pig and rabbit using patch-clamping technique. At a stimulus
      frequency of 0.5 Hz, guinea pig ventricular myocytes displayed a square-like AP,
      whereas rabbit ventricular myocytes exhibited a triangle-like AP. Dofetilide
      induced EADs were observed only in rabbit ventricular myocytes. Under the guinea
      pig AP clamping condition, the normalized I(Ca-L) instant reactivation currents
      in guinea pig and rabbit myocytes at voltages of -40 mV were 0.13 +/- 0.01 and
      0.14 +/- 0.01, respectively. However, when rabbit AP served as the first clamping
      voltage, the normalized I(Ca-L) reactivation currents at -40 mV in guinea pig and
      rabbit myocytes were 0.20 +/- 0.01, 0.21 +/- 0.01, respectively, indicating that
      the I(Ca-L) recovery from inactivation in the rabbit triangular AP condition was
      significantly faster than in the guinea pig square AP condition. Comparison of
      the voltage clamp using the triangular waveform with the square waveform further
      confirmed that triangulation accelerates I(Ca-L) recovery from inactivation.
      CONCLUSIONS: In rabbit ventricular myocardium, AP triangulation accelerates I(Ca
      L) channel recovery from inactivation, leading to instability of the cell
      membrane potential during repolarization, which is capable of initiating TdP.

PMID- 17212596
TI  - Neuropathies in children and adolescents with diabetes: the tip of the iceberg.

PMID- 17212597
TI  - Comparison of conventional and non-invasive techniques for the early
      identification of diabetic neuropathy in children and adolescents with type 1
      diabetes.
AB  - BACKGROUND: Neuropathy is an important complication and contributes to the
      morbidity of diabetes mellitus. The availability of simple and non-invasive tests
      for screening of early diabetic neuropathy (DN) in children with diabetes may
      prevent further progression of this complication. The purpose of this study was
      to compare conventional nerve conduction studies (NCS) with non-invasive
      techniques, including vibration perception thresholds (VPT) and tactile
      perception thresholds (TPT) for the detection of DN in children and adolescents
      with type 1 diabetes. METHODS: Children from the Alberta Children's Hospital
      Diabetes Clinic with at least 5 yr duration of type 1 diabetes underwent detailed
      evaluations, including neurologic exam, NCS, VPT, and TPT testing. Information on
      duration of diabetes, height, and mean glycosylated hemoglobin (A1C) were also
      collected. Descriptive statistics, including Student's t-test and chi-squared
      test, were used for analysis. RESULTS: Seventy-three children (mean age of 13.7+/
      2.6 yr) completed the study. The mean duration of diabetes was 8.1+/-2.6 yr, and
      the mean A1C was 9.0+/-1.0%. Forty-two (57%) children had DN based on NCS. Using
      NCS as a gold standard, the sensitivity and specificity of VPT were 62 and 65%,
      while the sensitivity and specificity of TPT were 19 and 64%, respectively.
      CONCLUSIONS: Subclinical DN is common among children and adolescents with type 1
      diabetes, and there is a need for better metabolic control in this population.
      VPT and TPT may not be adequate screening tools for the detection of DN in
      children.

PMID- 17212598
TI  - The dilemma of the metabolic syndrome in children and adolescents: disease or
      distraction?
AB  - BACKGROUND: The alarming increase of obesity in children occurring globally is
      raising concern about the implications for development, at earlier ages, of
      atherosclerosis and cardiovascular disease and is driving efforts to evaluate and
      predict risk in the young. A major component of this undertaking has been
      directed to adapting for children the criteria described in adults as the
      metabolic syndrome (MS). METHODS: This article briefly examines the status of and
      controversy about definition of the MS in adults and its value, and then it moves
      on to review the descriptions of the MS in the pediatric age group. This is done
      primarily from the point of view of its usefulness to the clinician. The ranges
      of the criteria used by different investigators, the differences in their
      prevalence and their effectiveness in predicting cardiovascular risk are
      discussed. Current information about cardiovascular risk factors in children,
      their progression into adulthood and their correlation with atherosclerosis in
      children and young adults is outlined. Finally, the current information and
      recommendations for treatment, in children, of cardiovascular risk factors
      including those composing the MS are reviewed. CONCLUSIONS: One conclusion is
      that there needs to be consensus about the criteria for defining the MS in
      children if its use as a diagnosis is to be helpful in this age group. A second
      conclusion questions the value of using this syndromic collection of risk factors
      in children rather than concentrating on the risk factors themselves, evaluating
      their importance in early cardiovascular risk and assessing the safety and
      efficacy of intervention in early life.

PMID- 17212599
TI  - The development of an innovative education curriculum for 11-16 yr old children
      with type 1 diabetes mellitus (T1DM).
AB  - BACKGROUND: Evidence-based, structured education is recommended for all people
      with diabetes; tailored to meet their personal needs and learning styles. Adult
      courses exist in the UK but are of limited value for children. The aim of this
      study was to adapt the adult Dose Adjustment For Normal Eating (DAFNE) course to
      design a skills training course, for children aged 11-16 yr, focusing on self
      management skills within an intensive insulin regime. To ensure that the course
      format meets the developmental, intellectual and social needs of children and
      adolescents and is delivered using educationally sound techniques. METHODS:
      Relevant professionals and potential users of the course were involved in
      curriculum design and content in the following ways: (i) The views of 95
      pediatric diabetes specialist nurses were sought through a postal survey; (ii)
      Focus group discussions were conducted with children with type 1 diabetes
      mellitus (T1DM) and their families to contribute to content and design; and (iii)
      Secondary school teachers worked with experienced pediatric diabetes staff
      advising on educational content and teaching format. RESULTS: The developed
      curriculum uses a progressive modular-based structure to improve self-management
      in a variety of medical and social situations. It has clear learning objectives
      and is based on the format of UK schools curricula. Additional support is
      provided through dedicated parent sessions, involvement of friends and the
      provision of a school resource pack. CONCLUSION: Collaborative working between
      health professionals, school teachers and families has resulted in an age
      appropriate curriculum, which employs validated educational techniques. This will
      be refined following pilot courses before formal evaluation in a multicentre
      randomized controlled trial.

PMID- 17212600
TI  - Comprehensive assessment of postischemic vascular reactivity in Hispanic children
      and adults with and without diabetes mellitus.
AB  - BACKGROUND: To examine the whole postischemic hyperemic response period in
      Hispanic children and adults with and without type 2 diabetes mellitus (T2DM) and
      offer insight into the potential adaptive mechanisms involved in the arterial
      response to disturbances in vascular homeostasis. METHODS: Ninety-eight adults
      and 124 children of Hispanics participated in the study. Endothelial function was
      assessed in the brachial artery using high-resolution ultrasonography (HRU). A
      continuous scan was taken for 5 min during the hyperemic response, flow velocity
      (FV) recordings and diameter measurements were obtained, and brachial arterial
      blood flow (BF) was calculated after the cuff deflation. RESULTS: The increment
      in FV during the reactive hyperemic period was higher in obese and in diabetic
      children than in lean healthy children, although the time to reach peak brachial
      artery diameter (BAD) and the per cent increase in peak diameter were comparable
      in all three groups. In subjects with impaired glucose tolerance (IGT), the
      hyperemic peak increase in FV was comparable to those in healthy adults. In
      diabetic patients, the peak increase in BAD as well as the per cent increment in
      the diameter were reduced at 50-60 s after the release of the arm cuff. The time
      to reach the peak increase in diameter also was prolonged in diabetics when
      compared with healthy adults. CONCLUSION: Our study demonstrates clear
      differences in the normal vascular response between healthy children and healthy
      adults and discloses the presence of additional abnormalities in the flow
      mediated vasodilation in diabetic and 'prediabetic' subjects.

PMID- 17212601
TI  - Science and art: in harmony.

PMID- 17212602
TI  - ISPAD Clinical Practice Consensus Guidelines 2006-2007.

PMID- 17212603
TI  - ISPAD Clinical Practice Consensus Guidelines 2006-2007. Definition, epidemiology
      and classification.

PMID- 17212604
TI  - ISPAD Clinical Practice Consensus Guidelines 2006-2007. The diagnosis and
      management of monogenic diabetes in children.

PMID- 17212607
TI  - Kit-positive interstitial cells in the rabbit urethra: structural relationships
      with nerves and smooth muscle.
AB  - OBJECTIVE: To identify interstitial cells (ICs) in the wall of the rabbit urethra
      using antibodies to the Kit receptor, and to examine their location, morphology
      and relationship with nerves and smooth muscle cells (SMCs), as studies of
      enzymatically isolated cells from the rabbit urethra have established that there
      are specialized cells that show spontaneous electrical activity and have
      morphological properties of ICs. MATERIALS AND METHODS: Urethral tissues from
      rabbits were fixed, labelled with antibodies and examined with confocal
      microscopy. Some specimens were embedded in paraffin wax and processed for
      histology. Histological sections from the most proximal third and mid-third
      region of rabbit urethra were stained with Masson's Trichrome to show their
      cellular arrangement. RESULTS: Sections from both regions had outer longitudinal
      and inner circular layers of SM, and a lamina propria containing connective
      tissue and blood vessels; the lumen was lined with urothelial cells. The mid
      third region had a more developed circular SM layer than the most-proximal
      samples, and had extensive inner longitudinal SM bundles in the lamina propria.
      Labelling with anti-Kit revealed immunopositive cells within the wall of the
      rabbit urethra, in the circular and longitudinal layers of the muscularis. Double
      labelling with an antibody to SM myosin showed Kit-positive cells on the boundary
      of the SM bundles, orientated parallel to the axis of the bundles. Others were in
      spaces between the bundles and often made contact with each other. Kit-positive
      cells were either elongated, with several lateral branches, or stellate with
      branches coming from a central soma. Similar cells could be labelled with
      vimentin antibodies. Their relationship with intramural nerves was examined by
      double immunostaining with an anti-neurofilament antibody. There were frequent
      points of contact between Kit-positive cells and nerves, with similar findings in
      specimens double-immunostained with anti-neuronal nitric oxide synthase (nNOS).
      CONCLUSION: Kit-positive ICs were found within the SM layers of the rabbit
      urethra, in association with nerves, on the edge of SM bundles and in the
      interbundle spaces. The contact with nNOS-containing neurones might imply
      participation in the nitrergic inhibitory neurotransmission of the urethra.

PMID- 17212608
TI  - Recovery after stroke: cognition, ADL function and return to work.
AB  - OBJECTIVES: To examine the recovery of cognitive function, activities of daily
      living (ADL) ability and vocational situation after stroke. MATERIALS AND
      METHODS: Subjects below 65 years of age were included. Cognitive function and
      personal and instrumental ADL were assessed at discharge and at 1 year. Pre
      stroke vocational situation was recorded at baseline and at 1 and 3 years after
      discharge. RESULTS: Fifty-eight patients participated. During the first year
      after discharge, cognitive function and ADL ability improved. At 1 year after
      discharge, 83% still had cognitive dysfunction, 20% were dependent in ADL and few
      had returned to work. Only 20% returned to gainful employment 3 years later.
      CONCLUSIONS: There was a recovery of cognition and ADL function after stroke but
      few persons returned to work. Good neurological status was found to be a
      significant factor and recovery of cognitive function a near-significant factor
      for return to work.

PMID- 17212609
TI  - Testing the combination beta-blocker plus topiramate in refractory migraine.
AB  - OBJECTIVE: To test treatment combining a beta-blocker plus topiramate in migraine
      patients previously resistant to the two medications in monotherapy. PATIENTS AND
      METHODS: Those patients who had not responded to a beta-blocker and topiramate
      received combined treatment. RESULTS: Fifty-eight patients (47 women, age 25-76
      years) received the combined treatment. Thirty-three (57%) met criteria for
      chronic migraine/medication overuse headache, 18 (31%) for migraine without aura
      and seven (12%) with aura. Ten (17%) discontinued due to adverse events. Among
      the 48 patients who tolerated the combination, 36 (75%, 62% of the total series)
      showed response (>50% reduction in frequency), while 12 (25%) did not. The number
      of days with headache/month decreased from 15.1 to 6.5 (-57%). Sixteen (44% of
      responders) showed an excellent (>75%) response. Eighteen patients (38%)
      experienced a total of 26 adverse events (mild-moderate). CONCLUSIONS: The
      combination of beta-blocker plus topiramate showed a benefit in around 60% of
      patients who had not previously responded to monotherapy. Adverse events led to
      discontinuation in one out of six patients. From these open results, it seems
      reasonable to recommend this combination, complementary in terms of mechanism of
      action, as a potential strategy in patients with refractory migraine.

PMID- 17212610
TI  - Dynamic F wave study in patients suffering from peripheral arterial occlusive
      disease.
AB  - OBJECTIVE: To prospectively detect significant transient F wave abnormalities
      obtained after exercise in patients with peripheral arterial disease (PAD) and to
      assess the potential diagnostic sensitivity of dynamic F wave study in such a
      context. PATIENTS AND METHODS: A series of 40 electrical stimuli were delivered
      to the peroneal and the posterior tibial nerves of 25 patients with PAD in order
      to obtain F waves at rest and post-exercise. The following variables were
      estimated and the obtained pre- and post-exercise data were compared: F
      persistence, F wave latency, amplitude, duration and F chronodispersion. For each
      nerve studied, the minimum, average and maximum values were calculated.
      Conventional electrophysiological data were also collected pre- and post-exercise
      and the data obtained were also compared. Twenty-five healthy age-, gender- and
      height-matched individuals served as controls. RESULTS: No evidence of
      conventional nerve conduction abnormalities was recorded either pre- or post
      exercise in the group of patients. As regards the peroneal nerve, the
      significantly reduced F wave persistence (P = 0.007) and maximum F wave amplitude
      post- as opposed to pre-exercise (P = 0.05)- were the main findings to emerge.
      The average (P = 0.017) and the minimum duration (P = 0.005) of tibial F waves
      were also significantly increased post- compared with pre-exercise. Insignificant
      differences were observed between pre- and post-exercise neurophysiological and F
      wave values in the group of controls. CONCLUSION: Given the observed absence of
      conventional neurophysiological abnormalities, the detection of dynamic F wave
      changes supports the view of an increased diagnostic sensitivity of this method
      in patients with mild PAD.

PMID- 17212611
TI  - Increased plasma levels of asymmetric dimethylarginine in patients with carotid
      stenosis: no evidence for the role of the common FABP2 A54T gene polymorphism.
AB  - OBJECTIVE: Both asymmetric dimethylarginine (ADMA), which is an inhibitor of
      endothelial nitric oxide synthase and the fatty acid-binding protein 2 (FABP2)
      A54T gene polymorphism have been associated with cerebrovascular disease. The
      objective of the present study was to investigate the role of ADMA and the FABP2
      A54T polymorphism in carotid atherosclerosis. MATERIAL AND METHODS: 54 patients
      with severe carotid stenosis and 54 matched controls without significant carotid
      stenosis were compared. ADMA was analysed with an ELISA method. The FABP2 A54T
      polymorphism was determined with a polymerase chain reaction-restriction fragment
      length polymorphism technique. RESULTS: Patients with carotid stenosis had higher
      ADMA levels (0.76 +/- 0.16 micromol/l) than the controls (0.70 +/- 0.14
      micromol/l, P < 0,01). Allele and genotype frequencies of the FABP2 polymorphism
      did not differ between patients and controls. CONCLUSIONS: ADMA levels in
      subjects with carotid stenosis are increased which emphasize the role of ADMA as
      a novel risk factor for atherosclerosis and future cardiovascular risk. The FABP2
      A54T polymorphism is not associated with severe carotid stenosis.

PMID- 17212612
TI  - Opinion of Belgian neurologists on antiepileptic drugs: Belgian Study on Epilepsy
      Treatment (BESET).
AB  - OBJECTIVES: To describe the choice of treatment in adult patients with epilepsy
      in Belgium, to detect the presence or absence of consensus among neurologists in
      epilepsy treatment, and to analyze the gaps between current guidelines and
      prescriptions. MATERIALS AND METHODS: Hundred Belgian neurologists were
      systematically interviewed between May and June 2003 using a structured
      questionnaire (modified Rand method). RESULTS: Initial monotherapy was the
      preferred treatment strategy. Valproate was the first choice in idiopathic
      generalized epilepsy (IGE) and carbamazepine in focal epilepsy (FE). The new
      antiepileptic drugs (AED) were usually recommended in second-line. However, in
      special treatment situations, they were considered first-line, e.g., lamotrigine
      in case of women of childbearing age. CONCLUSIONS: Neurologists reached consensus
      for most questions on epilepsy treatment. In 2003, monotherapy with valproate and
      carbamazepine was the common treatment strategy in Belgium, whereas lamotrigine
      and to a lesser extent levetiracetam, topiramate, and oxcarbazepine were
      predominantly prescribed in second-line. This is in agreement with the recently
      published UK epilepsy guidelines but not in agreement, however, with the US
      guidelines, that for new onset epilepsy, new and old drugs are equally effective.
      Belgian neurologists, except for some special situations still prefer old drugs
      as first line.

PMID- 17212613
TI  - Selegiline and blood pressure in patients with Parkinson's disease.
AB  - OBJECTIVES: Parkinson's disease (PD) frequently affects both the extrapyramidal
      system and the autonomic nervous system (ANS), the latter also being sometimes
      disturbed by PD medications. Specifically selegiline is known to disturb
      cardiovascular ANS functions and may cause or enhance orthostatic hypotension.
      METHODS: In order to study the effect of the withdrawal of selegiline on the
      regulation of blood pressure (BP) in advanced PD, an orthostatic test was
      performed in 14 PD patients with wearing-off before the morning levodopa dose and
      thereafter repetitively at 1-h intervals for up to 4 h. A Unified Parkinson's
      Disease Rating Scale motor score evaluation was also carried out hourly. The
      tests were repeated after a 4-week selegiline washout period. RESULTS: Selegiline
      withdrawal decreased systolic BP significantly during the on-stage in a supine
      position as well as during the orthostatic test. The initial drop of BP in the
      orthostatic test was significantly smaller after selegiline withdrawal. The heart
      rate remained unaffected.

PMID- 17212614
TI  - Chemokines CXCL10 and CXCL11 in the cerebrospinal fluid of patients with tick
      borne encephalitis.
AB  - OBJECTIVES: The aim of our study was to determine whether cerebrospinal fluid
      (CSF) of patients with tick-borne encephalitis (TBE) contains CXCL10, CXCL11, p40
      subunit of interleukin-12 (IL-12)/IL-23, IL-18 and IL-15. We compared serum and
      CSF concentrations of CXCL10 and analysed the possible concentration gradient of
      this chemokine between the periphery and central nervous system. MATERIALS AND
      METHODS: The study enrolled 19 TBE patients and 10 patients with non-inflammatory
      neurological diseases. RESULTS: CSF of TBE patients contained CXCL10 (median 217
      pg/ml), CXCL11 (8.3 pg/ml), p40 subunit of IL-12/IL-23 (38.9 pg/ml), IL-18 (30.1
      pg/ml) and IL-15 (5.9 pg/ml). CXCL10 in the CSF of TBE patients was higher
      compared with serum (median 62 pg/ml, P < 0.001). CONCLUSION: CSF of TBE patients
      contains CXCL10, CXCL11, p40 subunit of IL-12/IL-23, IL-18 and IL-15. Increased
      CXCL10 concentration in CSF suggests a role for this chemokine in the recruitment
      of CXCR3-expressing T-cells into the CSF of TBE patients.

PMID- 17212615
TI  - RAGE-NF-kappaB pathway activation in response to oxidative stress in
      facioscapulohumeral muscular dystrophy.
AB  - OBJECTIVES: An increased expression of adenine nucleotide translocator (ANT1),
      found in facioscapulohumeral muscular dystrophy (FSHD), is known to lead to a
      decrease in nuclear factor-kappaB (NF-kappaB) DNA binding and to sensitize muscle
      cells to oxidative stress and apoptosis. Receptor for advanced glycation end
      products (RAGE) mediated by NF-kappaB activation is involved in proinflammatory
      pathomechanism and in muscle fiber regeneration in inflammatory myopathies and in
      limb girdle muscular dystrophy. Oxidative stress can stimulate RAGE- NF-kappaB
      pathway. Our purpose was to verify if oxidative stress may induce RAGE- NF-kappaB
      pathway activation in FSHD, contributing to the pathogenesis of such a disease.
      MATERIALS AND METHODS: On muscle samples of eight patients with FSHD, eight
      patients with Duchenne muscular dystrophy and eight normal controls the following
      studies were carried out: immunocytochemistry for activated NF-kappaB;
      electrophoretic mobility shift assay of NF-kappaB DNA binding activity; Western
      blot studies of RAGE and ANT1; hydrogen peroxide (HP), peroxidase and glutathione
      peroxidase (GPx) assays. RESULTS: An increased RAGE and ANT1 expression in FSHD
      with moderate increase of NF-kappaB DNA binding activity was found together with
      an increased production of HP and a reduced activity of peroxidase and GPx.
      CONCLUSIONS: Our data confirm that response to oxidative stress and ANT1
      increased activity are early events in FSHD muscle. The study also reveals that
      the RAGE- NF-kappaB pathway, induced by oxidative stress, is activated
      independently of the presence of a clear histochemical evidence of muscle damage
      in FSHD.

PMID- 17212616
TI  - Isoelectric focusing is superior to immunofixation electrophoresis in diagnosing
      CNS inflammation.
AB  - BACKGROUND: A sensitive method to detect intrathecal IgG production is important
      in diagnosing inflammatory central nervous system (CNS) diseases, including
      multiple sclerosis (MS). OBJECTIVE: To compare cerebrospinal fluid (CSF)
      electrophoresis with isoelectric focusing (IEF), immunofixation-peroxidase
      electrophoresis (IFPE) and high-resolution agarose electrophoresis with protein
      staining (HRAGE). METHODS: Paired serum and CSF samples from 307 consecutive
      patients attending a general neurology clinic were examined with IEF, IFPE and
      HRAGE. Clinical diagnosis was based on review of the patients' medical records
      after an average of 4 years. RESULTS: The sensitivity for detecting any
      inflammatory (autoimmune or infectious) CNS disease (52 patients) was 67% for
      IEF, 50% for IFPE and 29% for HRAGE. The sensitivity for detecting MS (14
      patients) was 93%, 86% and 29% respectively. The sensitivity for detecting
      clinically isolated syndrome (eight patients) was 75%, 25% and 13% respectively.
      The number of oligoclonal bands in IEF was higher in inflammatory than in non
      inflammatory neurological diseases or symptoms, but similar in MS and other
      inflammatory diseases. CONCLUSION: IEF is the method of choice in diagnosing
      intrathecal IgG synthesis.

PMID- 17212617
TI  - Anti-MuSK-positive myasthenia gravis: neuromuscular transmission failure in
      facial and limb muscles.
AB  - The presence of antibodies against muscle-specific receptor tyrosine kinase
      (MuSK) appears to define a subgroup of patients with myasthenia gravis (MG)
      characterized by weakness predominant in bulbar, facial and neck muscles compared
      with anti-acetylcholine receptor (AChR) antibody-positive MG. To investigate the
      patterns and severity of neuromuscular transmission failure in different muscles
      in MuSK-positive MG, we performed single fiber electromyography (SFEMG) in the
      facial (frontalis) and limb (extensor digitorum communis, EDC) muscles in three
      anti-Musk-positive patients, and compared results with those of 11 anti-AChR
      positive patients. Only one of the three MuSK-positive patients had abnormal
      jitter in EDC, but all the three showed clearly increased jitter in the
      frontalis. By contrast, the AChR-positive patients showed similarly abnormal
      jitter for the two muscles. These results suggest that when the diagnosis of anti
      MuSK-positive MG is suspected, SFEMG should be performed in most prominently
      affected muscles.

PMID- 17212618
TI  - Motor neuron disease recovery associated with IV ceftriaxone and anti-Babesia
      therapy.
AB  - This report summarizes what we believe to be the first verifiable case of a
      significant and progressive motor neuron disease (MND) consistent with
      amyotrophic lateral sclerosis that resolved during treatment with i.v.
      ceftriaxone plus oral atovaquone and mefloquine. The rationale for use of these
      antibiotics was (i) positive testing for Borrelia burgdorferi and (ii) red blood
      cell ring forms consistent with Babesia species infection. The patient has
      continued to be free of MND signs and symptoms for 15 months, although some
      symptoms consistent with disseminated Borreliosis remain.

PMID- 17212619
TI  - Topiramate in frontal lobe epilepsy.
AB  - BACKGROUND: Frontal lobe epilepsy (FLE) is a type of epilepsy that is difficult
      to treat and there are few studies about the use of topiramate (TPM). AIM OF THE
      STUDY: To evaluate the efficacy and tolerability of TPM monotherapy in FLE.
      METHODS: The study group consisted of 55 (33 male; 22 female) patients. TPM was
      administered as a first drug (n = 16) or converted after previous treatment (n =
      39). All patients were followed every 3 months for at least 1 year. The patients
      were subdivided into two groups: 'newly diagnosed' patients and 'difficult-to
      treat' patients. RESULTS: Overall, all patients completed the 1-year study. At
      the end of follow-up, 10 patients showed disappearance of seizures and 33
      patients showed improvement in seizure frequency. In particular, among the newly
      diagnosed patients 6/16 patients showed complete cessation of seizures and 5/16
      patients showed very good response; in the other group, 4/39 patients showed
      complete cessation and 4/39 patients showed a very good response. No patients of
      both groups had worsening of seizures. No treatment-limiting adverse events
      associated with TPM were reported. CONCLUSIONS: TPM is effective in newly
      diagnosed patients with FLE; TPM can be considered for the treatment of FLE.

PMID- 17212620
TI  - Home-care programmes for older adults with disabilities in Canada: how can we
      assess the adequacy of services provided compared with the needs of users?
AB  - The need for home care will probably continue to increase over the next decade as
      one response to innovative health practices designed to help people receive
      services at home instead of in institutions. However, there are no data for
      determining whether home-care programmes can meet user needs. The objectives of
      the present study were to describe the functional autonomy profile of the users
      of public home-care programmes in Quebec, Canada, and to compare the level of
      adequacy between required and provided services in public home-care programmes
      for older adults with disabilities. This study was based on a cross-sectional
      design from September to December 2002. The population studied consisted of all
      users of public home-care services in one administrative region in the province
      of Quebec over this 3-month period. Each user was assessed with the Functional
      Autonomy Measurement System (SMAF) and then classified into one of the 14 Iso
      SMAF profiles. The total number of hours of care required was determined using
      the median number of hours of nursing care, personal care and support services
      associated with each profile. For the sake of comparison with the services
      required, the services provided were calculated from an administrative databank
      that included statistics of the time spent by health professionals on caring for
      home-care users. The ratio of hours of services provided to the number of hours
      of services required by home-care users highlights a discrepancy between the
      services provided and user needs. The results of this study show the feasibility
      of describing users of public home-care programmes and the adequacy of services
      provided in relation to user needs. Based on these results, public home-care
      programmes in the province of Quebec appear to be under-funded.

PMID- 17212621
TI  - From retirement village to residential aged care: what older people and their
      families say.
AB  - The majority of older Australians, some of whom live in retirement villages, wish
      to remain living in their own home, receiving care in the community when their
      health and/or other circumstances change. Current statistics show that 3.7% of
      people aged 65 years and over live in a retirement village in Australia. However,
      residential aged care will still be required for some highly dependent members of
      the older population. This qualitative Australian study examined the transition
      into residential care from one form of community housing, the retirement village.
      In-depth interviews with 33 older people and 48 family members were conducted to
      illuminate the key issues and factors which influence the move of older people
      from retirement villages to residential aged care. Analysis of the data revealed
      the move to be influenced by: health-related crises; the creation of doubt as to
      ability to cope in the retirement village; the need for more or different care or
      support services; the desire for independence; assumptions about being able to
      move into the residential aged care facility co-located with the retirement
      village; availability of a place; navigating the system; and desirable aspects of
      a residential aged care facility. The findings of the study provide a description
      of the transition process from the perspectives of those directly affected, and
      contribute to the development of best practice in the provision of support to
      residents living in retirement villages and the community in general.

PMID- 17212622
TI  - Experiences of mental health discrimination in New Zealand.
AB  - Discrimination against people with experience of mental illness is a recognised
      problem, and there is a lack of information in New Zealand regarding the nature
      of this discrimination. The Like Minds, Like Mine project is a New Zealand
      initiative to combat the stigma and discrimination associated with mental
      illness. This paper reports on a study undertaken as part of this initiative, and
      describes the nature of discrimination that people with experience of mental
      illness face in New Zealand. A written survey was undertaken with people with
      experience of mental illness from throughout New Zealand, using a mixture of
      qualitative and quantitative questions. This questionnaire was distributed
      throughout the country in 2003, using a variety of distribution methods, and 785
      responses were received and analysed from people self-identifying as having
      experienced mental illness. Respondents reported discrimination in all areas of
      their lives. The most commonly reported areas were discrimination by friends and
      family (59%), a fear of being discriminated against (46%), and discrimination in
      looking for employment (34%) and mental health services (34%). Discrimination can
      limit the participation of people with experience of mental illness in our
      society. We all need to examine our own attitudes and behaviours and take
      responsibility for discrimination.

PMID- 17212623
TI  - Self-help groups as mutual support: what do carers value?
AB  - The literature suggests that the United Kingdom, in common with Europe, North
      America, Canada and Scandinavia, has seen significant growth in single-issue self
      help/mutual aid groups concerned with health and social care issues since the
      1970s, but there is only ad hoc academic and policy interest in such groups in
      the United Kingdom. This article presents findings from a doctoral study with two
      self-help/mutual aid groups for carers in South-East England. The data are drawn
      from semistructured interviews with 15 active members which explored reasons for
      joining, benefits derived from membership, and perceived differences between
      support gained by membership and their relationship with professionals. Most
      group members had prior experience of voluntary work/activity, which influenced
      their decision to join, often prompted by a failure of the 'usual' support
      network of family/friends to cope or adjust to the carer's needs. Members
      reported personal gains of empathy, emotional information, experiential knowledge
      and practical information, based on a core value of reciprocity through peer
      support. It is this latter benefit that sets apart membership of self-help groups
      from groups supported by professionals who may not appreciate the scope and
      breadth of carers' responsibilities, or of the importance of their relationship
      with the person for whom they care. In this way, self-help groups offered
      additional, but not alternative, 'space' that enabled members to transcend their
      traditional role as a 'carer'. It is concluded that self-help/mutual aid groups,
      based on reciprocal peer support, offer a valuable type of resource in the
      community that is not replicable in professional-client relations. The findings
      have contemporary relevance given the raft of new policies which value the
      experiential knowledge built by both individual and collectives of carers.

PMID- 17212624
TI  - Postnatal care in the community: report of an evaluation of birthing women's
      assessments of a postnatal home-care programme.
AB  - For more than a decade, there has been a strong trend in many Western countries
      to decrease the length of time that women spend in hospital following childbirth.
      The research evidence regarding the consequences of early discharge for mothers
      and babies is mixed. Recent evidence has suggested that early discharge may not
      be randomly distributed across all sociodemographic groups of birthing women, and
      that the structures of home care have an important influence on maternal and
      child outcomes. In the context of decreasing lengths of hospital stay, the aim of
      the present study was to evaluate a new postnatal home support worker introduced
      into a geographically defined catchment area of a metropolitan hospital in South
      Australia. The evaluation included a formative process component to monitor
      recruitment strategies into the programme, as well as summative evaluation of a
      number of projected programme outcomes. The research methods used included
      interviews with antenatal women (n = 20) about their knowledge of and attitudes
      to the programme, and interviews with postnatal women (n = 63) about their
      transition home experience and assessment of the programme. Secondary analysis of
      client satisfaction surveys (n = 163) and aggregate breast-feeding data was also
      conducted. The results concur with previous research findings regarding the
      importance of rest and practical, home-based support in the postnatal period to
      maternal well-being, successful bonding and transition to motherhood. The results
      demonstrate the importance of well-structured home support services to maternal
      satisfaction and maternal well-being through the provision of physical, social
      and emotional care and support in the home.

PMID- 17212625
TI  - Getting out of the house: the challenges mothers face when their children have
      long-term care needs.
AB  - In most industrialised countries, the care needs of those who are sick, disabled
      and frail are increasingly met in peoples' homes. One of the implications of this
      shift in the site of care is that individuals with long-term care needs and their
      family care providers experience social and spatial isolation. Many are
      housebound and most face considerable challenges in getting out of the house.
      This paper illuminates these challenges as they are experienced by mothers of
      children with long-term care needs, and the resulting isolation and disconnection
      that they experience. Eleven semistructured interviews were conducted in two
      regions of Ontario, Canada. Grounded theory informed the analysis of the mothers'
      accounts of their experiences of getting out of the house. The present findings
      are derived from a larger investigation of the meanings and experiences of the
      home as a place of caring for families with children who have long-term care
      needs. Secondary analysis of the data found that three main challenges restricted
      the mothers' abilities to leave their houses. Mothers experienced difficulties
      getting out of the house when they attempted to leave with the child, and when
      the child was left with an alternative care provider. Physical challenges were
      associated with the work and planning required in moving the child's equipment
      and supplies, meticulous planning of the outing within the daily schedule, and
      navigating barriers in the built and natural environments. Social challenges
      reflected the lack of people within the mothers' social network of family and
      friends who have the knowledge and expertise to care for the child. Service
      challenges resulted from the gaps between the policies and practices of paid
      respite, and the conditions that must be satisfied in order for mothers to be
      able and/or willing to leave the house. The authors also examined the reasons why
      some of the mothers worked from home, and the strategies that they used to get
      out of the house for employment. In this paper, the authors discuss each
      challenge, and how it contributes to the mothers' social and spatial isolation.
      The mothers' experiences elucidate the differences between living in a community
      and being part of a community. The consequences of the isolation on mothers'
      daily lives are not recognised in home and community care policy. The suggestions
      that are put forward concerning paid respite have relevance for home and
      community care policy and practice.

PMID- 17212626
TI  - Health needs of prisoners in England and Wales: the implications for prison
      healthcare of gender, age and ethnicity.
AB  - This paper aims to provide evidence of the healthcare needs of prisoners in
      relation to gender, age and ethnicity, drawing from a larger systematic overview
      of the policy and research literature concerning primary care nursing in prisons
      in England and Wales. The literature overview shaped the initial stages of a
      research project funded by the Department of Health to examine the views and
      perspectives of prisoners and nurses working in prisons, and to identify good
      primary care nursing in the prison environment. At total of 17 databases were
      searched using search terms related to primary healthcare in prisons (health,
      nurs*, primary care, healthcare, family medicine, prison*, offender*, inmate*)
      with terms truncated where possible in the different databases. Following this, a
      sifting phase was employed using inclusion/exclusion criteria to narrow and focus
      the literature perceived as relevant to the research questions. All papers were
      critically appraised for quality using standardised tools. Findings from the
      literature overview show that prisoners are more likely to have suffered some
      form of social exclusion compared to the rest of society, and there are
      significantly greater degrees of mental health problems, substance abuse and
      worse physical health in prisoners than in the general population. Women, young
      offenders, older prisoners and those from minority ethnic groups have distinct
      health needs compared to the prison population taken as a whole, with
      implications for the delivery of prison healthcare, and how these needs are met
      effectively and appropriately.

PMID- 17212627
TI  - Battle on the home care front: perceptions of home care workers of factors
      influencing staff retention in Northern Ireland.
AB  - The provision of home care services is a key component in avoiding inappropriate
      admission of older people to institutional care and preventing delayed discharge
      from hospital. However, there is a growing problem of retention of home care
      workers (HCWs), creating problems for delivering this increasingly essential
      service. The present study was based in a health and social services trust in
      Northern Ireland, and was designed to explore the growing problem of retention of
      HCWs from their own perspective. The cross-sectional survey design used a
      convenience sample and questionnaires were completed by 45 HCWs (response rate =
      45 of 147, 31%). Responses to most questions were on five-point ordinal scales.
      Focus groups in which 12 HCWs participated were used to explore emerging themes.
      The variables studied were HCWs' perspectives on: (1) reasons for considering
      leaving; (2) working hours; (3) supervision and support, and qualifications and
      training; (4) workload pressures; (5) client attitudes; (6) pay; and (7) job
      satisfaction. The main reasons given by HCWs for dissatisfaction and considering
      leaving were (in rank order): (1) irregular and antisocial hours; (2) lack of
      management support; and (3) workload pressures. Commitment to caring seemed to be
      the reason why pay did not feature more highly for those who did not leave. Home
      care workers are being required to provide care for people with evermore-complex
      health and social care needs, and in an environment increasingly regulated in
      terms of quality and risk. This makes it an increasingly demanding job, which
      does not seem to be recognised in the training and working conditions of HCWs.
      The most significant factors identified give scope for service managers to
      improve the retention of HCWs.

PMID- 17212628
TI  - The process of health visiting and its contribution to parental support in the
      Starting Well demonstration project.
AB  - Significant resources are being directed at interventions designed to attenuate
      the effects of deprivation on children's health and development. The Starting
      Well demonstration project, established in two deprived areas within a Scottish
      city, aimed to show that a programme of planned activities to support families
      could improve child health. The project was subject to a main quantitative
      evaluation and several additional qualitative and mixed-method evaluations. The
      present paper draws on findings from one of the qualitative studies that sought
      to gain insight into how interventions provided by health visitors were
      operationalised and how they were perceived by parents. The particular focus of
      this paper is how the process of health visiting resulted in parents' perceptions
      of being supported. A longitudinal design captured variation in work undertaken
      by health visitors and temporal changes in maternal experiences of child rearing.
      Semi-structured interviews were conducted with 20 mothers and their health
      visitors at two time points, i.e. when infants were 3-4 and 9-10 months old.
      Sampling was 'purposive', and included first-time and experienced mothers. The
      findings reported here are based on 59 interviews carried out during 2002 and
      2003. The analysis involved a thematic approach focused on programme
      implementation, and participant perceptions about process and benefit. Parental
      perceptions of being supported were exemplified by increased confidence in infant
      care, reduced anxiety regarding infant care needs, increases in knowledge and
      sense of personal competence in parenting practices, reduced isolation, and
      advocacy for those experiencing problems. A selection of the interactional
      processes that resulted in these forms of perceived support are reported,
      including methods of providing information, cautious and tactful questioning of
      maternal decision-making, and encouragement of successful parenting practice. The
      implications for practice, service delivery and targeting at the individual level
      are noted.

PMID- 17212638
TI  - In vitro replication models for the hepatitis C virus.
AB  - Soon after the discovery of the hepatitis C virus (HCV), attention turned to the
      development of models whereby replication of the virus could be investigated.
      Among the HCV replication models developed, the HCV RNA replicon model and the
      newly discovered infectious cell culture systems have had an immediate impact on
      the study of HCV replication, and will continue to lead to important advances in
      our understanding of HCV replication. The aim of this study is to deal with
      developments in HCV replication models in a chronological order from the early
      1990s to the recent infectious HCV cell culture systems.

PMID- 17212639
TI  - Risk factors for hepatitis C fibrosis: a prospective study of United States
      veterans compared with nonveterans.
AB  - Chronic hepatitis C virus (HCV) infection causes cirrhosis in many infected
      patients; however, a better understanding of the risk factors for fibrosis
      progression in high HCV prevalence groups such as US veterans is needed. We
      wished to compare the demographic, clinical characteristics, and independent
      variables that influence fibrosis in US veterans vs nonveterans with chronic HCV.
      HCV-seropositive US veterans (n = 459) and nonveterans (n = 395) prospectively
      completed a detailed medical, social and occupational questionnaire. Clinical
      factors for progressive liver disease were compared between veterans and
      nonveterans and fibrosis stage assessed on liver biopsies (168 veterans and 208
      nonveterans). Using polychotomous logistic regression, fibrosis was analysed as
      both a progressive and categorical outcome to determine independent risk factors
      for both patient groups. Although veterans were significantly older and had
      higher lifetime alcohol consumption than nonveterans, their median fibrosis
      scores did not differ from nonveterans. By univariate analysis, alanine
      aminotransferase, necroinflammatory activity (NIA), and cryoglobulin positivity
      were associated with fibrosis in veterans and nonveterans (P < 0.05, all
      comparisons), whereas steatosis was associated with fibrosis only in nonveterans
      (P < 0.0001). By multivariate analysis, NIA was an independent risk factor for
      fibrosis in both groups (P < 0.01). However, fibrosis in nonveterans was also
      independently associated with steatosis, significant alcohol consumption and age
      (P < 0.04, all comparisons). Independent risk factors for fibrosis vary among
      high HCV prevalence groups such as veterans when compared with nonveterans.
      Understanding specific patient cohort effects is important for determining
      independent risk factors for disease progression in chronic HCV infection.

PMID- 17212640
TI  - Modifications of plasma platelet-activating factor (PAF)-acetylhydrolase/PAF
      system activity in patients with chronic hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) chronically infects about 200 million individuals
      worldwide and leads to severe liver and lymphatic diseases. HCV circulates in the
      serum, associated with apoB-containing lipoproteins. Platelet-activating factor
      (PAF), a pro-inflammatory mediator, is mainly modulated by plasma PAF
      acetylhydrolase (pPAF-AH), associated with ApoB100-containing low-density
      lipoproteins (LDL). The aim of the study was to evaluate the potential effects of
      chronic HCV infection on the PAF/pPAF-AH system. HCV-RNA was detected in plasma,
      peripheral blood mononuclear cells (PBMC) and liver samples. Plasma PAF levels,
      pPAF-AH activity, ApoB100 serum titres and pPAF-AH mRNA levels in cultured
      macrophages were determined. Plasma PAF levels were significantly higher and pPAF
      AH activity was significantly lower in HCV patients than in controls. No
      significant modifications of pPAF-AH mRNA in macrophages or in ApoB100 values
      were observed in HCV patients compared with controls. Patients who cleared HCV
      after antiviral treatment showed a complete restoration of pPAF-AH activity and
      significant decrease of PAF levels during the follow-up. No data exist about the
      PAF/pPAF-AH system behaviour during HCV infection. This study shows that in HCV
      patients modifications of pPAF-AH activity/PAF levels take place and that HCV
      clearance restored pPAF-AH activity. This suggests that circulating viral
      particles play a role in PAF/pPAF-AH system modifications and such an alteration
      could be involved in HCV-related damage.

PMID- 17212641
TI  - Impact of hepatic steatosis on viral kinetics and treatment outcome during
      antiviral treatment of chronic HCV infection.
AB  - Liver steatosis is highly prevalent in chronic hepatitis C virus (HCV) infection,
      especially in patients infected with genotype 3 virus, but its significance for
      the outcome of antiviral treatment is not fully understood. We have monitored
      steatosis in liver biopsies from 231 patients with chronic HCV infection who
      received pegylated recombinant interferon-alpha and ribavirin in a phase III
      study (DITTO trial). The degree of steatosis, along with relevant metabolic
      parameters, was correlated with the early disappearance of virus and with the
      final outcome of treatment. Our data suggest that the presence of steatosis
      impairs the early reduction of viral load during treatment in patients infected
      with HCV genotype 3 and non-3. Steatosis negatively affected the final outcome of
      treatment mainly in patients infected with HCV genotype non-3 virus. Based on
      these findings, we propose that interventions aiming at reducing hepatic
      steatosis prior to the onset of antiviral therapy may be of benefit to patients
      infected with HCV of the non-3 genotypes. Patients infected with genotype 3, on
      the other hand, should be offered early antiviral treatment.

PMID- 17212642
TI  - Comparative study between occult hepatitis C virus infection and chronic
      hepatitis C.
AB  - We have recently described the presence of occult hepatitis C virus (HCV)
      infection (HCV-RNA in liver in the absence of anti-HCV and serum HCV-RNA) in
      patients with persistently abnormal liver function tests of unknown aetiology.
      The aim of this study was to compare the characteristics of patients with occult
      HCV infection vs those of patients with chronic hepatitis C. We compared clinical
      features of 68 patients with occult HCV infection and 69 untreated chronic HCV
      patients (anti-HCV and serum HCV-RNA positive), matched for age, gender, duration
      of abnormal liver function tests and body mass index. Aspartate aminotransferase
      and alanine aminotransferase were higher (P < 0.001) in chronic HCV, but
      cholesterol and triglycerides were significantly higher in patients with occult
      HCV infection (P < 0.001 and P = 0.002). Chronic HCV patients had higher gamma
      globulin (P = 0.005), alpha-foetoprotein (P < 0.001) and iron (P < 0.001) levels.
      Percentage of patients with necroinflammatory activity and fibrosis was higher (P
      < 0.001) in chronic HCV than in occult HCV infection. Mean percentage of infected
      hepatocytes was higher (P = 0.001) in chronic HCV (10.1%) than in occult HCV
      infection (5.3%). This occult HCV infection is a milder disease than chronic HCV,
      and this could be related to the significantly lower number of infected
      hepatocytes observed in occult HCV.

PMID- 17212643
TI  - Real-time quantification of human telomerase reverse transcriptase mRNA in liver
      tissues from patients with hepatocellular cancer and chronic viral hepatitis.
AB  - We determined, for the first time, the human telomerase reverse transcriptase
      (hTERT) mRNA expression, using real-time quantitative PCR, in liver tissues from
      patients with hepatocellular cancer (HCC; n = 13), chronic hepatitis B (n = 19)
      and C (n = 13). Liver tissues from the 45 patients and 17 patients without liver
      disease in whom liver biopsy was performed during cholecystectomy (control
      group), were investigated for telomerase activity (TA) and hTERT mRNA expression
      using the LightCycler technology. TA was detected in all HCC tissues compared
      with 15.6% of chronic hepatitis (P < 0.001) and none of controls (P < 0.001). TA
      levels and hTERT mRNA were higher in HCC compared with chronic hepatitis (P <
      0.001) and normal livers (P < 0.001). hTERT mRNA expression was correlated with
      TA (P < 0.05). Chronic hepatitis patients who tested negative for TA and hTERT
      mRNA had significantly lower disease duration (58 +/- 85 months) compared with
      those tested positive (144 +/- 50 months; P < 0.05). Detection of TA and
      quantification of hTERT mRNA expression in liver tissues could be useful and
      additional markers for HCC diagnosis and may serve as prognostic markers for HCC
      development in chronic viral hepatitis patients. However, we were not able to
      draw general conclusions at this moment, as the number of chronic hepatitis
      patients positive for hTERT mRNA was relatively small. Real-time quantification
      of hTERT mRNA expression as a diagnostic/prognostic marker in patients with
      chronic hepatitis B and C and its relationship with hepatocarcinogenesis needs
      further evaluation.

PMID- 17212644
TI  - Anti-Helicobacter pylori seropositivity: influence on severity and treatment
      response in patients with chronic hepatitis C.
AB  - We sought to clarify the incidence and role of Helicobacter pylori (H. pylori)
      seropositivity in patients with hepatitis C virus (HCV) infection and the effect
      of coinfection on interferon-alpha and ribavirin therapy. The presence of H.
      pylori was tested using a commercially available enzyme immunoassay in serum
      samples from 93 patients with chronic hepatitis C. Clinical features, HCV markers
      and response of HCV to interferon-alpha and ribavirin were compared between H.
      pylori-positive and H. pylori-negative patients. Anti-H. pylori antibody was
      detected in 45 (48%) of the 93 patients, whose median HCV-RNA level (495 vs 760
      kIU/mL; P = 0.013) and platelet count (128 vs 158 x 10(3)/microL; P = 0.009) were
      significantly lower than in patients with HCV infection alone. Anti-H. pylori
      antibody levels were found to be significantly correlated with fibrosis score (P
      = 0.0083, r = 0.33) but inversely related to platelet count (P = 0.0037, r = 
      0.34). The sustained response rate for HCV clearance following interferon-alpha
      and ribavirin treatment did not differ between patients with and without anti-H.
      pylori seropositivity. The presence of H. pylori [odds ratio (OR) 8.61; 95%
      confidence interval (CI) 1.59-46.70] and fibrosis score (OR 30.13; 95% CI 5.44
      166.78) were found by multivariate analysis to be associated with the decrease of
      platelet count during therapy. Coexistent H. pylori infection does not
      demonstrably influence the clinical course of chronic hepatitis C. A possible
      connection between H. pylori coinfection and thrombocytopenia was found during
      the treatment course, suggesting that preemptive eradication of H. pylori may
      facilitate completion of treatment and increased sustained virological response.

PMID- 17212645
TI  - Quantitative analysis of HBV cccDNA from clinical specimens: correlation with
      clinical and virological response during antiviral therapy.
AB  - Attempts to investigate changes in various forms of intrahepatic hepatitis B
      virus (HBV) DNA during antiviral therapy have been hampered by limitations in
      technologies and scarcity of adequate tissue for analysis. We used a sensitive,
      specific assay to detect and quantitate covalently closed circular DNA (cccDNA)
      from total intrahepatic HBV DNA in clinical liver specimens. Total HBV DNA and
      cccDNA from 21 needle-biopsy specimens were quantified, with levels ranging from
      0.1 to 9.8 copies/cell and 0.3 to 491.0 copies/cell, respectively. Then, we
      performed the same determinations on baseline and week-52 liver needle-biopsy
      specimens from eight patients enrolled in a clinical trial and evaluated the
      association between intrahepatic HBV DNA levels and serological and virological
      endpoints. In most patients, levels of intrahepatic HBV DNA, including cccDNA,
      decreased over the 52-week study, regardless of therapy or serological outcome.
      Higher ratios of cccDNA to total HBV DNA were detected at week 52 than at
      baseline indicating a shift in predominance of nonreplicating virus in
      posttreatment specimens. In patients who achieved treatment-related or
      spontaneous hepatitis B e antigen (HBeAg) responses, including those harbouring
      tyrosine-methionine-aspartate-aspartate-mutant HBV, levels of intrahepatic and
      serum HBV DNA suppression were greater than those in patients without HBeAg
      responses. In conclusion, this pilot study of intrahepatic HBV replicative forms
      in patients with chronic hepatitis B indicated that total intrahepatic and,
      specifically, cccDNA levels are not static but change as a reflection of
      serological and virological events.

PMID- 17212646
TI  - Clinicopathological differences between hepatitis B viral genotype B- and C
      related resectable hepatocellular carcinoma.
AB  - Clinical and pathogenic differences exist between hepatitis B viral (HBV)
      genotypes B and C, and genotype C has a higher risk of hepatocellular carcinoma
      (HCC) development than genotype B. The aim of this study was to investigate
      whether HBV genotypes B and C influence the clinicopathological features of
      patients with resectable HCC. Stored serum samples from 193 patients with
      resectable HBV-related HCC were tested for HBV genotypes by a molecular method.
      Of 193 patients undergoing resection of HCC, 107 (55%) and 86 (45%) were infected
      with genotypes B and C, respectively. Compared with genotype C patients, genotype
      B patients were less likely to be associated with liver cirrhosis (33%vs 51%, P =
      0.01). Pathologically, genotype B patients had a higher rate of solitary tumour
      (94%vs 86%, P = 0.048) and more satellite nodules (22%vs 12%, P = 0.05) than
      genotype C patients. Our results indicate that genotype B-related HCC is less
      associated with liver cirrhosis and has a higher frequency of solitary tumour as
      well as more satellite nodules than genotype C-related HCC. These characteristics
      may contribute to the recurrence patterns and prognosis of HBV-related HCC in
      patients with genotype B or C infection.

PMID- 17212647
TI  - Nuclear HBcAg and histology activity index as independent predictors of the
      expression of singly spliced HBV-RNA.
AB  - Although hepatitis B virus (HBV) RNA splicing has been reported by many
      researchers, the clinical significance of this event remains illusive. The
      present study was designed to investigate the clinical roles of singly spliced
      HBV-RNA. Liver biopsy tissues obtained from 32 consecutive patients were
      subjected to reverse transcriptase-polymerase chain reaction for the detection of
      singly spliced and unspliced HBV-RNA. Stepwise linear regression model was used
      to estimate the ratio of singly spliced to unspliced (S/US) HBV-RNA in the
      presence of the following variables: age, gender, aspartate aminotransferase,
      alanine aminotransferase, total bilirubin, alpha-foetoprotein, status of HBV e
      antigen (HBeAg), status of antibody to HBeAg, HBV-DNA, histology activity index
      (HAI), fibrotic score, grade of cytoplasmic HBV core antigen (HBcAg), grade of
      nuclear HBcAg, genotype, status of precore-stop-mutation, basal core promoter
      mutation, previous lamivudine therapy and superinfection by other hepatitis
      viruses. The results showed that HAI (beta = -0.2616; P = 0.011) and grade of
      nuclear HBcAg expression (beta = 0.5599; P =0.0067) were two independent
      predictors for the expression of singly spliced HBV-RNA. Further categorical
      analysis showed that patients with HAI score <or=6 and grading of nuclear HBcAg
      >or=2 have significantly higher S/US ratios. In conclusion, nuclear HBcAg and HAI
      are two independent predictors for the expression of singly spliced HBV-RNA.

PMID- 17212649
TI  - C57BL/6J and DBA/2J mice vary in lick rate and ingestive microstructure.
AB  - Fluid licking in mice is an example of a rhythmic behavior thought to be under
      the control of a central pattern generator. Inbred strains of mice have been
      shown to differ in mean or modal interlick interval (ILI) duration, suggesting a
      genetic-based variation. We investigated water licking in the commonly used
      inbred strains C57BL/6J (B6) and DBA/2J (D2), using a commercially available
      contact lickometer. Results from 20-min test sessions indicated that D2 mice lick
      at a faster rate than B6 mice (10.6 licks/s vs. 8.5 licks/s), based on analysis
      of the distribution of short-duration ILIs (50-160 ms). This strain difference
      was independent of sex, extent of water deprivation or total number of licks. D2
      mice also displayed a faster lick rate when the strains were tested with a series
      of brief (5 s) trials. However, when ingestion over the entire 20-min session was
      analyzed, it was evident that D2 mice had an overall slower rate of ingestion
      than B6 mice. This was because of the tendency for D2 mice to have more very long
      pauses (>30 s) between sequences of licking bursts. Overall, it appeared that D2
      mice licked more efficiently, ingesting more rapidly during excursions to the
      spout that were fewer and farther between.

PMID- 17212648
TI  - Social reward among juvenile mice.
AB  - Mammalian social relationships, such as mother-offspring attachments and pair
      bonds, can directly affect reproductive output. However, conspecifics approach
      one another in a comparatively broad range of contexts, so conceivably there are
      motivations for social congregation other than those underlying reproduction,
      parental care or territoriality. Here, we show that reward mediated by social
      contact is a fundamental aspect of juvenile mouse sociality. Employing a novel
      social conditioned place preference (SCPP) procedure, we demonstrate that social
      proximity is rewarding for juvenile mice from three inbred strains (A/J, C57BL/6J
      and DBA/2J), while mice from a fourth strain (BALB/cJ) are much less responsive
      to social contact. Importantly, this strain-dependent difference was not related
      to phenotypic variability in exploratory behavior or contextual learning nor
      influenced by the genetic background associated with maternal care or social
      conditioning. Furthermore, the SCPP phenotype was expressed early in development
      (postnatal day 25) and did not require a specific sex composition within the
      conditioning group. Finally, SCPP responses resulted from an interaction between
      two specifiable processes: one component of the interaction facilitated approach
      toward environments that were associated with social salience, whereas a second
      component mediated avoidance of environmental cues that predicted social
      isolation. We have thus identified a genetically prescribed process that can
      attribute value onto conditions predicting a general form of social contact. To
      our knowledge, this is the first definitive evidence to show that genetic
      variation can influence a form of social valuation not directly related to a
      reproductive behavior.

PMID- 17212651
TI  - Genome-wide and locus-specific DNA hypomethylation in G9a deficient mouse
      embryonic stem cells.
AB  - In the mammalian genome, numerous CpG-rich loci define tissue-dependent and
      differentially methylated regions (T-DMRs). Euchromatin from different cell types
      differs in terms of its tissue-specific DNA methylation profile as defined by
      these T-DMRs. G9a is a euchromatin-localized histone methyltransferase (HMT) and
      catalyzes methylation of histone H3 at lysines 9 and 27 (H3-K9 and -K27). To test
      whether HMT activity influences euchromatic cytosine methylation, we analyzed the
      DNA methylation status of approximately 2000 CpG-rich loci, which are predicted
      in silico, in G9a(-/-) embryonic stem cells by restriction landmark genomic
      scanning (RLGS). While the RLGS profile of wild-type cells contained about 1300
      spots, 32 new spots indicating DNA demethylation were seen in the profile of G9a(
      /-) cells. Virtual-image RLGS (Vi-RLGS) allowed us to identify the genomic source
      of ten of these spots. These were confirmed to be cytosine demethylated, not just
      at the Not I site detected by the RLGS but extending over several kilobase pairs
      in cis. Chromatin immunoprecipitation (ChIP) confirmed these loci to be targets
      of G9a, with decreased H3-K9 and/or -K27 dimethylation in the G9a(-/-) cells.
      These data indicate that G9a site-selectively contributes to DNA methylation.

PMID- 17212650
TI  - The Trace Amine 1 receptor knockout mouse: an animal model with relevance to
      schizophrenia.
AB  - Trace amines have been implicated in a number of neuropsychiatric disorders
      including depression and schizophrenia. Although long known to modulate
      neurotransmission indirectly through the release of catecholamines, the
      identification of the Trace Amine 1 receptor (TA1) offers a mechanism by which
      trace amines can influence synaptic activity directly. TA1 binds and is activated
      by trace amines such as beta-phenylethylamine and tyramine. Our pharmacological
      characterization of mouse TA1 showed that, as in rat and primate, amphetamine is
      an agonist at this receptor but with surprisingly high potency. Without selective
      ligands for TA1 that do not also possess catecholamine-releasing properties,
      however, it has not been possible to study its physiological role in the central
      nervous system. To that end, a line of mice lacking the TA1 receptor was
      generated to characterize its contribution to the regulation of behavior.
      Compared with wild-type littermates, TA1 knockout (KO) mice displayed a deficit
      in prepulse inhibition. Knockout animals, in which the TA1-agonist influence of
      amphetamine was absent, showed enhanced sensitivity to the psychomotor
      stimulating effect of this drug, which was temporally correlated with
      significantly larger increases in the release of both dopamine and norepinephrine
      in the dorsal striatum and associated with a 262% increase in the proportion of
      striatal high-affinity D2 receptors. TA1 therefore appears to play a modulatory
      role in catecholaminergic function and represents a potentially novel mechanism
      for the treatment of neuropsychiatric disorders. Furthermore, the TA1 KO mouse
      may provide a useful model for the development of treatments for some positive
      symptoms of schizophrenia.

PMID- 17212653
TI  - Participation of XPB/Ptr8p, a component of TFIIH, in nucleocytoplasmic transport
      of mRNA in fission yeast.
AB  - To identify novel factors involved in nuclear mRNA export in Schizosaccharomyces
      pombe, we isolated and characterized the ptr8(+) gene, mutation of which causes
      nuclear accumulation of poly (A)(+) RNA. The ptr8(+) gene encodes an S. pombe
      homologue of human XPB, a component of TFIIH involved in nucleotide excision
      repair (NER) and transcription. A temperature-sensitive mutant of ptr8(+) (ptr8
      1) was highly sensitive to UV irradiation, as are human XPB cells. Northern blot
      analysis demonstrated that the amount of total poly (A)(+) mRNAs does not
      decrease significantly at the nonpermissive temperature in ptr8-1 cells, whereas
      a pulse-labeling assay using (35)S-methionine showed that protein synthesis
      decreases rapidly after incubation of cells at the nonpermissive temperature,
      suggesting that ptr8-1 cells have a defect in nuclear mRNA export. In
      Saccharomyces cerevisiae, a mutation in the SSL2 gene encoding a homologue of
      Ptr8p also causes a block of mRNA export at the nonpermissive temperature. In
      addition, expression of human XPB in ptr8-1 cells rescued the ts phenotype and
      the mRNA export defects, suggesting that human XPB may also play a role in mRNA
      export. Furthermore, we revealed a functional interaction between Ptr8p and
      Tho2p, a component of the TREX complex involved in mRNA export. These results
      suggest that XPB/Ptr8p plays roles not only in NER and transcription, but also
      plays a conserved role in mRNA export.

PMID- 17212652
TI  - Global analysis of functional surfaces of core histones with comprehensive point
      mutants.
AB  - The core histones are essential components of the nucleosome that act as global
      negative regulators of DNA-mediated reactions including transcription, DNA
      replication and DNA repair. Modified residues in the N-terminal tails are well
      characterized in transcription, but not in DNA replication and DNA repair. In
      addition, roles of residues in the core globular domains are not yet well
      characterized in any DNA-mediated reactions. To comprehensively understand the
      functional surface(s) of a core histone, we constructed 320 yeast mutant strains,
      each of which has a point mutation in a core histone, and identified 42 residues
      responsible for the suppressor of Ty (Spt(-)) phenotypes, and 8, 30 and 61
      residues for sensitivities to 6-azauracil (6AU), hydroxyurea (HU) and methyl
      methanesulfonate (MMS), respectively. In addition to residues that affect one
      specific assay, residues involved in multiple reactions were found, and
      surprisingly, about half of them were clustered at either the nucleosome entry
      site, the surface required for nucleosome-nucleosome interactions in crystal
      packing or their surroundings. This comprehensive mutation approach was proved to
      be powerful for identification of the functional surfaces of a core histone in a
      variety of DNA-mediated reactions and could be an effective strategy for
      characterizing other evolutionarily conserved hub-like factors for which surface
      structural information is available.

PMID- 17212654
TI  - Dvl regulates endo- and exocytotic processes through binding to synaptotagmin.
AB  - Dvl, an important component of the Wnt signalling pathway, is thought to be
      involved in synaptogenesis. In this study, we investigated whether Dvl regulates
      neurotransmitter release. Knockdown of Dvl in PC12 cells suppressed K(+)-induced
      dopamine release, and this phenotype was restored by expression of Dvl-1. We
      identified synaptotagmin (Syt) I, which is involved in neurotransmitter release,
      as a Dvl-binding protein. Dvl directly bound to the C2B domain of Syt I. Dvl
      colocalized with Syt I at the tip of neurites of differentiated PC12 cells and of
      neurons in the rat dorsal root ganglion. Dvl and Syt I was located in large dense
      core vesicles, which contain dopamine. In addition, endocytosis of vesicles
      containing Syt I was suppressed in Dvl knockdown PC12 cells. Dvl inhibited the
      binding of Syt I to the complex consisting of syntaxin-1A and SNAP-25.
      Furthermore, micro2-adaptin of AP-2, which is known to play a role in
      endocytosis, formed a complex with Dvl and Syt I. Taken together, these results
      suggest that Dvl is involved in endo- and exocytotic processes through the
      binding to Syt I.

PMID- 17212656
TI  - Cys669-Cys713 disulfide bridge formation is a key to dystroglycan cleavage and
      subunit association.
AB  - Dystroglycan (DG) is a widely expressed, transmembrane glycoprotein complex that
      plays important roles by connecting the extracellular matrix to the cytoskeleton.
      The alpha- and beta-DG subunits are produced by the cleavage of residues 653 and
      654 of the precursor. To clarify the mechanisms involved in cleavage and subunit
      association, we performed a series of mutation analyses and made the following
      discoveries: (i) Disruption of the intramolecular disulfide bridge between Cys669
      and Cys713 in beta-DG completely abolishes the cleavage, (ii) deletions in the
      loop region (669-713) and in the C-terminal region of alpha-DG (550-645) abolish
      the cleavage, (iii) disruption of the disulfide bridge and deletions in the loop
      region deteriorate the alpha- and beta-DG subunit association, and (iv) at the
      cleavage site, especially, positions P1' (Ser654) and P6' (Trp659) are critical.
      Thus, the critical role of the Cys669-Cys713 disulfide bridge formation is, most
      likely, to form a specific tertiary structure, in which the alpha- and beta-DG
      domains interact and the cleavage site becomes susceptible to proteolytic
      reactions. The Cys669 and Cys713 pair is broadly conserved in vertebrates and in
      some invertebrates, suggesting that the disulfide bridge formation was
      established early in the evolution of DG.

PMID- 17212655
TI  - Extracellular domain splice variants of a transforming protein tyrosine
      phosphatase alpha mutant differentially activate Src-kinase dependent focus
      formation.
AB  - The extracellular domains of receptor-type protein-tyrosine phosphatases (PTPs)
      contain a diverse range of protein modules like fibronectin- or immunoglobulin
      like structures. These are frequently expressed in a tissue- and development
      specific manner as splice variants. The extracellular domain of PTPalpha is
      rather short and heavily glycosylated. Two splice variants are known, which it
      differs by an exon encoding nine amino acids within the extracellular domain. We
      have analyzed the expression pattern of both variants and found that the smaller
      form is ubiquitously expressed while the larger form was found at an increased
      level only in brain, some skeletal muscle and differentiating cells like granule
      neurons, adipocytes and myotubes. The phosphatase activity of both forms was
      similar when tested in vitro using para-nitrophenylphosphate as a substrate and
      in a transient expression system with the substrates c-Fyn or c-Src. In a
      quantitative focus formation assay the capability of the larger form to activate
      Src-dependent focus formation in intact cells was increased more than twofold
      whereas the capability to dephosphorylate the insulin receptor in a BHK cell
      system was similar. We conclude that the two splice variants of PTPalpha are
      expressed differentially and regulate c-Src activity in different ways.

PMID- 17212657
TI  - Polarized exocytosis and transcytosis of Notch during its apical localization in
      Drosophila epithelial cells.
AB  - Notch (N) and its ligands, Delta (Dl) and Serrate (Ser), are transmembrane
      proteins that mediate the cell-cell interactions necessary for many cell-fate
      decisions. In Drosophila, N is predominantly localized to the apical portion of
      epithelial cells, but the mechanisms and functions of this localization are
      unknown. Here, we found N, Dl, and Ser were mostly located in the region from the
      subapical complex (SAC) to the apical portion of the adherens junctions (AJs) in
      wing disc epithelium. N was delivered to the SAC/AJs in two phases. First,
      polarized exocytosis specifically delivered nascent N to the apical plasma
      membrane and AJs in an O-fut1-independent manner. Second, N at the plasma
      membrane was relocated to the SAC/AJs by Dynamin- and Rab5-dependent
      transcytosis; this step required the O-fut1 function. Disruption of the apical
      polarity by Drosophila E-cadherin (DEcad) knock down caused N and Dl localization
      to the SAC/AJs to fail. N, but not Dl, formed a specific complex with DEcad in
      vivo. Finally, our results suggest that juxtacrine signaling in epithelia
      generally depends on the apicobasally polarized structure of epithelial cells.

PMID- 17212658
TI  - Regulated nucleo-cytoplasmic shuttling of human aci-reductone dioxygenase (hADI1)
      and its potential role in mRNA processing.
AB  - Bacterial aci-reductone dioxygenase (ARD), a member of the cupin superfamily, has
      evolutionarily primitive protein folding and functions in the methionine
      recycling pathway. Recently, a human ARD orthologue (human ADI1, hADI1) has been
      identified and exhibits functions other than ARD activity. The hADI1 localizes
      mainly to the cytoplasm, but a substantial fraction is nuclear, suggesting
      functions in both cellular compartments. In this study, we report that nucleo
      cytoplasmic transport of hADI1 is regulated by a non-canonical nuclear export
      signal (NES) located in the N-terminal region of hADI1. The NES is composed of
      multiple basic amino-acid residues instead of the canonical leucine-rich
      sequence. Nuclear export of hADI1 was not mediated by CRM1, a major transporter
      that binds to leucine-rich NES. Substitution of the basic residues with alanines
      abolished NES activity. Mutant hADI1 accumulated in the nucleus and formed
      speckles frequently observed with splicing factors and some transcription
      factors. Indeed, hADI1 specifically co-localized with the splicing factor U1-70K
      to the nucleus but not with another splicing factor, SC35. U1-70K over-expression
      induced nuclear accumulation of hADI1. Nuclear hADI1 expression significantly
      altered the splicing pattern of the adenovirus E1A mini-gene, which generates
      multiple alternatively spliced transcripts. Thus, hADI1 may have acquired a novel
      role in nuclear mRNA processing possibly by modulating U1-70K-related functions,
      an activity negatively regulated by a non-classical NES sequence.

PMID- 17212659
TI  - A kinase subunit of the human mediator complex, CDK8, positively regulates
      transcriptional activation.
AB  - The human thyroid hormone receptor-associated proteins (TRAP)/Mediator and
      related complexes mediate transcription through regulatory factors. To further
      understand the structural and functional diversity of these complexes we
      established three HeLa cell lines each expressing one of three epitope-tagged
      human TRAP/Mediator subunits, MED6, MED7, and CDK8 and isolated the complexes in
      which these subunits were contained by affinity and HPLC-gel filtration
      chromatography. The largest complexes from each cell line had a molecular mass of
      1.5 MDa and possessed almost identical subunit compositions; we designated these
      complexes TRAP/Mediator-like complex 1 (TMLC1). Two potential subcomplexes were
      additionally observed: a 1-MDa complex from the CDK8-cell line (TMLC2) and a 600
      kDa complex from the MED6-cell line (TMLC3). All three complexes regulated
      transcription in vitro; TMLC1 and TMLC3 augmented transcriptional activation,
      whereas TMLC2 repressed it. TMLC1 and TMLC2 phosphorylated RNA polymerase II (Pol
      II), but TMLC3 did not. Furthermore, TMLC1 predominantly interacted with the
      general transcription factors TFIIE, TFIIF, and TFIIH, which function during
      transcription initiation and the transition to elongation. In a final experiment,
      knockdown of CDK8 using RNA interference prevented transcriptional activation by
      Gal4-VP16 in a luciferase-assay. This, together with the effect of TMLC1 on
      transcription in vitro, suggests that CDK8 play positive roles in transcriptional
      activation.

PMID- 17212660
TI  - Role of endocrine and growth factors on the ovarian surface epithelium.
AB  - Epithelial ovarian cancer is a highly fatal disease for which prevention
      strategies have been limited; in part because of our poor understanding of the
      underlying biology of its precursor, the ovarian surface epithelium (OSE). The
      OSE is a single layer of flat-to-cuboidal mesothelial cells that covers the
      surface of the ovary. Despite its inconspicuous appearance in vivo, it is
      believed that OSE cells actively participate in the cyclical ovulatory rupture
      and repair process. The continuous rupture of the OSE at ovulation and the
      subsequent proliferation to repair the wound renders the cells susceptible to
      genetic damage and malignant transformation. As the ovary is a rich source of
      multiple hormones, and normal OSE and ovarian carcinomas secrete and have
      receptors for hormones, growth factors and cytokines, these factors are strong
      candidates to regulate normal OSE physiology and the transformation and
      progression of ovarian cancers. In particular, alterations of hormone/growth
      factor production and receptor expression are common in ovarian tumors. This
      review summarizes the current knowledge in the field of endocrinology and its
      relationship to the biology and pathology of the OSE.

PMID- 17212661
TI  - Effect of HER-2/neu overexpression on chemoresistance and prognosis in ovarian
      carcinoma.
AB  - AIM: To investigate the effect of HER-2/neu protein overexpression on
      chemoresistance and prognosis in patients with epithelial ovarian carcinoma.
      METHODS: A total of 141 ovarian carcinoma tissues surgically resected between
      1987 and 2003 were assessed by immunohistochemistry (IHC). The characteristic of
      the patients and immunohistochemical results were compared by chi2-test. Survival
      analysis was performed by the Kaplan-Meier method and the log-rank test. RESULTS:
      HER-2/neu overexpression was detected in 18 cases (12.8%). There were no
      significant differences in histopathological subtypes (P = 0.3550), FIGO stages
      (P = 0.8858), or residual tumor size at first surgery (P = 0.6607) between the
      cases with HER-2/neu overexpression and the cases without HER-2/neu
      overexpression. Among the 58 cases which responded to chemotherapy, only five
      cases (8.6%) showed HER-2/neu overexpression. However, among the 38 cases which
      did not respond to chemotherapy, eight cases (21.1%) showed HER-2/neu
      overexpression. Overexpression of HER-2/neu had a tendency to relate with
      chemoresistance of epithelial ovarian carcinoma, but there were no statistically
      significant differences (P = 0.0817). No association was observed between HER
      2/neu overexpression and cumulative survival rate (P = 0.4970). CONCLUSIONS: The
      results of the current study show that although HER-2/neu overexpression has a
      tendency to be associated with chemoresistance, it can not be a prognostic factor
      for the patients with epithelial ovarian carcinoma.

PMID- 17212662
TI  - Allogeneic and autologous ovarian orthotopic transplantation without a vascular
      pedicle: morphological, endocrinologic and natural pregnancy assessment.
AB  - BACKGROUND: To assess the natural pregnancy of rabbits submitted to bilateral
      oophorectomy and orthotopic allogeneic or autologous intact and sliced ovarian
      transplantation without a vascular pedicle, and to determine the morpho
      functional aspects of the transplanted ovaries. METHODS: Fifty-six female rabbits
      were studied. The ovaries were removed and orthotopically transplanted or
      replaced without vascular anastomoses: Group 1 (n = 8), only laparotomy and
      laparorrhaphy; Group 2A (n = 8), intact ovaries were transplanted on both sides;
      Group 2B (n = 8), both ovaries were sliced and orthotopically transplanted; Group
      2C (n = 8), an intact ovary was transplanted on one side and a sliced ovary on
      the other side; Groups 3A-C, the ovaries were reimplanted according to the
      procedure and subgroups described for Group 2. Three months later, the animals
      were paired with males for copulation. Estradiol, progesterone, FSH and LH
      hormone levels were assessed. A histological study was carried out, and the
      number of pregnancies and litters were also determined. Chi-squared test compared
      the number of pregnancies and litters. One-way anova and the Tukey-Kramer tests
      compared the hormonal dosages. RESULTS: Pregnancies occurred in seven rabbits of
      Group 1, in 37.5% of rabbits in Groups 2A and 3A, in 50% of groups 2B, 3B and 3C,
      and in 62.5% of group 2C. Hormone levels and histology confirmed the vitality of
      all ovaries. CONCLUSIONS: Intact or sliced orthotopic allogeneic and autologous
      ovarian transplantation without a vascular pedicle is viable in rabbits, and
      preserves their hormonal and fertile functions.

PMID- 17212663
TI  - Association of microsomal epoxide hydrolase gene polymorphism and pre-eclampsia
      in Turkish women.
AB  - AIM: To assess the association between human epoxide hydrolase exon 3 and 4
      polymorphisms and pre-eclampsia by carrying out a case-control study in Turkish
      women. METHODS: DNA was extracted from peripheral blood leukocytes, and genotype
      distribution of exon 3 and exon 4 of epoxide hydrolase gene (EPHX) was carried
      out in 271 patients and 155 controls. RESULTS: There was no statistically
      significant difference in the distribution of genotypes between pre-eclampsia
      without HELLP and pre-eclampsia plus HELLP cases and controls for the exon 3 and
      4 polymorphism of EPHX. However, we found a significant association between the
      predicted enzyme activity level and pre-eclampsia (P = 0.018). The distribution
      of subjects with predicted high, intermediate and low microsomal epoxide
      hydrolase enzyme (EPHX) activity were 23.2, 38.8 and 38% in cases and 12, 47.3
      and 40.7% in controls, respectively. CONCLUSION: Although we could not find any
      association between genetic variability in exon 3 and 4 of EPHX and pre
      eclampsia, genetic variability in these two exons jointly modifies the predicted
      enzyme activity and may be a risk factor for pre-eclampsia.

PMID- 17212664
TI  - Interleukin-8 and glucose in amniotic fluid, fetal fibronectin in vaginal
      secretions and preterm labor index based on clinical variables are optimal
      predictive markers for preterm delivery in patients with intact membranes.
AB  - AIM: Various predictive markers for preterm delivery have been proposed in
      previous studies. We investigated which marker is most reliable. METHODS: In 126
      patients with preterm labor before 32 weeks of gestation and intact membranes,
      who had regular uterine contractions with cervical changes effaced > or =50%, we
      evaluated seven markers: interleukin (IL)-8, glucose, and granulocyte count in
      amniotic fluid (AF); fetal fibronectin (fFN) in vaginal secretions; IL-8 in
      cervical mucus; cervical length; and preterm labor index (PLI) based on clinical
      variables. The relationships of these variables to the occurrence of preterm
      delivery before 34 weeks were examined by logistic regression analysis. RESULTS:
      Values for AF IL-8, AF granulocyte count, fFN in vaginal secretions, and PLI were
      significantly higher, while the value for AF glucose was significantly lower, in
      patients delivering before 34 weeks than those in patients delivering at or
      following 34 weeks (P < 0.0001 for all). The most sensitive marker for predicting
      delivery before 34 weeks was AF IL-8 (sensitivity, 67.8%). The most specific
      markers were AF IL-8 (specificity, 95.5%) and PLI (specificity, 95.5%). By the
      logistic regression analysis, AF IL-8, AF glucose, fFN in vaginal secretions and
      PLI showed independent relationships with delivery before 34 weeks (P = 0.0009, P
      = 0.0032, P = 0.0131 and P = 0.0038, respectively). CONCLUSIONS: In preterm labor
      with intact membranes, AF IL-8, AF glucose, fFN in vaginal secretions and PLI
      were highly predictive markers for detecting preterm delivery before 34 weeks.

PMID- 17212665
TI  - Regional population-based study on pregnancy outcomes in women with diabetes
      mellitus in Japan.
AB  - AIM: We compared pregnancy outcomes in diabetic women with the background
      population in Miyazaki, Japan. METHODS: In 1998, we started the regional,
      population-based, peer-review conference to investigate the possible causes of
      perinatal deaths. For this purpose, at least one obstetrician and one
      neonatologist congregated from each institution (one tertiary and five secondary
      perinatal centers). A retrospective, population-based study was conducted in a
      total of 53 862 deliveries during 1999-2003. Among them, there were 248 perinatal
      deaths including six deaths in association with diabetes mellitus (DM). The
      number of diabetic pregnancies was estimated to be 381 during the study period.
      Perinatal mortality was compared between the diabetic women and background
      population by chi2-test. RESULTS: The perinatal mortality rate in diabetic women
      was 15.7 per 1000 deliveries, which was compared with 4.6 per 1000 in the
      background population (P = 0.003; odds ratio: 3.5; 95% confidence interval: 1.5
      7.9). Four of the six perinatal deaths in diabetes were sudden intrauterine
      demises after 37 weeks' gestation, and the others were neonatal deaths of
      congenital heart anomaly or extreme prematurity. Most deaths were attributable to
      either undiagnosed or insufficient perinatal management. CONCLUSIONS: In an
      unselected population in Japan, diabetic women have 3.5 times the reported risk
      of perinatal mortality of the general population. Further improvements in the
      diagnosis and management of DM during pregnancy are required.

PMID- 17212666
TI  - Outcomes of multifetal pregnancies.
AB  - AIM: To determine the outcomes of multifetal pregnancies and to compare maternal
      and neonatal complications between spontaneously conceived and assisted
      reproductive therapy. METHODS: A retrospective analysis was conducted of the
      information from medical records relating to all multifetal pregnancies. The
      outcomes were analyzed and used for a comparison between spontaneous and assisted
      multifetal pregnancies. RESULTS: There were 387 multifetal pregnancies during the
      study period, which was 1.3% of all the deliveries; 334 cases (86.3%) were
      spontaneous conceptions and 53 cases (13.7%) were the result of assisted
      reproductive therapy. Higher-order fetuses (> or =3) represented 8% of all
      multifetal pregnancies, 13% in the spontaneous group and 87% in the assisted
      group. The overall cesarean delivery rate was 73.9%. The assisted reproductive
      therapy group had a cesarean rate of 90.6% compared with 71.3% in the spontaneous
      group (P = 0.008). The assisted multifetal pregnancy group had more preterm
      labors and a longer maternal hospital stay than the spontaneous group. One
      maternal death occurred in the assisted group. The main causes of early neonatal
      death were prematurity, infection and congenital malformation. The newborns in
      the assisted group had more complications than the spontaneous group; most
      notable were respiratory distress syndrome, newborn intensive care admission,
      infection and longer hospital stay (6 days vs 15 days, P < 0.001). More
      complications occurred in higher-order fetuses than with twins. CONCLUSIONS:
      Assisted multifetal pregnancies were more likely to be delivered by cesarean
      section and had a higher rate of higher-order fetuses, preterm birth and neonatal
      prematurity-related complications with a longer hospital stay in both mothers and
      newborns, than spontaneous multifetal pregnancies.

PMID- 17212668
TI  - Folic acid prevents neural tube defects: international comparison of awareness
      among obstetricians/gynecologists and urologists.
AB  - AIM: It has been suggested that periconceptional intake of folic acid prevents
      risks of having fetuses afflicted with neural tube defects. We aim to
      internationally investigate knowledge of the role of folic acid and attitudes
      toward the life-style of young women of child-bearing age among
      obstetricians/gynecologists and urologists. METHODS: A questionnaire was sent to
      obstetricians/gynecologists and urologists residing in Japan, South Korea,
      Taiwan, North America, Europe, Australia and New Zealand by post or e-mail. The
      investigation was conducted between December 2002 and November 2004. RESULTS: A
      mean of 91% of obstetricians/gynecologists and 56% of urologists are aware of the
      role of folic acid, where Asian urologists knew less compared to those of North
      America, Europe, Australia and New Zealand. A majority of doctors always, or
      occasionally, recommend folic acid supplements or multivitamins, well-balanced
      meals, and the cessation of smoking and drinking. An average of 85% of doctors
      believes information on folic acid should be disseminated to young women.
      CONCLUSIONS: A majority of obstetricians/gynecologists and urologists know the
      importance of periconceptional folic acid in reducing the risk of neural tube
      defects and have been advising young women to improve their lifestyle.

PMID- 17212667
TI  - Morbidity and mortality associated with pre-eclampsia at two tertiary care
      hospitals in Sri Lanka.
AB  - AIM: To report the occurrence of morbidity and mortality associated with
      carefully phenotyped pre-eclampsia in a sample of nulliparous Sinhalese women
      with strictly defined disease. METHODS: A phenotyping database of 180 nulliparous
      women with pre-eclampsia and 180 nulliparous normotensive pregnant women who were
      recruited for a study into genetics of pre-eclampsia was analyzed. RESULTS: Women
      who developed pre-eclampsia had significantly higher systolic blood pressure
      (SBP; P = 0.002) and diastolic blood pressure (DBP; P = 0.002) at booking (at
      approximately 13 weeks of gestation). 38.3%, 28.3% and 33.3% of women delivered
      at <34 weeks, at 34-36 weeks, and at term, respectively. 78% required a cesarean
      section. Complications included SBP > or = 160 mmHg (75.5%); DBP > or = 110 mmHg
      (83.8%); proteinuria > or =3 + (150 mg/dL) in the urine protein heat coagulation
      test (87%); renal failure requiring dialysis (2%); platelet counts <100 x 10(9)/L
      (13%); > or =70 U/L in aspartate and/or alanine aminotransaminase (15%);
      placental abruption (4%); eclampsia (9%); and one maternal death. Maternal
      complications indicative of severe disease, apart from the incidence of SBP > or
      = 160 mmHg and DBP > or = 110 mmHg, were not significantly different in early and
      late-onset pre-eclampsia; fetal outcome was better with late-onset disease. 48%
      of babies were small for gestational age. Only 80 of 135 babies of women with pre
      eclampsia whose condition could be confirmed at 6 weeks post-partum were alive.
      CONCLUSIONS: Pre-eclampsia in Sinhalese women is associated with severe maternal
      morbidity and fetal morbidity and mortality, suggesting that modification of the
      Western diagnostic criteria and/or guidelines for medical care may be necessary.
      There is an urgent need to improve neonatal intensive care services in Sri Lanka.

PMID- 17212670
TI  - Sonographic features of hemivertebra at 13 weeks' gestation.
AB  - Hemivertebra is a rare congenital spinal disorder where only one side of the
      vertebral body develops, leading to deformation of the spine, such as scoliosis
      or kyphosis. Previous reports suggest that the diagnosis may be based on
      antenatal sonographic examination after 14 weeks. We present the sonographic
      features of a fetus with solitary hemivertebra at 13 weeks' gestation confirmed
      by postmortem babygram, magnetic resonance imaging (MRI) and pathological
      examination. It shows that the condition may manifest in the first trimester of
      pregnancy.

PMID- 17212669
TI  - Tibolone therapy in breast cancer survivors: a retrospective study.
AB  - AIM: To investigate a possible relationship between tibolone therapy and
      recurrence or mortality in breast cancer survivors. METHODS: In a retrospective
      study, data from files of 247 patients who had been treated for breast cancer
      were analyzed. Twenty women were treated with tibolone because of menopausal
      symptoms (Group 1: mean duration of tibolone use 37.1 months). One hundred and
      one women who did not take tibolone were selected as the control group (Group 2).
      All women were followed up in our Department on our standard protocol (mean
      follow up: 73.4 months in Group 1, 67.4 months in Group 2). Comparison of the
      survival curves was applied with the Wilcoxon (Gehan) statistic. Cox regression
      analysis was also applied in order to identify significant coefficients in the
      survival curve. RESULTS: Recurrence of breast cancer was observed in two (10%)
      Group 1 women versus 21 (21%) Group 2 women (P = NS). Two Group 1 women died (one
      from breast cancer recurrence) versus 15 Group 2 women (14 from breast cancer
      recurrence). CONCLUSIONS: Despite of the inherent limitations of this small
      retrospective study, it seems that tibolone does not reveal an apparent negative
      impact on breast cancer outcome when given to breast cancer survivors.

PMID- 17212671
TI  - Cerebral venous thrombosis and hepatic venous thrombosis during pregnancy.
AB  - Cerebral venous thrombosis (CVT) and Budd-Chiari syndrome (BCS) are rarely
      encountered thrombotic diseases of two different vascular systems. A 20-year-old
      woman in the 14th week of pregnancy was brought to the emergency department with
      complaints of sudden headache and loss of vision. Thrombosis in the left
      transverse and sigmoid sinus was demonstrated at MR angiography. She was
      diagnosed with BCS by using hepatic Doppler ultrasonography after an elevation of
      liver enzymes. Although CVT and BCS are rarely seen during pregnancy, they need
      emergency treatment because of high mortality.

PMID- 17212672
TI  - Placental mesenchymal dysplasia.
AB  - Placental mesenchymal dysplasia is a very rare disorder in which the placenta is
      enlarged and contains cystic villi and dilated vasculature. The authors present a
      new case report of placental mesenchymal dysplasia with severe fetal growth
      restriction.

PMID- 17212673
TI  - Torsion of the normal ovary and oviduct in a pre-pubertal girl.
AB  - We encountered a 10-year-old prepubertal girl with a normal ovary and oviduct
      torsion. Hemorrhagic infarction of the ovary and oviduct occurred, and these
      structures were laparoscopically removed. Torsion of the normal ovary and oviduct
      in a prepubertal girl is discussed.

PMID- 17212674
TI  - Giant ovarian cancer weighing 100 kg with poor prognosis.
AB  - We encountered a patient with giant ovarian cancer with a tumor weight of 100 kg.
      The patient's girth measured 198 cm after approximately 4 years' duration, and
      she complained of dyspnea and inability to walk. Adnectomy was performed with
      intensive intraoperative monitoring. The ovarian cancer was entirely adherent to
      the parietal peritoneum. However, 10 h after adnectomy, she died of massive
      abdominal bleeding from extremely redundant parietal peritoneum caused by
      disseminated intravascular coagulation.

PMID- 17212675
TI  - Serous ovarian carcinoma recurring as a heterologous carcinosarcoma.
AB  - Only two cases of recurrence of heterologous carcinosarcoma from adenocarcinoma
      of the ovary have been documented in the published literature. We report a case
      of serous ovarian carcinoma recurring as a heterologous carcinosarcoma. The
      immunohistochemical analysis of several biological parameters in primary ovarian
      adenocarcinoma and recurrent carcinosarcoma has been also performed.

PMID- 17212676
TI  - Assessment of headache diagnosis. A comparative population study of a clinical
      interview with a diagnostic headache diary.
AB  - The level of agreement between headache information, attained by clinical
      interview and headache diary, was evaluated in subjects who frequently suffered
      from headache and were participating in an epidemiological study of headache. One
      hundred and six subjects were interviewed and asked to complete a diary for a
      period of 4-8 weeks; 46% completed the study. For migraine the diary and clinical
      diagnoses demonstrated agreement in 82%, kappa value 0.57, sensitivity 90% and
      specificity 64%. For tension-type headache they demonstrated agreement in 87%,
      kappa value 0.39, sensitivity 97%, specificity 29% and a good agreement of
      frequency of tension-type headache was also obtained. In migraine, but not in
      tension-type headache, accompanying symptoms tended to be overestimated in the
      interview. The diary was not useful for the diagnosis of migraine with aura, but
      proved valuable in distinguishing between migraine and tension-type headache, and
      in the identification of coexisting headache disorders. Combined use of a
      diagnostic diary and clinical interview is recommended.

PMID- 17212677
TI  - Haemochromatosis gene (HFE) polymorphisms and migraine: an association study.
AB  - Several studies have suggested that iron metabolism may be involved in the
      pathogenesis of migraine. Using a case-control design, we performed an
      association study in a cohort of Italian migraine patients to evaluate whether a
      particular allele or genotype of the haemochromatosis gene (HFE) would modify the
      occurrence and clinical features of the disease. We genotyped 256 migraine
      patients and 237 healthy age-, sex- and ethnicity-matched controls for the C282Y
      and H63D polymorphisms of the HFE gene. Phenotype and allele frequencies of both
      polymorphisms were similarly distributed in migraine patients and controls. The
      patients carrying the DD genotype of the H63D polymorphism showed a later age at
      onset of the disease and an increased number of migraine attacks. Our data
      suggest that the HFE gene is not a major disease gene for migraine. However, the
      H63D polymorphism of the HFE gene may be considered a modifying genetic factor in
      migraine.

PMID- 17212678
TI  - Adolescent disc degeneration--no headache association.
AB  - The objective of the study was to determine whether adolescents with headache
      have more disc degeneration in the cervical spine than headache-free controls.
      This study is part of a population-based follow-up study of adolescents with and
      without headache. At the age of 17 years, adolescents with headache at least
      three times a month (N = 47) and adolescents with no headache (N = 22)
      participated in a magnetic resonance imaging (MRI) study of the cervical spine.
      Of the 47 headache sufferers, 17 also had weekly neck pain and 30 had neck pain
      less than once a month. MRI scans were interpreted independently by three
      neuroradiologists. Disc degeneration was found in 67% of participants, with no
      difference between adolescents with and without headache. Most of the
      degenerative changes were located in the lower cervical spine. In adolescence,
      mild degenerative changes of the cervical spine are surprisingly common but do
      not contribute to headache.

PMID- 17212679
TI  - A report of cranial autonomic symptoms in migraineurs.
AB  - The presence of cranial autonomic symptoms in migraine is well known and thought
      to represent activation of the trigeminal parasympathetic reflex pathway similar
      to trigeminal autonomic cephalalgias. However, studies regarding the prevalence
      of these symptoms are few. The characteristics of migraineurs with cranial
      autonomic symptoms and the association of cranial autonomic symptoms with
      laterality of headache have never been studied in a clinic population. Seventy
      eight consecutive subjects with migraine were recruited from the Headache Clinic
      of the Department of Psychiatry after exclusion of subjects with secondary
      headache. Their demographic data and detailed history of headache were noted and
      leading questions were asked regarding cranial autonomic symptoms. chi(2) test
      and Fisher's exact test was used for categorical variables, whereas an
      independent sample t-test was applied on numerical data. Spearman's correlation
      was used for correlational analysis of categorical variables. Female subjects
      (78.2%) outnumbered males and the average duration of illness in the whole sample
      was 3.81 years. Migraine without aura (53.8%) was the commonest diagnosis,
      followed by migraine with aura (24.4%). Cranial autonomic symptoms were present
      in 73.1% of subjects and, commonly, they were ipsilateral to headache. Moreover,
      strictly unilateral cranial autonomic symptoms were reported by only 32% of
      patients. The anatomical side of headache did not affect the presence of
      autonomic symptoms. Those with or without autonomic symptoms did not differ with
      respect to gender, diagnosis, laterality of headache or associated symptoms
      except phonophobia, which was more common in subjects with autonomic symptoms (P
      = 0.05). Those with autonomic symptoms had longer duration of illness (P = 0.03)
      and longer headache episodes (P = 0.04). In addition, sleep was ineffective in
      relieving their headache (P = 0.02). Cranial autonomic symptoms are frequent in
      migraineurs and are common in subjects with long duration of illness and longer
      headache episodes. Clinical evidence in the present study suggests that subjects
      with cranial autonomic symptoms have a hyperactive efferent arm of trigeminal
      autonomic reflex. The connections of trigeminal nucleus with the locus coeruleus
      and dorsal raphe nucleus may account for the observed phenotypic differences
      between the two groups. Further research, however, is required to elucidate the
      underlying neural mechanisms of cranial autonomic symptoms in migraine.

PMID- 17212680
TI  - Diclofenac epolamine is effective in the treatment of acute migraine attacks. A
      randomized, crossover, double blind, placebo-controlled, clinical study.
AB  - Hydrosoluble diclofenac epolamine (DHEP) represents an interesting approach to
      acute migraine attacks, where gastrointestinal motility and drug absorption are
      often reduced. Its efficacy was investigated in a randomized, crossover, double
      blind trial on 155 patients who treated four consecutive mild-to-moderate
      migraine attacks, either with DHEP (65-mg sachet) or placebo. If pain was not
      relieved within 1 h, a second dose was given. The total number of treated attacks
      was 481. A pain-free condition was achieved within 2 h in 45.8% and 25.1% of
      attacks treated, respectively, with DHEP or placebo (P < 0.0001), with a
      therapeutic gain of 20.7%. Time to attack resolution, light and noise sensitivity
      and impact on working ability were significantly reduced by DHEP compared with
      placebo. Moreover, significantly fewer patients required a second drug dose or a
      rescue medication when treated with DHEP than with placebo. No adverse reaction
      was recorded. In conclusion, DHEP was effective and safe for pain relief in
      patients with an acute mild-to-moderate migraine attack.

PMID- 17212681
TI  - Platelet glutamate uptake and release in migraine with and without aura.
AB  - Glutamate may play an important role in the pathogenesis of migraine: glutamate
      release in the brain may be involved in the development of spreading depression
      and increased concentrations of this amino acid have been reported in plasma and
      platelets from migraine patients. Here we assessed platelet glutamate uptake and
      release in 25 patients affected by migraine with aura (MA) and 25 patients
      affected by migraine without aura (MoA), comparing the results with a group of 20
      healthy matched controls. Both glutamate release from stimulated platelets and
      plasma concentrations of the amino acid were assessed by high-performance liquid
      chromatography, and were increased in both types of migraine, although more
      markedly in MA. Platelet glutamate uptake, assessed as 3H-glutamate intake, was
      increased in MA, while it was reduced in MoA with respect to the control group.
      These results support the view that MA might involve different pathophysiological
      mechanisms from MoA and, specifically, up-regulation of the glutamatergic
      metabolism. Understanding these dysfunctional pathways could lead to new,
      possibly more successful therapeutic approaches to the management of migraine.

PMID- 17212682
TI  - The impact of education on the diagnostic accuracy of tension-type headache and
      migraine: a prospective study.
AB  - General practitioners (GPs) diagnose and treat headache in primary care settings.
      The objective of this study was to investigate the effect of a 2-day headache
      education programme for GPs primarily on diagnostic accuracy. The education
      programme included theoretical lectures and face-to-face patient evaluation with
      headache specialists. Three GPs evaluated headache patients before and after the
      programme. Each GP was planned to interview a total of 60 patients (30 before, 30
      after the programme). All patients were evaluated by headache specialists
      following evaluation by the GPs. A total of 189 patients were included in this
      study. Diagnostic accuracy increased from 56.3% to 81.0% after the headache
      education programme (P < 0.001), which also significantly improved the choice of
      proper treatment (P = 0.043). The headache education programme for GPs
      significantly improved diagnostic accuracy in patients with tension-type headache
      and the choice of proper treatment. Such education programmes can be standardized
      and given to GPs working in the primary care setting. These programmes can be
      arranged locally by the universities and might have a favourable impact on the
      diagnosis and treatment of headache.

PMID- 17212683
TI  - Oestrogen-modulated increase of calmodulin-dependent protein kinase II (CamKII)
      in rat spinal trigeminal nucleus after systemic nitroglycerin.
AB  - Migraine can be triggered by systemic administration of the nitric oxide (NO)
      donor nitroglycerin (NTG) and by abrupt falls in plasma oestradiol. Calmodulin
      dependent protein kinase II (CamKII) present in superficial dorsal horns is
      thought to play a role in sensitization of central nociceptors, a phenomen
      present in migraineurs. We therefore examined in rats the expression of CamKII in
      the caudal trigeminal nucleus (TNC) after subcutaneous NTG (10 mg/kg) and its
      modulation by oestrogen. In male rats and in ovariectomized females, after 4 h
      NTG increased significantly CamKII expression in the superficial layers of TNC,
      but not in the upper thoracic spinal cord. NTG had no effect on CamKII expression
      in oestradiol-treated ovariectomized animals. Thus NTG, i.e. NO, selectively
      enhances CamKII in the rat TNC and oestradiol blocks this effect. These data may
      help to understand the mechanisms by which NO triggers migraine attacks and
      oestrogens influence migraine severity.

PMID- 17212684
TI  - The cost-effectiveness of oral triptan therapy in Sweden.
AB  - The literature suggests that triptans are cost effective compared with older
      types of migraine treatment. However, which of the triptans that is most cost
      effective has not been established. We compared the costs and effects of triptan
      treatment from a Swedish societal perspective, using evidence from the
      literature. A probabilistic cost-effectiveness model was constructed to
      investigate the costs and effects of treating a single attack in a typical
      migraine patient. The end-point used in the base-case analysis was sustained pain
      free without any adverse events (SNAE). We searched the scientific literature for
      meta-analyses reporting the efficacy of oral triptans. All treatments except
      rizatriptan 10 mg and eletriptan 40 mg were dominated. The incremental cost per
      SNAE of rizatriptan 10 mg compared with eletriptan 40 mg was approximately 100
      euro. There was substantial uncertainty concerning the results, but probabilistic
      analysis showed that rizatriptan 10 mg and eletriptan 40 mg had the highest
      probability of being cost-effective.

PMID- 17212685
TI  - Sympathy for Pontius Pilate. Hemicrania in M. A. Bulgakov's The Master and
      Margarita.
AB  - The aim of this study was to explore the description of the migraine attack of
      Pontius Pilate (a character in the novel The Master and Margarita by M. A.
      Bulgakov). Some of its features are analysed in light of current migraine
      literature. It is hypothesized that, at least in part, this description is based
      on the personal experience of the novel's author. We studied and analysed the
      text of the novel, other works by Bulgakov, his biography, including his medical
      training and practice, and the recently published diaries of Bulgakov and his
      wife E. S. Bulgakova. The novel contains a comprehensive description of a
      migraine attack. It includes a prodrome/aura of osmophobia. Olfactory perception
      during or shortly before the migraine attack is altered to the point where
      neutral or even pleasant odours become unbearable. Bulgakov's extensive history
      of migraines is seen in his diary, the diary of his wife, letters and other
      literary works. This is one of the most detailed and extensive depictions of a
      migraine attack in literature, with osmophobia described with great emphasis. It
      is likely that Pilate's migraine is described based on the personal history of
      the novel's author.

PMID- 17212686
TI  - Bayard Horton's clinicopathological description of giant cell (temporal)
      arteritis.
AB  - The author set out to review the thought processes of Bayard Horton as he was
      clinicopathologically describing the first cases of temporal arteritis. The Mayo
      Clinic records of the original temporal arteritis patients were examined. Horton
      obtained the first biopsies of the temporal arteries in temporal arteritis and
      was the first to describe the histopathology. Horton initially thought his first
      two patients had actinomycosis of the temporal arteries, but later abandoned this
      diagnosis. He reported these two patients in 1932 as 'an undescribed form of
      arteritis of the temporal vessels'. He was the first to describe jaw
      claudication. He saw a patient with blindness and symptoms suggestive of temporal
      arteritis before this complication was described in the literature, but initially
      felt the patient had some other disease. The sedimentation rate was elevated in
      his first patient. He cared for the first temporal arteritis patient ever treated
      with cortisone.

PMID- 17212687
TI  - SUNCT syndrome in a patient with prolactinoma and cabergoline-induced attacks.
AB  - Short-lasting unilateral neuralgiform headache with conjuntival injection and
      tearing (SUNCT) syndrome is a rare trigeminal autonomic cephalalgia. We report a
      patient with prolactinoma and cabergoline-induced SUNCT attacks and the
      literature is reviewed for a better understanding of the pathophysiology.

PMID- 17212688
TI  - Cerebral sinus thrombosis presenting with cluster-like headache.

PMID- 17212689
TI  - Non-REM hypnic headache: a circadian disorder? A clinical and polysomnographic
      study.

PMID- 17212690
TI  - A case of spontaneous intracranial hypotension complicated by isolated cortical
      vein thrombosis and cerebral venous infarction.

PMID- 17212691
TI  - Oxcarbazepine-induced headache.

PMID- 17212693
TI  - Hemifacial spasm and cluster headache.

PMID- 17212694
TI  - Excessive hippocampal acetylcholine levels in acetylcholinesterase-deficient mice
      are moderated by butyrylcholinesterase activity.
AB  - Central cholinergic systems are involved in a plethora of brain functions and are
      severely and selectively damaged in neurodegenerative diseases such as
      Alzheimer's disease and dementia with Lewy bodies. Cholinergic dysfunction is
      treated with inhibitors of acetylcholinesterase (AChE) while the role of
      butyrylcholinesterase (BChE) for brain cholinergic function is unclear. We have
      used in vivo microdialysis to investigate the regulation of hippocampal
      acetylcholine (ACh) levels in mice that are devoid of AChE (AChE-/- mice).
      Extracellular ACh levels in the hippocampus were 60-fold elevated in AChE-/- mice
      compared with wild-type (AChE+/+) animals. In AChE-/- mice, calcium-free
      conditions reduced hippocampal ACh levels by 50%, and infusion of tetrodotoxin by
      more than 90%, indicating continuous ACh release. Infusion of a selective AChE
      inhibitor (BW284c51) caused a dose-dependent, up to 16-fold increase of
      extracellular ACh levels in AChE+/+ mice but did not change ACh levels in AChE-/-
      mice. In contrast, infusion of a selective inhibitor of BChE (bambuterol) caused
      up to fivefold elevation of ACh levels in AChE-/- mice, but was without effect in
      AChE+/+ animals. These results were corroborated with two other specific
      inhibitors of AChE and BChE, tolserine and bis-norcymserine, respectively. We
      conclude that lack of AChE causes dramatically increased levels of extracellular
      ACh in the brain. Importantly, in the absence of AChE, the levels of
      extracellular ACh in the brain are controlled by the activity of BChE. These
      results point to a potential usefulness of BChE inhibitors in the treatment of
      central cholinergic dysfunction in which brain AChE activity is typically
      reduced.

PMID- 17212695
TI  - Activation of GABA(A) receptors facilitates astroglial differentiation induced by
      ciliary neurotrophic factor in neural progenitors isolated from fetal rat brain.
AB  - Immunocytochemical analysis confirmed the validity of isolation procedures of
      neural progenitors capable of self-replication and differentiation from discrete
      fetal rat brain structures. A reverse transcription-polymerase chain reaction
      analysis revealed the expression of particular GABA(A) receptor (GABA(A)R),
      GABA(B)R-1 and GABA(C)R, but not GABA(B)R-2, subunits in neocortical cells before
      commitment. Sustained exposure to the GABA(A)R agonist muscimol at 100 mumol/L
      led to significant increases in the mitochondrial activity and the total areas of
      neocortical neurospheres formed during the cultivation for 12 days in a manner
      sensitive to a GABA(A)R antagonist, with lactate dehydrogenase release being
      unchanged. Moreover, prior sustained exposure to muscimol significantly
      facilitated the subsequent expression of an astroglial marker protein in cells
      differentiated by ciliary neurotrophic factor (CNTF) toward an astroglial
      lineage, with a concomitant decrease in the neuronal marker protein expression,
      in an antagonist-sensitive manner on Western blotting analysis. However, muscimol
      failed to significantly affect the expression of both marker proteins in cells
      differentiated in either the presence or absence of all-trans-retinoic acid.
      These results suggest that prior activation of GABA(A)R may preferentially
      facilitate the commitment by CNTF of neural progenitor cells toward an astroglial
      lineage after simulation of the self-replication activity in the developing rat
      brain.

PMID- 17212696
TI  - GAP-43 regulates NCAM-180-mediated neurite outgrowth.
AB  - The neural cell adhesion molecule (NCAM), and the growth-associated protein (GAP
      43), play pivotal roles in neuronal development and plasticity and possess
      interdependent functions. However, the mechanisms underlying the functional
      association of GAP-43 and NCAM have not been elucidated. In this study we show
      that (over)expression of GAP-43 in PC12E2 cells and hippocampal neurons strongly
      potentiates neurite extension, both in the absence and in the presence of
      homophilic NCAM binding. This potentiation is crucially dependent on the membrane
      association of GAP-43. We demonstrate that phosphorylation of GAP-43 by protein
      kinase C (PKC) as well as by casein kinase II (CKII) is important for the NCAM
      induced neurite outgrowth. Moreover, our results indicate that in the presence of
      GAP-43, NCAM-induced neurite outgrowth requires functional association of NCAM
      180/spectrin/GAP-43, whereas in the absence of GAP-43, the NCAM-140/non-receptor
      tyrosine kinase (Fyn)-associated signaling pathway is pivotal. Thus, expression
      of GAP-43 presumably acts as a functional switch for NCAM-180-induced signaling.
      This suggests that under physiological conditions, spatial and/or temporal
      changes of the localization of GAP-43 and NCAM on the cell membrane may determine
      the predominant signaling mechanism triggered by homophilic NCAM binding: NCAM
      180/spectrin-mediated modulation of the actin cytoskeleton, NCAM-140-mediated
      activation of Fyn, or both.

PMID- 17212697
TI  - Hydrogen sulfide attenuates lipopolysaccharide-induced inflammation by inhibition
      of p38 mitogen-activated protein kinase in microglia.
AB  - The present study attempts to investigate the effect of H(2)S on
      lipopolysaccharide (LPS)-induced inflammation in both primary cultured microglia
      and immortalized murine BV-2 microglial cells. We found that exogenous
      application of sodium hydrosulfide (NaHS) (a H(2)S donor, 10-300 micro mol/L)
      attenuated LPS-stimulated nitric oxide (NO) in a concentration-dependent manner.
      Stimulating endogenous H(2)S production decreased LPS-stimulated NO production,
      whereas lowering endogenous H(2)S level increased basal NO production. Western
      blot analysis showed that both exogenous and endogenous H(2)S significantly
      attenuated the stimulatory effect of LPS on inducible nitric oxide synthase
      expression, which is mimicked by SB 203580, a specific p38 mitogen-activated
      protein kinase (MAPK) inhibitor. Exogenously applied NaHS significantly
      attenuated LPS-induced p38 MAPK phosphorylation in BV-2 microglial cells.
      Moreover, both NaHS (300 micro mol/L) and SB 203580 (1 micro mol/L) significantly
      attenuated LPS-induced tumor necrosis factor-alpha secretion, another
      inflammatory indicator. In addition, NaHS (10-300 micro mol/L) dose-dependently
      decreased LPS-stimulated NO production in primary cultured astrocytes, suggesting
      that the anti-neuroinflammatory effect of H(2)S is not specific to microglial
      cells alone. Taken together, H(2)S produced an anti-inflammatory effect in LPS
      stimulated microglia and astrocytes, which may be due to inhibition of inducible
      nitric oxide synthase and p38 MAPK signaling pathways. These findings may have
      important implications in the treatment of neuroinflammation-related diseases.

PMID- 17212698
TI  - Modulation of the kinetics of evoked quantal release at mouse neuromuscular
      junctions by calcium and strontium.
AB  - The effects of calcium and strontium on the quantal content of nerve-evoked
      endplate currents and on the kinetic parameters of quantal release (minimal
      synaptic delay, value of main mode of synaptic delay histogram, and variability
      of synaptic delay) were studied at the mouse neuromuscular synapse. At low
      calcium ion concentrations (0.2-0.6 mmol/L), evoked signals with long synaptic
      delays (several times longer than the value of main mode) were observed. Their
      number decreased substantially when [Ca(2+)](o) was increased (i.e. the release
      of transmitter became more synchronous). By contrast, the early phase of
      secretion, characterized by minimal synaptic delay and accounting for the main
      peak of the synaptic delay histogram, did not change significantly with
      increasing [Ca(2+)](o). Hence, extracellular calcium affected mainly the late,
      'asynchronous', portion of phasic release. The average quantal content grew
      exponentially from 0.09 +/- 0.01 to 1.04 +/- 0.07 with the increase in
      [Ca(2+)](o) without reaching saturation. Similar results were obtained when
      calcium was replaced by strontium, but the asynchronous portion of phasic release
      was more pronounced and higher strontium concentrations (to 1.2-1.4 mmol/L) were
      required to abolish responses with long delays. Treatment of preparations with
      1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl
      ester (BAPTA-AM) (25 micromol/L), but not with ethylene glycol-bis(2
      aminoethylether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester (EGTA-AM) (25
      micromol/L), abolished the responses with long delays. The dependence of quantal
      content and synchrony of quantal release on calcium and strontium concentrations
      have quite different slopes, suggesting that they are governed by different
      mechanisms.

PMID- 17212699
TI  - The evolutionary history and tissue mapping of GPR123: specific CNS expression
      pattern predominantly in thalamic nuclei and regions containing large pyramidal
      cells.
AB  - The Adhesion family of G protein-coupled receptors (GPCRs) includes 33 receptors
      and is the second largest GPCR family. Most of these proteins are still orphans
      and fairly little is known of their tissue distribution and evolutionary context.
      We report the evolutionary history of the Adhesion family protein GPR123 as well
      as mapping of GPR123 mRNA expression in mouse and rat using in situ hybridization
      and real-time PCR, respectively. GPR123 was found to be well conserved within the
      vertebrate lineage, especially within the transmembrane regions and in the distal
      part of the cytoplasmic tail, containing a potential PDZ binding domain. The real
      time PCR data indicates that GPR123 is predominantly expressed in CNS. The in
      situ data show high expression in thalamic nuclei and regions containing large
      pyramidal cells like cortex layers 5 and 6 and subiculum. Moreover, we found
      distinct expression in amygdala, hypothalamus, inferior olive and spinal cord.
      The CNS specific expression, together with the high sequence conservation between
      the vertebrate sequences investigated, indicate that GPR123 may have an important
      role in the regulation of neuronal signal transduction.

PMID- 17212700
TI  - Serotonin and epilepsy.
AB  - In recent years, there has been increasing evidence that serotonergic
      neurotransmission modulates a wide variety of experimentally induced seizures.
      Generally, agents that elevate extracellular serotonin (5-HT) levels, such as 5
      hydroxytryptophan and serotonin reuptake blockers, inhibit both focal and
      generalized seizures, although exceptions have been described, too. Conversely,
      depletion of brain 5-HT lowers the threshold to audiogenically, chemically and
      electrically evoked convulsions. Furthermore, it has been shown that several anti
      epileptic drugs increase endogenous extracellular 5-HT concentration. 5-HT
      receptors are expressed in almost all networks involved in epilepsies. Currently,
      the role of at least 5-HT(1A), 5-HT(2C), 5-HT(3) and 5-HT(7) receptor subtypes in
      epileptogenesis and/or propagation has been described. Mutant mice lacking 5
      HT(1A) or 5-HT(2C) receptors show increased seizure activity and/or lower
      threshold. In general, hyperpolarization of glutamatergic neurons by 5-HT(1A)
      receptors and depolarization of GABAergic neurons by 5-HT(2C) receptors as well
      as antagonists of 5-HT(3) and 5-HT(7) receptors decrease the excitability in
      most, but not all, networks involved in epilepsies. Imaging data and analysis of
      resected tissue of epileptic patients, and studies in animal models all provide
      evidence that endogenous 5-HT, the activity of its receptors, and pharmaceuticals
      with serotonin agonist and/or antagonist properties play a significant role in
      the pathogenesis of epilepsies.

PMID- 17212702
TI  - Immune regulation by mesenchymal stem cells: two sides to the coin.
AB  - Mesenchymal stem cells (MSCs) constitute a rare population of adult stem cells
      that can be isolated from a simple bone marrow aspirate in the absence of prior
      mobilization. For this reason, MSCs are particularly attractive for cell-based
      medicine. Ex-vivo-expanded MSCs isolated from different species, including human
      MSCs, have been shown to suppress the activity of a broad range of immune cells,
      including T cells, antigen-presenting cells, natural killer (NK) cells and B
      cells. New studies have further shown that MSCs interact with NK cells, express
      NK cell receptor ligands, express Toll-like receptors (TLRs), respond to TLR
      ligands and act as antigen-presenting cells upon interferon-gamma stimulation.
      Taken together, these studies suggest that MSCs may constitute a previously
      unrecognized player of the immune system with dichotomy of function reminiscent
      of other antigen-presenting cells. An important question that remains unanswered
      is whether resident MSCs actually play a role in endogenous immune responses? I
      here review the mechanisms of MSC-mediated immune regulation and discuss the
      major roles of resident MSCs in health and disease.

PMID- 17212703
TI  - Molecular genetic studies of natives on Easter Island: evidence of an early
      European and Amerindian contribution to the Polynesian gene pool.
AB  - Most archaeological and linguistic evidence suggest a Polynesian origin of the
      population of Easter Island (Rapanui), and this view has been supported by the
      identification of Polynesian mitochondrial DNA (mtDNA) polymorphisms in
      prehistoric skeletal remains. However, some evidence of an early South American
      contact also exists (the sweet potato, bottle gourd etc.), but genetic studies
      have so far failed to show an early Amerindian contribution to the gene pool on
      Easter Island. To address this issue, we analyzed mtDNA and Y chromosome markers
      and performed high-resolution human leukocyte antigen (HLA) genotyping of DNA
      harvested from previously collected sera of 48 reputedly nonadmixed native Easter
      Islanders. All individuals carried mtDNA types and HLA alleles previously found
      in Polynesia, and most men carried Y chromosome markers of Polynesian origin,
      providing further evidence of a Polynesian origin of the population of Easter
      Island. A few individuals carried HLA alleles and/or Y chromosome markers of
      European origin. More interestingly, some individuals carried the HLA alleles
      A*0212 and B*3905, which are of typical Amerindian origin. The genealogy of some
      of the individuals carrying these non-Polynesian HLA alleles and their haplotypic
      backgrounds suggest an introduction into Easter Island in the early 1800s, or
      earlier. Thus, there may have been an early European and Amerindian contribution
      to the Polynesian gene pool of Easter Island.

PMID- 17212701
TI  - Macrophages are comprised of resident brain microglia not infiltrating peripheral
      monocytes acutely after neonatal stroke.
AB  - Macrophages can be both beneficial and detrimental after CNS injury. We
      previously showed rapid accumulation of macrophages in injured immature brain
      acutely after ischemia-reperfusion. To determine whether these macrophages are
      microglia or invading monocytes, we subjected post-natal day 7 (P7) rats to
      transient 3 h middle cerebral artery (MCA) occlusion and used flow cytometry at
      24 and 48 h post-reperfusion to distinguish invading monocytes (CD45high/CD11b+)
      from microglia (CD45low/medium/CD11b+). Inflammatory cytokines and chemokines
      were determined in plasma, injured and contralateral tissue 1-24 h post
      reperfusion using ELISA-based cytokine multiplex assays. At 24 h, the number of
      CD45+/CD11b+ cells increased 3-fold in injured compared to uninjured brain tissue
      and CD45 expression shifted from low to medium with less than 10% of the
      population expressing CD45high. MCA occlusion induced rapid and transient
      asynchronous increases in the pro-inflammatory cytokine IL-beta and chemokines
      cytokine-induced neutrophil chemoattractant protein 1 (CINC-1) and monocyte
      chemoattractant protein 1 (MCP-1), first in systemic circulation and then in
      injured brain. Double immunofluorescence with cell-type specific markers showed
      that multiple cell types in the injured brain produce MCP-1. Our findings show
      that despite profound increases in MCP-1 in injured regions, monocyte
      infiltration is low and the majority of macrophages in acutely injured regions
      are microglia.

PMID- 17212705
TI  - CD31/PECAM-1 genotyping and haplotype analyses show population diversity.
AB  - Using direct sequencing of complementary DNA products, the sequences of human
      CD31 from exon 1 through exon 16 of 179 individuals (139 unrelated) were
      systematically examined. Of the 14 biallelic single nucleotide polymorphic sites
      detected, 7 polymorphic sites involved amino acid substitution. These 14
      polymorphic sites yielded 18 observed CD31 alleles and 9 predicted CD31
      polypeptide sequences. Based on molecular haplotyping and family pedigree
      analysis, linkage disequilibrium among some single nucleotide polymorphic sites
      was observed. Single nucleotide polymorphism frequencies between populations were
      also measured using dot-blot hybridization with DNA or peptide nucleic acid
      probes.

PMID- 17212704
TI  - PD-L1 expression analysis in gastric carcinoma tissue and blocking of tumor
      associated PD-L1 signaling by two functional monoclonal antibodies.
AB  - Programmed death-1 ligand-1 (PD-L1), a member of the B7 family of costimulatory
      molecules, plays an important role in the regulations of the cellular and humoral
      immune responses. In this study, two mouse anti-human PD-L1 monoclonal antibodies
      named 10E10 and 2H11 were successfully generated and further characterized.
      Monoclonal antibody 10E10 bound to distinct PD-L1 epitope comparing an available
      anti-PD-L1 monoclonal antibody on a series of malignant cell lines, activated T
      lymphocytes, B lymphocytes and dendritic cells. Then, by using
      immunohistochemistry staining with monoclonal antibody 2H11, the expression of PD
      L1 was found in human gastric carcinoma specimens but not in normal or gastric
      adenoma tissues. Additional data show that PD-L1 can be regarded as a decisive
      factor in evaluating gastric carcinoma prognosis and anti-human PD-L1 monoclonal
      antibody 10E10 could inhibit T-cell apoptosis induced by tumor-associated PD-L1.
      Taken together, these results showed that the two functional mouse anti-human PD
      L1 monoclonal antibodies we generated might be of great value for further
      exploration of the costimulatory molecule regulating network and
      immunointervention for tumor immunotherapy.

PMID- 17212706
TI  - Childhood asthma and human leukocyte antigen type.
AB  - Little is known about the relationship between human leukocyte antigen (HLA)
      class II genes and family history of asthma or atopy in relation to the incidence
      of childhood asthma. The objective of the study was to determine whether specific
      HLA class II genes (e.g., DRB1*03) are associated with asthma and whether such
      association explains the influences of family history of asthma or atopy on
      asthma incidence. A stratified random sample of 340 children who had HLA data
      available from the Rochester Family Measles Study cohort (n= 876) and a
      convenience sample of healthy children aged 5-12 years were the participants. We
      conducted comprehensive medical record reviews to determine asthma status of
      these children. The associations between the presence of specific HLA alleles and
      development of asthma and the role of family history of asthma or atopy in the
      association were evaluated by fitting Cox models. The cumulative incidence of
      asthma by 12 years of age among children who carry HLA DRB1*03 was 33%, compared
      to 24.2% among those who did not carry this allele. Adjusting for family history
      of asthma or atopy, gender, low birth weight, season of birth, HLA DRB1*04, and
      HLA DQB1*0302, the hazards ratio for HLA DRB1*03 carriers was 1.8 (95% confidence
      interval: 1.1-2.9, P= 0.020). We concluded that the HLA DRB1*03 allele is
      associated with asthma. However, the HLA class II gene does not explain the
      influences of family history of asthma or atopy on development of asthma. The
      mechanism underlying the association between asthma and HLA genes needs to be
      elucidated.

PMID- 17212707
TI  - Human MHC region harbors both susceptibility and protective haplotypes for
      coronary artery disease.
AB  - Aiming to study the role of human major histocompatibility complex (MHC) region
      on coronary artery disease (CAD), we enrolled two separate patient materials and
      controls. First, heart transplantation recipients (n = 276) were divided into
      three subgroups according to the severity of atherosclerosis. The human leukocyte
      antigen (HLA)-A-B-DR haplotype and gene frequencies were compared between groups.
      Second, patients with acute coronary syndrome (ACS) (n = 100) and healthy
      controls (n = 74) were assessed by nine genetic MHC markers (HLA-A, HLA-B, HLA
      DRB1, LTA+253(a/g), LTA+496(C/T), LTA+633(c/g), LTA+724(C/A), C4A and C4B), and
      the frequencies were compared. In the heart transplantation recipients, HLA-DR1
      was strongly associated with CAD [severe vs no evidence, odds ratio (OR) 2.37;
      95% confidence interval (CI) 1.33-4.25; P = 0.003]. Similarly, in the patients
      with ACS, HLA-DRB1*01 was associated with CAD (patients vs controls, OR 2.36; 95%
      CI 1.25-4.44; P = 0.007). HLA-DRB1*01 was associated with low-density-lipoprotein
      cholesterol (OR 5.32; 95% CI 1.64-17.26; P = 0.005) and smoking habit (OR 3.13;
      95% CI 1.09-9.03; P = 0.035) as risk factors. The strongest protective gene was
      HLA-B*07 alone (OR 0.46; 95% CI 0.24-0.88; P = 0.02) or together with the
      haplotype LTA+253a-LTA+633g-C4A3-C4B1 (OR 0.36; 95% CI 0.22-0.57; P = 0.00001).
      In conclusion, human MHC region harbors genes that protect from and predispose to
      CAD.

PMID- 17212708
TI  - Kappa immunoglobulin light chain polymorphisms and survival after allogeneic
      transplantation for B-cell malignancies: a potential graft-vs-leukaemia target.
AB  - In the human leucocyte antigen (HLA)-matched haematopoietic stem cell
      transplantation (HSCT) setting, minor histocompatibility antigen (mHA)
      disparities between recipient and donor can lead to graft-vs-host disease (GVHD)
      or graft rejection. Graft-vs-leukaemia (GVL) effect is a beneficial T-cell
      mediated immune response that can also occur following HLA-matched HSCT. mHAs
      with tissue expression restricted to cells of the haematopoietic system are
      particularly relevant as immunotherapeutic targets for destroying malignant cells
      without inducing GVHD. Therefore, it is important to identify further
      haematopoietic-restricted polymorphic mHAs, which may have the potential to be
      used clinically for adoptive immunotherapy. Polymorphic mismatching of minor
      antigens, such as the B-cell-specific protein, the kappa immunoglobulin light
      chain (kappa) may play a role in the incidence of GVL and therefore the survival
      of transplant recipients following transplantation for B-cell malignancies.
      Polymorphisms in the constant region of the immunoglobulin kappa polypeptide
      chain have been defined involving single amino acid changes at positions 153 and
      191. In this study, 51 HLA-matched B-cell malignancy transplant pairs were kappa
      typed by polymerase chain reaction and restriction enzyme digestion to
      investigate the association between kappa allotype disparity and outcome after
      transplantation. Kappa allotype disparity between transplant pairs may be
      associated with an increased survival compared with pairs not mismatched for
      kappa, as kappa mismatched recipients had a higher percentage of complete
      remissions and a decreased level of relapse in comparison with the nonmismatched
      recipients. HLA peptide prediction software was used to determine which HLA types
      were the best binders for kappa peptides. It was observed that patients with
      tissue types predicted to bind the kappa Km(1,2) peptides had better survival
      outcomes and no relapse compared with those with tissue types not predicted to
      bind the kappa Km(1,2) peptides. This study may contribute to the assessment of
      the clinical role of kappa with regard to the outcome of allogeneic
      transplantation for B-cell malignancies.

PMID- 17212709
TI  - The expression analysis of ICOS-L on activated T cells and immature dendritic
      cells as well as malignant B cells and Grave's-disease-derived thyroid tissues by
      two novel mAbs against human ICOS-L.
AB  - ICOS-L, a newly identified member of B7 superfamily, plays an important role in
      immune responses. In this article, we report on two novel mouse anti-human ICOS-L
      monoclonal antibodies (mAbs) named as 11C4 and 12B11, whose specificities were
      verified by methods of flow cytometry, western blotting, and epitope competition
      assay. The two mAbs bound to distinct ICOS-L epitopes on B cells. Interestingly,
      mAb 11C4 could well recognize ICOS-L molecule on activated T cells and Jurkat
      cell lines, which is different from commercial anti-ICOS-L mAb (clone number
      MIH12) and the other mAb 12B11. In addition, we found that the expression of ICOS
      L molecule was only detected on the surface of immature monocyte-derived
      dendritic cells (Mo-DCs) and was sharply decreased after induction of mature Mo
      DCs activated by tumor necrosis factor-alpha or CD40. Furthermore, we showed that
      11C4 could effectively suppress the maturation of Mo-DCs in vitro as evidenced by
      the low expression of CD80, CD86, CD83, and human leukocyte antigen-DR, which
      suggested that ICOS-L may be involved in the maturation of Mo-DCs. Using
      immunohistochemistry staining with mAb 11C4, the expression of ICOS-L was found
      in B lymphoma tissues and thyroid tissues from the Grave's disease but not in
      thyroid adenoma and normal thyroid tissues.

PMID- 17212710
TI  - HLA-A, -B, -C, -DRB1 allele and haplotype frequencies in an African American
      population.
AB  - Sequence-based typing was used to identify human leukocyte antigen (HLA)-A, -B, 
      C, and -DRB1 alleles from 564 consecutively recruited African American volunteers
      for an unrelated hematopoietic stem cell registry. The number of known alleles
      identified at each locus was 42 for HLA-A, HLA-B 67, HLA-C 33, and HLA-DRB1 44.
      Six novel alleles (A*260104, A*7411, Cw*0813, Cw*1608, Cw*1704, and DRB1*130502)
      not observed in the initial sequence-specific oligonucleotide probe testing were
      characterized. The action of balancing selection, shaping more 'even' than
      expected allele frequency distributions, was inferred for all four loci and
      significantly so for the HLA-A and DRB1 loci. Two-, three-, and four-locus
      haplotypes were estimated using the expectation maximization algorithm.
      Comparisons with other populations from Africa and Europe suggest that the degree
      of European admixture in the African American population described here is lower
      than that in other African American populations previously reported, although HLA
      A:B haplotype frequencies similar to those in previous studies of African
      American individuals were also noted.

PMID- 17212711
TI  - Linkage disequilibria between human leucocyte antigen-B and closely linked
      microsatellites in the Croatian population.
AB  - The aim of the present study was to investigate polymorphism of D6S2927,
      STR_MICA, D6S2793, TNFa (D6S2792), TNFb and TNFd (D6S2789) microsatellites and
      linkage disequilibria between these loci and human leucocyte antigen (HLA)-B
      (previously tested) for better characterisation of extended HLA haplotypes. A
      total of 176 healthy unrelated Croatians were studied using polymerase chain
      reaction amplification and electrophoresis on 6% polyacrylamide gel in ALFexpress
      sequencer. Eight HLA-B/D6S2927 haplotypic associations (B*07/D6S2927-4,
      B*08/D6S2927-3, B*18/D6S2927-3, B*27/D6S2927-1, B*35/D6S2927-5, B*38/D6S2927-4,
      B*51/D6S2927-2 and B*61/D6S2927-1) showed strong association (P < 0.001, D >
      0.5). Among 88 different HLA-B/STR_MICA haplotypic associations, seven
      combinations (B*07/STR_MICA-A5.1, B*08/STR_MICA-A5.1, B*15/STR_MICA-A5,
      B*18/STR_MICA-A4, B*27/STR_MICA-A4, B*38/STR_MICA-A9 and B*51/STR_MICA-A6)
      demonstrated high linkage (D> or = 0.3) with significant P value (P < 0.001).
      Strong associations were also observed for five HLA-B/D6S2793 haplotypes
      (B*07/D6S2793-CA17, B*08/D6S2793-CA24, B*13/D6S2793-CA18, B*14/D6S2793-CA14 and
      B*27/D6S2793-CA14). HLA-B*08/TNFb3 and HLA-B*50/TNFb7 were the strongest
      associations for HLA-B/TNFb. Nine HLA-B/TNFa combinations were observed with
      significant P value (B*07/TNFa11, B*08/TNFa2, B*13/TNFa7, B*18/TNFa10,
      B*27/TNFa6, B*37/TNFa9, B*38/TNFa10, B*39/TNFa13 and B*44/TNFa4). Out of six HLA
      B/TNFd haplotypic associations with strong D value, HLA-B*08/TNFd2 and B*37/TNFd3
      showed the highest statistical significance (P < 0.0001). These results provide
      data on the region around the HLA-B that is very attractive because of its
      contribution to genetic susceptibility for many HLA-associated diseases and
      therefore this information will help in all further HLA-B locus-associated
      disease studies.

PMID- 17212712
TI  - Expression of APOBEC3G in kidney cells.
AB  - The apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G
      (APOBEC3G), a member of the APOBEC family possessing DNA mutator activity through
      cytosine deamination, is reported to play an important role in host defense
      against infections such as those of hepatitis B virus and human immunodeficiency
      virus. Here, we examined the expression of APOBEC3G in human kidney cells to
      better understand its biological role against infection. APOBEC3G was
      immunohistochemically detectable in kidney mesangial cells and also to some
      extent in kidney epithelial tubular cells. In addition, overexpression of
      APOBEC3G was shown in renal carcinoma tissues and cell lines. APOBEC3G expression
      was upregulated by inflammatory cytokines, such as interferon, interleukin-6, and
      tumor necrosis factor. These results may provide new insight into the role of
      APOBEC3G in host defense against viral infection and cancer.

PMID- 17212713
TI  - Sequencing of a novel HLA-A allele, A*6836, showing a Bw4 epitope.
AB  - A novel A*6836 allele was completely characterized by sequence-based typing (SBT)
      in a cord blood sample from an Ecuadorian donor. A*6836 discloses six clustered
      amino acid residue changes at the alpha-1 domain, codons 76-83, regarding its
      closer A*680102 allele. Therefore, A*6836 would be a new human leukocyte antigen
      (HLA)-A molecule showing a Bw4-epitope.

PMID- 17212714
TI  - HLA-Cw*0740, a new allele mistyped by generic sequencing and identified by
      allelic separation.
AB  - Human leukocyte antigen (HLA)-Cw*0740 differs from HLA-Cw*070101 by one
      nucleotide substitution at codon 73 (GCT>ACT).

PMID- 17212715
TI  - A novel HLA-DQB1*06 allele, DQB1*0628, found through routine sequence-based HLA
      typing and confirmation of DQB1*060302.
AB  - In this paper we report the identification of human leukocyte antigen (HLA)
      DQB1*0628 and the confirmation of HLA-DQB1*060302.

PMID- 17212717
TI  - In vivo recovery of factor VIII and factor IX: intra- and interindividual
      variance in a clinical setting.
AB  - In vivo recovery (IVR) is traditionally used as a parameter to characterize the
      pharmacokinetic properties of coagulation factors. It has also been suggested
      that dosing of factor VIII (FVIII) and factor IX (FIX) can be adjusted according
      to the need of the individual patient, based on an individually determined IVR
      value. This approach, however, requires that the individual IVR value is more
      reliably representative for the patient than the mean value in the population,
      i.e. that there is less variance within than between the individuals. The aim of
      this investigation was to compare intra- and interindividual variance in IVR (as
      U dL1 per U kg1) for FVIII and plasma-derived FIX in a cohort of non-bleeding
      patients with haemophilia. The data were collected retrospectively from six
      clinical studies, yielding 297 IVR determinations in 50 patients with haemophilia
      A and 93 determinations in 13 patients with haemophilia B. For FVIII, the mean
      variance within patients exceeded the between-patient variance. Thus, an
      individually determined IVR value is apparently no more informative than an
      average, or population, value for the dosing of FVIII. There was no apparent
      relationship between IVR and age of the patient (1.5-67 years). For FIX, the mean
      variance within patients was lower than the between-patient variance, and there
      was a significant positive relationship between IVR and age (13-69 years). From
      these data, it seems probable that using an individual IVR confers little
      advantage in comparison to using an age-specific population mean value. Dose
      tailoring of coagulation factor treatment has been applied successfully after
      determination of the entire single-dose curve of FVIII:C or FIX:C in the patient
      and calculation of the relevant pharmacokinetic parameters. However, the findings
      presented here do not support the assumption that dosing of FVIII or FIX can be
      individualized on the basis of a clinically determined IVR value.

PMID- 17212718
TI  - Evaluation of pharmacokinetics, efficacy and safety of Immunate solvent detergent
      in previously treated patients with severe haemophilia A.
AB  - Immunate Solvent Detergent (S/D) is a plasma derived, purified, human factor VIII
      (FVIII) - von Willebrand factor (VWF) complex subjected to two virus
      inactivation/removal processes: S/D and vapor heat treatment. This prospective,
      multicentre, three-part clinical study evaluated the pharmacokinetics (in
      comparison to the predecessor product Immunate), efficacy and safety of Immunate
      S/D in 56 previously treated patients with severe haemophilia A. Subjects
      received Immunate S/D on-demand, as a prophylactic regimen or both. The results
      of the pharmacokinetic population demonstrate that Immunate and Immunate S/D were
      equivalent with respect to the FVIII - and to the retrospectively VWF -
      parameters assessed. A total of 623 bleeding episodes were reported in 47/56
      subjects. The duration of prophylaxis ranged from 0.1-5.2 months with a total of
      175.6 months. The median number of bleeds per month in subjects on prophylaxis
      was 0 (range 0-10). Ninety-six percent of bleeding episodes were rated as having
      an excellent or good response. For most bleeding episodes (89%), subjects
      required only one infusion with a mean dose of 29.6 IU kg(-1). No FVIII
      inhibitory antibodies were observed in any subject. No related serious adverse
      events were reported. Thus, the introduction of S/D treatment did not alter the
      PK characteristics and function of VWF and FVIII molecules of Immunate S/D which
      is effective and safe for treatment of bleeding episodes, management of surgical
      procedures, and prophylaxis.

PMID- 17212719
TI  - Definitions for haemophilia prophylaxis and its outcomes: the Canadian consensus
      study.
AB  - The creation of acceptable standard definitions for terms used in the care and
      assessment of haemophilia patients has become increasingly important, as a
      growing number of international clinical studies have been initiated. The Delphi
      approach has been used in health research to reach consensus in large groups and
      can be used to develop definitions by using several iterations of surveys
      eliciting opinions from specialists in the field. Three consecutive surveys were
      designed based on the Delphi approach and distributed to specialist physicians,
      nurses and physiotherapists in order to develop definitions for seven haemophilia
      terms: 'primary prophylaxis', 'secondary prophylaxis', 'target joint', 'joint
      bleed', 'significant soft-tissue bleed', 'superficial soft-tissue bleed' and
      'mucosal bleed'. Suggestions were solicited, compiled into a subsequent survey
      and fed back to the group to rank-order the importance of each suggested
      component of the definition. Final definitions were created using the top-ranked
      suggestions and sent back to the experts for approval. Five of the seven terms
      were highly endorsed with greater than 90% agreement. Some differences in
      agreement were found when analysed by profession. Haemophilia terms were
      successfully defined using the Delphi approach. Further refinement from members
      of the international haemophilia community will ensure that comprehensive
      standard definitions can be used in multicentre studies in the future.

PMID- 17212720
TI  - Von Willebrand disease within the collective of haemophilic patients as reason
      for unexpected bleeding episodes.
AB  - In the treatment of haemophilia A and B, recombinant coagulation factors are
      increasingly replacing plasma-derived factor VIII and IX concentrates. Although
      provided with replacement therapy, individual patients may exhibit bleeding
      episodes, which are difficult to control. These bleeds may be caused by von
      Willebrand disease (VWD) as an additional underlying coagulation disorder. We
      report in the present study our experience that in the collective of haemophilic
      patients, VWD must be anticipated at least with the same order of magnitude as it
      appears in a normal healthy population. Among the patients at our treatment
      centre, two patients (1.5%) were identified as suffering from VWD in addition to
      haemophilia A. In the collective of haemophilia B patients at our centre, three
      patients (10%) with VWD were found. Two of these patients exhibited unexpected
      severe bleeding episodes, which could only satisfactorily be controlled by the
      administration of Haemate-P or DDAVP supplementary to the recombinant coagulation
      factor concentrate.

PMID- 17212721
TI  - Combined clotting factor deficiencies: experience at a single hemophilia
      treatment center.
AB  - We describe a series of patients with combined factor deficiencies and von
      Willebrand's disease (VWD) at one haemophilia treatment centre. Although the
      incidence of VWD is at least 1% in the general population, combined coagulation
      defects have been infrequently described in the medical literature and are likely
      under diagnosed. This entity should be considered in patients with a known factor
      deficiency and either an unexpectedly severe bleeding phenotype, or bleeding that
      is unresponsive to factor replacement.

PMID- 17212722
TI  - Defining 'full-length' recombinant factor VIII: a comparative structural
      analysis.
AB  - Coagulation factor VIII (FVIII) is an important glycoprotein co-factor involved
      in haemostasis, functioning to accelerate activation of factor X by activated
      factor IX. Insertion of expression vectors containing the full-length cDNA
      sequence of human FVIII into mammalian cell lines results in the production of
      recombinant factor VIII (rFVIII), typically referred to as 'full-length' rFVIII
      (FLrFVIII). Both FLrFVIII and plasma-derived FVIII exist primarily as
      heterodimeric proteins, consisting of a heterogenous light and heavy chain. The
      objectives of this study were to compare the structural heterogeneity of high
      purity FVIII preparations and further define the term 'full length' as it refers
      to rFVIII protein structure. Five commercially available FVIII concentrates were
      characterized based on SDS-PAGE, N-terminal sequencing, and peptide and domain
      mapping coupled to mass spectrometry. The major heavy chain species identified in
      FLrFVIII included various B-domain-truncated forms of FVIII, with the predominant
      species terminating at Arg(1313). This study demonstrates that the use of full
      sequence FVIII cDNA for the production of rFVIII does not result in a homogeneous
      FLrFVIII protein product. Rather, commercially available FLrFVIII represents a
      heterogenous mixture of various B-domain-truncated forms of the molecule, with no
      evidence of a contiguous, intact B-domain.

PMID- 17212723
TI  - Current use of by-passing agents in Europe in the management of acute bleeds in
      patients with haemophilia and inhibitors.
AB  - The ultimate goal of treatment for patients with inhibitory antibodies should be
      to permanently eradicate the inhibitor by immune tolerance induction therapy
      (ITI). However, ITI procedures fail in a substantial number of patients and in
      many countries ITI is not even offered owing to its high cost. How patients with
      inhibitors are managed in different European countries is evaluated with a
      special focus on the use of by-passing agents, i.e. recombinant FVIIa (rFVIIa)
      and activated prothrombin complex concentrates (aPCC), as well as the type of
      monitoring performed. Investigators from 22 large haemophilia centres
      participating within the network of the European Haemophilia Therapy
      Standardisation Board (EHTSB) were asked to complete a questionnaire. rFVIIa was
      routinely used in all centres for both children and adults at dosages ranging
      from 90 to 250 mug kg(-1) at an interval of 2-4 h. aPCC was used in 85% of the
      centres in adults and in 25% of the centres in children with haemophilia A at
      dosages of 50-100 IU kg(-1) every 6-12 h. The corresponding figures for children
      and adults with haemophilia B were 40% and 15% of the centres, respectively.
      Higher dosages of both agents were considered in the case of life-threatening
      bleeds. General recommendations were developed, based on the information provided
      by the survey. The results clearly indicate the need for well-designed
      comparative studies to optimize the use of by-passing agents.

PMID- 17212724
TI  - Rituximab for the treatment of patients with very high-titre acquired factor VIII
      inhibitors refractory to conventional chemotherapy.
AB  - Acquired factor VIII (FVIII) inhibitors are a rare cause of coagulopathy which
      are associated with a high mortality rate. Treatment of bleeding episodes is
      often difficult and may vary with the degree of titre elevation. Individuals with
      very high-titre antibodies [>100 Bethesda units mL(-1) (BU)] may have difficulty
      achieving a complete sustained remission and, consequently, various treatments
      including immunosuppression, cytotoxic chemotherapy and plasmapheresis have been
      reported. Rituximab is an anti-CD20 monoclonal antibody which has demonstrated
      efficacy in the treatment of individuals with acquired FVIII inhibitors, however
      there is limited data in the subgroup of patients with inhibitor titres >100 BU.
      In this study, we present four patients with acquired FVIII inhibitor titres >100
      BU who were resistant to initial therapy with cyclophosphamide, vincristine and
      prednisone. The patients' inhibitor titres ranged from 249 BU mL(-1) to 725 BU
      mL(-1) and all received 4 weekly infusions of rituximab at 375 mg m(-2). Each
      patient partially responded to rituximab therapy with an improvement in inhibitor
      titres and FVIII activity, however, three of the four patients relapsed
      thereafter. The individual who did not relapse achieved a partial response for 13
      months and then died of causes unrelated to her coagulopathy. We conclude that in
      patients with acquired FVIII inhibitors and titres >100 BU, treatment with
      rituximab alone is effective but not sufficient to achieve a sustained response.
      Rituximab in combination with other therapies may provide a better result in this
      high-risk population.

PMID- 17212725
TI  - Impact of different inhibitor reactivities with commercial factor VIII
      concentrates on thrombin generation.
AB  - In order to describe the haemostatic role of a variation in inhibitor reactivity
      with different factor VIII (FVIII) concentrates, we have compared inhibitor
      titres against a panel of FVIII concentrates and correlated titre with the
      capacity to inhibit thrombin generation. Three plasma-derived concentrates were
      tested in vitro in mixing experiments with inhibitor plasmas from 11 patients
      with severe haemophilia A: Fanhdi, which contains von Willebrand factor (VWF)
      with a final ratio of approximately 1:1 (VWF IU per IU FVIII:C); Haemate-P with a
      ratio of 2.5:1 and Hemofil-M containing only trace amounts of VWF. In addition,
      the recombinant FVIII concentrate Kogenate Bayer containing no VWF was included.
      Inhibitor titres and the capacity to generate thrombin were measured. A
      statistically significant difference in measured titres was found with the
      highest titres recorded against Hemofil-M. The inhibitor titres needed to inhibit
      50% maximum thrombin generation were the lowest for Kogenate Bayer and the
      highest and similar for Fanhdi and Haemate-P with intermediate titres needed for
      inhibition of Hemofil-M. In this study, the thrombin generation assay provides
      additional indications for the role of VWF in the treatment of patients with
      inhibitors. The VWF-containing concentrates Fanhdi and Haemate-P, added to FVIII
      deficient plasma with the presence of inhibitor, generate more thrombin than do
      the purified concentrates Hemofil-M and Kogenate Bayer.

PMID- 17212726
TI  - Monitoring the genotoxic effects of radiosynovectomy with Re-186 in paediatric
      age group undergoing therapy for haemophilic synovitis.
AB  - PURPOSE: The aim of this study was to investigate the genotoxic effect on the
      peripheral blood lymphocytes potentially induced by Re-186 in paediatric age
      group undergoing radiosynovectomy for haemophilic synovitis, by using chromosomal
      aberration analysis (CA) and the micronuclei (MN) assay for detecting chromosomal
      aberrations, as well as the sister chromatid exchanges (SCE) technique for
      assessing DNA damage. METHODS: Cytogenetic analyses were evaluated in 20 boys
      (mean age: 13.8 +/- 2.7 years) before, and 2 and 90 days after radiosynovectomy
      from the peripheral lymphocytes of the patients. Joint retention and extra
      articular spread of the radionuclides were evaluated by using quantitative gamma
      camera imaging. RESULTS: Imaging after radiosynovectomy revealed local lymph node
      visualization in 8 (40%) patients and hepatosplenic visualization in 3 (15%)
      patients due to extra-articular leakage of radioactive material. The mean
      frequency of chromosome aberrations (0.2 +/- 0.4/1000 cells) determined prior to
      the onset of therapy was not significantly increased in comparison with control
      values obtained 2 days (0.4 +/- 0.5/1000 cells) and 90 days (0.2 +/- 0.4/1000
      cells) after therapy (P = 0.754 and P = 1.0). In the analysis of MN and SCE, when
      we compare the baseline levels, the mean MN and SCE frequencies were slightly
      higher in the control analyses performed 2 and 90 days after radiosynovectomy but
      there were no significant differences between baseline and control levels (chi(2)
      = 2.621, P = 0.270 and F = 0.573, P = 0.569, respectively). CONCLUSION: The major
      finding of this study with relatively small sample is that, radiosynovectomy with
      Re-186 does not seem to induce early genotoxic effects on the peripheral blood
      lymphocytes in paediatric age group.

PMID- 17212727
TI  - Force fluctuations during the Maximum Isometric Voluntary Contraction of the
      quadriceps femoris in haemophilic patients.
AB  - In the general population, the degenerative processes in joints are directly
      related to adult age, and osteoarthrosis represents the most frequent
      musculoskeletal alteration. In the haemophilic patient, the degenerative
      processes in the joint begin at very early ages, and are directly related to
      musculoskeletal bleeding episodes, which are occasionally subclinical and
      constitute haemophilic arthropathy. In the haemophilic patient, arthropathy
      constitutes the most frequent, severe and disabling pathology, and its assessment
      includes muscular force-related parameters. We have studied the value of Maximum
      Isometric Voluntary Contraction in the quadriceps femoris of 46 subjects, 28
      haemophiliacs (16 severe, eight moderate and four mild) and 18 healthy
      individuals with a view to establishing appropriate values of force and to
      restoring physical therapy recommendations. The maximum force values were
      significantly greater (P < 0.001) in the healthy individuals group. The mild
      haemophiliacs group also presented significant differences of force (P < 0.05) in
      relation to the severe and moderate haemophilic patient groups. The mild and
      severe haemophilia patients presented greater fluctuations of force (P < 0.001)
      than the control group, the haemophilia group have a minor skill to produce
      constant force. The seriousness of the arthropathy in the knee is directly
      related to diminished values of maximum force. Our work evidences that patients
      with severe haemophilia present a greater degree of arthropathy in relation to
      moderate and mild haemophilia patients. Haemophilic arthropathy is associated
      with muscular atrophy and strength deficit. In haemophilic patients, the deficit
      of maximum force and the presence of fluctuations may suggest an increased risk
      of bleeding during physical activities and the need to programme specific
      physical therapy guidelines which increase muscular power through resistance
      training.

PMID- 17212728
TI  - The Colorado Haemophilia Paediatric Joint Physical Examination Scale: normal
      values and interrater reliability.
AB  - Persons with haemophilia often experience their first joint haemorrhage in early
      childhood. Recurrent bleeding into a joint may lead to significant morbidity,
      specifically haemophilic arthropathy. Early identification of the onset and
      progression of joint damage is critical to preserving joint structure and
      function. Physical examination is the most feasible approach to monitor joint
      health. Our group developed the Colorado Haemophilia Paediatric Joint Physical
      Examination Scale to identify earlier signs of joint degeneration and incorporate
      developmentally appropriate tasks for assessing joint function in young children.
      This study's objectives were to establish normal ranges for this scale and assess
      interrater reliability. The ankles, knees and elbows of 72 healthy boys aged 1
      through 7 years were evaluated by a physical therapist to establish normal
      ranges. Exactly 10 boys in each age category from 2 to 7 years were evaluated by
      a second physical therapist to determine interrater reliability. The original
      scale was modified to account for the finding that mild angulation in the weight
      bearing joints is developmentally normal. The interrater reliability of the scale
      ranged from fair to good, underscoring the need for physical therapists to have
      specific training in the orthopaedic assessment of very young children and the
      measurement error inherent in the goniometer. Modifications to axial alignment
      scoring will allow the scale to distinguish healthy joints from those suffering
      frequent haemarthroses.

PMID- 17212729
TI  - Osteoporosis in haemophilia - an underestimated comorbidity?
AB  - A relationship between haemophilia and osteoporosis has been suggested, leading
      to the initiative for a larger study assessing this issue. Bone mineral density
      (BMD) was measured by osteodensitometry using dual energy X-ray absorptiometry
      (DEXA) in 62 male patients with severe haemophilia A; mean age 41 +/- 13.1 years,
      mean body mass index (BMI) 23.5 +/- 3.6 kg m(-2). Using the clinical score
      suggested by the World Federation of Hemophilia, all patients were assessed to
      determine the severity of their arthropathy. A reduced BMD defined as osteopenia
      and osteoporosis by World Health Organization criteria was detected in 27/62
      (43.5%) and 16/62 (25.8%) patients, respectively. Fifty-five of sixty-two (88.7%)
      patients suffered from haemophilic arthropathy. An increased number of affected
      joints and/or an increased severity were associated with lower BMD in the neck of
      femur. Pronounced muscle atrophy and loss of joint movement were also associated
      with low BMD. Furthermore, hepatitis C, low BMI and age were found to be
      additional risk factors for reduced BMD in the haemophiliac. Our data shows that
      in haemophilic patients osteoporosis represents a frequent concomitant
      observation. The main cause for reduced bone mass in the haemophiliac is most
      probably the haemophilic arthropathy being typically associated with chronic pain
      and loss of joint function subsequently leading to inactivity. Further studies
      including control groups are necessary to elucidate the impact of comorbidities
      such as hepatitis C or HIV on the development of osteoporosis in the
      haemophiliac.

PMID- 17212730
TI  - Short-term oral corticosteroid therapy for acute haemarthrosis in haemophilia
      patients with high-titre inhibitors.
AB  - Treatment of acute bleeding events is unsatisfactory in patients with haemophilia
      and high-titre factor VIII (FVIII) inhibitors. In order to determine whether
      short-term corticosteroid therapy enhances resolution of the signs and symptoms
      of acute haemarthrosis, we performed a randomized, double-blind, placebo
      controlled study in children with FVIII deficiency and high-titre inhibitors
      receiving Factor Eight Inhibitor Bypass Activity (FEIBA) for acute haemorrhagic
      events. At each haemarthrosis, patients were randomized to receive either
      prednisolone 2 mg kg(-1) day(-1) or placebo-divided t.i.d. for 2 days (six doses)
      in addition to FEIBA. The primary endpoint was the number of subsequent doses of
      FEIBA required. The effect of the study medication was also assessed subjectively
      by patients or parents, by physical examination and by repeated haemorrhages into
      the joint. During the study period, seven patients were enrolled with 45
      evaluable events, 24 treated with prednisolone and 21 with placebo. An average of
      2.08 and 1.86 doses of FEIBA were infused in the prednisolone- and placebo
      treated patients, respectively. By Wilcoxon Rank Sum Test, there was no
      statistically significant difference in number of additional infusions of FEIBA
      or duration of symptoms between the corticosteroid and placebo arms. We conclude
      that there is no significant benefit of a 2-day course of oral corticosteroids as
      adjunctive therapy for haemarthrosis in patients with haemophilia and a high
      titre inhibitor.

PMID- 17212731
TI  - Prevalence of sporadic and familial haemophilia.
AB  - In an analysis of 804 haemophilia pedigrees, mild to moderate haemophilia A or B
      was found to be clearly familial in 70% of cases, severe haemophilia B in 57% of
      cases and severe haemophilia A in 45% of cases. The rest of the patients were
      'sporadic' i.e., either isolated cases or brothers in the first affected sibship.
      In sporadic families, 88% of mothers but only 19% of maternal grandmothers had
      the relevant mutation in their white blood cells. Among patients with familial
      haemophilia, half the patients with mild haemophilia and those with severe
      haemophilia B had a direct male ancestor with haemophilia, but only 28% of
      patients with severe haemophilia A had such a progenitor.

PMID- 17212732
TI  - Haemoperitoneum associated with ovulation in women with bleeding disorders: the
      case for conservative management and the role of the contraceptive pill.
AB  - Haemoperitoneum secondary to ruptured corpus luteum is a rare complication for
      women on anticoagulants and with certain congenital bleeding disorders. A
      surgical approach is often taken, leading to oophorectomy in many cases. We
      describe three patients presenting with haemoperitoneum in association with
      factor VII deficiency, factor X deficiency and sitosterolaemia. In two of the
      patients, recurrent episodes occurred prior to introduction of the oral
      contraceptive pill. Conservative management with blood product and factor
      concentrate support was successful in avoiding surgery in three of the five
      episodes of bleeding. These cases demonstrate that preservation of ovarian
      function is possible with a conservative approach and recurrent episodes may be
      prevented by suppression of ovulation.

PMID- 17212733
TI  - Pegylated interferon and ribavirin combination therapy for chronic hepatitis C in
      patients with congenital bleeding disorders: a single-centre experience.
AB  - Chronic hepatitis C is a major comorbidity in patients with haemophilia. Although
      the current state-of-the-art therapy consists of pegylated interferon (PegIFN)
      and ribavirin, there are no reports of the efficacy of this combination in the
      haemophilia population. The aim of this study was to assess the response and side
      effects of PegIFN and ribavirin in patients with inherited bleeding disorders.
      Patients with chronic hepatitis C were treated with PegIFN alpha-2b (1.5 microg
      kg(-1) week(-1)) and ribavirin (800-1200 mg day(-1)) for 24 (genotype 2 and 3) or
      48 weeks (genotype 1) and followed for an additional 24 weeks. In total, 56
      patients were enrolled: 31 (55%) had genotype 1, 12 (21%) genotype 2, and 13
      (23%) genotype 3. Ten patients (18%) were HIV co-infected and seven (13%) had
      been previously treated with IFN-alpha with or without ribavirin. The overall
      response was 55%. In HIV-negative and treatment-naive patients, the sustained
      virological response was 70%. Successful treatment was associated with genotypes
      2 and 3, absence of HIV, absence of previous IFN treatment, and decrease of
      hepatitis C virus load at weeks 4 and 12. Although many side-effects occurred,
      only a minority (11%) discontinued therapy for this reason. Dose reduction of
      PegIFN was required in 28% and of ribavirin in 35% of patients. Overall, 22% of
      patients developed a depression requiring antidepressant drugs and one patient
      developed psychosis. In conclusion, PegIFN and ribavirin is effective in patients
      with inherited bleeding disorders. Treatment is safe, but severe side-effects may
      occur and warrant close monitoring during therapy.

PMID- 17212734
TI  - IgE-mediated anaphylactic reaction to purified and recombinant factor VIII in a
      patient with severe haemophilia A.
AB  - We report a 51-year-old patient with severe haemophilia A developing a severe
      life-threatening anaphylactic reaction to recombinant factor VIII (rFVIII).
      Anaphylactic reactions are a rare but well-known side effect of FVIII products.
      The nature of these reactions could not be clarified as previous studies failed
      to demonstrate a specific IgE response. Here, we could prove a grade 3
      anaphlyactic reaction as an IgE-mediated response to rFVIII for the first time by
      Western blotting.

PMID- 17212735
TI  - Combined factor VIII and IX inhibitors in a non-haemophilic patient: successful
      treatment with immunosuppressive drugs.
AB  - A rare case of a patient with Sjogren syndrome and spontaneously acquired
      inhibitors of both factor VIII and factor IX is reported. Complete remission was
      obtained by means of immunosuppressive drugs.

PMID- 17212736
TI  - Rituximab as an adjuvant therapy to immune tolerance in a haemophilia A boy with
      high inhibitor titre.
AB  - We report a haemophilia A boy with high inhibitor titre (170 BU) who experienced
      five life-threatening bleeding episodes during a one-year period from 9 to 21
      months. At the age of 22 months, he received rituximab (375 mg m(-2) per dose) at
      one- and three-week intervals, three courses each and alternative daily treatment
      with factor VIII concentrate at doses of 100 units kg(-1) for 24 weeks and 50
      units kg(-1) for the following 28 weeks. Although the pretreatment inhibitor
      level of 4.5 BU showed an anamnestic response reaching the maximum level of 200
      BU at the 9th week of treatment, it gradually declined to 30 BU at the 22nd week
      and was constantly maintained at 25-30 BU for the following 30 weeks. Only three
      bleeding episodes of two haematomas and one haemarthrosis were found during the
      one-year treatment period. No opportunistic infection occured during this period.

PMID- 17212737
TI  - Cyclosporin A can achieve immune tolerance in a patient with severe haemophilia B
      and refractory inhibitors.
AB  - Immune tolerance induction (ITI) is described in a patient with severe
      haemophilia B complicated by the presence of an inhibitor. A number of ITI
      regimes were attempted without success and the patient suffered from frequent
      relapses and bleeding episodes. Successful ITI was achieved with the additional
      use of cyclosporin A. The patient developed nephrotic syndrome although had a
      negative Bethesda titre at this time. When cyclosporin A therapy was ceased, the
      inhibitor titre rose and the patient suffered again from bleeding episodes.
      Cyclosporin A was reintroduced at a lower dose. The patient has now received
      cyclosporin A for 10 years, during which time he has relapsed three times for
      short periods (2 weeks). He is also on prophylaxis with factor IX three times a
      week with preinfusion levels >1% and without bleeding.

PMID- 17212738
TI  - Topical use of tranexamic acid to control perioperative local bleeding in
      gynaecology patients with clotting disorders: two cases.
AB  - Operating on patients with abnormal coagulation is a challenge frequently faced
      by surgeons. Achieving haemostasis perioperatively can involve bleeding points
      that would not ordinarily present a problem with intact clotting function. Here
      we present two women with localised wound bleeding following a gynaecological
      surgery in the presence of a clotting disorder. Haemostasis was successfully
      achieved with tropical use of tranexamic acid. These two cases illustrate a novel
      use for this antifibrinolytic agent. We suggest that there is a role for topical
      use of tranexamic acid in perioperative haemostasis in patients with clotting
      disorders.

PMID- 17212740
TI  - Stayin' alive.

PMID- 17212739
TI  - Confusion around the official classification of arthropathy.

PMID- 17212742
TI  - Results of pacemaker implantation in 104 dogs.
AB  - OBJECTIVES: To document the outcome, survival and complications involved in
      pacemaker implantation in dogs in a retrospective study. METHODS: Case records
      for all dogs in which pacemaker implantation was performed were reviewed.
      RESULTS: A total of 104 dogs underwent pacemaker implantation. Dogs were
      presented with atrioventricular (AV) block (71), sick sinus syndrome (25) or
      vasovagal syncope (eight). Age at presentation varied from six months to 13 years
      with a median age of seven years and two months. The Labrador was the most
      commonly represented breed (17 cases). All but one dog survived pacemaker
      implantation, with 93 showing resolution of their clinical signs while 10 dogs
      showed intermittent residual signs. One-, three- and five-year survival estimates
      were 86, 65 and 39 per cent, respectively. Major complications after implantation
      were documented in 15 dogs and three of these led to fatalities. Minor
      complications were noted in 23 dogs. Sudden death occurred in six dogs three to
      55 months following successful pacemaker implantation. CLINICAL SIGNIFICANCE:
      Transvenous pacemaker implantation was successful in reducing or eliminating
      clinical signs in over 90 per cent of dogs with third-degree atrioventricular
      (AV) block or sick sinus syndrome. In dogs with vasovagal syncope, six of eight
      dogs had greatly reduced frequency of collapse and two became asymptomatic.
      Although the procedure was associated with complications, these were rarely life
      threatening and good survival was documented in the majority of cases.

PMID- 17212743
TI  - Successful medical treatment of 15 dogs with pyothorax.
AB  - OBJECTIVES: To review the success of non-surgical management, which included
      antibiotics and a single thoracocentesis, in 15 dogs presenting with pyothorax.
      METHODS: Sixteen dogs were selected retrospectively from case files at the
      Veterinary Cardiorespiratory Centre. RESULTS: One dog was diagnosed with a mass
      suspected to be a pulmonary abscess on ultrasound examination and was referred
      for surgery. Fifteen dogs were treated medically. Springer spaniels were the most
      commonly presented breed (six cases) followed by Labrador retrievers (three
      cases). Under sedation or general anaesthesia, thoracocentesis was performed
      unilaterally and as much purulent effusion as possible was removed. Lavage of the
      thorax was not undertaken. In most dogs, antibiotic treatment was ampicillin at a
      mean dose of 33 mg/kg administered three times daily and 25 mg/kg metronidazole
      administered twice daily. Antibiotics were provided for a minimum of six weeks.
      All dogs recovered completely and did not show relapse on prolonged follow-up.
      This included one dog, which had very widespread pleural adhesions and minimal
      effusion. CLINICAL SIGNIFICANCE: In dogs that do not have evidence of pulmonary
      masses or consolidations and no evidence of granular pleural effusion, medical
      therapy may be curative even in chronic cases of pyothorax with pleural
      adhesions.

PMID- 17212744
TI  - Evaluation of transanal endoscopic treatment of benign canine rectal neoplasia.
AB  - OBJECTIVES: To evaluate transanal endoscopic treatment in the management of
      benign canine rectal neoplasia. METHODS: A retrospective study was carried out to
      evaluate the response to transanal endoscopic treatment in 13 dogs with extensive
      rectal neoplasia that was considered inoperable by conventional surgical
      techniques but was indicated as benign by previous biopsy. RESULTS: Tumours
      affected the lengths of rectal mucosa varying from 2 to 13 cm. Between 25 and 100
      per cent of the rectal circumference was affected in each case. Transanal
      endoscopic treatment of canine rectal neoplasia was curative in five dogs,
      palliative in three and associated with a poor result in the remaining five.
      Complications of the technique included rectal perforation, leading to
      peritonitis and death. CLINICAL SIGNIFICANCE: Transanal endoscopic treatment can
      be recommended as an alternative to radical, full-thickness rectal excision for
      the management of extensive but benign canine rectal neoplasia. Owners should be
      informed that the treatment may be palliative rather than curative and that
      complications, if they occur, can be fatal. Dogs should be hospitalised for at
      least five days after treatment and observed for signs of potentially fatal
      complications such as rectal perforation.

PMID- 17212745
TI  - Perceptions of veterinarians and clients to expressions of clinical uncertainty.
AB  - OBJECTIVES: The aim of this study was to explore the attitudes of veterinarians
      and clients towards expressions of clinical uncertainty. METHODS: Questionnaires
      that assessed the respondent's attitudes towards expressions of clinical
      uncertainty were completed by clients at six small animal practices. In addition,
      questionnaires that evaluated what veterinarians thought their client's attitudes
      would be towards expressions of clinical uncertainty were completed by
      veterinarians. The responses from clients and veterinarians were statistically
      compared. RESULTS: Veterinarians significantly underestimated the desire of
      clients to be told about uncertainties in treatment and significantly
      overestimated how the expression of uncertainty would generally reduce client
      confidence. Veterinarians significantly overestimated the loss of client
      confidence resulting from saying "I am not sure about this" and from asking a
      nurse for advice. Both clients and veterinarians considered that verbal
      expressions of uncertainty would lead to a greater reduction in client confidence
      than behavioural expressions of uncertainty. CLINICAL SIGNIFICANCE: This study
      suggests that most clients want to be told about their veterinarian's clinical
      uncertainties, and how this uncertainty is expressed can markedly influence
      client confidence.

PMID- 17212746
TI  - Multiple vascular anomalies in a regurgitating German shepherd puppy.
AB  - Five cardio-thoracic vascular anomalies were detected in a German shepherd puppy.
      The patent ductus arteriosus (PDA) was detected on physical examination (5/6
      continuous murmur) and confirmed by echocardiogram. The persistent right aortic
      arch (PRAA) was suspected by the signalment and history of the patient, and
      confirmed by survey thoracic radiographs (leftward deviation of the trachea
      cranial to the heart on the ventrodorsal projection). The ventrally deviated
      trachea cranial to the heart on the right lateral thoracic radiograph was
      suggestive of a persistent retroesophageal left subclavian artery and confirmed
      at surgery. The persistent left cranial vena cava and the left azygous vein were
      detected at surgery. This case report gives a thorough description of the
      clinical signs, diagnostics and treatments required for the detection and
      successful resolution of PRAA. The report describes the importance of having
      experienced surgeons who can recognize vascular anomalies associated with PRAA in
      order to successfully alleviate the arch and the coinciding oesophageal stricture
      without compromising vital blood supplies.

PMID- 17212747
TI  - X-linked spondylo-epiphyseal dysplasia tarda in the Danish-Swedish farm hound.
AB  - In two litters from the same parents, three out of four males had an abnormally
      short leg and body length. Affected dogs showed signs of pain when moving, which
      could be eliminated by analgesia. On radiography, these animals had widened,
      radiolucent, irregularly bordered intervertebral disc spaces. When examined at
      seven months of age, the epiphyses appeared widened and irregular in shape and
      outline. General bone opacity in the vertebral column was lower in the affected
      male dogs than in the normal littermate. The affected dogs developed spondylosis
      and arthrosis of the larger limb joints. All affected dogs were euthanased on
      humane grounds, the eldest at the age of two years nine months. Based on the
      clinical and radiographic evidence, the condition seen in the male dogs described
      here resembles X-linked spondylo-epiphyseal dysplasia tarda caused by a
      collagenopathy due to malformation of COL2A1 as seen in human beings.

PMID- 17212748
TI  - Partial tarsal arthrodesis and botulinum toxin A injection for correction of
      tarsal arthrogryposis in a cat.
AB  - An 11-week-old, domestic shorthair cat was presented for evaluation of a
      congenital right tarsal deformity. The cat was non-weightbearing lame on the
      right hindlimb. There was severe tarsal hyperextension and concurrent
      spasticity/contracture/shortening of the gastrocnemius muscle-tendon. The cat was
      otherwise healthy. Radiographically there was luxation of the proximal
      intertarsal joint and talocrural hyperextension. Treatment with 10 mu/kg
      botulinum toxin A (Botox; Allergan) intramuscular injections directly into the
      gastrocnemius muscle and passive physiotherapy marginally improved the range of
      motion in the talocrural joint. Definitive surgical treatment with partial tarsal
      arthodesis produced an excellent clinical outcome. This case report demonstrates
      the successful treatment of a severe congenital tarsal abnormality and also
      documents the first clinical use of botulinum toxin in a feline patient.

PMID- 17212749
TI  - Perirenal expanding haematoma in a cat.
AB  - A four-year-old, entire male domestic cat was referred for assessment of a large
      abdominal mass of three-weeks duration. Diagnostic imaging suggested the presence
      of either splenic neoplasia, an abdominal abscess or haematoma. A coeliotomy was
      performed and an enlarged, irregular mass, including the left kidney and adrenal
      gland, was identified. The mass was removed, requiring a left adrenalo-uretero
      nephrectomy. The aorta was accidentally punctured during the procedure, resulting
      in paraplegia. Given a poor prognosis, the owners decided to have the cat
      euthanased. Histological examination of the mass was characteristic of a chronic
      expanding haematoma.

PMID- 17212751
TI  - Pontine infarction in a dog with unilateral involvement of the trigeminal motor
      nucleus and pyramidal tract.
AB  - An unusual case of unilateral trigeminal neuronopathy in a dog is reported, in
      which the motor nucleus of the trigeminal nerve and the ipsilateral corticospinal
      tract were destroyed, apparently by a cerebrovascular accident (stroke).
      Hemiplegia did not occur. Neuropathological changes are described, including
      remyelination by Schwann cells in the central nervous system. The case
      illustrates the importance of central nervous system post-mortem examination when
      establishing causes of cranial nerve paralysis.

PMID- 17212750
TI  - Liposuction--removal of giant lipomas for weight loss in a dog with severe hip
      osteoarthritis.
AB  - An extremely obese, mixed breed dog, with severe bilateral hip osteoarthritis was
      presented with progressive hindlimb lameness. In addition, three giant lipomas
      were diagnosed, one causing mechanical irritation within the left axillary
      region. Previous treatments of dietary weight loss and non-steroidal anti
      inflammatory drugs had failed. Minimally invasive liposuction of the lipomas was
      performed, resulting in weight loss of 3 kg, representing 10 per cent of the
      dog's bodyweight. Conservative treatment was continued, and the dog improved
      rapidly postoperatively. Liposuction of lipomas may be considered as an
      alternative to traditional surgical resection in cases where seroma formation and
      delayed wound healing may be expected. Acute weight loss through liposuction may
      improve lameness associated with osteoarthritis and motivate the owner compliance
      for further weight loss.

PMID- 17212752
TI  - What is your diagnosis? Ovarian teratoma.

PMID- 17212753
TI  - Creating a successful school-based mobile dental program.
AB  - BACKGROUND: Dental disease is one of the leading causes of school absenteeism for
      children. This article describes the creation and evolution of the St. David's
      Dental Program, a mobile school-based dental program for children. METHODS: The
      dental program is a collaboration of community partners in Central Texas that
      provides free dental care to low-income children in schools without relying on
      reimbursements or government funding. RESULTS: Since 1998, the program has
      provided 132,791 screenings for oral health treatment needs and 38,634 encounters
      for sealants or treatment. In 2005, the program provided $2.1 million worth of
      services at a cost of $1.2 million (not including donated services). Factors
      important to the program's success included sustained funding for general
      operating costs; well-compensated clinicians to deliver care and experienced
      human service workers to manage program operations; the devotion of resources to
      maximize consent form return rates; and the development of strong relationships
      with school district and individual school staff. CONCLUSIONS: By removing cost,
      time, transportation, and bureaucratic barriers, the program was able to reach
      more children than fixed-site clinics. The program was a merging of private and
      public health dentistries. This model can be useful to other communities in light
      of the unmet need for dental care and tighter federal, state, and local
      government budgets.

PMID- 17212754
TI  - Early adolescents perceptions of health and health literacy.
AB  - BACKGROUND: Health illiteracy is a societal issue that, if addressed
      successfully, may help to reduce health disparities. It has been associated with
      increased rates of hospital admission, health care expenditures, and poor health
      outcomes. Because of this, much of the research in the United States has focused
      on adults in the health care system. This study investigated the effect of
      aspects of health literacy on the motivation to practice health-enhancing
      behaviors among early adolescents. METHODS: Measures were generally based on 3
      National Health Education Standards for grades 5-8. Data were obtained from 1178
      9- to 13-year-old students visiting 11 health education centers in 7 states.
      Students responded via individual electronic keypads. RESULTS: Multivariate
      logistic regression revealed that, in addition to age, difficulty understanding
      health information and belief that kids can do little to affect their future
      health, decreased the likelihood for interest in and desire to follow what they
      were taught about health. Further, low interest independently decreased
      motivation to follow what was taught. Girls were more likely to turn to school,
      parents, and medical personnel for health information. Older students were more
      likely to turn to school and to the Internet. CONCLUSIONS: Programs and curricula
      should be designed to increase student interest in health issues and their self
      efficacy in controlling their own health destinies. Educators should also teach
      students to more effectively use nonconventional health information sources such
      as the Internet, parents, and medical professionals.

PMID- 17212755
TI  - Not just pushing and shoving: school bullying among African American adolescents.
AB  - BACKGROUND: The primary purpose of this study was to examine the prevalence of
      bullying among a sample of African American adolescents and the risk factors
      associated with odds that a student engages in bullying behavior. METHODS: Using
      a self-report school-based survey, 1542 African American adolescents from a
      single school district (grades 5-12) living in a midsized, Southern metropolitan
      region, were asked questions regarding bullying behavior and risk behaviors. A
      response rate of nearly 80% was obtained. RESULTS: Our results indicate that
      bullying behavior was higher among this group of African American adolescents
      than reported for other general student populations (8-12%). In addition, age,
      family violence, negative peer relationships, and behavioral risks all
      contributed to increased odds of students reporting bullying behavior.
      CONCLUSIONS: Our findings underscore the importance of intervention at an early
      age. Whether the intervention is in a formal or nonformal setting, specialists
      along with teachers, parents, and siblings need to begin a multipronged approach
      (data collection, training/education of school personnel, curriculum development,
      etc) to address the causes and consequences of bullying among adolescents.

PMID- 17212756
TI  - Comparing data collected by computerized and written surveys for adolescence
      health research.
AB  - BACKGROUND: This study assessed whether data-collection formats, computerized
      versus paper-and-pencil, affect response patterns and descriptive statistics for
      adolescent health assessment surveys. Youth were assessed as part of a health
      risk reduction program. METHODS: Baseline data from 1131 youth were analyzed.
      Participants completed the questionnaire either by computer (n = 390) or by paper
      and-pencil (n = 741). RESULTS: The rate of returned surveys meeting inclusion
      requirements was 90.6% and did not differ by methods. However, the computerized
      method resulted in significantly less incompleteness but more identical
      responses. Multiple regression indicated that the survey methods did not
      contribute to problematic responses. The two survey methods yielded similar scale
      internal reliability and descriptive statistics for behavioral and psychological
      outcomes, although the computerized method elicited higher reports of some risk
      items such as carrying a knife, beating up a person, selling drugs, and
      delivering drugs. CONCLUSIONS: Overall, the survey method did not produce a
      significant difference in outcomes. This provides support for program personnel
      selecting survey methods based on study goals with confidence that the method of
      administration will not have a significant impact on the outcome.

PMID- 17212757
TI  - Who's skipping school: characteristics of truants in 8th and 10th grade.
AB  - BACKGROUND: Truancy is a serious concern that affects most school districts in
      the United States; however, we do not have accurate estimates of the prevalence
      of truancy due to inconsistent tracking and reporting practices of schools. As a
      result, our best current estimates of the national state of truancy may be from
      self-reported data. In this article, the first objective is to present the
      prevalence of self-reported recent truancy (ie, truancy within the past 4 weeks)
      among 8th- and 10th-grade students. The second objective is to explore
      associations between recent truant behavior, demographic and family
      characteristics, school-related risk factors, and drug use. METHODS: The 2003
      wave of the Monitoring the Future data was analyzed. Logistic regression analysis
      was used to assess the association between many potential predictors and the
      probability of recent truancy. RESULTS: Nearly, 11% of 8th graders and over 16%
      of 10th graders reported recent truancy. Among the most salient predictors of
      recent truancy were parental education, having large amounts of unsupervised time
      after school, school disengagement variables (eg, poor grades and low educational
      aspirations), and drug use. CONCLUSIONS: Truancy is a common behavior among
      adolescents and can have potentially deleterious effects. This paper offers
      insight into the types of students who may be prone to skipping school and
      suggests potential target audiences for truancy prevention initiatives.

PMID- 17212758
TI  - Fractures in New Zealand elementary school settings.
AB  - BACKGROUND: There is a need for greater international understanding of student
      safety in schools. This New Zealand study investigated the causes and school
      location of fractures sustained by students attending elementary school, with
      special emphasis on the types of fractures sustained following falls from
      playground equipment of various heights. METHODS: Over a 1-year period, 76
      participating schools (with a combined roll of over 25,000 students) completed a
      questionnaire about the nature and circumstances of student fractures sustained
      during regular school hours. RESULTS: Some 118 students sustained a total of 131
      fractures. Injuries from playground equipment were no more frequent than those
      from general activities at school, and most were sustained in falls from heights
      less than 59 inches. Most fractures were to the upper limbs. Fractures were found
      to vary by gender and school size. CONCLUSIONS: The results are discussed in
      terms of the conditions and policies present in local schools, and the tension
      that exists in maintaining safety while offering appropriate challenges to
      students. Improvements in school safety may be more likely to result from a
      greater focus on the way that students interact at school, rather than on
      modifications to playground equipment.

PMID- 17212760
TI  - Differential capacities of outer membrane proteins from Neisseria meningitidis B
      to prime the murine immune system after vaccination.
AB  - Understanding the specificity of antibody response to Neisseria meningitidis
      serogroup B (Men B) is a key requirement for the development of an effective
      vaccine. This study was designed to investigate the antigen specificity of murine
      IgG1 and IgG2b antibodies induced by different primary immunization schedules and
      the booster dose with the Cuban Men B vaccine. Immunoblotting analyses were
      performed using outer membrane vesicles (OMV) from the vaccine strain
      (B:4,7:P1.19,15). IgG subclasses binding to PorA, PorB and RmpM were determined
      by digital scanning of the immunoreactive bands. Bactericidal antibody response
      after vaccination was also evaluated. The results indicated that IgG2b anti-PorA
      was the main antibody response induced by two doses of the vaccine. A primary
      series of three doses was found important for increasing IgG2b as well as IgG1 to
      PorB and RmpM. The fourth dose favoured the recognition of RmpM as detected by
      the increase of specific IgG1 and IgG2b. IgG subclasses anti-PorA did not change
      significantly if animals received two, three or four doses of the vaccine during
      the primary immunization or after the booster dose for all vaccine groups. The
      booster response to PorB and RmpM of groups BC2 and BC3 showed a significant
      increase in IgG2b levels compared with the primary response. However, the recall
      and the primary response of group BC4 were similar, suggesting a saturated dose
      effect response after four doses of vaccine. The same was seen for bactericidal
      antibody response when human complement source was used in the assay.

PMID- 17212759
TI  - Policies and opportunities for physical activity in middle school environments.
AB  - BACKGROUND: This study examined physical activity opportunities and barriers at
      36 geographically diverse middle schools participating in the Trial of Activity
      for Adolescent Girls. METHODS: Principals, physical education and health
      education department heads, and program leaders were interviewed to assess
      policies and instructional practices that support physical activity. RESULTS:
      Schools provided approximately 110 hours per year in physical education
      instruction. Approximately 20% of students walked or bicycled to school. Eighty
      three percent of schools offered interscholastic sports and 69% offered
      intramural sports. Most schools offered programs for girls, but on average, only
      24 girls ( approximately 5%) in the schools attended any programs. Only 25% of
      schools allowed after school free play. An overall score created to assess school
      environmental support for physical activity indicated that, on average, schools
      met 6.7 items of 10 items. Free/reduced lunch program participation versus not (p
      = .04), perceived priority of physical education instruction over coaching (p =
      .02), and safety for walking/bicycling to school (p = .02) predicted
      environmental support score. CONCLUSIONS: Schools have policies and practices
      that support physical activity, although unfavorable practices exist. Schools
      must work with community partners and officials to provide environments that
      optimally support physical activity, especially schools that serve low-income
      students.

PMID- 17212761
TI  - Murine dendritic cells modified with CXCL10 gene and tumour cell lysate mediate
      potent antitumour immune responses in mice.
AB  - The aim of our present study was to estimate the effect of a therapeutic vaccine
      against tumour based on dendritic cells (DC) vaccine modified with tumour cell
      lysate and chemokine CXCL10 gene. In this study, mouse bone marrow DC were pulsed
      with tumour cell (RM-1) lysate and then transfected with a plasmid vector
      expressing CXCL10 cDNA by DOTAP liposome. The protective and therapeutic effects
      of the DC vaccine in RM-1 tumour model were assessed (divided into CXCL10/Lysate
      DC, CXCL10/DC, pcDNA/Lysate-DC, Lysate-DC, pcDNA-DC, DC and PBS). The DC
      transfected with CXCL10 gene were capable of synthesizing and secreting CXCL10
      chemokine. The highest CTL activity against RM-1 cells was induced in mice
      immunized with DC vaccine that was modified with RM-1 lysate and CXCL10 gene
      (CXCL10/Lysate-DC) when compared with its counterpart in mice. The CXCL10/Lysate
      DC immunized mice also exhibited resistance to tumour challenge most effectively.
      In the RM-1 tumour model, immunization of CXCL10/Lysate-DC inhibited the tumour
      growth most significantly when compared with other groups and the survival time
      of the mice treated with CXCL10/Lysate-DC was greatly extended. These findings
      provide a potential strategy to improve the efficacy of DC-based tumour vaccine.

PMID- 17212762
TI  - A comparison of the humoral and cellular immune responses at different
      immunological sites after split influenza virus vaccination of mice.
AB  - The spleen, bone marrow and lymph nodes are all known to be important organs for
      the initiation and maintenance of an immune response after vaccination. To
      investigate the differences and similarities in the humoral and cellular immune
      responses between these tissues, we vaccinated mice once or twice with the
      conventional human dose (15 microg HA) of influenza A (H3N2) split virus vaccine
      and analysed the sera and lymphocytes collected from the different sites. We
      found that the response of antibody secreting cells (ASC) in the lymph nodes
      appeared to be more transient than in the spleen, possibly because the influenza
      specific IgM ASC in particular might have migrated from the lymph nodes
      immediately after activation. The serum antibody response was found to initially
      correspond with the ASC response elicited in the spleen and the lymph nodes,
      whereas the later serum IgG reflected the ASC response in the bone marrow.
      Proliferation of influenza-specific CD4(+) and CD8(+) cells was predominantly
      observed in the spleen and was associated with higher concentrations of cytokines
      than in the lymph nodes. The finding of influenza-specific CD8(+) cell
      proliferation in the spleen indicates that a split influenza virus vaccine may
      stimulate a cytotoxic T-cell response. Our results also showed that the primary
      response elicited a mixed Th1/Th2 profile, whereas the secondary response was
      skewed towards a Th2 type. Each of the three tissues had a different
      immunological pattern, suggesting that in preclinical vaccine studies, there is a
      case for investigating a range of immunological sites.

PMID- 17212763
TI  - Diabetes induces rapid suppression of adaptive immunity followed by homeostatic T
      cell proliferation.
AB  - Surprisingly, the effect of acute diabetes on immunity has not been examined in
      detail. We, herein, show for the first time that untreated acute diabetes causes
      rapid lymphopenia followed by homeostatic T-cell proliferation. The diabetes
      induced lymphopenia was associated with an immunosuppressed state that could be
      sufficiently strong to allow engraftment of fully allogeneic beta-cells or block
      rejection of islet transplants. In contrast, homeostatic proliferation and
      recovery of T-cell numbers were associated with islet rejection. Thus, the timing
      of islet transplant challenge in relation to diabetes induction was critical in
      determining whether islets were accepted or rejected. In addition, we tested
      whether diabetes-related immunosuppression could result in an overestimation of
      the efficacy of a tolerance-inducing protocol. Consistent with this possibility,
      a protocol targeting CD40L and ICOS that we have shown induces tolerance in
      diabetic recipients was unable to induce tolerance in non-diabetic recipients.
      The data uncover a previously unrecognized suppressive effect of diabetes on
      adaptive immunity. Furthermore, they suggest that the standard methods of testing
      new tolerance-inducing protocols in islet transplantation require modification
      and that diabetes itself can contribute to homeostatic proliferation, a process
      associated with autoimmunity and a resistance to tolerance induction.

PMID- 17212764
TI  - Structural evidence for a new IgG1 antibody sequence allele of cattle.
AB  - Analysis of the heavy-chain gene (pTGHC9907) encoding a bovine IgG1 antibody
      against bovine herpes virus type 1 (BHV-1) isolated from a Holstein cow has led
      to the identification of a new IgG1 sequence allele. A comparison of nucleotide
      sequence of pTGHC9907 with the IgG1(a) (clone 2) and IgG1(b) (clone 8.10)
      sequence variants and unclassified IgG1 cDNA sequence (clone 8.75) has revealed
      significant differences in the hinge region spanning codons 216-230. The Thr224
      and Thr226 of IgG1(a) were replaced with Arg224 and Pro226, while both Thr218 and
      Pro224 of IgG1(b) were substituted with Arg with deletion of Ser225 in HB9907
      antibody. Additional amino acid substitutions were noted in the CH1 (positions
      190, 192), CH2 (position 281) and CH3 (position 402) exons. Thus, the polymorphic
      sites occurred in all constant domains, but were clustered in the hinge region of
      IgG1. Examination of a three-dimensional model of the HB9907 heavy chain revealed
      that all sequence variations were on the surface of the IgG and are possible
      targets for recognition by antisera and effector molecules such as cellular
      adhesion molecules. The presence in the CH1 domain of a repeating motif of Pro
      Ala-Ser-Ser indicated a potential structure-enhancing function and a role in
      cellular adhesion and migration. Replacement of Thr with Arg residues within the
      hinge was predicted to have a dual effect of reducing the number of O-linked
      glycosylation sites and increasing the susceptibility to degradation by protease
      secreting bacteria of the hinge region. As unclassified IgG1 cDNA sequence (clone
      8.75) is structurally distinct from other variants, it is also classified as
      IgG1(d). Collectively, these observations support the identification of a new
      allotypic variant of bovine IgG1, designated as IgG1(c) that is distinct in both
      sequence and structure from the known sequence variants.

PMID- 17212765
TI  - Monoclonal antibody against T-cell receptor alphabeta induces self-tolerance in
      chronic experimental autoimmune encephalomyelitis.
AB  - The therapeutic effect of monoclonal antibody (H57-597 MoAb) against T-cell
      receptor (TCR) alphabeta has been investigated on MOG(35-55)-induced experimental
      autoimmune encephalomyelitis (EAE), as a model system for T-cell-mediated chronic
      inflammation in the central nervous system (CNS). Short-term administration of
      the anti-TCR alphabeta immediately after immunization protected the mice from
      EAE. Furthermore, anti-TCR alphabeta treatment on an established disease restored
      the self-tolerance which led to a complete remission of EAE and a dramatic
      reduction of inflammatory cells in the CNS, while treatment with control antibody
      (hamster IgG) was ineffective. The remission was durable and not associated with
      disappearance of autoreactive T cells as measured by persistence of MOG-reactive
      T-cell proliferation in vitro. However, MOG-reactive T cells from anti-TCR
      treated animals produced significantly lower amounts of inflammatory TNF-alpha
      and IFN-gamma. In addition, while a transient deletion of CD4(+) and CD8(+) T
      cells was observed, a population of T cells expressing CD3, NK1.1 and CD69 (NKT
      cells) were expanding. By transfer of spleen cells from anti-TCR MoAb-treated
      animals, we could show that the tolerogenic capacity can be transferred to
      untreated recipients with EAE. The data indicate therapeutic effect of anti-TCR
      alphabeta MoAb (H57-597), which represents a promising approach in treatment of T
      cell-mediated autoimmune diseases.

PMID- 17212766
TI  - Interaction of cholera toxin with three life-cycle stages of Schistosoma mansoni:
      adult worm, egg and cercaria.
AB  - We have previously reported that there is an immunological cross-reactivity
      between Schistosoma mansoni and cholera toxin (CT). In this study, using an
      immunofluorescence technique with anti-CT antibody, we provide further evidence
      for this cross-reactivity by demonstrating an antigen, localized in the tegument
      of S. mansoni adult worms which is cross-reactive with a CT antigen. Anti-CT
      antibodies also reacted with structures in S. mansoni cercariae and eggs.
      Additionally, CT itself was found to bind strongly to the gut of the adult worm,
      gut cells of cercaria and the egg shell. The binding of CT to the parasite was
      blocked when parasite sections were incubated with CT which had been incubated
      with the ganglioside GM1. Lipid extraction and isolation of gangliosides
      demonstrated the presence of GM1 in adult worms. For further analysis of CT
      binding structures, the possible interaction of CT with two major schistosome gut
      antigens, circulating cathodic antigen (CCA) and circulating anodic antigen
      (CAA), was studied. We found that CT blocked the binding of anti-CCA antibody to
      the gut of adult worms and that anti-CCA blocked the binding of CT to the worm
      gut. These findings indicate that CT binds to CCA present in the gut of the
      parasite and thus has, in addition to GM1, a second binding specificity.

PMID- 17212767
TI  - Immunomodulatory role of chloroquine and pyrimethamine in Plasmodium yoelii 17XL
      infected mice.
AB  - Chloroquine (CLQ) and Pyrimethamine (PYR) are used for the treatment of malaria
      and some autoimmune diseases; although their mechanism of action is only
      partially understood, their therapeutic effectiveness in the second case has been
      attributed to their ability to increase apoptosis of T lymphocytes. In view of
      the potential for immunomodulation during malaria chemotherapy, we investigated
      the effects of CLQ and PYR treatment on lymphocyte apoptosis and cytokine
      expression during infection with blood-stage Plasmodium. This work shows that
      infection of BALB/c mice with Plasmodium yoelii 17XL (Py17XL) reduced apoptosis
      in spleen cells but when infected mice were treated with CLQ, apoptosis of B and
      T lymphocytes increased significantly via a Fas-mRNA expression independent
      mechanism associated with downregulation of Bcl-2 expression, whereas treatment
      with PYR increased apoptosis to a lesser extent and only in B lymphocytes. CLQ
      treatment of Py17XL infected mice upregulated tumour necrosis factor-alpha mRNA
      expression, while PYR treatment increased interferon-gamma mRNA expression. In
      infected mice, treatment with CLQ downregulated expression of the anti
      inflammatory cytokines, interleukin-10 and transforming growth factor-beta (TGF
      beta), while PYR treatment upregulated TGF-beta. Thus, in addition to their anti
      malarial effects, both drugs modulate the immune response in malaria by
      increasing apoptosis and modulating the mRNA expression of cytokines involved in
      parasite elimination and regulation of inflammatory responses.

PMID- 17212768
TI  - Partial depletion of CD69low-expressing natural regulatory T cells with the anti
      CD25 monoclonal antibody PC61.
AB  - The role CD4(+) CD25(+) regulatory T cells (Treg) play in modulating the immune
      response has been investigated extensively over recent years. Much of the work to
      date has used the activation marker CD25 to define, enrich and deplete Treg.
      However, the identification of FoxP3 as a definitive marker of Treg has allowed
      us to study the effect of monoclonal antibodies against CD25 on regulatory T-cell
      populations. Recently, published data have indicated that Treg are inactivated,
      not depleted, through treatment with anti-CD25 monoclonal antibody. Using FoxP3
      Green fluorescent protein reporter mice, we show that treatment with the CD25
      MoAb PC61 depleted a subpopulation of Treg. The depleted Treg population
      expressed low levels of the CD69 marker, indicating an inactive phenotype. In
      addition, PC61 treatment altered the function of the remaining regulatory T-cell
      population, preventing their ability to modulate autoimmune diseases. Thus, our
      results have important implications with regard to interpreting experimental
      outcomes from in vivo anti-CD25 treatments.

PMID- 17212769
TI  - Autoantibody-mediated bladder dysfunction in type 1 diabetes.
AB  - Bladder dysfunction is a common complication of diabetic autonomic neuropathy;
      however, its cause remains uncertain. We have recently identified a novel IgG
      autoantibody (Ab) in patients with type 1 diabetes that acts as an agonist at the
      dihydropyridine (DHP) site of L-type voltage-gated calcium channels (VGCC),
      disrupting neuronal regulation of visceral smooth muscle. In the present study,
      passive transfer to mice of IgG from patients with type 1 diabetes was used to
      investigate the role of anti-VGCC Abs in mediating diabetic bladder dysfunction.
      Injection of mice with diabetic immunoglobulin (IgG) with anti-VGCC activity
      induced features of an overactive bladder, including phasic detrusor contractions
      and a loss of bladder wall compliance. The bladder overactivity is mimicked by
      the DHP agonist Bay K8644, reversed by the DHP antagonist nicardipine, but is
      insensitive to the motor nerve blocker tetrodotoxin, indicating that the anti
      VGCC Ab acts at the level of the bladder detrusor itself. This study reports the
      first evidence of Ab-mediated bladder dysfunction in type 1 diabetes, which may
      be part of a wider spectrum of smooth muscle and cardiac abnormalities.

PMID- 17212770
TI  - Abnormal kappa:lambda light chain ratio in circulating immune complexes as a
      marker for B cell activity in juvenile idiopathic arthritis.
AB  - Patients with juvenile idiopathic arthritis (JIA) have been shown to have
      elevated levels of circulating immune complexes (CICs) which correlated with
      disease activity. Our aim was to assess B cell activity by measuring the amount
      of and the kappa:lambda chain immunoglobulin light (L) chain ratio in CICs from
      JIA patients and to determine potential evidence for either an antigen-driven
      response or B-cell receptor editing. We used an enzyme-linked immunosorbent assay
      to measure kappa and lambda chains present in the CICs from the sera of patients
      with JIA. Statistical analysis was performed using Pearson's correlation, one-way
      ANOVA and Bonferroni post hoc analysis. Sera from 44 JIA patients were examined
      for the concentration of L chains in CICs. Healthy controls had a kappa:lambda
      chain ratio of 1.2:1, whereas this ratio was reversed among JIA subgroups with RF
      positive polyarthritis (1:1.2), RF-negative polyarthritis (1:1.3), oligoarthritis
      (1:2.3) and systemic-onset arthritis (1:2.5). In addition, overall lambda chain
      selection was not significantly associated with a particular immunoglobulin heavy
      (H) chain and occurred with all immunoglobulin isotypes. We showed preferential
      selection of lambda chains contributing to the formation of potentially
      pathogenic CICs from JIA patients, of all onset types compared to healthy
      controls, in an H chain-independent manner. The reversal of kappa:lambda chain
      ratio within the JIA CICs and association with all immunoglobulin isotypes
      demonstrated the potential for L chain editing. Furthermore, we conclude that a
      reversal of the normal kappa:lambda chain ratio in JIA CICs may be used as a
      marker for increased B-cell activity.

PMID- 17212771
TI  - Sphingosine 1-phosphate interferes on the differentiation of human monocytes into
      competent dendritic cells.
AB  - Sphingosine 1-phosphate (S1P) is a lipidic messenger known to exert several
      physiological functions within the cell. We tested here whether the stimulation
      of human monocytes with different doses of S1P might interfere with their
      differentiation into competent dendritic cells (DC). Monocytes cultured with
      granulocyte macrophage colony stimulating factor, interleukin-4 (IL-4) and S1P
      differentiated into a DC population lacking CD1a molecules on the surface and
      acquired some aspects of mature DC (mDC), though in the absence of maturation
      stimuli. When stimulated with lipopolisaccharide (LPS), CD1a(-) DC produce high
      amounts of tumour necrosis factor-alpha and IL-10, but not IL-12. Accordingly,
      these CD1a(-) DC were not capable of stimulating allogenic T lymphocytes so well
      as CD1a(+) DC generated from untreated monocytes and maturated with LPS. S1P
      monocyte-derived DC lost their polarizing capacity abrogating the production of
      gamma-interferon/IL-4 by co-cultured naive CD4(+)CD45RA(+) T cells. Our findings
      suggest a mechanism through which S1P can favour the development of immune
      related pathological states.

PMID- 17212772
TI  - A proliferation-inducing ligand (APRIL) is expressed by astrocytes and is
      increased in multiple sclerosis.
AB  - A proliferation-inducing ligand (APRIL) is a newly described member of the tumour
      necrosis factor (TNF) superfamily that was first identified as a factor favouring
      tumorigenesis. APRIL is also important for several immune functions, including B
      cell survival. Multiple sclerosis (MS) is an inflammatory, demyelinating disease
      of the central nervous system (CNS) that is commonly diagnosed in early
      adulthood. Several TNF superfamily members have been identified in brains of
      patients with MS, although their exact function within the CNS is presently
      unknown. To investigate whether APRIL is expressed in the CNS, we studied APRIL
      protein expression by immunohistochemistry in MS patients and controls.
      Morphologically, APRIL-positive cells appeared to be astrocytes. A two-colour
      immunohistochemistry revealed that APRIL expression was cytoplasmic, granular and
      restricted to GFAP-positive cells. Conversely, HLA class II-positive microglial
      cells were negative for APRIL expression. APRIL-positive cells were fewer in
      brains of controls compared with those with MS. We further corroborated our
      findings by studying APRIL protein expression in several glioblastoma cell lines,
      and found APRIL to be expressed by most cell lines analysed. APRIL's binding
      partner syndecan-1 (CD138) was detected in brains of neither MS nor control
      patients. Furthermore, B cells were detectable in the brain of one of five
      patients with MS. We conclude that APRIL is expressed by reactive astrocytes in
      MS and may be of relevance in gliotic scar formation.

PMID- 17212773
TI  - Inflammatory cytokines in relation to adrenal response following total hip
      replacement.
AB  - Our objective was to investigate the initiation and course of pro- and anti
      inflammatory cytokines in early inflammatory response and to elucidate the
      cytokine system in relation to the adrenal response caused by stress. Seven blood
      samples were collected, pre- and postoperatively (0-72 h) after total hip
      replacement (THR) due to osteoarthritis. The following cytokines were measured
      using Cytometric Bead Array: interleukin-1beta (IL-1beta), IL-6, tumour necrosis
      factor-alpha, IL-8, IL-12 and IL-10 (B&D). Thirteen patients took part in the
      study (67 +/- 9 years). C-reactive protein increased from <6 to over 200 mg/l on
      the second post-op day. The concentration of IL-6 increased 10-fold just 3 h post
      op (4-47 pg/ml) and reached its maximum value 6 h post-op (77 pg/ml; Wilcoxon
      test P < 0.01) Repeated measurements were also significant (Friedman P < 0.05).
      The concentration of IL-8 doubled the day of surgery but did not reach a
      significant level (Friedman test =0.069). None of the other cytokines showed any
      significant changes. The diurnal cortisol rhythm was interrupted after the
      surgery and there was a significant correlation between the cortisol secretion
      and IL-6 response. This study demonstrates an isolated elevation in IL-6 levels
      with only a minor elevation in IL-8 following THR. This pro-inflammatory response
      seemed to decline without activation of anti-inflammatory cytokines (IL-10), but
      cortisol seemed to play a complicated role in halting the acute inflammatory
      response.

PMID- 17212774
TI  - Mycobacterium tuberculosis secreted antigen (MTSA-10) modulates macrophage
      function by redox regulation of phosphatases.
AB  - Macrophages are the primary host cells for Mycobacterium tuberculosis (Mtb).
      Although macrophages can mount a strong inflammatory response to dispose of
      invading microbial pathogens, the immune dysfunction of the Mtb-infected
      macrophage constitutes the hallmark of mycobacterial pathogenesis. A 10-kDa, Mtb
      secretory antigen (MTSA-10), encoded by ORF Rv3874, is one of the predominant
      members of the 'region of difference 1' locus of Mtb genome that has been
      strongly implicated in mycobacterial virulence. In this study, we investigated
      the possible role of MTSA-10 in modulating the macrophage dysfunction in a mouse
      macrophage cell line J774.1. We found that recombinant MTSA-10 caused extensive
      protein dephosphorylation in J774.1 cells as revealed by two-dimensional gel
      electrophoresis analysis. We also observed that MTSA-10 treatment downregulated
      the reactive oxygen species levels in the cells leading to activation of cellular
      protein phosphatases putatively responsible for the dephosphorylation phenomenon.
      This implied a direct role of MTSA-10 in the disruption of host cell signaling,
      resulting in downregulation of transcription of several genes essential for
      macrophage function.

PMID- 17212776
TI  - Characterization of a membrane-bound aminopeptidase purified from Acyrthosiphon
      pisum midgut cells. A major binding site for toxic mannose lectins.
AB  - A single membrane-bound aminopeptidase N (APN) occurs in the pea aphid
      (Acyrthosiphon pisum Harris) midgut, with a pH optimum of 7.0, pI of 8.1 and
      molecular mass of 130 kDa. This enzyme accounts for more than 15.6% of the total
      gut proteins. After being solubilized in detergent, APN was purified to
      homogeneity. The enzyme is a glycoprotein rich in mannose residues, which binds
      the entomotoxic lectins of the concanavalin family. The internal sequence of APN
      is homologous with a conservative domain in APNs, and degenerated primers of
      highly conserved APN motifs were used to screen a gut cDNA library. The complete
      sequence of APN has standard residues involved in zinc co-ordination and
      catalysis and a glycosyl-phosphatidylinositol anchor, as in APNs from
      Lepidoptera. APN has a broad specificity towards N-terminal amino acids, but does
      not hydrolyze acidic aminoacyl-peptides, thus resembling the mammalian enzyme (EC
      3.4.11.2). The kcat/Km ratios for different di-, tri-, tetra-, and penta-peptides
      suggest a preference for tripeptides, and that subsites S1, S2' and S3' are
      pockets able to bind bulky aminoacyl residues. Bestatin and amastatin bound APN
      in a rapidly reversible mode, with Ki values of 1.8 microM and 0.6 microM,
      respectively. EDTA inactivates this APN (k(obs) 0.14 M(-1) x s(-1), reaction
      order of 0.44) at a rate that is reduced by competitive inhibitors. In addition
      to oligopeptide digestion, APN is proposed to be associated with amino-acid
      absorption processes which, in contrast with aminopeptidase activity, may be
      hampered on lectin binding.

PMID- 17212775
TI  - DNA polymerase epsilon associates with the elongating form of RNA polymerase II
      and nascent transcripts.
AB  - DNA polymerase epsilon co-operates with polymerases alpha and delta in the
      replicative DNA synthesis of eukaryotic cells. We describe here a specific
      physical interaction between DNA polymerase epsilon and RNA polymerase II,
      evidenced by reciprocal immunoprecipitation experiments. The interacting RNA
      polymerase II was the hyperphosphorylated IIO form implicated in transcriptional
      elongation, as inferred from (a) its reduced electrophoretic mobility that was
      lost upon phosphatase treatment, (b) correlation of the interaction with
      phosphorylation of Ser5 of the C-terminal domain heptapeptide repeat, and (c) the
      ability of C-terminal domain kinase inhibitors to abolish it. Polymerase epsilon
      was also shown to UV crosslink specifically alpha-amanitin-sensitive transcripts,
      unlike DNA polymerase alpha that crosslinked only to RNA-primed nascent DNA.
      Immunofluorescence microscopy revealed partial colocalization of RNA polymerase
      IIO and DNA polymerase epsilon, and immunoelectron microscopy revealed RNA
      polymerase IIO and DNA polymerase epsilon in defined nuclear clusters at various
      cell cycle stages. The RNA polymerase IIO-DNA polymerase epsilon complex did not
      relocalize to specific sites of DNA damage after focal UV damage. Their
      interaction was also independent of active DNA synthesis or defined cell cycle
      stage.

PMID- 17212777
TI  - Discrete conformational changes as regulators of the hydrolytic properties of
      beta-amyloid (1-40).
AB  - Beta-amyloid (1-40) (Abeta), the main component of senile plaques seen in the
      brains of Alzheimer's disease patients, was found to be toxic both as fibrils and
      smaller soluble globular aggregates. The hydrolytic properties of Abeta, a new
      biochemical activity described previously [Brzyska M, Bacia A & Elbaum D (2001)
      Eur J Biochem 268, 3443-3454], may contribute to its overall toxicity. In this
      study, the hydrolysis of fluorescein ester series was studied under predetermined
      conditions affecting Abeta hydrophobicity and conformation. Reaction products of
      the most effectively decomposed ester (dibutyrate) were characterized using HPLC
      and ESI-MS. Hydrophobicity of Abeta, as measured by bis-8-anilinonaphthalene
      fluorescence, correlated with its hydrolytic abilities. FTIR and CD data analysis
      showed a relationship between enhanced hydrolytic abilities and Abeta structure.
      Seriously limited hydrolysis caused by higher peptide concentrations is
      consistent with monomeric/dimeric Abeta species participation in the process,
      confirmed by thioflavine T binding. Inhibition of hydrolysis was caused by beta
      sheet breaker peptide (LPFFD), indicating that the Abeta central hydrophobic
      cluster (amino acids 17-21) participates in the process. The reported Abeta
      properties suggest that small conformational alterations of the peptide structure
      may have a pronounced effect on its functions and biological activity.

PMID- 17212778
TI  - Aberrant interchain disulfide bridge of tissue-nonspecific alkaline phosphatase
      with an Arg433-->Cys substitution associated with severe hypophosphatasia.
AB  - Various mutations in the tissue-nonspecific alkaline phosphatase (TNSALP) gene
      are responsible for hypophosphatasia characterized by defective bone and tooth
      mineralization; however, the underlying molecular mechanisms remain largely to be
      elucidated. Substitution of an arginine at position 433 with a histidine
      [TNSALP(R433H)] or a cysteine [TNSALP(R433C)] was reported in patients diagnosed
      with the mild or severe form of hypophosphatasia, respectively. To define the
      molecular phenotype of the two TNSALP mutants, we sought to examine them in
      transient (COS-1) and conditional (CHO-K1 Tet-On) heterologous expression
      systems. In contrast to an 80 kDa mature form of the wild-type and TNSALP(R433H),
      a unique disulfide-bonded 160 kDa molecular species appeared on the cell surface
      of the cells expressing TNSALP(R433C). Sucrose density gradient centrifugation
      demonstrated that TNSALP(R433C) forms a disulfide-bonded dimer, instead of being
      noncovalently assembled like the wild-type. Of the five cysteine residues per
      subunit of the wild-type, only Cys102 is thought to be present in a free form.
      Replacement of Cys102 with serine did not affect the dimerization state of
      TNSALP(R433C), implying that TNSALP(R433C) forms a disulfide bridge between the
      cysteine residues at position 433 on each subunit. Although the cross-linking did
      not significantly interfere with the intracellular transport and cell surface
      expression of TNSALP(R433C), it strongly inhibited its alkaline phosphatase
      activity. This is in contrast to TNSALP(R433H), which shows enzyme activity
      comparable to that of the wild-type. Importantly, addition of dithiothreitol to
      the culture medium was found to partially reduce the amount of the cross-linked
      form in the cells expressing TNSALP(R433C), concomitantly with a significant
      increase in enzyme activity, suggesting that the cross-link between two subunits
      distorts the overall structure of the enzyme such that it no longer efficiently
      carries out its catalytic function. Increased susceptibility to proteases
      confirmed a gross conformational change of TNSALP(R433C) compared with the wild
      type. Thus, loss of function resulting from the interchain disulfide bridge is
      the molecular basis for the lethal hypophosphatasia associated with
      TNSALP(R433C).

PMID- 17212779
TI  - Mutational analysis of substrate recognition by human arginase type I--agmatinase
      activity of the N130D variant.
AB  - Upon mutation of Asn130 to aspartate, the catalytic activity of human arginase I
      was reduced to approximately 17% of wild-type activity, the Km value for arginine
      was increased approximately 9-fold, and the kcat/Km value was reduced
      approximately 50-fold. The kinetic properties were much less affected by
      replacement of Asn130 with glutamine. In contrast with the wild-type and N130Q
      enzymes, the N130D variant was active not only on arginine but also on its
      decarboxylated derivative, agmatine. Moreover, it exhibited no preferential
      substrate specificity for arginine over agmatine (kcat/Km values of 2.48 x 10(3)
      M(-1) x s(-1) and 2.14 x 10(3) M(-1) x s(-1), respectively). After dialysis
      against EDTA and assay in the absence of added Mn2+, the N130D mutant enzyme was
      inactive, whereas about 50% full activity was expressed by the wild-type and
      N130Q variants. Mutations were not accompanied by changes in the tryptophan
      fluorescence properties, thermal stability or chromatographic behavior of the
      enzyme. An active site conformational change is proposed as an explanation for
      the altered substrate specificity and low catalytic efficiency of the N130D
      variant.

PMID- 17212780
TI  - Characterization of SCP-2 from Euphorbia lagascae reveals that a single Leu/Met
      exchange enhances sterol transfer activity.
AB  - Sterol carrier protein-2 (SCP-2) is a small intracellular basic protein domain
      implicated in peroxisomal beta-oxidation. We extend our knowledge of plant SCP-2
      by characterizing SCP-2 from Euphorbia lagascae. This protein consists of 122
      amino acids including a PTS1 peroxisomal targeting signal. It has a molecular
      mass of 13.6 kDa and a pI of 9.5. It shares 67% identity and 84% similarity with
      SCP-2 from Arabidopsis thaliana. Proteomic analysis revealed that E. lagascae SCP
      2 accumulates in the endosperm during seed germination. It showed in vitro
      transfer activity of BODIPY-phosphatidylcholine (BODIPY-PC). The transfer of
      BODIPY-PC was almost completely inhibited after addition of phosphatidylinositol,
      palmitic acid, stearoyl-CoA and vernolic acid, whereas sterols only had a very
      marginal inhibitory effect. We used protein modelling and site-directed
      mutagenesis to investigate why the BODIPY-PC transfer mediated by E. lagascae SCP
      2 is not sensitive to sterols, whereas the transfer mediated by A. thaliana SCP-2
      shows sterol sensitivity. Protein modelling suggested that the ligand-binding
      cavity of A. thaliana SCP-2 has four methionines (Met12, 14, 15 and 100), which
      are replaced by leucines (Leu11, 13, 14 and 99) in E. lagascae SCP-2. Changing
      Leu99 to Met99 was sufficient to convert E. lagascae SCP-2 into a sterol
      sensitive BODIPY-PC-transfer protein, and correspondingly, changing Met100 to
      Leu100 abolished the sterol sensitivity of A. thaliana SCP-2.

PMID- 17212781
TI  - Subunit composition and in vivo substrate-binding characteristics of Escherichia
      coli Tat protein complexes expressed at native levels.
AB  - The Tat system transports folded proteins across the bacterial cytoplasmic
      membrane and the thylakoid membrane of plant chloroplasts. Substrates are
      targeted to the Tat pathway by signal peptides containing a pair of consecutive
      arginine residues. The membrane proteins TatA, TatB and TatC are the essential
      components of this pathway in Escherichia coli. The complexes that these proteins
      form at native levels of expression have been investigated by the use of affinity
      tag-coding sequences fused to chromosomal tat genes. Distinct TatA and TatBC
      complexes were identified using size-exclusion chromatography and shown to have
      apparent molecular masses of approximately 700 and 500 kDa, respectively.
      Following in vivo expression, the Tat substrate protein SufI was found to
      copurify with the TatBC, but not the TatA, complex. This binding required the
      SufI signal peptide. Substitution of the twin-arginine residues in the SufI
      signal peptide by either twin lysine or twin alanine residues abolished export.
      However, both variant SufI proteins still copurified with the TatBC complex.
      These data show that the twin-arginine residues of the Tat consensus motif are
      not essential for binding of precursor to the TatBC complex but are required for
      the successful entry of the precursor into the transport cycle. The effect on
      substrate binding of single amino acid substitutions in TatC that affect Tat
      transport were studied using TatC variants Phe94Ala, Glu103Ala, Glu103Arg and
      Asp211Ala. Only variant Glu103Arg showed reduced copurification of SufI with
      TatBC. The transport defects associated with the other TatC variants do not,
      therefore, arise from an inability to bind substrate proteins.

PMID- 17212782
TI  - Molecular cloning and characterization of the crustacean hyperglycemic hormone
      cDNA from Litopenaeus schmitti. Functional analysis by double-stranded RNA
      interference technique.
AB  - The crustacean hyperglycemic hormone (CHH) plays an important role in the
      regulation of hemolymph glucose levels, but it is also involved in other
      functions such as growth, molting and reproduction. In the present study we
      describe the first CHH family gene isolated from the Atlantic Ocean shrimp
      Litopenaeus schmitti. Sequence analysis of the amplified cDNA fragment revealed a
      high nucleotide sequence identity with other CHHs. Northern blot analysis showed
      that the isolated CHH mRNA from L. schmitti is present in the eyestalk but not in
      muscle or stomach. We also investigated the ability of dsRNA to inhibit the CHH
      function in shrimps in vivo. Injection of CHH dsRNA into the abdominal hemolymph
      sinuses resulted in undetectable CHH mRNA levels within 24 h and a corresponding
      decrease in hemolymph glucose levels, suggesting that functional gene silencing
      had occurred. These findings are the first evidence that dsRNA technique is
      operative in adult shrimps in vivo.

PMID- 17212783
TI  - IMP1 interacts with poly(A)-binding protein (PABP) and the autoregulatory
      translational control element of PABP-mRNA through the KH III-IV domain.
AB  - Repression of poly(A)-binding protein (PABP) mRNA translation involves the
      formation of a heterotrimeric ribonucleoprotein complex by the binding of PABP,
      insulin-like growth factor II mRNA binding protein-1 (IMP1) and the unr gene
      encoded polypeptide (UNR) to the adenine-rich autoregulatory sequence (ARS)
      located at the 5' untranslated region of the PABP-mRNA. In this report, we have
      further characterized the interaction between PABP and IMP1 with the ARS at the
      molecular level. The dissociation constants of PABP and IMP1 for binding to the
      ARS RNA were determined to be 2.3 nM and 5.9 nM, respectively. Both PABP and IMP1
      interact with each other, regardless of the presence of the ARS, through the
      conserved C-terminal PABP-C and K-homology (KH) III-IV domains, respectively.
      Interaction of PABP with the ARS requires at least three out of its four RNA
      binding domains, whereas KH III-IV domain of IMP1 is necessary and sufficient for
      binding to the ARS. In addition, the strongest binding site for both PABP and
      IMP1 on the ARS was determined to be within the 22 nucleotide-long
      CCCAAAAAAAUUUACAAAAAA sequence located at the 3' end of the ARS. Results of our
      analysis suggest that both protein x protein and protein x RNA interactions are
      involved in forming a stable ribonucleoprotein complex at the ARS of PABP mRNA.

PMID- 17212784
TI  - A designed curved DNA segment that is a remarkable activator of eukaryotic
      transcription.
AB  - To identify artificial DNA segments that can stably express transgenes in the
      genome of host cells, we built a series of curved DNA segments that mimic a left
      handed superhelical structure. Curved DNA segments of 288 bp (T32) and 180 bp
      (T20) were able to activate transcription from the herpes simplex virus thymidine
      kinase (tk) promoter by approximately 150-fold and 70-fold, respectively,
      compared to a control in a transient transfection assay in COS-7 cells. The T20
      segment was also able to activate transcription from the human adenovirus type 2
      E1A promoter with an 18-fold increase in the same assay system, and also
      activated transcription from the tk promoter on episomes in COS-7 cells. We also
      established five HeLa cell lines with genomes containing T20 upstream of the
      transgene promoter and control cell lines with T20 deleted from the transgene
      locus. Interestingly, T20 was found to activate transcription in all the stable
      transformants, irrespective of the locus. This suggests that the T20 segment may
      allow stable expression of transgenes, which is of importance in many fields, and
      may also be useful for the construction of nonviral vectors for gene therapy.

PMID- 17212785
TI  - Phytochelatin-cadmium-sulfide high-molecular-mass complexes of Euglena gracilis.
AB  - High-molecular-mass PC complexes (PC-HMWCs) constituted by phytochelatins (PCs),
      cadmium and sulfide are synthesized by several organisms after exposure to
      cadmium. In this study, PC-HMWCs were isolated from photoheterotrophic Euglena
      gracilis and purified to homogeneity, resulting in compounds of molecular mass 50
      380 kDa depending on the CdCl2 and sulfate concentrations in the culture medium.
      In contrast with plants and some yeasts, PC-HMWCs from E. gracilis mainly
      comprise (57-75%) monothiol molecules (Cys, gamma-glutamylcysteine, GSH) and, to
      a lesser extent (25-43%), PCs. A similar acid-soluble thiol compound composition
      was found in whole cell extracts. The -SH/Cd2+ and S2-/Cd2+ ratios found in
      purified PC-HMWCs were 1.5 and 1.8, respectively; the (-SH + S2-)/Cd2+ ratio was
      3.2. PC-HMWCs of molecular mass 60 and 100 kDa were also localized inside Percoll
      purified chloroplasts, in which cadmium and PCs were mainly compartmentalized.
      Cadmium and sulfur-rich clusters with similar sulfur/cadmium stoichiometries to
      those of the purified PC-HMWCs were detected in the chloroplast and throughout
      the cell by energy dispersive microanalysis and atomic resolution electron
      microscopy. The presence of PC-HMWCs in primitive photosynthetic eukaryotes such
      as the protist, E. gracilis, suggests that their function as the final cadmium
      storage-inactivation process is widespread. Their particular intracellular
      localization suggests that chloroplasts may play a major role in the cadmium
      resistance mechanism in organisms lacking a plant-like vacuole.

PMID- 17212786
TI  - Ixocarpalactone A isolated from the Mexican tomatillo shows potent
      antiproliferative and apoptotic activity in colon cancer cells.
AB  - Physalis philadelphica Lam, commonly known as a tomatillo, is a staple of the
      Mesoamerican cuisine. In our laboratory, an ethyl acetate-soluble extract and
      four withanolides [ixocarpalactone A (IxoA), ixocarpalactone B,
      philadelphicalactone B, and withaphysacarpin] were isolated. Studies conducted on
      Hepa-1c1c7 hepatoma cells revealed that withanolides were potent inducers of
      quinone reductase, suggesting possible cancer chemoprotective activity. Here we
      evaluated the antiproliferative properties of the withanolides in SW480 human
      colon cancer cells. IxoA, which is present in the edible part of the tomatillo,
      was selected for further evaluation. SW480 cells treated with IxoA showed cell
      cycle arrest in the G2/M phase, up-regulation of hyper-phosphorylated
      retinoblastoma, and down-regulation of E2F-1 and DP-1. On the basis of flow
      cytometry analysis, ethidium bromide/acridine orange, and 4',6-diamidino-2
      phenylindole staining, it was found that IxoA induces apoptosis in SW480 cells.
      Moreover, increased concentrations of the pro-apoptotic protein, BIM/BOD, were
      found by western blot analysis and immunocytochemistry. Morphological examination
      revealed vacuole formation in cells treated with IxoA, and Oil Red O staining
      showed that the vacuole content was nonlipid. Furthermore, immunocytochemistry
      demonstrated increased concentrations of mucin 3 in IxoA-treated SW480 cells.
      These findings suggest that chemicals present in tomatillos (e.g. IxoA) may have
      cancer chemopreventive properties.

PMID- 17212787
TI  - The minimal amyloid-forming fragment of the islet amyloid polypeptide is a
      glycolipid-binding domain.
AB  - Several proteins that interact with cell surface glycolipids share a common fold
      with a solvent-exposed aromatic residue that stacks onto a sugar ring of the
      glycolipid (CH-pi stacking interaction). Stacking interactions between aromatic
      residues (pi-pi stacking) also play a pivotal role in the assembly process,
      including many cases of amyloid fibril formation. We found a structural
      similarity between a typical glycolipid-binding domain (the V3 loop of HIV-1
      gp120) and the minimal amyloid-forming fragment of the human islet amyloid
      polypeptide, i.e. the octapeptide core module NFGAILSS. In a monolayer assay at
      the air-water interface, the NFGAILSS peptide specifically interacted with the
      glycolipid lactosylceramide. The interaction appears to require an aromatic
      residue, as NLGAILSS was poorly recognized by lactosylceramide, whereas NYGAILSS
      behaved like NFGAILSS. In addition, we observed that the full-length human islet
      amyloid polypeptide (1-37) did interact with a monolayer of lactosylceramide, and
      that the glycolipid film significantly affected the aggregation process of the
      peptide. As glycolipid-V3 interactions are efficiently inhibited by suramin, a
      polyaromatic compound, we investigated the effects of suramin on amyloid
      formation by human islet amyloid polypeptide. We found that suramin inhibited
      amyloid fibril formation at low concentrations, but dramatically stimulated the
      process at high concentrations. Taken together, our results indicate that the
      minimal amyloid-forming fragment of human islet amyloid polypeptide is a
      glycolipid-binding domain, and provide further experimental support for the role
      of aromatic pi-pi and CH-pi stacking interactions in the molecular control of the
      amyloidogenesis process.

PMID- 17212790
TI  - Prevalence of obesity, central obesity and the associated factors in urban
      population aged 20-70 years, in the north of Iran: a population-based study and
      regression approach.
AB  - Obesity is an undesirable outcome of changing of lifestyle and behaviours. It is
      also reversible predisposing factor for the development of several debilitating
      diseases. This study was aimed to determine the prevalence rate of obesity,
      overweight, central obesity and their associated factors in the north of Iran. We
      conducted a population-based cross-sectional study with a sample of 1800 women
      and 1800 men with respective mean ages of 37.5 +/- 13.0 and 38.5 +/- 14.2 years
      of urban population aged 20-70 years living in the north of Iran. The demographic
      and lifestyle data, in particular, age, gender, marital status, marriage age,
      family history of obesity, educational level, occupation, occupational and
      leisure time physical activity, duration of exercise per week, parity and the
      number of children were collected with a designed questionnaire. Diagnosis of
      obesity and central obesity were confirmed by the WHO standard recommended method
      by determining of body mass index (BMI) and waist circumference (WC). Logistic
      regression model was used to estimate the adjusted odds ratio (OR) and its 95%
      confidence interval. Over half of the study subjects were at educational levels
      of high school or higher; 79.4% of population was married and 35.3% had a family
      history of parental obesity. The majority of subjects in particular women had
      none or low levels of physical activity. The overall prevalence rates of obesity
      and overweight were 18.8% and 34.8% respectively. The overall prevalence rate of
      central obesity was 28.3%. The rate of obesity in women was higher than men (P <
      0.0001). In both genders, particularly in the women, the rate of obesity was
      raised by increasing age. There was an inverse relation between the risk of
      obesity and marriage age, the high level of education (OR = 0.19, P < 0.0001),
      severe occupational activity (OR = 0.44, P < 0.0001), the level of exercise (in
      subjects with 3-4 h exercise per week, OR = 0.58, P < 0.001) and leisure time
      activity. Marriage, history of parental obesity and parity > or =5 were
      associated with increased risk of obesity (OR = 2.2, P < 0.001 and OR = 2.43, P <
      0.0001 and OR = 3.73, P < 0.0001 respectively). The results of this study
      indicate an increased rate of obesity and overweigh in the north population of
      Iran. With respect to these findings, low level of activity and education,
      parity, family history of obesity, marriage at earlier age and ageing are
      responsible for both obesity and central obesity in the north of Iran. Therefore,
      a community-based multiple strategies are required to combat with increasing rate
      of obesity and its subsequent complications such as diabetes, coronary artery
      disease, hypertension and osteoarthritis.

PMID- 17212791
TI  - Prevalence of obesity in Morocco.
AB  - Data on measured heights and weights indicate that the prevalence of obesity has
      increased among Moroccan population over the past 15 years. In 1984/1985, 4.1% of
      the adult population was obese, and the prevalence increased to 10.3% in
      1998/1999. In the most recent survey in the year 2000, 13.3% of individuals aged
      20 years and more were obese (22% among women and 8% among men). Excessive weight
      is more prevalent in urban than in rural areas, varies by geographical residence,
      positively associated with age and negatively with education level. The
      increasing prevalence of obesity poses challenges for researchers and policy
      makers.

PMID- 17212792
TI  - Prevalence of overweight and obesity among children in the United Arab Emirates.
AB  - The aim of the study was to determine the prevalence of overweight and obesity in
      children in the United Arab Emirates (UAE). Secondary analysis was undertaken of
      data on 4381 children aged 5-17 years from the 1999 UAE-National Iodine
      Deficiency Surveillance Study. Data on weight and height from that study were
      used to calculate body mass index. The prevalence of overweight and obesity was
      estimated using International Obesity Task Force criteria. Overall, 944 (21.5%)
      of children were overweight and 601 (13.7%) of these were obese. More girls than
      boys were overweight (22.9% vs. 20.2%; P < or = 0.001). Non-citizen girls were
      more likely to be obese (odds ratios [OR] 1.767, 95% confidence intervals [CI]
      1.48-2.102) than UAE girls. Boys in the rural areas had the lowest prevalence
      (23.6%) and were the least likely of all the children to be either overweight (OR
      0.785, 95% CI 0.629-0.974) or obese 0.732 (95% CI 0.591-0.912). This study
      demonstrates a high prevalence of overweight in children in the UAE. Prompt
      actions are needed to initiate preventative and interventionist strategies to
      reverse the trend of this emerging epidemic.

PMID- 17212793
TI  - The role of leptin and ghrelin in the regulation of food intake and body weight
      in humans: a review.
AB  - Leptin and ghrelin are two hormones that have been recognized to have a major
      influence on energy balance. Leptin is a mediator of long-term regulation of
      energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin
      on the other hand is a fast-acting hormone, seemingly playing a role in meal
      initiation. As a growing number of people suffer from obesity, understanding the
      mechanisms by which various hormones and neurotransmitters have influence on
      energy balance has been a subject of intensive research. In obese subjects the
      circulating level of the anorexigenic hormone leptin is increased, whereas
      surprisingly, the level of the orexigenic hormone ghrelin is decreased. It is now
      established that obese patients are leptin-resistant. However, the manner in
      which both the leptin and ghrelin systems contribute to the development or
      maintenance of obesity is as yet not clear. The purpose of this review is to
      provide background information on the leptin and ghrelin hormones, their role in
      food intake and body weight in humans, and their mechanism of action. Possible
      abnormalities in the leptin and ghrelin systems that may contribute to the
      development of obesity will be mentioned. In addition, the potentials of leptin
      and ghrelin as drug targets will be discussed. Finally, the influence of the diet
      on leptin and ghrelin secretion and functioning will be described.

PMID- 17212794
TI  - Obesity and the heart: redefinition of the relationship.
AB  - Although obesity is an important cardiovascular risk factor, growing evidence
      shows that obesity is not always related to an unfavourable cardio-metabolic
      profile or poor cardiac outcomes. Recent studies show that excess fat even in the
      absence of comorbidities (uncomplicated obesity) can lead to adaptive cardiac
      morphological and functional changes. Uncomplicated obesity represents a well
      defined clinical entity that should be carefully considered and followed up. The
      existence of metabolically healthy subjects presenting a lower prevalence of
      cardiac modifications and risk factors strongly suggests that a redefinition of
      obesity based on regional fat distribution indices like waist-to-hip ratio
      instead of body mass index is warranted.

PMID- 17212795
TI  - Elevated body mass index and mortality risk in the elderly.
AB  - The purpose of this report was to perform a systematic review and meta-analysis
      of the studies examining the impact of an elevated body mass index (BMI) on
      mortality risk in elderly (> or =65 years) men and women. A variance-based method
      of meta-analysis was used to summarize the relationships from available studies.
      The summary relative risk of all-cause mortality from the 26 analyses that
      included a risk estimate for a BMI within the overweight range was 1.00 (95%
      confidence intervals, 0.97-1.03). The summary relative risk of all-cause
      mortality for the 28 analyses that included a risk estimate for a BMI within the
      obese range was 1.10 (1.06-1.13). These calculations indicate that a BMI in the
      overweight range is not associated with a significantly increased risk of
      mortality in the elderly, while a BMI in the moderately obese range is only
      associated with a modest increase in mortality risk.

PMID- 17212796
TI  - An integrative review of Canadian childhood obesity prevention programmes.
AB  - To examine successful Canadian nursing and health promotion intervention
      programmes for childhood obesity prevention during gestation and infancy, an
      integrative review was performed of the literature from 1980 to September 2005.
      The following databases were used: PubMed; Cochrane Database of Systematic
      Reviews; Cochrane Controlled Trials Register; Database of Abstracts of Reviews of
      Effects; ACP Journal Club; MEDLINE; EMBASE; CINAHL; Web of Science; Scopus;
      Sociological Abstracts; Sport Discus; PsycInfo; ERIC and HealthStar. MeSH
      headings included: infancy (0-24 months), gestation, gestational diabetes,
      nutrition, prenatal care, pregnancy, health education, pregnancy outcome, dietary
      services with limits of Canadian, term birth. Of 2028 articles found, six
      Canadian childhood obesity prevention programmes implemented during gestation
      and/or infancy were found; three addressed gestational diabetes with five
      targeting low-income Canadian urban and/or Aboriginal populations. No
      intervention programmes specifically aimed to prevent childhood obesity during
      gestation or infancy. This paucity suggests that such a programme would be
      innovative and much needed in an effort to stem the alarming increase in obesity
      in children and adults. Any attempts either to develop new approaches or to
      replicate interventions used with obese adults or even older children need
      careful evaluation and pilot testing prior to sustained use within the perinatal
      period.

PMID- 17212797
TI  - Do interventions to limit sedentary behaviours change behaviour and reduce
      childhood obesity? A critical review of the literature.
AB  - We sought to determine whether interventions that emphasize decreasing sedentary
      behaviours in children and adolescents result in behaviour change and weight
      control. A comprehensive literature search was conducted to identify all
      comparative studies of interventions to reduce sedentary behaviour among
      children, alone or in combination with other health messages. Two investigators
      evaluated articles for eligibility and validity. As methods, settings and
      interventions differ across studies, results were synthesized narratively. Twelve
      studies met the inclusion criteria and provided relevant data. Six targeted
      clinic-based populations that were overweight or at risk of overweight, and six
      were population-based prevention studies. Approaches varied, but all reduced
      sedentary behaviour and improved weight indices. An emphasis on decreasing
      sedentary behaviours is an effective intervention to decrease sedentary
      behaviours and control weight in children and adolescents.

PMID- 17212800
TI  - Childhood overweight: is there need for a new societal approach to the obesity
      epidemic?

PMID- 17212802
TI  - Preliminary investigations on the standardisation and quality control for the
      determination of gamma-glutamyltranspeptidase activity in seminal plasma.
AB  - The present study was designed to assess the effects of centrifugation velocity,
      standing time after dilution, freezing-thawing and chymotrypsin on the
      determination of gamma-glutamyltranspeptidase (gamma-GT) activities in seminal
      plasma, and to establish an instruction for the standardisation and quality
      control for the determination of gamma-GT within the same laboratory and among
      different laboratories. The gamma-GT level and sperm concentration of each of 72
      samples of seminal plasma obtained by centrifugation at 1000 g for 10 min or 3000
      g for 15 min were assayed. In addition, gamma-GT activities in diluted seminal
      plasma with different standing time and in samples with or without chymotrypsin
      were measured. The results showed that there was a significant difference of
      gamma-GT levels in seminal plasma obtained by centrifugation at different
      velocities (P < 0.001), and that gamma-GT activities in seminal plasma measured
      after standing for 30 min after dilution were notably lower than those measured
      immediately after dilution (P < 0.001). However, the data indicated that both
      chymotrypsin and freezing-thawing had no apparent effect on the determination of
      seminal gamma-GT. In conclusion, standing time after dilution and centrifugation
      velocity should be standardised, and frozen seminal plasma could serve as quality
      control products for the determination of gamma-GT activity among different
      laboratories.

PMID- 17212803
TI  - The influence of homogenous zona pellucida on human spermatozoa hyperactivation,
      acrosome reaction and zona binding.
AB  - The study aimed to evaluate the changes in sperm motion characteristics and the
      occurrence of hyperactivation among sperm populations after exposure to human
      zona pellucida. Motile spermatozoa samples were used to evaluate the sperm-zona
      binding capacity, zona-induced acrosome reaction and changes in sperm motion
      characteristics. Sperm motion characteristic changes studied included straight
      line velocity, curvilinear velocity, amplitude of lateral head displacement,
      straightness and beat cross frequency. Recordings were performed on semen
      immediately after liquefaction, 3 h capacitation and after exposure to
      solubilised human zona pellucida. The semen samples were divided into morphology
      categories, namely six (16 +/- 1.4% normal forms, normal patterns), 31 (8 +/-
      1.7% normal forms, G-pattern) and 27 (3 +/- 1.3% normal forms, P-pattern). The
      Hemizona Indices for the three morphology groups namely normal, G-patterns and P
      patterns, were 77 +/- 6%, 61 +/- 5% and 41 +/- 5% respectively (P <or= 0.05). The
      zona-induced acrosome reaction for the three groups were 25.0 +/- 2% (normal
      group), 18.0 +/- 2% (G-patterns) and 14.1 +/- 0.6% (P-pattern) (P <or= 0.05). The
      number of hyperactivated sperm showed an increase in the ejaculates (1%), after
      capacitation (2%) and exposure to zona pellucida (5%) (P <or= 0.05). When divided
      into the three morphology groups, the number of spermatozoa with hyperactivated
      motility was more profound in men with normal morphology compared with G- and P
      pattern men. Human zona pellucida is a strong inducer of hyperactivated motility
      among spermatozoa and the effect is more profound among sperm populations with
      normal morphology.

PMID- 17212804
TI  - Tadalafil as an in vitro sperm motility stimulant.
AB  - Tadalafil (Cialis) is a known oral selective phosphodiesterase-5 inhibitor used
      widely in the management of erectile dysfunction. To assess its ability on human
      sperm motility in vitro, 70 asthenozoospermic semen specimens delivered by
      masturbation were investigated. Semen samples were divided equally into four
      tubes, one as a control and to the others tadalafil dissolved solution was added
      in vitro in three different concentrations (4.0, 1.0, 0.5 mg ml(-1)
      respectively). The tubes were incubated and were followed up for sperm motility
      per cent changes for 0.5, 1, 2, 3 h. It was found that the concentration used
      played an important role in the degree of sperm enhancement. Specimens treated
      with 4 mg ml(-1) tadalafil solution demonstrated a significant decrease in sperm
      motility compared with the controls. Specimens treated with 1.0 mg ml(-1)
      solution demonstrated significant increase in sperm progressive forward motility.
      Specimens treated with 0.5 mg ml(-1) solution demonstrated significant increases
      in sperm motility but lower than that of 1 mg ml(-1) concentration. It is
      concluded that in vitro use of tadalafil solution in special concentration has a
      significant stimulatory effect on asthenozoospermic sperm motility.

PMID- 17212805
TI  - Incidence of changes and predictive factors for sexual function after coronary
      stenting.
AB  - The study was aimed at determining the incidence of changes in sexual function
      and identifying the possible associated variables of erectile dysfunction (ED) in
      coronary artery disease (CAD) patients undergoing coronary stenting. Four hundred
      and sixty-seven patients were retrospectively contacted with a questionnaire
      regarding sexual function from 6 months pre-stenting to 6 months post-stenting by
      telephone follow up. Univariate analyses were used to determine prognostic
      variables. ED changed following stenting in CAD (P < 0.05), in acute coronary
      syndrome (ACS) (P > 0.05) and in chronic coronary syndrome (CCS) (P < 0.05).
      Sexual activity was not resumed in 8.1%, was unchanged in 33.8%, increased in 0%
      and decreased in 58.0%. The average frequency of sexual activity decreased every
      month in CAD (P < 0.05), in ACS (P < 0.05) and in CCS (P < 0.01) after undergoing
      coronary stenting respectively. The mean time interval between the onset of ED
      and CAD was 33 months. Resuming sexual activity after stenting varied from 2
      weeks to 30 months. Significant predictors of ED after coronary stenting were
      mean age, diabetes mellitus, 2,3-vessel disease or current smoking status. It was
      concluded that coronary stenting had a significant incidence of ED. Mean age,
      diabetes mellitus, 2,3-vessel disease or current smoking status showed to be the
      main variables associated with ED. Attempts to improve individual secondary
      prevention outcomes (controlling serum glucose and smoking cessation) should be
      designed.

PMID- 17212806
TI  - Expression of leptin and leptin receptor in the testis of fertile and infertile
      patients.
AB  - The aim of our study was to investigate the relationships between the expression
      of leptin, leptin receptor in the testis and spermatogenesis, and testosterone
      (T) concentration in infertile men. Testicular tissue samples were collected from
      the testes of five fertile volunteers, eight patients with obstructive
      azoospermia (OA), six patients with Sertoli cell-only syndrome (SCO) and 32
      oligospermic patients with varicocele testis. In testicular tissue, leptin and
      leptin receptor were identified by staining with polyclonal antibodies. Serum
      follicle stimulating hormone, lutenising hormone (LH), and T were determined by
      chemiluminescence assays. Leptin was expressed on germ cells, mainly on
      spermatocytes. The ratio of immunostained germ cells to total germ cells was
      inversely correlated with the concentration of T (r = -0.32, P = 0.01), sperm
      concentration (r = -0.51, P = 0.002) and Johnsen's score (r = -0.44,P = 0.005).
      In contrast, leptin receptor immunostained cells were found in the interstitium,
      primarily in Leydig cells. Leptin receptor expression on Leydig cells was
      inversely correlated with serum T concentration (r = -0.50, P < 0.001). The
      dysfunction of spermatogenesis is associated with an increase in leptin and
      leptin receptor expression in the testis.

PMID- 17212807
TI  - alpha-1,4-Glucosidase activity in infertile oligoasthenozoospermic men with and
      without varicocele.
AB  - This work aimed to assess seminal alpha-1,4-glucosidase activity in infertile
      oligoasthenozoospermic men associated with and without scrotal varicocele. Eighty
      men were investigated. They were divided into three groups: group 1 (n = 20),
      fertile normozoospermic men; group 2 (n = 30), oligoasthenozoospermia with
      varicocele; and group 3 (n = 30), oligoasthenozoospermia without varicocele. The
      patients underwent medical history, clinical examination, conventional semen
      analysis and estimation of seminal plasma alpha-1,4-glucosidase activity by
      double-beam spectrophotometer method and serum testosterone by radioimmunoassay
      method. There was a significant decrease in the mean seminal alpha-1,4
      glucosidase activity levels in infertile men versus controls (mean +/- SD; 7.66
      +/- 0.433, 2.088 +/- 0.565, 5.384 +/- 0.85 mU ml(-1) respectively). Mean serum
      testosterone levels demonstrated nonsignificant differences between studied
      groups. Seminal alpha-1,4-glucosidase activity levels demonstrated significant
      correlation with sperm count, sperm motility percentage and serum testosterone in
      oligoasthenozoospermia with varicocele group and demonstrated nonsignificant
      correlation in other groups. It is concluded that varicocele-induced hypoxia is
      the adverse effect that causes both oligoasthenozoospermia and decreased seminal
      alpha-1,4-glucosidase levels.

PMID- 17212808
TI  - Semen and the diagnosis of infertility in Aristotle.
AB  - Aristotle (384-322bc) was one of the leading intellectual figures of all time. In
      his work he systematised a massive amount of knowledge on a diverse range of
      subjects, including medicine. This article discusses the observations and
      hypotheses of this great philosopher on semen and infertility, as they are
      presented in his work Generation of Animals. This is combined with an evaluation
      of his positions in relation to those of the Hippocratic Corpus on the same
      subject. An extensive review of Aristotle's work Generation of Animals was
      performed with particular focus on his perspectives about semen and infertility.
      Publications referring to this work were also reviewed. According to Aristotle,
      semen is that which contains the principles that come from both parents when they
      unite. He believed that semen was formed by the secretion of nutriments by the
      body, developing his theories of sterility on this basic principle. A lack of
      fertility is attributed to genetic or acquired causes. He proposed methods for
      diagnosing sterility, primarily the 'water test' for men and the 'pessary' method
      for women. Even if his observations contain clear mistakes, such as attributing
      only secondary functions to male testicles and the identification of menses as
      women's 'seed', Aristotle's views also contain keen observations and exceptional
      thinking, both on the characteristics of semen and the causes of sterility
      (infertility).

PMID- 17212809
TI  - Fertilisation failure after intracytoplasmic sperm injection is not associated
      with sperm aneuploidy of a globozoospermic patient.
AB  - The objective of this study was to determine the aneuploidy rate in spermatozoa
      from a globozoospermic patient who underwent three unsuccessful intracytoplasmic
      sperm injection (ICSI) treatment cycles together with his wife. The aneuploidy
      rates of chromosomes 13, 18, 21, X and Y as well as the diploidy rate in the
      spermatozoa of this man were evaluated by fluorescence in situ hybridisation to
      clarify if chromosomal aneuploidy could be a cause for the low fertilisation rate
      observed in this case. In the spermatozoa of our patient no increase in
      aneuploidy rates was found for the tested chromosomes (0.0% disomies of
      chromosomes 13, 18 and 21 with a diploidy rate of 0.6%; X/Y missegregation: 0.6%)
      indicating that the ICSI outcome of the couple was not impaired by sperm
      aneuploidy of the globozoospermic man.

PMID- 17212810
TI  - Crystal structure of an FIV/HIV chimeric protease complexed with the broad-based
      inhibitor, TL-3.
AB  - We have obtained the 1.7 A crystal structure of FIV protease (PR) in which 12
      critical residues around the active site have been substituted with the
      structurally equivalent residues of HIV PR (12X FIV PR). The chimeric PR was
      crystallized in complex with the broad-based inhibitor TL-3, which inhibits wild
      type FIV and HIV PRs, as well as 12X FIV PR and several drug-resistant HIV
      mutants 1234. Biochemical analyses have demonstrated that TL-3 inhibits these PRs
      in the order HIV PR > 12X FIV PR > FIV PR, with Ki values of 1.5 nM, 10 nM, and
      41 nM, respectively 234. Comparison of the crystal structures of the TL-3
      complexes of 12X FIV and wild-typeFIV PR revealed theformation of additinal van
      der Waals interactions between the enzyme inhibitor in the mutant PR. The 12X FIV
      PR retained the hydrogen bonding interactions between residues in the flap
      regions and active site involving the enzyme and the TL-3 inhibitor in comparison
      to both FIV PR and HIV PR. However, the flap regions of the 12X FIV PR more
      closely resemble those of HIV PR, having gained several stabilizing intra-flap
      interactions not present in wild type FIV PR. These findings offer a structural
      explanation for the observed inhibitor/substrate binding properties of the
      chimeric PR.

PMID- 17212811
TI  - Reoperations after first lumbar disc herniation surgery; a special interest on
      residives during a 5-year follow-up.
AB  - BACKGROUND: The overall rate of operations after recurrent lumbar disc herniation
      has been shown to be 3-11%. However, little is known about the rate of residives.
      Thus the aim of this study was to explore the cumulative rates of re-operations
      and especially residive disc herniations at the same side and level as the
      primary disc herniation after first lumbar disc herniation surgery and the
      factors that influence the risk of re-operations over a five year follow-up
      study. METHODS: 166 virgin lumbar disc herniation patients (mean age 42 years,
      57% males) were studied. Data on patients' initial disc operations and type and
      timing of re-operations during the follow-up were collected from patient files.
      Back and leg pain on visual analog scale and employment status were collected by
      questionnaires. RESULTS: The cumulative rate of re-operations for lumbar disc
      herniation was 10.2% (95% Cl 6.0 to 15.1). The rate of residives at initial site
      was 7.4% (95% Cl 3.7 to 11.3) and rate of lumbar disc herniations at other sites
      was 3.1% (95% Cl 0.6 to 6.2). The occurrence of residive lumbar disc herniations
      was evenly distributed across the 5 years. Neither age, gender, preoperative
      symptoms, physical activity nor employment had effect on the probability of re
      operation. CONCLUSION: Seven percent of the lumbar disc patients had a residive
      lumbar disc operation within five years of their first operation. No specific
      factors influencing the risk for re-operation were found.

PMID- 17212812
TI  - Protein kinase C inhibition attenuates vascular ETB receptor upregulation and
      decreases brain damage after cerebral ischemia in rat.
AB  - BACKGROUND: Protein kinase C (PKC) is known to be involved in the pathophysiology
      of experimental cerebral ischemia. We have previously shown that after transient
      middle cerebral artery occlusion, there is an upregulation of endothelin
      receptors in the ipsilateral middle cerebral artery. The present study aimed to
      examine the effect of the PKC inhibitor Ro-32-0432 on endothelin receptor
      upregulation, infarct volume and neurology outcome after middle cerebral artery
      occlusion in rat. RESULTS: At 24 hours after transient middle cerebral artery
      occlusion (MCAO), the contractile endothelin B receptor mediated response and the
      endothelin B receptor protein expression were upregulated in the ipsilateral but
      not the contralateral middle cerebral artery. In Ro-32-0432 treated rats, the
      upregulated endothelin receptor response was attenuated. Furthermore, Ro-32-0432
      treatment decreased the ischemic brain damage significantly and improved
      neurological scores. Immunohistochemistry showed fainter staining of endothelin B
      receptor protein in the smooth muscle cells of the ipsilateral middle cerebral
      artery of Ro-32-0432 treated rats compared to control. CONCLUSION: The results
      suggest that treatment with Ro-32-0432 in ischemic stroke decreases the ischemic
      infarction area, neurological symptoms and associated endothelin B receptor
      upregulation. This provides a new perspective on possible mechanisms of actions
      of PKC inhibition in cerebral ischemia.

PMID- 17212813
TI  - Two non-homologous brain diseases-related genes, SERPINI1 and PDCD10, are tightly
      linked by an asymmetric bidirectional promoter in an evolutionarily conserved
      manner.
AB  - BACKGROUND: Despite of the fact that mammalian genomes are far more spacious than
      prokaryotic genomes, recent nucleotide sequencing data have revealed that many
      mammalian genes are arranged in a head-to-head orientation and separated by a
      small intergenic sequence. Extensive studies on some of these neighboring genes,
      in particular homologous gene pairs, have shown that these genes are often co
      expressed in a symmetric manner and regulated by a shared promoter region. Here
      we report the identification of two non-homologous brain disease-related genes,
      with one coding for a serine protease inhibitor (SERPINI1) and the other for a
      programmed cell death-related gene (PDCD10), being tightly linked together by an
      asymmetric bidirectional promoter in an evolutionarily conserved fashion. This
      asymmetric bidirectional promoter, in cooperation with some cis-acting elements,
      is responsible for the co-regulation of the gene expression pattern as well as
      the tissue specificity of SERPINI1 and PDCD10. RESULTS: While SERPINI1 is
      predominantly expressed in normal brain and down-regulated in brain tumors,
      PDCD10 is ubiquitously expressed in all normal tissues but its gene transcription
      becomes aberrant in different types of cancers. By measuring the luciferase
      activity in various cell lysates, their 851-bp intergenic sequence was shown to
      be capable of driving the reporter gene expression in either direction. A 175-bp
      fragment from nt 1 to 175 in the vicinity of PDCD10 was further determined to
      function as a minimal bidirectional promoter. A critical regulatory fragment,
      from nt 176-473 outside the minimal promoter in the intergenic region, was
      identified to contain a strong repressive element for SERPINI1 and an enhancer
      for PDCD10. These cis-acting elements may exist to help coordinate the expression
      and regulation of the two flanking genes. CONCLUSION: For all non-homologous
      genes that have been described to be closely adjacent in the mammalian genomes,
      the intergenic region of the head-to-head PDCD10-SERPINI1 gene pair provides an
      interesting and informative example of a complex regulatory system that governs
      the expression of both genes not only through an asymmetric bidirectional
      promoter, but also through fine-tuned regulations with some cis-acting elements.

PMID- 17212814
TI  - Ashbya Genome Database 3.0: a cross-species genome and transcriptome browser for
      yeast biologists.
AB  - BACKGROUND: The Ashbya Genome Database (AGD) 3.0 is an innovative cross-species
      genome and transcriptome browser based on release 40 of the Ensembl developer
      environment. DESCRIPTION: AGD 3.0 provides information on 4726 protein-encoding
      loci and 293 non-coding RNA genes present in the genome of the filamentous fungus
      Ashbya gossypii. A synteny viewer depicts the chromosomal location and
      orientation of orthologous genes in the budding yeast Saccharomyces cerevisiae.
      Genome-wide expression profiling data obtained with high-density oligonucleotide
      microarrays (GeneChips) are available for nearly all currently annotated protein
      coding loci in A. gossypii and S. cerevisiae. CONCLUSION: AGD 3.0 hence provides
      yeast- and genome biologists with comprehensive report pages including reliable
      DNA annotation, Gene Ontology terms associated with S. cerevisiae orthologues and
      RNA expression data as well as numerous links to external sources of information.
      The database is accessible at http://agd.vital-it.ch/.

PMID- 17212815
TI  - Amino acid infusion during anesthesia attenuates the surgery induced decline in
      IGF-1 and diminishes the "diabetes of injury".
AB  - BACKGROUND: Surgery, commonly performed after an overnight fast, causes a
      postoperative decline in the anabolic and glucose lowering insulin-like growth
      factor-1 (IGF-1). Clinical fasting studies have exhibited a positive correlation
      between IGF-1 and nitrogen balance during different conditions. A perioperative
      amino acid infusion changes nitrogen balance and might thereby influence serum
      IGF-1. We hypothesized that amino acid infusion would enhance IGF-1 and thereby
      might influence glucose homeostasis after surgery. In this study we examined two
      different regimes of perioperative amino acids infusion. METHODS: 24 females
      scheduled for abdominal hysterectomy were randomized into three groups; Ringer's
      solution infusion throughout anesthesia (Group B), amino acid infusion throughout
      anesthesia (Group C) and amino acid infusion 1 hour before anesthesia and during
      1.5 hrs of surgery (Group D). Six female volunteers, who were not operated, but
      received the same amino acids infusion after fasting, served as controls (Group
      A). Fasting levels of IGF-1, Insulin-like growth factor binding protein-1 (IGFBP
      1), insulin and P-glucose were studied prior to, and four days following,
      operation. Homeostasis model assessment (HOMA) was used as an index of insulin
      resistance. Non-parametric statistical methods were used. RESULTS: During the
      study the Ringer-group exhibited a decrease in IGF-1 and an increase in insulin
      and plasma glucose after surgery. Within the other groups there were no
      significant alterations over time after surgery, with the exception of a
      postoperative decrease in IGF-1 in group D. Group C had higher IGF-1 levels
      compared to group B on all days. Also, group D had higher IGF-1 levels than group
      B on day 2-4. From baseline to the first postoperative day there was a
      significant increase in HOMA and IGFBP-1 in groups B and C. These changes were
      not found in group D, in which insulin, glucose, HOMA and IGFBP-1 did not change.
      Amino acid infusion to the volunteers did not affect any of the variables
      studied. CONCLUSION: Amino acid infusion during surgery attenuates the decrease
      in IGF-1 and diminishes the "diabetes of injury".

PMID- 17212816
TI  - Incidence of low central venous oxygen saturation during unplanned admissions in
      a multidisciplinary intensive care unit: an observational study.
AB  - INTRODUCTION: It has been shown that early central venous oxygen saturation
      (ScvO2)-guided optimization of hemodynamics can improve outcome in septic
      patients. The early ScvO2 profile of other patient groups is unknown. The aim of
      this study was to characterize unplanned admissions in a multidisciplinary
      intensive care unit (ICU) with respect to ScvO2 and outcome. METHODS: Ninety
      eight consecutive unplanned admissions to a multidisciplinary ICU (median age 63
      [range 19 to 83] years, median Simplified Acute Physiology Score [SAPS II] 43
      [range 11 to 92]) with a clinical indication for a central venous catheter were
      included in the study. ScvO2 was assessed at ICU arrival and six hours later but
      was not used to guide treatment. Length of stay in ICU (LOSICU) and in hospital
      (LOShospital) and 28-day mortality were recorded. RESULTS: ScvO2 was 70% +/- 12%
      (mean +/- standard deviation) at admission and 71% +/- 10% six hours later (p =
      0.484). Overall 28-day mortality was 18%, LOSICU was 3 (1 to 28) days, and
      LOShospital was 19 (1 to 28) days. Patients with an ScvO2 of less than 60% at
      admission had higher mortality than patients with an ScvO2 of more than 60% (29%
      versus 17%, p < 0.05). Changes in ScvO2 during the first six hours were not
      predictive of LOSICU, LOShospital, or mortality. CONCLUSION: Low ScvO2 in
      unplanned admissions and high SAPS II are associated with increased mortality.
      Standard ICU treatment increased ScvO2 in patients with a low admission ScvO2,
      but the increase was not associated with LOSICU or LOShospital.

PMID- 17212818
TI  - Acute leukaemoid reaction following cardiac surgery.
AB  - Chronic myelomonocytic leukaemia is an atypical myeloproliferative disorder with
      a natural history of progression to acute myeloid leukaemia, a complex and poorly
      understood response by the bone marrow to stress. Cardiac surgery activates many
      inflammatory cascades and may precipitate a systemic inflammatory response
      syndrome. We present a case of undiagnosed chronic myelomonocytic leukaemia who
      developed rapidly fatal multi-organ dysfunction following cardiac surgery due to
      an acute leukaemoid reaction.

PMID- 17212817
TI  - SIVSM/HIV-2 Vpx proteins promote retroviral escape from a proteasome-dependent
      restriction pathway present in human dendritic cells.
AB  - BACKGROUND: Vpx is a non-structural protein coded by members of the SIVSM/HIV-2
      lineage that is believed to have originated by duplication of the common vpr gene
      present in primate lentiviruses. Vpx is incorporated into virion particles and is
      thus present during the early steps of viral infection, where it is thought to
      drive nuclear import of viral nucleoprotein complexes. We have previously shown
      that Vpx is required for SIVMAC-derived lentiviral vectors (LVs) infection of
      human monocyte-derived dendritic cells (DCs). However, since the requirement for
      Vpx is specific for DCs and not for other non-dividing cell types, this suggests
      that Vpx may play a role other than nuclear import. RESULTS: Here, we show that
      the function of Vpx in the infection of DCs is conserved exclusively within the
      SIVSM/HIV-2 lineage. At a molecular level, Vpx acts by promoting the accumulation
      of full length viral DNA. Furthermore, when supplied in target cells prior to
      infection, Vpx exerts a similar effect following infection of DCs with
      retroviruses as divergent as primate and feline lentiviruses and
      gammaretroviruses. Lastly, the effect of Vpx overlaps with that of the proteasome
      inhibitor MG132 in DCs. CONCLUSION: Overall, our results support the notion that
      Vpx modifies the intracellular milieu of target DCs to facilitate lentiviral
      infection. The data suggest that this is achieved by promoting viral escape from
      a proteasome-dependent pathway especially detrimental to viral infection in DCs.

PMID- 17212819
TI  - Phylogenetic tree information aids supervised learning for predicting protein
      protein interaction based on distance matrices.
AB  - BACKGROUND: Protein-protein interactions are critical for cellular functions.
      Recently developed computational approaches for predicting protein-protein
      interactions utilize co-evolutionary information of the interacting partners,
      e.g., correlations between distance matrices, where each matrix stores the
      pairwise distances between a protein and its orthologs from a group of reference
      genomes. RESULTS: We proposed a novel, simple method to account for some of the
      intra-matrix correlations in improving the prediction accuracy. Specifically, the
      phylogenetic species tree of the reference genomes is used as a guide tree for
      hierarchical clustering of the orthologous proteins. The distances between these
      clusters, derived from the original pairwise distance matrix using the Neighbor
      Joining algorithm, form intermediate distance matrices, which are then
      transformed and concatenated into a super phylogenetic vector. A support vector
      machine is trained and tested on pairs of proteins, represented as super
      phylogenetic vectors, whose interactions are known. The performance, measured as
      ROC score in cross validation experiments, shows significant improvement of our
      method (ROC score 0.8446) over that of using Pearson correlations (0.6587).
      CONCLUSION: We have shown that the phylogenetic tree can be used as a guide to
      extract intra-matrix correlations in the distance matrices of orthologous
      proteins, where these correlations are represented as intermediate distance
      matrices of the ancestral orthologous proteins. Both the unsupervised and
      supervised learning paradigms benefit from the explicit inclusion of these
      intermediate distance matrices, and particularly so in the latter case, which
      offers a better balance between sensitivity and specificity in the prediction of
      protein-protein interactions.

PMID- 17212820
TI  - Pneumatized superior turbinate as a cause of headache.
AB  - BACKGROUND: A pneumatized superior turbinate is a rare cause of headache. Nasal
      endoscopy alone, does not provide us with adequate information for this
      inaccessible area of the superior nasal cavity. A coronal computed tomography
      (CT) must be obtained to confirm the diagnosis. CASE PRESENTATION: We present a
      40-year-old female with migraine-type headache and nasal obstruction. Nasal
      endoscopy revealed a mild septal deviation, a right middle concha bullosa and a
      paradoxically curved middle turbinate on the left side. Coronal CT-scan showed
      also the presence of a superior concha bullosa on the left, which was in close
      contact with the nasal septum. The patient underwent septoplasty and bilateral
      endoscopic sinus surgery, including partial removal of both the pneumatized
      middle turbinates in conjunction with gentle lateralization and resection of the
      lower half of the left superior turbinate. Prompt relief from headache and nasal
      symptoms was obtained. CONCLUSION: Pneumatized superior concha causing migrainous
      headache is a rare finding. Endoscopic surgery may provide permanent relief of
      symptoms.

PMID- 17212821
TI  - Differential diagnosis of laryngeal spindle cell carcinoma and inflammatory
      myofibroblastic tumor--report of two cases with similar morphology.
AB  - BACKGROUND: Spindle cell tumors of the larynx are rare. In some cases, the
      dignity is difficult to determine. We report two cases of laryngeal spindle cell
      tumors. CASE PRESENTATION: Case 1 is a spindle cell carcinoma (SPC) in a 55 year
      old male patient and case 2 an inflammatory myofibroblastic tumor (IMT) in a 34
      year-old female patient. A comprehensive morphological and immunohistochemical
      analysis was done. Both tumors arose at the vocal folds. Magnified laryngoscopy
      showed polypoid tumors. After resection, conventional histological investigation
      revealed spindle cell lesions with similar morphology. We found ulceration, mild
      atypia, and myxoid stroma. Before immunohistochemistry, the dignity was
      uncertain. Immunohistochemical investigations led to diagnosis of two distinct
      tumors with different biological behaviour. Both expressed vimentin. Furthermore,
      the SPC was positive for pan-cytokeratin AE1/3, CK5/6, and smooth-muscle actin,
      whereas the IMT reacted with antibodies against ALK-1, and EMA. The proliferation
      (Ki67) was up to 80% in SPC and 10% in IMT. Other stainings with antibodies
      against p53, p21, Cyclin D1, or Rb did not result in additional information.
      After resection, the patient with SPC is free of disease for seven months. The
      IMT recurred three months after first surgery, but no relapses were found eight
      months after resurgery. CONCLUSION: Differential diagnosis can be difficult
      without immunohistochemistry. Therefore, a comprehensive morphological and
      immunohistochemical analysis is necessary, but markers of cell cycle (apart from
      the assessment of proliferation) do not help.

PMID- 17212822
TI  - 8-epi-Salvinorin B: crystal structure and affinity at the kappa opioid receptor.
AB  - There have been many reports of epimerization of salvinorins at C-8 under basic
      conditions, but little evidence has been presented to establish the structure of
      these compounds. We report here the first crystal structure of an 8-epi
      salvinorin or derivative: the title compound, 2b. The lactone adopts a boat
      conformation with the furan equatorial. Several lines of evidence suggest that
      epimerization proceeds via enolization of the lactone rather than a previously
      proposed indirect mechanism. Consistent with the general trend in related
      compounds, the title compound showed lower affinity at the kappa opioid receptor
      than the natural epimer salvinorin B (2a). The related 8-epi-acid 4b showed no
      affinity.

PMID- 17212823
TI  - Prospects of micromass culture technology in tissue engineering.
AB  - Tissue engineering of bone and cartilage tissue for subsequent implantation is of
      growing interest in cranio- and maxillofacial surgery. Commonly it is performed
      by using cells coaxed with scaffolds. Recently, there is a controversy concerning
      the use of artificial scaffolds compared to the use of a natural matrix.
      Therefore, new approaches called micromass technology have been invented to
      overcome these problems by avoiding the need for scaffolds. Technically, cells
      are dissociated and the dispersed cells are then reaggregated into cellular
      spheres. The micromass technology approach enables investigators to follow tissue
      formation from single cell sources to organised spheres in a controlled
      environment. Thus, the inherent fundamentals of tissue engineering are better
      revealed. Additionally, as the newly formed tissue is devoid of an artificial
      material, it resembles more closely the in vivo situation. The purpose of this
      review is to provide an insight into the fundamentals and the technique of
      micromass cell culture used to study bone tissue engineering.

PMID- 17212824
TI  - Progression of renal cell carcinoma is inhibited by genistein and radiation in an
      orthotopic model.
AB  - BACKGROUND: We have previously reported the potentiation of radiotherapy by the
      soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro
      and orthotopic prostate tumor models in vivo. However, when genistein was used as
      single therapy in animal models, it promoted metastasis to regional para-aortic
      lymph nodes. To clarify whether these intriguing adverse effects of genistein are
      intrinsic to the orthotopic prostate tumor model, or these results could also be
      recapitulated in another model, we used the orthotopic metastatic KCI-18 renal
      cell carcinoma (RCC) model established in our laboratory. METHODS: The KCI-18 RCC
      cell line was generated from a patient with papillary renal cell carcinoma.
      Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo
      kidney passages in nude mice, we have established a reliable and predictable
      metastatic RCC tumor model. Mice bearing established kidney tumors were treated
      with genistein combined with kidney tumor irradiation. The effect of the therapy
      was assessed on the primary tumor and metastases to various organs. RESULTS: In
      this experimental model, the karyotype and histological characteristics of the
      human primary tumor are preserved. Tumor cells metastasize from the primary renal
      tumor to the lungs, liver and mesentery mimicking the progression of RCC in
      humans. Treatment of established kidney tumors with genistein demonstrated a
      tendency to stimulate the growth of the primary kidney tumor and increase the
      incidence of metastasis to the mesentery lining the bowel. In contrast, when
      given in conjunction with kidney tumor irradiation, genistein significantly
      inhibited the growth and progression of established kidney tumors. These findings
      confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model
      as previously shown in orthotopic models of prostate cancer. CONCLUSION: Our
      studies in both RCC and prostate tumor models demonstrate that the combination of
      genistein with primary tumor irradiation is a more effective and safer
      therapeutic approach as the tumor growth and progression are inhibited both in
      the primary and metastatic sites.

PMID- 17212825
TI  - Low-cost rapid detection of rifampicin resistant tuberculosis using bacteriophage
      in Kampala, Uganda.
AB  - BACKGROUND: Resistance to anti-tuberculosis drugs is a serious public health
      problem. Multi-drug resistant tuberculosis (MDR-TB), defined as resistance to at
      least rifampicin and isoniazid, has been reported in all regions of the world.
      Current phenotypic methods of assessing drug susceptibility of M. tuberculosis
      are slow. Rapid molecular methods to detect resistance to rifampicin have been
      developed but they are not affordable in some high prevalence countries such as
      those in sub Saharan Africa. A simple multi-well plate assay using
      mycobacteriophage D29 has been developed to test M. tuberculosis isolates for
      resistance to rifampicin. The purpose of this study was to investigate the
      performance of this technology in Kampala, Uganda. METHODS: In a blinded study
      149 M. tuberculosis isolates were tested for resistance to rifampicin by the
      phage assay and results compared to those from routine phenotypic testing in
      BACTEC 460. Three concentrations of drug were used 2, 4 and 10 microg/ml.
      Isolates found resistant by either assay were subjected to sequence analysis of a
      81 bp fragment of the rpoB gene to identify mutations predictive of resistance.
      Four isolates with discrepant phage and BACTEC results were tested in a second
      phenotypic assay to determine minimal inhibitory concentrations. RESULTS: Initial
      analysis suggested a sensitivity and specificity of 100% and 96.5% respectively
      for the phage assay used at 4 and 10 microg/ml when compared to the BACTEC 460.
      However, further analysis revealed 4 false negative results from the BACTEC 460
      and the phage assay proved the more sensitive and specific of the two tests. Of
      the 39 isolates found resistant by the phage assay 38 (97.4%) were found to have
      mutations predictive of resistance in the 81 bp region of the rpoB gene. When
      used at 2 mug/ml false resistant results were observed from the phage assay. The
      cost of reagents for testing each isolate was estimated to be 1.3 US dollars when
      testing a batch of 20 isolates on a single 96 well plate. Results were obtained
      in 48 hours. CONCLUSION: The phage assay can be used for screening of isolates
      for resistance to rifampicin, with high sensitivity and specificity in Uganda.
      The test may be useful in poorly resourced laboratories as a rapid screen to
      differentiate between rifampicin susceptible and potential MDR-TB cases.

PMID- 17212826
TI  - TAMGeS: a Three-array Method for Genotyping of SNPs by a dual-colour approach.
AB  - BACKGROUND: Many of the most effective high-throughput protocols for SNP
      genotyping employ microarrays. Genotypes are assessed by comparing the signal
      intensities that derive from the hybridization of different allele-specific
      probes labelled either by using four fluorescent dyes, one for each base, or by
      using only two dyes and investigating the polymorphic alleles two by two on
      separate arrays. The employment of only two dyes makes it possible to use a dual
      laser scanner, which has the advantage of being present in every microarray
      laboratory. However, this protocol may present some drawbacks. To infer all the
      six possible genotypes it is necessary to compare signals from two arrays, but
      this comparison not always is successful. A number of systematic errors in the
      experimental protocol, in fact, may differently affect signal intensities on
      separate arrays. Here we present TAMGeS (Three-Array Method for Genotyping of
      SNPs), an exhaustive method for SNP genotyping through SBE (Single Base
      Extension) and dual-colour microarrays, which makes the comparison of signals on
      distinct arrays reliable by using a third array and a data handling method for
      signal normalization based on bilinear regression theory. RESULTS: We tested the
      effectiveness of the proposed method by evaluating the results obtained from the
      direct comparison of the two arrays or by applying TAMGeS, both on experimental
      and synthetic data. With synthetic data, TAMGeS reduced the frequency of errors
      by an order of magnitude, when the incidence of systematic errors was not
      negligible. With the experimental data, produced by genotyping 25 SNPs in 437
      subjects, TAMGeS reduced the percentage of missing genotypes from 54% (Two-Array
      Method) to 14.5%. Allelic and genotypic call rates were 99.3% and 99.5%,
      respectively. The normalization procedure takes into account also systematic
      errors, which can be generated by a time-delayed assay, thus making the protocol
      more flexible. CONCLUSION: TAMGeS represents an innovative method, which proved
      to be very effective in producing reliable SNP genotyping data by dual-colour
      microarrays. The requirement of a third array is well balanced by the strong
      enhancement in data quality and by the greater flexibility of the experimental
      protocol.

PMID- 17212827
TI  - Large-scale mapping of mutations affecting zebrafish development.
AB  - BACKGROUND: Large-scale mutagenesis screens in the zebrafish employing the
      mutagen ENU have isolated several hundred mutant loci that represent putative
      developmental control genes. In order to realize the potential of such screens,
      systematic genetic mapping of the mutations is necessary. Here we report on a
      large-scale effort to map the mutations generated in mutagenesis screening at the
      Max Planck Institute for Developmental Biology by genome scanning with
      microsatellite markers. RESULTS: We have selected a set of microsatellite markers
      and developed methods and scoring criteria suitable for efficient, high
      throughput genome scanning. We have used these methods to successfully obtain a
      rough map position for 319 mutant loci from the Tubingen I mutagenesis screen and
      subsequent screening of the mutant collection. For 277 of these the corresponding
      gene is not yet identified. Mapping was successful for 80 % of the tested loci.
      By comparing 21 mutation and gene positions of cloned mutations we have validated
      the correctness of our linkage group assignments and estimated the standard error
      of our map positions to be approximately 6 cM. CONCLUSION: By obtaining rough map
      positions for over 300 zebrafish loci with developmental phenotypes, we have
      generated a dataset that will be useful not only for cloning of the affected
      genes, but also to suggest allelism of mutations with similar phenotypes that
      will be identified in future screens. Furthermore this work validates the
      usefulness of our methodology for rapid, systematic and inexpensive
      microsatellite mapping of zebrafish mutations.

PMID- 17212828
TI  - eQTL Viewer: visualizing how sequence variation affects genome-wide
      transcription.
AB  - BACKGROUND: Expression Quantitative Trait Locus (eQTL) mapping methods have been
      used to identify the genetic basis of gene expression variations. To map eQTL,
      thousands of expression profiles are related with sequence polymorphisms across
      the genome through their correlated variations. These eQTL distribute in many
      chromosomal regions, each of which can include many genes. The large number of
      mapping results produced makes it difficult to consider simultaneously the
      relationships between multiple genomic regions and multiple expressional
      profiles. There is a need for informative bioinformatics tools to assist the
      visualization and interpretation of these mapping results. RESULTS: We have
      developed a web-based tool, called eQTL Viewer, to visualize the relationships
      between the expression trait genes and the candidate genes in the eQTL regions
      using Scalable Vector Graphics. The plot generated by eQTL Viewer has the
      capacity to display mapping results with high resolutions at a variety of scales,
      and superimpose biological annotations onto the mapping results dynamically.
      CONCLUSION: Our tool provides an efficient and intuitive way for biologists to
      explore transcriptional regulation patterns, and to generate hypotheses on the
      genetic basis of transcriptional regulations.

PMID- 17212829
TI  - Attainment of clinical performance targets and improvement in clinical outcomes
      and resource use in hemodialysis care: a prospective cohort study.
AB  - BACKGROUND: Clinical performance targets are intended to improve patient outcomes
      in chronic disease through quality improvement, but evidence of an association
      between multiple target attainment and patient outcomes in routine clinical
      practice is often lacking. METHODS: In a national prospective cohort study (ESRD
      Quality, or EQUAL), we examined whether attainment of multiple targets in 668
      incident hemodialysis patients from 74 U.S. not-for-profit dialysis clinics was
      associated with better outcomes. We measured whether the following accepted
      clinical performance targets were met at 6 months after study enrollment: albumin
      (> or =4.0 g/dl), hemoglobin (> or =11 g/dl), calcium-phosphate product (<55
      mg2/dl2), dialysis dose (Kt/V> or =1.2), and vascular access type (fistula).
      Outcomes included mortality, hospital admissions, hospital days, and hospital
      costs. RESULTS: Attainment of each of the five targets was associated
      individually with better outcomes; e.g., patients who attained the albumin target
      had decreased mortality [relative hazard (RH) = 0.55, 95% confidence interval
      (CI), 0.41-0.75], hospital admissions [incidence rate ratio (IRR) = 0.67, 95% CI,
      0.62-0.73], hospital days (IRR = 0.61, 95% CI, 0.58-0.63), and hospital costs
      (average annual cost reduction = 3,282 dollars, P = 0.002), relative to those who
      did not. Increasing numbers of targets attained were also associated, in a graded
      fashion, with decreased mortality (P = 0.030), fewer hospital admissions and days
      (P < 0.001 for both), and lower costs (P = 0.029); these trends remained
      statistically significant for all outcomes after adjustment (P < 0.001), except
      cost, which was marginally significant (P = 0.052). CONCLUSION: Attainment of
      more clinical performance targets, regardless of which targets, was strongly
      associated with decreased mortality, hospital admissions, and resource use in
      hemodialysis patients.

PMID- 17212831
TI  - A stochastic model for circadian rhythms from coupled ultradian oscillators.
AB  - BACKGROUND: Circadian rhythms with varying components exist in organisms ranging
      from humans to cyanobacteria. A simple evolutionarily plausible mechanism for the
      origin of such a variety of circadian oscillators, proposed in earlier work,
      involves the non-disruptive coupling of pre-existing ultradian transcriptional
      translational oscillators (TTOs), producing "beats," in individual cells.
      However, like other TTO models of circadian rhythms, it is important to establish
      that the inherent stochasticity of the protein binding and unbinding does not
      invalidate the finding of clear oscillations with circadian period. RESULTS: The
      TTOs of our model are described in two versions: 1) a version in which the
      activation or inhibition of genes is regulated stochastically, where the
      'unoccupied" (or "free") time of the site under consideration depends on the
      concentration of a protein complex produced by another site, and 2) a
      deterministic, "time-averaged" version in which the switching between the "free"
      and "occupied" states of the sites occurs so rapidly that the stochastic effects
      average out. The second case is proved to emerge from the first in a
      mathematically rigorous way. Numerical results for both scenarios are presented
      and compared. CONCLUSION: Our model proves to be robust to the stochasticity of
      protein binding/unbinding at experimentally determined rates and even at rates
      several orders of magnitude slower. We have not only confirmed this by numerical
      simulation, but have shown in a mathematically rigorous way that the time
      averaged deterministic system is indeed the fast-binding-rate limit of the full
      stochastic model.

PMID- 17212830
TI  - A multi-treatment experimental system to examine photosynthetic differentiation
      in the maize leaf.
AB  - BACKGROUND: The establishment of C4 photosynthesis in maize is associated with
      differential accumulation of gene transcripts and proteins between bundle sheath
      and mesophyll photosynthetic cell types. We have physically separated
      photosynthetic cell types in the leaf blade to characterize differences in gene
      expression by microarray analysis. Additional control treatments were used to
      account for transcriptional changes induced by cell preparation treatments. To
      analyse these data, we have developed a statistical model to compare gene
      expression values derived from multiple, partially confounded, treatment groups.
      RESULTS: Differential gene expression in the leaves of wild-type maize seedlings
      was characterized using the latest release of a maize long-oligonucleotide
      microarray produced by the Maize Array Project consortium. The complete data set
      is available through the project web site. Data is also available at the NCBI GEO
      website, series record GSE3890. Data was analysed with and without consideration
      of cell preparation associated stress. CONCLUSION: Empirical comparison of the
      two analyses suggested that consideration of stress helped to reduce the false
      identification of stress responsive transcripts as cell-type enriched. Using our
      model including a stress term, we identified 8% of features as differentially
      expressed between bundle sheath and mesophyll cell types under control of false
      discovery rate of 5%. An estimate of the overall proportion of differentially
      accumulating transcripts (1-pi0) suggested that as many as 18% of the genes may
      be differentially expressed between B and M. The analytical model presented here
      is generally applicable to gene expression data and demonstrates the use of
      statistical elimination of confounding effects such as stress in the context of
      microarray analysis. We discuss the implications of the high degree of
      differential transcript accumulation observed with regard to both the
      establishment and engineering of the C4 syndrome.

PMID- 17212832
TI  - Counting colonies of clonogenic assays by using densitometric software.
AB  - Clonogenic assays are a useful tool to test whether a given cancer therapy can
      reduce the clonogenic survival of tumour cells. A colony is defined as a cluster
      of at least 50 cells which can often only be determined microscopically. The
      process of counting colonies is very extensive work and so we developed software
      that is able to count the colonies automatically from scanned flasks. This
      software is made freely available by us with a detailed description how to use
      and install the necessary features.

PMID- 17212834
TI  - Identification of putative cis-regulatory elements in Cryptosporidium parvum by
      de novo pattern finding.
AB  - BACKGROUND: Cryptosporidium parvum is a unicellular eukaryote in the phylum
      Apicomplexa. It is an obligate intracellular parasite that causes diarrhea and is
      a significant AIDS-related pathogen. Cryptosporidium parvum is not amenable to
      long-term laboratory cultivation or classical molecular genetic analysis. The
      parasite exhibits a complex life cycle, a broad host range, and fundamental
      mechanisms of gene regulation remain unknown. We have used data from the recently
      sequenced genome of this organism to uncover clues about gene regulation in C.
      parvum. We have applied two pattern finding algorithms MEME and AlignACE to
      identify conserved, over-represented motifs in the 5' upstream regions of genes
      in C. parvum. To support our findings, we have established comparative real-time 
      PCR expression profiles for the groups of genes examined computationally.
      RESULTS: We find that groups of genes that share a function or belong to a common
      pathway share upstream motifs. Different motifs are conserved upstream of
      different groups of genes. Comparative real-time PCR studies show co-expression
      of genes within each group (in sub-sets) during the life cycle of the parasite,
      suggesting co-regulation of these genes may be driven by the use of conserved
      upstream motifs. CONCLUSION: This is one of the first attempts to characterize
      cis-regulatory elements in the absence of any previously characterized elements
      and with very limited expression data (seven genes only). Using de novo pattern
      finding algorithms, we have identified specific DNA motifs that are conserved
      upstream of genes belonging to the same metabolic pathway or gene family. We have
      demonstrated the co-expression of these genes (often in subsets) using
      comparative real-time-PCR experiments thus establishing evidence for these
      conserved motifs as putative cis-regulatory elements. Given the lack of prior
      information concerning expression patterns and organization of promoters in C.
      parvum we present one of the first investigations of gene regulation in this
      important human pathogen.

PMID- 17212835
TI  - Least-squares methods for identifying biochemical regulatory networks from noisy
      measurements.
AB  - BACKGROUND: We consider the problem of identifying the dynamic interactions in
      biochemical networks from noisy experimental data. Typically, approaches for
      solving this problem make use of an estimation algorithm such as the well-known
      linear Least-Squares (LS) estimation technique. We demonstrate that when time
      series measurements are corrupted by white noise and/or drift noise, more
      accurate and reliable identification of network interactions can be achieved by
      employing an estimation algorithm known as Constrained Total Least Squares
      (CTLS). The Total Least Squares (TLS) technique is a generalised least squares
      method to solve an overdetermined set of equations whose coefficients are noisy.
      The CTLS is a natural extension of TLS to the case where the noise components of
      the coefficients are correlated, as is usually the case with time-series
      measurements of concentrations and expression profiles in gene networks. RESULTS:
      The superior performance of the CTLS method in identifying network interactions
      is demonstrated on three examples: a genetic network containing four genes, a
      network describing p53 activity and mdm2 messenger RNA interactions, and a
      recently proposed kinetic model for interleukin (IL)-6 and (IL)-12b messenger RNA
      expression as a function of ATF3 and NF-kappaB promoter binding. For the first
      example, the CTLS significantly reduces the errors in the estimation of the
      Jacobian for the gene network. For the second, the CTLS reduces the errors from
      the measurements that are corrupted by white noise and the effect of neglected
      kinetics. For the third, it allows the correct identification, from noisy data,
      of the negative regulation of (IL)-6 and (IL)-12b by ATF3. CONCLUSION: The
      significant improvements in performance demonstrated by the CTLS method under the
      wide range of conditions tested here, including different levels and types of
      measurement noise and different numbers of data points, suggests that its
      application will enable more accurate and reliable identification and modelling
      of biochemical networks.

PMID- 17212833
TI  - State of the art: noninvasive imaging and management of neurovascular trauma.
AB  - Neurotrauma represents a significant public health problem, accounting for a
      significant proportion of the morbidity and mortality associated with all
      traumatic injuries. Both blunt and penetrating injuries to cervicocerebral
      vessels are significant and are likely more common than previously recognized.
      Imaging of such injuries is an important component in the evaluation of
      individuals presenting with such potential injuries, made all the more important
      since many of the vascular injuries are clinically silent. Management of
      injuries, particularly those caused by blunt trauma, is constantly evolving. This
      article addresses the current state of imaging and treatment of such injuries.

PMID- 17212836
TI  - Measuring dietary diversity in rural Burkina Faso: comparison of a 1-day and a 3
      day dietary recall.
AB  - OBJECTIVES: To compare dietary diversity scores measured over a 1-day and a 3-day
      period, and to assess their relationships with socio-economic characteristics and
      the nutritional status of rural African women. DESIGN: A qualitative dietary
      recall allowed calculation of a dietary diversity score (DDS; number of food
      groups consumed out of a total of nine). Body mass index (BMI) and body fat
      percentage (BFP) were used to assess the nutritional status of women. SETTING AND
      SUBJECTS: A representative sample of 550 mothers in north-east Burkina Faso.
      RESULTS: The DDS increased from 3.5 to 4.4 when calculated from a 1-day or a 3
      day recall (P < 0.0001), although for the latter the DDS was affected by memory
      bias. The DDS calculated from a 1-day recall was higher when a market day
      occurred during the recall period. Both scores were linked to the
      sociodemographic and economic characteristics of the women. Women in the lowest
      DDS tertile calculated from the 1-day recall had a mean BMI of 20.5 kg m-(2) and
      17.7% of them were underweight, versus 21.6 kg m (-2) and 3.5% for those in the
      highest tertile (P = 0.0003 and 0.0007, respectively). The DDS calculated from
      the 1-day recall was also linked to mean BFP; all these links remained
      significant after adjustment for confounders. For the 3-day period, no such
      relationships were found to be significant after adjustment. CONCLUSION: The DDS
      calculated from a 1-day dietary recall was sufficient to predict the women's
      nutritional status. In such a context attention should be paid to market days.

PMID- 17212837
TI  - Paternal smoking is associated with increased risk of child malnutrition among
      poor urban families in Indonesia.
AB  - OBJECTIVE: Paternal smoking is highly prevalent in Asia, and tobacco may account
      for a large proportion of household expenditures among poor families. We sought
      to characterise the relationship between paternal smoking, child malnutrition and
      food expenditures. DESIGN: Data on smoking, household expenditures and child
      malnutrition were examined in a stratified multistage cluster sample of
      households in the Indonesia nutrition surveillance system. Main outcome measures
      were child wasting (weight-for-height Z-score < - 2), underweight (weight-for-age
      Z-score < - 2) and stunting (height-for-age Z-score < - 2), and severe wasting,
      underweight and stunting (defined by respective Z-scores < - 3). SETTING: In
      total, 175,583 households from urban slum areas in Indonesia. SUBJECTS: Children
      0-59 months of age. RESULTS: The prevalence of paternal smoking was 73.8%. After
      adjusting for child gender and age, maternal age and education, and weekly per
      capita household expenditures, paternal smoking was associated with child
      stunting (odds ratio (OR) = 1.11, 95% confidence interval (CI) 1.08-1.14, P <
      0.0001), severe wasting (OR = 1.17, 95% CI 1.03-1.33, P = 0.018) and severe
      stunting (OR = 1.09, 95% CI 1.04-1.15, P < 0.001). In households where the father
      was a smoker, tobacco accounted for 22% of weekly per capita household
      expenditures, with less money spent on food compared with households in which the
      father was a non-smoker. CONCLUSIONS: Among poor families in urban slum areas of
      Indonesia, paternal smoking diverts household money from food to tobacco and
      exacerbates child malnutrition.

PMID- 17212838
TI  - Fast food for family meals: relationships with parent and adolescent food intake,
      home food availability and weight status.
AB  - OBJECTIVE: The purpose of the present study was to examine the prevalence of fast
      food purchases for family meals and the associations with sociodemographic
      variables, dietary intake, home food environment, and weight status in
      adolescents and their parents. DESIGN: This study is a cross-sectional evaluation
      of parent interviews and adolescent surveys from Project EAT (Eating Among
      Teens). SUBJECTS: Subjects included 902 middle-school and high-school adolescents
      (53% female, 47% male) and their parents (89% female, 11% male). The adolescent
      population was ethnically diverse: 29% white, 24% black, 21% Asian American, 14%
      Hispanic and 12% other. RESULTS: Results showed that parents who reported
      purchasing fast food for family meals at least 3 times per week were
      significantly more likely than parents who reported purchasing fewer fast-food
      family meals to report the availability of soda pop and chips in the home.
      Adolescents in homes with fewer than 3 fast-food family meals per week were
      significantly more likely than adolescents in homes with more fast-food family
      meals to report having vegetables and milk served with meals at home. Fast-food
      purchases for family meals were positively associated with the intake of fast
      foods and salty snack foods for both parents and adolescents; and weight status
      among parents. Fast-food purchases for family meals were negatively associated
      with parental vegetable intake. CONCLUSIONS: Fast-food purchases may be helpful
      for busy families, but families need to be educated on the effects of fast food
      for family meals and how to choose healthier, convenient family meals.

PMID- 17212839
TI  - Impact of parental education and income inequality on children's food intake.
AB  - OBJECTIVE: To analyse the association between socio-economic indicators and diet
      among 2-year-old children, by assessing the independent contribution of parental
      education and equivalent income to food intake. DESIGN: The analysis was based on
      data from a prospective birth cohort study. Information on diet was obtained
      using a semi-quantitative food-frequency questionnaire. Low and high intake of
      food was defined according to the lowest and the highest quintile of food
      consumption frequency, respectively. SETTING: Four German cities (Munich,
      Leipzig, Wesel, Bad Honnef), 1999-2001. Subjects Subjects were 2637 children at
      the age of 2 years, whose parents completed questionnaires gathering information
      on lifestyle factors, including parental socio-economic status, household
      consumption frequencies and children's diet. RESULTS: Both low parental education
      and low equivalent income were associated with a low intake of fresh fruit,
      cooked vegetables and olive oil, and a high intake of canned vegetables or fruit,
      margarine, mayonnaise and processed salad dressing in children. Children with a
      low intake of milk and cream, and a high intake of hardened vegetable fat, more
      likely had parents with lower education. Low butter intake was associated with
      low equivalent income only. CONCLUSIONS: These findings may be helpful for future
      intervention programmes with more targeted policies aiming at an improvement of
      children's diets.

PMID- 17212840
TI  - Fruit and vegetable consumption and self-reported functional health in men and
      women in the European Prospective Investigation into Cancer-Norfolk (EPIC
      Norfolk): a population-based cross-sectional study.
AB  - OBJECTIVES: To investigate the association between fruit and vegetable
      consumption and self-reported physical and mental functional health measured by
      an anglicised short-form 36-item questionnaire (UK SF-36). DESIGN: Population
      based cross-sectional study. SETTING: General community in Norfolk, UK. SUBJECTS:
      A total of 16,792 men and women aged 40-79 years recruited from general practice
      population registers as part of the European Prospective Investigation into
      Cancer (EPIC)-Norfolk study, who completed food-frequency questionnaires in 1993
      1997 and Health and Life Experiences Questionnaires 18 months later, were
      enrolled in the study. RESULTS: Mean SF-36 physical component summary scores
      increased significantly with increasing total fruit and vegetable consumption in
      both men and women (P < 0.0001 for trend). Men and women in the top quartile of
      consumption compared with the bottom quartile had a significantly higher
      likelihood of reporting good physical health (defined as a score > or = 55); odds
      ratio (OR) 1.30, 95% confidence interval (CI) 1.11-1.53 for men and OR 1.28, 95%
      CI 1.11-1.48 for women, after controlling for age, body mass index, smoking,
      education, social class, prevalent illness and total energy intake. Exclusion of
      current smokers and people with prevalent illness did not alter the associations.
      CONCLUSION: Higher fruit and vegetable consumption is associated with better self
      reported physical functional health within a general population. Increasing daily
      intake by two portions of fruit and vegetables was associated with an 11% higher
      likelihood of good functional health. Since the current average consumption of
      fruit and vegetables in the UK is about three portions, the recommended 'five a
      day' strategy may have additional benefit for functional as well as other health
      outcomes in the population.

PMID- 17212841
TI  - Delivering multidisciplinary public health in action - the Cardiff food strategy
      case study.
AB  - BACKGROUND: There is an increasing awareness that the provision of healthy food
      relies on the co-ordinated efforts of a number of diverse disciplines, not merely
      those traditionally linked with food. This paper documents the development of a
      food and health strategy, commissioned by the health alliance for the city of
      Cardiff, and focuses on the areas of sustainability, education and training as
      well as nutrition, food provision and food safety. OBJECTIVE: The aim of the
      strategy was to increase the uptake of a healthy, safe and sustainable diet for
      all those living in Cardiff. METHOD: The methodology included a rapid appraisal
      of food initiatives operating within the city, establishing a food and health
      strategy working group and the production of strategy documentation. Multi-agency
      collaboration and consultation were key components of the approach. RESULTS: As
      the strategy developed, seven action areas became apparent, including education
      and training, public sector procurement and rewarding excellence. These action
      areas were incorporated into seven 'action tables', which constitute the core of
      the strategy. The food and health strategy document was ratified by the Local
      Health Alliance board in August 2004. But, far greater benefits were realised as
      a consequence of setting up the strategy working group. Long before the document
      was written, the strategy process was operating as 'multidisciplinary public
      health in action'. CONCLUSION: The network that comprised the food and health
      strategy working group was already able to commence delivery of a more integrated
      approach to food and health within Cardiff.

PMID- 17212842
TI  - The impact of food supplementation on infant weight gain in rural Bangladesh; an
      assessment of the Bangladesh Integrated Nutritional Program (BINP).
AB  - OBJECTIVES: To examine the efficiency of the Bangladesh Integrated Nutritional
      Program (BINP) in identifying which infants should be supplemented, whether full
      supplementation was given for the stipulated period of time, and whether the
      correct exit criteria from the supplementation programme were used. To test
      whether targeted food supplementation of infants between 6-12 months of age
      resulted in enhanced weight gain. SETTING: Mallickbari Union, Bhaluka, a rural
      area located about 100 km north of Dhaka, Bangladesh. PARTICIPANTS: Five hundred
      and twenty-six infants followed for 6 to 12 months. RESULTS: Of the 526 infants
      studied, 368 should have received supplementation based on BINP criteria but only
      111 infants (30%) did so, while a further 13% were incorrectly given
      supplementation. So in total over half (52.8%) of the sample was incorrectly
      identified for supplementation. In addition, less than a quarter of the infants
      received the full 90 days of supplementation and close to half of the infants
      exited the programme without the requisite weight gain. Infants were assigned to
      one of four groups: correctly supplemented, correctly non-supplemented,
      incorrectly supplemented or incorrectly non-supplemented. This classification
      provided natural controls; the correctly supplemented infants versus the
      incorrectly non-supplemented infants, and the correctly non-supplemented infants
      versus the incorrectly supplemented infants. There were no significant
      differences in weight gain between the correctly supplemented group and the
      incorrectly non-supplemented group or between the correctly non-supplemented and
      the incorrectly supplemented groups, nor was there any evidence of growth
      faltering in the incorrectly non-supplemented group. CONCLUSIONS: This study
      found serious programmatic deficiencies - inability to identify growth faltering
      in infants, failure to supplement for the full time period and incorrect exit
      procedures. There was no evidence that food supplementation had any impact on
      improving infant weight gain.

PMID- 17212843
TI  - The role of breakfast in nutrient intake of urban schoolchildren.
AB  - OBJECTIVES: To ascertain the breakfast habits of 10-15-year-old schoolchildren
      and to assess the quality of this meal as well as its relationship to the food
      consumption pattern for the full day. DESIGN: Cross-sectional survey. SUBJECTS
      AND SETTING: Eight hundred and two schoolchildren, boys and girls, aged 10-15
      years, belonging to different urban schools located in Secunderabad, Andhra
      Pradesh, India. METHOD: The breakfast eating patterns of the children were
      studied and their impact on growth was assessed, using dietary recalls and
      anthropometric measurements. RESULTS: Only 42.8% of the children ate breakfast
      regularly. Over half of the children skipped breakfast, ranging from daily to
      once in two weeks. The energy and protein composition of breakfasts eaten by the
      children indicated that those who did not skip breakfast met one-quarter to one
      third of their total daily energy and protein requirements. Mean nutrient intakes
      calculated from 24-hour recalls revealed that the children's diets were
      inadequate compared with the recommended values for energy and protein. The
      inadequate energy intake was reflected in a high incidence of malnutrition in
      both boys and girls; 40.3% of the boys and 32.1% of the girls studied were found
      to be underweight. Protein intake was also inadequate among boys and girls,
      although a higher percentage of children met their protein requirements.
      CONCLUSIONS: Over half of the schoolchildren studied skipped breakfast
      frequently, the main reason being getting up late. Children who consumed
      breakfast had higher daily intakes of energy and protein than children who
      skipped breakfast. These data confirm the importance of breakfast to overall
      dietary quality and adequacy in school-aged children.

PMID- 17212844
TI  - Health-enhancing physical activity among Saudi adults using the International
      Physical Activity Questionnaire (IPAQ).
AB  - OBJECTIVES: To describe the physical activity profile of Saudi adults living in
      Riyadh, using the International Physical Activity Questionnaire (IPAQ) short
      version telephone format. METHODS: Physical activity was assessed using the
      official Arabic short form of IPAQ, intended for use in telephone interview. The
      instrument asks for times spent in walking, moderate- and vigorous-intensity
      physical activity of at least 10 min duration. The sample consisted of 1616
      Saudis, between 15 and 78 years of age, living in Riyadh. Participants were drawn
      from a list of names in the telephone book using a simple random method.
      Telephone interviews were administered during the spring of 2003 by trained male
      interviewers. RESULTS: The final sample size was 1064 Saudi males and females
      (response rate of 66%), with males comprising about 66% of the respondents. Over
      43% of Saudis did not participate in any type of moderate-intensity physical
      activity lasting for at least 10 min. More than 72% of the sample did not engage
      in any type of vigorous-intensity physical activity lasting for at least 10 min.
      The proportion of Saudis who walked for 150 min or more per week was 33.3%.
      Females were engaged more in moderate physical activity than males, whereas males
      participated more in vigorous activity compared with females. Activity levels did
      not show significant relationships with education level or job hours per week.
      Based on the three activity categories established by IPAQ, 40.6% of Saudis were
      inactive, 34.3% were minimally active and 25.1% were physically active. Physical
      inactivity increased with advancing age. CONCLUSION: The data suggest that the
      prevalence of physical inactivity among Saudis adults is relatively high. Efforts
      are needed to encourage Saudis to be more physically active, with the goal of
      increasing the proportion of Saudis engaging in health-enhancing physical
      activity.

PMID- 17212845
TI  - Epidemiological survey of vitamin deficiencies in older Thai adults: implications
      for national policy planning.
AB  - OBJECTIVE: To examine the prevalence and risk factors of vitamin deficiencies
      among older Thai adults. METHODS: The cross-sectional study was conducted in four
      rural communities, one from each of the four main regions of Thailand. In total,
      2336 subjects aged 60 years and over were recruited. Anthropometric variables,
      demographic data, blood glucose and lipid profile, albumin, globulin and blood
      levels of vitamin A, beta-carotene, folic acid, vitamin B12, vitamin C, vitamin E
      and vitamin B1 were all measured. RESULTS: The prevalence of vitamin deficiencies
      was 0.6% for vitamin B12, 6.1% for vitamin A, 9.9% for vitamin C, 30.1% for
      vitamin B1, 38.8% for erythrocyte folate, 55.5% for vitamin E and 83.0% for beta
      carotene. Male gender was a common risk factor for at least three vitamin
      deficiencies, i.e. beta-carotene, folate and vitamin E. Being a manual worker was
      a common risk factor of beta-carotene and vitamin B1 deficiency. Poor income was
      found as a risk factor only in erythrocyte folate deficiency while increasing age
      was a significant factor only in vitamin C deficiency. CONCLUSION: The prevalence
      of vitamin deficiencies among older Thai people was quite different from that
      found in Western countries, reflecting different socio-economic backgrounds.
      Vitamin deficiency was not only from poor food intake but also from the dietary
      habit of monotonous food consumption in older people. Some common associated
      factors of atherosclerosis were also significantly related to folate and vitamin
      E deficiencies.

PMID- 17212846
TI  - Excluding infants under 6 months of age from surveys: impact on prevalence of pre
      school undernutrition.
AB  - OBJECTIVE: Infants aged 0-5 months are not systematically included in assessments
      of child nutritional status and are generally excluded from surveys conducted in
      emergencies. We estimated the impact of excluding 0-5-month-old infants on the
      prevalence of stunting, wasting and underweight among children under 5 years (U5)
      and under 3 years (U3) of age. DESIGN: Comparison of the prevalence of stunting,
      wasting and underweight in U5 and U3 with or without inclusion of the age group 0
      5 months. SETTING: Demographic and Health Surveys and Multiple Indicator Cluster
      Surveys from 76 developing countries and countries in transition. SUBJECTS:
      Children under 3 or under 5 years of age included in the surveys. Results
      Excluding 0-5-month-old infants resulted in an overestimation of the prevalence
      of stunting, wasting and underweight in U5 of 3.0, 0.3 and 2.6 percentage points,
      respectively, and of 4.8, 1.0 and 5.2 percentage points, respectively, in U3. The
      overestimation for wasting was negligible. The regions showing the highest
      overestimations for stunting and underweight were Asia and sub-Saharan Africa.
      Overall, countries with high prevalences of stunting and underweight showed
      especially large overestimations. The prevalence of underweight in infants aged 0
      5 months was correlated with the prevalence of low maternal body mass index.
      CONCLUSION: All surveys, even in situations of nutrition emergency, should
      include 0-5-month-old infants. Strictly comparable age ranges are essential in
      nutrition surveys for monitoring trends and evaluating programme impact. Greater
      awareness of prenatal and early child undernutrition is needed among policy
      makers.

PMID- 17212847
TI  - Adaptation and evaluation of the National Cancer Institute's Diet History
      Questionnaire and nutrient database for Canadian populations.
AB  - BACKGROUND AND OBJECTIVE: Despite assumed similarities in Canadian and US dietary
      habits, some differences in food availability and nutrient fortification exist.
      Food-frequency questionnaires designed for the USA may therefore not provide the
      most accurate estimates of dietary intake in Canadian populations. Hence, we
      undertook to evaluate and modify the National Cancer Institute's Diet History
      Questionnaire (DHQ) and nutrient database. METHODS: Of the foods queried on the
      DHQ, those most likely to differ in nutrient composition were identified. Where
      possible these foods were matched to comparable foods in the Canadian Nutrient
      File. Nutrient values were examined and modified to reflect the Canadian content
      of minerals (calcium, iron, zinc) and vitamins (A, C, D, thiamin, riboflavin,
      niacin, B6, folate and B12). DHQs completed by 13 181 Alberta Cohort Study
      participants aged 35-69 years were analysed to estimate nutrient intakes using
      the original US and modified versions of the DHQ databases. Misclassification of
      intake for meeting the Dietary Reference Intake (DRI) was determined following
      analysis with the US nutrient database. RESULTS: Twenty-five per cent of 2411
      foods deemed most likely to differ in nutrient profile were subsequently modified
      for folate, 11% for vitamin D, 10% for calcium and riboflavin, and between 7 and
      10% for the remaining nutrients of interest. Misclassification with respect to
      meeting the DRI varied but was highest for folate (7%) and vitamin A (7%) among
      men, and for vitamin D (7%) among women over 50 years of age. CONCLUSION: Errors
      in nutrient intake estimates owing to differences in food fortification between
      the USA and Canada can be reduced in Canadian populations by using nutrient
      databases that reflect Canadian fortification practices.

PMID- 17212848
TI  - Impact of nutrients on insulin-like growth factor-I, insulin-like growth factor
      binding protein-3 and their ratio in African American and white males.
AB  - OBJECTIVE: Higher levels of insulin-like growth factor-I (IGF-I) and lower levels
      of IGF binding protein-3 (IGFBP-3) have been associated with an increased risk of
      prostate cancer. Nutrition is known to partially regulate IGF levels and it is
      possible that nutritional factors mediate the impact of IGF levels on prostate
      cancer risk. DESIGN: A cross-sectional analysis of the impact of nutritional
      factors measured by a dietary questionnaire on plasma levels of IGF-I, IGFBP-3
      and their molar ratio. Multiple linear regression analysis was used to test for
      effects of nutrients on IGF levels. SETTING: Prostate cancer screening at the
      Hollings Cancer Center in Charleston, South Carolina. SUBJECTS: Ninety-five
      African American and 138 white males aged 33-83 years attending the screening.
      RESULTS: In whites, intakes of total, saturated and monounsaturated fats were
      positively associated with an increase in the molar ratio, while there was no
      association in African Americans. In African Americans, we found that increasing
      intake of calcium and dairy servings was positively associated with IGF-I levels.
      Increased vegetable intake was positively associated with IGFBP-3 in African
      Americans, while there was no effect in whites. A higher percentage of alcohol in
      the total diet was significantly associated with a decrease in the molar ratio
      and an increase in IGFBP-3 in both groups. CONCLUSIONS: Our results confirm
      previous findings of nutritional determinants of IGF levels. Additionally, we
      found the impact of several nutrients on IGF levels to be different in whites and
      African Americans, which warrants further investigation.

PMID- 17212849
TI  - Infant and child growth and health: standards, principles, practice.

PMID- 17212850
TI  - Grassroots activities, national initiatives and HIV prevention: clues to explain
      Australia's dramatic early success in controlling the HIV epidemic.
AB  - During the mid-1980s Australia experienced a remarkable decline in HIV incidence
      that can rightly be considered a public health milestone of global importance.
      The effects of this decline lasted for about 20 years and greatly benefited all
      Australians. In contrast, as we enter the mid-2000s, we see the global epidemic
      continues to intensify, HIV vaccines remain a distant possibility, and Australia
      is experiencing rising HIV incidence again. Clearly, better understanding of HIV
      prevention has important implications both for Australia and the world.
      Therefore, we believe, it is timely to revisit Australian experiences of the mid
      1980s in order to understand those early events better. To gauge the influence
      (if any) of government strategies, funding levels and other events during a
      period of dramatic decline in HIV transmission, incidence figures are mapped
      against Federal HIV/AIDS funding patterns and the occurrence of key national
      interventions and events. The analysis reveals that the greatest decline in HIV
      preceded almost all substantive initiatives undertaken at the national level,
      which are often held responsible for Australia's successful early containment of
      HIV. In particular, dramatic declines were already well advanced and/or preceded
      (i) substantive growth in national HIV/AIDS prevention education funding, (ii)
      publication of the first National AIDS Strategy, (iii) establishment of key
      national HIV/AIDS bodies and (iv) promulgation of the 'Ottawa Charter'.
      Explanations for, and lessons learned from Australia's dramatic early declines in
      HIV incidence are discussed.

PMID- 17212852
TI  - Mentoring in genitourinary medicine.
AB  - Mentoring is a process whereby one doctor (the mentor) facilitates and encourages
      another doctor (the mentee) to develop their career, in light of their own
      priorities. Mentees benefit from time dedicated to addressing their needs,
      challenging the status quo, and exploring ways to change. Mentoring schemes
      depend on the availability and enthusiasm of suitably trained mentors, as well as
      the voluntary participation of mentees. The specialty of genitourinary (GU)
      medicine is setting up such a scheme, which will initially be offered to new
      consultants. Workshops to train mentors are starting that are specifically
      tailored to our specialty. We discuss the principles and benefits of mentoring,
      different models that can be used, and potential difficulties. We also present
      the results of a survey that demonstrated widespread interest in mentoring within
      GU medicine.

PMID- 17212853
TI  - Survey of HIV and hepatitis B or C co-infection management in the UK 2004.
AB  - The objective of this study is to evaluate the current management practices of
      patients with HIV and hepatitis B or C co-infection. A postal survey was made of
      186 clinics in the UK between October 2003 and January 2004. In total, 100/186
      (54%) clinics responded: 16% estimated their hepatitis B prevalence to be above
      10%, 27% estimated their hepatitis C to be above 10%. Problems were identified in
      a minority of clinics including: not routinely screening HIV-positive patients
      for hepatitis C (6%), restrictions on diagnostic tests required for the
      management of hepatitis infection and offering inappropriate treatment for
      hepatitis B infection. The use of diagnostic liver biopsies varied and clinics
      reported restrictions on access to hepatitis C therapy, with a consequent impact
      on waiting times. In conclusion, we identified several areas of concern in the
      diagnosis and management of HIV/hepatitis co-infection in several UK HIV
      treatment centres.

PMID- 17212854
TI  - BASHH Clinical Governance Committee guidance on the appropriate use of HIV point
      of care tests.

PMID- 17212855
TI  - Presentation and reasons for HIV-1 testing in Saudi Arabia.
AB  - Clinical presentation, CD4+ T lymphocyte count at diagnosis, and reasons for HIV
      1 testing reflect the attitudes towards HIV testing and also the ability of the
      health-care system to diagnose HIV early. In a cross-sectional study from the HIV
      database in a large HIV-referral centre in Saudi Arabia, all 410 HIV-infected
      patients were included, 276 men and 134 women. Women were younger at diagnosis
      (mean age 25.5 compared with 29 years for men, P < 0.04) and had higher CD4+ T
      lymphocytes (mean 461 for women and 223 for men, P < 0.001). Out of 276 men, 90
      (33%) were identified as HIV infected when they presented with AIDS. Fifty-five
      percent of the infected women were tested for HIV-1 because of contact with an
      infected person compared with 8% of the infected men, odds ratio (OR) 13.8 (95%
      confidence interval [CI]: 7.7-24.9). AIDS remains the main presentation for HIV
      infected men. Women are diagnosed earlier and younger than men.

PMID- 17212856
TI  - Increasing resistance to ciprofloxacin and other antibiotics in Neisseria
      gonorrhoeae from East Java and Papua, Indonesia, in 2004 - implications for
      treatment.
AB  - We examined gonococci isolated in 2004, in East Java and Papua, Indonesia, to
      review the suitability of ciprofloxacin-based and other treatment regimens.
      Gonococci from the two provinces were tested in Sydney for susceptibility to
      penicillin, tetracycline, spectinomycin, ceftriaxone, ciprofloxacin, gentamicin,
      azithromycin and rifampicin. Of 163 gonococcal isolates from East Java (91) and
      Papua (72), 120 (74%) of gonococci, 62 (68%) and 58 (80%) from East Java and
      Papua, respectively, were penicillinase-producing gonococci and 162 displayed
      high-level tetracycline resistance. Eighty-seven isolates (53%) were
      ciprofloxacin resistant, 44 (48%) from East Java and 43 (60%) from Papua. All
      isolates were sensitive to cefixime/ceftriaxone, spectinomycin and azithromycin.
      Minimum inhibitory concentrations of gentamicin were in the range 0.05-8 mg/L.
      Sixty-nine gonococci (42%) showed combined resistance, to penicillin,
      tetracycline and quinolones. Quinolone resistance has now reached unacceptable
      levels, and their use for the treatment of gonorrhoea in Indonesia should be
      reconsidered.

PMID- 17212857
TI  - Immigration medical screening and HIV infection in Canada.
AB  - HIV infection, particularly associated with AIDS, is often used by migrant
      screening nations to exclude entry into the country. The unique feature of the
      Canadian immigration HIV screening programme is that it was not primarily for
      determining inadmissibility of HIV-positive applicants, but for health promotion
      and disease prevention purposes. All applicants over 15 years of age for
      permanent residency or temporary residency from designated countries are HIV
      antibody tested. This includes persons seeking asylum from within Canada. The
      highest rates of HIV infection were found in migrant applicants from high
      prevalence areas of the world and reflected the demographic profile of the source
      region (predominately women). The majorities of HIV-positive persons are exempt
      from exclusion from Canada due to class of application (refugee, family) or are
      already in Canada (refugee claimant). Significant issues in notification,
      reporting and programme management have been identified as a consequence of this
      programme.

PMID- 17212858
TI  - High HIV prevalence among patients choosing anonymous and free testing in
      Belgium, 1990-2002.
AB  - From 1990 through 2002, 25,250 anonymous and free HIV tests were performed at a
      testing site, which carried out the majority (85%) of anonymous testing in
      Belgium. During the same period, approximately 7.3 million confidential tests
      were registered nationwide. The rate of new HIV infections diagnosed at the
      anonymous testing site was 11.1/1000 tests; it was significantly higher than the
      rate observed among confidential tests (relative risk = 7.41; P < 0.0001). New
      HIV cases diagnosed through anonymous testing include a higher proportion of
      young adults (42.0% versus 32.5% in confidential testing; P < 0.001) and a higher
      proportion of men who have sex with men (32.7% vs. 25.9% in confidential testing;
      P < 0.02). Anonymous and free HIV testing was particularly sought by persons with
      higher infection risk, and efficiently contributed to HIV diagnosis in this
      population. Anonymous and free testing should be and remain an accessible
      alternative integrated in HIV testing policies.

PMID- 17212859
TI  - Factors influencing women's views on the acceptability and experience of being
      opportunistically screened for Chlamydia trachomatis in hospital settings.
AB  - A subsample of 681 women participating in a two-centred, three-setting larger
      (2817) prevalence study were approached and, with consent, administered a
      questionnaire by post or in person. The questionnaire asked about their views of
      opportunistic screening for Chlamydia trachomatis (CT). The study response rate
      was 71%. In all, 94% women reported screening should be offered and most, on a
      regular basis. About 91% thought men should be screened but only 47% thought they
      would attend. Most (89%) knew the term 'chlamydia' but fewer, (63%) knew they
      could catch CT more than once. This is one of the very few UK studies which has
      explored women's views towards the acceptability of CT screening. Results suggest
      the majority of women report that screening for the condition is acceptable but
      not all have in-depth knowledge of CT. If a screening programme is to be
      established more education regarding the condition is required.

PMID- 17212860
TI  - Lessons learned from a population-based chlamydia screening pilot.
AB  - We evaluated process organization and response optimization in a home-based
      Chlamydia trachomatis (Ct) screening project in the Netherlands among 15- to 29
      year-old women and men. The method used was computer-supported data flow, from
      population sampling to informing participants of the result. A new test kit or a
      letter reminded non-respondents after six weeks. Fifteen-year olds required
      parental consent. Urine arrived at the laboratory within 29 days from invitation,
      and four (1-11) days after collection, indicating good specimen quality. Test
      kits had a higher response than letters (15 versus 10%). Response in 15-year olds
      was 33%; with 2% Ct infected sexually active 15 year olds. In Conclusion, purpose
      made computer software is essential for an efficient screening programme. Sending
      urine by mail does not impair diagnostics. Reminders are necessary and effective
      after four weeks. Necessary parental consent for under 16-year olds should not be
      a deterrent to offer Ct screening to this age group.

PMID- 17212861
TI  - Prevalence and risk factors of squamous intraepithelial lesions of the cervix
      among HIV-infected women - a long-term follow-up study in a low-prevalence
      population.
AB  - HIV-infected women have high risk for precancerous lesions of the uterine cervix.
      We studied the prevalence and risk factors of squamous intraepithelial lesions
      (SIL) among systematically followed HIV-infected women enrolled from a population
      with low HIV prevalence. The study population consisted of 108 HIV-infected women
      enrolled between 1989 and 2003 with a mean follow-up 4.4 years. Risk factors of
      SIL were assessed based on samples collected during 2000-02. The overall rates of
      atypical glandular cells of uncertain significance (AGUS), atypical squamous
      cells of uncertain significance (ASCUS), low-grade SIL (LSIL) and high-grade SIL
      (HSIL) were 4, 24, 15 and 5%, respectively. Reduced CD4-lymphocyte count was
      associated with an increased prevalence of SIL, whereas duration of HIV infection
      (< or > or =5 years), use of antiretroviral medication, or HIV viral load (<50 or
      > or =50 copies/mL) was not. The cumulative risk of developing SIL after 1 and 5
      years was 17% (95% confidence interval [CI] 7-27%) and 48% (95% CI 33-63%),
      respectively. The cumulative risk of SIL was increased among women younger than
      31 years (P = 0.04) as well as in women displaying high initial HIV viral load (P
      = 0.01). Our results from a low HIV-incidence population re-emphasize the
      importance of guidelines for cytologic screening of HIV-seropositive women.

PMID- 17212862
TI  - Perceived risks and benefits of HIV testing, and predictors of acceptance of HIV
      counselling and testing among pregnant women in Zimbabwe.
AB  - This project evaluated perceived risks and benefits and determined predictors of
      acceptance of voluntary HIV counselling and testing (VCT) among pregnant women in
      Zimbabwe. One hundred and seventy pregnant women attending an urban antenatal
      clinic were surveyed. Implications of a negative or positive HIV test result and
      of telling a partner or community members that one is HIV positive were queried.
      Forty women (23.5%) consented to VCT, and 16 (40%) were HIV positive. Women who
      saw VCT as lower risk (odds ratio [OR] = 2.3, 95% confidence interval [CI] [1.1
      5.0]) and women who had had a stillbirth or child die (OR = 0.4, 95% CI [0.16
      0.97]) were more likely to consent. Prenatal HIV VCT offers the best opportunity
      for prevention of mother-to-child transmission of HIV; however, less than 25% of
      women consented. If such interventions are to be successful, attention must be
      directed towards developing culturally appropriate strategies to address women's
      concerns and improve future acceptance of VCT in Zimbabwe.

PMID- 17212863
TI  - Reduced fertility among HIV-infected women associated with viral load in Rakai
      district, Uganda.
AB  - We assessed whether HIV-1 viral load affects the likelihood of live birth among
      HIV-positive women in a nested case-control study of HIV-positive women from a
      community cohort in Rakai District, Uganda. Cases were women who had a live birth
      (n = 270), and controls were sexually active women who did not use contraception
      and did not become pregnant during follow-up (n = 263). In women with a live
      birth and non-pregnant controls, median HIV viral loads were 4.12 log(10)
      copies/mL and 4.41 log(10) copies/mL, respectively (P = 0.001). A non-linear
      association was observed, and a segmented linear regression with spline knot at
      4.5 log(10) copies/mL was fit. We observed a decline in the log (adjusted odds
      ratio [adj. OR])= -0.08 (95% confidence interval [CI]: -0.36, 0.20) between 3.0
      and 4.49 log(10) viral load and -0.92 (95% CI: -1.21, -0.63) between 4.5 and 6.5
      log(10) viral load. The two reductions differed significantly from one another (P
      < 0.001). Each increase in log(10) viral load after 4.5 log(10) resulted in an
      adj. OR of live birth which was 12% of the previous viral load category. Our data
      suggest that there may be considerable differences in the ability to produce a
      live birth among HIV-positive women with high viral loads.

PMID- 17212864
TI  - Comparison of outcomes of management of gonorrhoea by clinic-based test of cure
      with those by telephone follow-up.
AB  - We compared the outcomes in 278 patients managed with clinic-based test of cure
      (phase 1) for gonorrhoea with 271 patients managed with the new policy of
      telephone follow-up (phase 2). Almost 98% of the patients in both phases were
      treated within 28 days of diagnosis. Follow-up of the patients was significantly
      better with telephone follow-up (phase 2), with an increase in proportion of
      patients reviewed (76.1% compared with 59.7% in phase 1, P < 0.001). Yield of
      partner notification was 0.22 and 0.31 contacts per case of gonorrhoea within
      four weeks of treatment of the index case in phases 1 and 2, respectively.

PMID- 17212865
TI  - Audit of the management of genital herpes simplex infection.
AB  - We evaluated the management of genital herpes simplex virus (HSV) infection at
      our clinic. Over six months, 135 patients with primary HSV and 97 patients with
      recurrent HSV attended. Sixty percent of patients presenting within five days of
      primary infection were treated with oral acyclovir. Only 53% of patients with
      primary HSV were given written/verbal information. Follow-up appointments were
      attended by 78%. Seventy-seven percent of patients with recurrent HSV had at
      least one viral isolate typed and 72% of patients experiencing episodes
      exceeding, annually, six were offered suppressive therapy. Our results
      demonstrate successful management of patients with HSV infections but
      recommendations are made to reach the standards set by BASSH. Furthermore, we
      illustrate that improved documentation would go a long way in validating the
      result.

PMID- 17212866
TI  - Betadine for herpes simplex infection.
AB  - The clinical value of aciclovir, oral or topical, in the episodic treatment of
      recurrent herpes virus infection is limited. Betadine (povidone-iodine) could
      provide a cheap, effective alternative for managing symptomatic recurrences. We
      describe a case where povidone-iodine was used successfully to treat a recurrence
      of genital herpes simplex and review the literature supporting povidone-iodine in
      the treatment of genital tract infections.

PMID- 17212867
TI  - Primary care involvement in HIV management - do patients want it and can general
      practitioners deliver it?

PMID- 17212868
TI  - Survey of non-consultant career grade doctors in genitourinary medicine and
      sexual health departments 2005.

PMID- 17212869
TI  - Sustained health promotion success for migrant sex workers in Sydney.

PMID- 17212872
TI  - Lay-led self-management in chronic illness: a review of the evidence.
AB  - OBJECTIVES: In this paper, we seek to clarify what is known about self-care in
      chronic illness and the impact of lay-led self-management programmes. The main
      focus of the paper is the specific 'lay-led' interventions developed by Kate
      Lorig and her collaborators in the USA, and in the context of the English Expert
      Patients Programme (EPP). METHODS: A systematic search of relevant databases was
      undertaken. RESULTS: Seventeen articles and two conference papers met the
      criteria set. These papers documented the use of condition-specific lay-led self
      management programmes and generic lay-led self-management programmes. DISCUSSION:
      Despite the potential benefits of enhanced self-management, the review of the
      literature presented here suggests several possible problems associated with the
      presentation and implementation of initiatives such as the EPP programme. These
      include the possibility that advocates of public service improvements have on
      occasion been tempted to overstate the evidence for the relative and absolute
      effectiveness of lay-led self-management programmes. In addition, the varied
      experiences of those living with a chronic illness warn against promulgating
      rigid prescriptions about what patients -should think and do. The evidence to
      date is indicative of short-term benefits being derived from the provision of lay
      led self-management programmes.

PMID- 17212873
TI  - Damned by faint praise?

PMID- 17212874
TI  - A risk worth taking.

PMID- 17212875
TI  - Pluralistic responses to the challenge of chronic illness.

PMID- 17212876
TI  - The rural context and women's self-management of chronic health conditions.
AB  - OBJECTIVE: To examine the rural context and describe its influence on the self
      management of chronic illness by women living in a rural setting. METHODS: The
      Women to Women (WTW) project is a research-based computer intervention that
      provides health education and peer support to rural women with chronic health
      conditions. Messages posted to the online support and health education chat rooms
      were examined to determine the characteristics of the rural context in relation
      to the women's illness self-management. RESULTS: 'Distance' was the overarching
      characteristic of the rural context that influenced the women's ability to self
      manage their chronic health problems. The effect of distance was woven throughout
      each of the four predominant themes that emerged from the data as having
      influence - physical setting, social/cultural/economic environment, nature of
      women's work, and accessibility/quality of healthcare. These influences affected
      the women's self-management abilities both negatively and positively. DISCUSSION:
      The rural context profoundly influenced the ability of rural women to self-manage
      their chronic conditions. From the data, health professionals and policy-makers
      can glean information about the barriers to healthcare faced by rural women who
      are trying to manage their chronic health problems in comparative isolation.

PMID- 17212877
TI  - Social support and self-management of type 2 diabetes among immigrant Australian
      women.
AB  - OBJECTIVE: To elucidate the social meanings and interpretations that immigrant
      women attach to the diagnosis of type 2 diabetes, and the social support and
      professional advice that they receive following this diagnosis. METHODS: In-depth
      interviews were conducted with 16 immigrant women living in Melbourne, Australia,
      from communities with a higher than average incidence of type 2 diabetes. Women
      were recruited purposively through general practitioners and community
      organizations. The women's initial reaction to the diagnosis of diabetes,
      understandings of the behavioural changes required to control symptoms and
      prevent complications and the nature of the social and professional supports were
      discussed. Interviews were audio-taped, transcribed, coded and analysed
      thematically by both authors. RESULTS: Some women were critical of their doctors
      but also manipulated their encounters to avoid receiving unwelcome information
      about the progress of the disease and consequent required changes in management.
      Social interactions influenced women's adjustments to diagnosis and informed
      their communication and adaptation of their lives. Choice of support varied by
      cultural background, but many respondents reflected on the thin line between
      support and interference. All women found most understanding from others living
      with diabetes. DISCUSSION: The social context of people with type 2 diabetes is
      important in facilitating or inhibiting the management of the condition.
      Variations in attitudes to family and professionals influenced adherence to
      advice and emphasized the need for appropriate support to women to sustain
      behavioural change.

PMID- 17212878
TI  - Projection, stereotyping, and the perception of chronic medical conditions.
AB  - OBJECTIVES: To test the hypotheses that people with chronic medical conditions
      are more likely than those without chronic medical conditions to project personal
      characteristics onto the population with chronic medical conditions, and that
      people without chronic medical conditions are more likely to stereotype those
      with chronic medical conditions. METHODS: The study is a secondary analysis of
      the 2000 Chronic Illness and Caregiving survey conducted by Harris Interactive
      Inc. using linear and probit regressions. RESULTS: The hypothesis that persons
      with chronic medical conditions project their characteristics onto the population
      of those with chronic medical conditions is strongly supported. The hypothesis
      that persons without chronic medical conditions stereotype the population of
      those with chronic medical conditions is weakly supported. DISCUSSION: The
      findings imply that characterizations of persons with chronic medical conditions
      vary more among those with chronic medical conditions than among those without,
      and that those without chronic medical conditions have more homogeneous
      representations. This difference between those who have chronic medical
      conditions and those who do not implies a potential for greater variation in
      support for the particulars of policies addressing chronic medical conditions
      among those with chronic medical conditions.

PMID- 17212879
TI  - The experience of long-term diagnosis with human immunodeficiency virus: a
      stimulus to clinical eupraxia and person-centred medicine.
AB  - The biopsychosocial challenges of living with human immunodeficiency virus (HIV)
      have changed over time and they dictate the need for relevant medical services.
      The meaning of an HIV diagnosis has moved from a terminal to a manageable
      condition with the development of antiretrovirals, bringing profound changes to
      the experience of living with HIV and the meaning and use of diagnostic labels.
      Six biological stage-related categories in the literature of psychological
      medicine of HIV are critiqued. Long-term HIV highlights the inadequacy of
      physician-centred, acute-care medicine in chronic illness and its exclusion of
      preventive, psychological and rehabilitative modalities. 'Eupraxia' is presented
      as a conceptual framework for chronic care medicine, referring to best practice,
      wellbeing, best interests, and (public) welfare, through facilitated but
      collaborative approaches. A public-centred service model is proposed, using
      idiographic assessment and treatment by clinicians as patient delegates
      (proxies), monitoring joined-up care, providing group-based biopsychosocial
      treatment, facilitating autonomous and self-managing behaviour by the public,
      removing professional and practice hierarchies, and implementing real-time
      clinical and managerial accountability with public ownership and involvement.
      This model is superior in its health-and cost-effectiveness but can only work
      within a nationalized system that focuses equally on standardized outcomes and
      evidential and personalized health outcomes.

PMID- 17212880
TI  - Simulators: a new use for an old paradigm.

PMID- 17212881
TI  - Technical and technological skills assessment in laparoscopic surgery.
AB  - OBJECTIVES: Surgical appraisal and revalidation are key components of good
      surgical practice and training. Assessing technical skills in a structured manner
      is still not widely used. Laparoscopic surgery also requires the surgeon to be
      competent in technological aspects of the operation. METHODS: Checklists for
      generic, specific technical, and technological skills for laparoscopic
      cholecystectomies were constructed. Two surgeons with >12 years postgraduate
      surgical experience assessed each operation blindly and independently on DVD. The
      technological skills were assessed in the operating room. RESULTS: One hundred
      operations were analyzed. Eight trainees and 10 consultant surgeons were
      recruited. No adverse events occurred due to technical or technological skills.
      Mean interrater reliability was kappa=0.88, P=<0.05. Construct validity for both
      technical and technological skills between trainee and consultant surgeons were
      significant, Mann-Whitney P=<0.05. CONCLUSIONS: Our study demonstrates that
      technical and technological skills can be measured to assess performance of
      laparoscopic surgeons. This technical and technological assessment tool for
      laparoscopic surgery seems to have face, content, concurrent, and construct
      validities and could be modified and applied to any laparoscopic operation. The
      tool has the possibility of being used in surgical training and appraisal. We aim
      to modify and apply this tool to advanced laparoscopic operations.

PMID- 17212882
TI  - Building a laparoscopic surgical skills training laboratory: resources and
      support.
AB  - BACKGROUND: Technical skills have historically been developed and assessed in the
      operating room. Multiple pressures including resident work hour limitations,
      increasing costs of operating room time, and patient safety concerns have led to
      an increased interest in conducting these activities in a safe, reproducible
      environment. To address some of these issues, many residency programs have
      developed laparoscopic surgical skills training laboratories. We sought to
      determine the current status of laparoscopic skills laboratories across residency
      programs. METHODS: In December 2004, surveys were mailed to all 251 United States
      general surgery residency program directors. This brief 2-page survey consists of
      9 questions regarding laparoscopic skills training laboratories. RESULTS: Of the
      251 mailed surveys, 111 completed surveys were returned (44%). Of the
      respondents, 81 have laparoscopic skills training laboratories in place (80%).
      Skills laboratories that used a defined curriculum, and general surgery programs
      that shared their laboratories with other training programs were determined to
      have significantly more resources. A wide variety of funding sources have been
      used to develop and support these skills laboratories. CONCLUSIONS: Significant
      variability in training practices and equipment currently used exists between
      laboratories. A more efficient, standardized approach to skills training across
      residency programs is a desirable goal for the immediate future.

PMID- 17212883
TI  - A warm-up laparoscopic exercise improves the subsequent laparoscopic performance
      of Ob-Gyn residents: a low-cost laparoscopic trainer.
AB  - INTRODUCTION: Residents traditionally acquire surgical skills through on-the-job
      training. Minimally invasive laparoscopic techniques present additional demands
      to master complex surgical procedures in a remote 2-dimensional venue. We
      examined the effectiveness of a brief warm-up laparoscopic simulation toward
      improving operative proficiency. METHODS: Using a "Poor-Man's Laparoscopy
      Simulator," 12 Ob/Gyn residents and 12 medical students were allocated 10 minutes
      to transfer 30 tablets with a 5-mm grasper from point A to point B via
      laparoscopic visualization in a warm-up exercise. Participants repeated the
      exercise following a 5-minute pause. Mean scores, expressed in seconds/tablet,
      and overall improvement (percentage difference between warm-up and follow-up)
      were analyzed according to postgraduate standing (PGY14), dexterity skills, and
      pertinent vocational activities. RESULTS: Significant improvements were noted for
      both residents (+25%) and medical students (+29%), P<0.0001. Scores between the 2
      groups, however, were not significant (P=0.677). Proficiency was not influenced
      by PGY standing. Interestingly, the best (8.73 sec/pill) and the worst (25
      sec/pill) scores were attained by a medical student and a chief resident,
      respectively, suggesting the contribution of individual aptitude. CONCLUSION: A
      brief warm-up exercise before an actual laparoscopic surgical procedure
      significantly improves subsequent laparoscopic performance.

PMID- 17212884
TI  - Evaluation of microporous polysaccharide hemospheres for parenchymal hemostasis
      during laparoscopic partial nephrectomy in the porcine model.
AB  - OBJECTIVES: We evaluated the efficacy of Microporous Polysaccharide Hemospheres
      (MPH) for parenchymal hemostasis during laparoscopic partial nephrectomy (LPN) in
      the porcine model. METHODS: Six female farm pigs underwent a transperitoneal
      right lower-pole LPN during occlusion of the renal hilum. Renal parenchyma was
      excised using cold Endoshears. MPH was applied to the defect and the hilar clamp
      released. Animals were kept alive for one week. Before sacrifice, left LPN was
      similarly performed using MPH. Study variables included blood loss, number of MPH
      applications, hilar clamp time, hemostasis time, perioperative complications, and
      abnormalities noted at sacrifice. RESULTS: Hemostasis was achieved in all kidneys
      solely by using MPH. The average excised specimen represented 5.6% (range, 3.6 to
      8.5) of renal weight. Mean hilar clamp and hemostatic times were 12.8 minutes
      (range, 6 to 18) and 2 minutes (range, 1 to 3), respectively. Hemostasis occurred
      after one MPH application in 8 kidneys (67%). In 3 kidneys, additional MPH powder
      was required to treat minor residual bleeding. In the remaining kidney, a second
      standard MPH application was required for hemostasis. No operative complications
      were encountered. No hematomas or residual MPH was found at necropsy; however,
      small urinomas were found in 2 of 6 kidneys. CONCLUSIONS: In the experimental
      porcine model, this initial study suggests that MPH provides effective
      parenchymal hemostasis during laparoscopic resection of an exophytic kidney
      lesion.

PMID- 17212885
TI  - Transperitoneal laparoscopic pyeloplasty for pelvic kidneys with ureteropelvic
      junction obstruction in children: technique and preliminary outcomes.
AB  - BACKGROUND: Laparoscopic pyeloplasty is rapidly becoming an acceptable procedure
      for ureteropelvic junction obstruction in the pediatric population. We present
      our experience with transperitoneal laparoscopic pyeloplasty for ureteropelvic
      junction obstruction in pelvic kidneys in pediatric patients. METHODS: A
      transperitoneal laparoscopic approach was used for performing a pyeloplasty in 4
      patients, 7 months to 8 years of age (mean age, 3.14), with ureteropelvic
      junction obstruction in a pelvic kidney. RESULTS: Average operative time was 2.1
      hours (range, 1.5 to 2.8). Mean hospital stay was 2.15 days (range, 1 to 7). No
      intraoperative complications were noted. CONCLUSIONS: Transperitoneal
      laparoscopic pyeloplasty for pelvic kidneys is feasible in the pediatric
      population, and preliminary results appear to offer the same outcome as that seen
      in orthotopic kidneys.

PMID- 17212886
TI  - Laparoscopic-assisted resection of Meckel's diverticulum in children.
AB  - BACKGROUND AND OBJECTIVES: Meckel's diverticulum (MD) presents unique challenges
      for a pediatric surgeon, as it is prone to varied complications. This case series
      highlights the diverse presentations and laparoscopic management of MD in
      children. METHODS: We performed a retrospective analysis of consecutive cases of
      laparoscopic-assisted transumbilical Meckel's diverticulectomy (LATUM) performed
      by the same surgeon for incidental as well as diverse Meckel's diverticular
      complications over 20 months. RESULTS: Eight patients (5 males and 3 females)
      aged 3 years to 13 years (median, 12) underwent LATUM. Three patients had
      painless per-rectal bleeding and 1 presented with intestinal obstruction due to a
      mesodiverticular band and intestinal ischemia. Two patients had features
      masquerading as appendicitis; one had perforated MD with secondary inflammation
      of the appendix, and the other had a torsed, gangrenous MD. In 2 patients,
      incidental MD with a narrow base was noted at appendicectomy for appendicitis.
      All patients underwent successful LATUM along with appendicectomy in 4 patients.
      The operative duration was 72 minutes to 165 minutes (mean, 112.1+/-30.6). There
      were no operative complications, and no conversion to open surgery was required.
      The hospital stay was 4 days to 7 days (mean, 4.7+/-1.2). The patient with
      mesodiverticular band intestinal obstruction presented with adhesive intestinal
      obstruction 2 weeks after the surgery. Laparoscopic-assisted minilaparotomy was
      done to release the pelvic adhesions. There were no other complications during
      the follow-up (median, 11 months). CONCLUSIONS: LATUM is a simple, safe, and
      effective procedure with a better cosmetic outcome that can be performed for
      diverse manifestations of MD. The technique also allows palpation of the MD and
      avoids use of expensive staplers.

PMID- 17212887
TI  - Robotic-assisted laparoscopy in gynecological surgery.
AB  - BACKGROUND: Laparoscopic surgery has revolutionized the concept of minimally
      invasive surgery for the last 3 decades. Robotic-assisted surgery is one of the
      latest innovations in the field of minimally invasive surgery. Already, many
      procedures have been performed in urology, cardiac surgery, and general surgery.
      In this article, we attempt to report our preliminary experience with robotic
      assisted laparoscopy in a variety of gynecological surgeries. We sought to
      evaluate the role of robotic-assisted laparoscopy in gynecological surgeries.
      METHODS: The study was a case series of 15 patients who underwent various
      gynecologic surgeries for combined laparoscopic and robotic-assisted laparoscopic
      surgery. The da Vinci robot was used in each case at a tertiary referral center
      for laparoscopic gynecologic surgery. An umbilicus, suprapubic, and 2 lateral
      ports were inserted. These surgeries were performed both using laparoscopic and
      robotic-assisted laparoscopic techniques. The assembly and disassembly time to
      switch from laparoscopy to robotic-assisted surgery was measured. Subjective
      advantages and disadvantages of using robotic-assisted laparoscopy in
      gynecological surgeries were evaluated. RESULTS: Fifteen patients underwent a
      variety of gynecologic surgeries, such as myomectomies, treatment of
      endometriosis, total and supracervical hysterectomy, ovarian cystectomy, sacral
      colpopexy, and Moskowitz procedure. The assembly time to switch from laparoscopy
      to robotic-assisted surgery was 18.9 minutes (range, 14 to 27), and the
      disassembly time was 2.1 minutes (range, 1 to 3). Robotic-assisted laparoscopy
      acts as a bridge between laparoscopy and laparotomy but has the disadvantage of
      being costly and bulky. CONCLUSION: Robotic-assisted laparoscopic surgeries have
      advantages in providing a 3-dimensional visualization of the operative field,
      decreasing fatigue and tension tremor of the surgeon, and added wrist motion for
      improved dexterity and greater surgical precision. The disadvantages include
      enormous cost and added operating time for assembly and disassembly and the
      bulkiness of the equipment.

PMID- 17212888
TI  - Laparoscopic appendectomy in pregnancy: a case series of seven patients.
AB  - BACKGROUND: Appendicitis in the pregnant patient presents with diagnostic
      difficulties and more serious problems. Open surgery has its own limitations,
      mostly governed by the stage of the disease and the trimester of pregnancy.
      Laparoscopic appendectomy is beginning to be recognized as standard appendicitis
      treatment, as evidenced by several studies. In pregnancy, laparoscopy is even
      more controversial. Several studies prove the safety of laparoscopy and some
      studies disprove it. METHODS: We have treated 7 patients in the last 10 years; 6
      had acute appendicitis and 1 had a perforated appendix. Ultrasound diagnosed 5
      patients, and CT scan identified the other 2 patients. The patient with the
      perforated appendix had free fluid in the right iliac fossa and pelvis.
      Laparoscopic appendectomy was done in all patients. DISCUSSION: Pregnancy poses
      its own unique problems to the surgeon and anesthesiologist. The normal
      physiology becomes altered, and sound knowledge of this is necessary to handle
      these patients. Clinical presentation was mostly straightforward. Both ultrasound
      and CT scan were useful investigations. CONCLUSION: Most studies support the use
      of laparoscopy in the management of appendicitis. There was no mortality (for
      mother and fetus) or morbidity in our patients.

PMID- 17212889
TI  - Gastrogastric fistula: a possible complication of Roux-en-Y gastric bypass.
AB  - BACKGROUND: Gastrogastric fistula is a communication between the proximal gastric
      pouch and the distal gastric remnant, rarely described in the realm of bariatric
      procedures. The aim of this study was to review the existing literature about
      this topic and to demonstrate its laparoscopic treatment. METHODS: An extensive
      literature review found several articles reporting this complication. However, no
      citation was found describing the steps of the laparoscopic management of this
      situation. RESULTS: Gastrogastric fistula occurs in up to 6% of Roux-en-Y gastric
      bypasses. Two theories exist for fistula formation: (1) it is a technical
      complication derived from the incomplete division of the stomach during the
      creation of the pouch, and (2) it occurs after a staple-line failure, developing
      a leak with an abscess, which then drains into the distal stomach forming the
      fistula. Early symptoms include fever, tachycardia, and abdominal pain. Failure
      in weight loss is a late clinical sign observed in these patients. Diagnosis is
      based on radiologic study, upper endoscopy and computed tomography. When
      identified in the acute postoperative course, laparoscopic treatment is easy.
      Chronic fistulas are difficult to manage, and the laparoscopic approach is an
      alternative to open surgery. CONCLUSIONS: Gastrogastric fistula is a possible
      complication of Roux-en-Y gastric bypass and its laparoscopic treatment is
      feasible.

PMID- 17212890
TI  - Gallstones: best served hot.
AB  - BACKGROUND: Acute episodes of gallstone-related diseases have traditionally been
      managed conservatively. In the event of gallstones obstructing the common bile
      duct, patients had endoscopic extraction of calculi with interval cholecystectomy
      after 4 weeks to 6 weeks when acute inflammatory changes have subsided. This
      placed the patient at risk of recurrent cholecystitis, pancreatitis, or other
      complications of cholelithiasis. METHODS: Patients presenting with acute
      gallstone-related diseases were investigated and underwent laparoscopic
      cholecystectomy during the same admission according to a predetermined treatment
      protocol. RESULTS: All patients (119) treated according to the study protocol had
      good results, with no 30-day mortality and no biliary tract injuries. One patient
      had bleeding from the cystic artery, and 6 patients required conversion to open
      cholecystectomy. CONCLUSION: Growing expertise in laparoscopic cholecystectomy
      has made it possible for surgeons to perform safe cholecystectomy in the presence
      of acute gallstone-related disease. Our experience of managing gallstone disease
      with prompt cholecystectomy during the index admission shows that this approach
      provides better, safer, and more cost-effective patient care.

PMID- 17212891
TI  - Inadvertent enterotomy in minimally invasive abdominal surgery.
AB  - BACKGROUND: Inadvertent enterotomy (IE) in laparoscopic abdominal surgery is
      underreported. Patients with a prior history of laparotomy are at significantly
      increased risk of enterotomy if another operation is needed. The incidence of
      enterotomy in laparoscopic surgery may even be greater than that during an open
      procedure and may go unrecognized due to the limited field of vision. The purpose
      of this study was to report the incidence of inadvertent enterotomy in a variety
      of laparoscopic abdominal procedures at our institution and discuss ways to
      minimize the risk of this complication. METHODS: Using the data from morbidity
      and mortality conferences, we retrospectively reviewed all complications from
      3,613 consecutive patients who had laparoscopic abdominal surgery from November
      1998 through November 2004. Patients with inadvertent enterotomy were divided
      into 4 groups according to the type of laparoscopic procedure. Inadvertent
      enterotomy was defined as any transmural penetration of any part of the
      intestine. All inadvertent enterotomies that occurred during laparoscopic
      abdominal surgery were analyzed for mechanism of injury and method of repair,
      whether diagnosis was made intraoperatively or postoperatively, clinical
      presentation, conversion rate, and whether a second procedure was necessary.
      RESULTS: Laparoscopic operations were performed in 3,613 persons. Patients
      diagnosed with IE were divided into 4 groups: Group #1: cholecystectomy; Group
      #2: all patients requiring intestinal resection with or without primary
      anastomosis; Group #3: patients with any type of hernia repair; Group #4: all
      patients that had adhesiolysis as a primary indication for the operation. The
      incidence of IE according to each group was 0.39% (8/2,016), 0.8% (3/375), 1.9%
      (6/312), 100% (4/4), respectively. Twenty patients had 21 inadvertent
      enterotomies (4 men, 16 women; mean age, 60.9 years). One patient had 2
      operations and had an enterotomy both times. Four patients (4/21, 19%) with
      unrecognized IE were diagnosed postoperatively. The overall incidence of IE was
      0.58%. No deaths occurred. CONCLUSION: Inadvertent enterotomy in laparoscopic
      abdominal surgery is especially dangerous if unrecognized during the primary
      operation. The incidence of IE can be significantly reduced with careful
      individualized risk assessment. Only surgeons who are trained in advanced
      laparoscopy should attempt complicated cases and must always be wary of possible
      bowel injury. Any patient with signs of peritonitis, sepsis, or increased
      abdominal pain after laparoscopic surgery must promptly be investigated. The
      department culture of intraoperative cooperation helped improve outcomes.

PMID- 17212892
TI  - Total extraperitoneal preperitoneal laparoscopic hernia repair using spinal
      anesthesia.
AB  - BACKGROUND: Laparoscopic herniorrhaphy is a well-debated approach to inguinal
      hernia repair. Multiple technical and outcome variables have been compared with
      those of traditional open inguinal hernia repairs. One of these variables is the
      choice of anesthesia. To date, no reports describe the use of spinal anesthesia
      for laparoscopic hernia repairs. We present herein a review of our experience
      with spinal anesthesia for the total extraperitoneal preperitoneal laparoscopic
      hernia repair (TEP). METHODS: We prospectively reviewed 30 patients undergoing
      TEP while under spinal anesthesia. Methods of anesthesia, surgical procedure,
      operative and anesthesia delivery times, as well as outcomes were reviewed.
      Patients were followed up over a 2-year period. Short- and long-term results of
      the surgical procedure and anesthesia delivered were noted. RESULTS: All patients
      underwent successful laparoscopic hernia repair while under spinal anesthesia
      without conversion to general anesthesia. Forty-four hernias were repaired in 30
      patients. Short- and long-term follow-up (2 years) revealed no significant
      untoward affects from the spinal anesthesia in this series of patients. Aside
      from inguinodynia in 3 patients in the short-term, no other short-term or long
      term untoward sequelae occurred. CONCLUSIONS: Spinal anesthesia is a feasible,
      and in our experience, the preferable method of anesthesia for total
      extraperitoneal laparoscopic hernia repair.

PMID- 17212893
TI  - Infiltration of suture sites with local anesthesia for management of pain
      following laparoscopic ventral hernia repairs: a prospective randomized trial.
AB  - BACKGROUND: Postoperative pain control after laparoscopic ventral hernia repairs
      remains a significant clinical problem. We sought to determine the pain-sparing
      efficacy of local anesthetic infiltrated into the abdominal wall wounds created
      by the placement of transabdominal sutures used to ensure adequate fixation of
      the mesh during laparoscopic ventral hernia repair. METHODS: Patients undergoing
      laparoscopic ventral/incisional hernia repair were randomized to receive local
      anesthesia (0.25% bupivacaine with epinephrine) into all layers of the abdominal
      wall to the level of the parietal peritoneum at suture fixation sites immediately
      before suture placement (Group I; n=9) or no local anesthesia (Group II, control;
      n=9). The anesthetic technique was otherwise standard for both groups.
      Postoperatively, pain was assessed with a 10-point visual analogue scale (VAS) at
      1, 2, 4, and 24 hours. Analgesic use and hospital stay were also recorded.
      RESULTS: The groups were similar in age, sex, ASA, and size of hernia defect. The
      operative times were not statistically different between the 2 groups (Group I,
      118+/-12 minutes; Group II, 144+/-21 minutes; P>0.05). Group I had a
      statistically significant decrease in the pain scores compared with Group II
      (2.2+/-0.8 vs. 6.4+/-0.9; P<0.05) at 1 hour postoperatively. At 2 and 4 hours,
      the mean pain scores were decreased but not statistically different. Similarly,
      the cumulative consumption of pain medication at 1, 2, and 4 hours
      postoperatively as well as the average hospital stay (Group I, 2.0+/-0.4; Group
      II, 2.4+/-0.4 days) were lower but not statistically significant in patients in
      Group I compared with those in Group II. CONCLUSION: This small, randomized study
      demonstrates that infiltration of suture fixation sites is effective in reducing
      early postoperative pain but not analgesic consumption following laparoscopic
      incisional and ventral hernia repairs. A larger study is required to investigate
      this strategy on later postoperative pain and hospital stay.

PMID- 17212894
TI  - Laparoscopic management of acute torsion of the omentum in adults.
AB  - BACKGROUND: Acute torsion of the greater omentum is a rare cause of acute abdomen
      in adults. We report our experience on the clinical presentation, diagnosis,
      treatment, and outcome of this condition. METHOD: This is a retrospective review
      of 9 patients who had a clinicopathologic diagnosis of acute torsion of the
      greater omentum and were treated at the Department of Surgery, Pamela Youde
      Nethersole Eastern Hospital from January 1994 to March 2004. Eight patients were
      male and 1 was female with a median age of 43 years (range, 24 to 65). Median
      body mass index was 24 kg/m(2) (range, 22 to 24). All presented with acute
      abdominal pain with a median temperature of 36.8 degrees C (range, 36.5 to 37.2)
      and a median white cell count of 9.5 x 10(9)/L (range, 7.4 to 15.1 x 10(9)).
      Preoperative ultrasound was done in 5 patients. RESULTS: All diagnoses were made
      during surgery. Resection of the infarcted omentum was performed for all patients
      (5 laparoscopic resections and 4 open resections). No postoperative complications
      occurred. The overall median time from admission to operation was 23 hours
      (range, 2 to 98). The overall median operating time and postoperative stay were
      70 minutes (range, 38 to 105) and 3 days (range, 1 to 6), respectively. The
      median oral and parenteral analgesic requirement for postoperative pain control
      was less and the median hospital stay was shorter in patients who underwent
      laparoscopic resection. CONCLUSION: Acute torsion of the greater omentum is an
      uncommon cause of acute abdomen in adults, and preoperative diagnosis is usually
      difficult. Laparoscopy seems a safe and minimally invasive technique for both
      diagnosis and treatment of this rare disease entity.

PMID- 17212895
TI  - Factors leading to long-term hospitalization after laparoscopic appendectomy.
AB  - BACKGROUND: Randomized studies demonstrate that laparoscopic appendectomy yields
      better results compared with open techniques. We sought to identify factors that
      determine an extended hospital stay among patients undergoing laparoscopic
      appendectomy. METHODS: This was a prospective study including 669 patients
      undergoing laparoscopic appendectomy. We analyzed variables that can predict the
      length of hospital stay. RESULTS: Of 669 patients undergoing laparoscopic
      appendectomy, 141 stayed in the hospital for > or = 5 days (Group 1), and 97
      stayed in the hospital for < or = 1 day after surgery (Group 2). The univariate
      analysis demonstrated that fever (P<0.0001), nausea and vomiting (P=0.060),
      leukocytosis (P<0.0001), gangrened or perforated intraoperative appearance of the
      appendix (P<0.0001), and appendix position behind the ileocecal junction
      (P<0.001) were related to a longer hospital stay. The multivariate analysis
      through logistical regression showed that the factors independently and
      significantly associated with an extended hospital stay were presurgical fever,
      appendix position behind the ileocecal junction, and intraoperative gangrened or
      perforated appearance of the appendix. CONCLUSION: Fever, appearance, and
      position of the appendix are factors related to an extended hospital stay.

PMID- 17212896
TI  - Sex as a factor in conversion from laparoscopic cholecystectomy to open surgery.
AB  - OBJECTIVES: Although laparoscopic cholecystectomy has become the standard
      treatment for symptomatic gallbladder diseases, conversion to open surgery is
      required in a substantial proportion of patients. In this study, we attempted to
      clarify whether male sex carries an increased risk for conversion to open surgery
      during laparoscopic cholecystectomy. METHODS: This study comprised 80 patients
      (41 females, 39 males) with symptomatic gallbladder stones. Average age was 39.2
      years, and all female patients were of reproductive age. Patients were excluded
      from the study if they had acute cholecystitis, previous abdominal surgery,
      systemic or connective tissue diseases, or were using tobacco, alcohol, or
      medications that affect wound healing or inflammation. Tissue samples were
      obtained from the same sites in each gallbladder wall and pericholecystic tissue
      for the measurement of tissue hydroxyproline (HP) and collagen. Samples were
      examined under light microscopy for histopathology. Findings in male and female
      patients were compared by using the Student t test. RESULTS: All patients except
      3 males received laparoscopic cholecystectomy. Conversion to open cholecystectomy
      was necessary in those 3 because of intense pericholecystic fibrosis. In male
      patient samples, macrophages were twice as numerous as in female samples, whereas
      mast cells in the men were 4 times more numerous, and eosinophils were 6 times
      more numerous (P<0.01). In men, HP levels in the gallbladder wall and
      pericholecystic tissue were 23.4+/-14.9 microg/mg dry tissue and 25.2+/-13.1
      microg/mg dry tissue, respectively. The corresponding values in women were 13.1+/
      9.4 microg/mg dry tissue and 14.5+/-8.1 microg/mg dry tissue. This higher level
      of tissue HP in men was statistically significant (P<0.015). Tissue collagen
      levels both in the submucosal area of the gallbladder wall and in pericholecystic
      tissue were significantly higher in men than in women (P<0.05). CONCLUSION: Our
      data suggest that in the context of symptomatic gallbladder stones, inflammation
      and fibrosis are more extensive in men than in women. These findings may help
      explain why the rate of conversion to open surgery is higher in men than in
      women.

PMID- 17212897
TI  - Intraluminal approach for resection of a gastric ulcer: a case report.
AB  - Laparoscopy, both diagnostic and therapeutic, has been used in the management of
      gastric pathology because of all the benefits of a minimally invasive procedure,
      such as faster recovery, shorter hospital stay, fewer wound complications, and
      other benefits. We report a case involving the resection of a gastric ulcer in a
      71-year-old patient. Endoscopy revealed a nonhealing antral ulcer that was not
      acutely bleeding. With a combined endoscopic and laparoscopic approach, we
      successfully performed a wide resection by using 2-mm instruments. Laparoscopy
      was needed to orient the lesion so that a transgastric intraluminal resection
      could be performed with 2-mm instruments. This case illustrates the feasibility
      of using a combined endoscopic and laparoscopic technique to treat a lesion that
      would otherwise require a formal resection.

PMID- 17212899
TI  - Intrathoracic gallstones: a case report and literature review.
AB  - BACKGROUND: Laparoscopic cholecystectomy is one of the most commonly performed
      procedures in general surgery. There have been very few reported thoracic
      complications from this surgical procedure. METHODS: We report the case of a
      patient who underwent a laparoscopic cholecystectomy with gallstone spillage 34
      months before presenting to the thoracic surgery service. The patient first
      complained of streaks of hemoptysis at 6 months from the time of the original
      procedure. A lower lobe infiltrate was noted and treated successfully with oral
      antibiotics. Over the next 2 years, the patient's symptoms waxed and waned.
      RESULTS: Due to the chronic infiltrate in his lung, a thoracotomy was performed
      that revealed erosion of the stone through the right diaphragm with formation of
      a lung abscess. CONCLUSION: A high index of suspicion for a gallstone-related
      problem should be entertained by the practitioner when presented with a patient
      who has a right lung infiltrate and a history of open or laparoscopic
      cholecystectomy.

PMID- 17212898
TI  - Laparoscopic wedge resection of gastric leiomyoma.
AB  - Gastric leiomyoma is a rare gastric neoplasia. The laparoscopic method may treat
      various gastric tumors, including benign leiomyoma by wedge resection without
      opening the gastric cavity. The laparoscopic approach to submucosal tumors of the
      stomach is technically feasible, is safe, and has good postoperative results. It
      should be considered a viable alternative to open surgery. Herein, we describe a
      case of laparoscopic wedge resection of gastric leiomyoma.

PMID- 17212900
TI  - Bile causing an acute scrotum immediately after laparoscopic cholecystectomy.
AB  - We report our experience with a patient that developed an acute right hemiscrotum
      immediately after undergoing an uncomplicated laparoscopic cholecystectomy for
      gallbladder dyskinesia. The etiology of the acute scrotal pain was due to bile
      which was spilled into the peritoneum after entry into the gallbladder during
      dissection. The bile obtained access to the right hemiscrotum via a communicating
      hydrocele. To the best of our knowledge this is the first report of bile causing
      an acute scrotum following laparoscopic surgery. A review of the current
      literature on the topic of the postoperative acute scrotum follows our case
      presentation.

PMID- 17212901
TI  - Simultaneous bilateral laparoscopic adrenalectomy is safe for synchronous large
      adrenal tumors.
AB  - Laparoscopy is now considered the gold standard for treating benign monolateral
      adrenal lesions. We present the case of a patient affected by Cushing's syndrome
      due to large bilateral adrenal adenomas (7.5 cm) who underwent simultaneous
      laparoscopic bilateral adrenalectomy. An anterior, lateral transperitoneal
      approach was used. Operative time was 200 minutes, and blood loss was 200 mL. No
      intraoperative complications were encountered. The postoperative course was
      uneventful, and the patient was discharged after 3 days. Laparoscopic bilateral
      adrenalectomy is a safe, effective procedure when performed by experienced hands
      and may be an alternative treatment for large adrenal lesions.

PMID- 17212902
TI  - Laparoscopic cholecystectomy in a patient with situs inversus totalis:
      feasibility and technical difficulties.
AB  - Situs inversus is a rare anomaly characterized by transposition of organs to the
      opposite side of the body. In patients with this anomaly, cholelithiasis is
      observed with a frequency similar to that in the normal population. Herein, we
      report on a patient with situs inversus totalis who underwent laparoscopic
      cholecystectomy for mucocele of the gallbladder. Diagnostic pitfalls and
      technical difficulties of the operation with technical options are discussed in
      the context of the available literature. Difficulty is encountered particularly
      in skeletonizing the structures in Calot's triangle, which consumes extra time
      and is more demanding than in patients with a normally located gallbladder. A
      summary of an additional 32 similar cases reported in the medical literature is
      also presented.

PMID- 17212903
TI  - Urachal adenocarcinoma: incidental finding at the time of surgery for ruptured
      appendicitis.
AB  - BACKGROUND: The urachus is a vestigial structure between the dome of the bladder
      and the umbilicus. Tumors may develop from the remnants, most of which are well
      differentiated, mucinous adenocarcinomas. Urachal adenocarcinoma is an
      exceedingly rare type of tumor. METHODS: We present a case of a 51-year-old
      female presenting to our institution with complaints of abdominal pain for 36
      hours. The patient was taken to the operating room for an acute appendicitis.
      Laparoscopy was performed, and gross purulence and appendiceal perforation were
      noted as well as a mass on the anterior abdominal wall. Based on the location of
      the mass, we converted to an open midline laparotomy to treat both the perforated
      appendicitis and to remove the mass. RESULTS: Pathology confirmed the diagnosis
      of perforated appendicitis and a mucinous-producing urachal adenocarcinoma.
      DISCUSSION: Data support both open and laparoscopic approaches for appendicitis.
      This case, although rare, highlights the importance of laparoscopy in a complete
      and thorough examination of the abdominal cavity. A standard right lower quadrant
      incision for an open technique would likely have resulted in omission of this
      lesion, and the patient would have presented at a more typical late stage of her
      cancer development with significantly more morbidity.

PMID- 17212904
TI  - Laparoscopic management of rudimentary uterine horn pregnancy: case report and
      literature review.
AB  - BACKGROUND: Pregnancy in the rudimentary uterine horn is an extremely rare
      clinical condition. Treatment includes surgical removal of the rudimentary horn.
      METHODS: A rudimentary horn pregnancy was reported that occurred after
      intrauterine insemination. Similar cases treated with laparoscopic surgery
      reported in the peer-reviewed journals were reviewed as well. RESULTS: Pregnancy
      in the right rudimentary horn of 6-weeks gestational age was successfully treated
      with laparoscopic surgery. CONCLUSION: Laparoscopy is a feasible and safe method
      for treating rudimentary horn pregnancy.

PMID- 17212905
TI  - Be prepared: what's in your game bag?

PMID- 17212906
TI  - Sudden unexplained death in epilepsy during physical activity.

PMID- 17212907
TI  - Screening for catastrophic neck injuries in sports.
AB  - The cervical spine is prone to injury due to the structure of the articulating
      vertebrae at the level of C4-C6, where the spinal cord occupies more of the
      spinal canal. Cervical spine injuries can occur in all sports and all ages.
      Participation in contact sports certainly increases the possibility of cervical
      spine injuries. In screening for catastrophic neck injuries it is vital to
      examine incidence and injury surveillance statistics in sports. These data can
      help determine sport-specific preponderance of catastrophic injury. Screening
      methods for predisposition to catastrophic cervical spine injuries include a
      concise history, physical examination, and radiographic methods. There is
      currently no universal classification system utilizing imaging of the cervical
      spine that has been validated as a screening method for catastrophic neck
      injuries.

PMID- 17212908
TI  - Medical-legal issues of mild traumatic brain injury.
AB  - Numerous concussions/mild traumatic brain injuries occur each year during
      athletic participation by a variety of athletes not only in the United States but
      around the globe. A variety of standards-type statements have been developed by
      various athletic and sports medicine groups that can be used to improve and
      standardize the diagnosis and treatment of these injuries. These standards can
      also be used to assist practitioners in sports medicine clearance for
      participation and return-to-play decisions. In a medical-legal arena these
      statements can be used to support the care that is provided to athletes and thus
      serve as a "shield" to medical-legal claims and suits. However, these standards
      can also be used to attack the service that is provided and then be used as a
      "sword." Legal issues surrounding standards statements regarding these injuries
      and the diagnosis and management of them should be recognized and appreciated by
      sports medicine providers and used to balance the applicable medical and legal
      risks associated with their practices.

PMID- 17212909
TI  - The dizzy athlete.
AB  - Dizziness is a common complaint both in athletes and their nonathletic
      counterparts. The diagnosis and treatment of dizziness is not significantly
      different between the two groups. The first step in evaluation involves defining
      dizziness as either presyncope, vertigo, disequilibrium, or nonspecific
      dizziness. Once the symptoms are better defined, the evaluation should then
      proceed with a careful history, physical examination, and appropriate diagnostic
      tests as indicated. Treatment strategies can be targeted at the underlying cause
      with the goal of diminishing or resolving the symptoms as well as preventing
      their recurrence. This article focuses on the diagnosis of dizziness and
      subsequent treatment regimens with particular attention paid to presyncope and
      vertigo.

PMID- 17212910
TI  - On-field issues of the C-spine-injured helmeted athlete.
AB  - Football is a violent collision sport and can lead to various serious injuries.
      Cervical spine injuries are numerous, ranging from bony fractures and
      dislocations to spinal cord disruption. These injuries can be a devastating and
      debilitating. Although most injuries that occur are self-limiting there is a
      significant proportion that can cause permanent disability. Due to the equipment
      used in football, unique on-field care is implemented in evaluating athletes with
      possible cervical spine injury. Early preseason preparation and proper on-field
      intervention can help improve outcomes for these athletes.

PMID- 17212911
TI  - Sacral stress fracture in a marathon runner.
AB  - Athletically caused sacral stress fractures represent an uncommon reason for low
      back pain. The clinician must consider this possible diagnosis when evaluating
      patients with nonradicular low back or buttock pain. Women distance runners are
      more commonly afflicted. Athletically caused sacral stress fractures are most
      often unilateral. This case report presents an illustrative case of bilateral
      sacral stress fracture occurring in a male runner.

PMID- 17212912
TI  - Unilateral cervical nerve injuries: brachial plexopathies.
AB  - Brachial plexus injuries are frequently encountered in sports. Classically, the
      symptoms include transient burning, pain, and occasionally weakness of an
      isolated upper extremity resulting from a peripheral nerve injury of varying
      degrees. Persistent symptoms or recurrent injuries may necessitate imaging such
      as electromyography. Medical personnel should be familiar with brachial plexus
      anatomy and the common nerve injury mechanisms of compression or traction. On
      field assessment includes evaluation for potentially more serious neurologic
      injuries and possible return to play when symptoms have resolved and the athlete
      has good range of motion and strength. Evidence-based guidelines are largely
      lacking, resulting in challenging evaluation and return-to-play decisions.
      Management focuses on improving neck range of motion and strength in addition to
      assessing for proper sport-specific technique. Additionally, enhancing protective
      equipment may prevent brachial plexus injuries. Currently, global screening via
      imaging of athletes is not recommended.

PMID- 17212913
TI  - Lumbar spinal stenosis.
AB  - Lumbar spinal stenosis (LSS) is a narrowing of the spinal canal with cord or
      nerve root impingement resulting in radiculopathy or pseudoclaudication. It is a
      common diagnosis that is occurring with increased frequency in sports medicine
      clinics. Symptoms include radicular pain, numbness, tingling, and weakness.
      Peripheral vascular disease presents similarly and must be considered in the
      differential diagnosis. Imaging for LSS usually begins with plain radiographs,
      but often requires additional testing with MRI or CT myelography. There are
      currently limited controlled data regarding both conservative and surgical
      treatment of LSS. Most physicians agree that mild disease should be treated
      conservatively with medications, physical therapy, and epidural steroid
      injections. Severe disease appears to be best treated surgically; laminectomy
      continues to be the gold standard treatment.

PMID- 17212914
TI  - Return-to-play decisions after cervical spine injuries.
AB  - This article summarizes the current evidence and expert opinion on making return
      to-play decisions after cervical spine injuries. Injuries discussed include
      fractures, central cord neuropraxia, stringers, disc herniations, strains,
      sprains, and instability. Each of these injuries may be complicated by
      coexistence of other conditions making return-to-play decisions more complicated.
      The congenital, developmental, and disease processes discussed include spear
      tackler's spine, congenital and developmental stenosis, Klippel-Feil syndrome,
      odontoid abnormalities, rheumatoid arthritis, spina bifida, and Arnold-Chiari
      malformations. Postsurgical considerations are also discussed. This review
      represents an abundant amount of expert opinion that was overwhelmingly based on
      case series, case reports, and biomechanical studies to support the return-to
      play guidelines.

PMID- 17212915
TI  - Current concepts in the diagnosis and treatment of spondylolysis in young
      athletes.
AB  - Spondylolysis is common among young athletes and should be suspected in any young
      athlete presenting with low back pain that persists for more than a few weeks.
      Diagnostic evaluation typically includes plain radiographs followed by more
      sensitive modalities, including single-photon emission CT, CT, or MRI. There is
      no consensus on the most appropriate protocol for diagnostic evaluation.
      Treatment usually consists of rest and/or bracing to allow healing to occur,
      followed by rehabilitation that includes core strengthening. More large-scale
      controlled studies need to be done in order to clarify the most effective
      diagnostic and therapeutic protocols.

PMID- 17212917
TI  - [Are obesity, eating habits and sadentarism inseparable?].

PMID- 17212918
TI  - [CDX2: a transcription factor with multiple tasks for epithelial cells of the
      digestive tract].

PMID- 17212919
TI  - [Oxidative stress, smoking and CFTR: can cystic fibrosis be acquired?].

PMID- 17212920
TI  - [NTS2 receptor: slamming the brakes on pain].

PMID- 17212921
TI  - [Regulation of gene expression by calmodulin in plants].

PMID- 17212922
TI  - [Calcium and olfaction in an insect model: activity marker and actor of
      plasticity].

PMID- 17212923
TI  - [Calcium and the control of C(4) photosynthesis].

PMID- 17212924
TI  - [Notch ligands Delta and lymphoid development niches].

PMID- 17212925
TI  - [Inhibition of the PD-1 pathway restores the effector function of HIV-specific T
      cells].

PMID- 17212926
TI  - [Notch signalling pathway and early mammalian embryogenesis].

PMID- 17212927
TI  - [Chromatin dynamics during the repair of DNA lesions].

PMID- 17212928
TI  - [A novel function for renal collecting duct intercalated cells: defense against
      uropathogenic Escherichia coli].

PMID- 17212929
TI  - [Impact of beta-catenin signaling pathway on stem cell differentiation in the
      skin].

PMID- 17212930
TI  - [Identification of human opiorphin, a natural antinociceptive modulator of opioid
      dependent pathways].

PMID- 17212932
TI  - [Role of P/Q calcium channel in familial hemiplegic migraine].
AB  - Voltage-dependent calcium channels constitute one of the main pathways of calcium
      entry into neurons. They are the principal actors of synaptic transmission by
      controlling the release of neurotransmitters. They also contribute to numerous
      other cell functions, such as gene expression or synaptogenesis. These channels,
      by their essential cell functions, are at the origin of numerous channelopathies
      resulting from mutations of the genes encoding their different subunits. Familial
      Hemiplegic Migraine (FHM) represents one such example of these channelopathies.
      In this human disease, genetic studies have demonstrated the implication of the
      CACNA1A gene in a type 1 form of FHM. This gene encodes for the Ca(v)2.1 subunit
      of P/Q calcium channels and is the target of numerous mutations affecting the
      properties of channel activity. The question on how discrete mutations of this
      gene are able to alter the activity of the channel and contribute to the
      physiopathology of FHM remains an open question. The functional characterization
      of mutated channels in various heterologous expression systems, as well as in
      vivo in an animal model, provides a molecular scheme of the physiopathology of
      FHM in which neurons, astrocytes and blood circulation act in concert.

PMID- 17212933
TI  - [Role of Ca(2+) in the pacemaker-like property of spinal motoneurons].
AB  - It is generally accepted that locomotion in vertebrate species is produced by
      signals coded and integrated by neurons of the spinal cord. In fact, the basic
      features of locomotion, including patterns and rhythms, are generated by a
      network of neurons called the CPG (central pattern generator) essentially
      localized in the lumbar segments of the spinal cord. However, the detailed
      mechanisms underlying the rhythmic aspect of CPG-generated locomotion are not
      fully understood. Here, we report data of studies that focus on the role of
      Ca(2+)-related mechanisms involved in the expression of the pacemaker property of
      lumbar motoneurons that innervate the hindlimbs. In fact, it has become
      increasingly clear that Ca(2+) plays a determinant function in the expression of
      this active and conditional rhythmic property. In addition to NMDA-mediated
      currents (NMDA is an agonist of the calcium permeable ionotropic glutamatergic
      receptor) and to a Ca(2+)-dependent K(+) current that were found twenty years ago
      to contribute to intrinsic voltage oscillations in motoneurons, a pivotal role
      for voltage-gated channels (e.g., CaV1.3) and intracellular Ca(2+) concentrations
      ([Ca(2+)]i) have recently been shown. Increasing evidence of a role for
      metabotropic receptor subtypes, calmodulin (a calcium binding protein), ryanodine
      and IP3-sensitive intracellular stores of Ca(2+) suggests that additional
      mechanisms are yet to be identified. A detailed understanding of the complex role
      of Ca(2+) in mediating the auto-rhythmic property of spinal neurons may
      contribute to the development of novel therapeutic approaches to induce
      locomotion after spinal cord injury.

PMID- 17212934
TI  - [Innate immunity: structure and function of TLRs].
AB  - The innate immune system provides the first line of defence against infection.
      Through a limited number of germline-encoded receptors called pattern recognition
      receptors (PRRs), innate cells recognize and are activated by highly conserved
      structures expressed by large group of microorganisms called pathogen-associated
      molecular patterns (PAMPs). PRRs are involved either in recognition (scavenger
      receptors, C-type lectins) or in cell activation (Toll-like receptors or TLR,
      helicases and NOD molecules). TLRs play a pivotal role in cell activation in
      response to PAMPs. TLR are type I transmembrane proteins characterized by an
      intracellular Toll/IL 1 receptor homology domain that are expressed by innate
      immune cells (dendritic cells, macrophages, NK cells), cells of the adaptive
      immunity (T and B lymphocytes) and non immune cells (epithelial and endothelial
      cells, fibroblasts). In all the cell types analyzed, TLR agonists, alone or in
      combination with costimulatory molecules, induce cell activation. The crucial
      role played by TLR in immune cell activation has been detailed in dendritic
      cells. A TLR-dependent activation of dendritic cells is required to induce their
      maturation and migration to regional lymph nodes and to activate naive T cells.
      The ability of different cell types to respond to TLR agonists is related to the
      pattern of expression of the TLRs and its regulation as well as their
      intracellular localization. Recent studies suggest that the nature of the
      endocytic and signaling receptors engaged by PAMPs may determine the nature of
      the immune response generated against the microbial molecules, highlighting the
      role of TLRs as molecular interfaces between innate and adaptive immunity. In
      this review are summarized the main biological properties of the TLR molecules.

PMID- 17212935
TI  - [Does FSH signaling have a gender?].
AB  - FSH is the main endocrine control of mammalian reproduction. FSH triggers somatic
      cells of the gonads which support germ cells metabolically, i.e. Sertoli cells of
      the seminiferous tubules, and granulosa cells harboring the oocyte, within the
      ovarian follicle. FSH leads to similar biological responses in both cell types
      since it stimulates proliferation and differentiation, according to the
      developmental stage. However, FSH receptor knock-out female mice are infertile,
      unlike male mice. Hence, FSH is not equally important in both sexes.
      Nevertheless, does FSH induce distinct signalling mechanisms in its target cells
      ? Here, we compare the signalling mechanisms induced by FSH in ovarian and
      testicular physiology.

PMID- 17212936
TI  - [New insight into the treatment of aortic stenosis].
AB  - Aortic valve stenosis (AS) is the most frequent heart disease after coronary
      artery disease and arterial hypertension and it is associated with a high
      incidence of adverse outcomes. Historically, calcific AS has been considered as
      "degenerative" because it was thought to be the result from aging and "wear and
      tear" of the aortic valve. However, this perception has changed over the years
      with the publication of several studies showing that the calcific AS shares many
      histological similarities with atherosclerosis, thus suggesting that this disease
      could eventually be modified by lifestyle or pharmacological therapies.
      Furthermore, recent data support the notion that AS is not an isolated disease
      uniquely limited to the valve. Indeed, AS is frequently associated with
      abnormalities of the systemic arterial system, and in particular with reduced
      arterial compliance, which may have important consequences on the pathophysiology
      and clinical outcome of this disease. Hence, the assessment of AS severity as
      well as its therapeutic management should be conducted with the use of a
      comprehensive evaluation that includes not only the aortic valve but also the
      systemic arterial system and the left ventricle, since these 3 entities are
      tightly intricated on both the pathophysiological and hemodynamic standpoints.

PMID- 17212937
TI  - [Implantable cardioverter defibrillator: an update].
AB  - Automatic implantable cardioverter defibrillator is now a well established
      therapy to prevent sudden cardiac death. In secondary prevention (patients with a
      previous cardiac arrest) defibrillator can be considered as a class I indication,
      if there is no transient or reversible cause. The level of proof is A. in primary
      prevention the defibrillator is indicated in coronary artery disease patients
      with or without symptoms of mild to moderate heart failure (NYHA II or III), an
      ejection fraction lower than 30 %, measured at least one month after a myocardial
      infarction and 3 months after a revascularisation, surgery or angioplasty (level
      of proof B). It is also indicated in symptomatic spontaneous sustained
      ventricular tachycardias with underlying heart disease (level of proof B), in
      patients with spontaneous sustained ventricular tachycardia, poorly tolerated,
      without underlying heart disease for which pharmacological treatment or ablation
      can not be performed or failed (level of proof B). Finally it is also indicated
      in patients with syncope of unknown cause with sustained ventricular tachycardia
      or inducible ventricular fibrillation, with an underlying heart disease (level of
      proof B). The guidelines proposed by the different societies have also proposed
      class IIa recommendations which are the following: coronary artery disease
      patients with left ventricular dysfunction (ejection fraction between 31 or 35 %)
      measured at least one month after a myocardial infarction and 3 months after a
      revascularisation with an inducible ventricular arrhythmia. It can be also
      indicated in idiopathic dilated cardiomyopathies with an ejection fraction lower
      than 30% and NYHA class II or III. It can be also indicated in familial or
      inherited conditions with a high risk of sudden cardiac death by ventricular
      fibrillation without any other efficient known treatment and finally in heart
      failure patients remaining symptomatic, in class III or IV NYHA, with an optimal
      medical therapy, an ejection fraction lower than 35 % and a QRS complex duration
      higher than 120 ms: in this case it is an indication of cardiac resynchronization
      therapy device associated to the defibrillator. All these class IIa indications
      have a level of proof B.

PMID- 17212938
TI  - [The aortic valve did not reveal all its secrets].

PMID- 17212939
TI  - [Premises of the Neanderthal genome].

PMID- 17212940
TI  - [Emerging infectious diseases in Myanmar].

PMID- 17212941
TI  - ["Turning stem cells into cures" or the answer of Arnie to George W].

PMID- 17212942
TI  - [The " rendez-vous" of the European immunologists in Paris].

PMID- 17212943
TI  - [Prevention of mammary tumorigenesis in mice: a hope for the women at risk for
      breast cancer].

PMID- 17212944
TI  - [Gene therapy of junctional epidermolysis bullosa].

PMID- 17212945
TI  - Optimisation of contribution of candidate parents to maximise genetic gain and
      restricting inbreeding using semidefinite programming.
AB  - An approach for optimising genetic contributions of candidates to control
      inbreeding in the offspring generation using semidefinite programming (SDP) was
      proposed. Formulations were done for maximising genetic gain while restricting
      inbreeding to a preset value and for minimising inbreeding without regard of
      gain. Adaptations to account for candidates with fixed contributions were also
      shown. Using small but traceable numerical examples, the SDP method was compared
      with an alternative based upon Lagrangian multipliers (RSRO). The SDP method
      always found the optimum solution that maximises genetic gain at any level of
      restriction imposed on inbreeding, unlike RSRO which failed to do so in several
      situations. For these situations, the expected gains from the solution obtained
      with RSRO were between 1.5-9% lower than those expected from the optimum solution
      found with SDP with assigned contributions varying widely. In conclusion SDP is a
      reliable and flexible method for solving contribution problems.

PMID- 17212946
TI  - Improved techniques for sampling complex pedigrees with the Gibbs sampler.
AB  - Markov chain Monte Carlo (MCMC) methods have been widely used to overcome
      computational problems in linkage and segregation analyses. Many variants of this
      approach exist and are practiced; among the most popular is the Gibbs sampler.
      The Gibbs sampler is simple to implement but has (in its simplest form) mixing
      and reducibility problems; furthermore in order to initiate a Gibbs sampling
      chain we need a starting genotypic or allelic configuration which is consistent
      with the marker data in the pedigree and which has suitable weight in the joint
      distribution. We outline a procedure for finding such a configuration in
      pedigrees which have too many loci to allow for exact peeling. We also explain
      how this technique could be used to implement a blocking Gibbs sampler.

PMID- 17212947
TI  - Bayes factor for testing between different structures of random genetic groups: a
      case study using weaning weight in Bruna dels Pirineus beef cattle.
AB  - The implementation of genetic groups in BLUP evaluations accounts for different
      expectations of breeding values in base animals. Notwithstanding, many feasible
      structures of genetic groups exist and there are no analytical tools described to
      compare them easily. In this sense, the recent development of a simple and stable
      procedure to calculate the Bayes factor between nested competing models allowed
      us to develop a new approach of that method focused on compared models with
      different structures of random genetic groups. The procedure is based on a
      reparameterization of the model in terms of intraclass correlation of genetic
      groups. The Bayes factor can be easily calculated from the output of a Markov
      chain Monte Carlo sampling by averaging conditional densities at the null
      intraclass correlation. It compares two nested models, a model with a given
      structure of genetic groups against a model without genetic groups. The
      calculation of the Bayes factor between different structures of genetic groups
      can be quickly and easily obtained from the Bayes factor between the nested
      models. We applied this approach to a weaning weight data set of the Bruna dels
      Pirineus beef cattle, comparing several structures of genetic groups, and the
      final results showed that the preferable structure was an only group for unknown
      dams and different groups for unknown sires for each year of calving.

PMID- 17212948
TI  - Character process model for semen volume in AI rams: evaluation of correlation
      structures for long and short-term environmental effects.
AB  - The objective of this study was to build a character process model taking into
      account serial correlations for the analysis of repeated measurements of semen
      volume in AI rams. For each ram, measurements were repeated within and across
      years. Therefore, we considered a model including three environmental effects:
      the long-term environmental effect, which is a random year(*)subject effect, the
      short-term environmental effect, which is a random within year
      subject(*)collection effect, and the classical measurement error. We used a four
      step approach to build the model. The first step explored graphically the serial
      correlations. The second step compared four models with different correlation
      structures for the short-term environmental effect. We selected fixed effects in
      the third step. In the fourth step, we compared four correlation structures for
      the long-term environmental effect. The model, which fitted best the data, used a
      spatial power correlation structure for the short-term environmental effect and a
      first order autoregressive process for the long-term environmental effect. The
      heritability estimate was 0.27 (0.04), the within year repeatability decreased
      from 0.56 to 0.44 and the repeatability across years decreased from 0.43 to 0.37.

PMID- 17212949
TI  - Associations of myostatin gene polymorphisms with performance and mortality
      traits in broiler chickens.
AB  - Myostatin is a negative regulator of skeletal muscle growth. We evaluated effects
      of myostatin polymorphisms in three elite commercial broiler chicken lines on
      mortality, growth, feed conversion efficiency, ultrasound breast depth, breast
      percentage, eviscerated carcass weight, leg defects, blood oxygen level, and hen
      antibody titer to infectious bursal disease virus vaccine. Progeny mean data
      adjusted for fixed and mate effects and DNA from 100 sires per line were used.
      Single nucleotide polymorphisms (SNPs) of the myostatin gene segregating in these
      lines were identified by designing specific primers, amplifying individual DNA in
      each line by polymerase chain reaction, cloning, sequencing and aligning the
      corresponding products. Individual sires were genotyped for five identified SNPs
      which contributed to eight haplotypes. Frequencies of SNP alleles and haplotypes
      differed between lines. Using the allele substitution effect model, the myostatin
      SNPs were found to have significant (P < 0.031) associations with growth,
      mortality, blood oxygen and hen antibody titer to infectious bursal disease virus
      vaccine, although the associations were not often consistent across lines. These
      results suggest that the myostatin gene has pleiotropic effects on broiler
      performance.

PMID- 17212950
TI  - Mitochondrial diversity and the origin of Iberian sheep.
AB  - Mitochondrial DNA diversity was analysed in 19 Iberian and six foreign sheep
      breeds. Three mtDNA lineages (B, A and C) were found in the Iberian sheep, with
      type B clearly predominating over the others. The results were analysed for each
      of the morphologically determined breed groups in Iberian sheep: Merino,
      Entrefino, Churro and Iberian trunks. MtDNA lineage C was found only in the
      Iberian trunk composed of Montesina and Ojalada. These two populations had high
      mtDNA variability, and in the Iberian sheep only Merino Branco had more
      variation. The other three Merino types studied showed moderate variability,
      including the most authentic Merino, the Spanish Merino. These three Merinos
      clustered closely in a multidimensional scaling representation of distances,
      while the fourth breed (Merino Branco) showed a clear separation. As for the
      other two trunks, breeds from the Churro group showed greater maternal uniformity
      while results for populations included in the so-called Entrefino trunk seemed to
      have a more heterogeneous maternal origin. The results obtained are discussed
      with available data from nuclear markers and with morphological classifications,
      and all this information is analysed in relation to the origin of the different
      Iberian sheep breeds.

PMID- 17212956
TI  - Epigenetic mechanisms and gastrointestinal development.
AB  - This review considers the hypothesis that nutrition during infancy affects
      developmental epigenetics in the gut, causing metabolic imprinting of
      gastrointestinal (GI) structure and function. Fundamentals of epigenetic gene
      regulation are reviewed, with an emphasis on the epigenetic mechanism of DNA
      methylation. Recent data indicate that transient nutritional and other stimuli
      during critical periods of prenatal and early postnatal development can affect
      the establishment or developmental maturation of gene-specific DNA methylation,
      thereby inducing permanent changes in gene expression. Although epigenetic
      processes are clearly involved in postnatal mammalian GI development, we
      currently know very little about these mechanisms. Data indicating that
      epigenetic gene regulation plays an important role in GI development and
      pathology are reviewed, and suggestions for future research in this area are
      offered.

PMID- 17212960
TI  - Changes in zinc absorption during development.
AB  - Zinc (Zn) nutrition is of special practical importance in infants and young
      children, however relatively little is known about maturation and comparative
      aspects of Zn absorption. The principal objective of this paper is to compare Zn
      absorption of term infants, preterm infants, and adults on low phytate diets.
      Existing data derived from using Zn stable isotopes as extrinsic labels for an
      entire day were modeled with saturation kinetic analysis (saturable response
      model). When adjusted for differences in length of small intestine, the
      efficiency of Zn absorption for both term (4 months) and preterm (33 weeks post
      conception) infants was comparable with that for adults, suggesting early
      maturation of mechanisms that regulate absorption. However, infant intestinal
      lengths were shorter, and Zn absorptive capacity was proportionately less.
      Reduced capacity was matched by lower Zn requirements for normal term infants.
      This favorable match, however, did not occur in the preterm infant because of
      relatively high Zn requirements. Although intestinal conservation of endogenous
      Zn in these preterm infants was appropriate in relation to the quantity of Zn
      absorbed, it was not optimal for achieving the retention required. Normal
      homeostatic mechanisms in the premature infant prevented efficient absorption of
      the quantity of Zn required or/and optimal conservation of endogenous Zn.

PMID- 17212955
TI  - The fetal origins of memory: the role of dietary choline in optimal brain
      development.
AB  - Fetal nutrition sets the stage for organ function in later life. In this review
      we discuss the fetal and neonatal origins of brain function. Numerous research
      observations point to the importance of choline for the developing fetus and
      neonate. This essential nutrient is involved in 1-carbon metabolism and is the
      precursor for many important compounds, including phospholipids, acetylcholine,
      and the methyl donor betaine. Dietary intake of choline by the pregnant mother
      and later by the infant directly affects brain development and results in
      permanent changes in brain function. In rodents, perinatal supplementation of
      choline enhances memory and learning functions, changes that endure across the
      lifespan. Conversely, choline deficiency during these sensitive periods results
      in memory and cognitive deficits that also persist. Furthermore, recent studies
      suggest that perinatal choline supplementation can reduce the behavioral effects
      of prenatal stress and the cognitive effects of prenatal alcohol exposure in
      offspring. The likely mechanism for these effects of choline involves DNA
      methylation, altered gene expression, and associated changes in stem cell
      proliferation and differentiation. The currently available animal data on choline
      and hippocampal development are compelling, but studies are needed to determine
      whether the same is true in humans.

PMID- 17212966
TI  - Superheated water extraction and phase transfer methylation of phenoxy acid
      herbicides from solid matrices.
AB  - Phase transfer catalytic methylation was applied to directly derivatise
      chlorophenoxy acid herbicides in superheated water extracts from sand and soil
      samples. The extractions were carried out at 120 degrees C statically for 5 min
      and then dynamically for 10 min at 1.0 mL min(-1) using water at pH 11.0 for a
      sand matrix and a flow rate of 0.5 mL min(-1) at pH 7.0 for soil samples. The
      methylation was carried out on-line on the extraction solution with
      ultrasonication at 80 degrees C, using either 0.05 mmol tetrabutylammonium
      bromide (TBAB) or 0.0125 mmol cetyltrimethylammonium bromide (CTAB) as phase
      transfer catalysts with 0.20 mmol methyl iodide in 2.0 mL dichloromethane
      trapping solvent. The former catalyst provided a higher yield but the latter gave
      fewer interfering peaks. The recoveries of most chlorophenoxy acids using the
      TBAB catalyst ranged from 67 to 105% for sand and from 82 to 114% for soil
      sample, except phenoxyacetic acid, 2-(2, 4-dichlorophenoxy)propanoic acid and 1
      naphthaleneacetic acid, while those by using CTAB were slightly lower. Detection
      limits of all the analytes extracted from sand using TBAB catalyst were in a
      range of 5.3-16 microg g(-1) analysed by using gas chromatography with flame
      ionization detection (GC-FID).

PMID- 17212967
TI  - The heat stability of Plasmodium lactate dehydrogenase-based and histidine-rich
      protein 2-based malaria rapid diagnostic tests.
AB  - Malaria rapid diagnostic tests (RDTs) have performed well in a variety of
      studies, but recent reports have described sensitivity for Plasmodium falciparum
      as significantly lower than that required for operational deployment. Exposure to
      high temperature has been suggested as an explanation. This study assessed the
      temperature stability of two different Plasmodium lactate dehydrogenase (pLDH)-
      and three histidine-rich protein 2 (HRP2)-detecting RDTs. One HRP2 test proved
      insufficiently sensitive for assessment. After incubation at 35, 45 and 60
      degrees C, two RDTs detecting pLDH showed a substantial fall in percentage test
      line positivity over time, which was not seen with the remaining two HRP-2-based
      RDTs. For the particular products studied, variability was high, with the pLDH
      based RDTs being less sensitive than HRP2-based RDTs against the sample of P.
      falciparum used and more susceptible to heat-induced damage, but the reasons for
      this are unclear. The performance of malaria RDTs can be adversely affected at
      the temperatures to which they will be exposed when transported to, and used in,
      the rural tropics.

PMID- 17212968
TI  - Maternal hyperthermia disrupts developmental competence of follicle-enclosed
      oocytes: in vivo and ex vivo studies in mice.
AB  - Mammalian oocytes are susceptible to thermal stress at various stages of
      follicular development. We examined whether the ovarian pool of oocytes is
      susceptible to maternal hyperthermia and if so, whether hyperthermia at the
      germinal vesicle (GV) stage further affects the developmental competence of
      preimplantation embryos and offspring quality. Synchronized female mice were
      exposed to thermal stress (40 degrees C, 65% RH) for 1.5-2h or maintained under
      normothermal conditions (25 degrees C, 45% RH). Thereafter, mice were paired with
      stud males. In the first experiment, mated mice were sacrificed 20h post hCG
      administration, and in vivo-derived zygotes were recovered and cultured in vitro.
      Maternal hyperthermia decreased the percentage of putative zygotes of apparent
      normal morphology in the heat-stressed group (81+/-1.3%) as compared to the
      control group (86+/-1.2%). Developmental competence was also compromised as
      expressed by the disruption in cleavage timing pattern, resulting in a reduced
      developmental rate to the blastocyst stage (57+/-2.6% versus 84+/-1.9%). In the
      second experiment, both groups were left with stud males until litter delivery.
      Litter size in the first delivery cycle was lower for the heat-stressed group
      (7.7+/-1.1 pups), followed by a slight increase throughout consecutive cycles as
      compared to the control group (11.3+/-1.0 pups). Behavioral examinations of 8
      week-old pups revealed similar locomotor activity and learning potential between
      the groups. In summary, the findings indicate that a subpopulation of the ovarian
      pool of follicles is highly sensitive to thermal stress and that maternal
      hyperthermia disrupts developmental competence of GV-stage oocytes. Pups that
      developed from oocytes that survived thermal stress exhibited a developmental
      potential similar to that of the of control pups.

PMID- 17212969
TI  - Hydromechanics in dentine: role of dentinal tubules and hydrostatic pressure on
      mechanical stress-strain distribution.
AB  - OBJECTIVES: This investigation is to understand the role of free water in the
      dentinal tubules on the mechanical integrity of bulk dentine. METHODS: Three
      different experiments were conducted in this study. In experiment 1, three
      dimensional models of dentine with gradient elastic modulus, homogenous elastic
      modulus, and with and without hydrostatic pressure were simulated using the
      finite element method. Static compressive loads of 15, 50 and 100 N were applied
      and the distribution of the principal stresses, von Mises stresses, and strains
      in loading direction were determined. In experiment 2, experimental compression
      testing of fully hydrated and partially dehydrated dentine (21 degrees C for 72
      h) was conducted using a Universal testing machine. In experiment 3, Fourier
      transform infrared spectroscopic analysis of hydrated and partially dehydrated
      dentine was carried out. RESULTS: The finite element analysis revealed that the
      dentine model with simulated hydrostatic pressure displayed residual tensile
      stresses and strains in the inner region adjacent to the root canal. When
      external compressive loads were applied to the model, the residual stresses and
      strains counteracted the applied loads. Similarly the hydrated specimens
      subjected to experimental compression loads showed greater toughness when
      compared to the partially dehydrated specimens. The stress at fracture was
      significantly higher in partially dehydrated specimens (p=0.014), while the
      strain at fracture was significantly higher in hydrated dentine specimens
      (p=0.037). SIGNIFICANCE: These experiments highlighted the distinct role of free
      water in the dentinal tubules and hydrostatic pressure on the stress-strain
      distribution within the bulk dentine.

PMID- 17212970
TI  - Children's experiences of violence: some have much more than others.

PMID- 17212971
TI  - Therapeutic time window of post-ischemic mild hypothermia and the gene expression
      associated with the neuroprotection in rat focal cerebral ischemia.
AB  - Hypothermia is the only neuroprotective therapy proven to be clinically
      effective. Identifying the molecules that play important roles in the efficacy of
      hypothermia, we developed a multi-channel computer-controlled system, in which
      the brain temperatures of freely moving rats were telemetrically monitored and
      maintained below 35 degrees C, and examined the time window necessary to exert
      its significant neuroprotective effects. Eight-week-old SD rats were subjected to
      a 2h middle cerebral artery occlusion (MCAO) with an intraluminal filament, and
      post-ischemic hypothermia was introduced at 0, 2, 4, or 6h after reperfusion
      until the rats were killed 2 days after MCAO. Since a significant protection was
      observed when hypothermia was started within 4h after reperfusion, it was
      concluded that the therapeutic time window of mild hypothermia lasts for 4h after
      reperfusion in our model. On the basis of the window, comprehensive gene
      expression analyses using oligonucleotide microarrays were conducted and
      identified potential genes related to the efficacy of hypothermia, which included
      inflammatory genes like osteopontin, early growth response-1, or macrophage
      inflammatory protein-3alpha. Therefore, the neuroprotective effects of post
      ischemic mild hypothermia were strongly suggested to be mainly associated with
      the reduction of neuronal inflammation.

PMID- 17212972
TI  - Entrapment in E. coli improves the operational stability of recombinant beta
      glycosidase CelB from Pyrococcus furiosus and facilitates biocatalyst recovery.
AB  - beta-Glycosidase CelB from the hyperthermophilic archaeon Pyrococcus furiosus is
      a versatile biocatalyst that has been used for the hydrolysis and synthesis of
      beta-d-glycosidic compounds at high temperatures and in non-conventional
      solvents. In spite of its outstanding thermal stability, CelB is prone to
      inactivation in the presence of reducing sugars and through recirculation in loop
      enzyme reactors. Entrapment into E. coli cells was used here to improve the
      stability of recombinant CelB under conditions promoting strong inactivation.
      Glutardialdehyde-mediated protein cross-linking or rigidification of the cell
      membrane by adding magnesium ions was required to prevent release of CelB from
      within the cell into the bulk solution. In the presence of 1M glucose or when
      applying recirculation rates of 2.6 min(-1), the entrapped enzyme was around two
      fold more stable at 80 degrees C than free CelB. The significance of the
      stabilisation was attenuated by the decrease in CelB initial activity which was
      due to cross-linking and glutardialdehyde concentration-dependent. Entrapment
      facilitated downstream processing of CelB and biocatalyst recovery in repeated
      batchwise conversions of lactose at elevated temperatures.

PMID- 17212973
TI  - Neuropeptide Y can rescue neurons from cell death following the application of an
      excitotoxic insult with kainate in rat organotypic hippocampal slice cultures.
AB  - In the present work we investigated the neuroprotective role of neuropeptide Y
      (NPY) after an excitotoxic insult in rat organotypic hippocampal slice cultures.
      Exposure of 2 week-old rat hippocampal slice cultures to 12muM kainate (KA) for
      24h induced neuronal death in dentate gyrus (DG) granular cell layer, CA1 and CA3
      pyramidal cell layers, as quantified by cellular propidium iodide (PI) uptake.
      The activation of Y(1) or Y(2) receptors 30min after starting the exposure to the
      excitotoxic insult with kainate resulted in neuroprotection by reducing the PI
      uptake in DG, CA1 and CA3 cell layers. The use of Y(1) or Y(2) receptors
      antagonists, BIBP3226 (1muM) or BIIE0246 (1muM), resulted in the loss of the
      neuroprotection induced by the activation of Y(1) or Y(2) receptors,
      respectively, in all hippocampal subfields. Taken together these results suggest
      that activation of NPY Y(1) or Y(2) receptors activates neuroprotective pathways
      that are able to rescue neurons from excitotoxic cell death.

PMID- 17212974
TI  - Rhabdomyolysis of the masseter muscle: case report.
AB  - We describe a case of rhabdomyolysis involving the masseter muscle. It involved
      an episode of muscle lysis of the left upper and lower limb and the left
      masseter, after ingesting an unknown quantity of alcohol, amphetamines and
      ecstasy with prolonged immobility for an unknown period after collapse.
      Musculoskeletal sonography was used to diagnose rhabdomyolysis of the left
      masseter muscle.

PMID- 17212975
TI  - Scorpion digestive lipase: a member of a new invertebrate's lipase group
      presenting novel characteristics.
AB  - Unlike classical digestive lipases, the scorpion digestive lipase (SDL) has a
      strong basic character. The SDL activity's optimal pH, when using tributyrin or
      olive oil as substrate, was 9.0. Added to that, the estimated isoelectric point
      of the native SDL using the electrofocusing technique, was found to be higher
      than 9.6. To our knowledge, this is the first report of an animal digestive
      lipase having such a basic character. When olive oil was used as substrate, SDL
      was shown to be insensitive to the presence of amphiphilic proteins such as
      bovine serum albumin (BSA). Furthermore, the hydrolysis was found to be
      specifically dependent on the presence of Ca(2+) ions, since no significant SDL
      activity was detected in the presence of ions chelator such as EDTA.
      Nevertheless, the SDL does not require Ca(2+) to trigger the hydrolysis of
      tributyrin emulsion. Interestingly Zn(2+) and Cu(2+) ions act as strong
      inhibitors of SDL activity when using tributyrin as substrate. An internal
      chymotryptic cleavage of SDL generated two fragments of 28 and 25 kDa having the
      same N-terminal sequence. This sequence of 19 residues does not share any
      homology with known animal and microbial lipases. Polyclonal antibodies directed
      against SDL (pAbs anti-SDL) failed to recognise ostrich pancreatic and dog
      gastric lipases (OPL and rDGL). Moreover, both pAbs anti-OPL and anti-rDGL failed
      to immunoreact with SDL. These immunological as well as distinct biochemical
      properties strengthen the idea that SDL appears to belong to a new invertebrate's
      lipase group.

PMID- 17212976
TI  - Compromising bradycardia: management in the emergency department.
AB  - AIM OF THE STUDY: Bradycardia may represent a serious emergency. The need for
      temporary and permanent pacing is unknown. METHODS: We analysed a registry for
      the incidence, symptoms, presenting rhythm, underlying mechanism, management and
      outcome of patients presenting with compromising bradycardia to the emergency
      department of a university hospital retrospectively during a 10-year period.
      RESULTS: We identified 277 patients, 173 male (62%), median age 68 (IQR 58-78),
      median ventricular rate 33 min(-1) (IQR 30-40). The leading symptoms were syncope
      [94 (33%)], dizziness [61 (22%)], collapse [46 (17%)], angina [46 (17%)] and
      dyspnoea/heart failure [30 (11%)]. The initial ECG showed high grade AV block
      [134 (48%)], sinus bradycardia/AV block [46 (17%)], sinuatrial arrest [42 (15%)],
      bradycardic atrial fibrillation [39 (14%)] and pacemaker-failure [16 (6%)]. The
      underlying mechanisms were primary disturbance of cardiac automaticity and/or
      conduction [135 (49%)], adverse drug effect [58 (21%)], acute myocardial
      infarction [40 (14%)], pacemaker failure [16 (6%)], intoxication [16 (6%)] and
      electrolyte disorder [12 patients (4%)]. In 107 (39%) patients bed rest resolved
      the symptoms. Intravenous drugs to increase ventricular rate were given to 170
      (61%) patients, 54 (20%) required additional temporary transvenous/transcutaneous
      pacing. Two severely intoxicated patients could be stabilised only by
      cardiopulmonary bypass. A permanent pacemaker was implanted in 137 patients
      (50%). Mortality was 5% at 30 days. CONCLUSION: In our cohort, about 20% of the
      patients presenting with compromising bradycardia required temporary emergency
      pacing for initial stabilisation, in 50% permanent pacing had to be established.

PMID- 17212977
TI  - Removal of small trihalomethane precursors from aqueous solution by
      nanofiltration.
AB  - The removal of small trihalomethane precursors (THMPs) from aqueous solution by
      two commercial nanofiltration membranes (NF70 and NF270) was investigated.
      Resorcinol, phloroglucinol, and 3-hydroxybenzoic acid were selected as model
      compounds of small THMPs, while tannic acid was chosen as a medium molecular
      disinfection by-product (DBP) precursor for comparison. The performance of
      nanofiltration membranes were evaluated by introducing polyethylene glycol (PEG)
      solutions and uncharged saccharides to estimate molecular weight cut-off (MWCO)
      and membrane pore radii, respectively. The streaming potential was measured to
      estimate the membrane surface charge at different pH values, which reveals that
      the NF270 membrane is more pH-sensitive than the NF70 membrane. The rejections of
      the above selected THMPs were assessed under various pH values, and the removal
      efficiencies of THMPs for both membranes at high pH values are reasonably well.
      Charge exclusion is the prevailing mechanism for the selected small model
      compounds retended by the negatively charged nanofiltration membranes, while size
      exclusion and adsorption are controlled mechanisms but not sufficient for the
      rejection of unionized small organic molecules. In general, the NF270 membrane
      exhibits the superior permeation rate value, which takes an advantage over the
      NF70 membrane from the aspect of energy conservation.

PMID- 17212978
TI  - Germinal vesicle chromatin configuration and meiotic competence is related to the
      oocyte source in canine.
AB  - This study investigated the effect of deriving oocytes from different stages of
      the estrous cycle on oocyte diameter, germinal vesicle (GV) chromatin
      configuration, and in vitro meiotic competence in canine oocytes. Cumulus oocyte
      complexes (COCs) were recovered from both ovaries during anestrous, follicular,
      and luteal phases and in vivo ovulated oocytes. The diameter of canine oocyte was
      compared with or without the zona pellucida (ZP) before in vitro maturation
      (IVM). Also, GV chromatin configuration was evaluated before (0 h) or 72 h after
      IVM by fixation with 3.7% formaldehyde supplemented with 10 microg/ml Hoechst
      33342 for 30 min. COCs were matured in TCM199 supplemented with 10% fetal bovine
      serum (FBS), 0.6 mM cysteine, 0.2 mM pyruvic acid, 50 microg/ml gentamycin
      sulfate, and 20 microg/ml 17beta-estradiol (E(2)) at 39 degrees C and 5% CO(2) in
      air for 72 h. The diameter of in vivo ovulated oocytes with the ZP (167.5+/-12.7
      microm) or without ZP (133.9+/-5.3 microm) was significantly greater (p<0.05)
      than those of anestrous, follicular, and luteal oocytes (with ZP, 151.2+/-7.4,
      153.1+/-8.8 and 152.8+/-5.4 microm, respectively; without ZP, 115.3+/-7.6,
      122.1+/-4.9 and 114.3+/-6.6 microm, respectively). At 0 h, the GV-II
      configuration was more prevalent in oocytes from anestrual ovaries than from
      follicular or luteal ovaries or in vivo ovulated oocytes (63.6% versus 14.8%,
      33.0%, and 0.0%; p<0.05), whereas the proportion of oocytes with the GV-V
      configuration was higher in follicular phase and ovulated oocytes than in oocytes
      from anestrus and luteal phase (57.4% and 100% versus 2.0% and 22.7%; p<0.05).
      However, oocytes in luteal phase exhibited diverse GV configurations (10.3%,
      33.0%, 16.5%, 13.4%, and 22.7% in GV-I, GV-II, GV-III, GV-IV, and GV-V,
      respectively). After 72 h post-IVM, a greater percentage of in vivo ovulated
      oocytes progressed to MII than those oocytes collected during anestrous,
      follicular, and luteal phases (50.0% versus 5.5%, 11.5%, and 9.1%; p<0.05). In
      conclusion, the oocyte diameter, GV chromatin configuration, and meiotic
      maturation of canine COCs are related to the oocyte source. These results
      indicated that the oocyte source could be critical to nuclear progression to MII
      stage in canines.

PMID- 17212979
TI  - Development of vitrified-thawed bovine oocytes after in vitro fertilization and
      somatic cell nuclear transfer.
AB  - Cryopreservation could be a useful technique for providing a steady source of
      oocytes for nuclear transfer and in vitro embryo production. The purpose of this
      study was to develop a method for cryopreservation of bovine oocytes while
      maintaining the developmental potential following subsequent in vitro
      fertilization (IVF) or somatic cell nuclear transfer (SCNT). Following
      vitrification-thawing, the surviving oocytes were (a) used for parthenogenetic
      activation, (b) examined for pronuclear formation after IVF, (c) examined for
      embryo development after IVF, and (d) used for SCNT employing fetal fibroblasts
      transfected with green fluorescent protein (GFP) gene. While most of the oocytes
      survived vitrification when the microdrop method was used (92.50%), the cleavage
      and blastocyst formation rates after parthenogenetic activation were lower (46.5%
      and 11.1%) than that in the non-vitrified control (86.6% and 13.5%). After IVF,
      the pronuclear formation (2PN) of fertilized embryos was lower in the vitrified
      group than in the control (21.7% and 59.9%). After SCNT, fusion rates were
      similar in control (58.33%) and vitrified-thawed oocytes (53.19%). However, the
      cleavage (73.1% and 46.3%) and blastocyst formation rates (22.2%, 7.4%; p<0.05)
      differed between control and vitrified-thawed oocytes. In vitrified-thawed or
      control oocytes, all embryos reconstructed using fetal fibroblasts transfected
      with GFP gene showed GFP expression. To evaluate the complete developmental
      potential, embryos derived from vitrified-thawed and fresh control oocytes were
      non-surgically transferred to 27 recipients (16 for control and 11 for vitrified
      thawed). In the vitrified-thawed group, two pregnancies were detected at day 60,
      and one of them lasted until day 222. While in the fresh group, one pregnancy
      maintained to term. In conclusion, vitrified-thawed bovine oocytes could support
      development into the subsequent stages after IVF and SCNT. In addition, this
      study showed the possibility of the vitrified-thawed bovine oocytes in the
      production of transgenic cloned animals. In addition, further studies are
      required to increase the efficiency of oocyte vitrification for the practical
      uses and production of live offspring.

PMID- 17212980
TI  - Response to GnRH on day 6 of the estrous cycle is diminished as the percentage of
      Bos indicus breeding increases in Angus, Brangus, and Brahman x Angus heifers.
AB  - Angus (n=6), Brangus (5/8 Angus x 3/8 Brahman, n=6), and Brahman x Angus (3/8
      Angus x 5/8 Brahman, n=6) heifers exhibiting estrous cycles at regular intervals
      were used to determine if the percentage of Bos indicus breeding influenced the
      secretory patterns of LH in response to a GnRH treatment on Day 6 of the estrous
      cycle. Heifers were pre-synchronized with a two-injection PGF(2 alpha) protocol
      (25 mg i.m. Day -14 and 12.5 mg i.m. Day -3 and -2 of experiment). Heifers
      received 100 microg GnRH i.m. on Day 6 of the subsequent estrous cycle. Blood
      samples were collected at -60, -30, and -1 min before GnRH and 15, 30, 60, 90,
      120, 150, 180, 240, 300, 360, 420, and 480 min after GnRH to determine
      concentrations of serum LH. Estradiol concentrations were determined at -60, -30,
      and -1 min before GnRH. On Day 6 and 8, ovaries were examined by ultrasonography
      to determine if ovulation occurred. On Day 13, heifers received 25 mg PGF(2
      alpha) i.m. and blood samples were collected daily until either the expression of
      estrus or Day 20 for heifers not exhibiting estrus to determine progesterone
      concentrations. There was no effect (P>0.10) of breed on ovulation rate to GnRH
      as well as size of the largest follicle, mean estradiol, and mean corpus luteum
      volume at GnRH. Mean LH was greater (P<0.05) for Angus (7.0+/-0.8 ng/mL) compared
      to Brangus (4.6+/-0.8 ng/mL) and Brahman x Angus (2.9+/-0.8 ng/mL), which were
      similar (P>0.10). Mean LH peak-height was similar (P>0.10) for Brangus (13.9+/
      3.4 ng/mL) compared to Angus (21.9+/-3.4 ng/mL) and Brahman x Angus (8.0+/-3.4
      ng/mL), but was greater (P<0.05) for Angus compared to Brahman x Angus. Interval
      from GnRH to LH peak was similar (P>0.10) between breeds. As the percentage of
      Bos indicus breeding increased the amount of LH released in response to GnRH on
      Day 6 of the estrous cycle decreased.

PMID- 17212981
TI  - Construction of anti-EGFR immunoliposomes via folate-folate binding protein
      affinity.
AB  - A novel method for synthesis of anti-EGFR immunoliposomes using folate-folate
      binding protein (FBP) affinity is described. An anti-EGFR antibody (cetuximab or
      C225) was covalently linked to FBP via a thioether bond. Liposomes incorporating
      a lipophilic folate derivative (folate-PEG-cholesterol) were prepared by
      polycarbonate membrane extrusion. Anti-EGFR immunoliposomes were then obtained by
      combining FBP-C225 and folate-liposomes and evaluated for uptake and cytotoxicity
      in EGFR-overexpressing U87 human glioblastoma cells. Anti-EGFR immunoliposomes
      constructed via folate-FBP affinity exhibited excellent stability under
      physiological pH, and quickly released the bound FBP-C225 upon low pH (pH 3.5)
      treatment. Flow cytometry and fluorescence microscopy showed similar receptor
      specific binding and internalization for both folate-FBP affinity-coupled and
      covalently coupled C225-immunoliposomes, but not for the non-targeted IgG
      immunoliposomes. C225-immunoliposomes loaded with anticancer drug doxorubicin
      were more cytotoxic than non-targeted immunoliposomes in EGFR-overexpressing U87
      glioma cells. Folate-FBP affinity is a potential method for construction of
      immunoliposomes and may have applications in synthesis of targeted drug carriers
      in general.

PMID- 17212982
TI  - Association analysis of sphingomyelinase 2 polymorphisms for the extrinsic type
      of atopic dermatitis in Koreans.

PMID- 17212983
TI  - Amperometric glucose biosensor based on multilayer films via layer-by-layer self
      assembly of multi-wall carbon nanotubes, gold nanoparticles and glucose oxidase
      on the Pt electrode.
AB  - A novel amperometric glucose biosensor based on the nine layers of multilayer
      films composed of multi-wall carbon nanotubes (MWCNTs), gold nanoparticles (GNp)
      and glucose oxidase (GOD) was developed for the specific detection of glucose.
      MWCNTs were chemically modified with the H(2)SO(4)-HNO(3) pretreatment to
      introduce carboxyl groups which were used to interact with the amino groups of
      poly(allylamine) (PAA) and cysteamine via 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide/N-hydroxysuccinimide cross-linking reaction, respectively. A cleaned
      Pt electrode was immersed in PAA, MWCNTs, cysteamine and GNp, respectively,
      followed by the adsorption of GOD, assembling the one layer of multilayer films
      on the surface of Pt electrode (GOD/GNp/MWCNTs/Pt electrode). Repeating the above
      process could assemble different layers of multilayer films on the Pt electrode.
      PBS washing was applied at the end of each assembly deposition for dissociating
      the weak adsorption. Film assembling and characterization were studied by
      transmission electron microscopy and quartz crystal microbalance, and properties
      of the resulting glucose biosensors were measured by electrochemical
      measurements. The marked electrocatalytic activity of Pt electrode based on
      multilayer films toward H(2)O(2) produced during GOD enzymatic reactions with
      glucose permitted effective low-potential amperometric measurement of glucose.
      Taking the sensitivity and selectivity into consideration, the applied potential
      of 0.35 V versus Ag/AgCl was chosen for the oxidation detection of H(2)O(2) in
      this work. Among the resulting glucose biosensors, the biosensor based on nine
      layers of multilayer films was best. It showed a wide linear range of 0.1-10mM
      glucose, with a remarkable sensitivity of 2.527 microA/mM, a detection limit of
      6.7 microM estimated at a signal-to-noise ratio of 3 and fast response time
      (within 7s). Moreover, it exhibited good reproducibility, long-term stability and
      the negligible interferences of ascorbic acid, uric acid and acetaminophen. The
      study can provide a feasible approach on developing new kinds of oxidase-based
      amperometric biosensors, and can be used as an illustration for constructing
      various hybrid structures.

PMID- 17212984
TI  - Pulmonary arterial reactivity during induced infection of single lung allografts.
AB  - OBJECTIVE: Infection is a major cause of mortality in the first year following
      single lung transplantation and is a distinct risk factor for the development of
      obliterative bronchiolitis. However, little is known about changes in pulmonary
      vascular activity in the setting of infection, which might affect and limit
      function of the graft. Therefore, the aim of this study was to determine how
      acute infection altered pulmonary arterial reactivity in single lung allografts.
      Such information could help to develop better diagnostic and therapeutic targets
      to improve outcome when grafts become infected. METHODS: Following single lung
      transplantation, dogs were immunosuppressed with methylprednisolone acetate,
      cyclosporine and azathioprine. On postoperative day 5, infection was induced in
      one group of dogs by endobronchial inoculation of antibiotic resistant Eschericia
      coli (infection group, n=5); in the second group, the same amount of culture
      media without bacteria was flushed into the bronchus (control group, n=4). All
      animals were medicated under the same drug protocol. On postoperative day 8,
      lungs were removed, reviewed for histological assessment, pulmonary arteries were
      isolated, cut into rings and suspended for pharmacological characterization in
      organ chambers. RESULTS: With acute infections, contractions to phenylephrine and
      angiotensin-1, but not endothelin-1, were reduced in pulmonary arteries with but
      not without endothelium. Inhibition of nitric oxide synthase with N(G)-monomethyl
      L-arginine, monoacetate salt (L-NMMA) restored these contractions. Endothelium
      dependent relaxations to adenosine diphosphate and calcium ionophore, which
      stimulate release of endothelium-derived nitric oxide by a receptor and non
      receptor mediated process, respectively, were not different between groups.
      Relaxations to nitric oxide also were not different between groups. CONCLUSION:
      These results suggest that acute infection selectively reduces contractions of
      pulmonary arteries in part through receptor-mediated release of nitric oxide from
      the endothelium. Inhibiting nitric oxide during episodes of acute infection may
      help to improve graft perfusion during episodes of acute infection.

PMID- 17212985
TI  - The macrophage chemotactic activity of Streptococcus agalactiae and Streptococcus
      iniae extracellular products (ECP).
AB  - The ability of Streptococcus agalactiae and Streptococcus iniae to attract
      macrophages of Nile tilapia (Oreochromis niloticus) was investigated. The
      extracellular products (ECP) from S. agalactiae and S. iniae were tested in vitro
      for macrophage chemotaxis using blind-well chambers. The macrophages were
      obtained from the peritoneal cavity 4-5 days after intraperitoneal injection of
      squalene. Both macrophage chemotactic and chemokinetic activities were
      demonstrated using the S. agalactiae ECP. However, only chemotactic activity was
      shown for S. iniae ECP. High-pressure liquid chromatography fractionation
      revealed that semi-purified S. agalactiae and S. iniae ECPs had estimated
      molecular weights of 7.54 and 19.2kDa, respectively. The prominent chemotactic
      activities of ECP from S. agalactiae and S. iniae are likely to be involved in
      the proinflammatory responses of macrophages to S. agalactiae and S. iniae
      infections.

PMID- 17212986
TI  - Fold-recognition and comparative modeling of human beta3GalT I, II, IV, V and VI
      and beta3GalNAcT I: prediction of residues conferring acceptor substrate
      specificity.
AB  - beta3GalTs are type II transmembrane proteins that transfer galactose from UDP
      Gal donor substrate to acceptor GlcNAc, GalNAc or Gal in beta1-->3-linkage. beta1
      ->3-linked galactose have been found to be a part of many glycans like
      glycosphingolipids, core tetrasaccharide of proteoglycans, type 1 chains. The 3-D
      structure of none of the beta3GalTs is known to date. In this study, the 3-D
      structures of human beta3GalT I, II, IV, V, VI and beta3GalNAcT I have been
      modeled using fold-recognition and comparative modeling methods. Residues that
      constitute the UDP-Gal binding site have been predicted. The models are able to
      qualitatively rationalize data from the site-directed mutagenesis experiments
      reported in the literature. Residues likely to be involved in conferring
      differential acceptor substrate specificity have been predicted by a combination
      of specificity determining positions prediction (SDPs) and subsequent mapping on
      the generated 3-D models.

PMID- 17212987
TI  - Infectious keratitis following keratoplasty.
AB  - Infectious keratitis following corneal transplantation is one of the leading
      causes of failure of a corneal graft. The incidence of graft infection is
      variable, with developing countries having a higher incidence. The majority of
      the graft infections occur within 1 year of the corneal transplantation. Suture
      related problems and persistent epithelial defect are the most common risk
      factors predisposing to graft infection. Pneumococcus species and Staphylococcus
      aureus have been found to be the commonest microorganisms in the developed world,
      whereas Staphylococcus epidermidis is the most often detected microorganism in
      corneal graft infection in the developing world. The early identification of
      predisposing risk factors in patients and their appropriate management at the
      earliest may prevent the occurrence of graft infection and might improve graft
      survival. Visual prognosis in eyes with post-keratoplasty graft infection is poor
      even after optimal therapy and there is a high rate of graft decompensation.

PMID- 17212988
TI  - Botulinum toxin in ophthalmology.
AB  - Since its introduction into clinical medicine in 1980, botulinum toxin has become
      a major therapeutic drug with applications valuable to many medical sub
      specialties. Its use was spearheaded in ophthalmology where its potential
      applications have expanded to cover a broad range of visually related disorders.
      These include dystonic movement disorders, strabismus, nystagmus, headache
      syndromes such as migraine, lacrimal hypersecretion syndromes, eyelid retraction,
      spastic entropion, compressive optic neuropathy, and, more recently, periorbital
      aesthetic uses. Botulinum toxin is a potent neurotoxin that blocks the release of
      acetylcholine at the neuromuscular junction of cholinergic nerves. When used
      appropriately it will weaken the force of muscular contraction, or inhibit
      glandular secretion. Recovery occurs over 3 to 4 months from nerve terminal
      sprouting and regeneration of inactivated proteins necessary for degranualtion of
      acetylcholine vesicles. Complications are related to chemodenervation of adjacent
      muscle groups, injection technique, and immunological mechanisms.

PMID- 17212990
TI  - Congenital corneal anesthesia.
AB  - Congenital corneal anesthesia is a rare clinical entity that poses a diagnostic
      dilemma, particularly in the pediatric age group. The sensory deficit may be
      confined to the cornea, or extend to other divisions of the trigeminal nerve. The
      sensory deficit may occur as an isolated abnormality, as part of a complex
      neurological syndrome, or it may occur in association with multiple somatic
      abnormalities and congenital insensitivity to pain. This condition usually
      presents between the ages of 8 to 12 months. Poor vision, photophobia,
      conjunctival injection, and corneal ulceration in the absence of pain and
      distress in a child should alert the clinician to the possibility of anesthetic
      cornea. In the early stages of presentation, punctuate keratopathy is the main
      feature, which may progress to non-healing persistent corneal epithelial defects.
      This stage may progress to acute corneal lysis and perforation. In most patients,
      conservative approaches such as copious lubrication, prevention of self-harm and
      cautious use of bandage contact lenses are effective in preventing progressive
      corneal damage. Tarsorrhapy is effective in promoting epithelial healing and
      permanent lateral tarsorraphy may prevent further development of epithelial
      defects. Amniotic membrane graft may be considered in order to improve epithelial
      healing. Corneal grafts carry a poor prognosis. Accurate initial diagnosis,
      evaluation, and proper management are paramount to prevent visual loss due to
      long-term complications of corneal anesthesia. This review of the literature
      outlines the problems and approaches in diagnosis, evaluation, and management of
      this rare condition.

PMID- 17212991
TI  - The clinical applications of multifocal electroretinography: a systematic review.
AB  - Multifocal electroretinography (mfERG) is an investigation that can
      simultaneously measure multiple electroretinographic responses at different
      retinal locations by cross-correlation techniques. mfERG therefore allows
      topographic mapping of retinal function in the central 40-50 degrees of the
      retina. The strength of mfERG lies in its ability to provide objective assessment
      of the central retinal function at different retinal areas within a short
      duration of time. Since the introduction of mfERG in 1992, mfERG has been applied
      in a large variety of clinical settings. This article reviews the clinical
      applications of mfERG based on the currently available evidence. mfERG has been
      found to be useful in the assessment of localized retinal dysfunction caused by
      various acquired or hereditary retinal disorders. The use of mfERG also enabled
      clinicians to objectively monitor the treatment outcomes as the changes in visual
      functions might not be reflected by subjective methods of assessment. By changing
      the stimulus, recording, and analysis parameters, investigation of specific
      retinal electrophysiological components can be performed topographically. Further
      developments and consolidations of these parameters will likely broaden the use
      of mfERG in the clinical setting.

PMID- 17212989
TI  - Optic disk size and glaucoma.
AB  - Assessment of optic disk size is an important, but often overlooked, component of
      the diagnostic evaluation for glaucoma. Measured values of optic disk size vary
      with the measurement technique utilized. Available methods for disk size
      measurement and their respective strengths and limitations will be discussed.
      Further, actual disk size varies with race and possibly other demographic
      characteristics. Disk size is also associated with variation of specific
      anatomical structures of the optic nerve head and the retinal nerve fiber layer.
      These disk size- dependent variations may influence the susceptibility to
      glaucoma or the likelihood of glaucoma diagnosis. This manuscript reviews the
      published evidence relating to disk size and glaucoma.

PMID- 17212993
TI  - Optic neuritis is nothing to sneeze at.
AB  - A 36-year-old man developed acute visual loss, mimicking an optic neuritis in the
      left eye. Cranial magnetic resonance imaging revealed a sphenoid sinus mucocele
      with extension into the anterior clinoid process abutting the left optic nerve.
      Endoscopic marsupialization of the mucocele led to marked improvement of vision.
      Sphenoid sinus mucocele is discussed, as is the differential diagnosis of optic
      neuritis.

PMID- 17212992
TI  - Ophthalmic manifestations and histopathology of infantile nephropathic
      cystinosis: report of a case and review of the literature.
AB  - Cystinosis is a rare autosomal recessive metabolic disorder characterized by the
      intracellular accumulation of cystine, the disulfide of the amino acid cysteine,
      in many organs and tissues. Infantile nephropathic cystinosis is the most severe
      phenotype. Corneal crystal accumulation and pigmentary retinopathy were
      originally the most commonly described ophthalmic manifestations, but successful
      kidney transplantation significantly changed the natural history of the disease.
      As cystinosis patients now live longer, long-term complications in extrarenal
      tissues, including the eye, have become apparent. A case of an adult patient with
      infantile nephropathic cystinosis is reported. He presented with many long-term
      ocular complications of cystinosis. After 4 years of follow-up, the patient died
      from sepsis. Pathology of the phthisical eyes demonstrated numerous electron
      transparent polygonal spaces, bounded by single membrane, in corneal cells,
      retinal pigment epithelial cells, and even choroidal endothelial cells. The
      ophthalmic manifestations and pathology of infantile nephropathic cystinosis are
      discussed and reviewed in light of the current report and other cases in the
      literature.

PMID- 17212994
TI  - Charles Bonnet, his life, and his syndrome.
AB  - Charles Bonnet (1720-1792) was an eminent naturalist and philosopher whose
      contributions to botany and philosophy were highly regarded and honored by his
      contemporaries in the scientific community of his era in France and England.
      In1760 he first described and analyzed formed visual hallucinations experienced
      by his grandfather. The syndrome was named after Bonnet in 1937 by George de
      Mosier, another native of Geneva, Switzerland.

PMID- 17212995
TI  - Prognostic factors for visual outcome in purtscher retinopathy.

PMID- 17212997
TI  - Expanding options with a wider range of rosuvastatin doses.
AB  - BACKGROUND: The dose range for rosuvastatin in Europe has recently been expanded
      to 5 to 40 mg and is now in line with the dose range currently available in the
      United States. OBJECTIVE: The goal of this article was to review the efficacy and
      safety data available for the rosuvastatin 5-mg dose and discuss these data in
      the context of the full 5- to 40-mg dose range. METHODS: Articles referring to
      clinical efficacy or safety data for the 5-mg dose of rosuvastatin were
      identified and reviewed after a search of the MEDLINE database (2000-August 2006;
      English language only) using the search term rosuvastatin. Proceedings from major
      cardiology congresses (2000-2006) were also searched for additional information.
      RESULTS: Rosuvastatin 5 mg is significantly (P < 0.001) more effective at
      reducing low-density lipoprotein cholesterol (LDL-C) and total cholesterol (42%
      and 30%) levels compared with atorvastatin 10 mg (36% and 27%), simvastatin 20 mg
      (36% and 25%), and pravastatin 20 mg (27% and 19%). Rosuvastatin 5 mg allows
      significantly more patients to reach their LDL-C goals as recommended by the 2003
      European guidelines and the Third Report of the National Cholesterol Education
      Program Expert Panel on Detection, Evaluation, and Treatment of High Blood
      Cholesterol in Adults (Adult Treatment Panel III) (49%-52% and 67%-71%) than
      atorvastatin 10 mg (36%, P < 0.001; 53%, P < 0.01), simvastatin 20 mg (37%, P <
      0.001; 64%, P < 0.05), and pravastatin 20 mg (12%, P < 0.001; 49%, P < 0.001).
      Rosuvastatin is well tolerated across the 5- to 40-mg dose range, with a type and
      incidence of adverse events similar to the other commonly available, but less
      effective, statins. The introduction of a 5-mg dose offers greater flexibility to
      prescribing physicians in that it provides an additional dosing option for those
      patients who are at a lower cardiovascular risk or who have an increased
      potential for developing myopathy with statin therapy. CONCLUSIONS: Rosuvastatin
      5 mg is well tolerated and has beneficial effects across the atherogenic lipid
      profile by reducing LDL-C and total cholesterol, raising high-density lipoprotein
      cholesterol, and helping a greater proportion of patients reach their LDL-C
      goals.

PMID- 17212998
TI  - Role of abatacept in the management of rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) has been associated with significant
      morbidity and economic burden. Traditional pharmacotherapy (eg, NSAIDs,
      corticosteroids, disease-modifying antirheumatic drugs [DMARDs]) can be
      inadequate in controlling symptoms and disease progression. Abatacept is the
      first selective co-stimulation modulator approved by the US Food and Drug
      Administration for the management of RA. It is a fusion protein developed to
      modulate the T-cell co-stimulatory signal that is mediated through the CD28
      CD80/86 pathway. OBJECTIVE: The objective of this manuscript was to review the
      clinical pharmacology, pharmacokinetic and pharmacodynamic properties,
      tolerability, and clinical efficacy of abatacept. METHODS: MEDLINE and
      International Pharmaceutical Abstracts were searched through June and May,
      respectively, of 2006 using the term abatacept or CTLA4-Ig. All prospective,
      randomized, Phase II and III trials, and their extension phases, were included.
      RESULTS: Phase II and III clinical trials found that abatacept, at a dose of 10
      mg/kg administered as a short i.v. infusion in combination with DMARDs, was
      associated with significant clinical benefit in patients with active RA. After 6
      months of treatment, the American College of Rheumatology (ACR) criteria for 20%
      clinical improvement (ACR20 response) was attained in 41.9% to 67.9% of patients
      who received abatacept compared with 19.5% to 39.7% of patients who received
      placebo (P < 0.001). The percentages of patients achieving the ACR criteria for
      50% and 70% clinical improvement (ACR50 and ACR70) were 20.3% to 39.9% and 10.2%
      to 19.8%, respectively, in the groups that received abatacept compared with 3.8%
      to 16.8% and 1.5% to 6.5%, respectively, in the patients who received placebo (P
      = 0.03 and P < 0.001). Additionally, abatacept was found to improve disease
      activity, physical function, pain, and health-related quality of life (HRQOL).
      The most commonly reported adverse effects associated with abatacept treatment
      were headache (18.2%), upper respiratory tract infection (12.7%), nasopharyngitis
      (11.5%), and nausea (11.5%). The incidences of infections and serious infections
      were higher in the group that received abatacept compared with patients who
      received placebo (53.8% vs 48.3% and 3.0% vs 1.9%, respectively; P not reported).
      No significant between-group differences in mortality were found. CONCLUSIONS:
      Available evidence suggests that abatacept was effective in controlling symptoms
      and improving HRQOL in patients with active RA and an inadequate response to
      DMARD therapy. The most commonly reported adverse effects associated with
      abatacept treatment were headache, upper respiratory infection, nausea, and
      nasopharyngitis. Additional trials are needed to determine the long-term safety
      profile of this agent and whether the clinical benefits of abatacept found in the
      current clinical trials will be sustained over time.

PMID- 17212999
TI  - Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies.
AB  - BACKGROUND: Bevacizumab is a recombinant humanized monoclonal antibody that was
      approved by the US Food and Drug Administration (FDA) in February 2004 for use as
      part of combination therapy with fluorouracil-based regimens for metastatic
      colorectal cancer (mCRC). OBJECTIVES: This article reviews the mechanism of
      action, clinical pharmacology, and pharmacodynamic and pharmacokinetic properties
      of bevacizumab. It summarizes data on the clinical efficacy and tolerability of
      bevacizumab from Phase II/III trials in mCRC, breast cancer, non-small-cell lung
      cancer, and renal cell carcinoma and preliminary data from investigational
      studies in pancreatic cancer and soft-tissue sarcomas. The dosing and
      administration of bevacizumab also are discussed. METHODS: A comprehensive search
      of the English-language literature indexed on MEDLINE (1966-April 2006) was
      performed using the terms Avastin, bevacizumab, vascular endothelial growth
      factor, angiogenesis, and bevacizumab plus colorectal cancer, breast cancer, non
      small-cell lung cancer, pancreatic cancer, and renal cell carcinoma. Published
      abstracts from American Society of Clinical Oncology annual meetings from 2002 to
      2006, FDA submission documents, and the product information for bevacizumab also
      were reviewed. Pertinent review articles, preclinical studies, and editorials and
      all published Phase II/III clinical trials were selected for review. The
      reference lists of identified articles were examined for additional publications.
      RESULTS: Bevacizumab exhibits linear pharmacokinetics in the dose range between
      0.3 and 10 mg/kg q2-3wk and steady state, which is reached in approximately 100
      days. The estimated t(1/2) of bevacizumab is approximately 20 days. After
      correction for body weight, clearance and V(d) are reported to be a respective
      26% and 22% higher in men than in women. Statistical analyses have not been
      performed, however, and the clinical impact of these gender differences has not
      been assessed. No dose adjustment is currently recommended based on age, sex, or
      renal function. Bevacizumab has been reported to result in changes in exposure to
      concomitant chemotherapy, although formal drug-interaction studies have not been
      performed. Surrogate markers of disease progression or treatment response to
      bevacizumab have been studied, but no significant correlations with any outcome
      measure have been found. When combined with standard chemotherapy regimens,
      bevacizumab has been associated with significant improvements compared with
      chemotherapy alone in the efficacy end points of overall survival, progression
      free survival, and response rates in patients with mCRC (all, P < 0.05). Based on
      these findings, bevacizumab is considered a first-line option for this disease.
      Combination bevacizumab regimens have been associated with clinical activity in
      breast cancer, non-small-cell lung cancer, renal cell carcinoma, pancreatic
      cancer, and soft-tissue sarcoma. The observed toxicities of bevacizumab include
      hypertension, proteinuria, mild to moderate hemorrhage, wound healing
      complications, and thromboembolic events. A bevacizumab dose of 5 mg/kg q2wk has
      been established as effective and well tolerated in the setting of mCRC. A
      variety of dosing schemes have been investigated in other solid neoplasms, but no
      consensus has been reached on the optimal bevacizumab regimen. CONCLUSIONS:
      Bevacizumab is effective and generally well tolerated as first-line therapy for
      mCRC. The results from clinical studies of bevacizumab as a single agent or as
      part of combination regimens for breast cancer, non-small-cell lung cancer, renal
      cell carcinoma, and other solid malignancies have been promising. The most
      effective regimens for various malignancies and predictive markers of treatment
      response have not been fully determined. Combining bevacizumab with chemotherapy
      or other novel targeted agents appears to be a rational approach that may enhance
      efficacy while limiting the traditional nonselective toxicities.

PMID- 17213000
TI  - Patients' and physicians' perceptions of the travoprost dosing aid: an open
      label, multicenter study of adherence with prostaglandin analogue therapy for
      open-angle glaucoma or ocular hypertension.
AB  - OBJECTIVE: This study describes patients' and physicians' perceptions of issues
      related to dosing adherence with topical therapies for lowering intraocular
      pressure before and after use of the travoprost dosing aid (Travatan Dosing Aid,
      Alcon Research Ltd., Fort Worth, Texas). METHODS: The study had an open-label,
      multicenter, single-treatment-arm design that included sequential patients with
      open-angle glaucoma (with or without pigment dispersion or pseudoexfoliation
      component) or ocular hypertension who were taking any prostaglandin analogue
      monotherapy. Ten participating physicians were chosen on the basis of factors
      such as their experience, qualifications, and previous clinical study
      participation. The study consisted of 2 visits: screening and week 4. Patients
      were asked to complete a survey about their medication adherence before study
      entry at the screening visit and at study exit during the week-4 visit. In
      addition, each physician was asked to complete an entry and exit survey on each
      patient as well as a survey to provide feedback on the travoprost dosing aid.
      RESULTS: Of the 87 enrolled patients, 6 did not complete the exit survey;
      therefore, 81 patients were included in the intent-to-treat analysis. Mean (SD)
      age at enrollment was 65.4 (11.6) years; 61.7% (50/81) of the patients were women
      and 60.5% (49/81) were white. Most patients (96.3% [78/81]) had open-angle
      glaucoma. Participating physicians perceived that problems involving dosing and
      adherence were reduced after patients used the dosing aid. Physicians indicated
      that they would recommend continued use of the travoprost dosing aid for 91.3%
      (73/80) of patients. All 10 participating physicians said that they would
      recommend the dosing aid to patients in the future. Of the 81 patients, the
      majority (68.8% [55/80]) indicated that they would like to continue using the
      travoprost dosing aid. For 67.5% (54/80) of patients, dosing adherence as
      recorded by the travoprost dosing aid was >70%. The dosing lever (39.7% [31/78])
      and the visual alarm (29.5% [23/78]) were the 2 most favored features of the
      dosing aid reported by all evaluable patients. The majority of patients (58.8%
      [47/80]) indicated that they were "relieved" or "very relieved" that the doctor
      was able to monitor when they dosed their medication; few (7.5% [6/80]) were
      "concerned" or "very concerned" that the doctor was able to monitor their dosing.
      CONCLUSIONS: The travoprost dosing aid was perceived to be effective in reminding
      this group of patients to take their medication as prescribed. In this study, the
      device was well accepted by both patients and physicians.

PMID- 17213001
TI  - Effects of receipt of chronic statin therapy before the onset of acute myocardial
      infarction: a retrospective study in patients undergoing primary percutaneous
      coronary intervention.
AB  - BACKGROUND: Studies have reported an association between receipt of statin
      therapy and a reduction in complications after elective percutaneous coronary
      intervention (PCI). However, there are limited data on the effects of chronic
      statin therapy before the occurrence of an acute myocardial infarction (AMI).
      OBJECTIVE: This study investigated whether administration of chronic statin
      therapy before AMI was associated with a reduction in reperfusion injury in AMI
      patients undergoing PCI. METHODS: This was a retrospective study of consecutive
      patients with a first AMI who underwent successful reperfusion therapy with PCI
      within 24 hours after the onset of AMI between April 1998 and October 2003.
      Patients were stratified according to whether they had or had not been receiving
      chronic statin therapy for > or = 1 month before the onset of AMI. The following
      end points were compared after PCI: electrocardiographic resolution of ST segment
      elevation, defined as a reduction of > or = 50% from the initial value;
      achievement of Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow;
      corrected TIMI frame count (cTFC); maximum serum creatine kinase (CK) level; and
      the type and frequency of ventricular arrhythmias. RESULTS: The study enrolled
      386 patients, 40 of whom had been receiving statin therapy before the onset of
      AMI. The clinical characteristics of the 2 groups were similar at baseline, with
      the exceptions of a significantly higher rate of hyperlipidemia in the statin
      group compared with the nonstatin group (P < 0.001), significantly greater
      chronic use of aspirin therapy (P < 0.001), and significantly greater chronic use
      of antihypertensive medications (beta-blockers: P = 0.004; angiotensin-converting
      enzyme inhibitors/angiotensin II-receptor blockers: P = 0.007; calcium channel
      blockers: P = 0.006). Electrocardiographic ST segment resolution after PCI was
      observed in 87.5% and 69.9% of the statin and nonstatin groups, respectively
      (hazard ratio [HR]: 3.01; 95% CI, 1.15-7.90; P = 0.025). Achievement of TIMI
      grade 3 flow after PCI was seen in 95.0% of the statin group and 83.5% of the
      nonstatin group (HR: 3.75; 95% CI, 0.88-16.0; P = NS). Patients treated with a
      statin had a significantly lower mean (SD) maximum CK level compared with the
      nonstatin group (2300 [1449] vs 3538 [3170] IU/mL, respectively; P = 0.015) and a
      lower cTFC after PCI (18.8 [4.0] vs 24.2 [14.2]; P = 0.017). The difference in
      reperfusion arrhythmias between groups was not statistically significant. After
      adjustment for baseline covariates, pretreatment with a statin was found to be an
      independent predictor of ST segment resolution after PCI (HR: 2.95; 95% CI, 1.08
      8.09; P = 0.035) and prevention of impaired coronary flow (HR: 3.00; 95% CI, 1.63
      5.55; P < 0.001). CONCLUSION: In this study, receipt of chronic statin therapy
      before the onset of AMI was associated with improvement in epicardial perfusion
      and a reduction in myocardial necrosis after PCI.

PMID- 17213002
TI  - Effects of ibuprofen on sleep quality as measured using polysomnography and
      subjective measures in healthy adults.
AB  - BACKGROUND: Although some literature has suggested that NSAIDs may affect sleep
      physiology, this observation is not consistent with clinical use of these drugs
      and has not been verified using standard sleep-research methodologies. OBJECTIVE:
      This study was undertaken to determine whether ibuprofen 400 mg administered at
      3, 7, and 11 pm (total daily dose, 1200 mg) produced any significant alterations
      in the character and quality of night-time sleep as measured by standard sleep
      laboratory polysomnography (PSG) and subjective measures. METHODS: This 4-day,
      multiple-dose, double-blind, randomized, placebo-controlled trial was conducted
      in a hospital-based, sleep laboratory in the United States (DENT Neurological
      Institute at Millard Fillmore Hospital, Buffalo, New York). Healthy subjects aged
      > or = 18 years spent 3 consecutive nights in a sleep laboratory. Day 1/night 1
      was for acclimation; day 2/night 2, for baseline PSG and subjective sleep
      assessments; and day 3/night 3, for treatment effects on sleep character and
      quality. All subjects received placebo on days 1 and 2. On day 3, subjects
      received ibuprofen 400 mg or placebo TID. RESULTS: All 30 subjects (15 per group)
      completed the study (18 men, 12 women; all white). The mean age (SD) was 28.6
      years and mean body weight was 71.4 kg. In both groups, mean values for sleep
      efficiency and quality of sleep were significantly higher on night 3 compared
      with baseline; the mean (SD) changes from baseline were not significantly
      different between the ibuprofen and control groups (sleep efficiency, 0.4 [6.3]
      and 0.3 [6.2]; quality of sleep, 8.6 [26.8] and 3.3 [21.3]). Mean night-3 sleep
      efficiency in the ibuprofen group was 88.6%--substantially higher than the
      minimally acceptable sleep efficiency of 75% stated in the protocol. Three mild
      adverse events were reported in 2 subjects. CONCLUSION: This study found that in
      these subjects a total daily dose of 1200 mg ibuprofen did not produce any
      clinically or statistically significant alterations in the character and quality
      of nighttime sleep as measured using standard sleep laboratory PSF and subjective
      measures.

PMID- 17213003
TI  - Cardiovascular events associated with the use of four nonselective NSAIDs
      (etodolac, nabumetone, ibuprofen, or naproxen) versus a cyclooxygenase-2
      inhibitor (celecoxib): a population-based analysis in Taiwanese adults.
AB  - BACKGROUND: Serious cardiovascular events (CVEs) have been linked to the use of
      cyclooxygenase (COX)-2 inhibitors, a category of selective NSAIDs. However, few
      studies are available that have compared the risk for CVEs between COX-2
      inhibitors and nonselective NSAIDs in adults undergoing long-term treatment.
      OBJECTIVES: The present study assessed (1) whether long-term use of nonselective
      NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) is associated with an
      increased risk for treatment-related CVEs (acute myocardial infarction [AMI],
      angina, cerebrovascular attack [CVA], and/or transient ischemic attack [TIA])
      compared with long-term use of celecoxib and (2) which factors are associated
      with the risk for treatment-related CVEs in long-term users of nonselective
      NSAIDs in Taiwan. METHODS: This population-based analysis used data from the
      Taiwanese Bureau of National Health Insurance (Taipei, Taiwan) database. Eligible
      patients were aged > or = 18 years and had been receiving etodolac, nabumetone,
      ibuprofen, naproxen, or celecoxib for > or = 180 days between January 1, 2001,
      and December 31, 2003. The primary outcomes measure was the prevalence of serious
      CVEs (AMI, angina, CVA, and/or TIA requiring hospitalization) after initiation of
      treatment. Analyses were performed on data from all eligible patients; person
      time exposures to the drugs and hazard ratios (HRs) were calculated to determine
      the risk for CVEs with long-term use. RESULTS: A total of 16,326 patients (8166
      men, 8160 women; mean [SD] age, 61.83 [20.23] years) who had received long-term
      treatment with etodolac (2014 [12.34%]), nabumetone (2262 [13.86%]), ibuprofen
      (5239 [32.09%]), naproxen (3049 [18.68%]), or celecoxib (3762 [23.04%]) were
      identified. The overall prevalences of AMI, angina, CVA, and TIA were higher in
      long-term users with a history of cardiovascular disease (CVD) than in those
      without (AMI, 4.76% vs 0.99%; angina, 4.11% vs 0.43%; CVA, 7.74% vs 1.51%; and
      TIA, 4.03% vs 0.52%) (all, P < 0.01). The HRs for AMI, angina, CVA, and TIA were
      not significantly different between the NSAID and celecoxib groups. History of
      CVD played a significant role in recurrence during the period studied; the HRs
      (95% CIs) were 2.29 (1.22-4.32) for AMI, 6.19 (3.56-10.78) for angina, 3.56 (2.80
      4.52) for CVA, and 6.60 (3.72-11.73) for TIA. Preexisting medical conditions
      (hypertension, dyslipidemia, diabetes mellitus, congestive heart failure, chronic
      renal disease) also significantly affected the risk for CVEs. CONCLUSIONS: In
      this cohort study of long-term (> or = 180 days) use of NSAIDs in Taiwanese
      adults, no significant differences in the risk for treatment-related CVEs were
      observed between groups prescribed 1 of 4 nonselective NSAIDs (etodolac,
      nabumetone, ibuprofen, or naproxen) or celecoxib. History of CVD was the most
      significant determinant of CVE risk. Patients with preexisting medical conditions
      appeared to have a significantly higher risk for CVEs associated with the use of
      NSAIDs and celecoxib compared with patients without these conditions.

PMID- 17213004
TI  - Pharmacokinetic and pharmacodynamic characteristics of a new S-amlodipine
      formulation in healthy Korean male subjects: a randomized, open-label, two
      period, comparative, crossover study.
AB  - BACKGROUND: Amlodipine, a dihydropyridine calcium channel antagonist, is
      prescribed for the management of angina and hypertension. It is used
      therapeutically as a racemic mixture, composed of S- and R-enantiomers, but its
      calcium channel-blocking effect is confined to S-amlodipine; R-amlodipine has
      1000-fold less activity than its S-enantiomer. OBJECTIVE: The objective of this
      study was to compare the pharmacokinetic and pharmacodynamic properties and
      safety profiles of a newly developed amlodipine formulation, composed wholly of S
      amlodipine, with those of the conventionally prescribed racemic formulation.
      METHODS: This randomized, open-label, 2-period, comparative, crossover study was
      conducted with healthy volunteers at the Gil Medical Center and Gachon Medical
      School, Incheon, Korea. Male subjects, aged 20 to 50 years, were eligible to
      participate if their weight was within 20% of ideal body weight and if they were
      judged by physicians to be healthy. All subjects were randomly assigned in a 1:1
      ratio to 1 of 2 treatment sequences: (1) a single dose of the test amlodipine
      formulation (S-enantiomer amlodipine 5 mg p.o.) (Lodien [Hanlim Pharmaceutical
      Co., Seoul, Korea]) in the first study period, followed by a single dose of the
      reference amlodipine formulation (racemate 10 mg p.o.) (Norvasc [Pfizer
      Pharmaceuticals Korea Ltd., Seoul, Korea]) in the second study period, or (2) a
      single dose of the reference formulation in the first study period, followed by a
      single dose of the test formulation in the second period. A 3-week washout
      occurred between study periods. Blood samples for pharmacokinetic analysis of S
      amlodipine were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96,
      120, 144, and 168 hours after drug administration. Pharmacodynamic variables (ie,
      systolic and diastolic blood pressure and heart rate) were measured at 1, 2, 3,
      4, 5, 6, 7, 8, 9, 10, 12, 24, 48, and 72 hours after administration. Safety
      profiles were also assessed. Hematology, biochemistry, electrocardiography, and
      urinalysis were performed at baseline and end of study. Adverse events were
      monitored throughout the study period. Pharmacokinetic characteristics were
      compared using noncompartmental analysis. Pharmacokinetic equivalence was
      concluded if the geometric mean ratios of the plasma Cmax and AUC were within the
      predetermined range of 80% to 125%. RESULTS: Twenty-six healthy Korean male
      volunteers were screened and 18 subjects (mean [SD] age, 23.4 [1.5] years [range,
      21-26 years]; mean [SD] weight, 69.3 [6.8] kg [range, 60-88 kg]) were enrolled
      and completed the study. The plasma concentration-time profiles of S-amlodipine
      were comparable after administration of both formulations. The mean (SD) values
      for Cmax AUC from time 0 to the last available measurement (AUC(last)), and AUC
      from 0 to infinity (AUC(0-infinity)) for the reference formulation (3.0 [0.6]
      ng/mL, 151.4 [35.7] ng x h/mL, and 175.3 [45.1] ng x h/mL, respectively) did not
      differ significantly from those for the test formulation (3.1 [0.6] ng/mL, 139.7
      [40.3] ng x h/mL, and 161.7 [43.8] ng x h/mL, respectively). The calculated 90%
      Cls for the corresponding ratios of log-transformed Cmax, AUCO(0-infinity), and
      AUC(last) were 97.56% to 112.51%, 86.31% to 98.74%, and 83.46% to 100.04%,
      respectively, which met the predetermined criteria for pharmacokinetic
      equivalence. Despite the single administration, significant changes in maximal
      blood pressure and heart rate were observed after drug administration for both
      formulations, compared with baseline values (all, P < 0.001). However, no
      significant differences were observed between the 2 formulations in terms of
      pharmacodynamic profiles, and no clinically relevant changes were observed for
      either formulation with respect to physical examination, hematology,
      biochemistry, electrocardiography, or urinalysis. Neither formulation caused any
      serious adverse events. CONCLUSIONS: Two amlodipine formulations were found to be
      equivalent in terms of the pharmacokinetics of S-amlodipine. The newly developed
      formulation, comprised of only S-amlodipine, had pharmacodynamic profiles
      comparable to those of the conventional racemic amlodipine formulation in these
      healthy Korean male subjects. Both formulations were well tolerated.

PMID- 17213005
TI  - Self-reported compliance with topical cyclosporine emulsion 0.05% and onset of
      the effects of increased tear production as assessed through patient surveys.
AB  - BACKGROUND: Keratoconjunctivitis sicca is a common eye condition characterized by
      itchiness, redness, and dryness due to a lack of tear production or abnormalities
      in the tear film. Cyclosporine works to increase the production of natural tears,
      which contain nutrients and proteins not found in artificial tears. OBJECTIVE:
      The purpose of this report was to assess the association between self-reported
      compliance with topical cyclosporine 0.05% emulsion and the onset of effects of
      increased tear production in patients with dry eye. METHODS: Practicing
      physicians were asked to identify patients for whom treatment with cyclosporine
      was appropriate and who were willing to participate in the study. Patients who
      agreed to participate were given medication samples and study materials. The
      participants were asked to respond to automated survey questions before they used
      cyclosporine and 30 and 60 days after initiating cyclosporine. Participants were
      asked how frequently they used the medication, how rapidly their symptoms were
      relieved, and whether they intended to continue using cyclosporine. RESULTS: Of
      the 5367 patients initially enrolled in the study, 3145 (59%) patients completed
      the baseline and 60-day follow-up surveys. The mean age of the participants was
      60 years; 2677 (85%) of them were women, and 468 (15%) were men. Compliance with
      cyclosporine therapy was reported as follows: 2477 (79%) participants said they
      used cyclosporine twice daily as prescribed by their physicians, 468 (15%)
      reported missing some doses of cyclosporine, and 189 (6%) reported missing -50%
      or > or = 50% of the doses. The effects of increased tear production were
      reported to occur significantly sooner in participants who complied with
      cyclosporine treatment as prescribed than in those who did not comply with
      treatment (P < 0.01). Among those who complied with treatment, 1822 (73%)
      participants reported experiencing the effects of increased tear production in <
      5 weeks compared with 468 (70%) participants who did not comply with treatment.
      Overall, the mean rate of satisfaction with cyclosporine was 7.5 on a scale from
      0 (not at all satisfied) to 10 (very satisfied). Participants who reported using
      cyclosporine twice daily as prescribed gave satisfaction with cyclosporine a mean
      rating of 7.7 compared with 7.3 given by those who missed some doses and 5.3 from
      those who missed approximately 50% or > or = 50% of the doses (P < 0.01). An
      intention to continue using cyclosporine was reported by 2611 (83%) participants.
      CONCLUSION: The results of this study in participants using cyclosporine for dry
      eye in an actual-practice setting suggest an association between patient-reported
      compliance with medication and more rapid onset of the effects of increased tear
      production.

PMID- 17213006
TI  - Gatifloxacin-induced hyperglycemia: a case report and summary of the current
      literature.
AB  - BACKGROUND: Gatifloxacin is a fluoroquinolone antibiotic that has been associated
      with severe hypoglycemic and hyperglycemic events. OBJECTIVE: The purpose of this
      report was to describe a new case of gatifloxacin-associated hyperglycemia in an
      elderly patient and to provide a summary of case reports. CASE SUMMARY: A male
      patient, aged 86 years, was hospitalized with small bowel obstruction due to
      adhesions from a previous appendectomy. At the time of admission, the patient
      weighed 78.5 kg (ideal body weight, 73 kg), had a body mass index of 24.8 kg/m2,
      and had a calculated creatinine clearance of 45.6 mL/min. The patient's hospital
      medications were metoprolol, diltiazem, subcutaneous heparin, ranitidine,
      vancomycin, piperacillin/tazobactam, and aspirin. He also was treated with
      gatifloxacin 400 mg QD for suspected pneumonia during the hospital stay. After 4
      days of the gatifloxacin regimen, the patient's mean blood glucose concentration
      increased from 133 mg/dL at the time of admission to 537 mg/dL. Although the
      patient exhibited signs of glycosuria (ie, urine glucose concentration >1000
      mg/dL), he did not complain of symptoms of hyperglycemia, such as polyuria,
      polyphagia, or polydipsia. The hyperglycemia resolved after administration of
      gatifloxacin was discontinued and the patient had received regular insulin 15 U
      SC over 5 hours. DISCUSSION: The exact mechanism by which gatifloxacin induces
      hyperglycemia is unknown, but it may be related to vacuolation of pancreatic beta
      cells, leading to a decrease in insulin secretion. This case, along with the 15
      other summarized cases, adds to the evidence for an association between
      gatifloxacin and hyperglycemia. These patients had other risk factors that may
      have contributed to the development of hyperglycemia, including age >65 years and
      renal impairment. CONCLUSION: An elderly patient with no history of diabetes
      developed severe hyperglycemia after receiving doses of gatifloxacin 400 mg that
      had not been adjusted for age-related renal impairment. The hyperglycemia
      resolved after discontinuation of gatifloxacin.

PMID- 17213007
TI  - Pharmacokinetic properties of esomeprazole in children aged 1 to 11 years with
      symptoms of gastroesophageal reflux disease: a randomized, open-label study.
AB  - OBJECTIVE: The aim of this study was to assess the overall exposure, other
      pharmacokinetic (PK) properties, and tolerability of esomeprazole magnesium after
      repeated oral doses of 5, 10, and 20 mg in pediatric patients who had symptoms of
      gastroesophageal reflux disease (GERD). METHODS: This randomized, open-label
      study was conducted at West Coast Clinical Trials, Long Beach, California. Boys
      and girls aged 1 to 11 years who had a clinical diagnosis of GERD were included
      and stratified by age (1-5 years [younger group] and 6-11 years [older group]).
      For this 5-day study, children in the younger group were randomly assigned to
      receive 1 esomeprazole 5- or 10-mg capsule p.o. QD, and those in the older group
      were randomly assigned to receive 1 esomeprazole 10- or 20-mg capsule p.o. QD. On
      days 1 to 4, study medications were administered with the supervision of the
      study personnel 1 hour before breakfast. Blood samples were collected within 0.5
      hour before and 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hours after study drug
      administration on day 5. Plasma concentrations of esomeprazole were measured
      using reverse-phase liquid chromatography and mass-spectrometric detection.
      Tolerability assessments were performed by reviewing the number and severity of
      adverse events (collected via spontaneous reporting and direct questioning) and
      findings from the physical examination, which included vital-sign measurements
      and laboratory analysis (hematology, biochemistry, and urinalysis). Site
      personnel supervised the administration of the study drug to ensure compliance
      with treatment. RESULTS: The study included 31 children (17 boys, 14 girls; mean
      age, 5 years; 18 children in the younger group, 13 in the older group). A total
      of 27 children were included in the PK analysis. In the younger group, the
      geometric mean AUC(0-infinity) and Cmax values in the esomeprazole 10-mg group
      were >2-fold that in the 5-mg group (AUC(0-infinity), 4.83 and 0.74 pmol x h/L
      [0.32 and 0.04 micromol x h x L(-1)/kg], respectively; Cmax, 2.98 and 0.62
      micromol/L [0.19 and 0.03 micromol/L x kg(-1)], respectively). In the older
      group, the geometric mean AUC(0-infinity) and Cmax values for the 20-mg dose
      group were approximately 2-fold those for the 10-mg dose group (AUC(0-infinity),
      6.28 and 3.70 micromol x h/L [0.21 and 0.12 pmol x h x L(-1)/kg], respectively;
      Cmax, 3.73 and 1.77 micromol/L [0.13 and 0.06 micromol/L x kg 1], respectively).
      For the 10-mg esomeprazole dose, the geometric mean body-weight-normalized
      apparent oral clearance was approximately 50% higher in the younger group
      compared with the older group (0.40 and 0.25 L/h x kg(-1), respectively). Thirty
      patients were included in the tolerability analysis. The adverse events that
      occurred were skin excoriation, discolored feces, and skin laceration (1 [3.3%]
      patient each); none were considered related to treatment. CONCLUSIONS: The
      results of this small study suggest that, in children aged 1 to 11 years who had
      GERD, the PK properties of esomeprazole may be both dose and age dependent and
      that younger children might have a more rapid metabolism of esomeprazole per
      kilogram of body weight compared with older children. Esomeprazole was well
      tolerated at doses of 5, 10, and 20 mg in the pediatric patients studied.

PMID- 17213009
TI  - Measurable outcomes in psychiatric disorders: remission as a marker of wellness.
AB  - BACKGROUND: Mental disorders are highly prevalent, heterogeneous, and of
      multifactorial etiology. Collectively, they are associated with significant
      morbidity, mortality, and economic cost. Wellness is the optimal outcome in the
      management of chronic medical and psychiatric disorders. OBJECTIVES: This review
      provides a synopsis of definitions and operational criteria for remission in
      major depressive disorder, bipolar disorder, schizophrenia, anxiety disorders,
      and attention-deficit/hyperactivity disorder (ADHD). The overall goals were to
      propose a treatment framework that gives primacy to therapeutic outcomes and to
      provide a rationale for psychiatry to quantify and measure patient outcome.
      METHODS: Articles proposing definitions for remission were identified using a
      MEDLINE search (1966-April 2005) of the English-language literature (key terms:
      remission, anxiety disorders, bipolar disorder, major depressive disorder,
      attention-deficit/hyperactivity disorder, and schizophrenia). RESULTS:
      Operationalizing and quantifying critical end points in psychiatric disorders may
      help sharpen the focus of therapeutic activity and benefit patient outcome. In
      the absence of a validated biomarker of psychiatric illness activity, symptomatic
      remission and functional restoration are the only available markers of wellness
      in psychiatry. There is an emerging consensus regarding a definition for
      remission in major depressive disorder; several working definitions for bipolar
      disorder, schizophrenia, and anxiety disorders have been proposed. Developments
      in adult mood disorders-albeit incomplete-have been informative; managing
      psychiatric disorders that first appear in childhood (eg, ADHD) may also benefit
      by objectifying patient outcome. CONCLUSIONS: Research is needed to determine the
      impact of applying a remission-focused model of illness management--emphasizing
      quantifiable, objective, and measurable end points--on overall patient outcomes.

PMID- 17213010
TI  - Remission versus response as the goal of therapy in ADHD: a new standard for the
      field?
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has a substantial
      negative impact; however, within long-term follow-up studies, a proportion of
      patients do very well, both symptomatically and functionally, suggesting that the
      lower the symptom burden, the greater the functional improvements. Studies in
      major depressive disorder have identified a relationship between symptomatic
      remission and restoration of normal functioning. OBJECTIVE: The purpose of this
      article was to propose a definition of remission in ADHD, review remission rates
      in clinical trials for commonly used medications, and explore the relationship
      between symptomatic remission and optimal functioning. METHODS: Remission and
      response rates for medications were obtained through MEDLINE searches of English
      language citations (1999-2005) and meeting abstracts (2003-2005) using the terms
      amphetamine, atomoxetine, methylphenidate, ADHD, efficacy, effectiveness, and
      controlled trial, as well as hand searches of efficacy studies. Evidence from
      randomized controlled trials, as well as effectiveness studies, where the
      proportions of patients achieving predefined cutoff points for remission or
      response are reported, was reviewed. Because higher remission rates were
      identified with the oral, osmotic, controlled-release system (OROS) of
      methylphenidate, a relationship between symptomatic response/remission and
      optimal functioning was explored further. RESULTS: Remission in ADHD should be
      defined as a loss of diagnostic status, minimal or no symptoms, and optimal
      functioning when individuals are being treated with or without medication.
      Symptomatic remission can be operationalized as a mean total score of S1 on most
      standardized questionnaires. For the medications examined (OROS methylphenidate,
      immediate-release methylphenidate, atomoxetine, and mixed amphetamine salts),
      response rates were comparable at approximately 70% to 75%; however, remission
      rates were higher with OROS methylphenidate compared with either immediate
      release methylphenidate or atomoxetine (remission rates with amphetamines were
      not found). Benefits, including decreased illness burden as well as improved
      psychosocial and academic functioning, were associated with treatment versus no
      treatment and were greater with medication that offered higher remission rates.
      CONCLUSIONS: The literature provided evidence that greater symptom improvements
      are associated with greater functional improvements, emphasizing that remission
      of ADHD as defined should be the goal of therapy. Treatment ought to include the
      early use of strategies with the greatest chance of achieving remission. Future
      clinical research should use remission as the primary outcome.

PMID- 17213011
TI  - The uninsured and underinsured in the United States: the saga continues.

PMID- 17213012
TI  - Compliance with refilling prescriptions for atypical antipsychotic agents and its
      association with the risks for hospitalization, suicide, and death in patients
      with schizophrenia in Quebec and Saskatchewan: a retrospective database study.
AB  - OBJECTIVE: The objective of this analysis was to describe the patterns of
      compliance with atypical antipsychotics among patients with schizophrenia in
      actual practice in 2 Canadian provinces and to examine the relation between
      degrees of compliance and the risks of hospitalization, suicide, and death.
      METHODS: Adults with a diagnosis of schizophrenia who filled at least 1
      prescription for risperidone, olanzapine, or quetiapine were identified in the
      Quebec public prescription drug insurance plan database (from July 1, 2001, to
      December 31, 2004) and the Saskatchewan Health database (from January 1, 1999, to
      December 31, 2003). Compliance was assessed based on the medication possession
      ratio, which was estimated as the proportion of days for which medication was
      available over each month of follow-up (> or = 80% = good compliance; 50%-79% =
      moderate compliance; < 50% = poor compliance). The association between the early
      and long-term effects of compliance and the risks of hospitalization, suicide,
      and death were examined using Cox regression, with adjustment for baseline age,
      sex, and use of antidepressants, sedatives, and lithium (Quebec only). RESULTS:
      respective 41,754 and 3291 patients were identified from the Quebec and
      Saskatchewan databases. Approximately half of the patients in each cohort were
      male and were aged < 45 years. Many patients had good compliance over the full
      follow-up period (Quebec, 61%; Saskatchewan, 45%); however, poor compliance was
      seen in 23% of patients from Quebec and 34% of those from Saskatchewan. Compared
      with poor compliance, the long-term effect of good compliance was associated with
      a significantly decreased risk of all-cause hospitalization (Quebec: adjusted
      hazard ratio [HR] = 0.60; 95% CI, 0.57-0.64; Saskatchewan: adjusted HR = 0.81;
      95% CI, 0.69-0.95) and psychosis-related hospitalization (Quebec: adjusted HR =
      0.37; 95% Cl, 0.34-0.40; Saskatchewan: adjusted HR = 0.45; 95% CI, 0.32-0.64).
      The Quebec data also indicated a significant association between good versus poor
      compliance and a decreased risk of death (adjusted HR = 0.58; 95% CI, 0.51-0.66)
      and suicide (adjusted HR = 0.68; 95% CI, 0.55-0.84) that was not observed in
      Saskatchewan. CONCLUSION: In this retrospective analysis of patients with
      schizophrenia in Quebec and Saskatchewan, good compliance with atypical
      antipsychotic medications was associated with substantial reductions in the risk
      for all-cause and psychosis-related hospitalizations.

PMID- 17213013
TI  - Cost-effectiveness of pregabalin for the management of neuropathic pain
      associated with diabetic peripheral neuropathy and postherpetic neuralgia: a
      Canadian perspective.
AB  - BACKGROUND: Neuropathic pain (NeP) is a chronic condition that occurs frequently
      with diabetes and herpes zoster infection. In addition to potentially lasting
      many years, the relationship between chronic pain, anxiety/depression, and sleep,
      also referred to as the triad of pain, causes functional impairment in many areas
      of life. OBJECTIVE: The aim of this study was to examine the 12-week cost
      effectiveness of 2 treatments of NeP, pregabalin versus gabapentin, in managing
      diabetic peripheral neuropathy (DPN) and postherpetic neuralgia (PHN) in a
      Canadian setting. METHODS: A stochastic simulation model evaluating NeP treatment
      was adapted to the Canadian setting. Using data from clinical trials of
      pregabalin (150-600 mg/d) and gabapentin (900-3600 mg/d), the model simulated 12
      week treatment outcomes for patients with DPN or PHN. Resource utilization was
      identified through an Internet-based survey among 80 Canadian physicians. Utility
      values (as measured using the EuroQol EQ-5D) were obtained from 126 NeP patients
      participating in a cross-sectional study conducted at Canadian primary care
      sites. The economic analysis was expressed as incremental cost per quality
      adjusted life year (QALY) gained and as incremental cost per day with no or mild
      pain. Model sensitivity to changes in key parameters was assessed. RESULTS:
      Following 12-week treatment, compared with gabapentin, pregabalin was projected
      to result in 6 and 9 additional days with no or mild pain for patients with DPN
      and PHN, respectively. Pregabalin therapy was estimated to provide an additional
      0.0047 QALY and 0.0086 QALY over gabapentin administration, for DPN and PHN,
      respectively. Mean (SE) direct costs per DPN patient were estimated as 837.53 Can
      dollars (37.31 dollars) (2004 dollars) with gabapentin and 818.49 dollars (36.50
      dollars) with pregabalin, and per PHN patient as 720.61 dollars (33.70 dollars)
      with gabapentin and 667.07 dollars (25.33 dollars) with pregabalin. Model
      findings were sensitive to variation in the dose and corresponding cost of the
      comparator, but not in other parameters. CONCLUSION: Based on the results of this
      analysis, in the treatment of NeP associated with DPN or PHN, pregabalin was a
      dominant or cost-effective treatment strategy compared with gabapentin.

PMID- 17213014
TI  - Symptom bother and health-related quality of life outcomes following solifenacin
      treatment for overactive bladder: the VESIcare Open-Label Trial (VOLT).
AB  - BACKGROUND: Most clinical trials designed to evaluate overactive bladder (OAB)
      syndrome treatments have focused on measuring micturition variables from bladder
      diaries. However, although diaries help physicians assess symptoms objectively,
      they lack information on patients' subjective experience of OAB symptoms and the
      effects of treatment. OBJECTIVE: The objective of this study was to assess
      patients' perceptions of improvements in symptom bother and health-related
      quality of life (HRQOL) with solifenacin succinate 5- and 10-mg treatments in
      patients with OAB. METHODS: VOLT (VESIcare Open-Label Trial) was a prospective,
      flexible-dosing trial performed at 207 centers in the United States. Ambulatory
      adult (aged > or = 18 years) men and women with an established diagnosis of OAB
      (urgency, urge urinary incontinence, frequency, and/or nocturia for > or = 3
      months) and who provided a sterile urine sample received solifenacin QD for 12
      weeks. Initially, all patients received 5 mg/d, with the option of adjustment to
      10 mg/d at 4 and 8 weeks. Effectiveness was assessed using the Patient Perception
      of Bladder Condition (PPBC) scale, a visual analog scale (VAS) for the degree of
      bother caused by individual OAB symptoms, and the overactive bladder
      questionnaire (OAB-q). Assessments were performed at study initiation and study
      end or study termination. Adverse events (AEs) were assessed throughout. RESULTS:
      Patients (N = 2225) were enrolled between June 2004 and April 2005. Patients with
      baseline data (n = 2205) had a mean (SD) age of 59.7 (14.4) years; most patients
      were women (1813 [82.2%]) and white (1761 [79.9%]). Of the total patients
      enrolled, 1743 (78.3%) completed all 12 weeks of the study. After 12 weeks of
      solifenacin treatment, improvement was observed in the mean values of patient
      reported perception of bladder condition. Significant change was observed on the
      PPBC scale from the mean baseline value to study end (4.4 vs 2.9; P < 0.001). All
      subscales of HRQOL significantly improved on the OAB-q score (mean changes, 14.7
      to 29.6; all, P < 0.001). On the VAS, there was a significant reduction in the
      degree of bother associated with urgency, urge urinary incontinence, frequency,
      and/or nocturia (mean changes in VAS ratings, -36.7 to -41.8; all, P < 0.001 vs
      baseline). Solifenacin was well tolerated in most patients. Treatment-emergent
      AEs were reported by 1321 (59.4%) patients. Most reported AEs were
      anticholinergic in nature and of mild to moderate severity: dry mouth, 477
      (21.4%); constipation, 295 (13.3%); headache, 76 (3.4%); blurred vision, 57
      (2.6%); nausea, 39 (1.8%); dyspepsia, 34 (1.5%); and dry eye, 29 (1.3%). Two
      hundred sixteen (9.7%) patients discontinued treatment due to AEs. CONCLUSION:
      Flexibly dosed solifenacin 5 and 10 mg QD was associated with reductions in
      patient-reported OAB symptom bother and improvements in patients' perception of
      bladder condition and HRQOL.

PMID- 17213016
TI  - Eradication of Helicobacter pylori with triple therapy: an epidemiologic analysis
      of trends in Turkey over 10 years.
AB  - BACKGROUND: There is increasing concern about the efficacy of current regimens
      for the eradication of Helicobacter pylori. OBJECTIVES: This study examined rates
      of H. pylori eradication with a commonly used triple-therapy regimen consisting
      of a proton pump inhibitor (PPI), clarithromycin, and amoxicillin in trials
      performed in Turkey from 1996 to 2005. It also investigated the relationship
      between eradication rates and the duration of treatment (7, 10, or 14 days),
      choice of PPI, and indication for treatment (dyspepsia or peptic ulcer). METHODS:
      This was a retrospective epidemiologic analysis. Articles concerning H. pylori
      eradication in Turkey that were published in peer-reviewed national and
      international journals were identified through searches of MEDLINE using the
      terms Helicobacter, eradication, and Turkey, and of the Turkish Medical Index
      using the terms Helicobacter and eradication. Abstracts from the Turkish
      Gastroenterology Congress from 1996 through 2005 were searched manually. Open
      label trials, controlled trials, treatment arms, and case series that included a
      triple-therapy regimen consisting of standard doses of any PPI (omeprazole 20 mg
      BID, lansoprazole 30 mg BID, pantoprazole 40 mg BID, or esomeprazole 40 mg BID)
      with clarithromycin 500 mg BID and amoxicillin 1 g BID for 7 to 14 days were
      selected for analysis. Trials including patients who had undergone a previous
      attempt at eradication of H. pylori were excluded. RESULTS: Of 138 trials or
      treatment arms identified, 94 met the criteria for inclusion (3637 subjects). The
      pooled eradication rate was 68.8% (95% CI, 67.3-70.3). A marked decrease in
      eradication was noted after 2000. Pooled eradication rates each year from 1996
      through 2005 were 79.4%, 83.7%, 81.8%, 81.8%, 75.1%, 61.3%, 65.6%, 65.1%, 55.3%,
      and 61.1%, respectively. Eradication rates were not affected by the duration of
      treatment, choice of PPI, or indication for treatment. CONCLUSIONS: Rates of H.
      pylori eradication with the triple-therapy regimen decreased in Turkey over the
      10-year period studied. In an era of increasing clarithromycin use, the
      effectiveness of this regimen for H. pylori eradication appears to require
      reassessment.

PMID- 17213015
TI  - Comparative cost-effectiveness of anticoagulation with bivalirudin or heparin
      with and without a glycoprotein IIb/IIIa-receptor inhibitor in patients
      undergoing percutaneous coronary intervention in Sweden: a decision-analytic
      model.
AB  - OBJECTIVE: This study modeled the comparative costs and effectiveness of
      anticoagulation with bivalirudin alone, heparin alone, and heparin combined with
      a glycoprotein IIb/IIIa-receptor inhibitor (GPI) in patients undergoing
      percutaneous coronary intervention (PCI) in Sweden. METHODS: GPIs are prescribed
      for -40% to 50% of patients undergoing PCI in Sweden. However, because treatment
      practices vary between hospitals, the model analyzed a cohort in which different
      proportions of patients (0%-100%) would receive a GPI in addition to heparin and
      the remaining patients would receive heparin monotherapy. This mixed cohort was
      compared with a cohort treated with bivalirudin. Abciximab was used as the GPI
      comparator, as this is the only GPI currently approved in Sweden for patients
      undergoing PCI. Pooled data from 3 studies (REPLACE-2 [second Randomized
      Evaluation of PCI Linking Angiomax to Reduced Clinical Events], ESPRIT
      [European/Australasian Stroke Prevention in Reversible Ischaemia Trial], and
      EPISTENT [Evaluation of Platelet IIb/IIIa Inhibitor for Stenting]) were used as
      the source for the probabilities of myocardial infarction (MI), urgent
      revascularization (UR), major and minor bleeding (Thrombolysis in Myocardial
      Infarction study definitions), and death. Treatment costs associated with these
      complications were obtained from 4 Swedish hospitals, and official drug prices
      were obtained from the Swedish Pharmacopoeia. All costs were presented in 2006
      Swedish kronor (SEK). The model was evaluated over a 30-day time frame from the
      perspective of a Swedish hospital. The modeled patient population was 63 years
      old, weighed 78 kg, and was 75% male. RESULTS: Compared with a pattern in which
      heparin plus a GPI was used in 50% of all PCIs and heparin alone was used in the
      remaining 50%, bivalirudin treatment was associated with a significant reduction
      in all complications in the model (P < 0.05), including a mean of 18.2 fewer MIs,
      1.6 fewer URs, 15.3 fewer bleeding events, and 1.3 fewer deaths per 1000 treated
      patients. Bivalirudin therapy also was associated with a significant reduction in
      total drug and health care costs per patient (SEK -1301; 95% Cl, -1367 to -1229).
      The benefit of bivalirudin was sensitive to the rate of GPI use: additional
      reductions in rates of MI, UR, and death were seen at lower rates of GPI use, and
      additional reductions in rates of bleeding and costs of drugs and health care
      utilization were seen at higher rates of GPI use. CONCLUSIONS: In this model,
      anticoagulation with bivalirudin in patients undergoing PCI was cost-effective
      compared with heparin alone and heparin plus a GPI. In a hypothetical Swedish
      hospital unit using equal proportions of heparin alone and heparin plus a GPI, a
      switch to bivalirudin would reduce the risk of both ischemic events and bleeding
      events, resulting in savings in total drug and health care costs.

PMID- 17213017
TI  - Cytogenetic characterization and gene expression profiling of the trastuzumab
      resistant breast cancer cell line JIMT-1.
AB  - Resistance to the HER-2 targeting drug trastuzumab can be observed clinically,
      but the lack of suitable experimental models hampers studies of resistance
      mechanisms. We characterized a HER-2-positive carcinoma cell line (JIMT-1)
      derived from a 62-year-old breast cancer patient which was clinically resistant
      to trastuzumab. Multicolor fluorescence in situ hybridization revealed a complex
      hyperdiploid karyotype with numerous marker chromosomes and unbalanced
      translocations. Comparative genomic hybridization (CGH) revealed numerous regions
      of copy number aberration (CNA). Further analysis by array CGH identified 27
      regions of CNA (16 amplified, 11 deleted). Thirty-eight percent of the genes in
      the amplified regions were overexpressed, compared to only 9% in regions of
      normal copy number ratios (CNR). Accordingly, 26% of the genes in the deleted
      regions were underexpressed, compared to 10% in regions of normal CNR. Most
      amplified and overexpressed genes were located on chromosome 1 as well as on 8q,
      12q14.1, 17q11 approximately q21, and 20q13. In 17q11 approximately q21, we
      identified two separate amplicons, the HER-2 amplicon and a previously unreported
      amplicon at 17q21.31. Several aberrant genes are implicated in cancer development
      (e.g., JUN, CDK4, and SLUG protooncogenes, as well as the drug/hormone
      metabolizing genes GSTM1 and CYP24). We conclude that cytogenetic and expression
      profiling of JIMT-1 revealed several new features that need further
      characterization and may shed light on trastuzumab resistance.

PMID- 17213018
TI  - A der(18)t(9;18)(p13;p11) and a der(9;18)(p10;q10) in polycythemia vera
      associated with a hyperproliferative phenotype in transformation to
      postpolycythemic myelofibrosis.
AB  - Chromosomal aberrations in polycythemia vera (PV) are heterogenous and nonrandom.
      A prognostic predictive value of these aberrations has not been established. The
      V617F mutation in the JAK2 gene on chromosome 9p24.1 was identified recently in
      peripheral blood leukocytes in the majority of patients with PV and in
      approximately half of patients with essential thrombocythemia and idiopathic
      myelofibrosis. Within the JAK2 V617F-positive PV patients, however, clinical
      presentation and degree of myeloproliferation varies to a great extent. Here we
      report four cases of chronic myeloproliferative disorders [two with PV, one with
      PV in transformation to idiopathic myelofibrosis (IMF) and one IMF patient], with
      the distinct karyotypic abberations der(18) t(9;18) (p13;p11) and
      der(9;18)(p10;q10). Two patients had hyperproliferative PV and two had
      "transitional PV" and IMF, respectively. All four patients harbored the JAK2
      V617F mutation. Our data, together with previously published data, clearly
      indicate an association of these chromosomal abnormalities with a highly
      proliferative PV phenotype with a propensity to transform into postpolycythemic
      myelofibrosis. Cytogenetic analysis seems to identify a subgroup of patients with
      a distinct prognostic profile, and should be performed in conjunction with a JAK2
      mutation analysis in patients suspected of a chronic myeloproliferative disease.

PMID- 17213019
TI  - Correlation of modified Shimada classification with MYCN and 1p36 status detected
      by fluorescence in situ hybridization in neuroblastoma.
AB  - Neuroblastoma (NB) is a childhood cancer derived from neural crest cells, with a
      highly variable clinical course and biologic behavior. NB cells harbor complex
      genetic changes. Also, MYCN amplification is a well-known molecular marker for
      aggressive progression, and deletion of the short arm of chromosome 1 is
      frequently observed in NB. The aim of this study was to investigate the
      correlation between genetic markers and prognostic morphological parameters to
      address the biology and underlying the clinical complexity of NB. Therefore, we
      performed fluorescence in situ hybridization analyses of chromosome band 1p36 and
      MYCN in a series of tumors from 43 cases classified according to the
      recommendation of International Neuroblastoma Pathology Committee (modification
      of Shimada classification). The correlations of MYCN amplification status and two
      distinct types of 1p36 alterations (deletion and imbalance) with Shimada
      classification and histologic prognostic factors were statistically analyzed.
      Amplification of MYCN and 1p36 deletion was present in 14 (32.6%) and 18 (41.9%)
      cases, respectively. Sixteen cases (37.2%) displayed a favorable histology, while
      27 (62.8%) had an unfavorable histology. The 1p36 deletion was found to be an
      independent predictor of unfavorable histology by multivariate analysis (logistic
      regression test, P = 0.03), but the 1p36 imbalance did not show any significance.
      Both 1p36 deletion and MYCN amplification showed significant correlation with
      undifferentiated tumors (chi-square test, P = 0.002 and 0.03, respectively).
      Highly significant correlation was found between the higher mitotic karyorrhectic
      index (MKI) and MYCN amplification (chi-square test, P < 0.001), whereas neither
      1p36 deletion nor 1p36 imbalance significantly correlated with a higher MKI (chi
      square test, P > 0.05). We conclude that 1p36 deletion may be a reliable
      parameter in determining unfavorable histology and predicting prognosis in NB.
      Further studies with prognostic data are needed to highlight its clinical
      significance.

PMID- 17213020
TI  - Bulky lymphadenopathy with poor clinical outcome is associated with ATM
      downregulation in B-cell chronic lymphocytic leukemia patients irrespective of
      11q23 deletion.
AB  - B-cell chronic lymphocytic leukemia (B-CLL) is the most common B-cell leukemia
      among older populations in Western countries. The clinical course of B-CLL is
      heterogeneous: in some patients the disease course is indolent, in others it is
      aggressive. The B-CLL subgroups with chromosome 11q23 deletion have been
      associated with aggressive disease course involving ATM deletion, extensive bulky
      lymphadenopathy (BLA), and inferior clinical outcome. Using real-time reverse
      transcriptase-polymerase chain reaction, we found that ATM was consistently
      underexpressed in B-CLL patients with BLA, irrespective of 11q23 deletion status.
      In addition, B-CLL patients who presented with BLA had a significantly shorter
      time to treatment (2 months) than did patients without BLA (74 months). Moreover,
      gene expression analysis in B-CLL patients with and without BLA revealed
      differences in expression for genes involved in apoptosis, cell cycle, and cell
      adhesion. These results indicate an association between BLA and reduced
      expression of ATM, suggesting a role for ATM in disease progression in B-CLL.

PMID- 17213021
TI  - High-resolution analysis of allelic imbalance in neuroblastoma cell lines by
      single nucleotide polymorphism arrays.
AB  - Genomic copy number changes are detectable in many malignancies, including
      neuroblastoma, using techniques such as comparative genomic hybridization (CGH),
      microsatellite analysis, conventional karyotyping, and fluorescence in situ
      hybridization (FISH). We report the use of 10K single nucleotide polymorphism
      (SNP) microarrays to detect copy number changes and allelic imbalance in six
      neuroblastoma cell lines (IMR32, SHEP, NBL-S, SJNB-1, LS, and SKNBE2c). SNP data
      were generated using the GeneChip DNA Analysis and GeneChip chromosome copy
      number software (Affymetrix). SNP arrays confirmed the presence of all previously
      reported cytogenetic abnormalities in the cell lines, including chromosome 1p
      deletion, MYCN amplification, gain of 17q and 11q, and 14q deletions. In
      addition, the SNP arrays revealed several chromosome gains and losses not
      detected by CGH or karyotyping; these included gain of 8q21.1 approximately 24.3
      and gain of chromosome 12 in IMR-32 cells; loss at 4p15.3 approximately 16.1 and
      loss at 16p12.3 approximately 13.2, 11q loss with loss of heterozygosity (LOH) at
      11q14.3 approximately 23.3 in SJNB-1 cells; and loss at 8p21.2 approximately 23.3
      and 9p21.3 approximately 22.1 with corresponding LOH in SHEP cells. The SNP
      arrays refined the mapping of the 2p amplicons in LS, BE2c, and IMR-32 cell
      lines, the 12q amplicon in LS cells, and also identified an 11q13 amplicon in LS
      cells. There was good concordance among SNP arrays, CGH, and karyotyping. SNP
      array analysis is a powerful tool for the detection of allelic imbalance in
      neuroblastoma and also allows identification of LOH without changes in copy
      number (uniparental disomy).

PMID- 17213022
TI  - Chromosomal changes associated with clinical outcome in lymph node-negative
      breast cancer.
AB  - Breast cancer is the most common malignancy among women and accounts for over one
      million new cases worldwide per year. Lymph node-negative breast cancer patients
      are reputed as having a better prognosis than lymph node-positive ones. Around
      20% of the lymph node-negative patients die within 10 years after diagnosis. To
      improve the prognostics of node-negative breast cancer, it is important to
      understand the underlying biologic mechanisms promoting survival, such as
      specific genetic changes in the tumor genome. In this study, CGH was applied to
      analyze 64 tumors from node-negative breast cancer patients to identify DNA copy
      number changes in chromosomes and chromosome regions that may be correlated to
      survival. The main findings show gains at 4q, 5q31 approximately qter, 6q12
      approximately q16, and 12q14 approximately q22, as well as losses of 17p, 18p,
      and Xq, which were significantly more recurrent in tumors from deceased patients
      than in tumors from survivors. The average number of chromosomal changes was
      higher in the tumors from deceased compared to the survivor tumors. Our findings
      suggest that tumors with specific chromosomal aberrations at 4q, 5q31
      approximately qter, 6q12 approximately q16, 12q14 approximately q22, 17p, 18p,
      and Xq result in an aggressive form of breast cancer and that these patients are
      predisposed to succumb to breast cancer.

PMID- 17213023
TI  - Cytogenetic and molecular cytogenetic findings in dedifferentiated liposarcoma
      with neural-like whorling pattern and metaplastic bone formation.
AB  - Dedifferentiated liposarcoma is a subtype of liposarcoma characterized by
      juxtaposition of well-differentiated liposarcoma with a nonadipocytic sarcoma. A
      peculiar form of dedifferentiated liposarcoma has been described, characterized
      by a nonlipogenic component with a neural-like whorling pattern of growth and
      metaplastic bone formation. We report the cytogenetic and molecular genetic
      findings of this peculiar form of dedifferentiation in a retroperitoneal tumor
      found in a 58-year-old female. The neoplasm had typical histologic findings and a
      complex karyotype characterized by several numeric and structural chromosomal
      abnormalities, including the presence of ring and giant rod chromosomes.
      Molecular cytogenetic studies found high levels of amplification of the MDM2
      oncogene, consistent with the amplification of the 12q14 chromosome band, a
      cytogenetic abnormality commonly found in these tumors. These findings indicate
      that, despite its unique and peculiar morphologic features, this unusual type of
      dedifferentiated liposarcoma shares many of the cytogenetic features and
      molecular genetic abnormalities found in other forms of dedifferentiation. The
      specific cytogenetics and molecular determinants of these peculiar morphologic
      findings, however, remain unknown.

PMID- 17213024
TI  - Novel BLIMP1/PRDM1 gene mutations in B-cell lymphoma.
AB  - B lymphocyte-induced maturation protein 1 (BLIMP1)/PR domain containing 1 with
      zinc finger domain (PRDM1) is a transcriptional repressor with a SET domain and
      Kruppel-type zinc fingers. BLIMP1/PRDM1 is expressed in a subset of germinal
      center B cells and in all plasma cells, and it is required for terminal B-cell
      differentiation. Mutations of the BLIMP1 gene have been reported in patients with
      diffuse large B-cell lymphoma. Here, we describe novel mutations in the BLIMP1
      gene in 2 of 15 (13%) cases of B-cell lymphoma (two cases of primary effusion
      lymphoma and 13 cases of diffuse large B-cell lymphoma). A tandem 10-base pair
      duplication (5'-GCTGAGTTTG-3') was found in exon 2 of the BLIMP1 gene in primary
      effusion B-cell lymphoma. We also found in diffuse large B-cell lymphoma a single
      base substitution in exon 6 (1747C-->T) that results in a somatic nonsense
      mutation (Q583X). These findings indicate that mutational analysis of the BLIMP1
      gene may be useful for characterizing the molecular basis of B-cell lymphoma.

PMID- 17213025
TI  - Acute myeloid leukemia (AML-M2) with t(5;11)(q35;q13) and normal expression of
      cyclin D1.
AB  - We report a case of acute myeloid leukemia (AML) subtype M2, with
      t(5;11)(q35;q13), in a 30-year-old man. Conventional cytogenetic, spectral
      karyotyping, and fluorescence in situ hybridization (FISH) studies on bone marrow
      sample obtained at diagnosis revealed an abnormal karyotype in all cells
      examined. FISH analysis demonstrated absence of translocations in the region of
      the cyclin D1 gene and real-time quantitative reverse transcriptase-polymerase
      chain reaction revealed normal expression of this gene. Similar to the 11q23
      region, 11q13 changes can be found in both myeloid and lymphoid neoplasias with
      different chromosomes serving as donors in translocations.

PMID- 17213026
TI  - Derivative (14)t(11;14)(q13;q32)t(11;14)(p11.2;p11.2): a novel unbalanced variant
      of the t(11;14)(q13;q32) translocation in mantle cell lymphoma.
AB  - We report the case of a 62-year-old man who presented with splenomegaly,
      leukocytosis, anemia, and thrombocytopenia. Examination of the peripheral blood,
      bone marrow, and spleen revealed involvement by mantle cell lymphoma, with some
      blastoid features and an atypical phenotype. Spleen and bone marrow classical
      chromosome analysis followed by fluorescence in situ hybridization revealed a
      novel and unusual unbalanced variant of the t(11;14)(q13;q32) translocation,
      resulting in a complex derivative chromosome harboring the IGH/CCND1 fusion gene.
      This chromosome was designated as der(14)t(11;14)(q13;q32)t(11;14)(p11.1;p11.2).

PMID- 17213027
TI  - Recurrent unbalanced whole-arm t(1;10)(q10;p10) in myelodysplastic syndrome: a
      case report and literature review.
AB  - We report a patient with myelodysplastic syndrome (refractory anemia) showing the
      karyotype 46,XY,+1,der(1;10)(q10;p10), resulting in trisomy 1q and monosomy 10q
      abnormality. This finding suggests that either trisomy of 1q or centromeric
      connection between chromosomes 1 and 10, rather than the absence of 10q, might be
      essential toward neoplastic transformation.

PMID- 17213028
TI  - Monosomy 7 as the sole abnormality of an acute basophilic leukemia.
AB  - We report the case of a 72-year-old man who had the very rare disease acute
      basophilic leukemia with the sole chromosomal finding of a monosomy 7. Most
      nuclear cells in the peripheral blood and bone marrow samples were either
      basophils or blasts. The blasts showed negative reaction with myeloperoxidase,
      periodic acid Schiff, chloroacetate esterase, alpha-naphthyl butyrate esterase,
      acid phosphatase, and Sudan black B. Metachromatic features of the blasts,
      however, were observed with toluidine blue stain. Electron microscopic evaluation
      showed the typical ultrastructure, with basophil and immature mast cell granules.
      Cytogenetic study revealed monosomy 7 in all metaphase cells, and this finding
      was confirmed by fluorescence in situ hybridization. The Philadelphia chromosome
      was absent. Review of the literature revealed abnormalities in cases of ABL. To
      our knowledge, the case reported here is the first to have basophilic leukemia
      with monosomy 7 as the only chromosome abnormality.

PMID- 17213029
TI  - IgH gene rearrangements are associated with hyperdiploid multiple myeloma in
      Korean cases: a fluorescence in situ hybridization study.

PMID- 17213030
TI  - Simultaneous presence of major secondary chromosomal abnormalities in blast
      crisis of chronic myeloid leukemia.

PMID- 17213031
TI  - A novel t(4;12)(q11;q13) in a patient with acute myeloid leukemia.

PMID- 17213032
TI  - Polymorphisms in CAG active allele length of the androgen receptor gene are not
      associated with increased risk of endometrial cancer.

PMID- 17213033
TI  - Population differences in familial adenomatous polyposis may be an expression of
      geographic differences in APC mutation pattern.

PMID- 17213034
TI  - Rise, fall and resurrection of chromosome territories: a historical perspective.
      Part II. Fall and resurrection of chromosome territories during the 1950s to
      1980s. Part III. Chromosome territories and the functional nuclear architecture:
      experiments and models from the 1990s to the present.
AB  - Part II of this historical review on the progress of nuclear architecture studies
      points out why the original hypothesis of chromosome territories from Carl Rabl
      and Theodor Boveri (described in part I) was abandoned during the 1950s and
      finally proven by compelling evidence forwarded by laser-uv-microbeam studies and
      in situ hybridization experiments. Part II also includes a section on the
      development of advanced light microscopic techniques breaking the classical Abbe
      limit written for readers with little knowledge about the present state of the
      theory of light microscopic resolution. These developments have made it possible
      to perform 3D distance measurements between genes or other specifically stained,
      nuclear structures with high precision at the nanometer scale. Moreover, it has
      become possible to record full images from fluorescent structures and perform
      quantitative measurements of their shapes and volumes at a level of resolution
      that until recently could only be achieved by electron microscopy. In part III we
      review the development of experiments and models of nuclear architecture since
      the 1990s. Emphasis is laid on the still strongly conflicting views about the
      basic principles of higher order chromatin organization. A concluding section
      explains what needs to be done to resolve these conflicts and to come closer to
      the final goal of all studies of the nuclear architecture, namely to understand
      the implications of nuclear architecture for nuclear functions.

PMID- 17213035
TI  - Nucleolus disassembly in mitosis and apoptosis: dynamic redistribution of
      phosphorylated-c-Myc, fibrillarin and Ki-67.
AB  - The nucleolus may undergo disassembly either reversibly during mitosis, or
      irreversibly in apoptosis, thus allowing the redistribution of the nucleolar
      proteins. We investigated here by immunocytochemistry the fate of three
      representative proteins, namely phosphorylated c-Myc, fibrillarin and Ki-67, and
      found that they behave independently in both processes: they relocate in distinct
      compartments during mitosis, whereas during apoptosis they may either be cleaved
      (Ki-67) or be extruded into the cytoplasm with a different kinetics and following
      an ordered, non chaotic program. The separation of these nucleolar proteins which
      occurs in early apoptotic nuclei continues also in the cytoplasm, and culminates
      in the final formation of apoptotic blebs containing different nucleolar
      proteins: this evidence confirms that the apoptotic bodies may be variable in
      size, content and surface reactivity, and include heterogeneous aggregates of
      nuclear proteins and/or nucleic acids.

PMID- 17213036
TI  - Some remarks on the use of TaqI to detect highly repetitive DNA sequences in
      human chromosomes.
AB  - In the attempt to conclude investigation of the action of restriction
      endonucleases on eukaryote chromosomes, we carried out a series of experiments
      digesting in situ human metaphase chromosomes with AluI/TaqI followed by Giemsa
      staining. We focused on the centromeric regions of chromosomes1, 2 and 16 and
      noted that those areas appeared as intensely stained blocks after AluI digestion,
      but were dramatically reduced in size or completely destroyed after subsequent
      TaqI treatment. These results permitted us to draw some conclusions on the highly
      repetitive DNA composition of these regions, in terms of alphoid and classical
      satellite DNAs.

PMID- 17213037
TI  - Immunohistochemical expression of p53, Bcl-2, COX-2, C-erb-B2, EPO-R, beta
      catenin, and E-cadherin in non tumoral gastric mucous membrane.
AB  - Different authors have investigated the immunohistochemical expression of some
      proteins in the adenocarcinoma of the stomach, including cell cycle regulators
      proteins like p53 and Bcl-2; growth factors (c-erb-B2 and EPO-R); angiogenesis
      related markers such as COX-2 and cellular adhesion molecules (beta-catenin and E
      cadherin). While these proteins have been studied in gastric adenocarcinoma,
      their immunophenotyping in non tumoral gastric mucous membrane remains
      unexplored. In the present study, we investigated the expression, function and
      behavior of these proteins in normal gastric mucous membrane to contribute to
      gain further knowledge on the significance of their loss or overexpression in
      malignant gastric tumors.

PMID- 17213038
TI  - Changes in gastric endocrine cells in Balb/c mice bearing CT-26 carcinoma cells:
      an immunohistochemical study.
AB  - The distribution and density of gastric endocrine cells in Balb/c mice bearing CT
      26 carcinoma cells were studied immunohistochemically employing specific antisera
      against serotonin, somatostatin, glucagon, gastrin, cholecystokinin (CCK)-8 and
      human pancreatic polypeptide (hPP). The animals were divided into two groups, a
      non-implanted sham group and a CT-26 carcinoma cell-implanted group. Samples were
      collected from two regions of the stomach (fundus and pylorus) at 28 days after
      implantation of the medium or the CT-26 cells (1x10(5) cells/mouse). Five of the
      6 types of immunoreactive (IR) cells were identified, with only the hPP IR cells
      not being detected. The regional distribution of the gastric endocrine cells in
      the CT-26 implanted group was similar to that of the non-implanted sham group.
      However, the endocrine cells were significantly decreased in the CT-26-implanted
      group as compared to those of the non-implanted sham group. Serotonin- and
      somatostatin-IR cells in the fundus and pylorus , and gastrin- and CCK-8-IR cells
      in the pylorus of the CT-26 implanted groups were significantly decreased
      compared to those of the sham group. In addition, glucagon-IR cells were
      restricted only to the fundus of the sham animals. hPP-IR cells were not detected
      in either the T-26 implanted- or the non-implanted group. Since endocrine cells
      are the anatomical units responsible for the production of gut hormones, a change
      in their density may reflect a change in their capacity to produce such hormones.
      Implantation of the tumor cell mass induced severe quantitative changes in
      gastric endocrine cell density, an abnormality which may contribute to the
      development of gastrointestinal symptoms, such as anorexia and indigestion,
      frequently encountered in cancer patients.

PMID- 17213039
TI  - Relationship between immunoexpression of mucin peptide cores MUC1 and MUC2 and
      Lauren's histologic subtypes of gastric carcinomas.
AB  - Lauren's system subdivides gastric cancers into an intestinal type and a diffuse
      type. This histological classification mirrors histogenetic hypotheses according
      to which the intestinal-type cancer derives from intestinal metaplasia and
      dysplasia, while the diffuse-type originates directly from gastric mucosa, with
      or without a preceding non-metaplastic dysplasia. Studies concerning mucins
      expression in gastric neoplastic and preneoplastic lesions have provided
      contradictory data concerning such histogenetic relationships. The aim of the
      present study was to verify whether a correlation between mucins phenotype and
      Lauren's classification subsists. 40 gastric adenocarcinomas, subdivided,
      according to Lauren's classification, into 27 intestinal-type, 10 diffuse-type
      and 3 unclassified cases, were examined for MUC1 and MUC2 immunohistochemical
      expression. Intestinal-type carcinomas displayed a MUC1-positive staining in
      23/27 cases and a MUC2-positive immunoreaction in 10/27 cases. Diffuse-type
      carcinomas expressed MUC1 in 3/10 and MUC2 in 8/10 cases, respectively. According
      to the mucins expression pattern, three phenotypes were identified: the gastric
      phenotype (MUC1+/MUC2-); the gastro-intestinal phenotype (MUC1+/MUC2+) and the
      intestinal phenotype (MUC1-/MUC2+). The gastric phenotype was significantly
      higherin intestinal-type adenocarcinomas, whereas cases showing an intestinal
      phenotype were significantly more frequent in diffuse-type adenocarcinomas. These
      findings provide evidence for a lack of correlation between Lauren's
      classification and MUC1 and MUC2 phenotypes. In particular, the term intestinal
      type tumour as referred to gland-forming gastric cancer does not seem to reflect
      an immunohistochemical phenotype.

PMID- 17213040
TI  - Pineal and cortical melatonin receptors MT1 and MT2 are decreased in Alzheimer's
      disease.
AB  - The pineal hormone melatonin is involved in physiological transduction of
      temporal information from the light dark cycle to circadian and seasonal
      behavioural rhythms, as well as possessing neuroprotective properties. Melatonin
      and its receptors MT1 and MT2, which belong to the family of G protein-coupled
      receptors, are impaired in Alzheimer's disease (AD) with severe consequences to
      neuropathology and clinical symptoms. The present data provides the first
      immunohistochemical evidence for the cellular localization of the both melatonin
      receptors in the human pineal gland and occipital cortex, and demonstrates their
      alterations in AD. We localized MT1 and MT2 in the pineal gland and occipital
      cortex of 7 elderly controls and 11 AD patients using immunohistochemistry with
      peroxidase-staining. In the pineal gland both MT1 and MT2 were localized to
      pinealocytes, whereas in the cortex both receptors were expressed in some
      pyramidal and non-pyramidal cells. In patients with AD, parallel to degenerative
      tissue changes, there was an overall decrease in the intensity of receptors in
      both brain regions. In line with our previous findings, melatonin receptor
      expression in AD is impaired in two additional brain areas, and may contribute to
      disease pathology.

PMID- 17213041
TI  - Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced
      pulmonary fibrosis.
AB  - To investigate simultaneously localization and relative activity of MMPs during
      extracellular matrix (ECM) remodeling in bleomycin-induced pulmonary fibrosis in
      rat, we analyzed the time course of the expression, activity and/or concentration
      of gelatinases MMP-2 and MMP-9, collagenase MMP-1, matrylisin MMP-7, TIMP-1 and
      TIMP-2, both in alveolar space (cellular and extracellular compartments) and in
      lung tissue. MMP and TIMP expression was detected (immunohistochemistry) in lung
      tissue. MMP activity (zymography) and TIMP concentration (ELISA) were evaluated
      in lung tissue homogenate (LTH), BAL supernatant (BALs) and BAL cell pellet
      (BALp) 3, 7, 14, and 28 days after bleomycin intratracheal instillation.
      Immunohistochemistry showed an extensive MMP and TIMP expression from day 7 in a
      wide range of structural and inflammatory cells in treated rats. MMP-2 was
      present mainly in epithelia, MMP-9 in inflammatory cells. MMP-2 and MMP-9
      activity was increased respectively in BAL fluid and BAL cells, with a peak at
      day 7. TIMP-1 and TIMP-2 concentration (ELISA) enhancement was delayed at day 14.
      In conclusion gelatinases and their inhibitors are significantly activated during
      bleomycin-induced pulmonary fibrosis. Marked changes in gelatinases activity are
      observed early in the alveolar compartment, with a prevailing extracellular
      activity of MMP-2 and a predominant intracellular distribution of MMP-9, while
      enzyme activity changes in lung parenchyma were less evident. In the repairing
      phase the reduction of gelatinases activity is synchronous with a peak of
      alveolar concentration of their inhibitors.

PMID- 17213042
TI  - Integrins, muscle agrin and sarcoglycans during muscular inactivity conditions:
      an immunohistochemical study.
AB  - Sarcoglycans are transmembrane proteins that seem to be functionally and
      pathologically as important as dystrophin. Sarcoglycans cluster together to form
      a complex, which is localized in the cell membrane of skeletal, cardiac, and
      smooth muscle. It has been proposed that the dystrophin-glycoprotein complex
      (DGC) links the actin cytoskeleton with the extracellular matrix and the proper
      maintenance of this connection is thought to be crucial to the mechanical
      stability of the sarcolemma. The integrins are a family of heterodimeric cell
      surface receptors which play a crucial role in cell adhesion including cell
      matrix and intracellular interactions and therefore are involved in various
      biological phenomena, including cell migration, and differentiation tissue
      repair. Sarcoglycans and integrins play a mechanical and signaling role
      stabilizing the systems during cycles of contraction and relaxation. Several
      studies suggested the possibility that integrins might play a role in muscle
      agrin signalling. On these basis, we performed an immunohistochemical analyzing
      sarcoglycans, integrins and agrin, on human skeletal muscle affected by sensitive
      motor polyneuropathy, in order to better define the correlation between these
      proteins and neurogenic atrophy due to peripheral neuropathy. Our results showed
      the existence of a cascade mechanism which provoke a loss of regulatory effects
      of muscle activity on costameres, due to loss of muscle and neural agrin. This
      cascade mechanism could determine a quantitative modification of transmembrane
      receptors and loss of alpha7B could be replaced and reinforced by enhanced
      expression of the alpha7A integrin to restore muscle fiber viability. Second, it
      is possible that the reduced cycles of contraction and relaxation of muscle
      fibers, during muscular atrophy, provoke a loss of mechanical stresses
      transmitted over cell surface receptors that physically couple the cytoskeleton
      to extracellular matrix. Consequently, these mechanical changes could determine
      modifications of chemical signals through variations of pathway structural
      integrins, and alpha7A could replace alpha7B.

PMID- 17213044
TI  - Age-specific search strategies for Medline.
AB  - BACKGROUND: Many clinicians and researchers are interested in patients of a
      specific age (childhood, geriatrics, and so on). Searching for age-specific
      publications in large bibliographic databases such as Medline is problematic
      because of inconsistencies in indexing, overlapping age categories, and the
      spread of the relevant literature over many journals. To our knowledge, no
      empirically tested age-specific search strategies exist for Medline. OBJECTIVE:
      We sought to determine the retrieval characteristics of age-specific terms in
      Medline for identifying studies relevant for five clinical specialties: adult
      medicine, geriatric medicine, pediatric medicine, neonatal medicine, and
      obstetrics. METHODS: We compared age-specific search terms and phrases for the
      retrieval of citations in Medline with a manual hand search of the literature for
      161 core health care journals. Six experienced research assistants who were
      trained and intensively calibrated read all issues of 161 journals for the
      publishing year 2000. In addition to classifying all articles for purpose and
      quality, study participants' ages were also recorded. Outcome measures were
      sensitivity, specificity, precision, and accuracy of single and combination
      search terms. RESULTS: When maximizing sensitivity, the best sensitivity and
      specificity achieved with combination terms were 98% and 81.2%, respectively, for
      pediatric medicine, 96.4% and 55.9% for geriatric medicine, 95.3% and 83.6% for
      neonatal medicine, 94.9% and 64.5% for adult medicine, and 82% and 97.1% for
      obstetrics. When specificity was maximized, all disciplines had an expected
      decrease in sensitivity and an increase in precision. Highest values for
      optimizing best sensitivity and specificity were achieved in neonatal medicine,
      92.5% and 92.6%, respectively. CONCLUSION: Selected single terms and combinations
      of MeSH terms and textwords can reliably retrieve age-specific studies cited in
      Medline.

PMID- 17213045
TI  - Web portals in primary care: an evaluation of patient readiness and willingness
      to pay for online services.
AB  - BACKGROUND: Online Web communication between physician and patient has been
      proposed by leading primary care organizations as a way to enhance physician
      patient communication, but lack of payment for this service has acted as a
      significant barrier to implementation. OBJECTIVE: This study evaluates current
      patient readiness and willingness to pay for online services in a fairly typical
      urban family medicine practice. METHODS: All patients that visited the author for
      medical care during a one-month period in the spring of 2006 were anonymously
      surveyed with a one-page survey instrument that inquired about demographics,
      willingness to pay a small annual fee for online services, the greatest fee they
      were willing to pay, and their most desired service. RESULTS: A total of 346
      patients out of 2380 active patients in the study practice (14.5%) were surveyed.
      The valid survey response rate was 95.1% (329/346.) Three quarters, or 75.4%, of
      patients had Internet access. The group with the highest access were 18- to 29
      year-olds (97%), and the group with the least access were those 70 years and up
      (56%) (P < .001). Categorized by employment, students and employed patients had
      the best access at 92% and 87%, respectively, and retirees and disabled patients
      had the worst access at 66% and 42%, respectively (P < .001). Of all patients
      with Internet access, 74.6% (n = 185) were willing to pay a small annual fee for
      one or more of the following online services: viewing of parts of their medical
      record, messaging with their physician, medication refills, appointment requests,
      and billing inquiries. Willingness to pay did not vary significantly by age (P =
      .06). Of all respondents, regardless of Internet access, 47.1% (n = 155) were
      willing to pay US $10 or more per year, with the median amount being US $20. Of
      those with Internet access (n = 248), 60.1% (n = 149) were willing to pay US $10
      or more per year, and 31% were willing to pay US $50 or more per year. The three
      most important services to patients with Internet access (n = 248), in order of
      importance, were emailing with their physician (34%), Internet viewing of their
      medical record (22%), and medication refills (11%) (P < .001). CONCLUSIONS: This
      study suggests that patients of all ages are currently ready and willing to pay a
      small annual fee for online services with their primary care physician's office.
      If 47.1% of a practice of 2500 patients each paid US $10 per year for online
      services, the annual revenue generated would be US $11775. Not only does this
      study support the economic feasibility of patient Web portals, but it suggests
      that online services could form a new line of revenue for primary care
      physicians.

PMID- 17213046
TI  - eHEALS: The eHealth Literacy Scale.
AB  - BACKGROUND: Electronic health resources are helpful only when people are able to
      use them, yet there remain few tools available to assess consumers' capacity for
      engaging in eHealth. Over 40% of US and Canadian adults have low basic literacy
      levels, suggesting that eHealth resources are likely to be inaccessible to large
      segments of the population. Using information technology for health requires
      eHealth literacy-the ability to read, use computers, search for information,
      understand health information, and put it into context. The eHealth Literacy
      Scale (eHEALS) was designed (1) to assess consumers' perceived skills at using
      information technology for health and (2) to aid in determining the fit between
      eHealth programs and consumers. OBJECTIVES: The eHEALS is an 8-item measure of
      eHealth literacy developed to measure consumers' combined knowledge, comfort, and
      perceived skills at finding, evaluating, and applying electronic health
      information to health problems. The objective of the study was to
      psychometrically evaluate the properties of the eHEALS within a population
      context. A youth population was chosen as the focus for the initial development
      primarily because they have high levels of eHealth use and familiarity with
      information technology tools. METHODS: Data were collected at baseline, post
      intervention, and 3- and 6-month follow-up using control group data as part of a
      single session, randomized intervention trial evaluating Web-based eHealth
      programs. Scale reliability was tested using item analysis for internal
      consistency (coefficient alpha) and test-retest reliability estimates. Principal
      components factor analysis was used to determine the theoretical fit of the
      measures with the data. RESULTS: A total of 664 participants (370 boys; 294
      girls) aged 13 to 21 (mean = 14.95; SD = 1.24) completed the eHEALS at four time
      points over 6 months. Item analysis was performed on the 8-item scale at
      baseline, producing a tight fitting scale with alpha = .88. Item-scale
      correlations ranged from r = .51 to .76. Test-retest reliability showed modest
      stability over time from baseline to 6-month follow-up (r = .68 to .40).
      Principal components analysis produced a single factor solution (56% of
      variance). Factor loadings ranged from .60 to .84 among the 8 items. CONCLUSIONS:
      The eHEALS reliably and consistently captures the eHealth literacy concept in
      repeated administrations, showing promise as tool for assessing consumer comfort
      and skill in using information technology for health. Within a clinical
      environment, the eHEALS has the potential to serve as a means of identifying
      those who may or may not benefit from referrals to an eHealth intervention or
      resource. Further research needs to examine the applicability of the eHEALS to
      other populations and settings while exploring the relationship between eHealth
      literacy and health care outcomes.

PMID- 17213047
TI  - Evaluating common de-identification heuristics for personal health information.
AB  - BACKGROUND: With the growing adoption of electronic medical records, there are
      increasing demands for the use of this electronic clinical data in observational
      research. A frequent ethics board requirement for such secondary use of personal
      health information in observational research is that the data be de-identified.
      De-identification heuristics are provided in the Health Insurance Portability and
      Accountability Act Privacy Rule, funding agency and professional association
      privacy guidelines, and common practice. OBJECTIVE: The aim of the study was to
      evaluate whether the re-identification risks due to record linkage are
      sufficiently low when following common de-identification heuristics and whether
      the risk is stable across sample sizes and data sets. METHODS: Two methods were
      followed to construct identification data sets. Re-identification attacks were
      simulated on these. For each data set we varied the sample size down to 30
      individuals, and for each sample size evaluated the risk of re-identification for
      all combinations of quasi-identifiers. The combinations of quasi-identifiers that
      were low risk more than 50% of the time were considered stable. RESULTS: The
      identification data sets we were able to construct were the list of all
      physicians and the list of all lawyers registered in Ontario, using 1% sampling
      fractions. The quasi-identifiers of region, gender, and year of birth were found
      to be low risk more than 50% of the time across both data sets. The combination
      of gender and region was also found to be low risk more than 50% of the time. We
      were not able to create an identification data set for the whole population.
      CONCLUSIONS: Existing Canadian federal and provincial privacy laws help explain
      why it is difficult to create an identification data set for the whole
      population. That such examples of high re-identification risk exist for
      mainstream professions makes a strong case for not disclosing the high-risk
      variables and their combinations identified here. For professional subpopulations
      with published membership lists, many variables often needed by researchers would
      have to be excluded or generalized to ensure consistently low re-identification
      risk. Data custodians and researchers need to consider other statistical
      disclosure techniques for protecting privacy.

PMID- 17213048
TI  - Evaluation of spoken dialogue technology for real-time health data collection.
AB  - BACKGROUND: A real-time assessment of patients' experiences is an important
      methodology for studies in health care, quality of life, behavioral sciences, and
      new drug and treatment development. Ecological momentary assessment is a
      methodology that allows for real-time assessment of experience and behavior in a
      subject's natural environment. Recently, electronic data collection techniques
      have been introduced, including systems utilizing interactive voice response.
      OBJECTIVE: The objective of this project was evaluation of spoken dialogue
      methodology for real-time data collection of information from patients for
      health, behavioral, and lifestyle studies and monitoring. While the management of
      the data collection process was Internet-based, this additional eHealth
      communication channel was based on over-the-phone natural language conversation
      with a dialogue system utilizing automated speech recognition technology. For
      this study we implemented a dialogue system for patients' assessment and
      monitoring of chronic pain. METHODS: Experimental evaluation of usability of the
      Pain Monitoring Voice Diary was performed with 24 volunteers. The volunteers were
      asked to contribute 10 sessions with the system over a period of 2 weeks; in
      practice, the number of sessions per subject ranged from 1 to 20. The subjects
      were asked to either relate to pain episodes in their past while answering the
      system's questions, or use as a guidance one of nine provided medical scenarios
      compiled by a pain specialist, ranging from migraines and back pain to post
      surgical pain (knee injury) and cancer- and chemotherapy-related afflictions.
      RESULTS: From 24 volunteers, we collected a total of 177 dialogue sessions: 171
      sessions were completed, while the caller hung up in the other 6 sessions. There
      were a total of 2437 dialogue turns, where a dialogue turn corresponds to one
      system prompt and one user utterance. The data capture rate, measuring the
      percentage of slots filled automatically, was 98%, while the other 2% were
      flagged for transcription. Among the utterances sent to transcription, where the
      user had opted for the "none of those" option, 70% corresponded to the "type of
      pain" slot, 20% to the "symptoms" slot, and 10% to the "body part" slot,
      indicating that those are the grammars with the highest out-of-vocabulary rate.
      CONCLUSIONS: The results of this feasibility study indicated that desired
      accuracy of data can be achieved with a high degree of automation (98% in the
      study) and that the users were indeed capable of utilizing the flexible
      interface, the sessions becoming more and more efficient as users' experience
      increased, both in terms of session duration and avoidance of troublesome
      dialogue situations.

PMID- 17213050
TI  - Review: Some evidence shows that self help books based on cognitive behaviour
      therapy can relieve depression in some patients.

PMID- 17213049
TI  - Does the quality of the working alliance predict treatment outcome in online
      psychotherapy for traumatized patients?
AB  - BACKGROUND: The provision of online counseling and online therapy is steadily
      increasing. The results of a number of controlled trials investigating the
      efficacy of online approaches indicate that some of these new treatment
      alternatives might indeed be effective. Yet, little is known about how the
      therapeutic relationship (or working alliance) evolves over the Internet and
      whether it influences treatment outcome as it does in traditional face-to-face
      therapy. The working alliance has been defined as the extent to which a patient
      and a therapist work collaboratively and purposefully and connect emotionally.
      OBJECTIVE: The aim of the study was to investigate the quality and predictive
      relevance of the therapeutic alliance for patients receiving a short-term,
      Internet-based, cognitive-behavioral therapy program for posttraumatic stress
      reactions. METHODS: After rigorous screening for exclusion criteria of high
      dissociative tendencies, risk of psychosis, and suicidal tendencies, 48 patients,
      who had experienced a traumatic event in the past, were included in the online
      treatment study. The short form of the Working Alliance Inventory (WAI-S) was
      administered at the fourth treatment session. The relevance of the therapeutic
      relationship for treatment outcome was assessed in terms of residual gain from
      pretreatment assessment to the end of treatment. The revised Impact of Event
      Scale (IES-R) and the depression and anxiety subscales of the Brief Symptom
      Inventory (BSI) were used to assess treatment outcome. RESULTS: A total of 48
      participants were included in the analysis. Overall, high alliance scores were
      found. In contrast to previous studies of conventional face-to-face therapy,
      there was only a low to modest association (.13 to .33) between the quality of
      the therapeutic relationship and treatment outcome. CONCLUSION: High alliance
      scores indicate that it was possible to establish a stable and positive
      therapeutic relationship online. However, the therapeutic relationship was found
      to be a less relevant predictor of the therapy outcome than in face-to-face
      approaches. We discuss whether this finding can be attributed to methodological
      reasons such as the restricted range of alliance ratings obtained or the time of
      administration of the WAI-S, or whether the therapeutic relationship might be
      less relevant to the treatment outcome of online therapy approaches.

PMID- 17213051
TI  - Review: Limited evidence from 2 randomised controlled trials suggests that oral
      and intramuscular vitamin B12 have similar effectiveness for vitamin B12
      deficiency.

PMID- 17213052
TI  - Low dose aspirin did not prevent cancer in healthy women.

PMID- 17213053
TI  - Vitamin E did not prevent cardiovascular disease and cancer in healthy women.

PMID- 17213054
TI  - Review: Viscosupplementation for knee osteoarthritis reduces pain and improves
      function.

PMID- 17213055
TI  - Review: Vitamin D plus calcium, but not vitamin D alone, prevents osteoporotic
      fractures in older people.

PMID- 17213056
TI  - Adjunctive treatment with eplerenone reduced 30 day all cause mortality in acute
      myocardial infarction.

PMID- 17213057
TI  - Review: Angiotensin converting enzyme inhibitors and angiotensin receptor
      blockers prevent atrial fibrillation.

PMID- 17213058
TI  - Pulmonary vein isolation was better than antiarrhythmic drugs for symptomatic
      atrial fibrillation.

PMID- 17213059
TI  - The Bug Buster kit was better than single dose pediculicides for head lice.

PMID- 17213060
TI  - Topical chloramphenicol was not effective in children with acute infective
      conjunctivitis.

PMID- 17213061
TI  - Trimethoprim reduced dysuria in women with symptoms of urinary tract infection
      but negative urine dipstick test results.

PMID- 17213062
TI  - Using exhaled NO concentrations to adjust inhaled corticosteroid dose maintained
      asthma control and reduced the dose.

PMID- 17213063
TI  - Review: Anticholinergics in addition to beta2 agonists improve outcome in
      children and adults with acute asthma.

PMID- 17213064
TI  - Review: Long term use of hormone therapy by postmenopausal women does not prevent
      chronic diseases.

PMID- 17213065
TI  - Review: Cholinesterase inhibitors may be effective in Alzheimer's disease.

PMID- 17213066
TI  - Multislice computed tomography detected coronary artery disease.

PMID- 17213067
TI  - Review: IgA endomyseal and transglutaminase antibodies had high specificity for
      diagnosis of coeliac disease.

PMID- 17213068
TI  - Age, impaired fasting glucose, and cirrhosis predicted mortality at mean 7.6
      years for non-alcoholic fatty liver disease.

PMID- 17213069
TI  - A simple risk score predicted 7 day stroke risk after transient ischaemic attack.

PMID- 17213070
TI  - The GATE frame: critical appraisal with pictures.

PMID- 17213071
TI  - Teaching tip: balloons and teddy bears.

PMID- 17213072
TI  - Amlodipine plus perindopril was better than atenolol plus bendroflumethiazide for
      reducing complications in hypertension.

PMID- 17213073
TI  - Review: aspirin plus warfarin decreases cardiovascular morbidity with an increase
      in major bleeding in acute coronary syndromes.

PMID- 17213074
TI  - First line treatment with colchicine reduced recurrent pericarditis.

PMID- 17213075
TI  - Review: long term anticoagulation reduces recurrent venous thromboembolism.

PMID- 17213076
TI  - Glargine dose titration by patients and physicians was equally effective for
      preventing severe hypoglycaemia.

PMID- 17213077
TI  - Pioglitazone did not reduce macrovascular complications and increased HF in type
      2 diabetes with macrovascular disease.

PMID- 17213079
TI  - Identifying hospice-appropriate nursing home residents for physicians increased
      hospice referrals and enrollment.

PMID- 17213078
TI  - Review: self help interventions for smoking cessation are not effective unless
      tailored to the individual.

PMID- 17213080
TI  - A centralised telephone intervention reduced combined all cause mortality or
      admission for worsening HF in chronic heart failure.

PMID- 17213081
TI  - The 5 component acellular pertussis vaccine combined with tetanus and diphtheria
      toxoids was efficacious in adolescents and adults.

PMID- 17213082
TI  - Parenteral artesunate reduced inhospital mortality more than quinine in severe
      falciparum malaria.

PMID- 17213083
TI  - Review: 6 RCTs show similar efficacy and safety for continuous dosing and 28 day
      combination contraceptive pills.

PMID- 17213084
TI  - Review: lorazepam provides the best control for status epilepticus.

PMID- 17213085
TI  - Review: wearing graduated compression stockings during air travel reduces the
      risk of deep venous thromboembolism.

PMID- 17213086
TI  - Review: the Wells rule is more useful than individual clinical features for
      predicting risk of deep venous thrombosis.

PMID- 17213087
TI  - The Wells rule was not useful in ruling out deep venous thrombosis in a primary
      care setting.

PMID- 17213088
TI  - Review: medical history, physical examination, and routine tests are useful for
      diagnosing heart failure in dyspnoea.

PMID- 17213089
TI  - Male sex, first idiopathic deep venous thrombosis, and oral contraception were
      risk factors for recurrent venous thrombotic events.

PMID- 17213090
TI  - Cognitive therapy in addition to standard care was more cost effective than
      standard care alone in bipolar disorder.

PMID- 17213091
TI  - The Canadian CT Head Rule reduced the need for CT scans more than the New Orleans
      Criteria in minor head injury.

PMID- 17213092
TI  - Why fair tests are needed: a brief history.

PMID- 17213093
TI  - Was the study big enough? Two cafe rules.

PMID- 17213094
TI  - Review: Medical history, physical examination, and routine tests are useful for
      diagnosing heart failure in dyspnoea.

PMID- 17213095
TI  - Watchful waiting was as safe as surgical repair for minimally symptomatic
      inguinal hernias.

PMID- 17213096
TI  - Review: Empirical atypical coverage does not reduce mortality in hospitalised
      patients with community acquired pneumonia.

PMID- 17213097
TI  - Review: Oxytocin receptor antagonists for preterm labour do not improve infant
      outcomes more than placebo or other tocolytics.

PMID- 17213098
TI  - Oestrogen did not improve health related quality of life in postmenopausal women
      with hysterectomy.

PMID- 17213099
TI  - Inhaled insulin added onto or replacing 2 oral agents reduced haemoglobin A1c
      concentrations in type 2 diabetes.

PMID- 17213100
TI  - Self treatment after Epley procedure was effective for benign paroxysmal
      positional vertigo of the posterior semicircular canal.

PMID- 17213101
TI  - Prednisolone plus a disease modifying antirheumatic drug improved outcomes in
      early rheumatoid arthritis.

PMID- 17213102
TI  - Improved access to emergency contraception did not increase risky sexual
      behaviour in adolescents.

PMID- 17213103
TI  - Olanzapine led to fewer withdrawals than other antipsychotic drugs but increased
      weight gain, glucose, and lipids.

PMID- 17213104
TI  - Addition of clopidogrel to aspirin, but not early use of metoprolol, improved
      overall outcome in acute myocardial infarction.

PMID- 17213105
TI  - Review: Cardioselective beta blockers do not produce adverse respiratory effects
      in COPD.

PMID- 17213106
TI  - Review: Beta blockers are less effective than other antihypertensive drugs for
      reducing risk of stroke in primary hypertension.

PMID- 17213107
TI  - Long term fenofibrate did not reduce major coronary events but may reduce total
      CVD events in type 2 diabetes.

PMID- 17213108
TI  - Review: Secondary prevention programmes with and without exercise reduce all
      cause mortality and recurrent MI.

PMID- 17213109
TI  - A handwashing intervention in a low income community in the developing world
      reduced disease incidence in children.

PMID- 17213110
TI  - Low dose iron supplementation was effective in older patients with iron
      deficiency anaemia.

PMID- 17213111
TI  - The Thessaly test at 20 degrees of knee flexion accurately detected meniscal
      tears.

PMID- 17213112
TI  - Dyspnoea at cardiac stress testing was associated with an increased risk of death
      in symptomatic and asymptomatic people.

PMID- 17213113
TI  - Review: Care assisted by nurses or pharmacists provides better blood pressure
      control.

PMID- 17213114
TI  - Evaluating evidence-based practice performance.

PMID- 17213116
TI  - Review: Self monitoring increases the efficacy and safety of anticoagulant
      therapy.

PMID- 17213115
TI  - The EBM journal selection process: how to find the 1 in 400 valid and highly
      relevant new research articles.

PMID- 17213117
TI  - Lowering homocysteine with folic acid and B vitamins did not prevent vascular
      events in vascular disease.

PMID- 17213118
TI  - Lowering homocysteine with folic acid and B vitamins did not prevent vascular
      events after myocardial infarction.

PMID- 17213119
TI  - Review: Surgery is not effective for obstructive sleep apnoea hypopnoea syndrome
      in adults.

PMID- 17213120
TI  - Below the elbow casts were as effective as above the elbow casts for maintaining
      reduction of forearm fractures in children.

PMID- 17213121
TI  - Wet wrap bandages for 4 weeks did not differ from topical ointments but increased
      skin infections in paediatric atopic eczema.

PMID- 17213122
TI  - A low fat diet led to a minor weight loss at 7.5 years in postmenopausal women.

PMID- 17213123
TI  - Review: Sedative hypnotics increase adverse effects more than they improve sleep
      quality in older persons with insomnia.

PMID- 17213124
TI  - Maintenance treatment with paroxetine, but not psychotherapy, prevented recurrent
      major depression in older people.

PMID- 17213125
TI  - Rapid access to methadone improved entry and outcomes in heroin addicts awaiting
      methadone treatment.

PMID- 17213126
TI  - A rotavirus vaccine for infants prevented rotavirus gastroenteritis with no
      increase in risk of intussusception.

PMID- 17213127
TI  - Mometasone furoate nasal spray was more effective for symptom relief of acute
      rhinosinusitis than amoxicillin or placebo.

PMID- 17213128
TI  - Glucosamine and chondroitin sulphate did not improve pain in osteoarthritis of
      the knee.

PMID- 17213129
TI  - Review: Self report of hearing loss and the whispered voice test are useful for
      screening for hearing impairment.

PMID- 17213130
TI  - Review: ECG, BNP, and N terminal-pro BNP are more sensitive than specific for
      chronic left ventricular systolic dysfunction.

PMID- 17213131
TI  - 71% of patients with newly diagnosed chronic kidney disease progressed to renal
      replacement therapy or death within 3 years.

PMID- 17213132
TI  - Review: The Wells clinical prediction guide and D-dimer testing predict deep vein
      thrombosis.

PMID- 17213133
TI  - The Outpatient Bleeding Risk Index predicted major bleeding in patients taking
      warfarin.

PMID- 17213134
TI  - A simple prediction rule identified patients with pulmonary embolism at low risk
      of short term death.

PMID- 17213135
TI  - The World Health Organization clinical decision rule was specific but not
      sensitive for predicting group A beta haemolytic streptococcus in children with
      pharyngitis.

PMID- 17213136
TI  - Making sense of diagnostic tests likelihood ratios.

PMID- 17213138
TI  - Why is evidence-based medicine important?

PMID- 17213137
TI  - Simplified calculations using likelihood ratios.

PMID- 17213139
TI  - Telephone care was more effective than standard care for smoking cessation in
      daily smokers.

PMID- 17213140
TI  - Combined budesonide and formoterol for maintenance and relief provided better
      asthma control than budesonide for maintenance and terbutaline for relief.

PMID- 17213141
TI  - Addition of salmeterol to usual asthma pharmacotherapy may increase respiratory
      related deaths or life threatening experiences.

PMID- 17213142
TI  - Review: vaccines prevent influenza and influenza-like illness in healthy children
      >2 years of age.

PMID- 17213143
TI  - Review: antiviral agents reduce the risk of influenza in healthy adults and
      alleviate symptoms faster than placebo.

PMID- 17213144
TI  - Delivery of 100%, 40%, and blow-by humidity did not differ for change in croup
      scores in children with moderate croup.

PMID- 17213145
TI  - Clopidogrel plus aspirin did not differ from aspirin alone for reducing MI,
      stroke, and CV death in high risk atherothrombosis.

PMID- 17213147
TI  - Review: the renoprotective effects of ACE inhibitors and ARBs independent of
      blood pressure control are uncertain.

PMID- 17213146
TI  - Review: ACE inhibitors delay microalbuminuria in diabetes without nephropathy and
      reduce mortality in diabetic nephropathy.

PMID- 17213148
TI  - Laparoscopic surgery was better than an intensive non-surgical intervention for
      weight loss in mild to moderate obesity.

PMID- 17213149
TI  - Review: behaviour therapy is effective for insomnia.

PMID- 17213150
TI  - Black cohosh and St John's wort reduced climacteric and depressive symptoms.

PMID- 17213151
TI  - Calcium did not prevent fractures in elderly women.

PMID- 17213152
TI  - Review: sparse evidence supports lifestyle modifications for reducing symptoms of
      gastro-oesophageal reflux disease.

PMID- 17213153
TI  - Review: topical quinolones are better than systemic antibiotics for chronic
      suppurative otitis media at up to 2 weeks.

PMID- 17213154
TI  - Response to a 2 week continuous positive airway pressure trial accurately
      identified patients with obstructive sleep apnoea syndrome.

PMID- 17213155
TI  - Review: computed tomographic colonography is accurate for medium and large
      colorectal polyps and cancer.

PMID- 17213156
TI  - Albumin to creatinine ratio in 2 random urine samples was an accurate screening
      test for albuminuria in diabetic pregnancies.

PMID- 17213157
TI  - Review: magnetic resonance imaging alone is of limited usefulness in diagnosing
      multiple sclerosis.

PMID- 17213158
TI  - Physical exertion at work during pregnancy did not increase risk of preterm
      delivery or fetal growth restriction.

PMID- 17213159
TI  - Of studies, syntheses, synopses, summaries, and systems: the "5S" evolution of
      information services for evidence-based healthcare decisions.

PMID- 17213162
TI  - Review: Beta blockers differ in their efficacy for preventing major
      cardiovascular events in younger and older patients.

PMID- 17213163
TI  - Aspirin plus dipyridamole was more effective than aspirin alone for preventing
      vascular events after minor cerebral ischaemia.

PMID- 17213164
TI  - Clopidogrel plus aspirin was inferior to oral anticoagulation for preventing
      vascular events in atrial fibrillation.

PMID- 17213165
TI  - Review: Selective COX 2 inhibitors increase vascular events more than placebo and
      naproxen but not more than other NSAIDs.

PMID- 17213166
TI  - Long term dietary use of potassium enriched salt reduced cardiovascular death in
      elderly men.

PMID- 17213167
TI  - Sublingual immunotherapy with a grass allergen tablet improved symptoms and
      quality of life in allergic rhinoconjunctivitis.

PMID- 17213168
TI  - 2 year inhaled corticosteroid therapy did not prevent asthma in high risk
      preschool children after treatment was discontinued.

PMID- 17213169
TI  - Esomeprazole did not universally improve asthma outcomes in moderate to severe
      stable asthma.

PMID- 17213170
TI  - Adjunctive inhaled insulin before meals improved glycaemic control more than
      adjunctive metformin in type 2 diabetes mellitus.

PMID- 17213171
TI  - Raloxifene and tamoxifen had similar efficacy for preventing invasive breast
      cancer in women at increased risk.

PMID- 17213172
TI  - Raloxifene produced both harms and benefits in postmenopausal women, with no
      reduction in cardiovascular disease risk.

PMID- 17213173
TI  - A self help guidebook reduced primary care consultations in irritable bowel
      syndrome.

PMID- 17213174
TI  - Review: Antibiotic therapy leads to slightly earlier recovery in acute bacterial
      conjunctivitis.

PMID- 17213175
TI  - A single dose of azithromycin was more effective than ciprofloxacin for severe
      cholera in men in Bangladesh.

PMID- 17213176
TI  - Review: Surgery is more effective than medical treatment for heavy menstrual
      bleeding but quality of life results are similar.

PMID- 17213177
TI  - Dental restoration with amalgam was not worse than resin composite material for
      children's health.

PMID- 17213178
TI  - The GAD-7 scale was accurate for diagnosing generalised anxiety disorder.

PMID- 17213179
TI  - 1 year mortality after first hospital admission for heart failure was similar in
      patients with preserved or reduced ejection fraction.

PMID- 17213180
TI  - The San Francisco Syncope Rule was useful for stratifying risk in emergency
      department patients with syncope.

PMID- 17213181
TI  - Chronic cough in children had various aetiologies and common causes of adult
      cough were found in <10% of children.

PMID- 17213183
TI  - Coordinate regulation of phospholipid biosynthesis and secretory pathway gene
      expression in XBP-1(S)-induced endoplasmic reticulum biogenesis.
AB  - Development of the expansive endoplasmic reticulum (ER) present in specialized
      secretory cell types requires X-box-binding protein-1 (Xbp-1). Enforced
      expression of XBP-1(S), a transcriptional activator generated by unfolded protein
      response-mediated splicing of Xbp-1 mRNA, is sufficient to induce proliferation
      of rough ER. We previously showed that XBP-1(S)-induced ER biogenesis in
      fibroblasts correlates with increased production of phosphatidylcholine (PtdCho),
      the primary phospholipid of the ER membrane, and enhanced activities of the
      choline cytidylyltransferase (CCT) and cholinephosphotransferase enzymes in the
      cytidine diphosphocholine (CDP-choline) pathway of PtdCho biosynthesis. Here, we
      report that the level and synthesis of CCT, the rate-limiting enzyme in the CDP
      choline pathway, is elevated in fibroblasts overexpressing XBP-1(S). Furthermore,
      overexpression experiments demonstrated that raising the activity of CCT, but not
      cholinephosphotransferase, is sufficient to augment PtdCho biosynthesis in
      fibroblasts, indicating that XBP-1(S) increases the output of the CDP-choline
      pathway primarily via its effects on CCT. Finally, fibroblasts overexpressing CCT
      up-regulated PtdCho synthesis to a level similar to that in XBP-1(S)-transduced
      cells but exhibited only a small increase in rough ER and no induction of
      secretory pathway genes. The more robust XBP-1(S)-induced ER expansion was
      accompanied by induction of a wide array of genes encoding proteins that function
      either in the ER or at other steps in the secretory pathway. We propose that XBP
      1(S) regulates ER abundance by coordinately increasing the supply of membrane
      phospholipids and ER proteins, the key ingredients for ER biogenesis.

PMID- 17213184
TI  - Identification of a novel domain at the N terminus of caveolin-1 that controls
      rear polarization of the protein and caveolae formation.
AB  - When cells are migrating, caveolin-1, the principal protein component of
      caveolae, is excluded from the leading edge and polarized at the cell rear. The
      dynamic feature depends on a specific sequence motif that directs intracellular
      trafficking of the protein. Deletion mutation analysis revealed a putative
      polarization domain at the N terminus of caveolin-1, between amino acids 32-60.
      Alanine substitution identified a minimal sequence of 10 residues
      ((46)TKEIDLVNRD(55)) necessary for caveolin-1 rear polarization. Interestingly,
      deletion of amino acids 1-60 did not prevent the polarization of caveolin-1 in
      human umbilical vein endothelial cells or wild-type mouse embryonic fibroblasts
      because of an interaction of Cav(61-178) mutant with endogenous caveolin-1.
      Surprisingly, expression of the depolarization mutant in caveolin-1 null cells
      dramatically impeded caveolae formation. Furthermore, knockdown of caveolae
      formation by methyl-beta-cyclodextrin failed to prevent wild-type caveolin-1 rear
      polarization. Importantly, genetic depletion of caveolin-1 led to disoriented
      migration, which can be rescued by full-length caveolin-1 but not the
      depolarization mutant, indicating a role of caveolin-1 polarity in chemotaxis.
      Thus, we have identified a sequence motif that is essential for caveolin-1 rear
      polarization and caveolae formation.

PMID- 17213185
TI  - 13C and 1H NMR studies of ionizations and hydrogen bonding in chymotrypsin
      glyoxal inhibitor complexes.
AB  - Benzyloxycarbonyl (Z)-Ala-Pro-Phe-glyoxal and Z-Ala-Ala-Phe-glyoxal have both
      been shown to be inhibitors of alpha-chymotrypsin with minimal Ki values of 19
      and 344 nM, respectively, at neutral pH. These Ki values increased at low and
      high pH with pKa values of approximately 4.0 and approximately 10.5,
      respectively. By using surface plasmon resonance, we show that the apparent
      association rate constant for Z-Ala-Pro-Phe-glyoxal is much lower than the value
      expected for a diffusion-controlled reaction. 13C NMR has been used to show that
      at low pH the glyoxal keto carbon is sp3-hybridized with a chemical shift of
      approximately 100.7 ppm and that the aldehyde carbon is hydrated with a chemical
      shift of approximately 91.6 ppm. The signal at approximately 100.7 ppm is
      assigned to the hemiketal formed between the hydroxy group of serine 195 and the
      keto carbon of the glyoxal. In a slow exchange process controlled by a pKa of
      approximately 4.5, the aldehyde carbon dehydrates to give a signal at
      approximately 205.5 ppm and the hemiketal forms an oxyanion at approximately
      107.0 ppm. At higher pH, the re-hydration of the glyoxal aldehyde carbon leads to
      the signal at 107 ppm being replaced by a signal at 104 ppm (pKa approximately
      9.2). On binding either Z-Ala-Pro-Phe-glyoxal or Z-Ala-Ala-Phe-glyoxal to alpha
      chymotrypsin at 4 and 25 degrees C, 1H NMR is used to show that the binding of
      these glyoxal inhibitors raises the pKa value of the imidazolium ion of histidine
      57 to a value of >11 at both 4 and 25 degrees C. We discuss the mechanistic
      significance of these results, and we propose that it is ligand binding that
      raises the pKa value of the imidazolium ring of histidine 57 allowing it to
      enhance the nucleophilicity of the hydroxy group of the active site serine 195
      and lower the pKa value of the oxyanion forming a zwitterionic tetrahedral
      intermediate during catalysis.

PMID- 17213182
TI  - Identification of genes related to Parkinson's disease using expressed sequence
      tags.
AB  - In a search for novel target genes related to Parkinson's disease (PD), two full
      length cDNA libraries were constructed from a human normal substantia nigra (SN)
      and a PD patient's SN. An analysis of the gene expression profiles between them
      was done using the expressed sequence tags (ESTs) frequency. Data for the
      differently expressed genes were verified by quantitative real-time RT-PCR,
      immunohistochemical analysis and a cell death assay. Among the 76 genes
      identified with a significant difference (P > 0.9), 21 upregulated genes and 13
      downregulated genes were confirmed to be differentially expressed in human PD
      tissues and/or in an MPTP-treated mice model by quantitative real-time RT-PCR.
      Among those genes, an immunohistochemical analysis using an MPTP mice model for
      alpha-tubulin including TUBA3 and TUBA6 showed that the protein levels are
      downregulated, as well as the RNA levels. In addition, MBP, PBP and GNAS were
      confirmed to accelerate cell death activity, whereas SPP1 and TUBA3 to retard
      this process. Using an analysis of ESTs frequency, it was possible to identify a
      large number of genes related to human PD. These new genes, MBP, PBP, GNAS, SPP1
      and TUBA3 in particular, represent potential biomarkers for PD and could serve as
      useful targets for elucidating the molecular mechanisms associated with PD.

PMID- 17213186
TI  - alpha5 integrin signaling regulates the formation of spines and synapses in
      hippocampal neurons.
AB  - The actin-based dynamics of dendritic spines play a key role in synaptic
      plasticity, which underlies learning and memory. Although it is becoming
      increasingly clear that modulation of actin is critical for spine dynamics, the
      upstream molecular signals that regulate the formation and plasticity of spines
      are poorly understood. In non-neuronal cells, integrins are critical modulators
      of the actin cytoskeleton, but their function in the nervous system is not well
      characterized. Here we show that alpha5 integrin regulates spine morphogenesis
      and synapse formation in hippocampal neurons. Knockdown of alpha5 integrin
      expression using small interfering RNA decreased the number of dendritic
      protrusions, spines, and synapses. Expression of constitutively active or
      dominant negative alpha5 integrin also resulted in alterations in the number of
      dendritic protrusions, spines, and synapses. alpha5 integrin signaling regulates
      spine morphogenesis and synapse formation by a mechanism that is dependent on Src
      kinase, Rac, and the signaling adaptor GIT1. Alterations in the activity or
      localization of these molecules result in a significant decrease in the number of
      spines and synapses. Thus, our results point to a critical role for integrin
      signaling in regulating the formation of dendritic spines and synapses in
      hippocampal neurons.

PMID- 17213187
TI  - Dimer structure of an interfacially impaired phosphatidylinositol-specific
      phospholipase C.
AB  - The crystal structure of the W47A/W242A mutant of phosphatidylinositol-specific
      phospholipase C (PI-PLC) from Bacillus thuringiensis has been solved to 1.8A
      resolution. The W47A/W242A mutant is an interfacially challenged enzyme, and it
      has been proposed that one or both tryptophan side chains serve as membrane
      interfacial anchors (Feng, J., Wehbi, H., and Roberts, M. F. (2002) J. Biol.
      Chem. 277, 19867-19875). The crystal structure supports this hypothesis. Relative
      to the crystal structure of the closely related (97% identity) wild-type PI-PLC
      from Bacillus cereus, significant conformational differences occur at the
      membrane-binding interfacial region rather than the active site. The Trp --> Ala
      mutations not only remove the membrane-partitioning aromatic side chains but also
      perturb the conformations of the so-called helix B and rim loop regions, both of
      which are implicated in interfacial binding. The crystal structure also reveals a
      homodimer, the first such observation for a bacterial PI-PLC, with pseudo-2-fold
      symmetry. The symmetric dimer interface is stabilized by hydrophobic and hydrogen
      bonding interactions, contributed primarily by a central swath of aromatic
      residues arranged in a quasiherringbone pattern. Evidence that interfacially
      active wild-type PI-PLC enzymes may dimerize in the presence of
      phosphatidylcholine vesicles is provided by fluorescence quenching of PI-PLC
      mutants with pyrene-labeled cysteine residues. The combined data suggest that
      wild-type PI-PLC can form similar homodimers, anchored to the interface by the
      tryptophan and neighboring membrane-partitioning residues.

PMID- 17213188
TI  - Regulation of the nuclear poly(A)-binding protein by arginine methylation in
      fission yeast.
AB  - Two structurally different poly(A)-binding proteins (PABP) bind the poly(A) tract
      of mRNAs in most mammalian cells: PABPC in the cytoplasm and PABP2/PABPN1 in the
      nucleus. Whereas yeast orthologs of the cytoplasmic PABP are characterized, a
      gene product homologous to mammalian PABP2 has not been identified in yeast. We
      report here the identification of a homolog of PABP2 as an arginine
      methyltransferase 1 (RMT1)-associated protein in fission yeast. The product of
      the Schizosaccharomyces pombe pab2 gene encodes a nonessential nuclear protein
      and demonstrates specific poly(A) binding in vitro. Consistent with a functional
      role in poly(A) tail metabolism, mRNAs from pab2-null cells displayed
      hyperadenylated 3'-ends. We also show that arginine residues within the C
      terminal arginine-rich domain of Pab2 are modified by RMT1-dependent methylation.
      Whereas the arginine methylated and unmethylated forms of Pab2 behaved similarly
      in terms of subcellular localization, poly(A) binding, and poly(A) tail length
      control; Pab2 oligomerization levels were markedly increased when Pab2 was not
      methylated. Significantly, Pab2 overexpression reduced growth rate, and this
      growth inhibitory effect was exacerbated in rmt1-null cells. Our results indicate
      that the main cellular function of Pab2 is in poly(A) tail length control and
      support a biological role for arginine methylation in the regulation of Pab2
      oligomerization.

PMID- 17213189
TI  - Ca2+ Activation kinetics of the two aspartate-glutamate mitochondrial carriers,
      aralar and citrin: role in the heart malate-aspartate NADH shuttle.
AB  - Ca(2+) regulation of the Ca(2+) binding mitochondrial carriers for
      aspartate/glutamate (AGCs) is provided by their N-terminal extensions, which face
      the intermembrane space. The two mammalian AGCs, aralar and citrin, are members
      of the malate-aspartate NADH shuttle. We report that their N-terminal extensions
      contain up to four pairs of EF-hand motifs plus a single vestigial EF-hand, and
      have no known homolog. Aralar and citrin contain one fully canonical EF-hand pair
      and aralar two additional half-pairs, in which a single EF-hand is predicted to
      bind Ca(2+). Shuttle activity in brain or skeletal muscle mitochondria, which
      contain aralar as the major AGC, is activated by Ca(2+) with S(0.5) values of 280
      350 nm; higher than those obtained in liver mitochondria (100-150 nm) that
      contain citrin as the major AGC. We have used aralar- and citrin-deficient mice
      to study the role of the two isoforms in heart, which expresses both AGCs. The
      S(0.5) for Ca(2+) activation of the shuttle in heart mitochondria is about 300
      nm, and it remains essentially unchanged in citrin-deficient mice, although it
      undergoes a drastic reduction to about 100 nm in aralar-deficient mice.
      Therefore, aralar and citrin, when expressed as single isoforms in heart, confer
      differences in Ca(2+) activation of shuttle activity, probably associated with
      their structural differences. In addition, the results reveal that the two AGCs
      fully account for shuttle activity in mouse heart mitochondria and that no other
      glutamate transporter can replace the AGCs in this pathway.

PMID- 17213190
TI  - Multiple residues in the second extracellular loop are critical for M3 muscarinic
      acetylcholine receptor activation.
AB  - Recent studies suggest that the second extracellular loop (o2 loop) of bovine
      rhodopsin and other class I G protein-coupled receptors (GPCRs) targeted by
      biogenic amine ligands folds deeply into the transmembrane receptor core where
      the binding of cis-retinal and biogenic amine ligands is known to occur. In the
      past, the potential role of the o2 loop in agonist-dependent activation of
      biogenic amine GPCRs has not been studied systematically. To address this issue,
      we used the M(3) muscarinic acetylcholine receptor (M3R), a prototypic class I
      GPCR, as a model system. Specifically, we subjected the o2 loop of the M3R to
      random mutagenesis and subsequently applied a novel yeast genetic screen to
      identity single amino acid substitutions that interfered with M3R function. This
      screen led to the recovery of about 20 mutant M3Rs containing single amino acid
      changes in the o2 loop that were inactive in yeast. In contrast, application of
      the same strategy to the extracellular N-terminal domain of the M3R did not yield
      any single point mutations that disrupted M3R function. Pharmacological
      characterization of many of the recovered mutant M3Rs in mammalian cells,
      complemented by site-directed mutagenesis studies, indicated that the presence of
      several o2 loop residues is important for efficient agonist-induced M3R
      activation. Besides the highly conserved Cys(220) residue, Gln(207), Gly(211),
      Arg(213), Gly(218), Ile(222), Phe(224), Leu(225), and Pro(228) were found to be
      of particular functional importance. In general, mutational modification of these
      residues had little effect on agonist binding affinities. Our findings are
      therefore consistent with a model in which multiple o2 loop residues are involved
      in stabilizing the active state of the M3R. Given the high degree of structural
      homology found among all biogenic amine GPCRs, our findings should be of
      considerable general relevance.

PMID- 17213191
TI  - Skeletal muscle atrophy, a link between depression of protein synthesis and
      increase in degradation.
AB  - Both proteolysis-inducing factor (PIF) and angiotensin II have been shown to
      produce a depression in protein synthesis in murine myotubes concomitant with an
      increased phosphorylation of eukaryotic initiation factor 2 (eIF2alpha). Both PIF
      and angiotensin II were shown to induce autophosphorylation of the RNA-dependent
      protein kinase (PKR), and an inhibitor of this enzyme completely attenuated the
      depression in protein synthesis and prevented the induction of eIF2alpha
      phosphorylation. The PKR inhibitor also completely attenuated the increase in
      protein degradation induced by PIF and angiotensin II and prevented the increase
      in proteasome expression and activity. To confirm these results myotubes were
      transfected with plasmids that express either wild-type PKR, or a catalytically
      inactive PKR variant, PKRDelta6. Myotubes expressing PKRDelta6 showed no increase
      in eIF2alpha phosphorylation in response to PIF or angiotensin II, no depression
      in protein synthesis, and no increase in protein degradation or increase in
      proteasome expression. Induction of the ubiquitin-proteasome pathway by PIF and
      angiotensin II has been linked to activation of the transcription factor nuclear
      factor-kappaB (NF-kappaB). Inhibition of PKR prevented nuclear migration of NF
      kappaB in response to both PIF and angiotensin II, by preventing degradation of
      the inhibitor protein I-kappaB. Phosphorylation of PKR and eIF2alpha was also
      significantly increased in the gastrocnemius muscle of weight losing mice bearing
      the MAC16 tumor, suggesting that a similar process may be operative in cancer
      cachexia. These results provide a link between the depression of protein
      synthesis in skeletal muscle and the increase in protein degradation.

PMID- 17213192
TI  - Crystal structure and function of the zinc uptake regulator FurB from
      Mycobacterium tuberculosis.
AB  - Members of the ferric/zinc uptake regulator (Fur/Zur) family are the central
      metal-dependent regulator proteins in many Gram-negative and -positive bacteria.
      They are responsible for the control of a wide variety of basic physiological
      processes and the expression of important virulence factors in human pathogens.
      Therefore, Fur has gathered significant interest as a potential target for novel
      antibiotics. Here we report the crystal structure of FurB from Mycobacterium
      tuberculosis at a resolution of 2.7A, and we present biochemical and
      spectroscopic data that allow us to propose the functional role of this protein.
      Although the overall fold of FurB with an N-terminal DNA binding domain and a C
      terminal dimerization domain is conserved among the Zur/Fur family, large
      differences in the spatial arrangement of the two domains with respect to each
      other can be observed. The biochemical and spectroscopic analysis presented here
      reveals that M. tuberculosis FurB is Zn(II)-dependent and is likely to control
      genes involved in the bacterial zinc uptake. The combination of the structural,
      spectroscopic, and biochemical results enables us to determine the structural
      basis for functional differences in this important family of bacterial
      regulators.

PMID- 17213193
TI  - Cooperativity in cytochrome P450 3A4: linkages in substrate binding, spin state,
      uncoupling, and product formation.
AB  - Understanding the detailed metabolic mechanisms of membrane-associated
      cytochromes P450 is often hampered by heterogeneity, ill-defined oligomeric state
      of the enzyme, and variation in the stoichiometry of the functional
      P450.reductase complexes in various reconstituted systems. Here, we describe the
      detailed characterization of a functionally homogeneous 1:1 complex of cytochrome
      P450 3A4 (CYP3A4) and cytochrome P450 reductase solubilized via self-assembly in
      a nanoscale phospholipid bilayer. CYP3A4 in this complex showed a nearly complete
      conversion from the low- to high-spin state when saturated with testosterone (TS)
      and no noticeable modulation due to the presence of cytochrome P450 reductase.
      Global analysis of equilibrium substrate binding and steady-state NADPH
      consumption kinetics provided precise resolution of the fractional contributions
      to turnover of CYP3A4 intermediates with one, two, or three TS molecules bound.
      The first binding event accelerates NADPH consumption but does not result in
      significant product formation due to essentially complete uncoupling. Binding of
      the second substrate molecule is critically important for catalysis, as the
      product formation rate reaches a maximum value with two TS molecules bound,
      whereas the third binding event significantly improves the coupling efficiency of
      redox equivalent usage with no further increase in product formation rate. The
      resolution of the fractional contributions of binding intermediates of CYP3A4
      into experimentally observed overall spin shift and the rates of steady-state
      NADPH oxidation and product formation provide new detailed insight into the
      mechanisms of cooperativity and allosteric regulation in this human cytochrome
      P450.

PMID- 17213194
TI  - A bipartite sequence motif induces translation reinitiation in feline calicivirus
      RNA.
AB  - The mechanism leading to reinitiation of translation after termination of protein
      synthesis in eukaryotes has not yet been resolved in detail. One open question
      concerns the way the post-termination ribosome is tethered to the mRNA to allow
      binding of the necessary initiation factors. In caliciviruses, a family of
      positive strand RNA viruses, the capsid protein VP2 is translated via a
      termination/reinitiation process. VP2 of the feline calicivirus is encoded in the
      3'-terminal open reading frame 3 (ORF3) that overlaps with the preceding ORF2 by
      four nucleotides. In transient expression studies, the efficiency of VP2
      expression was 20 times lower than that of the ORF2 proteins. The close vicinity
      of the ORF2 termination signal and the ORF3 AUG codon was crucial, whereas the
      AUG could be replaced by alternative codons. Deletion mapping revealed that the
      3'-terminal 69 nucleotides of ORF2 are crucial for VP2 expression. This sequence
      contains two essential sequence motifs. The first motif is conserved among
      caliciviruses and complementary to part of the 18 S rRNA. In conclusion, VP2 is
      expressed in a translation termination/reinitiation process that is special
      because it requires a sequence element that could prevent dissociation of post
      termination ribosomes via hybridization with 18 S rRNA.

PMID- 17213195
TI  - Phospholipid biosynthesis program underlying membrane expansion during B
      lymphocyte differentiation.
AB  - Stimulated B-lymphocytes differentiate into plasma cells committed to antibody
      production. Expansion of the endoplasmic reticulum and Golgi compartments is a
      prerequisite for high rate synthesis, assembly, and secretion of immunoglobulins.
      The bacterial cell wall component lipopolysaccharide (LPS) stimulates murine B
      cells to proliferate and differentiate into antibody-secreting cells that
      morphologically resemble plasma cells. LPS activation of CH12 B-cells augmented
      phospholipid production and initiated a genetic program, including elevated
      expression of the genes for the synthesis, elongation, and desaturation of fatty
      acids that supply the phospholipid acyl moieties. Likewise, many of the genes in
      phospholipid biosynthesis were up-regulated, most notably those encoding Lipin1
      and choline phosphotransferase. In contrast, CTP:phosphocholine
      cytidylyltransferase alpha (CCTalpha) protein, a key control point in
      phosphatidylcholine biosynthesis, increased because of stabilization of protein
      turnover rather than transcriptional activation. Furthermore, an elevation in
      cellular diacylglycerol and fatty acid correlated with enhanced allosteric
      activation of CCTalpha by the membrane lipids. This work defines a genetic and
      biochemical program for membrane phospholipid biogenesis that correlates with an
      increase in the phospholipid components of the endoplasmic reticulum and Golgi
      compartments in LPS-stimulated B-cells.

PMID- 17213196
TI  - Heat shock factor 2 (HSF2) contributes to inducible expression of hsp genes
      through interplay with HSF1.
AB  - The heat shock response is a defense reaction activated by proteotoxic damage
      induced by physiological or environmental stress. Cells respond to the
      proteotoxic damage by elevated expression of heat shock proteins (Hsps) that
      function as molecular chaperones and maintain the vital homeostasis of protein
      folds. Heat shock factors (HSFs) are the main transcriptional regulators of the
      stress-induced expression of hsp genes. Mammalian HSF1 was originally identified
      as the transcriptional regulator of the heat shock response, whereas HSF2 has not
      been implicated a role in the stress response. Previously, we and others have
      demonstrated that HSF1 and HSF2 interact through their trimerization domains, but
      the functional consequence of this interaction remained unclear. We have now
      demonstrated on chromatin that both HSF1 and HSF2 were able to bind the hsp70
      promoter not only in response to heat shock but also during hemin-induced
      differentiation of K562 erythroleukemia cells. In both cases an intact HSF1 was
      required in order to reach maximal levels of promoter occupancy, suggesting that
      HSF1 influences the DNA binding activity of HSF2. The functional consequence of
      the HSF1-HSF2 interplay was demonstrated by real-time reverse transcription-PCR
      analyses, which showed that HSF2 was able to modulate the HSF1-mediated
      expression of major hsp genes. Our results reveal, contrary to the predominant
      model, that HSF2 indeed participates in the transcriptional regulation of the
      heat shock response.

PMID- 17213197
TI  - Specificity of the deoxyhypusine hydroxylase-eukaryotic translation initiation
      factor (eIF5A) interaction: identification of amino acid residues of the enzyme
      required for binding of its substrate, deoxyhypusine-containing eIF5A.
AB  - Deoxyhypusine hydroxylase (DOHH) is a novel metalloenzyme that catalyzes the
      final step of the post-translational synthesis of hypusine (Nepsilon-(4-amino-2
      hydroxybutyl)lysine) in the eukaryotic translation initiation factor 5A (eIF5A).
      Hypusine synthesis is unique in that it occurs in only one protein, denoting the
      strict specificity of the modification enzymes toward the substrate protein. The
      specificity of the interaction between eIF5A and DOHH was investigated using
      human eIF5A (eIF5A-1 isoform) and human recombinant DOHH. DOHH displayed a strong
      preference for binding the deoxyhypusine-containing form of eIF5A, over the eIF5A
      precursor or the hypusine-containing eIF5A, indicating a role for the
      deoxyhypusine residue in binding. In addition to the deoxyhypusine residue, a
      large portion of the eIF5A polypeptide (>20-90 amino acids) is required for
      effective modification by DOHH. We have identified the amino acid residues of
      DOHH that are critical for substrate binding by alanine substitution of 36
      conserved amino acid residues. Of these, alanine substitution at Glu57, Glu90,
      Glu208, Glu241, Gly63, or Gly214 caused a severe impairment in eIF5A(Dhp)
      binding, with a complete loss of binding and activity in the E57A and E208A
      mutant enzymes. Only aspartate substitution mutants, E57D or E208D, retained
      partial activity and substrate binding, whereas alanine, glutamine, or asparagine
      mutants did not. These findings support a proposed model of DOHH-eIF5A binding in
      which the amino group(s) of the deoxyhypusine side chain of the substrate is
      primarily anchored by gamma-carboxyl groups of Glu57 and Glu208 at the DOHH
      active site.

PMID- 17213198
TI  - Essential role for caspase-8 in Toll-like receptors and NFkappaB signaling.
AB  - In addition to its pro-apoptotic function in the death receptor pathway, roles
      for caspase-8 in mediating T-cell proliferation, maintaining lymphocyte
      homeostasis, and suppressing immunodeficiency have become evident. Humans with a
      germline point mutation of CASPASE-8 have multiple defects in T cells, B cells,
      and NK cells, most notably attenuated activation and immunodeficiency. By
      generating mice with B-cell-specific inactivation of caspase-8 (bcasp8(-/-)), we
      show that caspase-8 is dispensable for B-cell development, but its loss in B
      cells results in attenuated antibody production upon in vivo viral infection. We
      also report an important role for caspase-8 in maintaining B-cell survival
      following stimulation of the Toll-like receptor (TLR)2, -3, and -4. In response
      to TLR4 stimulation, caspase-8 is recruited to a complex containing IKKalphabeta,
      and its loss resulted in delayed NFkappaB nuclear translocation and impaired
      NFkappaB transcriptional activity. Our study supports dual roles for caspase-8 in
      apoptotic and nonapoptotic functions and demonstrates its requirement for TLR
      signaling and in the regulation of NFkappaB function.

PMID- 17213199
TI  - Lamina-associated polypeptide 2-alpha forms homo-trimers via its C terminus, and
      oligomerization is unaffected by a disease-causing mutation.
AB  - The nucleoplasmic protein, Lamina-associated polypeptide (LAP) 2alpha, is one of
      six alternatively spliced products of the LAP2gene, which share a common N
      terminal region. In contrast to the other isoforms, which also share most of
      their C termini, LAP2alpha has a large unique C-terminal region that contains
      binding sites for chromatin, A-type lamins, and retinoblastoma protein. By
      immunoprecipitation analyses of LAP2alpha complexes from cells expressing
      differently tagged LAP2alpha proteins and fragments, we demonstrate that
      LAP2alpha forms higher order structures containing multiple LAP2alpha molecules
      in vivo and that complex formation is mediated by the C terminus. Solid phase
      binding assays using recombinant and in vitro translated LAP2alpha fragments
      showed direct interactions of LAP2alpha C termini. Cross-linking of LAP2alpha
      complexes and multiangle light scattering of purified LAP2alpha revealed the
      existence of stable homo-trimers in vivo and in vitro. Finally, we show that, in
      contrast to the LAP2alpha-lamin A interaction, its self-association is not
      affected by a disease-linked single point mutation in the LAP2alpha C terminus.

PMID- 17213200
TI  - Interleukin-6 induces keratin expression in intestinal epithelial cells:
      potential role of keratin-8 in interleukin-6-induced barrier function
      alterations.
AB  - Keratin 8 (K8) and keratin-18 (K18) are the major intermediate filament proteins
      in the intestinal epithelia. The regulation and function of keratin in the
      intestinal epithelia is largely unknown. In this study we addressed the role and
      regulation of K8 and K18 expression by interleukin 6 (IL-6). Caco2-BBE cell line
      and IL-6 null mice were used to study the effect of IL-6 on keratin expression.
      Keratin expression was studied by Northern blot, Western blot, and confocal
      microscopy. Paracellular permeability was assessed by apical-to-basal transport
      of a fluorescein isothiocyanate dextran probe (FD-4). K8 was silenced using the
      small interfering RNA approach. IL-6 significantly up-regulated mRNA and protein
      levels of K8 and K18. Confocal microscopy showed a reticular pattern of
      intracellular keratin localized to the subapical region after IL-6 treatment. IL
      6 also induced serine phosphorylation of K8. IL-6 decreased paracellular flux of
      FD-4 compared with vehicle-treated monolayers. K8 silencing abolished the
      decrease in paracellular permeability induced by IL-6. Administration of dextran
      sodium sulfate (DSS) significantly increased intestinal permeability in IL-6-/-
      mice compared with wild type mice given DSS. Collectively, our data demonstrate
      that IL-6 regulates the colonic expression of K8 and K18, and K8/K18 mediates
      barrier protection by IL-6 under conditions where intestinal barrier is
      compromised. Thus, our data uncover a novel function of these abundant
      cytoskeletal proteins, which may have implications in intestinal disorders such
      as inflammatory bowel disease wherein barrier dysfunction underlies the
      inflammatory response.

PMID- 17213201
TI  - Inhibition of mitochondrial respiration as a source of adaphostin-induced
      reactive oxygen species and cytotoxicity.
AB  - Adaphostin is a dihydroquinone derivative that is undergoing extensive
      preclinical testing as a potential anticancer drug. Previous studies have
      suggested that the generation of reactive oxygen species (ROS) plays a critical
      role in the cytotoxicity of this agent. In this study, we investigated the source
      of these ROS. Consistent with the known chemical properties of dihydroquinones,
      adaphostin simultaneously underwent oxidation to the corresponding quinone and
      generated ROS under aqueous conditions. Interestingly, however, this quinone was
      not detected in intact cells. Instead, high performance liquid chromatography
      demonstrated that adaphostin was concentrated by up to 300-fold in cells relative
      to the extracellular medium and that the highest concentration of adaphostin
      (3000-fold over extracellular concentrations) was detected in mitochondria.
      Consistent with a mitochondrial site for adaphostin action, adaphostin-induced
      ROS production was diminished by >75% in MOLT-4 rho(0) cells, which lack
      mitochondrial electron transport, relative to parental MOLT-4 cells. In addition,
      inhibition of oxygen consumption was observed when intact cells were treated with
      adaphostin. Loading of isolated mitochondria to equivalent adaphostin
      concentrations caused inhibition of uncoupled oxygen consumption in mitochondria
      incubated with the complex I substrates pyruvate and malate or the complex II
      substrate succinate. Further analysis demonstrated that adaphostin had no effect
      on pyruvate or succinate dehydrogenase activity. Instead, adaphostin inhibited
      reduced decylubiquinone-induced cytochrome c reduction, identifying complex III
      as the site of inhibition by this agent. Moreover, adaphostin enhanced the
      production of ROS by succinate-charged mitochondria. Collectively, these
      observations demonstrate that mitochondrial respiration rather than direct redox
      cycling of the hydroquinone moiety is a source of adaphostin-induced ROS and
      identify complex III as a potential target for antineoplastic agents.

PMID- 17213202
TI  - RSK2 mediates muscle cell differentiation through regulation of NFAT3.
AB  - RSK2, an ERK downstream kinase, is a novel mediator of skeletal muscle cell
      differentiation through its regulation of NFAT3 activity. We found that the N
      terminal (amino acids (aa) 1-68) and C-terminal (aa 416-674) kinase domains of
      RSK2 directly interacted with nuclear localization signal 1, the Ser/Pro repeat,
      and the polyproline domains (aa 261-365) of NFAT3. Upon A23187 stimulation, RSK2
      induced nuclear localization of NFAT3. RSK2 phosphorylated NFAT3 in vitro
      (Km=3.559 microM), and activation of NFAT3 by RSK2 enhanced the promoter activity
      of NFAT3 downstream target genes in vivo. Furthermore, nuclear accumulation of
      NFAT3 was attenuated markedly in RSK2-/- cells compared with wild-type RSK2+/+
      cells. Notably, RSK2 and NFAT3 induced a significant differentiation of C2C12
      myoblasts to multinucleated myotubes. Multinucleated myotube differentiation was
      inhibited by small interfering RNA against RSK2, ERK1/2, or NFAT3. These results
      demonstrate that RSK2 is an important kinase for NFAT3 in mediating myotube
      differentiation.

PMID- 17213203
TI  - The hop cassette of the PAC1 receptor confers coupling to Ca2+ elevation required
      for pituitary adenylate cyclase-activating polypeptide-evoked neurosecretion.
AB  - We have identified the single PAC1 receptor variant responsible for Ca2+
      mobilization from intracellular stores and influx through voltage-gated Ca2+
      channels in bovine chromaffin cells and the domain of this receptor variant that
      confers coupling to [Ca2+]i elevation. This receptor (bPAC1hop) contains a 28
      amino acid "hop" insertion in the third intracellular loop, with a full-length
      171-amino acid N terminus. Expression of the bPAC1hop receptor in NG108-15 cells,
      which lack endogenous PAC1 receptors, reconstituted high affinity PACAP binding
      and PACAP-dependent elevation of both cAMP and intracellular Ca2+ concentrations
      ([Ca2+]i). Removal of the hop domain and expression of this receptor (bPAC1null)
      in NG108-15 cells reconstituted high affinity PACAP binding and PACAP-dependent
      cAMP generation but without a corresponding [Ca2+]i elevation. PC12-G cells
      express sufficient levels of PAC1 receptors to provide PACAP-saturable coupling
      to adenylate cyclase and to drive PACAP-dependent differentiation but do not
      express PAC1 receptors at levels found in postmitotic neuronal and endocrine
      cells and do not support PACAP-mediated neurosecretion. Expression of bPAC1hop,
      but not bPAC1(null), at levels comparable with those of bPAC1hop in bovine
      chromaffin cells resulted in acquisition by PC12-G cells of PACAP-dependent
      [Ca2+]i increase and extracellular Ca2+ influx. In addition, PC12-G cells
      expressing bPAC1hop acquired the ability to release [3H]norepinephrine in a Ca2+
      influx-dependent manner in response to PACAP. Expression of PACAP receptors in
      neuroendocrine rather than nonneuroendocrine cells reveals key differences
      between PAC1hop and PAC1null coupling, indicating an important and previously
      unrecognized role of the hop cassette in PAC1-mediated Ca2+ signaling in
      neuroendocrine cells.

PMID- 17213204
TI  - CD2AP/CIN85 balance determines receptor tyrosine kinase signaling response in
      podocytes.
AB  - Defects in podocyte signaling are the basis of many inherited glomerular diseases
      leading to glomerulosclerosis. CD2-associated protein (CD2AP) is highly expressed
      in podocytes and is considered to play an important role in the maintenance of
      the glomerular slit diaphragm. Mice deficient for CD2AP (CD2AP(-/-)) appear
      normal at birth but develop a rapid onset nephrotic syndrome at 3 weeks of age.
      We demonstrate that impaired intracellular signaling with subsequent podocyte
      damage is the reason for this delayed podocyte injury in CD2AP(-/-) mice. We
      document that CD2AP deficiency in podocytes leads to diminished signal initiation
      and termination of signaling pathways mediated by receptor tyrosine kinases
      (RTKs). In addition, we demonstrate that CIN85, a paralog of CD2AP, is involved
      in termination of RTK signaling in podocytes. CIN85 protein expression is
      increased in CD2AP(-/-) podocytes in vitro. Stimulation of CD2AP(-/-) podocytes
      with various growth factors, including insulin-like growth factor 1, vascular
      endothelial growth factor, and fibroblast growth factor, resulted in a
      significantly decreased phosphatidylinositol 3-kinase/AKT and ERK signaling
      response. Moreover, increased CIN85 protein is detectable in podocytes in
      diseased CD2AP(-/-) mice, leading to decreased base-line activation of ERK and
      decreased phosphorylation after growth factor stimulation in vivo. Because
      repression of CIN85 protein leads to a restored RTK signaling response, our
      results support an important role of CD2AP/CIN85 protein balance in the normal
      signaling response of podocytes.

PMID- 17213205
TI  - Knockdown of aminopeptidase-N from Helicoverpa armigera larvae and in transfected
      Sf21 cells by RNA interference reveals its functional interaction with Bacillus
      thuringiensis insecticidal protein Cry1Ac.
AB  - Aminopeptidase-N (APN) and cadherin proteins located at the midgut epithelium of
      Helicoverpa armigera have been implicated as receptors for the Cry1A subfamily of
      insecticidal proteins of Bacillus thuringiensis. Ligand blot analysis with
      heterologously expressed and purified H. armigera Bt receptor with three closely
      related Cry1A proteins tentatively identified HaAPN1 as an interacting ligand.
      However, to date there is no direct evidence of APN being a functional receptor
      to Cry1Ac in H. armigera. Sf21 insect cells expressing HaAPN1 displayed aberrant
      cell morphology upon overlaying with Cry1Ac protein. Down-regulating expression
      of HaAPN1 by RNA interference using double-stranded RNA correlated with a
      corresponding reduction in the sensitivity of HaAPN1-expressing cells to Cry1Ac
      protein. This clearly establishes that insect cells expressing the receptor
      recruit sensitivity to the insecticidal protein Cry1Ac, and their susceptibility
      is directly dependent on the amount of HaAPN1 protein expressed. Most
      importantly, silencing of HaAPN1 in H. armigera in vivo by RNA interference
      resulted in reduced transcript levels and a corresponding decrease in the
      susceptibility of larvae to Cry1Ac. BIAcore analysis of HaAPN1/Cry1Ac interaction
      further established HaAPN1 as a ligand for Cry1Ac. This is the first functional
      demonstration of insect aminopeptidase-N of H. armigera being a receptor of
      Cry1Ac protein of B. thuringiensis.

PMID- 17213206
TI  - Dramatic accumulation of triglycerides and precipitation of cardiac hemodynamic
      dysfunction during brief caloric restriction in transgenic myocardium expressing
      human calcium-independent phospholipase A2gamma.
AB  - Previously, we identified calcium-independent phospholipase A2gamma (iPLA2gamma)
      with multiple translation initiation sites and dual mitochondrial and peroxisomal
      localization motifs. To determine the role of iPLA2gamma in integrating lipid and
      energy metabolism, we generated transgenic mice containing the alpha-myosin heavy
      chain promoter (alphaMHC) placed proximally to the human iPLA2gamma coding
      sequence that resulted in cardiac myocyte-restricted expression of iPLA2gamma
      (TGiPLA2gamma). TGiPLA2gamma mice possessed multiple phenotypes including: 1) a
      dramatic approximately 35% reduction in myocardial phospholipid mass in both the
      fed and mildly fasted states; 2) a marked accumulation of triglycerides during
      brief caloric restriction that represented 50% of total myocardial lipid mass;
      and 3) acute fasting-induced hemodynamic dysfunction. Biochemical
      characterization of the TGiPLA2gamma protein expressed in cardiac myocytes
      demonstrated over 25 distinct isoforms by two-dimensional SDS-PAGE Western
      analysis. Immunohistochemistry identified iPLA2gamma in the peroxisomal and
      mitochondrial compartments in both wild type and transgenic myocardium. Electron
      microscopy revealed the presence of loosely packed and disorganized mitochondrial
      cristae in TGiPLA2gamma mice that were accompanied by defects in mitochondrial
      function. Moreover, markedly elevated levels of 1-hydroxyl-2-arachidonoyl-sn
      glycero-3-phosphocholine and 1-hydroxyl-2-docosahexaenoyl-sn-glycero-3
      phosphocholine were prominent in the TGiPLA2gamma myocardium identifying the
      production of signaling metabolites by this enzyme in vivo. Collectively, these
      results identified the participation of iPLA2gamma in the remarkable lipid
      plasticity of myocardium, its role in generating signaling metabolites, and its
      prominent effects in modulating energy storage and utilization in myocardium in
      different metabolic contexts.

PMID- 17213207
TI  - Commentary: The relationship between parity and overweight--a life course
      perspective.

PMID- 17213208
TI  - Teenage pregnancy and adverse birth outcomes: a large population based
      retrospective cohort study.
AB  - BACKGROUND: Whether the association between teenage pregnancy and adverse birth
      outcomes could be explained by deleterious social environment, inadequate
      prenatal care, or biological immaturity remains controversial. The objective of
      this study was to determine whether teenage pregnancy is associated with
      increased adverse birth outcomes independent of known confounding factors.
      METHODS: We carried out a retrospective cohort study of 3,886,364 nulliparous
      pregnant women <25 years of age with a live singleton birth during 1995 and 2000
      in the United States. RESULTS: All teenage groups were associated with increased
      risks for pre-term delivery, low birth weight and neonatal mortality. Infants
      born to teenage mothers aged 17 or younger had a higher risk for low Apgar score
      at 5 min. Further adjustment for weight gain during pregnancy did not change the
      observed association. Restricting the analysis to white married mothers with age
      appropriate education level, adequate prenatal care, without smoking and alcohol
      use during pregnancy yielded similar results. CONCLUSIONS: Teenage pregnancy
      increases the risk of adverse birth outcomes that is independent of important
      known confounders. This finding challenges the accepted opinion that adverse
      birth outcome associated with teenage pregnancy is attributable to low
      socioeconomic status, inadequate prenatal care and inadequate weight gain during
      pregnancy.

PMID- 17213209
TI  - Differential impacts of health care in Australia: trend analysis of socioeconomic
      inequalities in avoidable mortality.
AB  - BACKGROUND: Recent avoidable mortality trends in Australia suggest that health
      care has made a substantial contribution to reducing mortality. This study
      investigates if the benefits of health care have been distributed equally by
      comparing declines in avoidable with non-avoidable mortality over time by
      socioeconomic status (SES). METHODS: We calculated avoidable and non-avoidable
      mortality rates in Australia by small areas for 1986, 1991, 1997 and 2002. We
      performed pooled cross-sectional trend analysis of indirectly standardized
      mortality rates by SES and year, modelling using Poisson regression with over
      dispersion. Socioeconomic inequalities were quantified using the relative (RII)
      and slope (SII) index of inequality. RESULTS: The annual percentage decline in
      avoidable mortality at the higher end of the socioeconomic continuum (5.0%; 95%
      CI: 4.7-5.4%) was larger than at the lower end (3.5%; 3.2-3.8%), with increasing
      relative inequality between 1986 (RII = 1.54; 1.46-1.63) and 2002 (RII = 2.00;
      1.95-2.06), greater than that in non-avoidable mortality (P = 0.036). In absolute
      terms, avoidable deaths fell annually by 7.4 (6.9-7.8) and 8.4 (7.9-8.9) deaths
      per 100 000 at the higher and lower end of the spectrum, respectively, with
      absolute inequality decreasing between 1986 (SII = 97.8; 87.6-107.9) and 2002
      (SII = 81.5; 74.6-88.5). CONCLUSIONS: Health care has contributed to decreasing
      the absolute SES mortality gap. However, advantaged people have obtained a
      disproportionate benefit of health care, contributing to widening relative health
      inequalities. A universal heath care system does not guarantee equality in health
      care-related outcomes.

PMID- 17213212
TI  - Dietary diversity in Khon Kaen, Thailand, 1988 2006.

PMID- 17213213
TI  - Commentary: Why are South Asians susceptible to central obesity?--the El Nino
      hypothesis.

PMID- 17213214
TI  - Cohort profile: the North American AIDS Cohort Collaboration on Research and
      Design (NA-ACCORD).

PMID- 17213215
TI  - Dopaminergic therapy promotes lateralized motor activity in the subthalamic area
      in Parkinson's disease.
AB  - Treatment of patients with Parkinson's disease with levodopa has profound effects
      on both movement and the pattern of movement-related reactivity in the
      subthalamic nucleus (STN), as reflected in the local field potential (LFP). The
      most striking change is the promotion of reactivity in the gamma frequency band,
      but it remains unclear whether the latter is itself a pathological feature,
      possibly associated with levodopa induced dyskinesias, or is primarily
      physiological. Gamma band reactivity in the cerebral cortex of humans without
      Parkinson's disease occurs contralateral to movement, so we posited that
      lateralization of subcortical gamma reactivity should occur following levodopa if
      the latter restores a more physiological pattern in patients with Parkinson's
      disease. Accordingly, we studied movement-related changes in STN LFP activity in
      11 Parkinson's disease patients (age 59 +/- 2.7 years, three females) while they
      performed ipsi- and contralateral self-paced joystick movements ON and OFF
      levodopa. A bilaterally symmetrical gamma band power increase occurred around
      movement onset in the OFF state. Following levodopa this feature became
      significantly more pronounced in the subthalamic region contralateral to
      movement. The physiological nature of this asymmetric pattern of gamma reactivity
      was confirmed in the STN of two tremor patients without Parkinson's disease.
      Although levodopa treatment in the Parkinson's disease patients did not lead to
      lateralization of power suppression at lower frequencies (8-30 Hz), it did
      increase the degree of power suppression. These findings suggest that
      dopaminergic therapy restores a more physiological pattern of reactivity in the
      STN of patients with Parkinson's disease.

PMID- 17213216
TI  - State-of-the-art dosimetric methods for internal and external exposures:
      conclusions of a EURADOS action.
AB  - In radiation protection dosimetry the quantity of interest is the effective dose
      (E); the dose limit to an adult worker applies to the sum of the relevant doses
      from external exposures and the relevant committed effective doses from intakes
      of radionuclides, during the same period of time. A EURADOS study was carried out
      to investigate how the results from personal dosemeters for external radiation,
      from workplace monitoring and from monitoring of internal exposures can be
      combined into a consistent system of individual monitoring. The integration of
      dosimetric methods and data for external and internal radiation require the
      complete characterisation of the occupational exposure present at the workplace,
      and the availability of adequate equipment and tools for the assessment of
      effective dose. To evaluate the capability of services to accomplish this
      approach, a European Dosimetry Network has been established among 28 European
      countries through the respective contact-persons and their dosimetric facilities
      which collaborated with EURADOS providing relevant data about performance and
      legal aspects. The information collected was presented as a monograph in
      Radiation Protection Dosimetry in 2004. The more relevant conclusions of this
      study are presented here.

PMID- 17213217
TI  - Dependence of nanodosimetric spectra on the sensitive volume length and ion drift
      in an ion-counting nanodosemeter.
AB  - Nanodosimetric spectra, measured in a well-defined ionisation sensitive volume of
      an ion-counting gaseous nanodosemeter, may have a valuable predictive value of
      radiation damage to DNA. In such devices, the distributions of radiation-induced
      ions are measured after their drift in gas. The sensitive-volume size,
      corresponding to a DNA segment length, can be tuned by selecting an appropriate
      time window for ion counting; the method's accuracy depends on the velocity
      distribution of the drifting ions. The results of ion-drift measurements in an
      ion-counting nanodosemeter were used for the precise calculation of its sensitive
      volume length. Monte Carlo simulations of nanodosimetric spectra, performed with
      the obtained data, are in good agreement with experimental data. The method's
      limitations, arising from the spread of drift velocities, are discussed.

PMID- 17213218
TI  - Compliance of electronic personal neutron dosemeters with the new International
      Standard IEC 61526.
AB  - The recommendations and test requests for the dose equivalent response of
      personal neutron dosemeters formulated by the new International Standard IEC
      61526 are summarised. In particular, IEC 61526 allows the use of broad fields if
      dosemeters do not fulfil the hard requirements using monoenergetic neutrons. Some
      broad fields which can work as a replacement field using ISO sources (252Cf,
      252Cf (D2O mod.), 241Am-Be) and simulated workplace fields (CANEL and SIGMA) are
      described. This work shows the results of recent measurements of the personal
      dose equivalent response for the dosemeters Thermo Electron EPD-N2, Aloka PDM-313
      and the prototype dosemeter PTB DOS-2002, and discusses their compliance with
      respect to the new IEC 61526 standard.

PMID- 17213219
TI  - Killing of target cells due to radon progeny in the human lung.
AB  - The dose conversion coefficient (DCC) is used to assess the risk due to inhaled
      radon progeny in the human lung. The present work uses the microdosimetric
      approach and determines the linear energy transfer in the target cell nuclei.
      Killing of target cells was also taken into account through an effect-specific
      track length model. To focus on the relevant part of the absorbed dose in the
      cell nuclei, the absorbed dose, which causes cell-killing is discarded in the
      final calculations of the DCC. Following this approach, the calculated DCC has
      become 3.4 mSv WLM(-1) which is very close to the epidemiologically derived value
      of approximately 4 mSv WLM(-1).

PMID- 17213220
TI  - Radiation-induced micronucleus frequencies in female peripheral blood lymphocytes
      collected during the first and second half of the menstrual cycle.
AB  - Biological dosimetry relies on the assessment of dose in peripheral blood
      lymphocytes (PBL) of a victim. Variability in the individual radiosensitivity of
      PBL has an impact on the precision of dose estimate and radiation-induced
      micronuclei show a strong individual variability. A factor which can influence
      the radiosensitivity of PBL is the hormonal status of female donors, which shows
      a regular pattern during the menstrual cycle. The aim of the present
      investigation was to verify whether the position within the menstrual cycle has
      an impact on the level of micronuclei in PBL. Blood was collected from 19 donors
      during the first and second half of the menstrual cycle and exposed to 2 Gy.
      Although statistically significant differences between the MN frequencies in PBL
      collected during the different time points were observed in the case of some
      donors, no reproducible trend that could find application in biological dosimetry
      could be detected.

PMID- 17213221
TI  - Nanodosemeters based on gel scintillators.
AB  - The feasibility of a nanodosemeter based on a liquid scintillator cocktail of
      four components (ethoxylated nonylphenol, pseudocumene, water and a lipophilic
      mixture) is studied. The dosemeter can work in distinct gel phases, for which the
      radioactive substance can be confined inside aqueous nanoscale structures of
      different size. For water volumes ranging 0-15%, it results in a gel with
      micelles of 4 nm radius. For water volumes ranging 30-50%, the resulting liquid
      crystal gel contains nanostructures of approximately 20 nm radius. The low-energy
      electron emission arising from the decay of (3)H and (55)Fe is counted in a
      commercial liquid-scintillation counting spectrometer for both homogeneous and
      gel samples. The counting efficiency gap between the two phases is used to
      compute the average energy deposited inside the micelle.

PMID- 17213222
TI  - Detailed analysis of the response of different cell lines to carbon irradiation.
AB  - Published survival data for Chinese hamster ovarian cells CHO-K1 and their
      radiosensitive mutant xrs5 after irradiation by carbon ions of energies from 2.4
      to 266.4 MeV u(-1) have been analysed using the probabilistic two-stage
      radiobiological model, which enables to represent the interplay of damage
      induction and repair processes. The results give support for the hypothesis that
      the differences in radiation sensitivity of diverse cell lines are given
      primarily by their different repair capabilities, and indicate the need for
      explicitly representing the outcome of repair processes in radiobiological models
      and treatment-planning approaches in radiotherapy.

PMID- 17213223
TI  - The comparison of calculated and experimental microdosimetric distributions for
      carbon ions.
AB  - The aim of this work is to present microdosimetric characteristics of 400 MeV
      amu(-1) and 500 MeV amu(-1) carbon ions obtained by theoretical calculations and
      to analyse them with respect to experimental data obtained by tissue-equivalent
      proportional counter in a scope of project ICCHIBAN and by etched track detector
      CR 39 Page irradiated by LHE nuclotron at JINR, Dubna, Russia. Track structures
      provided by Monte Carlo code TRIOL are used as an input data for calculations of
      energy distributions. The calculations of frequency f(y) and dose d(y)
      distributions are performed using own developed programs.

PMID- 17213224
TI  - Radio frequency exposure in mobile phone users: implications for exposure
      assessment in epidemiological studies.
AB  - The majority of epidemiological studies investigating correlations between long
      term low-level radiofrequency (RF) exposure from mobile phones and health
      endpoints have followed a case-control design, requiring reconstruction of
      individual RF exposure. To date, these have employed 'time of use' as an exposure
      surrogate from questionnaire information or billing records. The present study
      demonstrates such an approach may not account for variability in mobile phone
      transmit power, which can be roughly correlated with RF exposure. This
      variability exists (a) during a single call, (b) between separate calls, (c)
      between averaged values from individuals within a local study group and (d)
      between average values from groups in different geographical locations. The
      present data also suggest an age-related influence on talk time, as well as
      significant inaccuracy (45-60%) in recalling 'time of use'. Evolving technology
      and changing use behaviours may add additional complexities. Collectively, these
      data suggest efforts to identify dose response and statistical correlations
      between mobile phone use and subtle health endpoints may be significantly
      challenged.

PMID- 17213225
TI  - Lumping, splitting and mapping: assessing linkage in different ethnic groups for
      albuminuria and glomerular filtration rate in the HyperGen study.

PMID- 17213226
TI  - In memoriam 'analgesic nephropathy' (circa 1972-2006).

PMID- 17213227
TI  - Markers of oxidative stress in the skeletal muscle of patients on haemodialysis.
AB  - BACKGROUND: Increased oxidative stress may play a role in morbidity and mortality
      of patients with renal failure. Most studies have examined serum markers of
      oxidation, but it is unclear whether oxidative stress is involved in skeletal
      muscle atrophy. METHODS: This study examined markers of oxidative stress in the
      skeletal muscle of 10 haemodialysed patients and 10 control subjects. Biopsies
      from the quadriceps femoris were analysed for reduced and oxidized glutathione,
      protein thiols, malonaldehyde and heat shock proteins (HSP27, HSP60 and HSP70),
      superoxide dismutase and catalase activities. A novel microdialysis procedure was
      used to examine hydroxyl radical activity in the interstitial fluid of the
      tibialis anterior. RESULTS: Patients had muscle atrophy with a reduced diameter
      of both type I and II fibres (by 15 and 20%, respectively). Muscle
      microdialysates contained 2,3- and 2,5-dihydroxybenzoates formed from salicylate
      indicating hydroxyl radical activity, with no differences between patients and
      control subjects. Muscle protein thiol and oxidized glutathione contents were
      unchanged in patients, but malonaldehyde content was reduced. In contrast, total
      muscle glutathione and heat shock protein contents were increased. Muscle
      superoxide dismutase activity was unchanged, but catalase activity was reduced in
      patients. CONCLUSIONS: The muscle of patients undergoing haemodialysis undergoes
      some adaptive responses in total glutathione content, heat shock protein content
      and catalase activity that are potentially related to chronic oxidative stress.
      However, there is no evidence of gross oxidation, nor any clear relationship
      between oxidative stress and muscle fibre atrophy, arguing against a direct role
      of oxidants in the degenerative processes.

PMID- 17213228
TI  - Lovastatin insensitive 1, a Novel pentatricopeptide repeat protein, is a
      potential regulatory factor of isoprenoid biosynthesis in Arabidopsis.
AB  - Higher plants have two metabolic pathways for isoprenoid biosynthesis: the
      cytosolic mevalonate (MVA) pathway and the plastidal non-mevalonate (MEP)
      pathway. Despite the compartmentalization of these two pathways, metabolic flow
      occurs between them. However, little is known about the mechanisms that regulate
      the two pathways and the metabolic cross-talk. To identify such regulatory
      mechanisms, we isolated and characterized the Arabidopsis T-DNA insertion mutant
      lovastatin insensitive 1 (loi1), which is resistant to lovastatin and clomazone,
      inhibitors of the MVA and MEP pathways, respectively. The accumulation of the
      major products of these pathways, i.e. sterols and chlorophyll, was less affected
      by lovastatin and clomazone, respectively, in loi1 than in the wild type.
      Furthermore, the 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity
      analysis showed higher activity of HMGR in loi1-1 treated with lovastatin than
      that in the WT. We consider that the lovastatin-resistant phenotype of loi1-1 was
      derived from this post-transcriptional up-regulation of HMGR. The LOI1 gene
      encodes a novel pentatricopeptide repeat (PPR) protein. PPR proteins are thought
      to regulate the expression of genes encoded in organelle genomes by post
      transcriptional regulation in mitochondria or plastids. Our results demonstrate
      that LOI1 is predicted to localize in mitochondria and has the ability to bind
      single-stranded nucleic acids. Our investigation revealed that the post
      transcriptional regulation of mitochondrial RNA may be involved in isoprenoid
      biosynthesis in both the MVA and MEP pathways.

PMID- 17213229
TI  - Inflammatory, haemostatic, and rheological markers for incident peripheral
      arterial disease: Edinburgh Artery Study.
AB  - AIMS: Recently, markers of inflammation, haemostasis, and blood rheology have
      received much attention as risk factors for coronary heart disease and stroke.
      However, their role in peripheral arterial disease (PAD) is not well established
      and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6),
      have not been examined before in prospective epidemiological studies. METHODS AND
      RESULTS: In the Edinburgh Artery Study, we studied the development of PAD in the
      general population and evaluated 17 potential blood markers as predictors of
      incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were
      recruited. After 17 years, 208 subjects had developed symptomatic PAD. In
      analysis adjusted for cardiovascular risk factors and baseline cardiovascular
      disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and
      haematocrit [hazard ratio (95% CI) corresponding to an increase equal to the
      inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22
      (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these
      markers provided very little prognostic information for incident PAD to that
      obtained by cardiovascular risk factors and the ankle brachial index. Other
      markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue
      plasminogen activator antigen, and plasma and blood viscosities showed weak
      associations, which were considerably attenuated when CVD risk factors were
      accounted for. CONCLUSIONS: Our prospective data showed that several
      inflammatory, haemostatic, and rheological markers are associated with incident
      PAD; however, their clinical utility is likely to be limited. Future research is
      necessary to validate the importance of these biomarkers explicitly on PAD and to
      address the causality of the reported associations.

PMID- 17213230
TI  - Addition of milk prevents vascular protective effects of tea.
AB  - AIMS: Experimental and clinical studies indicate that tea exerts protection
      against cardiovascular diseases. However, a question of much debate is whether
      addition of milk modifies the biological activities of tea. We studied the
      vascular effects of tea, with or without milk, in humans and elucidated the
      impact of individual milk proteins in cell culture experiments, with isolated rat
      aortic rings and by HPLC analysis. METHODS AND RESULTS: A total of 16 healthy
      female volunteers consumed either 500 mL of freshly brewed black tea, black tea
      with 10% skimmed milk, or boiled water as control. Flow-mediated dilation (FMD)
      was measured by high-resolution vascular ultrasound before and 2 h after
      consumption. Black tea significantly improved FMD in humans compared with water,
      whereas addition of milk completely blunted the effects of tea. To support these
      findings, similar experiments were performed in isolated rat aortic rings and
      endothelial cells. Tea induced vasorelaxation in rat aortic rings and increased
      the activity of endothelial nitric oxide synthase by phosphorylation of the
      enzyme in endothelial cells. All effects were completely inhibited by the
      addition of milk to tea. Of the various kinds of milk proteins, the caseins
      accounted for these inhibiting effects of milk, probably by formation of
      complexes with tea catechins. CONCLUSION: Milk counteracts the favourable health
      effects of tea on vascular function. This finding indicates the need for
      particular awareness in the interpretation and design of studies comprising
      nutritional flavonoids.

PMID- 17213231
TI  - Reduced perlecan in mice results in chondrodysplasia resembling Schwartz-Jampel
      syndrome.
AB  - Perlecan knock-in mice were developed to model Schwartz-Jampel syndrome (SJS), a
      skeletal disease resulting from decreased perlecan. Two mouse strains were
      generated: those carrying a C-to-Y mutation at residue 1532 and the neomycin
      cassette (C1532Yneo) and those harboring the mutation alone (C1532Y).
      Immunostaining, biochemistry, size measurements, skeletal studies and histology
      revealed Hspg2 transcriptional changes in C1532Yneo mice, leading to reduced
      perlecan secretion and a skeletal disease phenotype characteristic of SJS
      patients. Skeletal disease features include smaller size, impaired
      mineralization, misshapen bones, flat face and joint dysplasias reminiscent of
      osteoarthritis and osteonecrosis. Moreover, C1532Yneo mice displayed transient
      expansion of hypertrophic cartilage in the growth plate concomitant with radial
      trabecular bone orientation. In contrast, C1532Y mice, harboring only the
      mutation associated with SJS, displayed a mild phenotype, inconsistent with SJS.
      These studies question the C1532Y mutation as the sole causative factor of SJS in
      the human family harboring this alteration and imply that transcriptional changes
      leading to perlecan reduction may represent the disease mechanism for SJS.

PMID- 17213232
TI  - Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to
      atherosclerosis: a pathological study of 1503 consecutive autopsy cases.
AB  - Atherosclerosis is a chronic inflammatory disease in the intima of the arterial
      wall, where cytokines play a crucial role in the pathogenesis of this disease.
      However, the question of whether or not genetic variations in the cytokine genes
      could influence the development of atherosclerosis has been poorly investigated.
      We investigated the relationship of nine common single-nucleotide polymorphisms
      (SNPs) in tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-10,
      IL-4 and transforming growth factor (TGF)-beta1 with the atherosclerotic severity
      in 10 different arteries based on 1503 consecutive autopsies of elderly Japanese
      subjects registered in the Japanese SNPs for geriatric research (JG-SNP) study.
      The -1031C allele of TNF-alpha was a significant protective factor for
      atherogenesis in the carotid, femoral and intracranial arteries [odds ratio (OR):
      0.72, 0.73 and 0.70, respectively]. The -511T of IL-1beta and the +29T of TGF
      beta1 were significant risk factors for atherogenesis in the subclavian and
      intracranial arteries (OR: 1.35 and 1.48, respectively). In contrast,
      conventional risk factors for atherogenesis, such as hypertension and diabetes
      mellitus, conferred independent risks for almost all arteries. Functional SNPs in
      TNF-alpha, IL-1beta and TGF-beta1 genes play a role in atherogenesis, although
      their influences are less pronounced than those of conventional risk factors and
      appear to be limited to specific arteries in the Japanese elderly.

PMID- 17213233
TI  - Dysregulation of C/EBPalpha by mutant Huntingtin causes the urea cycle deficiency
      in Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disease
      caused by a CAG trinucleotide expansion in the Huntingtin (Htt) gene. Using two
      mouse models of HD, we demonstrate that the urea cycle deficiency characterized
      by hyperammonemia, high blood citrulline and suppression of urea cycle enzymes is
      a prominent feature of HD. The resultant ammonia toxicity might exacerbate the
      neurological deficits of HD. Suppression of C/EBPalpha, a crucial transcription
      factor for the transcription of urea cycle enzymes, appears to mediate the urea
      cycle deficiency in HD. We found that in the presence of mutant Htt, C/EBPalpha
      loses its ability to interact with an important cofactor (CREB-binding protein).
      Moreover, mutant Htt recruited C/EBPalpha into aggregates, as well as suppressed
      expression of the C/EBPalpha gene. Consumption of protein-restricted diets not
      only led to the restoration of C/EBPalpha's activity, and repair of the urea
      cycle deficiency and hyperammonemia, but also ameliorated the formation of Htt
      aggregates, the motor deterioration, the suppression of striatal brain-derived
      neurotrophic factor and the normalization of three protein chaperones (Hsp27,
      Hsp70 and Hsp90). Treatments aimed at repairing the urea cycle deficiency may
      provide a new strategy for dealing with HD.

PMID- 17213234
TI  - Ethnic segregation in Kosovo's post-war health care system.
AB  - BACKGROUND: Seven years after the end of war in Kosovo, Final Status Negotiations
      have begun to determine the long-term political future of the province. This
      article provides an overview of the present situation regarding ethnic groups and
      their relations in Kosovo's health care system that might be helpful in preparing
      for the array of potential ramifications and repercussions that could arise at
      the conclusion of the negotiations. METHODS: A review of the literature
      (including grey) was performed, and 16 interviews and two focus groups with key
      informants were conducted in Kosovo during October and November 2004. In
      addition, six informal discussions were held in-person or by telephone in London.
      Information collected in 2004 was re-confirmed and partially updated in October
      and November 2005, when three additional interviews were conducted in Kosovo.
      RESULTS: Ongoing ethnic tensions in Kosovo, mainly between the Albanian and Serb
      populations, perpetuate a rigidly segregated health care system. Some other
      minority communities, such as the Roma, Ashkali and Egyptians, are afflicted by
      the double burden of getting caught up in the middle of these ethnic disputes and
      at the same time suffering from poverty and discrimination. CONCLUSION: While
      efforts have been put forward to promote peace-building within Kosovo's post-war
      health sector, very little progress has been achieved in fostering ethnic
      integration, reconciliation, cooperation or even co-existence. This failure
      reflects Kosovo's broader unresolved inter-ethnic problems. Final Status
      Negotiations are one of the last opportunities for the international community to
      address the problems of ethnic segregation in the province.

PMID- 17213235
TI  - Introducing Health Impact Assessment: an analysis of political and administrative
      intersectoral working methods.
AB  - BACKGROUND: Intersectoral Action for Health (IAH) and its Health Impact
      Assessment (HIA) tool are built on collaboration between actors and sectors,
      requiring multidimensional and horizontal way of working. The study aims to
      analyse the enablers and barriers when such a new way of working and tool have
      been initiated to replace a traditional, vertical operation at the local level in
      Slovakia-a country in transition-in 2004. METHODS: Up to date, there are few
      studies that have analysed intersectoral initiatives in relation to politics. In
      this study the conceptual framework of Kingdon has been used by which the actual
      problems, the governmental actions (or non-actions) (politics) and the
      understanding, implementation and evaluation of the initiative (policy) could be
      analysed. All actors involved, civil servants, politicians, representatives of
      the local public health institute and researchers, were interviewed and made to
      answer a questionnaire. RESULTS: The results showed that there were a number of
      factors behind the initiation of HIA, which either delayed or accelerated the
      process. The problems identified were e.g. the prevailing traditional health care
      focus and the deteriorating health status of the population. There was a lack of
      multi-intersectoral knowledge, co-operation and function between sectors and
      actors. Enablers on the other hand were the membership of international
      organizations which called for new solutions, and the strong political commitment
      and belief that intersectorality would have a positive effect on health.
      CONCLUSION: The actors on the local level would have the capacity to work
      intersectorally to bring about policy change if HIA was to be more
      supported/institutionalized.

PMID- 17213236
TI  - The effect of exercise on outcomes for older acute medical inpatients compared
      with control or alternative treatments: a systematic review of randomized
      controlled trials.
AB  - OBJECTIVE: To determine the effect of exercise interventions for acutely
      hospitalized older medical patients on functional status and hospital outcomes.
      DATA SOURCES: MEDLINE, CINAHL, EMBASE, Cochrane Database of Systematic Reviews,
      Cochrane Central Register of Controlled Trials, PEDro, Current Contents and
      Sports Discus were searched until February 2006. Additional studies were
      identified through reference and citation tracking and contacting authors of
      eligible trials. REVIEW METHODS: Eligible studies were prospective randomized or
      pseudor and omized controlled trials comparing exercise for medical inpatients to
      alternate or no treatment controls. Of 3138 potentially relevant articles
      screened by two independent reviewers, seven randomized controlled trials and two
      pseudorandomized controlled trials were included. Two independent reviewers
      extracted data relating to patient and hospital outcomes and assessed the method
      quality. RESULTS: Pooled analysis of multidisciplinary interventions that
      included exercise indicated a significant increase in the proportion of patients
      discharged to home at hospital discharge (relative risk 1.08; 95% confidence
      interval (CI) 1.03 -1.14) and a small but important reduction in acute hospital
      length of stay (weighted mean difference - / 1.08 days; 95% CI - / 1.93 to - /
      0.22) and total hospital costs (weighted mean difference - / 280 US dollars; 95%
      CI - / 493 dollars to - / 65 dollars) compared with usual care. Pooled analysis
      of exercise intervention trials found no effect on the proportion of patients
      discharged to home or acute hospital length of stay. The effect of exercise on
      functional outcome measures is unclear. There was no influence of exercise
      intervention on adverse events. CONCLUSIONS: Multidisciplinary intervention that
      includes exercise improves patient and hospital outcomes for acutely hospitalized
      older medical patients.

PMID- 17213237
TI  - Repetitive locomotor training and physiotherapy improve walking and basic
      activities of daily living after stroke: a single-blind, randomized multicentre
      trial (DEutsche GAngtrainerStudie, DEGAS).
AB  - OBJECTIVE: To evaluate the effect of repetitive locomotor training on an
      electromechanical gait trainer plus physiotherapy in subacute stroke patients.
      DESIGN: Randomized controlled trial. SETTING: Four German neurological
      rehabilitation centres. SUBJECTS: One hundred and fifty-five non-ambulatory
      patients (first-time stroke <60 days). INTERVENTION: Group A received 20 min
      locomotor training and 25 min physiotherapy; group B had 45 min physiotherapy
      every week day for four weeks. MAIN OUTCOME MEASURES: Primary variables were gait
      ability (Functional Ambulation Category, 0-5) and the Barthel Index (0-100),
      blindly assessed at study onset, end, and six months later for follow-up.
      Responders to the therapy had to become ambulatory (Functional Ambulation
      Category 4 or 5) or reach a Barthel Index of > or = 75. Secondary variables were
      walking velocity, endurance, mobility and leg power. RESULTS: The intention-to
      treat analysis revealed that significantly greater number of patients in group A
      could walk independently: 41 of 77 versus 17 of 78 in group B (P B < 0.0001) at
      treatment end. Also, significantly more group A patients had reached a Barthel
      Index > or = 75: 44 of 77 versus 21 of 78 (P B < 0.0001). At six-month follow-up,
      the superior gait ability in group A persisted (54 of 77 versus 28 of 78, P B <
      0.0001), while the Barthel Index responder rate did not differ. For all secondary
      variables, group A patients had improved significantly more (P B < 0.0001) during
      the treatment period, but not during follow-up. CONCLUSIONS: Intensive locomotor
      training plus physiotherapy resulted in a significantly better gait ability and
      daily living competence in subacute stroke patients compared with physiotherapy
      alone.

PMID- 17213238
TI  - A randomized controlled study of botulinum toxin A in the treatment of hemiplegic
      shoulder pain associated with spasticity.
AB  - OBJECTIVES: To assess the effects of botulinum toxin A (BT-A) on hemiplegic
      shoulder pain associated with spasticity. DESIGN: Randomized, double-blind,
      placebo-controlled study. SETTING: Outpatient clinic of a rehabilitation
      department. PARTICIPANTS: Patients, more than three months post stroke, with
      hemiplegic shoulder pain associated with shoulder adductor and elbow flexor
      spasticity, randomly assigned to BT-A or placebo. INTERVENTION: One-time
      injection of BT-A (500 units) into the pectoralis major and biceps brachii on the
      hemiplegic side. MAIN MEASURES: Visual analogue scale of shoulder pain (0 -10),
      shoulder adductor and elbow flexor tone using the Ashworth Scale and passive
      range of shoulder abduction. These were assessed at baseline, four weeks, eight
      weeks and 12 weeks post injection. RESULTS: Seventeen patients were enrolled,
      eight in the BT-A group and nine in the placebo group. At baseline, the median
      visual analogue scale score for shoulder pain was 6, the median Ashworth Scale
      shoulder adductor and elbow flexor spasticity score was 2 and the median range of
      shoulder abduction 76 degrees. Subjects who received BT-A showed significantly
      greater improvements in median shoulder adductor and elbow flexor Ashworth Scale
      scores than placebo at week 4 (P B / 0.01) but not at week 8 and 12. For shoulder
      pain and passive shoulder abduction range, all subjects showed postinjection
      improvements and no difference could be demonstrated between the two groups.
      DISCUSSION: Possible reasons for the negative finding in this study include the
      small sample size and the presence of causes of shoulder pain not related to
      spasticity which could have confounded outcome.

PMID- 17213239
TI  - Assertive rehabilitation for intracapsular fracture of the proximal femur.
AB  - OBJECTIVE: To study the impact of assertive conservative therapy on walking in
      frail elderly patients with intracapsular fracture of the proximal femaur.
      DESIGN: Prospective non-randomized controlled trial. SETTING: Two private
      geriatric rehabilitation hospitals. SUBJECTS: From October 1997 to December 2004,
      20 patients, not indicated for surgery, were treated with conservative therapy.
      There were 18 women and 2 men, and their ages were 87.1+/-4.2 (mean +/-SD) years.
      All of them could walk before hip fracture. INTERVENTIONS: Thirteen patients
      accepted our assertive therapy, which consisted of standing on the fractured limb
      and walking in parallel bars as soon as possible. Seven patients refused our
      methods and were conventionally treated; the injured limb was immobilized under
      skin traction, and then they gradually tried to use a wheelchair for pain
      reduction. MAIN MEASURES: We used the following measures before therapy and six
      months after: Merle d'Aubigne & Postel's Hip Score, Functional Independence
      Measure (FIM) and face pain scale. RESULTS: The two groups were similar
      demographically. All patients except one (n = 12) responded to our method and
      could walk. However, the patients treated with the conventional method (n = 7)
      did not recover the ability to walk. The mean FIM (transfer and locomotion, five
      items) was 18.2 +/-7.9 points in the former and 9.4 +/- 4.3 points in the latter.
      CONCLUSION: Assertive rehabilitation was more effective at restoring the
      ambulatory ability of frail elderly patients with intracapsular fracture of the
      hip than the conventional method.

PMID- 17213240
TI  - Pre-emptive swallowing stimulation in long-term intubated patients.
AB  - OBJECTIVE: To evaluate the effect of pre-emptive swallowing stimulation on the
      recovery of swallowing function in long-term intubated patients. DESIGN AND
      SUBJECTS: Patients in the intensive care unit intubated for at least 48 hours due
      to respiratory distress from March to August 2004 were randomly divided into two
      groups. Fifteen patients of mean age 55.39+/-17.9 years were stimulated
      (experimental group) and 18 patients of mean age 61.39+/-13.5 years were not
      stimulated (control group). The duration of intubation was 15.59+/-6.7 days in
      the experimental group and 15.79+/-6.5 days in the control group. Duration of
      stimulation in the experimental group was 7.39+/-3.6 days. After extubation, we
      compared the severity of dysphagia via video-fluoroscopic swallow study. RESULTS:
      There were no statistically significant differences in the percentage of
      aspiration and the swallowed volume between the two groups. However, oral transit
      time in the experimental group (0.379+/-0.07 seconds) was significantly shorter
      than that of the control group (0.839+/-0.10 seconds), and the oropharyngeal
      swallowing efficiency of the experimental group (73.39+/-17.4%/s) was
      significantly higher than that of the control group (50.19+/-13.0%/s).
      CONCLUSION: Pre-emptive swallowing stimulation during intubation assists in the
      recovery of swallowing function in long-term intubated patients.

PMID- 17213241
TI  - Goal-directed training: linking theories of treatment to clinical practice for
      improved functional activities in daily life.
AB  - BACKGROUND: Goal-directed training is an activity-based approach to therapy.
      Meaningful, client-selected goals are used to provide opportunities for problem
      solving and to indirectly drive the movements required to successfully meet the
      task demands. This is in contrast to interventions that focus on changing body
      functions. Here, the principles of goal-directed training will be studied through
      two case studies with the aim of linking theories of treatment to clinical
      practice. PRINCIPLES ILLUSTRATED: The approach is based on the dynamic systems
      motor control theory and occupation-based therapy models, which suggest that
      movement patterns emerge from the interaction between the person's abilities,
      environment and the goal. Motor learning principles are applied to structure and
      schedule practice. THEORY IN PRACTICE: Four components provide the basis for goal
      directed training: (1) selection of a meaningful goal; (2) analysis of baseline
      performance; (3) intervention/ practice regime; and (4) evaluation of outcome.
      Two individuals with acquired brain injury practised self-care tasks: eating and
      tying hair into a ponytail. Intensive training was undertaken over four weeks and
      the intervention outcome measured using the Goal Attainment Scale. CONCLUSIONS:
      The positive achievements in the self-care tasks illustrated that theories of
      motor control and motor learning can be applied to goal-directed training. The
      examples demonstrated that the approach could be applied to individuals with a
      range of abilities.

PMID- 17213242
TI  - Development of the Adelaide driving self-efficacy scale.
AB  - OBJECTIVE: To describe the development of the Adelaide Driving Self-Efficacy
      Scale (ADSES) and to report on its reliability and validity. METHODS: A set of 12
      driving behaviours, developed through literature review, clinical experience and
      expert review, were rated for self-efficacy using a Likert scale. Internal
      consistency was investigated using a Cronbach's alpha coefficient and construct
      validity by comparing ADSES scores of stroke and non-stroke drivers. Criterion
      related validity was examined by comparing ADSES scores with the result on a
      standardized on-road assessment. SETTING: A rehabilitation hospital in Adelaide,
      South Australia. PARTICIPANTS: Staff from the hospital and stroke patients from
      the rehabilitation unit. Data from a non-stroke sample (n -/ 79) and stroke
      patients (n -/ 81) were used to test internal consistency and construct validity.
      A separate group of 45 people recommended for a driving assessment, of whom 34
      were stroke patients, were used to test criterion validity. RESULTS: Cronbach's
      alpha coefficient was 0.98, indicating high internal consistency. The non-stroke
      and stroke groups showed significant differences in ADSES scores (t(158)-/ 5.5, P
      B < 0.05), demonstrating construct validity. Differences in ADSES scores for
      those participants who passed or failed the on-road assessment were significant
      for both the entire driving assessment group (t(43)-/ 3.2, P B < 0.05) and the
      stroke subgroup (t(43)-/ 3.2, P B < 0.05), indicating criterion validity.
      CONCLUSION: The ADSES has demonstrated internal consistency and construct
      validity with the stroke and non-stroke population. The scale demonstrated
      criterion validity in its relationship with outcome of an on-road driving
      assessment. It appears to be a reliable and valid measure of driving self
      efficacy.

PMID- 17213243
TI  - Quality of paediatric rehabilitation from the parent perspective: validation of
      the short Measure of Processes of Care (MPOC-20) in the Netherlands.
AB  - OBJECTIVE: In the present study we aim to assess the reliability and validity of
      the 20-item version of the Dutch Measure of Processes of Care (MPOC). DESIGN: The
      reliability, concurrent validity, predictive validity and construct validity of
      the Dutch MPOC-20 were determined. A subset of MPOC-20 data was extracted from a
      large Dutch MPOC (56-item version) database. SUBJECTS: Participants were 405
      mothers and 22 fathers of children aged 1-18 years recruited through nine
      paediatric rehabilitation centres in the Netherlands. MAIN MEASURES: The
      participants filled out the MPOC-20 items, the Client Satisfaction Questionnaire
      (CSQ), and two additional questions about satisfaction with services and the
      amount of stress they experienced. RESULTS: The internal consistency analyses
      (alphas 0.75-0.87) and the test-retest analyses (intraclass correlation
      coefficients (ICCs) 0.78-0.91) showed that the Dutch MPOC-20 is a reliable tool.
      The concurrent validity of the Dutch MPOC-20 was confirmed by positive
      correlations between MPOC-20 scale scores and the CSQ (r 0.39-0.69), and between
      MPOC-20 scale scores and an overall satisfaction variable (r 0.37-0.66). The
      predictive validity of the Dutch MPOC-20 was supported by moderately negative
      correlations between MPOC-20 scores and a stress variable (r -0.27 to -0.44). The
      construct validity of the Dutch MPOC-20 was confirmed by significant scale
      intercorrelations (r 0.41-0.84) and a factor analysis. CONCLUSIONS: The 20-item
      version of the MPOC (Dutch MPOC-20) is a reliable and valid measure of the family
      centredness of paediatric rehabilitation.

PMID- 17213244
TI  - The ability of the Biodex Stability System to distinguish level of function in
      subjects with a second-degree ankle sprain.
AB  - OBJECTIVE: To assess the capacity of the Biodex Stability System using a one-leg
      stance protocol to differentiate between injured and non-injured limbs and
      between level of disabilities. DESIGN: Cross-sectional study. SETTING: Military
      and civilian clinic. SUBJECTS: Thirty-four individuals with a second-degree
      lateral ankle sprain and 36 healthy subjects. METHODS AND MEASURES: Subjects were
      tested on the Stability System 30 days after injury using a one-leg stance
      protocol in the dynamic limit-of-stability mode. All subjects also filled out a
      disability questionnaire (Lower Extremity Functional Scale). The groups were
      compared based on the overall dynamic limit-of-stability score and its
      relationship with the score on the disability questionnaire was also examined.
      RESULTS: The overall dynamic limit-of-stability scores (subjects with a lateral
      ankle sprain: 13.0% (5.5)-26.0% (9.2); healthy subjects: 16.9% (7.9)-27.9% (9.6))
      clustered in the lower end of the theoretical range of 0-100%. Statistically
      significant differences in the overall dynamic limit-of-stability scores were
      found between the injured and non-injured limbs but group differences were small
      and clinically not relevant. No significant relationships were found between the
      overall dynamic limit-of-stability scores and the Lower Extremity Functional
      Scale scores (58.2 (11.8)) of the subjects with a lateral ankle sprain.
      CONCLUSIONS: The one-leg stance protocol carried out in the dynamic limit-of
      stability mode is very challenging and offers a very limited capacity to
      differentiate between injured and non-injured limbs. The main outcome of the
      Stability System does not appear to be a good indicator of the functional
      capacity of people with a lateral ankle sprain.

PMID- 17213245
TI  - Stress and depression in family carers following traumatic brain injury: the
      influence of beliefs about difficult behaviours.
AB  - OBJECTIVE: Difficult behaviours are significant contributors to the distress
      experienced by carers of people with a traumatic brain injury. This study
      investigated whether the beliefs carers hold about such behaviours also
      contribute to the distress. DESIGN: Questionnaire survey. PARTICIPANTS: Forty
      family carers recruited from Headway, a traumatic brain injury support
      organization. MAIN MEASURES: Zung's Self-Rating Depression Scale, Perceived
      Stress Scale, Social Support Questionnaire, a measure of the severity of
      difficult behaviours shown by the person cared for and two measures of carer
      beliefs about the behaviour (including the Controlling Beliefs Scale). RESULTS:
      Higher depression and stress scores were associated with more severe behaviours
      and less social support. Carer belief in their own ability to control the
      behaviours was associated with less stress. Belief that the behaviour was under
      the control of the person with traumatic brain injury and/or was motivated by
      hostile intentions was associated with more depression but less stress. Taken
      together, severity of behaviour and social support accounted for about 19% of the
      variance in both depression and stress scores. Carer beliefs accounted for
      another 5% of the depression scores, and another 11% of the stress scores.
      CONCLUSIONS: The results were consistent with the idea that carer beliefs about
      difficult behaviour contribute to carer distress, but longitudinal and treatment
      studies are needed to establish causality.

PMID- 17213246
TI  - Life satisfaction in individuals with a spinal cord injury and pain.
AB  - OBJECTIVE: To assess and describe life satisfaction in individuals with spinal
      cord injury (SCI) with regard to pain. DESIGN: A cross-sectional descriptive
      study of self-reported life satisfaction in individuals with SCI, with and
      without pain. SETTING: Spinal outpatient clinic. SUBJECTS: Two hundred and thirty
      patients with SCI were mailed a questionnaire. INTERVENTIONS: Mailed survey. MAIN
      MEASURES: Ratings of pain intensity, pain unpleasantness, mood, and life
      satisfaction (LiSat-9). RESULTS: In total 191 (83%) of the questionnaires were
      returned and analysed. Patients with pain experienced lower life satisfaction
      compared with individuals who were pain free. Continuous pain interfered to a
      greater extent than did intermittent pain. In logistic regression analysis the
      univariate relationship between pain and low life satisfaction was removed.
      Predictive for lower scores of life satisfaction were higher ratings of mood
      disorders. CONCLUSION: Life satisfaction is negatively affected in patients with
      SCI and pain compared to patients with SCI but without pain. Higher levels of
      anxiety and depression seem to be predictive for this decreased life
      satisfaction.

PMID- 17213247
TI  - Ecstasy versus alcohol: Tolstoy and the variations of unhappiness.

PMID- 17213249
TI  - Alcohol, ecstasy, Aldous Huxley's 'soma'.

PMID- 17213250
TI  - Commentary on a critique for the Journal of Psychopharmacology: NICE--excellence
      or eccentricity? Reflections on the z-drugs as hypnotics review.

PMID- 17213251
TI  - The comparative effectiveness of anti-TNF therapy and methotrexate in patients
      with psoriatic arthritis: 6 month results from a longitudinal, observational,
      multicentre study.
AB  - OBJECTIVES: To compare the response to treatment with tumour necrosis factor
      (TNF) inhibitors and methotrexate (MTX) monotherapy in patients with psoriatic
      arthritis (PsA) within a real-life clinical setting. METHODS: We analysed data
      from an ongoing longitudinal, observational multicentre study in Norway. Our data
      comprised 526 cases of patients with PsA who received either anti-TNF treatment
      (n = 146) or MTX monotherapy (n = 380) and were followed for at least 6 months
      with measures of disease activity, health status and utility scores. A propensity
      score was computed to adjust for channelling bias. The changes in measures of
      disease activity and health-related quality of life from baseline to 3- and 6
      month follow-up were compared between the groups with adjustments for the
      baseline value of the dependent variable and the propensity score (analyses of
      covariance (ANCOVA)). RESULTS: The groups were significantly different at
      baseline with respect to demographic and disease activity measures. The variables
      included in the propensity score were age, sex, number of previous disease
      modifying anti-rheumatic drugs (DMARDs), presence of erosive disease, treatment
      centre and investigator's global assessment. The adjusted changes at 6 months
      were significantly larger in the anti-TNF group for ESR, DAS-28, M-HAQ, patient's
      assessments of pain, fatigue and global disease activity on a visual analogue
      scale (VAS) and 4 out of 8 SF-36 dimensions. CONCLUSIONS: Clinical improvement
      was superior with TNF inhibitors compared to MTX monotherapy in patients with
      PsA, when assessed in this setting of daily clinical practice.

PMID- 17213252
TI  - Autoinflammatory gene mutations in Behcet's disease.
AB  - BACKGROUND: Behcet's disease (BD) shares clinical features with well-recognised
      autoinflammatory disorders. In addition, mutations in genes for familial
      Mediterranean fever and tumour necrosis factor receptor-associated periodic
      syndrome have been reported to have increased in patients with BD. PATIENTS AND
      METHODS: DNA samples from 97 patients with BD and 51 matched healthy controls
      were analysed for the mevalonate kinase (MVK), cold-induced autoinflammatory
      syndrome 1 (CIAS1) and proline/serine/threonine phosphatase-interacting protein 1
      (PSTPIP1) genes, responsible for mevalonate kinase deficiency (MKD), cryopyrin
      associated periodic syndromes (CAPS) and pyogenic sterile arthritis, pyoderma
      gangrenosum and acne (PAPA) syndrome, respectively. Over 90% of known mutations
      were screened using restriction fragment length polymorphism analysis and/or
      sequencing. RESULTS: Two patients had paired mutations in the MVK gene (genotypes
      V377I/V377I and V377I/S135L) and displayed typical features of BD and MKD.
      Another was heterozygotic for the V377I genotype. The V198M mutation in the CIAS1
      gene was identified in one patient with typical BD but no symptoms of CAPS. No
      mutations were identified in the control group. PSTPIP1 analysis revealed a new
      exon 10 insertion variant (c.741+33_741+34insGT) in 2 of 97 patients and in 1 of
      51 controls (p>0.05), indicating that it is a polymorphism rather than a true
      mutation. DISCUSSION: This study could not demonstrate any significant increases
      in MVK, CIAS1 or PSTPIP1 mutations in patients with BD as compared with controls.

PMID- 17213253
TI  - Development of additional autoimmune diseases in a multiethnic cohort of patients
      with systemic lupus erythematosus with reference to damage and mortality.
AB  - OBJECTIVES: To determine the prevalence of other autoimmune diseases (AID) in
      black, Caucasian and South Asian patients with systemic lupus erythematosus (SLE)
      compared with the prevalence of these AID in the UK population, and to assess the
      impact of these additional AID on damage scores and mortality. METHODS: The
      prevalence and chronology of development of additional AID in SLE patients was
      determined by case note review. Comparisons were made with prevalence data for
      AID in the general UK population. The impact of additional AID on mortality and
      damage scores at up to 10 years was determined in the index cases (patients who
      developed another AID either in the same year or within 5 years of onset of SLE)
      compared with controls matched for sex, age, ethnicity and year of onset of SLE.
      RESULTS: There was no significant difference in the total number of AID that
      developed in patients from each ethnic group but differences in the frequency of
      some AID were noted. Mortality and damage scores were worse at 5 years in the
      study cases than the controls, particularly in the peripheral vascular category.
      CONCLUSION: Patients with SLE might develop other AID that could complicate
      management of SLE by having an adverse impact on damage scores and mortality.

PMID- 17213254
TI  - How do the EQ-5D, SF-6D and the well-being rating scale compare in patients with
      ankylosing spondylitis?
AB  - PURPOSE: To compare aspects of validity of EuroQol-5 Dimensions (EQ-5D) and Short
      Form-6 Dimensions (SF-6D), two indirect utility instruments, and the well-being
      rating scale (RS) in ankylosing spondylitis (AS). METHODS: EQ-5D, SF-6D and RS
      were available for 254 patients fulfilling modified New York criteria. 134
      patients were part of an observational cohort and 120 were part of a randomised
      controlled trial (RCT). Aspects of validity assessed were truth (agreement and
      correlation with external health measures) and discrimination (differentiation
      between health states, repeatability and detection of treatment effect). RESULTS:
      Median (range) values were 0.69 (-0.08-1.00) for the EQ-5D, 0.65 (0.35-0.95) for
      the SF-6D and 0.65 (0.14-1.00) for the RS. Agreement (intraclass correlation
      coefficient) was moderate (0.46-0.55). Instruments correlated equally with
      disease activity, functioning and quality of life. The SF-6D showed smaller
      average differences in utility between patients with better and worse disease
      compared with the EQ-5D and the RS. The smallest detectable difference (SDD) (in
      the control group of RCT) was 0.36, 0.17 and 0.33 for EQ-5D, SF-6D and RS,
      respectively. The ability to detect treatment effect (in the intervention trial)
      showed standardised effect sizes that were moderate for EQ-5D and SF-6D (0.63 and
      0.64) and low for the RS (0.23). CONCLUSION: In patients with AS, EQ-5D, SF-6D
      and the RS correlate equally well with external measures of health, but have
      different psychometric properties. The SDD is most favourable for the SF-6D, but
      it discriminates less well between patients with different disease severities.
      The RS has a poorer ability to detect treatment effects. It is difficult to
      recommend one of the instruments.

PMID- 17213255
TI  - Meeting report: mitochondrial DNA and cancer epidemiology.

PMID- 17213256
TI  - Combinations of tomato and broccoli enhance antitumor activity in dunning r3327-h
      prostate adenocarcinomas.
AB  - The consumption of diets containing 5 to 10 servings of fruits and vegetables
      daily is the foundation of public health recommendations for cancer prevention,
      yet this concept has not been tested in experimental models of prostate cancer.
      We evaluated combinations of tomato and broccoli in the Dunning R3327-H prostate
      adenocarcinoma model. Male Copenhagen rats (n=206) were fed diets containing 10%
      tomato, 10% broccoli, 5% tomato plus 5% broccoli (5:5 combination), 10% tomato
      plus 10% broccoli (10:10 combination) powders, or lycopene (23 or 224 nmol/g
      diet) for approximately 22 weeks starting 1 month prior to receiving s.c. tumor
      implants. We compared the effects of diet to surgical castration (2 weeks before
      termination) or finasteride (5 mg/kg body weight orally, 6 d/wk). Castration
      reduced prostate weights, tumor areas, and tumor weight (62%, P<0.001), whereas
      finasteride reduced prostate weights (P<0.0001), but had no effect on tumor area
      or weight. Lycopene at 23 or 224 nmol/g of the diet insignificantly reduced tumor
      weights by 7% or 18%, respectively, whereas tomato reduced tumor weight by 34%
      (P<0.05). Broccoli decreased tumor weights by 42% (P<0.01) whereas the 10:10
      combination caused a 52% decrease (P<0.001). Tumor growth reductions were
      associated with reduced proliferation and increased apoptosis, as quantified by
      proliferating cell nuclear antigen immunohistochemistry and the ApopTag assay.
      The combination of tomato and broccoli was more effective at slowing tumor growth
      than either tomato or broccoli alone and supports the public health
      recommendations to increase the intake of a variety of plant components.

PMID- 17213257
TI  - The Anti-Mullerian hormone and ovarian cancer.
AB  - The Anti-Mullerian hormone (AMH), which is produced by fetal Sertoli cells, is
      responsible for regression of Mullerian ducts, the anlagen for uterus and
      Fallopian tubes, during male sex differentiation. Ovarian granulosa cells also
      secrete AMH from late in fetal life. The patterns of expression of AMH and its
      type II receptor in the post-natal ovary indicate that AMH may play an important
      role in ovarian folliculogenesis. Recent advances in the physiological role of
      AMH has stimulated interest in the significance of AMH as a diagnostic marker and
      therapeutic agent for ovarian cancer. Currently, AMH has been shown to be a
      circulating marker specifically for granulosa cell tumour (GCT). Its diagnostic
      performance seems to be very good, with a sensitivity ranging between 76 and 93%.
      In patients treated for GCT, AMH may be used post-operatively as marker for the
      efficacy of surgery and for disease recurrence. Based on the physiological
      inhibitory role of AMH in the Mullerian ducts, it has been proposed that AMH may
      inhibit epithelial ovarian cancer cell both in vitro and in vivo. These
      observations will be the basis for future research aiming to investigate the
      possible clinical role of AMH as neo-adjuvant, or most probably adjuvant, therapy
      for ovarian cancer.

PMID- 17213258
TI  - Concerning: is screening for tuberculosis acceptable to immigrants? A qualitative
      study.

PMID- 17213259
TI  - Weight estimation in resuscitation: is the current formula still valid?
AB  - OBJECTIVES: To gather data on the ages and weights of paediatric patients between
      1 and 10 years of age, and to compare these data with the current weight
      estimation formula weight(kg) = 2(age+4). If a significant difference was found,
      the data would be used to derive a more accurate formula. DESIGN: Retrospective
      study using data collected from paediatric attendances at an emergency department
      (ED). SETTING: A large ED in a major UK city, treating both children and adults.
      PATIENTS: 17 244 children aged 1-10 years, attending the ED between June and
      December 2005. MAIN OUTCOME MEASURES: Weight difference between the measured
      weight and the expected weight, the latter given by weight = 2(age+4). RESULTS:
      The weights of seriously ill children were recorded in only 41.5% of cases,
      necessitating a weight estimate in the remainder. The formula weight = 2(age+4)
      underestimated children's weights by a mean of 18.8% (95% confidence interval
      (95% CI) 18.42% to 19.18%). Using linear regression and analysis of each
      individual age group, ten new formulas were tested. Of these formulas, weight(kg)
      = 3(age)+7 proved the most accurate with a mean underestimate of just 2.48% (95%
      CI 2.17% to 2.79%). CONCLUSIONS: Weight estimation remains of paramount
      importance in paediatric resuscitation. This study shows that the current
      estimation formula provides a significant underestimate of children's weights.
      When used to calculate drug and fluid dosages, this may lead to the under
      resuscitation of a critically ill child. The formula weight(kg) = 3(age)+7
      provided a safe and more accurate estimate of the weight of today's child.

PMID- 17213260
TI  - Missed opportunities to vaccinate children admitted to a paediatric tertiary
      hospital.
AB  - BACKGROUND: Inequalities in vaccine uptake exist. Studies suggest paediatric
      inpatients have lower rates of immunisation uptake than the general population.
      Various UK policies advocate opportunistic immunisation. AIM: To evaluate
      practice within a paediatric tertiary hospital in identifying and facilitating
      vaccination of inpatients who were not fully immunised. METHODS: Case notes for
      225 inpatients were examined. Thirty staff of various professions and grades were
      interviewed. Policies, forms and documents used in the hospital were reviewed.
      RESULTS: Immunisation status was recorded for 71% of children admitted, but for
      69% of these immunisations were documented as "up-to-date" without any further
      information recorded. At least 20% of inpatients were incompletely immunised, but
      very little was done to facilitate vaccination. There was no training for staff
      either in giving advice or in administering vaccines and staff views differed
      regarding the hospital's role in immunisations. While there were guidelines for
      specific groups of patients, there were no general immunisation policies.
      Incorrect and out-of-date immunisation schedules were found on documents.
      CONCLUSIONS: Opportunities to immunise children continue to be missed by all
      levels of health care service provision. Tertiary centres have a role to play in
      supporting primary care services to ensure that these vulnerable children are
      appropriately immunised. Measures are being taken to address the problems
      identified in this study and we strongly suspect that other hospitals in the UK
      ought to be confronting these issues as well.

PMID- 17213261
TI  - Hyponatraemia and hypokalaemia during intravenous fluid administration.
AB  - BACKGROUND: Hospital-acquired hyponatraemia is associated with excessive volumes
      of hypotonic intravenous fluids and can cause death or permanent neurological
      deficit. METHODS: A cross-sectional survey was carried out in 17 hospitals on all
      children receiving intravenous fluids during 1 day of a specified week in
      December 2004. RESULTS: 77 of 99 children receiving intravenous fluids received
      hypotonic solutions and 38% received >105% of fluid requirements. 21 of 86
      children were hyponatraemic, but the electrolytes of only 79% had been checked in
      the preceding 48 h. CONCLUSIONS: Intravenous fluids should be used with caution
      as regards the tonicity and volume administered, and with appropriate monitoring
      of serum electrolytes.

PMID- 17213262
TI  - Prevalence and predictors of antiretroviral drug resistance in newly diagnosed
      HIV-1 infection.
AB  - OBJECTIVES: To determine prevalence and predictors of antiretroviral drug
      resistance in newly diagnosed individuals with HIV-1 infection, using a
      systematic approach to avoid selection bias. METHODS: Plasma samples from all
      persons diagnosed HIV-1 seropositive at a large London centre between April 2004
      and February 2006 underwent sequencing of HIV-1 reverse transcriptase (RT) and
      protease genes. Subtype was assigned by phylogenetic analysis. Resistance was
      scored according to the IAS-USA list (2005) modified to include T215revertants
      and exclude isolated E44D or V118I and minor protease mutations. Recent
      seroconversion was identified by HIV antibody avidity testing. RESULTS: The
      cohort of 239 included 169 (70.7%) males, 126 (52.7%) homosexuals, 118 (49.5%)
      persons of white ethnicity and 144 (60.0%) persons born outside the UK. Subtypes
      included B 134 (56.1%), C 46 (19.2%), A 17 (7.1%), other non-B 42 (17.6%). The
      prevalence of resistance mutations was 17/239 (7.1%; 95% confidence interval 4.5
      11.1%), comprising 10/239 (4.2%) nucleoside/nucleotide RT inhibitor (NRTI); 4/239
      (1.7%) non-nucleoside RT inhibitor (NNRTI) and 4/239 (1.7%) protease inhibitor
      (PI) associated mutations. Dual-class (NRTI + PI) resistance mutations were
      detected in 1/239 (0.4%) person. The prevalence of resistance mutations was 7/85
      (8.2%) and 10/154 (6.5%) in persons with recent and established infection,
      respectively. In multivariate analysis, having been born in the UK and high CD4
      count, but not gender, age, risk group, ethnicity or subtype, were independent
      predictors of resistance. CONCLUSIONS: In an unselected UK cohort, subtypes other
      than B accounted for 43.9% of new HIV-1 diagnoses. The prevalence of resistance
      mutations was 7.1% and highest in those born in the UK.

PMID- 17213263
TI  - Antiretroviral activity of pegylated interferon alfa-2a in patients co-infected
      with HIV/hepatitis C virus.
AB  - OBJECTIVES: To evaluate the early anti-HIV activity of pegylated interferon (PEG
      IFN) alfa-2a and ribavirin in HIV/hepatitis C virus (HCV) co-infected patients
      not receiving antiretroviral therapy. PATIENTS AND METHODS: In 19 patients with
      baseline plasma HIV load (HIV-RNA) >1000 copies/mL treated with PEG-IFN alfa-2a
      and ribavirin, HIV-RNA and T-cell subsets were measured at baseline and 2, 4 and
      12 weeks after initiation of anti-HCV therapy. RESULTS: We observed a significant
      HIV-RNA decrease (>1 log(10) copies/mL) through week 12 of anti-HCV treatment.
      The magnitude of HIV-RNA decline was associated with baseline HIV-RNA, CD4 count
      and PEG-IFN weight-adjusted dose. CONCLUSIONS: A significant early anti-HIV
      activity of PEG-IFN alfa-2a was observed. Such an effect warrants further
      clinical evaluation in the management of co-infected patients.

PMID- 17213264
TI  - In vitro activity of tigecycline against clinical isolates of Acinetobacter
      baumannii and Stenotrophomonas maltophilia.

PMID- 17213265
TI  - Impact of imipenem resistance on mortality in patients with Acinetobacter
      bacteraemia.
AB  - OBJECTIVES: To investigate the impact of imipenem resistance on the mortality
      rate among patients with Acinetobacter bacteraemia. METHODS: A retrospective,
      pairwise-matched (1:1), risk-adjusted (age, Pitt bacteraemia score) cohort study
      was performed at three tertiary care hospitals in Korea from January 2000 to June
      2005. RESULTS: Forty patients with imipenem non-susceptible Acinetobacter
      bacteraemia (INAB group) and 40 matched subjects (1:1 ratio) with imipenem
      susceptible Acinetobacter bacteraemia (ISAB group) were included. Both groups had
      similar clinical features related to the severity of illness. The 30 day
      mortality rate was higher in the INAB group (57.5%) than the ISAB group (27.5%)
      (P = 0.007). The rate of discordant antimicrobial therapy was higher in the INAB
      group (65.0%) than the ISAB group (20.0%) (P < 0.001). The 30 day mortality rate
      was higher in the patients with discordant antimicrobial therapy (67.6%) than
      concordant antimicrobial therapy (23.9%) (P < 0.001). Multivariate analysis
      showed that age, the Pitt bacteraemia score, immunosuppressive status, and
      discordant antimicrobial therapy were independent risk factors for 30 day
      mortality among patients with Acinetobacter bacteraemia (P < 0.05). When
      discordant antimicrobial therapy was excluded in the multivariate analysis, the
      imipenem resistance was associated with 30 day mortality (P = 0.005).
      CONCLUSIONS: Imipenem resistance has a significant impact on the mortality rate
      among patients with Acinetobacter bacteraemia, and this is mainly attributable to
      the higher rate of discordant antimicrobial therapy.

PMID- 17213266
TI  - The spectrum of antimicrobial activity of the bacteriocin subtilosin A.
AB  - BACKGROUND: Bacterocins are antimicrobial peptides produced by bacteria with a
      relatively narrow range of activity against closely related organisms. Subtilosin
      A is a bacteriocin produced by Bacillus subtilis that has activity against
      Listeria monocytogenes, which might indicate antimicrobial activity unusual for
      bacteriocins. OBJECTIVES: To examine the antimicrobial activity and factors
      affecting the activity of subtilosin A against a range of potentially pathogenic
      bacteria. METHODS: The peptide was purified from cultures of B. subtilis and the
      MIC determined for 18 species of bacteria using a microdilution methodology. The
      extent of capsule formation was determined using microscopic examination of cells
      mounted in India ink. Protease mutants of a susceptible bacteria and mild heat
      shock were used to examine the effect of environmental stress on subtilosin A
      activity. RESULTS: Subtilosin A proved to have antimicrobial activity against a
      wide range of bacteria including Gram-positive and Gram-negative bacteria and
      both aerobes and anaerobes. The peptide was less effective against capsulated
      forms of two Gram-negative bacteria than the non-capsulated strains of either.
      Heat shock but not protease activity also altered the effectiveness of the
      bacteriocin. CONCLUSIONS: Subtilosin A has limited antimicrobial activity against
      a number of human pathogens which, combined with its relative ineffectiveness
      against some capsulated pathogens, may limit its usefulness as a human
      therapeutic.

PMID- 17213267
TI  - Role of ABC transporter MRPA, gamma-glutamylcysteine synthetase and ornithine
      decarboxylase in natural antimony-resistant isolates of Leishmania donovani.
AB  - OBJECTIVES: The resistance of clinical isolates of Leishmania donovani to sodium
      antimony gluconate (SAG), the mainstay of treatment in Indian visceral
      leishmaniasis, has become a critical issue in India. The present work
      investigates the mechanism of resistance to SAG in parasites isolated from
      patients who are unresponsive to SAG. METHODS AND RESULTS: Susceptibility to SAG
      as determined in vitro with intracellular amastigotes correlated well with the
      clinical response. The ABC transporter gene MRPA was amplified in resistant field
      isolates as part of an extrachromosomal circle. Co-amplification of the pterin
      reductase gene (PTR1) and MRPA suggests amplification of the H locus in SAG
      resistant isolates. Amplification of MRPA was correlated to increased RNA as
      determined by real-time PCR. MRPA is an ABC-thiol transporter, and cysteine and
      glutathione were increased in the resistant isolates. Ornithine decarboxylase (a
      rate limiting enzyme in polyamine biosynthesis), and gamma-glutamylcysteine
      synthetase (a rate limiting enzyme in glutathione biosynthesis), the two building
      blocks of the main cellular thiol trypanothione, were overexpressed in some of
      the resistant isolates. CONCLUSIONS: A variety of resistance mechanisms to SAG,
      most of them consistent with a model based on the study of resistance in vitro,
      were present in clinical isolates from the same geographical region.

PMID- 17213268
TI  - A novel ex vivo skin model to study the susceptibility of the dermatophyte
      Trichophyton rubrum to photodynamic treatment in different growth phases.
AB  - BACKGROUND: Dermatophytes are fungi that can cause infections of skin, hair and
      nails because of their ability to feed on keratin. Superficial mycoses are among
      the most prevalent infectious diseases worldwide. Two important restrictions of
      current therapeutic options are the recurrence of the infection and prolonged
      treatment. This is especially true for infections caused by Trichophyton rubrum,
      a widely distributed dermatophyte. The application of photosensitizers for
      treatment of fungal infections is, within the field of photodynamic treatment
      (PDT), relatively new. Recently, we demonstrated that the porphyrins 5,10,15
      tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine trichloride (Sylsens B) and
      deuteroporphyrin monomethylester (DP mme) were excellent photosensitizers towards
      T. rubrum when using red light. OBJECTIVES AND METHODS: To evaluate the
      photodynamic effectiveness of the porphyrins in a situation that mimics the
      clinical situation, we developed an ex vivo model using human stratum corneum.
      This model offers the possibility of applying PDT at different time points during
      the germination and subsequent development of T. rubrum microconidia. The model
      was used for two different incubation media, Dulbecco's modified Eagle medium
      (DMEM) and distilled water. RESULTS AND CONCLUSIONS: We demonstrated that the PDT
      susceptibility of T. rubrum depended on the time of PDT application after spore
      inoculation. A decrease in susceptibility was observed with increasing time of
      PDT application for both photosensitizers in DMEM. Changing the incubation medium
      to distilled water resulted in an increased fungicidal effect for Sylsens B and
      in a decreased effect for DP mme. We conclude that T. rubrum is susceptible to
      PDT in a situation that mimics the clinical situation. The fungicidal effect of
      PDT on fungal spores is of particular importance.

PMID- 17213269
TI  - The G2964A 3'-untranslated region polymorphism of the signal transducer and
      activator of transcription 6 gene is associated with endometriosis in South
      Indian women.
AB  - BACKGROUND: The aim of the study was to test whether the signal transducer and
      activator of transcription 6 (STAT6) gene influences the risk of developing
      endometriosis. METHODS: The single-nucleotide polymorphism, G2964A, in the 3'
      untranslated region (UTR) of the STAT6 gene was tested for association in a case
      control study of 232 affected women and 210 women with no evidence of disease.
      All the women were infertile, ascertained from the same infertility clinic and of
      South Indian origin. The genotype frequencies of this polymorphism were compared
      using PCR and sequencing analysis. RESULTS: There were statistically significant
      differences in the genotype distributions (P = 0.002) and allele frequencies (P =
      0.0002) between the cases and controls, according to codominant, dominant and
      recessive genotype models. CONCLUSIONS: We report for the first time an
      association between the STAT6 G2964A 3'-UTR polymorphism and endometriosis in
      South Indian women. This finding suggests that STAT6 may contribute to disease
      susceptibility in endometriosis, which carries an extra interest as the gene lies
      in a region which has been implicated, albeit weakly, in a previous genomewide
      scan.

PMID- 17213270
TI  - Conservative treatment for patent ductus arteriosus in the preterm.
AB  - BACKGROUND: A patent ductus arteriosus (PDA) is common among preterms, and
      prophylactic medical treatment has been advocated as the first-line approach.
      Conservative treatment may result in similar outcome, but without exposure to the
      harmful side effects of medication. A retrospective analysis revealed a ductal
      closure rate of 94% after conservative treatment with adjustment of ventilation
      (lowering the inspiratory time and increasing positive end expiratory pressure)
      and fluid restriction. OBJECTIVE: To study prospectively over one year the rate
      of PDA closure, and morbidity and mortality following conservative treatment.
      METHOD: Prospective study (1 January 2005 - 31 December 2005) including 30
      newborns <or=30 weeks' gestation, all of whom were being ventilated and required
      surfactant. Echocardiography was performed 48-72 h after birth. Clinically
      important PDA was conservatively treated as described above. The percentage of
      children with PDA, ductal ligation and major complications was determined.
      RESULTS: Ten neonates (33%) developed a clinical important PDA. Following
      conservative treatment the duct closed in all neonates (100%), and none required
      ductal ligation or medical treatment. The rates of major complications were no
      higher than those reported by the Vermont Oxford Network and in the literature.
      CONCLUSION: The managed care plan resulted in an overall ductal closure rate of
      100%. These results suggest that conservative treatment of PDA is a worthy
      alternative to prophylactic medical treatment.

PMID- 17213271
TI  - Mortality patterns among very preterm babies: a comparative analysis of two
      European regions in France and England.
AB  - OBJECTIVE: To explore the differences in outcome of very preterm pregnancies
      between two geographically defined populations in Europe with similar
      socioeconomic characteristics and healthcare provision but different
      organisational arrangements for perinatal care. DESIGN: Prospective cohort study.
      SETTING: Nord Pas-de-Calais (NPC), France, and Trent, UK. PARTICIPANTS: All
      pregnancy outcomes 22(+0) to 32(+6) weeks' gestational age for resident mothers.
      OUTCOME MEASURES: Mortality patterns (antepartum death, intrapartum death, labour
      ward death and neonatal unit death) among very preterm babies were analysed by
      region. Multinomial logistic regression was used to model regional differences
      for a variety of pregnancy outcomes and to adjust for regional differences in the
      organisation of perinatal care. RESULTS: Delivery of very preterm infants was
      significantly higher in Trent compared with NPC (1.9% v 1.5% of all births,
      respectively (p<0.001)). Stillbirth rate was significantly higher in NPC than in
      Trent (23.0%, 95% CI 20.0% to 26.5% v 14.4%, 95% CI 12.3% to 16.6%, respectively
      (p<0.001)) and survival to discharge was higher in Trent than in NPC (74.6%, 95%
      CI 71.9% to 77.1% v 66.7%, 95% CI 63.3% to 69.9%, respectively (p<0.001)).
      Probability of intrapartum and labour ward death in NPC was more than five times
      higher than Trent (relative risk 5.3, 95% CI 2.2 to 13.1 (p<0.001)). CONCLUSION:
      The high rate of very preterm deliveries and the larger proportion of these
      infants recorded as live born in Trent appear to be the cause of the excess
      neonatal mortality seen in the routine statistics. Information about very preterm
      babies (not usually included in routine statistics) is vital to avoid
      inappropriate interpretation of international perinatal and infant data. This
      study highlights the importance of including deaths before transfer to neonatal
      care and emphasises the need to include the outcome of all pregnancies in a
      population in any comparative analysis.

PMID- 17213272
TI  - Plasma levels of active ghrelin until 8 weeks after birth in preterm infants:
      relationship with anthropometric and biochemical measures.
AB  - This study investigated the relationship between plasma levels of ghrelin and
      postnatal growth in preterm infants. The levels of active ghrelin in cord blood
      and in plasma in 25 very low birthweight (VLBW) infants were measured. The
      results indicate that the levels of circulating active ghrelin markedly increases
      after birth in VLBW infants, and suggest that the increased levels of ghrelin
      reflects the maturation of ghrelin production in the stomach and an increased
      physiological need for ghrelin.

PMID- 17213273
TI  - Prevalence of permanent neonatal diabetes in Slovakia and successful replacement
      of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers.
AB  - CONTEXT: Mutations in the KCNJ11 and ABCC8 genes encoding the pancreatic beta
      cell K(ATP) channel have recently been shown to be the most common cause of
      permanent neonatal diabetes mellitus (PNDM). Information regarding the frequency
      of PNDM has been based mainly on nonpopulation or short-term collections only.
      Thus, the aim of this study was to identify the incidence of PNDM in Slovakia and
      to switch patients to sulfonylurea (SU) where applicable. DESIGN: We searched for
      PNDM patients in the Slovak Children Diabetes Registry. In insulin-treated
      patients who matched the clinical criteria for PNDM, the KCNJ11 or ABCC8 genes
      were sequenced, and mutation carriers were invited for replacement of insulin
      with SU. RESULTS: Eight patients with diabetes onset before the sixth month of
      life without remission were identified since 1981, which corresponds to the PNDM
      incidence in Slovakia of one case in 215,417 live births. In four patients, three
      different KCNJ11 mutations were found (R201H, H46Y, and L164P). Three patients
      with the KCNJ11 mutations (R201H and H46Y) were switched from insulin to SU,
      decreasing their glycosylated hemoglobin from 9.3-11.0% on insulin to 5.7-6.6% on
      SU treatment. One patient has a novel V86A mutation in the ABCC8 gene and was
      also substituted with SU. CONCLUSIONS: PNDM frequency in Slovakia is much higher
      (one in 215,417 live births) than previously suggested from international
      estimates (about one in 800,000). We identified one ABCC8 and four KCNJ11
      mutation carriers, of whom four were successfully transferred to SU, dramatically
      improving their diabetes control and quality of life.

PMID- 17213274
TI  - Effects of the type 2 diabetes-associated PPARG P12A polymorphism on progression
      to diabetes and response to troglitazone.
AB  - CONTEXT: The common P12A polymorphism in PPARG (a target for thiazolidinedione
      medications) has been consistently associated with type 2 diabetes. OBJECTIVE: We
      examined whether PPARG P12A affects progression from impaired glucose tolerance
      to diabetes, or responses to preventive interventions (lifestyle, metformin, or
      troglitazone vs. placebo). PATIENTS: This study included 3548 Diabetes Prevention
      Program participants. DESIGN: We performed Cox regression analysis using genotype
      at PPARG P12A, intervention, and their interactions as predictors of diabetes
      incidence. We also genotyped five other PPARG variants implicated in the response
      to troglitazone and assessed their effect on insulin sensitivity at 1 yr.
      RESULTS: Consistent with prior cross-sectional studies, P/P homozygotes at PPARG
      P12A appeared more likely to develop diabetes than alanine carriers (hazard
      ratio, 1.24; 95% confidence interval, 0.99-1.57; P=0.07) with no interaction of
      genotype with intervention. There was a significant interaction of genotype with
      body mass index and waist circumference (P=0.03 and 0.002, respectively) with the
      alanine allele conferring less protection in more obese individuals. Neither
      PPARG P12A nor five other variants significantly affected the impact of
      troglitazone on insulin sensitivity in 340 participants at 1 yr. CONCLUSIONS: The
      proline allele at PPARG P12A increases risk for diabetes in persons with impaired
      glucose tolerance, an effect modified by body mass index. In addition, PPARG P12A
      has little or no effect on the beneficial response to troglitazone.

PMID- 17213275
TI  - Plasma concentration of pigment epithelium-derived factor in patients with
      diabetic retinopathy.
AB  - CONTEXT: Pigment epithelium-derived factor (PEDF) is a strong inhibitor of
      angiogenesis. Eyes with diabetic retinopathy have low levels of ocular PEDF;
      however, the PEDF levels in the blood of diabetics have still not been
      determined. OBJECTIVES: Our objective was to determine the plasma levels of PEDF
      in diabetic patients and to determine the relationship with the stage of the
      diabetic retinopathy. DESIGN AND SETTING: This study was designed as a cross
      sectional, institutional study. PATIENTS OR OTHER PARTICIPANTS: A total of 145
      Japanese were studied; 112 had type 2 diabetes mellitus, and 33 were healthy
      controls. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: The
      plasma level of PEDF was measured by ELISA, and the stage of diabetic retinopathy
      was determined by ophthalmic examinations. Clinical systemic status of diabetic
      patients was also examined. RESULTS: The plasma PEDF level in diabetic patients
      (6.68 +/- 0.54 microg/ml; mean +/- sem) was significantly higher than that in
      controls (4.38 +/- 0.59 microg/ml, P = 0.03), and the level was especially high
      in patients with proliferative diabetic retinopathy (7.78 +/- 0.98 microg/ml; n =
      45; P = 0.005). The gender (P = 0.03), blood urea nitrogen (P = 0.005), and
      triglycerides (P = 0.04) were significant and independent determinants of plasma
      PEDF levels in diabetic patients. CONCLUSIONS: The PEDF level in the plasma was
      significantly elevated in diabetic patients, especially those with proliferative
      diabetic retinopathy. High levels of PEDF in the plasma may be related to the
      progression of diabetic retinopathy.

PMID- 17213276
TI  - Postprandial lipoprotein metabolism in familial hypobetalipoproteinemia.
AB  - OBJECTIVE: Familial hypobetalipoproteinemia (FHBL) is an autosomal codominantly
      inherited disorder of lipoprotein metabolism characterized by decreased plasma
      concentrations of low-density lipoprotein-cholesterol and apolipoprotein (apo) B.
      We examined the effect of truncated apoB variants (<apoB-48) causing FHBL on
      postprandial triglyceride-rich lipoprotein (TRL) metabolism. METHODS AND RESULTS:
      A standardized oral fat load was given after a 12-h fast to six heterozygous
      [apoB-6.9 (n=3), apoB-25.8 (n=1), apoB-40.3 (n=2)] FHBL subjects and 10
      normolipidemic controls. Plasma was obtained every 2 h for 10 h. Large TRLs
      [containing chylomicrons (CM)] and small TRLs (containing CM remnants) were
      isolated by ultracentrifugation. Compared with controls, FHBL subjects had
      significantly decreased fasting plasma cholesterol (2.3+/-0.5 vs. 4.8+/-0.5
      mmol/liter), triglyceride (0.4+/-0.3 vs. 1.5+/-0.5 mmol/liter), low-density
      lipoprotein-cholesterol (0.6+/-0.4 vs. 3.0+/-0.5 mmol/liter), and apoB (0.22+/
      0.05 vs. 0.95+/-0.14 g/liter) concentrations (all P<0.001). The postprandial
      incremental area under the curve in FHBL subjects was decreased for large TRL
      triglyceride (-61%; P<0.005), small TRL-cholesterol (-86%; P<0.001), and small
      TRL-triglyceride (-86%; P<0.001) relative to controls. Multicompartmental
      modeling analysis showed that the delay time of apoB-48 was shorter and that apoB
      48 production was decreased in FHBL subjects compared with controls. CONCLUSIONS:
      We have demonstrated that heterozygous FHBL subjects with apoB truncations
      shorter than apoB-48, and therefore only a single fully-functional apoB-48
      allele, have decreased TRL production but normal postprandial TRL particle
      clearance.

PMID- 17213277
TI  - Molecular and clinical characterization of Y chromosome microdeletions in
      infertile men: a 10-year experience in Italy.
AB  - CONTEXT: An explosive growth in Y chromosome long arm (Yq) microdeletion testing
      demand for male infertility occurred in the past few years. However, despite the
      progresses in the biology of this chromosome, a number of molecular and clinical
      concerns are not supported by definitive data. OBJECTIVE: The objective was to
      provide information on the type and prevalence of microdeletions in infertile
      males, indication for testing, genotype-phenotype correlation, sperm
      aneuploidies, and genetic counseling. DESIGN AND SETTING: We performed a
      prospective study from January 1996 to December 2005 in an academic clinic.
      PATIENTS: We studied 3073 consecutive infertile men, of which 625 were affected
      by nonobstructive azoospermia and 1372 were affected by severe oligozoospermia.
      Ninety-nine patients with microdeletions are described here. MAIN OUTCOME
      MEASURES: Yq microdeletions, seminal analysis, reproductive hormones, testicular
      cytology/histology, and sperm sex chromosomes aneuploidies were used as outcome
      measures. RESULTS: The prevalence of microdeletions was 3.2% in unselected
      infertile men, 8.3% in men with nonobstructive azoospermia, and 5.5% in men with
      severe oligozoospermia. Only 2 of 99 deletions were found in men with more than 2
      million sperm/ml. No clinical data are useful to identify a priori patients with
      higher risk of Yq microdeletions. Most deletions are of the AZFc-b2/b4 subtype
      and are associated with variable spermatogenic phenotype, with sperm present in
      72% of the cases. Complete AZFa and AZFb (P5/Proximal P1) deletions are
      associated with Sertoli cell-only syndrome and alterations in spermatocyte
      maturation, respectively, whereas partial deletions in these regions are
      associated with milder phenotype and frequent presence of sperm. Men with AZFc
      b2/b4 deletions produce a higher percentage of sperm with nullisomy for the sex
      chromosomes and XY-disomy. CONCLUSIONS: This extensive clinical research expands
      the knowledge on genotype-phenotype relationships and confirms that the
      identification of Yq microdeletions has significant diagnostic and prognostic
      value, adding useful information for genetic counseling in these patients.

PMID- 17213278
TI  - Amylin and hypertension: association of an amylin -G132A gene mutation and
      hypertension in humans and amylin-induced endothelium dysfunction in rats.
AB  - CONTEXT: Amylin has been linked to the development of hypertension in several
      pathological states related to hypertension and insulin resistance, although
      there is scant data regarding its potential mechanisms of action. The -132 G/A
      mutation located within an activator domain of the amylin gene's promoter was
      first identified in a small cohort of Spanish patients with type 2 diabetes.
      OBJECTIVE: The objective of the study was to test the interference of amylin
      peptide with endothelium-dependent responses as an added potential mechanism for
      amylin-induced hypertension. DESIGN: A total of 384 patients with type 2 diabetes
      and 207 healthy controls were subjected to clinical analysis and genetic
      screening for the -132 G/A mutation of the amylin gene. The effect of amylin on
      endothelium-dependent responses was analyzed in aortic rings and mesenteric
      microvessels from nondiabetic rats. RESULTS: The prevalence of the mutation was
      10.1 vs. 0.9% in the control population (P<0.001). Hypertension was higher in a
      diabetic population carrying the mutation than in diabetic noncarriers (74 vs.
      57%; P<0.05). Diabetic carriers showed higher fasting amylin levels than diabetic
      noncarriers (11.4+/-7 vs. 8.2+/-3 pmol/liter; P<0.05). Preincubation with 20
      pmol/liter amylin impaired the relaxant responses induced by acetylcholine in rat
      aorta and mesenteric microvessels. This effect was abolished in both vascular
      beds in the presence of 100 micromol/liter NG-nitro-L-arginine methyl ester.
      CONCLUSIONS: We propose that amylin levels and hypertension may be linked by a
      novel mechanism involving the capacity of amylin to induce endothelial
      dysfunction by interfering with nitric oxide-mediated responses.

PMID- 17213279
TI  - Plasma adiponectin concentrations and risk of incident breast cancer.
AB  - INTRODUCTION: Previous retrospective case-control studies suggest that
      adiponectin, an obesity-related hormone, is inversely associated with breast
      cancer risk, particularly in postmenopausal women; however, no prospective
      studies exist. Therefore, we conducted a prospective case-control study nested
      within the Nurses' Health Study (NHS) and NHSII cohorts examining the association
      between plasma adiponectin concentrations and breast cancer risk. MATERIALS AND
      METHODS: Blood samples were collected from 1989 through 1990 (NHS) and 1996
      through 1999 (NHSII); adiponectin was measured by RIA. The analysis included 1477
      breast cancer cases diagnosed after blood collection and before June 2000 (NHS)
      or June 2003 (NHSII) who had one or two controls (n=2196) matched on age,
      menopausal status, postmenopausal hormone (PMH) use, fasting, and time of day and
      month of blood collection. We adjusted for body mass index at age 18, weight
      change from age 18 to blood draw, family history of breast cancer, history of
      benign breast disease, duration of PMH use, ages at menarche and first birth, and
      parity. RESULTS: Although we observed no association between adiponectin and
      breast cancer risk overall, there was a nearly significant interaction by
      menopausal status (P=0.08), with a relative risk, top vs. bottom quartile of 0.73
      (95% confidence interval, 0.55-0.98; P trend=0.08) among postmenopausal women and
      1.30 (95% confidence interval, 0.80-2.10; P trend=0.09) for premenopausal women.
      Among postmenopausal women, adiponectin appeared more strongly inversely
      associated in women who never used PMH (P heterogeneity=0.05) and women with low
      circulating estradiol levels (P heterogeneity=0.05). DISCUSSION: Our results
      suggest that adiponectin may be inversely associated with postmenopausal breast
      cancer risk, particularly in a low-estrogen environment.

PMID- 17213280
TI  - Adiponectin and resistin in human cerebrospinal fluid and expression of
      adiponectin receptors in the human hypothalamus.
AB  - CONTEXT: The adipokine leptin has critical importance in central appetite
      regulation. In contrast to some suggestion of adiponectin influencing energy
      homeostasis in rodents, there is no evidence for adiponectin or resistin entering
      the human blood-brain barrier. OBJECTIVE: The objective was to establish the
      presence of adiponectin or resistin in human cerebrospinal fluid (CSF) and to
      compare their distribution with leptin. Furthermore, we wished to examine the
      expression of the adiponectin receptors 1 and 2 (AdipR1, AdipR2) in the human
      hypothalamus. METHODS: For this purpose, serum and CSF samples were collected
      from 20 men and 19 women matched for age [men, 69.8 +/- 8.6 yr (mean +/- SD);
      women, 69.4 +/- 4.3 yr] and BMI (men, 29.4 +/- 3.4 kg/m(2); women, 27.3 +/- 4.8
      kg/m(2)) undergoing elective surgery under spinal anesthesia. RESULTS:
      Adiponectin was identified in CSF with levels 1000-fold less than serum, whereas
      resistin and leptin levels were 100-fold less. Unlike their serum levels,
      adiponectin CSF levels showed no gender difference or correlation with insulin
      resistance, which is similar to resistin CSF levels. The adiponectin and leptin
      CSF/serum ratios in our study exhibit the same pattern of gender-specific BMI
      association with inverse correlation in women (r = -0.61; P = 0.02) and no
      correlation in men (r = 0.026; P = not significant). Furthermore, immunostaining
      established AdipR1 and -2 in the hypothalamus and increased AdipR2 expression in
      the paraventricular nucleus, which is involved in energy regulation. CONCLUSION:
      In summary, our findings show both the presence of adiponectin and resistin in
      human CSF, with no effect of insulin resistance on CSF levels. The CSF entry of
      adiponectin and leptin in women appears to be impaired in obesity.

PMID- 17213281
TI  - Vitamin D receptor gene haplotype is associated with body height and bone size.
AB  - CONTEXT: Adult stature is a complex genetic trait. The vitamin D endocrine system
      has pleiotropic effects on several physiological processes, especially on
      skeletal metabolism. We recently identified promoter and 3'-untranslated region
      (UTR) haplotype alleles that influence vitamin D receptor (VDR) mRNA expression.
      OBJECTIVE: We studied whether VDR gene variants contribute to the genetic
      variation in height. DESIGN AND SUBJECTS: We studied VDR haplotype alleles and
      body height in two independent populations (n=7187). In a meta-analysis (n=14,157
      from 27 studies and our current data), we evaluated the effect of the Bsm I
      polymorphism. RESULTS: Haplotypes of the linkage disequilibrium block 3 and block
      5 were associated with body height differences with evidence for additive effects
      in the Rotterdam Study (P=0.00002) and the Longitudinal Aging Study Amsterdam
      study (P=0.001). Height differences between the extreme genotypes were 1.4 and
      2.7 cm, respectively. The relationship was independent of age, gender, presence
      of vertebral fractures, and age-related height loss. In the Rotterdam population,
      we found the combined genotype to be associated with decreased vertebral area
      (P=0.03) and femoral narrow neck width (P=0.002). In the meta-analysis, subjects
      with the "BB" genotype were 0.6 cm (95% confidence interval, 0.2-1.1 cm) taller
      than those with the "bb" genotype (P=0.006). CONCLUSION: VDR gene variants are
      associated with differences in body height as evidenced by our study and by a
      meta-analysis. It remains for further studies to confirm whether the underlying
      mechanism of the association involves lower VDR expression in cells important for
      determining bone size.

PMID- 17213282
TI  - Adult hypophosphatasia treated with teriparatide.
AB  - INTRODUCTION: Hypophosphatasia (HPP) features low serum alkaline phosphatase
      (ALP) activity (hypophosphatasemia) due to loss-of-function mutation within
      TNSALP, the gene that encodes "tissue-nonspecific" ALP (TNSALP). Consequently,
      inorganic pyrophosphate accumulates extracellularly and impairs skeletal
      mineralization. Affected adults manifest osteomalacia, often with slowly healing
      metatarsal stress fractures (MTSFs) and proximal femur pseudofractures.
      Pharmacotherapy remains elusive. PATIENT AND METHODS: A middle-aged woman
      sustained a slowly healing MTSF and then two enlarging MTSFs and a spontaneous
      proximal femur fracture. Pain persisted at all fracture sites. HPP was diagnosed
      as a result of low ALP activity (10-24 IU/liter; normal, 40-150 IU/liter) and
      elevated inorganic phosphate and pyridoxal 5'-phosphate concentrations in serum.
      Teriparatide (TPTD) (recombinant human PTH 1-34), 20 microg, was injected sc
      daily in an attempt to enhance osteoblast synthesis of TNSALP. RESULTS: Six weeks
      later, all fracture pain improved, and it resolved after 4 months. Radiographs of
      the enlarging MTSFs showed repair after 2-4 months. The femur fracture partially
      mended after 2 months and then healed. Additionally, hypophosphatasemia and
      hyperphosphatemia corrected, and biochemical markers of bone remodeling increased
      as long as TPTD (given for 18 months) was continued. The patient carried a
      heterozygous TNSALP missense mutation, p.D378V, which is common in the United
      States. CONCLUSION: This first HPP patient given TPTD demonstrated fracture
      repair accompanying correction of hypophosphatasemia and hyperphosphatemia and
      bone marker responses indicating enhanced skeletal remodeling. Increased TNSALP
      synthesis in bone together with lowered extracellular concentrations of inorganic
      phosphate (a competitive inhibitor of ALPs) seemed to improve her skeletal
      mineralization. Further evaluation of TPTD for HPP is warranted.

PMID- 17213283
TI  - Nilotinib exerts equipotent antiproliferative effects to imatinib and does not
      induce apoptosis in CD34+ CML cells.
AB  - Chronic myeloid leukemia (CML) stem and progenitor cells overexpress BcrAbl and
      are insensitive to imatinib mesylate (IM). We therefore investigated whether
      these cells were efficiently targeted by nilotinib. In K562, the inhibitory
      concentration (IC50) of nilotinib was 30 nM versus 600 nM for IM, consistent with
      its reported 20-fold-higher potency. However, in primary CD34(+) CML cells,
      nilotinib and IM were equipotent for inhibition of BcrAbl activity, producing
      equivalent but incomplete reduction in CrkL phosphorylation at 5 microM. CML
      CD34(+) cells were still able to expand over 72 hours with 5 microM of either
      drug, although there was a concentration-dependent restriction of amplification.
      As for IM, the most primitive cells (CFSE(max)) persisted and accumulated over 72
      hours with nilotinib and remained caspase-3 negative. Furthermore, nilotinib with
      IM led to further accumulation of this population, suggesting at least additive
      antiproliferative effects. These results confirmed that, like IM, the predominant
      effect of nilotinib is antiproliferative rather than proapoptotic.

PMID- 17213284
TI  - Involvement of Fyn kinase in Kit and integrin-mediated Rac activation,
      cytoskeletal reorganization, and chemotaxis of mast cells.
AB  - Kit receptor and its ligand stem cell factor (SCF) are critical regulators of
      mast cell production, proliferation, degranulation, and chemotaxis. In this
      study, we investigated how Fyn kinase regulates chemotaxis of mast cells toward
      SCF. On beta1-integrin engagement, Fyn-deficient (fyn(-/-)) mast cells displayed
      a striking defect in cell spreading and lamellipodia formation compared to wild
      type mast cells. The hematopoietic-specific Src family kinases (Lyn/Fgr/Hck) were
      not required for initial SCF-induced cell spreading. Reduced SCF-induced
      activation of Rac1 and Rac2 GTPases, p38 mitogen-activated protein kinase, and
      filamentous actin polymerization was observed in fyn(-/-) mast cells compared to
      wild-type mast cells. Retroviral-mediated expression of Fyn, constitutively
      active forms of Rac2 or phosphatidylinositol 3-kinase (PI3K) in fyn(-/-) mast
      cells rescued defects in SCF-induced cell polarization and chemotaxis of Fyn
      deficient mast cells. Thus, we conclude that Fyn kinase plays a unique role
      upstream of PI3K and Rac GTPases to promote the reorganization of the
      cytoskeleton during mast cell spreading and chemotaxis.

PMID- 17213285
TI  - Imatinib plus steroids induces complete remissions and prolonged survival in
      elderly Philadelphia chromosome-positive patients with acute lymphoblastic
      leukemia without additional chemotherapy: results of the Gruppo Italiano Malattie
      Ematologiche dell'Adulto (GIMEMA) LAL0201-B protocol.
AB  - Thirty elderly (> 60 years) Philadelphia chromosome-positive (Ph(+)) patients
      with acute lymphoblastic leukemia (ALL) received imatinib, 800 mg daily,
      associated to steroids without further chemotherapy as frontline treatment.
      Median age was 69 years (range, 61-83 years). Twenty-nine patients were evaluable
      for response and all of them obtained a hematologic complete remission, with a
      median BCR-ABL reduction of 2.9 and 2.0 logs in p190(+) and p210(+) cases,
      respectively. Most of the induction treatment did not require admission of the
      patients. No major toxicities occurred and the treatment was well tolerated.
      Median survival from diagnosis was 20 months. This study shows that elderly Ph(+)
      patients with ALL-often considered eligible only for palliative treatment
      strategies-may benefit from an imatinib-steroids protocol, which does not require
      chemotherapy nor a long hospitalization, is feasible, highly active, and
      associated with a good quality of life.

PMID- 17213286
TI  - Keratinocyte growth factor (KGF) enhances postnatal T-cell development via
      enhancements in proliferation and function of thymic epithelial cells.
AB  - The systemic administration of keratinocyte growth factor (KGF) enhances T-cell
      lymphopoiesis in normal mice and mice that received a bone marrow transplant. KGF
      exerts protection to thymic stromal cells from cytoablative conditioning and
      graft-versus-host disease-induced injury. However, little is known regarding
      KGF's molecular and cellular mechanisms of action on thymic stromal cells. Here,
      we report that KGF induces in vivo a transient expansion of both mature and
      immature thymic epithelial cells (TECs) and promotes the differentiation of the
      latter type of cells. The increased TEC numbers return within 2 weeks to normal
      values and the microenvironment displays a normal architectural organization.
      Stromal changes initiate an expansion of immature thymocytes and permit regular T
      cell development at an increased rate and for an extended period of time. KGF
      signaling in TECs activates both the p53 and NF-kappaB pathways and results in
      the transcription of several target genes necessary for TEC function and T-cell
      development, including bone morphogenetic protein 2 (BMP2), BMP4, Wnt5b, and
      Wnt10b. Signaling via the canonical BMP pathway is critical for the KGF effects.
      Taken together, these data provide new insights into the mechanism(s) of action
      of exogenous KGF on TEC function and thymopoiesis.

PMID- 17213287
TI  - Enhanced T-cell reconstitution by hematopoietic progenitors expanded ex vivo
      using the Notch ligand Delta1.
AB  - A physiologic role for Notch signaling in hematopoiesis has been clearly defined
      in lymphoid differentiation, with evidence suggesting a critical role in T-cell
      versus B-cell fate decisions. Previously, we demonstrated that activation of
      endogenous Notch receptors by culture of murine lin(-)Sca-1(+)c-kit(+) (LSK)
      hematopoietic progenitors with exogenously presented Notch ligand, Delta1(ext
      IgG), consisting of the extracellular domain of Delta1 fused to the Fc domain of
      human IgG(1), promoted early T-cell differentiation and increased the number of
      progenitors capable of short-term lymphoid and myeloid reconstitution. Here we
      show that culture of LSK precursors with Delta1(ext-IgG) increases the number of
      progenitors that are able to rapidly repopulate the thymus and accelerate early T
      cell reconstitution with a diversified T-cell receptor repertoire. Most of the
      early T-cell reconstitution originated from cells that expressed lymphoid
      associated antigens: B220, Thy1, CD25, and/or IL7Ralpha, whereas the most
      efficient thymic repopulation on a per cell basis originated from the smaller
      number of cultured cells that did not express lymphoid-associated antigens. These
      findings demonstrate the potential of Delta1(ext-IgG)-cultured cells for
      accelerating early immune reconstitution after hematopoietic cell
      transplantation.

PMID- 17213288
TI  - Progression to end-stage liver disease in patients with inherited bleeding
      disorders and hepatitis C: an international, multicenter cohort study.
AB  - Prior to 1990, many patients with inherited bleeding disorders were infected with
      hepatitis C virus (HCV). This study assessed the risk of end-stage liver disease
      (ESLD) in patients with hemophilia with chronic hepatitis C. Patients were
      infected between 1961 and 1990 and were followed up to August 2005. Of 847 anti
      HCV(+) patients, 160 (19%) spontaneously cleared HCV and 687 (81%) developed
      chronic hepatitis C. Coinfection with HIV was present in 210 patients. After 35
      years of infection the cumulative incidence of ESLD was 11.5% (95% CI, 8.2%
      14.8%) in HIV(-) patients and 35.1% (95% CI, 29.2%-41.0%; P < .001) in patients
      coinfected with HIV. Independent risk factors of ESLD were HIV coinfection
      (hazard ratio 13.8; 95% CI, 7.5-25.3), older age at infection (hazard ratio 2.3
      per 10 years; 95% CI, 2.0-2.8), alcohol abuse (hazard ratio 4.9; 95% CI, 2.5
      9.6), and presence of HCV genotype 1 (hazard ratio 2.2; 95% CI, 1.1-4.2). With
      longer duration of HCV infection, the risk of developing ESLD is emerging in
      patients with inherited bleeding disorders. Risk factors for rapid progression to
      ESLD are alcohol abuse, coinfection with HIV, older age at infection, and
      presence of HCV genotype 1.

PMID- 17213289
TI  - Targeting aurora kinases as therapy in multiple myeloma.
AB  - The aurora kinases facilitate transit from G2 through cytokinesis and, thus, are
      targets in cancer therapy. Multiple myeloma (MM) is a malignancy characterized by
      genetic instability, suggesting a disruption of checkpoints that arrest cells at
      G2M when injury to the mitotic machinery occurs. Since deficient checkpoints
      would prevent cell cycle arrest and may render cells susceptible to apoptosis in
      mitosis and since aurora kinases are intermediaries in checkpoint pathways, we
      tested antimyeloma effects of 2 agents that inhibit aurora kinases. Both
      inhibited growth of MM lines and primary myeloma samples at nanomolar
      concentrations while having less of an effect on proliferating lymphocytes and
      hematopoietic cells. MM cells were not protected by IL-6 or activating mutations
      of Ras. Antimyeloma effects included induction of tetraploidy followed by
      apoptosis. Apoptosis correlated with inhibition of aurora activity as shown by
      reduction of histone 3B phosphorylation. Ectopic expression of aurora A protected
      MM cells against aurora inhibitors but had no effect on apoptosis induced by
      bortezomib. As expression of RHAMM in MM contributes to genetic instability, we
      tested effects of RHAMM. RHAMM overexpression enhanced sensitivity to apoptosis
      and RHAMM silencing decreased sensitivity. These results suggest potential for
      aurora kinase inhibitors in MM especially in patients in whom RHAMM is
      overexpressed.

PMID- 17213290
TI  - Donor T-cell alloreactivity against host thymic epithelium limits T-cell
      development after bone marrow transplantation.
AB  - Acute graft-versus-host disease (aGVHD) impairs thymus-dependent T-cell
      regeneration in recipients of allogeneic bone marrow transplants through yet to
      be defined mechanisms. Here, we demonstrate in mice that MHC-mismatched donor T
      cells home into the thymus of unconditioned recipients. There, activated donor T
      cells secrete IFN-gamma, which in turn stimulates the programmed cell death of
      thymic epithelial cells (TECs). Because TECs themselves are competent and
      sufficient to prime naive allospecific T cells and to elicit their effector
      function, the elimination of host-type professional antigen-presenting cells
      (APCs) does not prevent donor T-cell activation and TEC apoptosis, thus
      precluding normal thymopoiesis in transplant recipients. Hence, strategies that
      protect TECs may be necessary to improve immune reconstitution following
      allogeneic bone marrow transplantation.

PMID- 17213291
TI  - FcRL6, a new ITIM-bearing receptor on cytolytic cells, is broadly expressed by
      lymphocytes following HIV-1 infection.
AB  - Fc receptor-like proteins (FcRLs) are a growing family of molecules homologous to
      FcgammaRI. Whereas all 7 previously reported Fc receptor homologs are expressed
      by B cells, here we report a new receptor, FcRL6, that is expressed by cytolytic
      cells including natural killer (NK) cells and effector and effector-memory CD8(+)
      T cells. FcRL6 contains a novel cytoplasmic cysteine-rich motif and recruits SHP
      2 through a phosphorylated ITIM, indicating a potential signaling function in
      effector lymphocytes. In vitro, FcRL6 does not greatly influence NK-cell or
      CD8(+) T-cell-mediated cytotoxicity and has minimal impact on cytokine secretion.
      However, FcRL6 expression among T lymphocytes is greatly expanded in human
      immunodeficiency virus type 1 (HIV-1)-infected individuals, and includes not only
      effector and effector-memory CD8(+) T cells but also populations of CD4(+) T
      cells. Expansion of FcRL6-positive lymphocytes is not related to viral load, but
      is indicative of the dysregulated expansion of terminally differentiated effector
      lymphocyte populations in response to chronic HIV-1 infection and may serve as an
      important marker for chronic immune activation and for tracking the generation of
      effector cells following immune stimulation.

PMID- 17213292
TI  - Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA
      identical sibling stem cell transplantation in first remission acute myeloid
      leukemia in young and middle-aged adults: benefits for whom?
AB  - The Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for
      Clinical Cancer Research (HOVON-SAKK) collaborative study group evaluated outcome
      of patients (pts) with acute myeloid leukemia (AML) in first remission (CR1)
      entered in 3 consecutive studies according to a donor versus no-donor comparison.
      Between 1987 and 2004, 2287 pts were entered in these studies of whom 1032 pts
      (45%) without FAB M3 or t(15;17) were in CR1 after 2 cycles of chemotherapy,
      received consolidation treatment, and were younger than 55 years of age and
      therefore eligible for allogeneic hematopoietic stem cell transplantation (allo
      SCT). An HLA-identical sibling donor was available for 326 pts (32%), whereas 599
      pts (58%) lacked such a donor, and information was not available in 107 pts.
      Compliance with allo-SCT was 82% (268 of 326). Cumulative incidences of relapse
      were, respectively, 32% versus 59% for pts with versus those without a donor (P <
      .001). Despite more treatment-related mortality (TRM) in the donor group (21%
      versus 4%, P < .001), disease-free survival (DFS) appeared significantly better
      in the donor group (48% +/- 3% versus 37% +/- 2% in the no-donor group, P <
      .001). Following risk-group analysis, DFS was significantly better for pts with a
      donor and an intermediate- (P = .01) or poor-risk profile (P = .003) and also
      better in pts younger than 40 years of age (P < .001). We evaluated our results
      and those of the previous MRC, BGMT, and EORTC studies in a meta-analysis, which
      revealed a significant benefit of 12% in overall survival (OS) by donor
      availability for all patients with AML in CR1 without a favorable cytogenetic
      profile.

PMID- 17213293
TI  - Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq
      in human platelets.
AB  - Retinoid X receptors (RXRs) are important transcriptional nuclear hormone
      receptors, acting as either homodimers or the binding partner for at least one
      fourth of all the known human nuclear receptors. Functional nongenomic effects of
      nuclear receptors are poorly understood; however, recently peroxisome
      proliferator-activated receptor (PPAR) gamma, PPARbeta, and the glucocorticoid
      receptor have all been found active in human platelets. Human platelets express
      RXRalpha and RXRbeta. RXR ligands inhibit platelet aggregation and TXA(2) release
      to ADP and the TXA(2) receptors, but only weakly to collagen. ADP and TXA(2) both
      signal via the G protein, Gq. RXR rapidly binds Gq but not Gi/z/o/t/gust in a
      ligand-dependent manner and inhibits Gq-induced Rac activation and intracellular
      calcium release. We propose that RXR ligands may have beneficial clinical actions
      through inhibition of platelet activation. Furthermore, our results demonstrate a
      novel nongenomic mode for nuclear receptor action and a functional cross-talk
      between G-protein and nuclear receptor signaling families.

PMID- 17213294
TI  - Validity of a stage of change instrument in assessing medication adherence in
      indigent patients with HIV infection.
AB  - BACKGROUND: Adherence to antiretroviral therapy (ART) is vital to achieve durable
      suppression of viral replication. Effective mechanisms to predict adherence can
      be difficult to implement in clinical practice settings. Self-administered
      questionnaires are a practical option for assessing patient adherence but may
      lack validation with objective measures of adherence. OBJECTIVE: To examine the
      ability of a 2 item stage of change (SOC) questionnaire to predict medication
      adherence in indigent patients receiving ART. METHODS: Patients participating in
      an ongoing study to examine adherence interventions were administered a 2 item
      SOC instrument to assess readiness for adherence behavior. The SOC instrument was
      given to patients prior to beginning ART and readministered after they had
      received 16 weeks of treatment. Electronic monitoring was used to examine the
      validity of the SOC instrument to predict patient readiness for adherence
      behavior. RESULTS: Thirty-one patients completed the SOC questionnaire prior to
      beginning a new ART regimen. Most (87%) patients were male, had previously
      received antiretroviral therapy (77%), and had an AIDS diagnosis (77%). The SOC
      category determined at baseline was a poor predictor of adherence at 4 and 16
      weeks; however, the SOC category determined after treatment onset (week 16) was a
      strong predictor of adherence at both time points (p < 0.001 for 4 and 16 weeks;
      one way ANOVA). CONCLUSIONS: The SOC category determined at baseline correlated
      poorly with subsequent medication adherence in our indigent, HIV-infected patient
      population. Prediction of adherence based on SOC after treatment initiation may
      provide a better estimate of adherence behavior. Recognition of this limitation
      may help clinicians more accurately interpret predicted adherence behavior from
      self-report instruments.

PMID- 17213295
TI  - Etomidate use for Cushing's syndrome caused by an ectopic adrenocorticotropic
      hormone-producing tumor.
AB  - OBJECTIVE: To report the preparation and use of etomidate in a patient with
      Cushing's syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)
      producing tumor. CASE SUMMARY: A 73-year-old man with a 5 year history of
      prostate cancer was admitted for symptoms consistent with Cushing's syndrome. He
      was started on oral metyrapone for elevated serum cortisol, ACTH, and 24 hour
      urinary unbound cortisol levels. Shortly after starting metyrapone, he was
      transferred to the medical intensive care unit for new-onset atrial fibrillation,
      neutropenic fever, and respiratory failure. A nasogastric tube could not be
      inserted to administer metyrapone. Intravenous etomidate 4 mg/h (0.06 mg/kg/h)
      was initiated to decrease cortisol production and provide sedation for mechanical
      ventilation. Despite supportive treatment, the patient died from multiple organ
      dysfunction. DISCUSSION: For patients exhibiting signs and symptoms of Cushing's
      syndrome who have no enteral access, administering etomidate intravenously may be
      a viable alternative treatment route. Although several articles report the use of
      etomidate to control cortisol overproduction, the intravenous preparation and
      stability are discussed only vaguely. In our patient, etomidate was infused via a
      30 mL syringe, 2 mg/mL undiluted through a central venous catheter; syringe use
      was limited to 24 hours. Etomidate should be infused only with continuous
      monitoring of hemodynamics and periodic assessment of adrenal function.
      CONCLUSIONS: When oral or enteral medications cannot be administered and sedation
      is required in critically ill patients, etomidate is an appropriate intravenous
      agent for hypercortisolemia. There were no obvious problems with stability when
      undiluted etomidate 2 mg/mL was infused through a dedicated central venous
      catheter lumen.

PMID- 17213296
TI  - Rotigotine: transdermal dopamine agonist treatment of Parkinson's disease and
      restless legs syndrome.
AB  - OBJECTIVE: To evaluate the pharmacology, pharmacokinetics, clinical efficacy, and
      tolerability of rotigotine, a nonergoline D(3)/D(2)/D(1) dopamine receptor
      agonist in the treatment of Parkinson's disease and restless legs syndrome (RLS).
      DATA SOURCES: A literature search was conducted using MEDLINE (1996-December
      2006) and International Pharmaceutical Abstracts, using the search terms
      rotigotine and dopamine agonist. References cited in the articles were reviewed
      for additional information. Information was also obtained from Schwarz Pharma.
      Abstracts for posters at scientific conferences were accessed from conference Web
      sites. STUDY SELECTION AND DATA EXTRACTION: English-language literature reporting
      controlled animal and human clinical studies was reviewed to evaluate the
      pharmacology, pharmacokinetics, therapeutic use, and adverse effects of
      rotigotine. Clinical trials selected for inclusion were limited to those with
      human subjects; data from animal studies were included if human data were not
      available. DATA SYNTHESIS: Rotigotine has been investigated in early Parkinson's
      disease, as adjuvant therapy to levodopa in advanced Parkinson's disease, and in
      RLS. It is administered transdermally, which provides the convenience of once
      daily dosing, constant drug delivery, and sustained stable plasma concentrations.
      In clinical trials of patients with early Parkinson's disease, rotigotine has
      decreased combined scores on the motor and activities of daily living sections of
      the Unified Parkinson's Disease Rating Scale up to 85 weeks. In patients with
      advanced Parkinson's disease, rotigotine reduced mean off-time when used as an
      adjuvant to levodopa. Rotigotine has decreased the severity of RLS in Phase III
      trials. Acute adverse events are similar to those of other dopamine agonists and
      are most common during the titration phase. Mild-to-moderate application site
      reactions are common. CONCLUSIONS: Longer trials are required to determine
      whether transdermal rotigotine will reduce development of dyskinesias and motor
      fluctuations in Parkinson's disease and augmentation and rebound in RLS by
      preventing pulsatile dopamine stimulation associated with levodopa and other
      dopamine agonists.

PMID- 17213297
TI  - Embolisation of proximal anastomotic pseudoaneurysm developing after surgical
      repair of abdominal aortic aneurysm with a bifurcated graft with n-butyl
      cyanoacrylate.
AB  - We report a 60-year-old man who after undergoing surgical repair of an abdominal
      aortic aneurysm with a bifurcated graft subsequently developed a proximal
      anastomotic pseudoaneurysm, which was successfully treated by embolisation with n
      butyl cyanoacrylate.

PMID- 17213298
TI  - Significant response of radiation induced CNS toxicity to high dose steroid
      administration.
AB  - Treatment of radiation myelopathy remains a challenge. Supportive and
      rehabilitative therapy is the mainstay of treatment. This article describes a
      case of central nervous system (CNS) toxicity of radiation with a progressive
      improvement in the clinicoradiological picture following high dose steroid
      treatment. A female patient was admitted to the neurology department of our
      hospital 7 months after a course of radiotherapy in another centre for lingual
      epidermoid cancer. Neurological examination revealed a heavy spastic quadriplegia
      syndrome. On MRI examination, T2 weighted hyperintensities were observed in
      cerebral and cerebellar peduncles, periventricular regions and medulla spinalis
      at Th1-Th2 levels. The patient was treated with high dose methylprednisolone, 1 g
      day(-1) for 5 days (pulse therapy) followed by oral methylprednisolone 80 mg day(
      1) for a week, tapered over 3 weeks. Within the first week of pulse therapy, she
      regained muscle strength of upper limbs against gravity. At the 2 year follow-up,
      MRI demonstrated obvious regression of the lesions in the medulla and cerebellum
      with disappearance of contrast enhancement. This case report is notable with the
      complete disappearance of MRI lesions at the 2 year follow-up after the treatment
      with high dose steroid.

PMID- 17213299
TI  - Comprehensive multidetector CT assessment of apical hypertrophic cardiomyopathy.
AB  - 16-slice multidetector CT (MDCT) cardiac findings of a middle-aged man with known
      apical hypertrophic cardiomyopathy (AHC) and recent atypical chest pain are
      presented. MDCT enabled comprehensive evaluation of the coronary arteries,
      diagnosing myocardial bridging of the left anterior descending (LAD) and first
      diagonal arteries. It also enabled dynamic evaluation of myocardial thickness and
      left ventricular global and regional function. This case illustrates the full
      capabilities of MDCT in the evaluation of AHC.

PMID- 17213300
TI  - MRI appearances of pelvic malakoplakia.
AB  - We report the MRI appearances in a patient with parametrial malakoplakia. The
      patient complained of pelvic pain and vaginal discharge. Physical examination
      revealed a "frozen" pelvis suggestive of malignancy. MRI showed bilateral
      parametrial "infiltration", but no overt primary pelvic tumour. The combination
      of these findings together with the inflammatory symptoms suggested an
      inflammatory condition. Malakoplakia was confirmed at resective biopsy.

PMID- 17213301
TI  - A case of torted parafimbrial cyst on MRI: case report and review of the
      literature.
AB  - Para-ovarian cysts (POCs) are an occasional finding at surgery, although they are
      rarely appreciated on imaging studies. Accurate diagnosis depends upon the
      demonstration of a para-ovarian location. We present the MR appearances of a
      torted POC in a fimbrial location, resembling a dermoid cyst.

PMID- 17213302
TI  - National survey of doses from CT in the UK: 2003.
AB  - A review of patient doses from CT examinations in the UK for 2003 has been
      conducted on the basis of data received from over a quarter of all UK scanners,
      of which 37% had multislice capability. Questionnaires were employed to collect
      scan details both for the standard protocols established at each scanner for 12
      common types of CT examination on adults and children, and for samples of
      individual patients. This information was combined with published scanner
      specific CT dose index (CTDI) coefficients to estimate values of the standard
      dose indices CTDI(w) and CTDI(vol) for each scan sequence. Knowledge of each scan
      length allowed assessment of the dose-length product (DLP) for each examination,
      from which effective doses were then estimated. When compared with a previous UK
      survey for 1991, wide variations were still apparent between CT centres in the
      doses for standard protocols. The mean UK doses for adult patients were in
      general lower by up to 50% than those for 1991, although doses were slightly
      higher for multislice (4+) (MSCT) relative to single slice (SSCT) scanners.
      Values of CTDI(vol) for MSCT were broadly similar to European survey data for
      2001. The third quartile values of these dose distributions have been used to
      derive UK national reference doses for examinations on adults (separately for
      SSCT and MSCT) and children as initial tools for promoting patient protection.
      The survey has established the PREDICT (Patient Radiation Exposure and Dose in
      CT) database as a sustainable national resource for monitoring dose trends in CT
      through the ongoing collation of further survey data.

PMID- 17213303
TI  - Optimal beam quality selection in digital mammography.
AB  - An experimental method of determining the optimal beam quality for digital
      mammography systems was applied to two systems (Fuji Profect and GE Senographe
      2000D). The mean glandular dose (MGD) and contrast-to-noise ratio (CNR) were
      measured using Perspex breast phantoms simulating breasts from 20 mm to 90 mm
      thick. For each thickness, four combinations of tube voltage and target/filter
      were tested. Optimal beam quality was defined as giving a target CNR for the
      lowest MGD and was similar for the two systems. For breasts with a thickness of
      21 mm or 32 mm, a tube voltage of either 25 kV or 28 kV and a Mo/Mo target/filter
      combination was optimal. For breast thicknesses of 45 mm and greater, the
      combination that had the highest X-ray energy (34 kV Rh/Rh) was optimal.
      Optimization using the higher energy beam quality required greater detector dose
      to compensate for the lower contrast. Thus for a 75 mm thick breast the 34 kV
      Rh/Rh combination required about a 90% greater detector dose than 28 kV Mo/Mo to
      achieve the same CNR because of the 25% reduction in contrast. Nonetheless, the
      MGD was reduced by 32% by choosing the higher energy spectra and achieving the
      same CNR. Current automatic exposure control (AEC) designs that aim for a fixed
      detector dose are not optimal and greater use of higher energy spectra should be
      accompanied by higher detector doses at all breast thicknesses which are average
      or above. This may result in slightly higher doses, but better image quality for
      these breasts.

PMID- 17213304
TI  - A red eye.

PMID- 17213305
TI  - MRI histopathology correlation of N-phenylanthranilic acid induced nephropathy in
      rats.

PMID- 17213306
TI  - Nonpeptidic glucagon-like peptide 1 receptor agonists: a magic bullet for
      diabetes?

PMID- 17213307
TI  - Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex.
AB  - The Sir2 histone deacetylases are important for gene regulation, metabolism, and
      longevity. A unique feature of these enzymes is their utilization of NAD(+) as a
      cosubstrate, which has led to the suggestion that Sir2 activity reflects the
      cellular energy state. We show that SIRT1, a mammalian Sir2 homologue, is also
      controlled at the transcriptional level through a mechanism that is specific for
      this isoform. Treatment with the glycolytic blocker 2-deoxyglucose (2-DG)
      decreases association of the redox sensor CtBP with HIC1, an inhibitor of SIRT1
      transcription. We propose that the reduction in transcriptional repression
      mediated by HIC1, due to the decrease of CtBP binding, increases SIRT1
      expression. This mechanism allows the specific regulation of SIRT1 in response to
      nutrient deprivation.

PMID- 17213308
TI  - A blasticidin S-resistant Plasmodium falciparum mutant with a defective
      plasmodial surface anion channel.
AB  - Erythrocytes infected with malaria parasites exhibit marked increases in
      permeability to organic and inorganic solutes. The plasmodial surface anion
      channel (PSAC), an unusual voltage-dependent ion channel induced on the host
      membrane after infection, may play a central role in these permeability changes.
      Here, we identified a functional PSAC mutant through in vitro selection with
      blasticidin S. Resistance to blasticidin S was generated during culture and
      correlated with significant reductions in permeability to multiple solutes,
      consistent with uptake via a common pathway. Single channel recordings revealed
      marked changes in PSAC gating with the addition of a subconductance state not
      present in wild-type channels. The channel's selectivity profile and pharmacology
      also were significantly altered. Eventual loss of the mutant phenotype upon
      removal of selective pressure and slower growth of mutant parasites suggest that
      PSAC serves an important role in intracellular parasite survival. These findings
      provide solid evidence for the uptake of diverse solutes via PSAC and implicate
      one or more parasite genes in expression of this channel.

PMID- 17213309
TI  - WIP is a chaperone for Wiskott-Aldrich syndrome protein (WASP).
AB  - Wiskott-Aldrich syndrome protein (WASP) is in a complex with WASP-interacting
      protein (WIP). WASP levels, but not mRNA levels, were severely diminished in T
      cells from WIP(-/-) mice and were increased by introduction of WIP in these
      cells. The WASP binding domain of WIP was shown to protect WASP from degradation
      by calpain in vitro. Treatment with the proteasome inhibitors MG132 and
      bortezomib increased WASP levels in T cells from WIP(-/-) mice and in T and B
      lymphocytes from two WAS patients with missense mutations (R86H and T45M) that
      disrupt WIP binding. The calpain inhibitor calpeptin increased WASP levels in
      activated T and B cells from the WASP patients, but not in primary T cells from
      the patients or from WIP(-/-) mice. Despite its ability to increase WASP levels
      proteasome inhibition did not correct the impaired IL-2 gene expression and low F
      actin content in T cells from the R86H WAS patient. These results demonstrate
      that WIP stabilizes WASP and suggest that it may also be important for its
      function.

PMID- 17213310
TI  - In the regulation of cytochrome P450 genes, phenobarbital targets LKB1 for
      necessary activation of AMP-activated protein kinase.
AB  - Transcriptional activation of cytochrome P450 (CYP) genes and various drug
      metabolizing enzymes by the prototypical inducer phenobarbital (PB) and many
      other drugs and chemicals is an adaptive response of the organism to exposure to
      xenobiotics. The response to PB is mediated by the nuclear receptor constitutive
      androstane receptor (CAR), whereas the chicken xenobiotic receptor (CXR) has been
      characterized as the PB mediator in chicken hepatocytes. Our previous results
      suggested an involvement of AMP-activated protein kinase (AMPK) in the molecular
      mechanism of PB induction. Here, we show that the mechanism of AMPK activation is
      related to an effect of PB-type inducers on mitochondrial function with
      consequent formation of reactive oxygen species (ROS) and phosphorylation of AMPK
      by the upstream kinase LKB1. Gain- and loss-of-function experiments demonstrate
      that LKB1-activated AMPK is necessary in the mechanism of drug induction and that
      this is an evolutionary conserved pathway for detoxification of exogenous and
      endogenous chemicals. The activation of LKB1 adds a proximal target to the so far
      elusive sequence of events by which PB and other drugs induce the transcription
      of multiple genes.

PMID- 17213311
TI  - A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in
      diabetic db/db mice.
AB  - Peptidic mimics of the gut hormone glucagon-like peptide (GLP) 1, exemplified by
      the recently approved drug exenatide, show promise as therapies for type 2
      diabetes. Such "incretin mimetics" regulate glucose appearance in the plasma and
      can restore glucose-stimulated insulin secretion without excess risk of
      hypoglycemia. The need for injection, which may limit the use of peptidic GLP-1
      receptor (GLP-1R) agonists, has driven largely unsuccessful efforts to find
      smaller molecules. The failure to identify orally effective agonists has instead
      promoted the indirect approach of inhibiting the GLP-1-degrading enzyme
      dipeptidyl peptidase IV. Here we report a nonpeptidic GLP-1R agonist with
      sufficient activity to evoke effects in whole animals, including antidiabetic
      efficacy in db/db mice. Two substituted cyclobutanes (S4P and Boc5) were
      developed after screening a compound library against a cell line stably
      cotransfected with GLP-1R and a cAMP-responsive reporter. Each bound to GLP-1R
      and increased intracellular cAMP. Agonist effects were blocked by the GLP-1R
      antagonist exendin(9-39). Boc5 amplified glucose-stimulated insulin secretion in
      isolated rat islets. Both i.p. and oral administration of Boc5 dose-dependently
      inhibited food intake in mice, an effect that could be blocked by pretreatment
      with exendin(9-39). Daily injections of Boc5 into db/db mice reduced HbA1c to
      nondiabetic values, an effect not observed in ad libitum-fed or pair-fed diabetic
      controls. Thus, Boc5 behaved as a full GLP-1 mimetic in vitro and in vivo. The
      chemical genus represented by Boc5 may prompt the exploration of orally available
      GLP-1R agonists with potential utility in diabetes and obesity.

PMID- 17213312
TI  - Further evidence that Whorfian effects are stronger in the right visual field
      than the left.
AB  - The Whorf hypothesis holds that differences between languages induce differences
      in perception and/or cognition in their speakers. Much of the experimental work
      pursuing this idea has focused on the domain of color and has centered on the
      issue of whether linguistically coded color categories influence color
      discrimination. A new perspective has been cast on the debate by recent results
      that suggest that language influences color discrimination strongly in the right
      visual field but not in the left visual field (LVF). This asymmetry is likely
      related to the contralateral projection of visual fields to cerebral hemispheres
      and the specialization of the left hemisphere for language. The current study
      presents three independent experiments that replicate and extend these earlier
      results by using different tasks and testing across different color category
      boundaries. Our results differ in one respect: although we find that Whorfian
      effects on color are stronger for stimuli in the right visual field than in the
      LVF, we find that there are significant category effects in the LVF as well. The
      origin of the significant category effect in the LVF is considered, and two
      factors that might account for the pattern of results are proposed.

PMID- 17213313
TI  - The unique insert at the end of the myosin VI motor is the sole determinant of
      directionality.
AB  - Myosin VI moves toward the pointed (minus) end of actin filaments, the reverse
      direction of other myosin classes. The myosin VI structure demonstrates that a
      unique insert at the end of the motor repositions its lever arm and is at least
      in part responsible for the reversal of directionality. However, it has been
      proposed that there must be additional modifications within the motor that
      contribute to its large step size and to the reversal of directionality. To
      ascertain the inherent directionality of the motor core, we attached the myosin V
      lever arm to myosin VI, with and without the unique insert. If the insert was
      maintained, the motor moved toward the minus end of actin filaments, but if
      removed, movement was redirected toward the plus end. Single-molecule studies
      revealed that further adaptations within the motor increase the magnitude and
      variability of the plus-end directed converter movements, and unexpectedly
      provide the source of the highly variable myosin VI step size. Thus, the unique
      insert is necessary and sufficient to reverse an inherently plus-end directed
      myosin.

PMID- 17213314
TI  - Gas-phase ions of solute species from charged droplets of solutions.
AB  - Charged droplets, produced by electrostatic dispersion of solutions of amino
      acids and peptides are driven by a potential difference a countercurrent to a
      flow of heated nitrogen bath gas. Evaporation of solvent from those droplets
      increases surface charge density, resulting in subdivision into smaller charged
      droplets. Each smaller droplet repeats that sequence until the ultimate result is
      a dispersion of solvent-free solute ions in the bath gas. Surprisingly, mass
      spectrometric analyses of the final ion-bath gas mixtures showed that the
      relative abundances of the desolvated ions were substantially higher when the
      nitrogen bath gas contained vapor of a polar solvent species than when no such
      solvent vapor was present. Adding solvent vapor to the background bath gas can
      certainly not increase, but must decrease, the net rate of solvent evaporation
      from the charged droplets. Consequently, the observed enhancement of ion
      formation by the presence of solvent vapor in the bath gas constitutes persuasive
      evidence that the observed solute ions cannot have been produced by the charged
      residue mechanism originally suggested by Dole et al. [Dole M, et al. (1968) J
      Chem Phys 49:2240-2249 and Dole M, Rheude A, Mack LL (1970) J Chem Phys 52:4977
      4986]. It is therefore concluded that electrospray ions are most likely produced
      by the ion evaporation mechanism of Iribarne and Thomson [Iribarne JV, Thomson BA
      (1975) J Chem Phys 64:2287-2294]. Moreover, and probably as important, this
      observed signal enhancement constitutes a welcome increase in detection
      sensitivity.

PMID- 17213315
TI  - On positivity of certain systems of partial differential equations.
AB  - We extend the Fefferman-Phong inequality to N x N systems of PDEs with symbol
      p(x, xi) = A(x)e(xi) + B(x, xi) + C(x) = p(x, xi)* > or = -cl, (x, xi)[abstract:
      see text] where e is a positive homogeneous quadratic form, and B(x, xi) =
      Sigma(l=1)(n) B(l)(x)xi(l). We thus generalize a result by L.-Y. Sung that was
      obtained for systems of ordinary differential equations. Our proof exploits a
      Calderon-Zygmund decomposition of the phase-space )[abstract: see text] of the
      kind introduced by C. Fefferman and D. H. Phong for studying subelliptic
      differential operators and goes by induction on the size N of the system.

PMID- 17213316
TI  - Plants and people from the Early Neolithic to Shang periods in North China.
AB  - An assemblage of charred plant remains collected from 26 sites in the Yiluo
      valley of North China as part of an archaeological survey spans the period from
      the sixth millennium to 1300 calibrated calendrical years (cal) B.C. The plant
      remains document a long sequence of crops, weeds, and other plants in the
      country. The results also demonstrate the effectiveness of sediment sampling as
      part of an archaeological survey. Ten accelerator mass spectrometer (AMS)
      radiocarbon dates on crop remains inform an assessment of the sequence of
      agricultural development in the region. Foxtail millet (Setaria italica subsp.
      italica) was grown during the Early Neolithic period and was the principal crop
      for at least four millennia. Broomcorn millet (Panicum miliaceum) was
      significantly less important throughout the sequence. Rice (Oryza sativa) was
      introduced by 3000 cal B.C. but apparently was not an important local crop. Wheat
      became a significant crop between 1600 and 1300 cal B.C. The weed flora
      diversified through time and were dominated by annual grasses, some of which were
      probably fodder for domesticated animals. The North China farming tradition that
      emphasized dry crops (millets, wheat, and legumes) with some rice appears to have
      been established at the latest by the Early Shang (Erligang; 1600-1300 B.C.)
      period.

PMID- 17213317
TI  - Instant effect of soluble antigen on effector T cells in peripheral immune organs
      during immunotherapy of autoimmune encephalomyelitis.
AB  - i.v. infusion of native autoantigen or its altered peptide variants is an
      important therapeutic option for the treatment of autoimmune diseases, because it
      selectively targets the disease-inducing T cells. To learn more about the
      mechanisms and kinetics of this approach, we visualized the crucial initial
      effects of i.v. infusion of peptides or intact protein on GFP-tagged
      autoaggressive CD4(+) effector T cells using live-video and two-photon in situ
      imaging of spleens in living animals. We found that the time interval between
      i.v. injection of intact protein to first changes in T cell behavior was
      extremely short; within 10 min after protein application, the motility of the T
      cells changed drastically. They slowed down and became tethered to local sessile
      stromal cells. A part of the cells aggregated to form clusters. Within the
      following 20 min, IFN-gamma mRNA was massively (>100-fold) up-regulated; surface
      IL-2 receptor and OX-40 (CD 134) increased 1.5 h later. These processes depleted
      autoimmune T cells in the blood circulation, trapping the cells in the peripheral
      lymphoid organs and thus preventing them from invading the CNS. This specific
      blockage almost completely abrogated CNS inflammation and clinical disease. These
      findings highlight the speed and efficiency of antigen recognition in vivo and
      add to our understanding of T cell-mediated autoimmunity.

PMID- 17213319
TI  - Alleviation of 1,N6-ethanoadenine genotoxicity by the Escherichia coli adaptive
      response protein AlkB.
AB  - 1,N(6)-ethanoadenine (EA) forms through the reaction of adenine in DNA with the
      antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea, a chemotherapeutic used to
      combat various brain, head, and neck tumors. Previous studies of the toxic and
      mutagenic properties of the DNA adduct EA have been limited to in vitro
      experiments using mammalian polymerases and have revealed the lesion to be both
      miscoding and genotoxic. This work explores lesion bypass and mutagenicity of EA
      replicated in vivo and demonstrates that EA is neither toxic nor mutagenic in
      wild-type Escherichia coli. Although the base excision repair glycosylase enzymes
      of both humans and E. coli possess a weak ability to act on the lesion in vitro,
      an in vivo repair pathway has not yet been demonstrated. Here we show that an
      enzyme mechanistically unrelated to DNA glycosylases, the adaptive response
      protein AlkB, is capable of acting on EA via its canonical mechanism of oxidative
      dealkylation. The reaction alleviates the unrepaired adduct's potent toxicity
      through metabolism at the C8 position (attached to N1 of adenine), producing a
      nontoxic and weakly mutagenic N(6) adduct. AlkB is shown here to be a geno
      protective agent that reduces the toxicity of DNA damage by converting the
      primary adduct to a less toxic secondary product.

PMID- 17213320
TI  - Inducible expression of the proallergic cytokine thymic stromal lymphopoietin in
      airway epithelial cells is controlled by NFkappaB.
AB  - The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) is important
      for the initiation of allergic airway inflammation through a dendritic cell
      mediated T helper 2 response. To identify the factors that control TSLP
      expression, we examined the ability of inflammatory mediators to regulate TSLP
      production in human airway epithelial cells. We found that both IL-1beta and TNF
      alpha were capable of inducing rapid TSLP production in primary human bronchial
      airway epithelial cells. We further characterized the human TSLP gene promoter,
      using two human epithelial cell lines, 16HBEo(-) and A549, and showed that IL
      1beta- and TNF-alpha-mediated human TSLP promoter activation in these cells was
      mediated by an upstream NFkappaB site. Mutation of this NFkappaB site abolished
      activation, as did overexpression of a dominant-negative version of IkappaB
      kinase (IKK)beta (a kinase acting on IkappaB, the inhibitor of NFkappaB).
      Interestingly, human TSLP mRNA levels were also increased after exposure to Toll
      like receptor (TLR) 2, TLR8, and TLR9 ligands, further supporting an important
      role for NFkappaB in TSLP gene regulation. Similarly, analysis of the mouse TSLP
      gene promoter revealed the presence of a similarly situated NFkappaB site that
      was also critical for IL-1beta-inducible expression of mouse TSLP. Taken
      together, these results demonstrate that the inflammatory mediators IL-1beta and
      TNF-alpha regulate human TSLP gene expression in an NFkappaB-dependent manner.

PMID- 17213318
TI  - Global patterns of diversification in the history of modern amphibians.
AB  - The fossil record of modern amphibians (frogs, salamanders, and caecilians)
      provides no evidence for major extinction or radiation episodes throughout most
      of the Mesozoic and early Tertiary. However, long-term gradual diversification is
      difficult to reconcile with the sensitivity of present-day amphibian faunas to
      rapid ecological changes and the incidence of similar environmental perturbations
      in the past that have been associated with high turnover rates in other land
      vertebrates. To provide a comprehensive overview of the history of amphibian
      diversification, we constructed a phylogenetic timetree based on a multigene data
      set of 3.75 kb for 171 species. Our analyses reveal several episodes of
      accelerated amphibian diversification, which do not fit models of gradual lineage
      accumulation. Global turning points in the phylogenetic and ecological
      diversification occurred after the end-Permian mass extinction and in the late
      Cretaceous. Fluctuations in amphibian diversification show strong temporal
      correlation with turnover rates in amniotes and the rise of angiosperm-dominated
      forests. Approximately 86% of modern frog species and >81% of salamander species
      descended from only five ancestral lineages that produced major radiations in the
      late Cretaceous and early Tertiary. This proportionally late accumulation of
      extant lineage diversity contrasts with the long evolutionary history of
      amphibians but is in line with the Tertiary increase in fossil abundance toward
      the present.

PMID- 17213321
TI  - The SCL transcriptional network and BMP signaling pathway interact to regulate
      RUNX1 activity.
AB  - Hematopoietic stem cell (HSC) development is regulated by several signaling
      pathways and a number of key transcription factors, which include Scl/Tal1,
      Runx1, and members of the Smad family. However, it remains unclear how these
      various determinants interact. Using a genome-wide computational screen based on
      the well characterized Scl +19 HSC enhancer, we have identified a related Smad6
      enhancer that also targets expression to blood and endothelial cells in
      transgenic mice. Smad6, Bmp4, and Runx1 transcripts are concentrated along the
      ventral aspect of the E10.5 dorsal aorta in the aorta-gonad-mesonephros region
      from which HSCs originate. Moreover, Smad6, an inhibitor of Bmp4 signaling, binds
      and inhibits Runx1 activity, whereas Smad1, a positive mediator of Bmp4
      signaling, transactivates the Runx1 promoter. Taken together, our results
      integrate three key determinants of HSC development; the Scl transcriptional
      network, Runx1 activity, and the Bmp4/Smad signaling pathway.

PMID- 17213322
TI  - Negative feedback loop in T cell activation through IkappaB kinase-induced
      phosphorylation and degradation of Bcl10.
AB  - Activation of the transcription factor NF-kappaB after stimulation through
      antigen receptors is important for lymphocyte differentiation, activation,
      proliferation, and protection against apoptosis. Much progress has been made in
      understanding the molecular events leading to NF-kappaB activation, but how this
      activation is eventually down-regulated is less well understood. Recent studies
      have indicated that Bcl10 functions downstream of lymphocyte antigen receptors to
      promote the activation of the IkappaB kinase complex leading to the
      phosphorylation and degradation of the IkappaB inhibitors of NF-kappaB. Bcl10 has
      also been implicated in the pathogenesis of mucosa-associated lymphoid tissue
      lymphoma, possibly in association with its nuclear localization. Here, we provide
      evidence that the IkappaB kinase complex phosphorylates Bcl10 after T cell
      antigen receptor stimulation and causes its proteolysis via the beta-TrCP
      ubiquitin ligase/proteasome pathway. These findings document a negative
      regulatory activity of the IKK complex and suggest that Bcl10 degradation is part
      of the regulatory mechanisms that precisely control the response to antigens.
      Mutants of Bcl10 in the IKK phosphorylation site are resistant to degradation,
      accumulate in the nucleus, and lead to an increase in IL-2 production after T
      cell antigen receptor stimulation.

PMID- 17213323
TI  - Smelling home can prevent dispersal of reef fish larvae.
AB  - Many marine fish and invertebrates show a dual life history where settled adults
      produce dispersing larvae. The planktonic nature of the early larval stages
      suggests a passive dispersal model where ocean currents would quickly cause
      panmixis over large spatial scales and prevent isolation of populations, a
      prerequisite for speciation. However, high biodiversity and species abundance in
      coral reefs contradict this panmixis hypothesis. Although ocean currents are a
      major force in larval dispersal, recent studies show far greater retention than
      predicted by advection models. We investigated the role of animal behavior in
      retention and homing of coral reef fish larvae resulting in two important
      discoveries: (i) Settling larvae are capable of olfactory discrimination and
      prefer the odor of their home reef, thereby demonstrating to us that nearby reefs
      smell different. (ii) Whereas one species showed panmixis as predicted from our
      advection model, another species showed significant genetic population
      substructure suggestive of strong homing. Thus, the smell of reefs could allow
      larvae to choose currents that return them to reefs in general and natal reefs in
      particular. As a consequence, reef populations can develop genetic differences
      that might lead to reproductive isolation.

PMID- 17213324
TI  - Ancestral genome sizes specify the minimum rate of lateral gene transfer during
      prokaryote evolution.
AB  - The amount of lateral gene transfer (LGT) that has occurred in microbial
      evolution is heavily debated. Efforts to quantify LGT through gene-tree
      comparisons have delivered estimates that between 2% and 60% of all prokaryotic
      genes have been affected by LGT, the 30-fold discrepancy reflecting differences
      among gene samples studied and uncertainties inherent in phylogenetic
      reconstruction. Here we present a simple method that is independent of gene-tree
      comparisons to estimate the LGT rate among sequenced prokaryotic genomes. If
      little or no LGT has occurred during evolution, ancestral genome sizes would
      become unrealistically large, whereas too much LGT would render them far too
      small. We determine the amount of LGT that is necessary and sufficient to bring
      the distribution of inferred ancestral genome sizes into agreement with that
      observed among modern microbes. Rather than testing for phylogenetic congruence
      or lack thereof across genes, we assume that all gene trees are compatible;
      hence, our method delivers very conservative lower-bound estimates of the average
      LGT rate. The results indicate that among 57,670 gene families distributed across
      190 sequenced genomes, at least two-thirds and probably all, have been affected
      by LGT at some time in their evolutionary past. A component of common ancestry
      nonetheless remains detectable in gene distribution patterns. We estimate the
      minimum lower bound for the average LGT rate across all genes as 1.1 LGT events
      per gene family and gene family lifespan and this minimum rate increases sharply
      when genes present in only a few genomes are excluded from the analysis.

PMID- 17213325
TI  - Small-molecule agonists for the glucagon-like peptide 1 receptor.
AB  - The peptide hormone glucagon-like peptide (GLP)-1 has important actions resulting
      in glucose lowering along with weight loss in patients with type 2 diabetes. As a
      peptide hormone, GLP-1 has to be administered by injection. Only a few small
      molecule agonists to peptide hormone receptors have been described and none in
      the B family of the G protein coupled receptors to which the GLP-1 receptor
      belongs. We have discovered a series of small molecules known as ago-allosteric
      modulators selective for the human GLP-1 receptor. These compounds act as both
      allosteric activators of the receptor and independent agonists. Potency of GLP-1
      was not changed by the allosteric agonists, but affinity of GLP-1 for the
      receptor was increased. The most potent compound identified stimulates glucose
      dependent insulin release from normal mouse islets but, importantly, not from GLP
      1 receptor knockout mice. Also, the compound stimulates insulin release from
      perfused rat pancreas in a manner additive with GLP-1 itself. These compounds may
      lead to the identification or design of orally active GLP-1 agonists.

PMID- 17213326
TI  - Characterization and application of single fluorescent nanodiamonds as cellular
      biomarkers.
AB  - Type Ib diamonds emit bright fluorescence at 550-800 nm from nitrogen-vacancy
      point defects, (N-V)(0) and (N-V)(-), produced by high-energy ion beam
      irradiation and subsequent thermal annealing. The emission, together with
      noncytotoxicity and easiness of surface functionalization, makes nano-sized
      diamonds a promising fluorescent probe for single-particle tracking in
      heterogeneous environments. We present the result of our characterization and
      application of single fluorescent nanodiamonds as cellular biomarkers. We found
      that, under the same excitation conditions, the fluorescence of a single 35-nm
      diamond is significantly brighter than that of a single dye molecule such as
      Alexa Fluor 546. The latter photobleached in the range of 10 s at a laser power
      density of 10(4) W/cm(2), whereas the nanodiamond particle showed no sign of
      photobleaching even after 5 min of continuous excitation. Furthermore, no
      fluorescence blinking was detected within a time resolution of 1 ms. The
      photophysical properties of the particles do not deteriorate even after surface
      functionalization with carboxyl groups, which form covalent bonding with polyL
      lysines that interact with DNA molecules through electrostatic forces. The
      feasibility of using surface-functionalized fluorescent nanodiamonds as single
      particle biomarkers is demonstrated with both fixed and live HeLa cells.

PMID- 17213327
TI  - Temperature control of larval dispersal and the implications for marine ecology,
      evolution, and conservation.
AB  - Temperature controls the rate of fundamental biochemical processes and thereby
      regulates organismal attributes including development rate and survival. The
      increase in metabolic rate with temperature explains substantial among-species
      variation in life-history traits, population dynamics, and ecosystem processes.
      Temperature can also cause variability in metabolic rate within species. Here, we
      compare the effect of temperature on a key component of marine life cycles among
      a geographically and taxonomically diverse group of marine fish and
      invertebrates. Although innumerable lab studies document the negative effect of
      temperature on larval development time, little is known about the generality
      versus taxon-dependence of this relationship. We present a unified, parameterized
      model for the temperature dependence of larval development in marine animals.
      Because the duration of the larval period is known to influence larval dispersal
      distance and survival, changes in ocean temperature could have a direct and
      predictable influence on population connectivity, community structure, and
      regional-to-global scale patterns of biodiversity.

PMID- 17213328
TI  - Axon guidance genes identified in a large-scale RNAi screen using the RNAi
      hypersensitive Caenorhabditis elegans strain nre-1(hd20) lin-15b(hd126).
AB  - The navigation of axons toward their targets is a highly dynamic and precisely
      regulated process during nervous system development. The molecular basis of this
      navigation process is only partly understood. In Caenorhabditis elegans, we
      isolated the RNAi-hypersensitive strain nre-1(hd20) lin-15b(hd126), which allows
      us to phenocopy axon guidance defects of known genes by feeding RNAi. We used
      this mutant strain to systematically screen 4,577 genes on chromosomes I and III
      for axon guidance phenotypes. We identified 93 genes whose down-regulation led to
      penetrant ventral cord fasciculation defects or motoneuron commissure outgrowth
      defects. These genes encode various classes of proteins, ranging from secreted or
      putative cell surface proteins to transcription factors controlling gene
      expression. A majority of the genes is evolutionary conserved and previously
      uncharacterized. In addition, we found axon guidance functions for known genes
      like pry-1, a component of the Wnt-signaling pathway, and ced-1, a receptor
      required for the engulfment of neurons undergoing apoptosis during development.
      Our screen provides insights into molecular pathways operating during the
      generation of neuronal circuits and provides a basis for a more detailed analysis
      of gene networks regulating axon navigation.

PMID- 17213329
TI  - The impact of structural biology on neurobiology.

PMID- 17213330
TI  - Membrane-embedded protease poses for photoshoot.

PMID- 17213331
TI  - Misassembled mutant DeltaF508 CFTR in the distal secretory pathway alters
      cellular lipid trafficking.
AB  - Most patients with cystic fibrosis (CF) have a single codon deletion (DeltaF508)
      in the gene encoding the cystic fibrosis transmembrane conductance regulator
      (CFTR) that impairs assembly of the multidomain glycoprotein. The mutant protein
      escapes endoplasmic reticulum (ER) quality control at low temperature, but is
      rapidly cleared from the distal secretory pathway and degraded in lysosomes. CF
      cells accumulate free cholesterol similar to Niemann-Pick disease type C cells.
      We show that this lipid alteration is caused by the presence of misassembled
      mutant CFTR proteins, including DeltaF508, in the distal secretory pathway rather
      than the absence of functional CFTR. By contrast, cholesterol distribution is not
      changed by either D572N CFTR, which does not mature even at low temperature, or
      G551D, which is processed normally but is inactive. On expression of the
      DeltaF508 mutant, cholesterol and glycosphingolipids accumulate in punctate
      endosomal structures and cholesterol esters are reduced, indicating a block in
      the translocation of cholesterol to the ER for esterification. This is overcome
      by Rab9 overexpression, resulting in clearance of accumulating intracellular
      cholesterol. Similar but less pronounced alterations in intracellular cholesterol
      distribution are observed on expression of a temperature-rescued mutant variant
      of the related ATP-binding cassette (ABC) protein multidrug resistance-associated
      protein 1 (MRP1). Thus, on escape from ER quality control, misassembled mutants
      of CFTR and MRP1 impair lipid homeostasis in endocytic compartments.

PMID- 17213332
TI  - Phosphorylation of Spc110p by Cdc28p-Clb5p kinase contributes to correct spindle
      morphogenesis in S. cerevisiae.
AB  - Spindle morphogenesis is regulated by cyclin-dependent kinases and monitored by
      checkpoint pathways to accurately coordinate chromosomal segregation with other
      events in the cell cycle. We have previously dissected the contribution of
      individual B-type cyclins to spindle morphogenesis in Saccharomyces cerevisiae.
      We showed that the S-phase cyclin Clb5p is required for coupling spindle assembly
      and orientation. Loss of Clb5p-dependent kinase abolishes intrinsic asymmetry
      between the spindle poles resulting in lethal translocation of the spindle into
      the bud with high penetrance in diploid cells. This phenotype was exploited in a
      screen for high dosage suppressors that yielded spc110(Delta)(13), encoding a
      truncation of the spindle pole body component Spc110p (the intranuclear receptor
      for the gamma-tubulin complex). We found that Clb5p-GFP was localised to the
      spindle poles and intranuclear microtubules and that Clb5p-dependent kinase
      promoted cell cycle dependent phosphorylation of Spc110p contributing to spindle
      integrity. Two cyclin-dependent kinase consensus sites were required for this
      phosphorylation and were critical for the activity of spc110(Delta)(13) as a
      suppressor. Together, our results point to the function of cyclin-dependent
      kinase phosphorylation of Spc110p and provide, in addition, support to a model
      for Clb5p control of spindle polarity at the level of astral microtubule
      organisation.

PMID- 17213333
TI  - After fertilization of sea urchin eggs, eIF4G is post-translationally modified
      and associated with the cap-binding protein eIF4E.
AB  - Release of eukaryotic initiation factor 4E (eIF4E) from its translational
      repressor eIF4E-binding protein (4E-BP) is a crucial event for the first mitotic
      division following fertilization of sea urchin eggs. Finding partners of eIF4E
      following fertilization is crucial to understand how eIF4E functions during this
      physiological process. The isolation and characterization of cDNA encoding
      Sphaerechinus granularis eIF4G (SgIF4G) are reported. mRNA of SgIF4G is present
      as a single 8.5-kb transcript in unfertilized eggs, suggesting that only one
      ortholog exists in echinoderms. The longest open reading frame predicts a
      sequence of 5235 nucleotides encoding a deduced polypeptide of 1745 amino acids
      with a predicted molecular mass of 192 kDa. Among highly conserved domains,
      SgIF4G protein possesses motifs that correspond to the poly(A) binding protein
      and eIF4E protein-binding sites. A specific polyclonal antibody was produced and
      used to characterize the SgIF4G protein in unfertilized and fertilized eggs by
      SDS-PAGE and western blotting. Multiple differentially migrating bands
      representing isoforms of sea urchin eIF4G are present in unfertilized eggs.
      Fertilization triggers modifications of the SgIF4G isoforms and rapid formation
      of the SgIF4G-eIF4E complex. Whereas rapamycin inhibits the formation of the
      SgIF4G-eIF4E complex, modification of these SgIF4G isoforms occurs independently
      from the rapamycin-sensitive pathway. Microinjection of a peptide corresponding
      to the eIF4E-binding site derived from the sequence of SgIF4G into unfertilized
      eggs affects the first mitotic division of sea urchin embryos. Association of
      SgIF4G with eIF4E is a crucial event for the onset of the first mitotic division
      following fertilization, suggesting that cap-dependent translation is highly
      regulated during this process. This hypothesis is strengthened by the evidence
      that microinjection of the cap analog m(7)GDP into unfertilized eggs inhibits the
      first mitotic division.

PMID- 17213334
TI  - Role of EGF-induced tyrosine phosphorylation of reggie-1/flotillin-2 in cell
      spreading and signaling to the actin cytoskeleton.
AB  - Cholesterol and sphingolipid-rich membrane microdomains or rafts have been shown
      to be involved in signaling through many growth factor receptors but the
      molecular details of these processes are not well understood. The
      reggie/flotillin proteins are ubiquitously expressed proteins with a poorly
      characterized function. They are constitutively associated with membrane rafts by
      means of acylation and oligomerization. Previous studies have implicated reggies
      in signaling, regulation of actin cytoskeleton and in membrane transport
      processes. In this study, we analyzed the putative role of reggie-1/flotillin-2
      in signaling through the epidermal growth factor receptor. We show that reggie-1
      becomes phosphorylated by Src kinase at several tyrosines upon stimulation of
      cells with epidermal growth factor. In addition, Src and reggie-1 are present as
      a molecular complex. Epidermal growth factor stimulation of cells results in a
      Tyr163-dependent translocation of reggie-1 from the plasma membrane into
      endosomes. We also show that reggie-1 is capable of enhancing the spreading of
      cells, again in a tyrosine-dependent manner, and knockdown of reggie-1 interferes
      with spreading. Thus, we reveal a new function for reggie-1 in the regulation of
      cell adhesion and actin dynamics and in growth factor signaling.

PMID- 17213335
TI  - Switch from BAX-dependent to BAX-independent germ cell loss during the
      development of fetal mouse ovaries.
AB  - Female reproductive life is limited by the oocyte/follicle pool, which has been
      determined by the number of germ cells to enter meiosis and subsequent loss of
      oocytes. It has been suggested that apoptosis accounts for the elimination of
      germ cells throughout oogenesis. However, female germ cells are lost continuously
      while they undergo distinct cell cycles in fetal and neonatal life. No convincing
      evidence has yet been provided to show apoptotic death of oocytes during meiotic
      prophase in vivo. In this study, we examined the change in the germ cell
      population in mice deficient of BAX, a key proapoptotic molecule. The number of
      germ cells, identified by GCNA1 immunolabeling, approximately doubled in ovaries
      of Bax(-/-) mice compared with ovaries of heterozygous Bax(+/-) mice and wild
      type Bax(+/+) mice by 14.5 days post coitum (d.p.c.) and remained higher up to
      24.5 d.p.c. However, there was a rapid loss of germ cells in Bax(-/-) ovaries,
      paralleling that in Bax(+/-) and Bax(+/+) ovaries from 14.5-24.5 d.p.c., a period
      in which most germ cells entered and progressed in meiotic prophase. These
      results suggest that, while progressing through meiotic prophase, oocytes are
      eliminated by a BAX-independent mechanism.

PMID- 17213336
TI  - Inhibition of de novo ceramide synthesis upregulates phospholipase D and enhances
      myogenic differentiation.
AB  - In L6 skeletal myoblasts induced to differentiate by Arg8-vasopressin treatment,
      a short-lived lowering of ceramide levels was observed, followed by a long
      lasting elevation that was prevented by inhibitors of the de novo synthesis
      pathway, fumonisin B1 and myriocin. Both inhibitors increased the expression of
      myogenic differentiation markers and cell fusion rate, whereas short-chain
      ceramides inhibited these responses. Similar drug effects were observed on
      primary mouse satellite cell differentiation. Furthermore, bacterial
      sphingomyelinase overexpression suppressed myogenin nuclear accumulation in L6
      cells. These data suggested that endogenous ceramide mediates a negative feedback
      mechanism limiting myogenic differentiation, and that inhibitors of ceramide
      synthesis promoted myogenesis by removing this control. Phospholipase D (PLD), a
      recognized target of ceramide, is required for myogenesis, as shown by the
      negative effects of PLD1 isoform depletion obtained by siRNA treatment. Fumonisin
      induced an increase in PLD activity of L6 cells, whereas C6-ceramide decreased
      it. The expression of PLD1 mRNA transcripts was selectively decreased by C6
      ceramide, and increased by ceramide synthesis inhibitors. An early step of
      myogenic response is the PLD1-dependent formation of actin stress fiber-like
      structures. C6-ceramide addition or overexpression of sphingomyelinase impaired
      actin fiber formation. Ceramide might thus regulate myogenesis through
      downregulation of PLD1 expression and activity.

PMID- 17213337
TI  - Ischaemia modified albumin in radiofrequency catheter ablation.
AB  - Aim Ischaemia modified albumin (IMA) is considered a marker of myocardial
      ischaemia, in contrast to the biomarkers of myocardial injury [creatine kinase
      (CK), the MB isoenzyme of CK, and cardiac troponin I (Tn-I)] that are released
      when cardiac necrosis occurs. Ischaemia modified albumin has been reported to
      increase following percutaneous coronary intervention and in acute coronary
      syndromes. We sought to determine whether IMA increases following radiofrequency
      (RF) ablation. METHODS AND RESULTS: We studied 40 consecutive patients who
      underwent RF catheter ablation; 20 were men and 20 women and their age was 47 +/-
      16 (16-77) years. All patients underwent electrophysiological study and
      subsequent RF ablation. Peripheral venous samples were collected before the
      procedure (baseline), immediately after the procedure, 2 h post-procedure and the
      following day (20 h post-procedure) and assayed for CK, the MB isoenzyme of CK,
      cardiac Tn-I and IMA. Ischaemia-modified albumin plasma levels did not differ
      significantly at all four time points, baseline, and following ablation (P =
      0.5974), whereas CK, CK-MB, and Tn-I increased significantly at all time points
      compared with baseline (P < 0.0001). Post-ablation, all but three 3 CK
      measurements were in the normal range; 14 patients had CK-MB plasma levels above
      the upper limit of normal; all but one patient had Tn-I elevated. CONCLUSION: The
      IMA plasma levels do not change significantly following RF ablation, unlike
      biomarkers of myocardial injury, implying that myocardial necrosis occurs without
      preceding ischaemia.

PMID- 17213338
TI  - KAL1 mutations are not a common cause of idiopathic hypogonadotrophic
      hypogonadism in humans.
AB  - Hypogonadotrophic hypogonadism results in the absence of puberty and if left
      untreated leads to infertility. Mutations in KAL1 are known to account for some
      of the cases of Kallmann syndrome. The aim of this study was to determine the
      prevalence of KAL1 mutations in a large number of patients with idiopathic
      hypogonadotrophic hypogonadism (IHH). One hundred and thirty eight patients (109
      males and 29 females) with IHH were studied for mutations in KAL1. DNA from these
      patients was subjected to denaturing gradient gel electrophoresis or single
      strand conformation polymorphism to identify mutations. Sequencing was performed
      to confirm mutations detected. Four mutations were found in 109 males (3.7%). All
      four mutations were in anosmic/hyposmic men making the prevalence 4/63 (6.3%) in
      this group of patients. No mutations were found in the 29 female patients. KAL1
      mutations are an uncommon cause of Kallmann syndrome.

PMID- 17213341
TI  - Religious belief, perceptions of human suffering, and support for reproductive
      genetic technology.
AB  - Reproductive genetic technologies are becoming more controversial as they become
      more ubiquitous. The opponents of these technologies are largely religious
      groups, a fact that leads to the question of why religious groups would be more
      opposed to these technologies than others. Since all of these technologies are
      justified by their ability to relieve suffering of some kind, it is hypothesized
      that the actively religious have a notion of suffering different from that of
      advocates for these technologies, and this different notion of suffering leads to
      opposition to the technologies. In this article I report on a qualitative
      interview study of the religiously active in the United States. I find that the
      religiously active do have views of suffering that are distinct from the medical
      consensus, and these views are related to people's conclusions about the
      advisability of reproductive genetic technologies.

PMID- 17213339
TI  - The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164
      increases steatosis in an in vitro cellular model.
AB  - BACKGROUND AND AIMS: The prevalence and severity of liver steatosis are higher in
      patients infected with genotype 3 hepatitis C virus (HCV) than in patients
      infected with other genotypes. HCV core protein is known to affect lipid
      metabolism, inducing lipid droplet accumulation both in vitro and in vivo. An in
      vitro cellular model was used to investigate whether an HCV core protein with
      residues specific to genotype 3 increased this phenomenon. METHODS: Sequence
      comparisons for HCV core protein domain II, which is known to interact with lipid
      droplets, identified the phenylalanine (F) residue at position 164 as the only
      residue specific to genotype 3. The area covered by lipid droplets in sections of
      cells producing a wild-type genotype 1a HCV core protein was compared with that
      in cells producing a Y164F mutant protein. RESULTS: Cumulative lipid droplet area
      was significantly greater in sections of cells producing the Y164F mutant HCV
      core protein than in cells producing the wild-type protein (p<0.001). The
      frequency of cell sections containing more than 3 mum(2) of lipid droplets, in
      particular, was higher for the mutant than for the wild-type protein. CONCLUSION:
      The data provide a molecular explanation for HCV genotype 3-specific lipid
      accumulation. This difference between genotypes may be due to phenylalanine
      having a higher affinity for lipids than tyrosine (Y). These observations provide
      useful information for further studies of the mechanisms involved in HCV-induced
      steatosis.

PMID- 17213340
TI  - Prognosis and risk factors of metastasis in colorectal carcinoids: results of a
      nationwide registry over 15 years.
AB  - BACKGROUND: Colorectal carcinoids are often described as low-grade malignant.
      However, no study has compared the survival between patients with colorectal
      carcinoids and those with carcinomas, in a large series. In addition, no global
      consensus has been established on the crucial determinants of metastasis in
      colorectal carcinoids. AIM: To determine the predictive factors for metastasis in
      colorectal carcinoids and clarify their prognosis compared with adenocarcinomas.
      METHODS: Data of all patients diagnosed as having colorectal carcinoids were
      extracted from a large nationwide database of colorectal tumours, the Multi
      Institutional Registry of Large-Bowel Cancer in Japan, for the period from 1984
      to 1998. Risk factors for lymph node (LN) metastases and distant metastases were
      analysed among those who were undergoing surgery, by univariate and multivariate
      analysis. Cancer-specific survival was also compared between patients with
      colorectal carcinoids and those with adenocarcinomas registered in the same
      period. RESULTS: Among the 90 057 cases of colorectal tumours that were
      diagnosed, a total of 345 cases of carcinoids were identified, including 247
      colorectal carcinoids of those undergoing surgery. Risk factors for LN metastasis
      were tumour size >/=11 mm and lymphatic invasion, whereas those for distant
      metastasis were tumour size >/=21 mm and venous invasion. Colorectal carcinoids
      without these risk factors exhibited no LN metastasis or distant metastasis.
      Cancer-specific survival of patients with colorectal carcinoids without
      metastasis was better than that of those with adenocarcinomas. However, the
      survival was similar between carcinoids and adenocarcinomas if the tumours had LN
      metastasis or distant metastasis. CONCLUSIONS: The presence of metastasis in
      colorectal carcinoids could lead to survival that is as poor as in
      adenocarcinomas. Tumours </=10 mm and without lymphatic invasion could be
      curatively treated by local resection, but others would need radical LN
      dissection.

PMID- 17213342
TI  - Patient inducement, provider priorities, and resource allocation in public mental
      health systems.
AB  - Public mental health systems are increasingly facing demands from the criminal
      justice system and social services agencies to provide services and support in
      cases in which mental illness contributes to crime, homelessness, or poverty. In
      this article we analyze how policies from outside public mental health systems
      affect resource allocation within these systems, using examples from criminal
      justice. These policies use two types of mechanisms: inducing patients to consume
      treatment (by offering rewards or imposing penalties) and inducing clinicians to
      provide treatment (by creating priorities). We propose a classification of these
      social policies based on whether they affect demand through rewards or penalties
      or supply through priorities. We then relate the classification to data on
      patients treated in public systems to evaluate the current prevalence and
      potential for growth in these outside demands. These inducements impose a set of
      nonobvious costs on other patients who are not targeted by the policies.
      Furthermore, they create incentives for both patients and providers to modify
      their behavior in order to take advantage of rewards, avoid penalties, or better
      compete for resources with prioritized patients. We consider some policy
      implications for avoiding unintended consequences of these policies.

PMID- 17213343
TI  - Differential effectiveness in patient protection laws: what are the causes? An
      example from the drive-through delivery laws.
AB  - In the mid-1990s, many states as well as the federal government began to regulate
      early postpartum hospital discharge. Length-of-stay patterns changed markedly in
      response, but effects were much greater in some states than others. In
      particular, laws directly empowering patients appeared more effective than laws
      requiring providers to follow practice guidelines. In addition, the effectiveness
      of regulation could potentially be influenced by state environment, such as
      managed care penetration as well as exposure to media attention and public
      pressure on the issue, though these factors alone were insufficient to cause
      general behavior change. Furthermore, the 1996 federal law had little effect
      beyond state laws, suggesting that it did not provide substantial benefits to
      women in self-insured plans exempted from state law regulation by the Employee
      Retirement Income Security Act. Findings from this study could provide lessons
      for similar patient protection initiatives.

PMID- 17213344
TI  - Should providers be allowed to extra bill for uncovered services? Debate,
      resolution, and sequel in Japan.
AB  - Japan has managed to provide universal coverage at relatively low cost by
      containing prices and restricting the conditions for which services can be billed
      in the compulsory social health insurance (SHI) program. However, decline in
      Japan's economic growth ushered in new actors backed by the prime minister who
      proposed that the providers should be allowed to extra bill for services not
      covered by the SHI. In 2004 they took the strategy of drawing the attention of
      the public to areas where the rigidity of the current prohibition appeared to be
      unfair and ridiculous. They were opposed by the Ministry of Health, Labor, and
      Welfare and the Japan Medical Association, who strongly objected on the grounds
      of safety and equity. The compromise reached by the two ministers in charge led
      to a clarification of the services that are to be covered and of the process for
      extending coverage to new procedures and drugs. The prohibition on extra billing
      has remained essentially unchanged, but the momentum for deregulation has been
      lost. In 2005 an alternate proposal was made to contain SHI expenditures by
      introducing a global cap on health expenditures and increasing out-of-pocket
      payment. Although this proposal was not fully adopted, the gradual decline in SHI
      benefit levels could lead to a renewed move to allow extra billing.

PMID- 17213345
TI  - Biologic therapies: what and when?
AB  - Over the past two decades, major advances have been made in the understanding of
      the immune system and disease pathogenesis. This has coincided with the
      development of biologic therapies--monoclonal antibodies and fusion proteins. The
      decision of when to use such treatment in the clinic is not always
      straightforward. In addition to immune biology, the focus of this review will be
      on the application of these treatments to immune-mediated diseases and the
      molecular targets involved in pathogenesis, specifically those that have US Food
      and Drug Administration/European Medicines Agency approval. Brief comments will
      be made on biologics that have approval for non-immune disorders.

PMID- 17213346
TI  - Distinguishing diabetic nephropathy from other causes of glomerulosclerosis: an
      update.
AB  - Diabetic nephropathy is a common cause of end-stage renal disease worldwide. It
      is characterised by diffuse or nodular glomerulosclerosis, afferent and efferent
      hyaline arteriolosclerosis, and tubulointerstitial fibrosis and atrophy. Diffuse
      and nodular diabetic glomerulosclerosis share similar histological features with
      other clinical conditions. Immunofluorescence and electron microscopy studies,
      and clinicopathological correlation are essential to differentiate diabetic
      nephropathy from other conditions that result in diffuse and nodular
      glomerulosclerosis.

PMID- 17213347
TI  - Diagnosis of adenocarcinoma in prostate needle biopsy tissue.
AB  - Prostate cancer is a major public health problem throughout the developed world.
      For patients with clinically localised prostate cancer, the diagnosis is
      typically established by histopathological examination of prostate needle biopsy
      samples. Major and minor criteria are used to establish the diagnosis, based on
      the microscopic appearance of slides stained using haematoxylin and eosin. Major
      criteria include an infiltrative glandular growth pattern, an absence of basal
      cells and nuclear atypia in the form of nucleomegaly and nucleolomegaly. In
      difficult cases, basal cell absence may be confirmed by immunohistochemical
      stains for high-molecular-weight cytokeratins (marked with antibody 34betaE12) or
      p63, which are basal cell markers. Minor criteria include intraluminal wispy blue
      mucin, pink amorphous secretions, mitotic figures, intraluminal crystalloids,
      adjacent high-grade prostatic intraepithelial neoplasia, amphophilic cytoplasm
      and nuclear hyperchromasia. Another useful diagnostic marker detectable by
      immunohistochemistry is alpha-methylacyl coenzyme A racemase (AMACR), an enzyme
      selectively expressed in neoplastic glandular epithelium. Cocktails of antibodies
      directed against basal cell markers and AMACR are particularly useful in
      evaluating small foci of atypical glands, and in substantiating a diagnosis of a
      minimal adenocarcinoma. Reporting of adenocarcinoma in needle biopsy specimens
      should always include the Gleason grade and measures of tumour extent in the
      needle core tissue. Measures of tumour extent are (1) number of cores positive
      for cancer in the number of cores examined, (2) percentage of needle core tissue
      affected by carcinoma and (3) linear millimetres of carcinoma present.

PMID- 17213348
TI  - Immunohistological analysis of immune cells in blistering skin lesions.
AB  - BACKGROUND: Bullous skin lesions are characterised by the presence of
      intraepidermal or subepidermal bullae. Although inflammatory cell infiltrate is a
      constant feature in these lesions, their immunophenotypic characterisation is
      still incomplete. AIM: To determine whether the development of bullous skin
      diseases is associated with changes in the inflammatory cell infiltrate.
      MATERIALS AND METHODS: 34 cases representing lesions with both intraepidermal and
      subepidermal bullae were examined using immunoperoxidase staining methods and
      antibodies targeting antigens for histiocytes (CD68), B cells (CD20+), T cells
      (CD3+), T cells with cytotoxic potential (T cell intracellular associated
      antigen, TIA1+) and activity (granzyme B, GRB+). The adjacent normal skin
      (lesions) and an additional five cases of normal skin were also examined
      (controls). RESULTS: The transition from normal skin to lesional skin (lesions
      with intraepidermal and subepidermal bullae) was associated with a significant
      increase (p< or =0.05) in the density of total inflammatory cell infiltrate,
      CD68+ cells, CD3+ T lymphocytes, CD20+ B lymphocytes, TIA1+ -resting cytotoxic T
      cells and GRB+ T cells with cytotoxic activity. CONCLUSIONS: The increase in
      inflammatory cell infiltrate during the transition from normal to lesional skin
      may reflect the presence of an increased antigenicity of the lesional cells or a
      response to some basement membrane components. CD68+ and CD3+ cells, especially
      the resting cytotoxic ones, achieved numerical dominance in these lesions. Cell
      mediated immunity seems to have critical role in the development of these
      lesions.

PMID- 17213349
TI  - Plasmablastic lymphoma presenting as a paravertebral mass in a patient with
      Crohn's disease after immunosuppressive therapy.
AB  - The case of a 32-year-old man with a paravertebral mass and skin nodules,
      occurring against a background of immunosuppressive therapy for Crohn's disease,
      is presented. The tumours showed morphological and immunophenotypical features of
      plasmablastic lymphoma. To our knowledge, this is the first reported case of
      plasmablastic lymphoma presenting in this location, and also after
      immunosuppression with infliximab treatment for Crohn's disease.

PMID- 17213350
TI  - Infiltrating giant cellular blue naevus.
AB  - INTRODUCTION: Cellular blue naevi (CBN) measure 1-2 cm in diameter and affect the
      dermis, occasionally extending into the subcutaneous fat. The case of a 14-year
      old boy with a giant CBN (GCBN) involving the right half of the face, the jugal
      mucosa and the lower eyelid with a tumour that had infiltrated the bone and the
      maxillary and ethmoidal sinuses is reported. METHODS: Biopsies were taken from
      the skin, jugal mucosa and maxillary sinus. The following markers were used in
      the immunohistochemical evaluation: CD34, CD56, HMB-45, anti-S100, A-103, Melan A
      and MIB-1. RESULTS: The biopsy specimens showed a biphasic pattern affecting the
      lower dermis, subcutaneous fat, skeletal muscle, bone, jugal mucosa and maxillary
      sinus, but there was no histological evidence of malignancy. The tumour cells
      were CD34-, CD56-, HMB45+, anti-S100+ and A-103+. Melan A was focally expressed.
      No positive MIB-1 cells were identified. DISCUSSION: The present case shows that
      GCBN may infiltrate deeply, with no evidence of malignancy.

PMID- 17213351
TI  - Adenocarcinoma arising in a gastrocystoplasty.
AB  - Gastrocystoplasty is a form of surgical bladder augmentation or neobladder used
      to restore bladder capacity and compliance in children and in patients with
      neurogenic bladder. Other forms of bladder augmentation include ileocystoplasty
      and colocystoplasty. Reported complications of gastrocystoplasty include post
      operative bleeding, haematuria, stricture, metabolic alkalosis and rupture of the
      gastric segment. There are reports of adenocarcinomas arising in the setting of
      ileocystoplasty and colocystoplasty. However, the first case of adenocarcinoma
      arising in the setting of a gastrocystoplasty is reported.

PMID- 17213352
TI  - Embryonal rhabdomyosarcoma of the cervix with focal pleomorphic areas.
AB  - An embryonal rhabdomyosarcoma (sarcoma botryoides) of the cervix occurring in a
      30-year-old woman is described. In addition to typical areas of the embryonal
      rhabdomyosarcoma, including cartilaginous elements, the neoplasm was
      characterised by the presence of foci composed of highly pleomorphic cells. The
      significance of this finding is uncertain. These foci may represent areas of
      dedifferentiation in an embryonal rhabdomyosarcoma.

PMID- 17213353
TI  - Disseminated gonococcal infection presenting as vasculitis: a case report.
AB  - A 50-year-old man with alcoholic liver disease presented with fever,
      tenosynovitis, polyarthritis and a vasculitic rash on the hands and feet for 4
      days. He had neutrophilia and raised inflammatory markers. He had no history of
      sore throat, urethral discharge or travel abroad. His initial blood cultures were
      negative, and he was treated for vasculitis with steroids. The rash and arthritis
      seemed to improve initially, but he had another episode of fever. Repeat blood
      cultures grew Neisseria gonorrhoeae,and he received intravenous ceftriaxone
      followed by oral ciprofloxacin. He had marked improvement in rash, tenosynovitis
      and arthritis, and the fever dropped. He also had chlamydial urethritis and
      received azithromycin. The presentation of disseminated gonococcal infection
      after a presumptive episode of asymptomatic urethral gonorrhoea is highlighted.

PMID- 17213354
TI  - Aortic stenosis in cardiovascular ochronosis.
AB  - Alkaptonuria (endogenous ochronosis) is a rare metabolic disorder caused by a
      deficiency of homogentisic acid oxidase, an enzyme responsible for the metabolic
      degradation of tyrosine. Patients with alkaptonuria commonly present with joint
      pain owing to degenerative arthritis. Other affected patients may present with
      pigmentation of the ear cartilage and sclera. This article reports a case of
      aortic stenosis associated with ochronosis in a 48-year-old man who presented
      with severe cardiac failure. He had no previous diagnosis of alkaptonuria, which
      was confirmed by mass spectrometry analysis of urine. The pathogenesis of
      cardiovascular ochronosis is unclear, but is probably related to the extensive
      extracellular deposits of ochronotic pigment in the cardiac tissue.

PMID- 17213355
TI  - Non-atherosclerotic coronary pathology causing sudden death.
AB  - Coronary atherosclerosis is responsible for >50% of all cases of sudden death and
      for 90% of sudden coronary death. Four cases encountered in routine autopsy
      evaluation at our institute in 2004 in which non-atherosclerotic coronary
      pathology was responsible for sudden cardiac death are reported. The cases of a
      31-year-old man with epicardial coronary arteritis, a 57-year-old man with
      intramyocardial vasculitis, a 45-year-old woman with spontaneous coronary
      dissection and a 50-year-old man with vascular fibrosis are described. Searching
      for non-atherosclerotic coronary disease is relevant for both the clinician and
      the pathologist to prevent coronary causes of sudden death going unrecognised.

PMID- 17213356
TI  - Mixed epithelial and stromal tumour of the kidney with luteinised ovarian stroma.
AB  - We report a case of a 9-cm mixed epithelial and stromal tumour of the kidney in
      an obese 70-year-old woman with diabetes. The ovarian-type stroma had a spindle
      cell component that was positive for progesterone receptors and had the hitherto
      unreported presence of abundant foci of luteinised stromal cells with
      characteristic immunohistochemical positivity to alpha-inhibin, calretinin,
      aromatase and gonadotropin-releasing hormone (GnRH) receptors. We conclude that
      the stromal component is identical to ovarian cortical stroma. We believe that
      ovarian-type stroma occurs in extragenital tumours as a result of an epithelial
      stromal interaction in an environment of hormonal hyperstimulation.

PMID- 17213357
TI  - Massive expansion of EBV+ monoclonal T cells with CD5 down regulation in EBV
      associated haemophagocytic lymphohistiocytosis.
AB  - Haemophagocytic lymphohistiocytosis (HLH) comprises primary and secondary forms;
      the secondary form is most commonly triggered by the Epstein-Barr virus (EBV; EBV
      HLH). Patients with EBV-HLH usually exhibit oligoclonal or monoclonal T cell
      proliferation, which may mimic T cell lymphoproliferative disorder (T-LPD). This
      article reports on EBV-HLH in a 17-month-old girl with an extreme surge of
      reactive T lymphocytosis (absolute count 167x10(9)/l) with CD5 down regulation.
      Bone marrow aspirate and trephine contained florid haemophagocytosis and massive
      infiltration of CD3+ Epstein-Barr virus-encoded RNA+ lymphocytes, as seen by
      double labelling. These lymphocytes were monoclonal for EBV and T cell receptor
      gamma chain gene rearrangement. The patient responded dramatically to intravenous
      immunoglobulin, interferon alpha2b, ganciclovir and prednisolone, suggesting
      restoration of her immune system and eradication of the clonal T cells through
      these immunoregulatory agents. Thus, careful clinicopathological correlation is
      warranted in the interpretation of immunophenotyping and clonality data in T cell
      proliferation in association with EBV-HLH to avoid erroneous diagnosis of T-LPD.

PMID- 17213358
TI  - Aberrant gene methylation implicated in the progression of monoclonal gammopathy
      of undetermined significance to multiple myeloma.
AB  - Malignant transformation is a multistep process that may involve dysregulation of
      oncogenes and tumour suppressor genes, and monoclonal gammopathy of undetermined
      significance (MGUS) is believed to be a precursor of multiple myeloma. To
      investigate whether aberrant promoter methylation might be involved in the
      evolution of MGUS to multiple myeloma, we examined the p16, protein tyrosine
      phosphatase, non-receptor type 6 (SHP1), death-associated protein (DAP) kinase, E
      cadherin and oestrogen receptor genes, most being tumour suppressor genes, by
      methylation-specific polymerase chain reaction. In 32 cases of multiple myeloma
      and 19 cases of MGUS, significantly more frequent methylation of p16 (p = 0.001),
      SHP1 (p< or =0.001) and E-cadherin (p< or =0.001) genes was found in multiple
      myeloma than in MGUS. Methylation of DAP kinase and oestrogen receptor genes was
      comparable in multiple myeloma and MGUS. In conclusion, methylation of p16, SHP1
      and E-cadherin genes might be involved in the progression of MGUS to multiple
      myeloma.

PMID- 17213359
TI  - Diagnostic relevance of anti-filamentous actin antibodies in autoimmune
      hepatitis.

PMID- 17213360
TI  - Anaplastic large cell lymphoma presenting with paraneoplastic pemphigus.

PMID- 17213361
TI  - Enteropathy type T cell lymphoma with an unusually late relapse: a case report.

PMID- 17213362
TI  - Vulval intraepithelial neoplasia with extra mammary Pagets disease: a rare
      association.

PMID- 17213363
TI  - Multiple myeloma uncovered by investigating a negative serum iron level.

PMID- 17213364
TI  - Gadolinium-based MR contrast agents and nephrogenic systemic fibrosis.

PMID- 17213366
TI  - Proteomics study of neuropathic and nonneuropathic dorsal root ganglia: altered
      protein regulation following segmental spinal nerve ligation injury.
AB  - Peripheral nerve injury is often followed by the development of severe
      neuropathic pain. Nerve degeneration accompanied by inflammatory mediators is
      thought to play a role in generation of neuropathic pain. Neuronal cell death
      follows axonal degeneration, devastating a vast number of molecules in injured
      neurons and the neighboring cells. Because we have little understanding of the
      cellular and molecular mechanisms underlying neuronal cell death triggered by
      nerve injury, we conducted a proteomics study of rat 4th and 5th lumbar (L4 and
      L5) dorsal root ganglion (DRG) after L5 spinal nerve ligation. DRG proteins were
      displayed on two-dimensional gels and analyzed through quantitative densitometry,
      statistical validation of the quantitative data, and peptide mass fingerprinting
      for protein identification. Among approximately 1,300 protein spots detected on
      each gel, we discovered 67 proteins that were tightly regulated by nerve
      ligation. We find that the injury to primary sensory neurons turned on multiple
      cellular mechanisms critical for the structural and functional integrity of
      neurons and for the defense against oxidative damage. Our data indicate that the
      regulation of metabolic enzymes was carefully orchestrated to meet the altered
      energy requirement of the DRG cells. Our data also demonstrate that ligation of
      the L5 spinal nerve led to the upregulation in the L4 DRG of the proteins that
      are highly expressed in embryonic sensory neurons. To understand the molecular
      mechanisms underlying neuropathic pain, we need to comprehend such dynamic aspect
      of protein modulations that follow nerve injury.

PMID- 17213367
TI  - Microarray and real-time PCR analysis of adrenal gland gene expression in the 7
      day-old rat: effects of hypoxia from birth.
AB  - We hypothesize that changes in adrenal gene expression mediate the increased
      plasma corticosterone and steroidogenesis in rat pups exposed to hypoxia from
      birth. In the current study, rat pups (with their dams) were exposed to hypoxia
      from birth and compared with pups from normoxic dams fed ad libitum or pair fed
      to match the decreased maternal food intake that occurs during hypoxia.
      Microarray analysis was performed, followed by verification with real-time PCR.
      Furthermore, the expression of selected genes involved in adrenal function was
      analyzed by real-time PCR, regardless of microarray results. Hypoxia increased
      plasma ACTH and corticosterone, while food restriction had no effect. Microarray
      revealed that many of the genes affected by hypoxia encode proteins that require
      molecular oxygen (monooxygenases, oxidoreductases, and electron transport),
      whereas only a few genes known to be involved in adrenal steroidogenesis were
      affected. Interestingly, the expression of genes involved in mitochondrial
      function and intermediary metabolism was increased by hypoxia. Real-time PCR
      detected a small but significant increase in the expression of Cyp21a1 mRNA in
      the hypoxic adrenal. When decreased maternal food intake was controlled for, the
      effects of hypoxia were more pronounced, in that real-time PCR detected
      significant increases in the expression of Star (244%), Cyp21a1 (208%), and Ldlr
      (233%). The present study revealed that increased plasma corticosterone in rat
      pups was due to hypoxia per se, and not as a result of decreased food intake by
      the hypoxic dam. Furthermore, hypoxia induced changes in gene expression that
      account for more productive and efficient steroidogenesis.

PMID- 17213369
TI  - 1alpha,25-dihydroxy-vitamin D3 stimulation of bronchial smooth muscle cells
      induces autocrine, contractility, and remodeling processes.
AB  - Genetic variants in the vitamin D receptor (VDR) gene were recently associated
      with asthma. The biological mechanisms explaining this association are unknown
      but are likely to involve many cell types given the pleiotropic effect of its
      ligand, 1alpha,25-dihydroxy-vitamin D3 [1alpha,25(OH)2D3]. Considering the
      prominent role of bronchial smooth muscle cells (BSMCs) in the pathogenesis of
      asthma, experiments were conducted to explore the gene regulatory effects of
      1alpha,25(OH)2D3 in these cells. Using RT-PCR and Western blot, we showed that
      VDR is present both at the mRNA transcript and protein levels in human BSMCs. The
      functionality of the receptor was then demonstrated by showing a >200-fold change
      in the expression of the 24-hydroxylase (CYP24A1) gene following 1alpha,25(OH)2D3
      stimulation. Microarray experiments were then performed to identify
      differentially regulated genes and pathways in BMSCs treated or not with
      1alpha,25(OH)2D3. A total of 729 probe sets on the U133 plus 2.0 Affymetrix
      GeneChip showed fold-change differences above the 1.5 threshold using the Robust
      Multichip Average intensities. This corresponds to 231 unique genes that were
      upregulated and 215 unique genes that were down-regulated following
      1alpha,25(OH)2D3 stimulation. A high similarity between microarray and real-time
      PCR results was observed for 13 random genes, with a concordance correlation
      coefficient of 0.91. Real-time PCR was also performed to confirm the regulation
      of asthma candidate genes. To identify the biological relevance of this
      regulation, biological pathways analyses were performed. The most significant
      network of upregulated genes included genes involved in morphogenesis, cell
      growth, and survival as well as genes encoding structural proteins, which are
      potentially involved in airway remodeling.

PMID- 17213368
TI  - Metabolic and genomic dissection of diabetes in the Cohen rat.
AB  - We investigated the metabolic and genetic basis of diabetes in the Cohen Diabetic
      rat, a model of diet-induced diabetes, as a means to identify the molecular
      mechanisms involved. By altering individual components in the diabetogenic diet,
      we established that the dietary susceptibility that leads to the development of
      diabetes in this model is directly related to the high casein and low copper
      content in chow. The development of diabetes is accompanied by depletion of the
      acini from the exocrine pancreas and replacement with fat cells, while the
      appearance of the islets of Langerhans remains intact. With reversion back from
      diabetogenic to regular diet, the diabetic phenotype disappears but the
      histological changes in the exocrine pancreas prevail. Using positional cloning,
      we detected a major quantitative trait locus (QTL) on rat chromosome 4 with a
      chromosomal span of 4.9 cM, and two additional loci on chromosomes 7 and X. A
      screen for genes within that QTL in the rat and in the syntenic regions in mouse
      and man revealed only 23 candidate genes. Notable among these genes is Ica1,
      which has been causally associated with diabetes and bovine casein. We conclude
      that the development of diabetes in our model is dependent upon high casein and
      low copper in diet, that it is accompanied by histomorphological changes in the
      exocrine but not endocrine pancreas, that it is reversible, and that it is
      associated with a major QTL on chromosome 4 in which we detected Ica1, a high
      priority candidate gene.

PMID- 17213372
TI  - The why, when, what, where, and how of graduate school.

PMID- 17213373
TI  - "Health for all": An ethical imperative or unattainable ideal?

PMID- 17213374
TI  - The clinical significance of subsyndromal depression in older primary care
      patients.
AB  - OBJECTIVE: Many seniors experience depressive symptoms not meeting standard
      diagnostic criteria. The authors sought to examine the clinical correlates of
      older primary care patients with "subsyndromal depression" (SSD), hypothesizing
      that SSD subjects have greater symptoms and functional impairment than
      nondepressed patients, but not as severe as those with major or minor depression,
      and to explore the characteristics of subjects captured by three different
      definitions of SSD used in prior published work. METHODS: The authors conducted a
      cross-sectional case comparison study that enrolled 662 primary care patients age
      >or=65 years. Outcomes were validated measures of psychopathology, medical
      illness burden, and functional status. RESULTS: All three SSD groups captured
      patients with greater symptoms and functional impairment than the nondepressed
      group. SSD subjects were as ill as those with minor or major depression on some
      measures (e.g., medical burden). Each SSD group definition captured some subjects
      unique to that group. CONCLUSIONS: Subsyndromal depression is common and
      associated with symptoms or impairments of clinical importance. Sole reliance on
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition definitions
      of major or minor depression omit a substantial proportion of seniors with
      clinically significant depressive symptoms. Longitudinal study is needed to help
      clinicians identify those at greatest risk for poor outcomes, while researchers
      testing mechanistic models should include patients with SSD to determine whether
      they share pathogenetic underpinnings with more severe mood disorders.

PMID- 17213375
TI  - Epidemiology of social phobia in later life.
AB  - OBJECTIVE: Although anxiety disorders, including social phobia (SP), are common
      among older adults, very little is known about the epidemiology of SP in later
      life. METHOD: Using data drawn from a large, nationally representative sample of
      older adults from Canada (N=12,792), the authors estimate lifetime and 12-month
      prevalence of social phobia and examine demographic predictors and patterns of
      comorbidity of current SP in this population. RESULTS: The results reveal that SP
      is a prevalent disorder in later life with lifetime and 12-month prevalence
      estimates of 4.94% and 1.32%, respectively. Current SP (12-month) declines with
      age and is more common in individuals with other psychiatric disorders.
      Interestingly, there is no correlation between current SP and gender, marital
      status, or socioeconomic status. CONCLUSIONS: SP remains a highly prevalent
      disorder even in late life with the pattern of feared/avoided situations being
      strikingly similar to that of younger populations.

PMID- 17213376
TI  - Intensive insulin therapy in critical care: a review of 12 protocols.
AB  - OBJECTIVE: To review performance characteristics of 12 insulin infusion
      protocols. RESEARCH DESIGN AND METHODS: We systematically identify and compare 12
      protocols and then apply the protocols to generate insulin recommendations in the
      management of a patient with hyperglycemia. The main focus involves a comparison
      of insulin doses and patterns of insulin administration. RESULTS: There is great
      variability in protocols. Areas of variation include differences in initiation
      and titration of insulin, use of bolus dosing, requirements for calculation in
      adjustment of the insulin infusion, and method of insulin protocol adjustments.
      Insulin recommendations for a sample patient are calculated to highlight
      differences between protocols, including the patterns and ranges of insulin dose
      recommended (range 27-115 units [mean +/- SD 66.7 +/- 27.9]), amount recommended
      for glucose readings >200 mg/dl, and adjustments nearing target glucose.
      CONCLUSIONS: The lack of consensus in the delivery of intravenous insulin
      infusions is reflected in the wide variability of practice noted in this survey.
      This mandates close attention to the choice of a protocol. One protocol may not
      suffice for all patients.

PMID- 17213377
TI  - Closing the gap: Orthopaedic research in clinical practice.

PMID- 17213378
TI  - The efficacy of subacromial corticosteroid injection in the treatment of rotator
      cuff disease: A systematic review.
AB  - To investigate whether subacromial corticosteroid injections are effective in the
      treatment of rotator cuff disease, an evidence-based systematic review was
      undertaken of nine randomized controlled trials that compared subacromial
      corticosteroid injection with placebo in patients with rotator cuff disease. Each
      study was systematically evaluated for biases, and outcome measures were
      scrutinized for statistical significance and clinical importance. One study
      demonstrated clinically important differences in pain relief. Two studies showed
      clinically important improvement in range of motion at final follow-up. This
      systematic review of the available literature indicates that there is little
      reproducible evidence to support the efficacy of subacromial corticosteroid
      injection in managing rotator cuff disease.

PMID- 17213380
TI  - Malunion of the distal radius.
AB  - Fractures of the distal radius are common injuries. Acceptable results typically
      can be obtained with appropriate surgical or nonsurgical management. However, a
      small percentage of these fractures can progress to symptomatic malunion, which
      traditionally has been treated with osteotomy of the distal radius. Proper
      understanding of anatomy, biomechanics, indications, and contraindications can
      help guide patient selection for surgery. In formulating a treatment plan, the
      surgeon also must consider such technical variables as the type of osteotomy, the
      use of bone graft or bone-graft substitute, and the means of fixation to
      stabilize the osteotomy. Simultaneous implementation of an ulnar-side procedure,
      an intra-articular osteotomy, and soft-tissue releases also may be necessary.
      Some cases may be more appropriate for wrist fusion or other salvage procedures.

PMID- 17213379
TI  - Innovations in the management of displaced proximal humerus fractures.
AB  - The management of displaced proximal humerus fractures has evolved toward humeral
      head preservation, with treatment decisions based on careful assessment of
      vascular status, bone quality, fracture pattern, degree of displacement, and
      patient age and activity level. The AO/ASIF fracture classification is helpful in
      guiding treatment and in stratifying the risk for associated disruption of the
      humeral head blood supply. Nonsurgical treatment consists of sling
      immobilization. For patients requiring surgery, options include closed reduction
      and percutaneous fixation; transosseous suture fixation; open reduction and
      internal fixation, with either conventional or locking plate fixation; bone
      graft; and hemiarthroplasty. Proximal humerus fractures must be evaluated on an
      individual basis, with treatment tailored according to patient and fracture
      characteristics.

PMID- 17213381
TI  - Radial longitudinal deficiency.
AB  - Radial longitudinal deficiency encompasses a spectrum of upper limb dysplasias
      and hypoplasias. The bony abnormalities of the thumb and radius are the most
      pronounced, but deficiencies of the accompanying muscles, nerves, vessels, and
      joints also greatly influence the ultimate upper extremity function. The striking
      clinical presentation of the involved upper limb is often more obvious than the
      potentially life-threatening associated systemic conditions. All children
      presenting with radial longitudinal deficiency, regardless of severity, require a
      renal ultrasound, echocardiogram, and complete blood count to evaluate the
      potential for associated systemic conditions; these include Fanconi's anemia, the
      Holt-Oram syndrome, and the VATER (vertebral anomalies, anal atresia,
      tracheoesophageal fistula, esophageal atresia, renal agenesis) syndrome or
      VACTERL (vertebral anomalies, anal atresia, cardiac abnormalities,
      tracheoesophageal fistula, renal agenesis, and limb defects) association. The
      overall health of the child, as well as the severity of the osseous and soft
      tissue deformities of the affected limb, guides the long-term treatment plans.

PMID- 17213382
TI  - Wear and osteolysis around total knee arthroplasty.
AB  - Osteolysis induced by wear debris of ultra-high-molecular-weight polyethylene has
      emerged as a significant problem after total knee arthroplasty. The generation of
      polyethylene wear and the development of osteolysis around total knee
      arthroplasty are caused by a combination of patient, implant, and surgical
      factors. Activity level over time may be the most important patient factor
      affecting the loads placed on a total knee replacement, but it is the most
      difficult to manage. Multiple factors related to the manufacturing of the
      polyethylene implant influence the extent of wear, and surgeons should be
      cautious in considering enhanced polyethylenes pending results of further
      investigations. The optimal design of the articular bearing surface remains
      controversial but needs to be considered with respect to the stresses imparted on
      component-bone and modular tibial backside interfaces. Surgical factors,
      including restoration of alignment and ligament balance, are important for long
      term durability of the implant. Methods of measuring the wear of total knee
      implants are still evolving. Thus, when confronted with a worn total knee implant
      and developing osteolysis, the surgeon should consider each of these factors in
      selecting the best management option to eliminate the source of debris and
      minimize the potential for wear and osteolysis following revision.

PMID- 17213383
TI  - Hindfoot arthrodesis.

PMID- 17213385
TI  - Overexpression of angiopoietin-like protein 4 alters mitochondria activities and
      modulates methionine metabolic cycle in the liver tissues of db/db diabetic mice.
AB  - Angiopoietin-like protein 4 (ANGPTL4) is a circulating protein predominantly
      produced from fat tissue and liver. Recent data from others and our laboratory
      have demonstrated this protein to be an important player in energy metabolism and
      insulin sensitivity. However, the molecular mechanisms underlying its metabolic
      actions remain elusive. In this study, we have employed a two-dimensional
      fluorescence difference gel electrophoresis technique to study the protein
      profiles in the livers of db/db mice treated with or without ANGPTL4. When
      compared with those of lean mice, 118 proteins were found to be up- or down
      regulated in db/db mice. Adenovirus-mediated overexpression of ANGPTL4 could
      reverse a large portion of the up- or down-regulated proteins to control levels.
      Especially, a number of mitochondria proteins were down-regulated by ANGPTL4 to a
      great extent. Chronic treatment with ANGPTL4 resulted in an elevated activity of
      mitochondria respiratory chain complexes II-III and IV in db/db mice.
      Additionally, several key enzymes in the methionine/homocysteine metabolic cycle
      were found to be increased in db/db diabetic mice but decreased by ANGPTL4
      treatment. HPLC analysis consistently revealed that ANGPTL4 could significantly
      restore the augmented S-adenosylmethionine levels and S-adenosylmethionine/S
      adenosylhomocysteine ratios in livers of db/db mice. In summary, our results
      suggest that ANGPTL4 might elicit its metabolic effects through modulating the
      mitochondria functions and methionine metabolic cycles in the liver tissue.

PMID- 17213386
TI  - Transcriptional regulation of the cholesterol side chain cleavage cytochrome P450
      gene (CYP11A1) revisited: binding of GATA, cyclic adenosine 3',5'-monophosphate
      response element-binding protein and activating protein (AP)-1 proteins to a
      distal novel cluster of cis-regulatory elements potentiates AP-2 and
      steroidogenic factor-1-dependent gene expression in the rodent placenta and
      ovary.
AB  - The first and key enzyme controlling the synthesis of steroid hormones is
      cholesterol side chain cleavage cytochrome P450 (P450scc, CYP11A1). This study
      sought to elucidate overlooked modes of regulation of P450scc transcription in
      the rodent placenta and ovary. Transcription of P450scc requires two clusters of
      cis-regulatory elements: a proximal element (-40) known to bind either activating
      protein 2 (AP-2) in the placenta, or steroidogenic factor 1 in the ovary, and a
      distal region of the promoter (-475/-447) necessary for potentiation of the AP
      2/steroidogenic factor 1-dependent activity up to 7-fold. In primary cultures of
      mouse trophoblast giant cells and rat ovarian granulosa cells, binding of trans
      factors to the distal regulatory sequences generated transcriptional activity in
      a tissue-specific pattern: in the placenta, cAMP response element (CRE)-binding
      protein 1 (CREB-1) and GATA-2 binding generates promoter activity in a cAMP
      independent manner, whereas in ovarian cells, CREB-1 and GATA-4 are required for
      FSH responsiveness. However, as ovarian follicles advance toward ovulation,
      elevated Fra-2 expression replaces CREB-1 function by binding the same CRE(1/2)
      motif. Our findings suggest that upon onset of follicular recruitment, CREB-1
      mediates FSH/cAMP signaling, which switches to cAMP-independent expression of
      P450scc in luteinizing granulosa cells expressing Fra-2. In the placenta, the
      indispensable role of CREB-1 was demonstrated by use of dominant-negative CREB-1
      mutant, but neither cAMP nor Ser133 phosphorylation of CREB-1 is required for
      P450scc transcription. These observations suggest that placental regulation of
      P450scc expression is subjected to alternative signaling pathway(s) yet to be
      found.

PMID- 17213387
TI  - The cover. The battery.

PMID- 17213388
TI  - Researchers probe lupus causes, treatments.

PMID- 17213389
TI  - Ham radio gives physicians long reach.

PMID- 17213390
TI  - Death not necessarily end for heart devices.

PMID- 17213391
TI  - Precautions, skills key for child sedation.

PMID- 17213392
TI  - Wait-and-see prescription for acute otitis media.

PMID- 17213393
TI  - Survival in women after diagnosis of lung cancer.

PMID- 17213394
TI  - Survival in women after diagnosis of lung cancer.

PMID- 17213395
TI  - Rapid response team responses.

PMID- 17213396
TI  - Rapid response team responses.

PMID- 17213397
TI  - A word from our moderator.

PMID- 17213398
TI  - A word from our moderator.

PMID- 17213399
TI  - Psychosocial aspects of HIV treatment.

PMID- 17213401
TI  - Relationship between adherence to evidence-based pharmacotherapy and long-term
      mortality after acute myocardial infarction.
AB  - CONTEXT: The extent to which drug adherence may affect survival remains unclear,
      in part because mortality differences may be attributable to "healthy adherer"
      behavioral attributes more so than to pharmacological benefits. OBJECTIVE: To
      explore the relationship between drug adherence and mortality in survivors of
      acute myocardial infarction (AMI). DESIGN, SETTING, AND PARTICIPANTS: Population
      based, observational, longitudinal study of 31 455 elderly AMI survivors between
      1999 and 2003 in Ontario. All patients filled a prescription for statins, beta
      blockers, or calcium channel blockers, with the latter drug considered a control
      given the absence of clinical trial-proven survival benefits. MAIN OUTCOME
      MEASURES: Patient adherence was subdivided a priori into 3 categories--high
      (proportion of days covered, > or =80%), intermediate (proportion of days
      covered, 40%-79%), and low (proportion of days covered, <40%)--and compared with
      long-term mortality (median of 2.4 years of follow-up) using multivariable
      survival models (and propensity analyses) adjusted for sociodemographic factors,
      illness severity, comorbidities, and concomitant use of evidence-based therapies.
      RESULTS: Among statin users, compared with their high-adherence counterparts, the
      risk of mortality was greatest for low adherers (deaths in 261/1071 (24%) vs
      2310/14,345 (16%); adjusted hazard ratio, 1.25; 95% confidence interval, 1.09
      1.42; P = .001) and was intermediary for intermediate adherers (deaths in
      472/2407 (20%); adjusted hazard ratio, 1.12; 95% confidence interval, 1.01-1.25;
      P = .03). A similar but less pronounced dose-response-type adherence-mortality
      association was observed for beta-blockers. Mortality was not associated with
      adherence to calcium channel blockers. Moreover, sensitivity analyses
      demonstrated no relationships between drug adherence and cancer-related
      admissions, outcomes for which biological plausibility do not exist. CONCLUSION:
      The long-term survival advantages associated with improved drug adherence after
      AMI appear to be class-specific, suggesting that adherence outcome benefits are
      mediated by drug effects and do not merely reflect an epiphenomenon of "healthy
      adherer" behavioral attributes.

PMID- 17213400
TI  - N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP),
      cardiovascular events, and mortality in patients with stable coronary heart
      disease.
AB  - CONTEXT: Identification of individuals at high risk for cardiovascular events is
      important for the optimal use of primary and secondary prevention measures.
      OBJECTIVE: To determine whether plasma levels of amino terminal fragment of the
      prohormone brain-type natriuretic peptide (NT-proBNP) predict cardiovascular
      events or death independent of other available prognostic tests. DESIGN, SETTING,
      AND PARTICIPANTS: Prospective cohort study (2000-2002) of 987 individuals in
      California with stable coronary heart disease in the Heart and Soul Study, who
      were followed up for a mean of 3.7 (range, 0.1-5.3) years. MAIN OUTCOME MEASURES:
      The association of baseline NT-proBNP levels with death or cardiovascular events
      (myocardial infarction, stroke, or heart failure). Traditional clinical risk
      factors, echocardiographic measures, ischemia, other biomarkers, and New York
      Heart Association classification were adjusted for to determine whether NT-proBNP
      levels were independent of other prognostic factors. Receiver operating
      characteristic (ROC) curves were used to assess the incremental prognostic value
      of adding NT-proBNP level to these other measures. RESULTS: A total of 256
      participants (26.2%) had a cardiovascular event or died. Each increasing quartile
      of NT-proBNP level (range of quartile 1, 8.06-73.95 pg/mL; quartile 2, 74-174.5
      pg/mL; quartile 3, 175.1-459 pg/mL; quartile 4, > or =460 pg/mL) was associated
      with a greater risk of cardiovascular events or death, ranging from 23 of 247
      (annual event rate, 2.6%) in the lowest quartile to 134 of 246 (annual event
      rate, 19.6%) in the highest quartile (unadjusted hazard ratio [HR] for quartile 4
      vs quartile 1, 7.8; 95% confidence interval [CI], 5.0-12.1; P<.001). Each SD
      increase in log NT-proBNP level (1.3 pg/mL) was associated with a 2.3-fold
      increased rate of adverse cardiovascular outcomes (unadjusted HR, 2.3; 95% CI,
      2.0-2.6; P<.001), and this association persisted after adjustment for all of the
      other prognostic measures (adjusted HR, 1.7; 95% CI, 1.3-2.2; P<.001). The
      addition of NT-proBNP level to standard clinical assessment and complete
      echocardiographic parameters significantly improved the area under the ROC curves
      for predicting subsequent adverse cardiovascular outcomes (0.80 for clinical risk
      factors and echocardiographic parameters plus log NT-proBNP vs 0.76 for clinical
      risk factors and echocardiographic parameters only; P = .006). CONCLUSIONS:
      Elevated levels of NT-proBNP predict cardiovascular morbidity and mortality,
      independent of other prognostic markers, and identify at-risk individuals even in
      the absence of systolic or diastolic dysfunction by echocardiography. Level of NT
      proBNP may help guide risk stratification of high-risk individuals, such as those
      with coronary heart disease.

PMID- 17213402
TI  - Microenvironmental genomic alterations and clinicopathological behavior in head
      and neck squamous cell carcinoma.
AB  - CONTEXT: Carcinogens associated with head and neck squamous cell carcinoma (SCC)
      genesis should inflict genomic alterations not only on the epithelium but also
      the mesenchyme of the aerodigestive tract. Therefore, the apparently nonmalignant
      stroma surrounding the tumor epithelium can acquire genomic alterations and
      contribute to cancer initiation and progression. OBJECTIVES: To determine
      compartment-specific loci of loss of heterozygosity or allelic imbalance (LOH/AI)
      and to identify which genomic alterations restricted to the stroma cell
      population contribute to aggressiveness of head and neck SCC disease. DESIGN,
      SETTING, AND PATIENTS: Tumor epithelium and surrounding stroma were isolated from
      122 US patients with oral cavity and oropharyngeal or hypopharyngeal SCC and
      subjected to whole-genome LOH/AI analysis using 366 microsatellite markers.
      Samples, collected between 2001 and 2004, were pulled and transferred in batches
      of 10 to 30 between 2002 and 2005. Laser capture microdissection DNA extraction
      and technical genotyping occurred on a rolling model between 2002 and November
      2005. MAIN OUTCOME MEASURES: Compartment-specific frequency and distribution of
      LOH/AI were determined, and hot spots of genomic alterations identified.
      Compartment-specific LOH/AI events were correlated with presenting
      clinicopathologic characteristics. RESULTS: Tumor-associated stroma of head and
      neck SCC from smokers were found to have a high degree of genomic alterations. A
      correlation between tumor aggressiveness could be found for a specific set of 5
      loci. Three stroma-specific loci (D4S2417, D3S360, and D19555) were associated
      with tumor size (pT) and regional nodal metastases (pN). Furthermore, 2
      epithelial-specific LOH/AI hot spots were positively correlated with pN status
      and clinical stage. CONCLUSIONS: Stroma-specific genetic alterations are
      associated with smoking-related head and neck SCC genesis. These findings suggest
      novel prognostic or diagnostic biomarkers and identify potential new molecular
      targets for therapeutic and preventive intervention.

PMID- 17213403
TI  - A 74-year-old woman with diabetes.
AB  - Ms M, a 74-year-old woman with type 2 diabetes of 6 years' duration, has a
      glycated hemoglobin (HbA1C) value of 7.4% despite taking 3 oral antidiabetic
      medications, as well as coexistent hypertension and abdominal obesity. She has no
      known microvascular or macrovascular complications of diabetes and is otherwise
      healthy. She is reluctant to commence insulin treatment as she dislikes the idea
      of injections and wonders if there are any alternate options if she is to get her
      HbA(1C) value below 7%. The natural history of type 2 diabetes, reasons why many
      patients begin requiring insulin over time, rationale for tight glycemic control,
      and therapeutic options for Ms M are discussed.

PMID- 17213404
TI  - A new era of unapproved drugs: the case of Abigail Alliance v Von Eschenbach.

PMID- 17213405
TI  - Does clopidogrel each day keep stent thrombosis away?

PMID- 17213406
TI  - Natriuretic peptides and cardiovascular events: more than a stretch.

PMID- 17213407
TI  - JAMA patient page. Insulin.

PMID- 17213408
TI  - Known-groups analysis of the harris infant neuromotor test.
AB  - BACKGROUND AND PURPOSE: The Harris Infant Neuromotor Test (HINT) is a screening
      tool designed to identify neuromotor or cognitive/behavioral concerns in infants
      who are healthy or at high risk between the ages of 3 and 12 months. The purpose
      of this study was to determine whether the HINT could distinguish between infants
      at high risk and infants at low risk for neuromotor delays. SUBJECTS AND METHODS:
      Following HINT administration by trained health care professionals, scores were
      compared for 54 high-risk infants and 412 low-risk infants with a t test.
      RESULTS: Mean HINT scores for infants at low risk were lower than mean scores for
      infants at high risk, as would be expected in that higher scores indicate higher
      risk. Significant differences were found at 4, 5, 7, and 8 months. At 6 months,
      there were no significant differences. There were not enough high-risk infants in
      other subgroups for reliable comparison. DISCUSSION AND CONCLUSION: The HINT
      appears to discriminate effectively between infants who are at low risk and
      infants who are at high risk for neuromotor delays, supporting the use of the
      HINT as a screening tool for infants in the first year of life.

PMID- 17213409
TI  - The influence of otolith dysfunction on the clinical presentation of people with
      a peripheral vestibular disorder.
AB  - BACKGROUND AND PURPOSE: Traditional vestibular function testing has measured
      horizontal semicircular canal function only. Otolith function tests have recently
      been developed, but their clinical significance has not been determined. The
      purpose of this study was to investigate the influence of otolith dysfunction on
      the clinical presentation of individuals with a peripheral vestibular disorder.
      SUBJECTS AND METHODS: Twenty-one subjects with loss of horizontal semicircular
      canal function only and 37 subjects with combined loss of horizontal semicircular
      canal and otolith organ function were recruited. All subjects received a
      comprehensive clinical assessment, including self-report questionnaires and
      measures of balance performance. RESULTS: No significant differences were
      identified between subjects with or without otolith dysfunction with respect to
      symptom severity, self-perceived handicap, functional limitations, or balance
      performance. DISCUSSION AND CONCLUSION: Otolith dysfunction does not
      significantly influence the clinical presentation of individuals with a
      peripheral vestibular disorder. Other factors, including symptom severity, may be
      more influential.

PMID- 17213410
TI  - Cortical reorganization following bimanual training and somatosensory stimulation
      in cervical spinal cord injury: a case report.
AB  - BACKGROUND AND PURPOSE: Deficits in upper-extremity function in individuals with
      tetraplegia are primarily due to the loss of motor pathways. Detrimental cortical
      reorganization, however, may create further loss of function. The purpose of this
      case report is to describe the cortical changes associated with a combination
      intervention using bimanual massed practice training with somatosensory
      stimulation. CASE DESCRIPTION: "BR" was a 22-year-old man with C6 tetraplegia and
      hand impairment who participated in this training intervention for 3 weeks.
      OUTCOMES: BR demonstrated improvements in sensory function, strength (the force
      generating capacity of muscle), and performance of functional hand skills.
      Following the training, the cortical motor map of the biceps brachii muscle
      shifted anteriorly and increased in area and volume. DISCUSSION: This is the
      first documented case in which changes in the size and location of the cortical
      map were associated with an intervention and improvement in function in an
      individual with tetraplegia. This case suggests that an intensive training
      intervention may induce both functional and neurophysiological changes.

PMID- 17213411
TI  - Management of stress urinary incontinence with surface electromyography-assisted
      biofeedback in women of reproductive age.
AB  - BACKGROUND AND PURPOSE: Although surgery has been widely accepted as the
      treatment of choice for stress urinary incontinence (SUI), there has recently
      been an increased interest in the conservative management of this condition. The
      aims of this study were to test the ability of a biofeedback-assisted pelvic
      floor muscle exercise (PFME) program to affect symptoms of SUI in premenopausal
      women and to evaluate a training program that might lead to successful outcomes
      in a relatively limited number of sessions. SUBJECTS: Twenty-six women with SUI
      were treated with PFME with surface electromyography (sEMG)-assisted biofeedback.
      All participants were of reproductive age and were treated individually for 12
      sessions. METHODS: results were evaluated with a 7-day voiding diary, a 1-hour
      pad test, pelvic-floor muscle strength measurements, sEMG amplitudes, a leakage
      index, and a quality-of-life questionnaire. These variables were compared before
      and after the intervention. RESULTS: The frequency of urine loss, the occurrence
      of nocturia, and the number of pads required decreased significantly after the
      intervention. Objective cure was found in 61.5% of women. There was a significant
      improvement in the quality of life, in pelvic-floor muscle strength, and in the
      sEMG amplitudes of all contractions throughout the intervention. DISCUSSION AND
      CONCLUSION: A relatively short-term intervention of PFME with sEMG-assisted
      biofeedback appeared to be helpful in relieving symptoms of SUI in premenopausal
      women and represents a reasonable conservative management option.

PMID- 17213412
TI  - The importance of being earnest--about disk nomenclature.

PMID- 17213413
TI  - Neuro-ophthalmology for neuroradiologists.
AB  - Combining an understanding of neuro-ophthalmologic anatomy with proper imaging
      techniques provides a powerful method to detect lesions involving the afferent
      and efferent visual pathways. Precise documentation of the extent of injury
      within the nervous system is becoming increasingly important to assess and
      monitor the effect of neurologic therapies. This review will focus on those
      common neuro-ophthalmologic problems that have exquisite localizing value on
      neuro-imaging.

PMID- 17213414
TI  - Angiography of primary central nervous system angiitis of childhood: conventional
      angiography versus magnetic resonance angiography at presentation.
AB  - BACKGROUND AND PURPOSE: To systematically analyze conventional angiographic (CA)
      features of children with primary central nervous system angiitis (cPACNS), to
      compare and correlate CA and MR angiography (MRA) lesion characteristics, and to
      define the sensitivity and specificity of MRA with CA as a reference standard.
      METHODS: A retrospective, single-center cohort study of consecutive patients with
      cPACNS was performed. Patients with CA and MRA studies at diagnosis were
      included. Imaging studies were blindly reviewed by 2 neuroradiologists using a
      standard analysis protocol. CA and MRA studies were compared using nonparametric
      analysis. RESULTS: Of 45 patients with MRA at diagnosis, there were 25 for whom
      CA and MRA studies were performed within 1 month of each other. These comprised
      the study group. The CA distribution of lesions was multifocal (76%) and proximal
      (86%) (P < .05) with a trend toward unilaterality (P = .06) with anterior
      circulation involvement (P = .08). The sensitivity and specificity of MRA for CA
      abnormality was 70% and 98%, respectively. There was no significant difference
      between MRA and CA for lesion detection or characterization (P = .87), and the
      modalities showed a fair correlation (kappa = 0.4). CONCLUSION: Angiographic
      lesions are multifocal and occur proximally and unilaterally within the anterior
      circulation. There is no significant difference in the ability of MRA to detect
      and characterize lesions when compared with CA.

PMID- 17213415
TI  - Involvement of the anterior lobe of the cerebellar vermis in perinatal profound
      hypoxia.
AB  - BACKGROUND AND PURPOSE: We report abnormal high T2 signal intensity in the
      anterior lobe of the cerebellar vermis that we believe was the result of profound
      hypoxic ischemic encephalopathy in the perinatal period in term infants. We
      tested the hypothesis that this sign was associated with other signs of
      significant perinatal hypoxic damage. METHODS: Thirty patients with clinically
      and radiologically confirmed perinatal profound hypoxia close to term were
      included in the study. The cranial MR images were reviewed by 2 pediatric
      neuroradiologists and were scored for the presence and severity of
      hypoxia/ischemia in the regions typically affected by profound hypoxia. The
      presence or absence of high T2 signal intensity in the vermis and other sites was
      correlated with the extent of damage in typically affected regions. RESULTS:
      Eighteen of 30 patients had high T2 signal intensity in the vermis. The presence
      of vermian damage correlated positively with radiologic evidence of severe
      hypoxic damage and extremely poor (0 or 1) 1-minute Apgar scores. CONCLUSIONS:
      High T2 signal intensity in the anterior lobe of the vermis probably represents
      gliosis secondary to hypoxia/ischemia and is related to the severity of damage in
      the term infant.

PMID- 17213416
TI  - Selective vulnerability and the cerebellum in neonates.

PMID- 17213417
TI  - Anomalous intracranial venous drainage associated with basal ganglia
      calcification.
AB  - We describe the neuroradiologic findings in a 7-year-old boy with anomalous
      intracranial venous drainage and cerebral calcification. CT scans demonstrated
      that his scalp mass was a plexus of scalp veins filled through the emissary
      foramen, and there were cerebral calcifications. Angiography revealed bilateral
      sigmoid sinus atresia with most of the intracranial venous drainage via the
      prominent mastoid emissary veins into dilated scalp vein. The possible
      relationship between cerebral calcification and anomalous intracranial venous
      drainage is discussed.

PMID- 17213419
TI  - Lingual hamartoma in an infant: CT and MR imaging.
AB  - Lingual hamartoma is a rare tongue mass, primarily diagnosed in childhood. In
      most cases in the literature, the masses were surgically removed without
      preoperative imaging. There are only 3 cases reported in the clinical literature
      that describe preoperative imaging findings. We report the clinical and imaging
      findings in an infant with lingual hamartoma and review the literature.

PMID- 17213418
TI  - Intracranial infantile hemangiomas associated with PHACE syndrome.
AB  - BACKGROUND AND PURPOSE: Head and neck infantile hemangiomas are common lesions
      that are rarely observed in an intracranial location. We report 4 patients with
      orbital infantile hemangiomas and ipsilateral enhancing intracranial lesions,
      presumed to be infantile hemangiomas. METHODS: Imaging studies and medical
      records of 4 infants with orbital hemangiomas and enhancing intracranial lesions
      were reviewed. The intracranial lesions were evaluated in terms of their
      location, signal intensity characteristics, enhancement pattern, and degree of
      involution following treatment. Additional findings associated with PHACE
      syndrome were also noted and a literature review of intracranial infantile
      hemangiomas and PHACE syndrome was also performed. RESULTS: The intracranial
      masses were primarily in or adjacent to the internal auditory canal and
      demonstrated imaging characteristics and treatment response similar to the
      ipsilateral orbital lesions. Ipsilateral internal carotid artery hypoplasia,
      ipsilateral cerebellar hemisphere hypoplasia, and/or other head and neck
      hemangiomas were present in all patients. CONCLUSION: These cases collectively
      support the diagnosis of intracranial infantile hemangiomas and suggest a unique
      radiographic association between PHACE syndrome and intracranial infantile
      hemangiomas.

PMID- 17213420
TI  - Which MR imaging sequences are necessary in determining the need for radiation
      therapy for cord compression? A prospective study.
AB  - BACKGROUND AND PURPOSE: To determine which MR imaging sequences are necessary to
      assess for spinal metastases. METHODS: Hypothetical MR imaging interpretations
      and management plans were made prospectively for consecutive adult cases acquired
      retrospectively. Standardized MR imaging protocols were independently interpreted
      by 2 neuroradiologists. MR imaging protocol types varied: 1) T1-weighted images
      only; 2) T1-weighted and T2-weighted images; 3) T1-weighted and postcontrast T1
      weighted images; and 4) T1- and T2-weighted images and postcontrast T1-weighted
      images. Hypothetical management plans were created by 2 radiation oncologists.
      Logit model was used to investigate the effect of MR imaging protocol type on the
      probability of recommending radiation therapy (RT). Mixed effect models were used
      to investigate whether median spinal level or total number of spinal levels of
      planned RT was associated with MR imaging protocol type. RESULTS: Thirty-one
      subjects were evaluated, each with multiple scan interpretations. Logit model
      showed that neither MR imaging protocol type nor neuroradiologist reader affected
      the probability that the oncologist would recommend RT (all P > .50). Mixed
      models showed that neither ML nor NL was affected by MR imaging protocol type or
      by neuroradiologist reader (all P > .12). CONCLUSION: Although MR imaging is
      known to be the most useful diagnostic test in suspected spinal cord compression,
      which particular MR images are necessary remain unclear. Compared with T1
      weighted images alone, the additional use of T2-weighted and/or postcontrast T1
      weighted sequences did not significantly affect the probability that RT would be
      recommended or the levels that would be chosen for RT in our study. Our data
      suggest that unenhanced T1-weighted images may be sufficient for evaluation of
      possible cord compression.

PMID- 17213421
TI  - Sacroplasty by CT and fluoroscopic guidance: is the procedure right for your
      patient?
AB  - BACKGROUND AND PURPOSE: Sacral insufficiency fractures are an infrequent but
      often disabling cause of severe low back pain. We report our results of a
      sacroplasty technique, using CT for needle placement and fluoroscopy to monitor
      the polymethylmethacrylate injection in a group of patients with sacral
      insufficiency fractures. METHODS: All patients had a history of chronic back pain
      and had an osteoporotic sacral insufficiency fracture documented by imaging
      before the procedure. With the patient under conscious sedation, a bone biopsy
      needle was placed under CT guidance; the patient was then transferred to the
      fluoroscopy suite, where a polymethylmethacrylate mixture was injected into the
      sacrum under real-time fluoroscopy. Clinical outcome was assessed by telephone.
      RESULTS: The procedure was performed on 13 female patients with an average age of
      76 years (range, 60-88 years). A bilateral procedure was performed in 11 patients
      and a unilateral procedure was performed in 2 patients. An average of 4.1 mL of
      cement was injected for each treatment. There were no instances of cement
      extravasation into the central canal or sacral foramina. Long-term follow-up,
      averaging 15 months, was available in 6 patients. Five patients (83%) reported no
      symptoms of pain at all. The final patient, in whom a bilateral procedure was
      performed, was completely asymptomatic on the left side but reported persistent
      unilateral pain on the right. CONCLUSION: Sacroplasty is a safe and effective
      procedure in the treatment of sacral insufficiency fractures that can provide
      substantial pain relief and lead to a better quality of life.

PMID- 17213422
TI  - Vertebral osteonecrosis: MR imaging findings and related changes on adjacent
      levels.
AB  - BACKGROUND AND PURPOSE: No prior report has comprehensively discussed the
      intravertebral vacuum cleft sign and the fluid sign on MR images of vertebral
      osteonecrosis. The purpose of this study was to investigate MR images of
      osteonecrotic vertebral bodies and adjacent intervertebral disks and vertebral
      bodies. METHODS: We retrospectively reviewed MR images of patients with vertebral
      osteonecrosis. Affected vertebral bodies with osteonecrosis were defined as an
      avascular area (nonenhanced area on enhanced T1-weighted images) with collections
      of intravertebral fluid (hyperintense signal on T2-weighted images), air (signal
      void on all images), or both. The degree of vertebral collapse was classified as
      mild (>50%) or severe (<50%) preserved vertebral height. Changes in adjacent
      intervertebral disks or vertebral bodies 2 above and 2 below the affected
      vertebrae were compared. RESULTS: We enrolled 112 patients (30 men, 82 women; 121
      vertebral bodies) in our study. Intravertebral air alone was observed in 48
      involved levels (39.7%), intravertebral fluid alone was found in 47 (38.8%), and
      both coexisted in 26 (21.5%). Degree of vertebral collapse in affected vertebral
      bodies significantly differed with presence of air or fluid (P < .05). Vertebral
      compression fractures adjacent to the affected vertebral bodies were more common
      in those with intravertebral air alone than in those with intravertebral fluid
      alone (P < .05). CONCLUSION: Vertebral collapse was more advanced and adjacent
      vertebral compression fractures were more frequent in patients with
      intravertebral air than in those with intravertebral fluid.

PMID- 17213423
TI  - High-resolution vascular imaging of the rat spine using liposomal blood pool MR
      agent.
AB  - BACKGROUND AND PURPOSE: High-resolution, vascular MR imaging of the spine region
      in small animals poses several challenges. The small anatomic features,
      extravascular diffusion, and low signal-to-noise ratio limit the use of
      conventional contrast agents. We hypothesize that a long-circulating,
      intravascular liposomal-encapsulated MR contrast agent (liposomal-Gd) would
      facilitate visualization of small anatomic features of the perispinal vasculature
      not visible with conventional contrast agent (gadolinium-diethylene
      triaminepentaacetic acid [Gd-DTPA]). METHODS: In this study, high-resolution MR
      angiography of the spine region was performed in a rat model using a liposomal
      Gd, which is known to remain within the blood pool for an extended period. The
      imaging characteristics of this agent were compared with those of a conventional
      contrast agent, Gd-DTPA. RESULTS: The liposomal-Gd enabled acquisition of high
      quality angiograms with high signal-to-noise ratio. Several important vascular
      features, such as radicular arteries, posterior spinal vein, and epidural venous
      plexus were visualized in the angiograms obtained with the liposomal agent. The
      MR angiograms obtained with conventional Gd-DTPA did not demonstrate these
      vessels clearly because of marked extravascular soft-tissue enhancement that
      obscured the vasculature. CONCLUSIONS: This study demonstrates the potential
      benefit of long-circulating liposomal-Gd as a MR contrast agent for high
      resolution vascular imaging applications.

PMID- 17213424
TI  - Double inversion recovery brain imaging at 3T: diagnostic value in the detection
      of multiple sclerosis lesions.
AB  - BACKGROUND AND PURPOSE: To prospectively determine the sensitivity in the
      detection of multiple sclerosis (MS) lesions by using double inversion recovery
      (DIR), fluid-attenuated inversion recovery (FLAIR), and T2-weighted turbo spin
      echo (T2 TSE) MR imaging at 3T. METHODS: Seventeen patients presenting with a
      clinically isolated syndrome (CIS) suggestive of MS, 9 patients with definite MS,
      and 6 healthy control subjects were included. Imaging was performed on a 3T MR
      system using DIR, FLAIR, and T2 TSE sequences. Lesions were counted and
      classified according to 5 anatomic regions: infratentorial, periventricular, deep
      white matter, juxtacortical, and mixed white matter-gray matter. The sensitivity
      at DIR was compared with the corresponding sensitivity at FLAIR and T2 TSE
      sequence. The contrast between lesions and normal-appearing gray matter, normal
      appearing white matter, and CSF was determined for all sequences. RESULTS:
      Because of higher lesion-white matter contrast, the DIR showed a higher number of
      lesions compared with the FLAIR (7% gain, P = 0.04) and the T2 TSE (15% gain, P =
      0.01). The higher sensitivity was also significant for the infratentorial region
      compared with the FLAIR (56% gain, P = 0.02) and the T2 TSE (44% gain, P = 0.02).
      Compared with the FLAIR, no significant changes of the lesion load measurements
      were observed in the supratentorial brain: slightly higher numbers of
      periventricular and mixed gray matter-white matter lesions on the DIR were
      counterbalanced by a slightly reduced sensitivity regarding juxtacortical
      lesions. CONCLUSION: DIR brain imaging at 3T provides the highest sensitivity in
      the detection of MS lesions especially in the infratentorial region.

PMID- 17213425
TI  - Detection and characterization of intracranial aneurysms with 16-channel
      multidetector row CT angiography: a prospective comparison of volume-rendered
      images and digital subtraction angiography.
AB  - BACKGROUND AND PURPOSE: The aim of our study was to compare multidetector row CT
      angiography (MDCTA) with digital subtraction angiography (DSA) in the detection
      and characterization of intracranial aneurysms. MATERIALS AND METHODS: In our
      blinded prospective study, 85 patients with suspected intracranial aneurysm (47
      women, 38 men; age range, 19-83 years) underwent both 16-channel MDCTA and DSA.
      The MDCT angiograms were interpreted for the presence, location, size, ratio of
      the neck to the dome (N/D ratio), and lobularity of the aneurysms and
      relationship of the aneurysm with the adjacent arterial branches, by using volume
      rendering techniques. MDCTA and DSA images (reference standard) were interpreted
      by 2 independent readers, and the results were compared. RESULTS: A total of 93
      aneurysms were detected at DSA in 71 patients, whereas no aneurysms were detected
      in 14 patients. Compared with DSA, the overall sensitivity, specificity, and
      accuracy of MDCTA on a per-aneurysm basis were 92.5%, 93.3%, and 92.6%,
      respectively, for both independent readers. For aneurysms of <3 mm, however,
      MDCTA had a sensitivity of 74.1% for reader 1 and 77.8% for reader 2. There was
      excellent agreement between readers in the detection of aneurysms (kappa =
      0.822). In addition, MDCTA was also accurate in determining N/D ratio of
      aneurysms, aneurysm lobularity, and adjacent arterial branches. CONCLUSION: MDCTA
      is accurate in the detection and characterization of intracranial aneurysms and
      can be used as a reliable alternative imaging technique to DSA in selected cases.

PMID- 17213426
TI  - A preliminary report of brain edema in patients with uremia at first
      hemodialysis: evaluation by diffusion-weighted MR imaging.
AB  - BACKGROUND AND PURPOSE: The dynamics of brain-water content associated with
      hemodialysis in patients with severe azotemia remains obscure. To investigate
      whether either interstitial or cytotoxic edema is responsible for dialysis
      disequilibrium syndrome (DDS), we used diffusion-weighted MR imaging (DWI) to
      measure the apparent diffusion coefficient (ADC), which is sensitive for
      detecting tissue water dynamics. METHODS: Eight consecutive patients with end
      stage renal disease (ESRD) and blood urea nitrogen level of more than 100 mg/dL
      (160.9 +/- 53.1 mg/dL) were recruited. Conventional MR images, DWI, and clinical
      manifestations were obtained before and after the 1st hemodialysis. The ADC
      values were determined for regions of normal-appearing gray and white matter and
      for regions of hyperintensity of white matter on T2-weighted MR imaging. RESULTS:
      Foci of bright areas of white matter were found in all patients on T2-weighted
      images. The ADC values of the patients with ESRD, in white matter and gray matter
      before and after hemodialysis, were greater than those of the healthy controls (P
      < .005). Regarding the impact of hemodialysis, the ADC of frontal lobe white
      matter increased significantly after hemodialysis (1.09 +/- 0.11 versus 1.03 +/-
      0.11, P = .036). We did not find the specific area of brain edema reported in
      posterior leukoencephalopathy and the osmotic demyelination syndrome.
      CONCLUSIONS: These results suggest that severe azotemia in end stage renal
      disease leads to interstitial brain edema reflected as increased ADC, and the
      further increased ADC reflects that edema associated with 1st hemodialysis is
      interstitial rather than cytotoxic in nature.

PMID- 17213427
TI  - Reproducibility of the whole-brain N-acetylaspartate level across institutions,
      MR scanners, and field strengths.
AB  - BACKGROUND AND PURPOSE: Radiologic markers in multicenter trials are often
      confounded by different instrumentation used. Our goal was to estimate the
      variance of the global concentration of the neuronal cell marker N
      acetylaspartate (NAA) among research centers using MR imaging scanners of
      different models, from different manufacturers, and of different magnetic field
      strength. MATERIALS AND METHODS: Absolute millimolar amounts of whole-brain NAA
      (WBNAA) were quantified with nonlocalizing proton MR spectroscopy in the brains
      of 101 healthy subjects (53 women, 48 men) aged 16-59 years (mean, 34.2 years).
      Twenty-three were scanned at 1 institute in a 1.5T Siemens Vision; 31 from
      another institute were studied with a 1.5T Siemens SP63; 36 were scanned at a
      third institute (24 with a 1.5T Vision, 12 with a 3T Siemens Trio); and 11 were
      obtained at a fourth institute using a 4T GE Signa 5.x. The NAA amounts were
      quantified with phantom-replacement and divided by the brain volume, segmented
      from MR imaging, to yield the concentration, a metric independent of brain size
      suitable for cross-sectional comparison. RESULTS: The average WBNAA concentration
      among institutions was 12.2 +/- 1.2 mmol/L. The subjects' WBNAA distributions did
      not differ significantly (p > .237) among the 4 centers, regardless of scanner
      manufacturer, model, or field strength and irrespective of whether adjustments
      were made for age or sex. CONCLUSION: Absolute quantification against a standard
      makes the WBNAA concentration insensitive to the MR hardware used to acquire it.
      This important attribute renders it a robust surrogate marker for multicenter
      neurologic trials.

PMID- 17213428
TI  - Deep brain reversible encephalopathy: association with secondary antiphospholipid
      antibody syndrome.
AB  - We present a case of a patient with systemic lupus erythematosus and secondary
      antiphospholipid syndrome. The patient presented with acute right cerebellar
      infarction and clinical and imaging evidence of brain stem and bilateral thalamic
      encephalopathy that resolved completely.

PMID- 17213429
TI  - Proton spectroscopy and imaging at 3T in ataxia-telangiectasia.
AB  - BACKGROUND AND PURPOSE: Ataxia-telangiectasia (A-T) is an autosomal recessive
      disorder with characteristic neurodegeneration of the cerebellum. We used MR
      spectroscopy to test the hypothesis that cerebellar metabolism in A-T patients
      would be abnormal relative to healthy controls. METHODS: Twelve adults with A-T
      and 12 healthy control subjects underwent MR imaging and long-echo time (1)H-MR
      spectroscopy at 3T. Voxels were acquired in the region of the dentate nucleus of
      the cerebellum and in parietooccipital white matter, and ratios for N
      acetylaspartate (NAA), choline (Cho), and creatine (Cr) were calculated. RESULTS:
      All of the A-T patients showed marked cerebellar atrophy of the vermis and
      hemispheres. Two patients showed multiple small foci of hypointensity on T2*
      weighted images throughout their brain suggestive of capillary telangiectasia. A
      further 2 patients had single low-signal-intensity foci. One patient had a tumor,
      thought to be meningioma radiologically, that was not suspected clinically. No
      group differences were found in the cerebral spectra, but analysis of the
      cerebellum revealed significantly lower NAA/Cho and higher Cho/Cr ratios in the A
      T patients compared with the controls. There was no difference between groups for
      the NAA/Cr ratio. CONCLUSION: The findings suggest increased Cho signal intensity
      in the cerebellum of adult A-T patients. If this finding is shown through the
      course of the disease, it may assist in the differentiation of early A-T from
      other forms of ataxia and provide a marker for monitoring treatment efficacy.

PMID- 17213430
TI  - Neurosarcoidosis presenting as acute infarction on diffusion-weighted MR imaging:
      summary of radiologic findings.
AB  - A 36-year-old woman presented with acute-onset right lower extremity
      paresthesias, dysarthria, right facial droop, and right hemiparesis. CT and MR
      imaging of the brain revealed extensive white matter disease and left basal
      ganglia infarction with dural and leptomeningeal enhancement. Differential
      considerations included vasculitis, granulomatous disease, and neoplasm. Chest,
      abdomen, and pelvis CTs were normal. Right temporal lobe biopsy revealed
      noncaseating granulomatous inflammation consistent with neurosarcoidosis.

PMID- 17213431
TI  - Decreased thickness of primary motor cortex in primary lateral sclerosis.
AB  - BACKGROUND AND PURPOSE: Primary lateral sclerosis (PLS) is a rare form of motor
      neuron disease characterized by upper motor neuron dysfunction. Because
      pathologic examination has revealed a loss of neurons in the motor cortex of
      patients with PLS, we sought to confirm and extend this finding by using MR
      imaging to measure cortical thickness. METHODS: Seven patients with PLS and 7 age
      matched neurologically normal control subjects were examined with heavily T1
      weighted short-tau inversion recovery (STIR) MR imaging performed at 3T. Cortical
      thickness in the anterior and posterior banks of both the central and precentral
      sulci were measured. RESULTS: Primary motor cortex (M1) was significantly thinner
      in patients with PLS than M1 in healthy control subjects, measuring 2.32 +/- 0.21
      mm compared with 2.79 +/- 0.18 mm (P = .0008). Cortical thickness did not differ
      between the 2 groups for primary sensory cortex or for the anterior or posterior
      banks of the precentral sulcus. Therefore, loss of gray matter was specific to
      motor cortex. Although this difference was modest, cortical thickness
      discriminated between the 2 groups; only 1 PLS case was within the range of
      normal measurements. CONCLUSION: Decreased thickness of M1 on the anterior bank
      of the precentral sulcus in patients with PLS, demonstrable by MR imaging,
      indicates a selective loss of upper motor neurons in this disease. Measurements
      of cortical thickness by MR imaging may provide a useful biomarker for diagnosis
      and study of upper motor neuron diseases.

PMID- 17213432
TI  - Diffusion tensor fiber tractography of the optic radiation: analysis with 6-, 12
      , 40-, and 81-directional motion-probing gradients, a preliminary study.
AB  - BACKGROUND AND PURPOSE: Knowing the exact location of the optic radiation
      preoperatively is important for surgery of the temporal lobe. We hypothesized
      that a greater number of motion-probing gradients (MPGs) would provide better
      results of diffusion tensor (DT) fiber tractography of the optic radiation. To
      test this hypothesis, this study evaluated differences in DT fiber tractography
      of the optic radiation under different MPG settings. METHODS: DT images were
      obtained in 12 healthy volunteers (7 men, 5 women) with a mean age of 32 years
      (range, 22-45 years) by using a 3T MR imaging scanner with single-shot echo
      planar imaging with parallel acquisition (reduction factor = 2). MPG was applied
      in 6, 12, 40, and 81 independent directions. The first region of interest (ROI)
      was placed in the occipital lobe, and the second ROI was placed in the lateral
      geniculate body. Fibers penetrating both ROIs were considered as the optic
      radiation. Anteroposterior distance between the tip of the Meyer loop and the
      lateral geniculate body on an axial section was defined as a loop index. Numbers
      of fibers and loop indices in both cerebral hemispheres were evaluated
      statistically. RESULTS: The optic radiation was well visualized in full length by
      DT fiber tractography in 20 of 24 hemispheres (83%). No significant differences
      were noted in number of fibers and loop indices among different MPG settings.
      CONCLUSION: DT fiber tractography can frequently depict almost the entire optic
      radiation. MPG number does not exert any significant effect on visualization of
      the optic radiation, and 6-directional MPG is thus sufficient for this purpose.

PMID- 17213433
TI  - CT angiographic analysis of carotid artery stenosis: comparison of manual
      assessment, semiautomatic vessel analysis, and digital subtraction angiography.
AB  - BACKGROUND AND PURPOSE: To compare multisection CT angiography (CTA) analyzed
      with source/maximum intensity projection (MIP) images as well as semiautomated
      vessel analysis software with intra-arterial digital subtraction angiography
      (DSA) in detection and grading of carotid artery bifurcation stenosis. METHODS:
      Consecutive patients with sonography evidence of a marked internal carotid artery
      stenosis underwent both carotid CTA and DSA (37 patients, 73 vessels). In CTA,
      the grade of stenosis was determined using axial source and MIP images as well as
      vessel analysis. The scans were blind-analyzed by 2 neuroradiologists using the
      NASCET criteria. RESULTS: Correlation of CTA source/MIP images versus DSA
      estimates of stenosis (R = 0.95) was higher than for the vessel analysis method
      versus DSA (R = 0.89). Compared with DSA, CTA source/MIP images underestimated
      high (78.2% versus 86.4%, P < .05) and moderate grades of stenosis (57.3% versus
      63.1%, P < .05) to a lesser extent than the vessel analysis method (68.5% versus
      83.5% and 51.8% versus 63.1%, P < .05). For a high-grade stenosis, sensitivity
      and specificity of source/MIP image CTA were 75% and 96%, respectively, whereas
      for the vessel analysis method, they were 47% and 96%, respectively. For moderate
      stenosis, the source/MIP image CTA sensitivity and specificity were 88% and 82%,
      respectively, and for vessel analysis method, 62% and 82%, respectively. CTA
      detected all 4 occlusions. CONCLUSION: In evaluation of carotid stenosis, CTA
      provides an adequate, less invasive alternative with a high correlation to
      conventional DSA, though it tends to underestimate clinically relevant grades of
      stenosis. Its accuracy is not improved by semiautomated analysis. The data
      support the use of CTA in confirming carotid occlusion.

PMID- 17213434
TI  - Evaluation of carotid artery stenosis with multisection CT and MR imaging:
      influence of imaging modality and postprocessing.
AB  - BACKGROUND AND PURPOSE: We prospectively evaluated the influence of different
      imaging techniques (time-of-flight MR angiography [TOF-MRA], contrast-enhanced MR
      angiography [CE-MRA], multisection CT angiography [CTA]) and postprocessing
      methods (maximum intensity projection [MIP], multiplanar reformation [MPR]) on
      carotid artery stenosis grading. MATERIALS AND METHODS: Fifty patients (34 men,
      16 women) with symptomatic stenosis of the internal carotid artery were examined
      with a 16-section spiral CT and a 1.5T MR unit. Two MRA techniques were applied:
      3D-TOF and CE-MRA. MPR was used for postprocessing with all modalities; MIP was
      used only with MRA. Four readers measured and calculated the percentage diameter
      stenosis independently according to NASCET criteria. The Wilcoxon test was used
      to measure interobserver variability, and the Friedman test was used to test the
      null-hypothesis of equality of the modalities. RESULTS: The hypothesis for global
      equality was rejected (P < .001). TOF-MRA and CTA assessed with MPR showed the
      highest concordance (difference, 0.6%; confidence interval [CI], -3.0, 4.3%), and
      CE-MRA with MIP and CTA showed the lowest concordance in stenosis grading
      (difference, 7.0%; CI, 3.4, 10.6%). MPR resulted in lower degrees of stenosis
      than MIP for both MRA sequences, although not statistically significant (CE, 
      3.0%; CI, -6.6, 0.6%; TOF, -2.2%; CI, -5.8, 1.4%). When only studies with good or
      excellent image quality were considered, the differences decreased, but the
      trends remained. CONCLUSION: Stenosis grading is dependent on the examination
      method and postprocessing technique. CTA and TOF-MRA evaluated with MPR revealed
      highest concordance.

PMID- 17213435
TI  - Physiologic and anatomic assessment of a canine carotid artery stenosis model
      utilizing phase contrast with vastly undersampled isotropic projection imaging.
AB  - BACKGROUND AND PURPOSE: Noninvasive assessment of the hemodynamic significance of
      carotid stenosis is often performed with MR angiography and supplemented with
      carotid Doppler sonography. Phase contrast with vastly undersampled isotropic
      projection reconstruction (PC-VIPR), a novel MR imaging technique, accelerates
      phase-contrast MR flow imaging and provides both images of the vessels and
      measurements of blood-flow velocities. For this study, we determined the accuracy
      of PC-VIPR blood-flow velocity measurements to determine pressure gradients
      across an experimental carotid stenosis. MATERIALS AND METHODS: A focal stenosis
      was surgically created in each common carotid artery of 6 canines. Digital
      subtraction angiography (DSA) was performed, and the degree of stenosis was
      determined using the North American Symptomatic Carotid Endarterectomy Trial
      methodology. A microcatheter was positioned in the carotid artery proximal and
      distal to the stenosis, and pressures were measured in the vessel through the
      catheter. PC-VIPR was then performed on a 1.5T MR imaging scanner with parameters
      producing 0.8-mm isotropic voxel resolution. From the velocity measurements,
      pressure gradients were calculated from the Navier-Stokes relationship to compare
      with the pressures measured by a catheter. RESULTS: Carotid stenoses in the 50%
      85% range were produced in the 12 arteries. Pressure gradients across the
      stenoses ranged from 6 to 26 mm Hg. The pressure gradient calculated from the PC
      VIPR data correlated (r = 0.91, P < .0001) with the actual pressure measurements.
      CONCLUSION: With PC-VIPR, a novel MR imaging technique, the hemodynamic effect of
      a stenosis on flow and pressure can be evaluated.

PMID- 17213436
TI  - Apparent diffusion coefficient mapping of salivary gland tumors: prediction of
      the benignancy and malignancy.
AB  - BACKGROUND AND PURPOSE: Preoperative prediction of tumor malignancy is clinically
      very important, because this information strongly influences the surgical plan.
      We evaluate the preoperative apparent diffusion coefficient (ADC) maps of benign
      and malignant salivary gland tumors. MATERIALS AND METHODS: High-resolution MR
      imaging was performed on 31 patients with benign or malignant salivary gland
      tumors; ADC maps of the tumors were also obtained. Surface coils of 47 or 110 mm
      diameter were used to improve the image resolution. The ADCs were compared with
      histologic features of the excised tumors. RESULTS: The ADC maps effectively
      depicted the histologic features of the salivary gland tumors, such as presence
      of cancer cells, myxomatous tissues, fibrosis, necrosis, cyst formation, and
      lymphoid tissues. The ADC maps showed that more frequent areas with high ADCs (>
      or = 1.8 x 10(-3) mm(2)/s) were significantly greater in benign tumors than in
      malignant tumors. The sensitivity and specificity for high ADC occupying fewer
      than 5% of the area of a tumor was 89% and 100%, respectively, resulting in 97%
      accuracy, 100% positive predictive value, and 96% negative predictive value.
      CONCLUSION: The ADC may provide preoperative tissue characterization of the
      salivary gland tumors.

PMID- 17213437
TI  - Plaque imaging of the internal carotid artery - correlation of B-flow imaging
      with histopathology.
AB  - BACKGROUND AND PURPOSE: The noninvasive identification of plaque types prone to
      cause symptomatic disease is of great interest to improve the effectiveness of
      surgical or interventional management. The purpose of the present prospective
      pilot study was to evaluate the association between the results of imaging-the
      novel sonography technique B-flow imaging (BFI), B-mode, and color Doppler
      imaging (CDI)-and histopathologic examination in the characterization of internal
      carotid artery (ICA) plaques. METHODS: Twenty-eight consecutive patients with
      high-grade internal carotid artery stenosis scheduled for carotid endarterectomy
      were included. BFI, B-mode, and CDI images were used to classify the plaques
      applying the standardized scores of Beletsky et al and the American Heart
      Association (AHA), to calculate the gray-scale median (GSM) and to detect
      potential ulcerations; histopathologic examination results of explanted plaques
      served as the "gold standard." RESULTS: Based on the classification of Beletsky
      et al, BFI and histopathologic examination results agreed in 21 (75%, kappa =
      0.61, P < .001) patients, and the corresponding results for B-mode were 19 (68%,
      kappa = 0.52, P < .001) patients, respectively. Corresponding results for the AHA
      classification revealed inferior agreements for BFI (19 patients/68%, kappa =
      0.38, P = .003) and B-mode (17 patients/61%, kappa = 0.25, P = .045). The median
      GSM for BFI and B-mode correlated significantly (r = 0.95, P < .001). The
      sensitivity of BFI for the detection of ulcerated plaques was 100% and the
      specificity was 95.8%; corresponding values for CDI were 100% and 92.7%,
      respectively. CONCLUSION: BFI and the combination of B-mode and CDI exhibit
      comparable results in the assessment of ICA plaque components and plaque
      ulceration as well as in the determination of GSM levels.

PMID- 17213438
TI  - Clear cell carcinoma of the base of the tongue: MR imaging findings.
AB  - Clear cell carcinoma of the base of the tongue is a rare minor salivary gland
      neoplasm, and to our knowledge, the MR imaging appearance of this entity has not
      been described. We present the MR imaging findings in such a case and review the
      differential diagnosis for tongue base masses in an adult.

PMID- 17213439
TI  - Primary intraosseous meningioma of the mandible: CT and MR imaging features.
AB  - We describe the rare entity of an intraosseous meningioma arising in the
      mandible. The meningioma was found incidentally in an asymptomatic adult patient
      on dental radiography, mimicking other cystic-appearing jaw masses. The CT and MR
      imaging features of mandibular meningioma are reviewed with reference to prior
      published descriptions of this unusual entity.

PMID- 17213440
TI  - Dental and facial bone abnormalities in pyknodysostosis: CT findings.
AB  - Pyknodysostosis is an autosomal-recessive disorder of osteoclast dysfunction
      causing osteosclerosis, with associated maxillofacial anomalies. Multidetector CT
      with multiplanar and 3D reconstruction illustrated the pathologic findings in
      this case. Abnormalities included multiple retained deciduous teeth, unerupted
      teeth with associated follicles, an irregularly expanded alveolus and body of the
      mandible, and an obtuse mandibular angle. Volume-rendered imaging better
      delineated the irregular dentition, with crowding and retention of deciduous
      teeth.

PMID- 17213441
TI  - Inflammatory myofibroblastic tumor of the nasal cavity.
AB  - Inflammatory myofibroblastic tumor (IMT) is a rare tumor with a variable natural
      history and biologic behavior, ranging from completely benign to malignant with
      fatal outcome. We report a case of benign IMT in the left nasal cavity with
      radiologic features mimicking angiofibroma. We also demonstrate the hypervascular
      nature of this disease on angiography and the contribution of preoperative
      embolization in assisting surgical excision and minimizing the potential
      uncontrolled intraoperative bleeding.

PMID- 17213442
TI  - Intracranial aspergillosis involving the internal auditory canal and inner ear in
      an immunocompetent patient.
AB  - We report the MR imaging findings in a case of intracranial aspergillosis
      involving the internal auditory canal (IAC) and inner ear in an immunocompetent
      patient. The presence of rim enhancement of the vestibulocochlear nerve, abnormal
      signal intensity involving the labyrinth, and adjacent meningeal enhancement
      might help clinicians to make a correct diagnosis in patients with a mass in the
      IAC and previous history of ear surgery.

PMID- 17213443
TI  - Optic tract hemorrhage after pituitary apoplexy.
AB  - Subarachnoid hemorrhage following pituitary apoplexy is rare, and optic tract
      hemorrhage after the apoplexy is extremely rare. We report a case of optic tract
      hemorrhage after apoplexy that is not associated with hematologic disorders.

PMID- 17213444
TI  - Reversible left hemispheric ischemia secondary to carotid compression in Eagle
      syndrome: surgical and CT angiographic correlation.
AB  - Symptoms of ipsilateral carotid artery compression secondary to an elongated
      styloid process or calcified stylohyoid ligament may be seen in Eagle syndrome.
      The patient will typically experience cervicofacial pain due to stimulation of
      the arterial nervous plexus. In addition, symptoms directly attributable to
      compression of the carotid artery may be seen, including visual symptoms and
      syncope. We report here the case of a patient who developed symptoms consistent
      with left hemispheric ischemia within 15 seconds of turning his head to the left.
      These symptoms were completely reversible on returning the head to the neutral
      position. No long-term sequelae were detected clinically or radiographically.

PMID- 17213446
TI  - HydroCoil for Endovascular Aneurysm Occlusion (HEAL) study: 3-6 month
      angiographic follow-up results.
AB  - BACKGROUND AND PURPOSE: The HydroCoil Embolic System (HES) was developed reduce
      recurrences of aneurysms relative to platinum coils. This study was conducted to
      evaluate the recurrence rate of cerebral aneurysms 3-6 months after treatment
      with HES. METHODS: We report the results in 135 cerebral aneurysms treated with
      HES in a prospective multicenter registry. Angiographic results 3-6 months after
      treatment were evaluated at a core laboratory. Wide variation in HES utilization
      within the HydroCoil for Endovascular Aneurysm Occlusion (HEAL) registry (HES
      representing 5% to 100% of the coil length used) allowed for subgroup analysis
      with regard to percentage length, last coil used, and packing attenuation in
      small (<10 mm) aneurysms. RESULTS: The overall recurrence rate was 38 (28.1%) of
      135, which included a number of large, giant, and previously recurrent aneurysms.
      When HES represented > or = 75% of coil length, the recurrence rate was 0 (0%) of
      18, whereas with <75% length of HES, the recurrence rate was 16 (23%) of 71 (P =
      .035). When the final coil deposited was a HES coil, the recurrence rate was 6
      (11%) of 53, whereas when the final coil was platinum, the recurrence rate was 10
      (29%) of 34 (P = .047). When the packing attenuation was > or = 50%, the
      recurrence rate was 11 (19%) of 59, whereas for packing attenuation <50%, the
      recurrence rate was 5 (18%) of 28. The packing attenuation calculations were very
      error-prone. CONCLUSION: Although the overall recurrence rates for small and
      large aneurysms in HEAL were no lower than published rates for aneurysms treated
      with platinum coils, patients treated in HEAL had a reduced recurrence rate when
      greater than 75% of the coil length used to treat an aneurysm was HES and when
      the final coil was HES.

PMID- 17213445
TI  - Treatment of unruptured intracranial aneurysms: a nationwide assessment of
      effectiveness.
AB  - BACKGROUND AND PURPOSE: With advances in neuroimaging, unruptured cerebral
      aneurysms are being diagnosed more frequently. Until 1995, surgical clipping of
      the aneurysm was the only treatment available. Since then, a less invasive
      endovascular technique has been found effective in a trial of ruptured aneurysms.
      No efficacy studies comparing the 2 procedures for unruptured aneurysms exist to
      guide clinical decisions. The objective of this study was to assess effectiveness
      and outcomes of endovascular versus neurosurgical treatment for unruptured
      intracranial aneurysms. METHODS: This was a retrospective cohort study, using
      data collected over a 1-year time interval (between 1998 and 2000), from 429
      hospitals, in 18 states, and representing 58% of the US population. A total of
      2535 treated, unruptured cerebral aneurysm cases were evaluated. The measurements
      used were effectiveness as measured by hospital discharge outcomes: 1) mortality
      (in-hospital death), 2) adverse outcomes (death or discharge to a rehabilitation
      or nursing facility), 3) length of stay, and 4) hospital charges. Univariate
      analyses compared endovascular versus neurosurgical discharge outcomes.
      Multivariable models were adjusted for age, sex, region, Medicaid insurance
      status, year, hospital case volume, comorbidity score, and admission source.
      RESULTS: Endovascular treatment was associated with fewer adverse outcomes (6.6%
      versus 13.2%), decreased mortality (0.9% versus 2.5%), shorter lengths of stay
      (4.5 versus 7.4 days), and lower hospital charges (42,044 dollars versus 47,567
      dollars) compared with neurosurgical treatment (P < .05). After multivariable
      adjustment, neurosurgical cases had 70% greater odds of an adverse outcome, 30%
      increased hospital charges, and 80% longer length of stay compared with
      endovascular cases (P < .05). CONCLUSIONS: The current analysis indicates that
      endovascular therapy is associated with significantly less morbidity, less
      mortality, and decreased hospital resource use at discharge, compared with
      conventional neurosurgical treatment for all unruptured aneurysms. Endovascular
      therapy, as a treatment alternative to surgical clipping, should be offered as a
      viable therapeutic option for all patients considering treatment of an unruptured
      cerebral aneurysm.

PMID- 17213447
TI  - Heparin-induced thrombocytopenia in a case of endovascular aneurysm coiling.
AB  - We report a case of 46-year-old man who underwent endovascular coil embolization
      for left anterior inferior cerebellar and posterior inferior cerebellar
      aneurysms. During embolization of both aneurysms, thrombotic complications were
      observed along with a relative lack of response to heparin. Intra-arterial
      abciximab was used to recanalize an almost completely occluded posterior inferior
      cerebellar artery. A marked decrease in platelet counts was found soon after
      embolization, which normalized within a few days. Serologic tests confirmed
      heparin-induced thrombocytopenia. This syndrome should be considered in cases
      with thromboembolic complications during endovascular procedures, particularly in
      patients undergoing repeated heparin exposure. A sudden decrease in platelet
      counts and lack of response to heparin, manifested as a relative lack of
      increasing activated clotting time, should make one suspect this syndrome.

PMID- 17213448
TI  - Intra-arterial thrombolysis for acute stroke in patients 80 and older: a
      comparison of results in patients younger than 80 years.
AB  - BACKGROUND AND PURPOSE: Intra-arterial fibrinolytic therapy is a promising
      treatment for acute ischemic stroke. Few data are available on its use in elderly
      patients. The purpose of this study was to compare the baseline characteristics,
      complications, and outcomes between intra-arterially treated ischemic stroke
      patients aged > or = 80 years and their younger counterparts. METHODS: Patients
      aged > or = 80 years (n = 33) were compared retrospectively with contemporaneous
      patients aged < 80 years (n = 81) from a registry of consecutive patients treated
      with intra-arterial thrombolysis over a 9-year period. RESULTS: The very elderly
      and younger cohorts were very similar in baseline characteristics, including
      pretreatment stroke severity (National Institutes of Health Stroke Scale [NIHSS]
      17 versus 16), differing only in history of stroke/transient ischemic attack (42%
      versus 22%, P = .01) and weight (66.8 versus 75.8 kg; P = .02). Significant
      differences in recanalization (TIMI 2-3) rates could not be detected between the
      very elderly and younger patients (79% versus 68%, P = .10). Rates of major
      symptomatic hemorrhage (7% versus 8%) and any intracerebral hemorrhage (39%
      versus 37%) did not differ. Outcomes at 90 days showed lower rates of excellent
      functional outcome (mRS < or = 1, 26% versus 40%, P = .02) and survival (57%
      versus 80%, P = .01) among the very elderly. CONCLUSIONS: Intra-arterial
      fibrinolysis in the elderly can be accomplished with recanalization rates and
      hemorrhage rates equal to that in younger patients. Although mortality rates are
      higher and good functional outcomes are lower than in younger persons,
      nondisabling outcomes may be achieved in a quarter of patients. These findings
      suggest that the investigation and use of intra-arterial thrombolytic treatment
      in very elderly patients should not be avoided but pursued judiciously.

PMID- 17213449
TI  - Pretreatment ipsilateral regional cortical blood flow influences vessel
      recanalization in intra-arterial thrombolysis for MCA occlusion.
AB  - BACKGROUND AND PURPOSE: The aim of acute stroke interventions is to achieve
      recanalization of the target occluded artery. We sought to determine whether
      pretreatment cortical cerebral blood flow (CBF) was associated with vessel
      recanalization in patients undergoing intra-arterial therapy. METHODS: This is a
      retrospective analysis of patients who underwent a quantitative xenon CT blood
      flow study and were noted to have a documented M1 middle cerebral artery (MCA) or
      carotid terminus occlusion less than 6 hours from symptom onset between January
      1997 and April 2001. Twenty-three patients who underwent intra-arterial
      thrombolysis were included in the analysis. Univariate and multivariate analyses
      were performed to determine whether pretherapy CBF was correlated to the
      likelihood of recanalization. RESULTS: A total of 23 patients were studied in
      this analysis with a median age of 69 (range 32-81) and median National
      Institutes of Health Stroke Score of 19 (range, 8-22). Twelve patients (52%)
      underwent combined intravenous/intra-arterial therapy, and 11 patients (48%) were
      treated with intra-arterial thrombolytics alone. Successful vessel recanalization
      (Thrombolysis in Myocardial Infarction classification 2 or 3 flow) occurred in 13
      patients (57%). The only variable associated with recanalization in multivariate
      modeling was mean ipsilateral MCA CBF (odds ratio, 1.25; 95% confidence interval,
      1.01-1.54; P = .035). A receiver operating characteristic curve was generated,
      and a mean ipsilateral MCA CBF threshold of 18 mL/100 g/min was found to be the
      threshold for successful recanalization. CONCLUSIONS: Our study suggests that
      patients with higher mean ipsilateral MCA CBF are more likely to recanalize. The
      threshold for successful revascularization may be 18 mL/100 g/min. Further study
      is required to determine whether pretreatment CBF is related to recanalization
      success.

PMID- 17213450
TI  - Stenting and angioplasty of the symptomatic chronically occluded carotid artery.
AB  - Patients with hemodynamic impairment ipsilateral to a carotid occlusion are at a
      high risk of subsequent stroke, and currently 2 surgical options have been
      studied: extracranial-to-intracranial bypass and direct thromboendarterectomy. We
      report the successful revascularization of 2 symptomatic chronically occluded
      carotid arteries with stenting and angioplasty.

PMID- 17213451
TI  - Brain AVM embolization with Onyx.
AB  - BACKGROUND AND PURPOSE: To report the initial experience by using a new liquid
      embolic agent (Onyx) for embolization of brain arteriovenous malformations
      (AVMs). METHODS: Between May 2000 and December 2005, 44 patients with brain AVMs
      were embolized with Onyx. There were 18 women and 26 men with a mean age of 42.4
      years (median 44, range 14-71 years). Clinical presentation included seizures in
      26 patients (59%), hemorrhage from the AVM in 13 patients (30%), subarachnoid
      hemorrhage from a concomitant aneurysm in 3 patients (7%), visual disturbances in
      1 patient (2.3%), and in 1 patient (2.3%) the AVM was an incidental finding. Mean
      estimated size of the AVM was 3.9 cm (median 4, range 2-7 cm). RESULTS: In 44
      patients, 52 embolization procedures were performed with 138 feeding pedicles
      embolized, ranging from 1 to 7 per patient. Average estimated size reduction was
      75% (median 80%, range 40%-100%). Total obliteration was achieved in 7 AVMs
      (16%), and partial embolization was followed by surgery in 10 patients and by
      radiosurgery in 20 patients. Complications occurred in 6 patients, leading to
      death in 1 patient (mortality 2.3%) and to permanent disability in 2 patients
      (morbidity 4.6%). CONCLUSION: Onyx is feasible and safe in the embolization of
      brain AVMs. Complete obliteration can be achieved in small AVMs. Large AVMs can
      be adequately reduced in size for additional surgical or radiosurgical treatment.

PMID- 17213453
TI  - Complex curve microcatheters for berry aneurysm endovascular therapy.
AB  - By using images created with 3D rotational angiography or CT angiography as
      templates, it is possible to place anatomically correct curves on microcatheters,
      curves that reproduce the complex 3D vascular anatomy of individual patients.
      Catheters so curved conform to the anatomy of arteries leading to aneurysms and
      are less likely to be forced out of position as coil packing progresses.

PMID- 17213454
TI  - Carotid blowout syndrome in patients with head-and-neck cancers: reconstructive
      management by self-expandable stent-grafts.
AB  - BACKGROUND AND PURPOSE: Some reports of reconstructive management of carotid
      blowout syndrome (CBS) with stent-grafts are promising, but some are unfavorable.
      This study sought to evaluate the hemostatic efficacy, safety, and outcome of
      reconstructive, endovascular stent-graft placement in patients with head-and-neck
      cancers in association with CBS. METHODS: Eight patients with head-and-neck
      cancers with CBS were treated with self-expandable stent-grafts. We evaluated the
      initial hemostatic results, complications, and outcomes by assessing the clinical
      and imaging findings. RESULTS: Immediate hemostasis was achieved in all patients.
      Initial complications included stroke in 1 patient and asymptomatic thrombosis of
      the carotid artery in 2 patients. Delayed complications included rebleeding,
      delayed carotid thrombosis, and brain abscess formation. Rebleeding was noted in
      4 patients and was successfully managed with a second stent-graft and
      embolization in 2 of them. Delayed carotid thrombosis with follow-up after 3
      months was found in 3 patients, 1 of whom had associated brain abscesses.
      CONCLUSION: Although stent-grafts achieved immediate and initial hemostasis in
      patients with head-and-neck cancers and CBS, long-term safety, stent patency, and
      permanency of hemostasis appeared unfavorable. This treatment may be for
      temporary or emergency purposes rather than serving as a permanent measure. We
      suggest its applications in patients with acute CBS that precludes performance of
      an occlusion test, as well as when carotid occlusion poses an unusually high risk
      of neurologic morbidity. We also propose prophylactic antibiotic treatment and
      combined embolization of pathologic vascular feeders to improve outcomes.

PMID- 17213457
TI  - Exploring the relationship between senior management team culture and hospital
      performance.
AB  - The purpose of this study was to explore relationships between senior management
      team culture and organizational performance in English hospital organizations
      (NHS trusts [National Health Service]). We used an established culture-rating
      instrument, the Competing Values Framework, to assess senior management team
      culture. Organizational performance was assessed using a wide variety of
      routinely collected measures. Data were gathered from all English NHS acute
      hospital trusts, a total of 197 organizations. Multivariate econometric analyses
      were used to explore the associations between measures of culture and measures of
      performance using regressions, ANOVA, multinomial logit, and ordered probit.
      Organizational culture varied across hospital organizations, and at least some of
      this variation was associated in consistent and predictable ways with a variety
      of organizational characteristics and measures of performance. The findings
      provide particular support for a contingent relationship between culture and
      performance.

PMID- 17213456
TI  - Use of preventive maternal and child health services by Latina women: a review of
      published intervention studies.
AB  - Some health indicators for Latinos tend to be more positive than socioeconomic
      status would predict. Yet, Latina women and their young children use fewer
      preventive health services and have a higher incidence of preventable diseases
      than non-Hispanic whites. The Institute of Medicine recently called for
      intervention research among minority subgroups to end racial and ethnic
      disparities in health care. To help guide future intervention research, this
      article presents a critique and synthesis of the peer-reviewed literature on
      interventions that enroll Latina women into preventive reproductive health
      services (prenatal care, cervical cancer screening, and child immunizations).
      Results are presented according to three categories of interventions:
      improvements within formal health care settings, outreach through lay health
      advisors (promotoras) and media, and interventions combining these approaches. An
      agenda for intervention research is proposed for preventive-care use by this
      population.

PMID- 17213458
TI  - The impact of managed care on access to highly active antiretroviral therapy and
      on outcomes among Medicaid beneficiaries with AIDS.
AB  - Medicaid has promoted managed care plans (MCPs) to control health care costs for
      HIV-infected enrollees. This article examines the impact of MCP enrollment on use
      of highly active antiretroviral therapy (HAART), antiretroviral therapy (ARV),
      hospitalization, and death among Medicaid beneficiaries with AIDS. A
      retrospective longitudinal cohort study of 7,028 Medicaid beneficiaries with AIDS
      in California was conducted from 1999 to 2001. The impact of MCP enrollment was
      estimated using single-equation and bivariate probit models. Baseline HAART use
      was found to be significantly lower for beneficiaries in MCPs versus fee-for
      service (FFS). The effect was attenuated and not significant after correcting for
      selection bias. MCP enrollment was not associated with overall ARV use,
      mortality, or hospitalization. MCP enrollment does not substantially affect
      medication use or clinical outcomes. Before making changes to care delivery,
      policy makers should address the potential costs and benefits of MCP over FFS
      Medicaid for chronically ill beneficiaries.

PMID- 17213459
TI  - Survival advantage associated with treatment of injury at designated trauma
      centers: a bivariate probit model with instrumental variables.
AB  - This article analyzes the effectiveness of designated trauma centers in Florida
      concerning reduction in the mortality risk of severely injured trauma victims. A
      bivariate probit model is used to compute the differential impact of two
      alternative acute care treatment sites. The alternative sites are defined as (1)
      a nontrauma center (NC) or (2) a designated trauma center (DTC). An instrumental
      variables method was used to adjust for prehospital selection bias in addition to
      the influence of age, gender, race, risk of mortality, and type of injury.
      Treatment at a DTC was associated with a reduction of 0.13 in the probability of
      mortality.

PMID- 17213460
TI  - Differences in prescription drug use in HMO and self-insured health plans.
AB  - Using pharmacy benefits manager claims data, this study analyzed how cost
      management techniques including cost sharing affected enrollees in health
      maintenance organizations (HMOs) versus employer-sponsored fee-for-service plans.
      Because HMOs bear the risk of pharmaceutical costs and influence the prescribing
      practices of the physicians in their network, we expected different patterns of
      prescription use, such as proportionately more generic medications in HMOs. Also,
      because HMO physicians are likely to prescribe relatively more drugs for high
      severity conditions, HMO enrollee demand should be less price sensitive. The
      impact of cost sharing was found to be significantly less for HMOs. A 5-dollar
      increase in copayments decreased expenditures by 16 percent in fee-for-service
      plans but only by 1 percent in HMOs. Furthermore, when cost sharing was set at
      zero, HMO plans were found to have significantly fewer and cheaper medications,
      resulting in lower per-enrollee medication expenditures.

PMID- 17213461
TI  - Flow-dependent transport in a mathematical model of rat proximal tubule.
AB  - The mathematical model of rat proximal tubule has been extended to include
      calculation of microvillous torque and to incorporate torque-dependent solute
      transport in a compliant tubule. The torque calculation follows that of Du Z, Yan
      Q, Duan Y, Weinbaum S, Weinstein AM, and Wang T (Am J Physiol 290: F289-F296,
      2006). In the model calculations, torque-dependent scaling of luminal membrane
      transporter density [either as an ensemble or just type 3 Na(+)/H(+) exchanger
      (NHE3) alone] had a relatively small impact on overall Na(+) reabsorption and
      could produce a lethal derangement of cell volume; coordinated regulation of
      luminal and peritubular transporters was required to represent the overall impact
      of luminal flow on Na(+) reabsorption. When the magnitude of torque-dependent
      Na(+) reabsorption in the model agrees with that observed in mouse proximal
      tubules, the model tubule shows nearly perfect perfusion-absorption balance at
      high luminal perfusion rates, but enhanced sensitivity of reabsorption at low
      flow. With a slightly lower coefficient for torque-sensitive transporter
      insertion, perfusion-absorption balance in the model tubule is closer to
      observations in the rat over a broader range of inlet flows. In simulation of
      hyperglycemia, torque-dependent transport attenuated the diuretic effect and
      brought the model tubule into closer agreement with experimental observation in
      the rat. The model was also extended to represent finite rates of hydration and
      dehydration of CO(2) and H(2)CO(3). With carbonic anhydrase inhibition, torque
      dependent transport blunted the diuretic effect and enhanced the shift from
      paracellular to transcellular NaCl reabsorption. The new features of this model
      tubule are an important step toward simulation of glomerulotubular balance.

PMID- 17213462
TI  - Downregulation of vasopressin V2 receptor promoter activity via V1a receptor
      pathway.
AB  - Vasopressin V(1a) and V(2) receptors (V(1a)R and V(2)R, respectively) distribute
      in the collecting duct of the kidney. Although the function of V(2)R mediating
      the antidiuretic effect of AVP has been investigated in detail, the role of
      V(1a)R in the collecting ducts has not been elucidated. In the present study, we
      have investigated the role of the V(1a)R pathway in V(2)R promoter activity. We
      cloned the 5'-flanking region of rat V(2)R (rV(2)R) and investigated rV(2)R
      promoter activity in the LLC-PK(1) cell line transfected to express rat V(1a)R
      (rV(1a)R) dominantly (LLC-PK(1)/rV(1a)R). AVP induced a transient increase,
      followed by a sustained decrease, of rV(2)R promoter activity in these cells.
      This AVP-induced decrease of rV(2)R promoter activity was inhibited by V(1a)R,
      but not V(2)R, antagonist. PMA mimicked this decrease of rV(2)R promoter
      activity. On the contrary, 8-(4-chlorophenylthio)-cAMP increased rV(2)R promoter
      activity. These PMA- and 8-(4-chlorophenylthio)-cAMP-induced effects were not
      observed on the deletion segment of the 5'-flanking region lacking CAAT and SP1
      sites. In conclusion, 1) expression of the V(2)R is downregulated via the V(1a)R
      pathway in LLC-PK(1)/rV(1a)R cells, and 2) expression of the V(2)R is
      downregulated by the PMA-induced PKC pathway and upregulated by the cAMP-PKA
      pathway. These opposite effects of PKC and PKA appear to be regulated by the same
      promoter region of CAAT and SP1.

PMID- 17213463
TI  - P2 receptor regulation of [Ca2+]i in cultured mouse mesangial cells.
AB  - Experiments were performed to establish the pharmacological profile of
      purinoceptors and to identify the signal transduction pathways responsible for
      increases in intracellular calcium concentration ([Ca(2+)](i)) for cultured mouse
      mesangial cells. Mouse mesangial cells were loaded with fura 2 and examined using
      fluorescent spectrophotometry. Basal [Ca(2+)](i) averaged 102 +/- 2 nM (n = 346).
      One hundred micromolar concentrations of ATP, ADP, 2',3'-(benzoyl-4-benzoyl)-ATP
      (BzATP), ATP-gamma-S, and UTP in normal Ca(2+) medium evoked peak increases in
      [Ca(2+)](i) of 866 +/- 111, 236 +/- 18, 316 +/- 26, 427 +/- 37, and 808 +/- 73
      nM, respectively. UDP or 2-methylthio-ATP (2MeSATP) failed to elicit significant
      increases in [Ca(2+)](i), whereas identical concentrations of adenosine, AMP, and
      alpha,beta-methylene ATP (alpha,beta-MeATP) had no detectable effect on
      [Ca(2+)](i). Removal of Ca(2+) from the extracellular medium had no significant
      effect on the peak increase in [Ca(2+)](i) induced by ATP, ADP, BzATP, ATP-gamma
      S, or UTP compared with normal Ca(2+); however, Ca(2+)-free conditions did
      accelerate the rate of decline in [Ca(2+)](i) in cells treated with ATP and UTP.
      [Ca(2+)](i) was unaffected by membrane depolarization with 143 mM KCl. Western
      blot analysis for P2 receptors revealed expression of P2X(2), P2X(4), P2X(7),
      P2Y(2), and P2Y(4) receptors. No evidence of P2X(1) and P2X(3) receptor
      expression was detected, whereas RT-PCR analysis reveals mRNA expression for
      P2X(1), P2X(2), P2X(3), P2X(4), P2X(7), P2Y(2), and P2Y(4) receptors. These data
      indicate that receptor-specific P2 receptor activation increases [Ca(2+)](i) by
      stimulating calcium influx from the extracellular medium and through mobilization
      of Ca(2+) from intracellular stores in cultured mouse mesangial cells.

PMID- 17213464
TI  - Renal function measurements from MR renography and a simplified
      multicompartmental model.
AB  - The purpose of this study was to determine the accuracy and sources of error in
      estimating single-kidney glomerular filtration rate (GFR) derived from low-dose
      gadolinium-enhanced T1-weighted MR renography. To analyze imaging data, MR signal
      intensity curves were converted to concentration vs. time curves, and a three
      compartment, six-parameter model of the vascular-nephron system was used to
      analyze measured aortic, cortical, and medullary enhancement curves. Reliability
      of the parameter estimates was evaluated by sensitivity analysis and by Monte
      Carlo analyses of model solutions to which random noise had been added. The
      dominant sensitivity of the medullary enhancement curve to GFR 1-4 min after
      tracer injection was supported by a low coefficient of variation in model-fit GFR
      values (4%) when measured data were subjected to 5% noise. These analyses also
      showed the minimal effects of bolus dispersion in the aorta on parameter
      reliability. Single-kidney GFR from MR renography analyzed by the three
      compartment model (4.0-71.4 ml/min) agreed well with reference measurements from
      (99m)Tc-DTPA clearance and scintigraphy (r = 0.84, P < 0.001). Bland-Altman
      analysis showed an average difference of 11.9 ml/min (95% confidence interval =
      5.8-17.9 ml/min) between model and reference values. We conclude that a nephron
      based multicompartmental model can be used to derive clinically useful estimates
      of single-kidney GFR from low-dose MR renography.

PMID- 17213465
TI  - Vasculotropic, paracrine actions of infused mesenchymal stem cells are important
      to the recovery from acute kidney injury.
AB  - Acute kidney injury (AKI) is a major clinical problem in which a critical
      vascular, pathophysiological component is recognized. We demonstrated previously
      that mesenchymal stem cells (MSC), unlike fibroblasts, are significantly
      renoprotective after ischemia-reperfusion injury and concluded that this
      renoprotection is mediated primarily by paracrine mechanisms. In this study, we
      investigated whether MSC possess vasculoprotective activity that may contribute,
      at least in part, to an improved outcome after ischemia-reperfusion AKI. MSC
      conditioned medium contains VEGF, HGF, and IGF-1 and augments aortic endothelial
      cell (EC) growth and survival, a response not observed with fibroblast
      conditioned medium. MSC and EC share vasculotropic gene expression profiles, as
      both form capillary tubes in vitro on Matrigel alone or in cooperation without
      fusion. MSC undergo differentiation into an endothelial-like cell phenotype in
      culture and develop into vascular structures in vivo. Infused MSC were readily
      detected in the kidney early after reflow but were only rarely engrafted at 1 wk
      post-AKI. MSC attached in the renal microvascular circulation significantly
      decreased apoptosis of adjacent cells. Infusion of MSC immediately after reflow
      in severe ischemia-reperfusion AKI did not improve renal blood flow, renovascular
      resistance, or outer cortical blood flow. These data demonstrate that the unique
      vasculotropic, paracrine actions elicited by MSC play a significant
      renoprotective role after AKI, further demonstrating that cell therapy has
      promise as a novel intervention in AKI.

PMID- 17213466
TI  - Attenuated vasoconstrictor responses to endothelin in afferent arterioles during
      a high-salt diet.
AB  - Endothelin-1 (ET-1) is increased in rats on a high-salt (HS) diet and
      participates in salt-dependent hypertension. Afferent arterioles (AA) are
      important for long-term blood pressure control, and therefore we hypothesized
      that a HS diet would alter their responsiveness to ET-1. Sprague-Dawley rats were
      fed either a normal-salt (NS; 0.66% NaCl) or HS (8%) diet for 1 wk. Diameters of
      AA were determined in response to increasing concentrations of big ET-1, ET-1,
      sarafotoxin 6c (S6c), or norepinephrine (NE), using the blood-perfused
      juxtamedullary nephron technique. ET-1 responses were also determined during
      blockade of endothelin type A (ET(A)) or type B (ET(B)) receptors with 10 nM ABT
      627 or 30 nM A-192621, respectively. Expression of ET(A) and ET(B) receptors was
      determined in renal microvessels. Responses of AA to big ET-1, ET-1, and S6c were
      significantly attenuated during a HS diet (e.g., response to 10(-10) M ET-1 in NS
      vs. HS rats: -52.5 +/- 10.2 vs. +5.6 +/- 11.3% of control diameter; P < 0.05),
      with no change in the responses to NE. ET(B), but not ET(A) receptor blockade
      abolished the different response to ET-1 between the NS and HS groups. ET(B)
      receptor expression in renal microvessels was increased in response to HS (17.7
      +/- 2.4 vs. 6.6 +/- 3.0% of beta-actin, P = 0.02), whereas ET(A) receptor
      expression was unchanged. These results suggest that the reduced vasoconstrictor
      response of AA to endothelin peptides during a HS diet is mediated by increased
      vasodilatory function of endothelial ET(B) receptors. By preserving renal blood
      flow, this may be an important mechanism to restore sodium balance during a HS
      diet.

PMID- 17213467
TI  - The role played by endocytosis in albumin-induced secretion of TGF-beta1 by
      proximal tubular epithelial cells.
AB  - Proteinuria predicts the decline of renal function in chronic kidney disease.
      Reducing albuminuria has been shown to be associated with a reduction in this
      rate of decline. Proximal tubular epithelial cells (PTECs), when exposed to
      albumin produce matrix proteins, proinflammatory and profibrotic cytokines like
      TGF-beta(1). Some of these effects are dependent on endocytosis of albumin by
      PTECs. However, conditions like diabetic nephropathy, believed to be associated
      with reduced albumin endocytosis, are associated with interstitial fibrosis.
      Moreover, megalin, the putative albumin binding receptor in PTECs, has potential
      signaling motifs in its cytoplasmic domain, suggesting its ability to signal in
      response to ligand binding from the apical surface of PTECs. Hence, we looked to
      see whether albumin-induced secretion of TGF-beta(1) by PTECs is dependent on
      albumin endocytosis or whether it could occur in the absence of albumin
      endocytosis. We studied the production of TGF-beta(1) in two accepted models of
      PTECs, opossum kidney cells and human kidney cell clone-8 cells, with widely
      varying degrees of endocytosis. We then studied the effect of inhibiting albumin
      endocytosis with various inhibitors on albumin-induced TGF-beta(1) secretion. Our
      results indicate that albumin-induced TGF-beta(1) secretion by PTECs does not
      require albumin endocytosis and therefore the mechanism for the induction of some
      profibrotic responses by albumin may differ from those required for some of the
      inflammatory responses. Moreover, we found that albumin-induced TGF-beta(1)
      secretion by PTECs is not dependent on its interaction with megalin.

PMID- 17213468
TI  - Rhythm of the beta-cell oscillator is not governed by a single regulator:
      multiple systems contribute to oscillatory behavior.
AB  - Pulsatile insulin output, paralleled by oscillations in intracellular Ca(2+),
      reflect oscillating metabolism within beta-cells in response to secretory fuels.
      Here we question whether oscillatory periodicity is conserved or varied from
      stimulation to stimulation, whether glycolysis is essential for the manifestation
      of an oscillatory response, and if an environment of nutrient oversupply affects
      oscillatory regularity. We have determined that a beta-cell oscillatory Ca(2+)
      pattern is independent of the type of applied secretory fuel (glucose, methyl
      pyruvate, or alpha-ketoisocaproate). In addition, single cells respond with the
      same pattern when repeatedly stimulated, regardless of the type of stimulatory
      fuel. Presence of substimulatory glucose is not necessary to obtain an
      oscillatory responses to methyl-pyruvate or alpha-ketoisocaproate. Glucose-6
      phosphate, as a measure of glycolytic flux, is not detectable under these
      conditions. These data suggest that multiple systems, rather than a single enzyme
      component, can contribute to the beta-cell oscillatory behavior. Prolonged
      exposure to high levels of palmitate impaired oscillatory regularity in the
      individual beta-cells. This supports the hypothesis that a high-fat environment
      might contribute to loss of regular oscillatory pattern in diabetic subjects,
      acting, at least in part, at the level of the single beta-cell.

PMID- 17213469
TI  - Sucrose feeding during pregnancy and lactation elicits distinct metabolic
      response in offspring of an inbred genetic model of metabolic syndrome.
AB  - The importance of early environment, including maternal diet during pregnancy, is
      suspected to play a major role in pathogenesis of metabolic syndrome and related
      conditions. One of the proposed mechanisms is a mismatch between the prenatal and
      postnatal environments, leading to misprogramming of the metabolic and signaling
      pathways of the developing fetus. We assessed whether the exposure to high
      sucrose diet (HSD) alleviates the detrimental effects of sucrose feeding in later
      life (predictive adaptive hypothesis) in a highly inbred model of metabolic
      syndrome, the PD/Cub rat. Rat dams were continuously fed either standard or HSD
      (70% calories as sucrose) starting 1 wk before breeding, throughout pregnancy, at
      birth, and until weaning of the offspring. After weaning, all male offspring were
      fed HSD until the age of 20 wk, when detailed metabolic and morphometric profiles
      were ascertained. The early life exposure to a sucrose-rich diet resulted in
      distinct responses to longtime postnatal HSD feeding. Offspring of the sucrose
      fed mothers displayed higher adiposity and substantial increases in triglyceride
      liver content together with unfavorable distribution of cholesterol into
      lipoprotein subfractions. On the other hand, their adiponectin concentrations
      were significantly higher, and insulin sensitivity of skeletal muscle was
      enhanced compared with the offspring of standard diet-fed mothers. Triglycerides,
      free fatty acids, overall glucose tolerance, and the insulin sensitivity of
      adipose tissue were comparable in both groups. In the genetically identical
      animals, maternal HSD feeding elicited a variety of subtle effects but did not
      lead to predictive adaptive protection from most HSD-induced metabolic
      derangements.

PMID- 17213470
TI  - Glucose and insulin improve cardiac efficiency and postischemic functional
      recovery in perfused hearts from type 2 diabetic (db/db) mice.
AB  - Hearts from type 2 diabetic (db/db) mice demonstrate altered substrate
      utilization with high rates of fatty acid oxidation, decreased functional
      recovery following ischemia, and reduced cardiac efficiency. Although db/db mice
      show overall insulin resistance in vivo, we recently reported that insulin
      induces a marked shift toward glucose oxidation in isolated perfused db/db
      hearts. We hypothesize that such a shift in metabolism should improve cardiac
      efficiency and consequently increase functional recovery following low-flow
      ischemia. Hearts from db/db and nondiabetic (db/+) mice were perfused with 0.7 mM
      palmitate plus either 5 mM glucose (G), 5 mM glucose and 300 microU/ml insulin
      (GI), or 33 mM glucose and 900 microU/ml insulin (HGHI). Substrate oxidation and
      postischemic recovery were only moderately affected by GI and HGHI in db/+
      hearts. In contrast, GI and particularly HGHI markedly increased glucose
      oxidation and improved postischemic functional recovery in db/db hearts. Cardiac
      efficiency was significantly improved in db/db, but not in db/+ hearts, in the
      presence of HGHI. In conclusion, insulin and glucose normalize cardiac
      metabolism, restore efficiency, and improve postischemic recovery in type 2
      diabetic mouse hearts. These findings may in part explain the beneficial effect
      of glucose-insulin-potassium therapy in diabetic patients with cardiac
      complications.

PMID- 17213471
TI  - Differential effects of somatostatin on circulating tissue factor procoagulant
      activity and protein.
AB  - The tissue factor (TF) pathway is the primary mechanism for initiation of blood
      coagulation. Circulating blood contains TF, which originates mainly from
      monocytes and is thrombogenic. The presence of somatostatin (SMS) receptors on
      monocytes suggests the possibility that SMS may regulate TF synthesis and/or
      release. Circulating TF procoagulant activity (TF-PCA), factor VIIa activity
      (FVIIa; clotting assays), TF antigen (TF-Ag; ELISA), prothrombin fragment 1.2
      (F1.2), thrombin-antithrombin complexes (ELISAs), CD40 ligand expression on
      platelets, and monocyte-platelet aggregates (flow cytometry) were determined in
      blood from normal volunteers undergoing 24 h of basal glucose/basal insulin
      (BG/BI) clamps and high-glucose/high-insulin (HG/HI) clamps with and without SMS.
      Infusions of SMS under basal conditions (BG/BI) raised TF-PCA 1.8-fold (P <
      0.03), TF-Ag 2.3-fold (P < 0.001), and TF expression on monocytes by 36% (P <
      0.001) and decreased plasma levels of FVIIa by 30% (P < 0.001). Infusion of SMS
      reduced the 8.6-fold HG/HI-induced increase in TF-Ag by 26% and the 8.6-fold
      increase in TF-PCA by 100%. SMS also prevented the 60% increase in TF expression
      on monocytes, the 2.2-fold increase in F1.2, the 40% increase in CD40L expression
      on platelets, and the 17% increase in monocyte-platelet aggregates seen during
      HG/HI. We conclude that SMS completely prevented HG/HI-induced TF activation in
      normal volunteers and may be of use to reduce the procoagulant state and acute
      vascular events in hyperinsulinemic insulin-resistant patients with type 2
      diabetes.

PMID- 17213472
TI  - Transgenerational inheritance of the insulin-resistant phenotype in embryo
      transferred intrauterine growth-restricted adult female rat offspring.
AB  - To determine mechanisms underlying the transgenerational presence of metabolic
      perturbations in the intrauterine growth-restricted second-generation adult
      females (F2 IUGR) despite normalizing the in utero metabolic environment, we
      examined in vivo glucose kinetics and in vitro skeletal muscle postinsulin
      receptor signaling after embryo transfer of first generation (F1 IUGR) to control
      maternal environment. Female F2 rats, procreated by F1 pre- and postnatally
      nutrient- and growth-restricted (IUGR) mothers but embryo transferred to gestate
      in control mothers, were compared with similarly gestating age- and sex-matched
      control (CON) F2 progeny. Although there were no differences in birth weight or
      postnatal growth patterns, the F2 IUGR had increased hepatic weight, fasting
      hyperglycemia, hyperinsulinemia, and unsuppressed hepatic glucose production,
      with no change in glucose futile cycling or clearance, compared with F2 CON.
      These hormonal and metabolic aberrations were associated with increased skeletal
      muscle total GLUT4 and pAkt concentrations but decreased plasma membrane
      associated GLUT4, total pPKCzeta, and PKCzeta enzyme activity, with no change in
      total SHP2 and PTP1B concentrations in IUGR F2 compared with F2 CON. We conclude
      that transgenerational presence of aberrant glucose/insulin metabolism and
      skeletal muscle insulin signaling of the adult F2 IUGR female offspring is
      independent of the immediate intrauterine environment, supporting nutritionally
      induced heritable mechanisms contributing to the epidemic of type 2 diabetes
      mellitus.

PMID- 17213473
TI  - Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at
      the onset of mild tetanic skeletal muscle contraction.
AB  - The Ca(2+)/calmodulin (CaM) competitive inhibitor KN-93 has previously been used
      to evaluate 5'-AMP-activated protein kinase (AMPK)-independent Ca(2+)-signaling
      to contraction-stimulated glucose uptake in muscle during intense electrical
      stimulation ex vivo. With the use of low-intensity tetanic contraction of mouse
      soleus and extensor digitorum longus (EDL) muscles ex vivo, this study
      demonstrates that KN-93 can potently inhibit AMPK phosphorylation and activity
      after 2 min but not 10 min of contraction while strongly inhibiting contraction
      stimulated 2-deoxyglucose uptake at both the 2- and 10-min time points. These
      data suggest inhibition of Ca(2+)/CaM-dependent signaling events upstream of
      AMPK, the most likely candidate being the novel AMPK kinase CaM-dependent protein
      kinase kinase (CaMKK). CaMKK protein expression was detected in mouse skeletal
      muscle. Similar to KN-93, the CaMKK inhibitor STO-609 strongly reduced AMPK
      phosphorylation and activity at 2 min and less potently at 10 min. Pretreatment
      with STO-609 inhibited contraction-stimulated glucose uptake at 2 min in soleus,
      but not EDL, and in both muscles after 10 min. Neither KN-93 nor STO-609
      inhibited 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside-stimulated
      glucose uptake, AMPK phosphorylation, or recombinant LKB1 activity, suggestive of
      an LKB1-independent effect. Finally, neither KN-93 nor STO-609 had effects on the
      reductions in glucose uptake seen in mice overexpressing a kinase-dead AMPK
      construct, indicating that the effects of KN-93 and STO-609 on glucose uptake
      require inhibition of AMPK activity. We propose that CaMKKs act in mouse skeletal
      muscle regulating AMPK phosphorylation and glucose uptake at the onset of mild
      tetanic contraction and that an intensity- and/or time-dependent switch occurs in
      the relative importance of AMPKKs during contraction.

PMID- 17213474
TI  - Hepatic autoregulation: response of glucose production and gluconeogenesis to
      increased glycogenolysis.
AB  - The effect of increased glycogenolysis, simulated by galactose's conversion to
      glucose, on the contribution of gluconeogenesis (GNG) to hepatic glucose
      production (GP) was determined. The conversion of galactose to glucose is by the
      same pathway as glycogen's conversion to glucose, i.e., glucose 1-phosphate -->
      glucose 6-phosphate --> glucose. Healthy men (n = 7) were fasted for 44 h. At 40
      h, hepatic glycogen stores were depleted. GNG then contributed approximately 90%
      to a GP of approximately 8 micromol.kg(-1).min(-1). Galactose, 9 g/h, was infused
      over the next 4 h. The contribution of GNG to GP declined from approximately 90%
      to 65%, i.e., by approximately 2 micromol.kg(-1).min(-1). The rate of galactose
      conversion to blood glucose, measured by labeling the infused galactose with [1
      (2)H]galactose (n = 4), was also approximately 2 micromol.kg(-1).min(-1). The
      41st h GP rose by approximately 1.5 micromol.kg(-1).min(-1) and then returned to
      approximately 9 micromol.kg(-1).min(-1), while plasma glucose concentration
      increased from approximately 4.5 to 5.3 mM, accompanied by a rise in plasma
      insulin concentration. Over 50% of the galactose infused was accounted for in
      blood glucose and hepatic glycogen formation. Thus an increase in the rate of GP
      via the glycogenolytic pathway resulted in a concomitant decrease in the rate of
      GP via GNG. While the compensatory response to the galactose administration was
      not complete, since GP increased, hepatic autoregulation is operative in healthy
      humans during prolonged fasting.

PMID- 17213475
TI  - Glucose transporter isoform-3 mutations cause early pregnancy loss and fetal
      growth restriction.
AB  - Glucose transporter isoform-3 (GLUT3) is the trophoblastic facilitative glucose
      transporter. To investigate the role of this isoform in embryonic development, we
      created a novel GLUT3-null mouse and observed arrested early embryonic
      development and loss at neurulation stage when both alleles were mutated. This
      loss occurred despite the presence of other related isoforms, particularly GLUT1.
      In contrast, when a single allele was mutated, despite increased embryonic cell
      apoptosis, adaptive changes in the subcellular localization of GLUT3 and GLUT1 in
      the preimplantation embryo led to postimplantation survival. This survival was
      compromised by decreased GLUT3-mediated transplacental glucose transport, causing
      late-gestation fetal growth restriction. This yielded young male and female
      adults demonstrating catch-up growth, with normal basal glucose, insulin, insulin
      like growth factor-I and IGF-binding protein-3 concentrations, fat and lean mass,
      and glucose and insulin tolerance. We conclude that GLUT3 mutations cause a gene
      dose-dependent early pregnancy loss or late-gestation fetal growth restriction
      despite the presence of embryonic and placental GLUT1 and a compensatory increase
      in system A amino acid placental transport. This critical life-sustaining
      functional role for GLUT3 in embryonic development provides the basis for
      investigating the existence of human GLUT3 mutations with similar consequences
      during early pregnancy.

PMID- 17213476
TI  - Insulin-sensitizing effects of thiazolidinediones are not linked to adiponectin
      receptor expression in human fat or muscle.
AB  - Circulating adiponectin levels are increased by the thiazolidinedione (TZD) class
      of PPARgamma agonists in concert with their insulin-sensitizing effects. Two
      receptors for adiponectin (AdipoR1 and AdipoR2) are widely expressed in many
      tissues, but their physiological significance to human insulin resistance remains
      to be fully elucidated. We examined the expression patterns of AdipoR1 and
      AdipoR2 in fat and skeletal muscle of human subjects, their relationship to
      insulin action, and whether they are regulated by TZDs. Expression patterns of
      both AdipoRs were similar in subcutaneous and omental fat depots, with higher
      expression in adipocytes than in stromal cells and macrophages. To determine the
      effects of TZDs on AdipoR expression, subcutaneous fat and quadriceps muscle were
      biopsied in 14 insulin-resistant subjects with type 2 diabetes mellitus after 45
      mg pioglitazone or placebo for 21 days. This duration of pioglitazone improved
      insulin's suppression of glucose production by 41% and enhanced stimulation of
      glucose uptake by 27% in concert with increased gene expression and plasma levels
      of adiponectin. Pioglitazone did not affect AdipoR expression in muscle, whole
      fat, or cellular adipose fractions, and receptor expression did not correlate
      with baseline or TZD-enhanced insulin action. In summary, both adiponectin
      receptors are expressed in cellular fractions of human fat, particularly
      adipocytes. TZD administration for sufficient duration to improve insulin action
      and increase adiponectin levels did not affect expression of AdipoR1 or AdipoR2.
      Although TZDs probably exert many of their effects via adiponectin, changes in
      these receptors do not appear to be necessary for their insulin-sensitizing
      effects.

PMID- 17213477
TI  - Angiotensin II increases adipose angiotensinogen expression.
AB  - In addition to the well-defined contribution of the liver, adipose tissue has
      been recognized as an important source of angiotensinogen (AGT). The purpose of
      this study was to define the angiotensin II (ANG II) receptors involved in
      regulation of adipose AGT and the relationship of this control to systemic AGT
      and/or angiotensin peptide concentrations. In LDL receptor-deficient (LDLR(-/-))
      male mice, adipose mRNA abundance of AGT was 68% of that in liver, and adipose
      mRNA abundance of the angiotensin type 1a (AT(1a)) receptor (AT(1a)R) was 38% of
      that in liver, whereas mRNA abundance of the angiotensin type 2 (AT(2)) receptor
      (AT(2)R) was 57% greater in adipose tissue than in liver. AGT and angiotensin
      peptide concentrations were decreased in plasma of AT(1a)R-deficient (AT(1a)R(-/
      )) mice and were paralleled by reductions in AGT expression in liver. In
      contrast, adipose AGT mRNA abundance was unaltered in AT(1a)R(-/-) mice. AT(2)R(
      /-) mice exhibited elevated plasma angiotensin peptide concentrations and marked
      elevations in adipose AGT and AT(1a)R mRNA abundance. Increases in adipose AGT
      mRNA abundance in AT(2)R(-/-) mice were abolished by losartan. In contrast, liver
      AGT and AT(1a)R mRNA abundance were unaltered in AT(2)R(-/-) mice. Infusion of
      ANG II for 28 days into LDLR(-/-) mice markedly increased adipose AGT and AT(1a)R
      mRNA but did not alter liver AGT and AT(1a)R mRNA. These results demonstrate that
      differential mRNA abundance of AT(1a)/AT(2) receptors in adipose tissue vs. liver
      contributes to tissue-specific ANG II-mediated regulation of AGT. Chronic
      infusion of ANG II robustly stimulated AT(1a)R and AGT mRNA abundance in adipose
      tissue, suggesting that adipose tissue serves as a primary contributor to the
      activated systemic renin-angiotensin system.

PMID- 17213478
TI  - Chronic fetal hypoglycemia inhibits the later steps of stimulus-secretion
      coupling in pancreatic beta-cells.
AB  - We measured the impact of chronic late gestation hypoglycemia on pancreatic islet
      structure and function to determine the cause of decreased insulin secretion in
      this sheep model of fetal nutrient deprivation. Late gestation hypoglycemia did
      not decrease pancreas weight, insulin content, beta-cell area, beta-cell mass, or
      islet size. The pancreatic islet isolation procedure selected a group of islets
      that were larger and had an increased proportion of beta-cells compared with
      islets measured in pancreatic sections, but there were no morphologic differences
      between islets isolated from control and hypoglycemic fetuses. The rates of
      glucose-stimulated pancreatic islet glucose utilization (126.2 +/- 25.3 pmol
      glucose.islet(-1).h(-1), hypoglycemic, vs. 93.5 +/- 5.5 pmol glucose.islet(-1).h(
      1), control, P = 0.47) and oxidation (10.5 +/- 1.7 pmol glucose.islet(-1).h(-1),
      hypoglycemic, vs. 10.6 +/- 1.6 pmol glucose.islet(-1).h(-1), control) were not
      different in hypoglycemic fetuses compared with control fetuses. Chronic late
      gestation hypoglycemia decreased insulin secretion in isolated pancreatic islets
      by almost 70% in response to direct nonnutrient membrane depolarization and in
      response to increased extracellular calcium entry. beta-Cell ultrastructure was
      abnormal with markedly distended rough endoplasmic reticulum in three of the
      seven hypoglycemic fetuses studied, but in vitro analysis of hypoglycemic control
      islets showed no evidence that these changes represented endoplasmic reticulum
      stress, as measured by transcription of glucose regulatory protein-78 and
      processing of X-box binding protein-1. In conclusion, these studies show that
      chronic hypoglycemia in late gestation decreases insulin secretion by inhibiting
      the later steps of stimulus-secretion coupling after glucose metabolism, membrane
      depolarization, and calcium entry.

PMID- 17213479
TI  - Religious beliefs in schizophrenia: their relevance for adherence to treatment.
AB  - The study examined how religious beliefs and practices impact upon medication and
      illness representations in chronic schizophrenia. One hundred three stabilized
      patients were included in Geneva's outpatient public psychiatric facility in
      Switzerland. Interviews were conducted to investigate spiritual and religious
      beliefs and religious practices and religious coping. Medication adherence was
      assessed through questions to patients and to their psychiatrists and by a
      systematic blood drug monitoring. Thirty-two percent of patients were partially
      or totally nonadherent to oral medication. Fifty-eight percent of patients were
      Christians, 2% Jewish, 3% Muslim, 4% Buddhist, 14% belonged to various minority
      or syncretic religious movements, and 19% had no religious affiliation. Two
      thirds of the total sample considered spirituality as very important or even
      essential in everyday life. Fifty-seven percent of patients had a representation
      of their illness directly influenced by their spiritual beliefs (positively in
      31% and negatively in 26%). Religious representations of illness were prominent
      in nonadherent patients. Thirty-one percent of nonadherent patients and 27% of
      partially adherent patients underlined an incompatibility or contradiction
      between their religion and taking medication, versus 8% of adherent patients.
      Religion and spirituality contribute to shaping representations of disease and
      attitudes toward medical treatment in patients with schizophrenia. This dimension
      should be on the agenda of psychiatrists working with patients with
      schizophrenia.

PMID- 17213480
TI  - Cigarette smoke-induced proinflammatory alterations in the endothelial phenotype:
      role of NAD(P)H oxidase activation.
AB  - Although the cardiovascular morbidity and mortality induced by cigarette smoking
      exceed those attributable to lung cancer, the molecular basis of smoking-induced
      vascular injury remains unclear. To test the link between cigarette smoke,
      oxidative stress, and vascular inflammation, rats were exposed to the smoke of
      five cigarettes per day (for 1 wk). Also, isolated arteries were exposed to
      cigarette smoke extract (CSE; 0 to 40 microg/ml, for 6 h) in organoid culture. We
      found that smoking impaired acetylcholine-induced relaxations of carotid
      arteries, which could be improved by the NAD(P)H oxidase inhibitor apocynin.
      Lucigenin chemiluminescence measurements showed that both smoking and in vitro
      CSE exposure significantly increased vascular O(2)(*-) production.
      Dihydroethidine staining showed that increased O(2)(*-) generation was present
      both in endothelial and smooth muscle cells. CSE also increased vascular H(2)O(2)
      production (dichlorofluorescein fluorescence). Vascular mRNA expression of the
      proinflammatory cytokines IL-1beta, IL-6, and TNF-alpha and that of inducible
      nitric oxide synthase was significantly increased by both smoking and CSE
      exposure, which could be prevented by inhibition of NAD(P)H oxidase
      (diphenyleneiodonium and apocynin) or scavenging of H(2)O(2). In cultured
      endothelial cells, CSE elicited NF-kappaB activation and increased monocyte
      adhesiveness, which were prevented by apocynin and catalase. Thus we propose that
      water-soluble components of cigarette smoke (which are likely to be present in
      the bloodstream in vivo in smokers) activate the vascular NAD(P)H oxidase.
      NAD(P)H oxidase-derived H(2)O(2) activates NF-kappaB, leading to proinflammatory
      alterations in vascular phenotype, which likely promotes development of
      atherosclerosis, especially if other risk factors are also present.

PMID- 17213481
TI  - 17beta-Estradiol modulates vasoconstriction induced by endothelin-1 following
      trauma-hemorrhage.
AB  - Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether
      17beta-estradiol (E(2)) treatment following trauma-hemorrhage alters these ET-1
      induced vasoconstrictive effects. In addition, the role of the specific estrogen
      receptor (ER) subtypes (ER-alpha and ER-beta) and the endothelium-localized
      downstream mechanisms of actions of E(2) remain unclear. We hypothesized that
      E(2) attenuates increased ET-1-induced vasoconstriction following trauma
      hemorrhage via an ER-beta-mediated pathway. To study this, aortic rings were
      isolated from male Sprague-Dawley rats following trauma-hemorrhage with or
      without E(2) treatment, and alterations in tension were determined in vitro. Dose
      response curves to ET-1 were determined, and the vasoactive properties of E(2),
      propylpyrazole triol (PPT, ER-alpha agonist), and diarylpropionitrile (DPN, ER
      beta agonist) were determined. The results showed that trauma-hemorrhage
      significantly increased ET-1-induced vasoconstriction; however, administration of
      E(2) normalized ET-1-induced vasoconstriction in trauma-hemorrhage vessels to the
      sham-operated control level. The ER-beta agonist DPN counteracted ET-1-induced
      vasoconstriction, whereas the ER-alpha agonist PPT was ineffective. Moreover, the
      vasorelaxing effects of E(2) were not observed in endothelium-denuded aortic
      rings or by pretreatment of the rings with a nitric oxide (NO) synthase
      inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the
      action of E(2). Thus, E(2) administration attenuates ET-1-induced
      vasoconstriction following trauma-hemorrhage via an ER-beta-mediated pathway that
      is dependent on endothelium-derived NO synthesis.

PMID- 17213482
TI  - Angiotensin-(1-7) prevents diabetes-induced cardiovascular dysfunction.
AB  - The aim of this study was to test the hypothesis that treatment with angiotensin
      (1-7) [ANG-(1-7)] or ANG-(1-7) nonpeptide analog AVE-0991 can produce protection
      against diabetes-induced cardiovascular dysfunction. We examined the influence of
      chronic treatment (4 wk) with ANG-(1-7) (576 microg.kg(-1).day(-1) ip) or AVE
      0991 (576 microg.kg(-1).day(-1) ip) on proteinuria, vascular responsiveness of
      isolated carotid and renal artery ring segments and mesenteric bed to vasoactive
      agonists, and cardiac recovery from ischemia-reperfusion in streptozotocin
      treated rats (diabetes). Animals were killed 4 wk after induction of diabetes
      and/or treatment with ANG-(1-7) or AVE-0991. There was a significant increase in
      urine protein (231 +/- 2 mg/24 h) in diabetic animals compared with controls (88
      +/- 6 mg/24 h). Treatment of diabetic animals with ANG-(1-7) or AVE-0991 resulted
      in a significant reduction in urine protein compared with vehicle-treated
      diabetic animals (183 +/- 16 and 149 +/- 15 mg/24 h, respectively). Treatment
      with ANG-(1-7) or AVE-0991 also prevented the diabetes-induced abnormal vascular
      responsiveness to norepinephrine, endothelin-1, angiotensin II, carbachol, and
      histamine in the perfused mesenteric bed and isolated carotid and renal arteries.
      In isolated perfused hearts, recovery of left ventricular function from 40 min of
      global ischemia was significantly better in ANG-(1-7)- or AVE-0991-treated
      animals. These results suggest that activation of ANG-(1-7)-mediated signal
      transduction could be an important therapeutic strategy to reduce cardiovascular
      events in diabetic patients.

PMID- 17213484
TI  - Cell-based multiwell assays for the detection of substrate accumulation and
      oxidation.
AB  - We describe multiwell assays for detecting the accumulation as well as the
      subsequent oxidation of (14)C-labeled substrates in cultured cells. Accumulation
      is monitored in real time by an established scintillation proximity assay in
      which the scintillator is embedded in the plate base primarily detecting cell
      associated radiolabel. The substrate oxidation assay is a novel variant of
      previously described experimental approaches aimed at trapping (14)CO(2) produced
      by isolated enzymes, organelles, or intact cells. This method uses a standard 96
      well tissue culture plate and, on top, an inverted filter plate immersed with
      NaOH that are clamped into a sandwich sealed with a silicon gasket to obtain gas
      tight compartments. (14)CO(2) is captured in the filter and quantified by
      conventional scintillation. We demonstrate both the accumulation and subsequent
      oxidation of (14)C-labeled substrates in cultured human myotubes, adipocytes, and
      hepatocytes. Both methods are adaptable for compound screening; at the same time,
      these protocols provide easy-to-use and time- saving methods for in vitro studies
      of cellular fuel handling.

PMID- 17213485
TI  - Service-oriented architecture in medical software: promises and perils.

PMID- 17213487
TI  - A roadmap for national action on clinical decision support.
AB  - This document comprises an AMIA Board of Directors approved White Paper that
      presents a roadmap for national action on clinical decision support. It is
      published in JAMIA for archival and dissemination purposes. The full text of this
      material has been previously published on the AMIA Web site
      (www.amia.org/inside/initiatives/cds). AMIA is the copyright holder.

PMID- 17213488
TI  - Re: "A security analysis of the Verichip implantable RFID device" JAMIA PrePrint:
      accepted article. Published August 23, 2006 as doi:10.1197/jamia.M2143.

PMID- 17213489
TI  - Proposal for fulfilling strategic objectives of the U.S. Roadmap for national
      action on clinical decision support through a service-oriented architecture
      leveraging HL7 services.
AB  - Despite their demonstrated effectiveness, clinical decision support (CDS) systems
      are not widely used within the U.S. The Roadmap for National Action on Clinical
      Decision Support, published in June 2006 by the American Medical Informatics
      Association, identifies six strategic objectives for achieving widespread
      adoption of effective CDS capabilities. In this manuscript, we propose a Service
      Oriented Architecture (SOA) for CDS that facilitates achievement of these six
      objectives. Within the proposed framework, CDS capabilities are implemented
      through the orchestration of independent software services whose interfaces are
      being standardized by Health Level 7 and the Object Management Group through
      their joint Healthcare Services Specification Project (HSSP). Core services
      within this framework include the HSSP Decision Support Service, the HSSP Common
      Terminology Service, and the HSSP Retrieve, Locate, and Update Service. Our
      experiences, and those of others, indicate that the proposed SOA approach to CDS
      could enable the widespread adoption of effective CDS within the U.S. health care
      system.

PMID- 17213490
TI  - Response to Corrao et al.: Improving efficacy of PubMed clinical queries for
      retrieving scientifically strong studies on treatment.

PMID- 17213491
TI  - Informatics systems to promote improved care for chronic illness: a literature
      review.
AB  - OBJECTIVE: To understand information systems components important in supporting
      team-based care of chronic illness through a literature search. DESIGN:
      Systematic search of literature from 1996-2005 for evaluations of information
      systems used in the care of chronic illness. MEASUREMENTS: The relationship of
      design, quality, information systems components, setting, and other factors with
      process, quality outcomes, and health care costs was evaluated. RESULTS: In all,
      109 articles were reviewed involving 112 information system descriptions. Chronic
      diseases targeted included diabetes (42.9% of reviewed articles), heart disease
      (36.6%), and mental illness (23.2%), among others. System users were primarily
      physicians, nurses, and patients. Sixty-seven percent of reviewed experiments had
      positive outcomes; 94% of uncontrolled, observational studies claimed positive
      results. Components closely correlated with positive experimental results were
      connection to an electronic medical record, computerized prompts, population
      management (including reports and feedback), specialized decision support,
      electronic scheduling, and personal health records. Barriers identified included
      costs, data privacy and security concerns, and failure to consider workflow.
      CONCLUSION The majority of published studies revealed a positive impact of
      specific health information technology components on chronic illness care.
      Implications for future research and system designs are discussed.

PMID- 17213493
TI  - The prevalence and inaccessibility of Internet references in the biomedical
      literature at the time of publication.
AB  - OBJECTIVES: To determine the prevalence and inaccessibility of Internet
      references in the bibliography of biomedical publications when first released in
      PubMed. METHODS: During a one-month observational study period (Feb 21 to Mar 21,
      2006) the Internet citations from a 20% random sample of all forthcoming
      publications released in PubMed during the previous day were identified. Attempts
      to access the referenced Internet citations were completed within one day and
      inaccessible Internet citations were recorded. RESULTS: The study included 4,699
      publications from 844 different journals. Among the 141,845 references there were
      840 (0.6%) Internet citations. One or more Internet references were cited in 403
      (8.6%) articles. From the 840 Internet references, 11.9% were already
      inaccessible within two days after an article's release to the public.
      CONCLUSION: The prevalence of Internet citations in journals included in PubMed
      is small (<1%); however, the inaccessibility rate at the time of publication is
      considered substantial. Authors, editors, and publishers need to take
      responsibility for providing accurate and accessible Internet references.

PMID- 17213492
TI  - Linking surveillance to action: incorporation of real-time regional data into a
      medical decision rule.
AB  - OBJECTIVE: Broadly, to create a bidirectional communication link between public
      health surveillance and clinical practice. Specifically, to measure the impact of
      integrating public health surveillance data into an existing clinical prediction
      rule. We incorporate data about recent local trends in meningitis epidemiology
      into a prediction model differentiating aseptic from bacterial meningitis. DESIGN
      AND MEASUREMENTS: Retrospective analysis of a cohort of all 696 children with
      meningitis admitted to a large urban pediatric hospital from 1992 to 2000. We
      modified a published bacterial meningitis score by adding a new epidemiological
      context adjustor variable. We examined 540 possible rules for this adjustor,
      varying both the number of aseptic meningitis cases that needed to be seen, and
      the recent time window in which they were seen. We performed sensitivity analyses
      with each of 540 possibilities in order to identify the optimal rule--namely, the
      one that included the most cases of aseptic meningitis without missing additional
      cases of bacterial meningitis, as compared with the published prediction model.
      We used bootstrap methods to validate this new score. RESULTS: The optimal rule
      was found to be: "at least four cases of aseptic meningitis in the previous 10
      days." The epidemiological context adjustor based on surveillance of recent cases
      of meningitis allowed the correct identification of an additional 47 cases (7%)
      of aseptic meningitis without missing any additional cases of bacterial
      meningitis. The epidemiological context adjustor was validated, showing
      significance in 84% of 1,000 bootstrap samples. CONCLUSION: Epidemiological
      contextual information can improve the performance of a clinical prediction rule.
      We provide a methodological framework for leveraging regional surveillance data
      to improve medical decision-making.

PMID- 17213494
TI  - Evaluation of an intelligent tutoring system in pathology: effects of external
      representation on performance gains, metacognition, and acceptance.
AB  - OBJECTIVE: Determine effects of computer-based tutoring on diagnostic performance
      gains, meta-cognition, and acceptance using two different problem
      representations. Describe impact of tutoring on spectrum of diagnostic skills
      required for task performance. Identify key features of student-tutor interaction
      contributing to learning gains. DESIGN: Prospective, between-subjects study,
      controlled for participant level of training. Resident physicians in two academic
      pathology programs spent four hours using one of two interfaces which differed
      mainly in external problem representation. The case-focused representation
      provided an open-learning environment in which students were free to explore
      evidence-hypothesis relationships within a case, but could not visualize the
      entire diagnostic space. The knowledge-focused representation provided an
      interactive representation of the entire diagnostic space, which more tightly
      constrained student actions. MEASUREMENTS: Metrics included results of pretest,
      post-test and retention-test for multiple choice and case diagnosis tests, ratios
      of performance to student reported certainty, results of participant survey,
      learning curves, and interaction behaviors during tutoring. RESULTS: Students had
      highly significant learning gains after one tutoring session. Learning was
      retained at one week. There were no differences between the two interfaces in
      learning gains on post-test or retention test. Only students in the knowledge
      focused interface exhibited significant metacognitive gains from pretest to post
      test and pretest to retention test. Students rated the knowledge-focused
      interface significantly higher than the case-focused interface. CONCLUSIONS:
      Cognitive tutoring is associated with improved diagnostic performance in a
      complex medical domain. The effect is retained at one-week post-training.
      Knowledge-focused external problem representation shows an advantage over case
      focused representation for metacognitive effects and user acceptance.

PMID- 17213495
TI  - Implementation and use of an electronic health record within the Indian Health
      Service.
AB  - OBJECTIVES: There are limited data regarding implementing electronic health
      records (EHR) in underserved settings. We evaluated the implementation of an EHR
      within the Indian Health Service (IHS), a federally funded health system for
      Native Americans. DESIGN: We surveyed 223 primary care clinicians practicing at
      26 IHS health centers that implemented an EHR between 2003 and 2005. METHODS: The
      survey instrument assessed clinician attitudes regarding EHR implementation,
      current utilization of individual EHR functions, and attitudes regarding the use
      of information technology to improve quality of care in underserved settings. We
      fit a multivariable logistic regression model to identify correlates of increased
      utilization of the EHR. RESULTS: The overall response rate was 56%. Of responding
      clinicians, 66% felt that the EHR implementation process was positive. One-third
      (35%) believed that the EHR improved overall quality of care, with many (39%)
      feeling that it decreased the quality of the patient-doctor interaction. One
      third of clinicians (34%) reported consistent use of electronic reminders, and
      self-report that EHRs improve quality was strongly associated with increased
      utilization of the EHR (odds ratio 3.03, 95% confidence interval 1.05-8.8). The
      majority (87%) of clinicians felt that information technology could potentially
      improve quality of care in rural and underserved settings through the use of
      tools such as online information sources, telemedicine programs, and electronic
      health records. CONCLUSIONS: Clinicians support the use of information technology
      to improve quality in underserved settings, but many felt that it was not
      currently fulfilling its potential in the IHS, potentially due to limited use of
      key functions within the EHR.

PMID- 17213496
TI  - Emergency department access to a longitudinal medical record.
AB  - Our goal is to assess how clinical information from previous visits is used in
      the emergency department. We used detailed user audit logs to measure access to
      different data types. We found that clinician-authored notes and laboratory and
      radiology data were used most often (common data types were used up to 5% to 20%
      of the time). Data were accessed less than half the time (up to 20% to 50%) even
      when the user was alerted to the presence of data. Our access rate indicates that
      health information exchange projects should be conservative in estimating how
      often shared data will be used and the wide breadth of data accessed indicates
      that although a clinical summary is likely to be useful, an ideal solution will
      supply a broad variety of data.

PMID- 17213497
TI  - Analysis of a study of the users, uses, and future agenda of the UMLS.
AB  - OBJECTIVES: The UMLS constitutes the largest existing collection of medical
      terms. However, little has been published about the users and uses of the UMLS.
      This study sheds light on these issues. DESIGN: We designed a questionnaire
      consisting of 26 questions and distributed it to the UMLS user mailing list.
      Participants were assured complete confidentiality of their replies. To further
      encourage list members to respond, we promised to provide them with early results
      prior to publication. Sector analysis of the responses, according to employment
      organizations is used to obtain insights into some responses. RESULTS: We
      received 70 responses. The study confirms two intended uses of the UMLS: access
      to source terminologies (75%), and mapping among them (44%). However, most access
      is just to a few sources, led by SNOMED, MeSH, and ICD. Out of 119 reported
      purposes of use, terminology research (37), information retrieval (19), and
      terminology translation (14) lead. Four important observations are that the UMLS
      is widely used as a terminology (77%), even though it was not designed as one;
      many users (73%) want the NLM to mark concepts with multiple parents in an
      indented hierarchy and to derive a terminology from the UMLS (73%). Finally,
      auditing the UMLS is a top budget priority (35%) for users. CONCLUSIONS: The
      study reports many uses of the UMLS in a variety of subjects from terminology
      research to decision support and phenotyping. The study confirms that the UMLS is
      used to access its source terminologies and to map among them. Two primary
      concerns of the existing user base are auditing the UMLS and the design of a UMLS
      based derived terminology.

PMID- 17213499
TI  - Integrating incident reporting into an electronic patient record system.
AB  - Developments in information technology offer new opportunities to design
      electronic patient record systems (EPR) which integrate a broad range of
      functions such as clinical decision support, order entry, or electronic alerts.
      It has been recently suggested that EPR could support new applications for
      disease surveillance and patient safety. We describe the integration of a
      voluntary incident reporting system into an EPR used in operating theatres, to
      allow the reporting of accidents and preventable complications. We assessed
      system's reliability and users' acceptance. During the 4-years observation period
      (2002-2006), 48,983 interventional procedures were performed. Clinicians
      documented 85.1% of procedures on the incident reporting form. Agreement between
      chart review and electronically reported incidents was 80.6%. The integration of
      an incident reporting system into an EPR is reliable and well supported by health
      care professionals.

PMID- 17213498
TI  - Impact on quality of life of a telemedicine system supporting head and neck
      cancer patients: a controlled trial during the postoperative period at home.
AB  - OBJECTIVES: Telemedicine applications carry the potential to enhance the quality
      of life of patients, but studies evaluating telemedicine applications are still
      scarce. The evidence regarding the effectiveness of telemedicine is limited and
      not yet conclusive. This study investigated whether telemedicine could be
      beneficial to the quality of life of cancer patients. DESIGN AND MEASUREMENTS:
      Between 1999 and 2002, we conducted a prospective controlled trial evaluating the
      effects of a telemedicine application on the quality of life of patients with
      cancer involving the head and neck, using quality of life questionnaires that
      covered 22 quality of life parameters. All patients had undergone surgery for
      head and neck cancer at the Erasmus MC, a tertiary university hospital in The
      Netherlands. Patients in the intervention group were given access to an
      electronic health information support system for a period of six weeks, starting
      at discharge from the hospital. RESULTS: In total, we included 145 patients in
      the control group and 39 in the intervention group. At 6 weeks, the end of the
      intervention, the intervention group had significantly improved QoL in 5 of the
      22 studied parameters. Only one of these five quality of life parameters remained
      significantly different at 12 weeks. CONCLUSIONS: This study adds to the sparse
      evidence that telemedicine may be beneficial for the quality of life of cancer
      patients.

PMID- 17213500
TI  - Breaching the security of the Kaiser Permanente Internet patient portal: the
      organizational foundations of information security.
AB  - This case study describes and analyzes a breach of the confidentiality and
      integrity of personally identified health information (e.g. appointment details,
      answers to patients' questions, medical advice) for over 800 Kaiser Permanente
      (KP) members through KP Online, a web-enabled health care portal. The authors
      obtained and analyzed multiple types of qualitative data about this incident
      including interviews with KP staff, incident reports, root cause analyses, and
      media reports. Reasons at multiple levels account for the breach, including the
      architecture of the information system, the motivations of individual staff
      members, and differences among the subcultures of individual groups within as
      well as technical and social relations across the Kaiser IT program. None of
      these reasons could be classified, strictly speaking, as "security violations."
      This case study, thus, suggests that, to protect sensitive patient information,
      health care organizations should build safe organizational contexts for complex
      health information systems in addition to complying with good information
      security practice and regulations such as the Health Insurance Portability and
      Accountability Act (HIPAA) of 1996.

PMID- 17213501
TI  - A day in the life of PubMed: analysis of a typical day's query log.
AB  - OBJECTIVE: To characterize PubMed usage over a typical day and compare it to
      previous studies of user behavior on Web search engines. DESIGN: We performed a
      lexical and semantic analysis of 2,689,166 queries issued on PubMed over 24
      consecutive hours on a typical day. MEASUREMENTS: We measured the number of
      queries, number of distinct users, queries per user, terms per query, common
      terms, Boolean operator use, common phrases, result set size, MeSH categories,
      used semantic measurements to group queries into sessions, and studied the
      addition and removal of terms from consecutive queries to gauge search
      strategies. RESULTS: The size of the result sets from a sample of queries showed
      a bimodal distribution, with peaks at approximately 3 and 100 results, suggesting
      that a large group of queries was tightly focused and another was broad. Like Web
      search engine sessions, most PubMed sessions consisted of a single query.
      However, PubMed queries contained more terms. CONCLUSION: PubMed's usage profile
      should be considered when educating users, building user interfaces, and
      developing future biomedical information retrieval systems.

PMID- 17213502
TI  - A comparative evaluation of full-text, concept-based, and context-sensitive
      search.
AB  - OBJECTIVES: Study comparatively (1) concept-based search, using documents pre
      indexed by a conceptual hierarchy; (2) context-sensitive search, using
      structured, labeled documents; and (3) traditional full-text search. Hypotheses
      were: (1) more contexts lead to better retrieval accuracy; and (2) adding concept
      based search to the other searches would improve upon their baseline
      performances. DESIGN: Use our Vaidurya architecture, for search and retrieval
      evaluation, of structured documents classified by a conceptual hierarchy, on a
      clinical guidelines test collection. MEASUREMENTS: Precision computed at
      different levels of recall to assess the contribution of the retrieval methods.
      Comparisons of precisions done with recall set at 0.5, using t-tests. RESULTS:
      Performance increased monotonically with the number of query context elements.
      Adding context-sensitive elements, mean improvement was 11.1% at recall 0.5. With
      three contexts, mean query precision was 42% +/- 17% (95% confidence interval
      [CI], 31% to 53%); with two contexts, 32% +/- 13% (95% CI, 27% to 38%); and one
      context, 20% +/- 9% (95% CI, 15% to 24%). Adding context-based queries to full
      text queries monotonically improved precision beyond the 0.4 level of recall.
      Mean improvement was 4.5% at recall 0.5. Adding concept-based search to full-text
      search improved precision to 19.4% at recall 0.5. CONCLUSIONS: The study
      demonstrated usefulness of concept-based and context-sensitive queries for
      enhancing the precision of retrieval from a digital library of semi-structured
      clinical guideline documents. Concept-based searches outperformed free-text
      queries, especially when baseline precision was low. In general, the more
      ontological elements used in the query, the greater the resulting precision.

PMID- 17213504
TI  - The way women perceive teratogenic risk.

PMID- 17213505
TI  - Inactive pharmaceutical ingredients : implications for pregnancy.

PMID- 17213506
TI  - Drugs in pregnancy: acknowledging challenges--finding solutions.

PMID- 17213507
TI  - Challenges in drug use near term and during delivery.

PMID- 17213508
TI  - Collection and analysis of drug safety data in pregnancy.

PMID- 17213510
TI  - Drugs used in pregnancy: the regulatory process.

PMID- 17213509
TI  - 45 years later...where do we stand?

PMID- 17213511
TI  - The curse of dengue.

PMID- 17213512
TI  - Chikungunya fever: clinical manifestations & management.

PMID- 17213513
TI  - Vector biology of dengue & chikungunya viruses.

PMID- 17213514
TI  - Addressing the diabetes pandemic: a comprehensive approach.

PMID- 17213515
TI  - Whither autologous blood predonations?

PMID- 17213516
TI  - Protect the health of health care workers.

PMID- 17213517
TI  - Hepatoprotective herbal drug, silymarin from experimental pharmacology to
      clinical medicine.
AB  - Silymarin, a flavonolignan from 'milk thistle' (Silybum marianum) plant is used
      almost exclusively for hepatoprotection and amounts to 180 million US dollars
      business in Germany alone. In this review we discuss about its safety, efficacy
      and future uses in liver diseases. The use of silymarin may replace the
      polyherbal formulations and will avoid the major problems of standardization,
      quality control and contamination with heavy metals or bacterial toxins.
      Silymarin consists of four flavonolignan isomers namely--silybin, isosilybin,
      silydianin and silychristin. Among them, silybin being the most active and
      commonly used. Silymarin is orally absorbed and is excreted mainly through bile
      as sulphates and conjugates. Silymarin offers good protection in various toxic
      models of experimental liver diseases in laboratory animals. It acts by
      antioxidative, anti-lipid peroxidative, antifibrotic, anti-inflammatory, membrane
      stabilizing, immunomodulatory and liver regenerating mechanisms. Silymarin has
      clinical applications in alcoholic liver diseases, liver cirrhosis, Amanita
      mushroom poisoning, viral hepatitis, toxic and drug induced liver diseases and in
      diabetic patients. Though silymarin does not have antiviral properties against
      hepatitis virus, it promotes protein synthesis, helps in regenerating liver
      tissue, controls inflammation, enhances glucuronidation and protects against
      glutathione depletion. Silymarin may prove to be a useful drug for
      hepatoprotection in hepatobiliary diseases and in hepatotoxicity due to drugs.
      The non traditional use of silymarin may make a breakthrough as a new approach to
      protect other organs in addition to liver. As it is having a good safety profile,
      better patient tolerability and an effective drug at an affordable price, in near
      future new derivatives or new combinations of this drug may prove to be useful.

PMID- 17213518
TI  - Feasibility of pre-operative autologous blood donation in Indian patients with
      elective orthopaedic surgery.
AB  - BACKGROUND & OBJECTIVES: Pre-operative autologous blood donation (PABD) in
      elective orthopaedic surgeries is a well known procedure in the West. We
      initiated this programme at a tertiary care hospital in north India to study its
      feasibility in Indian patients. METHODS: In a prospective case-control study, 144
      patients undergoing primary total hip or knee replacement, inter-vertebral
      discectomy, mal-union and non-union reconstruction were educated and motivated to
      pre-donate. Patients fulfilling the inclusion criteria and making autologous
      donation formed the PABD group (n=22). Patients eligible for PABD, but unwilling
      to participate; age, sex, pre-operative haemoglobin and operative procedure
      matched acted as controls (n=27). Unit(s) collected was processed like an
      allogeneic unit. Unit(s) found reactive for infectious markers or not utilized
      was discarded. Mean blood losses, transfusion trigger, allogeneic exposure and
      wastage between the two groups were compared. RESULTS: Of the 144 patients
      motivated, 40 per cent of the eligible subjects pre-deposited. The main
      motivational factor was fear of getting infection from someone's blood. Cardiac
      events and anaemia prevented 61.8 per cent patients to participate. Of the 50
      units ordered, autologous units with a mean of 1.4 units/patient contributed 62
      per cent. For total hip and total knee replacement (THR and TKR), autologous
      units met 76.2 and 80 per cent respectively of the total blood requirement. A
      significant decrease in the allogeneic exposure was observed between PABD and
      control group (18.2 vs 66.7%); 32.3 per cent of the autologous units were
      discarded. INTERPRETATION & CONCLUSION: Comprehensive PABD programme may be an
      effective method for reducing the need for allogeneic transfusion in patients
      undergoing joint replacement surgeries in our country, where transfusion
      transmitted infections due to high percentage of replacement donations and lack
      of sensitive assays for testing are still a cause for concern.

PMID- 17213519
TI  - Injection practices in the formal & informal healthcare sectors in rural north
      India.
AB  - BACKGROUND & OBJECTIVES: Unsafe injections in health settings contribute to a
      large burden of preventable blood-borne diseases. Current strategies to enhance
      injection safety in India almost exclusively target the formal health sector.
      However, injections are provided not only by doctors and nurses in the formal
      sector, but also by practitioners from the informal sector, such as traditional
      healers, who are not necessarily trained or authorized to administer these. The
      present study was undertaken to determine the extent to which patients using
      formal healthcare services also consult and receive injections in the informal
      sector, quantify the injections received by these patients and their relatives,
      and assess knowledge and attitudes in relation to injections. METHODS: A cross
      sectional survey of 280 in patients and 120 of their relatives was undertaken
      between November 2004 and February 2005 in two rural hospitals in Bihar and
      Jharkhand states. RESULTS: Sixty one per cent of patients had consulted a
      healthcare practitioner in the month prior to admission, and 39 per cent of these
      had consulted in the informal sector at least once. Forty three per cent had
      received at least one injection in the month prior to admission, and 43 per cent
      of these were given by informal practitioners. About 13 per cent of relatives had
      received at least one injection in the last three months, 69 per cent of which
      were given by informal practitioners. Thirty per cent did not know that unsafe
      injections can spread diseases. INTERPRETATION & CONCLUSION: The findings of this
      survey highlight the fact that informal practitioners in India are commonly
      administering injections with clear implications for patient safety. There is a
      need to promote strategies for injection safety among both formal and informal
      practitioners.

PMID- 17213520
TI  - Correlation between methotrexate efficacy & toxicity with C677T polymorphism of
      the methylenetetrahydrofolate gene in rheumatoid arthritis patients on folate
      supplementation.
AB  - BACKGROUND & OBJECTIVES: C677T polymorphism in the methylenetetrahydrofolate
      reductase (MTHFR) gene has been proposed as a pharmacogenomic marker for toxicity
      of methotrexate (MTX). We studied the relationship between the C677T gene
      polymorphism and toxicity and efficacy of MTX in patients with rheumatoid
      arthritis (RA) on folate supplementation. METHODS: A total of 150 RA patients
      fulfilling American College of Rheumatology (ACR) criteria and on MTX treatment
      were evaluated. The mean age of the patients was 42.9 +/- 11.1 yr, mean disease
      duration was 7.65 +/- 5.2 yr and the mean duration of MTX treatment was 26.1 +/-
      20.6 months. Genotype analysis of MTHFR gene was done by PCR and restriction
      enzyme method. Primary endpoint for treatment efficacy was change in disease
      activity score 28 (DAS28) from baseline. Drug toxicity was evaluated by blood
      count, renal and liver function tests and a standardized questionnaire. RESULTS:
      The mean DAS at baseline was 5.02 +/- 0.8. All patients received 10 mg/wk folic
      acid supplementation. Forty two per cent (63/150) of the patients had C677T
      polymorphism of which 4 were homozygous (T/T) and 59 were heterozygous (C/T). The
      baseline characteristics of the patients with or without polymorphism were
      comparable. The frequency of adverse events was not increased in patients with
      C677T polymorphism with 11 patients experiencing adverse events as compared to 19
      in the group without polymorphism (of whom 4 and 7 patients respectively
      discontinued treatment). The C677T polymorphism was not associated with any
      difference in response to treatment. INTERPRETATION & CONCLUSION: Our findings
      suggest that C677T polymorphism in the MTHFR gene is not predictive of toxicity
      or efficacy of MTX treatment in RA patients receiving folate supplementation.
      Further studies need to be done to look at polymorphisms in other enzymes that
      may have association with MTX clinical efficacy and toxicity.

PMID- 17213521
TI  - Insulin resistance & secretion in subjects with normal fasting plasma glucose.
AB  - BACKGROUND & OBJECTIVES: Lowering the diagnostic threshold of normal fasting
      plasma glucose (FPG) from 6.1 to 5.56 mmol/l has been proposed by American
      Diabetes Association. As early detection of subjects with risk of diabetes is
      important, it is crucial to understand the relationship between different levels
      of FPG, insulin resistance (IR) and insulin secretion. We measured IR and insulin
      secretion in subjects with different levels of FPG to investigate the
      relationship between FPG and IR and insulin secretion, and to see whether
      lowering the cut-off improves the sensitivity of impaired fasting glucose to
      predict diabetes. METHODS: Apparently healthy subjects (294) were enrolled and
      divided into 3 groups according to their FPG levels; group 1 (<5.56 mmol/l,
      n=129), group 2 (5.56-6.09 mmol/l, n=99) and group 3 (6.1-6.9 mmol/l, n=66).
      Steady state plasma glucose (SSPG) derived from insulin suppression test was used
      to quantify insulin resistance and 30 min insulinogenic index during an oral
      glucose tolerance test to measure acute insulin secretion. RESULTS: The blood
      pressure was higher in group 3 than group 2 and fasting plasma insulin and
      triglyceride were higher in group 3 than that in group 1. The insulinogenic index
      was higher in the group 1 than group 3 and the SSPG was significantly higher in
      group 3 compared to group 1. INTERPRETATION & CONCLUSION: Our study showed a
      trend of progressive deterioration of both insulin action and secretion with
      increasing FPG level. These are supportive evidences for lowering the FPG to 5.56
      mmol/l as suggested by the ADA.

PMID- 17213522
TI  - Effect of environmental iodine deficiency (EID) on foetal growth in Nigeria.
AB  - BACKGROUND & OBJECTIVES: There is scarcity of information on impact of iodine
      deficiency on growth and development of newborns, both pre-term and term babies.
      The present study was carried out to see the impact of iodine deficiency (ID) on
      the intrauterine foetal growth and development in terms of birth weight (BW) in
      an African population living in an iodine deficient zone. METHODS: The maternal
      and cord serum thyroid parameters at term delivery (38-40 wk of gestation) were
      measured and correlated with the birth weights of the corresponding newborns, and
      the results compared between those assessed in an ID zone (Jengere region of
      Bassa district, Plateau State, Nigeria) and with that of non ID (Control) zone,
      Jos, the State capital. RESULTS: The level of maternal and neonatal thyroid
      function were significantly reduced in the group with low birth weights (<2.5 kg)
      as compared to the level seen in normal birth weights category in both control
      (Jos) and ID (Jengere) regions. Both in non ID and ID regions the maternal serum
      thyroxine (T4), thyroxine binding globulin (TBG) and free thyroxine index (FT4I)
      were positively correlated (P<0.005) with BW of term babies while thyroid
      stimulating hormone (TSH) (P<0.005) and thyroxine binding capacity (TBK) (P<0.05)
      showed negative correlation. Maternal T3 and T3/T4 ratio did not show any
      correlation with BW in Jos, while in the ID region of Bassa the BW showed a
      positive correlation (P<0.005) with the maternal serum T3 and T3/T4 ratio. Cord
      serum analysis of the term babies revealed that the BW was positively correlated
      with its T4, triiodothyronine (T3), TBG, FT4I and T4/TBG ratio (Jos only)
      (P<0.005) in both ID region of Bassa and non ID control zone of Jos. Cord serum
      TSH and TBK showed negative correlation (P<0.005) with BW. Thyrotrophin releasing
      hormone (TRH) stimulation test revealed that mothers with small for date (SFD)
      babies at term were more hypothyroid compared to the level of thyroid function
      seen in the women delivering normal babies. INTERPRETATION & CONCLUSION: Maternal
      thyroid hormone plays a significant role in the intrauterine foetal growth and
      development, and the smaller babies and their corresponding mothers, in an ID
      affected area are functionally sub-thyroid in greater proportion due to
      prevailing long standing environmental iodine deficiency (EID). Maternal T3 is an
      important factor in the defence of foetus in ID regions.

PMID- 17213523
TI  - Assessment of mammographic density changes on plain film mammograms in
      postmenopausal women on hormone replacement therapy.
AB  - BACKGROUND & OBJECTIVES: Mammographic screening is an effective tool for the
      early detection of breast cancer. Hormone replacement therapy (HRT) has been
      shown to increase mammographic density and thus may hinder early detection of
      small tumours. We undertook this study to determine and compare the frequency and
      degree of change in mammographic density in postmenopausal women in HRT using two
      different methods: the classical Wolfe classification and a new semiquantitative
      method, which we named as the comparison wheel. METHODS: This study included 285
      women, 206 under hormone treatment, and 79 control subjects. All women underwent
      baseline mammographic study before the beginning of treatment. Mean interval of
      the follow up mammograms was 16 months. The methods were compared in evaluating
      the effects of three types of hormone therapies on mammographic density. RESULTS:
      The frequency of change was only significant in the combined hormone replacement
      group when Wolfe classification was used. However, the frequency of increase in
      density (estrogen group 21%, combined therapy group 42%, tibolone group 28%) was
      markedly higher when the comparison wheel was used. The inter-rater Kappa value
      was calculated as 0.977 for the first and 0.957 for the second readings of the
      two radiologists for the comparison wheel, and 0.973 and 0.968 for the Wolfe
      classification. The intra-rater Kappa values were determined as 0.972 and 0.957
      for the first and and 0.963 and 0.926 for the second radiologist for comparison
      wheel and Wolfe classification respectively. INTERPRETATION & CONCLUSION: Our
      findings indicate that the estimated increase of mammographic density depends on
      the selected hormone regimen, as well as the method of evaluation. The comparison
      wheel is a semiquantitative method of evaluating changes of mammographic density
      and is sensitive and reproducible with high inter- and intra-rater Kappa values.
      This method can be used as an alternative for comparison of digital mammographic
      applications in the future.

PMID- 17213525
TI  - Changing trends in sexually transmitted infections at a Regional STD Centre in
      north India.
AB  - BACKGROUND & OBJECTIVES: Sexually transmitted infections (STIs) a major public
      health problem in India show various trends in different parts of the country.
      However, there are limited data on the changing profile of laboratory proven STIs
      in the same clinic over the years. The present study was thus aimed to determine
      the changing trends of the profile of STIs and HIV seropositivity in STD clinic
      attendees over a 15 yr period, and also to detect change, if any, in the
      antimicrobial resistance pattern of Neisseria gonorrhoeae. METHODS: The STIs were
      diagnosed clinically and confirmed by standard laboratory techniques. Socio
      demographic data were collected through pre-designed proformae. The STI profile
      and HIV seropositivity were compared between 1990-1993 (A), 1994-1997 (B), 1998
      2001 (C) and 2002-2004 (D). Antimicrobial resistance pattern of N. gonorrhoeae
      was determined by standard techniques and compared between the last three
      periods. RESULTS: Of the 78,617 STD attendees, 12,709 (16.2%) had STIs. During
      period A, genital discharges and during B, C and D, genital ulcerative diseases
      were predominant. Syphilis was the commonest STI. There was significant rise in
      the cases of syphilis, herpes progenitalis and genital warts and reduction in
      that of chancroid, lymphogranulomavenereum (LGV), donovanosis, candidiasis,
      trichomoniasis and bacterial vaginosis cases. The number of cases with primary
      syphilis diminished significantly (P<0.001), with a concomitant rise in secondary
      and early latent syphilis. A rising trend was observed in the HIV seropositivity
      during the different periods. The association of HIV seropositivity was
      consistently more in patients presenting with genital ulcers specially syphilis,
      and rose significantly from A (0.6%) to C (8.8%), but became stationary during D.
      A drastic change in the antimicrobial resistance of N. gonorrhoeae from B to C
      and C to D and the emergence of less sensitive isolates to ceftriaxone during the
      later part of the study were observed. INTERPRETATION & CONCLUSION: Our study
      showed a definite changing trend in the profile of STIs in the clinic attendees
      of a major STD centre during a 15 yr period. However, the significant rise in the
      cases of viral STIs and syphilis contrasted with reduction in the rest.

PMID- 17213524
TI  - Immune status of health care personnel & post vaccination analysis of immunity
      against rubella in an eye hospital.
AB  - BACKGROUND & OBJECTIVES: Congenital rubella syndrome (CRS) accounts for a
      significant amount of mortality and morbidity in India. Rubella vaccination is
      not included in our national immunization programme. Occupational exposure of the
      health care personnel to rubella infection is well known. This study aims to
      assess the serological status of health care workers against rubella virus in
      Aravind Eye Care System, Madurai and to follow the immune response in the
      seronegative individuals after vaccination. METHODS: A total of 500 female and 81
      male workers were enrolled in the study. Blood sample was collected for the
      analysis of rubella specific IgM and IgG antibodies. The seronegative individuals
      were vaccinated with monovalent rubella vaccine, RA 27/3. The post-vaccination
      samples were analysed for the antibody levels and their avidity using enzyme
      immunoassay. RESULTS: Of the 581 volunteers, 493 were seropositive with good
      protective immunity and 22 had both IgM and IgG antibodies. Sixty six volunteers
      (59 females and 7 males) were found to be seronegative to rubella. The
      seroconversion was observed in all the sixty vaccinated individuals, as seen by
      the appearance of anti-rubella IgG antibodies by fourth week, reaching the peak
      protective levels (>20 IU/ml) by third month. There was also a progressive
      increase in the avidity after vaccination. INTERPRETATION & CONCLUSION: Nearly
      11.4 per cent of the health care workers were found to be seronegative for
      rubella virus and after vaccination, these volunteers developed a good protective
      immunity, thereby reducing the risk of contracting the hospital based rubella
      infection. Therefore, rubella vaccination may be instituted in hospitals for the
      benefit of health care workers.

PMID- 17213526
TI  - Immunoreactive outer membrane proteins of Leptospira interrogans serovar Canicola
      strain Hond Utrecht IV.
AB  - BACKGROUND & OBJECTIVES: Leptospirosis is a severe and complex zoonotic disease
      prevalent in many countries including India. Current leptospiral research is
      focussed on the identification of the outer membrane proteins (OMPs) of the
      organism that could be used in developing diagnostic assays for leptospirosis.
      METHODS: The Leptospira interrogans serovar Canicola was grown in EMJH medium and
      the cells were subjected to sarcosyl detergent treatment. The sarcosyl soluble
      (SS) and sarcosyl insoluble (SI) fractions were analyzed by SDS-PAGE and
      immunoblotting to deduce their protein profile and identifying various
      immunodominant antigens. RESULTS: The protein profile of SS fractions indicated
      the presence of three major bands of 41, 32 and 25 kDa and minor bands of 85 and
      46 kDa. The SI fraction in serovar Canicola revealed the presence of 112, 93, 77,
      43, 36, 29 and 22.5 kDa as major bands and minor bands of 102 and 53 kDa. In
      immunoblotting, the SS proteins of 41, 32 and 25 kDa and SI proteins of 112, 77,
      36 and 22.5 kDa were detected to be major immunogenic proteins. INTERPRETATION &
      CONCLUSION: In our study immunogenic proteins were extracted from SS and SI
      fractions and OMPs were similar to those reported in other pathogenic Leptospira
      strains. These OMPs being unique to all the pathogenic leptospires, can be
      targeted for diagnostic purpose. Further analysis of the cellular location and
      expression of leptospiral proteins will be useful in the annotation of genomic
      sequence data and in providing insight into the biology of Leptospira cells.

PMID- 17213527
TI  - Rapid detection of enterotoxigenic Bacteroides fragilis in diarrhoeal faecal
      samples.
AB  - BACKGROUND & OBJECTIVES: Enterotoxigenic Bacteroides fragilis (ETBF) is an
      important aetiological agent of acute diarrhoeal illness in humans. It is a
      fastidious anaerobe and takes 3-5 days when grown in culture, and test for
      enterotoxin detection requires additional time conventionally. The present study
      was aimed to standardize a rapid and sensitive diagnostic assay and to screen the
      presence of ETBF isolates directly in faecal samples using polymerase chain
      reaction (PCR) technique. METHODS: A total of 85 faecal samples were processed
      for both aerobic and anaerobic bacterial isolation by culture technique and also
      subjected to PCR, for amplification of neuraminidase and enterotoxin genes of B.
      fragilis using specific primers. RESULTS: PCR was found to be positive for
      neuraminidase gene in 14/65 (21.5%) and for both neuraminidase and enterotoxin
      genes in 4/65 (6.1%) faecal samples within 48 h in study group. B. fragilis did
      not grow in any of the faecal samples when cultured anaerobically. However, the
      delay in transport and processing of faecal samples for anaerobic culture may be
      responsible for culture negativity. INTERPRETATION & CONCLUSION: PCR assay can be
      used as a rapid and sensitive diagnostic tool for the identification of ETBF in
      culture as well as directly from diarrhoeal faecal samples instead of using
      conventional technique. The association of ETBF in diarrhoeal diseases is unclear
      and importance of ETBF as a causal agent will require more studies in Indian
      population.

PMID- 17213528
TI  - Skewed sex ratio in India.

PMID- 17213529
TI  - Fluoroquinolone resistance among Salmonella enterica serovar Paratyphi A in
      Pondicherry.

PMID- 17213530
TI  - Antimicrobial resistance profile of Pseudomonas aeruginosa producing metallo-beta
      lactamases.

PMID- 17213531
TI  - Current outbreak of hepatitis A in Bulgaria, 2006.

PMID- 17213532
TI  - Outbreak of enteroviral meningitis in Latvia, August-October 2006.

PMID- 17213533
TI  - Personal (non-pharmaceutical) protective measures for reducing transmission of
      influenza--ECDC interim recommendations.

PMID- 17213534
TI  - Cluster of measles cases in the Roma/Sinti population, Italy, June-September
      2006.
AB  - Three clusters of measles cases occurred between June and September 2006, in the
      Roma/Sinti populations in three different Italian regions: the Bolzano-South
      Tyrol in northern Italy; Lazio in central Italy; and the island of Sardinia in
      the southwest.

PMID- 17213536
TI  - Unexplained summer increase in non-travel-related legionellosis in the UK and
      Netherlands.

PMID- 17213535
TI  - Outbreak of legionellosis suspected to be related to a whirlpool spa display,
      September 2006, Lorquin, France.

PMID- 17213537
TI  - Coordinated European actions to prevent and control norovirus outbreaks on cruise
      ships.

PMID- 17213538
TI  - Hepatitis A cases in a travelling community in southeast England.

PMID- 17213539
TI  - Analysis of 721 Chlamydia trachomatis-positive urogenital specimens from men and
      women using lymphogranuloma venereum L2-specific real-time PCR assay.

PMID- 17213540
TI  - No link established between deaths in elderly patients in Israel and influenza
      vaccination.

PMID- 17213541
TI  - An outbreak of Salmonella enteritidis infections linked to a restaurant in Riga,
      August 2006.

PMID- 17213542
TI  - Surveillance methods and case definition for extensively drug resistant TB (XDR
      TB) and relevance to Europe: summary update.

PMID- 17213543
TI  - Potential rabies exposure after a bat bite, Denmark, June 2006.

PMID- 17213544
TI  - Increase in viral meningitis cases reported in the Autonomous Region of Madrid,
      Spain, 2006.

PMID- 17213547
TI  - Dr Margaret Chan appointed WHO Director-General.

PMID- 17213548
TI  - A variant of Chlamydia trachomatis with deletion in cryptic plasmid: implications
      for use of PCR diagnostic tests.

PMID- 17213549
TI  - Vibrio alginolyticus infections in the Netherlands after swimming in the North
      Sea.

PMID- 17213550
TI  - Mumps outbreak in young adults following a village festival in the Navarra
      region, Spain, August 2006.

PMID- 17213551
TI  - Trichinella in pork: current knowledge on the suitability of freezing as a public
      health measure.

PMID- 17213552
TI  - Unexplained increase in Paecilomyces variotii blood culture isolates in the UK.

PMID- 17213553
TI  - A case of autochthonous Plasmodium vivax malaria, Corsica, August 2006.

PMID- 17213554
TI  - Pneumococcal conjugate vaccine is efficacious against invasive disease with fewer
      doses than currently recommended.

PMID- 17213555
TI  - HIV/AIDS in Europe: trends and EU-wide priorities.

PMID- 17213556
TI  - Ongoing HIV and viral hepatitis infections in IDUs across the EU, 2001-2005.

PMID- 17213557
TI  - Comparable strategies needed to evaluate human papillomavirus vaccine efficiency
      across Europe.

PMID- 17213558
TI  - Salmonella contamination in non-UK produced shell eggs on retail sale in some
      regions of England.

PMID- 17213559
TI  - Hajj 2007: vaccination requirements and travel advice issued.

PMID- 17213560
TI  - Two unrelated cases of septicaemia due to Vibrio cholerae non-O1, non-O139 in
      Poland, July and August 2006.

PMID- 17213562
TI  - Impact of a genetic variant of Chlamydia trachomatis on national detection rates
      in Sweden.

PMID- 17213561
TI  - Legionnaires' disease: when an 'outbreak' is not an outbreak.
AB  - During August 2006, there was a large increase in non-travel related legionella
      cases throughout England and in the Netherlands.

PMID- 17213563
TI  - Third case of vCJD reported in the United States.

PMID- 17213564
TI  - Use of 7-valent pneumococcal conjugate vaccine in EU.

PMID- 17213565
TI  - Increase in norovirus activity reported in Europe.

PMID- 17213566
TI  - Increase in norovirus circulation in Hungary in October-November 2006.

PMID- 17213567
TI  - Plasmodium falciparum malaria in Jamaica, October-December 2006.

PMID- 17213568
TI  - Outbreak of foodborne botulism linked to barbecue, Austria, 2006.

PMID- 17213569
TI  - Highly pathogenic avian influenza A/H5N1-update and overview of 2006.

PMID- 17213570
TI  - Soft tissue infections in Belgian rugby players due to Streptococcus pyogenes emm
      type 81.

PMID- 17213571
TI  - Epidemic intelligence during mass gatherings.

PMID- 17213572
TI  - Cooperation between animal and human health sectors is key to the detection,
      surveillance, and control of emerging disease: IMED 2007 meeting in Vienna,
      February 2007.

PMID- 17213573
TI  - Angiotensin II and insulin crosstalk in the cardiovascular system.
AB  - Under normal physiology, insulin exerts vasodilatory and pro-survival actions via
      the phosphatidylinositol 3-kinase (PI3-kinase) pathway and vasoconstrictive and
      mitogenic actions via the mitogen-activated protein kinase (MAPK) pathway in the
      vasculature. In the insulin resistant states, insulin signals through the PI3
      kinase pathway are blunted but its signals through the MAPK cascade remain
      intact. This imbalance predisposes insulin resistant patients to hypertension and
      atherosclerosis. The renin-angiotensin system (RAS) is expressed both
      systemically and locally in the cardiovascular system. Insulin resistance up
      regulates the local RAS which contributes to the pathogenesis of hypertension,
      heart failure, and atherosclerosis. Angiotensin II impairs insulin signaling,
      induces inflammation via the NF-kappaB pathway, reduces nitric oxide availability
      and facilitates vasoconstriction, leading to insulin resistance and endothelial
      dysfunction. Thus the RAS, insulin resistance and inflammation perpetuate each
      other and coordinately contribute to endothelial dysfunction, vascular injury and
      atherosclerosis. RAS inhibition decreases cardiovascular and renal morbidity and
      mortality and the incidence of new onset Type 2 diabetes.

PMID- 17213574
TI  - Type 1 diabetes and latent autoimmune diabetes in adults.
AB  - The review is aimed to explore the clinical and pathogenic spectrum of autoimmune
      diabetes including Type 1 diabetes and latent autoimmune diabetes in adults
      (LADA). Genetic susceptibility modifies age at onset in autoimmune diabetes. The
      most important genetic susceptibility to Type 1 diabetes and LADA is in the HLA
      region. Because of the age-related genetic factors, LADA can not be distinguished
      from classic Type 1 diabetes by genetics. Non-genetic factors contribute much to
      Type 1 diabetes, but little is known in LADA. Diabetes-associated immune process
      can occur in early childhood and can be predictive of an ongoing beta cell
      destruction. The management and prevention of LADA need to be investigated in
      order to define the best therapeutic strategy.

PMID- 17213575
TI  - Effect of variation in 5'-regulatory region of insulin receptor substrate-1 gene
      on gene expression.
AB  - OBJECTIVE; To determine the effect of a variation of CAG-rich region, which was
      found in the 5'-regulatory sequence of insulin receptor substrate-1(IRS-1) gene
      in Type 2 diabetes mellitus(T2DM) patients, on gene expression and its mechanism.
      METHODS: The recombinants, pGL2.P-T3 and pGL2.P-T5, were constructed with
      luciferase reporter vector, pGL2 promoter. T3 and T5 were wild-type and variant
      alleles, respectively. The recombinants were cotransfected with pSV-beta
      galactosidase control vector to Hela cells. Luciferase assay was performed to
      assess transcriptional activity. The electrophoresis mobility shift assay(EMSA)
      and DNA footprint assay were applied to determine the interaction between the DNA
      regulatory sequences and nuclear proteins of Hela cells. RESULTS: The relative
      transcription activity of T5 was lower than that of T3 [(7.76+/-1.05)% vs (9.98+/
      1.40)%, P<0.05]; EMSA showed both T3 and T5 formed a single retarded band in gel
      with the same mobility with nuclear proteins; T5 had 2 binding sites for
      transacting factors, CGCGCCCGCGGGCGGCGGC and GGGCGGCTGGTGGCGGCTG, which was the
      same as T3. CONCLUSION: Although the variation in T5 do not alter the DNA-binding
      sites for Hela cell nuclear extracts, the notable decrease in gene transcription
      activity induced by it may be an important factor to the development T2DM in the
      carrier.

PMID- 17213576
TI  - [Cross-sectional study of the relation between carboxypeptidase-H antibody and
      islet beta cell function in patients with latent autoimmune diabetes in adults].
AB  - OBJECTIVE: To explore the relation between carboxypeptidase-H antibody (CPH-Ab)
      and islet beta cell function in patients with latent autoimmune diabetes in
      adults (LADA) and to further confirm the diagnostic value of CPH-Ab for LADA.
      METHODS: Five hundred and forty-five patients who were initially diagnosed as
      Type 2 diabetes mellitus (T2DM) were tested with CPH-Ab and GAD-Ab by radioligand
      assay (RLA). T2DM patients, according to CPH-Ab and GAD-Ab status, were divided
      into CPH-Ab(+) group, GAD-Ab(+) group, and Ab(-) group to compare their islet
      beta cell function [represented by fasting C-peptide (FCP) and 2h postprandial C
      peptide (2hCP)]. The relation between CPH-Ab and islet beta cell function in LADA
      was analyzed. RESULTS: The fasting C-peptide level in CPH-Ab(+) patients was
      between that of GAD-Ab(+) patients and that of Ab(-) patients (P<0.05), and the
      difference was still significant when the 3 groups were stratified with duration
      of disease (All P<0.05), but not with body mess index (all P>0.05). Corrected by
      concomitant variables including age, age at onset, duration of disease, and sex,
      the differences among the 3 groups were statistically significant (both P<0.001).
      Among the 3 groups FCP was lower than Ab(-) group in CPH-Ab(+) (P<0.05) and both
      FCP and PCP were lower than Ab(-) group in GAD-Ab(+) group (P<0.05 and P<0.01).
      The proportions of patients with insulin deficiency in CPH-Ab(+), GAD-Ab(+), and
      Ab(-) group were 27.6% (8/29), 48.1% (8/52) and 13.5% (54/400), respectively,
      which were significantly different among the 3 groups (P<0.001). GAD-Ab, BMI, and
      fasting blood glucose had effects on FCP and PCP in T2DM patients (All P<0.05),
      while CPH-Ab did not enter the equation in multivariable stepwise regressive
      analysis (P>0.05). CONCLUSION: The effect of CPH-Ab is less marked than that of
      GAD-Ab on islet beta-cell function in LADA patients. The value of CPH-Ab for the
      failure of islet beta-cell function in LADA should be determined prospectively.

PMID- 17213577
TI  - [Effect of plasma glucose on the vascular endothelial function and analysis of
      relevant factors].
AB  - OBJECTIVE: To compare the flow-mediated dilatation (FMD) among the newly
      diagnosed impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), and
      the normal controls (NC) and to analyze relevant factors under different glucose
      levels. METHODS: The study included IGT (n=34), DM1 (n=52), DM2 (n=33) and NC
      (n=25). Levels of fasting plasma glucose (FPG), 2-hour postprandial plasma
      glucose (PPG), fasting insulin (FINS), 2-hour postprandial insulin (PINS),
      triglyceride (TG), total cholesterol (TC), and hemoglobin A1C (HbA1C) were
      determined in all participants. High resolution ultrasound examining FMD was
      performed to measure vascular endothelial function subsequently. RESULTS: There
      was statistically significant difference between IGT, DM, HG and NC group in FMD
      (P=0.008). Partial correlation analysis found that a significant negative
      correlation existed between FMD and homeostasis model assessment-index (HOMA
      IRI), difference of plasma glucose (DPG), FPG and PPG (P<0.01), and a negative
      correlation between FMD and HbA1C (P<0.05). Setting FMD as dependent variable to
      conduct multiple linear stepwise regression, in IGT group it was the waist/hip
      ratio (WHR) and HOMA-IRI that entered the regression equation; in DM1 group it
      was HOMA-IRI, PPG and DPG that entered the regression equation; in DM2 group it
      was FPG and HOMA-beta that entered the regression equation. CONCLUSION: There
      exists a flow-mediated vasodilatation dysfunction in patients of newly diagnosed
      IGT and T2DM. Effect of relevant factors on FMD differs with different glucose
      levels.

PMID- 17213578
TI  - [Effect of complete Freund's adjuvant on islet beta cell apoptosis and its
      mechanism in non-obese diabetic mice].
AB  - OBJECTIVE: To investigate the effect of complete Freund's adjuvant (CFA) on islet
      beta cell apoptosis in preventing diabetes in non-obese diabetic (NOD) mice, and
      the influence on apoptotic related-gene expression. METHODS: Four-week-old female
      NOD mice were randomly divided into Group CFA (n=5) and Group saline (NS) control
      (n=5). Mice in Group CFA were injected in the hind footpad with 50 microL CFA and
      mice in Group NS with 50 microL NS. Blood sugar was monitored and diabetes was
      diagnosed if blood sugar was higher than 11.1 mmol/L for 2 continuous days in the
      NOD mice. The mice were sacrificed when diagnosed as diabetes or at 30 weeks of
      age. Pancreatic sections were made for: evaluation of insulitis severity with HE
      staining; counting of apoptotic beta cells with the terminal deoxynucleotidyl
      transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL) method,
      and ABC immunohistochemical double labeling; counting of Fas, FasL and Bcl-x
      positive cells respectively with ABC immunohistochemical method. RESULTS: By 30
      weeks of age, none of the 5 CFA-treated mice, compared with 3 of the 5 control
      mice, had developed diabetes. The insulitis score was lower (1.820+/-0.962 vs.
      3.020+/-1.040, P<0.05), the rates of apoptotic beta cells, Fas positive cells and
      FasL positive cells were lower [(10.2+/-2.8)% vs. (15.9+/-6.5)%, (54.9+/-14.5)%
      vs. (75.7+/-12.9)%, (20.3+/-10.4)% vs. (27.9+/-12.0)%, P<0.05), and the Bcl-x
      positive cell rate was higher [(74.9+/-10.7)% vs. (66.0+/-18.3)%, P<0.05] in the
      CFA-treated group than those in the NS-treated group respectively. CONCLUSION:
      CFA may inhibit beta cell apoptosis in NOD mice by regulating Fas, FasL and Bcl-x
      expression on cells within islets.

PMID- 17213579
TI  - [Porcine endogenous retrovirus in Daweizi pigs in Hunan].
AB  - OBJECTIVE: To detect porcine endogenous retrovirus (PERV) in Daweizi pigs and to
      provide basic parameters of evaluating the biological safety for
      xenotransplantation from pigs to humans. METHODS: Ear tissues from 42 individuals
      were randomly collected from a Daweizi pig population. PCR and RT-PCR were
      performed to detect PERV proviral DNA and mRNA respectively. Finally, env-A, env
      B, and env-C were amplified, sequenced, and analyzed using the BLAST software in
      National Center for Biotechnology Information. RESULTS: PERV proviral DNA and
      mRNA could be detected in the 42 individuals by PCR and RT-PCR, respectively. env
      A, env-B and env-C were detected in all the individuals. Compared with other pig
      species (AY288779, DQ011794 and AY534304), there was 1 and 8 bp differences in
      the sequences of env-A and env-C, while no difference in env-B. CONCLUSION: PERV
      exists and has transcriptive activity in Daweizi pigs. The predominate subtype is
      PERV-ABC. Env genes are firstly cloned and sequenced in Daweizi pigs and there
      are polymorphism in the breed. As to the biological safety, the breed was not
      suitable as a donor in xenotransplantation.

PMID- 17213580
TI  - [Effects of 5-azaC on methylation pattern of the perforin promoter of the
      perforin gene in normal human T cells].
AB  - OBJECTIVE: To investigate the effects of DNA hypomethylation on mRNA and protein
      expression of perforin promotor in T cells. METHODS: T cells were isolated from
      the peripheral venous blood of healthy donors by density gradient centrifugation.
      CD4(+) and CD8(+) subsets were isolated using Miltenyi beads and protocols
      provided by the manufacturer. Where indicated the T cells were stimulated with
      PHA for 24 h, then treated with 5-azaC for an additional 72 h. Genomic DNA, mRNA,
      and protein were isolated from untreated and 5-azaC-treated T cells. Purified DNA
      was treated with sodium bisulfite, the desired sequences were amplified in
      sequential fragments using nested PCR. The amplified fragments were cloned into
      bacteria DH5 alpha and 5 independent clones for each of the amplified fragments
      were sequenced. The expression of perforin was determined using real time RT-PCR
      and Western blot. RESULTS: The perforin mRNA and protein in the CD4(+) and CD8(+)
      subsets treated with 5-azaC were significantly higher than those in the untreated
      subsets (P<0.05). The results of bisulfite genomic sequencing showed that the
      methylation of perforin promotor was significantly reduced in the treated cells
      compared with the untreated cells (P<0.05). CONCLUSION: The mRNA and protein
      expression of perforin significantly increases in the CD4(+) and CD8(+) T cells
      treated with 5-azaC,which is associated with DNA hypomethylation of perforin
      promoter in T cells.

PMID- 17213581
TI  - [Expression of survivin mRNA of sputum and pleural effusions in human lung
      cancer].
AB  - OBJECTIVE: To determine the diagnostic value of the expression of survivin mRNA
      in sputum samples and pleural effusions in lung cancer. METHODS: The sputum
      samples of 104 patients with lung cancer and 30 patients with chronic obstructive
      pulmonary disease (COPD), and the pleural effusion of 56 patients with lung
      cancer and 30 patients with tuberculosis pleural effusions were detected.Reverse
      transcription-polymerase chain reaction (RT-PCR) was performed to detect the
      survivin mRNA expression in the specimens. The results were compared with their
      cytological examinations. RESULTS: The sensitivity of the cytological
      examinations combined with the detection of survivin mRNA in sputum samples was
      higher than that of either cytological examination or survivin mRNA detection of
      sputum samples alone (P<0.01). The sensitivity of the diagnosis for lung cancer
      increased from 37.5% (sputum cytology alone) to 78.8% (sputum survivin mRNA
      detection combined with sputum cytology) (P<0.01), and the negative predictive
      value increased from 31.6% (sputum cytology alone) to 43.5% (sputum survivin mRNA
      detection combined with sputum cytology) (P<0.01). The sensitivity of the
      cytological examinations combined with the detection of survivin mRNA in pleural
      effusion samples was higher than that of cytological examination of pleural
      effusion samples alone (P<0.01). The sensitivity of the diagnosis for lung cancer
      increased from 42.9% (pleural effusion cytology alone) to 80.4% (pleural effusion
      survivin mRNA detection combined with cytology) (P<0.01), and the negative
      predictive value increased from 48.4% (pleural effusion cytology alone) to 77.8%
      (pleural effusion survivin mRNA detection combined with cytology) (P<0.01).
      CONCLUSION: The detection of survivin mRNA from sputum samples and pleural
      effusions samples is a new diagnostic method for lung cancer.

PMID- 17213582
TI  - [Proliferation and differentiation-inducing effects of aminosteroid H42648 on
      K562 leukemia cells].
AB  - OBJECTIVE: To explore the proliferation and differentiation-inducing effects of
      aminosteroid H42648 on K562 leukemia cells. METHODS: The effects of H42648 on
      K562 cell proliferation were determined by cell count, colony count and MTT
      assay, and the differentiation by morphology, benzidine stain and flow cytometry.
      RESULTS: The growth of K562 cells was inhibited after the treatment with H42648
      for 5 days. The inhibition rates for K562 cells in MTT assay were (26.90+/-3.18)%
      and (43.26+/-2.54)% after the treatment by 10(-8)mol/L and 10(-6)mol/L H42648.
      The inhibitions for K562 cells in colony culture assay were (22.21+/-9.20)% and
      (48.71+/-8.24)% at 10(-8)mol/L and 10(-6)mol/L H42648, respectively. H42648 also
      induced K562 cells toward erythroid differentiation. It was verified by benzidine
      stain that the OD value at 10(-8)mol/L H42648 was increased by (153+/-17.65)%
      compared with the control, and at 10(-6)mol/L H42648 the OD value was increased
      by (250+/-4.60)% compared with the control. The morphology showed the
      differentiation tendency of K562 cells after the treatment. Data from flow
      cytometry showed that after the treatment with 10(-6)mol/L H42648 for 4 days,
      positive CD71 expression in differentiated K562 cells was 89.91%. CONCLUSION:
      H42648 can inhibit the proliferation of K562 cell lines and induce toward
      erythroid differentiation. H42648 may become a new lead for the differentiation
      inducing therapy for leukemia.

PMID- 17213583
TI  - [Inhibition of 1,3,8-trihydroxy-5-methoxyxanthone on cytochrome P450s].
AB  - OBJECTIVE: To explore the inhibitive effects of 1,3,8-trihydroxy-5
      methoxyxanthone (TMX) on cytochrome P450s (CYP450s) in human liver microsomes.
      METHODS: Probe drugs were incubated with and without adding TMX to determine the
      changes of enzyme activities. The concentration ratio of metabolites to probe
      drugs was used to present enzyme activities. Concentrations of the probe drugs
      and their metabolites in the incubated mixture were detected by high performance
      liquid chromatography. RESULTS: The variations (mean, 95%CI) of the activities of
      CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 x 10(-3) (2.03 x 10(-3),
      3.88 x 10(-3)), 3.14 x 10(-2) (1.87 x 10(-2), 4.42 x 10(-2)), 2.27 x 10(-3) (-1.4
      x 10(-2),1.81 x 10(-2)), 7.72 x 10(-2) (-0.83 x 10(-2), 0.2374), and -0.2548 (
      2.9802, 2.4707), respectively. The activities of CYP1A2 and CYP2C9 were
      significantly reduced in the present of TMX. CONCLUSION: TMX (10 micromol/L) has
      significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no
      significant inhibitive effect on the activities of CYP2C19, CYP2E1 and CYP3A4.

PMID- 17213584
TI  - [Concentration of IL-18 and PGE2 in synovial fluid in patients with
      osteoarthritis and its significance].
AB  - OBJECTIVE: To detect the concentrations of interleukin-18 (IL-18) and
      prostaglandin E2(PGE2) in synovial fluid (SF), and to determine the role of IL-18
      and PGE2 in osteoarthritis (OA) pathogenesis. METHODS: IL-18 and PGE2 were
      measured concurrently in synovial fluid samples from 54 patients with knee OA (OA
      group) and from 9 controls (control group). Quantitative determination of IL-18
      was performed by enzyme-linked immunosorbent assay (ELISA). PGE2 was examined by
      inhibitory enzyme-linked immunosorbent assay. A linear regression between IL-18
      and PGE2 was analysed. RESULTS: The concentrations of IL-18 and PGE2 in SF from
      the OA group were significantly higher than those from the control group
      (P<0.01). The average value of IL-18 in the control group was (28.768+/-13.575) x
      10(-9)ng/L, and (72.303+/-40.130) x 10(-9)ng/L in the OA group (P<0.01); the
      average value of PGE2 in the control group was (24.697+/-7.814) x 10(-9)ng/L, and
      (42.302+/-23.818) x 10(-9)ng/L in the OA group (P<0.01). IL-18 was related with
      PGE2 in a linear curve fashion (the control group: r=0.76, P<0.001; the OA group:
      r=0.94, P<0.001). CONCLUSION: IL-18 and PGE2 are significantly higher in the OA
      group than those in the control group, and they might take part in the cartilage
      degradation in OA pathogenesis. The increase of IL-18 might induce the increase
      of PGE2, and that might play an important role in OA pathogenesis.

PMID- 17213585
TI  - [In vitro study on the differentiation of bone marrow mesenchymal stem cells into
      epidermal stem cells].
AB  - OBJECTIVE: To explore the feasibility of the differentiation of bone marrow
      mesenchymal stem cells into epidermal stem cells. METHODS: Human bone mesenchymal
      stem cells (BMSCs) were isolated from the bone marrow of volunteers' ilium, and
      were purified and cultured in vitro and induced by supernatant liquid of HaCat
      cells. The morphologic changes of BMSCs were observed with electron microscope,
      and immunohistochemical examination was carried out to detect the positive
      staining of cytokeratin 10, cytokeratin 19 and integrin beta1 after one week
      induction. RESULTS: Large numbers of flat-polygon cells were closely connected
      and developed like road metal. The plenty threadlike keratins were observed in
      the cytoplasm. The immunohistochemical examination showed the positive staining
      of few cytokeratin 10, a great deal of cytokeratin 19 and integrin beta1 after
      the one week induction. CONCLUSION: Human BMSCs can differentiate into epidermal
      stem cells with supernatant liquid of HaCat cells and EGFs in vitro.

PMID- 17213586
TI  - [Suppression of MDR1 expression and restoration of sensitivity to chemotherapy in
      multidrug-resistant hepatocellular carcinoma cell line Bel7402/5-Fu by RNA
      interference].
AB  - OBJECTIVE: To investigate the suppression of MDR1 and P-glycoprotein induced by
      small interfering RNA and the restoration of sensitivity to chemotherapeutic
      drugs in multidrug-resistant hepatocellular carcinoma cell line Bel7402/5-Fu.
      METHODS: MDR1j targeted small interfering RNA duplexes were introduced into
      multidrug-resistant hepatocellular carcinoma cell line Bel7402/5-Fu. The
      suppression of MDR1 and its gene product P-glycoprotein was examined by RT-PCR
      and Western blot. MTT assay was performed to measure the reverse effect of small
      interfering RNA based on the results of IC50. Cell apoptosis was assessed by flow
      cytometry after various cell lines were treated with chemotherapeutic drugs.
      RESULTS: The overexpression of MDR1 and P-glycoprotein was suppressed efficiently
      by the introduction of small interfering RNA, which caused sequence-specific gene
      silence. The level of MDR1 in the transfected Bel7402/5-Fu cells reduced to
      22.55% and P-glycoprotein to 25.49% compared with those of the controls. The
      apoptosis rate of Bel7402/5-Fu cells increased significantly in the siRNA group
      during the chemotherapy (P<0.01). Their resistance to 5-Fu was reversed by 14.88
      folds, which indicated the restoration of sensitivity to drugs. CONCLUSION: Small
      interfering RNA can inhibit MDR1 expression effective and reverse the multidrug
      resistance mediated by P-glycoprotein.

PMID- 17213587
TI  - [Genetic polymorphisms and application of 9 STR loci of 5 ethnic groups in Gansu
      and Qinghai].
AB  - OBJECTIVE: To examine the genetic polymorphism of 9 STR loci in 5 ethnic groups
      (including Tu, Sala, Dongxiang, Baoan and Yugu) in Gansu and Qinghai, and to
      evaluate its application. METHODS: Nine STR loci (D3S1358, FGA, TH01, D7S820,
      VWA, CSF1PO, D5S818, D13S317 and TPOX) were selected as genetic markers. With STR
      compound amplification and genescan methods, in which STR loci were marked by
      fluorescence, the genotype of 5 ethnic groups were examined in 606 unrelated
      individuals by ABI 377 sequencer. These parameters, such as polymorphism
      information content (PIC), heterozygosity (H), discrimination power (DP) and
      probability of paternity exclusion (PPE) were calculated. RESULTS: The genotype
      frequencies of the 9 STR loci were in accordance with Hardy-Weinberg equilibrium.
      PIC was within 0.6054 - 0.8735, H was within 0.6158 - 0.8736, DP was within
      0.7964 - 0.9691, and PPE was within 0.4610 - 0.8838. Cluster analysis based on
      allele frequencies in genesis showed Tu, Sala, Dongxiang and Baoan ethnic groups
      were very close, but Yugu was a little bit far. There were obvious gene exchanges
      among the populations in north and south of China. CONCLUSION: All the 9 STR loci
      are highly polymorphic in the 5 ethnic groups, which can be useful genetic
      markers in forensic medicine and population genetics.

PMID- 17213588
TI  - [Effects of advanced glycation end products on the activity of NF-kappaB and the
      expression of fibronectin mRNA in the endothelial cells in aged rats].
AB  - OBJECTIVE: To explore the effects of advanced glycation end products (AGEs) on
      the activity of NF-kappaB and fibronectin (Fn) synthesis in the endothelial cells
      in aged rats. METHODS: Endothelial cells were cultured in M199 from the aorta of
      24 month old rats and divided into 3 groups: Group A (5 mmol/L glucose) as
      controls, Group B (25 mg/L AGEs for 48 h), and Group C (50 mg/L AGEs for 48 h).
      The activity of NF-kappaB was evaluated by immunofluorescence and the expression
      of Fn mRNA was measured by reverse transcription-polymerase chain reaction (RT
      PCR). RESULTS: Compared with the controls, AGEs induced the activity of NF-kappaB
      and increased the Fn mRNA expression in a concentration-dependent manner
      (P<0.05). CONCLUSION: The activity of NF-kappaB and up-regulated expression of Fn
      mRNA induced by AGEs may contribute to chronic complications of diabetes.

PMID- 17213589
TI  - [Clinical effects of the mixture of 5-fluorouracil and triamcinolone acetonide on
      capillary hemangioma of eyelid].
AB  - OBJECTIVE: To evaluate the clinical effects of the mixture of 5-fluorouracil (5
      FU) and triamcinolone acetonide on capillary hemangioma of eyelid. METHODS: One
      hundred and one patients with capillary hemangioma of eyelid were divided into
      Group A and Group B: Group A was injected with triamcinolone acetonide, and Group
      B was injected the mixture of 5-FU and triamcinolone acetonide. RESULTS: The cure
      rate was 68.3%, the total effective rate was 76.0%, and the average course of
      treatment was (8.1+/-3.4) months for Group A; the cure rate was 90.0%, the total
      effective rate was 96.6%, and the average course of treatment was (5.1+/-2.3)
      months for Group B. The therapeutic effect in Group B was better than that in
      Group A (P<0.05). The treatment period in Group B was shorter than that in Group
      A (P<0.05). CONCLUSION: 5-FU combining with triamcinolone acetonide has not only
      a better therapeutic effect, but also a shorter period of treatment.

PMID- 17213590
TI  - [Hepatitis C virus infection combined with systemic lupus erythematosus].
AB  - OBJECTIVE: To examine the hepatitis C virus (HCV) infection in systemic lupus
      erythematosus (SLE) patients, to investigate the influence of HCV infection, and
      to analyze the clinical appearances and experimental immunological characters of
      SLE. METHODS: Serum of 92 SLE patients and 58 normal control people was taken,
      and the HCV infection and experimental immunological characters were detected.
      SLE patients were divided into HCV infection group and non-HCV infection group
      according to the detective results. The immunological characters and clinical
      appearances were analyzed in the two groups. RESULTS: Thirteen of the 92 SLE
      patients were HCV positive, while only 2 of the 58 normal controls were positive.
      There were no significant differences in the clinical features including oral
      ulcer, arthritis, serositis, nephropathy, neural disorder, fever, as well as in
      the laboratory results including ANA, Anti-Ro/SSA, Anti-La/SSB, Anti-Sm, IgG and
      IgM in the two groups. HCV positive patients showed a lower frequency of
      butterfly erythema and positivity for Anti-dsDNA, and a higher frequency of
      cutaneous vasculitis, liver damage, positivity for RF and low C3, C4 levels.
      CONCLUSION: Patients with SLE showed a high prevalence of HCV infection, and HCV
      may cause some clinical and immunological changes in SLE.

PMID- 17213591
TI  - [Qualitative detection of hepatitis C virus core antigen in the serum in patients
      with chronic hepatitis C].
AB  - OBJECTIVE: To evaluate the clinical significance of serum hepatitis C virus (HCV)
      core antigen detected by enzyme linked immunosorbent assay (ELISA). METHODS: The
      serum HCV core antigen, which was taken from 149 patients with chronic hepatitis
      C, 20 patients of chronic hepatitis B and 20 health volunteers, was detected by
      ELISA. Meanwhile, the serum HCV RNA was detected by RT-PCR, and anti-HCV was
      detected by ELISA. RESULTS: The qualitative HCV core antigen in the serum, which
      was take from 20 patients of chronic hepatitis B and 20 health volunteers, was
      negative.The positive percentage of HCV core antigen was 49.66% in the 149 sera
      of patients with chronic hepatitis C. The coincidence of detective results of HCV
      RNA and HCV core antigen was 54.36%, without significant difference (P>0.05). The
      positive percentage of HCV RNA and HCV core antigen in the 149 anti-HCV antibody
      positive sera samples were 55.03% (82/149) and 49.66% (74/149), respectively, and
      there was no significant difference (P>0.05). CONCLUSION: The qualitative HCV
      core antigen detected by ELISA has a high specificity. The positive percentage of
      HCV core antigen in the serum of patients with chronic hepatitis C is 49.66%. HCV
      core antigen is related to HCV RNA. HCV core antigen may be a useful serum marker
      which could show HCV viraemia like HCV RNA.

PMID- 17213592
TI  - [Fetal posterior cranial fossa in the second and third trimester].
AB  - OBJECTIVE: To examine the normal range of the width of posterior cranial fossa
      (WPCF) in the second and third trimester by ultrasonography, and to investigate
      its relationship with fetal congenital and chromosome abnormality. METHODS: WPCF
      of 2484 fetus (gestational age from 14 to 41 weeks) was measured by
      ultrasonograph routinely, and the infants were followed up. RESULTS: In 2848
      fetus, 2772 were normal and 76 were abnormal. WPCF increased before 32 weeks,
      decreased after 33 weeks, the largest value of WPCF was 13.4 mm. The occurrence
      rate of WPCF> or =8 mm in normal fetus was 8.84%, and that in abnormal fetus was
      17.46%. Most fetuses with chromosome abnormality had normal WPCF in the second
      trimester, but some fetuses with remarkable broadening in the late stage. Some
      abnormal fetuses (such as water head, Dandy-Walker's syndrome etc) showed
      significant extension of WPCF. CONCLUSION: WPCF increases before 32 weeks,
      decreases after 33 weeks;and can be easily measured during 29 - 32 weeks. WPCF of
      some fetus with chromosome abnormality or with congenital abnormality is
      remarkably broadened in the late stage. The fetus of WPCF> or =10 mm should be
      followed up closely, and antenatal diagnosis should be done if WPCF is more than
      14 mm.

PMID- 17213593
TI  - [Myeloperoxidase in the plasma of patients with acute coronary syndrome].
AB  - OBJECTIVE: To determine the diagnostic value and efficacy for risk stratification
      of myeloperoxidase (MPO) levels in patients with acute coronary syndrome (ACS).
      METHODS: One hundred and sixty-two patients were enrolled in this study. All
      patients underwent coronary angiography. They were divided into 3 groups: ACS
      group (n=54), SAP group (n=54) and control group (n=54). Blood samples were taken
      from the artery before angiography in all patients and the concentrations of MPO,
      hsCRP and cTnI were measured. Each subject was asked details of history of
      hypertension, hyperlipidemia, diabetes and smoking habits. The efficacy of
      therapy, the cardiovascular events (myocardial infarction, the need for
      revascularization, or death) were recorded after 6 months of follow-up. RESULTS:
      The plasma MPO level in ACS group (30.98 ng/mL) was significantly higher than
      those in the SAP group (14.67 ng/mL) and the control group(14.23 ng/mL)(P<0.01),
      and the plasma MPO levels in patients of the SAP group and the control group were
      not significantly different (P=0.74). There was no obvious correlation between
      the levels of plasma MPO and the serum levels of cTnI, hsCRP,the prevalence of
      the 4 major risk factors for CHD. Multivariate logistic regression analysis
      showed that plasma MPO level, free plasma glucose and sex were the significant
      variables. The risk for subsequent cardiovascular events was higher in the
      patients with elevated level of MPO. CONCLUSION: Plasma MPO may be a new risk
      biomarker for ACS and may predict the incidence of subsequent cardiovascular
      events.

PMID- 17213594
TI  - [Pedicle screws in the posterior reconstructive operation of the lower cervical
      vertebra].
AB  - OBJECTIVE: To explore the efficiency of the cervical pedicle screws in the
      posterior reconstructive operation of the lower cervical diseases. METHODS: From
      November 2001 to July 2003, 31 patients suffering from the lower cervical
      diseases were treated with the posterior pedicle screws fixation. We put the
      screws in the inferior articular process of the upper centrum, the lateral of the
      intervertebral facet center (3 - 5 mm the medial edge of lateral mass). The
      angles of toe-in sagittal plane varied from 30 degrees to 45 degrees, and the
      screws were from 18 to 26 mm (22.3 mm) in average. RESULTS: There were 193
      pedicle screws in this group, and no one had spinal cord injury or vertebral
      artery injury. The improvement rate was 84.5%. Follow-up was from 9 to 28 months
      (17 months in average). The screws were fixed properly without being loose and
      broken, and the bone graft fusions within 9 to 12 months in the X-ray and CT scan
      examination were satisfactory. The Japanese orthopaedics association score (JOA)
      was 9.7 preoperatively, but it was raised to 16.3 postoperatively. CONCLUSION:
      The posterior reconstructive operation with cervical pedicle screws is a good
      choice for patients with lower cervical diseases.

PMID- 17213595
TI  - [Clinical observation of hand-assisted laparoscopic live donor nephrectomy].
AB  - OBJECTIVE: To investigate the feasibility and advantage of hand-assisted
      laparoscopic live donor nephrectomy in renal transplantation. METHODS: Six living
      relative donors received retroperitoneal left-side laparoscopic nephrectomy. The
      operating time of nephrectomy, the warm ischemic time, the recovery time of
      allograft and donors were recorded and analyzed. RESULTS: The mean operating time
      of nephrectomy was 150 minutes, the mean warm ischemic time was 3.5 minutes, and
      the mean time of micturition after graft reperfusion was 82 seconds. The donors
      recovered rapidly and returned to normal within 30 days . The urine volume and
      renal function of the 6 recipients were normal without complications in the
      following 3 months. CONCLUSION: Hand-assisted laparoscopic live donor nephrectomy
      is feasible with short operating time and warm ischemic time; the donors
      experience less pain, and recover rapidly. This technique may be widely used in
      living donor nephrectomy.

PMID- 17213596
TI  - [Effect of different doses of atorvastatin on adhesion molecules of the patients
      undergoing percutaneous coronary intervention].
AB  - OBJECTIVE: To determine the effect of different doses of atorvastatin on the
      serum soluble intercellular adhesion molecules-1 (sICAM-1) in patients undergoing
      percutaneous coronary intervention (PCI). METHODS: The study consisted of 38
      patients with unstable angina and 10 patients with old infarction who underwent
      elected PCI for stenotic lesions of the coronary artery. Patients were randomly
      assigned to either aggressive group or conventional one. After PCI the patients
      took atorvastatin 20 mg per day or 10 mg per day. Blood lipid profile was
      examined before, and 3 months after the PCI. SICAM-1 was examined before the PCI,
      48 hours and 3 months after the PCI. RESULTS: The total cholesterol and LDL
      Cholesterol 3 months after the PCI in the 2 groups were lower than those before
      the PCI (P<0.01). The aggressive group showed greater reduction in concentrations
      of TC and LDL-C than the conventional group (P<0.01). The changes in
      concentrations of HDL-C between pre-PCI and 3 months after the PCI and TG were
      not obvious (P>0.05). sICAM-1 in the 2 groups 48 hours after the PCI
      significantly higher than that before the PCI (P<0.01). But sICAM-1 in the 2
      groups 3 months after the PCI significantly lower than that before the PCI
      (P<0.01 or P<0.05). The aggressive group showed greater reduction than the
      conventional group (P<0.01). TC and LDL-C were positively correlated with sICAM
      1(r=0.2413, r=0.2691, all P<0.05). CONCLUSION: Atorvastatin 20 mg per day reduces
      TC, LDL-C, and sICAM-1 to a greater extent than atorvastatin 10 mg per day. The
      effect on sICAM-1 is partly related to reduce lipid profile.

PMID- 17213597
TI  - [Effects of intracoronary diltiazem on no-reflow phenomenon after emergent
      percutaneous coronary intervention in patients with acute myocardial infarction].
AB  - OBJECTIVE: To assess the effects of intracoronary diltiazem on no-reflow
      phenomenon of infarct-related artery (IRA) after emergent percutaneous
      transluminal coronary angioplasty or/and intracoronary stenting (PTCA/Stenting)
      in the patients with acute myocardial infarction (AMI). METHODS: We studied 34
      AMI patients with no-reflow phenomenon of IRA after emergent PTCA/Stenting
      between January 1999 and August 2005. Urokinase-treated group (n=16) was given
      intracoronary urokinase 30,0000 - 50,0000 units within 15 - 30 minutes between
      January 1999 and April 2002 while diltiazem-treated group (n=18) was given
      intracoronary diltiazem 0.5 - 2 mg within 10 - 30 minutes between May 2002 and
      August 2005. Fifteen minutes later, coronary arteriography (CAG) was performed
      and the thrombolysis in myocardial infarction (TIMI) flow grade was measured.
      RESULTS: No apparent change of TIMI flow grade was found between pre
      administration and post-administration of intracoronary urokinase, but TIMI flow
      grade was significantly improved after intracoronary diltiazem (P<0.01). TIMI
      flow grade of diltiazem-treated group was significantly higher than that of
      urokinase-treated group after the administration (P<0.05). The percentage of the
      patients who reached TIMI flow grade 3 after the intracoronary administration was
      higher in the diltiazem-treated group than that in the urokinase-treated group
      (P<0.01). CONCLUSION: The intracoronary administration of diltiazem 0.5~2mg can
      effectively improve the no-reflow phenomenon after emergent PTCA/Stenting in
      patients with AMI.

PMID- 17213598
TI  - [Spinal anesthesia with low dose sufentanil-bupivacaine in transurethral
      resection of the prostate].
AB  - OBJECTIVE: To explore the clinical efficacy of intrathecally administered low
      dose sufentanil-bupivacaine in transurethral resection of the prostate (TURP).
      METHODS. Ninety patient (ASA I - III) undergoing TURP were randomly divided into
      3 groups (n = 30); Group A, B and C. Group A received 7.5 mg bupivacaine + 5
      microg sufentanil + 10% glucose; Group B received 7.5 mg bupivacaine + 7.5 microg
      sufentanil + 10% glucose; Group C received 15 mg bupivacaine + 10% glucose. The
      volume was 3 mL in every group. SP, DP, HR, SpO2, the degree of motor and sensory
      blockade and the side effect were observed. RESULTS: SP/DP was significantly
      decreased in Group C than that in Group and Group B (p<0.05), HR and SpO2 in
      group B were decreased to different degrees 15 min after the injection (p<0.05).
      The complete recovery time of motor nerve blockade and the regression time of
      sensory blockade were obviously prolonged in Group C (p<0.05). There were no
      significant differences in analgesic effect among the three groups during the
      operation, but the incidence of pruritus was higher in both group A and Group B
      than that in Group C during the first 24 hours after the injection. CONCLUSION:
      Spinal anesthesia with low dose sufentanil-bupivacaine possesses relatively
      steady hemodynamics. The blockade degree of motor and sensory blockade in this
      spinal anesthesia is lower than that in standard spinal bupivacaine in TURP.

PMID- 17213599
TI  - [Bispectral index, cerebral state index and the predicted effect-site
      concentration at different clinical end-points during target-controlled infusion
      of propofol].
AB  - OBJECTIVE: To examine the predicted effect-site concentration of propofol at two
      clinical end-points: loss of verbal contact (LVC) and loss of consciousness
      (LOC), and to explore the relationship between bispectral index (BIS) values,
      cerebral state index (CSI) values and the predicted effect-site concentration
      during the target-controlled infusion of propofol. METHODS: In 20 patients during
      the target-controlled infusion of propofol, the propofol infusion was set at an
      initial effect-site concentration of 0.5 mg/L, and increased by 0.5 mg/L every 5
      min until 5 min after the modified observer's assessment of alertness/sedation
      scale (OAA/S) values reached zero. The predicted effect-site concentration of
      propofol, the values of CSI and BIS were recorded, and the sedation level was
      examined by the modified OAA/S every 20s. The predicted effect-site
      concentrations of propofol in target-controlled infusion (TCI) system were
      recorded when they increased by more than 0.1 mg/L. The predicted effect-site
      concentrations of propofol and the values of BIS and CSI at LVC and LOC in 5%,
      50% and 95% of the patients were calculated. RESULTS: There was good linearity
      between BIS and the predicted effect-site concentration of propofol (R(2)=0.787),
      as well as between CSI and the predicted effect-site concentration of propofol
      (R(2)=0.792). The predicted effect-site concentrations of propofol at LVC in 5%,
      50% and 95% of the patients were 1.1,1.8 and 2.4 mg/L, respectively. The values
      of BIS and CSI at LVC in 5%, 50% and 95% of the patients were 79.2, 69.2 and
      59.2; 74.9, 65.9 and 56.8, respectively. The predicted effect-site concentrations
      of propofol at LOC in 5%, 50% and 95% of the patients were 1.5, 2.5 and 3.4 mg/L,
      respectively. At LOC, the values of BIS and CSI in 5%, 50% and 95% of the patient
      were 73.6, 57.1 and 40.6; 65.2, 54.8 and 44.3, respectively. CONCLUSION: During
      target-controlled infusion of propofol, LVC and LOC occur within a definite range
      of predicted effect-site concentrations. There is the good linearity between BIS,
      CSI and the predicted effect-site concentrations of propofol. CSI may be more
      useful than BIS in predicting LVC and LOC.

PMID- 17213600
TI  - [Continuous veno-venous hemofiltration treatment for acute hypernatremia].
AB  - OBJECTIVE: To investigate the effect of continuous veno-venous hemofiltration
      (CVVHF) for acute hypernatremia. METHODS: Seven patients with hypernatremia were
      studied and treated with CVVHF. The serum sodium concentration and its remedy
      speed, creatinine, osmolarity, and blood pressure, etc were observed before and
      after CVVHF. RESULTS: The patients were treated with CVVHF averagely for 40
      hours. The serum sodium concentration, creatinine, osmolarity after the treatment
      decreased significantly and the APACHE II scores significantly improved. Among
      the 5 coma patients, 2 patients's consciousness was improved. CONCLUSION: CVVHF
      is effective and can be a new method for treating acute hypernatremia.

PMID- 17213601
TI  - [Apoptosis of psoriatic keratinocytes and the severity of patients' condition].
AB  - OBJECTIVE: To investigate the correlation between the apoptosis of psoriatic
      keratinocytes (KCs) in the psoriatic lesions and patient's condition. METHODS:
      Thirty patients with psoriasis were included. Activated caspase-3 was examined by
      colorimetric method in skin biopsy specimens. The apoptotic KCs were detected
      with terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling
      (TUNEL) assay in skin biopsy specimens. The severities of 26 patients with
      psoriasis vulgaris (PV) were assessed using the PASI scoring system and the
      severities of psoriatic lesions. RESULTS: Apoptotic indexes (AI) were higher in
      the pustular psoriatic lesions than those in the vulgaris psoriatic lesions
      (P<0.05). In 26 patients with PV, AI and activated caspase-3 in the lesions were
      significantly higher in the progressive stage than those in the static and the
      regressive stages (P<0.05). There were no correlations between PASI and AI or the
      expression of activated caspase-3 in PV lesions (P>0.05). The severities of
      psoriatic lesions were positively correlated to AI or the expression of activated
      caspase-3 in PV lesions (P<0.05). CONCLUSION: The amount of apoptotic KCs may be
      related to varied types, stages of psoriasis, and severities of psoriatic
      lesions.

PMID- 17213602
TI  - [Surgical treatment of cor triatriatum in 15 patients].
AB  - OBJECTIVE: To review the clinical data of pathological morphology, diagnosis,
      surgical treatment of cor triatriatum in 15 patients. METHODS: Fifteen patients
      with a mean age of (14.6+/-10.3) years (range from 6 months to 40 years) were
      performed operations under extracorporeal circulation. Fourteen of the patients
      had cor triatriatum sinister, and 1 had cor triatriatum dexter; 12 of the 15
      patients had other cardiac abnormalities. The excision of the fibromuscular
      membrane was accomplished through a right atrial incision in all of the 14 cases,
      and the associated abnormalities were corrected at the same time. RESULTS: One
      patient died after the operation, and the other survivors had good outcome.
      CONCLUSION: Operation is necessary if the diagnosis is clear. The patients
      generally have good prognosis. Surgical results of cor triatriatum depend on the
      complexity of associated defects and the adequacy of the repair.

PMID- 17213603
TI  - [Direct observation of the effect of mitral valvuloplasty on beating heart].
AB  - OBJECTIVE: To summarize the method and experience of direct observation of the
      effect of mitral valvuloplasty on beating heart. METHODS: Twelve patients with
      mitral regurgitation underwent mitral valvuloplasty. When the heart was beating
      slowly before releasing the aorta, the morphology and function of the mitral
      valve were evaluated by direct observation. If the results were unsatisfactory,
      further techniques were used to reach the goal. RESULTS: During the operation 2
      patients needed further techniques to make the mitral valve work well. No
      operative death and only 1 complication (low cardiac output syndrome) occurred.
      After 1 month follow-up later, mild regurgitation was found in 5 patients,
      moderate regurgitation in 1 and no obvious regurgitation in 6. CONCLUSION:
      Evaluating the effect of mitral valvuloplasty by direct observation on beating
      heart is practicable.

PMID- 17213604
TI  - [Clinical observation and follow-up of 186 cases of Kawasaki disease with lesion
      of coronary artery].
AB  - OBJECTIVE: To provide a reference for diagnosing and treating Kawasaki disease
      (KD). METHODS: We retrospectively analyzed the clinical data of 186 cases of
      final diagnosed Kawasaki disease and observed the characteristics of incomplete
      KD. RESULTS: There were 108 cases of KD with lesion of coronary artery in 186
      cases through 2-dimensional echocardiography. The incidence rate was 58.1%; it
      was easier to complicate with lesion of coronary artery in incomplete KD. Of
      them, slight coronary artery aneurysm was 60 cases (55.6%), midrange coronary
      artery aneurysm was 36 cases (33.3%), and severe coronary artery aneurysm was 12
      cases (11.1%). After 1 to 3 year's follow-up to all cases, the cases of slight
      coronary artery aneurysm all recovered in 6 months. The state of an illness in
      the cases of moderate and heavy coronary artery aneurysm was improved in 6 months
      except 3 huge aneurysm combining coronary artery thrombosis and coronary artery
      stenosis developed heart infarction and cardiomyopathy. The 30 cases of coronary
      artery aneurysm recovered in 1 year, 8 cases in 2 years, and 7 cases in 3 years.
      The patient that were not found with arterial coronary at the acute stage had no
      abnormality in 1 to 2 years after the treatment. CONCLUSION: It is easier to
      complicate with lesion of coronary artery in incomplete KD and the prognosis of
      coronary aneurysm is worse. To improve early diagnose and treatment of incomplete
      KD, it is necessary to use 2-dimensional echocardiography to check the suspected
      cases.

PMID- 17213605
TI  - [Effect of bee venom on adjuvant induced arthritis in rats].
AB  - OBJECTIVE: To investigate the anti-arthritic effect of bee venom in adjuvant
      induced arthritis (AIA) in rats. METHODS: Thirty-two male SD rats were enrolled
      in the experiment. Six were treated as negative controls and 20 AIA models were
      randomly divided into 3 groups: model controls (n=6), sodium chloride treatment
      group (n=6), and bee venom treatment group (n=8). The rats in the model control
      were killed before the treatment and the peripheral blood and synovium samples
      were collected for pre-treatment controls. The rats in the bee venom treatment
      group were injected hypodermically with bee venom for 14 days, while those in the
      sodium chloride treatment group were treated with the same volume of sodium
      chloride. During this period, the circumference of the affected joints and the
      total scores of the joints in all groups were measured every 2 days and X ray
      examinations were performed before and after the treatment. At the end of the
      treatment, all the rats were killed and their peripheral blood and synovium
      samples were collected for measurements of tumor necrosis factor TNF-alpha and
      interleukin IL-1 beta and histological studies, respectively. RESULTS: Compared
      with the sodium chloride group, the rats in the bee venom treatment group were
      less swollen in joints and circumference of joints and lower joint scores
      decreased (P<0.05). At the same time, the bone erosion and the infiltration of
      inflammatory cells in the synovium were also significantly reduced in the bee
      venom treatment group. In addition, the serum concentrations of TNF-alpha and IL
      1 beta were significantly lower in rats of the bee venom treatment group than
      those of the sodium chloride group (P<0.05 and P<0.01, respectively). CONCLUSION:
      Bee venom is effective in treating AIA by reducing synovitis, downregulating the
      serum concentrations of cytokine TNF-alpha and IL-1 beta and alleviating the bone
      erosion.

PMID- 17213606
TI  - [Trend of death cause of residents in Changde from 1973 to 2002].
AB  - OBJECTIVE: To discuss the cause of death for residents in Changde and guarantee
      the evidence for the health decision-making and control of diseases by the use of
      YPLL analysis and comprehensive evaluation on the dynamic cause of death of
      residents in Changde from 1973 to 2002. METHODS: The data is processed by the use
      of SPSS software package (version 11.0) and EXCEL software (version 2000) with
      the statistic methods of Cause Eliminated Life Table, Life Table, YPLL and etc.
      RESULTS: The average population reached 5384519 and the average gender proportion
      of male and female is 1.12 to 1 in Changed during 1973-2002. Since 1973, total
      population has risen from 483 to 596 at average annual rate of 7.89% while the
      birthrate has decreased from 53.78% in 1973 to 8.39% in 2002. The composition of
      population in Changde experienced great shift in the past 30 years. The
      proportion of children (0 - 14) in 2002 declined by 16.15% compared with that in
      1973 and the proportion of elder people has increased by 2.88% compared with that
      in 1973. The proportion of gender has ranged little by 1973-2002 although that of
      neonatal has ranged greatly. CONCLUSION: The total death number of Changde in
      2002 reached 1103233 and the mortality rate has sustained decline since 1973. The
      top 5 causes of death were diseases of respiratory system, circular system,
      damnification & poisoning, contagion & schistosomiasis, tumor and etc in 2002 and
      shifted a lot compared with that in 1973. The average life expectancy of
      residents in Changde was 67.6 from 1973 to 2002. The average life expectancy of
      males and females increased 12.63 and 11.93 years in 2002 compared with those in
      1972. In the past 30 years, the diseases of respiratory system has greatly
      influenced the life span of residents in Changde.

PMID- 17213607
TI  - [Treatment compliance and health needs of rural patients with peptic ulcer].
AB  - OBJECTIVE: To investigate the treatment compliance and basic health needs of
      rural patients with gastric ulcer. METHODS: One hundred and sixteen patients with
      gastric ulcer were measured with treatment compliance questionnaire. The
      questionnaire contained 3 aspects: chemical therapy, regular callback, and
      improvement in life style, and had another part of questions which were designed
      to investigate the basic health needs of the patients. RESULTS: The patient
      compliance rate in the aspect of improvement in life style was 4.3% (n=5). Both
      of the counterparts in the other 2 aspects were 7.8% (n=9). The main correlative
      factor with treatment compliance of the investigated patients was economic
      income. There were 105 patients (90.5%) needing health consultation, 98 patients
      (84.5%) needing diet instruction and 93 patients (80.2%) needing regular physical
      examination among the 116 patients investigated. CONCLUSION: The treatment
      compliance rate of rural patients with gastric ulcer was very low. It is
      necessary to emphasize health education.

PMID- 17213608
TI  - [Anesthetic strategies of foreign body in heart].

PMID- 17213609
TI  - [A case of superior sagittal sinus thrombosis].

PMID- 17213610
TI  - [A case of severe HIV occupational exposure and its treatment].

PMID- 17213611
TI  - [Clinical analysis of 170 cases head and neck lymphoma].
AB  - OBJECTIVE: To study the characteristics of head and neck lymphoma in order to
      improve its diagnose rate. METHODS: Review and analysis 170 patients with head
      and neck lymphoma in department of otolaryngology of Xiangya hospital from 1997
      to 2005. RESULTS: Nasal cavity and nasal sinuses, neck, tonsil were the common
      place of the origin of head and neck lymphoma. There are 9 cases Hodgkin disease
      and 161 cases non-Hodgkin lymphoma (NHL). T cellularity, B cellularity lymphoma,
      the mixed pattern and nullityping accounted for 60.9%, 36.0% and 3.1% of these
      patients with NHL, respectively. CHOP and radiotherapy were the main treatment
      method. CONCLUSION: The clinical and imageology manifestation of head and neck
      lymphoma were of diversification and no specificity, whose final diagnosis
      depended on immunohistochemistry.

PMID- 17213612
TI  - Diabetes/obesity-related inflammation, cardiac cell death and cardiomyopathy.
AB  - Pathogenesis of diabetic cardiomyopathy (DCM) is a complicate and chronic process
      that is secondary to acute cardiac responses to diabetes. One of the acute
      responses is cardiac cell death that plays a critical role in the initiation and
      development of DCM. Besides hyperglycemia, inflammatory response in the diabetic
      heart is also a major cause for cardiac cell death. Diabetes or obesity often
      causes systemic and cardiac increases in tumor necrosis factor-alpha, interleukin
      18 and plasminogen activator inhibitor-1. However, how these cytokines cause
      cardiac cell death remains unclear. It has been considered to relate to oxidative
      and/or nitrosative stress. We have demonstrated that metallothionein as a potent
      antioxidant or stress protein significantly protected the heart from oxidative
      damage and cell death caused by these cytokines, leading to effective prevention
      of DCM. The direct link of the inhibition of oxidative stress and damage to the
      prevention of cardiac cell death was defined by addition of superoxide or
      peroxynitrite specific inhibitor to completely prevent cytokine-induced cardiac
      cell death. Cardiac cell death is induced by the inflammatory cytokines that is
      increased in response to diabetes. Inflammatory cytokine-induced cardiac cell
      death is mediated by oxidative stress and is also the major initiator for DCM
      development.

PMID- 17213613
TI  - Stopped-in-loop flow analysis of trace vanadium in water.
AB  - The new concept of stopped-in-loop flow analysis (SIL-FA) is proposed, and an SIL
      FA method for the catalytic determination of vanadium is demonstrated. In an SIL
      format, a sample solution merges with reagent(s), and the well-mixed solution is
      loaded into a loop. The solution in the loop is separated by a six-way switching
      valve from the main stream. While the reaction proceeds in the stationary loop,
      the SIL-FA system does not need to establish a baseline continuously. This leads
      to a reduction in reagent consumption and waste generation compared with
      traditional flow injection analysis.

PMID- 17213615
TI  - The array biosensor: portable, automated systems.
AB  - With recent advances in surface chemistry, microfluidics, and data analysis,
      there are ever increasing reports of array-based methods for detecting and
      quantifying multiple targets. However, only a few systems have been described
      that require minimal preparation of complex samples and possess a means of
      quantitatively assessing matrix effects. The NRL Array Biosensor has been
      developed with the goal of rapid and sensitive detection of multiple targets from
      multiple samples analyzed simultaneously. A key characteristic of this system is
      its two-dimensional configuration, which allows controls and standards to be
      analyzed in parallel with unknowns. Although the majority of our work has focused
      on instrument automation and immunoassay development, we have recently initiated
      efforts to utilize alternative recognition molecules, such as peptides and
      sugars, for detection of a wider variety of targets. The array biosensor has
      demonstrated utility for a variety of applications, including food safety,
      disease diagnosis, monitoring immune response, and homeland security, and is
      presently being transitioned to the commercial sector for manufacturing.

PMID- 17213616
TI  - MPAI (mass probes aided ionization) method for total analysis of biomolecules by
      mass spectrometry.
AB  - We have designed and synthesized various mass probes, which enable us to
      effectively ionize various molecules to be detected with mass spectrometry. We
      call the ionization method using mass probes the "MPAI (mass probes aided
      ionization)" method. We aim at the sensitive detection of various biological
      molecules, and also the detection of bio-molecules by a single mass spectrometry
      serially without changing the mechanical settings. Here, we review mass probes
      for small molecules with various functional groups and mass probes for proteins.
      Further, we introduce newly developed mass probes for proteins for highly
      sensitive detection.

PMID- 17213617
TI  - Colorimetric biosensors based on DNA-nanoparticle conjugates.
AB  - In this review, we present an overview of the technologies in colorimetric
      biosensors based on DNA-nanoparticle conjugates. Two types of DNA-nanoparticles
      aggregation assays are summarized. One of the methods relies on cross-linking of
      the gold nanoparticle (GNP) by hybridization. The crosslinking system was used
      not only to detect target DNA sequences, but also to detect metal ions or small
      molecules which were recognized by DNAzymes. The other method is the GNP non
      crosslinking system. This approach shows high performance in the detection of
      single nucleotide polymorphisms. These methods do not need special equipment and
      open up a new possibility of point-of-care diagnoses.

PMID- 17213618
TI  - Quantum dots for single bio-molecule imaging.
AB  - The emerging nanomaterial, quantum dots or QDs, offers numerous potential
      applications in the biological area. As cell labeling probes, QDs become now an
      alternative of existing organic fluorescent dyes and fluorescent proteins. In
      this short review, we cover typical and successful applications of QDs as
      fluorescent probes in cell labeling and genomic diagnosis. As a future important
      application, biomolecular detection at a single molecule level utilizing QDs is
      also discussed.

PMID- 17213619
TI  - Methods for imaging and analyses of intracellular organelles using fluorescent
      and luminescent proteins.
AB  - One of the important features of eukaryotic cells is the presence of
      intracellular compartments, organelles. Each organelle plays an essential role in
      the organelle-specific function; each cooperates with others for maintaining the
      vital activity of living cells. To analyze the organelle-specific functions,
      researchers have used many fluorescent and luminescent reporter proteins
      extensively. The reporter proteins have provided unprecedented insights into the
      movement of proteins and their interactions in the organelles. In this review, we
      summarize recently validated methods for visualizing protein localization,
      dynamics and protein-protein interactions, and for identifying a series of
      proteins localized in organelles using newly developed reporter proteins.

PMID- 17213620
TI  - Surface plasmon resonance immunosensor for IgE analysis using two types of anti
      IgE antibodies with different active recognition sites.
AB  - A simple and novel method for the determination of an IgE antibody based on a
      surface plasmon resonance immunosensor for the diagnosis of an allergy is
      described. The method involves the use of an anti-IgE(D) antibody and an anti
      IgE(H) antibody, which reacts with the Ce2 domain and the Ce3 domain of the IgE
      antibody. The anti-IgE(D) antibody was immobilized on the gold surface of a
      sensor chip by physical adsorption. An IgE antibody sample was incubated by
      adding it to an anti-IgE(H) antibody solution to form an anti-IgE(H)
      immunocomplex through a reaction of the Ce3 domain of the IgE antibody. The
      incubated solution was introduced onto the sensor chip and the immunocomplex of
      the IgE-anti-IgE(H) then reacted with the anti-IgE(D) antibody immobilized on the
      sensor chip through the Ce2 domain of the IgE antibody part of the IgE-anti
      IgE(H) immunocomplex. The detection limit of the present method for the
      determination of the IgE antibody was about 10 ppb. The affinity constants for
      the anti-IgE(H) antibody immunocomplex with the IgE antibody in solution and that
      of the anti-IgE(H) antibody immunocomplex with the IgE antibody immobilized on
      the sensor chip by a biotin-streptavidin interaction were estimated to be 4.1 x
      10(7) M(-1) and 5.8 x 10(6) M(-1), respectively. The affinity constant for the
      immunocomplex of the anti-IgE(H) antibody with the IgE antibody with the anti
      IgE(D) immobilized on the sensor chip was estimated to be 4.9 x 10(7) M(-1), 20
      times larger than the affinity constant for the IgE antibody immunocomplex with
      the anti-IgE(D) antibody immobilized on the sensor chip, based on a direct
      immunoassay method of the IgE antibody under the same experimental conditions.

PMID- 17213621
TI  - Glucose oxidase-immobilized glass disks for imaging of D-glucose in acute brain
      slices.
AB  - A biotinylated glucose oxidase (bGOD)-immobilized glass disk was prepared for
      visualizing D-glucose fluxes in acute brain slices. A mouse hippocampal slice was
      placed on the bGOD disk and stimulated with a stimulant solution containing
      horseradish peroxidase (HRP) and a substrate DA-64, followed by capturing digital
      images of Bindschedler's Green (BG), an oxidized form of DA-64, with a CCD
      camera. The bGOD membranes responded proportionally to D-glucose, ranging from
      2.0 to 5.0 mM. Sucrose, GABA, L-glutamic acid, L-aspartic acid, glycine,
      acetylcholine and L-ascorbic acid at 10 mM did not cause any responses. The D
      glucose fluxes in mouse hippocampal slices stimulated by a hypoxia solution were
      neuronal region-dependent, i.e., dentate gyrus (DG), cornu ammonis 1 (CA1) and
      cornu ammonis 3 (CA3), while those stimulated by KCl was independent of the
      neuronal regions. The response of bGOD disks is discussed in terms of the
      principle, concentration dependence and selectivity.

PMID- 17213622
TI  - Enzyme-based field-effect transistor for adenosine triphosphate (ATP) sensing.
AB  - Adenosine triphosphate (ATP) not only functions as an energy-carrier substance
      and an informative molecule, but also acts as a marker substance in studies of
      both bio-traces and cellular/tissular viability. Due to the importance of the ATP
      function for living organisms, in situ assays of ATP are in demand in various
      fields, e.g., hygiene. In the present study, we developed an ATP sensor that
      combines the selective catalytic activity of enzyme and the properties of an ion
      selective field effect transistor (ISFET). In this system, the ATP hydrolyrase,
      "apyrase (EC 3.6.1.5.)" is encased in a gel and mounted on a Ta(2)O(5) ISFET gate
      surface. When the enzyme layer selectively catalyzes the dephosphorylation of
      ATP, protons are accumulated at the gate because the enzymatic reaction produces
      H(+) as a byproduct. Based on the interfacial enzymatic reaction, the response
      from the ISFET is completely dependent upon the ATP concentration in the bulk
      solution. This device is readily applicable to practical in situ ATP measurement,
      e.g. hygienic usage.

PMID- 17213623
TI  - 6-Chloro-N,N-diethyl-1,3,5-triazine-2,4-diamine (CAT) sensor based on biomimetic
      recognition utilizing a molecularly imprinted artificial receptor.
AB  - We aimed to develop a 6-chloro-N,N-diethyl-1,3,5-triazine-2,4-diamine (CAT)
      sensing system based on a biomimetic receptor of a molecularly imprinted polymer
      for CAT and electrochemical determination of CAT. A molecularly imprinted polymer
      for CAT was prepared by the polymerization of methacrylic acid (MAA) as a
      functional monomer and ethylene glycol dimethacrylate (EDMA) as a cross-linker
      with a template molecule (CAT) in dimethyl formamide (DMF). The polymer prepared
      with the ratio of these monomers (CAT:MAA:EDMA = 1:7.5:20) showed the most
      selective rebinding to CAT, and the obtained polymer was recognized as a CAT
      imprinted polymer (CAT-MIP). The effect of the specific imprinting sites of CAT
      MIP was demonstrated by Scatchard analysis. In an aqueous solution of CAT, CAT
      MIP showed the maximum binding of CAT in a 0.05 M phosphate buffer (PB), pH 5.0.
      The binding amount of CAT to CAT-MIP was 24% more than atrazine and 72% more than
      propazine. The CAT-sensing system was composed of a column of CAT-MIP particles
      and a voltammetry analyzer. The reductive current of CAT depended on the
      concentration of CAT up to 30 microM with the system.

PMID- 17213624
TI  - Construction of a dimethyl sulfoxide sensor based on dimethyl sulfoxide reductase
      immobilized on a au film electrode.
AB  - A novel dimethyl sulfoxide (DMSO) sensor using DMSO reductase and film electrodes
      was constructed. The Au and Ag electrodes were fabricated on slide glass by
      vacuum deposition and the application of a photolithographic technique. The micro
      chamber (4 x 50 x 1 mm, volume 200 microl) was fabricated on a
      poly(dimethylsiloxane) (PDMS) polymer. The Pt electrode was implanted in a PDMS
      polymer. DMSO reductase was immobilized on a Au film electrode with bovine serum
      albumin (BSA)-glutaraldehyde. This sensor could determine DMSO in an unpurged
      aqueous solution with glucose oxidase (GOD) and catalase (CAT) for oxygen
      removal. The DMSO sensor showed a linear response within 1 mM DMSO with a
      correlation coefficient of 0.999. The detection limit was 200 microM (3sigma),
      and the sensitivity was 23.8 mA M(-1) cm(-2). The relative standard deviations at
      each concentration were within 3.6%.

PMID- 17213625
TI  - Characterization of a glucose sensor prepared by electropolymerization of
      pyrroles containing a tris-bipyridine osmium complex.
AB  - A glucose sensor was developed by electrocopolymerization using pyrroles
      containing a tris-bipyridine (bpy) osmium complex (Os-py), pyrrole (py), pyrrole
      propanoic acid (PPA) and glucose oxidase (GOx) to improve the key performance
      characteristics, such as the sensitivity, selectivity, and long-term stability.
      Tris-bipyridine osmium pyrrole complexes with four different methylene moieties
      were utilized to correlate the methylene length with the glucose sensor
      performance. The electrocatalytic response of glucose was clearly observed at
      electrodes modified with Os-py, except for the electrode immobilized with the Os
      py complex containing the shortest methylene moiety. The current response to
      glucose increased up to a concentration of 100 mmol dm(-3). The electrocatalytic
      response to glucose at the [Os(bpy)(2)(py(6)-bpy)](2+/3+)/py/PPA/GOx electrode
      was stable for more than 100 days. Dissolved oxygen and potential interference
      compounds (ascorbic acid, uric acid, and acetaminophen) minimally perturbed the
      current response to glucose at the [Os(DM-bpy)(2)(py(6)-bpy)](2+/3+)/py/PPA/GOx
      electrode. Based on these results, a longer methylene moiety appears to improve
      the performance characteristics of a glucose sensor fabricated via the
      electropolymerization of tris-bipyridine osmium pyrrole complexes.

PMID- 17213626
TI  - Sensitive detection of estrogenic mycotoxin zearalenone by open sandwich
      immunoassay.
AB  - Zearalenone (ZEA) is an estrogenic mycotoxin produced by Fusarium sp., and its
      production on corn and small grains during storage has been of considerable
      concern. For sensitive ZEA detection, we applied an open sandwich (OS)
      immunoassay that can noncompetitively detect monovalent antigens utilizing an
      antigen-induced enhancement of the V(H)/V(L) interaction. We cloned the V(H) and
      V(L) cDNAs of anti-ZEA mAb to a split-Fv phagemid pKST2, and firstly both V(H)
      and V(L) fragments were displayed on M13 phage p9 and p7, respectively, using an
      amber suppressor, TG-1, as a host. The split-Fv phage showed specific binding to
      immobilized ZEA, which was well inhibited by free ZEA. Then, the V(H)/V(L)
      interaction and its antigen-dependency were analyzed using a non-suppressor
      HB2151 as a host to produce V(H)-displaying phage and his/myc-tagged soluble V(L)
      in the culture supernatant. By capturing V(L) with an anti-myc or -his antibody
      and probing bound V(H)-phage, ZEA was successfully detected with a superior
      detection limit as well as a wider working range than those of a competitive
      assay. Also, essentially the same results were reproduced with purified V(H)
      alkaline phosphatase and MBP-V(L) fusion proteins.

PMID- 17213627
TI  - Carbon felt-based bioelectrocatalytic flow detectors: highly sensitive
      amperometric determination of hydrogen peroxide using adsorbed peroxidase and
      thionine.
AB  - Horseradish peroxidase (HRP) and thionine (TN) were co-adsorbed onto a porous
      carbon felt (CF), and the resulting HRP and TN-adsorbed CF (HRP-TN-CF) was
      successfully used as a working electrode unit of a novel bioelectrocatalytic flow
      detector for a highly sensitive amperometric determination of hydrogen peroxide
      (H(2)O(2)). Co-adsorbed TN was essential to enhance the cathodic peak current of
      H(2)O(2), and the current responses of the HRP-TN-CF-based detector were much
      larger than those of the HRP-CF-based detector (without TN). When air-saturated
      0.1 M phosphate buffer (pH 7.0) was used as a carrier at a flow rate of 3.9
      ml/min, cathodic peak currents of H(2)O(2) (sample injection volume, 200 microl)
      obtained at an applied potential of 0 V (vs. Ag/AgCl) increased linearly up to 50
      microM with a detection limit of 0.1 microM. Repetitive 100 sample injection of
      100 microM H(2)O(2) induced no serious current decrease, and RSD was 0.41 to
      1.21% (n = 100). The HRP-TN-CF retained 42% of its original activity after 8 days
      of storage in 0.1 M phosphate buffer at 4 degrees C.

PMID- 17213628
TI  - DNA detection by an extended-gate FET sensor with a high-frequency voltage
      superimposed onto a reference electrode.
AB  - An extended-gate field-effect-transistor (FET) sensor with a gold-sensing
      electrode, to which a gold-thiol bond could easily be applied, was developed for
      DNA detection. Because the gold electrode is located in a different area from the
      FET, it can be operated without a light-shielding box by masking only the FET.
      However, when the FET sensor is used in an aqueous solution, fluctuation of the
      interface potential on the gold surface occurs, which results in decreased
      sensitivity. In DNA detection, 1 h or more was required to stabilize the drain
      current of the FET sensor after dipping it into the solution. To improve the
      sensitivity by reducing the fluctuation, we devised a measurement technique using
      a high-frequency voltage superimposed onto a reference electrode. With a
      superimposed high frequency voltage of over 1 kHz, the time required to stabilize
      the drain current of the FET sensor after dipping it in the solution was not only
      shortened to 5 min, but the fluctuation of the drain current was also reduced. As
      a result of applying this method, the FET sensor could successfully detect DNA
      hybridization and the extension reaction.

PMID- 17213629
TI  - Real-time detection of dopamine released from a nerve model cell by an enzyme
      catalyzed luminescence method and its application to drug assessment.
AB  - A real-time observation of neurotransmitter release from a nerve cell is a useful
      method for not only neuroscience research, but also assessing of the influence of
      chemicals, including drugs, on the human nervous system. In this study, a more
      simple and sensitive method for real-time monitoring of dopamine release from a
      nerve model cell was developed. Highly sensitive detection of dopamine was
      performed by using tyramine oxidase for dopamine oxidation, which was followed by
      a luminol luminescence reaction. This enzyme-catalyzed luminescence method was
      applied to observe dopamine release from the PC12 cell as a nerve model cell upon
      stimulation with acetylcholine and an acetylcholine receptor agonist. The results
      demonstrated that the real-time monitoring of the activation of the PC12 cell was
      easily performed by this method. This method possessed many advantages, such as
      high sensitivity, rapid measurement and no pretreatment for cells. It might be
      applied to drug screening and the assessment of harmful influences of food
      additives and pesticides on the nerves.

PMID- 17213630
TI  - Simple and selective sensing of cysteine using gold nanoparticles conjugated with
      a thermoresponsive copolymer having carboxyl groups.
AB  - We describe a simple, yet selective cysteine sensor based on gold nanoparticles
      (AuNPs) conjugated with thermoresponsive copolymers, the carboxyl groups of which
      are incorporated. Copolymer-conjugated AuNPs, used as the cysteine sensor, in a
      solution form sediment when cysteine is added. Heating followed by cooling the
      solution induces phase transitions of the thermoresponsive copolymers, resulting
      in an acceleration of sedimentation of the copolymer-conjugated AuNPs. The
      absorbance of supernatants at 520 nm, which are ascribed to a surface plasmon
      band of discrete AuNPs, decays with increasing concentration of cysteine.
      Sedimentation of the copolymer-conjugated AuNPs is specific to cysteine. The
      addition of other popular amino acids, or ascorbic acid, causes no sedimentation
      of the AuNPs. The relationship between the absorbance of the supernatant at 520
      nm and the cysteine concentration provides a sigmoidal profile at a concentration
      range between 1 x 10(-6) to 6 x 10(-6) mol dm(-3). The determination of cysteine
      in a supplement is achieved using an inflection point on the sigmoidal profiles.

PMID- 17213631
TI  - Development of a surface-reaction system in a nanoliter droplet made by an ink
      jet microchip.
AB  - A surface-reaction system in a nanoliter water pool using an ink-jet microchip
      was developed. The reaction system in the nanodroplets formed on a
      poly(dimethylsiloxane) (PDMS) coated glass slide increased the diffusion
      controlled reaction without using a nano-pump, specialized connector or highly
      sensitive detector. When nanoliter droplets were placed on the PDMS surface with
      a distance of 100 microm between them by the ink-jet microchip, the
      repeatabilities of the fluorescence intensity were 2.9% RSD (n = 7). The used ink
      jet microchip had 4 different injection ports, and the distance between the ports
      was 0.995 mm. It was necessary to correct the distance in order to mix or dilute
      samples in a small droplet. The correction was successfully performed by moving
      the X-Y stage using inhouse-made software. A linear relationship was obtained
      between the Resorufin concentrations and the fluorescence intensity. We applied
      this system to an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin A
      (IgA), and observed a difference in the fluorescence intensity derived from the
      amount of IgA (blank, 6.25 ng/mL, 12.5 ng/mL). These results show the usefulness
      of the open-type micro-analytical systems proposed by us.

PMID- 17213632
TI  - Galactose oxidase immobilized on silica in an analytical determination of
      galactose-containing carbohydrates.
AB  - Galactose oxidase from Fusarium graminearum IMV-1060 adsorbed on, and covalently
      bound to, silica carriers has been used for analytical determinations of D
      galactose and galactose-containing sugars. Using a flowing oxygen electrode of
      the Clark-type, sensor system for enzymatic analysis of water solutions of
      galactose-containing carbohydrates was made. Measurements were taken both in the
      pulse and continuous modes of a substrate flowing through a column with an
      immobilized biocatalyst. The linear measurement ranges for galactose-containing
      carbohydrates concentrations were determined.

PMID- 17213633
TI  - Application of a micro multiphase laminar flow on a microchip for extraction and
      determination of derivatized carbamate pesticides.
AB  - Determination of carbamate pesticides such as carbaryl, carbofuran, propoxur and
      bendiocarb was demonstrated on a microchip with newly designed microchannels
      developed for efficient solvent extraction. The pesticides were hydrolyzed to
      corresponding naphthols, coupled with p-nitrobenzenediazonium fluoroborate
      reagent, and then extracted into 1-butanol as colored azo derivatives and
      detected with a thermal lens microscope. Optimum flow rates for the aqueous and
      organic phases were evaluated in the continuous-flow chemical process established
      in the microchip. The calibration lines showed good linearity in the range of
      concentrations of 0.03 - 3 ppm (10(-7) - 10(-5) M) and a mass detection limit
      down to a nanogram level was achieved that is at least two orders of magnitude
      lower than the LODs for conventional spectrophotometric methods. Azo derivatives
      of the pesticides were successfully separated and identified by micellar
      electrokinetic chromatography (MEKC) using a sample prepared on a bulk scale.

PMID- 17213634
TI  - Anion- and cation-exchange MicroHPLC utilizing poly(methacrylates)-coated
      monolithic silica capillary columns.
AB  - A novel method was developed for the preparation of highly efficient anion- and
      cation-exchange microHPLC columns using an on-column polymerization of
      methacrylates having amine or sulfonic acid functional groups onto monolithic
      silica capillary columns modified with 3-methacryloxypropyltriethoxysilane as the
      anchor groups. The chromatographic evaluation of the columns using nucleic acids,
      nucleotides, and inorganic anions as samples showed the characteristics of the
      ion-exchange-type stationary phases. These columns exhibited higher separation
      efficiency when compared with the conventional particle-packed columns. A
      capillary column for the simultaneous anion- and cation-exchange separation could
      be prepared by a step-by-step functionalization. The advantages of this column
      preparation will include: (1) no need of column packing; (2) no need of the
      preparation of silane reagents possessing anion- and cation-exchange
      functionalities; (3) the amount of immobilized polymer could be controlled by
      changing polymerization conditions. These columns should be suitable for the
      separation of biologically active compounds by the microHPLC modes.

PMID- 17213635
TI  - Direct modification of mRNA by ferrocenyl carbodiimide and its application to
      electrochemical detection of mRNA.
AB  - Ferrocenyl carbodiimide (1) could be used for the direct labeling of synthetic
      RNA and expressed mRNA in vitro with the electrochemically active ferrocene
      moieties. These RNAs modified by 1 could be detected electrochemically coupled
      with a DNA probe-immobilized electrode. After hybridization of 1.1 Kb mRNA
      modified by 1 with the DNA probe-immobilized electrode, the peak charge observed
      by an Osteryoung square wave voltammetry (SWV) measurement correlated well with
      the concentration of mRNA, having a detection limit at the sub nanogram level.

PMID- 17213636
TI  - Electromagnetophoretic force measurement of a single binding interaction between
      lectin and yeast cell surfaces.
AB  - A novel measurement method of the binding force between a micrometer-sized
      particle and a solid surface in an electrolyte solution has been established by
      using the electromagnetophoretic buoyancy on the particle. By this method, we
      investigated the binding force between a yeast cell surface and an
      oligosaccharide-binding protein, concanavalin A (Con A), fixed on a silica
      capillary wall. The force measurement was carried out up to 60 pN. In a lower
      surface concentration of Con A, yeast cells could be desorbed by a force less
      than 60 pN. However, in a higher surface concentration after treated by 1 mg ml(
      1) solution, yeast cells were adsorbed with a force stronger than 60 pN. In this
      case, the addition of 10 mg ml(-1) D-mannose solution to the medium reduced the
      binding force to less than 60 pN. The observed adsorption force of yeast cells
      ranged within 30 - 40 pN, regardless of the interfacial amount of Con A. This
      force was thought to be the single binding force between a mannose group of the
      cell surface and an active site of Con A. Moreover, the dissociation rate
      constant of the single binding of yeast cell and Con A complex was determined as
      4.6 x 10(-3) s(-1) and the increment of the binding distance at the transition
      state as 0.33 nm from the desorption kinetic experiments of yeast cell under the
      constant pulling conditions of 10, 20 and 30 pN. Such satisfactory results
      demonstrate the novel advantages of the present method.

PMID- 17213638
TI  - Protection of psbAII transcript from ribonuclease degradation in vitro by DnaK2
      and DnaJ2 chaperones of the cyanobacterium Synechococcus elongatus PCC 7942.
AB  - Three dnaK and four dnaJ genes have been identified in the genome of
      cyanobacterium Synechococcus elongatus PCC 7942. Our comprehensive analysis of
      yeast two-hybrid screening revealed a specific interaction among DnaK2, DnaJ2,
      and RNase E, an essential endoribonuclease. We examined the effects of DnaK2 and
      DnaJ2 on RNase E activity by monitoring the digestion of psbAII transcript in
      vitro. The addition of DnaK2 and DnaJ2 obviously inhibited RNase E activity in an
      ATP-dependent manner. These results suggest that DnaK2 and DnaJ2 are involved in
      RNA degradation through interaction with RNase E.

PMID- 17213639
TI  - Molecular cloning of functional genes for high growth-temperature and salt
      tolerance of the basidiomycete Fomitopsis pinicola isolated in a mangrove forest
      in Micronesia.
AB  - Several functional genes encoding putative proteins, heat shock protein 70,
      sphingosine phosphate lyase, and Na+/H+ antiporter, were cloned from the
      basidiomycete Fomitopsis pinicola, a wood-rotting fungus isolated in the tropical
      mangrove forest of Pohnpei Island of the Federated States of Micronesia. The
      deduced amino acid sequences of the obtained genes involved in heat shock
      resistance, lipid synthesis, and salt tolerance showed diverse similarities to
      other homologous proteins. Molecular phylogenetic trees of these proteins
      suggested that encoded proteins of the cloned genes of F. pinicola differed
      remarkably from other homologs in various organisms, even fungal proteins.
      Putative candidates for other genes related to several cellular metabolisms were
      also amplified, implying the possible existence of those genes in F. pinicola.
      This is the first report of possibly functional genes derived from a
      basidiomycetous mushroom growing in tropical islands such as Micronesia. The
      genes found in this study might play important roles in the cellular survival of
      the basidiomycete F. pinicola under severe environmental conditions.

PMID- 17213640
TI  - Purification and biochemical characterization of soluble methane monooxygenase
      hydroxylase from Methylosinus trichosporium IMV 3011.
AB  - Methane monooxygenase hydroxylase was purified by chromatography and
      characterized by electrophoresis and spectroscopy. The molecular mass of
      hydroxylase was 201.3 KDa as determined by gel filtration, whereas the total
      molecular mass was 234 KDa as judged by SDS-PAGE. Structure study indicated that
      the enzyme is a homodimer structure, consisting of three subunits, designated
      alpha, beta, and gamma, with molecular masses of 58 KDa, 36 KDa, and 23 KDa
      respectively. IEF analysis indicated that the enzyme has a pI of 5.2. The UV-Vis
      spectrum of hydroxylase revealed an absorption peak near 281 nm and a weak
      shoulder peak around 395 nm-420 nm, and a fluorescence spectrum revealed an
      emission peak at 341.3 nm. Circular dichroism measurement indicated that
      hydroxylase mainly consists of alpha-helical regions. Finally, phylogenetic
      analysis indicated that this strain is very close to Methylosinus trichosporium
      OB3b.

PMID- 17213641
TI  - Distinctly different sensitivity in the induction and reversal of anergy of Th1
      and Th2 cells.
AB  - T cell anergy is one of the mechanisms of immunological tolerance. We examined in
      this study the distinct responses of Th1 and Th2 cells to in vitro anergic
      stimulation using Th1 and Th2 cells from two strains of T cell receptor
      transgenic mice. Proliferation of the Th2 cells was difficult to suppress by
      anergic stimulation, while that of Th1 cells was significantly inhibited even by
      weak stimulation. However, IL-4 production by Th2 cells was definitely reduced by
      anergic stimulation, although the inhibition level of IL-4 was lower than that of
      IFN-gamma production by Th1 cells. We also examined the reversal of anergy in
      both subsets. While both the anergized Th1 and Th2 cells responded to IL-2
      stimulation, only the anergy of the Th2 cells could be reversed. This result
      indicates that progression of the cell cycle was not sufficient for anergy
      reversal in Th1 cells. Our findings indicate that the induction and reversal of T
      cell anergy might be affected by the distinct signaling features of Th1 and Th2
      cells.

PMID- 17213642
TI  - Structure-activity relationship study of the bacterial actin-like protein MreB
      inhibitors: effects of substitution of benzyl group in S-benzylisothiourea.
AB  - We comprehensively investigated the effects of substitution of the benzyl group
      in S-benzylisothiourea derivatives on antibacterial activity, because we found
      previously that some substitutions enhanced it. A 2,4-Cl2-derivative was found to
      be the most effective compound, it was stronger than the original one in Gram
      negative rod shaped-bacteria such as Escherichia coli and Salmonella typhimurium.

PMID- 17213643
TI  - Effect of vitamin B12-enriched thraustochytrids on the population growth of
      rotifers.
AB  - Newly isolated thraustochytrids showed uptake of vitamin B12 from the culture
      into the cells. Cultivation of thraustochytrids in a medium containing 1
      microg/ml of vitamin B12 greatly increased the contents of vitamin B12 in the
      cells. Similarly to Schizochytrium limacinum, odd numbered fatty acids decreased
      in the cells of new isolates cultivated with vitamin B12. Vitamin B12-enriched
      thraustochytrids, strain mh0186, enhanced the population growth of rotifers fed
      on the cells as sole feed.

PMID- 17213644
TI  - Selective toxic effects of polyunsaturated fatty acids derived from Ulva fasciata
      on red tide phyotoplankter species.
AB  - Alpha-linolenic acid and linoleic acid isolated from Ulva fasciata showed toxic
      effects on red tide phytoplankters in a concentration-dependent manner. Among six
      species tested, raphidophycean flagellate Heterosigma akashiwo was the most
      susceptible to these fatty acids, and 50% lethal concentrations (LC50) of alpha
      linolenic acid and linoleic acid were estimated to be 0.58 and 1.91 microg/ml
      respectively, whereas dinoflagellate Gymnodinium impudicum and Heterocapsa
      circularisquama were highly resistant and no significant toxic effects were
      observed up to 1,000 microg/ml. Both fatty acids were less toxic to fish (devil
      stinger), zooplankters (brine shrimp and rotifer), and mammalian cell lines
      (U937, HeLa, Vero, and CHO cells) than H. akashiwo.

PMID- 17213645
TI  - Preparation of N-acylated proteins modified with fatty acids having a specific
      chain length using an insect cell-free protein synthesis system.
AB  - To establish a strategy to generate N-acylated proteins modified with fatty acids
      having a specific chain length, tGelsolin-streptag, an epitope-tagged model
      protein having an N-myristoylation motif, was synthesized using an insect cell
      free protein synthesis system in the presence of acyl-CoA with various fatty acid
      chain lengths. It was found that the fatty acid species attached to the N-termini
      fully depended on the acyl-CoA species added to the reaction mixture. N-Acylated
      proteins with fatty acid chain lengths of 8, 10, 12, and 14 were generated
      successfully.

PMID- 17213646
TI  - A role of a lymphocyte tryptase, granzyme A, in experimental ulcerative colitis.
AB  - In the large-intestinal mucosae of rats orally administered dextran sulfate
      sodium, which induces an enteritis resembling ulcerative colitis (UC), the
      activity for granzyme A, a lymphocyte tryptase, increased at an earlier stage
      than that at which UC markers (growth-regulated gene product/cytokine-induced
      neutrophil chemoattractant-1 and caspase-3) increased. This suggests involvement
      of the enzyme in the exacerbation and perpetuation of enteritis.

PMID- 17213647
TI  - Effect of royal jelly on bisphenol A-induced proliferation of human breast cancer
      cells.
AB  - Royal jelly is known as a functional food containing many useful minerals. In
      this study, we found an anti-environmental estrogen activity of royal jelly.
      Bisphenol A (BPA) is an environmental estrogen that stimulates proliferation of
      human breast cancer MCF-7 cells. Royal jelly inhibited the growth-promoting
      effect of BPA on MCF-7 cells, even though it did not affect the proliferation of
      cells in the absence of BPA. In addition, this inhibiting effect of royal jelly
      was heat-stable.

PMID- 17213648
TI  - Specific detection of soybean residues in processed foods by the polymerase chain
      reaction.
AB  - A sensitive qualitative detection method for soybeans in foods by using the
      polymerase chain reaction (PCR) was developed. For specific detection of soybeans
      with high specificity, the primer pair of Gym 81/Gym 82 was designed on the gene
      encoding the Glycine max repetitive sequence. The trace amount of soybeans in
      commercial food products could be qualitatively detected by this method.

PMID- 17213649
TI  - Efficient production of recombinant human (pro)renin utilizing a decahistidine
      tag attached at the C-terminus.
AB  - Human prorenin attached by a decahistidine tag at the C-terminus was produced in
      Chinese hamster ovary cells. The tagged protein secreted into the culture medium
      was in the inactive prorenin form, and was activated to mature renin by
      proteolytic removal of its prosegment by trypsin in the same manner as native
      prorenin. The tagged (pro)renin was efficiently purified by metal-chelate
      affinity chromatography. The enzymatic properties of mature renin carrying the
      tag were similar to native renin. These results indicate that the introduction of
      a decahistidine tag at the C-terminus does not interfere with either the correct
      folding of prorenin or the catalytic activity of mature renin.

PMID- 17213650
TI  - Induction of multiple cytokine secretion from RAW264.7 cells by alginate
      oligosaccharides.
AB  - We investigated the cytokine-inducing activities of guluronate (G3-G6) and
      mannuronate (M3-M6) oligomers on RAW264.7 cells with the Bio-Plex assay system.
      Relatively high levels of tumor necrosis factor-alpha (TNF-alpha), granulocyte
      colony-stimulating factor (G-CSF), monocyte chemoattractant protein-1 (MCP-1),
      regulated upon activation normal T cell expressed and secreted (RANTES),
      granulocyte macrophage (GM)-CSF, and eotaxin were induced by alginate oligomers
      to different extents depending on the oligomer structures, and low but
      significant levels of interleukin (IL)-1alpha, IL-1beta, IL-6, IL-9, and IL-13
      were also induced. Throughout all cytokines tested, M-oligomers tended to be more
      potent than G-oligomers in terms of cytokine induction, and this tendency was
      evident in differences between G3 and M3.

PMID- 17213651
TI  - Activation effects of Allium tuberosum Rottl. on choline acetyltransferase.
AB  - An ethanolic extract of Allium tuberosum Rottl. demonstrated potent choline
      acetytrasferase (ChAT) activating activity (45%) among 30 screened Korean edible
      plants. The ChAT activator of A. tuberoum Rottl. was purified and identified as
      ferulic acid [4-hydroxy-3-methoxycinnamic acid] via silica-gel open-column
      chromatography, HPLC, EI-MS, and 1H/13C-NMR. The ferulic acid from A. tuberoum
      Rottl. exhibited ChAT activity in a dose-dependent manner and showed notoxicity
      in a cell viability assay (MTT assay). We suggest that the ferulic acid from A.
      tuberoum Rottl. was the strong ChAT activator.

PMID- 17213652
TI  - Human MDR1 and MRP1 recognize berberine as their transport substrate.
AB  - To examine whether human ATP-binding cassette (ABC) transporters play a role in
      the detoxification of plant alkaloid berberine, we investigated berberine
      transport using multidrug resistance protein1 (MDR1) and multidrug resistance
      associated protein1 (MRP1). Cells expressing MDR1 or MRP1 accumulated less
      berberine. Berberine accumulation depended on the cellular ATP level, and was
      reversed by typical inhibitors of MDR1, suggesting that human MDR1 and MRP1
      directly efflux berberine as their substrate.

PMID- 17213653
TI  - Peculiar protein-protein interactions of the novel endoplasmic reticulum membrane
      protein Rcr1 and ubiquitin ligase Rsp5.
AB  - Overproduction of the ER membrane protein Rcr1 makes Saccharomyces cerevisiae
      resistant to Congo red by reducing the chitin content through a unknown
      mechanism. By both co-immunoprecipitation and yeast two-hybrid experiments,
      specific interaction between Rcr1 and the ubiquitin ligase Rsp5 was found. This
      binding was largely mediated by a singular VPEY sequence in Rcr1 in addition to
      PPSY, the consensus ligand motif of the WW domains. Mutant analysis indicated
      that Rsp5 and other Rcr1-interacting proteins discovered in the current screen
      were not engaged in Congo red resistance.

PMID- 17213654
TI  - Effects of Japanese Torreya (Torreya nucifera) seed oil on the activities and
      mRNA expression of lipid metabolism-related enzymes in rats.
AB  - The mechanism for the plasma and liver triacylglycerol-reducing effects of
      Japanese torreya (Torreya nucifera) seed oil containing sciadonic acid (all-cis
      5, 11, 14-eicosatrienoic acid) is reported. Male SD rats were fed experimental
      diets containing 10% torreya, corn, or soybean oil for 4 weeks, and the
      activities and mRNA expression of the enzymes involved in lipid metabolism were
      measured in the liver. The activities of some hepatic enzymes involved in fatty
      acid synthesis were lower in the rats fed torreya oil.

PMID- 17213655
TI  - Gene silencing by RNA interference in the koji mold Aspergillus oryzae.
AB  - We found the orthologous genes required for RNA interference (RNAi) in the
      Aspergillus oryzae genome database, and constructed a set of tools for gene
      silencing using RNAi in A. oryzae. This system utilizes compatible restriction
      enzyme sites so that only a single target gene fragment is required to create the
      hairpin RNA cassette. For ease of handling, we also separated the construction of
      the hairpin RNA cassette for the target gene from its subsequent introduction
      into the expression vector. Using the brlA gene as a target for RNAi, we detected
      decreased mRNA levels and a delayed conidiation phenotype in the transformants.
      Furthermore, even though A. oryzae possesses three copies of the alpha-amylase
      gene, a single copy of an alpha-amylase RNAi construct was sufficient to
      downregulate the mRNA levels and decrease the enzymatic activity to 10% of
      control levels. Gene silencing by RNAi should provide a powerful genetic tool for
      post-genomic studies of the industrially important fungus A. oryzae.

PMID- 17213656
TI  - Distribution of salivary Lactobacillus and Bifidobacterium species in periodontal
      health and disease.
AB  - We surveyed the distribution of salivary Lactobacillus and Bifidobacterium
      species in periodontitis patients and healthy subjects. Approximately 700
      lactobacilli and 300 bifidobacterial isolates were obtained from 16 young, orally
      healthy subjects (mean age +/- standard deviation: 21.0+/-2.0 y), 16
      periodontitis patients (51.6+/-13.8 y), and 14 well-maintained former
      periodontitis patients (60.2+/-9.6 y). Among eleven Lactobacillus species
      detected in saliva, L. salivarius, L. gasseri, and L. fermentum were prevalent,
      but no species was specifically associated with periodontal health. In contrast,
      of four Bifidobacterium species, B. adolescentis was specifically (P<0.05)
      prevalent in young healthy subjects compared with the other two groups.
      Furthermore, the bifidobacterial count of the well-maintained subjects was the
      highest (P<0.05) among the groups. These results suggest that bifidobacterial
      count and species might be associated with periodontal health status and/or age.

PMID- 17213657
TI  - Genetic and biochemical investigations on bacterial catabolic pathways for lignin
      derived aromatic compounds.
AB  - Lignins are the most abundant aromatic compounds in nature, and their
      decomposition is essential to the terrestrial carbon cycle. White rot fungi
      secreting phenol oxidases are assumed to be involved in the initial degradation
      of native lignin, whereas bacteria play a main role in the mineralization of
      lignin-derived low-molecular-weight compounds in soil. There are a number of
      reports on the degradation pathways for lignin-derived aromatic compounds, but
      their catabolism has not been enzymatically or genetically characterized.
      Sphingomonas paucimobilis SYK-6 is one of the best-characterized lignin-degrading
      bacteria. It can grow on a wide variety of lignin-related biaryls and monoaryls,
      including beta-aryl ether, biphenyl, diarylpropane, and phenylpropane. These
      compounds are degraded via the protocatechuate (PCA) 4,5-cleavage pathway or
      multiple 3-O-methylgallate (3MGA) catabolic pathways. In this review, the enzyme
      systems for beta-aryl ether and biphenyl degradation, O demethylation linked with
      one carbon metabolism, the PCA 4,5-cleavage pathway, and the multiple 3MGA
      catabolic pathways in SYK-6 are outlined.

PMID- 17213658
TI  - Dendritic cell-tumor fusion vaccine prevents tumor growth in vivo.
AB  - Dendritic cells (DCs) are potent antigen presenting cells that are uniquely
      effective in generating primary immune responses. DCs that are manipulated to
      present tumor antigens induce antitumor immunity in animal models and preclinical
      human studies. A myriad of strategies have been developed to load tumor antigen
      effectively onto DCs. DC-tumor fusion presents a spectrum of tumor-associated
      antigens to helper T- and cytotoxic T-cell populations in the context of DC
      mediated costimulatory signals. In this study, fusion cells (FCs) were generated
      with MCA-102 fibrosarcoma cells and murine bone marrow-derived myeloid DCs. The
      FCs coexpressed the DC-derived MHC class II and costimulatory molecules. The FCs
      also retained the functional properties of DCs and stimulated syngeneic T cell
      proliferation and interferon-gamma (IFN-gamma) production. Significantly, the
      results show that syngeneic T cells are primed by FCs to induce MHC class I
      dependent lysis of MCA-102 fibrosarcoma. These findings indicate that fusions of
      tumor cells and DCs activate T-cell responses against syngeneic tumors.

PMID- 17213659
TI  - Biodegradation of bisphenol A and related compounds by Sphingomonas sp. strain BP
      7 isolated from seawater.
AB  - A bacterium capable of assimilating 2,2-bis(4-hydroxyphenyl)propane (bisphenol
      A), strain BP-7, was isolated from offshore seawater samples on a medium
      containing bisphenol A as sole source of carbon and energy, and identified as
      Sphingomonas sp. strain BP-7. Other strains, Pseudomonas sp. strain BP-14,
      Pseudomonas sp. strain BP-15, and strain no. 24A, were also isolated from
      bisphenol A-enrichment culture of the seawater. These strains did not degrade
      bisphenol A, but accelerated the degradation of bisphenol A by Sphingomonas sp.
      strain BP-7. A mixed culture of Sphingomonas sp. strain BP-7 and Pseudomonas sp.
      strain BP-14 showed complete degradation of 100 ppm bisphenol A within 7 d in SSB
      YE medium, while Sphingomonas sp. strain BP-7 alone took about 40 d for complete
      consumption of bisphenol A accompanied by accumulation of 4-hydroxyacetophenone.
      On a nutritional supplementary medium, Sphingomonas sp. strain BP-7 completely
      degraded bisphenol A and 4-hydroxyacetophenone within 20 h. The strain degraded a
      variety of bisphenols, such as 1,1-bis(4-hydroxyphenyl)ethane, 2,2-bis(4-hydroxy
      3-methylphenyl)propane, 2,2-bis(4-hydroxyphenyl)butane, and 1,1-bis(4
      hydroxyphenyl)cyclohexane, and hydroxy aromatic compounds such as 4
      hydroxyacetophenone, 4-hydroxybenzoic acid, catechol, protocatechuic acid, and
      hydroquinone. The strain did not degrade bis(4-hydroxyphenyl)methane, bis(4
      hydroxyphenyl)sulfone, or bis(4-hydroxyphenyl)sulfide.

PMID- 17213660
TI  - Characterization of the sol operon in butanol-hyperproducing Clostridium
      saccharoperbutylacetonicum strain N1-4 and its degeneration mechanism.
AB  - The solventogenic sol operon consisting of bld, ctfA, ctfB, and adc was cloned
      from Clostridium saccharoperbutylacetonicum strain N1-4. These genes share as
      high as 95-98% similarity with the corresponding sol genes of Clostridium
      beijerinckii NCIMB 8052. The N1-4 sol gene cluster was transcribed in a
      polycistronic manner under the control of two promoters, and its transcription
      was highly induced during solventogenesis. Strain DGN3-4, the degenerated strain
      derived from N1-4, maintained the sol genes, but transcription of the DGN3-4 sol
      operon was hardly induced during solventogenesis. A substance extracted from the
      culture supernatants of wild-type N1-4 allowed us to induce transcription of the
      sol operon in DGN3-4. These results suggest that the degeneration is caused by
      the incompetence of the induction mechanism of the sol operon, and that
      transcription might be under the control of a quorum-sensing mechanism.

PMID- 17213661
TI  - Identification of a soluble NADPH oxidoreductase (BmNOX) with antiviral
      activities in the gut juice of Bombyx mori.
AB  - Silkworms show high variability in silk quality and disease resistance. Attempts
      are on to combine the disease tolerance of multivoltine races and the silk
      quality of bivoltine races to generate new races with desirable phenotypic
      traits. We report the identification of a 26.5-kDa protein that is overexpressed
      in the gut juice of disease-resistant multivoltine races and that has anti-BmNPV
      activity. We have characterized this protein as a soluble NADH-oxidoreductase
      like protein (BmNOX). Treatment of live BmNPV particles with BmNOX inhibited the
      capability of the viral particles to infect BmN cells in vitro.

PMID- 17213662
TI  - Antihypertensive and natriuretic effects of less-sodium soy sauce containing
      gamma-aminobutyric acid in spontaneously hypertensive rats.
AB  - We investigated the mechanism of the antihypertensive effect of less-sodium soy
      sauce containing gamma-aminobutyric acid (GABA) in spontaneously hypertensive
      rats (SHRs). When SHRs were given a diet with less-sodium soy sauce containing
      GABA (GABA-rich soy sauce group) for 6 weeks, the systolic blood pressure
      decreased as compared with that in rats fed diets with less-sodium soy sauce or a
      solution of salt. Renal sympathetic nerve activity (RSNA) and positive Na balance
      were reduced, and the urinary Na excretion tended to increase in the GABA-rich
      soy sauce group. Vascular hypertrophy of the thoracic aorta and the coronary and
      renal interlobular arteries tended to reduce in the GABA-rich soy sauce group.
      These results suggest that inhibition of Na retention by natriuresis, as a result
      of inhibition of RSNA by the GABA in the soy sauce contributed to the
      antihypertensive effect of GABA in the SHRs. Intake of less-sodium soy sauce
      containing GABA might help to reduce overall cardiovascular risk.

PMID- 17213663
TI  - Regulation of the phosphatidylinositol 3-kinase-Akt and the mitogen-activated
      protein kinase pathways by ursolic acid in human endometrial cancer cells.
AB  - The phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway and the mitogen
      activated protein kinase (MAPK) pathway are important in the development and
      proliferation of various human cancers. It has been found recently that ursolic
      acid treatment affects growth and apoptosis in cancer cells. We sought to
      determine whether prominent signaling pathways, including the PI3K-Akt pathway
      and the MAPK (JNK, P38, and P44/42) pathway mediate these effects. Endometrial
      cancer cells often have high levels of phosphorylated Akt seen in conjunction
      with a PTEN mutation or deletion. Elevation in Akt protects the cancer cell from
      apoptosis. Ursolic acid treatment moderately decreased PI3K levels in SNG-II
      cells. Treatment also decreased phospho-Akt and phospho-P44/42 in a dose- and
      time-dependent fashion, dramatically in SNG-II cells and moderately in HEC108
      cells. This effect was most pronounced following treatment with 50 mum ursolic
      acid for 72 h. Our study found inhibition of both the PI3K-Akt pathway and the
      MAPK pathway in two endometrial cancer cell lines, SNG-II and the poorly
      differentiated HEC108 cell line.

PMID- 17213664
TI  - Effect of various radical generators on insulin-dependent regulation of hepatic
      gene expression.
AB  - Oxidative stress is recognized to be associated with the development of insulin
      resistance. Although free radicals are generated in various ways in vivo, very
      few radical generators have been used to investigate the effect of oxidative
      stress on cellular insulin signaling. In order to compare the effect of radical
      generators with different sites and durations of radical formation on liver
      insulin action, primary cultured rat hepatocytes were incubated with radical
      generators and insulin-dependent regulation of gene expression was examined. The
      hydrophobic 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) radical and H2O2
      increased plasma membrane damage, and the hydrophilic 2-2'-azobis(2
      amidinopropane) dihydrochloride (AAPH) radical and buthionine sulfoxyimine (BSO)
      increased oxidation of intracellular substances. Paraquat (PQ) and H2O2 inhibited
      insulin-dependent repression of insulin-like growth factor-binding protein-1
      (IGFBP-1) and phosphoenolpyruvate carboxykinase (PEPCK) gene expression. These
      results indicate that PQ and H2O2 impair insulin action effectively and are
      suitable for examining crosstalk between oxidative stress and insulin signaling
      in liver-cell culture systems.

PMID- 17213665
TI  - Anti-hyperglycemic activity of an aqueous extract from flower buds of
      Cleistocalyx operculatus (Roxb.) Merr and Perry.
AB  - A screening of 5 plants used for making drinks in Vietnam revealed a Cleistocalyx
      operculatus (Roxb.) Merr and Perry flower bud extract to have the highest
      inhibitory activity against the alpha-glucosidase enzyme. The anti-hyperglycemic
      effects of an aqueous extract from flower buds of Cleistocalyx operculatus (CO),
      a commonly used material for drink preparation in Vietnam, were therefore
      investigated in vitro and in vivo. In vitro, the CO extract inhibited the rat
      intestinal maltase and sucrase activities, with IC50 values of 0.70 and 0.47
      mg/ml, respectively. These values are lower than those for a guava leaf extract
      (GE; IC50 0.97 and 1.28 mg/ml, respectively). Postprandial blood glucose testing
      of normal mice and STZ-induced diabetic rats by maltose loading (2 g/kg body
      weight (bw)) showed that the blood glucose reduction with CO (500 mg/kg bw) was
      slightly less than that with acarbose (25 mg/kg bw) but was more potent than that
      with GE (500 mg/kg bw). In an 8-week experiment, the blood glucose level of STZ
      diabetic rats treated with 500 mg of CO/kg bw/day was markedly decreased in
      comparison with that of non-treated diabetic rats. Consequently, CO is considered
      to be a promising material for preventing and treating diabetes.

PMID- 17213666
TI  - Effect of dietary oils on lymphocyte immunological activity in psychologically
      stressed mice.
AB  - Psychological stress has been shown to modulate immune functions. In this study,
      we investigated the effect of dietary oils (olive oil, soybean oil, and fish oil)
      on the social isolation stress-induced modulation of lymphocyte immunological
      activities in mice. In olive oil-fed, but not soybean oil- or fish oil-fed, mice,
      a 2-week isolation stress decreased the lymphocyte proliferative response,
      reduced the interferon-gamma and interleukin (IL)-10 secretions and increased the
      IL-4 secretion by lymphocytes. The isolation stress reduced the arachidonic acid
      content of lymphocytes markedly, moderately, and not at all in the olive oil-,
      soybean oil-, and fish oil-fed mice, respectively. In the olive oil-fed, but not
      soybean oil- or fish oil-fed, mice, the isolation stress up-regulated the
      expression level of mRNA for splenic heat-shock protein 70 and increased
      lymphocyte sensitivity to the antiproliferative effect of corticosterone. This is
      the first demonstration that effect of psychological stress on lymphocyte
      immunological activities can vary depending upon the dietary fatty acid
      composition.

PMID- 17213667
TI  - RNase E is required for induction of the glutamate-dependent acid resistance
      system in Escherichia coli.
AB  - The Escherichia coli RNase E is an essential endoribonuclease involved in
      processing and/or degradation of rRNAs, tRNAs, and non-coding small RNAs as well
      as many mRNAs. It is known that RNase E activity is somehow regulated by an RNA
      binding protein Hfq, at least in some cases. We searched for proteins that showed
      changes in expression in both hfq::cat and rne-1 mutant cells as compared with
      the wild type, and found that a protein band of 49-kDa decreased in these mutant
      cells at 42 degrees C, the restrictive temperature for rne-1. N-terminal amino
      acid sequencing identified it as a mixture of GadA and GadB, two isozymes of
      glutamate decarboxylase involved in glutamate-dependent acid resistance. The rne
      1 mutant as well as the hfq mutant showed decreased survival under acidic
      conditions (pH 2.5). Hfq is known to regulate the expression of GadA/B in RpoS-
      and GadY small RNA-dependent ways. We examined the expression of these two
      regulators in rne-1 mutant cells. In the mutant cells, the induction of GadY was
      defective at 42 degrees C, but the expression of RpoS was normal. These results
      indicate that RNase E is required for induction of the glutamate-dependent acid
      resistance system in a RpoS-independent manner.

PMID- 17213668
TI  - Suppression by licorice flavonoids of abdominal fat accumulation and body weight
      gain in high-fat diet-induced obese C57BL/6J mice.
AB  - We applied licorice flavonoid oil (LFO) to high-fat diet-induced obese C57BL/6J
      mice and investigated its effect. LFO contains hydrophobic flavonoids obtained
      from licorice by extraction with ethanol. The oil is a mixture of medium-chain
      triglycerides, having glabridin, a major flavonoid of licorice, concentrated to
      1.2% (w/w). Obese mice were fed on a high-fat diet containing LFO at 0 (control),
      0.5%, 1.0%, or 2.0% for 8 weeks. Compared with mice in the control group, those
      in the 1% and 2% LFO groups efficiently reduced the weight of abdominal white
      adipose tissues and body weight gain. A histological examination revealed that
      the adipocytes became smaller and the fatty degenerative state of the hepatocytes
      was improved in the 2% LFO group. A DNA microarray analysis of the liver showed
      up-regulation of those genes for beta-oxidation and down-regulation of those for
      fatty acid synthesis in the 2% LFO group. These findings suggest that LFO
      prevented and ameliorated diet-induced obesity via the regulation of lipid
      metabolism-related gene expression in the liver.

PMID- 17213669
TI  - Molecular cloning, expression, and characterization of a beta-agarase gene, agaD,
      from a marine bacterium, Vibrio sp. strain PO-303.
AB  - The beta-agarase-d gene (agaD) from a marine bacterium, Vibrio sp. strain PO-303,
      was cloned and expressed in Escherichia coli. The gene consists of 1,362 bp and
      encodes a protein of 453 amino acids with a predicted molecular weight of 50,824.
      The full length of agarase-d consists of a signal peptide, a glycoside hydrolase
      family 16 catalytic module (CM), and a carbohydrate binding module (CBM). The
      full length of agarase-d without the signal peptide (rAgaDDeltafull), the
      catalytic module (rAgaDCM), or the CBM (rAgaDCBM) was expressed in E. coli as
      recombinant proteins. rAgaDCM exhibited higher enzyme activity (63.6 units/mg)
      than rAgaDDeltafull (1.20 units/mg) against agarose. rAgaDCM hydrolyzed agar and
      porphyran to several oligosaccharides and acted on neoagarohexaose to produce
      neoagarotetraose and neoagarobiose, but did not act on neoagarotetraose. rAgaDCBM
      bound to agarose.

PMID- 17213670
TI  - Degradation of 2-nitrobenzoate by Burkholderia terrae strain KU-15.
AB  - Bacterial strain KU-15, identified as a Burkholderia terrae by 16S rRNA gene
      sequence analysis, was one of 11 new isolates that grew on 2-nitrobenzoate as
      sole source of carbon and nitrogen. Strain KU-15 was also found to grow on
      anthranilate, 4-nitrobenzoate, and 4-aminobenzoate. Whole cells of strain KU-15
      were found to accumulate ammonia in the medium, indicating that the degradation
      of 2-nitrobenzoate proceeds through a reductive route. Metabolite analyses by
      high-performance liquid chromatography indicated that 3-hydroxyanthranilate,
      anthranilate, and catechol are intermediates of 2-nitrobenzoate metabolism in
      strain KU-15. Enzyme studies suggested that 2-nitrobenzoate degradation occurs
      via the formation of 2-hydroxylaminobenzoate and that the pathway branches at
      this point to form two different aromatic intermediates: anthranilate and 3
      hydroxyanthranilate. PCR amplifications and DNA sequencing revealed DNA fragments
      encoding a polypeptide homologous to 2-amino-3-carboxymuconate 6-semialdehyde
      decarboxylase and anthranilate 1,2-dioxygenase.

PMID- 17213671
TI  - Molecular cloning of CYP76B9, a cytochrome P450 from Petunia hybrida, catalyzing
      the omega-hydroxylation of capric acid and lauric acid.
AB  - A cDNA encoding a cytochrome P450 (CYP76B9) was isolated from Petunia hybrida.
      Northern blot analysis revealed preferential expression of the gene in flowers
      and leaves. The recombinant yeast microsomes expressing CYP76B9 was allowed to
      react with capric acid and lauric acid as substrates. One major metabolite was
      produced from each fatty acid after incubation with yeast microsomes expressing
      CYP76B9. The metabolites were identified by gas chromatography-mass spectrometry
      (GC-MS) as omega-hydroxy capric acid and omega-hydroxy lauric acid. The kinetic
      parameters of the reactions were Km=9.4 microM and Vmax=13.6 mol min(-1) per mol
      of P450 for capric acid, and Km=5.7 microM and Vmax=19.1 mol min(-1) per mol of
      P450 for lauric acid. We found that the omega-hydroxy metabolites of capric acid
      and lauric acid can affect the plant growth of Arabidopsis thaliana. Plants grown
      in the presence of omega-hydroxy fatty acids exhibited shorter root length than
      control plants with the corresponding non-hydroxylated fatty acids.

PMID- 17213672
TI  - Genomic and cDNA cloning, characterization of Delonix regia trypsin inhibitor
      (DrTI) gene, and expression of DrTI in Escherichia coli.
AB  - Degenerate primers were designed based on all possible sequences of the N
      terminal and C-terminal regions of Delonix regia trypsin inhibitor (DrTI). Five
      hundred sixty-one bp of polymerase chain reaction (PCR) product was amplified
      using the above degenerate primers and genomic DNA and cDNA of Delonix regia as a
      template. The amplified PCR products were cloned and sequenced. DNA sequence
      analysis of cDNA and genomic clones of DrTI have the same nucleotide sequence in
      the coding region, and manifested a genomic clone without intervening sequences
      in the coding region. The amino acid sequence deduced from the DrTI genomic and
      cDNA clones agreed with that identified via amino acid sequencing analysis,
      except that two amino acid residues, Ser and Lys, existed between residues Lys141
      and Ser142. DrTI open reading frame was then amplified and cloned in-frame with
      GST in pGEX4T-1 and overexpressed in Escherichia coli to yield a glutathione S
      transferase (GST)-fusion protein with a calculated molecular mass of about 45
      kDa. The recombinant DrTI (reDrTI) was derived by treating the GST-DrTI fusion
      protein with thrombin. Both the reDrTI and GST-DrTI fusion protein exhibited a
      strong identical inhibitory effect on trypsin activity.

PMID- 17213673
TI  - 1,1-Diphenyl-2-picrylhydrazyl radical scavenging activity and tyrosinase
      inhibitory effects of constituents of sugarcane molasses.
AB  - In the course of our work into the use of cane by-products, we have studied the
      isolation and structural determination of bioactive compounds in sugarcane
      molasses. In this study, three stereo isomers of syringyl glycerol 3'-O-beta-D
      glucopyranoside, three stereo isomers of guaiacyl glycerol 3'-O-beta-D
      glucopyranoside, a syringyl glycerol 2'-O-beta-D-glucopyranoside, tachioside and
      a 2,3-dihydro-3,5-dihydroxy-6-methyl-4-(H)-pyran-4-one (DDMP) were isolated from
      the 25% methanol eluate by Amberlite XAD-2 column chromatography of sugarcane
      molasses. The structures of these compounds were determined on the basis of
      spectroscopic evidence. These isolated compounds were examined for their
      scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical species,
      and for their inhibitory activity against mushroom tyrosinase. All of the
      isolated compounds showed DPPH radical scavenging activity, while DDMP and
      tachioside showed mushroom tyrosinase inhibitory activity.

PMID- 17213674
TI  - Antihypertensive activities of a solid-state culture of Taiwanofungus camphoratus
      (Chang-chih) in spontaneously hypertensive rats.
AB  - Wild and solid-state cultures (SSC) of Taiwanofungus camphoratus (aka Antrodia
      camphorata and Chang-chih [CC]) were sequentially extracted with cold water,
      methanol, and hot water to get cold-water-soluble (CWS), methanol-soluble (MS),
      and hot-water-soluble (HWS) extracts, respectively. Only the MS extract exhibited
      angiotensin-converting enzyme (ACE) inhibitory activities. The antihypertensive
      effects of the MS extract (10 mg/kg BW) were measured in spontaneously
      hypertensive rats (SHR) and Wistar Kyoto (WKY) rats. MS extract of the SSC type
      was able to effectively lower the systolic blood pressure (SBP) and diastolic
      blood pressure (DBP) of SHR, but not of WKY rats, the results being significantly
      different from those for distilled water only (the blank). However, wild CC and
      its MS extract were not as effective as the SSC type in reducing SHR blood
      pressure and had no effect on WKY rats. SSC-type CC might be developed into a
      health food with the ability to regulate blood pressure.

PMID- 17213675
TI  - Cysteine supplementation decreases plasma homocysteine concentration in rats fed
      on a low-casein diet in rats.
AB  - The effect of dietary supplementation with cysteine on the plasma homocysteine
      concentration was investigated in rats fed on 10% casein (10C) and 30% casein
      (30C) diets. The 10C diet significantly increased the plasma homocysteine
      concentration as compared with the 30C diet. The hyperhomocysteinemia induced by
      the 10C diet was significantly suppressed by cysteine supplementation even at a
      0.3% level, whereas cysteine did not decrease the plasma homocysteine
      concentration when added to the 30C diet. In contrast, 0.3% methionine
      supplementation of the 10C diet tended to increase the plasma homocysteine
      concentration. Cysteine supplementation to rats fed on the 10C diet did not alter
      the plasma cysteine concentration and the hepatic activities of cystathionine
      beta-synthase and betaine:homocysteine S-methyltransferase, whereas it
      significantly decreased the hepatic concentrations of S-adenosylmethionine and
      betaine. These results suggest that cysteine supplementation might be effective
      for suppressing the hyperhomocysteinemia induced by a low-protein diet.

PMID- 17213676
TI  - Structural elucidation of 4-(cystein-S-yl)butyl glucosinolate from the leaves of
      Eruca sativa.
AB  - The structurally unique glucosinolate (GSL), 4-(cystein-S-yl)butyl GSL, was
      identified in the leaves of hydroponically-grown rocket salad (Eruca sativa
      Mill.). Its electrospray ionization mass spectrometry (ESI-MS)/MS spectrum
      indicated that this unusual GSL had a molecular weight of 414 as a desulfo (DS)
      GSL, and a molecular formula of C(14)H(25)N(2)O(8)S(2) based on its negative ion
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS) spectrum. For further confirmation, the 4-(cystein-S-yl)butyl DS
      GSL was prepared with authentic L-Ser and purified dimeric 4-mercaptobutyl DS
      GSL, and its chemical structure then confirmed by ESI-MS/MS data. It is named
      "glucorucolamine" as a trivial name from its ammonia sensitivity. This unique GSL
      was found to the greatest extent when rocket salad was grown in a 100% NH4+-N
      nutrient solution. Despite it clearly seems to reduce the detoxification of
      excess NH4+ in the leaves of rocket salad, present knowledge about the unique GSL
      is still far from being sufficient.

PMID- 17213677
TI  - Antithrombotic effects of odorless garlic powder both in vitro and in vivo.
AB  - Antithrombotic activities of odorless garlic powder were demonstrated in blood
      fibrinolytic and coagulation systems. Though the odorless garlic preparation did
      not influence tissue-type plasminogen activator (t-PA) or its inhibitor
      secretions from human umbilical vein endothelial cells, it enhanced plasmin
      generation by t-PA on fibrin film and in chromogenic assays by 1.8-fold and 8.7
      fold respectively. The coagulation system was considerably reduced after the
      administration of the garlic in a rat in situ loop model, indicating that
      increased levels of thrombin-antithrombin III (TAT) complex in the control group
      were significantly reduced to normal (sham) in the garlic group (p<0.05), which
      was associated with decreasing tendencies towards prolonged or increased values
      of coagulation parameters in the control group. These findings suggest that
      odorless garlic not only activates fibrinolytic activity by accelerating t-PA
      mediated plasminogen activation, but also suppresses the coagulation system by
      downregulating thrombin formation, suggesting a beneficial role in preventing
      pathological thrombus formation in such cardiovascular disorders.

PMID- 17213678
TI  - Effect of the arcA mutation on the expression of flagella genes in Escherichia
      coli.
AB  - Flagella expression in Escherichia coli is controlled in a hierarchical manner,
      in which class-1 gene products, FlhDC, functions as a master regulator to control
      class-2 genes that encode motility-related genes. fliA, one of the class 2 genes,
      encodes flagellum-specific sigma factor (FliA/Sigma F/Sigma-28), which is
      necessary for the expression of class-3 genes. Previously, we carried out
      transcriptome analyses of all two-component regulatory systems of E. coli, and
      determined that the arcA mutant showed the motility-defective phenotype. In this
      study, we characterized the arcA mutant, and we present evidence that ArcA is
      necessary for the expression of FliA, but not for the master regulators, FlhDC.
      The phosphorylation site of ArcA is necessary for motility, while a cognate
      histidine kinase, ArcB, appears not to be involved in motility. This suggests
      that there must be regulatory factors other than ArcB interacting with ArcA to
      control flagella genes.

PMID- 17213679
TI  - Gentisate 1,2-dioxygenase from Xanthobacter polyaromaticivorans 127W.
AB  - A putative gentisate 1,2-dioxygenase was encoded in the dibenzothiophene
      degradation gene cluster (dbd) from Xanthobacter polyaromaticivorans 127W. The
      deduced amino acid sequence showed high sequence similarity with gentisate
      dioxygenases from Pseudomonas alcaligenes (AAD49427, 65% identical),
      Bradyrhizobium japonicum (NP_766750, 64%), and P. aeruginosa (ZP_00135722, 54%),
      and moderate similarity with 1-hydroxy-2-naphthoate dioxygenase from Nocardioides
      sp. KP7 (BAA31235, 33%) and salicylate dioxygenase from Pseudaminobacter
      salicylatoxidans (AAQ91293, 33%). The enzyme, GDOxp, was heterologously produced
      in Escherichia coli and purified to homogeneity. GDOxp formed a tetramer and
      exhibited high dioxygenase activity against 1,4-dihydroxy 2-naphthoate as well as
      gentisate, suggesting unusually broad substrate specificity. GDOxp easily
      released ferrous ion under unfavorable temperature and pH conditions to become an
      inactive monomer protein. An inactive monomer protein can reconstitute a tetramer
      structure and restore enzyme activity in a cooperative manner upon the addition
      of ferrous ion. Chymotryptic digestion and protein truncation experiments
      suggested that the N-terminal region is important for the tetramerization of
      GDOxp.

PMID- 17213680
TI  - Transformation of the mycorrhizal basidiomycetes, Suillus grevillei and S.
      bovinus, by particle bombardment.
AB  - Mycorrhizal basidiomycetes, Suillus grevillei and S. bovinus, were transformed by
      particle bombardment. We isolated eight and four transformants from S. grevillei
      and S. bovinus respectively under three conditions differing in terms of target
      distance and helium pressure. The transformation frequencies were 1.2 and 0.6
      transformants/microg DNA. Plasmid DNAs were integrated into the genomic DNA of
      the transformants and stably maintained. This is the first description of the
      transformation of S. grevillei and S. bovinus by particle bombardment.

PMID- 17213681
TI  - Daily increase of fat ingestion mediated via mu-opioid receptor signaling
      pathway.
AB  - We investigated the involvement of opioid receptors such as the mu and delta
      receptors in the predominant elevation of corn oil appetite just after 5-day
      repeated treatment of corn oil ingestion. Rats were given 5% corn oil emulsified
      with 0.3% xanthan gum for 20 min at the same hour for 5 consecutive days. A
      strong appetite for fat was formed after the 5 days presentation, and it was
      inhibited by naloxonazine, a selective antagonist of the mu-1 receptor, at doses
      of 3 mg/kg, but not by antagonists of the opioid delta receptor. In days 6, after
      the formation of a strong appetite for corn oil, an additional injection of
      naloxonazine suppressed fat intake 0-30, 30-60, 60-90 and 90-150 min after the
      presentation of the corn oil, but antagonists of the opioid delta receptor did
      not. These data suggested that the opioid mu receptor is involved in the sharp
      elevation of corn oil appetite during repeated presentation of corn oil to rats.

PMID- 17213682
TI  - Functional characterization of Cl-/HCO3- exchange in villous cells of the mouse
      ileum.
AB  - At least three kinds of Cl(-)/HCO(3)(-) exchangers, SLC26A3, SLC26A6 and AE2,
      have been demonstrated to be expressed in the intestinal epithelial cell. To
      examine the functional expression of these exchangers in the native enterocyte,
      we studied the Cl(-)/HCO(3)(-)- exchange activity in isolated villi from the
      mouse ileum by microfluorometric intracellular pH (pH(i)) measurement. The pH(i)
      value increased upon Cl(-) removal when the villus was superfused with an HCO(3)(
      )/CO(2)-buffered solution, while the response was blunted when superfused with an
      HCO(3)(-)/CO(2)-free, Hepes-buffered solution. The recovery of pH(i) value
      induced by Cl(-) re-addition (after initial Cl(-) removal) was totally or
      partially mimicked by the addition of Br(-), I(-), F(-), NO(3)(-), or SO(4)(2-)
      (in the absence of Cl(-)). The increase in pH(i) value induced by Cl(-) removal
      was partially inhibited in the presence of DIDS (30 muM), tenidap (10 muM),
      niflumic acid (30 muM) or NPPB (30 muM). Increasing the K(+) concentration from 5
      mM to 60 mM in the superfusion solution induced a reversible increase in pH(i)
      value under the HCO(3)(-)/CO(2)-buffered condition, while it had hardly any
      effect on pH(i) under the Hepesbuffered condition. The K(+)-induced pH(i) changes
      were partially suppressed by removing Cl(-) from the superfusion solution. These
      results, together with the reported findings of mouse slc26a3, slc26a6 and AE2 in
      heterologously expressed systems, suggest the possibility that these three
      exchangers may all be functionally expressed in mouse ileal villous cells.

PMID- 17213683
TI  - Expression of cancer cachexia-related factors in human cancer xenografts: an
      immunohistochemical analysis.
AB  - We immunohistochemically evaluated the involvement of five cancer cachexia
      related factors, including leukemia-inhibitory factor (LIF), zinc-alpha2
      glycoprotein (ZAG), interleukin 6 (IL-6), proteolysis-inducing factor (PIF) and
      tumor necrosis factor alpha (TNF alpha) in causing cancer cachexia. Twenty-six
      xenografts implanted into mice were examined for the expression of the cancer
      cachexia-related factors, in relation to the body weight loss of the hosts. Five
      xenografts were categorized in the cachectic group, and the remaining 21
      xenografts belonged to the non-cachectic group. LIF was extensively expressed in
      both the cachectic and non-cachectic groups. ZAG and IL-6 were expressed in one
      of the cachectic and some non-cachectic xenografts. PIF and TNF alpha were
      detected in one and two non-cachectic xenografts, respectively, but in none of
      the cachectic ones. Any of five factors examined were not conclusive for causing
      cancer cachexia in the murine xenograft model. Further analysis is needed in
      order to elucidate the mechanisms responsible for cancer cachexia.

PMID- 17213684
TI  - Fluid resuscitation with hemoglobin-vesicle solution does not increase hypoxia or
      inflammatory responses in moderate hemorrhagic shock.
AB  - The aim of the present study was to compare the hypoxic and inflammatory effects
      of transfusing hemoglobin-vesicles (HbV) or lactated Ringer's (LR) solution on
      several organs in a hemorrhagic shock model. Hemorrhagic shock was induced in 48
      anesthetized rats by withdrawing 28 mL/kg blood. The animals were resuscitated by
      replacing the blood with an equal volume of HbV solution or three times the
      volume of LR solution. The heart, lung, liver, kidney and spleen were extracted
      at different time points following resuscitation, and mRNA expression levels of
      hypoxia-induced factor 1-alpha (HIF-1alpha) and tumor necrosis factor-alpha (TNF
      alpha) were determined. Blood lactate concentrations in the HbV group rapidly
      returned to baseline levels, whereas elevated lactate concentrations in the LR
      group were prolonged. There were no significant differences between the two
      resuscitation groups in terms of HIF-1alpha and TNF-alpha expression in the
      organs examined. HIF-1alpha and TNF-alpha expression in the lungs was
      significantly greater than in other organs. Our results suggest that
      resuscitation from hemorrhagic shock with HbV did not increase hypoxic or
      inflammatory effects in major organs, compared with resuscitation using LR
      solution, despite prolonged elevation of blood lactate.

PMID- 17213685
TI  - The function of connexin 43 on the differentiation of rat bone marrow cells in
      culture.
AB  - Connexin (Cx) 43-mediated gap-junctional intercellular communication (GJC) mainly
      regulates the osteoblastic differentiation, but much of the function of Cx43 on
      the differentiation of bone marrow cells is unclear. This study is aimed to
      clarify relationship between the differentiation of rat bone marrow cells and the
      function of Cx43. Bone marrow cells derived from four-week-old Wistar strain rats
      were grown in the presence and absence of 18-alpha-glycyrrhetinic acid (AGA, 100
      muM) to inhibit Cx43-mediated GJC. Expression of Cx43 gene and protein, and the
      level of intracellular cyclic adenosine monophosphate (cAMP) were determined as
      the assessment of the function in Cx43-mediated GJC, and alkaline phosphatase
      (ALP) activity and mineralization were measured as the assessment of osteoblastic
      differentiation. The Cx43 gene expression was first observed at 2 days, but under
      the condition in which rat bone marrow cells were treated with AGA, there was no
      significant effect on the Cx43 gene expression. By administrating AGA to rat bone
      marrow cells, all parameters of maturation but the Cx43 gene expression
      significantly decreased. The results of this experiment suggest that Cx43
      mediated GJC plays a critical role in rat bone marrow cells, progress toward
      maturation.

PMID- 17213686
TI  - The physiological and behavioral effects of subchronic intracisternal
      administration of TGF-beta in rats: comparison with the effects of CRF.
AB  - We studied the physiological and behavioral effects of subchronic intracisternal
      administration of transforming growth factor-beta (TGF-beta) for 7 days.
      Subchronic intracisternal administration of TGF-beta significantly inhibited the
      increase in body weight of rats but did not affect food intake. In the
      measurement of locomotor activity after the final intracisternal administration
      on day 7, the total count for 1.5 h increased significantly in the TGF-beta group
      compared with the vehicle group. However, that for 10 h was not different between
      both groups. Furthermore, significant elevations in oxygen consumption were
      observed in the TGF-beta group during both light and dark phase. Subchronic TGF
      beta treatment induced a significant decrease in the number of total leukocytes
      and lymphocytes and the relative weight of the thymus, and a significant increase
      in brown adipose tissue weight. Corticotropin-releasing factor (CRF) is the
      primary neuroendocrine factor released in response to stress. Subchronic
      treatment with CRF, as a positive control, significantly affected body weight,
      food intake, oxygen consumption, total leukocyte and lymphocyte counts, and
      thymus and adrenal weight. Subchronic TGF-beta administration partially mimicked
      the stress responses, implicating a role for TGF-beta in the brain in stress.

PMID- 17213687
TI  - Influence of long-term exposure to an air-conditioned environment on the diurnal
      cortisol rhythm.
AB  - In the present study, the influence of the long-term use of air-conditioning in
      summer on the cortisol rhythm was examined by measuring the rhythm in subjects
      who had been exposed to air-conditioning for a short [S] or long [L] time.
      Investigations were conducted twice in July and September. Atmospheric
      temperature and relative humidity near the subjects were measured for three days
      in each season. Saliva samples for cortisol analysis were collected every 2 hours
      during the daytime beginning at 8:00 h with subsequent sampling times at 10:00,
      12:00, 14:00, 16:00, 18:00, 20:00 and 22:00 h. A questionnaire on sleep and
      duration of air-conditioning use was also undertaken. Ambient mean temperature
      was higher in the S group (mean+/-SD; 30.8+/-1.2 degrees C in July, 28.0+/-0.8
      degrees C in September) than in the L group (28.0+/-1.2 degrees C in July, 27.3+/
      1.0 degrees C in September) (p<0.01), while mean relative humidity did not
      differ. There were no differences in bedtime, waking time and sleeping hours
      either between groups or months. Diurnal patterns of salivary cortisol rhythm in
      July and September were similar in the S group, but the L group had a delayed
      rise of morning cortisol secretion in September compared with July. These results
      suggest that long-term exposure to an air-conditioned environment might adversely
      affect the human cortisol rhythm.

PMID- 17213688
TI  - Combined physiological and anthropometrical databases as ergonomic tools.
AB  - The purpose of this study was to establish an ergonomic basis for the integration
      of female personnel at military workplaces. The results of anthropometrical and
      physiological measurements of 1337 male and female subjects (aged 18-25 years)
      are presented. The empirical design included classical and functional body
      measures of high ergonomic relevance. Additionally, the isometric forearm-flexor
      and knee-extensor forces of the subjects were tested as representative variables
      for their physiological suitability. With regard to biometric and strength
      parameters, the present results clearly show only small overlaps between the
      sexes. Rating the 5th percentile of the male subjects as an exclusion value, the
      anthropometrical variables (sitting and standing body height measures, shoulder
      breadth, hand length and breadth etc.) show that 29% up to 72% of the women do
      not match this criterion. The situation becomes even worse when strength
      parameters are taken into consideration: Only 26% (knee extensors) respectively
      3% (forearm flexors) of the females generate higher forces than the corresponding
      5th percentiles of their male counterparts. The application of the database
      established in this survey aims at the integration of female personnel at all
      kinds of military workplaces; our data account for a combination of
      anthropometrical and physiological variables. In contrast to former systems based
      on isolated percentile tables, the results of our investigation make multivariate
      queries possible in optimization processes. This type of combined database is to
      be considered a useful tool for the evaluation of workplaces and personal
      equipment, for general ergonomic considerations and for personnel planning
      purposes to prevent applicants from occupational harm.

PMID- 17213689
TI  - Obesity and cardiovascular risk factors among men and women aged 40 years and
      older in a rural area of Japan.
AB  - Obesity is one of the most common health problems, and is recognized worldwide as
      an "escalating epidemic." For the establishment of an obesity-prevention strategy
      in Japan, it is important to assess the association between obesity and
      cardiovascular risk factors. Therefore, we conducted anthropometric measures of
      obesity and investigated the association of obesity with cardiovascular risk
      factors such as hypertension, diabetes, and dyslipidemia among community-dwelling
      men (N=85) and women (N=173) aged 40 years and older. Height, weight, and waist
      circumference (WC) were measured, and body mass index (BMI) was calculated.
      Subjects with a BMI> or =25 kg/m(2) were considered obese (BMI obesity), while
      men with a WC> or =85 cm and women with a WC> or =90 cm were classified as obese
      (WC obesity). In the present study, we defined 'obesity' as a BMI> or =25 kg/m(2)
      or a WC> or =85 cm for men, and a BMI> or =25 kg/m(2) or a WC> or =90 cm for
      women. The results of an age- and sex-adjusted logistic regression analysis
      indicated that BMI obesity was associated with dyslipidemia (p=0.04), WC obesity
      was associated with dyslipidemia (p=0.07), and 'obesity' was associated with
      diabetes (p=0.06) and dyslipidemia (p=0.01). These results emphasize the
      importance of preventing obesity in Japan. Therefore, healthcare professionals
      should measure BMI and WC in order to enhance their assessment of cardiovascular
      risk.

PMID- 17213690
TI  - Survey on cellular phone usage on students in Thailand.
AB  - The number of cellular phone subscribers is increasing every year and there have
      been reports of health disorders related to the high-frequency radio waves. This
      paper considers the dependence of Thai university and high school students on
      cellular phones. A survey form (cellular phone dependence questionnaire: CPDQ)
      was distributed to 181 female and 177 male Thai university students and to 240
      female and 140 male Thai high school students. The surveys were collected,
      Cronbach alpha coefficient was calculated, and a factor analysis was performed
      using the principal factor method and varimax rotation. The total scores were
      16.54 to 20.04 and the Cronbach's alpha coefficients were 0.808 to 0.930.
      According to a factor analysis of 20 scored items, 4 factors were extracted for
      both male and female high school students, and the cumulative correlation
      coefficients of the male and female groups were 64.85% and 62.70%, respectively.
      Five factors were extracted for male university students and 6 factors were
      extracted for female university students, and the cumulative correlation
      coefficients were 58.08% and 57.91%, respectively. The W value results of the
      Shapiro-Wilk W-test for male university students, female university students,
      male high school students and female high school students were 0.969, 0.984,
      0.964, and 0.913 respectively, thus verifying the normality of the score
      distributions. The total scores for the Thai university students were higher than
      the scores for the Thai high school students. The factor analysis of female high
      school students confirmed a large difference compared to male university
      students, male high school students, and Japanese female university students.
      (The Japanese students were surveyed in an earlier study by Toda et al.). Also,
      the CPDQ total score was high, which indicated a strong tendency toward
      dependence.

PMID- 17213691
TI  - Involvement of anteroventral periventricular metastin/kisspeptin neurons in
      estrogen positive feedback action on luteinizing hormone release in female rats.
AB  - Metastin/kisspeptin, the KiSS-1 gene product, has been identified as an
      endogenous ligand of GPR54 that reportedly regulates GnRH/LH surges and estrous
      cyclicity in female rats. The aim of the present study was to determine if
      metastin/kisspeptin neurons are a target of estrogen positive feedback to induce
      GnRH/LH surges. We demonstrated that preoptic area (POA) infusion of the anti-rat
      metastin/kisspeptin monoclonal antibody blocked the estrogen-induced LH surge,
      indicating that endogenous metastin/kisspeptin released around the POA mediates
      the estrogen positive feedback effect on GnRH/LH release. Metastin/kisspeptin
      neurons in the anteroventral periventricular nucleus (AVPV) may be responsible
      for mediating the feedback effect because the percentage of c-Fos-expressing KiSS
      1 mRNA-positive cells to total KiSS-1 mRNA-positive cells was significantly
      higher in the afternoon than in the morning in the anteroventral periventricular
      nucleus (AVPV) of high estradiol (E(2))-treated females. The percentage of c-Fos
      expressing metastin/kisspeptin neurons was not different between the afternoon
      and morning in the arcuate nucleus (ARC). Most of the KiSS-1 mRNA expressing
      cells contain ERalpha immunoreactivity in the AVPV and ARC. In addition, AVPV
      KiSS-1 mRNA expressions were highest in the proestrous afternoon and lowest in
      the diestrus 1 in females and were increased by estrogen treatment in
      ovariectomized animals. On the other hand, the ARC KiSS-1 mRNA expressions were
      highest at diestrus 2 and lowest at proestrous afternoon and were increased by
      ovariectomy and decreased by high estrogen treatment. Males lacking the surge
      mode of GnRH/LH release showed no obvious cluster of metastin/kisspeptin
      immunoreactive neurons in the AVPV when compared with high E(2)-treated females,
      which showed a much greater density of these neurons. Taken together, the present
      study demonstrates that the AVPV metastin/kisspeptin neurons are a target of
      estrogen positive feedback to induce GnRH/LH surges in female rats.

PMID- 17213692
TI  - Carrier rate of Factor XI deficiency in stunted Japanese black cattle.
AB  - Blood examinations and genotyping of Factor XI (F11) were performed in growth
      retardation Japanese Black cattle and their dams. Genotyping of F11 revealed that
      the recessive homozygous and heterozygous genotype frequencies were 5.2% and
      50.0% in the Claudin-16 (CL-16) deficiency group (n=58), 0% and 14.2% in the
      renal dysplasia group (n=7), 0% and 26.1% in the non-CL-16 deficiency nephritis
      group (n=23), 8.9% and 46.7% in the hypogenesis syndrome group (n=45), 6.2% and
      25.0% in the neonatal weak calf syndrome group (n=32), 9.1% and 38.6% in the
      respective dams group (n=44), 0% and 23.1% in the normal cattle group (n=13), and
      5.9% and 38.2% in total (n=222), respectively. These results showed that the
      carrier rate of F11 deficiency was high in Japanese Black cattle, and that the CL
      16 deficiency, hypogenesis syndrome, neonatal weak calf syndrome, and dams groups
      had a large amount of recessive homozygous genotype than the other groups. No
      abnormal bleeding was observed clinically in the present study, and 4 of the
      recessive homozygous dams showed normal growth and parturition.

PMID- 17213693
TI  - Progression of the dose-related effects of estrogenic endocrine disruptors, an
      important factor in declining fertility, differs between the hypothalamo
      pituitary axis and reproductive organs of male mice.
AB  - For the purpose of investigation of working mechanisms in endocrine disruptors,
      we evaluated the dose-related effects of fetal and/or neonatal exposure to an
      estrogenic compound on the male reproductive organs in adult mice, particularly
      with respect to gene expression of steroidogenic acute regulatory protein (StAR).
      The pregnant ICR mice were given subcutaneous injections of 10 micro g/day/animal
      of diethylstilbestrol (DES) to subject the fetal mice to in utero exposure (IUE).
      Subsequently, the newborn male mice were subjected to neonatal exposure (NE) by
      treatment with vehicle or 0.1-10 micro g/day/animal of DES. Fertility rates of
      each group were as follows: control, 100%; IUE only, 60%; IUE+NE 0.1 micro g,
      25%; IUE+NE 1 micro g, 0%; IUE+NE 10 micro g, 0%. In general histology, germ cell
      layers in the seminiferous tubules were thinned in the group of IUE+NE 10 micro
      g. Hypoplasia of the Leydig cells, in which the staining intensity of eosin was
      diminished, was also observed in the groups of IUE+NE 0.1-10 micro g. The
      androgen receptor (AR) and estrogen receptor alpha (ERalpha) immunoexpression in
      the Leydig cells of IUE+NE 1-10 micro g was slightly lower than that in the
      controls. Long-term dysfunction of the hypothalamo-pituitary-testicular axis,
      including sustained hypoproduction of gonadotropin and testosterone, and altered
      expressions of steroid hormone receptors and StAR genes were observed. The
      hypothalamo-pituitary control of gonadotropin secretion may be affected by the
      smaller doses of estrogenic agents than the reproductive organs. Furthermore, the
      fertility rate in the male mice exposed to this estrogenic agent was closely
      correlated with the testosterone levels, and even more so with the rate-limiting
      factor of steroidogenesis, StAR. This finding suggests that endocrine disruptors
      have an important pronounced effect on StAR gene expression.

PMID- 17213694
TI  - Killing of feline T-lymphocytes by gamma-rays and energetic carbon ions.
AB  - High linear energy transfer (LET) heavy charged particles have previously been
      applied clinically to human cancer radiotherapy because of their excellent
      physical properties of selective dose distribution and higher relative biological
      effectiveness (RBE) for human; however, such an approach has yet to be applied to
      cat patients. The present study investigates the biological effectiveness of low
      LET gamma-rays (0.2 keV/micro m) compared to high-LET carbon ions (114 keV/micro
      m) in feline T- lymphocyte FeT-J cells. Clonogenic survival analysis revealed
      that the RBE value of carbon ions was 2.98 relative to a 10% survival dose
      (D(10)) by gamma-rays, and that the inactivation cross-section in cells exposed
      to gamma-rays and carbon ions was 0.023 and 38.9 micro m(2), respectively.
      Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end
      labeling (TUNEL) analysis revealed that TUNEL-positive frequency in carbon
      irradiation cells is higher than for gamma-irradiated cells against exposure to
      the same physical doses, but that very little difference in TUNEL-positive
      frequency is observed between cells exposed to the respective D(10) dose of gamma
      rays. Our data thus indicate that carbon ions are more effective for cell killing
      than gamma-rays at the same physical doses, but kill cells to an extent that is
      comparable to gamma-rays at the same biological doses. Carbon ion radiotherapy is
      therefore a promising modality for cat patients.

PMID- 17213695
TI  - C-reactive protein concentration in canine idiopathic polyarthritis.
AB  - To investigate the clinical utility of C-reactive protein (CRP) in idiopathic
      polyarthritis (IPA), its concentration was measured in dogs with IPA. The CRP
      concentration was markedly increased in all the IPA dogs at the time of diagnosis
      and decreased significantly in response to the initial corticosteroid treatment;
      this indicated that CRP can be used as an index for therapeutic response in IPA
      cases. Furthermore, at 6 months after the diagnosis, a significant association
      was observed between the CRP concentration at follow-up (6-13 days after the
      treatment was started) and the frequency of medication ("no or seldom-medicated
      (NSM)" groups or "continuing medication (CM)" groups). These results suggest that
      the initial response of CRP to corticosteroid treatment may be a prognostic
      factor of canine IPA.

PMID- 17213696
TI  - Development of a monoclonal antibody-based sandwich ELISA for detection of guinea
      pig interleukin-2.
AB  - Interleukin 2 (IL-2) is a T cell proliferation factor released by Th0- and Th1
      type helper T cells and is an essential cytokine for immune responses. In the
      present study, recombinant glutathione S-transferase (GST)-guinea pig IL-2 (GPIL
      2) fusion protein was prepared by Escherichia coli (E. coli) and by using this
      protein as an immunogen, monoclonal antibodies (mAbs) against GPIL-2 were
      produced to establish a basis for a research on immune responses in guinea pigs.
      Three stable hybridoma cell lines were established, and specific binding of each
      mAb to recombinant GPIL-2 produced by E. coli and insect cells infected with
      recombinant baculovirus was shown by enzyme linked immunosorbent assay (ELISA)
      and/or immunoblot analysis. Isotype analyses of these mAbs revealed that all
      three mAbs were IgG1 and had kappa chain. Furthermore, assessment of their
      epitopes by competition binding assay indicated that the mAbs obtained in this
      study bound to three different epitopes. Thus, a sandwich ELISA based on the two
      mAbs specific to different GPIL-2 epitopes was developed for detection of GPIL-2,
      which had a sensitivity threshold of about 0.3 ng/ml of GPIL-2.

PMID- 17213697
TI  - Characterization of Haemaphysalis longicornis recombinant cement-like antigens
      and preliminary study of their vaccination effects.
AB  - Two genes encoding immunodominant antigens, hlim2 and hlim3, were obtained from a
      salivary gland cDNA library of the hard tick, Haemaphysalis longicornis. The
      recombinant proteins were expressed in Escherichia coli as the GST fusion protein
      and used for immunization. We observed that the attachment rate of nymphal ticks
      fed on mice immunized with GST-hlim3 was significantly lower than that in the
      control group during the initial days of feeding. However, immunization with GST
      hlim3 did not affect the engorgement rate of the ticks. In sharp contrast, GST
      hlim2 did not influence the attachment rate and feeding period of ticks but had a
      significant reduction in the engorgement body weight. These data highlight the
      suitability of the 2 recombinant cement-like proteins for use in a cocktail
      vaccine.

PMID- 17213698
TI  - Persorption of luminal antigenic molecule and its specific antibody via apoptotic
      epithelial cells of intestinal villi and Peyer's patches into peripheral blood in
      rats.
AB  - The possibility of persorption of bovine serum albumin (BSA) molecules from
      mucous epithelial cells and its mechanism were investigated in rats orally pre
      immunized by BSA for 14 consecutive days. In the small and large intestines, both
      the BSA antigen (BSA-Ag) and its specific antibody (SpAb) were absorbed by the
      epithelial cells at the late apoptotic stage (ApoEp), and were subsequently
      transcytosed by membranes of the small vesicles. The basal cytoplasms containing
      highly-concentrated BSA-Ag and SpAb were occasionally fragmented into small
      cytoplasmic droplets that were secreted into the lamina propria. In Peyer's
      patches, both BSA-Ag and SpAb were more actively absorbed and transcytosed toward
      the dome area by the ApoEp of the dome apex than by the M cells. BSA-Ag and SpAb
      were finally persorbed into the portal blood and lymph, but were never secreted
      into the bile. They were also engulfed by macrophage-like cells in the villous
      lamina propria, mesenteric lymph node and spleen, and by hepatocytes in the
      liver. These findings suggest that sensitized soluble luminal antigens are taken
      up by ApoEp in the small intestine and are finally persorbed into the peripheral
      blood. The uptake of luminal antigen might be mediated by its luminal SpAb.

PMID- 17213699
TI  - Evaluation of right ventricular Tei index (index of myocardial performance) in
      healthy dogs and dogs with tricuspid regurgitation.
AB  - Right ventricular (RV) Tei index (index of myocardial performance) has been
      demonstrated to be clinically useful in estimating RV function in various human
      cardiac diseases. The purposes of this study were to validate the correlation
      between RV Tei index and RV function obtained by cardiac catheterization in
      healthy dogs, and to evaluate the RV Tei index in dogs with tricuspid
      regurgitation (TR). In healthy dogs, the RV Tei index significantly correlated
      with the RV peak +dP/dt (r=-0.80, p<0.0001) and -dP/dt (r=0.69, p=0.0001). In
      normal dogs, the RV Tei index was not significantly correlated with heart rate,
      body weight, and age. The RV Tei index significantly increased in dogs with
      moderate to severe TR (0.39 +/- 0.35, p=0.0015), filariasis (0.46 +/- 0.16,
      p=0.0131), and trivial to mild TR and severe mitral regurgitation (MR; 0.61 +/-
      0.14, p=0.0017) when compared with the normal dogs (0.17 +/- 0.10). In addition,
      the RV Tei index in dogs with TR significantly increased in association with
      pulmonary hypertension [PH(-), 0.19 +/- 0.09; PH(+), 0.65 +/- 0.14; respectively
      p<0.0001]. Our study has demonstrated that RV Tei index is a feasible approach to
      estimate RV function in dogs and is not influenced by heart rate, body weight,
      and aging. Further investigations are required to clarify the clinical
      significance of RV Tei index in dogs with right-sided cardiac diseases.

PMID- 17213700
TI  - Serological and virological surveys of reticuloendotheliosis in chickens in
      Taiwan.
AB  - Reticuloendotheliosis virus (REV) is widespread in the world. No related data has
      been reported in Taiwan. To determine the REV infection status, antibody
      determination and virus isolation were performed on chickens in Taiwan. The
      results revealed that serological flock prevalence for the REV antibody reached
      92.8% (39/42) amongst breeders (> 16 weeks old). Two different REV isolates were
      identified by reverse transcriptase-polymerase chain reaction, electron
      microscopic, immunofluorescent, and western blot assays after isolation. One of
      these viruses was isolated from a broiler breeder farm and the other was isolated
      from a Taiwan Country Chicken farm. Despite their different origins, the percent
      identity of the nucleotide sequences of the env gene of these two isolates was
      99.7%. These two strains were similar to the FPV-UI-REV strain, featuring 99.7%
      and 99.8% percent identity. Indeed, REV infection would appear to be quite common
      amongst chickens.

PMID- 17213701
TI  - Molecular typing by random amplification of polymorphic DNA (RAPD) and detection
      of virulence genes of Salmonella enterica subspecies enterica serovar Gallinarum
      biovar gallinarum.
AB  - Salmonella enterica subspecies enterica serovar Gallinarum biovar Gallinarum is
      the causative agent of fowl typhoid in chickens, outbreaks of which have
      devastated poultry populations in Korea since 1992. In order to identify genetic
      differences among S. Gallinarum isolates, bacteria were examined using the random
      amplified polymorphic DNA (RAPD) method. Of 13 arbitrary primers screened
      initially, the primer designated as universal rice primer-6 (URP-6) was selected
      for subsequent typing assays because it produced a distinctive and reproducible
      DNA fingerprint for a S. Gallinarum reference strain. URP-6-based RAPD analysis
      assigned 30 S. Gallinarum isolates into 6 types, with 26 isolates (86.6%)
      belonging to 2 major RAPD types. The distribution of virulence genes in S.
      Gallinarum isolates was examined by Southern hybridization. All tested isolates
      had the invasion gene, invA, the virulence plasmid gene, spvB, and the S.
      Enteritidis fimbrial gene, sefC. The distribution of virulence genes among S.
      Gallinarum isolates did not correlate with any specific RAPD type.

PMID- 17213702
TI  - Serodiagnostic comparison between two methods, ELISA and surface plasmon
      resonance for the detection of antibodies of classical swine fever.
AB  - A protein chip based on surface plasmon resonance (SPR) was developed to measure
      the antibody (Ab) titers of classical swine fever virus (CSFV) using the
      recombinant gp55 protein as an antigen. The diagnostic potential of this SPR
      assay for detecting the Ab titers to CSFV gp55 was compared that of the enzyme
      linked immunosorbent assay (ELISA) using 170 serum samples from 14 pig farms. The
      SPR assay was highly specific and sensitive, and there were no cross-reactions
      detected. There was a strong positive correlation between the SPR and ELISA
      titers (n=170, r=0.869, p<0.01). Therefore, the SPR label-free method is a
      valuable tool in the serodiagnosis of CSFV infection and determining Ab titers
      after vaccination.

PMID- 17213703
TI  - A case of feline pancreatitis.
AB  - A 14-year-old, spayed female, domestic shorthair cat was referred to us with
      anorexia, pyrexia, and jaundice. Total bilirubin (TBIL) and feline trypsin-like
      immunoreactivity (fTLI) levels were remarkably high. Based on laparoscopic biopsy
      of the pancreas, the cat was diagnosed as having pancreatitis. As a result of
      treatment with a synthetic protease inhibitor and corticosteroid, the TBIL and
      fTLI values returned to normal and the clinical course was good.

PMID- 17213704
TI  - Genetic diversity of benign Theileria parasites of cattle in the Okinawa
      Prefecture.
AB  - Benign Theileria parasites of cattle distributed in the Okinawa prefecture were
      characterized by allele-specific polymerase chain reaction (PCR) and DNA sequence
      analysis of the major piroplasm surface protein (MPSP) gene. Using universal or
      allele-specific primer sets, parasite DNA was amplified in 31 out of 48 blood
      samples obtained from beef cattle. Among the positive cases, mixed infections
      involving various combinations of I-, C-, and B-type parasites were detected in
      24 (77.4%) samples. Phylogenetic analysis based on the MPSP gene sequences
      revealed that parasites with the MPSP types 1-5 and 7, exist within the Okinawa
      prefecture.

PMID- 17213705
TI  - A case of glomus tumor in a dog.
AB  - A subcutaneous mass at the digit of the left-hind limb of a 12-year-old, male
      mongrel dog was examined. A white firm mass, approximately 1 x 2 cm in diameter,
      was excided surgically. Histopathologically, the mass formed multiple nodules
      consisting of mixed proliferation of round epithelioid cells arranged in cord or
      sheet-like structures and small spindle cells forming loose irregular bundles.
      The epithelioid cells often showed proliferation around the blood vessels. A few
      giant cells scattering in the neoplastic foci were observed. The neoplastic cells
      were positive for alpha-smooth muscle actin and vimentin, and were negative for
      cytokeratin (AE1/AE3), desmin, factor-VIII related antigen, S-100 protein, and
      neuron specific enolase. On the basis of these findings, this tumor was diagnosed
      as glomus tumor. Since the present neoplasm had neither recurrence nor distal
      metastasis during the 12 month after surgical resection, the biological natures
      of the present neoplasm are supposed to be benign.

PMID- 17213706
TI  - Establishment and biological characterization of canine histiocytic sarcoma cell
      lines.
AB  - Seven novel cell lines from canine histiocytic sarcoma (HS), three of which were
      disseminated cutaneous HS and four of which were synovial HS, were established.
      All of the established cell lines had the same morphological (by light and
      electron microscopic findings), cytochemical (alpha-naphthyl butyrate esterase
      positive), and immunohistochemical (vimentin- and lysozyme-positive, and cyto
      keratin-negative) characteristics as the original HS tumor cells. All of the
      established cell lines injected into nude mice subcutaneously produced solid
      tumors. Because the established cell lines also showed phagocytic and processing
      activities, the HS tumor cells appear to originate from the mononuclear
      phagocytic system cells, despite their differences in locations or organs.

PMID- 17213707
TI  - High level expression of biologically active canine interferon-alpha subtype 4
      using a baculovirus.
AB  - In this study, a high amount of bioactive recombinant canine interferon-alpha
      subtype 4 (CaIFN-alpha4) was expressed in a baculovirus system. For easy
      purification, it was expressed as a CaIFN-alpha4 bearing histidine hexamer at the
      C-terminal region, designated CaIFN-alpha4His. CaIFN-alpha4His was detected in
      culture supernatants of insect cells infected with the recombinant virus using
      sodium dodecyl sulfate-polyarcylamide gel electrophoresis (SDS-PAGE) and
      Coomassie Brilliant Blue staining. The level of expression was very high, and
      approximately 1 mg of purified protein, with 5.0 x 10(7) units/mg, was obtained
      from 300 ml of culture supernatant. The purified product showed antiviral
      activity against Vesicular stomatitis virus on canine tumor cell line A72 and
      chicken embryo fibroblast cells.

PMID- 17213708
TI  - Canine intestinal lactic acid bacteria agglutinated with concanavalin A.
AB  - Twenty-six out of 46 representative lactic acid bacteria (LAB) that we isolated
      from 36 dogs in a previous study were agglutinated by concanavalin A (ConA) at a
      concentration of 0.1563 mg/ml, while isolates did not agglutinate without the
      addition of ConA. Amongst the isolates, L. reuteri, L. mucosae, and E.
      canintestini agglutinated strongly, while L. gallinarum, L. kitasatonis, L.
      acidophilus, L. saerimneri, B. animalis ssp. animalis, P. acidilactici, and E.
      hirae did not agglutinate. ConA-agglutination of LAB was specifically inhibited
      by D-glucose, D-galactose, and D-mannose at a concentration of 1.563 mg/ml. Among
      the sugars, ConA-agglutination was strongly inhibited by D-mannose, while the
      inhibition level by D-glucose and D-galactose were lower than that of D-mannose.
      ConA- agglutination of all the LAB isolates was inhibited by D-mannose, except
      for L. reuteri (one species) and L. mucosae (two species). ConA-agglutination of
      Bifidobacterium spp. was inhibited by only D-mannose. Based on our results, ConA
      agglutination of LAB seems to be strain-specific, but not species-specific.

PMID- 17213709
TI  - Short term change of urinary N-acetyl-beta-D-glucosaminidase in reduced kidney
      mass with renal artery ligation.
AB  - The aim of the present study was to evaluate short term urinary NAG levels in a
      model of reduced kidney mass. The half and quarter kidney mass were made from
      ligation of the renal artery. Both groups decreased in the level of excreted NAG
      on day 1 and 2 after operation. On day 5 after operation, both groups achieved
      urinary enzyme levels comparable to that of the sham-operated group. The
      remaining compensated nephrons held normal range of excreted urinary NAG levels,
      although reduced number of nephrons resulted in a decline in urinary NAG levels.

PMID- 17213710
TI  - Bacteriological survey of mammary secretions from prepartum heifers in a dairy
      herd with a high prevalence of Staphylococcus aureus infection.
AB  - This study was performed to examine the bacteriological findings in 58 mammary
      secretions from 15 heifers at 4-5 weeks before parturition, and to evaluate
      whether a high prevalence of S. aureus infection in lactating cows affects the
      occurrence of S. aureus infection in prepartum heifers in the dairy herd. A total
      of 86.7%(13/15) of the heifers and 60.3%(35/58) of quarter milk samples from the
      heifers were bacteriologically positive. No S. aureus isolate was detected in
      mammary secretions from the heifers. Coagulase-negative staphylococcus (CNS)
      species were predominantly detected in 54.3%(19/35) and Streptococci other than
      Streptococcus agalactiae were isolated from 22.9%(8/35) of the quarters. A high
      S. aureus prevalence in the herd may not necessarily be a decisive factor for S.
      aureus infection in heifers.

PMID- 17213711
TI  - Immunohistolocalization of carbonic anhydrase isoenzymes (CA-I, -II and -III ) in
      canine epididymis.
AB  - The immunolocalization of the efferent duct and the epididymis in canine was
      firstly examined using an the immunohistochemical method with the canine carbonic
      anhydrase (CA) -I, CA-II and CA-III antisera. The efferent duct was
      immunonegative for all present canine CA antisera. However, some slender shaped
      epithelial cells in the head and body segments of the epididymal duct were
      intensely reacted to the CA-II antiserum. These results suggested that the CA-II
      might be controlled in the luminal environment in the head and body segments of
      the canine epididymis by the proton and bicarbonate balance for the maintenance
      of the spermatozoal stability and movement.

PMID- 17213712
TI  - A case of equine motor neuron disease (EMND).
AB  - We report a case of EMND in a heavy horse that was bred and trained in Hokkaido,
      Japan. Clinical symptoms included severe ataxia of all four limbs, tilted head,
      lethargy, and flaccid lips. Numerous axonal degenerations and swellings were
      observed in nuclei, mostly in the cerebellar dentate nucleus and the nucleus of
      the hypoglossal nerve, and in the ventral horn of the spinal cord. In the ventral
      horn of the spinal cord, neuronal degeneration, swelling, and/or necrosis were
      observed sporadically. The case was diagnosed as EMND from the clinical symptoms
      and pathological findings.

PMID- 17213713
TI  - Clinical usefulness of antibodies against Babesia gibsoni detected by ELISA with
      recombinant P50.
AB  - The clinical usefulness of antibodies against Babesia gibsoni detected by ELISA
      with recombinant P50 was examined in dogs in an area where B. gibsoni infection
      was endemic. Only 8 among 14 dogs with acute type B. gibsoni infection without a
      previous history of infection were positive. This high percentage of false
      negative results is thought to be a weak point of ELISA as a diagnostic tool.
      However, 14 other anemic dogs with a confirmed history of B. gibsoni infection
      were all positive, thus confirming the higher sensitivity of ELISA in detecting a
      history of infection.

PMID- 17213714
TI  - Ex vivo tissue discrimination by visible and near-infrared spectra with
      chemometrics.
AB  - The risk of infections from zoonotic pathogens of tissues and/or tissue-derived
      products has been increasing. One preventive approach in reducing infection risk
      is tissue decontamination, where selection and screening of highly infectious
      tissues are strictly followed. Therefore, the development of reliable analytical
      methods for rapid tissue discrimination is essentially important. In the present
      study, a procedure has been developed for intact tissue discrimination on the
      basis of multivariate analysis of visible and near-infrared (Vis-NIR) spectra of
      certain tissues such as brain, liver, kidney and testis of mice without any
      pretreatment. Transmittance spectra in the 600- to 1000-nm regions were subjected
      to a principal component analysis (PCA), and leave-out cross-validation was
      employed to develop multivariate models for tissue discrimination. The plot of
      PCA scores against Vis-NIR spectra of brains, kidneys, livers and testes from 11
      mice portrayed reliable tissue discrimination. This result suggests that Vis-NIR
      spectroscopy combined with chemometrics analysis may provide a potentially useful
      approach for rapid non-destructive discrimination of tissues.

PMID- 17213715
TI  - Seroprevalence of Mycobacterium avium subspecies paratuberculosis in Korean black
      goats (Capra hircus aegagrus).
AB  - In total, 582 sera from 116 black goat herds were analyzed by a commercially
      available ELISA kit to monitor the seroprevalence of Mycobacterium avium
      subspecies paratuberculosis (Mpt) in Korean black goats (Capra hircus aegagrus).
      The mean number of goats sampled per herd was 5.11, 4.66, and 5.38 for the
      northern, central, and southern regions of Korea, respectively. The apparent
      regional prevalence of Mpt was estimated at 18.2-38.2% and 4.6-15.3% for herds
      and goats, respectively. The Mpt-positive goats were predominantly detected in
      the south (n=28), compared to either the northern (n=9) or central (n=11) regions
      (chi=14.459, P<0.05). Our findings indicate that Mpt is prevalent among the goat
      population, but regional variation exists.

PMID- 17213716
TI  - Spinal nephroblastoma in a miniature Dachshund.
AB  - A 2-year-old castrated miniature Dachshund dog was presented to the Rakuno Gakuen
      Veterinary Teaching Hospital for diagnosis of progressive hindlimb paresis and
      ataxia. There was no thoracolumbar intervertebral disk hernia and magnetic
      resonance imaging revealed an intramedullary spinal cord lesion at the ninth and
      tenth thoracic vertebrae. Following surgical excision of the neoplasm, there was
      minor amelioration of neurological signs, but forelimb function was not
      recovered. The extracted tumor was histopathlogically diagnosed as spinal
      nephroblastoma.

PMID- 17213717
TI  - Spontaneous intracranial hypotension is associated with a risk of venous sinus
      thrombosis and subdural hematoma.

PMID- 17213718
TI  - Marcel Proust's lifelong tour of the Parisian Neurological Intelligentsia: from
      Brissaud and Dejerine to Sollier and Babinski.
AB  - In Search of Lost Time, the main novel of Marcel Proust (1871-1922) gives
      prominence to medicine, especially to neurology. Proust possessed excellent
      medical knowledge and maintained lifelong contact with neurologists. From 1881
      onward, he experienced recurrent attacks of asthma, a condition which, at the
      time, was considered belonging to 'neurasthenia'. Marcel's father, Adrien Proust,
      was a famous physician who had written papers on stroke, aphasia, hysteria and
      neurasthenia, and who introduced his son to Charcot's pupil, Edouard Brissaud,
      the founder of the Revue Neurologique. Three years later, Brissaud published a
      landmark book on asthma with a preface by Adrien Proust. In 1905, when Proust
      intended to undergo a 'cure' in order to improve his asthma and other symptoms,
      he first considered treatment by Jules Dejerine, who was to become Charcot's
      second successor. He also considered two Swiss physicians who had studied with
      Charcot and Vulpian: Henry Auguste Widmer, founder of the Clinique Valmont above
      Montreux, and Paul Dubois, a schoolmate of Dejerine, who practiced in Berne.
      Brissaud recommended Paul Sollier, under whose care Proust followed a 6-week
      'isolation cure'; Sollier, along with Babinski, was considered the cleverest of
      Charcot's followers. He had studied memory extensively, in particular affective
      memory, which caused him to reject Bergson's theories and now makes his work a
      major precursor. Sollier attempted to trigger 'emotional revivals'
      (reviviscences), 'reproducing the entire state of the personality of the subject
      at the time of the initial experience'. This concept was integrated by Proust
      into his novel, with emphasis on 'involuntary memory'. Proust's last neurologist
      was Joseph Babinski, whom he consulted repeatedly because he feared becoming
      aphasic, like his mother. Proust's unusual life journey with the most celebrated
      neurologists of his time highlights aspects of his literary work and also
      provides a unique perspective on the neurological intelligentsia at the turn of
      the 19th century.

PMID- 17213719
TI  - Dementia and art: neuronal intermediate filament inclusion disease and
      dissolution of artistic creativity.
AB  - The paper presents a new case of neuronal intermediate filament inclusion disease
      (NIFID), a recently described new variant of early-onset frontotemporal dementia.
      Documented with repetitive brain images, morphologically proven cases
      additionally endorse evolving the clinical and pathological phenotype of NIFID.
      For the first time the paper describes the probable influence of NIFID on the
      artistic creativity of an accomplished artist showing rapid dissolution of
      artistic talent.

PMID- 17213720
TI  - Development of cerebral infarction shortly after intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Cerebral infarction (CI) occurring soon after
      intracerebral hemorrhage (ICH) has been rarely reported. The purpose of the
      present study was to characterize this condition and discuss the possible
      pathophysiology. METHOD: We retrospectively studied 6 patients who developed CI
      within 10 days after the onset of ICH. RESULTS: The initial ICHs were located in
      the putamen (n=3), thalamus (n=2) and cerebellum (n=1), and were considered to be
      caused by hypertension in all of the patients. They showed sudden worsening (n=4)
      or change in neurologic symptoms (n=2) within 10 days after the initial ICH.
      Follow-up imaging revealed corresponding lacunar (n=2) and territorial (n=4)
      infarcts. Possible factors related to the development of new CIs included
      mechanical compression of cerebral vessels (n=2), dehydration (n=4), hypotension
      (n=2), infection (n=2) and concomitant small-vessel pathology (n=2). CONCLUSIONS:
      ICH may predispose certain patients to the development of infarcts through a
      combination of mechanisms, including mechanical compression of cerebral vessels,
      hemodynamic instability, inflammation and concomitant small-vessel pathology.

PMID- 17213721
TI  - Arterial hypertension in patients with left primary hemifacial spasm is
      associated with neurovascular compression of the left rostral ventrolateral
      medulla.
AB  - The aim of the study was to clarify the relationship between neurovascular
      compression of the rostral ventrolateral medulla and arterial hypertension in
      patients with primary hemifacial spasm. We enrolled 82 patients with primary
      hemifacial spasm and 82 age- and sex-matched magnetic resonance imaging (MRI)
      controls of the posterior cranial fossa. Neurovascular compression of the rostral
      ventrolateral medulla was assessed by MRI, and its association with arterial
      hypertension was investigated. No significant differences were found in
      prevalence of arterial hypertension between patients with primary hemifacial
      spasm and control subjects (39.0 vs. 29.3%, p=0.19). Thirty-two percent of the
      patients with left primary hemifacial spasm (n=44) and 47% of the patients with
      right primary hemifacial spasm (n=38) were hypertensive. Neurovascular
      compression of the left rostral ventrolateral medulla was observed in 86% of
      those with left (ipsilateral) primary hemifacial spasm with arterial hypertension
      (n=14) and 33% of those with left (ipsilateral) primary hemifacial spasm without
      (n=30). The association between neurovascular compression of the left rostral
      ventrolateral medulla and arterial hypertension was significant in patients with
      left (ipsilateral) primary hemifacial spasm (p=0.0012), but not in patients with
      right (contralateral) primary hemifacial spasm (p=0.18). Neurovascular
      compression of the left rostral ventrolateral medulla was more frequently
      observed in hypertensive patients with left primary hemifacial spasm, and
      neurovascular compression of the left rostral ventrolateral medulla correlated
      with arterial hypertension in these patients. These results are of potential
      clinical importance for the treatment of primary hemifacial spasm with arterial
      hypertension.

PMID- 17213722
TI  - Carotid ultrasound criteria for detecting intracranial carotid stenosis.
AB  - BACKGROUND/AIMS: This study attempted to establish carotid ultrasound criteria
      for identifying stenosis of the intracranial internal carotid artery (ICA) and
      middle cerebral artery (MCA). METHODS: Two hundred and fifty-five patients were
      enrolled. Ultrasound measurements for common carotid artery (CCA) and ICA were as
      follows: flow volume (FV), peak systolic velocity (PSV), end-diastolic velocity
      (EDV), pulsatility index (PI) and resistance index (RI). The sensitivity and
      specificity of the ultrasound criteria for determining intracranial ICA or
      MCA>or=50% stenosis were calculated. RESULTS: The criteria identified for
      detecting intracranial ICA>or=50% stenosis were ICA FV<159 ml/min, ICA PSV<33
      cm/s and CCA PSV<42 cm/s. When ICA PSV<33 cm/s was combined with CCA PSV<42 cm/s,
      sensitivity increased to 82%, with 91% specificity. The criteria identified for
      detecting MCA>or=50% stenosis were CCA FV<285 ml/min, ICA FV<179 ml/min, ICA
      PSV<33 cm/s, >35% reduction in FV in the CCA, >40% reduction in FV in ICA, and
      >35% reduction in PSV in ICA. When these criteria were combined, sensitivity
      increased to 69%, with 85% specificity. CONCLUSION: This study demonstrated that
      ultrasound criteria are sensitive and specific for detecting intracranial ICA and
      MCA significant obstruction.

PMID- 17213723
TI  - Influence of motor symptoms upon the quality of life of patients with Parkinson's
      disease.
AB  - We studied the impact of various motor and nonmotor symptoms upon quality of life
      in patients with Parkinson's disease (PD). The study comprised 110 patients with
      PD (age: 68.6 years, course of the disease: 7.6 years). The Unified Parkinson
      Disease Rating Scale (UPDRS; I-IV) and Parkinson's Disease Questionnaire (PDQ-39)
      were recorded. We recorded the correlations between years of disease and UPDRS
      IV, as well as PDQ-39 and UPDRS I, II, III and IV. Introduction of all variables
      into a linear regression model showed that 3 variables accounted for 51% of the
      variance in PDQ-39. Mental condition, gait disorders and complications of
      dopaminergic drugs are the variables that most affect the quality of life of
      patients with PD.

PMID- 17213724
TI  - Cerebrospinal fluid anti-SSA autoantibodies in primary Sjogren's syndrome with
      central nervous system involvement.
AB  - BACKGROUND: Central nervous system involvement in primary Sjogren's syndrome is a
      matter of controversy, and its diagnosis remains difficult. METHODS: We report 3
      patients with primary Sjogren's syndrome and central nervous system involvement
      in whom we assessed intrathecal immunoglobulin G synthesis and the presence of
      cerebrospinal fluid anti-SSA and anti-SSB autoantibodies. RESULTS: We found
      intrathecal immunoglobulin G synthesis and presence of cerebrospinal fluid anti
      SSA autoantibodies in all patients, with demonstration for the first time of
      specific anti-SSA autoantibody intrathecal synthesis in 2 patients. CONCLUSION:
      We suggest that cerebrospinal fluid anti-SSA autoantibodies could serve as a
      biomarker for Sjogren's-syndrome-related central nervous system involvement.

PMID- 17213725
TI  - Efficacy of bioactive polypeptides on bleeding and intra-abdominal adhesions.
AB  - BACKGROUND: Perioperative bleeding and postoperative adhesions are two problems
      encountered in abdominal surgery. Commercial products are available that decrease
      both bleeding and development of abdominal adhesions, but no products are
      effective in both situations. The combination of differently charged bioactive
      polypeptides, administered intraperitoneally, has previously been shown effective
      in decreasing postoperative adhesions. The present study is a pilot examination
      of the effects on perioperative bleeding and postoperative adhesions, applying
      the polypeptide concept. METHODS: Standardized wounds in the liver and spleen
      were induced in 52 NMRI mice. The amounts of bleeding and postoperative adhesions
      were measured after 1 and 7 days, respectively. Separate animals were examined
      after 8 weeks for long-term healing of the parenchymal wounds. RESULTS: Both
      parenchymal bleeding and the extent of adhesions significantly decreased (p =
      0.001 and p = 0.029, respectively) as compared to controls. Histology after 8
      weeks showed no clear signs of impaired or altered healing. CONCLUSION:
      Intraperitoneal administration of differently charged polypeptides significantly
      decreased postoperative bleeding and postoperative adhesions. Bioactive
      polypeptides appear promising in the promotion of peritoneal healing and merits
      further studies.

PMID- 17213726
TI  - A new chemosensitivity assay for ascites tumor cells using a thermoreversible
      gelation polymer as a culture medium and the observed clinical responses.
AB  - BACKGROUND/AIM: Ascites tumor cells from patients with peritonitis carcinomatosa
      were tested for cis-diamminedichloroplatinum (CDDP) sensitivity. The patients
      were divided into CDDP-sensitive and resistant groups. Survival and time to
      progression (TTP) rates were compared. MATERIALS AND METHODS: 18 peritonitis
      carcinomatosa patients with class V ascites based on cytologic diagnosis were
      enrolled in this study. Chemosensitivity testing of the ascites tumor cells was
      done to determine their sensitivity to CDDP using a three-dimensional culture
      matrix of thermoreversible gelation polymer (TGP). CDDP at a dose calculated to
      achieve ascitic fluid drug levels equivalent to the IC(50) was given
      intraperitoneally to 12 CDDP-sensitive patients and 6 CDDP-resistant patients.
      RESULTS: Both the median survival time and the median TTP were significantly
      longer in CDDP-sensitive patients than in CDDP-resistant patients (survival time
      105 vs. 13 days, p = 0.019; TTP 90 vs. 5 days, p = 0.029). CONCLUSION: The
      results indicate the potential feasibility of controlling ascites in cancer
      patients in whom a maximal dose effect can be achieved with a minimal dose of
      chemotherapy.

PMID- 17213727
TI  - Tri-iodothyronine as a stimulator of liver regeneration after partial and
      subtotal hepatectomy.
AB  - BACKGROUND: Tri-iodothyronine (T3) has been shown to be a hepatic mitogen. We
      investigated whether exogenous application of T3 improves liver regeneration
      after 70% partial hepatectomy (PH) and confers a survival advantage after 90%
      subtotal hepatectomy (SH) in rats and whether this is associated with the
      stimulation of angiogenesis. METHODS: Rats were subjected to PH or SH 10 days
      after injection of a single dose of T3. Liver body weight ratio (LBR), hepatic
      proliferation (Ki-67), biochemical markers as well as vascular endothelial growth
      factor (VEGF) expression were assessed by immunohistochemistry. Gene expression
      of pathogenic relevant genes was determined by customized cDNA arrays and
      quantitative RT-PCR. RESULTS: T3-treated rats showed an increased LBR and Ki-67
      index after PH and SH, which reached statistical significance compared to placebo
      treated rats (p < 0.05). On the transcriptional level, T3-treated rats had an
      increased expression of VEGF as demonstrated by immunohistochemistry, which was
      associated with a higher expression of its receptor Flt-1. CONCLUSIONS: Exogenous
      administration of T3 ameliorates liver regeneration after 70% PH and 90% SH,
      possibly due to stimulation of angiogenesis. Therefore, its clinical use might be
      of interest due to its excellent general practicability.

PMID- 17213728
TI  - Normal growth spurt and final height despite low levels of all forms of
      circulating insulin-like growth factor-I in a patient with acid-labile subunit
      deficiency.
AB  - BACKGROUND: In a recently described patient with acid-labile subunit (ALS)
      deficiency, the inability to form ternary complexes resulted in a marked
      reduction in circulating total insulin-like growth factor (IGF)-I, whereas
      skeletal growth was only marginally affected. To further study the role of
      circulating versus locally produced IGF-I in skeletal growth in this patient, we
      now describe in detail growth changes and their relationship with several
      components of the circulating IGF system. DESIGN AND METHODS: We followed growth
      and development up to the final height in a patient with complete ALS deficiency
      and determined both spontaneous and growth hormone (GH)-stimulated changes in the
      IGF system, including measurements of total, free and bioactive IGF-I, total IGF
      II and insulin-like growth factor binding protein (IGFBP)-1, IGFBP-2 and IGFBP-3.
      RESULTS: The patient had a delayed growth and pubertal onset. Six months of GH
      treatment had no effect on growth. At the age of 19.3 years, he spontaneously
      completed puberty and had a normal growth spurt for a late adolescent (peak
      height velocity of 8.4 cm/year). A normal final height was attained at 21.3 years
      (167.5 cm; -0.78 SDS). During as well as after puberty, basal levels of total,
      free and bioactive IGF-I were low, as were total IGF-II, IGFBP-1, IGFBP-2 and
      IGFBP-3. GH treatment for 6 months normalized free IGF-I and increased bioactive
      IGF-I, but had no effect on growth velocity. CONCLUSIONS: This case story shows
      that in the presence of complete ALS deficiency, a height within normal limits
      can be obtained despite low levels of all forms of circulating IGF-I.
      Furthermore, the patient presented a delayed but normal growth spurt without any
      marked increment of circulating IGF-I.

PMID- 17213729
TI  - Body fat estimation using bioelectrical impedance.
AB  - BACKGROUND/AIMS: Although childhood obesity is a major problem, routine
      assessment methods do not reflect fat mass. Body mass index, which is most
      commonly used, gives an indication of weight for height and not a degree of
      adiposity. METHODS: Bioelectrical impedance and dual-energy X-ray absorptiometry
      (DEXA) were used in a group of obese children to assess body fat. RESULTS:
      Comparison between DEXA and commercial bioelectrical impedance scales in 46
      children showed a highly significant correlation (R = 0.944, p < 0.001) in fat
      mass. Fat mass measured using bioelectrical impedance was 2.4 kg lower compared
      to measurement using DEXA. CONCLUSION: These bioelectrical scales may prove
      useful in the management of childhood obesity as they are able to provide
      important clinical information regarding fat mass and adiposity.

PMID- 17213730
TI  - Increased renal expression of aquaporin-3 in rats inhibited type 2 11beta
      hydroxysteroid dehydrogenase.
AB  - AIMS: To investigate whether the regulation of aquaporin (AQP) channels is
      altered by inhibition of type 2 11beta-hydroxysteroid dehydrogenase (11betaHSD2).
      METHODS: Male Sprague-Dawley rats were treated with glycyrrhizic acid (GA, 2 g/l
      drinking water) for 7 days. The expression of AQP2 and AQP3 was determined in the
      kidney by immunoblotting and immunohistochemistry. The expression of Gsalpha and
      type VI adenylyl cyclase, and the activity of adenylyl cyclase were also
      determined. RESULTS: Following the GA treatment, the expression of 11betaHSD2 was
      significantly decreased in the kidney. The expression of AQP3 was increased,
      while that of AQP2 remained unchanged. Plasma renin activity and serum
      aldosterone levels were decreased. Plasma arginine vasopressin (AVP) levels were
      comparable between the groups. Neither the forskolin-stimulated cAMP generation
      nor the expression of Gsalpha and type VI adenylyl cyclase was altered
      significantly. CONCLUSION: A decreased expression of 11betaHSD2 may result in an
      upregulation of AQP3, in which AVP/cAMP-dependent mechanisms are unlikely to be
      involved.

PMID- 17213732
TI  - The unique and independent practice of nursing.

PMID- 17213733
TI  - The movement to secure statutory definition of the unique and independent
      practice of nursing. 1976.

PMID- 17213734
TI  - Aspirin and Plavix: what every clinical nurse specialist should know now.

PMID- 17213735
TI  - Innovation and entrepreneurship: shaping your professional horizon.

PMID- 17213736
TI  - The role of apoptosis in respiratory diseases.
AB  - PURPOSE: The purpose of this article is to define apoptosis and describe how this
      cellular pathway is relevant to the pathogenesis of different respiratory
      diseases. This will assist clinical nurse specialists in understanding how new
      drugs and therapies inhibit and stimulate apoptotic pathways. BACKGROUND:
      Clinical nurse specialists need to expand their knowledge concerning the role of
      apoptosis so that they can better expand their spheres of influence. The 4 stages
      of apoptosis are discussed, as well as the various apoptotic pathways involved
      with asthma, emphysema, and acute respiratory distress syndrome that promote and
      inhibit apoptosis in patients. CONCLUSION: It is crucial for clinical nurse
      specialists to know what apoptosis is and how it relates to different
      pathophysiologic states. The challenge facing clinical nurse specialists is how
      to be kept informed and current concerning molecular and cellular mechanisms that
      are important in the practice setting. Strategies needed to maintain expertise
      include acquiring new knowledge, developing new skills, and changing attitudes
      about molecular biology. Apoptosis must become a significant part of any health
      professionals' continuing educational program because it has been recognized as
      the pathway to most any disease. Clinical nurse specialists who understand
      apoptosis and its pathways can use this knowledge to aid in the prevention and
      treatment of respiratory diseases.

PMID- 17213738
TI  - Perceived readiness for hospital discharge in adult medical-surgical patients.
AB  - PURPOSE: The purpose of the study was to identify predictors and outcomes of
      adult medical-surgical patients' perceptions of their readiness for hospital
      discharge. DESIGN: A correlational, prospective, longitudinal design with path
      analyses was used to explore relationships among transition theory-related
      variables. SETTING: Midwestern tertiary medical center. SAMPLE: 147 adult medical
      surgical patients. METHODS: Predictor variables included patient characteristics,
      hospitalization factors, and nursing practices that were measured prior to
      hospital discharge using a study enrollment form, the Quality of Discharge
      Teaching Scale, and the Care Coordination Scale. Discharge readiness was measured
      using the Readiness for Hospital Discharge Scale administered within 4 hours
      prior to discharge. Outcomes were measured 3 weeks postdischarge with the Post
      Discharge Coping Difficulty Scale and self-reported utilization of health
      services. FINDINGS: Living alone, discharge teaching (amount of content received
      and nurses' skill in teaching delivery), and care coordination explained 51% of
      readiness for discharge score variance. Patient age and discharge readiness
      explained 16% of variance in postdischarge coping difficulty. Greater readiness
      for discharge was predictive of fewer readmissions. CONCLUSIONS: Quality of the
      delivery of discharge teaching was the strongest predictor of discharge
      readiness. Study results provided support for Meleis' transitions theory as a
      useful model for conceptualizing and investigating the discharge transition.
      IMPLICATIONS FOR PRACTICE: The study results have implications for the CNS role
      in patient and staff education, system building for the postdischarge transition,
      and measurement of clinical care outcomes.

PMID- 17213739
TI  - A qualitative evaluation of a family nursing intervention.
AB  - Congestive heart failure is a major source of anxiety for both patients and their
      family. This article presents the results of a qualitative case study aimed at
      evaluating family nursing interventions from the perspective of the family
      members and a clinical nurse specialist (CNS). A CNS applied a family nursing
      intervention program with 4 couples. Data were obtained through semistructured
      interviews preintervention and postintervention for the couples and
      postintervention for the CNS. The transcripts of the interviews were submitted
      for content analysis. For the couples, results show both spouses subject to a
      high level of suffering, which can be alleviated through a family nursing meeting
      that allows them to obtain a better understanding of each other's experience. For
      the CNS, family interventions were considered a privilege since they helped
      relieve suffering and her own feelings of powerlessness. These results have the
      potential to improve family nursing interventions and enhance CNS practice.

PMID- 17213741
TI  - Advanced practice nurses: a new skirmish in the continuing battle over scope of
      practice.

PMID- 17213742
TI  - Clinical nurse specialist profile. Interview by Jo Ellen Rust.

PMID- 17213743
TI  - Gender and strain variations in left ventricular cardiac function and mass
      determined with magnetic resonance imaging at 7 tesla in adult mice.
AB  - OBJECTIVES: We sought to assess with magnetic resonance imaging (MRI) the
      influence of strain type and gender on left ventricular (LV) global function and
      mass in 3 inbred mouse strains with a normal cardiac phenotype. MATERIALS AND
      METHODS: A total of 30 mice from 3 inbred strains (C57BL/6, 29S2/SvPasCrl, and
      C3HFeJ) were studied on a 7.05-T MR scanner using ECG-triggered cine sequences.
      LV mass and volumes were calculated with inclusion and exclusion of papillary
      muscles (PMs) in the LV wall. RESULTS: Significant differences were found with
      strain and gender (P < 0.001), with strain-effect but no gender-effect for
      ejection fraction (EF), end-diastolic volume (EDV), and end-systolic volume
      (ESV). There were no differences in LV mass between strains but lower values in
      female mice except in the C3H strain. The exclusion of PMs led to the relative
      underestimation of EF (-6.1%) and of LV mass (-6.4 mg) and the relative
      overestimation of EDV (6.3 microL) and ESV (5.3 microL). Inter- and intraobserver
      reproducibility was better when PMs were included. CONCLUSION: The use of MRI
      demonstrates cardiac interstrain and gender-related phenotypic diversities that
      are essential factors to consider when building genomic databases and designing
      studies.

PMID- 17213744
TI  - Histogram-based selective deblurring to improve computed tomography imaging of
      calcifications.
AB  - OBJECTIVES: Computed tomography (CT) imaging of small high-density structures,
      eg, calcifications, is hampered by image blur. This study aims to deconvolve
      calcifications in the transverse and longitudinal directions while avoiding noise
      amplification and edge-ringing artifacts in the surrounding low-density
      structures. MATERIALS AND METHODS: A method referred to as histogram-based
      selective deblurring (HiSD) has been developed to generate a restored image by
      combining the low-intensity (ie, Hounsfield Units) information of the original
      image with the high-intensity information of the deconvolved image. HiSD is
      evaluated on phantom and in vitro atherosclerotic plaque CT images by comparing
      the original and restored images with their corresponding reference micro-CT
      images both qualitatively and quantitatively. RESULTS: HiSD reduces calcification
      blur in the transverse and longitudinal directions without introducing noise and
      ringing-artifacts in the surrounding tissues. Calcification area and volume
      measurements are significantly improved in the restored images (reducing on
      average overestimation by 32% and 83%, respectively). CONCLUSIONS: HiSD
      significantly improves CT visualization and quantification of small high-density
      structures imaged in vitro.

PMID- 17213745
TI  - Routine isotropic computed tomography scanning of chest: value of coronal and
      sagittal reformations.
AB  - OBJECTIVE: We sought to evaluate the usefulness of coronal and sagittal
      reformations from isotropic chest computed tomography (CT) examinations. METHODS:
      A total of 30 chest CT examinations were reconstructed into 2 sets of axial
      source images: 0.9-mm slice width with 0.45-mm reconstruction interval
      (isotropic) and 4-mm slices with 3-mm reconstruction interval. The isotropic
      dataset was reformatted into coronal and sagittal stacks with 4-mm slices. Three
      readers reviewed the image sets with 4-mm slice widths. Coronal and sagittal
      reformations were compared at the same sitting to axial images for depiction of
      anatomy and disease in the aorta, pulmonary arteries, hilar regions, mediastinum,
      lung parenchyma, pleura, diaphragm, thoracic spine, ribs, and trachea. A 5-point
      scale was used to determine whether nonaxial reformations showed anatomy and
      disease significantly better, somewhat better, same, somewhat worse or
      significantly worse than equivalent thickness axial source images. A 3-point
      scale was used to score if nonaxial image sets showed no, some, or significant
      additional information compared with the axial plane regarding the main
      diagnosis. RESULTS: There was better visualization of the hilar regions,
      diaphragm, spine, and trachea on the coronal reformations compared with source
      axial images (P < 0.05). Sagittal reformations scored better than axial source
      images for aorta, pleura, diaphragm, spine, and ribs (P < 0.05). The coronal and
      sagittal series showed significant additional information in 11% and 9% of
      patients, respectively. CONCLUSION: Radiologists should consider the use of one
      or both of coronal and sagittal planes in addition to the axial series in routine
      interpretation of chest CT.

PMID- 17213746
TI  - Bipolar radiofrequency ablation using internally cooled electrodes in ex vivo
      bovine liver: prediction of coagulation volume from applied energy.
AB  - OBJECTIVE: We sought to evaluate the relationship between parameters of bipolar
      radiofrequency (RF) ablation using internally cooled electrodes. MATERIALS AND
      METHODS: Bipolar RF ablations (n = 24) were performed in ex vivo bovine liver
      using an internally cooled applicator with 2 electrodes located on the same
      shaft. The power-output was systematically varied (20-75 W). On the basis of our
      experimental data, mathematical functions were fitted and the goodness-of-fit was
      assessed by the parameter R. RESULTS: The duration to induce an increase of
      tissue resistance and the amount of applied energy increased with a decreased
      power-output. The maximum short-axis was 4.5 cm (20 W) and required an
      application of 64 kilojoules (kJ). The volume of coagulation can be determined as
      a function of the duration of energy application (R = 0.954) and the amount of
      applied energy (R = 0.945). CONCLUSION: The amount of applied energy and the
      duration of energy application can predict the volume of induced coagulation and
      may be useful to control internally cooled bipolar RF ablation.

PMID- 17213747
TI  - Rapid lung volumetry using ultrafast dynamic magnetic resonance imaging during
      forced vital capacity maneuver: correlation with spirometry.
AB  - INTRODUCTION: Dynamic magnetic resonance imaging (MRI) has the potential for
      rapid noninvasive evaluation of changes in lung volume. The aim of this study was
      to perform rapid lung volumetry using ultrafast dynamic MRI to capture a forced
      vital capacity (FVC) maneuver. MATERIALS AND METHODS: Nine healthy volunteers
      underwent 2-dimensional spoiled gradient echo imaging in coronal and sagittal
      planes during FVC maneuvers. An elliptical model of the axial cross section of
      the lungs was used to generate rapid volume-time curves. Spirometric indices were
      correlated with MR volumetry findings. RESULTS: Total lung volume calculated from
      static MRI correlated well with the dynamic MR scans (r = 0.83; P < 0.01).
      Spirometric indices (first second of forced expiration and FVC) calculated from
      our MR volumetry technique correlated well with conventional spirometry (P <
      0.01). CONCLUSION: The technique provides a means of sampling lung volume change
      during the rapid subsecond movements that take place during a FVC maneuver.

PMID- 17213748
TI  - Validation of semiautomatic measurement of the extent of breast tumors using
      contrast-enhanced magnetic resonance imaging.
AB  - OBJECTIVES: The aim of this study was to assess whether the semiautomatic
      measurement of breast-tumor extent using contrast-enhanced magnetic resonance
      imaging (CE-MRI) decreases measurement variation compared with manual evaluation
      and increases precision with respect to tumor extent measured at histopathology.
      MATERIALS AND METHODS: Forty-three patients who underwent breast-conserving
      therapy for 46 tumors were consecutively included. Extended histopathology
      analysis was performed on the excision specimens. Two experienced breast-MR
      radiologists independently manually assessed the largest diameter of the tumors
      at preoperative CE-MRI. Two observers used a semiautomatic segmentation technique
      to independently obtain the largest diameter and the volume of the tumors.
      RESULTS: Semiautomatic volumetric measurement of tumor volume was more accurately
      correlated with histopathology (adjusted R-square 0.84 and 0.81) compared with
      conventional measurement (adjusted R-square 0.56 and 0.70) and semiautomatic
      measurement (adjusted R-square 0.63 and 0.60) of the largest diameter of the
      tumor. The interobserver variability between the volumetric measurements was
      significantly smaller than the interobserver variability between the largest
      diameter measurements of tumor extent obtained by the radiologists (P < 0.001).
      CONCLUSIONS: Semiautomatic volumetric measurement of breast-tumor extent at CE
      MRI provides a more accurate assessment of tumor extent with respect to
      histopathology and reduces measurement variation compared with manual assessment
      of the largest diameter. Automated volumetric measurement thus provides potential
      for increased precision in establishing response to treatment.

PMID- 17213749
TI  - High-resolution three-dimensional magnetic resonance imaging of mouse lung in
      situ.
AB  - OBJECTIVES: This study establishes a method for high-resolution isotropic
      magnetic resonance (MR) imaging of mouse lungs using tracheal liquid-instillation
      to remove MR susceptibility artifacts. METHODS: C57BL/6J mice were instilled
      sequentially with perfluorocarbon and phosphate-buffered saline to an airway
      pressure of 10, 20, or 30 cm H2O. Imaging was performed in a 7T MR scanner using
      a 2.5-cm Quadrature volume coil and a 3-dimensional (3D) FLASH imaging sequence.
      RESULTS: Liquid-instillation removed magnetic susceptibility artifacts and
      allowed lung structure to be viewed at an isotropic resolution of 78-90 microm.
      Instilled liquid and modeled lung volumes were well correlated (R = 0.92; P <
      0.05) and differed by a constant tissue volume (220 +/- 92 microL). 3D image
      renderings allowed differences in structural dimensions (volumes and areas) to be
      accurately measured at each inflation pressure. CONCLUSION: These data
      demonstrate the efficacy of pulmonary liquid instillation for in situ high
      resolution MR imaging of mouse lungs for accurate measurement of pulmonary
      airway, parenchymal, and vascular structures.

PMID- 17213750
TI  - Clinical safety and diagnostic value of the gadolinium chelate gadoterate
      meglumine (Gd-DOTA).
AB  - OBJECTIVE: The purpose of this study was to assess the diagnostic value and
      safety of the contrast agent gadoterate meglumine (Gd-DOTA, DOTAREM, Guerbet,
      Roissy CdG Cedex, France) in the setting of a postmarketing surveillance study.
      MATERIALS AND METHODS: Between January 2004 and October 2005, radiologists in 61
      radiologic institutions were asked to document the routine use of Gd-DOTA in a
      questionnaire. In addition to assessing the image quality and diagnostic value of
      the contrast-enhanced magnetic resonance imaging scans, we statistically
      evaluated and analyzed demographic and safety data. RESULTS: A total of 24,308
      patients were intravenously injected with Gd-DOTA for various diagnostic
      examinations. The examination allowed for establishing a diagnosis in >99% of
      cases and image quality was rated as "excellent" or "good" in 97.5% of all cases.
      Adverse events were noted in only 0.4% of the examinations and were mostly rated
      as minor, such as feeling of warmth or taste alteration. There was one serious
      adverse event, albeit with complete recovery. CONCLUSION: This postmarketing
      surveillance study suggests diagnostic efficacy and a favorable clinical safety
      profile of Gd-DOTA in clinical practice.

PMID- 17213751
TI  - Menopause, but not age, is an independent risk factor for fasting plasma glucose
      levels in nondiabetic women.
AB  - OBJECTIVE: Glucose metabolism is influenced by various genetic and environmental
      factors. In women the prevalence of abnormal glucose metabolism is known to
      increase around and after age 50. The aim of this study was to determine whether
      menopause augments fasting plasma glucose (FPG) levels in women. DESIGN: Of 672
      Japanese women who underwent health examinations, we studied 505 nondiabetic
      participants who had no history of hysterectomy and had never used estrogens or
      progestins. All participants were administered an oral glucose tolerance test,
      and their blood measurements and information about their menopause status were
      obtained. RESULTS: Of these 505 women, 208 were premenopausal and 297 were
      postmenopausal. Age, body mass index, triglycerides level, total cholesterol
      level, low-density lipoprotein cholesterol level, blood pressure, and homeostasis
      model assessment insulin sensitivity index rose across quintiles of FPG levels,
      whereas high-density lipoprotein cholesterol level and homeostasis model
      assessment pancreatic beta-cell function index did not. The number of
      premenopausal women declined and the number of postmenopausal women increased
      across quintiles of FPG levels. Univariate regression analysis demonstrated that
      age, body mass index, triglycerides level, low-density lipoprotein cholesterol
      level, and menopause status were associated with FPG level, whereas high-density
      lipoprotein cholesterol level was not. Stepwise multivariate regression analysis
      showed that the independent risk factors for elevated FPG levels were body mass
      index, menopause, and triglycerides level, whereas age and low-density
      lipoprotein cholesterol level did not contribute to FPG levels. CONCLUSIONS:
      Menopause, but not age, is directly involved in augmented FPG levels in
      nondiabetic women.

PMID- 17213752
TI  - Effects of soy protein isolate and moderate exercise on bone turnover and bone
      mineral density in postmenopausal women.
AB  - OBJECTIVE: The aim of this study was to assess the independent and additive
      effects of soy protein isolate (SPI) and moderate-intensity exercise (EX) on bone
      turnover and bone mineral density (BMD). DESIGN: This study used a placebo
      controlled, double-blind (soy), randomized 2 (SPI vs milk protein isolate [MPI])
      x 2 (EX vs no EX) design. Sixty-one postmenopausal women were randomized, and 43
      (62 +/- 5 y) completed the 9-month intervention (SPI, n = 10; MPI, n = 12; SPI +
      EX, n = 11; MPI + EX, n = 10). Serum C-terminal cross-linked telopeptides of type
      I collagen and serum bone-specific alkaline phosphatase were measured as markers
      of bone resorption and formation, respectively. BMD was measured by dual-energy x
      ray absorptiometry. RESULTS: At 9 months, SPI reduced serum C-terminal cross
      linked telopeptides (-13.3% +/- 15.3% vs -1.5% +/- 21.0%; P = 0.02) and serum
      bone-specific alkaline phosphatase (-4.7% +/- 14.7% vs 6.5% +/- 17.7%; P = 0.02)
      compared to milk protein isolate. EX attenuated the reduction in serum C-terminal
      cross-linked telopeptides (-1.9% +/- 21.6% vs -12.4% +/- 15.3%; P = 0.04);
      however, no EX effects were apparent in serum bone-specific alkaline phosphatase
      at 9 months (2.8% +/- 16.1% vs -1.0% +/- 18.3%; P = 0.28). Neither SPI nor EX
      affected BMD at any site; however, change in BMD was related to change in fat
      mass (r = 0.40, P < 0.05). CONCLUSIONS: In postmenopausal women (1) SPI reduces
      bone turnover with no impact on BMD over 9 months; (2) moderate-intensity
      endurance exercise training did not favorably alter bone turnover and had no
      impact on BMD; and (3) there were no additive effects of soy and exercise on bone
      turnover or BMD.

PMID- 17213753
TI  - Hot flashes are associated with increased ambulatory systolic blood pressure.
AB  - OBJECTIVE: To determine the association between ambulatory blood pressure (BP)
      and hot flash experience. DESIGN: The participants in the study were 154 women
      (mean age=46 years, range=18-65 years), who were evaluated as part of a cross
      sectional study on ethnicity, socioeconomic status, and diurnal BP patterns.
      Participants could be either normotensive or mildly hypertensive. Participants
      wore an ambulatory BP monitor for 24 hours and recorded their awake and sleep
      times. Hot flashes were assessed using an everyday complaint questionnaire that
      embeds symptoms associated with menopause into a list of everyday complaints.
      RESULTS: Thirty-three percent of participants reported having had hot flashes
      during the 2 weeks before they completed the questionnaire. Compared with women
      who did not report hot flashes, mean awake and sleep systolic BP values were
      significantly higher (P<0.004 and P=0.007, respectively) in women who reported
      having had hot flashes. Hot flashes continued to independently predict average
      awake and sleep systolic BP (both P=0.03) after controlling for age,
      race/ethnicity, body mass index, and menopausal status. Hot flashes were not
      associated with diastolic BP or nocturnal dipping of BP. CONCLUSIONS: Hot flashes
      are associated with increased awake and sleep systolic BP independent of
      menopausal status. Further investigation is warranted to elucidate the mechanisms
      by which hot flashes are associated with BP.

PMID- 17213754
TI  - The special extract ERr 731 of the roots of Rheum rhaponticum decreases anxiety
      and improves health state and general well-being in perimenopausal women.
AB  - OBJECTIVE: To investigate the efficacy of the special extract ERr 731 from the
      roots of Rheum rhaponticum compared with placebo on anxiety, health state, and
      general well-being in perimenopausal women. DESIGN: This study is a multicenter,
      prospective, randomized, double-blind, placebo-controlled clinical trial, in
      which 109 perimenopausal women with climacteric complaints and anxiety received
      either 1 enteric coated tablet of ERr 731 (n=54) or placebo (n=55) daily for 12
      weeks. The Hamilton Anxiety Scale, the Menopause Rating Scale II, the Women's
      Health Questionnaire, and the Psychological General Well-Being Index were used to
      measure anxiety, health state, and subjective psychological well-being. RESULTS:
      The results demonstrate that ERr 731 is highly effective in reducing anxiety in
      perimenopausal women compared with placebo. After 12 weeks, the Hamilton Anxiety
      Scale total score decreased significantly with ERr 731 (from 27.5+/-6.8 to 9.4+/
      4.2 points) compared with placebo (from 25.1+/-6.0 to 21.6+/-8.6 points). ERr 731
      also reduced the Hamilton Anxiety Scale factor scores for somatic and psychic
      anxiety. After 12 weeks, a reduction in the severity of anxiety from "moderate"
      or "severe" to "slight" was observed in 33 of 39 ERr 731 women completing the
      double-blind phase, which correlated well with the reduction in number and
      severity of hot flushes. This was reflected by a high rate of ERr 731 women
      reporting a marked improvement in health state and general well-being.
      CONCLUSIONS: ERr 731 is an effective medication for women with menopause-related
      anxiety and improves their health state and general well-being.

PMID- 17213755
TI  - [And if tomorrow was dynamic].

PMID- 17213756
TI  - Accuracy of delayed post-contrast FLAIR MR imaging for the diagnosis of
      leptomeningeal infectious or tumoral diseases.
AB  - AIMS: To compare unenhanced, gadolinium enhanced, delayed gadolinium enhanced
      FLAIR images, gadolinium enhanced and delayed gadolinium enhanced T1 images in
      different types of leptomeningeal diseases, and to determine the most accurate
      MRI sequence for the diagnosis of leptomeningeal disease. MATERIAL: and methods:
      Ten patients (6 men, 4 women, age: 52,7+/-16,4) clinically suspected of cerebral
      leptomeningeal infectious or tumoral disease underwent brain MR examination:
      Axial FLAIR and T1 SE images were acquired before, immediately after
      administration of gadobenate dimeglumine (0.1 mmol per kilogram of body weight)
      (early enhancement), and 20 minutes after injection of contrast media (delayed
      enhancement). Images were analysed to determine the more appropriate technique
      for the diagnosis of leptomeningeal disease. RESULTS: Early enhanced FLAIR and
      delayed enhanced T1 were always more or equally accurate for the diagnosis of
      leptomeningeal diasease, as compared to, respectively, unenhanced FLAIR and early
      enhanced T1 images Delayed enhanced FLAIR was always more accurate for the
      diagnosis of leptomeningeal disease as compared to early enhanced FLAIR images.
      Delayed enhanced FLAIR was in most of the cases more accurate for the diagnosis
      of leptomeningeal disease as compared to delayed enhanced T1 images. CONCLUSION:
      Delayed enhanced FLAIR MR sequence seems to improve the diagnosis of
      leptomeningeal infectious or tumoral diseases as compared to other MR sequences.

PMID- 17213757
TI  - Value of phase contrast magnetic resonance imaging for investigation of cerebral
      hydrodynamics.
AB  - OBJECTIVE: Phase Contrast Magnetic Resonance Imaging (PCMRI) is a noninvasive
      technique that can be used to quantify variations of flow during the cardiac
      cycle. PCMRI allows investigations of blood flow dynamics in the main arteries
      and veins of the brain but also the dynamics of cerebrospinal fluid. These
      cerebral flow investigations provide a description of the regulation mechanisms
      of intracranial pressure during the cardiac cycle. The objective of this paper is
      to describe the contribution of this technique in diseases related to disorders
      of cerebral hydrodynamics in the light of 5 clinical cases. METHOD: Flow
      measurements were performed using PCMRI sequences on a 1.5 Tesla MR imager in 4
      patients with symptomatic ventricular dilation and 1 patient with a syringomyelic
      cavity. RESULTS: Flow quantification in these 5 patients, representative of the
      diseases mainly concerned by cerebral hydrodynamics, is useful to guide the
      indication for ventricular shunting in patients with hydrocephalus, to
      demonstrate obstruction of the cerebral aqueduct, to demonstrate recirculation of
      ventricular CSF after ventriculostomy and to characterize the dynamic features of
      CSF inside a spinal cavity. CONCLUSION: PCMRI, now available to neurosurgeons, is
      complementary to morphological MR and provides quantitative information on
      cerebral hydrodynamics. This information is mainly used to confirm alteration of
      CSF flow in the cerebral and spinal compartments. PCMRI is also a functional tool
      to better understand the pathophysiology of hydrocephalus and syringomyelia.

PMID- 17213758
TI  - [Cerebral hydatid disease: imaging features].
AB  - Cerebral hytatid cysts (HC) are extremely rare, forming 2% of all intra cranial
      space occupying lesions even in counties where the disease is endemic. HC
      diagnosis is usually based on a pathognomonic computed tomography (CT) pattern.
      In order to assess the value of MR we reviewed the CT (n=25) and magnetic
      resonance (MR, n=4 including diffusion and proton magnetic resonance spectroscopy
      in 1) imaging of 25 patients with pathologically confirmed cerebral hydatid
      disease. 19 HC were seen in children under 16 years. All were supra tentorial
      with 22 in the middle cerebral artery territory. HC was solitary in 18 cases,
      unilocular in 23 and multi-vesicular in 2 with heavily calcified pericyst in 1. 2
      cysts were intra ventricular and 1 intra aqueducal. The most typical features
      were well defined, smooth thin walled spherical or oval cystic lesions of CSF
      density and/or signal with considerable mass effect (20/25). Surrounding oedema
      with complete or incomplete rim enhancement was seen in 3 cases which were
      labelled as complicated and/or infected cysts. Although CT is diagnostic of
      hydatid disease in almost all cases (22/25), MRI including diffusion and
      spectroscopy precisely demonstrate location, number, cyst capsule, type of signal
      and enhancement and allows diagnosis of atypical or complicated HC and appears
      more helpful in surgical planning.

PMID- 17213759
TI  - [Vertebrovertebral arteriovenous fistula diagnosis and treatment: report of 8
      cases and review of the literature].
AB  - Vertebrovertebral Arteriovenous Fistula (V.V.A.V.F.) is a relatively rare entity.
      It may be an incidental finding or be detected in patients presenting with
      pulsatile tinnitus, cervical bruit, or vertebro-basilar insufficiency. It can be
      spontaneous but it most frequently is post-traumatic in etiology. The authors
      report 8 patients, 4 women and 4 men aged between 20 to 77 years, with 4 post
      traumatic V.V.A.V.F. and 4 spontaneous V.V.A.V.F. that were seen over a 15 year
      period. Imaging work-up included Doppler US (n=4), MRI 9n=3) and angiography
      (n=8). Seven of 8 patients were treated successfully using an endovascular
      technique (5 with balloon occlusion, 1 with coil embolization and 1 using a
      mechanical maneuver), without complication or recurrence, except in one case. We
      compare our results with published reports from the literature and review the
      underlying pathology and management strategies of V.V.A.V.F.

PMID- 17213760
TI  - Endovascular treatment of ruptured posterior circulation dissecting aneurysms.
AB  - BACKGROUND: and aim: Dissecting aneurysms of the posterior circulation constitute
      a relatively uncommon subgroup of aneurysms. They account for 3-7% of cases of
      nontraumatic subarachnoid hemorrhage. Because of high risk, in most cases the
      patients require surgical or endovascular therapy. In this study we discuss the
      clinical efficacy of endovascular treatment with long-term follow-up in ruptured
      dissecting aneurysms of the posterior circulation. MATERIALS AND METHODS: This
      retrospective study was conducted at our institution between January 1995 and
      June 2005. Eight patients (4 male; 4 females) ranging in age from 24 to 65 years
      (mean, 46.75 years), were included. All presented with SAH. Endovascular
      treatment was based on the configuration of the dissecting aneurysm. Attempt was
      made to occlude the dissecting aneurysm. RESULT: A total of 8 ruptured dissecting
      aneurysms in the posterior circulation were treated. Out of them 5 were in the
      intradural vertebral artery, 2 in the basilar trunk and one in the proximal PCA.
      All the cases were technically successful. We have seen only two complications.
      The pre and post procedure (at the time of discharge) mean modified Rankin scores
      in the patients were 4.6 (SD 0.51) and 1.7 (SD 1.98). This improvement in Rankin
      score after endovascular treatment was statistically significant (Wilcoxon signed
      rank test, P=.017). CONCLUSION: Endovascular management of these lesions is safe
      and effective mode of treatment and gives adequate protection from rebleed.

PMID- 17213761
TI  - [Payment by activity and financing of innovative hospital procedures: does the
      new payment system cover endovascular treatment for cerebral aneurysms?].
AB  - METHOD: We have calculated all hospital expenses related to treated intracerebral
      aneurysms for 2005. Catheters, microcatheters, and guidewires as well as coils
      were included. We have compared these expenses to the payment by activity and fee
      per service collected for providing these services. RESULTS: Payments received
      covered only a third of the expenses for the supplies used. Three types of
      expenses are not reimbursed: the guiding material, the coils used but not
      released, and the latest generation of coils not yet added to the national list
      of covered devices. These expenses are also not covered by the payment received
      for the hospital admission. DISCUSSION: Endovascular management of intracranial
      aneurysms has become the treatment of choice over the recent years. This
      treatment is virtually only available in university hospitals. With the current
      mode of reimbursement, such treatment generates losses to the hospital.
      CONCLUSION: This example raises the question of financial support for innovative
      treatments and procedures.

PMID- 17213762
TI  - Giant solitary fibrous tumour of the meninges: MR-pathological correlation.
AB  - The authors present the clinical, MR imaging and pathological features of the
      largest intracranial solitary fibrous tumour of the meninges ever reported in the
      literature. This well-circumscribed dural-based tumour strikingly demonstrated
      two different solid components. The first one demonstrated a suggestive T2
      hypointensity that strongly enhanced after gadolinium administration while the
      other showed more classic homogeneous T2 hyperintensity and mild enhancement.
      These two components were also identifiable on the pathological examination,
      allowing an interesting imaging-histological correlation. Differential diagnoses
      of this rare extra-axial lesion are discussed.

PMID- 17213763
TI  - [Congenital absence of a cervical pedicle].

PMID- 17213765
TI  - [The french model for organized screening for breast cancer: the specifications
      have been published].

PMID- 17213766
TI  - [External phased-array MR imaging preoperative assessment of rectal cancer].
AB  - The main problem associated with rectal cancer treatment is tumor recurrence.
      Randomized controlled studies have shown that adjuvant preoperative radiation
      therapy is effective for reducing local recurrence. These studies have also
      demonstrated that there are groups of rectal cancer patients with differing
      degrees of risk for local recurrence. At one end of the spectrum is the low-risk
      group: patients with superficial rectal cancer, who can be treated with surgery
      alone. At the other end is the high-risk group: patients with a close or involved
      resection margin at total mesorectal excision, the very advanced tumors that
      require a longer course of chemotherapy and radiation therapy, and extensive
      surgery. Paramount for this selection and differentiated treatment is a reliable
      preoperative test that can be used to distinguish these groups of patients. In
      this review article, we will discuss the role of high-resolution phased array MRI
      among the other imaging modalities such as endorectal MRI, endorectal US, and CT.
      We will also discuss and illustrate MR imaging results in terms of T stage,
      circumferential resection margin, locally advanced rectal cancer, and N stage.

PMID- 17213767
TI  - [Improving overall patient care during imaging studies: the radiologist's CREDO
      and PERLES].
AB  - The protocols specifying the basic rules of the doctor-patient relationship that
      have been proposed in the literature are primarily intended for referring
      physicians, in particular oncologists. With regard to the improving radiologists'
      communication skills, a simple tool, RADPED, was developed to help residents in
      pediatric radiology to memorize the main points of the patient-radiologist
      interaction. We suggest a protocol, CREDO, more precisely appropriated to the
      everyday practice of medical imaging, in particular in oncology. This protocol
      relates not only to the radiologist-patient relationship, but also to the rules
      common to the department's entire team. The aims are to establish a partnership
      with the patient (for this purpose, we suggest using the PERLES model:
      partnership, excuses (apology), respect, legitimization, empathy, support),
      carrying out the examination under optimal conditions, listening to what the
      patient has to say, giving information and, above all, organizing the imaging
      department around the patient.

PMID- 17213768
TI  - [Diffusion-weighted imaging of the brain: normal patterns, traps and artifacts].
AB  - Owing to its rapid acquisition time and high sensitivity, diffusion-weighted
      imaging has turned into a routine sequence for brain imaging. This is the case
      not only for stroke, but also for various diseases such as abscesses or tumors.
      Being aware of the artifacts is important for optimal interpretation. After a
      brief review of the normal patterns, the most frequent artifacts, inherent to the
      echoplanar imaging technique, are described and we provide suggestions to avoid
      them. Most current traps are caused by T2-weighting of the diffusion images; the
      key for avoiding erroneous interpretation relies on the ADC map.

PMID- 17213769
TI  - [Ultrasound examination of breast microcalcifications: luxury or necessity?].
AB  - PURPOSE: Determine the value of ultrasound for the diagnosis of isolated breast
      microcalcifications. MATERIAL AND METHODS: Fifty clusters of microcalcifications,
      including 25 smaller than 10 mm, were examined by ultrasound (5-13 MHz) prior to
      stereotactic aspiration macrobiopsy (30 benign lesions, three borderline lesions,
      and 17 malignant lesions, including ten in situ lesions and seven invasive
      lesions). Mammography had placed 13 of these cases in BI-RADS 3, 24 in BI-RADS 4,
      and 13 in BI-RADS 5. The BI-RADS classification was also used for ultrasound
      assessment. RESULTS: Six of the 18 microcalcifications that were not seen by
      ultrasound were malignant (two invasive ductal cancers [IDC] and four ductal
      carcinomas in situ [DCIS]). Two of the four cases with no sonographically visible
      tissue mass proved to be malignant (one IDC, one DCIS); these two lesions had
      been classified BI-RADS 4 and 5 by mammography and were larger than 10 mm.
      Ultrasound visualized 16 masses classed BI-RADS 3, ten masses classed BI-RADS 4,
      and two masses classed BI-RADS 5. One of the lesions classified as BI-RADS 3 by
      mammography was an IDC that was classed BI-RADS3 by ultrasound. Four of the
      lesions classed BI-RADS 4 by mammography were malignant (three were classified BI
      RADS3 by ultrasound while one was classed BI-RADS4). One benign lesion was
      classified BI-RADS 5 by ultrasound. Four cancers were mammographically classed BI
      RADS 5; ultrasound was in agreement in one case but classed three of the cases as
      BI-RADS 4. In one case, ultrasound gave a diagnosis of benignity (BI-RADS 3
      classification). CONCLUSION: Ultrasound is unsuited for the diagnosis of
      microcalcifications because it fails to visualize a mass in one-third of cancers
      and the existence of a mass is correlated with malignancy in one-third of cases.
      Furthermore, US does not correct the false-negative errors of mammography, and it
      underestimates the rate of malignancy by ascribing a benign appearance to 50% of
      cancers, which mammography correctly classifies BI-RADS 4 or 5.

PMID- 17213770
TI  - [Role of embolization in renal angiomyolipomas].
AB  - OBJECTIVE: The purpose of this study is to present the role of embolization in
      the treatment of renal angiomyolipoma (AML) in cases of hemorrhage and to prevent
      bleeding. METHODS: Over a period of 10 years, 35 AMLs in 34 patients, recruited
      in two medical centers, were treated with embolization: 16/35 AML were treated
      urgently to stop bleeding, and 19/35 AML had preventive embolization. Six
      patients were completely asymptomatic and 13 had a history of previous hematoma
      or flank pain. Catheterization was highly selective in all cases (coaxial
      microcatheter in 19 cases), and for embolization we used nonresorbable
      microparticles, coils, and alcohol. RESULTS: When patients presented with acute
      bleeding, embolization was efficient in 80% of cases; another embolization was
      necessary in two cases, and surgery in two others. In six of these cases, surgery
      was planned and done at a later date. When treatment was preventive, one
      embolization was necessary in 17 cases, and two embolizations per case were
      necessary in the other two. Over a period of 18 months of follow-up, we observed
      a 28% decrease in tumor volume; four patients were treated by surgery at a later
      date. CONCLUSION: Embolization is the technique of choice to treat a bleeding AML
      urgently. When preventive treatment is considered, in symptomatic or asymptomatic
      AML, embolization can be an alternative for surgery, but more data is needed to
      specify its proper place in the management of these tumors.

PMID- 17213771
TI  - [Hydatid cyst of the mediastinum: 14 case reports].
AB  - PURPOSE: The objective of this study was to describe the different radiological
      features of the hydatid cyst of the mediastinum. MATERIALS AND METHODS: We
      conducted a retrospective study on 14 patients (seven women, seven men),
      diagnosed with mediastinal hydatid cyst, aged 13-67 years (mean, 48 years) over a
      period of 16 years in our hospital where 71 cases of hydatid disease are annually
      diagnosed. The patients were explored by chest radiography (n=14), chest
      ultrasonography (n=10), abdomen ultrasonography (n=14), computed tomography (CT
      scan) (n=13), and magnetic resonance imaging (MRI) (n=8). RESULTS: The chest x
      ray showed an opacity of the anterior (n=11), middle (n=1), and posterior (n=1)
      mediastinum. The thoracic ultrasound confirmed the liquid nature of the mass with
      a multivesicular aspect (n=9). CT and thoracic MRI made it possible to precisely
      locate the mediastinal compartment involved and study the relationship to
      adjacent structures. A purely mediastinal location was found in only six cases.
      In the remaining cases, it was associated with hepatic (n=7) and pleural (n=1)
      locations. CONCLUSION: Hydatid cysts of the mediastinum are very uncommon.
      Diagnosis can be made by chest sonography. CT scan is the main tool for diagnosis
      and the study of possible extension. Our study showed a more frequent location to
      the anterior mediastinum.

PMID- 17213772
TI  - [Isolated lesion of the infraspinatus at the myotendinous junction: a new
      lesion].
AB  - PURPOSE: We have identified a previously unpublished lesion of the infraspinatus
      muscle at the myotendinous junction. We describe its presentation and MRI
      appearance, notably the absence of other tendinous pathology in the rotator cuff.
      MATERIALS AND METHODS: We retrospectively reviewed 25 patients with isolated
      infraspinatus lesions and associated edema identified on the fat-suppressed T2
      weighted images of MRI. Imaging exams and medical records collected over a 7-year
      period were reviewed by a team of radiologists and surgeons specializing in the
      shoulder. A presentation of the mechanism of injury, radiological analysis of MRI
      scans and other investigations (arthro-CT and EMG studies) were carried out; all
      MRI included at least two fat-suppressed T2-weighted (transverse and coronal)
      sequences and one T1-weighted (transverse) sequence. RESULTS: The lesion was
      characterized by tearing or delamination at the myotendinous junction, which was
      accompanied by edema of the infraspinatus muscle in the initial phase. Over time
      the edema was seen to resolve and muscle atrophy and fatty degeneration became
      predominant. We identified two groups by the onset of their symptoms. In the
      "chronic" group (44%), onset was gradual, with these patients frequently having
      had one or more infiltrations at presentation to us. In the "acute" group (56%),
      there was an initial traumatic event that was variable in intensity and
      mechanism. CONCLUSION: This isolated lesion of the infraspinatus at the
      myotendinous junction has not been previously described. It is recognized by its
      characteristic MRI appearance and is not generally seen on CT arthrograms as
      there is no communication with the joint. Its natural history appears to be of a
      progression from edema to fatty degeneration with or without myotendinous
      retraction and scarring. Its etiology has not yet been clearly established.

PMID- 17213773
TI  - [Imaging of cerebrotendinous xanthomatosis].
AB  - Cerebrotendinous xanthomatosis is a rare lipid storage disorder due tocaused by
      an autosomal recessive inherited defect of the hepatic mitochondrial sterol 27
      hydroxylase. It's characterized by accumulation of cholestanol and cholesterol in
      many tissues, in particular tendons and brain, with tendon xanthomas, juvenile
      cataracts, and neurological abnormalities. MR imaging showed typical bilateral
      and symmetrical involvement of the dentate nuclei. Early and long- term treatment
      may improve neurologic function. The authors present a case of cerebrotendinous
      xanthomatosis and describe ultrasound, computed tomography, and magnetic
      resonance findings.

PMID- 17213774
TI  - [Malignant paraganglioma with vertebral and skull metastasis].
AB  - A paraganglioma is a rare tumor composed of chromaffin cells. Malignant
      paraganglioma is a very rare presentation diagnosed by local recurrence after
      total resection of the primary mass or findings of distant metastasis. We report
      a case of a 30-year-old man who had undergone a carotid body tumor resection 10
      years before and who presented to us with recurrence of the tumor associated with
      lymph node, vertebra and skull metastasis. The diagnosis of malignant
      paraganglioma was based on loco-regional and distant metastasis.

PMID- 17213775
TI  - [Torsion of an epiploic appendage inside a Spigelian hernia: a first imaging case
      report].
AB  - We present the first case illustred in imaging of an epiploic appendage torsion
      inside a Spigelian hernia.

PMID- 17213776
TI  - [Inflammatory pseudotumor of the spleen and radiopathologic correlation].
AB  - Inflammatory pseudotumors of the spleen (IPTS) are rare. We report a case of an
      IPTS in a 48-year-old woman who was admitted for drug eruption. During her
      hospitalization, she complained of abdominal pain. Physical examination and
      laboratory investigations were unremarkable. The abdominal ultrasonography and
      hepatic MRI detected a heterogeneous mass in the spleen measuring approximately 5
      cm in diameter. Partial splenectomy was performed. Histologically, the splenic
      mass was composed of an admixture of inflammatory cellular elements with
      hemorrhage and sclerosis, suggestive of an IPTS. The postoperative course was
      uneventful. The authors attempt to make a radiopathologic correlation of this
      rare tumor.

PMID- 17213777
TI  - [What is your diagnosis? Small intestinal occlusion caused by Ascaris].

PMID- 17213778
TI  - [Breast cancer screening: what can we say today about expected benefits?].

PMID- 17213779
TI  - [Breast cancer screening: when the rear-guard places itself in the vanguard...].

PMID- 17213781
TI  - [Impact of metabolic syndrome on chronic kidney disease].
AB  - Metabolic syndrome has been recognized as possible risk factor for renal damage
      and the increased prevalence of both metabolic syndrome and renal disease
      justifies the increasing interest of the nephrology community toward the
      metabolic syndrome as another possible inducing cause of chronic renal disease,
      although the available evidence about a direct causal relationship between
      metabolic syndrome and development of renal disease so far is scanty. The not
      easy separation of the negative effects on renal function of metabolic syndrome
      from those derived from hypertension and diabetes per se, however, does not
      reduce the interest toward a possible direct impact of metabolic syndrome on
      renal disease. This also in consideration that other important factors linked
      with metabolic syndrome, such as for example obesity, have direct independent
      impact on the development of abnormalities such as microalbuminuria and or overt
      renal disease. Planning of clinical trials specifically for patients with
      metabolic syndrome could be helpful to give definitive answers on a possible
      direct impact of metabolic syndrome on chronic renal disease.

PMID- 17213782
TI  - Anxiety, musculoskeletal and visual disorders in video display terminal workers.
AB  - AIM: The increase in the working population assigned to video display terminals
      (VDT) has led to ever growing attention to reports on health effects. We studied
      musculoskeletal and visual disorders and levels of anxiety in 2 groups of VDT
      operators with different tasks, in order to evaluate if they could be influenced
      by organizational and intrinsically working factors. METHODS: The study included
      190 VDT operators, subdivided into 2 groups (A and B) on the basis of tasks
      performed and average hours/ week spent at VDT (25 vs 36), and 190 controls not
      assigned to VDT. Ocular and musculoskeletal subjective symptoms and objective
      findings were assessed for all subjects, and the State-Trait Anxiety Inventory
      (STAI) test was administered. RESULTS: For VDT operators of the 2 groups, the
      relationship between ocular and musculoskeletal symptoms and findings, working
      life (P=0.0001) and number of hours spent at the VDT (symptoms P=0.001 and
      P=0.0001; findings P=0.002 and P=0.007), was significant. Group B VDT operators
      showed significantly higher state anxiety (S-anxiety) levels vs those in Group A
      and controls (P=0.001); trait anxiety (T-anxiety) was significantly higher in
      Group B and controls vs Group A (P=0.001 and P=0.03). CONCLUSIONS: Our results
      confirm the literature data about musculoskeletal and visual disorders and, as
      for anxiety, seem to denote a higher relevance of factors related to labor
      organization vs VDT use per se.

PMID- 17213783
TI  - A pharmacoeconomic evaluation of oral triptans in the treatment of migraine in
      Italy.
AB  - AIM: The goal of this economic evaluation was to compare the cost-efficacy of
      oral triptans currently used in the treatment of migraine in Italy. METHODS: The
      cost analysis of drugs was conducted through a structured decision tree, built up
      taking into account the National Healthcare System perspective. Data on the
      clinical efficacy and tolerability of oral triptans were derived from a published
      meta-analysis of 53 randomized, controlled trials. Drug cost-allocation included
      either the oral triptans price and costs related to management of treatment
      associated chest and central nervous system (CNS) adverse events. Necessary
      resources for management of the unwanted events were identified by asking an
      experienced panel of experts how they would treat patients with triptan-related
      chest and CNS adverse events. To further improve the economic scenario and to
      allow a broader inference of pharmacoeconomic analysis, the number needed to
      treat (NNT) to attain 100 sustained pain free (SPF) patients, and 100 patients
      with SPF and no adverse events (SNAE) were also calculated. RESULTS: Study
      results show cost-effective differences among oral triptans. The best cost
      efficacy ratios were attained by almotriptan 12.5 mg and rizatriptan 5 mg, with
      18.47 Euro and 26.37 Euro respectively per patient successfully treated (SPF).
      Similarly, the NNT analysis favoured almotriptan, which requires 386 patients to
      attain 100 SPF patients, and 393 patients to attain 100 SNAE patients.
      Rizatriptan 10 mg resulted the closest competitor, requiring 395 and 457
      patients, respectively. CONCLUSIONS: On the basis of published data and within
      the limitations of this model analysis that included several assumptions, results
      suggest the economical advantage of almotriptan 12.5 mg among the oral triptans
      approved for the treatment of migraine in Italy. This evidence could drive
      selection of the most appropriate oral treatment for acute migraine attacks based
      on both individual patient's needs and cost-effective drugs.

PMID- 17213784
TI  - Osteoporosis in females prior to menopause: current concepts regarding
      definition, screening and management.
AB  - Few practice guidelines exist to guide the clinician to the diagnosis and
      management of osteoporosis in the premenopausal woman. Many clinical concerns
      exist due to the paucity of clinical research studies, while at the same time
      widespread screening has resulted in an increase number of premenopausal women
      having their bone mineral density measured. The major issue that has arisen is
      not therapy, but what is the definition of osteoporosis in premenopausal women.
      We have no specific definition, for thus it is very difficult to make and
      specific recommendation on therapy based on bone mineral density numbers alone.
      Concerns over the definition, screening and management of osteoporosis in
      premenopausal women are addressed in this review based on the most recent
      available clinical data and consensus reports.

PMID- 17213785
TI  - Hypolipidaemia is not always indicating liver dysfunction. A review of primary
      and secondary high density lipoprotein and low density lipoprotein deficiencies.
AB  - Hypolipidaemias can be either primary due to several genetic defects altering the
      serum concentration of lipoproteins, or secondary resulting from various
      disorders such as liver disease, malabsorption, malnutrition, malignancy,
      hyperthyroidism and immunoglobulin disorders. We present a review of the current
      knowledge regarding the various causes of hypolipidaemias. Our aim is to
      emphasize on the different mechanisms, apart from deranged liver synthetic
      function, that are responsible for unusually low levels of cholesterol and on the
      disorders that need to be considered during the investigation of hypolipidaemia.

PMID- 17213786
TI  - Pathogenesis, clinical findings and management of acute and chronic gout.
AB  - Gout is a chronic metabolic disease caused by a disorder of the purine metabolism
      leading to hyperuricaemia. It is determined by the deposition of monosodium urate
      crystals in joints and other tissues which causes an acute inflammatory response
      and can induce a permanent tissue damage which defines the urate chronic joint
      disease which is characterised by the appearance of ulceration of the joint
      cartilage, marginal osteophytosis, geodic and erosive lesions and chronic
      inflammation of synovial membrane. Gout and hyperuricaemia usually occur after
      the age of 30 years and more frequently in men. Hyperuricaemia is the result of
      an increased production of uric acid or its hypoexcretion by the kidneys, or
      both. In the pathogenesis of gout and hyperuricaemia are involved genetic and
      environmental factors; further, different pathologic condition such as
      glycogenosis, renal insufficiency, use of some drugs, are associated with gout.
      Treatment of acute gout includes colchicine, nonsteroidal anti-inflammatory drugs
      and glucocorticoids, whereas in the intercritical periods colchicine is effective
      for preventive purposes. Urate-lowering therapy with xanthine-oxidase inhibitors
      or uricosuric agents is indicate only in patients with more than two gout crisis
      per year, tophaceous deposits, uric acid nephrolithiasis, and interstitial renal
      disease, as asymptomatic hyperuricaemia does not requires any treatment but can
      be controlled with preventive dietetic measures and changes in lifestyle.

PMID- 17213787
TI  - Safety and efficacy of administering 0.2 mg of recombinant human TSH for two
      consecutive days as an adjuvant to therapy with low radioiodine doses in elderly
      out-patients with large nontoxic multinodular goiter.
AB  - AIM: The aim of this study was to evaluate the efficacy of recombinant human TSH
      (rhTSH) as an adjuvant to radioiodine therapy for nontoxic multinodular goiter
      (MNG) in elderly subjects. METHODS: Twelve elderly out-patients with large MNG
      (group 1) were studied. The effect of adjuvant rhTSH administration (0.2 mg i.m.
      on 2 consecutive days) before low-dose (131)I was compared with that of
      radioiodine alone in 8 out-patients matched for age and MNG volume (group 2). The
      follow-up period was similar in both groups. RESULTS: The number and severity of
      side-effects during the first month of treatment were similar in both groups. On
      final examination, the number of patients symptomatic for goiter was
      significantly lower in group 1 than in group 2 (P=0.03). In group 1, TSH levels
      peaked at 40.3+/-9.5 mU/L on day 3, from the baseline value of 0.5+/-0.1 mU/L
      (P<0.001). In group 2, baseline TSH was 0.4+/-0.1 mU/L. Although a marked
      increase in f-T3, f-T4 and Tg (P<0.001) was noted in both groups during the first
      2 weeks of treatment, peak values were much higher in group 1 than in group 2. On
      final examination, a slightly significant increase (P=0.01) in TSH levels from
      the baseline was noted in both groups (group 1: 1.2+/-0.2 mU/L; group 2: 1.4+/
      0.3 mU/L). The percentage of patients who did not need therapies to control TSH
      secretion at the last examination was higher in group 1 (83%) than in group 2
      (38%). Only in group 1, a significant reduction was noted in mean anterior
      posterior lobar width (31+/-1.7 mm) from the baseline value (24.5+/-1.7 mm,
      P=0.04). Thyroid volume was reduced from 78.1+/-11.7 mL to 49.4+/-13.4 mL
      (P=0.001) in group 1 and from 89.8+/-25.2 mL to 67.1+/-20.5 mL (P=0.04) in group
      2. Six months after (131)I therapy, slight changes in thyroid length and tracheal
      lumen were noted in both groups. CONCLUSIONS: This long-term controlled study
      demonstrates that 0.2 mg of rhTSH on 2 consecutive days increases the efficacy of
      ambulatory (131)I dosages in treating nontoxic MNG in elderly subjects. Adequate
      drug preparation generally prevents side-effects due to short-term but marked
      thyrotoxicosis that is aggravated by rhTSH administration. An increase in thyroid
      volume reduction seems to be the most important effect of rhTSH administered
      before (131)I.

PMID- 17213788
TI  - Growth hormone provocation tests and their prediction in the growth of children
      treated for acute lymphoblastic leukemia.
AB  - AIM: The aim of this study was to evaluate the positive predictive value of two
      growth hormone stimulation tests (insulin-induced hypoglycemia and clonidine) for
      stature below percentile 10 in patients treated for acute lymphoblastic leukemia
      in childhood. METHODS: The study population was a cohort of 30 patients (aged
      14.1+/-2.9 years; 20 male) treated for acute lymphoblastic leukemia during
      childhood and then examined after insulin-induced hypoglycemia (30 patients) and
      clonidine (16 patients) tests. The follow-up time was 7.7+/-2.8 years since
      treatment and 2.3+/-1.3 years after administration of the tests. RESULTS: In the
      last evaluation, 12 patients (40%) were below and 18 (60%) were above percentile
      10. The insulin-induced hypoglycemia test response was: 9 patients (30%) had
      growth hormone peak <5 ng/mL and 19 (63.3%) <7 ng/mL. The clonidine test response
      was: 7 patients had growth hormone peak <5 ng/mL and 8 (50%) <7 ng/mL. For
      stature below of the percentile 10, the positive predictive values of insulin
      induced hypoglycemia test (33%) and clonidine (28%) were low when growth hormone
      peak <5 ng/mL was considered; however, when growth hormone peak <7 ng/mL was
      considered, the positive predictive values were 83% and 50% for the insulin
      induced hypoglycemia and clonidine tests, respectively. CONCLUSIONS: In patients
      treated for acute lymphoblastic leukemia in childhood, the positive predictive
      values for statural deficit of both tests were low, except for the insulin
      induced hypoglycemia test when a growth hormone peak <7 ng/mL was considered.

PMID- 17213789
TI  - Clinical islet transplantation.
AB  - Achieving stable metabolic control in patients with type 1 diabetes mellitus
      (T1DM) is highly desirable and may contribute to delaying and/or preventing the
      development of secondary complications. Transplantation of pancreatic islets
      represents a viable option for the treatment of patients with unstable T1DM with
      frequent severe hypoglycemia and hypoglycemia unawareness. The benefits of the
      transplant include improvement of glycemic control, prevention of severe
      hypoglycemia and amelioration of quality of life. The success of future clinical
      trials will depend on the implementation of an integrated therapeutic approach
      combining strategies to maximize islet availability and engraftment with those
      aiming at safely modulating the recipients' immunity to afford long-term
      function. The steady progress of recent years in islet cell processing and
      patient management after transplantation justify great optimism for the years to
      come.

PMID- 17213790
TI  - Pituitary expansive adenoma. A report of a case and differential diagnosis.
AB  - Notwithstanding recent neuroendocrinological and neuroradiological findings,
      about 40% of carriers of pituitary adenoma still reach clinical observation and,
      consequently, the surgeon, in the stage of suffering from extrasellar extension
      to a varying degree, especially when the volumetric growth of the lesion is not
      accompanied by a state of endocrine dysfunction which could benefit early
      identification. Once established, the symptomatology could point us to the site
      of the expansive process but not supply indications regarding the histotype whose
      recognition, apart from instrumental investigation with radiography and
      scintigraphy, must be verified directly with craniotomy or transphenoidal access.
      Like all neoplastic conditions, the prognostic impact of exeresis is conditioned
      by the stage of the disease which for non-secreting pituitary adenomas, such as
      that encountered in the sixty-four-year-old woman observed by us, is about 70%.

PMID- 17213791
TI  - Intrathyroid parathyroid adenoma potentially mimicking a parathyroid carcinoma.

PMID- 17213792
TI  - Tadalafil and modifications in peak systolic velocity (Doppler spectrum dynamic
      analysis) in the cavernosal arteries of patients with type 2 diabetes after
      continuous tadalafil treatment.
AB  - AIM: In this study peak systolic velocity (PSV) was measured by penile duplex
      Doppler spectrum dynamic analysis in diabetic patients with erectile dysfunction
      (ED) administered continuous treatment with tadalafil for 3 months in a weekly
      regimen (Monday-Wednesday-Friday). Responses to the Structured Interview on
      Erectile Dysfunction (SIEDY) questionnaire and hormonal blood levels (LH,
      testosterone, prolactin) were studied before and after treatment. METHODS: The
      study sample was 20 diabetic patients (mean age 60 years; range 55-65) with
      organic vascular arterial ED at enrollment into the study. All patients were
      eligible for receiving tadalafil. Patients were randomly assigned to 2 different
      treatment groups according to a computer-generated list. The first random set of
      numbers was assigned to group A, the second to group B. Group A (n=10) received
      tadalafil 20 mg per os on demand for 3 months (Cialis, Lilly ICOS; London, UK).
      Group B (n=10) received tadalafil 20 mg per os on weekly fixed days (Monday
      Wednesday-Friday) for 3 months. All patients underwent duplex penile sonographic
      dynamic evaluation after intracavernosal injection of alprostadil 20 microg
      (Caverject, Pharmacia SpA; Milan, Italy); SIEDY questionnaire responses and
      changes in blood hormonal levels (LH, testosterone, prolactin) before and after
      treatment were compared. RESULTS: Increased PSV at 10 min and 20 min after
      alprostadil administration was found in 30% of Group A patients and in 60% of
      Group B patients. In 40% of Group B patients, the increase in PSV was so
      significant as to justify reclassification to a less severe diagnostic category
      (Benson classification) in vascular profile. No changes in hormonal levels after
      treatment were found in either group. Analysis of the questionnaires showed a
      more marked reduction in the global total scores in Group B, with a greater
      frequency and a clearer improvement in global scores. CONCLUSIONS: This study on
      a group of 20 patients with organic vascular arterial ED disclosed at least 2
      basic aspects: 1) a higher percentage of Group B patients (fixed-day treatment
      regimen) showed a greater improvement in PSV than the controls; 40% of these
      patients were reclassified according to the Benson classification; 2) within the
      context of a clinical study, monitoring and supportive care to increase the
      frequency and quality of sexual intercourse led to a resumption of and a greater
      interest in sexual activity. This finding cannot be explained by changes in
      hormonal levels; instead, there appeared a sort of effect placebo that the
      continuous therapy, like conventional treatment for other health reasons, had on
      the patient.

PMID- 17213793
TI  - Mono or bilateral inflammatory postmicrobial prostato-vesciculo-epididymitis:
      differences in semen parameters and reactive oxygen species production.
AB  - AIM: The aim of this study was to analyse possible differences in sperm
      characteristics (including seminal leukocyte concentration, number of
      spermiophagies, and sperm reactive oxygen species [ROS] production) between
      patients with monolateral and bilateral prostate-vesciculo-epididymitis (PVE).
      METHODS: Seventy-eight selected consecutively enrolled patients (mean age 34
      years, range 24-40) with chronic inflammatory postmicrobial PVE and 30 infertile
      (aged-matched) patients (control group) with inflammatory postmicrobial
      prostatitis underwent sperm analysis, including seminal leukocyte concentration,
      number of spermiophages, and ROS production. RESULTS: Sperm concentration and
      total sperm number were significantly lower in the patients with bilateral PVE
      than in those with monolateral PVE. The percentage of cases with oligozoospermia
      or hyperspermia was significantly higher among patients with bilateral PVE with
      than those with monolateral PVE. Although the remaining cytologic and
      physicochemical sperm characteristics and ROS production (both in 45% and 90%
      Percoll fractions) were not significantly different between the 2 PVE groups,
      both groups showed median and relative percentages of frequency of abnormal sperm
      characteristics worse than those in the control group. CONCLUSIONS: Although
      sperm abnormalities (including seminal leukocyte concentration, number of
      spermiophages, and ROS production) can distinguish patients with PVE from those
      with prostatitis alone, the abnormalities did not discriminate between unilateral
      and bilateral PVE. In diagnostic suspicion of PVE, didymo-epididymal and prostato
      vescicular ultrasonography can help discriminate monolateral from bilateral forms
      of PVE, and is a useful aid in the follow-up of these patients.

PMID- 17213794
TI  - Role of endocrine and inflammatory alterations in comorbid somatic diseases of
      post-traumatic stress disorder.
AB  - Since its first description in the Diagnostic and Statistical Manual for Mental
      Disorders, post-traumatic stress disorder (PTSD) has been characterized as a
      disorder of altered affective functioning which causes tremendous distress. In
      addition, it has been recognized that PTSD is not only accompanied by ''poor
      health'' but also by a number of specific and non-specific ''somatic''
      pathologies, such as cardiovascular, autoimmune and physical complaints/chronic
      pain. It has been hypothesized that alterations of the hypothalamic-pituitary
      adrenal (HPA) axis, the sympathetic-adrenal-medullary (SAM) and the immune system
      may mediate or facilitate these somatic conditions. The aims of this review are
      to summarize studies that report altered somatic functioning in PTSD and to
      review how endocrine and immune function differentially affect PTSD-related
      somatic malfunction. It is hypothesized that alterations of HPA axis and SAM
      system permit disinhibition of inflammatory mechanisms, which in turn foster the
      development of somatic diseases as well as self-reported physical complaints.

PMID- 17213795
TI  - Polyglandular autoimmune endocrine insufficiency complicated by severe
      osteoporosis.
AB  - In literature different cases of polyglandular autoimmune type II syndrome (PGA
      II) are reported, where Addison's disease is associated with gonadal
      insufficiency. The lack in the production of sexual steroids causes a severe
      postmenopausal osteoporosis. The case we report is related to a 38-year-old woman
      we met in 1988 and who was suffering from deep asthenia, cramps, cutaneous
      hyperpigmentation, nausea, vomiting, abdominal pain, weight loss and hypotension.
      The biochemical data were indicative for autoimmune adrenal failure. Between 1988
      and 1997 the patient developed a progressive insufficiency of other endocrine
      glands, leading to the classic feature of PGA II. In 1998, this clinical status
      was complicated by a severe osteoporosis. We thought that the sudden decrease in
      the bony mineral density was due to the lack of the protective role played by
      adrenal gland androgens in postmenopausal osteoporosis. They would directly act
      on the bony tissue, independently from oestrogens peripheral conversion, thus
      producing a stimulant effect on the bone formation. A new therapeutical approach,
      in case of osteoporosis, is today represented by DHEA replacement therapy in
      women showing low hormone levels.

PMID- 17213796
TI  - Immunocytochemical evidence that rod-connected horizontal cell axon terminals
      remodel in response to experimental retinal detachment in the cat.
AB  - PURPOSE: Cats have two types of horizontal cell (HC); one is axon-bearing (B
      type), the other is axonless (A-type). We have previously described neurite
      sprouting from HCs in response to experimental retinal detachment. Here we sought
      to determine whether one or both types elaborate these outgrowths. METHODS:
      Sections as well as wholemounts of retinas detached for 3, 7 and 28 days together
      with control retinas were double or triple labeled with antibodies to the calcium
      binding proteins calretinin and calbindin, to the synaptic vesicle-associated
      membrane protein 2 (VAMP2), and to the 70 and 200 kDa subunits of the
      neurofilament protein. Digital immunofluorescence images were collected by both
      confocal and two-photon microscopy. RESULTS: In control retina, both HC types
      label with antibodies to calretinin and calbindin D, but only the A-type also
      intensely labels with the neurofilament protein antibody. After 3, 7 and 28 days
      of detachment, these staining patterns persist, but there is a moderate
      upregulation of neurofilament protein in the B-type cell. In the detached retina,
      HC processes sprout neurites that appear most commonly as a loose array of fine
      beaded processes rising from the outer plexiform layer (OPL) into the outer
      nuclear layer (ONL), or, especially at 28 days, as stout unbranching processes
      that often cross the ONL en route to the subretinal space where some expand and
      arborize. Both types are strongly calretinin-positive while being somewhat less
      positive for antibodies to calbindin D and neurofilament protein. Moreover, they
      all arise from similarly labeled processes in the distal-most domain of the OPL
      where the narrowly stratified field of axon terminal boutons of the B-type HC
      normally innervates rod spherules, two to three thousand per cell. Our data
      indicate that the HC sprouts apparently arise specifically from the axon terminal
      of the B-type cell since outgrowths were never seen arising from either type of
      HC perikaryon or from processes identifiable as A-type dendrites. CONCLUSIONS:
      The data described here point to the specific remodeling of the rod-connected
      axon terminals of the B-type cell through neurite outgrowth. Rods respond to
      detachment by withdrawing synaptic terminals from the OPL while cones do not.
      Those HC outgrowths that terminate within the ONL appear to retain their
      connection with the retracted terminals. Others apparently have lost their
      presynaptic targets and cross the ONL in association with hypertrophied Muller
      cell processes.

PMID- 17213797
TI  - An association between BPDE-like DNA adduct levels and P53 gene mutation in
      pterygium.
AB  - PURPOSE: A previous report of ours noted that not only p53 protein
      overexpression, but also p53 gene mutation. were indeed detected in pterygium.
      BaP 7,8-diol 9,10-epoxide (BPDE), an ultimate metabolite of BaP, attacks
      deoxyguanosine to form a BPDE-N2-dG adduct resulting in p53 mutations. The
      relationship between BPDE-like DNA adduct levels and abnormal p53 has not been
      clear in pterygium. Therefore, BPDE-like DNA adduct, p53 protein expression and
      p53 gene mutation were examined in this study to provide more molecular evidence
      to understand the cause of p53 gene mutation in pterygium. METHODS: In this
      study, immunohistochemical staining, using a monoclonal antibody (DO7) against
      p53 and a polyclonal antibody against BPDE-like DNA adducts, was performed on 73
      pterygial specimens. DNA samples for p53 mutation analysis were extracted from
      epithelial cells and then subjected to DNA sequencing for the determination of
      mutations in exons 4, 5, 6, 7, and 8 of the p53 gene. RESULTS: BPDE-like DNA
      adducts were detected in 36.1% (26/73) pterygium samples. No correlation between
      adduct levels and p53 protein expression was found in these samples.
      Additionally, the p53 gene mutation and p53 mutation pattern also did not
      correlate with BPDE-like DNA adduct levels. CONCLUSIONS: Our data provides
      evidence that BPDE-like DNA adducts are indeed detected in pterygium samples, and
      they are only minor contributors to the abnormal p53 gene.

PMID- 17213798
TI  - Gene expression profiling in embryonic mouse lenses.
AB  - PURPOSE: In this study, we used laser capture microdissection (LCM) and
      microarray hybridization technology to compare the gene expression profiles of
      mouse embryonic days 10 and 12 lenses (E10 and E12). METHODS: Lens cells of
      C57/BL6 mouse embryos at E10 and E12 were harvested using the PixCell II LCM
      System. Total RNA was extracted, amplified, labeled, and hybridized to the 430
      2.0 mouse chip (Affymetrix) according to the manufacturer's instructions. Data
      extracted from the images were analyzed using different software programs.
      Regulated expression of selected genes was confirmed by real-time PCR (RT-PCR).
      RESULTS: Analysis of the microarray data from E10 and E12 lenses identified 1,573
      genes that showed a two fold or greater change in expression level. Among these
      1,573 genes, 956 genes were downregulated and 617 were upregulated in E12 lenses.
      In addition to the upregulated expression of beta- and gamma-crystallin genes,
      genes that regulate the cell cycle showed significant changes of gene expression
      during the E10 (lens pit) to E12 (primary fiber cell induction) time period.
      Genes involved in insulin-like growth factor (IGF) signaling and Wnt (a family of
      secreted glycoproteins related to the Drosophila segment polarity gene, wingless,
      and to the proto-oncogene, int-1) signaling were also differentially regulated.
      In particular, positive regulators of Wnt signaling were downregulated and
      negative regulators were upregulated, indicating that modulation of Wnt signaling
      is important for normal lens morphogenesis. CONCLUSIONS: Our results provide new
      information about differential regulation of gene expression during early lens
      development. Analysis of global gene expression profiles in embryonic mouse
      lenses has allowed us to identify several molecular pathways that are
      differentially regulated during early lens development.

PMID- 17213799
TI  - Retinoids restore normal cyclic nucleotide sensitivity of mutant ion channels
      associated with cone dystrophy.
AB  - PURPOSE: To determine whether inhibition of cyclic nucleotide-gated (CNG) ion
      channels by retinoids might be useful in treating degenerative retinal diseases
      in which either the CNG channels are hypersensitive to 3',5'-cyclic guanosine
      monophosphate (cGMP) or the photoreceptor cGMP concentration is elevated.
      METHODS: Patch clamp (electrophysiological) methods were used to measure
      activation by cGMP of wild-type human cone (hCNGA3), mutant cone (hCNGA3-N471S),
      and wild-type bovine rod (bCNGA1) CNG channels heterologously expressed in
      Xenopus oocytes. Cyclic GMP-activated currents were measured in excised, inside
      out membrane patches before and after treatment with either all-trans retinal
      (ATR) or all-trans C22 aldehyde, which is too long to fit into the chromophore
      binding pocket of opsin and therefore cannot activate the visual transduction
      cascade. RESULTS: At physiological cGMP concentrations, 150 nM ATR reduced the
      open probability of the mutant cone CNG channel by reducing its apparent cGMP
      affinity to that of the normal cone channel. Furthermore, all-trans C22 aldehyde
      similarly inhibited the mutant cone channel as well as normal rod and cone CNG
      channels. CONCLUSIONS: Our results raise the possibility that retinoids, such as
      all-trans C22 aldehyde, that inhibit CNG channels without affecting the
      transduction cascade, may be useful in treating degenerative retinal diseases in
      which either the cGMP concentration is elevated or the CNG channels are
      hypersensitive to cGMP.

PMID- 17213800
TI  - Tool from ancient pharmacopoeia prevents vision loss.
AB  - PURPOSE: Bear bile has been used in Asia for over 3,000 years to treat visual
      disorders, yet its therapeutic potential remains unexplored in Western vision
      research. The purpose of this study was to test whether treatment of mice
      undergoing retinal degeneration with tauroursodeoxycholic acid (TUDCA), a primary
      constituent of bear bile, alters the course of degeneration. METHODS: Two retinal
      degeneration models were tested: the rd10 mouse, which has a point mutation in
      the gene encoding the beta subunit of rod phosphodiesterase, and light induced
      retinal damage (LIRD). For LIRD studies, albino Balb/C adult mice were
      subcutaneously injected with TUDCA (500 mg/kg body weight) or vehicle (0.15 M
      NaHCO(3)). Sixteen h later, each mouse received repeat injections. Half of each
      treatment group was then placed in bright light (10,000 lux) or dim light (200
      lux) for seven h. At the end of exposure, animals were transferred to their
      regular housing. Electroretinograms (ERGs) were assessed 24 h later, mice
      sacrificed, eyes embedded in paraffin and sectioned, and retina sections assayed
      for morphology and apoptosis by TUNEL and anti-active caspase-3 immunoreactivity
      via fluorescent confocal microscopy. A subset of mice were sacrificed 8 and 15
      days after exposure and retina sections analyzed for morphology and apoptosis.
      For rd10 studies, mice were injected subcutaneously with TUDCA or vehicle at
      postnatal (P) days 6, 9, 12, and 15. At p18, ERGs were recorded, mice were
      euthanized and eyes were harvested, fixed, and processed. Retinal sections were
      stained (toluidine blue), and retinal cell layers morphometrically analyzed by
      light microscopy. Consecutive sections were analyzed for apopotosis as above.
      RESULTS: By every measure, TUDCA greatly slowed retinal degeneration in LIRD and
      rd10 mice. ERG a-wave and b-wave amplitudes were greater in mice treated with
      TUDCA compared to those treated with vehicle. Retinas of TUDCA-treated mice had
      thicker outer nuclear layers, more photoreceptor cells, and more fully-developed
      photoreceptor outer segments. Finally, TUDCA treatments dramatically suppressed
      signs of apoptosis in both models. CONCLUSIONS: Systemic injection of TUDCA, a
      primary constituent of bear bile, profoundly suppressed apoptosis and preserved
      function and morphology of photoreceptor cells in two disparate mouse models of
      retinal degeneration. It may be that bear bile has endured so long in Asian
      pharmacopeias due to efficacy resulting from this anti-apoptotic and
      neuroprotective activity of TUDCA. These results also indicate that a systematic,
      clinical assessment of TUDCA may be warranted.

PMID- 17213801
TI  - A gene transcription signature of the Akt/mTOR pathway in clinical breast tumors.
AB  - The Akt pathway is commonly deregulated in many cancers. Clinical trials are
      currently underway to test the effectiveness of breast cancer treatment by
      inhibition of various Akt pathway intermediates. A set of genes induced by Akt in
      a transgenic mouse model, a subset of which were sensitive to mammalian target of
      rapamycin (mTOR) inhibitor RAD001, was examined in five public gene expression
      profile data sets of clinical breast tumor specimens (representing >1000
      different samples in all). In each of the clinical data sets, the Akt mouse model
      genes as a group were significantly overexpressed in human tumors having high
      levels of AKT1 mRNA. The subset of genes both upregulated by Akt and dependent on
      mTOR activity were associated with estrogen receptor-negative status, higher
      grade, increasing tumor size and poor prognosis in multiple patient cohorts;
      these associations were either not present or not as strong for the Akt-induced,
      mTOR-independent genes or for AKT1 expression alone. The genes shown here to be
      relevant to Akt-mTOR both experimentally and pathologically have the potential
      for use in a molecular diagnostic to determine which patients should receive mTOR
      antagonist treatment.

PMID- 17213803
TI  - Acquired resistance to reoviral oncolysis in Ras-transformed fibrosarcoma cells.
AB  - Reovirus shows considerable potential as an oncolytic agent for Ras-activated
      tumors and is currently in clinical trials. Here we ask whether such tumor cell
      lines can acquire resistance to reoviral oncolysis. We challenged human HT1080
      fibrosarcoma cells that carry a Ras mutation by prolonged exposure to reovirus,
      thereby yielding highly virus-resistant HTR1 cells. These cells are persistently
      infected with reovirus, exhibit high Ras activity and retain the original Ras
      gene mutation, showing that resistance to reovirus can be displayed in cells with
      active Ras. The HTR1 cells also exhibit reduced cellular cathepsin B activity,
      which normally contributes to viral entry and activation. Persistently infected
      HTR1 cells were not tumorigenic in vivo, whereas immunologically cured virus-free
      HTR1 cells were highly tumorigenic. Thus, acquisition of resistance to reovirus
      may constrain therapeutic strategies. To determine whether reoviral resistance is
      associated with a general reduction in apoptotic potential, we challenged the
      HTR1 cells with apoptotic inducers and E1B-defective adenovirus, resulting in
      significant apoptosis and cell death following both approaches. Therefore, even
      if resistance to reoviral oncolysis should arise in tumor cells in vivo, other
      therapeutic strategies may nevertheless remain effective.

PMID- 17213802
TI  - Transcriptomal profiling of the cellular transformation induced by Rho subfamily
      GTPases.
AB  - We have used microarray technology to identify the transcriptional targets of Rho
      subfamily guanosine 5'-triphosphate (GTP)ases in NIH3T3 cells. This analysis
      indicated that murine fibroblasts transformed by these proteins show similar
      transcriptomal profiles. Functional annotation of the regulated genes indicate
      that Rho subfamily GTPases target a wide spectrum of functions, although loci
      encoding proteins linked to proliferation and DNA synthesis/transcription are
      upregulated preferentially. Rho proteins promote four main networks of
      interacting proteins nucleated around E2F, c-Jun, c-Myc and p53. Of those, E2F, c
      Jun and c-Myc are essential for the maintenance of cell transformation.
      Inhibition of Rock, one of the main Rho GTPase targets, leads to small changes in
      the transcriptome of Rho-transformed cells. Rock inhibition decreases c-myc gene
      expression without affecting the E2F and c-Jun pathways. Loss-of-function studies
      demonstrate that c-Myc is important for the blockage of cell-contact inhibition
      rather than for promoting the proliferation of Rho-transformed cells. However, c
      Myc overexpression does not bypass the inhibition of cell transformation induced
      by Rock blockage, indicating that c-Myc is essential, but not sufficient, for
      Rock-dependent transformation. These results reveal the complexity of the genetic
      program orchestrated by the Rho subfamily and pinpoint protein networks that
      mediate different aspects of the malignant phenotype of Rho-transformed cells.

PMID- 17213804
TI  - NF-kappaB inhibition sensitizes to starvation-induced cell death in high-risk
      myelodysplastic syndrome and acute myeloid leukemia.
AB  - CD34(+) bone marrow blasts from high-risk myelodysplastic syndrome (MDS) patients
      as well as MDS patient-derived cell lines (P39 and MOLM13) constitutively
      activate the nuclear factor-kappaB (NF-kappaB) pathway and undergo apoptosis when
      NF-kappaB is inhibited. Here, we show that the combination of conventional
      chemotherapeutic agents (daunorubicin, mitoxantrone, 5-azacytidine or
      camptothecin) with the NF-kappaB inhibitor BAY11-7082 did not yield a synergistic
      cytotoxicity. In contrast, BAY11-7082 (which targets the NF-kappaB-activating I
      kappaB kinase (IKK) complex) or knockdown of essential components of the NF
      kappaB system (such as the IKK1 and IKK2 subunits of the IKK complex and the p65
      subunit of NF-kappaB), by small interfering RNAs sensitized MDS cell lines to
      starvation-induced apoptosis. The combination of BAY11-7082 and nutrient
      depletion synergistically killed the acute myeloid leukemia (AML) cell line U937
      as well as primary CD34(+) bone marrow blasts from AML and high-risk MDS
      patients. The synergistic killing by BAY11-7082, combined with nutrient
      depletion, led to cell death accompanied by all hallmarks of apoptosis, including
      an early loss of the mitochondrial transmembrane potential, the release of
      cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, activation of
      caspase-3, phosphatidylserine exposure on the plasma membrane surface and nuclear
      chromatin condensation. Transmission electron microscopy revealed the presence of
      numerous autophagic vacuoles in the cytoplasm before cells underwent nuclear
      apoptosis. Nonetheless, cell death was neither inhibited by the pan-caspase
      inhibitor z-VAD-fmk nor by knockdown of AIF or of essential components of the
      autophagy pathway (ATG5, ATG6/Beclin-1, ATG10, ATG12). In contrast, external
      supply of glucose, insulin or insulin-like growth factor-I could retard the cell
      death induced by BAY11-7082 combined with starvation. These results suggest that
      in MDS cells, NF-kappaB inhibition can precipitate a bioenergetic crisis that
      leads to an autophagic stress response followed by apoptotic cell death.

PMID- 17213805
TI  - TLX1/HOX11-induced hematopoietic differentiation blockade.
AB  - Aberrant expression of the human homeobox-containing proto-oncogene TLX1/HOX11
      inhibits hematopoietic differentiation programs in a number of murine model
      systems. Here, we report the establishment of a murine erythroid progenitor cell
      line, iEBHX1S-4, developmentally arrested by regulatable TLX1 expression.
      Extinction of TLX1 expression released the iEBHX1S-4 differentiation block,
      allowing erythropoietin-dependent acquisition of erythroid markers and hemoglobin
      synthesis. Coordinated activation of erythroid transcriptional networks
      integrated by the acetyltransferase co-activator CREB-binding protein (CBP) was
      suggested by bioinformatic analysis of the upstream regulatory regions of several
      conditionally induced iEBHX1S-4 gene sets. In accord with this notion, CBP
      associated acetylation of GATA-1, an essential regulator of erythroid
      differentiation, increased concomitantly with TLX1 downregulation.
      Coimmunoprecipitation experiments and glutathione-S-transferase pull-down assays
      revealed that TLX1 directly binds to CBP, and confocal laser microscopy
      demonstrated that the two proteins partially colocalize at intranuclear sites in
      iEBHX1S-4 cells. Notably, the distribution of CBP in conditionally blocked
      iEBHX1S-4 cells partially overlapped with chromatin marked by a repressive
      histone methylation pattern, and downregulation of TLX1 coincided with exit of
      CBP from these heterochromatic regions. Thus, we propose that TLX1-mediated
      differentiation arrest may be achieved in part through a mechanism that involves
      redirection of CBP and/or its sequestration in repressive chromatin domains.

PMID- 17213807
TI  - Targeting SPARC expression decreases glioma cellular survival and invasion
      associated with reduced activities of FAK and ILK kinases.
AB  - Secreted protein acidic and rich in cysteine (SPARC) is an extracellular
      glycoprotein expressed in several solid cancers, including malignant gliomas,
      upon adoption of metastatic or invasive behaviors. SPARC expression in glioma
      cells promotes invasion and survival under stress, the latter process dependent
      on SPARC activation of AKT. Here we demonstrate that downregulation of SPARC
      expression with short interfering RNA (siRNA) in glioma cells decreased tumor
      cell survival and invasion. SPARC siRNA reduced the activating phosphorylation of
      AKT and two cytoplasmic kinases, focal adhesion kinase (FAK) and integrin-linked
      kinase (ILK). We determined the contributions of FAK and ILK to SPARC effects
      using SPARC protein and cell lines engineered to overexpress SPARC. SPARC
      activated FAK and ILK in glioma cells previously characterized as responsive to
      SPARC. Downregulation of either FAK or ILK expression inhibited SPARC-mediated
      AKT phosphorylation, and targeting both FAK and ILK attenuated AKT activation
      more potently than targeting either FAK or ILK alone. Decreased SPARC-mediated
      AKT activation correlated with a reduction in SPARC-dependent invasion and
      survival upon the downregulation of FAK and/or ILK expression. These data further
      demonstrate the role of SPARC in glioma tumor progression through the activation
      of intracellular kinases that may provide novel therapeutic targets for advanced
      cancers.

PMID- 17213806
TI  - CLCP1 interacts with semaphorin 4B and regulates motility of lung cancer cells.
AB  - We previously established a highly metastatic subline, LNM35, from the NCI-H460
      lung cancer cell line, and demonstrated upregulation of a novel gene, CLCP1 (CUB,
      LCCL-homology, coagulation factor V/VIII homology domains protein), in LNM35 and
      lung cancer specimens. In this study, we focused on the potential roles of that
      gene in cancer metastasis. First, we established stable LNM35 RNAi clones, in
      which CLCP1 expression was suppressed by RNAi, and found that their motility was
      significantly reduced, although growth rates were not changed. Next, in vitro
      selection of a phage display library demonstrated that a phage clone displaying a
      peptide similar to a sequence within the Sema domain of semaphorin 4B (SEMA4B)
      interacted with LNM35. Immunoprecipitation experiments confirmed interaction of
      CLCP1 with SEMA4B, regulation of CLCP1 protein by ubiquitination and proteasome
      degradation enhanced in the presence of SEMA4B. These results are the first to
      indicate that CLCP1 plays a role in cell motility, whereas they also showed that
      at least one of its ligands is SEMA4B and that their interaction mediates
      proteasome degradation by CLCP1. Although the physiological role of the
      interaction between CLCP1 and SEMA4B remains to be investigated, this novel gene
      may become a target of therapy to inhibit metastasis of lung cancers.

PMID- 17213808
TI  - HOXA1-stimulated oncogenicity is mediated by selective upregulation of components
      of the p44/42 MAP kinase pathway in human mammary carcinoma cells.
AB  - Expression of homeobox A1 (HOXA1) results in oncogenic transformation of
      immortalized human mammary epithelial cells with aggressive tumor formation in
      vivo. However, the mechanisms by which HOXA1 mediates oncogenic transformation is
      not well defined. To identify molecules that could potentially be involved in
      HOXA1-mediated oncogenic transformation, microarray analysis was utilized to
      characterize and compare the gene expression pattern in response to forced
      expression or depletion of HOXA1 in human mammary carcinoma cells. Gene
      expression profiling identified that genes involved in the p44/42 mitogen
      activated protein (MAP) kinase activation pathway (GRB2, MAP kinase kinase (MEK1)
      and SDFR1) or p44/42 MAP kinase-regulated genes (IER3, EPAS1, PCNA and catalase)
      are downstream expression targets of HOXA1. Forced expression of HOXA1 increased
      GRB2 and MEK1 mRNA and protein expression and increased p44/42 MAP kinase
      phosphorylation, activity and Elk-1-mediated transcription. Use of a MEK1
      inhibitor demonstrated that increased p44/42 MAP kinase activity is required for
      the HOXA1-mediated increase in cell proliferation, survival, oncogenicity and
      oncogenic transformation. Thus, modulation of the p44/42 MAP kinase pathway is
      one mechanism by which HOXA1 mediates oncogenic transformation of the human
      mammary epithelial cell.

PMID- 17213809
TI  - Identification and functional signature of genes regulated by structurally
      different ABL kinase inhibitors.
AB  - Dasatinib is an ATP-competitive, multi-targeted SRC and ABL kinase inhibitor that
      can bind BCR-ABL in both the active and inactive conformations. From a clinical
      standpoint, dasatinib is particularly attractive because it has been shown to
      induce hematologic and cytogenetic responses in imatinib-resistant chronic
      myeloid leukemia patients. The fact because the combination of imatinib and
      dasatinib shows the additive/synergistic growth inhibition on wild-type p210 BCR
      ABL-expressing cells, we reasoned that these ABL kinase inhibitors might induce
      the different molecular pathways. To address this question, we used DNA
      microarrays to identify genes whose transcription was altered by imatinib and
      dasatinib. K562 cells were cultured with imatinib or dasatinib for 16 h, and gene
      expression data were obtained from three independent microarray hybridizations.
      Almost all of the imatinib- and dasatinib-responsive genes appeared to be
      similarly increased or decreased in K562 cells; however, small subsets of genes
      were identified as selectively altered expression by either imatinib or
      dasatinib. The distinct genes that are selectively modulated by dasatinib are
      cyclin-dependent kinase 2 (CDK2) and CDK8, which had a maximal reduction of <5
      fold in microarray screen. To assess the functional importance of dasatinib
      regulated genes, we used RNA interference to determine whether reduction of CDK2
      and CDK8 affected the growth inhibition. K562 and TF-1BCR-ABL cells, pretreated
      with CDK2 or CDK8 small interfering RNA, showed additive growth inhibition with
      imatinib, but not with dasatinib. These findings demonstrate that the
      additive/synergistic growth inhibition by imatinib and dasatinib may be mediated
      in part by CDK2 and CDK8.

PMID- 17213811
TI  - DNA methylation and histone modification regulate silencing of epithelial cell
      adhesion molecule for tumor invasion and progression.
AB  - Epithelial cell adhesion molecule (Ep-CAM) is believed to have a critical role in
      carcinogenesis and cell proliferation. However, the association of Ep-CAM with
      cancer invasion and progression is less clear. We found that Ep-CAM was highly
      expressed on low-invasive cells compared with highly invasive cells. Forced
      expression of Ep-CAM decreased cancer invasiveness, and silencing Ep-CAM
      expression elevated cancer invasiveness. Ep-CAM expression was associated with
      promoter methylation. Treatment with a demethylating agent, and/or the histone
      deacetylase inhibitor reactivated Ep-CAM expression in Ep-CAM-negative cells and
      inhibited cancer invasiveness. Using a promoter-reporter construct, we
      demonstrated methylation of the promoter fragment drive Ep-CAM-silenced
      transcription. Additionally, silenced Ep-CAM gene in cancer cells was enriched
      for hypermethylated histone 3 lysine 9. When unmethylated and active, this
      promoter was associated with acetylated histone 3 lysine 9. Furthermore, we
      observed an increased association of Ep-CAM promoter with repression components
      as tumor invasiveness increased. In cancer tissues, Ep-CAM expression
      significantly correlated with tumor progression and associated with promoter
      methylation. Our data support the idea that modulation of Ep-CAM plays a pivotal
      role in tumor invasion and progression. Moreover, aberrant DNA methylation of Ep
      CAM is implicated in enhancing invasive/metastatic proclivity of tumors.

PMID- 17213810
TI  - Epigenetic patterns of the retinoic acid receptor beta2 promoter in retinoic acid
      resistant thyroid cancer cells.
AB  - Treatment with retinoic acid (RA) is effective to restore radioactive iodine
      uptake in metastases of a small fraction of thyroid cancer patients. In order to
      find predictive markers of response, we took advantage of two thyroid cancer cell
      lines, FTC133 and FTC238, with low RA-receptor (RAR)beta expression but differing
      in their response to RA. We report that in both cell lines, RA signalling
      pathways are functional, as transactivation of an exogenous RARbeta2 promoter is
      effective in the presence of pharmacological concentrations of all-trans RA, and
      enhanced in RA-resistant FTC238 cells after ectopical expression of RARbeta,
      suggesting a defective endogenous RARbeta2 promoter in these cells. Further
      analyses show that whereas the RARbeta2 promoter is in an unmethylated permissive
      status in both FTC133 and FTC238 cells, it failed to be associated with
      acetylated forms of histones H3 or H4 in FTC238 cells upon RA treatment.
      Incubation with a histone deacetylase inhibitor, alone or in combination with RA,
      restored histone acetylation levels and reactivated RARbeta and differentiation
      marker Na+/I- symporter gene expression. Thus, histone modification patterns may
      explain RA-refractoriness in differentiated thyroid cancer patients and suggest a
      potential benefit of combined transcriptional and differentiation therapies.

PMID- 17213812
TI  - A short N-terminal sequence of PTEN controls cytoplasmic localization and is
      required for suppression of cell growth.
AB  - Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is an important
      negative regulator of cell growth and a tumor suppressor. Its growth-attenuating
      activity is based on the dephosphorylation of phosphatidylinositol 3,4,5
      trisphosphate (PIP3), an essential second messenger for the phosphoinositide 3
      kinase/Akt signaling pathway. This activity may require localization of PTEN to
      cytoplasmic membranes. Yet PTEN can also localize to the cell nucleus where its
      functions remain unclear. Here we present data that define a short sequence in
      the N-terminal region of PTEN required for cytoplasmic localization. We will
      refer to this sequence as cytoplasmic localization signal (CLS). It could
      function as a non-canonical signal for nuclear export or as a cytoplasmic
      retention signal of PTEN. Mutations within the CLS induce nuclear localization
      and impair growth suppressive activities of PTEN while preserving lipid
      phosphatase activity. We propose that nuclear localization of PTEN is not
      compatible with plasma membrane-targeted growth suppressive functions of PTEN.

PMID- 17213813
TI  - Disparity of histone deacetylase inhibition on repair of radiation-induced DNA
      damage on euchromatin and constitutive heterochromatin compartments.
AB  - Epigenetic regulation of chromatin structure is central to the process of DNA
      repair. A well-characterized epigenetic feature is the dynamic phosphorylation of
      the histone H2AX (gammaH2AX) and mobilization of double strand break (DSB)
      recognition and repair factors to the site. How chromatin structure is altered in
      response to DNA damage and how such alterations influence DSB repair mechanisms
      are currently relevant issues. Despite the clear link between histone
      deacetylases (HDACs) and radiosensitivity, how histone hyperacetylation influence
      DSB repair remains poorly understood. We have determined the structure of
      chromatin is a major factor determining radiosensitivity and repair in human
      cells. Trichostatin A (TSA) enhances radiosensitivity with dose modification
      factors of 1.2 and 1.9 at 0.2 and 1 microM, respectively. Cells treated with TSA
      causing hyperacetylation and remodelling on euchromatic alleles coexist with
      gammaH2AX accumulation in radiosensitized cells. Formation of gammaH2AX on
      heterochromatin was significantly reduced even when cells were treated with TSA,
      suggesting that chromatin structure and histone hyperacetylation are pronounced
      features of radiation sensitivity and repair in euchromatic regions.

PMID- 17213814
TI  - Analysis of gene expression identifies PLAB as a mediator of the apoptotic
      activity of fenretinide in human ovarian cancer cells.
AB  - Fenretinide (4-HPR) is a synthetic retinoid with antitumor activity, which
      induces apoptosis in cancer cell lines of different histotypes. To identify genes
      contributing to its apoptotic activity in ovarian cancer cells, we monitored, by
      cDNA arrays, gene expression changes after 4-HPR exposure in A2780, a human
      ovarian carcinoma cell line sensitive to the retinoid. Among the differentially
      expressed transcripts, PLAcental Bone morphogenetic protein (PLAB), a
      proapoptotic gene, was the most highly induced. In a panel of ovarian carcinoma
      cell lines with different 4-HPR sensitivities, PLAB upregulation was associated
      with cellular response to 4-HPR, its overexpression increased basal apoptosis and
      its silencing by small interfering RNA decreased the ability of 4-HPR to induce
      apoptosis. PLAB induction by 4-HPR was p53- and EGR-1 independent and was
      regulated, at least in part, by increased stability of PLAB mRNA. PLAB up
      modulation by 4-HPR also occurred in vivo: in ascitic cells collected from
      patients with ovarian cancer before and after 4-HPR treatment, PLAB was
      upmodulated in 2/4 patients. Our results in certain ovarian cancer cell lines
      indicate a role for PLAB as a mediator of 4-HPR-induced apoptosis. The
      correlation of increased PLAB in vivo with antitumor activity remains to be
      established.

PMID- 17213815
TI  - Tumor promoting properties of the ETS protein MEF in ovarian cancer.
AB  - We have previously shown that MEF (myeloid ELF1-like factor, also known as ELF4)
      functions as a transcriptional activator of the interleukin (IL)-8, perforin,
      granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-3 genes in
      hematopoietic cells. MEF is also expressed in non-hematopoietic tissues including
      certain ovarian cancer cells. To define the function of MEF in these cells, we
      examined primary human ovarian epithelial tumors and found that MEF is expressed
      in a significant proportion of ovarian carcinomas, and in the CAOV3 and SKOV3
      ovarian cancer cell lines, but not in normal ovarian surface epithelium.
      Manipulating MEF levels in these cell lines altered their behavior; reducing MEF
      levels, using short hairpin RNA expressing vectors, significantly inhibited the
      proliferation of SKOV3 and CAOV3 cells in culture, and impaired the anchorage
      independent growth of CAOV3 cells. Overexpression of MEF in SKOV3 cells (via
      retroviral transduction) significantly increased their growth rate, enhanced
      colony formation in soft agar and promoted tumor formation in nude mice. The
      oncogenic activity of MEF was further shown by the ability of MEF to transform
      NIH3T3 cells, and induce their tumor formation in nude mice. MEF is an important
      regulator of the tumorigenic properties of ovarian cancer cells and could be used
      a therapeutic target in ovarian cancer.

PMID- 17213816
TI  - YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF
      kappaB signaling to HIF-1alpha accumulation during hypoxia.
AB  - Hypoxia-inducible factor 1 (HIF-1), a transcription factor that is critical for
      tumor adaptation to microenvironmental stimuli, represents an attractive
      chemotherapeutic target. YC-1 is a novel antitumor agent that inhibits HIF-1
      through previously unexplained mechanisms. In the present study, YC-1 was found
      to prevent HIF-1alpha and HIF-1beta accumulation in response to hypoxia or
      mitogen treatment in PC-3 prostate cancer cells. Neither HIF-1alpha protein half
      life nor mRNA level was affected by YC-1. However, YC-1 was found to suppress the
      PI3K/Akt/mTOR/4E-BP pathway, which serves to regulate HIF-1alpha expression at
      the translational step. We demonstrated that YC-1 also inhibited hypoxia-induced
      activation of nuclear factor (NF)-kappaB, a downstream target of Akt. Two
      modulators of the Akt/NF-kappaB pathway, caffeic acid phenethyl ester and
      evodiamine, were observed to decrease HIF-1alpha expression. Additionally,
      overexpression of NF-kappaB partly reversed the ability of wortmannin to inhibit
      HIF-1alpha-dependent transcriptional activity, suggesting that NF-kappaB
      contributes to Akt-mediated HIF-1alpha accumulation during hypoxia. Overall, we
      identify a potential molecular mechanism whereby YC-1 serves to reduce HIF-1
      expression.

PMID- 17213817
TI  - Selective inhibition of MEK1/2 reveals a differential requirement for ERK1/2
      signalling in the regulation of HIF-1 in response to hypoxia and IGF-1.
AB  - The transcription factor hypoxia-inducible factor 1 (HIF-1) plays a pivotal role
      in tumour growth and progression, and HIF-1 is regulated through a number of
      signalling pathways. Here, we investigated the involvement of the mitogen
      activated protein kinase (MAPK) signalling pathway in HIF-1 regulation. We found
      that overexpression of wild-type (WT) extracellular signal regulated protein
      kinase 1 (ERK1) greatly potentiated HIF-1 activation in hypoxia and HIF-1alpha
      induced in response to insulin growth-like factor 1 (IGF-1). Conversely,
      treatment of tumour cells with the MEK1/2 inhibitors PD98059 or U0216, or
      expression of a dominant-negative form of ERK1 blocked HIF-1 activation in
      hypoxia without affecting HIF-1alpha induction, localization or binding of HIF
      1beta. Interestingly however, the highly selective MEK1/2 inhibitor PD184352 did
      not inhibit HIF-1 activity or vascular endothelial growth factor (VEGF) induced
      in response to hypoxia but blocked HIF-1alpha protein and HIF-1 activity induced
      by IGF-1 stimulation without affecting HIF-1alpha mRNA levels. Finally, we found
      that ERK5 phosphorylation status was not significantly affected by hypoxia in the
      presence or absence of PD184352. Taken together, our data suggest that although
      ERK1/2 signalling is important for HIF-1alpha induction and HIF-1 activity in
      response to IGF-1, it is dispensable for the induction of HIF-1alpha and
      activation of HIF-1 in response to hypoxia.

PMID- 17213818
TI  - Deficiency of the Cockayne syndrome B (CSB) gene aggravates the genomic
      instability caused by endogenous oxidative DNA base damage in mice.
AB  - The Cockayne syndrome B protein (CSB) has long been known to be involved in the
      repair of DNA modifications that block the RNA polymerase in transcribed DNA
      sequences (transcription-coupled repair). Recent evidence suggests that it also
      has a more general role in the repair of oxidative DNA base modifications such as
      7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxoG). In mammalian cells, 8-oxoG is a
      substrate of the repair glycosylase OGG1. Mice without this enzyme accumulate 8
      oxoG in the genome and have elevated spontaneous mutation rates. To elucidate the
      role of CSB in the prevention of mutations by oxidative DNA base damage, we have
      generated mice that are deficient in Csb or Ogg1 or both genes and carry a non
      transcribed bacterial lacI gene for mutation analysis (Big Blue mice). Our
      results indicate that the overall spontaneous mutation frequencies in the livers
      of Csb(m/m)/Ogg1-/- -mice are elevated not only compared with heterozygous
      control mice (factor 3.3), but also with Ogg1-/- -animals (factor 1.6). Sequence
      analysis revealed that the additional mutations caused by CSB deficiency in an
      Ogg1-/- background are mostly G:C to T:A transversions and small deletions. For
      all mouse strains, the background levels of oxidative purine modifications in the
      livers correlate linearly with the numbers of G:C to T:A transversions observed.
      The data indicate that CSB is involved in the inhibition of mutations caused by
      spontaneous oxidative DNA base damage in a non-transcribed gene.

PMID- 17213819
TI  - DNA-PK phosphorylation sites on Oct-1 promote cell survival following DNA damage.
AB  - Octamer transcription factor-1 (Oct-1) has recently been shown to function as a
      stress sensor that promotes cell survival subsequent to DNA damage. Here, we show
      that the survival signal imparted by Oct-1 following exposure to ionizing
      radiation (IR) is dependent upon DNA-dependent protein kinase (DNA-PK)-dependent
      phosphorylation of a cluster of 13 specific ser/thr residues within the N
      terminal transcriptional regulatory domain of Oct-1. Although IR treatment did
      not affect the recruitment of Oct-1 to the histone H2B promoter, the recruitment
      of RNA polymerase II, TATA-binding protein and histone H4 acetylation were
      strongly reduced, consistent with a decrease in Oct-1 transcriptional regulatory
      potential following IR exposure. Ser/Thr-Ala substitution of 13 sites present in
      Oct-1 transcriptional regulatory domain eliminated Oct-1 phosphorylation
      subsequent to IR exposure. Further, these substitutions prevented Oct-1 from
      rescuing the survival of IR-treated Oct-1-/- murine embryonic fibroblasts,
      providing a direct link between DNA-PK-dependent phosphorylation and the
      contribution of Oct-1 to cell survival. These results implicate Oct-1 as a
      primary effector in a DNA-PK-dependent cell survival pathway that is activated by
      double-stranded DNA breaks.

PMID- 17213820
TI  - The mouse soluble GFRalpha4 receptor activates RET independently of its ligand
      persephin.
AB  - Glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) all
      signal through the transmembrane receptor tyrosine kinase RET. The signalling
      complex consists of GFLs, GPI-anchored ligand binding GDNF family receptor alphas
      (GFRalphas) and RET. Signalling via RET is required for the development of the
      nervous system and the kidney, as well as for spermatogenesis. However,
      constitutive activation of RET is implicated as a cause in several diseases.
      Mutations of the RET proto-oncogene cause the inherited cancer syndrome multiple
      endocrine neoplasia type 2 (MEN 2). Recently, it has been suggested that
      mutations in the persephin binding GFRalpha4 receptor may have a potentially
      modifying role in MEN 2. Several naturally occurring, different splice variants
      of the mammalian GFRalpha4 have been reported. A 7 bp insertion-mutation in the
      human GFRalpha4 gene causes a shift of reading frame and thereby changes the
      balance between the transcripts encoding GPI-anchored and soluble GFRalpha4
      receptors. We report here that the mammalian soluble GFRalpha4 can activate RET
      independently of its preferential ligand, persephin. Our data show that soluble
      GFRalpha4 can associate with, and induce, phosphorylation of RET. In addition,
      our data show that this isoform of GFRalpha4 can induce downstream signalling, as
      well as neuronal survival and differentiation, in the absence of persephin. These
      results suggest that, in line with the previous report, GFRalpha4 may be a
      candidate gene for, or modifier of, the MEN 2 diseases.

PMID- 17213821
TI  - COX-2 involvement in breast cancer metastasis to bone.
AB  - Cyclooxygenase-2 (COX-2) is expressed in 40% of human invasive breast cancers.
      Bone is the predominant site of metastasis in case of breast cancer. We
      investigated the role of COX-2 in a suitable mouse model of breast cancer
      metastasis to bone using the whole-body luciferase imaging of cancer cells. We
      provide several lines of evidence that COX-2 produced in breast cancer cells is
      important for bone metastasis in this model including (1) COX-2 transfection
      enhanced the bone metastasis of MDA-435S cells and (2) breast cancer cells
      isolated and cultured from the bone metastases produced significantly more
      prostaglandin E(2) (an important mediator of COX-2) than the parental injected
      cell populations of breast cancer cells. Next, we found that a COX-2 inhibitor,
      MF-tricyclic, inhibited bone metastasis caused by a bone-seeking clone both in
      prevention regimen (in which case mice started receiving MF-tricyclic 1 week
      before the injection of cancer cells) and in treatment regimen (in which case
      mice received MF-tricyclic after the development of bone metastasis). These
      studies indicate that COX-2 produced in breast cancer cells may be vital to the
      development of osteolytic bone metastases in patients with breast cancer, and
      that COX-2 inhibitors may be useful in halting this process.

PMID- 17213822
TI  - Cooperative interaction between ETS1 and GFI1 transcription factors in the
      repression of Bax gene expression.
AB  - The proto-oncoproteins ETS1 and growth factor independent-1 (GFI1) are implicated
      in cell growth and differentiation in various types of cells, and their
      deregulated expression is involved in malignant transformation. Here, we report
      that ETS1 and GFI1 interact and affect gene expression through their cross-talk.
      Co-immunoprecipitation analyses and glutathione-S-transferase pull-down assays
      revealed that ETS1 bound directly to GFI1 via its Ets domain, and GFI1 bound to
      ETS1 via its zinc-finger domain. Luciferase (Luc) assays using artificial
      reporters showed that GFI1 repressed ETS1-mediated transcriptional activation and
      ETS1 repressed GFI1-mediated transcriptional activation, in a dose-dependent
      manner. However, in the Bax promoter where the Ets- and Gfi-binding sites (EBS
      and GBS) are adjacent, ETS1 and GFI1 cooperatively reduced activation. Site
      directed mutagenesis on the EBS and GBS of the Bax promoter showed that both
      binding sites were necessary for full repression. Chromatin immunoprecipitation
      analyses confirmed that an ETS1-GFI1 complex formed on the Bax promoter even when
      either EBS or GBS was mutated. Introduction of small interfering RNA against ETS1
      and/or GFI1 enhanced endogenous Bax gene expression. Our results suggest that the
      interaction between ETS1 and GFI1 facilitates their binding to specific sites on
      the Bax promoter and represses Bax expression in vivo.

PMID- 17213823
TI  - Cancer risks among BRCA1 and BRCA2 mutation carriers.
AB  - BRCA1 and BRCA2 mutations increase breast and ovarian cancer risks substantially
      enough to warrant risk reduction surgery, despite variable risk estimates.
      Underlying this variability are methodological issues, and also complex genetic
      and nongenetic effects. Although many modifying factors are unidentified, known
      factors can already be incorporated in individualised risk prediction.

PMID- 17213824
TI  - Concurrent irinotecan, oxaliplatin and UFT in first-line treatment of metastatic
      colorectal cancer: a phase I study.
AB  - The feasibility of combining UFT plus leucovorin (LV) with alternating irinotecan
      and oxaliplatin was investigated in the first-line treatment of patients with
      advanced colorectal cancer. Twenty-five patients, median age 63 (range 24-79)
      years, World Health Organisation performance status 0-2 and median four marker
      lesions, received irinotecan 180 mg m(-2) on day 1, oxaliplatin 85-100 mg m(-2)
      on day 15 and UFT 200-300 mg m(-2) day(-1) with LV 90 mg day(-1), days 1-21 of a
      28-day cycle. Patients were treated in cohorts of three. At the highest dose
      (irinotecan 180 mg m(-2), oxaliplatin 100 mg m(-2) and UFT 300 mg m(-2) day(-1)),
      three of four patients experienced grade 3 toxicity. Diarrhoea, lethargy and
      vomiting were dose-limiting. Three of nine patients had grade 2 toxicities at the
      maximum tolerated dose (irinotecan 180 mg m(-2), oxaliplatin 100 mg m(-2) and UFT
      250 mg m(-2) day(-1)). There were no grade 3 toxicities in the first month of
      therapy. The overall response rate was 71% in 21 evaluable patients; progression
      free survival was 8.8 months. Alternating irinotecan and oxaliplatin plus UFT is
      an effective and well-tolerated first-line treatment for patients with advanced
      colorectal cancer. We recommend a dose of irinotecan 180 mg m(-2) on day 1,
      oxaliplatin 100 mg m(-2) on day 15 and UFT 250 mg m(-2) day(-1) with LV 90 mg
      day(-1) on days 1-21 of a 28-day cycle for future studies.

PMID- 17213825
TI  - Specificity of serum prostate-specific antigen determination in the Finnish
      prostate cancer screening trial.
AB  - Specificity constitutes a component of validity for a screening test. The number
      of false-positive (FP) results has been regarded as one of major shortcomings in
      prostate cancer screening. We estimated the specificity of serum prostate
      specific antigen (PSA) determination in prostate cancer screening using data from
      a randomised, controlled screening trial conducted in Finland with 32 000 men in
      the screening arm. We calculated the specificity as the proportion of men with
      negative findings (screen negatives, SN) relative to those with negative and FP
      results (SN/(SN+FP)). A SN finding was defined as either PSA</=4 ng ml(-1) or PSA
      3.0-3.9 ng ml(-1) combined with a negative ancillary test (digital rectal
      examination, DRE or free/total, F/T PSA ratio). False positives were those with
      positive screening test followed by a negative diagnostic examination. Of the 30
      194 eligible men, 20 794 (69%) attended the first screening round and 1968 (9.5%)
      had a screen-positive finding. A total of 508 prostate cancers were detected at
      screening (2.4%). Hence, the number of SN findings was 18 825 and the number of
      FP results 1358. Specificity was estimated as 0.933 (18 825 out of 20 183) with
      95% confidence interval (CI) 0.929-0.936. Specificity decreased with age. Digital
      rectal examination as ancillary examination had similar or higher specificity
      than F/T PSA. In the second screening round, specificity was slightly lower
      (0.912, 95% CI 0.908-0.916). The specificity of PSA screening in the Finnish
      screening trial is acceptable. Further improvement in specificity could, however,
      improve acceptability of screening and decrease screening costs.

PMID- 17213826
TI  - Hypoxia-regulated carbonic anhydrase IX expression is associated with poor
      survival in patients with invasive breast cancer.
AB  - Tumour hypoxia is a microenvironmental factor related to poor response to
      radiation, chemotherapy, genetic instability, selection for resistance to
      apoptosis, and increased risk of invasion and metastasis. Hypoxia-regulated
      carbonic anhydrase IX (CA IX) has been studied in various tumour sites and its
      expression has been correlated with the clinical outcome. The purpose of this
      study was to investigate the correlation of CA IX expression with outcome in
      patients with invasive breast cancer. We conducted a retrospective study
      examining the effects of carbonic anhydrase IX (CA IX) on survival in patients
      with breast cancer. To facilitate the screening of multiple tissue blocks from
      each patient, tissue microarrays were prepared containing between two and five
      representative samples of tumour per patient. Immunohistochemistry was used to
      examine expression of CA IX in patients with breast cancer. The study includes a
      cohort of 144 unselected patients with early invasive breast cancer who underwent
      surgery, and had CA IX expression and follow-up data available for analysis. At
      the time of analysis, there were 28 deaths and median follow-up of 48 months with
      96% of patients having at least 2 years of follow-up. CA IX was negative for 107
      patients (17 deaths) and positive for 37 patients (11 deaths). Kaplan-Meier
      survival curves show that survival was superior in the CA IX-negative group with
      a 2-year survival of 97% for negatives and 83% for positives (log-rank test
      P=0.01). Allowing for potential prognostic variables in a Cox regression
      analysis, CA IX remained a significant independent predictor of survival
      (P=0.035). This study showed in both univariate and multivariate analysis that
      survival is significantly inferior in patients with tumour expressing CA IX.
      Prospective studies are underway to investigate this correlation in clinical
      trial setting.

PMID- 17213828
TI  - Evidence for PDGFRA, PDGFRB and KIT deregulation in an NSCLC patient.

PMID- 17213827
TI  - DNA repair capacity as a possible biomarker of breast cancer risk in female BRCA1
      mutation carriers.
AB  - The BRCA1 gene product helps to maintain genomic integrity through its
      participation in the cellular response to DNA damage: specifically, the repair of
      double-stranded DNA breaks. An impaired cellular response to DNA damage is a
      plausible mechanism whereby BRCA1 mutation carriers are at increased risk of
      breast cancer. Hence, an individual's capacity to repair DNA may serve as a
      useful biomarker of breast cancer risk. The overall aim of the current study was
      to identify a biomarker of DNA repair capacity that could distinguish between
      BRCA1 mutation carriers and non-carriers. DNA repair capacity was assessed using
      three validated assays: the single-cell alkaline gel electrophoresis (comet)
      assay, the micronucleus test, and the enumeration of gamma-H2AX nuclear foci. DNA
      repair capacity of peripheral blood lymphocytes from 25 cancer-free female
      heterozygous BRCA1 mutation carriers and 25 non-carrier controls was assessed at
      baseline and following cell exposure to gamma-irradiation (2 Gy). We found no
      significant differences in the mean tail moment, in the number of micronuclei or
      in the number of gamma-H2AX nuclear foci between the carriers and non-carriers at
      baseline, and following gamma-irradiation. These data suggest that these assays
      are not likely to be useful in the identification of women at a high risk for
      breast cancer.

PMID- 17213830
TI  - Life and death in the granuloma: immunopathology of tuberculosis.
AB  - During tuberculosis (TB) infection, the granuloma provides the microenvironment
      in which antigen-specific T cells colocate with and activate infected macrophages
      to inhibit the growth of Mycobacterium tuberculosis. Although the granuloma is
      the site for mycobacterial killing, virulent mycobacteria have developed a
      variety of mechanisms to resist this macrophage-mediated killing. These surviving
      mycobacteria become dormant, however, if host cellular immunity or the signals
      maintaining granuloma structure wane, or if mycobacteria resume replication,
      leading to reactivation of TB. This balance of life and death applies not only to
      the mycobacterium but also to the host macrophages that may undergo apoptosis or
      necrosis, leading to the characteristic caseous necrosis within the granuloma,
      and the potential spread of TB infection. The immunological factors controlling
      the development and maintenance of the granuloma will be reviewed.

PMID- 17213831
TI  - A question of self-preservation: immunopathology in influenza virus infection.
AB  - Influenza A viruses that circulate normally in the human population cause a
      debilitating, though generally transient, illness that is sometimes fatal,
      particularly in the elderly. Severe complications arising from pandemic influenza
      or the highly pathogenic avian H5N1 viruses are often associated with rapid,
      massive inflammatory cell infiltration, acute respiratory distress, reactive
      hemophagocytosis and multiple organ involvement. Histological and pathological
      indicators strongly suggest a key role for an excessive host response in
      mediating at least some of this pathology. Here, we review the current literature
      on how various effector arms of the immune system can act deleteriously to
      initiate or exacerbate pathological damage in this viral pneumonia. Generally,
      the same immunological factors mediating tissue damage during the anti-influenza
      immune response are also critical for efficient elimination of virus, thereby
      posing a significant challenge in the design of harmless yet effective
      therapeutic strategies for tackling influenza virus.

PMID- 17213832
TI  - Shigella's ways of manipulating the host intestinal innate and adaptive immune
      system: a tool box for survival?
AB  - Shigella, a Gram-negative invasive enteropathogenic bacterium, causes the
      rupture, invasion and inflammatory destruction of the human colonic epithelium.
      This complex and aggressive process accounts for the symptoms of bacillary
      dysentery. The so-called invasive phenotype of Shigella is linked to expression
      of a type III secretory system (TTSS) injecting effector proteins into the
      epithelial cell membrane and cytoplasm, thereby inducing local but massive
      changes in the cell cytoskeleton that lead to bacterial internalization into non
      phagocytic intestinal epithelial cells. The invasive phenotype also accounts for
      the potent pro-inflammatory capacity of the microorganism. Recent evidence
      indicates that a large part of the mucosal inflammation is initiated by
      intracellular sensing of bacterial peptidoglycan by cytosolic leucine-rich
      receptors of the NOD family, particularly NOD1, in epithelial cells. This causes
      activation of the nuclear factor kappa B and c-JunNH(2)-terminal-kinase pathways,
      with interleukin-8 appearing as a major chemokine mediating the inflammatory
      burst that is dominated by massive infiltration of the mucosa by
      polymorphonuclear leukocytes. Not unexpectedly, this inflammatory response, which
      is likely to be very harmful for the invading microbe, is regulated by the
      bacterium itself. A group of proteins encoded by Shigella, which are injected
      into target cells by the TTSS, has been recently recognized as a family of potent
      regulators of the innate immune response. These enzymes target key cellular
      functions that are essential in triggering the inflammatory response, and more
      generally defense responses of the intestinal mucosa. This review focuses on the
      mechanisms employed by Shigella to manipulate the host innate response in order
      to escape early bacterial killing, thus ensuring establishment of its infectious
      process. The escape strategies, the possible direct effect of Shigella on B and T
      lymphocytes, their impact on the development of adaptive immunity, and how they
      may help explain the limited protection induced by natural infection are
      discussed.

PMID- 17213833
TI  - Acceleration of R5 HIV replication by polymorphonuclear neutrophils in cultures
      of macrophages.
AB  - Cell-to-cell contact between monocyte-derived macrophages (MDM) and endothelial
      cells has resulted in the increased proliferation of CC chemokine receptor 5/M
      tropic (R5) human immunodeficiency virus (HIV) in MDM. In the present study, R5
      HIV replication was shown to be increased by polymorphonuclear neutrophils (PMN)
      in MDM cultures through the soluble factors released from these PMN. The
      replication of R5 HIV in MDM was greatly enhanced when PMN were added to
      cultures. An increase in the replication of R5 HIV was also demonstrated when the
      virus was replicated in MDM cultured in a double chamber transwell with PMN.
      Chemokine ligand (CCL) 2 and interleukin (IL)-10 were detected in culture fluids
      of PMN exposed to R5 HIV. The replication of R5 HIV was not accelerated in
      cultures of MDM and PMN in a double chamber transwell supplemented with a mixture
      of monoclonal antibodies directed against CCL2 and IL-10. Similarly, the
      replication of R5 HIV was accelerated in MDM cultures supplemented with a mixture
      of recombinant CCL2 and IL-10. These results indicated that, in response to the
      viral stimulation, PMN produce CCL2 and IL-10 and enhance the replication of R5
      HIV in MDM cultures.

PMID- 17213834
TI  - Regulation of mouse Heparanase gene expression in T lymphocytes and tumor cells.
AB  - Heparanase (HPSE) is an endoglycosidase that cleaves heparan sulfate (HS) and
      plays an important role in tumor metastasis, angiogenesis and inflammation. The
      regulation of HPSE expression and function is tightly controlled and the
      increasing use of the mouse as an animal model to define the role of HPSE in many
      physiological and pathological settings, makes understanding the regulatory
      mechanisms of HPSE in this species of fundamental importance. However, the
      expression distribution of the mouse Hpse gene and the mechanisms that regulate
      its transcription are poorly defined. In this study, the mouse Hpse gene was
      determined to encode for two mRNA transcripts of 1.9 and 3.2 kb in length with
      identical open reading frames that showed similar tissue expression distribution
      to the human HPSE. The mouse Hpse promoter was cloned and a 478-bp minimal
      promoter was identified that contained regulatory elements responsible for both
      basal promoter activity in mouse tumor cells as well as inducible activity in T
      cells. Mutagenesis and transactivation studies identified a functional site in
      the minimal promoter region for the transcription factor Early growth response
      gene 1 (Egr1). Interestingly, Egr1 acted differentially in mouse tumor cells,
      functioning in an activating or repressive manner in breast carcinoma or melanoma
      cells, respectively. Furthermore, the proximal region of the promoter, identified
      as important in the regulation of Hpse transcription, was shown to become
      accessible in T cells upon cell activation. Significantly, the maximal
      accessibility of the promoter occurred at 16 h post-stimulation, which correlated
      with the induction kinetics of Hpse mRNA expression. In summary, this study
      demonstrates that mouse Hpse is expressed and regulated in a similar manner to
      human HPSE and also provides some novel insights into mechanisms of Hpse gene
      regulation that are likely to be relevant to control of the human gene.

PMID- 17213835
TI  - Specific inhibition of HBV replication in vitro and in vivo with expressed long
      hairpin RNA.
AB  - Activating RNA interference to achieve specific gene silencing has shown promise
      for the development of RNA-based treatment of chronic hepatitis B virus (HBV)
      infection. To further this approach, we assessed the efficacy of expressed long
      hairpin RNAs (lhRNAs) that target the conserved HBx open reading frame of HBV. As
      substrates for Dicer, lhRNAs have the potential to generate multiple short
      interfering RNAs (siRNAs) to enable simultaneous targeting of different sites.
      Two U6 Pol III vectors were constructed that encode anti-HBV lhRNAs with a 62
      base pair stem sequence containing multiple G:U pairings. Assessment in
      transfected cultured cells and also in vivo using the murine hydrodynamic
      injection model showed that one of the lhRNA vectors (lhRNA 1) diminished markers
      of virus replication by 70-90% without evidence of interferon response induction.
      Greatest silencing efficacy was observed for targets that are complementary to
      sequences located at the base of the hairpin stem and this correlated with a
      higher concentration of siRNAs derived from this region of the lhRNA. Although
      lhRNA 1 has the advantage of targeting a greater viral sequence, incomplete
      cellular processing may result in unequal silencing across the span of the viral
      target RNA.

PMID- 17213836
TI  - Pharmacological enhancement of mutated alpha-glucosidase activity in fibroblasts
      from patients with Pompe disease.
AB  - We investigated the use of pharmacological chaperones for the therapy of Pompe
      disease, a metabolic myopathy due to mutations of the gene encoding the lysosomal
      hydrolase alpha-glucosidase (GAA) and characterized by generalized glycogen
      storage in cardiac and skeletal muscle. We studied the effects of two imino
      sugars, deoxynojirimycin (DNJ) and N-butyldeoxynojirimycin (NB-DNJ), on residual
      GAA activity in fibroblasts from eight patients with different forms of Pompe
      disease (two classic infantile, two non-classic infantile onset, four late-onset
      forms), and with different mutations of the GAA gene. We demonstrated a
      significant increase of GAA activity (1.3-7.5-fold) after imino sugar treatment
      in fibroblasts from patients carrying the mutations L552P (three patients) and
      G549R (one patient). GAA enhancement was confirmed in HEK293T cells where the
      same mutations were overexpressed. No increase of GAA activity was observed for
      the other mutations. Western blot analysis showed that imino sugars increase the
      amount of mature GAA molecular forms. Immunofluorescence studies in HEK293T cells
      overexpressing the L552P mutation showed an improved trafficking of the mutant
      enzyme to lysosomes after imino sugar treatment. These results provide a
      rationale for an alternative treatment, other than enzyme replacement, to Pompe
      disease.

PMID- 17213837
TI  - Viral clostridial light chain gene-based control of penicillin-induced
      neocortical seizures.
AB  - Restraining excitatory neurotransmission within a seizure focus provides a
      nondestructive treatment strategy for intractable neocortical epilepsy.
      Clostridial toxin light chain (LC) inhibits synaptic transmission by digesting a
      critical vesicle-docking protein, synaptobrevin, without directly altering
      neuronal health. This study tests the treatment efficacy of adenoviral vector
      delivered LC (AdLC) on a model of seizures in rats induced by motor cortex
      penicillin (PCN) injection. LC expression significantly reduced
      electroencephalogram (EEG) frequency, amplitude, duration, and latency compared
      to control groups injected with either an adenoviral vector bearing green
      fluorescent protein (AdGFP) or phosphate buffered solution (PBS).
      Correspondingly, LC gene expression improved behavioral manifestations including
      seizure severity and latency. There was no statistical difference in motor
      function before and after vector administration between treatment and control
      groups. Histological analysis revealed spatially discrete LC expression with
      corresponding synaptobrevin depletion in the cortex surrounding the injection
      site. Thus, vector-mediated LC gene delivery is capable of improving both the EEG
      and behavioral manifestations of PCN-induced focal neocortical seizures through
      synaptobrevin depletion.

PMID- 17213839
TI  - A seventh locus for otosclerosis, OTSC7, maps to chromosome 6q13-16.1.
AB  - Otosclerosis is a common form of hearing impairment among white adults with a
      prevalence of 0.3-0.4%. It is caused by abnormal bone homeostasis of the otic
      capsule that compromises free motion of the stapes in the oval window.
      Otosclerosis is in most patients a multifactorial disease, caused by both genetic
      and environmental factors. In some cases, the disease is inherited as a monogenic
      autosomal dominant trait, sometimes with reduced penetrance. However, families
      large enough for genetic linkage studies are extremely rare. To date, five loci
      (OTSC1-5) have been reported, but none of the responsible genes have been cloned
      yet. An additional locus, OTSC6, has been reported to the HUGO nomenclature
      committee but the relevant linkage study has not been published. In this study, a
      genome-wide linkage study was performed in a large Greek pedigree segregating
      autosomal dominant otosclerosis. A seventh locus, OTSC7, was localized on
      chromosome 6q13-16.1 with a multipoint LOD score of 7.5 in the 13.47 cM region
      defined by markers D6S1036 (centromeric) and D6S300 (telomeric). Linkage analysis
      of this new locus in 13 smaller Belgian and Dutch families has identified one
      family from The Netherlands in which allele segregation suggests linkage to this
      region. The overlap between the critical regions of these two families is a 1.06
      Mb interval between the genetic markers D6S1036 (centromeric) and D6S406
      (telomeric) on chromosome 6q13.

PMID- 17213838
TI  - FGF10 missense mutations in aplasia of lacrimal and salivary glands (ALSG).
AB  - Aplasia of lacrimal and salivary glands (ALSG) is an autosomal dominant
      congenital anomaly characterized by aplasia, atresia or hypoplasia of the
      lacrimal and salivary systems. Affected individuals present with irritable eyes
      and dryness of the mouth with variable expressivity. Mutations in FGF10 were
      recently described in ALSG and in lacrimo-auriculo-dento-digital (LADD) syndrome
      which are overlapping clinical entities. We present here two families with ALSG
      associated with missense mutations (R80S and G138E, respectively) affecting
      highly conserved residues in FGF10. The clinical features of these patients
      further broaden the knowledge of FGF10-related phenotypes.

PMID- 17213840
TI  - Multiple mutations responsible for frequent genetic diseases in isolated
      populations.
AB  - The relatively frequent existence of an autosomal recessive disease in an
      isolated population suggests a founder effect. However, in many cases the high
      frequency is due to more than one mutation in either one or several genes.
      Several possibilities have been raised to explain these findings: a chance
      phenomenon, migration of families with affected patients or digenic inheritance.
      Although each of these possibilities may be responsible for a few of the cases,
      in most they are very improbable explanations. A selective advantage may explain
      most of the observations even if it is difficult to prove.

PMID- 17213841
TI  - Methylation analysis of the intergenic differentially methylated region of DLK1
      GTL2 in human.
AB  - Imprinting is a non-Mendelian form of inheritance where epigenetic modifications
      control mono-allelic expression depending on the parental origin. Methylation of
      CpG-dinucleotides at differentially methylated regions (DMRs) is one of the best
      studied mechanisms directing expression to one specific parental allele. We
      studied the methylation patterns of the intergenic (IG)-DMR of DLK1 and GTL2. The
      methylation marks of the IG-DMR were analysed in human gametes, preimplantation
      embryos, amniocytes and blood of babies born after intracytoplasmic sperm
      injection (ICSI) and blood from adults using a bisulphite sequencing technique.
      In oocytes, the IG-DMR was mainly unmethylated while in sperm cells a generally
      methylated pattern was detected. This germ-line specific methylation mark was
      maintained in the preimplantation embryos until the second cleavage stage.
      Afterwards in the preimplantation embryos, intermediate methylation patterns (26
      74% methylation) occurred, which may point to relaxation of the imprints.
      Intermediate patterns were also present in amniocytes, blood from ICSI babies and
      adults. We hypothesise that in the early cleavage stage embryo a strict
      differential methylation pattern is needed for the correct imprint establishment
      of surrounding imprinted genes. Once correct imprinting of the involved gene(s)
      is acquired, a more relaxed state of the IG-region is allowed.

PMID- 17213842
TI  - Refined genomic localization and ethnic differences observed for the IBD5
      association with Crohn's disease.
AB  - Although the general association of the inflammatory bowel disease (IBD) 5 region
      on chromosome 5q31 to Crohn's disease (CD) has been replicated repeatedly, the
      identity of the precise causal variant within the region remains unknown. A
      recent report proposed polymorphisms in solute carrier family 22, member 4
      (SLC22A4) organic cation transporter 1(OCTN1) and solute carrier family 22,
      member 5 (SLC22A5) (OCTN2) as responsible for the IBD5 association, but
      definitive, large-sample comparison of those polymorphisms with others known to
      be in strong linkage disequilibrium was not performed. We evaluated 1879 affected
      offspring and parents ascertained by a North American IBD Genetics Consortium for
      six IBD5 tag single nucleotide polymorphisms (SNPs) to evaluate association
      localization and ethnic and subphenotypic specificity. We confirm association to
      the IBD5 region (best SNP IGR2096a_1/rs12521868, P<0.0005) and show this
      association to be exclusive to the non-Jewish (NJ) population (P=0.00005) (risk
      allele undertransmitted in Ashkenazi Jews). Using Phase II HapMap data, we
      demonstrate that there are a set of polymorphisms, spanning genes from prolyl 4
      hydroxylase (P4HA2) through interferon regulatory factor 1 (IRF1) with equivalent
      statistical evidence of association to the reported SLC22A4 variant and that
      each, by itself, could entirely explain the IBD5 association to CD. Additionally,
      the previously reported SLC22A5 SNP is rejected as the potential causal variant.
      No specificity of association was seen with respect to disease type and location,
      and a modest association to ulcerative colitis is also observed. We confirm the
      importance of IBD5 to CD susceptibility, demonstrate that the locus may play a
      role in NJ individuals only, and establish that IRF1, PDLIM, and P4HA2 may be
      equally as likely to contain the IBD5 causal variant as the OCTN genes.

PMID- 17213843
TI  - Towards the plant metabolome and beyond.
AB  - Methods for network-wide analysis are increasingly showing that the textbook view
      of the regulation of plant metabolism is often incomplete and misleading. Recent
      innovations in small-molecule analysis have created the ability to rapidly
      identify and quantify numerous compounds, and these data are creating new
      opportunities for understanding plant metabolism and for plant metabolic
      engineering.

PMID- 17213844
TI  - Acquisition of fear extinction requires activation of NR2B-containing NMDA
      receptors in the lateral amygdala.
AB  - N-methyl-D-aspartate receptors (NMDARs) contribute to synaptic plasticity
      underlying learning in a variety of brain systems. Fear extinction, which
      involves learning to suppress the expression of previously learned fear, appears
      to require NMDAR activation in the amygdala. However, it is unclear whether
      amygdala NMDARs are required for the acquisition of extinction learning, and it
      is unknown whether NR2B-containing NMDARs are required in fear extinction. Here,
      we assessed the effects of selective NR2B blockade with ifenprodil on fear
      extinction learning, and found that both systemic and intra-amygdala ifenprodil
      treatment, given before extinction training, impaired the initial acquisition,
      and subsequent retrieval of fear extinction. These results confirm previous
      evidence showing that NMDARs in the amygdala are involved in fear extinction, and
      additionally show that NR2B-containing NMDARs are required. Contrary to the
      conclusion of previous studies, our findings demonstrate NMDARs are required for
      the initial acquisition, rather than only the retention, of fear extinction
      learning. Thus, our results support a previously not known role for NMDA
      dependent plasticity in the lateral amygdala during the acquisition of fear
      extinction.

PMID- 17213845
TI  - Combination of rimonabant and donepezil prolongs spatial memory duration.
AB  - The observations that the cannabinoid(1)(CB(1)) receptor antagonist/inverse
      agonist, rimonabant, and the selective noncompetitive inhibitor of
      acetylcholinesterase (AChE), donepezil, improve performance in a variety of
      animal memory models, suggest that these neurochemical systems play integral
      roles in cognition. The present study tested whether each of these agents
      administered alone or in combination will prolong the duration of spatial memory.
      Rats were trained in a two-phase radial-arm maze procedure, consisting of
      acquisition and retrieval tests, which were separated by an 18 h delay. Each drug
      was administered 30 min before the acquisition phase, immediately after the
      acquisition phase, or 30 min before the retrieval test to assess
      acquisition/consolidation, consolidation, and retrieval mnemonic processes,
      respectively. Rimonabant or donepezil administered before the acquisition phase,
      but not immediately after acquisition or before retrieval, led to a significant
      decrease in the number of errors committed during the retrieval test. Combined
      administration of subthreshold doses of rimonabant and donepezil that had no
      discernable effects on performance when given alone, enhanced memory. These
      results taken together demonstrate that the delay radial-arm maze task is
      sufficiently sensitive to detect memory enhancing effects of these drugs.
      Moreover, these findings suggest that combined administration of subthreshold
      doses of rimonabant and donepezil can improve memory and may represent a novel
      approach to treat cognitive deficits associated with neurodegenerative disorders.

PMID- 17213846
TI  - Quetiapine prevents anhedonia induced by acute or chronic stress.
AB  - The role of atypical antipsychotics as add-on treatments and as primary mood
      stabilizers in different phases of bipolar disorder is an important current
      research area. Although in bipolar patients the main therapeutic indication of
      quetiapine (QTP) is the management of acute mania, several observations suggest
      that this agent may exert antidepressant as well as antimanic effects. However,
      in our knowledge, there are no preclinical studies supporting this hypothesis.
      Thus, the main goal of the present work was to evaluate the putative
      antidepressant effect of QTP (0.4, 2.0, or 10 mg/kg/day), in comparison to
      amitriptyline (AMI) (2 or 5 mg/kg/day), in rats exposed to acute or chronic
      stress. The administration of QTP, 2 mg/kg/day, prevents the onset of anhedonia
      in rats exposed to a 6-week chronic mild stress (CMS) protocol. The effect of QTP
      has a slow onset, beginning at week 5, and causes a complete recovery from
      anhedonia. In this respect, the effect of QTP is similar to that obtained after
      chronic administration of AMI 2 or 5 mg/kg/day. Our findings also indicate that a
      6-week administration of QTP, 2 or 10 mg/kg/day, has protective effects against
      the onset of anhedonia caused by the exposure to an acute subthreshold stressful
      event in rats that have previously experienced the CMS procedure. The results
      suggest that QTP is able to prevent both the transient mood depression caused by
      acute stress and the long-lasting anhedonic state induced by exposure, over a
      period of weeks, to a variety of unpredictable mild stressors.

PMID- 17213847
TI  - The abused inhalant toluene increases dopamine release in the nucleus accumbens
      by directly stimulating ventral tegmental area neurons.
AB  - Recreational abuse of toluene-containing volatile inhalants by adolescents is a
      significant public health problem. The mechanisms underlying the abuse potential
      of such substances remain unclear, but could involve increased activity in
      mesoaccumbal dopamine (DA) afferents innervating the nucleus accumbens (ACB).
      Here, using in vitro electrophysiology, we show that application of behaviorally
      relevant concentrations of toluene directly stimulates DA neurons in the ventral
      tegmental area (VTA), but not surrounding midbrain regions. Toluene stimulation
      of VTA neurons persists when synaptic transmission is reduced. Moreover, unlike
      non-DA neurons, the magnitude of VTA DA neuron firing does not decline during
      longer exposures designed to emulate 'huffing'. Using dual-probe in vivo
      microdialysis, we show that perfusion of toluene directly into the VTA increases
      DA concentrations in the VTA (somatodendritic release) and its terminal
      projection site, the ACB. These results provide the first demonstration that even
      brief exposure to toluene increases action potential drive onto mesoaccumbal VTA
      DA neurons, thereby enhancing DA release in the ACB. The finding that toluene
      stimulates mesoaccumbal neurotransmission by activating VTA DA neurons directly
      (independently of transynaptic inputs) provide insights into the neural
      substrates that may contribute to the initiation and pathophysiology of toluene
      abuse.

PMID- 17213848
TI  - Haematopoietic stem cell transplantation trends in children over the last three
      decades: a survey by the paediatric diseases working party of the European Group
      for Blood and Marrow Transplantation.
AB  - This paper describes the trends in haematopoietic stem cell transplantation
      (HSCT) activity for children in Europe over the last three decades. We analysed
      31,713 consecutive paediatric HSCTs reported by the European Group for Blood and
      Marrow Transplantation (EBMT) centres between 1970 and 2002. Data were taken from
      the EBMT registry and were compared according to period and centre category
      (paediatric or combined). Since 1996, there has been a significant increase in
      the number of HSCTs performed exclusively by paediatric centres, as well as in
      the number of alternative donor HSCTs, and in the use of peripheral blood stem
      cells (P<0.0001). The number of allogeneic HSCTs (allo-HSCTs) for acute
      lymphoblastic leukaemia, acute myeloblastic leukaemia and chronic myeloid
      leukaemia remained stable, whereas it increased for myelodysplastic syndromes and
      lymphomas, and decreased significantly for non-malignant diseases (P<0.0001).
      Multivariate analysis showed that younger age, human leukocyte antigen
      genoidentical donors, HSCT performed after 1996 and transplant centres performing
      more than 10 allo-HSCT/year were all associated with decreased transplant-related
      mortality (TRM) (P<0.0001). The number of autologus HSCTs (auto-HSCTs) for acute
      leukaemia decreased significantly, whereas it increased for solid tumours
      (P<0.0001). Multivariate analysis showed that both auto-HSCT performed before
      1996 and paediatric solid tumours (P<0.0001) had higher TRM. Indications for
      paediatric HSCT have changed considerably during the last seven years. These
      changes provide tools for decision making in health-care planning and
      counselling.

PMID- 17213849
TI  - Results of the EBMT activity survey 2005 on haematopoietic stem cell
      transplantation: focus on increasing use of unrelated donors.
AB  - This EBMT activity report documents the haematopoietic stem cell transplantation
      (HSCT) activity in Europe in 2005. It provides numbers of HSCT by indication,
      donor type and stem cell source, lists the new practice of planned double
      transplants with allogeneic after autologous HSCT and concentrates on the
      increasing role of unrelated transplants over the last years. In 2005, there were
      24,168 first HSCT, 8890 allogeneic (37%), 15,278 autologous (63%) and 3773
      additional re- or multiple transplants reported from 597 centres in 43
      participating countries. Main indications were leukaemias (7404 (31%; 82%
      allogeneic)); lymphomas (13,825 (57%; 89% autologous)); solid tumours (1655 (7%;
      92% autologous)) and non-malignant disorders (1131 (5%; 93% allogeneic)). A total
      of 671 planned allogeneic after autologous HSCT were reported; the majority for
      myeloma (52%), lymphoma (28%) and acute myeloid leukaemia (11%). Compared to
      2004, there was a 20% increase in allogeneic HSCT; numbers of autologous HSCT
      remained constant. The most noticeable increase was in unrelated HSCT, which
      comprise 41% of all allogeneic HSCT. Unrelated HSCT were preferentially performed
      for leukaemias and in countries with high income according to World Bank
      criteria. These data illustrate the current experience in Europe and form the
      basis for patient counselling and decisions making at health care institutions.

PMID- 17213850
TI  - Chagas disease in a recipient of cord blood transplantation.

PMID- 17213852
TI  - Plagiarism. There are many types of scientific misconduct, but it seems that
      plagiarism is on everybody's mind.

PMID- 17213853
TI  - Chronic lymphocytic leukemia and cryoglobulinemic glomerulonephritis.

PMID- 17213854
TI  - Genes for diabetic nephropathy: sweet prospects on the horizon.
AB  - Familial aggregation of diabetic nephropathy has suggested an important role for
      hereditary factors in the development of this trait. Osterholm et al. provide
      further evidence that a gene on chromosome 3q confers susceptibility to this
      diabetic complication.

PMID- 17213855
TI  - Vitamin D, insulin resistance, and renal disease.
AB  - Chonchol and Scragg report the results of a population study on levels of 25
      hydroxyvitamin D in patients with renal dysfunction. They demonstrate that these
      patients do not show vitamin D deficiency unless renal function is severely
      affected (GFR<29 mL/min/1.73m2), while vitamin D and renal function loss are
      independently associated with insulin resistance. These data provide more solid
      evidence than previous available studies on small patient groups, and pose new
      questions about the mechanisms responsible for progressive renal disease as well
      as potential effects of vitamin D supplementation.

PMID- 17213856
TI  - Insulin resistance and protein catabolism in non-diabetic hemodialysis patients.
AB  - Chronic kidney disease (CKD) is associated with complex metabolic changes
      including insulin resistance. Siew et al. have highlighted an important
      relationship between insulin resistance and skeletal muscle protein turnover. If
      insulin resistance is implicated in sarcopenia of CKD, further research will be
      required to determine whether interventions that improve insulin sensitivity
      improve clinical outcomes and cardiovascular risk in CKD.

PMID- 17213858
TI  - Letter on the relation between serum Ca, PO4, and PTH with mortality in dialysis
      patients.

PMID- 17213860
TI  - Dopamine receptor modulation of hypoxic-ischemic neuronal injury in striatum of
      newborn piglets.
AB  - Dopamine receptors regulate glutamatergic neurotransmission and Na(+),K(+)-ATPase
      via protein kinase A (PKA) and dopamine- and cAMP-regulated phosphoprotein of 32
      kDa (DARPP-32)-dependent signaling. Consequently, dopamine receptor activation
      may modulate neonatal hypoxic-ischemic (H-I) neuronal damage in the selectively
      vulnerable putamen enriched with dopaminergic receptors. Piglets subjected to two
      durations of hypoxia followed by asphyxic cardiac arrest were treated with a D1
      like (SCH23390) or D2-like (sulpiride) receptor antagonist. At 4 days of recovery
      from less severe H-I, the remaining viable neurons in putamen were 60% of
      control, but nearly completely salvaged by pretreatment with SCH23390 or
      sulpiride. After more severe H-I in which only 18% of neurons were viable,
      partial neuroprotection was seen with SCH23390 pretreatment (50%) and
      posttreatment (39%) and with sulpiride pretreatment (35%), but not with sulpiride
      posttreatment (24%). Dopamine was significantly elevated in microdialysis samples
      from putamen during asphyxia and the first 15 mins of reoxygenation. Pretreatment
      with SCH23390 or sulpiride largely attenuated the increased nitrotyrosine and the
      decreased Na(+),K(+)-ATPase activity that occurred at 3 h after severe H-I.
      Pretreatment with SCH23390, but not sulpiride, also attenuated H-I-induced
      increases in PKA-dependent phosphorylation of Thr34 on DARPP-32, Ser943 on the
      alpha subunit of Na(+),K(+)-ATPase, and Ser897 of the N-methyl-D-aspartate (NMDA)
      receptor NR1 subunit. These findings indicate that D1 and D2 dopamine receptor
      activation contribute to neuronal death in newborn putamen after H-I in
      association with increased protein nitration and decreased Na(+),K(+)-ATPase
      activity. Furthermore, mechanisms of D1 receptor toxicity may involve DARPP-32
      dependent phosphorylation of NMDA receptor NR1 and Na(+),K(+)-ATPase.

PMID- 17213861
TI  - Ischemic preconditioning reveals that GLT1/EAAT2 glutamate transporter is a novel
      PPARgamma target gene involved in neuroprotection.
AB  - Excessive levels of extracellular glutamate in the nervous system are excitotoxic
      and lead to neuronal death. Glutamate transport, mainly by glutamate transporter
      GLT1/EAAT2, is the only mechanism for maintaining extracellular glutamate
      concentrations below excitotoxic levels in the central nervous system. We
      recently showed that neuroprotection after experimental ischemic preconditioning
      (IPC) involves, at least partly, the upregulation of the GLT1/EAAT2 glutamate
      transporter in astrocytes, but the mechanisms were unknown. Thus, we decided to
      explore whether activation of the nuclear receptor peroxisome proliferator
      activated receptor (PPAR) gamma, known for its antidiabetic and antiinflammatory
      properties, is involved in glutamate transport. First, we found that the
      PPARgamma antagonist T0070907 inhibits both IPC-induced tolerance and reduction
      of glutamate release after lethal oxygen-glucose deprivation (OGD) (70.1%+/-3.4%
      versus 97.7%+/-5.2% of OGD-induced lactate dehydrogenase (LDH) release and
      61.8%+/-5.9% versus 85.9%+/-7.9% of OGD-induced glutamate release in IPC and
      IPC+T0070907 1 mumol/L, respectively, n=6 to 12, P<0.05), as well as IPC-induced
      astrocytic GLT-1 overexpression. IPC also caused an increase in nuclear PPARgamma
      transcriptional activity in neurons and astrocytes (122.1%+/-8.1% and 158.6%+/
      22.6% of control PPARgamma transcriptional activity, n=6, P<0.05). Second, the
      PPARgamma agonist rosiglitazone increased both GLT-1/EAAT2 mRNA and protein
      expression and [(3)H]glutamate uptake, and reduced OGD-induced cell death and
      glutamate release (76.3%+/-7.9% and 65.5%+/-15.1% of OGD-induced LDH and
      glutamate release in rosiglitazone 1 mumol/l, respectively, n=6 to 12, P<0.05).
      Finally, we have identified six putative PPAR response elements (PPREs) in the
      GLT1/EAAT2 promoter and, consistently, rosiglitazone increased fourfold
      GLT1/EAAT2 promoter activity. All these data show that the GLT1/EAAT2 glutamate
      transporter is a target gene of PPARgamma leading to neuroprotection by
      increasing glutamate uptake.

PMID- 17213863
TI  - Spatial specificity of BOLD versus cerebral blood volume fMRI for mapping
      cortical organization.
AB  - Intravascular contrast agents are used in functional magnetic resonance imaging
      to obtain cerebral blood volume (CBV) maps of cortical activity. Cerebral blood
      volume imaging with MION (monocrystalline-iron-oxide-nanoparticles) increases the
      sensitivity of functional imaging compared with the blood oxygenation level
      dependent (BOLD) signal (Leite et al, 2002; Mandeville et al, 1998; Vanduffel et
      al, 2001). It therefore represents an attractive method for obtaining detailed
      maps of cortical organization (Vanduffel et al, 2001; Zhao et al, 2005). However,
      it remains to be determined how the spatial profile of CBV maps of cortical
      activity derived with MION compares with the profile of BOLD activation maps
      under a variety of different stimulation conditions. We used several stimulation
      paradigms to compare the spatial specificity of CBV versus BOLD activation maps
      in macaque area V1 at 4.7 T. We observed that: (1) CBV modulation is relatively
      stronger in deep cortical layers compared with BOLD, in agreement with studies in
      cats (Harel et al, 2006) and rodents (Lu et al, 2004; Mandeville and Marota,
      1999) and (2) surprisingly, under large surround stimulation conditions, CBV maps
      extend along the cortical surface to cover large (>10 mm) regions of the cortex
      that are devoid of significant BOLD modulation. We conclude that the spatial
      profiles of BOLD and CBV activity maps do not coregister across all stimulus
      conditions, and therefore do not necessarily represent equivalent transforms of
      the neural response. Cerebral blood volume maps should be interpreted with care,
      in the context of the particular experimental paradigm applied.

PMID- 17213862
TI  - Contribution of poly(ADP-ribose) polymerase to postischemic blood-brain barrier
      damage in rats.
AB  - The nuclear enzyme poly(ADP-ribose) polymerase (PARP) is activated by oxidative
      stress and plays a significant role in postischemic brain injury. We assessed the
      contribution of PARP activation to the blood-brain barrier (BBB) disruption and
      edema formation after ischemia-reperfusion. In male Wistar rats, global cerebral
      ischemia was achieved by occluding the carotid arteries and lowering arterial
      blood pressure for 20 mins. The animals were treated with saline or with the PARP
      inhibitor N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N, N-dimethylacetamide.HCl
      (PJ34); (10 mg/kg, i.v.) before ischemia. After 40 mins, 24, and 48 h of
      reperfusion, the permeability of the cortical BBB was determined after Evans Blue
      (EB) and Na-fluorescein (NaF) administration. The water content of the brain was
      also measured. The permeability of the BBB for EB increased after ischemia
      reperfusion compared with the nonischemic animals after 24 and 48 h reperfusion
      but PARP inhibition attenuated this increase at 48 h (nonischemic: 170+/-9,
      saline: 760+/-95, PJ34: 472+/-61 ng/mg tissue). The extravasation of NaF showed
      similar changes and PJ34 post-treatment attenuated the permeability increase even
      at 24 h. PARP inhibition decreased the brain edema seen at 48 h. Because PARP has
      proinflammatory properties, the neutrophil infiltration of the cortex was
      determined, which showed lower values after PJ34 treatment. Furthermore, PJ34
      treatment decreased the loss of the tight junction protein occludin at 24 and 48
      h. The inhibition of PARP activity accompanied by reduced post-ischemic BBB
      disturbance and decreased edema formation suggests a significant role of this
      enzyme in the development of cerebral vascular malfunction

PMID- 17213864
TI  - Phylogeographic structure in an Australian freshwater shrimp largely pre-dates
      the geological origins of its landscape.
AB  - The phylogeographic structure of cryptic lineages within the freshwater shrimp
      Caridina indistincta Calman, 1926 (Decapoda: Atyidae) was investigated in an
      attempt to unravel any potential genetic influences of Quaternary sea-level
      oscillations. The study was based on mitochondrial DNA sequences from specimens
      from lakes and creeks in the sand dune areas of southeast Queensland, eastern
      Australia. Four divergent lineages were identified, two of which were from
      Moreton and North (N.) Stradbroke Islands. Lineage 'C1' has been found only on
      Moreton Island and the western part of N. Stradbroke Island, whereas 'C2' was
      found on the eastern side of N. Stradbroke Island and a few locations on the
      mainland. These diverged from each other during the Late Miocene/Pliocene and so
      are older than the current landscape in which they are found. Small-scale
      phylogeographic analysis of C1 identified four separate geographic areas, within
      the two islands, whose divergences date to the Pleistocene (approximately 100-300
      thousand years ago ('kya')). The N. Stradbroke Island population of C2 also
      diverged from the mainland during the Pleistocene, as did a sympatric freshwater
      fish Rhadinocentrus ornatus Regan, 1914 (Melanotaeniidae). This implies that the
      ice-age sea-level changes may have structured these populations, although there
      is little observable influence of the last glacial maximum (approximately 18
      kya). Most estimates for the age of the landscape (dunes, lakes) also fall within
      the Pleistocene and so the effect of sea-level change may be seen both in biology
      and geology.

PMID- 17213865
TI  - Reduced genetic structure of north Ethiopian cattle revealed by Y-chromosome
      analysis.
AB  - Ethiopia is considered to be a putative migratory corridor for both Near-East Bos
      taurine and Arabian and Indian B. indicus cattle into East Africa. African
      pastoralism, which is associated with adaptation to specific habitats and farming
      systems, has contributed to the composite constitution of Ethiopian cattle. We
      analyse, for the first time, five Y-chromosome microsatellite markers from seven
      north Ethiopian cattle populations, using a European Holstein-Friesian population
      as a reference, to assess the paternal gene pool and to explore the mechanisms
      behind the genetic structure. Our results reveal that the indicine alleles
      predominate in the present populations, with only one animal in the Arado
      carrying the taurine alleles. The north Ethiopian cattle populations with one
      exception (Abergelle) are characterized by a general low Y-chromosome haplotype
      diversity, as well as by a reduced interpopulation variance (Phi(ST)=4.0%), which
      can be a result of strong male-mediated selective sweeps. Population structure
      revealed by multidimensional-scaling analysis differentiates two populations
      (Arado and Abergelle) from the rest. Analysis of molecular variance does not lend
      support to the traditional classification for the populations, which is mainly
      based on physical characteristics. A network analysis indicates two closely
      related founding haplotypes accounting for a large proportion (50.0% in Abergelle
      and 85.0-94.7% in others) of north Ethiopian cattle Y-chromosomes. Our findings
      point to a common, but limited, paternal origin of the north Ethiopian cattle
      populations and strong male-mediated gene flow among them. The findings also
      provide insight into the historical immigration of cattle into East Africa.

PMID- 17213866
TI  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin affects fluctuating asymmetry of molar shape
      in mice, and an epistatic interaction of two genes for molar size.
AB  - Fluctuating asymmetry (FA), random variation between left and right sides in a
      bilaterally symmetrical character, is a commonly used measure of developmental
      instability that is expected to increase with increasing environmental stress.
      One potential stressor is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a powerful
      toxicant known to disturb tooth development. In this study, mice in the F(2)
      generation produced from an intercross between two inbred strains (C57BL/6J and
      AKR/J) were exposed in utero to TCDD. We hypothesized that TCDD would increase FA
      in the molars of exposed mice over that of the control mice. In addition, we
      hypothesized that we would discover genes for molar size, shape or asymmetry
      whose expression would be affected by TCDD. We detected a very small, but
      significant, increase in FA of molar shape (but not size) in the TCDD-exposed
      mice compared to the control mice, although molar size and shape did not differ
      between these groups. Although we did not uncover any genes that acted
      differently in the TCDD exposed and control groups, we did identify two genes
      whose dominance by additive epistatic effect on molar size was affected by TCDD.
      We concluded that although TCDD may be affecting the expression of some genes
      governing the development of molars in our population of mice, FA of molar size
      and shape is not a particularly sensitive indicator of this effect.

PMID- 17213867
TI  - RNAi and epigenetics: Pol IV is a matchmaker of small RNAs meeting with
      chromatin.

PMID- 17213868
TI  - Sporadic sexual reproduction: sex to some degree.

PMID- 17213869
TI  - Quality of food eaten in English primary schools: school dinners vs packed
      lunches.
AB  - OBJECTIVE: To compare the food and nutrient intakes of primary school children
      eating school dinners and packed lunches. SUBJECTS: Six-hundred and twenty-one 7
      year-old children participating in the Avon Longitudinal Study of Parents and
      Children in South West England. METHODS: Diet was assessed by 3-day unweighed
      food record. RESULTS: The composition of both types of school meals compared
      unfavourably with dietary guidelines. Intakes of energy, non-starch
      polysaccharides (NSP), calcium, iron, folate, retinol equivalents, zinc, copper,
      magnesium, iodine and riboflavin were too low, and intakes of total and saturated
      fat were too high. However, children who ate school dinners had higher lunchtime
      intakes of protein, starch, NSP and most vitamins and minerals and lower intakes
      of sugar (14.2 and 20.9% of energy in school dinners and packed lunches,
      respectively, P<0.001) and saturated fat (12.0 and 16.2%, P<0.001). Only around
      half of the recommended amount of fruit and vegetables was eaten by children
      having either type of school meal. There were also differences in the whole day's
      nutrient intake according to school meal type. Children eating packed lunches had
      lower daily intakes of potassium and zinc, and higher intakes of sugar and
      saturated fat. Differences in nutrient intake were independent of maternal
      education. CONCLUSIONS: The food and nutrient content of both school dinners and
      packed lunches needed improvement. However, the standard of food brought from
      home by children was, if anything, worse than that served at school. Recent moves
      to improve school dinners will need to be complemented by education about what
      constitutes a healthy packed lunch.

PMID- 17213870
TI  - Pharmacogenomics and nutrigenomics: synergies and differences.
AB  - The success of the Human Genome Project and the spectacular development of broad
      genomics tools have catalyzed a new era in both medicine and nutrition. The terms
      pharmacogenomics and nutrigenomics are relatively new. Both have grown out of
      their genetic forbears as large-scale genomics technologies have been developed
      in the last decade. The aim of both disciplines is to individualize or
      personalize medicine and food and nutrition, and ultimately health, by tailoring
      the drug or the food to the individual genotype. This review article provides an
      overview of synergies and differences between these two potentially powerful
      science areas. Individual genetic variation is the common factor on which both
      pharmacogenomics and nutrigenomics are based. Each human is genetically
      (including epigenetics) unique and phenotypically distinct. One of the
      expectations of both technologies is that a wide range of gene variants and
      related single-nucleotide polymorphism will be identified as to their importance
      in health status, validated and incorporated into genotype based strategies for
      the optimization of health and the prevention of disease. Pharmacogenomics
      requires rigorous genomic testing that will be regulated and analyzed by
      professionals and acted on by medical practitioners. As further information is
      obtained on the importance of the interaction of food and the human genotype in
      disease prevention and health, pharmacogenomics can provide an opportunity driver
      for nutrigenomics. As we move from disease treatment to disease prevention, the
      two disciplines will become more closely aligned.

PMID- 17213871
TI  - Health and nutrition education program in primary schools of Crete: changes in
      blood pressure over 10 years.
AB  - OBJECTIVE: To examine the long-term effects of the 'Cretan Health and Nutrition
      Education Program' on blood pressure. SUBJECTS: A representative population of
      176 pupils (85 from the intervention schools and 91 from the control schools).
      DESIGN: Blood pressure, dietary, anthropometrical and physical activity data were
      obtained at baseline (academic year 1992-1993) and at follow-up examination
      (academic year 2001-2002). RESULTS: The findings of the current study revealed
      that the increase over the 10-year period in systolic (SBP) and diastolic blood
      pressure (DBP) was higher in the control group (CG) than in the intervention
      group (IG) (P=0.003 and P<0.001 respectively). Regarding dietary indices, the IG
      were found to have a significantly higher intake of potassium (P=0.018) and
      magnesium (P=0.011) compared to the CG. Furthermore, the decrease in body mass
      index (BMI) z-score observed in the IG was found to differentiate significantly
      from the increase observed in the CG (P=0.042). On the contrary, the increase in
      leisure time, moderate to vigorous physical activities (MVPA) observed in the IG,
      was found to differentiate significantly from the decrease observed in the CG
      (P=0.032). Intervention's effect on SBP was mediated by changes in MVPA (beta=
      0.20, P=0.030) and BMI (beta=0.19, P=0.048). Similarly, intervention's effect on
      DBP was mediated by changes in MVPA (beta=-0.18, P=0.048), BMI (beta=0.26,
      P=0.007) and magnesium intake (beta=-0.20, P=0.048). CONCLUSION: The findings of
      the current study are encouraging, indicating favorable changes in blood
      pressure, micronutrients intake, BMI and physical activity over the 10 years of
      follow-up and 4 years after program's cessation, thus providing some support for
      the effectiveness of school-based health education programs in successfully
      tackling certain chronic disease risk factors early in life.

PMID- 17213872
TI  - Evaluation of body mass index percentiles for assessment of malnutrition in
      children with cystic fibrosis.
AB  - OBJECTIVE: To compare the performance of recently released body mass index
      percentiles (BMIp) with standard anthropometric indexes, including height-for-age
      percentile (HAP), weight-for-age percentile (WAP) and percent ideal body weight
      (%IBW), as measures for nutritional failure in children with cystic fibrosis
      (CF). DESIGN: Cross-sectional analysis of growth and lung function data from 4577
      children with CF reported to the German CF quality assurance (CFQA) project from
      1995 to 2004. RESULTS: Frequency distribution of HAP (mean+/-s.d.: male 30.0+/
      27.5; female 31.3+/-27.4) and WAP (male 28.9+/-27.0; female 29.6+/-26.7) were
      skewed, with significant numbers of patients below the fifth percentiles of a
      healthy reference population. However, because deficits occurred in both measures
      simultaneously, mean %IBW (male 97.0+/-12.1; female 98.1+/-12.3) assumed subjects
      weight close to the nominal weight-for-height at all ages. In contrast, mean BMIp
      was markedly reduced (male 35.7+/-27.9; female 35.6+/-27.2) and steadily declined
      with age. Ideal weight-for-age was significantly lower when predicted by %IBW
      compared with BMIp method, particularly in subjects with shorter-than-average
      stature. Consequently, less CF children were identified with nutritional failure
      according to %IBW method (male 20.5%; female 22.7%) compared with BMIp method
      (male 30.4%; female 28.7%). The clinical relevance of these findings was
      confirmed by stronger correlation of BMIp with impaired %forced expiratory
      volume/s, a marker for disease progression in CF. CONCLUSION: BMIp predicts
      nutritional failure more sensitively and accurately than conventional
      anthropometric indexes, at least in children with CF. Screening of CF patients by
      BMIp could provide an early warning sign and allow for timely therapeutic
      intervention.

PMID- 17213873
TI  - Association of intradialytic blood pressure changes with hospitalization and
      mortality rates in prevalent ESRD patients.
AB  - The relationship between blood pressure (BP) and clinical outcomes among
      hemodialysis patients is complex and incompletely understood. This study sought
      to assess the relationship between blood pressure changes with hemodialysis and
      clinical outcomes during a 6-month period. This study is a secondary analysis of
      the Crit-Line Intradialytic Monitoring Benefit Study, a randomized trial of 443
      hemodialysis subjects, designed to determine whether blood volume monitoring
      reduced hospitalization. Logistic regression was used to estimate the association
      between BP changes with hemodialysis (Deltasystolic blood pressure=postdialysis
      predialysis systoic BP (SBP) and the primary outcome of non-access-related
      hospitalization and death. Subjects whose systolic blood pressure fell with
      dialysis were younger, took fewer blood pressure medications, had higher serum
      creatinine, and higher dry weights. After controlling for baseline
      characteristics, lab variables, and treatment group, subjects whose SBP remained
      unchanged with hemodialysis (N=150, DeltaSBP -10 to 10 mm Hg) or whose SBP rose
      with hemodialysis (N=58, DeltaSBP > or =10 mm Hg) had a higher odds of
      hospitalization or death compared to subjects whose SBP fell with hemodialysis
      (N=230, DeltaSBP < or =-10 mm Hg) (odds ratio: 1.85, confidence interval: 1.15
      2.98; and odds ratio: 2.17, confidence interval: 1.13-4.15). Subjects whose
      systolic blood pressure fell with hemodialysis had a significantly decreased risk
      of hospitalization or death at 6 months, suggesting that hemodynamic responses to
      dialysis are associated with short-term outcomes among a group of prevalent
      hemodialysis subjects. Further research should attempt to elucidate the
      mechanisms behind these findings.

PMID- 17213874
TI  - Effect of combining ACE inhibition with aldosterone blockade on proteinuria and
      renal damage in experimental nephrosis.
AB  - Aldosterone has pro-fibrotic properties and is a potential target for additional
      intervention in patients with chronic renal disease showing resistance to therapy
      during treatment with angiotensin-converting enzyme inhibitors (ACEi). Combining
      ACEi and aldosterone receptor blockade (aldoRB) in proteinuric renal disease
      reduces proteinuria, but effects on proteinuria-induced renal damage are unknown.
      We studied the effect of ACEi/aldoRB in adriamycin nephrosis (AN). Six weeks
      after injection of adriamycin in Wistar rats, randomized treatment with vehicle
      (VEH, n=8), aldoRB (n=12), ACEi (n=10), or a combination of ACEi/aldoRB (n=14)
      was given for 12 weeks. Healthy rats served as controls (n=6). Renal damage was
      quantified by markers of tubular injury (osteopontin (OPN) and kidney injury
      molecule-1 (Kim-1)), pre-fibrotic lesions (alpha-smooth muscle actin (SMA)),
      interstitial fibrosis (IF), and focal glomerulosclerosis (FGS). In AN animals,
      proteinuria was increased compared with controls. ACEi and ACEi/aldoRB
      significantly reduced proteinuria compared with VEH, whereas aldoRB monotherapy
      was without effect. Blood pressure was reduced in ACEi and ACEi/aldoRB compared
      with VEH and aldoRB. OPN and Kim-1 were increased in AN animals, but
      significantly reduced by ACEi/aldoRB. Treatment with ACEi and ACEi/aldoRB
      prevented an increase of SMA, IF, and FGS. In conclusion, ACEi/aldoRB effectively
      reduced proteinuria and markers of tubular injury and prevented renal damage in
      this rat model of chronic proteinuria-induced renal damage.

PMID- 17213876
TI  - TNFA2 and d2 alleles of the tumor necrosis factor alpha gene polymorphism are
      associated with onset/occurrence of idiopathic membranous nephropathy.
AB  - Idiopathic membranous nephropathy (IMN) has a strong association with the major
      histocompatibility complex HLA B8DR3(17)DQ2 haplotype. The tumor necrosis factor
      (TNF)A gene is located within the major histocompatibility complex region on
      chromosome 6. We have studied the influence of two functional polymorphisms; the 
      308 (promoter region) and the TNFd microsatellites on initiation and/or
      progression of IMN. This was a case-control study comparing data from 100
      Caucasians patients (67 male subjects; 67%) with IMN to 232 Caucasians local
      controls (171 male subjects; 74%). We have analyzed genotypes and alleles
      distributions and the role of these polymorphisms in disease progression towards
      end-stage renal failure or patient death. For -308 TNFA polymorphism,
      distribution of genotypes was significantly different between IMN and controls
      (chi(2)=16.25; P=0.0003): the A2 allele frequency was 28.0% in IMN vs 15.3% in
      controls (chi(2)=14.57; P=0.0001). For TNFd polymorphism, alleles distribution
      (from d1 to d7) was also significantly different between IMN and controls
      (chi(2)=56.74; P<0.0001) with both diminished d3 allele frequency (chi(2)=27.30;
      P<0.0001; Pc=0.001) and increased d2 allele frequency (chi(2)=29.95; P<0.0001;
      Pc=0.001) in IMN. We could not isolate any significant and independent influence
      of these different genotypes on IMN disease progression. The TNFA2 and TNFd2
      alleles were strongly associated with occurrence/initiation of IMN and should be
      considered as susceptibility genes for this disease.

PMID- 17213875
TI  - Epoetin use and Kidney Disease Outcomes Quality Initiative hemoglobin targets in
      patients returning to dialysis with failed renal transplants.
AB  - Patients with failed renal transplants represent an increasing proportion of the
      current dialysis population. Although their risk of anemia might be expected to
      be high, whether these patients receive adequate anemia therapy after returning
      to dialysis is unknown. We studied intravenous iron use, epoetin doses, and
      hemoglobin levels in patients with and without failed renal transplants who
      survived for 6 months after initiation of dialysis in the United States between
      1996 and 2001. Of the study population (n=220 557), 9922 (4.5%) had failed renal
      transplants. In spite of a greater likelihood of receiving intravenous iron
      therapy (adjusted odds ratio (AOR) 1.47, P<0.0001) and epoetin (AOR 1.57,
      P<0.0001), patients with failed transplants were more anemic and had higher
      epoetin doses in each month of follow-up. During month 6, patients with failed
      transplants were more likely to have hemoglobin levels below 11 g/dl (AOR 1.50,
      P<0.0001) and to have epoetin-to-hemoglobin ratios above the population median of
      1030 U/week per g/dl (AOR 1.73, P<0.0001). Patients who return to dialysis with
      failed transplants are at a higher risk of anemia than other patients who start
      dialysis; the pattern of lower hemoglobin levels and higher ratios of epoetin-to
      hemoglobin suggests that relative epoetin resistance may be contributory.

PMID- 17213878
TI  - Dietary protein for athletes: from requirements to metabolic advantage.
AB  - The Dietary Reference Intakes (DRI) specify that the requirement for dietary
      protein for all individuals aged 19 y and older is 0.8 g protein.kg-1.d-1. This
      Recommended Dietary Allowance (RDA) is cited as adequate for all persons. This
      amount of protein would be considered by many athletes as the amount to be
      consumed in a single meal, particularly for strength-training athletes. There
      does exist, however, published data to suggest that individuals habitually
      performing resistance and (or) endurance exercise require more protein than their
      sedentary counterparts. The RDA values for protein are clearly set at "...the
      level of protein judged to be adequate... to meet the known nutrient needs for
      practically all healthy people...". The RDA covers protein losses with margins
      for inter-individual variability and protein quality; the notion of consumption
      of excess protein above these levels to cover increased needs owing to physical
      activity is not, however, given any credence. Notwithstanding, diet programs
      (i.e., energy restriction) espousing the virtue of high protein enjoy continued
      popularity. A number of well-controlled studies are now published in which
      "higher" protein diets have been shown to be effective in promoting weight
      reduction, particularly fat loss. The term "higher" refers to a diet that has
      people consuming more than the general populations' average intake of
      approximately 15% of energy from protein, e.g., as much as 30%-35%, which is
      within an Acceptable Macronutrient Distribution Range (AMDR) as laid out in the
      DRIs. Of relevance to athletes and those in clinical practice is the fact that
      higher protein diets have quite consistently been shown to result in greater
      weight loss, greater fat loss, and preservation of lean mass as compared with
      "lower" protein diets. A framework for understanding dietary protein intake
      within the context of weight loss and athletic performance is laid out.

PMID- 17213877
TI  - Reversible movement of switch 1 loop of myosin determines actin interaction.
AB  - The conserved switch 1 loop of P-loop NTPases is implicated as a central element
      that transmits information between the nucleotide-binding pocket and the binding
      site of the partner proteins. Recent structural studies have identified two
      states of switch 1 in G-proteins and myosin, but their role in the transduction
      mechanism has yet to be clarified. Single tryptophan residues were introduced
      into the switch 1 region of myosin II motor domain and studied by rapid reaction
      methods. We found that in the presence of MgADP, two states of switch 1 exist in
      dynamic equilibrium. Actin binding shifts the equilibrium towards one of the
      MgADP states, whereas ATP strongly favors the other. In the light of electron
      cryo-microscopic and X-ray crystallographic results, these findings lead to a
      specific structural model in which the equilibrium constant between the two
      states of switch 1 is coupled to the strength of the actin-myosin interaction.
      This has implications for the enzymatic mechanism of G-proteins and possibly P
      loop NTPases in general.

PMID- 17213879
TI  - Mechanisms of bone remodeling during weight-bearing exercise.
AB  - Exercise-induced mechanical loading can have potent effects on skeletal form and
      health. Both intrinsic and extrinsic factors contribute to bone structure and
      function. Mechanical simuli (e.g., strain magnitude, frequency, rate, and
      gradients, as well as fluid flow and shear stress) have potent influences on bone
      cell cytoskeleton and associated signalling pathways. Although the immature
      skeleton may be more able to benefit from exercise, a skeletally mature
      population can also benefit from exercise programs aimed at increasing the
      functional loads to which the skeleton is exposed. The definitive explanation of
      mechanical-loading and (or) bone-cell mechanotransductive phenomena, however,
      remains elusive. Here, we briefly review the structural and anatomical foundation
      for bone adaptation, focusing on mechanical loading effects on bone, linked to
      the roles of integrins, cytoskeleton, membrane channels, and auto- and paracrine
      factors in bone modeling and remodeling.

PMID- 17213880
TI  - Exercise in the prevention and treatment of maternal-fetal disease: a review of
      the literature.
AB  - Evidence-based guidelines indicate that regular prenatal exercise is an important
      component of a healthy pregnancy. In addition to maintaining physical fitness,
      exercise may be beneficial in preventing or treating maternal-fetal diseases.
      Women who are the most physically active have the lowest prevalence of
      gestational diabetes (GDM), and prevention of GDM may decrease the incidence of
      obesity and type 2 diabetes in both mother and offspring. However, few studies
      have investigated the effectiveness of exercise in delaying or preventing GDM in
      at-risk women, and exercise prescriptions that optimize outcomes for women with
      GDM are lacking. Physically active women are also less likely to develop pre
      eclampsia, and we have proposed the following 4 mechanisms that may explain this
      protective effect: enhanced placental growth and vascularity, reduced oxidative
      stress, reduced inflammation, and correction of disease-related endothelial
      dysfunction. Exercise may also prevent reproductive complications associated with
      maternal obesity. Obesity increases the risk of infertility and miscarriage, and
      weight loss programs that incorporate diet and exercise are a cost-effective
      fertility treatment that may also reduce the probability of obesity-related
      complications during pregnancy. Regular exercise following conception may prevent
      excessive gestational weight gain and reduce post-partum weight retention.

PMID- 17213881
TI  - Mitochondrial oxidative function and type 2 diabetes.
AB  - The cause of insulin resistance and type 2 diabetes is unknown. The major part of
      insulin-mediated glucose disposal takes place in the skeletal muscle, and
      increased amounts of intramyocellular lipid has been associated with insulin
      resistance and linked to decreased activity of mitochondrial oxidative
      phosphorylation. This review will cover the present knowledge and literature on
      the topics of the activity of oxidative enzymes and the electron transport chain
      (ETC) in skeletal muscle of patients with type 2 diabetes. Different methods of
      studying mitochondrial function are described, including biochemical measurements
      of oxidative enzyme and electron transport activity, isolation of mitochondria
      for measurements of respiration, and ATP production and indirect measurements of
      ATP production using nuclear magnetic resonance (NMR) - spectroscopy. Biochemical
      markers of mitochondrial content are also discussed. Several studies show reduced
      activity of oxidative enzymes in skeletal muscle of type 2 diabetics. The
      reductions are independent of muscle fiber type, and are accompanied by visual
      evidence of damaged mitochondria. In most studies, the reduced oxidative enzyme
      activity is explained by decreases in mitochondrial content; thus, evidence of a
      functional impairment in mitochondria in type 2 diabetes is not convincing. These
      impairments in oxidative function and mitochondrial morphology could reflect the
      sedentary lifestyle of the diabetic subjects, and the influence of physical
      activity on oxidative activity and mitochondrial function is discussed. The
      studies on insulin-resistant offspring of type 2 diabetic parents have provided
      important insights in the earliest metabolic defects in type 2 diabetes. These
      defects include reductions in basal ATP production and an attenuated response to
      insulin stimulation. The decreased basal ATP production does not affect overall
      lipid or glucose oxidation, and no studies linking changes in oxidative activity
      and insulin sensitivity in type 2 diabetes have been published. It is concluded
      that evidence of a functional impairment in mitochondria in type 2 diabetes is
      not convincing, and that intervention studies describing the correlation between
      changes in insulin resistance and mitochondrial function in type 2 diabetes are
      lacking. Specific effects of regular physical training and muscular work on
      mitochondrial function and plasticity in type 2 diabetes remain an important area
      of research.

PMID- 17213882
TI  - [Optimal strategies to loose bodyweight for weight-class sports].
AB  - Weight-class sports incite the sportsmen to loose weight to change class and
      increase their chance of success in competition. Although these sports are very
      demanding on the physiological level (high intensity), most of the competitors
      undertake caloric restrictions that are likely to induce physiological disorders
      detrimental to their health and sport performances. Two strategies allow to loose
      bodyweight. The first is maintained over a very short time (less than 1 week),
      the second is maintained over a longer period (several weeks). Managing weight
      reduction, food intake, and physical activities over several weeks is a
      particularly efficient way to conserve the sportsman's performance abilities. On
      the other hand, the transgression of certain principles in only one of these
      fields is enough to deteriorate the sportsman's capacities of performance and
      (or) his health, whatever the duration of the period of the loss of weight.
      During food restriction, the carbohydrate and protein rations must be increased
      to prevent the unavoidable involutions of body composition and performance. In
      spite of food restriction, the training intensity must be high, and only the
      training volume must decrease to remain competitive.

PMID- 17213883
TI  - Work of breathing is increased during exercise with the self-contained breathing
      apparatus regulator.
AB  - The self-contained breathing apparatus (SCBA) increases the expiratory pressure
      required to maintain high rates of ventilation, suggesting that the expiratory
      work of breathing (WOB) is increased; however, this has never been reported. The
      objective of this study, therefore, was to determine if the WOB is increased with
      the SCBA regulator (BA condition) compared with a low-resistance breathing valve
      (RV condition) during exercise. Twelve healthy male subjects underwent two
      randomized exercise trials, consisting of cycling at 150, 180, 210, and 240 W.
      Inspired and expired tidal volumes were measured using a body plethysmograph,
      whereas esophageal pressures were measured with an esophageal balloon. Modified
      Campbell diagrams were created to calculate the resistive and elastic components
      of WOB during inspiration and expiration. There were no differences in WOB
      between BA and RV conditions at 150 W. End-inspiratory and -expiratory lung
      volumes were elevated (p < 0.05) in the BA condition at higher ventilation rates,
      which increased inspiratory elastic work and decreased expiratory elastic work at
      180 and 210 W (p < 0.05). At 240 W (VE=112 +/- 17 L.min-1 in the BA condition),
      active expiratory resistive work increased by 59% +/- 51%, inspiratory elastic
      work increased by 26% +/- 24%, and total WOB increased by 13% +/- 12% in the BA
      condition (p < 0.05). The SCBA regulator causes an increase in the active
      expiratory resistive work to maintain high ventilatory rates and an increase
      inspiratory elastic work through an elevation in lung volumes.

PMID- 17213884
TI  - Sprint training reduces urinary purine loss following intense exercise in humans.
AB  - The influence of sprint training on endogenous urinary purine loss was examined
      in 7 active male subjects (age, 23.1 +/- 1.8 y; body mass, 76.1 +/- 3.1 kg; VO2
      peak, 56.3 +/- 4.0 mL.kg-1.min-1). Each subject performed a 30 s sprint
      performance test (PT), before and after 7 d of sprint training. Training
      consisted of 15 sprints, each lasting 10 s, on an air-braked cycle ergometer
      performed twice each day. A rest period of 50 s separated each sprint during
      training. Sprint training resulted in a 20% higher muscle ATP immediately after
      PT, a lower IMP (57% and 89%, immediately after and 10 min after PT,
      respectively), and inosine accumulation (53% and 56%, immediately after and 10
      min after the PT, respectively). Sprint training also attenuated the exercise
      induced increases in plasma inosine, hypoxanthine (Hx), and uric acid during the
      first 120 min of recovery and reduced the total urinary excretion of purines
      (inosine + Hx + uric acid) in the 24 h recovery period following intense
      exercise. These results show that intermittent sprint training reduces the total
      urinary purine excretion after a 30 s sprint bout.

PMID- 17213885
TI  - Effect of different intensities of active recovery on sprint swimming
      performance.
AB  - Active recovery reduces blood lactate concentration faster than passive recovery
      and, when the proper intensity is applied, a positive effect on performance is
      expected. The purpose of the study was to investigate the effect of different
      intensities of active recovery on performance during repeated sprint swimming.
      Nine male well-trained swimmers performed 8 repetitions of 25 m sprints (8 x 25
      m) interspersed with 45 s intervals, followed by a 50 m sprint test 6 min later.
      During the 45 s and 6 min interval periods, swimmers either rested passively
      (PAS) or swam at an intensity corresponding to 50% (ACT50) and 60% (ACT60) of
      their individual 100 m velocity. Blood lactate was higher during PAS compared
      with ACT50 and ACT60 trials (p < 0.05), whereas plasma ammonia and glycerol
      concentration were not different between trials (p > 0.05). Mean performance time
      for the 8 x 25 m sprints was better in the PAS compared with the ACT50 and ACT60
      trials (PAS: 13.10 +/- 0.07 vs. ACT50: 13.43 +/- 0.10 and ACT60: 13.47 +/- 0.10s,
      p < 0.05). The first 25 m sprint was not different across trials (p > 0.05), but
      performance decreased after sprint 2 during active recovery trials (ACT50 and
      ACT60) compared with the passive recovery (PAS) trial (p < 0.05). Performance
      time for the 50 m sprint performed 6 min after the 8 x 25 m sprints was no
      different between trials (p > 0.05). These results indicate that active recovery
      at intensities corresponding to 50% and 60% of the 100 m velocity during repeated
      swimming sprints decreases performance. Active recovery reduces blood lactate
      concentration, but does not affect performance on a 50 m sprint when 6 min
      recovery is provided. Passive recovery is advised during short-interval repeated
      sprint training in well-trained swimmers.

PMID- 17213886
TI  - Local cold acclimation during exercise and its effect on neuromuscular function
      of the hand.
AB  - Most acclimation research is performed on resting individuals, whereas in real
      life, cold exposure is often accompanied by physical activity. We examined the
      effects of 2 weeks of repeated cold exposure of the hand with or without an
      elevated core temperature from exercise on neuromuscular function of the first
      dorsal interosseus (FDI) muscle and manual performance of the hand. The
      experimental group (4 female, 6 male; age, 25.1 +/- 6.9 y) cooled their hands in
      8 degrees C water for 30 min daily while cycling (50% of heart rate reserve); the
      control group (4 female, 4 male; age, 25.1 +/- 5.7 y) remained still. Manual
      function testing consisted of tactile sensitivity, grip strength, manual
      dexterity, and evoked twitch force in a custom-made myograph. Thermal sensation,
      skin temperature of index finger (Tif) and hand (Tfdi), as well as rectal
      temperature (Tre), were recorded daily. Tre increased significantly during
      bicycling, by 0.6 +/- 0.2 degrees C. Minimal Tif and Tfdi of the groups combined
      increased significantly during exposure days from 8.7 +/- 0.7 degrees C and 12.4
      +/- 2.8 degrees C to 10.1 +/- 1.3 degrees C and 15.0 +/- 3.0 degrees C,
      respectively (p=0.04), with no significant difference between groups. Thermal
      ratings improved significantly on exposure days. Manual function was impaired
      with cooling, but with no significant difference between groups or across time.
      Deterioration of twitch characteristics with cooling did not change with repeated
      cold exposure. Although the increasing core temperature during cold water
      immersion changed the acute temperature response and thermal ratings, it had no
      effect on local cold acclimation or manual function.

PMID- 17213887
TI  - Validity of the 3 min step test in moderate altitude: environmental temperature
      as a confounder.
AB  - The 3 min step test is a widely used method to evaluate physical fitness, but
      whether this method is valid when performed at altitude is unknown. The purpose
      of this study was to examine the effect of altitude on the fitness score of the 3
      min step test, and the role of ambient temperature in this effect. In study I, 11
      healthy volunteers (aged 18.1 +/- 1.1 years) performed a 3 min step test at sea
      level and at altitude (1950 m). Plasma lactate and stress hormones, as indicators
      of metabolic stress, were measured before and after the test. To determine the
      role of ambient temperature, we performed study II at sea level with the same
      step test simulating the altitude temperature condition (24 degrees C at high
      altitude versus 32 degrees C at sea level) with 23 subjects (aged 20.4 +/- 0.4
      y). In study I, plasma lactate of the subjects was elevated during the step test
      at sea level and to a greater extent at high altitude. Plasma cortisol and
      testosterone levels were elevated only at high altitude. However, the heart rate
      (HR) recovery after the step test was faster at high altitude than at sea level,
      producing a better physical fitness index. Furthermore, in study II, we
      demonstrated that the subjects who performed the 3 min step test at 24 degrees C
      exhibited faster HR recovery than at 32 degrees C. The current study therefore
      suggests that environmental conditions leading to temperature variation have
      strong confounding effects on the fitness score of the 3 min step test.

PMID- 17213888
TI  - Non-exhaustive test for aerobic capacity determination in swimming rats.
AB  - The aim of this study was to describe a double-bout exercise test for non
      exhaustive aerobic capacity determination in swimming rats. Adult rats were
      submitted to 4 swimming tests at different intensities (4%, 6%, 7%, and 8% of
      body mass), with intervals of 48 h between them. Two exercise bouts of equal
      intensity lasting 5 min were performed, separated by 2 min with blood collection
      for lactate analysis. For each intensity, delta lactate was determined by
      subtracting lactate concentration at the end of the first effort from the lactate
      at the end of the second effort. Individual linear interpolation of delta lactate
      concentration enabled determination of a "null" delta, equivalent to the critical
      load (CL). Maximal lactate steady state (MLSS) was also determined. The estimated
      CL was of 4.8% body mass and the MLSS was observed at 100% of CL, with blood
      lactate of 5.20 mmol/L. At 90%, blood lactate stabilized, with a progressive
      increase to 110% CL. These results offer a potential determination of aerobic
      capacity in swimming rats.

PMID- 17213889
TI  - Interval training at 95% and 100% of the velocity at VO2 max: effects on aerobic
      physiological indexes and running performance.
AB  - The objective of this study was to analyze the effect of two different high
      intensity interval training (HIT) programs on selected aerobic physiological
      indices and 1500 and 5000 m running performance in well-trained runners. The
      following tests were completed (n=17): (i) incremental treadmill test to
      determine maximal oxygen uptake (VO2 max), running velocity associated with VO2
      max (vVO2 max), and the velocity corresponding to 3.5 mmol/L of blood lactate
      concentration (vOBLA); (ii) submaximal constant-intensity test to determine
      running economy (RE); and (iii) 1500 and 5000 m time trials on a 400 m track.
      Runners were then randomized into 95% vVO2 max or 100% vVO2 max groups, and
      undertook a 4 week training program consisting of 2 HIT sessions (performed at
      95% or 100% vVO2 max, respectively) and 4 submaximal run sessions per week.
      Runners were retested on all parameters at the completion of the training
      program. The VO2 max values were not different after training for both groups.
      There was a significant increase in post-training vVO2 max, RE, and 1500 m
      running performance in the 100% vVO2 max group. The vOBLA and 5000 m running
      performance were significantly higher after the training period for both groups.
      We conclude that vOBLA and 5000 m running performance can be significantly
      improved in well-trained runners using a 4 week training program consisting of 2
      HIT sessions (performed at 95% or 100% vVO2 max) and 4 submaximal run sessions
      per week. However, the improvement in vVO2 max, RE, and 1500 m running
      performance seems to be dependent on the HIT program at 100% vVO2 max.

PMID- 17213890
TI  - Physicochemical analysis of acid-base responses to prolonged moderate exercise in
      late gestation.
AB  - Stewart's physicochemical approach was employed to investigate the safety of an
      average recreational and occupational activity (prolonged moderate exercise) on
      maternal acid-base homeostasis. The responses of 10 healthy, physically active
      pregnant women (PG, gestational age 34-38 weeks) were compared with those of 10
      non-pregnant female controls (CG). Subjects cycled for 40 min at 85% of their
      measured ventilatory threshold (VT). During the transition from rest to exercise,
      hydrogen ion concentration ([H+]) increased significantly and bicarbonate
      concentration ([HCO3-]) decreased significantly in both groups. Total weak acid
      ([Atot]) increased significantly with exercise in both groups, whereas the strong
      ion difference ([SID]) and CO2 tension (PaCO2) did not change significantly with
      exercise. Values for [H+], [HCO3-], PaCO2, [Atot] and [SID] were significantly
      lower in the PG vs. CG under all experimental conditions. Acid-base responses to
      prolonged moderate exercise are quantitatively similar in the pregnant vs. non
      pregnant state. However, pregnant women maintain a lower plasma [H+]
      (approximately 3 neq/L (1 neq/L=1 nmol/L)) throughout rest, exercise, and
      recovery, as a result of lower values for PaCO2 and [Atot], which is partly
      offset by a lower [SID]. The results indicate that prolonged moderate exercise
      appears to be well tolerated by healthy recreationally and occupationally active
      pregnant women.

PMID- 17213891
TI  - Dietary intakes of Canadians in the 1990s using population-weighted data derived
      from the provincial nutrition surveys.
AB  - Provincial nutrition surveys of adults were conducted between 1990 and 1999 in
      Canada. Eight reports have been issued, and one is forthcoming. The purpose of
      this study was to estimate the national dietary intake of adult Canadians, using
      the publicly available data. Group mean-nutrient-intake data from 16 915 adults,
      aged 18 to 84 years, from published provincial reports were collated by age and
      sex for each of 9 provinces (Manitoba data were unavailable). Using Canadian
      census data appropriate to the year of collection, intake data were weighted to
      provide 1 national intake value for each nutrient, by 8 age and sex categories.
      In general, the energy and nutrient intake of adults decreased with age. For
      every age group, with the exception of vitamin C, intake of nutrients by men was
      greater than that by women. On the basis of a comparison of recently recommended
      intakes (Dietary Reference Intakes), the nutrients that are of concern because of
      inadequate intake include dietary fibre, calcium, magnesium, and folate. The data
      demonstrate the impact of folate fortification on folate intake; the mean intake
      became twice that of prefortification levels. This study used group mean-intake
      data; therefore, we cannot make definitive conclusions about the prevalence of
      inadequacy for the nutrients. Because of limitations with some provincial
      response rates, our data should not be construed as representative of the
      Canadian population. However, because these surveys were completed between the
      19701972 Nutrition Canada Survey and the 2004 Canadian Community Health Survey,
      these population-weighted data might be a useful point of comparison for
      monitoring trends in nutrient intake from food.

PMID- 17213897
TI  - A summary of the symposium "Current strategies in the prevention and treatment of
      obesity".
AB  - This symposium addressed important issues related to the prevention and treatment
      of obesity and provided practical advice for health professionals. The importance
      of the maintenance of long-term lifestyle changes were emphasized throughout the
      symposium as being an integral component to the maintenance of healthy body
      masses.

PMID- 17213898
TI  - Skeletal muscle stem cells: a symposium.
AB  - Muscle stem cells are a population of cells that are important for both
      adaptations to exercise and muscle regeneration. This symposium was designed to
      highlight the role of these cells during muscle hypertrophy and development, and
      in response to insulin-like growth factor-1 (IGF-1) induced stimulation.

PMID- 17213899
TI  - Molecular regulation of myogenic progenitor populations.
AB  - Skeletal muscle regeneration and adaptation to exercise require the actions of
      muscle satellite cells. Muscle satellite cells are thought to play an integral
      role in the process of exercise adaptation, but have also been shown to possess
      the capacity to fully regenerate muscle tissue following destructive muscle
      injury. We now know that molecular regulation of satellite cells involves the
      coordinated actions of a series of transcriptional networks that leads to
      myogenic commitment, cell-cycle entry, proliferation, and terminal
      differentiation. Additionally, Pax7 is a paired-box transcription factor that has
      been identified as playing a critical role in satellite cell regulation. It
      remains debatable, however, whether Pax7 is required for the specification of
      satellite cells and (or) whether it is playing a vital role in self-renewal and
      maintenance of the satellite cell population. In recent years, the emergence of
      atypical myogenic progenitor populations has added a new dimension to muscle
      repair, and significant interest has been focused on identifying populations such
      as bone-marrow-derived stem cells that have the ability to contribute to muscle.
      Interestingly, elucidating the molecular regulation of myogenic progenitor
      populations has involved animal models of muscle regeneration, with questionable
      relevance for human muscle adaptation to exercise. This paper highlights the
      current state of knowledge on the molecular regulation of satellite cells,
      explores the potential contribution of atypical myogenic progenitors, and
      discusses the information gathered from animal regeneration models in terms of
      its relevance to the process of exercise adaptation.

PMID- 17213900
TI  - Satellite cell proliferation and skeletal muscle hypertrophy.
AB  - Satellite cells are small, mononuclear cells found in close association with
      striated skeletal muscles cells (myofibers). These cells appear to function as
      reserve myoblasts. A critical role for these cells in the process of muscle
      regeneration following injury has been clearly established. In that role,
      satellite cells have been shown to proliferate extensively. Some of the progeny
      of these cells then fuse with each other to form replacement myofibers, whereas
      others return to quiescence, thereby maintaining this reserve population. In
      response to injury, activated satellite cells can also fuse with damaged but
      viable myofibers to promote repair and regeneration. It has also been observed
      that satellite cells are activated during periods of significantly increased
      muscle loading and that some of these cells fuse with apparently undamaged
      myofibers as part of the hypertrophy process. The observation that the
      inactivation of satellite cell proliferation prevents most of the hypertrophy
      response to chronic increases in loading has lead to the hypothesis that a
      limitation to the expansion of myofiber size is imposed by the number of
      myonuclei present. Recent evidence suggests that a potential limitation to muscle
      hypertrophy, in the absence of a reserve supply of myonuclei, may be the
      inability to sustain increases in ribosomes, thereby limiting translational
      capacity.

PMID- 17213901
TI  - The ABCs of IGF-I isoforms: impact on muscle hypertrophy and implications for
      repair.
AB  - Insulin-like growth factor I (IGF-I) plays a critical role in the growth and
      development of many tissues in the body. It is a key regulator of skeletal muscle
      development, and continues to enhance the ability for muscle to grow and undergo
      repair throughout life. Although the focus of research has been on the molecular
      actions and physiological impact of IGF-I, there has also been a growing
      undercurrent of studies geared toward the characterization of additional
      potentially active peptides produced by the igf1 gene. Alternative splicing of
      the gene results in multiple isoforms that retain the identical sequence for
      mature IGF-I, but also give rise to divergent C-terminal peptides. The peptides
      might modulate the actions, stability, or bioavailability of IGF-I, or they might
      have independent activity. These possibilities have gained the attention of the
      skeletal muscle field, where novel actions of IGF-I could have significant impact
      on muscle mass, strength, and repair.

PMID- 17213902
TI  - Molecular mapping of the shrunken endosperm genes seg8 and sex1 in barley
      (Hordeum vulgare L.).
AB  - A number of mutations affecting seed development in barley (Hordeum vulgare L.)
      have been known for many years; however, to date, no research has been reported
      that elucidates the molecular structure of the causal genes. As a first step, we
      initiated the linkage mapping of the two shrunken endosperm genes seg8 and sex1
      using microsatellite markers. The recessive gene seg8 was mapped in the
      centromeric region of chromosome 7H to a 4.6 cM interval flanked by markers
      GBM1516 and Bmag341. The recessive sex1 gene showed xenia effects and was located
      in the centromeric region of barley chromosome 6H, which is in accordance to the
      previously reported chromosomal location in the classical linkage map. It was
      flanked by markers GBM5012 and GBM1063 in a 4.2 cM interval. EST-derived
      microsatellite markers were used to establish the syntenic relationships to the
      genomic rice sequences. Two orthologous sites on rice chromosome 2 flanking a 4.1
      Mb sequence had homology to the respective barley markers in the sex1 region. For
      the markers in the seg8 region orthologous sites on rice chromosome 6 were
      detected.

PMID- 17213903
TI  - A core linkage map of the bumblebee Bombus terrestris.
AB  - The bumblebee Bombus terrestris is an economically important pollinator and an
      emerging model species in quantitative and population genetics. We generated
      genetic linkage maps for 3 independent mapping populations of B. terrestris. The
      linkage map with the highest resolution had 21 linkage groups, which adequately
      represents the haploid chromosome number of B. terrestris (n = 18). This map can
      be considered saturated, with an average marker distance of 10.3 cM and an
      estimated genome coverage of 81%. Using flow cytometry, we have estimated the
      genome size of this species to be 625 Mb. With an estimated total recombination
      genome length of 2760 cM, this results in a ratio of 226 kb/cM between the
      physical and genetic genome sizes. A recurring set of microsatellites and
      amplified fragment length polymorphism (AFLP) markers allowed the alignment of 14
      linkage groups between the 3 maps. We propose to adopt this core map as a
      reference tool for future genetic and molecular work in B. terrestris.

PMID- 17213904
TI  - Identification and characterization of NBS-LRR class resistance gene analogs in
      faba bean (Vicia faba L.) and chickpea (Cicer arietinum L.).
AB  - A PCR approach with degenerate primers designed from conserved NBS-LRR
      (nucleotide binding site-leucine-rich repeat) regions of known disease-resistance
      (R) genes was used to amplify and clone homologous sequences from 5 faba bean
      (Vicia faba) lines and 2 chickpea (Cicer arietinum) accessions. Sixty-nine
      sequenced clones showed homologies to various R genes deposited in the GenBank
      database. The presence of internal kinase-2 and kinase-3a motifs in all the
      sequences isolated confirm that these clones correspond to NBS-containing genes.
      Using an amino-acid sequence identity of 70% as a threshold value, the clones
      were grouped into 10 classes of resistance-gene analogs (RGA01 to RGA10). The
      number of clones per class varied from 1 to 30. RGA classes 1, 6, 8, and 9 were
      comprised solely of clones isolated from faba bean, whereas classes 2, 3, 4, 5,
      and 7 included only chickpea clones. RGA10, showing a within-class identity of
      99%, was the only class consisting of both faba bean and chickpea clones. A
      phylogenetic tree, based on the deduced amino-acid sequences of 12 representative
      clones from the 10 RGA classes and the NBS domains of 6 known R genes (I2 and Prf
      from tomato, RPP13 from Arabidopsis, Gro1-4 from potato, N from tobacco, L6 from
      flax), clearly indicated the separation between TIR (Toll/interleukin-1 receptor
      homology: Gro1-4, L6, N, RGA05 to RGA10)- and non-TIR (I2, Prf, RPP13, RGA01 to
      RGA04)-type NBS-LRR sequences. The development of suitable polymorphic markers
      based on cloned RGA sequences to be used in genetic mapping will facilitate the
      assessment of their potential linkage relationships with disease-resistance genes
      in faba bean and chickpea. This work is the first to report on faba bean RGAs.

PMID- 17213905
TI  - Mapping of the apple scab-resistance gene Vb.
AB  - Apple scab, caused by the fungus Venturia inaequalis, is the major production
      constraint in temperate zones with humid springs. Normally, its control relies on
      frequent and regular fungicide applications. Because this control strategy has
      come under increasing criticism, major efforts are being directed toward the
      breeding of scab-resistant apple cultivars. Modern apple breeding programs
      include the use of molecular markers, making it possible to combine several
      different scab-resistance genes in 1 apple cultivar (pyramiding) and to speed up
      the breeding process. The apple scab-resistance gene Vb is derived from the
      Siberian crab apple 'Hansen's baccata #2', and is 1 of the 6 "historical" major
      apple scab-resistance genes (Vf, Va, Vr, Vbj, Vm, and Vb). Molecular markers have
      been published for all these genes, except Vr. In testcross experiments conducted
      in the 1960s, it was reported that Vb segregated independently from 3 other major
      resistance genes, including Vf. Recently, however, Vb and Vf have both been
      mapped on linkage group 1, a result that contrasts with the findings from former
      testcross experiments. In this study, simple sequence repeat (SSR) markers were
      used to identify the precise position of Vb in a cross of 'Golden Delicious'
      (vbvb) and 'Hansen's baccata #2' (Vbvb). A genome scanning approach, a fast
      method already used to map apple scab-resistance genes Vr2 and Vm, was used, and
      the Vb locus was identified on linkage group 12, between the SSR markers Hi02d05
      and Hi07f01. This finding confirms the independent segregation of Vb from Vf.
      With the identification of SSR markers linked to Vb, another major apple scab
      resistance gene has become available; breeders can use it to develop durable
      resistant cultivars with several different resistance genes.

PMID- 17213906
TI  - Sequence homology of polymorphic AFLP markers in garlic (Allium sativum L.).
AB  - Linkage mapping and genetic diversity studies with DNA markers in plant species
      assume that comigrating bands are identical, or at least that they have
      homologous sequences. To test this assumption in a plant with a large genome,
      sequence identities of 7 polymorphic amplified fragment length polymorphism
      (AFLP) markers of garlic, previously used to estimate similarity in genetic
      diversity studies, were characterized. Among 37 diverse garlic clones, 87 bands
      from these 7 polymorphisms were excised, amplicons were cloned, and 2 to 6
      colonies were sequenced from each band, to yield a total of 191 DNA amplicons. Of
      these 87 bands, 83 bands (95.4%) contained AFLP amplicons that were identical or
      highly homologous to the typical marker of that band; only 4 bands contained
      amplicons with little homology to the same-sized amplicons of other garlic
      clones. Of these 83 bands, 64 (73.6%) contained only highly homologous amplicons
      (>90% sequence identity), whereas 19 (21.8%) contained both homologous and
      nonhomologous amplicons, with sequence identities less than 60%. Of the 37
      nonhomologous amplicons identified, 25 (67.5%) differed in length from other
      amplicons in the band. Sequence conservation of AFLP amplicons followed patterns
      similar to phylogenetic relationships among garlic clones, making them useful for
      developing simple PCR-based markers in genetic mapping and diversity assessment.

PMID- 17213907
TI  - Genetic relationships among fruiting-mei (Prunus mume Sieb. et Zucc.) cultivars
      evaluated with AFLP and SNP markers.
AB  - Genetic relationships among 50 fruiting-mei (Prunus mume Sieb. et Zucc.)
      cultivars from China and Japan were investigated, using 767 amplified fragment
      length polymorphism (AFLP) and 103 single nucleotide polymorphism (SNP) markers.
      The polymorphism among the cultivars was found to be 69.77%, based on EcoR I +
      Mse I AFLP primer pairs. The sequence alignment of 11 group sequences, derived
      from 50 samples, yielded 103 SNPs; the total length of genomic sequences was 3683
      bp. Among these SNPs, 73 were heterozygous in the loci of different cultivars.
      The SNP distribution was 58% transition, 40% transversion, and 2% InDels. There
      was also 1 trinucleotide deletion. AFLP and SNP markers allowed us to evaluate
      the genetic diversity of these 50 fruiting-mei cultivars. The 2 derived
      cladograms did display some differences: all cultivars formed 2 subclusters (1A
      and 1B) in the cladogram based on AFLP polymorphisms, and formed 3 subclusters
      (2A, 2B, and 2C) in the cladogram based on SNP polymorphisms; and, in the
      cladogram based on AFLP polymorphisms, most cultivars from the Guangdong to
      Fujian provinces (G-F) in China, from the Yunnan, Hunan, and Sichuan provinces (Y
      S-H) in China, and from Japan grouped in cluster 1A, and 18 (78.26%) of 23
      cultivars from Jiangsu to Zhejiang provinces in China (J-Z) grouped in cluster
      1B. The results demonstrate that mei cultivars from Japan are clustered with
      cultivars from China, and support the hypothesis that mei in Japan were
      introduced from China. Cultivars from the J-Z region of China have more genetic
      similarities. Cultivars from the G-F and Y-S-H regions have fewer genetic
      similarities and suggest more germplasm exchanges in the past.

PMID- 17213908
TI  - The Tsn1-ToxA interaction in the wheat-Stagonospora nodorum pathosystem parallels
      that of the wheat-tan spot system.
AB  - The wheat tan spot fungus (Pyrenophora tritici-repentis) produces a well
      characterized host-selective toxin (HST) known as Ptr ToxA, which induces
      necrosis in genotypes that harbor the Tsn1 gene on chromosome 5B. In previous
      work, we showed that the Stagonospora nodorum isolate Sn2000 produces at least 2
      HSTs (SnTox1 and SnToxA). Sensitivity to SnTox1 is governed by the Snn1 gene on
      chromosome 1B in wheat. SnToxA is encoded by a gene with a high degree of
      similarity to the Ptr ToxA gene. Here, we evaluate toxin sensitivity and
      resistance to S. nodorum blotch (SNB) caused by Sn2000 in a recombinant inbred
      population that does not segregate for Snn1. Sensitivity to the Sn2000 toxin
      preparation cosegregated with sensitivity to Ptr ToxA at the Tsn1 locus. Tsn1
      disrupted mutants were insensitive to both Ptr ToxA and SnToxA, suggesting that
      the 2 toxins are functionally similar, because they recognize the same locus in
      the host to induce necrosis. The locus harboring the tsn1 allele underlies a
      major quantitative trait locus (QTL) for resistance to SNB caused by Sn2000, and
      explains 62% of the phenotypic variation, indicating that the toxin is an
      important virulence factor for this fungus. The Tsn1 locus and several minor QTLs
      together explained 77% of the phenotypic variation. Therefore, the Tsn1-ToxA
      interaction in the wheat-S. nodorum pathosystem parallels that of the wheat-tan
      spot system, and the wheat Tsn1 gene serves as a major determinant for
      susceptibility to both SNB and tan spot.

PMID- 17213909
TI  - Analysis of sugarcane mosaic virus resistance in maize in an isogenic dihybrid
      crossing scheme and implications for breeding potyvirus-resistant maize hybrids.
AB  - The gene action of 2 sugarcane mosaic virus (SCMV) resistance loci in maize,
      Scmv1 and Scmv2, was evaluated for potyvirus resistance in an isogenic
      background. All 4 homozygous and 5 heterozygous isogenic genotypes were produced
      for introgressions of the resistant donor (FAP1360A) alleles at both loci into
      the susceptible parent (F7) genetic background using simple sequence repeat
      markers. For SCMV and maize dwarf mosaic virus (MDMV), virus symptoms appeared
      rapidly in the 3 homozygous genotypes, with susceptibility alleles fixed at 1 or
      both loci. Although the 9 isogenic genotypes revealed a high level of resistance
      to Zea mosaic virus (ZeMV), the same 3 homozygous genotypes were only partially
      resistant. This indicates that 1 resistance gene alone is not sufficient for
      complete resistance against SCMV, MDMV, and ZeMV. Scmv1 showed strong early and
      complete dominant gene action to SCMV, but it gradually became partially
      dominant. Scmv2 was not detected at the beginning, showing dominant gene action
      initially and additive gene action at later stages. Both genes interacted
      epistatically (for a high level of resistance, at least 1 resistance allele at
      each of both loci is required). This implies that double heterozygotes at the 2
      loci are promising for producing SCMVresistant hybrids. Results are discussed
      with respect to prospects for isolation of SCMV and MDMV resistance genes.

PMID- 17213910
TI  - New porcine microRNA genes found by homology search.
AB  - MicroRNAs (miRNAs) repress target genes at the post-transcriptional level and
      play important roles in development and cell lineage decisions. In vertebrates,
      however, both the targets of miRNAs and their expression profiles during
      development are poorly understood. Thus far, 326 human miRNAs, 249 mouse miRNAs,
      and 195 rat miRNAs have been identified. Even though the pig is a promising
      animal model in regenerative biology, as well as in livestock production, only 54
      pig miRNAs have been identified. Here, we report the identification of 58 new pig
      miRNAs. We conducted a homology search using either human or mouse miRNAs genes
      queried against the pig genome. The new pig miRNAs consist of 23 miRNAs showing
      homology to mouse, 21 showing homology to human, and 16 showing homology to both
      human and mouse. The expression profile of 6 miRNAs were analyzed by Northern
      blot analysis isolated from porcine tissues: ovary, heart, kidney, liver, and
      pancreas.

PMID- 17213911
TI  - Genetic diversity of maize kernel starch-synthesis genes with SNAPs.
AB  - Measuring genetic diversity in populations of a crop species is very important
      for understanding the genetic structure of and subsequently improving the crop
      species by genetic manipulation. Single-nucleotide amplified polymorphisms
      (SNAPs) among and within maize populations of waxy, dent, and sweet corns at 25
      single-nucleotide polymorphism (SNP) sites in 6 kernel starch-synthesis genes
      (sh2, bt2, su1, ae1, wx1, and sh1) were determined. Because of the intensive
      selection of some favorable alleles in starch-synthesis genes during the breeding
      process, and the resultant strong linkage disequilibrium (LD), the number of
      haplotypes in each population was far less than expected. Subsequent phenetic
      clustering analysis with the SNAPs indicated that the dent, waxy, and sweet corns
      formed distinct subclusters, except in a few incidences. LD was surveyed among
      SNAPs of intragenic, intergenic, and intrachromosomal SNPs in whole and
      subpopulations, which revealed that some SNAPs showed high LD with many other
      SNAPs, but some SNAPs showed low or no significant LD with others, depending on
      the subpopulation, indicating that these starch genes have undergone different
      selection in each subpopulation during the breeding process. Because the starch
      synthesis genes used in this study are important in maize breeding, the genetic
      diversity, LD, and accessions having rare SNAP alleles might be valuable in maize
      improvement programs.

PMID- 17213912
TI  - Molecular evolution of satellite DNA repeats and speciation of lizards of the
      genus Darevskia (Sauria: Lacertidae).
AB  - Satellite DNA repeats were studied in Caucasian populations of 18 rock lizard
      species of the genus Darevskia. Four subfamilies (Caucasian Lacerta satellites
      (CLsat)I-IV) were identified, which shared 70%-75% sequence similarity. The
      distribution of CLsat subfamilies among the species was studied. All the species
      could be divided into at least 3 clades, depending on the content of CLsat
      subfamilies in each genome: "saxicola", "rudis", and "mixta" lizards. CLsatI was
      found in all studied species, but in very different quantities; the "saxicola"
      group contained this subfamily predominantly. The "rudis" group also contained
      CLsatIII, and the "mixta" group carried considerable amounts of CLsatII. The
      highest concentrations of CLsatI and CLsatII were detected in 2 ground lizards-
      D. derjugini and D. praticola, respectively. D. parvula predominantly carried
      CLsatIII. CLsatIV was found only in the Crimean species D. lindholmi. The
      distribution patterns of satellite subfamilies show possible postglacial
      speciation within the genus Darevskia. A hybrid origin of species that possess 2
      or 3 CLsat subfamilies and important clarifications to the systematics of the
      genus are proposed.

PMID- 17213913
TI  - Integration of microsatellite-based genetic maps for the turkey (Meleagris
      gallopavo).
AB  - Integration of turkey genetic maps and their associated markers is essential to
      increase marker density in support of map-based genetic studies. The objectives
      of this study were to integrate 2 microsatellite-based turkey genetic maps--the
      Roslin map and the University of Minnesota (UMN) map--by genotyping markers from
      the Roslin study on the mapping families of the UMN study. A total of 279 markers
      was tested, and 240 were subsequently screened for polymorphisms in the
      UMN/Nicholas Turkey Breeding Farms (NTBF) mapping families. Of the 240 markers,
      89 were genetically informative and were used for genotyping the F2 offspring.
      Significant genetic linkages (log of odds > 3.0) were found for 84 markers from
      the Roslin study. BLASTn comparison of marker sequences with the draft assembly
      of the chicken genome found 263 significant matches. The combination of genetic
      and in silico mapping allowed for the alignment of all linkage groups of the
      Roslin map with those of the UMN map. With the addition of the markers from the
      Roslin map, 438 markers are now genetically linked in the UMN/NTBF families, and
      more than 1700 turkey sequences have now been assigned to likely positions in the
      chicken-genome sequence.

PMID- 17213914
TI  - Identification of common root-lesion nematode (Pratylenchus thornei Sher et
      Allen) loci in bread wheat.
AB  - Plant parasitic nematodes are a major biotic cause of wheat-yield loss in
      temperate wheat-growing regions. A major strategy to develop resistance to root
      lesion nematodes (RLNs) in wheat is to assess and then exploit their natural
      genetic variation. This study examines RLN (Pratylenchus thornei) resistance in 1
      Middle Eastern landrace (AUS4930 7.2) and 1 synthetic hexaploid wheat, CROC_1/AE.
      SQUARROSA (224)//OPATA (CROC), using F2 and F9 populations generated by crossing
      AUS4930 7.2 and CROC with the susceptible cultivar Pastor, and inoculating these
      crosses with P. thornei in greenhouse trials. Wheat microsatellite markers linked
      to previously identified quantitative trait loci (QTLs) for resistance to P.
      thornei and P. neglectus were used to screen both populations. In the AUS4930 7.2
      x Pastor population, resistance loci on chromosomes 1B, 2B, and 6D were detected.
      Similarly, in the CROC x Pastor population, 2 resistance loci, located on
      chromosomes 1B and 3B, were identified. Interestingly, a resistance locus located
      on chromosome 6D was not detected. More detailed mapping is required in these 2
      populations, developed using new RLN resistance sources, to determine whether the
      QTLs identified on these chromosomes are the same, are allelic, or are linked to
      different resistance loci from those previously identified, and to determine
      whether these 2 sources contain other novel resistance loci.

PMID- 17213922
TI  - A look at molecular nanosized magnets from the aspect of inter-molecular
      interactions.
AB  - Nanosized molecular magnetic materials such as single-molecule magnets and single
      chain magnets are recent attractive research targets in the fields of materials
      chemistry and physics, not only because of their fundamental fascination, but
      also because of their potential applications as ultimate memory devices or in
      quantum computations. In this paper, we give our personal perspectives on these
      materials. In particular "magnetic assemblies of single-molecule magnets", in
      which inter-molecular interaction is an essential factor in determining their
      properties, will be focused on together with related compounds reported recently.

PMID- 17213923
TI  - Rhodium diphosphite pincer complexes. Rare preferred in-plane olefin conformation
      in square-planar compounds.
AB  - Square-planar ethylene rhodium derivatives bearing pincer diphosphite ligands
      have been prepared and characterized, they display a rare in-plane coordination
      which, based on DFT calculations, has been mainly attributed to steric effects.

PMID- 17213924
TI  - From discrete [Y(DMF)8][Cu4(mu3-I)2(mu-I)3I2] ion pairs to extended
      [Y(DMF)6(H2O)2][Cu7(mu4-I)3(mu3-I)2(mu-I)4(I)]1infinity and
      [Y(DMF)6(H2O)3][Cu(I)7Cu(II)2(mu3-I)8(mu-I)6]2infinity arrays by H-bond
      templating in a confined solvent-free environment.
AB  - An ionic heterometallic species [Y(DMF)(8)][Cu(4)(micro(3)-I)(2)(micro
      I)(3)I(2)](1) was isolated from a solution of CuI, NH(4)I and YI(3)(Pr(i)OH)(4)
      in DMF-isopropoxyethanol, and was converted in a confined environment by
      progressive substitution of the DMF ligands with water molecules first into a 1D
      zig-zag structure [Y(DMF)(6)(H(2)O)(2)][Cu(7)(micro(4)-I)(3)(micro(3)-I)(2)(micro
      I)(4)(I)](1infinity)(2) and finally into a 2D sheet
      [Y(DMF)(6)(H(2)O)(3)][Cu(I)(7)Cu(II)(2)(micro(3)-I)(8)(micro-I)(6)](2infinity)(3)
      by H-bond templating.

PMID- 17213921
TI  - Randomized dose-ranging controlled trial of AQ-13, a candidate antimalarial, and
      chloroquine in healthy volunteers.
AB  - OBJECTIVES: To determine: (1) the pharmacokinetics and safety of an
      investigational aminoquinoline active against multidrug-resistant malaria
      parasites (AQ-13), including its effects on the QT interval, and (2) whether it
      has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans.
      DESIGN: Phase I double-blind, randomized controlled trials to compare AQ-13 and
      CQ in healthy volunteers. Randomizations were performed at each step after
      completion of the previous dose. SETTING: Tulane-Louisiana State University
      Charity Hospital General Clinical Research Center in New Orleans. PARTICIPANTS:
      126 healthy adults 21-45 years of age. INTERVENTIONS: 10, 100, 300, 600, and
      1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13.
      OUTCOME MEASURES: Clinical and laboratory adverse events (AEs), pharmacokinetic
      parameters, and QT prolongation. RESULTS: No hematologic, hepatic, renal, or
      other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache,
      lightheadedness/dizziness, and gastrointestinal (GI) tract-related symptoms were
      the most common AEs. Although symptoms were more frequent with AQ-13, the numbers
      of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13
      and CQ, respectively: headache, 17/63 and 10/63, p = 0.2;
      lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63;
      p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was
      cleared more rapidly than CQ (respectively, median oral clearance 14.0-14.7 l/h
      versus 9.5-11.3 l/h; p < or = 0.03). QTc prolongation was greater with CQ than AQ
      13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus
      AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no
      arrhythmias or other cardiac AEs with either AQ-13 or CQ. CONCLUSIONS: These
      studies revealed minimal differences in toxicity between AQ-13 and CQ, and
      similar linear pharmacokinetics.

PMID- 17213925
TI  - Asymmetric self-assembly with atmospheric CO2 fixation of a pentanuclear
      carbonate NiI) complex based on dissimilar building blocks.
AB  - Formation in basic solution of an asymmetric pentanuclear carbonate Ni(II)
      complex with a compartmental ligand involves atmospheric CO(2) uptake, either by
      reaction of two slightly different dinuclear precursors that yield its di- and
      trinuclear "building blocks", or directly, by spontaneous self-organization of
      metal and ligand starting reactants.

PMID- 17213926
TI  - The reactions of dialkylgallium hydrides with tert-butylethynylbenzenes--a
      systematic investigation into the course of hydrogallation reactions.
AB  - The reactions of bis- and tris(tert-butylethynyl)benzenes with dialkylgallium
      hydrides afforded two different types of products. 1,4-Di(tert
      butylethynyl)benzene and dialkylgallium hydrides R(2)GaH bearing relatively small
      substituents (R = Et, nPr) gave the expected addition products with each C triple
      bond C triple bond inserted into a Ga-H bond. The intact GaR(2) groups are
      attached to those carbon atoms which are in alpha-position to the benzene rings,
      and intermolecular Ga-C interactions led to the formation of one-dimensional
      coordination polymers. In contrast secondary reactions with the release of the
      corresponding trialkylgallium derivatives GaR(3) (R = Et, nPr, iPr, CH(2)tBu,
      tBu) were observed for all hydrogallation reactions involving the trisalkyne
      1,3,5-tris(tert-butylethynyl)benzene. A similar reaction was observed upon
      treatment of the 1,4-bisalkyne with a dialkylgallium hydride bearing a relatively
      bulky substituent (R = neopentyl). Cyclophane type molecules are formed in all
      these cases with two or three gallium atoms in the bridging positions between
      both benzene rings.

PMID- 17213927
TI  - Preparing alpha,beta-unsaturated Fischer-type carbene complexes via an unforeseen
      route.
AB  - Four 4-(NH-amino)-1-metalla-1,3-diene carbene complexes, two of which contain
      novel 4-membered heterometallacycles, formed regioselectively from the reaction
      of a mixture of [(CH(3))(2)(CH(3)S)S][BF(4)], the acetonitrilium electrophile,
      CH(3)CNCH(3)(+), and the deprotonated alkoxycarbene complexes,
      (CO)(5)M=C(OCH(3))CH(2)Li (M = Cr, W). The preferred Z-configurations of the
      alkoxy and amino groups are determined by strong H-bonding in the products. The
      metal-carbene bonds in the chelates are shorter by 0.08 A than those in the
      acyclic compounds.

PMID- 17213928
TI  - Non-covalent polymerisation in the solid state: halogen-halogen vs. methyl-methyl
      interactions in the complexes of 2,4-di(2-pyridyl)-1,3,5-triazine ligands.
AB  - Fe(II), Co(II), Ni(II) and Cu(II) complexes based on the triazine ligand 2,4
      di(2'-pyridyl)-6-(p-bromo-phenyl)-1,3,5-triazine have been synthesised and
      characterised. The electrochemical, magnetic and spectroscopic properties of the
      complexes have also been investigated, and the electron deficient triazine ligand
      has been shown to affect each of these properties. Further investigation of solid
      state structures of the ligand and its Fe(II), Co(II) and Cu(II) complexes has
      established that stabilising Br-Br interactions exist which link neighbouring
      molecules to form one-dimensional tapes. A slight modification of the ligand,
      i.e., using 2,4-di(2'-pyridyl)-6-(p-methylphenyl)-1,3,5-triazine, in which the
      phenyl substituent has changed from a bromine to a methyl group, eliminates the
      one-dimensional tape and gives rise to significant pi-stacking interactions in
      the solid state.

PMID- 17213929
TI  - Transition metal complexes with wide-angle dithio-, diseleno- and
      ditelluroethers: properties and structural systematics.
AB  - The ligands o-C(6)H(4)(CH(2)EMe)(2) (E = S or Se) have been prepared and
      characterised spectroscopically. A systematic study of the coordination chemistry
      of these, together with the telluroether analogue, o-C(6)H(4)(CH(2)TeMe)(2), with
      late transition metal centers has been undertaken. The planar complexes [MCl(2){o
      C(6)H(4)(CH(2)SMe)(2)}] and [M{o-C(6)H(4)(CH(2)EMe)(2)}(2)](PF(6))(2) (M = Pd or
      Pt; E = S or Se), the distorted octahedral [RhCl(2){o-C(6)H(4)(CH(2)EMe)(2)}(2)]Y
      (E = S or Se: Y = PF(6); E = Te: Y = Cl) and [RuCl(2){o
      C(6)H(4)(CH(2)EMe)(2)}(2)] (E = S, Se or Te), the dithioether-bridged binuclear
      [{RuCl(2)(p-cymene)}(2){micro-o-C(6)H(4)(CH(2)SMe)(2)}] and the tetrahedral [M'{o
      C(6)H(4)(CH(2)EMe)(2)}(2)]BF(4) (M' = Cu or Ag; E = S, Se or Te) have been
      obtained and characterised by IR and multinuclear NMR spectroscopy ((1)H, (63)Cu,
      (77)Se{(1)H}, (125)Te{(1)H} and (195)Pt), electrospray MS and microanalyses.
      Crystal structures of the parent o-C(6)H(4)(CH(2)SMe)(2) and seven complexes are
      described, which show three different stereoisomeric forms for the chelated
      ligands, as well as the first example of a bridging coordination mode in
      [{RuCl(2)(p-cymene)}(2){micro-o-C(6)H(4)(CH(2)SMe)(2)}]. These studies reveal the
      consequences of the sterically demanding o-xylyl backbone, which typically leads
      to unusually obtuse E-M-E chelate angles of approximately 100 degrees .

PMID- 17213930
TI  - Comparative study of donor atom effects on the thermodynamic and electron
      transfer kinetic properties of copper(II/I) complexes with sexadentate
      macrocyclic ligands. [CuII/I([18]aneS4N2)] and [CuII/I([18]aneS4O2)].
AB  - Studies have been conducted on the copper complexes formed with two sexadentate
      macrocyclic ligands containing four thioether sulfur donor atoms plus either two
      nitrogen or two oxygen donor atoms on opposing sides of the ring. The resulting
      two ligands, L, designated as [18]aneS(4)N(2) and [18]aneS(4)O(2), respectively,
      represent homologues of the previously studied Cu(ii/i) system with a macrocycle
      having six sulfur donor atoms, [18]aneS(6). Crystal structures of
      [Cu(II)([18]aneS(4)O(2))](ClO(4))(2) and [Cu(I)([18]aneS(4)O(2))]ClO(4) have been
      determined in this work. Comparison of the structures of all three systems
      reveals that the oxidized complexes are six coordinate with two coordinate bonds
      undergoing rupture upon reduction. However, the geometric changes accompanying
      electron transfer appear to differ for the three systems. The stability constants
      and electrochemical properties of both of the heteromacrocyclic complexes have
      been determined in acetonitrile and the Cu(II/I)L electron-transfer kinetics have
      been studied in the same solvent using six different counter reagents for each
      system. The electron self-exchange rate constants have then been calculated using
      the Marcus cross relationship. The results are compared to other Cu(II/I)L
      systems in terms of the effect of ligand geometric changes upon the overall
      kinetic behavior.

PMID- 17213931
TI  - Five-coordinate Pd(II) orthometallated triarylphosphite complexes.
AB  - The reaction of the orthopalladated triarylphosphite complexes [{Pd(mu
      Cl){kappa(2)-P,C-P(OC(6)H(2)-2,4-R(2))(OC(6)H(3)-2,4-R(2))}(2)] (R = H, (t)Bu)
      with bis(2-diphenylphosphinoethyl)phenylphosphine leads to a five-coordinate
      palladium(II) (R = H) and a mixture containing four-and five-coordinate species
      (R = (t)Bu). The crystal structure of the five-coordinate species [Pd{kappa(2)
      P,C-(P(OC(6)H(4))(OC(6)H(5))(2)}{bis(2
      diphenylphosphinoethyl)phenylphosphine}][SbF(6)] is presented. This complex
      reacts with hydrogen peroxide or [AuCl(tht)] to give four-coordinate complexes in
      which the displaced phosphine residue is either oxidised or coordinated to gold
      chloride; this demonstrates that the five-coordinate complexes are labile in
      solution. By contrast, the reactions of the dimeric precursors with 1,1,1
      tris(diphenylphosphinomethyl)ethane give four-coordinate complexes in the solid
      state, although evidence is presented that the smaller phosphite-containing
      system is five-coordinate at room temperature or higher in solution.

PMID- 17213932
TI  - Dicopper(II) complexes of a new pyrazolate-containing Schiff-base macrocycle and
      related acyclic ligand.
AB  - Dicopper(II) complexes of two new 3,5-disubstituted-pyrazole-based ligands,
      bis(quadridentate) macrocyclic ligand (L1)(2-) and bis(terdentate) acyclic ligand
      (L2)(-), were synthesised by Schiff base condensation of 3,5-diformylpyrazole and
      either one equivalent of 1,3-diaminopropane or two equivalents of 2-(2
      aminoethyl)pyridine in the presence of one or two equivalents of copper(II) ions,
      respectively. Copper(II) acetate monohydrate was employed in the synthesis of
      [Cu(2)(L1)(OAc)(2)], [Cu(2)(L2)(H(2)O)(2)(OAc)(3)] and [Cu(II)(2)(L1)(NCS)(2)];
      in the last of these one equivalent of NaNCS per copper(II) ion was also added.
      The fourth complex, [Cu(2)(L2)(NCS)(2)(DMF)]BF(4), was prepared using copper(II)
      tetrafluoroborate hexahydrate, along with two equivalents of NaOH and six of
      NaSCN. All four of these dimetallic complexes have been characterised by single
      crystal X-ray diffraction: the two macrocyclic complexes are the first such
      Schiff base complexes to be so characterised. A feature common to all four of the
      structures is bridging of the two copper(II) centres by the pyrazolate
      moiety/moieties. The structure determinations show that the coordination mode of
      the acetate groups in both [Cu(2)(L1)(OAc)(2)].2MeOH.H(2)O and
      [Cu(2)(L2)(H(2)O)(2)(OAc)(3)] is unidentate as had been tentatively predicted by
      analysis of the infrared spectra (DeltaOCO of 199 and 208 cm(-1), respectively).
      The magnetochemical studies of the macrocyclic complexes, over the temperature
      range 4-300 K, revealed strong antiferromagnetic coupling with J = -169 and -213
      cm(-1) for [Cu(2)(L1)(OAc)(2)].2H(2)O and [Cu(II)(2)(L1)(NCS)(2)].DMF
      respectively. The J values have been discussed in relation to a published
      correlation involving the CuN(pyrazolate)N(pyrazolate) angles.

PMID- 17213933
TI  - Tripodal borate ligands from tris(dimethylamino)borane: the first synthesis of a
      chiral tris(methimazolyl)borate ligand, and the crystal structure of a single
      diastereomer pseudo-C3-symmetric Ru(II) complex.
AB  - The activation of tris(dimethylamino)borane towards reaction with a chiral
      methimazole by N-methylimidazole has been used to prepare the first example of a
      chiral tris(methimazolyl)borate ligand. Coordination of this neutral ligand to
      Ru(II) has been achieved by reaction with [(p-cymene)RuCl(2)](2) to provide a
      single diastereomer complex in which the chirality of the methimazolyl
      substituents dictate the chirality of the bicyclo[3.3.3]cage formed by the ligand
      on coordination to the metal. The alternative approach to chiral
      tris(methimazolyl)borate ligands involving the introduction of a chiral group
      onto the boron atom has been explored by replacing N-methylimidazole in the above
      reaction by chiral oxazolines as activating bases in reaction with simple
      methimazole. However, although the B(NMe(2))(3) is activated to reaction with
      methimazole by these oxazolines, an intramolecular oxazoline ring-opening by a
      coordinated methimazolyl sulfur occurs and prevents the successful synthesis of
      these ligands.

PMID- 17213934
TI  - A spin-frustrated star-shaped heterotetranuclear CrIIIMnII3 species and its
      magnetic and HF-EPR measurements.
AB  - A tetranuclear complex [Cr(III)Mn(II)(3)(PyA)(6)Cl(3)] 1 containing pyridine-2
      aldoximato monoanion, PyA, has been structurally and magnetochemically
      characterized. The compound is a rare example of a tetranuclear star-shaped metal
      topology containing pyridine-2-aldoximato ligands. Static magnetic studies have
      demonstrated very weak antiferromagnetic exchange interactions between the
      paramagnetic centers (S(Cr) = 3/2 and S(Mn) = 5/2) resulting in closely spaced
      low-lying levels, which undergo splitting and crossing. Preliminary high-field
      EPR measurements (20 < nu < 388 GHz) indicate the presence of zero-field
      splitting D of the order of 0.7 cm(-1).

PMID- 17213935
TI  - Insertion of CO2 into a palladium allyl bond and a Pd(II) catalysed carboxylation
      of allyl stannanes.
AB  - The complex 2,6-bis[(di-t-butylphosphino)methyl]phenyl allyl palladium
      (PCP(tBu)Pd-allyl, 3) reacts with CO(2) in a very fast insertion reaction to give
      the corresponding butenoate complex. The reaction is thought to occur via a
      cyclic six-membered transition state (7), where the gamma-carbon of the allyl
      group is linked up with the CO(2)-carbon. A group of related PCP complexes were
      investigated as catalysts for the carboxylation of tributyl(allyl)stannane. A
      catalytic cycle is proposed for this reaction where the rate determining step is
      the transmetallation between tin and palladium. The carboxylation reaction is
      faster using less sterically crowded catalysts whereas the electron richness of
      the palladium complexes seems less important for reactivity. Thus, there was no
      apparent difference in reactivity between 2,6-bis[(di
      phenylphosphino)methyl]phenyl palladium triflouroacetate (13) and
      resorcinolbis(diphenyl)phosphinite palladium triflouroacetate (10). Both of these
      complexes give high turnovers for the carboxylation of tributyl(allyl)stannane
      (80% in 16 h using a ca. 5% catalyst loading and 4 atm CO(2) pressure). On the
      other hand complex 3 was inactive in the catalytic carboxylation reaction.

PMID- 17213939
TI  - The impact of domestic wood burning on personal, indoor and outdoor levels of 1,3
      butadiene, benzene, formaldehyde and acetaldehyde.
AB  - The aim of this study was to quantify personal exposure and indoor levels of the
      suspected or known carcinogenic compounds 1,3-butadiene, benzene, formaldehyde
      and acetaldehyde in a small Swedish town where wood burning for space heating is
      common. Subjects (wood burners, n = 14), living in homes with daily use of wood
      burning appliances were compared with referents (n = 10) living in the same
      residential area. Personal exposure and stationary measurements indoors and at an
      ambient site were performed with diffusive samplers for 24 h. In addition, 7 day
      measurements of 1,3-butadiene and benzene were performed inside and outside the
      homes. Wood burners had significantly higher median personal exposure to 1,3
      butadiene (0.18 microg m(-3)) compared with referents (0.12 microg m(-3)), which
      was also reflected in the indoor levels. Significantly higher indoor levels of
      benzene were found in the wood-burning homes (3.0 microg m(-3)) compared with the
      reference homes (1.5 microg m(-3)). With regard to aldehydes, median levels
      obtained from personal and indoor measurements were similar although the four
      most extreme acetaldehyde levels were all found in wood burners. High
      correlations were found between personal and indoor levels for all substances
      (r(s) > 0.8). In a linear regression model, type of wood-burning appliance,
      burning time and number of wood replenishments were significant factors for
      indoor levels of 1,3-butadiene. Domestic wood burning seems to increase personal
      exposure to 1,3-butadiene as well as indoor levels of 1,3-butadiene and benzene
      and possibly also acetaldehyde. The cancer risk from these compounds at exposure
      to wood smoke is, however, estimated to be low in developed countries.

PMID- 17213936
TI  - Gadolinium(III) complexes of mono- and diethyl esters of monophosphonic acid
      analogue of DOTA as potential MRI contrast agents: solution structures and
      relaxometric studies.
AB  - Two new macrocyclic DOTA-like chelates containing one phosphonate pendant arm
      were synthesised as potential contrast agents for MRI (magnetic resonance
      imaging). The chelates bind to the lanthanide(III) in an octadentate manner, via
      four nitrogen atoms, three carboxylate and one phosphonate oxygen atoms. Solution
      structures of [Ln(do3ap(OEt2))(H(2)O)] and [Ln(do3ap(OEt))(H(2)O)](-) were
      studied using (31)P and (1)H NMR spectroscopy and SAP (square-antiprismatic)/TSAP
      (twisted square-antiprismatic) isomerism was observed. Depending on the nature of
      the lanthanide(III) ion, the lanthanide(III) complexes of H(4)do3ap(OEt) are
      present in solution as up to four different diastereoisomers observable with NMR.
      The TSAP isomer is the most abundant at the beginning of the lanthanide series
      and, with a decrease of the ionic radius of lanthanide(III) ions, both TSAP and
      SAP forms were observed. A second interconversion (SAP<-->TSAP') becomes
      important at the end of the series (TSAP' means the TSAP species without a
      coordinated water molecule). The remaining axial coordination site is occupied by
      one water molecule for the Gd(3+)-complex. The calculated fraction of the TSAP
      isomer in the gadolinium(III) complexes increases in the order [Gd(DOTA)(H(2)O)](
      ) < [Gd(do3ap(OEt2))(H(2)O)] < [Gd(do3ap(OEt))(H(2)O)](-) < [Gd(do3ap)(H(2)O)](2
      ). Gadolinium(III) complexes of phosphorus-containing chelates, generally, have
      the advantage of a relatively fast water exchange rate due to a greater sterical
      demand of the phosphorus acid moiety and of the presence of the second-sphere
      water shell, which also contributes to the overall relaxivity. The
      [Gd(do3ap(OEt2))(H(2)O)] and [Gd(do3ap(OEt))(H(2)O)](-) complexes were studied by
      variable-temperature (17)O NMR and (1)H NMRD. The experimental data were
      evaluated simultaneously with commonly used equations based on Solomon
      Bloembergen-Morgan approximation, extended by a contribution of the second
      coordination sphere. The water exchange rates were found to be strongly dependent
      on the TSAP/SAP isomeric ratio and the overall charge of the complex: the
      monoanionic [Gd(do3ap(OEt))(H(2)O)](-) complex with TSAP molar fraction equal to
      0.36 has the water exchange rate of 20 x 10(6) s(-1) (tau(M) = 50 ns) while
      neutral [Gd(do3ap(OEt2))(H(2)O)] complex with TSAP molar fraction 0.28 has an
      exchange rate equal to 4.4 x 10(6) s(-1) (tau(M) = 227 ns).

PMID- 17213940
TI  - A near real-time system for continuously monitoring airborne subtilisin-type
      enzymes in the industrial atmosphere.
AB  - We describe the development and validation of a portable system comprising an air
      sampler coupled to an automated flow injection analysis device. The system is
      able to monitor airborne concentrations of subtilisin-type enzymes in the
      workplace atmosphere on a continuous basis. Sampling is in two stages: using a
      sampling head that is designed to mimic human respiration at approx. 1 m s(-1) at
      a sampling rate of 600 l min(-1). In the second stage, the captured particles are
      deposited by impaction from the air stream onto the inner surface of a cyclone
      that is continuously washed with a jet of buffer solution. Deposited particles
      are then washed into a reservoir from which samples are taken every 5-6 min and
      injected automatically into a continuous flow injection analysis system.
      Proteolytic enzyme in the sample passes through a bioreactor maintained at about
      40 degrees C. This contains a cellulose solid phase matrix on which is covalently
      immobilised Texas Red-labelled gelatin as substrate. The passing enzyme partially
      digests the substrate releasing fluorophore that is detected down stream in a
      flow cell coupled to a fluorimeter. The system is calibrated using enzyme
      standards and the intensity of the resulting peaks from the ex-air samples is
      converted to airborne concentrations using a mathematical model programmed into a
      PC. The system has a limit of detection of 4.8 ng m(-3) and a dynamic range of 5
      60 ng m(-3). The within assay precision (RSD) is 6.3-9.6% over this range. The
      within batch precision is 20.3% at 20 ng m(-3) and the corresponding between
      batch value is 19.5%. The system has been run for periods up to 8 h in the
      laboratory and for up to 4 h at a factory site and the values obtained compared
      with time-averaged values obtained from a conventional Galley sampler and in
      house analysis when reasonable agreement of the results was observed. The
      stability of the system over 21 days of continuous use with standards injected
      periodically was studied. Linearity was observed for all the standard plots
      throughout. At the end of 21 days, after a total exposure equivalent to 2395 ng
      ml(-1) of Savinase, the signal due to the 5.0 ng ml(-1) standard was still easily
      detectable.

PMID- 17213941
TI  - Comparative evaluation of a bioluminescent bacterial assay in terrestrial
      ecotoxicity testing.
AB  - Despite the widespread and successful use of luminescence-based bioassays in
      water testing, their applications to soils and sediments is less proven. In part
      this is because such bioassays have mainly been carried out in an aqueous-based
      medium and, as such, favour contaminants that are readily water-soluble. In this
      study, aqueous solutions and soils contaminated with heavy metals (HM), polar
      organic contaminants and hydrophobic organic contaminants (HOCs) were tested
      using a range of luminescence-based bioassays (Vibrio fischeri, Escherichia coli
      HB101 pUCD607 and Pseudomonas fluorescens 10586r pUCD607). For the first two
      chemical groups, the assays were highly reproducible when optimised extraction
      procedures were employed but for HOCs the bioassay response was poor.
      Quantitative structure-activity relationships (QSARs) obtained from aqueous
      solutions had a linear response although correlation for the chemicals tested
      using bacterial bioassays was significantly less sensitive than that of sublethal
      tests for Tetrahymena pyriformis. Bacterial and Dendrobaena veneta bioassay
      responses to extracts from HM amended soils showed that a clear relationship
      between trophic levels could be obtained. There is no doubt that the wide range
      of bioluminescent-based bioassays offers complementary applications to
      traditional testing techniques but there is a significant need to justify and
      optimise the extraction protocol prior to application.

PMID- 17213942
TI  - A small subsurface ion mobility spectrometer sensor for detecting environmental
      soil-gas contaminants.
AB  - A small subsurface ion mobility spectrometer (SS-IMS) was constructed and tested
      with several environmental contaminants to determine its potential for monitoring
      gaseous volatile organic compounds in the vadose zone. Trichloroethylene (TCE)
      and tetrachloroethylene (PCE) were detected and separated in IMS for the first
      time. Detection limits as low as 1 part per billion volume-to-volume (ppb(v))
      were observed. Reduced mobility (K(0)) values were reported for 11 environmental
      contaminants. These data demonstrated the potential of ion mobility spectrometry
      as a viable technology for detecting and separating environmental soil-gas
      contaminants in the field, which may lead to a practical and simple approach for
      long-term monitoring of contaminated soils.

PMID- 17213943
TI  - Detection of sulfur-free odorants in natural gas using ion mobility spectrometry.
AB  - Beside the primary motivation of the public gas suppliers for odorizing natural
      gas with a sulfur-free odorant, which relates to the image of the environment
      friendly fuel, natural gas, competing with low-sulfur heating fuel and diesel, a
      question of crucial importance of how to detect such sulfur-free odorants comes
      up. Concerning the replacement of sulfur-containing by sulfur-free odorization,
      the availability of a fast and sensitive detection method that can, further, be
      used on-site plays a key role. The minimum concentration of the new sulfur-free
      odorant Gasodor S-Free (S-Free) in natural gas should be added at a level of at
      least 8.8 mg m(-3) to assure a significant warning smell. Therefore, a dynamic
      range between 0 and approx. 25 mg m(-3) must be realised in the rather complex
      matrix of natural gas. By means of a handheld ion mobility spectrometer, the
      odorant content in natural gas is determined within less than 80 s total analysis
      time directly at the gas pipe. The concentration of S-Free is monitored between 4
      and 23 mg m(-3) respecting the quality of the natural gas (high- and low-caloric
      gas). Results of the validation using a gas chromatograph as a reference standard
      will be discussed in detail.

PMID- 17213944
TI  - Modelling and mapping of copper runoff for Europe.
AB  - A predictive runoff rate model for copper has been refined and used to generate
      copper runoff maps for Europe. The new model is based on laboratory and field
      runoff data and expresses the runoff rate R (g m(-2) yr(-1)) through two
      contributions, both with a physical meaning: R = (0.37SO(0.5)(2) = 0.96 rain10(
      0.62 pH) (cos(theta)/cos(45 degree)). Input parameters are the SO(2)
      concentration (microg m(-3)), pH, amount of rain (mm yr(-1)), and surface angle
      of inclination (theta). The first contribution originates from dry periods
      between rain events (the first-flush effect) and the second from the rain events.
      The dry term has been refined in comparison to the original model by assuming a
      mass balance between measured corrosion mass loss, calculated copper retention in
      the patina and predicted copper runoff. The refined model predicts 76% of all
      reported runoff rates, worldwide, within 35% from their measured value. This
      includes sites with low SO(2) concentration, where the original model erroneously
      predicted higher runoff rates than corrosion rates. Based on environmental data
      from the EMEP programme for the years 1980-2000, the new model has been used to
      derive runoff rate maps for Europe with 50 x 50 km grid resolution. The runoff
      mapping shows a substantial reduction in runoff rate over the investigated time
      period, and with copper runoff rates now generally less than 2 g m(-2) yr(-1).

PMID- 17213946
TI  - A low cost method to estimate dissolved reactive phosphorus loads of rivers and
      streams.
AB  - Concentration of dissolved reactive phosphorus ([DRP]) in rivers changes
      periodically (daily, weekly, seasonally) and is dependent on the weather and
      discharge Q. Accordingly, accurate estimation of the annual DRP load requires
      intensive sampling if not even continuous monitoring, which is laborious and
      expensive. We present a new, elaborated low cost technique based on passive
      samplers (P-traps), describing their design and chemical analysis. P-traps use
      iron(oxy)hydroxide as a sorbent, are inexpensive, easy to handle, and can be
      exposed for several months. We compare average DRP concentrations obtained from
      spot samples and P-traps and discuss the applicability and accuracy of the
      suggested method to measure annual P loads of rivers characterized by highly
      variable DRP concentrations.

PMID- 17213945
TI  - Metal release from stainless steel particles in vitro-influence of particle size.
AB  - Human inhalation of airborne metallic particles is important for health risk
      assessment. To study interactions between metallic particles and the human body,
      metal release measurements of stainless steel powder particles were performed in
      two synthetic biological media simulating lung-like environments. Particle size
      and media strongly influence the metal release process. The release rate of Fe is
      enhanced compared with Cr and Ni. In artificial lysosomal fluid (ALF, pH 4.5),
      the accumulated amounts of released metal per particle loading increase
      drastically with decreasing particle size. The release rate of Fe per unit
      surface area increases with decreasing particle size. Compared with massive sheet
      metal, fine powder particles (<4 microm) show similar release rates of Cr and Ni,
      but a higher release rate of Fe. Release rates in Gamble's solution (pH 7.4), for
      all powders investigated, are significantly lower compared to ALF. No clear trend
      is seen related to particle size in Gamble's solution.

PMID- 17213947
TI  - Dielectrophoretic separation of Bacillus subtilis spores from environmental
      diesel particles.
AB  - Isolation of pathogenic bacteria from non-biological material of similar size is
      a vital sample preparation step in the identification of such organisms,
      particularly in the context of detecting bio-terrorist attacks. However, many
      detection methods are impeded by particulate contamination from the environment
      such as those from engine exhausts. In this paper we use dielectrophoresis--the
      induced motion of particles in non-uniform fields--to successfully remove over
      99% of diesel particulates acquired from environmental samples, whilst letting
      bacterial spores of B. subtilis pass through the chamber largely unimpeded. We
      believe that such a device has tremendous potential as a precursor to a range of
      detection methods, improving the signal-to-noise ratio and ultimately improving
      detection rates.

PMID- 17213948
TI  - Detection of airborne Legionella while showering using liquid impingement and
      fluorescent in situ hybridization (FISH).
AB  - Aerosols of water contaminated with Legionella bacteria constitute the only mode
      of exposure for humans. However, the prevention strategy against this pathogenic
      bacteria risk is managed through the survey of water contamination. No
      relationship linked the Legionella bacteria water concentration and their
      airborne abundance. Therefore, new approaches in the field of the metrological
      aspects of Legionella bioaerosols are required. This study was aimed at testing
      the main principles for bioaerosol collection (solid impaction, liquid
      impingement and filtration) and the in situ hybridization (FISH) method, both in
      laboratory and field assays, with the intention of applying such methodologies
      for airborne Legionella bacteria detection while showering. An aerosolization
      chamber was developed to generate controlled and reproducible L. pneumophila
      aerosols. This tool allowed the identification of the liquid impingement method
      as the most appropriate one for collecting airborne Legionella bacteria. The
      culturable fraction of airborne L. pneumophila recovered with the liquid
      impingement principle was 4 and 700 times higher compared to the impaction and
      filtration techniques, respectively. Moreover, the concentrations of airborne L.
      pneumophila in the impinger fluid were on average 7.0 x 10(5) FISH-cells m(-3)
      air with the fluorescent in situ hybridization (FISH) method versus 9.0 x 10(4)
      CFU m(-3) air with the culture method. These results, recorded under well
      controlled conditions, were confirmed during the field experiments performed on
      aerosols generated by hot water showers in health institutions. This new approach
      may provide a more accurate characterization of aerobiocontamination by
      Legionella bacteria.

PMID- 17213949
TI  - Effect of fasting on the pattern of urinary arsenic excretion.
AB  - Millions of people in some of the poorest regions of the world are exposed to
      high levels of arsenic through drinking contaminated water. It has been reported
      that development of cancer caused by arsenic exposure in such populations is
      dependent on dietary and nutritional factors which can modulate arsenic
      metabolism. Many people in arsenic exposed regions of Bangladesh and India
      practice fasting for at least one month every year when they refrain from
      consumption of food and fluid during daylight hours. How such practices may
      modulate arsenic metabolism has not been previously investigated. This study
      investigated this issue by determining total arsenic and its species in urine
      samples from a group of 29 unexposed volunteers at the beginning of the fasting
      and at the end of approximately 12 h of fasting period. Inductively coupled
      plasma mass spectrometry (ICP-MS) and high performance liquid chromatography
      (HPLC) coupled with ICP-MS was used to measure the total arsenic and arsenic
      speciation in the urine samples, respectively. The mean total levels of arsenic
      at the beginning of fasting (18.3 microg g(-1) creatinine) and at the end of
      approximately 12 h of fasting (17.7 microg g(-1) creatinine) did not differ
      significantly (p > 0.05). However, the percentages of urinary arsenic as the
      methylated arsenic species methylarsonate (MA) were found to be significantly
      different (p < 0.05) and this species was observed more frequently at the end of
      fasting, although its overall concentration was similar. There were no
      significant differences (p > 0.05) in both the concentrations and percentages of
      other urinary arsenic species detected, namely arsenobetaine (AB) and
      dimethylarsinate (DMA). Arsenite (As(III)) and arsenate (As(V)) were also
      analyzed, but were not detected. We conclude that fasting for a period of 12 h
      results in a significant increase in the percentage of urinary arsenic as MA, and
      its frequency of detection in the volunteers at the end of the fasting period is
      almost nine fold higher. This suggests that metabolism of arsenic is altered by
      fasting.

PMID- 17213951
TI  - Application of FT-IR for assessment of the biological stability of landfilled
      municipal solid waste (MSW) during in situ aeration.
AB  - Disposal of untreated municipal solid waste leads to gaseous emissions as well as
      liquid degradation products. In situ aeration is an emerging means for
      remediation of abandoned landfills. It aims at an accelerated mineralization and
      stabilization of waste organic matter and thus reduces significantly the emission
      potential of the site. In order to prove the success of the technique, evaluation
      of the biological stability of the aerated material has been suggested. Fourier
      Transform Infrared Spectroscopy (FT-IR) provides comprehensive information on the
      chemical composition of solid waste samples. Different stages of organic matter
      degradation are reflected by changes in the infrared spectral pattern. In the
      present study the feasibility of applying FT-IR for assessment of the stability
      of waste material derived from abandoned landfills and for in situ aeration
      process control was investigated. Waste samples derived in the course of pilot
      scale and lab-scale aeration experiments were characterized by FT-IR (4000-400
      cm(-1), KBr-technique, transmission mode) and a set of conventional parameters
      describing biological stability. The occurrence of distinct indicator bands was
      correlated with chemical and biological waste properties using 206 solid waste
      samples. Visual spectra interpretation was found to be appropriate in proving a
      reduced emission potential of initially rather reactive waste (respiration
      activity over 4 days (RA(4)) > 7 mg O(2) g(-1) DM) during aeration. Furthermore,
      cluster analysis was applied successfully to differentiate between original and
      aerated waste samples, even for rather stable material (RA(4) < 7 mg O(2) g(-1)
      DM), when visual spectra interpretation was limited.

PMID- 17213950
TI  - Combining passive sampling and toxicity testing for evaluation of mixtures of
      polar organic chemicals in sewage treatment plant effluent.
AB  - Effluent from sewage treatment plants has been associated with a range of
      pollutant effects. Depending on the influent composition and treatment processes
      the effluent may contain a myriad of different chemicals which makes monitoring
      very complex. In this study we aimed to monitor relatively polar organic
      pollutant mixtures using a combination of passive sampling techniques and a set
      of biochemistry based assays covering acute bacterial toxicity (Microtox),
      phytotoxicity (Max-I-PAM assay) and genotoxicity (umuC assay). The study showed
      that all of the assays were able to detect effects in the samples and allowed a
      comparison of the two plants as well as a comparison between the two sampling
      periods. Distinct improvements in water quality were observed in one of the
      plants as result of an upgrade to a UV disinfection system, which improved from
      24x sample enrichment required to induce a 50% response in the Microtox assay to
      84x, from 30x sample enrichment to induce a 50% reduction in photosynthetic yield
      to 125x, and the genotoxicity observed in the first sampling period was
      eliminated. Thus we propose that biochemical assay techniques in combination with
      time integrated passive sampling can substantially contribute to the monitoring
      of polar organic toxicants in STP effluents.

PMID- 17213953
TI  - Influence of substrate conformation on the deglycosylation of ribonuclease B by
      recombinant yeast peptide:N-glycanase.
AB  - Peptide:N-glycanase has been thought to be responsible for proteasome-dependent
      degradation of misfolded glycoproteins translocated from the endoplasmic
      reticulum (ER) to the cytosol. Therefore, the enzyme was supposed to be able to
      distinguish between native and non-native glycoproteins. In the present study, a
      recombinant, yeast peptide:N-glycanase, Png1p, was expressed in Escherichia coli
      as inclusion bodies and was purified, refolded and characterized. The results
      showed that the recombinant enzyme has a broad pH range adaptation, from pH 4.0
      to pH 10.0, and has an optimum temperature of 30 degrees C. This enzyme is a zinc
      metalloenzyme. Its activity was abolished with the addition of EDTA and not
      restored by adding metal ions. Furthermore, the deglycosylation efficiency of
      recombinant Png1p from E. coli was investigated with respect to the substrate
      conformation in vitro. When ribonuclease B (RNase B) was denatured at 60-65
      degrees C or by 40-60 mM dithiothreitol, indicated by its obvious structural
      change and sharpest activity change, its deglycosylation by Png1p was most
      prominent. The deglycosylation efficiency of RNase B by Png1p was found to be
      related to its structural conformation and enzymatic activity.

PMID- 17213952
TI  - Enamel matrix derivative stimulates osteogenesis- and chondrogenesis-related
      transcription factors in C3H10T1/2 cells.
AB  - Our purpose was to determine how enamel matrix derivative (EMD) affects the
      expression of osteogenesis- and chondrogenesis-related transcription factors in
      undifferentiated mesenchymal cells. C3H10T1/2 cell line, a typical pluripotential
      mesenchymal cell line, was cultured with or without EMD for up to 7 d. Expression
      of mRNAs encoding osteogenesis- and chondrogenesis-related transcription factors
      (Runx2, Osterix, AJ18, Dlx5, Msx2, Sox5, Sox9 and Zfp60) was measured using real
      time polymerase chain reaction. Runx2 and Sox9 protein expression and the
      presence of bone morphogenetic protein (BMP)-6-like molecules in EMD were
      determined by Western blotting. EMD substantially increased mRNA levels of
      osteogenesis- and chondrogenesis-related transcription factors. EMD also induced
      Runx2 and Sox9 protein expression. Western blotting analysis of EMD using anti
      BMP-6 antibody revealed immunoreactive bands corresponding to about 14 kDa and 60
      kDa. These results suggest that EMD stimulates osteogenesis- and chondrogenesis
      related transcription factors, and these activities may be mediated, at least in
      part, by BMP-6 in EMD.

PMID- 17213954
TI  - Huntingtin cleavage induced by thrombin in vitro.
AB  - Huntingtin (Htt) mutation causes Huntington's disease. Sequence analysis of Htt
      revealed a possible thrombin cleavage site in the N-terminal region of Htt. In
      order to investigate if thrombin can cleave Htt, we expressed the N-terminal
      fragment (1-969) of wild-type (wt) Htt (Htt 1-969) in MCF-7 cells and studied its
      cleavage pattern by thrombin in vitro. An expression plasmid pcDNA3-Htt-18Q-969
      was used to transfect MCF-cells and Htt 1-969 expression was confirmed with
      immunofluorescence. Cell lysates were incubated with thrombin (1 U/ml, 10 U/ml,
      and 30 U/ml) for 1 h in the presence or absence of hirudin, a thrombin inhibitor.
      Htt fragments were separated by sodium dodecylsulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and detected with anti-Htt antibodies. An Htt fragment
      with molecular mass of approximately 80 kDa was produced after incubation with
      thrombin. The size of this Htt fragment was anticipated by molecular mass
      generated from thrombin-mediated cleavage at the amino acid 183 in the Htt.
      Production of an 80 kDa fragment was inhibited by hirudin. This study provides
      the first evidence that Htt is cleaved by thrombin in vitro at amino acid 183. If
      endogenous thrombin cleaves Htt in vivo, the physiological significance of
      thrombin-mediated cleavage of Htt should be further investigated.

PMID- 17213955
TI  - Different effects of homocysteine and oxidized low density lipoprotein on
      methylation status in the promoter region of the estrogen receptor alpha gene.
AB  - We investigated the effects of homocysteine (Hcy) and oxidized low density
      lipoprotein (ox-LDL) on DNA methylation in the promoter region of the estrogen
      receptor alpha (ERalpha) gene, and its potential mechanism in the pathogenesis of
      atherosclerosis. Cultured smooth muscle cells (SMCs) of humans were treated by
      Hcy and ox-LDL with different concentrations for different periods of time. The
      DNA methylation status was assayed by nested methylation-specific polymerase
      chain reaction, the lipids that accumulated in the SMCs and foam cell formations
      were examined with Oil red O staining. The proliferation of SMCs was assayed by
      the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The
      results showed that ox-LDL in moderate concentrations (10-40 mg/L) induced de
      novo methylation in the promoter region of the ERalpha gene of SMCs. However,
      high concentrations (50 mg/L) of ox-LDL, resulted in demethylation of ERalpha.
      The Hcy treatment resulted in de novo methylation in the promoter region of the
      ERalpha gene with a concentration- and treating time-dependent manner, and a dose
      dependent promoting effect on SMC proliferation. These data indicated that the
      two risk factors for atherosclerosis had the function of inducing de novo
      methylation in the promoter region of the ERalpha gene of SMCs. However, high
      concentrations (50 mg/L) of ox-LDL induced demethylation, indicating that
      different risk factors of atherosclerosis with different potency might cause
      different aberrant methylation patterns in the promoter region of the ERalpha
      gene. The atherogenic mechanism of Hcy might involve the hypermethylation of the
      ERalpha gene, leading to the proliferation of SMCs in atherosclerotic lesions.

PMID- 17213956
TI  - Vaccination against Schistosoma japonicum infection by DNA vaccine encoding
      Sj22.7 antigen.
AB  - To observe the in vitro expression of DNA vaccine pcDNA3-Sj22.7 and its
      immunological effect in mice, the recombinant plasmid pcDNA3-Sj22.7 was used to
      transfect HeLa cells with liposome-mediated method and the expression of Sj22.7
      mRNA and protein was examined using reverse transcription-polymerase chain
      reaction, sodium dodecylsulfate-polyacrylamide gel electrophoresis and Western
      blot. Then, the ability of pcDNA3-Sj22.7 to protect against Schistosoma japonicum
      challenge infections was analyzed according to worm reduction rate and egg
      reduction rate after vaccination of mice. The serum levels of specific IgG
      antibody and T lymphocyte proliferation response were also determined. After the
      challenge infection, Sj22.7-driven interferon (IFN)-gamma and interleukin (IL)-4
      was also quantified. Results showed that pcDNA3-Sj22.7 could express Sj22.7 mRNA
      and protein in vitro. Immunization resulted in a worm reduction rate of 29.70%,
      egg reduction rate of 47.25% (liver) and 51.73% (intestine), and egg reduction
      rate of 25.90% (eggs per female), suggesting induction of significant anti
      fecundity in the pcDNA3-Sj22.7 group. Enzyme-linked immunosorbent assay and
      Western blot analysis indicated that immunized mice generated specific IgG
      against Sj22.7. T lymphocytes from mice immunized with pcDNA3-Sj22.7 showed a
      significant proliferation response to rSj22.7. The culture of spleen cells showed
      that secretion of IFN-gamma increased but IL-4 decreased. The results indicate
      hat DNA vaccination by pcDNA3-Sj22.7 is sufficient to elicit significant levels
      of protective immunity against S. japonicum infection. The DNA vaccine could
      induce significant cellular and humoral immune response, and display predominant
      T helper cell type 1 type immune responses, which contribute to the protective
      immunity against challenge infection in mice.

PMID- 17213957
TI  - Fluorescence resonance energy transfer analysis of bid activation in living cells
      during ultraviolet-induced apoptosis.
AB  - Ultraviolet (UV) irradiation is a DNA-damaging agent that triggers apoptosis
      through both the membrane death receptor and mitochondrial apoptotic signaling
      pathways. Bid, a pro-apoptotic Bcl-2 family member, is important in most cell
      types to apoptosis in response to DNA damage. In this study, a recombinant
      plasmid, YFP-Bid-CFP, comprised of yellow and cyan fluorescent protein and a full
      length Bid, was used as a fluorescence resonance energy transfer analysis (FRET)
      probe. Using the FRET technique based on YFP-Bid-CFP, we found that Bid
      activation was initiated at 9+/-1 h after UV irradiation, and the average
      duration of the activation was 75+/-10 min. Bid activation coincided with a
      collapse of the mitochondrial membrane potential with an average duration of 50+/
      10 min. When cells were pretreated with Z-IETD-fmk (caspase-8 specific inhibitor)
      the process of Bid activation was completely inhibited, but the apoptosis was
      only partially affected. Z-DEVD-fmk (caspase-3 inhibitor) and Z-FA-fmk (non asp
      specific inhibitor) did not block Bid activation. Furthermore, the endogenous Bid
      activation with or without Z-IETD-fmk in response to UV irradiation was confirmed
      by Western blotting. In summary, using the FRET technique, we observed the
      dynamics of Bid activation during UV-induced apoptosis and found that it was a
      caspase-8 dependent event.

PMID- 17213958
TI  - Nerve growth factor prevents the apoptosis-associated increase in
      acetylcholinesterase activity after hydrogen peroxide treatment by activating
      Akt.
AB  - Acetylcholinesterase (AChE) is thought to play an important role during
      apoptosis. Our results showed that H2O2 induced AChE activity, a functional
      marker in apoptosis, increases in neuronal-like PC12 cells. Glutathione, which is
      involved in cellular redox homeostasis, inhibited the increase of AChE activity,
      suggesting that reactive oxygen species (ROS) play a key role in this process.
      Further investigation showed that the elevation of AChE was observed after the
      degradation of Akt, release of cytochrome c from mitochondria into the cytosol,
      and activation of caspase family members. When nerve growth factor (NGF) was
      present, with the maintenance of Akt level, the elevation of AChE, the cytochrome
      c diffusion, as well as apoptosis were markedly attenuated in H2O2-treated PC12
      cells. However, wortmannin, an inhibitor of the PI3K/Akt pathway, accelerated the
      apoptosis and increased the AChE activity. The overexpression of constitutively
      activated Akt, which is a downstream signalling element of the NGF receptor TrkA,
      delayed mitochondrial collapse and inhibited elevation of AChE activity. Thus,
      NGF prevented apoptosis and elevation of AChE activity by activating the Akt
      pathway and stabilizing the function of mitochondria.

PMID- 17213959
TI  - Listeria monocytogenes mutants carrying Newcastle disease virus F gene fused to
      its actA and plcB: in vitro expression and immunogenicity in chickens.
AB  - Recombinant Listeria monocytogenes mutants carrying Newcastle disease virus (NDV)
      fusion protein gene F were constructed by homologous recombination. NDV F or its
      truncated fragment Fa was used as the model heterologous gene to be integrated
      into actA or plcB downstream of their signal sequences. Correct orientation of
      the inserted genes was verified by polymerase chain reaction amplification of F
      or Fa. The inserted F and Fa were expressed in the two recombinants Lm-DeltaactA
      F and Lm-DeltaplcB-Fa as shown by sodium dodecylsulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) and western blot. Both recombinants exhibited reduced
      virulence to embryonated eggs and mice by about 1.5-2.5 logs as compared with the
      parent wild strain 10403S. They were also less invasive than strain 10403S
      (P<0.05). Chickens receiving the recombinant strains orally or intraperitoneally
      were partially protected from virulent NDV challenge possibly due to enhancement
      of non-specific immunity because the antibody titers against the homologous virus
      strain or the recombinant truncated fusion protein were marginal. Further
      research is needed in other animal models to see if the low antibody response
      results from insufficient expression of the heterologous genes as a result of
      failure of L. monocytogenes or its recombinants to persist or replicate in
      chickens.

PMID- 17213960
TI  - Differential expression of neutrophilic granule proteins between Th1 and Th2
      cells.
AB  - T helper cell type 1 (Th1) and 2 (Th2) play central roles in immune regulation.
      To identify the novel genes differentially expressed between Th1 and Th2 cells,
      CD4+ T cells were isolated from DO11.10 transgenic mice and induced under Th1 or
      Th2 conditions. Microarray showed differential expression of neutrophilic granule
      proteins (NGP) between Th1 and Th2 cells. NGP was first identified as a myeloid
      specific granule protein with homology to the cystatin superfamily. Here we
      confirmed greater expression of NGP in Th2 cells by reverse transcription
      polymerase chain reaction and real-time polymerase chain reaction analysis. We
      also showed that the expression of NGP mRNA had a peak expression after 5 d
      culture under Th2- but not Th1-biasing conditions. Antibody against NGP was
      prepared, and in concert with the results of mRNA analysis, the level of NGP
      protein in Th2 cells detected by Western blot analysis was also higher than that
      in Th1 cells. GFP-NGP fusion proteins overexpressed in HeLa cells were localized
      to the cytoplasm. These results suggest NGP is a novel marker distinguishing Th2
      from Th1 cells and maybe a novel cytokine secreted by Th2 cells.

PMID- 17213961
TI  - Hypoxia induces transforming growth factor-beta1 gene expression in the pulmonary
      artery of rats via hypoxia-inducible factor-1alpha.
AB  - The present study was undertaken to investigate the dynamic expression of hypoxia
      inducible factor-1alpha (HIF-1alpha) and transforming growth factor-beta1 (TGF
      beta1) in hypoxia-induced pulmonary hypertension of rats. It was found that mean
      pulmonary arterial pressure (mPAP) increased significantly after 7 d of hypoxia.
      Pulmonary artery remodeling index and right ventricular hypertrophy became
      evident after 14 d of hypoxia. HIF-1alpha mRNA staining was less positive in the
      control, hypoxia for 3 d and hypoxia for 7 d, but began to enhance significantly
      after 14 d of hypoxia, then remained stable. Expression of HIF-1alpha protein in
      the control was less positive, but was up-regulated in pulmonary arterial tunica
      intima of all hypoxic rats. TGF-beta1 mRNA expression in pulmonary arterial walls
      was increased significantly after 14 d of hypoxia, but showed no obvious changes
      after 3 or 7 d of hypoxia. In pulmonary tunica adventitia and tunica media, TGF
      beta1 protein staining was less positive in control rats, but was markedly
      enhanced after 3 d of hypoxia, reaching its peak after 7 d of hypoxia, and then
      weakening after 14 and 21?d of hypoxia. Western blotting showed that HIF-1alpha
      protein levels increased significantly after 7 d of hypoxia and then remained at
      a high level. TGF-beta1 protein level was markedly enhanced after 3 d of hypoxia,
      reaching its peak after 7 d of hypoxia, and then decreasing after 14 and 21?d of
      hypoxia. Linear correlation analysis showed that HIF-1alpha mRNA, TGF-beta1 mRNA,
      TGF-beta1 protein were positively correlated with mPAP, vessel morphometry and
      right ventricular hypertrophy index. TGF-beta1 protein (tunica adventitia) was
      negatively correlated with HIF-1alpha mRNA. Taken together, our results suggest
      that changes in HIF-1alpha and TGF-beta1 expression after hypoxia play an
      important role in hypoxia-induced pulmonary hypertension of rats.

PMID- 17213962
TI  - [Sonographic diagnosis of a liver abscess caused by an enterohepatic fistula in a
      patient with Crohn's disease].
AB  - Liver abscesses in patients with Crohn's disease are rare. We report on a patient
      with Crohn's disease and a liver abscess of the left lobe caused by an
      enterohepatic fistula. With treatment of antibiotics and Infliximab the abscess
      showed complete regression. Percutaneous drainage of the liver abscess was not
      performed because the abscess was shown not to be completely liquefied at echo
      enhanced ultrasound. This case report demonstrates the usefulness of percutaneous
      conventional and echo-enhanced ultrasound for the diagnosis of liver abscesses.
      Furthermore, this case also shows that enterohepatic fistulas can be diagnosed
      precisely with percutaneous ultrasound.

PMID- 17213963
TI  - Determinants of endurance exercise capacity in the heat in prepubertal boys.
AB  - The goal of this study was to identify factors which limit exercise endurance in
      hot ambient conditions in prepubertal boys. Eight healthy non-acclimatized,
      highly physically active prepubertal boys performed steady load cycling at
      approximately 65 % peak VO (2) to exhaustion in both cool (19.6 +/- 0.6 degrees
      C, 66.4 +/- 11.0 % relative humidity) and hot (31.0 +/- 0.3 degrees C, 56.9 +/-
      2.0 % relative humidity) environmental conditions. Cardiac output, oxygen uptake,
      rectal temperature (T (re)), rating of perceived exertion (RPE), blood pressure,
      and calculated arterial venous oxygen difference were obtained serially in each
      testing session, and percent dehydration was calculated from body weight loss.
      Endurance time was significantly shorter in the hot condition (29.30 +/- 6.19
      minutes versus 41.38 +/- 6.30 minutes in the cool room). No significant
      differences in circulatory markers or hydration status were observed either
      during testing or between cycling thermal conditions. Rate of rise of T (re) was
      greater during exercise in the heat, but no significant difference in T (re)
      between conditions was observed at exhaustion. Mean values of RPE were
      consistently greater during exercise in the heat, but these differences did not
      reach statistical significance. These findings support the concept that rises in
      core temperature and/or brain perception (RPE) rather than circulatory
      insufficiency may be the critical factors defining limits to exercise in the
      heat.

PMID- 17213964
TI  - Effectiveness of low-intensity endurance training.
AB  - Recent studies point to the preventive efficacy of low-intensity endurance
      training in terms of cardiovascular risk factor modification and mortality
      reduction. In addition, it is frequently recommended as a means of stimulating
      fat metabolism. It was the intention of this study to clarify if endurance
      training effectiveness remains unimpaired when exercise intensity is reduced by a
      certain amount from "moderate" to "low", but total energy expenditure held
      constant. For this purpose, 39 healthy untrained subjects (44 +/- 7 yrs, 82 +/-
      19 kg; 173 +/- 9 cm) were stratified for endurance capacity and sex and randomly
      assigned to 3 groups: "moderate intensity" (MOD, n = 13, 5 sessions per week, 30
      min each, intensity 90 % of the anaerobic threshold [baseline lactate + 1.5
      mmol/l]), "low intensity" (LOW, n = 13, 5 sessions per week, intensity 15 bpm
      below MOD, duration proportionally longer to arrive at the same total energy
      output as MOD), and control (CO, n = 13, no training). Training was conducted
      over 12 weeks and each session monitored by means of portable heart rate (HR)
      recorders. Identical treadmill protocols prior to and after the training program
      served for exercise prescription and documentation of endurance effects. VO
      (2max) improved similarly in both training groups (MOD + 1.5 ml x min (-1) x kg (
      1); LOW + 1.7 ml x min (-1) x kg (-1); p = 0.97 between groups). Compared with CO
      (- 1.0 ml x min (-1) x kg (-1)) this effect was significant for LOW (p < 0.01)
      whereas there was only a tendency for MOD (p = 0.07). However, objective criteria
      (HR (max), maximal blood lactate) indicated that a different degree of effort was
      responsible for this finding. In comparison with CO (mean decrease of 3 bpm),
      average HR during incremental exercise decreased significantly by 9 bpm (MOD, p <
      0.05 vs. CO) and 6 bpm (LOW, p = 0.26), respectively. However, there was no
      significant difference between MOD and LOW (p = 0.60), but for changes in oxygen
      uptake at the anaerobic threshold (VO (2AT)) it was observed that MOD was
      significantly more effective than CO (p = 0.048) and LOW (p = 0.04). It is
      concluded that within a middle-aged population of healthy untrained subjects,
      endurance training effectiveness might be slightly impaired when the training
      heart rate is chosen 15 bpm lower as compared to moderate intensity, but the
      total energy output held equal.

PMID- 17213965
TI  - The effect of a single aerobic training session on cognitive flexibility in late
      middle-aged adults.
AB  - Research has shown that aerobic exercise enhances cognitive function,
      specifically executive functions. This study examines the effect of acute aerobic
      exercise on cognitive flexibility - an executive function - in late middle-aged
      individuals. Fourteen men and 45 women aged 50 - 64, were randomly assigned to
      moderate exercise (60 % of heart rate reserve), moderately-intense (70 % of heart
      rate reserve) exercise, and movie-watching control groups after a maximal
      exercise test. Prior to and following the exercise or control sessions
      participants performed two cognitive tasks: the Alternate Uses assessing
      cognitive flexibility and the Digit Span Forward subtest from the Wechsler Adult
      Intelligence Scale - Revised assessing attention span. Results indicated
      significant improvement in Alternate Uses in the exercise groups but not in the
      control group. No group differences were indicated on the Digit Span. These
      results provide partial support for the benefit of acute aerobic exercise on
      cognitive flexibility.

PMID- 17213967
TI  - [Not significant--what now?].
AB  - In a statistical significance test a scientific problem is expressed by
      formulating a null hypothesis and an opposite alternative. Construction of an
      empirical decision rule usually focuses on control of the alpha-error, i.e. the
      probability of erroneously refusing the null hypothesis. Contrary to the alpha
      error, the beta-error is not controlled and in general is of unknown size. Thus
      in case of a non-significant result the validity of the null hypothesis still may
      be highly questionable. Such an unwanted outcome of an applied test the
      researcher should try to avoid by choosing an appropriate study design. In case
      it occurs nevertheless, it is advised to further evaluate the (non-significant)
      result. This can be done by calculating confidence intervals of the tested
      effects. Furthermore the p-value can be interpreted as a metric measure of
      evidence against the null hypothesis. By means of a posterior power analysis the
      probability of a significant test result is estimated under the given
      circumstances. Thus possibly the applied test--under the assumption of actual
      validity of the alternative--turns out to have had hardly a chance of rejecting
      the null hypothesis. In this case the non-significant result (pointing towards
      the null hypothesis) is relativized substantially. On the other hand a large
      power points to a small probability of a beta-error.

PMID- 17213969
TI  - [Chemotherapy for metastatic breast cancer].
AB  - Primary goals of treatment in metastatic breast cancer include prevention and
      palliation of symptoms, maintenance or improvement of quality of life and
      prolongation of survival. In order to account for the variability of clinical
      courses, treatment decisions have to be made on an individual basis. Low risk
      patients without evidence of rapid disease progression or symptomatic disease are
      mainly considered for endocrine treatment or single agent chemotherapy, whereas
      patients at higher risk with rapidly progressive or symptomatic disease are
      candidates for poly-chemotherapies. Anthracyclines are one of the most active
      group of agents and remain active after adjuvant pre-treatment. The use of
      liposomal derivatives or weekly or prolonged application can decrease the risk of
      cardiotoxicity. There is only incomplete cross-resistance between anthracyclines
      and taxanes. Taxane-based weekly or 3 weekly regimens are therefore generally
      used in anthracycline-pretreated patients. Capecitabine, gemcitabine, or
      vinorelbine constitute candidate agents after failure of anthracyclines and/or
      taxanes and may result in objective responses or disease stabilisation. Data on
      the continuation beyond third-line chemotherapy are insufficient. Decisions have
      therefore to be made on an individual basis.

PMID- 17213968
TI  - [Fluorescence diagnosis and photodynamic therapy with 5-aminolevulinic acid
      induced protoporphyrin IX in gynecology: an overview].
AB  - Fluorescence diagnosis and photodynamic therapy with 5-aminolevulinic acid
      induced protoporphyrin IX are promising new options in the diagnosis and therapy
      of diseases in a wide spectrum of medical disciplines such as urology,
      dermatology, gastroenterology, surgery, neurosurgery and gynecology. The
      techniques are based on the application of the heme biomolecule precursor 5
      aminolevulinic acid which induces the endogenous accumulation of the
      photosensitizer protoporphyrin IX in designated tissues. After external
      excitation with blue light a strong red fluorescence can be initiated
      particularly in tumorous tissues. In gynecology many studies have been performed
      evaluating the usefulness of fluorescence based detection of cervical dysplasias,
      breast cancer, endometrial diseases, ovarian cancer and endometriosis. This work
      aims on the principles of fluorescence detection as an important tool in
      biomedical optical imaging and its current status in gynecology.

PMID- 17213970
TI  - [The expert patient: medical consequences].
AB  - The expression expert patient appeared about ten years ago. It defines the role
      of patients who are actively involved in their disease management. Most clinical
      oncologists are challenged by expert patients. Patient's expertise and
      complementary medicine are closely linked. Physicians respecting expert patients
      have to find a positive attitude towards patient self aide concepts. The medical
      skill to manage expert patients is increasingly important and new tools are being
      developed for support.

PMID- 17213971
TI  - [PTHrP and bone sialoprotein as prognostic markers for developing bone metastases
      in breast cancer patients].
AB  - BACKGROUND: Bone metastases belong to the most frequent metastases in breast
      cancer. Currently there exist no serum markers which allow early detection of
      bone metastases. PATIENTS AND METHODS: 89 patients with primary breast cancer
      have been investigated for parathyroid-hormone-related peptide (PTHrP) in the
      tumour and bone sialoprotein (BSP) in the serum. Both markers have been
      correlated with classical prognostic factors and survival. RESULTS: The median
      age of the patients was 56 years. 17 of the 89 patients developed bone metastases
      and 25 died during the observation period of 5 years. PTHrP correlated
      significantly with bone metastases free survival (p = 0.0004) and overall
      survival (p = 0.0005), whereas BSP correlated only with the bone metastases free
      survival (p = 0.03). Both markers were shown to be independent prognostic factors
      for the bone metastases free survival in the multivariate analysis. PTHrP was
      also found to be an independent prognostic factor for the overall survival.
      CONCLUSION: The investigation of PTHrP could be a prognostic marker for the
      presence of bone metastases while BSP could be a marker for the early detection
      of bone metastases.

PMID- 17213972
TI  - [Treatment of overactive bladder with sodium chondroitin sulphate].
AB  - OBJECTIVE: It is not always possible to clearly differentiate the symptoms of
      overactive bladder and interstitial cystitis. A prospective randomized study was
      performed to determine whether instillation of sodium chondroitin sulphate for
      treatment of interstitial cystitis is also effective in treating overactive
      bladder. The expected benefit of this therapeutic approach in overactive bladder
      is based on the assumption that the glycosaminoglycan layer may be damaged in
      overactive bladder as well. MATERIAL AND METHODS: Patients with chronic
      overactive bladder were randomized to one of two study groups each including 41
      patients. Group A was treated with an anticholinergic agent (tolterodine), group
      B with sodium chondroitin sulphate (Uropol S). The diagnosis was established on
      the basis of a gynecologic examination and history, urodynamic testing, introital
      ultrasound, and cystoscopy. Patients were treated for 12 months. RESULTS: An
      improvement of symptoms was reported by 15/35 (43 %) of the patients in group A
      (p = 0.000) as compared with 23/32 (72 %) of the patients in group B. The
      subjective outcome was corroborated by means of urodynamic testing, number of
      pads used, voiding frequency, and nycturia (voiding diary). Quality of life
      increased significantly in both groups in the course of treatment but there was
      no significant difference between both groups. CONCLUSION: The results of the
      study presented here suggest that restoring the glycosaminoglycan layer also
      improves or cures the symptoms in patients with overactive bladder. Patients
      clearly benefit from instillation of sodium chondroitin sulphate. These results
      must be confirmed in larger studies before a wider use of this therapeutic option
      can be recommended.

PMID- 17213973
TI  - [Hospitalization, type of obstetrical clinic and anamnestic risk profile of
      pregnant women with pregestational diabetes mellitus--results of the perinatal
      registry of Lower Saxony, Germany].
AB  - INTRODUCTION: Obstetric and diabetic societies recommend an intensive care of
      pregnancies in women with pregestational diabetes, an early hospitalization in
      case of obstetric and internal complications as well as delivery in a perinatal
      center. OBJECTIVE: To evaluate the number and duration of hospitalization of
      pregnant women with pregestational diabetes in comparison with non-diabetic women
      and further more the type of clinics in which both groups were delivered. We also
      investigated if there were any differences in anamnestic risk factors in
      correlation with the type of hospital. MATERIAL AND METHODS: The data of the
      Perinatal Registry of Lower Saxony, Germany, between 1990 and 1999 were analyzed
      retrospectively. The pregnancies of 2 543 women with pregestational diabetes were
      compared with the pregnancies of 707 695 non-diabetic women. RESULTS: There was
      at least one admission to hospital in 40 % of diabetic and 18.6 % of non diabetic
      women and more than one admission in 11.9 and 3.6 %, respectively (p < 0.001).
      The number and duration of hospitalization in both groups decreased significantly
      within the observation period. 57.7 % of all hospitals performed 1 to 4 and 11 %
      of the hospitals 5 to 9 deliveries of diabetic women per year. In the group of
      pregnant women with pregestational diabetes 45 % were delivered in clinics with 1
      to 4 and 26.4 % in clinics with 5 to 9 deliveries of diabetic women per year.
      CONCLUSIONS: A higher number and duration of hospitalization was observed in the
      diabetic group, but both decreased significantly in each group during the
      observation period. No significant trend for delivering diabetic women in
      specialized high-risk units could be detected.

PMID- 17213974
TI  - [Risk factors for recurrence of vulvar intraepithelial neoplasia III (VIN III)].
AB  - OBJECTIVE: The incidence of vulvar intraepithelial neoplasia (VIN) has increased
      in the last decades. The therapy of VIN is the in toto resection. Still some
      patients develop VIN recurrence. The aim of this retrospective study is the
      identification of risk factors for VIN recurrence. MATERIAL AND METHODS: 68
      Patients with VIN III has been examined in an univariate and multivariate
      analysis for the following parameters (follow-up: median 27 months): age, HPV,
      HIV, multicentricity, resection margins (1-4 mm, 5-9 mm, > or = 10 mm). RESULTS:
      In the univariate analysis positive HPV and HIV status correlated with VIN
      recurrence. Also resection margins < 5 mm showed a significant correlation with
      VIN recurrence. Multivariate analysis demonstrated that HPV, HIV and resection
      margins < 5 mm are independent risk factors. No statistically association was
      found for age and multicentricity. CONCLUSION: The aim of VIN therapy must be the
      total resection with a negative resection margin of > or = 5 mm. HPV- and/or HIV
      positive patients have a significantly higher risk for VIN recurrence and need
      therefore an intensive follow up.

PMID- 17213975
TI  - [Breast cancer: analysis of treatment quality in Germany 2004: retrospective
      survey by Arbeitsgemeinschaft Gynakologische Onkologie (AGO)].
AB  - The Organgruppe Mamma der Arbeitsgemeinschaft Gynaekologische Onkologie (AGO)
      conducted a nationwide 3-phase analysis of the care structure and standard of
      therapy given to patients with breast cancer from 2002 (4th quarter) to 2004 (4th
      quarter). The analysis includes 1069 patients from 257 institutions; 34% with
      early breast cancer and 66% with metastatic disease. No reliable data on the
      pattern of care of these patients have been published to date in Germany. The
      extent to which national and international therapy recommendations were
      implemented in routine clinical practice was unclear. Evaluation of the data
      shows that treatment based on the guidelines is now being implemented very
      reliably in certain sectors. This is of particular relevance to the pattern of
      adjuvant treatment in early breast cancer. At that time 68 % of the patients
      received an anthracyclin based chemotherapy and in addition 18% received an
      anthracycline and taxane based chemotherapy. Participation in clinical trials
      peaked with 30% in the neoadjuvant setting. The problem with metastatic breast
      cancer is the complexity of the interdisciplinary treatment involved. The present
      analysis conducted by the AGO was the first attempt to analyse the treatment
      given to metastatic patients and to systematise the approach to treatment. The
      fundamental problem remains, irrespective of the stage of the tumour, namely that
      too few patients are treated in randomised clinical studies.

PMID- 17213976
TI  - [Surgical management of ovarian ectopic pregnancy].
AB  - Ovarian pregnancies represent a small fraction of ectopic gestations. They are
      especially feared due to their life-threatening intraabdominal hemorrhage. Pre-
      and intraoperative diagnosis is difficult. Pathogenetically ovarian pregnancy
      arises from the retention of a fertilized ovum in the ovary. General guidelines
      for the medical management are missing. In this case report, we diagnosed a
      subacute ruptured ovarian pregnancy during surgery and performed a partial
      ovarectomy via operative laparoscopy. Other therapeutic options in managing
      ovarian ectopic pregnancy will be discussed.

PMID- 17213978
TI  - [Body stalk anomaly--a case report on a rare congenital defect].
AB  - INTRODUCTION: A body stalk anomaly is a rare congenital defect. The anomaly is
      one of the anterior abdominal wall defects. It is characterized by severe clefts
      of the abdominal wall with absence of or very small, umbilical cord. CASE REPORT:
      We report on a patient in the 21st week of gestational age with the
      ultrasonographic findings of multiple fetal anomalies including a singular
      umbilical artery and an ahydramnion. She was sent to hospital for termination of
      the pregnancy. The karyotype was normal (46 XX). Ultrasonographic evaluation of
      the fetal anterior abdominal wall was impossible due to ahydramnion. Clinical
      examination showed an omphalocoele with herniation of the stomach, the small
      intestine, the liver and the spleen. A very short umbilical cord was observed
      which was attached to the omphalocoele. The lower limbs were deformed.
      Furthermore, anal atresia with an extroverted coele was found. Autopsy confirmed
      the clinical diagnosis of a body stalk anomaly. DISCUSSION: It is important to
      distinguish a body stalk anomaly from other types of anterior abdominal wall
      defects because of their prognosis and an appropriate medical management. A body
      stalk anomaly is a sporadic defect and not associated with chromosomal
      abnormalities. This congenital defect is invariably lethal.

PMID- 17213977
TI  - [Acute ovarian vein thrombosis in the third trimestre].
AB  - BACKGROUND: Ovarian vein thrombosis is a known complication in the peri- and
      postpartum phase. Its incidence is documented as 1:600 to 1:2000. Concerning
      ovarian vein thrombosis in earlier stages of pregnancy there are only very few
      case reports. CASE REPORT: We report on a woman in her third pregnancy who
      presented with acute abdominal pain in the 27th week of gestation. After a long
      car drive she felt an acute pain in the upper right abdomen which moved down to
      the right lower abdomen. On admission the obstetrical examination showed no
      pathology. There were no contractions. Clinical and sonographic examination could
      not reveal the cause of the pain. As adequate analgesia failed to relieve the
      pain, an explorative laparotomy was performed. It showed a dilated right ovarian
      vein of 3 cm diameter with a thrombus reaching the confluence to the vena cava.
      The ovarian vessels were resected and the adnectomy on the right side performed.
      Anticoagulation was initiated. There were no complications during the
      postoperative course. The pregnancy proceeded normally. After 10 days the patient
      could be dismissed in good condition. Laboratory diagnostic showed an deficiency
      in protein C. At 39 weeks of gestation a planned caesarean section was performed
      without any complications.

PMID- 17213980
TI  - [71st Annual scientific meeting of the Japanese Circulation Society.  Kobe,
      Japan. March 15-17, 2007. Program].

PMID- 17213982
TI  - [Management of emergencies].

PMID- 17213981
TI  - [A 33-year old woman with heart arrest during Cesarean section].

PMID- 17213983
TI  - [Resistant tuberculosis increasing among HIV-infected in South Africa].

PMID- 17213984
TI  - Immunology of Diabetes IV. Progress in our understanding. Proceedings of the 8th
      Meeting of the Immunology of Diabetes Society. October 6-9, 2005. Awaji Island,
      Japan.

PMID- 17213985
TI  - Cellular and molecular mechanisms of drugs of abuse and neurotoxicity: cocaine,
      GHB, and substituted amphetamines. Proceedings of a meeting. August 16-19, 2005.
      Venice, Italy.

PMID- 17213986
TI  - Proceedings of the 9th Annual Meeting of the Society of Biotherapeutic
      Approaches. December 3, 2005. Tokyo, Japan.

PMID- 17213995
TI  - Re: Henschler R, Brennscheidt U, Mertelsmann R, and Herrmann F (1991). Induction
      of c-jun expression in the myeloid leukemia cell line KG-1 by 1-beta-D
      arabinofuranosylcytosine.

PMID- 17213996
TI  - Rethinking the cardiac helix: a structure/function journey. From bench to
      bedside. Proceedings of the Tenth RESTORE Meeting. April 9, 2005. San Francisco,
      California, USA.

PMID- 17213997
TI  - Circulating nucleic acids in plasma and serum IV. Proceedings of the Fourth
      International Conference on Circulating Nucleic Acids in Plasma/Serum. September
      4-6, 2005. London, United Kingdom.

PMID- 17213998
TI  - A tale of two surveys. Polls find divergent consumer opinions on EHRs.

PMID- 17213999
TI  - IHI campaign draws more fire. Article questions methodology, rapid-response
      teams.

PMID- 17214000
TI  - UMDNJ hit with double whammy. Institution faces separate whistle-blower lawsuits.

PMID- 17214001
TI  - [Norwegian medical education also in Uppsala].

PMID- 17214003
TI  - Proportionate response?

PMID- 17214002
TI  - Quick fix or cure-all?

PMID- 17214004
TI  - Square 100.

PMID- 17214005
TI  - Back to life.

PMID- 17214006
TI  - Why every child matters.

PMID- 17214007
TI  - Outside the box. Inspiration can be found in unexpected places.

PMID- 17214008
TI  - The bigger picture. People with mental health conditions will be actively
      consulted.

PMID- 17214010
TI  - This life. I knew I had to get a job. I had to prove to myself that I was
      recovering. Interview by Suzy Johnston.

PMID- 17214011
TI  - Looking through users' eyes.

PMID- 17214012
TI  - Fashion industry and eating disorders.

PMID- 17214013
TI  - [Virtual colonoscopy in colon neoplasms].

PMID- 17214014
TI  - A comparative review of periodontal and peri-implant soft tissue. Part 1.

PMID- 17214015
TI  - Use of chlorine dioxide mouthrinse as the ultrasonic scaling lavage reduces the
      viable bacteria in the generated aerosols.

PMID- 17214016
TI  - Cruelty's rewards: the gratifications of perpetrators and spectators.
AB  - Cruelty is the deliberate infliction of physical or psychological pain on other
      living creatures, sometimes indifferently, but often with delight. Though cruelty
      is an overwhelming presence in the world, there is no neurobiological or
      psychological explanation for its ubiquity and reward value. This target article
      attempts to provide such explanations by describing three stages in the
      development of cruelty. Stage 1 is the development of the predatory adaptation
      from the Palaeozoic to the ethology of predation in canids, felids, and primates.
      Stage 2, through palaeontological and anthropological evidence, traces the
      emergence of the hunting adaptation in the Pliocene, its development in early
      hominids, and its emotional loading in surviving forager societies. This
      adaptation provides an explanation for the powerful emotions - high arousal and
      strong affect - evoked by the pain-blood-death complex. Stage 3 is the emergence
      of cruelty about 1.5 million years ago as a hominid behavioural repertoire that
      promoted fitness through the maintenance of personal and social power. The
      resulting cultural elaborations of cruelty in war, in sacrificial rites, and as
      entertainment are examined to show the historical and cross-cultural stability of
      the uses of cruelty for punishment, amusement, and social control. Effective
      violence prevention must begin with perpetrators, not victims. If the upstream
      approaches to violence prevention advocated by the public-health model are to be
      effective, psychologists must be able to provide violence prevention workers with
      a fine-grained understanding of perpetrator gratifications. This is a distasteful
      task that will compel researchers to interact with torturers and abusers, and to
      acknowledge that their gratifications are rooted in a common human past. It is
      nonetheless an essential step in developing effective strategies for the primary
      prevention of violence.

PMID- 17214017
TI  - Language and life history: a new perspective on the development and evolution of
      human language.
AB  - It has long been claimed that Homo sapiens is the only species that has language,
      but only recently has it been recognized that humans also have an unusual pattern
      of growth and development. Social mammals have two stages of pre-adult
      development: infancy and juvenility. Humans have two additional prolonged and
      pronounced life history stages: childhood, an interval of four years extending
      between infancy and the juvenile period that follows, and adolescence, a stage of
      about eight years that stretches from juvenility to adulthood. We begin by
      reviewing the primary biological and linguistic changes occurring in each of the
      four pre-adult ontogenetic stages in human life history. Then we attempt to trace
      the evolution of childhood and juvenility in our hominin ancestors. We propose
      that several different forms of selection applied in infancy and childhood; and
      that, in adolescence, elaborated vocal behaviors played a role in courtship and
      intrasexual competition, enhancing fitness and ultimately integrating
      performative and pragmatic skills with linguistic knowledge in a broad faculty of
      language. A theoretical consequence of our proposal is that fossil evidence of
      the uniquely human stages may be used, with other findings, to date the emergence
      of language. If important aspects of language cannot appear until sexual
      maturity, as we propose, then a second consequence is that the development of
      language requires the whole of modern human ontogeny. Our life history model thus
      offers new ways of investigating, and thinking about, the evolution, development,
      and ultimately the nature of human language.

PMID- 17214018
TI  - [Effects of soil moisture on the compensation effect of winter wheat with its
      partial roots cut off at returning green stage].
AB  - The study with pot experiment showed that after cutting partial roots at
      returning green stage, the growth of winter wheat was restrained at early growth
      stage, and the leaf area was decreased significantly from returning green to
      jointing stage but restored to the level of the control at flowering stage. Under
      high soil moisture condition, root cutting increased the values of chlorophyll
      fluorescence parameters ETR, phiPS II , qp and qn, at jointing stage
      significantly. The accumulated dry matter weight per stem after anthesis was
      significantly higher in root-cut wheat (0. 81 g) than in the control (0. 56 g) ,
      with the accumulation coefficient (AC) of root-cut wheat increased by 38. 79% ,
      but no significant difference was observed in root weight. Under low soil
      moisture condition, there were no significant differences in the values of
      chlorophyll fluorescence parameters and accumulated dry matter weight per stem
      after anthesis between root-cut wheat and the control, but the root weight of
      root-cut wheat decreased significantly. Soil moisture didn' t enhance the
      compensation effect of the aboveground biomass and grain yield of root-cut wheat.
      Root cutting reduced the water consumption of winter wheat significantly. Under
      high soil moisture condition, root-cut wheat saved 2 000 ml of water, and its
      water use efficiency (WUE) ( 1. 97 g x kg (-1)) was significantly higher than
      that of the control (1.70 g x kg(-1)). Under low soil moisture condition, root
      cut wheat saved 1500 ml of water, but there was no significant difference in the
      WUE between root-cut wheat and the control.

PMID- 17214019
TI  - [Rhizodeposition and its role in carbon cycling in plant-soil system].
AB  - Rhizodeposition is an important interface process of the exchange between plant
      and soil, and plays an important role in soil carbon turnover. The
      rhizodeposition of carbon is also the bridge linking plant, soil" and
      microorganisms. This paper reviewed the researches on the rhizodeposition in
      carbon balance and carbon cycling, expounded the mechanisms of carbon
      rhizodeposition, and discussed the problems in related experiments, the
      differences of rhizodeposition with plant species, cultivars and growth stages,
      the relationships between rhizodeposition and soil respiration, and the
      significance of rhizodeposition in the carbon cycling in plant-soil system. Some
      related research tasks in the future were also proposed.

PMID- 17214020
TI  - Evaluation of the effect of endometriosis on oocyte quality and endometrial
      environment by comparison of donor and recipient outcomes following embryo
      transfer in a shared oocyte program.
AB  - PURPOSE: To determine whether endometriosis has an effect on the uterine
      environment vs the oocyte itself. METHODS: A retrospective study comparing
      pregnancy outcome of infertile donors sharing oocytes with donor egg recipients
      according to whether the donor or recipient had endometriosis or not was carried
      out. RESULTS: There were 26 transfers from donors with endometriosis vs 144 in
      donors without endometriosis. The clinical and viable PRs and implantation rates
      were 42.9%, 38.1%, and 29.4% for the endometriosis group vs 60.9%, 51.9%, and
      33.2%, respectively, for donors without endometriosis (p = NS). The clinical and
      viable PRs and implantation rates for donors with endometriosis per ET was 41.2%,
      35.3%, and 20.4% vs 50.4%, 48.0% and 28.4% for donors without endometriosis,
      respectively (p = NS). CONCLUSIONS: Though no significant differences were found
      in donors with or without endometriosis in any parameters, there did appear to be
      a trend for lower PRs and implantation rates in women undergoing controlled
      ovarian hyperstimulation.

PMID- 17214021
TI  - Fertilization by intracytoplasmic sperm injection (ICSI) does not impair
      subsequent pregnancy outcome following frozen embryo transfer (ET) as determined
      by a large retrospective analysis.
AB  - PURPOSE: To determine if fertilization by intracytoplasmic sperm injection (ICSI)
      adversely affects pregnancy outcome following frozen embryo transfer (ET).
      METHODS: Retrospective analysis of frozen ETs where the oocytes were fertilized
      by conventional insemination vs ICSI was carried out. RESULTS: No difference in
      pregnancy outcome was found in women up to age 42. There was a non-significant
      trend for lower pregnancy rates in women age 43 and older. CONCLUSIONS: In the
      largest series to date by far these data convincingly show that fertilization by
      ICSI does not impair outcome following frozen ET.

PMID- 17214022
TI  - Holiday Cheer.

PMID- 17214023
TI  - When living wills become health hazards.

PMID- 17214024
TI  - Bibliography. Current world literature. Ocular manifestations of systemic
      disease.

PMID- 17214025
TI  - The AIDS Drug Assistance Program. Following the epidemic: past, present, and
      future.

PMID- 17214026
TI  - Pressure gradient response after alcohol septal ablation in hypertrophic
      obstructive cardiomyopathy.

PMID- 17214027
TI  - [From the work of the cradle to family planning: women and associations in Aix-en
      Provence from 1901 to 1970].

PMID- 17214029
TI  - [Walter Sonntag -- an SS doctor on trial].

PMID- 17214028
TI  - Evidence of multiple hepatitis virus infections in autopsied materials of
      intravenous drug addicts.
AB  - Injection of illicit drugs is an important risk factor for acquiring parenterally
      transmitted viral infections. To investigate the prevalence of viral mono- and co
      infections in intravenous drug uses (IDUs) postmortem and to evaluate the risk of
      potential infection to personnel involved in medicolegal practice a total number
      of 59 known IDUs were tested during necropsy for serological markers of hepatitis
      B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) as
      well as for the nucleic acids of the hepatitis B and C viruses, and the GB virus
      C (GBV-C), in blood and in the liver. Our findings showed that 90.2% cases were
      positive for at least one or more serological markers of the tested viruses.
      Seroprevalence rates of anti-HCV, HBsAg and anti-HIV were 78.4%, 32.4% and 29.7%
      respectively. Of the IDUs tested for serological infection markers 43.2% were
      positive for one, 40.5% for two and 5.4% for all three markers. Viral nucleic
      acids were detected in the sera of 64.4% and in the liver of 81.4% of the cases.
      HCV, RNA, GBV-C RNA and HBV DNA were found in 33.9%, 28.8% amd 28.8% of the serum
      samples and in 67.8%, 35.6% and 28.8% of the liver tissue, respectively. Active
      viral co-infections or triple infections were detectable in the sera of 20.3% and
      in the liver of 39% of the case. Results show that the sensitivity of viral
      nucleic acid testing postmortem strongly depends on the quality and source of
      material used.

PMID- 17214030
TI  - [The space of death: the origins of extra-urban cemeteries].

PMID- 17214031
TI  - [Politics, medicine, religion, and society in the 18th-century debate on
      burials].

PMID- 17214032
TI  - [Nonsteroidal anti-inflammatory agents and the risk of actinic keratosis and
      squamous cell carcinoma].

PMID- 17214033
TI  - [The living and the dead in 18th-century Europe].

PMID- 17214034
TI  - Wisconsin and the great Spanish flu epidemic of 1918.

PMID- 17214036
TI  - Meriwether Lewis and his son: the claim of Joseph Desomet Lewis and the problem
      of history.

PMID- 17214035
TI  - [Purity of blood and nobility in colonial Mexico: the formation of a noble lore,
      1571-1700].

PMID- 17214037
TI  - [The office of the civil engineer of Pisa and its archive].

PMID- 17214038
TI  - [Which death do we die? Heinrich Bullinger's "Report of the ill." (1535)].

PMID- 17214039
TI  - "Unnatural fathers and vixen daughters": a case of incest, San Diego, California,
      1894.

PMID- 17214040
TI  - [The museum can rightly be called the medical Hermitage].

PMID- 17214041
TI  - Notes and documents: recollections of a Lincoln County doctor.

PMID- 17214042
TI  - Nevada among the states: converging public policies.

PMID- 17214043
TI  - Corinne Allen and post-manifesto antipolygamy.

PMID- 17214044
TI  - The company doctor: promoting stability in Eastern Utah mining towns.

PMID- 17214045
TI  - Bibliography of Joseph Andorfer Ewan (1909-1999).

PMID- 17214046
TI  - Reconstructing the geographical framework of the 1901 census of Canada.

PMID- 17214047
TI  - Erratum to "Inequity of upper gastrointestinal cancer distribution and survival
      with socioeconomic deprivation: a population-based study".

PMID- 17214048
TI  - Comparison of the manual stimulation test and the nonstress test: a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate manual fetal stimulation (MST) through the maternal
      abdomen in comparison to standard nonstress test (NST) in terms of nonreactive
      rates and testing time. MATERIAL AND METHOD: Five hundred and forty high-risk
      singleton pregnancies at 28 gestational weeks or more were assigned to have
      either NST or MST using blocked randomization (270 each). All fetal heart rate
      (FHR) tracings were analyzed blindly using standard NST criteria by one
      perinatologist. RESULTS: The MST group provided a significantly higher reactive
      rate than that of the NST group, 98.9% and 84.4% respectively, p < 0.001. Mean
      testing time of the reactive results of the MST group was also significantly
      shorter than that of the NST group, 7.94 +/- 6.27 min and 13.91 +/- 9.58 min
      respectively, p < 0.001. CONCLUSION: This is the first randomized controlled
      trial (RCT) to demonstrate the distinctive benefit of the simple and less
      expensive MST. MST significantly reduces the time to reactivity and increases the
      frequency of reactivity when compared to NST alone.

PMID- 17214049
TI  - Effectiveness of ginger for prevention of nausea and vomiting after gynecological
      laparoscopy.
AB  - OBJECTIVE: To study the effectiveness of ginger for prevention of nausea and
      vomiting after gynecological laparoscopy. MATERIAL AND METHOD: From July 2005 to
      October 2005, 60 inpatients who underwent laparoscopic operations for non-cancer
      gynecologic conditions at Bangkok Metropolitan Administration Medical College or
      Vajira Hospital were randomized into Group A (n = 30) or Group B (n = 30). Group
      A received 3 capsules of ginger (1 capsule contained 0.5 g of ginger powder)
      while Group B received 3 capsules of placebo. Both groups received their medicine
      1 hour prior the operation. Nausea and vomiting were assessed with the Visual
      Analogue Scores (VAS) and presence of vomiting at 2 and 6 hours after the
      operation. RESULTS: Median VAS at 2 hours post operation of Group A was not
      significantly different from that of Group B with the median of 0 (range, 0-5.4)
      and 0.15 (range, 0-10) respectively (95% CI from -2.59 to 0.90 and p = 0.142). At
      6 hours post operation, the median VAS of Group A was significantly lower than
      group B, 0.55 (range, 0-7.4) versus 2.80 (range, 0-10) (95% CI from -3.61 to 
      0.73 and p = 0.015). Presence of vomiting at 2 hours was not different between
      the two groups, 10% in Group A and 20% in Group B (95% CI from -28% to 8% and p =
      0.278). At 6 hours, 23.3% of group A had an episode of vomiting compared to 46.7%
      of group B (95% CI from -47% to 1% and p = 0.058). CONCLUSION: Ginger has shown
      efficacy for prevention of nausea and borderline significance to prevention
      vomiting after gynecological laparoscopy at 6 hour post operation.

PMID- 17214050
TI  - Appropriateness of antibiotic prophylaxis in gynecologic surgery at Srinagarind
      Hospital.
AB  - OBJECTIVE: To evaluate the rate of appropriate prophylactic antibiotic use in
      gynecologic surgery at Srinagarind Hospital. DESIGN STUDY: Prospective
      descriptive study. SETTING: Srinagarind Hospital, Khon Kaen University, Thailand.
      MATERIAL AND METHOD: Medical records of 250 women who had undergone gynecologic
      surgery at Srinagarind Hospital during August 2004 and February 2005 were
      evaluated. The criteria of appropriate prophylactic antibiotics were based on
      ACOG recommendation 2001. Data on demographic information, surgery procedure and
      antibiotic use during surgery were extracted from these medical records and
      analyzed. MAIN OUTCOMES: Rate of appropriate prophylactic antibiotic use and type
      of inappropriate use. RESULTS: Two hundred and fifty women had undergone
      gynecologic surgery during the study period. There were 168 total abdominal
      hysterectomy (TAH), 12 vaginal hysterectomy (VH), 30 salpingooophorectomy (SO), 3
      myomectomy, 30 diagnostic laparoscopy and 7 laparoscopic ovarian cystectomy
      (LOC). Twenty private staff and twenty residents conducted these operations. The
      overall rate of appropriate prophylactic antibiotic use was 75.2% (95% CI 69.28
      80.33). Main type of inappropriate use were multiple doses and indication not
      fulfilled. The overall rate of appropriate antibiotic prophylaxis among surgeries
      conducted by private staff was 53.19% (95% CI 42.66-63.46) and the overall rate
      of appropriate antibiotic prophylaxis among surgeries conducted by residents was
      88.46% (95% CI 82.13-93.83). The rate of early post operative infection between
      both groups was not different (p = 0.529). There was no drug complication in all
      subjects. CONCLUSION: The overall rate of appropriate antibiotic prophylaxis in
      gynecologic surgery at Srinagarind Hospital was 75.2% (95% CI 69.28-80.33).
      Residents used prophylactic antibiotics more appropriately than private staff.

PMID- 17214051
TI  - Vitrification of mouse oocyte using open pulled straws compared with needles.
AB  - OBJECTIVE: To compare the survival rate of mouse oocytes and fertilization rate
      between using open pulled straws (OPS) and needles for vitrification. MATERIAL
      AND METHOD: Meiosis II oocytes from female C57B/6J mice aged 7-8 weeks were
      collected and allocated to two groups for vitrification by using OPS or needles.
      Vitrified oocytes were thawed, morphological survival and fertilization rate were
      examined. RESULTS: There was no obvious difference between the morphological
      survival rates of vitrified mouse oocytes using OPS and needles (66.7% vs 64.8%).
      Proportions Difference 1.9% (95% CI -7.1, 10.7). The vitrified oocytes from the
      needle had significantly higher percentages of fertilization rate than OPS (76.8%
      vs 62.5%). Proportions Difference -14.3% (95% CI -24.5, -3.6). CONCLUSION:
      Vitrification method of mouse oocytes using needles when compared to OPS provides
      a similar morphological survival rate and higher fertilization rate.

PMID- 17214052
TI  - Inflammatory markers and conventional atherosclerotic risk factors in acute
      ischemic stroke: comparative study between vascular disease subtypes.
AB  - BACKGROUND: Large vessel atherosclerosis and small vessel disease are two major
      causes of ischemic stroke. In patients with large vessel disease, the lesions can
      be located in the extracranial carotid or intracranial arteries. OBJECTIVE: To
      search for the differences of risk factors and inflammatory markers among
      patients with each subtype of vascular disease. MATERIAL AND METHOD: Patients
      with acute ischemic stroke who had large vessel atherosclerosis or small vessel
      disease were studied. Patients with large vessel atherosclerosis were subdivided
      into extracranial carotid and intracranial stenosis groups. Blood samples were
      collected for c-reactive protein, erythrocyte sedimentation rate, hemoglobin A1C
      fibrinogen, fasting plasma glucose, cholesterol, triglyceride, and low-density
      and high-density lipoproteins. Risk factors and results of the blood tests
      between the groups of patients were compared. RESULTS: There were 116 patients in
      the study. Sixty-three patients had large vessel disease, whereas 53 patients had
      small vessel disease. More prevalence of diabetes and higher c-reactive protein
      were significantly found in patients with large vessel disease. C-reactive
      protein on admission was also higher in patients with extracranial carotid
      stenosis than those with intracranial stenosis. Serum cholesterol and low-density
      lipoprotein was significantly higher in patients with intracranial stenosis than
      those with small vessel extracranial disease. CONCLUSION: Diabetes and higher c
      reactive protein on admission were associated with large vessel disease. c
      reactive protein was also higher in patients with extracranial carotid stenosis
      but their cholesterol and low-density lipoprotein were significantly lower than
      those with intracranial disease.

PMID- 17214053
TI  - Isolated antibody to hepatitis B core antigen in HIV-1 infected patients and a
      pilot study of vaccination to determine the anamnestic response.
AB  - BACKGROUND: Isolated antibody to hepatitis B core antigen (anti-HBc) is
      frequently found in HIV-infected patients. The present study aimed to determine
      the prevalence and risk factors of isolated anti-HBc and the anamnestic response
      to hepatitis B vaccination in this population. MATERIAL AND METHOD: HIV-infected
      patients who visited Ramathibodi Hospital in May 2006 were included to test
      hepatitis B serology. Subjects with isolated anti-HBc were given hepatitis B
      vaccine and tested for anti-HBs. RESULTS: Of 140 patients, 28 (20%) had isolated
      anti-HBc. From multivariate analysis, IVDU (OR 30.8, p < 0.001) and anti-HCV
      seropositive (OR 6.7, p = 0.002) were independent risk factors for isolated anti
      HBc. Two from 28 (7%) patients who received vaccine had a response to
      vaccination. CONCLUSION: Prevalence of isolated anti-HBc among Thai HIV-infected
      patients was 20%. Risk factors of isolated anti-HBc were IVDU and anti-HCV
      seropositive. Anamnestic response to hepatitis B vaccination was low. Further
      study with strategies to improve the response of vaccination is needed.

PMID- 17214054
TI  - Nontuberculous mycobacterial infections in King Chulalongkorn Memorial Hospital.
AB  - BACKGROUND: Nontuberculous mycobacteria (NTM) can cause infections in both human
      immunodeficiency virus (HIV)-infected and HIV-noninfected patients. The incidence
      of NTM infections has been increasing since the acquired immunodeficiency
      syndrome (AIDS) epidemics. However, the epidemiologic and clinical data of NTM
      infections in Thailand are limited. OBJECTIVE: Determine the epidemiology,
      clinical manifestations, treatment, and outcome of NTM infections in King
      Chulalongkorn Memorial Hospital from January 2000 to December 2003. MATERIAL AND
      METHOD: One hundred and fourteen patients had positive NTM cultures; however,
      complete medical records were available in only 103 (90.3%) patients. RESULTS:
      There were 71 (68.9%) HIV-infected patients, and 38 (87%) of them had the CD4
      counts of < 200 cells/microL (range 4-360). Among HIV-infected patients, the most
      common previous opportunistic infections included tuberculosis (36.6%),
      Pneumocystis jirovecii pneumonia (25.3%), cryptococcal meningitis (15.5%),
      penicilliosis (5.6%), and cytomegalovirus infection (5.6%). Most patients
      presented with prolonged fever (67%), chronic cough (54.4%), lymphadenopathy
      (52.4%), weight loss (50.5%), or chronic diarrhea (31%). The clinical
      manifestations included disseminated (17.4%) and localized (82.6%) infections.
      The localized infection included pulmonary infection (82.3%), followed by
      gastrointestinal infection (34.1%), skin infection (12.9%), lymphadenitis (8.2%),
      genitourinary tract infection (2.4%), central nervous system infection (2.4%),
      and keratitis (1.2%). Mycobacterium avium complex (MAC) was the predominant
      species (48.5%), followed by M. kansasii (19.4%), and rapidly growing
      mycobacteria (16.4%). Diffuse reticular infiltration was most commonly observed
      on chest radiography (53.4%). Abnormal laboratory findings included anemia
      (48.5%), hyponatremia (42.7%), and elevated alkaline phosphatase (39.8%). The
      overall mortality rate was 34.8% (45.9% and 11.1% in HIV- and HIV-noninfected
      patients). CONCLUSION: A diagnosis of NTM infection requires a high index of
      suspicion in patients especially with AIDS or immunocompromised status who
      present with prolonged fever, with or without organ-specific symptoms and signs.
      Therefore, clinical specimens must be sent for mycobacterial cultures for a
      definite diagnosis, a determination of the species of NTM, and an appropriate
      management. In addition to four standard antituberculous drugs, clarithromycin
      should be added for the treatment of MAC in patients with AIDS who presented with
      disseminated opportunistic infections before obtaining the microbiologic results.

PMID- 17214055
TI  - Relative fatigability of muscles in response to repetitive nerve stimulation in
      myasthenia gravis.
AB  - BACKGROUND: Repetitive nerve stimulation (RNS) plays an important role in the
      diagnosis of myasthenia gravis (MG). Technically, this test can be more easily
      performed on distal muscles than proximal muscles. On the other hand, proximal
      muscles have been shown to be more easily fatigued or more sensitive than the
      distal ones. OBJECTIVE: Evaluate the relative fatigability of different muscles
      in response to RNS in ocular and generalized MG patients. MATERIAL AND METHOD:
      Two hundred patients with 44 ocular MG and 156 generalized MG were studied The
      relative fatigability of each muscle was calculated as percentage of cases with
      abnormal response. A decrement of 10% or more of the amplitude of the compound
      muscle action potentials was considered abnormal. RESULT: The cases with abnormal
      response of adductor digiti minimi, anconeus, trapezius, nasalis and orbicularis
      oculi were 17%, 50%, 55%, 62%, 66% in ocular MG and 53%, 77%, 79%, 85%, 79% in
      generalized MG respectively. These results showed that in generalized MG the
      response in all the muscles was more frequently abnormal and was fatigable in a
      more comparable degree, whereas in ocular MG, the facial muscles were more often
      abnormal than the limb muscles. CONCLUSION: The abnormal response because of
      fatigability was more widespread in generalized MG whereas facial muscles were
      relatively more sensitive in ocular MG. This finding may be useful for the
      selection of the muscles to be tested in RNS especially in ocular MG.

PMID- 17214056
TI  - Efficacy of shoulder slings in shoulder subluxation of stroke patients.
AB  - OBJECTIVE: To assess the efficacy of the two types of shoulder slings in reducing
      shoulder subluxation in acute stroke patients. MATERIAL AND METHOD: Twenty-one
      acute stroke patients with shoulder subluxation were assessed for the subluxation
      distance before and after wearing the slings by physical examination and
      radiological measurement. The comparison by radiological measurement was
      performed by two radiologists who were blinded to each other as well as to the
      types of sling used. RESULTS: The mean difference of subluxation distance on the
      affected side after wearing the slings number 1 and 2 were 0.48 mm and 1.14 mm
      respectively on physical examination and 2.09 mm and 1.14 mm respectively on
      radiological assessment. There was no statistically significant difference of
      subluxation distance on either physical examination or radiological assessment (p
      > 0.05). CONCLUSION: There was no difference in efficacy of shoulder slings in
      reducing shoulder subluxation in acute stroke patients.

PMID- 17214058
TI  - Intensity-modulated radiation therapy in head-and-neck cancer, first report in
      Thailand.
AB  - OBJECTIVE: This is the first report in Thailand to evaluate the efficacy of using
      intensity-modulated radiotherapy (IMRT) in the primary treatment of head-and-neck
      cancer. MATERIAL AND METHOD: From July 2005 to March 2006, eighteen patients with
      head and neck cancer were treated with IMRT, fourteen of which were
      nasopharyngeal cancer. The median age at diagnosis was 52 years (range 23-58
      years). The treatment plan composed of two sequential plans for PTV-low risk
      (50Gy in 25 fractions) and PTV-high risk (20Gy in 10 fractions). Chemotherapy was
      given to 13 patients with locoregionally advanced disease (stage T3/T4 and N2/3)
      using cisplatin (n = 3) or carboplatin (n = 10) every 3 weeks during the course
      of radiation therapy. RESULTS: The median overall treatment time was 49 days
      (range, 43-57 days), and 77.8 percent of the patients completed 35 fractions
      within 50 days. The clinical complete response and partial response rates at 3
      months after complete radiation were 71.4% and 28.6%, respectively. However at
      the median follow-up of 5.6 months, the complete response rate increased to 89%.
      Treatment break during RT range from 3 to 7 days, was observed in three patients.
      All of them received concurrent chemoradiation. No distant metastasis was noted.
      CONCLUSION: The authors' experience of using concurrent chemotherapy with IMRT
      for a cohort of patients with head and neck carcinoma showed a very high rate
      response rate at early follow-up. Long-term clinical outcome is expected.

PMID- 17214057
TI  - Effect of Amifostine to prevent radiotherapy-induced acute and late toxicity in
      head and neck cancer patients who had normal or mild impaired salivary gland
      function.
AB  - BACKGROUND: Amifostine has a potential role for salivary gland protection in head
      and neck cancer patients who had radiotherapy. MATERIAL AND METHOD: Sixty-seven
      head and neck cancer patients were randomized to receive radiotherapy or
      radiotherapy plus Amifostine. The efficacy of the treatment was determined by a
      questionnaire evaluating dryness of mouth and the oral comfort, the RTOG/EORTC
      acute/late radiation morbidity scoring criteria, collection of the whole saliva
      and the 99mTc-pertecnetate scintigraphy of the salivary glands. RESULTS:
      Amifostine significantly reduced the mean questionnaire scores from 6.49 to 3.73,
      the incidence of grade > or = 2 mucositis from 75% to 36% and acute xerostomia
      from 82% to 39%. The salivary gland function returned to normal at a rate of
      36.3% in the Amifostine group versus 9.1% in the control group. CONCLUSION:
      Amifostine is effective in reducing the incidence and severity of acute
      mucositis, acute and late xerostomia in head and neck cancer patients.

PMID- 17214059
TI  - Botulinum toxin injection for treatment of spasmodic dysphonia: experience at
      Srinagarind Hospital.
AB  - BACKGROUND: Spasmodic dysphonia (SD) is a focal dystonia and adductor SD is the
      most common form. The standard treatment for adductor SD is EMG-guided,
      transcutaneous injections of botulinum toxin into the thyroarytenoid muscle.
      OBJECTIVE: Report the clinical presentation of SD, treatment with botulinum toxin
      injection, injection technique, results, and adverse effects. MATERIAL AND
      METHOD: A reviewed of clinical records of patients diagnosed with SD at the Voice
      Clinic between April 1999 and December 2004 at Srinagarind Hospital, Khon Kaen
      University, Thailand. Thirty-seven patients were identified but only twenty-five
      were treated with EMG-guided botulinum toxin injection to the thyroarytenoid
      muscle. RESULTS: In the presented 37 patients, SD was more common in women (89%)
      than men (11%). The median duration of symptoms prior to diagnosis was 12 months:
      all were the adductor type. The average age at onset was 46 years. The presenting
      symptoms included influence to the voice (84%), hoarseness (70%), strained or
      strangled voice (65%), decreased loudness (27%), and breathy voice (22%). A vocal
      tremor coexisted with dystonia in 60% of the presented patients. Treatment with
      botulinum toxin injection was carried out on 25 patients for 78 injections (mean,
      3 per patient). The time for botulinum toxin to take effect averaged 2.3 days
      (peak effect, 7 days). The patients received substantial relief from their SD
      symptoms, an average functional improvement of 39.2% (37.6% initially vs. 76.8%
      finally). Patients' best voice was achieved within one week and persisted for an
      average of 13.6 weeks. Side effects from the injections included mild breathiness
      (68%) and mild choking on fluid (56%). After injection, decreased potential for
      volume was a common complaint, but since all of the patients experienced
      increased fluency, they were satisfied. Almost all of the patients returned for
      repeat injections when the benefit diminished. CONCLUSION: Botulinum toxin
      therapy has become the standard care for the treatment of SD. An acceptable and
      flexible treatment plan to produce a balance between decreased spasms and loss of
      function must be developed for each patient.

PMID- 17214060
TI  - Sixty-one cases of obturator hernia in Chiangrai Regional Hospital: retrospective
      study.
AB  - OBJECTIVE: To review the patient characteristics and clinical symptoms,
      intraoperative finding and management, including morbidity and mortality rate of
      obturator hernia cases. MATERIAL AND METHOD: A retrospective study was performed
      in 61 patients diagnosed as obturator hernia at Chiangrai Regional Hospital
      between January 2000 and December 2005. RESULTS: The incidence of obturator
      hernia is 61 of 2,828 cases (2.2%) of all hernias, female:male 6.6:1. The mean
      age was 72.85 years. The mean body weight was 35.72 Kg. Howship-Romberg's sign
      were positive in eight patients (13.11%). Thirty-five patients (57.38%) were
      Richter type hernia, left:right side 3:2. Strangulation of bowel occurred in 41
      patients (67.21%) Mortality rate was 11.47%. All patients with postoperative
      complications and all deaths showed bowel strangulation and all were more than 70
      years of age. CONCLUSION: In the present study, the authors found a high
      incidence of obturator hernia (2.2% of all hernias) compared with a previous
      report (0.05%-1.4% of all hernias). This high incident rate might relate to the
      specific local life style of people in Chiangrai as most patients had a habit of
      smoking. Chronic obstructive pulmonary disease (COPD), old age, and low body
      weight were possible contributing factors. Bowel strangulation and age more than
      70 years old were associated with morbidity and mortality.

PMID- 17214061
TI  - Staghorn calculi in southern Thailand.
AB  - OBJECTIVE: To study the characteristics and components of staghorn calculi in
      southern Thailand. MATERIAL AND METHOD: 5,445 urolithiasis patients who underwent
      treatment in Songklanagarind Hospital between 1997 and 2000 were reviewed and 86
      of them were included by the criteria of "complete staghorn" calculi. General
      data, laboratory data at presentation, and the component analysis was performed
      with infrared spectroscopy were analyzed. RESULTS: Forty-three men and 43 women
      were included in the present study, with a mean age of 55.5 years for men and
      50.7 years for women. Uric acid was the most common component of staghorn calculi
      and 61.8% of the patients had hyperuricemia. Magnesium ammonium phosphate (MAP)
      was found in 11.6% of the calculi. A positive urine culture was found in 59.3% of
      the patients and the micro-organisms most frequently found were Corynebacterium
      sp and E. coli. CONCLUSION: There was a significant higher incidence of staghorn
      calculi in women in comparison with urolithiasis patients in southern Thailand,
      and the most common component was uric acid.

PMID- 17214062
TI  - Severe falciparum malaria in children at Somdejt Prachaotaksin Maharaj Hospital.
AB  - OBJECTIVE: Evaluate WHO guideline for the treatment of severe malaria. MATERIAL
      AND METHOD: A retrospective study in 41 pediatric patients who were admitted and
      diagnosed as severe malaria in Somdejtprachaotaksinmaharaj Hospital between July
      2003 and June 2006 was performed. RESULTS: Most patients were older than 5 years
      (83%). The common clinical features and complications were cerebral malaria
      (12%), severe anemia (7.3%), metabolic acidosis (7.3%), acute renal failure
      (4.8%) and pulmonary edema (4.8%). These were not different from other reports.
      Hypoglycemia and hemoglobinuria were not found. 58.5% of the children were
      classified as having increased risk of dying. All of them received intravenous
      artesunate and oral mefloquine with improvement. None of them died. Paracitic
      clearance time was about 2.6 days, fever clearance time was about 3.4 days and
      resistant type 1 was about 4%. CONCLUSION: Intravenous administration of
      antimalarial drug is essential for the group of children at increased risk of
      dying and artesunate plus mefloquine is effective.

PMID- 17214063
TI  - Environmental tobacco smoke exposure and respiratory syncytial virus infection in
      young children hospitalized with acute lower respiratory tract infection.
AB  - OBJECTIVE: The present study was performed to determine the relationship between
      environmental tobacco smoke (ETS) exposure and acute lower respiratory tract
      infection (LRI) caused by respiratory syncytial virus (RSV) in children. MATERIAL
      AND METHOD: The authors did the study in 71 children (median age 12 months; 60%
      male) who were admitted to King Chulalongkorn Memorial Hospital with acute LRI
      between June and September 2004. 27% had RSV infection. RESULTS: RSV-LRI required
      longer duration of oxygen therapy than non RSV-LRI (4.5 +/- 1.7 vs 2.8 +/- 1.3
      days; p < 0.001). Desaturation in room air was more common in the former group
      compared to the latter group (37 vs 11%; p = 0.01). There was no difference in
      urinary cotinine level between the two groups (median 0.5 vs 0.6 mcg/mg Cr; ns).
      Among RSV-LRI, those with desaturation had higher urinary cotinine level than
      those without desaturation (median 0.8 vs 0.0 mcg/mg Cr; p = 0.04). CONCLUSION:
      ETS exposure was not associated with RSV-LRI but increased the risk of
      desaturation in these patients.

PMID- 17214064
TI  - The self-reliant system for alternative care of diabetes mellitus patients-
      experience macrobiotic management in Trad Province.
AB  - BACKGROUND AND OBJECTIVE: Diabetes mellitus is a costly and growing health issue
      for the individual as well as the nation with much concern needed to change the
      way of life globally, Thailand included. Conventional medical care comprises of
      lifestyle modifications and the use of diabetic drugs but even with the
      development of new drugs, little achievement has been noted in relation to
      reducing the disease's complications. Macrobiotic is a holistic, alternative
      health care method. In macrobiotic principle, humans should live, drink and eat
      in conjunction with the laws of nature that will lead to good health, freedom and
      wisdom in understanding the laws of nature. The macrobiotic way of living is
      therefore the caring of body, mind, spirit and the environment in an independent
      manner based on adequacy and symbiotic support. MATERIAL AND METHOD: The present
      study consists of forty-four type 2 diabetes mellitus patients from the DM
      clinic, Trad Provincial Hospital. 4 subjects were insulin treated, observing the
      macrobiotic ways of living together at the Wanakaset Research Facility of
      Kasetsart University, Trad Province which lies in a natural forest area
      approximately 45 kilometers away from the city for a period of between 2 to 14
      weeks. The volunteers were required to refrain from using all kind of drugs or
      chemicals and eating Formula 2 food as set forth by the International Un Punto
      Macrobiotico Foundation, Italy while participating in all camp activities.
      RESULTS: The findings at the end of the program together with QOL assessment
      questionnaires noted a statistically significant reduction in blood sugar levels,
      weight, blood pressure and heart beat ratios. Subjects were in significantly
      better health, more vibrant, more peaceful, and more energetic. The 4 insulin
      treated volunteers managed to maintain their blood sugar level within the range
      of 110-171 mg% without any insulin injection and all volunteers are free of any
      adverse events. CONCLUSION: The results of the present study can be a guideline
      in the modification of health care policies that can lead to the development of
      effective, and alternative care of diabetes mellitus patients.

PMID- 17214065
TI  - The pharmacokinetics of pioglitazone in Thai healthy subjects.
AB  - BACKGROUND: Pioglitazone is a thiazolidinedione compound used in the treatment of
      type 2 diabetes, metabolized mainly by CYP2C8 and CYP3A4. Due to genetic
      polymorphisms in CYP2C8, interethnic variability in pharmacokinetics should be
      considered. OBJECTIVE: To conduct a study on the pharmacokinetics of pioglitazone
      in Thai subjects. MATERIAL AND METHOD: The present study was performed in 24 Thai
      male healthy subjects. After an overnight fasting, each subject had a single oral
      dose of 30 mg pioglitazone tablet. Serial blood samples were collected before and
      at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 9, 12, 24 and 48 hours after drug
      administration. Plasma pioglitazone was determined by automated High Performance
      Liquid Chromatography (HPLC) with UV detection after deproteinized with
      acetonitrile. The relevant pharmacokinetic parameters including peak plasma
      concentration (Cmax), time to peak plasma concentration (Tmax), elimination rate
      constant (Kel), elimination half-life (T1/2), area under the plasma concentration
      time curve (AUC(0-t), AUC(0-inf)), clearance (Cl) and volume of distribution (Vd)
      were determined. RESULTS: After a single oral dose of 30 mg pioglitazone tablet,
      the drug was absorbed into systemic circulation with time to maximum
      concentration (Tmax) at 2.00 +/- 1.61 (0.5-6) hr, and the plasma level reached
      the maximum concentration (Cmax) of 1.14 +/- 0.29 (0.47-1.63) microg/ml. The AUC
      was 11.47 +/- 4.77 and 16.69 +/- 7.75 microg x hr/ml for AUC(0-t) and AUC(0-inf)
      respectively. The elimination rate constant (Kel) of pioglitazone obtained was
      0.08 +/- 0.04 hr(-1), whereas the t1/2 was 11.19 +/- 7.38 hrs with the clearance
      (Cl) of 2.26 +/- 1.22 L/hr. The apparent volume of distribution (Vd) was found to
      be 30.19 +/- 13.06 L. CONCLUSION: Pharmacokinetic parameters of 30 mg single oral
      dose of pioglitazone were characterized in Thai subjects. These parameters showed
      that pioglitazone had a rapid rate of absorption, small volume of distribution
      and short elimination half-life.

PMID- 17214066
TI  - Appropriate cut-off level of BMI for screening in Thai adults.
AB  - OBJECTIVE: A cut-off level of Body Mass Index (BMI) for cardiovascular risk
      factors is controversial for its appropriateness in Asians. The present study
      aimed to determine the appropriate BMI cut-off level for Thai Adults. MATERIAL
      AND METHOD: 127 out of 387 teachers of at least 35 years of age from Phuket
      participated in the present study. Participants completed self-administered
      questionnaires, and had physical examination and blood drawn for lipid profile.
      RESULTS: In multivariate analysis, participants with BMI > or = 23 kg/m2 were 2.7
      (95% CI; 1.2, 61), 5.4 (2.3, 12.6), 5.1 (1.5, 16.0), and 7.2 (1.5, 34.1) times
      more likely to have total cholesterol > or = 240 mg/dl, high-density-lipoprotein
      < 40 mg/dl, low-density-lipoprotein > or = 160 mg/dl, and total cholesterol to
      HDL ratio > 5.0, respectively. CONCLUSIONS: For screening/education program, the
      BMI of 23 kg/m2 may be an appropriate cut-off level for being overweight. To
      support this finding, further studies in other regions and other populations of
      Thailand are needed.

PMID- 17214067
TI  - Inter- and intra-rater reliability of the Thai version of SCAN: Use of Alcohol
      and Use of Tobacco Section.
AB  - OBJECTIVE: To assess inter and intra rater reliability of the Thai version of Use
      of Alcohol and Use of Tobacco Section of the WHO Schedules for Clinical
      Assessment in Neuropsychiatry (SCAN). MATERIAL AND METHOD: Fifteen alcohol and/or
      tobacco dependence patients and fifteen controls with ages of > or = 18 years
      were recruited from October 2003 to August 2004 at Srinagarind Hospital. One
      psychiatrist interviewed and first rated under video-recording, then re-rated two
      weeks later. Another psychiatrist rated independently by looking at the
      videotapes for inter-rater reliability testing. RESULTS: The intra-rater kappa
      was 'excellent' for both sections. The inter-rater kappa for all items of
      "tobacco use" were 'excellent' (mean kappa = 0.84), and 'good' (mean kappa =
      0.66) for the "alcohol use". Items of dependence had 'good' kappa (mean kappa =
      0.73-0.95), except items of 'activities limitation (interest neglect)' and 'use
      despite knowledge of psychological/physical problems (continued use)' was 'fair'
      (mean kappa 062-0.49). The poor kappa (mean kappa = 0.17-0.38) was found in the
      item of 'physical and mental health problems due to drinking'. CONCLUSION: Thai
      SCAN provided reliable inter-rater diagnostic information for alcohol and tobacco
      dependence, but fair reliability for alcohol abuse. Improve understanding of the
      item concepts, better validity in questioning; giving examples of the focus
      symptoms, and frequent discussion about the respondent's answers, might improve
      overall validity and reliability.

PMID- 17214068
TI  - Acute epiglottitis: a report of the two different methods of airway management in
      adults.
AB  - The authors present two cases of acute epiglottitis with upper airway obstruction
      that urgently needed artificial airways. In case 1, a 55-year-old woman with DM
      presented with severe upper airway obstruction and sepsis. The tracheostomy was
      chosen for airway management, antibiotic was given, and fluid and inotropic drug
      (dopamine) were used for cardiovascular support. She received continuing care in
      the intensive care unit for several days. In case 2, a 40-year-old man presented
      with acute airway obstruction when he breathed forcefully. The prophylaxis
      tracheal intubation was done by using sevoflurane inhalation. The life
      threatening situations of both patients were managed successfully by the team
      approach of ENT surgeons, anesthesiologists, and intensivists.

PMID- 17214069
TI  - Paraplegia after thoracotomy for division and suture Patent Ductus Arteriosus
      (PDA).
AB  - A Thai women, aged 22 years old, came to hospital with Patent Ductus Arteriosis
      (PDA). Left thoracotomy, with division and suturing PDA, was performed. The
      second day after operation, she developed paraplegia below umbilical level. The
      CT-scan detected an extradural hematoma in the spinal cavity from T3-T6. To
      remove the blood clot, the T spine laminectomy was performed. 6 months after the
      laminectomy, the patient was able to perform her regular exercise.

PMID- 17214070
TI  - Methylprednisolone treatment in children with nephrotic primary focal segmental
      glomerulosclerosis.
AB  - OBJECTIVE: To examine the effectiveness of pulse methylprednisolone in children
      with nephrotic primary focal segmental glomerulosclerosis. MATERIAL AND METHOD:
      Medical records of children, who were treated with a pulse methylprednisolone
      regimen for nephrotic syndrome resulting from primary focal segmental
      glomerulosclerosis between 1987 and 2005, were retrospectively reviewed. The age,
      gender, urine protein, serum creatinine, and glomerular filtration rate at the
      onset of nephrotic syndrome were recorded. Urine protein, serum creatinine,
      glomerular filtration rate, and percentile of height before and after
      methylprednisolone treatment were compared. RESULTS: There were six patients (4
      male, 2 female) in the present report. The mean age at onset was 9.5 +/- 2.2
      years. Hypertension was noted in four patients and mild renal insufficiency in
      three. All patients had nephrotic-ranged proteinuria at onset and they were
      initially treated with prednisolone. Two were steroid-dependent and four were
      steroid-resistant. All of the steroid resistant cases were also resistant to oral
      cyclophosphamide. After methylprednisolone treatment, remission of proteinuria
      was noted in five patients (83%) (2 complete, 3 partial). Mean duration to
      remission was 20.8 weeks. There were no significant changes in serum creatinine
      (p = 0.43), GFR (p = 0.78) and percentile of height before and after treatment.
      No hypertension or cardiac arrhythmia was detected during methylprednisolone
      administration. The follow-up period after completion of the methylprednisolone
      regimen was 19.5 +/- 15.2 months (range 4-36 months). The clinical course of five
      patients with remission was characterized by sustained remission in three
      patients. Two patients relapsed at 2 and 8 months after treatment. CONCLUSION:
      Methylprednisolone was effective and safe in treating nephrotic children with
      primary focal segmental glomerulosclerosis. There was a high incidence of relapse
      shortly after the cessation of treatment. However, a larger number of patients
      and longer period of follow-up are needed to confirm this conclusion.

PMID- 17214071
TI  - Endoscopic removal of one live biliary Fasciola gigantica.
AB  - Biliary fascioliasis was diagnosed in a woman from Angthong province, who
      presented herself with anorexia, weight loss, and jaundice for one month.
      Intraoperative retrograded cholangiopancreatography revealed a filling defect
      considered as a stone and bile sludge. By the sphincterotomy and balloon
      extraction technique, one live fluke was removed and identified as Fasciola
      gigantica. A single dose of praziquantel, 25 mg/kg of body weight/day, was given
      although the postoperative stool examination revealed no Fasciola spp. egg. The
      patient was doing well after the fluke removal. According to a previous review,
      in this country, Ayutthaya is the southernmost province for the distribution of
      fascioliasis.

PMID- 17214072
TI  - Neuroleptic malignant syndrome: a review and report of six cases.
AB  - The typical symptoms and signs of neuroleptic malignant syndrome (NMS) consist of
      fever muscle rigidity (stiffness, myoclonus, rod-like), alterations of
      consciousness (confusion, agitation, aggression, or catatonia), autonomic nervous
      system disturbances (i.e., hypertension, tachycardia, tachypnea, profuse
      sweating, and urine incontinence), abnormal blood tests such as low serum
      electrolytes, elevated serum creatinine phosphokinase (CPK) level, and
      leukocytosis. Muscle rigidity is often associated with myonecrosis,
      myoglobinuria, and elevated serum CPK. The mortality among NMS cases is in the 10
      to 70% range depending on the severity of the symptoms and time of therapeutic
      approach. Mandatory therapy should include removal of causative agents,
      correction of body fluid and electrolytes, administration of benzodiazepine,
      clonazepam and bromocriptine (dopamine agonist), proved life-saving medications.
      The authors reported herein six cases with unusual clinical features of NMS. Four
      of them had been on antipsychotic for a year before becoming anorexic,
      dehydrated, agitated, and violent with paranoid delusion. One instance with
      underlying delirium tremens developed NMS after receiving haloperidol (30 mg IV)
      in addition to diazepam (200 mg IV) within 24 hours. Another patient was found to
      suffer from severe NMS after receiving bupropion (Dopamine inhibitor
      antidepressant) 300 mg/day. All patients displayed cardinal signs and symptoms of
      NMS in addition to dehydration and pallor. They were treated in the psychiatric
      ward and recovered rapidly from NMS after receiving clonazepam and bromocriptine
      and removal of the offending agents.

PMID- 17214073
TI  - Ethics of clinical pathologist.
AB  - Laboratory investigation is a general process in every hospital. Due to the
      increasing number of laboratory tests, physicians need to have a full awareness
      to prevent non ethical practice in laboratory process. Every physician should be
      aware of the medical ethics for clinical pathology. The cores medical ethics for
      clinical pathology include: 1. Proper laboratory request: Request only necessary
      tests with indication, not request aimed at service change from the patient and
      request all required tests without bias on the patients socioeconomic status. 2.
      Proper specimen collection procedure: "first, do no harm" to the patient,
      practice gently and bring the least suffering to the patient. 3. Proper keeping
      of laboratory result: Keep patients' information confidential, and do not change
      the laboratory results to increase the returns. Explanations and examples on some
      problems relating to the three topics are presented in Table 1 to help the reader
      realize the importance of these cores values.

PMID- 17214074
TI  - [The properties of Ebola virus proteins].
AB  - The paper describes the structure and functions of Ebola virus properties. It
      also presents information on the role of structural (NP, VP40, VP35, GP, VP30,
      VP24, and L) and secreted (sGP, delta-peptide, GP1, GP(1,2delta), ssGP) proteins
      in the viral replication cycle and in the pathogenesis of Ebola hemorrhagic
      fever.

PMID- 17214075
TI  - [Venezuelan equine encephalitis: state-of-the-art].
AB  - The paper provides the currently available data on the global prevalence of
      Venezuelan equine encephalitis (VEE), its epidemiology, clinical picture, and
      specific prevention in human beings. It also discussed the problem of potential
      use of the causative agent of VEE as a subject of bioterrorism.

PMID- 17214076
TI  - [Isolation of highly pathogenic avian influenza (HPAI) A/5H5N1 strains from wild
      birds in the epizootic outbreak on the Ubsu-Nur Lake (June 2006) and their
      incorporation to the Russian Federation State Collection of viruses (July 3,
      2006)].
AB  - Virological and molecular genetic studies of the field material collected in the
      epicenter of epizooty with high mortality rates among the wild birds on the coast
      of the Ubsu-Nur lake (Republic of Tyva, 51 degrees NL, 93 degrees EL, June 2006)
      revealed the etiological role of highly pathogenic avian influenza (HPAI) H5N1.
      Seven HPAI/H5N1 strains were isolated from the tracheal/cloacal swabs of
      clinically healthy, ill and recently dead great-crested grebes (Podiceps
      cristatus), cormorants (Phalacrocorax carbo), balt-coots (Fulica atra), and
      common terns (Sterna hirundo) collected on June 24, 2006, and incorporated to the
      RF State Collection of Viruses (with the July 3, 2006 priority). Full-length
      genome nucleotide sequences were incorporated to the GenBank (with the July 23,
      2006 priority) (DQ852600-DQ852607). Comparative analysis of molecular genetic
      characteristics showed their belonging to the Qinghai-Siberian genotype. The
      strains were sensitive to rimantadine.

PMID- 17214077
TI  - [Epidemiological characteristics of HIV infection in the Lipetsk Region in 1993
      2005].
AB  - The spread routes of HIV infection in the Lipetsk Region showing a low incidence
      of this infection rate are analyzed in detail. The findings indicate that the
      trend in identification of HIV-infected persons in this region reflects the all
      Russian HIV-infection spread situation, but the epidemic process has a number of
      features.

PMID- 17214078
TI  - [The molecular epidemiology of HIV-1 in Belarus in (1996-2004): a predominance of
      subtype A variants and circulation of subtype B variants].
AB  - To study the molecular epidemiology of HIV-1 in Belarus, the genetic sequences of
      HIV-1 variants were obtained from 50 infected persons, which represented the main
      stages, risk groups, and geographic areas of the epidemic. The env and gag
      sequences were studied for HIV-1 variants from 31 persons, the env sequences were
      for HIV-1 variants from 18 persons, and the gag sequence was for HIV-1 variant
      from 1 person. Phylogenetic analysis indicated that the sequences of HIV-1
      variants from 46 persons were homogenic and evolutionally closely related to IDU
      A strains specific for other epidemics in the former Soviet Union are dominating
      in the epidemic in Belarus. Circulation of epidemiologically unrelated subtype B
      viruses was also established.

PMID- 17214080
TI  - [Change in the antigenic structure of surface glycoprotein E of tick-borne
      encephalitis virus during its adaptation to ticks and mammals].
AB  - Enzyme immunoassay and immunoprecipitation test of viral proteins, by applying a
      tick-borne encephalitis (TBE) viral protein E monoclonal antibody kit, have shown
      that TBE adaptation to ticks and mammals may cause a considerable change in the
      antigenic structure of surface glycoprotein E, by involving different antigenic
      domains, including a neutralizing epitope that seems to participate at the early
      stages of interaction of virions with the cell membrane.

PMID- 17214079
TI  - [The properties of the epidemic influenza viruses A and B strains circulating in
      Russia in the 2004-2005 epidemic season].
AB  - The epidemic upsurge of influenza morbidity in Russia in 2004-2005 was caused by
      the active circulation of influenza A(H3N2) and B viruses. A hundred and sixty
      six epidemic strains were studied. All the strains were isolated in the MCK cell
      culture. Influenza A(H3N2) viruses (n=77) were antigenic variants of the
      reference A/Fujian/411/ 2002 and A/California/7/2004 strains. Three influenza
      A(H1N1) viral strains that were antigenic variants of A/New Caledonia/20/99
      strains were isolated in sporadic cases. Influenza B virus strains (n=83) were
      antigenic variants of the reference B/Shanghai/361/02--lineage B/Yamagata/l6/88.
      In addition, 3 antigenic variants of B/Hong Kong/ 330/2002 (lineage
      B/Victoria/2/87) strains were isolated. Nine (20%) strains resistant to
      rimantadine at a concentration of 5 microg/ml were identified. Chromatographic
      analysis of B/Shanghai/361/02 and BIHong Kong/330/01 viral protein M1 trypsin
      hydrolysates revealed differences in the profiles of chromatograms of influenza A
      virus proteins M1. Examination of 121 pair sera from patients revealed an
      increase in antibodies to influenza A(H3N2) viruses in 10-21% of cases and to
      influenza B viruses in 20-36% of cases.

PMID- 17214081
TI  - [Immunopathogenetic features of tick-borne encephalitis under long-term viral
      antigenemia].
AB  - The occurrence of chronic tick-borne encephalitis viral antigenemia characterized
      by the asymptomatic course or minimal clinical manifestations is caused by the
      virus-immune cell interaction. Cellular immunity was studied in 183 patients with
      chronic (more than 6-month) tick-borne encephalitis viral antigenemia, by
      evaluating the immunophenotypic and cytogenetic statuses, structural and
      functional features, cytokine profile, and peripheral lymphocytic apoptosis. The
      findings suggest impairments in the cooperation of immunocompetent cells and in
      the classical scheme of antiviral immunity regulation in tick-borne encephalitis
      viral persistence due to the changes in lymphocytic structural and functional
      properties.

PMID- 17214082
TI  - [Preclinical studies of the anticancer adenovirus cancerolysin preparation].
AB  - The anticancer drug Cancerolysin has been developed, by using the mutant Adel2
      variant of human adenovirus serotype 5 designed at the State Research Center of
      Virology and Biotechnology. Cancerolysin possesses a high degree of replication
      activity for complementary cells 293 and p53-deficient tumor cells and, at the
      same time, has significant replication limitations in normal human cells.
      Preclinical studies of the drug on laboratory animals (mice, rabbits, guinea
      pigs) have demonstrated its harmlessness and safety. When stored at -40 and -70
      degrees C, the drug showed no significant activity throughout the control
      observational period (1 year).

PMID- 17214083
TI  - [Global eradication of poliomyelitis: intralaboratory contamination with wild
      poliovirus in the implementation of the program for safe laboratory containment
      of wild-type polioviruses in the Russian Federation].
AB  - The paper describes a case of contamination of sewage samples by a wild
      poliovirus type 1 strain (Mahoney) in one of the virological laboratories of the
      Russian Federation. It discusses the possible sources and the mechanism of
      contamination, as well as the problems in the implementation of the program for
      safe laboratory containments of wild-type polioviruses.

PMID- 17214085
TI  - Risk factors for ischemic stroke: electrocardiographic findings.
AB  - BACKGROUND: Standard 12-lead electrocardiography is a routine and mandatory
      cardiovascular examination in the evaluation of stroke patients. This study
      investigates the relationship of electrocardiography findings and first-ever
      ischemic stroke. METHODS: This hospital-based case-control study consisted of 238
      consecutively hospitalized cases of first-ever ischemic stroke and 238 healthy
      age- and sex-matched control subjects. Multivariate logistic regression analyses
      were performed to evaluate the risk factors and electrocardiography findings.
      RESULTS: Atrial fibrillation [odds ratio (OR) = 6.8, 95% confidence interval (CI)
      =1.90-24.45], myocardial ischemic change (OR = 5.0, 95% CI = 2.22-11.06), left
      ventricular hypertrophy (OR = 3.9, 95% CI = 2.02-7.39) and sinus bradycardia (OR
      = 0.37, 95% CI = 0.18-0.79) were significantly related with first-ever ischemic
      stroke. CONCLUSIONS: Electrocardiography findings of atrial fibrillation,
      myocardial ischemic change and left ventricular hypertrophy as risk factors for
      ischemic stroke were similar to those from other studies. Additional studies are
      needed to assess the role of sinus bradycardia for ischemic stroke, which was
      less common in patients with stroke than in controls.

PMID- 17214084
TI  - New routes for delivery of anti-epileptic medications.
AB  - Use of novel drug delivery methods might enhance efficacy and reduce toxicity, in
      comparison with currently existing oral anti-epileptic drugs (AEDs). Novel
      methods aim to deliver optimal drug concentration more specifically to the
      seizure focus or foci. In this review, we first consider unconventional routes of
      drug delivery to the peripheral system, then potential new methods of targeted
      CNS drug delivery. Intrathecal or intraventricular AEDs might circumvent systemic
      toxicity. Drug-eluting wafers could be surgically positioned over an
      epileptogenic region of brain. Drug can be delivered to a seizure focus by an
      implanted catheter and subcutaneous pump. Inactive prodrugs, given systemically,
      can be made active only at the seizure focus, by interaction with locally
      released substances. Liposomes and polysomes are engineered slow-release storage
      vehicles for drugs. Targeting components can hold liposomes near a region of
      interest, provided that they can penetrate the blood brain barrier. Lastly, we
      discuss future prospects for the use of transplanted cells and genes as potential
      vehicles for local delivery of renewable anti-epileptic regimen.

PMID- 17214086
TI  - Risk factors of carotid stenosis in first-ever ischemic stroke in Taiwan: a
      hospital-based study.
AB  - OBJECTIVE: The aim of this study is to identify the risk factors of extracranial
      carotid atherosclerosis in patients with first-ever ischemic stroke. MATERIAL AND
      METHODS: A total of 541 consecutive first-ever ischemic stroke patients were
      enrolled in the present study. We examined clinical and laboratory factors that
      were potentially relevant to extracranial carotid artery atherosclerosis. The
      degree of carotid stenosis was diagnosed based on B-mode ultrasonography.
      RESULTS: The sample contained 325 men and 216 women. Among these patients, 80%
      had a < 50% carotid stenosis and 20% had a > or = 50% carotid stenosis. Multiple
      logistic regression analysis revealed that age (odds ratio = 2.15, 95% CI = 1.06
      1.11, P < 0.001) and smoking (odds ratio = 1.52, 95% CI = 1.17-3.54, P = 0.012)
      were significantly associated with > or = 50% carotid stenosis. CONCLUSIONS: In
      the present study, age and smoking are found to be the independent risk factors
      for carotid atherosclerosis. The identification of these risk factors may improve
      our knowledge in the primary prevention of ischemic stroke in Taiwan.

PMID- 17214087
TI  - Vigabatrin-attributable visual field defects in patients with intractable partial
      epilepsy.
AB  - INTRODUCTION: Vigabatrin (VGB) is implicated to cause visual field defects. We
      estimated the prevalence, described the characteristics and investigated the risk
      factors of VGB-attributable visual field defects. METHODS: Patients with
      intractable partial epilepsy under VGB add-on treatment received static
      perimetric examinations. Visual field charts were reviewed and interpreted using
      a three-grade system. Clinical features and therapeutic courses were analyzed for
      possible risk factors. RESULTS: Visual field defects in at least one eye were
      detected in 27 (79%) of 34 patients. In the subgroup of 27 patients with both
      eyes reliably tested, 16 (59%) had bilateral defect, among whom seven were
      severely involved and showed nasally dominant, crescent or concentric defect.
      Five patients had unilateral visual field defects. Four out of the 27 affected
      patients reported blurred vision. No statistically significant differences were
      noted between patients with and without visual field defects in terms of gender,
      age, duration or etiology of the epilepsy, and duration, maximum daily dose, or
      cumulative dose of VGB. CONCLUSIONS: There was a high prevalence of VGB
      attributable visual field defects. No risk factors could be identified. Routine
      initial and regular follow-up of visual field examination, especially that
      focusing within a range of central fixation to 60 degrees, should be performed in
      patients on VGB.

PMID- 17214088
TI  - Scrub typhus-associated acute disseminated encephalomyelitis.
AB  - BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a monophasic
      demyelinating disease of the central nervous system, typically occurring after
      infections or vaccinations. To our knowledge, scrub typhus has not been described
      in association with ADEM. CASE REPORT: A 77-year-old man was admitted with fever,
      convulsions and an altered level of consciousness. On neurological examination,
      the patient was stuporous and had nuchal rigidity and left hemiparesis. A
      generalized tonic-clonic seizure was observed. Serum and cerebrospinal fluid
      samples were positive for anti-Orientia tsutsugamushi antibody. Despite a 10-day
      course of parenteral minocycline, his clinical condition deteriorated. Serial
      cranial magnetic resonance images demonstrated progressively extensive areas of
      signal hyperintensity on conventional T2-weighted and fluid attenuated inversion
      recovery sequence images, mainly affecting the periventricular white matter.
      After administration of intravenous high-dose corticosteroids, the patient had
      limited improvement. CONCLUSIONS: This is the first identifiable case of ADEM
      temporally associated with scrub typhus alone.

PMID- 17214089
TI  - Skull base osteomyelitis presenting as Villaret's syndrome.
AB  - This report documents a 47-year-old male who developed acute deficits of the IX,
      X, XI, XII cranial nerves and Horner's symptoms, consistent with Villaret's
      syndrome. Neuroimaging studies demonstrated an osteolytic lesion in the skull
      base involving the clivus and jugular foramen. The patient recovered after the
      antibiotic treatment for proteus mirabilis infection. We suggest that Villaret's
      syndrome can be a rare presentation of skull base osteomyelitis.

PMID- 17214090
TI  - Exercise test in the inter-attack period of thyrotoxic periodic paralysis: a
      useful diagnostic tool.
AB  - Exercise test was reported to be useful for some patients with periodic
      paralysis. We report here the results of exercise test in three cases of
      thyrotoxic periodic paralysis, for whom the exercise test was all positive.
      Exercise test could be one of the diagnostic tools in the "inter-attack" state of
      the probable cases with thyrotoxic periodic paralysis. However, the case number
      of this study is small and larger-scale studies may be warranted in the future.

PMID- 17214091
TI  - Intravascular lymphomatosis mimicks a cerebral demyelinating disorder.
AB  - Intravascular lymphomatosis is a rare extra-nodal form of diffuse, large B-cell
      non-Hodgkin's lymphoma that causes a myriad of neurological symptoms, including
      focal neurological deficits, cognitive decline, and seizure. Intravascular
      lymphomatosis is difficult to make ante-mortem diagnosis because of its variable
      clinical presentation and non-specific laboratory findings. Neuroimaging findings
      also vary widely in patients of intravascular lymphomatosis. We present, herein,
      a patient with rapidly deteriorating neurological deficit whose brain MRI
      revealed rapidly progressing white matter diseases. This patient was diagnosed
      and treated as having a cerebral demyelinating disorder. Intravascular
      lymphomatosis involving multiple organs was finally diagnosed after autopsy.

PMID- 17214092
TI  - Acute neurological deficits caused by cefipime: a case report and review of
      literature.
AB  - Cefepime (Maxipime) is a fourth-generation cephalosporin commonly used to treat a
      variety of infections. Its controversial side effect profile is not well
      appreciated by first-line practitioners. We report a case of urinary tract
      infection treated with cefepime in a 91-year-old woman. The acute onset of
      conscuous disturbance was noted on the 9th day of cefepime treatment. Computed
      tomogram and magnetic resonance image of the brain showed no specific findings.
      The neurological symptoms and signs such us conscious disturbance, ocular
      bobbing, asterexis disappeared after discontinuation of cefepime. We suggest that
      physicians should cefepime as a possible cause of reversible neurological
      deficits.

PMID- 17214093
TI  - [Hormone replacement therapy and cognitive function].
AB  - Observational studies have suggested that postmenopausal hormone replacement
      therapy (HRT) may improve cognitive function, but data from randomized clinical
      trials have been sparse and inconclusive. The effects of HRT on dementia and mild
      cognitive impairment were assessed in a subgroup of participants in the Women's
      Health Initiative Memory Study (WHIMS) (a multicenter, randomized, double-blind,
      placebo-controlled clinical trial). There were two study arms, one involved 4,532
      postmenopausal women who received continuous combined estrogen (conjugated equine
      estrogens [CEE] plus medroxyprogesterone acetate [MPA]) or placebo, and the other
      involved 2,947 hysterectomized women randomized to continuous unopposed CEE or
      placebo. All participants were aged 65 years or older. CEE with or without MPA
      did not protect against (but substantially increased the risk of) dementia of any
      cause or cognitive decline. Incidence of probable dementia in the estrogen-alone
      trial was statistically similar to that in the estrogen plus progestin trial.
      When data from both trials were pooled, the overall risk for probable dementia
      was increased by 76% (HR, 1.76; 95% CI, 1.19 to 2.60; P = 0.005). A second report
      from WHIMS suggested that cognitive decline in women aged 65 years and older was
      greater in those receiving hormone therapy than in those receiving placebo (HR,
      1.25; 95% CI, 0.97-1.60). The WHIMS results clearly indicate that CEE with or
      without MPA should not be used to prevent dementia or enhance cognition in women
      older than 65 years.

PMID- 17214094
TI  - Abnormal brain MR signal intensity in a patient with toluene abuse.

PMID- 17214095
TI  - Clinical and immunologic aspects of B chronic lymphocytic leukemia associated
      with autoimmune disorders.
AB  - BACKGROUND: Autoimmune disorders often develop during the course of B chronic
      lymphocytic leukemia. The source of the autoantibodies is still uncertain: either
      uncontrolled production of the malignant B cells or disturbances of the residual
      normal B and T cells involved in the immune system. OBJECTIVES: To evaluate
      immunologic parameters in B-CLL associated with autoimmune disorders. As a
      hypothesis we postulated that in those cases, the malignant B cells might
      disclose an activated phenotype pattern leading to the production of
      autoantibodies. METHODS: In the Registry of the Israel Study Group on CLL that
      includes 964 patients, we found 115 cases showing a single or a complex of
      autoimmune disorders. We evaluated the lymphocyte morphology, immunoglobulin G
      and beta-2-microglobulin serum levels and positivity of the CD38 and FMC7
      markers, and compared these values with those of a matched CLL population without
      autoimmune disorder. RESULTS: The main autoimmune disorders encountered were
      autoimmune hemolytic anemia (55 patients), Evan's syndrome (n=7), Hashimoto's
      thyroiditis (n=15), vasculitis (n=5) and rheumatoid arthritis (n=4). We found
      atypical prolymphocytic morphology in 22%, high expression of the activation
      antigens CD38 and/or FMC7 in 30%, and high level of immunoglobulin G (> 1000
      mg/dl) and beta-2-microglobulin in 57% and 78% respectively. When compared with a
      matched CLL population without an autoimmune disorder, these values were
      statistically significant. CONCLUSIONS: Our data, which show activated lymphocyte
      morphology, high levels of IgG and beta-2-microglobulin, and increased expression
      of CD38 and/or FMC7 in a significant number of cases, suggest that some degree of
      activation of B cells may lead to the occurrence of an autoimmune disorder in
      CLL.

PMID- 17214096
TI  - Non-Hodgkin's lymphomas of the colon.
AB  - BACKGROUND: Non-Hodgkin's lymphoma of the colon is a rare and consequently poorly
      studied extranodal lymphoma. Most of the previous publications used old
      pathologic classifications and old diagnostic and treatment approaches.
      OBJECTIVE: To examine the clinical presentation, pathologic classification,
      treatment and outcome of patients with NHL of the colon. METHODS: A retrospective
      study was performed of all patients with NHL and involvement of the colon in two
      medical centers. The patient group consisted of 17 patients over a 13 year
      period. RESULTS: Fourteen patients had primary involvement and 3 secondary. The
      ileocecal region and cecum were the most frequent sites of involvement, occurring
      in 76% of patients. Most patients had bulky disease: three had a diameter >5 cm
      and eight a diameter >10 cm. Aggressive histology was found in 12 patients:
      diffuse large B cell lymphoma in 11 and peripheral T cell lymphoma in 1. Three
      patients had mantle cell lymphoma and two had indolent lymphomas: mucosa
      associated lymphoid tissue (n=l) and small lymphocytic (n=l). Eleven patients
      underwent hemicolectomy: right sided in 9 and left sided in 2, and 5 DLBCL
      patients required emergency surgery for intestinal perforation. The median
      overall survival was 44 months (range 1-147). Disease stage influenced prognosis;
      six of seven patients with limited-stage DLBCL who received aggressive
      chemotherapy achieved complete remission and enjoyed prolonged survival, whereas
      patients with aggressive disseminated disease had resistant disease and poor
      survival (median 8 months). CONCLUSIONS: Most colonic lymphomas are aggressive B
      cell lymphomas. Diagnosis is often delayed. Early diagnosis may prevent
      perforation. Those with limited-stage disease when treated with aggressive
      chemotherapy may enjoy prolonged survival. The role of elective hemicolectomy to
      prevent perforation should be examined in prospective trials.

PMID- 17214097
TI  - A clonal hypereosinophilic syndrome with specific and effective therapy: a report
      of two cases.

PMID- 17214098
TI  - 18F-fluorodeoxyglucose-Avid mammary mass in a patient with insulin-dependent
      diabetes mellitus and Hodgkin's lymphoma: relapse or pitfall?

PMID- 17214099
TI  - Should bone marrow examination be routinely performed for the diagnosis of
      monoclonal gammopathy of undetermined significance?
AB  - BACKGROUND: Monoclonal gammopathy of undetermined significance is defined by the
      presence of: low serum and/or urine monoclonal protein level; less than 10%
      plasma cells in bone marrow; normal serum calcium, creatinine and
      hemoglobinlevels; and no bone lesions on full skeletal X-ray survey. OBJECTIVES:
      To study the necessity of bone marrow examination for the diagnosis and clinical
      course of MGUS. METHODS: We retrospectively screened the medical records of all
      patients in whom monoclonal protein was found in the serum during 2001-2002 in
      the medical laboratories of Meir Medical Center. Asymptomatic patients who had
      serum monoclonal immunoglobulin G < 3.0 g/dl or IgA < 2.0 g/dl or IgM < 1.0 g/dl
      without anemia, renal failure, hypercalcemia or any bone lesions on skeletal
      survey were eligible. Full records of patients who were evaluated in the
      hematology clinic were available (group 1). The remaining patients were followed
      by their family physicians; thus we had access only to their electronic files
      including laboratory results and new diagnoses (group 2). Demographic and
      clinical parameters as well as clinical course werewere evaluated. RESULTS: Both
      groups (57 and 255 patients, respectively) had similar demographic, laboratory
      and clinical characteristics. Bone marrow examination was performed in 30 of 57
      patients (group 1): 16 were normal, 8 had an excess of normal plasma cells, and 6
      had excess of pathologic plasma cells. However, only in two of the latter six
      could a diagnosis of multiple myeloma be established. All group 1 patients were
      followed for 22 +/- 11 months and onlytwo developed overt multiple myeloma.
      During the same period, 6 of 255 patients (group 2) were diagnosed as multiple
      myeloma and 3 as MGUS in other hospitals. The rest had a stable course with no
      change in their laboratory values. CONCLUSIONS: Our findings suggest that bone
      marrow examination should not be performed routinely in patients who fulfill
      strict clinical and laboratory criteria of MGUS.

PMID- 17214100
TI  - Targeted and tailored therapy in hemato-oncology: vision for the 21st century.
AB  - Summarizing our vision of hemato-oncology in the 21st century, we believe that
      with time, and with the expected progress in both medicine and biotechnology, the
      role of non-specific chemotherapy will decrease, while that of targeted therapies
      will increase. Unfortunately, for most tumors chemotherapy is still the
      cornerstone of treatment. We should therefore focus on finding more targeted
      agents, better tailoring of treatments, and identifying the risk factors for
      cancer development and the means of prevention of--what is likely to be--the
      number one killer of this century.

PMID- 17214101
TI  - Evaluation of arterial compliance in polycythemia vera patients: short and long
      term influence of phlebotomy.
AB  - BACKGROUND: Thrombosis is a major cause of morbidity and mortality in
      polycythemia vera. Hypercoagulability is principally due to hyperviscosity of the
      whole blood, an exponential function of the hematocrit. PV is also associated
      with endothelial dysfunction that can predispose to arterial disease. Reduction
      of the red cell mass to a safe level by phlebotomy is the first principle of
      therapy in PV. This therapy may have some effect on the arterial compliance in PV
      patients. OBJECTIVES: To estimate the influence of phlebotomies on large artery
      (Cl) and small artery compliance (C2) in PV patients by using non-invasive
      methods. METHODS: Short-term hemodynamic effects of phlebotomy were studied by
      pulse wave analysis using the HDI-Pulse Wave CR2000 (Minneapolis, MN, USA) before
      and immediately after venesection (350-500 ml of blood). We repeated the
      evaluation after 1 month to measure the long-term effects. RESULTS: Seventeen PV
      patients were included in the study and 47 measurements of arterial compliance
      were performed: 37 for short-term effects and 10 for long-term effects. The mean
      large artery compliance (C1) before phlebotomy was 12.0 ml/mmHg x 10 (range 4.5
      28.6), and 12.6 ml/mmHg x 10 (range 5.2-20.1) immediately after phlebotomy (NS).
      The mean small artery compliance (C2) before and immediately after phlebotomy
      were 4.4 mg/mmHg x 10 (range 1.2-14.3) and 5.5 mg/mmHg x 10 (range 1.2-15.6)
      respectively (delta C2-1.1, P < 0.001). No difference in these parameters could
      be demonstrated in the long-term arm. CONCLUSIONS: Phlebotomy immediately
      improves arterial compliance in small vessels of PV patients, but this effect is
      short lived.

PMID- 17214102
TI  - Prospective evaluation of patients hospitalized with venous thromboembolism:
      comparison between cancer and non-cancer patients.
AB  - BACKGROUND: Little is known about the epidemiology of venous thromboembolism in
      hospitalized patients in Israel. Also, a direct comparison of the clinical and
      laboratory features between cancer and non-cancer patients has not yet been
      reported. OBJECTIVES: To investigate and compare the epidemiologic, clinical and
      laboratory characteristics of cancer and non-cancer patients hospitalized with
      venous thromboembolism in a large referral medical center in Israel. METHODS:
      Between February 2002 and February 2003, patients diagnosed at the Rambam Medical
      Center as suffering from VTE (deep vein thrombosis and/or pulmonary embolism),
      based on diagnostic findings on Doppler ultrasonography, spiral computed
      tomography scan or lung scan showing high probability for pulmonary embolism,
      were prospectively identified and evaluated. In addition, at the conclusion of
      the study period, the reports of spiral chest CT scans, performed during the
      aforementioned period in this hospital, were retrospectively reviewed to minimize
      the number of unidentified cases. Blood samples were drawn for evaluation of the
      coagulation profile. RESULTS: Altogether, 147 patients were identified and 153
      VTE events diagnosed, accounting for 0.25% of all hospitalizations during the
      study period. The cancer group included 63 patients (43%), most of whom had
      advanced disease (63%). The most common malignancies were cancer of the lung
      (16%), breast (14%), colon (11%) and pancreas (10%). Of 122 DVT events (with or
      without pulmonary embolism) there were 14 upper extremity thromboses (12%). The
      most common risk factors for VTE, except malignancy, were immobilization (33%),
      surgery/trauma (20%) and congestive heart failure (17%). There was no difference
      in prevalence of various risk factors between cancer and non-cancer patients.
      During an acute VTE event, D-dimer levels were higher in cancer patients than non
      cancer patients (4.27 +/- 4.04 vs. 2.58 +/- 1.83 mg/L respectively, P = 0.055).
      Relatively low values of activated protein C sensitivity ratio and normalized
      protein C activation time were observed in both cancer and non-cancer groups
      (2.05 +/- 0.23 vs. 2.01 +/- 0.33 and 0.75 +/- 0.17 vs. 0.71 +/- 0.22,
      respectively). These values did not differ significantly between the groups.
      CONCLUSION: The proportion of cancer patients among patients suffering from VTE
      was high. Their demographic, clinical and laboratory characteristics (during an
      acute event) were not different from those of non-cancer patients, except for
      higher D-dimer levels.

PMID- 17214103
TI  - Disseminated intravascular coagulation at presentation of advanced gastric
      cancer.
AB  - BACKGROUND: Disseminated intravascular coagulation associated with malignant bone
      marrow involvement has been described as a rare complication of gastric carcinoma
      and most patients die within 1-4 weeks. Effective chemotherapy of the underlying
      malignancy may be the only way to control acute DIC. OBJECTIVES: To assess the
      benefit of infusional 5-fluorouracil as the primary treatment of metastatic
      gastric carcinoma and DIC at diagnosis. METHODS: From February 2001 to January
      2005, six women (median age 48 years) with gastric carcinoma who presented with
      diffuse bone metastases and acute DIC were treated in our department. Diagnosis
      was based on primary gastric and bone marrow biopsies. DIC was confirmed by
      laboratory findings. Initial treatment consisted of infusional 5FU 200 mg/m2/day.
      When the bleeding tendency stopped, cisplatin 60 mg/m2 and epirubicin 50 mg/m2
      every 3 weeks were added. RESULTS: Within one week of starting the treatment, the
      clinical and laboratory signs of acute DIC were resolved in five of six patients.
      Upon clinical improvement, five patients subsequently received epirubicin and
      cisplatin. Survival, however, was short (mean 15 weeks). All patients died with
      symptoms of bleeding, showing clinical and laboratory signs of DIC. CONCLUSIONS:
      Based on our experience, infusional 5FU is an effective regimen with negligible
      myelosuppression; thus, it may be a good choice as initial therapy for this group
      of patients. The response induced by protracted 5FU was usually short and lasted
      for only a few weeks. Therefore, once DIC symptoms are controlled, the addition
      of newer cytotoxic drugs may be necessary to consolidate the remission.

PMID- 17214104
TI  - Catastrophic antiphospholipid syndrome in the second trimester of pregnancy.

PMID- 17214105
TI  - Mesenterial thrombosis with the antiphospholipid syndrome.

PMID- 17214106
TI  - Routine chemoprophylaxis for travel-associated thrombosis? No.

PMID- 17214107
TI  - Autoimmunity in chronic lymphocytic leukemia: which B lymphocyte is the culprit?

PMID- 17214108
TI  - The use of medical informatics as a management tool for community health services
      during the 2006 Israel-Lebanon War.
AB  - BACKGROUND: During war the health management organizations have tremendous
      difficulty monitoring members' needs according to geographic spread. OBJECTIVES:
      To describe how an HMO used its health information technology in a way that
      enables its management to receive updated online information on the needs of the
      insured, according to their distribution throughout the country during the time
      of the war in Lebanon in July-August 2006. METHODS: Data were derived from the
      computerized medical records of Maccabi Healthcare Services--the second largest
      HMO in Israel, providing care to more than 1.7 million members nationwide. Data
      on healthcare utilization by northern members were compared to the geographic
      distribution of clinics. RESULTS: The war was characterized by the massive
      evacuation of citizens southwards. During this period there was an abrupt decline
      in the utilization of medical services by northern members in the northern
      region. This decline returned to normal 10 days after the ceasefire. A reciprocal
      increase was noted in the use of health services by citizens from the north in
      other regions. This increase returned to normal after the war. No such pattern
      was noticed during the same period in 2005. CONCLUSIONS: Real-time surveillance
      of trends in consumption of health services by citizens in times of regular daily
      living as well as during emergencies and wars is a vital management tool for
      medical directors responsible for providing health services.

PMID- 17214109
TI  - Tube feeding in the demented elderly with severe disabilities.
AB  - BACKGROUND: Despite the ongoing debate on tube feeding of severely demented
      patients, the current approach in western countries is to avoid feeding by tube.
      OBJECTIVES: To assess the clinical course and outcome of demented elderly
      patients with severe disabilities, by feeding mode. METHODS: The study was
      conducted in a skilled nursing department of a major psychogeriatric hospital in
      Israel. Eighty-eight patients aged 79 +/- 9 years were followed for 17 months: 62
      were fed by nasogastric tube and 26 were orally fed. The groups were compared for
      background characteristics, underlying medical condition, functional impairment,
      clinical and nutritional outcomes, and survival. RESULTS: Tube feeding had no
      beneficial effect on clinical and nutritional outcomes or on healing preexisting
      pressure ulcers, compared with oral feeding. Very few patients on tube feeding
      showed signs of discomfort, partly because of low cognitive function. Survival
      was significantly higher in the tube-fed patients (P < 0.001), which could be
      partly explain by the different case mix (i.e., the underlying diseases)
      CONCLUSIONS: Tube feeding seems to have no nutritional advantage in severely
      demented elderly patients. Median survival was longer in tube-fed individuals who
      had no acute co-morbidity. However, since tube feeding does not add to patient
      pain and discomfort, it should not be contraindicated when it complies with the
      values and wishes of patients and their families.

PMID- 17214110
TI  - Adherence to guidelines for patients hospitalized with heart failure: a
      nationwide survey.
AB  - BACKGROUND: Despite significant advances in the therapy of heart failure, many
      patients still do not receive optimal treatment. OBJECTIVES: To document the
      standard of care that patients hospitalized with HF in Israel received during a 2
      month period. METHODS: The Heart Failure Survey in Israel 2003 was a prospective
      2 month survey of patients admitted to all 25 public hospitals in Israel with a
      diagnosis of HF. RESULTS: The mean age of the 4102 patients was 73 years and 43%
      were female. The use of angiotensin-converting enzyme/angiotensin receptor
      blockers and beta blockers both declined from NYHA class I to IV (68.8% to 50.6%
      for ACE-inhibitor/ARB and 64.1% to 52.9% for beta blockers, P < 0.001 for
      comparisons). The percentage of patients by NYHA class taking an ACE-inhibitor or
      ARB and a beta blocker at hospital discharge also declined from NYHA class I to
      IV (47.5% to 28.8%, P < 0.002 for comparisons). The strongest predictor of being
      discharged with an ACE-inhibitor or ARB was the use of these medications at
      hospital admission. Negative predictors for their usage were age, creatinine,
      disease severity class, and functional status. CONCLUSIONS: Despite the
      dissemination of guidelines many patients did not receive optimal care for HF.
      Reasons for this discrepancy need to be identified and modified.

PMID- 17214111
TI  - Estimation of prevalence and incidence rates and causes of blindness in Israel,
      1998-2003.
AB  - BACKGROUND: The prevalence and incidence of blindness in Israel appear to be
      comparable to other western countries. Comparisons are difficult because of
      different definitions of blindness, and the uniqueness of the Israeli Registry of
      the Blind. OBJECTIVE: To characterize the population who were registered as Blind
      in Israel in the years 1998-2003 and estimate the prevalence and incidence of
      blindness by age and causes of blindness. METHODS: A retrospective review of the
      annual report of the national Registry of the Blind in Israel between 1998 and
      2003 identified 21,585 blind persons who received a certificate for blindness.
      Blind persons are identified by ophthalmologists throughout Israel and referred
      to the Registry of the Blind if they have a visual acuity of 3/60 or worse, or a
      visual field loss of <20 degrees in their better eye. This report includes
      prevalence data on 21,585 persons enrolled in this review still alive and living
      in Israel in 2003. We estimated the prevalence rate of blindness nationwide and
      the incidence rate for each cause of blindness for every year. RESULTS: The main
      leading causes of blindness in Israel in 1998 were (in percent of the total
      number of newly registered patients): age-related macular degeneration (20.1%),
      glaucoma (13.8%), myopic maculopathy (12%), cataract (10.4%), diabetic
      retinopathy and maculopathy (10.1%), and optic atrophy (7.9%), and in 2003, 28%,
      11.8%, 7.4%, 6.5%, 14.4% and 6.5% respectively. CONCLUSIONS: The results indicate
      that the incidence of age-related macular degeneration, diabetic retinopathy and
      maculopathy in Israel is increasing, while that of glaucoma, myopic maculopthy,
      optic atrophy and cataract is decreasing.

PMID- 17214112
TI  - Stress fracture of the ulna in a military recruit.

PMID- 17214113
TI  - Postpartum group B streptococcal tricuspid valve endocarditis.

PMID- 17214114
TI  - Plantar verrucous carcinoma (epithelloma cuniculatum): rare form of the common
      wart.

PMID- 17214115
TI  - Acute confusion in an elderly woman with Rendu-Osler-Weber disease.

PMID- 17214116
TI  - Penile gangrene due to severe vascular calcification.

PMID- 17214117
TI  - Intensive lipid-lowering therapy: obvious benefits, possible risks.

PMID- 17214118
TI  - Sexually transmitted infections among individuals with and without HIV.

PMID- 17214119
TI  - Tube feeding of the terminally demented patient.

PMID- 17214120
TI  - Treaties and tuberculosis: First Nations people in late 19th-century western
      Canada, a political and economic transformation.
AB  - This paper examines the explosion of tuberculosis infections among First Nations
      communities of western Canada during the critical period from Canada's
      acquisition of the Northwest to the early 1880s. In the early 1870s, the disease
      was relatively rare among the indigenous population of the plains. Within a few
      years, the situation changed dramatically. By the early 1880s, TB was widely
      recognized to be the primary cause of morbidity and mortality among First Nations
      populations. Rather than direct infection from the burgeoning European population
      in the region, the explosion of the disease was caused by sudden ecological,
      economic, and political changes in the west that were primarily the result of the
      imposition of Canadian hegemony.

PMID- 17214121
TI  - [Medical libraries in Quebec of the 18th and 19th centuries: the example of
      tuberculosis].
AB  - Phthisis (tuberculosis) became so prevalent in Europe in the 18th century that,
      in 1792, Antoine Portal wrote: "there is no disease more common or dangerous than
      pulmonary phthisis." Obviously, the doctors were concerned about this problem and
      made efforts to explain it. Numerous hypotheses were advanced on this subject
      (Richard Morton, for instance, suggested 12 possible causes in his
      Phthisiologia), and varied by author and region, but they can be grouped into
      four main categories: a contagious disease; a hereditary condition; a
      physiological disorder; and a problem resulting from lifestyle. This research
      concerns the books on this disease procured by medical practitioners in and
      around Quebec City in the 18th and 19th centuries, dating from 1700-1868, and
      contained in 27 medical libraries. Following a brief presentation of methodology
      and the libraries, this article analyzes the books. There were books on phthisis
      in Quebec City very early in the 18th century, although the majority appeared in
      the next century. The 18th-century works associated this disease with
      physiological disorders--particularly "mechanical problems." After 1815, there
      was a broader diversity of opinions. The books on phthisis most widely consulted
      from 1700 to 1868 are almost completely unknown today.

PMID- 17214123
TI  - Disease and domesticity on display: the Montreal Tuberculosis Exhibition, 1908.
AB  - This article explores ideas about tuberculosis in early 20th-century Montreal by
      looking at one particular event: The Montreal Tuberculosis Exhibition of 1908. An
      analysis of the layout and design of this exhibition reveals that objects were
      manipulated to convey specific messages. Domestic spaces were showcased as being
      particularly troublesome. The exhibition suggested that the home was a
      potentially dangerous agent of disease, thereby revealing a relationship between
      disease and everyday life.

PMID- 17214122
TI  - "The tubercular cow must go": business, politics, and Winnipeg's milk supply,
      1894-1922.
AB  - This paper analyzes the Winnipeg health department's campaign to eliminate
      tuberculosis in dairy herds supplying milk to the city. It examines the
      complexity of creating dairy policies at a time when there was no consensus about
      the role that Mycobacterium bovis played in the etiology of tuberculosis in
      humans, and when dairy producers and consumers often resisted regulations that
      increased their costs. The article argues that the scientific debates about the
      regulation of the city's milk supply enabled physicians and veterinarians to
      enlarge their professional practices; that the benefits and costs of the dairy
      policies were not equally distributed; and that Winnipeg's milk supply remained
      vulnerable to both deliberate and accidental contamination throughout this
      period.

PMID- 17214124
TI  - Containing and preventing contagious disease: Montreal's Protestant school board
      and tuberculosis, 1900-1947.
AB  - In this period, Montreal was the most unhealthy city in Canada owing to
      widespread poverty, abysmal living conditions, inadequate public health, and a
      dependence upon private charities to provide health and welfare services. While
      Montreal's Protestant school board assumed a pivotal role in the war on
      tuberculosis by early identification of consumptive pupils, educating those in
      treatment, and prevention, these initiatives were tempered by a conservative view
      that equated poverty with moral degeneration. School board minutes provide a
      window onto commissioners' construction of health, the nature of the relationship
      between a school and its community, and the factors which influenced their
      decisions.

PMID- 17214125
TI  - "Not a shack in the woods": architecture for tuberculosis in Muskoka and Toronto.
AB  - This paper explores architecture as a primary source in the history of
      tuberculosis. In comparing five Ontario sanatoria built between 1897 and 1923, we
      identify a range of types and a growing resemblance of ex-urban TB sanatoria to
      urban hospitals. Existing literature on Canadian TB hospital architecture
      suggests the endurance of picturesque architecture, but the cottage plan was only
      one of the types deemed appropriate for consumptives in the early 20th century,
      even in Muskoka. Furthermore we argue that urban and ex-urban TB ideologies
      actually coalesce about 1923, best illustrated in the boldly modern architecture
      of Muskoka's new Gage pavilion.

PMID- 17214126
TI  - The evolution of the sanatorium: the first half-century, 1854-1904.
AB  - In the 19th century tuberculosis was the major threat to health in Europe and
      North America. It was thought to be caused by heredity compounded by one's way of
      life and, even when proved to be an infection, these factors were thought to
      identify who would catch it. In 1854 Hermann Brehmer asserted that he could cure
      tuberculosis with a regimen of fresh air, exercise and good nutrition in a
      sanatorium. Although the medical establishment initially rejected Brehmer's ideas
      the sanatorium movement steadily caught hold, and within two decades was
      supported by eminent physicians. Rest replaced Brehmer's exercise, as the key
      remedy. The sanatorium regimen put Galenic principles of hygiene into practice.

PMID- 17214127
TI  - Medicine circles defeating tuberculosis in southern California.
AB  - In the late 19th and early 20th centuries, two medicine circles existed in Indian
      country: one Native and one Euro-American. Traditional doctors among First
      Nations peoples approached disease in spiritual ways and also used herbal
      medicine to treat their patients. First Nations people tried to treat infectious
      diseases brought by newcomers through plant medicine, ritual, and ceremony.
      Generally unsuccessful, First Nations people and doctors of California learned
      from practitioners of Western medicine to care for tubercular patients, to avoid
      the bacteria, and to remove active tubercular patients to sanatoria. Native
      agency and Western medical practices intersected and worked successfully from
      1928-48 to reduce cases and deaths caused by tuberculosis.

PMID- 17214129
TI  - "Lo! The poor Indian!" colonial responses to the 1862-63 smallpox epidemic in
      British Columbia and Vancouver Island.
AB  - The smallpox epidemic that swept through the colonies of Vancouver Island and
      British Columbia in 1862-63 was particularly devastating to the First Nations of
      the region. Colonists responded to the developments with a mixture of pity,
      revulsion, a smug sense of inevitability, and, above all, an overriding concern
      for their own self-interest. The colonial population may not have consciously
      attempted to devastate the First Nations populations, but their frequently
      negative attitudes towards them ensured that actions to prevent this occurrence
      were sporadic, poorly planned, counterproductive, or simply minimal.

PMID- 17214128
TI  - [The anatomical-clinical conceptualisation of pulmonary tuberculosis in the work
      of Laennec].
AB  - The present study discusses the description of the tubercules of the lung which
      appeared in the 1826 edition of the treatise De l'auscultation mediate (1819) by
      Laennec, the author with Bayle of the first anatomo-clinical conceptualisation of
      pulmonary tuberculosis. Employing the analytical framework developed by Othmar
      Keel, the study investigates the interrelationships between two contemporaneous
      modes of interpreting the pathological evidence--the localist vision and the
      anatomo-pathological conception--in order to understand the influences of the
      surgical model upon the progress of anatomical, physiopathological, and tissue
      investigations by researchers such as Hunter and Bichat.

PMID- 17214130
TI  - Beethoven's terminal illness and death.
AB  - There is dispute about the cause of Beethoven's death; alcoholic cirrhosis,
      syphilis, infectious hepatitis, lead poisoning, sarcoidosis and Whipple's disease
      have all been proposed. In this article all primary source documents related to
      Beethoven's terminal illness and death are reviewed. The documents include his
      letters, the report of his physician Andreas Wawruch, his Conversation Books, the
      autopsy report, and a new toxicological report of his hair. His terminal illness
      was characterised by jaundice, ascites, ankle oedema and abdominal pain. The
      autopsy data indicate that Beethoven had cirrhosis of the liver, and probably
      also renal papillary necrosis, pancreatitis and possibly diabetes mellitus. His
      lifestyle for at least the final decade of his life indicated that he
      overindulged in alcohol in the form of wine. Alcohol was by far the most common
      cause of cirrhosis at that period. Toxicological analysis of his hair showed that
      the level of lead was elevated. During the eighteenth and early nineteenth
      centuries, lead was added illegally to inexpensive wines to sweeten and refresh
      them. These findings strongly suggest that liver failure secondary to alcoholic
      cirrhosis, associated with terminal spontaneous bacterial peritonitis, was the
      cause of death. This was complicated in the end stages by renal failure. If the
      presence of endogenous lead was verified by analysis of Beethoven's skeletal
      remains, it would suggest that the lead was derived from wine that he drank. Lead
      poisoning may account for some of his end-of-life symptoms. There is little
      clinical or autopsy evidence that Beethoven suffered from syphilis.

PMID- 17214131
TI  - What became of Arthur Conan Doyle's father? The last years of Charles Altamont
      Doyle.
AB  - This paper examines the fate of Arthur Conan Doyle's father, Charles Altamont
      Doyle, a Victorian illustrator, who spent his last years as an asylum inmate.
      Based on new archival research, it looks at the reasons for his
      institutionalisation and what befell him during his stay. It will consider
      Doyle's claim that he was wrongfully confined and also the suggestion that his
      family were responsible for having him committed. Finally, the paper will examine
      the nature of Doyle's condition and the creative work he produced whilst an
      asylum inmate.

PMID- 17214133
TI  - [Abortion in the Castilian medical literature of the 16th century].
AB  - This article analyzes the causes of abortion according to the medical and
      surgical literature that circulated in Castilian in the fifteenth and sixteenth
      centuries. These works not only explain the medical causes of the death of
      foetuses but also show how female health was discriminated against and how
      doctors were able to produce an incipient causal theory in accordance with the
      medical and social problems of their time.

PMID- 17214132
TI  - [Medicine and astrology in Arnau's corpus].
AB  - The role of astrology in Arnau de Vilanova's medical work is revisited with
      special attention to the problems of authorship posed by the astrological
      writings of Arnau's corpus and to their hypothetical chronology.

PMID- 17214134
TI  - [Simon de Tovar (1528-1596): family networks, American nature and trade in
      curiosities in 16th century Seville].
AB  - The central character of this work is Simon de Tovar, a citizen of late 16th
      century Seville, who was an outstanding collector of American plants. Beyond the
      traditional historiography of early modern Spanish botany, Tovar's activities
      have been set in the context of an expanding trade in marvels and curiosities.

PMID- 17214135
TI  - [At the centre of all gazes: an approach to the historiography of phrenology].
AB  - Since the late 19th century, phrenology has been regarded at best as a pseudo
      science popularised by quacks. During the 1970s, representatives of the new
      social history of science and medicine chose it as their favourite target for the
      in-depth construction of scientific orthodoxy. Since then, different approaches
      to phrenology have helped to change a 19th century view focused on the emergence
      of science as a profession and on the new technical nature of medicine. In this
      paper, I analyse the different contributions to the study of phrenology in Great
      Britain and France over the past three decades and point out some aspects that
      should receive more attention in future research.

PMID- 17214136
TI  - [Romantic magnetism: The patient. The woman. The republic].
AB  - This paper, based on case studies, aims to present some aspects of the animal
      magnetism that developed in the Germany of the first decades of the nineteenth
      century. These aspects constitute, or at least imply, important innovations
      within the framework of contemporary medical practice and consist of: the
      recognition of the importance of the words of patients and their own knowledge of
      their bodies; the emergence of the figure of woman as an independent and singular
      subject in which the aspects indicated above are emphasized; and, finally, the
      latent potential of this medical theory for reform within the framework of
      policy.

PMID- 17214137
TI  - [The Union Medica Hispano-Americana (1900) and its contribution to scientific
      internationalism].
AB  - The Union Medica Hispano-Americana was founded during the XIII International
      Congress of Medicine of Paris in 1900. Its main aim was to strengthen the
      cultural and scientific ties among Spanish speaking countries. The first assembly
      took place in Madrid in the Spring of 1903. The most interesting paper presented
      was undoubtedly that of Manuel Tolosa Latour. He suggested creating a Diccionario
      Tecnologico Medico Hispano-Americano. The society had no continuity and neither
      did the dictionary. The reasons for this failure must be seen in the absence of
      economic support by political authorities in Spain and America, the
      organizational weakness of the Union and the poverty of its action program, which
      was imbued with a triumphalist rhetoric, empty of content and highly
      paternalistic in its relations with the American world.

PMID- 17214138
TI  - [The medical and pharmaceutical profession and the mutual care system in the
      writings of Jaime Vera (1859-1918)].
AB  - This article presents the perspectives of the physician and politician Jaime Vera
      y Lopez (1859-1918), co-founder of the Spanish Socialist Workers' Party, on the
      medical profession, medical practice, and healthcare systems. It compares the
      Report (Informe) that he presented to the Comision de Reformas Sociales (1884)
      with his later writings published in the socialist press ("Farmacia y cooperacion
      obrera,, 1914 and "La locura en los ninos. Camino del remedio", 1916). We observe
      the discrepancies between the political-programme documents and the articles
      centring on professional questions and highlight how his theoretical focus is
      modified when applied to matters of medical practice.

PMID- 17214139
TI  - [Towards a new social perception of people with disabilities: legislation,
      medicine and the work-disabled in Spain (1900-1936)].
AB  - This paper aims to analyse the role played by Medicine, against a background of
      social reform in the first third of the 20th Century, in helping to shape the
      nature of disabilities in Spain. We look at the legislation passed to regulate
      occupational accidents and the institutions set up to look after accident victims
      with physical or functional disabilities from the perspective developed in the
      new academic field of disability studies and using scientific and professional
      journals as well as documentation from Spain's legislative chambers as our main
      sources. We attempt to examine the extent to which these developments helped to
      transform the existing social perception of people with disabilities.

PMID- 17214140
TI  - "A century of civilization under the influence of eugenics": Dr. Enrique Diego
      Madrazo, socialism and scientific progress.
AB  - This article discusses the thought of one of the pioneers of eugenics in Spain,
      Dr. Enrique Diego Madrazo. In particular, it analyses his 1930 essay Un siglo de
      civilizacion bajo la influencia eugenesica [A Century of Civilization under the
      Influence of Eugenics], as the most explicit work on the eugenic utopia he
      advocated. This work, because of its breadth, was also one of the most extensive
      and detailed accounts of the steps to be taken towards the eugenic society that
      was produced. The present analysis of his work assesses the degree to which his
      thought, which has been described as "utopian socialist", in fact corresponded to
      that epithet, given the politically authoritarian nature and the gender bias of
      some aspects of his one-hundred year plan for the creation of a eugenic society.
      The article also places Madrazo's thought in the context of his time and other
      national currents of eugenic thought.

PMID- 17214141
TI  - ["Two professions for a single task". The introduction of chemical engineering in
      Spain during the first Francoism].
AB  - Through the first half of the 20th century, chemical engineering was established
      as an academic option in the training of specialists for the North-American and
      European chemical industry, whereas it was not a special field of study in Spain
      until the 1990s. The reason for this delay was a battle of interests between
      chemist and industrial engineers to control this career during the first
      Francoism. This article will try to show the development and professionalization
      of specialists for the Spanish chemical industry.

PMID- 17214142
TI  - Reconstructing data: evidence-based medicine and evidence-based public health in
      context.
AB  - The emergence of Evidence-Based Medicine (EBM) as the gold-standard practice in
      biomedicine and public health practices represents a significant epistemological
      turn in modern medicine. The development of Evidence-Based Public Health (EBPH)
      followed the emergence of Evidence-Based Medicine, as an attempt to ground health
      policies and interventions on "sound facts". The present paper analyzes the
      historical and sociological roots of this turn. We evaluate the ethical and
      social consequences of this transformation, both within the medical profession
      (the polarization between a medical elite which strengthened its professional
      status, and a rank and file which experienced a process of "de
      professionalization") and in its relationship to the welfare state (the link
      between the medical elite, EBM, EBPH and the commodification of health care and
      public health).

PMID- 17214143
TI  - [The chemical revolution: between history and memory].

PMID- 17214144
TI  - Focal lesions of the spleen in patients with fever of unknown origin: sonographic
      patterns and diagnosis.
AB  - A review of ultrasonic scans performed for 811 patients admitted at the Abbassia
      Fever Hospital between 1990 through 1996 for investigation of fever undiagnosed
      for over 3 weeks revealed 28 cases of focal splenic lesions. They included
      lymphoma in sixteen cases, tuberculosis in six cases, echinococcal cysts in
      three, abscess in two, and infarction in one. Final diagnosis was obtained by
      correlating the ultrasonography and clinical findings, together with pathologic,
      bacteriologic, serologic and angiographic data.

PMID- 17214145
TI  - Enteroviruses in sewage: comparison of different technologies for wastewater
      treatment and reuse.
AB  - Seven wastewater treatment plants were twice sampled to compare their different
      technologies for the removal of enteroviruses. These technologies are extended
      aeration, oxidation ditch, stabilization pond, aerated stabilization pond,
      submerged fixed film reactor, trickling filter and trickling filter followed by
      activated sludge in El-Serw, El-Rahamna, El-Adliya, Daqahla, El-Barashiya, Sohag
      and El-Fayoum wastewater treatment plants, respectively. Virus counts of raw
      sewage ranged between 2.7 x 10(3) and 20 x 10(3) PFU/L and for treated effluents
      was between 0 and 6 x 10(3). The percentage of virus removal was varied where
      trickling filter and tickling filter followed by activated sludge reduced virus
      counts by 95.7 and 99.9, respectively. Extended aeration removed 64.2%, oxidation
      ditch 66.5%, stabilization pond 44.9%, aerated stabilization pond 13.34%, and
      submerged fixed film reactor removed 53.4%. The neutralization test revealed five
      types of enteroviruses, poliovirus types 1,2 and 3 and Coxsackievirus types B4
      and B5. The isolated polioviruses were vaccine strains. From the frequency
      distribution of the detected viruses, poliovirus type 2 was the most dominant.

PMID- 17214146
TI  - New approaches to virus removal: the way to produce virus-free drinking water.
AB  - Virus control in drinking water is considered one of the serious problems to be
      encountered in the near future. Trials to remove viruses from drinking water were
      directed to enhance water treatment processes, use of different disinfectants or
      use of a good virus adsorbent material. In the present study, four materials were
      prepared, dimethylaniinoethyl chitin, chitosan and cellulose and starch acrylate
      and examined for adsorption of hepatitis A virus from drinking water. Also, three
      types of eluates (3% beef extract-glycine, 3% beef Virus control in drinking
      water is considered one of the serious problems to be encountered in the near
      future. Trials to remove viruses from drinking water were directed to enhance
      water treatment processes, use of different disinfectants or use of a good virus
      adsorbent material. In the present study, four materials were prepared,
      dimethylaniinoethyl chitin, chitosan and cellulose and starch acrylate and
      examined for adsorption of hepatitis A virus from drinking water. Also, three
      types of eluates (3% beef extract-glycine, 3% beef extract and glycine) were used
      for virus recovery from adsorbed materials. The results obtained showed that
      dimethylaminoethyl chitosan was a good adsorbent (99.16%) and the three eluents
      were poorly desorb viruses.

PMID- 17214147
TI  - Histamine content in sardine and its products.
AB  - A total of 80 random samples of fresh sardines, salted sardines, locally canned
      sardines and imported canned sardines (20 from each) were collected from fish
      markets and shops in Alexandria governorate. The collected samples were analyzed
      for determination of histamine level by Thin Layer Chromatography. The results
      revealed that the highest histamine content was observed in locally canned
      sardines and decreased gradually in salted sardines, imported canned sardines and
      fresh sardines. The percentages of the examined sardine samples having a higher
      histamine content than the permissible limit were 5%, 10%, 10% and 5% for fresh,
      salted, locally canned and imported canned sardines, respectively. The health
      hazard as well as the suggestive measures for controlling the histamine content
      in sardine and its products are discussed.

PMID- 17214148
TI  - Prevalence of schistosoma mansoni and intestinal parasites with evaluation of
      hepatic schistosomiasis in a rural area after governmental efforts (Gharbia
      governorate).
AB  - The study was carried out on 2136 individuals from Abo El-Gohoor village. Their
      ages ranged from 1-72 years with a mean of 28.3 +/- 22.4 years. They were 46.7%
      males and 53.3% females. The village was divided into sectors. The inhabitants of
      each sector were examined clinically with history taking through home visits.
      Three successive stool samples for each individual were examined by the
      concentration technique. Abdominal ultrasound was done for hepatic and splenic
      assessment. Rectal biopsy was done for 200 subjects with negative stool samples
      for Schistosoma mansoni (S. mansoni) ova. Sex distribution was equal in this
      group. Their ages ranged from 18 to 45 years with a mean of 30.1 +/- 9.5 years.
      S. mansoni prevalence was 19.3% of individuals through stool examination and
      12.5% out of 200 individuals with active schistosomiasis after rectal biopsy (the
      total prevalence was approximately 29.4%). Hepatic schistosomiasis was 18.8%.
      Hepatomegaly, hepatosplenomegaly, hepatic fibrosis without and with ascites were
      6.0%, 8.8%, 2.5% and 1.5% of examined patients, respectively. The prevalence of
      intestinal parasites was 37.5% and 27.8% for E. histolytica and G. lamblia,
      respectively, 9.2% for H. nana, 6.2%, 9.6%, 2.4% and 1.5% for A. lumbricoides, E.
      vermicularis, T. trichura and A. duodenale, respectively and F. gigantica was
      0.4%. A total of 84.6% of examined subjects had parasitic infestations, 60.2% had
      one parasite, 19.6% had 2 parasites, 4.2% had 3 parasites and 0.7% had 4
      parasites. The study revealed some success of governmental efforts for control of
      schistosomiasis. The prevalence of S. mansoni through stool examination showed a
      prevalence lower than that reported before but which does not represent the
      actual prevalence of S. mansoni and rectal biopsy in addition gave more accurate
      results.

PMID- 17214150
TI  - Genetic study of epilepsy.
AB  - This study comprised 32 patients with epilepsy. They were referred to the Human
      Genetics Department, Medical Research Institute, Alexandria University, Egypt.
      They were mentally retarded with the exception of three patients who had normal
      mentality. Their ages ranged from 2 months to 16 years. Females and males were
      equally affected (M/F=1). All patients were evaluated to identify the specific
      etiology of epilepsy. They were classified into symptomatic generalized epilepsy
      (29 cases) and idiopathic generalized epilepsy (3 cases). After evaluation they
      were classified according to their diagnosis into those displaying mendelian
      inheritance, norunendelian inheritance and chromosome disorders. The symptomatic
      group showed a mendelian inheritance and chromosomal aberrations while the
      idiopathic group showed a nonmendelian inheritance.

PMID- 17214149
TI  - Biological monitoring of occupational exposure to benzene and toluene.
AB  - This study was carried out to evaluate the biological monitoring of occupational
      exposure to benzene and toluene in a total number of 31 male exposed workers and
      30 control subjects. The present study showed a statistically significant higher
      level of biological indices of exposure (p < 0.01) of phenol and hippuric acid in
      urine of workers exposed to benzene and toluene than control subjects.
      Significant changes (p < 0.05, 0.01) in the levels of hematological and
      biochemical findings have been observed among exposed workers and control group.
      In addition, statistically significant higher levels of Mg, Mn and Ca were found
      among workers exposed to benzene and toluene while statistically significant
      lower levels of serum iron (p < 0.05) have been observed. No significant
      variations could be detected in the level of Zn and Cu between exposed and
      control subjects.

PMID- 17214151
TI  - Poliomyelitis, measles and neonatal tetanus: a hospital based epidemiological
      study.
AB  - Vaccine-preventable diseases constitute a major health problem contributing to
      the morbidity and mortality in many developing countries including Egypt. WHO
      adopted resolutions to eradicate poliomyelitis by the year 2000, eliminate
      neonatal tetanus by the year 1995, and reduce measles mortality by 95% and
      morbidity by 90%, compared to the pre-immunization levels by 1995. Evaluation of
      preventive programs for these diseases necessitates availability of up to date
      information on their occurrence. The present study was undertaken to determine
      the current epidemiological features of poliomyelitis, neonatal tetanus and
      measles, to identify the trends of these diseases as well as to determine their
      outcomes and hospital loads. Data about the admitted cases of poliomyelitis,
      neonatal tetanus and measles were collected from the hospital register of
      Alexandria fever hospital for five successive years (1992-96). Available
      information on age, sex, residence, diagnosis, outcome of treatment, dates of
      admission and discharge were collected. The total number of cases of the three
      diseases admitted to the hospital during the period 1992-96 were 1406, measles
      represented 85.4%, neonatal tetanus 13.9% and poliomyelitis 0.7%. The results
      revealed that in the year 1994 only one case of poliomyelitis was admitted and
      since then no other cases were reported. The number of measles cases increased
      gradually in the latter years and about 78% of them were older than five years of
      age. A significant increase in the age of measles occurrence was observed. A
      gradual decline in the number of neonatal tetanus cases was observed. These cases
      were more apt to occur among early neonates but still clustered in certain
      geographical areas. The results of the study pinpoint the long term impact of the
      well run program aiming at eradicating poliomyelitis in Alexandria. However, for
      elimination of neonatal tetanus and controlling measles morbidity, further
      activities are required including strengthening the surveillance activities for
      detection of the high risk geographical areas and the high risk factors.

PMID- 17214152
TI  - Biochemical and virological response (by PCR) to interferon therapy in chronic
      hepatitis C.
AB  - Interferon-alpha has been established for the treatment of chronic hepatitis C
      virus infection. However, the complete responding rate is not higher than 20-25%.
      Our study was carried out on sixty patients with chronic HCV infection with the
      following criteria: elevated serum ALT levels, positive antibodies to HCV (by
      second generation ELISA and RIBA tests) and positive HCV in serum by PCR. All
      patients had negative tests for hepatitis B virus and liver histopathological
      findings consistent with chronic hepatitis +/- cirrhosis. Patients were treated
      with 3 Mu interferon-alpha thrice weekly for 6 months. The results showed
      response in 14 out of the 60 patients (23.3%) with normalization of the ALT
      levels within 2-3 months of IFN therapy. Complete response (CR) was present in
      6/14 (42.9%) of the responders with negative PCR in serum up to 6 months after
      stoppage of therapy. Response with relapse (unsustained response) was noticed in
      8/14 (57.1%) of the responders with elevation of ALT level 2 months after
      stoppage of treatment. Forty six patients 46/60 (76.7%) were non-responders (NR)
      with significant elevation of ALT level and positive PCR in serum all through the
      course of treatment. The response in cirrhotic patients was significantly lower
      than in noncirrhotic cases. In conclusion, prolonged treatment courses should be
      further evaluated in controlled studies.

PMID- 17214153
TI  - Association of hepatitis C virus with liver cirrhosis and hepatocellular
      carcinoma compared with hepatitis B virus in Egyptian patients.
AB  - Hepatocellular carcinoma (HCC) is an aggressive malignancy and carries a poor
      prognosis. Documentation of the wide geographical variation in its incidence has
      led to clear identification of several risk factors. These include hepatitis B
      virus (HBV) and hepatitis C virus (HCV) infections in endemic areas. The present
      study investigated the association of HBV with HCV and cirrhosis, the latter is
      regarded as a premalignant lesion and underlies most cases with HCC. Serum
      samples from 94 patients with HCC (n=25) and cirrhosis (n=69) were tested for
      hepatitis C virus antibody (anti-HCV), hepatitis B surface antigen (HBsAg),
      hepatitis B core antibody (anti-HBc) and serum alphafetoprotein (AFP). Of the 94
      patients, 71 (75.5%) had anti-HCV, 6 (6.4%) were positive to HBsAg, while 64
      (68.1%) were positive to anti-HBc. These viral markers were more prevalent among
      HCC patients, 19 (76.0%) had hepatitis C antibody, 3 (12.0%) were positive to
      HBsAg and 22 (88.0%) were positive to anti-HBc compared with 52 (75.4%), 3 (4.3%)
      and 42 (60.9%), respectively in patients with cirrhosis. Regarding serum AFP
      measurement, 14 (56%) of patients with carcinoma and 35 (50.7%) of patients with
      cirrhosis demonstrated levels above 7 ng/ml. In patients with cirrhosis, elevated
      serum AFP and presence of anti-HCV in serum were significantly associated. In
      conclusion, this study shows that viral hepatitis is strongly associated with the
      development of cirrhosis and HCC in Egyptian patients. Hepatitis C virus seems to
      play a predominant role compared with hepatitis B virus.

PMID- 17214154
TI  - Chromosome anomalies in normal androgenized infertile males.
AB  - Chromosome anomalies are known to play a role in human infertility. Chromosome
      analysis of 103 normal androgenized infertile azoospermic (97.1%) or oligospermic
      (2.9%) males revealed that the frequency of chromosomal abnormalities was 8.7%.
      Two patients (1.94%) had a 46,XX chromosome complement, one patient (0.97%) had a
      45,X karyotype, two patients (1.94%) had a 45,XY,t(13;14)(p11;q11) karyotype, one
      patient (0.97%) had a 46,XY,inv(9)(p12;q13) chromosome constitution, two patients
      (1.94%) had a 46,XY,del(Y)(q12) karyotype, and one patient (0.97%) had a
      45X/46,X+marker the nature of which was not clarified.

PMID- 17214155
TI  - Campylobacter diarrhea in Alexandria, Egypt.
AB  - The role of Campylobacter as a cause of bacterial diarrhea in young children in
      Alexandria, Egypt was investigated. Stools or rectal swabs were collected from
      880 children (mean age 9.8 months) presenting to a hospital with the primary
      complaint of diarrhea and from 1,079 well children (mean age 8.8 months)
      attending a vaccination clinic. Isolation of Campylobacter was significantly
      (p<0.0002) more frequent from cases (17.2%) than from controls (6.4%).
      Campylobacter was isolated from children presenting with diarrhea more frequently
      than Salmonella (3% isolation rate), Shigella (2% isolation rate), or other
      bacterial pathogens (1% isolatoin rate). Isolation of Campylobacter was
      significantly more frequent during the rainy season (p<0.0012). These results
      implicate Campylobacter as a major bacterial cause of diarrhea for which young
      children are brought for medical attention in Alexandria, Egypt.

PMID- 17214156
TI  - Detection of hepatitis B virus DNA by in situ tissues hybridization in corneal of
      HBsAG positive donors.
AB  - HBV is a hepatotropic virus. The highest concentration found in the blood and
      liver with lower amount in saliva and semen. The virus was also detected in body
      fluids. Keratoplasty is an essential operation for the treatment of corneal
      blindness. At Ain Shams University International Eye Bank 10% of the collected
      corneas were from donors with HBs antigenemia. These corneas were rejected
      according to the Eye Bank Association of America. In this study 32 corneal
      tissues of 16 donors positive HBsAg were examined for,the presence of HBV by in
      situ DNA hybridization technique to detect HBV DNA in the corneal sections. This
      marker could not be seen in this work. This preliminary study could be an
      encouraging step for further researches to evaluate the possibility of the
      avascular cornea to carry HBV.

PMID- 17214158
TI  - Bacteriologic potability of the drinking water in a diarrhea hyperendemic area in
      southwestern Saudi Arabia.
AB  - High prevalence of diarrhea was reported among people living in a semiurban
      community in Shebaa area in Southwestern Saudi Arabia. This was in comparison to
      prevalence in a nearby urban community in Abha, the capital city of The
      Southwestern Region of Saudi Arabia. Contamination of the desalinated water,
      commonly used for drinking, was one possible hypothesis for occurrence of this
      diarrhea problem. The objective of the present study was to test bacteriological
      potability of desalinated water in both Shebaa and Abha areas and to determine
      whether any contamination occurred during transportation from water distribution
      stations to houses or during storage in house reservoirs. Water samples were
      collected and analyzed by the Presumptive Coliform Test from a sample of water
      tankers transporting water and from tap water originating from house reservoirs
      in a sample of houses in the two areas. Source of drinking water was recorded for
      each of such houses. Of 117 water samples from 39 tankers transporting water,
      only one sample was positive bacteriologically and non-potable (potability =
      99%). Whereas among 201 tap water samples from a random sample of houses, 26.4%
      showed contamination. Bacteriological non-potability was found in a significantly
      higher proportion of houses in Shebaa area (38.4%) than in Abha city (7.9%),
      (p<0.001). Also, desalinated water was used for drinking significantly more in
      Shebaa than in Abha (p<0.001). It is concluded that transportation of the
      desalinated water by water tankers has not significantly contributed to its
      contamination. Such contamination rather obviously occurred during storage in
      house reservoirs, and was possibly implicated, at least partly, in the increased
      prevalence of diarrhea in Shebaa.

PMID- 17214157
TI  - Hyperendemicity of diarrhea in a valley area, Asir Region, southwestern Saudi
      Arabia.
AB  - A random sample of 781 subjects living around a valley in Shebaa area,
      southwestern Saudi Arabia, and 1284 subjects from the rest of Shebaa, along with
      a sample of 1095 from a nearby urban community in Abha city have been studied
      following a notification of a suggestive increase of diarrhea in the valley. This
      was to determine whether the prevalence of diarrhea was high in the valley and to
      formulate hypotheses about possible implicated factors. The family head was
      interviewed about episodes of diarrhea among family members during the 2-week
      period preceding the interview, about source of drinking water, and about some
      demographic variables. Observations were made and data were collected on presence
      and frequency of flies in the house, methods of excreta and refuse disposal,
      valley and wells water, and the nearby agricultural farms. The 2-week diarrhea
      episode rate per subject was significantly (p<0.0001) highest in the valley
      (0.20), was 0.09 in the rest of Shebaa, and was lowest in the urban community
      area. (0.05). The rate decreased by age (p<0.001) and increased by frequency of
      flies in the house (p<0.0001), particularly in the valley. Drinking only from the
      desalinated water was associated with diarrhea episode rate of 0.12 as compared
      to 0.05 for drinking only from bottled water or from any other combination of
      sources (p<0.01). The valley and wells water was grossly polluted and was
      regularly used for irrigating and washing fresh fruits and vegetables from nearby
      farms. Hypotheses for the factors possibly contributing to this hyperendemicity
      of diarrhea in the valley include inadequate excreta and refuse disposal,
      contamination of the valley and wells water, contamination of the desalinated
      water during transportation or storage and abundance of flies.

PMID- 17214160
TI  - Use of breast feeding indicators for assessment of current feeding practices.
AB  - To investigate the current breast feeding practices, a survey was conducted cross
      sectionally on 2000 children aged less than 2 years recruited from 6 MCH centers
      in Alexandria governorate. The median duration of breast feeding was 19.4 months.
      Only one quarter of infants were exclusively breast fed for the first four months
      of age with a mean duration of 2.4+2.5 months. Predominantly breast feeding rate
      was 0.36, while timely complementary breast feeding rate(6-9 months) was 0.66.
      Continued breast feeding rate(one year) was 0.73 while that for two years was
      0.3. Results also indicated that 40% of infants were receiving food from a bottle
      with a nipple/teat regardless of whether or not the infant was breast fed. These
      findings implicate that promotion of breast feeding should receive priority in
      health programs activities.

PMID- 17214159
TI  - An epidemiological study on consanguineous marriage among urban population in
      Alexandria.
AB  - The study was carried out using a cross-sectional approach, involving interviews
      with 500 households randomly selected from three urban areas in Alexandria (Bab
      Sharki, El Gomrok and Karmouz). A questionnaire interview was conducted with
      married females in these households to determine prevalence of consanguineous
      marriages and to study knowledge of married females about causes and effects of
      consanguineous marriages. Prevalence of consanguineous marriages among 500
      married females was 22.8% with the highest frequency among marriage between first
      cousins (15.8%). Average inbreeding coefficient up to the marriage between second
      cousins equals to 0.01172. The linear trend of consanguineous marriages
      throughout the last 50 years was statistically significant. Age at marriage was
      younger in consanguineous marriages than non consanguineous marriages.
      Longstanding familiarity and sharing same traditions and customs with male
      relatives were the main causes of consanguineous marriages. The majority of the
      studied females (42.2%) reported that consanguineous marriage is harmful while
      29.6% reported that it has no effect on offsprings.

PMID- 17214161
TI  - Comparison of the life table characteristics of Anopheles sergentii (Diptera:
      Culicidae) from two malarious areas in Egypt.
AB  - Life table characteristics were examined for the malaria vector, An. serenti from
      two Faiyum villages: Tersa (T) and El Nazlah (N) from Siwa oasis (Sw) under
      constant laboratory conditions at 25 degrees C and 70% RH. Females of T, N and Sw
      completed 4, 5, and 2 gonotrophic cycles (gc) respectively. The first gc required
      a significantly longer period (p<0.05) than the subsequent ones. Development
      times for Sw immatures were longer (p<0.05) than for the other colonies. Life
      expectancies at emergence for males of the 3 colonies were significantly shorter
      than for their respective females. Generation time was shorter (p<0.05) for T
      (mean = 31.15 days) than for Sw (37.81 days) or N (43.64 days) colonies. The
      birth rate of Sw colony (mean = 0.33 female female/female) was significantly
      higher (p<O.05) than those of the other colonies. The other biological
      parameters: fecundity, egg hatch times and rates, survivorship from egg eclosion
      to adult emergence, male and survivorships, net reproductive rate, intrinsic rate
      of increase all showed no colony variations. The study concluded that variation
      among colonies in certain biological aspects may not reflect strain differences.

PMID- 17214162
TI  - Role of cytomegalovirus in inducing congenital anomalies.
AB  - Sixty eight infants and newborns were included in the present study being
      consisted of 55 cases with congenital anomalies and 13 cases of apparently
      healthy infants acting as controls. Three types of congenital anomaly cases were
      studied; 17 cases of microcephaly, 17 cases of cerebral palsy and 21 cases with
      jaundice. All serum samples were tested for cytomegalovirus IgM antibodies (CMV
      IgM) by microassay ELISA technique to explore the role of CMV infection in
      inducing congenital anomalies. Six out of the 68 serum samples were found to be
      positive for CMV IgM. Four of them were detected among the congenital cases (5
      our to 55; 7.3%), while 2 cases were among the controls (2 out of 13; 15.4%). The
      microcephalic group showed 5.9% positivity (one out of 17). The jaundiced infants
      showed 14.3% positivity (3 out of 21), while all the cerebral palsy cases were
      negative for CMV IgM. Such a high percentage of CMV IgM in the control group may
      be attributed to asymptomatic infection, with liability for long term sequelae,
      particularly hearing loss or ocular abnormalities by 2 years of age. So,
      continuous follow-up of such asymptomatic cases is essential to control any
      possible congenital abnormality as early as possible.

PMID- 17214163
TI  - Infant mortality in rural Riyadh region of Saudi Arabia.
AB  - OBJECTIVE: The purpose of this study was to estimate the level of infant
      mortality in the rural area of Saudi Arabia central region. SETTING: Rural
      villages in the Riyadh area. DESIGN: A prospective study of a cohort of infants
      born in 1987 until they were one year old. METHODS: Five random villages were
      selected by simple random method. All the babies born in these villages were
      identified by a group of trained nurses. These nurses collected morbidity and
      mortality data on these children each time the events occurred using a structured
      data collection form. Data were analyzed using relevant demographic and
      statistical techniques. RESULTS: A total of 4,960 babies were born during the
      period of study. The neonatal mortality rate was 21.4 per 1000 live births and
      infant mortality rate was 53.8 per 1000. The post neonatal death rate was 32.5
      per 1000 live births. The causes of infant deaths as presumed from reported signs
      of last illness were gastroenteritis, respiratory problems, preterm birth
      complications and congenital abnormalities. CONCLUSION: There is a decline in
      infant mortality rate compared with previous estimated rates. But the high levels
      of neonatal death rates calls for improved antenatal and obstetric health
      services. The high post neonatal death rate indicates the potential for a further
      reduction.

PMID- 17214164
TI  - Development of smoking cessation program based upon opinions and suggestions of
      the smoker and non-smoker subjects.
AB  - This study aimed at investigating the opinions and suggestions of smokers and non
      smokers in order to develop smoking cessation program in Al-Madinah region.
      Representative random samples were selected from various sectors including
      governmental directorates, schools, hospitals and companies and other sectors.
      The study was conducted during 1995 (1415 H). Each subject was asked to complete
      a self administered questionnaire. The data were collected and analyzed by using
      the computer system. The results revealed that the majority of the participants
      favored the contributions of mass media, Ministry of Health and Ministry of
      Education in the anti-smoking program. However, the contributions of El-Emera,
      Policemen and Municipality were not accepted approaches by the majority of the
      subjects. Banning sale of cigarette, health education and forcible restriction of
      smoking at work places were suggested by most of the participants in order to
      restrict the smoking habit in Al-Madinah city.

PMID- 17214165
TI  - Risk factors related to deaf-mutism among pupils attending the Alexandria
      governmental deaf-mute schools.
AB  - Childhood deafness interferes with the cognitive development of the child, so it
      is considered a major handicap. The present work was carried out to reveal
      possible risk factors of deaf-mutism and the magnitude of each. The case control
      design was chosen as a research methodology. A 50% sample of deaf-mute pupils at
      the primary level were selected at random from each of the two governmental
      schools for the deaf-mutes in Alexandria (boys=96, & girls=76). A control group
      chosen at random from a main stream governmental school and matched by age and
      sex of the pupils as well as with education and occupation of the father.
      Matching was carried out at the sampling phase, pairing each case to its control.
      Data were collected by interviewing the mothers using an interviewing schedule.
      Matched analysis was carried out where pairing of cases and controls was
      retained. The likelihood estimate of Odds ratio conditional on the number of
      discordant pairs was estimated using McNemer's test. The 5% level was chosen as
      the level of significance. The study revealed 172 deaf-mute pupils. Their mean
      age was 9.48+/-1.981 years. Boys outnumbered girls (55.8% and 44.2%
      respectively). In 59.4% parents were cousins. Deafness was first noticed at 6 to
      60 months of age with a mean of 14.70+/-10.2 months. Most fathers and mothers
      were illiterate (48.84% and 61.63%). Heredity was a risk factor, where 84.82% of
      cases had a positive family history compared to none of the controls. Moreover,
      in case of consanguinity the Odds ratio=5.60. Acquired deafness constituted the
      second important group of all causes of deafness. Meningitis featured as the most
      important cause of acquired deafness with an estimated relative risk of 18.5,
      followed by fever (Odds ratio=4.67), then repeated attacks of acute tonsillitis
      and ear disease where the case control percent difference was 8.72% and 4.65%
      respectively.

PMID- 17214166
TI  - Study of the high prevalence of HCV in Egypt.
AB  - The correlation of schistosomiasis and other variables as a risk factor behind
      the remarkable high rates of HCV seropositivity in Egypt was studied by examining
      the sera of 188 subjects (94 apparently healthy villagers and 94 non professional
      blood donors) for schistosoma antibodies by Falcon assay screening test enzyme
      linked immunosorbent assay (FAST-ELISA) and for HCV antibodies by the application
      of screening (ELISA) and confirmatory (RIBA) techniques. The results showed that
      the overall prevalence of HCV antibodies was 29.8% by ELISA reduced to 21.8% i.e.
      73.2% confirmation by RIBA test. HCV-RNA (HCV viraemia) was detected in 76% of 25
      ELISA anti-HCV positive sera by P.C.R. technique. After adjustment for age, there
      was no statistical significant correlation between the remarkable high rates of
      HCV seropositivity in Egypt and risk factors studied other than blood
      transfusion, and schistosomiasis.

PMID- 17214167
TI  - Parasitic infections and gastrointestinal symptoms among preschool children in
      day care centers in Alexandria, Egypt.
AB  - There is a considerable amount of speculations concerning the presence of
      symptoms in various parasitic infections. The aim of the present study was to
      determine the prevalence of different parasitic infections among children in day
      care centers (DCCs), and to establish the relation of such infections to
      gastrointestinal symptoms. A total of 623 stool samples were collected from 700
      preschool children aged 2-5 years who attended 3 DCCs of different social classes
      in Alexandria. These samples were tested for parasitic infection by the
      conventional microscopy. Parents were interviewed as regards the gastrointestinal
      symptoms frequently suffered from by their children included in the sample during
      the 3 months period preceding the interview. The prevalence rate of parasitic
      infection was 56.0%. Giardiasis was the commonest infection (34.7%), followed by
      Ascariasis (24.4%) and Trichuriasis (4.6%). Boys showed a significantly higher
      prevalence than girls (58.3% vs. 52.9%, p<0.01). Social children were more
      infected with G. lamblia than unsocial ones (39.6% vs. 22.1%, p<0.01). Vomiting
      was strongly associated with G. lamblia infection (OR=7.1, p<0.01), diarrhea with
      multiple infections (OR=48.2, p<0.01), while abdominal pain was not significantly
      associated with any of these infections. The high prevalence of Giardiasis in
      DCCs emphasizes the need for increased surveillance for G. lamblia as a cause of
      vomiting in children, especially among active and social boys. Routine and
      periodic administration of a protozoan treatment to such children is recommended.

PMID- 17214168
TI  - Changes in serum lipid profile and esterases of rats after sublethal daily doses
      of dimethoate.
AB  - Male Wistar rats were injected by dimethoate (10 mg/0.5 ml) daily for 8
      successive days. Controls received the same amount of saline., A group of 5 rats
      were anesthetized at 0, 2, 4, 6 and 8 days of injection. Blood was withdrawn from
      heart. serum lipid components and 4 species of serum esterases were assayed for
      each group. A general decrease in the activities of serum esterases was observed.
      A marked decrease also was observed in lipids profile during the 8 days course of
      experiment.

PMID- 17214169
TI  - Relationship between smoking habit and sociodemographic factors.
AB  - The main purpose of conducting this study is to investigate the sociodemographic
      factors influencing the initiation of smoking habit in Al-Madinah city. A
      representative random sample was selected from different sectors in Al-Madinah
      region including government directorates employees, hospitals physicians, school
      students and others. Data were collected by a self administered questionnaire and
      analyzed by using the computer system. The results revealed that age, marital
      status, number of children and family smoking were significant influencing
      factors for initiating smoking habit, however, no significant relationships were
      found between smoking habit and education or monthly income. Our findings showed
      that about 80% of the smokers were cigarette smokers and 72% of them have tried
      to quit smoking but failed to do so, the reasons of failure were attributed to
      social and psychological stresses in 63% of cases. Our data also showed that
      friends and imitation of adults (51.2%) were the main reasons for initiating
      smoking habit.

PMID- 17214170
TI  - Prevalence of antibodies to hepatitis C virus in hemodialysis patients and renal
      transplant recipients.
AB  - This work was carried out to study the prevalence of hepatitis C virus (HCV)
      infection, its associated risk factors and possible routes of transmission in
      hemodialysis patients and renal transplant recipients. Ninety five patients and
      15 normal controls were included in this study. Patients were classified into 3
      groups: Group I (64 hemodialysis patients), Group II (16 renal transplant
      recipients) and Group III (15 patients with chronic renal insufficiency on
      conservative treatments). Each individual was subjected to full clinical
      examination, estimation of serum alanine aminotransferase (ALT), testing for
      antibodies to hepatitis C virus (anti-HCV), screening for hepatitis B surface
      antigen (HBsAg), antibodies to hepatitis B surface antigen (anti-HBs) and core
      antigen (anti-HBc) by modified ELISA technique. Anti-HCV was found in 87.5% of
      hemodialysis patients, 81.25% of renal transplant patients, 53.3% of the
      conservative group and in 13.3% of the control group. There was a significant
      correlation between the presence of anti-HCV and the duration on dialysis in
      groups I and II (p < 0.05), while no significant correlation was detected between
      HCV positive cases and the number of units of transfused blood in groups I and II
      (p > 0.05). Serum ALT was elevated in patients with HCV infection, but there was
      no significant correlation between the presence of anti-HCV and elevated ALT
      level among the examined groups of patients (p > 0.05). The prevalence of HCV
      infection was not correlated with the duration of renal transplantation and the
      type of immunosuppressive therapy (p > 0.05). Coinfection with HBV and HCV could
      occur, as previous infection with HBV was demonstrated. Anti-HBc was found in
      51.8%, 66.7%, 37.5% of anti-HCV positive patients in groups I, II, II
      respectively. Anti-HBs was detected in 24.1% and 15.4% of anti-HCV positive in
      groups I and II. HBsAg was found only in 4.7% of anti-HCV positive hemodialysis.

PMID- 17214171
TI  - Evaluation of BCG vaccination: an intervention study in Rail Region, Saudi
      Arabia.
AB  - Inspection of 300 infants attending a primary health care (PHC) center at Hail
      region showed that 18.8% of children failed to develop BCG reations. This
      directed attention to inspect the process of vaccination at hospitals in which
      80% of deliveries and BCG vaccination took place. Defects in the process of
      vaccination and cold chain system were noticed. Reorganization of the process of
      vaccination in addition to training the staff responsible for vaccination were
      done. A survey was followed to evaluate failure of BCG vaccination before and
      after the intervention. We checked 4145 infants two to twelve months of age, for
      any reaction at the site of BCG vaccination. After intervention vaccination
      failure dropped from 20.4% to 4.9% for infants vaccinated in hospitals (p =
      0.00001), and from 7.9% to 3.2% for those vaccinated in health centers (p =
      0.01). Moreover, before intervention success of BCG vaccination was significantly
      higher in PHC centers (92.1%) than in hospitals (79.6%). This difference became
      insignificant after intervention because success of BCG vaccination in hospitals
      has increased up to 95.1% compared to 96.8% in health centers. Inspection of all
      infants for BCG reaction is continued as a part of routine work at PHC centers,
      and re-vaccination of those who failed to develop reation to BCG is conducted
      without any reported complications.

PMID- 17214172
TI  - Study of different risk factor profiles in stroke patients in Alexandria.
AB  - The study included 94 stroke cases. They were admitted at the Internal Medicine
      Department between October 1994 and March 1995. For each case studied, an attempt
      was made to obtain, from the same hospital, age and sex matched control patient.
      The aims of this work are to identify different stroke risk factors and to
      measure the strength of association of the different risk factors and stroke.
      Results of this work revealed that hypertension, diabetes mellitus, ischemic
      heart diseases, arrythmias possible symptoms of transient ischemic attacks and
      android type of fat distribution are major risk factors of stroke in Alexandria.
      This necessitates initiation and continuation of stroke control program in
      Alexandria.

PMID- 17214173
TI  - The relationship between the knowledge of nursing staff and their compliance to
      universal precautions for prevention of hepatitis B viral infection.
AB  - This study examined the relationship between the knowledge of nurses working in
      Tanta Fever Hospital (N = 54) and their compliance to universal precautions as a
      prevention of HBV. An interview questionnaire and observation checklist were
      designed to fulfill the aim of the study. The study revealed that nurses'
      knowledge was below the average score in half of the items studied, while their
      performance was below the average in all the items except for care of
      contaminated instruments. Although no significant relation was found between
      nurses' knowledge and their performance regarding the universal precautions,
      nurses having less than 5 years of experience had a higher score of performance
      than those having more than 5 years of experience in 6 items. The study reflects
      the need for in-service educational and training programs on infection control
      for nurses.

PMID- 17214174
TI  - Human fascioliasis in an Egyptian village: prevalence and some epidemiological
      determinants.
AB  - A cross-sectional survey was conducted in Abis area, 15 kilometers south east of
      Alexandria city, to determine the prevalence of human fascioliasis and to study
      some of the epidemiological determinants which may affect the infection. A
      specially designed questionnaire interview was completed, and a total number of
      3475 stool samples were examined. The results revealed a prevalence rate of
      fascioliasis of 11% in the studied area which was only second to S. mansoni. The
      prevalence of infection was significantly higher among females in general and
      specifically in the age group 5 to less than 15 years and 25 to less than 35
      years. Family aggregation of fasciola infection was noticed among the studied
      group. The prevalence and also the risk of infection were significantly higher
      among children whose mothers were infected. They were, however, insignificantly
      higher among illiterate, single males, and low social class group. In addition,
      the prevalence and risk of infection were significantly higher among individuals
      obtaining their raw green leafy vegetables from multiple sources. From the
      results it was concluded that human fascioliasis is an important public health
      problem in Abis area with increased risk of spread of infection to Alexandria
      city through raw green leafy vegetables which represent the main source of
      infection.

PMID- 17214175
TI  - Maternal knowledge, attitudes, and practices as predictors of diarrboeal disease
      in Saudi children < 3 years of age.
AB  - Diarrhoeal disease continues to be a leading cause of morbidity and mortality in
      many developing countries. This study demonstrates the importance of behavioral
      risk factors as determinants of diarrhoeal disease. The study design used is
      incidence-base, case-control design. The cases were obtained from Primary Health
      Care Centers (PHCC) in Makkah area, Saudi Arabia, during October 1994 to January
      1995. The studied sample consisted of 319 cases and 312 controls < 3 years of
      age. The results showed that mothers of cases were significant inferior knowledge
      about aetiology and transmission of diarrhoeal disease than did mothers of
      controls. Poor hygiene was significantly high in households of cases for two
      items; disposal of faeces in latrine and presence of toilet papers (p < 0.05).
      Assuming causal association between the risk factors and diarrhoeal disease, up
      to 60% of diarrhoeal disease in the study population may be attributable to the
      studied behavioral factors.

PMID- 17214176
TI  - Controlled trial with human lymphoblastoid interferon among HBeAg and anti-HBe
      positive chronic hepatitis B patients in Egypt.
AB  - In a randomized controlled trial, sixty chronic hepatitis B liver disease
      patients (HBsAg +ve and HBV-DNA +ve) were randomly allocated into 2 groups. The
      first group comprised of 30 patients who were subdivided into 2 subgroups
      according to the HBeAg/anti-HBe system. One subgroup was HBeAg-positive (12
      patients) and the other was anti-HBe-positive (18 patients). All were given human
      lymphoblastoid IFN alpha (Wellferon-R) at a dosage of 5 MU, thrice weekly for 4
      months. The other 30 patients served as a control group, six of whom were lost
      during the study. The initial response was loss of HBV-DNA in 66.6% of the HBeAg
      +ve subgroup (8/12 patients), 33% in the anti-HBe subgroup (6/18 patients) and in
      8% in the control group (2/24 patients). Patients and controls were followed up
      for 8 months after the end of IFN therapy. A sustained response (loss of HBV-DNA)
      8 months after discontinuation of IFN was attained in 5/12 patients (41.6%) of
      the HBeAg-positive subgroup compared to none (0/24) in the control group (p <
      0.05). In the anti-HBe subgroup, a sustained response in 2/18 patients (11%)
      compared to none (0/24) in the controls was not significant. We conclude from
      this study that (Wellferon-R) at a dosage of 5 MU given thrice weekly for 4
      months was significantly better (p < 0.05) than no treatment in producing a
      sustained response among the HBeAg +ve subgroup of patients. On the other hand,
      in the anti-HBe subgroup the outcome of the previous schedule was not
      significantly better than in controls due to the small numbers involved although
      2 patients did have a sustained response.

PMID- 17214177
TI  - The prevalence of congenital malformations at birth in Ain Shams University
      Maternity Hospital Cairo, Egypt, 1994.
AB  - The prevalence of congenital malformations among births (live and still birth) at
      Ain-Shams Maternity Hospital was examined. Fifty five malformation cases were
      found among the whole births examined (1157 births) over the 9-month study
      period, this yields a prevalence rate of 4.75%, a rate similar to the worldwide
      prevalence rate. Elevated rate of neural tube defects was observed (13.8/1000)
      followed by limb deformities (12.1/1000). Case control study was also conducted
      to evaluate the different risk factors. The increased rate among cases can be
      explained by potential exposure at father employment, drug intake during
      pregnancy and history of fever using multivariant logistic analysis.

PMID- 17214178
TI  - Adolescent pregnancy: are there biological barriers for pregnancy outcomes?
AB  - The present prospective study comprised 111 adolescent (< 20 years) and 637 non
      adolescent (20+ years) pregnant women, at the main maternity hospital and 79
      primary health care centers in Taif area. Their demographic, behavioral,
      nutritional and socio economic data were analyzed with birth outcomes to compare
      the latter in the two study groups. The pregnancy outcomes considered were fetal
      growth retardation (small-for-date), low birth weight, and preterm delivery.
      Adolescent mothers were found to be more likely to deliver low birth weight
      infants even after controlling for major risk factors. The possibility of
      biological barriers to favorable outcome of pregnancy in adolescent mothers could
      not be overruled. However, more studies are needed to look at biological age
      rather than chronological age and to determine outcomes of pregnancy such as
      intra-uterine growth retardation and preterm delivery more accurately before
      drawing any conclusion.

PMID- 17214179
TI  - Bacteriological quality of ready to eat meals.
AB  - Microbial investigation of 30 samples of roasted liver and 30 samples of meat
      sandwiches, collected randomly from different peddlers and restaurants in
      Alexandria city, was conducted to evaluate their sanitary status. The average
      count/gm of total aerobic bacterial count thermophilic, total coliform and faecal
      coliform counts isolated from liver sandwiches were 8.11 x 10(6), 1.05 x 10(5)
      and 9.04 x 10(3), but from meat sandwiches (shawerma) were 7.06 x 10(4), 6.24 x
      10(3), 2.26 x 10(3) and 1.09 x 10(3) respectively. E. coli, Shigella, Staph.
      aureus could be isolated in varying percentages, but Salmonella failed to be
      isolated. The public health importance of the isolated microorganisms as well as
      suggested hygienic measures to improve the quality of such products are
      discussed.

PMID- 17214180
TI  - Surveying disabilities in Mafraq District in Jordan in view of approaching
      community based rehabilitation.
AB  - Disabilities in Mafraq District in Jordan were identified using active case
      detection. The identified disabilities were characterized by type, sex and age of
      the disabled as well as other variables pertaining to the reproductive history of
      their mothers and certain socioeconomic variables pertaining to their families.
      The results indicated an unmet need regarding services addressing the disabled
      and that they belong to poor families with high prevalence of illiteracy. The
      results also showed that the prevalence of consanguineous marriages as well as
      pregnancy at the two extremes of women's reproductive life is associated with
      congenital disability. The results were availed to the responsible authorities to
      facilitate embarking on Community Based Rehabilitation (CBR) in the district.

PMID- 17214181
TI  - Indoor air pollution and acute lower respiratory infections in the first two
      years of life.
AB  - The relationship between outdoor air pollution and acute respiratory infections
      (ARI) was previously documented. There are recent indications for connection
      between indoor air pollution and ARI in infants and young children. The aim of
      this study was to identify the relationship of indoor air pollutants to acute
      lower respiratory infection (ALRI) in children (< 2 years). The indoor air
      pollutants concentrations were measured in the homes of the sample. The sample
      consisted of 115 children (< 2 years) representing the control group (24), ALRI
      but no pneumonia (24), pneumonia (30), severe pneumonia or very severe disease
      (37). Air sampling was performed to measure the concentration of total suspended
      particulates (TSP), SO2 and CO. These pollutants were found in higher
      concentrations in cases' homes (52.46 +/- 19.68 microg/m3, 298.15 +/- 669.37
      microg/m3, and 1.92 +/- 3.60 ppm) than in controls' homes (31.92 +/- 8.76
      microg/m3, not detected, and 0.33 +/- 1.63 ppm respectively). Whereas SO2 was
      detected only in houses using kerosene, TSP and CO were detected with the
      different types of cooking fuels. Their mean concentrations were highest for
      biomass (88.86 +/- 13.30 microg/m3 and 9.29 +/- 2.50 ppm) and lowest for gas
      (40.78 +/- 15.25 microg/m3 and 0.76 +/- 2.19 ppm). Measures to improve indoor air
      quality are highly required.

PMID- 17214182
TI  - Comparative study on: morbidity and mortality among neonates of gestational and
      frank diabetic mothers.
AB  - The aim of this work was to study pregnancy outcome among gestational and frank
      diabetic mothers in comparison to non diabetic mothers. A case control study was
      done including all diabetic mothers who delivered in Ain Shams Maternity Hospital
      (ASMH) in 1992 plus an equal number of non diabetic mothers as a control group.
      Two hundred and three cases were delivered in ASMH during 1992; 132 of them were
      frank diabetics and 71 were gestational diabetics. It was found that there were
      no significant differences between neonates of gestational diabetic mothers
      (NGDM) and neonates of frank diabetic mothers (NFDM) regarding perinatal
      mortality rate, stillbirth rate, gestational age, mode of delivery and birth
      weight (p > 0.05). Meanwhile, there were significant differences between neonates
      of diabetic mothers and control group regarding all previous variables (p <
      0.01). Macrosomia was found in 42.3% of NGDM and 9.9% of NFDM (p < 0.001). Low
      birth weight was found in 12.7% of NGDM and 0.8% of NFDM (p < 0.001). Respiratory
      distress was significantly higher in NGDM (16.9%) than NFDM (6.8%) (p < 0.05).
      Regarding metabolic disorders and sepsis, there were no significant differences
      between NGDM and NFDM, while there were significant differences between total
      neonates of diabetic mothers and among the control group (p < 0.05). It was
      concluded that gestational diabetes is as important as frank diabetes and even
      has a more dangerous sequel. It is recommended to pay more attention to diagnosis
      and management of gestational diabetes.

PMID- 17214183
TI  - Do workers exposed to intermittent aircraft noise suffer from occupational
      deafness? A study in Alexandria airport.
AB  - The study aimed at assessment of noise levels in Alexandria airport and
      measurement of hearing acuity--among other health parameters of the working
      personnel. By performing 65 sound pressure level measurements, a questionnaire
      and air conduction audiometry, significant hearing defects could be revealed.
      Deficiencies affected hearing levels at all frequencies but especially higher
      frequencies in workers exposed to noise of aircrafts and other airport activities
      at the exterior of the airport building. The importance of pre-employment and
      periodic ear and audiometric examinations is thus expressed.

PMID- 17214184
TI  - Risk factors of psychosocial problems among children working in workshops in
      Alexandria.
AB  - This study was conducted to determine whether psychosocial problems occurring
      among working children are associated with other social or occupational factors.
      A sample of 34 working children ageing from 10-14 years was studied. They were
      classified into 2 groups according to the occurrence of psychosocial problems as
      anxiety, eating or sleeping problems, fatigue, nightmares etc... Interview data
      were examined to identify factors that might be considered as risk factors in
      psychosocial problems. Ten variables distinguished children with psychosocial
      problems. These variables were classified by the discriminant analysis technique,
      by order of importance as effort done, housing conditions, nature of the work,
      substance intake, educational status, degree of job satisfaction, income,
      nutrition, age and occupation. These variables correctly classified 100% of the
      affected group and misclassified 13.3% of the non affected group. This could
      alert health professionals to the existence of more pervasive disturbances in the
      child's labor conditions, as well as the child's environment.

PMID- 17214185
TI  - Maternal mortality in Mafraq District in Jordan.
AB  - The present study followed a multidimensional approach to determine maternal
      mortality ratio in Mafraq district in Jordan. It included active case (maternal
      deaths) surveillance combined with Civil Registry and hospital records review.
      Mafraq, by virtue of its geographic and demographic characteristics, is supposed
      to have a very high toll of maternal deaths and hence, generalizations reflecting
      the maximum expected maternal mortality ratio in Jordan could be made. The ratio,
      and as an average for the five years 1987-1991 covered in retrospect by the study
      was 42 deaths per 100,000 live births, very close to the estimated one.
      Establishing a baseline maternal mortality ratio and outlining risks pertaining
      to maternal survival as done in this study is an important prerequisite for
      interventions to reduce these risks and monitor progress towards reduction of
      maternal mortality ratio by half by the year 2000 which is a global goal to which
      Jordan is committed. The multidimensional approach followed by this study is
      shown to be superior to single source approaches in determining maternal
      mortality ratio in instances where populations are small and death registration
      is weak. The study suggests that maternal deaths (preferably as circumstances
      around the death and not as ICD coded, to avoid under reporting) should be
      reported in the same manner as notifiable diseases until improvements in death
      registration are completed and registries are accurate and valid.

PMID- 17214186
TI  - Evaluation of the effectiveness of dipstick haematuria and proteinuria in
      screening Schistosoma haematobium infection among school children in upper Egypt.
AB  - This study aimed at evaluation of validity and reliability of dipstick haematuria
      and proteinuria in screening school children for Schistosoma haematobium
      infection. It included a random sample of 400 school children aged 6-15 years in
      rural area of Fayoum Governorate, upper Egypt. Urine samples of the studied
      children were tested parasitologically by urine filtration technique as a
      reference test and semiquantitatively for haematuria and proteinuria using urine
      reagent strips as screening tests. Results of the study revealed that haematuria
      was a better indicator for Schistosoma haematobium infection than proteinuria, as
      it was more sensitive (85.5% 73.4%, respectively), specific (94.4% 82.9%,
      respectively) and reliable (kappa=92% 80%, respectively). Moreover, it had
      stronger relationship with intensity of infection (r=0.88 & 0.67, respectively).
      A combination of different grades of haematuria and proteinuria did not
      significantly increase either sensitivity or specificity. Dipstick haematuria
      could be a valuable technique in screening rural Egyptian school children who are
      at risk of urinary schistosmiasis.

PMID- 17214187
TI  - Epidemiology of anemia among attendants of primary health care, Jeddah.
AB  - This study was carried out to find the prevalence of anemia, as well as
      associated factors in the studied group. The material of this study included all
      reports of diseases that were sent from all PHC, Jeddah city, to the Health
      Information Systems Unit at the Directorate of PHC, Jeddah during the year of
      1415 Hegrian. Data about anemia were collected and analyzed. Results of the study
      showed that the prevalence of anemia was found to be 1.82% in the studied group,
      among Saudi population it was found to be 1.84%. The prevalence of anemia among
      females was found to be 2.39% which was significantly higher than that among
      males (1.25%). Also, the prevalence of anemia was found to be significantly
      higher among different age groups compared to those aged 1-4 years. The
      prevalence of anemia was found also to be affected by geographic distribution of
      the population.

PMID- 17214188
TI  - Educational program on self-management for asthmatic school children.
AB  - This study was conducted to improve asthmatic school children's knowledge, belief
      and behavior related to asthma in order to improve their control of the disease.
      A total of 54 school children suffering from moderate or severe asthma who are
      attending the allergy center affiliated to school Students' Hospital of
      Alexandria were enrolled in the present study. An educational intervention was
      provided to these asthmatic children, each one was accompanied by one of his/her
      parents. It consisted of two components: classes conducted in group settings and
      individualized monthly visits. The intervention continued for a 6-month period.
      An interview questionnaire was used to assess both children's and parent's
      knowledge and beliefs related to asthma before and after the intervention. The
      children's inhaler use technique was also assessed twice by an observational
      check list. The study revealed significant improvement in both children's and
      parent's knowledge and beliefs concerning asthma inhaler use technique which
      significantly improved and positive behavioral changes were reported. The
      frequency of emergency room visits (ERV) due to asthma over a 6-month period
      after the initial assessment was substantially less than in the prior 6-month
      period (p<0.05). It could be concluded that patient education can significantly
      affect asthmatic's knowledge and behavior and consequently morbidity as revealed
      by reduction of frequency of ERV. It should be considered one of the major
      components of asthma care.

PMID- 17214189
TI  - Inheritance of non-syndromal genetic deafness.
AB  - This study was carried out on 35 patients with undifferentiated genetic hearing
      loss attending the Human Genetics Clinic, Medical Research Institute, Alexandria
      University. Their ages ranged from three months to 25.5 years. Females were
      commonly affected than males. The high parental consanguinity (75%) with high
      inbreeding coefficient (0.04) declared the role played by consanguinity, which is
      an important risk factor, in the occurrence of the abnormality. The type of
      hearing loss in all patients is sensorineural. The diagnosis of deaf patients was
      done by means of pedigree analysis and audiometric criteria. They were classified
      according to their diagnosis into four cases with dominant inheritance, 21 cases
      having congenital deafness showed recessive inheritance with a recurrence risk of
      0.277+/-(1.96) (0.10), one case with childhood deafness also showed recessive
      inheritance and one case with X-linked inheritance. Six cases were isolated
      cases, their mode of inheritance was indefinite except one case which may have
      suggested dominant inheritance. Two cases of ototoxicity in childhood also
      suggesting genetic causes were included. Genetic counselling was offered to the
      deaf parents to help the family to accept and adjust to the birth of a deaf
      child. The nature of the condition, prognosis and recurrence risk were explained
      to the parents.

PMID- 17214190
TI  - Association of parasites and diarrhoea among children less than five years of age
      in a rural area in Egypt.
AB  - A case control study was conducted in Kafr El-Sheikh Governorate, Egypt, a rural
      community, to assess the relation of parasites and diarrhoea among children <5
      years. A sample of 196 cases with diarrhoea and 83 non-diarrhoeic controls were
      included in the study. A questionnaire was completed for every child and weight
      and height were recorded. A stool sample was obtained and examined for parasites
      present. The results revealed that 70.3% of cases had parasites compared to 59%
      of controls. The most common parasites found were Entamoeba histolytica,
      cryptosporidium, and Giardia lamblia consecutively. In both groups the percent
      positive parasitic infection increased with age. The different socioeconomic and
      sanitary indicators studied were similar among both groups and could not explain
      the diarrhoea present except for the significantly higher presence of piped water
      inside houses of controls. Study of malnutrition revealed that a significantly
      higher percentage were stunted (15.6%) among cases than among controls (6.5%) and
      13.8% were wasted among cases compared to only 2% among controls. Undernourished
      cases were 14.8% compared to 4.3% of controls.

PMID- 17214191
TI  - Effect of occupational exposure to ammonia on enzymatic activities of catalase
      and mono amine oxidase.
AB  - The study was carried out to investigate the effect of ammonia inhalation on a
      total number of 60 male subjects from an urea production plant located in
      Alexandria. Laboratory investigations were carried out for 30 exposed and 30
      controlled subjects. The results showed statistically significant inhibition
      (p<0.01) in the activity of catalase enzyme among the exposed than the control
      subjects. The inhibition could lead to deleterious effects on electrical
      stability, permeability and fluidity of membranes, which could affect the liver
      and brain to be more susceptible to hepatotoxic and neurotoxic alterations. The
      present work showed a significant inhibition (p<0.01) of monoamine oxidase (MAO)
      activities and significant increase (p<0.05, 0.01) in liver function activities
      among exposed subjects than the control subjects.

PMID- 17214192
TI  - Environmental stress and genetic damage in aquatic organisms.
AB  - This work was planned to investigate the effect of pollution upon the genetic
      material of aquatic organisms. In order to achieve such a purpose, Tilapia
      nilotica and Tilapia zillii were chosen and caught from two regions varying in
      their environmental stress; the first is River Nile and the second is a closed
      drain which receives domestic sewage. Mitotic activity, chromosomal aberrations
      and in vivo induction of sister chromatid exchanges were examined in gills as
      well as in kidneys. The results obtained revealed that the environmental stress
      was proven to be capable of causing inhibition of cell proliferation; clastogenic
      effect and primary DNA damage in gills and kidneys of both species with
      differential effect.

PMID- 17214193
TI  - Newborn screening for certain treatable inborn errors of metabolism in
      Alexandria.
AB  - The study was conducted on two groups of newborn infants: Group A; a random
      sample of 3000 infants attending different Health offices in Alexandria for BCG
      vaccination. Their ages ranged from 5-120 days with a mean age of 39.9 days.
      Group B; included all the infants born to high risk families attending the clinic
      of Human Genetics Department, Medical Research Institute (9 infants; 7 with
      family history of PKU and 2 with family history of congenital hypothyroidism).
      Their ages ranged from 7 to 60 days with a mean age of 18 days. The newborn
      infants of the two groups were screened for three treatable inborn errors of
      metabolism, phenylketonuria "PKU", galactosemia and congenital hypothyroidism
      with the aim of early detection and therapy to prevent mental retardation. In
      group A; one baby with transient hyperphenylalaninemia (HPA) (0.33%) and one
      presumptive case of galactosemia (0.33%) were found. Initial positive results
      were found in eleven infants they had high levels of thyroid stimulating hormone
      (TSH). On reevaluation of nine infants of them they were all euthyroids. In Group
      B, four infants were detected among the infants of PKU families. After
      confirmation of these results breast feeding was stopped at once and the infants
      started their dietary management and were kept on it with follow up and periodic
      evaluation of the adequacy of treatment.

PMID- 17214194
TI  - Study of aluminium and lead in some traditional Omani dishes.
AB  - Because of the recent interest on the aluminium content of foods cooked in
      aluminium saucepans and the association between aluminium and lead and many toxic
      symptoms and disease, information about the source of exposure of man to these
      metals specially from food and drinks are required. Thirty four of the most
      commonly consumed Omani dishes were analyzed for their aluminium and lead
      content, in order to determine the level of contamination and to estimate the
      approximate oral intake of each metal. The level of aluminium in the studied
      dishes was in the range between 0.98 and 16.53 mg/kg with a mean 5.4 mg/kg. The
      highest level of aluminium was found in fish dishes (9.03 mg/kg) and meat and
      poultry dishes (7.66 mg/kg). The effect of using aluminium pans on the metal
      level was also studied in some foods. The effect varies from slight increase in
      case of frying or cooking of fish to a significant increase in case of baking
      rakal bread on aluminium flat pan. The level of lead in the studied dishes ranged
      between 0.026 and 1.75 mg/kg with a mean of 0.32 mg/kg. Salted fish contained the
      highest level of lead (0.57 mg/kg). The approximate daily intake, calculated on
      the base of the serving quantities, was found to be within the acceptable daily
      or weekly intake recommended for each metal.

PMID- 17214195
TI  - Comparative study between paratyphoid A and typhoid fever cases.
AB  - Twenty eight positive blood culture paratyphoid A fever cases were studied. Forty
      two positive blood culture typhoid cases were taken as controls. Cases and
      controls were subjected to: 1) careful history, 2) thorough clinical examination,
      3) two blood cultures for salmonella, 4) Widal agglutination test, 5) total and
      differential white blood count, 6) urine and stool cultures following therapy.
      There was no significant difference in the clinical picture between acute
      paratyphoid A fever and acute typhoid fever except the significant decrease of
      anorexia (57%), toxic look (54%), coated tongue (64%) in acute paratyphoid A
      cases when compared to acute typhoid cases. The prevalence of extraintestinal
      symptoms in paratyphoid A cases may mimic viral infections. Three of the 4
      classical signs namely; toxic look (54%), bronchitic chest (50%), splenomegaly
      (72%) and tympanitis (64%) were good bed side suggestive clinical diagnostic aids
      in paratyphoid A cases. Blood culture was the cornerstone of diagnosis of
      paratyphoid A cases. In 6 (21%), only the second blood sample was positive
      stressing the value of multiple cultures. Significant Widal antibody titre was
      elicited in only about half (57%) of paratyphoid A cases which was significantly
      lower than typhoid cases (83%). Leucopenia was found in only 25% of paratyphoid A
      cases. Eosinopenia was constant and is considered as a diagnostic and prognostic
      aid. No correlation was elicited between either the height of antibody titre or
      the height of leucocytic count and the severity of illness. There was no
      significant difference in the response to therapy or the occurrence of
      complications between paratyphoid A cases and typhoid cases. Up to the current
      knowledge, this is the first report on comparative study between acute
      paratyphoid A fever and acute typhoid fever in Egypt from clinical, diagnostic,
      therapeutic and prognostic points of view.

PMID- 17214197
TI  - Ocular disorders among workers exposed to mercury.
AB  - Mercury vapor exposed workers may show ocular changes, as well as other systems
      affection. A sample of 84 workers in preparing mercury fulminate were examined
      for conjunctival corneal and lenticular manifestation of long duration exposure,
      together with mercury urinary output. Lens changes were found in 50% of the
      involved workers while keratopathy as recorded in 34.5% of them. No statistically
      significant association was found between the occurrence of eye lesions and
      levels of urinary elimination of mercury. These results suggest local absorption
      of this element is most probably the underlying cause of ocular affection.

PMID- 17214196
TI  - Prevalence of certain sexually transmitted diseases in Egypt.
AB  - The prevalence of STD continues to increase throughout the world threatening
      millions of people. However, the actual incidence of STD is not known in most
      countries. Little work was done to evaluate the size of this problem in Egypt.
      This study aimed to identify the most prevalent sexually transmitted organisms
      among patients attending the STD clinic at Cairo Hospital for Skin and Venereal
      Diseases (El-Haud El-Marsoud). Among the patients attending this clinic
      complaining of one or more STD or not complaining, but attending the clinic for
      screening for fear from STD due to their sex behavior, from October 1993, to
      April 1995, 95 cases were studied. This was done by history taking, clinical,
      bacteriological and Certain demographic and interacting with sexual serological
      examinations. socioeconomic factors attitudes and practices were also studied.
      Data were recorded in special sheets. The results of this study showed that 68
      (71.6%) patients had one or more ST organisms (positive cases) while no ST
      organisms could be detected in the remaining 27 (28.4%) cases (negative cases).
      Positive cases were more prevalent n adolescents and young adults (58.8%). A high
      prevalence of STD was detected in males (73.5%) than females (26.5%); in sinlges
      (64.7%) than married (30.9%), divorced (2.9%) or widowed (1.5%). The rate of the
      positive cases was high among those having 5 or more sexual partners and in
      heterosexuals. All STD positive patients were not condom users except one
      patient. Most of patients were not drug abusers (66.2%) and were of low
      socioeconomic class (85.3%). STD were common among those with preparatory school
      education level (32.4%), or illiterate (26.5%) than those with primary school
      level (16.2%) or university or institute degree (13.2%) or secondary school
      degree (11.8%) of education. Among the 68 positive cases, N. gonorrhoeae was
      isolated from 36.8%, T. pallidum was detected in 30.9%. Using the appropriate
      serological techniques, HBV and HIV were detected in 14.7% and HCV in 11.8%. G.
      vaginalis was isolated from 11.8%; each of group B Streptococci and Strept.
      pneumoniae was isolated from 4.4% and each of T. vaginalis and C. albicans was
      isolated from 1.5%. Concomitant STD were detected in 18 out of 68 patients. So,
      STD is a variable state regarding the number of the causative organisms and their
      relative incidence according to several factors. For that, the state of STD in
      any location must be checked periodically to plan restrictive managing and
      controlling programs.

PMID- 17214198
TI  - A study of maternal and child health care services and private sector in urban
      Asir Region.
AB  - The differences in the maternal and child health care services offered by
      government and private sector in Abha and Khamis Mushayt cities in Asir Region of
      Saudi Arabia were compared. Self administered questionnaires and observation
      sheet were used for the study. It was found that the government clinics were more
      involved in the running of under 5 clinics and giving health education to
      patients. The private clinics took more care of women general health care but
      lacked the continuous domiciliary visit to pregnant women. The catchment area
      which served the government PHCCs made accessibility to service easier to
      government patients and this was thought to be the reason why government patients
      kept regular appointments. On the other hand, private patients who have the
      freedom to choose where they get service have been found to be irregular in
      keeping clinic appointment. It was suggested that there should be geographical
      spread in the location of private clinics to facilitate accessibility and that
      the health education and under 5 clinics should be well incorporated into the
      services offered by private clinics.

PMID- 17214199
TI  - The impact of health education on the knowledge and attitude of Egyptian nurses
      towards occupational HIV infection.
AB  - There is a phobia about nursing human immunodeficiency virus (HIV) infected
      patients. This work was carried out to study the impact of health education on
      the knowledge and attitude of nurses, representing a stratum of health care team,
      about modes of transmission and prevention of occupational HIV infection. The
      studied population were students of the High Institute of Nursing, they were
      subjected to a health education program (HE), and assessment was carried out
      before and after this intervention. The results revealed that health education is
      a successful tool in improving the knowledge of the nurses and in minimizing
      their phobia from occupational HIV infection.

PMID- 17214200
TI  - Comparative study between different diagnostic techniques in huge splenomegaly
      cases in El-Minia Province.
AB  - Fifty four patients presenting by huge splenomegaly were admitted to Tropical
      Medicine Department, El-Minia University Hospital. Tissue biopsy revealed pure
      bilharziasis due to S. hematobium in 10 (19%) cases, liver cirrhosis in 23 (42%),
      mixed schistosomiasis and cirrhosis in 8 (15%), hepatoma in 3 (6%), lymphoma in 6
      (11%) and hematological diseases in the form of chronic myeloid leukemia in 2
      (3.5%) and thalassemia major in 2 (3.5%) cases. The sensitivity and specificity
      of abdominal ultrasonography was 100% and 97% in cases of schistosomiasis, 100%
      and 100% in cases of hepatoma, 87% and 100% in cases of liver cirrhosis, 33% and
      100% in cases of lymphoma respectively. There was a positive significant
      correlation between endoscopic variceal grading, portal vein diameter, splenic
      vein diameter, size of the spleen and the grading of the portal tract
      thickenings. The pathological and ultrasonographic diagnosis was the same in 38
      (70%) cases. Splenogram was characteristic but not diagnostic in cases of
      schistosomiasis and liver cirrhosis. It was diagnostic and similar to peripheral
      blood picture in the 2 cases of chronic myeloid leukemia and was normal in cases
      of thalassemia major. Splenic aspiration was able to diagnose all cases of
      lymphomas. It can be considered as a useful adjunct to the usual diagnostic
      procedures, both in staging and follow up, especially in cases presenting only by
      splenomegaly.

PMID- 17214201
TI  - Evaluation of expanded program on immunization during the first year of life in
      Abu Dhabi.
AB  - This study was intended to highlight the program of vaccination in the first year
      of life against the Expanded Program on Immunization (EPI)-target diseases and to
      determine the trend of these diseases in Abu Dhabi during 1984-1989. The data
      were collected from annual reports of Ministry of Health. This retrospective
      study pointed out to the following results: (1) The average vaccination coverage
      (percent) during the first year of life against EPI-Target diseases increased
      gradually during 1984, 1986, 1987, 1988, 1989. (2) The vaccination coverage
      (percent) during the first year of life using BCG and measles vaccines are
      increased significantly (p < 0.001) during 1985-1989 compared with 1984. (3) The
      vaccination coverage (percent) during the first year of life using OPV and DPT at
      the third dose are increased significantly (p < 0.05) during 1987-1989 compared
      with 1984. (4) The reported cases of measles and its incidence rate consequently
      decreased during 1988-1989 compared with 1987 and the differences are
      statistically significant (p < 0.001). The reported cases of diphtheria and its
      incidence rate show significant increase (p < 0.01) during 1988 compared with
      1984. Other EPI target diseases do not show any statistically significant
      difference (p > 0.05) during 1985-1989 compared with 1984. Based on this study it
      can be concluded that with increase in average vaccination coverage (percent)
      from 58.5% in 1984 to 82.9% in 1989, the number of reported cases of EPI target
      diseases decreased.

PMID- 17214202
TI  - Lipids and fatty acids composition in Bolti (Tilapia nilotica) fish flesh as
      affected by environment.
AB  - Bolti (Tilapia nilotica) fish and water samples were taken from three different
      locations in Kafr El-Sheikh governorate. Water quality and oil characteristics in
      fish flesh were studied. The obtained results showed that crude lipid and
      phospholipid contents of fish fillet were increased by increasing total solids
      and total hardness of fish environment. Peroxide, iodine and acid values of fish
      oil influenced by water quality. Fatty acids composition in fish oil showed a
      wide variation due to differences in water-head. Total unsaturated fatty acids in
      drainage fish oil were higher than that found in farm's fish oil, while the
      lowest percentage of unsaturated fatty acids was recorded by Nile's fish oil.
      Generally, palmitic was the main saturated fatty acid in fish oil, whereas it
      constituted about 66-68% of the total saturated fatty acids. Nile's fish oil
      contained higher amounts of omega-3 fatty acids than those of drainage and farm's
      fish oils. In contrast, odd and branched fatty acids content in drainage and
      farm's fish oils were higher than those found in Nile's fish oil. Concentrations
      of arachidonic and erucic acids in oil extracted from drainage fish were higher
      than oil extracted from farm's fish, while the lowest concentration for these
      fatty acids were found in oil extracted from Nile's fish. Although the acid value
      and peroxide value of drainage and farm's fish oils were slightly high, it is
      still accepted for human consumption according to The Association of Fish Meal
      Manufacturers.

PMID- 17214203
TI  - Microbiological investigation and nutritional evaluation of selected fast food
      meat.
AB  - The study was designed into two parts: the first part was to determine individual
      attitudes and beliefs toward fast food in general. One hundred individuals (15-45
      yrs old) were involved in this study (50 males and 50 females). The second part
      of the study was carried out to evaluate microbiological contamination and
      nutritive value of the selected fast food meat (Hardee's fried burger, Saudi
      American burger, kentucky fried chicken, Al-Baik broast chicken and shawerma
      beef). The results indicated that individuals 25-45 yrs. old were the most fast
      food consumers. The main reason behind increasing individual's preferences toward
      fast food was found to be for fun and inspiration. Among individuals under study
      46% of males and 20% of females purchased fast food more than 4 times per week.
      Prevalence of overweight and obesity respectively were 38% and 22% among males
      and 34% and 14% among females. Bacillus cereus and E. coli were detected in a
      number of less than 10/g in all the selected fast food meat. The number of
      coliforms detected in Hardee's burger and Saudi-American burger were 10/g, while
      less than 10/g were detected in the remaining fast food meat. However, the number
      of Staph. aureus detected in Hardee's burger and Saudi-American burger was 20/g
      and 10/g respectively. On a per 100 g basis, energy (Kcal), protein (g), fat (g)
      and sodium (mg) content were found in the range of 179.62-295.29, 13.05-26.06,
      8.9-21.13 and 640-920 respectively. Sodium content of all the selected fast food
      meat exceeded the recommended daily adequate intake for adults (males and
      females). The observations of the present study indicated the need for a
      nutrition education program to correct consumers' attitudes and beliefs towards
      fast food and to provide information on how a given menu item contributes to
      their dietary goal.

PMID- 17214205
TI  - Effects of industrial formulations of Bacillus thuringiensis on the biology of
      Musca domestica L. (Diptera : Muscidae).
AB  - The effects of two industrial formulations of Bacillus thuringiensis (Bactimos
      and Vectobac) on larval and adult stages of Musca domestica L. were assessed in
      the laboratory. Biocides concentrations of 0.4% to 2% were tested on larvae,
      while the concentrations of 1% and 2% were tested on adults and were given to the
      flies in their diet. Larval mortality ranged between 38% and 53% and between 55%
      and 71% for bactimos and Vectobac respectively. Pupation rates decreased from 91%
      in the control group down to 47% and 29% for Bactimos and Vectobac respectively.
      Moreover, adult emergence rates decreased 3-4 folds in groups treated with the
      highest biocide concentrations. The effect on adult mortality was relatively
      lower, as control adults showed 4% mortality whereas those treated with Bactimos
      and Vectobac experienced 17-28% and 32-44% mortality respectively. In addition,
      biocides treatment induced a dramatic decrease in female fecundity from 273
      eggs/female in the control to 118-180 eggs/female treated siblings. These
      findings indicate that Bactimos and Vectobac possess both direct and indirect
      harmful effects on Musca domestica.

PMID- 17214204
TI  - Intravenous drug addicts: a high risk group for infection with human
      immunodeficiency virus, hepatitis viruses, cytomegalo virus and bacterial
      infections in Alexandria Egypt.
AB  - In this work the seroprevalence of HIV, HBV, HCV and CMV were studied among two
      groups of population; IVDA (intravenous drug addicts) (100) and control group
      (40). Syphilis and other bacterial infections which may be encountered among IVDA
      were also investigated. It was found that all serum samples (of both groups) were
      negative for anti-HIV. Regarding HBV markers, the prevalence of HBc antibodies
      was significantly higher among IVDA (62%) than the control group (27.5%). Also
      HBsAg was detected in 16% of IVDA while it was 75% among the control group.
      Prevalence of anti-HCV was significantly higher among IVDA (63%) than the control
      group (27.5%). The prevalence of co-infection with HBV and HCV was significantly
      higher in IVDA (40%) than the control group (15%). Sharing of needles and
      duration of drug use were positively associated with the presence of both HBV
      markers and anti-HCV. CMV seroprevalence was high in both groups. Antibodies to
      Syphilis were found in sera of 3 IVDA and one control using MHA-TP test. Although
      HIV infection has not yet been sufficiently introduced among IVDA in Alexandria
      but potentials for its spread among addicts are high as supported by observation
      that other infections with similar mode of transmission are common among addicts.

PMID- 17214206
TI  - Sociodynamic profile of the elderly living in geriatric institutes in Alexandria.
AB  - Living in geriatric institutes is not the optimum for the elderly. But under
      certain circumstances there will be no safe home for the elderly to live in. So
      they resort to living inside such institutes. The present study showed that the
      majority of residents at Dar Al Saada and Dar Al Hanaa were missing outside care
      giver. They showed economic dependency with a higher rate among females. Also,
      they did not have good original relation with their offsprings. Most of the group
      were physically dependent. They restricted their outside movement after
      admission. The sociodynamic interaction inside the institute was found to be
      good. It was a compensation for lost companionship and enjoying shared life.

PMID- 17214207
TI  - Knowledge of primary school teachers in Alexandria about asthma.
AB  - This study was conducted to elucidate the level of knowledge about asthma among
      primary school teachers in Alexandria. An interview questionnaire was constructed
      to collect data from 318 teachers chosen through a multistage stratified random
      method from 10 primary schools in Alexandria. The questionnaire included personal
      data and a series of statements about asthma that were to be answered. The study
      revealed that the teachers had limited knowledge about asthma in children. Most
      of them believed of the importance of playing sports for the asthmatic children.
      About 11% of the teachers did not permit an asthmatic child to keep his medicine
      with him during school hours. A significant difference in the level of knowledge
      about asthma was found between teachers who had received instructions and those
      who did not. It is recommended that instructions about asthma should be given to
      all primary school teachers during their teacher training courses.

PMID- 17214208
TI  - Hemophilus influenzae and Streptococcus pneumoniae as causative agents of
      pneumonia in Egyptian preschool children: analysis and serotyping of Hemophilus
      isolates from hospital patients in Cairo, 1991-93.
AB  - The Hemophilus influenzae blood culture and nasopharyngeal isolates, collected
      during a limited Surveillance of Antimicrobial Resistance in 1991-1993 from 1,635
      Egyptian children under 5 years of age, presenting with pneumonia to Embaba and
      Abbassia Fever Hospitals, were serotyped. The 8 blood culture isolates confirmed
      H. influenzae to be responsible for 0.5% of the cases of pneumonia, versus 50
      Streptococcus pneumoniae blood culture isolates from the same population that
      confirmed it responsible for 3.1% of the cases. The invasive Hemophilus strains
      were exclusively isolated from infants below 1 year, from one hospital (Embaba),
      on one winter season (January to March, 1992). On serotyping, 50% of the blood
      culture isolates were found to be non-b by latex agglutination. Some 297
      nasopharyngeal isolates from cases of pneumonia were also serotyped and 45% were
      found to be non-b, thus confirming the invasive strains findings. Furthermore,
      the typing results from ARI-free controls nasopharyngeal isolates--though limited
      -were consistent with the findings and showed a 43% proportion of non-b. These
      findings put a question mark on the benefit of a large scale use of the available
      H. influenzae type b polysaccharide and conjugated vaccines in Egypt. But before
      interpreting out data in terms of vaccine needs, more specifically designed
      epidemiological studies need to be conducted to assess the role of H. influenzae
      as a pathogen in Egypt.

PMID- 17214209
TI  - Iron deficiency anemia in Dubai Medical College for Girls: a preliminary study.
AB  - Iron deficiency anemia is still one of the major public health problems all over
      the world. Particularly in developing countries the complete ecological picture
      is not well established. All students in the first and second academic years of
      Dubai Medical College for Girls were included in the present study. The mean Hb
      was 12.83 +/- 1.49 and that for serum iron was 13.73 micromol/L +/- 4.79. Anemia
      was detected among 24.62% of the group among which Arab Gulf Nationalities
      constituted 31.25%. Egyptians showed the highest prevalence of anemia (50%). The
      study showed a significant effect of chronic blood loss whether menstrual or from
      any other cause upon the Hb level. Also living in the hostel away from parents
      and families was reflected upon their diet habits and had a significant
      reflection upon the prevalence of anemia among the studied group.

PMID- 17214211
TI  - Cloning goes to the movies.
AB  - Public attitude research conducted by Biotechnology Australia shows that one of
      the major sources of information on human reproductive cloning is movies.
      Traditionally, understanding of new and emerging technologies has come through
      the mass media but human cloning, being so widely addressed through the popular
      culture of movies, is more effectively defined by Hollywood than the news media
      or science media. But how well are the science and social issues of cloning
      portrayed in box office hits such as The Island, Multiplicity, Star Wars: Attack
      of the Clones and Jurassic Park? These movies have enormous reach and undoubted
      influence, and are therefore worth analyzing in some detail. This study looks at
      33 movies made between 1971 and 2005 that address human reproductive cloning, and
      it categorizes the films based on their genre and potential influence. Yet rather
      than simply rating the quality of the science portrayed, the study compares the
      key messages in these movies with public attitudes towards cloning, to examine
      the correlations.

PMID- 17214210
TI  - [The transparent body: medical imaging and popular culture in the twentieth
      century].
AB  - In today's societies, successful new medical imaging technologies have focused
      unprecedented attention on the inside of the human body. These techniques have
      jumped the walls of the biomedical field per se, penetrating the fields of
      culture and law. The article traces a genealogy of twentieth-century medical
      techniques used to visualize the human body and brain, from X-rays to the more
      sophisticated CTs, MRIs, and PET scans. It explores the changes that these ever
      more numerous visualization techniques have occasioned in our corporality and
      examines how these technologies have been received in the courtroom and in
      popular culture, especially in literature, movies, and magazines.

PMID- 17214213
TI  - Dentists treating sleep apnea.

PMID- 17214212
TI  - What's old is new again.

PMID- 17214214
TI  - The effect of 16 percent carbamide peroxide on enamel staining susceptibility.
AB  - STATEMENT OF PROBLEM: Recently, vital bleaching by carbamide peroxide has become
      more popular; therefore, it is necessary to study the effect of this agent on
      enamel and dentin. PURPOSE: The purpose of this study was to evaluate the effect
      of a 16 percent carbamide peroxide bleaching gel, Vivastyle, on enamel staining
      susceptibility. MATERIALS AND METHODS: Thirty bovine specimens were selected and
      randomly divided into two groups of 15. The experimental group was subjected to
      Vivastyle gel and then was immersed in coffee for half an hour daily for three
      weeks. The control group was only immersed in coffee. The teeth were evaluated
      using a colorimeter to measure L*, a*, b* of each tooth. Value (black to white)
      is denoted as L*, wheres chroma (a* b*) is denoted as red (+a*), green (_a*),
      yellow (+b*), and blue (_b*). Total color differences between two colors (deltaE)
      were calculated using the following formula: deltaE = [(deltaL*)2 +
      (deltaa*)2+(deltab*)2]: deltaE1.Bleached, AE2: bleached and immersed in coffee,
      deltaE3: immersed in coffee. RESULTS: Mean differences were: deltaE1 = 9.478,
      deltaE2 = 13.808 and deltaE3 = 7.230. Paired comparison by use of Duncan test
      showed there was a significant difference between deltaE1 and deltaE2 (P0.000);
      and t test showed there was no significant difference between deltaE3 and
      deltaE1. (P0.08 > 0.05), but deltaE3 showed a significant difference with
      deltaE2(P0.000). CONCLUSION: After vital bleaching, the enamel staining
      susceptibility significantly increased.

PMID- 17214215
TI  - Evidence-based research in alternative protocols to dental implantology: a closer
      look at publication bias.
AB  - Several techniques exist for the surgical placement of dental implants. The aim
      of this study was to assess systematically, the efficacy of these protocols by
      the evidence-based perspective. Five best-case studies involving 607
      early/immediately loaded implants and 300 conventionally loaded implants were
      identified by examining the available literature and rigorous inclusion/exclusion
      criteria. Overall analyses demonstrated a 98.4 percent success rate for the
      early/immediate procedure and a 95.3 percent for the conventional protocol.
      Success rates in the articles reviewed were based on implant survival over a
      follow-up period of between one to two years. A meta-analysis was generated to
      evaluate the presented evidence and to aid in decision-making. Despite its common
      implementation, this technique presents many caveats, among which publication
      bias is one of the most common. To investigate the possible presence of
      publication bias, a funnel plot analysis complemented several statistical tests.
      By means of the systematic investigation of dental implants, the authors' results
      confirm the presence of publication bias in implant dentistry literature, which
      strongly suggests that clinicians ought not base their decisions solely on the
      results presented by a few published studies. Rather, it is recommended that
      clinicians cautiously draw conclusions and seek studies that present accountable
      and clinically relevant results. Furthermore, it is suggested that clinicians
      attend seminars to learn of the effective advances in evidence-based dentistry,
      so as to develop the ability to easily detect inadequate literature due to
      attempted correlation with the most current research. It is also recommended that
      additional research is necessary to analyze which fields of research are more
      prone to bias, thus forewarning clinicians before formulating clinical
      conclusions.

PMID- 17214216
TI  - The economics of dental practice--present and future.
AB  - The combination of increased practitioner income, increases in the proportion of
      the population reporting visits for dental services, decreases in the number of
      dental school graduates, decreases in the dentist-to-population ratio, and
      increases in the number of female students and practitioners (many of whom report
      significantly fewer work hours than their male counterparts), portends favorable
      economics for dental practices. However, the cost of dental care is "felt" to a
      greater extent than for other health services. Current and future funding
      arrangements for dental services could be vulnerable to economic downturns,
      efforts to control business overhead costs and continued minimal government
      support. There may need to be concern regarding the infrastructure of economics
      of dental practice. A series of favorable developments, including increasing
      dental practitioner income, an increasing use of dental services, decreasing
      numbers of graduates and decreasing practitioner-to-population ratios would seem
      to favor continued encouraging prospects for the future of dental practices.
      However, compared to other health services, the reliance on (1) out-of-pocket
      funding for a major share of dental expenditures, and (2) limited government
      support for dental services raise questions regarding the infrastructure of
      dental economics. These subjects are reviewed in the following presentation.

PMID- 17214217
TI  - The use of autogenous bone grafting with platelet-rich plasma for alveolar ridge
      reconstruction: a clinical report.
AB  - Implant dentistry has become an effective and predictable treatment modality in
      modern dentistry. Patients with missing teeth can benefit from partial or
      complete tooth replacement. Implants can also be used to improve denture
      retention, stability and support, and enable improved function and esthetics for
      patients. Several implant systems are commercially available, and their use is
      predictable with excellent success rates.

PMID- 17214219
TI  - [Gastrointestinal infections due to Clostridium difficile].

PMID- 17214220
TI  - [Accidental exposure to blood and biological fluids].

PMID- 17214221
TI  - [Headaches].

PMID- 17214222
TI  - [Parenteral nutrition].

PMID- 17214223
TI  - [Interpersonal touch in surgery].

PMID- 17214224
TI  - [Mathematic exercises in pediatric doses].

PMID- 17214225
TI  - [Nursing management in oncology].

PMID- 17214226
TI  - [Infectious isolation].

PMID- 17214227
TI  - [Theatrical experience in the emergency room of a Parisian academic medical
      center].

PMID- 17214228
TI  - [Treatment after accidental blood exposure].

PMID- 17214229
TI  - [Scintigraphy, a functional imaging technique].

PMID- 17214231
TI  - [Prostate cancer in the elderly patient].
AB  - Although malignant tumours occur at all ages, cancer disproportionately strikes
      individuals in the age group 65 years and older. The increasing statistical life
      expectancy of men together with the introduction of prostate specific antigen
      (PSA) as a screening tool have both contributed to a rising number of elderly men
      with a diagnosis of prostate cancer. Age is generally considered to be a key
      prognostic factor in terms of therapeutic decision making, perhaps as important
      as PSA level and Gleason score. Even in men over 70 years, treatment without
      curative intent may deprive frail patients of years of life. When considering
      local treatment, strong consideration should be given to radical surgery. Modern
      radical prostatectomy is associated with low perioperative morbidity, excellent
      clinical outcomes as well as long term disease control. Besides, overdiagnosis
      has led to the concept of expectant management for screening-detected small
      volume, low grade disease, with intention of providing therapy for those men
      experiencing disease progression.

PMID- 17214230
TI  - [Biological markers of prostate cancer].
AB  - Screening for prostate cancer is currently based on the assessment of blood
      prostate specific antigen (PSA). Although PSA was shown to be an adequate tool in
      prostate cancer screening, beginning from 4.0 ng/mL, its specificity is less
      significant. In men with a PSA between 4.0 and 10 ng/mL its predictive value is
      low. Therefore, there is a need for new instruments likely to improve the
      specificity of blood PSA levels between 4.0 and 10 ng/mL and the screening for
      prostate cancer in subjects with low PSA. Recent data are reviewed.

PMID- 17214232
TI  - [Risk factors for positive surgical margins following radical prostatectomy:
      review].
AB  - The presence of positive surgical margins on radical prostatectomy specimen is an
      adverse prognostic factor. Parameters supposed to influence surgical margin
      status includes pathology method analysis, surgical technique, tumoral and non
      tumoral patient parameters, and neoadjuvant hormonal therapy. Regarding the
      surgical technique, surgeon's experience and neuro-vascular bundles preservation
      are the most important factors of margin status, whereas surgical approach,
      bladder neck conservation, intraoperative frozen analysis, and bleeding are minor
      factors. Non tumoural patient parameters influencing surgical margin status
      include patient's age and weight, and prostate gland weight. For tumoural
      parameters, pathological stage and tumour volume are more important factors than
      the tumor grade and PSA. Five preoperative tumoral risk factors of positive
      surgical margins are particularly important, including abnormal digital rectal
      examination, preoperative PSA 10 ng/mL, biopsy Gleason score >7, number of
      positive biopsy cores > or = 2, and suspicion of extraprostatic extension on
      radical prostatectomy specimen.

PMID- 17214233
TI  - [Assessment of male infertility].
AB  - The diagnosis of male infertility requires methodical approach which is primarily
      clinical, aimed at identifying all potential factors. Biological and radiological
      assessments allow diagnosis confirmation, and evaluation of both prognosis and
      therapeutic strategy.

PMID- 17214234
TI  - [Non-germinal tumours of the testicle].
AB  - The great variety of non germinal testis tumours and their rarity explain the
      difficulties of a specific therapeutic management. The analysis of the most
      important varieties of tumours allows identifying an overall trend in both
      diagnosis and therapy.

PMID- 17214235
TI  - [Laparoscopic pyeloplasty].
AB  - Ureteropelvic junction (UPJ) obstruction in adults is usually symptomatic,
      secondary, and it tends to progress. Surgical correction of obstructed UPJ is
      necessary to preserve the renal function of the affected kidney. Pyeloplasty as a
      surgical management for UPJ obstruction in adults has proven its efficacy with
      high success rates on long-term results. Laparoscopic pyeloplasty in the
      management of primary or secondary UPJ obstruction in adults technically
      duplicate the open surgical technique. Laparoscopic pyeloplasty has developed to
      match success, morbidity and complication rates of open surgical pyeloplasty.
      However it was shown that laparoscopy had consistently a shorter convalescence
      than open surgery. Endopyelotomy is utilized to manage UPJ obstruction. Early
      results for endopyelotomy were promising but long-term results were not
      encouraging. In the management of UPJ obstruction in adults, long-term success
      rates for laparoscopic pyeloplasty were found to be superior to those of
      endopyelotomy. Therefore we believe that laparoscopic pyeloplasty will become as
      a standard management for UPJ obstruction in adults.

PMID- 17214236
TI  - [Replacement enterocystoplasty in man (except Hautmann): principles and technical
      considerations].
AB  - Orthotopic urinary reservoir using a bowel segment has become the most favoured
      form of diversion after radical cystectomy. Ideal neobladder has to (i) store the
      urine with a low pressure bladder substitute, (ii) protect the upper urinary
      tract and (iii) provide a better quality of life enabling volitional voiding. A
      lot of techniques have bee described to construct a reservoir, however, all of
      them are based on the principle of intestinal loop detubulation. Many intestinal
      segments have been used, but ileum seems to be preferred in Europe. The upper
      urinary tract is mainly protected by a low neobladder pressure, rather than an
      additional antireflux flap-valve-type implantation technique which may increase
      the risk of uretero-enteric stricture. No significant difference in functional
      outcome can be observed among the several techniques. In selected cases,
      orthotopic bladder replacement is well tolerated and feasible and appears to be
      the gold standard after cystectomy.

PMID- 17214237
TI  - Heart failure: improving the continuum of care.
AB  - In the United States (US), heart failure (HF) is the leading medical condition
      resulting in hospital admission. Despite advances in treatment, the number of HF
      deaths has continued to increase. At Carolinas Medical Center (CMC), more than
      950 annual HF admissions provided an opportunity to examine morbidity, mortality,
      and readmission rates. Within the facility there exist two HF disease management
      programs treating more than 1500 patients annually. Through a systematic approach
      to identify the root causes of morbid and less severe complications, the facility
      addressed process improvement steps to positively impact HF treatment. Included
      in these strategies was a link to the outpatient continuum of care created for
      the HF patient. An examination of the HF program revealed the care to be
      fragmented, both organizationally and physically. A majority of readmissions
      could be prevented through closer patient follow-up and more aggressive therapy.
      Intensive education for staff about the disease management process, medication
      interventions, smoking cessation, and nutrition counseling was lacking. An
      interdisciplinary committee, with strong administrative support, was established
      to evaluate the current program and recommend changes. Delivery of patient care
      was changed to an integrated care management system model identifying the root
      causes of the most prevalent operational and clinical deficits. Process
      improvement steps were immediately implemented. The 30-day readmission rate (all
      causes) decreased from 18% to 6.1%, the readmission rate for HF decreasedfrom
      7.3% to 1.7%, mortality declined by 25%, and morbid complications decreased by
      35%. Evaluation of processes and clinical outcomes are ongoing in order to
      develop strategies for even greater improvement within the HF program.

PMID- 17214238
TI  - Enhancing victim safety through collaboration.
AB  - Elder abuse is associated with morbid and lethal outcomes. In some cases of elder
      abuse, particularly involving domestic violence, uninformed or improperly
      executed interventions can result in serious harm to the victims. Professionals
      from various disciplines may themselves be at risk during encounters with
      perpetrators. This chapter provides an overview of potentially dangerous
      scenarios of elder abuse such as homicide, homicide/suicide, strangulation, and
      stalking. Intervention strategies such as lethality assessments and safety
      planning are described. A case scenario illustrates the value of an
      interdisciplinary response to enhance victim safety. This chapter reviews
      potential lethality factors and the steps that can be taken to enhance the safety
      of victims, their families, and the professionals who serve them.

PMID- 17214239
TI  - Medicaid planning, estate recovery, and alternatives for long-term care
      financing: identifying the ethical issues.
AB  - In anticipation of the escalating costs of long-term care, consumers and the
      federal and state governments are engaging in a variety of strategies intended to
      preserve the financial solvency of the respective parties. For the consumer, this
      may mean planning in a way designed to maximize one's potential future
      eligibility for government support, whereas the federal government tries to limit
      those planning activities inspired by public benefits considerations and the
      states attempt to recover their long-term care expenses from the estates of
      deceased consumers whose long-term care needs the state had earlier supported.
      All of these strategies have important and controversial public policy
      implications. The public policy debate surrounding these strategies ought to be
      ethically informed. This article sets out to identify and outline some of the
      main ethical questions engendered by individual Medicaid planning on one hand,
      and state estate recovery efforts on the other. It concludes that neither of
      these approaches to the challenge of long-term care financing is very ethically
      palatable.

PMID- 17214240
TI  - Tube feeding in advanced dementia: an exploratory survey of physician knowledge.
AB  - The administration of artificial nutrition by means of a percutaneous endoscopic
      gastrostomy (PEG) tube in older persons in the advanced stages of dementia is
      commonplace, yet the treatment is associated with significant treatment burdens
      and unclear benefits in this population. In addition, there is wide and
      unexplained geographic variability in the use of PEG in advanced dementia, which
      may stem partly from physicians' lack of understanding about its indications,
      risks, benefits, and effect on quality of life in advanced dementia. This study
      was a mail survey undertaken to assess physician knowledge regarding tube feeding
      in advanced dementia and explore whether certification in geriatrics or other
      physician characteristics are associated with physician knowledge. To assess
      knowledge about tube feeding, we asked participants to rate the importance of
      commonly cited, but non-evidence based, indications for tube feeding in advanced
      dementia, including recurrent aspiration pneumonia, abnormal swallowing
      evaluations, abnormal nutritional parameters, preventing an uncomfortable death,
      and others. Discrepancies between physician knowledge and current evidence
      regarding tube feeding in advanced dementia were found, indicating a need for
      improved education ofprimary care physicians in order to ultimately provide
      better end-of-life care for patients with advanced dementia.

PMID- 17214241
TI  - Financial preservation and protection for the elderly.
AB  - This article's objective is to share various financial approaches, facts, and
      opinions that may be helpful to those assisting the elderly. This document has
      four main sections: a tool kit of ideas for dealing with financial affairs;
      investment facts, financial planning, and recommendations--a road map for
      planning and investing; long-term care insurance--who might benefit, and; toward
      the end, steps to take to preserve wealth when life expectancy is short.

PMID- 17214242
TI  - Long-term care for the elderly and persons with disabilities in Saratov Region,
      Russia.
AB  - In Russia, charity started developing into a public welfare system after the
      transition to Christianity. Peter the Great played an important role in
      establishing the social welfare system. According to his decree from June 8,
      1701, "charity houses for beggars, sick people, and elderly" started their
      existence. During the reign of Catherine II, also known as Catherine the Great,
      decrees about public welfare were approved at regional levels.

PMID- 17214243
TI  - Dynamics of patient targeting for care management in Medicaid: a case study of
      the Durham Community Health Network.
AB  - Targeting appropriate patients for care management is crucial to maximizing
      quality of care and cost-effectiveness in Medicaid care management programs. This
      study examined patient characteristics predicting selection for care management
      pre- and postmanagement changes at the Durham Community Health Network (DHCN),
      one of North Carolina's Medicaid primary care management networks. From the
      beginning, care managers were directed to target asthmatics, diabetics, and high
      volume utilizers of health care, using an array of markers to identify patients
      who needed management. In 2003, the state reinforced its focus on chronic disease
      and high utilizers, and new management at DCHN began emphasizing the use of
      protocols for patient targeting. This study examined the relative effects of
      patient demographics, diagnoses, PCP group, and health care utilization as
      predictors of patient selection before and after these changes.

PMID- 17214244
TI  - Nursing care management of older adults with HIV/AIDS and chronic depression.
AB  - Older adults with human immunodeficiency virus/acquired immunodeficiency syndrome
      (HIV/AIDS) and chronic depression constitute a growing population of individuals
      in need of quality nursing care management. Although the small amounts of
      research currently available focus on both middle-aged and older adults living
      with these chronic conditions, this article offers specific suggestions for the
      nursing care of older adults who have been diagnosed with HIV, have experienced
      the progression of HIV to AIDS, and who have lived with chronic depression prior
      to the onset of HIV/AIDS. Given the increasingly significant role that nurses
      play in the lives of older adults with chronic health conditions, this article
      aims to provide nurses with a number of interventions associated with 10 nursing
      diagnoses pertinent to the care of older adults with HIV/AIDS and chronic
      depression.

PMID- 17214245
TI  - The fallacy of late-life divorce in Japan.
AB  - Late-life divorces in Japan, that is, divorces by couples with more than 20
      years' duration of marriage at the time of divorce, have become increasingly
      conspicuous since in the mid-1990s. However, an increase in the number of late
      life divorces is not the same as an increase in the divorce rate. That is, the
      conspicuous phenomenon of late-life divorces may not reflect the true nature of
      the institution of divorce. It may be a fallacy of late-life divorce in Japan
      today. This is the starting point of the present study. Five major findings have
      emerged. First, late-life divorces did increase dramatically over the recent
      past. Second, late-life divorces will continue to increase after 2007, when the
      new old-age pension division scheme for couples who pursue divorce will be in
      effect. Third, the increment in late-life divorce cases is due primarily to the
      baby-boomers born between 1947 and 1949 who are pursuing such late-life divorces.
      Fourth, as the duration of marriage increases, Japanese married couples are less
      inclined to pursue divorce. Fifth, the reasons for late-life divorces differ from
      those expressed for divorces in general. It is hoped that these findings will
      provide valuable insights for Japanese couples married for many years who may
      wish to reconsider and to reconstruct their marital relationship for the better.

PMID- 17214246
TI  - Reflections on 12 years of facilitating Alzheimer's Caregiver Support Groups.
AB  - This article discusses the background, characteristics, caregiver benefits, and
      facilitator rewards of Alzheimer's Caregiver Support Groups conducted over a 12
      year period. The objective being to motivate more professionals to start similar
      groups to increase supports for family members in the face of this devastating
      progressive disease and/or to encourage clients to consult their local
      Alzheimer's Association to find caregiver groups already formed in or around
      their community. Providing or locating this service is strongly advocated by both
      the caregivers interviewed and the facilitator.

PMID- 17214248
TI  - Dignity for all: affordable assisted living.
AB  - In 2026, the first of the baby boomers, including Presidents Clinton and Bush,
      will reach the age of 80, the average age of residents currently in assisted
      living facilities. In her book The Denial of Aging: Perpetual Youth, Eternal
      Life, and Other Dangerous Fantasies, Muriel Gillick proposes that the baby
      boomers will seek assisted living as an alternative to nursing home care. But
      what about that portion of the population not able to afford the high cost of
      private assisted living? What option will be available to the low-asset/low
      income population in lieu of nursing home care?

PMID- 17214247
TI  - Myths and realities of aging.
AB  - As the aging population expands, it will become increasingly important for health
      care providers to become aware of and sensitive to the needs and concerns of
      older adults. Ageism is a term that describes negative stereotyping of older
      adults and discrimination because of older age. Health concerns and symptoms in
      the elderly may be overlooked or dismissed as part of the normal aging process.
      Consequently, several conditions in olders adults are significantly
      underdiagnosed and undertreated Misconceptions about aging frequently encountered
      in medicine and in society at large include issues involving sexuality, sleep
      disturbance, depression, cognitive impairment, and substance abuse. We can learn
      to recognize ageist notions that influence medical practice. Perhaps by becoming
      more aware of myths and realities of aging, we can improve the health and quality
      of life of our elderly patients.

PMID- 17214249
TI  - Fair rationing is essentially local: an argument for postcode prescribing.
AB  - In this paper I argue that resource allocation in publicly funded medical systems
      cannot be done using a purely substantive theory of justice, but must also
      involve procedural justice. I argue further that procedural justice requires
      institutions and that these must be "local" in a specific sense which I define.
      The argument rests on the informational constraints on any non-market method for
      allocating scarce resources among competing claims of need. However, I resist the
      identification of this normative account of local justice with the actual
      approach to local decision-making taken within the UK National Health Service. I
      illustrate my argument with reference to the case of provision of In Vitro
      Fertilisation within the UK NHS.

PMID- 17214250
TI  - Resource allocation and the duty to give reasons.
AB  - In a much cited phrase in the famous English 'Child B' case, Mr Justice Laws
      intimated that in life and death cases of scarce resources it is not sufficient
      for health care decision-makers to 'toll the bell of tight resources': they must
      also explain the system of priorities they are using. Although overturned in the
      Court of Appeal, the important question remains of the extent to which health
      care decision-makers have a duty to give reasons for their decisions. In this
      paper, I examine the philosophical foundations of the legal obligation to give
      reasons in English law. Why are judges sometimes supportive of the imposition of
      a duty to give reasons and sometimes not? What is it about the context of life
      and death health care allocation problems that makes it unsuitable in their view
      for such a duty; and is this stance justified? What is it to give a reason for a
      decision? I examine Frederick Schauer's account of reason-giving in terms of
      generalisation and commitment and I suggest that it provides an overstated
      account of what giving a reason commits one to. I go on to examine an idea of
      judicial creation: that where value judgements are "inexpressible" there is a
      strong reason not to impose a duty to give reasons on to public bodies. The
      strongest case for a duty to give reasons is in terms of the value of respect for
      citizens. I argue that there is nothing in the very nature of reason-giving that
      ought to preclude the imposition of such a duty in this context, but concede that
      there is a serious danger of legalism that could result in a hamstringing of
      health care decision-making. It is up to judges and lawyers to seek to avoid this
      danger.

PMID- 17214251
TI  - Access, equity and the role of rights in health care.
AB  - Modern health care rhetoric promotes choice and individual patient rights as
      dominant values. Yet we also accept that in any regime constrained by finite
      resources, difficult choices between patients are inevitable. How can we balance
      rights to liberty, on the one hand, with equity in the allocation of scarce
      resources on the other? For example, the duty of health authorities to allocate
      resources is a duty owed to the community as a whole, rather than to specific
      individuals. Macro-duties of this nature are founded on the notion of equity and
      fairness amongst individuals rather than personal liberty. They presume that if
      hard choices have to be made, they will be resolved according to fair and
      consistent principles which treat equal cases equally, and unequal cases
      unequally. In this paper, we argue for greater clarity and candour in the health
      care rights debate. With this in mind, we discuss (1) private and public rights,
      (2) negative and positive rights, (3) procedural and substantive rights, (4)
      sustainable health care rights and (5) the New Zealand booking system for
      prioritising access to elective services. This system aims to consider:
      individual need and ability to benefit alongside the resources made available to
      elective health services in an attempt to give the principles of equity practical
      effect. We describe a continuum on which the merits of those, sometimes
      competing, values--liberty and equity--can be evaluated and assessed.

PMID- 17214252
TI  - Law, patient's rights and NHS resource allocation: is Eurostar the answer?
AB  - Historically attempts to use the courts as a means of challenging decisions to
      refuse NHS resources have met with little success. However two recent
      developments, that of the Human Rights Act 1998 and the development of European
      Union law through the application of Article 49 of the EC Treaty have provided
      the prospect for a challenge to this position. This article examines the impact
      of a recent case that of Watts v Bedford PCT in which a woman sought to by-pass
      NHS waiting lists by seeking treatment in France and then claimed reimbursement
      of the cost of the operation and the possible impact of this case in the context
      of patients's rights and resource allocation.

PMID- 17214253
TI  - An empirical assessment of social structural and cultural change in clinical
      directorates.
AB  - The results of two observational studies of clinical directorates (CDs) are
      presented. The paper exposes fresh perspectives about the management of hospitals
      and CDs, and suggests that the most important axis on which hospital decision
      making rests continues to be profession rather than the CD, even though CDs are
      designed at least in part to mitigate professional tribalism and bridge
      professional divides. In empiricising social structural and cultural theories it
      seems clear that changes to the prescribed organisational framework, which CDs
      represent, have had negligible effects on behaviour. This being the case, the
      paper questions the benefits alleged to have accrued from establishing CDs and
      calls for more effective, micro-behavioural change strategies than merely
      altering the structure.

PMID- 17214254
TI  - The role of "evidence" in recovery from mental illness.
AB  - Evidence-based practice (EBP), a derivative of evidence-based medicine (EBM), is
      ascendant in the United States' mental health system; the findings of randomized
      controlled trials and other experimental research are widely considered
      authoritative in mental health practice and policy. The concept of recovery from
      mental illness is similarly pervasive in mental health programming and advocacy,
      and it emphasizes consumer expertise and self-determination. What is the
      relationship between these two powerful and potentially incompatible forces for
      mental health reform? This paper identifies four attempts, in the mental health
      literature, to delineate the role of "evidence" in recovery. One is the strong
      version of evidence-based practice-an applied science model-and three others
      address weaknesses in the first by limiting the authority of probabilistic
      findings. The paper also offers a fifth version, based on the concept of
      communicative accountability, which is derived from Habermas' work on
      communicative action. The fifth version responds to the other four and emphasizes
      learning, disclosure and respect in clinical and other helping relationships.

PMID- 17214255
TI  - Public, experts, and acceptance of advanced medical technologies: the case of
      organ transplant and gene therapy in Japan.
AB  - In 1997, after long social debates, the Japanese government enacted a law on
      organ transplantation from brain-dead bodies. Since 1993, on gene therapy,
      administrative agencies have issued a series of guidelines. This study seeks to
      elucidate when people became aware of the issues and when they formed their
      opinions on organ transplant and gene therapy. At the same time, it aims to
      examine at which point in time experts, those in university ethical committees
      and in academic societies, consider these technologies became accepted among the
      public. A self-administered questionnaire was sent by mail to a stratified random
      sampling of 3,000 people nationwide in Japan. Another questionnaire was sent both
      to the member societies of the Japanese Association of Medical Sciences and to
      the ethical committees of all the medical schools in Japan. Results of the
      surveys indicated that many of the public remained undecided on the desirability
      of organ transplant or gene therapy at the time of enactment of official
      guidelines. A substantial part of them formed their opinions in subsequent
      periods, especially around the time of first implementation and thereafter.
      Experts of the academic societies and of the university ethical committees
      regarded the time of implementation as an important factor in the acceptance of
      the technologies in society. Since many people formed their opinion during the
      period of technological implementation, communications efforts to facilitate
      public understanding of science and technology, as well as to advance practical
      discussion on policy alternatives in this period can play a key role in
      determining the fate of technological innovation and ethical debates in medicine.

PMID- 17214257
TI  - New Australian governance faces old legal impediments.
AB  - This article provides a critique of the controlling legal paradigm in Australia
      from related scientific and quality management perspectives. It shows key legal
      requirements are prescientific and hinder attainment of community health and
      sustainable development goals. It discusses regional arrangements which appear
      necessary to achieve national aims and the potential of a duty of care regulatory
      approach, in which dispute resolution is conceptualised as community service,
      like health or education provision.

PMID- 17214256
TI  - Solidarity: a (new) ethic for global health policy.
AB  - This article explores solidarity as an ethical concept underpinning rules in the
      global health context. First, it considers the theoretical conceptualisation of
      the value and some specific duties it supports (ie: its expression in the
      broadest sense and its derivative action-guiding duties). Second, it considers
      the manifestation of solidarity in two international regulatory instruments. It
      concludes that, although solidarity is represented in these instruments, it is
      often incidental. This fact, their emphasis on other values and their internal
      weaknesses diminishes the action-guiding impact of the solidarity rules. The
      global health and human subject research scene needs a completely new instrument
      specifically directed at means by which solidarity can be achieved, and a
      reformed infrastructure dedicated to realising that value.

PMID- 17214258
TI  - Principlism revisited: response to Simon Waltho.
AB  - We respond to the comments provided on our paper 'Principles help to analyse but
      often give no solution-secondary prevention after a cardiac event' by Simon
      Waltho, and highlight points of clarification.

PMID- 17214259
TI  - Tympanic reperforation in myringoplasty: evaluation of prognostic factors.
AB  - OBJECTIVES: The most frequent failure in myringoplasty is reperforation. This
      complication appears at a rate of 7% to 27%. The aim of this study was to
      evaluate the importance of the principal prognostic factors to the risk of
      reperforation. METHODS: This is a study of prognosis based on an inception
      cohort. The prognostic factors considered in the study refer to clinical and
      surgical aspects; follow-up ranged from 5 to 7 years (mean, 68 months). The study
      was performed on 212 patients with or without otorrhea who underwent operation
      for tympanic perforation. All subjects underwent myringoplasty by means of an
      underlay or overlay technique depending on the size and site of the perforation.
      RESULTS: Healing of the tympanic perforation was obtained in 182 cases (86%).
      Age, otorrhea, status of the contralateral ear, and conductive hearing loss did
      not significantly affect the outcome of surgery. On the other hand, time from
      surgery, the site of perforation, the type of anesthesia, the approach, the
      surgical technique, and the type of graft were significantly related to the
      outcome. CONCLUSIONS: In the analysis of our results, the surgical approach
      proved to be the principal prognostic factor in the anatomic outcome of
      myringoplasty. The results obtained suggest that the principal factors
      influencing the outcome of myringoplasty are technical and not clinical.

PMID- 17214260
TI  - Stapedotomy with microdrill or carbon dioxide laser: influence on inner ear
      function.
AB  - OBJECTIVES: A prospective randomized audiological analysis of 336 otosclerosis
      operations was conducted to compare the evolution of bone conduction thresholds
      after primary stapedotomy with two different techniques to open the footplate:
      microdrill and carbon dioxide laser stapedotomy. METHODS: To monitor the inner
      ear function, we compared the preoperative bone conduction thresholds with the
      postoperative levels at day 2, week 2, week 6, and month 6. Evolution of the bone
      conduction was compared for the two studied groups (laser versus microdrill).
      RESULTS: An average bone conduction loss of 1.8 dB was measured at day 2 for the
      middle frequencies (0.5, 1, and 2 kHz). At 4 kHz, a bone conduction loss of 7 dB
      was found. The bone conduction thresholds measured in the first and second months
      after surgery showed a gradual recovery with overclosure as the end result.
      CONCLUSIONS: Our results confirm the transient depression of inner ear function
      in the immediate postoperative period, with recovery within the first weeks after
      surgery. In the studied population, no statistically significant difference was
      found between the two techniques that were used to make the calibrated hole
      (laser versus microdrill). These results demonstrate that both techniques possess
      the same early effect regarding inner ear function. The authors hypothesize that
      an early inflammatory reaction could be the cause of the transient bone
      conduction shift.

PMID- 17214261
TI  - Outcome of endoscopic management of extensive laryngotracheal stenosis.
AB  - OBJECTIVES: When performing endotracheal intubation or tracheotomy in unconscious
      patients in emergent situations, one should consider the possibility of the later
      complication of laryngotracheal stenosis, which can result in difficulties with
      decannulation. We analyzed the clinical features of laryngotracheal stenosis to
      search for its possible etiologic factors and its proper preventive methods.
      METHODS: The medical records of 249 cases of laryngotracheal stenosis out of
      2,208 patients who underwent tracheotomy in our hospital during the past 12 years
      were retrospectively reviewed regarding several parameters, such as the duration
      of endotracheal intubation, site of tracheostoma, site of stenosis, treatment
      method, and so forth. RESULTS: Non-otolaryngologists had a tendency to place the
      tracheostoma at a higher level of the trachea. We identified technical
      precautions that should be taken into consideration in performing an emergency
      tracheotomy. Bronchoscopic evaluation and tracheal stent insertion was the most
      commonly used treatment method. Successful decannulation was achieved in about
      70%, and was especially frequent in patients whose endotracheal intubation was
      less than 20 days. CONCLUSIONS: It is desirable that the duration of endotracheal
      intubation be limited to less than 20 days. A database of patients who undergo
      tracheotomy should be submitted to careful follow-up to diagnose early
      development of laryngotracheal stenosis and to prevent long-term complications.

PMID- 17214262
TI  - Office-based and microlaryngeal applications of a fiber-based thulium laser.
AB  - OBJECTIVES: The carbon dioxide (CO2) laser is the premier dissecting instrument
      for hemostatic cutting and ablation during endolaryngeal surgery. However,
      microlaryngeal tangential dissection and office-based photoablation have been
      limited by the lack of a fiber-based delivery system. To address this limitation,
      a new laser was designed, which is a diode-pumped solid-state laser with a
      thulium-doped yttrium-aluminum-garnet laser rod. It produces a continuous-wave
      beam with a wavelength of 2013 nm and a target chromophore of water. This new
      laser functions similarly to a CO2 laser with the benefit of being delivered
      through a small glass fiber (0.365 to 0.550 mm). METHODS: A prospective pilot
      trial was done in 74 cases to explore applications of the new thulium laser.
      Thirty-two procedures were done with the laser used as an ablating instrument and
      topical anesthesia through a flexible laryngoscope (papillomatosis, 20;
      microinvasive carcinoma, 6; benign supraglottic lesions, 3; edema, 2; granuloma,
      (1). Forty-two procedures were done with the laser used as a cutting or ablating
      instrument for microlaryngeal dissection and general anesthesia. These included
      27 partial laryngeal resections (supraglottis, 15; glottis, 10; subglottis, (2)
      and 8 posterior glottic laryngoplasties. The laser was also used as an ablative
      instrument during microlaryngoscopy in 7 cases. RESULTS: The thulium laser was
      used effectively in all cases, under both local and general anesthesia. In
      microlaryngeal dissection, electrocautery was not needed to control bleeding,
      even during cutting in the highly vascular paraglottic space. No complications
      related to the use of the thulium laser were experienced in any case.
      CONCLUSIONS: Because of the fiber-based delivery system, the 2013-nm continuous
      wave thulium laser shows substantial promise for tangential dissection during
      microlaryngoscopy and soft tissue photoablation during office-based flexible
      laryngoscopy. Hemostasis was judged to be superior to experiences with the CO2
      laser. In this pilot study, performing en bloc laryngeal cancer resection
      procedures was facilitated by use of the thulium laser.

PMID- 17214263
TI  - Relationship between fluoroscopic and manometric measures of pharyngeal
      constriction: the pharyngeal constriction ratio.
AB  - OBJECTIVES: The gold standard objective measure of pharyngeal strength is
      pharyngeal manometry. We have developed an objective fluoroscopic measure of
      pharyngeal strength, the pharyngeal constriction ratio (PCR). A high PCR
      indicates poor pharyngeal constriction. The objective of the current study was to
      evaluate the correlation between the PCR and peak pressures on pharyngeal
      manometry. METHODS: The charts of 20 consecutive individuals who underwent a
      dynamic fluoroscopic swallow evaluation and pharyngeal manometry at the Center
      for Voice and Swallowing of the University of California, Davis, were
      retrospectively reviewed. Information regarding patient demographics, diagnoses,
      PCR, and manometric pharyngeal peak pressures was abstracted. The correlation
      between the PCR and pharyngeal pressure was determined with the Pearson
      correlation coefficient. RESULTS: The mean (+/-SD) age of the cohort was 63 +/-
      11 years. Fourteen of the 20 patients (70%) were male. The most common diagnoses
      were reflux (7 of 20) and cerebrovascular accident (4 of 20). The mean PCR was
      0.26 +/- 0.31. The mean pharyngeal pressure was 83 +/- 43 mm Hg. The correlation
      between the PCR and pharyngeal pressure was -0.70 (p < .01). CONCLUSIONS: There
      was a high inverse correlation between the PCR and the peak pharyngeal pressure
      on manometry (-0.70). The PCR appears to be a valid objective surrogate measure
      of pharyngeal strength.

PMID- 17214264
TI  - Thyroidectomy for Graves' disease: a case-control study.
AB  - OBJECTIVES: The most common treatment for Graves' disease in the United States is
      radioactive iodine. Surgery is performed rarely. The surgery for Graves' disease
      is usually considered technically difficult. Our goal was to assess the
      differences in outcomes in patients with Graves' disease who underwent
      thyroidectomy and in patients without Graves' disease who underwent the same
      procedures. METHODS: A retrospective chart review was performed of patients who
      underwent surgery for Graves' disease between 1997 and 2005. A control group of
      age-matched and thyroid size-matched patients who underwent thyroidectomy for a
      diagnosis other than Graves' disease was identified. The groups were
      statistically compared with respect to length of hospital stay, operative time,
      and estimated blood loss. Comparison with the published literature was also
      performed. RESULTS: Eleven patients underwent thyroidectomy for a diagnosis of
      Graves' disease. The operative time, estimated blood loss, and length of
      hospitalization did not differ significantly from those of the control patients.
      Three of the 4 complications that occurred, however, were in the 3 patients with
      persistent hyperthyroidism despite medical therapy at the time of surgery.
      CONCLUSIONS: Thyroidectomy may be performed relatively safely for selected
      euthyroid patients with Graves' disease. In those with persistent hyperthyroidism
      at surgery, there were more complications.

PMID- 17214265
TI  - Transient evoked otoacoustic emissions in vestibular neuritis.
AB  - OBJECTIVES: Partial or total degeneration of the vestibulocochlear anastomosis at
      its takeoff from the saccular ganglion and regenerating efferent neural buds
      under the cochlear outer hair cells (OHCs) have been found in the temporal bones
      of human patients with a history of vestibular neuritis (VN). We sought to test
      whether VN has any functional impact on the ipsilateral OHCs by means of
      transient evoked otoacoustic emission (TEOAE) testing. METHODS: We
      retrospectively analyzed prospectively collected TEOAE data of 28 patients (19
      female, 9 male; age range, 21 to 60 years; median age, 42.5 years). The pure tone
      air conduction hearing thresholds at each standard audiometric frequency (0.125
      to 8 kHz) and the amplitudes of the TEOAEs at the 1-, 2-, 3-, and 4-kHz frequency
      bands were compared between the lesional and contralateral sides by use of the
      nonparametric sign test for 2 paired samples. RESULTS: No significant difference
      was found in the pure tone air conduction hearing thresholds between the lesional
      and contralateral ears at any of the 11 standard tested frequencies. No
      significant difference was found between the TEOAE amplitudes of the lesional and
      contralateral sides. CONCLUSIONS: Subclinical OHC functional impairment is not
      present in VN. Moreover, no apparent significant changes in medial olivocochlear
      bundle resting activity accompany VN.

PMID- 17214266
TI  - Leaving a lasting impression: ear mold impressions as middle ear foreign bodies.
AB  - OBJECTIVES: We describe a series of otologic complications from impression
      material used to make hearing aid molds. METHODS: We examined a retrospective
      case series of patients presenting to a tertiary care academic medical center.
      RESULTS: The presentation, clinical course, and treatment outcomes of 6 patients
      with complications related to ear molds are discussed. These patients had
      preexisting abnormalities in their aural anatomy, including tympanic membrane
      perforations, retraction pockets, and mastoidectomy cavities. CONCLUSIONS:
      Although the majority of patients who have ear canal impressions taken experience
      no adverse outcomes, hearing aid dispensers should perform a thorough history
      taking and physical examination to discern those with abnormal anatomy at risk
      for complications. These patients may benefit from evaluation in conjunction with
      an otolaryngologist.

PMID- 17214267
TI  - Microbiology of intracranial abscesses associated with sinusitis of odontogenic
      origin.
AB  - OBJECTIVES: The unique microbiology of sinusitis of dental origin that is
      associated with intracranial abscesses (IAs) and the correlation between the
      organisms at the two sites has not been reported before. This report describes
      the author's experience during a 30-year period in studying the microbiology of 8
      IAs and their corresponding sinusitis of dental origin. METHODS: Aspirates of pus
      from 8 infected sinuses associated with odontogenic infections and their
      corresponding IAs were studied for aerobic and anaerobic bacteria. Polymicrobial
      flora was found in all 8 sinuses and 7 IAs, and the number of isolates varied
      from 1 to 5. RESULTS: Anaerobic bacteria were isolated from all sinuses and IAs.
      A total of 28 isolates (3.5 isolates per site; 25 strict anaerobic, 1 aerobic or
      facultative, and 2 microaerophilic) were recovered from the sinuses, and 20
      isolates (2.5 isolates per site; 16 strict anaerobic, 1 aerobic or facultative,
      and 3 microaerophilic) were found in the IAs. The bacterial isolates were
      Fusobacterium spp (14), Prevotella spp (11), Peptostreptococcus spp (13),
      microaerophilic streptococci (5), Veillonella parvula (3), and beta-hemolytic
      streptococci group F(2). Concordance in the microbiological findings between the
      sinus and the IA was found in all instances; however, certain organisms were only
      present at one site. CONCLUSIONS: These data illustrate the concordance in the
      organisms recovered from sinusitis of dental origin and their associated IAs and
      confirm the importance of anaerobic bacteria in sinusitis and IAs of dental
      origin.

PMID- 17214268
TI  - Immediate inflammatory response and scar formation in wounded vocal folds.
AB  - OBJECTIVES: Vocal fold scarring is the major cause of voice disorders after voice
      surgery or laryngeal trauma. The role of inflammatory factors in vocal fold wound
      healing and fibrosis has not been adequately investigated. Scarless wound healing
      has been associated with decreased inflammatory responses. To understand scar
      formation and develop reliable treatments, it is necessary to control
      extracellular matrix production and inflammation. Thus, we examined the
      inflammation profile and extracellular matrix production in wounded vocal folds
      in the acute phase of wound healing. METHODS: Vocal fold stripping was performed
      on 30 Sprague-Dawley rats. Vocal fold tissue was collected at 5 time points (4,
      8, 16, 24, and 72 hours). We examined the in vivo messenger RNA expression
      profile of inflammatory factors interleukin 1beta, interferon gamma, tumor
      necrosis factor alpha, nuclear factor kappa beta, transforming growth factor
      beta, and cyclooxygenase 2, as well as hyaluronic acid synthases 1 and 2,
      procollagen subtypes I and III, and elastin synthase in scarred vocal folds after
      injury, compared to normal vocal folds, using real-time reverse transcription
      polymerase chain reaction. RESULTS: The inflammatory factors showed a time
      dependent sequence of expression peaks, starting with interleukin 1beta, nuclear
      factor kappa beta, tumor necrosis factor alpha (4 and 8 hours), and transforming
      growth factor beta (72 hours). Interferon gamma decreased at 24 hours.
      Correspondingly, hyaluronic acid synthase 1 expression peaked first (4 and 8
      hours), whereas hyaluronic acid synthase 2 expression peaked at 16 hours and
      again at 72 hours. Procollagen I expression peaked at 72 hours, whereas
      procollagen III decreased from 8 to 16 hours but peaked at 72 hours.
      Cyclooxygenase 2 expression was elevated, whereas elastin expression remained
      constant. CONCLUSIONS: The results show a clear profile of vocal fold
      inflammation with corresponding changes in extracellular matrix production.

PMID- 17214269
TI  - Characterization of rat spiral ligament cell line immortalized by adenovirus 12
      simian virus 40 hybrid virus.
AB  - OBJECTIVES: Spiral ligament fibrocytes play an important role in inner ear ion
      homeostasis and are classified into several subtypes according to expression of
      specific enzymes such as Na+, K+ -ATPase, Ca++ -ATPase, and carbonic anhydrase.
      Although our understanding of the cell and molecular biology of spiral ligament
      fibrocytes has increased over time, access to these cells still remains a
      significant hurdle hindering future studies. In this study, we aimed to establish
      a rat spiral ligament cell line with minimal disruption of the original
      characteristics. METHODS: The primary spiral ligament fibrocytes were exposed to
      adenovirus 12-simian virus 40 hybrid virus for immortalization. Karyotypic
      analysis was performed after stabilization of the infected cells, and the
      population doubling time was compared to that of the primary cell. The cell line
      was characterized by immunolabeling and electron microscopy. RESULTS: We describe
      the establishment and characterization of a line of type I spiral ligament
      fibrocytes immortalized with an adenovirus 12-simian virus 40 hybrid virus.
      CONCLUSIONS: This cell line can be a useful research tool for investigating the
      role of spiral ligament fibrocytes in homeostasis and inflammation of the inner
      ear.

PMID- 17214270
TI  - Demystifying relevance of homocysteine hypothesis in native Asian Indian
      population.

PMID- 17214271
TI  - DREAM study and its impact on India.

PMID- 17214272
TI  - Hyperhomocysteinemia as a cardiovascular risk factor in Indian women:
      determinants and directionality.
AB  - OBJECTIVE: To assess Homocysteine (Hcy), vitamin B12 and folic acid (FA)
      concentrations in resident Indian women and to study their correlation with
      traditional risk factors for coronary artery disease. MATERIAL AND METHODS: The
      study included 137 consecutive women who attended a health care program (HCP) for
      women at and above 40 years of age (MAITREYI's HCP). Fasting blood samples for
      Hcy, B12 and folate were collected on ice, centrifuged within 1/2 hour and stored
      at -70 degrees C till assayed using a chemiluminescence method. All women
      underwent a screening for their general health profile including cardiovascular
      health. RESULTS: Of the 137 women screened 21 were excluded because of presence
      of factors known to affect Hcy levels (history of existing CAD had hypothyroidism
      or were on multivitamin supplements). The median Hcy, folic acid and vitamin B12
      levels were 9 pmol/L (range 4.2-38.6), 8.8 ng/ml (2.3-31.6 range) and 214 pg/ml
      (100-2400 range) respectively. The prevalence of hyperhomocysteinemia (>15
      pmol/L) was 24.2%. Correlation for continuous variables using spearman's test and
      for categorical variables with chi-square test showed a highly significant
      negative correlation with vitamin B12 (p < 0.001) and FA (p<0.002). Both systolic
      (p < 0.05) and diastolic (p < 0.02) and diastolic blood pressure also showed a
      significant correlation. However, no correlation was found between plasma Hcy and
      blood sugars, lipids, age, body mass index and menopausal status. The CAD risk
      was assessed using Framingham risk scores and this too did not show a correlation
      with plasma Hcy. CONCLUSIONS: A large number of women from the present study had
      hyperhomocysteinemia and were deficient in vitamin B12. A significant negative
      correlation between vitamin B12 and plasma Hcy levels was foundin these older
      women. Most Indian studies including the present one do not show a positive
      correlation between elevated Hcy levels and CAD in spite of a large percentage of
      persons showing elevated homocysteine levels. Since high Hcy levels are
      recognized as an independent risk factor for CAD, these findings of absence of
      correlation between Hcy and CAD as reported in various Indian studies need to be
      explored and explained.

PMID- 17214273
TI  - Vitamin B12 deficiency and hyperhomocysteinemia in rural and urban Indians.
AB  - BACKGROUND: Low vitamin B12 concentration in South Asian Indians is common, but
      the exact prevalence is not known. AIM: To investigate prevalence and
      associations of low vitamin B12 concentration and hyperhomocysteinemia in rural
      and urban Indian men living in and around Pune, Maharashtra. METHOD: We studied
      441 middle-aged men (149 rural, 142 slum and 150 urban middle-class residents,
      mean age 39 y). Data on lifestyle, socio-economic status, nutrition and medical
      history were obtained. Circulating concentrations of vitamin B12, folate,
      ferritin, total homocysteine (tHcy), and haematological indices, and
      cardiovascular risk variables were measured. RESULTS: Median plasma B12
      concentration was low (110 pmol/L): Overall, 67% of men had low vitamin B12
      concentration (<150 pmol/L) and 58% had hyperhomocysteinemia (>15 micromol/L). Of
      the urban middle class, 81% had low vitamin B12 concentration and 79% had
      hyperhomocysteinemia. Low vitamin B12 concentration contributed 28% to the risk
      of hyperhomocysteinemia (population attributable risk) while low red cell folate
      contributed 2%. Vegetarians had 4.4 times (95% CI 2.1, 9.4) higher risk of low
      vitamin B12 concentrations and 3.0 times (95% CI 1.4, 6.5) higher risk of
      hyperhomocysteinemia compared to those who ate non-vegetarian foods frequently.
      Urban middle-class residence was an additional independent risk factor of
      hyperhomocysteinemia (odds ratio 7.6 (95% CI 2.5, 22.6), compared to rural men).
      Low vitamin B12 concentration was related to lower blood haemoglobin
      concentration and higher mean corpuscular volume, but macrocytic anemia was rare.
      CONCLUSION: Low vitamin B12 concentration and hyperhomocysteinemia are common in
      Indian men, particularly in vegetarians and urban middle class residents. Further
      studies are needed to confirm these findings in other parts of India.

PMID- 17214274
TI  - Acute renal failure in the intensive care unit.
AB  - BACKGROUND: Acute renal failure (ARF) in the intensive care unit (ICU) is
      associated with high mortality. A thorough understanding of the clinical spectrum
      of the disease is needed in order to devise methods to improve the final outcome
      due to this problem. AIMS AND OBJECTIVES: The aim of the present study was to
      analyze the clinical spectrum, causes, risk and prognostic factors and final
      outcome of ARF in the setting of ICU. METHOD: This prospective study involved
      patients admitted to ICU during the period between September 2003 to January 2005
      (17 months). Patients who developed ARF during the ICU stay were included in the
      study. The clinical and laboratory data were collected at admission and then on
      daily basis. Data recorded included; patient characteristics, underlying medical
      conditions responsible for ICU admission, dialytic status, need for ventilation,
      total duration of ICU stay, APACHE-III score and final outcome, and these data
      were analyzed for predicting survival using univariate and multivariate analysis.
      RESULTS: Twelve hundred and fifteen (1215) patients were admitted to ICU from
      September 2003 to January, 2005 and 46 (3.79%) patients developed ARF after
      admission to ICU. Mean age of patients was 44.9 +/- 17 years and 56.5% were
      males. Comorbidity was seen in 24 (52%) patients; hypertension (34.7%), diabetes
      mellitus (28.3%), coronary artery disease (30.4%) and chronic kidney disease
      (13%). ARF had developed complicating medical and surgical conditions in 33
      (71.7%) and 11 (23.7%) patients respectively. The etiology of ARF was
      multifactorial and included; hypotension (71.74%), volume depletion (17.4%),
      nephrotoxic drugs (67.39%), and sepsis (69.5%). Multiple organ system failure
      (MOSF) was noted in 63% of cases and dialysis was required in 25 (54.3%)
      patients. Mortality occurred in 63% of patients. MOSF and sepsis were found to be
      significant adverse prognostic factors when multiple logistic regression analysis
      was done. CONCLUSIONS: ARF was seen in 3.79% of cases in our ICU and associated
      with poor prognosis. Presence of sepsis, MOSF, higher APACHE--III scores and
      ventilation need were correlated with higher mortality in ARF patients in the
      intensive care unit.

PMID- 17214275
TI  - Intrapancreatic portal cavernoma.

PMID- 17214276
TI  - Cardiogenic shock and hypothyroidism.

PMID- 17214277
TI  - Management issues in the metabolic syndrome.
AB  - The metabolic syndrome or cardiovascular dysmetabolic syndrome is characterized
      by obesity, central obesity, insulin resistance, atherogenic dyslipidemia, and
      hypertension. The major risk factors leading to this syndrome are physical
      inactivity and an atherogenic diet and cornerstone clinical feature is abdominal
      obesity or adiposity. In addition, patients usually have elevated triglycerides,
      low HDL cholesterol, elevated LDL cholesterol, other abnormal lipid parameters,
      hypertension, and elevated fasting blood glucose. Impaired fibrinolysis,
      increased susceptibility to thrombotic events, and raised inflammatory markers
      are also observed. Given that India has the largest number of subjects with type
      2 diabetes in the world it can be extrapolated that this country also has the
      largest number of patients with the metabolic syndrome. Epidemiological studies
      confirm a high prevalence. Therapeutic approach involves intervention at a macro
      level and control of multiple risk factors using therapeutic lifestyle approaches
      (diet control and increased physical activity, pharmacotherapy - anti-obesity
      agents) for control of obesity and visceral obesity, and targeted approach for
      control of individual risk factors. Pharmacological therapy is a critical step in
      the management of patients with metabolic syndrome when lifestyle modifications
      fail to achieve the therapeutic goals. Anti-obesity drugs such as sibutramine and
      orlistat can be tried to reduce weight and central obesity and jointly control
      the metabolic syndrome components. Other than weight loss, there is no single
      best therapy and treatment should consist of treatment of individual components
      of the metabolic syndrome. Newer drugs such as the endocannabinoid receptor
      blocker,rimonabant, appear promising in this regard. Atherogenic dyslipidemia
      should be controlled initially with statins if there is an increase in LDL
      cholesterol. If there are other lipid abnormalities then combination therapy of
      statin with fibrates, nicotinic acid, or ezetimibe should be considered. For
      insulin resistance, drugs such as thiazolidinediones and renin-angiotensin system
      blockers are available. Available evidence suggests that angiotensin converting
      enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBS) may be more
      beneficial for treatment of hypertension in patients with metabolic syndrome
      compared to others as these drugs also prevent development of diabetes. Patients
      with metabolic syndrome also have elevations in fibrinogen and other coagulation
      factors leading to prothrombotic state and aspirin may be beneficial for primary
      prevention in these patients. The new developments in the treatment of metabolic
      syndrome with drugs, such as peroxisome proliferator-activated receptor (PPAR)
      agonists and cannabinoid receptor-1 antagonists, will broaden the horizons of the
      current treatment options. Fixed-dose combination polypharmacy using a single
      pill is an interesting concept that needs to be evaluated in long-term
      prospective trials in such patients.

PMID- 17214278
TI  - Medical philaely (Medical theme on stamps). Dominique J. Larrey (1766-1842).
      Northern France Ambulance, 1918 stamp, Grenada-1970.

PMID- 17214279
TI  - ARDS complicating scrub typhus in Sub-Himalayan region.
AB  - Scrub typhus is a febrile illness widely endemic in Asia caused by Rickettsiae
      tsutsugamushi in which humans are accidental hosts. If there is delay in the
      initiation of the appropriate antimicrobial therapy patient may present with
      serious complications. We report three cases that presented in emergency with
      acute respiratory distress syndrome and history of fever for more than one-week
      duration. On investigation all the three patients were positive for Weil Felix
      reaction and showed dramatic response to doxycycline.

PMID- 17214280
TI  - Pulseless cardiomyopathy.
AB  - Takayasu arteritis can have myriads of presentation, depending on site and extent
      of disease. As no age is immune for this disease, it is important to keep a high
      index of suspicion, otherwise the diagnosis can be missed. We hereby describe a
      case of Takayasu arteritis, which presented as dilated cardiomyopathy.

PMID- 17214281
TI  - Multiple cardiovascular involvement in a case of relapsing polychondritis.
AB  - Relapsing polychondritis is a multisystem disease characterized by recurrent
      inflammation of the cartilaginous tissue. Cardiovascular manifestations of
      relapsing polychondritis are rare but are the second most common cause of death
      in these patients. We report a case of relapsing polychondritis who underwent
      aortic valve replacement uneventfully but presented six months later with
      myocardial infarction due to bilateral coronary ostial stenosis.

PMID- 17214282
TI  - Drug related crisis in myasthenia gravis.
AB  - Myasthenia gravis is an autoimmune disorder where antibodies against the
      nicotinic Ach receptor resulting in impaired transmission at the NM junction. A
      number of drugs have been reported to cause neuromuscular blockade and/or to
      increase weakness in myasthenia gravis. We report a case of myasthenia gravis in
      which the calcium channel blocker-nifedipine caused the worsening of the
      symptoms.

PMID- 17214283
TI  - Idiopathic hypoparathyroidism presenting as secondary myelofibrosis.
AB  - Myelofibrosis occurring both in childhood and adulthood is most commonly
      idiopathic, followed by neoplastic infiltration of the bone marrow. We are
      reporting an extremely rare association of idiopathic hypoparathyroidism
      associated with stable secondary myelofibrosis.

PMID- 17214284
TI  - Alkyl succinate poisoning.
AB  - A case of alkyl succinate poisoning is being reported. Oral ingestion of this
      compound led to gastrointestinal tract involvement and central nervous system
      manifestatations suggestive of parkinsonism. The patient recovered completely
      following conservative management without any sequelae.

PMID- 17214285
TI  - Phototoxic drug reaction to gatifloxacin.

PMID- 17214286
TI  - Obscure gastrointestinal bleed--a diagnostic and therapeutic challenge.

PMID- 17214287
TI  - Tuberculous brain abscess--a diagnostic and therapeutic challenge.

PMID- 17214288
TI  - Health impact assessment of particulate matter in Tokyo, Japan.
AB  - Among industrialized countries, Japan still maintains an old set of guidelines
      for particulate matter (PM); therefore, we assessed the public health impacts of
      PM exposure in various situations using data from the Tokyo metropolitan area.
      Subjects were 7.8 million people aged older than 30 years. Based on a linear
      relationship between exposure and health effects, we estimated attributable cases
      of mortality caused by PM. Even at the recent exposure level, the number of
      deaths will occur after both short- and long-term exposure. When the guideline
      for PM2.5 (particles < 2.5 microm in diameter) long-term exposure was set at 12
      microg/m3, we could prevent 8% of all causes mortality or 6,700 deaths in the
      Tokyo metropolitan area per year. This assessment shows that guidelines for long
      term exposure, especially for PM2.5, should be recommended in Japan.

PMID- 17214289
TI  - Rosella parrot exposure as a cause of bird fancier's lung.
AB  - A case of a 30-year-old man who presented with a 2-month history of progressively
      worsening dyspnoea, cough, and reduced exercise tolerance is discussed. A chest x
      ray and computerized tomography of the chest suggested interstitial lung disease,
      which was confirmed on histology of an open lung biopsy. Careful questioning
      revealed that the patient had sustained close exposure to a rosella parrot
      acquired as a pet 9 months prior to presentation, which led to the diagnosis of
      bird fancier's lung. The case, investigations, and outcome are presented. This is
      followed by a discussion on extrinsic allergic alveolitis with particular
      emphasis on the importance of a complete social and environmental history in
      patients presenting with similar respiratory symptoms.

PMID- 17214290
TI  - Calcitropic hormones, bone turnover, and lead exposure among female smelter
      workers.
AB  - To study the association between levels of lead in blood and bone among female
      former smelter workers in Bunker Hill, Idaho, the authors performed a
      longitudinal study using homeostatic regulators of calcium and biomarkers of bone
      turnover. The authors measured participants' blood lead levels (by means of a
      graphite furnace atomic absorption spectrophotometer) and tibia-bone lead levels
      (by means of the 109Cd K x-ray fluorescence system) in 1994 and again in 2000;
      serum ionized calcium, parathyroid hormone, osteocalcin, urinary
      deoxypyridinoline, pyridinoline, and 1, 25-dihydroxyvitamin D were measured.
      After controlling for weight and age, significant predictors of changes in blood
      lead levels from 1994 to 2000 in postmenopausal women were duration of
      employment, higher ionized calcium levels, alcohol consumption, and higher
      parathyroid hormone levels. Predictors of change in tibia-bone lead levels in the
      same group of women were employment in a technical job such as mining and higher
      urinary pyridinoline levels (p < .05). Changes in blood and bone lead levels over
      time were associated with increased bone resorption, especially among
      postmenopausal women.

PMID- 17214292
TI  - Effects of dioxin on metabolism of estrogens in waste incinerator workers.
AB  - The authors measured the concentrations of serum dioxins and urinary estrogen
      metabolites in 57 male waste incinerator workers to determine whether dioxin
      influenced the metabolism of estrogens. Concentrations of serum dioxin levels and
      urinary estrogen metabolites, such as estrone, 17beta-estradiol, 2
      hydroxyestrone, 2-methoxyestrone, 2-hydroxyestradiol, 2-methoxyestradiol, 4
      hydroxyestrone, 4-hydroxyestradiol, 4-methoxyestradiol, 16-hydroxyestrone, and
      estriol from the workers were measured. An analysis of covariance showed that
      mean estriol concentrations, adjusted for confounding factors among 3 serum
      dioxin levels, indicated a progressive increase with increasing serum dioxin
      level: 1.30, 1.41, and 2.02 nmol/mol creatinine at < 30.3, 30.3-39.7, and > 39.7
      pg toxicity equivalent quantity/g lipid, respectively (F = 3.56, p = .036). This
      study showed that dioxin acts to metabolize estrogens to 16-hydroxyestrogens
      rather than to 2- or 4-hydroxyestrogens.

PMID- 17214291
TI  - Effects of temperature and ozone on daily mortality during the August 2003 heat
      wave in France.
AB  - During the summer of 2003, Europe experienced a heat wave that lasted almost 2
      weeks in which high temperatures were accompanied by exceptionally high ozone
      levels. Unfortunately, few studies have examined the effects of temperature and
      ozone simultaneously. The authors use constrained distributed lag models to
      estimate the effects of daily temperature and peak ozone on mortality in 12
      French cities during the heat wave and to estimate the deaths attributable to
      each component. Elevated minimum and maximum temperature and peak ozone all
      increase mortality, with substantial interaction effects between temperature and
      ozone. Researchers expect extreme weather events, along with elevated ozone
      levels and temperatures, to become more common. Our results suggest that ozone
      will be an important contributor to the adverse health effects of such events.

PMID- 17214293
TI  - Rapid detection of sewage sample polioviruses by integrated cell culture
      polymerase chain reaction.
AB  - The authors' objective in this study was to introduce and evaluate integrated
      cell culture polymerase chain reaction (ICC-PCR) as a technique for the rapid
      screening of poliovirus in sewage samples. Researchers are in the last stage of
      poliomyelitis eradication; however, in a densely populated country such as India,
      time is the prime factor in the identification of poliovirus circulation and
      transmission because this virus follows the fecal-oral route for transmission and
      is excreted in nature. The authors used ICC-PCR to detect poliovirus in sewage
      samples, and they compared this nonconventional method with conventional cell
      culture methods to determine sensitivity, accuracy, and the time from sample
      collection to final results. The ICC-PCR method provided results within 4-5 days
      of sewage-sample collection; in contrast, the conventional method takes more than
      18 days to provide such results. The ICC-PCR method proved to be sensitive,
      reproducible, and accurate, as well as rapid in its screening of sewage samples
      for poliovirus. This diagnostic tool may indeed prove quite useful in polio
      eradication.

PMID- 17214294
TI  - [Neurochemical organization of reptilian thalamus. Comparative analysis of vision
      centers in Amniota].

PMID- 17214295
TI  - [Sulfonic effectors of cholinesterases of different origin (Comparison with
      ammonia analogs and specificity of action)].

PMID- 17214296
TI  - [Influence of destabilizing factor on structural and functional hemoglobin
      parameters in fishes. ].

PMID- 17214297
TI  - [Influence of temperature on spontaneous interneuronal activity in grasshoppers
      Tettigonia cantas and Metrioptera roeselii (Orthoptera, Tettigoniidae)].

PMID- 17214298
TI  - [Development of hearing sensitivity and formation of acoustically driven
      defensive behavior of Ficedula hypoleuca].

PMID- 17214299
TI  - [Potential action of allatostatin on quantum mediator secretion in murine
      neuromuscular synapsis. ].

PMID- 17214300
TI  - [Glutamate receptors types defining neurotoxic glutamate action on rat cortex
      neurons].

PMID- 17214301
TI  - [Heterogeneous of blocking mechanism of bronchial constriction following by
      exogenous or endogenous stimulation].

PMID- 17214302
TI  - [Diencephalon organization of sturgeons. Periventricular and rostral regions].

PMID- 17214303
TI  - [Diencephalon organisation of sturgeons. Dorsal Region. Caudal region].

PMID- 17214304
TI  - [Adaptive modification of receptor region of carp Cyprinus Carpio (Cyprinidae,
      Teleostei) taste system after chronic anosmia].

PMID- 17214305
TI  - [Receptor formation in abdominal brain of polychaeta Nereis diversicolor and
      problem of its origin and possible function].

PMID- 17214306
TI  - [Age related peculiarities of the relationship among a functional indicators of
      intracranial hemo- and cerebrospinal fluid dynamics].

PMID- 17214307
TI  - Embodied simulation: from mirror neuron systems to interpersonal relations.
AB  - A direct form of 'experiential understanding' of others is achieved by modelling
      their behaviours as intentional experiences on the basis of the equivalence
      between what the others do and feel and what we do and feel. This modelling
      mechanism is embodied simulation. By means of embodied simulation we do not just
      'see' an action, an emotion, or a sensation. Side by side with the sensory
      description of the observed social stimuli, internal representations of the body
      states associated with actions, emotions, and sensations are evoked in the
      observer, as if he/she would be doing a similar action or experiencing a similar
      emotion or sensation. Mirror neurons are likely the neural correlate of this
      mechanism. The mirror neuron matching systems map the different intentional
      relations in a compressed fashion, which is neutral about the specific quality or
      identity of the agentive/subjective parameter. By means of a shared neural state
      realized in two different bodies that nevertheless obey to the same functional
      rules, the 'objectual other' becomes 'another self'.

PMID- 17214308
TI  - The neuronal basis of empathy and fairness.
AB  - The emerging fields of social neuroscience and neuroeconomics have started to
      investigate the neural foundations of empathy and fairness. Even though not
      frequently linked, both concepts point to humans as altruistic beings who care
      for others. Recently social neuroscientists have measured brain activity
      associated with different empathic processes and revealed common neural responses
      when feeling sensations such as disgust, touch or pain in ourselves, and when
      perceiving someone else being disgusted, touched or in pain. At the same time,
      research in neuroeconomics has used game theoretical paradigms to study our sense
      of fairness. Several functional magnetic resonance imaging (fMRI) studies show
      involvement of anterior insula and anterior cingulate cortex in response to
      unfair compared with fair offers during such monetary exchange games.
      Interestingly, the same brain regions are also involved in empathy for pain or
      disgust of others. More generally, anterior insula cortex is suggested to
      subserve neural representations of feeling and bodily states in the self and may
      play a crucial role for the emergence of social emotions related to others.

PMID- 17214309
TI  - What's fair? The unconscious calculus of our moral faculty.
AB  - This essay argues that much of the research in moral psychology has focused on
      moral performance, on what people do. The study of moral competence, in contrast,
      has largely been ignored. I use the analogy to linguistics as a model for
      exploring our moral competence, and suggest that we are endowed with a moral
      faculty that operates over the causes and consequences of actions. This moral
      faculty is endowed with principles and parameters that are universal. Acquiring a
      particular moral system entails setting the parameters. On this model, emotions
      such as empathy are consequences (as opposed to causes) of unconscious but
      principled moral evaluations.

PMID- 17214310
TI  - Chimpanzees may recognize motives and goals, but may not reckon on them.
AB  - Psychological states play a fundamental role in mediating human social
      interactions. We interpret identical actions and outcomes in radically different
      ways depending on the motives and intentions underlying them. Moreover, we take
      reckoning of ourselves stacked up against others, and ideally make moral
      decisions with others in mind. Recently, evidence has been accumulating
      suggesting that our closest relatives are also sensitive to the motives of others
      and can distinguish intentional from accidental actions. These results suggest
      that chimpanzees interpret the actions of others from a psychological
      perspective, not just a behavioural perspective. However, based on recent
      studies, it is not clear whether chimpanzees have any regard for others, calling
      into the question the point at which fairness and other-regard were used as
      building blocks for full-fledged human morality.

PMID- 17214311
TI  - Empathy-related responding and prosocial behaviour.
AB  - In this paper I differentiate among empathy, sympathy and personal distress and
      discuss the central role of empathy-related responding in positive (including
      moral) development. Empathy-related responding, especially sympathy, is likely an
      important source of prosocial, other-oriented motivation. In fact, empathy
      related responding, especially sympathy, has been associated with prosocial
      behaviour (voluntary behaviour intended to benefit another, e.g. helping,
      sharing); this relation has been obtained for both specific instances of empathy
      related responding and for dispositional sympathy. In addition, sympathy (or
      sometimes empathy) has been linked to relatively high levels of moral reasoning
      and social competence, and to low levels of aggression and antisocial behaviour.
      In my talk, I will review research on the relation of empathy-related responding
      to prosocial behaviour, the consistency of costly prosocial behaviour over time
      and the possible role of sympathy in its consistency, and the relation of empathy
      related responding to moral reasoning, antisocial behaviour and social
      competence. Examples of research, including longitudinal research in our
      laboratory, are provided to illustrate these relations. Because of its close
      relations to social and prosocial responding, an understanding of empathy-related
      responding contributes to efforts to promote children's moral development.

PMID- 17214312
TI  - A social interaction analysis of empathy and fairness.
AB  - This paper advances a social interaction analysis of altruism, as a likely result
      of empathy, and egalitarianism, as a key component of fairness. A social
      interaction analysis is unique in that it (a) focuses on the persons and the
      situation, (b) includes proximal and distal influences (such as personality and
      relational influences, as well as cognitive and emotional processes), (c) yields
      action-reaction patterns that are largely observable and therefore especially
      relevant to learning, and (d) helps conceptualize interpersonal orientations that
      affect behaviour and social interactions. The chapter discusses the ubiquity of
      altruism and egalitarianism in the context of social dilemmas and related
      situations, and concludes that these two orientations are important to theorizing
      and research in various disciplines that seek to understand the motivational
      underpinnings of social interactions in dyads and groups.

PMID- 17214313
TI  - Triggering the intentional stance.
AB  - While humans possess a ready capacity to view a target (biological or otherwise)
      as an intentional agent (i.e. the 'intentional stance'), the conditions necessary
      for spontaneously eliciting these mentalizing processes are less well understood.
      Although research examining people's tendency to construe the motion of geometric
      shapes as intentional has done much to illuminate this issue, due to
      methodological limitations (a reliance on subjective self-report) this work has
      not fully addressed the potentially automatic and obligatory nature of
      mentalizing. Acknowledging this problem, recent research using prelinguistic
      infants, neuroimaging technology and methods that avoid explicit self-report all
      provide unique paths to circumvent this shortcoming. While work of this kind has
      generally corroborated the results of previous investigations, it has also raised
      a number of new issues. One such issue is whether spontaneous mentalizing
      processes for abstract non-biological stimuli are instantiated in the same neural
      architecture as those for realistic representations of intentional biological
      agents. This question is considered in the current chapter.

PMID- 17214314
TI  - Dissociable systems for empathy.
AB  - Empathy is a lay term that is becoming increasingly used in the field of
      cognitive neuroscience. In this paper, it is argued that empathy is a loose
      collection of partially dissociable neurocognitive systems. Two forms of
      'emotional' empathy were considered: First, responding to emotional expressions,
      particularly angry expressions, leading to response reversal. Secondly,
      responding to emotional expressions, particularly fearful and sad expressions,
      leading to stimulus-reinforcement learning. The implications of these forms of
      empathy for understanding specific psychiatric conditions are briefly considered.

PMID- 17214315
TI  - Looking at other people: mechanisms for social perception revealed in subjects
      with focal amygdala damage.
AB  - How does the presence of socially relevant information in the environment
      influence our perception and judgment of other people? We have investigated how
      we direct our gaze to other people's faces, how we use specific features from
      faces to make social judgments about the presumed internal states of others, and
      how these mechanisms are disrupted following pathology. Studies of patients with
      damage to the amygdala have demonstrated a specific impairment in the ability to
      direct gaze towards, and to use information from, the eyes in others' faces. This
      basic impairment may explain the deficient recognition of basic emotions and
      deficient social judgment seen in such patients. Ongoing studies in our
      laboratory examine face-to-face social interactions with real people in an
      attempt to link the above impairments in the laboratory to the dysfunctional
      social cognition seen in everyday life.

PMID- 17214316
TI  - Models of distributive justice.
AB  - Philosophical disagreement about justice rages over at least two questions. The
      most immediate is a substantial question, concerning the conditions under which
      particular distributive arrangements can be said to be just or unjust. The
      second, deeper, question concerns the nature of justice itself. What is justice?
      Here we can distinguish three views. First, justice as mutual advantage sees
      justice as essentially a matter of the outcome of a bargain. There are times when
      two parties can both be better off by making some sort of agreement. Justice, on
      this view, concerns the distribution of the benefits and burdens of the
      agreement. Second, justice as reciprocity takes a different approach, looking not
      at bargaining but at the idea of a fair return or just price, attempting to
      capture the idea of justice as equal exchange. Finally justice as impartiality
      sees justice as 'taking the other person's point of view' asking 'how would you
      like it if it happened to you?' Each model has significantly different
      consequences for the question of when issues of justice arise and how they should
      be settled. It is interesting to consider whether any of these models of justice
      could regulate behaviour between non-human animals.

PMID- 17214317
TI  - When do we empathize?
AB  - According to a motor theory of empathy, empathy results from the automatic
      activation of emotion triggered by the observation of someone else's emotion. It
      has been found that the subjective experience of emotions and the observation of
      someone else experiencing the same emotion activate overlapping brain areas.
      These shared representations of emotions (SRE) could be the key for the
      understanding of empathy. However, if the automatic activation of SRE suffices to
      induce empathy, we would be in a permanent emotional turmoil. In contrast, it
      seems intuitively that we do not empathize all the time and that far from being
      automatic, empathy should be explained by a complex set of cognitive and
      motivational factors. I will provide here a new account of the automaticity of
      empathy, starting from a very simple question: when do we empathize? We need to
      distinguish clearly the activation of SRE and empathy. I will provide a model
      that accounts both for the automaticity of the activation of SRE and for the
      selectiveness of empathy. As Prinz (2002) says about imitation, the problem is
      not so much to account for the ubiquitous occurrence of empathy, but rather for
      its notorious non-occurrence in many situations.

PMID- 17214318
TI  - Cooperation through moral commitment.
AB  - Actions that promote fairness are sometimes consistent with the pursuit of
      individual self-interest, sometimes not. The diner who leaves a generous tip at a
      favourite local restaurant, for example, may do so partly out of a sense of
      obligation to the waiter. But we need not invoke fairness to explain the tip,
      which is, after all, a prudent investment in obtaining good service in the
      future. In contrast, narrow self-interest cannot explain why travellers might
      leave tips in restaurants located along interstate highways. Because it is
      unlikely that they will ever visit these restaurants again, their failure to tip
      cannot affect the quality of service they expect to receive in the future. So it
      is hard to escape the conclusion that concerns about fairness must be implicated
      when diners tip on the road. Of course, merely to assert the existence of a sense
      of fairness does not really explain why people often set aside concern for narrow
      self-interest. It simply raises the more fundamental question of why people have
      a sense of fairness in the first place. It is this question I will discuss.

PMID- 17214320
TI  - Pre-operative tumor assessment of patients with gastric cancer based on virtual
      endoscopy using multidetector-row computer tomography.
AB  - BACKGROUND: The possibilities and limitations of computer tomography (CT)
      examination for detecting primary gastric cancer tumors have been poorly
      understood. The aim of the present study was to evaluate the pre-operative
      assessment of gastric cancer tumors using 32-multidetector row-CT. PATIENTS AND
      METHODS: A prospective study of the pre-operative assessment of gastric cancer
      tumors using 32-multidetector row-CT was carried out. Seventy-four patients with
      adenocarcinoma of the stomach (T1 tumors, 38; T2 and T3 tumors, 36) underwent
      abdominal CTs to assess the feasibility of using MD-CT to assess primary lesions.
      RESULTS: In 35 (47%) out of the 74 patients, the primary lesions could be
      detected on 2-D images obtained by CT. In these patients, virtual endoscopic
      images of these tumors could be created. Twenty-seven advanced cancer tumors
      (75%) were assessed based on 2-D CT images and 27 larger tumors (>40 mm) (69%)
      were assessed based on 2-D CT images. Significant differences were found with
      respect to depth of tumor (p<0.0001) and tumor size (p<0.0001) between tumors
      that could or could not be assessed on MD-CT. CONCLUSION: The findings of the
      present study show that CT assessment of tumors is feasible in patients with
      advanced gastric cancer. Future studies are required to fully explore the ability
      of MD-CT to assess tumor volume in advanced gastric cancer cases and to determine
      the optimum application of this approach.

PMID- 17214319
TI  - Revisiting the role of p53 in primary and secondary glioblastomas.
AB  - Glioblastoma multiforme (GBM) develops from astrocytes and is the most aggressive
      primary cancer in humans. Invading cells grow rapidly and form their own blood
      vessels making them difficult to surgically remove or treat. GBM may develop de
      novo (primary) or through progression from a low-grade or anaplastic astrocytoma
      (secondary). Mutational inactivation of the p53 gene and presence of aberrant p53
      expression are reported in GBM, suggesting that p53 has a role in tumor
      progression. This study of seven de novo GBM and four secondary GBM patients,
      indicated that nine out of eleven (82%) had overexpression of p53. Our
      histopathological analysis showed that the expression of p53 in three out of four
      (75%) secondary GBM was confined to the nucleus and the p53 positive cells were
      randomly distributed throughout the tumor. The expression of p53 in four out of
      seven (57%) de novo GBM was cytoplasmic, diffusive, and confined to the
      perivascular region of the tumor. In two (29%) de novo samples both nuclear as
      well as cytoplasmic staining that was not confined to the perivascular area was
      observed. The results suggest that cytoplasmic p53 may contribute to the
      formation and maintenance of de novo GBM by virtue of its control of the
      vasculature of tumors. Furthermore, cytoplasmic p53 may reflect an association of
      p53 with Cullin 7, PARC, or with the sequestering partner of p53, mortalin. These
      results underscore the significance of p53 in the tumorigenesis of de novo GBM.

PMID- 17214321
TI  - Up-regulated expression of the uridine phosphorylase gene in human gastric tumors
      is correlated with a favorable prognosis.
AB  - Uridine phosphorylase (UP) is one of the enzymes involved in 5-fluorouracil (5
      FU) activation. The expression was compared in paired specimens from cancerous
      and non-cancerous regions of gastric, colon and lung cancer patients. Among 28
      paired gastric samples, 20 cases showed greater expression in tumors than in
      normal surrounding tissues and 8 cases showed equal or lower expression levels in
      tumors. All the gastric patients received 5-FU before and/or after the surgical
      resection and the prognosis of the patients, whose UP tumor expression increased,
      was relatively better than that of the patients with equal or less UP gene tumor
      expression. In contrast, most of the colon (22 cases in total) and all the lung
      cancer patients (14 in total) did not receive 5-FU and the majority of the colon
      (12 cases) and lung (10 cases) specimens showed lower expression in the cancerous
      region. The differential expression between cancerous and non-cancerous regions
      in colon and lung cancers was not linked with the prognosis. These data suggest
      that the paired expression level of the UP gene in gastric cancer is a possible
      prognostic marker for the patients who received 5-FU.

PMID- 17214322
TI  - Expression of genes for 5-FU-metabolizing enzymes and response to irinotecan plus
      5-FU-leucovorin in colorectal cancer.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) is initially catabolized by dihydropyrimidine
      dehydrogenase. Thymidylate synthase (TS) is the target enzyme of 5-FU. In
      addition, activation of 5-FU to form various nucleotides via three pathways
      requires phosphorylation by orotate phosphoribosyltransferase, thymidine
      phosphorylase and uridine phosphorylase, respectively. The aim of this study was
      to assess the predictive value of the expression of these genes in patients
      receiving irinotecan plus 5-FU/leucovorin therapy (IFL) for colorectal cancer.
      PATIENTS AND METHODS: Twenty-seven patients with metastatic, or recurrent
      colorectal cancer were studied. Enzyme gene expression was measured in primary
      tumors by the real-time reverse transcription PCR method. RESULTS: The TS mRNA
      level was significantly higher in the responders than in the non-responders
      (p=0.0409). CONCLUSION: The effect of IFL therapy may be determined by the extent
      of TS mRNA expression. It is suggested that assay of TS mRNA may be useful for
      predicting the effect of intravenous regimens such as FOLFIRI.

PMID- 17214323
TI  - Radiotherapy of classic Kaposi's sarcoma in Taiwan, an area where classic
      Kaposi's sarcoma is not prevalent.
AB  - BACKGROUND: Classic Kaposi's sarcoma (KS), a neoplastic disease of vascular
      endothelial cells of the skin, is relatively prevalent in Eastern Europe and the
      Mediterranean region and radiation is one of the standard therapies. The clinical
      presentation and treatment results of classic KS from other regions have rarely
      been reported. PATIENTS AND METHODS: Between 1994 and 2006, patients who had
      histologically confirmed KS and no immunodeficiency status due to human
      immunodeficiency virus infection or organ transplantation, and were treated with
      radiotherapy at Department of Oncology, National Taiwan University Hospital,
      Japan, were reviewed. RESULTS: A total of 17 classic KS patients, with a median
      age of 69 years, were studied over a period of 12 years. All classic KS lesions
      involved lower extremities. Radiotherapy was delivered with either a 60Co unit or
      a linear accelerator, with the most commonly prescribed treatment being 3 Gy per
      fraction to a total dose of 39 Gy. In addition, several techniques using bolus
      were adopted to improve the radiation distribution over the skin of lower
      extremities. All irradiated KS lesions responded, with a complete response rate
      of 76%. The overall survival and progression-free survival rates of the group at
      5 years were 85% and 58%, respectively. CONCLUSION: Radiation therapy for classic
      KS patients in a non-prevalent area, such as Taiwan, is safe and effective.

PMID- 17214324
TI  - Reassessment of the 1993 Osaka grading system for localized soft tissue sarcoma
      in Japan.
AB  - BACKGROUND: The Osaka system for soft-tissue sarcoma grading was proposed through
      an analysis of soft-tissue sarcoma (STS), treated from 1964 to 1989. The present
      study was conducted to evaluate the utility of the Osaka system under recent
      therapeutic regimens. PATIENTS AND METHODS: One hundred and eleven patients with
      localized STSs arising in the trunk and extremities (66 males and 45 females;
      median age 57) were selected. Histological factors, argyrophilic nucleolar
      organizer region (AgNOR) count and Ki-67 labeling index (LI) were evaluated for
      prognostic significance. RESULTS: Univariate analysis revealed that histological
      classification, mitotic count, cellularity, AgNOR count, and Ki-67 LI were
      prognostically significant for survival. Multivariate analysis revealed Ki-67 LI
      as an independent prognostic factor. The five-year survival rate for low-,
      intermediate-, and high-grade STSs in Osaka grading was 94.6%, 75.2%, and 68.4%,
      respectively. CONCLUSION: Osaka grading is a useful system for the decision
      making of therapeutic modalities for STS.

PMID- 17214325
TI  - Selection criteria for reduction hepatectomy in multiple advanced hepatocellular
      carcinoma.
AB  - BACKGROUND: Few studies have compared the prognostic impact of reduction
      hepatectomy (RH) for advanced hepatocellular carcinoma (HCC) with that of non
      surgical treatment or curative hepatectomy. PATIENTS AND METHODS: The treatment
      outcome of 30 RH patients was compared to that of two control groups: control
      group A, including 71 patients who underwent curative hepatectomy; control group
      B, including 106 patients who did not receive definitive local therapy or best
      supportive care. RESULTS: In patients with tumor extension in >50% of the liver,
      1-year survival rates for patients according to treatment (RH, control A and B)
      were 50%, 90% and 11% and 3-year survival rates were 42%, 60% and 0%,
      respectively. There was no significant difference between RH and control A, but
      there was a significant difference between RH and control B. CONCLUSION: RH could
      be recommended to patients with multiple advanced HCC extending to >50% of the
      whole liver.

PMID- 17214327
TI  - Spindle checkpoint protein hMad2 and histone H3 phosphoserine 10 mitosis marker
      in pediatric solid tumors.
AB  - Pediatric solid tumors of different histologic types are often treated with drugs
      (such as vincristine) that directly or indirectly target the mitotic spindle and
      the spindle checkpoint, leading to mitotic arrest, mitotic catastrophe and
      apoptosis. hMad2 (mitosis arrest deficient 2) expression in neuroblastoma has
      suggested utility in predicting prognosis. The present study was undertaken to
      determine hMad2 expression patterns in pediatric solid tumors, and its
      relationship to overall treatment response and short-term survival (2-years). The
      expression of hMad2 and histone H3-serine 10 phosphoprotein (mitosis marker) were
      examined using immunohistochemical staining methods in 26 pediatric solid tumors
      (six neuroblastomas, eight Wilm's, five sarcomas, four lymphomas and three
      hepatoblastomas). hMad2 expression paralleled overall histone H3 phosphoserine 10
      expression in most tumor types. Low hMad2 score tumors (0-3.5) exhibited lower
      complete response (66.67%) and a higher recurrence/progressive disease (33.33%)
      than high score tumors (4-6) (78.57% and 21.43. %), consistent with predicted
      hMad2 function and reports in adult tumors. Histone H3 serine 10 phosphoprotein
      is useful in mitosis enumeration and hMad2 expression may provide additional help
      in neuroblastoma profiling and could be useful when spindle checkpoint specific
      target drugs are used.

PMID- 17214328
TI  - Successful treatment of a patient with gastric and duodenal metastases from large
      cell carcinoma of the lung with carboplatin and gemcitabine.
AB  - A 62-year-old man with large cell carcinoma of the lung underwent a right upper
      lobectomy and four months later demonstrated a relapse in the stomach and
      duodenum. He received systemic chemotherapy consisting of carboplatin and
      gemcitabine. After the first cycle of chemotherapy, the duodenal lesion
      disappeared, however, the gastric lesion demonstrated no response. Considering
      the risk of bleeding or perforation, a partial gastroduodenal resection was
      therefore performed. Subsequently, he received adjuvant chemotherapy with the
      same regimen. He has since been doing well for 24 months after the recurrence.
      Although the prognosis for patients with gastrointestinal metastases from lung
      cancer tends to be extremely poor, treatment with chemotherapy and a
      metastasectomy have resulted in this patient, achieving a long survival.

PMID- 17214326
TI  - Post-operative combined radiation and chemotherapy with temozolomide and
      irinotecan in patients with high-grade astrocytic tumors. A phase II study with
      biomarker evaluation.
AB  - BACKGROUND: Clinical studies have shown that temozolomide (TMZ) and irinotecan
      demonstrate activity in high grade astrocytic tumors (HGAT). However, the optimal
      schedule of administration is unknown. PATIENTS AND METHODS: In the present
      study, a total of 45 HGAT patients, 38 with glioblastoma multiforme (GBM) and 7
      with anaplastic astrocytoma (AA), were treated with TMZ, 150 mg/m(2) on days 1-5,
      followed by irinotecan, 150 mg/m(2) on days 6 and 17, every 4 weeks for 6 cycles
      or until the occurrence of unacceptable toxicity or disease progression.
      Radiation therapy (60 Gy) was initiated on the first day of treatment. RESULTS:
      Twenty-two patients completed six cycles of treatment. Most frequently recorded
      side-effects included neutropenia (37%), nausea/vomiting (66%), diarrhea (31%)
      and infection (44%). Five episodes of vaso-occlusive disease, all of them fatal,
      were observed. After a median follow-up of 49.8 months, median progression-free
      survival for patients with GBM was 7.7 months, while median overall survival was
      12.8 months. There were six long-term survivors, three of them with GBM. Two out
      of the five biomarkers studied, epidermal growth factor receptor (EGFR) and
      vascular endothelial growth factor-C (VEGF-C), were found to be overexpressed in
      74% of the tumors, however they had no predictive value for progression-free or
      overall survival. CONCLUSION: The combination of TMZ and irinotecan, as
      administered in this study, was accompanied by high rates of toxicity, especially
      myelotoxicity and infection. Further development of this regimen in the treatment
      of HGAT is not recommended.

PMID- 17214329
TI  - Weekly administration of irinotecan (CPT-11) plus cisplatin for non-small cell
      lung cancer.
AB  - BACKGROUND: Weekly administration of irinotecan plus cisplatin was evaluated for
      untreated patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:
      Sixty mg/m(2) of irinotecan plus 30 mg/m(2) of cisplatin were administered on
      days 1, 8 and 15 every 4 weeks. Patients with no evidence of disease progression
      were treated with at least two cycles (8 weeks). Of the 39 patients, 29 were
      provided an antidiarrheal program consisting of sodium bicarbonate and magnesium
      oxide. RESULTS: There were 13 partial responses and an overall response rate of
      33.3% [95% CI: 20%-50%]. The median time to progression and survival were 64 days
      and 12.8 months, respectively. Grade 4 neutropenia occurred in 15.4% of the
      patients, and Grade 3 and 4 diarrhea was observed in 12.8% and 2.6%,
      respectively. The incidence of leukopenia of grade 3-4 was significantly lower in
      patients provided with the antidiarrheal program due to lack of decrease in the
      lymphocyte count. CONCLUSION: This phase II study indicated that weekly
      irinotecan plus cisplatin administration was a promising treatment for untreated
      NSCLC.

PMID- 17214330
TI  - Positron emission tomography with F-18 fluorodeoxyglucose in evaluating
      colorectal hepatic metastasis down-staged by chemotherapy.
AB  - BACKGROUND: The efficacy of positron emission tomography with 18F fluoro-2-deoxy
      D-glucose (FDG-PET) is obscure in evaluating viability or the extent of
      colorectal hepatic metastasis (CHM), down-staged by chemotherapy. PATIENTS AND
      METHODS: A retrospective lesion-by-lesion analysis was performed for seven
      consecutive patients, who had received rescue hepatectomy for initially
      unresectable CHM, in order to evaluate the correlation between results of imaging
      modalities and the corresponding pathology. RESULTS: The sensitivity and positive
      predictive value of the conventional modalities (CT and MRI) were 92% and 42%,
      respectively, while the sensitivity, specificity, positive predictive value and
      negative predictive value of FDG-PET were 58%, 100%, 100% and 75% respectively.
      The sensitivity of FDG-PET was 100% in evaluating the viability of tumors >2 cm,
      however, this fell to 17% in tumors <2 cm. CONCLUSION: FDG-PET is effective in
      assessing the viability of tumors >2 cm, but not those <2 cm, in patients with
      CHM down-staged by chemotherapy.

PMID- 17214331
TI  - Elevated levels of circulating cell-free DNA in the blood of patients with
      hepatitis C virus-associated hepatocellular carcinoma.
AB  - BACKGROUND: Circulating cell-free DNA is present in increased amounts in the
      blood of patients with one of several forms of cancer. MATERIALS AND METHODS: A
      real-time PCR assay with glutathione S-transferase pi (GSTP1) gene was used to
      measure cell-free DNA levels in the sera of 52 patients with hepatocellular
      carcinoma (HCC) associated with hepatitis C virus (HCV), which included 30 HCV
      carriers without known HCC and 16 HCV-negative non-cancer patients (controls).
      RESULTS: Cell-free DNA levels were significantly higher in the sera from HCC
      patients than in the sera from HCV carriers or the control subjects. Cell-free
      DNA levels were associated with the degree of tumor differentiation and size but
      not patient age, gender, TNM stage or levels of alpha-fetoprotein (AFP) or
      protein induced by vitamin K absence (PIVKA-II). The cell-free DNA assay had a
      sensitivity of 69.2% and a specificity of 93.3% in discriminating HCC and HCV
      carriers at the optimal cut-off value of 73.0 ng/ml, with an area of 0.90 (95%
      CI, 0.83-0.96) under the receiver operating characteristic curve. The
      discriminative power of cell-free DNA was superior to that of AFP or PIVKA-II.
      CONCLUSION: Our results showed that levels of circulating cell-free DNA are
      significantly increased in sera of patients with HCV-associated HCC, suggesting
      that circulating cell-free DNA may be a good biomarker specific for HCV
      associated HCC.

PMID- 17214332
TI  - Serum mesothelin in epithelial ovarian carcinoma: a new screening marker and
      prognostic factor.
AB  - The aim of this study was to determine the relationship between mesothelin and
      clinical pathological characteristics and whether mesothelin can be used as a
      biomarker for the detection and prognosis of epithelial ovarian carcinoma, or
      not. PATIENTS AND METHODS: Pre-operative mesothelin and CA125 levels from normal
      populations, patients with benign ovarian tumors and patients with ovarian
      carcinomas were measured. The histopathological characteristics and serum
      meosthelin, and CA125 levels influencing clinical outcome were evaluated
      comparatively. RESULTS: Mesothelin levels were higher in cancer patients than in
      those with benign ovarian tumors or in normal populations. Mesothelin, also
      significantly increased from early to advanced stages. Elevated mesothelin before
      therapy and advanced stage, revealed poorer overall survival (OS) for cancer
      patients. Elevated mesothelin before therapy also revealed poorer OS in cancer
      patients with optimal debulking surgery and in advanced-stage cancer patients.
      CONCLUSION: Mesothelin might be a new tumor marker for the differential diagnosis
      of epithelial ovarian carcinoma and a prognostic factorfor the outcome of
      epithelial ovarian carcinoma patients.

PMID- 17214333
TI  - Oral contraceptives are not an independent risk factor for cervical
      intraepithelial neoplasia or high-risk human papillomavirus infections.
AB  - BACKGROUND: Oral contraception (OC) has been proclaimed by the IARC as a risk
      factor of cervical cancer (CC), on prolonged use by high-risk human
      papillomavirus (HPV) positive women. However, the available data are far from
      complete, and more evidence is necessary on the potential confounding effects of
      sexual behavior and HPV infection. The aim of the present was study to analyse
      the risk estimates for OC users in order to develop several intermediate end
      point markers in cervical carcinogenesis. PATIENTS AND METHODS: A cohort of 3,187
      women, enrolled in a multi-center screening trial in three New Independent States
      (NIS) of the former Soviet Union (the NIS Cohort Study), was stratified into
      three groups according to their contraception modes: i) non-users of
      contraception, ii) non-OC users and iii) OC users. These groups were analysed
      forpredictors of three outcome measures: a) exposure to HR-HPV; b) progression to
      high-grade cervical intraepithelial neoplasia (CIN2/3 and HSIL); and c)
      persistence/clearance of HR-HPV and cytological abnormalities during a
      prospective follow-up. RESULTS: All three groups had an identical prevalence of
      HR-HPV (HCII and PCR), Pap smear abnormalities and CIN histology, but differed
      significantly (p=0.0001) with regard to all key variables of sexual behaviour,
      known as risk factors for CC. Predictors of HR-HPV, CIN2/3 and HSIL were
      different in the three groups, reflecting these different sexual preferences. Use
      of OC was not a significant predictor of CIN2/3 or HSIL in HPV-positive or HPV
      negative women. Outcomes of cervical disease and HR-HPV infection were unrelated
      to contraception. In a multivariate regression model mode of contraception was of
      no predictive value for either HR-HPV or high-grade CIN. CONCLUSION: Sexual
      behaviour is different among OC users, non-OC users and in nonusers of
      contraception; these risk factors predispose women to HR-HPV, high-grade CIN, and
      determine the outcome of their cervical disease/HR-HPV infection. The use of OC
      is not an independent risk factor for any of these intermediate end-point markers
      of cervical carcinogenesis. Failure to record these epidemiological data
      inevitably leads to erroneous conclusions about the role of OC as an independent
      risk factor of cervical cancer.

PMID- 17214334
TI  - Squamous cell carcinoma of the nasopharynx metastasising to rectum: first case
      report and literature review.
AB  - Squamous cell carcinoma (SCC) of the nasopharynx is amongst the most common head
      and neck cancers. However, distant metastases are clinically underdiagnosed, as
      demonstrated by significantly higher metastatic rates in autopsy studies,
      compared to clinical studies. The incidence of metastases continues to rise with
      improvements in diagnostic imaging, locoregional control and survival. Metastases
      to the colorectum are extremely rare. This is the first case of nasopharyngeal
      SCC, metastasising to the rectum. A brief review of the literature is performed,
      with discussion on the screening, diagnosis and treatment of non-primary /
      metastatic tumours of the colorectum, from SCC and other primary tumours.

PMID- 17214335
TI  - Biochemical and clinical approaches in evaluating the prognosis of colon cancer.
AB  - BACKGROUND: Colorectal adenocarcinoma is a common malignant neoplasm in the
      Western world. To achieve optimal treatment results, the risk estimation of
      recurrence should be as accurate as possible. MATERIALS AND METHODS: Tissue
      material from tumour and normal mucosa was taken from six patients and was
      analysed to screen aberrantly expressed genes using cDNA microarray. Selected up
      regulated genes were chosen for further analysis by immunohistochemistry. For
      this purpose a tissue array material of 114 colorectal cancer patients was
      obtained. In addition to the routinely used proliferation marker Ki-67, the
      analysed proteins included securin and CDC25B. RESULTS: Processes such as
      cellular defense, cell structure, motility and cell division were found to be
      notably represented among the most deregulated genes. A significant portion of
      the overexpressed genes included those functioning in the cell cycle.
      Immunohistochemical stainings of securin and CDC25B showed a consistent
      expression pattern with that of cDNA microarray analysis. There was no
      statistical association between the studied proliferation markers and survival.
      Instead, there was a significant association between the Dukes' class and the
      histological grade (p=0.04), but not between histological grade and survival. The
      survival of Dukes' B patients was significantly poorer if no regional lymph nodes
      were studied compared with the Dukes' B patients with even a single lymph node
      was studied (p=0.04, hazard ratio 2.7). CONCLUSION: Tumour stage is superior in
      estimating the prognosis of patients with colonic cancer compared with the
      grading of cell cycle regulators or histological grade of the cancer. The study
      of regional lymph nodes is essential to identify the patients who would benefit
      from adjuvant chemotherapy.

PMID- 17214336
TI  - Thymidine kinase 1 in serum predicts increased risk of distant or loco-regional
      recurrence following surgery in patients with early breast cancer.
AB  - BACKGROUND: The prognostic value of the concentration of serum thymidine kinase 1
      (S-TK1) with regard to recurrence in low risk breast cancer patients, 3 months
      after surgery was evaluated. PATIENTS AND METHODS: The concentration of S-TK1 in
      serum was determined in 120 breast cancer patients at the time of surgery and in
      67 patients 3 months after surgery, by anti-TK1 chicken IgY antibody, using a dot
      blot immuno-assay. The S-TK1 concentration was compared with the serological
      activity of thymidine kinase (STK) and of carbohydrate antigen (CA 15-3).
      RESULTS: A statistically significant trend (unadjusted) was found for recurrence
      (distant or loco-regional) in patients with a higher S-TK1 concentration, as
      compared with patients with a lower S-TK1 concentration. A multivariate analysis
      gave the same results. The hazard rate ratio for developing distant and/or loco
      regional recurrence in patients with a higher S-TK1 concentration was about six
      to seven times higher than in patients with a lower S-TK1 concentration.
      CONCLUSION: Our results indicate that the S-TK1 concentration is higher in
      patients developing distant and/or loco-regional recurrence 3 months post
      surgery.

PMID- 17214337
TI  - Telomerase activation--one step on the road to carcinoma of the gall bladder.
AB  - BACKGROUND: As information on telomeres and telomerase dynamics in the regulation
      of cell cycle events accumulates, new opportunities for application to
      gerontology and cancer therapy are emerging. The aim of this study was to detect
      the telomerase activity (hTERT protein) in the biopsy specimens of human
      carcinoma of the gall bladder. PATIENTS AND METHODS: Thirty cases each of
      carcinoma of the gall bladder and cholelithiasis (controls) were analysed.
      Immunohistochemistry was employed using mouse monoclonal antibody against hTERT
      protein and by taking human tonsil and testicular tissue as positive controls.
      RESULTS: Seventeen cases (56.66%) of carcinoma of the gall bladder and 2 cases
      (6.66%) of cholelithiasis were strongly positive for telomerase. The difference
      was statistically significant (p<0.001). Six cases (20%) of gall bladder
      carcinoma and one case (3.33%) of cholelithiasis were weakly positive. The
      difference was highly statistically significant (p<0.001). Telomerase activity
      was mainly concentrated in poorly-differentiated adenocarcinomas (83.33%) and
      increased expression was noted in advanced stages. CONCLUSION: The presence of
      telomerase may serve as a molecular marker for the diagnosis of gall bladder
      carcinoma and may have prognostic and therapeutic implications in the treatment
      of patients in the future.

PMID- 17214338
TI  - Basal cell carcinoma of the nose requiring amputation arising after irradiation
      for childhood hemangioma.
AB  - A 49-year-old female, who had undergone irradiation at six years of age as a
      treatment for a cutaneous nasal hemangioma, developed later a devastating basal
      cell carcinoma requiring sub-amputation of the nose and subsequent reconstruction
      with a pre-expanded forehead flap. Basal cell carcinomas are now frequently
      reported as late sequelae of previous low-dose irradiations after 10-20 years,
      and patients should be aware of this possible evolution.

PMID- 17214339
TI  - Severe skin reaction in a patient with gastrointestinal stromal tumor treated
      with imatinib mesylate.
AB  - Imatinib mesylate is a selective protein kinase inhibitor, highly active in
      patients with chronic myeloid leukemia (CML) and gastrointestinal stromal tumors
      (GISTs). Cutaneous toxicity, a well-recognized, dose-related side-effect of
      imatinib mesylate, has been reported in 18 to 69% of patients with GIST treated
      with doses ranging from 400 to 800 mg once a day. In this case-report a severe
      skin reaction observed in a patient with GIST treated with imatinib mesylate, in
      an adjuvant setting and whose severity led to definitive drug discontinuation, is
      described. Therapeutic management and clinical course are illustrated.

PMID- 17214340
TI  - Secondary breast angiosarcoma: lethal response to anti-angiogenic therapy with
      paclitaxel chemotherapy. A case report.
AB  - Angiosarcoma of the breast is a malignant tumour of vascular endothelial cells.
      It is a rare and difficult tumour to treat. The authors report a case of
      cutaneous radiation-associated angiosarcoma treated with paclitaxel chemotherapy.
      A few days after drug administration, bleeding of skin lesions was observed and
      the patient died.

PMID- 17214341
TI  - The value of sequential serum measurements of gelatinases and tissue inhibitors
      during chemotherapy in ovarian cancer.
AB  - BACKGROUND: Gelatinases and tissue inhibitors of metalloproteinases (TIMPs) are
      involved in tumour invasion and metastasis. High pre-operative TIMP-1 serum
      values have been previously found to correlate to aggressive features in ovarian
      cancer patients. This study has examined the clinical value of sequential serum
      measurements of gelatinases and TIMPs during ovarian cancer treatment. PATIENTS
      AND METHODS: Serum gelatinase and TIMP values were measured in 48 patients
      receiving cytotoxic chemotherapy for ovarian cancer. The serum values were
      analysed by enzyme-linked immunosorbent assay (ELISA) in the third and sixth
      chemotherapy cycles, and compared to the treatment response. RESULTS: Increased
      MMP-9 (matrix metalloproteinase-9), TIMP-2 and MMP-2 mean serum values were
      observed in optimally operated patients with a complete response to treatment,
      compared to those with a partial response. No significant differences were found
      in the change of circulating TIMP-1 values in the different chemotherapy response
      groups. CONCLUSION: Measuring the serum values of gelatinases or TIMP-2
      sequentially during chemotherapy might be beneficial for response evaluation in
      optimally operated patients, whereas the serum TIMP-1 values might not contribute
      to an evaluation of the treatment response.

PMID- 17214342
TI  - Hepatic metastases of colorectal cancer: locoregional intra-arterial treatment.
AB  - A radical resection alone of colorectal hepatic metastases is possible in only 10
      20% of the patients but, when resection and ablation are combined, the rate of
      radicalism can improve. A regional hepatic intra-arterial chemotherapy infusion
      (HAI) has been introduced in the clinical practice, as a possible alternative
      approach to systemic chemotherapy. Nevertheless, the introduction of new systemic
      therapies with monoclonal antibodies, combined to irinotecan or oxaliplatin,
      recently improved response rates and overall survival ia these patients. Aiming
      to evaluate a possible influence of HAI in these new treatments, the most
      important studies underlining the evolution of intrahepatic administration in
      recent years are reviewed.

PMID- 17214343
TI  - Ovarian cancer screening.
AB  - PURPOSE: This review presents the current knowledge on ovarian cancer screening
      (OCS) together with a cumulative evaluation of the efficacy across diverse
      screening approaches based on up-to-date results. MATERIALS AND METHODS: An
      electronic literature search was conducted targeting reports on the effectiveness
      of the various screening strategies. RESULTS: Twenty-two prospective studies, 18
      cohorts and 4 randomised control trials (RCTs) were retrieved. Where possible,
      sensitivity, specificity and predictive values, as well as the number needed to
      treat for each cancer (NNT) and each stage I disease [NNT (I)] detected are
      reported. CONCLUSION: The multimodal approach that incorporates CA125 as a
      primary and ultrasound as a secondary test appears to be superior to other
      strategies. However, the conclusive end-point that would provide the acceptable
      level of evidence for the introduction of screening should be a reduction in
      mortality. Up-to-date, there is no such evidence to justify this.

PMID- 17214344
TI  - Parathyroid cancer: etiology, clinical presentation and treatment.
AB  - Parathyroid carcinoma (PC) is an uncommon finding, accounting for only 1-2% of
      patients with primary hyperparathyroidism (HPT), but a relatively higher
      incidence has been reported in Italy and Japan. The etiology of the tumour
      remains unclear, but molecular analysis studies have hypothesised the involvement
      of mutations of several genes in the pathogenesis of PC, including the oncogene
      cyclin Dl or PRADI located at the chromosome 13, the retinoblastoma and the p53
      tumour suppressor gene. The clinical presentation of patients with PC is mainly
      related to the increased secretion of PTH rather than to the tumour burden. The
      pre-operative diagnosis of malignancy is very difficult to obtain, and, thus,
      intra-operative recognition of PC is mandatory. However, reliable signs of
      malignancy are rarely detectable. Probably, only vascular invasion, that
      correlates with tumour recurrence and metastases, should be considered useful in
      confirming malignancy, although both Ki-67 and Cyclin D1 have been recently used
      to aid in the definitive diagnosis. The en bloc resection of the tumour, together
      with ipsilateral thyroid lobe and adjacent structures, only if involved, avoiding
      any capsular rupture of the mass, represents the gold standard of surgical
      treatment of patients. Although the PC has traditionally been considered as a
      radioresistant tumour, there are some retrospective data holding a possible
      benefit from post-operative irradiation. No cytotoxic regimen with proven
      efficacy is currently available for patients with PC, but since hypercalcemia is
      ultimately the most frequent cause of death, several studies have suggested the
      usefulness of bisphosphonates (i.e., clodronate, pamidronate and zoledronate),
      calcitonin, and calcimimetic agents (i.e., cinacalcet) in patients with PC and
      severe hypercalcemia. In conclusion, PC is a rare malignancy and the NCDB survey
      reports an overall five- and ten-year survival rate of 85% and 49%, respectively.
      However, it is very difficult to predict the clinical behaviour of patients with
      PC and probably the ultimate prognosis depends on successful resection of the
      tumour at the initial surgery.

PMID- 17214345
TI  - Adjuvant chemotherapy for colon cancer.
AB  - Surgery remains the only curative therapy for colon cancer. However, several
      studies during the last years have proved that systemic chemotherapy in the
      adjuvant setting definitely improves the curative rate for those patients with
      localized colon cancer. The combination of 5-fluorouracil (5-FU) and leukovorin
      (LV) remained the reference treatment for over a decade. However, oxaliplatin
      based chemotherapy has emerged as the new standard of care in adjuvant treatment
      of stage III colon cancer. The role of adjuvant therapy in stage II cancers
      remains controversial and its routine use is recommended only in high risk
      patients. This review focuses on the efficacy, safety and toxicity of several
      drugs used in the adjuvant treatment of colon cancer and on clinical issues, such
      as the timing for initiation of chemotherapy, its duration and treatment of
      special patient subgroups, such as stage II or elderly patients.

PMID- 17214346
TI  - Carcinosarcomas--a retrospective analysis of 21 patients.
AB  - BACKGROUND: Carcinosarcomas (CS) are mixed epithelial and stromal tumours with
      both components being malignant. Twenty-one patients with carcinosarcomas who
      were treated at the University of Saarland, Germany, are presented. PATIENTS AND
      METHODS: The hospital records of all patients were reviewed. RESULTS: The mean
      age range for homologue CS (homCS) was 60.7 years and for heterologue CS (hetCS)
      68.4 years. Post-menopausal bleeding and abdominal pain were the main symptoms.
      Treatment modalities included surgery, adjuvant radiation therapy and various
      chemotherapy regimens. The median follow-up time was 17.6 months (homCS) and 31.1
      months (hetCS). The 1-year survival rate was 55.6% (hetCS 58.3%) and the 5-year
      survival rate was 11.1% (hetCS 8.3%). CONCLUSION: Carcinosarcoma is a uterine
      sarcoma with a poor prognosis. Treatment includes surgery and adjuvant
      chemotherapy, whereas radiotherapy does not necessarily lead to a benefit.
      Treatment with trastuzumab might be a new approach in the therapy of HER-2/neu
      positive CS.

PMID- 17214347
TI  - Predictive and prognostic factors in small cell lung carcinoma (SCLC)--analysis
      from routine clinical practice.
AB  - BACKGROUND: Prognostic and predictive factors of routine clinical practice among
      patients with small cell lung carcinoma (SCLC) were evaluated. PATIENTS AND
      METHODS: Data from 106 patients with SCLC treated by first-line adriamycin,
      cyclophosphamide and etoposide (ACE) chemotherapy were analyzed. Multivariate
      analysis was performed. RESULTS: The median overall survival (mOS) of patients
      was 9.36 months with mOS of 31%, 8% and 3% after 1, 2 and 5 years, respectively.
      Using multivariate analysis ECOG performance status (p =0.008) and white blood
      count (WBC) (p=0.022) were independent prognostic factors for mOS. With both,
      three groups of outcome (good, intermediate, poor) resulting in mOS of 15.8
      months, 6.87 months and 3.35 months (p<0.0001) could be established,
      respectively. The absence of brain metastases (p=0.002), dose reduction (p=0.002)
      and LDH value (p=0.017) were independent predictive markers. Additionally, female
      gender was predictive (p=0.025) for complete response (CR). CONCLUSION: Patients
      with a poor prediction profil might not benefit from ACE chemotherapy. As a
      consequence, prognostic/predictive factors should be included as stratification
      criteria in prospective clinical studies.

PMID- 17214348
TI  - Expression of vascular endothelial growth factor in malignant mesothelioma.
AB  - Malignant mesothelioma is the most common primary pleural neoplasm. Angiogenesis
      is an important component of a variety of pathological processes, including
      carcinogenesis and tumor metastases. Vascular endothelial growth factor (VEGF) is
      the most potent known endothelial, cell specific mitogen. The authors assessed
      the relation between VEGF expression and clinicopathological variables or overall
      survival, in malignant mesothelioma. We studied 37 patients with malignant
      pleural mesothelioma and found that 36 out of 37 (97.3%) malignant mesothelioma
      samples were stained positively for VEGF. An increased expression of VEGF was
      observed in the epithelioid type compared with the other histological types of
      malignant mesothelioma, including the biphasic and sarcomatoid types. No
      statistically significant association was observed between VEGF expression and
      gender, age, or clinical stage. Furthermore, the expression of VEGF did not
      impact on the survival of patients with malignant mesothelioma. Although VEGF
      expression might be important for tumor development and maintenance, it was not
      identified as a prognostic factor in malignant mesothelioma.

PMID- 17214349
TI  - Angiosarcoma of the heart: case report and review of the literature.
AB  - BACKGROUND: Primary angiosarcoma of the heart is an extremely rare malignant
      disease. PATIENTS AND METHODS: A 32-year-old female with primary angiosarcoma of
      the heart at an advanced stage with lung and bone metastases is presented. The
      tumor showed extensive expression of c-erb-B2 and a moderate expression of c-kit.
      Chemotherapy (cisplatin, epirubicin and ifosfamide) was administered. Herceptin
      as well as glivec were added to the above combination. RESULTS: There was a good
      partial response and the lung deposits almost disappeared. The duration of
      response was 6 months. CONCLUSION: This case of angiosarcoma of the heart is
      presented because of the extreme rarity of this disease, and its responsiveness
      to chemotherapy in combination with imatinib and herceptin.

PMID- 17214350
TI  - Determination of cervicovaginal microorganisms in women with abnormal cervical
      cytology: the role of Ureaplasma urealyticum.
AB  - OBJECTIVE: To evaluate the existence of an association between cervicovaginal
      infections and precancerous lesions of the uterine cervix, through determination
      of prevalent cervicovaginal micro-organisms, alone and in association with human
      papillomavirus (HPV), in patients with abnormal and normal vaginal cytology.
      PATIENTS AND METHODS: Patients with abnormal vaginal cytology were divided into
      three study groups according to cytological findings: ASC-US, L-SIL and H-SIL.
      All patients underwent colposcopic examination and exoendocervical and vaginal
      sampling for microbiological and molecular analysis for detection of HPV-DNA,
      Ureaplasma urealyticum, Chlamydia trachomatis, Trichomonas vaginalis, mycetes and
      common bacteria. Results were compared with the patient group asymptomatic for
      cervicovaginal inflammation with negative vaginal cytology and colposcopy.
      RESULTS: A high association between Ureaplasma urealyticum infection and the
      grade of cytological cervical lesion (27% for ASC-US, 35% for L-SIL and 45% for H
      SIL) was found. Furthermore, 19% of the control group samplings were positive for
      Ureaplasma urealyticum, significantly less than that observed in the positive
      cytology groups. An interesting association of HPV with Ureaplasma urealyticum in
      patients with H-SIL vaginal cytology (83%), much higher than that observed in
      patients with slightly abnormal or normal vaginal cytology (56% for ASC-US, 49%
      for L-SIL, 40% for normal cytology) was also identified. In contrast, the
      association between Papillomavirus and multiple microorganisms seemed to decrease
      with the level of cellular dysplasia in 30% of controls, 33% of ASC-US, 32% of L
      SIL and 17% of H-SIL. CONCLUSION: The presence of a high Ureaplasma urealyticum
      level seems to be a cofactor of HPV infection, a necessary cause of precancerous
      lesions of the uterine cervix. The presence of Ureaplasma urealyticum may play a
      role both in initiating viral cellular anomalies and in viral persistence. It can
      be hypothesized that these initial processes are helped by a state of cervical
      inflammation, also supported by multiple microorganisms. It would, thus, be
      suggested for all patients who present with an abnormal PAP test to undergo a
      cervicovaginal microbiological examination to detect potentially pathogenic
      microbes for correct diagnosis and treatment, as well as a more complete follow
      up of cervical cytological lesions.

PMID- 17214351
TI  - Salvage chemotherapy with carboplatin and paclitaxel for cisplatin-resistant
      thymic carcinoma--three cases.
AB  - The optimal chemotherapeutic regimen for thymic carcinoma remains uncertain and
      the utility of salvage therapy has also not been reported. Three cases of
      unresectable and locally advanced thymic carcinoma, resistant to prior
      chemotherapy with cisplatin are reported. These patients were treated with
      carboplatin and paclitaxel chemotherapy, as salvage chemotherapy. Although
      concomitant thoracic radiotherapy was performed in one patient, two showed a
      partial response and the other showed a minor response after carboplatin and
      paclitaxel chemotherapy. Thymic carcinoma is sensitive to platinum-based
      chemotherapy and paclitaxel appears to have significant activity against thymic
      carcinoma.

PMID- 17214352
TI  - Liposarcoma of the oral cavity--case reports of the pleomorphic and the
      dedifferentiated variants and a review of the literature.
AB  - Liposarcoma is one of the commonest soft-tissue sarcomas, but very rare in the
      oral cavity. We present two cases of liposarcoma of the oral cavity, together
      with the related clinical, histopathological and immunohistochemical findings:
      one affecting the cheek of a 62-year-old man and the other the gingival maxillary
      tuber of a 41-year-old woman. At histological examination a diagnosis of
      liposarcoma was made in both cases. In the first case, immunohistochemical
      analysis revealed intense positivity for p53, MIB-1, MDM2, and focal positivity
      for S100 protein and CD34, but was negative for alpharsmooth muscle actin, desmin
      and CD68. The second case it was intensely positive for p53, MIB-1, S-100, and
      focal positive for MDM2, but negative for alpha smooth muscle actin, CD34, CD68
      and desmin. Histological examination and immunohistochemical profiles in the
      first case were consistent with pleomorphic liposarcoma, whilst that in the
      second case with dedifferentiated liposarcoma. Both patients were subjected to
      surgical treatment with wide surgical margins, without adjuvant radio- or
      chemotherapy. The first case was lost at follow-up one year after surgery, while
      the second case has not undergone relapse after seven years. We discuss
      differential diagnosis, examining the histopathological and immunohistochemical
      features that are potentially useful for distinguishing this tumor from other
      malignant adipose tissue tumors.

PMID- 17214353
TI  - Two cases of complete response after imatinib mesylate treatment of advanced
      GIST.
AB  - BACKGROUND: Imatinib mesylate has undoubted efficacy in the treatment of advanced
      gastrointestinal stromal tumors (GISTs), but complete responses have only been
      reported rarely. CASE REPORT: A 47-year-old man with liver metastasis from GIST
      achieved a complete response after 7 months of treatment with imatinib and a 47
      year old woman with local relapse of GIST on the stomach after gastrectomy,
      showed complete remission, 9 months after treatment with imatinib. CONCLUSION:
      Although the response rate is high in patients with advanced GIST treated with
      imatinib mesylate, complete responses remain rare. Several issues concerning its
      optimal administration need to be clarified, in order to improve its efficacy.

PMID- 17214354
TI  - Expression of Ki-67, cyclin D1 and apoptosis markers correlated with survival in
      prostate cancer patients treated by radical prostatectomy.
AB  - OBJECTIVE: The study was designed to analyse the prognostic value of
      proliferation markers Ki-67 and cyclin D1 and apoptosis in prostate cancer (PC)
      patients treated by radical prostatectomy. PATIENTS AND METHODS: Two hundred and
      eleven patients treated by radical prostatectomy for localised prostate cancer
      were clinically followed up for a mean of 7.3 years. The primary
      histopathological specimens were re-analysed to ensure uniform histoplthological
      grading and pT classification. A tissue microarray construction (TMA) was used in
      immunohistochemisty to assess the expression of Ki-67, cyclin D1 and the
      apoptosis marker Tag. The results were analysed with light microscopy and the
      findings were compared to standard histology, pT and clinical follow-up data.
      RESULTS: The co-expression of Ki-67 and cyclin Dl (p=0.05) was common. High
      fraction of Ki-67 positive cells and a high fraction of apoptotic cells were
      often present in same tumours (p=0.05). High apoptotic rate was related to
      positive surgical margin status (p=0.047). Low expression of Ki-67 was related to
      a low Gleason score (p<0.001), an absence of either capsule penetration (p =
      0.029) or perineural invasion (p=0.004). High expression of cyclin Dl was related
      to perineural growth (p=0.039). Prostate specific antigen (PSA) recurrence-free
      survival (RFS) was predicted by Gleason grade (p<0.001) and capsule invasion
      (p=0.006). High expression of Ki-67 (p=0.03), as well as high apoptotic rate
      (p=0.04) were related to a high risk of cancer death. In multivariate analysis
      the seminal vesicle invasion was the only independent predictor of cancer death
      (p = 0.01). CONCLUSION: The expression of Ki-67, cyclin D1 and a high apoptotic
      rate are related to a malignant phenotype in prostate cancer, but their
      prognostic value is inferior to standard histological prognostic factors.

PMID- 17214355
TI  - Survival markers related to bone metastases in prostate cancer.
AB  - Prognostic value of a bone resorption marker, tartrate-resistant acid phosphatase
      isoform 5b (TRACP 5b), and two matrix metalloproteinases (MMP-2 and MMP-9) was
      compared with the standard clinical analyses of total alkaline phosphatase (tALP)
      and prostate-specific antigen (PSA), in prostate cancer (PC) patients with (BM+)
      or without (BM-) bone metastases. Diagnostic accuracy evaluation showed the
      highest area under the curve for tALP (AUC=0.98), followed by PSA (AUC=0.87),
      TRACP 5b (AUC=0.82), MMP-9 (AUC=0.62) and MMP-2 (AUC=0.53). Significantly shorter
      survival was observed for patients with tALP (p<0.001), TRACP 5b (p=0.002) and
      PSA (p<0.001) levels, above the determined cut-off values compared with lower
      marker levels. In multivariate Cox regression analysis, only tALP and PSA, in
      addition to Gleason score were independent prognostic factors for survival. Of
      the three novel markers tested, only TRACP 5b proved to be predictive of survival
      in PC with bone metastases. MMP-2 and -9 are thus not recommended for further
      studies in this context.

PMID- 17214356
TI  - The CHEK2 1100delC variant in Swedish colorectal cancer.
AB  - BACKGROUND: The cell cycle checkpoint kinase 2 (CHEK2) 1100delC variant has
      recently been identified at high frequency in families with both breast and
      colorectal cancer, suggesting the possible role of this variant in colorectal
      cancer predisposition. PATIENTS AND METHODS: To evaluate the role of CHEK2
      ll00delC among Swedish colorectal cancer patients, the variant frequency was
      determined in 174 selected familial cases, 644 unselected cases and 760 controls,
      as well as in l8 families used in the genome-wide linkage analysis, where weak
      linkage was seen for the region harboring the CHEK2 gene. RESULTS: CHEK2 l100delC
      was found in 1.15% of familial and in 0.93% of unselected cases, compared to
      0.66% of controls, showing no significant difference between groups. One out of
      45 familial cases with a family history of breast cancer was shown to be a
      carrier. The variant was not identified in the 18 families included in the
      linkage analysis. CONCLUSION: The CHEK2 1100delC was not significantly increased
      in Swedish colorectal cancer patients, however, in order to determine the role of
      the variant in colorectal cancer families with the history of breast cancer a
      larger sample size is needed.

PMID- 17214357
TI  - Lack of the type III epidermal growth factor receptor mutation in colorectal
      cancer.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) analysis by traditional
      immunohistochemistry does not provide clinicians with a reliable tool for the
      selection of patients to EGFR-targeted treatment in colorectal cancer (CRC).
      Alternative methods and further understanding of the EGFR signaling network are
      being investigated and mutations in the EGFR gene have been identified. The type
      III epidermal growth factor receptor, a tumour-specific, ligand independent,
      constitutively activated form of EGFR, might contribute to the malignant
      phenotype in CRC and may be a potential target for anticancer therapy. The aim of
      the present study was to investigate the presence of EGFRvIII in CRC by PCR and
      protein analysis. MATERIALS AND METHODS: The study included 79 colorectal cancer
      patients for PCR analysis and 50 patients for protein analysis by Western blots,
      in two different laboratories. RESULTS: No type III mutations were detected in
      our material. CONCLUSION: The EGFRvIII mutations are rare in colorectal
      adenocarcinomas and overall probability does not appear to contribute to the
      malignant phenotype of this disease.

PMID- 17214358
TI  - Reliability of the reported size of removed colorectal polyps.
AB  - BACKGROUND: The size of colorectal polyps is important in the clinical management
      of these lesions. AIM: To audit the accuracy in calculating the size of "polyps"
      by various specialists. MATERIALS AND METHODS: Eighteen pathologists and four
      surgeons measured, with a conventional millimetre ruler, the largest diameter of
      12 polyp phantoms. The results of two independent measurements (two weeks apart)
      were compared with the gold standard-size assessed at The Royal Institute of
      Technology, Sweden. RESULTS: Thirty-one percent (83/264-trial 1) and 33% (88/264
      trial 2) of the measurements underestimated or overestimated the gold standard
      size by >1 mm. Of the 22 experienced participants, 95% (21/22-trial 1) and 91%
      (20/22-trial 2) misjudged by >1 mm the size of one or more polyps. Values given
      by 13 participants (4.9%) in trial 1 and by 15 participants (5.7%) in trial 2,
      differed by > or = +/-4 mm from the gold standard size. In addition, a big
      difference between the highest and the lowest values was recorded in some polyps
      (up to 11.4 mm). Those disparate values were regarded as a human error in reading
      the scale on the ruler. CONCLUSION: Using a conventional ruler (the tool of
      pathologists worldwide) unacceptably high intra-observer and inter-observer
      variations in assessing the size of polyp-phantoms was found. The volume and the
      shape of devices, as well as human error in reading the scale of the ruler were
      confounding factors in size assessment. In praxis, the size is crucial in the
      management of colorectal polyps. Considering the clinical implications of the
      results obtained, the possibility of developing a method that will allow
      assessment of the true size of removed clinical polyps is being explored.

PMID- 17214359
TI  - hTERT mRNA expression is associated with a poor clinical outcome in human breast
      cancer.
AB  - BACKGROUND: Telomerase is a ribonucleoprotein enzyme that synthesises telomeres
      after cell division and maintains chromosomal length and stability thus leading
      to cellular immortalisation. hTERT (human telomerase reverse transcriptase) gene
      is the rate-limiting determinant of telomerase reactivation. The present study
      aims to quantitatively measure the expression of hTERT mRNA in human breast
      cancer, examine the association between hTERT and the clinicopathological
      characteristics of the cancer specimens including the Nottingham Prognostic Index
      (NPI) and to explore the relationship between hTERT expression and clinical
      outcome. MATERIALS AND METHODS: RNA was extracted from 116 breast carcinomas and
      31 matched adjacent non-cancerous tissue (ANCT). hTERT mRNA expression was
      estimated by reverse transcriptase-PCR (RT-PCR) and Taqman methodology. RESULTS:
      hTERT mRNA was present in all of the cancerous specimens (mean=0.1701,
      median=0.0205) and most ANCT specimens with levels being 2.6 times higher in the
      cancerous tissue than in ANCT (mean=0.156 vs. 0.68, p=0.18). The mean mRNA levels
      increased with NPI scores (0.0816 for NPI 1, 0.1186 for NPI 2 and 0.68 for NPI
      3), however this failed to reach statistical significance (P-values= 0.33 for NPI
      1 vs. 2, 0.27for NPI2 vs. 3 and 0.24 for NPI 1 vs. 3). hTERT levels also
      increased with increasing tumour's grade (mean= 0.0459 for grade 1, 0.111for
      grade 2, and 0.27 for grade 3) but this trend did not reach a statistical
      significance. Low levels of hTERT were associated with mucinous carcinoma
      compared with ductal (p=0.023) and lobular (p=0.021) types. hTERT mRNA levels
      were higher in patients who had recurrent disease or died from breast cancer
      compared with those who remained alive without disease after a median follow up
      of 6 years (p=0.0026). CONCLUSION: High hTERT mRNA levels are associated with a
      poor clinical outcome in human breast cancer and should be included as a
      prognostic marker in future validation studies.

PMID- 17214360
TI  - Quantification in the serum of the catalytic fraction of reverse telomerase: a
      useful prognostic factor in advanced non-small cell lung cancer.
AB  - The purpose of this analysis was to study the association between the quantity of
      free circulating DNA and clinical variables in 99 advanced non-small cell lung
      cancer patients (NSCLC). The quantification in the serum of the gene of the
      catalytic fraction of telomerase (hTERT) by RT-PCR was used as a reference of the
      total amount of free DNA in blood. Patients were treated with cisplatin and
      docetaxel. The median hTERT level for patients in stage IIIB was 70.7 ng/ml vs.
      53.1 ng/ml in patients in stage IV (p= 0.35). There was no association between
      hTERT values and therapy response, 53.9 ng/ml in the complete response (CR) +
      partial response (PR) group vs. 54.1 ng/ml in the stable disease (SD) +
      progressive disease (PD) group (p=0.23). In the multivariate analysis, hTERT was
      an independent predictive variable for time to progression (TTP) Hazard ratio
      (HR) 2.0, CI 95% 1.2-3.4, p=0.009) and overall survival (OS) (HR 2.4 CI 95% 1.3
      4.3, p=0.004). The analysis of TTP and OS with a cut-off of hTERT at 40 ng/ml
      revealed that patients about this level had statistically poorer TTP (4 vs. 7
      months, p= 0.009) and OS (5 vs. 15 months, p<0.0001). In conclusion, in advanced
      NSCLC, high serum hTERT levels may be a poor prognostic indicator for TTP and OS.

PMID- 17214362
TI  - Extensive local and systemic therapy in extraneural metastasized glioblastoma
      multiforme.
AB  - Cases of extracranial metastases of glioblastoma multiforme to sites such as
      bones, spleen, lung, liver and kidneys have been reported but available
      information about treatment of organ and bone metastases is extremely scarce. In
      this report a case of glioblastoma multiforme (GBM) of the temporal lobe with
      subsequent liver and bone metastases is described and the success of different
      chemotherapy regimens is discussed. Liver and bone metastases were effectively
      treated with temozolomide and later with carboplatin and docetaxel. Two years
      after first diagnosis symptomatic local recurrence occurred. Therefore a
      stereotactic fractionated radiotherapy was performed. As a result of relapse of
      liver metastases the patient received chemotherapy with adriamycin,
      cyclophosphamide and etoposide. Visceral metastases were stable, but nevertheless
      the patient died from local progression 3 years after first diagnosis. In
      conclusion, liver metastases of GBM can be effectively treated by chemotherapy.
      This case report suggests suitable substances which can be chosen according to
      clinical circumstances.

PMID- 17214361
TI  - Activity of combination chemotherapy, docetaxel and epirubicin as neoadjuvant
      therapy for women with breast cancer.
AB  - BACKGROUND: This study assesses the efficacy of epirubicin and docetaxel as
      neoadjuvant therapy for women with breast cancer. PATIENTS AND METHODS: This is a
      single institution, single arm, phase II study of epirubicin given at 75 mg/m(2)
      and docetaxel at 75 mg/m(2) every three weeks for four cycles prior to surgical
      excision in women with large breast cancers. Pegfilgrastim was routinely
      administered as primary prophylaxis against febrile neutropenia. RESULTS: Out of
      the 18 patients enrolled on the study, 12 (66.7%) had a clinical response and 13
      (72.2%) had a pathologic response, with a pathologic complete response of 5.6%.
      Pre-menopausal women and patients with estrogen receptor positive tumors had a
      higher response rate. One patient died due to sepsis and febrile neutropenia.
      CONCLUSION: Combination chemotherapy with epirubicin and docetaxel is highly
      active against breast cancer. With close monitoring for toxicity, this
      combination can be safely administered with mild side-effects.

PMID- 17214363
TI  - Prognostic significance of serum antibodies to HPV-16 L1 virus-like particles in
      patients with invasive cervical cancer.
AB  - BACKGROUND: Persistent infection with high-risk human papilloma virus (HPV) is a
      prerequisite for the development of cervical cancer. The prognostic value of HPV
      16 capsid antibodies in patients with invasive cervical cancer and its
      correlation with clinicopathological factors were investigated. PATIENTS AND
      METHODS: Serum samples from 150 patients with invasive cervical cancer and 40
      healthy female control subjects were analyzed by ELISA for HPV-specific
      antibodies to HPV-16 L1 virus-like particles (VLPs). RESULTS: HPV-16 L1
      antibodies were detectable in 65 out of 150 patients (43.3%) and in 12 out of 40
      controls (30.0%). Seropositivity was correlated with prolonged, progression-free
      (p =0.012) and overall survival (p=0.043). Especially in the early FIGO-stages I
      and II antibodies to HPV-16 L1, VLPs predicted a better outcome. CONCLUSION:
      Antibodies to HPV-16 L1 capsid protein may be of prognostic value for patients
      with invasive cervical cancer and lack of HPV-16 L1 antibodies may indicate a
      group of patients with a poor prognosis.

PMID- 17214364
TI  - Maspin nuclear localization is related to reduced density of tumour-associated
      micro-vessels in laryngeal carcinoma.
AB  - BACKGROUND: MASPIN, a tumour suppressing serpin, is a potent inhibitor of
      angiogenesis. CD105 is a proliferation-associated protein acting in endothelial
      cells of angiogenic tissues. For the first time the relation between nuclear
      MASPIN expression and CD105-assessed micro-vessel density (MVD) in laryngeal
      carcinoma was investigated. PATIENTS AND METHODS: The sub-cellular distribution
      of MASPIN and nuclear MASPIN expression were immunohistochemically determined in
      35 cases of laryngeal carcinoma. The percentage of the fields occupied by CDl05
      assessed micro-vessels was also calculated. RESULTS: MVD was significantly lower
      in laryngeal carcinomas with MASPIN nuclear staining than in carcinomas with
      cytoplasmic staining (p=0.02). The mean nuclear MASPIN expression was higher in
      patients without carcinoma recurrence than in those with recurrence (p=0.06). The
      mean MVD was significantly higher in patients with recurrence of carcinoma
      (p=0.024). CONCLUSION: The crucial role of MASPIN nuclear localization in
      reducing the MVD has been demonstrated. Nuclear MASPIN re-expression should be
      investigated as a potential therapeutic option in the treatment of laryngeal
      carcinoma.

PMID- 17214365
TI  - Retrospective analysis of the superior vena cava syndrome in irradiated cancer
      patients.
AB  - BACKGROUND: A carcinoma is the underlying cause of superior vena cava syndrome
      (SVCS) in 95-97% of patients. The aim of our study is to retrospectively analyse
      the outcome of patients after local radiotherapy compared to literature data.
      PATIENTS AND METHODS: In 35 consecutively registered patients, irradiated because
      of SVCS, different primary carcinomas (lung, breast, head-and-neck, Non-Hodgkin's
      lymphoma) were ascertained. Distant metastases had already been diagnosed in 33
      patients. Chemotherapy had previously been given in seven patients. RESULTS: In
      30 patients, radiotherapy obtained a reduction of symptoms within 5-9 days.
      However, in seven patients, radiotherapy had to be stopped early because of local
      progress and tumor induced complications. Local recurrences were observed in six
      patients. The 1-year overall survival rate was 15.6%. Survival rate depended
      significantly on the performance status (p < 0.004). CONCLUSION: Based on
      literature data our results are comparable regarding the incidence, the radio
      oncological procedure and the response to treatment. These data confirm that
      radiotherapy is the standard treatment in most patients suffering from SVCS.
      However, it should be determined if endovascular stenting, which is more
      frequently considered in the last few years in patients with a tumor induced
      SVCS, may be a useful option as a simultaneous or sequentially given treatment to
      optimize the palliative effect.

PMID- 17214366
TI  - Chromosome-12 copy number alterations and MDM2, CDK4 and TP53 expression in soft
      tissue liposarcoma.
AB  - BACKGROUND: Liposarcoma is a heterogeneous group of soft tissue sarcomas in which
      definitive prognostic parameters need to be identified. MATERIALS AND METHODS:
      The series included 33 consecutive soft tissue (well-differentiated, WDLPS, n=19;
      and dedifferentiated, DDLPS, n=14) liposarcoma. Clinicopathological variables
      included age, gender, body location, degree of dedifferentiation and mitotic
      count. The rrolecular analysis included MDM2, CDK4 and TP53 expressions and
      chromosome-12 copy number alterations. RESULTS: Centrally located
      (retroperitoneal, abdominal cavity or groin region) WDLPS had more
      dedifferentiation (p=0.001). Patients with DDLPS and a high mitotic rate died
      (p=0.070) or experienced recurrencies (p=0.029) more frequently. Co-expression of
      MDM2/CDK4 (p=0.001) and TP53 accumulation (p=0.017) related to dedifferentiation
      but not to recurrence or death, both in WDLPS and DDLPS. DDLPS had higher
      centromeric chromosome-12 copy number than WDLPS (p=0.013), but this was
      unrelated to recurrence or death. CONCLUSION: Central location is a risk factor
      in WDLP. Co-expression of MDM2/CDK4/TP53 and chromosome-12 alterations
      characterize DDLPS suggesting a link with dedifferentiation.

PMID- 17214367
TI  - CD46 expression is indicative of shorter revival-free survival for ovarian cancer
      patients.
AB  - BACKGROUND: The membrane cofactor protein CD46 represents a complement inhibitor,
      which protects autologous cells from complement - mediated cytotoxicity. CD46 may
      exhibit the potential to protect tumor cells from the immune responses of the
      host. The present study aimed to evaluate the prognostic significance of CD46
      expression in ovarian cancers. MATERIALS AND METHODS: The analyses were performed
      on 73 ovarian cancer samples. Immunohistochemical reactions were performed on
      paraffin sections of tumors using monoclonal antibodies directed against CD46.
      The immunohistochemical reactions and the clinical observations results were
      subjected to statistical analysis. RESULTS: Expression of CD46 was demonstrated
      in 60% of primary laparotomy cases and in 70% secondary cytoreduction cases.
      Kaplan-Meier analysis showed that a significantly shorter revival-free time was
      linked to cases with CD46 expression at PL (p= 0.01). CONCLUSION: Ovarian cancers
      manifest CD46 expression that is linked to a less favourable prognosis.

PMID- 17214368
TI  - Expression of Syk in invasive breast cancer: correlation to proliferation and
      invasiveness.
AB  - BACKGROUND: Spleen tyrosine kinase (Syk) kinase has recently been considered as a
      tumor suppressor gene in breast cancer. MATERIALS AND METHODS: Syk expression in
      patients with invasive breast cancer was immunohistochemically assessed. RESULTS:
      Decreased expression was found in 26% of the specimens examined. In cases with
      vascular invasion, expression of Syk was lost in the intravascular emboli. A
      significant relationship between increased proliferation levels (as estimated by
      the proliferative index, Ki67) and decreased Syk expression (p <0.05) was found.
      CONCLUSION: Our data suggest that Syk protein expression inversely correlates
      with the proliferation and invasive capacity of breast cancer.

PMID- 17214369
TI  - DNA repair gene polymorphisms and bladder cancer susceptibility in a Turkish
      population.
AB  - BACKGROUND: Occupational exposure and life style preferences, such as smoking are
      the main known environmental susceptibility factors for bladder cancer. A growing
      list of chemicals has been shown to induce oxidative DNA damage. Base excision
      repair (BER) genes (X-ray repair cross complementing 1, XRCC1 and human 8
      oxoguanine DNA glycosylase 1, OGG1) may play a key role in maintaining genome
      integrity and preventing cancer development. MATERIALS AND METHODS: We tested
      whether polymorphisms in XRCC1 and OGG1 are associated with bladder cancer risk
      by using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR
      RFLP) assay. In addition, the possible modifying affect of cigarette smoking was
      evaluated. RESULTS: No studies, to date, have examined the association between
      genetic polymorphisms in DNA repair genes and bladder cancer susceptibility, in
      the Turkish population. We found the OGG1 Cys326Cys genotype to be more frequent
      among bladder cancer patients (odds ratio (OR): 2.41 (95% CI, 1.36-4.25)).
      However, in the case of XRCC1, there was no significant difference in
      susceptibility to bladder cancer development between patients with the Arg399 and
      these with the Gln399 allele (OR. 0.72 (95% CI, 0.41-1.26)). CONCLUSION: Our data
      showed that OGG1 genetic polymorphisms might be useful as prognostic genetic
      markers for bladder cancer in the clinical setting.

PMID- 17214370
TI  - Concomitant radiochemotherapy with temozolomide in non-selected patients with
      newly diagnosed high-grade gliomas.
AB  - BACKGROUND: Malignant gliomas still present a medical challenge, despite decades
      of continuous extensive research with optimization of surgical techniques,
      radiotherapy and systemic treatments. PATIENTS AND METHODS: From 1999 to 2004,
      104 patients with WHO grade III and IVgliomas underwent surgery and received
      concomitant radiotherapy combined with concomitant oral temozolomide. Patients
      with progressive disease received sequential 5-day cycles of temozolomide at 28
      day intervals. RESULTS: The median overall survival was 19.7 and 15.0 months for
      patients with WHO grade III versus IV gliomas, respectively. Patient compliance
      was good and toxicity moderate. The overall survival was as long as 18.0 months
      in a subgroup of subjects with glioblastoma, performance status >60% and complete
      radiochemotherapy. CONCLUSION: Although our patients had more negative
      characteristics (age, performance, biopsy only), the results confirmed those from
      recently published optimistic phase III trial data and indeed surpassed them in
      some cases.

PMID- 17214371
TI  - Stable hematopoietic recovery after peripheral blood stem cell transplantation in
      patients receiving high-dose chemotherapy for advanced germ cell tumors.
AB  - AIM: The objective of this study was to evaluate the utility of CD34-positive
      peripheral blood stem cell transplantation (PBSCT) in the hematopoietic recovery,
      in patients receiving high-dose chemotherapy (HDCT), for advanced germ cell tumor
      (GCT). MATERIALS AND METHODS: This study included 41 patients with advanced GCT,
      who were treated with HTCT combined with PBSCT. PBSCs were harvested after
      conditioning chemotherapy followed by the administration of granulocyte colony
      stimulating factor. A retrospective analysis of a total of 86 PBSCTs was carried
      out focusing on the effects of several factors, including age (<35 years versus >
      or = 35 years), CD34-positive cell dose (<5.0 x10(6)/kg versus > or =5.0
      x10(6)/kg), indication of HDCT (first-line versus salvage) and previous history
      of HDCT before PBSCT (with versus without), on hematopoietic recovery after
      PBSCT. RESULTS: The median number of CD34-positive PBSCs collected during a
      single apheresis and the median cumulative number of CD34-positive PBSCs from
      each patient were 8.3x10(6)/kg and 23.2x10(6)/kg, respectively. The median number
      of PBSCT performed in each patient was two and the median number of CD34-positive
      cells transplanted during a single course was 5.7x10(6)/kg. The median recovery
      times to white blood cells (WBC) greater than 500/microl, 1000/microl and
      2000/microl were 8, 9 and 10 days, respectively, following PBSCT, while that to
      neutrophils greater than 500/microl and that to platelets greater than
      50000/microl were 9 and 13 days, respectively, following PBSCT Only the recovery
      time to platelet count greater than 50000/microl was significantly affected by
      age; however, there were no significant differences in the recovery of WBC,
      neutrophils and platelets in relation to several parameters examined. CONCLUSION:
      These findings suggest that CD34-positive PBSCT may facilitate stable
      hematopoietic recovery after HDCT in patients with advanced GCT, and that HDCT,
      if combined with PBSCT, could be performed with comparative safety in such
      patients, irrespective of their individual characteristics.

PMID- 17214372
TI  - Diagnostic relevance of overexpressed NOK mRNA in breast cancer.
AB  - A novel oncogene with a kinase domain (NOK), a receptor protein tyrosine kinase,
      has been reported to cause proliferation of normal cells, suggesting its possible
      use as a diagnostic marker in human cancer. To determine the significance of NOK
      expression in cancer cells, the effect of NOK inhibition was first examined on
      cell proliferation in vitro. The degree of expression in 52 clinical breast
      cancer samples was then correlated with clinical features. The transduction of
      NOK small inhibitory (si) RNA in T47D breast cancer cells decreased NOK mRNA
      expression, thereby inhibiting growth. When the mean expression in non-cancerous
      tissues from the same breast resection specimens +/-2SD was used as a cut-off
      value, 67.3% of breast cancers were positive for NOK expression - a higher
      positivity rate than that found for c-erbB2 (28.8%). NOK mRNA expression did not
      correlate with c-erbB2 expression, indicating the independence of NOK as a
      diagnostic marker. Furthermore, NOK mRNA was highly expressed even at early
      clinical stages. NOK mRNA might be an ideal target to support the diagnosis of
      breast cancer especially in tiny tumors in which the malignancy cannot be
      confirmed by other means.

PMID- 17214373
TI  - Lack of association between the MDM2-SNP309 polymorphism and breast cancer risk.
AB  - BACKGROUND: A T-to-G polymorphism (SNP309) at the promoter region of MDM2 has
      been recently reported to extend the Sp1 binding site that positively regulates
      the MDM2 transcription level and consequently, its expression level. MDM2 is the
      negative regulator of p53 tumor suppressor protein and elevated levels of MDM2
      hamper the stress response driven by the p53 pathway. Whether MDM2-SNP309 was
      associated with breast cancer as a predisposing factor was investigated. PATIENTS
      AND METHODS: A case-control study of 223 females diagnosed with breast cancer and
      149 female controls sampled from the Turkish population was carried out and the
      T/G MDM2-SNP309 genotype of participants was determined. RESULTS: There was no
      significant association of the G/G or G/T genotypes with breast cancer risk (odds
      ratio (OR) 1.14, 95% confidence interval (CI) 0.59-2.22, and OR 1.20, 95% CI 0.67
      2.12, respectively). Stratification of the data for onset age or for menopausal
      status at the time of diagnosis also revealed no association for either group.

PMID- 17214374
TI  - An increase in basal cell carcinoma among the young: an epidemiological study in
      a middle-south Italian population.
AB  - During the last 20 years, an increasing incidence of basal cell carcinoma (BCC)
      has been demonstrated by several studies. A ten-year retrospective analysis on
      7,266 cases of primary BCC of the Department of Dermatology and Plastic Surgery
      of the University of Rome La Sapienza and the Department of Dermatology of the
      University of Naples "Federico If' is reported. Among a population aged over 35
      years, BCC cases increased from 618 in 1994 up to 749 cases in 2003, while among
      the younger population (<35 years), BCC cases increased from 30 in 1994 to 47
      cases in 2003. Anatomic site distribution of BCC among people aged <35 years was:
      head and neck=51.54%, trunk=41.40%, limbs=5.91%, others= 1.12%. On histological
      examination aggressive-growth BBC was recorded in 48 out of 355 cases (13.52%)
      among people aged <35 years and in 841 out of 6,755 cases (12.45%) among patients
      >35 years. In conclusion, an increasing incidence of basal cell carcinoma among
      young people over the past 20 years was reported. No significant difference in
      tumour aggressiveness between the young and the elderly patients was observed.

PMID- 17214375
TI  - The role of STS and OATP-B mRNA expression in predicting the clinical outcome in
      human breast cancer.
AB  - BACKGROUND: Steroid sulfatase (STS) is the enzyme responsible for hydrolysing
      biologically inactive estrogen sulfates to active estrogens. Therefore it plays a
      significant role in supporting the growth of hormone-dependent tumours of the
      breast, endometrium and prostate. OATP-B is a member of a family of membrane
      transporter proteins that regulates the uptake of steroid sulfates through cell
      membranes. Our objective was to determine, using quantitative PCRA whether the
      mRNA expression levels from these genes were positively correlated with clinical
      outcome in human breast cancer. This is the first study in the literature to
      examine the relationship between STS and OATP-B in human breast cancer and to
      investigate the potential prognostic value of OATP-B. MATERIALS AND METHODS: A
      total of 153 samples (120 tumour tissues and 33 normal breast tissues) were
      analysed. The levels of transcription of STS and OATP-B were determined using
      real-time quantitative PCR and normalized against cytokeratin 19. The levels of
      expression were analysed against tumour's stage, grade, nodal status, local
      relapse, distant metastasis, ERalpha, ERbeta and HER1-4 receptor status and
      survival over a 10 year follow up period. RESULTS: The levels of STS mRNA were
      significantly higher in malignant samples (p=0.031) and in node positive disease
      (p=0.0222). STS mRNA expression increased with increasing tumour grade but this
      did not reach statistical significance. A significant increase was also noted in
      levels correlating with tumour stage when stages TNM1 and TNM2, TNM2 and TNM3,
      and TNM3 and TNM4 (p=0.00001, 0.0017 and 0.02, respectively) were compared.
      Furthermore, STS expression levels positively correlated with progression of
      disease, as levels were significantly higher in samples from patients who
      developed metastasis, local recurrence, or died of breast cancer when compared to
      those who were disease free for >10 years (p=0.0036). No significant correlation
      was found between the levels of STS expression and ERalpha/ERbeta/ status. The
      levels positively correlated with HER1 and HER3 receptors. The levels of mRNA
      expression of OATP-B were higher in malignant tissue compared to normal tissue;
      this, however, did not reach statistical significance (p=0.4045). Levels were
      also higher in node positive disease (p=0.0672). Expression levels increased with
      increasing tumour grade and this became statistically significant when comparing
      grade 1 to 2, and grade 2 to 3 (p=0.0271 and 0.0289, respectively). An increase
      in levels correlating with TNM tumour staging was also observed; this, however,
      did not reach statistical significance. There was no significant correlation
      between OATP-B expression levels and clinical progression of breast cancer. No
      correlation was found between STS and OATP-B expression levels. CONCLUSION: This
      study demonstrates a compelling trend for STS transcription levels to be higher
      in cancer tissues and in patients who developed progressive disease. OATP-B
      expression levels correlated with the grade and stage of the disease, but not
      with the clinical outcome. These results suggest that STS mRNA has a significant
      potential as an important predictor of clinical outcome in patients with breast
      cancer.

PMID- 17214376
TI  - Editorial essay: magic.

PMID- 17214377
TI  - 2-D tilt and 3-D slant illusions in perception and action tasks.
AB  - There is now a well established dissociation between perception and action based
      primarily on neuropsychological evidence [Milner and Goodale, 1995 The Visual
      Brain in Action (Oxford: Oxford University Press)]. Although equivocal, an
      important source of evidence from normal observers is that 'perceptual illusions'
      may affect the systems differently. We investigated the relative effects of 2-D
      tilt and 3-D slant illusions in the two domains, using similar tasks to those
      employed originally by Milner and Goodale. Subjects were required to either post
      a card through, or set a paddle to match the orientation of, a plane that was
      presented in two conditions: surrounded by a striped surface tilted between +90
      degrees and -90 degrees (2-D tilt contrast), or surrounded by a disparity defined
      surface slanted in depth between +60 degrees and -60 degrees (3-D depth
      contrast). For 2-D tilt, action and perception were equally affected by the
      illusion, whereas in the 3-D condition they were not. Here, the illusion appeared
      greater in the posting than in the perceptual task. We conclude that, although no
      qualitative differences exist, there were quantitative differences between
      perception and action tasks in the binocular condition.

PMID- 17214378
TI  - Oppel-Kundt illusion in three-dimensional space.
AB  - A three-dimensional form of the Oppel-Kundt illusion was examined. Subjects
      viewed arrays consisting of two parallel rows of lights. For one group the rows
      consisted of equal numbers of lights (2, 3, or 4), while for a second group the
      row nearest the subject always had the greater number of lights. Subjects viewed
      these arrays from two vantage points, one directly in front of the array and the
      other displaced laterally. For each array subjects adjusted the extent of the far
      array until they felt the two rows were the same length. Both the nature of the
      array and the viewpoint had a significant influence on the perceived length of
      the far row. The size of the near row was overestimated significantly more when
      the array was viewed from the central position and also when the number of lights
      in the near row exceeded that of the far row. These results confirm that a
      lateral viewing position decreases the perspective effect and indicate that the
      Oppel-Kundt illusion can occur with three-dimensional stimuli.

PMID- 17214379
TI  - Central visual persistences: II. Effects of hand and head rotations.
AB  - In an earlier paper, kinesthetic effects on central visual persistences (CPs)
      were reported, including the ability to move these images by hand following eye
      closure. While all CPs could be translated anywhere within the frontal field, the
      present report documents a more selective influence of manual rotations on CPs in
      the same subjects. When common objects or figures drawn on cards were rotated
      (while holding one end of the object or one corner of a card between thumb and
      forefinger), it was found that CPs of larger objects rotated with the hand. By
      contrast, CPs of smaller objects, parts of objects, and textures remained stable
      in space as the hand rotated. It is proposed that CPs of smaller stimuli and
      textures are represented mainly by the ventral stream (temporal cortex) while
      larger CPs, which rotate, are represented mainly by the dorsal stream (parietal
      cortex). A second discovery was that CPs of small objects (but not of line
      segments or textures) could be rotated when the thumb and fingers surrounded the
      edges of the object. It is proposed that neuronal convergence of visual and
      tactile information about shape increases parietal responses to small objects, so
      that their CPs will rotate. Experiments with CPs offer new tools to infer visual
      coding differences between ventral and dorsal streams in man.

PMID- 17214380
TI  - Material-illumination ambiguities and the perception of solid objects.
AB  - The appearance of objects depends on their material, shape, and on the
      illumination conditions. Conversely, object appearance provides us with cues
      about the illumination and the material. This so-called inverse problem is
      basically underdetermined and therefore we expect that material and illumination
      perception are confounded. To gain insight into the relevant mechanisms, we
      rendered a set of artificial spheres for vastly different canonical light fields
      and reflectance functions. We used four physics-based bidirectional reflectance
      distribution functions (BRDFs) representing glossy, pitted, velvety, and matte
      material. The six illumination conditions were collimated illumination from four
      directions, hemispherical diffuse illumination, and fully diffuse (Ganzfeld)
      illumination. In three sub-experiments we presented pairs of stimuli and asked
      human observers to judge whether the material was the same, whether the
      illumination was the same, and for a subset in which either the illumination or
      the material was the same to judge which of the two was constant. We found that
      observers made many errors in all sub-experiments. In experiment 2 the
      illumination direction was chosen at random. Using an interactive interface, we
      asked human observers to match the illumination direction of a sphere of one of
      the four materials with that of a Lambertian sphere. We found systematical
      material-dependent deviations from veridical performance. Theoretical analysis of
      the radiance patterns suggests that judgments were based mainly on the position
      of the shadow edge. In conclusion, we found no evidence for 'material constancy'
      for perception of smooth rendered spheres despite vast quantitative and
      qualitative differences in illumination and in BRDF between the stimuli. Although
      human observers demonstrated some 'illumination constancy', they made systematic
      errors depending on the material reflectance, suggesting that they used mainly
      the location of the shadow edge. Our results suggest that material perception and
      light-field perception are basically confounded.

PMID- 17214381
TI  - Distinct patterns of viewpoint-dependent BOLD activity during common-object
      recognition and mental rotation.
AB  - A fundamental but unanswered question about the human visual system concerns the
      way in which misoriented objects are recognized. One hypothesis maintains that
      representations of incoming stimuli are transformed via parietally based spatial
      normalization mechanisms (eg mental rotation) to match view-specific
      representations in long-term memory. Using fMRI, we tested this hypothesis by
      directly comparing patterns of brain activity evoked during classic mental
      rotation and misoriented object recognition involving everyday objects. BOLD
      activity increased systematically with stimulus rotation within the ventral
      visual stream during object recognition and within the dorsal visual stream
      during mental rotation. More specifically, viewpoint-dependent activity was
      significantly greater in the right superior parietal lobule during mental
      rotation than during object recognition. In contrast, viewpoint-dependent
      activity was significantly greater in the right fusiform gyrus during object
      recognition than during mental rotation. In addition to these differences in
      viewpoint-dependent activity, object recognition and mental rotation produced
      distinct patterns of brain activity, independent of stimulus rotation: object
      recognition resulted in greater overall activity within ventral stream visual
      areas and mental rotation resulted in greater overall activity within dorsal
      stream visual areas. The present results are inconsistent with the hypothesis
      that misoriented object recognition is mediated by structures within the parietal
      lobe that are known to be involved in mental rotation.

PMID- 17214382
TI  - Repetition priming and recognition of dynamic and static chimeras.
AB  - Chimeric faces, produced by combining the top half of a familiar face with the
      bottom half of a different familiar face, are difficult to recognise explicitly.
      However, given that they contain potentially useful configurational and featural
      information for face recognition, they might nevertheless produce some activation
      of representations of their constituent faces. Repetition priming with dynamic
      and static facial chimeras was used to test this possibility. Whereas half-faces
      produced significant repetition priming of their familiar counterparts, both
      types of chimera did not. When analyses were restricted to faces that were
      recognised during the prime phase, repetition priming was both significant, and
      equivalent, for chimeras and half-faces. The results suggest that the
      constituents of a facial chimera must be parsed, and recognised, in order for
      them to cause repetition priming for their familiar counterparts. Facial motion
      does not help with the parsing of a facial chimera.

PMID- 17214383
TI  - Aging and the visual, haptic, and cross-modal perception of natural object shape.
AB  - One hundred observers participated in two experiments designed to investigate
      aging and the perception of natural object shape. In the experiments, younger and
      older observers performed either a same/different shape discrimination task
      (experiment 1) or a cross-modal matching task (experiment 2). Quantitative
      effects of age were found in both experiments. The effect of age in experiment 1
      was limited to cross-modal shape discrimination: there was no effect of age upon
      unimodal (ie within a single perceptual modality) shape discrimination. The
      effect of age in experiment 2 was eliminated when the older observers were either
      given an unlimited amount of time to perform the task or when the number of
      response alternatives was decreased. Overall, the results of the experiments
      reveal that older observers can effectively perceive 3-D shape from both vision
      and haptics.

PMID- 17214384
TI  - Viewpoint and orientation influence picture recognition in the blind.
AB  - In the first three experiments, subjects felt solid geometrical forms and matched
      raised-line pictures to the objects. Performance was best in experiment 1 for top
      views, with shorter response latencies than for side views, front views, or 3-D
      views with foreshortening. In a second experiment with blind participants,
      matching accuracy was not significantly affected by prior visual experience, but
      speed advantages were found for top views, with 3-D views also yielding better
      matching accuracy than side views. There were no performance advantages for
      pictures of objects with a constant cross section in the vertical axis. The early
      blind participants had lower performance for side and frontal views. The objects
      were rotated to oblique orientations in experiment 3. Early-blind subjects
      performed worse than the other subjects given object rotation. Visual experience
      with pictures of objects at many angles could facilitate identification at
      oblique orientations. In experiment 5 with blindfolded sighted subjects, tangible
      pictures were used as targets and as choices. The results yielded superior
      overall performance for 3-D views (mean, M = 74% correct) and much lower matching
      accuracy for top views as targets (M = 58% correct). Performance was highest when
      the target and matching viewpoint were identical, but 3-D views (M = 96% correct)
      were still far better than top views. The accuracy advantage of the top views
      also disappeared when more complex objects were tested in experiment 6.
      Alternative theoretical implications of the results are discussed.

PMID- 17214386
TI  - Eye-witnesses should not do cryptic crosswords prior to identity parades.
AB  - Navon letter tasks have been shown to affect subsequent face recognition
      performance. As such tasks are not likely to by carried out prior to a witness
      attending an identity parade this is unlikely to have much applied relevance.
      Here, however, it is explored how a range of puzzles that witnesses might engage
      in affect face recognition. Cryptic crosswords were found to have a detrimental
      effect on subsequent face recognition, unlike reading, literal crosswords, or
      sudoku. As well as this finding's practical importance, it also provides a
      further insight into the Navon effect on face processing.

PMID- 17214385
TI  - Liquid-specific stimulus properties can be used for haptic perception of the
      amount of liquid in a vessel put in motion.
AB  - We investigated whether people can use haptic liquid-specific information made
      available by shaking the vessel containing the liquid. In experiment 1 we studied
      to what extent people can discriminate between liquid and solid substances and
      determine the amount of substance in the shaken vessel, as well as the effects of
      exploratory procedures on these abilities. Exploratory procedures including
      horizontal shaking of the vessel produced accurate identification of the content
      and more precise judgments for a liquid than for a solid, but vertical lifting
      produced an overestimation of the amount of liquid. In experiment 2 we
      demonstrated that people can discriminate between the amount of liquid and the
      amount of solid in the same vessel. Three theories of what liquid-specific
      stimulus properties are picked up by shaking the vessel are preliminarily
      examined.

PMID- 17214387
TI  - The role of metformin in the treatment of polycystic ovary syndrome (PCOS).
AB  - Hyperinsulinemia is believed to be a key link in the enigmatic generation of the
      symptoms of polycystic ovarian syndrome (PCOS), which include anovulatory
      infertility and the skin stigmata induced by hyperandrogenism. Regression of
      these symptoms may be achieved by reducing the hyperinsulinemia. Metformin, an
      insulin-sensitizing agent, has been proven to be of clinical usefulness both in
      the short-term aiding of infertility treatments and, potentially, in the
      prevention of the long-term sequelae for patients with PCOS.

PMID- 17214388
TI  - The management of the patella in total knee arthroplasty.
AB  - Total knee arthroplasty (TKA) is a well-established procedure, and has proven to
      be durable and effective for the treatment of advanced arthritis of the knee
      joint. Early TKAs did not include patellar replacement and anterior knee pain was
      reported after the procedure had been carried out. The incorporation of patellar
      resurfacing during TKA reduces anterior knee pain, although new complications
      have emerged. These complications include component failure, instability,
      fracture, tendon rupture and soft tissue impingement. Such complications are
      attributed to inferior implant design and improper surgical techniques. Fear of
      sustaining these complications has prohibited surgeons from routine patellar
      resurfacing during TKA. Whether or not to resurface the patella during primary
      TKA is still a controversial topic. There are authors who recommend routine
      resurfacing, some who do not recommend resurfacing and some who suggest selective
      resurfacing. The rationale for and against patellar resurfacing during primary
      TKA has been individually justified and reported in the literature. The selection
      of suitable implants and adherence to proper surgical technique are the
      fundamental principles for the success of TKA. Patella resurfacing during TKA is
      recommended when inflammatory arthritis, an eburnated articular surface and
      patellofemoral maltracking are present; patella preservation is recommended when
      there is a small patella, normal articular surface and normal patellar tracking.
      In long-term follow-up, 60% of nonresurfaced patellas continued to have good
      tracking after TKA. The correct choice of patellar component size, as well as
      implant design, medial placement of the patellar component, rule of no thumb and
      lateral retinaculum release when needed, should be adhered to when performing
      patellar resurfacing during TKA.

PMID- 17214389
TI  - Radioguided sentinel lymph node biopsy in early breast cancer: experience at
      Chang Gung Memorial Hospital.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy can identify regional metastases and
      provides an alternative to axillary dissection that avoids arm morbidity. This
      investigation assessed the accuracy of SLN biopsy for predicting axillary node
      status. METHODS: A total of 174 clinical node-negative breast cancer patients and
      165 SLN biopsies were enrolled. SLN biopsy was performed in a two-day protocol
      with backup axillary dissection: subdermally injected technetium-99 sulfur
      colloid to detect and localize SLN on day one; sentinel node harvesting under
      gamma-counter guidance on day two. Clinicopathological factors were statistically
      analyzed to assess the accuracy of the SLN biopsy. RESULTS: The SLN was
      identified in 94.3% (165 of 175) of cases. SLN biopsy had an accuracy of 98.2%,
      with sensitivity of 93.7%, specificity of 100%, negative predictive value of
      97.5% and positive predictive value of 100%. Three SLN negative cases had non-SLN
      metastasis representing a false-negative rate of 6.3% (3 of 48). Tumor size was
      the only factor statistically correlated with the accuracy of the SLN biopsy. The
      diagnostic accuracy for tumors sized 2 cm or below was 100%. Hematoxylin-eosin
      stain followed by immunohistochemical stain increased the diagnosis of axillary
      metastasis from 25.5% to 29.1%. CONCLUSION: SLN biopsy can accurately forecast
      axillary node status in early breast cancer, particularly in patients with tumor
      sizes of no more than 2 cm.

PMID- 17214390
TI  - Comparative study of laparoscopic and open adrenalectomy.
AB  - BACKGROUND: Laparoscopic adrenalectomy (LA) had become the preferred operation
      for management of adrenal neoplasm. We conducted this cohort study to evaluate
      the outcome of laparoscopic and open adrenalectomy (OA). METHODS: A total of 67
      patients with complete medical records were included in this study. Thirty
      patients underwent OA and the other 37 patients received LA. The intraoperative
      and perioperative data analyses focused on surgery time, blood loss, pain scale
      rating, resumption of oral feeding, hospital stay, complications and
      convalescence. RESULTS: LA was completed in all 37 patients without conversion to
      OA or mortality. The surgery times (203.4 vs. 192.9, p = 0.776) were similar for
      both OA and LA groups. There was less blood loss in the LA group (355.0 vs.
      104.0, p = 0.021). The postoperative pain scale rating was lower in the LA group
      (5.6 vs. 4.5 p = 0.035) as was analgesia demand (57.4 vs. 3.7, p < 0.001). Oral
      feeding resumed earlier in the LA group (91.7 vs. 16.4, p < 0.001) and these
      patients had a shorter postoperative hospital stay (8.4 vs. 3.9, p < 0.001). The
      complication rate in both groups was similar. In the LA group, patients with
      primary aldosteronism had shorter surgery times and less blood loss than patients
      with other tumor types (p < 0.05). CONCLUSIONS: LA results in good surgical
      outcome without increased risks. We suggest that LA should be the preferred
      choice for management of adrenal neoplasms. We also suggest that surgeons
      inexperienced in LA consider beginning with a case of primary hyperaldosteronism.

PMID- 17214391
TI  - Subacromial injections of corticosteroids and xylocaine for painful subacromial
      impingement syndrome.
AB  - BACKGROUND: Subacromial impingement syndrome, with pain and limited motion, is a
      common disease encountered daily in clinics. This study determined the efficacy
      of subacromial injections of corticosteroids and local anesthesia for treatment
      of painful subacromial impingement syndrome. METHODS: A total of 238 shoulders in
      209 patients, with regular follow-up, were enrolled in this study. Mean patient
      age was 51 years (range 31-72 years). Each patient complained of shoulder pain
      with progressive motion limitation present for more than one month, which was not
      relieved by various nonsurgical treatments. The mean duration of symptoms before
      injection was five months (range 1-12 months). Each patient had a positive Neer
      impingement sign, Hawkins impingement sign, painful tendon sign, limited range of
      motion and did not show clinical evidence of a rotator cuff tear. Each patient
      was administered an injection of 1 ml of 2% Xylocaine and 1 ml of Rinderon
      suspension. A second injection was administered one week later for patients
      without obvious improvement. Following injections, patients were instructed to
      perform a home rehabilitation program for four weeks. Follow-up examinations were
      scheduled for one, two and four weeks, and three, six, nine and 12 months after
      injection. Outcome measures included the Constant-Murley score and shoulder range
      of motion. RESULTS: At follow-up four weeks after the first injection, 216
      shoulders (91%) had satisfactory improvement in amount of pain and range of
      motion: mean improvements in the active range of motion of forward elevation,
      abduction, internal rotation and external rotation were 56 degrees, 48 degrees,
      18 degrees and 22 degrees, respectively. However, at the first year follow-up,
      the satisfaction rate was slightly down at 88%, and 19 shoulders (8%; 16
      patients) had recurrent pain and motion limitation after an average of 5.4 months
      (range 3-12 months). Each of these patients received another injection. Surgery
      was recommended for 22 shoulders (9%; 18 patients) that did not have satisfactory
      improvement. Of these patients, eight shoulders (seven patients) had a partial
      tear of the rotator cuff and 10 shoulders (eight patients) had complete rotator
      cuff tears. CONCLUSION: Subacromial injection of corticosteroids and local
      anesthesia is an effective therapy for the treatment of symptomatic subacromial
      pathology, such as impingement pain, tendonitis and bursitis. The injection can
      substantially reduce pain and increase range of motion of the shoulder. If there
      is no improvement following injections, a rotator cuff tear should be suspected.

PMID- 17214392
TI  - Postoperative wound infection rates after posterior instrumented spinal surgery
      in diabetic patients.
AB  - BACKGROUND: Diabetes mellitus is thought to be a risk factor for surgical site
      infection. There have been no reports about the infection rate in diabetic
      patients who have undergone posterior spinal instrumented fusion. We present a
      retrospective analysis of infection rates after posterior spinal instrumented
      fusion in diabetic and non-diabetic patients. METHODS: Of 337 patients who
      underwent posterior spinal instrumented fusion between 1995 and 1997, 39 were
      diabetic. Plasma glucose concentration, body mass index, type of instrument,
      operation time, blood loss, hospital stay and complications were recorded. The
      pathogenic organism and treatments for infection were also described. RESULTS:
      The rate of wound infection in diabetic patients was 10.3% compared with 0.7% in
      non-diabetic patients (p = 0.003). Body mass index and preoperative blood sugar
      were also significantly different between the two groups (p = 0.02, p < 0.001).
      CONCLUSIONS: Patients with a diabetic history or preoperative hyperglycemia had a
      higher infection rate after posterior spinal instrumented fusion when compared
      with non-diabetic patients.

PMID- 17214394
TI  - Comparison of polarimetric retinal nerve fiber analyzer parameters for a single
      high quality image and the mean image from three high quality images.
AB  - BACKGROUND: To find the correlations and differences between the nerve fiber
      layer parameters of a GDx (polarimetric retinal nerve fiber analyzer) in single
      high quality images and those in the mean image from three high quality images.
      METHODS: The results of scanning laser polarimetry were selected from 63 eyes of
      63 patients (31 male and 32 female). Complete ophthalmic examinations included
      slit-lamp biomicroscopy, dilated pupil for vitreous and ocular fundus
      examination, applanation tonometry, and subjective or objective refraction. There
      were no significant ophthalmic disorders other than glaucoma and mild lens
      opacity. Nerve fiber layer thickness of each eye was measured with GDx and at
      least three high quality images (passing the software's quality criteria) were
      obtained. The best of these three high quality images was selected as a single
      high quality image (Group One). The mean image (Group Two) was calculated from
      the same three high quality images. RESULTS: We found that there was a high
      correlation in all nerve fiber layer parameters between Group One and Group Two.
      There was no significant difference in the seven relative values of nerve fiber
      layer parameters (Number, Ellipse Modulation, Symmetry, Superior Ratio, Inferior
      Ratio, Superior/Nasal and Maximal Modulation) between Group One and Group Two.
      Group One had significantly higher values compared with Group Two in the other
      seven absolute values of nerve fiber layer parameters (Average Thickness, Ellipse
      Average, Superior Average, Inferior Average, Superior Integral, Superior Maximal
      and Inferior Maximal). CONCLUSION: It is reasonable to take a mean image from
      three good quality images from a cooperative patient. If only one high quality
      image can be obtained in repeated acquisition of GDx, the seven relative values
      of nerve fiber layer parameters in this high quality image can be used as a base
      line image for detecting retinal nerve fiber layer defects and for determining
      changes of retinal nerve fiber layer thickness in sequential images of GDx.

PMID- 17214393
TI  - Two-year effect of rosiglitazone in chinese poorly controlled type 2 diabetic
      patients.
AB  - BACKGROUND: The goal of this study is to assess the 24-week efficacy of the
      addition of rosiglitazone 4 mg to existing full dose sulfonylurea (SU) and
      metformin (MET) therapy in patients with inadequately controlled type 2 diabetes,
      and to observe the continued follow-up efficacy and safety of this drug for up to
      two years. METHODS: This study consists of 32 patients. Fasting plasma glucose
      (FPG), free fatty acid (FFA), high sensitive C-reactive protein (HS-CRP),
      adiponectin, insulin and C-peptide were measured every four weeks up to week 24.
      After that time, the FPG continued to be checked every month. Glycated hemoglobin
      (HbA1c) and lipid profiles were also checked every 12 weeks for more than two
      years. RESULTS: HbA1c was reduced by 1.4% at week 12 and by 1.1% at week 24.
      However HbA1c was still above 9% throughout the whole study period. FPG was
      reduced significantly when comparing the baseline value to the value after
      treatment. The FPG values after one year and two years follow-up were similar to
      the value at week 24. The serum total cholesterol and low density lipoprotein
      (LDL) cholesterol levels increased significantly. Serum triglycerides were
      reduced significantly. Significant reductions in serum FFA from baseline to week
      24 were observed. A gradually decrease of serum HS-CRP was noted from baseline to
      week 24. Serum adiponectin levels increased maximally at week 12 and then it
      decreased gradually, showing a significant change. Serum insulin and C-peptide
      levels showed significant changes from baseline to week 24. There were no acute
      cardiocerebral peripheral vascular disease events or liver damage within the
      entire study period. CONCLUSIONS: Clinical improvement in glycemic control was
      observed after the addition of rosiglitazone to type 2 diabetic patients
      receiving full dose SU and MET therapy. The maximal effect was observed at week
      12 and the effect continued for at least two years. Further, the combination
      therapy also resulted in an improvement in lipid profiles, decreased HS-CRP and
      increased adiponectin levels in the short term (24 weeks). This combination
      therapy is also safe and beneficial for at least two years because no acute
      episodes of cardiocerebral peripheral vascular disease were seen.

PMID- 17214395
TI  - Flexible iris retractors for management of zonular dialysis during planned
      phacoemulsification.
AB  - BACKGROUND: The aim of this study was to determine the use of flexible iris
      retractors in four patients with zonular dialysis occurring during cataract
      surgery. METHODS: We describe the use of flexible iris retractors to stretch and
      fixate the capsulorhexis over the zonular dehiscence sector for patients with
      traumatic zonular disruption occurring during phacoemulsification, which
      stabilizes the capsular bag and facilitates cataract extraction without
      complications. RESULTS: Each of the four eyes was implanted with posterior
      chamber intraocular lens (PCIOL) successfully. The intraocular lenses (IOLs)
      remained well centered during the 12-month follow-up period and the patients
      enjoyed improved vision without complications. CONCLUSION: Flexible iris
      retractor is a simple, convenient and useful instrument for managing zonular
      dehiscence that occurred during cataract extraction. It facilitates the removal
      of the residual lens material and IOL implantation without major complications.

PMID- 17214396
TI  - Protein-losing enteropathy after the Fontan operation: clinical analysis of nine
      cases.
AB  - BACKGROUND: Protein-losing enteropathy (PLE) is a serious complication of a
      Fontan operation and has a very high mortality rate. The purpose of this study
      was to investigate the incidence, clinical manifestations, diagnostic approaches,
      laboratory findings, therapeutic modalities and outcome of patients with PLE at
      our institution. METHODS: The diagnosis of PLE was based on clinical
      manifestations and laboratory studies. We reviewed medical records of patients
      who received a Fontan operation at our hospital form July 1985 to October 2005.
      RESULTS: A total 101 patients underwent various modifications of the Fontan
      procedure during this period. Nine of the 75 patients (12%) who survived 30 days
      after surgery developed PLE, including 4 boys and 5 girls. The median time
      interval between the Fontan operation and onset of PLE was 3.7 years (range 1.2
      to 9.7 years). Laboratory examination showed low serum albumin levels and
      increased fecal alpha-1-antitrypsin excretion. Lymphangiectasia was found on
      intestinal biopsy. Six patients had cardiac catheterization after development of
      PLE which demonstrated an elevated mean right atrium pressure (22.5 +/- 6.4 mmHg,
      range 16 to 33 mmHg) and mean pulmonary artery pressure (22.3 +/- 6.4 mmHg, range
      16 to 33 mmHg). Treatment included diet modification, albumin infusion,
      diuretics, inotropes, corticosteroids, heparin, and surgery. Four patients
      received medical treatment only. Two of these patients died due to sepsis and
      heart failure and 2 survived with partial relief of PLE. The remaining five
      received surgery for PLE after medical treatment failure. Three of them died
      after the operation and the two survivors were free of PLE, but one died of
      ventricular tachycardia 8 years later. The overall mortality rate was 67% (6/9).
      CONCLUSIONS: The current treatment for PLE is associated with a very high
      mortality rate. Further investigation is needed to determine the exact mechanism
      of the disease and to develop new therapeutic approaches.

PMID- 17214397
TI  - Leukemoid reaction after methotrexate-induced pancytopenia in a patient
      undergoing continuous ambulatory peritoneal dialysis.
AB  - Methotrexate has been used as an important alternative therapy in the treatment
      of various rheumatic diseases. Life threatening marrow suppression in end-stage
      renal disease patients undergoing hemodialysis or continuous ambulatory
      peritoneal dialysis has been reported. A 33-year-old woman with systemic lupus
      erythematosus undergoing chronic peritoneal dialysis developed severe mucositis
      and pancytopenia after low-dose methotrexate treatment for arthritis. The
      leukocyte count recovered after methotrexate was withdrawn but a leukemoid blood
      picture developed during her recovery. No evidence of leukemia was found on bone
      marrow biopsy. The leukocyte count gradually returned to normal with conservative
      therapy.

PMID- 17214398
TI  - Observation of biochemical imaging changes in human pancreatic cancer tissue
      using Fourier-transform infrared microspectroscopy.
AB  - Fourier-transform infrared (FT-IR) microspectroscopic mapping can be used to
      distinguish between different tissue structures, and to increase the image
      contrast between normal and cancerous regions of a given tissue sample. This
      study demonstrates the biochemical changes associated with a consistent link
      between cancerous tissue and various molecular changes in the IR spectra of human
      pancreatic cancer tissue using FT-IR mapping. Tissue samples were obtained
      immediately after resection in a patient who underwent a distal pancreatectomy
      including the pancreatic body and tail. The biochemical imaging changes of
      lipids, proteins, and nucleic acids in human pancreatic cancer tissue were
      analyzed via FT-IR microspectroscopy, using imaging, mapping, and line scan
      techniques. The intensities and frequencies of the absorption bands in the IR
      spectra of human pancreatic cancerous tissue were markedly reduced and shifted,
      particularly in the amide bands of protein and CH2 and CH3 stretching vibrations
      of lipids. The cancerous tissue contained significant protein content, and the
      distributions of DNA and lipid were very low, indicating low amounts of nucleic
      acids and lipids in human pancreatic cancer tissue. The analytical results
      indicate that these FT-IR microspectroscopic biochemical images reflect the
      distribution of cell components, which could be correlated with stained tissue in
      adenocarcinoma in pancreatic tissues. This study with samples of noncancerous and
      cancerous pancreatic tissues has clearly demonstrated that FT-IR
      microspectroscopy using the mapping method can be used for diagnosis.

PMID- 17214399
TI  - Ahmed glaucoma valve implant for childhood glaucoma in Sturge-Weber syndrome with
      choroidal hemangioma.
AB  - We present our experience with implantation of an Ahmed glaucoma valve in a 9
      year-old girl with Sturge-Weber syndrome with choroidal hemangioma. In this case
      of childhood glaucoma, the choice of surgical procedure should be based on the
      efficacy and elimination of intra-and post-operative complications. An Ahmed
      glaucoma valve offered safety and efficacy in controlling glaucoma. This
      technique avoided sudden drops in intraocular pressure and decreases the risk of
      intraoperative and postoperative choroidal effusion and hemorrhage. The surgical
      procedure was not complicated: a one-staged implant was satisfactory and a
      prophylactic sclerostomy was not required.

PMID- 17214400
TI  - Acute myelomonocytic leukemia with abnormal eosinophils: a case report with multi
      modality diagnostic work-up.
AB  - Acute myeloid leukemia (AML) with recurrent genetic abnormalities often carries a
      favorable prognosis. AML with inv(16)(p13q22) occurs predominantly in younger
      patients and usually shows granulocytic and monocytic differentiation with
      abnormal eosinophils. It is referred to as acute myelomonocytic leukemia with
      abnormal eosinophils (AMML Eo). We report a case in a 27-year-old man with
      leukocytosis (10.6 x 10(3)/microL with 34% blasts), thrombocytopenia and
      splenomegaly. Marrow aspiration showed 47% blasts and 33% eosinophils, of which
      19% were morphologically abnormal with both eosinophilic and basophilic
      cytoplasmic granules. Cytochemically, the blasts were positive for
      myeloperoxidase while the granules of abnormal eosinophils were positive for
      naphthol ASD chloroacetate esterase. With flow cytometric immunophenotyping the
      blasts expressed CD13, CD33, CD117, myeloperoxidase and CD34. Marrow trephine
      showed 90% cellularity with 40% blasts expressing CD34, CD117, and
      myeloperoxidase on immunohistochemistry. Chromosomal analysis reveled a karyotype
      of 46, XY, inv(16)(p13q22). This case illustrates a typical AMML Eo confirmed by
      a multi-modality diagnostic approach including morphology, cytochemistry, flow
      cytometry, immunohistochemistry, and conventional cytogenetic study.

PMID- 17214401
TI  - The healthy worker effect in professional football.
AB  - We investigated the "healthy athlete effect" (HAE) in American professional
      football. Ages of death of professional football players who debuted prior to
      1940 were obtained and differences between those ages and age-adjusted life
      expectancies were examined to determine if longevity increased with career
      length, controlling for birth year, body mass index (BMI), position, and type.
      Professional football players (N=1,512) lived an average of 6.1 (+/- 11.9 SD)
      years longer than age-matched controls from the general public. Career length
      significantly and incrementally increased longevity of players from an average of
      5.5 years for players playing one season to 6.7 years for players playing 4 or
      more seasons. Both birth year and BMI had a statistically significant association
      with longevity, but position type did not. These data provide strong support for
      the healthy worker effect (HWE) in professional football.

PMID- 17214402
TI  - Upper body contribution during leg cycling peak power in teenage boys and girls.
AB  - This study investigated gender differences in upper-body contribution to cycle
      muscle power in 23 adolescents. All subjects performed two 5-s and one 20-s
      cycling sprint, using two protocols: with handgrip (WG) and without handgrip
      (WOG). Maximal handgrip strength was assessed for each individual. Absolute peak
      and mean cycling power was corrected for total fat-free mass (FFM) and for lean
      leg volume (LLV). Males showed higher cycling performance than females. Peak
      power and 20-s mean power (flywheel inertia included), but not optimal velocity,
      were higher WG than WOG. Especially for peak power, absolute differences between
      both protocols were higher in males than in females, and were significantly
      related to handgrip strength. The significant contribution of the upper body
      suggested that, for standardisation of cycle muscle power, total FFM is a more
      relevant variable compared with LLV. Furthermore, in adolescents, the higher
      contribution of the upper body musculature in males partly explained gender
      differences in peak power.

PMID- 17214403
TI  - Low-intensity exercise, vascular occlusion, and muscular adaptations.
AB  - The study investigated the effects of low-intensity exercise on muscular fitness
      when combined with vascular occlusion. Nineteen college male and female students
      performed two sets of a 5-min step exercise using a 12-inch bench three times per
      week for 5 weeks. During the step exercise, blood flow to one leg was restricted
      (vascular occlusion) with a blood pressure cuff, while the other leg was not
      occluded. Muscular strength of the occluded leg was significantly increased over
      the nonoccluded leg (p < 0. 05). Muscular endurance and muscle mass were improved
      after 5 weeks of training (p < 0.05); however, the changes between the two legs
      were not significantly different (p > 0.05). Exercise with vascular occlusion has
      the potential to be an alternative form of training to promote muscular strength.

PMID- 17214404
TI  - Proprioceptive and sensorimotor performance in Parkinson's disease.
AB  - We explored the effects of random whole-body vibration on leg proprioception in
      Parkinson's disease (PD). In earlier studies it was found that this treatment
      leads to improved postural control in these patients. Thus, one could speculate
      that these effects result from modified proprioceptive capabilities. Twenty-eight
      PD patients were subdivided in one experimental and one control group.
      Proprioceptive performance was analyzed using a tracking task basing on knee
      extension and flexion movements. Treatment consisted of 5 series of random whole
      body vibration taking 60 seconds each. Control subjects had a rest period
      instead. Prominent over- and undershooting errors were found in both groups
      representing proprioceptive impairments. No significant differences became
      evident, however, either between pre- and post-tests or between experimental and
      control group. One might therefore conclude that spontaneous improvements in
      postural control are not directly connected with proprioceptive changes.
      Nevertheless, one also should keep in mind the general aspects and difficulties
      of analyzing proprioception.

PMID- 17214405
TI  - Yohimbine: the effects on body composition and exercise performance in soccer
      players.
AB  - The main aim of this study was to determine the effects of yohimbine
      supplementation on body composition and exercise performance in professional
      soccer players. The athletes (20 top-level male soccer players) were allocated to
      two randomly assigned trials. Subjects in the yohimbine group orally ingested
      tablets that contains yohimbine at a dose of 20 milligrams per day in two equal
      doses for 21 days. Subjects in the placebo group ingested an equal number of
      identical-looking pills that contained cellulose. There were no statistically
      significant changes in body mass and muscle mass within or between trials (p >
      0.05) after the supplementation protocol. Percentage of body fat significantly
      decreased in the yohimbine group after the supplementation protocol (9.3 +/- 1.1
      vs. 7.1 +/- 2.2%; p < 0.05). Furthermore, fat mass was significantly lower in the
      yohimbine versus placebo trial at postsupplementation assessment (7.1 +/- 2.2 vs.
      9.2 +/- 1.9%; p < 0.05). There were no changes in exercise performance indicators
      (bench and leg press, vertical jump, dribble and power test results, shuttle run)
      within or between. trials (p > 0.05). No subject reported any side effects from
      yohimbine. The results of the current study indicate that supplementation with
      yohimbine combined with resistance training does not significantly alter the body
      mass, muscle mass, or performance indicators in professional soccer players.
      Nonetheless, yohimbine supplementation appears to be suitable as a fat loss
      strategy in elite athletes.

PMID- 17214406
TI  - Evaluation of leg-to-leg BIA in assessing body composition in high-school-aged
      males and females.
AB  - The current investigation was conducted to evaluate the accuracy of the Tanita
      300WA leg-to-leg (LL) bioelectrical impedance analyzer (BIA) for measuring body
      composition in an American high-school-aged population. Body composition was
      determined in 77 students, comparing BIA measurements with the criterion,
      hydrostatic weighing (HW). Among the males, there were no significant differences
      found in percent body fat (%BF) between BIA (14.1 +/- 7.8%) and HW (14.9 +/-
      9.1%); however, skinfolds (SK; 11.8 +/- 7.2%) were significantly different from
      HW. A significant correlation in fat-free mass (FFM) was found between BIA and HW
      (r = 0.96, p < 0.001), and the standard error of estimate (SEE) for FFM was 3.28
      kg for males. In females, a significant difference (p < 0.001) in %BF was found
      for both BIA (26.4 +/- 5.7%) and SK (27.9 +/- 5.1%) when compared with HW (23.6
      +/- 5.9%). The correlation in FFM between BIA and HW was lower (r = 0.78, p <
      0.001) and the SEE for FFM was 2.93 kg for females. The Tanita 300WA LL-BIA
      system is appropriate for assessing body composition in male adolescents, but it
      warrants future research in female adolescents.

PMID- 17214407
TI  - Dental workforce models for the future: national and state.

PMID- 17214408
TI  - Oh, for a magic wand!

PMID- 17214409
TI  - The 2006 gold medal for distinguished service--Dr. Rene Rosas.

PMID- 17214410
TI  - Supervision of Dental auxiliaries. First in a three-part continuing education
      series.

PMID- 17214411
TI  - Expanded functions of dental assistants.

PMID- 17214412
TI  - Pit and fissure sealant certification for dental assistants: are the needs being
      met?

PMID- 17214413
TI  - Cambodian volunteer dental visit.

PMID- 17214414
TI  - Build your practice with "paid-for dentistry".

PMID- 17214415
TI  - Increase your treatment acceptance with one simple step.

PMID- 17214416
TI  - Oral and maxillofacial pathology case of the month. Focal osteoporotic marrow
      defect (Hematopotic bone marrow defect; focal hematopoietic hyperplasia).

PMID- 17214417
TI  - [15 year Longitudinal Aging Study Amsterdam. Theme introduction].

PMID- 17214418
TI  - [Social participation of the 55-64 year olds: is the new generation more socially
      active than its predecessor?].
AB  - Nowadays people speak of the 'new' generation of young old who would be healthier
      and more socially active compared to the earlier generation. Using data from the
      Longitudinal Aging Study Amsterdam it was examined to what degree this is a
      realistic image. The study compared the social participation level of 55-64 year
      olds in 1992 and the same age group in 2002, and aimed to explain the differences
      from cohort differences in four determinants of participation: level of
      education, labour participation, health and partner status. Descriptive analyses
      showed that the younger cohort was more actively involved in voluntary
      organisations and participated more often in cultural and leisure activities
      compared to the older cohort. In addition, the younger cohort was more highly
      educated, yet reported more functional disabilities, and more often hold paid
      jobs compared to the older cohort. No cohort differences were found with respect
      to the proportion of married persons. Logistic regression analyses showed that
      the higher level of social participation of the younger cohort was mainly due to
      the higher level of education, but that this effect was reduced by the larger
      disability of the younger cohort. Job and partner status did not explain the
      cohort differences in social participation. It is concluded that the current
      young old are more socially active and higher educated than their predecessors.
      Their (somewhat) worse health status, however, asks for a more nuanced image of
      the 'new' young old.

PMID- 17214419
TI  - [Unhealthy lifestyles during the life course: association with physical decline
      in late life].
AB  - This study aimed to examine the association between unhealthy lifestyle in young
      age, midlife and/or old age and physical decline in old age, and to examine the
      association between chronic exposure to an unhealthy lifestyle throughout life
      and physical decline in old age. The study sample included 1297 respondents of
      the Longitudinal Aging Study Amsterdam (LASA). Lifestyle in old age (55-85 y) was
      assessed at baseline, while lifestyle in young age (around 25 y) and midlife
      (around 40 y) were assessed retrospectively. Lifestyle factors included physical
      activity, body mass index (BMI), number of alcohol drinks per week and smoking.
      Physical decline was calculated as change in physical performance score between
      baseline and six-year follow-up. Of the lifestyle factors present in old age, a
      BMI of 25-29 vs. BMI <25 kg/m2 (odds ratio (OR) 1.6; 95% confidence interval (CI)
      1.1-2.2) and a BMI of > or =30 vs. BMI <25 kg/m2 (OR 1.8; 95% CI 1.2-2.7) were
      associated with physical decline in old age. Being physically inactive in old age
      was not significantly associated with an increased risk of physical decline,
      however, being physically inactive both in midlife and in old age increased the
      odds of physical decline in old age to 1.6 (95% CI 1.1-2.4) as compared to
      respondents who were physically inactive in midlife and physically active in old
      age. Being overweight in both age periods was associated with an OR of 1.5 (95%
      CI 1.1-2.2). These data suggest that overweight in old age, and chronic exposure
      to physical inactivity or overweight throughout life increases the risk of
      physical decline in old age. Therefore, physical activity and prevention of
      overweight at all ages should be stimulated to prevent physical decline in old
      age.

PMID- 17214420
TI  - [Predictors of dementia, the construction of classification trees].
AB  - In order to identify persons who are at risk for dementia in an early phase, two
      classification trees were developed. Data were used from the Longitudinal Aging
      Study Amsterdam (LASA). The prevalence of dementia in the whole sample was 4.0%.
      In the first tree age seemed to be the strongest predictor, with an increased
      risk for persons older than 75. In this group the positive predictive value
      reached a maximum of 33.3% when the persons had memory complaints and a score on
      the Mini Mental State Examination (MMSE) <24. In a second classification tree,
      age was excluded as a predictor because of high association with the other
      potential predictors. In this tree functional limitations seemed the strongest
      predictor. In the group of persons with at least one functional limitations, the
      positive predictive value reached a maximum of 28.8% when the persons had memory
      complaints and a score <24 on the MMSE. In persons without memory complaints,
      persons with cardiovascular diseases or diabetes were at increased risk of
      dementia. Further research is necessary before these classification trees can be
      implemented in general health care.

PMID- 17214421
TI  - [Predicting loss of mastery in older adults].
AB  - PURPOSE: This study aimed to investigate the risk factors of decreasing mastery
      in old age. An adequate level of mastery is essential in order to preserve the
      ability to maintain self-sufficiency and to cope with changes due to
      deterioration of health. METHOD: Data of the cycles 1998/1999 and 2001/2002 of
      the Longitudinal Aging Study Amsterdam (LASA) were used. Included are respondents
      having data on mastery in the first as well as the second cycle (n=1268). In
      order to identify older persons at risk the method of 'classification tree' was
      used, which enables to define groups at risk of loss of mastery. RESULTS: The
      mastery level decreased beneath risk level within three years in fourteen percent
      of older persons still having sufficient mastery in 1998/1999. The risk of loss
      of mastery doubles in case older persons are suffering from depression and
      increases to fifty-six percent in case of cognitive impairment in addition to
      depression. The risk of loss of mastery increases to 33% in case depressed older
      persons with sufficient cognition are suffering from functional limitations.
      Finally, non-depressive older persons with low self-esteem and low self-efficacy
      are at risk of loss of mastery (38%). The classification tree could identify
      increased risk of loss of mastery in 9.9% of the sample. CONCLUSION: The
      combination of depression and cognitive impairment is the main predictor for
      decreased mastery in older adults. This affects however only a small number of
      respondents. A lower but substantial risk is observed in the combination of
      depression and functional limitations with intact cognition.

PMID- 17214422
TI  - [Religiosity and mood in the last week of life: an explorative approach based on
      after-death proxy-interviews].
AB  - The current contribution focuses on the role of religiousness on aspects of mood
      in the last week of life. After-death interviews with proxy respondents of
      deceased participants of the Longitudinal Aging Study Amsterdam provided
      information on depressive mood and anxiety in the last week of life, as well as
      on a sense of peace with the approaching end of life. Furthermore, the proxy
      respondents were asked about serious physical symptoms in the last week of life,
      cognitive decline, salience of religion, and whether the deceased respondent had
      talked about religion. Other characteristics were derived from the last
      interviews with the respondents when still alive: depressive symptoms, religious
      affiliation, church-attendance, orthodoxy, salience of religion, and cosmic
      transcendence. None of the characteristics of religiousness were significantly
      associated with depressive mood or anxiety as estimated by the proxy-respondent.
      A sense of peace, however, was predicted by higher church-attendance, Protestant
      affiliation (as compared to no affiliation), and the proxy's estimate of the
      salience of religion. It is concluded that religiousness does not affect
      depressive mood or anxiety in the last week of life in the current sample.
      Possibly, religiousness supports a sense of peace, which may be a more
      existential facet of mood, and which is discussed as relevant in the last phase
      of life and in palliative care.

PMID- 17214423
TI  - [The gaze of the others: how the Western medical missionaries viewed the
      traditional Korean medicine].
AB  - It is generally known that the Western medical missionaries played an important
      role in introducing Western medicine into Korea. However, little is known about
      their role in introducing traditional medicine of Korea to the Western world. The
      present paper aims at showing various efforts of the Western medical missionaries
      to understand the Korean traditional medicine and to introduce it to the Western
      world. Allen payed attention to the clinical effect and commercial value of the
      Ginseng; Busteed gave anthropological descriptions of the traditional medical
      practice; Landis translated a part of the most cherished medical textbook of
      Korean traditional medicine Dong-Eui-Bo-Gam (see text) into English; Mills, along
      with his colleagues in Severance Union Medical College, tried more scientific
      approaches toward the traditional medicine. All these various efforts proves that
      the attitudes of the Western medical missionaries cannot be summarized as one
      simplistic view, that is, the orientalism, a term which is quite en vogue today.
      Of course, we cannot deny that there may be such elements, but to simplify the
      whole history as such does not only reflect the fact, but also miss a lot of
      things to be reflected in history.

PMID- 17214424
TI  - [The influence of the devotion movement on the health care in North Korea].
AB  - Since the early 1960s, North Korea has conducted 'devotion movement' under the
      directorship of Kim Il Sung across the nation. As a matter of fact, the movement
      was not a novel invention at all. When North Korean Temporary People's Polity was
      established in 1946, North Korea emphasized the importance of the devoted care of
      health personnel. It meant to reform the people's thought and mind along with
      complementing the lack of human and material resources. Thought reform was not a
      peculiar phenomenon observed in North Korea only. It was particularly stressed
      out among communist countries, including the Soviet Union. However any other
      communist country stresses the importance of thought reform. Devotion movement
      should be viewed as part of this process. As shown in many cases, the extent and
      degree of devotion movement and care are beyond our imagination, which does not
      intend to mean that North Korean health personnel's attitude towards patients is
      superior to the counterparts in South Korea. Indeed human being's behavior cannot
      be understood without taking account of society in general. The question can be
      raised as to whether or not North Korean health personnel's devoted care is
      really voluntary. To put aside the testimony that the most powerless group in a
      society can fall prey to victims, if social environment, whether directly or
      indirectly, is action on the people's thought and mind even in a subtle way and
      thus influence one's decision power, it is hard to highly evaluate the devoted
      care in North Korea. Moreover it seems like that the internal conflict exists
      surrounding devotion. In conclusion, I think that North Korean devotion movement
      has enforced health personnel to reform their thought and mind to adapt to North
      Korean regime and has played an important role to accomplish the purpose of North
      Korean Labor Party to realize essential constituents of its health system, in
      such a situation in which essential medical supplies are severely lacking. But it
      seems like that it plays reverse action to develope sound North Korean health
      system.

PMID- 17214425
TI  - Experimental sciences in surgery: Harvey Cushing's work at the turn of the
      twentieth century.

PMID- 17214426
TI  - [The academic trend of Oriental medicine during the Japanese colonial period as
      observed through the publication of medical books].
AB  - This thesis examines the academical trend of Oriental Medicine in the Japanese
      colonial period observed through medical books published during the Japanese
      colonial period. This is a period in which Western Medicine was introduced, and
      due to the lean-to-one-side policy by the Japanese, Western Medicine became the
      mainstream medical science while Oriental Medicine was pushed to the outskirts.
      Even after all this, the academic activity was flourishing during this period
      compared to any other periods. This article is divided into various chapters each
      with its own theme in order to understand the academic trend of Oriental Medicine
      during the Japanese colonial period. Focusing on the publication of medical
      books, this article is divided and observed according to various themes such as
      the study of Dong-Eui-Bo-Gam (see text), the study of Bang-Yak-Hap-Pyeun (see
      text), the study of Sang-Han-Ron (see text), the study of Sa-sang (see text)
      constitutional medicine, the study of Eui-Hak-Ip-Mun (see text), the study about
      Bu-Yang-Ron (see text), On-Bo-Ron (see text), and pediatrics, compromise between
      Western and Oriental Medicine, the study of experience medicine, the study of
      acupuncture and moxibustion, and etc.

PMID- 17214427
TI  - [The life and works of Han Shin Gwang: a midwife and nurse of Korean modern
      times].
AB  - Han Shin Gwang, born in an early Christian family in Korea in 1902, could get
      western education different from the ordinary Korean girls in that period. She
      participated in the 1919 Samil Independence Movement in her teens, and got
      nursing and midwifery education in a missionary hospital. She got a midwife
      license and worked as a member in an early mother-and-child health center. She
      organized 'Korean Nurses' Association (see text)' in 1924 and focused on public
      health movement as the chairwoman. She actively participated in women's movement
      organizations, and Gwangjoo Student's Movement. She was known to be a
      representative of leading working women, and wrote articles on woman's right, the
      needs and works of nurses and midwives. From late Japanese colonial period, she
      opened her own clinic and devoted herself to midwifery. After the Korean
      Liberation in 1945, she began political movement and went in for a senate
      election. During the Korean War, she founded a shelter for mothers and children
      in help. After the War, she reopened a midwifery clinic and devoted to the works
      of Korean Midwives' Association. Han Shin Gwang's life and works belong to the
      first generation of Korean working women in modern times. She actively
      participated in women's movement, nurses' and midwives professional movement,
      Korea liberation movement, and mother-and-child health movement for 60 years. Her
      life is truly exemplary as one of the first generation of working women in modern
      Korea, distinguished of devotion and calling.

PMID- 17214428
TI  - Avoiding violence by technologies? Rectal feeding in German psychiatry, c. 1860
      85.
AB  - During the nineteenth century, the use of the stomach tube became the preferred
      method to treat the insane refusing to eat. But it was not unusual for this
      practice to result in violence and serious injuries. Especially around 1860, when
      the discussion of non-restraint in German psychiatry reached its climax, other
      methods of dealing with sitophobia became the focus of interest. In particular,
      two psychiatrists who ran a private asylum in Endenich near Bonn, Franz Richarz
      and Bernhard Oebeke, recommended rectal feeding as a means of avoiding violence
      and injury. This paper deals with this method and also outlines the different
      'technologies' used to treat 'abstinent' insane patients.

PMID- 17214429
TI  - Animal magnetism in Spanish medicine (1786-1860).
AB  - This paper studies the reception and development of animal magnetism in Spanish
      medicine. It analyses in turn: the initial rejection of animal magnetism
      influenced by the reports of the French Royal Commissions of 1784; the first
      attempts to implant Mesmerism around 1816; its reluctant acceptance with the
      introduction of phrenology from 1842 onwards; and, finally, its critical
      revision, provoked by issues of legal responsibility, from 1856 to 1860.
      Hypnotism, as a term, began to appear in Spanish medical publications around
      1860.

PMID- 17214430
TI  - Infectious insanities, surgical solutions: Bayard Taylor Holmes, dementia praecox
      and laboratory science in early 20th-century America. Part 2.
AB  - Part I of this article on Bayard Taylor Holmes (1852-1924), a Chicago physician
      and surgeon, detailed his laboratory research on dementia praecox and his
      presumed discovery in 1915 of evidence in support of a focal infection theory of
      its aetiology. In May 1916 he began to experiment with a rational therapy based
      on this theory: abdominal surgery and daily irrigations of the colon. He operated
      first on his own son, who had been afflicted with dementia praecox since 1905,
      but he died four days later. Part II deals with Holmes' continued surgical
      treatment of dementia praecox patients and the outcomes of the operations. It
      also describes how Holmes set up the short-lived Psychiatric Research Laboratory
      of the Psychopathic Hospital at Cook County Hospital in 1917, and discusses the
      dismissal of a key research colleague, H. M. Jones, whose experimental results
      directly contradicted those of Holmes.

PMID- 17214431
TI  - V. A. Kral, the Montreal Hebrew Old People's Home, and benign senescent
      forgetfulness.
AB  - The term Benign Senescent Forgetfulness, introduced in 1958 by V. A. Kral,
      constitutes the origin of the concept of Mild Cognitive Impairment (MCI), a
      widely studied but controversial entity. The ambiguities surrounding MCI warrant
      a re-assessment of its historical origin. Any attempt at an in-depth
      investigation of Kral's works on that subject should begin with a description of
      the patient population and professional arena in the Montreal Hebrew Old People's
      and Sheltering Home, where Kral was a consultant. Based on archival and published
      sources, I describe the Home's facilities, population, staff and
      programmes/services, followed by an overview of the dynamic factors inducing a re
      examination of its mode of operation in the mid-1950s when Kral joined the Home's
      professional staff as a consultant.

PMID- 17214432
TI  - 'Study of several involuntary functions of the apparatus of movement, gripping,
      and voice' by Jean-Marc Gaspard Itard (1825).
AB  - Itard's 1825 paper, written while he was Chief Physician at the National
      Institute for Deaf-Mutes in Paris, demonstrates his empiricist approach to
      medicine. That is, Itard founded his medical practice on sense and experience
      rather than on surgery and medication. If all knowledge came through the senses,
      Itard reasoned, those lacking knowledge or social abilities could be improved by
      appropriate sensory stimulation. This concern with senses and society, along with
      his different approaches to men and women, his references to contemporary cures
      and his comparisons between humans and animals, document early nineteenth-century
      medical and psychological attitudes and treatments. Itard's paper also contains
      what was later recognized as the first clinical observation of Gilles de la
      Tourette Syndrome (TS).

PMID- 17214433
TI  - "In this miserable spot called quarantine": the healthy and unhealthy in
      nineteenth century Australian and Pacific quarantine stations.
AB  - By examining sources created by people who were detained or employed at the
      quarantine stations of Australia and the Western Pacific, this article
      illuminates aspects of the history of disease control that cannot be observed in
      other source material. Most research examining the history of maritime quarantine
      has tended to rely on the records of official and government agencies. As a
      result, discussion has largely been confined to government policy and larger
      issues of the political, economic, and social consequences of maritime disease
      control. This article contributes to the historiography by examining personal
      sources that show how quarantine policy and practice were experienced from the
      perspective of its participants. They reveal the experiences of otherwise
      obscured healthy detainees and illuminate agency among quarantined individuals
      that cannot be observed without these sources.

PMID- 17214434
TI  - The rise and fall of the medical gaze: the political economy of immigrant medical
      inspection in modern America.
AB  - In this paper I examine the mass medical inspections of immigrants to the United
      States from the 1890s through the 1920s. I show how, framed as it was not only by
      nativism and eugenics but also by national industrial imperatives and priorities,
      scientific medicine served dual purposes. On the one hand, the medical exam was a
      tool for managing cultural and biological threats to the nation. There were
      regional variations in medical inspections that reflected the politics of race.
      On the other hand, the medical exam played an important role in the process of
      building an unskilled, highly mobile labor force. The industrial demands of the
      nation provided a rationale for drawing and absorbing millions of European
      immigrants into the labor force. It was thus a distinct product of the political
      economy of immigration. It was this second function that characterized the exam
      for the majority of immigrants entering the nation.

PMID- 17214435
TI  - Inoculating against barbarism? State medicine and immigrant policy in turn-of-the
      century Argentina.
AB  - The border in turn-of-the-century Argentina was a place of heightened anxiety.
      State officials ignored the nation's vast land borders and focused on the port,
      located in the capital city of Buenos Aires, which attracted nearly six million
      European immigrants in the decades after 1870. Federal authorities were seeking
      to attract new immigrants and yet they were terrified that opening their gates
      would allow entry among the potential citizenry a new category of "toxins"
      dangerous to the national body. The authorities hired physicians as gatekeepers
      to identify desirable and undesirable traits that went beyond the definition of
      communicable disease. Science and medicine appeared to provide a means of
      legitimating a variety of attempts by the state to control the makeup of the
      population; in reality, the state's power to inspect immigrants for disease,
      racial toxins, social upheaval, and political instability was minimized by
      realistic decisions to open borders and by a weak and limited ability to control
      the influx of people. Alongside calls for immigrant selection there coexisted a
      strong trend in political discourse that sought to build a unified, homogenous
      national culture by accepting and assimilating the foreign masses. Both
      approaches, however, had similar goals--the material progress of the nation, the
      advancement of Argentina's "civilization," and the erasure of traces of
      "foreignness" among the new population.

PMID- 17214436
TI  - Colonial malariology, medical borders, and sharing scientific knowledge in
      mandatory Palestine.
AB  - This article focuses on the specific ways in which Zionist scientists studying
      malaria in Mandatory Palestine (1920-1947) presented their work to international
      scientific circles, moving between the transnational aspects and the local
      aspects of their work on malaria while suffusing that work with nationalist
      meanings. This slippery yet seemingly unproblematic movement between the general
      and the specific, between the colonial world and Palestine, was a necessary
      mechanism of scientific exchange. In the Zionist case the work on malaria for
      these scientists was both a marker of their belief in progress and also a sign of
      their devotion to a specific political and social project. The knowledge imparted
      by Zionist malariologists and the international reception it received lent
      scientific legitimacy to the Zionist project while it advanced the goals of
      settling the land and defining the communal borders within Palestine between the
      Arab population and the Jewish one. In this way, the Zionist anti-malaria project
      in Palestine holds a unique place in malaria research of the time.

PMID- 17214437
TI  - "Belsenitis": liberating Belsen, its hospitals, UNRRA, and selection for re
      emigration, 1945-1948.
AB  - The liberation of the concentration camp at Bergen-Belsen has remained
      controversial with opinion divided over whether the British military and
      subsequently the British zonal administration responded adequately to the plight
      of survivors. This paper reconsiders the evidence on health conditions at Bergen
      Belsen. At first the British underestimated the incidence of typhus and the delay
      in taking effective measures caused the death rate to remain high. In the longer
      term, measures for psychotic, old, and infirm DPs were inadequate as criteria
      that favored the fit and able-bodied were applied when selecting migrants.

PMID- 17214438
TI  - Measuring adaptability: psychological examinations of Jewish detainees in Cyprus
      internment camps.
AB  - Two medical delegations, one from Palestine and one from the United States, were
      sent to detainment camps in Cyprus in the summer of 1947. The British Mandatory
      government had set up these camps in the summer of 1946 to stem the flow of
      Jewish immigrants into Palestine after World War II. The purpose of the medical
      delegations was to screen the camps' inhabitants and to propose a mental-health
      program for their life in Palestine. We examine the activities of these two
      delegations within the context of their scientific interest in the psycho
      pathology of displaced persons after World War II and as part of a broader
      project of mental hygiene. According to the delegations, the detainees would be a
      potential source of strength for building a new society if they adapted to life
      in Palestine. However, they would become a burden if they failed to be absorbed.
      At the same time, the medical delegations also saw the detainee camps as a
      potential "living laboratory" for scientific exploration. The case of the two
      medical delegations in Cyprus is also a story about constructing and
      transgressing medical borders. Apart from the obvious fact that this case study
      deals with movement of people, refugees as well as health-care workers, it is
      also about the transmission of knowledge and professions across the ocean.

PMID- 17214439
TI  - Structure-aided design of inhibitors of Mycobacterium tuberculosis thymidylate
      kinase.
AB  - Antiviral chemotherapy often relies on nucleoside analogues, which, once
      phophorylated by intracellular kinases, target viral polymerases and preclude DNA
      synthesis. In contrast, common antibacterial drugs are rarely related to such
      compounds. In this work TMPKmt, which is essential to DNA replication, was
      selected as a promising target for inhibitor design. Our work demonstrates that
      judicious and stepwise modifications of the substrate structure of TMPKmt, guided
      by the feedback of the enzyme assays as well as by the enzyme's X-ray structure,
      proved a valuable approach to produce a submicromolar inhibitor of this target
      enzyme. This inhibitor was also capable to inhibit bacterial growth. Perhaps more
      importantly, some of the reported thymidine analogues also represent valuable
      tools to better understand the structure and the mechanism of this intriguing
      enzyme.

PMID- 17214440
TI  - [The causes and mechanism of selective motor neuron death in amyotrophic lateral
      sclerosis].
AB  - Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by the
      selective death of motor neurons in the motor cortex, brain stem and spinal cord.
      In most cases, the cause of ALS is unknown although in a number of familial ALS
      cases mutations in the superoxide dismutase 1 (SOD1) gene were discovered. The
      mechanism underlying the selective motor neuron death is not yet clarified.
      However, it is clear that excitotoxicity could play a role in the selectivity of
      the motor neuron death. Excitotoxicity is the phenomenon in which the normal
      glutamate-mediated communication between neurons is disturbed and ultimately
      leads to neuronal death. In the first part of this study, we have investigated
      the intrinsic characteristics of motor neurons that could be responsible for the
      fact that these cells are extremely sensitive to excitotoxicity. Despite the fact
      that only the motor neurons die during ALS, it is clear that also other cell
      types play an important role during this process. In the second part of this
      study, we have concentrated on the potential role of the microglia. These cells
      are the macrophages of the brain and they become activated during inflammation.
      Using minocycline, we have inhibited the activation of the microglia and we have
      investigated its effect on the start of the disease and on the survival of a
      mouse model for ALS. Furthermore, we have investigated the cellular mechanism
      underlying the effect of minocycline. The goal of this research is to get insight
      into the mechanisms responsible for the selective motor neuron death during ALS
      and we hope that this information can help in the development of a therapy for
      this dramatic and incurable disease.

PMID- 17214441
TI  - PDZ domain-phosphoinositide interactions in cell-signaling.
AB  - Proteins containing PDZ domains function as scaffolds for the formation and
      spatial confinement of large signaling complexes. They play an important role in
      the establishment and maintenance of cell polarity and neuronal connectivity.
      Therefore, they are intensively studied in the context of neurobiology and
      cancer. It is well established that PDZ domains are protein-interaction modules
      recognizing short peptide sequences generally situated at the C-terminal end of
      transmembrane receptors. Yet, it is not clear how those interactions are
      regulated. Our recent studies revealed that PDZ domains can also interact with
      phosphoinositides (PIPs), signaling lipids with key-roles in receptor signal
      transduction, membrane trafficking, cytoskeleton remodeling, subcellular
      compartmentalization and nuclear processes. In particular, we established that
      the PDZ domains of syntenin-1 and syntenin-2 bind to phosphatidylinositol 4, 5
      bisphosphate (PIP2) with high-affinity. Syntenin-1/PIP2 interaction is important
      for receptor cargo recycling and syntenin-2 plays a role in the organization of
      nuclear PIP2. Those study cases indicate that cellular phosphoinositides might
      function as essential regulators of PDZ proteins. Here, we summarize and discuss
      our present knowledge about the occurrence, the biochemistry and the
      functionality of PDZ domain-lipid interactions.

PMID- 17214442
TI  - Chemistry, mechanics and the making of anatomical knowledge: Boerhaave vs. Ruysch
      on the nature of the glands.
AB  - A controversy between the well-known medical teacher Herman Boerhaave and the
      anatomist Frederik Ruysch on the nature of the glands shows how chemical
      knowledge had a decisive influence on the way in which Boerhaave perceived the
      anatomy and working of the glands. While Ruysch maintained that the glands are no
      more than the extremities of arteries and act as mechanical instruments
      separating the fluids into smaller particles, Boerhaave examined the glands as
      membranous follicles in which chemical processes prepare the fluids for their
      different uses in the body. Boerhaave, in other words, turned to the chemical
      properties of particles rather than the vessels that contain them. Boerhaave's
      viewpoint was new and resulted from his belief in chemistry as the discipline par
      excellence for the explanation of the most basic processes in the body. More than
      anything else, the controversy shows how chemistry was not contained within fixed
      disciplinary boundaries, but had a decisive influence on Boerhaave's construction
      of anatomical knowledge.

PMID- 17214443
TI  - Medicines, monopolies and mortars: the chemical laboratory and pharmaceutical
      trade at the Society of Apothecaries in the eighteenth century.
AB  - In 1672, a laboratory was founded by the Society of Apothecaries at its premises
      in Blackfriars, London, to manufacture chemical medicines. By exploring the
      society's motivations for constructing a laboratory and its development during
      the eighteenth century, this paper examines the roles that chemistry played
      within the activities of the institution. While the chemistry's primary utility
      was in drug manufacturing for the society's pharmaceutical trade, through its
      laboratory, the society used chemistry to develop its corporate and educational
      aims, thus helping to secure its institutional authority in London's medical
      marketplace.

PMID- 17214444
TI  - A lesson learned: an editorial view on dealing with clinical mistakes and a
      clinical view on editorial mistakes.

PMID- 17214445
TI  - Psychophysiological and subjective sexual arousal to visual sexual stimuli in new
      women.

PMID- 17214446
TI  - "All the rest is normal". A pilot study on the communication between physician
      and patient in prenatal diagnosis.
AB  - The aim of the study was to verify in the context of prenatal diagnosis if the
      communicative style in consultations is modified in relation to the seriousness
      of the diagnosis. Videoed consultations after executing amniocentesis and ultra
      sound scanning of II level were included in the study with the consent of
      participants. Only visits with Italian speaking couples without psychiatric
      problems were analyzed for the study. Selected visits were grouped into "low" (L,
      minor anomalies) and "high" (H, serious anomalies) visits. A modified version of
      the RIAS tailored for the specific context was used in the analysis. 27 visits,
      respectively 13 H and 14 L, were studied. Analysis of the communicative structure
      of the consultations did not show significant differences between the two groups.
      The communication during the consultation seems to be mostly influenced by a
      highly disease-centered model that is not dependent on the content of the
      consultation itself. Only emotional exchanges showed a marginally significant
      decrease in the H visits (t = 1.995, p = 0.057), suggesting the probable
      difficulty of the disease-centered model to manage emotional items during a
      highly dramatic consultation. Due to the exploratory nature of the study, further
      research is needed to test the preliminary results.

PMID- 17214447
TI  - Autonomic nervous system activity in the late luteal phase of eumenorrheic women
      with premenstrual symptomatology.
AB  - The majority of women of reproductive age experience a regular recurrence of
      various symptoms in the premenstrual phase. The etiopathogenesis of premenstrual
      symptomatology, however, remains inconclusive. The present study was proposed to
      evaluate whether the activity of the autonomic nervous system (ANS), which
      largely contributes to the relative stability of a human's internal environment,
      is altered during the menstrual cycle of women with premenstrual symptomatology.
      Thirty eumenorrheic young women participated in this study. All subjects were
      investigated during the follicular and late luteal phases. The ANS activity was
      assessed by means of heart rate variability power spectral analysis during supine
      rest. No intramenstrual cycle differences in the ANS activity were found in women
      experiencing no or small increases in premenstrual symptoms. In contrast, the
      sympathetic nervous system (SNS) activity significantly increased and the
      parasympathetic nervous system (PNS) activity apparently decreased in the late
      luteal phase in subjects whose premenstrual symptomatology was not unbearable,
      but substantially increased (> 20%) compared to the symptom-free follicular
      phase. The women with greater degrees of premenstrual distress possessed higher
      SNS activity and lower PNS activity in the late luteal phase than the women with
      less symptomatology. The ANS activity in the follicular phase did not differ
      among the subjects regardless of their premenstrual symptoms. Although causes and
      consequences continue to elude, the present study provides additional intriguing
      evidence that the altered functioning of ANS in the late luteal phase could be
      associated with diverse psychosomatic or behavioral symptoms appearing
      premenstrually.

PMID- 17214448
TI  - Prenatal maternal stress is associated with delivery analgesia and unplanned
      cesareans.
AB  - We tested the hypothesis that women with greater prenatal maternal stress (PNMS)
      would be more likely to receive intravenous opiates and epidural for delivery,
      and thereby increase the likelihood of unplanned cesarean delivery. PNMS was
      assessed during early, mid, and late pregnancy using psychometrically sound
      instruments in structured interviews with women receiving prenatal care at a
      public university clinic. Medical records were abstracted for analgesia during
      delivery, fetal heart tracing (FHT) abnormalities, and method of delivery. Only
      subjects attempting vaginal delivery (N = 298) were included. Using structural
      equation modeling, a PNMS variable was constructed from five indicators:
      pregnancy-specific distress, number of prenatal stressful life events, distress
      from life events, state anxiety, and perceived stress. After controlling for
      medical predictors of analgesia receipt and surgical delivery, women with higher
      PNMS were more likely to receive analgesia, and those who received analgesia were
      more likely to deliver surgically. Analgesia was also associated with FHT
      abnormalities, which in turn was associated with surgical delivery (all p's <
      0.05). Women who received both an epidural and meperidine were most likely to
      have a cesarean delivery; 29% of this group delivered surgically. Results
      indicate that PNMS contributes to higher likelihood of unplanned cesarean
      delivery through its association with delivery analgesia.

PMID- 17214449
TI  - Obstetric pain relief and its association with remembrance of labor pain at two
      months and one year after birth.
AB  - The association between obstetric pain relief and long-term memory of pain is
      poorly researched in spite of the fact that a woman's memory of childbirth may
      affect her emotional wellbeing and future reproduction. The aim of this study was
      to investigate the association between epidural analgesia and other forms of pain
      relief, and memory of pain at two months and one year after birth. A national
      sample of 2482 Swedish speaking women with vaginal delivery or emergency cesarean
      section preceded by labor were followed from early pregnancy to one year after
      birth. Data were collected by three postal questionnaires: in early pregnancy,
      and two months and one year after the birth. Recollection of intense pain at two
      months and one year was associated with high rates of pain relief, and this was
      most obvious regarding epidural analgesia in first-time mothers. When comparing
      women with the same pain score at two months postpartum who had and who did not
      have an epidural, the first group seemed to have greater difficulty forgetting
      pain 10 months later. Possible explanations of these findings are discussed.

PMID- 17214451
TI  - Factors influencing the quality of intimate relationships six months after
      delivery--first-time parents' own views and coping strategies.
AB  - The aim of this study was to describe and analyze first-time parents' experiences
      of factors that affect the quality of their intimate relationship and the way
      they cope with their situation six months after delivery. The method used was
      inductive qualitative content analysis of two open questions in a larger
      questionnaire. The data is based on 535 respondents' statements. The factors
      affecting the quality of the intimate relationship were available or missing and
      could be classified into four categories. 1. 'Coping by adjustment to parental
      role', e.g., mutual support as new parents, 2. 'The couple's 'intimacy', i.e.,
      togetherness and love, 3. 'Coping by communication', i.e., verbal and non-verbal
      mutual confirmation, and 4. 'Coping with external conditions', e.g., by seeking
      social support. The results are described in a model, which could constitute a
      basis for the promotion of health in family health care, with the aim, if
      possible, of preventing unnecessary separations/divorces after couples become
      parents.

PMID- 17214450
TI  - Anxiety symptoms during pregnancy and postpartum.
AB  - This cross-sectional study compared the distribution of anxiety symptoms among
      pregnant, non-pregnant, and postpartum women of lower socioeconomic status.
      Participants were 807 women who were pregnant (24-36 weeks), postpartum (2-8
      weeks), or not pregnant. Anxiety and depressive symptoms were assessed by the
      state-trait anxiety index and the Beck depression inventory, respectively.
      English and Spanish versions of the instrument were available. Group differences
      in anxiety were evaluated using analysis of variance. Multivariate regression was
      performed to evaluate differences in anxiety while controlling for marital
      status, education, race/ethnicity, employment, cohabitation, income, parity,
      history of depression/anxiety, and depressive symptoms. Anxiety scores were lower
      among postpartum women relative to pregnant and non-pregnant women (both P <
      0.001), who did not differ (P = 0.99). After controlling for depressive symptoms
      and patient characteristics, anxiety remained lowest among postpartum women.
      Additionally, history of depression/anxiety and depressive symptoms were
      significant predictors of anxiety in the multivariate analysis. Comparatively low
      anxiety and depressive symptoms were observed among women who were 2-8 weeks
      postpartum. Anxiety symptoms that occur postpartum may not appear until later in
      the postpartum period.

PMID- 17214452
TI  - The impact of miscarriage on women's pregnancy-specific anxiety and feelings of
      prenatal maternal-fetal attachment during the course of a subsequent pregnancy:
      an exploratory follow-up study.
AB  - This study assesses the implications a miscarriage history has on women's
      pregnancy-specific anxiety and feelings of prenatal maternal-fetal attachment
      during the 1st and 3rd trimesters of a subsequent pregnancy. Thirty-five pregnant
      women (N = 10 with a history of miscarriage) volunteered participation completing
      the Pregnancy Outcome Questionnaire (POQ), the Maternal Antenatal Attachment
      Scale (MAAS and a demographic/reproductive history questionnaire during the first
      trimester of pregnancy. Of these, 24 participants completed the measures again
      during the third trimester of pregnancy. Women with a miscarriage history
      reported significantly higher pregnancy-specific anxiety at trimester 1 than
      women with no miscarriage history; even when the effects of parity were
      controlled. All expectant mothers, irrespective of miscarriage history, scored
      similarly at trimester 1 on the MAAS scales. By the 3rd trimester, pregnancy
      specific anxiety had significantly decreased for women with a miscarriage history
      whose mean scores on the POQ were now similar to women with no history of
      miscarriage. Maternal-fetal attachment had significantly risen by the 3rd
      trimester for all women. These findings suggest that having a miscarriage history
      may not have a long-lasting adverse effect on woman's psychological adaptation
      during the course of a subsequent pregnancy.

PMID- 17214453
TI  - Effects of proximity on the relaxation dynamics of flindersine and 6(5H)
      phenanthridinone.
AB  - The role played by the carbonyl group in the antenna system of a naturally
      occurring photochromic chromene, flindersine (FL), has been experimentally
      investigated and compared with that of a carbonyl group present in a structurally
      related unreactive heterocyclic compound, 6(5H)-phenanthridinone (PH). Through
      stationary and time-resolved absorption and emission techniques, the excited
      state relaxation dynamics after UV irradiation were determined for FL and PH. The
      presence of a carbonyl group in both compounds entails the existence of two close
      lying, strongly coupled electronic excited states, having n,pi* and pi,pi*
      character, respectively. Their coupling can be modulated by a careful choice of
      the solvent proticity and temperature. Moreover, in the case of strong coupling
      between the n,pi* and pi,pi* states, we have proved that the relaxation dynamics
      can involve transitions in which the upper of the coupled states acts as an
      intermediate for radiationless decay, bypassing the lowest emissive state,
      whereby the fluorescence quantum yield becomes a function of the excitation
      wavelength.

PMID- 17214454
TI  - Sputtering of C(60) fullerenes physisorbed on Ar, Xe, H(2)O, O(2), and C(8)F(18)
      matrix films studied with time-of-flight secondary ion mass spectrometry.
AB  - The ionization and fragmentation of C(60) fullerenes were investigated using
      matrix films covered with C(60) molecules and bombarded with 1.5-KeV He(+) ions.
      C(+), C(60)(+), and C(60)(++) ions were sputtered from the C(60) molecules that
      were physisorbed on Ar and Xe matrix films, whereas the sputtering of C(60) on
      the O(2) and C(8)F(18) matrix films induced an additional emission of ion
      adducts, such as (OC(60))(+) and (FC(60))(+), as well as the fragment ions, C(60
      2n)(+) (n = 1-10). Very few ions were sputtered from the C(60) molecules that
      were adsorbed on the H(2)O matrix film and the Ni(111) substrate. The ions are
      thought to be created at the surface when C (C(60)) collides with the Ar, Xe, O,
      and F species via the electron-promotion mechanism, and the formation of quasi
      molecules is manifested from the emission of the ion adducts. The fragmentation
      occurs during the interaction with the reactive species at the surface, and the
      delayed ionization/fragmentation of the internally excited C(60) molecules in the
      gas phase has negligible contribution in the present experiment. The matrix
      effect arises from the suppressed neutralization of the C(60)(+) ion because of
      the localization of a valence hole. The C(60)(+) ion undergoes neutralization on
      the H(2)O film because the hydrogen bond has some covalent character.

PMID- 17214455
TI  - The behavior of exciplex decay processes and interplay of radiationless
      transition and preliminary reorganization mechanisms of electron transfer in
      loose and tight pairs of reactants.
AB  - Exciplex emission spectra and rate constants of their decay via internal
      conversion and intersystem crossing are studied and discussed in terms of
      conventional radiationless transition approach. Exciplexes of 9-cyanophenanthrene
      with 1,2,3-trimethoxybenzene and 1,3,5-trimethoxybenzene were studied in heptane,
      toluene, butyl acetate, dichloromethane, butyronitrile, and acetonitrile. A
      better description of spectra and rate constants is obtained using 0-0 transition
      energy and Gauss broadening of vibrational bands rather than the free energy of
      electron transfer and reorganization energy. The coincidence of parameters
      describing exciplex emission spectra and dependence of exciplex decay rate
      constants on energy gap gives the evidence of radiationless quantum transition
      mechanism rather than thermally activated medium reorganization mechanism of
      charge recombination in exciplexes and excited charge transfer complexes (contact
      radical ion pairs) as well as in solvent separated radical ion pairs.
      Radiationless quantum transition mechanism is shown to provide an appropriate
      description also for the main features of exergonic excited-state charge
      separation reactions if fast mutual transformations of loose and tight pairs of
      reactants are considered. In particular, very fast electron transfer (ET) in
      tight pairs of reactants with strong electronic coupling of locally excited and
      charge transfer states can prevent the observation of an inverted region in
      bimolecular excited-state charge separation even for highly exergonic reactions.

PMID- 17214456
TI  - Parity alternation of ground-state P(n)(-) and P(n)(+) (n = 3-15) phosphorus
      clusters.
AB  - The ground-state structures of neutral, cationic, and anionic phosphorus clusters
      P(n), P(n)(+), and P(n)(-) (n = 3-15) have been calculated using the B3LYP/6
      311+G* density functional method. The P(n)(+) and P(n)(-) (n = 3-15) clusters
      with odd n were found to be more stable than those with even n, and we provide a
      satisfactory explanation for such trends based on concepts of energy difference,
      ionization potential, electron affinity, and incremental binding energy. The
      result of odd/even alternations is in good accord with the relative intensities
      of cationic and anionic phosphorus clusters observed in mass spectrometric
      studies.

PMID- 17214457
TI  - Intermolecular electron transfer from excited benzophenone ketyl radical.
AB  - The electron transfer from the benzophenone ketyl radical in the excited state
      (BPH(.-)(D(1))) to several quenchers (Qs) was investigated using
      nanosecond/picosecond two-color two-laser flash photolysis and
      nanosecond/nanosecond two-color two-laser flash photolysis. The electron transfer
      from BPH(.-)(D(1)) to Qs was confirmed by the transient absorption and
      fluorescence quenching measurements. The intermolecular electron-transfer rate
      constants were determined using the Stern-Volmer analysis. The driving force
      dependence of the electron-transfer rate was revealed.

PMID- 17214458
TI  - Deprotonation dynamics and stokes shift of pyranine (HPTS).
AB  - The short and intermediate time scale dynamics of the photoacid pyranine (1
      hydroxy-3,6,8-pyrenetrisulfonic acid, commonly referred to as HPTS) are studied
      with visible pump-probe spectroscopy in various solvents to elucidate the nature
      of its proton-transfer kinetics in water. The observed time dependences of HPTS
      are compared with those of the methoxy derivative, MPTS. A global fitting
      procedure is employed to model both the spectral shift (Stokes shift) caused by
      solvent reorganization and deprotonation of pyranine in water. Three distinct
      time-dependent features can be clearly identified. They are the Stokes shift (1
      ps in H(2)O and 1.5 ps in D(2)O), followed by the deprotonation processes, which
      gives rise to a biexponential decay of the protonated species with time constants
      (in H(2)O) of 3 and 88 ps. By the use of a model previously discussed in the
      literature, the biexponential process can be interpreted as an initial
      deprotonation step followed by the longer time scale process which separates the
      resulting ion pair. The results presented here are consistent with some of the
      previous reports but unambiguously identify and quantitatively measure the Stokes
      shift as a separate and distinct phenomenon from the deprotonation process, in
      contrast to other reports that have suggested that all short time (a few
      picoseconds) dynamics are merely a Stokes shift.

PMID- 17214459
TI  - An ab initio study of the excited States, isomerization energy profiles and
      conical intersections of a chiral cyclohexylidene derivative.
AB  - The excited valence and Rydberg states of the chiral (4-methylcyclohexylidene)
      fluoromethane (4MCF) have been investigated using multiconfigurational CASSCF and
      CASPT2, and coupled-cluster methods (RI-CC2). A 3s Rydberg state is predicted
      below the valence (1)pipi* state. To gain insight into the photophysics of the
      cis-trans isomerization of this olefin, potential energy profiles for the valence
      (10pipi* state along the twisting and pyramidalization reaction coordinates have
      been computed using variational methods (CASSCF and multireference configuration
      interaction with singles and doubles (MR-CISD)). Starting from geometries with
      energies close to degeneracy in the valence and ground-state curves, three minima
      on the crossing seam that can be correlated with the conical intersections known
      for fluoroethylene, have been found. On the basis of these features, the
      photochemistry of 4MCF is discussed.

PMID- 17214460
TI  - Excited states and two-photon absorption of some novel thiophenyl Pt(II)-ethynyl
      derivatives.
AB  - The photophysical characterization of two new compounds related to bis((4
      (phenylethynyl)phenyl)ethynyl)bis(tributylphosphine)platinum(II), here
      abbreviated Pt1, is reported. For the first new compound ATP1, the inner phenyl
      rings (closer to the Pt atom) in Pt1 are replaced by thiophene rings bridging at
      the 2,5-positions. In compound ATP2, the outer phenyl groups are replaced by
      thiophene rings bonded at the 2-position. Specifically, we report on the
      fluorescence quantum yield, two-photon absorption, triplet decay times and two
      photon absorption induced emission spectra of the molecules in THF solutions. The
      results were compared with those of Pt1 and Pt1 capped with an acetonide
      protected 2,2-bis(methylol)propionic acid (bis-MPA) ester group (Pt1-G1). The
      photophysical properties of the organic dye 7-(diethylamino)coumarin (Coumarin
      110) were determined and used as a reference material. The two-photon absorption
      cross section around 720-740 nm of ATP1 and ATP2 was found to be of the same
      order of magnitude as for Pt1-G1, i.e., between 5 and 10 GM, but slightly larger
      for ATP1 than for ATP2 (1 GM = 1 Goppert-Mayer = 10(-50) (cm(4) s)/photon). The
      fluorescence decay time of all compounds was found to be very short
      (subnanosecond) with quantum yields 0.0045, 0.0007, 0.0011 and 0.0020 for ATP1,
      ATP2, Pt1-G1 and Pt1, respectively, measured at excitation wavelength 373 nm.
      Just as Pt1 and Pt1-G1, both thiophenyl derivatives showed large intersystem
      crossing capabilities and phosphorescence, characteristic for a triplet state
      that can enhance the nonlinear absorption and optical power limiting by triplet
      state absorption. The phosphorescence emission of the thiophenyl derivatives was
      red-shifted in comparison with Pt1 and Pt1-G1, and the phosphorescence decay
      times were on the order of 200-500 ns, as for the Pt1 compound.

PMID- 17214461
TI  - Accurate calculation of the phenyl radical's magnetic inequivalency, relative
      orientations of its spin hamiltonian tensors, and its electronic spectrum.
AB  - The phenyl radical's electronic structure, magnetic inequivalency, spin
      Hamiltonian tensor components, and the relative orientation of their principal
      axes are computed by Neese's coupled-perturbed Kohn-Sham hybrid density
      functional (CPKS-HDF) technique in a moderate amount of time without resorting to
      expensive post-Hartree-Fock techniques. The g tensor component values are in
      excellent agreement with those determined experimentally and differ by less than
      370 ppm. The computed hydrogen nuclear hyperfine tensors, A(1H), are also found
      to be in very good agreement with their experimental counterparts. The
      correlation of the radical's electronic structure with its g and A numerical
      values corroborates that it has a 2A(1) ground state. In accordance with our
      previous studies on the equivalency of planar radicals that possess C(2v)
      symmetry, the in-plane g and A(1H) principal axes should not be parallel to one
      another. Consequently, the spatially equivalent ortho (1H(2), 1H(6)) and meta
      (1H(3), 1H(5)) proton pairs should be magnetically inequivalent. This was
      confirmed in both the present computations and the simulation of the EPR solid
      state spectrum. To the best of our knowledge, this is the first aromatic in-plane
      sigma-type radical whose magnetic inequivalency is studied both computationally
      and experimentally. To properly interpret the radical's electronic excitation
      spectra, the spectroscopy-oriented dedicated difference configuration interaction
      (SORCI) procedure was employed. Aside from a slight overestimation, the method
      seems to be capable of reproducing the C(6)H(5)* electronic vertical excitation
      energies in the range of 0-50,000 cm(-1). These vertical excitations, in
      conjunction with the corresponding orbit and spin orbit matrix elements, were
      also used to compute the g tensor components, employing the sum-over-states
      technique. Due to the limited number of computed roots and excited states, the
      results were marginally inferior to those obtained using the CPKS-HDF method.

PMID- 17214463
TI  - Theoretical evidence for C-F bond activation by a fluoro-calix[4]pyrrole-tert
      amine macrocycle.
AB  - Density functional theory as well as highly correlated ab initio molecular
      orbital theory was used to explore the possibility of activating C-F bonds in
      fluoroalkanes by organic macrocycles. The results indicate that the reaction
      between fluoro-calix [4]pyrrole-tert-amine and CH3F via a Menshutkin displacement
      mechanism is highly favorable and competitive from a thermochemical point of view
      with the very efficient C-Cl activation by a simple macrocyclic amine recently
      reported in the literature (Stanger, L. J.; Noll, B. C.; Gonzalez, C.; Marquez,
      M.; Smith, B. D. J. Am. Chem. Soc. 2005, 127, 4184).

PMID- 17214462
TI  - Quantum treatment of hydrogen nuclei in primary kinetic isotope effects in a
      thermal [1,5]-sigmatropic hydrogen (or deuterium) shift from (Z)-1,3-pentadiene.
AB  - The geometric and kinetic isotope effects (GIE and KIE) for thermal [1,5]
      sigmatropic H and D shifts of (Z)-1,3-pentadiene were studied by including the
      direct quantum effect of the migrating H or D nucleus in the multi-component
      molecular orbital-Hartree-Fock (MC_MO-HF) method. Based on the results, the C(1)
      D bond lengths are 0.007 Angstrom shorter than the C1-H bond lengths in both the
      reactant (A) and the transition states (TS), whereas other bond lengths resemble
      those between H and D. The ratio of the rate constant (k(H)/k(D)) of the reaction
      for the thermal [1,5]-H and D shifts determined using the MC_MO-HF method (8.28)
      is closer to the experimental value (12.2) than that determined using either the
      conventional restricted Hartree-Fock (4.10) or restricted Moller-Plesset second
      order perturbation (3.79) methods.

PMID- 17214464
TI  - Theoretical studies on the excited states, DNA photocleavage, and spectral
      properties of complex [Ru(phen)(2)(6-OH-dppz)](2+).
AB  - The structures and related properties of the complex [Ru(phen)2(6-OH-dppz)]2+
      (phen = 1,10-phenanthroline; dppz = dipyrido [3,2-a:2',3'-c]phenazine) in the
      ground state (S0), the first singlet excited state (S1), and the first triplet
      excited state (T1) have been studied using density functional theory (DFT), time
      dependent (TD) DFT, Hartree-Fock (HF), and configuration interaction singles
      (CIS) methods. Three electronic absorption-spectral bands (1MLCT, 1LL, and 1LL)
      lying in the range of 250-550 nm in vacuo and in aqueous solution were
      theoretically calculated, simulated, and assigned with TDDFT method. In
      particular, the theoretical results show the following: (1) The positive charges
      of central Ru atom in the excited states (S1 and T1) are greatly increased
      relative to those in the ground state (S0), and thus the Ru atom in the excited
      states can be regarded as Ru(III). (2) The positive charges on the main ligand (6
      OH-dppz) in the excited states are considerably reduced, and thus the interaction
      between the main ligand (intercalative ligand) and DNA base pairs is considerably
      weakened. (3) The geometric structures in excited states are also distorted,
      resulting in obvious increase in the coordination bond length. It is advantageous
      to the complex forming a high oxidizing center (i.e., Ru(III) ion). On the basis
      of these results, a theoretical explanation on photoinduced oxidation reduction
      mechanism of DNA photocleavage by [Ru(phen)2(6-OH-dppz)](2+) has been presented.

PMID- 17214465
TI  - Enantioselectivity reversal by achiral additives in the Soai reaction: a kinetic
      understanding.
AB  - Numerical kinetic simulations have been employed to understand the origin of
      enantioselectivity reversal of chiral beta-amino alcohol catalysts occurring in
      the presence of their achiral analogs in the autocatalytic addition of
      diisopropylzinc to pyrimidine carbaldehydes (Soai reaction). In a preceding work
      (Rivera Islas, J.; Lavabre, D.; Grevy, J. M.; HernAndez Lamoneda, R.; Rojas
      Cabrera, H.; Micheau, J. C.; Buhse, T. Proc. Natl. Acad. Sci. U.S.A. 2005, 102,
      13743-13748), we provided a possible explanation for the phenomenon of
      spontaneous mirror-symmetry breaking observed in this reaction. The effect of
      enantioselectivity reversal, giving rise to steep and abrupt transitions between
      opposed optically active states, has been identified by our current approach as
      another manifestation of such mirror-symmetry breaking capability. In the present
      case, we considered the involvement of the chiral catalyst and its achiral analog
      in the reaction network. Our modeling indicates that the enantioselectivity
      reversal can be either caused (i) by an interaction between the chiral and
      achiral additives or (ii) by an interaction of the customary products of the Soai
      reaction with the additives. The second option, which stands for the reversible
      inhibition of the chirally selective autocatalysts by the additives, could also
      explain a number of further additive effects in the Soai reaction reflecting the
      extraordinary sensitivity of this system toward the initial addition of almost
      any, even catalytically inactive, chiral substance.

PMID- 17214466
TI  - Electronic structures and spectroscopic properties of mono- and binuclear d(8)
      complexes: a theoretical exploration on promising phosphorescent materials.
AB  - The structures of trans-[M(2)(CN)(4)(PH(2)CH(2)PH(2))(2)] (M = Pt (1), Pd (2),
      and Ni (3)), trans-[Pt(2)X(4)(PH(2)CH(2)PH(2))(2)] (X = Cl (4) and Br (5)), and
      trans-[M(CN)(2)(PH(3))(2)] (M = Pt (6), Pd (7), and Ni (8)) in the ground state
      were optimized using the MP2 method. Frequency calculations reveal that the weak
      metal-metal interaction is essentially attractive for 1, 2, 4, and 5 but not for
      3. The TD-DFT calculations associated with the polarized continuum model (PCM)
      were performed to predict absorption spectra in CH(2)Cl(2) solution. Experimental
      spectra are well reproduced by our results. With respect to analogous mononuclear
      d(8) complexes (6-8), a large red shift of the absorption wavelength was
      calculated for the binuclear d(8) complexes (1-3). Relative to 1 with unsaturated
      CN- donors, introduction of saturated halogen donors into 4 and 5 changes their
      electronic structures, especially the HOMO and LUMO. The TD-DFT and subsequent
      unrestricted MP2 calculations predict that 1 produces the lowest-energy d --> p
      emission while 2-5 favor the d --> d emissions, agreeing with experimental
      observations.

PMID- 17214467
TI  - Electronic interactions and their influence on the conformational stability of
      trans-2-halocyclopentanol.
AB  - Conformational preferences and electronic interactions of trans-2
      fluorocyclopentanol (1), trans-2-chlorocyclopentanol (2), and trans-2
      bromocyclopentanol (3) were analyzed using experimental and theoretical (3)J(HH)
      coupling constants, theoretical calculations, and natural bond orbital (NBO)
      analysis. The conformational equilibria of compounds 1-3 can be represented by
      their diaxial and diequatorial conformers as supported by theoretical
      calculations. From (3)J(HH) coupling constant values, it can be found that the
      diequatorial conformer is present in the equilibrium as 55% for compound 1 and as
      60% for compounds 2 and 3. This behavior is in agreement with orbital interaction
      analyses obtained from NBO.

PMID- 17214468
TI  - Spectroscopic characterization of novel polycyclic aromatic polymers.
AB  - A series of novel polyphenylenevinylene (PPV) derivative polymers were studied by
      absorption and photoluminescence spectroscopies. The effect of the sequential
      introduction of polycyclic aromatic ring substituents into the delocalized
      backbone was examined with relation to hypsochromatic and bathochromatic
      shifting. While the replacement of the phenyl units by naphthyl units results in
      a substantial hypsochromic shift of both the absorption and emission spectra,
      their subsequent substitution by anthryl units results in a bathochromic shift.
      The system is modeled according to, and is found to be consistent with, a
      previous study of donor-acceptor polyenes of varying length. The electronic
      structure of the backbone is found to be a balance between that of the high
      electron affinity polycyclic ring system and the contribution to conjugation
      across the linking vinyl unit. The model is adapted based on electron affinities
      of the constituent units, and a clear structure-property relationship for the
      absorption and emission properties of the system is elucidated. The Stokes shift
      is examined and is seen to be well-correlated with the vinyl contribution to the
      electron affinity total (EAtotal). The trends observed in the optical properties
      of the polymeric system are supported by Raman spectroscopy, whereby the spectral
      signature of the connecting vinyl bond is seen to soften in a fashion which is
      correlated with the modeled electron affinity parameters.

PMID- 17214469
TI  - Kinetic and mechanistic studies of the I(2)/O(3) photochemistry.
AB  - The atmospherically relevant chemistry generated by photolysis of I2/O3 mixtures
      has been studied at 298 K in the pressure range from 10 to 400 hPa by using a
      laboratory flash photolysis setup combining atomic resonance and molecular
      absorption spectroscopy. The temporal behaviors of I, I(2), IO, and OIO have been
      retrieved. Conventional kinetic methods and numerical modeling have been applied
      to investigate the IO self-reaction and the secondary chemistry. A pressure
      independent value of k(IO + IO) = (7.6 +/- 1.1) x 10(-11) cm(3) molecule-1 s(-1)
      has been determined. The pressure dependence of the branching ratios for the I +
      OIO and IOIO product channels in the IO + IO reaction have been determined and
      have values of 0.45 +/- 0.10 and 0.44 +/- 0.13 at 400 hPa, respectively. The
      branching ratios for the 2I + O(2) and I(2) + O(2) product channels are pressure
      independent with values of 0.09 +/- 0.06 and 0.05 +/- 0.03, respectively. The
      sensitivity analysis indicates that the isomer IOIO is more thermally stable than
      predicted by theoretical calculations. A reaction scheme comprising OIO
      polymerization steps has been shown to be consistent with the temporal behaviors
      recorded in this study. For simplicity, the rate coefficient has been assumed to
      be the same for each reaction (OIO)(n) + IO --> (OIO)(n+1), n = 1, 2, 3, 4. The
      lower limit obtained for this rate coefficient is (1.2 +/- 0.3) x 10(-10) cm(3)
      molecule(-1) s(-1) at 400 hPa. Evidence for the participation of IO in the
      polymerization mechanism also has been found. The rate coefficient for IO
      attachment to OIO and to small polymers has been determined to be larger than (5
      +/- 2) x 10(-11) cm(3) molecule(-1) s(-1) at 400 hPa. These results provide
      supporting evidence for atmospheric particle formation induced by polymerization
      of iodine oxides.

PMID- 17214470
TI  - Structures of the hexafluorocyclopropane, octafluorocyclobutane, and
      decafluorocyclopentane radical anions probed by experimental and computational
      studies of anisotropic electron spin resonance (ESR) spectra.
AB  - Anisotropic electron spin resonance (ESR) spectra are reported for the radical
      anions of hexafluorocyclopropane (c-C(3)F(6)(-)), octafluorocyclobutane (c
      C(4)F(8)(-)), and decafluorocyclopentane (c-C(5)F(10)(-)) generated via gamma
      irradiation in plastically crystalline tetramethylsilane (TMS) and rigid 2
      methyltetrahydrofuran (MTHF) matrices. By combining the analysis of these
      experimental ESR spectra involving anisotropic hyperfine (hf) couplings with a
      series of quantum chemical computations, the geometrical and electronic structure
      of these unusual perfluorocycloalkane radical anions have been characterized more
      fully than in previous studies that considered only the isotropic couplings.
      Unrestricted Hartree-Fock (UHF) computations with the 6-311+G(d,p) basis set
      predict planar ring structures for all three radical anions, the ground
      electronic states being (2)A(2)(") for c-C(3)F(6)(-) (D(3h) symmetry), (2)A(2u)
      for c-C(4)F(8)(-) (D(4h)), and (2)A(2)(") for c-C(5)F(10)(-) (D(5h)), in which
      the respective six, eight, and ten 19F-atoms are equivalent by symmetry. A
      successful test of the theoretical computation is indicated by the fact that the
      isotropic 19F hf couplings computed by the B3LYP method with the 6-311+G(2df,p)
      basis set for the optimized geometries are in almost perfect agreement with the
      experimental values: viz., 19.8 mT (exp) vs 19.78 mT (calc) for c-C(3)F(6)(-);
      14.85 mT (exp) vs 14.84 mT (calc) for c-C(4)F(8)(-); 11.6 mT (exp) vs 11.65 mT
      (calc) for c-C(5)F(10)(-). Consequently, the same computation method has been
      applied to calculate the almost axially symmetric anisotropic 19F hf couplings
      for the magnetically equivalent 19F atoms: (-4.90 mT, -4.84 mT, 9.75 mT) for c
      C(3)F(6), (-3.54 mT, -3.48 mT, 7.02 mT) for c-C(4)F(8)(-), and (-2.62 mT, -2.56
      mT, 5.18 mT) for c-C(5)F(10)(-). ESR spectral simulations performed using the
      computed principal values of the hf couplings and the spatial orientations of the
      19F nuclei as input parameters reveal an excellent fit to the experimental
      anisotropic ESR spectra of c-C(3)F(6)(-), c-C(4)F(8)(-), and c-C(5)F(10)(-),
      thereby providing a convincing proof of the highly symmetric D(nh) structures
      that are predicted for these negative ions. Furthermore, using the computed 19F
      principal values and their orientations, the effective 19F anisotropic hf
      couplings along the molecular symmetry axes were evaluated for c-C(3)F(6)(-) and
      c-C(4)F(8)(-) and successfully correlated with the positions of the
      characteristic outermost features in both the experimental and calculated
      anisotropic spectra. In addition, the electronic excitation energies and
      oscillator strengths for the c-C(3)F(6)(-) , c-C(4)F(8)(-), and c-C(5)F(10)(-)
      radical anions were computed for the first time using time-dependent density
      functional theory (TD-DFT) methods.

PMID- 17214471
TI  - Molecular dynamics simulation of the reaction of hydration of formaldehyde using
      a potential based on solute-solvent interaction energy components.
AB  - Molecular dynamics simulations of aqueous solutions at infinite dilution of the
      reaction of water with formaldehyde, H(2)O + H(2)CO --> H(2)C(OH)(2), were
      performed using Lennard-Jones 12-6-1 potentials to describe the solute-solvent
      interactions, and TIP3P to describe the water-water interactions. The Morokuma
      decomposition scheme of ab initio interaction energies at the SCF level and the
      dispersion component at MP2 level were used to reproduce the molecular parameters
      of the solute-water interaction potential. The results show that the functions
      that use the EX-PL-DIS-ES interaction model to describe the solvation of the
      reactant and product systems lead to good values of the reaction (DeltaG) and
      activation (DeltaG(#)) free energy as compared with those from using AMBER
      derived parameters, and with the available theoretical and experimental data.

PMID- 17214472
TI  - Short strong hydrogen bonds in 2-acetyl-1,8-dihydroxy-3,6-dimethylnaphthalene: an
      outlier to current hydrogen bonding theory?
AB  - The environmental influence on the electronic character of two O-H...O hydrogen
      bonds in a beta-diketone, 2-acetyl-1,8-dihydroxy-3,6-dimethylnaphthalene, is
      studied by low-temperature synchrotron X-ray diffraction and high-level density
      functional theory (DFT) calculations. It is revealed that one of the hydrogen
      bonds is very strong, yet partial localization is found. This result is analyzed
      by atoms in molecules (AIM) theory and applying the source function. Model
      compounds, with less steric strain, reveal that the strong hydrogen bond is not
      merely a result of steric compression.

PMID- 17214473
TI  - Application of density functional theory and vibrational spectroscopy toward the
      rational design of ionic liquids.
AB  - Density functional theory methods in combination with vibrational spectroscopy
      are used to investigate possible variants of molecular structure of the ion pairs
      of several imidazolium-based ionic liquids (ILs). Multiple stable structures are
      determined with the anion positioned (a) near to the C2 atom of the imidazolium
      ring, (b) between N1 and C5, (c) between N3 and C4, and (d) between C4 and C5.
      Chloride and bromide anions in vacuum also occupy positions above or below the
      imidazolium ring, but in the condensed state these positions are destabilized. In
      comparison with the halides that almost equally occupy the positions (a-d),
      tetrafluoroborate and hexafluorophosphate anions strongly prefer position (a).
      The position and the type of the anion influence the conformation of the side
      chains bound to the imidazolium N1 atom, which are able to adopt in vacuum all
      usual staggered or eclipsed conformations, although in the liquid state some of
      the conformations are present only as minor forms if at all. Vibrations of the
      cations depend both on the conformational changes and on the association with the
      anion. The formation of the ion pairs influences mainly stretching and out-of
      plane vibrations of the imidazolium C-H groups and stretching vibrations of the
      perfluoroanions. Other modes of the ions retain their individuality and
      practically do not mix. This allows "interionic" vibrations to be separated and
      to regard the couple of the ions as an anharmonic oscillator. Such a model
      correlates the molecular structure of various ILs and their melting points
      without involving the energy of the interaction between the cations and anions
      but explains structure-melting point correlations on the grounds of quasy-elastic
      properties.

PMID- 17214474
TI  - A theoretical study of calcium monohydride, CaH: low-lying states and their
      permanent electric dipole moments.
AB  - Potential energy curves, energy parameters, and spectroscopic values for the X
      (2)Sigma(+), A (2)Pi, B (2)Sigma(+), a (4)Pi, and b (4)Sigma(+), states of CaH
      have been calculated using the multireference configuration interaction and
      coupled cluster levels of theory, while employing quantitative basis sets (of
      augmented quintuple-zeta quality) and taking also into account core/valence
      correlation and one-electron relativistic effects. For the ground (X (2)Sigma(+))
      and the first two following excited states (A (2)Pi, B (2)Sigma(+)) of CaH, the
      permanent electric dipole moments have been calculated. Our best finite field
      dipole moment of the A (2)Pi state of 2.425 D (upsilon = 0) is in very good
      agreement with the experimental literature value of 2.372(12) D. However, a
      discrepancy is observed in the dipole moment of the X (2)Sigma(+) state. Our most
      extensive calculation gives mu = 2.623 D (upsilon = 0), which is considerably
      smaller than the experimental value of mu = 2.94(16) D (upsilon = 0). Small van
      der Waals minima were found for both "repulsive" quartet states. Spectroscopic
      constants and energy parameters for all states are in remarkable agreement with
      available experimental values.

PMID- 17214475
TI  - The influence of electric field on the global and local reactivity descriptors:
      reactivity and stability of weakly bonded complexes.
AB  - The response of the global and local reactivity density-based descriptors
      (chemical potential, hardness, softness, Fukui function, and local softness) in
      the presence of external electric field has been studied for some of the simple
      prototype molecular systems. In addition to the analysis on the reactivity of
      these systems, the influence of the electric field on the interaction energy of
      the complexes formed by these systems has also been studied using the recently
      proposed semiquantitative model based on the local hard-soft acid-base principle.
      By using the inverse relationship between the global hardness and softness
      parameters, a simple relationship is obtained for the variation of hardness in
      terms of the Fukui function under the external electric field. It is shown that
      the increase in the hardness values for a particular system in the presence of
      external field does not necessarily imply that the reactivity of the system would
      be deactivated or vice versa.

PMID- 17214477
TI  - Structures and spectroscopic properties of bis(phthalocyaninato) yttrium and
      lanthanum complexes: theoretical study based on density functional theory
      calculations.
AB  - Density functional theory (DFT) calculations were carried out to describe the
      molecular structures, molecular orbitals, atomic charges, UV-vis absorption
      spectra, IR, and Raman spectra of bis(phthalocyaninato) rare earth(III) complexes
      M(Pc)(2) (M = Y, La) as well as their reduced products [M(Pc)(2)](-) (M = Y, La).
      Good consistency was found between the calculated results and experimental data.
      Reduction of the neutral M(Pc)(2) to [M(Pc)(2)]- induces the reorganization of
      their orbitals and charge distribution and decreases the inter-ring interaction.
      With the increase of ionic size from Y to La, the inter-ring distance of both the
      neutral and reduced double-decker complexes M(Pc)(2) and [M(Pc)(2)](-) (M = Y,
      La) increases, the inter-ring interaction and splitting of the Q bands decrease,
      and corresponding bands in the IR and Raman spectra show a red shift. The orbital
      energy level and orbital nature of the frontier orbitals are also described and
      explained in terms of atomic character. The present work, representing the first
      systemic DFT study on the bis(phthalocyaninato) yttrium and lanthanum complexes
      sheds further light on clearly understanding structure and spectroscopic
      properties of bis(phthalocyaninato) rare earth complexes.

PMID- 17214476
TI  - Theoretical and experimental studies of the spin trapping of inorganic radicals
      by 5,5-dimethyl-1-pyrroline N-oxide (DMPO). 2. Carbonate radical anion.
AB  - Previous studies have shown that the enzyme-mediated generation of carbonate
      radical anion (CO(3)(.-)) may play an important role in the initiation of
      oxidative damage in cells. This study explored the thermodynamics of CO(3)(.-)
      addition to 5,5-dimethyl-1-pyrroline N-oxide (DMPO) using density functional
      theory at the B3LYP/6-31+G(**)//B3LYP/6-31G* and B3LYP/6-311+G* levels with the
      polarizable continuum model to simulate the effect of the bulk dielectric effect
      of water on the calculated energetics. Theoretical data reveal that the addition
      of CO(3)(.-) to DMPO yields an O-centered radical adduct (DMPO-OCO2) as governed
      by the spin (density) population on the CO(3)(.-). Electron paramagnetic
      resonance spin trapping with the commonly used spin trap, DMPO, has been employed
      in the detection of CO(3)(.-). UV photolysis of H(2)O(2) and DMPO in the presence
      of sodium carbonate (Na(2)CO(3)) or sodium bicarbonate (NaHCO(3)) gave two
      species (i.e., DMPO-OCO(2) and DMPO-OH) in which the former has hyperfine
      splitting constant values of a(N) = 14.32 G, a(beta)-Eta = 10.68 G, and a(gamma
      H) = 1.37 G and with a shorter half-life compared to DMPO-OH. The origin of the
      DMPO-OH formed was experimentally confirmed using isotopically enriched
      H(2)(17)O(2) that indicates direct addition of HO(.) to DMPO. Theoretical studies
      on other possible pathways for the formation of DMPO-OH from DMPO-OCO(2) in
      aqueous solution and in the absence of free HO(.) such as in the case of
      enzymatically generated CO(3)(.-), show that the preferred pathway is via
      nucleophilc substitution of the carbonate moiety by H(2)O or HO(-). Nitrite
      formation has been observed as the end product of CO(3)(.-) trapping by DMPO and
      is partly dependent on the basicity of solution. The thermodynamic behavior of
      CO(3)(.-) in the aqueous phase is predicted to be similar to that of the
      hydroperoxyl (HO(2)(.)) radical.

PMID- 17214478
TI  - Electron binding capabilities of some silylenes having small singlet-triplet
      splittings or triplet ground states.
AB  - Several silyl and alkaline metal substituted silylenes have been investigated
      using the CAS-ACPF method in conjunction with the aug-cc-pVTZ basis sets.
      Silylsilylene and disilylsilylene are found to have singlet ground states with
      DeltaEST(-) values of 0.676 and 0.319 eV, respectively. The adiabatic ground
      state electron affinities are found to be 1.572 and 2.361 eV for HSiSiH(3) and
      Si(SiH(3))(2). respectively. Both silylenes possesses a stable 2A1 excited
      negative ion state, with respective adiabatic EA values of 0.037 and 1.000 eV. In
      contrast, all silylenes with at least one akaline metal substituent exhibit
      triplet neutral ground states. The metalated silylenes HSiLi, HSiNa, LiSiSiH(3),
      NaSiLi, SiLi(2), and SiNa(2) have adiabatic ground state EAs somewhat below 1 eV,
      but each of these negatively charged system possesses up to three bound excited
      negative ion states, some of which are dipole-bound states.

PMID- 17214479
TI  - Multicolor single-molecule spectroscopy with alternating laser excitation for the
      investigation of interactions and dynamics.
AB  - We have developed confocal multicolor single-molecule spectroscopy with optimized
      detection sensitivity on three spectrally distinct channels for the study of
      biomolecular interactions and FRET between more than two molecules. Using
      programmable acousto-optical devices as beamsplitter and excitation filter, we
      overcome some of the limitations of conventional multichroic beamsplitters and
      implement rapid alternation between three laser lines. This enables to visualize
      the synthesis of DNA three-way junctions on a single-molecule basis and to
      resolve seven stoichiometric subpopulations as well as to quantify FRET in the
      presence of competing energy transfer pathways. Furthermore, the ability to study
      correlated molecular movements by monitoring several distances within a
      biomolecular complex simultaneously is demonstrated.

PMID- 17214480
TI  - Early aggregation in prion peptide nanostructures investigated by nonlinear and
      ultrafast time-resolved fluorescence spectroscopy.
AB  - We report the characterization of early aggregates in the self-assembly of prion
      peptides using nonlinear and ultrafast time-resolved fluorescence spectroscopy.
      The dye-labeled peptide and dye/peptide guest-host systems were used to
      demonstrate the feasibility of the new approach. By measuring the two-photon
      absorption cross-section, small aggregates of the dye labeled peptide were
      characterized. Ultrafast time-resolved fluorescence anisotropy spectroscopy
      reveals the packing state (microenvironment) of the probes to be tightly
      associated with aggregates and associated with aggregation progression of the
      peptides. Fluorescence intensity decay shows a correlation with growth of
      aggregates having a high level of structured beta-sheet content. A new binding
      ligand Cascade Yellow shows promise for beta-sheet recognition of prion peptide
      nanostructures. These findings may have implications for in vivo studies of
      neurotoxic aggregates targeting with fluorescence markers. Also, these results
      may provide insight into molecular design of peptide-based nanomaterials.

PMID- 17214481
TI  - Formation of fractal-like structures driven by carbon nanotubes-based collapsed
      hollow capsules.
AB  - Carbon nanotubes (CNTs) based hollow capsules were obtained by degradation under
      acidic conditions of core-shell nanocomposites build up upon adsorption of
      multilayers of CNTs (shell) onto melamine-formaldehyde (MF) spheres (core). By
      evaporation of the dispersions obtained, polymeric fractal patterns from the
      degradation products of the MF core were formed onto silicon wafers. The proposed
      mechanism for the formation of these structures is based on the role of the
      capsules as arrangements of heterogeneities that facilitate the dewetting of the
      liquid polymeric films.

PMID- 17214482
TI  - Use of luminescence probing for the study of the interaction of
      polytitanasiloxane with trivalent rare earth ions.
AB  - Luminescent probing methods were employed to investigate the interaction of the
      Ti-O chains of polytitanasiloxane with europium ions in the mixture of ethanol
      and water. The UV-vis absorption, the luminescence intensity, and the
      luminescence lifetimes of the Eu3+ ions in PTS solutions were all found to
      increase with the increase of TBT/TEOS molar ratio. The results indicated that
      the incorporation of TBT can result in the increase of absorption energy of the
      Ti-O group by near-UV excitation and in the increase of energy transfer to the
      metal ion, and that the Ti-O chains due to the site binding of Eu3+ ions can
      expel six to nine solvent molecules from the first coordination solvation shell
      of the ion. The investigation of the energy transfer from europium to neodymium
      ions in polytitanasiloxane solutions revealed the formation of aggregates
      consisting of seven rare earth ions (together with the polytitanasiloxane
      countercharges).

PMID- 17214483
TI  - Dynamic scaling of polymer gels comprising nanoparticles.
AB  - We present dynamic light scattering (DLS) measurements of soft poly(methyl
      methacrylate) (PMMA) and polyacrylamide (PA) polymer gels prepared with trapped
      bodies (latex spheres or magnetic nanoparticles). We show that the anomalous
      diffusivity of the trapped particles can be analyzed in terms of a fractal
      Gaussian network gel model for the entire time range probed by DLS technique.
      This model is a generalization of the Rouse model for linear chains extended for
      structures with power law network connectivity scaling, which includes both
      percolating and uniform bulk gel limits. For a dilute dispersion of strongly
      scattering particles trapped in a gel, the scattered electric field correlation
      function at small wavevector ideally probes self-diffusion of gel portions
      imprisoning the particles. Our results show that the time-dependent diffusion
      coefficients calculated from the correlation functions change from a free
      diffusion regime at short times to an anomalous subdiffusive regime at long times
      (increasingly arrested displacement). The characteristic time of transition
      between these regimes depends on scattering vector as approximately q(-2), while
      the time decay power exponent tends to the value expected for a bulk network at
      small q. The diffusion curves for all scattering vectors and all samples were
      scaled to a single master curve.

PMID- 17214484
TI  - Nonequilibrium liquid crystalline layered phase stabilized by light.
AB  - The ability of light to alter/stabilize a particular thermodynamic phase is a
      power tool to investigate condensed matter from a new dimension. This field of
      photoinduced phase transitions is currently an important area of research. Being
      elastically soft and having subtle changes between its many phases a liquid
      crystal material is an attractive medium to investigate such light-driven phase
      transitions. The attraction is partly due to the large birefringence changes
      accompanying these transitions that are useful in developing photonic devices. In
      all of the cases reported to date, the photoinduced transition always leads to a
      phase that in any case exists in the thermal cycle. Recently we reported the
      first exception to such an established phenomenon (Adv. Mater. 2005, 17, 2086).
      The guest-host ternary mixture consisting of the photoactive azobenzene guest
      molecules does not exhibit smectic A phase in the absence of UV radiation.
      However, the smectic A phase is induced and stabilized only in the presence of UV
      light. In this paper, we map out hitherto unexplored temperature versus UV
      intensity phase diagrams for various mixtures, which illustrate that light
      mimics, in a limited sense, the role of a thermodynamic parameter such as, for
      example, pressure. The threshold UV intensity required to photodrive the
      appearance of the smectic A phase is seen to have a strong concentration
      dependence. Our studies also suggest the possibility of observing a double
      critical point by employing the UV intensity as a fine-tuning parameter.

PMID- 17214485
TI  - Morphologies and bridging properties of graft copolymers.
AB  - Morphologies and bridging properties of graft copolymers in the bulk state were
      studied by using a real-space algorithm of self-consistent field theory in two
      dimensions. The phase transition from cylindrical to lamellar phase can be
      triggered by changing the position of graft points and the number of branches.
      The fraction of bridged conformation, f(bridge), shows a tendency to decrease
      with increasing the length of free end blocks, tau1, and the number of branches,
      m. The value of f(bridge) has a discontinuous drop when the transition from
      cylindrical to lamellar phase takes place. The relationship between m and the
      number of bridged chains per unit area, nb, which is associated with the
      mechanical properties of copolymers, was also examined. It was found that nb
      increases with increasing m in the cylindrical phase. However, in the lamellar
      phase, nb decreases when m increases. It is proposed that the position of graft
      points and the number of branches are two important parameters for material
      design.

PMID- 17214486
TI  - Microstructure design of nanoporous TiO2 photoelectrodes for dye-sensitized solar
      cell modules.
AB  - The optimization of dye-sensitized solar cells, especially the design of
      nanoporous TiO2 film microstructure, is an urgent problem for high efficiency and
      future commercial applications. However, up to now, little attention has been
      focused on the design of nanoporous TiO2 microstructure for a high efficiency of
      dye-sensitized solar cell modules. The optimization and design of TiO2
      photoelectrode microstructure are discussed in this paper. TiO2 photoelectrodes
      with three different layers, including layers of small pore size films, larger
      pore size films, and light-scattering particles on the conducting glass with the
      desirable thickness, were designed and investigated. Moreover, the photovoltaic
      properties showed that the different porosities, pore size distribution, and BET
      surface area of each layer have a dramatic influence on short-circuit current,
      open-circuit voltage, and fill factor of the modules. The optimization and design
      of TiO2 photoelectrode microstructure contribute a high efficiency of DSC
      modules. The photoelectric conversion efficiency around 6% with 15 x 20 cm2
      modules under illumination of simulated AM1.5 sunlight (100 mW/cm2) and 40 x 60
      cm2 panels with the same performance tested outdoor have been achieved by our
      group.

PMID- 17214487
TI  - Tailoring porous silica films through supercritical carbon dioxide processing of
      fluorinated surfactant templates.
AB  - The tailoring of porous silica thin films synthesized using
      perfluoroalkylpyridinium chloride surfactants as templating agents is achieved as
      a function of carbon dioxide processing conditions and surfactant tail length and
      branching. Well-ordered films with 2D hexagonal close-packed pore structure are
      obtained from sol-gel synthesis using the following cationic fluorinated
      surfactants as templates: 1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro
      octyl)pyridinium chloride (HFOPC), 1-(3,3,4,4,5,5,6,6,7,8,8,8-dodecafluoro-7
      trifluoromethyl -octyl)pyridinium chloride (HFDoMePC), and 1
      (3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-decyl)pyridinium chloride
      (HFDePC). Processing the sol-gel film with CO2 (69-172 bar, 25 and 45 degrees C)
      immediately after coating results in significant increases in pore diameter
      relative to the unprocessed thin films (increasing from 20% to 80% depending on
      surfactant template and processing conditions). Pore expansion increases with CO2
      processing pressure, surfactant tail length, and surfactant branching. The
      varying degree of CO2 induced expansion is attributed to the solvation of the
      "CO2-philic" fluorinated tail and is interpreted from interfacial behavior of
      HFOPC, HFDoMePC, and HFDePC at the CO2-water interface.

PMID- 17214488
TI  - Rheological properties of a telechelic associative polymer in the presence of
      alpha- and methylated beta-cyclodextrins.
AB  - The viscosity of hydrophobic ethoxylated urethane (HEUR) solution decreased in
      the presence of alpha-CD or m-beta-CD; however their interactions were quite
      different. When the alpha-CD/hydrophobe molar ratio exceeded 5.0, the viscosity
      was close to that of a PEO solution of similar molecular weight. Oscillatory
      shear indicated that the mechanically active chains in HEUR solution decreased
      with the addition of alpha-CD. This agreed with the hypothesis that alpha-CD
      formed an inclusion complex with the hydrophobic moiety of the HEUR polymer,
      thereby destroying the transient hydrophobic associative network. The
      viscosity/temperature relationship of the alpha-CD/HEUR system (for HEUR with 70%
      of the PEO chains capped at both ends) did not obey the Arrhenius relationship
      for alpha-CD/hydrophobe molar ratio in the range 0.8-5.0. The low shear viscosity
      increased with increasing temperature at molar ratio of 1.0, and this was
      attributed to the competitive complexation of the alpha-CD/hydrophobe and the
      alpha-CD/PEO chain. Increasing temperature favored alpha-CD/PEO complexation.
      Comparison between the behavior of alpha-CD/HEUR and m-beta-CD/HEUR resulting
      from the different binding characteristics was discussed.

PMID- 17214489
TI  - A model system to study the insertion of cholesterol into a phospholipid
      monolayer.
AB  - Colloidal probe atomic force microscopy (AFM) was used to study the interaction
      between a surface bearing tethered cholesterol groups and an egg
      phosphatidylcholine (egg-PC) monolayer. The cholesterol bearing surface was
      comprised of a mixed self-assembled monolayer comprised of O-cholesteryl N-(8'
      mecapto-3',6'-dioxaoctyl)carbamate (CPEO3) molecules and beta-mercaptoethanol
      formed on a 20 mum diameter gold-coated silica particle. The egg-PC monolayer was
      adsorbed onto an octadecylthiol monolayer formed on template-stripped gold. The
      force between the surfaces, as a function of separation, was measured for surface
      concentrations of CPEO3 from 0 to 100 mol %. At all concentrations there was a
      long-range repulsive double-layer force due to weak surface charges. At surface
      concentrations of CPEO3 from 1 to 29 mol % the interaction on the approach of the
      surfaces showed a maximum in the repulsive force, followed by a small (2-5 nm)
      jump into a force minimum corresponding to adhesion of the surfaces. On
      separation, a normalized pull-off force of 1.0-1.6 mN m(-1) was measured. Over
      the same concentration range, the calculated interaction energy per CPEO3
      molecule decreased from 1.1 +/- 0.2 kT to 0.04 kT. At surface concentrations of
      35 mol % and above there was no reproducible adhesion between the cholesterol
      bearing surface and the phospholipid monolayer. We attribute the occurrence of
      short-range attraction and adhesion in the 1-29 mol % regime to the insertion of
      (some) cholesterol groups into the phospholipid monolayer. At higher surface
      concentrations the efficiency of insertion is reduced due to steric effects. We
      discuss the experimental results in the light of the energetics of the insertion
      of a cholesterol molecule into a lipid bilayer.

PMID- 17214490
TI  - Evolution of intermolecular structure and dynamics in supercritical carbon
      dioxide with pressure: an ab initio molecular dynamics study.
AB  - The effect of pressure on supercritical carbon dioxide (scCO2) has been
      characterized by using Car-Parrinello molecular dynamics simulations. Structural
      and dynamical properties along an isotherm of 318.15 K and at pressures ranging
      from 190 to 5000 bar have been obtained. Intermolecular pair correlation
      functions and three-dimensional atomic probability density map calculations
      indicate that the local environment of a central CO2 molecule becomes more
      structured with increasing pressure. The closest neighbors are predominantly
      oriented in a distorted T-shaped geometry while neighbors separated by larger
      distances are likely oriented in a slipped parallel arrangement. The structure of
      scCO2 at high densities has been compared with that of crystalline CO2. The
      probability distributions of intramolecular distances narrow down with increasing
      pressure. A marginal but non-negligible effect of pressure on the instantaneous
      intramolecular OCO angle is observed, lending credence to the idea that
      intermolecular interactions between CO2 molecules in an inhomogeneous near
      neighbor environment could contribute to the observed instantaneous molecular
      dipole moment. The extent of deviation from a perfect linear geometry of the
      carbon dioxide molecule decreases with increasing pressure. Time constants
      derived from reorientational time correlation functions of the molecular backbone
      compare well with experimental data. Within the range of thermodynamic conditions
      explored here, no significant changes are observed in the frequencies of
      intramolecular vibrational modes. However, a blue shift is observed in the low
      frequency cage rattling mode with increasing pressure.

PMID- 17214491
TI  - Novel corresponding-states principle approach for the equation of state of
      isotopologues: H2(18)O as an example.
AB  - The corresponding-states principle (CSP) has been considered for the development
      of the equations of state (EOS) of minor isotopologues that are usually unknown.
      We demonstrate that, for isotopologues of a given molecular fluid, a general
      extended multi-parameter corresponding-states EOS can be reduced to the three
      parameter EOS, utilizing the critical parameters (temperature and density) and
      Pitzer's acentric factor as correlation parameters. Appropriate general CSP
      mathematical formalism and equations for constructing the EOS of minor
      isotopologues are described in detail. The formalism and equations were applied
      to isotopologues of water and demonstrated that the isotopic effect on the
      critical parameters and the acentric factor of H(2)(18)O can be successfully
      calculated from the EOS of H2O and experimental data on the isotope effects
      (liquid-vapor isotope fractionation factor and molar volume isotope effect). We
      have also shown that the experimental data on the vapor pressure isotope effect
      (VPIE) for 18O-substituted water are inconsistent within the framework of
      thermodynamics with the liquid-vapor oxygen isotope fractionation factor. The
      novel approach of CSP to isotopologues developed in this study creates a new
      opportunity for constructing the EOS of minor isotopologues for many other
      molecular fluids.

PMID- 17214492
TI  - Instabilities in block copolymer films induced by compressible solvents.
AB  - We combine a simple lattice-gas model for fluid mixtures along with polymer mean
      field theory for block copolymer melts to study the stability of thin films of
      diblock copolymers in the presence of compressible fluid solvents. Using a free
      energy analysis, the stable and unstable thicknesses of a copolymer thin film are
      obtained for given solvent conditions. Our results suggest that the interplay
      between confinement, the compressibility of the solvent, and its selectivity to
      polymer component can lead to significant changes on the ordering and stability
      of the diblock copolymer thin films. Our results are in qualitative agreement
      with recent experimental results.

PMID- 17214493
TI  - Single-ion solvation free energies and the normal hydrogen electrode potential in
      methanol, acetonitrile, and dimethyl sulfoxide.
AB  - The division of thermodynamic solvation free energies of electrolytes into
      contributions from individual ionic constituents is conventionally accomplished
      by using the single-ion solvation free energy of one reference ion,
      conventionally the proton, to set the single-ion scales. Thus, the determination
      of the free energy of solvation of the proton in various solvents is a
      fundamental issue of central importance in solution chemistry. In the present
      article, relative solvation free energies of ions and ion-solvent clusters in
      methanol, acetonitrile, and dimethyl sulfoxide (DMSO) have been determined using
      a combination of experimental and theoretical gas-phase free energies of
      formation, solution-phase reduction potentials and acid dissociation constants,
      and gas-phase clustering free energies. Applying the cluster pair approximation
      to differences between these relative solvation free energies leads to values of 
      263.5, -260.2, and -273.3 kcal/mol for the absolute solvation free energy of the
      proton in methanol, acetonitrile, and DMSO, respectively. The final absolute
      proton solvation free energies are used to assign absolute values for the normal
      hydrogen electrode potential and the solvation free energies of other single ions
      in the solvents mentioned above.

PMID- 17214494
TI  - Stereodifferentiating drug-biomolecule interactions in the triplet excited state:
      studies on supramolecular carprofen/protein systems and on carprofen-tryptophan
      model dyads.
AB  - Stereoselective interaction between a chiral nonsteroidal antiinflammatory drug,
      namely carprofen (CP), and human serum albumin (HSA) was studied, and the results
      were compared with those obtained with model dyads. In the presence of albumin
      the same triplet-triplet transition was detected for both CP stereoisomers;
      however, time-resolved measurements revealed a remarkable stereodifferentiation
      in the CP/HSA interaction. For each stereoisomer, the decay dynamics evidenced
      the presence of two components with different lifetimes that can be correlated
      with complexation of CP to the two possible albumin binding sites (site I and
      site II). This assignment was confirmed by using ibuprofen, a site II displacer.
      Thus, the shorter lived components, for which stereodifferentiation was more
      important (tauR/tauS ca. 4), were ascribed to the CP triplet state in site I; the
      lifetime shortening can be attributed to electron-transfer quenching by the only
      tryptophan (Trp) of the protein. Laser flash photolysis of model dyads containing
      covalently linked CP and Trp revealed formation of the expected Trp radical
      cation, providing support for such a mechanism. Moreover, significant
      stereodifferentiation was observed between the (R)- and (S)-CP-Trp dyads. In the
      case of CP/HSA complexes, as well as in the model compounds, the
      stereodifferentiation detected in the decays is in good agreement with that
      observed in the formation of the only CP photoproduct, resulting from a
      photodehalogenation process. Moreover, stereodifferentiation was also found to
      occur for the photobinding of CP to the protein.

PMID- 17214495
TI  - Impact of pyrophosphate and O-ethyl-substituted pyrophosphate groups on DNA
      structure.
AB  - Design of novel DNA probes to inhibit specific repair pathways is important for
      basic science applications and for use as therapeutic agents. As shown
      previously, single pyrophosphate (PP) and O-ethyl-substituted pyrophosphate (SPP)
      modifications can inhibit the DNA glycosylase activities on damaged DNA. To
      understand the structural basis of this inhibition, the influence of the PP and
      SPP internucleotide groups on the helical parameters and geometry of a double
      stranded DNA was studied by using molecular modeling tools including molecular
      dynamics and quantum mechanical-molecular mechanical (QM/MM) approaches. Native
      and locally modified PP- and SPP-containing DNA duplexes of dodecanucleotide
      d(C1G2C3G4A5A6T7T8C9G10C11G12) were simulated in aqueous solution. The energies
      and forces were computed by using the PBE0/6-31+G** approach in the QM part and
      the AMBER force-field parameters in the MM part. Analysis of the local base-pair
      helical parameters, internucleotide distances, and overall global structure at
      the located stationary points revealed a close similarity of the initial and
      modified duplexes, with only torsion angles of the main chain being altered in
      the vicinity of introduced chemical modification. Results show that the PP and
      SPP groups are built into a helix structure without elongation of the
      internucleotide distance due to flipping-out of phosphate group from the sugar
      phosphate backbone. The mechanism of such embedding has only a minor impact on
      the base pairs stacking and Watson-Crick interactions. Biochemical studies
      revealed that the PP and SPP groups immediately 5', but not 3', to the 8
      oxoguanosine (8oxodG) inhibit translesion synthesis by a DNA polymerase in vitro.
      These results suggest that subtle perturbations of the DNA backbone conformation
      influence processing of base lesions.

PMID- 17214496
TI  - Density functional theory investigation on the mechanism of the hepatitis delta
      virus ribozyme.
AB  - Density functional theory methods have been used to investigate the hepatitis
      delta virus (HDV) ribozyme and its catalyzed phosphodiester cleavage. In
      particular, the effects of the environment's polarity and/or specific hydrogen
      bond interactions on the proton affinity of the active site cytosine's N3 ring
      center have been considered. In addition, the basicities of possible hydrated
      Mg2+ ion species were also examined. The mechanism previously proposed for the
      HDV ribozyme in which the active site cytosine (C75) is protonated and thus acts
      as an acid while the Mg2+ species acts as the complementary base was then
      investigated. The possible role of tautomerization of C75 is also discussed.

PMID- 17214497
TI  - Ab initio study of the two-photon circular dichroism in chiral natural amino
      acids.
AB  - Two-photon circular dichroism spectra calculated within an origin-invariant
      density functional theory approximation in the absorption region where the lowest
      electronic excited states appear are presented for all 19 essential amino acids
      in the gas phase. A comparison of intensities and characteristic features is made
      with the corresponding two-photon absorption and one-photon circular dichroism
      spectra for each species. Also, the contributions of the electric dipole,
      magnetic dipole, and electric quadrupole transitions to the rotational strengths
      are analyzed in some detail. The remarkable fingerprinting capabilities of the
      two-photon circular dichroism spectroscopy are highlighted.

PMID- 17214498
TI  - Effects of bridge ions, DNA species, and developing temperature on flat-lying DNA
      monolayers.
AB  - Recently, we have successfully constructed flat-lying DNA monolayers on a mica
      surface (J. Phys. Chem. B 2006, 110, 10792-10798). In this work, the effects of
      various factors including bridge ions, DNA species, and developing temperature on
      the configuration of DNA monolayers have been investigated by atomic force
      microscopy (AFM) in detail. AFM results show that the species of bridge ions and
      developing temperature play a crucial role during the formation process. For
      example, the divalent cation Zn2+ resulted in many DNA chains stuck side by side
      in the monolayers due to the strong interactions between it and DNA's bases or
      the mica surface. Most DNA chain's conglutinations disappeared when the
      developing temperature was higher than 40 degrees C. Cd2+ and Ca2+ produced more
      compact DNA monolayers with some obvious aggregations, especially for the DNA
      monolayers constructed by using Ca2+ as the bridge ion. Co2+ produced well
      ordered, flat-lying DNA monolayers similar to that of Mg2+. Furthermore, it was
      found that the flat-lying DNA monolayers could still form on a mica surface when
      plasmid DNA pBR 322 and linear DNA pBR 322/Pst I were used as the DNA source.
      Whereas, it was hard to form DNA monolayers on a (3-aminopropyl)triethoxysilane
      mica surface because the strong interactions between DNA and substrate prevented
      the lateral movement of DNA molecules. These results suggested that the
      appropriate interactions between divalent cations and DNA or mica surface were
      important for the formation of flat-lying DNA monolayers. The obtained
      information is a necessary supplement to our previous studies on the formation
      kinetics of such monolayers and may be useful for practical application of the
      monolayers and further theoretical studies.

PMID- 17214499
TI  - Direct electron transfer kinetics in horseradish peroxidase electrocatalysis.
AB  - The study of direct electron transfer between enzymes and electrodes is
      frequently hampered by the small fraction of adsorbed proteins that remains
      electrochemically active. Here, we outline a strategy to overcome this
      limitation, which is based on a hierarchical analysis of steady-state
      electrocatalytic currents and the adoption of the "binary activity" hypothesis.
      The procedure is illustrated by studying the electrocatalytic response of
      horseradish peroxidase (HRP) adsorbed on graphite electrodes as a function of
      substrate (hydrogen peroxide) concentration, electrode potential, and solution
      pH. Individual contributions of the rates of substrate/enzyme reaction and of the
      electrode/enzyme electron exchange to the observed catalytic currents were
      disentangled by taking advantage of their distinct dependence on substrate
      concentration and electrode potential. In the absence of nonturnover currents,
      adoption of the "binary activity" hypothesis provided values of the standard
      electron-transfer rate constant for reduction of HRP Compound II that are similar
      to those reported previously for reduction of cytochrome c peroxidase Compound
      II. The variation of the catalytic currents with applied potential was analyzed
      in terms of the non-adiabatic Marcus-DOS electron transfer theory. The
      availability of a broad potential window, where catalytic currents could be
      recorded, facilitates an accurate determination of both the reorganization energy
      and the maximum electron-transfer rate for HRP Compound II reduction. The
      variation of these two kinetic parameters with solution pH provides some
      indication of the nature and location of the acid/base groups that control the
      electronic exchange between enzyme and electrode.

PMID- 17214500
TI  - In situ monitoring of the synthesis of a pyranine-substituted phthalonitrile
      derivative via the steady-state fluorescence technique.
AB  - A new approach based on fluorescence quenching of a chromophore, pyranine (8
      hydroxypyrene-1,3,6-trisulfonic acid, trisodium salt, POH), was established for
      monitoring the synthesis of the pyranine-substituted phthalonitrile derivative
      POPht. 4-Nitrophthalonitrile binds to the POH through nitro elimination, by means
      of a nucleophilic aromatic substitution reaction in a basic medium, and forms
      phthalonitrile (Pht) bearing deprotonated POH units, Pht + POH --> POPht. This
      binding process results in a considerable blue shift (from 515 to 430 nm) in the
      fluorescence emission spectra of POH. Besides, the fluorescence intensities of
      unreacted pyranines and POPht molecules in the reacting mixture decrease as they
      are quenched by nitrite appearing as one of the byproducts. POH, therefore, acts
      as both an aromatic substituent for Pht and a fluorescence probe for monitoring
      the substitution reaction. Thus, the change in the fluorescence spectra
      introduces a novel method for in situ monitoring of the synthesis of the
      phthalonitrile derivative POPht. This new material may have a potential to
      synthesize the phthalocyanine having an enhanced fluorescence property and
      solubility in an aqua medium that would result in a desired candidate molecule in
      many applications of phthalocyanines.

PMID- 17214501
TI  - Density functional theory methods as powerful tools to elucidate amino acid
      oxidation mechanisms. A case study on methionine model peptide.
AB  - The amino acid oxidation mechanism has been a research focus in recent years.
      Although various experimental techniques have been employed to address the
      problem, it is still a great challenge to identify the oxidation intermediates of
      amino acids. To explore the potential of theoretical methods in helping
      elucidating amino acid oxidation mechanisms, one-electron oxidation of a
      methionine model peptide (N-acetylmethionine amide) was investigated by density
      functional theory (DFT; including TD-DFT) calculations. The theoretical results
      not only testified the experimentally identified oxidation mechanisms of the
      peptide to a large extent but also revealed the contribution of protonated
      species to the peptide oxidation. All of these findings strongly suggest that DFT
      methodology has great potential in investigating amino acid oxidation mechanisms.

PMID- 17214503
TI  - Pandemic influenza: risk of multiple introductions and the need to prepare for
      them.

PMID- 17214504
TI  - Relationship between funding source and conclusion among nutrition-related
      scientific articles.
AB  - BACKGROUND: Industrial support of biomedical research may bias scientific
      conclusions, as demonstrated by recent analyses of pharmaceutical studies.
      However, this issue has not been systematically examined in the area of nutrition
      research. The purpose of this study is to characterize financial sponsorship of
      scientific articles addressing the health effects of three commonly consumed
      beverages, and to determine how sponsorship affects published conclusions.
      METHODS AND FINDINGS: Medline searches of worldwide literature were used to
      identify three article types (interventional studies, observational studies, and
      scientific reviews) about soft drinks, juice, and milk published between 1
      January, 1999 and 31 December, 2003. Financial sponsorship and article
      conclusions were classified by independent groups of coinvestigators. The
      relationship between sponsorship and conclusions was explored by exact tests and
      regression analyses, controlling for covariates. 206 articles were included in
      the study, of which 111 declared financial sponsorship. Of these, 22% had all
      industry funding, 47% had no industry funding, and 32% had mixed funding. Funding
      source was significantly related to conclusions when considering all article
      types (p = 0.037). For interventional studies, the proportion with unfavorable
      conclusions was 0% for all industry funding versus 37% for no industry funding (p
      = 0.009). The odds ratio of a favorable versus unfavorable conclusion was 7.61
      (95% confidence interval 1.27 to 45.73), comparing articles with all industry
      funding to no industry funding. CONCLUSIONS: Industry funding of nutrition
      related scientific articles may bias conclusions in favor of sponsors' products,
      with potentially significant implications for public health.

PMID- 17214505
TI  - Does industry sponsorship undermine the integrity of nutrition research?

PMID- 17214506
TI  - Schistosomiasis mansoni: novel chemotherapy using a cysteine protease inhibitor.
AB  - BACKGROUND: Schistosomiasis is a chronic, debilitating parasitic disease
      infecting more than 200 million people and is second only to malaria in terms of
      public health importance. Due to the lack of a vaccine, patient therapy is
      heavily reliant on chemotherapy with praziquantel as the World Health
      Organization-recommended drug, but concerns over drug resistance encourage the
      search for new drug leads. METHODS AND FINDINGS: The efficacy of the vinyl
      sulfone cysteine protease inhibitor K11777 was tested in the murine model of
      schistosomiasis mansoni. Disease parameters measured were worm and egg burdens,
      and organ pathology including hepato- and splenomegaly, presence of parasite egg
      induced granulomas in the liver, and levels of circulating alanine
      aminotransferase activity as a marker of hepatocellular function. K11777 (25
      mg/kg twice daily [BID]), administered intraperitoneally at the time of parasite
      migration through the skin and lungs (days 1-14 postinfection [p.i.]), resulted
      in parasitologic cure (elimination of parasite eggs) in five of seven cases and a
      resolution of other disease parameters. K11777 (50 mg/kg BID), administered at
      the commencement of egg-laying by mature parasites (days 30-37 p.i.), reduced
      worm and egg burdens, and ameliorated organ pathology. Using protease class
      specific substrates and active-site labeling, one molecular target of K11777 was
      identified as the gut-associated cathepsin B1 cysteine protease, although other
      cysteine protease targets are not excluded. In rodents, dogs, and primates,
      K11777 is nonmutagenic with satisfactory safety and pharmacokinetic profiles.
      CONCLUSIONS: The significant reduction in parasite burden and pathology by this
      vinyl sulfone cysteine protease inhibitor validates schistosome cysteine
      proteases as drug targets and offers the potential of a new direction for
      chemotherapy of human schistosomiasis.

PMID- 17214507
TI  - Large-scale mapping and validation of Escherichia coli transcriptional regulation
      from a compendium of expression profiles.
AB  - Machine learning approaches offer the potential to systematically identify
      transcriptional regulatory interactions from a compendium of microarray
      expression profiles. However, experimental validation of the performance of these
      methods at the genome scale has remained elusive. Here we assess the global
      performance of four existing classes of inference algorithms using 445
      Escherichia coli Affymetrix arrays and 3,216 known E. coli regulatory
      interactions from RegulonDB. We also developed and applied the context likelihood
      of relatedness (CLR) algorithm, a novel extension of the relevance networks class
      of algorithms. CLR demonstrates an average precision gain of 36% relative to the
      next-best performing algorithm. At a 60% true positive rate, CLR identifies 1,079
      regulatory interactions, of which 338 were in the previously known network and
      741 were novel predictions. We tested the predicted interactions for three
      transcription factors with chromatin immunoprecipitation, confirming 21 novel
      interactions and verifying our RegulonDB-based performance estimates. CLR also
      identified a regulatory link providing central metabolic control of iron
      transport, which we confirmed with real-time quantitative PCR. The compendium of
      expression data compiled in this study, coupled with RegulonDB, provides a
      valuable model system for further improvement of network inference algorithms
      using experimental data.

PMID- 17214510
TI  - Analysis of boron distribution in vivo for boron neutron capture therapy using
      two different boron compounds by secondary ion mass spectrometry.
AB  - The efficiency of boron neutron capture therapy (BNCT) for malignant gliomas
      depends on the selective and absolute accumulation of (10)B atoms in tumor
      tissues. Only two boron compounds, BPA and BSH, currently can be used clinically.
      However, the detailed distributions of these compounds have not been determined.
      Here we used secondary ion mass spectrometry (SIMS) to determine the histological
      distribution of (10)B atoms derived from the boron compounds BSH and BPA. C6
      tumor-bearing rats were given 500 mg/kg of BPA or 100 mg/kg of BSH
      intraperitoneally; 2.5 h later, their brains were sectioned and subjected to
      SIMS. In the main tumor mass, BPA accumulated heterogeneously, while BSH
      accumulated homogeneously. In the peritumoral area, both BPA and BSH accumulated
      measurably. Interestingly, in this area, BSH accumulated distinctively in a
      diffuse manner even 800 microm distant from the interface between the main tumor
      and normal brain. In the contralateral brain, BPA accumulated measurably, while
      BSH did not. In conclusion, both BPA and BSH each have advantages and
      disadvantages. These compounds are considered to be essential as boron delivery
      agents independently for clinical BNCT. There is some rationale for the
      simultaneous use of both compounds in clinical BNCT for malignant gliomas.

PMID- 17214508
TI  - Intermolecular failure of L-type Ca2+ channel and ryanodine receptor signaling in
      hypertrophy.
AB  - Pressure overload-induced hypertrophy is a key step leading to heart failure. The
      Ca(2+)-induced Ca(2+) release (CICR) process that governs cardiac contractility
      is defective in hypertrophy/heart failure, but the molecular mechanisms remain
      elusive. To examine the intermolecular aspects of CICR during hypertrophy, we
      utilized loose-patch confocal imaging to visualize the signaling between a single
      L-type Ca(2+) channel (LCC) and ryanodine receptors (RyRs) in aortic stenosis rat
      models of compensated (CHT) and decompensated (DHT) hypertrophy. We found that
      the LCC-RyR intermolecular coupling showed a 49% prolongation in coupling
      latency, a 47% decrease in chance of hit, and a 72% increase in chance of miss in
      DHT, demonstrating a state of "intermolecular failure." Unexpectedly, these
      modifications also occurred robustly in CHT due at least partially to decreased
      expression of junctophilin, indicating that intermolecular failure occurs prior
      to cellular manifestations. As a result, cell-wide Ca(2+) release, visualized as
      "Ca(2+) spikes," became desynchronized, which contrasted sharply with unaltered
      spike integrals and whole-cell Ca(2+) transients in CHT. These data suggested
      that, within a certain limit, termed the "stability margin," mild intermolecular
      failure does not damage the cellular integrity of excitation-contraction
      coupling. Only when the modification steps beyond the stability margin does
      global failure occur. The discovery of "hidden" intermolecular failure in CHT has
      important clinical implications.

PMID- 17214511
TI  - Secondary carcinogenesis in patients treated with radiation: a review of data on
      radiation-induced cancers in human, non-human primate, canine and rodent
      subjects.
AB  - Concern for risk of radiation-induced cancer is growing with the increasing
      number of cancer patients surviving long term. This study examined data on
      radiation transformation of mammalian cells in vitro and on the risk of an
      increased cancer incidence after irradiation of mice, dogs, monkeys, atomic bomb
      survivors, occupationally exposed persons, and patients treated with radiation.
      Transformation of cells lines in vitro increased linearly with dose from
      approximately 1 to approximately 4-5 Gy. At <0.1 Gy, transformation was not
      increased in all studies. Dose-response relationships for cancer incidence varied
      with mouse strain, gender and tissue/organ. Risk of cancer in Macaca mulatta was
      not raised at 0.25-2.8 Gy. From the atomic bomb survivor study, risk is accepted
      as increasing linearly to 2 Sv for establishing exposure standards. In irradiated
      patients, risk of cancer increased significantly from 1 to 45 Gy (a low to a high
      dose level) for stomach and pancreas, but not for bladder and rectum (1-60 Gy) or
      kidney (1-15 Gy). Risk for several organs/tissues increased substantially at
      doses far above 2 Gy. There is great heterogeneity in risk of radiation
      associated cancer between species, strains of a species, and organs within a
      species. At present, the heterogeneity between and within patient populations of
      virtually every parameter considered in risk estimation results in substantial
      uncertainty in quantification of a general risk factor. An implication of this
      review is that reduced risks of secondary cancer should be achieved by any
      technique that achieved a dose reduction down to approximately [corrected] 0.1
      Gy, i.e. dose to tissues distant from the target. The proportionate gain should
      be greatest for dose decrement to less than 2 Gy.

PMID- 17214512
TI  - Accurate electron inelastic cross sections and stopping powers for liquid water
      over the 0.1-10 keV range based on an improved dielectric description of the
      Bethe surface.
AB  - Electron inelastic cross sections and stopping powers for liquid water over the
      0.1-10 keV range are presented based on a recently developed dielectric response
      model for liquid water (D. Emfietzoglou, F. Cucinotta and H. Nikjoo, Radiat. Res.
      164, 202-211, 2005) that is consistent with the experimental data over the whole
      energy-momentum plane. Both exchange and second-order Born corrections are
      included in a material-specific way using the dielectric functions of liquid
      water. The numerical results are fitted by simple analytic functions to
      facilitate their further use. Compared to previous studies, differential cross
      sections are shifted toward smaller energy losses resulting in smaller inelastic
      and stopping cross sections with differences reaching, on average, the
      approximately 20% and approximately 50% level, respectively. Contrary to higher
      energies, it is shown that the dispersion model for the momentum dependence of
      the dielectric functions (Bethe ridge) is as important as the optical model used.
      Within the accuracy of the experimental data (a few percent) upon which our
      dielectric model is based, the calculations are "exact" to first order, while the
      uncertainty of the results beyond first order is estimated at the 5-10% level.
      The present work overcomes the limitations of Bethe's theory at low energies by a
      self-consistent account of inner-shell effects and may serve to extend the ICRU
      electron stopping power database for liquid water down to 100 eV with a level of
      uncertainty similar to that for the higher-energy values.

PMID- 17214513
TI  - Collapse of skin antioxidant status during the subacute period of cutaneous
      radiation syndrome: a case report.
AB  - This case report describes a patient suffering from accidental cutaneous
      radiation syndrome. Clinical symptoms were characterized by the presence of moist
      epidermal denudation over approximately 8% of the body surface without signs of
      necrosis 88 days after radiation exposure. The skin transcriptional profile was
      obtained and provides a comprehensive overview of the changes in gene expression
      associated with skin wound healing after irradiation. In particular, our data
      show a specific set of genes, i.e. SOD1, GPX1, TDX1, TDX2 and HSP60, implicated
      in the redox control of normal skin repair after radiation exposure, whereas HOX1
      and HOX2 were involved in the pathological skin repair. A reduction in the
      antioxidant capacity of the irradiated tissue concomitant with a progressive
      establishment of an uncontrolled inflammatory response was noted. Our data
      corroborate the hypothesis that ROS modulation is a key element of the healing
      response after cutaneous exposure to radiation and that the collapse of skin
      antioxidant status interferes directly with wound healing in skin after radiation
      exposure. Thus a better understanding of the molecular events through which
      oxidative stress modulates the healing response could result in a more rational
      therapeutic approach to the pathological process induced after exposure of skin
      to radiation.

PMID- 17214514
TI  - TP53 and TP53-related genes associated with protection from apoptosis in the
      radioadaptive response.
AB  - We investigated the effect of administering priming low-dose radiation prior to
      high-dose radiation on the level of apoptosis and on the expression of TP53 and
      TP53-related genes in mouse splenocytes. The percentage of apoptotic cells was
      significantly lower in TP53(+/+) mice receiving priming radiation 2 to 168 h
      before the high-dose irradiation, compared to TP53(+/+) mice exposed to 2 Gy
      alone. In contrast, TP53(+/-) mice exhibited a reduced level of apoptosis only
      when priming was performed for 2 or 4 h prior to the high-dose irradiation. In
      TP53(+/+) mice, primed mice had higher TP53 expression than mice exposed to 2 Gy.
      Phospho-TP53 (ser15/18) expression was the highest in mice exposed to 2 Gy and
      intermediate in primed mice. Expression of p21 (CDKN1A) was higher in primed mice
      compared with mice exposed to 2 Gy. MDM2 expression remained at a high level in
      all mice receiving 2 Gy. Elevated phospho-ATM expression was observed only in
      mice exposed to 2 Gy. We conclude that TP53 plays a critical role in the
      radioadaptive response and that TP53 and TP53-related genes might protect cells
      from apoptosis through activation of the intracellular repair system.

PMID- 17214515
TI  - Evaluating the biological effects of intermittent 1.9 GHz pulse-modulated
      radiofrequency fields in a series of human-derived cell lines.
AB  - Several recent studies have suggested that radiofrequency (RF) fields may cause
      changes in a variety of cellular functions that may eventually lead to potential
      long-term health effects. In the present study, we have assessed the ability of
      non-thermal RF-field exposure to affect a variety of biological processes
      (including apoptosis, cell cycle progression, viability and cytokine production)
      in a series of human-derived cell lines (TK6, HL60 and Mono-Mac-6). Exponentially
      growing cells were exposed to intermittent (5 min on, 10 min off) 1.9 GHz pulse
      modulated RF fields for 6 h at mean specific absorption rates (SARs) of 0, 1 and
      10 W/kg. Concurrent negative (incubator) and positive (heat shock for 1 h at 43
      degrees C) controls were included in each experiment. Immediately after the 6-h
      exposure period and 18 h after exposure, cell pellets were collected and analyzed
      for cell viability, the incidence of apoptosis, and alterations in cell cycle
      kinetics. The cell culture supernatants were assessed for the presence of a
      series of human inflammatory cytokines (TNFA, IL1B, IL6, IL8, IL10, IL12) using a
      cytometric bead array assay. No detectable changes in cell viability, cell cycle
      kinetics, incidence of apoptosis, or cytokine expression were observed in any of
      RF-field-exposed groups in any of the cell lines tested, relative to the sham
      controls. However, the positive (heat-shock) control samples displayed a
      significant decrease in cell viability, increase in apoptosis, and alteration in
      cell cycle kinetics (G(2)/M block). Overall, we found no evidence that non
      thermal RF-field exposure could elicit any detectable biological effect in three
      human-derived cell lines.

PMID- 17214516
TI  - Evidence that individual variations in TP53 and CDKN1A protein responsiveness are
      related to inherent radiation sensitivity.
AB  - We tested the hypothesis that individual variations in the induction of the TP53
      tumor suppressor protein by radiation are related to inherent radiosensitivity.
      Thirty-two fibroblast cell strains were examined. Radiosensitivity was measured
      by a clonogenic survival assay. The induction of TP53 and its transcriptionally
      activated CDKN1A (p21) protein were studied by Western blotting 3 h after a
      single dose of 5 Gy. The relative cell culture age, as determined by the colony
      size distribution, was studied as a confounding factor. Survival curves showed
      wide range of radiosensitivity. The surviving fraction at 2 Gy (SF2) ranged
      between 0.02 and 0.49 (mean = 0.29, SD = 0.13). TP53 induction ranged between
      1.28 and 2.34 (mean = 1.80, SD = 0.31). CDKN1A showed a wider induction (1.09
      4.05, mean = 2.33, SD = 0.78). Positive correlations were observed between SF2
      and TP53 induction (R(2) = 0.62, P < 0.001) and CDKN1A (R(2) = 0.64, P < 0.001).
      No correlation with the colony size distribution was observed. In conclusion,
      these results suggest that the individual variations in radiosensitivity and in
      the level of induction of TP53 (and consequently CDKN1A) are congruent,
      irrespective of the genetic background of these nontransformed fibroblasts. It is
      postulated that underlying mechanisms culminating in a stronger TP53 induction
      lead to higher survival, presumably due to more efficient repair of radiation
      induced damage.

PMID- 17214517
TI  - The lethality of Ku86 (XRCC5) loss-of-function mutations in human cells is
      independent of p53 (TP53).
AB  - Ku86 is one of the two regulatory subunits of the DNA-PK (DNA-dependent protein
      kinase) complex that is required for DNA double-strand break repair in mammalian
      cells. In a previous study, by means of somatic gene targeting, we generated
      human cell lines deficient in Ku86 (XRCC5). Heterozygous human Ku86 cells
      exhibited a wide array of haploinsufficient phenotypes, including sensitivity to
      ionizing radiation, defects in DNA-PK and DNA end-binding activities, elevated
      levels of p53 (TP53) and gamma-H2AX foci, and a defect in cell proliferation with
      an increase in the frequency of aneuploid cells. Here we demonstrate that the
      overexpression of a human Ku86 cDNA complemented the deficiencies of these cells
      to wild-type levels. In contrast, Ku86 overexpression only partially rescued the
      telomere defects characteristic of Ku86 heterozygous cells and did not rescue
      their genetic instability. Additionally, in stark contrast to every other species
      described to date, we had shown earlier that homozygous human Ku86(-/-) cells are
      inviable, because they undergo 8 to 10 rounds of cell division before succumbing
      to apoptosis. The tumor suppressor protein p53 regulates the DNA damage response
      in mammalian cells and triggers apoptosis in the face of excessive DNA damage.
      Correspondingly, ablation of p53 expression has repeatedly been shown to
      significantly ameliorate the pathological effects of loss-of-function mutations
      for a large number of DNA repair genes. Surprisingly, however, even in a p53-null
      genetic background, the absence of Ku86 proved lethal. Thus the gene encoding
      Ku86 (XRCC5) is an essential gene in human somatic cells, and its absence cannot
      be suppressed by the loss of p53 function. These results suggest that Ku86
      performs an essential role in telomere maintenance in human cells.

PMID- 17214518
TI  - Initial yields of DNA double-strand breaks and DNA Fragmentation patterns depend
      on linear energy transfer in tobacco BY-2 protoplasts irradiated with helium,
      carbon and neon ions.
AB  - The ability of ion beams to kill or mutate plant cells is known to depend on the
      linear energy transfer (LET) of the ions, although the mechanism of damage is
      poorly understood. In this study, DNA double-strand breaks (DSBs) were quantified
      by a DNA fragment-size analysis in tobacco protoplasts irradiated with high-LET
      ions. Tobacco BY-2 protoplasts, as a model of single plant cells, were irradiated
      with helium, carbon and neon ions having different LETs and with gamma rays.
      After irradiation, DNA fragments were separated into sizes between 1600 and 6.6
      kbp by pulsed-field gel electrophoresis. Information on DNA fragmentation was
      obtained by staining the gels with SYBR Green I. Initial DSB yields were found to
      depend on LET, and the highest relative biological effectiveness (about 1.6) was
      obtained at 124 and 241 keV/microm carbon ions. High-LET carbon and neon ions
      induced short DNA fragments more efficiently than gamma rays. These results
      partially explain the large biological effects caused by high-LET ions in plants.

PMID- 17214519
TI  - Homology-directed repair is required for the development of radioresistance
      during S phase: interplay between double-strand break repair and checkpoint
      response.
AB  - The S-phase-dependent radioresistance to killing uniformly seen in eukaryotic
      cells is absent in radiosensitive mutants with defects in genes involved in the
      repair of DNA double-strand breaks (DSBs) by homologous recombination (homologous
      recombination repair: HRR). This implicates, for the first time, a concrete DNA
      repair process in the radiosensitivity of a specific cell cycle phase. The cell
      cycle-dependent fluctuations in radiosensitivity reflect a fundamental and well
      documented radiobiological phenomenon that still awaits a detailed molecular
      characterization. The underlying mechanisms are likely to combine aspects of DNA
      repair and cell cycle regulation. Advances in both fields allow a first
      dissection in the cell cycle of the molecular interplay between DSB repair and
      DNA damage checkpoint response and its contribution to cell survival. Here we
      review the available literature on the topic, speculate on the ramifications of
      this information for our understanding of cellular responses to DNA damage, and
      discuss future directions in research. An effort is made to integrate relevant
      phenomena of radiation action, such as low-dose radiosensitivity and the G(2)
      assay in this scheme.

PMID- 17214520
TI  - Mobile phone radiation and gene expression.

PMID- 17214523
TI  - Use of magnetic resonance imaging to measure facial soft tissue depth.
AB  - OBJECTIVE: To investigate the feasibility of using magnetic resonance imaging to
      estimate facial tissue depth at standard anthropological facial landmarks.
      DESIGN: Standard facial landmarks were marked with magnetic resonance imaging
      opaque markers on 10 normal subjects. Three observers estimated facial tissue
      depth at these landmarks on up to three separate occasions, and comparisons were
      made among the observers. SETTING: The study was conducted with volunteers at the
      University of Alberta Biomechanical Engineering unit. PARTICIPANTS: The
      volunteers were healthy individuals of both sexes between the ages of 18 and 30
      years. MAIN OUTCOME MEASURES: The technical error of measurement among observers
      was used as the main indicator of precision of measurement. RESULTS: Measurements
      of tissue depth showed tolerable technical error of measurement and were
      precisely measured within and among observers. CONCLUSIONS: Magnetic resonance
      images can be used to estimate tissue depth in human faces with precision.

PMID- 17214524
TI  - Speech outcome and velopharyngeal function in cleft palate: comparison of Le Fort
      I maxillary osteotomy and distraction osteogenesis--early results.
AB  - OBJECTIVE: To compare speech outcome and velopharyngeal (VP) status of subjects
      with repaired cleft palate who underwent either conventional Le Fort I osteotomy
      or maxillary distraction osteogenesis to correct maxillary hypoplasia. DESIGN:
      Prospective randomized study with blind assessment of speech outcome and VP
      status. SUBJECTS: Twenty-two subjects were randomized into conventional Le Fort I
      osteotomy and Le Fort I distraction groups. All were native Chinese (Cantonese)
      speakers. METHOD: Perceptual judgment of resonance and nasal emission, study of
      VP structures by nasoendoscopy, and instrumental measurement by nasometry.
      Assessments were performed preoperatively and at 3 months postoperatively. MAIN
      OUTCOME MEASURES: Assessment of VP closure, perceptual rating of hypernasality
      and nasal emission, nasalance, and amount of maxillary advancement. RESULTS:
      There was no statistical difference in any of the outcome measures between the 10
      subjects with conventional Le Fort I osteotomy and the 12 subjects with maxillary
      distraction: hypernasality (chi-square = 3.850, p = 0.221), nasal emission (chi
      square = 0.687, p = 0.774), VP gap size (chi-square = 1.527, p = 0.635, and
      nasalance (t = -0.145, p = 0.886). There was no correlation between amount of
      maxillary advancement and any of the outcome measures (p = .05 for all). Changes
      in VP gap size and resonance are described. CONCLUSION: Results need to be
      interpreted with caution because of the small sample size and early follow-up.
      However, this study utilized an assessment protocol involving a variety of
      outcome measures and careful consideration of reliability factors, which can be a
      model for further and follow-up studies.

PMID- 17214525
TI  - Psychological profile of Chinese with cleft lip and palate deformities.
AB  - OBJECTIVE: To assess the psychological well-being of patients with cleft lip and
      palate (CLP). PATIENTS/SETTING: Ninety-four Chinese CLP subjects between 10 and
      40 years of age were recruited from the Discipline of Oral and Maxillofacial
      Surgery, The University of Hong Kong, between June and December 2003. They were
      divided into two groups for comparison: adolescents (10-16 years old) and adults
      (17- 40 years old). A control group of 116 healthy non-CLP patients was also
      recruited during the same period. INTERVENTIONS: All CLP and non-CLP patients
      were asked to complete a set of four questionnaires to assess their psychological
      status. The questionnaires included the Social Avoidance and Distress Scale, the
      Satisfaction with Life Scale, the Culture-Free Self-Esteem Inventory, and the
      Chinese Miller Behavioral Style Scale. RESULTS: Chinese CLP patients exhibited
      levels of subjective well-being and social anxiety that were similar to the
      published levels of a group of British CLP patients. They also had significantly
      lower general and social self-esteem but higher parental self-esteem than the non
      CLP control group. CONCLUSION: CLP patients were generally satisfied with life
      and did not exhibit more social anxiety than the non-CLP control group. They also
      had a good relationship with their parents. Gender and educational level had no
      influence on their psychological profile. However, these CLP patients had lower
      self-esteem than non-CLP patients.

PMID- 17214526
TI  - Cleft palate and keratoconus in a child affected by fetal alcohol syndrome: an
      accidental association?
AB  - This report describes the case of a 9-year-old girl affected by fetal alcohol
      syndrome who presented at birth with blepharophimosis and a cleft palate, which
      was submitted to surgery. She was referred to our hospital for a visual acuity
      reduction, where a diagnosis of keratoconus was made. This case highlights the
      rarity of the association between fetal alcohol syndrome and cleft palate and the
      previously unreported association involving fetal alcohol syndrome-keratoconus
      and cleft palate-keratoconus.

PMID- 17214527
TI  - Bilateral macrostomia as an isolated pathology.
AB  - OBJECTIVE: Congenital macrostomia is a lateral orofacial cleft between the
      maxillary and mandibular components of the first branchial arch. Bilateral
      macrostomia is a poorly characterized malformation, with only 14 cases reported
      in the literature. The purpose of this study was to compare our experience with
      the world literature. METHOD: A retrospective analysis of 20 cases of bilateral
      congenital macrostomia was conducted; 6 cases were drawn from 2 maxillofacial
      surgery units and 14 cases from the world literature. Cases of bilateral
      congenital macrostomia were compared with cases of unilateral forms using a
      review of the literature post-1954. Among the six cases identified from the two
      maxillofacial surgery units, three were treated with linear sutures and three
      with Z-plasty. Subsequent aesthetic and functional results were analyzed.
      RESULTS: Compared to unilateral forms, bilateral macrostomia is more often
      isolated without ear or skin deformities. Moreover, there are a greater
      proportion of larger defects among cases with bilateral macrostomia when compared
      to unilateral macrostomia. Alimentation, phonation, and mouth opening were always
      normal. The two sides were always symmetric. Only one case presented with the
      complication of skin contractions during lip movement. CONCLUSION: The
      etiopathogenesis of bilateral macrostomia is unclear. Although over 50% of the
      reported cases of bilateral macrostomia are isolated, this condition presents a
      therapeutic challenge. In the case of bilateral forms, the surgeon must define
      the commissure position without a normal side. Repair thus requires extraoral
      landmarks and normal measurements.

PMID- 17214528
TI  - Predisposing factors to dental caries in children with cleft lip and palate: a
      review and strategies for early prevention.
AB  - OBJECTIVE: To review predisposing factors contributing to dental caries in
      patients with cleft lip, cleft palate, or both (CL/P). DESIGN: Patients with CL/P
      have a higher susceptibility to caries compared with the population group without
      clefts. A review of the literature was undertaken to determine factors that could
      account for the compromised oral hygiene and the high caries prevalence in
      patients with CL/P. RESULTS: After a literature review, modern strategies for the
      prevention of early childhood caries were developed and should be considered for
      integration into the overall management protocol of patients with CL/P.
      CONCLUSIONS: Preventive dental care is ever more so important in patients with
      CL/P compared with patients without clefts.

PMID- 17214529
TI  - Tongue-palate contact during bilabials in normal speech.
AB  - OBJECTIVE: Previous research using electropalatography (EPG) identified a
      compensatory articulation called bilabial-lingual double articulations. These
      double articulations were produced for bilabials by some speakers with cleft
      palate and involved closure at the lips occurring simultaneously with complete
      tongue-palate constriction. However, no normative English EPG data exist to
      confirm the abnormal status of these double articulations. DESIGN: This study
      reports normative data for EPG contact during bilabial closure. Acoustic and EPG
      data were recorded for bilabials in different vowel contexts. PARTICIPANTS: Eight
      normal English-speaking adults. MEASURES: One measure identified complete tongue
      palate constriction, and a second measure calculated percent contact. RESULTS:
      There were no instances of complete tongue-palate constriction, though some EPG
      contact occurred in the lateral regions of the palate. The vowel context
      significantly affected the amount of contact present, with /i/ having the most
      and /a/ having the least amount of contact. CONCLUSION: Complete tongue-palate
      constriction during bilabials of the type found in bilabial-lingual double
      articulations is not a feature of normal English speech and can therefore be
      considered an abnormal articulation pattern. Speech-language pathologists who use
      EPG in their clinical work should be aware that some lateral contact during
      bilabial closure is normal.

PMID- 17214530
TI  - Periodontal status and oral hygiene in two populations of cleft patients.
AB  - OBJECTIVE: To evaluate and compare the oral hygiene and periodontal status in
      children with unilateral and bilateral cleft lip and palate treated in Lodz,
      Poland, and Erlangen, Germany. DESIGN: Oral health was assessed by the presence
      of dental plaque, pocket depth, clinical attachment levels, and pathologic teeth
      mobility. SUBJECTS AND METHODS: Thirty-seven Polish and 63 German patients
      participated in this study. RESULTS: Poor oral hygiene was found in 57% of all
      subjects. In Erlangen, 60% of patients had optimal oral hygiene, compared to 19%
      in Lodz. The highest scores for dental plaque were noted in both groups in the
      cleft region. Healthy periodontium was significantly more frequent among German
      patients, whereas gingival bleeding was significantly more frequent among Polish
      patients. Pocket depths greater than 6 mm occurred only in German subjects. No
      statistically significant difference was observed between the amount of tooth
      areas with gingival recessions and the country of origin. Periodontal pockets
      deeper than 3.5 mm occurred more frequently during active orthodontic treatment.
      CONCLUSIONS: The oral hygiene regimens in Germany and Poland were not comparable,
      as more plaque was found in the Polish than in the German population. Plaque
      accumulation seems not to be a key factor in causing periodontal destruction in
      the cleft area. Factors other than oral hygiene should be considered of major
      importance in relation to the development of gingival recession on teeth in cleft
      areas.

PMID- 17214531
TI  - Congenital midline cervical cleft.
AB  - Congenital midline cervical cleft (CMCC) is a rare disorder of the ventral neck
      that is clinically evident at birth and must be differentiated from the more
      common thyroglossal duct cyst. The case of CMCC presented here was associated
      with chromosomes 13/14 de novo Robertsonian translocations as well as midline
      deformities including a sacral tuft and a minor tongue-tie. The case is presented
      as well as discussion of histopathology, embryology, and surgical treatment.

PMID- 17214532
TI  - Zygomaticotemporal synostosis: a rare cause of progressive facial asymmetry.
AB  - Cranial synostosis is relatively common; however, premature closure of a facial
      suture is remarkably rare. We describe an adolescent male with zygomaticotemporal
      synostosis that manifested as progressive midfacial and orbital asymmetry,
      angulation of the cranial base, and nasal deviation. To our knowledge, this is
      the first description of this anomaly in the literature.

PMID- 17214533
TI  - Tessier 3 cleft with clinical anophthalmia: two case reports and a review of the
      literature.
AB  - Tessier 3 cleft with clinical anophthalmia is one of the rarest craniofacial
      clefts, and hence little has been published about its management and treatment.
      This article presents two cases of Tessier 3 cleft with clinical anophthalmia. A
      review of the literature helps to diagnose these complex facial deformities. The
      treatment and etiopathogenesis are discussed.

PMID- 17214534
TI  - One- or two-stage palate closure in patients with unilateral cleft lip and
      palate: comparing cephalometric and occlusal outcomes.
AB  - OBJECTIVE: To assess facial growth and dentoalveolar development in two groups of
      patients with complete unilateral cleft lip and palate. Primary surgical
      treatment differed in the timing of hard palate closure. DESIGN: Forty-three
      patients with unilateral cleft lip and palate were examined. Twenty-two patients
      underwent early one-stage closure of the hard and soft palate cleft (mean age
      23.0 +/- 4.7 months); in 21 patients, the hard palate closure was delayed to 86.3
      +/- 39.2 months of age. Lateral cephalograms and dental casts were consecutively
      analyzed at four stages between 6 and 18 years of age. RESULTS: Lateral
      cephalometric analysis revealed no significant intergroup differences in the
      sagittal and vertical craniofacial dimensions at any time. Dental cast analysis
      showed constriction of the upper anterior arch width at the ages of 6 and 10
      years in patients with one-stage surgical palate closure, but a difference could
      no longer be verified at the ages of 15 and 18 years. CONCLUSIONS: The transverse
      distances in the upper jaw developed initially more positively in the group with
      delayed hard palate closure, but it became apparent later that the transverse
      deficiency after one-stage palate closure could be compensated for. When
      considering surgical treatment in general, the advantages of the delayed hard
      palate closure must be weighed against criteria favoring the early one-stage
      closure of the hard and soft palate.

PMID- 17214535
TI  - Failed attendances at hospital dental clinics among young patients with cleft lip
      and palate.
AB  - OBJECTIVE: To determine the frequency of missed dental appointments among
      children with a cleft lip and/or palate (CL/P). DESIGN: A prospective study of
      failed appointments over a 12-month period. SETTING: Three different CL/P clinics
      within a British dental hospital. PATIENTS: Forty-five CL/P children (mean age of
      8.8 years) and 45 age-matched, gender-matched, and postal code-matched noncleft
      patients. MAIN OUTCOME MEASURES: The overall percentage of missed appointments at
      three different clinics by CL/P patients and the difference in attendance rates
      at the pediatric dentistry clinic between CL/P and non-CL/P children. RESULTS:
      Pediatric dentistry had the highest rate of missed appointments (22.4%), followed
      by the multidisciplinary cleft clinic (9.2%) and the orthodontic clinic (8.8%).
      CL/P patients missed a significantly greater proportion of their pediatric
      dentistry appointments than noncleft children (22.4% versus 11.9%). Patients with
      a bilateral CL/P were significantly more likely to miss an appointment than
      patients with a unilateral CL/P. Age, gender, medical history, and distance
      traveled had no significant effect on attendance rates. CONCLUSIONS: Further work
      is needed to identify risk factors for poor attendance and to develop strategies
      to reduce the frequency of missed appointments in this vulnerable group.

PMID- 17214536
TI  - A cross-sectional study of speech in 10-year-old children with cleft palate:
      results and issues of rater reliability.
AB  - OBJECTIVES: To describe speech based on perceptual evaluation in a group of 10
      year-old children with cleft palate. A secondary aim was to investigate the
      reliability of speech-language pathologists' perceptual assessment of cleft
      palate speech. DESIGN: Retrospective cross-sectional study in children with cleft
      palate. External raters made assessments from randomized speech recordings.
      SUBJECTS: Thirty-eight children with unilateral cleft lip and palate (UCLP) or
      cleft palate only (CPO) and 10 children in a comparison group. MAIN OUTCOME
      MEASURES: Ratings of hypernasality, hyponasality, audible nasal air leakage, weak
      pressure consonants, and articulation. Exact agreement and weighted kappa values
      were used for reliability. RESULTS: Hypernasality was found in 25% of children
      with a cleft of the soft palate (CSP), 33% of children with a cleft of the hard
      and soft palate (CHSP), and 67% of children with a UCLP. Similar results were
      found for audible nasal air leakage. Articulation errors were found in 6% of the
      CHSP group and 25% of the UCLP group, whereas no child in the CSP group had
      articulation errors. The reliability was moderate to good for different
      variables, with lowest values for hypernasality. CONCLUSIONS: Speech results in
      this series seem less satisfactory than those reported in other published
      international studies, but it is difficult to draw any certain conclusions about
      speech results because of large methodological differences. Further developments
      to ensure high reliability of perceptual ratings of speech are called for.

PMID- 17214537
TI  - Craniofacial, craniocervical, and pharyngeal morphology in bilateral cleft lip
      and palate and obstructive sleep apnea patients.
AB  - OBJECTIVE: The aim of this study was to analyze craniofacial, craniocervical, and
      pharyngeal morphology in surgically treated bilateral cleft lip and palate (BCLP)
      men, untreated men with obstructive sleep apnea (OSA), and a reference group of
      men. SUBJECTS AND METHODS: Lateral cephalograms were obtained of 27 male BCLP
      patients (mean age 29.0 +/- 8.3 years), 27 untreated male OSA patients (mean age
      38.6 +/- 5.3 years), and 27 male controls serving as a reference group (mean age
      30.8 +/- 9.2 years). Tracings were made, and 26 variables representing
      craniofacial, craniocervical, and pharyngeal dimensions were obtained using
      Viewbox 3.1.1.6. software. The groups were compared using a one-way analysis of
      variance. RESULTS: Craniofacial, craniocervical, and pharyngeal morphology of
      BCLP and OSA patients was similar except for a significantly more retrusive
      maxilla in the BCLP group. Compared to the reference group, the BCLP and OSA
      groups had significantly larger craniocervical angulations, smaller depth of the
      oropharynx at the tip of the velum, and a more inferiorly positioned hyoid bone.
      Significantly larger vertical dimensions were found in the BCLP group compared to
      the reference group. CONCLUSIONS: Craniofacial, craniocervical, and pharyngeal
      morphology of BCLP and OSA patients demonstrate substantial similarities except
      for a significantly more retrusive maxilla in the BCLP group. It is suggested
      that airway obstruction and postural adaptation to the obstruction may possibly
      be related to the aberrant craniofacial, craniocervical, and pharyngeal
      morphology in OSA and in BCLP patients.

PMID- 17214538
TI  - Clinical correlation of chromosome 22q11.2 fluorescent in situ hybridization
      analysis and velocardiofacial syndrome.
AB  - OBJECTIVE: To identify characteristics associated with microdeletions of
      chromosome 22q11.2 ascertained by fluorescent in situ hybridization (FISH)
      analysis in patients with velopharyngeal insufficiency (VPI), cleft palate, or
      other clinical features of velocardiofacial syndrome (VCFS). DESIGN/SETTING:
      Retrospective review of all patients entered at one tertiary-level
      multidisciplinary cleft lip and palate and craniofacial anomalies panel from
      January 2000 to December 2003. PATIENTS: The study consisted of 115 patients. The
      presence or absence of the following clinical features was documented: cleft
      palate (submucous and overt), VPI, cardiac anomalies, renal anomalies, small
      stature, characteristic facies, developmental delay, psychiatric dysfunction, and
      family history. MAIN OUTCOME MEASURE: Correlation between presence or absence of
      clinical features of VCFS and presence or absence of 22q11.2 microdeletion by
      FISH analysis. RESULTS: Of the 16 patients (13.9%) who demonstrated 22q11.2
      microdeletion by FISH analysis, 16 had VPI (100%), 16 had small stature (100%),
      14 had cleft palate (88%), and 13 had characteristic facies (81%). Developmental
      delay was also present in 13 of these patients (81%), and seven had cardiac
      anomalies (44%). Multiple regression analysis revealed that the presence of
      characteristic facies and small stature statistically correlated with
      microdeletions of chromosome 22q11.2 by FISH studies (p < .05). CONCLUSIONS:
      Patients with microdeletions of chromosome 22q11.2 as demonstrated by FISH
      analysis were more likely to have VPI, small stature, cleft palate,
      characteristic facies, and developmental delay, in descending order. Statistical
      analysis showed that only characteristic facies and small stature correlated with
      22q11.2 microdeletions.

PMID- 17214539
TI  - Closure of a large palatal fistula with maxillary segmental distraction
      osteogenesis in a cleft palate patient.
AB  - Various techniques have been proposed for the repair of palatal clefts. The first
      surgical closure technique that should be kept in mind is the use of adjacent
      mucosal flaps. When the palatal cleft is too large to close with adjacent mucosal
      flaps, distant flaps such as from the tongue or nasolabial region may be
      considered. This report presents a cleft patient who had previously undergone an
      unsuccessful palatal cleft repair with a tongue flap. The size of the large
      palatal fistula was reduced by approximating the segments to each other with
      maxillary anterior segmental distraction osteogenesis to make it more manageable
      using conventional mucosal flaps.

PMID- 17214540
TI  - Predictors of referral to the North Carolina Child Service Coordination Program
      among infants with orofacial clefts.
AB  - OBJECTIVE: North Carolina has several programs that identify high-risk women and
      children for needed services, including the Child Service Coordination Program
      (CSCP). This study determines CSCP referral rates among infants with orofacial
      clefts (OFCs) and predictors of CSCP referral. We hypothesized receiving Medicaid
      and maternity care coordination (MCC) services increases the likelihood of CSCP
      referral. DESIGN AND SETTING: For births between 1999 and 2002, data were matched
      from North Carolina Vital Statistics, Health Services Information System (MCC and
      CSCP data), and North Carolina Birth Defects Monitoring Program. Multivariate
      analysis was used to determine crude and adjusted odds ratios for
      sociodemographic variables to predict CSCP referral. PARTICIPANTS: A total of 644
      mothers of live-born infants with OFCs in North Carolina were identified.
      RESULTS: About 45% of infants with OFCs were referred to the CSCP. Infants of
      mothers who were at least 30 years of age and mothers who had more than a high
      school education were significantly less likely to be referred to the CSCP.
      Compared with infants with OFCs whose mothers did not receive Medicaid, mothers
      who received Medicaid were 1.9 times more likely to be referred to the CSCP, and
      mothers who received Medicaid and MCC services were 2.3 times more likely.
      CONCLUSIONS: Receipt of Medicaid and MCC services and receipt of Medicaid alone
      were positively associated with CSCP referral. Future studies should examine the
      effects of the duration of MCC services and factors related to the timeliness of
      CSCP referral.

PMID- 17214541
TI  - Presurgical nasoalveolar molding therapy for the treatment of unilateral cleft
      lip and palate: a preliminary study.
AB  - OBJECTIVE: To evaluate the outcome of presurgical nasoalveolar molding (PNAM)
      therapy in the treatment of patients with nonsyndromic unilateral cleft and
      palate (UCLP). DESIGN: A prospective study with blinded measurements. PATIENTS:
      Twelve patients with UCLP treated from 1997 to 2003. INTERVENTIONS: The starting
      age for PNAM therapy was 26 days and the average length of the therapy was 110
      days. MAIN OUTCOME MEASURES: Measurements of intraoral and extraoral casts were
      made, and statistical analyses were used to compare the differences between pre-
      and posttherapy measurements. RESULTS: After PNAM therapy, there was a
      statistically significant decrease in both intersegment alveolar cleft distance
      and columellar deviation (p < .05). There was also a statistically significant
      increase in cleft nostril height, maxillary width, and columellar width (p <
      .05). Moreover, although there was no statistically significant reduction of the
      affected nostril width, it demonstrated on average 1.7-mm reduction after PNAM
      therapy. The length of the time the patient utilized the appliance and
      postmolding nostril height were found to have a statistically significant
      positive correlation (p < .05). CONCLUSIONS: PNAM therapy decreases intersegment
      alveolar cleft distance while permitting an increase in posterior maxillary arch
      width. It also increases nasal symmetry by decreasing columellar deviation,
      increasing nostril height on the affected side, maintaining bialar width of nose,
      increasing columellar width, and creating more symmetrical nostril heights and
      widths. The improvement of the height of the cleft nostril was correlated with
      the time the appliance was applied.

PMID- 17214544
TI  - Accumulation of viroid-specific small RNAs and increase in nucleolytic activities
      linked to viroid-caused pathogenesis.
AB  - Strong viroid-caused pathogenesis was achieved in tomato cv. Rutgers by biolistic
      transfer of severe or lethal potato spindle tuber viroid (PSTVd) strains, while
      other tomato genotypes (e.g., Moneymaker) were tolerant. With reciprocal hybrids
      between sensitive and tolerant genotypes, we show that plant depression dominates
      over tolerance. Biolistic transfer of the most pathogenic PSTVd strain AS1 to
      Nicotiana benthamiana, which is considered to be a symptomless PSTVd host, led to
      a strong pathogenesis reaction and stunting, suggesting the presence of specific
      viroid pathogenesis-promoting target(s) in this plant species. Total levels of
      small siRNA-like PSTVd-specific RNAs were enhanced in strongly symptomatic tomato
      and N. benthamiana plants after biolistic infection with AS1 in comparison to the
      mild QFA strain. This indicates association of elevated levels of viroid-specific
      small RNA with production of strong symptoms. In symptom-bearing tomato leaves in
      comparison to controls, an RNase of approximately 18 kDa was induced and the
      activity of a nuclease of 34 kDa was elevated by a factor of seven in the
      vascular system. Sequence analysis of the nuclease cDNA designated TBN1 showed
      high homology with plant apoptotic endonucleases. The vascular-specific
      pathogenesis action is supported by light microscopic observations demonstrating
      a certain lack of xylem tissue and an arrest of the establishment of new vascular
      bundles in collapsed plants.

PMID- 17214545
TI  - Characterisation of Plasmodium falciparum RESA-like protein peptides that bind
      specifically to erythrocytes and inhibit invasion.
AB  - The Plasmodium falciparum ring-erythrocyte surface antigen (RESA)-like putative
      protein was identified and characterised. PCR and RT-PCR assays revealed that the
      gene encoding this protein was both present and being transcribed in P.
      falciparum strain FCB-2 16 h after erythrocyte invasion. Indirect
      immunofluorescence studies detected this protein in infected erythrocyte (IE)
      cytosol in dense fluorescent granules similar to Maurer's clefts at 16-20 h
      (parasites in ring and trophozoite stages) and very strongly on IE membranes at
      22 h, suggesting that it is synthesised during early ring stages (16 h) and
      transported to the infected red blood cell (RBC) membrane surface during the
      trophozoite stage (22 h). Western blotting showed that antisera produced against
      polymerised synthetic peptides of this protein recognised a 72-kDa band in P.
      falciparum schizont lysate. P. falciparum RESA-like peptides used in normal RBC
      binding assays revealed that peptides 30326 ((101)NAEKI LGFDD KNILE ALDLFY(120)),
      30334 ((281)RVTWK KLRTK MIKAL KKSLTY(300)) and 30342 ((431)SSPQR LKFTA GGGFC
      GKLRNY(450)) bind with high activity and saturability, presenting nM affinity
      constants. These peptides contain alpha-helical structural elements, as
      determined by circular dichroism, and inhibit P. falciparum in vitro invasion of
      normal RBCs by up to 91%, suggesting that some RESA-like protein regions are
      involved in intra-erythrocyte stage P. falciparum invasion.

PMID- 17214546
TI  - Structural modifications to a high-activity binding peptide located within the
      PfEMP1 NTS domain induce protection against P. falciparum malaria in Aotus
      monkeys.
AB  - Binding of P. falciparum-infected erythrocytes to vascular endothelium and to
      uninfected erythrocytes is mediated by the parasite-derived variant erythrocyte
      membrane protein PfEMP-1 and various receptors, both on the vascular endothelium
      and on the erythrocyte surface. Consecutive, non-overlapping peptides spanning
      the N-terminal segment (NTS) and Duffy-binding-like PfEMP1 sequence alpha-domain
      (DBLalpha) of this protein were tested in erythrocyte and C32 cell binding
      assays. Eight peptides specifically bound to C32 cells, and were named high
      activity binding peptides (HABPs). No erythrocyte binding HABPs were found in
      this region. Strikingly, three HABPs [6504 ((1)MVELA KMGPK EAAGG DDIED(20)), 6505
      ((21)ESAKH MFDRI GKDVY DKVKE(40)) and 6506 ((41)YRAKE RGKGL QGRLS EAKFEK(60))]
      are located within the NTS, for which no specific function has yet been
      described. HABP 6505 is neither immunogenic nor protection-inducing; therefore,
      based on our previous reports, critical amino acids (shown in bold) in HABP-C32
      cell binding were identified and replaced to modify HABP immunogenicity and
      protectivity. Analogue peptide 12722 (ESAKH KFDRI GKDVY DMVKE) produced high
      antibody titres and completely protected three out of 12 vaccinated Aotus monkeys
      and 23410 (KHKFD FIGKI VYDMV KER) also produced high protection-inducing titres
      and completely protected one out of eight monkeys. (1)H NMR studies showed that
      all peptides were helical. Binding of these peptides to isolated HLADRbeta1
      molecules did not reveal any preference, suggesting that they could bind to
      molecules not studied here.

PMID- 17214547
TI  - Characterisation of YtfM, a second member of the Omp85 family in Escherichia
      coli.
AB  - Omp85 proteins form a ubiquitous protein family, members of which are found in
      all Gram-negative bacteria. Omp85 of Neisseria meningitidis and YaeT of
      Escherichia coli are shown to be essential for outer membrane biogenesis.
      Interestingly, there exists a homologue to YaeT in E. coli and many
      proteobacteria, denoted YtfM, the function of which has not been described yet.
      Like YaeT, YtfM is predicted to consist of an amino-terminal periplasmic domain
      and a membrane-located carboxy-terminal domain. In this study, we present a first
      characterisation of YtfM by comparison to YaeT concerning structural, biochemical
      and electrophysiological properties. Furthermore, a knockout strain revealed that
      ytfM is a non-essential gene and lack of the protein had no effect on outer
      membrane composition and integrity. The only observable phenotype was strongly
      reduced growth, indicating an important role of YtfM in vivo.

PMID- 17214548
TI  - Presence of the propeptide on recombinant lysosomal dipeptidase controls both
      activation and dimerization.
AB  - Lysosomal dipeptidase catalyzes the hydrolysis of dipeptides with unsubstituted
      terminals. It is a homodimer and binds zinc. Dimerization is an important issue
      in understanding the enzyme's function. In this study, we investigated the
      influence of the propeptide on the folding and dimerization of recombinant
      lysosomal dipeptidase. For this purpose, we separately cloned and overexpressed
      the mature protein and the proenzyme. The overexpressed proteins were localized
      exclusively to insoluble inclusion bodies. Refolding of the urea-solubilized
      inclusion bodies showed that only dipeptidase lacking the propeptide was dimeric.
      The soluble renatured proenzyme was a monomer, although circular dichroism and
      fluorescence spectra of the proenzyme indicated the formation of secondary and
      tertiary structure. The propeptide thus controls dimerization, as well as
      activation, of lysosomal dipeptidase.

PMID- 17214549
TI  - Conformational studies on Arabidopsis sulfurtransferase AtStr1 with spectroscopic
      methods.
AB  - Sulfurtransferases/rhodaneses (Str) are enzymes widely distributed in archaea,
      prokaryota and eukaryota, and catalyze the transfer of sulfur from a donor
      molecule to a thiophilic acceptor substrate. In this reaction, Str cycles between
      the sulfur-free and the sulfur-substituted form. Two-domain Str consist of two
      globular domains of nearly identical size and conformation connected by a short
      linker sequence, which is elongated in plant two-domain Str proteins compared to
      Str in other organisms. The two-domain Arabidopsis thaliana Str1 protein
      (At1g79230) was expressed in Escherichia coli as a mature protein, as a variant
      without the elongated linker sequence, and as AtStr1C332S and AtStr1C339V. The
      persulfuration state of the purified recombinant proteins was investigated in the
      presence and absence of sulfur donors by fluorescence spectroscopy. The secondary
      structure was analyzed by circular dichroism (CD) in the far-UV range, while
      overall changes in tertiary structure were determined by CD in the near-UV range.
      Finally, protein stability was analyzed by tryptic digestion. The elongated
      linker sequence is essential for correct conformation and stability, and thereby
      affects the catalytic activity of AtStr1. Replacement of the catalytic cysteine
      residue C332 leads to higher rigidity of the molecule, whereas replacement of
      C339 does not lead to any conformational changes, providing evidence of the
      direct involvement of C339 in catalysis.

PMID- 17214550
TI  - Glycine-assisted enhancement of 1,4-beta-d-xylan xylanohydrolase activity at
      alkaline pH with a pH optimum shift.
AB  - This is the first report describing the enhancement of xylanase activity by the
      neutral amino acid glycine. Xylanase activity is increased seven-fold at alkaline
      pH in the presence of glycine and its pH optimum is shifted from pH 7 to 8
      without using any protein engineering techniques. Analysis of the steady-state
      kinetics revealed that glycine in the reaction mixture increases the K(m) and
      k(cat) values of the enzyme. Chemoaffinity labeling and studies using glycine
      esters indicate an involvement of the carboxylate ion of glycine in enhancing
      xylanase catalytic activity. A novel possible mechanism for the glycine-assisted
      catalytic action of xylanase is proposed.

PMID- 17214551
TI  - Asef is a Cdc42-specific guanine nucleotide exchange factor.
AB  - Asef is a member of the Dbl-family of guanine nucleotide exchange factors (GEFs)
      with a proposed specificity for the small GTPase Rac1. Here we investigated the
      specificity and regulation of Asef by measuring its GEF activity in vitro and
      observed hardly any activity towards Rac1, Rac2 and Rac3, or RhoA and TC10. In
      contrast, various purified Asef protein fragments catalyzed the nucleotide
      exchange reaction of Cdc42. The Cdc42GEF activity of the Dbl homology (DH) domain
      of Asef was significantly higher in the presence of the pleckstrin homology (PH)
      domain. Our data strongly suggest that Asef is a canonical Cdc42GEF, which
      employs its PH domain to efficiently stabilize its autoinhibited state, but also
      to facilitate nucleotide exchange activity of the DH domain after its activation
      by upstream signals.

PMID- 17214552
TI  - Metal-binding sites at the active site of restriction endonuclease BamHI can
      conform to a one-ion mechanism.
AB  - The number of metal ions required for phosphoryl transfer in restriction
      endonucleases is still an unresolved question in molecular biology. The two
      Ca(2+) and Mn(2+) ions observed in the pre- and post-reactive complexes of BamHI
      conform to the classical two-metal ion choreography. We probed the Mg(2+)
      cofactor positions at the active site of BamHI by molecular dynamics simulations
      with one and two metal ions present and identified several catalytically relevant
      sites. These can mark the pathway of a single ion during catalysis, suggesting
      its critical role, while a regulatory function is proposed for a possible second
      ion.

PMID- 17214553
TI  - Interaction of the cellular prion protein with raft-like lipid membranes.
AB  - Conversion of the cellular isoform of the prion protein (PrP(C)) into the disease
      associated isoform (PrP(Sc)) plays a key role in the development of prion
      diseases. Within its cellular pathway, PrP(C) undergoes several posttranslational
      modifications, i.e., the attachment of two N-linked glycans and a glycosyl
      phosphatidyl inositol (GPI) anchor, by which it is linked to the plasma membrane
      on the exterior cell surface. To study the interaction of PrP(C) with model
      membranes, we purified posttranslationally modified PrP(C) from transgenic
      Chinese hamster ovary (CHO) cells. The mono-, di- and oligomeric states of PrP(C)
      free in solution were analyzed by analytical ultracentrifugation. The interaction
      of PrP(C) with model membranes was studied using both lipid vesicles in solution
      and lipid bilayers bound to a chip surface. The equilibrium and mechanism of
      PrP(C) association with the model membranes were analyzed by surface plasmon
      resonance. Depending on the degree of saturation of binding sites, the
      concentration of PrP(C) released from the membrane into aqueous solution was
      estimated at between 10(-9) and 10(-7) M. This corresponds to a free energy of
      the insertion reaction of -48 kJ/mol. Consequences for the conversion of PrP(C)
      to PrP(Sc) are discussed.

PMID- 17214554
TI  - Tissue-specific transcription factor HNF4alpha inhibits cell proliferation and
      induces apoptosis in the pancreatic INS-1 beta-cell line.
AB  - Hepatocyte nuclear factor 4alpha (HNF4alpha) is a tissue-specific transcription
      factor expressed in many cell types, including pancreatic beta-cells. Mutations
      in the HNF4alpha gene in humans give rise to maturity-onset diabetes of the young
      (MODY1) characterized by defective insulin secretion by beta-cells. To elucidate
      the mechanism underlying this disease, we introduced the splice form HNF4alpha2
      or HNF4alpha8 into the rat beta-cell line INS-1. Upon tetracycline-induced
      expression, both HNF4alpha isoforms caused distinct changes in cell morphology
      and a massive loss of cell numbers that was correlated with reduced proliferation
      and induced apoptosis. This differential activity was reflected in
      oligonucleotide microarray analysis that identified more genes affected by
      HNF4alpha2 compared to HNF4alpha8, and suggests that both isoforms regulate
      largely the same set of genes, with HNF4alpha2 being a stronger transactivator.
      We verified the induction of selected transcripts by real-time RT-PCR, including
      KAI1 and AIF, both known to have apoptotic potential. By establishing cell lines
      with inducible expression of these target genes, we deduce that both factors are
      insufficient to induce apoptosis. We propose that the anti-proliferative and
      apoptotic properties of HNF4alpha may be an essential feature impaired in MODY1
      and possibly also in type 2 diabetes.

PMID- 17214555
TI  - Binding of aflatoxins to the 20S proteasome: effects on enzyme functionality and
      implications for oxidative stress and apoptosis.
AB  - Aflatoxins (AF) are contaminants of improperly stored foods; they are potent
      genotoxic and carcinogenic compounds, exerting their effects through damage to
      DNA. They can also induce mutations that increase oxidative damage. The goal of
      this study was to evaluate the possibility that a third mechanism could be
      involved in the carcinogenic action of aflatoxins, namely, direct binding to key
      enzymes involved in the regulatory pathways of the cell cycle, thereby modulating
      enzyme functionality. The 20S constitutive and immunoproteasome peptidase and
      proteolytic activities were assayed in the presence of aflatoxins B1, G1 and M1.
      All three toxins activated multiple peptidase activities of the proteasome.
      Aflatoxin (AF) M1 was the most potent activator of proteasome activity, while the
      constitutive 20S proteasome was specifically stimulated by AFG1. Furthermore, the
      effects of AFB1 on cultured hepatoma cells were investigated and the various
      proteasomal activities determined with cell lysates were differently affected.
      Taking into account the key role of the proteasome in cellular defense against
      oxidative stress, the carbonyl group content and the activities of antioxidant
      enzymes in cell lysates were analyzed. The proapoptotic effect of AFB1 was also
      investigated by measuring caspase-3 activity and cellular levels of p27 and
      IkappaBalpha.

PMID- 17214556
TI  - The insect metalloproteinase inhibitor gene of the lepidopteran Galleria
      mellonella encodes two distinct inhibitors.
AB  - The insect metalloproteinase inhibitor (IMPI) from the greater wax moth, Galleria
      mellonella, represents the first and to date only specific inhibitor of microbial
      metalloproteinases reported from animals. Here, we report on the characterization
      including carbohydrate analysis of two recombinant constructs encoded by impi
      cDNA either upstream or downstream of the furin cleavage site identified. rIMPI
      1, corresponding to native IMPI purified from hemolymph, is encoded by the N
      terminal part of the impi sequence, whereas rIMPI-2 is encoded by its C-terminal
      part. rIMPI-1 is glycosylated at N48 with GlcNAc2Man3, showing fucosylation to
      different extents. Similarly, rIMPI-2 is glycosylated at N149 with GlcNAc2Man3,
      but is fully fucosylated. rIMPI-1 represents a promising template for the design
      of second-generation antibiotics owing to its specific activity against
      thermolysin-like metalloproteinases produced by human pathogenic bacteria such as
      Vibrio vulnificus. In contrast, rIMPI-2 does not inhibit bacterial
      metalloproteinases, but is moderately active against recombinant human matrix
      metalloproteinases (MMPs). Both microbial metalloproteinases and MMPs induce
      expression of the impi gene when injected into G. mellonella larvae. These
      findings provide evidence that the impi gene encodes two distinct inhibitors, one
      inhibiting microbial metalloproteinases and contributing to innate immunity, the
      other putatively mediating regulation of endogenous MMPs during metamorphosis.

PMID- 17214557
TI  - Activation profiles of the zymogen of aspergilloglutamic peptidase.
AB  - Aspergilloglutamic peptidase produced by Aspergillus niger var. macrosporus
      belongs to the novel glutamic peptidase family. Its zymogen is autocatalytically
      activated under acidic conditions to the mature enzyme with a two-chain
      structure. Analyses by SDS-PAGE and mass spectrometry of the activation products
      of the recombinant zymogen showed that the major pathway of activation includes
      initial fast cleavage at Glu12-Ala13, followed by stepwise cleavages in the N
      terminal and intervening propeptide regions. Essentially the same activation
      profile was obtained with the recombinant zymogen lacking the N-terminal 12-aa
      sequence. The missing region includes the most prominent cluster of basic
      residues of the propeptide, indicating low importance of this cluster for
      activation and refolding of the zymogen.

PMID- 17214558
TI  - Network modeling of adult neurogenesis: shifting rates of neuronal turnover
      optimally gears network learning according to novelty gradient.
AB  - Apoptotic and neurogenic events in the adult hippocampus are hypothesized to play
      a role in cognitive responses to new contexts. Corticosteroid-mediated stress
      responses and other neural processes invoked by substantially novel contextual
      changes may regulate these processes. Using elementary three-layer neural
      networks that learn by incremental synaptic plasticity, we explored whether the
      cognitive effects of differential regimens of neuronal turnover depend on the
      environmental context in terms of the degree of novelty in the new information to
      be learned. In "adult" networks that had achieved mature synaptic connectivity
      upon prior learning of the Roman alphabet, imposition of apoptosis/neurogenesis
      before learning increasingly novel information (alternate Roman < Russian <
      Hebrew) reveals optimality of informatic cost benefits when rates of turnover are
      geared in proportion to the degree of novelty. These findings predict that
      flexible control of rates of apoptosis-neurogenesis within plastic, mature neural
      systems optimizes learning attributes under varying degrees of contextual change,
      and that failures in this regulation may define a role for adult hippocampal
      neurogenesis in novelty- and stress-responsive psychiatric disorders.

PMID- 17214559
TI  - The role of the lateral prefrontal cortex and anterior cingulate in stimulus
      response association reversals.
AB  - Many complex tasks require us to flexibly switch between behavioral rules,
      associations, and strategies. The prefrontal cerebral cortex is thought to be
      critical to the performance of such behaviors, although the relative contribution
      of different components of this structure and associated subcortical regions are
      not fully understood. We used functional magnetic resonance imaging to measure
      brain activity during a simple task which required repeated reversals of a rule
      linking a colored cue and a left/right motor response. Each trial comprised three
      discrete events separated by variable delay periods. A colored cue instructed
      which response was to be executed, followed by a go signal which told the subject
      to execute the response and a feedback instruction which indicated whether to
      "hold" or "flip" the rule linking the colored cue and response. The design
      allowed us to determine which brain regions were recruited by the specific
      demands of preparing a rule contingent motor response, executing such a response,
      evaluating the significance of the feedback, and reconfiguring stimulus-response
      (SR) associations. The results indicate that an increase in neural activity
      occurs within the anterior cingulate gyrus under conditions in which SR
      associations are labile. In contrast, lateral frontal regions are activated by
      unlikely/unexpected perceptual events regardless of their significance for
      behavior. A network of subcortical structures, including the mediodorsal nucleus
      of the thalamus and striatum were the only regions showing activity that was
      exclusively correlated with the neurocognitive demands of reversing SR
      associations. We conclude that lateral frontal regions act to evaluate the
      behavioral significance of perceptual events, whereas medial frontal-thalamic
      circuits are involved in monitoring and reconfiguring SR associations when
      necessary.

PMID- 17214560
TI  - Brain response to unexpected novel noises in children with low and high trait
      anxiety.
AB  - The behavioral inhibition system [Gray, J. A. The neuropsychology of anxiety: An
      enquiry into the functions of the septo-hippocampal system. Oxford: Oxford
      University Press, 1982] proposes that anxiety is associated with the processing
      of novel stimuli. We aimed to explore this relationship by recording auditory
      event-related potentials associated with unexpected novel noises in typically
      developing children. Children aged 10-14 years with low (n = 12) and high (n =
      11) self-report trait anxiety were assessed using a novelty oddball task. The N1
      associated with novel stimuli, specifically the "N1c" component maximal at
      temporal lobe sites, was of significantly longer latency (p = .014) and greater
      amplitude (p = .004) in the high compared with the low anxious group. This group
      difference was supported by linear correlations between N1c amplitude and trait
      anxiety scores. There was no effect of anxiety on the later novelty P3. These
      data suggest a subtle moderating role of trait anxiety on brain response to
      novelty, and further research with clinically anxious children is indicated.

PMID- 17214561
TI  - Selective attention supports working memory maintenance by modulating perceptual
      processing of distractors.
AB  - Selective attention has been shown to bias sensory processing in favor of
      relevant stimuli and against irrelevant or distracting stimuli in perceptual
      tasks. Increasing evidence suggests that selective attention plays an important
      role during working memory maintenance, possibly by biasing sensory processing in
      favor of to-be-remembered items. In the current study, we investigated whether
      selective attention may also support working memory by biasing processing against
      irrelevant and potentially distracting information. Event-related potentials
      (ERPs) were recorded while subjects (n = 22) performed a delayed-recognition task
      for faces and shoes. The delay period was filled with face or shoe distractors.
      Behavioral performance was impaired when distractors were congruent with the
      working memory domain (e.g., face distractor during working memory for faces)
      relative to when distractors were incongruent with the working memory domain
      (e.g., face distractor during shoe working memory). If attentional biasing
      against distractor processing is indeed functionally relevant in supporting
      working memory maintenance, perceptual processing of distractors is predicted to
      be attenuated when distractors are more behaviorally intrusive relative to when
      they are nonintrusive. As such, we predicted that perceptual processing of
      distracting faces, as measured by the face-sensitive N170 ERP component, would be
      reduced in the context of congruent (face) working memory relative to incongruent
      (shoe) working memory. The N170 elicited by distracting faces demonstrated
      reduced amplitude during congruent versus incongruent working memory. These
      results suggest that perceptual processing of distracting faces may be attenuated
      due to attentional biasing against sensory processing of distractors that are
      most behaviorally intrusive during working memory maintenance.

PMID- 17214562
TI  - The neural substrate of human empathy: effects of perspective-taking and
      cognitive appraisal.
AB  - Whether observation of distress in others leads to empathic concern and
      altruistic motivation, or to personal distress and egoistic motivation, seems to
      depend upon the capacity for self-other differentiation and cognitive appraisal.
      In this experiment, behavioral measures and event-related functional magnetic
      resonance imaging were used to investigate the effects of perspective-taking and
      cognitive appraisal while participants observed the facial expression of pain
      resulting from medical treatment. Video clips showing the faces of patients were
      presented either with the instruction to imagine the feelings of the patient
      ("imagine other") or to imagine oneself to be in the patient's situation
      ("imagine self"). Cognitive appraisal was manipulated by providing information
      that the medical treatment had or had not been successful. Behavioral measures
      demonstrated that perspective-taking and treatment effectiveness instructions
      affected participants' affective responses to the observed pain. Hemodynamic
      changes were detected in the insular cortices, anterior medial cingulate cortex
      (aMCC), amygdala, and in visual areas including the fusiform gyrus. Graded
      responses related to the perspective-taking instructions were observed in middle
      insula, aMCC, medial and lateral premotor areas, and selectively in left and
      right parietal cortices. Treatment effectiveness resulted in signal changes in
      the perigenual anterior cingulate cortex, in the ventromedial orbito-frontal
      cortex, in the right lateral middle frontal gyrus, and in the cerebellum. These
      findings support the view that humans' responses to the pain of others can be
      modulated by cognitive and motivational processes, which influence whether
      observing a conspecific in need of help will result in empathic concern, an
      important instigator for helping behavior.

PMID- 17214563
TI  - Genetic variations of the NR3A subunit of the NMDA receptor modulate prefrontal
      cerebral activity in humans.
AB  - INTRODUCTION: Recently, a novel N-methyl-D-aspartate (NMDA) receptor subunit,
      NR3A, has been discovered in the brain. This subunit decreases NMDA receptor
      activity by modulating the calcium permeability of the receptor channel and
      current density in cortical cells. Because the NR3A is expressed in the human
      prefrontal cortex, we hypothesized that genetic variations of the NR3A subunit
      modulate prefrontal activation. METHODS: Electromagnetic activity during
      selective attention (auditory oddball task with target processing) was measured
      in 281 healthy subjects. Genotyping of a missense variation (rs10989591,
      Val362Met) of the NR3A gene was performed. RESULTS: Individuals carrying Val/Val
      genotype showed significantly reduced frontal P300 amplitudes compared with
      Met/Met subjects. Subsequent low-resolution electromagnetic source analysis
      revealed that this group difference is likely caused by reduced activation in the
      inferior frontal gyrus. CONCLUSIONS: It was shown for the first time that the
      genetic constitution of the subunit composition of NMDA receptor regulation might
      be relevant for prefrontal information processing in humans. The results
      underline the pivotal role of glutamate in frontal lobe function and indicate
      that the NR3A subunit could be a plausible candidate gene for diseases with
      prefrontal dysfunctions.

PMID- 17214564
TI  - Activation of right inferior frontal gyrus during response inhibition across
      response modalities.
AB  - The go/no-go task, which effectively taps the ability to inhibit prepotent
      response tendency, has consistently activated the lateral prefrontal cortex,
      particularly the right inferior frontal gyrus (rIFG). On the other hand, rIFG
      activation has rarely been reported in the antisaccade task, seemingly an
      oculomotor version of the manual go/no-go task. One possible explanation for the
      variable IFG activation is the modality difference of the two tasks: The go/no-go
      task is performed manually, whereas the antisaccade task is performed in the
      oculomotor modality. Another explanation is that these two tasks have different
      task structures that require different cognitive processes: The traditional
      antisaccade task requires (i) configuration of a preparatory set prior to
      antisaccade execution and (ii) response inhibition at the time of antisaccade
      execution, whereas the go/no-go task requires heightened response inhibition
      under a minimal preparatory set. To test these possibilities, the traditional
      antisaccade task was modified in the present functional magnetic resonance
      imaging study such that it required heightened response inhibition at the time of
      antisaccade execution under a minimal preparatory set. Prominent activation
      related to response inhibition was observed in multiple frontoparietal regions,
      including the rIFG. Moreover, meta-analyses revealed that the rIFG activation in
      the present study was observed in the go/no-go tasks but not in the traditional
      antisaccade task, indicating that the rIFG activation was sensitive to the task
      structure difference, but not to the response modality difference. These results
      suggest that the rIFG is part of a network active during response inhibition
      across different response modalities.

PMID- 17214565
TI  - Manipulating the experienced onset of intention after action execution.
AB  - Using transcranial magnetic stimulation (TMS), we have tested the time needed for
      the perceived onset of spontaneous motor intention to be fully determined. We
      found that TMS applied over the presupplementary motor area after the execution
      of a simple spontaneous action shifted the perceived onset of the motor intention
      backward in time, and shifted the perceived time of action execution forward in
      time. The size of the effect was similar regardless of whether TMS was applied
      immediately after the action or 200 msec after. The results of three control
      studies suggest that this effect is time-limited, specific to modality, and also
      specific to the anatomical site of stimulation. We conclude that the perceived
      onset of intention depends, at least in part, on neural activity that takes place
      after the execution of action. A model, which is based on the mechanism of cue
      integration under the presence of noise, is offered to explain the results. The
      implications for the conscious control of spontaneous actions are discussed.

PMID- 17214566
TI  - Illusory contours do not pass through the "blind spot".
AB  - Our visual percepts are not fully determined by the physical stimulus input. That
      is why we perceive crisp bounding contours even in the absence of luminance
      defined borders in visual illusions such as the Kanizsa figure. It is important
      to understand which neural processes are involved in creating these artificial
      visual experiences because this might tell us how we perceive coherent objects in
      natural scenes, which are characterized by mutual overlap. We have already shown
      using functional magnetic resonance imaging [Maertens, M., & Pollmann, S. fMRI
      reveals a common neural substrate of illusory and real contours in v1 after
      perceptual learning. Journal of Cognitive Neuroscience, 17, 1553-1564, 2005] that
      neurons in the primary visual cortex (V1) respond to these stimuli. Here we
      provide support for the hypothesis that V1 is obligatory for the discrimination
      of the curvature of illusory contours. We presented illusory contours across the
      portion of the visual field corresponding to the physiological "blind spot." Four
      observers were extensively trained and asked to discriminate fine curvature
      differences in these illusory contours. A distinct performance drop (increased
      errors and response latencies) was observed when illusory contours traversed the
      blind spot compared to when they were presented in the "normal" contralateral
      visual field at the same eccentricity. We attribute this specific performance
      deficit to the failure to build up a representation of the illusory contour in
      the absence of a cortical representation of the "blind spot" within V1. The
      current results substantiate the assumption that neural activity in area V1 is
      closely related to our phenomenal experience of illusory contours in particular,
      and to the construction of our subjective percepts in general.

PMID- 17214567
TI  - "Sequence Agnosia" in Balint's syndrome: defects in visuotemporal processing
      after bilateral parietal damage.
AB  - Balint's syndrome is characterized by visuospatial dysfunction, with failure to
      attend to multiple objects in space and poor spatial localization manifested as
      impaired reaching and saccadic targeting. Less investigated in this disorder is
      perceptual processing along the dimension of time. We studied the performance of
      a patient with Balint's syndrome on two oddity paradigms in which she had to
      indicate which of three objects was different in color, shape, or structure. Her
      initial difficulty with processing multiple objects present simultaneously in
      different locations recovered, but she had persistent difficulty processing
      objects seen sequentially at the same location. Further studies showed that this
      deficit was not due to impairments in sustained attention or in distributing
      attention over time, but to impaired processing of temporal sequences. The
      deficit was also present with auditory stimuli, indicating a multimodal failure
      of temporal sequencing. These findings show that bilateral parietal lesions
      affect not only the spatial but also the temporal organization of perception.

PMID- 17214568
TI  - Temporal order is coded temporally in the brain: early event-related potential
      latency shifts underlying prior entry in a cross-modal temporal order judgment
      task.
AB  - The speeding-up of neural processing associated with attended events (i.e., the
      prior-entry effect) has long been proposed as a viable mechanism by which
      attention can prioritize our perception and action. In the brain, this has been
      thought to be regulated through a sensory gating mechanism, increasing the
      amplitudes of early evoked potentials while leaving their latencies unaffected.
      However, the majority of previous research has emphasized speeded responding and
      has failed to emphasize fine temporal discrimination, thereby potentially lacking
      the sensitivity to reveal putative modulations in the timing of neural
      processing. In the present study, we used a cross-modal temporal order judgment
      task while shifting attention between the visual and tactile modalities to
      investigate the mechanisms underlying selective attention electrophysiologically.
      Our results indicate that attention can indeed speed up neural processes during
      visual perception, thereby providing the first electrophysiological support for
      the existence of prior entry.

PMID- 17214569
TI  - Expectancy induces dynamic modulation of corticospinal excitability.
AB  - Behavioral studies using motor preparation paradigms have revealed that increased
      expectancy of a response signal shortens reaction times (RTs). Neurophysiological
      data suggest that in such paradigms, not only RT but also neuronal activity in
      the motor structures involved is modulated by expectancy of behaviorally relevant
      events. Here, we directly tested whether expectancy of a response signal
      modulates excitability of the corticospinal system used in the subsequent
      movement. We combined single- and paired-pulse transcranial magnetic stimulation
      (TMS) over the primary motor cortex with a simple RT task with variable
      preparatory delays. We found that, in line with typical behavioral observations,
      the subjects' RTs decreased with increasing response signal expectancy. TMS
      results revealed a modulation of corticospinal excitability in correspondence
      with response signal expectancy. Besides an increased excitability over the time
      course of the preparatory delay, corticospinal excitability transiently increased
      whenever a response signal was expected. Paired-pulse TMS showed that this
      modulation is unlikely to be mediated by excitability changes in interneuronal
      inhibitory or facilitatory networks in the primary motor cortex. Changes in
      corticospinal synchronization or other mechanisms involving spinal circuits are
      candidates mediating the modulation of corticospinal excitability by expectancy.

PMID- 17214570
TI  - Too many trees to see the forest: performance, event-related potential, and
      functional magnetic resonance imaging manifestations of integrative congenital
      prosopagnosia.
AB  - Neuropsychological, event-related potential (ERP), and functional magnetic
      resonance imaging (fMRI) methods were combined to provide a comprehensive
      description of performance and neurobiological profiles for K.W., a case of
      congenital prosopagnosia. We demonstrate that K.W.'s visual perception is
      characterized by almost unprecedented inability to identify faces, a large bias
      toward local features, and an extreme deficit in global/configural processing
      that is not confined to faces. This pattern could be appropriately labeled
      congenital integrative prosopagnosia, and accounts for some, albeit not all,
      cases of face recognition impairments without identifiable brain lesions. Absence
      of face selectivity is evident in both biological markers of face processing,
      fMRI (the fusiform face area [FFA]), and ERPs (N170). Nevertheless, these two
      neural signatures probably manifest different perceptual mechanisms. Whereas the
      N170 is triggered by the occurrence of physiognomic stimuli in the visual field,
      the deficient face-selective fMRI activation in the caudal brain correlates with
      the severity of global processing deficits. This correlation suggests that the
      FFA might be associated with global/configural computation, a crucial part of
      face identification.

PMID- 17214571
TI  - The role of the cerebellum in subsecond time perception: evidence from repetitive
      transcranial magnetic stimulation.
AB  - In three experiments, we investigated the role of the cerebellum in sub- and
      suprasecond time perception by using repetitive transcranial magnetic stimulation
      (rTMS). In Experiment 1, subjects underwent four 8-min 1-Hz rTMS sessions in a
      within-subject design. rTMS sites were the medial cerebellum (real and sham
      rTMS), left lateral cerebellum, and right lateral cerebellum. Following each rTMS
      session, subjects completed a subsecond temporal bisection task (stimuli in the
      range 400-800 msec). Compared with sham rTMS, rTMS applied over the right lateral
      or medial cerebellum induced a leftward shift of the psychophysical function
      (perceived lengthening of time). In Experiment 2, a separate sample of subjects
      underwent the identical rTMS procedure and completed a suprasecond bisection task
      (stimuli in the 1000-2000 msec range). In this experiment, rTMS to the cerebellar
      sites did not produce any significant changes compared with sham rTMS. Experiment
      3 employed a within-subject design to replicate findings from Experiments 1 and
      2. Subjects underwent four rTMS conditions (sub- and suprabisection tasks
      following medial cerebellar and sham rTMS). rTMS induced a significant leftward
      shift of psychophysical function in the subsecond bisection, but not in the
      suprasecond bisection. In this study, we have demonstrated that transient
      cerebellar stimulation can differently affect the ability to estimate time
      intervals below and above a duration of 1 sec. The results of this study provide
      direct evidence for the role of the cerebellum in processing subsecond time
      intervals. This study further suggests that the perception of sub- and
      suprasecond intervals is likely to depend upon distinct neural systems.

PMID- 17214572
TI  - Distinction between perceptual and attentional processing in working memory
      tasks: a study of phase-locked and induced oscillatory brain dynamics.
AB  - Working memory involves the short-term storage and manipulation of information
      necessary for cognitive performance, including comprehension, learning, reasoning
      and planning. Although electroencephalogram (EEG) rhythms are modulated during
      working memory, the temporal relationship of EEG oscillations with the eliciting
      event has not been well studied. In particular, the dynamics of the neural
      network supporting memory processes may be best captured in induced oscillations,
      characterized by a loose temporal link with the stimulus. In order to
      differentiate induced from evoked functional processes, the present study
      proposes a time-frequency analysis of the 3 to 30 Hz EEG oscillatory activity in
      a verbal n-back working memory paradigm. Control tasks were designed to identify
      oscillatory activity related to stimulus presentation (passive task) and focused
      attention to the stimulus (detection task). Evoked theta activity (4-8 Hz) phase
      locked to the visual stimulus was evidenced in the parieto-occipital region for
      all tasks. In parallel, induced theta activity was recorded in the frontal region
      for detection and n-back memory tasks, but not for the passive task, suggesting
      its dependency on focused attention to the stimulus. Sustained induced
      oscillatory activity was identified in relation to working memory in the theta
      and beta (15-25 Hz) frequency bands, larger for the highest memory load. Its late
      occurrence limited to nonmatched items suggests that it could be related to item
      retention and active maintenance for further task requirements. Induced theta and
      beta activities displayed respectively a frontal and parietal topographical
      distribution, providing further functional information on the fronto-posterior
      network supporting working memory.

PMID- 17214576
TI  - Signaling abnormalities in systemic lupus erythematosus as potential drug
      targets.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease
      characterized by T-cell, B-cell, and dendritic cell dysfunction and antinuclear
      autoantibody production. Much of the knowledge that has been gained about SLE in
      recent years is related to molecular signaling abnormalities present in the
      disease. Signaling through the T-cell receptor (TCR) is affected in SLE by
      alterations in the localization, amount, and activity of numerous protein
      kinases. TCR stimulation releases calcium from intracellular stores, which
      triggers an influx of extracellular calcium and activates the transcription of
      many genes, including interleukin-2. Short-term calcium fluxing is exaggerated in
      SLE, but long-term calcium fluxing is diminished and may account for sub-optimal
      interleukin-2 production. SLE T-cells have persistently hyperpolarized
      mitochondria associated with increased mitochondrial mass, high levels of
      reactive oxygen species (ROS) and low levels of ATP, which decrease activation
      induced apoptosis and instead predispose T cells for necrosis, thus stimulating
      inflammation in SLE. The pentose phosphate pathway impacts the mitochondrial
      potential and represents a target for possible intervention. Nitric oxide (NO) is
      a potential link to tie together the signaling and mitochondrial abnormalities in
      SLE. NO-induced mitochondrial biogenesis recapitulates the TCR-stimulated calcium
      fluxing abnormalities of SLE T-cells. Since mitochondria can store calcium, the
      increase in mitochondrial mass may be implicated in the aberrant calcium fluxing
      in SLE T cells. The mammalian target of rapamycin senses the mitochondrial
      potential and regulates calcium release, serving as a novel target of treatment
      of SLE.

PMID- 17214577
TI  - Blockade of chemokine-mediated tissue injury in lupus nephritis.
AB  - Pro-inflammatory chemokines are important mediators of inflammation and
      autoimmune injury. The spatial and temporal expression of chemokines and
      chemokine receptors in the nephritic kidney suggests that targeting the chemokine
      system may represent a valuable approach for anti-inflammatory therapy of lupus
      nephritis. In this review we summarize the available data on the pathogenic role
      of chemokines and chemokine receptors in lupus nephritis and particularly focus
      on epidemiological data in lupus patients and interventional studies with
      chemokine or chemokine receptor antagonists in experimental lupus.

PMID- 17214579
TI  - Viral anti-inflammatory reagents: the potential for treatment of arthritic and
      vasculitic disorders.
AB  - Inflammatory and immune responses are inherent in the development of progressive
      arthritic or vasculitic disorders. Arthritis is frequently associated with
      accelerated forms of vasculitis; atherosclerosis being one form of accelerated
      vasculitis that blocks blood flow causing heart attacks and strokes. The arterial
      supply is central to maintaining normal articular function and acts as a conduit
      for inflammatory (innate) and immune (antigen dependent) cell trafficking in
      joints. The vasculature in some cases can become inflamed in the disease process.
      While treatment of severely debilitating arthritic disorders has improved, some
      current treatments are limited to reducing symptoms while others act as disease
      modifying drugs (DMARDs), but may have limited success. Many current treatments
      also have reported adverse side effects. Vasculitic disorders are similarly
      debilitating with high associated morbidity and mortality and current therapy for
      these disorders is only partially successful. Immune-modifying agents, which
      alter vascular inflammation, thus have potential for application in rheumatologic
      diseases. Viral immune modulating proteins reduce early arterial inflammatory
      responses with associated reductions in atherosclerotic plaque development and
      transplant rejection in a wide range of animal models. A clinical trial utilizing
      one such viral reagent, a secreted myxomaviral serpin, is currently in progress,
      assessing treatment of acute coronary syndrome, a vascular syndrome with marked
      up-regulation of systemic inflammatory responses. In this review we examine viral
      anti-inflammatory proteins as potential therapeutic reagents for arthritic and
      vasculopathic disorders.

PMID- 17214578
TI  - Type I interferon as a target of treatment in SLE.
AB  - Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease
      characterized by the production of antibodies against a spectrum of autoantigens.
      Recent evidence suggests that type-I interferons (IFN-I) are critically involved
      in the pathogenesis of SLE. Initially recognized for their anti-viral properties,
      IFN-I play important roles in immunity and autoimmunity by promoting DC
      maturation, T cell survival, and antibody production. Onset of SLE has been
      reported in patients with hepatitis or neoplastic diseases undergoing treatment
      with recombinant IFN-I while elevated serum IFN-I and IFN-stimulated gene
      expression are found in approximately 2/3 of SLE patients. This interferon
      signature is clinically important as it correlates with disease activity and
      renal as well as CNS involvement. Supporting these findings, genetic
      abnormalities resulting in increased IFN-I production and/or signaling are
      associated with SLE. In view of the accumulating evidence linking IFN-I to the
      pathogenesis of SLE, targeting of IFN-I may be beneficial therapeutically while
      avoiding the side effects associated with conventional immunosuppressive therapy.
      To this end, IFN-I and IFN-producing cells as well as IFN-inducers and molecules
      of the IFN signaling pathway may all serve as potential therapeutic targets.
      Several anti-IFN-I approaches have already shown promising effects in animal
      studies and clinical trials will likely begin in the near future.

PMID- 17214580
TI  - Targeting B cells in SLE: the experience with rituximab treatment (anti-CD20).
AB  - B cells play a central role in the pathogenesis of SLE. Not only do they make
      autoantibodies, but they can provide immunoregulatory controls of T cells,
      dendritic cells, and other B cells, in part through cytokine production. The
      availability of a chimeric monoclonal antibody that targets B cells has made it
      possible to treat SLE by B-cell depletion. Rituximab binds to the B-cell specific
      antigen CD20, and depletes B cells from the peripheral blood and lymphoid
      tissues. A growing number of anecdotal series and case reports suggest that
      rituximab may provide clinical benefit in SLE with acceptable toxicity, although
      the variability in responses of individual patients is not yet fully understood.
      Two large ongoing randomized controlled trials will determine the efficacy of
      rituximab in SLE, both renal and extra-renal, and will inform us better about the
      biology of the B cell in this disease and the effects of B-cell depletion.

PMID- 17214581
TI  - Therapeutic targeting of B lymphocyte stimulator (BLyS) in the rheumatic
      diseases.
AB  - B lymphocyte stimulator (BLyS) is a vital B cell survival factor. Overexpression
      of BLyS in mice can lead to clinical and serological features of systemic lupus
      erythematosus (SLE) and Sjogren's syndrome (SS). Treatment with BLyS antagonists
      of mice with established SLE ameliorates disease progression and enhances
      survival. Moreover, similar treatment of mice with inflammatory arthritis
      ameliorates the ongoing inflammation and subsequent joint destruction. In humans,
      BLyS overexpression is common in patients with several rheumatic diseases,
      including SLE, rheumatoid arthritis (RA), Sjogren's syndrome, scleroderma,
      Wegener's granulomatosis, and ANCA-associated vasculitis. Results from phase-II
      clinical trials with a BLyS antagonist in human SLE and RA have shown the
      antagonist to have biological and clinical activity along with a favorable safety
      profile. These features collectively point to BLyS as an attractive therapeutic
      target in human rheumatic diseases.

PMID- 17214582
TI  - NF-kappaB and rheumatic diseases.
AB  - NF-kappaB is an inducible transcription factor that is controlled by the signal
      activation cascades. NF-kappaB controls a number of genes involved in immuno
      inflammatory responses, cell cycle progression, inhibition of apoptosis, and cell
      adhesion, thus promoting chronic inflammatory responses. In fact, NF-kappaB is
      constitutively activated in some rheumatic conditions such as rheumatoid
      arthritis (RA) and systemic lupus erythematosus (SLE). Interestingly, a number of
      anti-RA compounds have been shown to exhibit anti-NF-kappaB activities. In
      addition, NF-kappaB activation has been linked to carcinogenesis and its
      constitutive activation has been demonstrated in some cancers and leukemias.
      These findings have substantiated the long-standing proposal of the link among
      chronic inflammation, autoimmunity, and carcinogenesis by molecular terms. In
      this review, I have attempted to overview the pathologic involvement of NF-kappaB
      in rheumatic diseases and discuss the feasibility of a therapeutic strategy with
      NF-kappaB and its signaling cascade as novel molecular targets.

PMID- 17214583
TI  - Anti-interleukin-6 receptor antibody therapy in rheumatic diseases.
AB  - In the treatment of rheumatic diseases such as rheumatoid arthritis (RA) or
      systemic onset juvenile idiopathic arthritis (soJIA), new therapies targeting pro
      inflammatory cytokines have been developed. IL-6 is a pleiotropic cytokine with a
      wide range of biological activities including a pro-inflammatory mediator
      activity. Overproduction of IL-6 has been reported to be pathologically involved
      in the rheumatic diseases and, therefore, blockade of IL-6 actions may improve
      the disease. Tocilizumab, a humanized monoclonal antibody against human
      interleukin-6 receptor (IL-6R), inhibits IL-6 binding to IL-6R and specifically
      interferes with IL-6 actions. Castleman's disease is an atypical
      lymphoproliferative disorder caused by the overproduction of IL-6. Tocilizumab
      therapy improves immunological and hematological abnormalities as well as
      systemic inflammatory symptoms including wasting. This translational study also
      confirmed the pathological significance of IL-6 in the disease. RA is a
      representative autoimmune inflammatory disease characterized by bone and
      cartilage destruction in multiple joints. Since IL-6 also plays pathological
      roles in RA, tocilizumab therapy has been introduced to the patients with
      refractory disease and has shown a strong therapeutic effect. Besides Castleman's
      disease and RA, tocilizumab has been shown to be effective for patients with
      soJIA and Crohn's disease. Tocilizumab treatment is generally well tolerated and
      safe. Therefore, tocilizumab can be a promising therapeutic agent for the
      rheumatic diseases in which IL-6 overproduction is pathologically involved.

PMID- 17214584
TI  - Role of PGE2 and EP receptors in the pathogenesis of rheumatoid arthritis and as
      a novel therapeutic strategy.
AB  - Recent progress in understanding the pathogenesis of rheumatoid arthritis (RA) in
      parallel with elucidation of the functional role of the prostaglandin receptor
      subfamily has revealed an important regulatory role of PGE2, in addition to its
      well-known proinflammatory role in the progression of RA. Characteristic features
      of RA are synovial proliferation and pannus formation, which result in the
      destruction of cartilage and bone. Pannus tissue is mainly composed of
      macrophages and fibroblast-like synoviocytes. Both T cell-derived IL-17 and
      macrophage-derived TNF-alpha seem to play a central role in the progression of
      proinflammatory cascades in RA. PGE2 is also produced in response to
      proinflammatory cytokines, which in turn negatively regulates both IL-17 and TNF
      alpha expression and TNF/IL-1-induced activation of fibroblast-like synoviocytes
      through EP2/EP4 receptors, resulting in the modulation of proinflammatory
      cascades. IL-17- and TNF-activated macrophages differentiate into osteoclasts in
      the presence of M-CSF and RANKL expressed by fibroblast-like synoviocytes. PGE2
      binding to EP4 stimulates osteoclastogenesis through enhancing RANKL expression.
      At the same time, PGE2 suppresses osteoclastogenesis by inhibiting M-CSF
      expression of fibroblast-like synoviocytes as well as both IL-17 and IL-17
      induced TNF-alpha expression of macrophages. PGE2-EP4 also activates
      osteoblastogenesis through increasing cbfa1 and osterix, two essential
      transcription factors required for bone formation. The net effect of PGE2 may
      direct toward repair of eroding bone through the suppression of inflammation and
      enhancement of bone remodeling. Here, we discuss a diverse action of PGE2/EP
      receptors and their important regulatory roles in the pathogenesis of RA, which
      may lead to a novel therapeutic strategy.

PMID- 17214585
TI  - Targeting fibrosis in systemic sclerosis.
AB  - Finding effective treatments for patients with systemic sclerosis (SSc) remains
      one of the final frontiers in therapeutic discovery. Although remarkable progress
      has been made in the symptomatic treatment of various organ system
      manifestations, little is available that treats the underlying disease process.
      SSc patients do not respond to many of the medications that provide benefit in
      related diseases, such as systemic lupus erythematosus, polymyositis and chronic
      graft-versus-host disease. Current research has not even clarified whether the
      complex pathogenesis starts primarily in vascular, immunological or connective
      tissues. Herein are discussed selected emerging therapeutics and therapeutic
      approaches designed to target the underlying immunological and fibrotic disease
      processes. Distinctive fibrotic features and data from translational research
      consistently place transforming growth factor-beta (TGFbeta) as a central
      mediator in SSc. The discovery of agents targeting TGFbeta, its activation or its
      intracellular signaling suggest that TGFbeta pathway inhibitors efficacious for
      the treatment of SSc may soon be identified. IL-4 and IL-13 are other fibrotic
      mediators produced during immune activation that might be targeted for SSc
      therapy, and therapeutics targeting these interleukins are also being developed.
      Immune dysregulation, leading to overproduction of these or other fibrotic
      mediators might respond to currently available immunosuppressives: mycophenolate,
      cyclosporine, tacrolimus or sirolimus, alone or in combination. Nucleic acid
      containing immune complexes may also contribute to toll-like receptor mediated
      immune dysregulation in SSc, suggesting that agents targeting the innate immune
      system may ameliorate SSc. Thus, the complexity of SSc pathogenesis provides a
      plethora of targets for urgently needed new therapies.

PMID- 17214586
TI  - Targeting vascular disease in systemic sclerosis.
AB  - Systemic sclerosis (scleroderma, SSc) is a chronic connective tissue disease of
      unknown etiology characterized by progressive fibrosis of the skin and a
      distinctive pattern of internal organ involvement. Excessive fibrosis, vascular
      injury, autoimmunity and inflammation are permanent features of the disease
      process leading to irreversible organ damage and significant morbidity and
      mortality in SSc patients. Recent progress in understanding the pathogenesis of
      SSc as well as diagnostic and therapeutic advances in medicine have made more
      effective treatment strategies possible. So far, therapies targeting vascular
      aspects of SSc have been most successful. This underlines the role of vascular
      injury in the pathogenesis of the disease and raising hopes of significant
      improvement in the management of SSc patients. The aim of this review is to
      summarize recent and potential future treatments of SSc-associated vascular
      disease.

PMID- 17214587
TI  - Recent advances in the treatment of interstitial lung disease in patients with
      polymyositis/dermatomyositis.
AB  - Interstitial lung disease (ILD) develops in 30-50% of patients with
      polymyositis/dermatomyositis (PM/DM) and negatively affects their prognosis. The
      progression of PM/DM-ILD may be acute, subacute, chronic, or chronic becoming
      acute. The histopathological classification of PM/DM-ILD includes non-specific
      interstitial pneumonia (NSIP), organizing pneumonia (OP), diffuse alveolar damage
      (DAD), and usual interstitial pneumonia (UIP) or mixed variations. Some patients
      with acute/subacute interstitial pneumonia (A/SIP), typically with lung histology
      of OP or cellular NSIP, respond favorably to corticosteroid treatment, while
      others do not. Japanese patients with DM, especially those with clinically
      amyopathic DM (C-ADM) and palmar papules, seem to be at a greater risk of
      developing fulminant A/SIP with DAD histology resulting in pneumomediastinum and
      fatal outcome in a few months. An aggressive combination regimen including
      cyclosporine A (or tacrolimus) and cyclophosphamide should be immediately added
      to corticosteroid treatment for such patients. Sequential follow-up examination
      using high-resolution computed tomography (HRCT) of the chest and careful
      monitoring for bacterial and viral infections are essential. However, intensive
      immunosuppression alone may not be sufficient to control fulminant A/SIP, and
      other therapeutic targets, such as fibroblasts, should be considered.

PMID- 17214589
TI  - Longitudinal study of defense mechanisms: late childhood to late adolescence.
AB  - Based on longitudinal data from the Institute of Human Development
      Intergenerational Study, the use and change in defense mechanisms of more than
      150 individuals, as assessed from TAT stories, was studied across ages 11, 12,
      and 18. The findings of this study, based on an earlier generation, were
      generally consistent with cross-sectional findings from current samples, showing
      that the defenses of projection and identification were used more frequently than
      denial at all three ages and that the use of projection and identification
      increased from early to late adolescence. However, unlike current findings, the
      18-year-olds did not show greater use of identification than of projection,
      perhaps due to IQ differences between this community sample and the samples of
      more recent studies.

PMID- 17214590
TI  - Political-economic values and the relationship between socioeconomic status and
      self-esteem.
AB  - Values concerning the distribution of wealth are an important aspect of identity
      for many Americans, and such values may therefore influence how Americans
      experience their own socioeconomic status (SES). Based on this proposition, the
      present research examines political-economic values as a moderator of the
      relationship between SES and self-esteem. Results supported the hypothesis that
      there is a stronger relationship between SES and self-esteem among individuals
      who report relatively inegalitarian values than among individuals who report
      relatively egalitarian values. This result was replicated using both objective
      and subjective measures of SES. Implications of the present findings for the
      study of values and well-being, psychological conflict, and the influence of
      economic factors on self-esteem are discussed.

PMID- 17214591
TI  - Longitudinal effects of hope on depression and anxiety: a latent variable
      analysis.
AB  - This study tested the prospective effects of hope on depression and anxiety using
      a longitudinal design. A sample of 522 college students completed self-report
      measures of hope, depression, and anxiety at three time points, with 1-month
      delays between administrations. Structural equation modeling was employed to test
      two cross-lagged panel models of the reciprocal effects of the Agency and
      Pathways components of hope on depression and anxiety. Results indicated
      statistically significant negative effects for the Agency component of hope on
      later depression but no unique effect of the Pathways component of hope on
      depression. Likewise, Agency showed a statistically significant negative effect
      on later anxiety, but again Pathways had no significant influence on anxiety. In
      both cases, neither depression nor anxiety demonstrated any longitudinal effects
      on either the Agency or Pathways components of hope. Implications of these
      findings are discussed, along with potential directions for future research.

PMID- 17214588
TI  - Ferryl haem protonation gates peroxidatic reactivity in globins.
AB  - Ferryl (Fe(IV)=O) species are involved in key enzymatic processes with direct
      biomedical relevance; among others, the uncontrolled reactivities of ferryl Mb
      (myoglobin) and Hb (haemoglobin) have been reported to be central to the
      pathology of rhabdomyolysis and subarachnoid haemorrhage. Rapid-scan stopped-flow
      methods have been used to monitor the spectra of the ferryl species in Mb and Hb
      as a function of pH. The ferryl forms of both proteins display an optical
      transition with pK approximately 4.7, and this is assigned to protonation of the
      ferryl species itself. We also demonstrate for the first time a direct
      correlation between Hb/Mb ferryl reactivity and ferryl protonation status,
      simultaneously informing on chemical mechanism and toxicity and with broader
      biochemical implications.

PMID- 17214592
TI  - The big seven model of personality and its relevance to personality pathology.
AB  - Proponents of the Big Seven model of personality have suggested that Positive
      Valence (PV) and Negative Valence (NV) are independent of the Big Five
      personality dimensions and may be particularly relevant to personality disorder.
      These hypotheses were tested with 403 undergraduates who completed a Big Seven
      measure and markers of the Big Five and personality pathology. Results revealed
      that PV and NV incrementally predicted personality pathology dimensions beyond
      those predicted by multiple markers of the Big Five. However, factor analyses
      suggested that PV and NV might be best understood as specific, maladaptive
      aspects of positive emotionality and low agreeableness, respectively, as opposed
      to independent factors of personality. Implications for the description of normal
      and abnormal personality are discussed.

PMID- 17214594
TI  - Multimethod longitudinal assessment of temperament in early childhood.
AB  - The present study examined consistency of temperament across situations and time
      in early childhood. On two occasions, 7 months apart, we observed the responses
      of 94 four-year-olds to multiple standard laboratory procedures eliciting
      exuberance, fear, anger, sadness, or interest. In addition, fathers' and mothers'
      reports on children's temperament were obtained. Observed temperament showed
      substantial context specificity, varying across situations within dimensions.
      Structural equation models revealed separate observation and parental perception
      factors and factorial invariance and high stability for most dimensions.
      Stability coefficients based on correlations varied according to level of
      aggregation. Measurement convergence was generally moderate and was lowest for
      negative emotionality. Implications for the assessment of temperament are
      discussed in relation to differences in consistency across dimensions and
      convergence between measures.

PMID- 17214593
TI  - Traits, States, and encoding speed: support for a top-down view of
      neuroticism/state relations.
AB  - Recent theories suggest that trait neuroticism gains its pernicious power
      particularly among individuals less capable of making distinctions concerning
      present reality. Four studies, involving 272 undergraduates, sought to provide
      some basic, assessment-related support for such theories in the context of
      individual differences in choice reaction time, which reflect abilities to make
      distinctions at encoding. Studies 1-3 focused on somatic symptoms, whereas Study
      4 focused on neurotic behaviors and negative affect. As predicted, neuroticism
      consistently interacted with categorization speed in predicting these dependent
      measures. Specifically, neuroticism/outcome relations were robust among
      individuals slow to make distinctions at encoding; by contrast, neuroticism did
      not predict the dependent measures among individuals fast to make distinctions.
      Such data reinforce suggestions that neuroticism is particularly pernicious among
      individuals less capable of making distinctions at encoding.

PMID- 17214595
TI  - The spirited, the observant, and the disheartened: social concepts of optimism,
      realism, and pessimism.
AB  - The social concepts of optimism, pessimism, and realism were investigated by
      assessing the prototypical acts (thoughts, feelings, goals, and actions) that
      laypersons assign to optimists, pessimists, and realists responding to a
      controllable and an uncontrollable situation. Optimists and realists, but not
      pessimists, were seen as adjusting their behavior to the situation. However,
      whereas optimists were characterized by flexibility in thoughts and feelings but
      invariance in goals and actions (i.e., they pursued their goals in both
      controllable and uncontrollable situations), the act profiles assigned to
      realists varied on all of these dimensions. The profile assigned to pessimists
      was characterized by cognitive, affective, motivational, and behavioral
      invariance, encompassing negative construals of the situation, giving up, and a
      focus on distress.

PMID- 17214596
TI  - L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug.
AB  - L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxydopa) is a synthetic
      catecholamino acid. When taken orally, L-DOPS is converted to the sympathetic
      neurotransmitter, norepinephrine (NE), via decarboxylation catalyzed by L
      aromatic-amino-acid decarboxylase (LAAAD). Plasma L-DOPS levels peak at about 3
      h, followed by a monoexponential decline with a half-time of 2 to 3 h. Plasma
      levels of NE and of its main neuronal metabolite, dihydroxyphenylglycol (DHPG)
      peak approximately concurrently but at much lower concentrations. The relatively
      long half-time for disappearance of L-DOPS from plasma, compared to that of NE,
      explains their very different attained plasma concentrations. In patients with
      neurogenic orthostatic hypotension, L-DOPS increases blood pressure and
      ameliorates orthostatic intolerance. Inhibition of LAAAD, such as by treatment
      with carbidopa, which does not penetrate the blood-brain barrier, prevents the
      blood pressure effects of the drug, indicating that L-DOPS increases blood
      pressure by augmenting NE production outside the brain. Patients with pure
      autonomic failure (which usually entails loss of sympathetic noradrenergic
      nerves), and patients with multiple system atrophy (in which noradrenergic
      innervation remains intact) have similar plasma NE responses to L-DOPS. This
      suggests mainly non-neuronal production of NE from L-DOPS. L-DOPS is very
      effective in treatment of deficiency of dopamine-beta-hydroxylase (DBH), the
      enzyme required for conversion of dopamine to NE in sympathetic nerves. L-DOPS
      holds promise for treating other much more common conditions involving decreased
      DBH activity or NE deficiency, such as a variety of syndromes associated with
      neurogenic orthostatic hypotension.

PMID- 17214597
TI  - Preclinical studies with adrenomedullin and its binding protein as cardiovascular
      protective agents for hemorrhagic shock.
AB  - Traumatic injury is a major, largely unrecognized public health problem in the US
      that cuts across race, gender, age, and economic boundaries. The resulting loss
      of productive life years exceeds that of any other disease, with societal costs
      of $469 billion annually. Most trauma deaths result either from insufficient
      tissue perfusion due to excessive blood loss, or the development of inflammation,
      infection, and vital organ damage following resuscitation. Clinical management of
      hemorrhagic shock relies on massive and rapid infusion of fluids to maintain
      blood pressure. However, the majority of victims with severe blood loss do not
      respond well to fluid restoration. The development of effective strategies for
      resuscitation of traumatic blood loss is therefore critically needed. We have
      recently discovered that the vascular responsiveness to a recently-discovered
      potent vasodilatory peptide, adrenomedullin (AM) is depressed after severe blood
      loss, which may be due to downregulation of a novel specific binding protein, AM
      binding protein-1 (AMBP-1). Using three different animal models of hemorrhage
      (controlled hemorrhage with large volume resuscitation, controlled hemorrhage
      with low volume resuscitation, and uncontrolled hemorrhage with minimum
      resuscitation), we have shown that cell and organ injury occurs after hemorrhage
      despite fluid resuscitation. Administration of AM/AMBP-1 significantly improves
      cardiac output, heart performance and tissue perfusion, attenuates hepatic and
      renal injury, decreases pro-inflammatory cytokines, prevents metabolic acidosis,
      and reduces hemorrhage-induced mortality. Thus, administration of AM/AMBP-1
      appears to be a novel and useful approach for restoring cardiovascular responses,
      preventing organ injury, and reducing mortality after hemorrhagic shock.

PMID- 17214598
TI  - Sulodexide: a renewed interest in this glycosaminoglycan.
AB  - Glycosaminoglycans (GAGs) are the most abundant group of heteropolysaccharides
      found in the body. These long unbranched molecules contain a repeating
      disaccharide unit. GAGs are located primarily in the extracellular matrix or on
      the surface of cells. These molecules serve as lubricants in the joints while at
      the same time providing structural rigidity to cells. Sulodexide is a highly
      purified glycosaminoglycan composed of a fast mobility heparin fraction as well
      as dermatan sulfate. Sulodexide differs from other glycosaminoglycans, like
      heparin, by having a longer half-life and a reduced effect on systemic clotting
      and bleeding. In addition, sulodexide demonstrates a lipolytic activity that is
      increased in comparison to heparin. Oral administration of sulodexide results in
      the release of tissue plasminogen activator and an increase in fibrinolytic
      activities. An increasing body of research has demonstrated the safety and
      efficacy of sulodexide in a wide range of vascular pathologies.

PMID- 17214599
TI  - IB-MECA and cardioprotection.
AB  - The adenosine A(3) receptor plays an important role in ischemic preconditioning.
      Activation of the adenosine A(3) receptor with its agonists induces both early
      and late pharmacological preconditioning through various mechanisms. As the first
      potent and selective adenosine A(3) receptor agonist, IB-MECA (N(6)-(3
      iodobenzyl)-adenosine-5'-N-methylcarboxamide) has been demonstrated to induce
      cardioprotection against myocardial ischemia/reperfusion injury when given before
      onset of ischemia by triggering pharmacological preconditioning. More
      importantly, IB-MECA can also protect the heart even when administered at the
      onset of reperfusion after ischemia, indicating a strong likelihood that the drug
      may be useful for the treatment of patients with acute myocardial infarction.
      However, since IB-MECA has been reported to have lethal effects at higher
      concentrations, and may cause systemic hypertension in some species, further
      studies are needed to find the best treatment strategy to increase its
      therapeutic potential.

PMID- 17214600
TI  - Pharmacological effects of AVE 0991, a nonpeptide angiotensin-(1-7) receptor
      agonist.
AB  - In the last 20 years, our understanding of the physiopathology of the renin
      angiotensin system (RAS) has expanded dramatically. Basic and clinical studies
      showed that this system includes several other components in addition to renin,
      angiotensin (Ang) II, an-giotensin-converting enzyme (ACE), and Ang II receptors.
      One of the most interesting new members of RAS is the heptapeptide Ang-(1-7).
      Many in vitro and in vivo studies have proven that this peptide plays several
      beneficial effects in the cardiovascular system, which are often opposite to the
      effects elicited by the main component of the RAS, Ang II. In addition, the
      recent discovery of the main enzyme involved in the Ang-(1-7) production, ACE2
      and the description of the Ang-(1-7) receptor Mas reinforced the biological
      relevance of this peptide. These findings raised the possibility to develop new
      drugs based on the ACE2-Ang-(1-7)-Mas axis and directed to cardiovascular and 
      related diseases. The development of AVE 0991, a nonpeptide Ang-(1-7) receptor
      Mas agonist, represents an important step for exploration of the effects of Ang
      (1-7) and testing of its potential as a cardiovascular drug. Among advantages of
      this compound in comparison with Ang-(1-7) is the fact that it is orally active
      and is expected to be resistant to proteolytic enzymes, circumventing an
      important problem associated with the use of peptides. This article briefly
      reviews in vitro and in vivo cardiovascular and renal effects of AVE 0991.
      Moreover, we are pointing to the evidence that ACE2-Ang-(1-7)-Mas axis may
      represent a putative target for the development of new cardiovascular drugs.

PMID- 17214601
TI  - Potential protective properties of a stable, slow-releasing nitric oxide donor,
      GEA 3175, in the lung.
AB  - Nitric oxide (NO), is known to exert vasodilatory, bronchodilatory, and
      antiplatelet effects, and quantitative or functional NO deficiency has been
      implicated in various cardio-vascular and airway diseases. NO donors, which are
      drugs capable of releasing NO either spontaneously or tissue-dependently,
      represent a way of increasing NO. Here, we review our current understanding of
      the NO donor, GEA 3175, 1,2,3,4-oxatriazolium, 3-(3-chloro-2-methylphenyl)-5
      [[(methylphenyl)sulphonyl]amino], hydroxide inner salt. GEA 3175 is a mesoionic 3
      aryl substituted oxatriazole-5-imine derivative, which is a potent, stable, slow
      releasing NO donor with important actions in various organ systems. In isolated
      guinea pig trachea, rat bronchi and bovine and human small bronchioles, GEA 3175
      induces potent, long-lasting relaxation. In vivo, in sensitized guinea pigs, GEA
      3175 protects against antigen-induced bronchoconstriction. GEA 3175 also exerts
      potent vasodilatory properties. In isolated human pulmonary arteries, GEA 3175
      induces relaxation which is long-lasting and more potent than in airways. In
      isolated systemic arteries, GEA 3175 is also a potent vasodilator. By intravenous
      infusion GEA 3175 reduces blood pressure similarly to nitroglycerin. Vascular and
      bronchiolar relaxations were shown to be mediated via NO dependent pathways. GEA
      3175 is also a potent anti-inflammatory agent. Functions of polymorphnuclear
      cells (PMNs) such as leucotriene B(4) (LTB(4)) - synhesis, chemotaxis and
      superoxide (O(-) (2)) production are inhibited by GEA 3175. GEA3175 also inhibits
      upregulation of E-selectin in human umbilical vein endothelial cells (HUVECs) and
      hence adhesion of neutrophils. Another action of GEA 3175 on the endothelium is
      inhibition of prostacyclin release. Finally, GEA 3175 has been demonstrated to be
      an antiplatelet agent. Thrombin-induced platelet aggregation was inhibited by GEA
      3175 in a cyclic GMP- and vasodilator-stimulated phosphoprotein (VASP)
      phosphorylation-dependent manner. Thus, GEA 3175 has been demonstrated to exert
      bronchodilatory, pulmonary vasodilatory, antiplatelet as well as anti
      inflammatory actions. Given these actions GEA 3175 may represent a potentially
      useful drug. The exact mechanism whereby GEA 3175 releases NO is, however, still
      unknown. In addition, most of the studies so far have been performed in isolated
      tissue preparations. Clearly, further in vivo studies involving animal models are
      required to clarify safety issues and whether GEA 3175 can be used in the
      treatment of pulmonary hypertension and/or airway diseases.

PMID- 17214602
TI  - The many faces of H89: a review.
AB  - H89 is marketed as a selective and potent inhibitor of protein kinase A (PKA).
      Since its discovery, it has been used extensively for evaluation of the role of
      PKA in the heart, osteoblasts, hepatocytes, smooth muscle cells, neuronal tissue,
      epithelial cells, etc. Despite the frequent use of H89, its mode of specific
      inhibition of PKA is still not completely understood. It has also been shown that
      H89 inhibits at least 8 other kinases, while having a relatively large number of
      PKA-independent effects which may seriously compromise interpretation of data.
      Thus, while recognizing its kinase inhibiting properties, it is advised that H89
      should not be used as the single source of evidence of PKA involvement. H-89
      should be used in conjunction with other PKA inhibitors, such as Rp-cAMPS or PKA
      analogs.

PMID- 17214603
TI  - Therapeutic use of citrulline in cardiovascular disease.
AB  - L-citrulline is the natural precursor of L-arginine, substrate for nitric oxide
      synthase (NOS) in the production of NO. Supplemental administration L-arginine
      has been shown to be effective in improving NO production and cardiovascular
      function in cardiovascular diseases associated with endothelial dysfunction, such
      as hypertension, heart failure, atherosclerosis, diabetic vascular disease and
      ischemia-reperfusion injury, but the beneficial actions do not endure with
      chronic therapy. Substantial intestinal and hepatic metabolism of L-arginine to
      ornithine and urea by arginase makes oral delivery very ineffective.
      Additionally, all of these disease states as well as supplemental L-arginine
      enhance arginase expression and activity, thus reducing the effectiveness of L
      arginine therapy. In contrast, L-citrulline is not metabolized in the intestine
      or liver and does not induce tissue arginase, but rather inhibits its activity. L
      citrulline entering the kidney, vascular endothelium and other tissues can be
      readily converted to L-arginine, thus raising plasma and tissue levels of L
      arginine and enhancing NO production. Supplemental L-citrulline has promise as a
      therapeutic adjunct in disease states associated with L-arginine deficiencies.

PMID- 17214606
TI  - Metabolic drug interactions with newer antipsychotics: a comparative review.
AB  - Newer antipsychotics introduced in clinical practice in recent years include
      clozapine, risperidone, olanzapine, quetiapine, sertindole, ziprasidone,
      aripiprazole and amisulpride. These agents are subject to drug-drug interactions
      with other psychotropic agents or with medications used in the treatment of
      concomitant physical illnesses. Most pharmacokinetic interactions with newer
      antipsychotics occur at the metabolic level and usually involve changes in the
      activity of the major drug-metabolizing enzymes involved in their
      biotransformation, i.e. the cytochrome P450 (CYP) monooxygenases and/or uridine
      diphosphate-glucuronosyltransferases (UGT). Clozapine is metabolized primarily by
      CYP1A2, with additional contribution by other CYP isoforms. Risperidone is
      metabolized primarily by CYP2D6 and, to a lesser extent, CYP3A4. Olanzapine
      undergoes both direct conjugation and CYP1A2-mediated oxidation. Quetiapine is
      metabolized by CYP3A4, while sertindole and aripiprazole are metabolized by
      CYP2D6 and CYP3A4. Ziprasidone pathways include aldehyde oxidase-mediated
      reduction and CYP3A4-mediated oxidation. Amisulpride is primarily excreted in the
      urine and undergoes relatively little metabolism. While novel antipsychotics are
      unlikely to interfere with the elimination of other drugs, co-administration of
      inhibitors or inducers of the major enzymes responsible for their metabolism may
      modify their plasma concentrations, leading to potentially significant effects.
      Most documented metabolic interactions involve antidepressant and anti-epileptic
      drugs. Of a particular clinical significance is the interaction between
      fluvoxamine, a potent CYP1A2 inhibitor, and clozapine. Differences in the
      interaction potential among the novel antipsychotics currently available may be
      predicted based on their metabolic pathways. The clinical relevance of these
      interactions should be interpreted in relation to the relative width of their
      therapeutic index. Avoidance of unnecessary polypharmacy, knowledge of the
      interaction profiles of individual agents, and careful individualization of
      dosage based on close evaluation of clinical response and, possibly, plasma drug
      concentrations are essential to prevent and minimize potentially adverse drug
      interactions in patients receiving newer antipsychotics.

PMID- 17214607
TI  - The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in
      cultured primary human hepatocytes.
AB  - The aim of this study was to evaluate the in vitro inductive potential of six
      commonly used trade herbal products on CYP1A2, CYP2D6 and CYP3A4 metabolic
      activities. Herbal components were extracted from the trade products in a way
      that ensured a composition equal to that present in the original product. Primary
      human hepatocytes and specific CYP substrates were used. Classic inducers were
      used as positive controls and herbal extracts were added in in vivo-relevant
      concentrations. Metabolites were determined by high performance liquid
      chromatography (HPLC). St. John's wort and common valerian were the strongest
      inducing herbs. In addition to induction of CYP3A4 by St. John's wort, common
      valerian and Ginkgo biloba increased the activity of CYP3A4 and 2D6 and CYP1A2
      and 2D6, respectively. A general inhibitory potential was observed for horse
      chestnut, Echinacea purpurea and common sage. St. John's wort inhibited CYP3A4
      metabolism at the highest applied concentration. Horse chestnut might be a herb
      with high inhibition potentials in vivo and should be explored further at lower
      concentrations. We show for the first time that G. biloba may exert opposite and
      biphasic effects on CYP1A2 and CYP2D6 metabolism. Induction of CYP1A2 and
      inhibition of CYP2D6 were found at low concentrations; the opposite was observed
      at high concentrations. CYP2D6 activity, regarded generally as non-inducible, was
      increased by exposure to common valerian (linear to dose) and G. biloba (highest
      concentration). An allosteric activation is suggested. From the data obtained, G.
      biloba, common valerian and St. John's wort are suggested as candidates for
      clinically significant CYP interactions in vivo.

PMID- 17214608
TI  - Increased expression ratio of Bcl-2/Bax is associated with crocin-mediated
      apoptosis in bovine aortic endothelial cells.
AB  - Crocin, extracted and purified from Gardenia jasminoids Ellis in our laboratory,
      has been reported to have antioxidative, hypolipidaemic and anti
      atherosclerorotic effects. However, the underlying molecular mechanisms by which
      crocin acts as a cytoprotective agent remain to be elucidated. In the present
      study, we examined the mechanisms of crocin, the digentiobiosyl ester of
      crocetin, on bovine aortic endothelial cell apoptosis induced by hydrogen
      peroxide (H2O2). The cells were obtained from the thoracic aorta of newborn
      calves, and apoptosis was induced by 200 microM H2O2. Before addition of H2O2,
      the cells were pretreated with different concentrations of crocin for 6 hr. After
      incubation of the cells with H2O2, a comparative reverse transcriptase-polymerase
      chain reaction-based repeated amplification protocol assay was used to determine
      the ratio of bcl-2/bax mRNA expression, and cells loaded with fluo-3/AM were
      subjected to laser scanning confocal microscopy for detection of intracellular
      calcium ([Ca2+]i) levels. Treatment of the cells with H2O2 alone decreased the
      ratio of bcl-2/bax expression to almost twice of those of untreated cells (from
      0.33+/-0.05 to 0.16+/-0.02). In the presence of 1 and 10 microM crocin, the
      ratios were enhanced when compared with H2O2 alone respectively (from 0.16+/-0.02
      to 0.58+/-0.04, 1.18+/-0.13). The treatment of cells with crocin alone had little
      effect on the value of this ratio. In the presence or absence of extracellular
      Ca2+, H2O2 could induce intracellular calcium elevation not only in the elevation
      presence of extracellular Ca2+ (Hanks), but also without extracellular calcium
      present (D-Hanks). But the extent of [Ca2+]i under conditions lacking
      extracellular calcium is less. Crocin concentration dependently inhibited the
      [Ca2+]i elevation induced by H2O2 under these two conditions. Our data suggest
      that crocin may exert anti-atherosclerotic effects by increasing the expression
      ratio of bcl-2/bax, as a result, inhibiting the bovine aortic endothelial cell
      apoptosis that plays an important role in the initiation and progression of
      atherosclerosis.

PMID- 17214609
TI  - N,N-diacetyl-L-cystine improves endothelial function in atherosclerotic Watanabe
      heritable hyperlipidaemic rabbits.
AB  - N,N-diacetyl-L-cystine (DiNAC), a novel immunomodulator, stimulates contact
      sensitivity/delayed type hypersensitivity reactions in mice induced by oxazolone
      and reduces atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits.
      Forty-week-old WHHL rabbits were given DiNAC (3 micromol/kg per day) for 8 weeks,
      and endothelium-mediated dilatation was investigated in vivo using pulse wave
      analysis. A significant improvement in endothelial function was found after 3
      weeks of treatment, which was further improved after 8 weeks. For experiments on
      isolated blood vessels, 40-week-old rabbits were treated for 3 weeks. Treatment
      did not affect plasma lipid levels. At termination, aortic rings from the
      thoracic and abdominal aorta were contracted with phenylephrine in vitro.
      Concentration-effect curves to acetylcholine and the calcium ionophore A 23187
      were used to measure endothelium-mediated vasodilatation, and nitroprusside to
      elicit endothelium-independent relaxations. Abdominal aorta relaxations were
      generally larger than in thoracic aorta. DiNAC improved endothelium-dependent
      relaxations in the abdominal but not in the thoracic aorta. This effect was
      independent of the degree of atherosclerosis. It is concluded that DiNAC improved
      endothelial function in atherosclerotic rabbit arteries in vivo and in vitro, and
      may represent a new treatment modality for atherosclerosis-related diseases.

PMID- 17214610
TI  - Curcumin and kolaviron ameliorate di-n-butylphthalate-induced testicular damage
      in rats.
AB  - The present study was carried out to evaluate the ameliorative effects of
      kolaviron (a biflavonoid from the seeds of Garcinia kola) and curcumin (from the
      rhizome, Curcuma longa L.) on the di-n-butylphthalate (DBP)-induced testicular
      damage in rats. Administration of DBP to rats at a dose of 2 g/kg for 9 days
      significantly decreased the relative testicular weights compared to the controls,
      while the weights of other organs remained unaffected. Curcumin or kolaviron did
      not affect all the organ weights of the animals. While only DBP treatment
      significantly increased the testicular malondialdehyde level and gamma-glutamyl
      transferase activity (gamma-GT), it markedly decreased glutathione level, the
      testicular catalase, glucose-6-phosphate dehydrogenase, superoxide dismutase,
      sperm gamma-GT activities and serum testosterone level compared to the control
      group. Data on cauda epididymal sperm count and live/dead ratio were not
      significantly affected in the DBP-treated rats. Alone, DBP treatment resulted in
      a 66% decrease in spermatozoa motility and a 77% increase in abnormal spermatozoa
      in comparison to control. DBP-treated rats showed marked degeneration of the
      seminiferous tubules with necrosis and defoliation of spermatocytes. The DBP
      induced injuries in biochemical, spermatological parameters and histological
      structure of testis were recovered by treatment with kolaviron or curcumin. The
      pattern in the behaviour of these compounds might be correlated with their
      structural variations. Our results indicate that kolaviron and curcumin protect
      against testicular oxidative damage induced by DBP. The chemoprotective effects
      of these compounds may be due to their intrinsic antioxidant properties and as
      such may prove useful in combating phthalate-induced reproductive toxicity.

PMID- 17214611
TI  - Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone
      releasing factor analogue.
AB  - TH9507, an analogue of human growth hormone-releasing factor (hGRF1-44NH2)
      minimally modified by addition of a trans-3-hexenoyl moiety to Tyr1 of the amino
      acid sequence, was found to be resistant to dipeptidyl aminopeptidase-IV
      deactivation. Compared to natural hGRF1-44NH2, the modification slowed the in
      vitro degradation of the peptide in rat, dog and human plasma and prolonged the
      in vivo plasma elimination kinetics of immunoreactive TH9507. Plasma growth
      hormone and insulin-like growth factor-1 (IGF-1) markedly increased in pigs, rats
      and dogs after daily repeat intravenous or subcutaneous injections of TH9507 at
      doses up to 600 microg/kg. Subchronic toxicity studies in rats and dogs with
      TH9507 treatment for up to 4 months showed a significant, but not dose-related,
      increase in body weight gain associated with increased biomarker response.
      Although TH9507 was well tolerated by both rats and dogs, a more pronounced
      anabolic effect and more evident (reversible) adverse effects (liver and kidney
      findings, anaemia, clinical chemistry changes, organ weight effects) were
      observed in dogs after repeat daily subcutaneous injections, which were
      attributed to prolonged exposure to supraphysiological levels of growth hormone
      and/or IGF-1. In both rats and dogs, toxicokinetic evaluations indicated that
      exposure to immunoreactive TH9507 was dose related after both routes of
      administration. The apparent elimination t1/2 in dogs ranged from 21 to 45 min.
      In conclusion, TH9507 is a modified hGRF peptide having enhanced potency and
      duration of action. The adverse treatment-related effects in dogs appear to be
      associated with sustained exposure to supraphysiological levels of growth hormone
      and IGF-1 induced by prolonged TH9507 treatment.

PMID- 17214612
TI  - Amiodarone induces angiotensinogen gene expression in lung alveolar epithelial
      cells through activation protein-1.
AB  - Previous work from this laboratory has shown that amiodarone induces alveolar
      epithelial cell apoptosis that was abrogated by antagonists of angiotensin II. In
      this study, amiodarone up-regulated angiotensinogen mRNA and protein in primary
      cultures of rat type II pneumocytes and in the human A549 cell line. The
      mechanism of amiodarone-induced angiotensinogen expression was studied in A549
      cells with a human angiotensinogen promoter-luciferase reporter
      (angiotensinogen/luciferase). Amiodarone (3 microg/ml) induced both
      angiotensinogen/luciferase and endogenous angiotensinogen mRNA; the latter was
      completely blocked by actinomycin-D. Amiodarone did not affect the half-life of
      endogenous angiotensinogen mRNA. Deletion analyses of angiotensinogen/luciferase
      identified at least two amiodarone-responsive domains in the angiotensinogen
      promoter between -350 to -260 bp and -203 to -46 bp. DNA/Protein array and
      electrophoretic mobility shift assays showed that amiodarone increases DNA
      binding of both activation protein-1 and STAT-5 transcription factors. Site
      directed mutagenesis of three IL-6-responsive signal transducer activator of
      transcription (STAT) binding sites within the amiodarone-response domains had no
      effect on amiodarone-induced angiotensinogen/luciferase expression. In contrast,
      amiodarone-induced angiotensinogen/luciferase expression was abrogated by a
      dominant-negative fos construct and was stimulated over five times by c-fos and c
      jun expressed together but not separately. Mutagenesis of the activation protein
      1 binding site at -15 to -12 bp completely eliminated the response to amiodarone.
      These data show that activation protein-1 family transcription factors mediate
      amiodarone-induced angiotensinogen expression in human alveolar epithelial cells
      and identify an activation protein-1 site, located between the TATA (DNA
      sequence) box and the transcription initiation site, that is required for the
      response.

PMID- 17214613
TI  - Indorenate improves motor function in rats with chronic spinal cord injury.
AB  - The effect of indorenate (5-methoxytryptamine, beta-methyl carboxylate
      hydrochloride), a 5-HT1A agonist, was investigated on the motor performance of
      rats with chronic spinal cord injury. Four months after a ninth thoracic
      vertebrae spinal cord contusion, 29 rats were randomly allocated into two groups:
      saline solution and indorenate-treated animals with daily doses incremented at
      weekly intervals. The locomotor performance of all rats was measured by the
      Basso, Beattie, and Bresnahan (BBB) rating scale. The results showed that at the
      end of the treatment, the motor activity of indorenate group was significantly
      better than that presented by saline solution group. The 80% of indorenate,
      (against 15% of saline solution) did not show detriment on motor activity. When
      we analysed the motor activity of rats with basal BBB lower than 10, a
      significant improvement of motor recovery in indorenate-treated animals was
      observed. The benefits observed in locomotor function at low doses followed by
      increasing doses could be associated with pharmacological treatment by
      indorenate, a well-known 5-HT1A receptor agonist. Our results suggest a potential
      mechanism by which serotonergic agents may improve motor function in rats with
      chronic spinal cord injury.

PMID- 17214615
TI  - C-reactive protein and aortic stiffness in patients with idiopathic dilated
      cardiomyopathy.
AB  - BACKGROUND: Previous studies have shown an association between C-reactive protein
      (CRP)and arterial stiffness in most cardiovascular diseases. Increased CRP levels
      and arterial stiffness have been considered independent predictors of
      cardiovascular mortality in cardiovascular disease and even in the general
      population. OBJECTIVE: The aim of this study was to investigate the relationship
      between CRP, a marker of systemic inflammation and aortic stiffness in patients
      with idiopathic dilated cardiomyopathy (DCMP). METHODS: Serum CRP levels and
      aortic stiffness parameters were measured in DCMP patients (n= 37) and age- and
      gender-matched control subjects (n= 30). High-sensitivity CRP levels were
      determined by an immunonephelometry assay. Aortic strain (AS) and aortic
      distensibility (AD) were calculated from the aortic diameters measured using M
      mode echocardiography and blood pressure obtained by sphygmomanometry. RESULTS:
      Serum levels of CRP in DCMP patients were higher than in the control subjects
      (5.47 +/- 2.06 mg/L and 2.35 +/- 0.47 mg/L, P < 0.001, respectively). AS and AD
      were significantly decreased in DCMP patients compared to the controls (P < 0.001
      and P < 0.001, respectively). There were positive correlations between CRP, and
      (r = 0.3.64, P = 0.027) smoking (r = 0.3.56, P = 0.024), and increasing age (r =
      0.587, P < 0.001), and negative correlations between CRP, and DBP (r =-0.485, P <
      0.001), diameter change (DC; r =-0.493, P < 0.001), AS (r =-0.526, P < 0.001),
      and AD (r =-0.626, P < 0.001). CONCLUSION: We have shown that there is a
      significant relation between high serum CRP levels and impaired aortic stiffness
      in patients with idiopathic DCMP. These findings may indicate an important role
      of CRP in the pathogenesis of impaired aortic stiffness in idiopathic DCMP.

PMID- 17214616
TI  - Relationship between slow coronary flow and left atrial appendage blood flow
      velocities.
AB  - AIMS: This study was undertaken to assess whether slow coronary flow (SCF)is
      related to low left atrial appendage (LAA) blood flow velocities. METHODS: Study
      subjects consist of 44 patients with SCF and 11 volunteer subjects with normal
      coronary angiogram. The diagnosis of SCF was made using the TIMI frame count
      method. The blood flow velocities were obtained by placing a pulsed-wave Doppler
      sample volume inside the proximal third of the LAA. RESULTS: The mean LAA
      emptying velocities (MEV)were significantly lower in patients than control
      subjects (34.5 +/- 9.9 cm/sec vs 84.0 +/- 12.1 cm/sec; P < 0.001). In bivariate
      analysis, significant correlation was found between MEV, and systolic pulmonary
      venous flow, mean TIMI frame count, deceleration time, and isovolumetric
      relaxation time (P < 0.05). By multiple linear regression analysis, mean TIMI
      frame count (beta=-0.865, P < 0.001) was identified as independent predictors of
      MEV. CONCLUSION: This study indicates that SCF phenomenon may be related to low
      LAA blood flows.

PMID- 17214617
TI  - Warfarin therapy initiated before is more beneficial than after transesophageal
      echocardiography detected left atrial thrombus.
AB  - OBJECTIVE: Warfarin anticoagulation significantly reduces the risk of
      thromboembolism in patients with atrial fibrillation (AF). However, there are
      many patients with AF who begin anticoagulation only after left atrial thrombus
      (LAT) is detected by transesophageal echocardiography (TEE). The impact of
      anticoagulation in these patients has not been clearly described. The purpose of
      this study was to investigate the incidence of cerebrovascular accident (CVA)
      among AF patients who began warfarin before LAT was detected by TEE compared to
      those who began warfarin only after TEE demonstrated LAT and those did not
      receive warfarin at any point. METHOD: Of the 90 consecutive AF patients with LAT
      (male 48, female 42, age 71.5 +/- 10.1 years), 49 began warfarin more than 3
      weeks before TEE (Group I); 29 began warfarin after TEE (Group II); and 12 did
      not receive warfarin at all (Group III). RESULTS: The incidence of CVA in Group I
      (14%, 7/49, prior CVA 5, new CVA after TEE 2) was significantly lower than Group
      II (45%, 13/29, prior CVA 10, new CVA after TEE 3, P = 0.006) and III (42%, 5/12,
      prior CVA 3, new CVA after TEE 2, P = 0.047). Patients with persistent LAT had
      significantly higher incidence (64% vs 23%, P = 0.024) of CVA and lower CVA free
      survival than those with resolved LAT. CONCLUSION: The incidence of CVA among AF
      patients, who began warfarin before LAT detection, is significantly lower than
      those who began warfarin after LAT detection as well as those who did not receive
      warfarin at all.

PMID- 17214618
TI  - Effect of preload alterations by hemodialysis on the time interval between the
      onsets of early diastolic mitral inflow and annular waveforms.
AB  - BACKGROUND: The T(Ea-E), which is defined as the time interval between the peak
      of the R-wave and the onset of early diastolic mitral annular waveform (T(Ea))
      minus the time interval between the peak of the R-wave and the onset of early
      diastolic mitral inflow waveform (T(E)), is recently proposed as a useful index
      of left ventricular (LV) relaxation. The aim of this study is to determine
      whether the T(Ea-E) is preload-independent. METHODS: Twenty hemodialysis (HD)
      patients (9 men; age 64 +/- 9 years) underwent echocardiography 1 hour before and
      1 hour after HD was studied. RESULTS: After HD, the body weight (P < 0.001),
      early transmitral filling wave peak velocity (E) (P < 0.001), the ratio of E to
      late transmitral filling wave peak velocity (P = 0.011), the early diastolic
      mitral anuular velocity (Ea) (P = 0.002), E/Ea (P = 0.026), and T(Ea-E) (P <
      0.001) decreased significantly, and the T(Ea) (P = 0.047) and T(E) (P = 0.005)
      increased significantly. In addition, T(Ea-E) had a significant negative
      correlation with Ea either before (r =-0.457, P = 0.043) or after HD (r =-0.637,
      P = 0.003). CONCLUSIONS: T(Ea-E), as well as Ea, was a preload-dependent
      relaxation index. The preload dependence of this newer Doppler parameter limited
      its utility in evaluating LV diastolic function in HD patients.

PMID- 17214619
TI  - Correlation of the myocardial performance index with conventional
      echocardiographic indices of systolic and diastolic function: a study in cardiac
      surgical patients.
AB  - BACKGROUND: The aim of this investigation was to compare the myocardial
      performance index (MPI), a Doppler-derived parameter of global ventricular
      function, with standard echocardiographic measures of systolic and diastolic
      function in patients undergoing coronary artery bypass graft (CABG) surgery.
      METHODS: Complete two-dimensional and Doppler examinations were performed on 46
      CABG patients after induction of anesthesia (baseline), 15 minutes
      postcardiopulmonary bypass (CPB), and at the end of the surgical procedure.
      RESULTS: A strong inverse correlation between MPI and both fractional area change
      (adjusted r(2)= 0.588-0.802) and ejection fraction (adjusted r(2)= 0.576-0.656,
      both P < 0.001) of the left ventricle was observed throughout the intraoperative
      period. Following CPB, a weaker correlation was observed between MPI and overall
      diastolic heart function classification (adjusted r(2)= 0.224-0.268, P <0.001).
      Weak, though statistically significant, correlations were observed between MPI
      and deceleration time (P < 0.05), peak atrial reversal (AR) wave velocity (P < or
      =0.002), and duration of the AR wave (P < 0.05). CONCLUSION: Our data suggest
      that the MPI correlates well with standard echocardiographic measures of systolic
      function and modestly well with overall diastolic heart function classification.
      The MPI may be a useful, complementary marker of global left ventricular function
      in patients undergoing CABG surgery.

PMID- 17214620
TI  - The effect of successful electrical cardioversion on left ventricular diastolic
      function in patients with persistent atrial fibrillation: a tissue Doppler study.
AB  - BACKGROUND: Changes in mitral inflow and pulmonary venous flow after electrical
      cardioversion (ECV) in patients with persistent atrial fibrillation (AF) were
      showed in many former studies. In our study we investigated the effects of ECV on
      diastolic parameters by using tissue Doppler imaging (TDI) in patients with
      persistent AF. METHODS: Forty-one (24 women) consecutive patients underwent
      successful elective ECV for nonvalvular persistent AF, and maintained sinus
      rhythm for 1 month were enrolled to the study. Transthoracic echocardiography was
      applied to all patients before, 24 hours after and 1 month after ECV. Mitral
      annular TDI parameters were also measured with mitral inflow, pulmonary venous
      flow, and other standard echocardiographic measurements. RESULTS: No differences
      in peak myocardial early velocity (Em), deceleration time of Em, and myocardial
      isovolumic relaxation time measured from mitral lateral annulus before, 24 hours
      after, and one month after ECV were found. Peak myocardial late velocity measured
      24 hours after ECV increased significantly at the end of 1 month. CONCLUSION:
      There were not any changes in LV diastolic function except restoration of atrial
      mechanical contraction following ECV in patients with persistent AF.

PMID- 17214621
TI  - Reliability of echocardiographic indices of dyssynchrony.
AB  - BACKGROUND: Echocardiographic indices of dyssynchrony are increasingly used to
      select candidates for cardiac resynchronization therapy. For widespread screening
      of heart failure patients, such variables need to be comparable when evaluated by
      different operators using different equipment. OBJECTIVE AND METHODS: To evaluate
      the reproducibility and obtainability of echocardiographic indices of mechanical
      dyssynchrony, we studied 40 subjects stratified according to QRS morphology and
      systolic function. Two echocardiograms were performed on each patient by
      different sonographers on different machines and each study was analyzed by two
      observers. RESULTS: All blood-pool and tissue Doppler indices of dyssynchrony
      were obtainable in over 97% of cases. Blood-pool Doppler measures were the most
      reproducible indices of intraventricular dyssynchrony (aortic ejection delay) and
      interventricular dyssynchrony (aortopulmonary difference in ejection delay). For
      annular tissue Doppler delays, the time to peak velocity was consistently more
      reproducible than the time to velocity onset. CONCLUSION: Differences in the
      reliability of echocardiographic indices may affect their suitability as
      screening tests for dyssynchrony.

PMID- 17214622
TI  - Low-level exercise echocardiography fails to elicit left ventricular contractile
      reserve in patients with aortic stenosis, reduced ejection fraction, and low
      transvalvular gradient.
AB  - BACKGROUND: Low-level exercise echocardiography is useful to assess left
      ventricular (LV) contractile reserve after an acute myocardial infarction.
      Whether low-level exercise can elicit LV contractile reserve in patients with
      severe aortic stenosis, reduced LV systolic function and low transvalvular
      gradient are unknown. Accordingly, the value of low-level exercise to elicit
      contractile reserve was assessed in these patients using dobutamine
      administration as the gold standard method. METHODS AND RESULTS: Seventeen
      patients with severely decreased aortic valve area (0.75 +/- 0.03 cm(2)), reduced
      LV ejection fraction (35 +/- 2%) and low mean transvalvular gradient (23 +/- 3
      mmHg) underwent low-level exercise and dobutamine echocardiography. Ejection
      fraction increased by 23% (P < 0.001) with dobutamine and decreased by 8% (P =
      0.2) with low-level exercise. Left ventricular outflow tract velocity time
      integral increased from 13 +/- 1 to 16.7 +/- 1 cm (P < 0.001) with dobutamine but
      did not change with low-level exercise (13 +/- 1 vs. 13.5 +/- 1, P = 0.5).
      CONCLUSION: Low-level exercise fails to elicit LV contractile reserve in patients
      with severe aortic stenosis, reduced LV systolic function, and low transvalvular
      gradient.

PMID- 17214624
TI  - Myocardial tissue velocities in neonates.
AB  - BACKGROUND: Tissue Doppler echocardiography (TDE) has been applied to the
      children age group; however, myocardial tissue velocities of neonates have been
      reported by few researchers. METHODS: Myocardial velocities along the
      longitudinal axis of the left ventricle were measured in two groups: 50 term
      neonates within 5 days after birth and 54 healthy children by TDE. Sample volumes
      were placed in mitral lateral annulus (MLA), mitral medial annulus (MMA), and in
      the basal and middle parts of the left ventricular lateral wall (LVLW) and
      interventricular septum (IVS). RESULTS: The highest myocardial velocities were
      obtained from MLA. In all segments, the mean systolic velocity (Sw) was found
      significantly lower than the mean early diastolic (Ew) and atrial systolic
      velocities (Aw) (P < 0.0001). The mean Aw was the dominant component in the MMA
      and were significantly higher than Ew (P < 0.001). The mean Ew/Aw in the MMA and
      MLA increased significantly while replacing the Doppler beam from base to apex.
      TDE indexes of neonates, except Aw obtained from MLA and MMA, were significantly
      lower than that of children group (P < 0.0001 and P < 0.0001, respectively). The
      mean E/Ew ratio of the left ventricle in neonates was found to be significantly
      higher than that found in children group (P < 0.0001). CONCLUSION: In neonates,
      the diastolic and systolic myocardial velocities of the left ventricle were
      significantly lower than those measured in the children group. Decreased
      myocardial tissue values of neonates might be reflecting the immaturity of
      neonatal myocardium.

PMID- 17214623
TI  - Ultrasonic integrated backscatter discloses intramyocardial hemorrhage in
      patients with acute myocardial infarction.
AB  - BACKGROUND: It has been reported that intramyocardial hemorrhage (IH) can be
      detected by magnetic resonance imaging (MRI) and IH correlates with the poor
      prognosis of acute myocardial infarction (AMI). We examined whether integrated
      backscatter (IBS) can disclose IH in patients with AMI. We recorded IBS images in
      34 patients with AMI who underwent coronary angioplasty within 12 hours of
      symptom onset. METHODS: We measured calibrated IBS (C-IB) and cyclic variation
      (CV) in the center of the risk area on the third day after reperfusion. C-IB was
      calculated as: average IBS value of risk area--average IBS value of
      intraventricular blood. MRI was performed within 3 days after reperfusion.
      Regional wall motion score index (RWMSI) was calculated as follows: sum of scores
      (0 - 4) in risk area/number of segments of risk area. We evaluated left
      ventricular function using RWMSI shortly and one month after reperfusion.
      RESULTS: RWMSI in the IH group (12 cases) was significantly higher than in the
      non-IH group (2.3+/-0.5 vs. 1.8+/-0.6: P<0.01) one month later, while RWMSI in
      both groups was almost the same shortly after reperfusion. The IH group showed a
      significantly higher value of C-IB than the non-IH group (18.6+/-2.0 vs. 16.0+/
      1.4: P<0.01), while there were no significant differences in CV values between
      two groups. Using 17 as a cutoff value of C-IB, C-IB can detect IH with 92%
      sensitivity and 91% specificity. Using both CV and C-IB, however, IH can be
      detected more specifically. CONCLUSION: Ultrasonic IBS, especially C-IB,
      discloses intramyocardial hemorrhage in patients with reperfused AMI.

PMID- 17214625
TI  - Patchy myocardial fibrosis 20 years after radiation therapy.
AB  - We describe a case of a young woman diagnosed with Ewings sarcoma at age 8 and
      treated with adriamycin and radiation therapy. Twenty years later the patient has
      a cardiomyopathy and a focal area of patchy infiltration of fibrotic tissue along
      the left ventricle and atrium. Although fibrosis due to radiation exposure has
      been demonstrated on biopsy and autopsy studies, we are not aware of previous
      reports of echocardiographic demonstration of this finding. The most likely
      explanation for the fibrosis location is the left posterolateral direction of the
      radiation beam.

PMID- 17214626
TI  - Large unrepaired aortopulmonary window--survival into the seventh decade.
AB  - Aortopulmonary (AP) window is a rare cardiac malformation. We report a patient
      with Eisenmenger syndrome secondary to a large unrepaired AP window who gave
      birth to three children in her thirties, survived into her fifties with
      relatively preserved quality of life, and died at age 60.

PMID- 17214627
TI  - Assessment of surgically unroofed coronary sinus by live/real time three
      dimensional transthoracic echocardiography.
AB  - Both two-dimensional transthoracic echocardiography (2DTTE) and live/real time
      three-dimensional transthoracic echocardiography (3DTTE) were attempted in a 25
      year-old morbidly obese female with total anomalous pulmonary venous return
      (TAPVR) into the coronary sinus (CS) in whom surgical unroofing of CS with patch
      closure of CS ostium was performed in infancy to redirect pulmonary venous flow
      into the left atrium (LA). The patient had become increasingly symptomatic over
      the past 1 year because of severe left-to-right shunting due to dehiscence of the
      patch used to close the CS ostium. Despite a poor acoustic window, 3DTTE was able
      to identify a communication between the LA and CS which resulted from surgical
      unroofing of the CS as well as flow signals moving into the right atrium from the
      CS. These findings were not detected by 2DTTE.

PMID- 17214628
TI  - Unusual superior vena cava thrombus (partly obstructive) extending through right
      atrium to eustachian valve.
AB  - A 50-year-old patient with end-stage renal disease who was being dialyzed with an
      internal jugular catheter presented with fever. Transthoracic and transesophageal
      echo demonstrated a thrombus in the inferior vena cava, protruding into the right
      atrium and extending to the eustachian valve to which it was adherent. Multiple
      organisms grew from the blood as well as the catheter tip. Antibiotic therapy was
      started with Vancomycin and Gentamicin but later changed to other combinations
      according to sensitivity studies. Coumadin was also given.

PMID- 17214629
TI  - Posttraumatic pulmonary arteriovenous fistula presenting as multiple embolic
      strokes.

PMID- 17214630
TI  - Echocardiographic evaluation of ventricular function in mice.
AB  - Ventricular dysfunction remains a hallmark of most cardiac disease. The mouse has
      become an essential model system for cardiovascular biology, and echocardiography
      an established tool in the study of normal and genetically altered mice. This
      review describes the measurement of ventricular function, most often left
      ventricular function, by echocardiographic methods in mice. Technical limitations
      related to the small size and rapid heart rate in the mouse initially argued for
      the performance of echocardiography under anesthesia. More recently, higher frame
      rates and smaller probes operating at higher frequencies have facilitated imaging
      of conscious mice in some, but not all, experimental protocols and conditions.
      Ventricular function may be qualitatively and quantitatively evaluated under both
      conditions. Particular detail is provided for measurement under conscious
      conditions, and measurement under conscious and sedated or anesthestized
      conditions are contrasted. Normal values for echocardiographic indices for the
      common C57BL/6 strain are provided. Diastolic dysfunction is a critical
      pathophysiologic component of many disease states, and progress in the
      echocardiographic evaluation of diastolic function is discussed. Finally,
      echocardiography exists among several competing imaging technologies, and these
      alternatives are compared.

PMID- 17214631
TI  - Infarct size assessment in mice.
AB  - Genetically modified mice are used extensively in models of ischemia reperfusion
      (I/R) and nonreperfused myocardial infarction (MI) to gain insights into pathways
      involved in these pathologies. Echocardiography is an ideal noninvasive tool to
      serially monitor the cardiac murine phenotype. The present review details the
      surgical aspects of I/R and MI models and the measurement of MI size by pathology
      techniques and the input of echocardiographic techniques including the extent of
      wall motion abnormality and of perfusion defects using myocardial contrast
      echocardiography in the assessment of murine area at risk and MI size.

PMID- 17214632
TI  - Doppler ultrasound in mice.
AB  - Color, power, spectral, and tissue Doppler have been applied to mice. Due to the
      noninvasive nature of the technique, serial intraindividual Doppler measurements
      of cardiovascular function are feasible in wild-type and genetically altered mice
      before and after microsurgical procedures or to follow age-related changes. Fifty
      megahertz ultrasound biomicroscopy allows to record the first beats of the
      embryonic mouse heart at somite stage 5, and the first Doppler-flow signals can
      be recorded after the onset of intrauterine cardiovascular function at somite
      stage 7. Using 10- to 20-MHz ultrasound transducers in the mouse embryo, cardiac,
      and circulatory function can be studied as early as 7.5 days after postcoital
      mucous plug. Postnatal Doppler ultrasound examinations in mice are possible from
      birth to senescent age. Several strain-, age-, and gender-related differences of
      Doppler ultrasound findings have been reported in mice. Results of Doppler
      examinations are influenced by the experimental settings as stress testing or
      different forms of anesthesia. This review summarizes the present status of
      Doppler ultrasound examinations in mice and animal handling in the framework of a
      comprehensive phenotype characterization of cardiac contractile and circulatory
      function.

PMID- 17214633
TI  - Regulation of calprotectin expression by interleukin-1alpha and transforming
      growth factor-beta in human gingival keratinocytes.
AB  - BACKGROUND AND OBJECTIVE: Calprotectin, a heterodimer of S100A8 and S100A9 with
      antimicrobial properties, is expressed in gingival keratinocytes and plays an
      important role in innate immunity. Because calprotectin expression is localized
      in the spinous cell layer of the gingival epithelium, we hypothesized that the
      expression of calprotectin in keratinocytes is related to the differentiation
      stage. The aim of the present study was to investigate the relationship between
      calprotectin expression and keratinocyte differentiation using some factors that
      regulated its differentiation. MATERIAL AND METHODS: Normal human gingival
      keratinocytes were isolated from gingival tissues obtained at the extraction of
      wisdom teeth, and were cultured in serum-free keratinocyte medium supplemented
      with interleukin-1alpha or calcium, which promote keratinocyte differentiation,
      and transforming frowth factor-beta (TGF-beta) or retinoic acid, which suppress
      its differentiation. The expression of S100A8/A9 mRNA and the production of
      calprotectin in normal human gingival keratinocytes were examined by northern
      blotting and enzyme-linked immunosorbent assay, respectively. The expression of
      cytokeratin 14, involucrin and filaggrin (marker proteins of keratinocyte
      differentiation) was investigated by immunohistochemical staining, and the DNA
      binding activity of CCAAT/enhancer binding protein alpha (C/EBPalpha), a
      transcription factor, was examined by electrophoretic mobility shift assay.
      RESULTS: The expression of S100A8/A9 mRNA and the production of calprotectin were
      increased by interleukin-1alpha and calcium, but decreased by TGF-beta. RA
      inhibited the expression of S100A8/A9 and keratinocyte differentiation, which
      were induced by interleukin-1alpha. C/EBPalpha DNA-binding activity in normal
      human gingival keratinocytes was enhanced by interleukin-1alpha and calcium, but
      suppressed by TGF-beta. CONCLUSION: The present study suggests that calprotectin
      expression is related to keratinocyte differentiation and that C/EBPalpha is a
      regulator of calprotectin expression in keratinocytes.

PMID- 17214634
TI  - Aging stimulates cyclooxygenase-2 expression and prostaglandin E2 production in
      human periodontal ligament cells after the application of compressive force.
AB  - BACKGROUND AND OBJECTIVES: Some clinical studies show that alveolar crestal bone
      loss is higher in adults than in young patients during orthodontic treatment, but
      the causes of such a phenomenon have not been elucidated. It is known that
      prostaglandin E2 (PGE2) is a proinflammatory agent and one of the potent
      osteoclast-inducing factors, and is produced by human periodontal ligament cells
      in response to orthodontic force. The aim of this study was to investigate age
      related change in the biosynthetic capacity of PGE2 and its regulatory gene,
      cyclooxygenase 2 (COX-2) from periodontal ligament cells in response to
      mechanical stress. METHODS: Compressive force of 2 g/cm2 was applied for 3-48 h
      to periodontal ligament cells obtained from human donors aged 9-50 years, and COX
      2 mRNA expression in and PGE2 production by the periodontal ligament cells in
      response to the compressive force were examined. RESULTS: Application of a
      compressive force of 2 g/cm2 for 3-48 h significantly stimulated these factors in
      both time- and age-dependent manners. Furthermore, these increases were
      dramatically larger in periodontal ligament cells obtained from donors over the
      age of 35. CONCLUSIONS: Periodontal ligament cells obtained from old donors have
      significantly greater COX-2 expression and PGE2 production in response to
      compressive force than those from younger donors. The turning point of aging,
      where significantly larger amounts of theses factors begin production, appears to
      be around the age of 35. These results may be positively related to the
      acceleration of alveolar crestal bone loss during orthodontic treatment in adult
      patients.

PMID- 17214635
TI  - Identification of genes related to mechanical stress in human periodontal
      ligament cells using microarray analysis.
AB  - BACKGROUND AND OBJECTIVE: Differential expression of genes in human periodontal
      ligament (PDL) under mechanical stress, such as orthodontic force, is thought to
      be involved in the remodeling of PDL cells and periodontal tissues. However,
      little is known about the genes expressed in PDL cells under mechanical stress.
      MATERIAL AND METHODS: We employed microarray analysis to assess, in a
      comprehensive manner, the gene expression profiles in PDL cells compressed by a
      static force using an in vitro three-dimensional culture system. Six genes were
      selected and validated by quantitative real-time polymerase chain reaction
      analysis, consistent with the microarray data. RESULTS: The microarray data
      revealed that 108 of 30,000 genes tested were differentially expressed by
      mechanical force loading. Among them, 85 genes were up-regulated by mechanical
      stress, while 23 genes were down-regulated, judging by the thresholds of a two
      fold increase/decrease compared with the controls. Thirty-two of the up-regulated
      and eight of the down-regulated genes, well-characterized in protein function,
      were involved in numerous biological processes including cell communication, cell
      signaling, cell cycle, stress response, and calcium release. However, several
      genes differentially expressed in our microarray data have not been well defined
      as stress-response molecules. CONCLUSION: Our microarray is the first to show the
      gene profile in PDL cells caused by mechanical stress; however, further studies
      to clarify the physiological function of these molecules in PDL cells are
      required.

PMID- 17214636
TI  - The IL1A (-889) gene polymorphism is associated with chronic periodontal disease
      in a sample of Brazilian individuals.
AB  - BACKGROUND AND OBJECTIVE: It has been proposed that genotypes reflective of
      polymorphisms in cytokine genes can predispose individuals to disease by
      enhancing inflammatory processes. The C/T polymorphism at position -889 of the
      IL1A gene influences interleukin-1alpha expression, with the T allele inducing
      higher expression. The aim of this study was to evaluate the association of the
      IL1A (-889) gene polymorphism in Brazilian individuals with different clinical
      forms of periodontitis and severity of disease. MATERIAL AND METHODS: DNA was
      obtained from oral swabs of 163 Brazilian individuals and was amplified using the
      polymerase chain reaction (PCR). Products were submitted to digestion and were
      analyzed by electrophoresis to distinguish the C and T alleles. RESULTS: A
      significant difference in the genotype distribution was observed when comparing
      the chronic periodontitis group with the control group, evaluating only
      nonsmokers (chi-squared analysis = 9.91; p = 0.007), as well as when smokers were
      included (chi-squared analysis = 6.36; p = 0.04). Moreover, we observed a higher
      incidence of the T allele in the chronic periodontitis group (37.8%) when
      compared with the control group (18.4%) in nonsmokers (p = 0.006, odds ratio =
      2.69, confidence interval = 1.27-5.68) and also when smokers were included (p =
      0.03, odds ratio = 1.87, confidence interval = 0.98-3.56). No statistical
      difference was observed when the aggressive periodontitis group was compared with
      the control group. With regard to severity of disease, no statistical difference
      was observed. CONCLUSION: These data show an association of the IL1A (-889)
      polymorphism with chronic periodontitis in Brazilian individuals.

PMID- 17214637
TI  - High glucose-boosted inflammatory responses to lipopolysaccharide are suppressed
      by statin.
AB  - BACKGROUND AND OBJECTIVE: It has been established that periodontal diseases are
      more prevalent and of greater severity in diabetic patients than in nondiabetic
      patients. Recent studies have underscored the role of monocytes and macrophages
      in periodontal tissue inflammation and destruction in diabetic patients. Although
      it has been shown that monocytes isolated from diabetic patients produce more
      inflammatory cytokines and that gingival crevicular fluid collected from diabetic
      patients contains higher levels of inflammatory cytokines than that obtained from
      nondiabetic patients, the underlying mechanisms are not well understood. MATERIAL
      AND METHODS: U937 histiocytes cultured in medium containing either normal (5 mM)
      or high (25 mM) glucose were treated with 100 ng/ml of lipopolysaccharide for
      24h. After the treatment, cytokines in the medium and cytokine mRNA in the cells
      were quantified using enzyme-linked immunosorbet assay and real-time polymerase
      chain reaction, respectively. RESULTS: In this study, we demonstrated that the
      pre-exposure of U937 histiocytes to high glucose concentrations markedly
      increased the lipopolysaccharide-induced secretion of pro-inflammatory cytokines
      and chemokines and the cellular inducible nitric oxide level compared with pre
      exposure to normal glucose. Our data also showed that the increased secretion of
      cytokines was a result of increased mRNA expression. Furthermore, the effects of
      statin and peroxisome proliferators-activated receptor agonists on high glucose
      enhanced secretion of cytokines were determined. The results showed that
      simvastatin, but not fenofibrate or pioglitazone, inhibited high glucose-enhanced
      cytokine release. CONCLUSION: This study has shown that high glucose
      concentrations and lipopolysaccharide act synergistically to stimulate the
      secretion of inflammatory mediators, and that statin is capable of suppressing
      the high glucose-boosted proinflammatory response. This study therefore
      delineates a novel mechanism by which hyperglycemia enhances the inflammatory
      responses of macrophages and suggests that statin may be useful in the treatment
      of periodontal disease in diabetic patients.

PMID- 17214638
TI  - The up-regulation of type I plasminogen activator inhibitor in human gingival
      fibroblasts stimulated with cyclosporin A.
AB  - BACKGROUND AND OBJECTIVE: Cyclosporin A is used as an immunosuppressive agent and
      its prominent side-effect is the induction of fibrous gingival overgrowth. The
      progression of fibrous gingival overgrowth results from the accumulation of
      extracellular matrix. Type I plasminogen activator inhibitor (PAI-1) acts as the
      inhibitor of extracellular matrix degradation and is involved in some fibrotic
      diseases. However, little is known about the correlation between PAI-1 and
      cyclosporin A-induced gingival overgrowth. The aim of this study was to
      investigate the effects of cyclosporin A on the expression of PAI-1 mRNA and
      protein in human gingival fibroblasts human gingival fibroblasts in vitro and to
      compare PAI-1 expression in normal healthy gingival tissues and cyclosporin A
      induced gingival overgrowth specimens in vivo. MATERIAL AND METHODS: Quantitative
      reverse transcription-polymerase chain reaction and western blot assay were used
      to investigate the effects on human gingival fibroblasts exposed to cyclosporin
      A. In addition, 10 cyclosporin A-induced gingival overgrowth specimens and five
      normal gingival tissues were examined by immunohistochemistry. RESULTS:
      Investigations of the time dependence of PAI-1 mRNA expression in human gingival
      fibroblasts treated with 200 ng/ml of cyclosporin A revealed a rapid accumulation
      of the transcript: a significant signal was first detectable after 1 h of
      exposure and the signal remained elevated throughout the 24-h incubation period
      (p < 0.05). Cyclosporin A was also found to up-regulate PAI-1 protein in a time
      dependent manner (p < 0.05). The PAI-1 staining in gingival tissue was stronger
      in the cyclosporin A-induced gingival overgrowth group than in the normal
      gingival group (p < 0.05). In the cyclosporin A-induced gingival overgrowth
      group, intensive staining for PAI-1 expression was observed mainly in the
      cytoplasm of fibroblasts, endothelial cells and inflammatory cells. CONCLUSION:
      These findings suggest that the up-regulation of PAI-1 may play an important part
      in the molecular pathogenesis of cyclosporin A-induced gingival overgrowth.

PMID- 17214639
TI  - Lead exposure and periodontitis in US adults.
AB  - BACKGROUND AND OBJECTIVE: Lead is known to have significant effects on bone
      metabolism and the immune system. This study tested the hypothesis that lead
      exposure affects periodontitis in adults. MATERIAL AND METHODS: This study used
      the data from the Third National Health and Nutrition Examination Survey (NHANES
      III, 1988-94). It analyzed data from 2500 men and 2399 women, 20-56 yr old, who
      received complete periodontal examination. Periodontitis was defined as the
      presence of > 20% of mesial sites with >or= 4 mm of attachment loss. Lead
      exposure was grouped into three categories: < 3; 3-7; and > 7 microg/dL.
      Covariates were cotinine levels, poverty ratio, race/ethnicity, education, bone
      mineral density, diabetes, calcium intake, dental visit, and menopause (for
      women). All analyses were performed separately for men and women and considering
      the effect design. Univariate, bivariate, and stratified analysis was followed by
      multivariable analysis by estimating prevalence ratios through poisson
      regression. RESULTS: After adjustment for confounders, the prevalence ratios,
      comparing those with a lead blood level of > 7 microg/dL to those with a lead
      blood level of < 3 microg/dL was 1.70 (95% confidence interval (CI): 1.02, 2.85)
      for men and 3.80 (95% CI: 1.66, 8.73) for women. CONCLUSION: The lead blood level
      was positively and statistically associated with periodontitis for both men and
      women. Considering the public health importance of periodontitis and lead
      exposure, further studies are necessary to confirm this association.

PMID- 17214641
TI  - Differential chemokine response of fibroblast subtypes to complement C1q.
AB  - BACKGROUND AND OBJECTIVE: The pathogenesis of periodontitis includes an
      inappropriate activation of the classical complement cascade (C') with
      accumulation of inflammatory C' products in fluids and tissues. Our hypothesis is
      that in vivo the C' product, C1q, may act as a regulatory component of the innate
      immune response of distinct matrix fibroblasts to the inflammatory environment.
      This study analyzed the C1q induction of pro-inflammatory cytokine secretion in
      fibroblast subtypes derived from distinct periodontal tissues, and identified a
      mechanism of the cell response. MATERIAL AND METHODS: Primary human gingival
      fibroblast, periodontal ligament fibroblast, and granulation tissue fibroblast
      cultures were treated for 24 h with C1q. Protein arrays assessed the secretory
      profile of constitutive and C1q-inducible pro-inflammatory cytokines, and enzyme
      linked immunosorbent assays were used to quantify the kinetics of each inducible
      cytokine. RESULTS: Granulation tissue fibroblast cultures were unresponsive to
      C1q challenge. In contrast, periodontal ligament fibroblasts responded with a
      release of monocyte chemoattractant protein (MCP)-1, interleukin-6, interleukin
      8, and macrophage inflammatory protein (MIP)-1beta higher than the basal level by
      8.2-, 7.0-, 3.8-, and 7.2-fold, respectively. Human gingival fibroblast cultures
      increased secretion of these chemokines by 5.2-, 4.5-, 3.0-, and 9.8-fold,
      respectively. Inhibitor studies revealed that C1q-inducible release of chemokines
      by the human gingival fibroblast and periodontal ligament cultures was contingent
      upon p38 mitogen-activated protein kinase activity. CONCLUSION: The ability of
      C1q to stimulate secretion of pro-inflammatory chemokines depends upon which
      specific fibroblast subtype is involved. Targeting C1q-activated intracellular
      signaling pathways may be an effective means to inhibit the production of
      chemokines that promote inflammatory cell infiltration into gingival and
      periodontal ligament tissues.

PMID- 17214640
TI  - Roxithromycin inhibits tumor necrosis factor-alpha-induced matrix
      metalloproteinase-1 expression through regulating mitogen-activated protein
      kinase phosphorylation and Ets-1 expression.
AB  - BACKGROUND AND OBJECTIVE: In periodontitis, matrix metalloproteinases (MMPs) are
      upregulated in response to locally released inflammatory cytokines, resulting in
      pathologic processes. Roxithromycin is a 14-membered ring macrolide antibiotic
      with broad-spectrum antibacterial effects against oral pathogens and
      immunomodulatory effects. Recently, we reported that roxithromycin inhibits tumor
      necrosis factor (TNF)-alpha-induced vascular endothelial growth factor expression
      in human periodontal ligament (HPDL) cell cultures. In the present study, we
      examined the effect of roxithromycin on TNF-alpha-induced MMP-1 production by
      HPDL cells. MATERIAL AND METHODS: Cultured cells were incubated with 1% fetal
      bovine serum for 24 h, followed by treatment with 10 ng/ml TNF-alpha, 10 microM
      roxithromycin, and mitogen-activated protein kinase inhibitor at various
      concentrations. Culture supernatants and sediments were collected at different
      time-points and used for enzyme-linked immunosorbent assays, and northern and
      western blot analyses. RESULTS: In HPDL cell cultures, roxithromycin strongly
      inhibited TNF-alpha-induced MMP-1 mRNA expression and production. The inhibition
      of MMP-1 gene expression by roxithromycin was dependent on de novo protein
      synthesis and was regulated at the transcriptional level. Roxithromycin
      significantly inhibited TNF-alpha-induced c-Jun N-terminal kinase activation
      (JNP) and marginally inhibited extracellular signal-regulated kinase (ERK) 1/2
      activation, but not p38 mitogen-activated protein kinase activation. Furthermore,
      roxithromycin reduced the induction of Ets-1, one of the critical factors in MMP
      1 transcription. CONCLUSION: Roxithromycin inhibits TNF-alpha-mediated MMP-1
      induction through the downregulation of ERK1/2 and JNK activation and the
      subsequent reduction of Ets-1, suggesting that roxithromycin may have therapeutic
      use in periodontitis and other chronic inflammatory conditions involving MMP-1
      induction.

PMID- 17214642
TI  - Areca nut extracts reduce the intracellular reactive oxygen species and release
      of myeloperoxidase by human polymorphonuclear leukocytes.
AB  - BACKGROUND AND OBJECTIVE: Polymorphonuclear leukocytes (PMN) represent the first
      line of host defense. Areca nut extract inhibits the bactericidal activity of,
      and the release of superoxide anion (O2- ) by, PMN. This study investigated the
      effects of areca nut extract on the intracellular production of reactive oxygen
      species (ROS) and on the extracellular release of lysosomal enzyme,
      myeloperoxidase (MPO), by PMN. The effects of arecoline, a principal component of
      areca nut, were also examined. MATERIAL AND METHODS: Human PMN were treated with
      various concentrations of areca nut extract or arecoline followed by treatment
      with Hanks' balanced salt solution, with or without cytochalasin B and fMet-Leu
      Phe (CB/fMLP). The viability of PMN was determined using propidium iodide
      staining and flow cytometry. The presence of intracellular ROS was determined
      using 2',7'-dichlorofluorescin diacetate and fluorometry. MPO release was
      determined using a substrate assay. RESULTS: Areca nut extract (25 and 50
      microg/ml) significantly decreased the viability of PMN. The intracellular levels
      of ROS and the extracellular release of MPO were induced in PMN by CB/fMLP.
      Exposure of PMN to areca nut extract (up to 25 microg/ml) or to arecoline (up to
      2 mg/ml) did not directly affect the levels of ROS and MPO activity. However,
      under conditions that did not affect the viability of PMN, the ability of CB/fMLP
      to trigger production of intracellular ROS and release of MPO in human PMN was
      significantly suppressed by areca nut extract and arecoline. CONCLUSION: Areca
      nut impaired the activation of PMN by CB/fMLP that might decrease the
      effectiveness of PMN in the host defense. Alternatively, exposure of PMN to areca
      nut extract could decrease the capacity of PMN to damage tissues.

PMID- 17214643
TI  - Heterogeneity in the collagen-degrading ability of Porphyromonas gingivalis
      stimulated human gingival fibroblasts.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to characterize the
      heterogeneity of the collagen-degrading ability of different human gingival
      fibroblast cell lines treated with Porphyromonas gingivalis supernatant. MATERIAL
      AND METHODS: Seven human gingival fibroblast cell lines were analyzed for their
      ability to cleave Type I collagen in the presence and absence of culture
      supernatant from P. gingivalis ATCC 33277 (10% v/v). The matrix
      metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) produced by these
      human gingival fibroblasts were monitored at the protein level by zymography
      and/or western blot analyses, as well as at the mRNA level by reverse
      transcription-polymerase chain reaction. RESULTS: The collagen-degrading ability
      of the human gingival fibroblasts increased in four cell lines (aggressive) and
      was only slightly altered in the other three cell lines (nonaggressive) in the
      presence of P. gingivalis supernatant. MMP-1, MMP-2, and MMP-3 more readily
      underwent activation while the TIMP-1 level was decreased in the conditioned
      media from a P. gingivalis-treated human gingival fibroblast aggressive cell
      line. None of these was altered in a nonaggressive cell line. The mRNA levels of
      the MMPs and TIMPs were only slightly different between these two cell lines.
      CONCLUSION: Heterogeneity exists in human gingival fibroblasts in regard to their
      collagenolytic activity in the presence of P. gingivalis.

PMID- 17214644
TI  - Milk basic protein increases alveolar bone formation in rat experimental
      periodontitis.
AB  - BACKGROUND AND OBJECTIVE: It is conceivable that the active components extracted
      from milk whey protein (i.e. milk basic protein, MBP) stimulate bone formation
      and suppress bone resorption. Periodontitis is characterized by excessive
      alveolar bone resorption. We examined whether milk basic protein could recover
      alveolar bone loss in rat experimental periodontitis. MATERIAL AND METHODS: A
      nylon ligature was placed around the cervix of molars in 8-wk-old male Fischer
      rats for 20 d. Then, the ligature was removed and a powder diet containing 0.2 or
      1.0% milk basic protein was provided daily for another 45-90 d. On days 45 and
      90, the maxillae were extracted and analyzed using microcomputerized tomography
      (micro-CT), followed by histological analysis. RESULTS: Micro-CT images showed
      that alveolar bone resorption was severely induced around the molar by the 20-d
      ligature procedure. Treatment with high-dose milk basic protein (1.0%) clearly
      recovered ligature-induced alveolar bone resorption on days 45 and 90, whereas
      low-dose milk basic protein (0.2%) did not show such a clear effect. Histological
      examination clarified that the osteoid thickness of alveolar bone was dose
      dependently increased by milk basic protein treatment for 90 d. CONCLUSION: These
      findings suggest that a systemic administration of milk basic protein may be
      effective for the recovery of alveolar bone loss in periodontitis.

PMID- 17214647
TI  - Trauma, policy, and public health on the U.S.-Mexico border.

PMID- 17214645
TI  - A comparison of root surface instrumentation using two piezoelectric ultrasonic
      scalers and a hand scaler in vivo.
AB  - BACKGROUND AND OBJECTIVE: This study compared the effectiveness of two
      piezoelectric ultrasonic scalers and a hand scaler for subgingival scaling and
      root planing in vivo. MATERIAL AND METHODS: Fifteen patients with advanced
      periodontal disease and with teeth scheduled for extraction were selected for
      this study. Three experimental groups of 10 teeth each were treated with one of
      two piezoelectric ultrasonic scalers [Vector scaler and Enac scaler] or with a
      hand scaler. Instrumentation was continued until the root surface felt hard and
      smooth to an explorer tip. The root surface characteristics after instrumentation
      were examined using scanning electron microscopy, and the amount of remaining
      calculus, roughness and loss of tooth substance were estimated using the
      remaining calculus index and roughness loss of tooth substance index. RESULTS:
      The remaining calculus index did not differ significantly among the three groups.
      The roughness loss of tooth substance index was significantly lower for the
      Vector scaler and Enac scaler groups than for the hand scaler group and also
      differed significantly between the Vector scaler and Enac scaler groups.
      CONCLUSION: This study suggests that the Vector scaler produces a smooth root
      surface with minimal loss of tooth substance. It is a reasonable choice for
      gentle periodontal maintenance treatment.

PMID- 17214648
TI  - Congregational health ministries: a national study of pastors' views.
AB  - OBJECTIVES: Since the 1980s, there has been a growing, but little studied,
      movement that organizes church-based health services under the direction of a
      coordinator, usually a registered nurse. These Congregational Health Ministries
      (CHMs) emphasize health promotion and disease prevention. We compared the
      perceptions of pastors with and without organized CHMs and the characteristics of
      their congregations' health ministries. DESIGN: We used a quantitative, cross
      sectional survey design. SAMPLE: We surveyed a national multidenominational
      sample of 349 pastors representing over 80 Christian denominations. RESULTS: With
      limited resources, CHMs provide significant health promotion, disease prevention,
      and support services. Pastors with CHMs were significantly more involved in
      health promotion and disease prevention activities. Pastors without CHMs
      perceived a need for congregations to be involved in health-related services and
      were willing to become involved if they have adequate resources. CONCLUSIONS:
      Because of long-term trusting relationships that exist between congregants and
      those who minister to them, religious congregations may be ideally suited to
      provide cost-effective, community-based health promotion and disease prevention
      services as well as health-supporting services to community-dwelling elderly and
      persons with chronic illnesses.

PMID- 17214650
TI  - The Measles Initiative to control measles in Kenya.
AB  - PURPOSE: To describe the epidemiology of measles in Kenya and evaluate the
      Measles Initiative's (MI's) mass immunization campaign and its impact on measles
      control in Kenya. METHODS: This descriptive study focused on evaluating the MI's
      simultaneous mass campaigns in the provinces of Kenya, the implementation process
      of the campaign strategy, post-campaign impact data, and pre-campaign measles
      trends. Secondary data were obtained from the Kenya Ministry of Health and MI
      documentation involving vaccine coverage, and morbidity and mortality rates.
      Analysis focused on program achievement with a comparison of immunization
      coverage results and program goals. OUTCOMES: Campaign goals of vaccination
      coverage were successfully achieved, and subsequent surveillance data indicate
      significant decreases in measles morbidity and mortality. Barriers to
      participation, sociocultural factors, and environmental demographics were
      identified and addressed. IMPLICATIONS: The success of the MI immunization
      program was the result of the commitment of expert international public health
      agencies in partnership with the Kenyan government. The strategies used for this
      successful public health activity can be applied to improve vaccination programs
      in other countries.

PMID- 17214649
TI  - Health beliefs of Haitian elders related to influenza prevention.
AB  - OBJECTIVE: Each year, about 20% of the persons living in the United States gets
      influenza, and the majority of those who die as a consequence are over 65. Many
      of these deaths may be preventable. In this study, the health beliefs, attitudes,
      and cultural practices related to the prevention of influenza by Haitian elders
      are studied. DESIGN AND SAMPLE: Using a focused ethnographic approach, 10 adults
      above the age of 55 and born in Haiti were interviewed. METHODS: Data were
      collected using interviews and participant observation. Interviews were conducted
      in Creole by the primary author. Participant observation occurred for the length
      of a "flu season" in a neighborhood nurse-managed clinic during the provision of
      routine health care. RESULTS: Themes of competing paradigms, fear of sickness,
      taking care of oneself, and cautious willingness emerged. CONCLUSIONS: The
      participants described what is known in western medicine as influenza, as "a
      cold," or "a big cold." While they were uncertain of influenza immunizations,
      there was an overwhelming willingness to accept one if recommended by respected
      others and trusted health providers. The results of the study can serve as a
      springboard for future attempts to better understand this unique and at-risk
      population.

PMID- 17214651
TI  - A targeted testing program for tuberculosis control and prevention among
      Baltimore city's homeless population.
AB  - OBJECTIVE: To identify cases of latent tuberculosis infection (LTBI) and improve
      access to TB treatment among the inner-city homeless. DESIGN: This is an
      intervention study describing the impact of a public health program on TB
      prevention and control. SAMPLE: The target population for the project was
      residents and recent graduates of a residential addictions recovery program in a
      faith-based, inner-city mission. INTERVENTION: Faculty and student nurses
      administered purified protein derivative (PPD) tuberculin skin tests and TB
      symptom assessments on site to homeless Mission residents. Residents testing
      positive for TB infection were referred to the local city health department for
      follow-up. Residents placed on prophylactic therapy received intensive tracking
      and coaching interventions to encourage adherence to the 9-month regimen.
      RESULTS: Ninety-eight percent of the target population was screened for LTBI.
      Ninety percent of residents requiring treatment for LTBI successfully accessed
      treatment services. Thirty-three percent of residents completed at least 6 months
      of treatment. CONCLUSION: The program demonstrated a modest improvement in
      treatment completion among the inner-city homeless when compared with local City
      Health Department treatment completion rates. This program demonstrates how a
      faith-based organization, an academic institution, and local government can
      successfully partner together to meet community needs.

PMID- 17214652
TI  - The syphilis elimination project: targeting the Hispanic community of Baltimore
      city.
AB  - OBJECTIVE: The objective of the Syphilis Elimination Project was to decrease the
      incidence of syphilis in the Hispanic community of Baltimore City through a
      culturally appropriate health initiative. DESIGN: Both qualitative and
      quantitative methods were used in the study design. Surveillance data were used
      to collect testing information. Comparisons at the start and end of the project
      measured change in individual knowledge about syphilis. Cross-sectional data from
      interviews with business owners and qualitative comments from outreach workers
      evaluated perception of program effectiveness. The local health department
      collected surveillance data. SAMPLE: A convenience sample of 63 Hispanic
      community members, 12 business owners/managers, and 8 outreach workers was
      utilized throughout the evaluation process. INTERVENTION: The project was a
      culturally appropriate approach to health promotion with street and business
      outreach. RESULTS: Post intervention there was a statistically significant
      increase in knowledge about syphilis within the Hispanic community and an
      increase in testing behaviors. CONCLUSIONS: The Syphilis Elimination Project was
      created in response to a marked increase in syphilis in Baltimore among the
      Hispanic population and a health disparity that existed within the city. It
      increased community members' knowledge of syphilis and positively influenced
      testing behaviors.

PMID- 17214653
TI  - Warned, but not well armed: preventing viral upper respiratory infections in
      households.
AB  - The purpose of this state-of-the-science review was to identify strategies and
      household-level interventions for public health nurses to help prevent the
      acquisition and spread of viral upper respiratory infections (URI) in the
      community. Even though viral URI are a major global economic and social problem,
      surprisingly little research has been conducted to attempt to prevent them or
      reduce their transmission, probably because URI (with the exception of epidemic
      influenza) are generally considered to be mild and self-limited. Based on the
      research to date, public health nurses can use several promising strategies for
      prevention: (a) provide more tailored educational messages regarding preventive
      strategies such as vaccination, hand hygiene, spatial separation of infected
      household members, avoidance of antibiotics to treat viral URI, and environmental
      cleaning (e.g., for toys or other shared items), which are delivered personally
      rather than passively (e.g., pamphlets placed in a waiting room); (b) use each
      patient encounter in any setting to encourage influenza vaccination for relevant
      risk groups; (c) encourage use of alcohol hand sanitizers by household members
      during the cold and flu season; and (d) provide opportunities for skill
      development for adult and child household members (e.g., cover your cough, when
      to seek care or an antibiotic).

PMID- 17214654
TI  - Improving the selective neonatal BCG program.
AB  - OBJECTIVES: The aim of the work was to develop and implement an improved
      selective neonatal Bacille-Calmette-Guerin (BCG) vaccine program in which
      neonates are systematically assessed, and those identified as at "high risk of
      being exposed to tuberculosis" are given neonatal BCG. DESIGN: Service models
      used in other parts of the country were assessed and their limitations and
      difficulties were carefully considered. Possible service models for local use
      were then considered. A selective neonatal BCG program involving universal
      neonatal screening was implemented. SAMPLE: A program was implemented offering
      BCG to high-risk neonates. RESULTS: As has been the case with other health
      trusts, developing a new neonatal BCG service met with obstacles and hurdles.
      Means of overcoming some of the difficulties are presented. Preliminary findings
      regarding the service model, including neonatal BCG uptake rates, were positive.
      CONCLUSION: A successful neonatal BCG program was implemented.

PMID- 17214655
TI  - Preparing public health nurses for pandemic influenza through distance learning.
AB  - As a global influenza pandemic appears imminent with the spread of avian
      influenza, the California Department of Health Services (CDHS) and the California
      Distance Learning Health Network (CDLHN) presented a live 90-min satellite
      broadcast and subsequent 2-hr small group problem-solving tabletop exercise to
      practice interventions needed to minimize the consequences of a pandemic event.
      Public health nurses (PHNs), managers, and other staff in laboratories, clinical
      care, veterinary medicine, environmental health, public information and safety,
      emergency management, and transportation down linked the program, broadcast by
      satellite from the CDHS Richmond Laboratory Campus, to view on-site locally. PHNs
      represented the professional category with the highest number of participants for
      those conducting the program outside of California. For those in California, PHNs
      represented the professional category with the second highest number of
      participants. Participants and distance-learning facilitators completed a
      training evaluation survey. Continuing education credits were provided by the
      Centers for Disease Control and Prevention to participants who completed the
      satellite broadcast evaluation. This distance-learning-by-satellite method of
      education paired with an activities-based tabletop exercise, and a focus on local
      rather than State-based responsibility, marks an innovative method of training
      PHNs and other staff in emergency preparedness response.

PMID- 17214656
TI  - Social justice: added metaparadigm concept for urban health nursing.
AB  - Historically, the nursing metaparadigm has been used to describe 4 concepts of
      nursing knowledge (person, environment, health, and nursing) that reflect beliefs
      held by the profession about nursing's context and content. The authors offer an
      assessment of the metaparadigm as it applies to community and public health
      nursing in urban settings and offer an amendment of the metaparadigm to include
      the central concept of social justice. Each of the metaparadigm concepts and the
      central concept of social justice is discussed as it applies to a model of urban
      health nursing teaching, research, and practice.

PMID- 17214657
TI  - A relationship power scale for female adolescents: preliminary development and
      psychometric testing.
AB  - OBJECTIVES: To develop and test psychometric characteristics of the Relationship
      Power Scale (RPS), which can be used to explore the relationship power of female
      adolescents in heterosexual relationships. METHODS: Cross-sectional design.
      Female adolescents in Kaohsiung City, Taiwan, who had a steady relationship with
      a boyfriend at the time of the study were recruited as study subjects (n=414) to
      test validity and reliability of the RPS. RESULTS: Confirmatory factor analysis
      revealed that a one-factor model with correlated uniqueness among the positively
      worded items best fits the data. There were significantly different scores in 3
      different response groups on 2 items regarding who (participants, both themselves
      and their boyfriends equally, or their boyfriends) had more power in the
      relationship, and who was more emotionally involved in the relationship for all
      subjects. For subjects having sex with their steady boyfriends, RPS scores
      significantly differ among the 3 different response groups on 2 items regarding
      who had more say about having sex, and who had more say about using condoms.
      Cronbach's alpha for the RPS was .69. Test-retest reliability coefficients for
      the RPS were .83. CONCLUSIONS: The RPS exhibited acceptable reliability and
      validity. Further research is recommended to use the RPS in sex-related behavior
      research among heterosexual female adolescents.

PMID- 17214658
TI  - From the Grey Nuns to the streets: a critical history of outreach nursing in
      Canada.
AB  - This article traces the historic antecedents of outreach nursing in Canada, going
      as far back as the Grey Nuns in what is now Quebec. It attempts to place modern
      day street nursing in a historical context, which includes Nightingale, Wald, the
      early Victorian Order of Nurses, and the social reform movements of the early
      20th century. The article critiques the involvement of nursing in less than
      virtuous aspects of social control with respect to impoverished and otherwise
      marginalized groups. The article goes on to trace the origins of modern Canadian
      street nursing in three cities: Vancouver, Toronto, and Montreal. It uses both a
      search of the nursing literature and, because much of this history is
      undocumented, oral history and anecdotal information as well. It critiques
      nursing's traditional avoidance of political action and calls upon modern-day
      nurses to support and educate one another to engage in this work.

PMID- 17214659
TI  - Quantitation of sleep and spinal curvature in an unusually longevous owl monkey
      (Aotus azarae).
AB  - BACKGROUND: A table summarizing the primary literature on 19 species of longevous
      non-human primates, other than owl monkey, is presented. METHODS: We
      prospectively quantitated the sleep of a longevous female owl monkey (Aotus
      azarae), aged >30 years, longitudinally for 2 years and also evaluated the
      senility-induced change in spinal curvature. RESULTS: The mean daily total sleep
      time (TST) of this monkey ranged between 790 and 1106 minutes, and was markedly
      higher in comparison with its female progeny (aged 16 years and used as a
      control) whose daily TST during the same experimental period ranged between 612
      and 822 minutes. CONCLUSIONS: The calculated kyphotic index (KI) of 2.27 for this
      monkey, compared with the KIs 4.83 and 5.42, for its progeny and female
      grandprogeny (aged 1 year) respectively, confirmed the prominent spinal
      curvature.

PMID- 17214660
TI  - Morphometric and hormonal changes during the chimpanzee menstrual cycle.
AB  - BACKGROUND: Sex steroids affect many peripheral tissue sites in female mammals.
      Receptors for these hormones have been found in skin, fat, and bone. In women,
      these tissues can show morphological changes during the menstrual cycle that may
      be directly related to steroid secretion. METHODS: The present study was done on
      chimpanzees to document morphometric markers associated with these tissues
      (anogenital swelling volume, skin fold thickness as indicator of subcutaneous
      fat, bony diameters of mandible, wrist, and elbow) and to compare them with
      cyclic patterns of estradiol, progesterone, testosterone, gonadotropins, and
      prolactin. RESULTS: Swelling volume changed significantly over the menstrual
      cycle. All other morphometric parameters showed variation without statistical
      significance. Skin folds were thickest during the luteal phase. Bony diameters
      displayed similar but less distinctive changes. Testosterone correlated
      positively with diameter sites, inversely with subcutaneous fat. No relationships
      with either estradiol or progesterone were found. We assume that subcutaneous fat
      and morphometric bone parameters exhibit cycle-dependent changes that may be
      caused by changes in steroid secretion.

PMID- 17214661
TI  - Alteration of the menstrual cycle in baboons placed on tethering devices and
      moved to individual housing--a stress model for a follicular phase defect.
AB  - BACKGROUND: During an attempt to identify endocrine characteristics in the baboon
      that would more precisely predict ovulatory status for assisted reproductive
      techniques, we observed severe alterations in the menstrual cycle length upon
      introducing an environmental stress. This environmental stress involved moving
      animals from their baseline gang cage environment to individual indoor caging and
      placing them on a tethering apparatus. METHODS: Five adult female baboons were
      followed for changes in sex skin indicative of menstrual cycle timing and move
      from outdoor gang gages to individual indoor cages during the early follicular
      phase of their cycle. A tether device including a surgically implanted cannula
      was then installed to facilitate daily blood draws without sedation.
      Radioimmuonoassays were performed to monitor serum estradiol levels and
      lapraroscopic surveillance was used to confirm time of ovulation. RESULTS:
      Complete data sets were collected from four of the female baboons. In each case,
      a prolongation of the menstrual cycle was noted either during the cycle during
      which the females were moved to indoor caging or during the cycle immediately
      following the move. This prolongation was isolated to the follicular phase of the
      affected cycle. CONCLUSIONS: We conclude that otherwise normal handling
      procedures, including movement to new caging, and/or installation of a tether
      device, can impart a stress effect on reproductively cycling adult female
      baboons, such that folliculogenesis is delayed.

PMID- 17214662
TI  - A comparison of non-contact, subcutaneous, and rectal temperatures in captive owl
      monkeys (Aotus sp.).
AB  - BACKGROUND: Three methods of body temperature measurement were compared in owl
      monkeys: non-contact infrared thermometry, subcutaneous transponder, and rectal
      probe. METHODS: Forty owl monkeys (Aotus sp.) were used. Animals were implanted
      with subcutaneous microchip transponders. Infrared thermometry was used at three
      different sites. All measurements were taken and repeated randomly. RESULTS:
      Infrared and subcutaneous measurements did not agree well with rectal
      thermometry. Subcutaneous and rectal temperatures were highly repeatable, and
      subcutaneous temperatures were most agreeable to rectal temperatures.
      CONCLUSIONS: Further investigation is needed into subcutaneous implant sites and
      use of different infrared thermometers in this species.

PMID- 17214663
TI  - Factors contributing to spontaneous Enterocytozoon bieneusi infection in simian
      immunodeficiency virus-infected macaques.
AB  - BACKGROUND: A cohort of SIV-infected macaques had been used to investigate the
      effect of dietary supplement, immune status, SIV/AIDS disease progression and
      serum micronutrients levels on spontaneous acquisition of Enterocytozoon bieneusi
      infection in SIV-infected macaques. METHODS: Twenty-four SIV-infected macaques
      were randomized into 2 groups. One group received a vitamin/mineral
      supplementation and a second group received a placebo. Both groups were examined
      for E. bieneusi infection. RESULTS: SIV-infected macaques were more prone to
      acquire E. bieneusi with the progression of SIV/AIDS, and the increased shedding
      of infectious spores was directly associated with decreased CD4 lymphocyte and
      increased circulating SIV, in both supplemented and unsupplemented groups of
      animals. Dietary supplementation, body composition factors and serum
      micronutrients levels however had no association with the acquisition of E.
      bieneusi infection in these animals. CONCLUSIONS: Acquisition of E. bieneusi
      infection is related to SIV disease progression, CD4 counts and viral load but
      independent of changes in body composition and serum micronutrient levels.

PMID- 17214664
TI  - GnRH-antagonist mediated down-regulation of the estrous cycle in marmosets.
AB  - BACKGROUND: Because of its small size and unproblematic captivity behavior the
      marmoset monkey is an attractive New World primate model for early developmental
      questions. However, superovulation protocols used in Old World monkeys and women
      are not successful in the female marmoset. A novel protocol is needed to utilize
      these New World monkeys as an efficient animal model for in vitro fertilization
      experiments or embryo stem cell research. METHODS: To create such a protocol we
      first examined the effects of long-term estrous cycle control, secondly, in a
      dose-finding study, we determined the length of a down-regulation protocol with a
      gonadotropic releasing hormone (GnRH)-antagonist. Twenty-nine female marmosets
      were grouped according to the number of estrous cycles, which had been controlled
      for a period of 12 months in which 88 cycles were monitored. Application of
      PGF2alpha in the mid-luteal phase led to immediate onset of the follicular phase.
      The blood progesterone concentration rapidly declined and increased again on day
      9-11. RESULTS: The results show that the controlled ovarian cycle length and
      progesterone response are not altered by the number of PGF2alpha injections. The
      rapid decline was similar in all groups, indicating that all animals, independent
      of the number of controlled cycles, react equally to multiple PGF2alpha
      injections. To determine the proper dosage for a GnRH-antagonist (Cetrorelix), 12
      animals in three groups of four female marmosets were treated with two different
      dosages and a sham dosage. Cetrorelix was applied in the mid-luteal phase, three
      times over 2 days. In both Cetrorelix-treated animal groups the early
      progesterone levels matched those in the controls. In the low-dose treatment
      group [0.01 mg/100 g body weight (BW)] the expected progesterone rise on day 10
      was delayed between 9 and 15 days whereas in the high-dose treatment group (0.1
      mg/100 g BW) the progesterone rise was delayed between 21 and 41 days. In the low
      dose group the steepness of the slope from day 20 onwards was almost identical to
      that of the control group. This was reflected in the bioCG levels measured.
      CONCLUSIONS: Based on the GnRH-antagonist studies, complete ovarian down
      regulation in female marmosets can be achieved by applying a low-dose regimen,
      and intrinsic gonadotropins would not interfere with an ovarian superstimulation
      protocol.

PMID- 17214665
TI  - Differential distribution of antibodies to different viruses in young animals in
      the free-ranging rhesus macaques of Cayo Santiago.
AB  - BACKGROUND: The breeding colony of free-ranging rhesus macaques was established
      in 1938 in Cayo Santiago (CS) with animals collected in northern India. The
      seroprevalence to cercopithecine herpesvirus type 1 (B virus) and simian
      retroviruses has been studied previously. RESULTS: This is the first report on
      the seropositivity to different viruses using samples collected shortly after
      removing animals (n = 245) from CS. All samples were negative for measles, simian
      immunodeficiency virus and simian type D retroviruses. The overall prevalence of
      antibodies was around 50% for simian T-lymphotropic virus I (STLV-I). For B
      virus, the prevalence was 38%. CONCLUSIONS: Data obtained showed marked
      differences in the antibody distribution to B virus and STLV-I within the free
      ranging colony of rhesus macaques. Implication of these data for the Specific
      Pathogen Free program at the Caribbean Primate Research Center are also
      discussed.

PMID- 17214666
TI  - Molecular cloning and gene expression of endoplasmic reticulum stress proteins in
      Japanese monkey, Macaca fuscata.
AB  - BACKGROUND: Immunoglobulin heavy-chain binding protein (BiP), calreticulin (Crt),
      and protein disulfide isomerase (PDI), are major resident endoplasmic reticulum
      (ER) stress proteins which are involved in diverse roles relating to successful
      folding, assembly, intracellular localization, and degradation of other proteins.
      METHODS: In this study, we molecular cloned cDNAs for BiP, Crt, and PDI from
      Japanese monkey (Macaca fuscata), and analyzed tissue-specific expression of
      respective genes. RESULTS AND CONCLUSIONS: The lengths of protein-coding regions
      of these cDNAs for BiP, Crt and PDI are 1965, 1254, and 1533 bp, respectively.
      Each protein has a signal peptide and a KDEL motif in N- and C-terminal parts
      respectively, showing its intracellular localization to be the lumen of the ER.
      These stress proteins are highly conserved, showing that their similarities among
      mammals are more than 90% in the level of amino acid. The expression of the genes
      for stress proteins differed among the monkey tissues examined. BiP and PDI gene
      expression was predominant in secretory tissues such as liver and kidney, and
      brain tissues. But Crt gene expressed rather ubiquitously in a variety of
      tissues.

PMID- 17214667
TI  - Hepatitis viruses in non-human primates.
AB  - BACKGROUND: Previous epidemiological studies of rural human populations in Gabon
      reveal a high prevalence of human hepatitis A, B, C and D viruses. In order to
      investigate the prevalence of the blood-born hepatitis viruses in apes and
      monkeys living in the same area, we performed an epidemiological survey of HBV,
      HCV and HDV in wild-born non-human primates. METHODS: We tested 441 wild-born non
      human primates from Gabon and Congo and 132 imported monkeys for the presence of
      serological markers of HBV, HCV and HDV infections. RESULTS: None of
      Cercopithecidae monkeys were reactive against HBV/HDV and HCV. In contrast, 29.2%
      of wild-born great apes (154 chimpanzees and 14 gorillas) were positive for HBV
      serological markers. Nine chimpanzees were in the replicative phase of HBV
      infection. None of these HBV infected chimpanzees exhibited symptoms or
      significant changes in serum clinical chemistry related to HBV infection.
      CONCLUSIONS: The negativity to HCV-related viruses and the negativity of the
      Cercopithecidae species tested against HBV/HDV do not allow us to definitively
      rule out the presence of an animal counterpart of human hepatitis viruses in non
      human primates.

PMID- 17214668
TI  - Objective measures of health and well-being in laboratory rhesus monkeys (Macaca
      mulatta).
AB  - BACKGROUND: Non-human primates are an invaluable part of biomedical research.
      Strict regulations insure animals have a maximum likelihood of well-being and
      optimum health during the course of experimental procedures. Objective assessment
      of well-being is a critical component of these assurances. METHODS: Here we
      describe an objective and quantitative system we used to identify two well-being
      concerns in laboratory rhesus monkeys (Macaca mulatta). We provide a series of
      indicators for use by laboratory personnel to promote laboratory primate well
      being. The indicators measure (1) potentially life threatening clinical concerns,
      (2) developing clinical issues, (3) atypical behaviors, and (4) laboratory
      performance. We include specific criteria to facilitate veterinary intervention.
      RESULTS: The assessment, applied to two case studies reported here, enabled swift
      veterinary intervention returning the animals to a healthy state. CONCLUSIONS:
      The measures described here provide a battery of observable and objective
      measures across multiple dimensions that can further ensure both excellent
      science and veterinary care.

PMID- 17214669
TI  - Electromyographic telemetry in the development of humane primate model of spinal
      cord injury.

PMID- 17214670
TI  - Model of traumatic spinal cord injury in Macaca fascicularis: similarity of
      experimental lesions created by epidural catheter to human spinal cord injury.

PMID- 17214671
TI  - Monoclonal antibody testing.

PMID- 17214672
TI  - Multiple primary acral melanomas in African-Americans: a case series and review
      of the literature.
AB  - BACKGROUND: Although melanoma accounts for only 4% to 5% of all skin cancers in
      the United States, it causes most skin cancer-related deaths. We describe a
      unique group of African-American patients with multiple primary acral lentiginous
      melanomas (ALMs). OBJECTIVE: The purpose of this study was to review the case
      histories and management of a cohort of patients in the Mohs practice of our
      dermatologic surgeon with multiple primary ALM. METHODS: This is a case series of
      patients with multiple ALM identified by chart review from 2000 to 2005. A
      thorough review of the literature was performed. RESULTS: Four patients, all
      African-American, were identified with multiple ALM. All patients were managed
      with excision or Mohs micrographic surgery utilizing permanent sections. None of
      the patients with ALM had melanomas at nonacral sites or other types of skin
      cancer. Several had acral melanosis. Information in the literature on patients
      with multiple primary acral melanomas was insufficient. CONCLUSION: Patients with
      multiple acral melanomas have not, to our knowledge, been reported thus far. It
      can be extrapolated from current literature, however, that appropriate management
      of these patients, including staging work and surgical intervention, is to be
      determined by the individual characteristics of the melanoma and the patient's
      concomitant risk factors, if any.

PMID- 17214673
TI  - Interferon Alfa-2b or not 2b? Significant differences exist in the decision
      making process between melanoma patients who accept or decline high-dose adjuvant
      interferon Alfa-2b treatment.
AB  - BACKGROUND: Patients with thick (Breslow>4 mm) primary melanoma and/or regional
      nodal metastasis have a high risk of tumor recurrence. High-dose adjuvant
      interferon (IFN) alfa-2b offers<or=10% improvement in relapse-free survival and
      overall survival with significant toxicity. OBJECTIVE: The objective was to
      determine which prognostic factors and patient characteristics are significant in
      the decision to undergo IFN therapy. METHODS: Of 781 patients who underwent
      sentinel lymph node (SLN) biopsy, 135 of 781 (17.3%) had positive SLN or thick
      melanomas and were informed of a >/=50% risk of recurrence/disease-related
      mortality and offered IFN. Telephone surveys delineated reasons behind patients'
      decisions to accept IFN. RESULTS: Acceptors, 60 of 135 (45%), decided to take IFN
      alfa-2b whereas 75 of 135 (55%) declined. Being female (OR, 2.4; 95% CI, 1.17
      5.03; p=.017) and positive SLN status (OR, 2.2; 95% CI, 1.01-4.97; p=.048) were
      strongly associated with patients who chose IFN. Acceptors of IFN were younger,
      more influenced by physicians, and less affected by depression and side effect
      profile (p<.05 for all). Decliners were more concerned by strained relationships
      with family and social life (p<.05). CONCLUSIONS: Gender and positive SLN were
      predictive of high-risk melanoma patients' acceptance of IFN treatment. Physician
      insight into melanoma patients' therapeutic decision-making process can guide
      patients through this difficult disease.

PMID- 17214674
TI  - The "drumhead" graft repair of deep nasal alar defects.
AB  - BACKGROUND: Extirpation of tumors on the perialar region often results in deep
      surgical defects. The nares and internal nasal valves are supported not just by
      alar cartilage, but also by the suspension effect of the overlying skin and
      subcutaneous tissue. Surgical loss of tissue may result in inward collapse of the
      nasal vestibule with resultant difficulty in breathing. The use of full-thickness
      skin grafts (FTSGs) on deep alar defects commonly results in a sunken or
      depressed graft that is functionally and cosmetically unacceptable. OBJECTIVE: We
      describe a novel technique that enables the use of FTSGs in the repair of deep
      nasal alar defects through the application of an overlying, rigid plastic
      suspension strut coupled with an undersized graft. RESULTS: The drumhead FTSG is
      effective in preventing collapse of the nasal vestibule as well as undesirable
      contour irregularities due to a depressed or sunken graft. Patients were seen at
      1 week, 4 weeks, and 3 months postoperatively. At each time point, there was no
      nasal vestibular collapse and only very slight graft depression, which replicated
      the normal mild concavity of the alar crease region. All patients had excellent
      functional and cosmetic outcomes. No adverse effects were noted. CONCLUSION: The
      "drumhead" graft is a novel technique, which enables the use of FTSGs for deep
      alar defects by inhibiting undesirable depression of the graft and preventing
      collapse of the nasal vestibule.

PMID- 17214675
TI  - Fractional photothermolysis: treatment of facial and nonfacial cutaneous
      photodamage with a 1,550-nm erbium-doped fiber laser.
AB  - PURPOSE: To evaluate the safety and effectiveness of a novel nonablative 1,550 nm
      erbium-doped fiber laser in the treatment of facial and non-facial photodamaged
      skin. METHODS: 50 patients with mild to moderate cutaneous photodamage, rhytides,
      and dyspigmentation received 3 successive treatments at 3-4 week intervals with a
      1,550 nm erbium-doped fiber laser (Fraxel, Reliant Technologies Inc., San Diego,
      CA). Clinical improvement of treatment areas was independently determined by two
      masked assessors' evaluations of comparative photographs at baseline and 3, 6,
      and 9 months post-treatment using a quartile grading scale. Patient satisfaction
      surveys were also obtained at each follow-up visit. RESULTS: Mean clinical
      improvement at 3 months for the face was 2.23 and 1.85 for non-facial skin
      (p<0.001). Mean improvement at 6 months was 2.10 for the face and 1.81 for non
      facial skin (p<0.001). Mean improvement at 9 months was 1.96 for the face and
      1.70 for non-facial skin (p<0.001). At least 51% to 75% improvement in
      photodamage at the 9-month follow-up was achieved in 73 and 55% of facial and non
      facial treated skin, respectively. Side effects were limited to transient
      erythema and edema in the majority of patients. No prolonged pigmentary changes
      or scarring were observed. Patient satisfaction surveys mirrored the observed
      clinical effects. CONCLUSION: The nonablative 1,550 nm erbium-doped fiber laser
      is an effective treatment for facial and non-facial photodamage, rhytides, and
      dyspigmentation with a favorable recovery and side effect profile.

PMID- 17214676
TI  - Radiofrequency and 585-nm pulsed dye laser treatment of striae distensae: a
      report of 37 Asian patients.
AB  - BACKGROUND: Various lasers have recently been reported as effective treatment
      modalities for striae distensae, but pigmentary alterations are a major concern
      to the darker skin type. The Thermage (Therma Cool TC; Thermage Inc, Hayward, CA)
      is a radiofrequency device for the lifting of face and neck, and there is no
      report of using it for striae distensae. OBJECTIVE: The purpose was to evaluate
      the effectiveness of the Thermage in combination with pulsed dye laser. MATERIALS
      AND METHODS: Thirty-seven patients with abdominal striae distensae were treated
      with the Thermage and 585-nm pulsed dye laser in the first session at baseline.
      An additional two sessions of pulsed dye laser were performed at Weeks 4 and 8.
      Thermage was used at fluences of 53 to 97 J/cm2 and pulsed dye laser at fluences
      of 3.0 J/cm2 with 10-mm spot. Skin biopsies were taken of nine patients. RESULTS:
      In the subjective assessment, 89.2% of the patients showed "good and very good"
      to overall improvement, and 59.4% were graded as "good and very good" in
      elasticity. All of the nine specimens showed an increase in the amount of
      collagen fibers, and increased elastic fibers were found in six specimens.
      CONCLUSION: The Thermage and pulsed dye laser appear to be an effective treatment
      for striae distansae.

PMID- 17214677
TI  - Artificial hair fiber restoration in the treatment of scalp scars.
AB  - BACKGROUND: There is presently no treatment for scalp scars that is fully
      satisfactory. The modalities of treatment currently in use are surgery, hair
      transplantation, and micropigmentation. Scalp implantation with artificial hair
      fibers is used by some physicians as an adjunctive treatment. OBJECTIVE: The
      objective was to assess the utility of artificial hair fibers to treat scalp
      scars. METHODS: Data were collected by the principal author from 10 hair
      restoration practitioners who tested polyamide hair fiber (Biofibre CE 0373/TGA
      by Medicap Ltd., Carpi (MO), Italy) implantation for scalp scars. RESULTS:
      Artificial hair fiber implantation occurred between June 1996 and December 2000,
      and observations continued until December 2004. Data from 54 scars from 44
      patients treated showed: (1) no complications in 49 scars (90.7%); (2) mild
      adverse outcomes in 4 scars (7.4%)-temporary superficial inflammation-infection
      that subsided following topical cortisone and local/systemic antibiotic
      treatment; and (3) moderately adverse outcomes in 1 scar (1.9%)-significant
      inflammation and generalized infection requiring removal of artificial implant to
      alleviate. Occasional minor skin reactions, sebum plugs, and hyperseborrhea were
      successfully controlled and well accepted by patients. Fiber fall rate was 20% on
      average per annum. CONCLUSION: Data show that polyamide hair fiber restoration
      can be considered an adjunctive treatment for scalp scars in selected cases.

PMID- 17214678
TI  - Minimal scars for scalp surgery.
AB  - BACKGROUND: As is well known, scars are the indelible ransom of any surgical
      procedure and the major obstacle confronting patients and surgeons from an
      aesthetic standpoint. Many patients opt against a surgical solution for this
      reason only or choose surgical techniques which are sometimes open to question,
      such as follicular unit extraction. OBJECTIVE: The objective was to change from
      narrow scars created at present to that of scars minimal to the naked eye, the
      subject of this article. METHODS: Following a clinical study of more than 100
      cases, I present a new surgical technique enabling for the first time the
      creation of minimal scars to the naked eye. This technique is based on the role
      of the galea responsible for tension and secondary widening of scars in classical
      techniques and explains hypodermic incision to eliminate this wound tension, as
      well as the specific role of deepithelialization of the lower lip of the wound.
      RESULT: A minimal scar to the naked eye was obtained in most cases with this
      technique. CONCLUSION: Owing to this major improvement, I have switched from the
      conventional closure techniques to this new one.

PMID- 17214679
TI  - Control of palmar hyperhidrosis with a new "dry-type" iontophoretic device.
AB  - BACKGROUND: Palmar hyperhidrosis is characterized by excessive sweating on the
      palm, and among the various treatment modalities, tap water iontophoresis has
      been widely used. OBJECTIVE: The objective of this study was to assess the effect
      of a new "dry-type" iontophoretic device that was locally manufactured and did
      not use tap water to control sweating. METHODS: Ten subjects with palmar
      hyperhidrosis were enrolled in this study. To be treated the patients were
      instructed that they only have to grasp the device. Only one palm was treated for
      2 weeks, and then the treatment was discontinued the following next 2 weeks. The
      other palm was not treated as a control. At the end of second week, biopsy
      specimens were obtained from untreated and treated palm, respectively, and
      examined histologically. RESULTS: Nine of 10 patients were satisfied with this
      therapy reducing their sweat outputs from 33% to 51% of baseline at the end of 2
      weeks' treatment, and after 2 weeks of discontinuation of treatment sweat
      productions returned to near baseline. The pathologic examinations showed some
      occlusions and destruction of intraepithelial eccrine ducts only in the treated
      palm. CONCLUSION: We suggest that dry-type iontophoresis could reduce palmar
      sweating more conveniently than other conventional methods.

PMID- 17214680
TI  - Cost-effective dynamic telepathology in the Mohs surgery laboratory utilizing
      iChat AV videoconferencing software.
AB  - BACKGROUND: Dynamic telepathology is the real-time transmission of histologic
      images from one pathologist to another by means of telecommunications technology.
      OBJECTIVE: The objective was to determine whether dynamic telepathology can be
      accomplished accurately and inexpensively by use of readily available off-the
      shelf consumer products and software. METHODS: We attached a standard, consumer
      grade, digital video camera to a microscope in the Mohs surgery laboratory and
      then transmitted via the Internet real-time histologic video images and audio to
      a consultant dermatopathologist by means of iChat AV videoconferencing software
      (Apple Computer Inc., Cupertino, CA). In the first part of the study, 20 unknown
      formalin-fixed, paraffin-embedded slides from tumors typically seen in a Mohs
      practice were evaluated by the consultant dermatopathologist. In the second part
      of the study, the Mohs surgeon consulted the dermatopathologist on 20 Mohs frozen
      section slides in which the surgeon had a particular question (e.g., "Is this
      part of a pilosebaceous unit or is this basal cell carcinoma?"). RESULTS: The
      video images were adequate for pathologic interpretation. There was agreement
      between conventional light microscopy and dynamic telepathology diagnosis in 19
      of 20 tumors. There was complete agreement for all 20 Mohs frozen section
      consultations. CONCLUSION: Dynamic telepathology can be accomplished accurately
      and inexpensively by use of readily available consumer products and software.

PMID- 17214681
TI  - Earlier detection of patients' second primary basal cell carcinomas: a
      quantitative analysis.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common occurring cancer in
      humans. No studies to date have compared the size of a patient's first and second
      primary BCC to determine whether we are detecting and treating second primary
      cancers at earlier stages of development. OBJECTIVE: The objective was to
      ascertain whether patients who have had a primary BCC are diagnosed and treated
      for subsequent BCC at an earlier clinical stage of development. METHODS AND
      MATERIALS: We performed a 4-year retrospective chart review of all patients
      presenting for Mohs micrographic surgery for two separate primary BCC. We
      compared the presenting clinical size of patients' first and second primary BCC.
      RESULTS: We found a statistically significant decrease in size of the second
      primary BCC when compared to the first primary BCC (p<.0001). The mean difference
      was 116.6 mm2 and the median difference was 28.3 mm2. CONCLUSION: Our results
      provide important quantitative data illustrating our effectiveness in detecting
      subsequent BCC at an earlier stage of development. Earlier detection of skin
      cancers can decrease the morbidity and chance of recurrence as well as lead to
      smaller scars and better cosmetic outcomes and may also allow for various
      treatment modalities and cost containment.

PMID- 17214682
TI  - Buffalo hump: spindle cell lipoma in posterior part of the neck.

PMID- 17214683
TI  - Crescentic nasojugal flap for nasal tip reconstruction.
AB  - BACKGROUND: Carcinomas of the tip of the nose are very common, and the nasal tip
      defect is one of the most challenging subunit to reconstruct. There are numerous
      available procedures for the reconstruction of the tip of the nose. We have
      developed a flap for the management of a tissue loss from the tip of the nose and
      report the use of this flap for 11 patients. OBJECTIVE: The purpose of this
      presentation is to report a refinement of a nasojugal flap for the reconstruction
      of a nasal tip defect. The flap we describe has the characteristic of excising
      the dog-ear, created by the movement of the flap, in a crescent shape of skin in
      the perialar area, allowing the mobilization of the skin of the lateral surface
      of the nose and cheek. METHODS: Eleven patients presenting tissue loss from the
      tip of the nose after excision of carcinoma underwent surgery using the flap.
      RESULTS: The flap described constitutes a good alternative for reconstruction of
      nasal tip defect, up to 2 cm of diameter, with excellent aesthetic results.
      CONCLUSION: Numerous flap options are available to reconstruct tissue loss from
      the tip of the nose. The nasojugal flap we describe, due to its great
      reliability, yields excellent functional and cosmetic results, and we believe
      that it is a valuable alternative to other techniques of reconstruction for
      defect of the nasal tip. For the 11 patients who underwent surgery with this
      flap, no major complication was reported. The aesthetic result was never
      compromised, and the scars result was very satisfactory.

PMID- 17214684
TI  - The vein hook successfully used for eradication of steatocystoma multiplex.
AB  - BACKGROUND: Steatocystoma multiplex is characterized by the formation of the
      numerous cutaneous cysts in the exposed area leaving some cosmetic problems for
      the patients. Only surgical excision has been effective, and its several
      variations were done with limited success. Because the patients usually have many
      cysts, excision of cysts was tedious for the doctors and left scars on the
      patients. METHOD: Five patients agreeing to participate in this experiments were
      selected. The vein hook used for ambulatory phlebectomy was employed to eradicate
      the cysts. The skin was incised approximately 2 to 3 mm in length. Then the
      mosquito forceps removed the cysts by gently squeezing or hooking the inner or
      outer cyst wall. By completely removing tissue around the cyst, recurrence was
      able to be prevented. RESULT: It took approximately 1 minute to excise one cyst
      completely, it left no hypertrophic scars except for transient postinflammatory
      hyperpigmentation, and it had no recurrences for 14 to 30 months on five
      patients. CONCLUSION: The use of this instrument is very simple and time-saving,
      providing excellent success rate with favorable cosmetic results. It can be a
      good alternative for eradication of the cysts in steatocystma multiplex. The
      authors have indicated no significant interest with commercial supporters.

PMID- 17214685
TI  - O to Z reconstruction of central upper lip defect.

PMID- 17214687
TI  - Dermoscopic features of difficult melanoma.
AB  - BACKGROUND: The dermoscopic diagnosis of cutaneous melanoma (CM) may be difficult
      because some CM lack specific dermoscopic features for melanoma diagnosis.
      OBJECTIVE: To evaluate whether a diagnosis of CM could be achieved using the
      classic dermoscopic melanoma-specific criteria, we conducted a retrospective
      multicenter study of 508 CM samples. METHODS: All the dermoscopic images were
      analyzed to identify the dermoscopic criteria found in dermoscopically difficult
      melanomas (DDM) and to examine the possible relation of dermoscopic diagnosis
      with respect to the difficulty of the dermoscopic diagnosis and the melanoma
      thickness. RESULTS: A significant percentage of melanomas, 89 of 508 (17.5%),
      were DDM. The criteria leading to a significant increased risk of DDM were
      presence of streaks [odds ratio (OR), 2.26; 95% confidence interval (CI), 1.15
      4.47), absence or presence of regular pigmentation (OR, 3.41; 95% CI, 1.70-6.85),
      absence of a blue-whitish veil (OR, 4.04; 95% CI, 2.33-6.99), absence of
      regression structures (OR, 4.31; 95% CI, 2.42-7.66), and the presence of
      hypopigmentation (OR, 2.61; 95% CI, 1.49-4.58). CONCLUSION: A significant number
      of melanomas defy even dermoscopic diagnosis. Only a meticulous comparative and
      interactive process based on an assessment of all the individual's other nevi
      ("ugly ducking" sign) and a knowledge about recent changes can lead to the
      recognition of DDM.

PMID- 17214688
TI  - Clearance of multiple venous lakes with an 800-nm diode laser: a novel approach.

PMID- 17214689
TI  - Pyogenic granuloma: satellitosis after carbon dioxide laser vaporization resolved
      with an intense pulsed light system.

PMID- 17214690
TI  - Atypical mycobacterial infections following cutaneous surgery.

PMID- 17214691
TI  - Temporal nerve neuropraxia and contralateral compensatory brow elevation.

PMID- 17214692
TI  - Recurrent invasive basal cell carcinoma after radiation and imiquimod: a case
      report.

PMID- 17214693
TI  - A case of tarsal conjunctival squamous cell carcinoma treated with Mohs
      micrographic surgery.

PMID- 17214694
TI  - Collision of malignant melanoma (lentigo maligna type) with squamous cell
      carcinoma in solar-damaged skin of the face.

PMID- 17214695
TI  - Tumescent liposuction with dermal curettage for treatment of axillary osmidrosis
      and hyperhidrosis.

PMID- 17214696
TI  - Visible incision lines and faulty design.

PMID- 17214697
TI  - The combined use of needle with hair transplanter for hair recipient sites.

PMID- 17214700
TI  - Coagulation and the xenograft endothelium.
AB  - Acute humoral rejection remains the major barrier to long-term pig-to-primate
      xenograft survival, and microvascular thrombosis is a critical element of the
      rejection process. It appears that persistent endothelial cell activation and
      injury, by even low levels of anti-graft antibodies, eventually overwhelm the
      cellular anticoagulant defences and promote the development of thrombotic
      microangiopathy. Porcine endothelium may be particularly vulnerable because of
      cross-species molecular incompatibilities affecting the function of
      thrombomodulin and possibly TFPI. Recent data from small animal models suggest
      that transgenic overexpression of anti-thrombotic molecules on xenograft
      endothelium is capable of inhibiting intravascular thrombosis and preventing
      acute humoral rejection. In conjunction with existing genetic modifications (e.g.
      Gal KO, hDAF), this is a promising strategy to move xenotransplantation to the
      clinic.

PMID- 17214701
TI  - Lack of evidence for PERV expression after apoptosis-mediated horizontal gene
      transfer between porcine and human cells.
AB  - Evidence for porcine endogenous retrovirus (PERV) infection of human cells has
      provoked a public health debate over the proposed use of porcine xenografts to
      alleviate the worldwide shortage of human allografts. Nevertheless, the potential
      relevance of PERV transmission by apoptosis-mediated horizontal DNA transfer, a
      documented means of infection-independent retrovirus delivery, appears to have
      been overlooked in this discussion. To examine the hypothesis that apoptotic cell
      death during porcine xenograft rejection is capable of fostering horizontal DNA
      transfer, we have now assessed in vitro cocultures, consisting of phagocytic
      human fibroblasts and apoptotic or necrotic porcine B-lymphoblastoid cells, for
      evidence of cross-species PERV exchange and eventual replication. Using real-time
      polymerase chain reaction (PCR) assays, designed to differentiate nuclear and
      cytoplasmic DNA derived from either porcine or human cells, we now report
      evidence for the presence of porcine DNA, including PERV, in the nucleus of human
      fibroblasts exposed to apoptotic porcine cells. This novel demonstration of
      apoptosis-mediated horizontal PERV transfer is characterized by a low efficiency
      of transfer and a transient nature, being present in only 0.22% of the cocultured
      human cells and disappearing to undetectable levels within 4 weeks of exposure to
      apoptotic porcine cells. In contrast, using PERV-specific real-time reverse
      transcriptase PCR (RT-PCR) and ultra-sensitive product-enhanced reverse
      transcriptase (PERT) assays, we find no evidence for human fibroblast-derived
      cellular PERV RNA or coculture supernatant-based RT-activity, indicating a lack
      of subsequent PERV replication. Together, these results suggest that apoptosis
      mediated horizontal PERV transfer does not present an overt hazard within the
      framework of porcine xenotransplantation. However, we also present arguments
      against extrapolation of these in vitro observations directly to clinical
      circumstances.

PMID- 17214702
TI  - Induction of regulatory cells and control of cellular but not vascular rejection
      by costimulation blockade in hamster-to-rat heart xenotransplantation.
AB  - BACKGROUND: In heart allograft in the rat, a sustained costimulation blockade
      with CTLA4Ig prevents alloreactive T-cell activation and promotes a long-term
      graft survival through the action of tolerogeneic dendritic cells. It is unclear
      whether similar mechanisms might occur after xenotransplantation. To test that
      hypothesis, we have analyzed the action of CTLA4Ig in a model of CD4(+)T cell
      mediated xenograft rejection. METHODS: Hamster hearts were transplanted into
      LEW.1A rats receiving an accommodation-inducing treatment consisting of a short
      course administration of LF15-0195 and a daily administration of cyclosporine A
      (CSA). To achieve long-term delivery of CTLA4Ig, an intravenous administration of
      an adenovirus vector coding for mouse CTLA4Ig (Ad-CTLA4Ig) was added to the
      accommodation induction protocol. On day 40 post-transplantation, rejection was
      induced by CSA withdrawal. In other xenograft recipients, CD28/B7 costimulation
      was inhibited at that time only by injections of CTLA4Ig or anti-CD28 antibodies.
      Graft survival, immunohistology, as well as development of antibodies and
      regulatory cells were examined. RESULTS: Xenografts survived 6 days after CSA
      withdrawal in controls and were rejected, as previously described, through the
      action of CD4(+) xenoreactive T cells. Interfering with CD28/B7 costimulation
      inhibited this xenoreactive T cell response and delayed rejection to day 10. In
      recipients that had received Ad-CTLA4Ig, survival was prolonged to day 19 and
      this was accompanied by the appearance of regulatory cells exhibiting non-donor
      specific suppressive activity dependent on IL-2, NO, and IDO. These regulatory
      cells were different from those previously identified after Ad-CTLA4Ig
      administration in heart allograft in the rat. In these recipients, rejection
      occurred as a consequence of an evoked anti-donor IgM response and complement
      activation and not of a cellular rejection as complement inhibition with cobra
      venom factor further prolonged xenograft survival. CONCLUSION: CD28/B7 blockade
      delays CD4(+) T cell-mediated rejection after CSA withdrawal in accommodated
      recipients of hamster heart xenografts. In addition, a sustained expression of
      CTLA4Ig has the potential of inducing cellular regulatory mechanisms. However,
      such treatment does not prevent the development of xenoreactive IgM antibodies
      that participate in vascular rejection processes in a complement-dependent
      manner.

PMID- 17214703
TI  - Coagulation cascade activation triggers early failure of pig hearts expressing
      human complement regulatory genes.
AB  - BACKGROUND: Hyperacute rejection (HAR) and early graft failure (EGF) have been
      described in a minority of pig-to-baboon heart transplants using organs
      transgenic for human complement regulatory proteins (hCRP). Here we investigate
      the role of coagulation cascade activation in the pathogenesis of HAR and EGF in
      a consecutive series where a high incidence of these outcomes was observed.
      METHODS: Twenty-eight naive wild-caught Papio anubis baboons received heterotopic
      heart transplants from pigs transgenic for hDAF (n = 23) or hMCP (n = 5).
      Immunosuppression consisted of cyclosporine A, cyclophosphamide and MMF (n = 18)
      or anti-CD154 mAb (IDEC-131) and ATG (n = 10). Eleven received anti-Gal
      carbohydrates (GAS914, n = 8, or NEX1285, n = 3), of which four also underwent
      extracorporeal immunoadsorption (EIA), and 12 also received pharmacologic
      complement inhibitors (C1 INH, n = 9, or APT070, n = 3). RESULTS: Excluding one
      technical failure, 14 of 27 transplants (11 hDAF, 3 hMCP) exhibited either HAR (n
      = 10) or EGF (n = 4). Surprisingly, neither complement inhibition (with C1 INH or
      APT070) nor anti-Gal antibody depletion with GAS914, NEX1285, or additional EIA
      consistently prevented HAR or EGF despite low or undetectable complement
      deposition. Strikingly, most grafts with HAR/EGF exhibited prominent fibrinogen
      and platelet deposition associated with systemic coagulation cascade activation,
      consistent with non-physiologic intravascular coagulation, in many instances
      despite little evidence for antibody-mediated complement activation. CONCLUSION:
      We conclude that dysregulated coagulation correlates closely with and probably
      causes primary failure of pig hearts transgenic for hCRP. These data support
      efforts to define effective strategies to prevent dysregulated coagulation in pig
      organ xenografts.

PMID- 17214704
TI  - Chemokine and toll-like receptor signaling in macrophage mediated islet xenograft
      rejection.
AB  - BACKGROUND: Adoptive transfer of antigen-primed T-cell-activated macrophages into
      NOD-SCID mice within 14 days of foetal porcine pancreatic fragment (FPP) or
      foetal porcine skin (FPS) transplantation had been shown to cause xenograft
      rejection. In the present study, it was proposed that signaling between the graft
      and macrophages promoted specific graft recognition and destruction in this
      setting. METHODS: Exogenous macrophages isolated from rejecting FPP xenografts
      were transferred to NOD-SCID FPP recipients and tracked by Ly5.1 surface antigen
      or via CSFE staining. Monocyte chemoattractant protein-1 (MCP-1), macrophage
      inflammatory protein-1alpha (MIP-1alpha), macrophage inflammatory protein-1beta
      (MIP-1beta), regulated upon activation, normal T-cell expressed and secreted
      (RANTES), chemokine (C-C motif) receptor 2 (CCR2), chemokine (C-C motif) receptor
      5 (CCR5), toll-like receptors (TLRs) (1-9) and gene expression in transplanted
      FPP xenografts was evaluated by real-time polymerase chain reaction. Gene
      expression of CCR2, CCR5 and TLRs was also analyzed in pooled samples of
      activated and non-activated macrophages. RESULTS: Exogenous macrophages were
      shown to track to and reject recently transplanted but not established FPP
      xenografts. Gene expression for MCP-1, RANTES, MIP-1alpha and MIP-1beta was at
      least 3-fold greater in recently transplanted compared with established
      xenografts (P < 0.05), and CCR2 and CCR5 gene expression was 10-fold greater in
      activated compared non-activated macrophages, suggesting that graft-mediated pro
      inflammatory signals were important for macrophage recruitment. Specific graft
      recognition by macrophages may involve TLR signaling as macrophages exposed to
      porcine islets had higher levels of TLR gene expression compared with those
      exposed to allografts regardless of the level of activation. CONCLUSION:
      Xenografts provide additional activation signals to macrophages that are not seen
      following allotransplantation. This study identifies chemokines and TLR as
      important signals in macrophage-mediated recognition and rejection of islet
      xenografts.

PMID- 17214705
TI  - Influence of strain and age differences on the yields of porcine islet isolation:
      extremely high islet yields from SPF CMS miniature pigs.
AB  - BACKGROUND: Porcine pancreas is a potential source of material for islet
      xenotransplantation. However, the difficulty in isolating islets, because of
      their fragility and the variability of isolation outcome in donor age and breed,
      represents a major obstacle to porcine islet xenotransplantation. In this study,
      we compared the islet isolation yield of specific pathogen-free (SPF) Chicago
      Medical School (CMS) miniature pigs with that of another miniature pig breed and
      market pigs from a local slaughterhouse. METHODS: Nine adult CMS miniature (ACM)
      pigs (>12 months), six young CMS miniature (YCM) pigs (6-7 months), four adult
      Prestige World Genetics (PWG) miniature (APM) pigs (>12 months), and 13 adult
      market (AM) pigs from a local slaughterhouse were used for islet isolation.
      RESULTS: The islet yield per gram of pancreas from ACM pigs (9589 +/- 2823 IEQ/g)
      was significantly higher than that from APM pigs (1752 +/- 874 IEQ/g, P < 0.05),
      AM pigs (1931 +/- 947 IEQ/g, P < 0.05), or YCM pigs (3460 +/- 1985 IEQ/g, P <
      0.05). Isolated islets from ACM pigs were significantly larger than those from AM
      pigs or YCM pigs. The in vitro and in vivo function of isolated islets showed no
      difference among experimental groups. The pancreases of ACM pigs contained higher
      mean islet volume density percentages and larger size of islets than those of AM
      or APM pigs. CONCLUSIONS: We isolated extremely high yields of well-functioning
      islets from ACM pigs bred under SPF conditions. SPF CMS miniature pigs should be
      one of the best porcine islet donors for clinical porcine islet
      xenotransplantation.

PMID- 17214706
TI  - Relation between human decay-accelerating factor (hDAF) expression in pig cells
      and inhibition of human serum anti-pig cytotoxicity: value of highly expressed
      hDAF for xenotransplantation.
AB  - BACKGROUND: Although the successful production of alpha1,3-galactosyltransferase
      knockout (GT-KO) pigs has increased expectations of clinical xenotransplantation,
      additional modifications of genetically engineered pigs are still being explored,
      because even GT-KO pigs are incapable of inhibiting the host's immunological
      response completely. One of the potential candidates is a complement-regulatory
      protein, such as human decay-accelerating factor (hDAF). However, there are few
      reports on how high the expression level of hDAF in pig cells would be required
      for suppression of complement activation. The purpose of this study was to
      examine the relationship between the level of hDAF expression and its inhibitory
      effect on human serum cytotoxicity. METHODS: An expression (pCAGGS) vector
      containing the hDAF gene was transfected into pig fibroblasts using an
      electroporation system (Gene Pulser II). Forty-eight to fifty-two hours after
      transfection, the cells were stained with FITC-labeled anti-hDAF antibody and
      then applied to the cell sorter. hDAF-transfected cells with various expression
      levels were collected by gating on fluorescence intensity. The level of hDAF
      expression was determined relative to that in human control endothelial cells.
      Collected cells expressing x1, x5, x10, x15 and x30 hDAF were incubated into 96
      well plates for 16 h, and the cells were subjected to 3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: hDAF expression
      levels in transfected cells at the time of MTT assay (16 h after sorting) were
      comparable to those immediately after sorting. hDAF expression in pig cells five
      times higher than in human endothelial cells was effective in inhibiting
      complement-dependent cytotoxicity of most human sera. However, 15- to 30-fold
      expression of hDAF was required for effective inhibition of human sera with the
      highest cytotoxic capacity. CONCLUSIONS: A much higher level of hDAF expression
      in pig cells than previously considered necessary might be required to provide
      additional benefit in inhibiting antibody-mediated rejection. Genetically
      engineered pigs that express very high levels of hDAF would be beneficial for
      xenotransplantation.

PMID- 17214707
TI  - Isolation outcome and functional characteristics of young and adult pig
      pancreatic islets for transplantation studies.
AB  - INTRODUCTION: Pig islets have been proposed as an alternative to human islets for
      clinical use, but their use is limited by rejection. The availability of
      genetically modified pigs devoid of alpha1,3-galactosyltransferase might provide
      islets more suitable for xenotransplantation. To limit the costs involved in the
      logistics and health care of pigs for clinical xenotransplantation, we have
      studied whether younger, rather than older, pigs that are typically preferred can
      be used as islet donors. METHODS: We utilized pancreases from Yorkshire and White
      Landrace wild-type pigs and alpha1,3-galactosyltransferase gene-knockout pigs of
      three main different age and size groups: (i) <6 months, (ii) 6 to 12 months, and
      (iii) >2 yr of age, inclusive of retired breeders. We compared isolation yield
      and in vitro and in vivo function of islet cells obtained from these groups.
      RESULTS: Islets from adult pigs (>2 yr) offered not only higher islet yields, but
      retained the ability to preserve intact morphology during the isolation process
      and culture, in association with high functional properties after
      transplantation. Following isolation, islet cells from young (<6 m) and young
      adult (6 to 12 m) pigs dissociated into small aggregates and single cells, and
      exhibited inferior functional properties than adult islets both in vitro and in
      vivo. CONCLUSIONS: These data support the conclusion that, in view of the large
      number of islets needed to maintain normoglycemia after xenotransplantation,
      organ-source pigs need to reach adult age (>2 yr) before being considered optimal
      islet donors, in spite of the higher costs involved.

PMID- 17214708
TI  - Xenotransplantation literature update September-October 2006.

PMID- 17214709
TI  - The Miami results on porcine islet-Sertoli cell xenotransplantation.

PMID- 17214710
TI  - Response to Valdes-Gonzalez ''Clinical trial of islet xenotransplantation in
      Mexico''.

PMID- 17214711
TI  - Evolution of xenoantibodies, after their depletion, in a non-immunosuppressed
      baboon.

PMID- 17214712
TI  - Rene Kuss's clinical experience with pig kidney transplantation in 1966.

PMID- 17214713
TI  - Community-acquired methicillin-resistant Staphylococcus aureus skin infections: a
      review of epidemiology, clinical features, management, and prevention.
AB  - Community-acquired methicillin-resistant Staphylococcus aureus (CAMRSA) infection
      is a global problem of epidemic proportions. Many of the patients who develop
      CAMRSA skin lesions do not have infection-associated risk factors. Abscess,
      abscess with accompanying cellulitis, and cellulitis are the most common
      presentations of cutaneous CAMRSA infection; occasionally, these CARMSA-related
      lesions are misinterpreted as spider or insect bites. Other manifestations of
      cutaneous CAMRSA infection include impetigo, folliculitis, and acute paronychia.
      The management of CAMRSA skin infection includes incision and drainage, systemic
      antimicrobial therapy, and adjuvant topical antibacterial treatment. In addition,
      at the initial visit, bacterial culture of the lesion should be considered.
      Direct skin-to-skin contact, damage to the skin surface, sharing of personal
      items, and a humid environment are potential mechanisms for the acquisition and
      transmission of cutaneous CAMRSA infection. Measures that strive to eliminate
      these causes are useful for preventing the spread of CAMRSA skin infection.

PMID- 17214714
TI  - Topical diclofenac in the treatment of actinic keratoses.

PMID- 17214715
TI  - Mycosis fungoides--a review of the management of 28 patients and of the recent
      literature.
AB  - BACKGROUND: Mycosis fungoides is an uncommon cutaneous T-cell lymphoma
      characterized by malignant monoclonal proliferation of T-helper lymphocytes. Its
      course is variable with a potential for lymphatic and hematogenous involvement.
      We report the investigations, staging, treatment, follow-up, and outcome of 28
      patients. This is the first such study reported from Ireland. METHODS: Twenty
      eight patients with mycosis fungoides (14 women, 14 men; average age, 52.5 years)
      were reviewed over 12 years in the dermatology clinic which assesses an average
      of 4500 patients per year. All mycosis fungoides patients were referred from
      their family physicians. The diagnosis was made in all cases from a combination
      of clinical findings, histology, and immunohistochemistry. TNM staging revealed
      11 patients at diagnosis stage IA (T1), 12 at stage IB (T2), four at stage IIB
      (T3), and one at stage III (T4). RESULTS: The usual male preponderance was not
      found. Eight patients needed multiple biopsies to establish the diagnosis.
      Detailed investigations were not useful in the early stages. Patients were
      followed up over a 12-year period. Thirteen patients died as a result of
      cutaneous lymphoma. Two patients with stage IA disease progressed rapidly and
      died, a feature reported in only 10% of patients at this stage. Five patients
      showed unusual features, including a long history prior to presentation, the
      development of the rarely reported bullous mycosis fungoides, and aggressive
      disease beginning at a young age. CONCLUSIONS: Mycosis fungoides is rare; we
      reviewed 28 patients over 12 years. The prognosis is poor at the later stages; 13
      patients died. Two patients who died were unusual in that they rapidly progressed
      from stage IA disease; however, in the majority of patients with this stage, the
      prognosis is excellent. Detailed investigations were unhelpful in early stage
      disease. Close clinical follow-up is essential to identify disease progression.

PMID- 17214716
TI  - Effect of caffeine and testosterone on the proliferation of human hair follicles
      in vitro.
AB  - BACKGROUND: Androgenetic alopecia (AGA) is a common problem in men of all ages,
      affecting approximately 50% at 50 years of age. The underlying cause is an
      androgen-dependent miniaturization of genetically predetermined hair follicles.
      Here, the hair organ culture model was used to investigate the effects of
      testosterone and caffeine; the latter being a promising candidate for hair growth
      stimulation. METHODS: Hair follicles from 14 biopsies, taken from the vertex
      areas from male AGA patients, were cultivated for 120-192 h in vitro with normal
      William's E medium (control) or William's E medium containing different
      concentrations of testosterone and/or caffeine. Hair shaft elongation was
      measured daily and at the end of cultivation, cryosections of follicles were
      stained with Ki-67 to evaluate the degree and localization of keratinocyte
      proliferation. RESULTS: Significant growth suppression was found in hair
      follicles treated with 5 microg/ml testosterone. This was counteracted by
      caffeine in concentrations of 0.001% and 0.005%. Moreover, caffeine alone led to
      a significant stimulation of hair follicle growth. These results were confirmed
      immunohistochemically by Ki-67 staining. CONCLUSIONS: Androgen-dependent growth
      inhibition of ex vivo hair follicles from patients suffering from AGA was present
      in the human hair organ culture model, a constellation which may serve for future
      studies to screen new substances against androgen-dependent hair loss. Caffeine
      was identified as a stimulator of human hair growth in vitro; a fact which may
      have important clinical impact in the management of AGA.

PMID- 17214717
TI  - Clinical study with allogeneic cultured dermal substitutes for chronic leg
      ulcers.
AB  - BACKGROUND: Clinical studies of the use of allogeneic cultured dermal substitutes
      (CDSs) have been conducted in 30 medical centers across Japan with the support of
      the Millennium Project of the Ministry of Health, Labor and Welfare. The CDS is
      prepared by plating cultured fibroblasts on a spongy matrix made from hyaluronic
      acid and atelo-collagen. The aim of the present clinical study was to evaluate an
      allogeneic CDS as cell therapy in which cytokines are released to promote wound
      healing. MATERIALS AND METHODS: The CDS was applied repeatedly at an interval of
      5-7 days to 13 patients being treated with intractable chronic leg ulcers, using
      the CDS as a dermatological treatment. Intractable leg ulcers, whether venous or
      arterial, are difficult to heal because they occur as a secondary change of
      disease. RESULTS: None of these patients had responded to conventional therapies
      such as topical or surgical methods, but 77% of the patients had an efficacy
      score of > 80 points for wound healing with allogeneic CDS. A high safety level
      was obtained: A, 84.6%; B and C, 7.7%; D, 0%. In 92% of the patients, the final
      assessment of wound healing was good or very good. CONCLUSIONS: For promotion of
      wound healing, the present CDS is superior to existing topical agents and
      occlusive dressings.

PMID- 17214718
TI  - Basal cell carcinoma in outdoor versus indoor workers in Turkey.
AB  - BACKGROUND: Basal cell carcinoma remains a significant health problem, and is
      most common in people of Caucasian origin with significant sun exposure. This
      study investigated differences between two groups of Turkish patients with basal
      cell carcinoma: indoor workers versus outdoor workers. METHODS: One hundred and
      twenty-one patients with primary basal cell carcinoma were categorized as outdoor
      (Group OW) or indoor workers (Group IW), according to sun exposure at work.
      Findings for age, sex, skin type, tumor location, and histologic
      subtype/aggression were compared. RESULTS: The mean age of Group IW was lower
      than that of Group OW (57.3 +/- 9.2 vs. 65.8 +/- 12.2 years, respectively). Group
      OW comprised more men than women (63.4% vs. 36.6%, respectively), whereas women
      predominated in Group IW (62% vs. 38%, respectively). The facial cheek was a more
      frequent tumor site in Group IW than in Group OW (20% vs. 7.0%, respectively).
      There were no statistical differences with respect to skin types or histological
      subtypes; however, Group OW had a higher proportion of aggressive subtypes than
      Group IW (25.4% vs. 10%, respectively). CONCLUSIONS: The results in the Turkish
      population of the study suggest that basal cell carcinoma may develop in indoor
      workers (intermittent sun exposure) earlier than in outdoor workers with chronic
      sun-exposure, but more aggressive subtypes are more likely to be linked with
      chronic sun-exposure.

PMID- 17214719
TI  - Vitiligo prevalence study in Shaanxi Province, China.
AB  - BACKGROUND: Recent publications, especially those based on population surveys,
      show that the presumed vitiligo prevalence of 1-2% is overestimated. OBJECTIVE:
      To obtain the vitiligo prevalence in Shaanxi Province, China, through a
      population survey. METHODS: Approximately one-thousandth of the 36.05 million
      people in Shaanxi Province, China, were selected through stratified four-stage
      cluster sampling. They lived in 180 investigation units and all were investigated
      in a door-to-door survey. Vitiligo and suspected vitiligo patients were marked in
      the basic questionnaire. They were encouraged to complete a well-prepared
      questionnaire and send it back to the investigation center. The questionnaire
      assigned to the investigators contained questions about vitiligo characteristics,
      such as the area affected, number of areas, and whether or not the affected areas
      were covered by scurf. Professional dermatologists verified these results.
      RESULTS: There were 42,833 people in 180 investigation units. The sex, residence,
      and educational level of these individuals were representative of the population
      of Shaanxi Province. The investigation team reported 43 vitiligo patients and 14
      with suspected vitiligo. During the verification period, three patients and all
      those with suspected vitiligo were excluded. In total, there were 40 patients (17
      women and 23 men). Eleven lived in urban areas and 29 in rural areas.
      CONCLUSIONS: The prevalence of vitiligo in Shaanxi Province is 0.093% (95%
      confidence interval, 0.067-0.127%). No significant difference was found between
      males and females or between urban and rural residents.

PMID- 17214720
TI  - Myiasis owing to Dermatobia hominis in a HIV-infected subject: Treatment by
      topical ivermectin.
AB  - We report the occurrence of myiasis owing to Dermatobia hominis (Dh) in a HIV
      infected subject. HIV infection did not modify the pathogenicity of myiasis.
      However, the clinical presentation seemed unusual with voluminous inflammatory
      nodules. Use of topical ivermectin killed the larvae and facilitated their
      extraction.

PMID- 17214721
TI  - Cutaneous anthrax in a remote tribal area--Araku Valley, Visakhapatnam district,
      Andhra Pradesh, southern India.

PMID- 17214722
TI  - Neutrophilic eccrine hidradenitis in non-small cell lung cancer.
AB  - A 75-year-old man was treated for non-small cell lung cancer (NSCLC) (stage IIIb)
      with three-cycle chemotherapy (cisplatin and paclitaxel) for 3 weeks. No skin
      lesions were observed during the first and second chemotherapy cycles. After the
      third chemotherapy cycle, he developed slightly pruritic skin eruptions on the
      anterior chest. He was treated for 1 month with topical steroid without
      improvement, and was referred to our dermatologic department. Skin examination
      revealed slightly elevated, dusky, erythematous, edematous patches on the
      anterior chest in a bilateral distribution (Fig. 1). Histologic examination of a
      biopsy specimen taken from the cutaneous lesions showed a neutrophilic infiltrate
      surrounding the secretory eccrine glands. The epithelial cells of the eccrine
      ducts and coils were not affected. There was a mild superficial perivascular
      infiltrate of mainly lymphocytes. These changes were consistent with a diagnosis
      of neutrophilic eccrine hidradenitis (Fig. 2). He was treated with dapsone, 50
      mg/day, and methylprednisolone, 8 mg/day, for 2 weeks, and his skin lesions
      improved. Two months later the erythematous eruptions recurred on the chest,
      back, and extremities without the use of any chemotherapeutic agent, and were
      treated effectively with the same drugs.

PMID- 17214723
TI  - Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES).
AB  - Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare inherited
      condition that includes characteristic eyelid malformations and sometimes reduced
      fertility in females. Genetic studies have implicated mutations in the forkhead
      transcription factor FOXL2 as responsible for BPES. We report a female and her
      father with BPES type I, who presented the 1092-1108dup17 mutation in the FOXL2
      gene. Molecular studies and the typical clinical features of BPES should allow
      the dermatologist to reach an early diagnosis and permit the treatment of eyelid
      alterations and the investigation of infertility.

PMID- 17214724
TI  - Novel mutations in two families with Darier's disease.
AB  - BACKGROUND: Darier's disease (DD) is an autosomal dominant skin disorder
      characterized by abnormal keratinization and acantholysis. Deleterious mutations
      in the gene ATP2A2 which encodes SERCA2, a calcium pump of the sarco/endoplasmic
      reticulum underlie the disease. OBJECTIVE: To identify the genetic defect in two
      Jewish families of eastern-European ancestry with DD. METHODS: DNA was extracted
      from peripheral blood of six patients and three healthy members of the two
      families. Polymerase chain reaction (PCR) was carried out to amplify the exons
      and flanking intron boundaries of the ATP2A2 gene followed by direct sequencing.
      Restriction fragment analysis verified the presence or absence of the mutations.
      Results Two novel mutations were identified. A nonsense mutation, a change of
      C391 to T (R131X) in exon 5, was found in one family and a missense mutation, a
      change of A530 to C (Q177P) in the second. The mutations were not present in 50
      healthy individuals of the same ethnic origin. Both pathogenic mutations are in
      codons that are located in a highly conserved cytoplasmic beta-strand domain
      which functions as the transduction site. CONCLUSION: The existence of two
      mutations in two Jewish families of the same ancestry might confirm the
      previously published reports that most mutations in that gene are private.

PMID- 17214725
TI  - Cutaneous and pulmonary sarcoidosis in a patient with HIV after highly active
      antiretroviral therapy.

PMID- 17214726
TI  - Cutaneous manifestations of Costello syndrome.
AB  - Cutaneous findings are common in Costello syndrome, but have not been extensively
      reviewed in the dermatology literature. We present the cutaneous and
      histopathologic findings from two cases of Costello syndrome and review
      previously described cutaneous features of this syndrome. Both patients had
      manifestations of Costello syndrome with thick, lax skin on the dorsal aspects of
      hands and feet, deep palmar and plantar creases, curly hair, hyperkeratoses,
      acanthosis nigricans, papillomas, and multiple pigmented lesions. One patient had
      multiple syringomas on the forearms, a finding not previously reported. Pigmented
      lesions have previously been reported as nevi in the literature though no
      biopsies have been reported. We conclude that thick, loose skin on the dorsal
      aspects of hands and feet and deep palmar and plantar creases are cardinal
      manifestations of Costello syndrome and benign tumors of ectodermal origin such
      as papillomas, calcified epitheliomas, dermoid cysts, mammary fibroadenosis, and
      syringomas are important features of this syndrome.

PMID- 17214727
TI  - Multiple keratoacanthomas in a young woman: report of a case emphasizing medical
      management and a review of the spectrum of multiple keratoacanthomas.
AB  - A 27-year-old white woman was referred for consultation with regard to the
      presence of extensive multiple keratotic lesions. She began to develop these
      lesions at the age of 9 years, with healing of the lesions resulting in scar
      formation. A biopsy was performed at the age of 16 years, but the patient was
      unsure of the results. Since then, she had not had any treatment or biopsies, and
      stated that she had not suffered from any health problems during the intervening
      period. She was most concerned about the tumors on her heels and soles, which
      caused difficulty with ambulation. The family history was negative for skin
      diseases, including melanoma, nonmelanoma skin cancer, psoriasis, and eczema, and
      positive for Type II diabetes mellitus. A relative reported that the patient's
      grandfather had similar lesions, but the patient's parents and siblings were
      healthy. She was married and had one child, a 9-year-old daughter. Her child had
      no skin lesions. The patient's only medication was Ortho-Tricyclene birth control
      pills. She had no known drug allergies. Physical examination revealed the
      presence of multiple lesions on her body (Fig. 1). Her left superior helix
      contained a well-demarcated, dome-shaped nodule with a rolled, mildly
      erythematous border with a central hyperkeratotic plug. A similar lesion was
      present in the scaphoid fossa of the left ear and smaller lesions were scattered
      on her face. Numerous lesions were present on the arms and legs bilaterally, with
      the majority of lesions being located on the anterior lower legs. There were also
      lesions present on the palms and soles. The lesions ranged in size from 5 mm to 3
      cm, the largest being a verrucous exophytic nodule on the anterior aspect of her
      left leg. Overall, there appeared to be two distinct types of lesion. One type
      appeared round, oval, and symmetric with a central keratotic plug, similar to
      that on the ear. The other type was larger, more exophytic, and verrucous,
      including the lesions on the volar surfaces. Also present were numerous,
      irregularly shaped atrophic scars where previous lesions had healed
      spontaneously. There were no oral lesions or lesions on her fingernails or
      toenails, and her teeth and hair were normal. A biopsy was obtained from an early
      lesion on the right dorsal forearm. Histology revealed an exo-/endophytic growth
      having a central crater containing keratinous material (Fig. 2). The crater was
      surrounded by markedly hyperplastic squamous epithelium with large squamous
      epithelial cells having abundant glassy cytoplasm. Some cells were dyskeratotic.
      Within the dermis was a dense, chiefly mononuclear inflammatory infiltrate. A
      buttress of epidermis surrounded the crater. The clinical and pathologic data
      were consistent with keratoacanthomas. Initial laboratory screenings revealed
      elevated triglycerides and total cholesterol, 537 mg/dL (normal, < 150 mg/dL) and
      225 mg/dL (normal, < 200 mg/dL), respectively, with all other laboratory results
      within normal limits. In anticipation of starting oral retinoid therapy for her
      multiple keratoacanthomas, she was referred to her primary care physician for
      control of hyperlipidemia. After her lipids had been controlled, she was placed
      on isotretinoin (Accutane) 40 mg/day. There was some interval improvement with
      regression of some lesions leaving atrophic scars. She was also started on
      topical application of tazarotene (Tazorac) for all nonresolving lesions.
      Possible side-effects from the isotretinoin occurred, including dry mouth and
      eyes. After 8 months of isotretinoin, the patient was switched to acitretin
      (Soriatane) 25 mg to determine whether it might have a more beneficial effect on
      the resistant lesions. Many of the larger lesions regressed leaving atrophic
      scars. The dose of acitretin was subsequently increased to 35 mg because the
      lesions on her heel and the ball of her foot persisted. Almost all of the lesions
      resolved, except those on her feet, which are slowly regressing. Currently, the
      patient is on a regimen of acitretin 25 mg once a day with tazarotene 0.1% gel
      applied directly to the few residual keratoacanthomas on her feet, which are
      slowly improving.

PMID- 17214728
TI  - Laser treatment of keloids and hypertrophic scars.
AB  - BACKGROUND: Lasers have been used in the treatment of hypertrophic scars and
      keloids for more than 20 years. Different laser systems have been examined; among
      them pulsed dye lasers are currently considered the laser of choice in these
      settings. OBJECTIVES: The purpose of this study is to review the pertinent
      literature and provide updated information on different laser therapies available
      for treatment of keloids and hypertrophic scars. METHODS: A Medline literature
      search was performed for relevant publications. RESULTS: In this review the
      results of published studies in the treatment and prevention of hypertrophic
      scars and keloids are presented. Suggested mechanisms of action are reviewed. A
      review of the optimal laser parameters to modulate treatment outcome will be
      discussed. Different lasers are effective in not only the treatment but also the
      prevention of hypertrophic scars and keloids, among them PDL is more promising.
      Most of the suggested theories are based on the selective photothermolysis in
      which the light energy emitted from a vascular laser is absorbed by hemoglobin,
      generating heat and leading to coagulation necrosis, neocollagenesis, collagen
      fiber heating with dissociation of disulfide bonds and subsequent collagen fiber
      realignment. CONCLUSION: The optimal laser is currently 585 nm PDL, although the
      recent results of Q-switched 532 nm frequency-doubled Nd:YAG are promising. Early
      use of lasers are beneficial, especially in those who are prone to develop these
      lesions.

PMID- 17214729
TI  - Treatment of acne vulgaris without antibiotics: tertiary amine-benzoyl peroxide
      combination vs. benzoyl peroxide alone (Proactiv Solution).
AB  - BACKGROUND: Concerns have arisen over the development of antibiotic-resistant
      organisms due to the prolonged use of oral and topical antibiotics in acne
      vulgaris. We have previously demonstrated that benzoyl peroxide used in consort
      with a chemical with an accessible tertiary amine, such as an allylamine,
      increases radical activity and biological effect. OBJECTIVES: The purpose of this
      pilot study was to assess the efficacy of two nonantibiotic topical remedies for
      mild to moderate acne, with one of the agents being a combination of benzoyl
      peroxide with butenifine, an allylamine. METHODS: In an open-label, patient
      satisfaction, 8-week comparative study, 23 patients demonstrating mild to
      moderate facial acne were given randomly either benzoyl peroxide in Proactiv
      Solution or the combination of benzoyl peroxide with an allylamine. RESULTS: The
      allylamine-benzoyl peroxide combination therapy outperformed Proactiv Solution
      during each 2-week stage of evaluation in terms of reduction of comedones,
      inflammatory lesions, and degree of oiliness. There was a marked preference for
      the allylamine-benzoyl peroxide combination in terms of patient satisfaction.
      CONCLUSIONS: Benzoyl peroxide used in consort with antimicrobial agents that
      contain an accessible tertiary amine, such as erythromycin, has previously been
      shown to increase radical activity and biological effect. Trials of short
      duration with small numbers of patients do not adequately inform practitioners
      about whether the combination of allylamines with benzoyl peroxide is a viable
      alternative to topical antibiotic therapy for acne. Nevertheless, the higher
      satisfaction with the allylamine-benzoyl peroxide combination certainly warrants
      further investigation.

PMID- 17214730
TI  - Randomized, double-blind clinical evaluation of the efficacy and safety of
      topical eflornithine HCl 13.9% cream in the treatment of women with facial hair.

PMID- 17214731
TI  - Juvenile mycosis fungoides treated with bexarotene and PUVA.
AB  - A 14-year-old Caucasian boy presented with a 4-month history of a slightly
      pruritic eruption that began on the hips and later extended to the trunk and
      upper and lower limbs. The patient did not present fever, weight loss, or
      asthenia. Physical examination revealed multiple, red, desquamative, oval patches
      with areas of healthy skin between them, which covered nearly 50% of the body
      surface area. The palms, soles, face, and mucosa were not affected. In addition,
      he presented two violet-colored infiltrated plaques on the left thigh and right
      buttock (Fig. 1). There were multiple, > 1 cm, freely mobile, axillary and
      inguinal nodes. In follow-up, the patient developed two red-colored, mobile, well
      delimited cutaneous nodules of 2.5 cm in diameter in the right hemithorax and
      lumbar area. The lumbar nodule regressed spontaneously before treatment. The
      clinical diagnosis was mycosis fungoides. We obtained three skin biopsies, one
      from a patch lesion and the others from a nodule; the third was sent to a
      reference hospital to determine the rearrangement. Histologic examination was
      similar in the three biopsies and revealed an atypical lymphoid infiltrate in the
      superficial dermis with epidermotropism and a tumoral nodule of atypical, small
      sized lymphocytes in the deep dermis and subcutaneous level (Fig. 2). The
      atypical infiltrate was CD3+, CD4+, CD8-, T-cell intracellular antigen (TIA)+/-,
      Epstein-Barr-encoded RNA (EBER)-, and CD56-. The biopsy of one left axillary
      adenopathy was compatible with mycosis fungoides (Fig. 3). Amongst the additional
      tests carried out was a blood analysis showing 5300 leukocytes (neutrophils, 35%;
      lymphocytes, 40.7%; monocytes, 16.8%; eosinophils, 6.40%) without Sezary cells,
      normal lactate dehydrogenase (LDH), immunoglobulin E (IgE) of 497 U/mL (normal, 3
      100 U/mL), and beta2-microglobulin of 3.09 mg/L (normal, 1.64 +/- 0.58 mg/L). A
      bone marrow study and a thoraco-abdomino-pelvic scan were normal. The
      rearrangement in the skin was monoclonal, whereas in peripheral blood and lymph
      nodes it was polyclonal. With the diagnosis of mycosis fungoides stage IVA
      (according to the TNM classification), treatment was initiated with psoralen plus
      ultraviolet light A (PUVA), three times a week, plus oral bexarotene at a dose of
      300 mg/m2/day. The parents were informed that this treatment was not approved for
      this age group and informed consent was obtained. The clinical tolerance to
      bexarotene was very good, although low doses of atorvastatin (10 mg/day) and 75
      100 mg of thyroxine were needed to control the expected adverse reactions to oral
      retinoid. After 32 sessions of PUVA and 6 months of treatment with oral
      bexarotene, the skin patches regressed, except for the plaque on the left buttock
      and the nodule on the right hemithorax (Fig. 4). There was no evidence of
      lymphadenopathy clinically or via sonographic evaluation. Bexarotene was
      discontinued after patient clearance and resolution of adenopathies.
      Nevertheless, 5 months after discontinuation of oral treatment, the patient
      developed multiple, scaling, nonconfluent macules on the trunk and arms affecting
      almost 30% of the body surface area, which disappeared with the application of
      methylprednisolone aceponate. He did not present significant lymphadenopathies.

PMID- 17214732
TI  - From genesis to gene sequencing: historical progress in the understanding of skin
      color.
AB  - Since at least biblical times, humans have pondered on why there might be
      variation in skin color and what might constitute the nature of that difference.
      In this article, two historical trails are followed, one beginning with the
      Ancient Greeks, the other with the Ancient Chinese. These two paths converge to
      provide us with some historical evidence to back recent scientific discoveries in
      the dynamic regulation of skin pigmentation, focusing on melanocyte-stimulating
      hormone and its natural antagonist agouti-signaling protein.

PMID- 17214733
TI  - Neutrophilic dermatoses occurring in oncology patients.

PMID- 17214734
TI  - Acute effects of periodontal therapy on bio-markers of vascular health.
AB  - AIM: We aimed to study the impact of periodontal therapy on several bio-markers
      related to vascular health. MATERIAL AND METHODS: Fifty-five consecutive subjects
      (age range 30-64 years) having severe periodontitis received an intensive session
      of periodontal therapy under local anaesthesia and provided blood samples before
      and 1 and 7 and 30 days following therapy. High-sensitivity assays were utilized
      to quantify serum concentrations of inflammatory markers [interleukin (IL)-1beta,
      tumour necrosis factor-alpha], plasma haemostatic (D-dimer) and endothelial
      soluble markers [soluble E-selectin (s-Es) and von Willebrand factor antigen (r
      WF:Ag)]. RESULTS: Periodontal therapy elicited a significant activation of the
      haemostatic system (38% and 68% mean increases of plasma D-dimer 1 and 7 days
      after therapy, respectively, p<0.001), together with moderate endothelial
      dysfunction (10% and 30% mean increases at 24 h in plasma soluble E-selectin,
      p<0.05 and von-Willebrand factor, p<0.01, respectively). D-Dimer and s-Es acute
      changes were significantly correlated with periodontal treatment time (p<0.05).
      Cigarette smoking status and body mass index strongly influenced the acute
      release of IL-1beta (p<0.05), D-dimer (p<0.01) and s-Es (p<0.01). CONCLUSIONS:
      Periodontal therapy represents a novel and reliable non-drug-induced model to
      investigate in vivo the interplay between inflammation, coagulation and
      endothelial cell activation.

PMID- 17214735
TI  - Distribution and diversity of tetracycline resistance genes encoding ribosomal
      protection proteins in Mekong river sediments in Vietnam.
AB  - We investigated the distribution and diversity of tetracycline resistance genes
      encoding ribosomal protection proteins (RPPs) in river and channel sediments of
      the Mekong Delta in Vietnam. The sediment samples were taken from nine sites in
      the Hau River in southern Vietnam and from 1 site in a channel in Can Tho City in
      May 2004 using an Ekman-Birge sediment surface sampler. The RPP genes were
      amplified using PCR with DNA templates obtained directly from the sediments. The
      tet(M), tet(S), and tet(W) genes were detected by PCR in most sediment samples.
      Denaturing gradient gel electrophoresis analysis of these genes and sequencing of
      the resulting bands showed that tet(S) and tet(W) had only one genotype each, but
      that tet(M) had at least two, which were tentatively called type 1 and type 2.
      Type 1 tet(M) was identical to the gene encoded in various plasmids and
      transposons of gram-positive and gram-negative bacteria, and type 2tet(M) was
      similar to the gene encoded in Tn1545 of Enterococcus faecalis (99% identity, 170
      bp/171 bp). This study showed that various RPP genes were widely distributed in
      the river and channel sediments of the Mekong Delta.

PMID- 17214736
TI  - Glucan-binding proteins are essential for shaping Streptococcus mutans biofilm
      architecture.
AB  - Glucan plays a central role in sucrose-dependent biofilm formation by the dental
      pathogen Streptococcus mutans. This organism synthesizes several proteins capable
      of binding glucan. These are divided into the glucosyltransferases that catalyze
      the synthesis of glucan and the nonglucosyltransferase glucan-binding proteins
      (Gbps). The biological significance of the Gbps has not been thoroughly defined,
      but studies suggest that these proteins influence virulence and play a role in
      maintaining biofilm architecture by linking bacteria and extracellular molecules
      of glucan. We engineered a panel of Gbp mutants, targeting GbpA, GbpC, and GbpD,
      in which each gene encoding a Gbp was deleted individually and in combination.
      These strains were then analyzed by confocal microscopy and the biofilm
      properties were quantified by the biofilm quantification software comstat. All
      biofilms produced by mutant strains lost significant depth, but the basis for the
      reduction in height depended on which particular Gbp was missing. The loss of the
      cell-bound GbpC appeared dominant as might be expected based on losing the
      principal receptor for glucan. The loss of an extracellular Gbp, either GbpA or
      GbpD, also profoundly changed the biofilm architecture, each in a unique manner.

PMID- 17214737
TI  - Compromised GCF total antioxidant capacity in periodontitis: cause or effect?
AB  - BACKGROUND: Oxidative stress is implicated in the pathogenesis of periodontitis.
      The total antioxidant capacity (TAOC) of gingival crevicular fluid volume (GCF)
      and plasma appears compromised in periodontitis, but it is unclear whether this
      predisposes to, or results from the inflammatory process. AIM: To investigate
      longitudinal changes in GCF and plasma TAOC following reductions in periodontal
      inflammation with successful non-surgical therapy. MATERIALS AND METHODS: Two
      longitudinal studies were run in series on non-smokers with chronic periodontitis
      (CP). Study-1 (n=17) assessed index sites with mild disease; Study-2 (n=18)
      investigated deep sites. GCF sampling and clinical measures were performed at
      baseline and 3 months post-therapy. Plasma and GCF TAOC was determined by
      enhanced chemiluminescence and 32 age/sex-matched periodontally healthy controls
      were used. RESULTS: Therapy improved clinical outcomes consistent with the
      literature. There were no differences in plasma TAOC between periodontitis
      patients (507+/-92 microMTeq) and controls (520+/-100 microMTeq; p=0.57) at
      baseline, but GCF TAOC was lower (p<0.0001) in CP patients (680+/-371 microMTeq)
      than controls (1129+/-722 microMTeq). Successful periodontal therapy did not
      alter plasma TAOC (p=0.56), but GCF TAOC increased (by 449+/-722 microMTeq,
      p<0.001) to control subject levels (p=0.47) CONCLUSIONS: Local total antioxidant
      capacity in CP appears to reflect increased oxygen radical activity during
      periodontal inflammation and can be restored to control subject levels by
      successful non-surgical therapy.

PMID- 17214738
TI  - Acute monocytic leukaemia with histiocytic features.

PMID- 17214739
TI  - An update on the management of severe idiopathic aplastic anaemia in children.
AB  - The current outlook for a child with severe idiopathic aplastic anaemia (AA) is
      very much better than in previous decades. In part, this may reflect better
      differentiation of idiopathic and inherited marrow failure. For children with
      idiopathic AA and a human leucocyte antigen (HLA)-matched sibling donor (MSD),
      allogeneic haematopoietic stem-cell transplantation (AHSCT) is the primary
      therapy of choice, offering long-term disease-free survival of 90%, although
      graft-versus-host disease remains a cause of long-term morbidity. A greater
      treatment challenge remains for those children without a MSD. Combination
      immunosuppressive therapy (IST) is associated with response rates of 70% or more.
      However, relapse and clonal evolution with transformation to myelodysplasia or
      acute myeloid leukaemia remain significant problems after IST and long-term event
      free survival rates are less impressive. For children who do not have a sustained
      response to IST, alternate donor AHSCT should be considered. New HLA typing
      technologies, novel stem cell sources, reduced-intensity conditioning and graft
      engineering have reduced toxicity and improved the outcome after alternate donor
      AHSCT. Emerging therapies that capitalise on recent advances in our understanding
      of the pathophysiology of idiopathic AA and the immunobiology of AHSCT and IST
      may further improve the long-term outcome of this disease.

PMID- 17214740
TI  - A sirtuin in the African trypanosome is involved in both DNA repair and telomeric
      gene silencing but is not required for antigenic variation.
AB  - Silent information regulator 2 (Sir2)-related proteins or sirtuins function as
      NAD(+)-dependent deacetylases or ADP ribosylases that target a range of
      substrates, thereby influencing chromatin structure and a diverse range of other
      biological functions. Genes encoding three Sir2-related proteins (SIR2rp1-3) have
      been identified in the parasitic trypanosomatids, early branching protozoa with
      no previously reported transcriptional silencing machinery. Here we show that, in
      the mammalian-infective bloodstream-stage of the African trypanosome, Trypanosoma
      brucei, SIR2rp1 localizes to the nucleus while SIR2rp2 and SIR2rp3 are both
      mitochondrial proteins. The nuclear protein, SIR2rp1, controls DNA repair and
      repression of RNA polymerase I-mediated expression immediately adjacent to
      telomeres. Antigenic variation, however, which involves the silencing and Pol I
      mediated transcriptional switching of subtelomeric variant surface glycoprotein
      genes, continues to operate independent of SIR2rp1.

PMID- 17214741
TI  - Reconstitution of the Escherichia coli macrolide transporter: the periplasmic
      membrane fusion protein MacA stimulates the ATPase activity of MacB.
AB  - Periplasmic membrane fusion proteins (MFPs) are essential components of the type
      I protein secretion systems and drug efflux pumps in Gram-negative bacteria.
      Previous studies suggested that MFPs connect the inner and outer membrane
      components of the transport systems and by this means co-ordinate the transfer of
      substrates across the two membranes. In this study, we purified and reconstituted
      the macrolide transporter MacAB from Escherichia coli. Here, MacA is a
      periplasmic MFP and MacB is an ABC-type transporter. Similar to other MFP
      dependent transporters from E. coli, the in vivo function of MacAB requires the
      outer membrane channel TolC. The purified MacB displayed a basal ATPase activity
      in detergent micelles. This activity conformed to Michaelis-Menten kinetics but
      was unresponsive to substrates or accessory proteins. Upon reconstitution into
      proteoliposomes, the ATPase activity of MacB was strictly dependent on MacA. The
      catalytic efficiency of MacAB ATPase was more than 45-fold higher than the
      activity of MacB alone. Both the N- and C-terminal regions of MacA were essential
      for this activity. MacA stimulated MacB ATPase only in phospholipid bilayers and
      did not need the presence of macrolides. Our results suggest that MacA is a
      functional subunit of the MacB transporter.

PMID- 17214742
TI  - A highly conserved MAPK-docking site in Mst7 is essential for Pmk1 activation in
      Magnaporthe grisea.
AB  - In Magnaporthe grisea, the MST11-MST7-PMK1 MAP kinase (MAPK) cascade is essential
      for appressorium formation and plant infection. Although expressing a dominant
      active MST7 allele results in Pmk1 activation in the absence of Mst11 and
      improper regulation of appressorium formation, the direct interaction between
      Mst7 and Pmk1 is not observed in yeast two-hybrid assays. Thus, it is not clear
      how Mst7 transmits the upstream signals to Pmk1. Like its homologues from other
      ascomycetes, Mst7 contains a putative MAPK-docking site (12-20) at its N
      terminus. Deletion of this MAPK-docking site had no obvious effect on the
      expression of MST7 but blocked appressorium formation and plant infection. The
      kinase activity of Mst7 was not affected by the docking site deletion but
      Mst7(Delta12-20) failed to activate Pmk1. Mutations in the putative docking
      region of Pmk1 also abolished appressorium formation. In both co
      immunoprecipitation and bimolecular fluorescence complementation (BiFC) assays,
      the direct interaction between Mst7 and Pmk1 was detected only during
      appressorium formation. Deletion of the MAPK-docking site of Mst7 eliminated the
      Mst7-Pmk1 interaction in M. grisea. These data indicate that the MAPK-docking
      site of Mst7 is essential for its association and activation of downstream Pmk1,
      and the Mst7-Pmk1 interaction is enhanced or stabilized during appressorium
      formation.

PMID- 17214743
TI  - Shigella chromosomal IpaH proteins are secreted via the type III secretion system
      and act as effectors.
AB  - Shigella possess 220 kb plasmid, and the major virulence determinants, called
      effectors, and the type III secretion system (TTSS) are exclusively encoded by
      the plasmid. The genome sequences of S. flexneri strains indicate that several
      ipaH family genes are located on both the plasmid and the chromosome, but whether
      their chromosomal IpaH cognates can be secreted from Shigella remains unknown.
      Here we report that S. flexneri strain, YSH6000 encodes seven ipaH cognate genes
      on the chromosome and that the IpaH proteins are secreted via the TTSS. The
      secretion kinetics of IpaH proteins by bacteria, however, showed delay compared
      with those of IpaB, IpaC and IpaD. Expression of the each mRNA of ipaH in
      Shigella was increased after bacterial entry into epithelial cells, and the IpaH
      proteins were secreted by intracellular bacteria. Although individual chromosomal
      ipaH deletion mutants showed no appreciable changes in the pathogenesis in a
      mouse pulmonary infection model, the DeltaipaH-null mutant, whose chromosome
      lacks all ipaH genes, was attenuated to mice lethality. Indeed, the histological
      examination for mouse lungs infected with the DeltaipaH-null showed a greater
      inflammatory response than induced by wild-type Shigella, suggesting that the
      chromosomal IpaH proteins act synergistically as effectors to modulate the host
      inflammatory responses.

PMID- 17214744
TI  - Amrubicin, a novel 9-aminoanthracycline, enhances the antitumor activity of
      chemotherapeutic agents against human cancer cells in vitro and in vivo.
AB  - Amrubicin, a completely synthetic 9-aminoanthracycline derivative, is an active
      agent in the treatment of untreated extensive disease-small-cell lung cancer and
      advanced non-small-cell lung cancer. Amrubicin administered intravenously at 25
      mg/kg substantially prevented the growth of five of six human lung cancer
      xenografts established in athymic nude mice, confirming that amrubicin as a
      single agent was active in human lung tumors. To survey which antitumor agent
      available for clinical use produces a synergistic interaction with amrubicin, we
      examined the effects in combinations with amrubicinol, an active metabolite of
      amrubicin, of several chemotherapeutic agents in vitro using five human cancer
      cell lines using the combination index (CI) method of Chou and Talalay.
      Synergistic effects were obtained on the simultaneous use of amrubicinol with
      cisplatin, irinotecan, gefitinib and trastuzumab, with CI values after 3 days of
      exposure being <1. Additive effect was observed with the combination containing
      vinorelbine with CI values indistinguishable from 1, while the combination of
      amrubicinol with gemcitabine was antagonistic. All combinations tested in vivo
      were well tolerated. The combinations of cisplatin, irinotecan, vinorelbine,
      trastuzumab, tegafur/uracil, and to a lesser extent, gemcitabine with amrubicin
      caused significant growth inhibition of human tumor xenografts without
      pronouncedly enhancing body weight loss, compared with treatment using amrubicin
      alone at the maximum tolerated dose. Growth inhibition of tumors by gefitinib was
      not antagonized by amrubicin. These results suggest that amrubicin appears to be
      a possible candidate for combined use with cisplatin, irinotecan, vinorelbine,
      gemcitabine, tegafur/uracil or trastuzumab.

PMID- 17214745
TI  - Overexpression of soluble vascular endothelial growth factor receptor 1 in
      colorectal cancer: Association with progression and prognosis.
AB  - We examined the expression of sVEGFR1 in colorectal cancer tissue and
      corresponding normal colorectal mucosa to assess the clinical significance of
      sVEGFR1 in colorectal cancer. We also assessed the relationship between sVEGFR1
      levels and various clinicopathologic factors and prognoses. sVEGFR1 and VEGF
      levels were measured in fresh-frozen tumor extracts from 84 primary colorectal
      cancer tissues and 27 corresponding normal mucosa using ELISA. Mean of sVEGFR1
      levels were 3.17 ng/mg protein. sVEGFR1 levels increased significantly in cancer
      tissue compared with normal mucosa. Although VEGF levels increased in cancer
      tissues, the ratio of sVEGFR1/VEGF in cancer tissue was significantly lower than
      that in normal tissue. No significant correlation between sVEGFR1 or VEGF levels
      and any clinicopathologic parameter was found. Overexpression of sVEGFR1 was
      significantly associated with a favorable prognosis. Based on sVEGFR1 levels in
      colorectal cancer without distant metastases, patients with higher sVEGFR1 levels
      (>=1.5 ng/mg protein) demonstrated significant longer recurrence-free survival
      than patients with lower sVEGFR1 levels (<1.5 ng/mg protein) (P = 0.0017).
      Multivariate analysis showed that the sVEGFR1 levels in cancer tissue were an
      independent prognostic indicator of disease progression. sVEGFR1 expression was
      significantly elevated in colorectal cancer tissue compared with normal mucosa
      and the intratumoral balance between sVEGFR1 and VEGF was significantly different
      between tumor tissue and normal controls. Furthermore, sVEGFR1 levels showed a
      significant prognostic value. Further studies concerning the biologic and
      therapeutic significance of sVEGFR1 in colorectal cancer are warranted.

PMID- 17214746
TI  - Transforming growth factor-[beta]1 -509T reduces risk of colorectal cancer, but
      not adenoma in Koreans.
AB  - The proliferation of colorectal epithelial cells is regulated by various stimuli
      including cytokines and growth factors, thus the variants of those genes can
      modify the colorectal cancer risk. TGF-[beta]1 can act as both a tumor suppressor
      and a stimulator of tumor progression. TGF-[beta]1 C-509T polymorphism in the
      promoter sequence has been associated with increased levels of plasma TGF-[beta]1
      in individuals with T allele. To evaluate the potential influences of this
      polymorphism on colorectal adenoma and cancer risk, a case-control study was
      conducted in Korea. A total of 646 subjects were prospectively enrolled in Seoul
      National University Hospital. Risk of colorectal neoplasms was evaluated
      separately for 244 patients with colorectal adenoma, 152 patients with colorectal
      cancer relative to 250 healthy controls. Genotypes were determined by the PCR
      RFLP method. ORs and 95% CIs were calculated by a multivariate logistic
      regression analysis. The TGF-[beta]1 -509T allele containing genotypes posed a
      reduced risk of colorectal cancer (adjusted OR = 0.59, 95% CI = 0.28-0.92). But
      there was no association between this polymorphism and colorectal adenoma. Our
      results suggest that the TGF-[beta]1 -509T allele may have a protective role in
      the development of colorectal cancer, possibly consistent with its role as an
      inhibitor of epithelial malignant transformation.

PMID- 17214747
TI  - Evidence of a novel antiapoptotic factor: role of inhibitor of differentiation or
      DNA binding (Id-1) in anticancer drug-induced apoptosis.
AB  - Id-1 (inhibitor of differentiation or DNA binding), a member of the basic helix
      loop-helix transcription factor family, is up-regulated in many types of human
      cancer and its expression levels are correlated with poor treatment outcome and
      shorter survival. In this study, we provided evidence to suggest that Id-1 is a
      universal survival factor that plays a key role in protection against anticancer
      drug-induced apoptosis. Using nine anticancer drugs and five cancer cell lines
      derived from nasopharyngeal carcinoma (CNE1), cervical carcinoma (HeLa), breast
      cancer (MCF7), hepatocarcinoma (Huh7) and prostate cancer (PC3), we found that
      down-regulation of Id-1 expression at both transcriptional and protein levels was
      associated with increased apoptosis rates and increased cleaved PARP after
      exposure to all anticancer agents. Treatment with a caspase 9 inhibitor, Z-LEHD
      FMK, protected cancer cells from drug-induced PARP cleavage. However,
      overexpression of Id-1 in a p53 mutated cell line, CNE1, was able to suppress
      PARP cleavage in response to all anticancer drugs examined. In contrast, down
      regulation of Id-1 through small RNA technology in CNE1 cells led to increased
      sensitivity to all six types of chemotherapeutic drugs. Our results demonstrate
      that Id-1 may be a general negative regulator of anticancer drug-induced
      apoptosis and suggest a novel therapeutic target in inducing chemosensitization
      in cancer cells. Our evidence also provides a possible underlying mechanism
      responsible for the positive role of Id-1 in the progression of human cancer.

PMID- 17214748
TI  - Relational ethics and advocacy in nursing: literature review.
AB  - AIM: The purpose of this paper is to analyse themes from accounts of nurses'
      experiences with advocacy that may expand our understanding of advocacy in
      nursing practice. BACKGROUND: Although the ethical obligation to advocate is
      universal, a lack of clarity persists about the nature of advocacy in nursing
      practice. METHOD: This discussion of advocacy is based on a synthesis of
      qualitative studies that focus on nurses' experiences with advocacy in practice.
      Empirical studies were retrieved through searches on the CINAHL and Academic
      Search Premier databases for the years 1993-2005. The search terms used were
      advocacy, advocate role, ethics, nursing practice and qualitative research.
      FINDINGS: Empirical studies related to the role of advocacy in nursing are
      limited in number. Nurses' experiences with advocacy reveal important themes in
      relation to factors that influence the application of advocacy in nursing
      practice. Evidence suggests that the nature and context of relationships plays a
      significant role in influencing the enactment of advocacy. CONCLUSION: The
      application of advocacy in nursing practice is complex. The philosophy of
      relational ethics emphasizes the contextual features of relationships. An
      examination of relational ethics as it applies to advocacy in nursing brings us
      closer to a deeper understanding of the process by which nurses make advocacy
      choices in practice, and raises implications for the development of advocacy in
      nurses' practice. Advocacy is universally considered a moral obligation in
      nursing practice, and thus advancement of our knowledge about its nature in
      nursing is relevant to nursing across multiple contexts and cultures.

PMID- 17214749
TI  - Expert intrapartum maternity care: a meta-synthesis.
AB  - AIM: This paper reports a meta-synthesis exploring the accounts of intrapartum
      midwifery skills, practices, beliefs and philosophies given by practitioners
      working in the field of intrapartum maternity care who are termed expert,
      exemplary, excellent or experienced. BACKGROUND: Expertise in nursing and
      medicine has been widely debated and researched. However, there appear to be few
      studies of practitioners' accounts of expertise in the context of maternity care.
      Given current international debates on the need to promote safe motherhood, and,
      simultaneously, on the need to reverse rising rates of routine intrapartum
      intervention, an examination of the nature of maternity care expertise is timely.
      METHOD: A systematic review and meta-synthesis were undertaken. Twelve databases
      and 50 relevant health and social science journals were searched by hand or
      electronically for papers published in English between 1970 and June 2006, using
      predefined search terms, inclusion, exclusion and quality criteria. FINDINGS:
      Seven papers met the criteria for this review. Five of these included qualified
      and licensed midwives, and two included labour ward nurses. Five studies were
      undertaken in the USA and two in Sweden. The quality of the included studies was
      good. Ten themes were identified by consensus. After discussion, three
      intersecting concepts were identified. These were: wisdom, skilled practice and
      enacted vocation. CONCLUSION: The derived concepts provide a possible first step
      in developing a theory of expert intrapartum non-physician maternity care. They
      may also offer more general insights into aspects of clinical expertise across
      healthcare groups. Maternity systems that limit the capacity of expert
      practitioners to perform within the domains identified may not deliver optimal
      care. If further empirical studies verify that the identified domains maximize
      effective intrapartum maternity care, education and maternity care systems will
      need to be designed to accommodate them.

PMID- 17214750
TI  - Effects of aquatic exercise on flexibility, strength and aerobic fitness in
      adults with osteoarthritis of the hip or knee.
AB  - AIM: This paper reports a study of the effects of aquatic exercise on physical
      fitness (flexibility, strength and aerobic fitness), self-reported physical
      functioning and pain in adults with osteoarthritis of the hip or knee.
      BACKGROUND: Osteoarthritis is a common cause of disability and a primary reason
      for hip and knee joint replacement. Exercise is important for preventing and/or
      managing the functional limitations associated with joint disease. Aquatic
      exercise is thought to be beneficial and is often recommended for people with
      osteoarthritis; however, few studies have examined the effects on people with
      osteoarthritis, and these have yielded inconsistent results. METHODS: A two-group
      randomized controlled trial with a convenience sample was used. Participants were
      recruited from community sources and randomly assigned to a 12-week aquatic
      programme or a non-exercise control condition. Data for 38 participants were
      collected at baseline, week 6, and week 12 during 2003 and 2004. Instruments were
      a standard plastic goniometer, a handheld dynamometer, the 6-minute walk test,
      the multidimensional Health Assessment Questionnaire, and a visual analogue scale
      for pain. RESULTS: Repeated measures analysis of variance showed that aquatic
      exercise statistically significantly improved knee and hip flexibility, strength
      and aerobic fitness, but had no effect on self-reported physical functioning and
      pain. The exercise adherence rate was 81.7%, and no exercise-related adverse
      effect was observed or reported. CONCLUSIONS: Beneficial short-term effects of
      aquatic exercise were found in adults with osteoarthritis of the hip or knee.
      Although the programme may not offer pain relief or self-reported improvements in
      physical functioning, results suggest that aquatic exercise does not worsen the
      joint condition or result in injury. Nurses engaging in disease management and
      health promotion for these patients should consider recommending or implementing
      aquatic classes for patients.

PMID- 17214751
TI  - Junior staffing changes and the temporal ecology of adverse incidents in acute
      psychiatric wards.
AB  - AIM: This paper reports an examination of the relationship between adverse
      incident rates, the arrival of new junior staff on wards, and days of the week on
      acute psychiatric wards. BACKGROUND: Incidents of violence, absconding and self
      harm in acute inpatient services pose risks to patients and staff. Previous
      research suggests that the arrival of inexperienced new staff may trigger more
      adverse incidents. Findings on the relationship between incidents and the weekly
      routine are inconsistent. METHOD: A retrospective analysis was conducted of
      formally reported incident rates, records of nursing student allocations and
      junior doctor rotation patterns, using Poisson Regression. Variance between days
      of the week was explored using contingency table analysis. The data covered 30
      months on 17 psychiatric wards, and were collected in 2002-2004. FINDINGS: The
      arrival of new and inexperienced staff on the wards was not associated with
      increases in adverse incident rates. Most types of incidents were less frequent
      at weekends and midweek. Incident rates were unchanged on ward-round days, but
      increased rates were found on the days before and after ward rounds. CONCLUSION:
      Increased patient tension is associated with raised incident rates. It may be
      possible to reduce incident rates by moderating stimulation in the environment
      and by mobilizing support for patients during critical periods.

PMID- 17214752
TI  - Role development and career stages in addiction nursing: an exploratory study.
AB  - AIM: This paper reports a study to explore factors influencing recruitment and
      retention in addiction nursing, and the stages and features of role acquisition
      and personal qualities important to that role. BACKGROUND: Specialist addiction
      nurses engage in a number of roles in the care of individuals with problematic
      use of psychoactive substances. These include assessment, outreach, prescribing,
      counselling, and harm reduction. In a climate of increasing demand for specialist
      substance misuse workers, and a trend to identify key occupational competencies,
      there is a need for a framework in which career progression can be supported.
      Studies exploring the roles of addiction nurses are minimal, and there is less
      comment on how these roles are developed in the context of career stages. METHOD:
      A qualitative study using focus groups was undertaken with specialist addiction
      nurses between March and June 2004. The data were transcribed verbatim and
      analysed using Burnard's six content analysis stages. FINDINGS: Positive factors
      identified as influencing recruitment and retention included: prior knowledge of
      the working environment (as a nursing student), opportunities for autonomous
      practice, the client profile, and associated treatment philosophy and care
      approach. There was consensus that nurses choosing to work in the field of
      addiction needed, in addition to being non-judgmental, personal qualities
      including hardiness, patience and tolerance. Five role development stages, with a
      set of descriptors, were identified: encounter, engagement, stabilization,
      competency and mastery. CONCLUSION: Identification of these five role development
      stages for addiction nurses offers employers, nurse managers, educators and
      addiction nurses a starting point from which specific occupational competencies
      can be further explored. In addition, continuing professional development needs
      can be mapped to specific role development stages. Employers and nurse managers
      may wish to offer increased learning opportunities to student nurses to gain work
      experience within specialist addiction units.

PMID- 17214753
TI  - Patients' accounts of the differences in nurses' and general practitioners' roles
      in primary care.
AB  - AIM: This paper reports a study of patients' accounts of the differences in
      nurses' and general medical practitioners' roles in primary care. BACKGROUND:
      Nurses are now diagnosing and treating illnesses including conducting first
      contact care consultations. However, the findings of international studies
      reporting patients' views of developments in nursing roles are not consistent.
      Whilst some studies report higher satisfaction following nurse consultations,
      others suggest that patients do not want nurses to replace general medical
      practitioners. Healthcare professionals' views of the boundaries of their roles
      have been studied, but patients' views have not been reported. METHOD: Semi
      structured interviews were conducted with 28 adults attending general practices
      for urgent 'same day' appointments during 2004. Participants were interviewed
      prior to their consultation with either the nurse or general medical practitioner
      and 19 participants were interviewed after the consultation. Data collection and
      analysis were concurrent, and based on the constant comparative method. FINDINGS:
      Participants' views reflected traditional hierarchies in primary care. They
      preferred to consult with general medical practitioners if they perceived their
      symptoms to be serious and with nurses for minor symptoms and reassurance. They
      thought that nurses had more time for them and were more compassionate.
      Interpersonal/relational continuity of care was important and for most
      participants this was with a general medical practitioner who knew them.
      Participants trusted known practitioners; they also placed trust in professional
      groups and familiar structures such as the practice. CONCLUSION: New nursing
      services should incorporate patients' views on continuity of care provider when
      developing models of care delivery. Patient information leaflets in general
      practices should be used to explain the roles of general practitioners and nurse
      practitioners/practice nurses. As these roles develop further, more research is
      needed into all aspects of their implementation and patients' views should
      particularly be evaluated.

PMID- 17214754
TI  - Effects of a range-of-motion exercise programme.
AB  - AIM: This paper reports an evaluation of a range-of-motion exercise programme
      aimed at improving joint flexibility, activity function, perception of pain, and
      depressive symptoms in a sample of stroke survivors in long-term care facilities.
      BACKGROUND: The benefits of physical rehabilitation for stroke survivors have
      been well established. There is, however, little empirical data on the effects of
      a simple nurse-led range-of-motion exercise programme in improving function for
      these people. METHOD: A randomized controlled trial was conducted in 1999 with 59
      bedridden older stroke survivors in residential care. Participants were randomly
      assigned to usual care or one of two intervention groups. The 4-week, twice-per
      day, 6 days-per-week range-of-motion exercise protocols were similar in both
      intervention groups, and consisted of full range-of-motion exercises of the upper
      and lower extremities. To test the effect of different degrees of staff
      involvement, in intervention group I, a Registered Nurse was present to supervise
      participants performing the exercises, while intervention group II involved a
      Registered Nurse physically assisting participants to achieve maximum range-of
      motion within or beyond their present abilities. RESULTS: Both intervention
      groups had statistically significant improvement in joint angles, activity
      function, perception of pain and depressive symptoms compared with the usual care
      group (P < 0.05). Post hoc comparison revealed that the joint angles in
      intervention group II were statistically significantly wider than in both the
      other groups (P < 0.01). CONCLUSIONS: A simple nurse-led range-of-motion exercise
      programme can generate positive effects in enhancing physical and psychological
      function of bedridden older people with stroke. Further studies are needed to
      investigate the long-term effects of the programme in maximizing function,
      reducing care utilization and enhancing quality of life for this population.

PMID- 17214755
TI  - The effectiveness of implementing a bladder ultrasound programme in neurosurgical
      units.
AB  - AIM: This paper reports an evaluation of the differences among rates of
      unnecessary catheterization, urinary retention and urinary tract infection before
      and after implementing a bladder ultrasound programme to assess urine volume.
      BACKGROUND: Bladder ultrasound is a non-invasive alternative to urethral
      catheterization for the determination of bladder urine volume. Much of the
      literature available on bladder ultrasound technology addresses the accuracy of
      the equipment, with little research on the clinical outcomes or benefits of the
      intervention. METHODS: A quasi-experimental design was adopted. Data were
      collected from March 2001 to May 2001 in a control group in two neurosurgical
      units in Taiwan. During July and August 2001, nurses were taught how to operate a
      portable ultrasound machine and how to implement the programme. Data were
      collected from September to November 2001 in the study group. RESULTS: The rates
      of unnecessary catheterization in the control group and the study group were
      35.3% and 7.0%, respectively. The urine volume (more than 500 mL) in the control
      group and the study group were 13.4% and 20.3%, respectively. The study group had
      a statistically significantly lower average catheterization volume than that of
      the control group (676.9 mL vs. 777.1 mL, t = 1.84, P < 0.05). During 3 months
      before and after the implementation of the programme, the urinary tract infection
      rates in the control group and the study group were 3.47% and 2.87%,
      respectively. After 6 months the urinary tract infection rates decreased to
      1.39%. CONCLUSION: The bladder ultrasound programme was successful and could be
      used to manage patients with urination disorders in neurosurgical units.

PMID- 17214756
TI  - Psychometric properties of the Multifactor Leadership Questionnaire among nurses.
AB  - AIM: This paper reports a study investigating the psychometric properties of the
      Multifactor Leadership Questionnaire among nurses. BACKGROUND: Although the
      Multifactor Leadership Questionnaire is one of the most widely used instruments
      to measure the multifactor leadership theory in organizational sciences,
      inconsistent research findings have been reported for its psychometric
      properties. Little is known about these properties. METHOD: Data were gathered by
      postal questionnaires in 2001-2002 with nurses working in different healthcare
      organizations in Finland. A follow-up study was performed 1-year later. The
      sample consisted of 601 nurses and nurse leaders, and the follow-up study had 78
      respondents. The internal consistency of the Multifactor Leadership Questionnaire
      was explored using Cronbach's alpha coefficient and item-analysis, and the test
      retest reliability using Pearson product moment correlation coefficient and intra
      class correlation coefficient (single measure intra-class correlation
      coefficient). The factor structure was studied using exploratory and confirmatory
      factor analyses. RESULTS: The internal consistencies of the leadership subscales
      were satisfactory. The Multifactor Leadership Questionnaire was fairly stable
      measured at the 1-year interval. Although the data fail to support the full nine
      factor model, a reduced set of items from the Multifactor Leadership
      Questionnaire appears to show evidence of the three- and six-factor structures.
      Exploratory factor analysis showed evidence for the three-factor structure
      consisting of three distinctive, yet partly related leadership subscales.
      Confirmatory factor analysis showed evidence for the six-factor structure.
      CONCLUSION: The psychometric data suggest that a modified version of the
      Multifactor Leadership Questionnaire is a highly suitable instrument to measure
      multidimensional nursing leadership. Validity and reliability were supported. The
      results can be used in studies applying the Multifactor Leadership Questionnaire.

PMID- 17214757
TI  - Spiritual care in Christian parish nursing.
AB  - AIM: This paper reports the development of a substantive theory to explain the
      process parish nurses use to provide spiritual care to parishioners in Christian
      churches in a context where patients and nurses share a common set of values.
      BACKGROUND: Despite a surge of interest in spirituality and spiritual care in
      nursing, consensus is lacking on how care should be conceptualized and provided.
      METHOD: Grounded theory method was used to explore and describe the processes 10
      American parish nurses experienced and used as they gave spiritual care. Data
      were collected between 1998 and 2001. Participants were interviewed and
      audiotapes transcribed verbatim. Constant comparative methods were used to
      analyse more than 50 separate incidents reported by the nurses. FINDINGS: From
      its initial emergence as the core category, 'Bringing God Near' became a Basic
      Social Process theory of giving spiritual care for these parish nurses. This
      Basic Social Process became a theory through writing theoretical memos that
      described how the 'main concern' of the nurses to give spiritual care was
      resolved. Phases within the process include: trusting God, forming relationships
      with the patient/family, opening to God, activating/nurturing faith and
      recognizing spiritual renewal or growth. The essence is bringing God near to
      people as they face health challenges. Findings from the study and spiritual care
      literature are integrated in the discussion. CONCLUSION: The parish nurses'
      spiritual challenge is to respond to what God is directing the nurse to be and do
      to strengthen people spiritually. This spiritual care can help restore the
      patient's sense of well-being, and encourage growth in faith. Those interested in
      providing and teaching spiritual care in the church context will find this theory
      useful as a conceptual guide.

PMID- 17214764
TI  - Age-dependent expression and localization of the progesterone receptor in the
      boar testis.
AB  - Expression of the progesterone receptor (PR) was monitored in testes of groups of
      five boars aged 50, 100, 150, 200 and 250 days. The primary monoclonal antibody
      used for immunohistochemistry (IHC) was raised against a peptide mapping the
      amino acids 922-933 of the carboxy-terminus of the human PR, negative controls
      were set up using an irrelevant monoclonal isotype-specific antibody, porcine
      endometrium served as positive control tissue. In parallel, qualitative reverse
      transcription-polymerase chain reaction was applied. Based on the developmental
      status of spermatogenesis the 50- and 100-day-old boars were considered as
      immature, the boars aged 200 and 250 days as mature. Positive and negative
      controls confirmed specificity of IHC. In the 50-day-old boars 85.1% of the
      prespermatogonia that had reached the basal lamina and 18.2% of the centrally
      located prespermatogonia stained positive, while it was 92.1% respectively 2.1%
      in the 100-day-old boars. The effect of time and location was highly significant
      (p < 0.005 resp. 0.0001). In mature boars between 77 and 80% of the A and B
      spermatogonia stained positive, there was no effect of boar age and stage of
      spermatogenesis. In both groups also few peritubular myoid cells stained
      positive. It is hypothesized that Leydig cell-derived progesterone plays a
      functional role in spermatogoniogenesis in a synergistic manner with Leydig cell
      derived oestrogens.

PMID- 17214765
TI  - Postpartum ovarian activity and serum estradiol-17beta level in Thai crossbred
      native mares.
AB  - To study the postpartum ovarian activities for investigation of first postpartum
      oestrus, twenty-five Thai crossbred native mares were monitored after parturition
      by oestrous detection, transrectal palpation and reproductive ultrasonography.
      Blood samplings were also taken for estradiol-17beta (E2) analysis. The first
      ovulation occurred within 20 days postpartum in 92% (23/25) of the mares. The
      mean intervals of foaling to first oestrus and to first ovulation were 10.3 +/-
      2.9 and 13.4 +/- 2.6 days (mean +/- SD) respectively. Serum E2 increased from 7.0
      +/- 2.9 to a peak of 10.8 +/- 3.3 pg/ml (mean +/- SD) at 2 days before ovulation.
      In conclusion, from the study, it can be stated that the postpartum breeding
      management should be considered after day 10 postpartum by careful examination of
      ovarian activity with various methods. However, the uterine condition should be
      also estimated associated with the ovarian activity after parturition which may
      increase breeding performance and foal production.

PMID- 17214766
TI  - Evaluation of fertilizing potential of frozen-thawed dog spermatozoa diluted in
      ACP-106 using an in vitro sperm--oocyte interaction assay.
AB  - The aim of present study was to evaluate frozen canine semen with ACP-106 (Powder
      Coconut Water) using an in vitro sperm--oocyte interaction assay (SOIA). Ten
      ejaculates from five stud dogs were diluted in ACP-106 containing 20% egg yolk,
      submitted to cooling in a thermal box for 40 min and in a refrigerator for 30
      min. After this period, a second dilution was performed using ACP-106 containing
      20% egg yolk and 12% glycerol. Samples were thawed at 38 degrees C for 1 min.
      Post-thaw motility was evaluated by light microscopy and by using a computer
      aided semen analysis (CASA). Plasma membrane integrity and sperm
      morphology/acrosomal status were evaluated by fluorescent probes (C-FDA/PI) and
      Bengal Rose respectively. Moreover, frozen-thawed semen was analysed by a SOIA.
      Subjective post-thaw motility was 52.0 +/- 14.8% and it was significant higher
      than the total motility estimated by CASA (23.0 +/- 14.8%) because this system
      considered the egg yolk debris as immotile spermatozoa. Although normal sperm
      rate and acrosomal integrity evaluated by Bengal Rose stain was 89.6 +/- 3.1% and
      94.3 +/- 3.1%, respectively, post-thaw percentage of intact plasma membrane was
      only 35.1 +/- 14.3%. Regarding SOIA, the percentage of interacted oocytes (bound,
      penetrated and bound and/or penetrated) was 75.3%. Using regression analysis, it
      was found significant relations between some CASA patterns and data for SOIA. In
      conclusion, the freezing-thawing procedure using ACP-106 was efficient for
      maintain the in vitro fertility potential of dog spermatozoa.

PMID- 17214767
TI  - Assessment of sperm apoptosis in cryopreserved bull semen after swim-up
      treatment: a flow cytometric study.
AB  - The techniques used to prepare bovine spermatozoa for in vitro fertilization, to
      enhance the percentage of motile sperm cells include the swim-up (SU) method,
      among others. The objective of the present study was to evaluate the
      phosphatidylserine (PS) translocation and plasma membrane integrity as the
      indicator of apoptosis and necrosis in post-thaw bull sperm after SU treatment
      using annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) assay. A
      flow cytometric method was employed to measure apoptosis levels on frozen-thawed
      bull spermatozoa. The assay detects PS translocation across the plasma membrane
      using a fluorescein-labelled annexin-V and PI. By using the annexin V/PI assay
      four different subpopulations of sperm were observed: (i) a population of
      apoptotic sperm, labelled with annexin V-FITC but not with PI; (ii) a population
      of early necrotic spermatozoa, sperm labelled with annexin-FITC and PI; (iii) a
      population of necrotic sperm, labelled with PI but not with annexin-FITC; and
      (iv) a population of fully viable sperm cells, sperm not labelled with annexin V
      FITC and without PI. Results clearly indicated that SU technique itself could
      have an adverse effect on the spermatozoa membrane stability. It has also been
      found, significant differences between bulls in the levels of apoptotic sperm,
      after SU treatment.

PMID- 17214768
TI  - Immunohistochemical localization of androgen receptor in two subpopulations of
      porcine granulosa cells in vitro.
AB  - In the ovarian follicles of mammals, androgens are utilized as substrates for
      estrogen synthesis or can act via androgen receptor (AR). Within the ovary,
      granulosa cells generally display the strongest immunoreactivity for AR protein.
      Therefore, the aim of the present study was to analyse possible changes in the
      intensity of AR staining in cultured mural and antral granulosa cells isolated
      from follicles at various stages of development. Porcine ovaries were obtained at
      a local slaughterhouse and the follicles were classified as small, medium and
      large dependently on their diameter. Isolated granulosa cells were separated into
      two populations, mural and antral, and then the cells were cultured during 48 h.
      After this time the cells were fixed and immunostained to visualize the AR.
      Androgen receptor immunostaining was detected in both, antral and mural granulosa
      cell cultures isolated from follicles at all stages of the development. In the
      mural granulosa cultures the immunostaining was comparatively weaker than that in
      the antral granulosa cells originating from all types of follicles. Our results
      provide immunohistochemical evidence that antral granulosa layer is the main site
      of AR immunoexpression.

PMID- 17214769
TI  - Effect of cloprostenol treatment at artificial insemination on sow fertility.
AB  - In two experiments, we examined the effect of administration of cloprostenol at
      artificial insemination on fertility of multiparous sows. Lactation length was 21
      days and only sows exhibiting estrus by 7 days after weaning were included.
      Cloprostenol was administered by IM injection (175 microg; n=126) or supplemented
      in the semen dose (525 microg; n=129). Control sows (n=130) received no hormone.
      In either experiment, there was no effect of any treatment on subsequent litter
      sizes. In experiment 1, there was no effect of treatment on farrowing rate, but
      in experiment 2, farrowing rate was higher (p < 0.05) in sows receiving
      cloprostenol by injection. Taken together, these results indicate no consistent
      effect of cloprostenol administration by intramuscular injection or by inclusion
      in the semen dose on sow fertility and so its routine use is not warranted.

PMID- 17214770
TI  - Effects of breed on follicular dynamics and oestradiol secretion during the
      follicular phase in sheep.
AB  - Current study evaluates effects from breed and management background on
      follicular dynamics and endocrine output during the follicular phase of sheep
      oestrous cycle. Follicular phases were synchronized with three cloprostenol
      doses, 10 days apart, in three groups of 10 females of different non-prolific
      Spanish breeds (Manchega, Rubia del Molar and Negra de Colmenar). Development of
      all follicles reaching antral diameters >or=2 mm was assessed by daily
      transrectal ultrasonographies, whereas follicular function was evaluated by
      measurement of plasma oestradiol concentrations. All the ovulatory follicles were
      present at induced luteolysis in Manchega sheep, while a 93.7% were detected in
      Rubia del Molar and Negra de Colmenar ewes. The mean size of these ovulatory
      follicles was similar between breeds at 0 h, but their growth rates were higher
      in Manchega ewes, reaching a larger size at oestrous detection than in Negra de
      Colmenar and Rubia del Molar sheep (p < 0.05). Conversely, the oestradiol levels
      increased with time in Rubia del Molar and Negra de Colmenar (p < 0.05); whilst
      remained stable in Manchega females. However, the patterns of follicular turnover
      were similar between breeds. These results indicate that, though differences in
      follicular size and size distribution, patterns of follicular turnover in sheep
      are affected neither by the breed nor by the background of management and
      selection.

PMID- 17214771
TI  - Vitrification of boer goat morulae and early blastocysts by straw and open-pulled
      straw method.
AB  - The aim of this study was to investigate the effects of different vitrification
      solutions [EFS30 or EFS40 contains 30% (v/v) ethylene glycol (EG), 40% (v/v) EG;
      EDFS30 or EDFS40 contains 15% (v/v) EG and 15% (v/v) dimethyl sulfoxide (DMSO),
      20% (v/v) EG and 20% (v/v) DMSO], equilibrium time during vitrification (0.5-2.5
      min) and vitrification protocols [one-step straw, two-step straw and open-pulled
      straw (OPS)] on in vivo development of vitrified Boer goat morulae and
      blastocysts after embryo transfer. In the one-step straw method, the lambing
      rates of vitrified embryos in EFS30 (37.5%), EFS40 (40.5%) or EDFS30 (38.2%)
      group were similar to that of fresh embryos (57.5%) and conventional freezing
      method (46.7%) when the equilibrium time was 2 min. In the two-step straw method,
      the highest lambing rate was obtained when embryos were pretreated with 10% EG
      for 5 min and then exposed to EFS40 for 2 min (51.4%), showing similar lambing
      rates compared with fresh embryos (56.1%) or the embryos cryopreserved by
      conventional freezing method (45.2%). In the OPS method, the lambing rate in
      EFS40, EDFS30 or EDFS40 groups were similar to that (57.1%) of fresh embryos, or
      to that (46.0%) of embryos cryopreserved by conventional freezing method. The
      highest lambing rate (51.4%) of the group of OPS was obtained when the embryos
      were vitrified with EDFS30. In conclusion, either the two-step straw method in
      which embryos were pretreated in 10% EG for 5 min and then exposed to EFS40 for 2
      min, or the OPS method in which embryos were pretreated in 10% EG + 10% DMSO for
      30 s and then exposed to EDFS30 for 25 s was a simple and efficient method for
      the vitrification of Boer goat morulae and blastocysts.

PMID- 17214772
TI  - Acyl ghrelin and metabolic hormones in pregnant and lactating sows.
AB  - Ghrelin, the endogenous ligand of the growth hormone (GH) secretagogue receptor,
      is considered a pleiotropic regulator involved in a large array of functions,
      including control of energy balance, regulation of food intake and, more
      recently, modulation of the reproductive axis. The present study was aimed at
      determining the changes in plasma concentrations of acyl-ghrelin in pregnant and
      lactating sows, with special emphasis on the relationship with the levels of GH,
      leptin, non-esterified fatty acids (NEFA) and insulin-like growth factor (IGF-1).
      Blood samples were collected via jugular venipuncture from 22 multiparous sow 30,
      60 and 90 days after artificial insemination, 7 and 21 days after farrowing and
      at first oestrus post-weaning. Plasma concentrations of acyl-ghrelin, leptin, GH
      and IGF-1 were quantified by validated radioimmunoassay; NEFA were determined
      using a colorimetric procedure. Plasma acyl ghrelin levels were highest at 30
      days of pregnancy and decreased thereafter and during lactation. At the beginning
      of lactation, GH, IGF-1 and NEFA concentrations significantly increased, while a
      significant reduction occurred in leptin. In conclusion, ghrelin concentrations
      in sow maternal circulation does not seem to play an important role in
      maintaining circulating GH levels during lactation; moreover, ghrelin is not
      associated with leptin, NEFA and IGF-1 levels.

PMID- 17214773
TI  - Cellular composition and viability of cloned bovine embryos using exogene
      transfected somatic cells.
AB  - The present study compared the efficiency of transgenic (TG) cloned embryo
      production by somatic cell nuclear transfer (SCNT) with fetal-derived fibroblast
      cells (FFCs) which were transfected with pEGFP-N1 to in vitro-fertilized (IVF),
      parthenogenetic and SCNT counterparts by evaluating the rates of cleavage and
      blastocyst formation, apoptosis rate at different developmental stages, cell
      number, ploidy and gene expression in blastocysts. In SCNT and TG embryos, the
      rates of cleavage and blastocyst formation were significantly lower (p < 0.05)
      than those of IVF controls, but it did not differ between SCNT and TG embryos. In
      IVF control, 86.7% embryos displayed diploid chromosomal complements and the
      rates were significantly (p < 0.05) higher than those of SCNT and TG embryos.
      Most TG embryos (79%) with FFCs expressed the gene by both PCR and under
      fluorescence microscopy. The expression of apoptosis by TUNEL was first detected
      at six to eight cell stages in all embryos of IVF, SCNT and TG groups, but the
      expression rate at each developmental stages was significantly higher (p < 0.05)
      in SCNT and TG embryos than in IVF counterparts. The expression rate in inner
      cell mass (ICM) of TG embryos was significantly higher (p < 0.05) than in SCNT
      and IVF embryos. These results indicate that the high occurrence of apoptosis
      observed in SCNT and TG embryos compared with IVF counterparts might influence
      the developmental competence. Moreover, the SCNT embryos derived using non
      transfected donor cells exhibited a lower apoptosis expression in ICM cells than
      in TG embryos derived using pEGP-N1-transfected donor cells suggesting a possible
      role of negative gene effect in TG embryos.

PMID- 17214774
TI  - Cryopreservation of sheep primordial follicles.
AB  - The aim of this study was to evaluate the efficiency of 1 M dimethylsulphoxide
      (DMSO), ethylene glycol (EG), propylene glycol (PROH) and glycerol (GLY) to
      cryopreserve primordial follicles. The first evaluation was performed soon after
      cryopreservation and the second evaluation after 4 days of in vitro culture,
      using the cryoprotectants that allowed the higher results (higher follicular
      survival rate) after cryopreservation. The results after follicular isolation
      (control) and cryopreservation using 1 M DMSO, EG, PROH and GLY showed that the
      mean number (+/- SEM) of live follicles per millilitre was 3204 (100%) +/-
      319.27, 2798 (87%) +/- 239.14, 2492 (78%) +/- 345.8, 448 (14%) +/- 46.3 and 208
      (7%) +/- 75.26, respectively. Higher follicular survival was reported when DMSO
      and EG were used. Control follicles and follicles cryopreserved with these two
      cryoprotectants were cultured and the percentage of follicular survival was 55%
      (control), 42% (EG) and 34% (DMSO). Similar results were found between control
      and follicles cryopreserved with EG. In conclusion, 1 M EG is the most effective
      cryoprotectant to preserve primordial follicles isolated from ovaries of sheep.

PMID- 17214775
TI  - Insemination with sex sorted fresh bovine spermatozoa processed in the presence
      of antioxidative substances.
AB  - Flow cytometrically sex sorted spermatozoa are reduced in their fertilizing
      capacity, particularly when stored either in cooling extender or after freezing
      in liquid nitrogen. So far, preservation methods for sorted spermatozoa have
      differed only marginally from procedures used for unsorted semen. In the present
      study, a TRIS extender was modified to balance major cell damage caused by the
      sorting process and by liquid storage of the sorted spermatozoa. The new
      extender, containing a combination of antioxidants (AO) and bovine serum albumin
      (BSA), significantly increased the lifespan and fertilizing capacity of sex
      sorted spermatozoa. No significant differences were observed between unsorted
      controls and sorted samples for motility and status of sperm membranes as tested
      by fluorescein-isothiocyanat-peanut agglutinin/propidium iodide (FITC-PNA/PI).
      Acrosome integrity of spermatozoa was significantly better when semen was stored
      at 15 degrees C for 24 and 48 h in an extender containing AO with or without BSA
      as compared with controls (p < 0.05). There were no significant differences, in
      pregnancy rates of heifers inseminated at a natural oestrus, between unsorted
      controls (16/24, 66.7%) and both sorted groups (AO + BSA: 18/31, 58.1% and AO
      BSA: 12/22, 54.5%). Additionally, it was shown for the first time that artificial
      insemination (AI) with liquid sexed bull spermatozoa stored for 72 h after
      sorting can result in pregnancy rates similar to AI with non-sorted semen.

PMID- 17214776
TI  - Reduction of oxidative stress in bovine spermatozoa during flow cytometric
      sorting.
AB  - The goal of the study was to investigate the effect of antioxidant
      supplementation on the quality of frozen-thawed flow cytometrically sorted bull
      spermatozoa. Twelve ejaculates from two Holstein Friesian bulls were sorted
      according to the Beltsville Sperm Sexing Technology. Each ejaculate was divided
      into three parts and processed as (i) unsorted controls, (ii) according to a
      standard sorting protocol and (iii) in the presence of different antioxidants (S
      AO). Cooling and freezing of the samples were performed in the same way for all
      three groups, except that antioxidants were added to the TRIS-egg-yolk freezing
      extender for those semen samples that were already sorted in the presence of
      antioxidants. The semen quality in frozen-thawed samples was determined by
      morphology analysis immediately after thawing, motility estimation in a thermo
      resistance test after 0, 6, 12 and 24 h incubation at 37 degrees C and
      Fluorescein isothiocyanate conjugated PNA/propidium iodide (FITC-PNA/PI) staining
      after 0, 12 and 24 h of incubation at 37 degrees C. There was a significantly
      higher (p < 0.05) percentage of motile spermatozoa in S-AO samples in comparison
      to unsorted frozen-thawed control at 0, 6 and 24 h after thawing and compared
      with normally sorted samples at all times after thawing. The percentage of
      damaged acrosomes was significantly lower (p < 0.05) in S-AO samples than in the
      unsorted controls (20.8 +/- 6.9% vs 30.3 +/- 12.0%). The percentage of
      morphologically abnormal spermatozoa in this group was significantly lower (p <
      0.05) than in the unsorted controls and normally sorted samples (25.8 +/- 5.2%,
      36.0 +/- 12.5% and 35.1 +/- 7.4%, respectively). Analysis of frozen-thawed
      spermatozoa with FITC/PI revealed no significant difference in membrane integrity
      at 0 and 12 h after sorting, but after 24 h of incubation the S-AO samples had a
      significantly higher (p < 0.001) percentage of spermatozoa with intact membranes
      in comparison to unsorted controls and normally sorted semen (40.7 +/- 6.3%, 7.8
      +/- 4.7% and 7.4 +/- 4.6%, respectively). The percentage of acrosome-reacted
      spermatozoa was significantly lower (p < 0.05) in the S-AO samples than in the
      unsorted controls (14.1 +/- 7.5%, 23.4 +/- 5.4% and 28.8 +/- 6.3% vs 25.9 +/-
      14.4%, 38.5 +/- 16.7% and 79.8 +/- 4.1%, for 0, 12 and 24 h after thawing,
      respectively) and in comparison to normally sorted semen 24 h after thawing (67.3
      +/- 10.0%). This study demonstrates the highly protective effects of antioxidants
      on the quality of flow cytometrically sorted frozen-thawed bull spermatozoa.

PMID- 17214777
TI  - Comparative IFN-tau secretion after hatching by bovine blastocysts derived ex
      vivo and completely produced in vitro.
AB  - The interferon-tau (IFN-tau) secretion levels after hatching by bovine
      blastocysts derived from in vitro maturated oocytes (Group A) and from in vivo
      (Group B) were investigated considering embryo quality. Only very homogeneous
      blastocysts of excellent or good quality were considered from day 7 of culture
      (Group A) and day 7 after artificial insemination with frozen-thawed from the
      same bull used for in vitro fertilization (Group B). All embryos were
      individually cultured into a 50 microl droplet of synthetic oviduct fluid medium
      with 10% fetal calf serum. After 24-h culture both Group A (n=44) and B (n=40)
      secreted <54 pm IFN-tau. After 48-, 72-, 96- and 120-h culture, Group A daily
      secreted 143 +/- 24 pm IFN-tau (n=19) vs 85 +/- 12 pm IFN-tau (n=21) for Group B
      (p < 0.01), 491 +/- 128 pm IFN-tau (n=29) vs 216 +/- 37 pm IFN-tau (n=23) (NS),
      499 +/- 135 pm IFN-tau (n=26) vs 353 +/- 93 pm IFN-tau (n=21) (NS), 559 +/- 136
      pm IFN-tau (n=22) vs 333 +/- 75 pm IFN-tau (n=20) (NS), respectively. Taken all
      together during 5 days, Group A produced per embryo 1690 +/- 290 pm IFN-tau
      (n=22) vs 982 +/- 182 pm IFN-tau (n=20) for Group B (p < 0.05). For all culture
      time there were sizable percentages of embryos that did not produce
      concentrations of IFN-tau above a certain cut-off level, and as such were not
      used to compute the means. In respect of the embryo quality whatever the groups
      after days 7-12 of culture, IFN-tau secretions were 1815 +/- 453 pm (n=10) for
      the embryos of excellent quality vs 1356 +/- 200 pm (n=28) for those of good
      quality (NS) and 360 +/- 188 pm (n=4) (p < 0.05) for embryos of fair quality. A
      positive relationship between IFN-tau production and in vitro development of
      quality I embryos was observed, whatever the embryos origins and, the embryos
      completely produced in vitro secreted more IFN-tau than the embryos produced in
      vivo.

PMID- 17214778
TI  - Effects of storing pig ovaries at 4 or 20 degrees C for different periods of time
      on the morphology and viability of pre-antral follicles.
AB  - The purpose of this study was to evaluate the effect of cooling ovarian tissue on
      pig pre-antral follicles. Ovaries were maintained in saline solution (0.9%) at 4
      or 20 degrees C for 6, 12 or 18 h. After storage, pre-antral follicles were
      morphologically evaluated. While primordial follicles were not affected by the
      storage, the percentage of morphologically normal growing follicles was
      significantly reduced in ovarian tissue stored at 20 degrees C for 12 or 18 h. To
      test the viability of stored follicles, growing follicles isolated from ovaries
      stored at 4 degrees C for 18 h and at 20 degrees C for 6 h were cultured for 3
      days. Follicles stored in either condition presented the same growth pattern in
      vitro as fresh follicles. We conclude that storage of pig ovaries at 4 degrees C
      for up to 18 h or at 20 degrees C for up to 6 h does not affect the morphology of
      growing follicles or their ability to grow in vitro.

PMID- 17214779
TI  - In vitro fertilization and development of OPU derived goat and sheep oocytes.
AB  - The recent upgrade in IVP technology seen in cattle can be adapted to embryo
      production in small ruminants to overcome limitations exhibited by surgical
      procedures on preserving the reproductive potential of donors and the efficiency
      of embryo production. The aim of the present study was to assess the current
      procedures used in cattle for the production of IVP embryos in goats and sheep
      based on laparoscopic-aided ovum pick-up (LOPU) supplied oocytes. Sexually
      matured goat and sheep donors were treated during the breeding season with FSH
      and subjected to laparoscopic-guided follicular puncture under general
      anaesthesia. The collected cumulus-oocyte complexes were matured in medium 199
      and fertilized by frozen-thawed spermatozoa using Talp medium supplemented with
      heparin and oestrus-sheep serum. Cleaved ova were either cultured in sheep in
      vitro fertilization medium plus amino acids or transferred to sheep oviducts.
      Blastocyst rate, hatching rate and development rate up to term were used as
      markers of embryo function. The results obtained for goat and sheep involving 30
      and 35 donors respectively (10 and 9 LOPU sessions) were 81.2% and 85.2% of
      oocyte collection rate; 88.3% and 98.6% oocyte incubation rate; 85.6% and 76.0%
      fertilization rate; 82.4% and 93.4% of cleavage rate; 50.0% and 61.5% IVP
      blastocyst rate; 42.1% and 45.5% blastocyst rate in oviducts; 73.0% and 66.7%
      embryo survival up to term, respectively. The results are comparable to those
      obtained in small ruminants and in bovines suggesting that requirements for
      embryo production and development are similar.

PMID- 17214780
TI  - Morphology of dromedary camel oocytes and their ability to spontaneous and
      chemical parthenogenetic activation.
AB  - The present work was conducted to examine (1) the morphology of dromedary cumulus
      oocytes complexes (COCs), (2) to study the incidence of spontaneous development
      of oocytes in vivo and (3) to assess the ability of in vitro matured dromedary
      oocytes to chemical parthenogenetic activation compared with in vitro fertilized
      (IVF) oocytes. COCs were recovered from dromedary ovaries classified according to
      their morphology into six categories. Oocyte diameter was measured using eye
      piece micrometer. For chemical activation, COCs with at least three layers of
      cumulus-cells were in vitro matured (IVM) in TCM 199 + 10 microg/ml FSH + 10 IU
      hCG/ml + 10% FCS + 50 microg/ml gentamycin. COCs were incubated for 40 h at 38.5
      degrees C under 5% CO2 in humidified air. After IVM, matured oocytes with first
      polar body (first Pb) were divided into two groups. Group 1: activated in 7%
      ethanol (E) for 5 min followed by culture in 2 mM 6-dimethylaminopurin (6-DMAP, E
      D, subgroup 1) or 10 microg/ml cycloheximide (CHX, E CHX, subgroup 2) for 3.5 h
      at 38.5 degrees C under 5% CO2. In group 2, oocytes were activated using 50
      microM Ca A23187 (Ca A) for 5 min followed by culture in 2 mM 6-DMAP (Ca D,
      subgroup 3) or 10 microg/ml CHX(Ca CHX, subgroup 4) for 3.5 h at 38.5 degrees C
      under 5% CO2. For control group, IVM oocytes were fertilized using frozen-thawed
      camel spermatozoa separated by swim-up method then suspended in Fert-TALP medium
      supplemented with 6 mg/ml BSA (FAF) + 10 microg/ml heparin. In all groups,
      oocytes were in vitro cultured in SOFaa medium + 5% FCS and 5 microg/ml insulin +
      50 microg/ml gentamycin. Cleavage rate and embryo development were checked on
      Days 2, 5 and 8. An average of 11.3 +/- 0.3 COCs were recovered/dromedary ovary.
      Categories 1 and 2 represented 33.1% and 34.8%, respectively, and were
      significantly higher (p < 0.01) than the other categories (19.1, 9.2 and 2.6% for
      categories 3-5, respectively). Category 6 (embryo-like structures) represented
      1.2% of the recovered oocytes, staining of these embryo-like structures with
      orcien dye indicated the presence of divided cells with condensed nuclei.
      Dromedary oocytes averaged 166.2 +/- 2.6 microm in diameter with black cytoplasm.
      Chemical activation of IVM dromedary oocyte with first Pb in 7% ethanol or 50
      microM Ca A followed by culture in 2 mM 6-DMAP showed significantly higher (p <
      0.01) cleavage and developmental rates to the morula stage than oocytes activated
      using 7% ethanol or 50 microM Ca A followed by 10 microg/ml CHX or in vitro
      fertilized control group. Higher (p < 0.01) proportion of oocytes sequentially
      cultured in 10 microg/ml CHX or that in vitro fertilized were arrested at the 2-4
      cell stage compared with that cultured in 6-DMAP.

PMID- 17214781
TI  - Fertility results of artificial inseminations performed with liquid boar semen
      stored in X-cell vs BTS extender.
AB  - The objective of the present field study was to compare the fertility results for
      boar semen diluted in X-cell stored up to 4-5 days before artificial insemination
      (AI) with semen diluted in Beltsville thawing solution (BTS) used for AI
      following 2-3 days of storage (where the first day being the collection day). A
      total number of 2601 double inseminations in Norwegian herds were included in
      this two-trial study. All the boars used in the study were mature cross-bred
      Norwegian Landrace x Duroc (LD), which were routinely used for AI in Norway. The
      inseminated gilts and sows were Norwegian Landrace x Yorkshire (LY). The AI doses
      contained 2.5 billion spermatozoa, and consisted of a mixture of semen from
      three, occasionally four, boars (i.e. heterospermic semen). Fertility was
      measured in terms of the likelihood of farrowing and subsequent litter size. The
      fertility of the semen in both of the extenders was satisfactory and no
      significant differences were found either in semen stored 4-5 days in X-cell
      compared with 2-3 days in BTS or in semen stored 2-3 days in X-cell compared with
      2-3 days in BTS. The storage capability findings for the long-term extender X
      cell could significantly simplify the practical issues of semen production and
      the distribution of AI doses containing 2.5 billion spermatozoa. However, in pig
      production systems where all semen is used within 2-3 days, the short-term
      extender BTS is as good as the more expensive extender X-cell.

PMID- 17214782
TI  - Impact of exogenous ACTH during pro-oestrus on endocrine profile and oestrous
      cycle characteristics in sows.
AB  - Sows housed in freely moving groups have elevated cortisol levels until the rank
      order is established, which takes place within approximately 48 h. The aim of
      this investigation was to study the effect of repeated administration of
      synthetic adrenocorticotropic hormone (ACTH; Synacthen Depot), during the
      follicular phase (pro-oestrus) on oestrus, ovulation and endocrine parameters.
      Four multiparous sows were used. Follicular growth and ovulation were recorded by
      ultrasonography. The first oestrous cycle after weaning was used as control
      cycle. Onset of oestrus in the sow occurs 3-4 days after the time when plasma
      progesterone reaches a concentration of 8 nmol/l. The progesterone profile in the
      control cycle of the individual sow was used for estimation when the ACTH
      injections should start. In the third pro-oestrus ACTH (2.5 microg/kg) was given
      via an indwelling catheter every 2 h for 48 h. The sows were euthanased 4-6 days
      after onset of the third oestrus and the ovaries were examined. Cortisol levels
      were elevated during the treatment period (p < 0.05). The second cycle, in which
      the sows were injected with ACTH, was prolonged with 2.5 days compared with the
      control cycle (p < 0.05). The oestradiol pattern during oestrus was similar in
      the control and the treatment cycle in ovulating sows. Three sows had ovulated
      (fresh corpora lutea), but the ovaries contained additionally one or several
      luteinized follicles/cysts. In conclusion, ACTH administration during pro-oestrus
      caused a prolongation of the oestrous cycle and a disturbed follicular
      development.

PMID- 17214783
TI  - Effect of hCG stimulation on plasma androstenone concentrations and cytochrome b5
      levels in testicular tissue.
AB  - The effect of Human chorionic gonadotropin (hCG) stimulation on the
      concentrations of free and conjugated androstenone in plasma was studied in 34
      crossbred entire male pigs (Landrace x Swedish Yorkshire). Seventeen pigs were
      treated with hCG 4 days prior to slaughter and the remaining pigs were treated
      with sterile saline and served as controls. Blood samples were taken prior to hCG
      or saline injection and on the day before slaughter and analysed for
      concentrations of free and conjugated androstenone. Testicular tissue samples
      were taken at slaughter and analysed for the levels of cytochrome b5 (cyb5)
      protein. Here we have demonstrated for the first time that hCG stimulation causes
      an increase in the plasma levels of both free and conjugated androstenone. Not
      all animals responded in the same way to hCG treatment regarding levels of free
      and conjugated androstenone demonstrating that individual animals can have
      differences in their capacity to produce free and conjugated androstenone. We
      suggest that hCG treatment is a good way to determine the potential for
      androstenone conjugation when androstenone synthesis in the testis is high. The
      levels of cyb5 protein in the testis were slightly related (r=0.41, p < 0.10) to
      free androstenone levels in the pigs after hCG administration, although levels of
      cyb5 protein were not affected by hCG treatment.

PMID- 17214784
TI  - Bilateral testicular Leydig cells tumour in a donkey.
AB  - A rare case of a bilateral Leydig cells tumour located in the testis of a 15-year
      old donkey slaughtered normally is presented. Histologically, the testicular
      tumour showed neoplastic Leydig cells arranged in solid growth as a
      pseudoadenomatous packet type. To our knowledge, this is the first bilateral
      Leydig cells tumour, a neoplasm never reported in the donkey.

PMID- 17214785
TI  - Pregnancy diagnosis in cats using a rapid, bench-top kit to detect relaxin in
      urine.
AB  - Relaxin is a pregnancy-specific hormone in the queen and is produced by the
      placenta. Both serum and urinary relaxin levels can be used to diagnose and
      monitor pregnancy in the cat; however, only serum levels are commonly measured in
      practice. The present study aimed to assess whether urine could be used for the
      rapid diagnosis of pregnancy at an early stage in domestic cats using a bench-top
      kit to detect relaxin. Paired serum and urine samples were collected during the
      first month of gestation in six cats. The samples were tested by applying neat
      serum, urine or urine diluted in non-pregnant cat serum to the Witness Relaxin
      kit. Relaxin concentrations in the paired samples were also measured by
      radioimmunoassay. All undiluted urine samples from pregnant cats tested negative
      using the bench-top kit; however, the kit was able to detect relaxin in urine
      after dilution with non-pregnant cat serum. Using this as the test sample, the
      kit was accurate at diagnosing pregnancy from 28 days after mating and some
      samples tested positive at 21 days after mating. This preliminary work could lead
      to the development of a home pregnancy test for cats.

PMID- 17214786
TI  - MBI: M(I)BI agonistes or a new chapter?

PMID- 17214787
TI  - Molecular breast imaging: advantages and limitations of a scintimammographic
      technique in patients with small breast tumors.
AB  - Preliminary studies from our laboratory showed that molecular breast imaging
      (MBI) can reliably detect tumors <2 cm in diameter. This study extends our work
      to a larger patient population and examines the technical factors that influence
      the ability of MBI to detect small breast tumors. Following injection of 740 MBq
      Tc-99m sestamibi, MBI was performed on 100 patients scheduled for biopsy of a
      lesion suspicious for malignancy that measured <2 cm on mammography or
      sonography. Using a small field of view gamma camera, patients were imaged in the
      standard mammographic views using light pain-free compression. Subjective
      discomfort, breast thickness, the amount of breast tissue in the detector field
      of view, and breast counts per unit area were measured and recorded. Follow-up
      was obtained in 99 patients; 53 patients had 67 malignant tumors confirmed at
      surgery. Of these, 57 of 67 were detected by MBI (sensitivity 85%). Sensitivity
      was 29%, 86%, and 97% for tumors <5, 6-10, and > or =11 mm in diameter,
      respectively. In seven patients, MBI identified eight additional mammographically
      occult tumors. Of 47 patients with no evidence of cancer at biopsy or surgery,
      there were 36 true negative and 11 false positive scans on MBI. MBI has potential
      for the regular detection of malignant breast tumors less than 2 cm in diameter.
      Work in progress to optimize the imaging parameters and technique may further
      improve sensitivity and specificity.

PMID- 17214788
TI  - Supraclavicular nodal failure in patients with one to three positive axillary
      lymph nodes treated with breast conserving surgery and breast irradiation,
      without supraclavicular node radiation.
AB  - The purpose of this study was to evaluate the risk factors associated with
      supraclavicular nodal failure (SCF) in patients with one to three positive
      axillary nodes treated with breast conserving surgery and axillary dissection
      without supraclavicular node radiation (S/C RT) to aid in the selection of
      patients for S/C RT. Two hundred two breast conservation patients with one to
      three positive axillary nodes on axillary dissection treated with breast
      irradiation without S/C RT and 20 patients with S/C RT between August 1985 and
      May 2002 were identified and retrospectively evaluated. The Kaplan-Meier method
      was used to determine SCF-free and overall survival curves. Risk factors for SCF
      were examined. The median follow-up from surgery was 72 months (range: 4-195).
      Nine of 202 patients (4%) failed in the ipsilateral breast, 4 (2%) in the
      ipsilateral supraclavicular lymph nodes, 4 (2%) in the ipsilateral axillary
      and/or internal mammary nodes and 30 (15%) distantly. The 5- and 10-year SCF-free
      survival was 97.92%. The overall survival at 5, 10, and 15 years was 91.35%,
      75.58%, and 67.18%, respectively. SCFs were associated with high grade or ER
      negative cancers, but not with number of positive nodes. Two of the four SCFs
      were associated with distant metastases, and two with local failures. One patient
      with a SCF was salvaged and is disease-free at 134 months. The overall low
      incidence of SCF in patients with one to three positive nodes treated with breast
      radiation alone after breast conserving surgery and adequate axillary dissection
      suggests that additional S/C RT is unnecessary in this cohort. When it occurs,
      supraclavicular nodal failure is often associated with distant metastases.

PMID- 17214789
TI  - Are tri-ethnic low-income women with breast cancer effective teachers of the
      importance of breast cancer screening to their first-degree relatives? Results
      from a randomized clinical trial.
AB  - The purpose of this study was to determine the efficacy of women with breast
      cancer as teachers of the importance of breast cancer screening to their first
      degree female relatives. The sample was restricted to low-income working age
      women recruited from four hospitals. The study design was a randomized clinical
      trial. At each hospital, breast cancer patients (probands) were randomized into
      one of two study groups: (i) intensive, individual educational training on breast
      cancer screening or (ii) standard clinic education on breast cancer screening.
      The probands were instructed to teach at least one of their first-degree female
      relatives (21+ years of age) about breast cancer screening techniques. Three to
      six months after the enrollment of the probands, their relatives were contacted
      by telephone to determine breast cancer screening practices. A total of 79
      probands and 96 relatives participated in the study. Relatives in the education
      group when compared with the control group were: 1.25 times more likely to have
      clinical breast examination (p = 0.005), 2.83 times more likely to have scheduled
      a clinical breast examination (p = 0.046), and, 1.36 times more likely to have
      been told about performing breast self-examination (p = 0.05). Additionally,
      relatives in the education group were more likely to have received a pamphlet on
      breast cancer screening (RR = 1.58, p = 0.009) and have discussed the importance
      of breast cancer screening (RR = 1.33, p = 0.020) from the proband. Special
      education training did not impact mammography utilization of the relatives. From
      these findings, a tri-ethnic group of low-income women with breast cancer can be
      effective teachers of breast cancer screening practices, at least for promoting
      clinical breast examination and transmitting messaging for performance of breast
      self-examination if given the adequate training.

PMID- 17214790
TI  - Aromatase inhibitors in the adjuvant treatment of postmenopausal women with early
      breast cancer: Putting safety issues into perspective.
AB  - Tamoxifen has been the gold standard adjuvant therapy for the treatment of
      postmenopausal women with hormone-receptor-positive (HR+) early breast cancer for
      many years. Tamoxifen treatment is limited to 5 years because of the development
      of de novo and acquired resistance, and an ongoing risk of adverse events,
      including endometrial cancer, thromboembolic events, and gynecological symptoms
      with long-term use. The third-generation aromatase inhibitors (AIs), letrozole,
      anastrozole, and exemestane, are displacing tamoxifen as the first-choice therapy
      for HR+ early breast cancer, and are now recommended as the preferred therapy by
      national and international guidelines. Recent randomized trials have demonstrated
      that the AIs are more effective than tamoxifen in preventing disease recurrence
      when used in substitution and sequential strategies in the early adjuvant
      setting, and letrozole has been shown to be more effective than placebo in the
      extended adjuvant setting (after 5 years of tamoxifen therapy). Trial safety data
      show that the overall tolerability of AIs is similar to that of tamoxifen, with
      adverse events being predictably characteristic of estrogen deprivation; however,
      some important differences in adverse event profiles between tamoxifen and the
      AIs have been demonstrated. In addition to antiestrogenic effects, tamoxifen acts
      as an estrogen agonist in some tissues, which can lead to serious side effects
      not associated with the AIs, which prevent estrogen biosynthesis. A lower
      incidence of gynecological and thromboembolic events is observed in patients
      taking AIs, and fewer cases of endometrial cancer are seen compared with
      tamoxifen. Adverse events that are more frequent with adjuvant AI therapy
      compared with tamoxifen include arthralgia and myalgia, bone loss, and effects on
      the cardiovascular system and blood lipids. The effects of AIs on bone are
      predictable and may be easily managed, where necessary, with bisphosphonates.
      Studies examining the effects of AIs on the cardiovascular system and lipid
      profiles, including in the extended adjuvant setting, suggest that these adverse
      events may be due to the absence of a protective effect of tamoxifen rather than
      true AI toxicity. Further studies are required to determine the long-term safety
      of AI therapy in postmenopausal women with HR+ early breast cancer.

PMID- 17214791
TI  - Multicenter evaluation of a new ultrasound-guided biopsy device: Improved
      ergonomics, sampling and rebiopsy rates.
AB  - The purpose of this study was to evaluate performance, ergonomics, and immediate
      rebiopsy rate of a new vacuum-assisted biopsy (VAB) device for ultrasound-guided
      breast biopsies. Between December 2002 and April 2003, 113 patients meeting study
      criteria were biopsied at four centers using the new 9 gauge VAB device. The
      device has a radiofrequency-tipped probe, 360 degrees vacuum, a circumferential
      cutter, and a coaxial cannula for multiple sampling. Patient and procedural data
      included breast composition, lesion characteristics, number of samples, procedure
      time, and complications. Quality of samples, lesion access, and ergonomic
      features were assessed qualitatively and compared with prior experience with
      other biopsy devices. Immediate rebiopsy rate included high-risk lesions
      requiring surgical excision (obligate rebiopsy) and lesions requiring rebiopsy
      due to discordance or insufficient samples yielding nondiagnostic material. Data
      were analyzed using the Wilcoxon signed-rank test. One hundred thirteen patients
      aged 20-83 years (mean 52) were successfully biopsied with dense/fibrous breast
      tissue in 60% and dense/fibrous lesions in 49%. Lesions measured 6-63 mm (mean
      17); 97% were masses. Five circumferential specimens (range 2-19) were obtained
      in 6 minutes (range 2-20). Operators rated safety and comfort comparable with
      existing devices and rated sample quality, breast/lesion penetration, and
      positioning ease/accuracy superior (p < 0.01). Diagnoses included 37 cancers, 70
      benign, and six high-risk lesions with one upgrade from atypical ductal
      hyperplasia to ductal carcinoma in situ at surgery. Excluding obligate excision
      in high-risk diagnoses, the immediate rebiopsy rate was 2%. No complications
      required intervention. The new VAB device provides diagnostic samples and reduces
      sampling error defined by immediate rebiopsy rate. Compared with other devices,
      it is more ergonomic to target and position for sampling, particularly in dense
      breast tissue or lesions.

PMID- 17214792
TI  - New antineoplastic agent, MK615, from UME (a Variety of) Japanese apricot
      inhibits growth of breast cancer cells in vitro.
AB  - MK615 is an extract mixture containing hydrophobic substances from Japanese
      apricot. In this study, the antineoplastic effects of MK615 against breast cancer
      cells were investigated. Two breast cancer cell lines, MDA-MB-468 (MDA) and MCF7,
      were cultured with (600, 300, and 150 mug/mL) or without MK615. After 72 hours of
      incubation, growth inhibition was evaluated by MTT assay. The cells were then
      cultured with MK615 (300 mug/mL) and morphological changes were studied by light
      and electron microscopy. Finally, the mechanism of the antineoplastic effect of
      MK615 was evaluated by cell cycle and apoptosis assay. MK615 inhibited the growth
      of MDA and MCF7 in a dose-dependent manner. The percentage growth inhibition of
      MDA at dosages of 600, 300, and 150 mug/mL was 59.2%, 52.4%, and 23.3%,
      respectively, and that for MCF7 was 83.5%, 52.7%, and 16.6%, respectively.
      Morphological changes after MK615 treatment included massive vacuolization in the
      cytoplasm and apoptotic changes in the nucleus. These changes began to be
      apparent after at least 6 hours of incubation. Cell cycle analysis showed that
      MK615 increased the proportion of cells in the G2-M phase in both MDA (7.8-11.7%)
      and MCF7 (8.1-18.7%), and finally both cell lines became apoptotic. The
      proportion of apoptotic cells increased with incubation time. MK615 effectively
      inhibits the growth of breast cancer cells in vitro, possibly by cell cycle
      modification and apotosis induction. MK615 should be further investigated as a
      promising anti-breast cancer agent.

PMID- 17214793
TI  - Utility of the free deep inferior epigastric perforator flap in chest wall
      reconstruction.
AB  - Breast cancer chest wall recurrence is often treated with chemotherapy, radical
      surgery, and radiation. Extensive chest wall resection requires soft-tissue
      reconstruction with tissue that provides chest wall stability and durability for
      additional radiation. Local and regional muscle and musculocutaneous flaps are
      often used for reconstruction. Free flaps, such as the transverse rectus
      abdominis musculocutaneous flap, are used for large defects, although donor site
      morbidity can result. The free deep inferior epigastric perforator (DIEP) flap
      provides coverage for large defects and may have less donor site morbidity. We
      describe the use of the free DIEP flap to reconstruct large chest wall defects
      (mean, 501 cm2 defects) after the resection of recurrent breast cancer in two
      patients. One patient had 2% flap loss. No donor site morbidity occurred. The
      free DIEP flap is a durable and reliable flap that provided immediate and
      complete coverage of these large chest wall defects with no donor site morbidity
      and did not delay the administration of adjuvant therapy.

PMID- 17214794
TI  - Should the extent of lobular neoplasia on core biopsy influence the decision for
      excision?
AB  - The purpose of this study was to determine whether there is a criterion that can
      be utilized to determine if excisional biopsy is indicated following the
      diagnosis of lobular neoplasia (LN) on core biopsy. Retrospective review of
      patient records with diagnosis of LN as highest risk diagnosis on core biopsy was
      performed. LN was defined to include both atypical lobular hyperplasia (ALH) and
      lobular carcinoma in situ (LCIS) and was categorized as focal or diffuse. The
      pathology was correlated with the mammographic finding to determine whether the
      diagnosis of LN was incidental or related to the mammographic finding. For those
      patients who did not undergo excision, follow-up data are presented along with
      treatment information. A total of 4,555 breast core biopsies were performed at
      our institution from January 1997 through March 2005. Of these, 35 patients were
      diagnosed with LN. Twenty six (74%) went on to excision and nine (26%) were
      followed. Biopsy was recommended for mammographically detected calcifications in
      the majority of cases. Twenty four (92%) of the 26 excised cases had focal LN and
      2 of 26 (8%) had diffuse LN. Infiltrating lobular carcinoma was diagnosed in both
      cases of diffuse LN and no infiltrating carcinoma was seen when focal LN was
      diagnosed on core. Excision may not be necessary when a diagnosis of only focal
      LN is made on core biopsy. Diffuse LN may indicate an associated invasive cancer
      and should prompt excision.

PMID- 17214795
TI  - The effects of breast augmentation surgery on future ability to lactate.
AB  - The majority of women receiving breast augmentation surgery do so at a time in
      their lives when both reproduction and lactation are common. It does not occur to
      most women to consider the possible effects breast augmentation surgery may have
      on their future ability to exclusively breast-feed their baby. Most women raise
      concerns about their inability to exclusively breast-feed years after surgery
      when they have a child. It is therefore important that women considering breast
      augmentation surgery be fully informed of the possible effects surgery may have
      on their future ability to lactate. The possible direct effects of surgery on the
      breast tissue and the complications of breast surgery on future ability to
      lactate are discussed. Surgical technique, i.e., implant type and placement, are
      also discussed. The types of incisions made into the breast tissue and the
      positioning of the implants once inside the breast parenchyma are analyzed and
      their possible effects on future ability to lactate are explored. Women who
      undergo breast augmentation surgery have a greater incidence of lactation
      insufficiency. Factors directly related to the surgical procedure as well as
      short- and long-term complications of surgery compromise future ability to
      exclusively breast-feed a baby. Factors directly related to surgery include
      severing of the lateral and medial branches of the fourth intercostal nerve or
      the nerve endings of the nipple-areolar complex, which, lead to reduced sensation
      and loss of the suckling reflex resulting in decreased milk production. Hematoma
      formation increases the risk of developing capsular contracture therefore
      necessitating the need for further surgical intervention. Infection also requires
      further intervention and as a result, further risk to the breast tissue. Long
      term breast pain, capsular contracture, and pressure effects on the breast from
      the implant are all possible long-term complications that compromise a woman's
      future ability to lactate and exclusively breast-feed her baby. With good
      surgical technique and proper postoperative management, most of the complications
      associated with surgery that may result in insufficient milk production can be
      minimized but not always avoided. Compared with nonaugmented women, women who
      have had augmentation surgery have a higher incidence of lactation insufficiency.

PMID- 17214796
TI  - Tumor size and lymph node status in multifocal breast cancer.
AB  - Tumor size correlates with lymph node metastasis in breast cancer. In multifocal
      lesions there is controversy about considering the summation of the largest
      diameter of each tumor. A total of 122 patients with multifocal breast cancer
      were compared in a retrospective study with 177 patients with unifocal tumors,
      correlating tumor size with lymph node metastasis. In multifocal tumors, two
      sizes were considered: the diameter of the largest tumor and the combined
      diameter of all lesions. Relationship was established by three different logistic
      models using variables such as age, number of lesions, histologic type, and
      grade. At a same size of the largest diameter of a unifocal or multifocal lesions
      and the combined diameter of a multifocal lesion, the latter shows less
      probability of nodal metastasis indicating that combined diameter is an
      overestimation of the lesion size. Our results indicate that in multifocal breast
      cancer, only the diameter of the largest tumor breast cancer has relationship
      with lymph node metastasis.

PMID- 17214797
TI  - Novel clinical trial designs for treatment of ductal carcinoma in situ of the
      breast with trastuzumab (herceptin).
AB  - Because ductal carcinoma in situ (DCIS) avidly expresses Her2/neu, the target of
      the monoclonal antibody trastuzumab, and because trastuzumab has been shown to be
      effective against invasive breast cancer, trastuzumab may be effective for
      reducing the tumor burden and abrogating or reversing the hypothesized transition
      from in situ to invasive disease in patients with DCIS. To test this hypothesis,
      a trial of neoadjuvant trastuzumab for DCIS has been opened at our institution.
      Because trastuzumab has been shown to act as a radiosensitizing agent for
      Her2/neu-overexpressing cancer and because there are currently no systemic
      treatments for estrogen-receptor-negative DCIS, it makes sense to investigate
      whether use of trastuzumab concurrently with postoperative radiation therapy
      improves local control of DCIS. The National Surgical Adjuvant Breast and Bowel
      Project (NSABP) is planning a trial to test this hypothesis. The risk of cardiac
      toxicity associated with the doses of trastuzumab planned for these trials
      (cumulative doses of 8 mg/kg for our trial and 14 mg/kg in the NSABP trial) is
      believed to be minimal, but the safety profile of these approaches will need to
      be closely monitored.

PMID- 17214798
TI  - The use of a deep inferior epigastric perforator flap (DIEP) in a case of severe
      breast asymmetry secondary to radiation therapy during childhood.
AB  - Breast radiotherapy during childhood may cause unpredictable outcomes in soft
      tissue growth and may be responsible for most iatrogenic-related breast
      hypoplasias. Poor local skin quality and subcutaneous atrophy poses a difficult
      problem for the use of alloplastic tissues. Clinical use of a deep inferior
      epigastric perforator flap (DIEP) in oncological breast surgery is a common
      practice; however few studies have described its application in benign situations
      and no previous report addressed this subject. The authors indicate the use of
      the DIEP flap to correct severe hypomastia after previous childhood radiotherapy
      for hemangioma treatment, followed by unsuccessful alloplastic tissue
      reconstruction. For selected patients the DIEP flap may constitute a new
      alternative for complications of radiotherapy treatment due to the possibility of
      large tissue transfer with minimal donor area morbidity. The quantity of flap
      tissue necessary to restore the breast mound, the perforator vessel size, and the
      quality of suitable recipient vessels should be carefully evaluated. However, the
      need for microsurgical training as well as the extended surgical time are the
      main limiting factors for the use of this flap.

PMID- 17214799
TI  - Modified wise pattern skin reduction for plexiform neurofibromatosis of the
      breast.
AB  - Von Recklinhausen's neurofibromatosis is an autosomal dominant condition
      occurring typically with cafe au lait patches, axillary freckling, multiple
      fibromata, and Lisch nodules. We present a case of a 36-year-old female who
      presented with severe neurofibromatosis involving the lower half of the breast.
      The patient was not keen on mastectomy and pedicle flap reconstruction. A
      modified wise pattern incision was employed to remove the lower half of the
      breast and neurofibromatosis leading to a reasonable result.

PMID- 17214800
TI  - Myoid hamartoma of the breast: a case report and review of the literature.
AB  - Myoid hamartomas of the breast are extremely rare breast lesions, with a poorly
      understood pathogenesis. A 60-year-old woman presented with a palpable mass in
      the right breast. Breast ultrasonography and mammography showed the presence of a
      breast lesion with benign characters, but were not diagnostic. A local excision
      of the mass was performed; histology revealed that the tumor was composed of
      epithelial and stromal cells. Histological and immunohistochemical findings
      established the diagnosis of myoid hamartoma. The patient is well 4 years later
      without tumor recurrence. Breast myoid hamartomas are exceptionally rare benign
      lesions; complete surgical excision achieves cure.

PMID- 17214801
TI  - Breast myxoma: Radiologic and histopathologic features.
AB  - Myxomas are benign mesenchymal tumors, which rarely develop in the breast.
      Histologically, stellate, round, and spindle-shaped cells with vesicular nuclei
      and scant cytoplasm are scattered in the myxoid stroma. We present a case of this
      rare type of breast tumor with sonographic and mammographic findings.

PMID- 17214802
TI  - Giant apocrine hidradenoma of the breast.
AB  - We report a case of a 26-year-old woman with an 8.0-cm tumor of the left breast.
      The tumor was clinically and radiologically suspicious for malignancy. The
      pathologic evaluation of the core biopsy and the subsequent excision specimen
      revealed a benign sclerosing, cystic, and papillary adnexal tumor with apocrine
      and clear cell morphology. The immunohistochemical staining for p63 was positive.
      Estrogen, progesterone, and Her-2 receptor immunohistochemical stains were
      negative. The cytogenetic analysis revealed 46, XX t(11:19) (q21;q13.1) balanced
      translocation. The final diagnosis was apocrine hidradenoma.

PMID- 17214803
TI  - Breast cancer metastasized to the scalp mimicking alopecia areata: Alopecia
      neoplastica.

PMID- 17214804
TI  - Florid papillomatosis: A rare cause of bilateral giant breast lumps in the
      elderly.

PMID- 17214805
TI  - Isolated breast involvement at recurrence in a child with T-cell lymphomas.

PMID- 17214806
TI  - Sarcoidosis of the breast: An unusual presentation of a systemic disease.

PMID- 17214807
TI  - Exposure during open breast surgical procedure.

PMID- 17214808
TI  - Pleomorphic adenoma of the breast.

PMID- 17214809
TI  - Possibility of radiotherapy-associated cardiovascular side effects in breast
      cancer patients by modern radiotherapy techniques.

PMID- 17214810
TI  - Touch prep cytology as a preferred approach for evaluating sentinel lymph nodes
      in breast cancer.

PMID- 17214811
TI  - Octreotide can control lymphorrhea after axillary node dissection in mastectomy
      operations.

PMID- 17214812
TI  - Therapeutic options for Paget's disease: A single institution long-term follow-up
      study.

PMID- 17214814
TI  - An anatomic study of the calcaneal bursae in the horse.
AB  - OBJECTIVES: To establish an injection site for the gastrocnemius calcaneal bursa
      (GCB), to identify communication patterns between the calcaneal bursae, to
      estimate the proximal and distal extents of the intertendinous calcaneal bursa
      (ICB) and to identify variations from previous anatomic descriptions. STUDY
      DESIGN: Descriptive anatomic study. ANIMALS: Cadaveric equine hindlimbs (n=18)
      from 9 adult horses. METHODS: Communication between the ICB and GCB was
      determined in 18 cadaveric hindlimbs by injection of a latex mixture, followed by
      examination of sequential sagittal sections and documentation of the distribution
      of the latex mixture and communication sites. The distal and proximal extents of
      the ICB and subcutaneous calcaneal bursa (SCB), relative to the tuber calcanei
      (TC) were recorded. RESULTS: Communication between the ICB and the GCB was
      confirmed on the medial and lateral aspect in 100% and 50% of limbs,
      respectively. Communication between the SCB and the ICB, and therefore the GCB,
      was identified in 39% of limbs. Plantar reflections of the ICB existed in 33% of
      limbs. Mean extent of the ICB relative to the TC was 7.0 cm distally and 9.6 cm
      proximally. The SCB often occupies a more distal position than previously
      reported. CONCLUSIONS: The ICB and the GCB should be considered 1 synovial
      structure with 2 communicating compartments. CLINICAL RELEVANCE: The GCB may be
      an alternative site for synoviocentesis when there is septic calcaneal bursitis.
      Improved knowledge of calcaneal bursae anatomy may aid in diagnosis and treatment
      of lesions involving these structures.

PMID- 17214815
TI  - Use of capecitabine to prevent acute renal allograft rejection in dog erythrocyte
      antigen-mismatched mongrel dogs.
AB  - OBJECTIVE: To assess efficacy and toxicity of a capecitabine (CAP)-based regimen
      for preventing rejection of renal allografts in dog erythrocyte antigen (DEA)
      mismatched mongrel dogs. STUDY DESIGN: Prospective, pilot study. ANIMALS: Eight
      healthy, unrelated, DEA mismatched, adult mongrel dogs. METHODS: All dogs
      received CAP, starting at 50 mg/m2 PO b.i.d. 4 days preoperatively, increasing to
      200 mg/m2 PO b.i.d. by the day of surgery. All dogs received cyclosporine-A (CsA)
      and prednisolone starting 2 days preoperatively. Standard heterotopic renal
      transplantation with native nephrectomy was performed. After 90 days, surviving
      dogs were euthanatized and histopathologic examination was performed. RESULTS:
      Two of 8 dogs developed acute neurotoxicity leading to death or euthanasia within
      5 days of surgery. For the 6 remaining dogs, there were no statistically
      significant changes in complete blood count or serum biochemical values. No
      opportunistic infections developed during the study period. Five of 6 dogs had no
      to minimal evidence of graft rejection. Two of 6 dogs developed superficial and
      pigmentary keratitis. Significant histopathologic findings in all dogs included
      mild lymphoplasmacytic gastroenteritis, steroid hepatopathy, and corneal
      epithelial thinning. One dog had moderate interstitial nephritis and pyelitis.
      CONCLUSIONS: In this experimental model, a CAP-CsA-prednisolone immunosuppressive
      regimen was effective in preventing rejection of allografts in DEA-mismatched
      dogs. Severe, unpredictable neurotoxicity and variable ocular toxicity
      significantly limit clinical applications at this time. CLINICAL RELEVANCE: A CAP
      CsA-prednisolone protocol is an effective, oral immunosuppressive regimen for
      prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical
      application, identification of patients susceptible to toxic side effects would
      be necessary.

PMID- 17214816
TI  - Surgical management of left-divisional intrahepatic portosystemic shunts: outcome
      after partial ligation of, or ameroid ring constrictor placement on, the left
      hepatic vein in twenty-eight dogs (1995-2005).
AB  - OBJECTIVES: To evaluate outcome in dogs with left divisional intrahepatic
      portosystemic shunts (PSS) treated by partial ligation (PL) or ameroid ring
      constrictor (ARC) placement on the left hepatic vein. DESIGN: Retrospective
      study. ANIMALS: Dogs (n=28) with left divisional intrahepatic PSS. METHODS:
      Retrieved data from medical records of dogs with left divisional intrahepatic PSS
      that had PL (n=17) or ARC (n=11) were signalment, history, clinical signs,
      preoperative blood work, portal pressure measurements, ARC size, complications
      and postoperative technetium scintigraphy. Outcome assessed by owner interview 6
      months-10 years after surgery was classified as excellent, good or poor.
      Differences were tested by exact chi2 test. RESULTS: Major complications occurred
      in 3 dogs: coagulopathy (1 PL dog died), ascites (1 PL dog survived) and seizures
      (1 ARC dog died). Eight PL dogs had technetium portal scintigraphy; 1 dog was
      negative and 7 dogs positive for persistent shunting. Seven ARC dogs had
      scintigraphy; 4 dogs were negative and 3 positive for persistent shunting. In PL
      dogs, long-term clinical outcome was excellent (92%) or good (8%) whereas, in ARC
      dogs it was excellent (20%), good (50%) or poor (30%). This outcome difference
      between treatment groups was significant (P=.0012). CONCLUSION: Dogs treated by
      PL had significantly better long-term outcome compared with ARC treated dogs.
      CLINICAL RELEVANCE: Based on these data, ARC placement on the left hepatic vein
      in dogs with left-divisional intrahepatic PSS cannot be recommended.

PMID- 17214817
TI  - Epidemiologic factors associated with the anatomic location of intrahepatic
      portosystemic shunts in dogs.
AB  - OBJECTIVE: To determine whether breed, sex, country of origin, and age are
      associated with anatomic location of intrahepatic portosystemic shunts (IHPSS) in
      dogs. STUDY DESIGN: Multi-institutional retrospective case series. SAMPLE
      POPULATION: Dogs (n=125) with IHPSS from the veterinary teaching hospitals of the
      University of Florida (21), Sydney University (44), and the University of
      California-Davis (60). METHODS: Dogs with surgical/necropsy confirmation of
      single IHPSS were identified. Data were analyzed using logistic regression for
      associations between age, breed, sex, and country with the anatomic location of
      IHPSS. RESULTS: Right (34%), left (34%), and central divisional IHPSS (32%) were
      prevalent with approximately equal frequency in Australia; in the United States,
      the prevalence of right (24%) and central divisional (26%) combined was similar
      to left divisional IHPSS (51%). Country (P=048), sex (P=.016), and Australian
      cattle dog ([ACD], P=.025) were significantly associated with IHPSS location.
      Dogs in Australia had 2.5-fold higher odds of having right versus left divisional
      IHPSS. Males and ACD had 2.8- and 5.6-fold higher odds of having right versus
      left divisional IHPSS. Australian dogs were significantly older than those in the
      United States (P<.0001) and ACD were significantly older than other breeds
      (P=.0067). CONCLUSIONS: Although country of origin, breed, and sex had
      significant associations with anatomic location of IHPSS, signalment does not
      appear to be a strong predictor of shunt location when used alone. CLINICAL
      RELEVANCE: For the common breeds in this report, signalment is only occasionally
      helpful in predicting likelihood of anatomic division in IHPSS. Australian cattle
      dogs and male dogs have a statistical association with right (versus left)
      divisional IHPSS. If advanced imaging techniques are not available, veterinary
      surgeons should be prepared to locate and address any anatomic configuration of
      IHPSS in a dog.

PMID- 17214818
TI  - Incidence of pulmonary embolism after non-cemented total hip arthroplasty in
      eleven dogs: computed tomographic pulmonary angiography and pulmonary perfusion
      scintigraphy.
AB  - OBJECTIVE: To compare the incidence of pulmonary embolism (PE) in 11 dogs that
      had non-cemented total hip replacement (THR) to that reported in dogs after
      cemented THR. STUDY DESIGN: Prospective clinical study. ANIMALS: Large mixed
      breed dogs (n=11). METHODS: Thoracic computed tomographic pulmonary angiography
      (CTA) was performed on all dogs pre- and postoperatively. Pulmonary perfusion
      scintigraphy was performed postoperatively. RESULTS: PE was not identified on
      postoperative CTA or pulmonary perfusion scintigraphy. CONCLUSIONS: The incidence
      of PE after non-cemented THR in these 11 dogs, as evaluated with pulmonary
      perfusion scintigraphy and thoracic CTA was lower than reported in dogs
      undergoing cemented THR. CLINICAL RELEVANCE: Based on the results of this study
      the incidence of PE as a complication of total hip arthroplasty is reduced when a
      non-cemented system is used.

PMID- 17214819
TI  - Retrospective comparison of surgical ligation and transarterial catheter
      occlusion for treatment of patent ductus arteriosus in two hundred and four dogs
      (1993-2003).
AB  - OBJECTIVE: To compare procedure time, complications, mortality, and short-term
      outcome in dogs with patent ductus arteriosus (PDA) treated by surgical ligation
      (SL) or transarterial coil occlusion (TCO). STUDY DESIGN: Retrospective study.
      ANIMALS: Dogs with PDA (n=204). METHODS: Medical records of dogs treated for PDA
      were reviewed. Dogs treated by SL when it was the primary method used for PDA
      treatment (1993-1998) were compared with dogs treated by TCO when it was the
      primary method used for PDA treatment (1999-2003). Dogs treated during the
      transition between techniques, dogs treated with SL (1999-2003) and dogs treated
      with TCO before 1999, as well as dogs with pulmonary hypertension, or
      bidirectional or reversed (right-to-left) flow through the PDA were excluded from
      analysis. RESULTS: Age, weight, gender distribution, and procedure times (P=.43)
      were similar for both groups. Major complications were more common with SL (12%
      versus 4.3%; P=.035) whereas minor complications were more common with TCO (12%
      versus 26%; P=.015). Initial success rate was higher for SL (94%) compared with
      TCO (84%; P=.027). There was no significant difference in mortality between SL
      (5.6%) and TCO (2.6%; P=.27). CONCLUSIONS: Both SL and TCO are acceptable PDA
      treatments with comparable mortality; however, SL was associated with a higher
      risk of major complications and TCO was associated with a lower initial success
      rate.

PMID- 17214820
TI  - Histologic comparison of canine skin biopsies collected using monopolar
      electrosurgery, CO2 laser, radiowave radiosurgery, skin biopsy punch, and
      scalpel.
AB  - OBJECTIVE: To compare the histologic appearance of canine skin biopsies collected
      by use of a scalpel, skin biopsy punch, monopolar electrosurgery, CO2 laser, and
      radio wave radiosurgery in fully rectified wave form (RWRS). STUDY DESIGN:
      Experimental, randomized design. ANIMALS: Healthy adult grayhounds (n=4).
      METHODS: Skin biopsies were collected using 5 techniques. Cut margins of biopsy
      specimens and adjacent peripheral skin were evaluated using light microscopy to
      compare penetration of the dermis by tissue carbonization (char). RESULTS: No
      char occurred in skin specimens collected by biopsy punch and scalpel. Char
      penetration occurred in all specimens collected by electrosurgery, CO2 laser, and
      RWRS. Mean char penetration in skin biopsies collected by RWRS (0.158 mm) was
      significantly less than for monopolar electrosurgery (0.223 mm) and CO2 laser
      (0.215 mm). Mean char penetration in adjacent peripheral skin surrounding
      biopsies collected by RWRS (0.171 mm) was significantly less than monopolar
      electrosurgery (0.255 mm) but not less than CO2 laser (0.215 mm, P<.07).
      CONCLUSIONS: RWRS (blended waves in cut-coagulate mode) caused less lateral
      thermal damage to canine skin biopsies than monopolar electrosurgery and CO2
      laser and less lateral thermal injury to peripheral skin than monopolar
      electrosurgery. CLINICAL RELEVANCE: Excision of canine skin biopsies with heat
      generating devices may not allow reliable histologic interpretation, particularly
      when assessing margins of small biopsy specimens. RWRS may be less traumatic to
      canine skin than monopolar electrosurgery and CO2 laser when used to make
      incisions.

PMID- 17214821
TI  - Effect of intrathecal amikacin administration and repeated centesis on digital
      flexor tendon sheath synovial fluid in horses.
AB  - OBJECTIVE: To determine the effect of intrathecal amikacin administration and
      repeated tenovaginocentesis on the total nucleated cell count (TNCC), total
      protein (TP) concentration and cytologic characteristics of synovial fluid of the
      equine digital flexor tendon sheath (DFTS). STUDY DESIGN: Randomized, cross-over
      experimental design. ANIMALS: Adult horses (n=8). METHODS: Synovial fluid was
      aseptically collected from the DFTS and either 1 mL amikacin sulfate (250 mg/mL)
      or lactated Ringer's solution (LRS) was injected into the DFTS. Serial synovial
      fluid samples were obtained at 0, 12, 24, 48, and 72 hours. The opposite
      treatment was administered to the contralateral DFTS after a washout period of 2
      weeks. RESULTS: Treatment increased TP concentration, TNCC, percentage of
      neutrophils, and neutrophil counts from baseline levels. There was no difference
      between treatment of the DFTS with amikacin or LRS. Values peaked at 12-24 hours
      after the initial centesis and then declined toward baseline levels. CONCLUSIONS:
      Injection and repeat centesis of the normal DFTS with 250 mg amikacin or an
      equivalent volume of LRS resulted in mild increases in synovial fluid analytes
      from baseline. Synovial inflammation in this study was not accompanied by
      lameness at the walk and measured analytes returned toward baseline levels within
      12-24 hours of first injection. CLINICAL RELEVANCE: The effect of
      tenovaginocentesis and intrathecal administration of amikacin or LRS on DFTS
      synovial fluid values are modest in most horses; however, some horses can develop
      marked increases in synovial fluid values that may be interpreted as sepsis.

PMID- 17214822
TI  - In vitro bursting pressures of jejunal enterotomy closures in llamas.
AB  - OBJECTIVE: To evaluate closure strength (in vitro bursting pressure) of jejunal
      enterotomies in llamas. STUDY DESIGN: In vitro experimental study. SAMPLE
      POPULATION: Jejunal specimens (n=72) from 6 llamas. METHODS: Differences in
      bursting pressures and luminal diameters were compared between 2 layer enterotomy
      closures with an initial full thickness simple continuous pattern oversewn with
      either a continuous Lembert or Cushing suture pattern using 3 sizes (2-0, 3-0, 4
      0) of polyglactin 910 and polydioxanone. RESULTS: Bursting pressures were
      significantly higher for enterotomies closed with polydioxanone than polyglactin
      910, independent of suture size, but there was no difference between Lembert and
      Cushing oversew patterns. Use of a Lembert pattern reduced intestinal diameter
      more than a Cushing pattern regardless of suture material or size. CONCLUSIONS:
      Although polydioxanone resisted higher bursting pressures than polyglactin 910,
      both suture materials should be considered satisfactory for jejunal enterotomy
      closure in llamas based on typical intraluminal pressures expected in clinical
      patients. The optimal oversew pattern may be continuous Cushing to maximize the
      luminal diameter in small intestinal enterotomy closures. CLINICAL RELEVANCE: In
      vitro bursting pressures may help to predict which enterotomy sites would leak
      post-operatively, although further studies are necessary to determine the outcome
      in clinical patients.

PMID- 17214823
TI  - Humerus fractures in llamas and alpacas: seven cases (1998-2004).
AB  - OBJECTIVE: To describe treatment and outcome of humerus fractures in llamas and
      alpacas. STUDY DESIGN: Retrospective study. ANIMALS: Llamas (n=4) and alpacas (3)
      with humerus fracture. METHODS: Medical records (January 1, 1998-August 1, 2004)
      were reviewed for small camelids with a humeral fracture. Retrieved data were
      signalment, history, physical examination and radiographic findings, surgical and
      medical treatment, and outcome. RESULTS: Humeral fracture occurred in 7 of 38
      (18%) camelids admitted with fractures. Affected animals were aged from 1 month
      to 3 years old. Fracture configuration included long-oblique (n=4), short-oblique
      (2), and Salter-Harris Type II fracture of the proximal physis (1). One adult
      llama was managed by stall confinement and surgical repair was attempted in the
      other camelids: fixation by screws inserted in lag fashion (n=3), intramedullary
      pinning and fixation by screws inserted in lag fashion (1), rush pinning (1), and
      bone plating (1). A Velpeau sling was used for additional support in 3 animals.
      All fractures healed but temporary radial nerve paresis occurred in 3 animals.
      Limb shortening and permanent lameness occurred in the llama managed
      conservatively. CONCLUSIONS: Humerus fractures in small camelids are amenable to
      surgical repair which may offer better long-term outcome than medical treatment
      alone. CLINICAL RELEVANCE: Surgical treatment of humerus fractures should have a
      good prognosis in llamas and alpacas. In select cases, minimally invasive
      techniques, such as rush pinning or fixation by screws inserted in lag fashion
      are sufficient for fracture healing.

PMID- 17214824
TI  - Pinhole castration: a novel minimally invasive technique for in situ spermatic
      cord ligation.
AB  - OBJECTIVE: To describe a minimally invasive technique for castration of bull
      calves by in situ ligation of the spermatic cord. STUDY DESIGN: Experimental
      study. ANIMALS: Male calves (n=6) aged, 48-56 days. METHODS: Calves were blocked
      by weight and then separated into 3 groups: (1) bilateral spermatic cord
      ligation; (2) unilateral-1 spermatic cord ligated; and (3) control-neither
      spermatic cord ligated. After local anesthesia, in situ spermatic cord ligation
      was achieved by restraining the cord laterally within the scrotal sac and passing
      suture through a hypodermic needle inserted caudal to cranial at the neck of the
      scrotum and adjacent the medial margin of the restrained spermatic cord. The
      needle was removed leaving the suture in place and the spermatic cord
      repositioned medially, then the needle was reinserted through the original holes
      and the suture passed back through the needle, which was withdrawn. The suture
      ends were tied ligating the spermatic cord, leaving the knot subcutaneously.
      Calves were monitored and testes removed after 30 days for gross and histologic
      examination. RESULTS: Castration was accomplished without postoperative
      complications. Spermatic cord ligation resulted in testis atrophy, and
      histologically, complete ischemic necrosis. CONCLUSIONS: This novel minimally
      invasive technique is a simple, alternative method for castration of bull calves.
      CLINICAL RELEVANCE: This method of castration is simply performed, without
      obvious skin wounds, and no postoperative care needed. The technique should be
      readily adaptable to other species.

PMID- 17214825
TI  - In vitro biomechanical properties of linear, circular, and hybrid external
      skeletal fixation devices for use in large ruminants.
AB  - OBJECTIVE: To report the biomechanical properties of 3 external skeletal fixation
      (ESF) devices for use in large ruminants. STUDY DESIGN: In vitro biomechanical
      testing of ESF constructs. SAMPLE POPULATION: Adult buffalo (weighing, 250-350
      kg) tibiae (n=27). METHODS: ESF constructs (bilateral linear fixator [BLF], 4
      ring circular external fixator [CEF], and hybrid fixator [HF]) were made using
      mild (low carbon) steel implants plated with nickel and cadaveric buffalo tibiae.
      After ESF application, a 1 cm mid-diaphyseal gap was created. Constructs were
      loaded to failure, on a materials testing machine, in axial compression (n=5/ESF
      type) and craniocaudal bending (n=3/ESF type). In addition, 3 CEF constructs were
      tested in intact tibiae under craniocaudal bending. RESULT: In compression, HF
      was the strongest and most rigid construct; yield load was significantly higher
      for HF than for BLF or CEF. Under bending, both CEF and HF had similar strength
      and modulus of elasticity. Strength for BLF was higher than CEF and HF, whereas
      the reverse was true for modulus of elasticity. CONCLUSIONS: ESF made from mild
      steel for use in large ruminants could withstand<or=300 kg load applied under
      compression and bending moment without any substantial adverse biomechanical
      effects on the constructs. HF was most rigid and strong under compression,
      whereas BLF was strongest in craniocaudal bending. Overall, HF seemed
      biomechanically the most suitable ESF device. CLINICAL RELEVANCE: A hybrid ESF
      developed using mild steel is sufficiently strong and economical and may prove
      useful for fixation of long bone fractures in large ruminants (weighing<or=300
      kg).

PMID- 17214826
TI  - Evaluation of two dynamic axial fixators for large ruminants.
AB  - OBJECTIVES: To evaluate healing of a radial osteotomy repaired by application of
      dynamic axial fixation devices (DAF) in large ruminants. STUDY DESIGN: In vivo
      study of bone healing after application of 2 DAF types. Model I had 2 sidebars,
      each with a central cylindrical cuff (internally threaded) with 2 detachable
      connecting rods telescoping within the cuff. Model II had 2 side bars with 2
      moveable clamps with multiple holes. SAMPLE POPULATION: Bull calves (n=8; aged,
      1.5-2.0 years; weighing, 175-250 kg). METHODS: A mid-diaphyseal radial osteotomy
      was repaired by use of a model I (n=4) or model II (n=4) DAF. Calves were
      monitored for weight bearing, stability of fixation, and radiographically for
      fracture reduction, alignment and healing at intervals for 6 months. Fixators
      were removed when there was radiographic evidence of healing. RESULTS: Both the
      fixators were well tolerated with free movement of adjacent joints. Fragment
      fixation was maintained until healing in all but 1 model I calf where failure
      occurred within 7 days. Model II DAF provided more rigid fixation as indicated by
      early full weight bearing and fracture healing with less callus formation.
      Functional recovery of repaired limbs occurred within 60 days in surviving
      calves. CONCLUSIONS: Both bilateral DAFs were easy to apply; however, the model
      II DAF provided better fixation. CLINICAL RELEVANCE: The model II DAF made of low
      carbon steel was economical and may be useful for treating long bone fractures in
      large ruminants.

PMID- 17214827
TI  - Time-dependent clearance of mycophenolic acid in renal transplant recipients.
AB  - AIMS: Pharmacokinetic studies of the immunosuppressive compound mycophenolic acid
      (MPA) have shown a structural decrease in clearance (CL) over time after renal
      transplantation. The aim of this study was to characterize the time-dependent CL
      of MPA by means of a population pharmacokinetic meta-analysis, and to test
      whether it can be described by covariate effects. METHODS: One thousand eight
      hundred and ninety-four MPA concentration-time profiles from 468 renal transplant
      patients (range 1-9 profiles per patient) were analyzed retrospectively by
      nonlinear mixed effect modelling. Sampling occasions ranged from day 1-10 years
      after transplantation. RESULTS: The pharmacokinetics of MPA were described by a
      two-compartment model with time-lagged first order absorption, and a first-order
      term for time-dependent CL. The model predicted the mean CL to decrease from 35 l
      h(-1) (CV = 44%) in the first week after transplantation to 17 l h(-1) (CV = 38%)
      after 6 months. In a covariate model without a term for time-dependent CL,
      changes during the first 6 months after transplantation in creatinine clearance
      from 19 to 71 ml min(-1), in albumin concentration from 35 to 40 g l(-1), in
      haemoglobin from 9.7 to 12 g dl(-1) and in cyclosporin predose concentration from
      225 to 100 ng ml(-1) corresponded with a decrease of CL from 32 to 19 l h(-1).
      Creatinine clearance, albumin concentration, haemoglobin and cyclosporin predose
      concentration explained, respectively, 19%, 12%, 4% and 3% of the within-patient
      variability in MPA CL. CONCLUSIONS: By monitoring creatinine clearance, albumin
      concentration, haemoglobin and cyclosporin predose concentration, changes in MPA
      exposure over time can be predicted. Such information can be used to optimize
      therapy with mycophenolate mofetil.

PMID- 17214828
TI  - Isotretinoin, pregnancies, abortions and birth defects: a population-based
      perspective.
AB  - AIMS: To estimate the population-based incidence rates of pregnancy, spontaneous
      and elective abortions, and birth defects associated with isotretinoin use, and
      to determine predictors of pregnancy while on isotretinoin. METHODS: Using the
      RAMQ (medical and pharmaceutical data), MED-ECHO (hospitalizations) and ISQ
      (births and deaths) databases for the period 1984-2002, a cohort of 8609 women
      between 13 and 45 years of age and with a first prescription for isotretinoin
      (date of entry in the cohort) was identified. Women were eligible if they were
      insured by RAMQ for their medications at least 12 months before entry in the
      cohort and until 1 month after the end of their isotretinoin treatment.
      Pregnancies, spontaneous and elective abortions, and birth defects were
      identified using procedure codes and medical diagnoses. RESULTS: Of the 8609
      women included, 90 became pregnant, an annual incident pregnancy rate during
      isotretinoin treatment of 32.7 per 1000 person-years of treatment (95% confidence
      interval 26.6, 40.1). Of the 90 women who became pregnant while on the drug, 76
      terminated the pregnancy (84%), three had a spontaneous abortion (3%), two had
      trauma during delivery resulting in neonatal deaths (2%) and nine had a live
      birth (10%). Among the live births, only one had a congenital anomaly of the face
      and neck (11%). Adjusting for potential confounders, predictors of becoming
      pregnant while on isotretinoin were lower socio-economic level, one or more
      visits to the doctor or to the emergency department, or one or more
      hospitalization while on isotretinoin; concomitant isotretinoin and oral
      contraceptive use had a preventive effect. CONCLUSIONS: This first non
      interventional population-based study generated incidence rates of pregnancy
      while on isotretinoin four times greater than what has been reported in the
      literature thus far; elective abortion rates were also much higher in our study.
      This shows the importance of using population-based data for public health
      purposes.

PMID- 17214830
TI  - Disease mongering -- a challenge for everyone involved in healthcare.

PMID- 17214829
TI  - Impact of atorvastatin treatment on platelet-activating factor acetylhydrolase
      and 15-F(2trans)-isoprostane in hypercholesterolaemic patients.
AB  - AIMS: Isoprostanes are the product of free radical oxidation of arachidonic acid,
      whose hydrolysis from phospholipids is presumably catalysed by phospholipases
      A(2) (PLA(2)s) such as group IIA or V PLA(2)s, or group VII PLA(2)[platelet
      activating factor acetylhydrolase (PAF-AH), lipoprotein-associated
      phospholipase]. Atorvastatin reduces concentrations of low-density lipoprotein
      (LDL), with which PAF-AH is associated, and PLA(2)s' protein concentrations. We
      investigated the effect of atorvastatin on PLA(2)s and PAF-AH activity and the
      urinary excretion of 15-F(2trans)-isoprostane (15-F(2t)-IsoP, 8-iso-PGF(2alpha),
      iPF(2alpha)-III). METHODS: Twenty-four hypercholesterolaemic individuals naive to
      lipid-lowering therapy were randomized to atorvastatin 40 mg or placebo for 6
      weeks. The 15-F(2t)-isoP urinary excretion (gas chromatography/mass
      spectrometry), PAF-AH and group IIA and V PLA(2) activities (photometry) were
      assessed at baseline and end-point. RESULTS: At end-point, 15-F(2t)-isoP urinary
      excretion concentrations as well as PLA(2)s' activity were unchanged under
      atorvastatin (mean change 0.21 +/- 1.79 ng h(-1), 95% confidence interval -0.92,
      1.35 and 0.33 +/- 0.94 nmol min(-1) ml(-1), -0.27, 0.93) and under placebo (mean
      change 0.69 +/- 1.69 ng h(-1), -0.52, 1.90 and 1.29 +/- 2.16 nmol min(-1) ml(-1),
      -0.25, 2.84). Atorvastatin treatment decreased total (P < 0.001) and LDL
      cholesterol (P < 0.001) but had no effect on high-density lipoprotein. PAF-AH
      activity was lowered in the atorvastatin group (mean change - 5.27+/- 1.96 nmol
      min(-1) ml(-1), -6.51, -4.03, P < 0.001) but not in the placebo group (mean
      change 1.02 +/- 1.64 nmol min(-1) ml(-1), 0.15, 2.20), and the change in PAF-AH
      activity was correlated with that in total (P = 0.03) and LDL-cholesterol (P =
      0.03). CONCLUSION: Our results show a lowering effect of atorvastatin on PAF-AH
      activity associated with its lipid-lowering effect and exclude a key role of PAF
      AH in the liberation of 15-F(2t)-isoP from phospholipids.

PMID- 17214832
TI  - Host responses in periodontal diseases: a preview.

PMID- 17214831
TI  - Impact of adherence to statins on coronary artery disease in primary prevention.
AB  - AIMS: To evaluate the impact of adherence to statins on nonfatal coronary artery
      disease (CAD). Statins reduce cardiovascular morbidity and mortality after 1-2
      years of continuous treatment. Studies have shown that <40% of patients take > or
      =80% of prescribed doses 1 year after starting therapy and that approximately
      half discontinue medication within 6 months of starting therapy. METHODS: A
      cohort of 20 543 patients was reconstructed using the Regie de l'assurance
      maladie du Quebec databases. Patients aged 50-64 years, without cardiovascular
      disease, and newly treated with statins between 1998 and 2000 were eligible. A
      nested case-control design was used to study nonfatal CAD. Every case was matched
      with 20 randomly selected controls. The adherence level was defined as the
      percentage of the prescribed medication doses used over a specified period and
      classified as > or =90% or <90%. Rate ratios (RR) of nonfatal CAD were determined
      through conditional logistic regression adjusted for age, sex, socioeconomic
      status, diabetes and hypertension. RESULTS: The mean patient age was 58 years,
      45% had hypertension and 19% had diabetes. Men represented 37% of the cohort.
      Among patients followed for >1 year, adherence of > or =90% was associated with
      fewer nonfatal CAD events (RR 0.81; 0.67, 0.97) compared with adherence <90%. In
      the multivariate model, male gender (RR 1.37; 1.16, 1.63), welfare recipients (RR
      1.24; 1.04, 1.48), newly diagnosed hypertension (RR 3.54; 2.62, 4.77) and newly
      diagnosed diabetes mellitus (RR 1.97; 1.20, 3.24) were risk factors for CAD.
      CONCLUSION: The incidence of nonfatal CAD events decreases when >90% of the
      prescribed medications is used over at least 1 year.

PMID- 17214833
TI  - The role of T cells in periodontal disease: homeostasis and autoimmunity.

PMID- 17214834
TI  - Toll-like receptors and their role in periodontal health and disease.

PMID- 17214835
TI  - Signal transduction of lipopolysaccharide-induced osteoclast differentiation.

PMID- 17214836
TI  - Roles of receptor activator of nuclear factor-kappaB ligand (RANKL) and
      osteoprotegerin in periodontal health and disease.

PMID- 17214837
TI  - The roles of cyclooxygenase-2 and prostaglandin E2 in periodontal disease.

PMID- 17214838
TI  - The role of genetic polymorphisms in periodontitis.

PMID- 17214839
TI  - Determinants of host susceptibility in aggressive periodontitis.

PMID- 17214840
TI  - The role of reactive oxygen and antioxidant species in periodontal tissue
      destruction.

PMID- 17214842
TI  - The periodontal host response with diabetes.

PMID- 17214843
TI  - Metabolic disorders related to obesity and periodontal disease.

PMID- 17214841
TI  - Diabetic periodontitis: a model for activated innate immunity and impaired
      resolution of inflammation.

PMID- 17214844
TI  - The influence of smoking on host responses in periodontal infections.

PMID- 17214845
TI  - Clinical relevance of the host responses of periodontitis.

PMID- 17214847
TI  - Cancer/testis antigen MAGE-A4 expression pattern differs in epithelial skin
      tumors of organ-transplant recipients and immunocompetent patients.
AB  - BACKGROUND: Lifetime risk for squamous cell carcinoma (SCC) of the skin is 1:30.
      Risk in organ-transplant recipients (OTR) is increased over 60-fold through long
      term drug-induced immunosuppression. MAGE family-derived peptides are
      cancer/testis antigens recognized by specific CD8(+) T cells and employed for
      immunotherapy. We were interested in the frequency and distribution of MAGE-A4 in
      epithelial skin tumors of OTR and immunocompetent patients. METHODS: mAb 57B
      predominantly recognizing MAGE-A4 was used to stain 119 formalin-fixed, paraffin
      embedded epithelial skin tumors (actinic keratosis, bowenoid actinic keratosis,
      Bowen's disease, and SCC; n = 17, 25, 61, 16, respectively) in immunocompetent
      patients (n = 84) and OTR (n = 35). RESULTS: All four epithelial skin tumors
      showed comparable immunoreactivity ranging from (25-71%, p = 0.361). Scattered
      immunoexpression pattern was more frequent in OTR (p = 0.025). SCC showed
      polarized immunoreactivity basally (p = 0.002). CONCLUSION: MAGE-A4 was expressed
      in a large part of epithelial skin tumors with predominantly scattered
      immunoexpression pattern in OTR. The difference in immunoexpression pattern for
      immune status was limited, suggesting important non-immunosuppressor-mediated
      mechanisms for increased skin carcinogenesis in OTR. mAb 57B may be a helpful
      tool for immunohistochemistry and micrographic surgery using formalin-fixed
      paraffin-embedded tissue.

PMID- 17214848
TI  - Protein expression of melanocyte growth factors (bFGF, SCF) and their receptors
      (FGFR-1, c-kit) in nevi and melanoma.
AB  - BACKGROUND: Basic fibroblast growth factor (bFGF) and stem cell factor (SCF) are
      essential growth factors for melanocytes which carry the receptors FGFR-1 for
      bFGF and c-kit for SCF. Because both factors may be involved in melanoma
      development, the expression of bFGF/FGFR-1 and SCF/c-kit was investigated in
      melanocytic tumors of different progression stages. METHODS: Fifty primary
      melanomas and 44 melanocytic nevi were analyzed for the expression of SCF, c-kit,
      bFGF, and FGFR-1 by immunohistochemistry. RESULTS: In melanoma, SCF and c-kit
      were expressed in 76 and 84%, respectively, and coexpressed in 66%. bFGF and FGFR
      1 were expressed in 45 and 86%, respectively, and coexpressed in 46%. In
      melanocytic nevi, SCF was expressed in 23% and c-kit in 70% while coexpression
      was more common in dysplastic (39%) than non-dysplastic subtypes (8%). bFGF and
      FGFR-1 were expressed in 55 and 67%, respectively, while coexpression was found
      in 47% but varied considerably between different histological subtypes.
      CONCLUSIONS: SCF and c-kit were frequently expressed by melanomas and dysplastic
      nevi suggesting an autocrine growth mechanism as described for bFGF. In both nevi
      and melanoma, c-kit was almost exclusively found in the epidermis while bFGF was
      more common in the dermis. Thus the growth factor/receptor expression seems to
      depend on the cutaneous localization of the melanocytic tumors.

PMID- 17214849
TI  - Clinical and immunohistochemical assessment of the effect of cyclosporin in
      keratinocytes and dermal dendrocytes in psoriasis.
AB  - BACKGROUND: Cyclosporine is a potent immunosupressor, which induces cytokeratin
      expression pattern changes and dermal dendrocytes number increase. OBJECTIVES: To
      evaluate its clinical effect in psoriasis, on keratinocytic proliferation and
      differentiation, and on dermal dendrocytes proliferation. METHODS: Thirty
      patients with psoriasis were treated and evaluated for 8 weeks. Clinical
      improvement was evaluated by Psoriasis Area and Severity Index (PASI). Biopsies
      were performed initially and after 8 weeks. Immunohistochemistry [CK markers 10,
      14, and 16, and factor XIIIa+ (FXIIIa+)] was performed. RESULTS: Mean PASI before
      treatment was 26.32 and 3.71 after. Mean initial and final PASI difference was
      22.61 (p < 0.001). Two patients had serum creatinine and six uric acid increase.
      Before and after treatment, mean numbers per field of dermal dendrocytes were
      7.07 and 3.68, respectively. Mean difference was 3.39, with p < 0.001. CK10
      immunohistochemical pattern demonstrated recovery of normal expression pattern in
      26 patients, while CK14 pattern demonstrated improvement in 21 patients.
      CONCLUSIONS: Cyclosporine was effective and safe for psoriasis in low doses, with
      significant decrease of PASI and dermal dendrocytes number after 8 weeks of
      therapy. CK10 and 14 pattern changed and, less prominently, CK16 expression.
      These modifications occur later than the PASI and dermal dendrocytes variation.

PMID- 17214846
TI  - Novel host response therapeutic approaches to treat periodontal diseases.

PMID- 17214850
TI  - The Wnt-signaling pathway is not implicated in tumorigenesis of Merkel cell
      carcinoma.
AB  - BACKGROUND: The Wnt-signaling pathway, involving beta-catenin, apc, and axin,
      plays a critical role in numerous developmental events. Alterations in the Wnt
      signaling pathway have been detected in a wide variety of neoplasms. However,
      similar aberrations have not been described in Merkel cell carcinoma (MCC). The
      aim of this study was to determine the status of the Wnt-signaling pathway in
      MCC. METHODS: Twelve cases of MCC were tested for the expression of beta-catenin
      and mutational status of CTNNB1 (gene for beta-catenin), APC, AXIN1, and AXIN2.
      Genomic DNA extracted from paraffin blocks was subjected to a polymerase chain
      reaction/single-strand conformation polymorphism analysis and sequencing.
      RESULTS: Nuclear accumulation of beta-catenin was observed in only one case
      (8.3%), as determined by immunochemistry. No mutations were found in CTNNB1, APC,
      and AXIN2 in all cases, although silent mutations in AXIN1 were detected in three
      cases. CONCLUSIONS: We conclude that the Wnt-signaling pathway does not play an
      important role in tumorigenesis in MCC.

PMID- 17214851
TI  - Analysis of the CC chemokine receptor 5 delta32 polymorphism in a Brazilian
      population with cutaneous leishmaniasis.
AB  - Patients with mucocutaneous leishmaniasis (MCL) show a vigorous T-cell immune
      response against Leishmania braziliensis. Because the Th response is associated
      with inflammation, the non-functional CC chemokine receptor 5 (CCR5) may rely in
      a less severe inflammatory state. The aim of this study was to investigate the
      CCR5 gene in a Brazilian population with leishmaniasis compared with healthy
      control subjects and to determine the progression from cutaneous to MCL in the
      Delta32 allele carriers. Among 100 patients with Montenegro skin test and
      indirect immunofluorescence assay (IIF) values positive for leishmaniasis, there
      were 32% women and 68% men. The patients were 89% CCR5/CCR5, 10% CCR5/Delta32,
      and 1% Delta32/Delta32, while healthy subjects showed a 91% incidence of
      CCR5/CCR5, 8% of CCR5/Delta32, and 1% of Delta32/Delta32. The CCR5/CCR5 patients
      (89%) showed a large spectrum of clinical manifestations, where 22.47% had active
      mucous lesions and 77.53% had cutaneous lesions. In this work, the Delta32 allele
      carriers (10%) showed only cutaneous manifestations when compared with wild-type
      individuals. Finally, with regard to the Delta32 allele carriers, a less severe
      spectrum of clinical manifestations was observed in comparison with wild-type
      individuals. Although a lack of mucocutaneous lesions was evident among Delta32
      allele carriers, the number of individuals studied was small. Therefore, further
      investigations are needed to elucidate the role of CCR5 in the clinical aspects
      of leishmaniasis.

PMID- 17214852
TI  - Expression and prognostic significance of Stat5a and E-cadherin in extramammary
      Paget's disease.
AB  - BACKGROUND: Stat5 has been shown to regulate the proliferation and inhibition of
      apoptosis in cancer cells. E-cadherin plays an important role in maintaining
      epithelial stability and is widely regarded as a prognostic marker in many types
      of human cancers. The expression of Stat5 has not been investigated in
      extramammary Paget's disease (EMPD). OBJECTIVES: To study the expression of
      Stat5a and E-cadherin protein in EMPD and to evaluate the relationships between
      them. METHODS: Thirty-six tissue samples from 34 cases with primary EMPD were
      subjected to immunohistochemical staining for Stat5a and E-cadherin. RESULTS:
      Twenty-nine of 30 in situ EMPD specimens were positive for Stat5a expression, and
      the staining pattern for Stat5a was mainly nuclear in the majority of Paget's
      cells. All four invasive specimens and two metastatic lymph node specimens were
      negative for Stat5a. Twenty-six of 30 in situ EMPD specimens expressed E-cadherin
      in more than 50% of tumor cells, and three of 30 in situ EMPD specimens expressed
      E-cadherin in less than 50% of tumor cells. One in situ EMPD specimen and one
      invasive specimen expressed E-cadherin in less than 25% of tumor cells. Three
      invasive specimens and two metastatic lymph node specimens were negative, with
      occasional membranous staining for E-cadherin. There is a significant correlation
      between the expression of Stat5a and E-cadherin. CONCLUSIONS: Our results showed
      that these proteins were found in in situ lesions, and it is speculated that
      these proteins may play some role in the prognosis/invasion of EMPD.

PMID- 17214853
TI  - Cutaneous changes in fibrous hamartoma of infancy.
AB  - BACKGROUND: Fibrous hamartoma of infancy (FHI) is a fast growing soft tissue
      tumor that usually arises in the first 2 years of life. The histology of the
      lesion has been well described. Few studies, however, have looked at changes in
      the overlying skin and its appendages. METHODS: A database search performed at
      British Columbia Children's Hospital yielded 15 cases of unequivocal FHI
      occurring in 12 patients (three were recurrences). Of these, we were able to
      retrieve 13. Five of 13 cases had sections including epidermis. These slides were
      reviewed with specific emphasis on skin adnexae. RESULTS: Of the cases with
      excised epidermis in continuity with the lesion, 5/5 had eccrine changes,
      including hyperplasia, duct dilatation, intraluminal papillary formations, and
      squamous syringometaplasia. One case showed epidermal basaloid follicular
      hyperplasia. CONCLUSIONS: This study shows that eccrine changes are frequently
      seen in cases of FHI when overlying skin is sampled. This may be a useful clue to
      consider this diagnosis, especially when the biopsy is superficial.

PMID- 17214854
TI  - Changes of epidermodysplasia verruciformis in benign skin lesions: the EV
      acanthoma.
AB  - Foci of histological changes of epidermodysplasia verruciformis (EV) were noted
      in five benign skin lesions. These skin lesions included an intradermal nevus, a
      pigmented seborrheic keratosis, an isolated papule on the forearm, a perianal
      lesion, and an acantholytic acanthoma. Because the changes resembled true EV so
      strongly despite the absence of clinical EV in these patients, we searched for EV
      human papilloma virus (HPV) types in these skin lesions. Polymerase chain
      reaction (PCR) analysis on the formalin-fixed, paraffin-embedded blocks was
      performed. As a positive control, we included tissue from two HIV-positive
      patients with clinical EV proven by biopsy. Studies were also performed on five
      other archived biopsies that did not show changes of EV on multiple tissue
      sections. A nested PCR method detected EV-HPV types in three of the five benign
      skin lesions showing EV changes as well as in the positive controls. EV changes
      and EV-HPV can be found incidentally on biopsy in the absence of clinical EV;
      when such changes are the major histopathological finding in an isolated skin
      lesion, the lesion should be termed an EV acanthoma.

PMID- 17214855
TI  - Metastatic hidradenocarcinoma with demonstration of Her-2/neu gene amplification
      by fluorescence in situ hybridization: potential treatment implications.
AB  - A 44-year-old man was referred for a right chest nodule of 3 months duration. A
      'benign' nodule had been excised from this location 8 years prior. On
      examination, palpable nodes were noted in the right axilla. Radiographic studies
      were significant only for right axillary lymphadenopathy. Histologically, a
      nodular dermal proliferation composed of poorly differentiated epithelioid cells
      in nests and focally forming ducts with pseudopapillary architecture comprised
      the primary tumor. Features of a clear cell hidradenoma were noted focally.
      Immunohistochemical (IHC) analysis revealed reactivity for HMW cytokeratins, CK5
      and CK7, p53, p63, CEA (focal), androgen receptor, EGFR, estrogen receptor (ER),
      MUC5AC, and strong/diffuse membranous staining for Her-2/neu. Negative stains
      included villin, TTF-1, CDX2, S-100 protein, vimentin, gross cystic disease fluid
      protein 15 (GCDFP-15), mammoglobulin, and MUC2. A wide local excision and
      axillary node dissection was performed. Metastatic tumor involved nine of 28
      nodes. Interphase fluorescence in situ hybridization (FISH) demonstrated
      chromosomal amplification of the Her-2/neu locus within the tumor and a nodal
      metastasis. The patient has completed adjuvant and radiotherapy, including
      trastuzumab, and is asymptomatic. We believe this to be the first demonstration
      of Her-2/neu amplification in a malignant skin adnexal tumor. In analogy to
      breast carcinoma, these findings suggest the applicability of trastuzumab for
      patients with metastatic adnexal carcinomas demonstrating Her-2/neu
      amplification.

PMID- 17214856
TI  - Sarcomatoid eccrine porocarcinoma: report of two cases and a review of the
      literature.
AB  - Eccrine porocarcinoma is an uncommon sweat gland malignancy. To the best of our
      knowledge, there has been no report in the English literature of porocarcinoma
      with predominantly undifferentiated sarcomatous change. We present two cases of
      sarcomatoid eccrine porocarcinoma associated with a benign poroma. Case 1
      pertained to an 82-year-old woman with an ulcerated chest wall tumor, and Case 2
      was that of a 74-year-old woman who presented with an ulcerated plaque in the
      lower leg. Case 1 showed an unusual pseudo-angiosarcomatous morphology with
      spindle cells dissecting through collagen bundles and forming vascular like
      channels. Case 2 revealed high-grade malignant spindle cells with focal evidence
      of ductal differentiation. In both the cases, benign poromatous elements were
      histologically evident. Immunohistochemistry performed showed pancytokeratin
      positivity in spindle cells of both lesions. Epithelial membrane antigen and
      carcino-embryonic antigen positivity in the malignant ductal elements and focal
      smooth muscle actin staining of the spindle cells were demonstrated in Case 2. A
      brief review of relevant literature is presented.

PMID- 17214857
TI  - Primary cutaneous osteosarcoma of the scalp: a case report and review of the
      literature.
AB  - We report on an 84-year-old man with a solitary, nodular lesion on the scalp. The
      patient had been previously submitted to electrodessications of the scalp due to
      multiple solar keratoses. Histopathologically, the lesion showed features of a
      high-grade conventional osteoblastic osteosarcoma involving the dermis. Computed
      tomography showed no involvement of the underlying bone tissues. Clinical
      examination and extensive total body radiologic workup revealed absence of bone
      lesions in any body site, thus suggesting a final diagnosis of primary cutaneous
      extraskeletal osteosarcoma. The clinico-pathological features of the case are
      discussed in light of the rare cases previously described in the literature.

PMID- 17214858
TI  - Congenital linear unilateral basal cell nevus: a case report with patched gene
      molecular studies.
AB  - BACKGROUND: Linear unilateral basal cell nevus represents a linear collection of
      macules and papules histologically similar to basal cell carcinoma but with
      benign clinical behavior. We describe a patient who initially presented at the
      age of 6 months with a unilateral linear basal cell nevus on the right flank. The
      differential diagnosis included the nevoid basal cell carcinoma syndrome.
      Constitutional PTCH mutations are causative of the nevoid basal cell carcinoma
      syndrome, and somatic PTCH mutations are found in the vast majority of basal cell
      carcinomas. Somatic SMO mutations have also been found in some basal cell
      carcinomas. METHODS: Histologic examination of the lesions is performed. Short
      tandem-repeat molecular analysis at the PTCH locus and sequencing of PTCH and SMO
      genes is performed. RESULTS: Histologic examination revealed features initially
      indistinguishable from basal cell carcinoma. Short tandem-repeat DNA analysis did
      not reveal loss of heterozygosity at the PTCH locus. DNA sequencing of both the
      PTCH and the SMO genes from the patient's lesions revealed neither inactivating
      mutations of PTCH nor activating mutations of SMO. CONCLUSION: Molecular
      examination indicates that the PTCH and SMO genes are not involved in the
      pathogenesis of the patients' congenital linear unilateral basal cell nevus.
      Furthermore, we discuss the relationship between linear basal cell nevus and
      basaloid follicular hamartoma.

PMID- 17214859
TI  - Zeil Neelson and Wade-Fite stains to demonstrate medlar bodies of
      chromoblastomycosis.

PMID- 17214860
TI  - Public access defibrillation programs: Role for nurse practitioners.

PMID- 17214861
TI  - Nursing center annual reports: Value and content.

PMID- 17214862
TI  - The transtheoretical model and primary care: "The Times They Are A Changin'".
AB  - PURPOSE: To identify the transtheoretical model and the five stages of change
      that assist to bring about behavioral change. A case study is presented to
      illustrate how the model can be applied by primary care nurse practitioners (NPs)
      to assist patients toward a healthier lifestyle. DATA SOURCES: Scientific
      literature, theoretical framework, and case study. CONCLUSIONS: The
      transtheoretical model has implications in primary care to assist NPs in
      assessing what stage a patient may be in, offering encouragement to promote a
      healthier lifestyle change, and reassessing the patient to maintain the desired
      healthy behavior. IMPLICATIONS FOR PRACTICE: Primary care NPs can use the
      transtheoretical model to better advance patients into a healthy behavioral
      change. Documentation of the current stage a patient is in can promote continuity
      of care among providers, outline specific health promotion initiatives to enhance
      patient care, and provide documentation during regulatory inspections.

PMID- 17214863
TI  - Barriers to immunizations: Multiethnic parents of under- and unimmunized children
      speak.
AB  - PURPOSE: Childhood immunizations are one of the greatest pubic health success
      stories. Despite the fact that many children receive immunizations according to
      the recommended schedule, there are many that lag behind. The purpose of this
      study was to explore the barriers to immunizations in parents whose children are
      not fully immunized by age 2. DATA SOURCE: Thirteen focus groups, on four
      different islands (Oahu, Kauai, Maui, Hawaii) were held with a total of 64
      parents. Verbatim transcripts were utilized for content analysis. CONCLUSION:
      Five core themes emerged as barriers to childhood immunizations, parental,
      transportation, financial, child, and organization. The majority of responses
      were in the parental core theme, which included the sub-themes of issues,
      beliefs, knowledge, and fears. IMPLICATIONS FOR PRACTICE: Recommendations
      included identification of specific barriers to target immunization interventions
      strategies, public policy changes, identification and case management of high
      risk families, and minimization of organizational barriers.

PMID- 17214864
TI  - Preceptor rewards: How to say thank you for mentoring the next generation of
      nurse practitioners.
AB  - PURPOSE: To answer the question how do faculty nurture and reward clinical
      preceptors and what supports do preceptors require? DATA SOURCES: Data came from
      the literature and from surveying a purposive sample of 26 faculty members
      teaching clinical courses and arranging precepted experiences for nurse
      practitioner (NP) students at 26 public and private institutions across the
      United States. The vehicles for the survey were personal contact and e-mail.
      CONCLUSIONS: Schools offer preceptor rewards varying widely in their monetary
      value, from tuition and continuing education vouchers, verification of hours
      toward recertification, access to services and events on campus, reduced price or
      free admission to museums, cultural and sports events, and lectures. Faculty
      nurture preceptors by nominating them for awards, providing letters of reference,
      editing manuscripts, and collaborating on research projects. Supports for
      preceptors from the literature reflected National Organization of Nurse
      Practitioner Faculties guidelines (2000), and the policies of schools and
      clinical agencies, such as providing copies of program objectives and student
      credentials. IMPLICATIONS FOR PRACTICE AND EDUCATION: As NP programs have
      proliferated, there is increased pressure on faculty to find, nurture, reward,
      and retain good preceptors. Faculty must continue to work with program and agency
      administrators to comply with policies and create preceptor rewards to recognize
      their gifts to us, to our schools, and to the profession.

PMID- 17214865
TI  - Job satisfaction among Arizona adult nurse practitioners.
AB  - PURPOSE: A literature review for studies of job satisfaction among nurse
      practitioners (NPs) suggests that the true determinants of job satisfaction have
      not been discovered. The purpose of this study was to determine job satisfaction
      among adult health NPs (ANPs) practicing in Arizona. DATA SOURCES: The Misener
      nurse practitioner job satisfaction scale was mailed to 329 Arizona ANPs who were
      certified by the Arizona State Board of Nursing (47% response rate). CONCLUSIONS:
      The mean overall satisfaction score was 4.69 out of a possible score of 6.0 for
      very satisfied. Differences in employer type, gender, annual income, membership
      in professional nursing organization, or full-time versus part-time employment
      status did not result in significantly different scores on the job satisfaction
      scale in this group. IMPLICATIONS FOR PRACTICE: A deep and sustained nursing
      shortage, the exodus of experienced nurses from the profession, and a projected
      shortage of primary care providers have generated interest among professional
      groups, private and government healthcare commissions, and the healthcare
      industry in determining what factors may influence an individual to choose and
      remain active in nursing practice. Researchers, educators, employers, and the
      healthcare industry must look beyond well-worn assumptions about job satisfaction
      to explore what the individual NP finds satisfying about his or her role.

PMID- 17214866
TI  - How well are nurse practitioners prepared for practice: Results of a 2004
      questionnaire study.
AB  - PURPOSE: The purpose of this study was to evaluate the perceived preparedness of
      nurse practitioners (NPs) for practice after completing their basic NP
      educational programs and to evaluate NPs' perceived preparedness in and their
      perceived importance of select clinical content areas basic to NP education. DATA
      SOURCES: This cross-sectional descriptive study used a written questionnaire
      consisting of 32 items, two of which contained 25 subitems. Subjects were asked
      to rate their overall level of preparedness when they completed their NP program
      and both their level of preparation in and the importance of 25 clinical content
      areas. The questionnaires were administered to attendees at two large national NP
      conferences in 2004; a total of 562 questionnaires were completed and used in the
      analysis. CONCLUSIONS: Ten percent of the sample perceived that they were very
      well prepared for practice as an NP after completing their basic NP education.
      Fifty-one percent perceived that they were only somewhat or minimally prepared.
      Current age, years since graduation from an NP program, and age when attending
      the NP program did not differ significantly for those who felt prepared versus
      those who did not. For a number of content areas, subjects did not perceive that
      they were well prepared in the same areas that they perceived were very
      important. IMPLICATIONS FOR PRACTICE: Our results indicate that formal NP
      education is not preparing new NPs to feel ready for practice and suggests
      several areas where NP educational programs need to be strengthened. Practicing
      NPs are the basis of the NP profession, and their views need to be sought,
      listened to, and reflected upon as we advance toward expanded preparation at the
      doctoral level.

PMID- 17214867
TI  - A case study of an older adult with severe anemia refusing blood transfusion.
AB  - PURPOSE: To discuss the diagnosis and treatment of severe anemia in an older
      adult who presents the challenge of declining blood transfusion in a real-world
      scenario where critical thinking, evidence-based care, and collaboration with
      other providers must come together to serve this patient's unique needs. DATA
      SOURCES: Extensive review of the scientific literature on anemia and the
      situation in which a patient refuses blood transfusion presented in a case study
      format. CONCLUSIONS: A thorough physical assessment, complete health history, and
      appropriate diagnostic workup should be used to distinguish the normal effects of
      senescence from the signs and symptoms of anemia. Common conditions that cause
      anemia in the elderly include chronic disease, iron deficiency, and
      gastrointestinal bleeding. These conditions may result in profound anemia. The
      challenge can be compounded when, because of religious tenets, a patient does not
      accept a blood transfusion. This case study challenges nurse practitioners to
      apply knowledge, seek guidance, and make appropriate referrals to care for a
      patient in order to render care within the parameters of the patient's belief
      system. IMPLICATIONS FOR PRACTICE: The astute primary care provider recognizes
      that anemia is not an expected physiological change associated with aging but a
      manifestation of an underlying disease process. Fatigue, weakness, and dyspnea
      are all symptoms of anemia that may be overlooked and attributed to the aging
      process. Further, in keeping with the principles of autonomy and self
      determination, it is the clinician's duty to work with all patients to restore
      them to a state of optimal health while respecting deeply held spiritual beliefs.

PMID- 17214868
TI  - Nurse Practitioner Corporate Partner Council.

PMID- 17214869
TI  - The critical period hypothesis: can it explain discrepancies in the oestrogen
      cognition literature?
AB  - Although there is compelling evidence from small randomised controlled trials and
      cross-sectional studies indicating that oestrogen helps to protect against
      cognitive ageing in women, the findings of the large, Women's Health Initiative
      Memory Study failed to support the earlier findings. The attempt to resolve these
      discrepancies led to the formulation of the Critical Period Hypothesis which
      holds that oestrogen has maximal protective benefits on cognition in women when
      it is initiated closely in time to a natural or surgical menopause but not when
      treatment is begun decades after the menopause. This article reviews the evidence
      from basic neuroendocrinology, from animal behavioural studies and from human
      studies that supports the critical period hypothesis. In view of the promise of
      this hypothesis and its considerable clinical implications, a direct test of its
      validity is warranted.

PMID- 17214870
TI  - Altered expression of SOCS3 in the hypothalamic arcuate nucleus during seasonal
      body mass changes in the field vole, Microtus agrestis.
AB  - We have previously shown that cold-acclimated (8 degrees C) male field voles
      (Microtus agrestis) transferred from short day (SD, 8 h light) to long day (LD,
      16 h light) photoperiod exhibit an increase in body mass lasting 4 weeks, after
      which they stabilise at a new plateau approximately 7.5 g (24.8%) higher than
      animals maintained in SD. By infusing voles with exogenous leptin, we have also
      demonstrated that SD voles respond to the hormone by reducing body mass and food
      intake, whereas LD animals increasing body mass are resistant to leptin
      treatment. In the present study, we investigated whether seasonal changes in body
      mass could be linked to modulation of the leptin signal by suppressor of cytokine
      signalling-3 (SOCS3). We used in situ hybridisation to examine hypothalamic
      arcuate nucleus (ARC) expression of SOCS3, neuropeptide Y (NPY), agouti-related
      peptide (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine
      regulated transcript (CART) genes in 90 voles exposed to either SD or LD for up
      to 11 weeks. LD voles increasing body mass had significantly higher levels of
      SOCS3 mRNA than SD or LD voles with a stable body mass. There were no associated
      changes in expression of NPY, AgRP, POMC and CART genes. These results suggest
      that voles that regulate body mass at either the lower (SD) or upper (LD) plateau
      remain sensitive to leptin action, whereas SOCS3-mediated leptin resistance is a
      short-term mechanism that enables animals to move between the stable body mass
      plateaus. Our data provide evidence that expression of SOCS3 in the ARC is
      involved in the modulation of the strength of the leptin signal to facilitate
      seasonal cycles in body mass and adiposity.

PMID- 17214871
TI  - Bistability with hysteresis in the activity of vasopressin cells.
AB  - Magnocellular vasopressin neurones generate distinctive 'phasic' patterns of
      electrical activity during which periods of spiking activity (bursts) alternate
      with periods of no spikes or occasional spikes. The mechanisms of burst
      termination in vivo are still not clearly understood. We recorded from single
      phasic vasopressin cells in vivo and here we show that burst terminations in some
      phasic cells is preceded by transient increases in activity, consistent with
      bursts ending as a result of activity-dependent inhibition. We show that
      extrinsically imposed increases in activity, evoked by brief stimulation of the
      organum vasculosum of the lamina terminalis, can either trigger bursts if given
      when a cell is silent, or stop bursts if given when a cell is active. Thus, the
      magnocellular vasopressin system is a population of independent bistable
      oscillators. The population as a whole is insensitive to transient changes in
      input level, whether these are excitatory or inhibitory. The vasopressin cell
      population thus acts like a 'low-pass filter'; although brief large changes in
      input rate have little overall effect, the population responds very effectively
      to small, sustained changes in input rate by evolving a pattern of discharge
      activity that efficiently maintains secretion. We note that these filtering
      characteristics are the opposite of the filtering characteristics that are
      typically associated with neurones.

PMID- 17214872
TI  - Different neural melatonin-target tissues are critical for encoding and
      retrieving day length information in Siberian hamsters.
AB  - Siberian hamsters exhibit several seasonal rhythms in physiology and behaviour,
      including reproduction, energy balance, body mass, and pelage colouration.
      Unambiguous long- and short day lengths stimulate and inhibit reproduction,
      respectively. Whether gonadal growth or regression occurs in an intermediate day
      length (e.g. 14 h L : 10 h D; 14L), depends on whether the antecedent day lengths
      were shorter (10L) or longer (16L). Variations in day length are encoded by the
      duration of nocturnal pineal melatonin secretion, which is decoded at several
      neural melatonin target tissues to control testicular structure and function. We
      assessed participation of three such structures in the acquisition and retrieval
      of day length information. Elimination of melatonin signalling to the nucleus
      reuniens (NRe), but not to the suprachiasmatic nucleus (SCN) or paraventricular
      thalamus (PVt), interfered with the acquisition of a long day reproductive
      response, whereas the obscuring of melatonin signals to the SCN and the NRe, but
      not to the PVt, interfered with the photoperiod history response. The SCN and NRe
      contribute in different ways to the melatonin-based system that mediates seasonal
      rhythms in male reproduction.

PMID- 17214873
TI  - Mineralocorticoid pretreatment enhances angiotensin II-induced neuronal
      excitation but not salt drinking in male Fischer rats.
AB  - Central administration of angiotensin (Ang) II stimulates thirst and sodium
      intake via the AT-1 receptor. Mineralocorticoid pretreatment enhances Ang II
      induced drinking of hypertonic salt solutions (i.e. the synergy theory) in Wistar
      and Sprague-Dawley rats. Electrophysiological experiments using iontophoretic
      application of Ang II, and the AT-1 receptor specific nonpeptide antagonist
      losartan, have shown excitation of neurones in the preoptic/medial septum region
      of urethane anaesthetised male Wistar rats. Deoxycorticosterone acetate (DOCA)
      pretreatment further enhanced this neuronal excitation to Ang II and reduced the
      responses to losartan. This generated the hypothesis that DOCA-enhanced Ang II
      induced neuronal excitation was necessary for the enhanced salt intake of synergy
      theory. We tested this hypothesis in Fischer 344 rats that are known to have a
      low basal salt appetite and reduced sensitivity for i.c.v. Ang II. We compared
      the effect of DOCA pretreatment on i.c.v. Ang II-induced water and 2% NaCl intake
      in behaving adult male, Fischer rats, as well as preoptic/medial septum region
      neuronal responses to Ang II and losartan, using a seven-barrelled micro
      iontophoretic electrode sealed to a recording electrode in urethane
      anaesthetised, male Fischer rats. Two groups were used: one pretreated with DOCA
      (0.5 mg/day for 3 days) and the other comprising controls, treated with isotonic
      saline. Ang II applied iontophoretically increased activity in 31% of the
      spontaneously active neurones. Following DOCA pretreatment, the responsiveness to
      Ang II (when applied after aldosterone) was increased. By contrast, in the
      behaving animals, water and 2% NaCl intake in response to i.c.v. Ang II were not
      enhanced by DOCA pretreatment. These results do not support the working
      hypothesis but could be interpreted as evidence for the existence of two
      separately modulated central Ang II systems: one responding to mineralocorticoids
      with increased neuronal activity and the other responsible for the Ang II-induced
      sodium appetite in conscious rats.

PMID- 17214874
TI  - Social instability in adolescence alters the central and peripheral hypothalamic
      pituitary-adrenal responses to a repeated homotypic stressor in male and female
      rats.
AB  - There has been little research on effects of chronic stressors on neuroendocrine
      function in adolescence despite increasing evidence of enduring effects of
      stressors during this period on behaviour in adulthood. We previously reported
      that social stress (SS: daily 1 h isolation and new cage partner for 16 days) in
      adolescence altered locomotor responses to psychostimulants in adulthood. Here,
      we investigated neuroendocrine responses over the duration of the procedure that
      may underlie the enduring effects of SS. SS rats were compared to rats undergoing
      daily isolation only (ISO) and controls (CTL) to determine responses to acute and
      repeated isolation with and without social instability. At 30 days of age (first
      isolation), higher plasma corticosterone and corticotrophin-releasing hormone
      (CRH) mRNA expression in the paraventricular nucleus (PVN) of the hypothalamus
      and in the central nucleus of the amygdala (CeA) were found in males caged with a
      new partner (SS) after isolation than those returned to their original partner
      (ISO). On day 45, SS males and females showed less habituation (higher bioactive
      levels of corticosterone based on plasma corticosterone and corticosteroid
      binding globulin levels) to the 16th episode of isolation than did ISO. SS and
      ISO had higher baseline expression of CRH mRNA in the PVN on day 45 than did CTL,
      and only CTL had increased levels after isolation. CRH mRNA expression in the CeA
      increased to a first isolation in CTL and to a 16th isolation in SS but not in
      ISO males. Modest differences in social interactions were observed between SS and
      ISO when returned to their cages after isolation. The results suggest that mild
      social stressors in adolescence impede neuroendocrine adaptation to homotypic
      stressors. The resultant increase in exposure to glucocorticoids over adolescence
      may alter ongoing brain development and increase vulnerability to
      psychopathology.

PMID- 17214875
TI  - Circadian clocks: setting time by food.
AB  - In mammals, daily rhythms in behaviour and physiology are driven by a circadian
      timing system comprised, in a hierarchical way, of a master pacemaker in the
      suprachiasmatic nuclei (SCN) of the hypothalamus and of peripheral oscillators in
      most body cells. At the molecular level, in both the SCN and peripheral
      oscillators, the circadian clock mechanism is built from interconnected feedback
      loops in gene expression that operate in a cell-autonomous and self-sustained
      fashion. The SCN clock is mainly entrained by light/dark cycles. By contrast,
      peripheral oscillators can be strongly affected by daily feeding cycles, which
      have little effect on the phase of the SCN. However, when feeding schedules are
      coupled with a caloric restriction, behavioural and physiological circadian
      rhythms and gene expression in the SCN are shifted and/or entrained to meal-time.
      Moreover, the reward and motivational value of food can also be a potent
      synchroniser for the SCN clock. This suggests that energy metabolism and
      motivational properties of food can influence the clock mechanism of the SCN.
      Food-related cues may entrain clock genes of the SCN with a direct effect, or be
      mediated indirectly by another neural or peripheral site. In addition, there may
      be one or more oscillator sites that would play an integral role as a food
      entrained oscillator (FEO), responsible for anticipation of meal-time. The site
      housing, or the network underlying, this putative FEO is still unknown. The aim
      of this review is to summarise our current knowledge of the central and
      peripheral circadian clocks and how they can be entrained by feeding at the
      physiological and molecular levels.

PMID- 17214876
TI  - Neuronal activity of aromatase enzyme in non-copulating male rats.
AB  - There are apparently normal male rats that fail to initiate copulation; these
      animals are called non-copulating (NC) males. Several research groups have
      demonstrated that conversion of testosterone to oestradiol (aromatisation) in
      specific brain areas known to be involved in the control of masculine sexual
      behaviour is fundamental in the control of masculine sexual behaviour. The aim of
      the present study was to test the hypothesis that the concentration of aromatase
      activity (AA) in the brain is lower in NC males than in copulating males (C). We
      quantified AA in several brain nuclei and also evaluated whether NC rats have
      altered concentrations of testosterone in their plasma. We found that AA was
      reduced in the medial preoptic nuclei (MPN) of NC male rats vs C males. In
      addition, NC and C male rats had similar plasma levels of testosterone. These
      data suggest that reduced levels of AA in the MPN could be a crucial factor
      associated with lack of male coital behaviour in rats.

PMID- 17214877
TI  - Plastoglobules: a new address for targeting recombinant proteins in the
      chloroplast.
AB  - BACKGROUND: The potential of transgenic plants for cost-effective production of
      pharmaceutical molecules is now becoming apparent. Plants have the advantage over
      established fermentation systems (bacterial, yeast or animal cell cultures) to
      circumvent the risk of pathogen contamination, to be amenable to large scaling up
      and to necessitate only established farming procedures. Chloroplasts have proven
      a useful cellular compartment for protein accumulation owing to their large size
      and number, as well as the possibility for organellar transformation. They
      therefore represent the targeting destination of choice for recombinant proteins
      in leaf crops such as tobacco. Extraction and purification of recombinant
      proteins from leaf material contribute to a large extent to the production costs.
      Developing new strategies facilitating these processes is therefore necessary.
      RESULTS: Here, we evaluated plastoglobule lipoprotein particles as a new
      subchloroplastic destination for recombinant proteins. The yellow fluorescent
      protein as a trackable cargo was targeted to plastoglobules when fused to
      plastoglobulin 34 (PGL34) as the carrier. Similar to adipocyte differentiation
      related protein (ADRP) in animal cells, most of the protein sequence of PGL34 was
      necessary for targeting to lipid bodies. The recombinant protein was efficiently
      enriched in plastoglobules isolated by simple flotation centrifugation. The
      viability of plants overproducing the recombinant protein was not affected,
      indicating that plastoglobule targeting did not significantly impair
      photosynthesis or sugar metabolism. CONCLUSION: Our data identify plastoglobules
      as a new targeting destination for recombinant protein in leaf crops. The wide
      spread presence of plastoglobules and plastoglobulins in crop species promises
      applications comparable to those of transgenic oilbody-oleosin technology in
      molecular farming.

PMID- 17214878
TI  - Inter-population variability of DEFA3 gene absence: correlation with haplotype
      structure and population variability.
AB  - BACKGROUND: Copy number variants (CNVs) account for a significant proportion of
      normal phenotypic variation and may have an important role in human pathological
      variation. The alpha-defensin cluster on human chromosome 8p23.1 is one of the
      better-characterized CNVs, in which high copy number variability affecting the
      DEFA1 and DEFA3 genes has been reported. Moreover, the DEFA3 gene has been found
      to be absent in a significant proportion of control population subjects. CNVs
      involving immune genes, such as alpha-defensins, are possibly contributing to
      innate immunity differences observed between individuals and influence
      predisposition and susceptibility to disease. RESULTS: We have tested the DEFA3
      absence in 697 samples from different human populations. The proportion of
      subjects lacking DEFA3 has been found to vary from 10% to 37%, depending on the
      population tested, suggesting differences in innate immune function between
      populations. Absence of DEFA3 was correlated with the region's haplotype block
      structure. African samples showed a higher intra-populational variability
      together with the highest proportion of subjects without DEFA3 (37%). Association
      analysis of DEFA3 absence with 136 SNPs from a 100-kb region identified a
      conserved haplotype in the Caucasian population, extending for the whole region.
      CONCLUSION: Complexity and variability are essential genomic features of the
      alpha-defensin cluster at the 8p23.1 region. The identification of population
      differences in subjects lacking the DEFA3 gene may be suggestive of population
      specific selective pressures with potential impact on human health.

PMID- 17214879
TI  - Diagnostic pathology - editorial.

PMID- 17214880
TI  - IDconverter and IDClight: conversion and annotation of gene and protein IDs.
AB  - BACKGROUND: Researchers involved in the annotation of large numbers of gene,
      clone or protein identifiers are usually required to perform a one-by-one
      conversion for each identifier. When the field of research is one such as
      microarray experiments, this number may be around 30,000. RESULTS: To help
      researchers map accession numbers and identifiers among clones, genes, proteins
      and chromosomal positions, we have designed and developed IDconverter and
      IDClight. They are two user-friendly, freely available web server applications
      that also provide additional functional information by mapping the identifiers on
      to pathways, Gene Ontology terms, and literature references. Both tools are high
      throughput oriented and include identifiers for the most common genomic
      databases. These tools have been compared to other similar tools, showing that
      they are among the fastest and the most up-to-date. CONCLUSION: These tools
      provide a fast and intuitive way of enriching the information coming out of high
      throughput experiments like microarrays. They can be valuable both to wet-lab
      researchers and to bioinformaticians.

PMID- 17214881
TI  - Effects of hyaluronan treatment on lipopolysaccharide-challenged fibroblast-like
      synovial cells.
AB  - Numerous investigations have reported the efficacy of exogenous hyaluronan (HA)
      in modulating acute and chronic inflammation. The current study was performed to
      determine the in vitro effects of lower and higher molecular weight HA on
      lipopolysaccharide (LPS)-challenged fibroblast-like synovial cells. Normal
      synovial fibroblasts were cultured in triplicate to one of four groups: group 1,
      unchallenged; group 2, LPS-challenged (20 ng/ml); group 3, LPS-challenged
      following preteatment and sustained treatment with lower molecular weight HA; and
      group 4, LPS-challenged following pretreatment and sustained treatment with
      higher molecular weight HA. The response to LPS challenge and the influence of HA
      were compared among the four groups using cellular morphology scoring, cell
      number, cell viability, prostaglandin E2 (PGE2) production, IL-6 production,
      matrix metalloproteinase 3 (MMP3) production, and gene expression microarray
      analysis. As expected, our results demonstrated that LPS challenge induced a loss
      of characteristic fibroblast-like synovial cell culture morphology (P < 0.05),
      decreased the cell number (P < 0.05), increased PGE2 production 1,000-fold (P <
      0.05), increased IL-6 production 15-fold (P < 0.05), increased MMP3 production
      threefold (P < 0.05), and generated a profile of gene expression changes typical
      of LPS (P < 0.005). Importantly, LPS exposure at this concentration did not alter
      the cell viability. Higher molecular weight HA decreased the morphologic change
      (P < 0.05) associated with LPS exposure. Both lower and higher molecular weight
      HA significantly altered a similar set of 21 probe sets (P < 0.005), which
      represented decreased expression of inflammatory genes (PGE2, IL-6) and catabolic
      genes (MMP3) and represented increased expression of anti-inflammatory and
      anabolic genes. The molecular weight of the HA product did not affect the cell
      number, the cell viability or the PGE2, IL-6, or MMP3 production. Taken together,
      the anti-inflammatory and anticatabolic gene expression profiles of fibroblast
      like synovial cells treated with HA and subsequently challenged with LPS support
      the pharmacologic benefits of treatment with HA regardless of molecular weight.
      The higher molecular weight HA product provided a cellular protective effect not
      seen with the lower molecular weight HA product.

PMID- 17214884
TI  - Differential impact of simultaneous migration on coevolving hosts and parasites.
AB  - BACKGROUND: The dynamics of antagonistic host-parasite coevolution are believed
      to be crucially dependent on the rate of migration between populations. We
      addressed how the rate of simultaneous migration of host and parasite affected
      resistance and infectivity evolution of coevolving meta-populations of the
      bacterium Pseudomonas fluorescens and a viral parasite (bacteriophage). The
      increase in genetic variation resulting from small amounts of migration is
      expected to increase rates of adaptation of both host and parasite. However,
      previous studies suggest phages should benefit more from migration than bacteria;
      because in the absence of migration, phages are more genetically limited and have
      a lower evolutionary potential compared to the bacteria. RESULTS: The results
      supported the hypothesis: migration increased the resistance of bacteria to their
      local (sympatric) hosts. Moreover, migration benefited phages more than hosts
      with respect to 'global' (measured with respect to the whole range of migration
      regimes) patterns of resistance and infectivity, because of the differential
      evolutionary responses of bacteria and phage to different migration regimes.
      Specifically, we found bacterial global resistance peaked at intermediate rates
      of migration, whereas phage global infectivity plateaued when migration rates
      were greater than zero. CONCLUSION: These results suggest that simultaneous
      migration of hosts and parasites can dramatically affect the interaction of host
      and parasite. More specifically, the organism with the lower evolutionary
      potential may gain the greater evolutionary advantage from migration.

PMID- 17214883
TI  - Energetics of the protein-DNA-water interaction.
AB  - BACKGROUND: To understand the energetics of the interaction between protein and
      DNA we analyzed 39 crystallographically characterized complexes with the HINT
      (Hydropathic INTeractions) computational model. HINT is an empirical free energy
      force field based on solvent partitioning of small molecules between water and 1
      octanol. Our previous studies on protein-ligand complexes demonstrated that free
      energy predictions were significantly improved by taking into account the
      energetic contribution of water molecules that form at least one hydrogen bond
      with each interacting species. RESULTS: An initial correlation between the
      calculated HINT scores and the experimentally determined binding free energies in
      the protein-DNA system exhibited a relatively poor r2 of 0.21 and standard error
      of +/- 1.71 kcal mol-1. However, the inclusion of 261 waters that bridge protein
      and DNA improved the HINT score-free energy correlation to an r2 of 0.56 and
      standard error of +/- 1.28 kcal mol-1. Analysis of the water role and energy
      contributions indicate that 46% of the bridging waters act as linkers between
      amino acids and nucleotide bases at the protein-DNA interface, while the
      remaining 54% are largely involved in screening unfavorable electrostatic
      contacts. CONCLUSION: This study quantifies the key energetic role of bridging
      waters in protein-DNA associations. In addition, the relevant role of hydrophobic
      interactions and entropy in driving protein-DNA association is indicated by
      analyses of interaction character showing that, together, the favorable polar and
      unfavorable polar/hydrophobic-polar interactions (i.e., desolvation) mostly
      cancel.

PMID- 17214885
TI  - A polymorphism in the 3' untranslated region of the gene encoding prostaglandin
      endoperoxide synthase 2 is not associated with an increase in breast cancer risk:
      a nested case-control study.
AB  - INTRODUCTION: Prostaglandins are integral components in the cellular response to
      inflammation, promoting cellular proliferation and angiogenesis. The enzyme
      responsible for the conversion of arachidonic acid to prostaglandins in response
      to inflammation is prostaglandin endoperoxide synthase 2/cyclo-oxygenase 2
      (PTGS2/COX2). Polymorphisms in the PTGS2 gene have been associated with various
      diseases, including inflammatory bowel disease and cancer of the lung,
      colorectum, and breast. METHODS: We genotyped the five most common polymorphisms
      (rs20417, rs5277, rs20432, rs5275, and rs4648298) in the Nurses' Health Study
      (1,270 cases, 1,762 controls) to test the hypothesis that polymorphisms in PTGS2
      are associated with breast cancer risk, using logistic regression analyses. The
      Nurses' Health Study 2 (317 cases, 634 controls) and Harvard Women's Health Study
      (702 cases, 703 controls) were used to further examine putative associations.
      RESULTS: The rs5275 polymorphism in the 3' untranslated region of the PTGS2 gene
      was associated with a decrease in breast cancer risk. We therefore genotyped this
      single-nucleotide polymorphism in the Nurses' Health Study 2 and Harvard Women's
      Health Study. Similar results were observed in these subsequent analyses, with no
      statistically significant heterogeneity in risk estimates between studies. In
      pooled analyses, women homozygous for the T allele at rs5275 had a 20% lower risk
      of breast cancer than those homozygous for the C allele (odds ratio 0.80, 95%
      confidence interval 0.66 to 0.97). CONCLUSION: Although this polymorphism may be
      associated with a decrease in breast cancer risk among Caucasian women, we
      provide strong evidence that it is not associated with an increased risk of
      breast cancer.

PMID- 17214886
TI  - Negative consequences associated with dependence in daily cannabis users.
AB  - BACKGROUND: Cannabis is the most widely consumed illicit substance in America,
      with increasing rates of use. Some theorists tend to link frequency of use with
      cannabis dependence. Nevertheless, fewer than half of daily cannabis users meet
      DSM-IV-TR criteria for cannabis dependence. This study seeks to determine whether
      the negative aspects associated with cannabis use can be explained by a proxy
      measure of dependence instead of by frequency of use. RESULTS: Over 2500 adult
      daily cannabis users completed an Internet survey consisting of measures of
      cannabis and other drug use, in addition to measures of commonly reported
      negative problems resulting from cannabis use. We compared those who met a proxy
      measure of DSM-IV-TR criteria for cannabis dependence (N = 1111) to those who did
      not meet the criteria (N = 1770). Cannabis dependent subjects consumed greater
      amounts of cannabis, alcohol, and a variety of other drugs. They also had lower
      levels of motivation, happiness, and satisfaction with life, with higher levels
      of depression and respiratory symptoms. CONCLUSION: Although all of our subjects
      reported daily use, only those meeting proxy criteria for cannabis dependence
      reported significant associated problems. Our data suggest that dependence need
      not arise from daily use, but consuming larger amounts of cannabis and other
      drugs undoubtedly increases problems.

PMID- 17214888
TI  - Relemed: sentence-level search engine with relevance score for the MEDLINE
      database of biomedical articles.
AB  - BACKGROUND: Receiving extraneous articles in response to a query submitted to
      MEDLINE/PubMed is common. When submitting a multi-word query (which is the
      majority of queries submitted), the presence of all query words within each
      article may be a necessary condition for retrieving relevant articles, but not
      sufficient. Ideally a relationship between the query words in the article is also
      required. We propose that if two words occur within an article, the probability
      that a relation between them is explained is higher when the words occur within
      adjacent sentences versus remote sentences. Therefore, sentence-level concurrence
      can be used as a surrogate for existence of the relationship between the words.
      In order to avoid the irrelevant articles, one solution would be to increase the
      search specificity. Another solution is to estimate a relevance score to sort the
      retrieved articles. However among the >30 retrieval services available for
      MEDLINE, only a few estimate a relevance score, and none detects and incorporates
      the relation between the query words as part of the relevance score. RESULTS: We
      have developed "Relemed", a search engine for MEDLINE. Relemed increases
      specificity and precision of retrieval by searching for query words within
      sentences rather than the whole article. It uses sentence-level concurrence as a
      statistical surrogate for the existence of relationship between the words. It
      also estimates a relevance score and sorts the results on this basis, thus
      shifting irrelevant articles lower down the list. In two case studies, we
      demonstrate that the most relevant articles appear at the top of the Relemed
      results, while this is not necessarily the case with a PubMed search. We have
      also shown that a Relemed search includes not only all the articles retrieved by
      PubMed, but potentially additional relevant articles, due to the extended
      'automatic term mapping' and text-word searching features implemented in Relemed.
      CONCLUSION: By using sentence-level matching, Relemed can deliver higher
      specificity, thus eliminating more false-positive articles. By introducing an
      appropriate relevance metric, the most relevant articles on which the user wishes
      to focus are listed first. Relemed also shrinks the displayed text, and hence the
      time spent scanning the articles.

PMID- 17214887
TI  - Expression of the Na+/I- symporter (NIS) is markedly decreased or absent in
      gastric cancer and intestinal metaplastic mucosa of Barrett esophagus.
AB  - BACKGROUND: The sodium/iodide symporter (NIS) is a plasma membrane glycoprotein
      that mediates iodide (I-) transport in the thyroid, lactating breast, salivary
      glands, and stomach. Whereas NIS expression and regulation have been extensively
      investigated in healthy and neoplastic thyroid and breast tissues, little is
      known about NIS expression and function along the healthy and diseased
      gastrointestinal tract. METHODS: Thus, we investigated NIS expression by
      immunohistochemical analysis in 155 gastrointestinal tissue samples and by
      immunoblot analysis in 17 gastric tumors from 83 patients. RESULTS: Regarding the
      healthy Gl tract, we observed NIS expression exclusively in the basolateral
      region of the gastric mucin-producing epithelial cells. In gastritis, positive
      NIS staining was observed in these cells both in the presence and absence of
      Helicobacter pylori. Significantly, NIS expression was absent in gastric cancer,
      independently of its histological type. Only focal faint NIS expression was
      detected in the direct vicinity of gastric tumors, i.e., in the histologically
      intact mucosa, the expression becoming gradually stronger and linear farther away
      from the tumor. Barrett mucosa with junctional and fundic-type columnar
      metaplasia displayed positive NIS staining, whereas Barrett mucosa with
      intestinal metaplasia was negative. NIS staining was also absent in
      intestinalized gastric polyps. CONCLUSION: That NIS expression is markedly
      decreased or absent in case of intestinalization or malignant transformation of
      the gastric mucosa suggests that NIS may prove to be a significant tumor marker
      in the diagnosis and prognosis of gastric malignancies and also precancerous
      lesions such as Barrett mucosa, thus extending the medical significance of NIS
      beyond thyroid disease.

PMID- 17214889
TI  - MAP kinase meets mitosis: a role for Raf Kinase Inhibitory Protein in spindle
      checkpoint regulation.
AB  - Raf Kinase Inhibitory Protein (RKIP) is an evolutionarily conserved protein that
      functions as a modulator of signaling by the MAP kinase cascade. Implicated as a
      metastasis suppressor, Raf Kinase Inhibitory Protein depletion correlates with
      poor prognosis for breast, prostate and melanoma tumors but the mechanism is
      unknown. Recent evidence indicates that Raf Kinase Inhibitory Protein regulates
      the mitotic spindle assembly checkpoint by controlling Aurora B Kinase activity,
      and the mechanism involves Raf/MEK/ERK signaling. In contrast to elevated MAP
      kinase signaling during the G1, S or G2 phases of the cell cycle that activates
      checkpoints and induces arrest or senescence, loss of RKIP during M phase leads
      to bypass of the spindle assembly checkpoint and the generation of chromosomal
      abnormalities. These results reveal a role for Raf Kinase Inhibitory Protein and
      the MAP kinase cascade in ensuring the fidelity of chromosome segregation prior
      to cell division. Furthermore, these data highlight the need for precise
      titration of the MAP kinase signal to ensure the integrity of the spindle
      assembly process and provide a mechanism for generating genomic instability in
      tumors. Finally, these results raise the possibility that RKIP status in tumors
      could influence the efficacy of treatments such as poisons that stimulate the
      Aurora B-dependent spindle assembly checkpoint.

PMID- 17214890
TI  - Electrophysiological evidence for notation independence in numerical processing.
AB  - BACKGROUND: A dominant view in numerical cognition is that numerical comparisons
      operate on a notation independent representation (Dehaene, 1992). Although
      previous human neurophysiological studies using scalp-recorded event-related
      potentials (ERPs) on the numerical distance effect have been interpreted as
      supporting this idea, differences in the electrophysiological correlates of the
      numerical distance effect in symbolic notations (e.g. Arabic numerals) and non
      symbolic notations (e.g. a set of visually presented dots of a certain number)
      are not entirely consistent with this view. METHODS AND RESULTS: Two experiments
      were conducted to resolve these discrepancies. In Experiment 1, participants
      performed a symbolic and a non-symbolic numerical comparison task ("smaller or
      larger than 5?") with numerical values 1-4 and 6-9 while ERPs were recorded.
      Consistent with a previous report (Temple & Posner, 1998), in the symbolic
      condition the amplitude of the P2p ERP component (210-250 ms post-stimulus) was
      larger for values near to the standard than for values far from the standard
      whereas this pattern was reversed in the non-symbolic condition. However, closer
      analysis indicated that the reversal in polarity was likely due to the presence
      of a confounding stimulus effect on the early sensory ERP components for small
      versus larger numerical values in the non-symbolic condition. In Experiment 2
      exclusively large numerosities (8-30) were used, thereby rendering sensory
      differences negligible, and with this control in place the numerical distance
      effect in the non-symbolic condition mirrored the symbolic condition of
      Experiment 1. CONCLUSION: Collectively, the results support the claim of an
      abstract semantic processing stage for numerical comparisons that is independent
      of input notation.

PMID- 17214891
TI  - Medical communication and technology: a video-based process study of the use of
      decision aids in primary care consultations.
AB  - BACKGROUND: Much of the research on decision-making in health care has focused on
      consultation outcomes. Less is known about the process by which clinicians and
      patients come to a treatment decision. This study aimed to quantitatively
      describe the behaviour shown by doctors and patients during primary care
      consultations when three types of decision aids were used to promote treatment
      decision-making in a randomised controlled trial. METHODS: A video-based study
      set in an efficacy trial which compared the use of paper-based guidelines
      (control) with two forms of computer-based decision aids (implicit and explicit
      versions of DARTS II). Treatment decision concerned warfarin anti-coagulation to
      reduce the risk of stroke in older patients with atrial fibrillation. Twenty nine
      consultations were video-recorded. A ten-minute 'slice' of the consultation was
      sampled for detailed content analysis using existing interaction analysis
      protocols for verbal behaviour and ethological techniques for non-verbal
      behaviour. RESULTS: Median consultation times (quartiles) differed significantly
      depending on the technology used. Paper-based guidelines took 21 (19-26) minutes
      to work through compared to 31 (16-41) minutes for the implicit tool; and 44 (39
      55) minutes for the explicit tool. In the ten minutes immediately preceding the
      decision point, GPs dominated the conversation, accounting for 64% (58-66%) of
      all utterances and this trend was similar across all three arms of the trial.
      Information-giving was the most frequent activity for both GPs and patients,
      although GPs did this at twice the rate compared to patients and at higher rates
      in consultations involving computerised decision aids. GPs' language was highly
      technically focused and just 7% of their conversation was socio-emotional in
      content; this was half the socio-emotional content shown by patients (15%).
      However, frequent head nodding and a close mirroring in the direction of eye-gaze
      suggested that both parties were active participants in the conversation
      CONCLUSION: Irrespective of the arm of the trial, both patients' and GPs'
      behaviour showed that they were reciprocally engaged in these consultations.
      However, even in consultations aimed at promoting shared decision-making, GPs'
      were verbally dominant, and they worked primarily as information providers for
      patients. In addition, computer-based decision aids significantly prolonged the
      consultations, particularly the later phases. These data suggest that decision
      aids may not lead to more 'sharing' in treatment decision-making and that, in
      their current form, they may take too long to negotiate for use in routine
      primary care.

PMID- 17214892
TI  - Examining impulsivity as an endophenotype using a behavioral approach: a DRD2
      TaqI A and DRD4 48-bp VNTR association study.
AB  - BACKGROUND: Research on the genetic basis for impulsivity has revealed an array
      of ambiguous findings. This may be a result of limitations to self-report
      assessments of impulsivity. Behavioral measures that assess more narrowly defined
      aspects of impulsivity may clarify genetic influences. This study examined the
      relationship between possession of the DRD2 TaqI A and DRD4 48 bp VNTR genetic
      polymorphisms and performance on a behavioral measure of impulsivity, the delay
      discounting task (DDT), and three traditional self-report measures. METHODS: 195
      individuals (42% male) were recruited from a university campus and were assessed
      in small group sessions using personal computers. Genotyping was conducted using
      previously established protocols. For the DRD2 TaqI A locus, individuals were
      designated as possessing at least one copy of the A1 allele (A1+) or not (A1-),
      and for the DRD4 48-bp VNTR locus, individuals were designated as having at least
      one long allele (7 repeats or longer, L+) or not (L-). Principal analyses used
      multiple univariate factorial 2 (A1+/A1-) x 2 (L+/L-) analyses of variance.
      RESULTS: A significant main effect of A1+ status on DDT performance was evident
      (p = .006) as well as a significant interaction effect (p = .006) between both
      genes. No other significant effects were evident on the self-report measures,
      with the exception of a trend toward an interaction effect on the Sensation
      Seeking Scale. Exploratory analyses suggested that the significant effects were
      not a function of population stratification or gender. DISCUSSION: These data
      suggest that the DRD2 TaqI A and DRD4 VNTR polymorphisms influence impulsivity as
      measured with a delay discounting task. Specifically, these findings suggest that
      an interaction between the functional effects of the two unlinked genotypes
      results in significant difference in the balance of mesolimbic dopaminergic
      activation relative to frontal-parietal activation. However, these findings are
      also the first in this area and must be replicated. CONCLUSION: These findings
      suggest a meaningful interaction between the DRD2 TaqI A and DRD4 VNTR
      polymorphisms in the expression of impulsivity and provide initial support for
      the utility of using behavioral measures for clarifying genetic influences on
      impulsivity.

PMID- 17214894
TI  - Functional analysis of Arabidopsis WRKY25 transcription factor in plant defense
      against Pseudomonas syringae.
AB  - BACKGROUND: A common feature of plant defense responses is the transcriptional
      regulation of a large number of genes upon pathogen infection or treatment with
      pathogen elicitors. A large body of evidence suggests that plant WRKY
      transcription factors are involved in plant defense including transcriptional
      regulation of plant host genes in response to pathogen infection. However, there
      is only limited information about the roles of specific WRKY DNA-binding
      transcription factors in plant defense. RESULTS: We analyzed the role of the
      WRKY25 transcription factor from Arabidopsis in plant defense against the
      bacterial pathogen Pseudomonas syringae. WRKY25 protein recognizes the TTGACC W
      box sequences and its translational fusion with green fluorescent protein is
      localized to the nucleus. WRKY25 expression is responsive to general
      environmental stress. Analysis of stress-induced WRKY25 in the defense signaling
      mutants npr1, sid2, ein2 and coi1 further indicated that this gene is positively
      regulated by the salicylic acid (SA) signaling pathway and negatively regulated
      by the jasmonic acid signaling pathway. Two independent T-DNA insertion mutants
      for WRKY25 supported normal growth of a virulent strain of P. syringae but
      developed reduced disease symptoms after infection. By contrast, Arabidopsis
      constitutively overexpressing WRKY25 supported enhanced growth of P. syringae and
      displayed increased disease symptom severity as compared to wild-type plants.
      These WRKY25-overexpressing plants also displayed reduced expression of the SA
      regulated PR1 gene after the pathogen infection, despite normal levels of free
      SA. CONCLUSION: The nuclear localization and sequence-specific DNA-binding
      activity support that WRKY25 functions as a transcription factor. Based on
      analysis of both T-DNA insertion mutants and transgenic overexpression lines,
      stress-induced WRKY25 functions as a negative regulator of SA-mediated defense
      responses to P. syringae. This proposed role is consistent with the recent
      finding that WRKY25 is a substrate of Arabidopsis MAP kinase 4, a repressor of SA
      dependent defense responses.

PMID- 17214893
TI  - Phylogenetic distribution of translational GTPases in bacteria.
AB  - BACKGROUND: Translational GTPases are a family of proteins in which GTPase
      activity is stimulated by the large ribosomal subunit. Conserved sequence
      features allow members of this family to be identified. RESULTS: To achieve
      accurate protein identification and grouping we have developed a method combining
      searches with Hidden Markov Model profiles and tree based grouping. We found all
      the genes for translational GTPases in 191 fully sequenced bacterial genomes. The
      protein sequences were grouped into nine subfamilies. Analysis of the results
      shows that three translational GTPases, the translation factors EF-Tu, EF-G and
      IF2, are present in all organisms examined. In addition, several copies of the
      genes encoding EF-Tu and EF-G are present in some genomes. In the case of
      multiple genes for EF-Tu, the gene copies are nearly identical; in the case of
      multiple EF-G genes, the gene copies have been considerably diverged. The fourth
      translational GTPase, LepA, the function of which is currently unknown, is also
      nearly universally conserved in bacteria, being absent from only one organism out
      of the 191 analyzed. The translation regulator, TypA, is also present in most of
      the organisms examined, being absent only from bacteria with small
      genomes.Surprisingly, some of the well studied translational GTPases are present
      only in a very small number of bacteria. The translation termination factor RF3
      is absent from many groups of bacteria with both small and large genomes. The
      specialized translation factor for selenocysteine incorporation--SelB--was found
      in only 39 organisms. Similarly, the tetracycline resistance proteins (Tet) are
      present only in a small number of species. Proteins of the CysN/NodQ subfamily
      have acquired functions in sulfur metabolism and production of signaling
      molecules. The genes coding for CysN/NodQ proteins were found in 74 genomes. This
      protein subfamily is not confined to Proteobacteria, as suggested previously but
      present also in many other groups of bacteria. CONCLUSION: Four of the
      translational GTPase subfamilies (IF2, EF-Tu, EF-G and LepA) are represented by
      at least one member in each bacterium studied, with one exception in LepA. This
      defines the set of translational GTPases essential for basic cell functions.

PMID- 17214895
TI  - Extended abdominoperineal resection in women: the Barbadian experience.
AB  - BACKGROUND AND OBJECTIVES: We report our results of a selective approach to
      primary direct appositional vaginal repair versus transverse rectus abdominis
      flap repair (TRAM) in patients with extensive rectal/anal cancer or in cases with
      primary cancer of cervix, vagina or vulva involving the anal canal and anal
      sphincters. METHODS: Eighteen female patients (mean age: 62.9 years; range: 44-81
      years) with a median follow-up of 14 months (range: 2-36 months) undergoing
      extended abdominoperineal reconstruction with total mesorectal excision between
      May 2002 and September 2005, were studied. RESULTS: Twelve patients underwent an
      extended abdominoperineal resection with hysterectomy and vaginectomy, with 6
      patients undergoing primary TRAM flap reconstruction following pelvic
      exenteration. Exenterative procedures were performed in 2 cases of primary
      vaginal cancer, following Wertheim hysterectomy for carcinoma of the cervix with
      recurrence after radiation and in 2 further cases of anal cancer with extensive
      pelvic recurrence after primary chemoradiation. Fifteen cases are alive on follow
      up with no evidence of disease; 2 patients who had recurrent carcinoma of the
      cervix and who underwent TRAM flap reconstruction, have recurrent disease after 5
      and 6 months of follow-up, respectively. DISCUSSION: Our experience shows that
      careful primary closure of an extended abdominoperineal resection wound is
      effective and safe. Our one case of wound breakdown after primary repair
      underwent external beam and intracavitary irradiation primarily with wound
      breakdown of a primary repair followed by a delayed pedicled graciloplasty. TRAM
      flap reconstruction has been reserved in our unit for patients undergoing total
      pelvic extenteration. In general, we would recommend the use of TRAM flap
      reconstruction in younger sexually active patients where there has been external
      irradiation combined with brachytherapy.

PMID- 17214896
TI  - Emergency correction of coagulation before major surgery in two elderly patients
      on oral anticoagulation.
AB  - Recommendations for urgent reversal of oral anticoagulation with vitamin K1
      antagonists are largely derived from case series employing empirical dosing
      regimens with vitamin K1 and prothrombin complex concentrates. Data on the use of
      prothrombin complex concentrates in this indication are scarce in the elderly who
      are at high risk of both hemorrhagic and thrombotic complications. The two cases
      presented here describe patients older than 75 years who underwent rapid
      International Normalized Ratio (INR) reversal with prothrombin complex
      concentrates for surgical treatment of a bleeding ruptured spleen and for
      emergency surgery of a dissecting aorta. Both patients had their INRs rapidly
      corrected to <or= 1.6 and underwent operation without complications. Evidence on
      treatment of patients who present with elevated INR and who have major bleeding
      or need to undergo emergency surgery is based mainly on observational studies.
      The two elderly patients presented here underwent successful emergency surgery
      after their INRs had been corrected with the intravenous use of vitamin K1 in
      combination with prothrombin complex concentrate that was administered according
      to current guideline recommendations.

PMID- 17214897
TI  - The impact of vitamin D status on changes in bone mineral density during
      treatment with bisphosphonates and after discontinuation following long-term use
      in post-menopausal osteoporosis.
AB  - BACKGROUND: It is still unclear whether addition of calcium/vitamin D supplements
      leads to an incremental benefit in patients taking bisphosphonates and whether
      achievement of serum level of 25 (OH) vitamin D of at least 70 nmol/L has an
      impact on the skeletal response to bisphosphonates. Moreover the maintenance of
      BMD after bisphosphonates withdrawal with the continuation of calcium/vitamin D
      supplements only, remains uncertain. The aims were to assess the impact of
      vitamin D status on changes in bone mineral density (BMD) in firstly patients
      with post-menopausal osteoporosis on bisphosphonates and secondly following
      discontinuation of bisphosphonates after long-term use. METHODS: Two patient
      groups were recruited. The first study population comprised of 112 women treated
      with a bisphosphonate. The second study population consisted of 35 women who had
      been on bisphosphonates for > 5 years in whom the treatment agent was
      discontinued. Baseline BMD, changes in BMD following treatment, duration of
      treatment, serum 25 (OH) vitamin D, parathyroid hormone (PTH), urine C-terminal
      telopeptides of type 1 collagen (CTX) were obtained on the study participants.
      RESULTS: In the first study group, subjects with serum vitamin D concentrations
      (> 70 nmol/L) had a significantly lower serum PTH level (mean [SEM] 41 2 ng/L).
      PTH concentrations of 41 ng/L or less was associated with a significantly higher
      increase in BMD at the hip following treatment with bisphosphonates compared to
      patients with PTH > 41 ng/L (2.5% [0.9] v/s -0.2% [0.9], P = 0.04). In the second
      study group, discontinuation of bisphosphonate for 15 months after long-term
      treatment did not result in significant bone loss at the lumbar spine and total
      hip, although a trend towards gradual decline in BMD at the femoral neck was
      observed. CONCLUSION: the data suggest that optimal serum 25 (OH) vitamin D
      concentration may lead to further reduction in bone loss at the hip in patients
      on bisphosphonates. A prospective controlled trial is needed to evaluate whether
      the response to bisphosphonates is influenced by vitamin D status. BMD is
      preserved at the lumbar spine and total hip following discontinuation of
      bisphosphonate for a short period following long-term treatment, although a
      gradual loss occurs at the femoral neck.

PMID- 17214898
TI  - Bioinformatics analysis of the early inflammatory response in a rat thermal
      injury model.
AB  - BACKGROUND: Thermal injury is among the most severe forms of trauma and its
      effects are both local and systemic. Response to thermal injury includes cellular
      protection mechanisms, inflammation, hypermetabolism, prolonged catabolism, organ
      dysfunction and immuno-suppression. It has been hypothesized that gene expression
      patterns in the liver will change with severe burns, thus reflecting the role the
      liver plays in the response to burn injury. Characterizing the molecular
      fingerprint (i.e., expression profile) of the inflammatory response resulting
      from burns may help elucidate the activated mechanisms and suggest new
      therapeutic intervention. In this paper we propose a novel integrated framework
      for analyzing time-series transcriptional data, with emphasis on the burn-induced
      response within the context of the rat animal model. Our analysis robustly
      identifies critical expression motifs, indicative of the dynamic evolution of the
      inflammatory response and we further propose a putative reconstruction of the
      associated transcription factor activities. RESULTS: Implementation of our
      algorithm on data obtained from an animal (rat) burn injury study identified 281
      genes corresponding to 4 unique profiles. Enrichment evaluation upon both gene
      ontologies and transcription factors, verifies the inflammation-specific
      character of the selections and the rationalization of the burn-induced
      inflammatory response. Conducting the transcription network reconstruction and
      analysis, we have identified transcription factors, including AHR, Octamer
      Binding Proteins, Kruppel-like Factors, and cell cycle regulators as being highly
      important to an organism's response to burn response. These transcription factors
      are notable due to their roles in pathways that play a part in the gross
      physiological response to burn such as changes in the immune response and
      inflammation. CONCLUSION: Our results indicate that our novel
      selection/classification algorithm has been successful in selecting out genes
      with play an important role in thermal injury. Additionally, we have demonstrated
      the value of an integrative approach in identifying possible points of
      intervention, namely the activation of certain transcription factors that govern
      the organism's response.

PMID- 17214899
TI  - Psychiatric disorder criteria and their application to research in different
      racial groups.
AB  - BACKGROUND: The advent of standardized classification and assessment of
      psychiatric disorders, and considerable joint efforts among many countries has
      led to the reporting of international rates of psychiatric disorders, and
      inevitably, their comparison between different racial groups. RESULTS: In
      neurologic diseases with defined genetic etiologies, the same genetic cause has
      different phenotypes in different racial groups. CONCLUSION: We suggest that
      genetic differences between races mean that diagnostic criteria refined in one
      racial group, may not be directly and simply applicable to other racial groups
      and thus more effort needs to be expended on defining diseases in other groups.
      Cross-racial confounds (in addition to cultural confounds) make the
      interpretation of rates in different groups even more hazardous than seems to
      have been appreciated.

PMID- 17214900
TI  - Microsurgical technique in obstetric brachial plexus repair: a personal
      experience in 200 cases over 10 years.
AB  - We present our personal operative technique in exposing and repairing obstetric
      brachial plexus (obp) lesions. This technical description of the operative
      procedure and the strategic choice for the neurotisations are analysed with
      special regards on the follow-up of these patients (always performed by the
      surgeon), the histological quality of the proximal root stumps used for cable
      grafting, and the general reconstruction principles established in international
      workshops. We would like to encourage debate on these detailed considerations
      wherever they could affect the functional outcome.

PMID- 17214901
TI  - Low prevalence of significant carotid artery disease in Iranian patients
      undergoing elective coronary artery bypass.
AB  - BACKGROUND: Coronary artery bypass grafting ranks as one of the most frequent
      operations worldwide. The presence of carotid artery stenosis may increase the
      stroke rate in the perioperative period. Routine preoperative noninvasive
      assessment of the carotid arteries are recommended in many institutions to reduce
      the stroke rate. METHODS: 271 consecutive patients undergoing coronary artery
      bypass grafting at Shaheed Madani hospital of Tabriz, Iran (age, 58.5 Y; 73.1%
      male) underwent preoperative ultrasonography for assessment of carotid artery
      wall thickness. RESULTS: Plaque in right common, left common, right internal and
      left internal carotid arteries was detected in 4.8%, 7.4%, 43.2% and 42.1% of
      patients respectively. 5 patients (1.8%) had significant (<50%) and 3 (1.1%)
      patients had critical (<70%) stenosis in internal carotid arteries. Plaque
      formation in common carotid was not significantly different between two genders
      but the stenosis of left internal carotid was more frequently seen among men.
      Patients with plaques in right or left internal carotid arteries were
      significantly older. CONCLUSION: Consecutive Iranian patients undergoing elective
      coronary artery bypass surgery show a very low prevalence of significant carotid
      artery disease.

PMID- 17214902
TI  - Mouse preimplantation embryo responses to culture medium osmolarity include
      increased expression of CCM2 and p38 MAPK activation.
AB  - BACKGROUND: Mechanisms that confer an ability to respond positively to
      environmental osmolarity are fundamental to ensuring embryo survival during the
      preimplantation period. Activation of p38 mitogen-activated protein kinase (MAPK)
      occurs following exposure to hyperosmotic treatment. Recently, a novel
      scaffolding protein called Osmosensing Scaffold for MEKK3 (OSM) was linked to p38
      MAPK activation in response to sorbitol-induced hypertonicity. The human ortholog
      of OSM is cerebral cavernous malformation 2 (CCM2). The present study was
      conducted to investigate whether CCM2 is expressed during mouse preimplantation
      development and to determine whether this scaffolding protein is associated with
      p38 MAPK activation following exposure of preimplantation embryos to hyperosmotic
      environments. RESULTS: Our results indicate that Ccm2 along with upstream p38
      MAPK pathway constituents (Map3k3, Map2k3, Map2k6, and Map2k4) are expressed
      throughout mouse preimplantation development. CCM2, MAP3K3 and the phosphorylated
      forms of MAP2K3/MAP2K6 and MAP2K4 were also detected throughout preimplantation
      development. Embryo culture in hyperosmotic media increased p38 MAPK activity in
      conjunction with elevated CCM2 levels. CONCLUSION: These results define the
      expression of upstream activators of p38 MAPK during preimplantation development
      and indicate that embryo responses to hyperosmotic environments include elevation
      of CCM2 and activation of p38 MAPK.

PMID- 17214903
TI  - Modeling the probability distribution of positional errors incurred by
      residential address geocoding.
AB  - BACKGROUND: The assignment of a point-level geocode to subjects' residences is an
      important data assimilation component of many geographic public health studies.
      Often, these assignments are made by a method known as automated geocoding, which
      attempts to match each subject's address to an address-ranged street segment
      georeferenced within a streetline database and then interpolate the position of
      the address along that segment. Unfortunately, this process results in positional
      errors. Our study sought to model the probability distribution of positional
      errors associated with automated geocoding and E911 geocoding. RESULTS:
      Positional errors were determined for 1423 rural addresses in Carroll County,
      Iowa as the vector difference between each 100%-matched automated geocode and its
      true location as determined by orthophoto and parcel information. Errors were
      also determined for 1449 60%-matched geocodes and 2354 E911 geocodes. Huge (> 15
      km) outliers occurred among the 60%-matched geocoding errors; outliers occurred
      for the other two types of geocoding errors also but were much smaller. E911
      geocoding was more accurate (median error length = 44 m) than 100%-matched
      automated geocoding (median error length = 168 m). The empirical distributions of
      positional errors associated with 100%-matched automated geocoding and E911
      geocoding exhibited a distinctive Greek-cross shape and had many other
      interesting features that were not capable of being fitted adequately by a single
      bivariate normal or t distribution. However, mixtures of t distributions with two
      or three components fit the errors very well. CONCLUSION: Mixtures of bivariate t
      distributions with few components appear to be flexible enough to fit many
      positional error datasets associated with geocoding, yet parsimonious enough to
      be feasible for nascent applications of measurement-error methodology to spatial
      epidemiology.

PMID- 17214904
TI  - Importance of A-loop complementarity with tRNAHis anticodon for continued
      selection of tRNAHis as the HIV reverse transcription primer.
AB  - BACKGROUND: Human immunodeficiency virus (HIV-1) preferentially selects tRNALys,3
      as the primer for reverse transcription. HIV-1 can be forced to select
      alternative tRNAs through mutation in the primer-binding site (PBS) and a region
      upstream of the PBS designated as the A-loop. Alteration of the PBS and A-loop to
      be complementary to the 3' terminal nucleotides and anticodon of tRNAHis results
      in HIV-1 that can stably utilize this tRNA for replication. RESULTS: In the
      current study, we have investigated the effect that mutations within the A-loop
      have on the stability of HIV-1 with a PBS complementary to tRNAHis. For these
      studies, we have altered the A-loop to be complementary to tRNAMet, tRNAGln,
      tRNAIle, tRNAThr and tRNASer. All substitutions of the A-loops with the PBS
      complementary to tRNAHis resulted in a reduction of infectious virus obtained
      following transfection of proviral genomes in the 293T cells. Virus replication
      in SupT1 cells was also impaired as a result of the alteration of the A-loop.
      Viruses with the A-loop complementary to tRNALys,3 and tRNASer reverted to
      utilize tRNALys,3 following in vitro replication. In contrast, viruses with the A
      loop complementary to the other tRNAs remained stable and continued to use
      tRNAHis. RNA modeling of the stem-loop structure revealed that nucleotides were
      displayed on the loop region that could potentially interact with the anticodon
      of tRNAHis. To further explore the effects of the A-loop mutations on virus
      replication, the A-loops complementary to tRNASer or tRNAHis were cloned into the
      wild type genome with the PBS complementary to tRNALys,3. Transfection of
      proviral genomes which contained the wild type PBS and A-loops complementary to
      tRNASer or tRNAHis into 293 T cells did not impact on the production of viruses
      as measured by p24 antigen ELISA. However, viruses with the A-loop complementary
      to tRNAHis had greatly reduced infectivity and replicated poorly in SupT1
      compared to the wild type or viruses with the A-loop complementary to tRNASer.
      CONCLUSION: These studies demonstrate that complementarity of A-loop region with
      the anticodon of tRNAHis has a pronounced effect on the capacity of HIV-1 to
      utilize tRNAHis as the primer for reverse transcription. Complementarity between
      A-loop and anticodon of the tRNA then is important for the selection of the tRNA
      primer used for reverse transcription.

PMID- 17214905
TI  - Zebularine reactivates silenced E-cadherin but unlike 5-Azacytidine does not
      induce switching from latent to lytic Epstein-Barr virus infection in Burkitt's
      lymphoma Akata cells.
AB  - Epigenetic silencing of regulatory genes by aberrant methylation contributes to
      tumorigenesis. DNA methyltransferase inhibitors (DNMTI) represent promising new
      drugs for anti-cancer therapies. The DNMTI 5-Azacytidine is effective against
      myelodysplastic syndrome, but induces switching of latent to lytic Epstein-Barr
      virus (EBV) in vitro and results in EBV DNA demethylation with the potential of
      induction of lytic EBV in vivo. This is of considerable concern given that
      recurrent lytic EBV has been linked with an increased incidence of EBV-associated
      lymphomas. Based on the distinct properties of action we hypothesized that the
      newer DNMTI Zebularine might differ from 5-Azacytidine in its potential to induce
      switching from latent to lytic EBV. Here we show that both 5-Azacytidine and
      Zebularine are able to induce expression of E-cadherin, a cellular gene
      frequently silenced by hypermethylation in cancers, and thus demonstrate that
      both DNMTI are active in our experimental setting consisting of EBV-harboring
      Burkitt's lymphoma Akata cells. Quantification of mRNA expression of EBV genes
      revealed that 5-Azacytidine induces switching from latent to lytic EBV and, in
      addition, that the immediate-early lytic infection progresses to early and late
      lytic infection. Furthermore, 5-Azacytidine induced upregulation of the latent
      EBV genes LMP2A, LMP2B, and EBNA2 in a similar fashion as observed following
      switching of latent to lytic EBV upon cross-linking of the B-cell receptor. In
      striking contrast, Zebularine did not exhibit any effect neither on lytic nor on
      latent EBV gene expression. Thus, Zebularine might be safer than 5-Azacytidine
      for the treatment of cancers in EBV carriers and could also be applied against
      EBV-harboring tumors, since it does not induce switching from latent to lytic EBV
      which may result in secondary EBV-associated malignancies.

PMID- 17214906
TI  - Effectiveness of computer-navigated minimally invasive total hip surgery compared
      to conventional total hip arthroplasty: design of a randomized controlled trial.
AB  - BACKGROUND: Moderate to severe osteoarthrosis is the most common indication for
      Total Hip Arthroplasty (THA). Minimally Invasive Total Hip Surgery (MIS) and
      computer-navigated surgery were introduced several years ago. However, the
      literature lacks well-designed studies that provide evidence of superiority of
      computer-navigated MIS over a conventional THA technique. Hence, the purpose of
      this study is to compare (cost)effectiveness of computer-navigated MIS with a
      conventional technique for THA. It is our hypothesis that computer-navigated MIS
      will lead to a quicker recovery during the early postoperative period (3 months),
      and to an outcome at least as good 6 months postoperatively. We also hypothesize
      that computer-navigated MIS leads to fewer perioperative complications and better
      prosthesis positioning. Furthermore, cost advantages of computer-navigated MIS
      over conventional THA technique are expected. METHODS/DESIGN: A cluster
      randomized controlled trial will be executed. Patients between the ages of 18 and
      75 admitted for primary cementless unilateral THA will be included. Patients will
      be stratified using the Charnley classification. They will be randomly allocated
      to have computer-navigated MIS or conventional THA technique. Measurements take
      place preoperatively, perioperatively, and 6 weeks and 3 and 6 months
      postoperatively. Degree of limping (gait analysis), self-reported functional
      status and health-related quality of life (questionnaires) will be assessed
      preoperatively as well as postoperatively. Perioperative complications will be
      registered. Radiographic evaluation of prosthesis positioning will take place 6
      weeks postoperatively. An evaluation of costs within and outside the healthcare
      sector will focus on differences in costs between computer-navigated MIS and
      conventional THA technique. DISCUSSION: Based on studies performed so far, few
      objective data quantifying the risks and benefits of computer-navigated MIS are
      available. Therefore, this study has been designed to compare (cost)
      effectiveness of computer-navigated MIS with a conventional technique for THA.
      The results of this trial will be presented as soon as they become available.

PMID- 17214907
TI  - Intrathecal colistin for treatment of Pseudomonas aeruginosa ventriculitis:
      report of a case with successful outcome.

PMID- 17214908
TI  - Drotrecogin alfa (activated) in patients with severe sepsis and a high risk of
      death.

PMID- 17214909
TI  - Bench-to-bedside review: Routine postoperative use of the nasogastric tube -
      utility or futility?

PMID- 17214910
TI  - Characterization of the mitochondrial genome of Diphyllobothrium latum (Cestoda:
      Pseudophyllidea) - implications for the phylogeny of eucestodes.
AB  - The complete nucleotide sequence of the mitochondrial genome was determined for
      the fish tapeworm Diphyllobothrium latum. This genome is 13,608 bp in length and
      encodes 12 protein-coding genes (but lacks the atp8), 22 transfer RNA (tRNA) and
      2 ribosomal RNA (rRNA) genes, corresponding to the gene complement found thus far
      in other flatworm mitochondrial (mt) DNAs. The gene arrangement of this
      pseudophyllidean cestode is the same as the 6 cyclophyllidean cestodes
      characterized to date, with only minor variation in structure among these other
      genomes; the relative position of trnS2 and trnL1 is switched in Hymenolepis
      diminuta. Phylogenetic analyses of the concatenated amino acid sequences for 12
      protein-coding genes of all complete cestode mtDNAs confirmed taxonomic and
      previous phylogenetic assessments, with D. latum being a sister taxon to the
      cyclophyllideans. High nodal support and phylogenetic congruence between
      different methods suggest that mt genomes may be of utility in resolving ordinal
      relationships within the cestodes. All species of Diphyllobothrium infect fish
      eating vertebrates, and D. latum commonly infects humans through the ingestion of
      raw, poorly cooked or pickled fish. The complete mitochondrial genome provides a
      wealth of genetic markers which could be useful for identifying different life
      cycle stages and for investigating their population genetics, ecology and
      epidemiology.

PMID- 17214911
TI  - ShAR2beta, a divergent nicotinic acetylcholine receptor subunit from the blood
      fluke Schistosoma.
AB  - Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that
      mediate the fast actions of the neurotransmitter, acetylcholine. Invertebrate
      nAChRs are of interest as they are targets of widely-selling insecticides and
      drugs that control nematode parasites. Here, we report the cloning of ShAR2beta,
      a candidate nAChR subunit from the blood fluke, Schistosoma haematobium, which is
      the third trematode nAChR subunit to be characterized. While ShAR2beta possesses
      key structural features common to all nAChRs, its amino acid sequence shares
      considerably low identity with those of insect, nematode and vertebrate nAChR
      subunits. In particular, the second transmembrane domain of ShAR2beta, which
      lines the ion channel, bears unusual amino acid residues which will likely give
      rise to a receptor with distinct functional properties. Phylogenetic analysis
      shows that ShAR2beta is a divergent nAChR subunit that may define a clade of
      trematode-specific subunits. We discuss our findings in the context of
      potentially exploiting this receptor as a target for controlling schistosome
      parasites.

PMID- 17214912
TI  - Effect of total solids content and temperature on the rheological behaviour of
      reconstituted whole milk concentrates.
AB  - This work investigated the combined effect of solids content, heating and storage
      temperatures on the rheological behaviour of reconstituted whole milk
      concentrates. The powder was reconstituted at 35 degrees C in a custom built
      recombination rig to various total solids content (TS) from 10-48% TS. The
      concentrates were then heated to 45-85 degrees C and stored at the heating
      temperature. The rheological behaviour shifter from Newtonian behaviour (below
      30% TS) to power law (below 40% TS), with the yield stress observed from 40% TS
      upwards and time-dependent behaviour was noticed above 44% TS. Higher heating
      temperatures tend to promote non-Newtonian behaviour at lower solids content. The
      viscosity-solid content curve showed an exponential relationship, while the
      viscosity-temperature curve exhibited a minimum at 65-75 degrees C above 46% TS.
      During age thickening, the yield stress and the consistency coefficient
      increased, while the flow behaviour index decreased with storage time. This
      indicated that the milk concentrates deviated away from Newtonian behaviour
      during age thickening.

PMID- 17214913
TI  - Rheological characterisation of age thickening with special reference to milk
      concentrates.
AB  - Age thickening is a well known phenomenon within the dairy industry, where the
      apparent viscosity of concentrated dairy solutions increases with storage time
      under low shear. The objective of the paper is to develop new tools to analyse
      several aspects of age thickening, including the increases in shear thinning, the
      degree of thixotropy and the rate of structural build up with time, as well as
      irreversible structural changes and gelation. The build up of the dispersed phase
      structure during storage, was captured by a snap shot technique, where
      concentrated milk samples were stored, and aliquots were taken at periodic
      intervals and subjected to shear sweep tests to collect flow curves. Rheological
      modelling using the Herschel-Bulkley model showed an increase in yield stress and
      consistency, indicating a build up in structure during age thickening. The trend
      in apparent viscosity with storage time showed two-phases, a slow and steady
      increase followed by a sharp rise, which could be used to identify the onset of
      firm gelation. The extrapolated viscosity at infinite shear rate increased with
      storage time, indicating the build up in irreversible structural components
      during age thickening.

PMID- 17214914
TI  - The identification of a genetically unique piroplasma in North American river
      otters (Lontra canadensis).
AB  - During a routine health check of a wild-caught North American river otter (Lontra
      canadensis) small piroplasms were noted within erythrocytes. Analyses of the 18S
      ribosomal ribonucleic acid (rRNA) gene sequences determined that this was a
      genetically unique organism most closely related to Babesia microti-like
      parasites found in other small carnivores. Subsequently 39 wild-trapped North
      American river otters from North Carolina were tested for the presence of
      piroplasma deoxyribonucleic acid (DNA) via polymerase chain reaction and
      piroplasma DNA was detected in 82% (32/39) of these samples. Sequencing of
      partial 18S rRNA genes from selected cases determined that they were identical to
      the sentinel case. This report documents the existence of a genetically unique
      piroplasma in North American river otters and indicates that the prevalence of
      piroplasma in North Carolina otters is quite high. The pathogenic potential of
      this organism for otters or other species remains unknown.

PMID- 17214916
TI  - Interventions for low back pain: what does the evidence tell us.
AB  - Although interventional therapy for chronic spinal pain continues to be popular
      among patients and providers, the scientific evidence supporting these techniques
      has lagged behind their presence in the market. This article collates both
      classic and more recent experimental results involved in the interventional
      assessment and treatment of chronic spinal pain, and presents key findings for
      physicians. Although much of the body of evidence is either unsupportive or
      inconclusive, there are some definitive findings involving each technique that
      can help shape rational practice. As interventional pain medicine seeks to become
      a more validated specialty, introspection and advancing science will be key to
      this development.

PMID- 17214915
TI  - Chronic pain after surgery: what can we do to prevent it.
AB  - The development of chronic pain after surgery is not an uncommon event. Despite
      increased attention devoted to this topic in the recent medical literature,
      little is known about the underlying mechanisms, natural history, and response to
      therapy of each syndrome. Central nervous system plasticity that occurs in
      response to tissue injury may contribute to the development of persistent
      postsurgical pain. As evidence continues to accumulate concerning the role of
      central sensitization in the prolongation of postoperative pain, many researchers
      have focused on methods to prevent central neuroplastic changes from occurring
      through the use of preemptive or preventative analgesic techniques. Effective
      preventative analgesic techniques may be useful in reducing not only acute pain
      but also chronic postsurgical pain and disability. This review examines the
      efficacy of using a variety of analgesic techniques aimed at preventing or
      reducing chronic pain after surgery. Specific chronic postsurgical pain syndromes
      evaluated include complex regional pain syndrome, phantom limb pain, chronic
      donor site pain, post-thoracotomy pain syndrome, and postmastectomy pain
      syndrome.

PMID- 17214917
TI  - Intravenous lidocaine for neuropathic pain: diagnostic utility and therapeutic
      efficacy.
AB  - Lidocaine is a use-dependent sodium channel blocker that produces analgesia when
      administered intravenously to patients with neuropathic pain. This article
      reviews the role and limitations of intravenous lidocaine infusions for
      neuropathic pain. Lidocaine infusions rarely provide relief that persists
      significantly beyond the duration of the infusion. Diagnostically, systemic
      lidocaine may help establish the presence of neuropathic pain and the
      responsivity to oral sodium channel blockade. However, the data supporting
      diagnostic infusions remain sparse. Therapeutically, infusions should generally
      be restricted to patients with neuropathic pain who are unable to take oral
      medication.

PMID- 17214918
TI  - Ultrasound-guided peripheral nerve blockade.
AB  - Peripheral nerve blockade (PNB) for orthopedic surgery is usually performed
      without visual guidance, relying mainly on surface anatomic landmarks and
      electrical stimulation to localize nerves. Moreover, multiple trial and error
      attempts to place a needle can frustrate the operator, cause unwarranted pain to
      the patient, and waste valuable time in the operating room. Inaccurate needle
      placement and spread of local anesthetic account for most PNB failures, whereas
      "trial and error" needle manipulations for nerve localization can cause
      complications. The recent application of ultrasound (US) to PNB affords real-time
      imaging of the target nerve, needle, and surrounding vasculature, such that
      needle proximity to the nerve is ensured and vascular puncture avoided. This
      article reviews the advantages, principles, and techniques of US for the most
      common types of PNB.

PMID- 17214919
TI  - Extended-duration agents for perioperative pain management.
AB  - Perioperative pain management has drastically evolved over the years to satisfy
      current unmet needs. Intermittent delivery of drugs has been replaced by
      continuous delivery systems involving oral, neuraxial, and peripheral nerve block
      routes of administration. One current standard of perioperative pain management
      is an epidural injection of an opioid such as morphine, fentanyl, or
      hydromorphone, with or without the addition of a local anesthetic, such as
      bupivacaine. Although this method is extremely effective in controlling pain
      during the most critical 48-hour period postoperatively, it also has its
      disadvantages. Risks associated with indwelling epidural catheters include
      infection, adverse effects, and spinal hematoma. The development of extended- and
      controlled-release drug delivery systems has revolutionized perioperative pain
      management. This class of drugs comprises MS Contin (Purdue Pharma LP, Stamford,
      CT), OxyContin (Purdue Pharma LP), Opana ER (Endo Pharmaceuticals, Chadds Ford,
      PA), and DepoDur (Endo Pharmaceuticals). There are also phase II trials in
      progress examining controlled-release formulations of local anesthetics. This
      review discusses extended- and controlled-release agents administered
      perioperatively.

PMID- 17214920
TI  - Pharmacologic therapies for complex regional pain syndrome.
AB  - Complex regional pain syndrome (CRPS) remains a challenging condition to diagnose
      and treat. There are few large-scale, randomized trials of pharmacologic agents,
      and most published studies are small, uncontrolled, or presented only in abstract
      form at meetings. The most commonly used agents, such as anticonvulsants,
      antidepressants, and opiates, have been found to be useful for other neuropathic
      pain conditions in large-scale trials but have not been adequately studied in
      CRPS. Systemic steroids delivered by multiple routes continue to be used, with
      some good evidence for short-term administration. N-methyl-D-aspartate
      antagonists have recently gained in popularity, without evidence from well
      controlled trials. Bisphosphonates have been well studied and offer promise. In
      addition, there has been interest in thalidomide; however, we are still awaiting
      well-controlled trials. This article presents an overview of the available data
      regarding pharmacologic therapies for CRPS. These agents should be used in
      conjunction with a comprehensive interdisciplinary approach aimed at functional
      restoration and improved quality of life.

PMID- 17214921
TI  - Diagnostic testing for chronic daily headache.
AB  - Primary chronic headaches of long duration include chronic migraine, chronic
      tension-type headache, new daily persistent headache, and hemicrania continua.
      This article reviews the utility of neuroimaging and other testing for diagnosis
      of these headaches. The presentation and diagnosis of the many secondary
      headaches that can mimic primary headache types are also discussed, including
      arteriovenous malformations, spontaneous intracranial hypotension, neoplasms,
      pseudotumor cerebri, cervical artery dissections, cerebral venous thrombosis,
      Chiari I malformation, and temporal arteritis. Although the yield of diagnostic
      testing is low, serious pathology as a cause of chronic headaches can be easily
      overlooked.

PMID- 17214922
TI  - Is Chiari type I malformation a reason for chronic daily headache.
AB  - This article briefly reviews the spectrum of headaches associated with Chiari
      type I malformation and specifically analyzes current data on the possibility of
      this malformation as an etiology for some cases of chronic daily headache (CDH).
      Chiari type I malformation is definitely associated with cough headache and not
      with primary episodic headaches, with the rare exception of basilar migraine-like
      cases. With regard to CDH, there is no clear evidence supporting an association
      with this malformation. An MRI study would be justified only in patients showing
      either a Valsalva-aggravating component or cervicogenic features. Hydrocephalus
      and low intracranial pressure syndrome should be ruled out in patients showing
      tonsillar herniation in an MRI study and consulting due to daily headache.

PMID- 17214923
TI  - Spontaneous intracranial hypotension.
AB  - Spontaneous intracranial hypotension (SIH) is caused by leakage of cerebrospinal
      fluid (CSF), with resultant CSF hypovolemia and intracranial hypotension.
      Although in some patients SIH may be preceded by minor trauma, it often occurs in
      the absence of any identifiable initiating event. Orthostatic headache is the
      primary clinical manifestation, usually accompanied by one or more other symptoms
      of SIH. Diagnosis can be reached by a combination of imaging studies, which may
      include MRI with gadolinium, nuclear cisternography, and myelography. Treatment
      ranges from conservative management, such as bed rest and hydration, to invasive
      procedures, such as lumbar puncture with autologous blood patch, CT-guided fibrin
      glue injection at the site of the leak, and open surgical intervention. Outcomes
      vary from complete resolution of CSF leak with alleviation of symptoms to
      continued and/or recurrent leaks with chronic unremitting symptomatology.

PMID- 17214924
TI  - Idiopathic intracranial hypertension.
AB  - Idiopathic intracranial hypertension is a secondary headache disorder
      characterized by headaches and visual symptoms. It most frequently occurs in
      obese women of childbearing age. However, many secondary causes exist, and it may
      affect children, men, and slim individuals. Prompt recognition, evaluation, and
      treatment are needed to prevent permanent visual loss.

PMID- 17214925
TI  - Trigeminal neuralgia.
AB  - The paroxysmal facial pain of trigeminal neuralgia is notoriously severe. Recent
      advances in medical science are achieving significant strides toward alleviating
      this incapacitating condition. High-resolution neuroimaging techniques are
      rendering detailed views of underlying neurovascular relationships. Newer
      antiepileptic medications and novel therapies are proving helpful in treating
      pain resistant to carbamazepine. Further developments also in targeted
      neurosurgical and radiosurgical techniques are providing pain relief within
      increasingly wider margins of safety. Much has been accomplished, yet much
      remains to be done.

PMID- 17214927
TI  - [Administration and quality control of large-scale clinical trials of traditional
      Chinese medicine].
AB  - Abstract: Large-scale clinical trial is an important measure of clinical
      evaluation on drugs. This paper introduces the concept and features of large
      scale clinical trial, the possibility and necessity of large-scale clinical trial
      of traditional Chinese medicine, as well as its administration and quality
      control, with Myocardial Infarction Secondary Prevention Study in Traditional
      Chinese Medicine (MISPS-TCM), a National Program Subject, as an example.

PMID- 17214928
TI  - [An optimized 3-step strategy for preventing and treating post-operation relapse
      and metastasis of malignant tumors with traditional Chinese medicine].
AB  - Abstract: Relapse and metastasis are the main causes responsible for failure of
      surgical operation in treating malignant tumors. This article introduces the
      present development in post-operation treatment of lung cancer, liver cancer and
      stomach cancer, showing that the synthetic treatment by stages combined with
      traditional Chinese medicine is the important way to prevent and treat the post
      operation relapse and metastasis of tumors, and suggesting the optimized method
      for treatment.

PMID- 17214926
TI  - Temporomandibular disorders and other causes of facial pain.
AB  - Temporomandibular disorders and facial pain cause significant discomfort and
      disability for affected patients. Understanding the clinical presentation,
      pathogenesis, and therapy is essential in helping patients who have these
      problems. This article critically reviews these aspects, with an emphasis on
      their relationship to headache.

PMID- 17214929
TI  - [Methods of selecting outcome variables for clinical intervention].
AB  - Abstract: There are two stages for selecting the clinical intervention outcome
      variables. One is crude collection and the other is precise collection. The
      selection methods include brainstorming method, Delphi method, Gordon method,
      systematic review, systematic analysis method, mathematic model method and so on.
      Each method has some advantages or disadvantages. When selecting the clinical
      intervention outcome variables, researchers should make sure the research aim,
      the representative and the sensitivity of the variables, and select all kinds of
      recommended methods comprehensively, then decide which method should be used.

PMID- 17214930
TI  - [Construction of a therapeutic effect evaluation system for patients with primary
      liver cancer based on syndrome differentiation in traditional Chinese medicine].
AB  - OBJECTIVE: To construct a system of therapeutic effect evaluation for patients
      with primary liver cancer according to the theory of syndrome differentiation in
      traditional Chinese medicine (TCM), and to examine its reliability. METHODS:
      Analytic hierarchy process and 100 mm surveyor's rod method were applied to
      obtain bottom layer and top level syndromes, which were used to construct the
      method of therapeutic effect evaluation, and its reliability was verified in
      clinical practice by comparing with some evaluation criteria in Western medicine,
      such as cancer severity scale; Karnofsky performance scale; Child-Pugh
      classification, cancer staging classification, and quality of life scale, etc.
      RESULTS: A system of therapeutic effect evaluation was constructed, and it could
      reflect the progress of tumor, changes of hepatic function and constitution. The
      evaluation scores acquired from the system were highly associated with the
      quality of life of the patients. CONCLUSION: The system of therapeutic effect
      evaluation can reflect the severity of disease and the characteristics of TCM
      treatment.

PMID- 17214931
TI  - [A randomized controlled trial of Yiqi Pingchuan Granule in treating acute attack
      of bronchial spasm due to asthma of qi deficiency and cold syndrome].
AB  - OBJECTIVE: To evaluate the safety and efficacy of Yiqi Pingchuan Granule in
      treating acute attack of asthma due to qi deficiency and cold syndrome. METHODS:
      A randomized controlled trial was conducted. A total of 80 patients with an acute
      attack of asthma were included. They were allocated into two groups randomly in a
      ratio of three to one. Sixty patients in the treatment group received Yiqi
      Pingchuan Granule and 20 patients in the control group received Ruyi Dingchuan
      Pill. Patients in both groups were treated for 7 days. RESULTS: There were no
      significant differences in traditional Chinese medicine syndrome, clinical
      symptoms and lung function between the two groups (P>0.05). After treatment, the
      forced expiratory volume in 1 second was increased in the treatment group
      (P<0.05), and the peak expiratory flow was accelerated in the control group
      (P<0.05). No significant side effects were noted in both groups. CONCLUSION: Yiqi
      Pingchuan Granule is safe and effective in treating acute attack of asthma due to
      qi deficiency and cold syndrome.

PMID- 17214932
TI  - [Effects of Salvia miltiorrhiza on serum levels of inflammatory cytokines in
      patients with severe acute pancreatitis].
AB  - OBJECTIVE: To study the effects of Salvia miltiorrhiza on serum levels of
      cytokines including interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis
      factor-alpha (TNF-alpha) in patients with severe acute pancreatitis (SAP).
      METHODS: Thirty-six SAP patients were randomly divided into Salvia miltiorrhiza
      treated group and non-Salvia miltiorrhiza-treated group with eighteen patients in
      each group. Fourteen age-matched healthy volunteers were assigned to control
      group. Serum levels of IL-6, IL-8, and TNF-alpha were tested within 24 hours of
      admission and 7 days after admission. RESULTS: Compared with those of the healthy
      volunteers, serum levels of the three cytokines of the SAP patients were
      significantly elevated (P<0.05). Serum levels of the three cytokines were
      significantly decreased in both Salvia miltiorrhiza-treated group and non-Salvia
      miltiorrhiza-treated group after 7-day treatment (P<0.05). The declining of the
      serum levels of the three cytokines in Salvia miltiorrhiza-treated group was more
      obvious than that in non-Salvia miltiorrhiza-treated group. CONCLUSION: Salvia
      miltiorrhiza can treat SAP patients by reducing the serum levels of IL-6, IL-8,
      and TNF-alpha.

PMID- 17214933
TI  - [Predictive role of diagnostic information in treatment efficacy of rheumatoid
      arthritis based on neural network model analysis].
AB  - OBJECTIVE: To analyze the indications of the therapies for rheumatoid arthritis
      (RA) with neural network model analysis. METHODS: Three hundred and ninety-seven
      patients were included in the clinical trial from 9 clinical centers. They were
      randomly divided into Western medicine (WM) treated group, 194 cases; and
      traditional Chinese herbal medicine (CM) treated group, 203 cases. A complete
      physical examination and 18 common clinical manifestations were prepared before
      the randomization and after the treatment. The WM therapy included voltaren
      extended action tablet, methotrexate and sulfasalazine. The CM therapy included
      Glucosidorum Tripterygii Totorum Tablet and syndrome differentiation treatment.
      The American College of Rheumatology 20 (ACR20) was taken as efficacy evaluation.
      All data were analyzed on SAS 8.2 statistical package. The relationships between
      each variable and efficacy were analyzed, and the variables with P<0.2 were
      included for the data mining analysis with neural network model. All data were
      classified into training set (75%) and verification set (25%) for further
      verification on the data-mining model. RESULTS: Eighteen variables in CM and 24
      variables in WM were included in the data-mining model. In CM, morning stiffness,
      swollen joint number, peripheral immunoglobulin M (IgM) level, tenderness joint
      number, tenderness, rheumatoid factor (RF), C-reactive protein (CRP) and joint
      pain were positively related to the efficacy, and disease duration and more
      urination at night negatively related to the efficacy. In WM, erythrocyte
      sedimentation rate (ESR), weak waist, white fur in tongue, joint pain, joint
      stiffness and swollen joint were positively related to the efficacy, and yellow
      fur in tongue, red tongue, white blood negatively related to the efficacy. In the
      analysis with the neural network model in the patients of verification set, the
      predictive response rates of 20% patients would be 100% and 90% in the treatment
      with CM and WM, respectively. CONCLUSION: Neural network model analysis, based on
      the full clinical trial data with collection of both traditional Chinese medicine
      and modern medicine diagnostic information, shows a good predictive role for the
      information in the efficacy in rheumatoid arthritis.

PMID- 17214934
TI  - [A rabbit model of cervical spondylosis established by stimulation of wind, cold
      and dampness].
AB  - OBJECTIVE: To make an animal model of cervical spondylosis (arthralgia syndrome
      type) with stimulation of wind, cold, and dampness. METHODS: Twenty-four 8 months
      old male New Zealand white rabbits were randomly allocated into four groups:
      normal control group, light stimulation group, moderate stimulation group and
      severe stimulation group. The wind speed was 10.8-13.8 m/s, the temperature was
      (5+/-0.5)degrees centigrade, and the humidity was 100%. The rabbits of light,
      moderate, and severe stimulation groups were kept in the above-mentioned
      environments for 4 hours everyday, and for a total of 32, 64, and 128 hours,
      respectively. The intervertebral discs were stained with HE method, and observed
      with a light microscope. Prostaglandin E(2) (PGE(2)), 6-ketone-prostaglandin
      F1alpha (6-K-PGF(1alpha)) and thromboxane B(2) (TXB(2)) contents were measured by
      ELISA. Fas and Bcl-2 expressions were examined by immunohistochemical avidin
      biotin peroxidose complex technique. Interleukin-1beta (IL-1beta), tumor necrosis
      factor alpha (TNF-alpha), and transforming growth factor beta (TGF-beta) mRNA
      expressions were examined by reverse transcription-polymerase chain reaction.
      RESULTS: The nucleus pulposus of rabbits in the light and moderate stimulation
      groups shrunken, and in the severe stimulation group, the anulus fibrosus loosed
      or ruptured, and the cartilage end-plate became proliferated. Compared with
      rabbits in the normal control group, the PGE(2) content rose in the light
      stimulation group, the contents of PGE(2), 6-K-PGF(1alpha), and TXB(2) increased,
      the expressions of IL-1beta and TNF-alpha mRNAs and Fas were up-regulated, and
      the expressions of TGF-beta mRNA and Bcl-2 were down-regulated in the moderate
      and severe stimulation groups. The expression of Fas was up-regulated mostly and
      Bcl-2 was down-regulated mostly in the severe group. CONCLUSION: Moderate and
      severe stimulations of wind, cold and dampness can lead to degeneration of
      cervical intervertebral discs of rabbits. The model corresponds to the theory of
      traditional Chinese medicine about arthralgia syndrome caused by wind, cold and
      dampness.

PMID- 17214935
TI  - [Effects of water extractives of a qi and blood regulating prescription on early
      atherosclerosis of apolipoprotein E-deficient mice].
AB  - OBJECTIVE: To investigate whether the water extractives of regulating qi and
      blood prescription (WQBP) had effects on early atherosclerosis of apolipoprotein
      E-deficient mice (ApoE-mice) at the age of 19 weeks or not, and to explore the
      possible mechanisms. METHODS: Forty ApoE-mice, six weeks of age, were given high
      fat diet and randomly divided into four groups: high-dose WQBP-treated group (360
      mg/kg), low-dose WQBP-treated group (72 mg/kg), simvastatin-treated group (25
      mg/kg) and untreated group, with ten mice in each group. Meanwhile, ten C57BL/6
      mice of same genetic background were allocated to normal control group. Mice in
      the high- and low-dose WQBP-treated groups and simvastatin-treated group were
      administered with corresponding drugs from the 15 to 19 weeks. Mice in the
      untreated and normal control groups were administered with isovolumic water.
      Sacrificed at 19 weeks, the level of blood-lipid, the plaque construction, plaque
      integral, and the contents of plaque macrophages and vessel smooth muscle cells
      of the mice were analyzed by immunohistochemical method and a computer picture
      processing system. RESULTS: Compared to the untreated group, high-dose WQBP group
      could obviously decrease the level of low-density lipoprotein cholesterol (LDL
      C). Simvastatin group could decrease the levels of LDL-C and total cholesterol
      (TC) (P<0.01). In high-dose WQBP-treated group and simvastatin-treated group, the
      thickness of fiber cap and the quantities of vessel smooth muscle cells increased
      (P<0.05), the quantities of plaque macrophages and the ratio of lipid and plaque
      reduced (P<0.01). CONCLUSION: WQBP and simvastatin can interfere in early
      atherosclerosis of ApoE-mice, attenuate and stabilize plaque in some extent. The
      mechanisms may include adjusting blood lipid, decreasing macrophage number and
      increasing the quantities of vessel smooth muscle cells.

PMID- 17214936
TI  - [Effects of Gymnadenia conopsea alcohol extract on collagen synthesis in rat
      lungs exposed to silica and its mechanism of antioxidative stress].
AB  - OBJECTIVE: To explore the effects of Gymnadenia conopsea alcohol extract (GcAE)
      on the collagen synthesis in rat lungs exposed to silica and the influence on
      antioxidase activities, level of lipid peroxidation (LPO). METHODS: One hundred
      and twenty rats were randomly divided into control group, silica group, and GcAE
      treated group. Silicotic animal models were established by direct tracheal
      instillation of silica into rat lungs surgically. From the second day of model
      establishment, rats in GcAE-treated group were orally given GcAE [8 g/(kg x d)
      corresponding to raw herb]. At 7, 14, 21, 28 and 60 days after establishment of
      the animal model, eight rats in each group were sacrificed, and samples were
      collected. The malondialdehyde (MDA) content, superoxide dismutase (SOD) and
      glutathione peroxidase (GPx) activities in plasma were assayed by a
      spectrophotometer. Types I and III collagen were detected by Sirius red
      polarization and microscopy, and measuered by Image-Pro Plus Version 4.5 for
      Windows software. RESULTS: GcAE could reduce the lung/body weight ratio of rats
      exposed to silica, the synthesis of types I and III collagen of the lungs and the
      level of lipid peroxidation, increase the activities of SOD and GPx. CONCLUSION:
      GcAE can ameliorate the silica-induced pulmonary fibrosis by increasing the
      activities of antioxidase and alleviating the damage of lipid peroxidation to the
      lungs.

PMID- 17214937
TI  - [Inhibitory effects of 11 coumarin compounds against growth of human bladder
      carcinoma cell line E-J in vitro].
AB  - OBJECTIVE: To screen antitumor active compounds, drug-like or leading compounds
      from Chinese traditional and herbal drugs. METHODS: Eleven coumarin compounds
      isolated from the Chinese traditional and herbal drugs were studied for their
      antitumor activities in vitro by determining the inhibition rates against growth
      of human bladder carcinoma cell line E-J. RESULTS: It showed that umbelliferone,
      scoparone, demethylfuropinarine, isopimpinellin, forbesoside, columbianadin,
      decursin and glycycoumarin inhibited the growth of human bladder carcinoma cell
      line E-J in vitro and their activities showed a concentration-effect
      relationship. The inhibitory effects of forbesoside, columbianadin, decursin and
      umbelliferone, with IC50 values of 7.50x10(-7), 2.30x10(-6), 6.00x10(-6) and
      1.30x10(-6) mol/L, respectively, were stronger than those of the other tested
      compounds. However, xanthotoxin, esculin and sphondin did not inhibit the growth
      of human bladder carcinoma cell line E-J in this assay condition. CONCLUSION:
      These findings indicate that forbesoside, columbianadin, esculin, decursin and
      umbelliferone would be effective or regarded as potent drug-like or leading
      compounds against human bladder carcinoma.

PMID- 17214938
TI  - [Effect and mechanism of salvianolic acid B in attenuating elevated portal
      pressure in a rat model of portal hypertension induced by endothelin-1].
AB  - OBJECTIVE: To investigate the effects of salvianolic acid B (SA-B) on portal
      hypertension induced by endothelin-1 in rats. METHODS: Twenty-eight Sprague
      Dawley rats were randomly divided into four groups: ET-1 group, ET-1+SA-B group,
      ET-1+ET(A)R blocker (BQ-123) group and ET-1+ET(B)R blocker (BQ-788) group. The
      rats of ET-1+SA-B group underwent intragastrical administration of salvianolic
      acid B for five days before ET-1 injection, while in three other groups' drinking
      water was given. In BQ-123 group or BQ-788 group, an intravenous injection of BQ
      123 or BQ-788 via femoral vein was administered 30 minutes prior to ET-1
      injection. Then changes of portal pressure, cervical artery pressure and heart
      rate were monitored continuously. RESULTS: After ET-1 injection, the portal
      pressure of all rats in the ET-1 group increased significantly, while slightly in
      groups that pretreated with SA-B, BQ-123 or BQ-788. CONCLUSION: SA-B can
      attenuate the elevated portal pressure induced by ET-1 with effect similar to ETR
      blocker.

PMID- 17214939
TI  - [Effects of inactivated rabbit serum containing compound realgar and natural
      indigo tablet on cell line NB4].
AB  - OBJECTIVE: To explore the effects of inactivated rabbit serum containing compound
      realgar and natural indigo tablet (CRNIT) on cell line NB(4). METHODS: The
      experimental rabbits were taken as the provider of the animal serum, and the
      serum was inactivated before the experiment. The serum was divided into two
      groups based on whether the rabbits were given CRNIT. The concentration of
      arsenic in the rabbit's serum was detected by AFS-230a double path atom
      fluorescence photometer. The inhibition rates and apoptosis rates were regarded
      as the observational indexes. RESULTS: The concentration of arsenic in the
      inactivated rabbit serum containing and not containing the drug were (0.010 0+/
      0.001 0) mg/L and (0.110 0+/-0.006 4) mg/L respectively, and the difference had
      statistical significance (P<0.01). The two groups of serum all had inhibitory
      effect on the growth of NB(4) cells depending on the drug concentration and
      effect time. And there were significant differences among the groups. The two
      groups of serum all induced the apoptosis of NB(4) with positive relations with
      the concentration and effect time. And there were significant differences among
      the groups. CONCLUSIONS: The rabbit serum containing CRNIT can obviously restrain
      the growth of NB(4) cells and the inhibitory effect depends on the concentration
      and effect time. And the rabbit serum containing CRNIT can also induce the
      apoptosis of NB(4) cell line and the apoptosis rates depend on the concentration
      and effect time.

PMID- 17214940
TI  - [An experimental serum pharmacological study on an application method in
      traditional Chinese medicine for treatment and prevention of asthma].
AB  - OBJECTIVE: To study the mechanism of herbal application along meridians for
      treatment and prevention of asthma by using serum pharmacological test to observe
      the effects of serum containing herbs against the constriction of tracheal spiral
      strips induced by acetylcholine chloride (Ach). METHODS: Guinea pigs were
      randomly divided into normal control group, normal saline (NS) application group,
      aminophylline application group, aminophylline injection group, 1-day herb
      application group, 7-day herb application group and 14-day herb application
      group. Asthma was induced by Hutson's method in guinea pigs except the normal
      control group. Guinea pigs in herb application groups were treated by external
      application of a compound herbal medicine 60 min once every day. Guinea pigs in
      NS application group were treated by external application of NS. Guinea pigs in
      the two aminophylline-treated groups were treated by external application and
      intraperitoneal injection of aminophylline at a dose of 400 mg/kg, respectively.
      The guinea pigs were killed and the sera were obtained after 1-day, 7-day and 14
      day treatment in the three herb application groups, 7-day treatment in the NS
      application group, the aminophylline application and injection groups,
      respectively. Serum pharmacological method was used to do the experiment, the
      effects of different sera on the constriction of tracheal strips were observed,
      and the constriction rates were calculated. RESULT: The serum containing herbs
      had an effect in reducing the constriction of tracheal spiral strips induced by
      Ach, and the effect was similar to that of the serum obtained from the
      aminophylline injection group. The constriction rate of the tracheal spiral
      strips was decreased when herbal application treatment was prolonged within a
      period of time, and it became stable when herbal application treatment was
      between 7-14 days. The constriction of tracheal spiral strips induced by Ach
      could be reduced remarkably when it was previously treated by serum containing
      herbs. CONCLUSION: The anti-acetylcholine function with a time-dependent effect
      is one of the mechanisms of herbal application treatment along meridians for
      asthma, and furthermore, herbal application treatment along meridians might be
      useful for preventing asthma.

PMID- 17214941
TI  - [Comparison of acute toxicity of two preparations of norcantharidin in mice].
AB  - OBJECTIVE: To compare the acute toxicity of common injection and sustained
      release preparation of norcantharidin for mice so as to identify the attenuation
      of the sustained-release preparation of norcantharidin. METHODS: The poloxamer
      407 was used as a sustained-release vehicle for topical administration of
      norcantharidin, and the acute toxicity of mice treated with common injection and
      sustained-release preparation of norcantharidin was observed. The median lethal
      dose (LD(50)) was calculated by Bliss software. RESULTS: The symptoms of mice
      were similar between the two groups, but the appearance of symptoms in
      norcantharidin/poloxamer 407 group was 4 hours later than that in norcantharidin
      group. The LD(50) of norcantharidin administered through vein injection was 12.6
      mg/kg. The LD(50) of norcantharidin/poloxamer 407 administered through
      intraperitoneal injection, intrahepatic injection and intramuscular injection
      were 19.9, 19.1 and 20.9 mg/kg, respectively, and the LD(50) of the common
      preparation were 13.0, 13.1 and 15.1 mg/kg, respectively. CONCLUSION: The
      norcantharidin/poloxamer 407 is less toxic than the equivalent dose of
      norcantharidin, mainly because norcantharidin/poloxamer 407 may release
      norcantharidin sustainedly, thus reducing norcantharidin concentration in blood.

PMID- 17214942
TI  - [Diuretic effect of injecting furosemide into low hydraulic resistance point
      Shuifen along the conception meridian in pigs with acute edema].
AB  - OBJECTIVE: To observe whether injection of medicine into low hydraulic resistance
      point along meridian brings about higher medicinal effect and to explore the
      efficacy of the theory that meridians are made up of channels featuring low
      hydraulic resistance by observing the diuretic effect of injecting furosemide or
      saline into the low hydraulic resistance point Shuifen (CV 9), vein and Zusanli
      (St 36) respectively. METHODS: Acute edema was induced in pigs by rapid
      intravenous injection of 2 000 ml normal saline. The pigs were divided into four
      groups: Shuifen (CV 9) injection of half dose furosemide group (SFF group),
      intravenous injection of full dose furosemide group (VF group), Zusanli (St 36)
      injection of full dose furosemide group (ZSLF group), and Shuifen (CV 9)
      injection of half dose normal saline group (SFS group). The accumulated urine
      quantity and the urine quantity generated in every 15-minute period were measured
      in each group respectively, every 15 minutes after injection, and the measurement
      lasted for two hours at one experiment. Each group involved eight times of
      experiments with one pig used for one experiment, which means the whole
      observation involved 32 times of experiments. RESULTS: The accumulated urine
      quantities observed in both SFF group and VF group were higher than those in the
      ZSLF group and the SFS group all through the measurement, showing significant
      differences during the period from the 15th minute to the 45th minute (P<0.05).
      But no significant difference was observed between the SFF group and the VF group
      during the whole 2-hour measurement (P>0.05). Analysis of urine quantity
      generated in every 15-minute period showed that diuretic effect climaxed during
      the 15th minute to the 30th minute in both SFF group and VF group. By contrast,
      ZSLF group reached diuresis climax during the 45th minute to 60th minute and no
      diuresis climax was observed in the SFS group all through the measurement.
      CONCLUSION: Injection of medicine into low hydraulic resistance point along
      meridian generates faster and more powerful medicinal potency, and this is likely
      to be applied to clinical practice. The theory that meridians are channels
      featuring low hydraulic resistance is important to the elucidation of meridians.

PMID- 17214943
TI  - [Experience in syndrome differentiation and treatment of palpitation].

PMID- 17214944
TI  - [Progress of treatment for bladder cancer].

PMID- 17214945
TI  - [Progress in research of traditional Chinese medicine in inducing differentiation
      of human hepatoma cells].

PMID- 17214946
TI  - [How to make out misuse of statistics in manuscripts or papers quickly and
      accurately].

PMID- 17214947
TI  - [Analysis of variance of repeated data measured by water maze with SPSS].
AB  - OBJECTIVE: To introduce the method of analyzing repeated data measured by water
      maze with SPSS 11.0, and offer a reference statistical method to clinical and
      basic medicine researchers who take the design of repeated measures. METHODS:
      Using repeated measures and multivariate analysis of variance (ANOVA) process of
      the general linear model in SPSS and giving comparison among different groups and
      different measure time pairwise. RESULTS: Firstly, Mauchly's test of sphericity
      should be used to judge whether there were relations among the repeatedly
      measured data. If any (P<or=0.05), multivariate ANOVA should be taken next, or
      Greenhouse-Geisser corrected results should be taken. Treated effect could be
      evaluated by estimating between-subject variance. Repeated measurement effect or
      its interactive effect with treated group could be evaluated by estimating within
      subject variance. The method of Bonferroni should be used to do pairwise
      comparisons of the repeatedly measured data in different measurement time of each
      treated group. With multivariate ANOVA, data in different treated group of each
      measurement time could be compared pairwise. CONCLUSION: The repeated measures
      process of the general linear model is suitable for variance analysis of
      repeatedly measured data. SPSS statistical package is available to fulfil this
      process.

PMID- 17214948
TI  - [Understanding the nature of translation through a comparison between the English
      version and the original Chinese of Forward to English Translation of Yellow
      Emperor's Canon of Medicine].

PMID- 17214949
TI  - Corporate financial decision-makers' perceptions of workplace safety.
AB  - This study, through a random national survey, explored how senior financial
      executives or managers (those who determined high-level budget, resource
      allocation, and corporate priorities) of medium-to-large companies perceive
      important workplace safety issues. The three top-rated safety priorities in
      resource allocation reported by the participants (overexertion, repetitive
      motion, and bodily reaction) were consistent with the top three perceived causes
      of workers' compensation losses. The greatest single safety concerns reported
      were overexertion, repetitive motion, highway accidents, falling on the same
      level and bodily reaction. A majority of participants believed that the indirect
      costs associated with workplace injury were higher than the direct costs. Our
      participants believed that money spent improving workplace safety would have
      significant returns. The perceived top benefits of an effective workplace safety
      program were increased productivity, reduced cost, retention, and increased
      satisfaction among employees. The perceived most important safety modification
      was safety training. The top reasons senior financial executives gave for
      believing their safety programs were better than those at other companies were
      that their companies paid more attention to and emphasized safety, they had
      better classes and training focused on safety, and they had teams/individuals
      focused specifically on safety.

PMID- 17214951
TI  - Honoring Professor Nissim Garti.

PMID- 17214950
TI  - Trypanosoma cruzi strains, Tulahuen 2 and Y, besides the difference in resistance
      to oxidative stress, display differential glucose-6-phosphate and 6
      phosphogluconate dehydrogenases activities.
AB  - The drugs currently available for Chagas'disease treatment are unsatisfactory due
      to limited efficacy and toxic side effects, making the search for more specific
      pharmacological agents a priority. The components of the Trypanosoma cruzi
      trypanothione-dependent antioxidant system have been pointed out as potential
      chemotherapeutic targets for the development of more specific drugs. To work
      properly, this system must have a current supply of NADPH, provided by glucose-6
      phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD). Here,
      we compare two T. cruzi strains, Tulahuen 2 and Y, regarding growth rate,
      cytosolic tryparedoxin peroxidase (TcCPX) concentration and pentose phosphate
      pathway dehydrogenases activities. Tulahuen 2 cells show higher values as
      compared to the Y strain when the following parameters are compared: TcCPX
      concentration, resistance to H2O2, growth index and G6PD activity. Different
      patterns of G6PD and 6PGD activities were observed among strains along the growth
      curve and when cells were challenged with H2O2. These data reinforce the
      heterogeneity within T. cruzi populations and also the importance of G6PD in
      protecting the parasite against reactive oxygen species.

PMID- 17214952
TI  - Use of mixture distributions to deconvolute the behavior of "hits" and controls
      in high-throughput screening data.
AB  - The stochastic nature of high-throughput screening (HTS) data indicates that
      information may be gleaned by applying statistical methods to HTS data. A
      foundation of parametric statistics is the study and elucidation of population
      distributions, which can be modeled using modern spreadsheet software. The
      methods and results described here use fundamental concepts of statistical
      population distributions analyzed using a spreadsheet to provide tools in a
      developing armamentarium for extracting information from HTS data. Specific
      examples using two HTS kinase assays are analyzed. The analyses use normal and
      gamma distributions, which combine to form mixture distributions. HTS data were
      found to be described well using such mixture distributions, and deconvolution of
      the mixtures to the constituent gamma and normal parts provided insight into how
      the assays performed. In particular, the proportion of hits confirmed was
      predicted from the original HTS data and used to assess screening assay
      performance. The analyses also provide a method for determining how hit
      thresholds--values used to separate active from inactive compounds--affect the
      proportion of compounds verified as active and how the threshold can be chosen to
      optimize the selection process.

PMID- 17214953
TI  - Developing a verbal protocol method for collecting and analysing reports of
      workers' thoughts during manual handling tasks.
AB  - Concurrent and retrospective verbal protocol methods were used to collect
      thoughts from 18 participants during a manual handling task involving the
      repeated transfer of loads between locations at two tables. The effectiveness of
      qualitative and quantitative methods of analysing the reported information was
      tested in the study. A simple taxonomy was developed to investigate the content
      of the reports (including reports on postures and loads) and determine how the
      participants approached the task (whether they made plans, described actions or
      evaluated their completion of the task). References to posture were obtained in
      the verbal protocol reports, indicating that the participants had some awareness
      of their postures during parts of the task. There were similarities in the
      content of the concurrent and retrospective reports, but there were differences
      in the amount of detail between the methods and differences in the way the
      reports were constructed. There could be some scope for developing the
      quantitative analysis of the frequencies of references to classes of information,
      though this can only be recommended for concurrent reports on tasks of short
      duration. The analyses of qualitative data gave a deeper insight into the
      reports, such as identifying factors that can be important when planning to
      handle a load, or illustrating how participants can change their focus of
      attention periodically throughout the task. The relative strengths of the
      concurrent and retrospective methods are described, along with ideas for
      improving the quality of information collected in future studies. A number of
      potential problems with the interpretation of the reported information are
      explained.

PMID- 17214954
TI  - Investigation on glycosylation patterns of proteins from human liver cancer cell
      lines based on the multiplexed proteomics technology.
AB  - Glycosylation, a very important post-translational modification of proteins, is
      increasingly coming into notice. However, large-scale, throughput investigations
      on glycosylated proteins are few. We applied a sensitive and fast fluorescence
      based multiplexed proteomics (MP) technology which included two-dimensional gel
      electrophoresis (2-DE) followed by the fluorescence staining of glycoprotein and
      mass spectrometry identification for the purpose of constructing glycoprotein
      databases of the typical human hepatocellular carcinoma cell lines including
      Hep3B cell line without metastasis and MHCC97H with highly metastatic potential
      as well as the control non-tumor Chang liver cell. 74+/-2 (n=3), 78+/-3 (n=3) and
      72+/-5 (n=3) glycoprotein spots were detected on 2-DE gels from Chang liver,
      Hep3B and MHCC97H cell sample using this MP technique, respectively. In all, 80
      glycoproteins from three cell lines were successfully identified via peptide mass
      profiling using MALDI-TOF-MS/MS and the identified glycoproteins were annotated
      to our databases. In addition, we also found the glycosylation pattern
      differences among these three cell lines. The protein glycosylation alteration
      would be have great significance for the diagnosis of HCC and prediction of its
      metastasis. This study described the construction of glycosylation patterns of
      proteins and glycoproteome databases of human liver cells by the novel
      technological platform. The glycoproteome databases also provide essential basis
      for following study.

PMID- 17214955
TI  - Heregulinbeta activates store-operated Ca2+ channels through c-erbB2 receptor
      level-dependent pathway in human breast cancer cells.
AB  - The heregulinbeta (HRGbeta) is a ligand to activate c-erbB2/c-erbB3 interaction
      and can subsequently increases cytosolic [Ca(2+)](i). In the two human breast
      cancer cell lines, MCF-7 shows a low c-erbB2 expression level, whereas SK-BR-3
      overexpress c-erbB2 receptor. In this article, we have found that in MCF-7,
      HRGbeta induced Ca(2+) release from the endoplasmic reticulums (ER) and
      subsequently activated Ca(2+) entry via store-operated Ca(2+) channel (SOC).
      However, in SK-BR-3, HRGbeta failed to induce Ca(2+) release and Ca(2+)entry. RNA
      interference to decrease c-erbB2 level in SK-BR-3 resulted in reactivation of
      HRGbeta-evoked Ca(2+) release and Ca(2+) entry via SOC, which was similar to that
      of MCF-7. In addition, in the absence of HRGbeta, a constitutive activation of
      SOC was observed in SK-BR-3 rather than in MCF-7 and c-erbB2-siRNA treated SK-BR
      3. Compared to the cells with low c-erbB2 level, c-erbB2 might tend to interact
      with c-erbB3 in the resting state in the cells with high c-erbB2 level, which
      resulted in different [Ca(2+)](i) responses to HRGbeta. In SK-BR-3, the Ca(2+)
      mobilization in the presence or in the absence of HRGbeta was completely blocked
      by PLC inhibitor U73122. In summary, our results indicate that HRGbeta-induced
      SOC was regulated by c-erbB2 level and dependent on activation of PLC in human
      breast cancer cells.

PMID- 17214956
TI  - Tricyclic antidepressants, but not the selective serotonin reuptake inhibitor
      fluoxetine, bind to the S1S2 domain of AMPA receptors.
AB  - The hypothesis that depression is caused solely by a decrease in synaptic
      availability of monoaminergic neurotransmitters has been questioned over the past
      two decades. Based on accumulating data, it seems more plausible that cross-talk
      exists between neurotransmitters in the CNS, including the glutamatergic system.
      Glutamate, the major fast excitatory neurotransmitter in the CNS, is the natural
      agonist for the ionotropic glutamate receptors, a family of ligand-gated ion
      channels including NMDA (N-methyl-D-aspartate), AMPA (amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid), and kainate receptors. In this work, we show that five
      tricyclic antidepressants bind to the S1S2 domain of the GluR2 subunit of the
      AMPA receptor. A combination of fluorescence quenching, Stern-Volmer analyses,
      and protease protection assays differentiate the binding of each antidepressant.
      These analyses provide no evidence for the binding of the selective serotonin
      reuptake inhibitor, fluoxetine, to this domain. The data presented provides
      further support for a role of the glutamatergic system in antidepressant
      activity.

PMID- 17214957
TI  - Identification of a highly potent vitamin D receptor antagonist: (25S)-26
      adamantyl-25-hydroxy-2-methylene-22,23-didehydro-19,27-dinor-20-epi-vitamin D3
      (ADMI3).
AB  - We synthesized four new vitamin D derivatives, diastereomers at C20 and C25 of 26
      adamantyl-1,25-dihydroxy-2-methylene-22,23-didehydro-19,27-dinorvitamin D3 (ADMI1
      4), which have the bulky and rigid adamantane ring system at the side chain
      terminus. These compounds had significant VDR affinity (1/6-1/30 that of the
      natural hormone) but their efficacies of transactivation in transient
      transcription assay was low (approximately 1/10). All ADMI compounds antagonized
      the action of 1,25(OH)2D3 in transient transcription assay in COS-7 cells with
      ADMI3 (20S,25S-isomer) was the most potent (IC50, 3 nM). ADMI3 (1 microM)
      suppressed the endogenous CYP24A1 gene expression induced by 1,25(OH)2D3 (10 nM)
      in HEK293 cells to nearly control level. Thus we have identified 26-adamantyl
      vitamin D compound as a novel highly potent VDR antagonist/partial agonist. A
      docking model of ADMI3 reveals that a terminal part of the large adamantane ring
      crowds the H12 residues (Val318 and Phe422) and this would prevent the H12
      adopting the active conformation.

PMID- 17214958
TI  - What can human experimental pain models teach us about clinical TMD?
AB  - Human experimental pain (HEP) models applied to the orofacial area have been
      widely used over the last decades and several reviews are available on the
      interaction between HEP and jaw-motor function. In this selective review some of
      the possibilities and limitations with HEP models are discussed based on the
      current experience with HEP models. For example, it is appropriate to consider
      how closely HEP models may mimic the clinical phenomenon, i.e., do they represent
      a reasonable "proxy" of temporomandibular disorders (TMD) and what can HEP models
      offer for the understanding of jaw-motor function in relation to painful TMD
      conditions. Finally, are there any clinical implications of the knowledge derived
      from HEP studies? This present review suggests that HEP models, indeed, are
      valuable and can provide clinically relevant information by serving as a bridge
      between basic animal experiments and studies in pain populations; however, there
      are several caveats to this suggestion which needs to be acknowledged.

PMID- 17214959
TI  - Translocation and nuclear accumulation of monomer and dimer of HIV-1 Tat basic
      domain in triticale mesophyll protoplasts.
AB  - Cellular internalization of cell-penetrating peptide HIV-1 Tat basic domain
      (RKKRRQRRR) was studied in Triticale cv AC Alta mesophyll protoplasts.
      Fluorescently labeled monomer (Tat) and dimer (Tat(2)) of Tat basic domain
      efficiently translocated through the plasma membrane of mesophyll protoplast and
      showed distinct nuclear accumulation within 10 min of incubation. Substitution of
      first arginine residue with alanine in Tat basic domain (M-Tat) severely reduced
      cellular uptake of the peptide (3.8 times less than Tat). Tat(2) showed greater
      cellular internalization than Tat (1.6 times higher). However, characteristics of
      cellular uptake remained same for Tat and Tat(2). Cellular internalization of Tat
      and Tat(2) was concentration dependent and non-saturable whereas no significant
      change in cellular uptake was observed even at higher concentrations of M-Tat.
      Low temperature (4 degrees C) remarkably increased cellular internalization of
      Tat as well as Tat(2) but M-Tat showed no enhanced uptake. Viability test showed
      that peptide treatment had no cytotoxic effect on protoplasts further indicating
      involvement of a common mechanism of peptide uptake at all the temperatures.
      Endocytic inhibitors nocodazole (10 muM), chloroquine (100 muM) and sodium azide
      (5 mM) did not show any significant inhibitory effect on cellular internalization
      of either Tat or Tat(2). These results along with stimulated cellular uptake at
      low temperature indicate that Tat peptide is internalized in the plant
      protoplasts in a non-endocytic and energy-independent manner. Competition
      experiments showed that non-labeled peptide did not inhibit or alter nuclear
      accumulation of fluorescent Tat or Tat(2) suggesting active transport to the
      nucleus was not involved. Studies in mesophyll protoplasts show that
      internalization pattern of Tat peptide is apparently similar to that observed in
      mammalian cell lines.

PMID- 17214960
TI  - Private and public self-awareness in social anxiety.
AB  - Clark and Wells' [(1995). A cognitive model of social phobia. In R.G. Heimberg,
      M. Liebowitz, D.A. Hope, & F. Schneier (Eds.). Social phobia: Diagnosis,
      assessment and treatment. New York: Guildford Press] cognitive model of social
      phobia proposes that self-focused attention and construction of the self as a
      social object maintain anxiety. This study examines the effect of two different
      self-focus manipulations (mirror and video) on public and private self-awareness,
      perspective taking, anxiety, and attributions. Thirty one high socially anxious
      participants (26 female, 5 male) with a mean age of 19.58 (SD=1.89) and 32 low
      socially anxious participants (21 female, 11 male) with a mean age of 20.47
      (SD=3.69) took part in a conversation with a stooge. Public self-awareness
      increased in both groups but was higher overall in the high socially anxious
      group. Private self-awareness decreased for the low socially anxious group, but
      did not change for the high socially anxious group. High socially anxious
      participants were also more aware of their surroundings than low socially anxious
      participants. High socially anxious participants used the field perspective less,
      and experienced more anxiety. High socially anxious participants also made fewer
      internal attributions for the conversation going well and more for the
      conversation going badly than low socially anxious participants who did the
      opposite. The implications of the results for the cognitive model are discussed.

PMID- 17214961
TI  - Principal role of NR3 subunits in NR1/NR3 excitatory glycine receptor function.
AB  - Calcium-permeable N-methyl-d-aspartate (NMDA) receptors are tetrameric cation
      channels composed of glycine-binding NR1 and glutamate-binding NR2 subunits,
      which require binding of both glutamate and glycine for efficient channel gating.
      In contrast, receptors assembled from NR1 and NR3 subunits function as calcium
      impermeable excitatory glycine receptors that respond to agonist application only
      with low efficacy. Here, we show that antagonists of and substitutions within the
      glycine-binding site of NR1 potentiate NR1/NR3 receptor function up to 25-fold,
      but inhibition or mutation of the NR3 glycine binding site reduces or abolishes
      receptor activation. Thus, glycine bound to the NR1 subunit causes auto
      inhibition of NR1/NR3 receptors whereas glycine binding to the NR3 subunits is
      required for opening of the ion channel. Our results establish differential roles
      of the high-affinity NR3 and low-affinity NR1 glycine-binding sites in excitatory
      glycine receptor function.

PMID- 17214962
TI  - Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced
      activation of epidermal growth factor receptor and mitogen-activated protein
      kinases in gastric carcinoma cells.
AB  - Bile acids, which have been implicated in gastrointestinal-tract cell
      carcinogenesis, share properties with tumor promoters in that both affect signal
      transduction pathways responsible for cell proliferation and apoptosis. In the
      present study, we demonstrate that EGFR-ERK1/2 is activated following treatment
      of AGS human gastric carcinoma cells with bile acids. EGFR phosphoactivation is
      ligand-dependent, since treatment of cells with HB-EGF antisera or CM197 (a
      selective inhibitor of HB-EGF) markedly inhibits deoxycholate (DC)-promoted
      activation. Membrane-type bile acid receptor (M-BAR)/TGR5 is a recently
      identified G-protein-coupled receptor (GPCR). In AGS cells, siRNAs that target M
      BAR suppress DC-induced phosphorylation of EGFR. Furthermore, introduction of
      siRNAs targeting ADAM17 transcripts resulted in suppression of DC-induced
      activation of EGFR and ERK1/2. These results suggest that in AGS cells, DC
      transactivates EGFR through M-BAR- and ADAM/HB-EGF-dependent mechanisms.

PMID- 17214963
TI  - DNA methylation and Sp1 binding determine the tissue-specific transcriptional
      activity of the mouse Abcc6 promoter.
AB  - The gene encoding the ABCC6 protein, an ABC transporter of the multidrug
      resistance-associated protein (MRP), is mainly expressed in liver and kidney.
      Mutations in ABCC6 are responsible for the development of the pseudoxanthoma
      elasticum (PXE) phenotype. PXE is a recessive disease characterized by the
      calcification of elastic fibers resulting in dermal, vascular, and ocular
      clinical manifestations. The physiological function of ABCC6 and the rodent
      orthologs Abcc6 is unknown and their precise relationship to elastic fibers is
      only a matter of speculation. Despite several studies focused on the
      transcriptional regulation of ABCC6/Abcc6, the molecular signals conferring the
      tissue-specificity to the ABCC6/Abcc6 expression are not well defined. In this
      report, we determined the level of the mouse Abcc6 promoter methylation in
      tissues with low level of expression (tail extremity and skin), intermediate
      (kidney), and high level of expression (liver). We observed that high and
      moderate levels of methylation correlated with low levels of Abcc6 expression.
      Moreover, we determined that CpG methylation of the Abcc6 proximal promoter
      region was interfering with the binding of the Sp1 transcription factor thereby
      inhibiting Sp1-dependent transactivation. Thus, our data provide the first direct
      evidence that an epigenetic mechanism regulates the binding of transcription
      factor Sp1 to the proximal promoter and participates in the tissue-specific
      expression control of the mouse Abcc6 gene.

PMID- 17214964
TI  - PARP1 Val762Ala polymorphism reduces enzymatic activity.
AB  - Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by
      poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular
      processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762,
      resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic
      domain has been implicated in susceptibility to cancer. To characterize the
      functional effect of this polymorphism on PARP1, we performed in vitro enzymatic
      analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed
      57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9%
      of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1.
      The kinetic characterization revealed that the K(m) of PARP1-Ala762 was increased
      to a 1.2-fold of the K(m) of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus,
      the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by
      increasing K(m). This finding suggests that different levels of poly(ADP
      ribosyl)ation by PARP1 might aid in understanding the cancer risk of carriers of
      the PARP1 Val762Ala polymorphism.

PMID- 17214965
TI  - A neutralizable epitope is induced on HGF upon its interaction with its receptor
      cMet.
AB  - A new conformational neutralizable epitope is created on heptocyte growth factor
      (HGF), when it interacts with its receptor, cMet. By immunizing rabbits with HGF
      cMet complex, we successfully generated a monoclonal antibody (SFN68) that
      inhibits HGF-cMet interaction, and blocks the biological function mediated by
      HGF. To define the epitope, we screened out an epitope-mimicking peptide,
      KSLSRHDHIHHH, from a phage display of combinatorial peptide library. In molecular
      mimicry this peptide bound to cMet and inhibited HGF-cMet interaction. No humoral
      response was induced to this epitope-mimicking peptide when immunization was done
      with HGF alone.

PMID- 17214966
TI  - Bmi1 cooperates with Dnmt1-associated protein 1 in gene silencing.
AB  - Polycomb group (PcG) proteins are involved in gene silencing through chromatin
      modifications. Among polycomb repressive complexes (PRCs), PRC1 exhibits H2A-K119
      ubiquitin E3 ligase activity. However, the molecular mechanisms underlying PRC1
      mediated gene silencing remain largely obscure. In this study, we found that Bmi1
      directly interacts with Dnmt-associated protein 1 (Dmap1), which has been
      characterized to associate with the maintenance DNA methyltransferase, Dnmt1.
      Bmi1 was demonstrated to form a ternary complex with Dmap1 and Dnmt1 with Dmap1
      in the central position. Chromatin immunoprecipitations confirmed the ternary
      complex formation within the context of the PRC1 at the Bmi1 target loci. Loss of
      Dmap1 binding to the Bmi1 target loci was tightly associated with derepressed
      gene expression in Bmi1-/- cells. Dmap1 knockdown exhibited the same impact as
      Bmi1 knockout did on the expression of Bmi1 targets, including Hox genes.
      Collectively, our findings suggest that Bmi1 incorporates Dmap1 in polycomb gene
      silencing.

PMID- 17214967
TI  - ALG-2 oscillates in subcellular localization, unitemporally with calcium
      oscillations.
AB  - A variety of stimuli can trigger intracellular calcium oscillations. Relatively
      little is known about the molecular mechanisms decoding these events. We show
      that ALG-2, a Ca2+-binding protein originally isolated as a protein associated
      with apoptosis, is directly linked to Ca2+ signalling. We discovered that the
      subcellular distribution of a tagged version of ALG-2 could be directed by
      physiological external stimuli (including ATP, EGF, prostaglandin, histamine),
      which provoke intracellular Ca2+ oscillations. Cellular stimulation led to a
      redistribution of ALG-2 from the cytosol to a punctate localization in an
      oscillatory fashion unitemporally with Ca2+ oscillations, whereas a Ca2+-binding
      deficient mutant of ALG-2 did not redistribute. Using tagged ALG-2 as bait we
      identified its novel target protein Sec31A and based on the partial
      colocalization of endogenous ALG-2 and Sec31A we propose that ALG-2 temporarily
      binds to the COPII vesicles providing a link between Ca2+ signalling and ER to
      Golgi trafficking.

PMID- 17214968
TI  - Vanilloid receptor agonists and antagonists are mitochondrial inhibitors: how
      vanilloids cause non-vanilloid receptor mediated cell death.
AB  - Time-lapse photomicroscopy of human H460 lung cancer cells demonstrated of the
      transient receptor potential V1 (TRPV1) channel agonists, (E)-capsaicin and
      resiniferatoxin, and the TRPV1 antagonists, capsazepine, and SB366791, were able
      to bring about morphological changes characteristic of apoptosis and/or necrosis.
      Immunoblot analysis identified immunoreactivity for the transient receptor
      potential V1 (TRPV1) channel in rat brain samples, but not in rat heart
      mitochondria or in H460 cells. In isolated rat heart mitochondria, all four
      ligands caused concentration-dependent decreases in oxygen consumption and
      mitochondrial membrane potential. (E)-Capsaicin and capsazepine evoked
      concentration-dependent increases and decreases, respectively, in mitochondrial
      hydrogen peroxide production, whilst resiniferatoxin and SB366791 were without
      significant effect. These data support the hypothesis that (E)-capsaicin,
      resiniferatoxin, capsazepine, and SB366791 are all mitochondrial inhibitors, able
      to activate apoptosis and/or necrosis via non-receptor mediated mechanisms, and
      also support the use of TRPV1 ligands as anti-cancer agents.

PMID- 17214969
TI  - Dimerization of CtIP may stabilize in vivo interactions with the Retinoblastoma
      pocket domain.
AB  - CtIP is a tumor suppressor that interacts with Retinoblastoma protein (Rb) to
      regulate the G1/S-phase transition of the cell cycle. Despite its large size (897
      residues) CtIP has few known structured regions. Rather it contains several
      linear motifs that interact with known binding partners, including an LXCXE motif
      that binds the pocket domain of Rb-family proteins. This LXCXE motif lies at the
      C-terminus of the only known structured domain, an N-terminal coiled-coil
      dimerization domain (DD; residues 45-160). Yeast two-hybrid (Y2H) and GST
      pulldown analyses showed that CtIP requires the LXCXE motif to bind the Rb
      pocket. Although isothermal titration calorimetry data indicates that the LXCXE
      motif is the sole determinant of binding affinity for the Rb-pocket domain (K(A)
      approximately 10(6)M(-1)), Y2H data indicates that the DD is required to
      stabilize the interaction in vivo. Thus dimerization may increase the apparent
      stability of the proteins and/or the lifetime of the complexes.

PMID- 17214970
TI  - Silibinin suppresses PMA-induced MMP-9 expression by blocking the AP-1 activation
      via MAPK signaling pathways in MCF-7 human breast carcinoma cells.
AB  - Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and
      metastasis of cancer cells. In this study, we examined the inhibitory effect of
      silibinin, a flavonoid antioxidant from milk thistle (Silybum marianum L.) on PMA
      induced MMP-9 expression in MCF-7 human breast carcinoma cells. Silibinin
      significantly and selectively suppressed PMA-induced MMP-9 expression in MCF-7.
      Silibinin has been found to inhibit PMA-induced MMP-9 gene transcriptional
      activity by blocking the activation of AP-1 via MAPK signaling pathways.
      Moreover, the Matrigel invasion assay showed that silibinin reduces PMA-induced
      invasion of MCF-7 cells. These results suggest that silibinin represents a
      potential anti-metastatic agent suppressing PMA-induced cancer cell invasion
      through the specific inhibition of AP-1-dependent MMP-9 gene expression.

PMID- 17214971
TI  - GPR40 is expressed in glucagon producing cells and affects glucagon secretion.
AB  - The free fatty acid receptor, GPR40, has been coupled with insulin secretion via
      its expression in pancreatic beta-cells. However, the role of GPR40 in the
      release of glucagon has not been studied and previous attempts to identify the
      receptor in alpha-cells have been unfruitful. Using double-staining for glucagon
      and GPR40 expression, we demonstrate that the two are expressed in the same cells
      in the periphery of mouse islets. In-R1-G9 hamster glucagonoma cells respond dose
      dependently to linoleic acid stimulation by elevated phosphatidyl inositol
      hydrolysis and glucagon release and the cells become increasingly responsive to
      fatty acid stimulation when overexpressing GPR40. Isolated mouse islets also
      secrete glucagon in response to linoleic acid, a response that was abolished by
      antisense treatment against GPR40. This study demonstrates that GPR40 is present
      and active in pancreatic alpha-cells and puts further emphasis on the importance
      of this nutrient sensing receptor in islet function.

PMID- 17214972
TI  - Quantitative analysis of Akt phosphorylation and activity in response to EGF and
      insulin treatment.
AB  - The protein kinase Akt is a critical regulator of cell function and its
      overexpression and activation have been functionally linked to numerous
      pathologies such as cancer. Previous reports regarding the mechanism-regulating
      Akt's activation have revealed two phosphorylation events, at threonine 308
      (T308) and serine 473 (S473), as necessary for the full activation of the kinase
      in response to insulin. For this reason and because of the availability of
      phospho-specific antibodies to both T308 and S473, many studies that focus on
      Akt's role in governing cell function rely on the measurement of these two sites
      to understand changes in kinase activity. Recent evidence, however, suggests the
      involvement of other phosphorylation sites; for example, in Src-transformed and
      epidermal growth factor (EGF)-treated cells, tyrosine phosphorylation has been
      found important for full kinase activation. In this study, we probed the
      quantitative reliability of using S473 and/or T308 phosphorylation as surrogates
      for Akt kinase activity across diverse treatment conditions. We performed
      quantitative Western blots and kinase activity assays on lysates generated during
      a 2h time course from two cell lines treated with either EGF or insulin. From the
      resulting approximately 250 quantitative measurements of phosphorylation and
      activity, we found that both T308 and S473 phosphorylation accurately captured
      quantitative changes in EGF-stimulated cells, but not in insulin-stimulated
      cells. Moreover, in all but one condition studied, we found a tight correlation
      between the onset of phosphorylation and dephosphorylation for both sites,
      despite the fact that they do not share common kinase- or phosphatase-mediated
      regulation. In sum, using a quantitative approach to study Akt activation
      identified ligand-dependent limits for the use of T308 or S473 as proxies for
      kinase activity and suggests the coregulation of Akt phosphorylation and
      dephosphorylation.

PMID- 17214973
TI  - Structure and function of eritadenine and its 3-deaza analogues: potent
      inhibitors of S-adenosylhomocysteine hydrolase and hypocholesterolemic agents.
AB  - d-Eritadenine (DEA) is a potent inhibitor of S-adenosyl-l-homocysteine hydrolase
      (SAHH) and has hypocholesterolemic activity. We have hypothesized that 3-deaza
      DEA (C3-DEA) and its analogues retain high level of SAHH inhibitory activity and
      have resistance to deamination and glycosidic bond hydrolysis in vivo. Such C3
      DEA analogues would have much higher hypocholesterolemic activity. C3-DEA, and
      its methyl ester (C3-OMeDEA) and its methyl amido (C3-NMeDEA) were synthesized to
      examine their SAHH inhibitory and hypocholesterolemic activities. A crystal
      structure of SAHH containing C3-DEA was determined and confirmed that DEA and C3
      DEA bound to the same site of SAHH with the same binding mode. The SAHH
      inhibitory activities of C3-DEA (K(I)=1.5 microM) and C3-OMeDEA (K(I)=1.5 microM)
      are significantly lower than that of DEA (K(I)=30 nM), while rats fed by C3-DEA
      and C3-OMeDEA decrease the total plasma cholesterol and phospholipids by 36-40%
      and 23%, respectively, which is similar to the level of reductions (42% and 27%)
      by DEA. C3-NMeDEA lost most of the SAHH inhibitory activity (K(I)=30 microM) and
      dietary C3-NMeDEA does not decrease cholesterol and phospholipid in plasma but
      decreases the triacylglycerol level by 16%. DEA and C3-DEA analogues are neither
      substrates nor inhibitors of adenosine deaminase.

PMID- 17214974
TI  - Differential effects of ciproxifan and nicotine on impulsivity and attention
      measures in the 5-choice serial reaction time test.
AB  - Deficits in attention and response inhibition are apparent across several
      neurodegenerative and neuropsychiatric disorders for which current
      pharmacotherapy is inadequate. While it is difficult to model such executive
      processes in animals, the 5-choice serial reaction time test (5-CSRTT), which
      originated from the continuous performance test (CPT) in humans, may serve as a
      useful translational assay for efficacy in these key behavioral domains. At Wyeth
      and Abbott, we recently investigated the utility of employing the 5-CSRTT in
      adult rats. This involved training and testing groups of rats over an extended
      period of several months and required the animals to learn to nose-poke into one
      of five apertures following presentation of a brief visual stimulus in that
      aperture in order to obtain a food reward. When the stimulus duration was short,
      the rat had to pay close attention to make a correct choice--a nose-poke into the
      aperture with the brief visual stimulus. We evaluated nicotine and the histamine
      H(3) receptor antagonist, ciproxifan, since compounds targeting both nicotinic
      and histaminergic neurotransmission are currently under investigation for
      treating cognitive dysfunction in ADHD, AD and schizophrenia. After approximately
      12 weeks of training, rats were tested with drug when they had achieved stable
      performance. Nicotine (0.2, 0.4 mg/kg s.c.) significantly improved accuracy and
      reduced errors of omission (reflecting improved attention and vigilance) when
      baseline performance was <90% correct. In contrast, nicotine tended to worsen
      accuracy when baseline performance was >90% correct. Using the same test
      paradigm, ciproxifan (3mg/kg i.p.) reduced premature responding, a measure of
      impulsivity. Under conditions of variable stimulus duration, ciproxifan also
      improved accuracy and decreased impulsivity. In summary, we have replicated
      previous findings by others of positive effects of nicotine on attention, but
      also showed that this is dependent on baseline performance. We also expanded on
      previous positive findings by others with ciproxifan on attention and both Wyeth
      and Abbott demonstrate for the first time decreased impulsivity with this
      mechanism.

PMID- 17214975
TI  - Relaxin receptors in hepatic stellate cells and cirrhotic liver.
AB  - The polypeptide hormone relaxin has antifibrotic effects on a number of tissues,
      including the liver. Central to the progression of hepatic fibrosis is the
      transdifferentiation of hepatic stellate cells (HSC) from a quiescent state to an
      activated, myofibroblastic phenotype that secretes fibrillar collagen. Relaxin
      inhibits markers of HSC activation, but relaxin receptor expression in the liver
      is unclear. The purpose of this study was to determine the expression of the
      relaxin receptors LGR7 and LGR8 in activated HSC. Production of cAMP was induced
      by treatment of HSC with relaxin, or the relaxin-related peptides InsL3 or
      relaxin-3, selective activators of LGR8 and LGR7, respectively. Quiescent HSC
      expressed low levels of LGR7 but not LGR8. During progression to the activated
      phenotype, expression of both receptors increased markedly. Immunocytochemistry
      confirmed the presence of both receptors in activated HSC. In normal rat liver,
      LGR7, but not LGR8, was expressed at low levels. In cirrhotic liver, expression
      of both receptors significantly increased. Neither receptor was detectable in
      normal liver by immunohistochemistry, but both LGR7 and LGR8 were readily
      detectable in cirrhosis. These results were confirmed in human cirrhotic tissue,
      with the additional finding of occasional perisinusoidal LGR7 immunoreactivity in
      non-cirrhotic tissue. In conclusion, the expression of LGR7 and LGR8 is increased
      with activation of HSC in culture. Cirrhosis also caused increased expression of
      both receptors. Therefore, agents that stimulate LGR8 and LGR7 may be
      therapeutically useful to limit the activation of hepatic stellate cells in liver
      injury.

PMID- 17214976
TI  - The alpha2 adrenoreceptor agonist clonidine suppresses evoked and spontaneous
      seizures, whereas the alpha2 adrenoreceptor antagonist idazoxan promotes seizures
      in amygdala-kindled kittens.
AB  - Microinfusion of alpha2 adrenoreceptor agonists and antagonists into amygdala has
      contrasting effects on evoked and spontaneous seizure susceptibility in amygdala
      kindled kittens. Subjects were 14 preadolescent kittens between 3 and 4 months
      old at the beginning of kindling. The same protocol was followed except that half
      the kittens received microinfusions (1 mul) of the alpha2 agonist clonidine
      (CLON; 1.32 nmol), and half received the alpha2 antagonist idazoxan (IDA; 0.33
      nmol). Infusions were made over 1 min through needles inserted into cannulae
      adjacent to stimulating electrodes in the kindled amygdala, and evoked seizures
      were tested 10-12 min later. The results were: (1) CLON elevated seizure
      thresholds obtained once at the beginning and end of kindling, but only when
      compared to sham control values (needle insertion only) in the same animals; IDA
      significantly reduced thresholds. (2) CLON retarded and IDA accelerated kindling
      rate, defined as the number of afterdischarges (ADs) required to achieve the
      first stage 6 seizure or generalized tonic-clonic convulsion (GTC). These effects
      were most pronounced on the emergence of seizure "generalization" stages (3-6)
      from "focal" seizure stages (1-2). (3) CLON prevented onset of spontaneous
      seizures, whereas IDA precipitated onset of spontaneous seizures in 100% of the
      animals before or during the 5-week post-kindling follow-up during which seizures
      were evoked once each work day. The study confirms previous findings in kindled
      rodents to show that CLON and IDA can have opposing effects on kindling
      development in kittens and is the first report to show contrasting effects on
      spontaneous epileptogenesis in kindled animals as well.

PMID- 17214977
TI  - Transient expression of Nxf, a bHLH-PAS transactivator induced by neuronal
      preconditioning, confers neuroprotection in cultured cells.
AB  - Cortical spreading depression (CSD) induces waves of neuronal depolarization that
      confer neuroprotection to subsequent ischemic events in the rat brain. To gain
      insights into the molecular mechanisms elicited by CSD, we used representational
      difference analysis (RDA) to identify mRNAs induced by potassium depolarization
      in vivo. Using this approach, we have isolated a cDNA encoding the SIM2-related
      bHLH-PAS protein Nxf. Our results confirm that Nxf mRNA and protein are rapidly
      and transiently expressed in cortical neurons following CSD. Reporter assays show
      that Nxf is a transcriptional activator that associates with the bHLH-PAS sub
      class co-factor ARNT2. Adenovirus-mediated expression of epitope-tagged Nxf
      results in cell death and the direct activation of the Bax gene in cultured
      cells. However, RNA interference studies show that endogenous Nxf is required for
      optimal neuroprotection by preconditioning in cultured F-11 cells. Together, our
      data indicate that Nxf is a novel bHLH-PAS transactivator transiently induced by
      preconditioning and that its sustained expression is detrimental. The
      identification of Nxf may represent an important step in our understanding of the
      molecular mechanisms of brain preconditioning and injury.

PMID- 17214978
TI  - Pairing morphology with gene expression in thyroid hormone-induced intestinal
      remodeling and identification of a core set of TH-induced genes across tadpole
      tissues.
AB  - Thyroid hormone (T3) plays a central role in vertebrate post-embryonic
      development, and amphibian metamorphosis provides a unique opportunity to examine
      T3-dependent developmental changes. To establish a molecular framework for
      understanding T3-induced morphological change, we identified a set of gene
      expression profiles controlled by T3 in the intestine via microarray analysis.
      Samples were obtained from premetamorphic Xenopus laevis tadpole intestines after
      0, 1, 3, and 6 days of T3 treatment, which induces successive cell death and
      proliferation essential for intestinal remodeling. Using a set of 21,807 60-mer
      oligonucleotide probes representing >98% of the Unigene clusters, we found that
      1997 genes were differentially regulated by 1.5-fold or more during this
      remodeling process and were clustered into four temporal expression profiles;
      transiently up- or downregulated and late up- or downregulated. Gene Ontology
      categories most significantly associated with these clusters were proteolysis,
      cell cycle, development and transcription, and electron transport and metabolism,
      respectively. These categories are common with those found for T3-regulated genes
      from brain, limb, and tail, although more than 70% of T3-regulated genes are
      tissue-specific, likely due to the fact that not all genes are annotated into GO
      categories and that GO categories common to different organs also contain genes
      regulated by T3 tissue specifically. Finally, a core set of upregulated genes,
      most previously unknown to be T3-regulated, were identified and enriched in genes
      involved in transcription and cell signaling.

PMID- 17214979
TI  - How pollen tubes grow.
AB  - Sexual reproduction of flowering plants depends on delivery of the sperm to the
      egg, which occurs through a long, polarized projection of a pollen cell, called
      the pollen tube. The pollen tube grows exclusively at its tip, and this growth is
      distinguished by very fast rates and reaches extended lengths. Thus, one of the
      most fascinating aspects of pollen biology is the question of how enough cell
      wall material is produced to accommodate such rapid extension of pollen tube, and
      how the cell wall deposition and structure are regulated to allow for rapid
      changes in the direction of growth. This review discusses recent advances in our
      understanding of the mechanism of pollen tube growth, focusing on such basic
      cellular processes as control of cell shape and growth by a network of cell wall
      modifying enzymes, molecular motor-mediated vesicular transport, and
      intracellular signaling by localized gradients of second messengers.

PMID- 17214980
TI  - Enhanced activity of mefloquine and artesunic acid against Plasmodium falciparum
      in vitro and P. berghei in mice by combination with ciprofloxacin.
AB  - The antimalarial activity of combinations of mefloquine or artesunic acid with
      ciprofloxacin and other synthetic fluoroquinolone was tested in vitro against
      Plasmodium falciparum using a strain (BHz26/86) partially resistant to
      chloroquine and a resistant clone (W2); both are sensitive to mefloquine.
      Inhibition of parasite growth was measured in relation to controls without drugs,
      either by counting parasitemia in Giemsa-stained blood smears or by measuring the
      reduction in [(3)H]-hypoxanthine uptake. Combinations containing artesunic acid
      or mefloquine with ciprofloxacin had significant in vitro activity, inhibiting by
      more than 90% of the growth of both strains of P. falciparum at doses
      significantly lower than those of the antimalarials alone. When tested in mice
      inoculated with P. berghei chloroquine-sensitive parasites (NK65 strain),
      ciprofloxacin was inactive, whereas mefloquine and artesunic acid were active
      (IC(50)=2.5 and 4.2 mg/kg, respectively); combinations containing mefloquine at
      an equivalent dose of 0.5 mg/kg reduced parasitemia by 59% and artesunic acid
      activity was also improved by ciprofloxacin. Our data support the idea that
      ciprofloxacin in combination with antimalarials may be useful in the treatment of
      chloroquine-resistant human malaria, allowing the use of lower doses of these
      drugs.

PMID- 17214981
TI  - Differential effects of Ca(2+) on bisphosphonate-induced growth inhibition in
      breast cancer and mesothelioma cells.
AB  - Bisphosphonates are widely clinically used inhibitors of bone resorption. Pre
      clinical studies indicate that bisphosphonates also inhibit the growth of various
      cancer cells in vitro, but their in vivo anti-cancer activity varies greatly,
      depending on the tumor type. We compared the various cellular effects of
      bisphosphonates in breast cancer and mesothelioma cells, with differences in
      growth inhibition responses to bisphosphonate-treatment in vivo. We show that the
      growth inhibitory effects of nitrogen-containing bisphosphonates are
      significantly affected by excess Ca(2+) in a cell- and bisphosphonate-specific
      fashion. Furthermore, excess pyrophosphate-resembling bisphosphonates prevent
      nitrogen-containing-bisphosphonate-induced accumulation of unprenylated Rap1A,
      p38 phosphorylation and growth inhibition in human MDA-MB-231 breast cancer and
      mouse AB-12 mesothelioma cells. For some, but not all tested, pyrophosphate
      resembling bisphosphonate: nitrogen-containing bisphosphonate combinations these
      results may be partially explained by the ability of the excess pyrophosphate
      resembling bisphosphonates to chelate Ca(2+). In mice, subcutaneous AB-12 and MDA
      MB-231 tumors exhibit positive staining for Ca(2+) minerals, as revealed with Von
      Kossa stainings. We further show that the AB-12 tumors accumulate significantly
      more of the bone scanning bisphosphonate, Tc99m-medronate, as compared with MDA
      MB-231 tumors. In conclusion, our results suggest that Ca(2+) regulates the
      growth inhibitory effects of bisphosphonates in a target cell and drug-specific
      fashion. These findings may be of physiological relevance since many tumor types
      are calcified. They further suggest that bisphosphonates can accumulate in tumors
      that are growing at the visceral sites and that differences in tumor accumulation
      of bisphosphonates may regulate their in vivo sensitivity to these drugs.

PMID- 17214982
TI  - Selective inhibition of Kir currents by antihistamines.
AB  - In the present study, the effects of antihistamines on inwardly rectifying
      potassium (Kir) channels expressed in Xenopus oocyte were investigated using two
      electrode voltage clamp technique. Firstly, effects of antihistamines on two
      members of Kir2.0 sub-family, Kir2.1 and Kir2.3 were compared. For antihistamines
      that selectively block histamine H(1) receptor, the first-generation
      antihistamines mepyramine and diphenhydramine inhibited Kir2.3 current by 25.0+/
      2.9% and 17.3+/-0.7% at concentrations of 100 microM, respectively. In contrast,
      the second- and third-generation antihistamines astemizole and desloratadine were
      completely devoid of any inhibitory effect on Kir2.3 current. Histamine H(2)
      receptor antagonist cimetidine, at 100 microM, failed to inhibit Kir2.3 current.
      On the other hand, Kir2.1 current was not sensitive to any of these drugs. The
      mepyramine-induced inhibition of Kir2.3 current was significantly reduced by a
      single point mutation in Kir2.3 (Kir2.3(I213L)), which enhances Kir2.3-PIP(2)
      interaction. Secondly, the effect of mepyramine was also tested on Kir3.4*,
      another member of Kir family. 100 microM mepyramine produced a 30.3+/-4.6%
      inhibition on Kir3.4* current. These results suggest that the first-generation
      histamine H(1) receptor antagonists selectively inhibit Kir currents. The
      inhibitory effect of antihistamines on Kir currents may be involved in their
      neuronal and cardiac toxic effects caused by drug overdosing.

PMID- 17214983
TI  - Bortezomib-induced peripheral neurotoxicity: a neurophysiological and
      pathological study in the rat.
AB  - Bortezomib is a new proteasome inhibitor with a high antitumor activity, but also
      with a potentially severe peripheral neurotoxicity. To establish a preclinical
      model and to characterize the changes induced on the peripheral nerves, dorsal
      root ganglia (DRG) and spinal cord, bortezomib was administered to Wistar rats
      (0.08, 0.15, 0.20, 0.30 mg/kg/day twice [2q7d] or three times [3q7d] weekly for a
      total of 4 weeks). At baseline, on days 14, 21 and 28 after the beginning the
      treatment period and during a 4-week follow-up period sensory nerve conduction
      velocity (SNCV) was determined in the tail of each animal. Sciatic nerve, DRG and
      spinal cord specimens were processed for light and electron microscope
      observations and morphometry. At the maximum tolerated dose bortezomib induced a
      significant reduction in SNCV, with a complete recovery at the end of the follow
      up period. Sciatic nerve examination and morphometric determinations demonstrated
      mild to moderate pathological changes, involving predominantly the Schwann cells
      and myelin, although axonal degeneration was also observed. Bortezomib-induced
      changes were also observed in DRG and they were represented by satellite cell
      intracytoplasmatic vacuolization due to mitochondrial and endoplasmic reticulum
      damage, closely resembling the changes observed in sciatic nerve Schwann cells.
      Only rarely did the cytoplasm of DRG neurons has a dark appearance and clear
      vacuoles occurring in the cytoplasm. Spinal cord was morphologically normal. This
      model is relevant to the neuropathy induced by bortezomib in the treatment of
      human malignancies and it could be useful in increasing our knowledge regarding
      the mechanisms underlying bortezomib neurotoxicity.

PMID- 17214985
TI  - Possible direct involvement of the active-site [4Fe-4S] cluster of the GcpE
      enzyme from Thermus thermophilus in the conversion of MEcPP.
AB  - The GcpE enzyme converts 2-C-methyl-D-erythritol-2,4-cyclodiphosphate (MEcPP)
      into (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) in the penultimate
      step of the DOXP pathway for isoprene biosynthesis. Purification of the enzyme
      under exclusion of air leads to a preparation that contains solely [4Fe-4S]
      clusters. Kinetic studies showed that in the presence of the artificial reductant
      dithionite and MEcPP a new transient iron-sulfur-based signal is detected in
      electron paramagnetic resonance (EPR) spectroscopy. Similarity of this EPR signal
      to that detected in ferredoxin:thioredoxin reductase indicates that during the
      reaction an intermediate is directly bound to the active-site cluster.

PMID- 17214984
TI  - Increased dietary sodium alters Fos expression in the lamina terminalis during
      intravenous angiotensin II infusion.
AB  - These studies examined the effects of increased dietary sodium on expression of
      Fos, the protein product of c-fos, in forebrain structures in the rat following
      intravenous infusion with angiotensin II (AngII). Animals were provided with
      either tap water (Tap) or isotonic saline solution (Iso) as their sole drinking
      fluid for 3-5 weeks prior to testing. Rats were then implanted with catheters in
      a femoral artery and vein. The following day, the conscious, unrestrained animals
      received iv infusion of either isotonic saline (Veh), AngII, or phenylephrine
      (Phen) for 2 h. Blood pressure and heart rate were monitored continuously
      throughout the procedure. Brains were subsequently processed for evaluation of
      Fos-like immunoreactivity (Fos-Li IR) in the organum vasculosum of the lamina
      terminalis (OVLT), the subfornical organ (SFO), and the median preoptic nucleus
      (MnPO). Fos-Li IR was significantly increased in the SFO and OVLT of animals
      consuming both Tap and Iso following AngII, but not Phen, compared to Veh
      infusions. Furthermore, Fos-Li IR in the MnPO was increased following AngII
      infusion in rats consuming a high sodium diet, but not in animals drinking Tap.
      These data suggest that increased dietary sodium sensitizes the MnPO neurons to
      excitatory input from brain areas responding to circulating AngII.

PMID- 17214986
TI  - Co-evolution of the archaeal tRNA-dependent amidotransferase GatCAB with
      tRNA(Asn).
AB  - The important identity elements in tRNA(Gln) and tRNA(Asn) for bacterial GatCAB
      and in tRNA(Gln) for archaeal GatDE are the D-loop and the first base pair of the
      acceptor stem. Here we show that Methanothermobacter thermautotrophicus GatCAB,
      the archaeal enzyme, is different as it discriminates Asp-tRNA(Asp) and Asp
      tRNA(Asn) by use of U49, the D-loop and to a lesser extent the variable loop.
      Since archaea possess the tRNA(Gln)-specific amidotransferase GatDE, the archaeal
      GatCAB enzyme evolved to recognize different elements in tRNA(Asn) than those
      recognized by GatDE or by the bacterial GatCAB enzyme in their tRNA substrates.

PMID- 17214987
TI  - Mutational analysis of conserved aromatic residues in the A-loop of the ABC
      transporter ABCB1A (mouse Mdr3).
AB  - The A-loop is a recently described conserved region in the NBDs of ABC
      transporters [Ambudkar, S.V., Kim, I.-W., Xia, D. and Sauna, Z.E. (2006) The A
      loop, a novel conserved aromatic acid subdomain upstream of the Walker A motif in
      ABC transporters, is critical for ATP binding. FEBS Lett. 580, 1049-1055; Kim,
      I.W., Peng, X.H., Sauna, Z.E., FitzGerald, P.C., Xia, D., Muller, M., Nandigama,
      K. and Ambudkar, S.V. (2006) The conserved tyrosine residues 401 and 1044 in ATP
      sites of human P-glycoprotein are critical for ATP binding and hydrolysis:
      evidence for a conserved subdomain, the A-loop in the ATP-binding cassette.
      Biochemistry 45, 7605-7616]. In mouse P-glycoprotein (Abcb1a), the aromatic
      residue of the A-loop in both NBDs is a tyrosine: Y397 in NBD1 and Y1040 in NBD2.
      Another tyrosine residue (618 in NBD1 and 1263 in NBD2) also appears to lie in
      proximity to the ATP molecule. We have mutated residues Y397, Y618, Y1040, and
      Y1263 to tryptophan and analyzed the effect of these substitutions on transport
      properties, ATP binding, and ATP hydrolysis by Abcb1a (mouse Mdr3). Y618W and
      Y1263W enzymes had catalytic characteristics similar to WT Abcb1a. On the other
      hand, Y397W and Y1040W showed impaired transport and greatly reduced ATPase
      activity, including a approximately 10-fold increase in Km for MgATP. Thus, Y397
      and Y1040 play an important role in Abcb1a catalysis.

PMID- 17214988
TI  - Lisfranc injury: how frequently does it get missed? And how can we improve?
AB  - Lisfranc injuries are sometimes easily missed especially if they present in a
      subtle form. In this study, we have tried to measure the level of accuracy of
      plain radiographs in detecting this type of injury. We have selected 30 sets of
      foot radiographs with various diagnoses. Eighteen of them had a Lisfranc type of
      injury which was confirmed by operative findings or further imaging. These
      radiographs, together with a small diagnostic questionnaire, were presented to
      nine senior clinicians. We found that only 11 of the 18 cases (61%) were detected
      by all the readers. Eight of nine readers (90%) missed one particular case of
      subtle Lisfranc injury in a diabetic neuropathic foot. One case of a divergent
      injury was missed by five readers (56%). Another case with a coexistent
      Frieberg's disease was missed by three readers (33%). The mean accuracy for all
      injuries was 87% (95% confidence interval (CI) 84.6-89.9%). The mean accuracy
      level for detection of Lisfranc injury among the whole series was 92% (CI 89
      95%). We think that the presence of a strong clinical index of suspicion or the
      presence of impaired pain sensation, further imaging is a must to avoid missing
      this type of injury at early presentation, and consequently the long term poor
      prognosis.

PMID- 17214989
TI  - Early coagulopathy in multiple injury: an analysis from the German Trauma
      Registry on 8724 patients.
AB  - BACKGROUND: There is increasing evidence for acute traumatic coagulopathy
      occurring prior to emergency room (ER) admission but detailed information is
      lacking. PATIENTS AND METHODS: A retrospective analysis using the German Trauma
      Registry database including 17,200 multiple injured patients was conducted to
      determine (a) to what extent clinically relevant coagulopathy has already been
      established upon ER admission, and whether its presence was associated (b) with
      the amount of intravenous fluids (i.v.) administered pre-clinically, (c) with the
      magnitude of injury, and (d) with impaired outcome and mortality. Eight thousand
      seven hundred and twenty-four patients with complete data sets were screened.
      RESULTS: Coagulopathy upon ER admission as defined by prothrombin time test
      (Quick's value) <70% and/or platelets <100,000 microl(-1), was present in 34.2%
      of all patients. There was an increasing incidence for coagulopathy with
      increasing amounts of i.v. fluids administered pre-clinically. Coagulopathy was
      observed in >40% of patients with >2000 ml, in >50% with >3000 ml, and in >70%
      with >4000 ml administered. Ten percentage of patients presented with clotting
      disorders although pre-clinical resuscitation was limited to 500 ml of i.v.
      fluids maximum. The mean ISS score in the coagulopathy group was 30 (S.D. 15)
      versus 21 (S.D. 12) (p<0.001). Twenty-nine percentage of patients with
      coagulopathy developed multi organ failure (p<0.001). Early in-hospital mortality
      (<24h) was 13% in patients with coagulopathy (p<0.001) and overall in-hospital
      mortality totalled 28% (p<0.001). CONCLUSION: There is a high frequency of
      established coagulopathy in multiple injury upon ER admission. The presence of
      early traumatic coagulopathy was associated with the amount of intravenous fluids
      administered pre-clinically, magnitude of injury, and impaired outcome.

PMID- 17214990
TI  - Increased atherosclerosis following treatment with a dual PPAR agonist in the
      ApoE knockout mouse.
AB  - OBJECTIVE: Recent reports have suggested that dual peroxisome proliferator
      activated receptor (PPAR) alpha/gamma agonists are associated with adverse
      cardiovascular events. This study aimed to investigate the actions of the non
      thiazolidinedione PPARalpha/gamma agonist, compound 3q, on plaque development in
      the apolipoprotein E knockout (apoE KO) mouse, a recognised model of accelerated
      plaque development. METHODS: Six-week-old male apoE KO mice were randomised to
      receive the dual PPARalpha/gamma agonist, compound 3q (3 mg/kg/day), the
      PPARgamma agonist, rosiglitazone (20 mg/kg/day), the PPARalpha agonist,
      gemfibrozil (100 mg/kg/day) by gavage or no treatment for 20 weeks (n=12/group).
      RESULTS: Gemfibrozil and rosiglitazone significantly reduced lesion area.
      However, compound 3q was associated with a three-fold increase in total plaque
      area (versus control p<0.001). This was associated with an upregulation of
      markers of plaque instability including vascular cell adhesion molecule-1 (3.5
      fold, p<0.001), P-selectin (3.4-fold, p<0.001) monocyte chemoattractant protein-1
      (3.4-fold; p<0.001) as well as the scavenger receptor, CD36 (2-fold, p<0.01).
      These disparate effects were observed with the dual PPAR agonist despite lowering
      LDL cholesterol and improving insulin sensitivity to a similar extent to
      PPARalpha and gamma agonists used individually. CONCLUSION: The finding of
      increased atherogenesis following a dual PPARalpha/gamma agonist is consistent
      with recent clinical findings. These data provide an important framework for
      further exploring the potential utility and safety of combinatorial approaches.

PMID- 17214991
TI  - SHP-2 and PI3-kinase genes PTPN11 and PIK3R1 may influence serum apoB and LDL
      cholesterol levels in normal women.
AB  - Insulin regulates apoB metabolism via activation of PI3K or regulation of MTP via
      MAPK/ERK signalling. SHP-2 enhances both pathways through increased IRS-1
      phosphorylation. We hypothesized that variants in the SHP-2 gene PTPN11 and PI3K
      p85alpha subunit gene PIK3R1 may influence fasting levels of plasma apoB and/or
      LDL cholesterol. We tested association of tagging SNPs (tSNPs) in each gene with
      serum lipids in a large sample of unselected population-based Caucasian female
      twins (n=2771, mean age 47.4+/-12.5 years) and then tested interaction between
      tSNPs in determining apoB and LDL levels. PTPN11 tSNP rs11066322 was associated
      with apoB (P=0.007) and rs11066320 was associated with LDL cholesterol (P=0.016).
      PIK3R1 tSNP rs251406 was associated with apoB (P=0.0003) and rs706713 was
      associated with LDL cholesterol (P=0.009). PTPN11 tSNP rs11066322 interacted with
      PIK3R1 tSNP rs251406 in determining serum apoB levels (P=0.012) and with PIK3R1
      tSNP rs40318 in determining LDL cholesterol levels (P=0.009). Association of
      single tSNPs with both apoB and LDL cholesterol as well as interactions between
      the two genes suggest that variants influencing SHP-2 activity may modulate the
      acute pathway by which insulin regulates these lipids.

PMID- 17214992
TI  - Tesaglitazar, a dual peroxisome proliferator-activated receptor alpha/gamma
      agonist, reduces atherosclerosis in female low density lipoprotein receptor
      deficient mice.
AB  - OBJECTIVE: The transcription factors, peroxisome proliferator-activated receptors
      (PPAR) alpha (alpha) and gamma (gamma), which are involved in lipid and glucose
      homeostasis, also exert modulatory actions on vascular cells where they exhibit
      anti-inflammatory and anti-proliferative properties. Hence, PPAR agonists
      potentially can affect atherogenesis both via metabolic effects and direct
      effects on the vessel wall. We tested whether the dual PPAR-alpha/gamma agonist,
      tesaglitazar (TZ), would reduce atherosclerosis in a non-diabetic,
      atherosclerosis-prone mouse model, independent of effects on plasma lipids.
      METHODS AND RESULTS: Low-density lipoprotein receptor deficient (LDLr-/-) mice
      were fed a Western type diet consisting of 21% butterfat and 0.15% cholesterol,
      with or without TZ 0.5 micromol/kg of diet, for 12 weeks. TZ reduced
      atherosclerosis in the female, but not male, LDLr-/- mice without affecting
      cholesterol and triglyceride levels, HDL binding to biglycan, or the inflammatory
      markers serum amyloid A (SAA) and serum amyloid P (SAP). TZ also decreased
      adiposity in both genders. CONCLUSIONS: TZ reduced atherosclerosis in the female
      LDLr-/- mice via lipid-independent mechanisms, probably at least in part by
      direct actions on the vessels. The body weight changes in these mice are
      different from the effects of dual PPAR agonists seen in humans.

PMID- 17214993
TI  - Effects of the antioxidant succinobucol (AGI-1067) on human atherosclerosis in a
      randomized clinical trial.
AB  - BACKGROUND: The antioxidant AGI-1067 was shown to reduce experimental
      atherosclerosis. The present study originally intended to study restenosis as a
      primary endpoint but was subsequently modified to primarily investigate the
      effects of AGI-1067 on coronary atherosclerosis. METHODS AND RESULTS: This
      placebo-controlled randomized trial assessed the effects of AGI-1067 280 mg qd
      started before percutaneous coronary intervention (PCI) and administered for 12
      months after PCI on atherosclerosis progression as assessed by coronary
      intravascular ultrasound (IVUS). Among patients with IVUS examinations considered
      technically adequate both at baseline and follow-up upon central laboratory
      assessments (n=232), plaque volume was not significantly modified with placebo
      (least squares mean change: -0.4mm(3), P=0.85 versus baseline), but was
      significantly reduced by -4.0mm(3) at end of treatment in the AGI-1067 group
      (P=0.001 versus baseline, P=0.12 versus placebo). LDL-cholesterol varied by -9%
      and +4% in the placebo and AGI-1067 groups, respectively (P<0.05 between groups),
      and HDL-cholesterol was reduced by 1% with placebo and 14% with AGI-1067 (P<0.05
      between groups). Plasma myeloperoxidase was reduced by 6% with AGI-1067 (P<0.05)
      but hs-CRP was not significantly different between groups. CONCLUSIONS:
      Atherosclerosis regression (-4.0mm(3)) was observed in patients treated with AGI
      1067, although this was not significantly different from placebo. The anti
      inflammatory effect of AGI-1067 is supported by reduced levels of
      myeloperoxidase.

PMID- 17214994
TI  - NAD(P)H oxidase polymorphism (C242T) and high HDL cholesterol associate with
      recurrent coronary events in postinfarction patients.
AB  - We recently identified a subgroup of postinfarction patients at high-risk for
      recurrent coronary events defined by inflammation (high C-reactive protein) (CRP)
      and hypercholesterolemia. Within this subgroup, only elevated high-density
      lipoprotein cholesterol (HDL-C) from a set of metabolic, inflammatory and
      thrombogenic blood markers was associated with additional risk. To investigate
      the role of oxidative stress in this high-risk subgroup, we examined effects on
      risk of a polymorphism known to affect functional activity of NAD(P)H oxidase, an
      oxidative enzyme associated with generation of reactive oxygen species. The study
      population comprised non-diabetic patients of thrombogenic factors and recurrent
      coronary events (THROMBO) postinfarction study having complete blood marker and
      genotyping results (N=663) for C242T polymorphism of p22phox subunit (T allele
      associated with decreased activity). Cox multivariable regression, adjusted for
      significant clinical covariates, was used to assess within-subgroup risk
      associated with blood markers and polymorphism. In addition to elevated HDL-C
      (hazard ratio, 95% CI and p-value; 2.62, 1.05-6.55 and 0.039), significant
      independent risk was found for C242T (CC versus CT plus TT: 3.14, 1.34-7.35 and
      0.0084). We conclude that oxidative stress plays a significant role in
      establishment of risk for recurrent coronary events in a high-risk subgroup of
      postinfarction patients defined by inflammation and hypercholesterolemia.

PMID- 17214995
TI  - Autoantibody against the amino acid sequence 661-680 in apo B-100 is associated
      with decreased carotid stenosis and cardiovascular events.
AB  - Immunization with malondialdehyde (MDA)-modified peptides corresponding to the
      amino acid sequence between 661 and 680 in apo B-100 (p45) inhibits
      atherosclerosis in apo E knockout mice. The same effect can be obtained by
      treating the mice with recombinant anti-MDA-p45 IgG, suggesting that these
      antibodies have atheroprotective effects. In the present study we analyzed if
      autoantibodies against p45 and MDA-p45 are related to carotid atherosclerosis and
      acute cardiovascular events in humans. Using a nested case control design we
      determined plasma levels of IgG recognizing native and MDA-modified p45 in
      baseline samples from 75 subjects with acute myocardial infarction or sudden
      cardiac death and 148 matched controls. The control group was found to have
      significantly higher levels of p45 IgG than the cases. Moreover, an independent
      association was found between high levels of MDA-p45 IgG and a low degree of
      carotid stenosis (P=0.006). There was a high degree of co-variation between IgG
      binding to native p45 and MDA-p45 (r=0.68, P<0.0001). The associations between
      lower levels of autoantibodies against the apo B-100 p45 sequence and
      cardiovascular disease are in agreement with previous experimental studies
      demonstrating that these antibodies have atheroprotective effects. Our findings
      support the notion that the p45 sequence of apo B-100 is a potential target for
      immunomodulatory treatment of atherosclerosis in humans.

PMID- 17214997
TI  - Establishing the feasibility of coupled solid-phase extraction-solid-phase
      derivatization for acidic herbicides.
AB  - The significance of this research is that it improves analytical methodology used
      for organic chemicals in aqueous solutions by establishing the feasibility of
      heterogeneous chemical derivatization at the liquid-solid interface (i.e., solid
      phase reaction or solid-phase derivatization). A solid-phase derivatization
      method for determining chlorinated herbicide acids was developed. Solid-phase
      extraction was used to concentrate and retain analytes on sorbents for subsequent
      solid-phase derivatization. Background interferences were removed from the
      chromatograms by electronically subtracting the responses of blank, nonfortified
      analyses from spiked samples. Two extraction sorbents (octadecyl bonded silica
      and polystyrene-divinylbenzene) and two derivatizing reagents (BF3-MeOH and
      trimethylsilyldiazomethane) were investigated. Recovery of 13 chlorinated
      herbicide acids--including pentachlorophenol, dinoseb, and bentazon (having a
      derivatizable functional group, -OH or -NH, bonded directly to a phenyl group);
      dicamba, picloram, acifluorfen, 3,5-dichlorobenzoic acid, and dacthal (having a
      derivatizable functional group, -COOH, bonded directly to a phenyl group); and
      2,4-D, 2,4,5-T, dichlorprop, 2,4,5-TP, and 2,4-DB (having a derivatizable
      functional group, -COOH, bonded directly to a sp3 carbon atom)--was tested. The
      analytical method developed was proven successful for determining acidic
      herbicides, except for the dacthal diacid metabolite, in aqueous samples.

PMID- 17214996
TI  - A single loading dose of clopidogrel causes dose-dependent improvement of
      endothelial dysfunction in patients with stable coronary artery disease: results
      of a double-blind, randomized study.
AB  - Clinical studies have demonstrated beneficial effects for clopidogrel in patients
      with atherothrombotic disease. Recent in vitro studies identified stimulating
      effects of clopidogrel on endothelial cells, pointing towards mechanisms of
      action beyond the inhibition of platelet aggregation. We hypothesized that in
      vivo use of clopidogrel improves endothelial dysfunction in patients with
      coronary artery disease (CAD). Fifty-eight patients with CAD were randomly
      assigned to double-blinded oral administration of one single dose of clopidogrel
      300 mg (C300) or 600 mg (C600), respectively. Endothelial function was assessed
      by measurement of flow-mediated dilation (FMD) of the brachial artery before and
      2, 4 and 22 h after dose administration, respectively. Inhibition of the platelet
      ADP P2Y12 receptor by clopidogrel was monitored by the ex vivo analysis of ADP
      effects on prostaglandin-induced platelet VASP phosphorylation. C600
      significantly improved FMD at 2, 4 and 22 h, while C300 significantly improved
      FMD at 4 and 22 h. Clopidogrel dose- and time-dependently inhibited the platelet
      ADP P2Y12 receptor without correlation with its stimulatory effects on FMD. Our
      study demonstrates for the first time in vivo that clopidogrel dose-dependently
      improves endothelial dysfunction. These results may indicate a new and
      potentially important aspect of the effect of clopidogrel treatment in patients
      with CAD.

PMID- 17214998
TI  - The surface tension of a solid at the solid-vacuum interface, an evaluation from
      adsorption and wall potential calculations.
AB  - A method for the evaluation of quantities that are experimentally inaccessible
      such as the surface tension at the solid-vacuum interface and the superficial
      tension of the fluid in contact with the solid is presented. The approach is
      based on consideration of an equilibrium of a fluid in solid capillary wherein a
      balance between surface and capillary forces has been replaced by conceptual
      alternative interfacial and centrifugal forces. This approach involves the
      simultaneous numerical solution one the special forms of the Gibbs equation for
      solid-fluid interface and a generalized Kelvin equation derived earlier. The
      latter equation takes into account interactions between the solid thick
      cylindrical wall and confined fluid, this body-body interaction potential has
      been primarily calculated using the Lennard-Jones (6-12) expression for the atom
      atom pair potentials and expressed by hypergeometrical functions having good
      convergences. All numerical calculations shown here have been performed for the
      model graphite-argon system at 90 K. Finally, an analysis of the accuracy of the
      proposed method is considered.

PMID- 17214999
TI  - Diffusion of one or more components of a silane adhesion-promoting mixture into
      poly(methyl methacrylate).
AB  - The surface-sensitive technique of sum frequency generation (SFG) vibrational
      spectroscopy has been applied to study the buried interfaces between different
      polymers including deuterated polystyrene (d-PS) and deuterated poly(methyl
      methacrylate) (d-PMMA) and a two-component silane adhesion-promoting mixture
      (SAPM) composed of (3-glycidoxypropyl)trimethoxysilane (gamma-GPS) and a
      methylvinylsiloxanol (MVS). Because of the dissolution of d-PS, no SFG CH
      stretching signals could be collected from the d-PS/gamma-GPS interface, and SFG
      signals collected from the d-PS/SAPM interface gradually disappeared over time.
      SFG results also showed that gamma-GPS can diffuse through the d-PMMA film. The
      diffusion of gamma-GPS through the d-PMMA film was confirmed by SFG studies on
      the interface between gamma-GPS and a d-PMMA/PS two-polymer layer system.
      Initially the SFG signal from the PS layer was detected. However, after gamma-GPS
      diffused through the d-PMMA film, the PS film was dissolved by the silane, and
      thus the SFG signal from PS was lost. Similar experiments have been carried out
      at the interface between the SAPM and the d-PMMA/PS two-polymer layer system and
      it was found that the diffusion time of the gamma-GPS in the SAPM through the d
      PMMA film was significantly longer. These results were much different to those
      from previous SFG studies on the analogous PET interfaces and appear consistent
      with differences in solubility parameters calculated for these systems.

PMID- 17215000
TI  - Effect of ionic surfactants on bauxite residues suspensions viscosity.
AB  - Measurement of the rheological property of bauxite residue sample received from
      an Australian alumina refinery, treated with a number of cationic and anionic
      surfactant in laboratory has been carried out using a Brookfield viscometer for
      the assessment of the effect of surfactants on the residue viscosity. Sodium
      laurate, prepared with an excess of sodium hydroxide, was found to be effective
      while direct addition of anionic surfactants (lauric acid and sodium laureth
      sulphate) and cationic (cetyl trimethyl ammonium bromide) produce only moderate
      effect on the red mud suspension apparent viscosity at 65 degrees C. The
      experimental data appear to confirm the crucial role of the cation sodium in the
      process of adsorption of anionic surfactants on the flocculated red mud
      particles.

PMID- 17215001
TI  - Hydrothermal fabrication and characterization of polycrystalline linneite
      (Co(3)S(4)) nanotubes based on the Kirkendall effect.
AB  - In this study, polycrystalline linneite (Co(3)S(4)) nanotubes constructed with
      nanoparticles have been firstly fabricated using 1D
      Co(CO(3))(0.35)Cl(0.20)(OH)(1.10) nanowires as the sacrificial templates under
      hydrothermal conditions. The samples are characterized by means of XRD and TEM.
      The formation mechanism of the Co(3)S(4) nanotubes can be explained by the
      nanoscale Kirkendall effect, which results from the difference in diffusion rates
      between cobalt source and hydrogen sulfide. This simple synthetic route is
      expected to prepare other nanomaterials with the tubular structures.

PMID- 17215002
TI  - Transfer and distribution of L-tryptophan between W/O and O/W, and between W/O
      and bicontinuous microemulsions through the study of interphase electric
      properties.
AB  - The influence of L-tryptophan (L-Trp) on the interphase electric properties of
      sodium dodecyl sulfate (SDS)/n-pentanol (n-C(5)H(11)OH)/water (H(2)O) system was
      studied by the method of AC impedance, and the distribution of L-Trp between the
      microemulsion phases with different structures in SDS/n-C(5)H(11)OH/H(2)O system
      was determined by UV-vis spectroscopy. The results show that L-Trp transfers from
      the lower phase (O/W or bicontinuous) to the upper phase (W/O), and that a small
      amount of SDS transfers from the upper phase to the lower phase correspondingly
      with the increase of the total SDS content at a constant weight ratio of n
      C(5)H(11)OH/H(2)O=50/50 and a total L-Trp concentration of 1.0 x 10(-4) mol/L. In
      addition, the concentrations of L-Trp in both the upper and lower phases
      increase, but the SDS content decreases slightly in the upper phase and increases
      appreciably in the lower phase with the increase of the total L-Trp concentration
      at a constant total content of SDS. The interphase capacitance and the interphase
      charge-transfer current of the system increase, but the interphase resistivity
      decreases.

PMID- 17215003
TI  - Effects of different male remating intervals on the reproductive success of
      Choristoneura rosaceana males and females.
AB  - The mass of the spermatophore transferred by a previously mated Choristoneura
      rosaceana male increases with time elapsed since the last mating but, even after
      4 days, it never reaches the mass of the spermatophore of a virgin male. However,
      spermatophore mass is clearly not a good indicator of the male reproductive
      investment as the quantity of sperm in the second ejaculate of a previously mated
      male is the same as that of his first, if he is allowed a 2 (eupyrene sperm) to 3
      day (apyrene sperm) recovery period. The interval between the first two matings
      had no influence on female fecundity or longevity but significantly affected
      fertility if the male had only 1 day to recover. The length of the post
      copulatory refractory period was also shorter in females mated with previously
      mated males than in those mated with virgins, regardless of the male's remating
      interval. Furthermore, a significant variation in the eupyrene sperm content of
      the spermatophore transferred by virgin males had no influence on the length of
      the female refractory period. Globally, these results support the hypothesis that
      a factor, other than sperm numbers in the spermatheca, is responsible for
      maintaining the inhibition of pheromone production in this species.

PMID- 17215004
TI  - Motor inhibition in trichotillomania and obsessive-compulsive disorder.
AB  - We investigated motor inhibition abilities in trichotillomania (TTM) and
      obsessive-compulsive disorder (OCD), two disorders characterized by repetitive,
      intentionally performed behaviors. Performance in a GoNogo experiment of 25 TTM
      and 21 OCD participants was compared to the performance of 26 HC participants. In
      contrast to OCD and HC participants, TTM participants tended to perform either
      'fast and inaccurate' (indicating poor motor inhibition) or 'slow and accurate'.
      TTM participants with poor motor inhibition reported a significantly earlier age
      of TTM onset than those TTM participants who performed well. There was no
      evidence for motor inhibition deficits in OCD. Based on our data, a subgroup of
      TTM sufferers seems to be characterized by motor inhibition deficits.

PMID- 17215005
TI  - Activities of endogenous antioxidant enzymes in the cerebrospinal fluid and the
      hippocampus after transient forebrain ischemia in rat.
AB  - The activity of SOD and CAT was measured in controls and 5 h after 5, 10 and 15
      min of ischemia, as well as 1 or 2 days after 10 min of ischemia in the
      hippocampus and in the CSF. A significant increase in total SOD activity 5 h
      after ischemia was caused mainly by increased CuZn-SOD activity. The highest
      values were measured 5 h after 5 min ischemia (by 160%) and smallest if 15 min
      (by 40%) of ischemia was used. In comparison to the hippocampus, the activity of
      SOD in CSF increased equally after all intervals of ischemia. Activities of total
      SOD and CuZn-SOD after 10 min of ischemia in the hippocampus were significantly
      increased only after 5 and 24 h of reperfusion but in CSF they were increased
      after all examined intervals of reperfusion. The activity of CAT was
      significantly increased in the hippocampus after 5 (by 260%), 10 and 15 min (by
      100%) of ischemia. CAT activity in CSF was increased equally after all intervals
      of ischemia (by 200%). Ischemic attack causes a rapid response in hippocampal
      tissue as well as in the CSF, represented by an increase in the activity of
      endogenous antioxidant enzymes SOD and CAT.

PMID- 17215006
TI  - Reply to "Motor assessment of upper extremity function and its relation with
      fatigue, cognitive function and quality of life in multiple sclerosis patients".

PMID- 17215007
TI  - Spontaneous intrapetrous internal carotid artery dissection: a case report and
      literature review.
AB  - Although hemodynamic change has been identified as the main mechanism of infarcts
      in intracranial internal carotid artery dissection, no report has utilized
      computed tomography perfusion study to evaluate the cerebral flow change in such
      cases. This report presents a rare case of intrapetrous internal carotid artery
      dissection with watershed infarction. Additionally, a literature review addresses
      the clinical profiles and related neuroimaging findings of such patients.

PMID- 17215008
TI  - Absence of tissue-bound semicarbazide-sensitive amine oxidase activity in carp
      tissues.
AB  - We have previously reported that carp (Cyprinus carpio) tissue mitochondria
      contain a novel form of monoamine oxidase (MAO), which belongs neither to MAO-A
      nor to MAO-B of the mammalian enzyme. This conclusion results from the findings
      that the carp MAO was equally sensitive to a selective MAO-A inhibitor clorgyline
      and to the MAO-B selective inhibitor l-deprenyl, when tyramine, a substrate for
      both forms, serotonin or beta-phenylethylamine, a substrate for either A or B
      form of mammalian MAO, was used. In the present study, we tried to detect another
      amine oxidase, termed tissue-bound semicarbazide-sensitive amine oxidase (SSAO),
      activity in carp tissues. As definition of SSAO was used, such as insensitivity
      to inhibition of the kynuramine oxidizing activity by an MAO inhibitor pargyline
      and high sensitivity to the SSAO inhibitor semicarbazide. The results indicated
      that the oxidizing activity was selectively and almost completely inhibited by
      0.1 mM pargyline alone or a combination of 0.1 mM pargyline plus 0.1 mM
      semicarbazide, but not by 0.1 mM semicarbazide alone. We also tried to detect any
      SSAO activity by changing experimental conditions, such as lower incubation
      temperature, higher enzyme protein concentration, a lower substrate concentration
      and different pH's in the reaction, as the enzyme source. However, still no SSAO
      activity could be detected in the tissues. These results conclusively indicate
      that carp tissues so far examined do not contain SSAO activity.

PMID- 17215009
TI  - Altered expression profiles of clock genes hPer1 and hPer2 in peripheral blood
      mononuclear cells of cancer patients undergoing surgery.
AB  - Patients undergoing surgery often develop symptoms of circadian rhythm disorders
      such as insomnia or delirium. However, the effect of surgery on the biological
      clock remains unknown. The present study examines the expression of clock genes
      in peripheral blood mononuclear cells (PBMCs) and measures plasma hormone
      concentrations in patients with esophageal cancer and early gastric cancer who
      underwent surgery. Six blood samples per day were collected from 9 patients with
      esophageal cancer before and after esophagectomy and from 9 patients with early
      gastric cancer before and after laparoscopy-assisted distal gastrectomy (LADG).
      The expression profiles of hPer1 and hPer2 mRNAs in PBMCs were determined by real
      time RT-PCR. Plasma melatonin and cortisol concentrations were measured by
      radioimmunoassay. Plasma melatonin levels decreased in both groups throughout the
      day and plasma cortisol levels changed after surgery. The acrophase of clock gene
      expression was altered after surgery as follows: hPer1, from 6:19+/-1:50 to
      13:59+/-0:59 (p=0.0003) and from 7:47+/-1:27 to 12:33+/-1:30 (p=0.0043) and
      hPer2, from 5:01+/-2:59 to 19:30+/-2:15 (p<0.0001) and from 6:49+/-1:59 to
      13:39+/-3:06 (p=0.0171) in patients with esophageal and early gastric cancer,
      respectively. The post-operative phase change of hPer2 was more prominent after
      esophagectomy than after LADG. Our results suggest that surgical stress affects
      the peripheral clock as well as endogenous hormones in humans.

PMID- 17215010
TI  - Potential microbial bioinvasions via ships' ballast water, sediment, and biofilm.
AB  - A prominent vector of aquatic invasive species to coastal regions is the
      discharge of water, sediments, and biofilm from ships' ballast-water tanks.
      During eight years of studying ships arriving to the lower Chesapeake Bay, we
      developed an understanding of the mechanisms by which invasive microorganisms
      might arrive to the region via ships. Within a given ship, habitats included
      ballast water, unpumpable water and sediment (collectively known as residuals),
      and biofilms formed on internal surfaces of ballast-water tanks. We sampled 69
      vessels arriving from foreign and domestic ports, largely from Western Europe,
      the Mediterranean region, and the US East and Gulf coasts. All habitats contained
      bacteria and viruses. By extrapolating the measured concentration of a microbial
      metric to the estimated volume of ballast water, biofilm, or residual sediment
      and water within an average vessel, we calculated the potential total number of
      microorganisms contained by each habitat, thus creating a hierarchy of risk of
      delivery. The estimated concentration of microorganisms was greatest in ballast
      water>>sediment and water residuals>>biofilms. From these results, it is clear
      microorganisms may be transported within ships in a variety of ways. Using
      temperature tolerance as a measure of survivability and the temperature
      difference between ballast-water samples and the water into which the ballast
      water was discharged, we estimated 56% of microorganisms could survive in the
      lower Bay. Extrapolated delivery and survival of microorganisms to the Port of
      Hampton Roads in lower Chesapeake Bay shows on the order of 10(20) microorganisms
      (6.8 x 10(19) viruses and 3.9 x 10(18) bacteria cells) are discharged annually to
      the region.

PMID- 17215011
TI  - Inhibitors of phenylalanine ammonia-lyase: substituted derivatives of 2
      aminoindane-2-phosphonic acid and 1-aminobenzylphosphonic acid.
AB  - Six derivatives of 2-aminoindane-2-phosphonic acid and 1-aminobenzylphosphonic
      acid were synthesized. The compounds were tested both as inhibitors of buckwheat
      phenylalanine ammonia-lyase (in vitro) and as inhibitors of anthocyanin
      biosynthesis (in vivo). (+/-)-2-Amino-4-bromoindane-2-phosphonic acid was found
      to be the strongest inhibitor from investigated compounds. The results obtained
      are a basis for design of phenylalanine ammonia-lyase inhibitors useful in the
      enzyme structure studies in photo labelling experiments.

PMID- 17215012
TI  - Coverage, utilization and barriers to cataract surgical services in rural South
      India: results from a population-based study.
AB  - OBJECTIVES: To determine the cataract surgical coverage, utilization and barriers
      to cataract surgery in a rural taluk of south India. STUDY DESIGN: A cross
      sectional, community-based survey. METHODS: A house-to-house survey was carried
      out in 15 villages that were selected by cluster sampling during January to
      October, 2002. A total of 1505 people aged 50 years and above were tested for
      visual acuity (VA) and their eyes examined. Cataract surgical coverage was
      calculated for people and eyes, and for VA levels of <3/60 and <6/60. Information
      about details of cataract surgery and barriers to cataract surgery were collected
      using a pre-designed proforma. RESULTS: Cataract surgical coverage was 63%
      (people) and 51% (eyes) for VA<3/60 compared with 49% (people) and 36% (eyes) for
      VA<6/60. Of 109 operated eyes, 51.2% of operations were carried out in private
      hospitals and 33.3% in voluntary/charitable hospitals. Inability to afford the
      operation (22.9%) and fear of the operation (19.2%) were the main barriers to
      cataract surgery. CONCLUSIONS: The reasons for underutilization of government
      hospitals are to be investigated. Awareness of low-cost cataract intraocular lens
      (IOL) non-governmental organization (NGO) surgery and free-of-cost NGO services
      available in the region needs to be raised. Barriers to cataract surgical
      services should be addressed by community-based health-education programmes to
      improve the uptake of existing services.

PMID- 17215014
TI  - An in vivo examination of the stability of venom from the Australian box
      jellyfish Chironex fleckeri.
AB  - We have previously characterised the pharmacological activity of a number of
      jellyfish venoms with a particular emphasis on the profound cardiovascular
      effects. It has been suggested that jellyfish venoms are difficult to work with
      and are sensitive to pH, temperature and chemical changes. The current study
      aimed to examine the working parameters of the venom of the Australian box
      jellyfish Chironex fleckeri to enable fractionation and isolation of the toxins
      with cardiovascular activity. C. fleckeri venom was made up fresh each day and
      subjected to a number of different environments (i.e. a pH range of 5-9 and a
      temperature range of 4-30 degrees C). In addition, the effect of freeze drying
      and reconstituting the venom was investigated. Venom (50 microg/kg, i.v.)
      produced a transient hypertensive response followed by cardiovascular collapse in
      anaesthetised rats. This biphasic response was not significantly effected by
      preparation of the venom at a pH of 5, 7 or 9. Similarly, venom (50 microg/kg,
      i.v.) did not display a loss of activity when exposed to temperatures of 4, 20 or
      30 degrees C for 1.5h. However, the cardiovascular activity was abolished by
      boiling the venom. Freeze drying, and then reconstituting, the venom did not
      significantly affect its cardiovascular activity. However, repeated freeze drying
      and reconstituting of extracted venom resulted in a significantly loss of
      activity. This study provides a more detailed knowledge of the parameters in
      which C. fleckeri venom can be used and, while supporting some previous studies,
      contradicts some of the perceived problems of working with the venom.

PMID- 17215013
TI  - The differential preference of scorpion alpha-toxins for insect or mammalian
      sodium channels: implications for improved insect control.
AB  - Receptor site-3 on voltage-gated sodium channels is targeted by a variety of
      structurally distinct toxins from scorpions, sea anemones, and spiders whose
      typical action is the inhibition of sodium current inactivation. This site
      interacts allosterically with other topologically distinct receptors that bind
      alkaloids, lipophilic polyether toxins, pyrethroids, and site-4 scorpion toxins.
      These features suggest that design of insecticides with specificity for site-3
      might be rewarding due to the positive cooperativity with other toxins or
      insecticidal agents. Yet, despite the central role of scorpion alpha-toxins in
      envenomation and their vast use in the study of channel functions, molecular
      details on site-3 are scarce. Scorpion alpha-toxins vary greatly in preference
      for sodium channels of insects and mammals, and some of them are highly active on
      insects. This implies that despite its commonality, receptor site-3 varies on
      insect vs. mammalian channels, and that elucidation of these differences could
      potentially be exploited for manipulation of toxin preference. This review
      provides current perspectives on (i) the classification of scorpion alpha-toxins,
      (ii) their mode of interaction with sodium channels and pharmacological
      divergence, (iii) molecular details on their bioactive surfaces and differences
      associated with preference for channel subtypes, as well as (iv) a summary of the
      present knowledge about elements involved in constituting receptor site-3. These
      details, combined with the variations in allosteric interactions between site-3
      and the other receptor sites on insect and mammalian sodium channels, may be
      useful in new strategies of insect control and future design of anti-insect
      selective ligands.

PMID- 17215015
TI  - Novel porcine rotavirus of genotype P[27] shares new phylogenetic lineage with G2
      porcine rotavirus strain.
AB  - A novel and unusual strain of porcine rotavirus (PoRV) CMP034 was isolated from a
      7-week-old piglet during the epidemiological survey of porcine rotavirus
      infection in Chiang Mai province, Thailand from June 2000 to July 2001. Molecular
      characterization of gene VP4 by sequence analysis showed a low level of amino
      acid sequence identity, ranging from 56.7% to 76.6%, while comparison of VP8*
      portion showed 41.8% to 69.9% identity, with the 26 P genotypes recognized to
      date. Phylogenetic analysis of the VP4 sequence revealed that CMP034 was only
      distantly related to the other 26 P genotypes and was located in a separate
      branch. Sequence analysis of gene VP7 showed the highest level of amino acid
      identity (94.7%) with the PoRV G2-like reference strain 34461-4 but a lower level
      of identity with those of human G2 rotaviruses, ranging from 87.7% to 88.0%.
      Phylogenetic analysis of gene VP7 revealed two major lineages among G2 rotavirus
      strains based on the host origin. PoRV strain CMP034 clustered exclusively with
      G2-like PoRV strain 34461-4 in a novel lineage that is distinct from the major G2
      human lineage. Moreover, strain CMP034 displayed a porcine-like VP6 and NSP5/6
      with subgroup I specificity, while bearing an NSP4 with some genetic group B
      human-like characteristics. These findings provide evidence that CMP034 should be
      considered as a novel VP4 genotype P[27].

PMID- 17215016
TI  - Quantification of anaerobic ammonium-oxidizing bacteria in enrichment cultures by
      real-time PCR.
AB  - The anaerobic ammonium-oxidizing (ANAMMOX) bacteria were enriched from a rotating
      disk reactor (RDR) biofilm in semi-batch cultures. Based on fluorescence in situ
      hybridization (FISH) analysis, this enrichment led to a relative population size
      of 36% ANAMMOX bacteria. Phylogenetic analysis revealed that all the detected
      clones were related to the previously reported ANAMMOX bacteria, Candidatus
      Brocadia anammoxidans (AF375994), with 92% sequence similarity. Furthermore, we
      successfully developed a real-time polymerase chain reaction (PCR) assay to
      quantify populations of ANAMMOX bacteria in the enrichment cultures. For this
      real-time PCR assay, PCR primer sets targeting 16S ribosomal RNA genes of ANAMMOX
      bacteria were designed and used. The quantification range of this assay was 6
      orders of magnitude, from 8.9x10(1) to 8.9x10(6) copies per PCR, corresponding to
      the detection limit of 3.6x10(3) target copies mL(-1). A significant correlation
      was found between the increase in copy numbers of 16S rRNA gene of ANAMMOX
      bacteria and the increase in nitrogen removal rates in the enrichment cultures.
      Quantifying ANAMMOX bacterial populations in the enrichment culture made it
      possible to estimate the doubling time of the enriched ANAMMOX bacteria to be 3.6
      to 5.4 days. The real-time PCR assay gave comparable population sizes in the
      enrichment cultures with the FISH results. These results suggest that the real
      time PCR assay developed in this study is useful and reliable for quantifying the
      populations of ANAMMOX bacteria in environmental and engineering samples.

PMID- 17215017
TI  - High temporal resolution in situ measurement of the effective particle size
      characteristics of fluvial suspended sediment.
AB  - This paper reports the use of a LISST-100 device to monitor the effective
      particle size characteristics of suspended sediment in situ, and at a quasi
      continuous temporal resolution. The study site was located on the River Exe at
      Thorverton, Devon, UK. This device has not previously been utilized in studies of
      fluvial suspended sediment at the storm event scale, and existing studies of
      suspended sediment dynamics have not involved such a high temporal resolution for
      extended periods. An evaluation of the field performance of the instrument is
      presented, with respect to innovative data collection and analysis techniques. It
      was found that trends in the effective particle size distribution (EPSD) and
      degree of flocculation of suspended sediment at the study site were highly
      complex, and showed significant short-term variability that has not previously
      been documented in the fluvial environment. The collection of detailed records of
      EPSD facilitated interpretation of the dynamic evolution of the size
      characteristics of suspended sediment, in relation to its likely source and
      delivery and flocculation mechanisms. The influence of measurement frequency is
      considered in terms of its implications for future studies of the particle size
      of fluvial suspended sediment employing in situ data acquisition.

PMID- 17215018
TI  - Biomonitoring of PCDD/Fs in populations living near portuguese solid waste
      incinerators: levels in human milk.
AB  - In the context of two Environmental Health Surveillance Programs, launched in
      response to public and scientific concern in relation to waste incinerators
      located near Lisbon and in Madeira Island, two human biomonitoring projects have
      been started in Portugal, focussed in dioxins and dioxin-like compounds in human
      milk. Results from the undertaken studies have already provided data on the
      extent and pattern of dioxin body burden of both studied groups as well as a
      preliminary temporal trend of dioxin levels for the population residing near
      Lisbon incinerator. The present paper investigates difference between exposed and
      non-exposed subjects under study and, from a preventive perspective, possible
      covariates of the dioxin levels in human milk. Emissions from both incinerators
      appear to be well controlled as there is no increase of human body burden of
      dioxins as measured in human milk of individuals living near these facilities.
      Concerning other determinants of dioxin levels, results suggest confirmation of
      previously found significant age-dependent trend towards higher levels of dioxins
      in aged subjects. On the contrary, association between mother's levels of dioxins
      and parity lost significance. Apart from the issue of incineration, the general
      conclusion for the general population is that living in Lisbon as compared to
      Madeira results in higher milk dioxin levels and possible health risks. The
      profile of the single congeners for PCDD/Fs in human milk from Madeira and Lisbon
      shows similar contributions for 12378-PCDD, 23478-PCDF, 123678-HCDD and 2378
      TCDD, that account altogether for about 84% of the total identified dioxin body
      burden in the studied groups.

PMID- 17215019
TI  - POPs in the Lagoon of Venice: budgets and pathways.
AB  - Dioxins and furans (PCDD/Fs), polychlorobiphenyls (PCBs) and hexachlorobenzene
      (HCB) in the ecosystem of the Lagoon of Venice were studied, in order to provide
      a general picture of conditions in the lagoon in terms of contamination by
      persistent organic pollutants (POPs). We present here novel data on atmospheric
      deposition, water, sediment and clam samples collected in the lagoon during the
      period January 2001-December 2004. Atmospheric deposition was sampled monthly at
      six sites located both close and far from large industrial and urban sources.
      Water samples were collected monthly from fifteen stations, and twenty-five
      samples of sediments and clams (Tapes philippinarum) were collected in four areas
      where clams are farmed and harvested inside the lagoon. All samples were analysed
      for PCDD/Fs, PCBs and HCB by HRGC/HRMS in the same laboratory. All samples
      examined (atmospheric deposition and water) substantially confirmed the spatial
      pattern reported in previously published data on sediments and atmospheric
      deposition: the zone surrounding the Porto Marghera petrochemical plant always
      had the highest levels of POPs (i.e., PCDD/Fs: atmosphere approximately 6 pg of
      2,3,7,8-TCDD equivalents (I-TE) m(-2)d(-1); water 0.37 pg I-TEl(-1); sediment:
      300 ng kg(-1); clam 2.8 pg I-TE g(-1)), and the minima were found at points on
      the margins of the lagoon (PCDD/Fs: atmosphere approximately 1 pg I-TEm(-2)d(-1);
      water 0.05 pg I-TEl(-1); sediment: approximately 5 ng kg(-1); clam approximately
      0.2 pg I-TE g(-1)). Intermediate values were often encountered in the historical
      city centre of Venice and in the central part of the lagoon. To confirm this, new
      data on correlation between levels of PCDD/F in sediments and clams are reported,
      both for absolute values and for the PCDD/F "fingerprint". There is always a
      clear fingerprinting signature (PCDF/PCDD>1) for samples collected near Porto
      Marghera, and the opposite (PCDF/PCDD<1) in the rest of the lagoon.

PMID- 17215020
TI  - Methylsulfonyl PCB and DDE metabolites and their enantioselective gas
      chromatographic separation in human adipose tissues, seal blubber and pelican
      muscle.
AB  - In the present investigation, eleven human adipose tissue samples, two seal
      blubber samples and two pelican muscles samples were analyzed with regard to
      their concentrations of PCB parent compounds as well as to the respective chiral
      methylsulfonyl metabolites 3-MeSO2-CB 91, 4-MeSO2-CB 91, 3-MeSO2-CB 95, 4-MeSO2
      CB 95, 3-MeSO2-CB 149, 4-MeSO2-CB 149, 3-MeSO2-CB 132, 4-MeSO2-CB 132, 3-MeSO2-CB
      174, and 4-MeSO2-CB 174 and the achiral metabolites 3-MeSO2-CB 49, 4-MeSO2-CB 49,
      3-MeSO2-CB 101, 4-MeSO2-CB 101, 3-MeSO2-CB 110, 4-MeSO2-CB 110 and 3-MeSO2-DDE.
      In order to verify enantioselective transformation processes and to compare the
      different enzymatic transformation pathways in birds and mammals, the
      enantioselective excesses of the chiral PCB-metabolites were determined by
      enantioselective gas chromatography with electron capture and mass spectrometric
      detection using modified cyclodextrin phases, including heptakis(2,3-di-O-methyl
      6-O-tert-butyldimethylsilyl-)-beta-cyclodextrin/OV1701 (1:1) for the parent PCBs
      and heptakis(2,3-di-O-methyl-6-O-tert-butyldimethylsilyl-)-beta-cyclodextrin/SE52
      (1:4) for the metabolites, respectively.

PMID- 17215021
TI  - Polychlorinated dibenzothiophenes in Japanese environmental samples and their
      photodegradability and dioxin-like endocrine-disruption potential.
AB  - Polychlorinated dibenzothiophenes (PCDTs) in sediment, soil, and fly ash samples
      collected in Japan were analyzed and their dioxin-like endocrine-disruption
      potential and photodegradability investigated. PCDTs were detected in all three
      types of sample, although the concentrations were lower than those of
      polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans
      (PCDFs). An Ah-immunoassay confirmed that 2,3,7,8-TeCDT, 1,2,3,7,8-PeCDT,
      1,2,3,7,8,9-HxCDT, and 1,2,3,4,7,8,9-HpCDT had Ah receptor-binding activities,
      which means that these PCDTs have the potential to cause dioxin-like endocrine
      disruption. Photodegradation of PCDTs by UV irradiation was accompanied by
      dechlorination. The photodegradation rates of 2,3,7,8-TeCDT and OCDT were lower
      than the rates for the corresponding PCDF isomers (2,3,7,8-TeCDF and OCDF), which
      indicates that PCDTs are more stable than PCDFs to photodegradation.

PMID- 17215022
TI  - Arsenic speciation and accumulation in evapoconcentrating waters of agricultural
      evaporation basins.
AB  - To sustain agricultural productivity, evaporation basins (or ponds) have been
      widely used for the disposal of agricultural drainage in areas requiring
      subsurface drainage in the San Joaquin Valley of California, USA. The drainage
      water contains elevated concentration of trace elements including selenium (Se)
      and arsenic (As). Unlike Se, little information is available about As, a
      potentially high risk element. The objective of this study was to characterize
      the chemical behavior of As and acquire data for better understanding of
      biogeochemical processes and conditions affecting As fate in evaporation ponds.
      The study site was a 726 ha evaporation basin facility (containing 10 cells with
      water flowing in series) in the hydrologically closed Tulare Basin of California.
      We examined water chemistry, As concentration and speciation along the water flow
      path between cells as well as within the cells. Arsenic concentrations in the
      water increased linearly with Cl(-), a conservative ion from evapoconcentration.
      Reduced As species as arsenite [As(III)] and organic arsenic (org-As) also
      increased with increases in Cl(-) and salinity. Water samples with elevated EC
      (i.e., towards the end of flow path) had high dissolved organic matter, low
      dissolved oxygen, and elevated sulfide concentrations, indicating the development
      of reducing conditions. We hypothesize that such changes could facilitate the
      reduction of arsenate [As(V)] to As(III) and org-As. Elevated As in sediment
      profiles indicate a solid phase sink mechanism, but not significant enough to
      remove and reduce As concentrations in the water columns. These findings help us
      better define the processes that affect As in drainage facilities and contribute
      to our understanding of how As behaves in other regions of the world that have
      similar climatic and hydrogeochemical conditions.

PMID- 17215023
TI  - A simple spectrophotometric method for the determination of cobalt in industrial,
      environmental, biological and soil samples using
      bis(salicylaldehyde)orthophenylenediamine.
AB  - Bis(salicylaldehyde)orthophenylenediamine (BSOPD) has been proposed as new
      analytical reagent for the direct non-extractive spectrophotometric determination
      of cobalt. It reacts with cobalt in slightly acidic (0.0002-0.001 M H(2)SO(4))
      50% 1,4-dioxanic medium to form a red-orange chelate with a molar ratio 1:1. The
      reaction is instantaneous and the maximum absorbance was obtained at 458 nm and
      remains constant for over 24h. The average molar absorption coefficient and
      Sandell's sensitivity were found to be 1.109 x 10(4)l mol(-1)cm(-1) and 20 ng cm(
      2) of Co(II), respectively. Linear calibration graph was obtained for 0.1-15 mg
      l(-1) of Co(II) with a correlation coefficient value of 0.995 for Co-BSOPD
      complex. Large excess of 44 cations, anions and complexing agents do not
      interfere in the determination. The method was successfully used in the
      determination of cobalt(II) from synthetic mixture and certified reference
      materials for the purpose of validating the method and the results of analyses
      were found to be excellent agreement with those of actual values. This developed
      method was also used for determination of cobalt in some environmental waters
      (potable and polluted), biological (blood and urine) and soil samples and
      solution containing both cobalt(II) and cobalt(III). The results of the proposed
      method for biological samples were comparable with AAS and were found to be in
      good agreement. The method has high precision and accuracy (s=+/-0.01 for 0.5 mg
      l(-1)).

PMID- 17215024
TI  - Correlation of low-volatile organic chlorine (LVOCl) and PCDD/Fs in various
      municipal waste incinerators (MWIs).
AB  - Medium- and low-volatile organic chlorine (M/LVOCl) and PCDD/Fs in flue gas from
      various municipal waste incinerators (MWIs) were monitored. The sample for
      M/LVOCl was collected in an adsorption tube which was thermally desorbed and the
      amount of chlorine was measured by atomic emission spectrometry (AES) detection
      using radiofrequency helium plasma. The helium plasma excited chlorine having an
      optical emission line of 837.6 nm was monitored. The MVOCl and LVOCl were organic
      chlorine groups whose boiling points (bp) ranged from 70-120 degrees C and 170
      270 degrees C, respectively. The compounds having bp 120-170 degrees C were
      distributed in two tubes. LVOCl correlated well with PCDD/Fs (ng/Nm3, r=0.81) in
      a wide range of 0.01-100 ng/Nm3 of PCDD/Fs, while the correlation of LVOCl vs.
      TEQ was less related (r=0.69). These results agreed with the fact that LVOCl
      monitored the amount of organic chlorine without molecular structure information,
      which is critical to toxicity. Since the bp of LVOCl was not identical with that
      of PCDD/Fs, the regression was effected by the conditions of the gas treatment
      devices. Because most data of 2001 were collected just after the installation of
      PCDD/Fs in MWIs, the regression of 2001 was slightly different from that of 2002
      2003. Eliminating these initial unsteady data, the regression of LVOCl vs.
      PCDD/Fs became better, giving r= 0.86. Besides having PCDD/Fs as surrogates,
      M/LVOCl is valuable as a versatile element-selective organic chlorine monitor to
      improve thermal process control.

PMID- 17215025
TI  - A total diet study to estimate PCDD/Fs and dioxin-like PCBs intake from food in
      Taiwan.
AB  - Concentrations of 17 dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) and 12 dioxin-like
      polychlorinated biphenyls (dl-PCBs) were measured in total diet study samples of
      14 food groups of animal origin from 11 locations in Taiwan, collected in 2003.
      Pork meat possessed the lowest background concentration level of 0.058 pg WHO
      TEQ(PCDD/Fs+dl-PCBs)/g fresh weight. The dl-PCBs contribution were 31%, 59%, 36%,
      46%, and 13% for meat and meat products, muscle meat of fish, milk and dairy
      products, fat and oil, and egg, respectively. The estimated monthly intake (EMI)
      was 44.7 and 39.5 pg WHO-TEQ(PCDD/Fs+dl-PCBs)/kg b.w./month for a male and female
      adult weighing 64.8 kg and 56.3 kg, respectively. Muscle meat of fish contributes
      46% to the mean EMI. Factors affecting the EMI, in order of increasing importance
      are analytical method uncertainty, sample compositional difference, and food
      consumption data. In addition to the continuous efforts to identify and reduce
      the source of PCDD/Fs and dl-PCBs releases into the environment and the food
      chain, the practice of a healthy dietary habit, i.e., eating foods of lower TEQ
      levels, was suggested to effectively reduce human exposure to PCDD/Fs and dl
      PCBs.

PMID- 17215026
TI  - Simulating the temporal changes of OCP pollution in Hangzhou, China.
AB  - A dynamic fugacity model was applied to simulate the changes of contents and
      transfer fluxes of hexachlorocyclohexane (HCHs) and dichloro-diphenyl
      trichloroethane (DDTs) from 1950s in the environment of Hangzhou, China. The
      receptors are composed of air, surface water, soils, sediment and biota
      compartments. The model provides a method to combine loadings of HCHs and DDTs
      from various sources with a series of physical-chemical processes to estimate
      concentrations and transport fluxes of HCHs and DDTs. Model results suggested
      that the calculated concentrations were in line with the observed ones. The
      highest contents of HCH and DDT in the environment of study area were 523 t and
      471 t before 1983, among which about 80.7% HCHs and 93.2% DDTs remained in the
      soil compartment. From 1984 to now, contents of HCHs and DDTs had decreased to
      about 0.07% and 0.40% of their highest amount (before 1983), and only about
      0.001% and 0.014% will expect to be left in 2020 in the study area according to
      the model prediction. Before 1983, the main transfer fluxes of HCHs were
      deposition from air to soil, runoff from soil to water and diffusion from soil to
      air, but for DDTs the main transfer fluxes were deposition from air to soil and
      water, and transfer from water to sediment. From 1984 to now, runoff from soil to
      water and transfer from water to sediment became the dominant processes. Although
      a large amount of HCHs and DDTs had been applied to the study area, their residue
      levels in the soils were much lower than those in North China (had lesser HCHs
      and DDTs application than in South China) at present time, and close to other
      locations of South China (had similar HCHs and DDTs application level). It can be
      attributed to the high precipitation and temperature that enhances the processes
      of wet deposition, evaporation and degradation of OCPs. Sensitivities of the
      input parameters to the calculated concentrations were evaluated using
      coefficient-of-variation normalized sensitivity coefficients. The model was also
      subjected to uncertainty analyses using a Monte Carlo simulation.

PMID- 17215027
TI  - Physicochemical properties of selected polybrominated diphenyl ethers and
      extension of the UNIFAC model to brominated aromatic compounds.
AB  - The aqueous solubilities (S(w)) at various temperatures from 283 K to 308 K and 1
      octanol/water partition coefficients (K(ow)) for four polybrominated diphenyl
      ethers (PBDEs: 4,4'-dibromodiphenyl ether (BDE-15), 2,2',4,4'-tetrabromodiphenyl
      ether (BDE-47), 2,2',4,4',5-pentabromodiphenyl ether (BDE-99), and 2,2',4,4',5,5'
      hexabromodiphenyl ether (BDE-153)) were measured by the generator column method.
      The S(w) and K(ow) data revealed the effect of bromine substitution and basic
      structure on S(w) and K(ow). To estimate the infinite dilution activity
      coefficients (gamma(i)(w,infinity)) of the PBDEs in water from the S(w) data,
      enthalpies of fusion and melting points for those compounds were measured with a
      differential scanning calorimeter. Henry's Law constants (H(w)) of the PBDEs were
      derived from the determined gamma(i)(w,infinity) and literature vapor pressure
      data. Some physicochemical characteristics of PBDEs were also suggested by
      comparing the present property data with that of polychlorinated dibenzo-p
      dioxins, brominated phenols and brominated benzenes in past studies. Furthermore,
      in order to represent different phase equilibria including solubility and
      partition equilibrium for other brominated aromatic compounds using the UNIFAC
      model, a pair of UNIFAC group interaction parameters between the bromine and
      water group were determined from the S(w) and K(ow) data of PBDEs and brominated
      benzenes. The ability of the determined parameters to represent both properties
      of brominated aromatics was evaluated.

PMID- 17215028
TI  - Concentration and distribution of dioxins and related compounds in human tissues.
AB  - Polychlorinated dibenzo-p-dioxin, polychlorinated dibenzofuran and dioxin-like
      polychlorinated biphenyl concentrations in human blood, lung, liver, bile,
      pancreas, spleen, kidney and mesentery fat were determined to assess the
      concentrations and distribution of these chemicals in human tissues from 20
      donors. The mean TEQ concentrations in blood, lung, liver, bile, spleen,
      pancreas, kidney and mesentery fat were 119, 178, 228, 50, 113, 163, 138 and 139
      pg TEQ/g lipid, respectively. Parallel levels were seen in the blood, spleen,
      kidney and mesentery fat; in the lungs and pancreas, the levels were somewhat
      higher. Among the organ tissues samples, the highest concentration was observed
      in the liver and the lowest in the bile. Mean total-TEQ concentration of the
      liver was about 4.5 times higher than that of bile. Positive correlations were
      observed among the concentrations of dioxins in various tissues. However, the
      concentrations in bile were not correlated with any tissues. It is suggested that
      the distribution behavior of dioxin-like congeners in human tissues varies among
      tissues and the kinds of congeners ingested. To evaluate the relationship between
      the accumulation levels of dioxins and their pathophysiological significance or
      risk, data must be accumulated from a more extensive group of human samples.

PMID- 17215029
TI  - Mobilization and speciation of chromium in compost: a methodological approach.
AB  - An integral approach to study the mobility of chromium in compost is presented.
      The approach is based on batch pH dependence leaching tests and the analysis of
      the leachates for total chromium, chromium(VI) and complexes of chromium(III)
      with natural organic matter. As leachings are performed with no aggressive
      reagents (ultrapure water with added nitric acid or potassium hydroxide), the
      method can be considered a good approach to simulate natural scenarios. The
      analysis of leachates is complemented with the determination of total chromium
      and total Cr(VI) in the solid sample. Speciation analysis are done by high
      performance liquid chromatography with inductively coupled plasma mass
      spectrometry as detection technique; Cr(VI) is determined by ion chromatography,
      whereas Cr(III) complexes with natural organic matter by size exclusion
      chromatography. In the compost studied, Cr(VI) accounted for 6% of the total
      chromium in the solid, whereas no significant amounts of Cr(VI) were mobilized in
      the pH range studied (4-10). Chromium is mobilized as Cr(III) bound to organic
      matter, both to humic and fulvic acids, with an increasing contribution of humic
      acids at higher pHs.

PMID- 17215030
TI  - Plasma viscosity and related cardiovascular risk factors in a Spanish
      Mediterranean population.
AB  - INTRODUCTION: Plasma viscosity (PV) constitutes an independent important
      predictor of initial and recurrent cardiac events and mortality. It has been
      suggested that there is a geographical variation in PV values related to coronary
      event rates. Little information exists regarding PV in Spain. Therefore, our
      objective was to determine PV in a large sample of randomly selected subjects
      from the Spanish population and to study which demographic or cardiovascular risk
      factors (CVRF) influence levels of PV in this population. MATERIALS AND METHODS:
      1277 subjects (503 males, 774 females) aged 43+/-14 years (range: 20-70) were
      randomly selected from an Eastern Spanish population. These subjects were free of
      cardiovascular diseases and other major diseases. PV was measured at 37 degrees C
      by means of the Fresenius GmbH plasma viscosimeter. In addition, total
      cholesterol, triglycerides, glucose and fibrinogen were measured. RESULTS: In the
      crude analysis, no differences in PV were observed regarding gender (males:
      1.235+/-0.061 cP; females: 1.236+/-0.059 cP, P=0.952). Women older than 50 years
      showed higher PV:1.248+/-0.057 cP than those aged less than 50 years: 1.232+/
      0.059 cP, P=0.001. No differences in PV by age groups were observed in men
      (P=0.842). Furthermore, we evaluated the prevalence of the following CVRF:
      hypercholesterolemia, hypertriglyceridemia, hypertension, diabetes, tobacco
      smoking, obesity, and high fibrinogen levels. Prevalence of these factors was:
      28%, 4.3%, 8%, 2.3%, 33%, 8.8% and 15% respectively. As some of these CVRF were
      correlated with PV levels, we carried out a multivariate analysis to adjust PV
      levels for the potential confounding effect of each one of these factors. After
      multivariate adjustment, PV was positively associated with high fibrinogen (>320
      mg/dL) levels in both men and women (P<0.001). In addition, in women, but not in
      men, PV levels were independently associated with obesity (P<0.001) and
      hypertriglyceridemia (P=0.01). After the multivariate adjustment, the association
      between PV and age older than 50 in women did not remain statistically
      significant, revealing a confusing effect of the CVRF in the crude analysis.

PMID- 17215031
TI  - A cost-effectiveness analysis of chemotherapy for patients with recurrent
      platinum-sensitive epithelial ovarian cancer.
AB  - OBJECTIVE: The majority of patients with advanced epithelial ovarian cancer (EOC)
      will experience a recurrence after primary chemotherapy and receive second-line
      chemotherapy. Patients who have a disease-free interval >6 months (platinum
      sensitive) will often receive multiple chemotherapy regimens. Therefore, our goal
      was to assess the effectiveness and medical costs of chemotherapy for platinum
      sensitive patients with advanced EOC. METHODS: A decision analysis model compared
      several chemotherapeutic strategies in a hypothetical cohort of 10,000 platinum
      sensitive EOC patients with recurrent disease: (a) best supportive care (BSC);
      (b) second-line monotherapy; (c) second-line combination therapy; (d) third-line
      chemotherapy after disease progression on second-line monotherapy or combination
      therapy; (e) fourth-line chemotherapy after disease progression on second- and
      third-line chemotherapy. RESULTS: BSC and second-line therapies were cost
      effective strategies. The cost-effectiveness ratios ranged from $2896 for second
      line monotherapy to $4914 for fourth-line previous monotherapy. Compared to BSC,
      second-line monotherapy gained an additional 8 months of overall survival (OS)
      with a favorable incremental cost-effectiveness ratio (ICER) of $24,228 per life
      year saved (LYS). The ICER for second-line combination therapy compared to second
      line monotherapy was also favorable ($46,068 per LYS). Although third- and fourth
      line chemotherapy provided small improvements in OS, they were dominated by other
      strategies or had an unfavorable ICER (>$50,000 per LYS). CONCLUSIONS: Second
      line chemotherapy is cost-effective for patients with platinum-sensitive
      recurrent EOC. Due to minimal improvements in overall survival, third- and fourth
      line chemotherapy are not cost-effective strategies.

PMID- 17215032
TI  - Young patients with endometrial carcinoma selected for conservative treatment: a
      need for vigilance for synchronous ovarian carcinomas, case report and literature
      review.
AB  - BACKGROUND: The aim of this paper is to report a case of synchronous ovarian
      malignancy in a very young patient with early endometrial cancer who desired
      fertility-sparing management. CASE: Twenty one-year-old patient presented with an
      apparent early stage endometrial cancer and desiring conservative management.
      After failure of conservative management for 3 years, surgery was performed. An
      incidentally small papillary serous ovarian tumor of low malignant potential was
      found. CONCLUSION: Careful preoperative and intraoperative assessment of the
      adnexa is mandatory in young women with endometrial cancer. Those who desire
      ovarian preservation should be counseled regarding the high potential for
      coexisting ovarian malignancy.

PMID- 17215033
TI  - Incomplete digestion of codfish represents a risk factor for anaphylaxis in
      patients with allergy.
AB  - BACKGROUND: Fish represents one of the most important allergenic foods causing
      severe allergic reactions. Nevertheless, it has been shown that gastric digestion
      significantly reduces its allergenic capacity. OBJECTIVE: In this study, we
      assessed the absorption kinetics of fish proteins and investigated the clinical
      reactivity of patients with fish allergy to codfish digested at physiological or
      elevated gastric pH. METHODS: Healthy individuals were openly challenged with
      codfish and blood samples were evaluated by histamine release for absorbed fish
      allergens. Patients with allergy were recruited on the basis of previously
      diagnosed codfish allergy. Fish extracts were digested with gastric enzymes at pH
      2.0 and 3.0 and used for histamine release, skin prick tests, and titrated double
      blind placebo-controlled food challenges. RESULTS: Ingestion experiments in
      subjects without allergy revealed absorption of biologically active fish
      allergens only 10 minutes after ingestion with maximal serum levels after 1 to 2
      hours. Incubation of fish proteins with digestive enzymes at pH 2.0 resulted in a
      fragmentation of the proteins leading to a reduced biological activity evidenced
      by a significantly smaller wheal reaction and reduced histamine release. Fish
      digested at pH 3.0 revealed comparable reactivity patterns as undigested
      extracts. Moreover, these test materials triggered reactions at 10-fold to 30
      fold lower cumulated challenge doses in patients with allergy. CONCLUSION: Our
      data indicate the paramount importance of gastric digestion for fish allergens
      because the quantitatively significant absorption and elicitation of symptoms
      seemed to take place in the intestine. CLINICAL IMPLICATIONS: Hindered digestion
      puts patients with fish allergy at risk to develop severe allergic reactions at
      minute amounts of allergens.

PMID- 17215034
TI  - Fluorescent in situ hybridization for sex chromosome determination before and
      after fertilization in mice.
AB  - In mice, the relative numbers of male and female pups per litter not only can
      vary but can probably change over the course of pregnancy in response to numerous
      environmental and physiological factors. As such, a technique is required to
      determine gender at several developmental stages. Here we describe a robust and
      accurate fluorescent in situ hybridization (FISH) procedure for determining
      chromosomal sex that can be applied with minimal modification to sperm, pre-and
      post-implantation conceptuses and recovered dead post-natal pups. Sperm was
      prepared for FISH analysis y using a modified microwave decondensation
      denaturation technique. Preimplantation conceptuses (0.5dpc) were cultured to the
      morula stage before sexing. They were then acid-treated to remove the zona
      pellucida. Tissue homogenates from postimplantational conceptuses (8.5dpc) and
      stillborn pups were fixed to pre-etched slides. Specimens were hybridized with
      identical, commercially available DNA probes for the X (FITC) and Y (Cy3)
      chromosomes. Sperm ratios met the expected value of 0.5 when determined by using
      XY FISH. Preimplantation conceptuses pre-treated with pepsin yielded distinct
      fluorescence of X and Y chromosomes in morulae, whereas microwave decondensation
      resulted in loss of conceptuses from the slide. Both 4.0 and 8.5dpc conceptuses
      displayed mean sex ratios of 0.5. Post-natal FISH analysis allowed gender
      identification of pups that could not be sexed due to developmental abnormalities
      or partial cannibalism. FISH analysis of sperm and of multiple conceptuses or
      post-natal tissue provided a cost-effective, accurate alternative to PCR-based
      sex determination.

PMID- 17215035
TI  - Bonding to ground versus unground enamel in fluorosed teeth.
AB  - OBJECTIVES: To determine the effect of grinding on the bonding effectiveness of a
      self-etch and an etch-and-rinse adhesive to fluorosed enamel. METHODS: The teeth
      were classified using the Thylstrup and Fejerskov index (TFI). Fluorosed teeth
      (TFI=5) obtained from Isparta (Turkey) and control teeth (TFI=0) obtained from
      Leuven (Belgium) were used. Using a depth-marking diamond bur, 0.3mm of enamel
      was removed from mid-buccal and mid-palatal/lingual surfaces of the teeth,
      whereas the area adjacent to the ground area was left unprepared. A two-step self
      etch (Clearfil Protect Bond, Kuraray) and a three-step etch-and-rinse adhesive
      (Optibond FL, Kerr) were used to bond the resin composite to the ground and
      unground enamel. Rectangular micro-specimens were prepared using the slow-speed
      diamond saw and tested in tensile to determine the micro-tensile bond strength
      (microTBS). RESULTS: The microTBS to unground fluorosed enamel was significantly
      lower than to ground fluorosed enamel for Clearfil Protect Bond (15.8+/-15.2 and
      45.0+/-12.4MPa, p<0.0001) and for Optibond FL (35.5+/-21.4 and 50.5+/-12.3MPa,
      p<0.05), respectively. In control teeth, Clearfil Protect Bond bonded better to
      ground enamel (p<0.01), whereas OptiBond FL exhibited a similar bonding
      effectiveness to ground and unground enamel (p=0.0634). SIGNIFICANCE: Preparation
      of enamel improved the resin-enamel bond strength in fluorosed teeth. The bonding
      effectiveness to unground enamel was lower in fluorosed teeth than in control
      teeth for the self-etch adhesive tested.

PMID- 17215036
TI  - The effect of food simulants on porcelain-composite bonding.
AB  - PURPOSE: The purpose of this study was to evaluate the in vitro effects of food
      simulants on the bond strength of brackets to porcelain surfaces. MATERIALS AND
      METHODS: One hundred and eighty porcelain-fused to metal specimens were
      fabricated. Samples were divided into 3 groups including 60 specimens each.
      Different surface treatment methods were applied to each group and these were:
      sandblasting (SB), etching with orthophosphoric acid (OPA) and etching with
      hydrofluoric acid (HFA). After the surface treatments, the brackets were bonded
      to the center of each sample with a light-curing orthodontic composite adhesive.
      Then each group was divided into five test subgroups and one control subgroup
      each consisting of 10 specimens. The test groups were conditioned for 90 days at
      37 degrees C as follows: water, 0.02N citric acid, heptane, 8% ethanol aqueous
      solution and 50% ethanol aqueous solution. The control specimens were stored at
      room temperature in air. Shear force was applied to the porcelain-bracket
      interface by using a universal testing machine with a crosshead speed of 1 mm/min
      until debonding occurred. The shear bond strength was calculated by dividing the
      maximum load by the cross-sectional area of the bracket to give the results in
      megapascals (MPa). The statistical evaluations were made by using analysis of
      variance. Whenever a significance was detected, Bonferroni tests were performed
      for post hoc analyses. RESULTS: Fifty percent ethanol conditioned specimens for
      all surface treatment groups showed lower shear bond strength values. HFA group
      showed significantly higher shear bond strength values when compared with other
      groups (P < 0.05). For all porcelain surface treatment groups, control groups
      showed statistically significant higher shear bond strength values (P < 0.05).
      CONCLUSION: The results of this in vitro study show that food simulants
      significantly decrease the bond strength between bracket and porcelain surface.

PMID- 17215037
TI  - Temporal and spatially controllable cell encapsulation using a water-soluble
      phospholipid polymer with phenylboronic acid moiety.
AB  - Temporal and spatially controllable cell encapsulation based on a water-soluble
      phospholipid polymer is reported in this study. Phospholipid polymers, i.e.,
      poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p
      vinylphenylboronic acid) (PMBV), were synthesized. A series of hydrogels was
      prepared between the water-soluble PMBV and other water-soluble polymers having
      multi-valent alcoholic groups, such as poly(vinyl alcohol) (PVA). The PMBV/PVA
      hydrogels were formed not only in water, but also in a cell culture medium, and
      dissociated by the excess addition of low molecular weight di-valent hydroxyl
      compounds, such as d-glucose. The PMBV/PVA hydrogel was applied as a cell
      container which has three-dimensional matrices for the reversible encapsulation
      of living cells without any response in it. Uniform cell seeding can be achieved
      using the hydrogels due to the homogenous gel formation of PMBV and PVA in the
      cell culture medium. Fibroblast cells were encapsulated in the PMBV/PVA hydrogel
      and maintained for 1 week. After dissociation of the PMBV/PVA hydrogel, the cells
      were seeded on conventional tissue culture polystyrene. The cells adhered and
      proliferated as usual on the plate. That is, the PMBV/PVA hydrogel will be useful
      as a cell-container, which can maintain the cells without any significant adverse
      effect on the entrapped cells.

PMID- 17215038
TI  - The effect of substratum topography on osteoblast adhesion mediated signal
      transduction and phosphorylation.
AB  - Substratum surface topography is a powerful modulator of cell behaviour, but how
      it influences intracellular signaling is largely unknown. We investigated the
      influence of microfabricated topographies on the activation of nonreceptor
      tyrosine kinases Src, FAK and ERK 1/2, as well as the transcription factor,
      Runx2, in rat osteoblasts, cultured on substrata that varied in their ability to
      promote bone-like tissue formation. Total tyrosine phosphorylation increased on
      grooves, tapered pits, and gap cornered boxes, relative to the levels found on
      smooth surfaces, with the greatest activity at 1 week. Src levels was higher on
      smooth than on any other surface, but FAK and ERK 1/2 phosphorylation were
      highest on groove and gap-cornered boxes up to 6 weeks. Inhibition of Src
      phosphorylation with PP2 inhibited FAK and ERK 1/2 phosphorylation on grooves,
      but had no detectable effect on either FAK or ERK 1/2 on smooth substratum. We
      suggest that osteoblast response to substrata with specific topographical
      features requires FAK-Y397-Src-Y416 complexes for ERK 1/2 phosphorylation, but on
      smooth surfaces, Src independent methods of ERK 1/2 activation are present.

PMID- 17215040
TI  - Development of plasmid vector and electroporation condition for gene transfer in
      sporogenic lactic acid bacterium, Bacillus coagulans.
AB  - Bacillus coagulans is a sporogenic lactic acid bacterium that ferments glucose
      and xylose, major components of plant biomass, a potential feedstock for
      cellulosic ethanol. The temperature and pH for optimum rate of growth of B.
      coagulans (50 to 55 degrees C, pH 5.0) are very similar to that of commercially
      developed fungal cellulases (50 degrees C; pH 4.8). Due to this match,
      simultaneous saccharification and fermentation (SSF) of cellulose to products by
      B. coagulans is expected to require less cellulase than needed if the SSF is
      conducted at a sub-optimal temperature, such as 30 degrees C, the optimum for
      yeast, the main biocatalyst used by the ethanol industry. To fully exploit B.
      coagulans as a platform organism, we have developed an electroporation method to
      transfer plasmid DNA into this genetically recalcitrant bacterium. We also
      constructed a B. coagulans/E. coli shuttle vector, plasmid pMSR10 that contains
      the rep region from a native plasmid (pMSR0) present in B. coagulans strain P4
      102B. The native plasmid, pMSR0 (6823bp), has 9 ORFs, and replicates by rolling
      circle mode of replication. Plasmid pNW33N, developed for Geobacillus
      stearothermophilus, was also transformed into this host and stably maintained
      while several other Bacillus/Escherichia coli shuttle vector plasmids were not
      transformed into B. coagulans. The transformation efficiency of B. coagulans
      strain P4-102B using the plasmids pNW33N or pMSR10 was about 1.5x10(16) per mole
      of DNA. The availability of shuttle vectors and an electroporation method is
      expected to aid in genetic and metabolic engineering of B. coagulans.

PMID- 17215039
TI  - Child multi-type maltreatment and associated depression and PTSD symptoms: the
      role of social support and stress.
AB  - OBJECTIVE: This retrospective, cross-sectional study explored the hypothesis that
      multiple forms of child abuse and neglect (child multi-type maltreatment; CMM)
      would be associated with women's lower social support and higher stress in
      adulthood, and that this, in turn, would amplify their vulnerability to symptoms
      of depression and posttraumatic stress disorder (PTSD). METHOD: Participants were
      100 women recruited from an inner-city gynecological treatment center for low
      income women. Data were analyzed via structural equation modeling (SEM) with
      Lisrel 8.0. RESULTS: CMM was directly predictive of decreased social support and
      increased stress in adulthood. CMM was also directly predictive of PTSD symptoms,
      but not depression symptoms in adulthood. Social support partially mediated the
      relationship between CMM and adult PTSD symptoms, and stress fully mediated the
      relationship between CMM and adult symptoms of depression. CONCLUSIONS: Findings
      support both direct and mediational effects of social resources on adult
      depression and PTSD symptoms in women with histories of CMM, suggesting that
      resources are key factors in psychological adjustment of CMM victims.

PMID- 17215041
TI  - Honeybee Apis mellifera acetylcholinesterase--a biomarker to detect deltamethrin
      exposure.
AB  - The purpose of this study is to investigate the possibility to use
      acetylcholinesterase (AChE) as a biomarker of exposure to deltamethrin
      insecticide in the honeybee, Apis mellifera and to test its reliability in the
      presence of other contaminants, as carbamate insecticide. Joined actions of
      deltamethrin (pyrethroid) and pirimicarb (carbamate), alone or in association,
      are investigated on AChE activity in surviving and dead honeybees, with a special
      focus on the relative proportions of its membrane and soluble forms. At the 0.5X
      dose (12.5 ng of deltamethrin and/or 2.5 microg of pirimicarb per bee), the
      residual tissue AChE activity in dead bees was 78% with deltamethrin, 43% with
      pirimicarb and 33% with dual treatment. In surviving bees, tissue AChE activity
      represented 250%, and 270% of control AChE activity with deltamethrin and dual
      treatment, respectively. The analysis of membrane and soluble AChE forms revealed
      an increase in the soluble form in dead bees after deltamethrin and dual
      treatment. However, in vitro investigations showed no direct interaction of
      deltamethrin on soluble and membrane AChE activity. The results suggest that the
      action of deltamethrin on AChE activity, in honeybee intact organisms, could be
      due to indirect mechanisms. The duality of AChE response to deltamethrin
      exposure, exhibited by the possibility of increase (surviving bees) or decrease
      (dead bees) of its activity has been pointed out for the first time. The
      important increase in AChE activity in response to deltamethrin, not altered by
      pirimicarb treatment, suggests that AChE activity could represent a robust
      biomarker specific to deltamethrin exposure in living bees.

PMID- 17215043
TI  - Lysosomal responses and metallothionein induction in the blue mussel Mytilus
      edulis from the south-west coast of Iceland.
AB  - It has recently been emphasized that high levels of inorganic and organic
      micropollutants (particularly organometals, POPs and PAHs) may be present in
      coastal waters at high latitudes, stressing the need to evaluate the effects of
      contaminants on marine organisms from sub-arctic zones. With this aim, specimens
      of the blue mussel Mytilus edulis were sampled in polluted and reference areas
      along the south-west coast of Iceland in July 2004. Samples were collected from
      the intertidal zone at three sites in Reykjavik harbour which are differently
      exposed to contaminants, and at three reference coastal sites, two located along
      the Reykjanes Peninsula and the third one on the northern part of Hvalfjordur
      fiord. Lipofuscin content, neutral lipid accumulation and lysosomal enlargement
      were evaluated in digestive cells from cryostat sections of the mussel
      hepatopancreas, and quantified by automated image analysis. Metallothionein
      induction was also determined in the same tissue. Results indicate that mussels
      from the inner part of Reykjavik harbour, which is the most sheltered and most
      influenced by extensive shipping traffic, were the worst affected, with the
      highest values in neutral lipids, lipofuscin and lysosomal swelling. At the other
      two harbour sites, mussels exhibited lower values, similar to those observed in
      organisms collected in Hvalfjordur fiord and in bay of Osar. Mussels from
      Kuagerdi had the lowest values.

PMID- 17215042
TI  - Clinical delineation of fetal alcohol spectrum disorders (FASD) in Italian
      children: comparison and contrast with other racial/ethnic groups and
      implications for diagnosis and prevention.
AB  - In Italy, little is known about the spectrum of adverse fetal effects related to
      maternal alcohol use during pregnancy. In this paper, we report on the phenotype
      of Italian children with fetal alcohol spectrum disorders (FASD). These data were
      gathered as part of a field study assessing the prevalence of FASD in children in
      an in-school study in a rural area near Rome. The purposes of this paper are: (1)
      to completely characterize the clinical phenotype of a large cohort of Italian
      children with FASD; (2) to correlate and contrast the phenotype of this
      population with that observed in other populations and reported in the medical
      literature; (3) to discuss the drinking habits of Italian women, before, during
      and after pregnancy; and (4) to suggest mechanisms for intervention and
      prevention of FASD based on data gathered from this study.

PMID- 17215044
TI  - The copper(II) coordination abilities of three novel cyclic tetrapeptides with 
      His-Xaa-His- motif.
AB  - Three novel cyclic tetrapeptides, containing either l- or d-histidine residues
      and either Lys or Asp side chains, namely c(HGd-HK) (1), cHGHD (2) and c(HGd-HD)
      (3), were designed, synthesized, characterized and tested as potential copper(II)
      ligands. Their pH dependent copper(II) binding properties were analysed in depth
      by a number of potentiometric and spectroscopic determinations. A rather
      exhaustive description of the species existing in solution has emerged for each
      copper(II)/oligopeptide system; solution structures for the individual species
      are proposed. The specific role of the various side chains in the overall metal
      coordination process is discussed in comparison with the case of Cu(II)-c(HGHK),
      previously reported. Data obtained in this study highlight the strong impact of
      the d-His residue on the metal binding abilities of these cyclic peptides.
      Remarkably, the cyclic tetrapeptides containing two l-His residues are able to
      form, at physiologically relevant pH values, a characteristic chromophore where
      the mononuclear copper(II) centre is simultaneously coordinated by two imidazole
      nitrogens and two amidic nitrogens of the tetrazadodecane ring. This latter type
      of copper(II) chromophore has been carefully modelled by computational methods.
      The potentialities of the applied experimental strategy are stressed.

PMID- 17215045
TI  - UK malaria treatment guidelines.
AB  - Malaria is the tropical disease most commonly imported into the UK, with 1500
      2000 cases reported each year, and 10-20 deaths. Approximately three-quarters of
      reported malaria cases in the UK are caused by Plasmodium falciparum, which is
      capable of invading a high proportion of red blood cells and rapidly leading to
      severe or life-threatening multi-organ disease. Most non-falciparum malaria cases
      are caused by Plasmodium vivax; a few cases are caused by the other two species
      of Plasmodium: Plasmodium ovale or Plasmodium malariae. Mixed infections with
      more than 1 species of parasite can occur; they commonly involve P. falciparum
      with the attendant risks of severe malaria. Management of malaria depends on
      awareness of the diagnosis and on performing the correct diagnostic tests: the
      diagnosis cannot be excluded until 3 blood specimens have been examined by an
      experienced microscopist. There are no typical clinical features of malaria, even
      fever is not invariably present. The optimum diagnostic procedure is examination
      of thick and thin blood films by an expert to detect and speciate the malarial
      parasites; P. falciparum malaria can be diagnosed almost as accurately using
      rapid diagnostic tests (RDTs) which detect plasmodial antigens or enzymes,
      although RDTs for other Plasmodium species are not as reliable. The treatment of
      choice for non-falciparum malaria is a 3-day course of oral chloroquine, to which
      only a limited proportion of P. vivax strains have gained resistance. Dormant
      parasites (hypnozoites) persist in the liver after treatment of P. vivax or P.
      ovale infection: the only currently effective drug for eradication of hypnozoites
      is primaquine. This must be avoided or given with caution under expert
      supervision in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD),
      in whom it may cause severe haemolysis. Uncomplicated P. falciparum malaria can
      be treated orally with quinine, atovaquone plus proguanil (Malarone) or co
      artemether (Riamet); quinine is highly effective but poorly tolerated in
      prolonged dosage and is always supplemented by additional treatment, usually with
      oral doxycycline. ALL patients treated for P. falciparum malaria should be
      admitted to hospital for at least 24 h, since patients can deteriorate suddenly,
      especially early in the course of treatment. Severe falciparum malaria, or
      infections complicated by a relatively high parasite count (more than 2% of red
      blood cells parasitized), should be treated with intravenous therapy until the
      patient is well enough to continue with oral treatment. In the UK, the treatment
      of choice for severe or complicated malaria is currently an infusion of
      intravenous quinine. This may exacerbate hypoglycaemia that can occur in malaria;
      patients treated with intravenous quinine therefore require careful monitoring.
      Intravenous artesunate reduces high parasite loads more rapidly than quinine and
      is more effective in treating severe malaria in selected situations. It can also
      be used in patients with contra-indications to quinine. Intravenous artesunate is
      unlicensed in the EU. Assistance in obtaining artesunate may be sought from
      specialist tropical medicine centres, on consultation, for named patients.
      Patients with severe or complicated malaria should be managed in a high
      dependency or intensive care environment. They may require haemodynamic support
      and management of acute respiratory distress syndrome, disseminated intravascular
      coagulation, renal impairment/failure, seizures, and severe intercurrent
      infections including gram-negative bacteraemia/septicaemia. Falciparum malaria in
      pregnancy is more likely to be severe and complicated: the placenta contains high
      levels of parasites. Stillbirth or early delivery may occur and diagnosis can be
      difficult if parasites are concentrated in the placenta and scanty in the blood.
      The treatment of choice for falciparum malaria in pregnancy is quinine;
      doxycycline is contraindicated in pregnancy but clindamycin can be substituted
      for it, and is equally effective. Primaquine (for eradication of P. vivax or P.
      ovale hypnozoites) is contraindicated in pregnancy; after treatment for these
      infections a pregnant woman should take weekly chloroquine prophylaxis until
      after delivery when hypnozoite eradication can be considered. Children are over
      represented in the incidence of malaria in the UK, probably because completely
      susceptible UK-born children accompany their overseas-born parents on visits to
      family and friends in endemic areas. Malaria in children (and sometimes in
      adults) may present with misleading symptoms such as gastrointestinal features,
      sore throat or lower respiratory complaints; the diagnosis must always be sought
      in a feverish or very sick child who has visited malaria-endemic areas. Children
      can be treated with most of the antimalarial regimens which are effective in
      adults, with appropriate dosage adjustment. Doxycycline plus quinine should not
      be given to children under 12 years as doxycycline is contraindicated in this age
      group, but clindamycin can be substituted for doxycycline, and pyrimethamine
      sulfadoxine (Fansidar) may also be an effective substitute. An acute attack of
      malaria does not confer protection from future attacks: individuals who have had
      malaria should take effective anti-mosquito precautions and chemoprophylaxis
      during future visits to endemic areas.

PMID- 17215046
TI  - Repetitive Transcranial Magnetic Stimulation (rTMS) in the treatment of panic
      disorder (PD) with comorbid major depression.
AB  - BACKGROUND: Studies suggest that the dorsolateral prefrontal cortex (DLPFC)
      participates in neural circuitry that is dysregulated in Panic Disorder (PD) and
      Major Depressive Disorder (MDD). We tested whether low-frequency repetitive
      Transcranial Magnetic Stimulation (rTMS) could normalize the overactivity of
      right frontal regions and thereby improve symptoms. METHODS: Six patients with PD
      and comorbid MDD were treated with daily active 1-Hz rTMS to the right DLPFC for
      2 weeks in this open-label trial. RESULTS: Clinical improvements were apparent as
      early as the first week of treatment. After the second week, 5/6 of patients
      showed improvements in panic and anxiety, and 4/6 showed a decrease in
      depression, with sustained improvement at 6 months of follow-up. Right hemisphere
      resting motor threshold increased significantly after rTMS. LIMITATIONS:
      Limitations of this study are the open design and the small sample size.
      CONCLUSIONS: Slow rTMS to the right DLPFC resulted in significant clinical
      improvement and reduction of ipsilateral motor cortex excitability. Replications
      in larger sample will help to clarify the relevance of this preliminary data and
      to define the potential role of right DLPFC rTMS in panic with major depression.

PMID- 17215047
TI  - Proinflammatory cytokine mRNA expression in mammary tissue of sows following
      intramammary inoculation with Escherichia coli.
AB  - The expression of the proinflammatory cytokines interleukin-1beta (IL-1beta), IL
      6, IL-8, and tumor necrosis factor-alpha (TNF-alpha) mRNAs was determined by
      reverse transcription-PCR (RT-PCR) analysis of biopsies from the mammary glands
      of sows. The biopsies were collected before and 24h after intramammary
      inoculation of 12 pregnant sows with Escherichia coli (E. coli). Four of the sows
      developed clinical signs of mastitis and these animals displayed significantly
      lower levels of IL-1beta mRNA before inoculation than those that remained
      clinically healthy. There was a significant increase in IL-1beta, IL-6, IL-8, and
      TNF-alpha mRNA expression in the inoculated mammary glands of sows that developed
      clinical signs of mastitis (affected group) 24h postinoculation. This was also
      true for IL-8 and TNF-alpha mRNA expression in the inoculated mammary glands of
      sows that did not develop clinical signs of mastitis (non-affected group). No
      significant differences were found in IL-1beta, IL-6, and TNF-alpha mRNA
      expression in the inoculated mammary glands between groups (affected versus non
      affected) 24h postinoculation. Thus, a local production of proinflammatory
      cytokines in the mammary gland of sows was indicated by the induced expression of
      IL-1beta, IL-6, IL-8, and TNF-alpha mRNAs after intramammary inoculation with E.
      coli.

PMID- 17215048
TI  - T7 phage display of Ep15 peptide for the detection of WNV IgG.
AB  - West Nile virus (WNV) is one of the major emerging infectious diseases in North
      America. WNV belongs to the genus Flavivirus, and its rapid and extensive global
      spread has highlighted the necessity for accurate and specific assays for
      diagnosis of WNV infection. This study presents the first phage displayed peptide
      based ELISA for detection of WNV immunoglobulin G (IgG). The Ep15 epitope,
      derived from the WNV E protein DIII, was cloned into a T7 phage display system
      that was then used as recombinant antigen in a chemiluminescent ELISA format. The
      phage concentration was optimized at 5 x 10(10)PFU/ml and was used directly after
      polyethylene glycol concentration. The assay shows a limit of detection at a
      serum titer of 1:51,200 and a dynamic range from 1:100 to 1:2000. A screen of a
      panel of 66 human sera samples, and comparison with a commercial kit, revealed a
      sensitivity of 67% and a specificity of 100%. Considering the ease of antigen
      preparation, its stability and the optimum display properties of the T7
      bacteriophage, it is apparent that this approach can be useful for the
      preparation of highly sensitive and specific anti-WNV immunoglobulin diagnostic
      kits.

PMID- 17215049
TI  - Herpes glycoprotein gL is distantly related to chemokine receptor ligands.
AB  - Glycoprotein L (gL) is one of the critical proteins involved in transmission of
      Herpesviridae. We applied the methodology of protein structure prediction to shed
      a light on the so far unknown molecular mechanism of its action. Here we show
      that gL forms a chemokine-like protein. Alphaherpesvirinae gL as well as CMV
      functional homolog (UL130) create a novel CX chemokine-like protein, while
      Gammaherpesvirinae gL (HHV8 and EBV) adopt a regular CC beta-chemokine fold. We
      conclude that gL may interact with specific cellular chemokine receptors during
      the invasion of Herpesviridae. The proposed mechanism has a potential impact on
      future development of novel therapeutic and prophylactic strategies.

PMID- 17215050
TI  - SeqHepB: a sequence analysis program and relational database system for chronic
      hepatitis B.
AB  - SeqHepB is a combination of a HBV genome sequence analysis program and a
      relational database that houses data collected from multiple data sources.
      Registered users can access the sequence analysis component of SeqHepB online for
      rapid and detailed interrogation of HBV genomic sequences. Its main function is
      to determine the HBV genotype, identify key mutations associated with antiviral
      resistance, and identify clinically important HBV mutants. All information
      generated is uploaded into a database and integrated with patient medical
      records, pathology laboratory tests, and supplemental virology results such as in
      vitro drug cross-resistance values. Combined with structured query language (SQL)
      queries developed in the database, it is possible to extract and correlate
      clinical, virological, and in vitro phenotypic data rapidly and efficiently. An
      important component of SeqHepB is its ability to integrate mutations detected
      within the reverse transcriptase (RT) and locate them onto a three-dimensional
      (3D) model of the HBV RT that can be viewed at any angle with known antiviral
      drug molecules in the catalytic pocket of the enzyme. SeqHepB will enable
      virologists and physicians to individualise patient management, cope with the
      explosion of antiviral associated HBV mutations, and to conduct cross-sectional
      retrospective or prospective studies on HBV-infected individuals during therapy.

PMID- 17215051
TI  - Asymmetrical participation of the left and right hippocampus for representing
      environmental geometry in homing pigeons.
AB  - Control, right and left HF lesioned homing pigeons (Columba livia) were trained
      to locate a goal in one corner of a rectangular enclosure with a distinctive
      feature cue. Probe tests revealed that all groups were able to encode in parallel
      geometric (enclosure shape) and feature information, and in the absence of one of
      them, they could us the other to locate the goal. However, left HF lesioned
      pigeons learned the task at a faster rate, and when the geometric and feature
      information were set in conflict, they relied more on the feature cue compared to
      control and right HF lesioned pigeons. It was also found that pigeons,
      independent of group, trained to a goal adjacent to the feature cue learned the
      task in fewer sessions and relied more on feature information compared to pigeons
      trained to a goal opposite the feature cue. The latter group relied more on
      geometric information. The results support the hypothesis that the left HF plays
      a more important role in the representation of a goal location with respect to
      environmental shape/geometry. We further propose that the observed functional
      asymmetry can be explained by the lateralized properties of the pigeon tectofugal
      visual system.

PMID- 17215052
TI  - Acetylcholine injection into the amygdala elicits vocalization in domestic pigs
      (Sus scrofa).
AB  - In a pilot study we have injected the amygdala of five female pigs (age 8 weeks)
      with acetylcholine (ACh, 5.5muM/20mul) and recorded short latency utterances. The
      evoked vocalizations displayed the characteristics of natural screams in sonagram
      appearance and hearing impression. Quantitative analyses, too, revealed the
      similarity of the ACh-evoked vocalizations with natural screaming. The results
      demonstrate for the first time that aversive vocalizations can be triggered by
      cholinergic amygdala stimulation.

PMID- 17215053
TI  - Staphylococcus lugdunensis endocarditis following lower extremity
      revascularization.
AB  - We describe a fatal case of Staphylococcus lugdunensis aortic valve endocarditis
      that was diagnosed in a 75-year-old man approximately 6 months following a lower
      extremity by-pass surgery. A relatively indolent clinical course in the early
      phase following the suspicious exposure may have contributed to a delay in the
      diagnosis. At the time of presentation the patient had evidence of rapidly
      progressive congestive heart failure with anasarca, dyspnea and low grade fevers.
      Blood cultures were positive for coagulase-negative staphylococci and a
      transthoracic echocardiogram was not clearly suggestive of infective
      endocarditis. Despite intense medical treatment the patient expired on day four
      of hospitalization. On post-mortem examination, multiple vegetations were
      observed on the aortic valve and culture identification showed S. lugdunensis.
      Early detection of coagulase-negative bacteremia from multiple blood culture
      samples in this clinical setting is critical and should give rise to a suspicion
      of this rare but often fatal form of infective endocarditis. Besides appropriate
      antibiotic treatment, early surgical referral for valve replacement should be
      considered since it appears to be the only treatment positively affecting
      survival. Finally, further studies are needed to establish the efficacy of
      antibiotic prophylaxis in patients undergoing angiograms with a femoral approach.

PMID- 17215054
TI  - Loser cows in Danish dairy herds: risk factors.
AB  - The objective of our study was to evaluate risk factors for the loser cow state
      in Danish dairy herds. A loser cow was defined on the basis of a clinical
      examination of the individual cow. Recordings of clinical signs were converted
      into a loser cow score and all cows with a loser cow score of 8 or more were
      defined as loser cows. We used correspondence analysis to give a first indication
      of the associations between the proportion of loser cows in the herd and
      potential risk factors. Risk factors were evaluated both at the herd level (39
      herds) and at the cow level (6451 cows) using logistic regression. Conventional
      herds with a high average somatic cell count, hard cubicles and no grazing seem
      to be associated with a high proportion of loser cows. Odds ratio for the loser
      cow state was 4.18 in conventional herds compared to organic herds. Odds ratio
      for the loser cow state was 1.87 for an increase in average weighted mean bulk
      tank somatic cell count of 100,000 cells per ml. We found a statistically
      significant interaction between stall surface and the use of grazing. Odds ratio
      for the loser cow state in herds with soft cubicles and the use of grazing was
      0.09 compared to herds with hard cubicles and no grazing. At the cow level, odds
      ratio for the loser cow state increases significantly with increasing parity.
      Odds ratios for the loser cow state were 1, 2.59 and 6.74 for parity 1, 2, and 3
      or older, respectively. Odds ratio for the loser cow state was significantly
      higher (3.38) for cows giving birth to twins at the last calving before the
      scoring. Additionally, cows scored on pasture had a significantly lower odds
      ratio (0.26) for the loser cow state compared to cows scored in the barn.

PMID- 17215055
TI  - Prevalence of antimicrobial resistance among Salmonella on midwest and northeast
      USA dairy farms.
AB  - The objective of this study was to determine the prevalence of antimicrobial
      resistance among Salmonella isolated from dairy herds in New York, Minnesota,
      Michigan, and Wisconsin, USA. Serogroup and antimicrobial susceptibility
      characteristics were determined for Salmonella from cattle and environmental
      samples collected during August 2000-October 2001 as part of a longitudinal study
      where 129 herds were visited at 2-month intervals. Salmonella isolates were
      tested (using a broth microdilution method) for susceptibility to
      amoxicillin/clavulanic acid, ampicillin, ceftiofur, ceftriaxone, cephalothin,
      chloramphenicol, ciprofloxacin, gentamicin, kanamycin, nalidixic acid,
      streptomycin, sulfamethoxazole, tetracycline, and trimethoprim/sulfamethoxazole.
      Of the 1506 isolates tested for minimum inhibitory concentrations to these 14
      antimicrobial agents, 81.2% were pan-susceptible and for most herds (81.6%) the
      predominant antimicrobial resistance pattern was pan-susceptible. At least 1
      Salmonella isolate resistant to 5 or more antimicrobial agents was found on 23.6%
      of herds. This resistance phenotype was most common among serogroups B and E1 and
      among samples from calves and farmer-designated sick cows. Resistant samples most
      frequently exhibited resistance to tetracycline, streptomycin, and/or ampicillin.
      No samples were resistant to ceftriaxone (though 13 were in the intermediate
      range), and very few samples were resistant to ciprofloxacin (n=1), nalidixic
      acid (n=5), or trimethoprim/sulfamethoxazole (n=7).

PMID- 17215056
TI  - Recombinant sucrose phosphorylase from Leuconostoc mesenteroides:
      characterization, kinetic studies of transglucosylation, and application of
      immobilised enzyme for production of alpha-D-glucose 1-phosphate.
AB  - Sucrose phosphorylase catalyzes the reversible conversion of sucrose (alpha-D
      glucopyranosyl-1,2-beta-D-fructofuranoside) and phosphate into D-fructose and
      alpha-D-glucose 1-phosphate. We report on the molecular cloning and expression of
      the structural gene encoding sucrose phosphorylase from Leuconostoc mesenteroides
      (LmSPase) in Escherichia coli DH10B. The recombinant enzyme, containing an 11
      amino acid-long N-terminal metal affinity fusion peptide, was overproduced 60
      fold in comparison with the natural enzyme. It was purified to apparent
      homogeneity using copper-loaded Chelating Sepharose and obtained in 20% yield
      with a specific activity of 190 Umg(-1). LmSPase was covalently attached onto
      Eupergit C with a binding efficiency of 50% and used for the continuous
      production of alpha-D-glucose 1-phosphate from sucrose and phosphate (600 mM
      each) in a packed-bed immobilised enzyme reactor (30 degrees C, pH 7.0). The
      reactor was operated at a stable conversion of 91% (550 mM product) and
      productivity of approximately 11 gl(-1)h(-1) for up to 600 h. A kinetic study of
      transglucosylation by soluble LmSPase was performed using alpha-d-glucose 1
      phosphate as the donor substrate and various alcohols as acceptors. D- and L
      arabitol were found to be good glucosyl acceptors.

PMID- 17215057
TI  - Effect of radiotherapy and hyperthermia on the tumor accumulation of HPMA
      copolymer-based drug delivery systems.
AB  - Copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) are prototypic and well
      characterized polymeric drug carriers that have been broadly implemented in the
      delivery of anticancer therapeutics. In an attempt to improve the tumor
      accumulation of HPMA copolymer-based drug delivery systems, their in vivo
      application was combined with radiotherapy and hyperthermia. As the effects of
      radiotherapy and hyperthermia were considered to depend significantly on the
      tumor model used, we first analyzed the accumulation of two differently sized
      HPMA copolymers in three different types of tumors, based on the syngeneic
      Dunning rat prostate carcinoma model. Subsequently, in these three models, the
      effects of different doses of radiotherapy and hyperthermia on the tumor
      accumulation of 31 kDa poly(HPMA), 65 kDa poly(HPMA) and 28 kDa poly(HPMA)-GFLG
      doxorubicin were evaluated. It was found that the polymeric drug delivery systems
      accumulated effectively in all three tumor models. In addition, as opposed to
      hyperthermia, radiotherapy was found to improve the concentrations of the
      copolymers independent of the tumor model used. Based on these findings, we
      conclude that radiotherapy is an effective means for increasing the tumor
      accumulation of (polymeric) drug delivery systems, and we propose that the
      combination of carrier-based chemotherapy with radiotherapy holds significant
      potential for improving the treatment of advanced solid malignancies.

PMID- 17215058
TI  - Heavy-metal-induced ethylene production in Arabidopsis thaliana.
AB  - Different plant parts varied in copper sulfate (CuSO(4)) and cadmium sulfate
      (CdSO(4))-induced ethylene production, inflorescences showed the greatest
      induction, while all other plant parts tested produced significantly less. Leaf
      age had a dramatic effect on CuSO(4) and CdSO(4)-induced ethylene production with
      the youngest leaves showing the greatest stimulation and as the age of the leaf
      increased there was a reduction in their ability to produce ethylene. However,
      there was no significant difference in CuSO(4), CdSO(4) and wound-induced
      ethylene production when whole rosettes were taken from plants that were 7, 14 or
      21-day-old. The highest amount of CuSO(4) and CdSO(4)-induced ethylene production
      was produced in the root tip with regions below this producing less. CuSO(4) and
      CdSO(4)-induced ethylene production was also greatest from the tip of the
      inflorescence to 2cm below the tip and from this point down there was a reduction
      in ethylene production. When inflorescence stalks or leaves were treated with
      CuSO(4) or CdSO(4) over a range of concentrations from 0 to 800microM, there was
      an increase in ethylene production starting at 50microM with increasingly greater
      responses up to 400microM. There was no further increase at the 800microM CuSO(4)
      concentration; however, there was a slight decline with 800microM CdSO(4).
      Inflorescence stalks or leaves treated with either 400microM CuSO(4) or CdSO(4)
      exhibited a dramatic increase in ethylene production 2h following treatment
      initiation and remained high over a 24-h period with a decline in ethylene
      production after this time in inflorescence stalks but not the leaves. It was
      found that light caused a dramatic decrease in CuSO(4), CdSO(4) and wound-induced
      ethylene production in both inflorescence stalks and leaves. When inflorescence
      stalks or leaves were treated at 43 degrees C, there was a dramatic effect on
      CuSO(4), CdSO(4) and wound-induced ethylene production in each.

PMID- 17215059
TI  - The participation of hydrogen peroxide in methyl jasmonate-induced NH(4)(+)
      accumulation in rice leaves.
AB  - Ammonium is a central intermediate in the nitrogen metabolism of plants. We have
      previously shown that methyl jasmonate (MJ) not only increases the content of
      H(2)O(2), but also causes NH(4)(+) accumulation in rice leaves. More recently,
      H(2)O(2) is thought to constitute a general signal molecule participating in the
      recognition of and the response to stress factors. In this study, we examined the
      role of H(2)O(2) as a link between MJ and subsequent NH(4)(+) accumulation in
      detached rice leaves. MJ treatment resulted in an accumulation of NH(4)(+) in
      detached rice leaves, which was preceded by a decrease in the activity of
      glutamine synthetase (GS) and an increase in the specific activities of protease
      and phenylalanine ammonia-lyase (PAL). GS, PAL, and protease appear to be the
      enzymes responsible for the accumulation of NH(4)(+) in MJ-treated detached rice
      leaves. Dimethylthiourea (DMTU), a chemical trap for H(2)O(2), was observed to be
      effective in inhibiting MJ-induced NH(4)(+) accumulation in detached rice leaves.
      Scavengers of free radicals (sodium benzoate, SB, and glutathione, GSH), nitric
      oxide donor (N-tert-butyl-alpha-phenylnitrone, PBN), the inhibitors of NADPH
      oxidase (diphenyleneiodonium chloride, DPI, and imidazole, IMD), and inhibitors
      of phosphatidylinositol 3-kinase (wortmannin, WM, and LY 294002, LY), which have
      previously been shown to prevent MJ-induced H(2)O(2) production in detached rice
      leaves, inhibited MJ-induced NH(4)(+) accumulation. Similarly, changes in enzymes
      responsible for NH(4)(+) accumulation induced by MJ were observed to be inhibited
      by DMTU, SB, GSH, PBN DPI, IMD, WM, or LY. Seedlings of rice cultivar Taichung
      Native 1 (TN1) are jasmonic acid (JA)-sensitive and those of cultivar Tainung 67
      (TNG67) are JA-insensitive. On treatment with JA, H(2)O(2) accumulated in the
      leaves of TN1 seedlings but not in the leaves of TNG67. Ethylene action
      inhibitor, silver thiosulfate, was observed to inhibit MJ- and abscisic acid
      induced accumulation of NH(4)(+) and changes in enzymes responsible for NH(4)(+)
      accumulation in detached rice leaves, suggesting that the action of MJ and ABA is
      ethylene dependent.

PMID- 17215060
TI  - A novel adipokinetic peptide in a water boatman (Heteroptera, Corixidae) and its
      bioanalogue in a saucer bug (Heteroptera, Naucoridae).
AB  - The corpora cardiaca (CC) of two water bug species, the water boatman Corixa
      punctata and the saucer bug Ilyocoris cimicoides, contain a substance that cause
      hyperlipemia in the migratory locust. The primary sequence of one octapeptide
      belonging to the adipokinetic hormone (AKH)/red pigment-concentrating hormone
      (RPCH) family was deduced from the multiple MS(N) electrospray mass data of CC
      material from each species. Whereas the saucer bug contains the known octapeptide
      pGlu-Val-Asn-Phe-Ser-Pro-Ser-Trp amide, code-named Anaim-AKH, the water boatman
      has a novel peptide identified as pGlu-Leu/Ile-Asn-Phe-Ser-Pro-Ser-Trp amide,
      code-named Corpu-AKH. The ambiguity about the amino acid at position 2, i.e. Leu
      or Ile, in Corpu-AKH was solved by isolating the peptide in a single-step by
      reversed-phase HPLC and establishing co-elution with the synthetic peptide
      containing Leu at position 2. Functionally, the peptides regulate lipid
      mobilization, as evidenced by an adipokinetic effect after injecting synthetic
      Anaim-AKH and Corpu-AKH into the respective acceptor species. Swimming activity
      of I. cimicoides also causes hyperlipemia.

PMID- 17215063
TI  - Surgical approaches to cavernous haemangiomas of the orbit.
AB  - Cavernous haemangiomas are the most common orbital masses and the second most
      common cause of unilateral proptosis after thyroid ophthalmopathy. We
      retrospectively analysed 19 patients with retrobulbar cavernous haemangiomas, 9
      of whom had lateral orbitotomy to remove retrobulbar cavernous haemangiomas
      located superior (n=4), inferior (n=2) or lateral (n=3) to the optic nerve. Seven
      patients had lateral orbitotomy together with an anterior medial approach to gain
      access to retrobulbar cavernous haemangiomas located medially to the optic nerve
      in the posterior half of the orbit. An anterior approach was used in 3 patient
      with an anteriorly located cavernous haemangioma. We describe here the planning
      of surgical treatment based on the site of the lesion.

PMID- 17215062
TI  - Deficits in working memory and motor performance in the APP/PS1ki mouse model for
      Alzheimer's disease.
AB  - The APP/PS1ki mouse model for Alzheimer's disease (AD) exhibits robust brain and
      spinal cord axonal degeneration and hippocampal CA1 neuron loss starting at 6
      months of age. It expresses human mutant APP751 with the Swedish and London
      mutations together with two FAD-linked knocked-in mutations (PS1 M233T and PS1
      L235P) in the murine PS1 gene. The present report covers a phenotypical analysis
      of this model using either behavioral tests for working memory and motor
      performance, as well as an analysis of weight development and body shape. At the
      age of 6 months, a dramatic, age-dependent change in all of these properties and
      characteristics was observed, accompanied by a significantly reduced ability to
      perform working memory and motor tasks. The APP/PS1ki mice were smaller and
      showed development of a thoracolumbar kyphosis, together with an incremental loss
      of body weight. While 2-month-old APP/PS1ki mice were inconspicuous in all of
      these tasks and properties, there is a massive age-related impairment in all
      tested behavioral paradigms. We have previously reported robust axonal
      degeneration in brain and spinal cord, as well as abundant hippocampal CA1 neuron
      loss starting at 6 months of age in the APP/PS1ki mouse model, which coincides
      with the onset of motor and memory deficits described in the present report.

PMID- 17215064
TI  - Effect of repeated treatment with topiramate on the beta-endorphin plasma level
      in rats selectively bred for high and low alcohol preference.
AB  - Recent research indicates that topiramate has a role in the treatment of alcohol
      dependence. Topiramate has multiple mechanisms of action including enhancement of
      GABA-ergic inhibitory transmission and blocking excitatory glutamate
      neurotransmission, and modulating voltage-gated sodium and calcium ion channels
      and inhibiting carbonic anhydrase. In this study, we examined the effect of
      topiramate on endogenous opioid systems, which have an important role in the
      development of alcohol dependence. We investigated the beta-endorphin plasma
      level of animals with high- and low-risks of alcohol dependency after repeated
      treatment with topiramate. We used the Warsaw High Preferring (WHP) and Warsaw
      Low Preferring (WLP) rats, and treated them with topiramate at a dose of 80 mg/kg
      p.o. for 14 days. In WHP rats treatment with topiramate led to an increase in
      beta-endorphin plasma levels, which persisted at the same level even after a
      single injection of alcohol. The level of this peptide with topiramate was lower
      than in alcohol-injected WHP rats who did not receive topiramate. Beta-endorphin
      levels in WHP rats after topiramate or topiramate and ethanol treatment were
      similar to the basal level of this peptide in WLP rats. In WLP rats, topiramate
      did not prevent the ethanol-induced increase in beta-endorphin plasma level. We
      propose that administration of topiramate may have different effects on the
      opioid system involved in dependence according to genetic susceptibilities to
      alcoholism.

PMID- 17215065
TI  - The delayed genotoxic effect of N-nitroso N-propoxur insecticide in mammalian
      cells.
AB  - The N-nitroso derivative of an extensively used insecticide, propoxur,
      consistently induced dose-responsive chromosome aberrations and sister-chromatid
      exchanges (SCEs) in Chinese hamster ovary (CHO-W8) cells. Further investigations
      indicated that post-treatment incubation with a regular 1.5-cell-cycle period did
      not offer an unbiased estimation of the genotoxicity of N-nitroso carbamate
      insecticides. The scale of chromosome aberration induction increased with
      extension of the post-treatment incubation period. Comparable phenomena were not
      found in CHO-AGT cells proficient for O(6)-methylguanine-DNA-methyltransferase.
      In CHO-W8 cells, pulsed-treatment of the insecticide in the 1st replication cycle
      showed higher SCE induction than in the 2nd cycle. Similar phenomenon was also
      found in SCE induced by N-nitroso derivatives from other carbamate insecticides
      including aldicarb, carbofuran and methomyl. Treated cells did not show
      significantly perturbed cell cycle progression until 12 h after treatment
      removal. Based on the above observations, the O(6)-methylguanine-DNA adduct is
      suggested to be the major lesion caused by the delayed genotoxic effect of N
      methyl carbamate insecticides as described in this report.

PMID- 17215061
TI  - To subjugate NPY is to improve the quality of life and live longer.
AB  - The interactive network of neuropeptide Y (NPY) and cohorts is necessary for
      integrating the hypothalamic regulation of appetite and energy expenditure with
      the endocrine and neuroendocrine systems on a daily basis. Genetic and
      environmental factors that produce an insufficiency of leptin restraint on NPY
      and cognate receptors deregulate the homeostasis to engender various life
      threatening risk factors. Recent studies from our laboratory show that
      neurotherapy consisting of a single central administration of recombinant adeno
      associated virus vector encoding the leptin gene can repress the hypothalamic NPY
      system for the lifetime of rodents. A major benefit of this stable tonic
      restraint is deceleration of pathophysiologic sequalae that shorten life span.
      These include suppression of weight gain, fat accumulation, circulating
      adipokines, amelioration of major symptoms of metabolic syndrome, improved
      reproduction and bone health. Thus, sustained repression of NPY signaling in the
      hypothalamus by leptin transgene expression can improve the quality of life and
      extend longevity.

PMID- 17215066
TI  - Framework for use of toxicity screening tools in context-based decision-making.
AB  - One of the principal applications of toxicology data is to inform risk
      assessments and support risk management decisions that are protective of human
      health. Ideally, a risk assessor would have available all of the relevant
      information on (a) the toxicity profile of the agent of interest; (b) its
      interactions with living systems; and (c) the known or projected exposure
      scenarios: to whom, how much, by which route(s), and how often. In practice,
      however, complete information is seldom available. Nonetheless, decisions still
      must be made. Screening-level assays and tools can provide support for many
      aspects of the risk assessment process, as long as the limitations of the tools
      are understood and to the extent that the added uncertainty the tools introduce
      into the process can be characterized and managed. Use of these tools for
      decision-making may be an end in itself for risk assessment and decision-making
      or a preliminary step to more extensive data collection and evaluation before
      assessments are undertaken or completed and risk management decisions made. This
      paper describes a framework for the application of screening tools for human
      health decision-making, although with some modest modification, it could be made
      applicable to environmental settings as well. The framework consists of problem
      formulation, development of a screening strategy based on an assessment of
      critical data needs, and a data analysis phase that employs weight-of-evidence
      criteria and uncertainty analyses, and leads to context-based decisions. Criteria
      for determining the appropriate screening tool(s) have been identified. The
      choice and use of the tool(s) will depend on the question and the level of
      uncertainty that may be appropriate for the context in which the decision is
      being made. The framework is iterative, in that users may refine the question(s)
      as they proceed. Several case studies illustrate how the framework may be used
      effectively to address specific questions for any endpoint of toxicity.

PMID- 17215067
TI  - Evaluation of protective efficacy of Spirulina fusiformis against mercury induced
      nephrotoxicity in Swiss albino mice.
AB  - The toxicity of mercury to animals and man is well established and this depends
      greatly on the form of the mercury compounds. In most animals' species, including
      man, the kidney is the main site of deposition of inorganic mercury and target
      organ for its toxicity. In the present study Spirulina fusiformis (a
      cyanobacterium, belongs to family--Oscillatoriaceae) has been investigated as a
      possible modifier of mercury induced renal damages in Swiss albino mice. Animals
      were divided into four groups. (i) Control group--only vehicle (0.9% NaCl) was
      administered as i.p. (ii) HgCl(2) treated group--5.0 mg/kg b.wt. HgCl(2) was
      administered as i.p. (iii) Spirulina treated group--800 mg/kg b.wt. Spirulina
      extract was administered orally. (iv) Combination group--S. fusiformis was
      administered 10 days before mercuric chloride administration and continued upto
      30 days after mercuric chloride administration (5.0 mg/kg b.wt.). The animals
      were autopsied on 1, 3, 7, 15 and 30 days after treatment and the activity of
      alkaline phosphatase (ALP), acid phosphatase (ACP), lactate dehydrogenase (LDH)
      and MDA (malondialdehyde) level were measured in kidney homogenates. The results
      indicated that there was a time-dependent significant enhancement in MDA content
      and ACP activity and decrease in LDH and ALP activity observed after HgCl(2)
      treatment. Mercury intoxication also induces pathological alterations in the
      kidney such as degeneration of glomerulus, proximal and distal tubules. A dose
      dependent mortality was also observed following administration of different doses
      of HgCl(2). In combined treatment of Spirulina with HgCl(2), a significant
      decrease in MDA content and ACP activity and elevation in LDH and ALP activity
      was observed as compared to HgCl(2) treated group. Spirulina pre- and post
      treatment with mercury also significantly reduces pathological alterations in
      kidney. Thus, the results from the present study suggest that S. fusiformis can
      significantly modify the renal damages against mercuric chloride induced
      toxicity.

PMID- 17215068
TI  - Mouse model of paraquat-poisoned lungs and its gene expression profile.
AB  - Paraquat (PQ)-induced pulmonary toxicity is characterized by initial development
      of pulmonary edema, infiltration of inflammatory cells, and damage to the
      alveolar epithelium, which may progress to severe fibrosis. However, the exact
      role of PQ in the progression of the pathogenesis has not been clearly
      established. To understand the mechanism of PQ in pulmonary toxicity, we
      developed an animal model of PQ-induced lung injury by intranasal instillation of
      PQ solution using C57Black/6J mice. Twenty microliters of PQ solution (0.01,
      0.01, and 0.04 mg/mouse) was applied through the nares, and the same amount of
      vehicle was applied in control mice. The pathological progression of lung
      pathology in our mouse model was very similar to that of patients suffering from
      PQ poisoning. The lungs of some animals exposed to PQ showed acute fulmination,
      resulting in death from 5 days post-exposure, but others showed a more protracted
      injury, resulting in typical pulmonary fibrosis at 3 weeks. Using this PQ
      poisoned mouse model, we examined the gene expression at the initial destructive
      phase (within 5 days) that fibrosis has not completely developed. We prepared
      RNAs after 6h, 24h, and 5 days and examined the changes of the expression levels
      for 45 selected genes. The genes showing >2-fold increase at 6h or a time
      dependent decrease during this experimental period may be the early markers for
      the destructive phase. These genes are Mt1, Mt2, Hmox1, Gcl, GR, IL-6, IL-13,
      Txn1, Fas, FasL, Lpin2, Mmp1a, Mmp12, Sfp-B, Sfp-D, CAT, EC-SOD, GST, and Pltp.
      On the other hand, the genes involved in the development of fibrosis, such as
      procollagen, Fn1, Eln, SMA, and Mmp9, Timp1 were significantly increased on day
      5, not at 6h nor at 24h, after PQ treatment (the late marker). The genes showing
      a significant increase (Mmp3 and Mmp8) or decrease (VEGFA) at 24h and 5 days and
      not at 6h may be also the late markers. These changes in gene expression, which
      are equalled to functional activities of proteins, will be the targets for future
      studies focused on the development on PQ-induced pulmonary damage.

PMID- 17215069
TI  - Oxidative stress in pneumococcal meningitis: a future target for adjunctive
      therapy?
AB  - Despite antibiotic therapy and supportive intensive care, the morbidity and
      mortality of pneumococcal meningitis remain unacceptably high. During the last
      years, reactive oxygen (ROS) and nitrogen species (RNS), and peroxynitrite, were
      found to be produced in large amounts during pneumococcal meningitis. Although
      most likely intended to fight the invasive pathogens, they seem to lead to
      substantial collateral damage instead. This is because ROS and RNS can exert a
      vast variety of toxic actions, e.g., through lipid peroxidation, DNA strand
      breakage followed by PARP activation and subsequent cellular energy depletion,
      production of inflammatory cytokines, and activation of matrix
      metalloproteinases. Animal models of pneumococcal meningitis have shown that
      these interactions contribute to massive meningeal inflammation, disruption of
      the blood-brain barrier, alterations of the cerebral autoregulation, neuronal
      cell death, and cochlear destruction. Thus, the production of ROS and RNS seems
      at least in part to be responsible for the poor outcome of patients with
      pneumococcal meningitis. In consequence, reactive oxygen and nitrogen species
      such as peroxynitrite have been investigated as potential targets for adjunctive
      therapy in pneumococcal meningitis. Among the multiple agents tested, one
      promising drug is N-acetyl-l-cysteine (NAC), which significantly reduced cerebral
      and cochlear complications in animal models of experimental pneumococcal
      meningitis.

PMID- 17215070
TI  - The HIV-1 central DNA flap region contains a "flapping" third strand.
AB  - Due to the discontinuous nature of HIV-1 plus-strand DNA synthesis, a 99-nt plus
      strand overhang termed the "central DNA flap" is present near the center of the
      proviral DNA prior to integration. The flap appears to have stabilizing and/or
      protective effects on viral DNA, which has been hypothesized to be due to a
      specific conformation adopted by the three-stranded region. The 5' end of the
      flap sequence is very purine rich and has the potential to adopt different
      secondary structures (e.g., duplex, triplex or quadruplex). In the present work,
      circular dichroism spectroscopy and thermal unfolding techniques were used to
      characterize an 89-nt long DNA sequence designed to mimic the three-stranded
      region at the 5' end of HIV-1 proviral DNA. The effect of addition of the HIV-1
      nucleocapsid protein (NC) on the nucleic acid structure was also examined.
      Although, guanine-rich short oligonucleotides derived from the DNA flap
      demonstrated CD spectra characteristic to parallel quadruplexes, this analysis
      reveals that the extended 89-nt construct folds into a canonical duplex with a
      "flapping" third strand both in the absence and presence of NC.

PMID- 17215071
TI  - Activation of phosphatidylinositol 3-kinase/Akt limits FGF-2-induced VEGF release
      in osteoblasts.
AB  - We previously reported that basic fibroblast growth factor (FGF-2) activates
      stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p44/p42
      mitogen-activated protein (MAP) kinase, resulting in the release of vascular
      endothelial growth factor (VEGF) in osteoblast-like MC3T3-E1 cells. In the
      present study, we investigated the role of Akt/protein kinase B in the FGF-2
      stimulated VEGF release in these cells. FGF-2 time-dependently induced the
      phosphorylation of Akt and GSK-3beta, a downstream element of Akt. The Akt
      inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O
      octadecylcarbonate, significantly amplified the FGF-2-induced VEGF release, in a
      dose-dependent manner between 1 and 70microM, while it suppressed the FGF-2
      induced phosphorylation of GSK-3beta. The phosphorylation of Akt induced by FGF-2
      was markedly attenuated by wortmannin and LY294002, inhibitors of
      phosphatidylinositol 3-kinase (PI3-kinase) in osteoblast-like MC3T3-E1 cells.
      Both wortmannin and LY294002 enhanced the FGF-2-induced VEGF release. In
      addition, Akt inhibitor had no significant effect on the FGF-2-induced
      phosphorylation of p44/p42 MAP kinase and SAPK/JNK. Furthermore, the FGF-2
      induced Akt phosphorylation was not affected by PD98059, a MEK inhibitor, or
      SP600125, a SAPK/JNK inhibitor. Taken together, our findings strongly suggest
      that PI3-kinase/Akt plays an inhibitory role in FGF-2-induced VEGF release in
      osteoblasts.

PMID- 17215072
TI  - Angiotensin II activates p44/42 MAP kinase partly through PKCepsilon in H295R
      cells.
AB  - Using pharmaceutical and overexpression approaches we have previously reported
      that in H295R cells, (a) angiotensin II (AII) activates PKCepsilon, PKCalpha and
      p44/42 MAPK pathway, (b) PKCepsilon, PKCalpha and p44/42 MAPK overexpression
      inhibits AII-induced CYP11B2 gene transcription and (c) overexpression of
      PKCepsilon inhibits CYP11B2 gene transcription through p44/42 MAPK activation
      [LeHoux, J.G., Dupuis, G., Lefebvre, A., 2001. Control of CYP11B2 gene expression
      through differential regulation of its promoter by atypical and conventional
      protein kinase C isoforms. J. Biol. Chem. 276 (11), 8021-8028; LeHoux, J.G.,
      Lefebvre, A., 2006. Novel protein kinase C-epsilon inhibits human CYP11B2 gene
      expression through ERK1/2 signalling pathway and JunB. J. Mol. Endocrinol. 36
      (1), 51-64]. The aim of the present work was to evaluate the physiological role
      of endogenous PKCepsilon and PKCalpha isoforms in the activation of p44/42 MAPK
      by AII. A 50% reduction of PKCepsilon protein by siRNA-PKCepsilon resulted in 35%
      inhibition of AII-induced p44/42 MAPK activation. Knockdown of PKCepsilon
      stimulated AII-induced CYP11B2 transcription indicating that the PKCepsilon is
      not involved in the activation of CYP11B2 gene expression by AII. Furthermore,
      knockdown of PKCalpha enhanced AII-stimulated CYP11B2 transcription without
      altering p44/42 MAPK indicating that inhibition of AII-stimulated CYP11B2 gene by
      PKCalpha does not involve the p44/42 MAPK signalling pathway. These results thus
      establish that physiologically, PKCepsilon and PKCalpha act through different
      signalling pathways to inhibit AII-stimulated CYP11B2 gene expression.

PMID- 17215073
TI  - Role of MAPKs in angiotensin II-induced steroidogenesis in rat glomerulosa cells.
AB  - Angiotensin II is one of the most important stimuli of rat adrenal glomerulosa
      cells, stimulating both steroid secretion and growth. In a previous report, we
      had shown that Ang II promotes cellular hypertrophy, but not proliferation, in
      rat adrenal glomerulosa cells maintained in primary culture for 3 days. The
      inhibition of proliferation and stimulation of hypertrophy induced by Ang II
      involves both p42/p44(mapk) and p38 MAPK activation. The increase in cell protein
      content induced by Ang II entails formation of a cortical actin ring and Rac
      dependent activation of p42/p44(mapk) and p38 MAPK. The present study summarizes
      these results and provides evidences that Ang II-induced activation of
      p42/p44(mapk) and p38 MAPK are implicated in aldosterone secretion by enhancing
      expression of specific steroidogenic proteins such as StAR and 3beta-HSD.

PMID- 17215074
TI  - Reduction of tumorigenesis and invasion of human breast cancer cells by whey
      acidic protein (WAP).
AB  - Whey acidic protein (WAP) is a major component of whey, which has two or three
      WAP motif domains characterized by a four-disulfide core (4-DSC) structure
      similar to the serine protease inhibitor. We have previously found that WAP
      inhibits the proliferation of mammary epithelial cells in vitro and in vivo [N.
      Nukumi, K. Ikeda, M. Osawa, T. Iwamori, K. Naito, H. Tojo, Regulatory function of
      whey acidic protein in the proliferation of mouse mammary epithelial cells in
      vivo and in vitro, Dev. Biol. 274 (2004) 31-44]. We report herein that WAP also
      reduces the progression of human breast cancer cells (MCF-7 and MDA-MB-453
      cells). We have demonstrated that the forced expression of WAP in MCF-7 cells
      reduces the proliferation in either the presence or absence of estrogen. The
      tumor progression of WAP-expressing MCF-7 cells in nude mice is significantly
      suppressed more than that of mock-MCF-7 cells following the reduced expression of
      angiopoietin-2 gene. We have confirmed that the invasive activity of breast
      cancer cells is reduced to approximately 30% of that of mock cells by the forced
      expression of exogenous WAP through its inhibition of degradation of laminin.
      These data suggest that WAP has a protease-inhibitory function on the progression
      of breast cancer cells. It is therefore possible to utilize WAP as therapeutic
      protein against tumorigenesis of breast cancer.

PMID- 17215075
TI  - Inhibition of estrogen-induced mammary tumor formation in MMTV-aromatase
      transgenic mice by 4-chlorophenylacetate.
AB  - Treatment of estrogen-sensitive breast cancer with selective estrogen selective
      modulators (SERMs) and, more recently, aromatase inhibitors has met with wide
      success. However, antagonism of estrogen receptor (ER) activity in breast
      carcinomas by SERMs such as tamoxifen has been associated with increased risk of
      cancer in other tissue such as the endometrium. Furthermore, current therapies
      using aromatase inhibitors have side effects on bone resulting in development of
      osteoporosis in some patients. We present in this paper the results of a study
      using 4-chlorophenylacetate (4-CPA), a compound which belongs to a family of
      small aromatic fatty acids that has been shown to possess anticancer properties,
      to treat DMBA exposed MMTV-aromatase mice. These animals exhibit elevated levels
      of estrogen in their mammary glands and develop estrogen-responsive tumors.
      Consistent with our earlier findings showing that 4-CPA inhibited the growth of
      ER positive breast cancer cells in vitro, we now demonstrate that this compound
      inhibits tumor formation in MMTV-aromatase mice. This effect was not associated
      with reduction of ER expression in their mammary tissue, or to alteration of
      aromatase levels or activity. The data suggest that 4-CPA is a novel therapeutic
      agent that could be used in the prevention or treatment of estrogen-sensitive
      breast cancer.

PMID- 17215076
TI  - Up-regulation of fibroblast growth factor 3 is associated with tumor metastasis
      and recurrence in human hepatocellular carcinoma.
AB  - Recently, we established a hepatocellular carcinoma (HCC) cell line (named H4-M)
      from a metastatic HCC tumor. In H4-M, a marker chromosome containing a
      homogeneously staining region (hsr) was identified by cytogenetic analysis. The
      hsr was characterized by chromosome microdissection and the result showed that
      the hsr was composed of DNA sequence from 11q13. Oncogenes CCND1 and FGF3 were
      localized within the complicon and overexpressions of CCND1 and FGF3 were
      confirmed by Northern blot analysis. Clinical significance of FGF3 overexpression
      was studied by immunohistochemistry (IHC) using an HCC tissue microarray (TMA)
      containing 60 pairs of primary/metastatic HCCs and 30 pairs of primary/recurrent
      HCCs. TMA study showed that overexpression of FGF3 was significantly associated
      with HCC metastasis and recurrence (p<0.01), suggesting that up-regulation of
      FGF3 may play an important role in HCC metastasis and recurrence.

PMID- 17215077
TI  - Relationship of cellular immunity, cytokines and CRP with clinical course in
      breast cancer patients with endocrine-dependent distant metastases treated with
      immunotherapy.
AB  - We have reported important benefits and survival with an immunotherapy schedule
      in patients with endocrine-dependent breast cancer and distant metastases. Here
      clinical outcome is updated and its correlation with new immunological data is
      shown. In 32 evaluated breast cancer patients with endocrine-dependent distant
      metastases treated with a new immunotherapy schedule (cyclic administration of
      beta-interferon and interleukin-2), cellular immunity, cytokines and CRP were
      related to the clinical course. Estimated and true 5-10 year overall survival
      rates from first line antiestrogen and distant metastases were higher than
      previously reported in a similar population. Interleukin-2 administration was
      followed by a significant increase in total lymphocytes, CD4+, CD8+, CD16+56+
      (NK) cells, IL-6, IL-12, and CRP (from P<0.04 to P<0.000) but no change in IL-10
      and TGFbeta1 during clinical benefit. During progressive disease no change was
      observed in the former parameters, concomitant with a significant increase in IL
      10 (P=0.020) and a significant decrease in TGFbeta1 (P=0.023). These findings
      confirm that cellular immunity is significantly stimulated by IL-2 only during
      clinical benefit. Furthermore, these results demonstrate that different changes
      of proinflammatory cytokines, CRP and inhibiting factors are consistent with
      associated clinical benefit or with disease progression, respectively.

PMID- 17215078
TI  - Hypoxia inducible factor 1-alpha expression as a factor predictive of efficacy of
      taxane/platinum chemotherapy in advanced primary epithelial ovarian cancer.
AB  - To investigate the impact on survival of HIF 1-alpha expression on primary
      advanced epithelial ovarian cancer (EOC), we examined the correlations between
      prognosis and HIF 1-alpha expression by Western blot analysis in 52 cases of
      stage III/IV EOC. HIF 1-alpha expression was confirmed in 36 cases (69.2%) of
      EOC, and HIF 1-alpha-expressing tumors had a significantly higher rate of
      response (p<0.01) to postoperative paclitaxel/carboplatin combination
      chemotherapy (TC) than tumors without HIF1-alpha expression. Moreover, patients
      with HIF 1-alpha-expressing tumors with suboptimal resection of stage III/IV
      tumors indicated for postoperative TC exhibited significantly better survival
      (p<0.01).

PMID- 17215079
TI  - Photocatalytic degradation of triazophos in aqueous titanium dioxide suspension:
      identification of intermediates and degradation pathways.
AB  - The photocatalytic degradation of triazophos in aqueous TiO2 suspension has been
      studied in a photoreactor operating with simulated solar radiation. The decrease
      in triazophos concentration followed first-order kinetics with a half-life of
      4.76+/-0.42 h at a TiO2 suspension concentration of 10 mg/L. Seventeen
      degradation products were identified using HPLC-UV, HPLC/MS/MS, GC/MS/MS and IC,
      and by comparing retention times and spectra with commercially available
      authentic standards. On the basis of the observed transformation products, two
      routes were proposed, one based on the initial oxidative cleavage of PS bond to
      PO bond, and the other on initial cleavage of the ester P-O bonds. Photocatalysis
      holds promise for the solar treatment of pesticide-contaminated waters.

PMID- 17215082
TI  - Comment on the comprehensive review of chronic pain by Vierck and the topical
      review of pain by Klossika et al.

PMID- 17215080
TI  - Descending analgesia--when the spine echoes what the brain expects.
AB  - Changes in pain produced by psychological factors (e.g., placebo analgesia) are
      thought to result from the activity of specific cortical regions. However,
      subcortical nuclei, including the periaqueductal gray and the rostroventral
      medulla, also show selective activation when subjects expect pain relief. These
      brainstem regions send inhibitory projections to the spine and produce diffuse
      analgesic responses. Regrettably the precise contribution of spinal mechanisms in
      predicting the strength of placebo analgesia is unknown. Here, we show that
      expectations regarding pain radically change the strength of spinal nociceptive
      responses in humans. We found that contrary to expectations of analgesia,
      expectations of hyperalgesia completely blocked the analgesic effects of
      descending inhibition on spinal nociceptive reflexes. Somatosensory-evoked brain
      potentials and pain ratings further confirmed changes in spino-thalamo-cortical
      responses consistent with expectations and with changes in the spinal response.
      These findings provide direct evidence that the modulation of pain by
      expectations is mediated by endogenous pain modulatory systems affecting
      nociceptive signal processing at the earliest stage of the central nervous
      system. Expectation effects, therefore, depend as much about what takes place in
      the spine as they do about what takes place in the brain. Furthermore, complete
      suppression of the analgesic response normally produced by descending inhibition
      suggests that anti-analgesic expectations can block the efficacy of
      pharmacologically valid treatments which has important implications for clinical
      practice.

PMID- 17215083
TI  - Inelastic electron holography as a variant of the Feynman thought experiment.
AB  - Using a combination of electron holography and energy filtering, interference
      fringes produced after inelastic interaction of electrons with hydrogen molecules
      are examined. Surprisingly, the coherence of inelastic scattering increases when
      moving from the surface of a hydrogen-containing bubble to the vacuum. This
      phenomenon can be understood in terms of the Feynman two-slit thought experiment
      with a variable ambiguity of the which-way registration.

PMID- 17215084
TI  - Protective effects of carotenoids from saffron on neuronal injury in vitro and in
      vivo.
AB  - Crocus sativus L. (saffron) has been used as a spice for flavoring and coloring
      food preparations, and in Chinese traditional medicine as an anodyne or
      tranquilizer. Our previous study demonstrated that crocin, a carotenoid pigment
      of saffron, can suppress the serum deprivation-induced death of PC12 cells by
      increasing glutathione (GSH) synthesis and thus inhibiting neutral
      sphingomyelinase (nSMase) activity and ceramide formation. The carotenoid
      pigments of saffron consist of crocetin di-(beta-d-glucosyl)-ester [dicrocin],
      crocetin-(beta-d-gentiobiosyl)-(beta-d-glucosyl)-ester [tricrocin] and crocetin
      di-(beta-d-gentiobiosyl)-ester [crocin]. Saffron also contains picrocrocin, the
      substance causing saffron's bitter taste. In this study, to confirm whether
      neuroprotective effects of saffron are caused solely by crocin, we examined the
      antioxidant and GSH-synthetic activities of these crocins in PC12 cells under
      serum-free and hypoxic conditions. Measurements of cell viability, peroxidized
      membrane lipids and caspase-3 activity showed that the rank order of the
      neuroprotective potency at a concentration of 10 muM was
      crocin>tricrocin>dicrocin and picrocrocin (the latter two crocins had a little or
      no potency). In addition, we show that among these saffron's constituents, crocin
      most effectively promotes mRNA expression of gamma-glutamylcysteinyl synthase
      (gamma-GCS), which contributes to GSH synthesis as the rate-limiting enzyme, and
      that the carotenoid can significantly reduce infarcted areas caused by occlusion
      of the middle cerebral artery (MCA) in mice.

PMID- 17215085
TI  - Inflammatory markers in patients with severe burn injury. What is the best
      indicator of sepsis?
AB  - OBJECTIVE: To estimate the diagnostic value of serum PCT, CRP, leukocyte count
      and temperature as markers of sepsis in critically ill ICU burn patients. DESIGN
      AND SETTING: Prospective, observational study in a four bed Burn Intensive Care
      Unit. PATIENTS: Forty-three patients admitted in a Burn ICU were included in our
      study. MEASUREMENTS AND RESULTS: Serum PCT, CRP concentrations, WCC (white cell
      count), neutrophils and temperature were measured within the first 24h after-burn
      and daily thereafter. Severity of organ failure was estimated by sequential organ
      failure assessment (SOFA) score. Every day we classified all patients in one of
      the following three categories: non-systemic inflammatory condition (non-SIRS),
      SIRS non-infected and SIRS 2 infected or sepsis. Patients with infected SIRS
      differ significantly from non-infected SIRS in PCT (11.8+/-15.8 versus 0.63+/
      0.0.43, respectively, p < 0.001). On the other hand, WCC, temperature and
      neutrophils did not differ significantly between patients with SIRS non-infected
      and infected SIRS. CRP was elevated in all three groups but didn't differ
      significantly between SIRS non-infected and septic patients. Area under receiver
      operating curves was 0.975 and showed reasonable discriminative power (p = 0.002,
      95% CI, 0.91-1.035) in predicting of sepsis only for PCT. CONCLUSIONS: Serum
      procalcitonin levels can be used as an early indicator of septic complication in
      patients with severe burn injury.

PMID- 17215086
TI  - Skin biopsy findings: implications for the pathophysiology of fibromyalgia.
AB  - The mechanisms responsible for symptom expression in fibromyalgia (FM) are
      complex. The most consistently detected objective abnormalities in FM involve
      pain-processing systems. Up to recently, central nervous system was a primary
      focus of investigations in FM. Although it is unlikely that FM occurs because of
      primary disorders of the peripheral tissues, there are still data to suggest that
      some abnormalities can be detected in the periphery. With the recognition of
      abnormalities in skin of some FM patients, it is now apparent that the role of
      peripheral nerve endings in FM is much greater than previously thought. The aim
      of this paper is to review literature concerning the skin biopsy findings of FM
      patients and discuss their potential relevance to FM. This paper suggests that
      patients with FM represent a state of the dysfunction of descending,
      antinociceptive pathways and low hypothalamic-pituitary-adrenal function. This
      state is further proposed to result in many skin biopsy findings associated with
      the disorder, including increased N-methyl-d-aspartate receptors subtype 2D
      expression, neurogenic inflammation and characteristic electron microscopic
      findings. Future direction of research would be identification of specific
      laboratory markers such as skin biopsy for diagnostic and clinical evaluation
      purposes in FM.

PMID- 17215087
TI  - Statins may be beneficial for patients with slow coronary flow syndrome due to
      its anti-inflammatory property.
AB  - The phenomenon of slow progression of angiographic contrast in the coronary
      arteries in the absence of stenosis in the epicardial vessels in some patients
      presenting with chest pain has been recently called as slow coronary flow
      syndrome because the underlying pathophysiological mechanisms as well as
      therapeutics of this unique phenomenon is less well understood. Although this
      phenomenon was first reported on in 1972 by Tambe, few studies have focused on
      the etiology of this unique angiographic finding since that time. Several
      hypotheses have been poised to elucidate this phenomenon, including a form of
      early phase of atherosclerosis, small vessel dysfunction, Hagen-Poiseuille's
      equation model, imbalance between vasoconstrictor and vasodilatory factors, and
      platelet function disorder. During the last several years there has been arisen
      the most interesting concept of "atherosclerosis as a inflammation disease",
      which is involving the different entities of coronary artery disease covering
      slow coronary flow syndrome. The angiographic finding appeared as slow flow is an
      important clinical entity because it may be the cause of angina at rest or during
      exercise, acute myocardial infarction, and hypertension. Despite the good
      prognosis, patients complained commonly of persistent uncomfortable chest, which
      can significantly impair quality of life. There is no effective therapy for
      patients with slow coronary flow syndrome up to now. Statins have been showed the
      important benefits for the large populations of individuals at high risk of
      coronary artery disease. In addition to lowering lipid profile, statins have
      pleiotropic effects on improving vascular function. Increasing evidence, suggests
      that reduction of cardiovascular events conferred by statins relates not only to
      cholesterol lowering but also to direct effects on endothelium function as well
      as anti-thrombotic and anti-inflammatory actions. Accordingly, we hypotheses that
      these pleiotropic effects of statin may be beneficial for patients with slow
      coronary flow syndrome due to its pharmacological basis.

PMID- 17215088
TI  - Radical scavenging activity and composition of raspberry (Rubus idaeus) leaves
      from different locations in Lithuania.
AB  - Raspberry (Rubus idaeus) leaves, collected in different locations of Lithuania
      were extracted with ethanol and the extracts were tested for their antioxidant
      activity (AA) by using ABTS(.)(+) decolourisation and DPPH(.) scavenging methods.
      All extracts were active, with radical scavenging capacity at the used
      concentrations from 20.5 to 82.5% in DPPH(.) reaction system and from 8.0 to
      42.7% in ABTS(.)(+) reaction. The total amount of phenolic compounds in the
      leaves varied from 4.8 to 12.0 mg of gallic acid equivalents (GAE) in 1 g of
      plant extract. Quercetin glucuronide, quercetin-3-O-glucoside and rutin were
      identified in the extracts.

PMID- 17215089
TI  - Passiflora alata and Passiflora edulis spray-dried aqueous extracts inhibit
      inflammation in mouse model of pleurisy.
AB  - The aqueous leaves extracts of Passiflora alata (100-300 mg/kg, i.p.) and
      Passiflora edulis (100-1000 mg/kg, i.p.) possess a significant antiinflammatory
      activity on carrageenan-induced pleurisy in mice. Treatment with the extracts
      inhibited leukocyte migration and reduced the formation of exudate. Moreover, a
      significant inhibition of myeloperoxidase and adenosine-deaminase activities was
      observed at the doses tested (100 or 250 mg/kg, i.p.). At the same doses, a
      significant decrease of serum C-reactive protein was observed.

PMID- 17215090
TI  - Radical scavenging capacity of Agrimonia eupatoria and Agrimonia procera.
AB  - The antioxidant activity of Agrimonia eupatoria (Agrimony) and Agrimonia procera
      (Fragrant agrimony) extracts was assessed by measuring in DPPH radical scavenging
      and ABTS(+) radical decolourisation reaction systems. Radical scavenging capacity
      of agrimony extracts varied in a wide range (9.1-97.5% in DPPH reaction and 6.7
      79.5% in ABTS reaction) depending on the polarity of the solvent used to obtain
      the extract.

PMID- 17215091
TI  - The psychology of time.

PMID- 17215092
TI  - Protection of pigs against post-weaning multisystemic wasting syndrome by a
      recombinant adenovirus expressing the capsid protein of porcine circovirus type
      2.
AB  - Post-weaning multisystemic wating syndrome (PMWS) associated with PCV2 was one of
      the most costly diseases currently faced by the swine industry. In order to
      develop a vaccine to control this disease, we previously constructed a
      recombinant adenovirus expressing the capsid of PCV2. Here, we examined the
      protection of swine against PMWS by the recombinant adenovirus. Eighteen 32-day
      old pigs were assigned to three groups each with six. Group 1 was vaccinated
      subcutaneously with rAd-Cap and boosted 2 weeks later. Thirty-seven days after
      first vaccination, Groups 1 and 2 were oronasally challenged with virulent PCV2
      isolate, 4 and 7 days later, intramuscularly exposed to keyhole limpet hemocyanin
      (KLH). Group 3 remained unchallenged but with KLH. The results showed that high
      level of PCV2-specific ELISA antibody and neutralizing antibody could be induced
      at 37 days after first vaccination. After challenge, pigs in vaccinated group had
      no clearly clinical signs, although some of them had increased rectal
      temperatures (>/=40 degrees C) for short time. The pyrexic phase in vaccinated
      group was significantly lighter than that in challenge-control group (P<0.05).
      The relative daily weight gain in vaccinated-challenged group was similar to that
      in empty control group. But it was significantly high compared to the challenge
      control group (P<0.05). Mean while the pathological lesions and virema presented
      in vaccinated group were milder than those in control group. It indicated that
      the recombinant adenovirus was able to confer significant protection against
      clinical disease and reduce pathogenic lesions induced by PCV2 challenge, even
      though it could not provide complete virological protection. The recombinant
      adenovirus might be an attractive candidate vaccine for preventing the disease
      associated with PCV2 infection.

PMID- 17215093
TI  - Serological and molecular evidence that canine respiratory coronavirus is
      circulating in Italy.
AB  - Canine respiratory coronavirus (CRCoV) is a group II coronavirus that was firstly
      identified in lung samples of dogs with canine infectious respiratory disease
      (CIRD) in UK in 2003. We report for the first time the identification of CRCoV in
      Italy, together with serological evidence that the virus has been circulating in
      the Italian dog population as from 2005. Serological investigations on 216 dog
      sera, carried out by an ELISA test using the strictly related bovine coronavirus
      (BCoV) as antigen, revealed an overall CRCoV seroprevalence of 32.06% in the last
      2 years. RT-PCR targeting the S-gene of CRCoV was carried out on 109 lung samples
      collected from carcasses of dogs submitted for diagnostic investigations.
      Positive results were obtained from the lungs of a dog of the Apulia region that
      was co-infected with canine parvovirus type 2. Sequence analysis of the S-gene
      fragment amplified by RT-PCR (595bp) showed similarity to group II coronaviruses,
      with the highest nucleotide identity (98%) to the only CRCoV strain currently
      available in the GenBank database (strain T101). The results of the present study
      show that CRCoV is present also in continental Europe, although further studies
      are required to determine the real pathogenic potential of the virus.

PMID- 17215094
TI  - Comment on: "A cascade analysis of the interaction of mercury and
      coproporphyrinogen oxidase (CPOX) polymorphism on the heme biosynthetic pathway
      and porphyrin production" by Heyer et al. [Toxicol. Lett. 161 (2006) 159-166].

PMID- 17215095
TI  - Effects of fusion/activation methods on development of embryos produced by
      nuclear transfer of porcine fetal fibroblast.
AB  - The present studies were carried out to investigate the effects of intensity of
      dc pulse, number of dc pulse and equilibration before fusion/activation on
      developmental ability of porcine embryos derived from nuclear transfer. In
      experiment 1, different fusion/activation intensity (two dc pulses of 0.4, 0.8,
      1.2, 1.6 and 2.0 kV/cm for 30 micros, respectively) was carried out to
      investigate development of embryos. In experiment 2, the reconstructed oocytes
      were fused and activated with one, two or three dc pulses of 1.2 kV/cm for 30
      micros. In experiment 3, reconstructed oocytes were equilibrated in TCM-199
      medium for 0-6 h, respectively, and fused/activated with one dc pulse of 1.2
      kV/cm for 30 micros. The reconstructed embryos were cultured in PZM-3 medium
      containing 0.3% BSA. When oocytes were fused with donor cell by two dc pulses of
      0.4 kV/cm for 30 micros, the rates of cleavage and blastocyst formation were
      significantly lower (32.9% and 2.5%) than those of fused by 0.8 kV/cm (59.0% and
      17.4%) or 1.2 kV/cm (63.3% and 18.4%), respectively. One dc pulse of 1.2 kV/cm
      for 30 micros was enough to fuse and activate embryos to develop to blastocyst
      (24.8%). Equilibration for 2-3 h in TCM-199 before fusion/activation was
      beneficial for improving the developmental ability of embryos produced by nuclear
      transfer (25.6-23.3% at blastocysts).

PMID- 17215096
TI  - Ethnobotanical study of medicinal plants used by the Andean people of Canta,
      Lima, Peru.
AB  - A survey aiming to document medicinal plant uses was performed in Canta Province
      Lima Department, in the Peruvians Andes of Peru. Hundred and fifty people were
      interviewed. Enquiries and informal personal conversations were used to obtain
      information. Informants were men and women over 30 years old, who work in
      subsistence agriculture and cattle farming, as well as herbalist. Eighty-seven
      species were collected and identified that had indigenous uses. Common names,
      habit, part of the plant used, preparation, administration and illnesses treated
      were recorded for each species. Results are compared with other
      ethnopharmacological studies performed in the Peruvian Andes.

PMID- 17215097
TI  - BIRADS ultrasonography.
AB  - The fourth edition of the BIRADS mammography appeared in 2003 and is now
      associated with the first editions of the BIRADS ultrasound and MRI. BIRADS is a
      system of assistance to the drafting of the reports more and more used in the
      world and soon directly implemented on mammography and ultrasound units. The
      categories of evaluation of the BIRADS allow a clear synthesis of the descriptive
      data resulting from the use of the lexicon and invite the radiologist to a
      reasoned, objective and less intuitive step. They give an action to be taken and
      responsibility to the radiologist and the referring physicians in the assumption
      of the patients.

PMID- 17215098
TI  - Carbon film resistor electrode for amperometric determination of acetaminophen in
      pharmaceutical formulations.
AB  - Flow injection analysis (FIA) with amperometric detection was employed for
      acetaminophen quantification in pharmaceutical formulations using a carbon film
      resistor electrode. This sensor exhibited sharp and reproducible current peaks
      for acetaminophen without chemical modification of its surface. A wide linear
      working range (8.0x10(-7) to 5.0x10(-4) mol L(-1)) in phosphate buffer solution
      as well as high sensitivity (0.143 A mol(-1) L cm(-2)) and low submicromolar
      detection limit (1.36x10(-7) mol L(-1)) were achieved. The repeatability (R.S.D.
      for 10 successive injections of 5.0x10(-6) and 5.0x10(-5) mol L(-1) acetaminophen
      solutions) was 3.1 and 1.3%, respectively, without any memory effect between
      injections. The new procedure was applied to the analyses of commercial
      pharmaceutical products and the results were in good agreement with those
      obtained utilizing a spectrophotometric method. Consequently, this amperometric
      method has been shown to be very suitable for quality control analyses and other
      applications with similar requirements.

PMID- 17215099
TI  - Initial and long-term outcome after palliative surgical drainage of 269 patients
      with malignant biliary obstruction.
AB  - AIMS: This study aimed to analyse the current outcome after palliative surgical
      drainage of malignant biliary obstruction. METHOD: From 1992 to 2003,
      perioperative parameters and the incidence and indications of readmissions were
      analysed in 269 patients who underwent a palliative biliary bypass for
      periampullary carcinoma. RESULTS: Hospital mortality occurred in seven patients
      and median postoperative stay was 10 days. Anastomotic leakage occurred in three
      patients and intraabdominal haemorrhage in eight patients. Overall 75 patients
      experienced a complication. Nine patients underwent a relaparotomy during initial
      hospital admission. Overall, 142 patients were readmitted, 13 for indications
      related to the biliary bypass, 11 for surgery-related indications. Twenty-five
      patients were readmitted for radiochemotherapy, 112 for progressive disease and
      23 for indications not related to the disease. Median survival was 7.5 months and
      the 3-year survival 3%. Survival was significantly lower in patients with
      metastases and in those who underwent elective bypass for gastric outlet
      obstruction. CONCLUSION: Current hospital mortality after palliative biliary
      bypass as well as readmission rates for complications related to the biliary
      bypass or surgical procedure are low. Surgical biliary bypass is a safe and
      effective palliative treatment for patients with malignant biliary obstruction.

PMID- 17215100
TI  - The surgical management of patients who achieve a complete pathological response
      after primary chemotherapy for locally advanced breast cancer.
AB  - AIMS: Our aim was to investigate the role of minimal surgery in patients with
      locally advanced breast cancer (LABC) who achieve a complete pathological (pCR)
      response to primary chemotherapy (PC) and evaluate subsequent local recurrence
      (LRR), disease free survival (DFS) and overall survival (OS). METHODS: Between
      January 2000 and April 2005, 101 patients with operable LABC (T2, T3, N0 or N1,
      M0) who were not suitable for conservation surgery were treated with PC. Patients
      were treated with doxorubicin and cyclophosphamide for four cycles (100 patients)
      then four cycles with paclitaxel (91 patients). Post-PC surgery consisted of
      multiple core biopsies and axillary clearance for patients with a complete
      clinical and radiological response. If a pCR was confirmed no further breast
      surgery was performed. The remaining patients were treated with breast conserving
      surgery or mastectomy and axillary clearance as appropriate. Adjuvant
      radiotherapy was given to all patients. RESULTS: Breast conservation was possible
      in 60% of patients. Overall, 20 patients achieved a pCR of which 16 were
      confirmed on core biopsies alone. All patients were followed-up for a mean of
      33.5 months (95% CI, 30.3-36.7). There were 10 local recurrences, four following
      mastectomy, four after wide excision and two after core biopsies. There was no
      difference in DFS (chi square=0.18; p=0.67) or OS (chi square=0.67; p=0.41)
      between patients achieving a pCR and the remainder. CONCLUSIONS: The local
      recurrence rate of these poor prognosis patients is similar to other reported
      series but higher than in our previously reported series of patients managed
      according to the same protocol. Our current management therefore now includes pre
      treatment marking and subsequent surgical excision.

PMID- 17215101
TI  - Epidemiology and treatment of extramammary Paget disease in the Netherlands.
AB  - AIM: To determine the incidence of EMPD and to describe its epidemiology,
      treatment, survival and the risk of developing other malignancies. METHOD: All
      cases of EMPD, diagnosed between 1989 and 2001, were selected from the
      Netherlands Cancer Registry. RESULTS: In total, 178 cases of invasive and 48
      cases of in situ EMPD had been registered. The overall relative 5-year survival
      for invasive tumours was 72%. Most patients with invasive as well as in situ
      cancer underwent surgery. Other malignancies were found in 32% of patients with
      invasive EMPD and 35% of patients with in situ EMPD. Patients had an increased
      risk of developing a second primary cancer (standardized incidence ratio: 1.7;
      95% confidence interval 1.2-2.4). The most frequent localizations of the other
      cancers were the colorectum, the prostate, the breast and the extragenital skin.
      CONCLUSIONS: For EMPD, which is a rare disease in the Netherlands, there are no
      clear diagnostic and treatment guidelines. The prognosis is fairly good. A
      thorough search for other tumours is recommended for these patients.

PMID- 17215102
TI  - Polymorphisms of short tandem repeat of genes and breast cancer susceptibility.
AB  - AIM: To explore the relationship of short tandem repeat polymorphisms and breast
      cancer susceptibility. METHODS: We searched the MEDLINE database (up to June
      2006) with the keywords of tandem repeat sequences, gene polymorphisms, breast
      cancer, cancer susceptibility and microsatellite instability. We reviewed the
      literature on gene polymorphisms, especially the relationship of short tandem
      repeat and breast cancer risk. RESULTS: We focused on the candidate genes sex
      hormones, steroid hormone and receptors, carcinogen metabolism, cell
      proliferation regulation and other genes. CONCLUSIONS: The functional effects of
      short tandem repeat polymorphisms on cancer susceptibility, especially on breast
      cancer risk, are identified. The importance of short tandem repeat polymorphisms
      on development and progression of breast cancer are discussed.

PMID- 17215103
TI  - Automatic segmentation and 3D reconstruction of intravascular ultrasound images
      for a fast preliminar evaluation of vessel pathologies.
AB  - Intravascular ultrasound (IVUS) imaging is used along with X-ray coronary
      angiography to detect vessel pathologies. Manual analysis of IVUS images is slow
      and time-consuming and it is not feasible for clinical purposes. A semi-automated
      method is proposed to generate 3D reconstructions from IVUS video sequences, so
      that a fast diagnose can be easily done, quantifying plaque length and severity
      as well as plaque volume of the vessels under study. The methodology described in
      this work has four steps: a pre-processing of IVUS images, a segmentation of
      media-adventitia contour, a detection of intima and plaque and a 3D
      reconstruction of the vessel. Preprocessing is intended to remove noise from the
      images without blurring the edges. Segmentation of media-adventitia contour is
      achieved using active contours (snakes). In particular, we use the gradient
      vector flow (GVF) as external force for the snakes. The detection of lumen border
      is obtained taking into account gray-level information of the inner part of the
      previously detected contours. A knowledge-based approach is used to determine
      which level of gray corresponds statistically to the different regions of
      interest: intima, plaque and lumen. The catheter region is automatically
      discarded. An estimate of plaque type is also given. Finally, 3D reconstruction
      of all detected regions is made. The suitability of this methodology has been
      verified for the analysis and visualization of plaque length, stenosis severity,
      automatic detection of the most problematic regions, calculus of plaque volumes
      and a preliminary estimation of plaque type obtaining for automatic measures of
      lumen and vessel area an average error smaller than 1mm(2) (equivalent
      aproximately to 10% of the average measure), for calculus of plaque and lumen
      volume errors smaller than 0.5mm(3) (equivalent approximately to 20% of the
      average measure) and for plaque type estimates a mismatch of less than 8% in the
      analysed frames.

PMID- 17215104
TI  - Regulation of phosphoinositide 3-kinase signaling by oxidants: hydrogen peroxide
      selectively enhances immunoreceptor-induced recruitment of phosphatidylinositol
      (3,4) bisphosphate-binding PH domain proteins.
AB  - Phosphoinositide 3-kinases (PI3Ks) generate several distinct lipid second
      messengers including phosphatidylinositol (3,4,5) trisphosphate (PIP3) and
      phosphatidylinositol (3,4) bisphosphate PI(3,4)P2. PI(3,4)P2 is produced with
      distinct kinetics and binds to distinct PH domain effector proteins; however, the
      regulation of this signaling pathway is poorly understood. Superoxides such as
      hydrogen peroxide are transiently produced after activation through various cell
      surface receptors and play important roles in immune and inflammatory responses.
      Here we use quantitative microscopy to examine the effect of peroxide on
      PI(3,4)P2-mediated mobilization of signaling proteins in B lymphocytes. Peroxide
      was found to induce dose-dependant membrane recruitment of the PI(3,4)P2-binding
      PH domain proteins Bam32, TAPP2 and Akt/PKB but not the PIP3-binding PH domain of
      Btk. Peroxide-induced membrane recruitment was found to be dependant on PI3K
      activity, with the p110delta isoform contributing much of the activity in the
      BJAB human B lymphoma model. Strikingly, peroxide co-stimulation enhanced antigen
      receptor-induced membrane recruitment of Bam32 and TAPP2, with combined
      stimulation exceeding the maximum achievable with either stimulus alone.
      Expression of the lipid phosphatase PTEN led to reduction of antigen receptor
      induced membrane recruitment of TAPP2; however, peroxide costimulation could
      overcome the inhibitory effect of PTEN. Inhibition of the NADPH oxidase led to
      reduction of antigen receptor-induced membrane recruitment of TAPP2. Our results
      indicate that exogenous and endogenous superoxides can modulate the quality of
      the PI3K signal in lymphocytes by selectively increasing PI(3,4)P2-dependant
      signaling.

PMID- 17215105
TI  - Delayed transactivation of the receptor for nerve growth factor is required for
      sustained signaling and differentiation by alpha2-adrenergic receptors in
      transfected PC12 cells.
AB  - Alpha2-adrenergic receptors have been reported to induce subtype-specific
      neuronal differentiation in vitro, but the signaling mechanisms that mediate this
      effect have not been characterized. In the present study we found that stimulated
      alpha2-ARs induce delayed transactivation of TrkA in PC12 cells. The
      transactivation of TrkA was sensitive to the PP1 inhibitor of the Src family
      kinases and required prior transactivation of the EGF receptor. Moreover, alpha2
      adrenergic receptors induced sustained activation of MAPK and Akt. The sustained
      activation of Akt, but not of MAPK, was subtype-specific and correlated with the
      neuronal differentiation of PC12 cells, with the order alpha2A<alpha2B<alpha2C.
      Furthermore, stimulated alpha2-ARs induced an increased over time expression of
      the cell cycle associated proteins, p21WAF1 and Cyclin D1 and led to cell cycle
      arrest in a similar subtype-specific manner. Contrary to sustained activation of
      MAPK, the persistent activation of Akt and of p21WAF1 and Cyclin D1 as well as
      neurite outgrowth and expression of the neuronal marker peripherin, were all
      blocked by K252a an inhibitor of TrkA activity. Together these results
      demonstrate a novel outcome following alpha2-AR-mediated EGFR transactivation,
      being the consecutive transactivation of TrkA, and that this event may mediate
      the subtype-specific differentiation of alpha2-AR-expressing PC12 cells.

PMID- 17215106
TI  - Seizure prophylaxis in an animal model of epilepsy by dietary fluoxetine
      supplementation.
AB  - Clinical and animal model evidence suggests that selective serotonin reuptake
      inhibitors (SSRIs) act as anticonvulsants. The present studies tested the
      possibility that the El mouse model of genetically predisposed/handling-triggered
      epilepsy would exhibit fewer seizures following SSRI treatment via dietary
      fluoxetine adulteration. In particular, potential bioenergetic and neural
      mechanisms for anticonvulsant efficacy of fluoxetine were explored using food
      intake/body weight monitoring and quantification of brain serotonin transporter
      protein. El mice consuming a chow diet ad libitum or yoked in quantity to
      fluoxetine diet intake exhibited seizure incidence of 40% in response to tail
      suspension handling, whereas seizures were abolished (0%) among El mice consuming
      a fluoxetine-adultered diet over 7 days. A 3 day period of fluoxetine
      administration was insufficient to exert anticonvulsant efficacy and all
      treatment groups exhibited the same circadian locomotor activity patterns at the
      time of seizure susceptibility testing. Bioenergetic factors could not account
      for the anticonvulsant efficacy of fluoxetine since yoked diet controls with
      matched food intake, body weight change and blood glucose levels exhibited the
      same 40% seizure incidence as ad libitum chow controls. Importantly, the 7 day
      period of dietary fluoxetine exposure was effective in selectively reducing cell
      density in the parietal cortex and increasing serotonin transporter protein
      content in the nucleus accumbens. Taken together, these results suggest that
      dietary fluoxetine supplementation abolishes handling-induced seizure
      susceptibility in El mice via a neural remodeling mechanism independent of energy
      balance.

PMID- 17215107
TI  - Lack of evidence of an allelic association of a functional GABRB3 exon 1a
      promoter polymorphism with idiopathic generalized epilepsy.
AB  - PURPOSE: Mutation screening and linkage disequilibrium mapping of the gene
      encoding the GABA(A) beta(3) subunit (GABRB3) identified a common genetic variant
      in the exon 1a promoter region (C-allele of rs4906902) which displayed a reduced
      transcriptional activity and showed a strong allelic association with childhood
      absence epilepsy (CAE). The present population-based association study tested
      whether the C-allele of rs4906902 confers susceptibility to CAE or other common
      syndromes of idiopathic generalized epilepsy (IGE) in a German sample. METHODS:
      Seven hundred and eighty unrelated German IGE patients (250 CAE, 123 juvenile
      absence epilepsy, 303 juvenile myoclonic epilepsy (JME), 104 epilepsy with
      generalized tonic-clonic seizures on awakening) and 559 healthy population
      controls were genotyped for the single nucleotide polymorphism (SNP) rs4906902.
      RESULTS: The frequency of the risk-conferring C-allele did not differ
      significantly between CAE patients (f(C)=0.190) and controls (f(C)=0.183;
      P=0.376, one-tailed). Similarly, no evidence for an allelic association was found
      for 373 patients with idiopathic absence epilepsy, 303 JME patients, and the
      entire IGE sample (P>0.77, two-tailed). CONCLUSION: Our study failed to replicate
      an association of the common GABRB3 exon 1a promoter SNP rs4906902 with CAE.
      Moreover, the present results do not provide evidence that the common functional
      C-variant confers a substantial epileptogenic effect to a broad spectrum of IGE
      syndromes in the German population.

PMID- 17215108
TI  - A cognitive bias against disconfirmatory evidence (BADE) is associated with
      schizotypy.
AB  - A bias against disconfirmatory evidence (BADE) has been observed in
      schizophrenia, and in the present study we evaluated whether this extends to a
      nonclinical sample scoring high on a schizotypy scale. Thirty-seven high and 32
      low schizotypy healthy participants were sequentially presented with three
      sentences that increasingly disambiguated the true content of a delusion-neutral
      scenario and were asked to rate the plausibility of four interpretations for this
      scenario. Relative to low schizotypy participants, high schizotypy participants
      continued to endorse their initial beliefs, even in the face of evidence that
      disconfirmed these beliefs. This result provides support for the "schizophrenia
      spectrum" account of psychosis.

PMID- 17215109
TI  - Insight in individuals with an At Risk Mental State.
AB  - PURPOSE: On average, people with an At Risk Mental State (ARMS) for psychosis are
      more willing to seek and accept clinical help than patients with psychotic
      disorders, suggesting that insight in this group is relatively less impaired. We
      compared the level and quality of insight in the ARMS and in first episode
      psychosis. MATERIALS AND METHODS: Insight about illness was assessed in subjects
      with an ARMS and in patients with first episode psychosis (FEP) who were and were
      not help-seeking, using the Schedule for Assessment of Insight (SAI-E). RESULTS:
      Insight was impaired in ARMS subjects, but there was considerable variability in
      the insight displayed between subjects. Compared to FEP subjects, ARMS subjects
      showed greater insight, particularly with respect to Symptom Relabelling. ARMS
      subjects were more likely to interpret anomalous experiences as symptoms of
      illness, and to perceive themselves as needing treatment. CONCLUSIONS: Insight in
      people at high risk for psychosis is impaired, despite the fact that they are
      help-seeking. Insight varies between subjects, highlighting the need to
      comprehensively assess all aspects of insight in those with an ARMS. ARMS
      subjects are impaired in their ability to appraise anomalous experiences as
      symptoms of illness, but much less impaired than FEP subjects. This is consistent
      with cognitive models that propose that the way symptoms are appraised determines
      whether the individual develops a psychotic illness.

PMID- 17215110
TI  - In vivo optical coherence tomography of basal cell carcinoma.
AB  - BACKGROUND: Optical coherence tomography (OCT) is a promising non-invasive
      imaging technique that has not systematically been studied in skin cancer such as
      basal cell carcinoma (BCC). OBJECTIVE: We aimed, first, to describe the in vivo
      histologic features of BCC by using OCT, and second, to find out whether it is
      possible to differentiate BCC subtypes by means of OCT. METHODS: Prior to the
      excision, the BCCs (n=43) as well as adjacent non-lesional skin sites were
      assessed by OCT in vivo. The lesional area of interest was marked prior to OCT
      and tattooed after excision, respectively, in order to enable topographical
      concordance between the cross-sectional OCT images and the histologic sections.
      RESULTS: Compared to non-lesional skin, a loss of normal skin architecture and
      disarrangement of the epidermis and upper dermis was observed in the OCT images
      of BCCs. Features that were frequently identified by OCT and correlated with
      histology included large plug-like signal-intense structures, honeycomb-like
      signal-free structures, and prominent signal free cavities in the upper dermis.
      With regard to the aforementioned OCT features, no statistically significant
      (P<0.05) difference was found between nodular, multifocal superficial, and
      infiltrative BCCs, respectively. CONCLUSIONS: OCT is capable to visualize altered
      skin architecture and histopathological correlates of BCC. However, there is not
      at this time sufficient data supporting the clinical use of OCT for the
      differentiation of BCC subtypes.

PMID- 17215112
TI  - [Advantages and drawbacks of in vitro Interferon-gamma/T cell assays compared to
      the Mantoux test for the diagnosis of tuberculosis].
AB  - The development of in vitro blood tests that measure the delayed hypersensitivity
      reaction developed after contact with Mycobacterium tuberculosis will change
      progressively the diagnosis of M. tuberculosis infection. These blood assays
      (Quantiferon TB Gold, Cellestis, Australia; T-SPOT.TB, Oxford Immunotec, United
      Kingdom) use specific, complex M. tuberculosis antigens (ESAT-6 and CFP-10),
      whereas the intra-dermal Mantoux test is done with tuberculin, a complex mixture
      of more than 200 antigens. ESAT-6 and CFP-10 are absent from all the BCG vaccine
      strains used throughout the world. Significant improvement in the specificity
      with equivalent or increased sensitivity of the in vitro tests compared to the
      Mantoux test will lead eventually to replacement of the latter.

PMID- 17215111
TI  - Focal adhesions regulate Abeta signaling and cell death in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that results from a loss
      of synaptic transmission and ultimately cell death. The presenting pathology of
      AD includes neuritic plaques composed of beta-amyloid peptide (Abeta) and
      neurofibrillary tangles composed of hyperphosphorylated tau, with neuronal loss
      in specific brain regions. However, the mechanisms that induce neuronal cell loss
      remain elusive. Focal adhesion (FA) proteins assemble into intracellular
      complexes involved in integrin-mediated communication between the extracellular
      matrix and the actin cytoskeleton, regulating many cell physiological processes
      including the cell cycle. Interestingly, recent studies report that integrins
      bind to Abeta fibrils, mediating Abeta signal transmission from extracellular
      sites of Abeta deposits into the cell and ultimately to the nucleus. In this
      review, we will discuss the Abeta induced integrin/FA signaling pathways that
      mediate cell cycle activation and cell death.

PMID- 17215113
TI  - Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following
      oral administration in rats.
AB  - This study investigated the pharmacokinetic properties of crocin following oral
      administration in rats. After a single oral dose, crocin was undetected while
      crocetin, a metabolite of crocin, was found in plasma at low concentrations.
      Simultaneously, crocin was largely present in feces and intestinal contents
      within 24h. After repeated oral doses for 6 days, crocin remained undetected in
      plasma and plasma crocetin concentrations were comparable to the corresponding
      data obtained after the single oral dose. Furthermore, the absorption
      characteristics of crocin were evaluated in situ using an intestinal
      recirculation perfusion method. During recirculation, crocin was undetected and
      low concentrations of crocetin were detected in plasma. The concentrations of
      crocin in the perfusate were reduced through different intestinal segments, and
      the quantities of drug lost were greater throughout the colon. These results
      indicate that (1) orally administered crocin is not absorbed either after a
      single dose or repeated doses, (2) crocin is excreted largely through the
      intestinal tract following oral administration, (3) plasma crocetin
      concentrations do not tend to accumulate with repeated oral doses of crocin, and
      (4) the intestinal tract serves as an important site for crocin hydrolysis.

PMID- 17215114
TI  - Content comparison of health-related quality of life instruments for COPD.
AB  - BACKGROUND: Due to the increasing importance of quality of life assessments in
      chronic obstructive pulmonary disease (COPD) patients, and the increased use of
      the International Classification of Functioning, Disability and Health (ICF) for
      comparative purposes it is essential to understand the relationship between
      health-related quality of life (HRQL) instruments and the ICF. OBJECTIVE: The
      objective of this study was to compare the content of recommended COPD-specific
      HRQL instruments using the ICF as reference. COPD-specific instruments mentioned
      in widely accepted guidelines were linked to the ICF using standardized linking
      rules. The degree of agreement between various health professionals was assessed
      by calculating the kappa statistic. RESULTS: Eleven instruments were included.
      They varied strongly in the number of concepts contained and the number of ICF
      categories used to map these concepts. A total of 548 concepts were identified
      and linked to 60 different ICF categories. Only the single category 'dyspnea' was
      covered by all instruments, whilst 21 categories were unique to specific
      instruments. The relationships of the measures with the ICF were identified.
      CONCLUSIONS: This study may aid researchers and clinicians to choose the most
      appropriate instrument for a specific purpose as well as help compare studies
      that have used different instruments for HRQL assessment.

PMID- 17215115
TI  - Effects of topical formoterol alone and in combination with budesonide in a
      pollen season model of allergic rhinitis.
AB  - BACKGROUND: beta(2)-Agonists may exert mast cell stabilizing and anti-plasma
      exudation effects. While available data suggest no or only marginal effects of
      beta(2)-agonists on symptoms of allergic rhinitis, little is known about whether
      these drugs may add to the efficacy of anti-rhinitis drugs. OBJECTIVE: To examine
      effects of a beta(2)-agonist, alone and in combination with an intranasal
      glucocorticosteroid, on symptoms and signs of allergic rhinitis. METHODS:
      Patients were examined in a pollen season model. Budesonide 64 microg, alone and
      in combination with formoterol 9 microg, as well as formoterol 9 microg alone was
      given in a placebo-controlled and crossover design. After 7 days of treatment,
      the patients received allergen challenges for 7 days. Symptoms and nasal peak
      inspiratory flow (PIF) were recorded. Nasal lavages with and without histamine
      were carried out at the end of each challenge series. These lavages were analysed
      for tryptase, eosinophil cationic protein (ECP), and alpha(2)-macroglobulin as
      indices of mast cell activity, eosinophil activity, and plasma exudation,
      respectively. RESULTS: Budesonide reduced symptoms of allergic rhinitis and
      improved nasal PIF in the morning, in the evening as well as post allergen
      challenge. Formoterol alone did not affect symptoms or nasal PIF and did not
      affect the efficacy of budesonide. Tryptase, ECP, and alpha(2)-macroglobulin were
      significantly reduced by budesonide. Formoterol alone did not affect these
      indices and did not affect the anti-inflammatory effect of budesonide.
      CONCLUSION: The present dose of formoterol does not affect symptoms and
      inflammatory signs of allergic rhinitis and does not add to the efficacy of
      topical budesonide.

PMID- 17215116
TI  - Multianalyte immunoassay based on insulating-controllable PoPD film at arrayed
      electrodes integrated on a silicon chip.
AB  - A novel, simple and label-free multianalyte immunoassay system is presented here
      by integrating arrayed electrodes on a silicon chip via MEMS. The chip is
      consisted of six Au disk electrodes, an Au counter electrode and an Ag/AgCl
      reference electrode. Semi-insulating poly(o-phenylenediamine) (PoPD) was utilized
      to co-polymerize and immobilize antibodies at the arrayed Au electrodes, and
      wider linear detection range was obtained than those prepared with completely
      insulating PoPD. Electrochemical cyclic voltammogram (CV), AC impedance
      spectroscopy, AFM and fluorescence microscopy were employed to characterize the
      system. The arrayed electrodes offered exact control of deposition position via
      electrochemical operation, allowing selectively immobilization of different
      antibodies at desired positions on a single chip. Specific recognition of
      antibody (Ab) to corresponding antigen (An) was quantitatively monitored by
      cyclic voltammograms in the presence of electrochemical redox probe, ferrocene
      methanol. The proposed immunoassay chips showed sensitive response to three liver
      fibrosis markers, hyaluronic acid (HA), collagen type IV (IV-C) and lamin (LN) at
      ng/mL level simultaneously and specifically in a tiny amount of volume, usually
      50 microL. The results obtained via chips were well consistent with those
      obtained by commercial radio immunoassays (RIA).

PMID- 17215117
TI  - Glucose biosensor based on immobilization of glucose oxidase in poly(o
      aminophenol) film on polypyrrole-Pt nanocomposite modified glassy carbon
      electrode.
AB  - Novel Pt nanoclusters embedded polypyrrole nanowires (PPy-Pt) composite was
      electrosynthesized on a glassy carbon electrode, denoted as PPy-Pt/GCE. A glucose
      biosensor was further fabricated based on immobilization of glucose oxidase (GOD)
      in an electropolymerized non-conducting poly(o-aminophenol) (POAP) film that was
      deposited on the PPy-Pt/GCE. The morphologies of the PPy nanowires and PPy-Pt
      nanocomposite were characterized by field emission scanning electron microscope
      (FE-SEM). Effect of experimental conditions involving the cycle numbers for POAP
      deposition and Pt nanoclusters deposition, applied potential used in glucose
      determination, temperature and pH value of the detection solution were
      investigated for optimization. The biosensor exhibited an excellent current
      response to glucose over a wide linear range from 1.5 x 10(-6) to 1.3 x 10(-2)M
      (r=0.9982) with a detection limit of 4.5 x 10(-7)M (s/n=3). Based on the
      combination of permselectivity of the POAP and the PPy films, the sensor had good
      anti-interference ability to ascorbic acid (AA), uric acid (UA) and
      acetaminophen. The apparent Michaelis-Menten constant (K(m)) and the maximum
      current density (I(m)) were estimated to be 23.9 mM and 378 microA/cm(2),
      respectively. In addition, the biosensor had also good sensitivity, stability and
      reproducibility.

PMID- 17215118
TI  - The Sonogel-Carbon materials as basis for development of enzyme biosensors for
      phenols and polyphenols monitoring: a detailed comparative study of three
      immobilization matrixes.
AB  - Three amperometric biosensors based on immobilization of tyrosinase on a new
      Sonogel-Carbon electrode for detection of phenols and polyphenols are described.
      The electrode was prepared using high energy ultrasounds (HEU) directly applied
      to the precursors. The first biosensor was obtained by simple adsorption of the
      enzyme on the Sonogel-Carbon electrode. The second and the third ones, presenting
      sandwich configurations, were initially prepared by adsorption of the enzyme and
      then modification by mean of polymeric membrane such as polyethylene glycol for
      the second one, and the ion-exchanger Nafion in the case of the third biosensor.
      The optimal enzyme loading and polymer concentration, in the second layer, were
      found to be 285 U and 0.5%, respectively. All biosensors showed optimal activity
      at the following conditions: pH 7, -200 mV, and 0.02 mol l(-1) phosphate buffer.
      The response of the biosensors toward five simple phenols derivatives and two
      polyphenols were investigated. It was found that the three developed tyrosinase
      Sonogel-Carbon based biosensors are in satisfactory competitiveness for phenolic
      compounds determination with other tyrosinase based biosensors reported in the
      literature. The detection limit, sensitivity, and the apparent Michaelis-Menten
      constant K(m)(app) for the Nafion modified biosensor were, respectively, 0.064,
      0.096, and 0.03 micromol, 82.5, 63.4, and 194 nA micromol(-1)l(-1), and 67.1,
      54.6, and 12.1 micromol l(-1) for catechol, phenol, and 4-chloro-3-methylphenol.
      Hill coefficient values (around 1 for all cases), demonstrated that the
      immobilization method does not affect the nature of the enzyme and confirms the
      biocompatibility of the Sonogel-Carbon with the bioprobe. An exploratory
      application to real samples such as beers, river waters and tannery wastewaters
      showed the ability of the developed Nafion/tyrosinase/Sonogel-Carbon biosensor to
      retain its stable and reproducible response.

PMID- 17215119
TI  - Sensitive estimation of total cholesterol in blood using Au nanowires based micro
      fluidic platform.
AB  - Determination of cholesterol level in blood is important in clinical
      applications. In this work, modified Au nanowires-electrochemical biosensor based
      on MEMS micro-fluidic platform is proposed for estimating total cholesterol in
      blood. This sensor consists of "aligned" Au nanowires as working electrode,
      platinum counter electrode deposited on the silicon platform and Ag/AgCl (3M KCl)
      reference electrode. The "aligned" Au nanowires are immobilized with cholesterol
      oxidase and cholesterol esterase using specific covalent chemistry. Further, Au
      nanowires promotes better electron transfer between the enzymes and electrodes,
      because of their large surface to volume ratio, small diffusion time, large
      electrical conductivity and their aligned nature. The modified Au nanowires
      showed a stable calibration line and a quasi-linear relationship between
      cholesterol level and current response in the range of 1-6 mM (in steps of 1 mM
      over the baseline blood serum). The sensitivity of the modified electrode was
      found to be about 69 nA/mM with good storage and interference stability.

PMID- 17215121
TI  - Expression of p53 isoforms in squamous cell carcinoma of the head and neck.
AB  - Recent data indicate that, similar to p63 and p73, several different p53 isoforms
      can be produced in humans through alternative initiation of translation, usage of
      an internal promoter and alternative splicing. These isoforms are reported to
      have varying functions and expressions. In squamous cell carcinoma of the head
      and neck (SCCHN), disruption of the p53 pathway is one of the most common genetic
      alterations. However, to our knowledge, no studies regarding the expression of
      different p53 isoforms in SCCHN have so far been performed. We screened for the
      expression of different p53 isoforms in SCCHN and clinically normal oral
      epithelia using nested RT-PCR. p53 mRNA was expressed in all tumours, all matched
      clinically normal tissue adjacent to the tumour and in buccal mucosa from healthy
      volunteers. Of the novel isoforms, p53beta was detected in the majority of
      samples analysed, and all of the recently described isoforms were also detected
      in at least some tumour and normal epithelium samples, with the exception of
      Deltap53 isoforms. We conclude that p53 variant mRNAs are expressed in both
      normal oral stratified epithelium and SCCHN. Improvements in methodologies and
      reagents to detect and quantify p53 isoform expression in clinical material will
      be required to correlate p53 status with clinical outcomes.

PMID- 17215122
TI  - Effects of diet and exercise on plasma vitamin D (25(OH)D) levels in Vietnamese
      immigrant elderly in Sydney, Australia.
AB  - Vitamin D deficiency may be associated with osteoporosis and fractures in the
      elderly. In Australia where there is a sizeable Vietnamese population, research
      has not yet clarified the roles of diet, exercise and sun exposure in determining
      vitamin D status. Plasma samples for 25-hydroxy-vitamin D (25(OH)D); dietary
      intake of vitamin D and calcium; muscle strength and sun exposure were measured
      and weekly dairy intake, exercise levels and smoking habits were surveyed in free
      living elderly of Vietnamese and Australian/British origin. There was marginal
      vitamin D deficiency (<37 nmol/L 25(OH)D) in 63% of Vietnamese but only in 37% of
      Australian/British born. Low dairy intake and no vigorous exercise were best
      predictors of vitamin D deficiency in Vietnamese, taking into account age,
      gender, dietary intake and sun exposure. Since these migrant elderly may not get
      adequate sun exposure due to either clothing customs or cultural norms that
      encourage fair (untanned) skin, it is important to encourage increased exercise
      and dairy intake.

PMID- 17215123
TI  - Cloning, characterization and phylogenetic relationships of stxI, a endoxylanase
      encoding gene from Streptomyces thermonitrificans NTU-88.
AB  - A thermostable xylanase gene (stxI) obtained from Streptomyces thermonitrificans
      NTU-88 on domain analysis revealed an N-terminal catalytic domain featuring
      homology to a known xylanase within the glycoside hydrolase family 11.
      Recombinant STXI retained more than 60% of its activity following its incubation
      for at 60 degrees C for 24h. These characteristics were close to thermophile and
      mesophile Streptomyces strains. The main hydrolysis products of xylan degraded by
      STXI included large xylooligosaccharide fragments. These results indicated that
      STXI was a typical endoxylanase. As regards the phylogenetic relationships of
      GH11, STXI and the other xylanase deriving from Streptomyces were included in a
      subgroup of the aerobic bacterial group. This result implied that the
      evolutionary relationships between the various xylanases deriving from
      Streptomyces strains were convergent.

PMID- 17215124
TI  - Volatilization of ammonia from manure as affected by manure additives,
      temperature and mixing.
AB  - Ammonia (NH(3)) volatilization decreases the N-nutrient value of livestock manure
      slurries and can lead to soil acidification and eutrophication problems. In this
      study the effect of three manure additives (Euro Mest-mix (Mx), Effective Micro
      organisms (EM), and Agri-mest (Am)) on NH(3) volatilization at three temperatures
      (4, 20, and 35 degrees C) was investigated. The manufacturers claim that Mx
      contains absorbing clay minerals and that applying Am and EM to slurry will
      reduce nitrogen losses, most likely by enhancing the biodegradation of manure
      slurry. Furthermore, the effect of mixing slurry on NH(3) volatilization has been
      investigated. Ammonia volatilization increased with increasing temperature and
      mixing of the slurries. However, at 35 degrees C mixing of manure reduced NH(3)
      emissions compared to non-mixing, which is related to a reduced crust resistance
      to gaseous transport at higher temperatures for non-mixing. Moreover, mixing
      introduces oxygen into the anaerobic slurry environment which will slow down
      microbial activity. The use of additives did not change manure characteristics
      (pH, dry matter, N(total), N(mineral), C/N, and C/N(organic)) and did not result
      in a significant (p<0.05) decrease in NH(3) emissions, except that at 4 degrees C
      and no mixing a significant decrease of 34% in NH(3) volatilization was observed,
      when Am and EM together, were applied to slurry.

PMID- 17215125
TI  - Molecular biology of PCSK9: its role in LDL metabolism.
AB  - Proprotein convertase subtilisin-like kexin type 9 (PCSK9) is a newly discovered
      serine protease that destroys low density lipoprotein (LDL) receptors in liver
      and thereby controls the level of LDL in plasma. Mutations that increase PCSK9
      activity cause hypercholesterolemia and coronary heart disease (CHD); mutations
      that inactivate PCSK9 have the opposite effect, lowering LDL levels and reducing
      CHD. Although the mechanism of PCSK9 action is not yet clear, the protease
      provides a new therapeutic target to lower plasma levels of LDL and prevent CHD.

PMID- 17215126
TI  - Gender differences in knee kinematics and muscle activity during single limb drop
      landing.
AB  - The likelihood of sustaining an ACL injury in a noncontact situation is two to
      eight times greater for females than for males. However, the mechanism and risk
      factors of ACL injury are still unknown. We compared knee kinematics as well as
      electromyographic activity during landing between male and female athletes.
      Eighteen male athletes and nineteen female athletes participated in the
      experiment. The angular displacements of flexion/extension, valgus/varus, and
      internal/external tibial rotation, as well as the translational displacements of
      anterior/posterior tibial translation during single limb drop landing were
      calculated. Simultaneous electromyographical activity of the rectus femoris (RF)
      and hamstrings (Ham) was taken. During landing, internal tibial rotation of the
      females was significantly larger than that of the males, while differences were
      not observed in flexion, varus, valgus, and anterior tibial translation.
      Hamstrings/quadriceps ratio (HQR) for the 50 ms time period before foot contact
      was greater in males than in females. The mechanism of noncontact ACL injury
      during a single limb drop landing would be internal tibial rotation combined with
      valgus rotation of the knee. Increased internal tibial rotation combined with
      greater quadriceps activity and a low HQR could be one reason female athletes
      have a higher incidence of noncontact ACL injuries.

PMID- 17215128
TI  - 2(S)-(Cycloalk-1-enecarbonyl)-1-(4-phenyl-butanoyl)pyrrolidines and 2(S)-(aroyl)
      1-(4-phenylbutanoyl)pyrrolidines as prolyl oligopeptidase inhibitors.
AB  - In order to replace the P2-P1 amide group, different 1-cycloalkenyls and 2-aryls
      were studied in the place of the P1 pyrrolidine group of a 4-phenylbutanoyl-L-Pro
      pyrrolidine structure, which is a well-known prolyl oligopeptidase inhibitor SUAM
      1221. The 1-cyclopentenyl and the 2-thienyl groups gave novel compounds, which
      were equipotent with the corresponding pyrrolidine-analog SUAM-1221. It was shown
      that the P2-P1 amide group of POP inhibitors can be replaced by an alpha,beta
      unsaturated carbonyl group or the aryl conjugated carbonyl group.

PMID- 17215127
TI  - Crystal structure of the PXR-T1317 complex provides a scaffold to examine the
      potential for receptor antagonism.
AB  - The human pregnane X receptor (PXR) recognizes a range of structurally and
      chemically distinct ligands and plays a key role in regulating the expression of
      protective gene products involved in the metabolism and excretion of potentially
      harmful compounds. The identification and development of PXR antagonists is
      desirable as a potential way to control the up-regulation of drug metabolism
      pathways during the therapeutic treatment of disease. We present the 2.8A
      resolution crystal structure of the PXR ligand binding domain (LBD) in complex
      with T0901317 (T1317), which is also an agonist of another member of the orphan
      class of the nuclear receptor superfamily, the liver X receptor (LXR). In spite
      of differences in the size and shape of the receptors' ligand binding pockets,
      key interactions with this ligand are conserved between human PXR and human LXR.
      Based on the PXR-T1317 structure, analogues of T1317 were generated with the goal
      of designing an PXR antagonist effective via the receptor's ligand binding
      pocket. We find that selectivity in activating PXR versus LXR was achieved; such
      compounds may be useful in addressing neurodegenerative diseases like Niemann
      Pick C. We were not successful, however, in producing a PXR antagonist. Based on
      these observations, we conclude that the generation of PXR antagonists targeted
      to the ligand binding pocket may be difficult due to the promiscuity and
      structural conformability of this xenobiotic sensor.

PMID- 17215129
TI  - Radioactivity levels of recent sediments in the Butrint Lagoon and the adjacent
      coast of Albania.
AB  - Sediment samples have been collected in the Butrint area, located in the south
      west Albania to determine the radioactivity levels of (40)K, (137)Cs, (212)Bi,
      (212)Pb, (214)Bi, (214)Pb, (226)Ra and (228)Ac on the bed of the lagoon and
      adjacent sea, using direct counting gamma spectroscopy. The concentration of
      (137)Cs and (40)K varied from 2.8 to 37.5 Bq/kg and from 266 to 675 Bq/kg dry
      weight (dw), respectively (central values). The average concentrations of (238)U
      and (232)Th daughter products varied from 8 to 27 Bq/kg and from 13 to 40 Bq/kg
      dw, respectively. The measured (235)U activity ranged from 0.7 to 2.5 Bq/kg dw.
      Samples of different sedimentary properties, studied for the radioactivity
      concentration, revealed an inversely proportional relation between grain size and
      a linear combination of measured specific activities of (226)Ra, (232)Th
      ((228)Ac, (212)Bi and (212)Pb), (40)K and (137)Cs.

PMID- 17215130
TI  - Aortic translocation for the management of transposition of the great arteries
      with a ventricular septal defect, pulmonary stenosis, and hypoplasia of the right
      ventricle.
AB  - A 2-month-old patient with transposition of the great arteries, a ventricular
      septal defect, pulmonary stenosis, and severe hypoplasia of the right ventricle
      successfully underwent a biventricular repair utilizing the aortic translocation
      technique. Advantages of this surgical repair over the Rastelli procedure in the
      management of this complex congenital heart lesion are discussed.

PMID- 17215131
TI  - Can spontaneous pneumothorax patients be treated by ambulatory care management?
AB  - OBJECTIVE: In the Emergency Department, it would be worthwhile to treat
      pneumothorax patients on an outpatient basis by utilizing a small-calibre
      catheter and Heimlich valve insertion. We evaluated this treatment and compared
      it with the closed thoracostomy. METHODS: In this comparative study, the success
      rate, complications and recurrence rate of treating spontaneous pneumothorax
      patients by using a small-calibre catheter and Heimlch valve were compared with
      those of a similar-sized group treated by closed thoracostomy. RESULTS:
      Pneumothorax was successfully treated on an ambulatory basis by using the small
      calibre catheter and Heimlch valve in 20 patients (47%); this was less than the
      42 patients (89%) who were successfully treated by closed thoracostomy. While no
      complications were encountered in the group treated using the small-calibre
      catheter and Heimlich valve, 11 patients in the group treated by closed
      thoracostomy developed complications. The medical expenses for the treatment
      involving the small-calibre catheter and Heimlich valve were less than those for
      closed thoracostomy. CONCLUSION: Prior to the treatment, the patients should be
      fully informed of the success rate of this treatment and the possibility of
      requiring closed thoracostomy in the event of treatment failure.

PMID- 17215132
TI  - Surgical outcomes in the treatment of patients with tetralogy of Fallot and
      absent pulmonary valve.
AB  - OBJECTIVE: Tetralogy of Fallot and absent pulmonary valve (TOF/APV) is associated
      with significant pulmonary artery dilatation and airway compression. Treatment of
      infants presenting with respiratory symptoms early in life is associated with
      high mortality (20-60%). We aim to report our results and identify factors
      associated with survival and prolonged ventilation. METHODS: We performed a
      retrospective review of 62 consecutive patients following repair of TOF/APV (1982
      2006). Median age at repair was 1.4 years (1 day-35 years). Twenty patients
      required preoperative intubation. RESULTS: Sixty-one patients underwent complete
      repair. Thirty-three patients underwent pulmonary artery plication (n=15) or
      reduction (n=18). The right ventricular outflow tract (RVOT) was reconstructed
      with valved conduit (n=31), bioprosthetic valve (n=18), monocusp (n=8), or
      transannular patch (n=4). There were three perioperative and five late deaths.
      All perioperative deaths were in neonates and before 1995. Five- and ten-year
      survival was 93+/-4% and 87+/-5%. Mean ventilatory requirements for neonates,
      infants, and children > or =1 year were 36+/-35, 8+/-8, and 2.6+/-2.4 days
      (p<0.0001). On multivariable analysis, significant factors associated with
      prolonged ventilation were neonates (p<0.0001) and preoperative mechanical
      ventilation (p=0.088). Eight airway reinterventions were needed in seven infants
      with persistent postoperative airway compromise, pulmonary artery suspension
      (n=4), innominate artery suspension (n=2), and lobectomy (n=2). Freedom from RVOT
      reoperation was 89+/-5% and 59+/-9% at 5 and 10 years. There were no significant
      risk factors for time-related survival or RVOT reoperation on multivariable
      analysis. CONCLUSIONS: In contrast to children and adults with TOF/APV, neonates
      and small infants presenting with respiratory symptoms require prolonged
      ventilation and additional reinterventions for airway compression. Our current
      surgical approach which includes reduction and suspension of pulmonary arteries,
      reconstruction of a competent RVOT, and aggressive postoperative ventilatory
      management to relieve airway obstruction offers satisfactory outcomes.

PMID- 17215133
TI  - Analysis of the inflammatory response in endovascular treatment of aortic
      aneurysms.
AB  - OBJECTIVE: The objective of this study is to evaluate the inflammatory response
      caused by endovascular stents in the treatment of aortic aneurysms. METHODS:
      Twenty-five patients underwent endovascular stent treatment from March through
      December 2005. The evolution of mediators (sedimentation velocity, C reactive
      protein, interleukin-6, interleukin-8, tumor necrosis factor-alpha, intercellular
      adhesion molecule-1, l-selectin), inflammatory cells (leukocytes, lymphocytes,
      platelets), serum creatinine and body temperature within preoperative period and
      in the following postoperative periods--1, 6, 24 and 48 h, 7 days, 1-3 months,
      was analyzed. In order to achieve statistic significance, Friedman test and
      Wilcoxon test were used, with index of significance of 5% (p<0.05). RESULTS: Peak
      values of sedimentation velocity, C reactive protein and interleukin-6 were
      observed at 7 days (p<0.0001), 48 h (p<0.0001) and 24h (p<0.0001), respectively.
      Tumor necrosis factor-alpha and interleukin-8 did not show statistically
      significant variability during the entire follow-up. In terms of intercellular
      adhesion molecule-1 and l-selectin, their expressive values were found in late
      phase of follow-up, although without statistical significance. Elevation of
      leukocytes count occurred in premature phase of follow-up (p<0.0001), while
      lymphocyte and platelet count occurred in a late phase of follow-up (p<0.0001).
      Serum levels of creatinine did not show significant variability during follow-up.
      The period between 24 and 48 h corresponded to major frequency for fever
      (p<0.0001). CONCLUSION: Individual mediators analysis and inflammatory cells
      demonstrated variability of their values during postoperative follow-up. This
      could help in the analysis of the inflammatory response evolution caused by
      endovascular stent treatment for aortic aneurysms in premature and late phases
      after implantation of the vascular prosthesis.

PMID- 17215134
TI  - Hydatid cyst involving the aortic arch.
AB  - We report a very rare case of primary mediastinal hydatid cyst which invaded the
      ascending aorta and the aortic arch which initially presented as a cranial mass.
      Aortic wall is a very unusual site for the hydatid cysts. To the best of our
      knowledge, this is the first reported case of hydatid cyst located within the
      aortic arch lumen. Patient underwent ascending aortic and hemiarch replacement
      under hypothermic circulatory arrest and removal of the cyst. Patient had an
      uneventful recovery and has been on follow-up. Although the literature data are
      very limited, we believe that the aortic procedure of choice should be graft
      interpositon rather than patch repair.

PMID- 17215135
TI  - Incidental radiological finding of tracheal diverticulum.

PMID- 17215136
TI  - Small size new silastic drains: life-threatening hypovolemic shock after thoracic
      surgery associated with a non-functioning chest tube.
AB  - We report a case of a massive haemothorax following bilateral surgical resection
      of apical bullae. Occult bleeding was not recognized until the onset of a life
      threatening circulatory collapse associated with metabolic acidosis and a fall in
      haemoglobin level. Using a thoracotomy, large amounts of blood were evacuated
      from the thoracic cavity and bleeding originating from ruptured pleural adhesion
      was easily controlled. Thrombotic material with talc particles was found to
      obstruct the 19-French 4-channel Blake drain. Although this new silastic Blake
      tube has been recommended in cardiac surgical patients, extending its indication
      in thoracic surgery, particularly when talc pleurodesis is used, should be
      questioned given the enhanced postoperative prothrombotic state and risk of drain
      obstruction. In conclusion, caution should be exercised when new small-sized
      material is introduced in clinical practice, especially after talc pleurodesis
      following thoracic surgery.

PMID- 17215137
TI  - A promoter element with enhancer properties, and the orphan nuclear receptor
      RORalpha, are required for Purkinje cell-specific expression of a Gi/o modulator.
AB  - The promoter and structural portion of the gene, Pcp-2(L7), has frequently been
      used to target expression of proteins to cerebellar Purkinje cells. In our
      continuing analysis of the transcription of this gene and how it relates to the G
      protein and Ca2+ channel modulatory functions of the encoded protein, we have
      dissociated the promoter and structural gene and identified cooperative
      functions. A 0.9 kb fragment of the proximal promoter has positional properties
      of a classical enhancer, yet its function requires the presence of the structural
      gene. We demonstrate that RORalpha, the gene product of the mutant mouse locus
      called staggerer (Rora(sg)), binds to and activates expression through this
      promoter element using functional assays in vitro and in vivo. The structural
      gene has a repressive effect on gene expression outside Purkinje cells, and
      likely participates in the suppression of Pcp-2(L7) gene expression in the many
      other brain and non-neuronal cell types, besides Purkinje cells, known to express
      RORalpha. Additional studies in vivo show that while Pcp-2(L7) expression is
      dependent on RORalpha throughout the cerebellum, this dependence is greatest in
      the intermediate region between the vermis and far lateral hemispheres. Thus, in
      addition to its recently indicated role in Ca2+-mediated reciprocal cell-cell
      signaling in Purkinje cells, RORalpha may also contribute to functional
      differences in cerebellar subregions.

PMID- 17215138
TI  - Coupling profile of the metabotropic glutamate receptor 1alpha is regulated by
      the C-terminal domain.
AB  - The metabotropic glutamate receptor 1alpha (mGluR1alpha) is known to cause
      various cell responses via coupling with different types of G protein. By using a
      combination of fluorescent indicators, we simultaneously observed the dual
      signals of mGluR1alpha, via activation of the Gq and Gs proteins, as increases in
      the intracellular Ca(2+) and cAMP concentration, respectively. The dual signals
      are regulated by long C-terminal domain of mGluR1alpha since a short splice
      variant, mGluR1beta, could not activate the Gs pathway. Cytoskeletal proteins
      that interact with the long C-terminal tail, such as homer1 and 4.1G, are known
      to modulate the mGluR1alpha signaling; however, their effects on the dual
      signaling remain unknown. The simultaneous monitoring demonstrated that the 4.1G
      behaves as a regulator of dual signaling rather than a simple inhibitor, via its
      interaction with a cluster of acidic residues in the distal C-tail, which locates
      close to the important regions for the Gs coupling.

PMID- 17215140
TI  - Over-expression, purification, and characterization of recombinant NAD-malic
      enzyme from Escherichia coli K12.
AB  - NAD(+)-dependent malic enzyme (NAD-ME) gene from Escherichia coli K12 was
      inserted into an expression vector pET24b(+) and transformed into E. coli BL21
      (DE3). Recombinant NAD-ME was expressed upon IPTG induction, purified with
      affinity chromatography, and biochemically characterized. The results showed that
      recombinant NAD-ME could be produced mainly in a soluble form. The monomeric
      molecular weight of recombinant NAD-ME was about 65 kDa, whereas monomer,
      homotetramer, and homooctamer were formed in solution as revealed by
      nondenaturing polyacrylamide gel electrophoresis analysis. Finally, the K(m)
      values of NAD-ME for L-malate and NAD were determined as 0.420+/-0.174 and
      0.097+/-0.038 mM, respectively, at pH 7.2. By using this over-expression and
      purification system, recombinant E. coli K12 NAD-ME can now be obtained in large
      quantity necessary for further biochemical characterization and applications.

PMID- 17215141
TI  - A new tagging system for production of recombinant proteins in Drosophila S2
      cells using the third domain of the urokinase receptor.
AB  - The use of protein fusion tag technology greatly facilitates detection,
      expression and purification of recombinant proteins, and the demands for new and
      more effective systems are therefore expanding. We have used a soluble truncated
      form of the third domain of the urokinase receptor as a convenient C-terminal
      fusion partner for various recombinant extracellular human proteins used in basic
      cancer research. The stability of this cystein-rich domain, which structure
      adopts a three-finger fold, provides an important asset for its applicability as
      a fusion tag for expression of recombinant proteins. Up to 20mg of intact fusion
      protein were expressed by stably transfected Drosophila S2 cells per liter of
      culture using this strategy. Purification of these secreted fusion proteins from
      the conditioned serum free medium of S2 cells was accompanied by an efficient one
      step immunoaffinity chromatography procedure using the immobilized anti-uPAR
      monoclonal antibody R2. An optional enterokinase cleavage site is included
      between the various recombinant proteins and the linker region of the tag, which
      enables generation of highly pure preparations of tag-free recombinant proteins.
      Using this system we successfully produced soluble and intact recombinant forms
      of extracellular proteins such as CD59, C4.4A and vitronectin, as well as a
      number of truncated domain constructs of these proteins. In conclusion, the
      present tagging system offers a convenient general method for the robust
      expression and efficient purification of a variety of recombinant proteins.

PMID- 17215139
TI  - ATP7A (Menkes protein) functions in axonal targeting and synaptogenesis.
AB  - Menkes disease (MD) is a neurodegenerative disorder caused by mutations in the
      copper transporter, ATP7A, a P-type ATPase. We previously used the olfactory
      system to demonstrate that ATP7A expression is developmentally, not constitutive,
      regulated, peaking during synaptogenesis when it is highly expressed in extending
      axons in a copper-independent manner. Although not known to be associated with
      axonal functions, we explored the possibility that the inability of mutant ATP7A
      to support axon outgrowth contributes to the neurodegeneration seen in MD. In
      vivo analysis of the olfactory system in mottled brindled (Atp7aMobr) mice, a
      rodent model for MD, demonstrates that ATP7A deficiency affects olfactory sensory
      neuron (OSN) maturation. Disrupted OSN axonal projections and mitral/tufted cell
      dendritic growth lead to altered synapse integrity and glomerular disorganization
      in the olfactory bulbs of Atp7aMobr mice. Our data indicate that the neuronal
      abnormalities observed in MD are a result of specific age-dependent developmental
      defects. This study demonstrates a role for ATP7A and/or copper in axon outgrowth
      and synaptogenesis, and will further help identify the cause of the
      neuropathology that characterizes MD.

PMID- 17215142
TI  - Heterosis of haemolymph analytes of two geographic populations in Chinese shrimp
      Fenneropenaeus chinensis.
AB  - Fenneropenaeus chinensis is distributed along the coasts of the northern seacoast
      of China and the Korean Peninsula. According to their migration routes, spawning
      and overwintering places, F. chinensis is divided mainly into three geographic
      variety populations. These populations represent potentially different genetic
      resources important to hybridisation breeding programs. To evaluate heterosis of
      the total protein concentration (PC), haemocyanin concentration (HC),
      penoloxidase (PO) activity, acid phosphatase (ACP) activity, alkaline phosphatase
      (ALP) activity and antimicrobial activity (Ua) mating was produced between and
      within Yellow and Bo sea (YB) population and southern seacoast of Korean
      Peninsula (SK) population, and the offspring of 49 families was reared to 7.64 g
      in the controlled environment. The results showed that the content of all
      haemolymph analytes of SK population was higher than that of YB population, and
      the immunocompetence in all hybridisations were higher than that in YB male x YB
      female except of HC in YB male x SK female. Nine of 12 hybridisations had
      manifested positive heterosis in six haemolymph analytes. Heterosis of SK x YB
      was all-positive, and this hybridisation was better than YB x SK in HC, PO, ALP
      activity and Ua. The results suggested that the haemolymph analytes of YB and SK
      populations had many genetic differences, and hybridisation was an important tool
      to increase immune reaction and adverse resistance.

PMID- 17215143
TI  - Assessment of upper extremity muscle function in persons with tetraplegia.
AB  - The objective was to investigate the actual level of muscle function impairment
      in tetraplegic persons and, inextricably related to this, the possibilities to
      compensate function loss using new muscle coalitions. In this cross-sectional
      group study, 20 persons with a cervical spinal cord injury (SCI) at segmental
      levels C5C6 or C7C8 and 10 control persons participated. Activity from 21 upper
      extremity and trunk muscles was recorded during standardised gross upper
      extremity task performance. No substantial differences in main activation
      patterns were found between C7C8 and control subjects. In contrast, main
      activation patterns in C5C6 persons showed an absence of selectivity, which may
      be explained by the participants activating every controllable muscle in an
      attempt to perform maximally. In order to identify more intricate differences in
      muscle activation between control and C7C8 persons a fine motor function task may
      be necessary. Muscle activation patterns during arm task performance were stable
      in all three groups.

PMID- 17215144
TI  - Auditory-visual multisensory interactions attenuate subsequent visual responses
      in humans.
AB  - Effects of multisensory interactions on how subsequent sensory inputs are
      processed remain poorly understood. We investigated whether multisensory
      interactions between rudimentary visual and auditory stimuli (flashes and beeps)
      affect later visual processing. A 2 x 3 design varied the number of flashes (1 or
      2) with the number of beeps (0, 1, or 2) presented on each trial, such that
      '2F1B' refers to the presentation of 2 flashes with 1 beep. Beeps, when present,
      were synchronous with the first flash, and pairs of stimuli within a trial were
      separated by 52 ms ISI. Subjects indicated the number of flashes presented.
      Electrical neuroimaging of 128-channel event-related potentials assessed both the
      electric field strength and topography. Isolation of responses a visual stimulus
      that was preceded by a multisensory event was achieved by calculating the
      difference between the 2F1B and 1F1B conditions, and responses to a visual
      stimulus preceded by a unisensory event were isolated by calculating the
      difference between the 2F0B and 1F0B conditions (MUL and VIS, respectively).
      Comparison of MUL and VIS revealed that the treatment of visual information was
      significantly attenuated approximately 160 ms after the onset of the second flash
      when it was preceded by a multisensory event. Source estimations further
      indicated that this attenuation occurred within low-level visual cortices.
      Multisensory interactions are ongoing in low-level visual cortices and affect
      incoming sensory processing. These data provide evidence that multisensory
      interactions are not restricted in time and can dramatically influence the
      treatment of subsequent stimuli, opening new lines of multisensory research.

PMID- 17215145
TI  - Functional neuroimaging of word priming in males with chronic schizophrenia.
AB  - Word-priming studies have suggested that the associative disturbance of
      schizophrenia may reflect aberrant spread of activation through the lexicon of
      the brain. To explore this, we examined lexical activation using a semantic word
      priming paradigm coupled with functional magnetic resonance imaging (fMRI). We
      also wanted to determine whether brain activation to this paradigm correlated
      with relevant clinical symptom measures. In addition to completing clinical
      symptom measures, twelve chronic patients and twelve demographically matched
      control subjects completed a lexical-decision semantic-priming paradigm developed
      as an event-related BOLD fMRI task. This paradigm consisted of words that
      differed in connectivity. Words with many connections between shared semantic
      associates are considered high in connectivity and produce the largest behavioral
      semantic priming effects in control subjects, while words with few connections
      between shared semantic associates are considered low in connectivity and produce
      a relatively smaller amount of semantic priming. In fMRI, a respective step-wise
      increase in activation from high connectivity to low connectivity to unrelated
      word pairs was expected for normal subjects. Controls showed the expected pattern
      of activation to word connectivity; however, patients showed a less robust
      pattern of activation to word connectivity. Furthermore, this aberrant response
      correlated with measures of Auditory Hallucinations, Distractive Speech,
      Illogicality, and Incoherence. The patients did not display left frontal and
      temporal activation as a function of the degree of word connectivity as seen in
      healthy controls. This may reflect a disease-related disturbance in functional
      connectivity of lexical activation, which in turn may be associated with clinical
      symptomatology.

PMID- 17215146
TI  - RNA targeted therapeutics for hematologic malignancies.
AB  - In a variety of experimental systems, antisense nucleic acids (ASNA) of various
      composition, including antisense oligodeoxynucleotides (ODN) and siRNA, have been
      shown to have the ability to variably perturb gene expression in a sequence
      specific manner. Pilot clinical studies from our group, and others, have
      demonstrated that gene silencing is a therapeutic strategy that is starting to
      make a real contribution to the treatment of various diseases. The development of
      this field, with specific reference to hematologic malignancies, is reviewed very
      briefly below.

PMID- 17215147
TI  - Regulation of TRP channels by N-linked glycosylation.
AB  - A subset of TRP channel proteins undergoes regulatory N-linked glycosylation. A
      glycosylation site in the first extracellular loop of TRPV5 is enzymatically
      cleaved by a secreted glucuronidase, indirectly regulating channel function.
      Members of the TRPC family share a similar site, although details about a
      regulatory role are lacking. A second conserved TRP channel glycosylation site is
      found immediately adjacent to the channel pore-forming loop; both TRPV1 and TRPV4
      -and perhaps other TRPV family members--are influenced by glycosylation at this
      site. N-linked glycosylation, and the dynamic regulation of this process,
      substantially impacts function and targeting of TRP channels.

PMID- 17215148
TI  - Finally--sleep science for the courtroom.

PMID- 17215149
TI  - Gene expression during oosporogenesis in heterothallic and homothallic
      Phytophthora.
AB  - A large-scale screen for genes induced during sexual development was performed in
      the heterothallic oomycete Phytophthora infestans, the potato blight agent. Of
      15,644 unigenes on an Affymetrix chip, 87 were induced >10-fold during mating,
      with 28 induced >100-fold. This was validated in independent matings using RNA
      blots and RT-PCR. Only 44 genes resembled sequences in GenBank. These encoded
      regulators such as protein kinases, protein phosphatases, and transcription
      factors, plus enzymes with metabolic, transport, or cell-cycle activities.
      Several genes were induced during both mating and asexual sporogenesis,
      suggesting crosstalk between those pathways. In the homothallic species P.
      phaseoli, 20% of the 87 genes were expressed at higher levels during conditions
      conducive to oosporogenesis than non-conducive conditions, while the rest were at
      similar levels. Many of the latter exhibited higher mRNA concentrations in P.
      phaseoli than in any non-mating culture of P. infestans, suggesting that part of
      the sexual pathway is active constitutively in homothallics.

PMID- 17215150
TI  - Canine leishmaniasis: a diagnostic and clinical challenge.

PMID- 17215151
TI  - Meticillin-resistant Staphylococcus aureus in animals: a review.
AB  - The objectives of this paper are to review published data on the prevalence and
      epidemiology of meticillin-resistant Staphylococcus aureus (MRSA) infection and
      colonization in animals and to provide suggestions for preventing and controlling
      the problem in veterinary practice. MRSA first emerged as a serious pathogen in
      human medicine during the late 1970s and has been increasingly reported in
      animals during the past 10 years. The prevalence of MRSA in human infections
      varies markedly between geographical areas, being as high as 60% in parts of the
      USA, 40% in southern Europe but <1% in northern Europe. Epidemiological evidence,
      including phenotypic and molecular typing data, suggests that MRSA isolates from
      dogs and cats are indistinguishable from human healthcare isolates, whereas
      strains of MRSA isolated from horses and associated personnel are different.
      There is evidence that transfer of MRSA strains can occur between animals and
      humans and vice versa. Guidelines for the control of MRSA in animals have been
      drawn up by individual institutions based on those available for human MRSA
      infection. Risk factors for MRSA infection in animals are currently under
      investigation and such data are essential for the preparation of specific
      guidelines for control of MRSA in veterinary practice.

PMID- 17215152
TI  - WITHDRAWN: The Pathobiological Mechanisms of Emphysema Models: What do They Have
      in Common?
AB  - The publisher regrets that this is an accidental duplication of an article that
      has already been published inPulm. Pharmacol. Ther., 16 (2003) 67-78,
      doi:10.1016/S1094-5539(02)00099-8. The duplicate article has therefore been
      withdrawn.

PMID- 17215153
TI  - WITHDRAWN: Short- and Long-term Reproducibility of Capsaicin Cough Challenge
      Testing.
AB  - The publisher regrets that this is an accidental duplication of an article that
      has already been published inPulm. Pharmacol. Ther., 16 (2003) 61-65,
      doi:10.1016/S1094-5539(02)00149-9. The duplicate article has therefore been
      withdrawn.

PMID- 17215154
TI  - WITHDRAWN: The Inhalers of the Future? A Review of Dry Powder Devices on the
      Market Today.
AB  - The publisher regrets that this is an accidental duplication of an article that
      has already been published inPulm. Pharmacol. Ther., 16 (2003) 79-95,
      doi:10.1016/S1094-5539(02)00147-5. The duplicate article has therefore been
      withdrawn.

PMID- 17215155
TI  - The role of vitellogenin during gestation of Girardinichthys viviparus and Ameca
      splendens; two goodeid fish with matrotrophic viviparity.
AB  - Goodeid fish have matrotrophic viviparity, and unlike lecitotrophic fish, yolk
      loss forces the female to provide the nutritional requirements for embryonic
      development. Vitellogenin (VTG) is the yolk precursor protein synthesized in the
      maternal liver, but there is only circumstantial evidence regarding VTG supply
      during the ontogenesis of bony fish with matrotrophic viviparity. Therefore, the
      goal of the present study was to identify and quantify VTG during gestation of
      the black fin goodeid Girardinichthys viviparus and the butterfly split-fin
      goodeid Ameca splendens. Females at different gonadic developmental stages were
      selected in order to evaluate VTG mRNA expression in the maternal liver using RT
      PCR; VTG quantification in maternal muscle and liver, as well as in the embryos,
      was done using ELISA, and immunohistochemical detection of VTG was done in the
      black fin goodeid. The results suggest that VTG supplies nutrients during
      embryonic development of both species, which have different life histories. It is
      possible that the transition from lecitotrophy to matrotrophic viviparity in bony
      fish with intraluminal gestation involved adaptive transition strategies that
      included changes in the relationship between oocytes and follicular cells, as
      well as a gradual loss of VTG synthesis during embryonic development.

PMID- 17215156
TI  - Molecular characterization and classification of a clip domain containing
      peptidase from the ectoparasite Lepeophtheirus salmonis (Copepoda, Crustacea).
AB  - Clip domain containing serine peptidases (CSPs) include one or more N-terminal
      clip domain(s) and a C-terminal serine peptidase domain that shares traits with
      both chymotrypsin and trypsin. CSPs are found in arthropods and are involved in
      embryonic patterning, immune responses and blood clotting. Among crustaceans only
      one CSP, which activates prophenoloxidase in crayfish, have previously been
      reported. We here present LsCSP1, the first CSP found in copepods. LsCSP1 is
      expressed in the subcuticular tissue and the transcription appears to be
      upregulated during development. In conjunction with previous studies of CSPs,
      this study suggests that LsCSP1 may play a role in the immune responses of L.
      salmonis. Phylogenetic and structural analyses indicate that the CSPs and
      catalytically inactive CSP homologs (CSPHs) constitute a monophyletic lineage.

PMID- 17215157
TI  - Study of goldfish (Carassius auratus) growth hormone structure-function
      relationship by domain swapping.
AB  - Using goldfish as a model, the structure-function relationship of goldfish growth
      hormone was studied using the strategy of homologous domain swapping. Chimeric
      mutants were constructed by exchanging homologous regions between goldfish growth
      hormone (gfGH II) and goldfish prolactin (gfPRL) with their cloned complementary
      DNAs. Six mutants, with their domain-swapped, were generated to have different
      combinations of three target regions, including the helix a, helix d and the
      large section in between these helices (possess the helices b, c and other random
      coiled regions). After expression in E. coli and refolding, these mutants were
      characterized by using competitive receptor binding assay (RRA) and growth
      hormone responding promoter activation assay. The different activity profiles of
      mutants in Spi 2.1 gene promoter assays from that in RRA shows that, for gfGH,
      receptor binding dose not confer receptor signal activations. When either helices
      a or d of gfGH was maintained with other helices replaced by their gfPRL
      counterparts, both receptor binding and hence gene activation activities are
      reduced. In mutants with helices b and c in gfGH maintained, containing the gfGH
      middle section, and helices a and d swapped with gfPRL, the had reduced RRA
      activities but the promoter activation activities retained. In conclusion, as in
      the case of human GH, the gfGH molecule possesses two functional sites: one of
      them is composed of discontinuous epitopes located on the target regions of this
      study and is for receptor binding; another site is located on the middle section
      of the molecule that helices a and d are not involved, and it is for activation
      of GH receptor and intracellular signals.

PMID- 17215159
TI  - Changes in the activity of acid glycosidases during posthatch development and
      regression after light reduction of Japanese quail testes and epididymides.
AB  - In this study specific activities of four acid glycosidases: beta-N
      acethylhexosaminidase (beta-HEX), beta-galactosidase (beta-GAL), alpha- and beta
      mannosidase (alpha- and beta-MAN) were investigated in Japanese quail testes and
      epididymides during posthatch development and regression after light reduction.
      The specific activity of testicular beta-HEX and beta-GAL increased steadily
      during posthatch development and assumed maximum values for testes weighing 200
      400 mg, when numerous spermatocytes appear in the testes of quail, and then
      decreased slowly. These enzymes showed much higher specific activity after 15
      days of light reduction, and decreased to the control level after 30 days.
      Activity of alpha- and beta-MAN remained rather constant during testicular
      development and involution. The epididymal activity of the acid glycosidases was
      very low in immature individuals, whereas in sexually mature birds it was found
      to increase several-fold. Short photoperiod resulted in a decreased activity of
      these enzymes after 30 days to the values found in immature birds. A marked
      increase in the activity of acid glycosidases in the epididymides of sexually
      mature animals and a decrease in this activity during epididymidal regression
      indicate that these enzymes take part in reproductive processes. It is concluded
      that the activities of beta-HEX, beta-GAL, alpha- and beta-MAN in the development
      and regression of Japanese quail testes and epididymides change similarly as in
      mammals.

PMID- 17215158
TI  - Tissue-specific modulation of glucocorticoid receptor expression in response to
      salinity acclimation in rainbow trout.
AB  - While studies clearly point to a role for cortisol signaling in seawater
      adaptation, very little is known about salinity impact on glucocorticoid receptor
      (GR) expression in fish. To this end, we investigated the temporal GR expression
      in the gill and liver of rainbow trout (Oncorhynchus mykiss) to salinity
      exposure. Trout were subjected to gradual salinity increases (11 ppt for 1 d, 17
      ppt for 2 d and 23 ppt for 2 d) over a five day period. Gill Na(+), K(+)-ATPase
      alpha-subunit mRNA showed a transient elevation with salinity exposure, while
      gill cystic fibrosis transmembrane conductance regulator mRNA was not
      significantly affected by salinity. Liver PEPCK transcript levels showed a
      transient increase at day 1, but not at day 3 or day 5 of salinity exposure,
      while the activity of this enzyme was significantly depressed at all time points.
      Liver glycogen content was also significantly reduced by salinity exposure
      compared to the freshwater group. Gill GR transcript levels were 3-fold greater
      upon salinity exposure and this level was maintained over the 5 day period, while
      gill GR protein content remained unchanged except for a significant drop at day 1
      of salinity exposure. Liver GR transcript levels showed no significant change
      with salinity exposure, while GR protein content was transiently elevated at day
      3, but not at day 1 or day 5 of salinity exposure. The tissue-specific GR
      transcript response in the gill leads us to hypothesize a role for osmosensory
      signal transduction pathway in the regulation of GR expression in fish.
      Collectively, salinity exposure modulates GR expression and glucocorticoid
      signaling in rainbow trout.

PMID- 17215160
TI  - Molecular cloning and sequence analysis of the cDNA encoding thyroid-stimulating
      hormone beta-subunit of common duck and mule duck pituitaries: in vitro
      regulation of steady-state TSHbeta mRNA level.
AB  - For better understanding of phylogenetic diversity and evolution of pituitary
      thyroid-stimulating hormone (TSH) in birds, we have cloned the cDNAs encoding TSH
      beta subunit (TSHbeta), by reverse transcription-polymerase chain reaction (RT
      PCR) and rapid amplification of cDNA ends (RACE) from two species of domestic
      ducks, common duck (Tsaiya duck and Pekin duck) (Anas platyrhynchos domesticus)
      and mule duck (hybrid of male muscovy duck Cairina moschata and female A.
      platyrhynchos domesticus). The nucleotide sequences of isolated TSHbeta cDNAs of
      the two species of ducks are identical, with each including 66 bp of 5'
      untranslated region (UTR), 402 bp of coding region, and 82 bp 3'-UTR followed by
      18 bp poly A tract. The deduced TSHbeta subunit of the ducks contains 134 amino
      acids consisting of a putative signal peptide of 19 amino acids and a putative
      mature protein of 115 amino acids. However, the TSHbetas of common duck and mule
      duck differ from the TSHbeta of muscovy duck in one amino acid at position 97 of
      the mature protein: isoleucine for common duck and mule duck, and valine for
      muscovy duck. Our findings thus demonstrate that inter-genus variation of TSHbeta
      exists in Family Anatidae, and that TSHbeta gene in the mule duck is
      preferentially transcribed from the maternal genome rather than from the paternal
      genome. TSHbeta mRNA expressions were investigated by culturing common duck
      pituitaries with various doses of hormones. Thyrotropin-releasing hormone (TRH)
      stimulated, while thyroid hormones, triiodothyronine (T(3)) and thyroxine (T(4)),
      inhibited the TSHbeta mRNA levels, in dose-related manners. The findings thus
      support that the mode of regulation of TSH gene expression in hypothalamo
      pituitary-thyroid axis in birds is similar to that in mammals. Cortisol and
      corticosterone decreased the steady-state TSHbeta mRNA levels at the pituitary
      level, in a dose-related manner, the first-time demonstration in vertebrates. The
      results may suggest that glucocorticoids exert suppressive action directly at
      pituitary level in modulation of steady-state TSHbeta mRNA level.

PMID- 17215161
TI  - [Are French results in assisted reproductive techniques so bad?].

PMID- 17215162
TI  - Visual performance after overnight orthokeratology.
AB  - PURPOSE: To investigate visual performance after overnight orthokeratology in
      terms of changes from baseline values, regression of the orthokeratology effect
      over time, and evaluation of the best-corrected vision after treatment. In
      particular, to evaluate any residual visual deficits over the duration of a day
      due to the abnormal corneal topography induced by orthokeratology treatment.
      METHOD: One eye of each of six subjects was fitted with custom designed BE
      orthokeratology lenses (Capricornia, Brisbane, Australia), with the fellow eye
      acting as a control. Unaided vision, subjective sphero-cylindrical refraction,
      high contrast high luminance visual acuity, low contrast high luminance visual
      acuity, high contrast low luminance visual acuity and letter contrast sensitivity
      were measured at baseline and after one night (Day 1) and eight nights (Day 8) of
      lens wear. Except for baseline, data were collected after overnight lens wear
      immediately after lens removal, and again 3, 6 and 9h after lens removal. At each
      time point throughout the day, the visual performance measures were evaluated
      with the initial refraction of the day (the 0h refraction) and also using the
      optimum subjective refraction at each measurement time. This method was used to
      evaluate the practical visual performance to be expected after orthokeratology
      treatment and the residual visual deficits arising from any induced corneal
      changes after correction of defocus. RESULTS: As expected, orthokeratology lens
      wear significantly changed unaided vision and refraction from baseline. However,
      it did not significantly affect visual acuity in different contrast conditions,
      or contrast sensitivity. The spherical component of refraction was the only
      parameter to exhibit regression over each day (p=0.021), with more stability
      demonstrated on Day 8 than Day 1 (p=0.012). There were no statistically
      significant changes of best-corrected acuity from baseline in the differing
      contrast and luminance conditions. CONCLUSION: Apart from the predicted
      improvements in unaided vision and reduction of the myopic refractive error,
      orthokeratology treatment was not found to significantly change any other aspects
      of visual acuity and contrast sensitivity. All visual performance measures
      exhibited stability over a 9-h period. Spherical refractive error changed
      significantly on Day 1 but became stable after a week of treatment. These results
      indicate that the corneal topography changes induced by orthokeratology do not
      induce changes in aberrations that are large enough to significantly diminish
      visual performance.

PMID- 17215163
TI  - Microbial phenotypic heterogeneity and antibiotic tolerance.
AB  - Phenotypic heterogeneity, defined as metastable variation in cellular parameters
      generated by epigenetic mechanisms, is crucial for the persistence of bacterial
      populations under fluctuating selective pressures. Diversity ensures that some
      individuals will survive a potentially lethal stress, such as an antibiotic, that
      would otherwise obliterate the entire population. The refractoriness of bacterial
      infections to antibiotic therapy has been ascribed to antibiotic-tolerant
      variants known as 'persisters'. The persisters are not drug-resistant mutants and
      it is unclear why they survive antibiotic pressure that kills their genetically
      identical siblings. Recent conceptual and technological advances are beginning to
      yield some surprising new insights into the mechanistic basis of this clinically
      important manifestation of phenotypic heterogeneity.

PMID- 17215165
TI  - Insulin resistance, physical fitness, body composition and leptin concentration
      in 7-8 year-old children.
AB  - The aim of this study was to investigate the association between insulin
      resistance and physical fitness, leptin concentration, body composition and
      family history for diabetes in non-selected young children. Physical fitness,
      fasting plasma glucose, insulin and leptin concentrations, anthropometric
      characteristics and medical history were available in two hundred and fifty-seven
      7-year-old Dutch children. Correlations with the homeostasis model assessment
      (HOMA) index for insulin resistance were studied. A multiple regression model was
      calculated for HOMA. The differences between children with or without a family
      history for diabetes were not significant. Boys scored higher on glucose
      concentration and aerobic fitness and lower on sum of skin folds and leptin
      concentration (p<.05). After adjustment for sum of skin folds, HOMA was
      significantly associated with leptin in both genders (boys r=.184 p=.031; girls
      r=.430 p=.000). The association between physical fitness and HOMA was mediated by
      sum of skin folds. The associations were stronger in girls than in boys. In the
      regression model (R(2)=.205) the leptin concentration was the only significant
      predictor for HOMA. The influence of family history for diabetes on insulin
      resistance is shown as a trend at this age. Our findings suggest that plasma
      leptin concentration is independently associated with the development of insulin
      resistance in a non-selected prepubertal population. The association of physical
      fitness with insulin resistance seems to be mediated by the sum of skin folds.

PMID- 17215167
TI  - Bacterial flora of the female genital tract: function and immune regulation.
AB  - The use of non-culture gene amplification techniques has improved our
      understanding of the composition of the vaginal bacterial ecosystem. In most
      healthy women in the reproductive period the predominant vaginal bacteria are one
      or more of the following species of Lactobacillus: L. crispatus, L. iners and L.
      gasseri. However, in other apparently healthy women lactobacilli may be deficient
      or absent, being replaced by other lactic-acid-producing bacteria: Atopobium,
      Megasphaera and/or Leptotrichia species. Infection and/or proliferation of
      pathogenic bacteria in the vagina is suppressed by lactic acid production,
      bacteria-generated antimicrobial products, and the local activities of the innate
      and cell-mediated immune systems. Vaginal epithelial cells produce a range of
      compounds with antimicrobial activities. These cells also possess membrane-bound
      Toll-like receptors that recognize pathogen-associated molecular patterns.
      Recognition leads to pro-inflammatory cytokine production and antigen-specific
      immunity. Local production of IgG and IgA antibodies can also be initiated in the
      endocervix and vagina in response to infection.

PMID- 17215164
TI  - Effects of rosiglitazone and high fat diet on lipase/esterase expression in
      adipose tissue.
AB  - A number of intracellular lipase/esterase have been reported in adipose tissue
      either by functional assays of activity or through proteomic analysis. In the
      current work, we have studied the relative expression level of 12 members of the
      lipase/esterase family that are found in white adipose tissue. We found that the
      relative mRNA levels of ATGL and HSL are the most abundant, being 2-3 fold
      greater than TGH or ADPN; whereas other intracellular neutral lipase/esterases
      were expressed at substantially lower levels. High fat feeding did not alter the
      mRNA expression levels of most lipase/esterases, but did reduce CGI-58 and
      WBSCR21. Likewise, rosiglitazone treatment did not alter the mRNA expression
      levels of most lipase/esterases, but did increase ATGL, TGH, CGI-58 and WBSCR21,
      while reducing ADPN. WAT from HSL-/- mice showed no compensatory increase in any
      lipase/esterases, rather mRNA levels of most lipase/esterases were reduced. In
      contrast, BAT from HSL-/- mice showed an increase in ATGL expression, as well as
      a decrease in ES-1, APEH and WBSCR21. Analysis of the immunoreactive protein
      levels of some of the lipases confirmed the results seen with mRNA. In
      conclusion, these data highlight the complexity of the regulation of the
      expression of intracellular neutral lipase/esterases involved in lipolysis.

PMID- 17215168
TI  - Structural and functional neuroimaging correlates of depression in temporal lobe
      epilepsy.
AB  - Depression is commonly experienced among persons with temporal lobe epilepsy
      (TLE). Although evidence exists implicating dysfunction of distributed neural
      structure and circuitry among depressed persons without epilepsy, little is known
      regarding the neural correlates of depression in TLE. We examined the
      relationship between self-reported depression severity and both structural MRI
      volumetry and [(18)F]fluorodeoxyglucose positron emission tomography (PET)
      measured resting metabolism of the amygdala and hippocampus of 18 patients with
      TLE. Significant positive relationships were noted between right and left
      amygdala volumes and depression. No other significant relationships were observed
      between amygdala PET measures, hippocampal volumes, or hippocampal PET measures
      and degree of depressive symptomatology. These findings indicate that both right
      and left amygdala volumes are associated with depression severity among persons
      with TLE. Future studies examining the potential role of extended neural regions
      may clarify the observed structural relationship between depressive symptoms and
      the amygdala.

PMID- 17215169
TI  - Medication use profiles in patients with psychogenic nonepileptic seizures.
AB  - Patients with psychogenic nonepileptic seizures (PNES) and those with epilepsy
      may have very different medication use profiles. In this study, the authors set
      out to document and statistically compare medication use by these two
      populations. They found significant differences in the duration of antiepileptic
      medication use (shorter in those with psychogenic nonepileptic seizures, or PNES)
      and number of medications used (more in persons with PNES) and a tendency by
      patients with PNES to use narcotics and benzodiazepines. These results are
      discussed in the light of the pertinent literature.

PMID- 17215170
TI  - Temporal changes in gene expression in rainbow trout exposed to ethynyl
      estradiol.
AB  - We examined changes in the genomic response during continuous exposure to the
      xenoestrogen ethynyl estradiol. Isogenic rainbow trout Oncorhynchus mykiss were
      exposed to nominal concentrations of 100 ng/L ethynyl estradiol (EE2) for a
      period of 3 weeks. At fixed time points within the exposure, fish were
      euthanized, livers harvested and RNA extracted. Fluorescently labeled cDNA were
      generated and hybridized against a commercially available Salmonid array (GRASP
      project, University of Victoria, Canada) spotted with 16,000 cDNAs. The slides
      were scanned to measure abundance of a given transcript in each sample relative
      to controls. Data were analyzed via Genespring (Silicon Genetics) to identify a
      list of up and down regulated genes, and to determine gene clustering patterns
      that can be used as "expression signatures". Gene ontology was determined using
      the annotation available from the GRASP website. Our analysis indicates each
      exposure time period generated specific gene expression profiles. Changes in gene
      expression were best understood by grouping genes by their gene expression
      profiles rather than examining fold change at a particular time point. Many of
      the genes commonly used as biomarkers of exposure to xenoestrogens were not
      induced initially and did not have gene expression profiles typical of the
      majority of genes with altered expression.

PMID- 17215171
TI  - Direct and indirect inferences on parasite mating and gene transmission patterns.
      Pangamy in the cattle tick Rhipicephalus (Boophilus) microplus.
AB  - Mating system plays a determinant role in the maintenance and distribution of
      genetic variation. Difficulties in applying standard methods of indirect
      inferences onto parasitic life-cycles partly explain the current lack of
      knowledge on parasite mating systems. The present study develops a combination of
      direct and indirect inference methods circumventing such difficulties, and
      illustrates in particular how such a combination modifies our understanding of
      the biology of the southern cattle tick, Rhipicephalus microplus. To directly
      assess how females and males pair in natural populations, we sampled 225 mating
      pairs, genotyped them at six microsatellite loci, and analysed the correlation
      between mating status and genetic relatedness. This analysis revealed pangamy,
      i.e. a random association of male and female genotypes. In addition, indirect
      methods inferred that sib-groups of ticks exploit distinct individual-cows, and
      hence that ticks probably move among cows during their parasitic lifetime.
      Altogether, these results negate the expectation of a high frequency of sib
      mating, and show the coexistence of genetically diverging stocks within tick
      cohorts and populations. These results have several consequences for our
      understanding of R. microplus. For instance, while existing models of pesticide
      resistance management look perfectly applicable to this species, the
      epidemiological models of the micropathogens it vectors needs revision. More
      largely, the methods developed here would help clarify the evolutionary patterns
      of any dioceous parasite.

PMID- 17215172
TI  - Biological evaluation of an apatite-mullite glass-ceramic produced via selective
      laser sintering.
AB  - The biological performance of a porous apatite-mullite glass-ceramic,
      manufactured via a selective laser sintering (SLS) method, was evaluated to
      determine its potential as a bone replacement material. Direct contact and
      extract assays were used to assess the cytotoxicity of the material. A pilot
      animal study, implanting the material into rabbit tibiae for 4 weeks, was also
      carried out to assess in vivo bioactivity. The material produced by SLS did not
      show any acute cytotoxic effects by either contact or extract methods. There was
      no evidence of an apatite layer forming on the surface of the material when
      soaked in SBF for 30 days, suggesting that the material was unlikely to exhibit
      bioactive behaviour in vivo. It is hypothesized that the material was unable to
      form an apatite layer in SBF due to the fact that this glass-ceramic was highly
      crystalline and the fluorapatite crystal phase was relatively stable in SBF, as
      were the two aluminosilicate crystal phases. There was thus no release of calcium
      and phosphorus and no formation of silanol groups to trigger apatite deposition
      from solution within the test time period. Following implantation in rabbit
      tibiae for 4 weeks, bone was seen to have grown into the porous structure of the
      laser-sintered parts, and appeared to be very close to, or directly contacting,
      the material surface. This result may reflect the local environment in vivo
      compared to that artificially found with the in vitro SBF test and, furthermore,
      confirms previous in vivo data on these glass-ceramics.

PMID- 17215174
TI  - The role of nutrition in the prevention of coronary heart disease in women of the
      developed world.
AB  - Cardiovascular disease claims more than 500,000 women per year, making this
      disease the number one killer of women. Coronary heart disease in developed
      countries can be used as a representative classification when discussing
      cardiovascular disease management. Within the last 10 years research has
      illuminated the contributing risk factors and disease progression as they
      uniquely relate to women. Yet, current approaches to the prevention of primary
      risk factors in the development of cardiovascular disease fail to reach the
      potential described in scientific literature. Traditional prescriptions relied on
      hormone therapy or pharmacologic intervention to manage coronary heart diseases
      ignoring the non-hormonal aspects of cardiovascular health. Recent trends have
      begun to emphasize diet as a tool for the prevention of heart disease in women.
      This review attempts to highlight nutrition as a prescription that can be
      utilized to reduce the significant risk factors that women, who live in developed
      nations, face throughout their lifetime.

PMID- 17215175
TI  - Adiponectin represents an independent risk factor for hypertension in middle aged
      Korean women.
AB  - Adiponectin, which is secreted specifically by adipose tissue, has been shown to
      act as an anti-atherosclerotic protein. Several studies have shown that
      adiponectin levels are lower in individuals with obesity, diabetes and
      cardiovascular disease. The present study investigated relationships between
      serum adiponectin levels and body mass index (BMI), waist-to-hip ratio (WHR),
      blood pressure (BP) and lipid profiles in 300 middle-aged Korean women (mean age
      50.6 +/- 6.2; BMI 25.78 +/- 3.68 kg/m(2)). The serum adiponectin level was
      positively associated with high density lipoprotein (HDL)-cholesterol (r = 0.29)
      and negatively associated with BMI, WHR, percent body fat, triglyceride (TG),
      systolic BP, and diastolic BP. Multivariate logistic regression analysis revealed
      that increasing concentrations of adiponectin were associated with lower risk of
      hypertension. In overall odds ratios (95% CIs) for hypertension, those in the
      second, third, and fourth (versus the first) quartile of adiponectin after
      adjustment for age were 0.59 (0.297-1.185), 0.47 (0.236 - 0.938), and 0.32 (0.16 
      0.648), respectively. Regardless of BMI, WHR and percent body fat, higher
      adiponectin was independently associated with a lower risk of hypertension. These
      findings suggest that the serum adiponectin level is decreased with atherogenic
      lipid phenotype including hypertriglyceridemia and low HDL-cholesterol.
      Furthermore, low serum adiponectin concentration may be an independent risk
      factor for hypertension in middle-aged Korean women.

PMID- 17215176
TI  - Supplementation of a high-carbohydrate breakfast with barley beta-glucan improves
      postprandial glycaemic response for meals but not beverages.
AB  - There is growing support for the protective role of soluble fibre in type II
      diabetes. Soluble fibre beta-glucan found in cereal products including oats and
      barley may be the active component. There is evidence of postprandial blunting of
      blood glucose and insulin responses to dietary carbohydrates when oat soluble
      fibre is supplemented into the diet but few trials have been carried out using
      natural barley or enriched barley beta-glucan products. The aim of this trial was
      to investigate the postprandial effect of a highly enriched barley beta -glucan
      product on blood glucose, insulin and lipids when given with a high-CHO food and
      a high-CHO drink. 18 lean, healthy men completed a 4 treatment intervention trial
      comprising (i) high-CHO(food control), (ii) high-CHO(food+fibre), (iii) high
      CHO(drink control), (iv) high-CHO(drink+fibre) where a 10g dose of barley beta
      glucan fibre supplement (Cerogen) containing 6.31g beta-glucan was added to food
      and drink controls. There was an increase of glucose and insulin following all 4
      treatments. Addition of the beta -glucan supplement significantly blunted the
      glycaemic and insulinaemic responses on the food (p<0.05) but not drink (p>0.05)
      treatments when compared to controls. The high-CHO breakfasts decreased total,
      LDL- and HDL-cholesterol from baseline to 60 mins postprandially but there were
      no differential effects of beta-glucan treatment on circulating lipids. We
      conclude that a high dose barley beta-glucan supplement can improve glucose
      control when added to a high-CHO starchy food, probably due to increased gastro
      intestinal viscosity, but not when added to a high-CHO beverage where rapid
      absorption combined with decreased beta-glucan concentration and viscosity may
      obviate this mechanism.

PMID- 17215177
TI  - Reduction of adipose tissue and body weight: effect of water soluble calcium
      hydroxycitrate in Garcinia atroviridis on the short term treatment of obese women
      in Thailand.
AB  - Fifty obese women with a body mass index (BMI) over 25 kg/m(2) were randomly
      allocated into two groups, 25 in each. Group 1, with a mean (+/-SEM) age of
      40.0+/-2 years, received water soluble calcium hydroxycitrate (HCA) as Garcinia
      atroviridis. Group 2, with a mean age of 35.6+/-1.8 years, received placebo. All
      subjects were recommended a similar diet with 1000 Kcal/day. The trial lasted for
      2 months. At baseline the means BMI of Group 1 and Group 2 were 27.5+/-0.2
      kg/m(2) and 26.7+/-0.5 kg/m(2), respectively. Group 1 lost significantly more
      weight (2.8 vs. 1.4 kg, p<0.05) and at a greater rate than Group 2 throughout the
      study. The decrease in their body weight was due to a loss of fat storage as
      evidenced by a significant decrease in the triceps skin fold thickness. On a
      short-term basis, HCA in Garcinia atroviridis was an effective for weight
      management.

PMID- 17215178
TI  - Anti-cancer activities of pure curry feeding in cancer cell-transplanted mouse.
AB  - To confirm the cytotoxic effect of instant curry containing combined spices on
      cancer cells in vivo, cancer was induced by transplanting cancer cells to mice,
      and the development of cancer upon feeding pure curry were examined. The
      concentration of lipid peroxide in the groups transplanted with cancer cells
      which were fed with normal feed was 19.6 nM, and it was increased as the amount
      of pure curry was increased. The concentration of cytochrome P-450 was decreased
      in the group transplanted with cancer cells which were fed with pure curry and
      the group without the transplant which were fed with pure curry when compared
      with the groups which were fed with normal feed. The activity of cytochrome P-450
      was decreased as the concentration of cytochrome P-450 was decreased in the
      groups transplanted with cancer cells. However, it was increased in the groups
      without cancer cell transplant when over 2% of pure curry was fed. The amount of
      glutathione was increased in the groups transplanted with cancer cells when over
      2% of pure curry was fed. The activities of glutathione peroxidase and
      glutathione S-transferase were decreased in the groups transplanted with cancer
      cells which were fed with over 1% of pure curry, and were restored to the level
      of the group without cancer cell transplant which were fed with normal feed. The
      superoxide dismutase activity in the groups transplanted with cancer cells was
      restored to the level of the group without cancer cell transplant which was fed
      with normal feed when over 1% of pure curry was fed.

PMID- 17215179
TI  - Effects of phytosterols in diacylglycerol as part of diet therapy on
      hyperlipidemia in children.
AB  - BACKGROUND: The incidence of hyperlipidemia in children is increasing in Japan,
      but drug therapy for such children is limited. The ingestion of 4% phytosterols
      containing diacylglycerol (PS/DAG) decreases serum total cholesterol and low
      density lipoprotein cholesterol (LDL-C) concentrations in adults. In the present
      study, we examined the effect of PS/DAG as part of a diet therapy in pediatric
      patients with hyperlipidemia. METHODS: Pediatric patients with hyperlipidemia
      with > or =5.18mmol (200 mg/dL) serum total cholesterol and/or >or =1.70mmol (150
      mg/dL) triglycerides (N=22) ingested bread containing PS/DAG (total daily intake,
      10g) for 6 months. Blood chemistry was examined prior to and 2, 4, 6 months after
      the initiation of ingestion, and 4 months after the ingestion period. RESULTS: No
      significant differences in energy intake or cholesterol intake during the study
      period were found. After 4 months of ingestion of PS/DAG, LDL-C, lipoprotein(a) [
      Lp(a)], free fatty acids and total ketone bodies decreased significantly. In
      seven patients with familial hypercholesterolemia, total cholesterol and remnant
      like lipoprotein particles (RLP)-cholesterol also significantly decreased in
      addition to LDL-C and Lp(a). CONCLUSIONS: PS/DAG improves serum lipid metabolism
      in pediatric patients with hyperlipidemia for whom drug therapy is limited,
      suggesting that PS/DAG may reduce the risk of developing various diseases induced
      by hyperlipidemia.

PMID- 17215180
TI  - Anthropometric indices and life style practices of the indigenous Orang Asli
      adults in Lembah Belum, Grik of Peninsular Malaysia.
AB  - A nutritional status survey of Orang Asli (Aboriginal) adults in Lembah Belum,
      Grik, has been conducted involving a total of 138 subjects. Jahai (58.7%) was the
      main ethnic group as compared to that of Temiar (41.3%). Based on the Body Mass
      Index (BMI) characteristics, the majority (63.2%) of the respondents were normal,
      26.7% underweight and 10.1% were either overweight or obese. However, by using
      two different indices of waist circumference and waist-to-hip ratio, 1.6% and
      10.8% of the total respondents revealed abdominal obesity, respectively.
      Measurement of mid upper arm muscle circumference (MUAMC) indicated that about
      40% showed nutritional insufficiency whereas 0.8% showed over-nutrition. Body fat
      classification revealed that 53.4% of the respondents were thin, 45.8% at normal
      level and only 0.8% were obese. Student's t-test revealed a significant
      difference in anthropometric indices of body weight, height, MUAMC, triceps, sub
      scapular, supra-iliac and body fat according to gender. Meanwhile, analysis of
      variance (ANOVA) showed significant differences in body weight, waist
      circumference, WHR and body fat according to different age categories. It was
      also found that those who smoked had lower BMI compared with non-smokers. Alcohol
      consumption was associated with higher BMI and WHR among the respondents.
      Pearson's correlation test between anthropometric measurements and socio-economic
      and demographic factors showed that ethnic group was the strongest variable.

PMID- 17215181
TI  - Change in diet and body mass index in Taiwanese women with length of residence in
      Australia.
AB  - The purpose of this cross-sectional study was to examine and compare
      anthropometric measurements and dietary intake of Taiwanese Chinese females
      living in Taiwan and Australia, including any effect of length of Australian
      residence. Height, weight, waist and hip circumference and percent total body fat
      were measured and dietary intake estimated using a 7-day record. Participants
      were Taiwanese females without systemic disease (100 from Sydney metropolitan
      area, Australia, 97 from Ping-Tung County, Taiwan). Subjects in Australia had
      similar body mass index (weight-kg/height-m(2)) and percent total body fat but
      higher waist and hip circumference than those in Taiwan (22.9+/-3.0 vs. 22.8+/
      3.1 kg/m(2), p >0.05; 31.4+/-5.8 vs. 31.0+/-6.2 %, p >0.05; 76.2+/-7.5 vs. 72.1+/
      7.3 cm, p =0.0001; 97.3+/-6.2 vs. 93.3+/-6.2 cm, p =0.0001, respectively),
      significance unaffected by age adjustment. Total energy intake was higher in
      Australia (2367+/-574 vs. 1878+/-575 Kcal) as was the caloric adjusted intake of
      carbohydrate and saturated fat, measured as grams (342.8+/-91.5 vs. 264.9+/-91.0
      g; 30.7+/-9.1 vs. 23.0+/-9.1 g) or as percentage of caloric adjusted intake
      (57.3+/-1.4 vs. 55.6+/-2.3 %; 12.1+/-0.7 vs. 11.2+/-1.1 %), all p<0.001,
      respectively. There was a trend for anthropometric measures to increase in
      subjects who had lived in Australia greater than 5 years, and they also have 14
      times the odds of having a waist circumference greater than 80 cm compared to
      those living in Australia less than 5 years (95% CI, 1.84, 112.0). The increase
      in waist circumference and higher energy and saturated fat intake associated with
      length of residence in Australia for Taiwanese females suggests an increased risk
      of cardiovascular disease and diabetes.

PMID- 17215182
TI  - Can bioelectric impedance monitors be used to accurately estimate body fat in
      Chinese adults?
AB  - Many laboratory-based methods exist to estimate body fat, yet few can be rapidly
      and easily applied to field studies. Bioelectric impedance analysis (BIA) has
      developed to include portable foot-to-foot systems that can estimate body fat
      during field studies, but it is unclear if the data they provide are comparable
      to anthropometric methods traditionally used in large epidemiological fieldwork.
      This study analysed the reliability and validity of three BIA devices (low,
      medium, and high cost), from duplicate measures of mass and percentage body fat
      (%BF) from 20 young Chinese. Comparisons were made to reference values of %BF
      derived from 38 duplicated anthropometric measurements and the mean of at least 7
      regression equations. All three BIA devices were reliable, with intraclass
      correlation coefficients never below 0.999, whilst both technical errors of
      measurement and coefficients of variation (expressed as percentages) were below
      1%. Validity analysis revealed all three devices significantly overestimated %BF
      using the standard measurement setting (no correction for athletic status)
      compared to the reference method: UM-022 (+3.2%, p <0.01), BF-350 (+2.6%, p
      <0.01), and TBF-410 (+2.1%, p <0.01). When %BF was corrected for athletic status,
      neither the BF-350 (+0.3%, p =0.72), nor the TBF-410 (-0.2%, p =0.86) produced a
      %BF that differed significantly from the reference method. It was concluded that
      these three BIA devices were reliable and could be recommended as valid field
      measures of mass and %BF in this sample population provided the device allows a
      correction for athletic status.

PMID- 17215183
TI  - Gender and socio-economic differences in BMI of secondary high school students in
      Ho Chi Minh city.
AB  - OBJECTIVE: To assess the nutritional status of adolescents in Ho Chi Minh City,
      and in particular determine the prevalence of overweight and obesity in
      adolescents across different sub groups, based on gender, household economic
      status and geographic location. DESIGN: A cross-sectional survey based on a two
      stage cluster sampling design. SETTING: Secondary high schools in Ho Chi Minh
      City. SUBJECTS: There were 1504 adolescents involved in the study, of which 50%
      were girls and the mean age of participants was 13.1 years. RESULTS: Overall,
      4.9% of the students were overweight and 0.6% were obese, while 13.1% of the
      students were underweight. The prevalence of underweight was significantly higher
      in boys than girls (p=0.001) and overweight and obesity were also higher in boys
      although these differences were not statistically significant (p=0.074). There
      was a much higher prevalence of overweight and obesity in students from schools
      in wealthy urban districts (8.2% and 0.6%, respectively) in comparison to
      students from schools in rural or semi-rural districts (1.6% and 0.2%,
      respectively) and these differences were statistically significant (p<0.001).
      CONCLUSIONS: A transition in nutritional status is underway in this population of
      adolescents where overweight and obesity are emerging as a public health problem,
      but underweight remains a significant problem.

PMID- 17215184
TI  - Intervention with traditional food as a major source of energy, protein, iron,
      vitamin C and vitamin A for rural Dalit mothers and young children in Andhra
      Pradesh, South India.
AB  - Intakes of energy, protein, iron and vitamin A in India are usually reported as
      inadequate. Recognizing that traditional food systems are sustainable, high in
      species variety, and have rich nutrient sources, we compared dietary intakes and
      nutrient sources of Dalit mothers and their children living in villages with and
      without an intervention based on improved access to the traditional Dalit food
      system. 24-hour recalls were conducted with Dalit mothers and their children aged
      6-39 months during summer and rainy seasons in 2003. We found that mothers from
      intervention villages had significantly higher intakes of energy (mean +/- SD:
      12,197 +/- 3,515 kJ vs. 11,172 +/- 3,352 kJ; p =0.02) and protein (77.5 +/- 25.1
      g vs. 71.1 +/- 25.2 g; p =0.05) in summer, and higher intakes of energy (11,168
      +/- 3,335 kJ vs. 10,168 +/- 3,730 kJ; p = 0.04), protein (68.9 +/- 22.6 g vs.
      60.4 +/- 23.8 g; p <0.01) and iron (15.8 +/- 6.6 mg vs. 13.7 +/- 9.1 mg; p <0.01)
      during rainy season. There were no differences in children's intakes between
      intervention and control villages. In mothers, sorghum contributed 29% of energy,
      33% of protein and 53% of iron, and green leafy vegetables contributed 21% of
      vitamin C and 38% of vitamin A. Our results indicate that traditional food such
      as sorghum, pulses and green leafy vegetables are major sources of energy,
      protein, iron, vitamin C and vitamin A, and that mothers from villages with the
      traditional food intervention had higher intakes of energy, protein and iron.

PMID- 17215185
TI  - Impact of vitamin A supplementation on health status and absenteeism of school
      children in Sri Lanka.
AB  - The objective of this study was to determine the impact of Vitamin A
      supplementation on health status and absenteeism of school children. A randomized
      double blind placebo controlled trial over a period of 13 months was conducted in
      a rural area of Sri Lanka involving 613 school children attending Grades 1-5
      (aged 5 to 13 years). Children were assigned to either 200,000 IU of Vitamin A
      (n=297) or placebo (n=316) once every 4 months. Socio-demographic data were
      obtained at baseline, and anthropometry and haemoglobin concentrations were
      assessed at baseline and post intervention. Serum vitamin A concentrations were
      assayed by HPLC in a subgroup of children (n=193) before administration of each
      dose. School absenteeism was recorded. The two groups of children were similar at
      baseline in all variables. The subgroup of children was comparable to the main
      study population. The prevalence of vitamin A deficiency (< 20 microg/dL) in the
      subgroup of children was 8.2%. Changes in anthropometric indices and haemoglobin
      concentrations were similar in the two groups. The major causes for absenteeism
      were non-health causes and supplemented children lost a fewer number of school
      days due to illness than placebo children (p=0.053). Vitamin A concentrations
      improved with each dose and the improvement was greater with better compliance.
      Vitamin A supplementation with 200,000 IU every 4 months over 13 months improved
      vitamin A status and school attendance but not anthropometric status of these
      children.

PMID- 17215186
TI  - Oral vitamin B12 supplementation reduces plasma total homocysteine concentration
      in women in India.
AB  - People in India have a high prevalence of low vitamin B12 status and high plasma
      total homocysteine (tHcy) concentrations. In a proof of principle trial, we
      studied the effect of oral vitamin B12 (500 microg) and/or 100 g cooked green
      leafy vegetables (GLV) every alternate day in a 2x2 factorial design over a 6
      week period. Forty-two non-pregnant vegetarian women (age 20-50 years) were
      randomly allocated to four study groups. Clinical measurements were made at the
      beginning and at the end of the study, and blood samples were collected before,
      and 2 and 6 weeks after commencement of intervention. Forty women completed the
      trial. Twenty-six women had low vitamin B12 status (<150 pmol/L) and 24 had
      hyperhomocysteinemia (>15 micromol/L). GLV supplementation did not alter plasma
      folate or tHcy. Vitamin B12 supplementation increased plasma vitamin B12
      concentration (125 to 215 pmol/L, p <0.05) and reduced tHcy concentration (18.0
      to 13.0 micromol/L, p <0.05) within first 2 weeks, both of which remained stable
      for the next 4 weeks. Plasma vitamin B12 and tHcy concentrations did not change
      in those who did not receive vitamin B12, and there was no change in plasma
      folate concentration in any of the groups. Blood haemoglobin concentration
      increased marginally within first two weeks in those women who received vitamin
      B12 (by 3 g/L, p <0.05) and the number of women with macrocytosis decreased from
      2 to zero. There was no change in vibration sensory threshold during the period
      of the study. High-dose per oral vitamin B12 supplementation significantly
      reduced plasma tHcy within 2 weeks but did not achieve normal plasma tHcy
      concentration even after 6 weeks. People in India have a high prevalence of low
      vitamin B12 status and high plasma total homocysteine (tHcy) concentrations.

PMID- 17215187
TI  - Metabolic fate of intravenously administered N-acetylneuraminic acid-6-14C in
      newborn piglets.
AB  - BACKGROUND: Sialic acid (N-acetylneuraminic acid), a component of gangliosides
      and sialylglycoproteins, may be a conditional nutrient in early life because
      endogenous synthesis is limited. The aim of this study was to investigate the
      metabolic fate of intravenously administrated N-acetylneuraminic acid-6-14C
      (sialic acid) in piglets. METHOD: Three-day-old male domestic piglets (Sus
      scrofa) were injected via the jugular vein with 5 microCi (11-12 x 10(6) cpm) of
      N-acetylneuraminic acid-6-14C (specific activity of 55 mCi/mmol). Blood samples
      were collected at regular intervals over the next 120 min. The organs were then
      removed and the urine collected for determination of residual radioactivity.
      RESULTS: Within 2 min of injection, 80% of the activity was removed from the
      blood and by 120 min the remaining activity approached 8%. At 120 min, the brain
      contained significantly more radioactivity (cpm/g tissue) than the liver,
      pancreas, heart and spleen, but less than the kidneys. Within the brain, the
      percentage of total injected activity was highest in the cerebrum (0.175 +/
      0.008) followed by the cerebellum (0.0295 +/-0.006, p=0.00006) and the thalamus
      (0.029 +/- 0.006, p =0.00003). CONCLUSIONS: An exogenous source of sialic acid is
      capable of crossing the blood-brain barrier and being taken up into various
      tissues. The findings suggest that dietary sources of sialic acid may contribute
      to early brain development in newborn mammals.

PMID- 17215188
TI  - Effects of wheat flour fortified with different iron fortificants on iron status
      and anemia prevalence in iron deficient anemic students in Northern China.
AB  - OBJECTIVES: To compare the effects of wheat flours fortified with NaFeEDTA, FeSO4
      and elemental iron (electrolytic iron), in improving iron status in anemic
      students. METHODS: Four hundreds anemic students (11 to 18 years old) were
      divided into four groups and given wheat flour fortified with different iron
      fortificants at different concentrations: control group (no added iron); NaFeEDTA
      group (20 mg Fe/kg); FeSO4 group (30 mg Fe/kg); and elemental iron group (60 mg
      Fe/kg). The trial lasted for 6 months and the following parameters were examined
      every 2 months: whole blood hemoglobin, free erythrocyte protoporphyrin, serum
      ferritin, serum iron, total iron binding capacity and transferrin receptor.
      RESULTS: The flour consumption in the 4 groups was 300-400 g/person/day,
      accounted for 70% of total cereal consumption in the diets. There were no
      significant differences in flour consumption among the 4 groups. Blood hemoglobin
      level increased in all the 3 intervened groups, but the increment in the NaFeEDTA
      group was significantly higher and earlier than the other 2 groups; and only 1%
      of the subjected remained anemic at the end of the trial in the NaFeEDTA group,
      while 40% and 60% of the subjects in the FeSO4 and electrolytic iron group
      remained anemic, respectively. The order of improvements in free erythrocyte
      protoporphyrin, serum ferritin and transferring receptor levels were: NaFeEDTA >
      FeSO4 > electrolytic iron. No significant changes were found in the control group
      on all the tested parameters during the trial. CONCLUSIONS: The results indicated
      that even NaFeEDTA was added at a lower level, it has better effects than FeSO4
      and elemental iron on controlling iron deficiency anemia and improving iron
      status in anemic children; while elemental iron was the least effective.

PMID- 17215189
TI  - Salt usage behaviors are related to urinary sodium excretion in normotensive
      Korean adults.
AB  - High sodium intake is considered to be the major risk factor for hypertension but
      studies about sodium intake on prevention and management of hypertension is
      limited due to the difficulties in assessment of sodium intake. Dietary sodium
      comes not only from naturally occurring sodium in foods but also from the added
      sodium during processing, cooking and at the table. Present study was conducted
      to identify salt usage behavior questions related to urinary sodium excretion
      among normotensive adult Koreans. The test version of the salt usage
      questionnaire included six items of salt usage behaviors and nine items of high
      salt containing foods. A survey was conducted in 189 adults over 18 years of age
      in three age groups in both genders. Each participant answered the questionnaire
      and collected one 24-hour urine and urine samples were analyzed for sodium
      contents. Correlation analyses between scores of the questions and sodium
      excretion in 24-hour urine were performed to identify question items related to
      sodium excretion. Among fifteen questions, scores of three questions on salt
      usage behaviors were significantly correlated to urinary sodium excretion
      (r=0.17~0.19; p <0.05) and the sum of scores of the three questions showed higher
      correlation coefficients. (r=0.26, p <0.001) The salt usage behavior questions
      developed in this study would be useful in predicting sodium intake and in
      studying the relationship between sodium intake and health among Korean adults.

PMID- 17215190
TI  - Establishment of an isoflavone database for usual Korean foods and evaluation of
      isoflavone intake among Korean children.
AB  - Asian populations including Koreans are assumed to have a higher isoflavone
      intake due to the higher consumption of soybean. However, it is difficult to
      estimate isoflavone intake because there is no isoflavone database in Korea. In
      this study, an isoflavone database was established with systematic review.
      Literature with analytical values of Korean soybeans and its products were
      collected and evaluated to establish an isoflavone database. A total of 142 food
      items containing isoflavones were selected among 2,932 food items in the Korean
      Nutrient Database. Among these, only 25 food items were evaluated with analytical
      values and the remaining 98 items were replaced with adaptations or calculations
      from similar items. Dietary intake of isoflavones was assessed for 426 boys and
      365 girls aged 8 to 11 years with 3-day food records. The daily mean isoflavone
      intake was 8.3 mg among boys and 7.2 mg among girls. More than 70% of subjects
      had a daily isoflavone intake below 10 mg. The most contributory food item to the
      isoflavone intake among adolescents was tofu in quantity and soybean sauce in
      frequency. This database could be used to estimate isoflavone intakes from
      dietary data among various populations and to evaluate the relationships between
      isoflavone intake and chronic disease.

PMID- 17215191
TI  - Content of a novel online collection of traditional east African food habits
      (1930s-1960s): data collected by the Max-Planck-Nutrition Research Unit, Bumbuli,
      Tanzania.
AB  - BACKGROUND: Knowledge of traditional African foods and food habits has been, and
      continues to be, systematically extirpated. With the primary intent of collating
      data for our online collection documenting traditional African foods and food
      habits (available at: www.healthyeatingclub.com/Africa/), we reviewed the
      Oltersdorf Collection, 75 observational investigations conducted throughout East
      Africa (i.e. Tanzania, Kenya, and Uganda) between the 1930s and 1960s as compiled
      by the Max Planck Nutrition Research Unit, formerly located in Bumbuli, Tanzania.
      METHODS: Data were categorized as follows: (1) food availability, (2) chemical
      composition, (3) staple foods (i.e. native crops, cereals, legumes, roots and
      tubers, vegetables, fruits, spices, oils and fats, beverages, and animal foods),
      (4) food preparation and culture, and (5) nutrient intake and health status
      indicators. RESULTS: Many of the traditional foods identified, including millet,
      sorghum, various legumes, root and tubers, green leafy vegetables, plant oils and
      wild meats have known health benefits. Food preparatory practices during this
      period, including boiling and occasional roasting are superior to current
      practices which favor frying and deep-frying. Overall, our review and data
      extraction provide reason to believe that a diversified diet was possible for the
      people of East Africa during this period (1930s-1960s). CONCLUSIONS: There is a
      wealth of knowledge pertaining to traditional East African foods and food habits
      within the Oltersdorf Collection. These data are currently available via our
      online collection. Future efforts should contribute to collating and honing
      knowledge of traditional foods and food habits within this region, and indeed
      throughout the rest of Africa. Preserving and disseminating this knowledge may be
      crucial for abating projected trends for non-communicable diseases and
      malnutrition in Africa and abroad.

PMID- 17215192
TI  - Sub clinical vitamin A deficiency and anemia among Vietnamese children less than
      five years of age.
AB  - The objective of the study was to assess the prevalence of sub clinical vitamin A
      deficiency and anemia in Vietnamese children. For this, a cross-sectional survey
      was conducted in 40 villages (clusters) of four ecological regions in Vietnam
      during Apr-May 2001. In total 1657 children less than 5 years old were included
      by a cluster random sampling method. The prevalence of sub clinical vitamin A
      deficiency (serum retinol <0.70 mumol/l) was 12.0% and the prevalence of anemia
      (hemoglobin <110g/l) was 28.4 %. 35.1%. In the children under 6 months the
      prevalence of sub clinical vitamin A deficiency was 35.1 % whereas the prevalence
      of anemia in this group was as high as 61.7%. The prevalence of children with
      both sub clinical vitamin A deficiency and anemia was 6.1%. Sub clinical vitamin
      A deficiency and anemia prevalence differed significantly across the regions,
      with highest prevalence in the Northern Mountainous areas for vitamin A
      deficiency and in the Northern Mountainous area and Mekong River Delta for
      anemia. It is concluded that sub clinical vitamin A deficiency and anemia are
      still important public health problems in Vietnam. Sustainable strategies for
      combating vitamin A deficiency and nutritional anemia are needed and should
      concentrate on target groups, especially infants and malnourished children in
      high risk regions.

PMID- 17215193
TI  - Vitamin A status of the minority ethnic group of Karen hill tribe children aged 1
      6 years in Northern Thailand.
AB  - Vitamin A deficiency (VAD) is the most common cause of childhood blindness in the
      developing world. It is estimated that by giving adequate vitamin A, in vitamin A
      deficient populations, child mortality from measles can be reduced by 50%, and
      mortality from diarrheal disease by 40%. Overall mortality in children 6-59
      months of age can be reduced by 23%. This paper reported results from a study of
      vitamin A status and malnutrition of the minority ethnic group of Karen hill
      tribe children aged 1-6 years in the north of Thailand. All children aged 1-6
      years (N = 158; 83 boys, 75 girls) from the three Karen villages (Mae Hae Tai,
      Mae Yot, Mae Raek) of Mae Chaem district in the north of Thailand were studied.
      The Karen is the largest mountain ethnic minority ("hill tribe") group in
      Thailand. All children were examined by a qualified medical doctor and were
      assessed for their vitamin A intakes using 24 hours dietary recall. Thai food
      composition table from Ministry of Health, Thailand were used as references. The
      results were compared with the Thai Recommended Dietary Allowances. Children aged
      1-3 years and 4-6 years were separately analysed due to the differences in Thai
      Recommended Dietary Allowances between the two age groups. A whole blood of 300
      microL was obtained by "fingerstick" for determination of serum vitamin A.
      Community or village's vitamin A status was assessed by using Simplified Dietary
      Assessment (SDA) method and Helen Keller International (HKI) food frequency
      method. Descriptive statistics were used to analyse the data. All families of the
      study boys and girls had income lower than the Thailand poverty line (US $
      1,000/year). On average, 63% of children from Mae Hae Tai village, 1.5% of
      children from Mae Yot village and none of children from Mae Raek village had
      serum vitamin A<0.7 micromol/L which indicated VAD. All boys and only girls from
      Mae Raek village consumed vitamin A more than the Thai RDA but girls from Mae Hae
      Tai village and Mae Yot village consumed vitamin A less than the Thai RDA. Both
      boys and girls from Mae Raek village and also girls from Mae Yot village consumed
      vitamin A more than the Thai RDA. Using SDA and HKI methods to assess vitamin A
      status of the villages to see whether VAD is a village's nutritional problem, it
      was found that all children from the three villages were at risk of VAD. In order
      to improve vitamin A status of the Karen children in Mae Chaem district,
      recommendations were made as follow: (1) increased use of fat and oil,
      particularly in areas with high risk of VAD; (2) more general work with Karen
      communities on how children's diets might be improved in a culturally acceptable
      manner, so as to bring vitamin A consumption closer to recommended allowance
      level.

PMID- 17215194
TI  - Decision to breastfeed and early cessation of breastfeeding in infants below 6
      months old--a population-based study of 3,204 infants in Hong Kong.
AB  - Breastfeeding rate has been low in Hong Kong over the last three decades. This
      has happened with concomitant rapid economic development and improved living
      standards. A population-based survey was conducted to evaluate factors
      influencing decision, duration and early cessation of breastfeeding in 3,204 full
      term healthy infants under 6 months throughout Hong Kong in 1993. A self
      administered questionnaire was used. The overall percentage of breastfed infants
      was particularly low (9.6%), 36.1%had already given up breastfeeding and were
      being formula-fed (FFBF), 54.3% have been exclusively formula-fed since birth.
      The proportion of breastfed infants in the 5th month was even lower than in the
      1st month (4.2% vs. 14.7%). Mothers who sustained breastfeeding tended to have
      parity >or =2, were less educated, housewives and residing in Hong Kong <5 years
      when compared to FFBF mothers (p<0.009). Husbands had a decisive role on wives
      initiating breastfeeding while health-professionals had an influence on early
      switching to FFBF (p<0.003). More breastfeeding mothers perceived breastfeeding
      benefits than FFBF mothers (p<0.03). The Cox proportional hazard model showed
      that mother's residency status >or =5-year (HR=2.4), working mothers (HR=1.5) and
      health-professionals' opinions (HR=1.5) were associated with an early cessation
      of breastfeeding (p<0.001). However, strengthening immunity (HR=0.67) and parity
      >or =2 (HR=0.72) helped sustain breastfeeding (p<0.001). To conclude, the
      proportion of breastfed infants was low in Hong Kong in the early 1990s. Major
      factors associated with the decision to breastfeed and early cessation of
      breastfeeding were identified which would help formulate an inter-disciplinary
      approach for promotion of breastfeeding up-to 6 months and beyond.

PMID- 17215195
TI  - Supplementation of baby formula with native inulin has a prebiotic effect in
      formula-fed babies.
AB  - OBJECTIVES: In this study we investigated the effects of native inulin on formula
      fed babies. The influence of inulin on the microbial composition, pH, consistency
      and amount of faeces, and on frequency of defecation was assessed. METHODS: In
      this study a daily dosage of 0.25 g/kg/d was used: 3 weeks of inulin consumption
      were inulin followed by 3 weeks without or vice versa. The study group consisted
      of 14 babies with an average age of 12.6 weeks (+/-6.4 weeks) and the average
      intake of inulin was 1.5 (+/-0.3) g/d. RESULTS: The consumption of inulin
      increased the content of Bifidobacterium and Lactobacillus in the faeces of
      formula-fed babies, without affecting the number of Bacteroides or the total
      anaerobic count. With inulin a trend for stools becoming softer and the amount of
      faeces increased significantly. Frequency of defecation was not affected by the
      consumption of inulin. No adverse effects were reported during the periods of
      inulin consumption. CONCLUSIONS: We conclude that with native inulin a prebiotic
      effect can be observed in formula-fed babies. Inulin may therefore be a useful
      ingredient in the formulation of baby formula to enhance the nutritional
      properties.

PMID- 17215196
TI  - Anthropometric and biochemical markers for nutritional risk among residents
      within an Australian residential care facility.
AB  - The risk of malnutrition is high among elderly population, yet few studies have
      measured indicators of nutritional status among Australian aged-care residents.
      To determine the relationship between nutritional status and bone density, hand
      grip strength, and the timed-up and go test, in a group of Australian aged-care
      residents. Anthropometric and biochemical analysis measured in subjects recruited
      to be part of a six month multivitamin supplementation study. One hundred and
      fifteen subjects participated (68% female). The mean (SD) age and body weight was
      80.2(10.6) years, and 66.5(15.0) kg, respectively. Eleven percent were
      underweight (body mass index, BMI, <or =20.0 kg/m(2)), and 20% were obese BMI >or
      =30 kg/m(2)). Low serum 25-hydroxy-vitamin D (25(OH)D, <or =50 nmol/L)
      concentrations were found among 79% of subjects. After adjustment for body
      weight, there was an association between serum 25(OH)D and bone density (heel
      ultrasound) (r=.204, p=.027). Low serum zinc <or =10.7 micromol/L) concentrations
      were found among 46% of subjects; this group had a slower timed up and go time
      compared with those with higher zinc concentrations (n=19, 44.6 +/- 5.6 seconds
      vs. n=27, 30.0 +/- 3.3 seconds, p=.020). There were no associations between
      nutritional markers and hand grip strength. In this group, more than (3/4) of
      subjects had low serum 25(OH)D, and 46% had low zinc concentrations. Serum
      25(OH)D was associated a lower bone density and zinc with a slower walking time.
      This indicates that the elderly in long term residential care facilities are at
      high risk for poor nutritional status, potentially increasing morbidity and
      mortality.

PMID- 17215197
TI  - Prevalence of diabetes mellitus and population attributable fractions for
      coronary heart disease and stroke mortality in the WHO South-East Asia and
      Western Pacific regions.
AB  - The aims of this study were to obtain the most recent representative data for the
      prevalence of diabetes in adult populations in the World Health Organisation's
      South-East Asia and Western Pacific regions and to quantify the contribution of
      diabetes to the burden of mortality from cardiovascular diseases in these
      regions. Previous reports indicate that there are 83 million individuals with
      diabetes in the Asia-Pacific region, but since many of the country-specific
      estimates were not from nationally representative studies, this figure may not
      accurately reflect the current burden of diabetes. Information on the prevalence
      of diabetes was obtained by searching Medline and government health websites.
      Data were available from 12 countries representing 78% of the total population of
      the Asia-Pacific region. Six of 10 countries with complete data reported a
      prevalence of diabetes exceeding those estimates currently cited by the World
      Health Organization; three of which have also already exceeded the World Health
      Organization projections for 2030. In the 12 countries in the region with
      nationally representative data, the prevalence of diabetes ranged from 2.6% to
      15.1%. Hazard ratios from the Asia Pacific Cohort Studies Collaboration were used
      to calculate population attributable fractions for diabetes for fatal
      cardiovascular diseases in the region. Population attributable fractions ranged
      from 2% to 12% for coronary heart disease, 1% to 6% for haemorrhagic stroke, and
      2% to 11% for ischaemic stroke. Accurate estimates of the prevalence of diabetes
      are of great importance and standard methods are needed for periodic surveillance
      across the Asia-Pacific region and elsewhere.

PMID- 17215198
TI  - Time-lag estimate between dietary intake and breast cancer mortality in Japan.
AB  - This study examines the relationship between the nutrient intake, including total
      dietary fiber (TDF) and fat, and the age-adjusted mortality from breast cancer
      (MBC) in Japanese females during the period from 1948 to 2000. The information
      for MBC in females was based on the data in Vital Statistics of Japan.
      Nutritional data were collected from the National Nutrition Survey reports. The
      data were analyzed by Pearson's correlation and a partial correlation, adjusting
      for the effect of reproductive factors. The time lag was estimated by measuring
      the strength of the linear relationship set up for a 0-35-year delay in mortality
      and statistically evaluated by comparing the correlation coefficients. The
      partial correlation analysis indicated that the individual intakes of total fat
      (r=0.688), animal protein (r=0.657), carbohydrate (r=-0.886), and plant protein
      (r=-0.770) were significantly (p<0.01) correlated with MBC. Each of these
      coefficients of correlation changed and reached a maximum value with increasing
      time lag. The estimated time lag values for the influence of fat, animal protein
      and TDF were 20-32 years, 19-31 years and 9-35 years, respectively. It is deduced
      from the results that the increased MBC in Japanese women is related to the long
      term effect from the intake of a high-fat, high-animal protein and low-fiber diet
      typical in the western world.

PMID- 17215199
TI  - Family caregiving to those with dementia in rural Alabama: racial similarities
      and differences.
AB  - This study explored differences and similarities in the experiences of African
      American and White family caregivers of dementia patients living in rural
      Alabama. This cross-sectional survey used a caregiving stress model to
      investigate the interrelationships between caregiving burden, mediators, and
      outcomes. Random-digit-dialing telephone interviews were used to obtain data on a
      probability sample of 74 non-Hispanic White and 67 African American caregivers.
      White caregivers were more likely to be married and older, used acceptance and
      humor as coping styles, and had fewer financial problems. African American
      caregivers gave more hours of care, used religion and denial as coping styles,
      and were less burdened. The authors have developed a methodology for obtaining a
      representative sample of African American and White rural caregivers. Further
      investigations are needed of the interactions between urban/rural location and
      ethnic/racial backgrounds of dementia caregivers for heuristic and applied
      reasons.

PMID- 17215200
TI  - Relationship of coping styles with quality of life and depressive symptoms in
      older heart failure patients.
AB  - This study examines the relationship between coping styles, quality of life, and
      depressive symptoms in older heart failure patients. Eighty heart failure
      patients seeking treatment in an outpatient heart failure or family practice
      clinic participated in a study examining depression, disability, and heart
      failure. Patients completed a clinical interview and questionnaires about mood,
      functional impairment, comorbid illness, quality of life, and coping. Heart
      failure severity and maladaptive coping styles, including denial, self
      distraction, and self-blame, negatively affected quality of life and depressive
      symptoms. The use of maladaptive coping strategies involves efforts that divert
      attention from the illness and suggests the need to provide heart failure
      patients the skills to directly address the stress associated with their illness.
      Interventions that target these coping strategies may help patients take a more
      active role in their heart failure management and may improve psychological and
      cardiac outcomes.

PMID- 17215201
TI  - Quality of life demands comprehension and further exploration.
AB  - The intention of this study was to elucidate what the concept "quality of life"
      means to elderly women. A qualitative approach based on 282 women (age 75-93
      years) showed that the participants were able to articulate what quality of life
      meant to them. Thinking about what makes for a good quality of life, 82.3%
      mentioned the importance of good social functioning, 68.8% mentioned good health,
      22.3% mentioned good economic circumstances, and 14.9% mentioned the importance
      of living in their own flat or house. Six categories were identified based on the
      women's descriptions: holism, relationships, activity and participation,
      pragmatic approach to health, belonging and social environment, and personal
      values. The lay perspective on quality of life is characterized by three
      qualities: preservation of continuity-sameness within change, power-empowerment,
      and the quest for meaning.

PMID- 17215202
TI  - Ethnic differences in self-rated health among older adults: a cross-sectional and
      longitudinal analysis.
AB  - The objectives of this study were to examine whether self-rated health differs
      among older adults of different ethnic backgrounds and to explore what factors
      may account for potential differences. The study was based on the 1983 and 1996
      waves of the Aging in Manitoba study. A self-report measure of ethnic background
      was used to categorize participants into four groups: British/Canadian,
      Northern/Central European, Eastern European, and Other. In both 1983 and 1996,
      older Eastern European adults had significantly reduced odds of rating their
      health as good or excellent relative to British/Canadian adults. Controlling for
      demographic variables, socioeconomic status, language spoken, and health status
      attenuated but did not eliminate the difference. Global, subjective ratings of
      health are frequently used to measure health. The ethnic differences found here
      suggest, however, that ratings may be influenced by cultural factors, which may
      warrant some caution in making comparisons across ethnic groups.

PMID- 17215203
TI  - Rural family caregivers and health behaviors: results from an epidemiologic
      survey.
AB  - This study examined health behaviors in a sample of rural family caregivers. In a
      community telephone survey of rural Missouri, Arkansas, and Tennessee,
      respondents were asked about their health, physical activity, nutrition, health
      providers, and family caregiving. Among 1,234 survey respondents, 12% self
      identified as family caregivers. Caregivers reported lower fruit intake, more
      walking for exercise, and more provider advice about stress, fruits, and
      vegetables than noncaregivers. Groups did not differ in smoking, dietary fat,
      obesity, or self-rated health. Women caregivers reported more favorable patterns
      of physical activity, smoking, and provider interactions than men caregivers, and
      White caregivers had healthier reports of physical activity and body mass index
      than Black caregivers. These results provide new information about rural
      caregivers' health habits. Apart from nutritional intake, caregivers were not
      significantly different in most health behaviors. However, health providers
      seemed more attentive to caregivers regarding nutrition and stress.

PMID- 17215204
TI  - Examining the association between lung functioning and cognitive performance in
      African American adults.
AB  - The current study examined the extent to which pulmonary functioning, as measured
      by average peak expiratory flow, was related to performance on seven cognitive
      measures. Analyses were conducted on a sample of 396 African American adults
      ranging in age from 22 to 89 years. RESULTS: Lung functioning was not uniquely
      associated with cognitive performance in the younger adults, though it emerged as
      a significant predictor of individual differences in performance on the Telephone
      Interview of Cognitive Status even after controlling for age, education, and
      smoking history. Biobehavioral assessments such as the one presented here appear
      to provide important new insights into the sources of individual differences in
      cognition observed in this understudied population.

PMID- 17215206
TI  - Predicting the changes in depressive symptomatology in later life: how much do
      changes in health status, marital and caregiving status, work and volunteering,
      and health-related behaviors contribute?
AB  - This study examined the unique effects of four variable groups on changes in
      older adults' depressive symptoms for a 2-year period: (1) baseline health and
      disability status, (2) changes in health and disability since baseline, (3)
      stability and changes in marital and caregiving status and in work and
      volunteering, and (4) stability and changes in health-related behaviors. With
      data from the 1998 and 2000 interview waves of the Health and Retirement Study,
      the authors used gender-separate multistep (hierarchical) residualized regression
      analyses in which the Center for Epidemiological Studies Depression scale (CES-D)
      score at follow-up is modeled as a function of the effect of each group of
      independent variables. As hypothesized, changes in health, disability, marital,
      and caregiving status explained a larger amount of variance than the existing and
      stable conditions, although each group of variables explained a relatively small
      amount (0.3-3.4%) of variance in the follow-up CES-D score.

PMID- 17215205
TI  - Three methods of assessing values for advance care planning: comparing persons
      with and without dementia.
AB  - Advance care planning ideally includes communication about values between
      patients, family members, and care providers. This study examined the utility of
      health care values assessment tools for older adults with and without dementia.
      Adults aged 60 and older, with and without dementia, completed three values
      assessment tools-open-ended, forced-choice, and rating scale questions-and named
      a preferred surrogate decision maker. Responses to forced-choice items were
      examined at 9-month retest. Adults with and without dementia appeared equally
      able to respond meaningfully to questions about values regarding quality of life
      and health care decisions. People with dementia were generally as able as
      controls to respond consistently after 9 months. Although values assessment
      methods show promise, further item and scale development work is needed. Older
      adults with dementia should be included in clarifying values for advance care
      planning to the extent that they desire and are able.

PMID- 17215207
TI  - Passive treatment of acid mine drainage in bioreactors using sulfate-reducing
      bacteria: critical review and research needs.
AB  - Acid mine drainage (AMD), characterized by low pH and high concentrations of
      sulfate and heavy metals, is an important and widespread environmental problem
      related to the mining industry. Sulfate-reducing passive bioreactors have
      received much attention lately as promising biotechnologies for AMD treatment.
      They offer advantages such as high metal removal at low pH, stable sludge, very
      low operation costs, and minimal energy consumption. Sulfide precipitation is the
      desired mechanism of contaminant removal; however, many mechanisms including
      adsorption and precipitation of metal carbonates and hydroxides occur in passive
      bioreactors. The efficiency of sulfate-reducing passive bioreactors is sometimes
      limited because they rely on the activity of an anaerobic microflora [including
      sulfate-reducing bacteria (SRB)] which is controlled primarily by the reactive
      mixture composition. The most important mixture component is the organic carbon
      source. The performance of field bioreactors can also be limited by AMD load and
      metal toxicity. Several studies conducted to find the best mixture of natural
      organic substrates for SRB are reviewed. Moreover, critical parameters for design
      and long-term operation are discussed. Additional work needs to be done to
      properly assess the long-term efficiency of reactive mixtures and the metal
      removal mechanisms. Furthermore, metal speciation and ecotoxicological assessment
      of treated effluent from on-site passive bioreactors have yet to be performed.

PMID- 17215208
TI  - Phosphorus leaching from cow manure patches on soil columns.
AB  - The loss of P in overland flow or leachate from manure patches can impair surface
      water quality. We studied leaching of P from 10-cm-high lysimeters filled with
      intact grassland soil or with acid-washed sand. A manure patch was created on two
      grassland and two sand-filled lysimeters, and an additional two grass lysimeters
      served as blanks. Lysimeters were leached in the laboratory during 234 d with a
      diluted salt solution, and column effluent was passed through a 0.45-microm
      filter, analyzed for pH, dissolved reactive P (DRP), and total dissolved P (TDP).
      At the end of the experiment lysimeter soil was sampled and analyzed for pH,
      available P, and oxalate-extractable P, Fe, and Al. The concentration of TDP in
      the effluent from the sand column increased to 25 mg L-1 during the first weeks
      and remained above 10 mg L-1 during the rest of the percolation. In effluent from
      grass + patch lysimeters TDP gradually increased to 4 mg L-1. Both in the manure
      and in the effluent of the sand lysimeter P was found mainly in the form of DRP,
      but in the effluent from the grass lysimeters was found mainly as dissolved
      unreactive P (DUP=TDP-DRP). Earthworm activity was responsible for decomposition
      of the manure patch on the grass lysimeters. Manure patches and their remains
      were found to be a long-term source of high concentrations of P in leachates.
      Spreading of patches after a grazing period could reduce their possible negative
      impacts on the environment.

PMID- 17215209
TI  - Organic agriculture and nitrous oxide emissions at sub-zero soil temperatures.
AB  - In the Red River Valley of the upper midwestern United States, soil temperatures
      often remain below freezing during winter and N2O emissions from frozen cropland
      soils is assumed to be negligible. This study was conducted to determine the
      strength of N2O emissions and denitrification when soil temperatures were below
      zero for a manure-amended, certified organic field (T2O) compared with an
      unamended, conventionally managed field (T2C). Before manure application, both
      fields were similar with respect to autotrophic and heterotrophic N2O production
      and N2O flux at the soil surface (0.15+/-0.05 mg N2O-N m-2 d-1 for T2O and 0.12+/
      0.06 mg N2O-N m-2 d-1 for T2C). After application of pelletized, dehydrated
      manure, average daily flux (based on time-integrated fluxes from 20 November to 8
      April), was 1.19+/-0.34 mg N2O-N m-2 d-1 for T2O and 0.47+/-0.37 mg N2O-N m-2 d-1
      for T2C. Denitrification for intact cores measured in the laboratory at -2.5
      degrees C was greater for organically managed soils, although only marginally
      significant (p<0.1). Cumulative emissions for all winter measurements (from 16
      November to 8 April) averaged 1.63 kg N2O-N ha-1 for T2O and 0.64 kg N2O-N ha-1
      for T2C. Biological N2O production was evident at sub-zero soil temperatures,
      with winter emissions exceeding those measured in late summer. Late autumn manure
      application enhanced cumulative N2O-N emissions by 0.9 kg ha-1.

PMID- 17215210
TI  - Risk assessment of unsuitable winter conditions for manure and nutrient
      application across Ontario.
AB  - Practical guidelines addressing the timing of manure and nutrient application
      must consider the concerns of the farm operators while ensuring the protection of
      the environment. An approach was developed and analyzed through case studies to
      determine the first recommended day in the spring, and the last in the fall, for
      manure and nutrient application based on probability analysis. Since most manure
      and nutrient application guidelines recommend avoiding adverse conditions, the
      three criteria established to perform a risk assessment were: (i) a frost depth
      greater than 0.05 m; (ii) a snow accumulation of greater than 0.05 m; and (iii) a
      soil volumetric water content greater than or equal to that of the plastic limit
      for the soil. Climatic data and typical soil information for seven locations in
      Ontario were used to model volumetric soil water contents, frost depths, and snow
      accumulation from the simultaneous heat and water (SHAW) model for a 48-yr period
      (1954-2001). Applying the three criteria to the modeled output, the average range
      between the least limiting probability (0.1, or one in ten year occurrence) and
      the greatest limiting probability (0.001, or one in one thousand year occurrence)
      analyzed among the locations was 16 d in the spring as compared to 29 d in the
      fall. Although geographical location affected the predicted spring start and fall
      end recommended manure and nutrient application dates, local climate and soil
      hydraulic properties also played an important part in the determination of these
      days. Overall the prediction method developed performed reasonably well and
      provided insight into the environmental factors influencing manure and nutrient
      application timing.

PMID- 17215211
TI  - Plant availability of zinc and copper in soil after contamination with brass
      foundry filter dust: effect of four years of aging.
AB  - We investigated the effect of 4 yr of aging of a noncalcareous soil contaminated
      with filter dust from a brass foundry (80% w/w ZnO, 15% w/w Cu0.6Zn0.4) on the
      chemical extractability of Zn and Cu and their uptake by barley (Hordeum vulgare
      L.), pea (Pisum sativum L.), and sunflower (Helianthus annus L.). Pot experiments
      were conducted with the freshly contaminated soil (2250 mg kg-1 Zn; 503 mg kg-1
      Cu), with the contaminated soil aged for 4 yr in the field (1811 mg kg-1 Zn; 385
      mg kg-1 Cu), and with the uncontaminated control soil (136 mg kg-1 Zn; 32 mg kg-1
      Cu). In comparison with the uncontaminated soil, the growth of barley and pea was
      clearly reduced in both contaminated soils, while toxicity symptoms did not
      systematically vary from the freshly contaminated to the 4 yr aged soil. The
      sunflower did not grow in the contaminated soils. The slow oxidative dissolution
      of the brass platelets led to an increase in the solubility and the plant uptake
      of Cu from the freshly contaminated to the 4 yr aged soil. In an earlier study,
      we found that the fine-grained ZnO dissolved in the field soil within 9 mo and
      that about half of the released Zn was incorporated into a layered double
      hydroxide phase and about half was adsorbed to the soil matrix. These changes in
      Zn speciation did not lead to a reduction of the Zn contents in the shoots and
      roots of barley and pea grown in the aged soil as compared with the freshly
      contaminated soil.

PMID- 17215212
TI  - Single-element and competitive metal mobility measured with column infiltration
      and batch tests.
AB  - The distribution coefficient, Kd, is often used to quantify heavy metal mobility
      in soils. Batch sorption or column infiltration tests may be used to measure Kd.
      The latter are closer to natural soil conditions, but are difficult to conduct in
      clays. This difficulty can be overcome by using a laboratory centrifuge. An
      acceleration of 2600 gravities was applied to columns of London Clay, an Eocene
      clay sub-stratum, and Cu, Ni, and Zn mobility was measured in centrifuge
      infiltration tests, both as single elements and in dual competition. Single
      element Kd values were also obtained from batch sorption tests, and the results
      from the two techniques were compared. It was found that Kd values obtained by
      batch tests vary considerably depending on the metal concentration, while
      infiltration tests provided a single Kd value for each metal. This was typically
      in the lower end of the range of the batch test Kd values. For both tests, the
      order of mobility was Ni>Zn>Cu. Metals became more mobile in competition than
      when in single-element systems: Ni Kd decreased 3.3 times and Zn Kd 3.4 times
      when they competed with Cu, while Cu decreased only 1.2 times when in competition
      with either Ni or Zn. Our study showed that competitive sorption between metals
      increases the mobility of those metals less strongly bound more than it increases
      the mobility of more strongly bound metals.

PMID- 17215213
TI  - Vertical distribution and speciation of trace metals in weathering flotation
      residues of a zinc/lead sulfide mine.
AB  - Sulfide-bearing mine tailings are a serious environmental problem around the
      world. In this study, the vertical distribution and speciation of Zn and Pb in
      the fine-grained flotation residues of a former sulfide ore mine in Germany were
      investigated to assess the inorganic weathering processes that effect the
      environmental risk arising from this site. Total metal contents were determined
      by X-ray fluorescence spectroscopy (XRF). Mobilizable fractions of Zn, Pb, Fe,
      and Mn were quantified by sequential chemical extractions (SCE). Furthermore, the
      speciation of Zn was analyzed by Zn K-edge extended X-ray absorption fine
      structure spectroscopy (EXAFS) to identify the residual Zn species. The
      variations in pH and inorganic C content show an acidification of the topsoil to
      pH 5.5. EXAFS results confirm that Zn is mainly bound in sphalerite in the
      subsoil and weathering reactions lead to a redistribution of Zn in the topsoil. A
      loss of 35% Zn and S from the topsoil compared with the parent material with 10 g
      kg-1 Zn and neutral pH has been observed. If acidification proceeds it will lead
      to a significant release of Zn, S, and Pb to the ground water. In contrast to Zn,
      Pb is enriched in the mobile fraction of the topsoil by more than a factor of two
      compared with the subsoil which contains a total of 2 g kg-1 Pb. Thus, the high
      bioavailability of Pb and the potential for Pb uptake by plants and animals
      currently represent the most severe threat for environmental health.

PMID- 17215214
TI  - Potentially toxic elements contamination in urban soils: a comparison of three
      European cities.
AB  - Studies on several cities around the world confirm that urban soils are subject
      to heavy anthropogenic disturbance. However, these surveys are difficult to
      compare due to a lack of common sampling and analytical protocols. In this study
      the soils of Ljubljana (Slovenia), Sevilla (Spain), and Torino (Italy) were
      extensively sampled and analyzed using common procedures. Results highlighted
      similarities across the cities, despite their differences in geography, size,
      climate, etc. Potentially toxic elements (PTE) showed a wide range in
      concentration reflecting a diffuse contamination. Among the "urban" elements Pb
      exceeded the legislation threshold in 45% of Ljubljana, 43% of Torino, and 11% of
      Sevilla samples while Zn was above the limits in 20, 43, and 2% of the soils of
      Ljubljana, Torino, and Sevilla, respectively. The distribution of PTE showed no
      depth-dependant changes, while general soil properties seemed more responsive to
      anthropogenic influences. Multivariate statistics revealed similar associations
      between PTE in the three cities, with Cu, Pb, and Zn in a group, and Ni and Cr in
      another, suggesting an anthropogenic origin for the former group and natural one
      for the latter. Chromium and Ni were unaffected by land use, except for roadside
      soils, while Cu, Pb, and Zn distribution appeared to be more dependent on the
      distance from emission sources. Regardless of the location, climate, and size,
      the "urban" factor--integrating type and intensity of contaminant emission and
      anthropogenic disturbance--seems to prevail in determining trends of PTE
      contamination.

PMID- 17215215
TI  - Denitrification in the shallow ground water of a tile-drained, agricultural
      watershed.
AB  - Nonpoint-source pollution of surface water by N is considered a major cause of
      hypoxia. Because Corn Belt watersheds have been identified as major sources of N
      in the Mississippi River basin, the fate and transport of N from midwestern
      agricultural watersheds have received considerable interest. The fate and
      transport of N in the shallow ground water of these watersheds still needs
      additional research. Our purpose was to estimate denitrification in the shallow
      ground water of a tile-drained, Corn Belt watershed with fine-grained soils. Over
      a 3-yr period, N was monitored in the surface and ground water of an agricultural
      watershed in central Illinois. A significant amount of N was transported past the
      tile drains and into shallow ground water. The ground water nitrate was
      isotopically heavier than tile drain nitrate, which can be explained by
      denitrification in the subsurface. Denitrifying bacteria were found at depths to
      10 m throughout the watershed. Laboratory and push-pull tests showed that a
      significant fraction of nitrate could be denitrified rapidly. We estimated that
      the N denitrified in shallow ground water was equivalent to 0.3 to 6.4% of the
      applied N or 9 to 27% of N exported via surface water. These estimates varied by
      water year and peaked in a year of normal precipitation after 2 yr of below
      average precipitation. Three years of monitoring data indicate that shallow
      ground water in watersheds with fine-grained soils may be a significant N sink
      compared with N exported via surface water.

PMID- 17215216
TI  - Fire effects on stable isotopes in a Sierran forested watershed.
AB  - This study tested the hypothesis that stable C and N isotope values in surface
      soil and litter would be increased by fire due to volatilization of lighter
      isotopes. The hypothesis was tested by: (1) performing experimental laboratory
      burns of organic and mineral soil materials from a watershed at combinations of
      temperature ranging 100 to 600 degrees C and duration ranging from 1 to 60 min;
      (2) testing field samples of upland soils before, shortly after, and 1 yr
      following a wildfire in the same watershed; and (3) testing field soil samples
      from a down-gradient ash/sediment depositional area in a riparian zone following
      a runoff event after the wildfire. Muffle furnace results indicated the most
      effective temperature range for using stable isotopes for tracing fire impacts is
      200 to 400 degrees C because lower burn temperatures may not produce strong
      isotopic shifts, and at temperatures>or=600 degrees C, N and C content of
      residual material is too low. Analyses of field soil samples were inconclusive:
      there was a slightly significant effect of the wildfire on delta15N values in
      upland watershed analyses 1 yr postburn, while riparian zone analyses results
      indicated that delta13C values significantly decreased approximately 0.71 per
      thousand over a 9 mo post-fire period (p=0.015), and ash/sediment layer delta13C
      values were approximately 0.65 per thousand higher than those in the A horizon.
      The lack of field confirmation may have been due to overall wildfire burn
      temperatures being <200 degrees C and/or microbial recovery and vegetative growth
      in the field. Thus, the muffle furnace experiment supported the hypothesis, but
      it is as yet unconfirmed by actual wildfire field data.

PMID- 17215217
TI  - Adsorption of 2,4-dichlorophenoxyacetic acid by an Andosol.
AB  - To identify the important soil components involved in 2,4-dichlorophenoxyacetic
      acid (2,4-D) adsorption on Andosols, 2,4-D adsorption on a surface horizon of an
      Andosol was compared with that on hydrogen peroxide (H2O2)-treated (soil organic
      matter [SOM] was removed), acid-oxalate (OX)-treated (active metal hydroxides and
      SOM were removed), and dithionite-citrate-bicarbonate (DCB)-treated (free and
      active metal [hydr]oxides and SOM were removed) soil samples at equilibrium pHs
      ranging from 4 to 8. Although the untreated soil contained a large amount of
      organic C (71.9 g kg-1), removal of SOM had little effect on 2,4-D adsorption.
      Active surface hydroxyls, which were attached to the active and free metal
      (hydr)oxides and metal SOM complexes, were identified as the most important soil
      functional group for 2,4-D adsorption. The dominant mechanism of the 2,4-D
      adsorption was a ligand exchange reaction in which the carboxylic group of 2,4-D
      displaced the active surface hydroxyl associated with metals and formed a strong
      coordination bond between the 2,4-D molecule and soil solid phase. The ligand
      exchange reaction reasonably accounted for the selective adsorption of 2,4-D over
      Cl-, competitive adsorption of phosphate over 2,4-D, reduction in plant-growth
      inhibitory activity of soil-adsorbed 2,4-D, and the high 2,4-D adsorption ability
      of Andosols. Although a humic acid purified from the soil did not adsorb 2,4-D,
      the presence of the humic acid increased 2,4-D adsorption on Al and Fe, probably
      by inhibiting the hydrolysis and polymerization of Al and Fe resulting in the
      preservation of available adsorption sites on these metals. The adsorption
      behavior of 2,4-D on soils could be a good index for predicting the adsorption
      behavior of other organic acids in soils.

PMID- 17215218
TI  - Surface seals reduce 1,3-dichloropropene and chloropicrin emissions in field
      tests.
AB  - Reducing emissions is essential for minimizing the impact of soil fumigation on
      the environment. Water application to the soil surface (or water seal) has been
      demonstrated to reduce 1,3-dichloropropene (1,3-D) emissions in soil column
      tests. This study determined the effectiveness of water application to reduce
      emissions of 1,3-D and chloropicrin (CP) in comparison to other surface seals
      under field conditions. In a small-plot field trial on a Hanford sandy loam soil
      (coarse-loamy, mixed, superactive, nonacid, thermic Typic Xerorthents) in the San
      Joaquin Valley, CA. Telone C35 (61% 1,3-D and 35% CP) was shank-applied at a
      depth of 46 cm at a rate of 610 kg ha-1. Soil surface seal treatments included
      control (no tarp and no water application), standard high density polyethylene
      (HDPE) tarp over dry and pre-irrigated soil, virtually impermeable film (VIF)
      tarp, initial water application by sprinklers immediately following fumigation,
      and intermittent water applications after fumigation. The atmospheric emissions
      and gas-phase distribution of fumigants in soil profile were monitored for 9 d.
      Among the surface seals, VIF and HDPE tarp over dry soil resulted in the lowest
      and the highest total emission losses, respectively. Intermittent water
      applications reduced 1,3-D and CP emissions significantly more than HDPE tarp
      alone. The initial water application also reduced emission peak and delayed
      emission time. Pre-irrigated soil plus HDPE tarp reduced fumigant emissions
      similarly as the intermittent water applications and also yielded the highest
      surface soil temperature, which may improve overall soil pest control.

PMID- 17215219
TI  - Effects of tree root-derived substrates and inorganic nutrients on pyrene
      mineralization in rhizosphere and bulk soil.
AB  - This study investigated the effects of organic and inorganic nutrients on the
      microbial degradation of the common soil contaminant pyrene. The material used in
      this investigation was collected from potted trees that had been growing for over
      a year in a soil artificially contaminated with polycyclic aromatic hydrocarbons.
      Soil was removed from the nonroot (bulk) and root (rhizosphere) zones of these
      pots and used in mineralization studies that tracked microbial degradation of 14C
      pyrene. The factors influencing degradation in these zones were then tested by
      amendment with essential inorganic nutrients or with root-derived materials. As
      expected, pyrene mineralization was greater in soil removed from the rhizosphere
      than in bulk soil. The rate of mineralization in rhizosphere soil was inhibited
      by inorganic nutrient amendment, whereas nutrients stimulated mineralization in
      the bulk soil. Pyrene mineralization in bulk soil was also increased by the
      addition of root extracts intended to mimic exudation by living roots. However,
      amendment with excised fine roots that were allowed to decay over time in soil
      initially inhibited mineralization. With time, the rate of mineralization
      increased, eventually exceeding that of unamended bulk soil. Combined, the
      initial inhibition and subsequent stimulation produced a zero net impact of
      decaying fine roots on bulk soil mineralization. Our results, in conjunction with
      known temporal patterns of fine root dynamics in natural systems, support the
      idea that seasonal variations in nutrient and substrate availability may
      influence the long-term effect of plants on organic degradation in soil, possibly
      reducing or negating the beneficial effects of vegetation that are often observed
      in short-term studies.

PMID- 17215220
TI  - Field history and dissipation of atrazine and metolachlor in Colorado.
AB  - Farmers in eastern Colorado have commented that atrazine does not provide the
      length of weed control that they expected in fields that have received multiple
      applications of the herbicide. Multiple laboratory studies suggest that atrazine
      dissipates more rapidly in soils with a history of atrazine use compared with
      soils that had not been treated with the herbicide and this could be related to
      the above observation. Field and laboratory studies were conducted to determine
      the rate of dissipation of atrazine and metolachlor in fields in Colorado. The
      published half-lives of atrazine and metolachlor are 60 and 56 d, respectively.
      In the field studies, the half-lives of atrazine and metolachlor in the top 15 cm
      of the soil ranged between 3.5 and 7.2 d and 17.9 and 18.8 d, respectively. In
      laboratory studies, the half-life of atrazine varied from 1.4 to 19.8 d with the
      shortest half-life occurring in soils which had been treated with atrazine for at
      least 5 yr. The longest half-life was in a soil that had never received atrazine.
      The half-life of metolachlor in these same soils varied from 10.6 to 28.2 d.
      There was no apparent relationship between the half-life of metolachlor and the
      half-life of atrazine in the laboratory studies. These results confirm farmers'
      observation of the shorter residual activity of atrazine in Colorado fields
      receiving atrazine over multiple years.

PMID- 17215221
TI  - Influence of decomposition on chemical properties of plant- and manure-derived
      dissolved organic matter and sorption to goethite.
AB  - Sorption of dissolved organic matter (DOM) plays an important role in maintaining
      the fertility and quality of soils in agricultural ecosystems. Few studies have
      examined the effects of decomposition on DOM sorption and chemical
      characteristics. This study investigated the sorption to goethite (alpha-FeOOH)
      of fresh and decomposed hydrophilic (HPL) and hydrophobic (HPB) DOM fractions
      extracted from the shoots and roots of crimson clover (Trifolium incarnatum L.),
      corn (Zea mays L.), soybean [Glycine max (L.) Merr.], hairy vetch (Vicia villosa
      L.), and dairy and poultry manures. Sorption was positively related to apparent
      molecular weight (MWAP), aromaticity as measured by absorptivity at 280 nm, and
      phenolic acid content. A 10-d laboratory microbial decomposition of the source
      organic matter generally increased the sorption of the extracted DOM onto
      goethite. The decomposition effect on sorption was greater for the HPL fractions
      than for the HPB fractions. There was a decrease in the MWAP values of the DOM
      samples following sorption to goethite. In many cases the reduction in MWAP was
      large, indicating a strong preference by goethite for the higher MWAP DOM
      fractions. The results of this laboratory-based research demonstrate that
      microbial processes affect the chemical characteristics of DOM which may affect
      the distribution of soil organic C pools.

PMID- 17215222
TI  - Relative effects of land use and near-stream chemistry on phosphorus in an urban
      stream.
AB  - Elevated levels of P in urban streams can pose significant water quality
      problems. Sources of P in urban streams, however, are difficult to identify. It
      is important to recognize both natural and anthropogenic sources of P. We
      investigated near-stream chemistry and land use factors on stream water P in the
      urbanizing Johnson Creek watershed in Portland, OR, USA. We sampled stream water
      and shallow groundwater soluble reactive P (SRP) and total P (TP) and estimated P
      flux at 13 sites along the main stem of Johnson Creek, with eight sites in urban
      land use areas and five sites in nonurban land use areas. At each site, we
      sampled the A and B horizons, measuring soil pH, water-soluble P, acid-soluble P,
      base-soluble P, total P, Fe, and Al. We found continuous input of P to the stream
      water via shallow groundwater throughout the Johnson Creek watershed. The shallow
      groundwater P concentrations were correlated with stream water P within the
      nonurban area; however, this correlation was not found in the urban area,
      suggesting that other factors in the urban area masked the relationship between
      groundwater P and stream water P. Aluminum and Fe concentrations were inversely
      correlated with shallow groundwater P, suggesting that greater P adsorption to Al
      and Fe oxides in the nonurban area reduced availability of shallow groundwater P.
      Using stepwise multiple regression analysis, however, we concluded that while
      riparian soil chemistry was related to stream water P, land use patterns had a
      more significant relationship with stream water P concentrations in this
      urbanizing system.

PMID- 17215223
TI  - Ground cover impacts on nitrogen export from manured riparian pasture.
AB  - Maintaining ground cover of forages may reduce the export of nitrogen (N) from
      pastures. The objective of this work was to determine the effect of ground cover
      on N export from pastured riparian areas receiving simulated rainfall. Plots were
      established on two adjacent sites in the North Carolina Piedmont: one of 10%
      slope with Appling sandy loam soils and a second of 20% slope with Wedowee sandy
      loam soils. Both sites had existing mixed tall fescue (Festuca arundinacea
      Schreb.)-dallisgrass (Paspalum dilatatum Poir.) vegetation. Forage stands were
      modified to represent a range of ground cover levels: 0, 45, 70, and 95% (bare
      ground, low, medium, and high cover, respectively), and amended with beef steer
      (Bos taurus) feces and urine (approximately 200 kg N ha-1). For all rain events
      combined, mean nitrate N export was greatest from bare ground and was reduced by
      34% at low cover, which did not differ from high cover. Mean ammonium N export
      was slightly elevated (approximately 1.37 kg N ha-1) in months when manures were
      applied and negligible (<0.02 kg N ha-1) in all other months. For all rain events
      combined, mean export of total N was greatest from bare ground and was reduced by
      at least 85% at all other cover levels. Whereas site did not impact N export,
      results indicated that cover and time of rainfall following manure deposition are
      important determinants of the impact of riparian grazing.

PMID- 17215224
TI  - Long-term effects of poultry litter, alum-treated litter, and ammonium nitrate on
      phosphorus availability in soils.
AB  - Alum (Al2(SO4)(3).14H2O) additions to poultry litter result in lower ammonia
      (NH3) volatilization and phosphorus (P) runoff; however, the long-term effects of
      alum on soil P behavior have been unknown. The objectives of this study were to
      evaluate the long-term effects of poultry litter, alum-treated litter, and
      ammonium nitrate (NH4NO3) on P availability in soils and P runoff. Two studies
      were initiated in 1995: a small plot (1.5x3.0 m) study and a paired watershed
      (0.405 ha) study. In the small plot study 13 treatments (control, four rates of
      normal litter, four rates of alum-treated litter, and four rates of NH4NO3) were
      applied to tall fescue (Festuca arundinacea Schreb.) plots. Results show that
      after 7 yr water-extractable P (WEP) in surface soil samples was greater with
      normal litter, but Mehlich III P was greater in surface soils fertilized with
      alum-treated litter. When soil samples were taken at depth intervals to 50 cm in
      Year 7, Mehlich III P was only greater in the surface 5 cm for soils fertilized
      with alum-treated litter. At lower depths Mehlich III P was greater with normal
      litter, and WEP was up to 288% greater when normal litter was used, indicating
      that alum significantly reduced P leaching. Uptake of P by fescue was not
      affected by alum. Results from the paired watershed study showed P loss in runoff
      was 340% greater for normal litter than for alum-treated litter. This research,
      combined with earlier work that shows alum use improves air and soil quality,
      supports the use of alum as a long-term solution to reducing P runoff and
      leaching.

PMID- 17215225
TI  - Five year-round forage systems in a dairy effluent sprayfield: phosphorus
      removal.
AB  - In northern Florida, forages are grown in dairy effluent sprayfields to recover
      excess P. Our purpose was to evaluate five year-round forage systems for their
      capacity to remove P from a dairy sprayfield. The soil is a Kershaw sand
      (thermic, uncoated Typic Quartzipsamment). Systems included bermudagrass (Cynodon
      spp.)-rye (Secale cereale L.) (BR), perennial peanut (Arachis glabrata Benth.)
      rye (PR), corn (Zea mays L.)-forage sorghum [Sorghum bicolor (L.) Moench]-rye
      (CSR), corn-bermudagrass-rye (CBR), and corn-perennial peanut-rye (CPR). Forages
      were grown for five 12-mo cycles. Effluent P rates were 80, 120, and 165 kg ha-1
      cycle-1. The 5-cycle P removal was 67 kg ha-1 cycle-1 for BR, 54 kg ha-1 for CBR,
      52 kg for CSR, 45 kg for PR, and 43 for CPR. Removal of P by winter rye was low.
      There were differences in system rankings among cycles primarily due to changes
      in the performance of perennial forages. In the first two cycles, BR had the
      greatest P removal (91 kg ha-1 cycle-1) due to high bermudagrass yield and P
      concentration. In the first cycle, P removal was lowest for PR (36 kg ha-1)
      because perennial peanut was slow to establish. In later cycles, P removal for BR
      declined because bermudagrass yield and P concentration declined. It increased
      for PR because peanut yield increased. The yield of corn in CBR, CPR, and CSR was
      consistently high but P concentration was modest (avg. 2.2 g kg-1). Sorghum
      produced moderate but stable yield and had low P levels (avg. 1.8 g kg-1).
      Effluent rate marginally affected the performance of most grasses. For P recovery
      in dairy sprayfields in northern Florida, the best warm-season forage would
      likely be a high yielding, persistent bermudagrass.

PMID- 17215226
TI  - Evaluation of zeolite for control of odorants emissions from simulated poultry
      manure storage.
AB  - Poultry operations are associated with emissions of aerial ammonia (NH3),
      volatile organic compounds (VOCs), and odor, and the magnitude of emissions is
      influenced by manure management practices. As a manure treatment additive,
      zeolites have been shown to have the potential to control NH3. Because of their
      properties it is also expected that zeolites could effectively adsorb VOCs and
      odor. The effectiveness of zeolite in controlling odor and VOCs was qualitatively
      evaluated in this controlled laboratory study involving simulated poultry manure
      storage. In the first two trials, zeolite was topically applied on nearly fresh
      laying hen manure at the rates of 0, 2.5, 5, and 10% (by weight). In the third
      trial, zeolite was topically applied at 5% with each addition of fresh manure
      into the storage vessel. Headspace samples from the emission vessels were
      collected with solid phase microextraction (SPME) and analyzed on a
      multidimensional-gas chromatograph-mass spectrometry-olfactometry (MDGC-MS-O)
      system for identification and prioritization of poultry manure odorants. Acetic
      acid, butanoic acid, isovaleric acid, indole, and skatole were consistently
      controlled in the headspace, with the reduction rate being proportional to the
      zeolite application rate. Dimethyl trisulfide and phenol were consistently
      generated, and with a few exceptions, the rate of generation was proportional to
      the application rate. Average reduction of the odor caused by all odorants
      evaluated with SPME-GC-O was 67% (+/-12%) and 51% (+/-26%) for the two topical
      applications, respectively, while no significant reduction of VOCs and odor was
      detected for the layered application.

PMID- 17215227
TI  - Substrate organic matter to improve nitrate removal in surface-flow constructed
      wetlands.
AB  - A wetland mesocosm experiment was conducted in eastern North Carolina to
      determine if organic matter (OM) addition to soils used for in-stream constructed
      wetlands would increase NO3--N treatment. Not all soils are suitable for wetland
      substrate, so OM addition can provide a carbon and nutrient source to the wetland
      early in its development to enhance denitrification and biomass growth. Four
      batch studies, with initial NO3--N concentrations ranging from 30 to 120 mg L-1,
      were conducted in 2002 in 21 surface-flow wetland mesocosms. The results
      indicated that increasing the OM content of a Cape Fear loam soil from 50 g kg-1
      (5% dry wt.) to 110 g kg-1 (11% dry wt.) enhanced NO3--N wetland treatment
      efficiency in spring and summer batch studies, but increases to 160 g kg-1 (16%
      dry wt.) OM did not. Wetlands constructed with dredged material from the USACE
      Eagle Island Confined Disposal Facility in Wilmington, NC, with initial OM of 120
      g kg-1 (12% dry wt.), showed no improvement in NO3--N treatment efficiency when
      increased to 180 g kg-1 (18% dry wt.), but did show increased NO3--N treatment
      efficiency in all batch studies when increased to 220 g kg-1 (22% dry wt.).
      Increased OM addition and biosolids to the Cape Fear loam and dredged material
      blends significantly increased biomass growth in the second growing season when
      compared to no OM addition. Results of this research indicate that increased OM
      in the substrate will reduce the area required for in-stream constructed wetlands
      to treat drainage water in humid regions. It also serves as a demonstration of
      how dredged material can be used successfully in constructed wetlands, as an
      alternative to costly storage by the USACE.

PMID- 17215229
TI  - Application of two organic wastes in a soil polluted by lead: effects on the soil
      enzymatic activities.
AB  - The effects of adding a crushed cotton gin compost (CCGC) and a poultry manure
      (PM) on the enzymatic activities of a Typic Xerofluvent soil polluted with Pb
      were studied in the laboratory. Three hundred grams of sieved soil (<2 mm) were
      mixed with PM at a rate of 10% or CCGC at a rate of 17.2%, applying to the soil
      the same amount of organic matter with each organic amendment. Urease, protease
      BBA, beta-glucosidase, alkaline phosphatase, and arylsulfatase activities were
      measured at four different incubation times (1, 7, 15, and 45 d) in soils
      containing seven concentrations (100, 250, 500, 1000, 2500, 5000, and 8000 mg kg
      1) of Pb, and in the same soils amended with CCGC and PM. In all treatments and
      incubation times, the inhibition percentage of soil enzyme activities by Pb was
      lower in soils amended with the PM and CCGC than in nonamended soils, and it
      differed with the organic amendment. In this respect, the in the 8000 mg Pb kg-1
      treatment at the end of the incubation period, the protease-BBA activity
      inhibition percentage was lower (14.7 and 33.9% lower, respectively) in CCGC-
      than in PM-amended soils. Since the adsorption capacity of Pb was higher in CCGC-
      than the PM-amended soils, the addition of organic wastes with higher humic acid
      concentration is more beneficial for remediation of soils polluted with Pb.

PMID- 17215228
TI  - Aerating grasslands: effects on runoff and phosphorus losses from applied broiler
      litter.
AB  - Aeration has been promoted as improving infiltration of rainfall and extending
      grass or forage productivity, but research on the impact of this practice on P
      losses from grasslands has had mixed results. We designed a study to determine at
      the field scale, using a paired watershed approach, the impact of slit aeration
      on runoff volume and P losses in runoff from fescue (Festuca arundinacea
      Schreb.)/bermudagrass (Cynodon dactylon L.) hay fields fertilized with broiler
      litter. Three pairs of 0.8-ha fields, each with similar soils (Typic
      Kanhapludults, Aquic Hapludults, and Aquultic Hapludalfs), were fertilized with
      broiler litter and monitored under similar management from 1995 through 1998,
      then one field in each pair received aeration treatment from 2001 through 2003.
      In the field with mostly well-drained soils, grassland aeration reduced surface
      runoff volume and mass losses of dissolved reactive P (DRP) in runoff by
      approximately 35%. In contrast, when poorly drained soils dominated, grassland
      aeration increased runoff volume (4.8 mm/runoff event) and mass losses of DRP and
      total P (0.25 kg TP ha-1 per runoff event). This implies that aeration of well
      drained soils in the top poultry-producing counties of Georgia (0.2 million ha)
      could decrease dissolved phosphorus losses by more than 500 Mg P each year. This
      is not the case if soils are poorly drained.

PMID- 17215230
TI  - Improving the accuracy of sediment-associated constituent concentrations in whole
      storm water samples by wet-sieving.
AB  - Sand-sized particles (>63 microm) in whole storm water samples collected from
      urban runoff have the potential to produce data with substantial bias and/or poor
      precision both during sample splitting and laboratory analysis. New techniques
      were evaluated in an effort to overcome some of the limitations associated with
      sample splitting and analyzing whole storm water samples containing sand-sized
      particles. Wet-sieving separates sand-sized particles from a whole storm water
      sample. Once separated, both the sieved solids and the remaining aqueous (water
      suspension of particles less than 63 microm) samples were analyzed for total
      recoverable metals using a modification of USEPA Method 200.7. The modified
      version digests the entire sample, rather than an aliquot, of the sample. Using a
      total recoverable acid digestion on the entire contents of the sieved solid and
      aqueous samples improved the accuracy of the derived sediment-associated
      constituent concentrations. Concentration values of sieved solid and aqueous
      samples can later be summed to determine an event mean concentration.

PMID- 17215231
TI  - Biosensing paraoxon in simulated environmental samples by immobilized
      organophosphorus hydrolase in functionalized mesoporous silica.
AB  - There is a critical need for highly sensitive, cost-effective sensors to conduct
      ecological analyses for environmental and homeland security-related applications.
      Enzyme biosensors, which are currently gaining acceptance for environmental
      monitoring applications, need improvements to deliver faster measurements with
      stabilized sensing elements, e.g., enzymes. We report here on a method which
      significantly overcomes this difficulty, and demonstrate its application in a
      biosensor for aquatic environmental applications. A fast-responding and stable
      biosensor was developed via immobilization of organophosphorus hydrolase (OPH) in
      functionalized mesoporous silica (FMS) with pore sizes in tens of nanometers. The
      OPH-FMS composite was held on glassy carbon electrode by a dried Nafion gel and
      FMS protected OPH from Nafion-resulted activity loss. The resulting enzyme
      biosensor, when integrated with an electrochemical instrument, responded rapidly
      to low paraoxon concentration and achieved steady-state current in less than 10
      s, with a detection limit of 4.0x10(-7) M paraoxon. The biosensor was tested for
      detection of paraoxon in simulated environmental samples, under wide-ranging
      physicochemical conditions. Results clearly indicate high recovery efficiencies
      in aqueous solutions (96 to 101%) at different pH, total organic carbon, total
      dissolved solids, and total suspended solids, and demonstrate the ability of the
      biosensor unit to continuously monitor paraoxon in aqueous conditions similar to
      those found in river and lake systems.

PMID- 17215232
TI  - Phytoremediation of polychlorinated biphenyl (PCB)-contaminated sediment: a
      greenhouse feasibility study.
AB  - Contaminated sediments dredged from navigable waterways often are placed in
      confined disposal facilities to prevent further spread of the pollutants.
      Reducing contaminants to acceptable levels would allow for disposal of the
      sediments and further dredging activity. A greenhouse study was conducted to
      evaluate plant treatments and the addition of an organic amendment to decrease
      the concentration of PCB congeners found in Arochlor 1260. Sediment treated with
      the amendment and either low transpiring plants or no plants had the greatest
      removal of the PCB congeners. High-transpiring plants apparently prevented the
      highly reducing conditions required for reductive dechlorination of highly
      chlorinated PCBs. Most likely, the amendment provided labile carbon that
      initiated the reducing conditions needed for dechlorination. The sediment
      moisture content and moisture-related plant parameters were significant
      predictors of the PCB loss. Carex aquatalis and Spartina pectinata are predicted
      to be the most effective plant treatments for phytoremediation of PCBs.

PMID- 17215233
TI  - Phytostabilization potential of quailbush for mine tailings: growth, metal
      accumulation, and microbial community changes.
AB  - Abandoned mine tailings sites in semiarid regions remain unvegetated for extended
      periods of time and are subject to eolian dispersion and water erosion. This
      study examines the potential phytostabilization of a lead-zinc mine tailings site
      using a native, drought-tolerant halophyte, quailbush [Atriplex lentiformis
      (Torr.) S. Wats.]. In a greenhouse study germination, growth, and metal uptake
      was evaluated in two compost-amended mine tailings samples, K4 (pH 3) and K6 (pH
      6) at 75, 85, 90, 95, and 100% mine tailings, and two controls, off-site and
      compost. Microbial community changes were monitored by performing MPN analysis of
      iron- and sulfur-oxidizing bacteria as well as heterotrophic plate counts.
      Results demonstrate that germination is not a good indicator for
      phytostabilization since it was only inhibited in the unamended K4 treatment.
      Plant growth was significantly reduced in 95 and 100% mine tailings, while growth
      in 75, 85, and 90% treatments was similar to the off-site control. Quailbush
      accumulated elevated levels of the nutrient metals Na, K, Mn, and Zn in the shoot
      tissues; however, metal accumulation was generally below the domestic animal
      toxicity limit. Initially, autotrophic population estimates were four to six logs
      higher than heterotrophic counts, indicating extremely stressed conditions.
      However, post-harvest, heterotrophic bacterial counts increased to normal levels
      (approximately 10(6) CFU g-1 dry tailings) and dominated the rhizosphere.
      Therefore, with compost amendment, quailbush has good potential as a native
      species candidate for phytostabilization of mine tailings in semiarid
      environments.

PMID- 17215234
TI  - Transformation of a landfill covering amended with municipal waste compost,
      Perugia, Italy.
AB  - This research deals with the transformation of an anthropomorphous landfill
      covering composed of a fill soil mixed with mechanically separated municipal
      waste compost. The study site was a municipal landfill near Perugia, Italy.
      Throughout the years, waste disposal in the landfill was performed by burial in
      horizontal layers, each one representing a yearly disposal. The external front of
      the landfill thus represented the yearly disposal over a 10-yr period starting in
      1993. Temporal changes in the anthropomorphous soil over this period were studied
      by examining and describing soil profiles, and by collecting and analyzing soil
      samples from the 1993, 1994, 1997, and 2001 disposals. The samples were subjected
      to a series of physical, chemical, and biochemical analyses. The results obtained
      suggest that over a 10-yr period the top layer gained a pedological structure
      (subangular blocky and/or crumb) giving rise to an A horizon. Improved soil
      structure was confirmed by an increase in macroporosity, particularly for pores
      larger than 50 microm, measured by image analysis of soil thin sections. Total
      extractable carbon showed an increase in the content of humic substances,
      evidenced by parameters of humification. Enzymatic activities in the A and C1
      horizons were also indicative of soil evolution and may serve as a valid
      indicator for monitoring the evolution of anthropogenic soils containing
      municipal waste compost.

PMID- 17215235
TI  - Use of ecosystem information to improve soil organic carbon mapping of a
      Mediterranean island.
AB  - Detailed maps of soil C are needed to guide sustainable soil uses and management
      decisions. The quality of soil C maps of Italian Mediterranean areas may be
      improved and the sampling density reduced using secondary data related to the
      nature of the ecosystem. The current study was conducted to determine: (i) the
      improvements obtainable in mapping soil C over a Mediterranean island by using
      ecosystem features and (ii) the effect of different sampling densities on the map
      accuracy. This work relied on field sampling (n=164) of soil properties measured
      over the island of Pianosa (Central Italy). Statistical analysis assessing the
      relationship between soil properties and ecosystem features revealed that the
      conceptual model of ecosystems defined on the basis of environmental features
      such as vegetation cover, land use, and soil type was mainly related to the
      variation of soil organic carbon (OC) content and to the type of Mediterranean
      environment. The distribution of ecosystems was used to improve the accuracy of
      soil OC maps obtainable by a simple interpolation approach (ordinary kriging).
      Substantial improvement was obtained by: (i) stratification into ecosystem types
      and (ii) applying locally calibrated regressions to satellite imagery that
      introduced both inter-ecosystem and intra-ecosystem information linked to
      vegetation features. This study showed that interpolation methods using
      information on ecosystem distribution can produce accurate maps of soil OC in
      Mediterranean environments, mostly because of the linkage between soil OC and
      vegetation types, which are spatially fragmented and heterogeneous.

PMID- 17215236
TI  - Accidental organochlorine pesticide contamination of soil in Porrino, Spain.
AB  - In the 1960s at Porrino, Spain, soil from a pesticide factory dump was placed in
      an uncontrolled land infill during demolition. Since then, organochlorine
      pesticides have degraded and migrated from their original location.
      Concentrations of lindane, DDT, dicofol, and related side products or degradation
      products were determined at depths of 0 to 20, 20 to 60 and 60 to 100 cm along a
      300-m transect running between the land infill and a nearby river. Depthwise
      nonmonotonicities (lowest concentrations of DDT and dicofol were found in the 20-
      to 60-cm layer) were attributed to the occurrence of several successive spill
      episodes; in general, concentrations were highest or near-highest in the 0- to 20
      cm layer. At the dump site, the analyte contents of the 0- to 20-cm layer were as
      follows: alpha-hexachlorocyclohexane (alpha-HCH), 25 mg kg-1; beta-HCH, 15 mg kg
      1; gamma-HCH (lindane), 1.3 mg kg-1; delta-HCH, 0.5 mg kg-1; DDT, 2.5 mg kg-1;
      dicofol, 0.05 mg kg-1; DDD+DDE, 2.2 mg kg-1. The alpha-HCH/gamma-HCH ratio was
      higher than in commercial products, and the DDT/(DDD + DDE) ratio lower,
      suggesting the degradation of lindane and DDT with time. In general, the
      concentrations of HCH isomers, DDT, and dicofol fell with increasing distance
      from the dump site; in particular, the rapid fall in HCH concentrations
      illustrates the marked immobility of these species in the soil. By contrast, the
      combined concentration of the DDT degradation products DDD and DDE rose with
      distance from the dump site, which is attributed to their higher mobility.

PMID- 17215237
TI  - Time-dependent distribution of surface-applied radionuclides and their recovery
      in maize during the growing season.
AB  - The spatial and temporal heterogeneity of field soils influences the fate and
      behavior of strongly sorbing pollutants and their entry into the food chain. We
      studied the redistribution of surface-applied 54Mn, 65Zn, 57Co, and 134Cs in the
      soil profile and their recovery in the aerial parts of maize grown on an untilled
      agricultural soil during the growing season. Radionuclides were more concentrated
      in the preferential flow paths (PFP) than in the soil matrix and their
      concentration decreased with time. The recovery of 54Mn in the aerial plant parts
      increased between pollen shed and maturity, while the recovery of 65Zn and 57Co
      did not show any significant difference, and the recovery of 134Cs decreased with
      time. The amount and distribution of rainfall, and the chemical, physical, and
      microbiological soil characteristics are the major factors influencing the
      variation of radionuclide recovery with time.

PMID- 17215238
TI  - Assessment of water quality and identification of pollution sources of plateau
      lakes in Yunnan (China).
AB  - The plateau lakes of Yunnan are important both ecologically and economically in
      China. Nevertheless, the human impact on water quality in these lakes has become
      increasingly highlighted. The water quality of 10 plateau lakes was monitored
      regularly over the period of 2000 through 2004 for 24 parameters. Multivariate
      statistical techniques, including cluster analysis (CA), factor analysis (FA),
      and principal component analysis (PCA), were employed to better interpret
      information about the water quality and its pollution sources. No obvious data
      reduction from CA/FA was found because three principal components (PCs) needed 14
      variables to explain 85.01% of the total variance. However, three latent factors
      accounted for pollution mainly from the following sources: agricultural
      activities, residential activities and anthropogenic-toxic pollution from
      industrial effluents, or other special activities. Box-whiskers plots were
      employed to visually interpret the spatiotemporal variations of water quality
      variables, which were highly correlated with three PCs. Three types of water
      quality (i.e., low-, medium-, and high-polluted lakes) were determined through CA
      based on the similarity of water quality variables. Our results may provide
      helpful information for the authorities to effectively manage the water quality
      and make sound policies.

PMID- 17215239
TI  - Influence of soil pH and application rate on the oxidation of calcium sulfite
      derived from flue gas desulfurization.
AB  - Calcium sulfite hemihydrate (CaSO(3).0.5H2O), a common byproduct of coal-fired
      utilities, is fairly insoluble and can decompose to release toxic SO2 under
      highly acidic soil conditions; however, it can also oxidize to form gypsum. The
      objective of this study was to examine the effects of application rate and soil
      pH on the oxidation of calcium sulfite under laboratory conditions. Oxidation
      rates measured by release of SO4-S to solution decreased with increasing
      application rate. Leachate SO4-S from soils amended with 1.0 to 3.0 g kg-1 CaSO3
      increased over a 21 to 28 d period before reaching a plateau. At 4 g kg-1,
      maximum SO4-S release was delayed until Week 7. Oxidation and release of SO4-S
      from soil amended with 3.0 g kg-1 calcium sulfite increased markedly with
      decreasing soil pH. After only 3 d incubation, the concentrations of SO4-S in
      aqueous leachates were 77, 122, 170, 220, and 229 mg L-1 for initial soil pH
      values of 7.8, 6.5, 5.5, 5.1, and 4.0, respectively. At an initial soil pH value
      of 4.0, oxidation/dissolution did not increase much after 3 d. At higher pH
      values, oxidation was maximized after 21 d. These results suggest that autumn
      surface applications of calcium sulfite in no-till systems should permit ample
      time for oxidation/dissolution reactions to occur without introducing biocidal
      effects related to oxygen scavenging. Soil and annual crops can thus benefit from
      additions of soluble Ca and SO4 if calcium sulfite is applied in advance of
      spring planting.

PMID- 17215240
TI  - Phosphorus movement and speciation in a sandy soil profile after long-term animal
      manure applications.
AB  - Long-term application of phosphorus (P) with animal manure in amounts exceeding
      removal with crops leads to buildup of P in soil and to increasing risk of P loss
      to surface water and eutrophication. In most manures, the majority of P is held
      within inorganic forms, but in soil leachates organic P forms often dominate. We
      investigated the mobility of both inorganic and organic P in profile samples from
      a noncalcareous sandy soil treated for 11 yr with excessive amounts of pig
      slurry, poultry manure, or poultry manure mixed with litter. Solution 31P nuclear
      magnetic resonance spectroscopy was used to characterize NaOH-EDTA-extractable
      forms of P, corresponding to 64 to 93% of the total P concentration in soil.
      Orthophosphate and orthophosphate monoesters were the main P forms detected in
      the NaOH-EDTA extracts. A strong accumulation of orthophosphate monoesters was
      found in the upper layers of the manure-treated soils. For orthophosphate,
      however, increased concentrations were found down to the 40- to 50-cm soil
      layers, indicating a strong downward movement of this P form. This was ascribed
      to the strong retention of orthophosphate monoesters by the solid phase of the
      soil, preventing orthophosphate sorption and facilitating downward movement of
      orthophosphate. Alternatively, mineralization of organic P in the upper layers of
      the manure-treated soils may have generated orthophosphate, which could have
      contributed to the downward movement of the latter. Leaching of inorganic P
      should thus be considered for the assessment and the future management of the
      long-term risk of P loss from soils receiving large amounts of manure.

PMID- 17215241
TI  - Long-term phosphorus immobilization by a drinking water treatment residual.
AB  - Excessive soluble P in runoff is a common cause of eutrophication in fresh
      waters. Evidence indicates that drinking water treatment residuals (WTRs) can
      reduce soluble P concentrations in P-impacted soils in the short term (days to
      weeks). The long-term (years) stability of WTR-immobilized P has been inferred,
      but validating field data are scarce. This research was undertaken at two
      Michigan field sites with a history of heavy manure applications to study the
      longevity of alum-based WTR (Al-WTR) effects on P solubility over time (7.5 yr).
      At both sites, amendment with Al-WTR reduced water-soluble P (WSP) concentration
      by >or=60% as compared to the control plots, and the Al-WTR-immobilized P (WTR-P)
      remained stable 7.5 yr after Al-WTR application. Rainfall simulation techniques
      were utilized to investigate P losses in runoff and leachate from surface soils
      of the field sites at 7.5 yr after Al-WTR application. At both sites, amendment
      with Al-WTR reduced dissolved P and bioavailable P (BAP) by >50% as compared to
      the control plots, showing that WTR-immobilized P remained nonlabile even 7.5 yr
      after Al-WTR amendment. Thus, WTR-immobilized P would not be expected to dissolve
      into runoff and leachate to contaminate surface waters or groundwater. Even if
      WTR-P is lost via erosion to surface waters, the bioavailability of the
      immobilized P should be minimal and should have negligible effects on water
      quality. However, if the WTR particles are destroyed by extreme conditions, P
      loss to water could pose a eutrophication risk.

PMID- 17215242
TI  - A model for phosphorus transformation and runoff loss for surface-applied
      manures.
AB  - Agricultural P transport in runoff is an environmental concern. An important
      source of P runoff is surface-applied, unincorporated manures, but computer
      models used to assess P transport do not adequately simulate P release and
      transport from surface manures. We developed a model to address this limitation.
      The model operates on a daily basis and simulates manure application to the soil
      surface, letting 60% of manure P infiltrate into soil if manure slurry with less
      than 15% solids is applied. The model divides manure P into four pools, water
      extractable inorganic and organic P, and stable inorganic and organic P. The
      model simulates manure dry matter decomposition, and manure stable P
      transformation to water-extractable P. Manure dry matter and P are assimilated
      into soil to simulate bioturbation. Water-extractable P is leached from manure
      when it rains, and a portion of leached P can be transferred to surface runoff.
      Eighty percent of manure P leached into soil by rain remains in the top 2 cm,
      while 20% leaches deeper. This 2-cm soil layer contributes P to runoff via
      desorption. We used data from field studies in Texas, Pennsylvania, Georgia, and
      Arkansas to build and validate the model. Validation results show the model
      accurately predicted cumulative P loads in runoff, reflecting successful
      simulation of the dynamics of manure dry matter, manure and soil P pools, and
      storm-event runoff P concentrations. Predicted runoff P concentrations were
      significantly related to (r2=0.57) but slightly less than measured
      concentrations. Our model thus represents an important modification for field or
      watershed scale models that assess P loss from manured soils.

PMID- 17215243
TI  - Denitrification potential and organic matter as affected by vegetation community,
      wetland age, and plant introduction in created wetlands.
AB  - Denitrification potential (DP) and organic matter (OM) in soils were compared in
      three different vegetation communities-emergent macrophyte, open water, and
      forested edge-in two 10-yr-old created riverine wetlands. Organic matter, cold
      water-extractable organic matter (CWEOM), anaerobic mineralizable carbon (AnMC),
      and DP varied significantly (P<0.05) among vegetation communities. The surface (0
      to 9 cm) soils in the emergent macrophyte community (EMC) showed highest DP
      (0.07+/-0.01 mg N h-1 kg-1), OM (84.90+/-5.60 g kg-1), CWEOM (1.12+/-0.20 g kg
      1), and AnMC (1.50+/-0.10 mg C h-1 kg-1). In the deeper layer (9 to 18 cm), DP
      and CWEOM (0.04+/-0.01 mg N h-1 kg-1 and 1.13+/-0.20 g kg-1, respectively) were
      significantly higher in the open water community (OWC) than in the emergent
      macrophyte and forested edge communities. Plant introduction did not affect DP or
      OM content and characteristics. After 10 yr of wetland development, mean DP
      increased 25-fold in the surface layer (from 0.002 to 0.053 mg N h-1 kg-1); OM
      content more than doubled to 90.80+/-19.22 g kg-1, and CWEOM and HWEOM increased
      2.5 and 2.7 times respectively from 1993 (prewetland conditions) to 2004. Humic
      acids were the most abundant form of OM in 2004 and 1993 samples. Significant
      (P<0.05) positive relationships between DP and OM, CWEOM, and AnMC were found in
      the surface layer; in the 9- to 18-cm layer, significant positive relationships
      were found between DP and CWEOM and AnMC.

PMID- 17215244
TI  - Purification and identification of G protein-coupled receptor protein complexes
      under native conditions.
AB  - G protein-coupled receptors (GPCRs) constitute the largest family of membrane
      receptors and are of major therapeutic importance. The identification of GPCR
      associated proteins is an important step toward a better understanding of these
      receptors. However, current methods are not satisfying as only isolated receptor
      domains (intracellular loops or carboxyl-terminal tails) can be used as "bait."
      We report here a method based on tandem affinity purification coupled to mass
      spectrometry that overcomes these limitations as the entire receptor is used to
      identify protein complexes formed in living mammalian cells. The human MT(1) and
      MT(2) melatonin receptors were chosen as model GPCRs. Both receptors were tagged
      with the tandem affinity purification tag at their carboxyl-terminal tails and
      expressed in human embryonic kidney 293 cells. Receptor solubilization and
      purification conditions were optimized. The method was validated by the co
      purification of G(i) proteins, which are well known GPCR interaction partners but
      which are difficult to identify with current protein-protein interaction assays.
      Several new and functionally relevant MT(1)- and MT(2)-associated proteins were
      identified; some of them were common to both receptors, and others were specific
      for each subtype. Taken together, our protocol allowed for the first time the
      purification of GPCR-associated proteins under native conditions in quantities
      suitable for mass spectrometry analysis.

PMID- 17215245
TI  - Loss of vacuolar proton-translocating ATPase activity in yeast results in chronic
      oxidative stress.
AB  - Yeast mutants lacking vacuolar proton-translocating ATPase (V-ATPase) subunits
      (vma mutants) were sensitive to several different oxidants in a recent genomic
      screen (Thorpe, G. W., Fong, C. S., Alic, N., Higgins, V. J., and Dawes, I. W.
      (2004) Proc. Natl. Acad. Sci. U. S. A. 101, 6564-6569). We confirmed that mutants
      lacking a V(1) subunit (vma2Delta), V(o) subunit, or either of the two V(o) a
      subunit isoforms are acutely sensitive to H(2)O(2) and more sensitive to
      menadione and diamide than wild-type cells. The vma2Delta mutant contains
      elevated levels of reactive oxygen species and high levels of oxidative protein
      damage even in the absence of an applied oxidant, suggesting an endogenous source
      of oxidative stress. vma2Delta mutants lacking mitochondrial DNA showed neither
      improved growth nor decreased sensitivity to peroxide, excluding respiration as
      the major source of the endogenous reactive oxygen species in the mutant. Double
      mutants lacking both VMA2 and components of the major cytosolic defense systems
      exhibited synthetic sensitivity to H(2)O(2). Microarray analysis comparing wild
      type and vma2Delta mutant cells grown at pH 5, permissive conditions for the
      vma2Delta mutant, indicated high level up-regulation of several iron uptake and
      metabolism genes that are part of the Aft1/Aft2 regulon. TSA2, which encodes an
      isoform of the cytosolic thioredoxin peroxidase, was strongly induced, but other
      oxidative stress defense systems were not induced. The results indicate that V
      ATPase activity helps to protect cells from endogenous oxidative stress.

PMID- 17215246
TI  - TrkA receptor activation by nerve growth factor induces shedding of the p75
      neurotrophin receptor followed by endosomal gamma-secretase-mediated release of
      the p75 intracellular domain.
AB  - Neurotrophins are trophic factors that regulate important neuronal functions.
      They bind two unrelated receptors, the Trk family of receptor-tyrosine kinases
      and the p75 neurotrophin receptor (p75). p75 was recently identified as a new
      substrate for gamma-secretase-mediated intramembrane proteolysis, generating a
      p75-derived intracellular domain (p75-ICD) with signaling capabilities. Using
      PC12 cells as a model, we studied how neurotrophins activate p75 processing and
      where these events occur in the cell. We demonstrate that activation of the TrkA
      receptor upon binding of nerve growth factor (NGF) regulates the metalloprotease
      mediated shedding of p75 leaving a membrane-bound p75 C-terminal fragment (p75
      CTF). Using subcellular fractionation to isolate a highly purified endosomal
      fraction, we demonstrate that p75-CTF ends up in endosomes where gamma-secretase
      mediated p75-CTF cleavage occurs, resulting in the release of a p75-ICD.
      Moreover, we show similar structural requirements for gamma-secretase processing
      of p75 and amyloid precursor protein-derived CTFs. Thus, NGF-induced endocytosis
      regulates both signaling and proteolytic processing of p75.

PMID- 17215247
TI  - The characterization and role of zinc binding in yeast Cox4.
AB  - Yeast Cox4 is a zinc binding subunit of cytochrome c oxidase. Cox4 is the only
      cofactor-containing subunit that is not directly part of the catalytic core of
      the enzyme located in the mitochondrial inner membrane. The Zn(II) site is shown
      to be distinct from the bovine ortholog, as it results from the x-ray structure
      of the entire cytochrome c oxidase in having a single histidyl residue and three
      conserved cysteines residues in the coordination sphere. Substitutions at the Cys
      ligand positions result in non-functional Cox4 proteins that fail to lead to
      cytochrome oxidase assembly. Limited function exists in His-119 mutants when
      overexpressed. Zn(II) binding in Cox4 is, therefore, important for the stability
      of the complex. The solution structure of yeast Cox4 elucidated by
      multidimensional NMR reveals a C-terminal globular domain consisting of two beta
      sheets analogous to the bovine ortholog except the loop containing the
      coordinating His in the yeast protein and the fourth Cys in the bovine protein
      are in different positions in the two structures. The conformation of this loop
      is dictated by the different sequence position of the fourth coordinating zinc
      ligand. The Zn(II) ion is buried within the domain, consistent with its role in
      structural stability. Potential functions of this matrix-facing subunit are
      discussed.

PMID- 17215248
TI  - A neural-specific F-box protein Fbs1 functions as a chaperone suppressing
      glycoprotein aggregation.
AB  - Fbs1 is an F-box protein present abundantly in the nervous system. Similar to the
      ubiquitously expressed Fbs2, Fbs1 recognizes N-glycans at the innermost position
      as a signal for unfolded glycoproteins, probably in the endoplasmic reticulum
      associated degradation pathway. Here, we show that the in vivo majority of Fbs1
      is present as Fbs1-Skp1 heterodimers or Fbs1 monomers but not SCF(Fbs1) complex.
      The inefficient SCF complex formation of Fbs1 and the restricted presence of
      SCF(Fbs1) bound on the endoplasmic reticulum membrane were due to the short
      linker sequence between the F-box domain and the sugar-binding domain. In vitro,
      Fbs1 prevented the aggregation of the glycoprotein through the N-terminal unique
      sequence of Fbs1. Our results suggest that Fbs1 assists clearance of aberrant
      glycoproteins in neuronal cells by suppressing aggregates formation, independent
      of ubiquitin ligase activity, and thus functions as a unique chaperone for those
      proteins.

PMID- 17215249
TI  - Ganglioside GM2-tetraspanin CD82 complex inhibits met and its cross-talk with
      integrins, providing a basis for control of cell motility through glycosynapse.
AB  - Glycosphingolipids (GSLs) at the cell surface membrane are associated or
      complexed with signal transducers (Src family kinases and small G-proteins),
      tetraspanins, growth factor receptors, and integrins. Such organizational
      framework, defining GSL-modulated or -dependent cell adhesion, motility, and
      growth, is termed "glycosynapse" (Hakomori, S., and Handa, K. (2002) FEBS Lett.
      531, 88-92; Hakomori, S. (2004) Ann. Braz. Acad. Sci. 76, 553-572). We describe
      here the functional organization of the glycosynaptic microdomain, and the
      mechanisms for control of cell motility and invasiveness, in normal bladder
      epithelial HCV29 cells versus highly invasive bladder cancer YTS1 cells, both
      derived from transitional epithelia. (i) Ganglioside GM2, but not GM3 or
      globoside, interacted specifically with tetraspanin CD82, and such a complex
      inhibited hepatocyte growth factor (HGF)-induced activation of Met tyrosine
      kinase in a dose-dependent manner. (ii) Depletion of GM2 in HCV29 cells by
      treatment with D-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (P4),
      or reduction of CD82 expression by RNA interference, significantly enhanced HGF
      induced Met tyrosine kinase and cell motility. (iii) In contrast, YTS1 cells,
      lacking CD82, displayed HGF-independent activation of Met tyrosine kinase and
      high cell motility. Transfection of the CD82 gene to YTS1 inhibited HGF dose
      dependent Met tyrosine kinase activity and cell motility, due to formation of the
      GM2-CD82 complex. (iv) Adhesion of YTS1 or YTS1/CD82 cells to laminin-5-coated
      plates, as compared with noncoated plates, strongly enhanced Met activation, and
      the degree of activation was further increased in association with GSL depletion
      by P4. Laminin-5-dependent Met activation was minimal in HCV29 cells. These
      findings indicate that GSL, particularly GM2, forms a complex with CD82, and that
      such complex interacts with Met and thereby inhibits HGF-induced Met tyrosine
      kinase activity, as well as integrin to Met cross-talk.

PMID- 17215250
TI  - Bone morphogenetic protein 2 activates Smad6 gene transcription through bone
      specific transcription factor Runx2.
AB  - BMP-2 plays an essential role in osteoblast and chondrocyte differentiation, but
      its signaling mechanism has not been fully defined. In the present studies, we
      investigated the mechanism through which BMP-2 activates the Smad6 gene. A 
      2006/+45 Smad6 promoter-luciferase construct was generated along with deletions
      and Runx2 binding site mutations to examine the role of Smad1 and Runx2 signaling
      following BMP-2 stimulation in osteoblasts. Transfection of Runx2 or treatment
      with BMP-2-stimulated promoter activity of the -2006/+45 and -1191/+45 reporters
      but not the -829/+45 and -374/+45 reporters. No Smad1/5 binding site is present
      in the -1191/-829 region of the Smad6 promoter. Mutation of the OSE2-a site (
      1036/-1031) completely abolished the stimulatory effect of Runx2 as well as BMP-2
      on the -2006/+45 and -1191/+45 Smad6 reporters. Gel shift and chromatin
      immunoprecipitation (ChIP) assays showed that Runx2 binds the OSE2-a element.
      ChIP assays demonstrated that Smad1 also interacts with the OSE2-a site at the
      Smad6 promoter through Runx2. The protein degradation of Runx2 is mediated by the
      E3 ubiquitin ligase Smurf1. In the present studies, we found that Smurf1 binds
      the OSE2-a site through Runx2 and inhibits Smad6 gene transcription. Treatment
      with BMP-2 and transfection of Smad1 abolished Smurf1 binding to the OSE2 site.
      These results show that Smad1 binding excludes Smurf1 interaction with the OSE2
      site and promotes Smad6 gene transcription.

PMID- 17215251
TI  - CD1d degradation in Chlamydia trachomatis-infected epithelial cells is the result
      of both cellular and chlamydial proteasomal activity.
AB  - Chlamydia trachomatis is an obligate intracellular pathogen that can persist in
      the urogenital tract. Mechanisms by which C. trachomatis evades clearance by host
      innate immune responses are poorly described. CD1d is MHC-like, is expressed by
      epithelial cells, and can signal innate immune responses by NK and NKT cells.
      Here we demonstrate that C. trachomatis infection down-regulates surface
      expressed CD1d in human penile urethral epithelial cells through proteasomal
      degradation. A chlamydial proteasome-like activity factor (CPAF) interacts with
      the CD1d heavy chain, and CPAF-associated CD1d heavy chain is then ubiquitinated
      and directed along two distinct proteolytic pathways. The degradation of immature
      glycosylated CD1d was blocked by the proteasome inhibitor lactacystin but not by
      MG132, indicating that degradation was not via the conventional proteasome. In
      contrast, the degradation of non-glycosylated CD1d was blocked by lactacystin and
      MG132, consistent with conventional cellular cytosolic degradation of N-linked
      glycoproteins. Immunofluorescent microscopy confirmed the interruption of CD1d
      trafficking to the cell surface, and the dislocation of CD1d heavy chains into
      both the cellular cytosol and the chlamydial inclusion along with cytosolic CPAF.
      C. trachomatis targeted CD1d toward two distinct proteolytic pathways. Decreased
      CD1d surface expression may help C. trachomatis evade detection by innate immune
      cells and may promote C. trachomatis persistence.

PMID- 17215252
TI  - In vivo characterization and therapeutic efficacy of a C5-specific inhibitor from
      the soft tick Ornithodoros moubata.
AB  - The involvement of complement (C) in inflammatory diseases has driven the search
      for agents capable of inhibiting dysregulated complement activation. Many of
      these reagents inhibit the C3 convertases during the early stages of the cascade.
      However, a drawback of total systemic C inhibition, particularly in longterm
      treatment of chronic disease, is potentiation of infection and immune complex
      disease due to an inability to opsonize complexes and foreign cells and to lyse
      pathogens. Recent identification of a C5-binding protein in the salivary gland of
      the soft tick Ornithodoros moubata has enabled development of a terminal pathway
      specific reagent, OmCI, with potential to ameliorate disease while leaving key
      physiological processes unaffected. Here we demonstrated that OmCI has broad
      cross-species activity. When given intravenously to rodents, OmCI totally ablated
      complement hemolytic activity, which gradually restored as C5 was resynthesized.
      The circulating half-life of OmCI was 30 h, demonstrating a much slower clearance
      than other small, biological agents. Using C5-sufficient and C5-deficient mice we
      showed that prolonged half-life was due to binding to plasma C5. Surface plasmon
      resonance analysis of C5 binding to OmCI confirmed a high binding affinity with a
      slow dissociation rate. OmCI was effective in preventing experimental autoimmune
      myasthenia gravis induced by passive transfer in normal Lewis rats. OmCI ablated
      clinical disease, reduced C3 and C9 deposition at the neuro-muscular junction,
      and effected a marked reduction in cellular infiltration at this site. These data
      offer exciting prospects for targeted treatment of complement-mediated diseases
      without the detrimental inhibition of the opsonic roles of complement.

PMID- 17215253
TI  - Kinetic and mutational analyses of the major cytosolic exopolyphosphatase from
      Saccharomyces cerevisiae.
AB  - Yeast exopolyphosphatase (scPPX) processively splits off the terminal phosphate
      group from linear polyphosphates longer than pyrophosphate. scPPX belongs to the
      DHH phosphoesterase superfamily and is evolutionarily close to the well
      characterized family II pyrophosphatase (PPase). Here, we used steady-state
      kinetic and binding measurements to elucidate the metal cofactor requirement for
      scPPX catalysis over the pH range 4.2-9.5. A single tight binding site for Mg(2+)
      (K(d) of 24 microm) was detected by equilibrium dialysis. Steady-state kinetic
      analysis of tripolyphosphate hydrolysis revealed a second site that binds Mg(2+)
      in the millimolar range and modulates substrate binding. This step requires two
      protonated and two deprotonated enzyme groups with pK(a) values of 5.0-5.3 and
      7.6-8.2, respectively. The catalytic step requiring two deprotonated groups
      (pK(a) of 4.6 and 5.6) is modulated by ionization of a third group (pK(a) of
      8.7). Conservative mutations of Asp(127), His(148), His(149) (conserved in scPPX
      and PPase), and Asn(35) (His in PPase) reduced activity by a factor of 600-5000.
      N35H and D127E substitutions reduced the Mg(2+) affinity of the tight binding
      site by 25-60-fold. Contrary to expectations, the N35H variant was unable to
      hydrolyze pyrophosphate, but markedly altered metal cofactor specificity,
      displaying higher catalytic activity with Co(2+) bound to the weak binding site
      versus the Mg(2+)- or Mn(2+)-bound enzyme. These results provide an initial step
      toward understanding the dynamics of scPPX catalysis and reveal significant
      functional differences between structurally similar scPPX and family II PPase.

PMID- 17215254
TI  - DnaK plays a pivotal role in Tat targeting of CueO and functions beside SlyD as a
      general Tat signal binding chaperone.
AB  - The Tat (twin-arginine translocation) system from Escherichia coli transports
      folded proteins with N-terminal twin-arginine signal peptides across the
      cytoplasmic membrane. The influence of general chaperones on Tat substrate
      targeting has not been clarified so far. Here we show that the chaperones SlyD
      and DnaK bind to a broad range of different Tat signal sequences in vitro and in
      vivo. Initially, SlyD and GroEL were purified from DnaK-deficient extracts by
      their affinity to various Tat signal sequences. Of these, only SlyD bound Tat
      signal sequences also in the presence of DnaK. SlyD and DnaK also co-purified
      with Tat substrate precursors, demonstrating the binding to Tat signal sequences
      in vivo. Deletion of dnaK completely abolished Tat-dependent translocation of
      CueO, but not of DmsA, YcdB, or HiPIP, indicating that DnaK has an essential role
      specifically for CueO. DnaK was not required for stability of the CueO precursor
      and thus served in some essential step after folding. A CueO signal sequence
      fusion to HiPIP was Tat-dependently transported without the need of DnaK,
      indicating that the mature domain of CueO is responsible for the DnaK dependence.
      The overall results suggest that SlyD and DnaK are in the set of chaperones that
      can serve as general Tat signal-binding proteins. DnaK has additional functions
      that are indispensable for the targeting of CueO.

PMID- 17215255
TI  - Chloroplast-encoded polypeptide PsbT is involved in the repair of primary
      electron acceptor QA of photosystem II during photoinhibition in Chlamydomonas
      reinhardtii.
AB  - PsbT is a small chloroplast-encoded hydrophobic polypeptide associated with the
      D1/D2 heterodimer of the photosystem II (PSII) reaction center and is required
      for the efficient post-translational repair of photodamaged PSII. Here we
      addressed that role in detail in Chlamydomonas reinhardtii wild type and
      DeltapsbT cells by analyzing the activities of PSII, the assembly of PSII
      proteins, and the redox components of PSII during photoinhibition and repair.
      Strong illumination of cells for 15 min decreased the activities of electron
      transfer through PSII and Q(A) photoreduction by 50%, and it reduced the amount
      of atomic manganese by 20%, but it did not affect the steady-state level of PSII
      proteins, photoreduction of pheophytin (pheo(D1)), and the amount of bound
      plastoquinone (Q(A)), indicating that the decrease in PSII activity resulted
      mainly from inhibition of the electron transfer from pheo(D1) to Q(A). In wild
      type cells, we observed parallel recovery of electron transfer activity through
      PSII and Q(A) photoreduction, suggesting that the recovery of Q(A) activity is
      one of the rate-limiting steps of PSII repair. In DeltapsbT cells, the repairs of
      electron transfer activity through PSII and of Q(A) photoreduction activity were
      both impaired, but PSII protein turnover was unaffected. Moreover, about half the
      Q(A) was lost from the PSII core complex during purification. Since PsbT is
      intimately associated with the Q(A)-binding region on D2, we propose that this
      polypeptide enhances the efficient recovery of Q(A) photoreduction by stabilizing
      the structure of the Q(A)-binding region.

PMID- 17215256
TI  - Calculating eGFR using the MDRD equation.

PMID- 17215257
TI  - The lectin domains of polypeptide GalNAc-transferases exhibit carbohydrate
      binding specificity for GalNAc: lectin binding to GalNAc-glycopeptide substrates
      is required for high density GalNAc-O-glycosylation.
AB  - Initiation of mucin-type O-glycosylation is controlled by a large family of UDP
      GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-transferases). Most
      GalNAc-transferases contain a ricin-like lectin domain in the C-terminal end,
      which may confer GalNAc-glycopeptide substrate specificity to the enzyme. We have
      previously shown that the lectin domain of GalNAc-T4 modulates its substrate
      specificity to enable unique GalNAc-glycopeptide specificities and that this
      effect is selectively inhibitable by GalNAc; however, direct evidence of
      carbohydrate binding of GalNAc-transferase lectins has not been previously
      presented. Here, we report the direct carbohydrate binding of two GalNAc
      transferase lectin domains, GalNAc-T4 and GalNAc-T2, representing isoforms
      reported to have distinct glycopeptide activity (GalNAc-T4) and isoforms without
      apparent distinct GalNAc-glycopeptide specificity (GalNAc-T2). Both lectins
      exhibited specificity for binding of free GalNAc. Kinetic and time-course
      analysis of GalNAc-T2 demonstrated that the lectin domain did not affect transfer
      to initial glycosylation sites, but selectively modulated velocity of transfer to
      subsequent sites and affected the number of acceptor sites utilized. The results
      suggest that GalNAc-transferase lectins serve to modulate the kinetic properties
      of the enzymes in the late stages of the initiation process of O-glycosylation to
      accomplish dense or complete O-glycan occupancy.

PMID- 17215260
TI  - Guidelines causing iatrogenic disease?

PMID- 17215261
TI  - Classification criteria for rheumatoid arthritis--time to abandon rheumatoid
      factor?

PMID- 17215262
TI  - Progressive osseous heteroplasia: a rare case of late onset.

PMID- 17215263
TI  - Acupuncture treatment for chronic knee pain: a systematic review.
AB  - OBJECTIVES: To evaluate the effects of acupuncture on pain and function in
      patients with chronic knee pain. METHODS: Systematic review and meta-analysis of
      randomized controlled trials of adequate acupuncture. Computerized databases and
      reference lists of articles were searched in June 2006. Studies were selected in
      which adults with chronic knee pain or osteoarthritis of the knee were randomized
      to receive either acupuncture treatment or a control consisting of sham (placebo)
      acupuncture, other sham treatments, no additional intervention (usual care), or
      an active intervention. The main outcome measures were short-term pain and
      function, and study validity was assessed using a modification of a previously
      published instrument. RESULTS: Thirteen RCTs were included, of which eight used
      adequate acupuncture and provided WOMAC outcomes, so were combined in meta
      analyses. Six of these had validity scores of more than 50%. Combining five
      studies in 1334 patients, acupuncture was superior to sham acupuncture for both
      pain (weighted mean difference in WOMAC pain subscale score = 2.0, 95% CI 0.57
      3.40) and for WOMAC function subscale (4.32, 0.60-8.05). The differences were
      still significant at long-term follow-up. Acupuncture was also significantly
      superior to no additional intervention. There were insufficient studies to
      compare acupuncture with other sham or active interventions. CONCLUSIONS:
      Acupuncture that meets criteria for adequate treatment is significantly superior
      to sham acupuncture and to no additional intervention in improving pain and
      function in patients with chronic knee pain. Due to the heterogeneity in the
      results, however, further research is required to confirm these findings and
      provide more information on long-term effects.

PMID- 17215264
TI  - Development of a DNA chip for the diagnosis of the most common corneal
      dystrophies caused by mutations in the betaigh3 gene.
AB  - AIM: To develop a diagnostic DNA chip to detect mutations in the betaigh3 gene
      causing the most common corneal dystrophies (CDs). METHODS: Samples from 98
      people, including patients with betaigh3-associated CDs (beta-aCDs), were
      examined. Specific primer and probe sets were designed to examine exons 4 and 12
      of the betaigh3 gene, in order to identify mutant and wild-type alleles.
      Mutations were then identified by hybridisation signals of sequence-specific
      probes immobilised on the slide glass. RESULTS: Direct sequencing of exons 4 and
      12 of the betaigh3 gene in the patients' genome showed that beta-aCDs could be
      mainly classified into five types: homozygotic Avellino corneal dystrophy (ACD),
      heterozygotic ACD, heterozygotic lattice CD I, heterozygotic Reis-Bucklers CD and
      heterozygotic granular CD. Blind tests were performed by applying the target DNA
      amplified from the genomic DNA isolated from the peripheral blood of the
      participants onto a DNA chip. The results obtained by DNA chip hybridisation
      matched well with the direct DNA sequencing results. CONCLUSIONS: The DNA chip
      developed in this study allowed successful detection of beta-aCDs with a
      sensitivity of 100%. Mutational analysis of exons 4 and 12 of the betaigh3 gene,
      which are the mutational hot spots causing beta-aCDs, can be successfully
      performed with the DNA chip. Thus, this DNA chip-based method should allow a
      convenient, yet highly accurate, diagnosis of beta-aCDs, and can be further
      applied to diagnose other types of CDs.

PMID- 17215265
TI  - Decreased retinal nerve fibre layer thickness detected by optical coherence
      tomography in patients with ethambutol-induced optic neuropathy.
AB  - BACKGROUND: It is difficult to assess the degree of optic nerve damage in
      patients with ethambutol-induced optic neuropathy, especially just after the
      onset of visual loss, when the optic disc typically looks normal. AIM: To
      evaluate changes in retinal nerve fibre layer thickness (RNFLT) using optical
      coherence tomography (OCT) in patients with optic neuropathy within 3 months of
      cessation of ethambutol treatment. DESIGN: A retrospective observational case
      series from a single neuro-ophthalmology practice. METHODS: 8 patients with a
      history of ethambutol-induced optic neuropathy were examined within 3 months
      after stopping ethambutol treatment. All patients underwent a neuro
      ophthalmologic examination, including visual acuity, colour vision, visual fields
      and funduscopy. OCT was performed on both eyes of each patient using the retinal
      nerve fibre layer analysis protocol. RESULTS: The interval between cessation of
      ethambutol treatment and the initial visit ranged from 1 week to 3 months. All
      patients had visual deficits characteristic of ethambutol-induced optic
      neuropathy at their initial visit, and the follow-up examination was performed
      within 12 months. Compared with the initial RNFLT, there was a statistically
      significant decrease in the mean RNFLT of the temporal, superior and nasal
      quadrants (p = 0.009, 0.019 and 0.025, respectively), with the greatest decrease
      in the temporal quadrant (mean decrease 26.5 mum). CONCLUSIONS: A decrease in
      RNFLT is observed in all quadrants in patients with ethambutol-induced optic
      neuropathy who have recently discontinued the medication. This decrease is most
      pronounced in the temporal quadrant of the optic disc.

PMID- 17215266
TI  - The effect of human in vivo accommodation on crystalline lens stability.
AB  - AIM: To determine the effect of human in vivo accommodation on the stability of
      the crystalline lens. METHODS: Using a dual Purkinje image (DPI) eyetracker, the
      phase-time difference and amplitudes of Purkinje images I (P(I)) and IV (P(1V))
      were measured in 37 normal emmetropic subjects (34 women and 3 men; mean age
      19.8, range 18-22 years) when they changed focus from 70 to 15 cm and
      simultaneously rotated their heads horizontally from side to side or made
      horizontal saccades between two targets 6.8 degrees apart. RESULTS: When the
      subjects changed focus from 70 to 15 cm and rotated their heads or made eye
      saccades, the phase-time difference between P(I) and P(IV) decreased. During
      saccades, the amplitude of both P(I) and P(IV) overshoots significantly increased
      with focus at 15 cm; however, their ratio (P(IV) overshoot amplitude/P(I)
      overshoot amplitude) significantly declined. CONCLUSIONS: The lens is stable
      during accommodation. The implications of these findings on the mechanism of
      accommodation are discussed.

PMID- 17215267
TI  - Glaucoma detection with matrix and standard achromatic perimetry.
AB  - BACKGROUND: Matrix perimetry is a new iteration of frequency-doubling technology
      (FDT) which uses a smaller target size in the standard achromatic perimetry
      presentation pattern. AIM: To compare the performance of matrix and Swedish
      interactive thresholding algorithm (SITA) perimetry in detecting glaucoma
      diagnosed by structural assessment. DESIGN: Prospective cross-sectional study.
      METHODS: 76 eyes from 15 healthy subjects and 61 consecutive glaucoma suspects
      and patients with glaucoma were included. All patients underwent optic nerve head
      (ONH) photography, SITA and matrix perimetries, and optical coherence tomography
      (OCT) within a 6-month period. Glaucoma diagnosis was established by either
      glaucomatous optic neuropathy or OCT by assessing retinal nerve fibre layer
      (RNFL) thickness. Mean deviation (MD), pattern standard deviation (PSD), glaucoma
      hemifield test and cluster of abnormal testing locations were recorded from
      matrix and SITA perimetries. RESULTS: Similar correlations were observed with
      matrix and SITA perimetry MD and PSD with either cup-to-disc ratio or OCT mean
      RNFL. The area under the receiver operating characteristic (AROC) curves of MD
      and PSD for discriminating between healthy and glaucomatous eyes ranged from 0.69
      to 0.81 for matrix perimetry and from 0.75 to 0.77 for SITA perimetry. There were
      no significant differences among any corresponding matrix and SITA perimetry
      AROCs. CONCLUSIONS: Matrix and SITA perimetries had similar capabilities for
      distinguishing between healthy and glaucomatous eyes regardless of whether the
      diagnosis was established by ONH or OCT-RNFL assessment.

PMID- 17215268
TI  - Residual indocyanine green fluorescence pattern after vitrectomy for idiopathic
      macular hole with internal limiting membrane peeling.
AB  - BACKGROUND: Internal limiting membrane (ILM) peeling with indocyanine green (ICG)
      staining is a commonly used procedure to treat idiopathic macular holes (MH).
      AIM: To report changes in the patterns of residual ICG fluorescence over time
      after vitrectomy using the Heidelberg Retina Angiograph 2 (HRA2, Heidelberg
      Engineering, Heidelberg, Germany). METHODS: 10 patients (10 eyes) who had
      undergone vitrectomy for MH with ILM peeling were included. 9 (90%) patients
      underwent ILM peeling with ICG, and 1 (10%) patient had it with triamcinolone
      acetonide (TA). We observed residual ICG using HRA2, postoperatively.
      Autofluorescence, optical coherence tomography images and best-corrected visual
      acuity (BCVA) measurements were also obtained. The minimal follow-up was 3
      months. RESULTS: The MHs were closed postoperatively in all patients (100%). In
      eyes that underwent ILM peeling with ICG, the BCVA improved significantly
      (p<0.001) in 8 (89%) eyes and was unchanged in 1 (11%) eye. HRA2 showed the ICG
      fluorescence patterns but not TA postoperatively. The ICG hyperfluorescent signal
      was typically diffuse at the posterior retina and was hypofluorescent around the
      fovea. The hyperfluorescence then migrated towards the optic nerve disc
      presumably along the nerve fibre, and the area of ILM peeling was clearly
      identified. A large number of hyperfluorescent dots were observed instead of
      diffuse hyperfluorescence that was observed just after surgery. CONCLUSIONS:
      Patterns of residual ICG fluorescence were sequentially observed with HRA2 after
      vitrectomy for MH with ICG-assisted ILM peeling.

PMID- 17215269
TI  - Continued use of dorzolamide for the treatment of cystoid macular oedema in
      patients with retinitis pigmentosa.
AB  - AIM: To determine the value of a topical carbonic anhydrase inhibitor for
      extended treatment of cystoid macular oedema (CME) in patients with retinitis
      pigmentosa (RP). METHOD: Eight patients with RP and foveal cystic-appearing
      lesions observed on fundus examination and by optical coherence tomography (OCT)
      testing were treated with a topical form of carbonic anhydrase inhibitor.
      RESULTS: Foveal cystic-like spaces were documented by OCT testing in all eight
      patients before treatment. All patients had a significant reduction in their
      foveal thickness (FT) and foveal zone thickness (FZT) in at least one eye after
      using 2% dorzolamide three times a day for 1 or 2 months. Six patients had an
      improvement in both eyes. After an additional 6-13 months of the same treatment
      regimen, out of six patients who had a sustained reduction in FT and FZT in at
      least one eye, four had this reduction in both eyes. While they were still taking
      Trusopt, a recurrence (rebound) of CME in both eyes was observed in two patients,
      whereas one patient had a sustained improvement in one eye and rebound of CME in
      the other eye. Out of 8 patients, 3 showed an improvement in their visual acuity
      by > or =7 letters, in at least one eye, on Snellen acuity charts, which was
      determined as clinically significant. CONCLUSION: Results from this study suggest
      that patients with RP could potentially sustain a beneficial effect from
      continued treatment with a topical form of carbonic anhydrase inhibitor.

PMID- 17215270
TI  - Senescence in cultured trabecular meshwork cells.
AB  - BACKGROUND: It has been suggested that replicative senescence might be involved
      in the pathophysiology of age-related diseases. AIM: To study the process of
      senescence in trabecular meshwork (TM) cells. METHODS: Porcine TM tissues were
      obtained and placed in primary cultures with Dulbecco's modified Eagle's
      medium/Ham's F-12 medium. After 2-3 weeks, migrated and proliferated TM cells
      were trypsinised and cultured in serial passages, and identified with fluorescein
      labelled low-density lipoprotein (DiI-Ac-LDL), a marker of TM cells. Staining for
      senescence-related beta-galactosidase activity was performed at population
      doubling level (PDL) 2, 8 and 16 at pH 6. Terminal restriction fragment (TRF)
      length was examined by Southern blot analysis using a (32)P-labelled telomere
      specific sequence (TTAGGG)(3) at each PDL. RESULTS: DiI-Ac-LDL staining revealed
      that most (nearly 100%) of the cells in the culture were TM cells, which were
      flattened in shape and positive for senescence-related beta-galactosidase
      staining at PDL 16. Reduction of TRF length as a function of population doubling
      was also shown. CONCLUSIONS: TM cells exhibited characteristics of senescence at
      PDL 16 in vitro. The results demonstrated that cellular senescence may be related
      to the pathophysiology of primary open-angle glaucoma.

PMID- 17215272
TI  - Appropriate evaluation of HIV prevention interventions: from experiment to full
      scale implementation.
AB  - BACKGROUND: Preventing HIV infection is still an essential goal in tackling the
      HIV/AIDS pandemic. Remarkably little is known about how best to reduce HIV
      incidence because most trials focus on the reduction of risk behaviours and
      assume an effect on HIV incidence. OBJECTIVE: To discuss the evidence for the
      effectiveness of HIV prevention strategies, exploring the different types of
      evidence available: individual and community randomised controlled trials, and
      observational studies. RESULTS: Although providing a gold standard for evidence,
      trials have been limited in their scope and are difficult to interpret and
      generalize. There have been examples of national level successes in preventing
      HIV which have been detected in surveillance data and understood through
      behavioural and modelling studies. These have the advantage of being to scale and
      indicating effectiveness rather than efficacy. CONCLUSIONS: Although randomised
      trials are important because of their scientific rigor, it is also important that
      evidence from observational epidemiology is not overlooked. Only if good quality,
      consistent data are available can the history of the HIV epidemic be
      appropriately analysed.

PMID- 17215273
TI  - Evaluating the proximate determinants framework for HIV infection in rural
      Zimbabwe.
AB  - BACKGROUND: Risk factors for HIV infection can act at one of several causal
      levels, making interpretation of results problematic. One suggested solution has
      been a proximate determinants framework, in which risk factors are grouped into
      "underlying", "proximate" and "biological" determinants. METHODS: A baseline,
      cross-sectional survey of HIV serostatus and potential risk factors was carried
      out among 9480 adults in Zimbabwe. Associations were assessed separately for men
      and women using logistic regression models; data were only included for those who
      reported sexual debut. The predictive ability of proximate determinants
      describing both individual and partnership characteristics was assessed along
      with that of the underlying determinants. The significance of the underlying
      determinants once adjusted for proximate determinants was then evaluated.
      Finally, the relationship between the underlying determinants and some of the key
      proximate determinants was explored. RESULTS: The two most important proximate
      determinants for men and women were lifetime number of sexual partners and
      symptoms of sexually transmitted infections (p<0.001). After adjustment for all
      proximate determinants, some underlying determinants were still significant,
      particularly age group, marital status and community (p<0.001). CONCLUSIONS:
      Although proximate determinants could explain the action of many underlying
      determinants, several of the latter remained significant after adjustment for the
      proximate determinants. Hence, the proximate determinants were probably not
      measured completely. An important determinant of an individual's risk of HIV
      infection is the HIV status of their sexual partners. This was not measured in
      this survey, and may be related to the individual's age (as a predictor for the
      age of the partner), marital status and community prevalence. However, it will be
      measured in a subsequent survey of this cohort.

PMID- 17215274
TI  - Prospective, multi-centre clinic-based evaluation of four rapid diagnostic tests
      for syphilis.
AB  - OBJECTIVES: To evaluate prospectively four rapid, point-of-care serological tests
      for syphilis in prenatal or high risk populations in four countries. METHODS:
      Tests were performed on consecutive clinic attenders, using whole blood in the
      clinic, and whole blood and serum in the laboratory. The sensitivity and
      specificity of each test was evaluated, using a standard treponemal test
      (Treponema pallidum haemagglutination assay (TPHA) or fluorescent treponemal
      antibody, absorbed (FTA-ABS) as gold standard. Non-treponemal tests (rapid plasma
      reagin (RPR) or venereal diseases research laboratory (VDRL) tests) were also
      performed on all subjects at three sites. RESULTS: The specificity of each rapid
      test was >95% at each site. Sensitivities varied from 64-100% and, in most cases,
      were lower when whole blood was used rather than serum. CONCLUSIONS: Rapid
      serological tests for syphilis are an acceptable alternative to conventional
      laboratory tests. Since they do not require equipment or electricity, they could
      increase coverage of syphilis screening, and enable treatment to be given at the
      first clinic visit.

PMID- 17215275
TI  - Evaluation of a rapid point-of-care test for the detection of gonococcal
      infection among female sex workers in Benin.
AB  - OBJECTIVES: To assess the validity of the PATH (Seattle, Washington, USA) GC
      Check rapid test, a point-of-care immunochromatographic strip test, in the
      detection of gonococcal infection among female sex workers (FSWs) in Benin.
      METHODS: Women consulting consecutively at two FSW-dedicated clinics in Cotonou
      and Porto Novo (Benin) were recruited over three, 1-month periods between October
      2003 and July 2004. After written informed consent, participants were
      administered a short interview and underwent a speculum examination where two
      cervical swabs were collected (in a subset of women, a vaginal swab was also
      collected). One cervical swab and the vaginal swab were immediately tested with
      the rapid test. The other cervical swab was frozen at -20 degrees C for at most
      four weeks and then transported to Quebec (Canada), where it was tested with the
      Roche Amplicor CT/NG PCR assay. Samples positive for gonococcal infection were
      confirmed using a 16SrRNA PCR assay. RESULTS: 1084 FSWs (median age 29 years)
      participated in the study, of whom 50 (4.6%) had a confirmed gonococcal
      infection. The sensitivity, specificity, positive and negative predictive values
      of the rapid test on cervical samples were 70.0% (95% confidence interval (CI)
      55.4% to 82.1%), 97.2% (95% CI 96.0% to 98.1%), 54.7% and 98.5%, respectively.
      The sensitivity of the rapid test on vaginal swabs among 759 women (37 positives
      for gonococcal infection) was significantly lower than with the cervical swab
      (54.1%, p = 0.008), whereas the specificity was comparable (98.2%, p = 0.13).
      CONCLUSIONS: The PATH GC-Check test may be as efficient as a gold standard
      polymerase chain reaction (PCR) test for treating gonococcal infection when
      taking into account the proportion of women who do not return for their test
      results. In clinics serving populations with moderate prevalence of this
      infection, it could significantly reduce over-treatment compared to the syndromic
      approach.

PMID- 17215276
TI  - Modelling the cost-effectiveness of introducing rapid syphilis tests into an
      antenatal syphilis screening programme in Mwanza, Tanzania.
AB  - OBJECTIVES: A study found screening (with rapid plasma reagin (RPR)) pregnant
      women for maternal syphilis was cost-effective in Mwanza, Tanzania. Recently,
      four rapid point-of-care (POC) syphilis tests were evaluated in Mwanza, and found
      to have reasonable sensitivity/specificity. This analysis estimates the relative
      cost-effectiveness of using these POC tests in the Mwanza syphilis screening
      intervention. METHODS: Empirical cost and epidemiological data were used to model
      the potential benefit of using POC tests instead of RPR. Reductions in costs
      relating to training, supplies, and equipment were estimated, and any changes in
      impact due to test sensitivity were included. Additional modelling explored how
      the results vary with prevalence of past infection, misclassified RPR results,
      and if not all women return for treatment. RESULTS: The cost-effectiveness of
      using POC tests is mainly dependent on their cost and sensitivity for high titre
      active syphilis (HTAS). Savings due to reductions in training and equipment are
      small. Current POC tests may save more disability-adjusted life years (DALYs)
      than the RPR test in Mwanza, but the test cost needs to be <0.63 US dollars to be
      as cost-effective as RPR. However, the cost-effectiveness of the RPR test worsens
      by 15% if its HTAS sensitivity had been 75% instead of 86%, and by 25-65% if 20
      40% of women had not returned for treatment. In such settings, POC tests could
      improve cost-effectiveness. Lastly, the cost-effectiveness of POC tests is
      affected little by the prevalence of syphilis, false RPR-positives, and past
      infections. DISCUSSION: Although the price of most POC tests needs to be reduced
      to make them as cost-effective as RPR, their simplicity and limited requirements
      for electricity/equipment suggest their use could improve the coverage of
      antenatal syphilis screening in developing countries.

PMID- 17215277
TI  - The infected cell protein 0 encoded by bovine herpesvirus 1 (bICP0) induces
      degradation of interferon response factor 3 and, consequently, inhibits beta
      interferon promoter activity.
AB  - The ICP0 protein (bICP0) encoded by bovine herpesvirus 1 is the major viral
      regulatory protein because it stimulates all viral promoters and, consequently,
      productive infection. Like other ICP0 analogues encoded by Alphaherpesvirinae
      subfamily members, bICP0 contains a zinc RING finger near its amino terminus that
      is necessary for activating transcription, regulating subcellular localization,
      and inhibiting interferon-dependent transcription. In this study, we discovered
      that sequences near the C terminus, and the zinc RING finger, are necessary for
      inhibiting the human beta interferon (IFN-beta) promoter. In contrast to herpes
      simplex virus type 1-encoded ICP0, bICP0 reduces interferon response factor 3
      (IRF3), but not IRF7, protein levels in transiently transfected cells. The zinc
      RING finger and sequences near the C terminus are necessary for bICP0-induced
      degradation of IRF3. A proteasome inhibitor, lactacystin, interfered with bICP0
      induced degradation of IRF3, suggesting that bICP0, directly or indirectly,
      targets IRF3 for proteasome-dependent degradation. IRF3, but not IRF7, is not
      readily detectable in the nuclei of productively infected bovine cells during the
      late stages of infection. In the context of productive infection, IRF3 and IRF7
      are detected in the nucleus at early times after infection. At late times after
      infection, IRF7, but not IRF3, is still detectable in the nuclei of infected
      cells. Collectively, these studies suggest that the ability of bICP0 to reduce
      IRF3 protein levels is important with respect to disarming the IFN response
      during productive infection.

PMID- 17215278
TI  - Heparan sulfate binding can contribute to the neurovirulence of neuroadapted and
      nonneuroadapted Sindbis viruses.
AB  - Cell culture-adapted laboratory strains of Sindbis virus (SB) exhibit efficient
      initial attachment to cell surface heparan sulfate (HS) receptors. In contrast,
      non-cell-adapted strains, such as the SB consensus sequence virus TR339, interact
      weakly with HS and cell surfaces. Regardless of their HS binding phenotype, most
      SB strains do not cause fatal disease in adult mice, whether inoculated
      subcutaneously (s.c.) or intracranially (i.c.). However, laboratory strains of SB
      can be rendered neurovirulent for adult mice by introduction of a glutamine (Gln)
      to-histidine (His) mutation at position 55 of the E2 envelope glycoprotein. In
      the current work, we have determined that E2 His 55-containing viruses require a
      second-site mutation (Glu to Lys) at E2 position 70 that confers efficient HS
      binding in order to exhibit virulence for adult mice and that virulence is
      correlated with very high infectivity for many cell types. Furthermore,
      introduction of E2 Lys 70 or certain other HS-binding mutations alone also
      increased morbidity and/or mortality over that of TR339 for older mice inoculated
      i.c. However, all viruses containing single HS-binding mutations were attenuated
      in s.c. inoculated suckling mice in comparison with TR339. These results suggest
      that HS binding may attenuate viral disease that is dependent on high-titer
      viremia; however, efficient cell attachment through HS binding can increase
      virulence, presumably through enhancing the replication of SB within specific
      host tissues such as the brain.

PMID- 17215279
TI  - The MyD116 African swine fever virus homologue interacts with the catalytic
      subunit of protein phosphatase 1 and activates its phosphatase activity.
AB  - The DP71L protein of African swine fever virus (ASFV) shares sequence similarity
      with the herpes simplex virus ICP34.5 protein over a C-terminal domain. We showed
      that the catalytic subunit of protein phosphatase 1 (PP1) interacts specifically
      with the ASFV DP71L protein in a yeast two-hybrid screen. The chimeric full
      length DP71L protein, from ASFV strain Badajoz 71 (BA71V), fused to glutathione S
      transferase (DP71L-GST) was expressed in Escherichia coli and shown to bind
      specifically to the PP1-alpha catalytic subunit expressed as a histidine fusion
      protein (6xHis-PP1alpha) in E. coli. The functional effects of this interaction
      were investigated by measuring the levels of PP1 and PP2A in ASFV-infected Vero
      cells. This showed that infection with wild-type ASFV strain BA71V activated PP1
      between two- and threefold over that of mock-infected cells. This activation did
      not occur in cells infected with the BA71V isolate in which the DP71L gene had
      been deleted, suggesting that expression of DP71L leads to PP1 activation. In
      contrast, no effect was observed on the activity of PP2A following ASFV
      infection. We showed that infection of cells with wild-type BA71V virus resulted
      in decreased phosphorylation of the alpha subunit of eukaryotic initiation factor
      2 (eIF-2alpha). ICP34.5 recruits PP1 to dephosphorylate the alpha subunit of
      eukaryotic translational initiation factor 2 (also known as eIF-2alpha); possibly
      the ASFV DP71L protein has a similar function.

PMID- 17215280
TI  - Scavenger receptor BI and BII expression levels modulate hepatitis C virus
      infectivity.
AB  - Hepatitis C virus (HCV) enters cells via a pH- and clathrin-dependent endocytic
      pathway. Scavenger receptor BI (SR-BI) and CD81 are important entry factors for
      HCV internalization into target cells. The SR-BI gene gives rise to at least two
      mRNA splice variants, SR-BI and SR-BII, which differ in their C termini. SR-BI
      internalization remains poorly understood, but SR-BII is reported to endocytose
      via a clathrin-dependent pathway, making it an attractive target for HCV
      internalization. We demonstrate that HCV soluble E2 can interact with human SR-BI
      and SR-BII. Increased expression of SR-BI and SR-BII in the Huh-7.5 hepatoma cell
      line enhanced HCV strain J6/JFH and JFH infectivity, suggesting that endogenous
      levels of these receptors limit infection. Elevated expression of SR-BI, but not
      SR-BII, increased the rate of J6/JFH infection, which may reflect altered
      intracellular trafficking of the splice variants. In human plasma, HCV particles
      have been reported to be complexed with lipoproteins, suggesting an indirect
      interaction of the virus with SR-BI and other lipoprotein receptors. Plasma from
      J6/JFH-infected uPA-SCID mice transplanted with human hepatocytes demonstrates an
      increased infectivity for SR-BI/II-overexpressing Huh-7.5 cells. Plasma-derived
      J6/JFH infectivity was inhibited by an anti-E2 monoclonal antibody, suggesting
      that plasma virus interaction with SR-BI was glycoprotein dependent. Finally,
      anti-SR-BI antibodies inhibited the infectivity of cell culture- and plasma
      derived J6/JFH, suggesting a critical role for SR-BI/II in HCV infection.

PMID- 17215281
TI  - Role of interferon regulatory factor 3 in type I interferon responses in
      rotavirus-infected dendritic cells and fibroblasts.
AB  - The main pathway for the induction of type I interferons (IFN) by viruses is
      through the recognition of viral RNA by cytosolic receptors and the subsequent
      activation of interferon regulatory factor 3 (IRF-3), which drives IFN-alpha/beta
      transcription. In addition to their role in inducing an antiviral state, type I
      IFN also play a role in modulating adaptive immune responses, in part via their
      effects on dendritic cells (DCs). Many viruses have evolved mechanisms to
      interfere with type I IFN induction, and one recently reported strategy for
      achieving this is by targeting IRF-3 for degradation, as shown for rotavirus
      nonstructural protein 1 (NSP1). It was therefore of interest to investigate
      whether rotavirus-exposed DCs would produce type I IFN and/or mature in response
      to the virus. Our results demonstrate that IRF-3 was rapidly degraded in
      rotavirus-infected mouse embryonic fibroblasts (MEFs) and type I IFN was not
      detected in these cultures. In contrast, rotavirus induced type I IFN production
      in myeloid DCs (mDCs), resulting in their activation. Type I IFN induction in
      response to rotavirus was reduced in mDCs from IRF-3(-/-) mice, indicating that
      IRF-3 was important for mediating the response. Exposure of mDCs to UV-treated
      rotavirus induced significantly higher type I IFN levels, suggesting that
      rotavirus-encoded functions also antagonized the response in DCs. However, in
      contrast to MEFs, this action was not sufficient to completely abrogate type I
      IFN induction, consistent with a role for DCs as sentinels for virus infection.

PMID- 17215282
TI  - AMPK-mediated inhibition of mTOR kinase is circumvented during immediate-early
      times of human cytomegalovirus infection.
AB  - Human cytomegalovirus (HCMV) infection increases synthetic rates in infected
      cells. The resulting increase in energy utilization could potentially increase
      the AMP:ATP ratio, causing activation of 5'-AMP-activated protein kinase (AMPK).
      Activated AMPK promotes inhibition of mammalian target of rapamycin (mTOR)
      kinase, which could be deleterious to the viral infection. Using the AMPK
      activating drug 5-amino-4-imidazolecarboxamide ribose (AICAR), we showed that, by
      12 h post-HCMV infection, inhibition of mTOR by AMPK is circumvented. However,
      growth curves showed that progeny virion production is inhibited when AICAR is
      added, suggesting other inhibitory effects of AICAR or activated AMPK.

PMID- 17215283
TI  - Construction of an infectious rhesus rhadinovirus bacterial artificial chromosome
      for the analysis of Kaposi's sarcoma-associated herpesvirus-related disease
      development.
AB  - Rhesus rhadinovirus (RRV) is closely related to Kaposi's sarcoma-associated
      herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) and causes KSHV-like diseases in
      immunocompromised rhesus macaques (RM) that resemble KSHV-associated diseases
      including multicentric Castleman's disease and non-Hodgkin's lymphoma. RRV
      retains a majority of open reading frames (ORFs) postulated to be involved in the
      pathogenesis of KSHV and is the closest available animal model to KSHV infection
      in humans. Here we describe the generation of a recombinant clone of RRV strain
      17577 (RRV(17577)) utilizing bacterial artificial chromosome (BAC) technology.
      Characterization of the RRV BAC demonstrated that it is a pathogenic molecular
      clone of RRV(17577), producing virus that behaves like wild-type RRV both in
      vitro and in vivo. Specifically, BAC-derived RRV displays wild-type growth
      properties in vitro and readily infects simian immunodeficiency virus-infected
      RM, inducing B cell hyperplasia, persistent lymphadenopathy, and persistent
      infection in these animals. This RRV BAC will allow for rapid genetic
      manipulation of the RRV genome, facilitating the creation of recombinant versions
      of RRV that harbor specific alterations and/or deletions of viral ORFs. This
      system will provide insights into the roles of specific RRV genes in various
      aspects of the viral life cycle and the RRV-associated pathogenesis in vivo in an
      RM model of infection. Furthermore, the generation of chimeric versions of RRV
      containing KSHV genes will allow analysis of the function and contributions of
      KSHV genes to viral pathogenesis by using a relevant primate model system.

PMID- 17215284
TI  - Binding patterns of human norovirus-like particles to buccal and intestinal
      tissues of gnotobiotic pigs in relation to A/H histo-blood group antigen
      expression.
AB  - Histo-blood group antigen (HBGA) phenotypes have been associated with
      susceptibility to human noroviruses (HuNoVs). Our aims were: (i) to determine the
      patterns of A/H HBGA expression in buccal and intestinal tissues of gnotobiotic
      (Gn) pigs; (ii) to determine if virus-like particles (VLPs) of HuNoV genogroup I
      (GI) and GII bind to A- or H-type tissues; (iii) to compare A/H expression and
      VLP binding patterns and confirm their binding specificities by blocking assays;
      (iv) to develop a hemagglutination inhibition test using buccal cells from live
      pigs to determine the Gn pig's A/H phenotype and to match viral strains with
      previously determined HuNoV VLP binding specificities; and (v) to determine the
      A/H phenotypes and compare these data to the infection outcomes of a previous
      study of 65 Gn pigs inoculated with HuNoV GII/4 strain HS66 and expressing A
      and/or H or neither antigen on their buccal and intestinal tissues (S. Cheetham,
      M. Souza, T. Meulia, S. Grimes, M. G. Han, and L. J. Saif, J. Virol. 80:10372
      10381, 2006). We found that the HuNoV GI/GII VLPs of different clusters bound to
      tissues from four pigs tested (two A+ and two H+). The GI/1 and GII/4 VLPs bound
      extensively to duodenal and buccal tissues from either A+ or H+ pigs, but
      surprisingly, GII/1 and GII/3 VLPs bound minimally to the duodenum of an A+ pig.
      The VLP binding was partially inhibited by A-, H1-, or H2-specific monoclonal
      antibodies, but was completely blocked by porcine mucin. Comparing the A/H
      phenotypes of 65 HS66-inoculated Gn pigs from our previous study, we found that
      significantly more A+ and H(+) pigs (51%) than non-A+ and non-H+ pigs (12.5%)
      shed virus. From the 22 convalescent pigs, significantly more A+ or H+ pigs (66%)
      than non-A+ or H+ pigs (25%) seroconverted.

PMID- 17215285
TI  - Bovine viral diarrhea virus: prevention of persistent fetal infection by a
      combination of two mutations affecting Erns RNase and Npro protease.
AB  - Different genetically engineered mutants of bovine viral diarrhea virus (BVDV)
      were analyzed for the ability to establish infection in the fetuses of pregnant
      heifers. The virus mutants exhibited either a deletion of the overwhelming part
      of the genomic region coding for the N-terminal protease N(pro), a deletion of
      codon 349, which abrogates the RNase activity of the structural glycoprotein
      E(rns), or a combination of both mutations. Two months after infection of
      pregnant cattle with wild-type virus or either of the single mutants, the
      majority of the fetuses contained virus or were aborted or found dead in the
      uterus. In contrast, the double mutant was not recovered from fetal tissues after
      a similar challenge, and no dead fetuses were found. This result was verified
      with a nonrelated BVDV containing similar mutations. After intrauterine challenge
      with wild-type virus, mutated viruses, and cytopathogenic BVDV, all viruses could
      be detected in fetal tissue after 5, 7, and 14 days. Type 1 interferon (IFN)
      could be detected in fetal serum after challenge, except with wild-type
      noncytopathogenic BVDV. On days 7 and 14 after challenge, the largest quantities
      of IFN in fetal serum were induced by the N(pro) and RNase-negative double mutant
      virus. The longer duration of fetal infection with the double mutant resulted in
      abortion. Therefore, for the first time, we have demonstrated the essential role
      of both N(pro) and E(rns) RNase in blocking interferon induction and establishing
      persistent infection by a pestivirus in the natural host.

PMID- 17215287
TI  - Phosphoacceptor site S173 in the regulatory domain of Epstein-Barr Virus ZEBRA
      protein is required for lytic DNA replication but not for activation of viral
      early genes.
AB  - The Epstein-Barr virus ZEBRA protein controls the viral lytic cycle. ZEBRA
      activates the transcription of viral genes required for replication. ZEBRA also
      binds to oriLyt and interacts with components of the viral replication machinery.
      The mechanism that differentiates the roles of ZEBRA in regulation of
      transcription and initiation of lytic replication is unknown. Here we show that
      S173, a residue in the regulatory domain, is obligatory for ZEBRA to function as
      an origin binding protein but is dispensable for its role as a transcriptional
      activator of early genes. Serine-to-alanine substitution of this residue, which
      prevents phosphorylation of S173, resulted in a threefold reduction in the DNA
      binding affinity of ZEBRA for oriLyt, as assessed by chromatin
      immunoprecipitation. An independent assay based on ZEBRA solubility demonstrated
      a marked defect in DNA binding by the Z(S173A) mutant. The phenotype of a
      phosphomimetic mutant, the Z(S173D) mutant, was similar to that of wild-type
      ZEBRA. Our findings suggest that phosphorylation of S173 promotes viral
      replication by enhancing ZEBRA's affinity for DNA. The results imply that
      stronger DNA binding is required for ZEBRA to activate replication than that
      required to activate transcription.

PMID- 17215286
TI  - Classical swine fever virus Npro interacts with interferon regulatory factor 3
      and induces its proteasomal degradation.
AB  - Viruses have evolved a multitude of strategies to subvert the innate immune
      system by interfering with components of the alpha/beta interferon (IFN
      alpha/beta) induction and signaling pathway. It is well established that the
      pestiviruses prevent IFN-alpha/beta induction in their primary target cells, such
      as epitheloidal and endothelial cells, macrophages, and conventional dendritic
      cells, a phenotype mediated by the viral protein N(pro). Central players in the
      IFN-alpha/beta induction cascade are interferon regulatory factor 3 (IRF3) and
      IRF7. Recently, it was proposed that classical swine fever virus (CSFV), the
      porcine pestivirus, induced the loss of IRF3 by inhibiting the transcription of
      IRF3 mRNA. In the present study, we show that endogenous IRF3 and IRF3 expressed
      from a cytomegalovirus (CMV) promoter are depleted in the presence of CSFV by
      means of N(pro), while CSFV does not inhibit CMV promoter-driven protein
      expression. We also demonstrate that CSFV does not reduce the transcriptional
      activity of the IRF3 promoter and does not affect the stability of IRF3 mRNA. In
      fact, CSFV N(pro) induces proteasomal degradation of IRF3, as demonstrated by
      proteasome inhibition studies. Furthermore, N(pro) coprecipitates with IRF3,
      suggesting that the proteasomal degradation of IRF3 is induced by a direct or
      indirect interaction with N(pro). Finally, we show that N(pro) does not
      downregulate IRF7 expression.

PMID- 17215288
TI  - Importance of the anti-interferon capacity of Sendai virus C protein for
      pathogenicity in mice.
AB  - The Sendai virus (SeV) C protein blocks signal transduction of interferon (IFN),
      thereby counteracting the antiviral actions of IFN. Using HeLa cell lines
      expressing truncated or mutated SeV C proteins, we found that the C-terminal half
      has anti-IFN capacity, and that K(151)A, E(153)A, and R(154)A substitutions in
      the C protein eliminated this capacity. Here, we further created the mutant virus
      SeV Cm*, in which K(151)A, E(153)K, and R(157)L substitutions in the C protein
      were introduced without changing the amino acid sequence of overlapped P, V, and
      W proteins. SeV Cm* was found to lack anti-IFN capacity, as expected. While the
      growth rate and final yield of SeV Cm* were inferior to those of the wild-type
      SeV in IFN-responsive, STAT1-positive 2fTGH cells, SeV Cm* grew equivalently to
      the wild-type SeV in IFN-nonresponsive, STAT1-deficient U3A cells. SeV Cm* was
      thus shown to maintain multiplication capacity, except that it lacked anti-IFN
      capacity. Intranasally inoculated SeV Cm* could propagate in the lungs of STAT1(
      /-) mice but was cleared from those of STAT1(+/+) mice without propagation. It
      was found that the anti-IFN capacity of the SeV C protein was indispensable for
      pathogenicity in mice. Conversely, the results show that the innate immunity
      contributed to elimination of SeV in early stages of infection in the absence of
      anti-IFN capacity.

PMID- 17215289
TI  - In vitro study of the effects of precore and lamivudine-resistant mutations on
      hepatitis B virus replication.
AB  - Understanding the consequences of mutation in the hepatitis B virus (HBV) genome
      on HBV replication is critical for treating chronic HBV infection. In this study,
      HBV replication in HepG2 cells initiated by transduction with precore (PC),
      rtM204I, and wild-type (wt) HBV recombinant baculoviruses was compared. The
      pattern and magnitude of HBV replication initiated by the PC HBV recombinant
      baculovirus were similar to those observed for wt HBV throughout the time course
      examined. In contrast, when the rtM204I mutation was introduced into wt HBV, by
      day 10 postinfection the levels of intra- and extracellular HBV DNA were markedly
      reduced compared to those for wt HBV. Although the rtM204I mutation reduced the
      production of HBV replicative intermediates, no effect on the level of covalently
      closed circular DNA or HBV transcripts was observed at late time points.
      Coinfection studies with different ratios of wt and rtM204I baculoviruses showed
      that the rtM204I variant did not produce a product that inhibited HBV
      replication. However, the combination of the wt and rtM204I baculoviruses yielded
      HBV DNA levels at late time points that were greater than those for the wt alone,
      suggesting that wt polymerase may function in trans to boost rtM204I replication.
      We concluded that the rtM204I mutation generates a polymerase that is not only
      resistant to lamivudine but also replicates nucleic acids to lower levels in
      vitro.

PMID- 17215290
TI  - Direct visualization of the putative portal in the Kaposi's sarcoma-associated
      herpesvirus capsid by cryoelectron tomography.
AB  - Genetic and biochemical studies have suggested the existence of a bacteriophage
      like, DNA-packaging/ejecting portal complex in herpesviruses capsids, but its
      arrangement remained unknown. Here, we report the first visualization of a unique
      vertex in the Kaposi's sarcoma-associated herpesvirus (KSHV) capsid by
      cryoelectron tomography, thus providing direct structural evidence for the
      existence of a portal complex in a gammaherpesvirus. This putative KSHV portal is
      an internally localized, umbilicated structure and lacks all of the external
      machineries characteristic of portals in DNA bacteriophages.

PMID- 17215291
TI  - UL20 protein functions precede and are required for the UL11 functions of herpes
      simplex virus type 1 cytoplasmic virion envelopment.
AB  - Egress of herpes simplex virus type 1 (HSV-1) from the nucleus of the infected
      cell to extracellular spaces involves a number of distinct steps, including
      primary envelopment by budding into the perinuclear space, de-envelopment into
      the cytoplasm, cytoplasmic reenvelopment, and translocation of enveloped virions
      to extracellular spaces. UL20/gK-null viruses are blocked in cytoplasmic virion
      envelopment and egress, as indicated by an accumulation of unenveloped or
      partially enveloped capsids in the cytoplasm. Similarly, UL11-null mutants
      accumulate unenveloped capsids in the cytoplasm. To assess whether UL11 and
      UL20/gK function independently or synergistically in cytoplasmic envelopment,
      recombinant viruses having either the UL20 or UL11 gene deleted were generated.
      In addition, a recombinant virus containing a deletion of both UL20 and UL11
      genes was constructed using the HSV-1(F) genome cloned into a bacterial
      artificial chromosome. Ultrastructural examination of virus-infected cells showed
      that both UL20- and UL11-null viruses accumulated unenveloped capsids in the
      cytoplasm. However, the morphology and distribution of the accumulated capsids
      appeared to be distinct, with the UL11-null virions forming aggregates of capsids
      having diffuse tegument-derived material and the UL20-null virus producing
      individual capsids in close juxtaposition to cytoplasmic membranes. The UL20/UL11
      double-null virions appeared morphologically similar to the UL20-null viruses.
      Experiments on the kinetics of viral replication revealed that the UL20/UL11
      double-null virus replicated in a manner similar to the UL20-null virus.
      Additional experiments revealed that transiently expressed UL11 localized to the
      trans-Golgi network (TGN) independently of either gK or UL20. Furthermore, virus
      infection with the UL11/UL20 double-null virus did not alter the TGN localization
      of transiently expressed UL11 or UL20 proteins, indicating that these proteins
      did not interact. Taken together, these results show that the intracellular
      transport and TGN localization of UL11 is independent of UL20/gK functions, and
      that UL20/gK are required and function prior to UL11 protein in virion
      cytoplasmic envelopment.

PMID- 17215292
TI  - p53-independent endoplasmic reticulum stress-mediated cytotoxicity of a Newcastle
      disease virus strain in tumor cell lines.
AB  - While Newcastle disease virus (NDV) causes serious infections in birds, it is
      apparently nonpathogenic in mammalian species, including humans. Previous
      observations and small-scale clinical trials indicated that NDV exerts oncolytic
      effects. Isolates of NDV were found to have selective affinity to transformed
      cells. We previously showed that the attenuated NDV strain MTH-68/H causes
      apoptotic cell death in cultures of PC12 rat pheochromocytoma cells. The aim of
      the present study was to extend MTH-68/H cytotoxicity testing with human tumor
      cell lines and to analyze certain biochemical aspects of its oncolytic effect.
      MTH-68/H was found to be able to kill a wide range of transformed cells by
      apoptosis. While caspase-8 and caspase-9 are not involved in MTH-68/H-induced
      apoptosis, activation of caspase-3 and caspase-12 was detected in virus-infected
      PC12 cells. A human glioblastoma cell line with repressible expression of the p53
      protein did not show any difference in MTH-68/H sensitivity in its p53-expressing
      and p53-depleted states, indicating that the apoptotic process induced by MTH
      68/H does not depend on p53. Apoptosis was accompanied by virus replication in
      two tumor cell lines tested (PC12 cells and HeLa human cervical cells), and signs
      of endoplasmic reticulum stress (phosphorylation of protein kinase R-like
      endoplasmic reticulum kinase and eIF2alpha) were also detected in transformed
      cells. In contrast, proliferation of nontransformed mouse and rat fibroblast cell
      lines and human primary fibroblasts was not affected by MTH-68/H treatment. MTH
      68/H thus selectively kills tumor cell cultures by inducing endoplasmic reticulum
      stress leading to p53-independent apoptotic cell death.

PMID- 17215293
TI  - Electron tomography of nascent herpes simplex virus virions.
AB  - Cells infected with herpes simplex virus type 1 (HSV-1) were conventionally
      embedded or freeze substituted after high-pressure freezing and stained with
      uranyl acetate. Electron tomograms of capsids attached to or undergoing
      envelopment at the inner nuclear membrane (INM), capsids within cytoplasmic
      vesicles near the nuclear membrane, and extracellular virions revealed the
      following phenomena. (i) Nucleocapsids undergoing envelopment at the INM, or B
      capsids abutting the INM, were connected to thickened patches of the INM by
      fibers 8 to 19 nm in length and < or =5 nm in width. The fibers contacted both
      fivefold symmetrical vertices (pentons) and sixfold symmetrical faces (hexons) of
      the nucleocapsid, although relative to the respective frequencies of these
      subunits in the capsid, fibers engaged pentons more frequently than hexons. (ii)
      Fibers of similar dimensions bridged the virion envelope and surface of the
      nucleocapsid in perinuclear virions. (iii) The tegument of perinuclear virions
      was considerably less dense than that of extracellular virions; connecting fibers
      were observed in the former case but not in the latter. (iv) The prominent
      external spikes emanating from the envelope of extracellular virions were absent
      from perinuclear virions. (v) The virion envelope of perinuclear virions appeared
      denser and thicker than that of extracellular virions. (vi) Vesicles near, but
      apparently distinct from, the nuclear membrane in single sections were derived
      from extensions of the perinuclear space as seen in the electron tomograms. These
      observations suggest very different mechanisms of tegumentation and envelopment
      in extracellular compared with perinuclear virions and are consistent with
      application of the final tegument to unenveloped nucleocapsids in a
      compartment(s) distinct from the perinuclear space.

PMID- 17215294
TI  - Nuclease activity of the MutS homologue MutS2 from Thermus thermophilus is
      confined to the Smr domain.
AB  - MutS homologues are highly conserved enzymes engaged in DNA mismatch repair
      (MMR), meiotic recombination and other DNA modifications. Genome sequencing
      projects have revealed that bacteria and plants possess a MutS homologue, MutS2.
      MutS2 lacks the mismatch-recognition domain of MutS, but contains an extra C
      terminal region called the small MutS-related (Smr) domain. Sequences homologous
      to the Smr domain are annotated as 'proteins of unknown function' in various
      organisms ranging from bacteria to human. Although recent in vivo studies
      indicate that MutS2 plays an important role in recombinational events, there had
      been only limited characterization of the biochemical function of MutS2 and the
      Smr domain. We previously established that Thermus thermophilus MutS2 (ttMutS2)
      possesses endonuclease activity. In this study, we report that a Smr-deleted
      ttMutS2 mutant retains the dimerization, ATPase and DNA-binding activities, but
      has no endonuclease activity. Furthermore, the Smr domain alone was stable and
      functional in binding and incising DNA. It is noteworthy that an endonuclease
      activity is associated with a MutS homologue, which is generally thought to
      recognize specific DNA structures.

PMID- 17215295
TI  - Tfb5 interacts with Tfb2 and facilitates nucleotide excision repair in yeast.
AB  - TFIIH is indispensable for nucleotide excision repair (NER) and RNA polymerase II
      transcription. Its tenth subunit was recently discovered in yeast as Tfb5. Unlike
      other TFIIH subunits, Tfb5 is not essential for cell survival. We have analyzed
      the role of Tfb5 in NER. NER was deficient in the tfb5 deletion mutant cell
      extracts, and was specifically complemented by purified Tfb5 protein. In contrast
      to the extreme ultraviolet (UV) sensitivity of rad14 mutant cells that lack any
      NER activity, tfb5 deletion mutant cells were moderately sensitive to UV
      radiation, resembling that of the tfb1-101 mutant cells in which TFIIH activity
      is compromised but not eliminated. Thus, Tfb5 protein directly participates in
      NER and is an accessory NER protein that stimulates the repair to the proficient
      level. Lacking a DNA binding activity, Tfb5 was found to interact with the core
      TFIIH subunit Tfb2, but not with other NER proteins. The Tfb5-Tfb2 interaction
      was correlated with the cellular NER function of Tfb5, supporting the functional
      importance of this interaction. Our results led to a model in which Tfb5 acts as
      an architectural stabilizer conferring structural rigidity to the core TFIIH such
      that the complex is maintained in its functional architecture.

PMID- 17215296
TI  - The zebrafish zic2a-zic5 gene pair acts downstream of canonical Wnt signaling to
      control cell proliferation in the developing tectum.
AB  - Wnt growth factors acting through the canonical intracellular signaling cascade
      play fundamental roles during vertebrate brain development. In particular,
      canonical Wnt signaling is crucial for normal development of the dorsal midbrain,
      the future optic tectum. Wnts act both as patterning signals and as regulators of
      cell growth. In the developing tectum, Wnt signaling is mitogenic; however, the
      mechanism of Wnt function is not known. As a step towards better understanding
      this mechanism, we have identified two new Wnt targets, the closely linked zic2a
      and zic5 genes. Using a combination of in vivo assays, we show that zic2a and
      zic5 transcription is activated by Tcf/Lef transcription factors in the dorsal
      midbrain. Zic2a and Zic5, in turn, have essential, cooperative roles in promoting
      cell proliferation in the tectum, but lack obvious patterning functions.
      Collectively these findings suggest that Wnts control midbrain proliferation, at
      least in part, through regulation of two novel target genes, the zic2a-zic5 gene
      pair.

PMID- 17215297
TI  - Auxin-dependent regulation of lateral root positioning in the basal meristem of
      Arabidopsis.
AB  - In plants, the developmental mechanisms that regulate the positioning of lateral
      organs along the primary root are currently unknown. We present evidence on how
      lateral root initiation is controlled in a spatiotemporal manner in the model
      plant Arabidopsis thaliana. First, lateral roots are spaced along the main axis
      in a regular left-right alternating pattern that correlates with gravity-induced
      waving and depends on AUX1, an auxin influx carrier essential for gravitropic
      response. Second, we found evidence that the priming of pericycle cells for
      lateral root initiation might take place in the basal meristem, correlating with
      elevated auxin sensitivity in this part of the root. This local auxin
      responsiveness oscillates with peaks of expression at regular intervals of 15
      hours. Each peak in the auxin-reporter maximum correlates with the formation of a
      consecutive lateral root. Third, auxin signaling in the basal meristem triggers
      pericycle cells for lateral root initiation prior to the action of INDOLE-3
      ACETIC ACID14 (SOLITARY ROOT).

PMID- 17215298
TI  - How is pluripotency determined and maintained?
AB  - Mouse embryonic stem (ES) cells are pluripotent, as they have the ability to
      differentiate into the various cell types of a vertebrate embryo. Pluripotency is
      a property of the inner cell mass (ICM), from which mouse ES cells are derived,
      and of the epiblast of the blastocyst. Recent extensive molecular studies of
      mouse ES cells have revealed the unique molecular mechanisms that govern
      pluripotency. These studies show that ES cells continue to self-renew because of
      a self-organizing network of transcription factors that prevents their
      differentiation and promotes their proliferation, and because of epigenetic
      processes that might be under the control of the pluripotent transcription factor
      network.

PMID- 17215299
TI  - Dorsal-ventral midline signaling in the developing Drosophila eye.
AB  - Boundaries between different cell types play key roles in many developmental
      patterning processes. They can be established by various mechanisms, and
      signaling between the different cell types can occur in a number of ways. One
      mechanism of crossboundary signaling is controlled by the Notch (N)-modifying
      protein Fringe (Fng). At the Drosophila wing dorsal-ventral (D-V) border, the
      mechanism by which an Fng(+)-Fng(-) interface controls local N activation has
      been well characterized. A similar N-activating Fng(+)-Fng(-) interface has also
      been described at the D-V border of the fly eye, but the mechanisms that
      establish and regulate it are different from those in the wing. Here we describe
      the ventral role of the Sloppy-paired (Slp) transcription factor, and its
      interactions with dorsally expressed Iroquois (Iro) transcription factors in the
      regulation of signaling about the Fng(+)-Fng(-) interface in the developing eye.
      The two transcription factors are mutually repressive and initially abut at the D
      V midline. However, N signaling at the interface downregulates Slp expression,
      and a gap opens between the two expression domains in which Serrate (Ser, an N
      ligand) is upregulated.

PMID- 17215300
TI  - MRG-1, an autosome-associated protein, silences X-linked genes and protects
      germline immortality in Caenorhabditis elegans.
AB  - MRG15, a mammalian protein related to the mortality factor MORF4, is required for
      cell proliferation and embryo survival. Our genetic analysis has revealed that
      the Caenorhabditis elegans ortholog MRG-1 serves similar roles. Maternal MRG-1
      promotes embryo survival and is required for proliferation and immortality of the
      primordial germ cells (PGCs). As expected of a chromodomain protein, MRG-1
      associates with chromatin. Unexpectedly, it is concentrated on the autosomes and
      not detectable on the X chromosomes. This association is not dependent on the
      autosome-enriched protein MES-4. Focusing on possible roles of MRG-1 in
      regulating gene expression, we determined that MRG-1 is required to maintain
      repression in the maternal germ line of transgenes on extrachromosomal arrays,
      and of several X-linked genes previously shown to depend on MES-4 for repression.
      MRG-1 is not required for PGCs to acquire transcriptional competence or for the
      turn-on of expression of several PGC-expressed genes (pgl-1, glh-1, glh-4 and nos
      1). By contrast to this result in PGCs, MRG-1 is required for ectopic expression
      of those germline genes in somatic cells lacking the NuRD complex component MEP
      1. We discuss how an autosome-enriched protein might repress genes on the X
      chromosome, promote PGC proliferation and survival, and influence the germ versus
      soma distinction.

PMID- 17215301
TI  - C. elegans EVI1 proto-oncogene, EGL-43, is necessary for Notch-mediated cell fate
      specification and regulates cell invasion.
AB  - During C. elegans development, LIN-12 (Notch) signaling specifies the anchor cell
      (AC) and ventral uterine precursor cell (VU) fates from two equivalent pre-AC/pre
      VU cells in the hermaphrodite gonad. Once specified, the AC induces patterned
      proliferation of vulva via expression of LIN-3 (EGF) and then invades into the
      vulval epithelium. Although these cellular processes are essential for the proper
      organogenesis of vulva and appear to be temporally regulated, the mechanisms that
      coordinate the processes are not well understood. We computationally identified
      egl-43 as a gene likely to be expressed in the pre-AC/pre-VU cells and the AC,
      based on the presence of an enhancer element similar to the one that transcribes
      lin-3 in the same cells. Genetic epistasis analyses reveal that egl-43 acts
      downstream of or parallel to lin-12 in AC/VU cell fate specification at an early
      developmental stage, and functions downstream of fos-1 as well as upstream of zmp
      1 and him-4 to regulate AC invasion at a later developmental stage.
      Characterization of the egl-43 regulatory region suggests that EGL-43 is a direct
      target of LIN-12 and HLH-2 (E12/47), which is required for the specification of
      the VU fate during AC/VU specification. EGL-43 also regulates basement membrane
      breakdown during AC invasion through a FOS-1-responsive regulatory element that
      drives EGL-43 expression in the AC and VU cells at the later stage. Thus, egl-43
      integrates temporally distinct upstream regulatory events and helps program cell
      fate specification and cell invasion.

PMID- 17215302
TI  - SEL-2, the C. elegans neurobeachin/LRBA homolog, is a negative regulator of lin
      12/Notch activity and affects endosomal traffic in polarized epithelial cells.
AB  - The vulval precursor cells (VPCs) of Caenorhabditis elegans are polarized
      epithelial cells that adopt a precise pattern of fates through regulated activity
      of basolateral LET-23/EGF receptor and apical LIN-12/Notch. During VPC
      patterning, there is reciprocal modulation of endocytosis and trafficking of both
      LET-23 and LIN-12. We identified sel-2 as a negative regulator of lin-12/Notch
      activity in the VPCs, and found that SEL-2 is the homolog of two closely related
      human proteins, neurobeachin (also known as BCL8B) and LPS-responsive, beige-like
      anchor protein (LRBA). SEL-2, neurobeachin and LRBA belong to a distinct
      subfamily of BEACH-WD40 domain-containing proteins. Loss of sel-2 activity leads
      to basolateral mislocalization and increased accumulation of LIN-12 in VPCs in
      which LET-23 is not active, and to impaired downregulation of basolateral LET-23
      in VPCs in which LIN-12 is active. Downregulation of apical LIN-12 in the VPC in
      which LET-23 is active is not affected. In addition, in sel-2 mutants, the
      polarized cells of the intestinal epithelium display an aberrant accumulation of
      the lipophilic dye FM4-64 when the dye is presented to the basolateral surface.
      Our observations indicate that SEL-2/neurobeachin/LRBA is involved in endosomal
      traffic and may be involved in efficient delivery of cell surface proteins to the
      lysosome. Our results also suggest that sel-2 activity may contribute to the
      appropriate steady-state level of LIN-12 or to trafficking events that affect
      receptor activation.

PMID- 17215303
TI  - The Ovhts polyprotein is cleaved to produce fusome and ring canal proteins
      required for Drosophila oogenesis.
AB  - An essential component of normal development is controlling the transition from
      cell proliferation to differentiation. One such transition occurs during
      Drosophila oogenesis. In early oogenesis, germ cells undergo mitotic
      proliferation and contain a specialized organelle called a fusome, whereas later
      post-mitotic cells differentiate and lose the fusome as F-actin-rich ring canals
      form. The hts gene encodes the only Drosophila Adducin, and is a female-sterile
      mutant that affects both the fusome and ring canals. We show that one Hts
      protein, Ovhts, is a polyprotein that is cleaved to produce two products, Ovhts
      Fus and Ovhts-RC. Whereas Ovhts-Fus localizes to the fusome in mitotic cells,
      Ovhts-RC localizes to ring canals throughout later oogenesis. We demonstrate that
      an uncleavable version of Ovhts delays the transition from fusome-containing
      cells to those that have ring canals. Ovhts is the first polyprotein shown to
      produce proteins that function in separate structures.

PMID- 17215304
TI  - Fibroblast growth factor receptor 2 tyrosine kinase is required for prostatic
      morphogenesis and the acquisition of strict androgen dependency for adult tissue
      homeostasis.
AB  - The fibroblast growth factor (FGF) family consists of 22 members and regulates a
      broad spectrum of biological activities by activating diverse isotypes of FGF
      receptor tyrosine kinases (FGFRs). Among the FGFs, FGF7 and FGF10 have been
      implicated in the regulation of prostate development and prostate tissue
      homeostasis by signaling through the FGFR2 isoform. Using conditional gene
      ablation with the Cre-LoxP system in mice, we demonstrate a tissue-specific
      requirement for FGFR2 in urogenital epithelial cells--the precursors of prostatic
      epithelial cells--for prostatic branching morphogenesis and prostatic growth.
      Most Fgfr2 conditional null (Fgfr2(cn)) embryos developed only two dorsal
      prostatic (dp) and two lateral prostatic (lp) lobes. This contrasts to wild-type
      prostate, which has two anterior prostatic (ap), two dp, two lp and two ventral
      prostatic (vp) lobes. Unlike wild-type prostates, which are composed of well
      developed epithelial ductal networks, the Fgfr2(cn) prostates, despite retaining
      a compartmented tissue structure, exhibited a primitive epithelial architecture.
      Moreover, although Fgfr2(cn) prostates continued to produce secretory proteins in
      an androgen-dependent manner, they responded poorly to androgen with respect to
      tissue homeostasis. The results demonstrate that FGFR2 is important for prostate
      organogenesis and for the prostate to develop into a strictly androgen-dependent
      organ with respect to tissue homeostasis but not to the secretory function,
      implying that androgens may regulate tissue homeostasis and tissue function
      differently. Therefore, Fgfr2(cn) prostates provide a useful animal model for
      scrutinizing molecular mechanisms by which androgens regulate prostate growth,
      homeostasis and function, and may yield clues as to how advanced-tumor prostate
      cells escape strict androgen regulations.

PMID- 17215305
TI  - Distinct functions of alpha-Spectrin and beta-Spectrin during axonal pathfinding.
AB  - Cell-shape changes during development require a precise coupling of the
      cytoskeleton with proteins situated in the plasma membrane. Important elements
      controlling the shape of cells are the Spectrin proteins that are expressed as a
      subcortical cytoskeletal meshwork linking specific membrane receptors with F
      actin fibers. Here, we demonstrate that Drosophila karussell mutations affect
      beta-spectrin and lead to distinct axonal patterning defects in the embryonic
      CNS. karussell mutants display a slit-sensitive axonal phenotype characterized by
      axonal looping in stage-13 embryos. Further analyses of individual, labeled
      neuroblast lineages revealed abnormally structured growth cones in these animals.
      Cell-type-specific rescue experiments demonstrate that beta-Spectrin is required
      autonomously and non-autonomously in cortical neurons to allow normal axonal
      patterning. Within the cell, beta-Spectrin is associated with alpha-Spectrin. We
      show that expression of the two genes is tightly regulated by post-translational
      mechanisms. Loss of beta-Spectrin significantly reduces levels of neuronal alpha
      Spectrin expression, whereas gain of beta-Spectrin leads to an increase in alpha
      Spectrin protein expression. Because the loss of alpha-spectrin does not result
      in an embryonic nervous system phenotype, beta-Spectrin appears to act at least
      partially independent of alpha-Spectrin to control axonal patterning.

PMID- 17215307
TI  - Mammalian Polycomb Scmh1 mediates exclusion of Polycomb complexes from the XY
      body in the pachytene spermatocytes.
AB  - The product of the Scmh1 gene, a mammalian homolog of Drosophila Sex comb on
      midleg, is a constituent of the mammalian Polycomb repressive complexes 1 (Prc1).
      We have identified Scmh1 as an indispensable component of the Prc1. During
      progression through pachytene, Scmh1 was shown to be excluded from the XY body at
      late pachytene, together with other Prc1 components such as Phc1, Phc2, Rnf110
      (Pcgf2), Bmi1 and Cbx2. We have identified the role of Scmh1 in mediating the
      survival of late pachytene spermatocytes. Apoptotic elimination of Scmh1(-/-)
      spermatocytes is accompanied by the preceding failure of several specific
      chromatin modifications at the XY body, whereas synapsis of homologous autosomes
      is not affected. It is therefore suggested that Scmh1 is involved in regulating
      the sequential changes in chromatin modifications at the XY chromatin domain of
      the pachytene spermatocytes. Restoration of defects in Scmh1(-/-) spermatocytes
      by Phc2 mutation indicates that Scmh1 exerts its molecular functions via its
      interaction with Prc1. Therefore, for the first time, we are able to indicate a
      functional involvement of Prc1 during the meiotic prophase of male germ cells and
      a regulatory role of Scmh1 for Prc1, which involves sex chromosomes.

PMID- 17215306
TI  - Mapping the consequence of Notch1 proteolysis in vivo with NIP-CRE.
AB  - The four highly conserved Notch receptors receive short-range signals that
      control many biological processes during development and in adult vertebrate
      tissues. The involvement of Notch1 signaling in tissue self-renewal is less
      clear, however. We developed a novel genetic approach N(1)IP-CRE (Notch1
      Intramembrane Proteolysis) to follow, at high resolution, the descendents of
      cells experiencing Notch1 activation in the mouse. By combining N(1)IP-CRE with
      loss-of-function analysis, Notch activation patterns were correlated with
      function during development, self-renewal and malignancy in selected tissues.
      Identification of many known functions of Notch1 throughout development validated
      the utility of this approach. Importantly, novel roles for Notch1 signaling were
      identified in heart, vasculature, retina and in the stem cell compartments of
      self-renewing epithelia. We find that the probability of Notch1 activation in
      different tissues does not always indicate a requirement for this receptor and
      that gradients of Notch1 activation are evident within one organ. These findings
      highlight an underappreciated layer of complexity of Notch signaling in vivo.
      Moreover, NIP-CRE represents a general strategy applicable for monitoring
      proteolysis-dependent signaling in vivo.

PMID- 17215308
TI  - The glycosyltransferase Fringe promotes Delta-Notch signaling between neurons and
      glia, and is required for subtype-specific glial gene expression.
AB  - The development, organization and function of central nervous systems depend on
      interactions between neurons and glial cells. However, the molecular signals that
      regulate neuron-glial communication remain elusive. In the ventral nerve cord of
      Drosophila, the close association of the longitudinal glia (LG) with the neuropil
      provides an excellent opportunity to identify and characterize neuron-glial
      signals in vivo. We have found that the activity and restricted expression of the
      glycosyltransferase Fringe (Fng) renders a subset of LG sensitive to activation
      of signaling through the Notch (N) receptor. This is the first report showing
      that modulation of N signaling by Fng is important for central nervous system
      development in any organism. In each hemisegment of the nerve cord the
      transcription factor Prospero (Pros) is selectively expressed in the six most
      anterior LG. Pros expression is specifically reduced in fng mutants, and is
      blocked by antagonism of the N pathway. The N ligand Delta (Dl), which is
      expressed by a subset of neurons, cooperates with Fng for N signaling in the
      anterior LG, leading to subtype-specific expression of Pros. Furthermore, ectopic
      Pros expression in posterior LG can be triggered by Fng, and by Dl derived from
      neurons but not glia. This effect can be mimicked by direct activation of the N
      pathway within glia. Our genetic studies suggest that Fng sensitizes N on glia to
      axon-derived Dl and that enhanced neuron-glial communication through this ligand
      receptor pair is required for the proper molecular diversity of glial cell
      subtypes in the developing nervous system.

PMID- 17215309
TI  - Hexamerin-based regulation of juvenile hormone-dependent gene expression
      underlies phenotypic plasticity in a social insect.
AB  - Worker termites of the genus Reticulitermes are temporally-arrested juvenile
      forms that can terminally differentiate into adultsoldier- or reproductive-caste
      phenotypes. Soldier-caste differentiation is a developmental transition that is
      induced by high juvenile hormone (JH) titers. Recently, a status quo hexamerin
      mechanism was identified, which reduces JH efficacy and maximizes colony fitness
      via the maintenance of high worker-caste proportions. Our goal in these studies
      was to investigate more thoroughly the influences of the hexamerins on JH
      dependent gene expression in termite workers. Our approach involved RNA
      interference (RNAi), bioassays and quantification of gene expression. We first
      investigated the expression of 17 morphogenesis-associated genes in response to
      RNAi-based hexamerin silencing. Hexamerin silencing resulted in significant
      downstream impacts on 15 out of the 17 genes, suggesting that these genes are
      members of a JH-responsive genomic network. Next, we compared gene-expression
      profiles in workers after RNAi-based hexamerin silencing to that of (i) untreated
      workers that were held away from the colony; and (ii) workers that were also held
      away from the colony, but with ectopic JH. Here, although there was no
      correlation between hexamerin silencing and colony-release effects, we observed a
      significant correlation between hexamerin silencing and JH-treatment effects.
      These findings provide further evidence supporting the hypothesis that the
      hexamerins modulate JH availability, thus limiting the impacts of JH on termite
      caste polyphenism. Results are discussed in a context relative to outstanding
      questions on termite developmental biology, particularly on regulatory gene
      networks that respond to JH-, colony- and environmental-cues.

PMID- 17215310
TI  - Specification of epibranchial placodes in zebrafish.
AB  - In all vertebrates, the neurogenic placodes are transient ectodermal thickenings
      that give rise to sensory neurons of the cranial ganglia. Epibranchial (EB)
      placodes generate neurons of the distal facial, glossopharyngeal and vagal
      ganglia, which convey sensation from the viscera, including pharyngeal endoderm
      structures, to the CNS. Recent studies have implicated signals from pharyngeal
      endoderm in the initiation of neurogenesis from EB placodes; however, the signals
      underlying the formation of placodes are unknown. Here, we show that zebrafish
      embryos mutant for fgf3 and fgf8 do not express early EB placode markers,
      including foxi1 and pax2a. Mosaic analysis demonstrates that placodal cells must
      directly receive Fgf signals during a specific crucial period of development.
      Transplantation experiments and mutant analysis reveal that cephalic mesoderm is
      the source of Fgf signals. Finally, both Fgf3 and Fgf8 are sufficient to induce
      foxi1-positive placodal precursors in wild-type as well as Fgf3-plus Fgf8
      depleted embryos. We propose a model in which mesoderm-derived Fgf3 and Fgf8
      signals establish both the EB placodes and the development of the pharyngeal
      endoderm, the subsequent interaction of which promotes neurogenesis. The
      coordinated interplay between craniofacial tissues would thus assure proper
      spatial and temporal interactions in the shaping of the vertebrate head.

PMID- 17215311
TI  - Neurogenic role of Gcm transcription factors is conserved in chicken spinal cord.
AB  - Although glial cells missing (gcm) genes are known as glial determinants in the
      fly embryo, the role of vertebrate orthologs in the central nervous system is
      still under debate. Here we show for the first time that the chicken ortholog of
      fly gcm (herein referred to as c-Gcm1), is expressed in early neuronal lineages
      of the developing spinal cord and is required for neural progenitors to
      differentiate as neurons. Moreover, c-Gcm1 overexpression is sufficient to
      trigger cell cycle exit and neuronal differentiation in neural progenitors. Thus,
      c-Gcm1 expression constitutes a crucial step in the developmental cascade that
      prompts progenitors to generate neurons: c-Gcm1 acts downstream of proneural
      (neurogenin) and progenitor (Sox1-3) factors and upstream of NeuroM neuronal
      differentiation factor. Strikingly, this neurogenic role is not specific to the
      vertebrate gene, as fly gcm and gcm2 are also sufficient to induce the expression
      of neuronal markers. Interestingly, the neurogenic role is restricted to post
      embryonic stages and we identify two novel brain neuronal lineages expressing and
      requiring gcm genes. Finally, we show that fly gcm and the chick and mouse
      orthologs induce expression of neural markers in HeLa cells. These data, which
      demonstrate a conserved neurogenic role for Gcm transcription factors, call for a
      re-evaluation of the mode of action of these genes during evolution.

PMID- 17215312
TI  - Safety and tolerability of bosentan in idiopathic pulmonary fibrosis: an open
      label study.
AB  - Idiopathic pulmonary fibrosis (IPF) is a fatal disease for which no effective
      treatment exists. In the present study, 12 IPF patients underwent analysis of gas
      exchange properties using the multiple inert gas elimination technique on day 1
      before and after the administration of 125 mg bosentan, a dual endothelin
      antagonist. Following this, patients received chronic administration for 12 weeks
      (62.5 mg b.i.d. in week 1, 125 mg b.i.d. thereafter). The primary objective was
      to determine the effect of bosentan on gas exchange (day 1) and on oxygen
      saturation and minute ventilation (week 2). With one exception, where
      redistribution of total pulmonary blood flow from normal ventilation/perfusion
      (V'/Q') areas (93% before, 72% after bosentan) to low V'/Q' areas (0% before,
      22.2% after) was encountered, no patient showed any change in gas exchange
      (mean+/-SD shunt flow (% of cardiac output) 8.5+/-3.4% before, 6.1+/-2.3% after
      bosentan; day 1) or oxygen saturation and minute ventilation (week 2). Similarly,
      none of the secondary parameters was significantly changed either at week 2 or at
      the end of the study period (week 12). Five patients developed respiratory
      infections and two died because of pneumonia; this was judged as being unrelated
      to bosentan intake. In conclusion, bosentan administration does not seem to
      induce clinically relevant gas exchange abnormalities in idiopathic pulmonary
      fibrosis patients.

PMID- 17215313
TI  - A prediction rule for elderly primary-care patients with lower respiratory tract
      infections.
AB  - Prognostic scores for lower respiratory tract infections (LRTI) have been mainly
      derived in a hospital setting. The current authors have developed and validated a
      prediction rule for the prognosis of acute LRTI in elderly primary-care patients.
      Data including demographics, medication use, healthcare use and comorbid
      conditions from 3,166 episodes of patients aged > or =65 yrs visiting the general
      practitioner (GP) with LRTI were collected. Multiple logistic regression analysis
      was used to construct a predictive model. The main outcome measure was 30-day
      hospitalisation or death. The Second Dutch Survey of GPs was used for validation.
      The following were independent predictors of 30-day hospitalisation or death:
      increasing age; previous hospitalisation; heart failure; diabetes; use of oral
      glucocorticoids; previous use of antibiotics; a diagnosis of pneumonia; and
      exacerbation of chronic obstructive pulmonary disease. A prediction rule based on
      these variables showed that the outcome increased directly with increasing
      scores: 3, 10 and 31% for scores of <2 points, 3-6 and > or =7 points,
      respectively. Corresponding figures for the validation cohort were 3, 11 and 26%,
      respectively. This simple prediction rule can help the primary-care physician to
      differentiate between high- and low-risk patients. As a possible consequence, low
      risk patients may be suitable for home treatment, whereas high-risk patients
      might be monitored more closely in a homecare or hospital setting. Future studies
      should assess whether information on signs and symptoms can further improve this
      prediction rule.

PMID- 17215314
TI  - Effect of tuberculin skin testing on a Mycobacterium tuberculosis-specific
      interferon-gamma assay.
AB  - Recently, interferon-gamma release assays (IGRA) for specific diagnosis of
      Mycobacterium tuberculosis infection have become available. In recent UK
      tuberculosis (TB) guidelines, it has been advised to screen for latent M.
      tuberculosis infection using the tuberculin skin test (TST), followed by IGRA if
      the TST is positive. Since TST can boost immune responses to tuberculin, the
      present authors evaluated whether TST administration affects the result of
      QuantiFERON-TB Gold in-tube (QFT-GIT), a whole blood-based IGRA. QFT-GIT was
      performed on the day of TST administration and the day of reading in 15 TST
      negative subjects, 46 TST-positive subjects with recent or remote exposure to M.
      tuberculosis and five cured TB patients. No systematic boosting of QFT-GIT
      responses from negative to positive was observed. Only in a few TST-positive
      persons did TST enhance pre-existing QFT-GIT responses. Screening for latent
      Mycobacterium tuberculosis infection using tuberculin skin testing followed by
      interferon-gamma release assays on the day of reading is a reliable approach, as
      the specificity of QuantiFERON-TB Gold in-tube is not affected by prior
      tuberculin skin test administration.

PMID- 17215315
TI  - The autoclavable semirigid thoracoscope: the way forward in pleural disease?
AB  - Medical thoracoscopy is a valuable tool in the investigation and management of
      pleural disease. It has considerable advantages over conventional blind pleural
      biopsy and video-assisted thoracoscopic surgery. Despite this, the practice of
      this technique in the UK is limited. Most operators use the rigid thoracoscope,
      which may be an unfamiliar instrument to respiratory physicians. A semirigid
      thoracoscope is available but its use has not been possible in the UK as it
      requires sterilisation with ethylene oxide, which is not approved in this
      country. The present authors describe herein their experience with the first ever
      autoclavable semirigid thoracoscope. Medical thoracoscopy using the new
      instrument was performed in 56 patients between June 2004 and May 2006. All
      patients had been referred with a unilateral pleural effusion of unknown
      aetiology, where blind pleural aspiration had failed to yield an answer.
      Diagnostic samples were taken and talc poudrage performed where appropriate. The
      instrument was easy to handle and excellent views were obtained. Histologically
      adequate biopsy samples were obtained in 54 patients. The combination of clinical
      features, computed tomography findings and thoracoscopic biopsy enabled a
      definite diagnosis in 49 (90.7%) of these patients. There were no complications.
      The autoclavable semirigid thoracoscope has immense potential in the diagnosis
      and management of pleural disease. Its diagnostic yield in pleural disease is
      comparable to the conventional rigid thoracoscope. It is similar in design to the
      fibreoptic bronchoscope and respiratory physicians should be able to adapt to its
      use easily. It is also compatible with existing video processors and light
      sources available in most endoscopy suites. The fact that this instrument is
      autoclavable should open the field for its use in the UK as well as in other
      countries.

PMID- 17215316
TI  - Socioeconomic status, asthma and chronic bronchitis in a large community-based
      study.
AB  - The present study investigated the relationship between socioeconomic status,
      using measures of occupational class and education level, and the prevalence and
      incidence of asthma (with and without atopy) and chronic bronchitis using data
      from the European Community Respiratory Health Survey (ECRHS). Asthma and chronic
      bronchitis were studied prospectively within the ECRHS (n = 9,023). Incidence
      analyses comprised subjects with no history of asthma or bronchitis at baseline.
      Asthma symptoms were also assessed as a continuous score. Bronchitis risk was
      associated with low educational level (prevalence odds ratio (POR) 1.9; 95%
      confidence interval (CI) 1.4-2.8) and occupational class (1.8; 1.2-2.7). Incident
      bronchitis also increased with low educational level (risk ratio (RR) 2.8; 95%CI
      1.5-5.4). Prevalent and incident asthma with no atopy were associated with low
      educational level. Subjects in the low occupational class (incident risk ratio
      (IRR) 1.4; 95%CI 1.2-1.7) and education group (IRR 1.3; 95% CI 1.1-1.6) had
      higher mean asthma scores than those in higher socioeconomic groups. Lower
      educational level was associated with increased risk of prevalent and incident
      chronic bronchitis and asthma with no atopy. Lower socioeconomic groups tended to
      have a higher prevalence and incidence of asthma, particularly higher mean asthma
      scores. Adjustment for variables associated with asthma and bronchitis explained
      little of the observed health differences by socioeconomic status.

PMID- 17215318
TI  - Genetics of parentally reported asthma, eczema and rhinitis in 5-yr-old twins.
AB  - The aim of the present study was to examine the genetic and environmental
      contributions to the individual differences in susceptibility to asthma, eczema
      and rhinitis in childhood and their role in the association among these
      conditions. Information on asthma, eczema and rhinitis was obtained by parental
      report. Parents were asked whether a physician had ever diagnosed the condition.
      Complete data were available for 8,633 5-yr-old twin pairs born between 1986 and
      1998. The frequency of parentally reported asthma, eczema and rhinitis was 8.7,
      16.8 and 4.4%, respectively, and was higher in males than females. Genetic
      factors accounted for approximately 90% of the variance in the susceptibility to
      asthma, eczema and rhinitis. The magnitude of genetic factors did not differ
      between males and females. The remaining part of the variance was explained by
      environmental factors not shared by family members. The phenotypic correlations
      between parentally reported asthma, eczema and rhinitis were moderate and mainly
      mediated by the same genetic factors. The high heritability and the limited
      influence of shared environmental factors may point to gene x environment
      interactions. Future research should focus on this type of interaction processes.

PMID- 17215317
TI  - Release of the antimicrobial peptide LL-37 from DNA/F-actin bundles in cystic
      fibrosis sputum.
AB  - Cationic antibacterial peptides (ABPs) are secreted in the airways and function
      in the first line of defence against infectious agents. They attack multiple
      molecular targets to cooperatively penetrate and disrupt microbial surfaces and
      membrane barriers. Antibacterial properties of ABPs, including cathelicidin LL
      37, are reduced in cystic fibrosis (CF) airways as a result of direct interaction
      with DNA and filamentous (F)-actin. Microscopic evaluation of a mixed solution of
      DNA and F-actin, after the addition of rhodamine-B-labelled LL-37 peptide,
      revealed the presence of a bundle structure similar to that present in CF sputum.
      Analysis of CF sputum after centrifugation showed that LL-37 was mostly bound to
      components of the pellet fraction containing DNA, F-actin and cell remnants.
      Factors that dissolve DNA/actin bundles and fluidise CF sputum, such as Dornase
      alfa (recombinant human DNase I), gelsolin, polyaspartate or their combinations,
      increased the amount of LL-37 peptide detected in the supernatant of CF sputum.
      The presence of the bacterial endotoxin lipopolysaccharide (LPS) in CF sputum and
      the ability of LPS to inhibit the antibacterial activity of LL-37 suggests that
      inactivation of LL-37 function in CF sputum partially results from its
      interaction with LPS. LL-37-LPS interaction was prevented by an LPS-binding
      protein (LBP)-derived peptide known for its ability to neutralise LPS, whereas
      LBPW91A, a mutant peptide that lacks ability to bind LPS, had no effect. A
      combination of factors that dissolve DNA/filamentous-actin aggregates together
      with lipopolysaccharide-binding agents may represent a potential treatment for
      the chronic infections that occur in cystic fibrosis airways.

PMID- 17215319
TI  - Telomere length is associated with left ventricular function in the oldest old:
      the Newcastle 85+ study.
AB  - AIMS: Heart failure is a condition increasingly prevalent at older ages; however,
      mechanisms by which the ageing process affects cardiac function are largely
      unknown. Telomere length is a biomarker of ageing that has been suggested to be
      associated with a variety of diseases of late onset, but its relationship with
      cardiac function has not previously been studied. We measured telomere length in
      peripheral blood mononuclear cells and carried out echocardiography in a group of
      85-year old subjects recruited from the community as part of the Newcastle 85+
      Study. METHODS AND RESULTS: Eighty-nine subjects were recruited through local
      family practitioners. They were visited in their homes for clinical assessment
      and echocardiography, which was performed using a handheld device. Telomere
      length was measured by a real-time PCR method. High sensitivity C-reactive
      protein was measured using ELISA. Echocardiographic M-mode ejection fraction (EF)
      was strongly associated with telomere length (P=0.006) in subjects without
      evidence of previous MI. Sex and telomere length were significant predictors of
      EF while current smoking, blood pressure, plasma high sensitivity C-reactive
      protein, and use of cardiovascular medications were not. One standard deviation
      longer telomeres were associated with a 5% higher EF. Telomere length accounted
      for 12% of the observed variability in EF. CONCLUSION: These data show influences
      of the ageing process on myocardial function in the oldest old, apparently
      independent of other specific disease processes. This may be of importance in the
      aetiology of heart failure in this age group.

PMID- 17215320
TI  - Substantia nigra osmoregulation: taurine and ATP involvement.
AB  - An extracellular nonsynaptic taurine pool of glial origin was recently reported
      in the substantia nigra (SN). There is previous evidence showing taurine as an
      inhibitory neurotransmitter in the SN, but the physiological role of this
      nonsynaptic pool of taurine has not been explored. By using microdialysis
      methods, we studied the action of local osmolarity on the nonsynaptic taurine
      pool in the SN of the rat. Hypoosmolar pulses (285-80 mosM) administered in the
      SN by the microdialysis probe increased extrasynaptic taurine in a dose-dependent
      way, a response that was counteracted by compensating osmolarity with choline.
      The opposite effect (taurine decrease) was observed when osmolarity was
      increased. Under basal conditions, the blockade of either the AMPA-kainate
      glutamate receptors with 6-cyano-7-nitroquinoxaline-2,3-dionine disodium or the
      purinergic receptors with pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid
      modified the taurine concentration, suggesting that both receptors modulate the
      extrasynaptic pool of taurine. In addition, these drugs decreased the taurine
      response to hypoosmolar pulses, suggesting roles for glutamatergic and purinergic
      receptors in the taurine response to osmolarity. The participation of purinergic
      receptors was also supported by the fact that ATP (which, under basal conditions,
      increased the extrasynaptic taurine in a dose-dependent way) administered in
      doses saturating purinergic receptors also decreased the taurine response to
      hypoosmolarity. Taken together, present data suggest osmoregulation as a role of
      the nonsynaptic taurine pool of the SN, a function that also involves glutamate
      and ATP and that could influence the nigral cell vulnerability in Parkinson's
      disease.

PMID- 17215321
TI  - Changes in regulation of sodium/calcium exchanger of avian ventricular heart
      cells during embryonic development.
AB  - It has been suggested that the sodium/calcium exchanger NCX1 may have a more
      important physiological role in embryonic and neonatal hearts than in adult
      hearts. However, in chick heart sarcolemmal vesicles, sodium-dependent calcium
      transport is reported to be small and, moreover, to be 3-12 times smaller in
      hearts at embryonic day (ED) 4-5 than at ED18, the opposite of what would be
      expected of a transporter that is more important in early development. To better
      assess the role of NCX1 in calcium regulation in the chick embryonic heart, we
      measured the activity of NCX1 in chick embryonic hearts as extracellular calcium
      activated exchanger current (I(NCX)) under controlled ionic conditions. With
      intracellular calcium concentration ([Ca(2+)](i)) = 47 nM, I(NCX) density
      increased from 1.34 +/- 0.28 pA/pF at ED2 to 3.22 +/- 0.55 pA/pF at ED11 (P =
      0.006); however, with [Ca(2+)](i) = 481 nM, the increase was small and
      statistically insignificant, from 4.54 +/- 0.77 to 5.88 +/- 0.73 pA/pF (P = 0.20,
      membrane potential = 0 mV, extracellular calcium concentration = 2 mM). Plots of
      I(NCX) density against [Ca(2+)](i) were well fitted by the Michaelis-Menton
      equation and extrapolated to identical maximal currents for ED2 and ED11 cells
      (extracellular calcium concentration = 1, 2, or 4 mM). Thus the increase in
      I(NCX) at low [Ca(2+)](i) appeared to reflect a developmental change in
      allosteric regulation of the exchanger by intracellular calcium rather than an
      increase in the membrane density of NCX1. Supporting this conclusion, RT-PCR
      demonstrated little change in the amount of mRNA encoding NCX1 expression from
      ED2 through ED18.

PMID- 17215322
TI  - Actin-dependent regulation of connective tissue growth factor.
AB  - Expression of connective tissue growth factor (CTGF) in endothelial cells is
      modulated by shear stress affecting the organization of the cytoskeleton. The
      molecular connection between alterations of actin and CTGF expression was
      investigated in human umbilical vein endothelial cells (HUVEC) and a
      microvascular endothelial cell line. Overexpression of nonpolymerizable monomeric
      actin R62D interfered with stress fiber formation in HUVEC and concomitantly
      reduced immunoreactive CTGF. In microvascular endothelial cells, flow-dependent
      upregulation of CTGF was prevented by this actin mutant. In contrast,
      overexpression of actin S14C strengthened filamentous actin and increased CTGF
      expression. These data indicated an inverse relationship between CTGF expression
      and monomeric actin. Coexpression of the mutant actins and different CTGF
      promoter constructs revealed an actin-sensitive site between 3 and 4.5 kb of the
      CTGF promoter. A CArG-like box at -3791 bp was responsible for actin-dependent
      CTGF induction as shown by mutagenesis. Overexpression of actin S14C activated
      the nonmutated promoter significantly more strongly than the mutated promoter.
      Actin polymerization is regulated by the small GTPase RhoA and activation of
      serum response factor (SRF). Overexpression of constitutively active RhoA or SRF
      significantly increased CTGF protein synthesis. The 4.5-kb promoter construct,
      but not the construct with a mutation in the CArG box, was activated by SRF or
      RhoA, providing evidence for a functional role of this site in CTGF induction.
      These findings provide novel evidence that monomeric actin is the connecting link
      between alterations in the cytoskeleton and CTGF gene expression and demonstrate
      the importance of SRF in regulating CTGF transcription.

PMID- 17215323
TI  - Tin protoporphyrin induces intestinal chloride secretion by inducing light
      oxidation processes.
AB  - Heme induces Cl(-) secretion in intestinal epithelial cells, most likely via
      carbon monoxide (CO) generation. The major source of endogenous CO comes from the
      degradation of heme via heme oxygenase (HO). We hypothesized that an inhibitor of
      HO activity, tin protoporphyrin (SnPP), may inhibit the stimulatory effect of
      heme on Cl(-) secretion. To test this hypothesis, we treated an intestinal
      epithelial cell line (Caco-2 cells) with SnPP. In contrast to our expectations,
      Caco-2 cells treated with SnPP had an increase in their short-circuit currents
      (I(sc)) in Ussing chambers. This effect was observed only when the system was
      exposed to ambient light. SnPP-induced I(sc) was caused by Cl(-) secretion
      because it was inhibited in Cl(-)-free medium, with ouabain or 5-nitro-2-(3
      phenylpropylamino)benzoic acid (NPPB). The Cl(-) secretion was not via activation
      of the CFTR, because a specific inhibitor had no effect. Likewise, inhibitors of
      adenylate cyclase and guanylate cyclase had no effect on the enhanced I(sc). SnPP
      induced I(sc) was inhibited by the antioxidant vitamins, alpha-tocopherol and
      ascorbic acid. Electron paramagnetic resonance experiments confirmed that
      oxidative reactions were initiated with light in cells loaded with SnPP. These
      data suggest that SnPP-induced effects may not be entirely due to the inhibition
      of HO activity but rather to light-induced oxidative processes. These novel
      effects of SnPP-photosensitized oxidation may also lead to a new understanding of
      how intestinal Cl(-) secretion can be regulated by the redox environment of the
      cell.

PMID- 17215324
TI  - Src and focal adhesion kinase mediate mechanical strain-induced proliferation and
      ERK1/2 phosphorylation in human H441 pulmonary epithelial cells.
AB  - Pulmonary epithelial cells are exposed to repetitive deformation during
      physiological breathing and mechanical ventilation. Such deformation may
      influence pulmonary growth, development, and barotrauma. Although deformation
      stimulates proliferation and activates extracellular signal-regulated kinases
      (ERK1/2) in human pulmonary epithelial H441 cells, the upstream mechanosensors
      that induce ERK activation are poorly understood. We investigated whether c-Src
      or focal adhesion kinase (FAK) mediates cyclic mechanical strain-induced ERK1/2
      activation and proliferation in human pulmonary epithelial (NCI-H441) cells. The
      H441 and A549 cells were grown on collagen I-precoated membranes and were
      subjected to an average 10% cyclic mechanical strain at 20 cycles/min. Cyclic
      strain activated Src within 2 min by increasing phosphorylation at Tyr(418),
      followed by rapid phosphorylation of FAK at Tyr(397) and Tyr(576) and ERK1/2 at
      Thr(202)/Tyr(204) (n = 5, P < 0.05). Twenty-four (A549 cells) and 24-72 h (H441
      cells) of cyclic mechanical strain increased cell numbers compared with static
      culture. Twenty-four hours of cyclic strain also increased H441 FAK, Src, and ERK
      phosphorylation without affecting total FAK, Src, or ERK protein. The mitogenic
      effect was blocked by Src (10 micromol/l PP2 or short interfering RNA targeted to
      Src) or MEK (50 micromol/l PD-98059) inhibition. PP2 also blocked strain-induced
      phosphorylation of FAK-Tyr(576) and ERK-Thr(202)/Tyr(204) but not FAK-Tyr(397).
      Reducing FAK by FAK-targeted short interfering RNA blocked mechanical strain
      induced mitogenicity and significantly attenuated strain-induced ERK activation
      but not strain-induced Src phosphorylation. Together, these results suggest that
      repetitive mechanical deformation induced by ventilation supports pulmonary
      epithelial proliferation by a pathway involving Src, FAK, and then ERK signaling.

PMID- 17215325
TI  - Inhibition of zipper-interacting protein kinase function in smooth muscle by a
      myosin light chain kinase pseudosubstrate peptide.
AB  - As a regulator of smooth muscle contractility, zipper-interacting protein kinase
      (ZIPK) appears to phosphorylate the regulatory myosin light chain (RLC20),
      directly or indirectly, at Ser19 and Thr18 in a Ca(2+)-independent manner. The
      calmodulin-binding and autoinhibitory domain of myosin light chain kinase (MLCK)
      shares similarity to a sequence found in ZIPK. This similarity in sequence
      prompted an investigation of the SM1 peptide, which is derived from the
      autoinhibitory region of MLCK, as a potential inhibitor of ZIPK. In vitro studies
      showed that SM1 is a competitive inhibitor of a constitutively active 32-kDa form
      of ZIPK with an apparent K(i) value of 3.4 microM. Experiments confirmed that the
      SM1 peptide is also active against full-length ZIPK. In addition, ZIPK
      autophosphorylation was reduced by SM1. ZIPK activity is independent of
      calmodulin; however, calmodulin suppressed the in vitro inhibitory potential of
      SM1, likely as a result of nonspecific binding of the peptide to calmodulin.
      Treatment of ileal smooth muscle with exogenous ZIPK was accompanied by an
      increase in RLC20 diphosphorylation, distinguishing between ZIPK [and integrin
      linked kinase (ILK)] and MLCK actions. Administration of SM1 suppressed steady
      state muscle tension developed by the addition of exogenous ZIPK to Triton
      skinned rat ileal muscle strips with or without calmodulin depletion by
      trifluoperazine. The decrease in contractile force was associated with decreases
      in both RLC20 mono- and diphosphorylation. In summary, we present the SM1 peptide
      as a novel inhibitor of ZIPK. We also conclude that the SM1 peptide, which has no
      effect on ILK, can be used to distinguish between ZIPK and ILK effects in smooth
      muscle tissues.

PMID- 17215326
TI  - NF-kappaB activation by depolarization of skeletal muscle cells depends on
      ryanodine and IP3 receptor-mediated calcium signals.
AB  - Depolarization of skeletal muscle cells by either high external K(+) or
      repetitive extracellular field potential pulses induces calcium release from
      internal stores. The two components of this release are mediated by either
      ryanodine receptors or inositol 1,4,5-trisphosphate (IP(3)) receptors and show
      differences in kinetics, amplitude, and subcellular localization. We have
      reported that the transcriptional regulators including ERKs, cAMP/Ca(2+)-response
      element binding protein, c-fos, c-jun, and egr-1 are activated by K(+)-induced
      depolarization and that their activation requires IP(3)-dependent calcium
      release. We presently describe the activation of the nuclear transcription factor
      NF-kappaB in response to depolarization by either high K(+) (chronic) or
      electrical pulses (fluctuating). Calcium transients of relative short duration
      activate an NF-kappaB reporter gene to an intermediate level, whereas long
      lasting calcium increases obtained by prolonged electrical stimulation protocols
      of various frequencies induce maximal activation of NF-kappaB. This activation is
      independent of extracellular calcium, whereas calcium release mediated by either
      ryanodine or IP(3) receptors contribute in all conditions tested. NF-kappaB
      activation is mediated by IkappaBalpha degradation and p65 translocation to the
      nucleus. Partial blockade by N-acetyl-l-cysteine, a general antioxidant, suggests
      the participation of reactive oxygen species. Calcium-dependent signaling
      pathways such as those linked to calcineurin and PKC also contribute to NF-kappaB
      activation by depolarization, as assessed by blockade through pharmacological
      agents. These results suggest that NF-kappaB activation in skeletal muscle cells
      is linked to membrane depolarization and depends on the duration of elevated
      intracellular calcium. It can be regulated by sequential activation of calcium
      release mediated by the ryanodine and by IP(3) receptors.

PMID- 17215327
TI  - Beta-defensin overexpression induces progressive muscle degeneration in mice.
AB  - Defensins comprise a family of cationic antimicrobial peptides characterized by
      conserved cysteine residues. They are produced in various organs including
      skeletal muscle and are identified as key elements in the host defense system as
      potent effectors. At the same time, defensins have potential roles in the
      regulation of inflammation and, furthermore, can exert cytotoxic effects on
      several mammalian cells. Here, we developed transgenic mice overexpressing mouse
      beta-defensin-6 to explore the pathophysiological roles of the defensin family as
      a novel mediator of inflammatory tissue injury. Unexpectedly, the transgenic mice
      showed short lifespan, poor growth, and progressive myofiber degeneration with
      functional muscle impairment, predominant centronucleated myofibers, and elevated
      serum creatine kinase activity, as seen in human muscular dystrophy. Furthermore,
      some of the transgenic myofibers showed IkappaBalpha accumulation, which would be
      related to the myofiber apoptosis of limb-girdle muscular dystrophy type 2A. The
      present findings may unravel a concealed linkage between the innate immune system
      and the pathophysiology of degenerative diseases.

PMID- 17215328
TI  - Isoflurane preconditioning uncouples mitochondria and protects against hypoxia
      reoxygenation.
AB  - Ischemic cardiac injury can be substantially alleviated by exposing the heart to
      pharmacological agents such as volatile anesthetics before occurrence of ischemia
      reperfusion. A hallmark of this preconditioning phenomenon is its memory, when
      cardioprotective effects persist even after removal of preconditioning stimulus.
      Since numerous studies pinpoint mitochondria as crucial players in protective
      pathways of preconditioning, the aim of this study was to investigate the effects
      of preconditioning agent isoflurane on the mitochondrial bioenergetic phenotype.
      Endogenous flavoprotein fluorescence, an indicator of mitochondrial redox state,
      was elevated to 195 +/- 16% of baseline upon isoflurane application in intact
      cardiomyocytes, indicating more oxidized state of mitochondria. Isoflurane
      treatment also elicited partial dissipation of mitochondrial transmembrane
      potential, which remained depolarized even after anesthetic withdrawal
      (tetramethylrhodamine fluorescence intensity declined to 83 +/- 3 and 81 +/- 7%
      of baseline during isoflurane exposure and washout, respectively). Mild
      uncoupling, with preserved ATP synthesis, was also detected in mitochondria that
      were isolated from animals that had been previously preconditioned by isoflurane
      in vivo, revealing its memory nature. These mitochondria, after exposure to
      hypoxia and reoxygenation, exhibited better preserved respiration and ATP
      synthesis compared with mitochondria from nonpreconditioned animals. Partial
      mitochondrial depolarization was paralleled by a diminished Ca(2+) uptake into
      isoflurane-treated mitochondria, as indicated by the reduced increment in rhod-2
      fluorescence when mitochondria were challenged with increased Ca(2+) (180 +/- 24
      vs. 258 +/- 14% for the control). In conclusion, isoflurane preconditioning
      elicits partial mitochondrial uncoupling and reduces mitochondrial Ca(2+) uptake.
      These effects are likely to reduce the extent of the mitochondrial damage after
      the hypoxic stress.

PMID- 17215329
TI  - Interplay between TonEBP and calcineurin-NFATc signaling pathways: a means of
      optimizing water reabsorption? Focus on "Calcineurin-NFATc signaling pathway
      regulates AQP2 expression in response to calcium signals and osmotic stress".

PMID- 17215330
TI  - Regulation of chloride ion conductance during skeletal muscle development and in
      disease. Focus on "Chloride channelopathy in myotonic dystrophy resulting from
      loss of posttranscriptional regulation for CLCN1".

PMID- 17215331
TI  - Impact of nonignorable coarsening on Bayesian inference.
AB  - The coarse data model of Heitjan and Rubin (1991) generalizes the missing data
      model of Rubin (1976) to cover other forms of incompleteness such as censoring
      and grouping. The model has 2 components: an ideal data model describing the
      distribution of the quantity of interest and a coarsening mechanism that
      describes a distribution over degrees of coarsening given the ideal data. The
      coarsening mechanism is said to be nonignorable when the degree of coarsening
      depends on an incompletely observed ideal outcome, in which case failure to
      properly account for it can spoil inferences. A theme in recent research is to
      measure sensitivity to nonignorability by evaluating the effect of a small
      departure from ignorability on the maximum likelihood estimate (MLE) of a
      parameter of the ideal data model. One such construct is the "index of local
      sensitivity to nonignorability" (ISNI) (Troxel and others, 2004), which is the
      derivative of the MLE with respect to a nonignorability parameter evaluated at
      the ignorable model. In this paper, we adapt ISNI to Bayesian modeling by instead
      defining it as the derivative of the posterior expectation. We propose the
      application of ISNI as a first step in judging the robustness of a Bayesian
      analysis to nonignorable coarsening. We derive formulas for a range of models and
      apply the method to evaluate sensitivity to nonignorable coarsening in 2 real
      data examples, one involving missing CD4 counts in an HIV trial and the other
      involving potentially informatively censored relapse times in a leukemia trial.

PMID- 17215332
TI  - Ability of monocyte-derived dendritic cells to secrete oxygen radicals in
      response to formyl peptide receptor family agonists compared to that of myeloid
      and plasmacytoid dendritic cells.
AB  - We show that human monocyte-derived dendritic cells (DC) differ considerably from
      freshly isolated blood-derived myeloid and plasmacytoid DC in their abilities to
      produce reactive oxygen species in response to different agonists to the formyl
      peptide receptor family and are thus poor representatives of blood DC in this
      field of research.

PMID- 17215333
TI  - Characterization of Anaplasma phagocytophilum major surface protein 5 and the
      extent of its cross-reactivity with A. marginale.
AB  - Major surface protein 5 (Msp5) of Anaplasma marginale is highly conserved in the
      genus Anaplasma and the antigen used in a commercially available competitive
      enzyme-linked immunosorbent assay (cELISA) for serologic identification of cattle
      with anaplasmosis. This study analyzes the degrees of conservation of Msp5 among
      various isolates of Anaplasma phagocytophilum and the extent of serologic cross
      reactivity between recombinant Msp5 (rMsp5) of Anaplasma marginale and A.
      phagocytophilum. The msp5 genes from various isolates of A. phagocytophilum were
      sequenced and compared. rMsp5 proteins of A. phagocytophilum and A. marginale
      were used separately in an indirect ELISA to detect cross-reactivity in serum
      samples from humans and dogs infected with A. phagocytophilum and cattle infected
      with A. marginale. Serum samples were also tested with a commercially available
      competitive ELISA that uses monoclonal antibody ANAF16C1. There were 100%
      sequence identities in the msp5 genes among all of the A. phagocytophilum
      isolates from the United States and a horse isolate from Sweden. Sheep isolates
      from Norway and dog isolates from Sweden were 99% identical to one another but
      differed in 17 base pairs from the United States isolates and the horse isolate.
      Serologic cross-reactivity was identified when serum samples from cattle infected
      with A. marginale were reacted with rMsp5 of A. phagocytophilum and when serum
      samples from humans and dogs infected with A. phagocytophilum were reacted with
      rMsp5 of A. marginale in an indirect-ELISA format. Serum samples from dogs or
      humans infected with A. phagocytophilum did not cross-react with rMsp5 of A.
      marginale when tested with the commercially available cELISA. These results
      suggest that rMsp5 of A. phagocytophilum is highly conserved among United States
      and European isolates and that serologic distinction between A. phagocytophilum
      and A. marginale infections cannot be accomplished if rMsp5 from either organism
      is used in an indirect ELISA.

PMID- 17215334
TI  - Use of mycelial-phase Sporothrix schenckii exoantigens in an enzyme-linked
      immunosorbent assay for diagnosis of sporotrichosis by antibody detection.
AB  - An enzyme-linked immunosorbent assay (ELISA) was developed for specific antibody
      detection in serum specimens of patients with sporotrichosis. The assay was made
      with mycelial-phase Sporothrix schenckii exoantigens and was tested against 90
      sera from patients with different clinical forms of sporotrichosis. Potential
      cross-reactions were analyzed with 72 heterologous sera from patients with
      paracoccidioidomycosis, cryptococcosis, aspergillosis, histoplasmosis,
      tuberculosis, and American tegumentary leishmaniasis, as well as 76 sera from
      healthy controls. We found a sensitivity of 97% and a specificity of 89% in this
      assay. Some cross-reactions were seen, as observed in other immunoassays for the
      diagnosis of sporotrichosis. The ELISA appears to be especially useful for
      cutaneous forms of disease, since these are not promptly diagnosed with available
      immunoprecipitation or agglutination techniques. These results suggest that the
      ELISA using mycelial-phase S. schenckii exoantigens is a very sensitive
      diagnostic tool for the serodiagnosis of sporotrichosis and can be used in
      conjunction with conventional methods of diagnosis, particularly in cases where
      cross-reactions or false-positive results are experienced with the serodiagnosis.

PMID- 17215335
TI  - DNA vaccine construct incorporating intercellular trafficking and intracellular
      targeting motifs effectively primes and induces memory B- and T-cell responses in
      outbred animals.
AB  - We developed a vaccine construct in which a BVP22 domain and an invariant-chain
      major histocompatibility complex class II-targeting motif capable of enhancing
      dendritic cell antigen uptake and presentation were fused to a sequence encoding
      a B- and T-cell antigen from the Anaplasma marginale major surface protein 1a and
      tested whether this construct would prime and expand immune responses in outbred
      calves. A single inoculation with this construct effectively primed the immune
      responses, as demonstrated by a significant enhancement of CD4(+) T-cell
      proliferation compared to that in calves identically inoculated but inoculated
      with a DNA construct lacking the targeting domains and compared to that in calves
      inoculated with an empty vector. These proliferative responses were mirrored by
      priming and expansion of gamma interferon-positive CD4(+) T cells and
      immunoglobulin G responses against the linked B-cell epitope. Priming by the
      single immunization induced memory that underwent rapid recall following
      reexposure to the antigen. These results demonstrate that DNA vaccines targeting
      key intercellular and intracellular events significantly enhance priming and
      expansion and support the feasibility of single-dose DNA immunization in outbred
      populations.

PMID- 17215336
TI  - Protection against porcine reproductive and respiratory syndrome virus (PRRSV)
      infection through passive transfer of PRRSV-neutralizing antibodies is dose
      dependent.
AB  - Previous work in our laboratory demonstrated that passive transfer of porcine
      reproductive and respiratory syndrome virus (PRRSV)-neutralizing antibodies (NA)
      protected pregnant sows against reproductive failure and conferred sterilizing
      immunity in sows and offspring. We report here on the dose requirement for
      protection by passive transfer with NA in young weaned pigs. The presence of a
      1:8 titer of PRRSV-NA in serum consistently protected pigs against viremia.
      Nevertheless, their lungs, tonsils, buffy coat cells, and peripheral lymph nodes
      contained replicating PRRSV similar to the infected control group. Likewise,
      these animals excreted infectious virus to sentinels similar to the infectivity
      control animals. In an attempt to reach complete protective immunity equivalent
      to that previously observed in sows, the pigs were transferred with a higher
      titer of PRRSV-NA (1:32), and even then apparent sterilizing immunity was
      attained in only 50% of the animals. In conclusion, the presence of anti-PRRSV-NA
      in serum with a titer of 1:8 is enough to block viremia but not peripheral tissue
      seeding and transmission to contact animals. While a relatively low level of NA
      in blood is capable of conferring sterilizing immunity against PRRSV in sows, the
      amount of NA necessary to obtain full protection of a young weaned pig would be
      significantly higher, suggesting that differences exist in the PRRSV pathogenesis
      between both age groups. In addition, the titer of NA could be a helpful
      parameter of protection in the assessment of PRRSV vaccines.

PMID- 17215337
TI  - Relationship between HLA polymorphisms and gamma interferon and interleukin-10
      cytokine production in healthy individuals after rubella vaccination.
AB  - We studied the association between HLA alleles and rubella-specific gamma
      interferon (IFN-gamma) (Th1) and interleukin-10 (IL-10) (Th2) cytokine responses
      among 106 healthy children (ages, 14 to 17 years) previously immunized with two
      doses of rubella vaccine. Antibody titers and cytokine responses to rubella
      vaccination were not sex or age dependent. Several class I HLA-A (*0201, *2402,
      *6801) alleles were significantly associated with rubella vaccine-induced IFN
      gamma secretion. Several class II HLA-DRB1 (*0101) and HLA-DQB1 (*0501) alleles
      were also suggestive of an association with IFN-gamma secretion. Alleles with
      potential associations with rubella-specific IL-10 production included HLA-A
      (*0201, *6801), HLA-B (*4901), and HLA-DRB1 (*1302). The class I A*0201 and
      A*6801 alleles were associated with both IFN-gamma and IL-10 secretion. These
      tentative associations need to be validated in larger studies with subjects of
      differing ethnicities. These results provide additional evidence that HLA genes
      may influence Th1- and Th2-specific cytokine response(s) following rubella
      immunization, which in turn can influence both cellular and humoral immune
      responses to rubella vaccination.

PMID- 17215338
TI  - Topical inhibition of nasal carbonic anhydrase affects the CO2 detection
      threshold in rats.
AB  - Previous studies indicate that Long-Evans rats can be operantly trained to
      discriminate inspired CO(2) concentrations as low as 0.5%. This ability has been
      proposed to be due to the presence of CO(2)-sensitive olfactory receptors that
      contain the enzyme carbonic anhydrase (CA). The objectives of the present study
      were as follows: 1) to determine whether Zucker rats could be operantly
      conditioned to discriminate low concentrations of CO(2) from control air and 2)
      to determine the rats' CO(2) detection thresholds before and after nasal
      perfusion of mammalian Ringers or methazolamide, a CA inhibitor. Rats were
      operantly trained to discriminate between 25% CO(2) and control air (0% CO(2))
      and were then subjected to various CO(2) concentrations (0.5-12.5%) to determine
      their CO(2) detection thresholds. The average (+/-standard error of mean)
      baseline CO(2) detection threshold of 7 Zucker rats was 0.48 +/- 0.07% CO(2),
      whereas the average CO(2) detection thresholds after nasal perfusion of either
      mammalian Ringers or 10(-2) M methazolamide were 1.41 +/- 0.30% and 5.92 +/-
      0.70% CO(2), respectively. The average CO(2) detection threshold after
      methazolamide was significantly greater (P<0.0001) than the baseline detection
      threshold. These findings demonstrate that like Long-Evans rats, Zucker rats can
      be trained to discriminate low concentrations of CO(2) and that inhibition of
      nasal CA reduces the ability of the rats to detect low concentrations (3.5% and
      below) but not higher concentrations of CO(2) (12.5%). These results add to the
      growing evidence that olfactory neurons exhibiting CA activity are CO(2)
      chemoreceptors sensitive to physiological concentrations of CO(2).

PMID- 17215339
TI  - Multi-virulence-locus sequence typing identifies single nucleotide polymorphisms
      which differentiate epidemic clones and outbreak strains of Listeria
      monocytogenes.
AB  - A recently developed multi-virulence-locus sequence typing (MVLST) method showed
      improved discriminatory power for subtyping genetically diverse Listeria
      monocytogenes isolates and identified epidemic clone II isolates associated with
      two recent U.S. multistate listeriosis outbreaks. To evaluate the ability of
      MVLST to distinguish other epidemic clones and outbreak strains of L.
      monocytogenes, 58 outbreak-related isolates from 14 outbreaks and 49 unrelated
      isolates were analyzed. Results showed that MVLST provided very high
      discriminatory power (0.99), epidemiological concordance (1.0), stability, and
      typeability. MVLST accurately identified three previously known epidemic clones
      (epidemic clones I, II, and III) and redefined another epidemic clone (epidemic
      clone IV) in serotype 4b of L. monocytogenes. A set of 28 single nucleotide
      polymorphisms (SNPs) differentiated all epidemiologically unrelated isolates. A
      subset of 16 SNPs differentiated all epidemic clones and outbreak strains.
      Phylogenetic analysis showed congruence between MVLST clusters, serotypes, and
      previously defined genetic lineages of L. monocytogenes. SNPs in virulence genes
      appear to be excellent molecular markers for the epidemiological investigation of
      epidemics and outbreaks caused by L. monocytogenes.

PMID- 17215340
TI  - Multiplex real-time PCR targeting the RNase P RNA gene for detection and
      identification of Candida species in blood.
AB  - We have developed a single-tube multiplex real-time PCR method for the detection
      of the eight most common Candida species causing septicemia: Candida albicans, C.
      dubliniensis, C. famata, C. glabrata, C. guilliermondii, C. krusei, C.
      parapsilosis, and C. tropicalis. The method developed targets the RNase P RNA
      gene RPR1. Sequences of this gene were determined for seven of the Candida
      species and showed surprisingly large sequence variation. C. glabrata was found
      to have a gene that was five times longer gene than those of the other species,
      and the nucleotide sequence similarity between C. krusei and C. albicans was as
      low as 55%. The multiplex PCR contained three probes that enabled the specific
      detection of C. albicans, C. glabrata, and C. krusei and a fourth probe that
      allowed the general detection of the remaining species. The method was able to
      detect 1 to 10 genome copies when the detection limit was tested repeatedly for
      the four species C. albicans, C. glabrata, C. krusei, and C. guilliermondii. No
      significant difference in the detection limit was seen when the multiplex format
      was compared with single-species PCR, i.e., two primers and one probe. The method
      detected eight clinically relevant Candida species and did not react with other
      tested non-Candida species or human DNA. The assay was applied to 20 blood
      samples from nine patients and showed a sensitivity similar to that of culture.

PMID- 17215341
TI  - Identification of alpha-hemolytic streptococci by pyrosequencing the 16S rRNA
      gene and by use of VITEK 2.
AB  - Alpha-hemolytic streptococci are very difficult to identify by phenotypic
      methods. In this study, a pyrosequencing method for the identification of
      streptococcal species based on two variable regions of the 16S rRNA gene is
      described. Almost all studied streptococcal species (n = 51) represented by their
      type strains could be differentiated except for some closely related species of
      the Streptococcus bovis or S. salivarius group. The pyrosequencing results of
      alpha-hemolytic streptococci isolated from blood (n = 99) or from the normal
      pharyngeal microbiota (n = 25) were compared to the results obtained by the VITEK
      2 with GP card (bioMerieux, Marcy l'Etoile, France). As expected, the results of
      the two methods did not completely agree, but 93 (75.0%) of the isolates assigned
      to the same streptococcal group by both methods and 57 (46.0%) reached consistent
      results at the species level. However, 10 strains remained unidentified by VITEK
      2, and 4 isolates could not be assigned to any streptococcal group by
      pyrosequencing. Identification of members of the S. mitis and S. sanguinis groups
      proved difficult for both methods. Furthermore, the pyrosequencing analysis
      revealed great sequence variation, since only 43 (32.3%) of the 133 isolates
      analyzed by pyrosequencing had sequences identical to a type strain. The
      variation was greatest in the pharyngeal isolates, slightly lower in the blood
      culture isolates, and nonexistent in invasive pneumococcal isolates (n = 17) that
      all had the S. pneumoniae type strain sequence. The resolution of the results
      obtained by the two methods is impeded by the lack of a proper gold standard.

PMID- 17215343
TI  - High prevalence of human bocavirus detected in young children with severe acute
      lower respiratory tract disease by use of a standard PCR protocol and a novel
      real-time PCR protocol.
AB  - The human bocavirus (HBoV) was recently isolated from respiratory tract samples.
      Within a study collective of children with severe lower respiratory tract
      disease, the patients testing positive for HBoV (12.8%) had a higher rate of
      underlying cardiopulmonary disease. Viral loads in respiratory tract specimens
      varied from 10(2) to 10(10) genome equivalents/ml.

PMID- 17215342
TI  - Correlation of Neo-Sensitabs tablet diffusion assay results on three different
      agar media with CLSI broth microdilution M27-A2 and disk diffusion M44-A results
      for testing susceptibilities of Candida spp. and Cryptococcus neoformans to
      amphotericin B, caspofungin, fluconazole, itraconazole, and voriconazole.
AB  - We compared the Neo-Sensitabs tablet assay to both reference M27-A2 broth
      microdilution and M44-A disk diffusion methods for testing susceptibilities of
      110 isolates of Candida spp. and Cryptococcus neoformans to amphotericin B,
      caspofungin, fluconazole, itraconazole, and voriconazole. Neo-Sensitabs assay
      inhibition zone diameters in millimeters on three agars (Mueller-Hinton agar
      supplemented with 2% dextrose and 0.5 microg/ml methylene blue [MGM], Shadomy
      [SHA], and RPMI 1640 [RPMI, 2% dextrose]) were obtained at 24 to 72 h. The
      correlation coefficient of Neo-Sensitabs results with MICs was similar to that of
      the disk method for most of the five agents on MGM (R, 0.80 to 0.89 versus 0.76
      to 0.89, respectively). Overall, superior correlation was observed at 24 h for
      most agents. The exception was amphotericin B (R values of 0.68 and 0.5 for disk
      and tablet, respectively, at 48 h versus 0.68 and 0.48, respectively, at 24 h).
      In general, Neo-Sensitabs results were less consistent on SHA and RPMI agars.
      Although agreement by breakpoint category of Neo-Sensitabs and disk results with
      CLSI method M27-A2 was also similar on MGM (92.7 to 98.2% versus 95.5 to 100%,
      respectively), the Neo-Sensitabs method failed to identify two of the six
      isolates with high amphotericin B MICs. These data suggest the potential value of
      the Neo-Sensitabs assay for testing at least four of the five agents against
      yeasts evaluated in the clinical laboratory.

PMID- 17215344
TI  - Multicenter comparison of the VITEK 2 yeast susceptibility test with the CLSI
      broth microdilution reference method for testing fluconazole against Candida spp.
AB  - A fully automated commercial antifungal susceptibility test system (VITEK 2 yeast
      susceptibility test; bioMerieux, Inc., Hazelwood, Mo.) was compared in three
      different laboratories with Clinical and Laboratory Standards Institute (CLSI)
      reference broth microdilution (BMD) method by testing two quality control strains
      and a total of 426 isolates of Candida spp. (103 to 135 clinical isolates in each
      laboratory plus 80 challenge isolates in one laboratory) against fluconazole.
      Reference BMD MIC endpoints were established after 24 and 48 h of incubation.
      VITEK 2 endpoints were determined spectrophotometrically after 10 to 26 h of
      incubation (mean, 13 h). Excellent essential agreement (within two dilutions)
      between the VITEK 2 and the 24- and 48-h BMD MICs was observed. The overall
      agreement values were 97.9 and 93.7%, respectively. Both intra- and
      interlaboratory agreement was 100%. The overall categorical agreement between
      VITEK 2 and BMD was 97.2% at the 24-h BMD time point and 88.3% at the 48-h BMD
      time point. Decreased categorical agreement at 48 h was attributed to trailing
      growth observed with Candida glabrata. The VITEK 2 system reliably detected
      fluconazole resistance among Candida spp. and demonstrated excellent quantitative
      and qualitative agreement with the reference BMD method.

PMID- 17215345
TI  - Cost-effective real-time reverse transcriptase PCR (RT-PCR) to screen for Dengue
      virus followed by rapid single-tube multiplex RT-PCR for serotyping of the virus.
AB  - Virus detection methodology provides detection of dengue virus in the early phase
      of the disease. PCR, targeting cDNA derived from viral RNA, has been used as a
      laboratory-based molecular tool for the detection of Dengue virus. We report the
      development and use of three real-time one-step reverse transcriptase PCR (RT
      PCR) assays to detect dengue cases and serotype the virus involved. The first RT
      PCR assay uses SYBR green I as the reporting dye for the purpose of cost
      effective screening for dengue virus. The detection limit of the SYBR green I
      assay was 10 PFU/ml (0.01 equivalent PFU per assay) for all four dengue virus
      serotypes. The second RT-PCR assay is a duplex fluorogenic probe-based real-time
      RT-PCR for serotyping clinical samples for dengue viruses. The detection
      threshold of the probe-based RT-PCR format was 0.1 PFU for serotypes Dengue-1 and
      Dengue-2, 1 PFU for serotype Dengue-3, and 0.01 PFU for serotype Dengue-4. The
      third is a fourplex assay that detects any of the four serotypes in a single
      closed tube with comparable sensitivity. Validation of the assays with local
      clinical samples collected from 2004 to 2006 revealed that there was an 88%
      positive correlation between virus isolation and RT-PCR with regard to dengue
      virus detection and a 100% correlation with seroconversion in subsequent samples.
      The serotyping results derived from duplex and fourplex assays agree fully with
      each other and with that derived from immunofluorescence assays.

PMID- 17215347
TI  - A nationwide epidemic of influenza C virus infection in Japan in 2004.
AB  - During the period from January to July 2004, a total of 131 influenza C viruses
      were detected by cell culture or reverse transcription-PCR (RT-PCR) from
      specimens that were obtained from children with acute respiratory symptoms in 10
      prefectures across Japan. Influenza C virus was identified most frequently in the
      Miyagi (1.4%, 45 of 3,226 specimens) and Yamagata (2.5%, 31 of 1,263 specimens)
      prefectures, and the frequency in this year was the highest since 1990.
      Phylogenetic analysis of the hemagglutinin esterase gene of the 13 strains
      isolated in nine prefectures revealed that genetically similar strains belonging
      to the Kanagawa/1/76-related lineage dominantly spread throughout Japan. During
      the 2004 influenza season, influenza C virus coexisted with epidemics of
      influenza A virus (H3 strain), and 12 cases were identified from patients who had
      been diagnosed with influenza-like illness (7 were detected by RT-PCR, and 5 were
      detected by culture). A comparison of specimens that were found positive by
      culture with those found positive only by RT-PCR shows that the amount of virus
      in PCR-positive specimens tended to be lower than in isolation-positive
      specimens. Although the mean peak temperature in patients in the PCR-positive
      group was slightly lower, there were no significant differences in
      characteristics between specimens (i.e., kind of specimen, period from onset to
      specimen collection, age distribution of patients, and severity of illness).
      These results suggest that an epidemic of influenza C virus occurred on a
      national scale during this period and that RT-PCR can be an effective
      supplemental tool for the evaluation of clinical and epidemiological information.

PMID- 17215346
TI  - Activity of dalbavancin tested against Staphylococcus spp. and beta-hemolytic
      Streptococcus spp. isolated from 52 geographically diverse medical centers in the
      United States.
AB  - Dalbavancin is a lipoglycopeptide antimicrobial agent with a potency
      significantly better than that of vancomycin when tested against staphylococci
      and streptococci. These two pathogens are common causes of skin and skin
      structure infections (SSSIs), and dalbavancin has been approved for the treatment
      of moderate to severe SSSIs. This study generated susceptibility data for
      staphylococci and beta-hemolytic streptococci from 52 U.S. medical centers that
      locally tested dalbavancin, vancomycin, and other antimicrobial class
      representatives to assess the potency of dalbavancin and the overall contemporary
      activities of commonly prescribed agents. Locally generated data showed that
      oxacillin-resistant staphylococci (57.0% overall) had slightly higher dalbavancin
      MIC(90) values (0.19 microg/ml) than oxacillin-susceptible strains (0.125
      microg/ml). This potency was 8- to 16-fold greater than that for vancomycin. beta
      Hemolytic streptococci had MIC(90) values ranging between <or=0.016 and 0.064
      microg/ml (highest for group B isolates). Levofloxacin, gentamicin, and
      tetracycline were active against oxacillin-susceptible staphylococci (82 to 99%
      susceptible), with lower susceptibility rates seen for the oxacillin-resistant
      strains. Linezolid coverage was >98% against staphylococci. Erythromycin
      resistance was high for staphylococci (30.6 to 94.1%) with inducible clindamycin
      resistance rates of 26.0% and 55.0% for oxacillin-susceptible and -resistant
      Staphylococcus aureus, respectively. Beta-hemolytic streptococci had a 20.2%
      erythromycin resistance rate and a 60% inducible clindamycin resistance rate but
      were highly susceptible to other tested agents. Etest reading errors were
      apparent and skewed results towards slightly higher dalbavancin MICs, requiring
      further education on how to interpret Etest method results for this compound.
      Current disk diffusion breakpoint criteria for oxacillin susceptibility for S.
      aureus showed a very-major-error rate of 2.3% and only a 0.9% minor-error rate
      when cefoxitin was used to predict oxacillin susceptibility. Dalbavancin
      demonstrated excellent potency and activity (100% susceptibility at proposed
      breakpoints) against common causes of SSSI pathogens in this U.S. multicenter
      study sample.

PMID- 17215349
TI  - A consensus view of protein dynamics.
AB  - The dynamics of proteins in aqueous solution has been investigated through a
      massive approach based on "state of the art" molecular dynamics simulations
      performed for all protein metafolds using the four most popular force fields
      (OPLS, CHARMM, AMBER, and GROMOS). A detailed analysis of the massive database of
      trajectories (>1.5 terabytes of data obtained using approximately 50 years of
      CPU) allowed us to obtain a robust-consensus picture of protein dynamics in
      aqueous solution.

PMID- 17215348
TI  - Contrasting geographic distribution profiles of the herpes simplex virus type 1
      BgOL and BgKL variants in Japan suggest dispersion and replacement.
AB  - Thelifelong latent infection-reactivation mode of infection of herpes simplex
      virus type 1 (HSV-1) transmitted by close contact has allowed a diversity of
      restriction fragment length polymorphism (RFLP) variations to accumulate in human
      populations. Whether and how the variants of the HSV-1 that is ubiquitous
      worldwide spread to different human populations is not clear. In our previous
      study the geographically gradient distribution of the HSV-1 BgK(L) variant, which
      is a good marker for the BgK(L):SaCFJ(M):SaGH(M):SaD/E(L):KpM(S) variant,
      suggested that BgK(L) dispersed geographically. Southern hybridization analyses
      showed that in BgK(L) the BglII cleavage site between the BglII K and small
      "Q/#13" fragments is lost, the SalI cleavage sites between the SalI J and C and
      between SalI F and J fragments are lost, and the SalI E fragment is abnormally
      large (SaE(L) variation). The RFLP and geographic distribution of one more HSV-1
      RFLP variant, BgO(L), were comparatively analyzed. The BglII cleavage site
      between the BglII O and Q/#13 fragments is lost in BgOL. BgO(L) clinical isolates
      were not associated with any of the SaCFJ(M), SaE(L), SaGH(M), or KpM(S)
      variations, whereas one-fourth of the non-BgO(L):non-BgK(L) isolates was
      associated with SaCFJ(M) and SaGH(M), indicating that BgK(L) and BgO(L) are
      distant in terms of diversification. BgO(L) is distributed highly in the
      northeastern region and the southwestern island of Kyushu but is rare between the
      two regions in Japan, in a remarkable contrast to BgK(L). These are the first
      epidemiologic data to show contrasting geographic distribution profiles of two
      HSV-1 variants and suggest the gradual dispersion and replacement of HSV-1
      variants.

PMID- 17215350
TI  - Arabidopsis systemic immunity uses conserved defense signaling pathways and is
      mediated by jasmonates.
AB  - In the absence of adaptive immunity displayed by animals, plants respond locally
      to biotic challenge via inducible basal defense networks activated through
      recognition and response to conserved pathogen-associated molecular patterns. In
      addition, immunity can be induced in tissues remote from infection sites by
      systemic acquired resistance (SAR), initiated after gene-for-gene recognition
      between plant resistance proteins and microbial effectors. The nature of the
      mobile signal and remotely activated networks responsible for establishing SAR
      remain unclear. Salicylic acid (SA) participates in the local and systemic
      response, but SAR does not require long-distance translocation of SA. Here, we
      show that, despite the absence of pathogen-associated molecular pattern contact,
      systemically responding leaves rapidly activate a SAR transcriptional signature
      with strong similarity to local basal defense. We present several lines of
      evidence that suggest jasmonates are central to systemic defense, possibly acting
      as the initiating signal for classic SAR. Jasmonic acid (JA), but not SA, rapidly
      accumulates in phloem exudates of leaves challenged with an avirulent strain of
      Pseudomonas syringae. In systemically responding leaves, transcripts associated
      with jasmonate biosynthesis are up-regulated within 4 h, and JA increases
      transiently. SAR can be mimicked by foliar JA application and is abrogated in
      mutants impaired in jasmonate synthesis or response. We conclude that jasmonate
      signaling appears to mediate long-distance information transmission. Moreover,
      the systemic transcriptional response shares extraordinary overlap with local
      herbivory and wounding responses, indicating that jasmonates may be pivotal to an
      evolutionarily conserved signaling network that decodes multiple abiotic and
      biotic stress signals.

PMID- 17215351
TI  - Differential distribution of NCX1 contributes to spine-dendrite
      compartmentalization in CA1 pyramidal cells.
AB  - Compartmentalization of Ca(2+) between dendritic spines and shafts is governed by
      diffusion barriers and a range of Ca(2+) extrusion mechanisms. The distinct
      contribution of different Ca(2+) clearance systems to Ca(2+) compartmentalization
      in dendritic spines versus shafts remains elusive. We applied a combination of
      ultrastructural and functional imaging methods to assess the subcellular
      distribution and role of NCX1 in rat CA1 pyramidal cells. Quantitative electron
      microscopic analysis of preembedding immunogold reactions revealed uniform
      densities of NCX1 along the shafts of apical and basal dendrites, but densities
      in dendritic shafts were approximately seven times higher than in dendritic
      spines. In line with these results, two-photon imaging of synaptically activated
      Ca(2+) transients during NCX blockade showed preferential action localized to the
      dendritic shafts for NCXs in regulating spine-dendrite coupling.

PMID- 17215352
TI  - Effects of lengthscales and attractions on the collapse of hydrophobic polymers
      in water.
AB  - We present results from extensive molecular dynamics simulations of collapse
      transitions of hydrophobic polymers in explicit water focused on understanding
      effects of lengthscale of the hydrophobic surface and of attractive interactions
      on folding. Hydrophobic polymers display parabolic, protein-like, temperature
      dependent free energy of unfolding. Folded states of small attractive polymers
      are marginally stable at 300 K and can be unfolded by heating or cooling.
      Increasing the lengthscale or decreasing the polymer-water attractions stabilizes
      folded states significantly, the former dominated by the hydration contribution.
      That hydration contribution can be described by the surface tension model, DeltaG
      = gamma(T)DeltaA, where the surface tension, gamma, is lengthscale-dependent and
      decreases monotonically with temperature. The resulting variation of the
      hydration entropy with polymer lengthscale is consistent with theoretical
      predictions of Huang and Chandler [Huang DM, Chandler D (2000) Proc Natl Acad Sci
      USA 97:] that explain the blurring of entropy convergence observed in protein
      folding thermodynamics. Analysis of water structure shows that the polymer-water
      hydrophobic interface is soft and weakly dewetted, and is characterized by
      enhanced interfacial density fluctuations. Formation of this interface, which
      induces polymer folding, is strongly opposed by enthalpy and favored by entropy,
      similar to the vapor-liquid interface.

PMID- 17215353
TI  - Soil nutrients influence spatial distributions of tropical tree species.
AB  - The importance of niche vs. neutral assembly mechanisms in structuring tropical
      tree communities remains an important unsettled question in community ecology
      [Bell G (2005) Ecology 86:1757-1770]. There is ample evidence that species
      distributions are determined by soils and habitat factors at landscape (<10(4)
      km(2)) and regional scales. At local scales (<1 km(2)), however, habitat factors
      and species distributions show comparable spatial aggregation, making it
      difficult to disentangle the importance of niche and dispersal processes. In this
      article, we test soil resource-based niche assembly at a local scale, using
      species and soil nutrient distributions obtained at high spatial resolution in
      three diverse neotropical forest plots in Colombia (La Planada), Ecuador
      (Yasuni), and Panama (Barro Colorado Island). Using spatial distribution maps of
      >0.5 million individual trees of 1,400 species and 10 essential plant nutrients,
      we used Monte Carlo simulations of species distributions to test plant-soil
      associations against null expectations based on dispersal assembly. We found that
      the spatial distributions of 36-51% of tree species at these sites show strong
      associations to soil nutrient distributions. Neutral dispersal assembly cannot
      account for these plant-soil associations or the observed niche breadths of these
      species. These results indicate that belowground resource availability plays an
      important role in the assembly of tropical tree communities at local scales and
      provide the basis for future investigations on the mechanisms of resource
      competition among tropical tree species.

PMID- 17215354
TI  - A precise packing sequence for self-assembled convex structures.
AB  - Molecular simulations of the self-assembly of cone-shaped particles with
      specific, attractive interactions are performed. Upon cooling from random initial
      conditions, we find that the cones self-assemble into clusters and that clusters
      comprised of particular numbers of cones (e.g., 4-17, 20, 27, 32, and 42) have a
      unique and precisely packed structure that is robust over a range of cone angles.
      These precise clusters form a sequence of structures at specific cluster sizes (a
      "precise packing sequence") that for small sizes is identical to that observed in
      evaporation-driven assembly of colloidal spheres. We further show that this
      sequence is reproduced and extended in simulations of two simple models of
      spheres self-assembling from random initial conditions subject to convexity
      constraints, including an initial spherical convexity constraint for moderate-
      and large-sized clusters. This sequence contains six of the most common virus
      capsid structures obtained in vivo, including large chiral clusters and a cluster
      that may correspond to several non-icosahedral, spherical virus capsids obtained
      in vivo. Our findings suggest that this precise packing sequence results from
      free energy minimization subject to convexity constraints and is applicable to a
      broad range of assembly processes.

PMID- 17215355
TI  - Neutron scattering reveals extremely slow cell water in a Dead Sea organism.
AB  - Intracellular water dynamics in Haloarcula marismortui, an extremely halophilic
      organism originally isolated from the Dead Sea, was studied by neutron
      scattering. The water in centrifuged cell pellets was examined by means of two
      spectrometers, IN6 and IN16, sensitive to motions with time scales of 10 ps and 1
      ns, respectively. From IN6 data, a translational diffusion constant of 1.3 x 10(
      5) cm(2) s(-1) was determined at 285 K. This value is close to that found
      previously for other cells and close to that for bulk water, as well as that of
      the water in the 3.5 M NaCl solution bathing the cells. A very slow water
      component was discovered from the IN16 data. At 285 K the water-protons of this
      component displays a residence time of 411 ps (compared with a few ps in bulk
      water). At 300 K, the residence time dropped to 243 ps and was associated with a
      translational diffusion of 9.3 x 10(-8) cm(2) s(-1), or 250 times lower than that
      of bulk water. This slow water accounts for approximately 76% of cell water in H.
      marismortui. No such water was found in Escherichia coli measured on BSS, a
      neutron spectrometer with properties similar to those of IN16. It is hypothesized
      that the slow mobility of a large part of H. marismortui cell water indicates a
      specific water structure responsible for the large amounts of K(+) bound within
      these extremophile cells.

PMID- 17215356
TI  - Serum response factor and myocardin mediate arterial hypercontractility and
      cerebral blood flow dysregulation in Alzheimer's phenotype.
AB  - Cerebral angiopathy contributes to cognitive decline and dementia in Alzheimer's
      disease (AD) through cerebral blood flow (CBF) reductions and dysregulation. We
      report vascular smooth muscle cells (VSMC) in small pial and intracerebral
      arteries, which are critical for CBF regulation, express in AD high levels of
      serum response factor (SRF) and myocardin (MYOCD), two interacting transcription
      factors that orchestrate a VSMC-differentiated phenotype. Consistent with this
      finding, AD VSMC overexpressed several SRF-MYOCD-regulated contractile proteins
      and exhibited a hypercontractile phenotype. MYOCD overexpression in control human
      cerebral VSMC induced an AD-like hypercontractile phenotype and diminished both
      endothelial-dependent and -independent relaxation in the mouse aorta ex vivo. In
      contrast, silencing SRF normalized contractile protein content and reversed a
      hypercontractile phenotype in AD VSMC. MYOCD in vivo gene transfer to mouse pial
      arteries increased contractile protein content and diminished CBF responses
      produced by brain activation in wild-type mice and in two AD models, the
      Dutch/Iowa/Swedish triple mutant human amyloid beta-peptide (Abeta)-precursor
      protein (APP)- expressing mice and APPsw(+/-) mice. Silencing Srf had the
      opposite effect. Expression of SRF did not change in VSMC subjected to
      Alzheimer's neurotoxin, Abeta. Thus, SRF-MYOCD overexpression in small cerebral
      arteries appears to initiate independently of Abeta a pathogenic pathway
      mediating arterial hypercontractility and CBF dysregulation, which are associated
      with Alzheimer's dementia.

PMID- 17215357
TI  - Rhomboid protease AarA mediates quorum-sensing in Providencia stuartii by
      activating TatA of the twin-arginine translocase.
AB  - The Providencia stuartii AarA protein is a member of the rhomboid family of
      intramembrane serine proteases and is required for the production of an unknown
      quorum-sensing molecule. In a screen to identify rhomboid-encoding genes from
      Proteus mirabilis, tatA was identified as a multicopy suppressor and restored
      extracellular signal production as well as complementing all other phenotypes of
      a Prov. stuartii aarA mutant. TatA is a component of the twin-arginine
      translocase (Tat) protein secretion pathway and likely forms a secretion pore. By
      contrast, the native tatA gene of Prov. stuartii in multicopy did not suppress an
      aarA mutation. We find that TatA in Prov. stuartii has a short N-terminal
      extension that was atypical of TatA proteins from most other bacteria. This
      extension was proteolytically removed by AarA both in vivo and in vitro. A Prov.
      stuartii TatA protein missing the first 7 aa restored the ability to rescue the
      aarA-dependent phenotypes. To verify that loss of the Tat system was responsible
      for the various phenotypes exhibited by an aarA mutant, a tatC-null allele was
      constructed. The tatC mutant exhibited the same phenotypes as an aarA mutant and
      was epistatic to aarA. These data provide a molecular explanation for the
      requirement of AarA in quorum-sensing and uncover a function for the Tat protein
      export system in the production of secreted signaling molecules. Finally, TatA
      represents a validated natural substrate for a prokaryotic rhomboid protease.

PMID- 17215358
TI  - Flat and sigmoidally curved contact zones in vesicle-vesicle adhesion.
AB  - Using the membrane-bending elasticity theory and a simple effective model of
      adhesion, we study the morphology of lipid vesicle doublets. In the weak adhesion
      regime, we find flat-contact axisymmetric doublets, whereas at large adhesion
      strengths, the vesicle aggregates are nonaxisymmetric and characterized by a
      sigmoidally curved, S-shaped contact zone with a single invagination and a
      complementary evagination on each vesicle. The sigmoid-contact doublets agree
      very well with the experimentally observed shapes of erythrocyte aggregates. Our
      results show that in identical vesicles with large to moderate surface-to-volume
      ratio, the sigmoid-contact shape is the only bound morphology. We also discuss
      the role of sigmoid contacts in the formation of multicellular aggregates such as
      erythrocyte rouleaux.

PMID- 17215359
TI  - A comprehensive transposon mutant library of Francisella novicida, a bioweapon
      surrogate.
AB  - Francisella tularensis, the causative agent of tularemia, is one of the most
      infectious bacterial pathogens known and is a category A select agent. We created
      a sequence-defined, near-saturation transposon mutant library of F. tularensis
      novicida, a subspecies that causes a tularemia-like disease in rodents. The
      library consists of 16,508 unique insertions, an average of >9 insertions per
      gene, which is a coverage nearly twice that of the greatest previously achieved
      for any bacterial species. Insertions were recovered in 84% (1,490) of the
      predicted genes. To achieve high coverage, it was necessary to construct
      transposons carrying an endogenous Francisella promoter to drive expression of
      antibiotic resistance. An analysis of genes lacking (or with few) insertions
      identified nearly 400 candidate essential genes, most of which are likely to be
      required for growth on rich medium and which represent potential therapeutic
      targets. To facilitate genome-scale screening using the mutant collection, we
      assembled a sublibrary made up of two purified mutants per gene. The library
      provides a resource for virtually complete identification of genes involved in
      virulence and other nonessential processes.

PMID- 17215360
TI  - Detecting and assessing macrophages in vivo to evaluate atherosclerosis
      noninvasively using molecular MRI.
AB  - We investigated the ability of targeted immunomicelles to detect and assess
      macrophages in atherosclerotic plaque using MRI in vivo. There is a large
      clinical need for a noninvasive tool to assess atherosclerosis from a molecular
      and cellular standpoint. Macrophages play a central role in atherosclerosis and
      are associated with plaques vulnerable to rupture. Therefore, macrophage
      scavenger receptor (MSR) was chosen as a target for molecular MRI. MSR-targeted
      immunomicelles, micelles, and gadolinium-diethyltriaminepentaacetic acid (DTPA)
      were tested in ApoE-/- and WT mice by using in vivo MRI. Confocal laser-scanning
      microscopy colocalization, macrophage immunostaining and MRI correlation,
      competitive inhibition, and various other analyses were performed. In vivo MRI
      revealed that at 24 h postinjection, immunomicelles provided a 79% increase in
      signal intensity of atherosclerotic aortas in ApoE-/- mice compared with only 34%
      using untargeted micelles and no enhancement using gadolinium-DTPA. Confocal
      laser-scanning microscopy revealed colocalization between fluorescent
      immunomicelles and macrophages in plaques. There was a strong correlation between
      macrophage content in atherosclerotic plaques and the matched in vivo MRI results
      as measured by the percent normalized enhancement ratio. Monoclonal antibodies to
      MSR were able to significantly hinder immunomicelles from providing contrast
      enhancement of atherosclerotic vessels in vivo. Immunomicelles provided excellent
      validated in vivo enhancement of atherosclerotic plaques. The enhancement seen is
      related to the macrophage content of the atherosclerotic vessel areas imaged.
      Immunomicelles may aid in the detection of high macrophage content associated
      with plaques vulnerable to rupture.

PMID- 17215361
TI  - Structure of the light-harvesting bacteriochlorophyll c assembly in chlorosomes
      from Chlorobium limicola determined by solid-state NMR.
AB  - We have determined the atomic structure of the bacteriochlorophyll c (BChl c)
      assembly in a huge light-harvesting organelle, the chlorosome of green
      photosynthetic bacteria, by solid-state NMR. Previous electron microscopic and
      spectroscopic studies indicated that chlorosomes have a cylindrical architecture
      with a diameter of approximately 10 nm consisting of layered BChl molecules.
      Assembly structures in huge noncrystalline chlorosomes have been proposed based
      mainly on structure-dependent chemical shifts and a few distances acquired by
      solid-state NMR, but those studies did not provide a definite structure. Our
      approach is based on (13)C dipolar spin-diffusion solid-state NMR of uniformly
      (13)C-labeled chlorosomes under magic-angle spinning. Approximately 90
      intermolecular C C distances were obtained by simultaneous assignment of distance
      correlations and structure optimization preceded by polarization-transfer matrix
      analysis. It was determined from the approximately 90 intermolecular distances
      that BChl c molecules form piggyback-dimer-based parallel layers. This finding
      rules out the well known monomer-based structures. A molecular model of the
      cylinder in the chlorosome was built by using this structure. It provided
      insights into the mechanisms of efficient light harvesting and excitation
      transfer to the reaction centers. This work constitutes an important advance in
      the structure determination of huge intact systems that cannot be crystallized.

PMID- 17215363
TI  - Improved evolutionary optimization from genetically adaptive multimethod search.
AB  - In the last few decades, evolutionary algorithms have emerged as a revolutionary
      approach for solving search and optimization problems involving multiple
      conflicting objectives. Beyond their ability to search intractably large spaces
      for multiple solutions, these algorithms are able to maintain a diverse
      population of solutions and exploit similarities of solutions by recombination.
      However, existing theory and numerical experiments have demonstrated that it is
      impossible to develop a single algorithm for population evolution that is always
      efficient for a diverse set of optimization problems. Here we show that
      significant improvements in the efficiency of evolutionary search can be achieved
      by running multiple optimization algorithms simultaneously using new concepts of
      global information sharing and genetically adaptive offspring creation. We call
      this approach a multialgorithm, genetically adaptive multiobjective, or AMALGAM,
      method, to evoke the image of a procedure that merges the strengths of different
      optimization algorithms. Benchmark results using a set of well known
      multiobjective test problems show that AMALGAM approaches a factor of 10
      improvement over current optimization algorithms for the more complex, higher
      dimensional problems. The AMALGAM method provides new opportunities for solving
      previously intractable optimization problems.

PMID- 17215362
TI  - Profile of J. Woodland Hastings.

PMID- 17215364
TI  - Requirement of the C3HC4 zinc RING finger of the Arabidopsis PEX10 for
      photorespiration and leaf peroxisome contact with chloroplasts.
AB  - Plant peroxisomes perform multiple vital metabolic processes including lipid
      mobilization in oil-storing seeds, photorespiration, and hormone biosynthesis.
      Peroxisome biogenesis requires the function of peroxin (PEX) proteins, including
      PEX10, a C(3)HC(4) Zn RING finger peroxisomal membrane protein. Loss of function
      of PEX10 causes embryo lethality at the heart stage. We investigated the function
      of PEX10 with conditional sublethal mutants. Four T-DNA insertion lines
      expressing pex10 with a dysfunctional RING finger were created in an Arabidopsis
      WT background (DeltaZn plants). They could be normalized by growth in an
      atmosphere of high CO(2) partial pressure, indicating a defect in
      photorespiration. beta-Oxidation in mutant glyoxysomes was not affected. However,
      an abnormal accumulation of the photorespiratory metabolite glyoxylate, a lowered
      content of carotenoids and chlorophyll a and b, and a decreased quantum yield of
      photosystem II were detected under normal atmosphere, suggesting impaired leaf
      peroxisomes. Light and transmission electron microscopy demonstrated leaf
      peroxisomes of the DeltaZn plants to be more numerous, multilobed, clustered, and
      not appressed to the chloroplast envelope as in WT. We suggest that inactivation
      of the RING finger domain in PEX10 has eliminated protein interaction required
      for attachment of peroxisomes to chloroplasts and movement of metabolites between
      peroxisomes and chloroplasts.

PMID- 17215366
TI  - Mitochondrial dysfunction in the pathogenesis of Ullrich congenital muscular
      dystrophy and prospective therapy with cyclosporins.
AB  - Ullrich congenital muscular dystrophy is a severe genetically and clinically
      heterogeneous muscle disorder linked to collagen VI deficiency. The pathogenesis
      of the disease is unknown. To assess the potential role of mitochondrial
      dysfunction in the onset of muscle fiber death in this form of dystrophy, we
      studied biopsies and myoblast cultures obtained from patients with different
      genetic defects of collagen VI and variable clinical presentations of the
      disease. We identified a latent mitochondrial dysfunction in myoblasts from
      patients with Ullrich congenital muscular dystrophy that matched an increased
      occurrence of spontaneous apoptosis. Unlike those in myoblasts from healthy
      donors, mitochondria in cells from patients depolarized upon addition of
      oligomycin and displayed ultrastructural alterations that were worsened by
      treatment with oligomycin. The increased apoptosis, the ultrastructural defects,
      and the anomalous response to oligomycin could be normalized by Ca(2+) chelators,
      by plating cells on collagen VI, and by treatment with cyclosporin A or with the
      specific cyclophilin inhibitor methylAla(3)ethylVal(4)-cyclosporin, which does
      not affect calcineurin activity. Here we demonstrate that mitochondrial
      dysfunction plays an important role in muscle cell wasting in Ullrich congenital
      muscular dystrophy. This study represents an essential step toward a
      pharmacological therapy of Ullrich congenital muscular dystrophy with cyclosporin
      A and methylAla(3)ethylVal(4) cyclosporin.

PMID- 17215365
TI  - Biomimetic amplification of nanoparticle homing to tumors.
AB  - Nanoparticle-based diagnostics and therapeutics hold great promise because
      multiple functions can be built into the particles. One such function is an
      ability to home to specific sites in the body. We describe here biomimetic
      particles that not only home to tumors, but also amplify their own homing. The
      system is based on a peptide that recognizes clotted plasma proteins and
      selectively homes to tumors, where it binds to vessel walls and tumor stroma.
      Iron oxide nanoparticles and liposomes coated with this tumor-homing peptide
      accumulate in tumor vessels, where they induce additional local clotting, thereby
      producing new binding sites for more particles. The system mimics platelets,
      which also circulate freely but accumulate at a diseased site and amplify their
      own accumulation at that site. The self-amplifying homing is a novel function for
      nanoparticles. The clotting-based amplification greatly enhances tumor imaging,
      and the addition of a drug carrier function to the particles is envisioned.

PMID- 17215367
TI  - Polycomb-like genes are necessary for specification of dopaminergic and
      serotonergic neurons in Caenorhabditis elegans.
AB  - The molecular mechanisms underlying the formation of neurons with defined
      neurotransmitters are not well understood. In this study, we demonstrate that the
      PcG-like genes in Caenorhabditis elegans, sop-2 and sor-3, regulate the formation
      of dopaminergic and serotonergic neurons and several other neuronal properties.
      sor-3 encodes a novel protein containing an MBT repeat, a domain that contains
      histone-binding activity and is present in PcG proteins SCM and Sfmbt in other
      organisms. We further show that mutations in sor-3 lead to ectopic expression of
      Hox genes and cause homeotic transformations. Specification of certain neuronal
      identities by these PcG-like genes appears to involve regulation of non-Hox gene
      targets. Our studies revealed that the PcG-like genes are crucial for
      coordinately regulating the expression of discrete aspects of neuronal identities
      in C. elegans.

PMID- 17215368
TI  - Intramolecular interaction in the tail of Acanthamoeba myosin IC between the SH3
      domain and a putative pleckstrin homology domain.
AB  - The 466-aa tail of the heavy chain of Acanthamoeba myosin IC (AMIC) comprises an
      N-terminal 220-residue basic region (BR) followed by a 56-residue Gly/Pro/Ala
      rich region (GPA1), a 55-residue Src homology 3 (SH3) domain, and a C-terminal
      135-residue Gly/Pro/Ala-rich region (GPA2). Cryo-electron microscopy of AMIC had
      shown previously that the AMIC tail is folded back on itself, suggesting the
      possibility of interactions between its N- and C-terminal regions. We now show
      specific differences between the NMR spectrum of bacterially expressed full
      length tail and the sum of the spectra of individually expressed BR and GPA1-SH3
      GPA2 (GSG) regions. These results are indicative of interactions between the two
      subdomains in the full-length tail. From the NMR data, we could assign many of
      the residues in BR and GSG that are involved in these interactions. By combining
      homology modeling with the NMR data, we identify a putative pleckstrin homology
      (PH) domain within BR, and show that the PH domain interacts with the SH3 domain.

PMID- 17215369
TI  - Molecular markers of early Parkinson's disease based on gene expression in blood.
AB  - Parkinson's disease (PD) progresses relentlessly and affects five million people
      worldwide. Laboratory tests for PD are critically needed for developing
      treatments designed to slow or prevent progression of the disease. We performed a
      transcriptome-wide scan in 105 individuals to interrogate the molecular processes
      perturbed in cellular blood of patients with early-stage PD. The molecular
      multigene marker here identified is associated with risk of PD in 66 samples of
      the training set comprising healthy and disease controls [third tertile cross
      validated odds ratio of 5.7 (P for trend 0.005)]. It is further validated in 39
      independent test samples [third tertile odds ratio of 5.1 (P for trend 0.04)].
      Insights into disease-linked processes detectable in peripheral blood are offered
      by 22 unique genes differentially expressed in patients with PD versus healthy
      individuals. These include the co-chaperone ST13, which stabilizes heat-shock
      protein 70, a modifier of alpha-synuclein misfolding and toxicity. ST13 messenger
      RNA copies are lower in patients with PD (mean +/- SE 0.59 +/- 0.05) than in
      controls (0.96 +/- 0.09) (P = 0.002) in two independent populations. Thus, gene
      expression signals measured in blood can facilitate the development of biomarkers
      for PD.

PMID- 17215370
TI  - Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo.
AB  - Faster aging is predicted in more active tissues and animals because of greater
      reactive oxygen species generation. Yet age-related cell loss is greater in less
      active cell types, such as type II muscle fibers. Mitochondrial uncoupling has
      been proposed as a mechanism that reduces reactive oxygen species production and
      could account for this paradox between longevity and activity. We distinguished
      these hypotheses by using innovative optical and magnetic resonance spectroscopic
      methods applied to noninvasively measured ATP synthesis and O(2) uptake in vivo
      in human muscle. Here we show that mitochondrial function is unchanged with age
      in mildly uncoupled tibialis anterior muscle (75% type I) despite a high
      respiratory rate in adults. In contrast, substantial uncoupling and loss of
      cellular [ATP] indicative of mitochondrial dysfunction with age was found in the
      lower respiring and well coupled first dorsal interosseus (43-50% type II) of the
      same subjects. These results reject respiration rate as the sole factor impacting
      the tempo of cellular aging. Instead, they support mild uncoupling as a mechanism
      protecting mitochondrial function and contributing to the paradoxical longevity
      of the most active muscle fibers.

PMID- 17215371
TI  - Mechanism of methanol oxidation by quinoprotein methanol dehydrogenase.
AB  - At neutral pH, oxidation of CH(3)OH --> CH(2)O by an o-quinone requires general
      base catalysis and the reaction is endothermic. The active-site -CO(2)(-) groups
      of Glu-171 and Asp-297 (Glu-171-CO(2)(-) and Asp-297-CO(2)(-)) have been
      considered as the required general base catalysts in the bacterial o-quinoprotein
      methanol dehydrogenase (MDH) reaction. Based on quantum mechanics/molecular
      mechanics (QM/MM) calculations, the free energy for MeOH reduction of o-PQQ when
      MeOH is hydrogen bonded to Glu-171-CO(2)(-) and the crystal water (Wat1) is
      hydrogen bonded to Asp-297-CO(2)(-) is DeltaG++ = 11.7 kcal/mol, which is
      comparable with the experimental value of 8.5 kcal/mol. The calculated DeltaG++
      when MeOH is hydrogen bonded to Asp-297-CO(2)(-) is >50 kcal/mol. The Asp-297
      CO(2)(-)...Wat1 complex is very stable. Molecular dynamics (MD) simulations on
      MDH.PQQ.Wat1 complex in TIP3P water for 5 ns does not result in interchange of
      Asp-297-CO(2)(-) bound Wat1 for a solvent water. Starting with Wat1 removed and
      MeOH hydrogen bonded to Asp-297-CO(2)(-), we find that MeOH returns to be
      hydrogen bonded to Glu-171-CO(2)(-) and Asp-297-CO(2)(-) coordinates to Ca(2+)
      during 3 ns simulation. The Asp-297-CO(2)(-)...Wat1 of reactant complex does play
      a crucial role in catalysis. By QM/MM calculation DeltaG++ = 1.1 kcal/mol for Asp
      297-CO(2)(-) general-base catalysis of Wat1 hydration of the immediate CH(2)==O
      product --> CH(2)(OH)(2). By this means, the endothermic oxidation-reduction
      reaction is pulled such that the overall conversion of MeOH to CH(2)(OH)(2) is
      exothermic.

PMID- 17215372
TI  - A quantitative, theoretical framework for understanding mammalian sleep.
AB  - Sleep is one of the most noticeable and widespread phenomena occurring in
      multicellular animals. Nevertheless, no consensus for a theory of its origins has
      emerged. In particular, no explicit, quantitative theory exists that elucidates
      or distinguishes between the myriad hypotheses proposed for sleep. Here, we
      develop a general, quantitative theory for mammalian sleep that relates many of
      its fundamental parameters to metabolic rate and body size. Several mechanisms
      suggested for the function of sleep can be placed in this framework, e.g.,
      cellular repair of damage caused by metabolic processes as well as cortical
      reorganization to process sensory input. Our theory leads to predictions for
      sleep time, sleep cycle time, and rapid eye movement time as functions of body
      and brain mass, and it explains, for example, why mice sleep approximately 14
      hours per day relative to the 3.5 hours per day that elephants sleep. Data for 96
      species of mammals, spanning six orders of magnitude in body size, are consistent
      with these predictions and provide strong evidence that time scales for sleep are
      set by the brain's, not the whole-body, metabolic rate.

PMID- 17215373
TI  - Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1.
AB  - Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive
      disorder caused by mutations in the autoimmune regulator (AIRE) gene. High titer
      autoantibodies (Aabs) toward intracellular enzymes are a hallmark for APS1 and
      serve as diagnostic markers and predictors for disease manifestations. In this
      study, we aimed to identify pituitary autoantigens in patients with APS1. A
      pituitary cDNA expression library was screened with APS1 sera and a tudor domain
      containing protein 6 (TDRD6) cDNA clone was isolated. Positive immunoreactivity
      against in vitro translated TDRD6 fragments was shown in 42/86 (49%) APS1
      patients but not in patients with other autoimmune diseases or in healthy
      controls. By using immunohistochemistry, sera from 3/6 APS1 patients with growth
      hormone (GH) deficiency showed immunostaining of a small number of guinea pig
      anterior pituitary cells, and 40-50% of these cells were GH-positive. No such
      immunostaining was seen with sera from healthy controls. The APS1 Aab-positive,
      GH-negative cells may represent a novel subpopulation of anterior pituitary
      cells. In addition, 4/6 patient sera showed staining of a fiber-plexus in the
      pituitary intermediate lobe recognizing enzymes of monoamine and GABA synthesis.
      Thus, we have identified TDRD6 as a major autoantigen in APS1 patients and shown
      that several sera from GH-deficient patients stain specific cell populations and
      nerves in the pituitary gland.

PMID- 17215374
TI  - DNA folding and melting observed in real time redefine the energy landscape.
AB  - We report real-time observations of the folding and melting of DNA by probing two
      active sites of a hairpin structure, the bases and the stem end, and using an
      ultrafast T-jump. Studies at different initial temperatures (before, during, and
      after melting) provide the time scale of water heating (<20 ps), single-strand
      destacking (700 ps to 2 ns), and hairpin destacking (microseconds and longer) in
      solutions of various ionic strengths and pH values. The behavior of transient
      changes gives direct evidence to the existence of intermediate collapsed
      structures, labile in destacking but compact in nature, and indicates that
      melting is not a two-state process. We propose a landscape that is defined by
      these nucleation structures and destacking for efficient folding and melting.

PMID- 17215376
TI  - A compensation election for binary social choice.
AB  - We report experimental results examining the properties of a bidding mechanism,
      the "Compensation Election," which is designed to implement a simple binary
      choice between two options. We may think of the group decision problem as a
      choice between a new rule and the status quo. The rule and the status quo are
      each common outcomes that apply across all individuals, but the value or cost
      that they induce on each individual differs according to each individual's
      circumstances: some gain, some lose, and others are unaffected by a change to the
      new from the old. Rather than casting votes, each subject submits a bid
      reflecting his willingness to pay to induce the group to select one option and
      the amount he wishes to be paid if the alternative option is selected. The
      Compensation Election chooses the option that receives the highest sum of bids.
      We find that, although the Compensation Election allows subjects to strategically
      bid above their value (or even for the option they do not prefer), such behavior
      is not the norm. We also find that subjects' bids more truthfully reveal their
      values when there are more bidders in the election.

PMID- 17215375
TI  - A functional SNP of interferon-gamma gene is important for interferon-alpha
      induced and spontaneous recovery from hepatitis C virus infection.
AB  - Cytokine polymorphisms are associated with disease outcome and interferon (IFN)
      treatment response in hepatitis C virus (HCV) infection. We genotyped eight SNPs
      spanning the entire IFN-gamma gene in two cohorts and assessed the association
      between those polymorphisms and treatment response or spontaneous viral
      clearance. The first cohort was composed of 284 chronically HCV-infected patients
      who had received IFN-alpha-based therapy and the second was 251 i.v. drug users
      who had either spontaneously cleared HCV or become chronically infected. A SNP
      variant located in the proximal IFN-gamma promoter region next to the binding
      motif of heat shock transcription factor (HSF), -764G, was significantly
      associated with sustained virological response [P = 0.01, odds ratio (OR) = 2.66
      [corrected] (confidence interval 1.3-5.6)[corrected]]. The association was
      independently significant in multiple logistic regression (P = 0.04) along with
      race, viral titer, and genotype. This variant was also significantly associated
      with spontaneous recovery [P = 0.04, OR = 3.51 (1.0-12.5)] in the second cohort.
      Functional analyses show that the G allele confers a two- to three-fold higher
      promoter activity and stronger binding affinity to HSF1 than the C allele. Our
      study suggests that the IFN-gamma promoter SNP -764G/C is functionally important
      in determining viral clearance and treatment response in HCV-infected patients
      and may be used as a genetic marker to predict sustained virological response in
      HCV-infected patients.

PMID- 17215377
TI  - A critical role for peptidoglycan N-deacetylation in Listeria evasion from the
      host innate immune system.
AB  - Listeria monocytogenes is a human intracellular pathogen that is able to survive
      in the gastrointestinal environment and replicate in macrophages, thus bypassing
      the early innate immune defenses. Peptidoglycan (PG) is an essential component of
      the bacterial cell wall readily exposed to the host and, thus, an important
      target for the innate immune system. Characterization of the PG from L.
      monocytogenes demonstrated deacetylation of N-acetylglucosamine residues. We
      identified a PG N-deacetylase gene, pgdA, in L. monocytogenes genome sequence.
      Inactivation of pgdA revealed the key role of this PG modification in bacterial
      virulence because the mutant was extremely sensitive to the bacteriolytic
      activity of lysozyme, and growth was severely impaired after oral and i.v.
      inoculations. Within macrophage vacuoles, the mutant was rapidly destroyed and
      induced a massive IFN-beta response in a TLR2 and Nod1-dependent manner.
      Together, these results reveal that PG N-deacetylation is a highly efficient
      mechanism used by Listeria to evade innate host defenses. The presence of
      deacetylase genes in other pathogenic bacteria indicates that PG N-deacetylation
      could be a general mechanism used by bacteria to evade the host innate immune
      system.

PMID- 17215378
TI  - A G protein/cAMP signal cascade is required for axonal convergence into olfactory
      glomeruli.
AB  - The mammalian odorant receptors (ORs) comprise a large family of G protein
      coupled receptors that are critical determinants of both the odorant response
      profile and the axonal identity of the olfactory sensory neurons in which they
      are expressed. Although the pathway by which ORs activate odor transduction is
      well established, the mechanism by which they direct axons into proper glomerular
      relationships remains unknown. We have developed a gain-of-function approach by
      using injection of retroviral vectors into the embryonic olfactory epithelium to
      study the ORs' contribution to axon guidance. By ectopically expressing ORs, we
      demonstrate that functional OR proteins induce axonal coalescence. Furthermore,
      ectopic expression of Galpha mutants reveals that activation of the signal
      transduction cascade is sufficient to cause axonal convergence into glomeruli.
      Analysis of Galpha subunit expression indicates that development and odorant
      transduction use separate transduction pathways. Last, we establish that the
      generation of cAMP through adenylyl cyclase 3 is necessary to establish proper
      axonal identity. Our data point to a model in which axonal sorting is
      accomplished by OR stimulation of cAMP production by coupling to Galphas.

PMID- 17215379
TI  - Birth weight and subsequent risk of type 2 diabetes: a meta-analysis.
AB  - The "small baby syndrome hypothesis" suggests that an inverse linear relation
      exists between birth weight and risk of type 2 diabetes. The authors conducted a
      meta-analysis to examine this association. They included studies that reported
      odds ratios and 95% confidence intervals (or data with which to calculate them)
      for the association of type 2 diabetes with birth weight. Fourteen studies
      involving a total of 132,180 persons were identified. Low birth weight (<2,500
      g), as compared with a birth weight of >/=2,500 g, was associated with increased
      risk of type 2 diabetes (odds ratio (OR) = 1.32, 95% confidence interval (CI):
      1.06, 1.64). High birth weight (>4,000 g), as compared with a birth weight of
      </=4,000 g, was associated with increased risk to the same extent (OR = 1.27, 95%
      CI: 1.01, 1.59). Pooled estimates increased further when normal birth weight
      (2,500-4,000 g) was used as the reference category (low birth weight: OR = 1.47,
      95% CI: 1.26, 1.72; high birth weight: OR = 1.36, 95% CI: 1.07, 1.73). Meta
      regression and categorical analyses showed a U-shaped relation between birth
      weight and diabetes risk. These findings indicate that there exists a relation
      between birth weight and later-life risk of type 2 diabetes which is not linearly
      inverse but U-shaped.

PMID- 17215380
TI  - Calcium and vitamin D intake and risk of colorectal cancer: the Multiethnic
      Cohort Study.
AB  - The associations of intakes of calcium and vitamin D with colorectal cancer risk
      were examined in the Multiethnic Cohort Study (Hawaii and Los Angeles,
      California). In 1993-1996, 85,903 men and 105,108 women aged > or =45 years
      completed a quantitative food frequency questionnaire. A total of 2,110 incident
      cases of colorectal cancer (1,138 in men and 972 in women) were identified
      through December 31, 2001. Cox proportional hazards models were used to calculate
      multivariate-adjusted relative risks and 95% confidence intervals. Total calcium
      intake (from foods and supplements) was inversely associated with colorectal
      cancer risk in both men (highest quintile vs. lowest: relative risk (RR) = 0.70,
      95% confidence interval (CI): 0.52, 0.93; p for trend = 0.006) and women (RR =
      0.64, 95% CI: 0.50, 0.83; p for trend = 0.003). The inverse association was also
      seen for total vitamin D intake in men (RR = 0.72, 95% CI: 0.51, 1.00; p for
      trend = 0.03) but not in women. Intake of dairy products was inversely associated
      with colorectal cancer risk, especially among nonusers of supplemental calcium
      (men: RR = 0.77, 95% CI: 0.59, 1.01; women: RR = 0.66, 95% CI: 0.49, 0.89). The
      findings support the hypothesis of protective roles for calcium, vitamin D, and
      dairy products in the risk of colorectal cancer.

PMID- 17215381
TI  - Oral contraceptives, reproductive factors, and risk of colorectal cancer among
      women in a prospective cohort study.
AB  - Previous findings on the associations between oral contraceptive (OC) use and
      reproductive factors and risk of colorectal cancer have been inconclusive. The
      authors evaluated associations of OC use and reproductive factors (including
      parity, age at first birth, age at menarche, and age at menopause) with risk of
      colorectal cancer among women in a large-scale prospective cohort study. The
      analysis included 39,680 participants in the Women's Health Study who had usable
      information on ever use of OCs and potential risk factors for colorectal cancer.
      Relative risks and 95% confidence intervals were estimated from Cox proportional
      hazards regression models. All p values were two-sided. During an average of 11
      years of follow-up (1992-2004), 267 incident cases of colorectal cancer were
      documented. Ever use of OCs was associated with a lower risk of colorectal cancer
      (relative risk = 0.67, 95% confidence interval: 0.50, 0.89). Women who had used
      OCs for 6 months-<3 years had a relative risk of 0.61 (95% confidence interval:
      0.40, 0.94) relative to never users, with little additional decreased risk being
      seen with longer duration of use (p for multivariate trend = 0.09). No
      significant association was observed between reproductive factors and colorectal
      cancer risk. These findings provide some support for a potential role of OCs in
      reducing risk of colorectal cancer.

PMID- 17215382
TI  - Smoking, hypertension, alcohol consumption, and risk of abdominal aortic aneurysm
      in men.
AB  - Despite the known protective association between moderate alcohol consumption and
      ischemic heart disease, little is known about the effects of alcohol consumption
      on abdominal aortic aneurysms (AAA). The authors analyzed prospective, biennially
      updated data for a cohort of 39,352 US men from 1986 to 2002. The association of
      incident AAA diagnosis with alcohol consumption in grams per day was assessed at
      baseline and by using alcohol consumption data updated every 4 years, controlling
      for previously reported cardiovascular risk factors. During 576,374 person-years
      of follow-up, 376 newly diagnosed cases of AAA were demonstrated. After
      adjustment for other risk factors for AAA, including smoking, hypertension, and
      body mass index, alcohol consumption at baseline was independently associated
      with AAA diagnosis (p for trend = 0.03), with a maximum hazard ratio of 1.21 (95%
      confidence interval: 0.78, 1.87) for > or =30.0 g (approximately > or =2 standard
      drinks) of daily alcohol consumption. This association was stronger when the
      updated alcohol consumption data were assessed rather than simply baseline
      exposure (p for trend = 0.02); the hazard ratio for the highest level of intake
      (> or =30.0 g/day) was 1.65 (95% confidence interval: 1.03, 2.64). Small numbers
      limited analyses by beverage type, but liquor demonstrated the strongest positive
      association with AAA.

PMID- 17215383
TI  - Inflammation biomarkers and near-term death in older men.
AB  - Associations of C-reactive protein (CRP) and fibrinogen with death may weaken
      over time. Combining both markers may improve prediction of death in older
      adults. In 5,828 Cardiovascular Health Study participants (United States, 1989
      2000), 383 deaths (183 cardiovascular disease (CVD)) in years 1-3 (early) and 914
      deaths (396 CVD) in years 4-8 (late) occurred. For men, when comparing highest to
      lowest quartiles, hazard ratios for early death were 4.1 (95% confidence interval
      (CI): 2.7, 6.3) for CRP and 4.1 (95% CI: 2.7, 6.4) for fibrinogen in models
      adjusted for CVD risk. For early CVD death, hazard ratios were 4.3 (95% CI: 2.2,
      8.4) and 3.4 (95% CI: 1.8, 6.3), respectively. When comparing men in the highest
      quartiles of both biomarkers with those in the lowest, hazard ratios were 9.6
      (95% CI: 4.3, 21.1) for early death and 13.5 (95% CI: 3.2, 56.5) for early CVD
      death. Associations were weaker for late deaths. For women, CRP (hazard ratio =
      2.3, 95% CI: 1.4, 3.9), but not fibrinogen (hazard ratio = 1.3, 95% CI: 0.8,
      2.2), was associated with early death. Results were similar for CVD death.
      Neither was associated with late deaths. CRP and fibrinogen were more strongly
      associated with death in older men than women and more strongly associated with
      early than late death. Combining both markers may identify older men at greatest
      risk of near-term death.

PMID- 17215384
TI  - Comparison of recordings from microelectrode arrays and single electrodes in the
      visual cortex.

PMID- 17215385
TI  - Bidirectional modulation of transmitter release by calcium channel/syntaxin
      interactions in vivo.
AB  - Protein interactions within the active zone of the nerve terminal are critical
      for regulation of transmitter release. The SNARE protein syntaxin 1A, primarily
      known for important interactions that control vesicle fusion, also interacts with
      presynaptic voltage-gated calcium channels. Based on recordings of calcium
      channel function in vitro, it has been hypothesized that syntaxin 1A-calcium
      channel interactions could alter calcium channel function at synapses. However,
      results at synapses in vitro suggest two potentially opposing roles: enhancement
      of neurotransmitter release by positioning docked vesicles near calcium channels
      and inhibition of calcium channel function by interaction with SNARE proteins. We
      have examined the possibility that these two effects of syntaxin can occur at
      synapses by studying the effects on transmitter release of manipulating syntaxin
      1A-calcium channel interactions at Xenopus tadpole tail neuromuscular synapses in
      vivo. Introduction of synprint peptides, which competitively perturb syntaxin 1A
      calcium channel interactions, decreased quantal content at these synapses and
      increased paired-pulse and tetanic facilitation. In contrast, injecting mRNA for
      mutant (A240V, V244A) syntaxin 1A, which reduces calcium channel modulation but
      not binding in vitro, increased quantal content and decreased paired-pulse and
      tetanic facilitation. Injection of wild-type syntaxin 1A mRNA had no effect. The
      opposing effects of synprint peptides and mutant syntaxin 1A provide in vivo
      support for the hypothesis that these interactions serve both to colocalize
      calcium channels with the release machinery and to modulate the functional state
      of the calcium channel. As such, these two effects of syntaxin on calcium
      channels modulate transmitter release in a bidirectional manner.

PMID- 17215386
TI  - Slow conformational changes of the voltage sensor during the mode shift in
      hyperpolarization-activated cyclic-nucleotide-gated channels.
AB  - Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels are activated
      by hyperpolarizations that cause inward movements of the positive charges in the
      fourth transmembrane domain (S4), which triggers channel opening. If HCN channels
      are held open for prolonged times (>50 ms), HCN channels undergo a mode shift,
      which in sea urchin (spHCN) channels induces a >50 mV shift in the midpoint of
      activation. The mechanism underlying the mode shift is unknown. The mode shift
      could be attributable to conformational changes in the pore domain that stabilize
      the open state of the channel, which would indirectly shift the voltage
      dependence of the channel, or attributable to conformational changes in the
      voltage-sensing domain that stabilize the inward position of S4, thereby directly
      shifting the voltage dependence of the channel. We used voltage-clamp fluorometry
      to detect S4 movements and to correlate S4 movements to the different activation
      steps in spHCN channels. We here show that fluorophores attached to S4 report on
      fluorescence changes during the mode shift, demonstrating that the mode shift is
      not simply attributable to a stabilization of the pore domain but that S4
      undergoes conformational changes during the mode shift. We propose a model in
      which the mode shift is attributable to a slow, lateral movement in S4 that is
      triggered by the initial S4 gating-charge movement and channel opening. The mode
      shift gives rise to a short-term, activity-dependent memory in HCN channels,
      which has been shown previously to be important for the stable rhythmic firing of
      pacemaking neurons and could significantly affect synaptic integration.

PMID- 17215387
TI  - Phosphatidylinositol 3-kinase and Akt nonautonomously promote perineurial glial
      growth in Drosophila peripheral nerves.
AB  - Drosophila peripheral nerves, structured similarly to their mammalian
      counterparts, comprise a layer of motor and sensory axons wrapped by an inner
      peripheral glia (analogous to the mammalian Schwann cell) and an outer
      perineurial glia (analogous to the mammalian perineurium). Growth and
      proliferation within mammalian peripheral nerves are increased by Ras pathway
      activation: loss-of-function mutations in Nf1, which encodes the Ras inhibitor
      neurofibromin, cause the human genetic disorder neurofibromatosis, which is
      characterized by formation of neurofibromas (tumors of peripheral nerves).
      However, the signaling pathways that control nerve growth downstream of Ras
      remain incompletely characterized. Here we show that expression specifically
      within the Drosophila peripheral glia of the constitutively active Ras(V12)
      increases perineurial glial thickness. Using chromosomal loss-of-function
      mutations and transgenes encoding dominant-negative and constitutively active
      proteins, we show that this nonautonomous effect of Ras(V12) is mediated by the
      Ras effector phosphatidylinositol 3-kinase (PI3K) and its downstream kinase Akt.
      We also show that the nonautonomous, growth-promoting effects of activated PI3K
      are suppressed by coexpression within the peripheral glia of FOXO+ (forkhead box
      O) a transcription factor inhibited by Akt-dependent phosphorylation. We suggest
      that Ras-PI3K-Akt activity in the peripheral glia promotes growth of the
      perineurial glia by inhibiting FOXO. In mammalian peripheral nerves, the Schwann
      cell releases several growth factors that affect the proliferative properties of
      neighbors. Some of these factors are oversecreted in Nf1 mutants. Our results
      raise the possibility that neurofibroma formation in individuals with
      neurofibromatosis might result in part from a Ras-PI3K-Akt-dependent inhibition
      of FOXO within Schwann cells.

PMID- 17215388
TI  - Involvement of non-NMDA glutamate receptors in central amygdala in synaptic
      actions of ethanol and ethanol-induced reward behavior.
AB  - The central nucleus of the amygdala (CeA) plays a critical role in positive
      emotional responses that involve stimulus-reward learning and are induced by the
      reinforcing effects of many drugs of abuse, including alcohol. Behavioral studies
      have implicated CeA as a key brain structure in alcohol reward, but the
      underlying mechanisms are still poorly understood. Recent studies have
      demonstrated that both NMDA and non-NMDA receptors in CeA neurons are targets of
      acute and chronic alcohol in naive and alcohol-dependent animals. However, little
      is known about the role of CeA non-NMDA receptors in synaptic actions of alcohol
      and, particularly, in the behavior of alcohol reward. In the present study with
      both whole-cell voltage-clamp recordings in CeA slices in vitro and analysis of
      an animal model of conditioned place preference (CPP) in vivo, we investigated
      the synaptic mechanisms for actions of acute and chronic ethanol on CeA non-NMDA
      receptor functions and their contribution to ethanol-induced reward behavior.
      Acute ethanol significantly inhibited evoked and miniature synaptic currents
      mediated by non-NMDA receptors through inhibitions of both postsynaptic non-NMDA
      receptors and presynaptic glutamate release involving N-type Ca2+ channels. CeA
      neurons from rats exhibiting the ethanol-induced CPP behavior showed a
      significant increase in non-NMDA synaptic transmission. Blockade of this
      increased synaptic transmission through CeA microinjection abolished the CPP
      behavior. These results suggest that acute alcohol inhibits CeA non-NMDA synaptic
      transmission through both presynaptic and postsynaptic mechanisms, and chronic
      alcohol upregulates this synaptic activity, which is required for the alcohol
      induced reward behavior.

PMID- 17215389
TI  - Noncholinergic lesions of the medial septum impair sequential learning of
      different spatial locations.
AB  - The medial septum and diagonal band of Broca (MSDB) are major afferents to the
      hippocampus and are important for learning, memory, and hippocampal theta rhythm.
      In the present study, we assessed the effect of cholinergic or noncholinergic
      MSDB lesions on the sequential learning of different goal locations in the same
      environment, a type of task that is proposed to require hippocampal theta rhythm.
      Rats were administered saline, 192-IgG saporin (SAP), or kainic acid (KA) into
      the MSDB and then behaviorally tested. On any day, a single arm of a radial maze
      was rewarded with food, but the location of this rewarded arm changed between
      days. As in previous studies, intraseptal SAP reduced the number of cholinergic
      neurons although sparing GABAergic septohippocampal neurons. KA had the reverse
      effect, reducing GABAergic septohippocampal neurons and sparing cholinergic
      neurons. KA, but not SAP, impaired performance on the repeated acquisition task.
      Saline and SAP rats showed rapid within-session learning, whereas KA rats were
      much slower to learn the goal location. Performance on a 30 min retention trial
      was also impaired, although this may be attributable to incomplete acquisition.
      These findings provide evidence that noncholinergic, but not cholinergic, MSDB
      neurons are important in helping the animal deal with high loads of memory
      interference, and provides partial support for the idea that hippocampal theta
      rhythm is involved.

PMID- 17215390
TI  - Vascular endothelial growth factor overexpression delays neurodegeneration and
      prolongs survival in amyotrophic lateral sclerosis mice.
AB  - We sought genetic evidence for the involvement of neuronal vascular endothelial
      growth factor (VEGF) in amyotrophic lateral sclerosis (ALS). Mice expressing
      human ALS mutant superoxide dismutase-1 (SOD1) were crossed with mice that
      overexpress VEGF in neurons (VEGF+/+). We report that SOD1(G93A)/VEGF+/+ double
      transgenic mice show delayed motor neuron loss, delayed motor impairment, and
      prolonged survival compared with SOD1(G93A) single transgenics. These findings
      indicate that neuronal VEGF protects against motor neuron degeneration, and may
      have therapeutic implications for ALS.

PMID- 17215391
TI  - Action representation of sound: audiomotor recognition network while listening to
      newly acquired actions.
AB  - The discovery of audiovisual mirror neurons in monkeys gave rise to the
      hypothesis that premotor areas are inherently involved not only when observing
      actions but also when listening to action-related sound. However, the whole-brain
      functional formation underlying such "action-listening" is not fully understood.
      In addition, previous studies in humans have focused mostly on relatively simple
      and overexperienced everyday actions, such as hand clapping or door knocking.
      Here we used functional magnetic resonance imaging to ask whether the human
      action-recognition system responds to sounds found in a more complex sequence of
      newly acquired actions. To address this, we chose a piece of music as a model set
      of acoustically presentable actions and trained non-musicians to play it by ear.
      We then monitored brain activity in subjects while they listened to the newly
      acquired piece. Although subjects listened to the music without performing any
      movements, activation was found bilaterally in the frontoparietal motor-related
      network (including Broca's area, the premotor region, the intraparietal sulcus,
      and the inferior parietal region), consistent with neural circuits that have been
      associated with action observations, and may constitute the human mirror neuron
      system. Presentation of the practiced notes in a different order activated the
      network to a much lesser degree, whereas listening to an equally familiar but
      motorically unknown music did not activate this network. These findings support
      the hypothesis of a "hearing-doing" system that is highly dependent on the
      individual's motor repertoire, gets established rapidly, and consists of Broca's
      area as its hub.

PMID- 17215392
TI  - Neural attunement processes in infants during the acquisition of a language
      specific phonemic contrast.
AB  - To elucidate the developmental neural attunement process in the language-specific
      phonemic repertoire, cerebral hemodynamic responses to a Japanese durational
      vowel contrast were measured in Japanese infants using near-infrared
      spectroscopy. Because only relative durational information distinguishes this
      particular vowel contrast, both first and second language learners have
      difficulties in acquiring this phonemically crucial durational difference.
      Previous cross-linguistic studies conducted on adults showed that phoneme
      specific, left-dominant neural responses were observed only for native Japanese
      listeners. Using the same stimuli, we show that a larger response to the across
      category changes than to the within-category changes occurred transiently in the
      6- to 7-month-old group before stabilizing in the groups older than 12 months.
      However, the left dominance of the phoneme-specific response in the auditory area
      was observed only in the groups of 13 months and above. Thus, the durational
      phonemic contrast is most likely processed first by a generic auditory circuit at
      6-7 months as a result of early auditory experience. The neural processing of the
      contrast is then switched over to a more linguistic circuit after 12 months, this
      time with a left dominance similar to native adult listeners.

PMID- 17215393
TI  - The I-II loop controls plasma membrane expression and gating of Ca(v)3.2 T-type
      Ca2+ channels: a paradigm for childhood absence epilepsy mutations.
AB  - Calcium currents via low-voltage-activated T-type channels mediate burst firing,
      particularly in thalamic neurons. Considerable evidence supports the hypothesis
      that overactive T-channels may contribute to thalamocortical dysrhythmia,
      including absence epilepsy. Single nucleotide polymorphisms in one of the T
      channel genes (CACNA1H, which encodes Ca(v)3.2) are associated with childhood
      absence epilepsy in a Chinese population. Because only a fraction of these
      polymorphisms are predicted to increase channel activity and neuronal firing, we
      hypothesized that other channel properties may be affected. Here we describe that
      all the polymorphisms clustered in the intracellular loop connecting repeats I
      and II (I-II loop) increase the surface expression of extracellularly tagged
      Ca(v)3.2 channels. The functional domains within the I-II loop were then mapped
      by deletion analysis. The first 62 amino acids of the loop (post IS6) are
      involved in regulating the voltage dependence of channel gating and inactivation.
      Similarly, the last 15 amino acids of the loop (pre IIS1) are involved in channel
      inactivation. In contrast, the central region of I-II loop regulates surface
      expression, with no significant effect on channel biophysics. Electrophysiology,
      luminometry, fluorescence-activated cell sorting measurements, and confocal
      microscopy studies demonstrate that deletion of this central region leads to
      enhanced surface expression of channels from intracellular compartments to the
      plasma membrane. These results provide novel insights into how CACNA1H
      polymorphisms may contribute to Ca(v)3.2 channel overactivity and consequently to
      absence epilepsy and establish the I-II loop as an important regulator of
      Ca(v)3.2 channel function and expression.

PMID- 17215394
TI  - Direct astrocytic contacts regulate local maturation of dendritic spines.
AB  - Astrocytes contribute on both development and function of synapses, but it
      remains unclear whether direct astrocytic contacts regulate development of
      individual synapses. Two-photon time-lapse imaging of astrocytic and dendritic
      protrusive activity revealed the correlation of astrocytic contacts with both
      lifetime and morphological maturation of dendritic protrusions. Astrocytic
      motility was essential in maturation of spines, because its suppression by
      manipulating Rac1-dependent signaling in astrocytes resulted in induction of
      longer, filopodia-like dendritic protrusions. Manipulation of ephrin/Eph
      dependent neuron-astrocyte signaling suggested involvement of this signaling
      pathway in astrocyte-dependent stabilization of newly generated dendritic
      protrusions. Our data support a model in which astrocytic protrusive activity in
      development acts as a key local regulator for stabilization of individual
      dendritic protrusions and subsequent maturation into spines.

PMID- 17215395
TI  - Fast synaptic vesicle reuse slows the rate of synaptic depression in the CA1
      region of hippocampus.
AB  - During short-term synaptic depression, neurotransmission rapidly decreases in
      response to repetitive action potential firing. Here, by blocking the vacuolar
      ATPase, alkalinizing the extracellular pH, or exposing hippocampal slices to pH
      buffers, we impaired neurotransmitter refilling, and electrophysiologically
      tested the role of vesicle reuse in synaptic depression. Under all conditions,
      synapses onto hippocampal CA1 pyramidal cells showed faster depression with
      increasing stimulation frequencies. At 20 Hz, compromising neurotransmitter
      refilling increased depression within 300 ms reaching completion within 2 s,
      suggesting a minimal contribution of reserve vesicles to neurotransmission. In
      contrast, at 1 Hz, depression emerged gradually and became significant within 100
      s. Moreover, the depression induced by pH buffers was reversible with a similar
      frequency dependence, suggesting that the frequency-dependent increase in
      depression was caused by impairment of rapid synaptic vesicle reuse. These
      results indicate that synaptic vesicle trafficking impacts the kinetics of short
      term synaptic plasticity at an extremely rapid time scale.

PMID- 17215397
TI  - Motion integration by neurons in macaque MT is local, not global.
AB  - Direction-selective neurons in primary visual cortex have small receptive fields
      that encode the motions of local features. These motions often differ from the
      motion of the object to which they belong and must therefore be integrated
      elsewhere. A candidate site for this integration is visual cortical area MT (V5),
      in which cells with large receptive fields compute the motion of patterns.
      Previous studies of motion integration in MT have used stimuli that fill the
      receptive field, and thus do not test whether motion information is really
      integrated across this whole area. For each MT neuron, we identified two regions
      ("patches") within the receptive field that were approximately equally effective
      in driving responses. We then measured responses to plaids whose component
      gratings overlapped within a patch, and compared them with responses to the same
      component gratings presented in separate patches. Cells that were selective for
      the direction of motion of the whole pattern when the gratings overlapped lost
      this selectivity when the gratings were separated and became selective instead
      for the direction of motion of the individual components. If MT cells simply
      pooled all of the inputs that endow them with a receptive field, they would
      encode all of the motions in the receptive field as belonging to a single object.
      Our results indicate instead that critical elements of the computations
      underlying pattern-direction selectivity in MT are done locally, on a scale
      smaller than the whole receptive field.

PMID- 17215396
TI  - A WAVE-1 and WRP signaling complex regulates spine density, synaptic plasticity,
      and memory.
AB  - The scaffolding protein WAVE-1 (Wiskott-Aldrich syndrome protein family member 1)
      directs signals from the GTPase Rac through the Arp2/3 complex to facilitate
      neuronal actin remodeling. The WAVE-associated GTPase activating protein called
      WRP is implicated in human mental retardation, and WAVE-1 knock-out mice have
      altered behavior. Neuronal time-lapse imaging, behavioral analyses, and
      electrophysiological recordings from genetically modified mice were used to show
      that WAVE-1 signaling complexes control aspects of neuronal morphogenesis and
      synaptic plasticity. Gene targeting experiments in mice demonstrate that WRP
      anchoring to WAVE-1 is a homeostatic mechanism that contributes to neuronal
      development and the fidelity of synaptic connectivity. This implies that
      signaling through WAVE-1 complexes is essential for neural plasticity and
      cognitive behavior.

PMID- 17215398
TI  - Reinforcement learning signals predict future decisions.
AB  - Optimal behavior in a competitive world requires the flexibility to adapt
      decision strategies based on recent outcomes. In the present study, we tested the
      hypothesis that this flexibility emerges through a reinforcement learning
      process, in which reward prediction errors are used dynamically to adjust
      representations of decision options. We recorded event-related brain potentials
      (ERPs) while subjects played a strategic economic game against a computer
      opponent to evaluate how neural responses to outcomes related to subsequent
      decision-making. Analyses of ERP data focused on the feedback-related negativity
      (FRN), an outcome-locked potential thought to reflect a neural prediction error
      signal. Consistent with predictions of a computational reinforcement learning
      model, we found that the magnitude of ERPs after losing to the computer opponent
      predicted whether subjects would change decision behavior on the subsequent
      trial. Furthermore, FRNs to decision outcomes were disproportionately larger over
      the motor cortex contralateral to the response hand that was used to make the
      decision. These findings provide novel evidence that humans engage a
      reinforcement learning process to adjust representations of competing decision
      options.

PMID- 17215399
TI  - Intersectin is a negative regulator of dynamin recruitment to the synaptic
      endocytic zone in the central synapse.
AB  - Intersectin is a multidomain dynamin-binding protein implicated in numerous
      functions in the nervous system, including synapse formation and endocytosis.
      Here, we demonstrate that during neurotransmitter release in the central synapse,
      intersectin, like its binding partner dynamin, is redistributed from the synaptic
      vesicle pool to the periactive zone. Acute perturbation of the intersectin
      dynamin interaction by microinjection of either intersectin antibodies or Src
      homology 3 (SH3) domains inhibited endocytosis at the fission step. Although the
      morphological effects induced by the different reagents were similar, antibody
      injections resulted in a dramatic increase in dynamin immunoreactivity around
      coated pits and at constricted necks, whereas synapses microinjected with the GST
      (glutathione S-transferase)-SH3C domain displayed reduced amounts of dynamin in
      the neck region. Our data suggest that intersectin controls the amount of dynamin
      released from the synaptic vesicle cluster to the periactive zone and that it may
      regulate fission of clathrin-coated intermediates.

PMID- 17215400
TI  - Cholinergic interneurons control the excitatory input to the striatum.
AB  - How the extent and time course of presynaptic inhibition depend on the action
      potentials of the neuron controlling the terminals is unknown. We investigated
      this issue in the striatum using paired recordings from cholinergic interneurons
      and projection neurons. Glutamatergic EPSCs were evoked in projection neurons and
      cholinergic interneurons by stimulation of afferent fibers in the cortex and the
      striatum, respectively. A single spike in a cholinergic interneuron caused
      significant depression of the evoked glutamatergic EPSC in 34% of projection
      neurons located within 100 microm and 41% of cholinergic interneurons located
      within 200 microm. The time course of these effects was similar in the two cases,
      with EPSC inhibition peaking 20-30 ms after the spike and disappearing after 40
      80 ms. Maximal depression of EPSC amplitude was up to 27% in projection neurons
      and to 19% in cholinergic interneurons. These effects were reversibly blocked by
      muscarinic receptor antagonists (atropine or methoctramine), which also
      significantly increased baseline EPSC (evoked without a preceding spike in the
      cholinergic interneuron), suggesting that some tonic cholinergic presynaptic
      inhibition was present. This was confirmed by the fact that lowering
      extracellular potassium, which silenced spontaneously active cholinergic
      interneurons, also increased baseline EPSC amplitude, and these effects were
      occluded by previous application of muscarinic receptor antagonists.
      Collectively, these results show that a single spike in a cholinergic interneuron
      exerts a fast and powerful inhibitory control over the glutamatergic input to
      striatal neurons.

PMID- 17215401
TI  - Activity-dependent control of slow synaptic vesicle endocytosis by cyclin
      dependent kinase 5.
AB  - The stimulated dephosphorylation of the dephosphin group of endocytic proteins by
      calcineurin and their subsequent rephosphorylation by cyclin-dependent kinase 5
      (cdk5) is required for synaptic vesicle (SV) retrieval in central nerve
      terminals. However, the specific endocytic pathway(s) controlled by these enzymes
      is unknown. To address this issue, we combined functional and morphological
      assays of endocytosis in primary neuronal cultures with pharmacological and
      molecular ablation of calcineurin and cdk5 activity. During strong stimulation,
      inhibition of calcineurin or cdk5 blocked uptake of the activity-dependent
      membrane marker FM1-43, but not the more hydrophilic FM2-10. However, FM2-10
      uptake-measured poststimulation was sensitive to cdk5 and calcineurin inhibition,
      indicating that a slow form of endocytosis persists after termination of
      stimulation. In parallel EM studies, inhibition of cdk5 during strong stimulation
      greatly reduced horseradish peroxidase labeling of plasma membrane-derived nerve
      terminal endosomes, but not SVs. Furthermore, during mild stimulation, FM1-43
      uptake was unaffected by cdk5 inhibition and the SV membrane was exclusively
      retrieved via a single SV route, suggesting that recruitment of the endosomal
      route of membrane retrieval is activity dependent. Thus, we propose that the
      calcineurin/cdk5-dependent phosphorylation cycle of the dephosphins specifically
      controls a slow endocytic pathway that proceeds via endosomal intermediates and
      is activated by strong physiological stimulation in central nerve terminals.

PMID- 17215402
TI  - Lack of hypoxia-inducible factor-1 alpha impairs midbrain neural precursor cells
      involving vascular endothelial growth factor signaling.
AB  - Oxygen tension is critical for proliferation of human and murine midbrain-derived
      neural precursor cells (mNPCs). Here, we conditionally inactivated the hypoxia
      responsive transcription factor hypoxia-inducible factor-1alpha (HIF-1alpha) in
      murine NPCs to determine its role in proliferation, survival, and dopaminergic
      differentiation in vitro as well as survival of murine dopaminergic neurons in
      vivo. HIF-1alpha conditional knock-out (HIF-1alpha CKO) mNPCs showed midbrain
      specific impairment of survival and proliferation. Dopaminergic differentiation
      of HIF-1alpha CKO mNPCs in vitro was markedly reduced. Expression of vascular
      endothelial growth factor (VEGF) mRNA was reduced in HIF-1alpha CKO mNPCs,
      whereas erythropoietin signaling was not affected. Treatment of HIF-1alpha CKO
      mNPCs with 50 ng/ml VEGF partially recovered proliferation and dopaminergic
      differentiation in vitro. In substantia nigra (SN) of adult HIF-1alpha CKO mice,
      protein levels of dopaminergic marker molecules such as tyrosine hydroxylase (TH)
      and aldehyde dehydrogenase were reduced by 41 and 61%, respectively. The cell
      survival marker Bcl-2 was reduced by 58% while caspase-3 was activated. Nonbiased
      stereological cell counts of TH-positive neurons in SN of young adult HIF-1alpha
      CKO mice revealed a reduction of 31% compared with cre/wt mice (in which the wild
      type Hif1a allele is expressed in parallel with the Cre recombinase allele).
      However, we found no impairment of striatal dopamine concentrations or locomotor
      behavior. In conclusion, HIF-1alpha seems to be a transcription factor relevant
      to the development and survival of substantia nigra dopaminergic neurons
      involving VEGF signaling.

PMID- 17215403
TI  - Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth
      disease from mitofusin 2 mutations.
AB  - Mutations in the mitochondrial fusion protein mitofusin 2 (MFN2) are the most
      commonly identified cause of Charcot-Marie-Tooth type 2 (CMT2), a dominantly
      inherited disease characterized by degeneration of peripheral sensory and motor
      axons. However, the mechanism by which mutations in this ubiquitously expressed
      mitochondrial fusion protein lead to neuropathy has not yet been elucidated. To
      explore how MFN2 mutations lead to degeneration of peripheral axons, we expressed
      neuropathy-associated forms of MFN2 in cultured dorsal root ganglion neurons,
      cells preferentially affected in CMT2. Disease-associated MFN2 mutant proteins
      induced abnormal clustering of small fragmented mitochondria in both neuronal
      cell bodies and proximal axons. Interestingly, transport of mitochondria in axons
      was significantly impaired in neurons expressing disease-mutated forms of MFN2.
      The diminished axonal mitochondrial transport was not attributable to diminished
      ATP levels in the neurons, and oxidative respiration was normal in mutant MFN2
      expressing cells. Additionally, mitochondrial oxidative enzyme activity was
      normal in muscle mitochondria from a CMT2 patient with an MFN2 mutation, further
      supporting that abnormal mitochondrial transport in neurons is independent from
      an energy production defect. This abnormal mitochondrial trafficking provides a
      likely explanation for the selective susceptibility of the longest peripheral
      axons to MFN2 mutations, in which proper localization of mitochondria is critical
      for axonal and synaptic function.

PMID- 17215404
TI  - Hepatocyte growth factor acts as a motogen and guidance signal for gonadotropin
      hormone-releasing hormone-1 neuronal migration.
AB  - Reproduction in mammals is under the control of the hypothalamic neuropeptide
      gonadotropin hormone-releasing hormone-1 (GnRH-1). GnRH-1-secreting neurons
      originate during embryonic development in the nasal placode and migrate into the
      forebrain along olfactory nerves. Gradients of secreted molecules may play a role
      in this migratory process. In this context, hepatocyte growth factor (HGF) is a
      potential candidate, because it promotes cell motility in developing brain and
      has been shown previously to act as a motogen on immortalized GnRH-1 neurons
      (GN11). In this study, the role of HGF and its receptor Met during development of
      the GnRH-1 system was examined. GnRH-1 cells express Met during their migration
      and downregulate its expression once they complete this process. Tissue-type
      plasminogen activator (tPA), a known HGF activator, is also detected in migratory
      GnRH-1 neurons. Consistent with in vivo expression, HGF is present in nasal
      explants, and GnRH-1 neurons express Met. HGF-neutralizing antibody was applied
      to explants to examine the role of the endogenous growth factor. Migration of
      GnRH-1 cells and olfactory axon outgrowth were significantly reduced, in line
      with disruption of a guidance gradient. Exogenous application of HGF to explants
      increased the distance that GnRH-1 cells migrated, suggesting that HGF also acts
      as a motogen to GnRH-1 neurons. Functional experiments, performed on organotypic
      slice cultures, show that creation of an opposing HGF gradient inhibits GnRH-1
      neuronal migration. Finally, tPA(-/-):uPA(-/-) (urokinase-type plasminogen
      activator(-/-)) knock-out mice exhibit strong reduction of the GnRH-1 cell
      population. Together, these data indicate that HGF signaling via Met receptor
      influences the development of GnRH-1.

PMID- 17215405
TI  - Recovery: an opportunity to transcend our differences.

PMID- 17215406
TI  - Datapoints: The ups and downs of dosing second-generation antipsychotics.

PMID- 17215407
TI  - Innovations: child & adolescent psychiatry: Training in developmental responses
      to trauma for child service providers.
AB  - Youths most at risk of exposure to community violence are often those who are
      least likely to receive the attention of mental health professionals. The column
      describes the development and testing of training about trauma for school
      personnel and other community providers of children's services. The curriculum
      was developed with input from focus groups of school nurses. The one-day training
      sessions address nine areas: normal responses to stress, abnormal responses to
      stress, posttraumatic stress disorder and acute stress disorder, stage theories
      of loss and grief, risk and protective factors, crisis and disaster planning,
      resilience, mental health referral sources, and self-care techniques.

PMID- 17215408
TI  - Law & psychiatry: Telecourt: the use of videoconferencing for involuntary
      commitment hearings in academic health centers.
AB  - The use of videoconferencing for psychiatric involuntary commitment hearings is
      not a recent development. The courts ruled on the constitutionality of these
      proceedings as long ago as 1993. In 2004 University of Michigan Hospital began
      videoconferencing involuntary commitment hearings with Washtenaw County Probate
      Court. The experience of the University of Michigan Health System and the
      Washtenaw Probate Court with telecourt hearings for involuntary commitment has
      proven to benefit the safety and dignity of patients as well as the financial
      health of the medical center.

PMID- 17215410
TI  - A comparison of factors used by physicians and patients in the selection of
      antidepressant agents.
AB  - OBJECTIVES: Involving patients in treatment decisions may reduce premature
      antidepressant treatment terminations and improve clinical and health economic
      outcomes. However, a first step is to determine what information to provide to
      patients to facilitate their decision making. The authors therefore identified,
      valued, and ranked factors of antidepressant treatment selection that are
      relevant to patients and compared them with the opinions of general
      practitioners. METHODS: Matching surveys were developed for patients and
      physicians with feedback from focus groups. In the patient group, participation
      was requested from consecutive patients at four family practice sites in Nova
      Scotia, Canada. Surveys were mailed to 247 randomly selected general
      practitioners. RESULTS: Surveys were completed by 127 patients and 110
      physicians, representing return rates of 70% and 46%, respectively. The most
      valued of the 12 differentiating factors when selecting an antidepressant, ranked
      first by both patients and physicians, was common side effects. Also ranked
      highly by both groups were precautions with antidepressant use, physician
      antidepressant experience, and discontinuation problems. Groups differed in their
      ranking of uncommon serious side effects, time since antidepressants were
      marketed, cost, and dosing schedule. The ranking distributions were significantly
      different for six of 12 factors between patients and general practitioners
      (Wilcoxon ranked-sum test). Patient experience with antidepressants did not
      influence factor value. CONCLUSIONS: The data demonstrate moderate disagreement
      between patients and general practitioners regarding the relative value of
      antidepressant selection factors. The effect of this disagreement on treatment
      adherence and other outcomes requires further investigation, as improving patient
      physician concordance regarding antidepressant choices may lead to improved
      treatment acceptance.

PMID- 17215409
TI  - Changes in the quality of care for bipolar I disorder during the 1990s.
AB  - OBJECTIVE: This study estimated changes during the 1990s in the quality of usual
      care treatment among persons diagnosed as having bipolar I disorder in a
      privately insured population. METHODS: Retrospective private insurance
      administrative data were analyzed for enrollees aged 18 to 64 who were diagnosed
      as having bipolar I disorder during 1991 (431 person-years), 1994 (598 person
      years), and 1999 (600 person-years). Medication and psychotherapy quality
      indicators were derived from bipolar disorder expert guidelines published in
      1994, which were consistent with guidelines published until year 2002. RESULTS:
      The unadjusted prevalence of receiving any lithium, valproate, or carbamazepine
      improved over the study period (68 percent in 1991, 64 percent in 1994, and 77
      percent in 1999), whereas, compared with 1991, receiving any antidepressant in
      the absence of lithium, valproate, or carbamazepine increased in 1994 and then
      declined in 1999 (13 percent in 1991, 23 percent in 1994, and 14 percent in
      1999). The unadjusted prevalence of receiving any psychotherapy declined steadily
      and sharply (94 percent in 1991, 89 percent in 1994, and 69 percent in 1999). The
      unadjusted prevalence of receiving any lithium, valproate, or carbamazepine and
      therapy together declined over time (65 percent in 1991, 58 percent in 1994, and
      54 percent in 1999). After the analyses adjusted for patient characteristics,
      these changes were significant from p<.01 to p<.001. CONCLUSIONS: The prevalence
      of receiving the pharmacotherapy recommended in the guidelines improved after
      guideline publication in 1994, whereas other quality measures that included
      receiving psychotherapy declined throughout the study period. These results
      suggest different psychotherapeutic modalities are under differing constraints
      under managed care, constraints that overpower consensus in the literature of
      quality practice. Policy makers should measure a variety of key therapeutic
      modalities when measuring quality in order to capture these differences.

PMID- 17215411
TI  - Factors associated with stigma among caregivers of patients with bipolar disorder
      in the STEP-BD study.
AB  - OBJECTIVE: Little is known about the factors contributing to mental illness
      stigma among caregivers of people with bipolar disorder. METHODS: A total of 500
      caregivers of patients participating in the Systematic Treatment Enhancement
      Program for Bipolar Disorder (STEP-BD) study were interviewed in a cross
      sectional design on measures of stigma, mood, burden, and coping. Relatives and
      friends with bipolar disorder were assessed on measures of diagnosis and clinical
      status, determined by a days-well measure derived from psychiatrist ratings of
      DSM-IV episode status. Because patients' clinical status varied widely, separate
      models were run for patients who were euthymic for at least three-fourths of the
      past year (well group) and for those who met criteria for an affective episode
      for at least one-fourth of the previous year (unwell group). Stepwise multiple
      regression was used to identify patient, illness, and caregiver characteristics
      associated with caregiver stigma. RESULTS: In the unwell group, greater mental
      illness stigma was associated with bipolar I (versus II) disorder, less social
      support for the caregiver, fewer caregiver social interactions, and being a
      caregiver of Hispanic descent. In the well group, greater stigma was associated
      with being a caregiver who is the adult child of a parent with bipolar disorder,
      who has a college education, who has fewer social interactions, and who cares for
      a female bipolar patient. CONCLUSIONS: Mental illness stigma was found to be
      prevalent among caregivers of persons with bipolar disorder who have active
      symptoms as well as for caregivers of those who have remitted symptoms. Stigma is
      typically associated with factors identifying patients as "different" during
      symptomatic periods. Research is needed to understand how the stigma experienced
      by caregivers during stable phases of illness differs from the stigma experienced
      during patients' illness states.

PMID- 17215412
TI  - Changes in health care use and costs after a break in Medicaid coverage among
      persons with depression.
AB  - OBJECTIVE: The objective of this study was to assess changes in individual
      beneficiaries' utilization and expenditures that occur when individuals with
      depression, who often require maintenance treatment, return to Medicaid after a
      period of interrupted Medicaid coverage. METHODS: Data from 1999 to 2002 Florida
      Medicaid claims from and eligibility files for beneficiaries with depression
      whose coverage was interrupted (N=1,946) were used to assess individual changes
      in the number of inpatient episodes, length of inpatient stay, emergency
      department visits, and total Medicaid expenditures between the three-month period
      immediately before and the three-month period immediately after an interruption
      in coverage. Multivariate analyses were used to assess how beneficiary
      characteristics are associated with changes in utilization and expenditures.
      RESULTS: The number of inpatient episodes increased by .054 episode (p<.001), the
      length of inpatient stay increased by .32 day (p<.001), the number of emergency
      department visits increased by .57 visit (p<.001), and total Medicaid
      expenditures increased by 430 dollars (p<.001) in the three-month period after an
      interruption in coverage of more than one month. Individuals with depression who
      qualified for Medicaid because of a disability had a greater likelihood of
      experiencing higher expenditures after an interruption than individuals who were
      not disabled. CONCLUSIONS: Utilization of emergency and inpatient services and
      Medicaid expenditures significantly increased for beneficiaries with depression
      when they returned to Medicaid after experiencing a temporary loss in coverage,
      especially for beneficiaries with a documented disability. These findings point
      to the need for further research to assess the impact of interruptions in
      Medicaid.

PMID- 17215413
TI  - Racial and ethnic disparities in SSRI availability in substance abuse treatment.
AB  - OBJECTIVE: The high rate of co-occurrence of psychiatric and substance use
      disorders suggests that specialty substance abuse treatment facilities may be an
      important site for the delivery of psychotropic medications. However, the
      literature suggests there may be associations between the percentage of racial
      and ethnic minority clients and the availability of selective serotonin reuptake
      inhibitors (SSRIs) in these facilities. METHODS: Survey data from the National
      Treatment Center Study, comprising nationally representative samples of 326
      publicly funded and 339 privately funded substance abuse treatment centers, were
      used to measure the availability of SSRI medications from 2002 to 2004.
      Independent variables included the percentages of African-American and Hispanic
      clients, center type, organizational affiliation, region, size, accreditation
      status, presence of an integrated care program, and physician availability.
      RESULTS: SSRIs were available in 48% of the centers. Logistic regression analysis
      indicated that greater minority representation in centers' caseloads was
      negatively associated with the availability of SSRIs. The association between the
      percentage of African-American clients and SSRI availability was fully mediated
      by the addition of factors related to treatment inputs, such as the presence of a
      physician on staff or contract and the presence of an integrated care program.
      With organizational and treatment characteristics factored out, there was a
      negative association between the percentage of Hispanic clients and the
      availability of SSRIs. CONCLUSIONS: Although SSRIs were available in nearly half
      of these substance abuse treatment settings, racial and ethnic disparities exist
      in the availability of these medications.

PMID- 17215414
TI  - Do Canada and the United States differ in prevalence of depression and
      utilization of services?
AB  - OBJECTIVE: This study compared the prevalence of depression and the determinants
      of mental health service use in Canada and the United States. METHODS: The study
      used data from preliminary analyses of the 2003 Joint Canada/United States Survey
      of Health, which measured Canadian (N=3,505) and United States (N=5,183) resident
      ratings of health and health care services. Cross-national comparisons were made
      for the 12-month prevalence of DSM-IV major depression, 12-month service use for
      mental health reasons according to the type of professional seen, and
      determinants of service use. RESULTS: The rates of depression were similar in
      Canada (8.2%) and the United States (8.7%). However, U.S. respondents without
      medical insurance were twice as likely as Canadian respondents and U.S.
      respondents with medical insurance to meet the criteria for depression. Rates of
      mental health service use did not differ between Canada (10.1%) and the United
      States (10.6%). In the United States, medical insurance was not a determinant
      factor of service use. However, U.S. respondents with no medical insurance were
      more likely than the other two groups to report an unmet need. Also, among those
      with depression, U.S. respondents with no medical insurance were less likely to
      use any type of mental health service (36.5%) than U.S. respondents with medical
      insurance (55.7%) and Canadians (55.7%). Further, a positive correlation between
      a mental health need and service use was observed in Canada but not for those
      without medical insurance in the United States. CONCLUSIONS: There was no
      difference in the prevalence of depression and mental health service use between
      Canada and the United States. Among those with depression, however, disparities
      in treatment seeking were found to be associated with medical insurance in the
      United States. Both Canada and the United States need to improve access to health
      services for those with mental disorders, and special attention is needed for
      those without medical insurance in the United States.

PMID- 17215415
TI  - Factors associated with primary care clinicians' choice of a watchful waiting
      approach to managing depression.
AB  - OBJECTIVES: Watchful waiting to manage depression in primary care may be an
      appropriate management approach for some patients who present with less severe
      depression. This study examined factors associated with primary care clinicians'
      choice of a watchful waiting approach to care management for depression. METHODS:
      Secondary data were analyzed from Partners in Care, which examined dissemination
      of best practices for depression in primary care. Primary care clinicians'
      decisions regarding watchful waiting were examined by using the baseline survey
      data from Partners in Care completed by clinicians and patients from February
      1996 to March 1997. Participants were 167 primary care clinicians from 46
      practices of seven managed care organizations across the United States and their
      1,187 patients with depression. Primary care clinicians' proclivity for watchful
      waiting was examined by using a brief scenario describing a patient with major
      depressive disorder. RESULTS: Thirty-four clinicians (20 percent) reported a
      strong proclivity to use watchful waiting for the patient in the scenario. The
      proclivity was significantly associated with clinicians' reports of the
      proportion of their actual patients with whom they used this approach. Clinicians
      were significantly more likely to choose watchful waiting for their actual
      patients if they had more psychotherapy knowledge (p=.035) or perceived that the
      need to treat the patient's medical illness was more important than the need to
      treat his or her mental illness (p=.046) and were less likely to choose a
      watchful waiting approach if they perceived the lack of availability of mental
      health professionals as a barrier (p=.050). CONCLUSIONS: Primary care clinicians'
      knowledge of treatment and perception of barriers influence their proclivity for
      watchful waiting. Clinician education to promote appropriate use of watchful
      waiting on the basis of clinical need is recommended.

PMID- 17215416
TI  - Antidepressant utilization in British Columbia from 1996 to 2004: increasing
      prevalence but not incidence.
AB  - OBJECTIVES: Expenditures on antidepressants in Canada are rapidly increasing; yet
      few studies have analyzed the characteristics of antidepressant users. This study
      investigated the prevalence and incidence of antidepressant use in British
      Columbia over eight years. METHODS: Antidepressant utilization and demographic
      data were assessed for the population of British Columbia from 1996 to 2004.
      Prescription claims were identified within the PharmaNet database for serotonin
      reuptake inhibitors (SSRI), tricyclics, monoamine oxidase inhibitors, bupropion
      (categorized separately for smoking cessation), and "novel" antidepressants, such
      as venlafaxine. Incident utilization (dispensed "first" antidepressant after two
      years without an antidepressant claim) and prevalent utilization were analyzed.
      All cohort members were required to have continuous registration with British
      Columbia medical services for at least two years before the first antidepressant
      claim. RESULTS: Prevalence of antidepressant use doubled, from 34 to 72 users per
      1,000 population, between 1996 and 2004. The prevalence of particular classes of
      antidepressants also changed over time. Prevalence of novel antidepressants and
      SSRIs increased, although incidence of SSRIs decreased. Prevalent and incident
      use of bupropion for smoking cessation peaked in 1999 but then declined.
      Quarterly incident antidepressant use increased in 1998 and 1999 (6.5 and 11.3
      users per 1,000) but decreased through 2004 (4.2 users per 1,000). Those aged 20
      to 44 years and those aged 45 to 64 years showed the greatest peak in incident
      antidepressant use. A socioeconomic gradient in prescribing was observed.
      CONCLUSIONS: Prevalent antidepressant use has increased dramatically since 1996.
      By contrast, incident use increased from 1998 to 1999 but then decreased through
      2004. Many complex factors likely contribute to antidepressant prescribing
      patterns.

PMID- 17215417
TI  - Patterns of psychotropic drug prescription for U.S. patients with diagnoses of
      bipolar disorders.
AB  - OBJECTIVE: Bipolar disorders are prevalent major illnesses with high rates of
      morbidity, comorbidity, disability, and mortality. A growing number of
      psychotropic drugs are used to treat bipolar disorder, often off-label and in
      untested, complex combinations. METHODS: To quantify utilization rates for
      psychotropic drug classes, this study used the 2002-2003 U.S. national MarketScan
      research databases to identify 7,760 persons with ICD-9 bipolar disorder
      subtypes. Survival analysis was used to estimate times until initial
      monotherapies were augmented, changed, or discontinued. RESULTS: The most
      commonly prescribed first drug class was antidepressants (50% of patients),
      followed by mood stabilizers (25%: anticonvulsants, 17%, and lithium, 8%),
      sedatives (15%), and antipsychotics (11%). At study midpoint only 44% of patients
      were receiving monotherapy. Those receiving monotherapy were ranked by initial
      drug prescribed and percentage of patients (bipolar I and bipolar II):
      antidepressants (55% and 65%), lithium (51% and 41%), antipsychotics (32% and
      31%), anticonvulsants (28% and 29%), and sedatives (28%, 25%). Median time to
      adding another psychotropic was 2.5-times less than median time to changing the
      initial treatment (16.4 compared with 40.9 weeks), and stopping was rare. Median
      weeks until therapy was changed in any way for 25% of patients was as follows:
      lithium, 29 weeks; antidepressants, 13; anticonvulsants, 13; antipsychotics, 13;
      and sedatives, 9. CONCLUSIONS: Antidepressants were the first-choice agent twice
      as often as mood stabilizers. Lithium was sustained longer than monotherapy with
      other mood stabilizers. Time to augmentation was much shorter than time to change
      or discontinuation.

PMID- 17215418
TI  - Diagnostic and other correlates of HIV risk behaviors in a probability sample of
      homeless adults.
AB  - OBJECTIVES: This study assessed the relationship between psychiatric disorders,
      including substance abuse and dependence, and risk behaviors for contracting HIV.
      METHODS: A probability sample of 218 homeless men and women were recruited from
      food programs and shelters assisting homeless individuals in an urban
      metropolitan community. Mood disorders, schizophrenia, and substance abuse and
      dependence diagnoses were assessed with the Diagnostic Interview Schedule
      (version 3A). Level of sexual activity and HIV risk behaviors (such as history of
      sexually transmitted diseases, ratio of protected sex, trading sex for money or
      drugs, sex with a prostitute, and sex under the influence of alcohol or drugs)
      also were measured. RESULTS: Substance abuse and dependence and the length of the
      homelessness episode at baseline were associated with the highest risk of
      engaging in HIV risk behaviors. However, there was no relationship between mood
      disorders, schizophrenia, and HIV risk behaviors. CONCLUSIONS: This study
      provides evidence that individuals who are homeless for extended periods and have
      a diagnosis of substance abuse or dependence may be especially vulnerable to
      engaging in risky sexual behaviors and contracting HIV. The findings highlight
      the importance of tailoring treatment programs to the specific needs of homeless
      individuals.

PMID- 17215419
TI  - Cost shifting under managed behavioral health care.
AB  - OBJECTIVE: The study examined whether a managed behavioral health care
      organization (MBHO) shifted treatment costs. METHODS: Four years of claims data
      (1991-1995) from an insurer that introduced an MBHO in 1992 to control treatment
      costs were analyzed. Although the MBHO was not at direct financial risk for
      specialty mental health treatment, it faced incentives related to reputation and
      contract renewal to shift costs to primary care treatment or prescription drugs.
      It was hypothesized that if cost shifting occurred, an increase would be noted in
      the use of psychotropic medications without concurrent use of specialty mental
      health treatment. Simple t tests and a generalized estimating equations probit
      specification were used to test this hypothesis. Separate tests were performed
      for use of any psychotropic medication, any newer antidepressant, and any
      stimulant in a large employer group that simultaneously implemented parity
      coverage (75,360 enrollees) and a group of smaller employers that did not (9,228
      enrollees). RESULTS: The use of any psychotropic medication rose 64% in relative
      terms (p<.001) over the four-year period among enrollees of the large employer
      group and by 87% in the smaller groups (p<.001). In general, there were downward
      secular trends in the use of psychotropic medications without specialty care.
      Introduction of the MBHO was not significantly associated with the use of
      psychotropic medication alone. For newer antidepressants, introduction of the
      MBHO was associated in the large group with a 2.4 (p=.003) absolute percentage
      point decrease in medication use alone. CONCLUSIONS: No evidence was found to
      suggest that the MBHO shifted treatment costs.

PMID- 17215420
TI  - Psychiatric residences: notification, NIMBY, and neighborhood relations.
AB  - OBJECTIVE: Federal legislation has given mental health agencies the authority to
      forego notifying neighbors when establishing shared, supervised houses and
      apartments for individuals with severe mental illness, but many continue to
      notify neighbors in the belief that outreach enhances community integration. This
      study examined the associations between notification strategies and initial
      neighborhood opposition and longer-term neighborhood relations. METHODS:
      Telephone interviews were conducted with 169 mental health administrators in
      seven states who described the notification strategy and short- and long-term
      neighborhood responses to their most recently established shared, supervised
      residence. Additional data on neighborhood relations were collected in interviews
      with 138 staff who worked on site at the residences described by the mental
      health administrators. RESULTS: Just under half of the agencies used a strategy
      that involved notification of neighbors, and those organizations were
      significantly more likely to experience initial opposition (59% of notifiers
      experienced opposition compared with 35% of non-notifiers). Those who notified
      neighbors were more likely to initiate activities such as an open house with
      neighbors after the site was established. There were no significant associations
      between current neighborhood attitudes and initial notification strategies or
      initial opposition. Agencies that initiated postsiting social activities with
      neighbors were significantly more likely to report "very accepting" attitudes.
      CONCLUSIONS: Administrators who use notification may experience higher levels of
      initial opposition, but longer-term neighborhood relations may not vary
      significantly regardless of whether neighbors were notified or whether initial
      opposition was present. Some agency-sponsored postsiting activities may
      facilitate substantive connections with neighbors.

PMID- 17215421
TI  - Criminal records of persons served in the public mental health system.
AB  - OBJECTIVE: The authors examined the frequency and severity of arrests of persons
      served by Medicaid as well as public mental health treatment patterns before and
      after arrest. METHODS: A random sample of 6,624 persons was drawn from claims of
      the public mental health system in Los Angeles County between July 1993 and June
      2001. Clients' claims were matched to criminal justice records from 1991 to 2001.
      Cross-tabulations and logistic regression analyses were used to examine the
      likelihood and seriousness of criminal involvement, as well as clients'
      involvement in mental health treatment around the time of the arrest. RESULTS:
      Twenty-four percent of the sample had at least one arrest over the ten-year
      period. Sixty-two percent of arrested individuals had as their most serious
      offense a nonviolent crime. Half of all observed arrests did not lead to
      conviction. There was no statistical difference in the total treatment services
      received between arrested and not-arrested individuals. Among those arrested,
      there was only a small difference in the likelihood of receiving treatment
      services before and after arrest. CONCLUSIONS: Almost a quarter of persons with
      serious mental illness were arrested at least once over ten years. More than one
      third of these individuals were arrested for violent crimes, with drug crimes the
      second most common category. The seriousness of the offense varied with
      diagnosis. Arrest was not associated with meaningful increases in service use,
      pointing to potential missed opportunities for treatment.

PMID- 17215422
TI  - A comparison of assertive community treatment and intensive case management for
      patients in rural areas.
AB  - OBJECTIVE: This article reviews the evidence for the effectiveness of community
      based services for rural areas, specifically assertive community treatment and
      intensive case management. Service delivery to persons with severe mental illness
      in rural areas is challenged by low population densities, limited services, and
      shortages of professionals. METHODS: A comprehensive literature search identified
      six studies of rural assertive community treatment, only two of which were
      controlled studies, and four rural intensive case management studies, only one of
      which was a controlled study. Assertive community treatment would seem ideally
      suited to areas lacking services because of its self-contained multidisciplinary
      treatment team approach. However, rural programs have been forced to make several
      adaptations to the assertive community treatment model, including smaller teams,
      less comprehensive staff, and less intensive services. There is no published
      evidence that these adaptations are able to produce the same results as full
      fidelity teams. Some believe that intensive case management may be an alternative
      to assertive community treatment in rural settings because intensive case
      management emphasizes individual caseloads, fewer staff, less intensive contacts,
      and brokered services. CONCLUSIONS: The evidence suggests that intensive case
      management programs are effective only in community settings where there is an
      ample supply of treatment and support services. To build the evidence base for
      the effectiveness of these models, much more attention needs to be focused on
      evaluating the current wave of assertive community treatment and intensive case
      management dissemination in rural areas.

PMID- 17215423
TI  - Generic fluoxetine and choice of antidepressant medication.
AB  - OBJECTIVE: In 2002 generic fluoxetine, the first generic product in a relatively
      expensive medication class, became available at Veterans Affairs medical centers
      at only 5% of its previous cost. This study examined whether its availability was
      associated with an increase in use compared with other medications. METHODS: All
      new starts of 15 antidepressants during fiscal year (FY) 2001 (before generic
      fluoxetine became available) and FY2003 were identified from administrative
      records, and the change in proportions of new starts across years was examined.
      RESULTS: Altogether, 55,673 patients had a new start on antidepressants in FY2001
      and 48,002 had a new start in FY2003. The percentage of fluoxetine prescriptions
      (both branded and generic) rose only 1.2%--from 8.3% in FY2001 to 9.5% in FY2003.
      CONCLUSIONS: Only a small increase was found in the rate of new starts of
      fluoxetine in the year after its release as a low-cost generic. There appear to
      be untapped opportunities to realize savings for antidepressants with appropriate
      administrative mechanisms and incentives.

PMID- 17215424
TI  - Caregiver depression and medication use by youths with ADHD who receive services
      in the public sector.
AB  - OBJECTIVE: This study examined caregiver depression and medication use by youths
      with attention-deficit hyperactivity disorder (ADHD) in the public sector.
      METHODS: Multivariate logistic regression models were created for 390 youths six
      to 17 years of age who met ADHD criteria on the Diagnostic Interview Schedule for
      Children (DISC) and were enrolled in a prospective study of youths served in
      public-sector service systems. The dependent variable was caregiver report of
      youth medication use for ADHD in the 12 months before the 24-month interview.
      RESULTS: Only 38% of youths with DISC diagnoses of ADHD were using medication.
      Youths whose caregivers had depression (41% of the sample) were half as likely as
      other youths to use medication. Younger age, public insurance, caregiver report
      of diagnosis, and receipt of medical, mental health, or school services also
      predicted use. CONCLUSIONS: Caregiver depression and its association with
      medication use warrant further exploration.

PMID- 17215425
TI  - Restrictions on antidepressant medications for children: a review of Medicaid
      policy.
AB  - OBJECTIVE: This study evaluated Medicaid's prior-authorization policies
      restricting the prescribing of antidepressant medications for children. METHODS:
      Medicaid program prior-authorization policies for antidepressant medications were
      obtained for all available states. All criteria needed for authorization were
      recorded, with a focus on policies that applied specifically to children.
      RESULTS: Data from 49 states and the District of Columbia revealed that 30 states
      (60%) required prior authorization for antidepressants, of which eight (27%) made
      specific provisions for children. These provisions varied across states. In most
      states fluoxetine could be prescribed for children with minimal restrictions, and
      two states had prior-authorization policies that strongly encouraged pediatric
      patients to use fluoxetine. State policies regarding other selective serotonin
      reuptake inhibitors varied widely. CONCLUSIONS: Although relatively few states
      included provisions for children in prior-authorization requirements for
      antidepressants, in states that did, the policies implemented varied widely.
      These findings raise important questions about the rational development of
      prescription drug reimbursement policy.

PMID- 17215426
TI  - Shared decision making.

PMID- 17215427
TI  - Shared decision making.

PMID- 17215429
TI  - Kinship status in CATIE.

PMID- 17215431
TI  - Conditional release and reduced mortality.

PMID- 17215433
TI  - Proteomic analysis of the airway surface liquid: modulation by proinflammatory
      cytokines.
AB  - The airway surface is covered by a fluid, the airway surface liquid, interposed
      between the mucous layer and the epithelium. The airway surface liquid contains
      proteins, secreted by different cell types, that may have pro-/anti-inflammatory
      or bactericidal functions or have a role in the mucociliary clearance. We have
      used a proteomics approach to identify the proteins secreted by an isolated in
      vitro model of human airway epithelium, at resting and under proinflammatory
      conditions, as a strategy to define the factors involved in epithelial barrier
      function. To this aim, we have analyzed the airway surface liquid from human
      bronchial epithelial cells grown as polarized monolayers in the presence and
      absence of inflammatory stimuli such as IL-4, IL-1beta, TNF-alpha, and IFN-gamma.
      Two-dimensional electrophoresis followed by mass spectrometry analysis has
      allowed the identification of approximately 175 secreted protein spots, among
      which are immune-related proteins, structural proteins, an actin severer, some
      protease inhibitors, and a metalloproteinase. Comparisons between treated and
      untreated conditions have shown that the expression of several proteins was
      significantly modified by the different cytokines. Our results indicate that the
      surface epithelium is an active player in the epithelial barrier function and
      that inflammatory conditions may modulate protein secretion.

PMID- 17215434
TI  - In utero nicotine exposure alters fetal rat lung alveolar type II cell
      proliferation, differentiation, and metabolism.
AB  - We recently suggested that alveolar interstitial fibroblast-to-myofibroblast
      transdifferentiation may be a key mechanism underlying in utero nicotine-induced
      lung injury. However, the effects of in utero nicotine exposure on fetal alveolar
      type II (ATII) cells have not been fully determined. Placebo, nicotine (1 mg/kg),
      or nicotine (1 mg/kg) + the peroxisome proliferator-activated receptor (PPAR)
      gamma agonist prostaglandin J(2) (PGJ(2), 0.3 mg/kg) was administered
      intraperitoneally once daily to time-mated pregnant Sprague-Dawley rats from
      embryonic day 6 until their death on embryonic day 20. Fetal ATII cells were
      isolated, and ATII cell proliferation, differentiation (surfactant synthesis),
      and metabolism (metabolic profiling with the stable isotope [1,2-(13)C(2)]-d
      glucose) were determined after nicotine exposure in utero or in vitro. In utero
      nicotine exposure significantly stimulated ATII cell proliferation,
      differentiation, and metabolism. Although the effects on ATII cell proliferation
      and metabolism were almost completely prevented by concomitant treatment with
      PGJ(2), the effects on surfactant synthesis were not. On the basis of in utero
      and in vitro data, we conclude that surfactant synthesis is stimulated by
      nicotine's direct effect on ATII cells, whereas cell proliferation and metabolism
      are affected via a paracrine mechanism(s) secondary to its effects on the
      adepithelial fibroblasts. These data provide evidence for direct and indirect
      effects of in utero nicotine exposure on fetal ATII cells that could permanently
      alter the "developmental program" of the developing lung. More importantly,
      concomitant administration of PPAR-gamma agonists can effectively attenuate many
      of the effects of in utero exposure to nicotine on ATII cells.

PMID- 17215435
TI  - Hyperoxic conditions inhibit airway smooth muscle myosin phosphatase in rat pups.
AB  - Exposure of rat pups to 100% oxygen is a model for studying neonatal lung injury.
      Airway reactivity is increased in this model, in part due to impaired airway
      smooth muscle (ASM) relaxation. We compared biochemical determinants of ASM
      contractility in rat pups exposed to 100% oxygen for 7 days vs. littermates
      raised in room air. The baseline quantities of ASM contractile proteins, extent
      of phosphorylation of the 20-kDa myosin regulatory light chain (LC(20)), and
      amount of the myosin-binding subunit of smooth muscle myosin phosphatase (MYPT)
      were all comparable between the two groups. Bethanechol-induced contraction
      increased the extent of phosphorylation of both LC(20) and MYPT in the hyperoxic
      group (45% and 70% over control, respectively). Relaxation after electrical field
      stimulation demonstrated greater phosphorylation of both LC(20) and MYPT in the
      hyperoxic group compared with controls (67% and 84%, respectively). To determine
      if hyperoxia induced changes in the isoforms of MYPT, isoform expression was also
      compared but differences were not found. To determine potential mechanisms
      whereby MYPT phosphorylation was increased by hyperoxia, separate tracheas were
      treated with the Rho kinase inhibitor Y-27632. This treatment completely
      eliminated differences in MYPT phosphorylation between the groups. Because
      phosphorylation of MYPT impairs the phosphatase activity of myosin phosphatase,
      these data suggest that hyperoxic conditioning during early postnatal life
      impairs relaxation through prolonging LC(20) phosphorylation. This mechanism
      might contribute to increased ASM reactivity seen in bronchopulmonary dysplasia.

PMID- 17215436
TI  - A single transient episode of hyperammonemia induces long-lasting alterations in
      protein kinase A.
AB  - Hepatic encephalopathy in patients with liver disease is associated with poor
      prognosis. This could be due to the induction by the transient episode of hepatic
      encephalopathy of long-lasting alterations making patients more susceptible. We
      show that a single transient episode of hyperammonemia induces long-lasting
      alterations in signal transduction. The content of the regulatory subunit of the
      protein kinase dependent on cAMP (PKA-RI) is increased in erythrocytes from
      cirrhotic patients. This increase is reproduced in rats with portacaval
      anastomosis and in rats with hyperammonemia without liver failure, suggesting
      that hyperammonemia is responsible for increased PKA-RI in patients. We analyzed
      whether there is a correlation between ammonia levels and PKA-RI content in
      patients. All cirrhotic patients had increased content of PKA-RI. Some of them
      showed normal ammonia levels but had suffered previous hyperammonemia episodes.
      This suggested that a single transient episode of hyperammonemia could induce the
      long-lasting increase in PKA-RI. To assess this, we injected normal rats with
      ammonia and blood was taken at different times. Ammonia returned to basal levels
      at 2 h. However, PKA-RI was significantly increased in blood cells from rats
      injected with ammonia 3 wk after injection. In conclusion, it is shown that a
      single transient episode of hyperammonemia induces long-lasting alterations in
      signal transduction both in blood and brain. These alterations may contribute to
      the poor prognosis of patients suffering hepatic encephalopathy.

PMID- 17215437
TI  - IL-4 gene transfer to the small bowel serosa leads to intestinal inflammation and
      smooth muscle hyperresponsiveness.
AB  - Intestinal mucosal inflammation can lead to altered function of the underlying
      smooth muscle, which becomes hyperreactive to most contractile stimuli. Through
      nematode parasite infection models, T helper type 2 (Th2) cytokines have been
      implicated in intestinal muscle dysfunction; however, the mechanisms involved and
      the relevance of these findings to other forms of intestinal inflammation are
      unclear. Through gene transfer, we explored whether the Th2 cytokine IL-4 can
      mediate changes in longitudinal muscle function in the context of an adenoviral
      infection. Following abdominal surgery on mice, control beta-galactosidase
      encoding recombinant adenoviruses and IL-4-encoding adenoviruses were applied to
      the serosal surface of the jejunum, leading to infection of cells in the serosa
      and in the mesentery. Marker transgene expression lasted for 3 wk and was
      accompanied by the recruitment of macrophages, lymphocytes, and neutrophils into
      the peritoneal cavity and mild inflammation at the site of infection. IL-4
      transgene expression led to a stronger inflammatory response characterized by
      tissue eosinophilia and increased numbers of peritoneal mast cells and plasma
      cells. Whereas control virus infection had no effect on intestinal muscle
      function, infection with the IL-4 virus led to significant jejunal muscle
      hypercontractility, evident by day 7 postinfection. This modulation of smooth
      muscle function was shown to be IL-4 specific, since the application of an IL-5
      encoding adenovirus induced tissue eosinophilia but did not alter muscle
      function. These results highlight an important causal role for IL-4 in the
      pathological regulation of enteric smooth muscle function and identify a novel
      strategy for gene transfer to the intestine.

PMID- 17215438
TI  - Intestinal epithelial cell-derived interleukin-7: A mechanism for the alteration
      of intraepithelial lymphocytes in a mouse model of total parenteral nutrition.
AB  - Total parenteral nutrition (TPN), with the absence of enteral nutrition, results
      in profound changes to both intestinal epithelial cells (EC) as well as the
      adjacent intraepithelial lymphocyte (IEL) population. Intestinal EC are a rich
      source of IL-7, a critical factor to support the maintenance of several lymphoid
      tissues, and TPN results in marked EC changes. On this basis, we hypothesized
      that TPN would diminish EC-derived IL-7 expression and that this would contribute
      to the observed changes in the IEL population. Mice received enteral food and
      intravenous crystalloid solution (control group) or TPN. TPN administration
      significantly decreased EC-derived IL-7 expression, along with significant
      changes in IEL phenotype; decreased IEL proliferation; and resulted in a marked
      decrease in IEL numbers. To better determine the relevance of TPN-related changes
      in IL-7, TPN mice supplemented with exogenous IL-7 or mice allowed ad libitum
      feeding and treated with exogenous administration of anti-IL-7 receptor (IL-7R)
      antibody were also studied. Exogenous IL-7 administration in TPN mice
      significantly attenuated TPN-associated IEL changes, whereas blocking IL-7R in
      normal mice resulted in several similar changes in IEL to those observed with
      TPN. These findings suggest that a decrease in EC-derived IL-7 expression may be
      a contributing mechanism to account for the observed TPN-associated IEL changes.

PMID- 17215439
TI  - Renal function in mice with targeted disruption of the A isoform of the Na-K-2Cl
      co-transporter.
AB  - Three different full-length splice isoforms of the Na-K-2Cl co-transporter
      (NKCC2/BSC1) are expressed along the thick ascending limb of Henle (TAL),
      designated NKCC2A, NKCC2B, and NKCC2F. NKCC2F is expressed in the medullary,
      NKCC2B mainly in the cortical, and NKCC2A in medullary and cortical portions of
      the TAL. NKCC2B and NKCC2A were shown to be coexpressed in the macula densa (MD)
      segment of the mouse TAL. The functional consequences of the existence of three
      different isoforms of NKCC2 are unclear. For studying the specific role of NKCC2A
      in kidney function, NKCC2A-/- mice were generated by homologous recombination.
      NKCC2A-/- mice were viable and showed no gross abnormalities. Ambient urine
      osmolarity was reduced significantly in NKCC2A-/- compared with wild-type mice,
      but water deprivation elevated urine osmolarity to similar levels in both
      genotypes. Baseline plasma renin concentration and the effects of a high- and a
      low-salt diet on plasma renin concentration were similar in NKCC2A+/+ and -/-
      mice. However, suppression of renin secretion by acute intravenous saline loading
      (5% of body weight), a measure of MD-dependent inhibition of renin secretion, was
      reduced markedly in NKCC2A-/- mice compared with wild-type mice. Cl and water
      absorption along microperfused loops of Henle of NKCC2A-/- mice were unchanged at
      normal flow rates but significantly reduced at supranormal flow. Tubuloglomerular
      feedback function curve as determined by stop flow pressure measurements was left
      shifted in NKCC2A-/- compared with wild-type mice, with maximum responses being
      significantly diminished. In summary, NKCC2A activity seems to be required for MD
      salt sensing in the high Cl concentration range. Coexpression of both high- and
      low-affinity isoforms of NKCC2 may permit transport and Cl-dependent
      tubuloglomerular feedback regulation to occur over a wider Cl concentration
      range.

PMID- 17215440
TI  - Antineutrophil cytoplasmic autoantibody-negative Pauci-immune crescentic
      glomerulonephritis.
AB  - Pauci-immune crescentic glomerulonephritis (CrGN) is one of the most common
      causes of rapidly progressive glomerulonephritis. The majority of patients with
      pauci-immune CrGN had circulating antineutrophil cytoplasmic autoantibody (ANCA).
      However, patients with ANCA-negative pauci-immune CrGN were not investigated
      fully. This study aimed to analyze the characteristics of this subgroup of
      patients. Patients whose pauci-immune CrGN was diagnosed from 1997 to 2006 in one
      center were studied retrospectively. The criteria of pauci-immune was defined as
      "the intensity of glomerular immunoglobulins staining by direct
      immunofluorescence assay in renal sections was negative to 1+ staining on a scale
      of 0 to 4+." Clinical and pathologic characteristics were compared between
      patients with and without ANCA. Among the 85 patients with pauci-immune CrGN, 28
      (32.9%) were ANCA negative. Compared with the 57 ANCA-positive patients, the ANCA
      negative patients were much younger (39.7 +/- 17.0 versus 57.6 +/- 14.0 yr; P <
      0.001). The level of urinary protein and the prevalence of nephrotic syndrome
      were significantly higher in ANCA-negative patients than that in ANCA-positive
      patients (P < 0.01 and P < 0.001, respectively). However, the prevalence of
      extrarenal involvement was significantly lower in ANCA-negative patients than
      that in ANCA-positive patients. The renal survival was poorer in ANCA-negative
      patients than that in ANCA-positive ones (P < 0.05). ANCA-negative pauci-immune
      CrGN was not rare and might represent an independent disease entity from ANCA
      positive vasculitis.

PMID- 17215441
TI  - Differences in 24-hour urine composition between black and white women.
AB  - Black women are less likely to develop kidney stones and have greater bone mass
      than white women. However, little is known about racial differences in urine
      composition. Urine pH, volume, and 24-h urinary excretion of calcium, citrate,
      oxalate, uric acid, sodium, potassium, magnesium, phosphate, sulfate, and
      creatinine of 146 black women were compared with 330 white women in the Nurses'
      Health Study. All participants were postmenopausal non-stone formers. ANOVA was
      used to compare mean urinary values. Linear regression models were adjusted for
      age, body mass index, dietary intake, and urinary factors. On average, black
      women excreted 65 mg less urinary calcium (P < 0.001), 4 mg more oxalate (P <
      0.001), 9 mEq less potassium (P < 0.001), 11 mg less magnesium (P = 0.003), 120
      mg less phosphate (P < 0.001), and 3 mmol less sulfate (P < 0.001) per day than
      did white women. The urine pH of black women was 0.11 units higher (P = 0.03) and
      urine volume was 0.24 L less (P = 0.001). The urinary relative supersaturations
      of calcium oxalate (P = 0.03) and brushite (P = 0.002) were lower in black women.
      No other significant differences were observed. Differences in urinary calcium
      and pH persisted after multivariate adjustment and after exclusion of
      participants who were taking thiazide diuretics or those with diabetes. In
      conclusion, black women excrete less urinary calcium and have a higher urinary pH
      than do white women. These differences are not explained by differences in age,
      body mass index, or diet and may account for the lower incidence of both
      nephrolithiasis and osteoporosis in black women.

PMID- 17215442
TI  - What predicts progression and regression of urinary albumin excretion in the
      nondiabetic population?
AB  - An increase or decrease in urinary albumin excretion (UAE) is associated with,
      respectively, a higher or lower risk for renal and cardiovascular disease,
      independent of widely known cardiovascular risk factors. This study aimed to
      identify factors that are associated with changes in UAE in the nondiabetic
      population using data of the Prevention of Renal and Vascular End stage Disease
      (PREVEND) Study, a community-based prospective cohort study. Data of the 6647
      nondiabetic participants who completed the first (1997 through 2001) and second
      (2001 through 2003) screening were used. Change in UAE was categorized as
      regression (n = 650), stable (n = 5240), or progression (n = 757) on the basis of
      change in class during follow-up, with classes being a UAE <15, 15 to 30, 30 to
      300, and >300 mg/24 h. With the use of stepwise forward multinomial regression
      analysis changes in BP, fasting glucose concentration, and start of
      antihypertensive drugs were found to be the most important modifiable variables
      associated with the risk for progression and regression (P < 0.01 for likelihood
      ratio test). The odds ratios to develop regression or progression of UAE during
      follow-up were 0.64 (95% confidence interval [CI] 0.57 to 0.73) and 1.91 (95% CI
      1.72 to 2.12), respectively, per 10-mmHg increase in BP during follow-up, 0.89
      (95% CI 0.80 to 0.98) and 1.09 (95% CI 1.01 to 1.17), respectively, per 1-mmol/L
      increase of fasting glucose levels during follow-up, and 1.57 (95% CI 1.21 to
      2.06) and 0.70 (95% CI 0.51 to 0.95), respectively, for start of antihypertensive
      drugs during follow-up. These associations were independent of baseline BP,
      glucose, body mass index, estimated GFR, and UAE and changes in high-sensitivity
      C-reactive protein during follow-up. In conclusion, changes in glucose
      concentration and BP and start of antihypertensive drugs (angiotensin-converting
      enzyme inhibitors/angiotensin receptor blockers in >50% of cases) are associated
      with progression and regression of UAE in the nondiabetic population. Although
      associations do not necessarily suggest causality, it is hypothesized that in the
      general population, the most important ways to reduce UAE are by lowering glucose
      concentration and BP (including start of antihypertensive medication), even in
      normotensive, nondiabetic individuals.

PMID- 17215443
TI  - Reduced systolic myocardial function in children with chronic renal
      insufficiency.
AB  - Increased left ventricular (LV) mass in children with chronic renal insufficiency
      (CRI) might be adaptive to sustain myocardial performance in the presence of
      increased loading conditions. It was hypothesized that in children with CRI, LV
      systolic function is impaired despite increased LV mass (LVM). Standard
      echocardiograms were obtained in 130 predialysis children who were aged 3 to 18
      yr (59% boys) and had stages II through IV chronic kidney disease and in 130
      healthy children of similar age, gender distribution, and body build. Systolic
      function was assessed by measurement of fractional shortening at the endocardial
      (eS) and midwall (mS) levels and computation of end-systolic stress (myocardial
      afterload). The patients with CRI exhibited a 6% lower eS (33.1 +/- 5.5 versus
      35.3 +/- 6.1%; P < 0.05) and 10% lower mS (17.8 +/- 3.1 versus 19.7 +/- 2.7%; P <
      0.001) than control subjects in the presence of significantly elevated BP,
      increased LVM, and more concentric LV geometry. Whereas the decreased eS was
      explained entirely by augmented end-systolic stress, mS remained reduced after
      correction for myocardial afterload. The prevalence of subclinical systolic
      dysfunction as defined by impaired mS was more than five-fold higher in patients
      with CRI compared with control subjects (24.6 versus 4.5%; P < 0.001). Systolic
      dysfunction was most common (48%) in patients with concentric hypertrophy and
      associated with lower hemoglobin levels. CRI in children is associated with
      impaired intrinsic LV contractility, which parallels increased LVM.

PMID- 17215444
TI  - P2Y1 gene deficiency protects from renal disease progression and capillary
      rarefaction during passive crescentic glomerulonephritis.
AB  - The metabotropic receptor P2Y1 is necessary for full ADP-induced platelet
      activation and is localized on various intrinsic renal cells, including mesangial
      cells, podocytes, and endothelial cells. To date, nothing is known about the role
      of the P2Y1 receptor during inflammatory renal disease. The role of the P2Y1
      receptor was investigated using 22 P2Y1 gene-deficient (-/-) and 27 wild-type
      (wt) mice during the time course of passive crescentic nephrotoxic
      glomerulonephritis. Six P2Y1 -/- and six wt mice served as undiseased controls.
      Renal tissues were harvested on days 1, 10, and 28 after disease induction. No
      renal phenotype was found in P2Y1 -/- versus wt mice. In contrast, during
      crescentic glomerulonephritis, approximately 50% of all wt mice died, whereas all
      P2Y1 -/- mice survived. Renal function as assessed by creatinine clearance
      measurements, glomerulosclerosis, and tubulointerstitial injury indices as well
      as glomerular and interstitial matrix expansion were improved significantly in
      P2Y1 -/- compared with wt mice. These changes were preceded by reduced glomerular
      and peritubular capillary rarefaction indices in P2Y1 -/- compared with wt mice.
      The alteration of the rates of both peritubular apoptosis and endothelial cell
      proliferation suggests improved capillary preservation in P2Y1 -/- mice early in
      disease (day 10) and an additional enhanced repair reaction in P2Y1 -/- mice at
      the late time point (day 28), whereas injury on day 1 seemed to be equivalent in
      both groups. It is concluded that loss of P2Y1 receptor function safeguards
      against capillary loss, fibrosis, and death by renal failure during experimental
      crescentic glomerulonephritis.

PMID- 17215445
TI  - Kidney function and risk of peripheral arterial disease: results from the
      Atherosclerosis Risk in Communities (ARIC) Study.
AB  - Chronic kidney disease (CKD) is associated with an increased risk for
      cardiovascular disease, but its association with peripheral arterial disease
      (PAD) is unclear. With the use of data from the Atherosclerosis Risk in
      Communities (ARIC) Study, 14,280 middle-aged adults were categorized on the basis
      of estimated GFR >/=90, 60 to 89, and 15 to 59 ml/min per 1.73 m(2) for normal
      kidney function, mildly decreased kidney function, and stages 3 to 4 CKD,
      respectively. Incident PAD was defined as a new onset of ankle-brachial index
      <0.9 assessed at regular examinations, new intermittent claudication assessed by
      annual surveillance, or PAD-related hospital discharges. Incidence rates and
      relative risks (RR) for PAD were compared across these categories. During a mean
      follow-up time of 13.1 yr (186,616 person-years), 1016 participants developed
      PAD. The incidence rates per 1000 person-years were 4.7, 4.9, and 8.6 for the
      normal kidney function, mildly decreased kidney function, and CKD groups,
      respectively. Compared with participants with normal kidney function, the age-,
      gender-, race-, and ARIC field center-adjusted RR for PAD was 1.04 (95%
      confidence interval [CI] 0.91 to 1.18) for those with mildly decreased kidney
      function and 1.82 (95% CI 1.34 to 2.47) for those with CKD. After additional
      adjustment for cardiovascular disease risk factors, an increase in risk for
      incident PAD still was observed in participants with CKD, with a multivariable
      adjusted RR of 1.56 (95% CI 1.13 to 2.14). Patients with CKD are at increased
      risk for incident PAD. Development of strategies for screening and prevention of
      PAD in this high-risk population seems warranted.

PMID- 17215447
TI  - GABAB receptor-positive modulation-induced blockade of the rewarding properties
      of nicotine is associated with a reduction in nucleus accumbens DeltaFosB
      accumulation.
AB  - There is an increasing demand for a novel non-nicotinic, nondopaminergic
      therapeutic approach to nicotine addiction. GABAergic mechanisms have been
      implicated in drug dependence. Recently, a novel GABAB receptor allosteric
      positive modulator, GS39783, was characterized. There are no investigations to
      date on the effects of GABAB receptor-positive modulators in animal models of
      nicotine reinforcement. Conditioned place preference (CPP) paradigms are based on
      the principle that animals, like humans, would learn to seek environmental
      stimuli that have been previously associated with rewarding events. Here we show
      that nicotine (0.06 mg/kg s.c.) induced a robust CPP response. Furthermore,
      GS39783 (30-100 mg/kg p.o.) during the conditioning phase blocked the rewarding
      effects of nicotine in the CPP paradigm in rats. However, GS39783 did not
      significantly alter the CPP effects of nicotine when given only immediately
      before the CPP test. A growing body of evidence suggests that repeated
      administration of drugs of abuse induced long-term molecular changes in brain
      plasticity, most notably an accumulation of DeltaFosB, in the striatal complex
      that contribute to the manifestation of dependence. There was a significant
      accumulation of DeltaFosB in the nucleus accumbens, but not in the dorsal
      striatum, of rats treated daily for 5 days with nicotine (0.06 mg/kg i.p.).
      GS39783 completely (30-100 mg/kg p.o.) counteracted these nicotine-induced
      molecular adaptations when given before the CPP acquisition phase but not when
      administered immediately before the test phase. Taken together, the behavioral
      and molecular changes induced by nicotine occur in concert and are concomitantly
      amenable to reversal by GABAB receptor-positive modulators.

PMID- 17215446
TI  - Chronic activation of peroxisome proliferator-activated receptor-alpha with
      fenofibrate prevents alterations in cardiac metabolic phenotype without changing
      the onset of decompensation in pacing-induced heart failure.
AB  - Severe heart failure (HF) is characterized by profound alterations in cardiac
      metabolic phenotype, with down-regulation of the free fatty acid (FFA) oxidative
      pathway and marked increase in glucose oxidation. We tested whether fenofibrate,
      a pharmacological agonist of peroxisome proliferator-activated receptor-alpha,
      the nuclear receptor that activates the expression of enzymes involved in FFA
      oxidation, can prevent metabolic alterations and modify the progression of HF. We
      administered 6.5 mg/kg/day p.o. fenofibrate to eight chronically instrumented
      dogs over the entire period of high-frequency left ventricular pacing (HF +
      Feno). Eight additional HF dogs were not treated, and eight normal dogs were used
      as a control. [3H]Oleate and [14C]Glucose were infused intravenously to measure
      the rate of substrate oxidation. At 21 days of pacing, left ventricular end
      diastolic pressure was significantly lower in HF + Feno (14.1 +/- 1.6 mm Hg)
      compared with HF (18.7 +/- 1.3 mm Hg), but it increased up to 25 +/- 2 mm Hg,
      indicating end-stage failure, in both groups after 29 +/- 2 days of pacing. FFA
      oxidation was reduced by 40%, and glucose oxidation was increased by 150% in HF
      compared with control, changes that were prevented by fenofibrate. Consistently,
      the activity of myocardial medium chain acyl-CoA dehydrogenase, a marker enzyme
      of the FFA beta-oxidation pathway, was reduced in HF versus control (1.46 +/-
      0.25 versus 2.42 +/- 0.24 micromol/min/gram wet weight (gww); p < 0.05) but not
      in HF + Feno (1.85 +/- 0.18 micromol/min/gww; N.S. versus control). Thus,
      preventing changes in myocardial substrate metabolism in the failing heart causes
      a modest improvement of cardiac function during the progression of the disease,
      with no effects on the onset of decompensation.

PMID- 17215448
TI  - The glycocalyx protects erythrocyte-bound tissue-type plasminogen activator from
      enzymatic inhibition.
AB  - Coupling tissue-type plasminogen activator (tPA) to carrier red blood cells (RBC)
      prolongs its intravascular life span and permits its use for thromboprophylaxis.
      Here, we studied the susceptibility of RBC/tPA to PA inhibitors including
      plasminogen activator inhibitor-1 (PAI-1) that constrain its activity and may
      reduce the duration of its effect. Despite lesser spatial and diffusional
      limitations, soluble tPA was far less effective than RBC/tPA in dissolving clots
      formed in vitro from blood of wild-type (WT) mice (40 versus 80% lysis at equal
      doses of tPA). Furthermore, after i.v. injection, soluble tPA lost activity
      faster in transgenic mice expressing a high level of PAI-1 than in WT mice,
      whereas the activity of RBC/tPA was unaffected. PAI-1 inactivated soluble tPA at
      equimolar ratios in vitro, but it had no effect on the amidolytic or fibrinolytic
      activity of RBC/tPA. RBC/tPA was also more resistant than soluble tPA to in vitro
      inhibition by other serpins (alpha2-macroglobulin and alpha1-antitrypsin) and
      pathologically high levels of glucose. However, coupling to RBC did not protect a
      truncated tPA mutant, Retavase, from plasma inhibitors. Chemical removal of the
      RBC glycocalyx negated tPA protection from inhibitors: tPA coupled to glycocalyx
      stripped RBC bound twice as much 125I-PAI-1 as did tPA coupled to naive RBC, and
      susceptibility of the bound tPA to inhibition by PAI-1 was restored. Thus, the
      RBC glycocalyx protects RBC-coupled tPA against inhibition. Resistance to high
      levels of inhibitors in vivo contributes to the potential utility of RBC/tPA for
      thromboprophylaxis.

PMID- 17215449
TI  - Transmitting on actin: synaptic control of dendritic architecture.
AB  - Excitatory synaptic transmission in the central nervous system mainly takes place
      at dendritic spines, highly motile protrusions on the dendritic surface.
      Depending on the stimuli received, dendritic spines undergo rapid actin-based
      changes in their morphology. This plasticity appears to involve signaling through
      numerous proteins that control the organization of the actin cytoskeleton (actin
      regulators). At least in part, recruitment and activation of these depends on
      neurotransmitter receptors at the post-synapse, which directly link
      neurotransmission to changes in dendritic spine architecture. However, other, non
      neurotransmitter-receptors present at dendritic spines also participate. It is
      likely that several receptor types can control the activity of a single actin
      regulatory pathway and it is the complex integration of numerous signals that
      determines the overall architecture of a dendritic spine.

PMID- 17215450
TI  - Beta-arrestin signaling and regulation of transcription.
AB  - Beta-arrestin 1 and beta-arrestin 2 are well-known negative regulators of G
      protein-coupled receptor (GPCR) signaling. Upon GPCR activation, beta-arrestins
      translocate to the cell membrane and bind to the agonist-occupied receptors. This
      uncouples these receptors from G proteins and promotes their internalization,
      thus causing desensitization. However, accumulating evidence indicates that beta
      arrestins also function as scaffold proteins that interact with several
      cytoplasmic proteins and link GPCRs to intracellular signaling pathways such as
      MAPK cascades. Recent work has also revealed that, in response to activation of
      certain GPCRs, beta-arrestins translocate from the cytoplasm to the nucleus and
      associate with transcription cofactors such as p300 and cAMP-response element
      binding protein (CREB) at the promoters of target genes to promote transcription.
      They also interact with regulators of transcription factors, such as IkappaBalpha
      and MDM2, in the cytoplasm and regulate transcription indirectly. This beta
      arrestin-mediated regulation of transcription appears to play important roles in
      cell growth, apoptosis and modulation of immune functions.

PMID- 17215451
TI  - BAD-LAMP defines a subset of early endocytic organelles in subpopulations of
      cortical projection neurons.
AB  - The brain-associated LAMP-like molecule (BAD-LAMP) is a new member of the family
      of lysosome associated membrane proteins (LAMPs). In contrast to other LAMPs,
      which show a widespread expression, BAD-LAMP expression in mice is confined to
      the postnatal brain and therein to neuronal subpopulations in layers II/III and V
      of the neocortex. Onset of expression strictly parallels cortical synaptogenesis.
      In cortical neurons, the protein is found in defined clustered vesicles, which
      accumulate along neurites where it localizes with phosphorylated epitopes of
      neurofilament H. In primary neurons, BAD-LAMP is endocytosed, but is not found in
      classical lysosomal/endosomal compartments. Modification of BAD-LAMP by addition
      of GFP revealed a cryptic lysosomal retention motif, suggesting that the
      cytoplasmic tail of BAD-LAMP is actively interacting with, or modified by,
      molecules that promote its sorting away from lysosomes. Analysis of BAD-LAMP
      endocytosis in transfected HeLa cells provided evidence that the protein recycles
      to the plasma membrane through a dynamin/AP2-dependent mechanism. Thus, BAD-LAMP
      is an unconventional LAMP-like molecule and defines a new endocytic compartment
      in specific subtypes of cortical projection neurons. The striking correlation
      between the appearance of BAD-LAMP and cortical synatogenesis points towards a
      physiological role of this vesicular determinant for neuronal function.

PMID- 17215452
TI  - Limit Ketek to pneumonia, experts advise: advisers urge black-box warning.

PMID- 17215454
TI  - High performing? Innovative? North Mississippi has proof.

PMID- 17215453
TI  - Antidepressant black-box warning should include young adults, panel urges.

PMID- 17215456
TI  - Many Americans dislike consumer-directed health coverage.

PMID- 17215457
TI  - Compliance with guidelines for treating sepsis.

PMID- 17215458
TI  - Missed opportunity for stem-cell research.

PMID- 17215459
TI  - Virtual strategic planning.

PMID- 17215461
TI  - Concerns about study on Beers criteria.

PMID- 17215462
TI  - Conscientious objection: a pharmacist's right or professional negligence?

PMID- 17215463
TI  - Pharmacy leadership structure in a multicampus health system.

PMID- 17215464
TI  - Adopting health care informatics and technologies.

PMID- 17215465
TI  - Are we prepared?

PMID- 17215466
TI  - Avian influenza: a review.
AB  - PURPOSE: A review of the avian influenza A/H5N1 virus, including human cases,
      viral transmission, clinical features, vaccines and antivirals, surveillance
      plans, infection control, and emergency response plans, is presented. SUMMARY:
      The World Health Organization (WHO) considers the avian influenza A/H5N1 virus a
      public health risk with pandemic potential. The next human influenza pandemic, if
      caused by the avian influenza A/H5N1 virus, is estimated to have a potential
      mortality rate of more than a hundred million. Outbreaks in poultry have been
      associated with human transmission. WHO has documented 258 confirmed human
      infections with a mortality rate greater than 50%. Bird-to-human transmission of
      the avian influenza virus is likely by the oral-fecal route. The most effective
      defense against an influenza pandemic would be a directed vaccine to elicit a
      specific immune response toward the strain or strains of the influenza virus.
      However, until there is an influenza pandemic, there is no evidence that vaccines
      or antivirals used in the treatment or prevention of such an outbreak would
      decrease morbidity or mortality. Surveillance of the bird and human populations
      for the highly pathogenic H5N1 is being conducted. Infection-control measures and
      an emergency response plan are discussed. CONCLUSION: Avian influenza virus
      A/H5N1 is a public health threat that has the potential to cause serious illness
      and death in humans. Understanding its pathology, transmission, clinical
      features, and pharmacologic treatments and preparing for the prevention and
      management of its outbreak will help avoid its potentially devastating
      consequences.

PMID- 17215467
TI  - Identifying drugs needing pharmacogenetic monitoring in a Korean hospital.
AB  - PURPOSE: A decision matrix for identifying drugs for which pharmacogenetic drug
      monitoring (PDM) provides the greatest benefit in a Korean setting is described.
      SUMMARY: We developed a decision matrix including the ethnic frequency of
      clinically relevant polymorphic cytochrome P-450 (CYP) enzymes, and the metabolic
      profiles and adverse drug reactions of drugs. Using the developed decision matrix
      based on the population allele frequencies of CYP enzymes, we identified
      potential candidates for PDM among the most commonly used drugs at Seoul National
      University Hospital (SNUH). Collectively, 17 of these drugs were largely
      metabolized by at least one polymorphic CYP enzyme. Pharmacogenetic information
      was used to identify CYP2C9, CYP2C19, and CYP2D6 as the major CYP enzymes of
      clinical importance for pharmacologic effect and safety in Koreans. The
      frequencies of poor and intermediate metabolizers among Koreans were 0% and 2.3
      12% for CYP2C9, 12% and 42% for CYP2C19, and 0.44% and 28% for CYP2D6,
      respectively. The frequency of ultrarapid metabolizers of CYP2D6 was 2.28%. The
      decision matrix and pharmacogenetic information were used to identify seven drugs
      for PDM: warfarin, glimepiride, diazepam, amitriptyline, nortriptyline, codeine,
      and oxycodone. This approach can be applied to other institutional hospitals or
      other ethnic populations and would be helpful for advancing pharmacy practice.
      Further work is required to assess the practical and potential clinical relevance
      of pharmacogenetic variations on drugs of interest before the implementation of
      PDM. CONCLUSION: A decision matrix helped identify drugs for which PDM provides
      the greatest potential benefit at one Korean hospital.

PMID- 17215468
TI  - Interrater agreement with a standard scheme for classifying medication errors.
AB  - PURPOSE: The interrater agreement for and reliability of the National
      Coordinating Council for Medication Error Reporting and Prevention (NCC MERP)
      index for categorizing medication errors were determined. METHODS: A letter was
      sent by the U.S. Pharmacopeia to all 550 contacts in the MEDMARX system user
      database. Participants were asked to categorize 27 medication scenarios using the
      NCC MERP index and were randomly assigned to one of three tools (the index alone,
      a paper-based algorithm, or a computer-based algorithm) to assist in
      categorization. Because the NCC MERP index accounts for harm and cost, and
      because categories could be interpreted as substantially similar, study results
      were analyzed after the nine error categories were collapsed to six. The
      interrater agreement was measured using Cohen's kappa value. RESULTS: Of 119
      positive responses, 101 completed surveys were returned for a response rate of
      85%. There were no significant differences in baseline demographics among the
      three groups. The overall interrater agreement for the participants, regardless
      of group assignment, was substantial at 0.61 (95% confidence interval [CI], 0.41
      0.81). There was no difference among the kappa values of the three study groups
      and the tools used to aid in medication error classification. When the index was
      condensed from nine categories to six, the interrater agreement increased with a
      kappa value of 0.74 (95% CI, 0.56-0.90). CONCLUSION: Overall interrater agreement
      for the NCC MERP index for categorizing medication errors was substantial. The
      tool provided to assist with categorization did not influence overall
      categorization. Further refining of the scale could improve the usefulness and
      validity of medication error categorization.

PMID- 17215469
TI  - Evaluation of conflicting literature and application to formulary decisions.
AB  - PURPOSE: Guidelines were developed for grading the quality, quantity, and
      consistency of drug literature in support of formulary recommendations. METHODS:
      Four developmental steps were taken to create a comprehensive literature
      evaluation system. The first step identified the attributes of a body of
      literature that were most reflective of its applicability to patient care. The
      next step defined each domain (quality, quantity, consistency), as determined by
      the Agency of Healthcare Research and Quality (AHRQ), in terms of the specific
      qualities to be assessed; a value was assigned to those qualities. Also, a
      literature search was conducted to identify strategies for evaluating bodies of
      literature employed in published assessment tools. Following the analysis of
      previously published systems, which were evaluated with respect to their
      inclusion of the AHRQ-identified domains, the next step was the development of
      specific domains and definitions to get a composite grade (with "better" evidence
      earning more points) for formulary recommendations. The final step was the
      creation of a system that aggregated the final score for the recommendation. The
      recommendation was categorized according to quality, quantity, and consistency of
      supporting evidence, and the total number of points was calculated and the
      recommendation given letter and numerical grades. RESULTS: The guidelines that
      were developed allow the user to accurately, consistently, and easily determine
      the strength of recommendations for a body of literature that may be conflicting.
      The addition of criteria for quantity and consistency to previously-published
      grading systems has made the guidelines more objective. CONCLUSION: A system that
      accounts for the quality, quantity, and consistency of drug literature was
      developed to assist in making formulary decisions.

PMID- 17215470
TI  - Basic terminology in obtaining reimbursement for pharmacists' cognitive services.
AB  - PURPOSE: A basic overview and definitions of commonly used billing and
      reimbursement terminology that pharmacists will need to know to obtain
      reimbursement for cognitive services are provided. SUMMARY: Currently, the
      profession of pharmacy has been gathering momentum in its efforts to seek and
      obtain reimbursement for cognitive services. However, there have been major
      barriers in seeking reimbursement, including the lack of understanding by third
      party payers of the pharmacist's role in patient care and the pharmacist's in
      depth knowledge of pharmacotherapy, the lack of appropriate billing codes for
      pharmacists' services, and the lack of detailed knowledge and understanding by
      pharmacy practitioners of nondistributive reimbursement mechanisms, processes,
      and terminology. The types of services provided are usually described by the
      American Medical Association's Current Procedural Terminology (CPT) codes for the
      face-to-face provision of patient care services by a pharmacist. As of January 1,
      2006, pharmacists have been able to indicate the appropriate diagnosis code from
      the International Classification of Diseases, 9th Revision (ICD-9) (ICD-10 will
      replace the ICD-9 on October 1, 2007), and CPT code when billing under a major
      medical plan that recognizes the pharmacist as a patient care service provider.
      Understanding the billing and reimbursement terminology will aid pharmacist
      communication with third-party payers, Medicare, and Medicaid. A glossary of the
      most commonly encountered terms in billing and reimbursement procedures for
      cognitive services is provided. Also included are lists of Web-based
      reimbursement resources and references on reimbursement for cognitive services by
      the pharmacist. CONCLUSION: An understanding of terminology is important in
      receiving reimbursement for cognitive services.

PMID- 17215471
TI  - Implementing the Medicare drug benefit in a diverse inner-city community.
AB  - PURPOSE: An integrated effort to maintain continued access to pharmacy services
      and prescribed medications for patients in an inner-city community before and
      during the implementation of the Medicare prescription drug benefit is described.
      SUMMARY: An academic medical center and college of pharmacy in a culturally
      diverse, inner-city Chicago community created a strategy to provide uninterrupted
      pharmacy services to all of their Medicare Part D eligible patients, particularly
      those dual eligible for Medicaid and Medicare, during the transition from
      Medicaid to Medicare Part D, effective January 1, 2006. The percentage of dual
      eligible patients in the Medicare Part D eligible population at the institution
      was more than twice the national average. A task force was created to prepare for
      the onset of Medicare Part D. The task force had goals in three areas: education,
      outreach, and operations; it was also responsible for the development of a
      contingency plan for any problems that could happen after January 1. A Medicare
      drug benefit consult service was formed to ensure that Medicare eligible patients
      understood the Medicare drug benefit and received customized assistance. Although
      problems were encountered, the investment in the preparation and implementation
      of the Medicare drug benefit, especially the consult service, resulted in a
      positive return on the institution's investment. Suggestions for other
      institutions facing the challenge of the implementation of the Medicare drug
      benefit are provided. CONCLUSION: Implementing a federal-level program among a
      diverse subset of patients is challenging and requires concerted efforts from
      health care providers and support from the institution. The Medicare drug benefit
      task force at the institution assumed responsibility for all pharmacy activities
      related to Medicare Part D and achieved its goals in education, outreach, and
      operations. This resulted in continued access to pharmacy services and prescribed
      medications for patients.

PMID- 17215472
TI  - Overview of Medicare Part D prescription drug benefit: potential implications for
      patients with psychotic disorders.
AB  - PURPOSE: Medicare Part D prescription drug benefits are reviewed. Potential
      implications for patients with psychotic disorders in relation to Medicare Part D
      are discussed. SUMMARY: The newly created Medicare Part D provides prescription
      drug benefits to many individuals formerly without prescription benefits and,
      possibly, lower-cost benefits to those who previously relied on other benefits.
      Participating prescription plans use a variety of pharmacy management tools to
      minimize costs while providing benefit plans that meet Part D requirements for
      composition and coverage. Patients then have the challenge of choosing a
      prescription drug plan that will best satisfy their prescriptions needs.
      CONCLUSION: The rollout of Part D has not been without problems, and although
      more Medicare participants are receiving prescription drug benefits at a greater
      savings, there are concerns that Part D may not provide adequate coverage for all
      patients or for patients requiring certain types of medications, especially some
      psychotropic medications. Pharmacists have voiced concerns about the Medicare
      Part D drug plan in regard to both the degree of coverage it provides to
      enrollees and the difficulty in administering the benefit.

PMID- 17215475
TI  - Differential pharmacology of atypical antipsychotics: clinical implications.
AB  - PURPOSE: Pharmacology of atypical antipsychotics and the clinical implications
      are reviewed. SUMMARY: Psychiatric disorders, such as schizophrenia and bipolar
      disorder, are often associated with poor outcomes. Atypical antipsychotics have
      become the standard of care for these disorders, and multiple agents have
      demonstrated efficacy for both acute and maintenance therapy. As a result of
      their differential pharmacologic properties, atypical antipsychotics have diverse
      clinical profiles, resulting in different liabilities for specific adverse
      events. These effects can, in turn, have an adverse impact on patient
      functionality, adherence to therapy, and overall health. CONCLUSION: Atypical
      antipsychotics have distinct pharmacological profiles which result in clinically
      meaningful differences in adverse effects. Clinicians should have a wide choice
      of agents available with which to optimize outcomes in the majority of patients
      with psychiatric disorders.

PMID- 17215476
TI  - Pharmacotherapy for behavioral and psychological symptoms of dementia in the
      elderly.
AB  - PURPOSE: The use of atypical antipsychotics for maximizing clinical efficacy and
      overall health in patients with neuropsychiatric symptoms of dementia is
      discussed. SUMMARY: Psychotic and behavioral symptoms are common among older
      patients with dementia, and an accurate diagnosis can be obscured by complex
      presentation of symptoms and comorbidities. When initiating pharmacotherapy in
      this patient population, it is important to consider the increased presence of
      comorbidities and the additive pharmacologic effects of concomitantly
      administered drugs. Atypical antipsychotics are among the most well-studied
      therapeutic classes of psychoactive medications and are frequently utilized for
      treating psychotic symptoms and agitation in the elderly. These medications have
      distinct pharmacologic profiles with different liabilities for adverse effects
      such as sedation, metabolic disturbances, and anticholinergic effects. Recent
      findings from the Clinical Antipsychotic Trials of Intervention Effectiveness
      Alzheimer's Disease (CATIE-AD) study demonstrate that although these agents have
      some efficacy, their adverse effects may limit their utility in patients.
      CONCLUSION: The adverse effect profile should be an important consideration for
      clinicians selecting an atypical antipsychotic for use in this population.

PMID- 17215477
TI  - The morphology of the koniocellular axon pathway in the macaque monkey.
AB  - The key objective of this study was to determine the distribution and morphology
      of koniocellular (K) lateral geniculate nucleus (LGN) axons in primary visual
      cortex (V1) of the macaque monkey. In particular, we were interested in
      understanding whether subpopulations of K axons exist in this species and, if so,
      if these subpopulations arise from different K layers of the LGN. Restricted
      injections of the tracers, biotinilated dextran amine, or Phaseolus vulgaris
      leucoagglutinin were targeted to specific LGN K layers under electrophysiological
      guidance and immunocytochemistry was used to visualize labeled axons in cortex
      that were subsequently reconstructed through serial sections. A total of 36
      complete axons and 166 axon segments were reconstructed. Our results identified
      at least 2 main subpopulations of K axons in macaque V1 based on branching
      patterns and bouton distribution. Axons that arise primarily from LGN layers K1
      and K2 are morphologically simple and tend to branch in cortical layers 1 and 3A.
      These axons give rise to fewer boutons than seen in axons arising from the dorsal
      K LGN layers K3-K6. Axons that arise from LGN layers K3-K6 terminate as complex,
      focused arbors in the cytochrome oxidase (CO) blobs in layer 3Balpha, with only
      occasional simple projections to the more superficial layers of cortex. Combined
      with previous observations, our data suggest that there are at least 3 subclasses
      of K LGN axons in macaque monkey that are similar to K axons identified earlier
      in both nocturnal simian owl monkeys (Ding and Casagrande 1997) and in prosimian,
      bush babies (Lachica and Casagrande 1992) suggesting that the LGN K channels that
      terminate in the CO blobs and in layer 1 are not unique to macaque monkeys but
      are a common primate feature.

PMID- 17215478
TI  - Human parietal "reach region" primarily encodes intrinsic visual direction, not
      extrinsic movement direction, in a visual motor dissociation task.
AB  - Posterior parietal cortex (PPC) participates in the planning of visuospatial
      behaviors, including reach movements, in gaze-centered coordinates. It is not
      known if these representations encode the visual goal in retinal coordinates, or
      the movement direction relative to gaze. Here, by dissociating the intrinsic
      retinal stimulus from the extrinsic direction of movement, we show that PPC
      employs a visual code. Using delayed pointing and event-related functional
      magnetic resonance imaging, we identified a cluster of PPC regions whose activity
      was topographically (contralaterally) related to the direction of the planned
      movement. We then switched the normal visual-motor spatial relationship by
      adapting subjects to optical left/right reversing prisms. With prisms, movement
      related PPC topography reversed, remaining tied to the retinal image. Thus,
      remarkably, the PPC region in each hemisphere now responded more for planned
      ipsilateral pointing movements. Other non-PPC regions showed the opposite world-
      or motor-fixed pattern. These findings suggest that PPC primarily encodes not
      motor commands but movement goals in visual coordinates.

PMID- 17215479
TI  - Prison tattoo program wasn't given enough time.

PMID- 17215480
TI  - Molecular determinants for the recruitment of the ubiquitin-ligase MuRF-1 onto M
      line titin.
AB  - Titin forms an intrasarcomeric filament system in vertebrate striated muscle,
      which has elastic and signaling properties and is thereby central to
      mechanotransduction. Near its C-terminus and directly preceding a kinase domain,
      titin contains a conserved pattern of Ig and FnIII modules (Ig(A168)-Ig(A169)
      FnIII(A170), hereby A168-A170) that recruits the E3 ubiquitin-ligase MuRF-1 to
      the filament. This interaction is thought to regulate myofibril turnover and the
      trophic state of muscle. We have elucidated the crystal structure of A168-A170,
      characterized MuRF-1 variants by circular dichroism (CD) and SEC-MALS, and
      studied the interaction of both components by isothermal calorimetry, SPOTS
      blots, and pull-down assays. This has led to the identification of the molecular
      determinants of the binding. A168-A170 shows an extended, rigid architecture,
      which is characterized by a shallow surface groove that spans its full length and
      a distinct loop protrusion in its middle point. In MuRF-1, a C-terminal helical
      domain is sufficient to bind A168-A170 with high affinity. This helical region
      predictably docks into the surface groove of A168-A170. Furthermore, pull-down
      assays demonstrate that the loop protrusion in A168-A170 is a key mediator of
      MuRF-1 recognition. Our findings indicate that this region of titin could serve
      as a target to attempt therapeutic inhibition of MuRF-1-mediated muscle turnover,
      where binding of small molecules to its distinctive structural features could
      block MuRF-1 access.

PMID- 17215481
TI  - Annexin 1: the new face of an old molecule.
AB  - The annexin superfamily consists of 13 calcium or calcium and phospholipid
      binding proteins with a significant degree of biological and structural homology
      (40-60%). First described in the late 1970s and subsequently referred to as
      macrocortin, renocortin, lipomodulin, lipocortin-1, and more recently Annexin 1,
      this 37 kDa calcium and phospholipid binding protein is a strong inhibitor of
      glucocorticoid-induced eicosanoid synthesis and PLA2. Recent interest in the
      biological activity of this intriguing molecule has unraveled important
      functional attributes of Annexin 1 in a variety of inflammatory pathways, on cell
      proliferation machinery, in the regulation of cell death signaling, in phagocytic
      clearance of apoptosing cells, and most importantly in the process of
      carcinogenesis. Here we attempt to present a short review on these diverse
      biological activities of an interesting and important molecule, which could be a
      potential target for novel therapeutic intervention in a host of disease states.

PMID- 17215482
TI  - The activated glucocorticoid receptor inhibits the transcription factor T-bet by
      direct protein-protein interaction.
AB  - Glucocorticoids (GCs) immunosuppression acts via regulation of several
      transcription factors (TF), including activating protein (AP)-1, NF-kappaB, and
      NFAT. GCs inhibit Th1 cytokines and promote a shift toward Th2 differentiation.
      Th1 phenotype depends on TF T-bet. In this study, we examined GC regulation of T
      bet. We found that GCs inhibit T-bet transcriptional activity. We show that
      glucocorticoid receptor (GR) physically interacts with T-bet both in transfected
      cell lines and in primary splenocyte cultures with endogenous GR and T-bet. This
      interaction also blocks GR-dependent transcription. We show both in vitro and in
      vivo at endogenous binding sites that the mechanism underlying T-bet inhibition
      further involves reduction of T-bet binding to DNA. Using specific mutations of
      GR, we demonstrate that the first zinc finger region of GR is required for T-bet
      inhibition. GCs additionally inhibit T-bet both at mRNA and protein expression
      levels, revealing another layer of GR action on T-bet. Finally, we examined the
      functional consequences of GR/T-bet interaction on IFN-gamma, showing that GCs
      inhibit transcriptional activity of T-bet on its promoter. In view of the crucial
      role of T-bet in T cell differentiation and inflammation, we propose that GR
      inhibitory interaction with T-bet may be an important mechanism underlying the
      immunosuppressive properties of GCs.

PMID- 17215483
TI  - Erythrocytes store and release sphingosine 1-phosphate in blood.
AB  - The blood constituent sphingosine 1-phosphate (S1P) is a specific ligand for five
      G-protein-coupled receptors designated S1P(1-5). Expression of the S1P1 receptor
      on lymphocytes is required for their exit from secondary lymphoid organs,
      suggesting that S1P serves as a stimulus for maintaining lymphocyte circulation
      in blood. Despite its potential role in immune surveillance, the regulatory
      system that controls blood S1P levels is not well understood. This report reveals
      that erythrocytes constitute a buffer system for S1P in blood. They efficiently
      incorporated and stored S1P, and protected it from cellular degradation. They
      also released S1P into plasma, but not into other serum-free media, indicating
      that S1P release was controlled by a plasma factor. Erythrocytes did not generate
      S1P since an increase in plasma S1P levels was always accompanied by a decrease
      in cellular S1P levels. Thrombocytes that were reported to generate and release
      S1P after activation did not contribute to the observed S1P release in blood. The
      amount of erythrocytes as well as the proportion of plasma in the medium
      determined the magnitude of S1P release. Adoptively transferred S1P-loaded and
      unloaded mouse erythrocytes displayed a normal life span and similar S1P levels
      24 h after recovery, indicating that S1P incorporation and release are
      dynamically regulated in vivo.

PMID- 17215484
TI  - Inhibition of a protein-protein interaction between INI1 and c-Myc by small
      peptidomimetic molecules inspired by Helix-1 of c-Myc: identification of a new
      target of potential antineoplastic interest.
AB  - c-Myc is a transcription modulator proto-oncogene. When overexpressed, it becomes
      an important contributor to the multi-hit process of malignant transformation. In
      two earlier papers in this journal (see refs. 19 , 20) we reported that retro
      inverso peptidomimetic molecules inspired by the Helix-1 of c-Myc motif could be
      sequence-specific antiproliferative agents active in the low micromolar range. We
      also found that our peptides were not opening the four-alpha-helix Myc:Max
      bundle. Their antiproliferative activity in cancer cell lines needs the presence
      of side chains projecting outside of the bundle in the corresponding native H1
      motif. This observation suggested interference with an external partner. In this
      study we investigated the INI1:Myc interaction. INI1 is a subunit of the SWI/SNF
      complex (component of the enhanceosome surrounding Myc:Max heterodimer). The
      INI1:Myc interaction was confirmed via pull down, ELISA, and fluorescence
      anisotropy assays. According to the length of INI1 fragments used, we calculated
      Kds ranging between 1.3x10(-6) and 4.8x10(-7) M. The three different techniques
      applied showed that the INI1:Myc interaction was also the target of our retro
      inverso peptidomimetic molecules, which seem to bind specifically at INI1. A Myc
      binding, 21aa INI1 fragment (minimum interacting sequence), could inspire the
      synthesis of a new class of more selective c-Myc inhibitors.

PMID- 17215485
TI  - Impaired respiration is positively correlated with decreased life span in
      Caenorhabditis elegans models of Friedreich Ataxia.
AB  - Impaired expression of mitochondrial genes causes alterations in life span of the
      nematode Caenorhabditis elegans. Intriguingly, although some of these genes have
      been shown to extend life expectancy and reduce aging processes, others are known
      to shorten life span in the same model organism. Reduced expression of a
      mitochondrial protein called frataxin causes a neurodegenerative disorder named
      Friedreich Ataxia, which decreases life span in humans. Surprisingly, reduced
      expression of the C. elegans frataxin homologue frh-1 has been associated with
      both increased as well as decreased life span by different laboratories. To
      further elucidate these conflicting findings, here we show that different RNA
      interference (RNAi) constructs directed against frh-1 reduce C. elegans life
      span. Moreover, we show that frh-1-inhibiting RNAi impairs oxygen consumption and
      that respiratory rate is positively correlated with life span in this
      multicellular eukaryote (r=0.8566), suggesting that >73% of life span variance in
      C. elegans is explained by changes in respiratory rate. Taken together, impaired
      mitochondrial metabolism due to RNAi-mediated inhibition of the frataxin
      homologue frh-1 causes both impaired respiration as well as decreased life span
      in the multicellular eukaryote C. elegans.

PMID- 17215486
TI  - Impairment of innate immune killing mechanisms by bacteriostatic antibiotics.
AB  - Antibiotics are designed to support host defense in controlling infection. Here
      we describe a paradoxical inhibitory effect of bacteriostatic antibiotics on key
      mediators of mammalian innate immunity. When growth of species including
      Escherichia coli and Staphylococcus aureus is suppressed by chloramphenicol or
      erythromycin, the susceptibility of the bacteria to cathelicidin antimicrobial
      peptides or serum complement was markedly diminished. Survival of the bacteria in
      human whole blood, human wound fluid, or a mouse wound infection model was in
      turn increased after antibiotic-induced bacteriostasis. These findings provide a
      further rationale against the indiscriminate use of antibiotics.

PMID- 17215487
TI  - Polymeric meshes induce zonal regulation of matrix metalloproteinase-2 gene
      expression by macrophages and fibroblasts.
AB  - Matrix metalloproteinase-2 (MMP-2) is a key regulator in wound healing that
      orchestrates tissue remodeling. In the present study the spatial and temporal
      distribution of MMP-2 gene transcription, protein synthesis, and enzymatic
      activity were analyzed following polymeric mesh (polyglactin, polypropylene)
      implantation in transgenic reporter mice harboring MMP-2 regulatory sequences 
      1686/+423 or -1241/+423. Polymers induced MMP-2 promoter activity in macrophages
      within the foreign body granuloma via sequences -1686/+423 with concomitantly up
      regulated protein synthesis and enzymatic activity. Macrophages distant from mesh
      filaments exhibited low MMP-2 expression levels. Fibroblasts surrounding mesh
      material displayed strong MMP-2 gene transcription independent of the included
      promoter sequences, whereas fibroblasts without close contact to mesh material
      had low MMP-2 synthesis rates due to silencing activity of sequences -1686/-1241.
      In vitro studies support a cellular crosstalk concept, as macrophages trans
      repressed MMP-2 gene transcription in fibroblasts. The zonal and cell-specific
      regulation of MMP-2 gene transcription illuminates an intimate cellular crosstalk
      in foreign body reaction that may provide a new approach for mesh modification.

PMID- 17215488
TI  - In vitro gamete derivation from pluripotent stem cells: progress and perspective.
AB  - Germ cells constitute a highly specialized cell population that is indispensable
      for the continuation and evolution of the species. Recently, several research
      groups have shown that these unique cells can be produced in vitro from
      pluripotent stem cells. Furthermore, live births of offspring using induced germ
      cells have been reported in one study. These results suggest that it may be
      possible to investigate germ cell development ex vivo and to establish novel
      reproductive technologies. To this end, it is critical to assess if gamete
      induction processes in vitro faithfully recapitulate normal germ cell development
      in vivo. Here, this issue is discussed with a focus on the germ line
      specification and the sex-specific development of pre- and postnatal germ cells.
      The aim of this paper is to concisely summarize the past progress and to present
      some future issues for the investigation into in vitro gamete production from
      pluripotent stem cells.

PMID- 17215489
TI  - Inflammation of choriodecidua induces tumor necrosis factor alpha-mediated
      apoptosis of human myometrial cells.
AB  - The present study investigated the ability of human choriodecidua to induce
      myometrial cell apoptosis through the secretion of tumor necrosis factor alpha
      (TNF). The secretion of TNF was evaluated in the culture supernatants of amnion
      and choriodecidua explants that were exposed to the bacterial endotoxin
      lipopolysaccharide (LPS) to mimic inflammation. The choriodecidua explants
      produced more TNF than the amnion explants in response to LPS stimulation,
      despite the fact that the choriodecidua had lower levels of TLR4 expression.
      Moreover, conditioned medium obtained from LPS-treated choriodecidua explants,
      but not that from amnion explants, decreased the number of viable cultured
      myometrial cells and induced cell apoptosis by inducing the overexpression of the
      proapoptotic protein BAX and by decreasing the expression of the anti-apoptotic
      protein BCL2. Neutralization of TNF in the choriodecidua-conditioned medium
      reversed this effect. Exogenous TNF mimicked LPS-treated choriodecidua
      conditioned medium in that it induced myometrial cell apoptosis, reduced BCL2
      expression, and increased BAX expression. Using neutralizing antibodies against
      both subtypes of TNF receptors, we found that only TNFRSF1A participates in TNF
      induced myometrial cell apoptosis. Our in vitro model of LPS-induced inflammation
      of human fetal membrane explants suggests a mechanism by which TNF secreted by
      choriodecidua governs human myometrial cell apoptosis at the end of pregnancy.
      These data support the hypothesis that TNF participates in the complex network of
      signaling processes associated with uterine involution.

PMID- 17215490
TI  - Interleukin 10 regulates inflammatory cytokine synthesis to protect against
      lipopolysaccharide-induced abortion and fetal growth restriction in mice.
AB  - Interleukin 10 (IL10) is a potent immune-regulating cytokine and inhibitor of
      inflammatory cytokine synthesis. To evaluate the anti-inflammatory role of IL10
      in pregnancy, the response of genetically IL10-deficient mice to low-dose
      lipopolysaccharide (LPS)-induced abortion was examined. When IL10-null mutant
      C57Bl/6 (Il10(-/-)) and control (Il10(+/+)) mice were administered low-dose LPS
      on Day 9.5 of gestation, IL10 deficiency predisposed to fetal loss accompanied by
      growth restriction in remaining viable fetuses, with an approximately 10-fold
      reduction in the threshold dose for 100% abortion. After LPS administration,
      inflammatory cytokines tumor necrosis factor-alpha (TNFA) and IL6 were markedly
      increased in serum, uterine, and conceptus tissues in Il10(-/-) mice compared
      with Il10(+/+) mice, with elevated local synthesis of Tnfa and Il6 mRNAs in the
      gestational tissues. IL1A and IL12p40 were similarly elevated in serum and
      gestational tissues, whereas interferon gamma (IFNG) and soluble TNFRII content
      were unchanged in the absence of IL10. Recombinant IL10 rescued the increased
      susceptibility to LPS-induced fetal loss in Il10(-/-) mice but did not improve
      outcomes in Il10(+/+) mice. IL10 genotype also influenced the responsiveness of
      mice to a TNFA antagonist, etanercept. Fetal loss in Il10(-/-) mice was partly
      alleviated by moderate or high doses of etanercept, whereas Il10(+/+) mice were
      refractory to high-dose etanercept, consistent with attenuation by IL10 status of
      TNFA bioavailability after etanercept treatment. These data show that IL10
      modulates resistance to inflammatory stimuli by downregulating expression of
      proinflammatory cytokines TNFA, IL6, IL1A, and IL12, acting to protect against
      inflammation-induced pathology in the implantation site.

PMID- 17215491
TI  - Expression of the cAMP-phosphodiesterase PDE4D isoforms and age-related changes
      in follicle-stimulating hormone-stimulated PDE4 activities in immature rat
      sertoli cells.
AB  - Major changes in the cAMP-dependent signal transduction pathway triggered by FSH
      take place during transition of rat Sertoli cells from proliferative to the
      quiescent/terminally differentiated state. Using Sertoli cell cultures isolated
      from 10-, 20-, and 30-day-old rats, we recorded a specific increase in PDE4
      activity in both the soluble and particulate subcellular fractions of 20-day-old
      Sertoli cells, which also displayed the highest cAMP response to FSH and the
      highest FSH-induced increase in PDE4 activity in both subcellular compartments.
      RT-PCR and immunoblotting experiments showed that almost all the PDE4D isoforms,
      known as the main cAMP-regulated rolipram-sensitive PDE in Sertoli cells, were
      expressed throughout the early postpartum period, whereas only the short PDE4D
      isoforms (PDE4D1 and PDE4D2) were transcriptionally regulated by FSH.
      Unexpectedly, the immunoblot data also revealed that the soluble PDE4 activities
      were mainly related to the long PDE4D isoforms and that short PDE4D1 was
      predominantly particulate. The subcellular distribution and expression of PDE4D
      proteins were unaffected by the developmental status of the Sertoli cells. Only
      the expression of short PDE4D1 appeared to be upregulated by FSH and only in 20
      day-old Sertoli cells, which suggests phenotype-dependent differential regulation
      of Pde4d1 mRNA translation. Resensitization of the cAMP response to FSH in 20-day
      old Sertoli cells was also associated with the highest FSH-induced transient
      increase in both soluble and particulate PDE4 activities, which suggests
      developmental changes in the PKA-mediated upregulation of the catalytic
      activities of long PDE4D. Such alterations may be involved in the phenotype
      dependent alterations in FSH receptor coupling with its associated G proteins in
      rat Sertoli cells.

PMID- 17215492
TI  - Evaluation of LRRK2 G2019S penetrance: relevance for genetic counseling in
      Parkinson disease.
AB  - We report the results of a family-based study of LRRK2 G2019S penetrance in
      Parkinson disease. We studied 19 families identified through the analysis of
      unrelated consecutive patients. The cumulative incidence of the disease was 15%
      at 60 years, 21% at 70 years, and 32% at 80 years. This study provides accurate
      estimates of G2019S penetrance by minimizing the selection bias.

PMID- 17215493
TI  - NF1 plexiform neurofibroma growth rate by volumetric MRI: relationship to age and
      body weight.
AB  - OBJECTIVE: To longitudinally analyze changes in plexiform neurofibroma (PN)
      volume in relation to age and body growth in children and young adults with
      neurofibromatosis type 1 and inoperable, symptomatic, or progressive PNs, using a
      sensitive, automated method of volumetric MRI analysis. METHODS: We included
      patients 25 years of age and younger with PNs entered in a natural history study
      or in treatment trials who had volumetric MRI over > or =16 months. RESULTS: We
      studied 49 patients (median age 8.3 years) with 61 PNs and a median evaluation
      period of 34 months (range 18 to 70). The PN growth rates varied among patients,
      but were constant within patients. Thirty-four patients (69%) experienced > or
      =20% increase in PN volume during the observation period. PN volume increased
      more rapidly than body weight over time (p = 0.026). Younger patients had the
      most rapid PN growth rate. CONCLUSIONS: Volume increase of plexiform
      neurofibromas is a realistic and meaningful trial endpoint. In most patients
      plexiform neurofibroma growth rate exceeded body growth rate. The youngest
      patients had the fastest plexiform neurofibroma growth rate, and clinical drug
      development should be directed toward this population. Age stratification for
      clinical trials for plexiform neurofibromas should be considered.

PMID- 17215494
TI  - Interhemispheric inhibition in distal and proximal arm representations in the
      primary motor cortex.
AB  - Interhemispheric inhibitory interactions (IHI) operate between homologous distal
      hand representations in primary motor cortex (M1). It is not known whether
      proximal arm representations exhibit comparable effects on their homologous
      counterparts. We studied IHI in different arm representations, targeting triceps
      brachii (TB, n = 13), first dorsal interosseous (FDI, n = 13), and biceps brachii
      (BB, n = 7) muscles in healthy volunteers. Transcranial magnetic stimulation test
      stimuli (TS) were delivered to M1 contralateral to the target muscle preceded 10
      ms by a conditioning stimulus (CS) to the opposite M1 at 110-150% resting motor
      threshold (RMT). IHI was calculated as the ratio between motor-evoked potential
      (MEP) amplitudes in conditioned relative to unconditioned trials. Mean RMTs were
      38.9, 46.9, and 46.0% of stimulator output in FDI, TB, and BB muscles,
      respectively. IHI was 0.45 +/- 0.41 (FDI), 0.78 +/- 0.38 (TB), and 0.52 +/- 0.32
      (BB, P < 0.01) when test MEP amplitudes were matched and 0.28 +/- 0.17 (FDI) and
      0.85 +/- 0.31 (TB, P < 0.05) when TS intensities expressed as percentage RMT were
      matched. Significant IHI (P < 0.05) was identified with minimal CS intensities
      (expressed as percentage stimulator output) in the 30 s for FDI, 60 s for TB, and
      40 s for BB. Additionally, a CS of roughly 120% RMT suppressed the test MEP but
      not a test H-reflex in BB, suggesting IHI observed in BB is likely mediated by a
      supraspinal mechanism. We conclude that IHI differs between different arm muscle
      representations, comparable between BB and FDI but lesser for TB. This finding
      suggests the amount of IHI between different arm representations does not
      strictly follow a proximal-to-distal gradient, but may be related to the role of
      each muscle in functional movement synergies.

PMID- 17215495
TI  - Novel role for reactive oxygen species as amplifiers of intermittent hypoxia.
      Focus on "Reactive oxygen species mediate central cardiorespiratory network
      responses to acute intermittent hypoxia".

PMID- 17215496
TI  - Should I stay or should I go? Neural substrates of being in the right place at
      the right time. Focus on "How prior reward experience biases exploratory
      movements: a probabilistic model".

PMID- 17215497
TI  - Evidence for Electrical Coupling in the SubCoeruleus (SubC) Nucleus.
AB  - SubCoeruleus (SubC) neurons, which are thought to modulate rapid-eye-movement
      (REM) sleep, were recorded in brain stem slices from 7- to 20-day rats and found
      to manifest spikelets, indicative of electrical coupling. Spikelets occurred
      spontaneously or could be induced by superfusion of the cholinergic agonist
      carbachol. Whole cell recordings revealed that carbachol induced membrane
      oscillations and spikelets in the theta frequency range in SubC neurons in the
      presence of fast synaptic blockers. Electrical coupling in neurons is mediated by
      the gap junction protein connexin 36 (Cx 36). We found that Cx 36 gene expression
      and protein in the mesopontine tegmentum decreased during development. Cx 36
      protein levels specifically in the SubC decreased in concert with the
      developmental decrease in REM sleep. The presence of electrical coupling in the
      SubC introduces a novel potential mechanism of action for the regulation of sleep
      wake states.

PMID- 17215498
TI  - Responses of the rat olfactory epithelium to retronasal air flow.
AB  - Responses of the rat olfactory epithelium were assessed with the
      electroolfactogram while odorants were presented to the external nares with an
      artificial sniff or to the internal nares by positive pressure. A series of seven
      odorants that varied from very polar, hydrophilic odorants to very nonpolar,
      hydrophobic odorants were used. Although the polar odorants activated the dorsal
      olfactory epithelium when presented by the external nares (orthonasal
      presentation), they were not effective when forced through the nasal cavity from
      the internal nares (retronasal presentation). However, the nonpolar odorants were
      effective in both stimulus modes. These results were independent of stimulus
      concentration or of humidity of the carrier air. Similar results were obtained
      with multiunit recordings from olfactory bulb. These results help to explain why
      human investigations often report differences in the sensation or ability to
      discriminate odorants presented orthonasally versus retronasally. The results
      also strongly support the importance of odorant sorption in normal olfactory
      processes.

PMID- 17215499
TI  - Is there a common origin to surround-inhibition as seen through electrical
      activity versus hemodynamic changes? Focus on "Duration-dependent response in SI
      to vibrotactile stimulation in squirrel monkey".

PMID- 17215500
TI  - Group I metabotropic glutamate receptors are differentially expressed by two
      populations of olfactory bulb granule cells.
AB  - In the main olfactory bulb, several populations of granule cells (GCs) can be
      distinguished based on the soma location either superficially, interspersed with
      mitral cells within the mitral cell layer (MCL), or deeper, within the GC layer
      (GCL). Little is known about the physiological properties of superficial GCs
      (sGCs) versus deep GCs (dGCs). Here, we used patch-clamp recording methods to
      explore the role of Group I metabotropic glutamate receptors (mGluRs) in
      regulating the activity of GCs in slices from wildtype and mGluR-/- mutant mice.
      In wildtype mice, bath application of the selective Group I mGluR agonist DHPG
      depolarized and increased the firing rate of both GC subtypes. In the presence of
      blockers of fast synaptic transmission (APV, CNQX, gabazine), DHPG directly
      depolarized both GC subtypes, although the two GC subtypes responded
      differentially to DHPG in mGluR1-/- and mGluR5-/- mice. DHPG depolarized sGCs in
      slices from mGluR5-/- mice, although it had no effect on sGCs in slices from
      mGluR1-/- mice. By contrast, DHPG depolarized dGCs in slices from mGluR1-/- mice
      but had no effect on dGCs in slices from mGluR5-/- mice. Previous studies showed
      that mitral cells express mGluR1 but not mGluR5. The present results therefore
      suggest that sGCs are more similar to mitral cells than dGCs in terms of mGluR
      expression.

PMID- 17215501
TI  - Lesions of area 5 of the posterior parietal cortex in the cat produce errors in
      the accuracy of paw placement during visually guided locomotion.
AB  - We developed a novel locomotor task in which cats step over obstacles that move
      at a different speed from that of the treadmill on which the cat is walking: we
      refer to this as a visual dissociation locomotion task. Slowing the speed of the
      obstacle with respect to that of the treadmill sometimes led to a major change in
      strategy so that cats made two steps with the hindlimbs before stepping over the
      obstacle (double step strategy) instead of the single step (standard strategy)
      observed when the obstacle was at the same speed as the treadmill. In addition,
      in the step preceding the step over the obstacle, the paws were placed
      significantly closer to the obstacle in the visual dissociation task than when
      the treadmill and the obstacle were at the same speed. After unilateral lesion of
      area 5 of the posterior parietal cortex (PPC), the cats frequently hit the
      obstacle as they stepped over it, especially in the visual dissociation task.
      This locomotor deficit was linked to significant differences in the location in
      which the forelimbs were placed in the step preceding that over the obstacle
      compared with the prelesion control. Cats also frequently hit the obstacle with
      their hindlimbs even when the forelimbs negotiated the obstacle successfully;
      this suggests an important role for the posterior parietal cortex in the
      coordination of the forelimbs and hindlimbs. Together, these results suggest an
      important contribution of the PPC to the planning of visually guided gait
      modifications.

PMID- 17215502
TI  - Effects of mu-opioid receptor modulation on GABAB receptor synaptic function in
      hippocampal CA1.
AB  - Activation of mu-opioid receptors (MORs) alters information coding, synaptic
      plasticity, and spatial memory in hippocampal CA1. In CA1, MORs act by inhibiting
      GABA release onto both GABA(A) and GABA(B) receptors exclusively. MOR activation
      can facilitate excitatory inputs in CA1 dendritic layers by inhibiting synaptic
      activation of GABA(A) receptors. In this study, we use voltage-sensitive dye
      imaging to show that MOR activation by the MOR agonist DAMGO suppressed GABA(B)
      inhibitory postsynaptic potentials in all layers of CA1. When stimulating
      excitatory input in stratum oriens (SO), stratum radiatum (SR), or stratum
      lacunosum-moleculare (SLM) with five pulses at 20 Hz in the presence of
      bicuculline (50 microM), DAMGO (1 muM) was most effective at increasing the
      amplitude of the last excitatory event. This effect was reversed by the MOR
      antagonist CTOP (1 muM) and occluded by the GABA(B) receptor agonist CGP 55845
      (10 microM). DAMGO was less effective at increasing the amplitude of later
      excitatory events compared with the effect of CGP 55845. DAMGO was relatively
      ineffective at increasing the amplitude of excitatory inputs in SLM but had
      significantly greater effects on excitatory events as they propagated to stratum
      pyramidale (SP). When stimulating in SR, DAMGO was least effective at increasing
      excitatory amplitudes in SLM and most effective in SP and SO. Finally, DAMGO was
      equally effective at increasing excitatory activity amplitudes in all layers of
      CA1 after stimulating in SO. Therefore MOR suppresses GABA(B) synaptic
      hyperpolarizations in all layers of CA1 and most effectively facilitates
      excitatory activity in CA1 output layers.

PMID- 17215503
TI  - Psychophysical evidence for long-term potentiation of C-fiber and Adelta-fiber
      pathways in humans by analysis of pain descriptors.
AB  - Long-term potentiation of human pain perception (nociceptive LTP) to single
      electrical test stimuli was induced by high-frequency stimulation (HFS) of
      cutaneous nociceptive afferents. Numerical pain ratings and a list of sensory
      pain descriptors disclosed the same magnitude of nociceptive LTP (23% increase
      for >60 min, P < 0.001), whereas affective pain descriptors were not
      significantly enhanced. Factor analysis of the sensory pain descriptors showed
      that facilitation was restricted to two factors characterized by hot and burning
      (+41%) and piercing and stinging (+21%, both P < 0.01), whereas a factor
      represented by throbbing and beating was not significantly increased (+9%, P =
      0.47). The increased perception of the burning pain quality for >1 h after HFS is
      interpreted as a LTP-like facilitation of the conditioned cutaneous C-fiber
      pathway. Additionally, the increase of the stinging pain quality supplied
      evidence for facilitation of a sharpness-sensitive Adelta-fiber pathway.

PMID- 17215504
TI  - Dissociated representations of irritation and valence in human primary olfactory
      cortex.
AB  - Irritation and negative valence are closely associated in perception. However,
      these perceptual aspects can be dissociated in olfaction where irritation can
      accompany both pleasant and unpleasant odorants. Whereas the sensation of odor
      reflects transduction at olfactory receptors, irritation reflects concurrent
      transduction of the odorant at trigeminal receptors. Thus a stimulus can be
      either a pure olfactant activating the olfactory receptors only or a bimodal
      odorant activating both types of receptors. Using event-related functional
      magnetic resonance imaging and a 2 x 2 experimental design contrasting odorant
      valence (pleasant/unpleasant) and odorant type (pure olfactant/bimodal) we found
      activity in piriform cortex to be associated with valence, and not type, of
      odors. In contrast, activity in the olfactory tubercle was associated with type,
      and not valence, of odors. Importantly, this was found when perceived intensity
      was held equal across odorants. These findings suggest that dissociable neural
      substrates subserve the encoding of irritation and valence in olfaction.

PMID- 17215505
TI  - Synapses in the fly motion-vision pathway: evidence for a broad range of signal
      amplitudes and dynamics.
AB  - Synapses are generally considered to operate efficiently only when their
      signaling range matches the spectrum of prevailing presynaptic signals in terms
      of both amplitudes and dynamics. However, the prerequisites for optimally
      matching the signaling ranges may differ between spike-mediated and graded
      synaptic transmission. This poses a problem for synapses that convey both graded
      and spike signals at the same time. We addressed this issue by tracing
      transmission systematically in vivo in the blowfly's visual-motion pathway by
      recording from single neurons that receive mixed potential signals consisting of
      rather slow graded fluctuations superimposed with highly variable spikes from a
      small number of presynaptic elements. Both pre- and postsynaptic neurons were
      previously shown to represent preferred-direction motion velocity reliably and
      linearly at low fluctuation frequencies. To selectively assess the performance of
      individual synapses and to precisely control presynaptic signals, we voltage
      clamped one of the presynaptic neurons. Results showed that synapses can
      effectively convey signals over a much larger amplitude and frequency range than
      is normally used during graded transmission of visual signals. An explanation for
      this unexpected finding might lie in the transmission of the spike component that
      reaches larger amplitudes and contains higher frequencies than graded signals.

PMID- 17215506
TI  - Functional imaging reveals respiratory network activity during hypoxic and opioid
      challenge in the neonate rat tilted sagittal slab preparation.
AB  - In mammals, respiration-modulated networks are distributed rostrocaudally in the
      ventrolateral quadrant of the medulla. Recent studies have established that in
      neonate rodents, two spatially separate networks along this column-the parafacial
      respiratory group (pFRG) and the pre-Botzinger complex (preBotC)-are hypothesized
      to be sufficient for respiratory rhythm generation, but little is known about the
      connectivity within or between these networks. To be able to observe how these
      networks interact, we have developed a neonate rat medullary tilted sagittal
      slab, which exposes one column of respiration-modulated neurons on its surface,
      permitting functional imaging with cellular resolution. Here we examined how
      respiratory networks responded to hypoxic challenge and opioid-induced
      depression. At the systems level, the sagittal slab was congruent with more
      intact preparations: hypoxic challenge led to a significant increase in
      respiratory period and inspiratory burst amplitude, consistent with gasping. At
      opioid concentrations sufficient to slow respiration, we observed periods at
      integer multiples of control, matching quantal slowing. Consistent with single
      unit recordings in more intact preparations, respiratory networks were
      distributed bimodally along the rostrocaudal axis, with respiratory neurons
      concentrated at the caudal pole of the facial nucleus, and 350 microns caudally,
      at the level of the pFRG and the preBotC, respectively. Within these regions
      neurons active during hypoxia- and/or opioid-induced depression were ubiquitous
      and interdigitated. In particular, contrary to earlier reports, opiate
      insensitive neurons were found at the level of the preBotC.

PMID- 17215507
TI  - Functional roles of Kv1 channels in neocortical pyramidal neurons.
AB  - Pyramidal neurons from layers II/III of somatosensory and motor cortex express
      multiple Kv1 alpha-subunits and a current sensitive to block by alpha-dendrotoxin
      (alpha-DTX). We examined functional roles of native Kv1 channels in these cells
      using current-clamp recordings in brain slices and current- and voltage-clamp
      recordings in dissociated cells. alpha-DTX caused a significant negative shift in
      voltage threshold for action potentials (APs) and reduced rheobase.
      Correspondingly, a ramp-voltage protocol revealed that the alpha-DTX-sensitive
      current activated at subthreshold voltages. AP width at threshold increased with
      successive APs during repetitive firing. The steady-state threshold width for a
      given firing rate was similar in control and alpha-DTX, despite an initially
      broader AP in alpha-DTX. AP voltage threshold increased similarly during a train
      of spikes under control conditions and in the presence of alpha-DTX. alpha-DTX
      had no effect on input resistance or resting membrane potential and modest
      effects on the amplitude or width of a single AP. Accordingly, experiments using
      AP waveforms (APWs) as voltage protocols revealed that alpha-DTX-sensitive
      current peaked late during the AP repolarization phase. Application of alpha-DTX
      increased the rate of firing to intracellular current injection and increased
      gain (multiplicative effects), but did not alter spike-frequency adaptation.
      Consistent with these findings, voltage-clamp experiments revealed that the
      proportion of outward current sensitive to alpha-DTX was highest during the
      interval between two APWs, reflecting slow deactivation kinetics at -50 mV.
      Finally, alpha-DTX did not alter the selectivity of pyramidal neurons for DC
      versus time-varying stimuli.

PMID- 17215508
TI  - Postural context alters the stability of bimanual coordination by modulating the
      crossed excitability of corticospinal pathways.
AB  - The tendency for movements of the upper limbs to be drawn systematically toward
      one another and to follow similar spatiotemporal trajectories is well known.
      Although suppression of this tendency is integral to tasks of daily living, its
      exploitation may prove to be critical in the rehabilitation of acquired
      hemiplegias. In general, however, the task-related factors that determine the
      degree of coupling between the upper limbs and the mechanisms that mediate
      bilateral interactions between neural pathways projecting to the muscles of the
      arm and hand are not yet well understood. We present evidence that the postural
      context in which human participants perform upper limb movements determines the
      relative stability of patterns of bimanual coordination. Manipulation of the axes
      of rotation of forearm movements reversed the relative stability of simultaneous
      and alternating patterns of bimanual coordination. Transcranial magnetic
      stimulation of motor cortex revealed that these manipulations of postural context
      altered the crossed modulation of excitability in corticospinal pathways that
      arises from movement of the opposite limb. Furthermore, modulation of responses
      to electrical stimulation of the cervicomedullary junction indicated that crossed
      modulation was also expressed at the level of the spinal motoneurons. Our data
      support the view that crossed modulation of excitability in corticospinal
      pathways mediates the stability of bimanual coordination. Furthermore, task
      related factors that are sufficient to give rise to changes in the stability of
      bimanual coordination are accompanied by crossed modulation of excitability at
      multiple levels of the neuraxis, indicative of a failure of inhibitory control.

PMID- 17215509
TI  - Characteristics and mechanisms of locomotion induced by intraspinal
      microstimulation and dorsal root stimulation in spinal cats.
AB  - Intraspinal microstimulation (ISMS) through a single microelectrode can induce
      locomotion in cats spinalized at T(13) 1 wk before (untrained) or after 3-5 wk of
      treadmill training. Here we study the optimal parameters of ISMS and the
      characteristics of locomotion evoked. ISMS was applied in the dorsal region of
      segments L(3)-S(1) at different lateralities (midline to 2.5 mm) and after an
      intravenous injection of clonidine (noradrenergic agonist). Kinematics and
      electromyographic recordings were used to characterize locomotion. ISMS could
      induce a bilateral locomotor pattern similar to that obtained with perineal
      stimulation, and the characteristics of locomotion varied according to the spinal
      segment stimulated. Mechanisms by which ISMS could evoke locomotion were then
      investigated by stimulating, inactivating, or lesioning different spinal
      structures. Dorsal root stimulation (DRS), just like ISMS, could evoke a variety
      of ipsi- and bilateral nonlocomotor movements as well as locomotor responses.
      This suggests that sensory afferent pathways are involved in the production of
      locomotion by ISMS. Microinjections of yohimbine (noradrenergic antagonist) in
      L(3) and L(4) segments or a complete second spinal lesion at L(3)-L(4) abolished
      all locomotor activity evoked by ISMS applied at more caudal segments.
      Progressive dorsoventral spinal lesions at L(3) or L(4) and restricted ventral
      lesions at L(4) further suggest that the integrity of the ventral or
      ventrolateral funiculi as well as the L(3)-L(4) segments are critical for the
      induction of locomotion by ISMS at L(5) to S(1) or by DRS at these caudal
      segments.

PMID- 17215510
TI  - Intraspinal stimulation caudal to spinal cord transections in rats. Testing the
      propriospinal hypothesis.
AB  - Many laboratories have reported the successful regeneration of neurons across
      damaged portions of the spinal cord. Associated improvements in hindlimb
      locomotor movements have been attributed to the formation of functional neuronal
      connections with the locomotor central pattern generator (CPG). However,
      regenerating axons generally extend no more than 10 mm caudal to the lesion
      sites, terminating about 20 mm short of the lumbar segments thought to contain
      the CPG. It has therefore tacitly been assumed that the locomotor improvements
      arose from activation of propriospinal neurons relaying excitation to the CPG.
      Here we report a test of this assumption, which we call the propriospinal
      hypothesis. Intraspinal microstimulation (ISMS) was used to activate the putative
      propriospinal relay neurons. Approximately 2-3 wk after complete spinal cord
      transection at T8-T9 in rats, an array of six Pt-Ir microwires was chronically
      implanted in the intermediate and ventral gray matter of T10-T12 segments. ISMS
      pulse trains with amplitudes of 0.8-0.9 times threshold for activating axial
      muscles were delivered during open-field locomotor tests (BBB). ISMS
      significantly increased BBB scores over control tests, but did not produce limb
      coordination and weight bearing sufficient for locomotion. These results support
      the main assumption of the propriospinal hypothesis: that neuronal activity
      elicited in thoracic spinal segments caudal to a complete spinal cord transection
      may propagate caudally and activate the locomotor CPG.

PMID- 17215511
TI  - Modulation of extrasynaptic THIP conductances by GABAA-receptor modulators in
      mouse neocortex.
AB  - THIP is a hypnotic drug, which displays a unique pharmacological profile, because
      it activates a subset of extrasynaptic gamma-aminobutyric acid type A (GABA(A))
      receptors containing delta-subunits. It is important to study the physiology and
      pharmacology of these extrasynaptic receptors and to determine how THIP interacts
      with other hypnotics and anesthetics. Here, we study the modulation of the
      extrasynaptic response to THIP using three classes of GABA(A)-receptor ligands.
      In whole cell recordings from mouse neocortical layer 2/3 pyramidal cells, THIP
      induced an extrasynaptic tonic current of 44 +/- 5 pA. The benzodiazepine site
      agonist and hypnotic zolpidem (500 nM), which displays selectivity for
      alpha(1/2/3)- and gamma(2)-containing receptors, did not alter the tonic current
      induced by THIP. The anesthetic etomidate (1 microM), which shows selectivity for
      beta(2)- and beta(3)-containing GABA(A) receptors, potentiated the THIP current
      by 126%. Etomidate also induced a small tonic GABA(A) current per se. The
      anesthetic propofol (1 microM), which displays broad-spectrum modulatory effects
      on several GABA(A)-receptor subtypes, enhanced the tonic THIP current by 117%.
      Finally, all three compounds modulated the function of intrasynaptic receptors
      activated by synaptically released GABA. Our study shows that the extrasynaptic
      GABA(A) receptors responsible for the tonic THIP conductance likely do not
      contain alpha(1)-, alpha(2)-, alpha(3)-, and gamma(2)-subunits. Thus the tonic
      GABAergic conductance in the neocortex is presumably mediated by
      alpha(4)beta(2/3)delta receptors, which are likely to play a major role for
      neocortical excitability. Furthermore, our study has deepened the knowledge about
      the cellular actions of THIP as well as THIP's interactions with other hypnotics
      and anesthetics.

PMID- 17215512
TI  - Internal pallidal neuronal activity during mild drug-related dyskinesias in
      Parkinson's disease: decreased firing rates and altered firing patterns.
AB  - The neuronal basis of hyperkinetic movement disorders has long been unclear. We
      now test the hypothesis that changes in the firing pattern of neurons in the
      globus pallidus internus (GPi) are related to dyskinesias induced by low doses of
      apomorphine in patients with advanced Parkinson's disease (PD). During
      pallidotomy for advanced PD, the activity of single neurons was studied both
      before and after administration of apomorphine at doses just adequate to induce
      dyskinesias (21 neurons, 17 patients). After the apomorphine injection, these
      spike trains demonstrated an initial fall in firing from baseline. In nine
      neurons, the onset of on was simultaneous with that of dyskinesias. In these
      spike trains, the initial fall in firing rate preceded and was larger than the
      fall at the onset of on with dyskinesias. Among the three neurons in which the
      onset of on occurred before that of dyskinesias, the firing rate did not change
      at the time of onset of dyskinesias. After injection of apomorphine, dyskinesias
      during on with dyskinesias often fluctuated between transient periods with
      dyskinesias and those without. Average firing rates were not different between
      these two types of transient periods. Transient periods with dyskinesias were
      characterized by interspike interval (ISI) independence, stationary spike trains,
      and higher variability of ISIs. A small but significant group of neurons
      demonstrated recurring ISI patterns during transient periods of on with
      dyskinesias. These results suggest that mild dyskinesias resulting from low doses
      of apomorphine are related to both low GPi neuronal firing rates and altered
      firing patterns.

PMID- 17215513
TI  - Aurora-B regulates RNA methyltransferase NSUN2.
AB  - Disassembly of the nucleolus during mitosis is driven by phosphorylation of
      nucleolar proteins. RNA processing stops until completion of nucleolar
      reformation in G(1) phase. Here, we describe the RNA methyltransferase NSUN2, a
      novel substrate of Aurora-B that contains an NOL1/NOP2/sun domain. NSUN2 was
      concentrated in the nucleolus during interphase and was distributed in the
      perichromosome and cytoplasm during mitosis. Aurora-B phosphorylated NSUN2 at
      Ser139. Nucleolar proteins NPM1/nucleophosmin/B23 and nucleolin/C23 were
      associated with NSUN2 during interphase. In mitotic cells, association between
      NPM1 and NSUN2 was inhibited, but NSUN2-S139A was constitutively associated with
      NPM1. The Aurora inhibitor Hesperadin induced association of NSUN2 with NPM1 even
      in mitosis, despite the silver staining nucleolar organizer region disassembly.
      In vitro methylation experiments revealed that the Aurora-B-phosphorylation and
      the phosphorylation-mimic mutation (S139E) suppressed methyltransferase
      activities of NSUN2. These results indicate that Aurora-B participates to
      regulate the assembly of nucleolar RNA-processing machinery and the RNA
      methyltransferase activity of NSUN2 via phosphorylation at Ser139 during mitosis.

PMID- 17215514
TI  - VAMP8/endobrevin as a general vesicular SNARE for regulated exocytosis of the
      exocrine system.
AB  - The molecular mechanism governing the regulated secretion of most exocrine
      tissues remains elusive, although VAMP8/endobrevin has recently been shown to be
      the major vesicular SNARE (v-SNARE) of zymogen granules of pancreatic exocrine
      acinar cells. In this article, we have characterized the role of VAMP8 in the
      entire exocrine system. Immunohistochemical studies showed that VAMP8 is
      expressed in all examined exocrine tissues such as salivary glands, lacrimal
      (tear) glands, sweat glands, sebaceous glands, mammary glands, and the prostate.
      Severe anomalies were observed in the salivary and lacrimal glands of VAMP8-null
      mice. Mutant salivary glands accumulated amylase and carbonic anhydrase VI.
      Electron microscopy revealed an accumulation of secretory granules in the acinar
      cells of mutant parotid and lacrimal glands. Pilocarpine-stimulated secretion of
      saliva proteins was compromised in the absence of VAMP8. Protein aggregates were
      observed in mutant lacrimal glands. VAMP8 may interact with syntaxin 4 and SNAP
      23. These results suggest that VAMP8 may act as a v-SNARE for regulated secretion
      of the entire exocrine system.

PMID- 17215515
TI  - Increased common fragile site expression, cell proliferation defects, and
      apoptosis following conditional inactivation of mouse Hus1 in primary cultured
      cells.
AB  - Targeted disruption of the mouse Hus1 cell cycle checkpoint gene results in
      embryonic lethality and proliferative arrest in cultured cells. To investigate
      the essential functions of Hus1, we developed a system for the regulated
      inactivation of mouse Hus1 in primary fibroblasts. Inactivation of a loxP site
      flanked conditional Hus1 allele by using a cre-expressing adenovirus resulted in
      reduced cell doubling, cell cycle alterations, and increased apoptosis. These
      phenotypes were associated with a significantly increased frequency of gross
      chromosomal abnormalities and an S-phase-specific accumulation of phosphorylated
      histone H2AX, an indicator of double-stranded DNA breaks. To determine whether
      these chromosomal abnormalities occurred randomly or at specific genomic regions,
      we assessed the stability of common fragile sites, chromosomal loci that are
      prone to breakage in cells undergoing replication stress. Hus1 was found to be
      essential for fragile site stability, because spontaneous chromosomal
      abnormalities occurred preferentially at common fragile sites upon conditional
      Hus1 inactivation. Although p53 levels increased after Hus1 loss, deletion of p53
      failed to rescue the cell-doubling defect or increased apoptosis in conditional
      Hus1 knockout cells. In summary, we propose that Hus1 loss leads to chromosomal
      instability during DNA replication, triggering increased apoptosis and impaired
      proliferation through p53-independent mechanisms.

PMID- 17215516
TI  - The anaphase-promoting complex coordinates initiation of lens differentiation.
AB  - Lens development requires the precise coordination of cell division and
      differentiation. The mechanisms by which the differentiation program is initiated
      after cell cycle arrest remains not well understood. Cyclin-dependent kinase
      inhibitors (CKIs), such as p15 and p21, have been suggested to be critical
      components that inhibit G1 progression and therefore, their activation is
      necessary for quiescence and important for the onset of differentiation.
      Regulation of p15 and p21 is principally governed by transforming growth factor
      (TGF)-beta-signaling pathway. We have identified that Cdh1/APC, a critical
      ubiquitin protein ligase, plays an important role in regulating lens
      differentiation by facilitating TGF-beta-induced degradation of SnoN, a
      transcriptional corepressor that needs to be removed for transcriptional
      activation of p15 and p21. The depletion of Cdh1 by RNA interference attenuates
      the TGF-beta-mediated induction of p15 and p21 and significantly blocks lens
      differentiation. Expression of nondegradable SnoN also noticeably attenuates lens
      induction. Furthermore, we have shown that Cdh1 and SnoN form a complex at the
      onset of lens differentiation. In vivo histological analysis confirms our
      biochemical and genetic results. Thus, Cdh1/APC is crucial to the coordination of
      cell cycle progression and the initiation of lens differentiation through
      mediating TGF-beta-signaling-induced destruction of SnoN.

PMID- 17215517
TI  - Role of the Sec61 translocon in EGF receptor trafficking to the nucleus and gene
      expression.
AB  - The epidermal growth factor (EGF)-dependent trafficking of the intact EGF
      receptor to the nucleus and its requirement for growth factor induction of cyclin
      D and other genes has been reported. Unresolved is the mechanism by which this or
      other transmembrane proteins are excised from a lipid bilayer before nuclear
      translocalization. We report that, after the addition of EGF, the cell surface
      EGF receptor is trafficked to the endoplasmic reticulum (ER) where it associates
      with Sec61beta, a component of the Sec61 translocon, and is retrotranslocated
      from the ER to the cytoplasm. Abrogation of Sec61beta expression prevents EGF
      dependent localization of EGF receptors to the nucleus and expression of cyclin
      D. This indicates that EGF receptors are trafficked from the ER to the nucleus by
      a novel pathway that involves the Sec61 translocon.

PMID- 17215518
TI  - PP2B-mediated dephosphorylation of c-Jun C terminus regulates phorbol ester
      induced c-Jun/Sp1 interaction in A431 cells.
AB  - The c-Jun/Sp1 interaction is essential for growth factor- and phorbol 12
      myristate 13-acetate (PMA)-induced genes expression, including human 12(S)
      lipoxygenase, keratin 16, cytosolic phospholipase A2, p21(WAF1/CIP1), and
      neuronal nicotinic acetylcholine receptor beta4. Here, we examined the mechanism
      underlying the PMA-induced regulation on the interaction between c-Jun and Sp1.
      We found that treatment of cells with PMA induced a dephosphorylation at the C
      terminus of c-Jun at Ser-243 and a concomitant inhibition of PP2B by using PP2B
      small interfering RNA, resulting in reduction of PMA-induced gene expression as
      well as the c-Jun/Sp1 interaction. The c-Jun mutant TAM-67-3A, which contains
      three substitute alanines at Thr-231, Ser-243, and Ser-249 compared with TAM-67,
      binds more efficaciously with Sp1 and is about twice as efficacious as TAM-67 in
      inhibiting the PMA-induced activation of the 12(S)-lipoxygenase promoter.
      Importantly, PP2B not only dephosphorylates the c-Jun at Ser-243 but also
      interacts with c-Jun in PMA-treated cells. PMA stimulates the association of the
      PP2B/c-Jun/Sp1 complex with the promoter. These findings indicate the
      dephosphorylation of c-Jun C terminus is required for the c-Jun/Sp1 interaction
      and reveal that PP2B plays an important role in regulating c-Jun/Sp1 interaction
      in PMA-induced gene expression.

PMID- 17215519
TI  - Cell contact-dependent regulation of epithelial-myofibroblast transition via the
      rho-rho kinase-phospho-myosin pathway.
AB  - Epithelial-mesenchymal-myofibroblast transition (EMT), a key feature in organ
      fibrosis, is regulated by the state of intercellular contacts. Our recent studies
      have shown that an initial injury of cell-cell junctions is a prerequisite for
      transforming growth factor-beta1 (TGF-beta1)-induced transdifferentiation of
      kidney tubular cells into alpha-smooth muscle actin (SMA)-expressing
      myofibroblasts. Here we analyzed the underlying contact-dependent mechanisms.
      Ca(2+) removal-induced disruption of intercellular junctions provoked Rho/Rho
      kinase (ROK)-mediated myosin light chain (MLC) phosphorylation and Rho/ROK
      dependent SMA promoter activation. Importantly, myosin-based contractility itself
      played a causal role, because the myosin ATPase inhibitor blebbistatin or a
      nonphosphorylatable, dominant negative MLC (DN-MLC) abolished the contact
      disruption-triggered SMA promoter activation, eliminated the synergy between
      contact injury and TGF-beta1, and suppressed SMA expression. To explore the
      responsible mechanisms, we investigated the localization of the main SMA-inducing
      transcription factors, serum response factor (SRF), and its coactivator myocardin
      related transcription factor (MRTF). Contact injury enhanced nuclear accumulation
      of SRF and MRTF. These processes were inhibited by DN-Rho or DN-MLC. TGF-beta1
      strongly facilitated nuclear accumulation of MRTF in cells with reduced contacts
      but not in intact epithelia. DN-myocardin abrogated the Ca(2+)-removal- +/- TGF
      beta1-induced promoter activation. These studies define a new mechanism whereby
      cell contacts regulate epithelial-myofibroblast transition via Rho-ROK-phospho
      MLC-dependent nuclear accumulation of MRTF.

PMID- 17215520
TI  - Endoplasmic reticulum and Golgi localization sequences for mammalian target of
      rapamycin.
AB  - Mammalian target of rapamycin (mTOR) forms two complexes, mTORC1 and mTORC2, that
      play central roles in cell growth and functions. Only mTORC1 is directly
      inhibited by the immunosuppressive drug rapamycin. Despite recent progress in
      identifying new components and functions of the mTOR pathway, relatively little
      is known about the spatial arrangement of mTOR signaling and the underlying
      mechanisms. In a previous study, we showed that a large proportion of mTOR is
      localized to the endoplasmic reticulum (ER) and Golgi in many common cell lines.
      Here, we report the identification of an internal mTOR sequence that contains two
      HEAT (HT) repeats, HT18 and HT19, and two intervening interunit spacers (IUSs),
      IUS17 and IUS18, which is sufficient to target enhanced green fluorescent protein
      to the Golgi. Surprisingly, deletion of IUS17 from this Golgi localization
      sequence (GLS) converts it to an ER localization sequence (ELS). Deletion of
      HT19, a common element of both GLS and ELS from the full-length mTOR, causes
      delocalization of mTOR and inhibits the ability of mTOR to promote S6
      phosphorylation. Moreover, overexpression of GLS and ELS inhibits both mTOR
      complexes. Together, our results reveal unusual ER- and Golgi-targeting sequences
      and suggest that anchoring to these organelles is important for the functions of
      mTOR complexes.

PMID- 17215522
TI  - Angiopoietin chemotactic activities on neutrophils are regulated by PI-3K
      activation.
AB  - Angiopoietins (Ang1 and Ang2) modulate blood vessel integrity during the
      angiogenic process through the activation of tyrosine kinase receptor (Tie2). We
      recently detected Tie2 expression on neutrophils and reported that angiopoietins
      induce acute proinflammatory events including neutrophil beta2-integrin
      activation and their adhesion onto endothelial cells. Herein, we investigated the
      effect of angiopoietins on neutrophil migration and their capacity to modulate
      CXCL8/IL-8 chemotactic properties. Using a Boyden chamber assay, we observed that
      Ang1 and Ang2 (up to 10 nM; 60 min) increased the migration of neutrophils, and
      the maximal effect was achieved at 1 nM (72% and 114% increase, respectively) as
      compared with untreated cells. Angiopoietins induce a rapid and transient Akt
      phosphorylation, and pretreatment of neutrophils with PI-3K inhibitors,
      wortmannin (100 nM) and LY294002 (500 nM), reduced Ang1-mediated neutrophil
      migration by 100% and 78% and Ang2 chemotactic activity by 100% and 71%,
      respectively. Treatment of neutrophils with CXCL8/IL-8 (up to 50 nM; 60 min)
      increased basal neutrophil migration by 257% at its optimal concentration (10
      nM), and pretreatment of neutrophils with corresponding PI-3K inhibitors reduced
      CXCL8/IL-8 (1 nM) chemotactic effect. Pretreatment of neutrophils with Ang1 or
      Ang2 (10 nM; 15 min) potentiated neutrophil migration induced by CXCL8/IL-8 (1 or
      10 nM; 60 min) by 263% and 238% and by 177% and 164%, respectively. Finally, both
      angiopoietins showed a synergistic effect on the induction of Akt phosphorylation
      mediated by CXCL8/IL-8. In summary, our data demonstrate that angiopoietins
      increase neutrophil migration through PI-3K activation and can enhance
      proinflammatory activities of other cytokines.

PMID- 17215521
TI  - EphA4 signaling regulates blastomere adhesion in the Xenopus embryo by recruiting
      Pak1 to suppress Cdc42 function.
AB  - The control of cell adhesion is an important mechanism by which Eph receptors
      regulate cell sorting during development. Activation of EphA4 in Xenopus
      blastulae induces a reversible, cell autonomous loss-of-adhesion and disruption
      of the blastocoel roof. We show this phenotype is rescued by Nckbeta (Grb4)
      dependent on its interaction with EphA4. Xenopus p21(Cdc42/Rac)-activated kinase
      xPAK1 interacts with Nck, is activated in embryo by EphA4 in an Nck-dependent
      manner, and is required for EphA4-induced loss-of-adhesion. Ectopic expression of
      xPAK1 phenocopies EphA4 activation. This does not require the catalytic activity
      of xPAK1, but it does require its GTPase binding domain and is enhanced by
      membrane targeting. Indeed, membrane targeting of the GTPase binding domain (GBD)
      of xPAK1 alone is sufficient to phenocopy EphA4 loss-of-adhesion. Both EphA4 and
      the xPAK1-GBD down-regulate RhoA-GTP levels, and consistent with this, loss-of
      adhesion can be rescued by activated Cdc42, Rac, and RhoA and can be
      epistatically induced by dominant-negative RhoA. Despite this, neither Cdc42 nor
      Rac activities are down-regulated by EphA4 activation or by the xPAK1-GBD.
      Together, the data suggest that EphA4 activation sequesters active Cdc42 and in
      this way down-regulates cell-cell adhesion. This novel signaling pathway suggests
      a mechanism for EphA4-guided migration.

PMID- 17215523
TI  - Pivotal advance: CTLA-4+ T cells exhibit normal antiviral functions during acute
      viral infection.
AB  - Previous studies have shown that T cells, which are genetically deficient in CTLA
      4/CD152 expression, will proliferate uncontrollably, resulting in lethal
      autoimmune disease. This and other evidence indicate that CTLA-4 plays a critical
      role in the negative regulation of effector T cell function. In contrast to
      expectations, BrdU incorporation experiments demonstrated that CTLA-4 expression
      was associated with normal or even enhanced in vivo proliferation of virus
      specific CD4+ and CD8+ T cells following acute lymphocytic choriomeningitis virus
      or vaccinia virus infection. When compared with CTLA-4- T cells directly ex vivo,
      CTLA-4+ T cells also exhibited normal antiviral effector functions following
      stimulation with peptide-coated cells, virus-infected cells, plate-bound anti
      CD3/anti-CTLA-4, or the cytokines IL-12 and IL-18. Together, this indicates that
      CTLA-4 does not directly inhibit antiviral T cell expansion or T cell effector
      functions, at least not under the normal physiological conditions associated with
      either of these two acute viral infections.

PMID- 17215525
TI  - Images in clinical medicine. Complication of central venous catheterization.

PMID- 17215524
TI  - Role of human neutrophil peptides in the initial interaction between lung
      epithelial cells and CD4+ lymphocytes.
AB  - Human neutrophil peptides (HNP) exert immune-modulating effects. We hypothesized
      that HNP link innate and adaptive immunity through activation of costimulatory
      molecules. Human lung epithelial cells and CD4+ lymphocytes were treated with HNP
      separately or in coculture. Stimulation with HNP induced an increase in cell
      surface expression of CD54 (ICAM-1), CD80, and CD86 on lung epithelial cells and
      the corresponding major ligands, CD11a (LFA-1), CD152 (CTLA-4), and CD28 on CD4+
      lymphocytes. There was an increased nuclear expression of the transcription
      factor p53 in human alveolar A549 cells and an elevated NF-kappaB (p50) and a
      degradation of I-kappaB protein in CD4+ lymphocytes following HNP stimulation.
      HNP enhanced the interaction between A549 cells and CD4+ lymphocytes by
      increasing cell adhesion and release of IFN-gamma, IL-2, and IL-8. This was
      attenuated by using an alpha1-proteinase inhibitor to neutralize HNP. We conclude
      that HNP play an important role in linking innate to acquired immunity by
      activation of costimulatory molecules in lung epithelial cells and CD4+
      lymphocytes.

PMID- 17215526
TI  - Sex, drugs, prisons, and HIV.

PMID- 17215527
TI  - Concurrent sentences--dialysis in the state penitentiary.

PMID- 17215528
TI  - The control of pertussis--2007 and beyond.

PMID- 17215529
TI  - Sunitinib versus interferon alfa in metastatic renal-cell carcinoma.
AB  - BACKGROUND: Since sunitinib malate has shown activity in two uncontrolled studies
      in patients with metastatic renal-cell carcinoma, a comparison of the drug with
      interferon alfa in a phase 3 trial is warranted. METHODS: We enrolled 750
      patients with previously untreated, metastatic renal-cell carcinoma in a
      multicenter, randomized, phase 3 trial to receive either repeated 6-week cycles
      of sunitinib (at a dose of 50 mg given orally once daily for 4 weeks, followed by
      2 weeks without treatment) or interferon alfa (at a dose of 9 MU given
      subcutaneously three times weekly). The primary end point was progression-free
      survival. Secondary end points included the objective response rate, overall
      survival, patient-reported outcomes, and safety. RESULTS: The median progression
      free survival was significantly longer in the sunitinib group (11 months) than in
      the interferon alfa group (5 months), corresponding to a hazard ratio of 0.42
      (95% confidence interval, 0.32 to 0.54; P<0.001). Sunitinib was also associated
      with a higher objective response rate than was interferon alfa (31% vs. 6%,
      P<0.001). The proportion of patients with grade 3 or 4 treatment-related fatigue
      was significantly higher in the group treated with interferon alfa, whereas
      diarrhea was more frequent in the sunitinib group (P<0.05). Patients in the
      sunitinib group reported a significantly better quality of life than did patients
      in the interferon alfa group (P<0.001). CONCLUSIONS: Progression-free survival
      was longer and response rates were higher in patients with metastatic renal-cell
      cancer who received sunitinib than in those receiving interferon alfa
      (ClinicalTrials.gov numbers, NCT00098657 and NCT00083889 [ClinicalTrials.gov]).

PMID- 17215530
TI  - Sorafenib in advanced clear-cell renal-cell carcinoma.
AB  - BACKGROUND: We conducted a phase 3, randomized, double-blind, placebo-controlled
      trial of sorafenib, a multikinase inhibitor of tumor-cell proliferation and
      angiogenesis, in patients with advanced clear-cell renal-cell carcinoma. METHODS:
      From November 2003 to March 2005, we randomly assigned 903 patients with renal
      cell carcinoma that was resistant to standard therapy to receive either
      continuous treatment with oral sorafenib (at a dose of 400 mg twice daily) or
      placebo; 451 patients received sorafenib and 452 received placebo. The primary
      end point was overall survival. A single planned analysis of progression-free
      survival in January 2005 showed a statistically significant benefit of sorafenib
      over placebo. Consequently, crossover was permitted from placebo to sorafenib,
      beginning in May 2005. RESULTS: At the January 2005 cutoff, the median
      progression-free survival was 5.5 months in the sorafenib group and 2.8 months in
      the placebo group (hazard ratio for disease progression in the sorafenib group,
      0.44; 95% confidence interval [CI], 0.35 to 0.55; P<0.01). The first interim
      analysis of overall survival in May 2005 showed that sorafenib reduced the risk
      of death, as compared with placebo (hazard ratio, 0.72; 95% CI, 0.54 to 0.94;
      P=0.02), although this benefit was not statistically significant according to the
      O'Brien-Fleming threshold. Partial responses were reported as the best response
      in 10% of patients receiving sorafenib and in 2% of those receiving placebo
      (P<0.001). Diarrhea, rash, fatigue, and hand-foot skin reactions were the most
      common adverse events associated with sorafenib. Hypertension and cardiac
      ischemia were rare serious adverse events that were more common in patients
      receiving sorafenib than in those receiving placebo. CONCLUSIONS: As compared
      with placebo, treatment with sorafenib prolongs progression-free survival in
      patients with advanced clear-cell renal-cell carcinoma in whom previous therapy
      has failed; however, treatment is associated with increased toxic effects.
      (ClinicalTrials.gov number, NCT00073307 [ClinicalTrials.gov].).

PMID- 17215531
TI  - Response to antiretroviral therapy after a single, peripartum dose of nevirapine.
AB  - BACKGROUND: A single dose of nevirapine during labor reduces perinatal
      transmission of human immunodeficiency virus type 1 (HIV-1) but often leads to
      viral nevirapine resistance mutations in mothers and infants. METHODS: We studied
      the response to nevirapine-based antiretroviral treatment among women and infants
      who had previously been randomly assigned to a single, peripartum dose of
      nevirapine or placebo in a trial in Botswana involving the prevention of the
      transmission of HIV-1 from mother to child. All women were treated with antenatal
      zidovudine. The primary end point for mothers and infants was virologic failure
      by the 6-month visit after initiation of antiretroviral treatment, estimated
      within groups by the Kaplan-Meier method. RESULTS: Of 218 women who started
      antiretroviral treatment, 112 had received a single dose of nevirapine and 106
      had received placebo. By the 6-month visit after the initiation of antiretroviral
      treatment, 5.0% of the women who had received placebo had virologic failure, as
      compared with 18.4% of those who had received a single dose of nevirapine
      (P=0.002). Among 60 women starting antiretroviral treatment within 6 months after
      receiving placebo or a single dose of nevirapine, no women in the placebo group
      and 41.7% in the nevirapine group had virologic failure (P<0.001). In contrast,
      virologic failure rates did not differ significantly between the placebo group
      and the nevirapine group among 158 women starting antiretroviral treatment 6
      months or more post partum (7.8% and 12.0%, respectively; P=0.39). Thirty infants
      also began antiretroviral treatment (15 in the placebo group and 15 in the
      nevirapine group). Virologic failure by the 6-month visit occurred in
      significantly more infants who had received a single dose of nevirapine than in
      infants who had received placebo (P<0.001). Maternal and infant findings did not
      change qualitatively by 12 and 24 months after the initiation of antiretroviral
      treatment. CONCLUSIONS: Women who received a single dose of nevirapine to prevent
      perinatal transmission of HIV-1 had higher rates of virologic failure with
      subsequent nevirapine-based antiretroviral therapy than did women without
      previous exposure to nevirapine. However, this applied only when nevirapine-based
      antiretroviral therapy was initiated within 6 months after receipt of a single,
      peripartum dose of nevirapine. (ClinicalTrials.gov number, NCT00197587
      [ClinicalTrials.gov].).

PMID- 17215532
TI  - Inhibition of microsomal triglyceride transfer protein in familial
      hypercholesterolemia.
AB  - BACKGROUND: Patients with homozygous familial hypercholesterolemia have markedly
      elevated cholesterol levels, which respond poorly to drug therapy, and a very
      high risk of premature cardiovascular disease. Inhibition of the microsomal
      triglyceride transfer protein may be effective in reducing cholesterol levels in
      these patients. METHODS: We conducted a dose-escalation study to examine the
      safety, tolerability, and effects on lipid levels of BMS-201038, an inhibitor of
      the microsomal triglyceride transfer protein, in six patients with homozygous
      familial hypercholesterolemia. All lipid-lowering therapies were suspended 4
      weeks before treatment. The patients received BMS-201038 at four different doses
      (0.03, 0.1, 0.3, and 1.0 mg per kilogram of body weight per day), each for 4
      weeks, and returned for a final visit after a 4-week drug washout period.
      Analysis of lipid levels, safety laboratory analyses, and magnetic resonance
      imaging of the liver for fat content were performed throughout the study.
      RESULTS: All patients tolerated titration to the highest dose, 1.0 mg per
      kilogram per day. Treatment at this dose decreased low-density lipoprotein (LDL)
      cholesterol levels by 50.9% and apolipoprotein B levels by 55.6% from baseline
      (P<0.001 for both comparisons). Kinetic studies showed a marked reduction in the
      production of apolipoprotein B. The most serious adverse events were elevation of
      liver aminotransferase levels and accumulation of hepatic fat, which at the
      highest dose ranged from less than 10% to more than 40%. CONCLUSIONS: Inhibition
      of the microsomal triglyceride transfer protein by BMS-201038 resulted in the
      reduction of LDL cholesterol levels in patients with homozygous familial
      hypercholesterolemia, owing to reduced production of apolipoprotein B. However,
      the therapy was associated with elevated liver aminotransferase levels and
      hepatic fat accumulation.

PMID- 17215533
TI  - Release from prison--a high risk of death for former inmates.
AB  - BACKGROUND: The U.S. population of former prison inmates is large and growing.
      The period immediately after release may be challenging for former inmates and
      may involve substantial health risks. We studied the risk of death among former
      inmates soon after their release from Washington State prisons. METHODS: We
      conducted a retrospective cohort study of all inmates released from the
      Washington State Department of Corrections from July 1999 through December 2003.
      Prison records were linked to the National Death Index. Data for comparison with
      Washington State residents were obtained from the Wide-ranging OnLine Data for
      Epidemiologic Research system of the Centers for Disease Control and Prevention.
      Mortality rates among former inmates were compared with those among other state
      residents with the use of indirect standardization and adjustment for age, sex,
      and race. RESULTS: Of 30,237 released inmates, 443 died during a mean follow-up
      period of 1.9 years. The overall mortality rate was 777 deaths per 100,000 person
      years. The adjusted risk of death among former inmates was 3.5 times that among
      other state residents (95% confidence interval [CI], 3.2 to 3.8). During the
      first 2 weeks after release, the risk of death among former inmates was 12.7 (95%
      CI, 9.2 to 17.4) times that among other state residents, with a markedly elevated
      relative risk of death from drug overdose (129; 95% CI, 89 to 186). The leading
      causes of death among former inmates were drug overdose, cardiovascular disease,
      homicide, and suicide. CONCLUSIONS: Former prison inmates were at high risk for
      death after release from prison, particularly during the first 2 weeks.
      Interventions are necessary to reduce the risk of death after release from
      prison.

PMID- 17215534
TI  - Clinical practice. Concussion.

PMID- 17215535
TI  - Images in clinical medicine. Prevertebral emphysema after a dental procedure.

PMID- 17215536
TI  - Case records of the Massachusetts General Hospital. Case 1-2007. A 40-year-old
      woman with epistaxis, hematemesis, and altered mental status.

PMID- 17215537
TI  - Salvation by registration.

PMID- 17215538
TI  - Renal-cell carcinoma--molecular pathways and therapies.

PMID- 17215539
TI  - MODS assay for the diagnosis of TB.

PMID- 17215540
TI  - Refining prognosis in non-small-cell lung cancer.

PMID- 17215541
TI  - Survivors of childhood cancer.

PMID- 17215542
TI  - Case 31-2006: a girl with severe obesity.

PMID- 17215543
TI  - Injuries after a typhoon in China.

PMID- 17215544
TI  - Prisons and mental health.

PMID- 17215545
TI  - Validation of sperm counting methods using limits of agreement.

PMID- 17215546
TI  - Decreased semen volume and spermatozoa motility in HIV-1-infected patients under
      antiretroviral treatment.
AB  - Inconsistent results have been reported for the semen quality in HIV-infected
      men, due to the biases inherent in some studies. The objective of the present
      study was to investigate the semen parameters in HIV-1-infected patients and to
      compare their sperm characteristics with those of a control group of fertile,
      noninfected men. Factors implicated in semen alterations in HIV-1 patients were
      also analyzed. HIV-infected men (n=190), of whom 91% were undergoing
      antiretroviral therapy, and 218 fertile men were studied. Infertility risk
      factors were recorded and clinical examinations were performed for both groups.
      Records of history of HIV infection, antiretroviral treatment, and HIV-1 RNA
      detection in the blood as well as HIV-1 genome detection in the semen were
      obtained for the infected patients. Semen volumes, percentages of progressive
      motile spermatozoa, total sperm counts, and polymorphonuclear cell counts were
      decreased, while the pH values and spermatozoa multiple anomaly indices were
      increased in HIV-infected patients. Even after adjustment for possible sources of
      bias, the decreases in semen volume and progressive motility and the increase in
      pH remained significant. The present study demonstrates sperm motility and
      ejaculate volume alterations in HIV-1-infected patients, most of whom were
      receiving antiretroviral therapy. In HIV-1 patients, further longitudinal studies
      are required to analyze the impact of treatment regimen on sperm parameter
      alterations.

PMID- 17215547
TI  - Control of matrix effects in the analysis of urinary F2-isoprostanes using novel
      multidimensional solid-phase extraction and LC-MS/MS.
AB  - F(2)-isoprostanes (F(2)-iPs), established markers of oxidative stress, exist as
      four sets of regioisomers. Simultaneous and specific determination of F(2)-iPs
      can be achieved by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We
      developed novel methods for urine sample preparation and HPLC to control matrix
      related ion suppression effects in the LC-MS/MS analysis of F(2)-iPs. A selective
      solid-phase extraction (SPE) wash protocol was developed with an Oasis HLB
      (hydrophilic-lipophilic balance) SPE cartridge using an elution profile of
      [(3)H]8-iso-prostaglandin (PG)F(2alpha) (iPF(2alpha)-III) when the methanol
      concentration was increased under acidic, neutral, and base wash conditions. A
      multidimensional (MD)-SPE method that incorporated size exclusion chromatography
      [corrected] reverse-phase chromatography, and normal-phase chromatography was
      developed using an Oasis HLB SPE cartridge and an HLB microElution SPE plate.
      Average extraction recoveries of the deuterated internal standards of iPF(2alpha)
      III and iPF(2alpha)-VI were 62 +/- 8% and 60 +/- 10%. A buffer-free HPLC method
      for the separation of F(2)-iP isomers was developed on base-deactivated C8
      columns. Average matrix effects for iPF(2alpha)-III and iPF(2alpha)-VI were 95 +/
      6% and 103 +/- 5%. The clean extraction of urine F(2)-iPs using MD-SPE and the
      separation of F(2)-iP isomers using a novel HPLC method did not cause apparent
      ion suppression in the analysis of iPF(2alpha)-III and iPF(2alpha)-VI using LC
      MS/MS. These findings should be useful for establishing a routine LC-MS/MS method
      for the analysis of F(2)-iPs.

PMID- 17215548
TI  - Parameter determination for a computer simulation model of a diver and a
      springboard.
AB  - This study used kinematic data on springboard diving performances to estimate
      viscoelastic parameters of a planar model of a springboard and diver with
      wobbling masses in the trunk, thigh, and calf segments and spring dampers acting
      at the heel, ball, and toe of the foot segment. A subject-specific angle-driven
      eight-segment model was used with an optimization algorithm to determine
      viscoelastic parameter values by matching simulations to four diving
      performances. Using the parameters determined from the matching of a single dive
      in a simulation of another dive resulted in up to 31% difference between
      simulation and performance, indicating the danger of using too small a set of
      kinematic data. However, using four dives in a combined matching process to
      obtain a common set of parameters resulted in a mean difference of 8.6%. Because
      these four dives included very different rotational requirements, it is
      anticipated that the combined parameter set can be used with other dives from
      these two groups.

PMID- 17215549
TI  - Energy absorption as a predictor of leg impedance in highly trained females.
AB  - Although leg spring stiffness represents active muscular recruitment of the lower
      extremity during dynamic tasks such as hopping and running, the joint-specific
      characteristics comprising the damping portion of this measure, leg impedance,
      are uncertain. The purpose of this investigation was to assess the relationship
      between leg impedance and energy absorption at the ankle, knee, and hip during
      early (impact) and late (stabilization) phases of landing. Twenty highly trained
      female dancers (age = 20.3 +/- 1.4 years, height = 163.7 +/- 6.0 cm, mass = 62.1
      +/- 8.1 kg) were instrumented for biomechanical analysis. Subjects performed
      three sets of double-leg landings from under preferred, stiff, and soft landing
      conditions. A stepwise linear regression analysis revealed that ankle and knee
      energy absorption at impact, and knee and hip energy absorption during the
      stabilization phases of landing explained 75.5% of the variance in leg impedance.
      The primary predictor of leg impedance was knee energy absorption during the
      stabilization phase, independently accounting for 55% of the variance. Future
      validation studies applying this regression model to other groups of individuals
      are warranted.

PMID- 17215550
TI  - Age-related differences in muscle power during single-step balance recovery.
AB  - The purpose of this study was to investigate age-related differences in muscle
      power during a surrogate task of trip recovery. Participants included 10 healthy
      young men (19-23 years old) and 10 healthy older men (65-83). The task involved
      releasing participants from a forward-leaning posture. After release,
      participants attempted to recover their balance using a single step of the right
      foot. Muscle power at the hip, knee, and ankle of the stepping limb were
      determined from the product of joint angular velocity and joint torque. Muscle
      powers during balance recovery followed a relatively consistent pattern in both
      young and older men, and showed effects of both lean and age. Interestingly, the
      effects of age did not always involve smaller peak power values in the older men
      as expected from the well-documented loss of muscle power with aging. Older men
      exhibited smaller peak muscle power at the knee and larger peak muscle power at
      the ankle and hip compared to young men. The increases in muscle power at the
      ankle and hip may result from a neuromuscular adaptation aimed at improving
      balance recovery ability by compensating for the age-related loss of muscle
      function.

PMID- 17215551
TI  - The effect of muscular pre-tensing on the sprint start.
AB  - Pre-tensed and conventional starts that exert, respectively, large and small
      forces against the starting blocks in the "set" position (0.186 vs. 0.113 N per
      newton of body weight) were analyzed. The starts were videotaped, and the
      horizontal forces exerted on feet and hands were obtained from separate force
      plates. In the pre-tensed start, the legs received larger forward impulses early
      in the acceleration (0.18 vs. 0.15 N x s per kilogram of mass in the first 0.05
      s), but the hands received larger backward impulses (-0.08 vs. -0.04 N x s x kg(
      1)). At the end of the acceleration phase, there was no significant difference in
      horizontal velocity between the two types of start and only trivial differences
      in the center of mass positions. The results did not show a clear performance
      change when the feet were pressed hard against the blocks while waiting for the
      gun.

PMID- 17215552
TI  - Recoil effect of the ice hockey stick during a slap shot.
AB  - The purpose of this study was to examine the "recoil" effect of the ice hockey
      stick shaft during a stationary slap shot. Nine male adult subjects (four elite
      and five recreational) were tested. Their performances were evaluated by
      simultaneously recording stick movement and internal bending from high-speed
      digital video (1,000 Hz) and puck acceleration from a triaxial accelerometer
      positioned inside the puck. In addition, an electrical circuit measured blade
      puck contact time. Data were analyzed with a one-way MANOVA for several dependent
      variables, including final puck velocity, puck acceleration, maximum stick shaft
      bending (angle and distance deflection), stick shaft angular velocities, blade
      puck contact time, and corresponding time events. The results indicate the
      following. First, blade-puck contact time was greater for the elite than for
      recreational players (38 +/- 9 ms and 27 +/- 5 ms); however, measures for puck
      acceleration were essentially the same (63.8 g +/- 9.9 and 61.8 g +/- 19.5). Two,
      the elite players were able to generate greater puck velocities (120 +/- 18 km/h
      and 80.3 +/- 11.6 km/h). Three, the recoil timing was found to be reater for
      elite players (59.8% of blade-puck contact).

PMID- 17215553
TI  - Constitutive modeling of cartilaginous tissues: a review.
AB  - An important and longstanding field of research in orthopedic biomechanics is the
      elucidation and mathematical modeling of the mechanical response of cartilaginous
      tissues. Traditional approaches have treated such tissues as continua and have
      described their mechanical response in terms of macroscopic models borrowed from
      solid mechanics. The most important of such models are the biphasic and single
      phase viscoelastic models, and the many variations thereof. These models have
      reached a high level of maturity and have been successful in describing a wide
      range of phenomena. An alternative approach that has received considerable recent
      interest, both in orthopedic biomechanics and in other fields, is the description
      of mechanical response based on consideration of a tissue's structure--so-called
      microstructural modeling. Examples of microstructurally based approaches include
      fibril-reinforced biphasic models and homogenization approaches. A review of both
      macroscopic and microstructural constitutive models is given in the present work.

PMID- 17215554
TI  - Normalization of ground reaction forces.
AB  - The appropriateness of normalizing data, as one method to reduce the effects of a
      covariate on a dependent variable, should be evaluated. Using ratio, 0.67
      nonlinear, and fitted normalizations, the aim of this study was to investigate
      the relationship between ground reaction force variables and body mass (BM).
      Ground reaction forces were recorded for 40 female subjects running at 3.7 +/-
      0.18 m x s(-1) (mass = 58 +/- 6 kg). The explained variance for mass to forces
      (peak-impact-vertical = 70%; propulsive-vertical = 27%; braking = 40%) was
      reduced to <0.1% for mass to ratio normalized forces (i.e., forces/BM1) with
      statistically significantly different power exponents (p < 0.05). The smaller
      covariate effect of mass on loading rate variables of 2-16% was better removed
      through fitted normalization (e.g., vertical-instantaneous-loading rate/
      BM(0.69+/-0.93); +/-95% CI) with nonlinear power exponents ranging from 0.51 to
      1.13. Generally, these were similar to 0.67 as predicted through dimensionality
      theory, but, owing to the large confidence intervals, these power exponents were
      not statistically significantly different from absolute or ratio normalized data
      (p > 0.05). Further work is warranted to identify the appropriate method to
      normalize loading rates either to mass or to another covariate. Ratio
      normalization of forces to mass, as predicted through Newtonian mechanics, is
      recommended for comparing subjects of different masses.

PMID- 17215555
TI  - Measurement of in vivo lumbar intervertebral disc pressure during spinal
      manipulation: a feasibility study.
AB  - This paper presents the first reported measurements of lumbar intervertebral disc
      pressure in vivo during spinal manipulation. A pressure transducer was inserted
      into the nucleus pulposus of one normal-appearing lumbar disc in an asymptomatic
      adult volunteer. Pressures were recorded during several body positions and
      maneuvers, then during spinal manipulation, and lastly during a repetition of the
      preintervention body positions. Baseline pressures in the prone and side-lying
      positions measured 110 kPa and 150 kPa, respectively. During the manipulation,
      pressure rose to a peak of 890 kPa over 250 ms. Immediately following, pressures
      in the prone and side-lying positions measured 150 kPa and 165 kPa, respectively.
      These data do not support the hypotheses that manipulation can reduce a
      herniation by decreasing intradiscal pressure, or cause a herniation by raising
      pressure to failure levels. Further work may lead to a better understanding of
      this treatment method.

PMID- 17215556
TI  - Competitive sport and aging: the need for qualitative sociological research.
AB  - The number of older athletes is growing with the aging of populations across the
      developed world. This article reviews studies from a variety of disciplines that
      focus specifically on the motives and experiences of older adults competing in
      physically demanding sports at events such as masters and veterans competitions
      in Australia or the Senior Olympics in North America. It is shown that the
      majority of research into this phenomenon has taken a quantitative approach or
      failed to consider older athletes' experiences in the context of broader
      sociocultural discourses. Therefore, using the author's research into the
      experiences of older Australian masters athletes as a catalyst, the need for and
      strength of sociological qualitative research in this area is discussed. The use
      of qualitative methods, such as in-depth interviews and observations, and
      interpretive analysis provided alternative ways of making sense of older adults
      and their relationship with competitive sport to what is typically found in the
      sport and aging literature.

PMID- 17215557
TI  - "There's more to life than just walking": older women's ways of staying healthy
      and happy.
AB  - This study assessed a range of activities reported by older women in Australia.
      Women between 75 and 81 years of age (N = 3,955) from the older cohort of the
      Australian Longitudinal Study on Women's Health responded to a request in a self
      report survey for additional information concerning their health. Of these 3,955
      women, 509 reported taking part in a variety of activities. Qualitative analysis
      of responses identified 55 coded categories of activities that were subsequently
      classified into four major themes: physical activities, creative pursuits,
      lifestyle, and social interaction. The data show that these older women are
      taking part in a wide range of activities.

PMID- 17215558
TI  - Leisure-time physical activity and health-care utilization in older adults.
AB  - This study examined whether leisure-time physical activity (LTPA) was associated
      with health-care utilization in a racially diverse sample of rural and urban
      older adults. Community-dwelling adults (N = 1,000, 75.32 +/- 6.72 years old)
      self-reported participating in LTPA and their use of the health-care system
      (physician visits, number and length of hospitalizations, and emergency-room
      visits). After controlling for variables associated with health and health-care
      utilization, older adults who reported lower levels of LTPA also reported a
      greater number of nights in the hospital in the preceding year. There was no
      support, however, for a relationship between LTPA and the other indicators of
      health-care utilization. Our findings suggest that being physically active might
      translate to a quicker recovery for older adults who are hospitalized. Being
      physically active might not only have health benefits for older persons but also
      lead to lower health-care costs.

PMID- 17215559
TI  - Muscle-power quality: does sex or race affect movement velocity in older adults?
AB  - To determine sex and race differences in muscle power per unit of muscle
      contraction, knee-extensor muscle power normalized for knee-extensor muscle
      volume was measured in 79 middle-aged and older adults (30 men and 49 women, age
      range 50-85 years). Results revealed that women displayed a 38% faster peak
      movement velocity than men and African Americans had a 14% lower peak movement
      velocity than Whites of a similar age when expressed per unit of involved muscle
      (p < .001). As expected, men exhibited greater knee-extensor strength and peak
      power per unit of muscle than women, but women had a faster knee- extension
      movement velocity per unit of muscle than men at the same relative strength
      level. Moreover, African Americans had greater knee-extensor muscle volume than
      Whites but exhibited lower knee-extensor strength and lower movement velocity per
      unit of muscle when tested at the same relative strength levels.

PMID- 17215560
TI  - Correlates of physical activity in a community sample of older adults in
      Appalachia.
AB  - Although much has been learned about the global determinants of physical activity
      in adults, there has been a lack of specific focus on gender, age, and
      urban/rural differences. In this church-based community sample of Appalachian
      adults (N = 1,239), the primary correlates of physical activity included age,
      gender, obesity, and self-efficacy. Overall, 42% of all participants and 31% of
      adults age 65 years or older met recommended guidelines for physical activity,
      which suggests that most participants do not engage in adequate levels of
      physical activity. Of participants who met physical activity guidelines, the most
      common modes of moderate and vigorous activity were walking briskly or uphill,
      heavy housework or gardening, light strength training, and biking. These
      particular activities that focus on building self-efficacy might be viable
      targets for intervention among older adults in rural communities.

PMID- 17215561
TI  - Community exercise program for older adults recovering from hip fracture: a pilot
      study.
AB  - Community-based rehabilitative exercise programs might be an effective means to
      improve functional outcomes for hip-fracture patients. The purpose of this study
      was to evaluate the effectiveness of a community exercise program (CEP) for older
      adults recovering from hip fracture. Twenty-five older adults (mean age 80.0 +/-
      6.0 years; 24 women; 71 +/- 23 days post-hip fracture) participated in this pilot
      study (17 exercise, 8 control). The CEP involved functional stepping and lower
      extremity-strengthening exercises. Control participants received only standard
      outpatient therapy. Measures of functional mobility, balance confidence, falls
      efficacy, lower extremity strength, and daily physical activity were evaluated at
      baseline and at 16 weeks. Improvements for self-reported physical activity,
      mobility, balance, and knee-extensor strength were observed for the CEP group.
      This study demonstrated that a CEP is beneficial for community-dwelling older
      adults post-hip fracture.

PMID- 17215562
TI  - Definitions of sedentary in physical-activity-intervention trials: a summary of
      the literature.
AB  - This review describes the definitions of sedentary used to screen community
      dwelling adults in physical-activity-intervention trials published from 2000 to
      2005. Results of 42 trials showed that definitions of sedentary varied from <20
      to <150 min/week of physical activity, and few reported the type (work,
      household, or leisure) or intensity of activity that was used to screen
      participants. The range of "sedentary" samples makes it difficult to compare
      trial results or generalize findings. Published reports of exercise trials would
      be more useful to practitioners and researchers if they included an explicit
      description of the cut point used to define sedentary adults in the sample, in
      terms of maximum minutes or days per week of activity and the wording of the
      screening measure in terms of type and intensity of activity.

PMID- 17215563
TI  - Attitudes, order and quantity: deterministic and direct probabilistic tests of
      unidimensional unfolding.
AB  - This article is the final in the series on unidimensional unfolding. The
      investigations of Kyngdon (2006b) and Michell (1994) were extended to include
      direct probabilistic tests of the quantitative and ordinal components of
      unfolding theory with the multinomial Dirichlet model (Karabatsos 2005); and
      tests of the higher order axiomatic conjoint measurement (ACM, Krantz, Luce,
      Suppes and Tversky (KLST) 1971) condition of triple cancellation. Strong
      Dirichlet model support for both the ordinal and quantitative components of
      unfolding was only found in datasets that satisfied at least double cancellation.
      In contrast, the Item Response Theory (IRT) simple hyperbolic cosine model for
      pairwise preferences (SHCMpp, Andrich 1995) fitted all datasets. The paper
      concluded the SHCMpp is suited to the instrumental rather than scientific task
      (Michell 2000) of psychological measurement; with the caveat of the problematic
      chi square fit statistic. The paper also presents original work by the second
      author on coherent tests of triple cancellation.

PMID- 17215564
TI  - Conception and construction of a Rasch-scaled measure for self-confidence in
      one's vocabulary ability.
AB  - Although different theoretical approaches indicate the importance of self
      confidence in one's ability in educational or counselling psychology, there are
      only a few standardized psychological instruments, these being mainly
      questionnaires, that focus on this construct. The idea pursued is to expand a
      traditional ability test and create an objective personality measure for self
      confidence in one's ability. Empirical evidence will be provided as to whether it
      is possible to construct and cross validate this measure using the Rasch model. A
      two step procedure allowing for a self rating of one's knowledge of words was
      designed using 25 items from a general knowledge - vocabulary test. The results
      indicate that it is possible to construct and cross validate a measure for self
      confidence in one's ability using the Rasch model. Additionally, it is shown that
      the measure for self-confidence in one's ability is independent from the general
      knowledge.

PMID- 17215566
TI  - Bookmark locations and item response model selection in the presence of local
      item dependence.
AB  - The bookmark standard setting procedure is a popular method for setting
      performance standards on state assessment programs. This study reanalyzed data
      from an application of the bookmark procedure to a passage-based test that used
      the Rasch model to create the item ordered booklet. Several problems were noted
      in this implementation of the bookmark procedure, including disagreement among
      the SMEs about the correct order of items in the bookmark booklet, performance
      level descriptions of the passing standard being based on passage difficulty as
      well as item difficulty, and the presence of local item dependence within reading
      passages. Bookmark item locations were recalculated for the IRT three-parameter
      model and the multidimensional bifactor model. The results showed that the order
      of item locations was very similar for all three models when items of high
      difficulty and low discrimination were excluded. However, the items whose
      positions were the most discrepant between models were not the items that the
      SMEs disagreed about the most in the original standard setting. The choice of
      latent trait model did not address problems of item order disagreement.
      Implications for the use of the bookmark method in the presence of local item
      dependence are discussed.

PMID- 17215565
TI  - Relative precision, efficiency and construct validity of different starting and
      stopping rules for a computerized adaptive test: the GAIN substance problem
      scale.
AB  - Substance abuse treatment programs are being pressed to measure and make clinical
      decisions more efficiently about an increasing array of problems. This
      computerized adaptive testing (CAT) simulation examined the relative efficiency,
      precision and construct validity of different starting and stopping rules used to
      shorten the Global Appraisal of Individual Needs' (GAIN) Substance Problem Scale
      (SPS) and facilitate diagnosis based on it. Data came from 1,048 adolescents and
      adults referred to substance abuse treatment centers in 5 sites. CAT performance
      was evaluated using: (1) average standard errors, (2) average number of items,
      (3) bias in person measures, (4) root mean squared error of person measures, (5)
      Cohen's kappa to evaluate CAT classification compared to clinical classification,
      (6) correlation between CAT and full-scale measures, and (7) construct validity
      of CAT classification vs. clinical classification using correlations with five
      theoretically associated instruments. Results supported both CAT efficiency and
      validity.

PMID- 17215567
TI  - Comparing concurrent versus fixed parameter equating with common items: using the
      dichotomous and partial credit models in a mixed-item format test.
AB  - There has been some discussion among researchers as to the benefits of using one
      calibration process over the other during equating. Although literature is rife
      with the pros and cons of the different methods, hardly any research has been
      done on anchoring (i.e., fixing item parameters to their pre-determined values on
      an established scale) as a method that is commonly used by psychometricians in
      large-scale assessments. This simulation research compares the fixed form of
      calibration with the concurrent method (where calibration of the different forms
      on the same scale is accomplished by a single run of the calibration process,
      treating all non-included items on the forms as missing or not reached), using
      the dichotomous Rasch (Rasch, 1960) and the Rasch partial credit (Masters, 1982)
      models, and the WINSTEPS (Linacre, 2003) computer program. Contrary to the belief
      and some researchers' contention that the concurrent run with larger n-counts for
      the common items would provide greater accuracy in the estimation of item
      parameters, the results of this paper indicate that the greater accuracy of one
      method over the other is confounded by the sample-size, the number of common
      items, etc., and there is no real benefit in using one method over the other in
      the calibration and equating of parallel tests forms.

PMID- 17215568
TI  - Instrument development tools and activities for measure validation using Rasch
      models: part I - instrument development tools.
AB  - Instrument development is an arduous task that, if undertaken with care and
      consideration, can lay the foundation for the development of validity arguments
      relating to the inferences and decisions that are based on test measures. This
      article, Part I of a two-part series, provides an overview of validity concepts
      and describes how instrument development efforts can be conducted to facilitate
      the development of validity arguments. Our discussion focuses on documentation of
      the purpose of measurement, creation of test specifications, item development,
      expert review, and planning of pilot studies. Through these instrument
      development activities and tools, essential information is documented that will
      feed into the analysis, summary, and reporting of data relevant to validity
      arguments discussed in Part II of this series.

PMID- 17215569
TI  - Utility of fiberoptic bronchoscopy for retrieval of aspirated headscarf pins.
AB  - BACKGROUND: Headscarf pin aspiration is a common and unique form of foreign body
      aspiration among young Moslem women. Rigid bronchoscopy (RB) is considered the
      standard procedure for retrieval. There are little data on the role of flexible
      fiberoptic bronchoscopy (FOB) in the retrieval of aspirated headscarf pins.
      OBJECTIVES: The aim of this study is to prospectively evaluate the utility of FOB
      for the retrieval of aspirated headscarf pins. METHODS: Patients with the
      diagnosis of headscarf pin aspiration admitted to King Abdullah University
      Hospital from December 2002 to December 2005 were included in the study. Standard
      FOB procedure under local anesthesia and conscious sedation was performed as the
      primary tool for retrieval. RESULTS: A total of 16 cases was admitted during the
      study period. The mean age was 19 years. The aspirated pin was successfully
      retrieved in 9/16 cases (56%) during the first attempt of FOB. In another 3
      cases, although the pin was successfully retrieved from the bronchial tree, it
      was lost in the throat and swallowed, and then recovered by
      esophagogastroduodenoscopy. However, FOB was not successful in 4/16 cases. In 3
      cases, the aspirated pins were successfully retrieved by RB under general
      anesthesia and the fourth case required thoracotomy. CONCLUSIONS: Headscarf pin
      aspiration is a relatively common form of foreign body aspiration among young
      Moslem Jordanian women. FOB under local anesthesia can be a useful first-step
      tool in retrieval, provided facilities for esophagogastroduodenoscopy and RB are
      readily available.

PMID- 17215570
TI  - Two cases of ampulla (takotsubo-shaped) cardiomyopathy associated with
      hemophagocytic lymphohistiocytosis.
AB  - There have been many reports of patients with ampulla cardiomyopathy described as
      takotsubo-shaped cardiomyopathy in the cardiovascular field. This unique
      cardiomyopathy is characterized by transient apical ballooning and hypokinesis of
      the left ventricle. We describe 2 cases of ampulla cardiomyopathy associated with
      hemophagocytic lymphohistiocytosis (HLH). In both of the patients, ventricular
      dysfunction suddenly occurred during the active phase of HLH. In each case, the
      findings on ECG, echocardiogram and left ventriculogram were compatible with
      ampulla cardiomyopathy. To our knowledge, this communication is the first to
      report cases of ampulla cardiomyopathy associated with HLH. Our cases suggest
      that HLH hypercytokinemia may have a role in causing ampulla cardiomyopathy.

PMID- 17215571
TI  - Catheter lock solutions to prevent bloodstream infections in high-risk
      hemodialysis patients.
AB  - BACKGROUND: Antimicrobial catheter lock solutions (CLS) have been shown to
      prevent bacteremia in chronic hemodialysis (HD) patients with new HD catheters.
      However, there is little information regarding the usage of these solutions in
      patients who have a history of recurrent bacteremia and are at very high risk of
      infection. The purpose of this investigation was to identify the efficacy of
      these solutions in such high-risk patients. METHODS: A retrospective chart review
      was performed to identify patients who had a history of recurrent bacteremia and
      had received prophylaxis with antimicrobial CLS. RESULTS: Nine patients with
      recurrent bacteremia were identified. These patients had received prophylaxis
      with minocycline/EDTA, gentamicin/heparin, or vancomycin/heparin solutions. The
      catheter-related bacteremia rate was 9.13 per 1,000 catheter days prior to the
      use of CLS, 1.04 during use of solution, and 7.94 after the CLS were discontinued
      (p < 0.001). CONCLUSIONS: These results show a dramatic effect of antimicrobial
      CLS on the prevention of catheter-related bacteremia.

PMID- 17215572
TI  - Indoxyl sulfate and atherosclerotic risk factors in hemodialysis patients.
AB  - BACKGROUND: Indoxyl sulfate is a uremic toxin that accelerates the progression of
      chronic kidney disease (CKD). Serum levels of indoxyl sulfate are increased in
      dialysis patients. It was reported that indoxyl sulfate plays a role in
      endothelial dysfunction in uremic patients, and stimulates proliferation of rat
      vascular smooth muscle cells (VSMC). We examined associations between indoxyl
      sulfate and several markers related to atherosclerosis. METHODS: The association
      between indoxyl sulfate and atherosclerotic risk factors was studied in 224
      hemodialysis (HD) patients (123 male, 101 female). Serum levels of indoxyl
      sulfate were measured by using high-performance liquid chromatography (HPLC).
      RESULTS: There were significant differences in serum levels of creatinine,
      calcium x phosphate and pentosidine between high- and low-indoxyl sulfate level
      groups. Indoxyl sulfate showed significant positive correlations with
      pentosidine, creatinine, and protein catabolic rate, and a significant negative
      correlation with high-density lipoprotein (HDL) cholesterol. Further,
      pentosidine, creatinine, and HDL-cholesterol were independently associated with
      indoxyl sulfate by multiple linear regression analysis. CONCLUSION: In addition
      to creatinine, pentosidine and HDL-cholesterol, the risk factors of
      atherosclerosis, were associated with indoxyl sulfate in HD patients. Indoxyl
      sulfate may be involved in the pathogenesis of atherosclerosis.

PMID- 17215573
TI  - Impact of ergocalciferol treatment of vitamin D deficiency on serum parathyroid
      hormone concentrations in chronic kidney disease.
AB  - BACKGROUND: Vitamin D deficiency is highly prevalent and associated with
      secondary hyperparathyroidism in patients with chronic kidney disease (CKD). The
      Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines recommend
      treatment of vitamin D deficiency starting with CKD stage 3, though no data are
      available showing an impact on serum parathyroid hormone (PTH) concentrations.
      The goal of this analysis, therefore, was to determine the effect of
      ergocalciferol treatment on plasma PTH concentrations in vitamin D-deficient
      patients with stage 3 and stage 4 CKD. METHODS: A prospective, nonrandomized
      observational analysis was conducted in an academic community hospital CKD
      clinic. Fifty-two patients with stage 3 or stage 4 CKD with vitamin D deficiency
      and elevated PTH concentrations received ergocalciferol dosed per a modified
      K/DOQI guidelines protocol and adjusted every 3 months. Serum PTH, 25-vitamin D,
      1,25-vitamin D, calcium, phosphorus, and albumin levels were drawn at initiation
      of therapy and repeated every 3 months. RESULTS: The mean 25-vitamin D levels
      normalized in patients with stage 3 and 4 CKD, with values of 31.6 +/- 2.2 ng/ml
      (78.8 +/- 5.49 nmol/l) and 35.4 +/- 1.9 ng/ml (88.4 +/- 4.74 nmol/l),
      respectively (p < 0.0001). A median decrease in PTH concentrations of 13.1 and
      2.0% was noted in patients with stage 3 and stage 4 CKD, respectively (p = 0.041,
      p = nonsignificant). CONCLUSIONS: Ergocalciferol therapy is a reasonable initial
      therapy for vitamin D deficiency associated with elevated PTH levels in stage 3
      CKD. It does not appear to have equivalent benefits in stage 4 CKD.

PMID- 17215574
TI  - Reactive oxygen metabolites: a link between oxidative stress and inflammation in
      patients on hemodialysis.
AB  - Oxidative stress plays a significant role in the development of inflammation in
      patients undergoing hemodialysis (HD). This study intends to evaluate the
      relationship between C-reactive protein (CRP) and the newly established marker of
      lipid peroxidation, d-ROMs (reactive oxygen metabolites), in comparison with
      different indicators of oxidative stress. Plasma total antioxidant capacity
      (TAC), lipid peroxidation products malonaldehyde (MDA) and 4-hydroxyalkenals, as
      well as d-ROMs, were determined in 24 patients before HD and in 21 normal
      controls (NC). It was found that HD patients had higher levels of d-ROMs than NC
      (p = 0.033). A highly significant positive correlation was observed between
      logCRP and d-ROMs concentrations (p < 0.0001, r = 0.85) in patients, but not in
      NC. The concentrations of TAC and MDA were not associated with CRP in HD or in NC
      individuals. It is concluded that d-ROMs concentration is a potent marker of
      oxidative injury that is strongly indicative of the inflammatory status in HD
      patients.

PMID- 17215575
TI  - Stroke research priorities for the next decade--a supplement statement on
      intracranial haemorrhage.

PMID- 17215577
TI  - Improved survival after stroke.

PMID- 17215578
TI  - Predictive value of 6-month decline in ADAS-cog for survival without severe
      Alzheimer's disease.
AB  - BACKGROUND/AIMS: To determine the predictive value of the 6-month evolution of
      the ADAS-cog score in initially mild to moderate Alzheimer's disease (AD)
      patients on the risk of death or severe dementia (MMSE <10) within 2 years.
      METHODS: Cognition was assessed every 6 months using the ADAS-cog scale in the
      Real.fr study, a cohort of AD patients. Six classes of ADAS-cog evolution were
      distinguished, from the severest deterioration (decline >or=7 points) to the
      greatest cognitive improvement (gain >or=4 points). RESULTS: Among 536 AD
      patients, 53 (9.9%) had a 6-month decline of 7 points or more. This group with
      the severest deterioration was significantly associated with the risk of severe
      dementia or death at 2 years (relative risk, RR = 3.8, 95% confidence interval,
      CI = 2.1-6.8), even after adjustment for baseline MMSE, disability and ADAS-cog
      score (RR = 2.6, 95% CI = 1.4-5.0). In addition, subjects with a decline by at
      least 4 points were also at greater risk of severe dementia. CONCLUSION: These
      results confirm the value of the ADAS-cog scale as a judgement criterion in
      clinical trials since it is a good surrogate marker of long-term prognosis. The
      proportion of fast decliners on the ADAS-cog could be a helpful judgement
      criterion for future trials in AD.

PMID- 17215579
TI  - Accounting for linkage disequilibrium among markers in linkage analysis: impact
      of haplotype frequency estimation and molecular haplotypes for a gene in a
      candidate region for Alzheimer's disease.
AB  - OBJECTIVES: Linkage disequilibrium (LD) between closely spaced SNPs can be
      accommodated in linkage analysis by specifying the multi-SNP haplotype
      frequencies, if known. Phased haplotypes in candidate regions can provide gold
      standard haplotype frequency estimates, and may be of inherent interest as
      markers. We evaluated the effects of different methods of haplotype frequency
      estimation, and the use of marker phase information, on linkage analysis of a
      multi-SNP cluster in a candidate region for Alzheimer's disease (AD). METHODS: We
      performed parametric linkage analysis of a five-SNP cluster in extended pedigrees
      to compare the use of: (1) haplotype frequencies estimated by molecular phase
      determination, maximum likelihood estimation, or by assuming linkage equilibrium
      (LE); (2) AD families or controls as the frequency source; and (3) unphased or
      molecularly phased SNP data. RESULTS: There was moderate to strong pairwise LD
      among the five SNPs. Falsely assuming LE substantially inflated the LOD score,
      but the method of haplotype frequency estimation and particular sample used made
      little difference provided that LD was accommodated. Use of phased haplotypes
      produced a modest increase in the LOD score over unphased SNPs. CONCLUSIONS:
      Ignoring LD between markers can lead to substantially inflated evidence for
      linkage in LOD score analysis of extended pedigrees with missing data. Use of
      marker phase information in linkage analysis may be important in disease studies
      where the costs of family recruitment and phenotyping greatly exceed the costs of
      phase determination.

PMID- 17215580
TI  - Robust multipoint simultaneous identical-by-descent mapping for two linked loci.
AB  - A challenging issue in genetic mapping of complex human diseases is localizing
      disease susceptibility genes when the genetic effects are small to moderate.
      There are greater complexities when multiple loci are linked to a chromosomal
      region. Liang et al. [Hum Hered 2001;51:64-78] proposed a robust multipoint
      method that can simultaneously estimate both the position of a trait locus and
      its effect on disease status by using affected sib pairs (ASPs). Based on the
      framework of generalized estimating equations (GEEs), the estimate and standard
      error of the position of a trait locus are robust to different genetic models. To
      utilize other relative pairs collected in pedigree data, Schaid et al. [Am J Hum
      Genet 2005;76:128-138] extended Liang's method to various types of affected
      relative pairs (ARPs) by two approaches: unconstrained and constrained methods.
      However, the above methods are limited to situations in which only one trait
      locus exists on the chromosome of interest. The mean functions are no longer
      correctly specified when there are multiple causative loci linked to a
      chromosomal region. To overcome this, Biernacka et al. [Genet Epidemiol
      2005;28:33-47] considered the multipoint methods for ASPs to allow for two linked
      disease genes. We further generalize the approach to cover other types of ARPs.
      To reflect realistic situations for complex human diseases, we set modest sizes
      of genetic effects in our simulation. Our results suggest that several hundred
      independent pedigrees are needed, and markers with high information, to provide
      reliable estimates of trait locus positions and their confidence intervals.
      Bootstrap resampling can correct the downward bias of the robust variance for
      location estimates. These methods are applied to a prostate cancer linkage study
      on chromosome 20 and compared with the results for the one-locus model [Am J Hum
      Genet 2005;76:128-138]. We have implemented the multipoint IBD mapping for one
      and two linked loci in our software GEEARP, which allows analyses for five
      general types of ARPs.

PMID- 17215581
TI  - Insulin-like growth factor-1, leptin, body composition, and clinical status
      interactions in children with cystic fibrosis.
AB  - BACKGROUND/AIMS: Children with cystic fibrosis (CF) are of increased risk of
      reduced fat body mass (FBM) and lean body mass (LBM). Serum concentrations of
      insulin-like growth factor-1 (IGF-1)and leptin could be markers of LBM and/or FBM
      depletion. To evaluate the relationships between disease activity, body
      composition, IGF-1 and leptin concentrations in CF children. METHODS: A cross
      sectional study with 26 CF children aged 5.0-15.5 years and 33 healthy controls,
      mean age 9.4 years. Body composition was evaluated by dual-energy X-ray
      absorptiometry. Fasting blood samples were analyzed for leptin, IGF-1 and IGFBP
      3. RESULTS: FBM standard deviation score (SDS; CF boys -0.02 +/- 0.88 vs. 0.78 +/
      0.65, p < 0.01; CF girls -0.37 +/- 1.15 vs. 0.70 +/- 0.97, p < 0.05), leptin
      concentration (CF boys 2.07 +/- 0.79 vs. 3.07 +/- 1.28 ng/ml, p < 0.05; CF girls
      2.71 +/- 0.86 vs. 5.00 +/- 2.95 ng/ml, p < 0.05) and IGF-1SDS (CF boys -1.43 +/-
      1.50 vs. -0.32 +/- 0.88, p < 0.05; CF girls -0.66 +/- 1.66 vs. 0.64 +/- 0.57, p <
      0.01) were lower in CF children compared to controls. Shwachman score was the
      strongest predictor of lean body mass (R = 0.63). Leptin levels explain 60% of
      the variability in FBM. CONCLUSION: Serum concentrations of IGF-1 and leptin are
      decreased in children with CF and are associated with clinical conditions and
      body composition.

PMID- 17215582
TI  - Effect of dietary chromium on resistance artery function and nitric oxide
      signaling in the sucrose-fed spontaneously hypertensive rat.
AB  - BACKGROUND: Consumption of high-glycemic index foods contributes to the
      development of hypertension in some patients. Likewise, in spontaneously
      hypertensive rats (SHR), high sucrose promotes a secondary rise in systolic blood
      pressure (SBP). Chromium (III) (Cr(3+)) prevents sucrose-induced hypertension,
      but leaves the basal hypertension that characterizes SHR intact. METHODS: Since
      hypertension entails increased peripheral resistance, we compared effects of
      Cr(3+) on resistance arteries from SHR fed low-glycemic (starch) versus high
      glycemic (sucrose) index diets. Subgroups of SHR also received Cr(3+). Structure,
      stiffness, and vasodilation of mesenteric resistance arteries were studied using
      pressurized myography. RESULTS: Sucrose increased SBP in SHR and, exclusively in
      sucrose-fed SHR, Cr(3+) reduced SBP and augmented acetylcholine or nitroprusside
      dependent vasodilation. Neither sucrose nor Cr(3+) affected artery structure or
      stiffness. Since Cr(3+) enhanced vasodilation, we assessed endothelial NO
      synthase (eNOS), guanylate cyclase, cGMP-dependent protein kinase (PKG-1alpha and
      1beta), and PKG activity by immunoblotting. Sucrose reduced eNOS, PKG-1beta, and
      PKG activity. Cr(3+) prevented the effects of sucrose on NO signaling.
      CONCLUSION: In hypertension exacerbated by high-glycemic index diet, Cr(3+)
      reduces SBP. The BP-lowering effect of Cr(3+), selectively on sucrose-induced but
      not basal hypertension in SHR, involves at least in part, improving vasodilatory
      function vis-a-vis restoration of NO signaling in resistance arteries.

PMID- 17215583
TI  - Magnetic resonance imaging of ruptured plaques in the rabbit with ultrasmall
      superparamagnetic particles of iron oxide.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) enhanced with ultrasmall
      superparamagnetic particles of iron oxide (USPIO) has previously been evaluated
      in hyperlipidemic rabbits. The aim of this study was therefore to compare USPIO
      in ruptured and non-ruptured arteries in an atherosclerotic rabbit model.
      METHODS: Atherosclerotic-like lesions were induced by the combination of
      endothelial abrasion and high-cholesterol diet in iliac rabbit arteries (n = 16).
      Rupture of atherosclerotic lesions was realized by oversized balloon angioplasty
      in one iliac artery, whereas the contralateral artery was used as control. USPIO
      (ferumoxtran-10: 1 mmol Fe/kg) was administered immediately (n = 10) or 28 days
      (n = 6) after injury. MRI and histological analysis were performed 7 and 35 days
      after injury and in control arteries. RESULTS: In vivo MRI analysis showed
      extended susceptibility artifact with transluminal signal loss in all ruptured
      arteries 7 days after injury. In contrast, hyposignal was reduced 35 days
      following injury (i.e. after healing), and absent in non-ruptured arteries.
      Similarly, histological analysis of iron uptake was significantly increased 7
      days after injury compared to healed-ruptured and control arteries. CONCLUSIONS:
      Accumulation ofUSPIO is significantly increased in ruptured as compared to non
      ruptured arteries in the atherosclerotic rabbit model.

PMID- 17215584
TI  - Saxatilin, a snake venom disintegrin, regulates platelet activation associated
      with human vascular endothelial cell migration and invasion.
AB  - BACKGROUND: Platelet activation results in platelet aggregation and the secretion
      of granules, which contain a variety of constituents including nonprotein
      molecules, adhesive proteins and hydrolases. The platelet-derived supernatant
      (PDS), which contains these granules, is known to trigger the activation of
      endothelium and chemotaxis of monocytes. METHODS AND RESULTS: PDS derived from
      collagen-activated platelets stimulated human umbilical vein endothelial cell
      (HUVEC) migration and invasion, as measured through the use of a Boyden chamber.
      This collagen-induced PDS also triggered integrin alpha(v)beta(3) upregulation in
      HUVECs. The inclusion of a neutralizing antibody to platelet-derived growth
      factor (PDGF)-B abolished HUVEC migration/invasion and integrin alpha(v)beta(3)
      upregulation, showing that PDGF-AB mediates the proangiogenic effects of collagen
      activated PDS. Saxatilin, a snake venom disintegrin known to interrupt platelet
      aggregation by antagonizing integrin alpha(IIb)beta(3), inhibited the collagen
      induced platelet activation and abolished the angiogenic properties of PDS.
      Saxatilin also inhibited the collagen-induced phosphorylation of Syk, a key
      mediator of inside-out signaling in platelet activation. CONCLUSION: Saxatilin
      inhibits platelet activation, platelet PDGF-AB release as well as subsequent
      endothelial cell migration and invasion.

PMID- 17215585
TI  - Functional analysis of an established mouse vascular endothelial cell line.
AB  - BACKGROUND: In vitrostudies using cell lines are useful for the understanding of
      cellular mechanisms. The purpose of our study is to develop a new immortalized
      aortic vascular endothelial cell (EC) line that retains endothelial
      characteristics and can facilitate the study of ECs. METHODS: A mouse aortic
      vascular EC line (MAEC) was established from p53-deficient mouse aorta and
      cultured for over 100 passages. The expression of endothelial markers was
      assessed, and the function of this cell line was analyzed by tube formation and
      binding assays. RESULTS: MAEC retained many endothelial properties such as
      cobblestone appearance, contact-inhibited growth, active uptake of acetylated low
      density lipoprotein, existence of Weibel-Palade bodies and several EC markers.
      MAECs exhibited tube formation activity both in vitro and in vivo. Furthermore,
      crucially, tumor necrosis factor alpha, an inflammatory cytokine, promoted
      lymphocyte adhesion to MAECs, suggesting that MAECs may facilitate the study of
      atherosclerosis and local inflammatory reactions in vitro. CONCLUSION: We
      describe the morphological and cell biological characteristics of MAEC, providing
      strong evidence that it retained endothelial properties. This novel cell line can
      be a useful tool for studying the biology of ECs.

PMID- 17215586
TI  - Hepcidin in anemia and inflammation in chronic kidney disease.
AB  - Maintaining the correct iron balance is crucial for health. Our understanding of
      the molecular control of iron metabolism has increased dramatically over the past
      5 years due to the discovery of hepcidin. This is a circulating antimicrobial
      peptide mainly synthesized in the liver, which has been recently proposed as a
      factor regulating the uptake of dietary iron and its mobilization from
      macrophages and hepatic stores. Inflammation causes an increase of production of
      hepcidin, which is a potent mediator of anemia of chronic diseases. Anemia in
      chronic kidney disease is mainly due to erythropoietin deficiency but these
      patients often have a chronic inflammatory state. The aim of this review is to
      summarize the current knowledge dealing with a possible role of hepcidin in iron
      metabolism and its regulation, particularly in kidney disease. In addition,
      current methods of determination of hepcidin are reviewed.

PMID- 17215587
TI  - Simplified electrodiagnostic criteria of diabetic polyneuropathy in field study
      (KCIS No. 14).
AB  - This study sought to determine the sensitivity of sural sensory action amplitude
      (SAP) and peroneal motor conduction velocity (MCV) for differentiating the status
      of other nerve conduction velocities and identifying important correlates of
      diabetic polyneuropathy. Subjects (n = 708) with type 2 diabetes from one
      community completed a preliminary questionnaire. Among the 298 subjects with
      positive questionnaire results, 272 completed nerve conduction tests. The means
      of 6 nerve conduction velocities of subjects with both SAP and MCV abnormalities
      were compared to those of normal controls. The mean conduction velocities of all
      motor and sensory nerves were slower (p < 0.05) in subjects with polyneuropathy
      than without polyneuropathy. Important known correlates of diabetic
      polyneuropathy can also be identified by this electrophysiological definition.
      The sural SAP and peroneal MCV together serve as a good diagnostic for diabetic
      polyneuropathy and can be used as a simplified criterion in field studies.

PMID- 17215588
TI  - Disability evolution in multiple sclerosis: how to deal with missing transition
      times in the Markov model?
AB  - Markov modeling of disability progression in multiple sclerosis requires
      knowledge of all times of transitions from a given level of disability to the
      next level, but such data are often missing. We address methodological challenges
      due to partly missing transition times. To estimate the effects of prognostic
      factors on the risk of transitions between three consecutive disability levels,
      two methods were used to deal with missing data. Listwise deletion limited the
      analysis to subjects with complete data. Multiple imputation of missing data
      revealed that data were missing at random (MAR mechanism) and imputed the missing
      transition times from the Weibull model. The results were then compared with the
      full data set with the actual times established through chart review. Multiple
      imputation estimates were systematically closer to those from the full data set
      than the listwise deletion estimates.

PMID- 17215589
TI  - Structure and function of PICK1.
AB  - PICK1 is a peripheral membrane protein conserved from Caenorhabditis elegans to
      the human. It is expressed in many tissues with high levels in brain and testis.
      Inside cells, PICK1 is localized at the perinuclear region as well as specialized
      structures such as synapses of neurons. PICK1 contains a PDZ domain and a BAR
      domain. The PDZ domain of PICK1 binds to a large number of membrane proteins,
      especially proteins with C-terminal type II PDZ-binding motifs. The BAR domain of
      PICK1 binds to lipid molecules, mainly phosphoinositides. While the PDZ domain
      and the linker region of PICK1 enhance BAR domain's lipid binding, the C-terminal
      region of PICK1 inhibits its lipid binding. PICK1 regulates the subcellular
      localization and surface expression of its PDZ-binding partners. Lipid binding of
      PICK1's BAR domain is important for this regulation. With its PDZ domain
      interacting with membrane proteins and its BAR domain binding to lipids, the
      unique structure of PICK1 enables it to couple membrane proteins to protein
      trafficking machinery.

PMID- 17215592
TI  - The grammar of the psychiatric interview. A plea for the second-person mode of
      understanding.

PMID- 17215593
TI  - Existence and pluralism: the rediscovery of Karl Jaspers.
AB  - Karl Jaspers has been recognized in psychiatry mostly for his influence on
      phenomenology and on certain aspects of psychopathology, such as our
      understanding of delusions. In this paper, I will highlight the need to
      rediscover Jaspers' work in terms of other important ideas that he can contribute
      to psychiatry, in particular the concepts of limit situations, transcendence and
      pluralism. Limit situations refer to the fact that human life is characterized by
      existential situations, or crises, which become opportunities for authentic
      existence. Transcendence refers to the notion that freedom is an important aspect
      of human existence and cannot be explained by purely scientific understanding or
      encompassed by any purely rationalistic system of thought. Pluralism is perhaps
      Jaspers' most original perspective, which has still failed to be adequately
      appreciated by the psychiatric profession. The idea here is that science means
      understanding the methods by which we obtain knowledge, along with the
      presuppositions and limits of those methods. Contemporary psychiatry has only a
      limited appreciation of Jaspers' work. In this paper, I attempt to describe these
      important concepts that can help us understand what we do in psychiatry, what we
      should be doing and why.

PMID- 17215594
TI  - Lifelong course of positive and negative symptoms in chronically
      institutionalized patients with schizophrenia.
AB  - BACKGROUND: Despite widespread policies of deinstitutionalization, a substantial
      number of patients with schizophrenia require continuous custodial care. The
      hospital records of such patients provide contemporaneous documentation of
      symptoms throughout the illness, permitting a longitudinal study of the course of
      symptoms. We sought to describe this course, and to determine the influences of
      sex, age of onset, and treatment on its evolution. METHODS: Using the modified
      Diagnostic Evaluation After Death, we performed standardized chart reviews of 99
      chronic inpatients who remained in state institutions through the 1960's and
      1970's and subsequently died in those institutions. Data were available from the
      onset of illness until death. RESULTS: We found significant decreases in positive
      symptoms and increases in negative symptoms over the course of the illness.
      Symptom patterns were analyzed by repeated measures ANOVA. Onset before age 25
      was associated with greater numbers of negative symptoms at a given age (p =
      0.05). Female sex was associated with greater numbers of positive symptoms
      (p=0.04). The widespread introduction of neuroleptic drugs in the mid-1950's did
      not affect the trends in symptom patterns. CONCLUSIONS: The lifetime course of
      schizophrenia in chronically institutionalized individuals is characterized by a
      decrease in positive symptoms and an increase in negative symptoms. Schizophrenia
      with earlier onset is associated with greater numbers of negative symptoms
      throughout life. In this sample of patients, chronically hospitalized until
      death, neuroleptic drugs failed to effect a persistent decrease in positive
      symptoms.

PMID- 17215595
TI  - IREL - A psychometric instrument for measuring life themes.
AB  - BACKGROUND: Although biographical narratives and work involving the meaning of
      biographical episodes is a central focus in any psychotherapy, there remains a
      lack of psychometric instruments for measuring the autobiographical construction
      as such. We will be presenting a theoretical model of an autobiographical
      construction of life themes and the Interview of Retrospective Exploration of
      Life themes (IREL) will be used as the basis of a psychometric instrument. The
      IREL takes about 90-120 min. The interrater reliability and test-retest
      reliability will be examined. METHODS: Two samples of 21 and 23 mentally healthy
      subjects were recruited. In addition to the IREL, the Beck Depression Inventory
      (BDI) and SCID were also used to control for psychopathological status and
      depressive mood. RESULTS: According to our data, biographical events can be
      explored objectively and reliably using the IREL. Minor test-retest variability
      of the affective valence of life themes is not state-dependent. CONCLUSIONS:
      Setting aside limitations due to the small sample sizes, the results suggest that
      the proposed interview is an objective and reliable instrument for measuring
      central issues within the subjective biographical construction (life themes).

PMID- 17215590
TI  - Depression of glutamate and GABA release by presynaptic GABAB receptors in the
      entorhinal cortex in normal and chronically epileptic rats.
AB  - Presynaptic GABA(B) receptors (GABA(B)R) control glutamate and GABA release at
      many synapses in the nervous system. In the present study we used whole-cell
      patch-clamp recordings of spontaneous excitatory and inhibitory synaptic currents
      in the presence of TTX to monitor glutamate and GABA release from synapses in
      layer II and V of the rat entorhinal cortex (EC)in vitro. In both layers the
      release of both transmitters was reduced by application of GABA(B)R agonists.
      Quantitatively, the depression of GABA release in layer II and layer V, and of
      glutamate release in layer V was similar, but glutamate release in layer II was
      depressed to a greater extent. The data suggest that the same GABA(B)R may be
      present on both GABA and glutamate terminals in the EC, but that the
      heteroreceptor may show a greater level of expression in layer II. Studies with
      GABA(B)R antagonists suggested that neither the auto- nor the heteroreceptor was
      consistently tonically activated by ambient GABA in the presence of TTX. Studies
      in EC slices from rats made chronically epileptic using a pilocarpine model of
      temporal lobe epilepsy revealed a reduced effectiveness of both auto- and
      heteroreceptor function in both layers. This could suggest that enhanced
      glutamate and GABA release in the EC may be associated with the development of
      the epileptic condition.

PMID- 17215596
TI  - Obsession in the strict sense: A helpful psychopathological phenomenon in the
      differential diagnosis between obsessive-compulsive disorder and schizophrenia.
AB  - The paper presented follows the hypothesis that differentiation between obsessive
      compulsive disorder and schizophrenia is possible only by focusing on the single
      phenomenon of obsession. The statement of a nosological specificity of obsession,
      called obsession in the strict sense, is set against the current views of ICD-10
      and DSM-IV of obsession as a ubiquitous, non-specific phenomenon appearing in
      comorbidities. In the succession of the paper, the historical development of
      these two very different views and their clinically mixing is reconstructed. The
      phenomenological clarification of the structure of the obsessive phenomena leads
      to the term of obsession in the strict sense. The distinction between obsessive
      compulsive disorder and schizophrenia can take place at the psychopathological
      interface between obsession in the strict sense and delusional idea. The
      examination of the literature on the connection between obsessive-compulsive
      disorder and schizophrenia shows that there is no definitive connection between
      obsession in the strict sense and schizophrenia. Finally, some case reports are
      presented to sharpen clinical suspicion for other possibly wrong diagnoses.

PMID- 17215597
TI  - Discriminant ability and criterion validity of the HoNOS in Italian psychiatric
      residential facilities.
AB  - BACKGROUND: The Health of the Nation Outcomes Scales (HoNOS) was developed as an
      inclusive and comprehensive instrument to assess patient outcomes in 4 main
      domains: behaviour, cognitive and physical impairment, symptoms and social
      functioning/context. Concerns about the reliability and validity of the HoNOS
      have been raised. The aim of this study was to further investigate the
      discriminatory ability of the HoNOS; criterion validity was also examined.
      SAMPLING AND METHODS: A broad sample of patients with psychotic disorders,
      admitted to 265 Italian residential facilities, were rated by trained research
      assistants and local staff on the HoNOS, Global Assessment of Functioning, Life
      Skills Profile, and Physical Health Index. Discriminant function analysis was
      used to examine the ability of the HoNOS items to correctly classify patients
      with positive symptoms, substantial psychosocial impairment or physical
      disability. The HoNOS criterion validity was also examined. RESULTS: On the
      whole, the pattern of correlations between the HoNOS and the other corresponding
      measures was consistent. However, the majority of the correlations were only
      moderate. In discriminant function analysis, the classification procedure
      correctly classified 55.7% of the patients. CONCLUSIONS: Although the HoNOS has
      many advantages in its brevity, it may lack sufficient discriminatory ability for
      certain patient groups. Further, it correlates only moderately with measures of
      disability and physical health status. These findings suggest that the HoNOS
      alone might be insufficient for routine evaluation and should probably be
      supplemented by additional measures.

PMID- 17215598
TI  - A Psychometric evaluation of the German version of the 'Health of the Nation
      Outcome Scales, HoNOS-D': on the feasibility and reliability of clinician
      performed measurements of severity in patients with mental disorders.
AB  - BACKGROUND: The assessment of the severity of a mental illness is a central
      component in the treatment of patients with mental disorders in both the in- and
      outpatient settings. In Great Britain, the 'Health of the Nation Outcome Scales,
      HoNOS' were developed to assess the health and social functioning of patients
      with mental disorders. AIMS: To examine the psychometric properties, especially
      the feasibility and reliability, of a German version of the HoNOS (HoNOS-D) and
      to thus provide international data for the comparison of different mental health
      services. SAMPLING AND METHODS: The HoNOS was translated into German (HoNOS-D) in
      an extensive and multilayered consensus procedure. The HoNOS-D was then reviewed
      within the framework of a pilot study on quality assurance measures implemented
      by the German statutory health insurance institutes in 11 hospitals. Assessments
      were made of the psychometric qualities of feasibility and reliability using a
      representative sample of patients with mental and behavioral disorders. RESULTS:
      An analysis of the feasibility of the HoNOS-D showed a range of missing values
      between 1.3 and 4.5% for 11 of the 12 items. An item analysis showed that three
      items of the HoNOS-D are particularly positively skewed. In most instances, the
      individual items of the rating scale exhibited only slight correlations to each
      other. With regard to retest reliability, satisfactory intraclass correlations
      between 0.80 and 0.91 were seen for 9 of the 12 items. CONCLUSIONS: The authors
      of the original version of the HoNOS [Wing et al.:Br J Psychiatry 1998;172:11-18]
      primarily emphasized the feasibility of the instrument and the independence of
      the individual items and dimensions. The analysis of the missing values showed
      satisfactory results for feasibility. The intercorrelation matrix of the
      individual items also exhibited only few correlations >0.30. The retest
      reliability also proves to be satisfactory for the majority of the items. The
      narrow distribution of some of the items must be critically discussed in
      comparison to analyses of results in other countries (e.g. Great Britain) and
      other settings (e.g. inpatient psychiatric hospitals or outpatient
      psychotherapy).

PMID- 17215599
TI  - Psychometric properties of the Borderline Symptom List (BSL).
AB  - BACKGROUND: The Borderline Symptom List (BSL) was developed as a self-rating
      instrument to specifically quantify borderline-typical symptomatology. The items
      are based on the criteria of the DSM-IV, the Diagnostic Interview for Borderline
      Personality Disorder - revised version, the opinions of clinical experts and
      borderline patients. The psychometric properties and validity of the BSL have
      been investigated in several studies. SAMPLING AND METHODS: A total of 380
      borderline patients and 204 healthy controls scored the items. A factor analysis
      of the BSL items suggests the following subscales: 'self-perception', 'affect
      regulation', 'self-destruction', 'dysphoria', 'loneliness', 'intrusions' and
      'hostility'. RESULTS: The internal reliability as well as the test-retest
      reliability within 1 week are high. Different aspects of validity (e.g.
      comparison between groups) provide favorable results. Pre-post comparisons after
      3 months of dialectical behavioral treatment reveal a significant reduction of
      the total score and of 5 of the 7 subscales. CONCLUSIONS: This indicates that the
      BSL is sensitive to therapeutically induced change of borderline-typical
      impairment.

PMID- 17215600
TI  - The measurement of fatigue in depression.

PMID- 17215601
TI  - Measurement issues across different cultures.
AB  - PURPOSE: The purposes of this methodologic paper are to (1) describe theoretical
      background in conducting research across different cultures; (2) address
      measurement issues related to instrument administration; and (3) provide
      strategies to deal with measurement issues. METHODS: A thorough review of the
      literature was conducted. A theoretical background is provided, and examples of
      administering instrument in studies are described. RESULTS: When applying an
      instrument to different cultures, both equivalence and bias need to be
      established. Three levels of equivalence, i.e., construct equivalence,
      measurement unit equivalence, and full score comparability, need to be explained
      to maintain the same concept being measured. In this paper, sources of bias in
      construct, method, and item are discussed. Issues related to instrument
      administration in a cross-cultural study are described. CONCLUSION: Researchers
      need to acknowledge various group differences in concept and/or language that
      include a specific set of symbols and norms. There is a need to question the
      philosophical and conceptual appropriateness of an assessment measure that has
      been conceptualized and operationalized in a different culture. Additionally,
      testing different response formats such as narrowing response range can be
      considered to reduce bias.

PMID- 17215602
TI  - Effects of programmed information on coping behavior and emotions of mothers of
      young children undergoing IV procedures.
AB  - PURPOSE: To determine the effects of provision of information on mother's problem
      focused coping ability during their child's intravenous procedure. METHODS: Data
      were collected from 56 mothers whose children have admitted to pediatric ward in
      the hospital. The participants included 27 intervention group mothers and 29
      control group mothers. For the information intervention, "Programmed Information
      for Parental Coping before Intravenous Procedure (PIPC-IP)", video program was
      made based on self-regulation theory for the experimental group mothers. Mother's
      coping ability was measured by parental supportive behavior, parental beliefs and
      Profile of Mood State (POMS). RESULTS: Mothers who received PIPC-IP showed
      significantly higher levels of supportive behavior (t = 3.55, p = .005) and
      Parental Beliefs (t = 2.95, p = .005), but no significant difference in negative
      mood on POMS (t = .15, p = .87) compared to mothers in the control group.
      CONCLUSIONS: These results demonstrate that PIPC-IP is an effective intervention
      to increase the supportive behaviors and beliefs of mothers' problem focused
      coping ability but not the negative mood.

PMID- 17215603
TI  - Development and evaluation of a PBL-based continuing education for clinical
      nurses: a pilot study.
AB  - PURPOSE: The purposes of this study were to develop a PBL program for continuing
      nurse education and to evaluate the program after its implementation. METHODS:
      The PBL program was developed in the core cardio-pulmonary nursing concepts
      through a collaborative approach with a nursing school and a hospital. The PBL
      packages with simulation on ACLS were implemented to 40 clinical nurses. The
      entire PBL program consisted of six 3-hour weekly classes and was evaluated by
      the participants' subjective responses. RESULTS: Two PBL packages in cardio
      pulmonary system including clinical cases and tutorial guidelines were developed.
      The 57.5% of the participants responded positively about the use of PBL as
      continuing nurse education in terms of self-motivated and cooperative learning,
      whereas 20.0% of the participants answered that the PBL method was not suitable
      for clinical nurses. Some modifications were suggested in grouping participants
      and program contents for PBL. CONCLUSION: The PBL method could be utilized to
      promote nurses' clinical competencies as well as self-learning abilities. Further
      research is needed in the implementation strategies of PBL-based continuing
      education in order to improve its effectiveness.

PMID- 17215604
TI  - Discriminative factor analysis of juvenile delinquency in South Korea.
AB  - PURPOSE: The present study was intended to compare difference in research
      variables between delinquent adolescents and student adolescents, and to analyze
      discriminative factors of delinquent behaviors among Korean adolescents. METHODS:
      The research design of this study was a questionnaire survey. Questionnaires were
      administered to 2,167 adolescents (1,196 students and 971 delinquents), sampled
      from 8 middle and high school and 6 juvenile corrective institutions, using the
      proportional stratified random sampling method. Statistical methods employed were
      Chi-square, t-test, and logistic regression analysis. RESULTS: The discriminative
      factors of delinquent behaviors were smoking, alcohol use, other drug use, being
      sexually abused, viewing time of media violence and pornography. Among these
      discriminative factors, the factor most strongly associated with delinquency was
      smoking (odds ratio: 32.32). That is, smoking adolescent has a 32-fold higher
      possibility of becoming a delinquent adolescent than a non-smoking adolescent.
      CONCLUSIONS: Our findings, that smoking was the strongest discriminative factor
      of delinquent behavior, suggest that educational strategies to prevent adolescent
      smoking may reduce the rate of juvenile delinquency. Antismoking educational
      efforts are therefore urgently needed in South Korea.

PMID- 17215605
TI  - Development and evaluation of the Web-based wound care course for undergraduate
      nursing students.
AB  - PURPOSE: This study developed a web-based wound care course for undergraduate
      nursing students and evaluated the course's content, system, and student
      satisfaction. METHODS: This study was done in three stages, the development of
      the web-based wound care course, the implementation and evaluation of the course.
      The course was developed based on the ARCS model. 80 undergraduate nursing
      students to Y University in Korea used the web-based wound care program during
      four weeks. After that, they completed questionnaires, evaluating the contents,
      system, and their satisfaction. RESULTS: Eighteen learning objectives were used
      to create the web-based wound care course and the course was developed with 7
      chapters and 20 subsections. The analysis of the questionnaires showed a mean
      score for content and system-related items of 3.04 each, out of a possible 4
      points. Student satisfaction items had a mean score of 2.89. CONCLUSIONS: The web
      based course allowed students access to the course anytime and anywhere, and
      according to their own learning abilities. However this advantage would only be
      possible when nurse educators develop qualitative web-based course to meet the
      demand of a complex health care system as well as the needs of the students and
      the effectively incorporate it into traditional lectures.

PMID- 17215606
TI  - The effects of infant massage on weight, height, and mother-infant interaction.
AB  - PURPOSE: The purpose of this study was to test the effects of infant massage
      (auditory (mother's voice), tactile/kinesthetic (massage) and visual (eye to eye
      contact) stimulation) on weight and height of infant and mother-infant
      interaction with normal infants over a period of 4 weeks. METHOD: This study was
      designed as a nonequivalent control group pretest-posttest design. The
      experimental group infants (aged 2-6 months) participated in one of the infant
      massage programs at the health district center for 4 weeks. The control group
      (N=26) was paired with the experimental group (N=26) by matching the infant's age
      and sex. Infant weight, height, and mother-infant interaction were measured two
      times and recordings of the mother-infant interaction were done using the video
      equipment in a room at the health center for 10 minutes. RESULTS: After 4 weeks
      of massage, there were no significant differences weight gain and height increase
      between the two groups. Comparison of the total scores for the mother-infant
      interaction between the two groups showed a significant difference (t=5.21,
      p=.000). There were also significant differences on maternal response (t=3.78,
      p=000), infant response (t=5.71, p=000) and dyadic response (t=4.05, p=000) in
      the mother-infant interaction between the two groups. CONCLUSION: Overall, the
      results of this study reassure that infant massage facilitates the mother-infant
      interaction for infants and mothers who give massage to their baby.

PMID- 17215607
TI  - The roles of critical care advanced practice nurse.
AB  - PURPOSE: To determine and compare the perception among nurses and doctors of the
      roles and tasks of critical care advanced practice nurses (APNs) in order to
      establish standardized and formally agreed role criteria for such critical care
      APNs. METHOD: This study measured and analyzed the necessity of each of the roles
      and tasks of critical care APNs, as perceived by nurses and doctors, through a
      survey of 121 participants: 71 nurses in 7 intensive care units (ICUs) at a
      general hospital in Seoul, and 50 doctors who used ICUs. Data collection utilized
      a questionnaire of 128 questions in the following fields: direct practice (79),
      leadership and change agent (17), consultation and collaboration (15), education
      and counseling (11), and research (6). RESULTS: Both the nurses' and the doctors'
      groups confirmed the necessity of critical care APNs, with doctors who frequently
      used ICUs indicating a particularly strong need. As for the priority of each role
      of critical care APNs, the nurses considered direct practice to be the most
      critical, followed by education and counseling, research, consultation and
      collaboration, and leadership and change agent. The doctors also considered
      direct practice to be the most critical, followed by education and counseling,
      consultation and collaboration, research, and leadership and change agent. There
      was a statistically significant difference between how the two groups regarded
      all the roles, except for the consultation and collaboration roles. As for the
      necessity of each role of critical care APNs, the nurses considered research to
      be the most necessary, followed by education and counseling, consultation and
      collaboration, leadership and change agent, and direct practice. The doctors, on
      the other hand, considered education and counseling to be the most necessary,
      followed by research, consultation and collaboration, leadership and change
      agent, and direct practice. The responses of the two groups to all the roles,
      except for education and counseling roles, were significantly different.
      CONCLUSION: Nurses and doctors have different perceptions of the roles and tasks
      of critical care APNs. Thus, it is necessary for the combined nursing and medical
      fields to reach an official agreement on a set of criteria to standardize for the
      roles and tasks of critical care APNs.

PMID- 17215608
TI  - The effects of brisk walking versus brisk walking plus diet on triglycerides and
      apolipoprotein B levels in middle-aged overweight/obese women with high
      triglyceride levels.
AB  - PURPOSE: The purpose of this study were to investigate the effects of a 12-week
      brisk walking program on triglycerides (TG) and apolipoprotein B (Apo B) and to
      compare these effects to those of a brisk walking plus diet program in middle
      aged overweight/obese (BMI> or =23) Korean women with hypertriglyceridemia.
      METHOD: This analysis was done with nineteen middle-aged overweight/obese Korean
      women who completed either the brisk walking program (9 women) or the brisk
      walking plus diet program (10 women) for 12 weeks. The brisk walking consisted of
      walking for 20 to 50 minutes/day at an intensity of 40 to 70% of heart rate
      reserve (HRR) for 3 to 6 days/week. The diet consisted of 60 minutes of group
      education and 20 to 30 minutes of individual counseling every week. TG and Apo B
      were assessed pre- and post-intervention. RESULTS: TG and Apo B decreased
      significantly after the brisk walking program (Z = -2.31, p = 0.021; Z = -2.59, p
      = 0.009). TG and Apo B lowering effects of the brisk walking program were not
      significantly different from those of the brisk walking plus diet program (U =
      37.0, p = 0.549; U = 42.0, p = 0.842). CONCLUSION: Brisk walking can be an
      effective intervention for overweight/obese middle-aged women with
      hypertriglyceridemia in reducing cardiovascular risk by lowering TG and Apo B
      levels. Adding diet to brisk walking may have no additional significant effects
      on changes in TG and Apo B.

PMID- 17215609
TI  - Effects of the weight management program based self-efficacy for body
      composition, blood lipid profile, weight self-efficacy lifestyles, depression in
      middle-aged obese women.
AB  - PURPOSE: This study was done to determine the effects of weight management
      program using self-efficacy in middle-aged obese women. The study also attempted
      to measure the effects of the program on the weight efficacy lifestyle, body
      composition, and depression. METHOD: The research design of this study was a
      nonequivalent control group pretest-posttest design. The experimental group
      consisted of 21 middle-aged obese women and another 21 middle-aged obese women in
      the control group. The women in the experimental group participated in the weight
      management program for 12 weeks using self-efficacy. The weight management
      program using self-efficacy included education on effects of exercise for weight
      control, aerobic exercise program, muscle training and counseling through the
      telephone. RESULTS: After 12 weeks of participation in the program, BMI
      (p<.0001), body fat % (p<.0001), abdominal fat (p<.0001), in the experimental
      group were significantly decreased compared to the control group. Weight self
      efficacy lifestyle (p<.0001) and depression (p=.006) in the experimental group
      were significantly improved after the program compared to the control group.
      According to these findings, weight management program self-efficacy for middle
      aged obese women could increase weight efficacy lifestyle, and decrease
      depression, BMI, body fat, and abdominal fat. CONCLUSION: The result also
      suggested that the increasing weight efficacy and lifestyle help the obese women
      to perform and continue exercise. This program could be used in the community
      such as public health center for weight care and mental health promotion of
      middle-aged obese women.

PMID- 17215610
TI  - Effects of a bereavement intervention program on depression and life satisfaction
      in middle aged widows in Korea.
AB  - PURPOSE: This study was designed to examine the effects of a bereavement
      intervention program on levels of depression and life satisfaction in middle aged
      widows in Korea. METHODS: A quasi-experimental design with non-equivalent control
      group pretest-posttest was used. The subjects (control group, n = 10;
      intervention group, n = 17) were bereaved less than 6 months in G City and J
      Province, Korea. The bereavement intervention program consisted of Dan-jeon
      breathing, self-help group activities and a health examination. The experimental
      group attended 10 sessions of a bereavement intervention program. The control
      group had a health examination without the intervention program. For both groups,
      the level of depression and life satisfaction levels were measured before and
      after the experiment. RESULTS: The decrement of depression level in the
      experimental group was significantly greater than in the control group (p<.001).
      The increment in life satisfaction in the experimental group was significantly
      greater than in the control group (p<.001). CONCLUSION: The results suggested
      that the bereavement intervention program was effective in decreasing level of
      depression and in increasing the life satisfaction of widows. Accordingly, a
      bereavement intervention program can be applied as an intervention to help
      widows.

PMID- 17215613
TI  - Squamous cell carcinoma in situ: a historical note.

PMID- 17215611
TI  - Pelvic floor muscle exercise by biofeedback and electrical stimulation to
      reinforce the pelvic floor muscle after normal delivery.
AB  - PURPOSE: This study was conducted to investigate the effectiveness of pelvic
      floor muscle exercise using biofeedback and electrical stimulation after normal
      delivery. METHODS: The subjects of this study were 49 (experimental group: 25,
      control group: 24) postpartum women who passed 6 weeks after normal delivery
      without complication of pregnancy, delivery and postpartum. The experimental
      group was applied to the pelvic muscle enforcement program by biofeedback and
      electrical stimulation for 30 minutes per session, twice a week for 6 weeks,
      after then self-exercise of pelvic floor muscle was done 50-60 repetition per
      session, 3 times a day for 6 weeks. Maximum pressure of pelvic floor muscle
      contraction (MPPFMC), average pressure of pelvic floor muscle contraction
      (APPFMC), duration time of pelvic floor muscle contraction (DTPFMC) and the
      subjective lower urinary symptoms were measured by digital perineometer and
      Bristol Female Urinary Symptom Questionnaire and compared between two groups
      prior to trial, at the end of treatment and 6 weeks after treatment. RESULTS: The
      results of this study indicated that MPPFMC, APPFMC, DTPFMC were significantly
      increased and subjective lower urinary symptoms were significantly decreased
      after treatment in the experimental group than in the control group. CONCLUSIONS:
      This study suggested that the pelvic floor muscle exercise using biofeedback and
      electrical stimulation might be a safer and more effective program for
      reinforcing pelvic floor muscle after normal delivery.

PMID- 17215614
TI  - Onychomycosis: a 3-year clinicomycologic hospital-based study.
AB  - BACKGROUND: Despite onychomycosis being an established entity, only a few studies
      are available from the Indian subcontinent. The authors investigated the
      comprehensive pattern of the condition. AIM: To investigate the epidemiologic,
      clinical, and mycologic factors associated with onychomycosis in 50 patients
      using a prospective study design. METHODS: Fifty patients with potassium
      hydroxide-positive tests were evaluated according to a predetermined protocal
      recording details of epidemiologic, clinical, and mycologic characteristics. The
      collected data were analyzed to determine the correlation of various parameters.
      RESULTS: Distal and lateral subungual onychomycosis, total dystrophic
      onychomycosis, and superficial white onychomycosis variants of onychomycosis were
      identified, mostly in men 21-30 years of age (mean age, 34.5 years).
      Epidemiologic characteristics were instrumental to either initiate, perpetuate,
      or disseminate the disease process. Trichophyton rubrum and Trichophyton
      mentagrophytes were the main causative dermatophytes; yeasts and molds were less
      common. CONCLUSIONS: Recognition of onychomycosis is less difficult providing the
      clinician is aware of the entity. Should the etiologic diagnosis be made, its
      eradication is desirable to surmount its implication in the society at large.

PMID- 17215615
TI  - AIDS in pregnancy, part I: epidemiology, testing, effect on disease progression,
      opportunistic infections, and risk of vertical transmission.
AB  - Contribution of acquired immunodeficiency syndrome/human immunodeficiency virus
      (HIV) infection to pregnancy mortality rates is difficult to estimate; however,
      it appears to be one of the leading causes of death, at least in developing
      countries. Prenatal HIV testing affords the best opportunity for the prevention
      of perinatal HIV transmission. Rapid HIV testing substantially increases the
      proportion of women who obtain HIV results compared with conventional enzyme
      linked immunosorbent assay testing, thus maximizing perinatal HIV interventions.
      Pregnancy appears to have no effect on the course of HIV disease. Infections due
      to a variety of pathogens influence the clinical course of the HIV infection and
      may complicate pregnancy and increase maternal mortality. The main risk factors
      for mother-to-child HIV transmission are high maternal viral load and CD4 cell
      count <700 cells/mm3. The main protective factor is antiretroviral therapy.

PMID- 17215617
TI  - Verdeso (desonide) Foam, 0.05%.

PMID- 17215616
TI  - Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy: clinical aspects.
AB  - Nephrogenic systemic fibrosis, previously known as nephrogenic fibrosing
      dermopathy, is a novel fibrosing disorder characterized by prominent cutaneous
      and systemic fibrosis in patients with renal failure. Although initially
      descriptions of this disorder was described to be purely cutaneous, numerous
      subsequent reports have shown remarkable systemic involvement with fibrosis of
      numerous internal organs, including striated muscles, myocardium,
      microvasculature, lungs, and others, accompanied by elevation of systemic
      inflammation markers, such as erythrocyte sedimentation rate and C-reactive
      protein. The cutaneous manifestations are characterized by erythematous to browny
      skin induration with a peau d'orange appearance, plaques, nodules, and papules.
      Histopathologically, there is dermal and subdermal thickening with abundant
      collagen fibers and mucin deposits and a striking increase in the number of
      spindle-shaped fibroblastic cells. The disorder is clinically distinct from
      scleromyxedema, systemic sclerosis, and other cutaneous fibrosing syndromes. The
      cause is unknown, and currently there is no uniformly effective treatment.

PMID- 17215618
TI  - Silicone implants and connective tissue disease: 5 cases.

PMID- 17215619
TI  - Melasma.

PMID- 17215620
TI  - Laser and intense pulsed light for hair removal cannot cause virus inoculation-
      think again.

PMID- 17215621
TI  - Lamellar ichthyosis in a Saudi kindred.
AB  - A series of 20 patients aged 4-16 years presented with lamellar ichthyosis at the
      dermatology unit of King Faisal Hospital at Taif in western Saudi Arabia. Though
      they had come from different families, they all belonged to the same tribe that
      was confined to a rural area in the precincts of Taif. The tribe is known for
      consanguineous marriages. The affected children are from 5 sibships. All the
      children presented with generalized thick dark scales. The history revealed that
      they all were born with a thick membrane around them, which was shed soon after.
      Gradually over months and years there was development of generalized scaling. A
      prototype is shown in the Figure. The scales had become darker and thicker with
      the passage of time. There was no pruritus. Teeth and mucous membranes were
      normal. None of the patients had erythroderma. The associated findings in some of
      the children were ectropion and alopecia. Contractures including pseudoainhum
      were also observed in some children. None of the patients' parents was found to
      be affected with a similar condition. There was no improvement with age. Skin
      biopsies from several of the patients revealed only hyperkeratosis. All had to be
      managed with topical emollients since they could not afford oral retinoids.

PMID- 17215622
TI  - Sporotrichosis: success of itraconazole treatment.
AB  - An 82-year-old man with hypothyroidism presented with an ulcerated nodule on the
      dorsum of his left hand (Figure 1). The lesion had been present for about 3
      months. Similar lesions were present along the lymphatic distribution of the
      dorsum of his left forearm, proximal to the first lesion, as well as the dorsum
      of his right forearm. Laboratory findings were normal. Immune complexes,
      complement 3, and complement 4 were negative. A biopsy from an ulcerated nodule
      was taken for both histologic examination and culture. Hematoxylin and eosin
      sections showed a nonspecific chronic granulomatous reaction. No fungi were
      detected by periodic acid-Schiff stain and methenamine silver stain. Culture of
      tissue obtained from a skin biopsy of 1 lesion placed directly on Sabouraud agar
      produced colonies of Sporothrix schenckii (Figure 2). The diagnosis of
      lymphocutaneous sporotrichosis was confirmed.

PMID- 17215623
TI  - Subepidermal calcified nodule in a 7-month-old boy.
AB  - A 7-month-old healthy white boy presented for evaluation of a papule on his right
      ear. His mother reported a small cut-like lesion at this site shortly after birth
      that had gradually grown over time. The patient was born full term via repeat
      cesarean section. On physical examination, located on the right superior helix,
      there was a 5-6 mm, pink, firm papule with a rough scaly surface and peripheral
      erythema (Figure 1). The lesion was shave excised and sent for histologic
      analysis. Microscopic examination revealed a defect of the epidermis with
      underlying fibrin deposits (Figure 2). Subjacent to the ulcer, there was
      chondroid tissue, granulation tissue with prominent vascularity, and an extensive
      amount of amorphous calcified material throughout the dermis extending to the
      base of the specimen (Figure 3). The clinical and pathologic findings were
      consistent with a subepidermal calcified nodule (SCN), an uncommon idiopathic
      calcinosis. The lesion was surgically removed with good results.

PMID- 17215624
TI  - Dermatomyositis with panniculitis.
AB  - Case 1. A 23-year-old white housewife presented with an erythematous violaceous
      rash on her face, neck, chest, and limbs, particularly over the dorsum of the
      hands and fingers; diffuse alopecia; and an inability to climb stairs and get up
      from a low seat. The clinical examination showed red to violaceous well
      demarcated plaques on sun-exposed areas on the dorsum of the fingers and hands,
      with periungual erythema and telangiectasia; facial erythema; and heliotrope
      rash. There was also symmetric involvement of proximal muscles of the limbs.
      Laboratory examination showed hypergammaglobulinemia, elevated serum aspartate
      aminotransferase, and serum alanine aminotransferase; normal activities of
      creatinokinase, lactate dehydrogenase, and aldolase; an antinuclear antibody
      titer of 1:40 with a speckled pattern; negative anti-DNA and anti-Scl70; and
      normal serum complement levels (C3, C4, and CH50). Urinalysis results were within
      normal limits. Skin biopsy histopathology showed hyperkeratosis, edema of the
      upper epidermis, scattered inflammatory infiltrate, and focal accumulation of
      mucin in the form of acid mucopolysaccharides. Deep asymptomatic nodules on the
      inner upper limbs appeared later. Histopathology of these lesions showed focal
      areas of lobular panniculitis in the subcutaneous tissue, with lymphoplasmocytic
      inflammatory infiltrate without vasculitis (Figure 1 and Figure 2). Case 2. A 29
      year-old white housewife presented with an erythematous violaceous rash on her
      face, neck, chest, and lower extremities. Clinical examination showed red to
      violaceous well-demarcated aching plaques on the internal surface of the thighs
      and tips of the fingers; periungual erythema and digital petechiae; Raynaud's
      phenomenon; and bilateral ulnar and cervical enlarged lymph nodes. Laboratory
      examination showed elevated serum aspartate aminotransferase, alanine
      aminotransferase, creatinokinase, lactate dehydrogenase, and aldolase; negative
      venereal disease research test results; an antinuclear antibody titer of 1:1024
      with speckled pattern; negative anti-DNA and anti-Scl70; and normal serum
      complement levels (C3, C4, and CH50). Urinalysis results were within normal
      limits. Histopathology of the deep asymptomatic nodule on the inner left thigh
      showed lobular panniculitis with a scattered inflammatory infiltrate and diffuse
      fat necrosis, in addition to calcium deposition between the lipocytes and
      microcysts without vasculitis (Figure 3).

PMID- 17215625
TI  - Pros and cons of the pharmaceutical industry and education.

PMID- 17215626
TI  - Intensive statin treatment or combination therapy in high-risk patients.

PMID- 17215627
TI  - A new approach for low-cost noninvasive detection of asymptomatic heart disease
      at rest.
AB  - It would be useful to have an inexpensive, noninvasive point-of-care test for
      early detection of asymptomatic heart disease. This study used impedance
      cardiography (ICG) in a new way to assess heart function that did not use stroke
      volume or cardiac output. There is a model of the ICG dZ/dt waveform that may be
      used as a template to represent normal heart function. The hypothesis was that a
      dZ/dt waveform which deviates from that template should indicate heart
      dysfunction and therefore heart disease. The objective was to assess the accuracy
      of this new ICG approach, using echocardiography as the standard. Thirty-four
      outpatients undergoing echocardiographic testing were tested by ICG while sitting
      upright and supine. All patients had no symptoms or history of a structural or
      functional heart disorder. Echocardiographic testing showed 17 patients with
      abnormalities and 17 as normal. ICG testing yielded 16 true positives for heart
      dysfunction with 1 false negative (sensitivity = 94%) and 17 true negatives with
      no false positives (specificity = 100%). Considering that the cost, technical
      skill, and time required for this ICG test are comparable to those of an
      electrocardiograph, this new approach has potential as a point-of-care screening
      test for asymptomatic heart disease.

PMID- 17215628
TI  - Depressive symptoms and sex affect completion rates and clinical outcomes in
      cardiac rehabilitation.
AB  - Symptoms of depression are often seen in patients with coronary heart disease.
      Symptoms appear more commonly in women and are negatively associated with
      measures of cardiovascular health. Using multiple logistic regression analyses,
      the authors evaluated the independent effects of depression (as measured by the
      Beck Depression Inventory [BDI-II]) and sex on cardiac rehabilitation (CR)
      completion. In addition, in those who completed CR, the authors evaluated whether
      depressive symptoms and sex affected clinical outcomes. Women as well as
      participants with enrollment BDI-II scores > or =14 had significantly higher
      rates of CR noncompletion. Patients with BDI-II scores > or =14 who completed CR
      achieved significant improvements in lipid profile, body mass index, and exercise
      capacity regardless of sex. Women and individuals with BDI-II scores > or =14 are
      at risk for CR noncompletion and should be encouraged to complete CR, because
      cardiovascular benefits comparable to those seen in men and individuals with low
      BDI-II scores were achieved when these patients completed the CR program.

PMID- 17215629
TI  - Functional capacity after traditional Chinese medicine (qi gong) training in
      patients with chronic atrial fibrillation: a randomized controlled trial.
AB  - Evidence indicates that low energy expenditure protocols derived from traditional
      Chinese medicine may benefit patients with cardiac impairment; therefore, the
      authors carried out a randomized controlled trial to test a 16-week medically
      assisted qi gong training program for the physical rehabilitation of patients
      with stable chronic atrial fibrillation and preserved left ventricular function.
      Functional capacity variation was evaluated using the 6-minute walk test, which
      was performed at baseline, at the end of the intervention, and after 16 weeks.
      Thirty men and 13 women (mean age, 68+/-8 years) were randomized to the
      intervention protocol or to a wait-list control group. Qi gong training was well
      tolerated and, compared with baseline, trained patients walked an average 114
      meters more (27%) at the end of treatment (P<.001) and 57 meters more (13.7%) 16
      weeks later (P=.008). Control subjects showed no variation in functional
      capacity. These results seem promising and deserve confirmation with further
      research.

PMID- 17215630
TI  - High-density lipoprotein cholesterol: a potential therapeutic target for
      prevention of coronary artery disease.
AB  - High-density lipoprotein cholesterol has an important role in the pathophysiology
      of coronary artery disease. High-density lipoprotein cholesterol is becoming an
      increasingly important prognostic and therapeutic target. The purpose of this
      paper is to review the biochemical pathways involved in reverse cholesterol
      transport and to discuss potential, clinically based high-density lipoprotein
      therapies that may contribute to reduction in risk of atherosclerosis.

PMID- 17215631
TI  - Optimal treatment of dyslipidemia in high-risk patients: intensive statin
      treatment or combination therapy?
AB  - A recent update to the National Cholesterol Education Program's Adult Treatment
      Panel III guidelines suggests low-density lipoprotein cholesterol (LDL-C) goals
      of <70 mg/dL in very-high-risk patients and <100 mg/dL in high-risk patients.
      Currently available 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors
      (statins) are not equal in their ability to lower LDL-C, and it is unlikely that
      the substantial LDL-C reductions that are often needed in high-risk persons can
      be achieved with starting doses of some of the older statins. Possible
      alternatives in such cases include the use of high-dose statin therapy, a more
      efficacious statin, or combination therapy. Recent clinical data have
      demonstrated a greater likelihood of coronary heart disease event reduction with
      aggressive statin therapy that lowers LDL-C in a robust fashion (>30%-40%) than
      with moderate therapy. Until data from ongoing trials of combination therapy are
      available, however, monotherapy with a potent statin should be initiated to lower
      LDL-C. Nonetheless, for residual elevation in triglycerides and/or reduced high
      density lipoprotein cholesterol, adding a second agent (eg, fenofibrate, niacin)
      is a reasonable option.

PMID- 17215632
TI  - Clues to cardiovascular risk: an office-based approach.
AB  - Current tools for predicting coronary heart disease risk in the asymptomatic
      patient fall into 2 major categories: traditional population-based models and
      noninvasive imaging techniques. Population-based models that estimate
      cardiovascular risk are powerful clinical tools but do not utilize a large volume
      of patient-specific data that are readily available to the clinician and may help
      to identify at-risk patients. The use of high-technology noninvasive imaging has
      not been consistently validated and clinicians or patients often lack the
      resources for such testing. This paper reviews several commonly encountered
      historical, physical, radiologic, laboratory, and electrocardiographic markers of
      increased cardiovascular risk that may enhance clinicians' ability to identify
      individual patients at increased risk for coronary heart disease.

PMID- 17215633
TI  - Fitness: the ultimate marker for risk stratification and health outcomes?

PMID- 17215634
TI  - DREAM and SPARCL.

PMID- 17215635
TI  - Hepatitis C and statins: a future therapeutic avenue?

PMID- 17215636
TI  - Denial of standard treatment to the elderly: why?

PMID- 17215637
TI  - Usefulness of in-hospital change in B-type natriuretic peptide levels in
      predicting long-term outcome in elderly patients admitted for decompensated heart
      failure.
AB  - The usefulness of repeated measures of B-type natriuretic peptide (BNP) in
      elderly subjects with decompensated heart failure to improve risk stratification
      remains poorly known. This prospective cohort study included 61 consecutive
      patients older than 70 years (mean age, 82.7 years) hospitalized for
      decompensated heart failure. Clinical, radiologic, biologic, and echographic data
      were collected at admission and at discharge. The median BNP level at admission
      was 1136 pg/mL and the mean change during the hospitalization was -32%. Cardiac
      death or readmission were best predicted by the change in BNP levels, with the
      poorest prognosis in patients who did not achieve a decrease of at least 40%
      (hazard ratio, 4.03; 95% confidence interval, 1.50-10.84 in multivariate
      analysis). Admission of an elderly patient for decompensated heart failure is a
      daily situation in clinical practice, in which 2 BNP measurements seem to provide
      reliable information on long-term prognosis.

PMID- 17215638
TI  - Contemporary diagnosis and management of hypercholesterolemia in elderly acute
      myocardial infarction patients: a population-based study.
AB  - There are limited data regarding the diagnosis and treatment of
      hypercholesterolemia in elderly patients with acute myocardial infarction (AMI).
      The authors describe the in-hospital and discharge prescription patterns of lipid
      lowering agents in patients hospitalized with an AMI, and identify factors
      associated with low rates of utilization of these therapies. The authors analyzed
      the Minnesota Heart Survey, a population-based surveillance project that
      retrospectively abstracted the medical records of patients hospitalized with AMI
      in 2001-2002 from 21 hospitals in the Minneapolis-St Paul metropolitan area. They
      identified 2773 patients 30 years and older with an AMI. The mean total
      cholesterol was 175+/-45 mg/dL, the mean low-density lipoprotein cholesterol was
      104+/-38 mg/dL, and the mean high-density lipoprotein cholesterol was 44+/-14
      mg/dL. Statins were prescribed at discharge to 74.6%, 63.2%, and 38.5% of
      patients younger than 65, 65-74, and 75 years and older, respectively (P<.0001).
      The utilization of statins was highly correlated with the administration of other
      standard AMI therapies-aspirin, beta-blockers, angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers, and reperfusion therapy-and was more
      prevalent among patients undergoing percutaneous coronary intervention than among
      those undergoing coronary artery bypass surgery. Elderly patients remain less
      likely to receive lipid-lowering therapy following an AMI. Greater attention is
      required to ensure that elderly AMI patients without contraindications are
      appropriately treated with lipid-lowering therapy.

PMID- 17215639
TI  - Prevalence of comorbidities and their influence on blood pressure goal attainment
      in geriatric patients.
AB  - Hypertension in elderly patients is common and is associated with unique
      challenges. This study examines the prevalence of comorbidities in elderly
      hypertensive patients and evaluates the association between comorbidities and
      other covariates with blood pressure goal attainment. Data were collected through
      retrospective review of medical records and included patient characteristics,
      comorbidities, treatment-related variables, and blood pressure goal attainment.
      At least 1 comorbidity was present in 88% of patients, and 61% had multiple
      comorbidities. The most common comorbidity was isolated systolic hypertension.
      The presence of diabetes or isolated systolic hypertension at initial visit and
      treatment with a thiazide diuretic at the final clinic visit were associated with
      significantly higher odds of patients not achieving blood pressure goal. A
      diagnosis of heart failure was associated with lower odds of not achieving blood
      pressure goal. These issues should be given special consideration during the
      evaluation, treatment selection, and long-term monitoring of this population.

PMID- 17215640
TI  - The impact of exercise training on blood lipids in older adults.
AB  - Increasing physical activity is often prescribed to improve blood lipids;
      however, the efficacy of exercise in improving blood lipids in older adults is
      not clear. The objective of this study was to examine the effects of different
      exercise modes on blood lipid levels in previously sedentary older adults
      engaging in a 16-week exercise intervention. One hundred thirty-one subjects
      (mean age 74.6+/-6 years) were randomly assigned to a resistance training group,
      aerobic walking group, combined exercise group, or nonexercising control group.
      Blood lipids were measured at baseline, 8 weeks, and postintervention. Exercise
      mode did not impact blood lipids. All groups had lower lipid levels over time.
      Total cholesterol, low- and high-density lipoprotein, and triglycerides were
      significantly lower. The decrease in all groups, including the controls, may be
      due to a seasonal effect in older adults that has been documented in younger
      individuals.

PMID- 17215641
TI  - Aerobic and resistance exercise training in the elderly.

PMID- 17215642
TI  - Uncorrected tetralogy of Fallot in an 86-year-old patient.
AB  - This report describes the presentation and evaluation of an elderly man with
      uncorrected tetralogy of Fallot. The patient had remained fairly asymptomatic for
      much of his life. He presented to the hospital at age 86 with new-onset atrial
      fibrillation with rapid ventricular response and a non-ST-segment elevation
      myocardial infarction. Transthoracic and transesophageal echocardiography
      revealed infundibular pulmonic stenosis with a ventricular septal defect,
      overriding aorta, and right ventricular hypertrophy, findings consistent with
      unrepaired tetralogy of Fallot. Severe right ventricular pressure overload was
      also present. Coronary angiography revealed nonobstructive coronary artery
      disease. It was felt that the rapid atrial fibrillation resulted in right
      ventricular subendocardial ischemia that improved following restoration of sinus
      rhythm. After a systematic literature search, the authors believe this case
      represents the oldest reported patient with the diagnosis of uncorrected
      tetralogy of Fallot and serves as an example of a well-balanced congenital shunt.

PMID- 17215643
TI  - Informed consent.

PMID- 17215644
TI  - A 105-year-old heart.

PMID- 17215645
TI  - Surgery for asymptomatic mitral regurgitation in the elderly.

PMID- 17215646
TI  - Cardioverter-defibrillator implantation in an elderly patient with isolated
      ventricular noncompaction.

PMID- 17215647
TI  - Truly isorhythmic A-V dissociation.

PMID- 17215649
TI  - Clinical characteristics of resistant hypertension: the importance of compliance
      and the role of diagnostic evaluation in delineating pathogenesis.
AB  - Resistant hypertension is defined as failure to achieve goal blood pressure
      despite adherence to 3 different antihypertensive medications, one of which must
      be a diuretic. True resistant hypertension must be distinguished by apparent
      resistant hypertension, of which an important cause is medication nonadherence,
      which can be recognized through a variety of monitoring strategies and may be
      improved through better patient education. A thorough history and examination
      should focus on evaluating for associated factors such as medication and illicit
      drug use, alcoholism, obesity, and obstructive sleep apnea. Further evaluation to
      differentiate apparent resistant hypertension from true resistant hypertension
      should include consideration of ambulatory blood pressure monitoring to rule out
      white coat hypertension. Routine laboratory work will reveal chronic kidney
      disease, which is the most common associated factor in resistant hypertension.
      Secondary or identifiable causes of resistant hypertension include primary
      aldosteronism, renovascular disease, and pheochromocytoma. Diagnostic evaluation
      for identifiable causes should be tailored for each patient and guided by signs
      and symptoms, as well as risks and benefits.

PMID- 17215648
TI  - Resistant hypertension: prevalence and evolving concepts.
AB  - Resistant hypertension is a common medical disorder. Although the exact incidence
      of resistant hypertension is not established, estimates derived from recent
      outcome studies including the Antihypertensive and Lipid-Lowering Treatment to
      Prevent Heart Attack Trial (ALLHAT), Valsartan Antihypertensive Long-term Use
      Evaluation (VALUE), and Controlled Onset Verapamil Investigation of
      Cardiovascular End Points (CONVINCE) emphasize that this condition may be more
      common than previously thought. A major advance in our understanding of the
      pathogenesis and management of resistant hypertension is the recognition of the
      importance of aldosterone. Several investigators have postulated a direct role of
      aldosterone excess as an important mechanism for drug resistance in hypertension.
      The mechanisms whereby aldosterone elevates BP are complex. It was previously
      thought that aldosterone produced hypertension primarily by promoting sodium
      retention with consequent hypervolemia. Recent studies of the effects of
      aldosterone on vascular smooth muscle have, however, delineated several
      extrarenal mechanisms whereby aldosterone produces hypertension-primarily by its
      direct vasoconstrictor effects and by altering vascular compliance. Consequently,
      aldosterone blockade constitutes an effective intervention for treating resistant
      hypertension.

PMID- 17215650
TI  - Aldosterone and the vasculature: mechanisms mediating resistant hypertension.
AB  - The renin-angiotensin-aldosterone system appears to be one of the key factors in
      the development of hypertensive vascular disease. Identification of
      mineralocorticoid receptors in the heart, vasculature, and brain has raised
      speculation that aldosterone may directly mediate its detrimental effects in
      these target organs independent of angiotensin II. Aldosterone increases vascular
      tone due to endothelial dysfunction and enhances the pressor response to
      catecholamines and up-regulation of angiotensin II receptors. It induces
      electrolyte transport over the vascular smooth cell membrane and plays a crucial
      role in vascular remodeling of small and large arteries. Moreover, aldosterone is
      involved in vascular injury and promotes collagen synthesis, which leads to
      increased arterial stiffness and elevation of blood pressure. Aldosterone has
      also been shown to exert a number of effects in the central nervous system.
      Several human studies have shown that aldosterone is related to baroreflex
      resetting. Thus, in cases of severe hypertension, there would be fewer
      compensatory mechanisms to offset blood pressure elevation and ensuing vascular
      damage. Endothelial and vascular smooth muscle cells have the potential to
      synthesize aldosterone, and tissue aldosterone could play a more important role
      in resistant hypertension and target organ damage than circulating aldosterone.
      Understanding aldosterone synthase polymorphism may provide insight into blood
      pressure patterns and their consequences. Understanding the vascular mechanisms
      of aldosterone in resistant hypertension may explain why selective aldosterone
      receptor blockers might have beneficial effects in resistant hypertension.

PMID- 17215651
TI  - Low-dose aldosterone blockade as a new treatment paradigm for controlling
      resistant hypertension.
AB  - Treatment of resistant hypertension requires confirmation of true resistance,
      diagnosis and treatment of secondary causes of hypertension, adoption of
      appropriate lifestyle modifications, and effective use of multidrug
      antihypertensive regimens. Excessive volume retention often underlies resistant
      hypertension, so diuretics are generally necessary to achieve blood pressure (BP)
      goals. Although treatment regimens consisting of 3 or more agents have not been
      systematically evaluated, the author has found a triple regimen consisting of a
      thiazide diuretic, a calcium channel blocker, and an angiotensin-converting
      enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to be generally
      effective and well tolerated. Although hydrochlorothiazide is more widely used,
      chlorthalidone provides better BP reduction and should be preferentially used in
      patients with resistant hypertension, particularly if the patient remains
      uncontrolled on hydrochlorothiazide. Recent studies have demonstrated that low
      doses of aldosterone antagonists, when added to multidrug regimens that include a
      thiazide diuretic and an angiotensin-converting enzyme inhibitor or angiotensin
      receptor blocker, provide significant additional BP reduction, seemingly
      exceeding what would be expected with addition of alternative classes of agents.
      The degree of BP reduction induced by aldosterone blockade has been similar in
      patients with and without evidence of aldosterone excess. Aldosterone antagonists
      are generally safe and well tolerated. The most common adverse effect of low-dose
      spironolactone has been breast tenderness, occurring in about 10% of men.
      Hyperkalemia is uncommon, but can occur, necessitating biochemical monitoring.
      Risk of hyperkalemia is increased in patients with chronic kidney disease or
      diabetes, elderly patients, and patients already receiving an angiotensin
      converting enzyme inhibitor or angiotensin receptor blocker.

PMID- 17215652
TI  - Ambulatory blood pressure monitoring as an investigative tool for characterizing
      resistant hypertension and its rational treatment.
AB  - Ambulatory blood pressure (BP) monitoring has matured into a useful methodology
      that obtains automated measurements of brachial artery BP during a 24-hour
      period. Cardiovascular outcomes in the treated patient with hypertension are
      often better predicted by ambulatory BP than by office pressures. Consensus
      guidelines have advocated lower goals of treated office BP in the majority of
      patients with hypertension; guidelines for the goal of ambulatory BP are needed
      as well. Recently, prospective cohort studies have shown that individuals whose
      clinic pressure is relatively normal but whose 24-hour BP is elevated are more
      likely to have a cardiovascular event than individuals with both normal clinic BP
      and ambulatory BP. Along with the knowledge gained from analyses of higher-risk
      hypertension patients, recommendations can now be made for how to use ambulatory
      BP monitoring in clinical practice. For example, ambulatory BP monitoring may be
      useful in verifying 24-hour control in high-risk patients whose office BP appears
      to be normal at rest or during the peak effect time of their antihypertensive
      agents. Evidence is mounting from studies that support the use of ambulatory BP
      monitoring in patients with resistant hypertension at the time of diagnosis and
      following clinically guided therapy.

PMID- 17215653
TI  - Hypertension treatment guidelines: is it time for an update?

PMID- 17215654
TI  - Economic analysis of a randomized trial of academic detailing interventions to
      improve use of antihypertensive medications.
AB  - The authors estimated the costs and cost savings of implementing a program of
      mailed practice guidelines and single-visit individual and group academic
      detailing interventions in a randomized controlled trial to improve the use of
      antihypertensive medications. Analyses took the perspective of the payer. The
      total costs of the mailed guideline, group detailing, and individual detailing
      interventions were estimated at 1000 dollars, 5500 dollars, and 7200 dollars,
      respectively, corresponding to changes in the average daily per person drug costs
      of -0.0558 dollars (95% confidence interval, -0.1365 dollars to 0.0250 dollars)
      in the individual detailing intervention and -0.0001 dollars (95% confidence
      interval, -0.0803 dollars to 0.0801 dollars) in the group detailing intervention,
      compared with the mailed intervention. For all patients with incident
      hypertension in the individual detailing arm, the annual total drug cost savings
      were estimated at 21,711 dollars (95% confidence interval, 53,131 dollars savings
      to 9709 dollars cost increase). Information on costs of academic detailing could
      assist with health plan decision making in developing interventions to improve
      prescribing.

PMID- 17215655
TI  - Beneficial effects of angiotensin II type 1 receptor blocker antihypertensive
      treatment on inflammation indices: the effect of smoking.
AB  - The effect of long-term angiotensin II type 1 receptor blocker (ARB) therapy on
      inflammation indices has not been fully investigated in a hypertensive
      population. The authors evaluated 323 consecutive nondiabetic patients (mean age,
      57 years; 176 men; 92 smokers) with high renin activity and uncomplicated
      essential hypertension whose blood pressure levels normalized (from 163.9/100.7
      mm Hg to 131.6/82.8 mm Hg) after 4 weeks of ARB or ARB/diuretic treatment. All
      patients underwent full laboratory evaluation (routine examination of blood and
      urine, liver, kidney, thyroid function, and lipid and glucose profiles),
      including measurement of high-sensitivity C-reactive protein and serum amyloid A
      levels, at drug-free baseline, which was repeated after 6 months of ARB or
      ARB/diuretic treatment. A significant (P<.001) overall decrease was noted in both
      high-sensitivity C-reactive protein (-0.41+/-1.56 mg/dL) and serum amyloid A (
      0.62+/-2.03 mg/dL), but a smaller decrease in high-sensitivity C-reactive protein
      and serum amyloid A change was seen in the smoker subgroup compared with
      nonsmokers (P<.05), indicating that the ARB or ARB/diuretic anti-inflammatory
      effect may be adversely affected by smoking status.

PMID- 17215656
TI  - Prevalence, treatment, and control of hypertension in primary care: gaps, trends,
      and opportunities.
AB  - Since most cases of hypertension are managed in family practice, estimates of the
      prevalence, treatment, and control in the primary care population are needed to
      adequately address the burden of hypertension in Canada as it has in other
      countries. The authors used a large primary care research database to determine
      the prevalence of hypertension between 2000 and 2003. Blood pressure recordings
      were used to estimate the rates of prevalence, treatment, and control of
      hypertension for the overall population and for important subgroups. The
      prevalence of hypertension was 17.3%, most patients had untreated hypertension
      (68.6%), and only 15.8% had blood pressure treated and controlled. Higher rates
      of treatment and control were observed among older adults, those with type II
      diabetes, and those with a previous myocardial infarction. Odds of achieving
      target blood pressure were significantly better when combination therapy vs
      monotherapy was used. The prevalence of hypertension in primary care is high and
      most patients remain untreated; however, increased risk appears to lead to better
      treatment and control.

PMID- 17215658
TI  - Titration of HCTZ to 50 mg daily in individuals with stage 2 systolic
      hypertension pretreated with an angiotensin receptor blocker.
AB  - The authors studied the combination of hydrochlorothiazide (HCTZ) 50 mg/d plus
      olmesartan medoxomil (OM) 40 mg/d in stage 2 systolic hypertension during an
      extension phase of an open-label 12-week dose titration study. Subjects whose
      blood pressure remained above 120/80 mm Hg (n=105) on OM 40/HCTZ 25 mg/d
      subsequently received OM 40/HCTZ 50 mg/d for 4 weeks. Increasing HCTZ from 25
      mg/d to 50 mg/d decreased systolic blood pressure by 3.6 mm Hg, increased BP
      control rates (<140/90 mm Hg) from 70.4% to 77.5%, and increased BP normalization
      rates (<120/80 mm Hg) from 15.4% to 27.8%. The combination was well tolerated.
      Compared with OM 40 mg/d monotherapy, neither dose of HCTZ affected serum
      potassium, but both increased serum glucose by about 5%. There was a dose
      dependent increase in uric acid but no acute gout attacks. OM 40/HCTZ 50 mg/d is
      an effective strategy for managing stage 2 systolic hypertension.

PMID- 17215657
TI  - Efficacy and safety of treating stage 2 systolic hypertension with olmesartan and
      olmesartan/HCTZ: results of an open-label titration study.
AB  - This study investigated an aggressive treatment program for stage 2 systolic
      hypertension (pretreatment systolic blood pressure [SBP] > or = 160 mm Hg) using
      the angiotensin receptor blocker olmesartan medoxomil (OM) and
      hydrochlorothiazide (HCTZ). In this open-label, 16-week trial, 170 subjects
      received OM 20 mg/d for 3 weeks. If seated SBP/diastolic BP remained > or =
      120/80 mm Hg, subjects were advanced to successive 3-week courses of OM 40 mg/d,
      OM/HCTZ 40/12.5 mg/d, and OM/HCTZ 40/25 mg/d. OM 20 mg/d reduced mean SBP by 16.9
      mm Hg (P<.001), and there were further dose-dependent decreases in mean SBP to a
      maximum of 34.5 mm Hg with OM/HCTZ 40/25 mg/d. At study end, 75.1% of subjects
      achieved SBP goal (<140 mm Hg) and 16.0% achieved SBP normalization (<120 mm Hg).
      Treatment was well tolerated at all doses. The addition of HCTZ did not change
      serum potassium levels but resulted in a dose-independent but not symptomatic
      increase in serum glucose and uric acid. The authors conclude that an OM-based
      regimen, with or without HCTZ in conventional doses, is effective in controlling
      and normalizing BP in stage 2 systolic hypertension.

PMID- 17215659
TI  - Reduction of stroke risk factors.
AB  - In October 2006, a panel of experts participated in a teleconference to discuss
      the reduction of stroke risk factors in patients at risk for stroke. The panel
      was chaired by John B. Kostis, MD, Professor and Chairman, Department of Medicine
      at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson
      Medical School, New Brunswick, NJ. Also participating were Philip B. Gorelick,
      MD, MPH, Director, Center for Stroke Research, University of Illinois College of
      Medicine, Chicago, IL, and Franz H. Messerli, MD, St Luke's-Roosevelt Hospital
      Center, New York, NY.

PMID- 17215660
TI  - Do angiotensin receptor antagonists decrease hsCRP independent of blood pressure 
      and does it matter?

PMID- 17215661
TI  - Hypertension associated with rhabdomyolysis.
AB  - Primary aldosteronism accompanied by hypokalemia is a cause of secondary
      hypertension. Diagnosis of primary aldosteronism has increased dramatically in
      recent years with the wider availability of aldosterone and plasma renin activity
      measurements. The authors present the case of a patient with resistant
      hypertension and severe hypokalemia that evaded diagnosis until complications
      from hypokalemia occurred.

PMID- 17215662
TI  - Neurovascular compression of the medulla: can it cause neurogenic hypertension?

PMID- 17215663
TI  - Hypertensive emergency with cardiac tamponade associated with hypothyroidism.

PMID- 17215664
TI  - Combination ACE inhibitor and angiotensin receptor blocker therapy - future
      considerations.
AB  - Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are
      regularly prescribed for the management of hypertension. Each of these drug
      classes has also been shown to provide survival benefits for patients with heart
      failure, proteinuric chronic kidney disease, and/or a high cardiac risk profile.
      The individual gains seen with each of these drug classes have led to speculation
      that their combination might offer additive if not synergistic outcome benefits.
      The foundation of this hypothesis, although biologically possible, has thus far
      not been sufficiently well proven to support the everyday use of these 2 drug
      classes in combination. Additional outcomes trials, which are currently
      proceeding to their conclusion, may provide the necessary proof to support an
      expanded use of these 2 drug classes in combination.

PMID- 17215669
TI  - How to implement a laptop computer requirement: lessons learned.

PMID- 17215670
TI  - PowerPoint pedagogy: two usages, two pedagogical styles.

PMID- 17215671
TI  - MERLOT delivered to your desk.

PMID- 17215672
TI  - What adolescents with type I diabetes and their parents want from testing
      technology: a qualitative study.
AB  - The presence of diabetes in an adolescent can significantly affect his/her normal
      development. Mobile technology may offer the ability to lessen this negative
      impact. We wished to learn from adolescents with diabetes and their parents how
      monitoring systems that incorporated mobile communication technology could
      potentially help to reduce hassles associated with testing, improve compliance,
      and ease adolescent-parent conflict about testing behavior. We recruited
      adolescents between the ages of 13 and 18 years, living with type 1 diabetes
      mellitus and their parents for focus groups. Qualitative analysis of the focus
      group data followed a set procedure. From the discussions, the following themes
      were identified: issues with blood glucose monitoring and desired technology.
      Elements of desired technology included hardware requirements, software
      requirements, communication, and miscellaneous requirements. The reported needs
      of this end-user group can help others to leverage maximally the capabilities of
      new and existing technology to care for children managing chronic disease.

PMID- 17215673
TI  - Computer literacy in baccalaureate nursing students during the last 8 years.
AB  - With the rapid integration of information technology in the healthcare field,
      equipping nurses with skills to effectively use the technology is vital.
      Evaluations of nursing students' nursing informatics competencies are scarce in
      nursing programs as reported in the literature. The current study was implemented
      to evaluate the self-reported nursing informatics competence of undergraduate
      baccalaureate students upon admission and graduation in the years from 1997 to
      2005 and to compare the differences between admission and graduation. The
      Gassert/McDowell Computer Literacy Survey was used to survey 411 students on
      admission and 429 students on graduation from a baccalaureate nursing program.
      Results showed a significant increase during the 8-year period, both on admission
      and graduation, for reported level of experience with word processing, electronic
      mail, and World Wide Web. Areas of less experience that did not increase
      significantly were spreadsheet experience, database experience, and use of
      statistical programs. The nursing informatics competencies established for
      beginning nurses include databases, spreadsheets, word processing, presentation
      graphics, and keyboard skills. The results of this study indicate nursing
      education programs currently may not be providing beginning nurses with the tools
      needed to effectively and efficiently work in the technology-rich healthcare
      arena.

PMID- 17215675
TI  - Collaborative practice: usability of text-based, electronic patient care
      guidelines.
AB  - The Intermountain Healthcare system has developed a text-based, electronic
      reference system for nonphysician staff to provide patient care guidelines
      intended to reduce variability in bedside care processes and improve patient
      outcomes. Implementation issues with two interface tools used to deploy the
      electronic documents at the bedside have caused difficulty with document
      accessibility. A third interface tool (Viewer) was designed to solve the
      accessibility problems. This study was designed to compare the time spent
      searching for information and success of information retrieval from all three
      interfaces before clinical deployment of the Viewer interface. Study results were
      used by nursing leadership in a decision to continue supporting the electronic
      dissemination of text-based practice guidelines for nonphysician staff within our
      health system's acute care settings.

PMID- 17215676
TI  - A cluster analysis to investigating nurses' knowledge, attitudes, and skills
      regarding the clinical management system.
AB  - Nurses' knowledge, attitudes, and skills regarding the Clinical Management System
      are explored by identifying profiles of nurses working in Hong Kong. A total of
      282 nurses from four hospitals completed a self-reported questionnaire during the
      period from December 2004 to May 2005. Two-step cluster analysis yielded two
      clusters. The first cluster (n = 159, 56.4%) was labeled "negative attitudes,
      less skillful, and average knowledge" group. The second cluster (n = 123, 43.6%)
      was labeled "positive attitudes, good knowledge, but less skillful." There was a
      positive correlation in cluster 1 for nurses' knowledge and attitudes (rs = 0.28)
      and in cluster 2 for nurses' skills and attitudes (rs = 0.25) toward
      computerization. The study showed that senior and more highly educated nurses
      generally held more positive attitudes to computerization, whereas the attitudes
      among younger and less well educated nurses generally were more negative. Such
      findings should be used to formulate strategies to encourage nurses to resolve
      actual problems following computer training and to increase the depth and breadth
      of nurses' computer knowledge and skills and improve their attitudes toward
      computerization.

PMID- 17215677
TI  - 2006 TIGER Summit: evidence and informatics transforming nursing.

PMID- 17215678
TI  - AMIA 2006.

PMID- 17215679
TI  - Interview with an informatics nurse.

PMID- 17215681
TI  - Balance control: looking forwards to feedforward.

PMID- 17215682
TI  - Imaging anatomy of the vestibular and visual systems.
AB  - PURPOSE OF REVIEW: This review will outline the imaging anatomy of the vestibular
      and visual pathways, using computed tomography and magnetic resonance imaging,
      with emphasis on the more recent developments in neuroimaging. RECENT FINDINGS:
      Technical advances in computed tomography and magnetic resonance imaging, such as
      the advent of multislice computed tomography and newer magnetic resonance imaging
      techniques such as T2-weighted magnetic resonance cisternography, have improved
      the imaging of the vestibular and visual pathways, allowing better visualization
      of the end organs and peripheral nerves. Higher field strength magnetic resonance
      imaging is a promising tool, which has been used to evaluate and resolve fine
      anatomic detail in vitro, as in the labyrinth. Advanced magnetic resonance
      imaging techniques such as functional magnetic resonance imaging and diffusion
      tractography have been used to identify cortical areas of activation and
      associated white matter pathways, and show potential for the future
      identification of complex neuronal relays involved in integrating these pathways.
      SUMMARY: The assessment of the various components of the vestibular and the
      visual systems has improved with more detailed research on the imaging anatomy of
      these systems, the advent of high field magnetic resonance scanners and
      multislice computerized tomography, and the wider use of specific techniques such
      as tractography which displays white matter tracts not directly accessible until
      now.

PMID- 17215683
TI  - Functional brain imaging: a window into the visuo-vestibular systems.
AB  - PURPOSE OF REVIEW: Advances have been made in identifying how areas involved in
      processing vestibular, ocular motor, and visual information are represented in
      the human cortex as well as the cortical interaction between these systems in
      healthy subjects. RECENT FINDINGS: While we know how some vestibular and ocular
      motor disorders modify visuo-vestibular interaction by changing the 'normal'
      cortical activation-deactivation patterns, it is still early days in functional
      magnetic resonance imaging studies of patients with specific disorders. Findings
      from current brain imaging studies of several vestibular, ocular motor, and
      cerebellar disorders are presented. SUMMARY: The promise of more insights into
      the complex neuronal networks of the human cortex is great.

PMID- 17215684
TI  - Vestibular function testing.
AB  - PURPOSE OF REVIEW: This review provides an overview of vestibular function
      testing and highlights the new techniques that have emerged during the past 5
      years. RECENT FINDINGS: Since the introduction of video-oculography as an
      alternative to electro-oculography for the assessment of vestibular-induced eye
      movements, the investigation of the utricle has become a part of vestibular
      function testing, using unilateral centrifugation. Vestibular evoked myogenic
      potentials have become an important test for assessing saccular function,
      although further standardization and methodological issues remain to be
      clarified. Galvanic stimulation of the labyrinth also is an evolving test that
      may become useful diagnostically. SUMMARY: A basic vestibular function testing
      battery that includes ocular motor tests, caloric testing, positional testing,
      and earth-vertical axis rotational testing focuses on the horizontal semicircular
      canal. Newer methods to investigate the otolith organs are being developed. These
      new tests, when combined with standard testing, will provide a more comprehensive
      assessment of the complex vestibular organ.

PMID- 17215685
TI  - An update on opsoclonus.
AB  - PURPOSE OF REVIEW: The aim of this article is to review opsoclonus, with
      particular emphasis on its immunopathogenesis and pathophysiology. RECENT
      FINDINGS: Infections (West Nile virus, Lyme disease), neoplasms (non-Hodgkin's
      lymphoma, renal adenocarcinoma), celiac disease, and allogeneic hematopoietic
      stem cell transplantation can cause opsoclonus. Newly identified autoantibodies
      include antineuroleukin, antigliadin, antiendomysial, and anti-CV2. Evidence
      suggests that the autoantigens of opsoclonus reside in postsynaptic density, or
      on the cell surface of neurons or neuroblastoma cells (where they exert
      antiproliferative and proapoptotic effects). Most patients, however, are
      seronegative for autoantibodies. Cell-mediated immunity may also play a role,
      with B and T-cell recruitment in the cerebrospinal fluid linked to neurological
      signs. Rituximab, an anti-CD20 monoclonal antibody, seems efficacious as an
      adjunctive therapy. Although changes in synaptic weighting of saccadic burst
      neuron circuits in the brainstem have been implicated, disinhibition of the
      fastigial nucleus in the cerebellum, or damage to afferent projections to the
      fastigial nucleus, is a more plausible pathophysiologic mechanism which is
      supported by functional magnetic resonance imaging findings in patients. SUMMARY:
      There is increasing recognition that both humoral and cell mediated immune
      mechanisms are involved in the pathogenesis of opsoclonus. Further studies are
      needed to further elucidate its immunopathogenesis and pathophysiology in order
      to develop novel and efficacious therapy.

PMID- 17215687
TI  - Epidemiology of vertigo.
AB  - PURPOSE OF REVIEW: Epidemiological findings on the distribution, determinants and
      outcome of vertigo can be used for clinical decision making and can help
      understand the underlying causes of vestibular diseases. This article gives an
      overview of the epidemiology of the vestibular symptom vertigo and of four
      specific vestibular disorders: benign paroxysmal positional vertigo, migrainous
      vertigo, Meniere's disease and vestibular neuritis. RECENT FINDINGS: Based on a
      neurotologic survey of the general population, 1-year prevalence estimates for
      vertigo were 4.9%, for migrainous vertigo 0.89% and for benign paroxysmal
      positional vertigo 1.6%. Diagnostic positional manoeuvres and treatments for
      benign paroxysmal positional vertigo, however, are still not being done by most
      doctors. The female preponderance among patients with benign paroxysmal
      positional vertigo and migrainous vertigo may be linked to migraine but is not
      fully understood. A recently reported prevalence of Meniere's disease of 0.51% is
      much higher than previous estimates. Follow-up studies have shown benign
      paroxysmal positional vertigo recurrence rates of 50% at 5 years and a
      persistence of dizziness related to anxiety in almost a third of patients 1 year
      after vestibular neuritis. SUMMARY: The epidemiology of vertigo and vestibular
      disorders is still an underdeveloped field. Recent studies have underscored the
      impact of vertigo at the population level, but its determinants and outcome are
      not well known yet.

PMID- 17215686
TI  - Neuro-otological emergencies.
AB  - PURPOSE OF THE REVIEW: Physicians find acute vertigo a diagnostic challenge. This
      article review recent evidence outlining the clinical presentation of acute
      central and peripheral dizzy syndromes and suggest when clinicians may consider
      acute neuro-imaging. RECENT FINDINGS: Recent evidence highlights the difficulty
      that acute vertigo may sometimes pose to the clinician. For example, migrainous
      vertigo may have oculomotor abnormalities suggestive of either central
      neurological or peripheral vestibular dysfunction. Furthermore, vertebrobasilar
      stroke syndromes may mimic peripheral disorders such as vestibular neuritis, or
      when there is hearing involvement may be misdiagnosed as Meniere's disease. In
      addition to the need for identifying serious conditions in acute vertigo, recent
      evidence suggests that early steroid treatment in vestibular neuritis may improve
      long term outcome. Further trials regarding symptomatic outcome are required,
      however, before routine use of steroids can be recommended in this condition.
      SUMMARY: Recent findings have not made the assessment of acute vertigo any easier
      for the nonspecialist. Although the commonest vertigo syndromes are benign,
      serious conditions such as stroke may masquerade as a peripheral labyrinthine
      disorder and conversely benign conditions such as migrainous vertigo may have
      clinical characteristics of central disorders. These findings re-emphasize the
      need for a thorough clinical evaluation of the acutely dizzy patient.

PMID- 17215688
TI  - The complex dynamics of stroke onset and progression.
AB  - PURPOSE OF REVIEW: The aim of this article is to discuss the dynamic nature of
      cerebrovascular ischemia. RECENT FINDINGS: Acute risk factors are superimposed on
      chronic risk factors to precipitate plaque rupture in myocardial infarction. The
      interaction between external triggers, such as stress, with internal triggers,
      such as vasoconstriction, is mediated to a large part by the autonomic nervous
      system. Numerous algorithms have been developed to describe physiological time
      series data, for example heartbeat variability, and reveal complex structure that
      has diagnostic and prognostic significance. Much of this structure is mediated by
      the autonomic nervous system. Recent data on stroke triggers, carotid stenosis,
      transient ischemic attack, and infarct expansion suggest a similar need for
      detailed physiological measurement and non-linear dynamics in order to understand
      stroke onset and progression. SUMMARY: The picture emerging is that stroke arises
      as a result of multiple processes with different time constants. The nature and
      timing of interventions should be tailored to these complex interacting
      processes. This will require more frequent and varied physiological measurement
      accompanied by non-linear analytical methods. This new approach, which stresses
      complex within-subject measurements, will likely make 'one size fits all'
      solutions to stroke care untenable.

PMID- 17215689
TI  - Why now? Moving from stroke risk factors to stroke triggers.
AB  - PURPOSE OF REVIEW: While chronic risk factors for stroke are reasonably well
      understood, the acute precipitants, or triggers, of stroke, remain relatively
      understudied. RECENT FINDINGS: Several converging lines of evidence indicate that
      transient perturbations in systemic metabolism may provoke the onset of
      cardiovascular events, including stroke. Epidemiologic data, including studies
      utilizing novel designs that consider intraindividual differences across
      different time periods, have been used to clarify triggers for myocardial
      ischemia, and these methods are beginning to be employed in stroke research.
      Acute infections, particularly upper respiratory infections, and other
      inflammatory stimuli have emerged as important triggers of acute ischemic stroke.
      The mechanisms involved include immunologically mediated activation of platelets
      and endothelial dysfunction. There also appears to be a period of time, or
      'stroke-prone state', characterized by diffuse activation of the vasculature
      during which patients may be at increased risk of initial and recurrent ischemic
      events. SUMMARY: Confirmation of these findings in further studies may help
      elucidate the mechanisms behind this short-term increase in stroke risk. Improved
      methods of assessment of this period of heightened susceptibility could lead to
      more temporally focused preventive interventions.

PMID- 17215690
TI  - Asymptomatic carotid stenosis: what to do.
AB  - PURPOSE OF REVIEW: Patients with asymptomatic carotid stenosis are at increased
      vascular risk but optimal treatment is controversial. We reviewed the current
      evidence for medical and surgical intervention in these patients. RECENT
      FINDINGS: Optimal medical treatment is the most important aspect of management of
      patients with asymptomatic carotid stenosis. On the basis of previous trials,
      endarterectomy is only of overall benefit in men, and this benefit may now be
      obviated by improved medical treatment. There is insufficient evidence to
      advocate the routine use of carotid angioplasty or stenting in patients with
      asymptomatic stenosis. Inaccuracy in the measurement of carotid stenosis may
      contribute to conflicting estimates of stroke risk in relation to the degree of
      asymptomatic stenosis. Advances in noninvasive imaging of plaque morphology and
      inflammation and the detection of microembolic signals may help to risk stratify
      patients but data on clinical usefulness are lacking. SUMMARY: Absolute benefit
      from endarterectomy for asymptomatic carotid stenosis is small, but can sometimes
      be justified in men. Further research is required to determine long-term benefit
      in women and to risk stratify patients, particularly in the light of advances in
      medical treatment.

PMID- 17215691
TI  - Reversible brain ischemia: lessons from transient ischemic attack.
AB  - PURPOSE OF REVIEW: In recent years, there has been considerable scientific
      inquiry regarding transient ischemic attack. In an effort to synthesize at times
      conflicting data, this paper will review the recent evidence and provide a
      critical overview of reversible brain ischemia. RECENT FINDINGS: Transient
      ischemic attack is now understood to indicate a higher risk of recurrence than
      completed ischemic stroke. Efforts to unravel the mechanisms of this instability
      following transient ischemic attack using imaging studies have led to new
      concepts and definitions, and sparked further debate. While imaging has increased
      diagnostic certainty, it has yet to provide reliable prognostic markers. The
      evidence suggests that risk of clinical recurrence is most closely linked to the
      degree to which the initial deficit reverses. From a tissue level, however, there
      are also data to support the notion of a 'stroke-prone state' following both
      transient ischemic attack and completed stroke, suggesting that mechanistically
      they may be less distinct than previously thought. Transient ischemic attack may
      simply highlight the dynamic nature of all acute ischemic cerebrovascular
      syndromes. SUMMARY: Reversible brain ischemia is a harbinger for subsequent
      ischemic stroke. Although recent advances have focused on imaging markers, the
      most important predictor of risk following brain ischemia is degree of early
      clinical reversibility.

PMID- 17215692
TI  - Stroke and the statistics of the aspirin/clopidogrel secondary prevention trials.
AB  - PURPOSE OF REVIEW: Four randomized trials have investigated the combination of
      clopidogrel plus aspirin for secondary prevention of vascular outcomes in 54,949
      patients. Here we argue that attempts to translate the results of these trials
      into clinical practice have proven frustrating because of the following
      statistical considerations: differences in study populations and study design
      make comparisons difficult (comparisons of 'apples and oranges'), incomplete
      factorial designs prevent proper contrasts (examining 'bits and pieces' of a
      larger picture), results concern widely different vascular diseases ('puzzling
      subgroups'), and negative results are easily misinterpreted. RECENT FINDINGS:
      Between 1996 and 2004 three major randomized trials assessed combinations of
      aspirin and clopidogrel, finding: Clopidogrel versus Aspirin in Patients at Risk
      of Ischemic Events (CAPRIE) in favor of clopidogrel alone versus aspirin alone,
      Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) in favor of
      clopidogrel plus aspirin versus aspirin alone, and Management of Atherothombosis
      with Clopidogrel in High-risk Patients (MATCH) in favor of clopidogrel plus
      aspirin versus clopidogrel alone. A recently completed fourth trial (Clopidogrel
      for High Atherothrombotic Risk and Ischemic Stabilization, Management and
      Avoidance; CHARISMA) was a 'negative study' comparing aspirin alone to aspirin
      plus clopidogrel. SUMMARY: Even after four large randomized trials we still do
      not know the optimal treatment for secondary prevention of stroke. We suggest
      that subsequent trials should focus on a particular vascular disease and test
      hypotheses that relate to a specific mechanism.

PMID- 17215693
TI  - Why identification of stroke syndromes is still important.
AB  - PURPOSE OF REVIEW: Recent trends in the practice of stroke neurology lay a strong
      and excessive reliance on data generated from large epidemiological and clinical
      trials to direct patient care. This article highlights some of the pitfalls of
      this approach. It discusses the continuing importance of identifying stroke
      syndromes in implementing individualized patient care. RECENT FINDINGS: Stroke is
      a heterogeneous disease and occurs through a variety of mechanisms. With the help
      of examples, the article illustrates some of the complexities of clinical
      decision making in an individual patient. Some important recent advances in the
      diagnostic and treatment armamentarium for stroke are also discussed. SUMMARY:
      Identification of stroke syndromes remains an important tool in the rational
      management of stroke patients.

PMID- 17215694
TI  - Bibliography. Current world literature. Neuro-ophthalmology and neuro-otology.

PMID- 17215696
TI  - Pharmacogenetics and obstetric anesthesia.

PMID- 17215697
TI  - Amniotic fluid embolism.

PMID- 17215698
TI  - HIV and pregnancy: twenty-five years into the epidemic.

PMID- 17215699
TI  - Anesthetic management for the morbidly obese pregnant woman.

PMID- 17215700
TI  - The anticoagulated parturient.

PMID- 17215701
TI  - Patient-controlled epidural analgesia for labor.

PMID- 17215702
TI  - Anesthesia for assisted reproductive technologies.

PMID- 17215703
TI  - Obstetric anesthesia controversies: vasopressor choice for postspinal hypotension
      during cesarean delivery.

PMID- 17215704
TI  - Oral intake during labor.

PMID- 17215708
TI  - Fatigue in the U.S. workforce: prevalence and implications for lost productive
      work time.
AB  - OBJECTIVE: The objective of this study was to estimate fatigue prevalence and
      associated health-related lost productive time (LPT) in U.S. workers. METHODS:
      Fatigue prevalence, LPT due to fatigue, and LPT for any health-related reason (in
      hours and dollars) were measured in a national cross-sectional telephone survey
      of U.S. workers. RESULTS: The 2-week period prevalence of fatigue was 37.9%. Of
      workers with fatigue, 65.7% reported health-related LPT compared with 26.4% of
      those without fatigue. Workers with fatigue cost employers 136.4 billion dollars
      annually in health-related LPT, an excess of 101.0 billion dollars compared with
      workers without fatigue. Fatigue frequently co-occurs with other conditions and,
      when present, is associated with a threefold increase, on average, in the
      proportion of workers with condition-specific LPT. CONCLUSIONS: Fatigue is
      prevalent in the U.S. workforce. When occurring with other health conditions, it
      is associated with significantly more condition-specific LPT.

PMID- 17215709
TI  - Impacts of a smoking cessation benefit among employed populations.
AB  - OBJECTIVE: The objective of this study was to project the health and economic
      impacts of providing a workplace smoking cessation benefit. METHODS: The authors
      conducted an update of a previously published outcomes model using recently
      published data and clinical trial results. RESULTS: In four example workplace
      types evaluated, coverage of a cessation benefit resulted in greater numbers of
      successful cessations and decreased rates of smoking-related diseases. Total
      savings from benefit coverage (decreased healthcare and workplace costs) exceeded
      costs of the benefit within 4 years. Total savings per smoker ranged from 350
      dollars to 582 dollars at 10 years and 1152 dollars to 1743 dollars at 20 years.
      Internal rate of return ranged from 39% to 60% at 10 years. CONCLUSION: Providing
      a workplace smoking cessation benefit results in substantial health and economic
      benefits with economic savings exceeding the cost of the benefit within a
      relatively short period. CLINICAL SIGNIFICANCE: Providing a workplace smoking
      cessation benefit is projected to increase the rate of smoking cessation as well
      as decrease the incidence of smoking-related conditions and healthcare costs. In
      addition, workplace cessation benefits can result in decreased absenteeism,
      increased productivity, and net cost savings within 4 years.

PMID- 17215710
TI  - A retrospective analysis of disability and its related costs among employees with
      chronic obstructive pulmonary disease.
AB  - OBJECTIVE: The objective of this study was to examine the frequency and cost of
      disability among actively employed individuals with chronic obstructive pulmonary
      disease (COPD). METHODS: The authors conducted a retrospective analysis of
      disability and claims data. Employees 40 to 63 years old with a diagnosis of COPD
      between January 1, 2001, and March 31, 2004, were identified, and controls were
      matched 2:1 to these subjects. Likelihood and cost of disability were compared
      between cohorts. RESULTS: A total of 2696 controls were matched to 1349 COPD
      subjects. Mean age was 52 years, and cohorts were approximately 50% male. A
      significantly (P < 0.0001) greater proportion of COPD subjects used short-term
      (21.8% vs 7.0%), long-term (2.4% vs 0.4%), or any disability (22.8% vs 7.3%).
      Associated costs were also higher among COPD subjects (8559 dollars vs 5443
      dollars; P = 0.07). CONCLUSIONS: Within a population of actively employed
      individuals 40 to 63 years old, COPD was found to have a substantial impact on
      the frequency and cost of disability.

PMID- 17215711
TI  - Prognostic factors of long-term disability in a workers' compensation system.
AB  - OBJECTIVE: We identified predictive factors of long-term disability in new
      workers' compensation claims to guide secondary prevention research and target
      interventions for high-risk claims. METHODS: Workers with 4 or more days of work
      disability resulting from workplace injuries were followed for approximately 6
      years in a population-based retrospective inception cohort study of 81,077
      workers. RESULTS: Predictors of long-term disability included delay between
      injury and first medical treatment, older age, construction industry, logging
      occupation, longer time from medical treatment to claim filing, back injury,
      smaller firm size, female gender, higher unemployment rate, and having
      dependents. We used logistic and quantile regression to investigate predictors of
      disability. These models produced consistent information regarding predictors.
      CONCLUSION: These factors can be used to identify jobs or workers at increased
      risk for long-term disability that warrant prevention intervention.

PMID- 17215712
TI  - Computer algorithm for automated work group classification from free text: the
      DREAM technique.
AB  - OBJECTIVE: This study developed and tested a computer method to automatically
      assign subjects to aggregate work groups based on their free text work
      descriptions. METHODS: The Double Root Extended Automated Matcher (DREAM)
      algorithm classifies individuals based on pairs of subjects' free text word roots
      in common with those of standard classification systems and several explicitly
      defined linkages between term roots and aggregates. RESULTS: DREAM effectively
      analyzed free text from 5887 participants in a multisite chronic obstructive
      pulmonary disease prevention study (Lung Health Study). For a test set of 533
      cases, DREAMs classifications compared favorably with those of a four-human
      panel. The humans rated the accuracy of DREAM as good or better in 80% of the
      test cases. CONCLUSIONS: Automated text interpretation is a promising tool for
      analyzing large data sets for applications in data mining, research, and
      surveillance. Work descriptive information is most useful when it can link an
      individual to aggregate entities that have occupational health relevance.
      Determining the appropriate group requires considerable expertise. This article
      describes a new method for making such assignments using a computer algorithm to
      reduce dependence on the limited number of occupational health experts. In
      addition, computer algorithms foster consistency of assignments.

PMID- 17215713
TI  - Organizational climate and occupational health outcomes in hospital nurses.
AB  - OBJECTIVE: The objective of this study was to determine relationships between
      organizational climate (OC) factors and occupational health outcomes (lost
      workdays, musculoskeletal injury, blood and body fluid exposures, injuries, and
      burnout) among hospital-based nurses. METHODS: Measures were obtained through a
      self-administered, anonymous survey distributed in 13 New York City hospitals.
      Multivariate models appropriate for clustered data were developed. These analyses
      controlled for nurse and employment characteristics. Independent effects of OC
      factors were examined. RESULTS: Surveys from 2047 predominantly registered nurses
      were obtained (response rate 50%). More than 75% reported lost workdays due to
      illness in the previous 4-month period and over one third reported experiencing
      some type of injury. OC factors were independently associated with injuries and
      measures of burnout (P < or = 0.05). CONCLUSIONS: OC is significantly associated
      with the health and well-being of hospital nurses.

PMID- 17215714
TI  - Predicting treatment failure in the subacute injury phase using the Orebro
      Musculoskeletal Pain Questionnaire: an observational prospective study in a
      workers' compensation system.
AB  - OBJECTIVE: The goal of the present study was to examine if patient scores on a
      brief biopsychosocial screening questionnaire--the Orebro Musculoskeletal Pain
      Questionnaire (OMPQ)--could predict clinical discharge status ("fit" vs "not fit"
      for return to work) after a standardized 6-week physical therapy-based work
      conditioning program. METHODS: The OMPQ was administered to a derivation sample
      of 200 injured workers with soft tissue injuries before beginning treatment. A
      clinical cutoff score of 147 was subsequently tested in a second validation
      sample of 211 injured workers. RESULTS: The OMPQ was able to correctly predict
      the discharge status of 85% of claimants. CONCLUSIONS: These results suggest that
      the OMPQ can facilitate clinical decision-making through early identification of
      individuals likely to fail a unidisciplinary physical therapy program and who may
      benefit from more complete biopsychosocial treatment.

PMID- 17215715
TI  - Job strain and adverse health behaviors: the Finnish Public Sector Study.
AB  - OBJECTIVE: The objective of this study was to explore the association between job
      strain and the co-occurrence of adverse health behaviors; smoking, heavy
      drinking, obesity, and physical inactivity. METHODS: The authors studied cross
      sectional data of 34,058 female and 8154 male public sector employees. RESULTS:
      Multinomial logistic regression models adjusted for sex, age, basic education,
      marital status, and type of job contract showed that high job strain and passive
      jobs were associated with 1.3 to 1.4 times higher odds of having > or =3 (vs 0)
      adverse health behaviors. Among men, low job control was associated with a 1.3
      fold likelihood and among women active jobs were associated with a 1.2-fold
      likelihood of having > or =3 (vs 0) adverse behaviors. High demands were
      associated with a higher likelihood of co-occurrence of one to two (vs 0) adverse
      behaviors among women. CONCLUSIONS: Job strain conditions may be associated with
      the co-occurrence of adverse health behaviors that contribute to preventable
      chronic diseases. CLINICAL SIGNIFICANCE: Adverse job conditions may increase the
      likelihood of co-occurring health risk behaviors. Reducing work stress by
      increasing job control and decreasing psychologic demands might help efforts to
      promote healthy lifestyles.

PMID- 17215716
TI  - Smoking rate trends in U.S. occupational groups: the 1987 to 2004 National Health
      Interview Survey.
AB  - OBJECTIVE: It is unknown if the gap in smoking rates observed between United
      States blue- and white-collar workers over the past four decades has continued
      into the new millennium. METHODS: The National Health Interview Survey is a
      nationally representative survey of the US civilian population. Smoking and
      current occupational status were assessed over survey periods 1987 to 1994 and
      1997 to 2004 (n= 298,042). RESULTS: There were significant annual reductions in
      smoking rates for all adult US workers in both survey periods. Several blue
      collar groups had greater annual smoking rate reductions in the most recent
      survey period relative to the earlier survey period. However, the majority of
      blue-collar worker groups had pooled 1997 to 2004 smoking rates in excess of the
      24.5% smoking prevalence noted for all workers. CONCLUSION: Development of
      effective smoking prevention strategies specifically targeting blue-collar groups
      is warranted.

PMID- 17215717
TI  - Mortality patterns among workers exposed to acrylamide: updated follow up.
AB  - OBJECTIVE: The objective of this study was to update the mortality experience of
      a cohort of workers with and without potential exposure to acrylamide (AMD) at
      three U.S. plants (n = 8508) and one plant in The Netherlands (n = 344). METHODS:
      We computed standardized mortality ratios (SMRs) using national and local rates
      and modeled internal cohort rates to assess site-specific cancer risks by
      demographic and work history factors and several exposure indicators for AMD.
      RESULTS: For the 1925-2002 study period, we observed both deficit and excess
      overall mortality risks among the U.S. cohort for cancer sites implicated in
      experimental animal studies: brain and other central nervous system (SMR = 0.67,
      confidence interval [CI] = 0.40-1.05), thyroid gland (SMR = 1.38, CI = 0.28
      4.02), testis and other male genital organs (SMR = 0.64, CI = 0.08-2.30); and for
      sites selected in earlier exploratory analyses of this cohort: respiratory system
      cancer (RSC) (SMR = 1.17, CI = 1.06-1.27), esophagus (SMR = 1.20, CI = 0.86
      1.63), rectum (SMR = 1.25, CI = 0.84-1.78), pancreas (SMR = 0.94, CI = 0.70
      1.22), and kidney (SMR = 1.01, CI = 0.66-1.46). Except for RSC, attributed
      earlier to muriatic acid exposure, none of the mortality excesses was
      statistically significant. In the Dutch cohort, we observed deficits in deaths
      for all sites of a priori interest. An updated analysis of our previous
      exploratory findings for pancreatic cancer in the U.S. cohort revealed much less
      evidence of a possible exposure-response relationship with AMD. CONCLUSION: AMD
      exposure at the levels present in our study sites was not associated with
      elevated cancer mortality risks.

PMID- 17215718
TI  - Exposure to beryllium and occurrence of lung cancer: a reexamination of findings
      from a nested case-control study.
AB  - OBJECTIVE: Our aim was to reanalyze a nested case-control study of beryllium and
      lung cancer because we identified analysis and study design issues that could
      have led to the elevated odds ratios obtained in the study. METHODS: We
      reanalyzed the data using nontransformed exposure metrics instead of log
      transformed metrics used in the publication. We identified and examined effects
      on estimated odds ratios of imbalances between cases and controls caused by the
      control selection method. RESULTS: This reanalysis found no elevated odds ratios
      for any exposure variable. CONCLUSION: : Our conclusions differ from the authors'
      interpretation that the findings are due to a causal relationship between
      beryllium exposure and lung cancer. Our alternative explanation is that they may
      be due to methodological problems that could have been controlled by closer
      matching of controls to cases. CLINICAL SIGNIFICANCE: This study challenges
      conclusions made from a large case-control study concerning beryllium-lung cancer
      associations. Occupational medicine practitioners may want to integrate findings
      from this study into advice they give beryllium-exposed workers concerned about
      lung cancer.

PMID- 17215719
TI  - Why are river recreationalists most at risk for development of waterborne
      infectious diseases: how can clinicians improve surveillance? A national problem.

PMID- 17215721
TI  - Critically appraised topics: the evidence-based neurologist.

PMID- 17215722
TI  - Diagnosis and treatment of neuromyelitis optica.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is an uncommon CNS demyelinating syndrome
      often mistaken for severe multiple sclerosis (MS). Several clinical, laboratory,
      and neuroimaging characteristics may accurately distinguish NMO from MS early in
      the disease course. REVIEW SUMMARY: NMO is usually a relapsing disorder
      associated with early, severe, attack-related residual disability. It is
      associated with a highly specific antibody marker, NMO-IgG, which targets the
      water channel aquaporin-4. Revised NMO diagnostic criteria require optic
      neuritis, acute myelitis, and 2 of the following 3 characteristics: disease-onset
      brain magnetic resonance imaging (MRI) that is nondiagnostic for MS, contiguous
      spinal cord MRI lesion extending over 3 or more vertebral segments, and NMO-IgG
      seropositive status. Symptoms referable to central nervous system regions other
      than the optic nerve and spinal cord do not necessarily exclude the diagnosis of
      NMO, nor does the presence of brain MRI lesions. NMO-IgG has facilitated an
      appreciation that the spectrum of NMO is wider than previously recognized, and
      includes a proportion of patients with each of recurrent longitudinally extensive
      myelitis, recurrent isolated optic neuritis, and Japanese opticospinal MS. In
      contrast to typical MS, clinical experience and case series suggest that NMO
      requires long-term immunosuppressive therapy. CONCLUSIONS: NMO can be reliably
      differentiated from MS at an early stage using validated diagnostic criteria. The
      spectrum of NMO is wider than previously appreciated. Accurate, early diagnosis
      is critical to facilitate initiation of immunosuppressive therapy for attack
      prevention.

PMID- 17215723
TI  - Vasculitic neuropathies: an update.
AB  - BACKGROUND: Systemic vasculitis has been classically categorized as a primary
      disorder, such as polyarteritis nodosa, Churg-Strauss syndrome, and Wegener
      granulomatous, or as a secondary process, representing a complication from a
      connective tissue disorder (eg, rheumatoid vasculitis), infection, medication, or
      malignancy. Peripheral neuropathy is a well-recognized consequence of systemic
      vasculitis due to peripheral nerve infarction with Wallerian degeneration.
      Rarely, neuropathy is the sole manifestation of vasculitis, referred to as
      nonsystemic vasculitic neuropathy (NSVN). These conditions are defined
      pathologically by tissue biopsy demonstrating disruption or destruction of the
      vessel wall with inflammatory cell infiltrates. REVIEW SUMMARY: The diagnosis of
      vasculitic neuropathy is straightforward in patients with an established
      diagnosis of systemic vasculitis and classic features of mononeuritis multiplex.
      Most patients have clinical features of a subacute, progressive, generalized but
      asymmetric, painful, sensorimotor polyneuropathy. Laboratory tests often indicate
      features of systemic inflammation, such as an elevated sedimentation rate or
      positive anti-neutrophil cytoplasmic antibody, and electrodiagnostic evaluation
      shows multiple mononeuropathies or a confluent, asymmetric axonal neuropathy.
      Nerve biopsy is necessary to establish the diagnosis in most cases, particularly
      in patients with NSVN. This review summarizes the current treatment of vasculitic
      neuropathy. CONCLUSION: Long-term immunosuppressive therapy is required in most
      cases. High-dose prednisone combined with intravenous pulse or oral daily
      cyclophosphamide is standard initial therapy. In those with NSVN,
      cyclophosphamide also should be used if prednisone monotherapy is ineffective or
      the patient relapses with tapering. Other agents, such as azathioprine,
      methotrexate, intravenous immunoglobulin, mycophenolate mofetil, plasma exchange,
      and rituximab can be offered to patients who are intolerant or have a
      contraindication to cyclophosphamide. However, evidence for the benefit of these
      agents is limited to case reports and small case series.

PMID- 17215724
TI  - Nerve agents.
AB  - BACKGROUND: Nerve agents, the deadliest of the classic chemical warfare agents,
      primarily function as acetylcholinesterase inhibitors and cause a rapidly
      progressive cholinergic crisis. Originally developed for battlefield use, they
      have been used in terrorist attacks and are considered threats to the civilian
      population. REVIEW SUMMARY: The pathophysiology and clinical presentation of
      acute nerve agent poisoning are summarized and acute treatment protocols
      reviewed. Timely support and antidotal treatment are crucial and may be
      lifesaving. Pyridostigmine bromide, recently approved by the Food and Drug
      Administration as a pretreatment for soman poisoning, forms part of battlefield
      doctrine but is unlikely to be used in the civilian sector. Aside from that,
      civilian recommendations for acute therapy derive, with only minor modifications,
      from military doctrine. CONCLUSION: Neurologists should familiarize themselves
      with the pathophysiology and treatment principles for the syndromes caused by
      nerve agents, not only to assist with the hospital care of these patients but
      also to serve as resources to their local medical communities in preparation for
      chemical terrorism. Because nerve agents injure the nervous system,
      nonneurologists have a right to expect neurologists to have mastered these
      principles.

PMID- 17215725
TI  - Chronic progressive external ophthalmoplegia: a report of 6 cases and a review of
      the literature.
AB  - INTRODUCTION: Chronic progressive external ophthalmoplegia is a common
      mitochondrial disease that shares clinical, enzymatic, and genetic features with
      other mitochondrial disorders. Effective treatment does not exist, and corrective
      surgery of the ptosis as a palliative measure is a treatment option. PATIENTS AND
      METHODS: This was a retrospective study of 10 years' duration gathering patients
      with the diagnosis. Information related to clinical features, ancillary tests,
      and genetic data was obtained from our patients. RESULTS: Six patients were
      identified with this disease, 5 of them women, aged 44 to 72 years. All patients
      presented with ptosis, and in 50% of the patients it was asymmetric. Half of the
      patients noted mild dysphagia for liquids. The CPK and acetylcholine receptor
      antibody levels were normal. Jitter was increased in half of the patients and
      ragged-red fibers were present in 5 of them. The most common enzyme alteration
      was the combined deficit of complexes I and IV. Familial forms were not found
      among our patients. The most common genetic anomaly was a single deletion in the
      mitochondrial DNA. CONCLUSION: Knowledge of this disorder enables us to avoid the
      use of drugs with significant side effects in cases of ptosis and ophthalmoplegia
      that do not respond to anticholinesterases.

PMID- 17215727
TI  - Shingles.

PMID- 17215726
TI  - Treatment of vascular dementia and vascular cognitive impairment.
AB  - OBJECTIVE: In patients with vascular dementia and vascular cognitive impairment,
      are acetylcholinesterase inhibitors (donepezil, galantamine, and rivastigmine)
      and N-methyl-d-aspartate (NMDA) receptor antagonists (memantine) effective in
      improving cognitive function over placebo? METHODS: The question was addressed
      with a structured, evidence-based, clinical, neurologic practice review.
      Participants included consultant and resident neurologists, clinical
      epidemiologists, medical librarians, and clinical content experts. A critically
      appraised topic format was employed, with a clinical scenario, structured
      question, search strategy, appraisal, results, summary of evidence, commentary,
      and bottom-line conclusions. RESULTS: Eight relevant systematic reviews and
      randomized controlled trials were identified and served as the principal sources
      of information. The best evidence to date revealed that donepezil 5 mg/d [number
      needed to treat (NNT) = 10] was the most effective and best tolerated [number
      needed to harm (NNH) = 50] of the available agents. Galantamine 24 mg/d (NNT = 7)
      was also effective but less well tolerated (NNH = 7). Due to insufficient
      evidence, rivastigmine could not yet be recommended for the treatment of vascular
      dementia. Memantine appeared to be safe and well tolerated but did not
      demonstrate effectiveness across all cognitive outcomes and clinical global
      measures. CONCLUSION: Acetylcholinesterase inhibitors and NMDA receptor
      antagonists, in general, displayed promise as treatments for patients with
      vascular dementia and vascular cognitive impairment. The most effective, evidence
      based treatments were donepezil and galantamine.

PMID- 17215728
TI  - Crises and war: stepping stones to the future.

PMID- 17215730
TI  - Beta-blocker exposure is associated with improved survival after severe traumatic
      brain injury.
AB  - BACKGROUND: Beta-blocker use in elective noncardiac surgery has been associated
      with a reduction in mortality and cardiovascular complications. Traumatic brain
      injury (TBI) is often associated with a hyperadrenergic state. We hypothesized
      that adrenergic blockade would confer improved survival among TBI patients.
      METHODS: Retrospective review of the Trauma Registry of the American College of
      Surgeons database at a Level I trauma center was conducted. All trauma patients
      admitted from January 2004 to March 2005 with head Abbreviated Injury Scale score
      of 3 or greater were evaluated. Patients with length of stay <4 or >30 days were
      excluded. Beta-blocker exposure was defined as receiving beta-blockers for 2 or
      more consecutive days. RESULTS: In all, 420 patients met inclusion criteria: 174
      patients exposed to beta-blockers [BB(+)] and 246 not exposed [BB(-)]. Mean age
      in BB(+) group was 50 years and 36 years in BB(-) group (p < 0.001). Mean Injury
      Severity Score was 33.6 for BB(+) group and 30.8 for BB(-) group (p = 0.01).
      Predicted survival (by Trauma and Injury Severity Score) for BB(+) group was
      59.1% compared with 70.3% for BB(-) group (p < 0.001). Observed mortality for
      BB(+) group was 5.1%, 10.8% for BB(-) group (p = 0.036). Adjusted incidence rate
      ratio of mortality among those exposed to beta-blockers compared with those not
      exposed was 0.29 (95% confidence interval). CONCLUSIONS: Beta-blocker exposure
      was associated with a significant reduction in mortality in patients with severe
      TBI. This reduction in mortality is even more impressive, considering that the
      BB(+) group was older, more severely injured, and had lower predicted survival.

PMID- 17215729
TI  - Practice patterns and outcomes of retrievable vena cava filters in trauma
      patients: an AAST multicenter study.
AB  - BACKGROUND: The purpose of this study is to describe practice patterns and
      outcomes of posttraumatic retrievable inferior vena caval filters (R-IVCF).
      METHODS: A retrospective review of R-IVCFs placed during 2004 at 21 participating
      centers with follow up to July 1, 2005 was performed. Primary outcomes included
      major complications (migration, pulmonary embolism [PE], and symptomatic caval
      occlusion) and reasons for failure to retrieve. RESULTS: Of 446 patients (69%
      male, 92% blunt trauma) receiving R-IVCFs, 76% for prophylactic indications and
      79% were placed by interventional radiology. Excluding 33 deaths, 152 were Gunter
      Tulip (G-T), 224 Recovery (R), and 37 Optease (Opt). Placement occurred 6 +/- 8
      days after admission and retrieval at 50 +/- 61 days. Follow up after discharge
      (5.7 +/- 4.3 months) was reported in 51%. Only 22% of R-IVCFs were retrieved. Of
      115 patients in whom retrieval was attempted, retrieval failed as a result of
      technical issues in 15 patients (10% of G-T, 14% of R, 27% of Opt) and because of
      significant residual thrombus within the filter in 10 patients (6% of G-T, 4% of
      R, 46% Opt). The primary reason R-IVCFs were not removed was because of loss to
      follow up (31%), which was sixfold higher (6% to 44%, p = 0.001) when the service
      placing the R-IVCF was not directly responsible for follow up. Complications did
      not correlate with mechanism, injury severity, service placing the R-IVCF, trauma
      volume, use of anticoagulation, age, or sex. Three cases of migration were
      recorded (all among R, 1.3%), two breakthrough PE (G-T 0.6% and R 0.4%) and six
      symptomatic caval occlusions (G-T 0, R 1%, Opt 11%) (p < 0.05 Opt versus both G-T
      and R). CONCLUSION: Most R-IVCFs are not retrieved. The service placing the R
      IVCF should be responsible for follow up. The Optease was associated with the
      greatest incidence of residual thrombus and symptomatic caval occlusion. The
      practice patterns of R-IVCF placement and retrieval should be re-examined.

PMID- 17215731
TI  - Mismatch recovery of regional cerebral blood flow and brain temperature during
      reperfusion after prolonged brain ischemia in gerbils.
AB  - BACKGROUND: Recovery of cerebral reperfusion after stroke or cardiac arrest can
      take a long time. We aimed to identify differences in the postischemic recovery
      of physiologic parameters between short and prolonged brain ischemia. METHODS:
      Eighteen Mongolian gerbils were assigned to one of three groups: 5-minute (G5),
      15-minute (G15), or 30-minute (G30) ischemia. With the use of our original
      microspectroscopy system, global ischemic reperfusion was performed. We measured
      changes in regional cerebral blood flow (r-CBF), microvessel diameter, and brain
      temperature (BrT) simultaneously. We also monitored somatosensory evoked
      potentials (SEPs) to evaluate electrophysiologic response. RESULTS: Both G5 and
      G15 showed concurrent recovery of r-CBF and BrT with hyperemia and hyperthermia,
      respectively, 10 to 15 minutes after reperfusion. The increase in BrT was <1
      degree C and recovered to baseline within 60 minutes after reperfusion. In G30,
      recovery of r-CBF was significantly delayed relative to that of BrT. The increase
      in BrT was >2 degrees C, peaking approximately 15 minutes after reperfusion, and
      then maintained increases of >1 degree C for 120 minutes. SEPs in G5 and G15
      showed concomitant recovery with that of r-CBF, whereas SEP recovery in G30 was
      delayed relative to that of r-CBF, eventually disappearing. All except one of the
      G30 gerbils died within 24 hours, but all in G5 and G15 survived. CONCLUSIONS:
      These results suggest that mismatch recovery of r-CBF and BrT after prolonged
      ischemia initiates metabolic derangement in brain tissue, leading to the
      electrochemical dysfunction and mortality.

PMID- 17215732
TI  - Tissue oxygen saturation predicts the development of organ dysfunction during
      traumatic shock resuscitation.
AB  - BACKGROUND: Near-infrared spectroscopy (NIRS) can continuously and noninvasively
      monitor tissue oxygen saturation (StO2) in muscle and may be an indicator of
      shock severity. Our purpose was to evaluate how well StO2 predicted outcome in
      high-risk torso trauma patients presenting in shock. METHODS: The primary outcome
      in this prospective study was multiple organ dysfunction syndrome (MODS). StO2
      data were obtained upon hospital arrival and for 24 hours along with other known
      predictors of hypoperfusion and clinical outcomes. Clinicians were blinded to
      StO2 measurements. RESULTS: Seven Level I trauma centers enrolled 383 patients,
      50 of whom developed MODS. Minimum StO2 performed similarly to maximum base
      deficit (BD) in discrimination of MODS patients. The sensitivity for both
      measures (StO2 cutoff = 75%; BD cutoff = 6 mEq/L) was 78%, the specificity was
      34% to 39%, the positive predictive value was 18% to 20% and the negative
      predictive value was 88% to 91%. StO2 and BD were also comparable in predicting
      death. CONCLUSIONS: NIRS-derived muscle StO2 measurements perform similarly to BD
      in identifying poor perfusion and predicting the development of MODS or death
      after severe torso trauma, yet have the additional advantages of being continuous
      and noninvasive.

PMID- 17215733
TI  - Beta-blocker use is associated with improved outcomes in adult trauma patients.
AB  - BACKGROUND: Beta-adrenoreceptor blocker (beta-blocker) therapy may improve
      outcomes in surgical patients by decreasing cardiac oxygen consumption and
      hypermetabolism. Because beta-blockers can lower the systemic blood pressure and
      cerebral perfusion pressure, there is concern regarding their use in patients
      with head injury. However, beta-blockers may protect beta-receptor rich brain
      cells by attenuating cerebral oxygen consumption and metabolism. We hypothesized
      that beta-blockers are safe in trauma patients, even if they have suffered a
      significant head injury. METHODS: Using pharmacy and trauma registry data of a
      Level I trauma center, we identified a cohort of trauma patients who received
      beta-blockers during their hospital stay (beta-cohort). Trauma admissions who did
      not receive beta-blockers were in the control cohort. beta-blocker status, in
      combination with other variables associated with mortality, were placed in a
      stepwise multivariate logistic regression to identify independent predictors of
      fatal outcome. RESULTS: In all, 303 (7%) of 4,117 trauma patients received beta
      blockers. In the beta-cohort, 45% of patients were on beta-blockers preinjury.
      The most common reason to initiate beta-blocker therapy was blood pressure (60%)
      and heart rate (20%) control. The overall mortality rate was 5.6% and head injury
      was considered to be the major cause of death. After adjusting for age, Injury
      Severity Scale score, blood pressure, Glasgow Coma Scale score, respiratory
      status, and mechanism of injury, the odds ratio for fatal outcome was 0.3 (p <
      0.001) for beta-cohort as compared with control. Decreased risk of fatal outcome
      was more pronounced in patients with a significant head injury. CONCLUSIONS: beta
      blocker therapy is safe and may be beneficial in selected trauma patients with or
      without head injury. Further studies looking at beta-blocker therapy in trauma
      patients and their effect on cerebral metabolism are warranted.

PMID- 17215734
TI  - Requests for 692 transfers to an academic level I trauma center: implications of
      the emergency medical treatment and active labor act.
AB  - BACKGROUND: The Emergency Medical Treatment and Active Labor Act (EMTALA)
      effectively requires Level I trauma centers (TC) to accept all transfers for a
      higher level of care if capacity exists. We hypothesized that EMTALA would burden
      a Level I TC by a selective referral of a poor payer mix of primarily
      nonoperative patients. METHODS: All transfer calls (December 2003 and September
      2005) to our Level I TC are handled by a dedicated transfer center. Calls were
      reviewed for age, surgical service requested, and outcome of request. The trauma
      registry was queried to compare Injury Severity Scale (ISS) score, hospital stay
      (LOS), operations, mortality, and payer status for transfer and primary catchment
      patients. RESULTS: In all, 821 calls were received; 77 calls were cancelled by
      the referring hospital and 52 were for consultation only. Of the 692 transfer
      requests, 534 (77%) were accepted, 134 (19%) were denied for no capacity, and
      only 24 (4%) were declined by TC as not clinically indicated. Transferred
      patients were younger (32.0 +/- 1.49 versus 38.9 +/- 0.51, p < 0.05), had similar
      ISS scores (13.6 +/- 0.62 versus 13.7 +/- 0.26) and LOS (7.0 +/- 0.70 versus 7.4
      +/- 0.25), but were somewhat more likely to require an operation than direct
      admissions (58% versus 51%, p < 0.05). Although trauma (24%) and neurosurgery
      (24%) were the most commonly requested services, followed by orthopedics (20%),
      orthopedics accounted for 60% of operations on transferred patients compared with
      10% to 13% for trauma and neurosurgery (mostly spine). There was no difference in
      the payer status of transfer and direct admit patients. CONCLUSIONS: Contrary to
      our assumptions, EMTALA patients had an identical payer mix and similar operative
      need compared with our primary catchment patients. They do represent a large
      additional patient load (20% of admissions) and differentially impact
      specialists, mostly operative for orthopedics and complex nonoperative care for
      trauma and neurosurgery. These data suggest that the primary motivations for
      transfer are specialist availability and complexity of care rather than financial
      concerns. As TCs provide backup specialty call coverage for a wide geographic
      area, this further supports the need for trauma systems development.

PMID- 17215735
TI  - Autopsy data in the peer review process improves outcomes analysis.
AB  - BACKGROUND: The value of autopsy findings has been questioned in peer review at
      mature trauma centers. We sought to determine the impact of autopsy data on the
      peer-review process. METHODS: This was a retrospective study. Data analyzed
      included mortality type (immediate/dead on arrival [DOA]; early [< or =48 hours];
      late [>48 hours]), Injury Severity Scale (ISS) score, Trauma and Injury Severity
      Score-generated probability of survival (PS), peer-review judgment of
      preventability, and findings at autopsy. Deaths were assigned to a category; then
      pre- and postautopsy ISS score, PS, and outcomes of the peer- review process
      (percent nonpreventable [%NP]) were compared. Paired t tests (alpha = 0.05) were
      performed to determine whether changes in ISS score and PS were statistically
      significant. All descriptive and inferential analyses were based on cases with
      pre- and postautopsy data for the relevant variables. RESULTS: Of the 170 deaths,
      126 deaths had an autopsy performed (74.1%) and 112 autopsy reports were
      available (89.9%). Autopsy data resulted in statistically significant changes in
      ISS score for each mortality category and in PS for the immediate/DOA and early
      categories. There were also autopsy- related changes in peer-review outcomes for
      immediate/DOA and late deaths but not for early deaths. The proportion of overall
      agreement between pre- and postautopsy outcomes for the immediate/DOA category
      was 94.3% (50/53); three deaths initially deemed NP were reclassified as
      potentially preventable (PP) after autopsy. Overall agreement for the late
      category was 87% (20/23); one PP was reclassified as NP and two NPs were
      reclassified as PP. CONCLUSION: Autopsy data enhanced peer review in
      immediate/DOA and late death after injury but did not impact peer review in early
      deaths. Autopsy data were most important to the analysis of late deaths.
      Targeting autopsy performance to these mortality categories is an effective
      strategy for centers with constrained access to autopsy data.

PMID- 17215736
TI  - What is the role of chest X-ray in the initial assessment of stable trauma
      patients?
AB  - BACKGROUND: The Advanced Trauma Life Support course advocates the liberal use of
      chest X-ray (CXR) during the initial evaluation of trauma patients. We reviewed
      CXR performed in the trauma resuscitation room (TR) to determine its usefulness.
      METHODS: A retrospective, registry-based review was conducted and included 1,000
      consecutive trauma patients who underwent CXR in the TR at a Level I trauma
      center during a 7-month period. RESULTS: Patients receiving CXR comprised 91.5%
      of all patients evaluated in the TR during the study period. CXR followed by
      chest computed tomography (CCT) was performed in 820 (82.0%) patients. Subsequent
      CCT identified missed findings in 235 (35.6%) of the 660 patients with an initial
      negative CXR who went on to receive CCT. CXR alone was performed in 127 (26.1%)
      of the 487 patients who were stable, not intubated, and had a normal chest
      physical examination (CPE). Seven patients (5.5%) in this group had potentially
      significant findings but none required intervention beyond physiotherapy or
      antibiotics. Three hundred and sixty (73.9%) of the 487 patients who were
      hemodynamically stable with a normal CPE underwent both CXR and CCT. Fifty-four
      patients (15%) in this group had findings of significance, and two (0.6%)
      required intervention. One patient received bilateral chest tubes for large pre
      existing pleural effusions found on CXR and CCT; another patient undergoing
      general anesthesia required a chest tube for a pneumothorax found only on CCT.
      CONCLUSION: In stable trauma patients with a normal CPE, CXR appears to be
      unnecessary in their initial evaluation. CXR should be relegated to a role
      similar to cervical spine and pelvis radiographs in the initial evaluation of
      hemodynamically stable trauma patients with a normal physical examination, and
      should be limited to use only for clear clinical indications.

PMID- 17215737
TI  - Long-term cognitive, emotional, and functional outcomes in trauma intensive care
      unit survivors without intracranial hemorrhage.
AB  - BACKGROUND: Trauma patients without intracranial hemorrhage or focal neurologic
      deficits are typically considered low risk for lasting neuropsychological and
      emotional deficits, and such sequela may be overlooked, especially in those with
      skull fractures and concussions. We undertook this study to determine the
      prevalence of and risk factors for persistent cognitive impairment and emotional
      and functional difficulties in a sample of adult trauma intensive care unit
      survivors without intracranial hemorrhage. METHODS: We queried the Vanderbilt
      University Trauma Registry for all patients admitted during 2003 with an Injury
      Severity Score >25 and a head computed tomography scan showing no intracranial
      hemorrhage. Of the 97 patients identified, 58 were evaluated, in person between
      12 to 24 months after hospital discharge, with a comprehensive battery of
      cognitive, emotional, and functional instruments. The Informant Questionnaire of
      Cognitive Decline in the Elderly-Short Form (IQCODE-SF) was used to evaluate for
      pre-existing cognitive deficits in patients suspected of having cognitive
      impairment before their trauma. RESULTS: A total of 33 (57%) patients were
      determined to have cognitive impairment, which was most pronounced in the domains
      of attention and executive functioning/verbal fluency. Of these patients, one
      (3%) was determined by the IQCODE-SF to be cognitively impaired before trauma
      intensive care unit hospitalization. Of the 58 patients studied, 21 (36.2%) had a
      concussion or skull fracture and 37 (63.8%) had neither. Cognitive impairment was
      significantly more likely to occur in patients who sustained a concussion or
      skull fracture than in trauma patients who did not (81% versus 43%; p = 0.006).
      Patients reported significant depressive symptoms (56%), significant symptoms of
      posttraumatic stress disorder (38%), and significant symptoms of anxiety (29%).
      Quality of life scores were lower than in the general United States population
      and employment difficulties were widespread. A total of 34% of patients reported
      being unemployed at follow-up, and cognitive impairment was more common among
      these patients compared with patients in the workforce (p = 0.03). Neither
      cognitive impairment nor emotional dysfunction was associated with age, sex,
      race, Injury Severity Score, blood loss, ventilatory days, or intramedullary
      nailing of long-bone fractures. CONCLUSIONS: The majority of trauma survivors
      without intracranial hemorrhage display persistent cognitive impairment, which is
      nearly twice as likely in those with skull fractures or concussions. This
      cognitive impairment was associated with functional defects, poor quality of
      life, and an inability to return to work. Future research must delineate
      modifiable risk factors for these poor outcomes, especially in patients with
      skull fractures and concussions, to help improve long-term cognitive and
      functional status.

PMID- 17215739
TI  - The potential utility of fibrin sealant dressing in repair of vascular injury in
      swine.
AB  - BACKGROUND: A previous study in which fibrin sealant dressing (FSD) secured
      hemostasis in major arterial hemorrhage for 96 hours suggested the applicability
      of this dressing in damage control operations after severe trauma. The objective
      of this study was to determine the effective duration of FSD hemostatic function
      in vivo and to examine its potential utility for definitive repair of a major
      arterial injury in swine. METHODS: High pressure bleeding in an infrarenal
      aortotomy was controlled by placing FSD on the wound with 4-minute compression (n
      = 15). If hemostasis was achieved, the abdominal cavity was closed. Surviving
      animals were killed at 2, 4, 6, and 8 weeks and aortotomy sites collected for
      histology. RESULTS: FSD stopped arterial hemorrhage after 4-minute compression in
      14 of 15 (93%) pigs. Dressings failed in two pigs at 36 and 53 minutes after
      treatment. Twelve (80%) animals recovered and resumed normal activities. Of the
      remaining 12, two developed rebleeding at the aortotomy site on days 8 and 11 and
      were killed; another was killed because of idiopathic low hematocrit on day 10.
      Nine pigs survived until scheduled to be killed, maintaining hemostasis with
      stable hematological values. In the surviving animals, serial computed tomography
      scans showed formation of a pseudoaneurysm at the aortotomy site, which resolved
      after 2 to 3 weeks. The initial vascular defect and pseudoaneurysm were filled
      with fibroblast-myoblast collagen rich tissues covered by endothelium.
      CONCLUSION: FSD can seal an arterial injury, stop high pressure bleeding, and
      prevent rebleeding for at least 7 days. The dressing may be most beneficial in
      damage control operations. If combined with an elective interventional radiologic
      procedure (e.g. embolization or stenting), it may also offer an alternative to
      suture repair of vascular injuries in cases where profuse bleeding obstructs
      visualization.

PMID- 17215738
TI  - Cytokine production in lipopolysaccharide-exposed rat lung pericytes.
AB  - BACKGROUND: Vessels of the pulmonary microvasculature are composed of two cell
      types: endothelial cells and pericytes. Pericytes are crucial to the development
      of capillary leak and pulmonary edema seen in acute respiratory distress syndrome
      (ARDS). Pericytes express toll-like receptor-4, and is upregulated in response to
      lipopolysaccharide (LPS). The objective of this study was to evaluate secretory
      cytokine production by rat microvascular pericytes. It is our hypothesis that
      pericytes secrete interleukin (IL)-1B, IL-6, and tumor necrosis factor (TNF)-A in
      response to LPS. METHODS: Rat lung pericytes (RLPs) were isolated and grown
      either alone or in coculture with rat endothelial cells. Cells from passages 3 to
      5 were used and treated with LPS (control, 10 ng/mL, and 100 ng/mL) for varying
      amounts of time. Immunoblotting and reverse transcriptase polymerase chain
      reaction (RT-PCR) was used for detection and quantification of NF-kB. Enzyme
      linked immunosorbent assay and RT-PCR were used for detection and quantification
      of cytokines. RESULTS: The protein and mRNA for NF-kB was detected in RLPs.
      Additionally, NF-kB mRNA increased with exposure to LPS. The supernatant of RLPs
      exposed to LPS contained IL-1B, and IL-1B increased in a time- and dose-dependant
      manner. An increase in mRNA for IL-1B, IL-6, and TNF-A was seen in a dose
      dependant fashion. Cocultures produced significantly less IL-1B when exposed to
      similar concentrations of LPS. CONCLUSIONS: Pericytes contain the machinery
      necessary, and produce pro-inflammatory cytokines. Cocultures manufacture less IL
      1B then pericytes alone, which is similar to previous coculture observations.
      Pericyte activation and cytokine production may play a role in capillary leak
      seen in gram-negative sepsis.

PMID- 17215740
TI  - Hypertonic saline and pentoxifylline reduces hemorrhagic shock resuscitation
      induced pulmonary inflammation through attenuation of neutrophil degranulation
      and proinflammatory mediator synthesis.
AB  - BACKGROUND: Ringer's lactate (RL), the current standard resuscitation fluid,
      potentiates neutrophil activation and is associated with pulmonary inflammation.
      Resuscitation with hypertonic saline and pentoxifylline (HSPTX) has been shown to
      attenuate hemorrhagic shock-induced injury when compared with RL. Because the
      neutrophil plays a major role in postshock inflammation, we hypothesized that
      HSPTX reduces pulmonary inflammation after resuscitation in comparison to RL.
      METHODS: Sprague-Dawley rats underwent controlled shock and were resuscitated
      with RL (32 mL/kg) or HSPTX (4 mL/kg 7.5% NaCl + pentoxifylline 25 mg/kg).
      Animals who did not undergo shock or resuscitation served as controls. After 24
      hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected.
      Cytokine induced neutrophil chemoattractant (CINC) was measured in BALF by enzyme
      linked immunosorbent assay. Matrix metalloproteinases (MMP)-2 and -9 were
      measured by zymography. Hemeoxygenase-1 (HO-1) was assessed by Western blot and
      immunohistochemistry. RESULTS: HSPTX resuscitation led to a 62% decrease in CINC
      levels compared with RL (p < 0.01). BALF MMP-2 expression was attenuated by 11%
      with HSPTX (p = 0.09). Lung MMP-2 and MMP-9 expression was reduced by 89% (p <
      0.01) and 76%, respectively (p < 0.05). Lung HO-1 expression declined by 34% with
      HSPTX in comparison to RL (p < 0.01), indicating less oxidative injury. Lung
      immunohistochemistry localized HO-1 to neutrophils, macrophages, and airway
      epithelial cells. CONCLUSION: Collectively, the attenuation of pulmonary
      inflammation with HSPTX after shock when compared with RL is associated with
      downregulation of neutrophil activation, oxidative stress, and proinflammatory
      mediator production.

PMID- 17215741
TI  - Fresh frozen plasma should be given earlier to patients requiring massive
      transfusion.
AB  - BACKGROUND: Acidosis, hypothermia, and coagulopathy were identified more than 20
      years ago as a deadly triad for patients presenting with exsanguinating
      hemorrhage. This led to fundamental changes in initial management of severely
      injured patients. Despite major advances, hemorrhage remains a leading cause of
      early death in trauma patients. Recent studies report most severely injured
      patients to be coagulopathic at admission, before resuscitation interventions,
      and that traditional massive transfusion practice grossly underestimates needs.
      The hypothesis for this study is that our pre-intensive care unit (ICU) massive
      transfusion (MT) protocol does not adequately correct coagulopathy, and that
      early uncorrected coagulopathy is predictive of mortality. METHODS: Data
      maintained in our Trauma Research Database were reviewed. Univariate logistic
      regression analysis was used to analyze the association of early ICU
      international normalized ratio (INR) and outcomes, including survival. RESULTS:
      Ninety-seven of 200 patients admitted during 51 months (ending January 2003) and
      resuscitated using our standardized ICU shock resuscitation protocol received MT
      (> or =10 units packed red blood cells [PRBC]) during hospital day 1 (age, 39 +/-
      2; ISS, 29 +/- 1; survival, 70%.) All patients required emergency operating room
      and/or interventional radiology procedures and arrived in the ICU 6.8 +/- 0.3
      hours after admission. Coagulopathy, present at hospital admission (pre-ICU INR,
      1.8 +/- 0.2), persisted at ICU admission (initial ICU INR, 1.6 +/- 0.1). Pre-ICU
      resuscitation, 9 +/- 1 L crystalloid fluid, 12 +/- 1 units PRBC, 5 +/- 0.4 units
      fresh frozen plasma (FFP), was consistent with our MT protocol by which FFP was
      not given until after 6 units PRBC. ICU resuscitation involved 11 +/- 1 L
      lactated Ringer's solution (LR) and 10 +/- 1 units PRBC. Mean pH was normal
      within 8 hours. Mean temperature increased from approximately 35 degrees C to >37
      degrees C within 4 hours. In the ICU during resuscitation, patients received 10
      +/- 1 units FFP for coagulopathy; the ratio of FFP:PRBC was 1:1. Mean INR
      decreased to 1.4 +/- 0.03 within 8 hours and remained nearly constant for the
      remaining 16 hours of ICU resuscitation, indicating moderate coagulopathy.
      Statistical analysis found severity of coagulopathy (INR) at ICU admission
      associated with survival outcome (p = 0.02; area under receiver operator curve
      [ROC] = 0.71.) CONCLUSION: These data indicate acidosis and hypothermia to be
      well managed. Coagulopathy was not corrected in the ICU despite adherence to pre
      ICU MT and ICU protocols, likely because of inadequate pre-ICU intervention. More
      aggressive pre-ICU intervention to correct coagulopathy may be effective in
      decreasing PRBC requirement during ICU resuscitation, and, because of the
      association with increased mortality, could improve outcome. We have revised our
      pre-ICU MT protocol to emphasize early FFP in a FFP:PRBC ratio of 1:1. We think
      that treatment of coagulopathy can be improved with the development of
      standardized protocols, both empiric and data driven.

PMID- 17215742
TI  - Sublingual capnometry for rapid determination of the severity of hemorrhagic
      shock.
AB  - BACKGROUND: Sublingual capnometry (SLCO2) is a rapid, minimally invasive bedside
      test of focal tissue perfusion. We hypothesized that SLCO2 could diagnose
      hemorrhagic shock and monitor adequacy of resuscitation. We compared the ability
      of SLCO2, serum lactate (LAC), and base deficit (BD) to predict outcome in
      hypotensive trauma patients. METHODS: Prospective, observational trial at two
      Level I trauma centers was performed. Inclusion criteria were blunt or
      penetrating trauma patients, age > or =16 years, with hypotension (systolic blood
      pressure < or =90 mm Hg). SLCO2, LAC, and BD were measured in each patient at
      admission, at the end of active hemorrhage, and at 6, 24, and 48 hours. Data are
      reported as means (+/-SD). RESULTS: A total of 86 patients were enrolled: mean
      age 35 (+/-17) years, 80% male, 51% blunt trauma, Injury Severity Score score 20
      (+/-14). Twenty patients died. SLCO2 at admission was 52.4 (+/-13.3) in survivors
      versus 87.9 (+/-35.6) in nonsurvivors (p < 0.001). Receiver operating
      characteristic (ROC) curves showed that SLCO2, LAC, and BD were all good
      predictors of mortality. The area under each ROC curve was as follows: SLCO2
      (0.82; 95% CI 0.70-0.96; p < 0.001), LAC (0.80; 95% CI 0.69-0.91; p < 0.001), BD
      (0.87; 95% CI 0.77-0.98; p < 0.001). There was no significant difference (p >
      0.05) in the areas under the three curves. CONCLUSIONS: SLCO2 predicted survival
      in hypotensive trauma patients. It had equivalent diagnostic ability to LAC and
      BD. This rapid test may supplement standard, more invasive measures of
      hemorrhagic shock.

PMID- 17215743
TI  - Beta-hydroxy-beta-methylbutyrate supplementation in critically ill trauma
      patients.
AB  - BACKGROUND: Negative nitrogen balance and skeletal muscle loss are common in
      critically injured patients and may contribute to morbidity, mortality and
      resource utilization. Juven, an enteral supplement which is a combination of beta
      hydroxy-beta-methylbutyrate (HMB), arginine (ARG), and glutamine (GLN) has been
      shown to restore muscle in cachetic acquired immunodeficiency syndrome (AIDS) and
      cancer patients. More recently HMB has been shown to attenuate cancer-induced
      muscle loss by decreasing muscle proteolysis. The purpose of this study was to
      analyze whether HMB alone or in combination with ARG and GLN would have a similar
      effect on critically injured trauma patients. We hypothesized that nitrogen
      balance would be improved and muscle proteolysis decreased with HMB and
      HMB/ARG/GLN supplementation. METHODS: There were 100 adult trauma patients with
      Injury Severity Score (ISS) >18 were enrolled in this prospective, randomized,
      blinded study. All patients received standard tube feeds and one of three iso
      nitrogenous supplements; HMB, HMB/ARG/ GLN, or placebo (PLAC) for 28 days. Urine,
      serum, and clinical data were collected for 72 patients receiving at least 7 days
      of supplementation during the first 14 days of treatment. Urinary 3
      methylhistidine (3-MH) was used as a proxy for muscle proteolysis. RESULTS: The
      three groups were similar in age, gender, mechanism, and severity of injury, with
      the average ISS being 31.9. Utilizing covariant (ISS) repeated measure (days 1
      14) mixed model (SAS) analysis, there was a significant treatment effect (p =
      0.05) on nitrogen balance (g/d). Change in nitrogen balance from the first 7 days
      to the last 7 days was -4.3 for the HMB and -5.6 g/d HMB/ARG/GLN groups compared
      with -8.9 g/d for the PLAC group. 3-MH to creatinine ratios were not different in
      the PLAC group as compared with the HMB/ARG/GLN and HMB groups (Treatment Effect,
      p = 0.80). CONCLUSIONS: These data suggest that supplementation with HMB alone
      may improve nitrogen balance in critically injured adult patients and that this
      effect is not a result of lowered muscle protein turnover as originally
      hypothesized.

PMID- 17215744
TI  - Functional outcome at 2.5, 5, 9, and 24 months after injury in the Netherlands.
AB  - BACKGROUND: The collection of empirical data on the frequency, severity, and
      duration of functioning is a prerequisite to identify patient groups with long
      term or permanent disability. METHODS: We fielded postal questionnaires in a
      stratified sample of 8,564 injury patients aged 15 years and older, who had
      visited an emergency department in the Netherlands. Measurements were at 2.5, 5,
      9, and 24 months after the injury and included a generic health status
      classification (EQ-5D), socio-demographic, and medical information. We analyzed
      determinants of long-term functional outcome by multivariate regression analysis.
      RESULTS: Five months after the injury health status of nonhospitalized injury
      patients was comparable to the general population's health (EQ-5D summary measure
      0.87). Health status of patients admitted for 3 days or less improved until 9
      months (0.82). For those admitted more than 3 days health status improved until
      24 months (0.48 toward 0.67), but remained below population norms.
      Hospitalization, age and sex (females), type of injury (spinal cord injury, hip
      fracture, and lower extremity injury), and comorbidity were significant
      predictors of poor functioning in the long term. CONCLUSIONS: Recovery patterns
      vary widely between nonhospitalized, shortly, and long hospitalized injury
      patients. Nonhospitalized injury patients recover within 5 months from an injury
      whereas a considerable group of hospitalized injury patients suffer from
      persistent health problems. Our study indicates the importance of health
      monitoring with an adapted longitudinal design for injury patients. The time
      intervals used should match the various stages of the recovery process, which
      depends on the severity of the injury studied.

PMID- 17215745
TI  - Preventable deaths from hemorrhage at a level I Canadian trauma center.
AB  - BACKGROUND: Studies of trauma deaths have had a tremendous impact on the quality
      of contemporary trauma care. We studied causes of trauma death at a Level I
      Canadian trauma center, and tabulated preventable deaths from hemorrhage using
      explicit criteria. METHODS: Trauma registry data were used to identify all trauma
      deaths at our institution from January 1, 1999 to December 31, 2003.
      Demographics, mechanism, and time or location of death were recorded. Registry
      data analysis and selective chart or autopsy review were then performed to assign
      causes of death. RESULTS: A total of 558 consecutive trauma deaths were reviewed.
      Mean age was 48.7 (46.7-50.6), and mean Injury Severity Score was 38.8 (37.6
      40.0); 29% were females. Blunt trauma represented 87% of all cases; penetrating
      injuries were only 13%. Central nervous system (CNS) injuries were the most
      frequent cause of death (60%), followed by hemorrhage (15%), and then combination
      CNS and hemorrhagic injuries (11%). Multiple organ failure caused 5% of deaths
      and 9% of deaths were from other causes. Of hemorrhagic deaths, 48% (n = 41) were
      from blunt injury, and 52% (n = 45) were from a penetrating mechanism. Of these
      hemorrhagic deaths, 16% were judged to be preventable because of significant
      delays in identifying the major source of hemorrhage. Hemorrhage from blunt
      pelvic injury was the major cause of exsanguination in 12 of 14 of these
      preventable deaths. CONCLUSIONS: Blunt injury is the major mechanism leading to
      trauma deaths. Massive bleeding from blunt pelvic injury is the major cause of
      preventable hemorrhagic deaths in our study.

PMID- 17215746
TI  - Survival after prolonged length of stay in a trauma intensive care unit.
AB  - BACKGROUND: Intensive care unit (ICU) patients comprise a small proportion of
      patients in the hospital but consume a disproportionate amount of hospital
      resources. In our cost-conscious environment, it becomes necessary to address the
      overall performance of our ICUs. This study was designed to analyze survival
      among trauma ICU (TICU) patients with a length of stay (LOS) >1 month. METHODS:
      We retrospectively reviewed the prospectively collected Trauma Registry Database
      between January 1, 1995, and January 1, 2005, in an adult TICU from a Level I
      trauma center. Data on demographics, mechanism of injury, Injury Severity Score
      (ISS), LOS, and in-hospital survival was collected. Descriptive statistics were
      calculated and student's t test and comparison of proportions were performed
      where appropriate. Logistic regression was performed to analyze independent
      predictors of mortality with significance when p < 0.05. RESULTS: The initial
      cohort consisted of 3,556 patients with a mean LOS of 9.8 days (range, 0-274
      days). Sixty-nine percent were men, mean age was 44.3 years (range, 0-104 years),
      and mean ISS was 18 (range, 0-75). The mechanism of injury was blunt trauma in
      75%, burns in 15%, and penetrating trauma in 10%. Overall survival was 87%. A
      total of 339 patients had a LOS >1 month. There was no difference in survival
      between patients with a LOS <1 month and those with a LOS >1 month (87.1% versus
      86.7%). Patients >50 years old (n = 1,251) had a longer LOS (12.5 versus 8.4
      days; p < 0.001) and increased mortality (22.1% versus 8.0%; p < 0.001). Age
      remained an independent predictor of mortality when controlling for ISS.
      CONCLUSION: In our TICU population, extended LOS did not preclude a significant
      chance of survival. Patients >50 years old had longer LOS and increased
      mortality. This suggests that the utilization of resources in patients with a
      prolonged LOS is reasonable and justified.

PMID- 17215747
TI  - Radiation exposure from diagnostic imaging in severely injured trauma patients.
AB  - BACKGROUND: Trauma patients often require multiple imaging tests, including
      computed tomography (CT) scans. CT scanning, however, is associated with high
      radiation doses. The purpose of this study was to measure the radiation doses
      trauma patients receive from diagnostic imaging. METHODS: A prospective cohort
      study was conducted from June 1, 2004 to March 31, 2005 at a Level I trauma
      center in Toronto, Canada. All trauma patients who arrived directly from the
      scene of injury and who survived to discharge were included. Three dosimeters
      were placed on each patient (neck, chest, and groin) before radiologic
      examination. Dosimeters were removed before discharge. Surface doses in
      millisieverts (mSv) at the neck, chest, and groin were measured. Total effective
      dose, thyroid, breast, and red bone marrow organ doses were then calculated.
      RESULTS: Trauma patients received a mean effective dose of 22.7 mSv. The standard
      "linear no threshold" (LNT) model used to extrapolate from effects observed at
      higher dose levels suggests that this would result in approximately 190
      additional cancer deaths in a population of 100,000 individuals so exposed. In
      addition, the thyroid received a mean dose of 58.5 mSv. Therefore, 4.4 additional
      fatal thyroid cancers would be expected per 100,000 persons. In all, 22% of all
      patients had a thyroid dose of over 100 mSv (mean, 156.3 mSv), meaning 11.7
      additional fatal thyroid cancers per 100,000 persons would result in this
      subgroup. CONCLUSION: Trauma patients are exposed to significant radiation doses
      from diagnostic imaging, resulting in a small but measurable excess cancer risk.
      This small individual risk may become a greater public health issue as more CT
      examinations are performed. Unnecessary CT scans should be avoided.

PMID- 17215748
TI  - Incidental CT findings in trauma patients: incidence and implications for care of
      the injured.
AB  - BACKGROUND: The evaluation of patients with head, neck, and torso trauma
      frequently includes high-definition spiral computed tomography (SCT) scanning,
      which can reveal non-injury-related lesions. These incidental findings vary in
      their importance, from trivial lesions to findings that may have a greater impact
      on the health of the trauma patient than the injuries that led to the SCT. We
      evaluated the incidence and clinical importance of incidental findings found on
      SCT, and the effectiveness of a trauma practice guideline calling for appropriate
      management and follow-up. METHODS: The trauma registry was accessed to identify
      patients evaluated at an urban Level I trauma center from January to November,
      2002. Trauma registry data, inpatient chart records, and the digital record of
      the filmless radiology archives were reviewed. Demographic data, including age,
      sex, type and mechanism of injury, and outcome, were recorded. All CT studies
      were reviewed for incidental findings. Mucus retention cysts, sinusitis (except
      mastoiditis), degenerative joint disease, evidence of previous operation, and age
      related cerebral atrophy were excluded. Incidental findings were divided into
      three categories based on clinical importance. Category 1 required attention
      before discharge. Category 2 required follow-up with primary doctor within 1 or 2
      weeks, and Category 3 required no specific follow-up. Categories 1 and 2 were
      considered clinically significant findings. RESULTS: Complete data were available
      for 991 patients (677 men, 314 women). Eight hundred and forty-eight (85.6%)
      patients received at least one CT scan. A total of 289 incidental findings were
      discovered. Thirty-one patients (3.1%) had 36 Category 1 findings. There were 108
      Category 2 and 145 Category 3 findings. When comparing those patients with at
      least one incidental finding, the incidence of incidental findings was higher in
      women than in men (34.1% versus 27.6%; p < 0.05). Older patients also had a
      higher incidence of all categories of findings (over 40 versus 40 and younger:
      46.1% versus 19.9%; p < 0.001). SCT yielded 90 (62.5%) of the clinically
      significant incidental findings in the abdomen/pelvis, 29 (20.1%) in the chest,
      and 25 (17.4%) in the head and neck. The charts of only 15 (48.4%) of the
      patients with Category 1 findings adequately documented the management of the
      incidental finding. CONCLUSIONS: SCT for the evaluation of trauma patients
      reveals a significant number of incidental findings. These lesions are common in
      the abdomen and pelvis and show an increased incidence in women and among older
      patients. Although many require early follow-up and specialty physician referral,
      there was insufficient documentation of the management of these injuries.
      Incidental findings in the injured remain a significant challenge for trauma
      centers. An organized approach is required for successful follow-up and
      management.

PMID- 17215749
TI  - The anterolateral thigh flap is highly effective for reconstruction of complex
      lower extremity trauma.
AB  - BACKGROUND: Trauma patients with high-energy injuries often present with severe
      tissue damage that extends beyond the immediate zone of injury and requires
      recruitment of vascularized tissues from distant sites. The objective of this
      study was to evaluate the utility of the anterolateral thigh (ALT) flap for
      reconstruction of the traumatically injured lower extremity. METHODS: Prospective
      data were collected on all patients who underwent lower extremity reconstruction
      with an ALT flap during a 3.5-year period at a primary adult resource center
      (PARC). Demographics captured included age, gender, Injury Severity Score,
      mechanism of injury, and size of defect and complications. RESULTS: Fifty-six
      patients underwent a total of 59 ALT flap harvests during the study period. The
      majority of patients were male (75%) and sustained blunt injury (95%). The mean
      age was 37 +/- 14 years with a mean Injury Severity Score of 17.9 +/- 8. The mean
      flap size was 20.7 x 8.4 cm, with 64% harvested from the injured limb. Total flap
      success rate was 91.5%, with four total (6.7%) and one partial flap failure
      (1.7%). CONCLUSION: The ALT flap is a useful tool for trauma reconstruction in
      lower extremity salvage. We have shown that the ALT flap can be performed
      successfully in the traumatically injured patient even when harvested from the
      ipsilateral lower extremity.

PMID- 17215750
TI  - Reconstruction of juxta-articular huge defects of distal femur with vascularized
      fibular bone graft and Ilizarov's distraction osteogenesis.
AB  - BACKGROUND: We evaluate the effect of reconstructing huge defects (mean, 15.8 cm)
      of the distal femur with Ilizarov's distraction osteogenesis and free twin
      barreled vascularized fibular bone graft (TVFG). METHODS: We retrospectively
      reviewed a consecutive series of five patients who had cases of distal femoral
      fractures with huge defects and infection that were treated by the Ilizarov's
      distraction osteogenesis. After radical debridement, two of the five cases had
      free TVFG and monolocal distraction osteogenesis, and another two cases had
      multilocal distraction osteogenesis with knee fusion because of loss of the joint
      congruity. The other case with floating knee injury had bilocal distraction
      osteogenesis and a preserved knee joint. The mean defect of distal femur was 15.8
      cm (range, 14-18 cm) in length. RESULTS: The mean length of distraction
      osteogenesis by Ilizarov's apparatus was 8.2 cm. The mean length of TVFG was 8
      cm. The average duration from application of Ilizarov's apparatus to achievement
      of bony union was 10.2 months (range, 8-13 months). At the end of the follow-up,
      ranges of motion of three knees were 0 to 45 degrees, 0 to 60 degrees, and 0 to
      90 degrees. Two cases had knee arthrodesis with bony fusion because of loss of
      the joint congruity. There were no leg length discrepancies in all five patients.
      In addition, three patients had pin tract infections and one case had a 10 degree
      varus deformity of the femur. CONCLUSIONS: Juxta-articular huge defect (>10 cm)
      of distal femur remains a challenge to orthopedic surgeons. Ilizarov's technique
      provides the capability to maintain stability, eradicate infection, restore leg
      length, and to perform adjuvant reconstructive procedure easily. In this study,
      we found that combining Ilizarov's distraction osteogenesis with TVFG results in
      improved patient outcome for patients with injuries such as supracondylar or
      intercondylar infected fractures or nonunion of distal femur with huge bone
      defect.

PMID- 17215751
TI  - Two-ring hybrid external fixation of distal tibial fractures: a review of 47
      cases.
AB  - BACKGROUND: The healing of a metaphyseal fracture line is a major problem in
      cases of distal tibial fracture treated with external fixation. METHODS: Forty
      seven distal tibial fractures treated with two-ring Ilizarov hybrid external
      fixation (16 AO/OTA type A and 31 type C, 10 open) were followed up. Fracture
      reduction and union time was evaluated and IOWA and RAND 36-Item Health Survey
      scores were used to assess functional outcome. RESULTS: Thirty-five fractures
      united uneventfully in a median time of 20 weeks, but 12 fractures needed
      additional procedures because of delayed union. According to univariate analysis,
      the risk factors for a longer time needed for fracture union were translational
      displacement and current smoking, and the risk factors for reoperation because of
      delayed union translational displacement fibular fracture fixation, and the
      number of cigarettes smoked per day. In multivariate analysis, translational
      displacement was a risk factor for both longer time to fracture union and
      reoperation and fibular fracture fixation was a risk factor for reoperation. If
      the translational displacement was less than 3 mm, the reoperation rate was 6%,
      whereas if the displacement was more than 3 mm, it was 83%. Reoperation was
      performed on 50% of the patients who underwent fibular fixation and on 15% of the
      patients who did not undergo fibular fixation. There were only marginal decreases
      in the range of motion and arthritis scores in the AO/OTA fracture types other
      than type C3. There were no significant differences in RAND 36 scores between the
      general Finnish population aged 18 to 64 years and our patients. CONCLUSIONS:
      Hybrid external fixation of distal tibial fractures is associated with delayed
      union, which is closely related to the degree of residual translational
      displacement after reduction. Fixation of an associated fibular fracture does not
      help to achieve better contact in the tibial fracture and increases the risk of
      delayed union.

PMID- 17215753
TI  - Ultrastructural changes of the cochlea after oral and maxillofacial firearm
      wounds.
AB  - BACKGROUND: There have been reports that maxillofacial firearm wounds could
      induce hearing loss. The effects on the ultrastructure of the cochlea and
      cochlear nerves after oral and maxillofacial firearm wounds are still unclear.
      This experiment investigates the ultrastructural changes of the cochlea and
      cochlear nerve after oral and maxillofacial firearm wounds. METHODS: Twenty dogs
      were wounded by steel spheres or detonators to establish animal models of oral
      and maxillofacial firearms wound. At different times after trauma, the wounds
      were examined and the specimens of the cochlea and cochlear nerve were taken to
      study the ultrastructural changes. RESULTS: The ultrastructural changes of the
      cochlea and cochlear nerve at 1 hour after trauma were cilia disorganization,
      edema of the nerve, and mitochondrial denaturalization. At 6 hours, there was
      extensive degeneration in the cochlea and cochlear nerve, cilia falling off of
      hair cells, and dissolution of the nerve sheath structure. CONCLUSIONS: The
      ultrastructure of the cochlea and cochlear nerve after injury is severe, but in
      the early period the injury is reversible.

PMID- 17215752
TI  - TENS relieves acute posttraumatic hip pain during emergency transport.
AB  - BACKGROUND: In Central Europe, ambulances for patients suffering from pain caused
      by nonlife-threatening trauma, such as hip fractures are staffed by medical
      personnel (medics) without physicians. Thus, there is an urgent need for
      nonpharmacological interventions that can be applied during the transport by
      basic life-support (BLS) medical personnel. METHODS: In all, 101 patients were
      screened for participation in this randomized placebo-controlled double-blind
      study, and randomly assigned to two groups (verum and sham transcutaneous
      electrical nerve stimulation [TENS]). First, medic A recorded all baseline
      parameters and measurements, then medic B performed TENS in absence of medic A.
      At the end of transportation, medic A performed data collection. Each patient was
      asked to grade his/her pain and anxiety level on visual analog scales (VAS, 0 to
      100 mm). RESULTS: From 101 screened patients fulfilling the entry criteria, 29
      declined consent and 9 had to be excluded from the analysis because of their
      final diagnosis. Therefore, the data from 30 patients (group 1, verum TENS) as
      well as from 33 patients (group 2 [control], sham TENS) were analyzed. No
      significant differences in potentially influencing factors were found before
      treatment. Pain scores upon arrival at the hospital differed significantly
      between group 1 and group 2 (p < 0.01). In group 1, pain reduction was observed
      between departure from the site of emergency and arrival at the hospital (VAS: 89
      +/- 9 to 59 +/- 6 mm), whereas pain scores remained nearly unchanged in group 2
      (VAS: 86 +/- 12 to 79 +/- 11 mm). CONCLUSION: Our findings show that TENS is a
      valuable and fast-acting pain treatment under the difficult circumstances of "out
      of-hospital rescue". Because of its lack of side effects, it could also be a
      valuable tool in the hospital.

PMID- 17215754
TI  - Effects of serum from rats with combined radiation-burn injury on the growth of
      hematopoietic progenitor cells.
AB  - BACKGROUND: This study aims to observe the effects of blood serum from rats with
      radiation injury, burn injury, and combined radiation-burn injury on the growth
      of hematopoietic progenitor cells and to explore the possible mechanisms.
      METHODS: Serum from rats with radiation injury, burn injury, and combined
      radiation-burn injury were collected at 3 hours, 12 hours, 24 hours, 48 hours, 72
      hours, and 96 hours after injury and then was added to the culture medium to see
      its effect on the growth of hematopoietic progenitor cells (HPCs) at a final
      protein concentration of 10 microg/mL. Radioimmunoassay and enzyme-linked
      immunosorbent assay were employed to measure the level of tumor necrosis factor
      (TNF)-alpha and interleukin (IL)-6 in each group, and the effect of TNF-alpha and
      IL-6 on the growth of HPC was also observed. RESULTS: The number of HPCs colonies
      formed after addition of the serum from rats with burn or combined radiation-burn
      injuries was significantly higher than that from normal rats at 3 hours, 12
      hours, 24 hours, 48 hours, 72 hours, and 96 hours after injury and reached its
      peak value at 24 hours after injury. However, fewer HPCs colonies were found
      after the addition of the serum from irradiated rats. At the same time, the
      levels of TNF-alpha and IL-6 in the serum of burn group and combined radiation
      burn injury group were significantly higher than that of normal group, and much
      higher than that of the irradiation injury group (p < 0.01). Also, TNF-alpha and
      IL-6 demonstrated promoting effect on the growth of HPC. CONCLUSION: Serum from
      rats with burn injury and combined radiation-burn injury stimulates the growth of
      HPCs, while serum from irradiated rats shows inhibitory effects on the growth of
      HPCs. These effects may lie in the different level of TNF-alpha and IL-6 in the
      serum of each group.

PMID- 17215755
TI  - Correlates to traumatic brain injury in nonhuman primates.
AB  - BACKGROUND: Traumatic brain injury (TBI) is a major health problem, both in terms
      of the economic cost to society and the survivor's quality of life. The
      development of devices to protect against TBI requires criteria that relate
      observed injury to measurements of head kinematics. The objective of this study
      is to find the best statistical correlates to impact-induced TBI in nonhuman
      primates using a qualified, self-consistent set of historical kinematic and TBI
      data from impact tests on nonhuman primates. METHODS: A database was constructed
      and qualified from historical head impact tests on nonhuman primates.
      Multivariate logistic regression analysis with backwards stepwise elimination was
      performed. Variables considered are the peak rotational acceleration (Omegamax),
      the peak linear acceleration (Amax), and the number of impacts (N). RESULTS:
      Bivariate combinations of angular acceleration and the number of impacts are the
      best correlates to all modes of TBI considered, i.e., concussion, subarachnoid
      hemorrhage, brain contusion, and subdural hematoma. For a nonhuman primate with
      100-g brain mass, the criteria that the probability of TBI is less than 10% by
      injury mode are:Concussion: OmegamaxN(0.84) < 70 krad/s/s SAH: OmegamaxN(0.70) <
      160 krad/s/s Contusion: Omegamax N(0.35) < 160 krad/s/s SDH: Omegamax N(0.60) <
      280 krad/s/s CONCLUSIONS: Based on this dataset, the best statistically based
      risk factor for all modes of TBI in nonhuman primates is the bivariate
      combination of rotational acceleration and number of impacts.

PMID- 17215756
TI  - Noninvasive measurement of intracranial pressure: is it possible?
AB  - BACKGROUND: Some publications suggest a strong correlation between the
      intracranial pressure and the intraocular pressure. Other studies claim no
      correlation between these two physiologic variables. Our aim was to study whether
      the tonometry could be a useful method to evaluate intracranial pressure in
      patients with suspected intracranial abnormality. METHODS: We evaluated the
      correlation between the intracranial pressure and the intraocular pressure, the
      intracranial pressure and the mean arterial pressure, and the intraocular
      pressure and the mean arterial pressure in 22 patients, initially comatose, who
      were admitted to our hospital. All patients required the intracranial pressure
      monitoring on clinical grounds. Simultaneous measurements were performed and
      recorded. RESULTS: We calculated both the linear correlation coefficient and the
      Spearman rank-order correlation coefficient. We found significant correlation
      between the intraocular pressure and the mean arterial pressure in 12 patients;
      however, significant correlation between the intraocular pressure and the
      intracranial pressure was found in only 2 patients. CONCLUSION: Tonometry is not
      an appropriate method for the assessment of intracranial pressure increases.

PMID- 17215757
TI  - Randomized, controlled investigation of the anti-infective properties of the
      Alexis retractor/protector of incision sites.
AB  - BACKGROUND: We prospectively investigated whether the wound-protective Alexis
      (Applied Medical, Rancho Santa Margarita, CA) wound retractor was effective in
      preventing surgical site infection (SSI). METHODS: We examined the actual
      condition of SSI in a 12-month randomized, controlled trial consisting of 221
      patients who had undergone nontraumatic gastrointestinal surgery. The patients
      were divided into a With Alexis retractor group (n = 111) and a Without Alexis
      retractor group (n = 110). We also analyzed SSI separately on the basis of
      surgical sites such as gastric surgery or colorectal surgery. RESULTS: Overall
      estimation showed a significant decrease in wound infection (superficial
      incisional SSI) in the With Alexis retractor group. In the analysis based on
      surgical sites, a significant decrease in wound infection was noted in the With
      Alexis retractor group, the members of which had undergone colorectal surgery.
      There was no significant difference between the two groups in the occurrence of
      organ/space SSI, including anastomotic leak or intraperitoneal abscess.
      CONCLUSION: It was suggested that the use of the Alexis wound retractor would
      protect surgical wounds from contamination by bacteria and thus prevent
      infection.

PMID- 17215758
TI  - Outcomes of management in stable children with intra-abdominal free fluid without
      solid organ injury after blunt abdominal injury.
AB  - BACKGROUND: The optimal management of hemodynamically stable children without
      solid-organ injury and with intra-abdominal free fluid on computed tomographic
      (CT) scan is highly debatable. The possibility of hollow viscus injury in this
      setting has led many to propose mandatory exploration. We think that stable
      children with intra-abdominal fluid without solid organ injury can be managed
      nonoperatively. METHODS: The charts of all children less than 18 years of age who
      had an abdominopelvic CT scan after a blunt abdominal trauma between January 2001
      and July 2004 were queried. Patient demographics, mechanism of injury, vital
      signs, physical examination, laboratory data, CT findings, and outcomes of
      management were reviewed. RESULTS: There were 37 pediatric patients identified
      during the study period who met the selection criteria. Twenty were boys and 17
      were girls. Thirty-one patients had a small amount of fluid and six had a
      moderate amount of fluid. The most common mechanism of injury was motor vehicle
      crash (MVC). Thirty-one patients were successfully managed nonoperatively. Six
      patients received an exploratory laparotomy. Intraoperative findings included
      mesenteric injuries with or without ischemic bowel. There were no cases of hollow
      viscus perforation. CONCLUSIONS: Nonoperative management of stable patients with
      small amounts of free fluid in the absence of significant abdominal findings is
      appropriate in the pediatric population. Increasing amounts of tenderness
      elicited on physical examination correlates well with the presence of more than a
      small amount of fluid. The presence of seat belt sign and more than a small
      amount of fluid may be associated with an increased likelihood of operative
      intervention.

PMID- 17215759
TI  - Rural motor vehicle crash risk of death is higher after controlling for injury
      severity.
AB  - BACKGROUND: Motor vehicle crash (MVC) mortality rates are inversely related to
      population density. The purpose of this study was to analyze if there is a
      regional variation in the risk of MVC death after controlling for injury
      severity. METHODS: The study utilized the Crash Outcome Data Evaluation System
      (CODES) data set in Nebraska. All fatal or injury-related crashes during a 4-year
      period (1996 through 1999) were analyzed. Injury Severity Scores (ISSs) were
      calculated from the CODES listed International Classification of Diseases
      diagnoses. Logistic regression analysis was performed to analyze the odds ratio
      for death in three rural county groupings compared with urban locations. RESULTS:
      During the 4-year period, 56,727 people were injured and 1,237 were killed in
      38,493 MVCs. Of these, 45,222 (78%) records had complete information on variables
      of interest. In addition, 28,859 (50%) records had enough information to
      calculate an ISS. A total of 22,181 (39%) records had complete information on the
      variables of interest and ISSs. After adjusting for the effects of speed limit,
      age, and alcohol involvement (but not ISS), the odds of death were 1.24 (1.01
      1.53) higher in the large, non-adjacent and 1.38 (1.14-1.66) small, non-adjacent
      rural counties. After adjusting for the effect of ISS, the odds of death were
      1.98 (1.18-3.31) higher in the small, non-adjacent rural counties. CONCLUSION:
      After controlling for ISS, the risk of MVC death is nearly twice as high in the
      most rural counties in Nebraska. This finding suggests that variation in medical
      care may contribute to this regional variation.

PMID- 17215760
TI  - Nonunion of comminuted transverse sternal fracture involving manubrio-sternal
      joint fixed with metal plates and autogenous bone graft.

PMID- 17215761
TI  - Thoracic outlet syndrome resulting from first rib fracture.

PMID- 17215763
TI  - Acute tracheoesophageal burst injury after blunt chest trauma: case report and
      review of the literature.

PMID- 17215764
TI  - Hypopharyngeal rupture secondary to blunt trauma: presentation, evaluation, and
      management.

PMID- 17215762
TI  - Nonoperative management of asymptomatic traumatic pulmonary hernia in a young
      child.

PMID- 17215765
TI  - Bronchofiberoscopic diagnosis of bronchial disruption and pneumonectomy using a
      percutaneous cardio-pulmonary bypass system.

PMID- 17215766
TI  - Pancreatic transection as a complication of the Heimlich maneuver: case report
      and literature review.

PMID- 17215767
TI  - Splenic rupture after colonoscopy: case report and literature review.

PMID- 17215768
TI  - Treatment of medial malleolar fractures using fine-threaded K-wires: a new
      operative technique.

PMID- 17215769
TI  - Traumatic fall injury causing a displaced vertebral body fracture with
      concomitant abdominal aortic injury.

PMID- 17215770
TI  - Blind subxiphoid pericardiotomy (BSP) and emergency physicians performing
      percutaneous catheter drainage (PCD).

PMID- 17215771
TI  - Latin American Consensus Conference on Hepatitis C.

PMID- 17215792
TI  - Reactive oxygen metabolites as an index of chronic obstructive pulmonary disease
      severity.
AB  - AIM: The purpose of this study was to determine whether reactive oxygen
      metabolite species (ROMs) correlated with lung function in patients with chronic
      obstructive pulmonary disease (COPD) and to investigate whether ROMs could be
      used as an index of COPD severity. METHODS: ROMs were evaluated in plasma by a
      colorimetric method (d-ROM-test) in 94 patients with COPD and in 31 healthy
      nonsmokers subjects. Spirometry, exhaled carbon monoxide and pulse oxymetry was
      performed in all patients. RESULTS: Mean plasma ROMs were significantly increased
      (330.38 Carratelli units) in patients with COPD. There was a negative correlation
      of ROMs with forced expiratory volume in the first second (r= -0.275, P<0.007),
      with forced vital capacity (r= -0.278, P<0.007), with forced expiratory flow (r= 
      0.226, P<0.029) and with oxygen saturation (r= -0.315, P<0.010). In addition a
      positive correlation was found between the age of the patients and the oxidative
      stress (r= 0.366, P<0.000). CONCLUSIONS: These data indicate the presence of
      systemic oxidative stress in patients with COPD. The increased oxidative stress
      in COPD patients was concomitant with the impairment of lung function.

PMID- 17215793
TI  - Receptor activator of NF(Kappa)B ligand/osteoprotegerin (RANKL/OPG) system and
      osteopontin (OPN) serum levels in a population of apulian postmenopausal women.
AB  - AIM: Osteoporosis is a bone disease, characterized by a reduction of bone
      resistance; in postmenopausal period bone metabolism is imbalanced. Several
      parameters have been proposed as markers of bone metabolism; the attention have
      been recently placed on the receptor of activator of NF(Kappa)B ligand receptor
      (RANKL) and osteoprotegerin (OPG), namely RANKL/OPG system. The aim of this paper
      is to evaluate changes in postmenopausal women in serum concentration of OPG,
      RANKL, and their ratio (i.e. RANKL/OPG ratio), osteopontin (OPN), bone-type
      alcaline phosphatase (BAP), serum-N-Telopeptide of type I collagen (serum-NTX);
      and their correlations with bone mineral density (BMD). METHODS: An Apulian
      population group of 163 native postmenopausal women were followed at the
      Osteoporosis Centre of Policlinico of Bari (Southenrn Italy). Patients were
      classified into 3 separate groups, according to T-score: osteoporotic, osteopenic
      and control group. Serum concentrations of OPG, RANKL, RANKL/OPG ratio, BAP and
      NTX have been calculated. RESULTS: No differences were found in OPG and BAP
      values. Significant correlations were found in the osteopenic group between OPG
      and RANKL (negative), and between RANKL and OPN or serum-NTX, OPN and serum-NTX
      or RANKL/OPG ratio, BAP and serum-NTX, serum-NTX and RANKL/OPG ratio (positive).
      In the other groups a significant correlation was observed between BAP and NTX.
      CONCLUSIONS: In postmenopausal women, important modifications of bone metabolism
      markers (i.e. RANKL, OPG and OPN) could be due to serious engagement of bone
      turnover, especially in the pre-osteoporotic phase. Low bone density in
      postmenopausal women should be identified as soon as possible, and urgent
      measures are needed to reverse the process. Parameters namely RANKL e OPG may
      become an important index for the evaluation of the activity of drugs against
      osteoporosis, old and new like AMG 162 (anti-RANKL action).

PMID- 17215794
TI  - Chronic obstructive pulmonary disease and sleep: the interaction.
AB  - Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of
      death, affecting 14 millions adults in the United States. Symptoms related to
      sleep disturbances are common in individuals with moderate to severe COPD,
      particularly in the elderly, which is commonly manifested as morning fatigue and
      early awakenings. One major cause of morbidity in this population is
      abnormalities in gas exchange and resultant hypoxemia as they can lead to
      elevated pulmonary pressures, dyspnea and in severe cases right ventricular
      overload and failure. Sleep has profound adverse effects on respiration and gas
      exchange in patients with COPD. There are several mechanisms underlying nonapneic
      oxygen desaturation during sleep. They include decreased functional residual
      capacity, diminished ventilatory responses to hypoxia and hypercapnia, impaired
      respiratory mechanics, diminished arousal, respiratory muscle fatigue, diminished
      nonchemical respiratory drive, increased upper airway resistance, and the
      starting point of baseline saturation values while awake on the oxyhemoglobin
      dissociation curve. Smoking cessation, bronchodilation, inhaled steroids in those
      with a reversible component and pulmonary rehabilitation are corner stones of
      treatment of COPD. The goals of therapy for the clinician should be to improve
      lung mechanics as well as gas exchange ultimately leading to better sleep quality
      and health status.

PMID- 17215795
TI  - Aspiration pneumonia. Pathophysiological aspects, prevention and management. A
      review.
AB  - Aspiration pneumonias occur more frequently than reported and, in many cases, the
      disease is not recognised. In hospitalised and institutionalised patients with
      predisposing diseases prompt diagnosis of this complication and correct
      preventive measures can drastically reduce the worsening of clinical conditions
      and the deaths due to aspiration pneumonia. Normal airway structure, effective
      defence mechanisms, and preventive measures are decisive in reducing aspiration
      episodes. An increased aspiration risk for food, fluids, medications, or
      secretions may lead to the development of pneumonia. Pneumonia is the most common
      respiratory complication in all stroke deaths and in mechanical ventilation
      patients. In addition, the increased incidence of aspiration pneumonia with aging
      may be a consequence of impairment of swallowing and the cough reflex. Dysphagia,
      compromised consciousness, invasive procedures, anaesthesia, insufficient oral
      care, sleep disorders, and vomiting are all risk factors. Aspiration pneumonia
      includes different characteristic syndromes based on the amount (massive, acute,
      chronic) and physical character of the aspirated material (acid, infected,
      lipoid), needing a different therapeutic approach. Chronic patients education and
      correct health care practices are the keys for preventing the events of
      aspiration. In patients at risk a clinical and instrumental assessment of
      dysphagia should be evaluated. Management includes the removal of etiologic
      factors (drugs, tubes, mobilisation, oral hygiene), supportive care, and in
      bacterial pneumonias a specific antibiotic therapy for community-acquired or
      nosocomial events.

PMID- 17215796
TI  - Updated review (2006) on Helicobacter pylori as a potential target for the
      therapy of ischemic heart disease.
AB  - Despite knowledge about the classical risk factors for ischemic heart disease
      (IHD) has increased, all the differences in morbidity as well as mortality from
      this disease cannot be fully explained. Hence the importance of looking for other
      causal mechanisms. Numerous infectious agents have been linked to IHD and among
      these also Helicobacter pylori (H. pylori). However, a number of studies have
      reported conflicting RESULTS: The present review attempts to highlight on the
      update pertaining a potential etiologic role of H. pylori infection in the
      pathogenesis of IHD. Some new evidences have emerged in the last years in
      literature. While epidemiological approach seems to confirm previous
      uncertainties (hypothetical role of the bacterium in the acute phase),
      experiments have demonstrated the presence of bacterial DNA in the plaque.
      Furthermore, the most encouraging evidence of a possible association emerges from
      an intervention small trial showing a significant reduction of coronary events
      after H. pylori eradication. Because IHD is the outcome of a multiciplity of
      factors, many of which with only a limited individual effect, complete
      understanding of causation is difficult. It may be possible to identify some
      factors, such as H. pylori, the effects of which are large enough to be potential
      target for prevention. This is of major public health importance, since the
      eradication of the infection is easy and certainly much less expensive than long
      term treatment for other risk factors. Prospective population-based studies and
      interventional trials, focusing on the advantage of the eradication of H. pylori
      infection on the prevention or the reduction of recurrence in subjects with IHD,
      should be performed in order to provide support of a causal relationship. This
      represents a promising direction for future studies.

PMID- 17215797
TI  - New antithrombotic agents.
AB  - The main clinical indications for anticoagulant agents are treatment and
      prophylaxis of venous and arterial thromboembolism and acute coronary syndromes.
      For decades, two anticoagulants, heparin and warfarin, have been the principal
      drugs available. Dicumaroid agents have serious limitations due to their narrow
      therapeutic range, needing close monitoring. The interaction with food and drugs
      and the numerous interindividual variations result in unstable effects on
      coagulation parameters. On the other side, heparins have an exclusive parenteral
      use and a risk of immunological adverse reactions. Heparin induced
      thrombocytopenia is the most serious complication. The limitations of existing
      oral and parenteral anticoagulant agents have prompted the search for alternative
      anticoagulant drugs. This paper reviews new anticoagulant agents describing their
      pharmacological and clinical properties. It focuses on the target of their
      anticoagulant action inside the coagulation pathway, and analyzes the clinical
      trials providing indications for new clinical anticoagulation strategies. Agents
      currently under study include direct thrombin inhibitors, indirect activated
      factor X inhibitors, and inhibitors of tissue factor and activated factor VII.
      The new anticoagulant agents may demonstrate improvements in effectiveness,
      safety convenience and cost-effectiveness compared with current anticoagulants.

PMID- 17215798
TI  - A serious skin burn in premature infant: a case report.

PMID- 17215799
TI  - Kearns-Sayre syndrome, compensated hypothyroidism and complete atrio-ventricular
      block.

PMID- 17215800
TI  - GIST: patterns related to survival after surgery.

PMID- 17215806
TI  - Off the rails.

PMID- 17215801
TI  - Quantum information: source of triggered entangled photon pairs?
AB  - The realization of an entangled photon source will be of great importance in
      quantum information--for example, for quantum key distribution and quantum
      computation--and Stevenson et al. have described such a source. However, we show
      here that first, their source is not entangled; second, they use inappropriate
      entanglement indicators that rely on assumptions invalidated by their data; and
      third, their source has insignificant entanglement even after simulating
      subtraction of the significant quantity of background noise. We therefore find
      that the standard of proof required for a semiconductor source of triggered
      entangled photon pairs has not been met by Stevenson et al..

PMID- 17215807
TI  - A corporate response to AIDS.

PMID- 17215808
TI  - Competitive stumbling.

PMID- 17215810
TI  - Power shift stymies US science budget.

PMID- 17215811
TI  - Out of bounds.

PMID- 17215813
TI  - Congress and Bush set to clash on stem cells again.

PMID- 17215812
TI  - Indian science is in decline, says prime minister.

PMID- 17215814
TI  - Immigration policy forces researchers out of West Bank.

PMID- 17215820
TI  - AIDS: on the brink.

PMID- 17215817
TI  - Reinventing an industry.

PMID- 17215821
TI  - Quantum games: states of play.

PMID- 17215822
TI  - Readers see red over low-impact graphics.

PMID- 17215823
TI  - Turks fighting back against anti-evolution forces.

PMID- 17215824
TI  - Poaching laws are useless without solid enforcement.

PMID- 17215825
TI  - Hidden subsidies and risks pump up real price of oil.

PMID- 17215830
TI  - Adaptive immunity: care for the community.

PMID- 17215831
TI  - Particle physics: hard-core revelations.

PMID- 17215832
TI  - Developmental biology: marked from the start.

PMID- 17215833
TI  - Evolutionary biology: genetics and bisexuality.

PMID- 17215835
TI  - Oceanography: a marine nitrogen cycle fix?

PMID- 17215837
TI  - Materials science: displaced by radiation.

PMID- 17215836
TI  - Bioinformatics: industrializing neuroscience.

PMID- 17215838
TI  - Spatial coupling of nitrogen inputs and losses in the ocean.
AB  - Nitrogen fixation is crucial for maintaining biological productivity in the
      oceans, because it replaces the biologically available nitrogen that is lost
      through denitrification. But, owing to its temporal and spatial variability, the
      global distribution of marine nitrogen fixation is difficult to determine from
      direct shipboard measurements. This uncertainty limits our understanding of the
      factors that influence nitrogen fixation, which may include iron, nitrogen-to
      phosphorus ratios, and physical conditions such as temperature. Here we determine
      nitrogen fixation rates in the world's oceans through their impact on nitrate and
      phosphate concentrations in surface waters, using an ocean circulation model. Our
      results indicate that nitrogen fixation rates are highest in the Pacific Ocean,
      where water column denitrification rates are high but the rate of atmospheric
      iron deposition is low. We conclude that oceanic nitrogen fixation is closely
      tied to the generation of nitrogen-deficient waters in denitrification zones,
      supporting the view that nitrogen fixation stabilizes the oceanic inventory of
      fixed nitrogen over time.

PMID- 17215839
TI  - Spin correlations in the electron-doped high-transition-temperature
      superconductor Nd2-xCexCuO4+/-delta.
AB  - High-transition-temperature (high-T(c)) superconductivity develops near
      antiferromagnetic phases, and it is possible that magnetic excitations contribute
      to the superconducting pairing mechanism. To assess the role of
      antiferromagnetism, it is essential to understand the doping and temperature
      dependence of the two-dimensional antiferromagnetic spin correlations. The phase
      diagram is asymmetric with respect to electron and hole doping, and for the
      comparatively less-studied electron-doped materials, the antiferromagnetic phase
      extends much further with doping and appears to overlap with the superconducting
      phase. The archetypal electron-doped compound Nd2-xCexCuO4+/-delta (NCCO) shows
      bulk superconductivity above x approximately 0.13 (refs 3, 4), while evidence for
      antiferromagnetic order has been found up to x approximately 0.17 (refs 2, 5, 6).
      Here we report inelastic magnetic neutron-scattering measurements that point to
      the distinct possibility that genuine long-range antiferromagnetism and
      superconductivity do not coexist. The data reveal a magnetic quantum critical
      point where superconductivity first appears, consistent with an exotic quantum
      phase transition between the two phases. We also demonstrate that the pseudogap
      phenomenon in the electron-doped materials, which is associated with pronounced
      charge anomalies, arises from a build-up of spin correlations, in agreement with
      recent theoretical proposals.

PMID- 17215840
TI  - Quantification of actinide alpha-radiation damage in minerals and ceramics.
AB  - There are large amounts of heavy alpha-emitters in nuclear waste and nuclear
      materials inventories stored in various sites around the world. These include
      plutonium and minor actinides such as americium and curium. In preparation for
      geological disposal there is consensus that actinides that have been separated
      from spent nuclear fuel should be immobilized within mineral-based ceramics
      rather than glass because of their superior aqueous durability and lower risk of
      accidental criticality. However, in the long term, the alpha-decay taking place
      in these ceramics will severely disrupt their crystalline structure and reduce
      their durability. A fundamental property in predicting cumulative radiation
      damage is the number of atoms permanently displaced per alpha-decay. At present,
      this number is estimated to be 1,000-2,000 atoms/alpha in zircon. Here we report
      nuclear magnetic resonance, spin-counting experiments that measure close to 5,000
      atoms/alpha in radiation-damaged natural zircons. New radiological nuclear
      magnetic resonance measurements on highly radioactive, 239Pu zircon show damage
      similar to that caused by 238U and 232Th in mineral zircons at the same dose,
      indicating no significant effect of half-life or loading levels (dose rate). On
      the basis of these measurements, the initially crystalline structure of a 10
      weight per cent 239Pu zircon would be amorphous after only 1,400 years in a
      geological repository (desired immobilization timescales are of the order of
      250,000 years). These measurements establish a basis for assessing the long-term
      structural durability of actinide-containing ceramics in terms of an atomistic
      understanding of the fundamental damage event.

PMID- 17215841
TI  - Redox evolution of a degassing magma rising to the surface.
AB  - Volatiles carried by magmas, either dissolved or exsolved, have a fundamental
      effect on a variety of geological phenomena, such as magma dynamics and the
      composition of the Earth's atmosphere. In particular, the redox state of volcanic
      gases emanating at the Earth's surface is widely believed to mirror that of the
      magma source, and is thought to have exerted a first-order control on the secular
      evolution of atmospheric oxygen. Oxygen fugacity (f(O2) estimated from lava or
      related gas chemistry, however, may vary by as much as one log unit, and the
      reason for such differences remains obscure. Here we use a coupled chemical
      physical model of conduit flow to show that the redox state evolution of an
      ascending magma, and thus of its coexisting gas phase, is strongly dependent on
      both the composition and the amount of gas in the reservoir. Magmas with no
      sulphur show a systematic f(O2) increase during ascent, by as much as 2 log
      units. Magmas with sulphur show also a change of redox state during ascent, but
      the direction of change depends on the initial f(O2) in the reservoir. Our
      calculations closely reproduce the H2S/SO2 ratios of volcanic gases observed at
      convergent settings, yet the difference between f(O2) in the reservoir and that
      at the exit of the volcanic conduit may be as much as 1.5 log units. Thus, the
      redox state of erupted magmas is not necessarily a good proxy of the redox state
      of the gases they emit. Our findings may require re-evaluation of models aimed at
      quantifying the role of magmatic volatiles in geological processes.

PMID- 17215842
TI  - Habitat modification alters the structure of tropical host-parasitoid food webs.
AB  - Global conversion of natural habitats to agriculture has led to marked changes in
      species diversity and composition. However, it is less clear how habitat
      modification affects interactions among species. Networks of feeding interactions
      (food webs) describe the underlying structure of ecological communities, and
      might be crucially linked to their stability and function. Here, we analyse 48
      quantitative food webs for cavity-nesting bees, wasps and their parasitoids
      across five tropical habitat types. We found marked changes in food-web structure
      across the modification gradient, despite little variation in species richness.
      The evenness of interaction frequencies declined with habitat modification, with
      most energy flowing along one or a few pathways in intensively managed
      agricultural habitats. In modified habitats there was a higher ratio of
      parasitoid to host species and increased parasitism rates, with implications for
      the important ecosystem services, such as pollination and biological control,
      that are performed by host bees and wasps. The most abundant parasitoid species
      was more specialized in modified habitats, with reduced attack rates on
      alternative hosts. Conventional community descriptors failed to discriminate
      adequately among habitats, indicating that perturbation of the structure and
      function of ecological communities might be overlooked in studies that do not
      document and quantify species interactions. Altered interaction structure
      therefore represents an insidious and functionally important hidden effect of
      habitat modification by humans.

PMID- 17215843
TI  - Light stimulates growth of proteorhodopsin-containing marine Flavobacteria.
AB  - Proteorhodopsins are bacterial light-dependent proton pumps. Their discovery
      within genomic material from uncultivated marine bacterioplankton caused
      considerable excitement because it indicated a potential phototrophic function
      within these organisms, which had previously been considered strictly
      chemotrophic. Subsequent studies established that sequences encoding
      proteorhodopsin are broadly distributed throughout the world's oceans.
      Nevertheless, the role of proteorhodopsins in native marine bacteria is still
      unknown. Here we show, from an analysis of the complete genomes of three marine
      Flavobacteria, that cultivated bacteria in the phylum Bacteroidetes, one of the
      principal components of marine bacterioplankton, contain proteorhodopsin.
      Moreover, growth experiments in both natural and artificial seawater (low in
      labile organic matter, which is typical of the world's oceans) establish that
      exposure to light results in a marked increase in the cell yield of one such
      bacterium (Dokdonia sp. strain MED134) when compared with cells grown in
      darkness. Thus, our results show that the phototrophy conferred by
      proteorhodopsin can provide critical amounts of energy, not only for respiration
      and maintenance but also for active growth of marine bacterioplankton in their
      natural environment.

PMID- 17215844
TI  - Histone arginine methylation regulates pluripotency in the early mouse embryo.
AB  - It has been generally accepted that the mammalian embryo starts its development
      with all cells identical, and only when inside and outside cells form do
      differences between cells first emerge. However, recent findings show that cells
      in the mouse embryo can differ in their developmental fate and potency as early
      as the four-cell stage. These differences depend on the orientation and order of
      the cleavage divisions that generated them. Because epigenetic marks are
      suggested to be involved in sustaining pluripotency, we considered that such
      developmental properties might be achieved through epigenetic mechanisms. Here we
      show that modification of histone H3, through the methylation of specific
      arginine residues, is correlated with cell fate and potency. Levels of H3
      methylation at specific arginine residues are maximal in four-cell blastomeres
      that will contribute to the inner cell mass (ICM) and polar trophectoderm and
      undertake full development when combined together in chimaeras. Arginine
      methylation of H3 is minimal in cells whose progeny contributes more to the mural
      trophectoderm and that show compromised development when combined in chimaeras.
      This suggests that higher levels of H3 arginine methylation predispose
      blastomeres to contribute to the pluripotent cells of the ICM. We confirm this
      prediction by overexpressing the H3-specific arginine methyltransferase CARM1 in
      individual blastomeres and show that this directs their progeny to the ICM and
      results in a dramatic upregulation of Nanog and Sox2. Thus, our results identify
      specific histone modifications as the earliest known epigenetic marker
      contributing to development of ICM and show that manipulation of epigenetic
      information influences cell fate determination.

PMID- 17215846
TI  - Pharmacogenomics-based tailored versus standard therapeutic regimen for
      eradication of H. pylori.
AB  - Helicobacter pylori eradication rates by triple therapy with a proton pump
      inhibitor, amoxicillin, and clarithromycin at standard doses depend on bacterial
      susceptibility to clarithromycin and patient CYP2C19 genotypes. We examined the
      usefulness of a personalized therapy for H. pylori infection based on these
      factors as determined by genetic testing. First, optimal lansoprazole dosing
      schedules that would achieve sufficient acid inhibition to allow H. pylori
      eradication therapy in each of different CYP2C19 genotype groups were determined
      by a 24-h intragastric pH monitoring. Next, 300 H. pylori-positive patients were
      randomly assigned to the standard regimen group (lansoprazole 30 mg twice daily
      (b.i.d.)), clarithromycin 400 mg b.i.d., and amoxicillin 750 mg b.i.d. for 1
      week) or the tailored regimen group based on CYP2C19 status and bacterial
      susceptibility to clarithromycin assessed by genetic testing. Patients with
      failure of eradication underwent the second-line regimen. The per-patient cost
      required for successful eradication was calculated for each of the groups. In the
      first-line therapy, the intention-to-treat eradication rate in the tailored
      regimen group was 96.0% (95% CI=91.5-98.2%, 144/150), significantly higher than
      that in the standard regimen group (70.0%: 95% CI=62.2-77.2%, 105/150) (P<0.001).
      Final costs per successful eradication in the tailored and standard regimen
      groups were $669 and $657, respectively. In conclusion, the pharmacogenomics
      based tailored treatment for H. pylori infection allowed a higher eradication
      rate by the initial treatment without an increase of the final per-patient cost
      for successful eradication. However, the precise cost-effectiveness of this
      strategy remains to be determined.

PMID- 17215845
TI  - Intestinal drug transporter expression and the impact of grapefruit juice in
      humans.
AB  - The goals of this study were to assess the extent of human intestinal drug
      transporter expression, determine the subcellular localization of the drug uptake
      transporter OATP1A2, and then to assess the effect of grapefruit juice
      consumption on OATP1A2 expression relative to cytochrome P450 3A4 and MDR1.
      Expression of drug uptake and efflux transporters was assessed using human
      duodenal biopsy samples. Fexofenadine uptake by different transporters was
      measured in a transporter-transfected cell line. We investigated the influence of
      grapefruit juice on pharmacokinetics of orally administered fexofenadine. The
      effect of grapefruit juice on the expression of intestinal transporters was
      determined using real-time polymerase chain reaction and Western blot analysis.
      In the duodenum of healthy volunteers, an array of CYP enzymes as well as uptake
      and efflux transporters was expressed. Importantly, uptake transporters thought
      to be liver-specific, such as OATP1B1 and 1B3, as well as OATP2B1 and 1A2 were
      expressed in the intestine. However, among OATP transporters, only OATP1A2 was
      capable of fexofenadine uptake when assessed in vitro. OATP1A2 colocalized with
      MDR1 to the brush border domain of enterocytes. Consumption of grapefruit juice
      concomitantly or 2 h before fexofenadine administration was associated with
      reduced oral fexofenadine plasma exposure, whereas intestinal expression of
      either OATP1A2 or MDR1 remained unaffected. In conclusion, an array of drug
      uptake and efflux transporters are expressed in the human intestine. OATP1A2 is
      likely the key intestinal uptake transporter for fexofenadine absorption whose
      inhibition results in the grapefruit juice effect. Although short-term grapefruit
      juice ingestion was associated with reduced fexofenadine availability, OATP1A2 or
      MDR1 expression was unaffected.

PMID- 17215847
TI  - Plasmid-based gene therapy of diabetes mellitus.
AB  - Type I diabetes mellitus (T1D) is due to a loss of immune tolerance to islet
      antigen and thus, there is intense interest in developing therapies that can re
      establish it. Tolerance is maintained by complex mechanisms that include
      inhibitory molecules and several types of regulatory T cells (Tr). A major
      historical question is whether gene therapy can be employed to generate Tr cells.
      This review shows that gene transfer of immunoregulatory molecules can prevent
      T1D and other autoimmune diseases. In our studies, non-viral gene transfer is
      enhanced by in vivo electroporation (EP). This technique can be used to perform
      DNA vaccination against islet cell antigens and when combined with appropriate
      immune ligands results in the generation of Tr cells and protection against T1D.
      In vivo EP can also be applied for non-immune therapy of diabetes. It can be used
      to deliver protein drugs such as glucagon-like peptide 1 (GLP-1), leptin or
      transforming growth factor beta (TGF-beta). These act in T1D or type II diabetes
      (T2D) by restoring glucose homeostasis, promoting islet cell survival and growth
      or improving wound healing and other complications. Furthermore, we show that in
      large animals EP can deliver peptide hormones, such as growth hormone releasing
      hormone (GHRH). We conclude that the non-viral gene therapy and EP represent a
      safe and efficacious approach with clinical potential.

PMID- 17215848
TI  - Effect of valsartan addition to amlodipine on ankle oedema and subcutaneous
      tissue pressure in hypertensive patients.
AB  - The aim of this study was to assess the effect of valsartan addition to
      amlodipine on ankle foot volume (AFV) and pretibial subcutaneous tissue pressure
      (PSTP), two objective measures of ankle oedema. After a 4-week placebo period, 80
      grade 1-2 hypertensive patients (diastolic blood pressure (DBP)>90 mm Hg and <110
      systolic blood pressure (SBP)>140 mm Hg) were randomized to amlodipine 10 mg or
      valsartan 160 mg or amlodipine 10 mg plus valsartan 160 mg for 6 weeks according
      to an open-label, blinded end point, crossover design. At the end of the placebo
      period and of each treatment period, blood pressure, AFV and PSTP were evaluated.
      AFV was measured using the principle of water displacement. PSTP was assessed
      connecting the subcutaneous pretibial interstitial environment with a water
      manometer. Both amlodipine and valsartan monotherapy significantly reduced SBP (
      16.9 and -14.5 mm Hg, respectively, P<0.01 vs baseline), and DBP (-12.9 and -10.2
      mm Hg, respectively, P<0.01 vs baseline) but the reduction was greater with the
      combination (-22.9 mm Hg for SBP, P<0.01 vs monotherapy; -16.8 mm Hg for DBP,
      P<0.01 vs monotherapy). Amlodipine monotherapy significantly increased both AFV
      (+23%, P<0.01 vs baseline) and PSTP (+75.5%, P<0.001 vs baseline) whereas
      valsartan monotherapy did not influence them. As compared to amlodipine alone,
      the combination produced a less marked increase in AFV (+6.8%, P<0.01 vs
      amlodipine) and PSTP (+23.2%, P<0.001 vs amlodipine). Ankle oedema was clinically
      evident in 24 patients with amlodipine and in six patients with the combination.
      These results suggest that angiotensin receptor blockers partially counteract the
      microcirculatory changes responsible for calcium channel blockers induced oedema
      formation.

PMID- 17215849
TI  - Both angiotensinogen M235T and alpha-adducin G460W polymorphisms are associated
      with hypertension in the Japanese population.

PMID- 17215850
TI  - Association of the aldosterone synthase gene C-344T polymorphism with risk
      factors and survival in a post-myocardial infarction cohort.

PMID- 17215851
TI  - Clinical significance of TP53 mutation in myeloma.

PMID- 17215852
TI  - Multidrug resistance-associated protein 1 expression is under the control of the
      phosphoinositide 3 kinase/Akt signal transduction network in human acute
      myelogenous leukemia blasts.
AB  - A high incidence of relapses following induction chemotherapy is a major
      hindrance to patient survival in acute myelogenous leukemia (AML). There is
      strong evidence that activation of the phosphoinositide 3 kinase (PI3K)/Akt
      signaling network plays a significant role in rendering AML blasts drug
      resistant. An important mechanism underlying drug resistance is represented by
      overexpression of membrane drug transporters such as multidrug resistance
      associated protein 1 (MRP1) or 170-kDa P-glycoprotein (P-gp). Here, we present
      evidence that MRP1, but not P-gp, expression is under the control of the PI3K/Akt
      axis in AML blasts. We observed a highly significant correlation between levels
      of phosphorylated Akt and MRP1 expression in AML cells. Furthermore, incubation
      of AML blasts with wortmannin, a PI3K pharmacological inhibitor, resulted in
      lower levels of phosphorylated Akt, downregulated MRP1 expression, and decreased
      Rhodamine 123 extrusion in an in vitro functional dye efflux assay. We also
      demonstrate that wortmannin-dependent PI3K/Akt inhibition upregulated p53 protein
      levels in most AML cases, and this correlated with diminished MRP1 expression and
      enhanced phosphorylation of murine double minute 2 (MDM2). Taken together, these
      data suggest that PI3K/Akt activation may lead to the development of
      chemoresistance in AML blasts through a mechanism involving a p53-dependent
      suppression of MRP1 expression.

PMID- 17215853
TI  - Increased frequencies of CD4(+)CD25(high) T(regs) correlate with disease relapse
      after allogeneic stem cell transplantation for chronic myeloid leukemia.
AB  - The therapeutic efficacy of allogeneic hemopoietic stem cell transplantation
      (SCT) for chronic myeloid leukemia (CML) largely relies on the graft-versus
      leukemia (GvL) effect exerted by donor T cells. CD4(+)CD25(high) regulatory T
      cells (T(regs)) have been shown to downregulate antitumor responses but their
      role on GvL has not been evaluated. We performed a cross-sectional study in which
      we enumerated and characterized CD4(+)CD25(high) T(regs) in the peripheral blood
      of CML patients undergoing allogeneic SCT. We documented higher frequencies of
      T(regs) in patients after transplant as compared to normal controls and newly
      diagnosed patients. The increment was particularly evident in patients who had
      received their SCT 18 months before. In vitro functional studies demonstrated
      that the T(regs) purified from SCT patients exhibited a more potent suppressive
      activity than T(regs) isolated from healthy volunteers. Patients in whom T(regs)
      numbers were higher than controls more than 18 months after SCT showed evidence
      of disease relapse. Although the increment in T(regs) might have an advantageous
      effect on graft rejection in the early phase post-transplant, our data suggest
      that T(regs) exert an inhibitory effect on GvL.

PMID- 17215854
TI  - Treatment of severe refractory autoimmune hemolytic anemia in B-cell chronic
      lymphocytic leukemia with alemtuzumab (humanized CD52 monoclonal antibody).
AB  - Progressive B-cell chronic lymphocytic leukemia (B-CLL) is often complicated by
      autoimmune hemolytic anemia (AIHA), which in some cases may be refractory to
      conventional therapy such as corticosteroids, rituximab and splenectomy. We
      report here on 5 patients (median age 66 years, range 59-69) with advanced B-CLL,
      all of whom developed severe transfusion-dependent AIHA resistant to conventional
      therapy and received subcutaneous (SC) or intravenous (IV) alemtuzumab, a
      humanized monoclonal antibody that targets the CD52 antigen as salvage treatment
      for AIHA. Alemtuzumab was well tolerated with only minor 'first dose' reactions.
      All 5 patients responded with a >or=2.0 g/dl rise in hemoglobin (Hb)
      concentration, in the absence of further transfusions, after a median time of 5
      weeks (range 4-7), and the mean Hb increased from 7.2 g/dl at baseline to 11.9
      g/dl at end of treatment. All patients remained stable, without further AIHA
      episodes, after a median follow-up time of 12 months with a mean Hb of 12.5 g/dl
      (range 12.2-12.9). For patients with severe, refractory CLL-related AIHA, who
      have not previously responded to conventional therapy, alemtuzumab is an
      effective agent.

PMID- 17215855
TI  - FIP1L1-PDGFRA in chronic eosinophilic leukemia and BCR-ABL1 in chronic myeloid
      leukemia affect different leukemic cells.
AB  - We investigated genetically affected leukemic cells in FIP1L1-PDGFRA+ chronic
      eosinophilic leukemia (CEL) and in BCR-ABL1+ chronic myeloid leukemia (CML), two
      myeloproliferative disorders responsive to imatinib. Fluorescence in situ
      hybridization specific for BCR-ABL1 and for FIP1L1-PDGFRA was combined with
      cytomorphology or with lineage-restricted monoclonal antibodies and applied in
      CML and CEL, respectively. In CEL the amount of FIP1L1-PDGFRA+ cells among CD34+
      and CD133+ cells, B and T lymphocytes, and megakaryocytes were within normal
      ranges. Positivity was found in eosinophils, granulo-monocytes and varying
      percentages of erythrocytes. In vitro assays with imatinib showed reduced
      survival of peripheral blood mononuclear cells but no reduction in colony-forming
      unit growth medium (CFU-GM) growth. In CML the BCR-ABL1 fusion gene was detected
      in CD34+/CD133+ cells, granulo-monocytes, eosinophils, erythrocytes,
      megakaryocytes and B-lymphocytes. Growth of both peripheral blood mononuclear
      cells and CFU-GM was inhibited by imatinib. This study provided evidence for
      marked differences in the leukemic masses which are targeted by imatinib in CEL
      or CML, as harboring FIP1L1-PDGFRA or BCR-ABL1.

PMID- 17215856
TI  - Deletion of 11q23 is a highly specific nonrandom secondary genetic abnormality of
      ETV6/RUNX1-rearranged childhood acute lymphoblastic leukemia.

PMID- 17215857
TI  - Levels of soluble HLA-I and beta2M in patients with acute myeloid leukemia and
      advanced myelodysplastic syndrome: association with clinical behavior and outcome
      of induction therapy.
AB  - beta-2 Microglobulin (beta2M), a subunit of human leukocyte antigen-class I (HLA
      I), is well established as a marker of prognosis in various solid tumors and
      hematologic malignancies. The prognostic role of intact free-circulating HLA-I
      (sHLA-I) is less well understood. We compared the clinical relevance of plasma
      levels of sHLA-I and beta2M in patients with acute myeloid leukemia (AML; n=209)
      or advanced myelodysplastic syndrome (MDS; n=98). sHLA-1 and beta2M levels were
      significantly higher in AML and MDS patients than in control subjects, but did
      not differ significantly between the two disease groups. In AML patients,
      multivariate analysis showed both sHLA-1 and beta2-M to be highly predictive of
      complete remission (CR), survival and duration of complete response (CRD). In
      MDS, the predictive value of the two markers differed substantially from one
      another: beta2M was associated with survival, CR and CRD, whereas sHLA-I was not.
      These findings not only establish the role of sHLA-I as a tumor marker in AML but
      also support that MDS is clinically and biologically distinct from AML. sHLA-I
      has been reported to be an immunomodulator inhibiting the cytotoxic effects of T
      lymphocytes, which may offset its predictive value for disease aggressiveness in
      patients with MDS.

PMID- 17215858
TI  - Diagnosis of invasive aspergillosis by tracking Aspergillus-specific T cells in
      hematologic patients with pulmonary infiltrates.

PMID- 17215859
TI  - Association of KIR2DL5B gene with celiac disease supports the susceptibility
      locus on 19q13.4.
AB  - Genome-wide scans have detected linkage to celiac disease (CD) in several genomic
      locations, including 19q13.4. Killer immunoglobulin-like receptor (KIR) genes map
      to the region and encode receptors of natural killer (NK) cells and certain T
      cells that modulate cytolitic activity through interactions with HLA class I
      ligands, participating in the innate immune response. We performed KIR genotyping
      in a group of 70 CD patients of Basque origin and compared gene content, genotype
      and haplotype frequencies to ethnically matched blood-donors. The frequency of
      gene combination KIR2DL5B(+)/KIR2DL5A(-) was significantly higher in the disease
      group, and this result was confirmed in a second group of 343 CD patients and 160
      controls of Spanish origin, suggesting an implication of this 'unexpressed' gene
      with increased susceptibility to CD (combined OR of 3.63 (95% CI: 1.76-7.51;
      P=0.0004)), possibly due to the lack of an efficient inhibitory signal. Our
      results support the role of the KIR gene cluster in celiac disease and replicate
      the CD-susceptibility locus at 19q13.4.

PMID- 17215860
TI  - Interleukin-18 genetics and inflammatory disease susceptibility.
AB  - IL18 was mapped to 11q22.2-22.3 in 1998. Owing to interleukin (IL)-18's important
      and novel role in immunomodulation, the gene itself has been subject to scrutiny,
      with the aim of discovering variants that may impact on disease susceptibility
      and/or progression. Despite being sequenced numerous times in different
      populations, no non-synonymous variants have been found. However, a number of
      polymorphisms within the proximal promoter have been verified that may interfere
      with transcription-factor-binding sites. Much of the subsequent association
      analyses have centred on these variants, but have yielded no consistent results,
      despite numerous different study populations being genotyped. IL18 has recently
      been resequenced in its entirety, enabling the tagging-single-nucleotide
      polymorphism (tSNP) methodology to be adopted. This approach has yielded
      interesting results, with genetic variation being shown to affect protein levels,
      and risk. This review aims to compile and reflect on the association data of
      interest published to date, with a focus on the diseases related to aberrant
      inflammatory control.

PMID- 17215861
TI  - Involvement of macrophage migration inhibitory factor gene in celiac disease
      susceptibility.
AB  - The MIF gene has been associated with several diseases with inflammatory and
      autoimmune background, such as ulcerative colitis, rheumatoid arthritis and
      systemic lupus erythematosus. We aimed at testing the influence of two functional
      MIF promoter variants in celiac disease (CD) susceptibility. A (CAAT)(5-8)
      tetranucleotide repeat at position -794 and a single-nucleotide polymorphism at 
      173G/C were analyzed in the Spanish population (531 patients and 887 healthy
      controls). chi(2) statistics or Fisher exact test were used for comparisons. The 
      173C allele significantly increased risk ((CC+GC) vs GG: odds ratio (OR) (95%
      confidence interval (CI))=1.41 (1.10-1.81); P=0.005), as did carriage of the
      (CAAT)(7) allele (OR (95% CI)=1.36 (1.02-1.82); P=0.03) and of the haplotype
      (CAAT)(7)//-173C (OR (95% CI)=1.33 (1.00-1.76); P=0.04). Our data evidence for
      first time the role of the MIF gene increasing predisposition to CD. A common
      effect of MIF variants seems to underlie the etiology of these complex
      conditions.

PMID- 17215862
TI  - The interleukin-10 gene promoter polymorphism -1087AG does not correlate with
      clinical outcome in non-Hodgkin's lymphoma.
AB  - The Interleukin 10 (IL-10) gene is highly polymorphic, and the IL-10(-1087AG)
      (rs1800896) gene variation is the only so far studied intensively in association
      with certain diseases. Conflicting data have been published about an association
      of IL-10(-1087AG) gene variation with lower rates of complete remission and lower
      overall survival (OS) in patients with diffuse large B-cell lymphoma. To further
      investigate this in malignant lymphoma, we established the IL-10 genotypes in
      patients from the NHL-B1/ B2 studies from the German High-Grade Non-Hodgkin's
      Lymphoma Study Group. In our study, allele frequencies of lymphoma patients are
      comparable as in healthy controls. No increase of IL-10(-1087G) alleles was
      found. In addition we did not find any difference in OS or event-free survival
      between patients with IL-10(-1087AA) and the other genotypes. Comparable results
      were obtained for the IL-10 loci at -3538 (A/T), -1354 (A/G), -824 (C/T) and -597
      (A/C) (rs1800890, rs1800893, rs1800871 and rs1800872).

PMID- 17215863
TI  - Interleukin-1 superfamily genes expression in normal or impaired human
      spermatogenesis.
AB  - Interleukin-1 (IL-1) is a pleiotropic cytokine that may play a role in
      contributing to the specific immune environment of mammalian testis and in
      regulating cell differentiation. We have determined the transcription activity of
      the IL-1 gene family (using real-time polymerase chain reaction (PCR)) in two
      main functional testicular compartments (interstitial and intratubular ones), and
      in tissue homogenates obtained from patients with fertility disorders
      (spermatogenic arrest and testicular tumors). We observed the prominent
      expression of gene coding for IL-1 receptor antagonist (IL-1RA) in a purified
      fraction of gametogenic cells (normal gonad). Caspase-1 (ICE - IL-1beta
      converting enzyme) was highly expressed (on mRNA level) in interstitial
      compartments as well in testicular tumors (immune enhancement?). In addition we
      found, that the activity of IL-1RA gene decreased along spermatogenic alteration
      in an inversely related manner with IL-1alpha (from normal gonad through
      spermatogenic arrest to Sertoli cell only syndrome). Therefore, the quotient
      value of IL-1alpha/IL-1RA could potentially serve as the diagnostic molecular
      probe for spermatogenesis assessment. The precise level of mRNA for IL-1-IL-18
      cytokines and their receptors, and specifically of the receptor antagonist in
      immune privileged gonad, could be one of the main factors responsible for
      maintaining testicular homeostasis, thus enabling generation of the mature
      spermatozoa.

PMID- 17215864
TI  - NO and CO differentially activate soluble guanylyl cyclase via a heme pivot-bend
      mechanism.
AB  - Diatomic ligand discrimination by soluble guanylyl cyclase (sGC) is paramount to
      cardiovascular homeostasis and neuronal signaling. Nitric oxide (NO) stimulates
      sGC activity 200-fold compared with only four-fold by carbon monoxide (CO). The
      molecular details of ligand discrimination and differential response to NO and CO
      are not well understood. These ligands are sensed by the heme domain of sGC,
      which belongs to the heme nitric oxide oxygen (H-NOX) domain family, also
      evolutionarily conserved in prokaryotes. Here we report crystal structures of the
      free, NO-bound, and CO-bound H-NOX domains of a cyanobacterial homolog. These
      structures and complementary mutational analysis in sGC reveal a molecular ruler
      mechanism that allows sGC to favor NO over CO while excluding oxygen, concomitant
      to signaling that exploits differential heme pivoting and heme bending. The heme
      thereby serves as a flexing wedge, allowing the N-terminal subdomain of H-NOX to
      shift concurrent with the transition of the six- to five-coordinated NO-bound
      state upon sGC activation. This transition can be modulated by mutations at sGC
      residues 74 and 145 and corresponding residues in the cyanobacterial H-NOX
      homolog.

PMID- 17215865
TI  - ZAP-70 kinase regulates HIV cell-to-cell spread and virological synapse
      formation.
AB  - HIV efficiently spreads in lymphocytes, likely through virological synapses
      (VSs). These cell-cell junctions share some characteristics with immunological
      synapses, but cellular proteins required for their constitution remain poorly
      characterized. We have examined here the role of ZAP-70, a key kinase regulating
      T-cell activation and immunological synapse formation, in HIV replication. In
      lymphocytes deficient for ZAP-70, or expressing a kinase-dead mutant of the
      protein, HIV replication was strikingly delayed. We have characterized further
      this replication defect. ZAP-70 was dispensable for the early steps of viral
      cycle, from entry to expression of viral proteins. However, in the absence of ZAP
      70, intracellular Gag localization was impaired. ZAP-70 was required in infected
      donor cells for efficient cell-to-cell HIV transmission to recipients and for
      formation of VSs. These results bring novel insights into the links that exist
      between T-cell activation and HIV spread, and suggest that HIV usurps components
      of the immunological synapse machinery to ensure its own spread through cell-to
      cell contacts.

PMID- 17215866
TI  - Recognition of ribosomal protein L11 by the protein trimethyltransferase PrmA.
AB  - Bacterial ribosomal protein L11 is post-translationally trimethylated at multiple
      residues by a single methyltransferase, PrmA. Here, we describe four structures
      of PrmA from the extreme thermophile Thermus thermophilus. Two apo-PrmA
      structures at 1.59 and 2.3 A resolution and a third with bound cofactor S
      adenosyl-L-methionine at 1.75 A each exhibit distinct relative positions of the
      substrate recognition and catalytic domains, revealing how PrmA can position the
      L11 substrate for multiple, consecutive side-chain methylation reactions. The
      fourth structure, the PrmA-L11 enzyme-substrate complex at 2.4 A resolution,
      illustrates the highly specific interaction of the N-terminal domain with its
      substrate and places Lys39 in the PrmA active site. The presence of a unique
      flexible loop in the cofactor-binding site suggests how exchange of AdoMet with
      the reaction product S-adenosyl-L-homocysteine can occur without necessitating
      the dissociation of PrmA from L11. Finally, the mode of interaction of PrmA with
      L11 explains its observed preference for L11 as substrate before its assembly
      into the 50S ribosomal subunit.

PMID- 17215868
TI  - Structural insight into the ESCRT-I/-II link and its role in MVB trafficking.
AB  - ESCRT (endosomal sorting complex required for transport) complexes orchestrate
      efficient sorting of ubiquitinated transmembrane receptors to lysosomes via
      multivesicular bodies (MVBs). Yeast ESCRT-I and ESCRT-II interact directly in
      vitro; however, this association is not detected in yeast cytosol. To gain
      understanding of the molecular mechanisms of this link, we have characterised the
      ESCRT-I/-II supercomplex and determined the crystal structure of its interface.
      The link is formed by the vacuolar protein sorting (Vps)28 C-terminus (ESCRT-I)
      binding with nanomolar affinity to the Vps36-NZF-N zinc-finger domain (ESCRT-II).
      A hydrophobic patch on the Vps28-CT four-helix bundle contacts the hydrophobic
      knuckles of Vps36-NZF-N. Mutation of the ESCRT-I/-II link results in a cargo
      sorting defect in yeast. Interestingly, the two Vps36 NZF domains, NZF-N and NZF
      C, despite having the same core fold, use distinct surfaces to bind ESCRT-I or
      ubiquitinated cargo. We also show that a new component of ESCRT-I, Mvb12
      (YGR206W), engages ESCRT-I directly with nanomolar affinity to form a 1:1:1:1
      heterotetramer. Mvb12 does not affect the affinity of ESCRT-I for ESCRT-II in
      vitro. Our data suggest a complex regulatory mechanism for the ESCRT-I/-II link
      in yeast.

PMID- 17215867
TI  - Dissecting muscle and neuronal disorders in a Drosophila model of muscular
      dystrophy.
AB  - Perturbation in the Dystroglycan (Dg)-Dystrophin (Dys) complex results in
      muscular dystrophies and brain abnormalities in human. Here we report that
      Drosophila is an excellent genetically tractable model to study muscular
      dystrophies and neuronal abnormalities caused by defects in this complex. Using a
      fluorescence polarization assay, we show a high conservation in Dg-Dys
      interaction between human and Drosophila. Genetic and RNAi-induced perturbations
      of Dg and Dys in Drosophila cause cell polarity and muscular dystrophy
      phenotypes: decreased mobility, age-dependent muscle degeneration and defective
      photoreceptor path-finding. Dg and Dys are required in targeting glial cells and
      neurons for correct neuronal migration. Importantly, we now report that Dg
      interacts with insulin receptor and Nck/Dock SH2/SH3-adaptor molecule in
      photoreceptor path-finding. This is the first demonstration of a genetic
      interaction between Dg and InR.

PMID- 17215870
TI  - Investigating membrane protein dynamics in living cells.
AB  - Live cell imaging is a powerful tool for understanding the function and
      regulation of membrane proteins. In this review, we briefly discuss 4
      fluorescence-microscopy-based techniques for studying the transport dynamics of
      membrane proteins: fluorescence-correlation spectroscopy, image-correlation
      spectroscopy, fluorescence recovery after photobleaching, and single-particle and
      (or) molecule tracking. The advantages and limitations of each approach are
      illustrated using recent studies of an ion channel and cell adhesion molecules.

PMID- 17215871
TI  - The role of SLAM family receptors in immune cell signaling.
AB  - The signaling lymphocyte-activating molecule (SLAM) family immunoreceptors are
      expressed in a wide array of immune cells, including both T and B lymphocytes. By
      virtue of their ability to transduce tyrosine phosphorylation signals through the
      so-called ITSM (immunoreceptor tyrosine-based switch motif) sequences, they play
      an important part in regulating both innate and adaptive immune responses. The
      critical role of the SLAM immunoreceptors in mediating normal immune reactions
      was highlighted in recent findings that SAP, a SLAM-associated protein, modulates
      the activities of various immune cells through interactions with different
      members of the SLAM family expressed in these cells. Importantly, mutations or
      deletions of the sap gene in humans result in the X-linked lymphoproliferative
      syndrome. In this review, we summarize current knowledge and survey the latest
      developments in signal transduction events triggered by the activation of SLAM
      family receptors in different cell types.

PMID- 17215869
TI  - Structural insights into the innate immune recognition specificities of L- and H
      ficolins.
AB  - Innate immunity relies critically upon the ability of a few pattern recognition
      molecules to sense molecular markers on pathogens, but little is known about
      these interactions at the atomic level. Human L- and H-ficolins are soluble
      oligomeric defence proteins with lectin-like activity, assembled from collagen
      fibers prolonged by fibrinogen-like recognition domains. The X-ray structures of
      their trimeric recognition domains, alone and in complex with various ligands,
      have been solved to resolutions up to 1.95 and 1.7 A, respectively. Both domains
      have three-lobed structures with clefts separating the distal parts of the
      protomers. Ca(2+) ions are found at sites homologous to those described for
      tachylectin 5A (TL5A), an invertebrate lectin. Outer binding sites (S1)
      homologous to the GlcNAc-binding pocket of TL5A are present in the ficolins but
      show different structures and specificities. In L-ficolin, three additional
      binding sites (S2-S4) surround the cleft. Together, they define an unpredicted
      continuous recognition surface able to sense various acetylated and neutral
      carbohydrate markers in the context of extended polysaccharides such as 1,3-beta
      D-glucan, as found on microbial or apoptotic surfaces.

PMID- 17215872
TI  - Renal nucleoside transporters: physiological and clinical implications.
AB  - Renal handling of physiological and pharmacological nucleosides is a major
      determinant of their plasma levels and tissue availabilities. Additionally, the
      pharmacokinetics and normal tissue toxicities of nucleoside drugs are influenced
      by their handling in the kidney. Renal reabsorption or secretion of nucleosides
      is selective and dependent on integral membrane proteins, termed nucleoside
      transporters (NTs) present in renal epithelia. The 7 known human NTs (hNTs)
      exhibit varying permeant selectivities and are divided into 2 protein families:
      the solute carrier (SLC) 29 (SLC29A1, SLC29A2, SLC29A3, SLC29A4) and SLC28
      (SLC28A1, SLC28A2, SLC28A3) proteins, otherwise known, respectively, as the human
      equilibrative NTs (hENTs, hENT1, hENT2, hENT3, hENT4) and human concentrative NTs
      (hCNTs, hCNT1, hCNT2, hCNT3). The well characterized hENTs (hENT1 and hENT2) are
      bidirectional facilitative diffusion transporters in plasma membranes; hENT3 and
      hENT4 are much less well known, although hENT3, found in lysosomal membranes,
      transports nucleosides and is pH dependent, whereas hENT4-PMAT is a H+-adenosine
      cotransporter as well as a monoamine-organic cation transporter. The 3 hCNTs are
      unidirectional secondary active Na+-nucleoside cotransporters. In renal
      epithelial cells, hCNT1, hCNT2, and hCNT3 at apical membranes, and hENT1 and
      hENT2 at basolateral membranes, apparently work in concert to mediate
      reabsorption of nucleosides from lumen to blood, driven by Na+ gradients.
      Secretion of some physiological nucleosides, therapeutic nucleoside analog drugs,
      and nucleotide metabolites of therapeutic nucleoside and nucleobase drugs likely
      occurs through various xenobiotic transporters in renal epithelia, including
      organic cation transporters, organic anion transporters, multidrug resistance
      related proteins, and multidrug resistance proteins. Mounting evidence suggests
      that hENT1 may have a presence at both apical and basolateral membranes of renal
      epithelia, and thus may participate in both selective secretory and reabsorptive
      fluxes of nucleosides. In this review, the renal handling of nucleosides is
      examined with respect to physiological and clinical implications for the
      regulation of human kidney NTs and adenosine signaling, intracellular nucleoside
      transport, and nephrotoxicities associated with some nucleoside drugs.

PMID- 17215873
TI  - Defects in cytochrome oxidase assembly in humans: lessons from yeast.
AB  - The biogenesis of the inner mitochondrial membrane enzyme cytochrome c oxidase
      (COX) is a complex process that requires the actions of ancillary proteins,
      collectively called assembly factors. Studies with the yeast Saccharomyces
      cerevisiae have provided considerable insight into the COX assembly pathway and
      have proven to be a fruitful model for understanding the molecular bases for
      inherited COX deficiencies in humans. In this review, we focus on critical steps
      in the COX assembly pathway. These processes are conserved from yeast to humans
      and are known to be involved in the etiology of human COX deficiencies. The
      contributions from our studies in yeast suggest that this organism remains an
      excellent model system for delineating the molecular mechanisms underlying COX
      assembly defects in humans. Current progress suggests that a complete picture of
      COX assembly will be achieved in the near future.

PMID- 17215874
TI  - Coupling between apical and paracellular transport processes.
AB  - Transcellular transport affects the paracellular flux through 2 distinct
      mechanisms: by determining the driving force and by altering the permeability of
      the paracellular pathway. Such coordination ensures efficient transepithelial
      transport by preventing the build-up of large electrical and osmotic gradients.
      The regulation of paracellular permeability was originally recognized as
      increased paracellular flux of water and solutes upon the activation of the
      intestinal Na+-coupled glucose uptake. Despite great advances in the molecular
      characterization of the tight junctions that form the structural basis of
      epithelial barrier functions, the mechanisms whereby apical transporters alter
      the paracellular pathways remains unresolved. Recent studies suggest that myosin
      based contractility is central to this coupling. In this minireview, we summarize
      our current knowledge of paracellular permeability, its regulation by
      contractility, and the various signaling events that link apical Na+-glucose
      cotransport to myosin phosphorylation. While the role of myosin phosphorylation
      appears to be universal, the mechanism(s) whereby apical transport triggers this
      process is likely cell specific. The current model suggests that in intestinal
      cells, a key factor is a p38 MAP kinase-induced Na+/H+-exchanger-mediated
      alkalinization. We propose an alternative, nonexclusive mechanism in kidney
      tubular cells, in which the key event may be a Na+-cotransport-triggered plasma
      membrane depolarization, which in turn leads to Rho-mediated myosin
      phosphorylation.

PMID- 17215876
TI  - VirB8: a conserved type IV secretion system assembly factor and drug target.
AB  - Type IV secretion systems are used by many gram-negative bacteria for the
      translocation of macromolecules (proteins, DNA, or DNA-protein complexes) across
      the cell envelope. Among them are many pathogens for which type IV secretion
      systems are essential virulence factors. Type IV secretion systems comprise 8-12
      conserved proteins, which assemble into a complex spanning the inner and the
      outer membrane, and many assemble extracellular appendages, such as pili, which
      initiate contact with host and recipient cells followed by substrate
      translocation. VirB8 is an essential assembly factor for all type IV secretion
      systems. Biochemical, cell biological, genetic, and yeast two-hybrid analyses
      showed that VirB8 undergoes multiple interactions with other type IV secretion
      system components and that it directs polar assembly of the membrane-spanning
      complex in the model organism Agrobacterium tumefaciens. The availability of the
      VirB8 X-ray structure has enabled a detailed structure-function analysis, which
      identified sites for the binding of VirB4 and VirB10 and for self-interaction.
      Due to its multiple interactions, VirB8 is an excellent model for the analysis of
      assembly factors of multiprotein complexes. In addition, VirB8 is a possible
      target for drugs that target its protein-protein interactions, which would disarm
      bacteria by depriving them of their essential virulence functions.

PMID- 17215875
TI  - ERp57 and PDI: multifunctional protein disulfide isomerases with similar domain
      architectures but differing substrate-partner associations.
AB  - Secretory proteins become folded and acquire stabilizing disulfide bonds in the
      endoplasmic reticulum (ER). Correct disulfide bond formation is a key step in ER
      quality control (ERQC). Proteins with incorrect disulfide bonds are recognized by
      the quality control machinery and are retrotranslocated into the cytosol where
      they are degraded by the proteasome. The mammalian ER contains 17 disulfide
      isomerases and at least one of them, ERp57, works in conjunction with the ER
      lectin-like chaperones calnexin and calreticulin. The targeting of ERp57 to
      calnexin-calreticulin is mediated by its noncatalytic b' domain, and analogous
      domains in other disulfide isomerases likely determine their substrate and
      partner preferences. This review discusses some explanations for the multiplicity
      of disulfide isomerases and highlights structural differences in the b' domains
      of PDI and ERp57 as an example of how noncatalytic domains define specialized
      roles in oxidative folding.

PMID- 17215877
TI  - Computer simulations of ABC transporter components.
AB  - Current computer simulation techniques provide robust tools for studying the
      detailed structure and functional dynamics of proteins, as well as their
      interaction with each other and with other biomolecules. In this minireview, we
      provide an illustration of recent progress and future challenges in computer
      modeling by discussing computational studies of ATP-binding cassette (ABC)
      transporters. ABC transporters have multiple components that work in a well
      coordinated fashion to enable active transport across membranes. The mechanism by
      which members of this superfamily execute transport remains largely unknown.
      Molecular dynamics simulations initiated from high-resolution crystal structures
      of several ABC transporters have proven to be useful in the investigation of the
      nature of conformational coupling events that may drive transport. In addition,
      fruitful efforts have been made to predict unknown structures of medically
      relevant ABC transporters, such as P-glycoprotein, using homology-based
      computational methods. The various techniques described here are also applicable
      to gaining an atomically detailed understanding of the functional mechanisms of
      proteins in general.

PMID- 17215878
TI  - Hypothesis: Huntingtin may function in membrane association and vesicular
      trafficking.
AB  - Huntington's disease is a progressive neurodegenerative genetic disorder that is
      caused by a CAG triplet-repeat expansion in the first exon of the IT15 gene. This
      CAG expansion results in polyglutamine expansion in the 350 kDa huntingtin
      protein. The exact function of huntingtin is unknown. Understanding the
      pathological triggers of mutant huntingtin, and distinguishing the cause of
      disease from downstream effects, is critical to designing therapeutic strategies
      and defining long- and short-term goals of therapy. Many studies that have sought
      to determine the functions of huntingtin by determining huntingtin's protein
      protein interactions have been published. Through these studies, huntingtin has
      been seen to interact with a large number of proteins, and is likely a
      scaffolding protein for protein-protein interactions. Recently, using imaging,
      integrative proteomics, and cell biology, huntingtin has been defined as a
      membrane-associated protein, with activities related to axonal trafficking of
      vesicles and mitochondria. These functions have also been attributed to some
      huntingtin-interacting proteins. Additionally, discoveries of a membrane
      association domain and a palmitoylation site in huntingtin reinforce the fact
      that huntingtin is membrane associated. In Huntington's disease mouse and fly
      models, axonal vesicle trafficking is inhibited, and lack of proper uptake of
      neurotrophic factors may be an important pathological trigger leading to striatal
      cell death in Huntington's disease. Here we discuss recent advances from many
      independent groups and methodologies that are starting to resolve the elusive
      function of huntingtin in vesicle transport, and evidence that suggests that
      huntingtin may be directly involved in membrane interactions.

PMID- 17215879
TI  - Strategies for dealing with conformational sampling in structural calculations of
      flexible or kinked transmembrane peptides.
AB  - Peptides corresponding to transmembrane (TM) segments from membrane proteins
      provide a potential route for the determination of membrane protein structure. We
      have determined that 2 functionally critical TM segments from the mammalian
      Na+/H+ exchanger display well converged structure in regions separated by break
      points. The flexibility of these break points results in conformational sampling
      in solution. A brief review of available NMR structures of helical membrane
      proteins demonstrates that there are a number of published structures showing
      similar properties. Such flexibility is likely indicative of kinks in the full
      length protein. This minireview focuses on methods and protocols for NMR
      structure calculation and analysis of peptide structures under conditions of
      conformational sampling. The methods outlined allow the identification and
      analysis of structured peptides containing break points owing to conformational
      sampling and the differentiation between oligomerization and ensemble-averaged
      observation of multiple peptide conformations.

PMID- 17215880
TI  - Why bicarbonate?
AB  - Bicarbonate is a simple single carbon molecule that plays surprisingly important
      roles in diverse biological processes. Among these are photosynthesis, the Krebs
      cycle, whole-body and cellular pH regulation, and volume regulation. Since
      bicarbonate is charged it is not permeable to lipid bilayers. Mammalian membranes
      thus contain bicarbonate transport proteins to facilitate the specific
      transmembrane movement of HCO3(-). This review provides a wide-ranging view of
      the biochemistry of bicarbonate and its membrane transporters, revealing what
      makes the study of bicarbonate transport such a rewarding activity.

PMID- 17215881
TI  - PRAF1: a Golgi complex transmembrane protein that interacts with viruses.
AB  - Prenylated Rab acceptor domain family member 1 (PRAF1), a transmembrane protein
      whose precise function is unknown, localizes to the Golgi complex, post-Golgi
      vesicles, lipid rafts, endosomes, and the plasma membrane. VAMP2 and Rab3A are
      SNARE proteins that interact with PRAF1, and, as part of a SNARE complex, PRAF1
      may function in the regulation of docking and fusion of transport vesicles both
      in the Golgi complex and at the plasma membrane. Alternately, PRAF1 may function
      as a sorting protein in the Golgi complex. In addition to interacting with SNARE
      proteins, PRAF1 interacts with rotaviral, retroviral, and herpes viral proteins.
      The function of viral protein interaction is unknown, but PRAF1 may enhance
      rotaviral and retroviral assembly. In contrast, PRAF1 may inhibit the herpes
      virus life cycle.

PMID- 17215882
TI  - Unraveling trafficking of the kidney anion exchanger 1 in polarized MDCK
      epithelial cells.
AB  - Kidney anion exchanger 1 (kAE1) is a membrane glycoprotein expressed at the
      basolateral membrane of type A intercalated cells in the kidney collecting
      tubule. Mutations occurring in the gene encoding this protein can give rise to
      distal renal tubular acidosis (dRTA), a disease characterized by an impaired
      urine acidification, nephrocalcinosis, and renal failure. Here we review how the
      study of dRTA mutants in polarized epithelial cells has shed light on the
      cellular mechanisms resulting in this renal disease.

PMID- 17215883
TI  - Recent progress in structure-function analyses of Nramp proton-dependent metal
      ion transporters.
AB  - The natural resistance-associated macrophage protein (Nramp) homologs form a
      family of proton-coupled transporters that facilitate the cellular absorption of
      divalent metal ions (Me2+, including Mn2+, Fe2+, Co2+, and Cd2+). The Nramp, or
      solute carrier 11 (SLC11), family is conserved in eukaryotes and bacteria. Humans
      and rodents express 2 parologous genes that are associated with iron disorders
      and immune diseases. The NRAMP1 (SLC11A1) protein is specific to professional
      phagocytes and extrudes Me2+ from the phagosome to defend against ingested
      microbes; polymorphisms in the NRAMP1 gene are associated with various immune
      diseases. Several isoforms of NRAMP2 (SLC11A2, DMT1, DCT1) are expressed
      ubiquitously in recycling endosomes or specifically at the apical membrane of
      epithelial cells in intestine and kidneys, and can contribute to iron overload,
      whereas mutations impairing NRAMP2 function cause a form of congenital microcytic
      hypochromic anemia. Structure-function studies, using various experimental
      models, and mutagenesis approaches have begun to reveal the overall transmembrane
      organization of Nramp, some of the transmembrane segments (TMS) that are
      functionally important, and an unusual mechanism coupling Me2+ and proton H+
      transport. The approaches used include functional complementation of yeast
      knockout strains, electrophysiology analyses in Xenopus oocytes, and transport
      assays that use mammalian and bacterial cells and direct and indirect
      measurements of SLC11 transporter properties. These complementary studies enabled
      the identification of TMS1 and 6 as crucial structural segments for Me2+ and H+
      symport, and will help develop a deeper understanding of the Nramp transport
      mechanism and its contribution to Me2+ homeostasis in human health and diseases.

PMID- 17215884
TI  - Shedding light on drug transport: structure and function of the P-glycoprotein
      multidrug transporter (ABCB1).
AB  - P-glycoprotein (Pgp; ABCB1), a member of the ATP-binding cassette (ABC)
      superfamily, exports structurally diverse hydrophobic compounds from the cell,
      driven by ATP hydrolysis. Pgp expression has been linked to the efflux of
      chemotherapeutic drugs in human cancers, leading to multidrug resistance (MDR).
      The protein also plays an important physiological role in limiting drug uptake in
      the gut and entry into the brain. Substrates partition into the lipid bilayer
      before interacting with Pgp, which has been proposed to function as a hydrophobic
      vacuum cleaner. Low- and medium-resolution structural models of Pgp suggest that
      the 2 nucleotide-binding domains are closely associated to form a nucleotide
      sandwich dimer. Pgp is an outwardly directed flippase for fluorescent
      phospholipid and glycosphingolipid derivatives, which suggests that it may also
      translocate drug molecules from the inner to the outer membrane leaflet. The
      ATPase catalytic cycle of the protein is thought to proceed via an alternating
      site mechanism, although the details are not understood. The lipid bilayer plays
      an important role in Pgp function, and may regulate both the binding and
      transport of drugs. This review focuses on the structure and function of Pgp, and
      highlights the importance of fluorescence spectroscopic techniques in exploring
      the molecular details of this enigmatic transporter.

PMID- 17215885
TI  - Partitioning of myelin basic protein into membrane microdomains in a
      spontaneously demyelinating mouse model for multiple sclerosis.
AB  - We have characterized the lipid rafts in myelin from a spontaneously
      demyelinating mouse line (ND4), and from control mice (CD1 background), as a
      function of age and severity of disease. Myelin was isolated from the brains of
      CD1 and ND4 mice at various ages, and cold lysed with 1.5% CHAPS (3-[(3
      cholamidopropyl) dimethylammonio]-1-propanesulphonate). The lysate was separated
      by low-speed centrifugation into supernatant and pellet fractions, which were
      characterized by Western blotting for myelin basic protein (MBP) isoforms and
      their post-translationally modified variants. We found that, with maturation and
      with disease progression, there was a specific redistribution of the 14-21.5 kDa
      MBP isoforms (classic exon-II-containing vs exon-II-lacking) and phosphorylated
      forms into the supernatant and pellet. Further fractionation of the supernatant
      to yield detergent-resistant membranes (DRMs), representing coalesced lipid
      rafts, showed these to be highly enriched in exon-II-lacking MBP isoforms, and
      deficient in methylated MBP variants, in mice of both genotypes. The DRMs from
      the ND4 mice appeared to be enriched in MBP phosphorylated by MAP kinase at Thr95
      (murine 18.5 kDa numbering). These studies indicate that different splice
      isoforms and post-translationally modified charge variants of MBP are targeted to
      different microdomains in the myelin membrane, implying multifunctionality of
      this protein family in myelin maintenance.

PMID- 17215886
TI  - The position of the Gly-xxx-Gly motif in transmembrane segments modulates dimer
      affinity.
AB  - Although the intrinsic low solubility of membrane proteins presents challenges to
      their high-resolution structure determination, insight into the amino acid
      sequence features and forces that stabilize their folds has been provided through
      study of sequence-dependent helix-helix interactions between single transmembrane
      (TM) helices. While the stability of helix-helix partnerships mediated by the Gly
      xxx-Gly (GG4) motif is known to be generally modulated by distal interfacial
      residues, it has not been established whether the position of this motif, with
      respect to the ends of a given TM segment, affects dimer affinity. Here we
      examine the relationship between motif position and affinity in the homodimers of
      2 single-spanning membrane protein TM sequences: glycophorin A (GpA) and
      bacteriophage M13 coat protein (MCP). Using the TOXCAT assay for dimer affinity
      on a series of GpA and MCP TM segments that have been modified with either 4 Leu
      residues at each end or with 8 Leu residues at the N-terminal end, we show that
      in each protein, centrally located GG4 motifs are capable of stronger helix-helix
      interactions than those proximal to TM helix ends, even when surrounding
      interfacial residues are maintained. The relative importance of GG4 motifs in
      stabilizing helix-helix interactions therefore must be considered not only in its
      specific residue context but also in terms of the location of the interactive
      surface relative to the N and C termini of alpha-helical TM segments.

PMID- 17215888
TI  - P-glycoprotein (ABCB1) interacts directly with lipid-based anti-cancer drugs and
      platelet-activating factors.
AB  - The P-glycoprotein multidrug transporter (Pgp; ABCB1) is an ATP-binding cassette
      (ABC) protein that has been implicated in the multidrug resistance of human
      cancers. Pgp couples ATP hydrolysis to active extrusion from the cell of a broad
      array of amphipathic compounds via an ill-defined mechanism. Substrates are
      believed to interact with Pgp within the membrane. Reconstituted Pgp functions as
      an ATP-dependent flippase for a variety of fluorescently labelled membrane
      lipids. The protein may also function as a drug 'flippase', moving its substrates
      from the inner to the outer leaflet of the bilayer. We show that lipid-based anti
      cancer drugs, such as miltefosine, and signaling molecules, such as platelet
      activating factors, bind saturably to Pgp with Kd values in the low micromolar
      range, and modulate its ATPase activity. These compounds also inhibit Pgp
      mediated flipping of fluorescent lipids and transport of Hoechst 33342 and
      tetramethylrosamine, which occupy different subsites in the drug-binding pocket.
      Bacterial lipid A modulates Pgp ATPase activity, and glycolipid flipping is
      inhibited by unlabelled glucosylceramide, suggesting that these lipids also
      interact with the transporter. These results indicate that Pgp treats a variety
      of lipid-based molecules as substrates, and likely interacts with lipids and
      drugs in the same manner.

PMID- 17215889
TI  - K-Cl cotransport in red blood cells from patients with KCC3 isoform mutants.
AB  - Red blood cells (RBCs) possess the K-Cl cotransport (KCC) isoforms 1, 3, and 4.
      Mutations within a given isoform may affect overall KCC activity. In a double
      blind study, we analyzed, with Rb as a K congener, K fluxes (total flux, ouabain
      sensitive Na+/K+ pump, and bumetanide-sensitive Na-K-2Cl cotransport, Cl
      dependent, and ouabain- and bumetanide-insensitive KCC with or without
      stimulation by N-ethylmaleimide (NEM) and staurosporine or Mg removal, and basal
      channel-mediated fluxes, osmotic fragility, and ions and water in the RBCs of 8
      controls, and of 8 patients with hereditary motor and sensory neuropathy with
      agenesis of corpus callosum (HMSN-ACC) with defined KCC3 mutations (813FsX813 and
      Phe529FsX532) involving the truncations of 338 and 619 C-terminal amino acids,
      respectively. Water and ion content and, with one exception, mean osmotic
      fragility, as well as K fluxes without stimulating agents, were similar in
      controls and HMSN-ACC RBCs. However, the NEM-stimulated KCC was reduced 5-fold (p
      < 0.0005) in HMSN-ACC vs control RBCs, as a result of a lower Vmax (p < 0.05)
      rather than a lower Km (p = 0.109), accompanied by corresponding differences in
      Cl activation. Low intracellular Mg activated KCC in 6 out of 7 controls vs 1 out
      of 6 HMSN-ACC RBCs, suggesting that regulation is compromised. The lack of
      differences in staurosporine-activated KCC indicates different action mechanisms.
      Thus, in HMSN-ACC patients with KCC3 mutants, RBC KCC activity, although
      indistinguishable from that of the control group, responded differently to
      biochemical stressors, such as thiol alkylation or Mg removal, thereby indirectly
      indicating an important contribution of KCC3 to overall KCC function and
      regulation.

PMID- 17215887
TI  - Effects of site-directed mutations in Escherichia coli succinate dehydrogenase on
      the enzyme activity and production of superoxide radicals.
AB  - Escherichia coli succinate dehydrogenase (SdhCDAB) catalyzes the oxidation of
      succinate to fumarate in the Krebs cycle, and during turnover, it produces
      superoxide radicals. SdhCDAB is a good model system for the succinate
      dehydrogenase (Sdh) found in the mitochondrial respiratory chain (complex II), as
      the subunits are structural homologues. Although mutations in sdh genes are
      reportedly associated with a variety of mitochondria-related diseases, the
      molecular mechanism of these diseases is poorly understood. We have investigated
      the effects of site-directed mutations around the heme (SdhD-H71L and SdhC-H91L),
      and at the ubiquinone-binding site (Q site; SdhC-I28E), on enzyme activity and
      production of superoxide radicals. The mutations SdhD-H71L and SdhC-I28E, but not
      SdhC-H91L, significantly reduce the succinate-ubiquinone reductase activity of
      the enzyme. All 3 mutant enzymes produce more superoxide than the wild-type
      enzyme, indicating that disturbance of the heme or the Q site can enhance
      superoxide production. The presence of a Q-site inhibitor reduces superoxide
      production significantly. Furthermore, the yield of superoxide is substrate
      dependent and increases with succinate concentration from 0.1 to 10 mmol/L. Our
      results indicate that, in SdhCDAB, the Q site with bound ubiquinone is an
      important source of superoxide radicals.

PMID- 17215890
TI  - Stimulatory effect of insecticides on partially purified P-glycoprotein ATPase
      from the resistant pest Helicoverpa armigera.
AB  - A P-glycoprotein-like protein (Ha-Pgp) was detected in a membrane preparation
      from the insecticide-resistant pest Helicoverpa armigera (Lepidoptera: Noctuidae)
      using C219 antibodies that are directed towards an epitope in the nucleotide
      binding domains. This protein was partially purified and found to be a
      glycoprotein displaying ATPase activity. SDS-PAGE confirmed that a high molecular
      mass glycoprotein (150 kDa) was overexpressed in resistant pests, but was not
      detected in susceptible pests. The partially purified Ha-Pgp ATPase was
      reconstituted into proteoliposomes and it was found that some insecticides,
      namely, monocrotophos, endosulfan, cypermethrin, fenvalerate, and
      methylparathion, stimulated the ATPase activity. The effect of various inhibitors
      on partially purified Ha-Pgp showed that orthovanadate is a potent inhibitor of
      its ATPase activity, inhibiting it by 90% at a concentration of 2 mmol/L. Other
      inhibitors, such as EDTA, sodium azide, and molybdate resulted in only a 20%
      decrease in activity. Details of the structure and function of Ha-Pgp will be
      important in the development of strategies to overcome insecticide resistance in
      this pest.

PMID- 17215891
TI  - Proceedings and abstracts of the 49th Annual Canadian Society of Biochemistry and
      Molecular and Cellular Biology (CSBMCB) Meeting, 2006.

PMID- 17215892
TI  - Use of microbial antagonism to reduce pathogen levels on produce and meat
      products: a review.
AB  - Lactic acid bacteria (LAB) are often utilized to control food-borne pathogens on
      produce and on cooked, fermented, or refrigerated meats. Most research to date
      has focused on the inhibition of Listeria monocytogenes, Escherichia coli
      O157:H7, Salmonella, Clostridium botulinum, and spoilage microorganisms. LAB are
      excellent candidates for reducing pathogen levels on foods because they inhibit
      the growth of these microorganisms through various mechanisms without causing
      unacceptable sensory changes. This review provides an up-to-date look at research
      directed at maximizing the use of LAB by selecting the most appropriate strains,
      by learning how to apply them to foods most effectively, and by gaining an
      understanding of the mechanism by which they inhibit pathogens.

PMID- 17215894
TI  - Chilling and cultivar type affect the diversity of bacterial endophytes
      colonizing sweet pepper (Capsicum anuum L.).
AB  - A climate chamber experiment was conducted to assay the effect of low
      temperatures (chilling) on the diversity of bacteria colonizing the endospheres
      of two thermophilic sweet pepper (Capsicum anuum L.) cultivars, Milder Spiral and
      Ziegenhorn Bello. Structural diversity was analyzed by 16S rRNA-based terminal
      restriction fragment length polymorphism (T-RFLP) analysis and by the generation
      of 16S rRNA gene libraries to determine dominant community members in T-RFLP
      profiles. Cultivable community members colonizing lines Milder Spiral and
      Ziegenhorn Bello were identified by 16S rRNA gene analysis. T-RFLP profiles and
      16S rRNA gene libraries revealed a high heterogeneity of community composition
      due to chilling and suggested further the existence of cultivar-specific
      communities. The majority of isolates obtained from the cultivar Milder Spiral
      were assigned as high-G+C Gram-positive bacteria (Microbacterium sp., Micrococcus
      sp., Rhodococcus sp.) and Firmicutes (Staphylococcus sp.). Of the isolated
      endophytes obtained from cultivar Zeigenhorn Bello, 93% were affiliated with
      Staphylococcus aureus and Bacillus sp. (Firmicutes). The experimental set-up was
      suited to demonstrate that chilling and cultivar type can influence the diversity
      of bacterial endophytes colonizing sweet pepper. We propose additional chilling
      experiments to investigate the effect of chilling on functional, plant-beneficial
      abilities of bacterial endophytes associated with low-temperature-sensitive
      crops, such as sweet pepper.

PMID- 17215893
TI  - A mutation in an exbD gene reduces tagetitoxin production by Pseudomonas syringae
      pv. tagetis.
AB  - A mutant of Pseudomonas syringae pv. tagetis EB037 with limited ability to
      produce tagetitoxin was isolated after transposon mutagenesis and the mutation
      was characterized. The mutation occurred in a gene with a high degree of sequence
      identity to exbD. exbD is contiguous with tonB and exbB upstream and with a gene
      for a TonB-dependent receptor downstream. Using reverse transcription -
      polymerase chain reaction with RNA from the wild-type and exbD mutant strains, we
      demonstrated that the mutation in exbD did not have a polar affect on the
      expression of downstream genes. The exbD mutant was able to grow well in
      conditions where iron is not freely available. Siderophore production by the exbD
      mutant was similar to that of the wild-type strain. We conclude that the mutation
      in exbD disrupts tagetitoxin production without compromising iron metabolism. The
      results indicate that tagetitoxin export by P. syringae pv. tagetis involves an
      efflux pump that requires a functional TonB system that is not essential for
      normal iron metabolism.

PMID- 17215895
TI  - Oxylipin-coated hat-shaped ascospores of Ascoidea corymbosa.
AB  - We previously implicated 3-hydroxy oxylipins and ascospore structure in ascospore
      release from enclosed asci. Using confocal laser scanning microscopy on cells
      stained with fluorescein-coupled, 3-hydroxy oxylipin-specific antibodies, we
      found that oxylipins are specifically associated with ascospores and not the
      vegetative cells or ascus wall of Ascoidea corymbosa. Using gas chromatography-
      mass spectrometry the oxylipin 3-hydroxy 17:0 could be identified. Here, we
      visualize for the first time the forced release of oxylipin-coated, hat-shaped
      ascospores from terminally torn asci, probably through turgor pressure. We
      suggest that oxylipin-coated, razor-sharp, hat-shaped ascospore brims may play a
      role in rupturing the ascus to affect release.

PMID- 17215896
TI  - Detection and sequence analysis of an altered pectate lyase gene in Pseudomonas
      syringae pv. glycinea and related bacteria.
AB  - Pectate lyase (PL) is a potent cell wall-degrading enzyme known to play a role in
      the microbial infection of plants. We re-examined the pectolytic property of
      seven representative pathovars of Pseudomonas syringae. None of the 10 P.
      syringae pv. glycinea strains examined exhibited pectolytic activity. However,
      the PL gene (pel) was detected by Southern hybridization in four out of four P.
      syringae pv. glycinea strains examined. A P. syringae pv. glycinea pel gene was
      cloned, sequenced, and predicted to encode a protein sharing 70%-90% identity in
      amino acid sequence with PLs produced by pectolytic pseudomonads and
      xanthomonads. A series of amino acid and nucleotide sequence analyses reveal that
      (i) the predicted P. syringae pv. glycinea PL contains two regions in the amino
      acid sequence that may affect the formation of a beta-helix structure important
      for the enzyme activity, and (ii) the P. syringae pv. glycinea pel gene contains
      a single-base insertion, a double-base insertion, and an 18-bp deletion, which
      can lead to the synthesis of an inactive PL protein. The function of P. syringae
      pv. glycinea PL could be restored by removing the unwanted base insertions and by
      filling in the 18-bp deletions by site-directed mutagenesis. The altered pel
      sequence was also detected by polymerase chain reaction and nucleotide sequencing
      in the genomes of other pathovars of P. syringae, including phaseolicola and
      tagetis.

PMID- 17215897
TI  - Secretion of keratinolytic enzymes and keratinolysis by Scopulariopsis
      brevicaulis and Trichophyton mentagrophytes: regression analysis.
AB  - A survey on keratinophilic fungi from poultry-farm soils at Namakkal and from
      feather dumping soils at Chennai, India, revealed the existence of 34 species of
      fungi. Most of the fungi exhibited variable efficiency in producing extracellular
      keratinase when grown in plates with chicken feathers as the sole carbon and
      nitrogen source. The fungi Aspergillus flavus, Aspergillus niger, Aspergillus
      versicolor, Chrysosporium state of Arthroderma tuberculatum, Paecilomyces
      carneus, Scopulariopsis brevicaulis, Trichoderma viride, and Trichophyton
      mentagrophytes were efficient candidates to degrade the feathers. However, when
      cultivating the strains in submerged conditions in a medium containing chicken
      feathers as the sole nutrients source, Aspergillus glaucus, Chrysosporium
      keratinophilum, Curvularia lunata, Fusarium solani, and Penicillium citrinum also
      proved to be potent. Among all species, S. brevicaulis and Trichophyton
      mentagrophytes produced higher amounts of keratinase in both methods. Conditions
      for keratinase production were optimized by statistical design and surface plots.
      The highest keratinase activity was estimated by S. brevicaulis (3.2 KU/mL) and
      Trichophyton mentagrophytes (2.7 KU/mL) in the culture medium with chicken
      feathers and shows (79% and 72.2% of degrading ability, respectively).

PMID- 17215898
TI  - Molecular characterization and expression profile of pectin-lyase-encoding genes
      from Penicillium griseoroseum.
AB  - Penicillium griseoroseum has been studied by our group because of its good
      pectinase production. Attempts have been done to clone pectinolytic genes, aiming
      to obtain pectinase-overproducing strains for industrial purposes. Here, two
      genes coding for pectin lyase were isolated from the P. griseoroseum genome. The
      plg1 gene has an open reading frame of 1341 bp coding for a putative protein of
      374 amino acids with a calculated molecular mass of 40.1 kDa. The plg2 gene is
      characterized by an open reading frame of 1400 nucleotides and codes for a
      polypeptide of 383 amino acids. The plg1 gene 5'-flanking region contains
      putative binding sites for the transcription factors involved in regulation by
      ambient pH and catabolite repression. The primary structure of Plg1 and Plg2
      proteins showed a relatively high homology (varying between 32.4% and 74.8%) to
      fungal pectin lyases characterized to date. Southern blotting analysis revealed
      that both genes are present as single copies in the fungus genome. Expression
      studies revealed a differing pattern of gene expression of plg1 and plg2 when
      mycelium was cultivated on medium containing different pectic components. Citric
      pectin followed by apple pectin were the carbon sources that best induced plg1
      expression, and transcripts were detected from 24 to 76 h. The expression of the
      plg2 gene was monitored by reverse transcriptase - polymerase chain reaction,
      since Northern analysis failed to detect hybridization signals. The differential
      expression of these genes may provide means for the fungus to adapt to various
      growth conditions.

PMID- 17215899
TI  - Targeted engineering of Azospirillum brasilense SM with indole acetamide pathway
      for indoleacetic acid over-expression.
AB  - Rhizospheric bacterial strains are known to produce indole-3-acetic acid (IAA)
      through different pathways, and such IAA may be beneficial to plants at low
      concentrations. IAA biosynthesis by a natural isolate of Azospirillum brasilense
      SM was studied and observed to be tryptophan-inducible and -dependent in nature.
      While our work demonstrated the operation of the indole pyruvic acid pathway, the
      biochemical and molecular evidence for the genes of the indole acetamide (IAM)
      pathway were lacking in A. brasilense SM. This led us to use the IAM pathway
      genes as targets for metabolic engineering, with the aim of providing an
      additional pathway of IAA biosynthesis and improving IAA levels in A. brasilense
      SM. The introduction of the heterologous IAM pathway, consisting of the iaaM and
      iaaH genes, not only increased the IAA levels by threefold but also allowed
      constitutive expression of the same genes along with efficient utilization of IAM
      as a substrate. Such an engineered strain showed a superior effect on the lateral
      branching of sorghum roots as well as the dry weight of the plants when compared
      with the wild-type strain. Such an improved bioinoculant could be demonstrated to
      enhance root proliferation and biomass productivity of treated plants compared
      with the parental strain.

PMID- 17215900
TI  - Microbial communities in the larval midgut of laboratory and field populations of
      cotton bollworm (Helicoverpa armigera).
AB  - We compared the bacterial communities in the larval midgut of field and
      laboratory populations of a polyphagous pest, the cotton bollworm (Helicoverpa
      armigera), using denaturing gradient gel electrophoresis (DGGE) of amplified 16S
      rDNA sequences and 16S library sequence analysis. DGGE profiles and 16S rDNA
      library sequence analysis indicated similar patterns of midgut microbial
      community structure and diversity: specific bacterial types existed in both
      populations, and a more diverse microbial community was observed in caterpillars
      obtained from the field. The laboratory population harbored a rather simple gut
      microflora consisting mostly of phylotypes belonging to Enterococcus (84%). For
      the field population, phylotypes belonging to Enterococcus (28%) and Lactococcus
      (11%), as well as Flavobacterium (10%), Acinetobacter (19%), and Stenotrophomonas
      (10%) were dominant members. These results provided the first comprehensive
      description of the microbial diversity of the midgut of the important pest cotton
      bollworm and suggested that the environment and food supply might influence the
      diversity of the gut bacterial community.

PMID- 17215902
TI  - Expression regulation of the endochitinase-encoding gene sechi44 from the
      mycoparasite Stachybotrys elegans.
AB  - The regulation of the gene encoding the extracellular chitinase sechi44 produced
      by the mycoparasite Stachybotrys elegans was studied using real-time quantitative
      reverse-transcription polymerase chain reaction. Alteration of sechi44 expression
      was observed when S. elegans was in interaction with its host, Rhizoctonia
      solani, and also when the mycoparasite was grown on minimal media amended with
      different carbon and nitrogen sources. Direct contact with R. solani leading to
      mycoparasitism significantly up-regulated the expression of sechi44, although the
      analysis showed that sechi44 was constitutively expressed but at substantially
      lower levels. In addition, the study of sechi44 over 12 days showed that its
      expression followed a cyclical pattern with peaks every 2 days, which suggests
      that this gene has a role not only in mycoparasitism but also in growth. The
      addition of external carbon sources, such as N-acetylglucosamine, chitin, and R.
      solani cell wall (simulated mycoparasitism), triggered an increase in the
      expression of sechi44, which varied with time and carbon source. Among the carbon
      sources examined, N-acetylglucosamine induced the highest increase in sechi44
      transcript levels. The addition of high concentrations of glucose and ammonium
      triggered a decrease of sechi44 expression, suggesting that sechi44 is subject to
      glucose and ammonium repression.

PMID- 17215901
TI  - Intranasal immunization with a recombinant truncated FimH adhesin adjuvanted with
      CpG oligodeoxynucleotides protects mice against uropathogenic Escherichia coli
      challenge.
AB  - In this work, we assessed the efficacy of an experimental intranasal vaccine
      against urinary-tract infections. The vaccine contained a recombinant truncated
      FimH (rFimHt) adhesin plus CpG oligodeoxynucleotides. The efficacy of the vaccine
      was compared with that of an intramuscular vaccine that was formulated with the
      same immunogen plus Freund's adjuvant. Our results show that serum immunoglobulin
      G titers of vaccinated animals were similarly enhanced in both cases. However,
      the intranasal vaccine elicited higher vaginal-wash-specific immunoglobulin A
      titers against rFimHt than the intramuscular route. Both vaccines reduced the in
      vivo colonization of the bladder by uropathogenic Escherichia coli more than 100
      fold in a murine cystitis model. Our results indicate that a recombinant
      truncated FimH adhesin plus CpG oligodeoxynucleotides is a suitable immunogenic
      combination that can contribute to the development of a highly efficacious
      urinary tract infection vaccine.

PMID- 17215903
TI  - Plasmid content and bacteriocin production by five strains of Lactococcus lactis
      isolated from semi-hard homemade cheese.
AB  - In this study, the plasmid content and bacteriocin production of natural isolates
      of lactococci were investigated. Five bacteriocin producing lactococcal strains
      (Lactococcus lactis subsp. lactis BGMN1-2, BGMN1-3, BGMN1-5, BGMN1-6, and BGMN2
      7) were isolated as nonstarter microflora of semi-hard homemade cheese and
      characterized. All isolates contained a number of plasmids. It was shown that
      lcnB structural genes for bacteriocin lactococcin B were located on large
      plasmids in all isolates. In the strains BGMN1-3 and BGMN1-5 proteinase prtP
      genes collocated with lcnB. Furthermore, these strains produced two additional
      bacteriocins (LsbA and LsbB) with genes responsible for their production and
      immunity located on the small rolling circle-replicating plasmid pMN5. Using
      deletion experiments of pMN5, minimal replicon of the plasmid and involvement of
      a bacteriocin locus in plasmid maintenance were identified. In addition, plasmid
      curing experiments showed that genes for catabolism or transport of 10
      carbohydrates in the strain BGMN1-5 were plasmid located.

PMID- 17215904
TI  - Enhanced solubilization of rock phosphate by Penicillium bilaiae in pH-buffered
      solution culture.
AB  - Little is known about how pH-buffering capacity affects phosphorus (P)
      solubilization by Penicillium bilaiae. This study compared solubilization of rock
      phosphate (RP) by P. bilaiae in nonbuffered (pH 5.0) and buffered (pH 7.0) media.
      Fungal growth reached the stationary phase around day 12 and was slightly
      enhanced in the buffered medium. The fungus reduced solution pH from 5.0 to 4.1
      in the nonbuffered medium and from 7.0 to 4.9 in the buffered medium by day 12.
      Phosphorus concentrations increased after day 9 more in the buffered than in the
      nonbuffered media (53 and 5 mg P x L(-1), respectively, on day 12). On day 12,
      higher concentrations of citric and oxalic acids were detected in the buffered
      (2.0 and 1.2 g x L(-1), respectively) than nonbuffered media (0.5 and 0.04 g x L(
      1), respectively). Solubilization of RP was simulated without P. bilaiae in
      solutions equivalent to the nonbuffered and buffered cultures of P. bilaiae grown
      with RP. After a 24 h incubation, the P concentrations were of similar magnitudes
      to those observed in the P. bilaiae culture (18 and 47 mg P x L(-1),
      respectively, in the nonbuffered and buffered media). Under increased pH
      buffering conditions, the enhanced production of citric and oxalic acids led to
      significant RP solubilization.

PMID- 17215905
TI  - Diurnal variability in concentrations and sources of Escherichia coli in three
      streams.
AB  - Microbial contamination is a major concern for drinking water worldwide. Many
      monitoring protocols that use one or very few samples are inadequate and
      introduce a very large margin of error. An intensive sampling program needs to be
      conducted to characterize the Escherichia coli concentrations of a source water
      stream prior to establishing a monitoring program so that the sample frequency
      can be determined statistically, based on an acceptable margin of error.
      Developing meaningful monitoring programs for managing bacterial water quality is
      dependant on scientific data that determine the bacterial sources. In this study,
      three streams from drinking water watersheds were sampled every 15 min over a 24
      h period on three different days to determine the concentrations of E. coli and
      to identify their sources, using ribosomal RNA finger printing (ribotyping). The
      concentrations of E. coli varied throughout the day in each of the three streams.
      Ribotyping identified many different animal sources of E. coli in the samples.
      The sources of E. coli varied significantly with stream (P < 0.001, df = 16). The
      development of monitoring programs for watersheds needs to consider the
      watershed, and care needs to be taken in selecting appropriate sample sites,
      sampling regime, and number of samples taken during each sampling period. This
      note provides a prescription for the development of monitoring programs for
      watersheds.

PMID- 17215906
TI  - Role of the Sulfolobus shibatae viral T6 initiator in conferring promoter
      strength and in influencing transcription start site selection.
AB  - Archaeal promoters contain a TATA-box, an adjacent upstream TFB-recognition
      element (BRE), and a downstream initiator (INR) region from which transcription
      originates. While the contribution of A-box and BRE to promoter strength is well
      established, the role of DNA sequences within the INR region and its vicinity on
      transcription efficiency and start site selection remains unclear. Here, I
      demonstrate using the strong Sulfolobus shibatae viral T6 promoter that either
      substitution of its natural sequence from -17 and beyond with plasmid DNA or
      introduction of point transversion mutations at +3, -2, -4, and -5 positions
      reduce promoter strength dramatically, whereas +1, -1, and -2 mutations influence
      the transcription start site. These data therefore reveal that the INR region
      plays a role as important as the BRE and the A-box in T6 gene transcription.

PMID- 17215920
TI  - Lensless imaging with partially coherent light.
AB  - Based on the fourth-order correlation of light, lensless imaging with incoherent
      or partially coherent light is investigated theoretically by use of classical
      optical coherence theory. A novel lensless optical system for implementing
      imaging is proposed. The visibility and quality of the image are influenced by
      the coherence and transverse size of the light source. The results suggest useful
      imaging applications in x-ray, gamma-ray, or other wavelengths where no effective
      lens is available, and they have potential applications in optical metrology and
      holography.

PMID- 17215921
TI  - Intracavity gain gratings.
AB  - Intracavity gain gratings are theoretically demonstrated to exhibit diffraction
      efficiencies that are 100 times larger than unity at pump powers substantially
      below the lasing threshold. Experiments performed using a Nd:YVO4 microlaser
      pumped below threshold by two interfering Ti:sapphire laser beams are described.
      Huge enhancement of the diffraction efficiency (5000X) and a large increase of
      the angular selectivity (10X) are demonstrated despite the angular reduction of
      the Fabry-Perot cavity finesse. Much better results are expected using gain
      gratings with larger areas or thinner cavities such as vertical cavity surface
      emitting lasers. Such large fan-out values could be very interesting for
      applications to optical signal processing.

PMID- 17215923
TI  - Electrically tunable Bragg gratings in single-mode polymer optical fiber.
AB  - We present what is to our knowledge the first demonstration of a tunable fiber
      Bragg grating device in polymer optical fiber that utilizes a thin-film resistive
      heater deposited on the surface of the fiber. The polymer fiber was coated via
      photochemical deposition of a Pd/Cu metallic layer with a procedure induced by
      vacuum-ultraviolet radiation at room temperature. The resulting device, when
      wavelength tuned via joule heating, underwent a wavelength shift of 2 nm for a
      moderate input power of 160 mW, a wavelength to input power coefficient of -13.4
      pm/mW, and a time constant of 1.7 s(-1).

PMID- 17215922
TI  - Plasmon resonances in gold-coated tilted fiber Bragg gratings.
AB  - The transmission spectrum of fiber Bragg gratings with gratings planes tilted at
      a small angle (2 degrees -10 degrees) relative to the fiber axis shows a large
      number of narrowband cladding mode resonances within a 100 nm wide spectrum. When
      a gold coating with a thickness between 10 and 30 nm is deposited on the fiber,
      the transmission spectrum shows anomalous features for values of the outside
      medium refractive index between 1.4211 and 1.4499. These features are shown to
      correspond to the excitation of surface plasmon resonances at the external
      surface of the gold film.

PMID- 17215924
TI  - 25 GHz bandwidth Brillouin slow light in optical fibers.
AB  - Broadband slow light is demonstrated by using stimulated Brillouin scattering in
      optical fibers based on a double Brillouin pump, the peaks of which are
      spectrally separated by twice the Brillouin frequency. The loss spectrum
      generated by one of the pump waves is fully compensated by the gain spectrum of
      the other one, which permits the enlargement of the bandwidth to 25 GHz and a
      variable time delay of up to 10.9 ps with 37 ps pulses.

PMID- 17215925
TI  - Time delay enhancement in stimulated-Brillouin-scattering-based slow-light
      systems.
AB  - We show a simple method of time delay enhancement in slow-light systems based on
      the effect of stimulated Brillouin scattering. The method is based on the
      reduction of the absolute Brillouin gain by a loss produced by an additional pump
      laser. With this method we achieved pulse delays of nearly 100 ns in a standard
      single-mode fiber. In the presented approach the delay or acceleration of optical
      signals is decoupled from their amplification or attenuation, which allows the
      adaptation of the pulse amplitudes to the given application.

PMID- 17215926
TI  - Simple phase-only optical decryption with misalignment-free input.
AB  - An improved optical decryption system based on kinogram encoding is proposed. The
      decrypted phase image is obtained by optically descrambling the encrypted image
      with the decrypting phase key. Only a single Fourier lens is needed to generate
      intensity patterns from the decrypted phase image. The design and simulation
      results have confirmed the proposed technique as a novel, simple, and robust
      decryption architecture.

PMID- 17215927
TI  - Evaluation of diffraction catastrophes by using Weniger transformation.
AB  - Weniger transformation is a powerful nonlinear sequence transformation that, when
      applied to the sequence of the partial sums of a divergent or a slowly convergent
      series, can convert it to a fast-converging sequence. Weniger transformation is
      not yet well known in optics. Diffraction catastrophes are fundamental tools for
      evaluating an optical field in proximity to caustics and singularities. The
      action of the Weniger transformation on the power series representation of
      diffraction catastrophes is numerically studied for two particular cases,
      corresponding to the Airy and the Pearcey functions. The obtained results clearly
      show that Weniger transformation could become a computational tool of great
      importance for summing several types of series expansions in optics.

PMID- 17215928
TI  - Passive three-dimensional imaging using polarimetric diversity.
AB  - The results of experiments in developing a method for extracting three
      dimensional information from a scene by means of a polarimetric passive imaging
      sensor are summarized. This sensor provides a full Stokes vector at each sensor
      pixel location from which degree and angle of linear polarization are computed.
      The angle of linear polarization provides the azimuth angle of the surface normal
      vector. The depression angle of this surface normal vector is obtained in terms
      of the emitting object's index of refraction from the solution of an equation
      derived from Fresnel equations, Snell's law, and percent of linear polarization.
      Results of the application of this approach to simulated infrared polarimetric
      data are provided.

PMID- 17215929
TI  - Method of reconstructing wavefront aberrations by use of Zernike polynomials in
      radial shearing interferometers.
AB  - A novel method of reconstructing wavefront aberrations by use of Zernike
      polynomials for radial shearing interferometers is discussed. This method uses
      matrix formalism to calculate the Zernike coefficients of a wavefront under test
      and shows the validity of reconstructing an arbitrary wavefront aberration from
      an interferogram taken by a radial shearing interferometer. We also propose a new
      interferometer setup to determine the shape and the direction (concave or convex)
      of wavefront aberration in a single measurement.

PMID- 17215930
TI  - Comparison of cross-talk effects between colloidal quantum dot and conventional
      waveguides.
AB  - We present cross-talk calculations for a subdiffraction nanophotonic waveguide
      that consists of a colloidal quantum dot (QD) array 10 nm in diameter and compare
      the results with conventional continuous dielectric waveguides, assuming the same
      10 nm size as well as a 200 nm cutoff diameter for guided mode. We find that the
      QD cascade has much lower cross talk than 10 nm dielectric waveguides at an
      identical separation >30 nm. Moreover, results for 200 nm dielectric waveguides
      at a 280 nm gap are comparable with those of QD structures spaced 110 nm apart.
      Hence the proposed QD device is potentially superior to conventional waveguides
      in achieving lower cross talk in the subdiffraction regime and provides a new
      route to achieving high-density photonic integrated circuits.

PMID- 17215931
TI  - Design and demonstration of a high-energy booster amplifier for a high-repetition
      rate petawatt class laser system.
AB  - We have successfully developed a high-energy, high-repetition rate Ti:sapphire
      laser system that delivers 33 J before compression at 0.1 Hz. The final booster
      amplifier is based on a 100 mm diameter Ti:sapphire crystal pumped with 72 J of
      energy in six beams delivered by three frequency-doubled high-repetition rate
      Nd:glass lasers. This system is, to the best of our knowledge, the first
      demonstrated petawatt class laser system running at a high repetition rate.

PMID- 17215932
TI  - High-power 83 W holmium-doped silica fiber laser operating with high beam
      quality.
AB  - A high-power 83 W cladding-pumped Tm3+-Ho3+-doped silica fiber laser is reported.
      Using bidirectional 793 nm diode pumping, a maximum slope efficiency of 42% was
      produced after a threshold launched pump power of 12 W was exceeded. The laser
      operated at wavelengths near 2105 nm with moderate beam quality, i.e., M2
      approximately 1.5. Further power scaling of the fiber laser was limited by
      thermal failure of the fiber ends.

PMID- 17215933
TI  - Fiber laser using a microsphere resonator as a feedback element.
AB  - We show that a glass microsphere resonator can be used as a wavelength-selective
      mirror in fiber lasers. Due to their high quality factor (Q approximately 10(8)),
      microsphere resonators possess a narrow reflection bandwidth. This feature
      enables construction of single-frequency fiber lasers even when the laser cavity
      is long. Nonlinear effects (such as stimulated Raman lasing) were also observed
      in our setup at relatively low pump powers.

PMID- 17215934
TI  - High-efficiency 1040 and 1078 nm laser emission of a Yb:Y2O3 ceramic laser with
      976 nm diode pumping.
AB  - We report a high-efficiency diode-end-pumped polycrystalline Yb:Y2O3 ceramic
      laser. Pumped by a 976 nm laser diode bar and with an absorbed pump power of 2.8
      W, cw output power of 1.74 W at 1078 nm, and 0.73 W at 1040 nm were obtained. The
      slope efficiency was measured to be 82.4% for the 1078 nm laser emission and
      57.1% for the 1040 nm laser emission.

PMID- 17215935
TI  - Single-frequency 1.25 W monolithic lasers at 1123 nm.
AB  - Experimental investigation ofd Nd:YAG monolithic nonplanar ring lasers operated
      at 1123 nm wavelength is presented. Stable single-frequency 1123 nm laser output
      has been obtained with successful suppression of the strong 1064 nm radiation.
      Single-frequency output power of 1.25 W is demonstrated with a pump power of 3.98
      W at 808 nm, which gives a slope efficiency of 39%. The laser frequency tuning
      range is over 3 GHz, and the average tuning rate with temperature is -2.6 GHz/
      degrees C. A strong iodine absorption line can be covered within the laser
      frequency tuning range.

PMID- 17215936
TI  - Wide dynamic range detection of bidirectional flow in Doppler optical coherence
      tomography using a two-dimensional Kasai estimator.
AB  - We demonstrate extended axial flow velocity detection range in a time-domain
      Doppler optical coherence tomography (DOCT) system using a modified Kasai
      velocity estimator with computations in both the axial and transverse directions.
      For a DOCT system with an 8 kHz rapid-scanning optical delay line, bidirectional
      flow experiments showed a maximum detectable speed of >56 cm/s using the axial
      Kasai estimator without the occurrence of aliasing, while the transverse Kasai
      estimator preserved the approximately 7 microm/s minimum detectable velocity to
      slow flow. By using a combination of transverse Kasai and axial Kasai estimators,
      the velocity detection dynamic range was over 100 dB. Through a fiber-optic
      endoscopic catheter, in vivoM-mode transesophageal imaging of the pulsatile blood
      flow in rat aorta was demonstrated, for what is for the first time to our
      knowledge, with measured peak systolic blood flow velocity of >1 m/s, while
      maintaining good sensitivity to detect aortic wall motion at <2 mm/s, using this
      2D Kasai technique.

PMID- 17215937
TI  - Miniature near-infrared dual-axes confocal microscope utilizing a two-dimensional
      microelectromechanical systems scanner.
AB  - The first, to our knowledge, miniature dual-axes confocal microscope has been
      developed, with an outer diameter of 10 mm, for subsurface imaging of biological
      tissues with 5-7 microm resolution. Depth-resolved en face images are obtained at
      30 frames per second, with a field of view of 800 x 100 microm, by employing a
      two-dimensional scanning microelectromechanical systems mirror. Reflectance and
      fluorescence images are obtained with a laser source at 785 nm, demonstrating the
      ability to perform real-time optical biopsy.

PMID- 17215938
TI  - 4Pi microscopy with linear fluorescence excitation.
AB  - Practical 4Pi microscopy has so far exclusively relied on multiphoton excitation
      of fluorescence, because the nonlinear suppression of contributions from higher
      order sidelobes was mandatory for unambiguous axial superresolution. We show that
      novel lenses of 74 degrees semiaperture angle enable biological 4Pi microscopy
      with regular one-photon fluorescence excitation, thus increasing the signal and
      reducing system complexity and cost. An axial resolution of 95 nm, corresponding
      to a more than fourfold improvement over confocal microscopy, is verified in the
      imaging of microtubules in mammalian cells.

PMID- 17215939
TI  - Noncollinear double quasi phase matching in one-dimensional poled crystals.
AB  - We demonstrate simultaneous phase matching of two different nonlinear processes,
      using a noncollinear interaction in periodically poled crystal with single
      grating. The noncollinear scheme provides phase-matching solutions over
      continuous regions of the optical spectrum and can be used for multiple-harmonic
      generation as well as all-optical effects. We have demonstrated experimentally
      third-harmonic generation of a 3 microm pump wavelength in a noncollinear
      configuration using a periodically poled LiNbO3 crystal. We observed, in good
      agreement with theoretical calculation, very broad spectral and thermal
      acceptance bandwidths, as well as a relatively narrow angular bandwidth.

PMID- 17215940
TI  - Enhancement and inhibition of second-harmonic generation and absorption in a
      negative index cavity.
AB  - We study second-harmonic generation in a negative-index material cavity. The
      transmission spectrum shows a bandgap between the electric and magnetic plasma
      frequencies. The nonlinear process is made efficient by local phase-matching
      conditions between a forward-propagating pump and a backward-propagating second
      harmonic signal. By simultaneously exciting the cavity with counterpropagating
      pulses, and by varying their relative phase difference, one is able to enhance or
      inhibit linear absorption and the second-harmonic conversion efficiency.

PMID- 17215941
TI  - Second-harmonic generation of light at 544 and 272 nm from an ytterbium-doped
      distributed-feedback fiber laser.
AB  - We report external cavity second-harmonic generation of light at 544 and 272 nm
      based on an ytterbium-doped distributed-feedback fiber laser. The nonlinear
      crystal used to generate light at 544 nm is LiNbO3, and the maximum output of the
      cavity is 845 mW, corresponding to a conversion efficiency of 55%. In a second
      frequency-doubling step, using a beta-BaBa2O4 crystal, we generate up to 115 mW
      of light at 272 nm with a conversion efficiency of 14%.

PMID- 17215942
TI  - Nonlinear shift of spatial solitons at a graded dielectric interface.
AB  - We investigate total internal reflection of optical spatial solitons at the
      interface between two regions of nematic liquid crystals with different optical
      densities. Due to nonlinear molecular reorientation, the solitons experience a
      penetration depth, hence, a lateral shift that depends on the excitation, with
      lateral shifts from 0.7 to 1.2 mm as input powers increased from 1.6 to 9.3 mW.

PMID- 17215943
TI  - Wavelength-agile mid-infrared (5-10 microm) generation using a galvano-controlled
      KTiOPO4 optical parametric oscillator.
AB  - A wavelength-agile mid-infrared (IR) ZnGeP2 (ZGP) optical parametric oscillator
      (OPO) using a galvano-controlled double-crystal KTiOPO4 (KTP) OPO was
      demonstrated. The mid-IR wavelength was tuned by varying the KTP OPO pump
      wavelength while the ZGP crystal angle remained fixed. Rapid tuning of the KTP
      OPO was achieved by changing the crystal angle by using the galvano scanner. Our
      mid-IR source can jump to a different wavelength without scanning through the
      intermediate wavelengths while also permitting continuous-wavelength scanning.
      The mid-IR source can be tuned from approximately 5to10 microm at a phase
      matching angle of 51 degrees , while the pump wavelength is controlled in the
      1.95-2.2 microm range.

PMID- 17215944
TI  - Rewritable polarization-encoded multilayer data storage in 2,5-dimethyl-4-(p
      nitrophenylazo)anisole doped polymer.
AB  - We report a rewritable polarization-encoded multilayer data storage method with a
      polymer film doped with the azo dye DMNPAA (2,5-dimethyl-4-(p
      nitrophenylazo)anisole). It is found that under two-photon excitation by a
      linearly polarized femtosecond laser beam at wavelength 780 nm the optical axis
      of DMNPAA molecules can be oriented to the perpendicular direction of the beam
      via a trans-cis-trans isomerization process. As a result, multilayer polarization
      encoded optical data storage is demonstrated by recording two letters of a bit
      spacing of 4 microm in the same region of a given layer. It is shown that erasing
      and rewriting a particular layer is possible.

PMID- 17215945
TI  - Eliminating the longitudinal piston error between tiled gratings by angle tuning.
AB  - In a tiled-grating system, it is difficult to make two tiled gratings strictly
      coplanar. We propose and demonstrate for the first time, as far as we know, a
      simple method by which the longitudinal piston error between two tiled gratings
      can be reduced below lambda/10, close to the influence of the environmental
      factors. The alignment precision of the method increases with the tiled-grating
      system's stability to environmental factors.

PMID- 17215946
TI  - Disorder-immune coupled resonator optical waveguide.
AB  - We demonstrate that a photonic lattice with short- and long-range harmonic
      modulations of the refractive index facilitates formation of flat photonic bands
      and leads to slow propagation of light. The system can be considered a coupled
      resonator optical waveguide (CROW): photonic bands with abnormally small
      dispersion are created due to the interaction of long-lived states in the cavity
      regions via weak coupling across tunneling barriers. Unlike previous CROW
      implementations, the proposed structures can be fabricated with interference
      photolithography (holography), sidestepping the issue of resonator-to-resonator
      fluctuation of the system parameters. The proposed holography-based approach
      enables fabrication of arrays with a large number of coupled optical resonators,
      which is necessary for practical applications.

PMID- 17215947
TI  - Ultrafast extreme ultraviolet holography: dynamic monitoring of surface
      deformation.
AB  - We demonstrate femtosecond time-resolved dynamic Gabor holography using highly
      coherent extreme ultraviolet light generated by high harmonic upconversion of a
      femtosecond laser. By reflecting this light from an impulsively heated surface,
      we implement a simple and robust single-reflection geometry for phase-sensitive
      holographic detection at extreme UV wavelengths. Using this setup, we study the
      ultrafast deformation and subsequent acoustic oscillations within a thin metal
      film. These measurements exhibit subpicometer spatial sensitivity in the vertical
      dimension.

PMID- 17215948
TI  - Effect of disorder on slow light velocity in optical slow-wave structures.
AB  - Slow-wave optical structures such as coupled photonic crystal cavities, coupled
      microresonators, and similar coupled-resonator optical waveguides are being
      proposed for slowing light because of the nature of their dispersion
      relationship. Since the group velocity becomes small, slow light and enhanced
      light-matter interaction may be observed at the edges of the waveguiding band. We
      derive a model of the effects of disorder on slow light in such structures,
      obtaining a relationship between the root-mean-square variation in the coupling
      coefficients and how slow the light is at the band edge.

PMID- 17215949
TI  - Virtual sources for a cosh-Gaussian beam.
AB  - On the basis of superposition of beams, a group of virtual sources that generate
      a cosh-Gaussian wave is identified. A closed-form expression is derived for this
      cosh-Gaussian wave, which, in the appropriate limit, yields the paraxial
      approximation for the cosh-Gaussian beam. From this expression, the paraxial
      approximation and the nonparaxial corrections of all orders for the corresponding
      paraxial cosh-Gaussian beam are determined.

PMID- 17215950
TI  - Large dielectrophoresis force and torque induced by localized surface plasmon
      resonance of Au nanoparticle array.
AB  - A new approach is proposed for manipulating and rotating micro- or nano-objects
      by using polarized laser light with low intensity. The polarized light excites
      resonant dipoles on a cap-shaped Au nanoparticle array, which generates a highly
      nonuniform radiation field that induces large dielectrophoresis force on
      dielectric objects. The orientation control of the objects is realized by
      adjusting the polarization direction of the incident light. Theoretical modeling,
      fabrication, and characterization results for the cap-shaped Au nanoparticle
      array, as well as preliminary trapping results, are reported.

PMID- 17215951
TI  - Nondiffracting random intensity patterns.
AB  - We report a simple approach for generating nondiffracting random intensity
      patterns that do not change with propagation. Experimental results are shown
      where the generating patterns are encoded onto a phase-only liquid-crystal
      display. We expect that these results will be useful for encryption or
      surveillance applications.

PMID- 17215952
TI  - Frequency-coded quantum key distribution.
AB  - We report an intrinsically stable quantum key distribution scheme based on
      genuine frequency-coded quantum states. The qubits are efficiently processed
      without fiber interferometers by fully exploiting the nonlinear interaction
      occurring in electro-optic phase modulators. The system requires only integrated
      off-the-shelf devices and could be used with a true single-photon source.
      Preliminary experiments have been performed with weak laser pulses and have
      demonstrated the feasibility of this new setup.

PMID- 17215953
TI  - Single quantum dots for slow and fast light in a planar photonic crystal.
AB  - We theoretically investigate slow and fast light propagation and pulse velocity
      control in a nanocavity containing a single quantum dot side-coupled to a planar
      photonic-crystal waveguide. We demonstrate that low coupling strength (i.e., the
      weak coupling regime) between a cavity and a dot, under on-resonance condition,
      can lead to delays of about +90 ps for a pulse 1/e-width of 280 ps. The group
      delay dependence on the various coupling parameters suggests achievable delays of
      +300 ps and consequently very slow light speeds of around 5000 m/s in a 1.5
      microm cavity-waveguide section. We also show that under off-resonant condition
      one can achieve significant pulse advancement of -60 ps.

PMID- 17215954
TI  - Cavity-ringdown molecular spectroscopy based on an optical frequency comb at 1.45
      1.65 microm.
AB  - Optical frequency comb-based cavity-ringdown spectroscopy has recently enabled
      high-sensitivity absorption detection of molecules over a broad spectral range.
      We demonstrate an improved system based on a mode-locked erbium-doped fiber laser
      source centered at 1.5 microm, resulting in a spectrometer that is inexpensive,
      simple, and robust. It provides a very large spectral bandwidth (1.45-1.65
      microm) for investigation of a wide variety of molecular absorptions. Strong
      molecular absorptions at 1.5 mum allow for detection at sensitivities approaching
      the 1 part in 10(9) volume level. We provide a detailed description of our
      spectrometer and present measurements of the rovibrational spectra for CO, NH3,
      and C2H2 with an absorption sensitivity of 2 x 10(-8) cm(-1)Hz(-1/2) per
      detection channel.

PMID- 17215955
TI  - Double plasma mirror for ultrahigh temporal contrast ultraintense laser pulses.
AB  - We present and characterize a very efficient optical device that employs the
      plasma mirror technique to increase the contrast of high-power laser systems.
      Contrast improvements higher than 10(4) with 50% transmission are shown to be
      routinely achieved on a typical 10 TW laser system when the pulse is reflected on
      two consecutive plasma mirrors. Used at the end of the laser system, this double
      plasma mirror preserves the spatial profile of the initial beam, is unaffected by
      shot-to-shot fluctuations, and is suitable for most high peak power laser
      systems. We use the generation of high-order harmonics as an effective test for
      the contrast improvement produced by the double plasma mirrors.

PMID- 17215956
TI  - Single-shot spatiotemporal measurements of high-field terahertz pulses.
AB  - The electric field profiles of broad-bandwidth coherent terahertz (THz) pulses,
      emitted by laser-wakefield-accelerated electron bunches, are studied. The near
      single-cycle THz pulses are measured with two single-shot techniques in the
      temporal and spatial domains. Spectra of 0-6 THz and peak fields up to
      approximately or = 0.4 MV cm(-1) are observed. The measured field substructure
      demonstrates the manifestation of spatiotemporal coupling at focus, which affects
      the interpretation of THz radiation as a bunch diagnostic and in high-field pump
      probe experiments.

PMID- 17215957
TI  - Nerve growth factor mRNA expression in the regenerating antler tip of red deer
      (Cervus elaphus).
AB  - Deer antlers are the only mammalian organs that can fully regenerate each year.
      During their growth phase, antlers of red deer extend at a rate of approximately
      10 mm/day, a growth rate matched by the antler nerves. It was demonstrated in a
      previous study that extracts from deer velvet antler can promote neurite
      outgrowth from neural explants, suggesting a possible role for Nerve Growth
      Factor (NGF) in antler innervation. Here we showed using the techniques of
      Northern blot analysis, denervation, immunohistochemistry and in situ
      hybridization that NGF mRNA was expressed in the regenerating antler, principally
      in the smooth muscle of the arteries and arterioles of the growing antler tip.
      Regenerating axons followed the route of the major blood vessels, located at the
      interface between the dermis and the reserve mesenchyme of the antler.
      Denervation experiments suggested a causal relationship exists between NGF mRNA
      expression in arterial smooth muscle and sensory axons in the antler tip. We
      hypothesize that NGF expressed in the smooth muscle of the arteries and
      arterioles promotes and maintains antler angiogenesis and this role positions NGF
      ahead of axons during antler growth. As a result, NGF can serve a second role,
      attracting sensory axons into the antler, and thus it can provide a guidance cue
      to define the nerve track. This would explain the phenomenon whereby re
      innervation of the regenerating antler follows vascular ingrowth. The annual
      growth of deer antler presents a unique opportunity to better understand the
      factors involved in rapid nerve regeneration.

PMID- 17215958
TI  - A highly pathogenic strain of Staphylococcus sciuri caused fatal exudative
      epidermitis in piglets.
AB  - Staphylococcus sciuri are important human pathogens responsible for endocarditis,
      peritonitis, septic shock, urinary tract infection, pelvic inflammatory disease
      and wound infections. However, little information is known regarding the
      pathogenicity of S. sciuri to animals. From the pericardial fluid of a diseased
      piglet with exudative epidermitis (EE), we isolated a strain of Staphylococcus in
      pure culture. Surprisingly, this isolate was a member of S. sciuri rather than S.
      hyicus as identified by its biochemical traits and also by analysis of 23S
      ribosomal DNA using Internal Transcribed Spacer PCR. In addition, inoculation of
      newborn piglets with 1x10(10) CFU of the isolate by oral feeding or intra
      muscular injection successfully reproduced EE in piglets, which suggested that
      the oral intake of the pathogen by the animals is one of the major routes of
      exposure. These unexpected findings prioritized S. sciuri as important zoonotic
      agents, which may have ramifications for human medicine.

PMID- 17215960
TI  - Preventing Alcohol Abuse among Early Adolescents through Family and Computer
      Based Interventions: Four-Year Outcomes and Mediating Variables.
AB  - III-timed and excessive use of alcohol is associated with multiple and
      irreversible disabilities. The relationship between perinatal alcohol use and
      developmental disabilities, including fetal alcohol syndrome, is well documented.
      Empirical evidence also links alcohol use to a host of other developmental and
      physical problems among the offspring of drinkers and among drinkers themselves.
      Toward advancing the science of how to reduce alcohol abuse risks, this study
      developed and tested family and computer-based approaches for preventing alcohol
      use among a community sample of inner-city minority youth. Original findings from
      4-year follow-up data obtained from over 90% of the study sample document
      continued positive program outcomes and shed light on cognitive problem solving,
      peer, and family mediators of alcohol use risk and protective factors among
      target youth.

PMID- 17215959
TI  - Signaling from p53 to NF-kappa B determines the chemotherapy responsiveness of
      neuroblastoma.
AB  - Neuroblastic (N) type neuroblastoma (NB) is the predominant cell type in NB
      tumors. Previously, we determined that activated nuclear factor kappaB (NF
      kappaB) is required for doxorubicin and etoposide to kill N-type NB cells. This
      study was undertaken to determine how NF-kappaB is activated by these agents. The
      results show that p53 protein levels increase within 15 to 30 minutes of
      treatment. This increase occurs before the degradation of inhibitor of NF-kappaB
      (I-KB) alpha and the NF-kappaB-dependent activation of gene transcription.
      Moreover, p53 is necessary for NF-kappaB activation because cells with inactive
      p53 were resistant to NF-kappaB-mediated cell death. This pathway was further
      defined to show that p53 leads to the activation of MAPK/ERK activity kinase
      (MEK) 1 through a process that depends on protein synthesis and H-Ras. MEK1, in
      turn, mediates I-kappaB kinase activation. Together, these results demonstrate
      for the first time how NF-kappaB is activated in NB cells in response to
      conventional drugs. Furthermore, these findings provide an explanation as to why
      H-Ras expression correlates with a favorable prognosis in NB and identify
      intermediary signaling molecules that are targets for discovering treatments for
      NB that is resistant to conventional agents.

PMID- 17215962
TI  - Nikolai N. Anichkov and his theory of atherosclerosis.
AB  - Nikolai N. Anichkov (1885-1964) first demonstrated the role of cholesterol in the
      development of atherosclerosis. His classic experiments in 1913 paved the way to
      our current understanding of the role of cholesterol in cardiovascular disease.
      Anichkov's research is often cited among the greatest discoveries of the 20th
      century; however, little is known about Anichkov and his team. Herein, we give a
      detailed historical account of Anichkov's work, his personality, his research
      team, and their pioneering effort.

PMID- 17215964
TI  - A new protocol for quantifying CD34(+) cells in peripheral blood of patients with
      cardiovascular disease.
AB  - Increasing evidence points to a role for circulating CD34-positive (CD34(+))
      cells in vascular maintenance and neovascularization. Although there are
      established methods for evaluating absolute numbers of CD34(+) cells in bone
      marrow or mobilized peripheral blood, there is no convenient and highly
      reproducible method for quantifying low numbers of CD34(+) cells in blood
      samples, such as those from the peripheral blood of patients with cardiovascular
      disease. With current commonly used methods, the mean percentage of CD34(+) cells
      in leukocyte fractions from such patients was only 0.02%, and the cumulative
      intra-assay coefficient of variation was approximately 30%. With use of the
      protocol described herein, actual counts of CD34(+) cells increased approximately
      5-fold and cumulative intra-assay coefficients of variation were reduced to
      approximately 7%. The new method is useful to precisely measure low numbers of
      CD34(+) cells in samples, and it has potential as a screening tool to evaluate
      cardiovascular risk in large patient populations.

PMID- 17215963
TI  - A proposed alternative mechanism of action for transmyocardial revascularization
      prefaced by a review of the accepted explanations.
AB  - Laser transmyocardial revascularization, a procedure originally intended to
      simulate the perfusion mechanism of the reptilian heart, has evolved into an
      effective but poorly understood treatment for angina when traditional
      revascularization is not an option. Herein, we review the explanations that have
      been proposed over the years and suggest a new one. We hypothesize that the long
      term mechanism of action of transmyocardial revascularization is the
      redistribution of stresses on the ventricular wall through the creation of
      fibrous transmyocardial scars, which penetrate the various layers of muscle that
      surround the left ventricular cavity. The stress redistribution of a load in an
      otherwise unchanged ventricular wall reduces the wall stress per unit of wall
      volume, which in turn decreases the workload for the hyperkinetic compensating
      areas. This reduces both oxygen demand and local metabolite production, lowering
      the level of angina.

PMID- 17215965
TI  - Flow analysis of left internal thoracic artery in myocardial revascularization
      surgery using y graft.
AB  - In order to evaluate the left internal thoracic artery flow pattern, when the
      vessel is used as a graft to supply the left coronary artery system, we evaluated
      flow by Doppler measurement, both at rest and under dobutamine stress. There were
      2 groups of 20 patients each: group A patients received only a left internal
      thoracic artery graft to the left anterior descending artery, and group B
      patients received a pedicled left internal thoracic artery graft associated with
      a vein graft, which together supplied the left anterior descending artery and
      another branch of the left coronary artery. Angiography showed patent grafts in
      all patients from both groups. The following characteristics were evaluated:
      systolic flow, diastolic flow, total flow, total flow under stress/total flow at
      rest ratio, systolic peak velocity, diastolic peak velocity, and systolic peak
      velocity/diastolic peak velocity ratio. In group A, the total flow was 45.5 +/-
      21.6 mL/min at rest and 68.3 +/- 32.9 mL/min under stress. In group B, the total
      flow was 98.2 +/- 50.4 mL/min at rest and 175.7 +/- 79.2 mL/min under stress.
      Comparison between groups showed a total flow increase in group B of 115.8%
      (P=0.0002) at rest and 157.2% (P <0.0001) under stress. The other characteristics
      were also statistically significant, except systolic flow, total flow under
      stress/total flow at rest ratio, and systolic peak velocity. Our results showed
      that the left internal thoracic artery sufficiently supplies regional myocardium
      at rest and during exercise (stress), demonstrating its great adaptability in
      response to demand.

PMID- 17215966
TI  - Hyperexpansion of coronary stents and clinical outcomes.
AB  - The complication rates and late clinical follow-up of patients who experience
      stent hyperexpansion have not been well studied. We designed this prospective
      study to evaluate the influence of stent hyperexpansion on clinical outcomes in
      patients with coronary artery disease. Patients who underwent coronary stenting
      were divided into 2 groups according to whether or not their stents hyperexpanded
      (defined as stent/artery luminal diameter ratio of > or =1.1/1.0 with no residual
      stenosis) during implantation. Clinical, angiographic, and procedural
      characteristics were evaluated at baseline, and clinical outcomes were analyzed
      in-hospital and at 1 year. The primary endpoint comprised 1-year major adverse
      cardiovascular events (MACE): death, myocardial infarction, and target-vessel
      revascularization. Clinical characteristics were not statistically different
      between patients with hyperexpansion (n=94) and those without (n=542; controls).
      The hyperexpansion group had significantly smaller mean target-vessel diameters
      and less severe stenoses; their stents were implanted at higher pressures (13.51
      +/- 12.93; P=0.01); and they had higher balloon/artery ratios (1.07 U vs 0.99 U;
      P <0.0001) and higher aggressiveness scores (14.5 U vs 12.79 U; P <0.0001). Rates
      of angiographic success and in-hospital MACE were similar, although the
      hyperexpansion group more often had occlusions of large side branches (5.3% vs
      1.5%; P=0.03). At 1 year, the groups had similar rates of MACE (10.8% vs 10.7%),
      including target-vessel revascularization (8.2% vs 6.5%). Multivariate analysis
      revealed associations between stent hyperexpansion and higher aggressiveness
      scores, higher balloon/artery ratios, and narrower target vessels; the
      hyperexpansion group also had more target-vessel large-side-branch occlusions.
      Hyperexpansion was not associated with lower rates of MACE.

PMID- 17215967
TI  - Continuous insulin infusion improves postoperative glucose control in patients
      with diabetes mellitus undergoing coronary artery bypass surgery.
AB  - Postoperative glucose control directly affects the incidence of deep sternal
      wound infection and death after patients with diabetes have undergone coronary
      artery bypass grafting. We compared the effect upon glucose control of continuous
      insulin infusion with that of glucometer-guided insulin injection after coronary
      artery bypass. Our prospective, randomized, controlled study involved patients
      with diabetes mellitus who underwent coronary artery bypass grafting in our
      hospital from January 2001 through January 2003. Immediately after surgery,
      patients were randomly assigned to receive continuous insulin infusion or
      conventional glucometer-guided injection to maintain blood glucose at a level
      between 150 and 200 mg/dL. The adequacy of postoperative blood glucose control
      and clinical outcome were evaluated. Of 93 patients studied, the incidence of
      sternal wound infection was 3.9% among infusion patients and 4.8% among injection
      patients (P=0.587). There was no significant difference in mortality rates
      (infusion, 3.9%; injection, 2.4%; P=0.573). Satisfactory blood glucose levels
      were achieved in significantly more patients undergoing infusion than injection
      (64.7% vs 28.6%, P <0.001). In the injection group, significantly more blood
      glucose measurements were required to achieve control (23.4 vs 16.5, P=0.001),
      and good control was attained much sooner in the infusion group (21.4 vs 30.5 hr,
      P=0.013). We conclude that continuous insulin infusion provides better control of
      postoperative blood glucose levels after coronary artery bypass grafting in
      patients with diabetes than does glucometer-guided insulin injection.

PMID- 17215968
TI  - Directed retrograde cerebral protection during moderate hypothermic circulatory
      arrest.
AB  - There are many choices for neurologic protection for aortic arch surgery.
      Although numerous investigators have challenged the efficacy of retrograde
      cerebral perfusion, we have had good results with our application of this
      technique. We performed a retrospective review of 8 consecutive patients who
      underwent surgery from 1 June 2001 through 31 March 2003; the age range was 33 to
      97 years. All patients required circulatory arrest and underwent retrograde
      cerebral perfusion with use of a tourniquet on the patients' left and right arms
      above the elbow to direct retrograde flow to the brain. Moderate hypothermia
      (around 24 degrees C nasopharyngeal) was used; circulatory arrest time ranged
      from 27 to 63 minutes. There was 1 late hospital death due to multiple-organ
      system failure. There were no neurologic complications (stroke or temporary
      neurologic dysfunction). There was no substantive neurologic or renal dysfunction
      in this cohort, in which moderate hypothermia was used. These results are
      comparable to those reported in the literature for similar patients. We conclude
      that, for patients who require circulatory arrest, directed retrograde cerebral
      perfusion at moderate nasopharyngeal hypothermia gives results comparable to
      those reported with other techniques.

PMID- 17215969
TI  - Predictors of permanent pacemaker implantation during the early postoperative
      period after valve surgery.
AB  - The ability to preoperatively identify patients who may require permanent
      pacemaker implantation is rather poorly understood. The aim of this study is to
      determine the current incidence of permanent pacing after valve surgery and to
      determine which factors place the heart valve patient at risk of requiring
      permanent pacemaker implantation. We audited the records of 2,392 consecutive
      adult patients who underwent cardiac valve surgical procedures by the same
      surgical team from 25 April 1998 through 31 March 2003. Of these, 118 patients
      (group A) required the postoperative implantation of permanent pacemakers during
      the same hospitalization; they were compared with 1,959 heart valve patients
      (group B) who did not require pacemaker placement. Multivariate logistic
      regression analysis showed that reoperations (odds ratio [OR], 8.23; P <0.001),
      longer cumulative cross-clamp times (OR, 5.9; P <0.001), multiple-valve surgical
      procedures (OR, 3.46; P <0.05), and absence of preoperative sinus rhythm (OR
      2.52; P <0.001) were independent predictors of the need for permanent pacemaker
      implantation after valve surgery. These results suggest that patients who display
      these risk factors for arrhythmias that require permanent pacemaker implantation
      receive closer observation and advance counseling about the likelihood of such
      implantation.

PMID- 17215970
TI  - Hybrid coronary revascularization in high-risk patients.
AB  - From January 2002 through June 2004, 17 patients (2% of all coronary cases) were
      treated with off-pump coronary artery bypass grafting combined with percutaneous
      coronary intervention. There were 13 men and 4 women, whose ages ranged from 54
      to 78 years (mean, 63.1 +/- 20.9 yr). Preoperative angiography revealed 2-vessel
      coronary artery disease in 12 patients and 3-vessel disease in the remaining 5
      patients. In all patients, extensive lesions (>50%) in the circumflex and right
      coronary arteries were treated first with a percutaneous intervention, followed
      by beating-heart coronary artery bypass grafting within 3 hours to treat the
      remaining obstructed vessels. Coronary angiography was performed 12 months after
      the operation to evaluate the effectiveness of the procedure. Procedure-related
      complications did not occur, and there was no in-hospital death. All patients
      underwent a successful left internal mammary artery-left anterior descending
      artery anastomosis with the exception of 1 patient, in whom we used a saphenous
      vein because of previous chest radiotherapy. The postoperative courses were
      uneventful, and no deterioration of preoperative organ dysfunction was noticed in
      any patient. There was no cardiac-related death or myocardial infarction. In
      follow-up angiography, all left internal mammary artery-left anterior descending
      artery anastomoses were patent. Three patients with restenosis were treated
      medically, which resulted in substantial reduction of angina. Hybrid coronary
      revascularization enables complete revascularization and may be an alternative
      method of treating selected patients who have concomitant disease.

PMID- 17215971
TI  - The diameters of the aorta and its major branches in patients with isolated
      coronary artery ectasia.
AB  - We designed this study to evaluate the diameters of the aorta and its major
      branches in patients who had coronary ectasia. We assigned 80 patients (mean age,
      57 +/- 11 yr) with isolated coronary artery ectasia to the study group and 25
      patients (mean age, 54 +/- 10 yr) without structural or coronary arterial disease
      to the control group. All patients underwent coronary angiography and angiography
      of the aorta and its branches. We used computed quantitative angiography to
      measure the diameters of the coronary arteries, the aorta, and the major aortic
      branches. Within the study group, the diameter indices of the proximal portions
      of the right common iliac artery (P=0.041) and the left common iliac artery
      (P=0.035) were significantly larger than the diameter indices within the control
      group. The diameter indices of all other evaluated arteries were similar in both
      groups (all P >0.05).

PMID- 17215972
TI  - Tandem pedicled internal thoracic artery conduit for sequential grafting of
      multiple left anterior descending coronary artery lesions.
AB  - A patient presented with severe triple-vessel coronary artery disease, including
      multiple lesions on the left anterior descending coronary artery (LAD), which
      supplied a well-contracting myocardium. In approaching our patient, we judged
      that a pedicled left internal thoracic artery (LITA) would not provide enough
      length for sequential grafting of the multisegment-diseased LAD. We also
      considered that a pedicled right internal thoracic artery (RITA) conduit would
      not be long enough to provide a free segment that would form a tandem graft with
      a LITA and then arrive at the marginal branch, unless it was detached at its
      origin. Consequently, we decided to form a composite graft that would connect a
      free, short segment (6-7 cm) of pedicled LITA to the in situ pedicled RITA, in an
      end-to-end fashion. This new composite conduit enabled us to perform sequential
      grafting (3 sequential anastomoses, 2 with the LITA segment) of the multisegment
      diseased LAD, following the route anterior to the aorta. The in situ remnant of
      the LITA was grafted to the marginal branch. Although many large series have
      reported resourceful solutions, to the best of our knowledge, tandem arterial
      sequential grafting (an in situ pedicled RITA plus a free, short segment of a
      pedicled LITA) has not heretofore been reported in application to the
      multisegmented-diseased LAD artery. We strongly believe that this technique is an
      attractive variation on bilateral pedicled ITA left-sided revascularization in
      cases of multivessel coronary artery disease, including LADs with multiple
      lesions.

PMID- 17215973
TI  - Retrograde pulmonary perfusion improves results in pulmonary embolectomy for
      massive pulmonary embolism.
AB  - Mortality rates for pulmonary embolectomy in patients with acute massive
      pulmonary embolism have decreased in recent years. However, they still range from
      30% to 45% when the surgery is performed on critically ill patients, and the
      rates reach 60% in patients who have experienced cardiac arrest before the
      procedure. The causes of death in these patients are generally attributed to
      right heart failure due to persistent pulmonary hypertension, intractable
      pulmonary edema, and massive parenchymal and intrabronchial hemorrhage. Clinical
      and experimental findings indicate that venous air embolism causes severe or even
      lethal damage to the pulmonary microvasculature and the lung parenchyma
      consequent to the release of endothelium-derived cytokines. These findings are
      similar to those observed when severely compromised patients undergo pulmonary
      embolectomy-air entrapped in the pulmonary artery during embolectomy can lead to
      fatal outcomes. Besides enabling the removal of residual thrombotic material from
      the peripheral branches of the pulmonary artery, retrograde pulmonary perfusion
      fills the pulmonary artery with blood and prevents pulmonary air embolism. In
      this retrospective study, we analyzed a series of 21 consecutive critically ill
      patients in whom we applied retrograde pulmonary perfusion while performing
      standard pulmonary embolectomy. No patient died or experienced major
      postoperative complications. We believe that the use of retrograde pulmonary
      perfusion decreases morbidity and mortality rates associated with pulmonary
      embolectomy in critically ill patients.

PMID- 17215974
TI  - Surgical approaches to the aberrant right subclavian artery.
AB  - Aberrant subclavian artery (arteria lusoria) is a rare congenital anomaly that
      usually does not produce symptoms. Symptomatic patients require surgical
      intervention. The operative approach to correct this condition has been
      controversial. Herein, we describe surgical approaches to the aberrant right
      subclavian artery. From 2000 through 2004, 3 children and 1 adult with aberrant
      right subclavian artery underwent operation. Our surgical approach varied
      according to the age of the patient. A muscle-sparing right thoracotomy was used
      in the pediatric patients, and a supraclavicular approach was used in the adult.
      Patients were treated successfully by division of the aberrant right subclavian
      artery and translocation to the right common carotid artery, without graft
      interposition. There was no operative or late morbidity or death. Symptoms were
      completely relieved in all patients. Although an extrathoracic approach is
      applicable and reliable for adult patients, we believe that adequate exposure for
      the described procedure is best accomplished through a right thoracotomy in
      pediatric patients. This approach enables optimal mobilization of the distal
      right subclavian artery without leaving a long stump and enables direct
      anastomosis to the ipsilateral carotid artery.

PMID- 17215975
TI  - Arteriopathy in the high-performance athlete.
AB  - Pain occurs frequently in high-performance athletes and is most often due to
      musculoskeletal injury or strain. However, athletes who participate in sports
      that require highly frequent, repetitive limb motion can also experience pain
      from an underlying arteriopathy, which causes exercise-induced ischemia. We
      reviewed the clinical records and follow-up care of 3 high-performance athletes
      (mean age, 29.3 yr; range, 16-47 yr) who were admitted consecutively to our
      institution from January 2002 through May 2003, each with a diagnosis of limb
      ischemia due to arteriopathy. The study group comprised 3 males: 2 active in
      competitive baseball (ages, 16 and 19 yr) and a cyclist (age, 47 yr). Provocative
      testing and radiologic evaluation established the diagnoses. Treatment goals
      included targeted resection of compressive structures, arterial reconstruction to
      eliminate stenosis and possible emboli, and improvement of distal perfusion. Our
      successful reconstructive techniques included thoracic outlet decompression and
      interpositional bypass of the subclavian artery in the 16-year-old patient,
      pectoralis muscle and tendon decompression to relieve compression of the axillary
      artery in the 19-year-old, and patch angioplasty for endofibrosis affecting the
      external iliac artery in the 47-year-old. Each patient was asymptomatic on follow
      up and had resumed participation in competitive athletics. The recognition and
      anatomic definition of an arteriopathy that produces exercise-induced ischemia
      enables the application of precise therapy that can produce a symptom-free
      outcome and the ability to resume competitive athletics.

PMID- 17215976
TI  - Use of a percutaneous ventricular assist device for treatment of cardiogenic
      shock due to critical aortic stenosis.
AB  - We present the case of a 72-year-old woman who was transferred to our institution
      in cardiogenic shock and with multiple-organ failure, due to critical aortic
      stenosis. She was considered too high-risk to undergo aortic valve replacement. A
      TandemHeart percutaneous ventricular assist device was used to stabilize the
      patient's condition before surgery, and she subsequently underwent successful
      aortic valve replacement. To our knowledge, this is the 1st report in the
      literature of this particular application of the TandemHeart device.

PMID- 17215977
TI  - First use of the TandemHeart percutaneous left ventricular assist device as a
      short-term bridge to cardiac transplantation.
AB  - Advanced heart failure may be refractory despite aggressive support with
      inotropic agents and intra-aortic balloon pumping. Implantable left ventricular
      assist devices are increasingly being used as bridges to cardiac transplantation
      or as destination therapy because of the limited availability of donor organs. We
      report the 1st use of the TandemHeart percutaneous ventricular assist device as a
      short-term bridge to cardiac transplantation.

PMID- 17215978
TI  - Perforated submitral left ventricular aneurysm resulting in severe mitral annular
      regurgitation.
AB  - Annular submitral left ventricular aneurysm, which predominantly occurs in blacks
      who live in tropical regions of Africa, is a relatively unknown cardiac condition
      in the United States. We describe a patient with submitral left ventricular
      aneurysm who underwent resection of the mass and of the native mitral valve,
      followed by mitral valve replacement.

PMID- 17215979
TI  - Cardiac autotransplantation for surgical resection of a primary malignant left
      ventricular tumor.
AB  - Primary cardiac sarcomas are rare. In such tumors, surgical resection is
      sometimes considered necessary to correct obstruction of flow caused by the tumor
      and to accomplish complete resection. The anatomic difficulties associated with
      large, primary, intracavitary left-sided sarcomas have led us to use cardiac
      explantation, ex vivo tumor resection, and cardiac autotransplantation to meet
      the anatomic challenges of left atrial tumors. We report the case of a patient
      who had a large, primary, intracavitary, left ventricular sarcoma that was
      successfully removed by cardiac explantation and ex vivo reconstruction with use
      of the cardiac autotransplantation technique. This is the 1st report describing
      the use of cardiac autotransplantation to surgically resect an intracavitary left
      ventricular malignancy.

PMID- 17215980
TI  - Successful surgical treatment of massive pulmonary embolism after coronary bypass
      surgery.
AB  - Acute massive pulmonary embolism after cardiac surgery is very rare. Although
      accurate diagnosis and rapid treatment are crucial to a successful outcome, there
      is no standard treatment option. Thrombolytic therapy and catheter embolectomy
      are the usual treatment options, but they are associated with risks, especially
      in patients who experience massive pulmonary embolism after coronary artery
      bypass surgery. Open pulmonary embolectomy may be the best choice for treating
      these patients. This report describes our use of emergency pulmonary embolectomy
      along with cardiopulmonary bypass as an effective therapeutic approach in 2 cases
      of massive pulmonary embolism that occurred after on-pump coronary artery bypass
      grafting.

PMID- 17215981
TI  - Brugada syndrome unmasked by pneumonia.
AB  - A 69-year-old white woman presented at our emergency room with right-side
      pleuritic chest pain, fever, and tachycardia. Results of the physical
      examination, routine laboratory tests, and chest radiography were unexceptional.
      An electrocardiogram showed ST elevation in leads V(1) through V(3) with T-wave
      inversion. Because of the chest pain and the ST elevation, the patient underwent
      emergency cardiac catheterization, which showed no coronary artery stenosis. A
      computed tomographic scan of the chest showed pulmonary infiltration in the right
      middle lobe and the lingula of the left upper lobe; pneumonia was diagnosed, and
      appropriate antibiotic therapy was started. The electrocardiographic changes met
      the criteria for type-1 Brugada pattern. Brugada syndrome is an arrhythmogenic
      disease caused in part by mutations in the cardiac sodium channel gene SCN5A.
      When the sodium current is disrupted, the outward transient current at the end of
      phase 1 of the action potential becomes unopposed. This creates a voltage
      gradient between the epicardium and endocardium, especially in the right
      ventricular wall, which leads to J-point elevation in leads V(1) through V(3).
      Fever exaggerates this defect in sodium channels. In our patient, the pleuritic
      chest pain was caused by the pneumonia, and the ST elevation was probably related
      to Brugada syndrome, unmasked by the febrile episode. Brugada syndrome can be
      associated with ventricular tachycardia or fibrillation; the only treatment
      proven to prevent sudden death is placement of an implantable cardioverter
      defibrillator, which is recommended in symptomatic patients or in those with
      ventricular tachycardia induced during electrophysiologic studies.

PMID- 17215982
TI  - Left ventricular pseudoaneurysm after coronary artery bypass and valve
      replacement for post-infarction mitral regurgitation.
AB  - Most left ventricular inferior wall aneurysms are classified as false, and they
      have a narrow neck and exhibit rapid flow. Inferior wall pseudoaneurysms that
      develop soon after primary percutaneous intervention and coronary artery bypass
      grafting for acute myocardial infarction are rare. We report the case of a 64
      year-old man who had a wide-necked left ventricular inferior wall pseudoaneurysm
      that developed soon after surgery for an acute myocardial infarction and post
      infarction mitral regurgitation that occurred as a mechanical complication. The
      surgery consisted of coronary artery bypass grafting and mitral valve
      replacement. After the surgery, congestive heart failure developed. At
      reoperation, we found a large pseudoaneurysm that had caused tearing of the
      chordae tendineae of the posterior mitral leaflet and scarring around the
      inferior wall defect. The inferior wall defect had formed the wide neck of the
      left ventricular pseudoaneurysm. We excised the pseudoaneurysm and the scar
      tissue and attached a small patch to the defect such that it decreased the left
      ventricular dimension. Our patient survived the surgery and recovered completely.
      In patients with acute myocardial infarction, left ventricular pseudoaneurysms
      can occur soon after coronary artery bypass grafting and surgery for a
      complication such as mitral valve regurgitation. When a large portion of the left
      ventricular wall is infarcted and its removal would create a smaller cavity with
      compromised output, we recommend ventricular reconstruction by patch placement.

PMID- 17215983
TI  - Severe gastroparesis causing splenic rupture: a unique, early complication after
      heart-lung transplantation.
AB  - Several weeks or even months after heart-lung transplantation, gastroparesis-or
      delayed gastric emptying-commonly presents with cough, early satiety, and
      bloating. As it progresses, gastroparesis can cause substantial malnutrition and
      impair drug absorption. Gastroparesis after heart-lung transplantation can be
      attributed to bilateral vagus nerve injury, which probably occurs just above the
      level of the carina, where the recipient's trachea is resected. We report a
      highly unusual case wherein gastroparesis presented early after heart-lung
      transplantation and was managed conservatively. However, 19 days postoperatively,
      the patient developed acute abdominal pain and hypotension. Laparotomy revealed a
      massively dilated stomach and total avulsion of the splenic capsule with
      hemorrhage. The patient was fed via jejunostomy tubes until the gastroparesis
      resolved spontaneously. This case illustrates an important sequela of heart-lung
      transplantation. In order to decrease the morbidity from gastroparesis in these
      fragile patients, a drainage procedure should be considered as an adjunct to
      heart-lung transplantation.

PMID- 17215984
TI  - Acute myocardial infarction with normal coronary arteries in a patient with
      Hodgkin's disease: a late complication of irradiation and chemotherapy.
AB  - We describe the case of a 31-year-old man who experienced an acute myocardial
      infarction 16 years after undergoing radiation and vinca alkaloid therapy for
      Hodgkin's disease. Even though coronary artery disease is a well-established
      complication after mediastinal radiation therapy, this adult patient had normal
      coronary angiographic results, with no traditional risk factors for coronary
      artery disease, and no hematologic or other abnormality associated with
      hypercoagulability.

PMID- 17215985
TI  - Emergency stenting of unprotected left main coronary artery after acute catheter
      induced occlusive dissection.
AB  - Left main coronary artery dissection occurs very rarely during selective coronary
      angiography, but it generally progresses to complete coronary occlusion. The
      traditional treatment of occlusive dissection of the unprotected left main
      coronary artery has been surgical. Percutaneous treatment has been sporadic and
      controversial. We report a case of iatrogenic occlusive dissection of the
      unprotected left main coronary artery during diagnostic coronary angiography,
      followed by successful stenting of the lesion.

PMID- 17215986
TI  - Purulent pericarditis caused by group a streptococcus.
AB  - Purulent pericarditis is a rare disease that is most often caused by organisms
      such as Staphylococcus aureus, Streptococcus pneumoniae, viridans streptococci,
      Haemophilus influenzae, and anaerobic bacteria. We present an unusual case of
      purulent pericarditis caused by Streptococcus pyogenes, Lancefield group A
      streptococcus (GAS), and we provide a review of the literature.

PMID- 17215987
TI  - Free intra-abdominal hemorrhage after open-heart surgery: an unusual
      gastrointestinal complication.
AB  - Gastrointestinal complications after open-heart surgery are rare. Many
      preoperative, intraoperative, and postoperative factors may predispose patients
      to these complications or cause them. Our patient was a 64-year-old woman who
      underwent aortic valve replacement due to aortic stenosis. Free intra-abdominal
      hemorrhage occurred on the 2nd postoperative day. During exploratory laparotomy,
      it was determined that the hemorrhage was from a vein near the falciform ligament
      of the liver and from a bleeding laceration of the splenic capsule. The
      complication was repaired surgically. To our knowledge, intra-abdominal
      hemorrhage of both liver and spleen after open-heart surgery has never been
      reported before, even in large patient series. We report the case and present our
      ideas regarding the cause of the bleeding.

PMID- 17215988
TI  - Iatrogenic cardiac herniation and torsion after surgery for a penetrating cardiac
      injury.
AB  - Cardiac herniation and torsion is a rare condition associated with a high
      mortality rate. We present an unusual case of sudden cardiogenic shock that was
      caused by torsion and herniation of the heart after an operation for a
      penetrating cardiac injury. The patient was successfully treated by urgent
      surgical intervention.

PMID- 17215990
TI  - Acute massive pulmonary embolism after migration of an inferior vena cava filter
      to the right ventricle.

PMID- 17215989
TI  - Large annular subvalvular left ventricular aneurysm: diagnostic evaluation using
      computed tomographic angiography.

PMID- 17215991
TI  - Origin of the right pulmonary artery from the ascending aorta in a 25-year-old
      man.

PMID- 17215992
TI  - Diagnosis of Marfan syndrome by computed tomography.

PMID- 17215993
TI  - Are muscular bridges capable of causing myocardial infarction?

PMID- 17215995
TI  - Use of double wires in sternal closure: a useful technique.

PMID- 17215996
TI  - Update on the american urological association guidelines for the treatment of
      benign prostatic hyperplasia.
AB  - The updated 2003 American Urological Association (AUA) Guidelines for the
      treatment of benign prostatic hyperplasia (BPH) are the culmination of an
      exhaustive effort predicated on scientifically accepted methods of reviewing the
      medical literature. In this second publication of the guidelines, a
      multidisciplinary panel reviewed a new meta-analysis of outcome data from the BPH
      literature from before and after 1994. The major differences between the 2
      guidelines are the changes in our understanding of the biology of the prostate
      and the introduction of new therapies. The vast majority of randomized controlled
      trials, particularly with respect to minimally invasive therapies and progression
      of BPH, were performed after the release of the 1994 guidelines. Also, the most
      recent AUA panel carefully reviewed unpublished data to make the guidelines as
      timely as possible. Studies that were subsequently published included those on
      the value of combination medical therapy for BPH. The panel agreed on updated
      recommendations for the treatment of moderate-to-severe lower urinary tract
      symptoms associated with BPH, and diagnostic algorithms were revised. The
      durability and utility of the present guidelines should exceed that of its
      predecessor.

PMID- 17215997
TI  - Current concepts in ejaculatory dysfunction.
AB  - Although erectile dysfunction has recently become the most well-known aspect of
      male sexual dysfunction, the most prevalent male sexual disorders are ejaculatory
      dysfunctions. Ejaculatory disorders are divided into 4 categories: premature
      ejaculation (PE), delayed ejaculation, retrograde ejaculation, and
      anejaculation/anorgasmia. Pharmacologic treatment for certain ejaculatory
      disorders exists, for example the off-label use of selective serotonin reuptake
      inhibitors for PE. Unfortunately, the other ejaculatory disorders are less
      studied and not as well understood. This review revisits the physiology of the
      normal ejaculatory response, specifically explores the mechanisms of
      anejaculation, and presents emerging data. The neurophysiology of the ejaculatory
      reflex is complex, making classification of the role of individual
      neurotransmitters extremely difficult. However, recent research has elucidated
      more about the role of serotonin and dopamine at the central level in the
      physiology of both arousal and orgasm. Other recent studies that look at
      differing pharmacokinetic profiles and binding affinities of the alpha(1)
      antagonists serve as an indication of the centrally mediated role of ejaculation
      and orgasm. As our understanding of the interaction between central and
      peripheral modulations and regulation of the process of ejaculation increases,
      the probability of developing centrally acting pharmaceutical agents for the
      treatment of sexual dysfunction approaches reality.

PMID- 17215998
TI  - Alpha-blockers for the treatment of prostatitis-like syndromes.
AB  - Prostatitis is a common medical diagnosis. The etiology of this symptomatic
      syndrome can be an acute or chronic bacterial infection, a noninfectious
      initiator (the most common cause), or iatrogenic heat or radiation; the syndrome
      may coexist with benign prostatic hyperplasia. Alpha-blockers have a role in the
      treatment of the prostatitis syndromes. In Category I, acute bacterial
      prostatitis, alpha-blockers have been shown to possibly ameliorate obstructive
      and irritative voiding symptoms. In Category II, chronic bacterial prostatitis,
      alpha-blockers seem to reduce the risk of clinical and bacteriological
      recurrence. In Category III, chronic pelvic pain syndrome, alpha-blockers improve
      symptoms and quality of life. Alpha-blockers also seem to ameliorate the symptoms
      and reduce the risk of acute urinary retention in patients who suffer from either
      heat- or radiation-induced prostatic inflammation. Alpha-blockers improve lower
      urinary tract symptoms, including pain, in patients who are diagnosed with both
      prostatitis and benign prostatic hyperplasia. Evidence has proven there is
      definitely a role for alpha-blockers in the management of the prostatitis
      syndromes.

PMID- 17215999
TI  - The evolution of alpha-blockers for the treatment of benign prostatic
      hyperplasia.
AB  - Alpha-blockers have been evaluated for the treatment of benign prostatic
      hyperplasia (BPH) for 30 years, from early trials with the nonselective alpha
      inhibitor phenoxybenzamine to short-acting (prazosin) then long-acting
      (terazosin, doxazosin, tamsulosin, alfuzosin) selective alpha(1)-antagonists. All
      of the alpha-blockers evaluated have demonstrated comparable effectiveness, and
      the evolution of alpha-blocker therapy for BPH has therefore focused primarily on
      improving convenience and tolerability. Although all of the long-acting alpha(1)
      blockers are well tolerated, only tamsulosin and alfuzosin SR are administered
      without the requirement for dose titration. Alfuzosin has the additional
      advantage over tamsulosin of a lower incidence of ejaculatory dysfunction.
      Studies of subtype-selective alpha(1)-antagonists have not demonstrated superior
      efficacy or improved tolerability over the existing long-acting alpha(1)
      blockers.

PMID- 17216000
TI  - The use of alpha-blockers for the treatment of nephrolithiasis.
AB  - Medical expulsion therapy has been shown to be a useful adjunct to observation in
      the management of ureteral stones. Alpha-1-adrenergic receptor antagonists have
      been studied in this role. Alpha-1 receptors are located in the human ureter,
      especially the distal ureter. Alpha-blockers have been demonstrated to increase
      expulsion rates of distal ureteral stones, decrease time to expulsion, and
      decrease need for analgesia during stone passage. Alpha-blockers promote stone
      passage in patients receiving shock wave lithotripsy, and may be able to relieve
      ureteral stent-related symptoms. In the appropriate clinical scenario, the use of
      alpha-blockers is recommended in the conservative management of distal ureteral
      stones.

PMID- 17216001
TI  - [Reclassification of gastrointestinal mesenchymal tumors].
AB  - A retrospective (1985-2005) multicentric evaluation of the pathological diagnoses
      of GIST (gastrointestinal stromal tumor) in Hungary was performed. A large cohort
      of 463 patients with abdominal mesenchymal tumors was reevaluated with the help
      of immunohistochemistry for CD117, CD34, desmin and S100. Prognostic groups have
      been established based on international criteria. Two hundred fifty five GISTs
      have been found in 245 patients during the evaluated period. Beside GIST, 81
      leiomyogenic and 25 neurogenic tumors were the primary pathological diagnosis and
      in 74/255 cases the primary diagnosis was a benign tumor. In our cohort high-risk
      GIST cases were found to be the predominant. Based on our experience, in case of
      abdominal tumors of uncertain localization, immunohistochemical markers of CD117,
      CD34, S100 and desmin provide a proper tool for precise identification of the
      tumor entity including GIST.

PMID- 17216002
TI  - [Trastuzumab (Herceptin) in the adjuvant treatment of HER-2-positive early breast
      cancer].
AB  - The prognosis of HER-2-positive breast cancer (characterized by amplification of
      the HER-2 oncogene and/or overexpression of HER-2 receptor) is unfavourable.
      Trastuzumab (Herceptin), a monoclonal antibody against HER-2 receptor can improve
      the outcome of HER-2-positive breast cancer. Up to now this was proven only in
      advanced disease. Recently five large multicentric phase III adjuvant trials gave
      level one evidence on the benefit of adjuvant treatment with Herceptin,
      concerning disease-free survival (DFS) and overall survival (OS). Herceptin has
      decreased the relative risk of recurrence with about 50% and that of death with
      nearly 30% in HER-2-positive early breast cancer. Based on these results
      Herceptin, together with chemotherapy, has been recently approved for the
      adjuvant treatment of HER-2-positive breast cancer.

PMID- 17216003
TI  - [Complex treatment of inflammatory breast cancer].
AB  - Inflammatory breast cancer represents 2-5% of all malignant breast lesions. Its
      rapid progression, the rather short medical history of the disease is unique and
      seems to be very typical. The combined modality treatment of inflammatory breast
      cancer is a special challenge for the medical oncologists. Preoperative
      chemotherapy is of great importance. After getting fair remission, surgery and
      radiotherapy should be delivered. With combined modality therapy the 5-year
      overall survival is about 50%. Knowing more pharmaco-genomic details on the
      disease and delivering new medicaments the effectiveness of the treatment will be
      further enhanced.

PMID- 17216004
TI  - [Molecular pathology and targeted therapy of clear cell renal cancer].
AB  - The golden standard of care for advanced renal cell cancer (RCC) was until now
      the cytokine therapy with relatively low response rates. Advances of molecular
      genetics in RCC revealed several molecular targets such as VHL and angiogenic
      genotype or EGFR in the clear cell variant. Among the novel targeted agents,
      multiple tyrosine kinase inhibitors were proved to be clinically effective
      against advanced clear cell renal cancer, changing the standard of care. It is a
      further question how molecular diagnostics can improve these results by the
      detection of these targets or gene defects in individual tumors.

PMID- 17216005
TI  - [Chemotherapy agents, response rates and mechanisms of resistance in the therapy
      of the colorectal carcinoma].
AB  - Colorectal carcinoma is one of the most common cancers in Hungary, responsible
      for about 5000 deaths each year. In the first line treatment the most commonly
      used drugs are 5-fluorouracil, oxaliplatin and irinotecan. The most frequently
      used drug is 5-fluorouracil, which has no effect in 90% of the cases. In
      combination with leukovorin or with 5-ethyl-2'-deoxyuridin fluorouracil has an
      increased effect. The main mechanisms of the resistance against 5-fluorouracil
      are due to the overexpression of dihydropyrimidine dehydrogenase, MRP8,
      thymidylate synthase, and NFkB p65. Oxaliplatin forms reactive platinum
      complexes, which are believed to inhibit DNA synthesis by forming interstrand and
      intrastrand cross-linking of DNA molecules. The oxaliplatin-5-fluorouracil
      leucovorin combination was the first to reach more than 20 months median
      survival. The main mechanisms of resistance are decreased accumulation, increased
      detoxification and increased DNA repair. Irinotecan inhibits the topoisomerase I
      enzyme, resulting in the inhibition of the repair of DNA breaks occurring during
      DNA synthesis. With sequential 5-fluorouracil, oxaliplatin, irinotecan
      combination 26 months median survival was reached. Mechanisms resulting in
      resistance are decreased accumulation, increased enzymatic detoxification,
      alterations of ABC transporters, DNA repair system, apoptotic pathways and
      topoisomerase I. Survival can be elongated using biological therapy (cetuximab,
      bevacizumab). In the near future biological therapy is expected to spread.

PMID- 17216006
TI  - [The role of ibandronate in the daily oncological practice].
AB  - Intravenous ibandronate at a dose of 6 mg every 3-4 weeks in patients with breast
      cancer and bone metastases produced a significant, 40% reduction in the relative
      risk of skeletal-related events. Oral ibandronate at a dose of 50 mg once daily
      for 96 weeks similarly reduced the overall skeletal morbidity, equating to a
      reduction in the relative risk of skeletal-related events of 38% relative to
      placebo. Ibandronate was generally well tolerated in clinical trials and their
      long-term extensions. Both type of administration significantly improve patients'
      health-related quality of life. There was no evidence of renal toxicity with iv.
      or oral ibandronate.

PMID- 17216007
TI  - [Detection of late ototoxic side effect of cisplatin by distortion otoacoustic
      emission (DPOAE)].
AB  - Cisplatin-based chemotherapy results in high cure rate in testicular cancer. The
      issue of toxicity is of special concern in young men with a probability of cure
      of at least 70-80% even in disseminated disease. As the literature shows, the
      ototoxic side effects of cisplatin have been studied mostly by conventional
      method. The authors used distortion product otoacoustic emission to detect the
      long-term ototoxic effect of cisplatin in 223 patients with a median follow-up
      time of 4.27 years (range 0.5-20 years) and a median age of 37 years (range 18-55
      years). Cisplatin (20 mg/m(2) body surface) was administered for five days per
      cycle, in combination with other antitumor drugs. The control group consisted of
      40 testicular cancer patients who did not receive chemotherapy, with a median age
      of 35 years (range 16-54 years). A detailed medical history based on a
      standardized questionnaire evaluated hearing complaints and audiological risk
      factors, such as head injuries, chronic otitis media, previous noise exposure and
      familial hearing loss. DPOAE was measured at 8 frequencies from 750 to 8000 Hz.
      No amplitude changes were detected in patients receiving =300 mg/m(2) cisplatin.
      At higher doses, contrary to the literature, not only high frequencies were
      affected: our method could detect significant hearing impairment at lower
      frequencies important for speech perception in patients receiving at least 400
      mg/m(2) cisplatin. The lower frequencies where significant amplitude changes were
      detected were 3000 Hz at 400 mg/m(2), and 1500, 2000 and 3000 Hz at 500-600
      mg/m(2). We detected the worst hearing in the case of patients who had
      symptomatic ototoxicity. Age and the cumulative dose of cisplatin proved
      statistically significant risk factors, while smoking or noise exposure did not
      have predictive value. As a conclusion, DPOAE is a fast, noninvasive and reliable
      method for the detection of late ototoxicity in testicular cancer patients. In
      our study hearing loss correlated with the cumulative dose of cisplatin. Hearing
      impairment contributes to the already compromised situation of cancer patients.

PMID- 17216008
TI  - [In vivo mutagenicity of the carcinogenic 1-nitropyrene. A model of a potential
      asbestos exposure].
AB  - The environmental carcinogen 1-nitropyrene was orally and intraperitoneally
      administered to rats in a single dose of 30 mmol/kg. Mutagenicity of excreted
      urine was tested in Salmonella typhimurium TA 98 and 100 strains. The mutagenic
      pattern of urine in case of oral exposure proved to be completely different as
      compared to the intraperitoneal administration. Frame-shift mutagen(s) was/were
      detected only after enzymatic deconjugation of sulphate or glucuronide
      metabolites within the first 24 h. Base-pair substitution-type mutagenicity was
      only detected in the urine samples collected after intraperitoneal treatment.
      Since environmental asbestos exposure involves carcinogenic effects of adsorbed
      polycyclic aromatic hydrocarbons, this animal model provides a useful tool for
      testing fiber-associated nitroarenes, in both mechanistic and risk assessment
      studies.

PMID- 17216009
TI  - [New radiotherapeutic technique for application of craniospinal target volume].
AB  - AIM: To work out a craniospinal target volume definition and radiotherapy which
      can be used in clinical practice. METHOD: This technique has been applied in the
      Municipal Center of Oncoradiology since 2004 for total cerebral and spinal
      (neuroaxis) radiation. The individual radiation treatment plans were carried out
      using the CadPlan (Varian) 3D planning system with linear accelerator, in 3D on
      the basis of CT. The CT slices were prepared at 1 cm distance. The target volume
      and the organs at risk (OAR) were marked in slices. To delineate the field
      asymmetrical blending and multileaf collimator (MLC) were applied. Depending on
      the shape and size of the target, two or more field matching were made with the
      new technique. RESULTS: The dose distribution in the target volume and the OAR
      were controlled in the coronary, sagittal and horizontal views and with dose
      volume histograms (DVH). CONCLUSIONS: The condition for applying this technique
      is the accurate adjustment of digital simulator picture, field-control picture
      and DRR (digital reconstructed radiogram).

PMID- 17216010
TI  - [Primary gastrointestinal stromal tumor of the mesentery].
AB  - Primary solid tumors of the mesentery are very rare. The authors found a bulky
      gastrointestinal stromal tumor (GIST) in the mesentery. The stomach and the
      intestines were tumor-free.

PMID- 17216012
TI  - [Does magnetic resonance represent the future in the follow-up of arthritis?].
AB  - Several studies suggest that MRI is between 2 and 10 times superior to
      conventional radiology in the visualization of erosions. This higher sensibility
      is dependent on the specific joint assessed, the precocity of the disease, and
      the timing of follow-up. In addition, MRI can depict bone oedema, which is an
      early and reversible bone lesion, and evaluate the degree of inflammation of the
      synovial membrane. A single examination could therefore evaluate disease activity
      and damage. The sensitivity to change of articular MRI is good, as demonstrated
      by a number of follow-up studies. In view of these advantages, it may be
      surprising that MRI has not yet become the gold standard of imaging of the
      arthritic joint. The three main reasons are low availability of high field
      machines, examination's costs, and lack of standardization of the technique. Low
      field extremity-dedicated MRI machines are probably the answer to the first two
      concerns. They have been shown to obtain reliable results for the clinician, and
      to be relatively cheap and patient-friendly, allowing repeated follow-up
      examinations. As far as standardization is concerned, there are many studies
      addressing the problem, with OMERACT as the driving force. MRI is likely to
      represent the future of the follow up of arthritis for the evaluation of its pace
      of progression and the effect of treatment. The advent of new and potent biologic
      therapies has incremented the need for more sensible imaging methods and will
      probably drive their diffusion in clinical practice.

PMID- 17216011
TI  - [Developments in cancer management by innovative genomics. 2006 report of the
      National Cancer Consortium].
AB  - Research on developing molecular diagnostics for hereditary cancers resulted in
      establishing diagnostic services for familiar polyposis and non-polyposis
      patients (mutation determination of APC, MYH, STK11, SMAD4, MLH1, MSH2). In
      familiar testicular cancers the role of gr/gr gene on Y chromosome was
      identified. Molecular diagnostic tool was established to monitor the progression
      of follicular lymphoma using Bcl-2/IgH fusion sequences. Molecular diagnostic
      tools were developed to monitor circulating endothelial precursor cells (CEP) as
      well and the technique was tested in lung cancer patients. In malignant melanoma
      we have tested several potential novel markers among which ryanodine receptor
      seems to be a promising one, while the functional P2X7 receptor may serve as a
      therapeutic target. We have determined the tyrosine kinase "kinome" profile of
      HER-2-amplified breast cancers. Furthermore, the "kinome" profile was found to be
      characteristic for head and neck cancers of various anatomical location. Based on
      previous studies on the anti-migratory and antimetastatic potential of low
      molecular-weight heparins, we have identified short heparin-derived
      oligosaccharides with maintained antimetastatic- but non-anticoagulant
      potentials. Pharmacogenomic studies on the role of polymorphism of the serine
      hydroxymethyl-transferase (SHMT) gene in the efficacy of 5-FU and FOLFIRI
      protocols of colorectal cancer patients revealed a significant effect resulting
      in altered overall survival as well.

PMID- 17216013
TI  - [Improvements in the management of rheumatic patients from vertebral image
      obtained through dual-energy X-ray absorptiometry].
AB  - The diagnosis of asymptomatic vertebral fracture is clinically useful and the
      identification of new fractures may influences the choice of appropriate
      therapeutic measures. In order to identify moderate and asymptomatic vertebral
      deformities in an objective and reproducible manner, vertebral morphometry is
      performed. This method measures the vertebral body's anterior, middle and
      posterior heights at the dorsal and lumbar level. Currently this technique is
      performed on lateral images of the spine obtained through the traditional X-ray
      method (radiological morphometry or morphometric X-ray radiography, MRX) and,
      more recently from images obtained through dual-energy X-ray absorptiometry (DXA)
      machines (visual assessment of X-ray absorptiometry scans or morphometric X-ray
      absorptiometry, MXA), commonly used to measure bone mineral density. The main
      advantage of MXA relative to MRX is the lower radiation dose to which the patient
      is exposed during the exam. In addition, MXA scans offers the advantage of
      acquiring a single image of thoracic and lumbar spine, without any distortion
      (e.g.: coning). The most obvious advantage of MXA is the opportunity of obtaining
      during the same session a bone mineral density evaluation, and digital images
      that are easily processable, manageable, recordable and comparable for the
      patient's follow up. A limitation of the MXA technique is the inferior quality of
      the images, that make often impossible the detection of the vertebral edges, and
      the impossibility to visualize the upper thoracic vertebral bodies. MXA, despite
      its intrinsic limitations, when carried out by trained personnel may provide
      substantial improvements in the management (diagnosis and follow-up) of rheumatic
      patients.

PMID- 17216014
TI  - [Safety of methotrexate in rheumatoid arthritis: a retrospective cohort study in
      clinical practice].
AB  - OBJECTIVE: To evaluate the treatment duration with MTX monotherapy or in
      association with DMARDs or TNFalpha inhibitors and the incidence and typology of
      adverse events (AE) occurred in rheumatoid arthritis (RA) patients. METHODS: A
      retrospective large cohort study of RA outpatients, consecutively seen from
      January 2000 to June 2005 was performed. Study group were RA patients classified
      according to the 1984 ACR criteria for the classification of rheumatoid
      arthritis. The patients were divided in 3 groups according to the treatment
      regimen: MTX monotherapy, MTX in combination with DMARD or with anti TNFalpha
      agents. We analyzed 348 therapeutic cycles, 177 of whom using MTX monotherapy.
      RESULTS: The 224 RA patients accumulated 800 person-years of follow up. Follow up
      for each of the groups was: MTX monotherapy 479.4 person-years, MTX in
      combination with DMARDs 244.5, or with TNFalpha inhibitors, 75.7 person-years.
      From the Kaplan-Meier analysis, the probability of patients remaining on
      treatment 5 years was 58.5 after starting MTX. The incidence of any AE was 8.87
      per 100 person-years. From all, 69 (97.2%) AE were no severe. Among those, more
      frequently were observed at gastrointestinal tract (31%), liver (19.7%), skin
      (15.5%). Incidence of severe AE (lung adenocarcinoma, 1 case; pancreatitis, 1
      case) was 0.25 per 100 person-years, occurring in patients taking MTX monotherapy
      or MTX in combination with DMARDs, respectively. CONCLUSIONS: These data confirm
      that methotrexate is well tolerated in clinical practice in the medium-long term.
      Nevertheless, the occurrence of severe AE require an accurate vigilance for
      methotrexate toxicity.

PMID- 17216015
TI  - [Intra-articular treatment with the TNF-alpha antagonist, etanercept, in severe
      diffuse pigmented villonodular synovitis of the knee].
AB  - Pigmented villonodular synovitis (PVNS) is a rare pre-malignant disease that
      require aggressive treatment as surgical synovectomy, eventually followed by
      radiosynovectomy. Nevertheless, the disease often reoccurs after these
      treatments. To determine the safety and efficacy of intra-articular (IA) TNFalpha
      blockade with etanercept (ETN), before extended arthroscopic synovectomy, in
      severe PVNS of the knee, two patients, (a 26-year-old man with B27+
      undifferentiated spondylarthropathy and a 32-year-old femal with seronegative
      oligoarthritis), affected by diffuse knee PVNS (diagnosis made by histological
      examination), resistant to IA corticosteroid injections and to repeated
      arthroscopic synovectomy, were submitted, after protocol approval by human
      research committee and patient's written informed consent to intra-articular
      etanercept (IA-ETN) treatment with a different dosage schedule: 12.5 mg weekly IA
      ETN injection for 4 weeks, followed by extended arthroscopic synovectomy and of
      25 mg IA-ETN injection for 4 weeks, respectively. Previous DMARDs treatment was
      continued in stable appropriate doses. Any adverse events were recorded
      throughout the study. The following parameters were considered as clinical
      endpoints: 1) Knee Joint Index (KJI: range 0-14); 2) Thompson index (THI: range 0
      9) At the study entry and at the end of follow-up, high frequency ultrasound grey
      scale synovial thickening (US-ST) was also assessed. No adverse events were
      observed due to IA-ETN and to arthroscopic synovectomy. Marked improvement of
      knee disease activity over time and sustained functional recover was obtained. US
      ST evaluation before treatment initiation and at the end of follow-up confirmed
      the regression of knee joint synovial proliferation.

PMID- 17216016
TI  - [TNF-alpha inhibition in anti-Ro/SSA positive patients with rheumatoid arthritis:
      clinical and immunologic effects].
AB  - OBJECTIVE: To analyse efficacy and safety of anti-TNFalpha treatment in 17
      patients with rheumatoid arthritis (AR) and anti-Ro antibodies, in order to
      detect difference in clinical and immunological response. METHODS: 322 patients,
      affected by RA and treated with anti-TNFalpha drugs, were considered, searching
      every 6-12 months ANA, anti-dsDNA and anti-ENA antibodies. Seventeen were anti-Ro
      positive and 305 anti-Ro negative before starting treatment. RESULTS: Anti-Ro
      positive subjects showed active arthritis at baseline (mean DAS: 5), with
      frequent extra-articular features, such as ocular and oral sicca symptoms. They
      showed rapid and stable improvement during the treatment, with-out significant
      difference compared to anti-Ro negative group. A good clinical Eular response was
      shown in 46% of anti-Ro negative subjects, steady stable during time. On the
      contrary, fewer anti-Ro positive patients seem to be "good" responders. RA
      remission (DAS <1,6) was achieved in 9-25% of anti-Ro positive and 21-29% of anti
      Ro negative, without significant difference. Antinuclear antibodies tend to
      increase in both groups, during the time. Anti-DNA increased to 40% of anti-Ro
      positive sera since 6th month, while they slightly increased in first 12 months
      in anti-Ro negative ones, then decreased to baseline value. No differences were
      shown about the frequency and reasons of anti-TNFalpha withdrawal, except for
      cutaneous lupus-like disease, more detected in anti-Ro positive group.
      CONCLUSIONS: Anti-TNFalpha drugs are effective in anti-Ro positive RA as well as
      other RA patients. Anti-DNA positivity and lupus-like disease were more
      frequently observed in anti-Ro positive group.

PMID- 17216017
TI  - [Primary antiphospholipid syndrome and hyperhomocysteinemia: a study of a group
      of 29 patients].
AB  - OBJECTIVE: In order to investigate the potential role of hyperhomocysteinemia as
      an additional risk factor for thrombotic events, we studied its prevalence in
      patients with primary antiphospholipid syndrome (APS) and evaluated its
      association with different clinical features. METHODS: We enrolled 29 patients
      without any current evidence of underlying connective tissue disorder and
      fulfilling the Sapporo preliminary classification criteria for APS. RESULTS: Ten
      (34,4%) patients showed mild hyperhomocysteinemia (18,34 micromol/L +/- 2,04 DS).
      Nine had history of cerebrovascular disease, isolated (3 cases) or more often (6
      cases) in association with other APS features. All patients, but one, showed
      multiple ischemic cerebral lesions. Seven of the 10 patients with
      hyperhomocysteinemia had multiple antiphospholipid antibody positivity and
      presented more frequently (6 cases) multi-site vascular involvement. CONCLUSIONS:
      The frequency of hyperhomocysteinemia in patients with primary APS is not
      negligible and appears to be associated with cerebral microangiopathic disease,
      multiple antiphospholipid antibody positivity and the simultaneous involvement of
      different vascular districts. For this reason and because hyperhomocysteinemia
      can be easily corrected with safe and relatively inexpensive therapeutic
      interventions, we advocate the measurement of homocysteinemia in every patient
      affected by APS and possibly in subjects with positive antiphospholipid antibody
      without a history of thrombosis.

PMID- 17216018
TI  - [Anabolic effects and inhibition of interleukin 6 production induced by
      neridronate on human osteoblasts].
AB  - Bisphosphonates (BPs) are pharmacological compounds widely used in the treatment
      of a variety of bone-related diseases, particularly where the bone-turnover is
      skewed in favour of osteolysis. The mechanisms by which BPs reduce bone
      resorption directly acting on osteoclasts (OCs) are now largely clarified even at
      molecular level. The researches concerning the BPs effects on osteoblasts (OBs)
      have instead shown variable results. OBJECTIVES: We have investigated the
      efficacy of neridronate (NER), an amino-BP, as anabolic agent on human OBs.
      Moreover, we have tried to verify if NER is able to negatively modulate the
      production of IL-6 on OBs stimulated or not by the pro-inflammatory cytokine IL
      1beta. METHODS: We have tested if different concentrations of NER (from 10-11 M
      to 10-3 M), added to primary human OB cultures, could affect the cells number,
      the endogenous cellular alkaline phosphatase (ALP) activity, the collagen I (COL
      I) synthesis, the formation of mineralized nodules and the IL-6 production. Our
      experimental approach was performed testing a wide range of NER concentrations
      because, under physiological conditions, OBs seems to be exposed to variable and
      transient levels of the drug. RESULTS: Our results show that NER doesn't
      negatively affect in vitro the viability, proliferation and cellular activity of
      human OBs, even after 20 days of exposure to concentrations < or =10-5 M
      (therapeutic dose). In addition, NER seems to enhance the differentiation of
      cultured OBs in mature bone-forming cells. A maximum increase of COL-I synthesis
      (+25% after 4 days; p < 0.05), ALP activity (+50% after 10 days; p < 0.01) and
      mineralized nodules (+48% after 20 days; p < 0.05) was observed in cultures
      treated with NER 10-8 M. A maximal reduction of IL-6 secretion (-24% on IL-1beta
      stimulated cultures and -29% on unstimulated cultures) was observed for NER 10-9
      M. CONCLUSIONS: These results encourage the use of neridronate in therapy of
      demineralizing metabolic bone disorders.

PMID- 17216019
TI  - [Italian consensus on EULAR recommendations 2005 for the management of hip
      osteoarthritis].
AB  - The recommendations for the management of osteoarthritis (OA) of the hip were
      proposed by EULAR in 2005. Among the most important objectives of the expert
      charged to provide these recommendations were their wide dissemination and
      implementation. Thus, the information generated can be used by each individual
      country to produce their own set of management guidelines and algorithms for
      treatment in primary care. According with that previously executed for the EU-LAR
      recommendation 2003 for the knee, the Italian Society of Rheumatology (SIR) has
      organised a Consensus on the EULAR recommendations 2005 for the management of hip
      OA. To obtain an acceptability as large as possible, the group of experts was
      composed by many physicians interested in the management of hip OA, including
      Orthopaedics, Rheumatologists, Physiatrists, and General Practitioners. Main aim
      of the Consensus was to analyse the acceptability and applicability of the
      recommendations according to own experience and local situations in the Italy.
      The results of this Consensus have demonstrated that a large majority of the
      EULAR recommendations are endorsed by the Italian experts. Furthermore, the final
      document of the Italian Consensus clearly indicated the need that the specialists
      involved in the management of hip OA strongly encourage the dissemination of the
      EULAR 2005 recommendations also in Italy.

PMID- 17216020
TI  - [Buschke Scleredema, case report].
AB  - Buschke Scleredema is a rare connective tissue disorder of unknown aetiology,
      characterized by thickening of the dermis whose characteristics may mainly to
      mime systemic sclerosis, eosinophilic fasciitis and cutaneous amyloidosis.
      Scleredema may be associated with a history of an antecedent febrile illness,
      diabetes mellitus, or blood dyscrasia. Scleredema can be classified into three
      clinical groups; each has a different history, course, and prognosis. Each one of
      these share reduction in chest articular movements and limitation of limbs
      movements. The skin histology is characterised by thickened dermis and increased
      spaces between large collagen bundles due to increased deposition of
      mucopolysaccharide in the dermis. Differential diagnosis can be made considering
      the typical clinical features and the histologic peculiarity. No therapy has been
      found effective. The authors describe a case of Buschke Scleredema successfully
      treated by steroids and colchicine. Clinical evaluation of skin induration and
      thickness as well as ultrasonography were performed at baseline and after
      treatment.

PMID- 17216021
TI  - [Study of vitamin D status of rheumatoid arthritis patients. Rationale and design
      of a cross-sectional study by the osteoporosis and metabolic bone diseases study
      group of the Italian Society of Rheumatology (SIR)].
AB  - The fundamental role of Vitamin D has been long known in regulating calcium
      homeostasis and bone metabolism. An increased contribution of Vitamin D was
      recently described in association with a lower incidence of Rheumatoid Arthritis
      (RA). This must not be surprising, as the immunomodulating effects of Vitamin D
      are clear, which have been attributed protective effects in autoimmune disorders
      such as some chronic inflammatory bowel diseases, multiple sclerosis and type I
      diabetes. An interaction was suggested between Vitamin D metabolism and
      inflammation indexes through mediation of TNF-alpha which is also especially
      involved in osteoclastic resorption and therefore in bone loss processes. Some
      preliminary data would indicate an association between seasonal changes of
      Vitamin D serum levels, latitude and disease activity (DAS28) in RA patients.
      Consequently, the Osteoporosis and Metabolic Bone Diseases Study Group of SIR
      believes that there are grounded reasons for assessing the Vitamin D status of RA
      patients in order to investigate whether this is to be related to
      physiopathological and clinical aspects of disease other than those of bone
      involvement. Primary end point of the study will be to assess the levels of 25 OH
      Vitamin D in RA patients. Secondary endpoints will include correlation with dis
      ease activity, densitometry values and bone turnover. The cross-sectional study
      will enroll patients of both sex genders, age ranging between 30 and 75 years
      according to the 1988 ACR criteria, onset of symptoms at least 2 years prior to
      study enrollment. Patients will be excluded suffering from osteo-metabolic
      diseases, liver and kidney insufficiency and those administered Vitamin D boli in
      the previous 12 months. Disease activity will be evaluated with the HAQ. Hemato
      chemical tests and femoral and lumbar bone densitometry will be performed, unless
      recently undergone by patients. Blood levels of 25 OH C Vitamin D and PHT and of
      the two bone remodelling markers (bone alkaline phosphatase and serum CTX) will
      be measured, as well. Patient enrollment will start on February 2007 and will
      last 4 months. By the end of 2007 the study will be concluded and results will be
      published.

PMID- 17216022
TI  - [Filippo Civinini (1805-1844) and the discovery of plantar neuroma].
AB  - Pathological abnormality (neuroma) related to the painful foot condition commonly
      called "Morton's metatarsalgia" was first observed in 1835 by Filippo Civinini
      (1805-1844) of Pistoia, in course of a cadaverous dissection, and clearly
      described in the anatomic letter entitled "Su un nervoso gangliare rigonfiamento
      alla pianta del piede" ("On the neural ganglion swelling of the foot sole"). In
      this study a brief review on the history of Morton's metatarsalgia is carried
      out, and the importance of Civinini in the discovery of the neuroma of the III
      intermetatarsal web is underlined.

PMID- 17216026
TI  - Progress towards the easier use of P450 enzymes.
AB  - The cytochrome P450 enzymes (P450s or CYPs) form a large family of heme proteins
      involved in drug metabolism and in the biosynthesis of steroids, lipids, vitamins
      and natural products. Their remarkable ability to catalyze the insertion of
      oxygen into non-activated C-H bonds has attracted the interest of chemists for
      several decades. Very few chemical methods exist that directly hydroxylate
      aliphatic or aromatic C-H bonds, and most of them are not selective or of limited
      scope. Biocatalysts such as P450s represent a promising alternative: however,
      their applications have been limited by substrate specificity, low activity, poor
      stability and the need for cofactors. This review covers the attempts to overcome
      these limitations using approaches such as mutagenesis, chemical modifications,
      conditions engineering and immobilization.

PMID- 17216027
TI  - Protein detection using biobarcodes.
AB  - Over the past 50 years the development of assays for the detection of protein
      analytes has been driven by continuing demands for higher levels of sensitivity
      and multiplexing. The result has been a progression of sandwich-type
      immunoassays, starting with simple radioisotopic, colorimetric, or fluorescent
      labeling systems to include various enzymatic or nanostructure-based signal
      amplification schemes, with a concomitant sensitivity increase of over 1 million
      fold. Multiplexing of samples and tests has been enabled by microplate and
      microarray platforms, respectively, or lately by various molecular barcoding
      systems. Two different platforms have emerged as the current front-runners by
      combining a nucleic acid amplification step with the standard two-sided
      immunoassay. In both, the captured protein analyte is replaced by a multiplicity
      of oligonucleotides that serve as surrogate targets. One of these platforms
      employs DNA or RNA polymerases for the amplification step, while detection is by
      fluorescence. The other is based on gold nanoparticles for both amplification as
      well as detection. The latter technology, now termed Biobarcode, is completely
      enzyme-free and offers potentially much higher multiplexing power.

PMID- 17216028
TI  - Recent developments in the mechanistic enzymology of the ATP-dependent Lon
      protease from Escherichia coli: highlights from kinetic studies.
AB  - Lon protease, also known as protease La, is one of the simplest ATP-dependent
      proteases that plays vital roles in maintaining cellular functions by selectively
      eliminating misfolded, damaged and certain short-lived regulatory proteins.
      Although Lon is a homo-oligomer, each subunit of Lon contains both an ATPase and
      a protease active site. This relatively simple architecture compared to other
      hetero-oligomeric ATP-dependent proteases such as the proteasome makes Lon a
      useful paradigm for studying the mechanism of ATP-dependent proteolysis. In this
      article, we survey some recent developments in the mechanistic characterization
      of Lon with an emphasis on the utilization of pre-steady-state enzyme kinetic
      techniques to determine the timing of the ATPase and peptidase activities of the
      enzyme.

PMID- 17216029
TI  - Fluorescent reagents for in vitro studies of lipid-linked steps of bacterial
      peptidoglycan biosynthesis: derivatives of UDPMurNAc-pentapeptide containing d
      cysteine at position 4 or 5.
AB  - UDPMurNAc-L-Ala-gamma-D-Glu-X-D-Ala-DAla (X = L-Lys or m-DAP) is the cytoplasmic
      precursor for the lipid-linked cycle of bacterial peptidoglycan biosynthesis,
      consisting of at least four enzymatic reactions, which are targets for
      antibacterial agents. Fluorescent derivatives of the UDPMurNAc-pentapeptide
      labelled at the 3rd, 4th, and 5th position of the peptide chain were prepared
      chemoenzymatically, in order to study the reactions catalysed by enzymes in this
      cycle. Derivatives labelled on the epsilon-amino group of the 3rd amino acid (N
      dansyl, N-fluorescamine and N-phthalaldehyde) were prepared by chemical
      modification. Two methods were developed for preparation of analogues of
      UDPMurNAc-pentapeptide containing D-cysteine at position 4 or 5: either by MurF
      catalysed ligation of the UDPMurNAc-tripeptide to synthetic D-Ala-D-Cys or D-Cys
      D-Ala dipeptides; or by enzymatic synthesis of D-Ala-D-Cys by ligase VanD. D-Cys
      containing UDPMurNAc-pentapeptides were labelled with pyrene maleimide, to give 4
      pyrene and 5-pyrene labelled derivatives. The fluorescent UDPMurNAc-pentapeptides
      were processed as substrates by Escherichia coli MraY or E. coli membranes,
      giving 1.5-150-fold changes in fluorescence upon transformation to lipid
      intermediate I. Subsequent processing to lipid intermediate II gave rise only to
      small changes in fluorescence. Pyrene-labelled lipid intermediates I and II can
      be generated using Micrococcus flavus membranes, enabling the study of the later
      lipid-linked steps.

PMID- 17216031
TI  - Translating peptides into small molecules.

PMID- 17216030
TI  - A red-fluorescent substrate microarray for lipase fingerprinting.
AB  - A lipase substrate microarray was obtained by printing aliphatic C2-C12
      monoesters of (5R)- and (5S)-3-(5,6-dihydroxyhexyloxy)benzaldehyde by reductive
      alkylation on amine-functionalized glass slides coated with bovine serum albumin
      and a short PEG linker. The microarray features 12 substrates and their 66
      possible binary mixtures spotted in a 9 x 36 spot array. Lipase reactions are
      detected by chemoselective NaIO(4)-oxidation of the 1,2-diol hydrolysis product
      to form an aldehyde, which is then tagged with the red-fluorescent dye rhodamine
      B sulfohydrazide . Specific fingerprints are produced by active enzymes. These
      experiments provide the first example of lipase fingerprinting using microarrays.

PMID- 17216033
TI  - Commercial potential of RNAi.
AB  - The commercial potential of RNAi is assessed on the basis of successful
      translation of technology into applications in three areas: (1) drug discovery
      and research-currently the biggest segment; (2) potential therapeutic
      applications; and (3) the role of microRNA in molecular diagnostics. RNAi is an
      important method for analyzing gene function and identifying new drug targets
      that use dsRNA to knock down or silence specific genes. Sets of siRNAs focused on
      a specific gene class (siRNA libraries) have the capacity to greatly increase the
      pace of pathway analysis and functional genomics. RNAi plays an important role in
      drug discovery by facilitating target validation. The discovery of the role of
      microRNA (miRNAs) in various pathological processes opens up possible
      applications in molecular diagnostics, particularly that of cancer. The
      advantages of RNAi-based therapeutics over traditional pharmaceuticals include
      the capability for more specific therapies with small molecule siRNA. Drawbacks
      include the development of resistance in cancer and viral infections as well as
      the interferon effect. RNAi is closely related to gene therapy and the vectors
      developed for gene therapy are also being used for delivery of siRNAs. RNAi,
      along with other related technologies, will contribute to the development of
      personalised medicine. Although none of the RNAi-based drugs is in the market
      yet, some are in clinical trials. By the year 2010 the market for RNAi-based
      drugs is expected to be worth 3.5 billion dollars and is expected to expand to
      10.5 billion dollars by the year 2015.

PMID- 17216034
TI  - Understanding ion channel selectivity and gating and their role in cellular
      signalling.
AB  - Ion channels play an essential role in the communication between and within
      cells. Here some of the different ion channel proteins and the roles they perform
      are introduced, before a discussion of the mechanisms by which they discriminate
      between different ion types and open and close to allow the passage of ions at
      the appropriate times.

PMID- 17216035
TI  - Structure, function, and regulation of STAT proteins.
AB  - The Signal Transducer and Activator of Transcription (STAT) family of proteins
      was first discovered in the 1990's as key proteins in cytokine signaling. Since
      then, the field has greatly advanced in the past 15 years, providing significant
      insight into the structure, function, and regulation of STATs. STATs are latent
      cytoplasmic transcription factors consisting of seven mammalian members. They are
      Tyr phosphorylated upon activation, a post-translational modification critical
      for dimerization, nuclear import, DNA binding, and transcriptional activation. In
      recent years, unphosphorylated STATs have also been observed to dimerize and
      drive transcription, albeit by yet an obscure mechanism. In addition, the
      function of cytoplasmic STATs is beginning to emerge. Here, we describe the
      structure, function, and regulation of both unphosphorylated and phosphorylated
      STATs. STAT isoforms from alternative splicing or proteolytic processing, and
      post-translational modifications affecting STAT activities are also discussed.

PMID- 17216036
TI  - Direct detection of double-stranded DNA: Molecular methods and applications for
      DNA diagnostics.
AB  - Methodologies to detect DNA sequences with high sensitivity and specificity have
      tremendous potential as molecular diagnostic agents. Most current methods exploit
      the ability of single-stranded DNA (ssDNA) to base pair with high specificity to
      a complementary molecule. However, recent advances in robust techniques for
      recognition of DNA in the major and minor groove have made possible the direct
      detection of double-stranded DNA (dsDNA), without the need for denaturation,
      renaturation, or hybridization. This review will describe the progress in
      adapting polyamides, triplex DNA, and engineered zinc finger DNA-binding proteins
      as dsDNA diagnostic systems. In particular, the sequence-enabled reassembly
      (SEER) method, involving the use of custom zinc finger proteins, offers the
      potential for direct detection of dsDNA in cells, with implications for cell
      based diagnostics and therapeutics.

PMID- 17216037
TI  - A GFP-based assay for monitoring post-transcriptional regulation of ARE-mRNA
      turnover.
AB  - Interleukin-3 (IL3) mRNA is intrinsically labile due to the presence of a
      destabilizing AU-rich element (ARE) that targets the transcript for rapid
      degradation. We review our experience with a sensitive reporter system where
      changes in IL3 mRNA stability are translated into increased/decreased green
      fluorescent protein (GFP) signals. A GFP reporter gene was fused to the full
      length IL3 3'UTR containing the ARE motif that responds to regulatory signals
      that control transcript stability. The reporter system was tested against known
      IL3 mRNA stabilizing/destabilizing agents either through pharmacological
      treatment, siRNA knock-down of components of the decay machinery, mutation of the
      ARE motif, or in tumour lines harbouring stable IL3 mRNA. In all cases, the
      reporter transcript responds in an identical fashion to the endogenous IL3
      message thereby verifying the fidelity of the system. This reporter system allows
      screening and identification of novel ARE-mRNA stabilizing compounds, or the
      isolation of mutants defective in ARE-mRNA turnover. We also report preliminary
      attempts to modify the system for high-throughput screening of an extensive
      compound library. The simplicity and effectiveness of this screen makes it ideal
      for screening of modulators of clinically important ARE-bearing transcripts such
      as TNFalpha, VEGF, the interferons and other cytokines.

PMID- 17216038
TI  - Isolation and characterization of coactivator-binding peptoids from a
      combinatorial library.
AB  - Pharmacologic agents capable of activating the expression of specific genes would
      be valuable tools in biological research and could potentially be useful
      therapeutically. Efforts to develop a general solution to this problem have
      focused on the discovery of cell permeable mimics of native transcription factors
      comprised of linked DNA-binding and activation domain surrogates. Recently, we
      reported the isolation of a peptoid, called KBPo2, that binds a fragment of the
      mammalian coactivator CREB-binding protein (CBP). When delivered to a promoter
      bound DNA-binding domain, this peptoid acted as a potent activation domain mimic
      in human cells. In this paper, we provide full details of the screening
      experiments and also report further characterization of this molecule as well as
      the other peptoids that came out of the screen. Of the three peptoids identified
      as putative CBP ligands, only KBPo2 demonstrated the necessary combination of
      binding affinity, specificity and cell permeability necessary to function as a
      potent activation domain mimic in cells. KBPo2 binds to CBP in a region different
      than that recognized by the native activation peptide from the transcription
      factor CREB.

PMID- 17216040
TI  - Introduction to monitoring and manipulating signaling networks.

PMID- 17216039
TI  - Rational design of homogenous protein kinase assay platforms that allow both
      fluorometric and colorimetric signal readouts.
AB  - Protein kinases play important roles in signaling pathways that regulate many
      cellular biological processes, including apoptosis, cell growth, and
      differentiation in response to extracellular stimuli. Design of homogenous
      protein kinase assay platforms including design of potent protein kinase
      substrates is essential for exploration of the phosphoproteome. Here, we describe
      a unique chromism-based assay (CHROBA) technique for the direct measurement of
      protein kinase activities. The CHROBA is a novel chemosensor system that produces
      signals based on the photochromic and thermodynamic properties of a spiropyran
      derivative incorporated into peptide substrates. The CHROBA technique for
      detecting protein kinase activities involves the following five steps: (i)
      phosphorylation, (ii) photobleaching of the reaction mixture, (iii) addition of
      ionic polymer(s), (iv) incubation in the dark, and (v) signal readout. This
      simple 'end-point' assay method allows quantitative measurements of protein
      kinase A, Src protein tyrosine kinase, c-Abl protein tyrosine kinase, and protein
      kinase Calpha activities even with excess ATP. Our results showed that spiropyran
      containing peptide substrates with net charges between +2 and 0 are suitable for
      the present CHROBA method. This information should aid in the rational design of
      diverse protein kinase assay platforms. The present CHROBA technique can be
      adapted to a microplate format with both fluorometric and colorimetric readouts
      and would be useful for high-throughput drug discovery and analysis of the
      phosphoproteome.

PMID- 17216042
TI  - Towards high-throughput characterization of small molecule mechanisms of action.
AB  - Drug discovery is hampered by the lack of general strategies to characterize the
      mechanisms of action and intracellular targets of bioactive small molecules.
      Genomics and proteomics promise to aid in this process. Genome-wide approaches in
      yeast have proven useful to infer the targets and target pathways of small
      molecules. These approaches are being systematically transferred into mammalian
      cell culture systems in order to interrogate more complex pathways in a more
      relevant setting. Advances in proteomics and in vivo genetic screening in
      multicellular model organism systems are also becoming increasingly powerful and
      amenable to high-throughput. Current methodologies and technologies are
      discussed, including how these global approaches complement affinity-based target
      identification strategies.

PMID- 17216043
TI  - Alternative workflows for plant proteomic analysis.
AB  - High-throughput separations are intrinsic to the detection and analysis of
      peptides and proteins by mass spectrometry (MS). Together, efficient separation
      and MS can lead to the identification of thousands of proteins in a sample, cell
      or tissue and help build proteome maps that can be used to define a cell type or
      cellular state. Although 2D gels have been successfully used to separate proteins
      for subsequent MS analysis, alternative separation efficiencies and, consequently
      deeper results could be obtained with HPLC or other separation techniques that
      improve throughput. This highlight is aimed toward plant scientists who have
      special separation needs due to the nature of plant cells and who could benefit
      from knowing options and requirements for adopting alternative separation
      protocols. Through the various sample processing and protein separation
      strategies, plant biologists should be able to improve the quality of their
      proteomic reference maps and gain new information about the proteins that define
      plant cells.

PMID- 17216044
TI  - Genome-wide analysis of human HSF1 signaling reveals a transcriptional program
      linked to cellular adaptation and survival.
AB  - Although HSF1 plays an important role in the cellular response to proteotoxic
      stressors, little is known about the structure and function of the human HSF1
      signaling network under both stressed and unstressed conditions. In this study,
      we used a combination of chromatin immunoprecipitation microarray analysis and
      time course gene expression microarray analysis with and without siRNA-mediated
      inhibition of HSF1 to comprehensively identify genes regulated directly and
      indirectly by HSF1. The correlation between promoter binding and gene expression
      was not significant for all genes bound by HSF1, suggesting that HSF1 binding per
      se is not sufficient for expression. However, the correlation with promoter
      binding was significant for genes identified as HSF1-regulated following siRNA
      knockdown. Among promoters bound by HSF1 following heat shock, a gene ontology
      analysis showed significant enrichment only in categories related to protein
      folding. In contrast, analysis of the extended HSF1 signaling network following
      siRNA knockdown showed enrichment in a variety of categories related to protein
      folding, anti-apoptosis, RNA splicing, ubiquitinylation and others, highlighting
      a complex transcriptional program regulated directly and indirectly by HSF1.

PMID- 17216045
TI  - Insights into the behaviour of systems biology models from dynamic sensitivity
      and identifiability analysis: a case study of an NF-kappaB signalling pathway.
AB  - Mathematical modelling offers a variety of useful techniques to help in
      understanding the intrinsic behaviour of complex signal transduction networks.
      From the system engineering point of view, the dynamics of metabolic and signal
      transduction models can always be described by nonlinear ordinary differential
      equations (ODEs) following mass balance principles. Based on the state-space
      formulation, many methods from the area of automatic control can conveniently be
      applied to the modelling, analysis and design of cell networks. In the present
      study, dynamic sensitivity analysis is performed on a model of the IkappaB-NF
      kappaB signal pathway system. Univariate analysis of the Euclidean-form overall
      sensitivities shows that only 8 out of the 64 parameters in the model have major
      influence on the nuclear NF-kappaB oscillations. The sensitivity matrix is then
      used to address correlation analysis, identifiability assessment and measurement
      set selection within the framework of least squares estimation and multivariate
      analysis. It is shown that certain pairs of parameters are exactly or highly
      correlated to each other in terms of their effects on the measured variables. The
      experimental design strategy provides guidance on which proteins should best be
      considered for measurement such that the unknown parameters can be estimated with
      the best statistical precision. The whole analysis scheme we describe provides
      efficient parameter estimation techniques for complex cell networks.

PMID- 17216046
TI  - Biological network design strategies: discovery through dynamic optimization.
AB  - An important challenge in systems biology is the inherent complexity of
      biological network models, which complicates the task of relating network
      structure to function and of understanding the conceptual design principles by
      which a given network operates. Here we investigate an approach to analyze the
      relationship between a network structure and its function using the framework of
      optimization. A common feature found in a variety of biochemical networks
      involves the opposition of a pair of enzymatic chemical modification reactions
      such as phosphorylation-dephosphorylation or methylation-demethylation. The
      modification pair frequently adjusts biochemical properties of its target, such
      as activating and deactivating function. We applied optimization methodology to
      study a reversible modification network unit commonly found in signal
      transduction systems, and we explored the use of this methodology to discover
      design principles. The results demonstrate that different sets of rate constants
      used to parameterize the same network topology represent different compromises
      made in the resulting network operating characteristics. Moreover, the same
      topology can be used to encode different strategies for achieving performance
      goals. The ability to adopt multiple strategies may lead to significantly
      improved performance across a range of conditions through rate modulation or
      evolutionary processes. The optimization framework explored here is a practical
      approach to support the discovery of design principles in biological networks.

PMID- 17216047
TI  - Molecular modelling.

PMID- 17216050
TI  - The future of proteomic analysis in biological systems and molecular medicine.
AB  - Proteomics is the study of proteins and their interactions within complex
      biological systems. While this field is often associated with mass spectrometry,
      it is more useful to consider proteomics in the context of an objective: to
      identify and understand the molecular basis of health and disease at the protein
      level in vivo. Achieving this objective will require (1) technological
      developments to resolve current instrument limitations and (2) multidisciplinary
      integration of biological and protein analysis technologies to answer important
      questions in both the biological sciences and molecular medicine.

PMID- 17216051
TI  - Controlling influenza virus replication by inhibiting its proton channel.
AB  - Influenza A and viruses encode minimalistic proton-selective ion channels known
      as A/M2 and BM2, respectively. The A/M2 channel is the target of the antiviral
      drug, amantadine. The structural and mechanistic aspects of proton conductance of
      the viral ion channels are described and the review makes a case for the
      development of more effective antivirals.

PMID- 17216052
TI  - Control of macromolecular structure and function using covalently attached double
      stranded DNA constraints.
AB  - The biophysical properties of DNA suggest its use for applications beyond serving
      as the genetic material. Several recent reports describe the use of covalently
      attached double-stranded DNA for controlling the structures of other
      macromolecules such as protein and RNA. These exploitations of DNA rigidity are
      conceptually distinct from many other studies in the area of "DNA
      nanotechnology". Double-stranded DNA constraints provide a means of introducing
      selective tension onto other molecules. This should facilitate fundamental
      investigations of macromolecular folding landscapes and tertiary interactions, as
      well as allow study of the mechanotransduction of biochemical signals. Use of a
      DNA constraint as the key element of a sensor has already been demonstrated, and
      such applications will be enhanced by improvements in the signal readout methods.
      If practical challenges such as delivery and stability can be addressed, these
      new efforts may also enable development of selective sensors for in vivo
      applications.

PMID- 17216053
TI  - Design of radiolabelled ligands for the imaging and treatment of cancer.
AB  - The specialised medical field of Nuclear Medicine is concerned with the use of
      unsealed sources of radioactivity either to diagnose or treat a range of
      diseases. In this regard it can be distinguished from the field of Radiotherapy
      which uses sealed radioactive sources for treatment. The range of diseases in
      which Nuclear Medicine plays a role is wide and includes, among others, the
      fields of microbiology, endocrinology, neurology, oncology and cardiovascular
      medicine. However, cancer probably represents the most important and growing area
      of application for this modality. Nuclear Medicine employs radiopharmaceuticals.
      These are radiolabelled ligands that have the ability to interact with molecular
      targets that are relevant in the aetiology or treatment of cancer and in many
      respects Nuclear Medicine can be considered the archetype for the application of
      'Molecular Medicine'. An example of a Nuclear Medicine Positron Emission
      Tomography (PET) scan is shown in Fig. 2. There is great interest in developing
      new radioligands that allow us to image the expression of the ever increasing
      range of biological pathways being discovered in the post-genomic area. Designing
      effective radiopharmaceuticals, however, requires an understanding of a number of
      radiopharmaceutical sciences including aspects of chemistry, physics, cell and
      molecular biology, and physiology.

PMID- 17216054
TI  - A novel antibody microarray format using non-covalent antibody immobilization
      with chemiluminescent detection.
AB  - To date, protein and antibody microarrays have been used in reverse-phase and
      sandwich-based methods in order to detect known proteins such as biomarkers in
      samples. Our group developed "libraries" of antibodies against unknown proteins,
      referred to as mKIAA proteins, and we attempted to discover candidate novel
      biomarkers by protein expression profiling.To profile mKIAA protein expression
      using these antibodies, we established an antibody microarray system using
      chemiluminescent detection. A number of techniques for protein-antibody
      microarrays have been reported; however, no entirely suitable protocol for crude
      protein samples has been established. To address this issue, we immobilized
      purified antibodies on hydrophilic surface polymer slides (Maxisorp, Nunc).
      Although our system is based on the direct labeling of crude protein samples, we
      achieved sufficient sensitivity (detection limit: 50 pg mL(-1)) and low
      backgrounds. This sensitivity is on a level with the sandwich immunoassay-based
      antibody array system. Using our protocol, we developed an antibody microarray
      spotted with 960 anti-mKIAA antibodies (total: 3888 spots for quadruplicate
      assessments), and we carried out protein expression profiling of mKIAA proteins.
      In this study, we generated an expression profile of 960 mKIAA proteins and
      compared the present results with those obtained via cDNA microarray.

PMID- 17216055
TI  - MALDI-TOF mass spectral analysis of siRNA degradation in serum confirms an RNAse
      A-like activity.
AB  - Synthetic siRNA duplexes are used widely as reagents for silencing of mRNA
      targets in cells and are being developed for in vivo use. Serum stability is a
      major concern if siRNA is to be used for therapeutic delivery within blood
      circulation. We have developed the use of MALDI-TOF mass spectrometry as a rapid
      and convenient analytical tool to identify the most vulnerable sites within siRNA
      to serum degradation. Using this approach, we found that one siRNA duplex (Dh3)
      with UpA sequences close to one end was particularly vulnerable to rapid
      cleavage. This produced a fragment of mass consistent with the presence of a
      2',3'-cyclic phosphate that was slowly hydrolysed to a 2'-(3'-)phosphate on
      extended incubation. Substitution of these sites with 2'-O-methyl U residues
      prevented cleavage and confirmed that the major pathway for initial degradation
      is via cleavage by an RNAse A-like activity. Mass spectral analysis was used to
      follow the serum degradation of siRNA over more prolonged periods to show the
      accumulation of many fragments, almost all showing cleavage following pyrimidine
      nucleoside residues. Overall, the MALDI-TOF mass spectral analysis technique
      should prove useful for preliminary screening of the serum stability of siRNA
      duplexes and for identification of the most vulnerable cleavage sites.

PMID- 17216057
TI  - The tallysomycin biosynthetic gene cluster from Streptoalloteichus hindustanus
      E465-94 ATCC 31158 unveiling new insights into the biosynthesis of the bleomycin
      family of antitumor antibiotics.
AB  - The tallysomycins (TLMs) belong to the bleomycin (BLM) family of antitumor
      antibiotics. The BLM biosynthetic gene cluster has been cloned and characterized
      previously from Streptomyces verticillus ATCC 15003, but engineering BLM
      biosynthesis for novel analogs has been hampered by the lack of a genetic system
      for S. verticillus. We now report the cloning and sequencing of the TLM
      biosynthetic gene cluster from Streptoalloteichus hindustanus E465-94 ATCC 31158
      and the development of a genetic system for S. hindustanus, demonstrating the
      feasibility to manipulate TLM biosynthesis in S. hindustanus by gene inactivation
      and mutant complementation. Sequence analysis of the cloned 80.2 kb region
      revealed 40 open reading frames (ORFs), 30 of which were assigned to the TLM
      biosynthetic gene cluster. The TLM gene cluster consists of nonribosomal peptide
      synthetase (NRPS) genes encoding nine NRPS modules, a polyketide synthase (PKS)
      gene encoding one PKS module, genes encoding seven enzymes for deoxysugar
      biosynthesis and attachment, as well as genes encoding other biosynthesis,
      resistance, and regulatory proteins. The involvement of the cloned gene cluster
      in TLM biosynthesis was confirmed by inactivating the tlmE glycosyltransferase
      gene to generate a TLM non-producing mutant and by restoring TLM production to
      the DeltatlmE::ermE mutant strain upon expressing a functional copy of tlmE. The
      TLM gene cluster is highly homologous to the BLM cluster, with 25 of the 30 ORFs
      identified within the two clusters exhibiting striking similarities. The
      structural similarities and differences between TLM and BLM were reflected
      remarkably well by the genes and their organization in their respective
      biosynthetic gene clusters.

PMID- 17216056
TI  - Chemical genetics suggests a critical role for lysyl oxidase in zebrafish
      notochord morphogenesis.
AB  - As a result of a chemical genetic screen for modulators of metalloprotease
      activity, we report that 2-mercaptopyridine-N-oxide induces a conspicuous
      undulating notochord defect in zebrafish embryos, a phenocopy of the leviathan
      mutant. The location of the chemically-induced wavy notochord correlated with the
      timing of application, thus defining a narrow chemical sensitivity window during
      segmentation stages. Microscopic observations revealed that notochord undulations
      appeared during the phase of notochord cell vacuolation and notochord elongation.
      Notochord cells become swollen as well as disorganized, while electron microscopy
      revealed disrupted organization of collagen fibrils in the surrounding sheath. We
      demonstrate by assay in zebrafish extracts that 2-mercaptopyridine-N-oxide
      inhibits lysyl oxidase. Thus, we provide insight into notochord morphogenesis and
      reveal novel compounds for lysyl oxidase inhibition. Taken together, these data
      underline the utility of small molecules for elucidating the dynamic mechanisms
      of early morphogenesis and provide a potential explanation for the recently
      established role of copper in zebrafish notochord formation.

PMID- 17216058
TI  - Fiddling the string of carbon nanotubes with amphiphiles.
AB  - The field of carbon nanotube-amphiphile self assembly has been reviewed to
      address the ongoing debate regarding their binding. Based on our
      spectrophotometry and transmission electron microscopy studies, this report shows
      the binding of lysophospholipids onto carbon nanotubes is dependent on the charge
      and geometry of the lipids and the pH of the solvent, and independent of solvent
      temperature. From molecular dynamics simulations, the binding of
      lysophospholipids onto carbon nanotubes does not fully obey any of the models
      proposed in the literature. We also studied carbon nanotube diffusion using
      single-molecule fluorescence microscopy, and carbon nanotube-lipid binding and
      dissociation using the technique of fluorescence resonance energy transfer. The
      use of carbon nanotube-lipid assembly for enabling nanotoxicological studies is
      demonstrated by the uptake of the assembly in the living organism Daphnia magna.

PMID- 17216059
TI  - Can the DFT-D method describe the full range of noncovalent interactions found in
      large biomolecules?
AB  - The DFT-D method is shown to yield interaction energies between biologically
      important groups to an accuracy comparable to that obtained using state-of-the
      art ab initio methods.

PMID- 17216060
TI  - Mechanistic aspects of proton chain transfer in the green fluorescent protein.
      Part II. A comparison of minimal quantum chemical models.
AB  - In this paper we report the results of extensive quantum chemical reaction
      pathway calculations for the electronic ground state of several different cluster
      models that mimic the proton chain transfer path within the green fluorescent
      protein (GFP). Our principal objective is to establish the robustness with
      respect to variations in the model of our recent mechanistic inferences for the
      ground state proton chain transfer [S. Wang and S. C. Smith, J. Phys. Chem. B,
      2006, 110, 5084]. Additionally, comparison of our ground state results with the
      excited state proton transfer (ESPT) study by Vendrell et al. [O. Vendrell, R.
      Gelabert, M. Moreno and J. M. Lluch, J. Am. Chem. Soc., 2006, 128, 3564] leads to
      the conclusion that the mechanism of proton chain transfer may be expected to be
      analogous in ground and excited states, principally because in both cases the
      loss of the chromophore's phenolic proton contributes strongly to the reaction
      coordinate only late in the reaction path.

PMID- 17216061
TI  - Approaching actinide(+III) hydration from first principles.
AB  - A systematic computational approach to An(III) hydration on a density-functional
      level of theory, using quasi-relativistic 5f-in-core pseudopotentials and valence
      only basis sets for the An(III) subsystems, is presented. Molecular structures,
      binding energies, hydration energies, and Gibbs free energies of hydration have
      been calculated for [An(III)(OH(2))(h)](3+) (h = 7, 8, 9) and [An(III)(OH(2))(h
      1) * OH(2)](3+) (h = 8, 9), using large (7s6p5d2f1g)/[6s5p4d2f1g] An(III) and cc
      pVQZ O and H basis sets within the COSMO implicit solvation model. An(III)
      preferred primary hydration numbers are found to be 8 for all An(III) at the
      gradient-corrected density-functional level of theory. Second-order Moller
      Plesset perturbation theory predicts preferred primary hydration numbers of 9 and
      8 for Ac(III)-Md(III) and No(III)-Lr(III), respectively.

PMID- 17216062
TI  - Ab initio study on the decomposition of first excited state HOOO radicals.
AB  - The HOOO radical plays a crucial role in atmospheric processes involving the OH
      radical and O(2) molecule. We present an ab initio molecular orbital theory study
      on the decomposition reaction of the first excited state HOOO((2)A') with respect
      to OH and O(2). The geometries and harmonic vibrational frequencies of all
      stationary points are calculated at the CASSCF and MRCI levels of theory in
      conjunction with the 6-31+G(d,p) basis set. The potential energy profile of the
      decomposition reaction is studied at the CASSCF/6-31+G(d,p) level of theory, in
      which the complete valence orbitals and electrons are included in the active
      space. The energies of the potential energy profile are further refined at the
      CASPT2 and MRCI levels of the theory. Additionally, we have determined the
      interesting reaction process: the HOOO((2)A') radical with C(s) symmetry does not
      dissociate to OH((2)Pi) and O(2)((3)Sigma(-)(g)) directly as this is forbidden by
      orbital symmetry, but dissociates to OH((2)Pi) and O(2)((3)Sigma(-)(g)) via the
      change in symmetry from C(s) to C(infinity v) symmetry with a low barrier.

PMID- 17216063
TI  - p-Benzoquinone in aqueous solution: Stark shifts in spectra, asymmetry in solvent
      structure.
AB  - Results from a simulation of p-benzoquinone (PBQ) in water is presented. An
      explicit solvent representation is used together with a multiconfigurational ab
      initio quantum chemical method. The electronic n --> pi* transitions are studied
      in aqueous solution and the two such transitions are both blue-shifted but to
      different degree. Both non-equilibrium and many-body effects are found to have
      decisive influence on the solvation: despite stronger hydrogen bonding between
      solute and solvent in an excited state than in the ground state, there is a blue
      shift, and the solvent structure around the non-polar PBQ is asymmetric, which is
      argued to come from special many-body effects. The unusual result of strengthened
      hydrogen bonds in the excited state that follows from an excitation of a non
      bonding electron on a proton acceptor, is explained by the near-linear Stark
      shift that is present in the transition.

PMID- 17216064
TI  - Experimental and quantum-chemical determination of the (2)H quadrupole coupling
      tensor in deuterated benzenes.
AB  - Deuterium Quadrupole Coupling Constant (DQCC) in benzene was determined both
      experimentally by Nuclear Magnetic Resonance spectroscopy in Liquid Crystalline
      solutions (LC NMR) and theoretically by ab initio electronic structure
      calculations. DQCCs were measured for benzene-d(1) and 1,3,5-benzene-d(3) using
      several different liquid crystalline solvents and taking vibrational and
      deformational corrections into account in the analysis of experimental dipolar
      couplings, used to determine the orientational order parameter of the dissolved
      benzene. The experimental DQCC results for the isotopomers benzene-d(1) and 1,3,5
      benzene-d(3) are found to be 187.7 kHz and 187.3 kHz, respectively, which are
      essentially equal within the experimental accuracy (+/-0.4 kHz). Theoretical
      results were obtained at different C-D bond lengths, and by applying corrections
      for electron correlation and rovibrational motion on top of large-basis-set
      Hartree-Fock results. The computations give a consistent DQCC of ca. 189 kHz for
      three different isotopomers; benzene-d(1), 1,3,5-benzene-d(3), and benzene-d(6),
      revealing that isotope effects are not detectable within the present experimental
      accuracy. Calculations carried out using a continuum solvation model to account
      for intermolecular interaction effects result in very small changes as compared
      to the data obtained in vacuo. The comparison of theoretical and experimental
      results points out the selection of the underlying molecular geometry as the most
      likely source of the remaining discrepancy of less than 2 kHz. Such an agreement
      between the calculated and the experimental DQCC results can only be achieved if
      rovibrational effects are considered on one hand in the experimental direct
      dipolar coupling data, and on the other hand in the theoretical property
      calculation, as is done presently.

PMID- 17216065
TI  - High temperature optical spectroscopy of cubic holmium doped zirconia,
      Zr(0.78)Y(0.21)Ho(0.01)O(1.90).
AB  - The electronic absorption spectra of a Zr(0.78)Y(0.21)Ho(0.01)O(1.90) single
      crystal have been measured in in situ conditions between room temperature and
      1289 K. The evolution of the spectra with rising temperatures is characterised by
      an overall increase in intensity. Notably the intensities of the (5)I(8) -->
      (5)F(2), (5)I(8) --> (5)S(2) and (5)I(8) --> (5)G(6) transitions increase by
      factors of two to three. The evaluation of the spectral parameters favours the
      conclusion that the intensity increases are due to vibronic coupling associated
      with effective frequencies ranging between 1 x 10(13) and 5 x 10(13) s(-1) (330
      cm(-1) and 1670 cm(-1)). The changes in the optical spectra are reversible and
      are not connected with structural changes in the material.

PMID- 17216066
TI  - A computational characterization of the hydrogen-bonding and stacking
      interactions of hypoxanthine.
AB  - The hydrogen-bonding and stacking interactions of hypoxanthine, a potential
      universal nucleobase, were calculated using a variety of methodologies (CCSD(T),
      MP2, B3LYP, PWB6K, AMBER). All methods predict that the hydrogen-bonding
      interaction in the hypoxanthine-cytosine pair is approximately 25 kJ mol(-1)
      stronger than that in the other dimers. Although the calculations support
      suggestions from experiments that hypoxanthine preferentially binds with
      cytosine, the trend in the calculated hydrogen-bond strengths for the remaining
      natural nucleobases do not show a strong correlation with the experimentally
      predicted binding preferences. However, our calculations suggest that the
      stacking interactions of hypoxanthine are similar in magnitude to the hydrogen
      bonding interactions at all levels of theory (with the exception of B3LYP, which
      incorrectly predicts stacked dimers to be unstable). Therefore, stacking
      interactions should also be considered when analyzing the stability of DNA
      helices containing hypoxanthine and the use of larger models that account for
      both hydrogen-bonding and stacking within DNA duplexes will likely result in
      better agreement with experimental observations. For the majority of the dimers,
      PWB6K and AMBER provide reasonable binding strengths at reduced computational
      costs, and therefore will be useful techniques for considering larger models.

PMID- 17216067
TI  - Direct attachment of well-aligned single-walled carbon nanotube architectures to
      silicon (100) surfaces: a simple approach for device assembly.
AB  - A new approach for the attachment of vertically-aligned shortened carbon nanotube
      architectures to a silicon (100) substrate by chemical anchoring directly to the
      surface has been demonstrated for the first time. The ordered assembly of single
      walled carbon nanotubes (SWCNTs) was accomplished by hydroxylating the silicon
      surface followed by a condensation reaction with carboxylic acid functionalised
      SWCNTs. This new nanostructure has been characterised by X-ray photoelectron,
      Raman and Fourier transform infrared (FTIR) spectroscopy as well as scanning
      electron and atomic force microscopy. The assembly behaviour of SWCNTs onto the
      silicon surface shows a fast initial step producing isolated functionalised
      carbon nanotubes or nanotube bundles anchored to the silicon surface followed by
      a slower step where the adsorbed nanotubes grow into larger aggregates via van
      der Waals interactions between adsorbed and solvated nanotubes. The
      electrochemical and optical properties of the SWCNTs directly attached to silicon
      have also been investigated. These new nanostructures are excellent
      electrochemical electrodes. They also fluoresce in the wavelength range 650-800
      nm. The successful attachment of the SWCNTs directly to silicon provides a
      simple, new avenue for fabrication and development of silicon-based
      nanoelectronic, nano-optoelectronic and sensing devices. Compared to existing
      techniques, this new approach has several advantages including low operating
      temperature, low cost and the possibility of further modification.

PMID- 17216068
TI  - Interplay of water, extra-framework cations and framework atoms in the structure
      of low-silica zeolites: the case of the natural zeolite Goosecreekite as studied
      by computer simulation.
AB  - Computational methods are described that model accurately the structure of
      hydrated Ca-bearing zeolites. Using Goosecreekite as a model system we probe the
      influence of framework ordering, cation siting and hydration of pores on the
      structure and its stability. We develop a methodology which allows the location
      of Al within the framework to be determined together with the position of extra
      framework cations, in a stepwise fashion, progressing from an anhydrous model,
      via a dielectric continuum model, to finally, a fully atomistic model of the
      water in the intrazeolite pore space. Our methods reveal the complex interplay of
      short- and long-range interactions on the optimal structure of such materials.

PMID- 17216071
TI  - Tear crystallization test: two centuries of history.

PMID- 17216069
TI  - Comparison of the reactivity of different Pd-O species in CO oxidation.
AB  - The reactivity of several Pd-O species toward CO oxidation was compared
      experimentally, making use of chemically, structurally and morphologically
      different model systems such as single-crystalline Pd(111) covered by adsorbed
      oxygen or a Pd(5)O(4) surface oxide layer, an oriented Pd(111) thin film on NiAl
      oxidized toward PdO(x) suboxide and silica-supported uniform Pd nanoparticles
      oxidized to PdO. The oxygen reactivity decreased with increasing oxidation state:
      O(ad) on metallic Pd(111) exhibited the highest reactivity and could be reduced
      within a few minutes already at 223 K, using low CO beam fluxes around 0.02 ML s(
      1). The Pd(5)O(4) surface oxide on Pd(111) could be reacted by CO at a comparable
      rate above 330 K using the same low CO beam flux. The more deeply oxidized
      Pd(111) thin film supported on NiAl was already much less reactive, and reduction
      in 10(-6) mbar CO at T > 500 K led only to partial reduction toward PdO(x)
      suboxide, and the metallic state of Pd could not be re-established under these
      conditions. The fully oxidized PdO nanoparticles required even rougher reaction
      conditions such as 10 mbar CO for 15 min at 523 K in order to re-establish the
      metallic state. As a general explanation for the observed activity trends we
      propose kinetic long-range transport limitations for the formation of an
      extended, crystalline metal phase. These mass-transport limitations are not
      involved in the reduction of O(ad), and less demanding in case of the 2-D
      Pd(5)O(4) surface oxide conversion back to metallic Pd(111). They presumably
      become rate-limiting in the complex separation process from an extended 3-D bulk
      oxide state toward a well ordered 3-D metallic phase.

PMID- 17216072
TI  - Four-dimensional multiphoton confocal microscopy: the new frontier in cellular
      imaging.
AB  - This paper reviews new developments in microscopy that combine gene transfer
      technology, multiphoton confocal fluorescence microscopy, live cell imaging and
      digital imaging techniques that provide unique insights into the complex
      physiological processes involved in tissue function at the cellular and
      subcellular level. The evolution of this novel, new technology is discussed with
      particular attention to earlier achievements in noninvasive ocular surface
      imaging. The practical basis of confocal microscopy, multiphoton confocal
      fluorescence microscopy, and the vital fluorescent labeling of cells in living
      tissues are also discussed. Additionally, one application using retroviral gene
      transfer to express enhanced green fluorescent protein in living wound healing
      fibroblasts is presented as an example of how living biology can be studied in
      situ in four dimensions (x, y, z, time).

PMID- 17216073
TI  - Concept and clinical application of cultivated epithelial transplantation for
      ocular surface disorders.
AB  - Corneal epithelial replacement using a tissue engineering technique holds much
      promise for ocular surface reconstruction in cases of corneal epithelial stem
      cell deficiency. However, even though an autologous cultivated corneal epithelial
      stem cell sheet is the safest and most reliable form of sheet, bilaterally
      affected ocular surface disorders cannot be treated by this method. To treat
      bilateral cases, we must choose either an allogeneic cultivated corneal
      epithelial sheet or an autologous cultivated oral mucosal epithelial sheet. In
      the case of the former, immunological reaction is a threat. Thus, understanding
      of the immunological background of ocular surface reconstruction using allogeneic
      tissues is essential. In the case of the latter, the transplanted sheet is not
      exactly the same as corneal epithelium, and understanding ocular surface
      epithelial biology is important. In this review, we summarize and explain the
      concept and clinical application of cultivated mucosal epithelial transplantation
      for ocular surface disorders.

PMID- 17216074
TI  - The effects of LASIK on the ocular surface.
AB  - Laser in situ keratomileusis (LASIK) can affect corneal sensation, aqueous tear
      production, wound healing, and the incidence of corneal erosions. Virtually all
      patients experience dry eye at least transiently after LASIK. Because intact
      corneal sensation drives tear production, denervation associated with the LASIK
      procedure is the most significant cause of post-LASIK dry eye. To prevent
      symptomatic postoperative dry eye, it is crucial to identify and treat pre
      existing dry eye before surgery. This review addresses the pathophysiology and
      management of dry eye, as well as the relationship between LASIK and corneal
      erosions, and suggests intra- and post-operative management techniques to
      minimize complications and maximize the stability of the ocular surface.
      Contraindications to LASIK and alternative refractive surgical procedures are
      discussed.

PMID- 17216075
TI  - The CONSORT statement for publication of controlled clinical trials.

PMID- 17216076
TI  - Kenneth A. Polse, OD, MS.

PMID- 17216077
TI  - The range of ocular surface research at the University of Texas Southwestern
      Medical Center, Dallas.

PMID- 17216079
TI  - Aniridia and the ocular surface.

PMID- 17216080
TI  - New insights into the diagnosis and treatment of dry eye.
AB  - Over the past decade, numerous advances have been made in relation to dry eye
      diagnostic markers, technologies, and treatment options. The mainstay of
      treatment of dry eye is the use of artificial tear solutions and punctum plugs. A
      goal is the development of agents that provide symptomatic treatment and, at the
      same time, improve ocular surface keratinization. It is the authors' opinion that
      the functional visual acuity tester and the new tear stability analysis system
      will be widely used to improve diagnosis and evaluate treatment outcomes in KCS.
      Advances in treatment will utilize anti-inflammatory agents, immune suppressants
      such as Cyclosporin A and FK-506, growth hormones, androgens, topical mucins and
      ocular surface stimulating drugs, like INS365. Although aqueous-deficient dry eye
      is most commonly not associated with Sjogren syndrome (SS), aqueous-deficient dry
      eye is often most severe in patients with SS; thus, this article focuses mainly
      on SS-associated dry eye.

PMID- 17216081
TI  - Dysfunctional neural regulation of lacrimal gland secretion and its role in the
      pathogenesis of dry eye syndromes.
AB  - Tears are a complex fluid consisting of three layers, each of which is secreted
      by a different set of tissues or glands. The aqueous portion of the tear film is
      produced predominantly by the lacrimal gland. Dry eye syndromes are diseases in
      which the amount and composition of tears are altered, which can lead to ocular
      surface damage. There are many causes for dry eye syndromes. One such cause is
      the alteration in the functions of nerves innervating the lacrimal gland and the
      ocular surface. The autoimmune disease Sjogren syndrome can deleteriously affect
      the innervation of the lacrimal gland. Damage to the sensory nerves in the ocular
      surface, specifically the cornea, as a result of refractive surgery and normal
      aging, prevents the normal reflex arc to the lacrimal gland. Both defects can
      result in decreased tear secretion and dry eye syndromes. This review will
      discuss the current information regarding neurally-stimulated protein, water, and
      electrolyte secretion from the lacrimal gland and delineate how nerve dysfunction
      resulting from a variety of causes decreases secretion from this gland.

PMID- 17216082
TI  - Tearful relationships? Sex, hormones, the lacrimal gland, and aqueous-deficient
      dry eye.
AB  - Sex and the endocrine system exert a significant influence on the physiology and
      pathophysiology of the lacrimal gland. The purpose of this article is to briefly
      review the nature and magnitude of these interactions between sex, hormones and
      lacrimal tissue, and to address how they may relate to the pathogenesis of
      aqueous-deficient dry eye. Towards this end, this article has a 3-fold approach:
      first, to summarize the influence of androgens, estrogens, glucocorticoids,
      mineralocorticoids, retinoic acid, prolactin, alpha-melanocyte stimulating
      hormone, adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating
      hormone, growth hormone, thyroid-stimulating hormone, arginine vasopressin,
      oxytocin, thyroxine, parathyroid hormone, insulin, glucagon, melatonin, human
      chorionic gonadotropin and cholecystokinin on the structure and function of the
      lacrimal gland; second, to discuss the mechanism of action of each hormone on
      lacrimal tissue; and third, to discuss the clinical relevance of the endocrine
      lacrimal gland interrelationship, with a particular focus on each hormone's role
      (i.e. if relevant) in the development of aqueous-tear deficiency.

PMID- 17216083
TI  - Inflammation in dry eye.
AB  - Dry eye is a condition of altered tear composition that results from a diseased
      or dysfunctional lacrimal functional unit. Evidence suggests that inflammation
      causes structural alterations and/or functional paralysis of the tear-secreting
      glands. Changes in tear composition resulting from lacrimal dysfunction,
      increased evaporation and/or poor clearance have pro-inflammatory effects on the
      ocular surface. This inflammation is responsible in part for the irritation
      symptoms, ocular surface epithelial disease, and altered corneal epithelial
      barrier function in dry eye. Anti-inflammatory therapies for dry eye target one
      or more of the inflammatory mediators/pathways that have been identified in dry
      eye.

PMID- 17216084
TI  - Character of ocular surface mucins and their alteration in dry eye disease.
AB  - At the ocular surface, three types of mucins are present. The large gel-forming
      mucin MUC5AC is expressed by conjunctival goblet cells. Some cells of the
      lacrimal gland acini express the small soluble mucin MUC7. The corneal and
      conjunctival epithelia express the membrane-associated mucins MUCs 1, 4, and 16.
      With the characterization of the mucin gene repertoire of the ocular surface
      epithelia, studies of the function of specific mucins, their gene regulation, and
      their alteration in ocular surface disease have begun. Current information
      suggests that all the mucins are hydrophilic and play a role in maintenance of
      water on the surface of the eye. The large secreted mucins represent the
      "janitorial service" that moves over the surface of the eye to wrap up and remove
      debris. The membrane-associated mucins form the glycocalyx, which provides a
      continuous barrier across the surface of the eye that prevents pathogen
      penetrance and has signaling capabilities that influence epithelial activity.
      Factors regulating mucin gene expression include retinoic acid, serum, and
      dexamethasone. Alteration in both secreted and membrane-associated mucins occur
      in drying ocular surface diseases. In Sjogren syndrome, MUC5AC expression is
      reduced, and in non-Sjogren dry eye, glycosylation of MUC16 appears to be
      altered. The pattern of expression of enzymes that glycosylate mucins is altered
      in ocular cicatricial pemphigoid. Therapies being evaluated for dry eye,
      including cyclosporine A, P2Y2 agonists, gefarnate, 15-(S)-HETE, and
      corticosteroids, may be efficacious due to their effect on mucin gene expression
      and secretion.

PMID- 17216086
TI  - Development of topical agents.

PMID- 17216085
TI  - The contribution of meibomian disease to dry eye.
AB  - The tear film lipid layer is the major barrier to evaporation from the ocular
      surface. A decrease in its thickness or functional integrity may cause
      evaporative dry eye (EDE). Obstructive meibomian gland dysfunction (MGD) is the
      most common cause of EDE and occurs as a primary disorder or secondary to acne
      rosacea, seborrheic or atopic dermatitis, and with cicatrizing conjunctival
      disorders, such as trachoma, erythema multiforme, and cicatricial pemphigoid. MGD
      may be an incidental finding in asymptomatic eyes, or it may be responsible for
      irritative lid symptoms in the absence of dry eye. MGD-dependent EDE is diagnosed
      on the basis of a defined degree of MGD in a symptomatic patient showing typical
      ocular surface damage in the absence of an aqueous tear deficiency. When MGD
      occurs in a background of aqueous tear deficiency (ATD), then an additional
      evaporative component may assumed, depending on the extent of meibomian
      obstruction. However, definitive criteria are not yet established. The clinical
      severity of dry eye is greatest when ATD and EDE occur together, particularly in
      Sjogren syndrome. A hypothesis is proposed to explain the steps leading to
      primary, simple MGD and subsequent EDE.

PMID- 17216088
TI  - Ocular surface reflex in pseudocelli.
AB  - Light, when striking the ocular surface of terrestrial animals, is partially
      reflected by the lacrimal film, which can be seen as a bright spot on the cornea.
      This reflection, termed "the corneal reflex," should actually be called the
      "lacrimal film reflex," as it is reflected mainly by the lacrimal film. An
      isolated corneal reflex exists only in aquatic animals, which have no lacrimal
      film, and in abnormal conditions in terrestrial animals, e.g., when their corneas
      become dry. Some animals are able to mimic and reproduce the external appearance
      of the eyes of other species for defensive display purposes. In these eye-spots
      or pseudocelli, the ocular surface reflex is present as an important physiognomic
      feature in terrestrial animals. However, we have observed that it is absent in
      aquatic animals. We hypothesize that the corneal reflex of aquatic animals is
      very weak and inconspicuous due to the small difference of refractive index
      between water and cornea, and for this reason is not a physiognomic
      characteristic of their eyes. Thus, pseudocelli present on sub-aquatic animals do
      not display an ocular surface reflex.

PMID- 17216089
TI  - How does amniotic membrane work?
AB  - Transplantation of amniotic membrane as a temporary or permanent graft promotes
      epithelial wound healing and exerts potent anti-inflammatory and anti-scarring
      effects on the ocular surface. These actions depend on the killing of allogeneic
      amniotic cells and preservation of the cytokine-containing matrix during the
      preparation of the amniotic membrane. This review describes how these actions
      inherently operate in utero and how amniotic membrane transplantation aims to
      recreate such a fetal environment to exert these actions by insulating the
      surgical site from the host environment. These actions also render the amniotic
      membrane a unique niche capable of expanding both epithelial and mesenchymal
      progenitor cells ex vivo, while maintaining their normal cell phenotypes. As a
      result, the amniotic membrane becomes an ideal substrate for engineering
      different types of ocular surface tissues for transplantation. Further studies
      investigating the exact molecular mechanism by which the amniotic membrane works
      will undoubtedly unravel additional applications in reconstruction and
      engineering of both ocular and nonocular tissues in the burgeoning field of
      regenerative medicine.

PMID- 17216090
TI  - Ocular surface influences on corneal topography.
AB  - The shape of a cornea, as measured by corneal topography, can be influenced by a
      variety of factors. Direct and obvious influences on corneal shape include
      corneal pathology, corneal surgery, and contact lenses. With the modern and
      widespread use of computerized videokeratoscopy, subtle topographic changes from
      other external and systemic influences can now be detailed. The purpose of this
      review is to examine ocular surface influences and indirect surgical,
      pathological, and pharmacological factors that affect the corneal shape and
      acquired topographic maps. The clinical consequences of altered corneal
      topography will be highlighted throughout.

PMID- 17216092
TI  - Amniotic membrane transplantation in the management of severe ocular surface
      disease: indications and outcomes.
AB  - Since 1995, with the availability of cryopreserved amniotic membrane (AM), the
      use of AM as a patch or graft for ocular surface reconstruction has become
      recognized as an important alternative for treatment of persistent epithelial
      defects and sterile ulceration that are refractory to conventional therapy. A
      major problem with evaluating the efficacy of AM transplantation is the lack of
      controlled clinical studies. Moreover, for some diseases there is no accepted
      "standard" therapy, and the incidence of the disease is too low to allow proper
      randomization. In this review, we have attempted to assess the indications and
      outcomes of AM transplantation based on 661 cases reported in the peer-reviewed
      literature. Successful outcome was defined as the healing of an epithelial defect
      (corneal or conjunctival) over a specified time period and the lack of induced
      motility disturbance.

PMID- 17216093
TI  - Thoughts generated by the annual meeting of the American Society of Clinical
      Pharmacology and Therapeutics.

PMID- 17216095
TI  - The Tear Film and Ocular Surface Society.

PMID- 17216094
TI  - Jules L. Baum, MD.

PMID- 17216097
TI  - Andrew de Roetth (1893-1981): dacryologist who introduced the term dry eye.

PMID- 17216099
TI  - Nerves and sensations from the eye surface.
AB  - Because vision plays a critical role in obtaining information from the external
      world, evolutionary development has provided the structures that sustain this
      function with special protection against injury. Thus, the cornea possesses the
      richest sensory innervation of the body to detect noxious stimuli. The trigeminal
      sensory neurons that innervate the eye vary in their chemical composition and
      electrophysiological properties, and can be classified according to the stimuli
      that activate them preferentially: mechanical forces, temperature, or irritant
      chemicals. Different classes of noxious stimuli (mechanical injuries, heat,
      extreme cold) activate to a different degree the various populations of sensory
      fibers of the ocular surface and evoke unpleasant sensations of distinct quality.
      When injured either accidentally or following ocular surgery, sensory nerve
      fibers of the ocular surface may form neuromas that develop abnormal activity and
      become the source of unpleasant sensations, such as pain, dryness, grittiness,
      etc. In parallel, their response to natural stimuli is diminished. The
      possibility of hypesthesia and dysaesthesias must be considered in the assessment
      of the risks of therapeutic procedures that involve damage to ocular sensory
      nerves.

PMID- 17216100
TI  - Punctal plugs in the management of dry eyes.
AB  - Punctal plugs appear to be a relatively safe, effective, and reversible method of
      preserving aqueous and artificial tears on the ocular surface to reduce the signs
      and symptoms of dry eye. An absorbable plug may be used temporarily to assess the
      effectiveness of this therapy prior to insertion of a longterm nonabsorbable plug
      (Freeman-type, Herrick Lacrimal Plug, or SmartPlug) or cautery. Indications and
      contraindications for use of punctal plugs are discussed, as are features of
      various plugs, techniques of insertion and removal, complications, and outcomes.

PMID- 17216101
TI  - What happens to patients at the end of the clinical trial?

PMID- 17216102
TI  - Pathways of corneal and ocular surface inflammation: a perspective from the
      cullen symposium.
AB  - The goal of this symposium was to coalesce information presented by 22
      investigators in the field of corneal and ocular surface inflammation into common
      pathways of inflammation. The perspective elucidated in this article defines the
      components of the normal ocular surface immune architecture and describes the
      consensus reached on the mechanisms/pathways involved in 1) acute inflammation;
      2) late-stage (chronic) response; and 3) allergic disease. Seven diagrams
      didactically illustrate mechanisms. This paper is the introductory article in a
      supplement containing 18 articles by the symposium participants.

PMID- 17216103
TI  - Inflammatory response to Pseudomonas aeruginosa keratitis.
AB  - Recent advances in our understanding of the inflammatory response to Pseudomonas
      aeruginosa (P. aeruginosa)-induced keratitis have revealed a critical role for
      the cytokine interleukin (IL)-1beta in up-regulation of other
      cytokines/chemokines and promoting neutrophil (PMN) infiltration. Studies using
      antibody neutralization, knockout of caspase-1 (ICE), the enzyme that processes
      IL-1beta from the pro- to the active form, as well as use of an inhibitor of the
      enzyme, have provided evidence that decreasing levels of IL-1beta in the cornea
      improves disease outcome. When combined with antibiotic, the caspase-1 inhibitor
      provided better disease outcome than either the inhibitor or antibiotic alone,
      supporting the possibility of alternate therapy for this disease.

PMID- 17216104
TI  - Cytokine profiles in conjunctival allergy and inflammation.
AB  - Identifying the cells and cytokines present at the ocular surface in different
      clinical subgroups of patients with conjunctival allergy and inflammation has led
      to an improved understanding of the immune-mediated mechanisms that occur.
      Together with the recent advances in immunotherapeutic interventions for various
      immune-mediated diseases, it is hoped that some of these will be applicable for
      the treatment of conjunctival inflammatory diseases in the near future.

PMID- 17216105
TI  - Variation in the expression of inflammatory markers and neuroreceptors in human
      conjunctival epithelial cells.
AB  - The purpose of this research was to investigate the role of neurogenic
      involvement in the etiopatho-genesis of ocular surface inflammation, with the
      final goal of identifying new potential anti-inflammatory agents. We describe the
      presence of two "classic" markers of inflammation (HLA-DR and ICAM-1) and some
      neuroreceptors in cultured human conjunctival epithelial cells under basal and
      pro-inflammatory conditions. Two markers of inflammation (HLA-DR, ICAM-1) and
      several neuroreceptor subtypes (M1-, M2-, and M3-muscarinic; alpha1A-, alpha1B-,
      alpha1D-, alpha2A-, alpha2B-, alpha2C-, beta1-, beta2-, and beta3-adrenergic)
      were analyzed in a normal human conjunctival epithelial cell line (IOBA-NHC).
      These markers were studied in basal conditions and under the influence of two pro
      inflammatory cytokines: tumor necrosis factor alpha (TNF-alpha) and/or interferon
      gamma (IFN-gamma). Immunofluorescence (confocal microscopy), western blotting, or
      flow cytometry techniques were used. In basal conditions, epithelial cells
      expressed all inflammatory markers except HLA-DR. The addition of IFN-gamma
      enhanced expression of HLA-DR, ICAM-1, and M2-muscarinic receptor. TNF-alpha up
      regulated the expression of ICAM-1. When epithelial cells were incubated in the
      presence of both cytokines together, the cell surface expression of HLA-DR, ICAM
      1, alpha1B-, and alpha2B-adrenergic receptors was increased. Cultured human
      conjunctival epithelial cells have been shown to be susceptible to up-regulation
      of the expression of inflammatory markers and cell membrane expression of some
      neuroreceptors under pro-inflammatory conditions. Consequently, pharmacologic
      neuro-modulation could have a role in the comprehensive management of ocular
      surface inflammation.

PMID- 17216106
TI  - Chemokine signaling pathways in corneal fibroblasts.
AB  - Chemokines act as leukocyte chemoattractants with fine specificity for individual
      leukocyte types. Chemokine activation in infectious and inflammatory conditions
      of the cornea has been well described and is thought to result from rapid
      activation of intracellular signaling cascades within corneal cells. Keratocytes,
      the resident cells of the corneal stroma, capably express a diverse array of
      chemokine family members. We describe the role of chemokines in corneal
      inflammation in both human disease and experimental animal models. Understanding
      the precise molecular signaling mechanisms for regulation of chemokine expression
      will be integral to the design of strategies for the reduction of detrimental
      corneal inflammation.

PMID- 17216098
TI  - Defensins and other antimicrobial peptides at the ocular surface.
AB  - Although constantly exposed to the environment and "foreign bodies" such as
      contact lenses and unwashed fingertips, the ocular surface succumbs to infection
      relatively infrequently. This is, in large part, due to a very active and robust
      innate immune response mounted at the ocular surface. Studies over the past 20
      years have revealed that small peptides with antimicrobial activity are a major
      component of the human innate immune response system. The ocular surface is no
      exception, with peptides of the defensin and cathelicidin families being detected
      in the tear film and secreted by corneal and conjunctival epithelial cells. There
      is also much evidence to suggest that the role of some antimicrobial peptides is
      not restricted to direct killing of pathogens, but, rather, that they function in
      various aspects of the immune response, including recruitment of immune cells,
      and through actions on dendritic cells provide a link to adaptive immunity. A
      role in wound healing is also supported. In this article, the properties,
      mechanisms of actions and functional roles of antimicrobial peptides are
      reviewed, with particular emphasis on the potential multifunctional roles of
      defensins and LL-37 (the only known human cathelicidin) at the ocular surface.

PMID- 17216107
TI  - Inflammatory response to fungal keratitis.
AB  - Ocular fungal infections occur worldwide and are important contributors to vision
      loss. While many aspects of the microbe and host interaction involved in fungal
      keratitis remain undefined, two aspects known to affect susceptibility are
      disruption of the epithelial barrier and immunosuppression of the host. Our
      recent pathogenesis studies using an experimental murine model have provided
      insight into the influence of these factors on keratomycosis. Increased
      susceptibility was associated with greater neutrophilic infiltration, greater
      fungal invasion of the corneal stroma, up-regulation of matrix metalloproteinase
      9, and morphogenic switching from yeast to hyphae. Understanding the pathogenic
      events of fungal keratitis will identify potential targets for therapeutic
      intervention of these sight-threatening infections.

PMID- 17216108
TI  - Stress-activated protein kinase signaling pathways in dry eye and ocular surface
      disease.
AB  - Inflammation is recognized as a key component in the pathogenesis of dry eye and
      a variety of ocular surface diseases. Stress-activated protein kinases have been
      identified as pathways signaling ocular surface stresses, such as increased tear
      film osmolarity and ultraviolet light exposure. Activation of these stress
      pathways results in transcription of stress related genes, including inflammatory
      cytokines (e.g. interleukin-1 and tumor necrosis factor (TNF)-alpha and matrix
      metalloproteinases (MMPs), such as MMP-9. Treatment of osmo-stressed cultured
      corneal epithelia with inhibitors of the stress associated kinase c-jun N
      terminal kinases was found to decrease production of MMPs by these cells. These
      findings suggest that SAPKs may be key therapeutic targets for dry eye and ocular
      surface diseases.

PMID- 17216109
TI  - Corneal immune privilege.
AB  - This year marks the 100th anniversary of the first successful corneal transplant
      on a human subject. Corneal allografts enjoy an exceptionally high acceptance,
      with rejection occurring in less than 10% of the patients who have not previously
      received a corneal transplant and who do not have underlying ocular inflammation.
      Corneal grafts survive even though HLA typing and systemic immunosuppressive
      drugs are not employed. The remarkable success of corneal transplants is due to a
      combination of anatomical, physiological, and immunological properties that
      conspire to prevent the induction and expression of potentially destructive
      immune responses to the foreign transplant.

PMID- 17216110
TI  - Evaluation of ocular surface inflammation in the presence of dry eye and allergic
      conjunctival disease.
AB  - The ocular inflammatory diseases dry eye and allergic conjunctivitis are mediated
      by CD4+ T cells. Th1 cells secrete interferon (IFN)-gamma and are implicated in
      mediating the disease process in dry eye. Allergic conjunctivitis has been
      classically defined as a Th2 disease because of the predominance of Th2 cytokines
      interleukin (IL)-4 and IL-13. A multi-hit antigen challenge mouse model of
      allergic conjunctivitis provides evidence that IFN-gamma, a Th1 cytokine, acts as
      an endothelium gatekeeper by regulating endothelial expression of vascular
      adhesion molecule-1 required for inflammatory conjunctival cell infiltration.
      Current research encourages an in-depth evaluation of the exact role Th1 and Th2
      cells play in ocular inflammation.

PMID- 17216111
TI  - Mechanisms of corneal allograft rejection.
AB  - More effective therapies are required to improve clinical corneal allograft
      outcomes. The strategies that have led to improvements in vascularized organ
      graft survival are not always applicable to the cornea. New treatments that
      modulate the afferent arm of the immune response to a corneal allograft are more
      likely to prove effective than are treatments that target the effector arm of the
      immune response. We briefly discuss two such options: the use of engineered
      antibody fragments to block antigen presentation, and the use of gene therapy
      approaches to abrogate antigen presenting-cell function.

PMID- 17216112
TI  - Corneal antigen presentation: molecular regulation and functional implications.
AB  - Presentation of corneal antigens for induction of adaptive immune responses is
      mediated by corneal antigen-presenting cells (APC), including those that
      infiltrate the cornea in response to inflammatory stimuli and, to a lesser
      extent, those that reside in the cornea and up-regulate activation markers in
      response to inflammation. Significant progress has been made in the last decade
      in dissecting the molecular mechanisms that mediate APC infiltration into the
      cornea. However, it has recently been determined that exit of APC out of the
      cornea is critical for induction of T cells that normally reside outside of the
      cornea in lymphoid reservoirs. Much less is understood about the molecular
      regulation of APC egress from the cornea, but our laboratory has recently
      discovered that APC access to afferent lymphatics and draining lymph nodes
      requires signaling mediated by VEGFR-3. We describe herein the functional
      implication of APC trafficking and the prospects for novel immunomodulatory
      strategies based on regulating APC migration.

PMID- 17216113
TI  - Neutrophil migration in the wounded cornea: the role of the keratocyte.
AB  - Neutrophil migration into the corneal stroma following epithelial injury is an
      early event in the non-adaptive immune response. Little is known regarding the
      molecular and cellular mechanisms that regulate neutrophil migration within the
      injured cornea. In this article, evidence is presented supporting the idea that
      migrating neutrophils form integrin-dependent adhesive contacts not only with
      extracellular matrix molecules, but also with interstitial cells known as
      keratocytes. Since keratocytes express adhesion molecules and secrete leukotactic
      factors, and because they are joined to one another to form a cellular network,
      we suggest that the keratocyte network plays a prominent role in neutrophil
      migration by serving as a source of contact guidance and chemoattraction for
      migrating neutrophils. The proposed neutrophil interactions with keratocytes
      constitute the beginning of a new experimental paradigm for understanding
      leukocyte migration within the injured cornea.

PMID- 17216114
TI  - Ocular graft vs. host disease.
AB  - Acute graft vs host disease (GVHD) is thought to be mainly a Th1 inflammatory
      mediated process, whereas chronic GVHD involves primarily Th2 inflammation. To
      elucidate new strategies for the treatment and prevention of ocular GVHD, it is
      important to understand the pathophysiologic connection between systemic and
      organ-specific acute and chronic GVHD. The two types of inflammatory processes,
      however, represent only a part of a highly intricate, complex disorder. Studies
      to further understand the inflammatory profile of ocular GVHD are ongoing.

PMID- 17216115
TI  - Influence of the eye-associated lymphoid tissue (EALT) on inflammatory ocular
      surface disease.
AB  - Certain similarities exist in the pathophysiological processes and clinical
      features of advanced stages of various inflammatory ocular surface diseases,
      suggesting that common pathways contribute to these diseases. In this article,
      common pathways are analyzed with a focus on the role of the physiological
      resident mucosal immune system of the ocular surface, termed eye-associated
      lymphoid tissue (EALT). This is physiologically protective but if it is
      deregulated it can mediate an inflammatory immune answer. Common events in
      inflammatory ocular surface disease lead to a vicious circle of immune-modulated
      inflammation, with degenerative remodeling and loss of function.

PMID- 17216116
TI  - Toll-like receptors in the cornea.
AB  - We propose that activation of Toll-like receptors (TLRs) in the corneal
      epithelium in response to exposure to microbial products leads to production of
      CXC chemokines and recruitment of neutrophils to the stroma, increasing stromal
      thickness and causing haze. A schematic is presented showing the proposed role of
      TLRs in the inflammatory process.

PMID- 17216117
TI  - Modulation of corneal vascularization.
AB  - Avascularity of normal cornea is a result of homeostasis between anti-angiogenic
      and pro-angiogenic stimuli. Disruption of this delicate balance during corneal
      wound healing can lead to pathological corneal vascularization. Several unique
      characteristics in the ocular surface epithelia modulate corneal avascularity.
      Normal cornea contains heparan sulfate to prevent the release of potent
      angiogenic cytokines, such as basic fibroblast growth factor (bFGF) from the
      Bowman's layer. Potent angiostatic factors, such as endostatin and angiostatin,
      can be produced from degradation of corneal extracelluar matrix. In contrast,
      conjunctiva contains angiogenic cytokines, such as bFGF and vascular endothelial
      growth factor. In addition to regulating release of angiogenic and angiostatic
      cytokines, matrix metalloproteinases (MMPs) and other proteolytic enzymes can
      modulate corneal vascularization via matrix degradation to allow endothelial
      migration and tissue remodeling. When the cornea becomes vascularized,
      inflammatory cells and mediators gain uninhibited access to the cornea, thus
      rendering immune sensitization and increased risk of corneal graft rejection.
      Novel therapies targeting angiogenic cytokines or MMPs have been shown to
      suppress corneal vascularization effectively in animal models, and may have
      therapeutic potential for clinical use.

PMID- 17216118
TI  - Amplifying factors in ocular surface diseases: apoptosis.
AB  - Apoptosis is a major cell death mechanism that occurs widely in normal tissues
      and is overstimulated in ocular surface diseases. Apoptosis has been studied
      specifically in regard to refractive surgery, contact lens wear, and dry eye
      syndrome. It appears to be closely related to inflammation, as many inflammatory
      cytokines may promote both inflammation and apoptosis, and their receptors
      trigger both pathways. A major mediator would play a key role in ocular surface
      diseases, both at the pro-apoptotic and pro-inflammatory levels, e.g., tumor
      necrosis factor alpha. This cytokine and its main receptors are, therefore,
      overexpressed in ocular surface diseases, which makes it a possible target for
      future therapeutic approaches.

PMID- 17216119
TI  - Matrix metalloproteinases in corneal inflammation.
AB  - Matrix metalloproteinases (MMPs) are a family of calcium-dependent, zinc
      containing endoproteinases capable of degrading the extracellular matrix and
      basement membrane. Many inflammatory stimuli, such as wound healing, ultraviolet,
      hyperosmolarity, and stress, can stimulate production of inflammatory cytokines
      and a variety of MMPs, including gelatinases, collagenases, and stromelysins. Pro
      inflammatory cytokines and growth factors can further promote the production of
      MMPs. Thus, MMPs participate in and promote the inflammation process. MMP-9 may
      be a most important amplifying factor for corneal inflammation. Mitogen activated
      protein kinases are involved in MMPs amplified inflammation. These pathway
      studies provide new therapeutic potential to block MMP mediated inflammation.

PMID- 17216120
TI  - Neurogenic inflammation: a first line of defense for the ocular surface.
AB  - Neurogenic inflammation and innate immunity may work together to protect mucosal
      surfaces, including the ocular surface. When the eye is exposed to pathogens,
      chemical irritants, or mechanical disruption, neurogenic inflammation is produced
      through release of neuromodulators, such as substance P and calcitonin gene
      related peptide. This leads to the breakdown of the blood-tissue barrier, edema,
      and release of polymorphonuclear leukocytes into the tears, thus allowing
      intervention of systemic immunity. Neurogenic mechanisms may have a significant
      role in the onset and chronicity of ocular surface inflammation in conditions
      such as dry eye.

PMID- 17216121
TI  - Inguinal hernia repair: the choice of prosthesis outweighs that of technique.
AB  - BACKGROUND: The use of prostheses in inguinal hernia repair reduces the incidence
      of recurrence. Quality of life and pain after hernia repair are largely
      correlated with the technique and type of prosthesis. AIMS OF STUDY: To evaluate
      the 2-year incidence of recurrence and pain for two types of hernioplasty,
      Lichtenstein repair and laparoscopy (totally extraperitoneal approach or TEP),
      and two types of mesh, polypropylene mesh and beta-D: -glucan-coated mesh
      (Glucamesh). PATIENTS: A total of 410 consecutive patients of mean age 54 years
      (18-84) underwent repair of inguinal hernias, 96 (23%) of which were bilateral
      and 56 (13%) recurrent. A total of 273 (66.5%) patients underwent Lichtenstein
      repair: 215 (78.7%) with polypropylene mesh, 58 (21.3%) with Glucamesh; 137
      patients underwent laparoscopy: 80 (58.4%) with polypropylene mesh, 57 (41.6%)
      with Glucamesh. In each group, the populations were comparable and the techniques
      utilized were identical. METHODS: The patients were followed-up for at least 2
      years, after which the incidence of recurrence was determined, and chronic pain
      was assessed by means of a visual analog scale and a validated questionnaire.
      RESULTS: A total of 349 patients (85.1%) were reassessed, 117 of whom had
      undergone laparoscopy and 232 Lichtenstein repair. There were ten recurrences
      (2.8%), and incidence which was independent of the technique (laparoscopy 1.7%
      vs. Lichtenstein 3.4%) (ns) and the type of prosthesis (Glucamesh 1.9% vs.
      polypropylene 2.4%) (ns). Chronic pain was noted in 69 patients (19.7%) and
      severe pain in 11 (3.1%). The incidence of chronic pain was the same for the two
      techniques: laparoscopy 17.9% vs. Lichtenstein 20.7% (ns). The same was true for
      severe pain: laparoscopy 3.4% vs Lichtenstein 3% (ns). The incidence of chronic
      pain was closely correlated with the type of prosthesis utilized: Glucamesh 4.8%
      vs. polypropylene 26.5% (P = 0.02), irrespective of the technique. The same was
      true for severe pain (0.9 vs. 4%) (P = 0.02). CONCLUSION: The utilization of beta
      D: -glucan-coated mesh did not involve more recurrence and was accompanied by a
      significant decrease in chronic pain at 2 years, independent of the technique.
      After 2 years, the results of hernia repair show that the choice of prosthesis
      was more determinant than choice of technique.

PMID- 17216122
TI  - Decision analysis model of incisional hernia after open abdominal surgery.
AB  - BACKGROUND: The incidence rate of incisional hernias after open surgery has been
      reported to be higher than that of port site hernias after laparoscopic surgery.
      No studies have compared the costs for the health care system in treating those
      two types of hernia. METHODS: A systematic review was conducted to obtain the
      baseline data, and a decision analysis model was created to simulate the
      occurrence and recurrence of incisional and port site hernias. RESULTS: The
      overall risk of having incisional hernias was eight-times higher than that of
      having port site hernias (7.4% vs 0.9%). A cost savings of 93 British Pound per
      patient can be generated for the health care system in the UK. Similar results
      were obtained for Germany, Italy and France. CONCLUSIONS: The additional
      treatment costs for incisional hernia should be taken into account when the costs
      of a surgery performed by open approach are compared with by laparoscopy.

PMID- 17216123
TI  - Can late gadolinium enhancement by cardiovascular magnetic resonance identify
      coronary artery disease as the etiology of new onset congestive heart failure?
AB  - BACKGROUND: New left ventricular systolic dysfunction affects 500,000 Americans
      and coronary artery disease (CAD) is responsible for two-thirds of cases.
      Identifying CAD has both prognostic and therapeutic implications. We evaluated
      the ability of late gadolinium enhancement (LGE) by cardiovascular magnetic
      resonance imaging (CMR) to detect CAD as the etiology of recent onset congestive
      heart failure (CHF). METHODS: CMR and LGE were performed in 26 patients with new
      onset left ventricular systolic dysfunction. All patients received an x-ray
      angiography for identification of CAD. Patients with an acute coronary syndrome
      with troponin I > 1.0 ng/ml or a history of CAD were excluded. The presence and
      distribution of LGE was evaluated. RESULTS: Significant coronary stenoses were
      present in 5 of 26 patients (19%). LGE in an infarct pattern was found in 2 of
      the 5 patients with CAD. Of the 21 patients without CAD, 2 had midwall
      enhancement but none had evidence of LGE in an infarct pattern. CONCLUSIONS: When
      present, LGE in an infarct pattern suggests CAD as the etiology of new onset CHF.
      However, the absence of LGE does not exclude CAD as the underlying etiology. A
      small proportion of patients with a nonischemic cause of new onset CHF have LGE
      limited to the midwall.

PMID- 17216124
TI  - Redefining the normal angiogram using population-derived ranges for coronary size
      and shape: validation using intravascular ultrasound and applications in diverse
      patient cohorts.
AB  - OBJECTIVES: To develop a method for quantitating coronary angiographic
      abnormalities of segmental size and shape (tapering) in comparison to gender- and
      segment-specific, population derived, normal values. BACKGROUND: In the absence
      of obvious focal stenoses, remodeling renders the angiogram insensitive to the
      presence of atherosclerosis and invalidates use of a "normal reference segment"
      for calculation of percent diameter stenosis. METHODS: Equations were created for
      detection of size/shape abnormalities of coronary angiographic segments. After
      validation using intravascular ultrasound (IVUS), the equations were applied to a
      cohort of segments judged to be completely normal by a panel of highly
      experienced, core laboratory technicians; and a cohort of patients judged by an
      experienced interventionalist to have completely normal coronaries. RESULTS: In
      patients assessed by core technicians, 53% (162/303) of males, 39% (209/538) of
      normal segments in males, 60% (56/94) of females, and 40% (81/205) of normal
      segments in females had quantifiable abnormalities. In patients with normal
      coronaries as judged by an experienced interventionalist, 100% of males (n = 14)
      and females (n = 19), 37% (67/182) of segments in males and 43% (105/247) of
      segments in females had abnormalities. The left main segment was most commonly
      abnormal. CONCLUSIONS: We propose a set of equations validated using IVUS and
      based on gender- and segment-specific normal values for coronary angiographic
      size and shape that markedly improves the sensitivity of the coronary angiogram
      for detection of abnormalities. The method should replace the unfounded practice
      of labeling coronary angiograms as "normal" based solely on the failure to detect
      focal stenoses.

PMID- 17216125
TI  - Accuracy and rate of coronary artery segment visualization with CT angiography
      for the non-invasive detection of coronary artery stenoses.
AB  - OBJECTIVES: To evaluate CT coronary angiography (CTA) when compared with catheter
      coronary angiography (CCA), for the detection of coronary artery stenoses and
      rate of optimal coronary artery segment visualization. METHOD: Retrospective, two
      center study enrolling 26 patients who underwent CCA and ECG-gated 16-detector
      CTA (slice thickness 0.6 mm; rotation 500 ms). RESULTS AND CONCLUSION: 283
      segments were available for postprocessing. Sensitivity, specificity, and
      positive predictive value were, respectively, 80, 100, and 100%, for detecting
      more than 50% luminal stenoses, when optimally visualized segments were
      considered, in comparison to CCA. Negative predictive value was excellent (98%).
      Rate of non-optimally visualized coronary segments was 26%. Most clinical
      benefits of coronary CT angiography should probably be obtained when it is
      performed to exclude significant stenoses on selected populations of patients
      with a low pre-test probability of severe coronary artery disease, and under
      optimal conditions of controlled heart rate and minimal presence of calcium.

PMID- 17216126
TI  - Tortuosity of coronary arteries: an indicator for impaired left ventricular
      relaxation?
AB  - OBJECTIVE: To investigate the relationship between coronary tortuosity and
      impaired left ventricular relaxation. METHODS: One hundred and four subjects who
      underwent coronary angiography were included in the study. Left anterior
      descending, left circumflex, and right coronary arteries were traced. Tortuosity
      was identified by the finding of >/=3 bends (defined as >/=45 degrees change in
      vessel direction) along main trunk of at least one artery. Study population were
      divided into tortuosity (n = 54) and no tortuosity (n = 50) groups. Subjects were
      all submitted to pulsed-wave Doppler and two-dimensional echocardiographic
      examination to assess left ventricular functions. RESULTS: For subjects with
      tortuosity, early transmitral inflow (E) velocity was lower, late transmitral
      inflow (A) velocity was higher, E/A ratio was smaller compared with subjects
      without tortuosity (P < 0.001). Subjects with tortuosity had longer deceleration
      time of E velocity (DT) and isovolumic relaxation time (IVRT) than did subjects
      without tortuosity (P < 0.001). End-diastolic interventricular septal and left
      ventricular posterior wall thicknesses were greater in subjects with tortuosity
      than those without tortuosity (P = 0.01 and P = 0.005). There was an inverse
      correlation between total number of arteries with tortuosity and E/A ratio (r = 
      0.750, P < 0.001). Total number of arteries with tortuosity displayed
      correlations with DT (r = 0.723, P < 0.001) and IVRT (r = 0.703, P < 0.001).
      CONCLUSIONS: This study depicts that coronary tortuosity is associated with
      impaired left ventricular relaxation.Thus, coronary tortuosity might be an
      indicator of impaired left ventricular relaxation.

PMID- 17216127
TI  - In-vitro cytotoxic and genotoxic effects of arsenic trioxide on human leukemia
      (HL-60) cells using the MTT and alkaline single cell gel electrophoresis (Comet)
      assays.
AB  - Although arsenic trioxide (ATO) has been the subject of toxicological research,
      in vitro cytotoxicity and genotoxicity studies using relevant cell models and
      uniform methodology are not well elucidated. Hence, the aim of the present study
      was to evaluate the cytotoxicity and genotoxicity induced by ATO in a human
      leukemia (HL-60) cell line using the MTT [3-(4, 5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide] and alkaline single cell gel electrophoresis (Comet)
      assays, respectively. HL-60 cells were treated with different doses of ATO for 24
      h prior to cytogenetic assessment. Data obtained from the MTT assay indicated
      that ATO significantly (P < 0.05) reduced the viability of HL-60 cells in a dose
      dependent manner, showing a LD(50) value of 6.4 +/- 0.6 microg/mL. Data generated
      from the comet assay also indicated a significant dose-dependent increase in DNA
      damage in HL-60 cells associated with ATO exposure. We observed a significant
      increase (P < 0.05) in comet tail-length, tail arm and tail moment, as well as in
      percentages of DNA cleavage at all doses tested, showing an evidence of ATO
      induced genotoxic damage in HL-60 cells. This study confirms that the comet assay
      is a sensitive and effective method to detect DNA damage caused by heavy metals
      like arsenic. Taken together, our findings suggest that ATO exposure
      significantly (P < 0.05) reduces cellular viability and induces DNA damage in HL
      60 cells as assessed by MTT and alkaline single cell gel electrophoresis assays,
      respectively.

PMID- 17216128
TI  - Association of LKB1 with a WD-repeat protein WDR6 is implicated in cell growth
      arrest and p27(Kip1) induction.
AB  - Germline mutations of the serine/threonine kinase LKB1 (also known as STK11) lead
      to Peutz-Jeghers syndrome (PJS) that is associated with increased incidence of
      malignant cancers. However, the tumor suppressor function of LKB1 has not been
      fully elucidated. We applied yeast two-hybrid screening and identified that a
      novel WD-repeat protein WDR6 was able to interact with LKB1. Immunofluorescence
      staining revealed that WDR6 was localized in cytoplasm, similar to the
      localization of LKB1. Expression of LKB1 was able to inhibit colony formation of
      Hela cells. Interestingly, coexpression of WDR6 with LKB1 enhanced the inhibitory
      effect of LKB1 on Hela cell proliferation. Consistently, WDR6 was able to
      synergize with LKB1 in cell cycle G1 arrest in Hela cells. Coexpression of WDR6
      and LKB1 was able to induce a cyclin-dependent kinase (CDK) inhibitor p27(Kip1).
      Furthermore, the stimulatory effect of LKB1 on p27(Kip1) promoter activity was
      significantly elevated by coexpression with WDR6. Collectively, these results
      provided initial evidence that WDR6 is implicated in the cell growth inhibitory
      pathway of LKB1 via regulation of p27(Kip1).

PMID- 17216129
TI  - Time trends of mortality after first hip fractures.
AB  - A register-based study including 2,674 first hip fracture patients from 1987-1996
      investigated if the mortality after hip fracture was associated with time trend
      and fracture type. Despite significantly increasing age at admission no changing
      time trend of mortality was observed, nor was the mortality linked to the kind of
      fracture suffered. INTRODUCTION AND HYPOTHESIS: A retrospective cohort study was
      performed to investigate if the mortality of first hip fracture patients was
      associated with time trend and fracture type. The hypotheses were that cumulative
      mortality would remain unchanged and there would be no difference in mortality
      between cervical and pertrochanteric patients. METHODS: Study material was
      obtained by record linkage of excerpts from two computerized national health
      registers. First hip fractures were identified indirectly by searching the files
      ten years before the date of admission. The period 1987-1996 saw inclusion of
      2,674 patients aged 50 years and older (average follow-up 2.6 years). STATISTICS:
      Weighted regression analysis, chi(2) test, and t test. RESULTS: Cumulative
      mortality did not change significantly (P > 0.05). Weighted average cumulative
      mortality was 9% (95% CI, 7.9-10.1) at 1 month, 15.5% (95% CI, 14.1-16.8) at 3
      months, 26.5% (95% CI, 24.7-28.3) at 1 year, and 36.2% (95% CI, 34.1-38.3) at 2
      years. Cervical and pertrochanteric first hip fracture patients did not have
      significantly different mortality rates (P > 0.05). CONCLUSION: No changing time
      trend of mortality after first hip fracture was observed despite significantly
      increasing age at admission, nor was the mortality linked to the kind of fracture
      suffered.

PMID- 17216130
TI  - Osteoclasts prefer aged bone.
AB  - We investigated whether the age of the bones endogenously exerts control over the
      bone resorption ability of the osteoclasts, and found that osteoclasts
      preferentially develop and resorb bone on aged bone. These findings indicate that
      the bone matrix itself plays a role in targeted remodeling of aged bones.
      INTRODUCTION: Osteoclasts resorb aging bone in order to repair damage and
      maintain the quality of bone. The mechanism behind the targeting of aged bone for
      remodeling is not clear. We investigated whether bones endogenously possess the
      ability to control osteoclastic resorption. METHODS: To biochemically distinguish
      aged and young bones; we measured the ratio between the age-isomerized betaCTX
      fragment and the non-isomerized alphaCTX fragment. By measurement of TRACP
      activity, CTX release, number of TRACP positive cells and pit area/pit number, we
      evaluated osteoclastogenesis as well as osteoclast resorption on aged and young
      bones. RESULTS: We found that the alphaCTX/betaCTX ratio is 3:1 in young compared
      to aged bones, and we found that both alpha and betaCTX are released by
      osteoclasts during resorption. Osteoclastogenesis was augmented on aged compared
      to young bones, and the difference was enhanced under low serum conditions. We
      found that mature osteoclasts resorb more on aged than on young bone, despite
      unchanged adhesion and morphology. CONCLUSIONS: These data indicate that the age
      of the bone plays an important role in controlling osteoclast-mediated
      resorption, with significantly higher levels of osteoclast differentiation and
      resorption on aged bones when compared to young bones.

PMID- 17216131
TI  - Influence of fall related factors and bone strength on fracture risk in the frail
      elderly.
AB  - INTRODUCTION: When subjects are selected on the basis of fall risk alone,
      therapies for osteoporosis have not been effective. In a prospective study of
      elderly subjects at high risk of falls, we investigated the influence of bone
      strength and fall risk on fracture. METHODS: At baseline we assessed calcaneal
      bone ultrasound attenuation (BUA) as well as quantitative measures of fall risk
      in 2005 subjects in residential care. Incident falls and fractures were recorded
      (median follow-up 705 days). RESULTS: A total of 6646 fall events and 375 low
      trauma fracture events occurred. The fall rate was 214 per 100 person years and
      the fracture rate 12.1 per 100 person years. 82% of the fractures could be
      attributed to falls. Although fracture rates increased with decreasing BUA
      (incidence rate ratio 1.94 for lowest vs. highest BUA tertile, p<0.002), incident
      falls also affected fracture incidence. Subjects who fell frequently (>3.15
      falls/per person year) were 3.35 times more likely to suffer a fracture than
      those who did not fall. Some fall risk factors such as balance were associated
      with the lowest fracture risk lowest in the worst performing group. Multivariate
      analysis revealed higher fall rate, history of previous fracture, lower BUA,
      lower body weight, cognitive impairment and better balance as significant
      independent risk factors for fracture. CONCLUSIONS: In the frail elderly, both
      skeletal fragility and fall risk including the frequency of exposure to falls are
      important determinants of fracture risk.

PMID- 17216132
TI  - A nomogram for predicting osteoporosis risk based on age, weight and quantitative
      ultrasound measurement.
AB  - INTRODUCTION: Quantitative ultrasound measurement (QUS) or clinical risk index
      alone are not reliable tools for the identification of women with osteoporosis.
      This study examined the prognostic value of combined QUS and clinical risk index
      for predicting osteoporosis risk in Thai women. METHODS: The study was designed
      as a cross-sectional investigation with 300 women of Thai background, aged
      between 38 and 85 years (mean age: 58). Femoral neck bone mineral density (BMD)
      was measured by DXA (Hologic QDR-4500; Bedford, MA, USA). A femoral neck BMD T
      scores <or= -2.5 was defined as "osteoporosis"; otherwise, "non-osteoporosis".
      QUS was measured by Achilles+ (GE Lunar, Madison, WI, USA) and converted to T
      score. Three models for predicting osteoporosis were considered: model I included
      age, weight and QUS, model II included age and weight, and model III included
      only QUS. The prognostic performance among the models was assessed by the area
      under the receiver operating characteristic curve (AUC). RESULTS: The prevalence
      of osteoporosis was 12.7% (n=38/300) by femoral neck BMD. Age, weight and QUS
      were each significantly associated with osteoporosis risk. The AUC+/-SE value for
      model I was 0.86 +/- 0.03, which was significantly higher (p=0.02) than that for
      model II (AUC = 0.80 +/- 0.04) or model III (AUC = 0.79 +/- 0.04). Based on the
      estimated parameters of model I, a nomogram was constructed for predicting
      osteoporosis. CONCLUSION: These data suggest that the combination of QUS and age
      and weight could significantly improve the prognosis of osteoporosis in Asian
      women, and that the nomogram can assist primary care physicians in the
      identification of high-risk women.

PMID- 17216133
TI  - A long-term review of posterior colporrhaphy with Vypro 2 mesh.
AB  - The objective is to study the long-term outcomes of posterior colporrhaphy with
      composite polyglactin 910-polypropylene mesh (Vypro 2, Ethicon, Somerville, NJ,
      USA) utilizing an overlay technique. Seventy-eight patients involved in our
      previous study were contacted 3 years after their initial operation for follow-up
      (Lim YN, Rane A, Muller R, Int Urogynecol J 16:126-131, 2005). Thirty-seven (47%)
      returned for follow-up and completed a standardized questionnaire survey, whereas
      a further 16 (20%) returned their postal questionnaires. Mean age was 61.3 (SD
      10.8) years, and follow-up was 35.7 (SD 4.5) months. There were statistically
      significant improvements in vaginal lump sensation and constipation (p < 0.001)
      but no differences with defecatory difficulties or dyspareunia. De novo
      dyspareunia was reported in 27%. On examination, the incidences of mesh vaginal
      erosion and rectocele recurrence were 30% and 22%, respectively. It appears that
      posterior colporrhaphy incorporating Vypro 2 mesh with an overlay method is
      associated with unacceptably high incidence of complications.

PMID- 17216134
TI  - Evidence that Cymbidium mosaic virus (CymMV) isolates divide into two subgroups
      based on nucleotide diversity of coat protein and replicase genes.
AB  - The genetic diversity of Cymbidium mosaic virus (CymMV, family Flexiviridae) was
      assessed by analysing the nucleotide sequences of coat protein (CP) and partial
      RNA-dependent RNA polymerase (RdRp) genes. Thirty CymMV sequences from vanilla
      isolates, obtained in this work by direct sequencing of RT-PCR products, were
      compared to the sequences from ornamental orchid isolates available in GenBank.
      The CymMV population exhibited overall low genetic diversity (pi=0.054 and
      pi=0.053 for CP and RdRp genes, respectively). Phylogenetic analyses of the 85 CP
      and 37 RdRp sequences revealed the segregation of the isolates into two congruent
      monophyletic clusters; however these two subgroups did not cluster in amino
      sequence analysis because most of the nt mutations were synonymous. Nevertheless,
      the subgrouping was confirmed by highly significant Kst tests for the CP and RdRp
      genes. Analysis of population genetic parameters and distribution of synonymous
      and nonsynonymous mutations revealed that both genes were under negative
      selection with no recombination events. These results suggested that the CymMV
      isolates found in cultivated orchids worldwide have a dual origin and are
      expanding as if following bottlenecks.

PMID- 17216135
TI  - Genetic stability of recombinant potato virus X virus vectors presenting foreign
      epitopes.
AB  - We investigated the genetic stability of recombinant potato virus X vectors
      presenting beet necrotic yellow vein virus (BNYVV) epitopes. Following N-terminal
      PVX coat protein (CP) fusion of the BNYVV epitopes, we inoculated Nicotiana
      benthamiana plants with recombinant (r)PVX and carried out five serial passages
      through systemically-infected plants. RT-PCR investigation of the BNYVV epitope
      sequences revealed the accumulation of several point mutations and deletions,
      predominantly affecting positively-charged residues. A comparison of the
      isoelectric point (pI) values and charges of the wild type and rCPs showed that
      the initial high rCP pI values had changed to values closer to that of the wild
      type CP.

PMID- 17216136
TI  - Coming to grips with the naming of viruses; continuing discord, or a way out?

PMID- 17216137
TI  - Genetic structure in natural populations of barley/cereal yellow dwarf virus
      isolates from Alaska.
AB  - The genetic structure of natural populations of Alaskan barley yellow dwarf virus
      (BYDV)-PAV, BYDV-PAS, and cereal yellow dwarf virus (CYDV)-RPV from barley
      (Hordeum vulgare L.) and oats (Avena sativa L.) in Alaska were analyzed between
      2002 and 2004. PCR products spanning the viral coat protein gene of 187 isolates
      were cloned and sequenced. The majority (78%) were similar to BYDV-PAS, 19% were
      similar to CYDV-RPV, and only about 3% resembled BYDV-PAV. The CYDV-RPV isolates
      clustered in three groups: 44, 17, and 39% resembled RPS-like CP from Mexico,
      resembled RPV-like CP from New York, or formed a unique clade that was RPV/RPS
      recombinant CP, respectively. The patterns of genetic variation of PAS and RPV
      varied little over time or with respect to host plant. The difference in spatial
      and temporal population genetic structures of the PAS and RPV isolates suggests
      that these two viruses are influenced by different agroecological factors.
      Sequence of PCR products spanning the carboxyl terminus of the polymerase gene,
      the intergenic region, and most of the coat protein gene of RPV revealed two
      probable ancestral recombination events for some isolates.

PMID- 17216138
TI  - Sequence determination and functional analysis of the Akabane virus (family
      Bunyaviridae) L RNA segment.
AB  - Akabane virus (AKAV) causes epizootic congenital deformities in cattle, sheep,
      and goats. Due to the lack of a complete genome sequence, the molecular
      biological properties of this virus are not known. We have cloned and sequenced
      the functional large (L) RNA segment of AKAV, and shown that it has polymerase
      activity using a minireplicon system with RNA polymerase I. The complete L RNA
      segment is 6868 nucleotides long and encodes an L protein of 2251 amino acids,
      which functions as an RNA-dependent RNA polymerase. A minireplicon reporter
      plasmid was constructed by flanking either the firefly luciferase or the green
      fluorescent protein gene in the antisense orientation with the 5'- and 3'
      terminal noncoding regions of the small RNA segment. HmLu-1 cells were
      transfected with the reporter plasmid, and the L protein and nucleoprotein (N
      protein) expression plasmids. The reporter activity was upregulated in a dose
      dependent manner with increasing concentration of either the L or N protein
      expression plasmid. Furthermore, the reporter activity could be downregulated by
      the AKAV NSs protein as well as by other orthobunyaviruses. These results show
      that the AKAV minireplicon system is a powerful tool for studying transcription
      and for rescuing infectious viruses from cloned cDNAs.

PMID- 17216139
TI  - Non-compact nucleocapsid protein multimers in influenza-virus-infected cells.
AB  - We have previously shown that protease-resistant and highly immunoreactive
      compact NP oligomers, dissociating at +80 degrees C and possessing properties of
      folded proteins, are post-translationally formed in influenza-virus-infected
      cells. In this study we demonstrate that, in addition to compact NP oligomers,
      incompletely folded NP multimers are detected intracellularly by SDS/PAGE carried
      out under weak dissociating conditions. In cells infected with avian, human
      A(H2N2), and human A(H3N2) viruses, NP multimers are detected in the stacking gel
      of SDS/PAGE as retarded and loose structures dissociating at +50 degrees C. NP
      multimers are more sensitive to proteolysis than NP oligomers, but they are more
      resistant to proteolysis than NP monomers. In contrast to compact NP oligomers,
      NP multimers possess a weak immunoreactivity to some monoclonal antibodies. Pulse
      chase experiments have shown that NP multimers appear at early stages of NP
      synthesis and are partially converted post-translationally into faster-migrating
      compact NP oligomers. In the course of infection, the excess NP multimers not
      converted into compact NP oligomers accumulate in cells and degrade. Under weak
      dissociating conditions, intracellular NP multimers are relatively stable in
      avian, human A(H2N2) and human A(H3N2) viruses and unstable in human A(H1N1)
      viruses, dissociating into monomers. NP multimers presumably serve to bring
      nascent unfolded NP molecules into close contact with each other for further
      oligomerization, to protect NP monomers from proteolysis, and to serve as
      intermediates in the posttranslational folding of NP.

PMID- 17216140
TI  - Predominance of hepatitis B virus genotype C among Karens, the 'old settlers' of
      Andaman and Nicobar Islands, India.
AB  - The Karens, or 'old settlers', migrated from Myanmar to Andaman and Nicobar
      islands 80 years ago. A high HBV exposure rate among them has been reported. A
      study of 34 HBsAg carriers was done to investigate the origin of HBV infection
      among the Karens. RFLP-based genotyping was confirmed by sequencing and
      phylogenetic analysis. The predominance of HBV/C1/Cs suggests that they carried
      HBV during their migration, retained it, and in addition, acquired HBV/D2 from
      the people of mainland India. The reported association of HBV genotype C with
      disease severity thus warrants further epidemiological investigations among them
      and on possible spread among neighboring settlers.

PMID- 17216141
TI  - Antitumor necrosis factor-alpha therapy for early postoperative recurrence of
      gastrointestinal Behcet's disease: report of a case.
AB  - Behcet's disease is a chronic, relapsing, systemic inflammatory disease
      characterized by recurrent oral and genital ulcers, skin lesions, and ocular
      lesions. Gastrointestinal tract is occasionally involved in Behcet's disease, and
      the typical gastrointestinal lesions are punched-out, discrete mucosal
      ulcerations. Corticosteroids, 5-aminosalicylic acid derivatives, thalidomide, and
      immunomodulators have been used to treat Behcet's disease. Some patients with
      gastrointestinal Behcet's disease undergo surgical management because of the
      refractoriness to these medical measures or complications, such as perforation
      and bleeding. Even after successful surgery, postoperative complications, such as
      poor healing of the anastomosis site and postoperative ulcer recurrence, are so
      common that repeated operations are frequently required. However, there have been
      few reports addressing the most effective way to reduce and treat postoperative
      complications and recurrences. We describe a patient with Behcet's disease
      involving the distal ileum, who was treated with infliximab as rescue therapy of
      an unhealed anastomosis site and early recurrent ulcers after a distal
      ileocecectomy because of persistent bleeding. Abdominal pain from recurrent
      ulcers improved by the fifth day after the infliximab infusion and almost
      disappeared by the second week. An ileocolonoscopy performed 15 days after the
      infliximab infusion showed near complete healing of the recurrent ulcers. This
      report suggests that infliximab may be an effective novel therapy for the
      management of early postoperative complications and recurrences in
      gastrointestinal Behcet's disease.

PMID- 17216142
TI  - The effect of octreotide on healing of injured colonic anastomosis with immediate
      postoperative intraperitoneal administration of 5-Fluorouracil.
AB  - PURPOSE: This study was designed to investigate the effect of octreotide on side
      effects of immediate usage of 5-fluorouracil after colonic anastomosis. METHODS:
      Forty male Wistar rats were randomly assigned into four groups and underwent
      standardized left colonic anastomosis. The rats served as control or received
      intraperitoneal 5-fluorouracil (20 mg/kg daily), subcutaneous octreotide (20
      mug/kg daily), or both. Diarrhea and wound complications were noted during the
      experiment. The colonic anastomoses were assessed for healing on postoperative
      Day 7 by determining the anastomotic bursting pressure, performing histologic
      examination, and measuring the tissue hydroxyproline content, serum
      malondialdehyde, and nitric oxide levels. Intraperitoneal adhesions and
      anastomotic leakage were also noted. RESULTS: No statistical significant
      difference was found between the control and octreotide groups for each of the
      parameters measured. Immediate 5-fluorouracil use resulted with higher adhesion
      score (P = 0.002), significant depression in anastomotic bursting pressure (P =
      0.0001), histopathologic score (P = 0.0001), hydroxyproline content (P = 0.0001),
      and increasing nitric oxide (P = 0.0001) and malondialdehyde levels (P = 0.0001)
      compared with the control group. Diarrhea was seen in 80 percent of the 5
      fluorouracil group but in neither the control nor octreotide groups (P = 0.0001
      for each comparison). However, all these parameters were ameliorated by use of
      concomitant octreotide and 5-fluorouracil (P = 0.019, P = 0.023, P = 0.0001, P =
      0.006, P = 0.0001, and P = 0.013, respectively). In addition, diarrhea was found
      to be prevented (P = 0.0001). CONCLUSIONS: The results of this study showed that
      concomitant octreotide use might prevent the side effects of 5-fluorouracil, such
      as diarrhea, postoperative adhesion, and delaying the anastomotic healing
      parameters. In addition, it might reduce tissue damage and inflammation.

PMID- 17216143
TI  - Assistance of colorectal stent insertion by sphincterotome.
AB  - PURPOSE: Palliation of patients with unresectable colorectal carcinoma is an
      effective treatment and technical failure is undesirable. Insertion of colorectal
      stent using a combined radiologic and colonoscopic technique may be technically
      limited by the ability to negotiate tortuous bends, particularly if the bowel is
      fixed. METHODS: We used a through scope sphincterotome, which improved the
      ability to traverse difficult strictures. RESULTS: We have used the technique in
      four cases as a last resort. This resulted in a technical success in all four
      cases (100 percent). CONCLUSIONS: Sphincterotome is a useful adjunct in stenting
      difficult colorectal tumor strictures.

PMID- 17216144
TI  - A monosynaptic pathway links the vestibular nuclei and masseter muscle
      motoneurons in rats.
AB  - Physiological evidence indicates that vestibular signals modulate the activity of
      motoneurons innervating the masseter muscle. Recently, experiments using
      transynaptic retrograde transport of pseudorabies virus provided anatomical
      evidence that many neurons concentrated in the dorsomedial part of the
      parvicellular division of the medial vestibular nucleus (MVePC) and the caudal
      prepositus hypoglossi (PH) provide inputs to motoneurons innervating the lower
      third of the superficial layer of the masseter muscle. However, it was not clear
      whether this vestibulo-trigeminal projection was monosynaptic or polysynaptic.
      The present study sought to determine whether neurons in the MVePC or PH project
      directly to motoneurons controlling the masseter muscle in rats. For this
      purpose, an anterograde tracer (biotinylated dextran amine, BDA) was injected
      into vestibular nuclei (mainly MVePC) or PH and a retrograde tracer (the beta
      subunit of cholera toxin, b-CT) was injected into the masseter muscle ipsilateral
      or contralateral to the BDA injection site. Following injections of BDA into the
      vestibular nuclei or PH, anterogradely labeled axon terminals were observed
      bilaterally in the motor trigeminal nucleus (Mo5), particularly in the ventral,
      medial, and lateral portions of the nucleus; projections to dorsal Mo5 were
      sparse. In addition, retrogradely labeled motoneurons were located in the ventral
      and lateral portions of the ipsilateral Mo5. Moreover, anterogradely labeled
      terminals were observed to be in close proximity to motoneurons in the Mo5 that
      were retrogradely labeled from b-CT injections into the masseter muscle. This
      study provides direct evidence that a monosynaptic pathway exists between the
      MVePC and PH and masseter motoneurons.

PMID- 17216145
TI  - A stretch reflex in extraocular muscles of species purportedly lacking muscle
      spindles.
AB  - It is generally assumed that proprioceptive feedback plays a crucial role in limb
      posture and movement. However, the role of afferent signals from extraocular
      muscles (EOM) in the control of eye movement has been a matter of continuous
      debate. These muscles have atypical sensory receptors in several species and it
      has been proposed that they are not supported by stretch reflexes. We recorded
      electromyographic activity of EOM during passive rotations of the eye in sedated
      rats and squirrel monkeys and observed typical stretch reflexes in these muscles.
      Results suggest that there is a similarity in the reflexive control of limb and
      eye movement, despite substantial differences in their biomechanics and sensory
      receptors. Like in some limb skeletal muscles, the stretch reflex in EOM in the
      investigated species might be mediated by other length-sensitive receptors,
      rather than muscle spindles.

PMID- 17216147
TI  - Activity of pursuit neurons in the caudal part of the frontal eye fields during
      static roll-tilt.
AB  - The smooth-pursuit system and vestibular system interact to keep the retinal
      target image on the fovea during head and/or whole body movements. The caudal
      part of the frontal eye fields (FEF) in the fundus of arcuate sulcus contains
      pursuit neurons and the majority of them respond to vestibular stimulation
      induced by whole-body rotation, that activates primarily semi-circular canals,
      and by whole-body translation, that activates otoliths. To examine whether
      coordinate frames representing FEF pursuit signals are orbital or earth-vertical,
      we compared preferred directions during upright and static, whole-body roll-tilt
      in head- and trunk-restrained monkeys. Preferred directions (re monkeys'
      head/trunk axis) of virtually all pursuit neurons tested (n = 21) were similar
      during upright and static whole-body roll-tilt. The slight shift of preferred
      directions of the majority of neurons could be accounted for by ocular counter
      rolling. The mean (+/-SD) differences in preferred directions between upright and
      40 degrees right ear down and between upright and 40 degrees left ear down were 6
      degrees (+/-6 degrees) and 5 degrees (+/-5 degrees), respectively. Visual motion
      preferred directions were also similar in five pursuit neurons tested. To examine
      whether FEF pursuit neurons could signal static whole-body roll-tilt, we compared
      mean discharge rates of 29 neurons during fixation of a stationary spot while
      upright and during static, whole-body roll-tilt. Virtually all neurons tested
      (28/29) did not exhibit a significant difference in mean discharge rates between
      the two conditions. These results suggest that FEF pursuit neurons do not signal
      static roll-tilt and that they code pursuit signals in head/trunk-centered
      coordinates.

PMID- 17216146
TI  - Histone deacetylase inhibitors increase neuronal differentiation in adult
      forebrain precursor cells.
AB  - Chromatin modification plays a key role in fate decision of neural stem cells.
      Here, we explored the impact of epigenetic remodelling onto neuronal fate
      determination using specific inhibitors of histone deacetylases (iHDAC). Adult
      subventricular zone (SVZ) precursor cells were expanded as neurospheres and
      treated in vitro with second generation iHDAC MS-275, M344 and suberoylanilide
      hydroxamic acid (SAHA). All tested compounds revealed a significant increase of
      betaIII-tubulin positive neurons (ranging from 258 to 431%) in a concentration
      dependent manner. The number of oligodendrocytes was decreased by almost 50%,
      accompanied by a reduction of Olig2 mRNA expression. In contrast, astrocyte
      quantity remained unaffected after iHDAC treatment. Both control and iHDAC
      treated cells expressed markers of mature GABAergic and dopaminergic neurons.
      Increased expression levels of NeuroD, Cyclin D2 and B-lymphocyte translocation
      gene 3 (Btg3) point to a shift towards neuronal fate determination targeted by
      HDAC inhibitors.

PMID- 17216148
TI  - Effects of visual stimuli on temporal order judgments of unimanual finger
      stimuli.
AB  - Successive tactile stimuli, delivered one to each hand, are referred to spatial
      representation before they are ordered in time (Yamamoto and Kitazawa in Nat
      Neurosci 4:759-765 2001a). In the present study, we examined if this applies even
      when they are delivered unilaterally to fingers of a single hand. Tactile stimuli
      were delivered left-to-rightward relative to the body (2nd-3rd-4th) or in reverse
      with stimulus onset asynchrony of 100 ms. Simultaneously with the delivery of
      tactile stimuli, three of nine small squares arranged in a matrix of 3 x 3 were
      turned on as if they appeared near the tips of the fingers. Although subjects
      were instructed to ignore the visual stimuli and make a forced choice between the
      two orders of tactile stimuli, the correct-judgment probability depended on the
      direction of visual stimuli. It was greater than 95% when the direction of visual
      stimuli matched that of the tactile stimuli, but less than 50% when they were
      opposite to each other. When the right hand was rotated counterclockwise on the
      horizontal plane (90 degrees ) so that the fingers were pointing to the left, the
      preferred direction of visual stimuli that yielded the peak correct judgment was
      also rotated, although not to the full extent. These results show that subjects
      cannot be basing their tactile temporal order judgment solely on a somatotopic
      map, but rather on a spatial map on which both visual and tactile signals
      converge.

PMID- 17216149
TI  - The three-neuron corneal reflex circuit and modulation of second-order corneal
      responsive neurons.
AB  - Neurons located in the border region between the interpolaris and caudalis
      subdivisions of the spinal trigeminal nucleus (Vi/Vc) are second order neurons of
      the corneal reflex, receiving corneal afferents and projecting to the lid
      closing, orbicularis oculi (OO) motoneurons. Recordings of Vi/Vc neurons
      identified by antidromic activation from stimulation of the facial nucleus and
      non-identified Vi/Vc neurons reveal two neuron types, phasic and tonic. Corneal
      stimulation elicits Adelta latency action potentials that occur early enough to
      initiate OO contraction and C-fiber latency action potentials that can modulate
      the end of the blink in phasic Vi/Vc neurons. Tonic Vi/Vc neurons exhibit a
      constant irregular, low frequency discharge as well as the cornea-evoked activity
      exhibited by phasic neurons. For both phasic and tonic neurons, blink amplitude
      increases with the total number of spikes evoked by the corneal stimulus. Peak
      firing frequency predicts peak orbicularis oculi EMG activity. Paradigms that
      suppress cornea-evoked blinks differentially affect Vi/Vc neurons.
      Microstimulation of the border region between the spinal trigeminal caudalis
      subdivision and the C1 spinal cord (Vc/C1) significantly reduces the number of
      spikes evoked by corneal stimulation and suppresses blink amplitude. In the
      paired stimulus paradigm, a blink evoked by a corneal stimulus 150 ms after an
      identical corneal stimulus is significantly smaller than the blink elicited by
      the first stimulus. Vi/Vc neuron discharge, however, is slightly larger for the
      second blink. Our data indicate that second-order Vi/Vc neurons do not determine
      the specific pattern of OO muscle activity; rather Vi/Vc neurons initiate OO
      motoneuron discharge and program the activity of another circuit that generates
      the late phase of the blink. The Vc/C1 suppression of Vi/Vc neurons suggests that
      the Vc/C1 region provides an "internal model" of the intended blink.

PMID- 17216150
TI  - Lateralized readiness potential elicited by undetected visual stimuli.
AB  - Visual stimuli undetected by normal subjects as a result of masking procedures
      can nonetheless activate response preparation in motor areas and yield a motor
      response. An unanswered question is whether the same holds for undetected
      subliminal stimuli that are not responded to. To answer this question, in this
      study normal subjects were tested on a simple visual reaction time task with
      stimuli above, at, or below the psychophysical threshold while the lateralized
      readiness potential (LRP), i.e. an electrophysiological correlate of premotor
      activation in the primary motor cortex, was computed. We found a reliable LRP not
      only for suprathreshold stimuli but also for subthreshold stimuli to which
      subjects did not respond. The main thrust of this study is that it provides
      evidence that activation of the motor cortex occurs even with subthreshold visual
      stimuli and without an overt response.

PMID- 17216151
TI  - Periodontal anaesthetisation decreases rhythmic synchrony between masseteric
      motor units at the frequency of jaw tremor.
AB  - This study links the reduction in jaw physiological tremor around 8 Hz following
      periodontal mechanoreceptor (PMR) anaesthetisation to changes in coherence
      between masseteric motor unit discharges. We have recorded single motor unit
      activity from two separate sites in the right masseter muscle during a low level
      tonic contraction, both prior to and during anaesthetisation of the peri-incisal
      PMRs. Anaesthetisation of PMRs decreased coherent activity between motor units
      circa 8 Hz, and decreased synchrony between the same motor unit pairs. It is
      proposed that tremor-generating inputs that cause rhythmic synchronisation of
      masseteric motor units arise from, or are amplified by the PMRs.

PMID- 17216152
TI  - Time and decision making: differential contribution of the posterior insular
      cortex and the striatum during a delay discounting task.
AB  - Delay discounting refers to the fact that an immediate reward is valued more than
      the same reward if it occurs some time in the future. To examine the neural
      substrates underlying this process, we studied 13 healthy volunteers who
      repeatedly had to decide between an immediate and parametrically varied delayed
      hypothetical reward using a delay discounting task during event-related
      functional magnetic resonance imaging. Subject's preference judgments resulted in
      different discounting slopes for shorter (<1 year) and for longer (> or =1 year)
      delays. Neural activation associated with the shorter delays relative to the
      longer delays was associated with increased activation in the head of the left
      caudate nucleus and putamen. When individuals selected the delayed relative to
      the immediate reward, a strong activation was found in bilateral posterior
      insular cortex. Several brain areas including the left caudate nucleus showed a
      correlation between the behaviorally determined discounting and brain activation
      for the contrast of intervals with delays <1 and > or =1 year. These results
      suggest that (1) the posterior insula, which is a critical component of the
      decision-making neural network, is involved in delaying gratification and (2) the
      degree of neural activation in the striatum, which plays a fundamental role in
      reward prediction and in time estimation, may code for the time delay.

PMID- 17216153
TI  - Sensory versus motor information in the control of predictive saccade timing.
AB  - Humans readily make predictive saccades to periodic alternating targets. This
      predictive behavior depends on internal monitoring of timing error of past
      saccades in order to determine the time of initiation of future saccades; our
      earlier studies have confirmed this by finding correlations between latencies of
      consecutive predictive saccades. It is natural to consider that timing error is
      determined by visual detection of the difference between the time the target
      appears and the time the eyes arrive at the target; this in turn implies that
      saccades must actually be produced in order for their timing errors to be
      determined and predictive saccade timing to be established. We tested this
      hypothesis by having subjects view alternating visual targets while fixating a
      central target in order to eliminate saccade production. After six alternating
      target presentations, subjects began tracking the alternating targets. Tracking
      performance was assessed with an error measure that compared saccade latency and
      inter-saccade interval with desired values (zero and inter-stimulus interval,
      respectively). Errors in this Prior Viewing paradigm were compared to those from
      a conventional De Novo paradigm in which saccades began as soon as the
      alternating targets were presented. Saccades under Prior Viewing reached a low
      error steady predictive state more rapidly than under De Novo tracking. The
      initial saccade under Prior Viewing had a higher latency than the others,
      suggesting that this saccade was reactive even though the paradigm is
      predictable; other reasons for this higher latency include time to disengage from
      the fixation target and time required to pre-program the initial set of saccades.
      The results show that visual detection of timing error from an actual motor act
      (saccades) is not necessary to establish predictive saccadic pacing: sensory-only
      information from viewing the moving targets can help to establish this predictive
      state.

PMID- 17216154
TI  - Why two "Distractors" are better than one: modeling the effect of non-target
      auditory and tactile stimuli on visual saccadic reaction time.
AB  - Saccadic reaction time (SRT) was measured in a focused attention task with a
      visual target stimulus (LED) and auditory (white noise burst) and tactile
      (vibration applied to palm) stimuli presented as non-targets at five different
      onset times (SOAs) with respect to the target. Mean SRT was reduced (i) when the
      number of non-targets was increased and (ii) when target and non-targets were all
      presented in the same hemifield; (iii) this facilitation first increases and then
      decreases as the time point of presenting the non-targets is shifted from early
      to late relative to the target presentation. These results are consistent with
      the time-window-of-integration (TWIN) model (Colonius and Diederich in J Cogn
      Neurosci 16:1000-1009, 2004) which distinguishes a peripheral stage of
      independent sensory channels racing against each other from a second stage of
      neural integration of the input and preparation of an oculomotor response. Cross
      modal interaction manifests itself in an increase or decrease of second stage
      processing time. For the first time, without making specific distributional
      assumptions on the processing times, TWIN is shown to yield numerical estimates
      for the facilitative effects of the number of non-targets and of the spatial
      configuration of target and non-targets. More generally, the TWIN model framework
      suggests that multisensory integration is a function of unimodal stimulus
      properties, like intensity, in the first stage and of cross-modal stimulus
      properties, like spatial disparity, in the second stage.

PMID- 17216155
TI  - Long-term cocaine self-administration under fixed-ratio and second-order
      schedules in monkeys.
AB  - RATIONALE: Studies in rodents have demonstrated that increased access to cocaine
      can result in increases in drug intake per unit time. OBJECTIVES: The present
      studies characterized long-term changes in cocaine self-administration associated
      with quantitatively and qualitatively different conditions of cocaine
      availability in monkeys. MATERIALS AND METHODS: Separate groups of rhesus monkeys
      (n = 6/group) self-administered cocaine (0.2 mg/kg per injection) under a fixed
      ratio (FR) 30 schedule for 3 h twice daily for two consecutive days each week for
      1 year, or responded under a second-order FR 10 (fixed interval 3-min:S) schedule
      of 0.2 mg/kg per injection cocaine during daily sessions. After 18 weeks, probe
      sessions were conducted once per week, in which responding was maintained under a
      fixed interval (FI) 30-min schedule in the presence of distinct stimuli. RESULTS:
      Weekly cocaine intakes under the FR schedule were stable in three subjects, but
      increased progressively in three monkeys over 1 year. In contrast, response rates
      under the second-order schedule were low and stable over time. Responding under
      the FI 30-min schedule was higher for monkeys in the FR group and pattern of
      responding was not indicative of FI performance, perhaps due to experimental
      history. CONCLUSIONS: These data suggest that increases in cocaine intake can be
      observed under ratio schedules in monkeys. The use of an FI 30-min "probe" to
      assess changes in "drug seeking" appeared to be influenced by experimental
      history. These data may aid in the development of behavioral models of cocaine
      abuse, which focus on the compulsive nature of drug taking.

PMID- 17216156
TI  - Systems-level adaptations explain chronic tolerance development to nitrous oxide
      hypothermia in young and mature rats.
AB  - RATIONALE: Nitrous oxide (N(2)O) can initially lower core temperature (T (core)),
      but hypothermic tolerance develops with chronic administration. Therefore, one or
      both of T (core)'s controlling determinants, heat production (HP) and heat loss
      (HL), must adapt across repeated N(2)O administrations. Simultaneous measurements
      of HP, HL, and T (core) during chronic N(2)O administrations will elucidate this
      adaptive process and constitute a rigorous model for studying the systems-level
      dynamics of tolerance in both mature and young animals. This approach is
      justified by the need to better understand the increased vulnerability to
      addiction associated with adolescent drug use. OBJECTIVES: The objective of the
      study was to measure HL and HP across repeated steady-state administrations of
      60% N(2)O in young and mature rats. MATERIALS AND METHODS: Synchronous
      measurements of HP (indirect calorimetry), HL (direct calorimetry), and T (core)
      (telemetry) were obtained during 60% N(2)O administrations in adolescent (28-45
      days, n = 11) and mature rats (>90 days, n = 8). Rats received five 90-min drug
      exposures (every other day). RESULTS: Compared to mature rats, adolescents
      initially exhibited greater hypothermia, but acquired tolerance more rapidly and
      actually developed hyperthermia during the fifth administration. In both groups,
      N(2)O consistently increased HL, but progressive increases of intrasessional HP
      over repeated administrations prevented hypothermia and subsequently promoted
      hyperthermia in adolescent rats. CONCLUSIONS: Adolescent rats hyper-adapt to
      N(2)O hypothermia. Increases of intrasessional HP across N(2)O administrations
      explained both tolerance to N(2)O hypothermia and the unexpected hyperthermia
      observed in adolescents. These findings raise the possibility that the increased
      vulnerability to addiction associated with adolescent drug use involves a hyper
      adaptive tolerance mechanism.

PMID- 17216157
TI  - Role of test activity in ethanol-induced disruption of place preference
      expression in mice.
AB  - RATIONALE: Reduced expression of a drug-induced conditioned place preference
      (CPP) may reflect a decrease in the drug's conditioned rewarding effects.
      However, CPP is also open to disruption by processes unrelated to the underlying
      motivation. In unpublished studies, we previously observed that ethanol
      pretreatment before testing disrupted expression of ethanol-induced CPP in DBA/2J
      mice. We hypothesized that this interference effect was due to large ethanol
      induced increases in activity. OBJECTIVE: The present studies were designed to
      examine the relationship between test activity and expression of ethanol-induced
      CPP both in the presence and absence of ethanol. To assess the generality of this
      relationship, we examined these effects both in DBA/2J (which are highly
      activated by ethanol) and in NZB/B1NJ mice (which show similar CPP, but less
      ethanol-induced activation). MATERIALS AND METHODS: In separate experiments,
      inbred mice from each strain underwent ethanol (2 g/kg) place conditioning.
      Saline or ethanol was then administered immediately before the test. RESULTS:
      Ethanol, given immediately before the test, blocked the expression of ethanol CPP
      in DBA/2J, but not in NZB/B1NJ mice. Moreover, ethanol significantly increased
      test activity levels in DBA/2J and to a much lesser degree in NZB/B1NJ mice.
      Correlation analyses showed an inverse phenotypic relationship between preference
      and test activity, reflecting stronger preferences in less active mice.
      CONCLUSIONS: Disruption of ethanol-CPP observed in DBA/2J mice may be a
      consequence of high ethanol-induced activity levels. More generally, these
      studies suggest that competing behaviors can affect expression of a drug-induced
      CPP independent of affecting the conditioned rewarding effects of the drug.

PMID- 17216158
TI  - Reliability and uncertainty in the estimation of pKa by least squares nonlinear
      regression analysis of multiwavelength spectrophotometric pH titration data.
AB  - When drugs are poorly soluble then, instead of the potentiometric determination
      of dissociation constants, pH-spectrophotometric titration can be used along with
      nonlinear regression of the absorbance response surface data. Generally,
      regression models are extremely useful for extracting the essential features from
      a multiwavelength set of data. Regression diagnostics represent procedures for
      examining the regression triplet (data, model, method) in order to check (a) the
      data quality for a proposed model; (b) the model quality for a given set of data;
      and (c) that all of the assumptions used for least squares hold. In the
      interactive, PC-assisted diagnosis of data, models and estimation methods, the
      examination of data quality involves the detection of influential points,
      outliers and high leverages, that cause many problems when regression fitting the
      absorbance response hyperplane. All graphically oriented techniques are suitable
      for the rapid estimation of influential points. The reliability of the
      dissociation constants for the acid drug silybin may be proven with goodness-of
      fit tests of the multiwavelength spectrophotometric pH-titration data. The
      uncertainty in the measurement of the pK (a) of a weak acid obtained by the least
      squares nonlinear regression analysis of absorption spectra is calculated. The
      procedure takes into account the drift in pH measurement, the drift in spectral
      measurement, and all of the drifts in analytical operations, as well as the
      relative importance of each source of uncertainty. The most important source of
      uncertainty in the experimental set-up for the example is the uncertainty in the
      pH measurement. The influences of various sources of uncertainty on the accuracy
      and precision are discussed using the example of the mixed dissociation constants
      of silybin, obtained using the SQUAD(84) and SPECFIT/32 regression programs.

PMID- 17216159
TI  - Continuous nondestructive monitoring of Bordetella pertussis biofilms by Fourier
      transform infrared spectroscopy and other corroborative techniques.
AB  - This work describes the application of several analytical techniques to
      characterize the development of Bordetella pertussis biofilms and to examine, in
      particular, the contribution of virulence factors in this development. Growth of
      surface-attached virulent and avirulent B. pertussis strains was monitored in
      continuous-flow chambers by techniques such as the crystal violet method, and
      nondestructive methodologies like fluorescence microscopy and Fourier transform
      (FT) IR spectroscopy. Additionally, B. pertussis virulent and avirulent strains
      expressing green fluorescent protein were grown adhered to the base of a glass
      chamber of 1-microm thickness. Three-dimensional images of mature biofilms,
      acquired by confocal laser scanning microscopy, were quantitatively analysed by
      means of the computer program COMSTAT. Our results indicate that only the
      virulent (Bvg(+)) phase of B. pertussis is able to attach to surfaces and develop
      a mature biofilm. In the virulent phase these bacteria are capable of producing a
      biofilm consisting of microcolonies of approximately 200 microm in diameter and
      24 microm in depth. FTIR spectroscopy allowed us not only to follow the dynamics
      of biofilm growth through specific biomass and biofilm marker absorption bands,
      but also to monitor the maturation of the biofilm by means of the increase of the
      carbohydrate-to-protein ratio.

PMID- 17216161
TI  - Ultrastructural effects of pharmaceuticals (carbamazepine, clofibric acid,
      metoprolol, diclofenac) in rainbow trout (Oncorhynchus mykiss) and common carp
      (Cyprinus carpio).
AB  - In order to assess potential effects of human pharmaceuticals in aquatic
      wildlife, laboratory experiments were conducted with carbamazepine, clofibric
      acid, metoprolol, and diclofenac using fish as test organisms. For each
      substance, at least one environmentally relevant concentration was tested. In
      liver, kidney, and gills of trout and carp exposed to carbamazepine, clofibric
      acid, and metoprolol, ultrastructural effects were qualitatively described and
      semi-quantitatively assessed. The obtained assessment values were compared with
      previously published data for diclofenac-induced effects in rainbow trout
      tissues. Quantitative analyses of protein accumulated in kidneys of diclofenac
      exposed trout corroborated previously published data which indicated that
      diclofenac induced a severe glomerulonephritis resulting in a hyaline droplet
      degeneration of proximal kidney tubules. The investigations provided information
      on the general health status of the pharmaceutical-exposed fish, and allowed a
      differential diagnosis of harmful effects caused by these human pharmaceuticals
      in non-target species. For the different cytological effects observed, lowest
      observed effect concentration (LOECs) for at least three of the test substances
      (diclofenac, carbamazepine, metoprolol) were in the range of environmentally
      relevant concentrations (1 microg/L).

PMID- 17216162
TI  - The efficiency of chemical vapour generation of transition and noble metals.
AB  - The efficiency data from individual reports on chemical vapour generation (CVG)
      of transition and noble metals are overviewed with respect to the ways that they
      were obtained. The values derived from direct measurement of analyte in the
      gaseous phase or obtained from comparison with other sample introduction
      techniques reflect well the true chemical vapour generation efficiency. The
      efficiencies reported this way do not exceed 30%. On the other hand, the
      percentage efficiency values derived from determination of analyte remaining in
      the waste liquid, usually in the high tens, can substantially overestimate the
      efficiency by neglecting the analyte retained within the system.

PMID- 17216164
TI  - Monolayers at solid-solid interfaces probed with infrared spectroscopy.
AB  - The sensitivities of infrared spectra of thin adsorbate layers measured in either
      transmission, internal reflection or external reflection can be greatly increased
      if a light incidence medium with a high refractive index such as an IR
      transparent solid material is used. This increase in sensitivity is due to the
      strong enhancement of the perpendicular electric field in a thin layer of low
      refractive index sandwiched between two high refractive index materials. Based on
      model calculations of a hypothetical sample layer, the influence and optimization
      of experimental parameters such as incidence angle, sample layer thickness and
      optical contact between layers are investigated. Under optimized conditions, this
      enhancement can exceed a factor of 100 when compared to conventional surface IR
      techniques. In addition, the spectra of sandwiched sample layers are governed by
      a uniform surface selection rule, such that only the perpendicular vibrational
      components are enhanced, and they permit a straightforward, substrate-independent
      analysis of surface orientations. Experimental examples of monolayer spectra of
      long-chain hydrocarbon compounds adsorbed onto gold and silicon substrates and
      contacted with a germanium crystal used as the incidence medium demonstrate the
      simple experimental realization and unprecedented sensitivity of this sandwich
      technique, and they offer novel insights into the chemistry and structure of
      monolayers confined and compressed between two solid surfaces.

PMID- 17216165
TI  - Photo-induced cold vapor generation with low molecular weight alcohol, aldehyde,
      or carboxylic acid for atomic fluorescence spectrometric determination of
      mercury.
AB  - With UV irradiation, Hg(2+) in aqueous solution can be converted into Hg(0) cold
      vapor by low molecular weight alcohols, aldehydes, or carboxylic acids, e.g.,
      methanol, formaldehyde, acetaldehyde, glycol, 1,2-propanediol, glycerol, acetic
      acid, oxalic acid, or malonic acid. It was found that the presence of nano-TiO(2)
      more or less improved the efficiency of the photo-induced chemical/cold vapor
      generation (photo-CVG) with most of the organic reductants. The nano-TiO(2)
      enhanced photo-CVG systems can be coupled to various analytical atomic
      spectrometric techniques for the determination of ultratrace mercury. In this
      work, we evaluated the application of this method to the atomic fluorescence
      spectrometric (AFS) determination of mercury in cold vapor mode. Under the
      optimized experimental conditions, the instrumental limits of detection (based on
      three times the standard deviation of 11 measurements of a blank solution) were
      around 0.02-0.04 microg L(-1), with linear dynamic ranges up to 15 microg L(-1).
      The interference of transition metals and the mechanism of the photo-CVG are
      briefly discussed. Real sample analysis using the photo-CVG-AFS method revealed
      that it was promising for water and geological analysis of ultralow levels of
      mercury.

PMID- 17216167
TI  - Denitrification in a binary culture and thiocyanate metabolism in Thiohalophilus
      thiocyanoxidans gen. nov. sp. nov. - a moderately halophilic
      chemolithoautotrophic sulfur-oxidizing Gammaproteobacterium from hypersaline
      lakes.
AB  - Anaerobic enrichment culture with thiocyanate as electron donor and nitrate as
      electron acceptor at 2 M NaCl inoculated with a mixture of sediments from
      hypersaline lakes in Kulunda Steppe (Altai, Russia) resulted in a selection of a
      binary consortium of moderately halophilic, obligately chemolithoautotrophic
      sulfur-oxidizing bacteria (SOB) capable of complete denitrification of nitrate
      with thiosulfate as the electron donor. One consortium member, strain HRhD 3sp,
      was isolated into pure culture with nitrate and thiosulfate using a density
      gradient. This strain was responsible for the reduction of nitrate to nitrite in
      the consortium, while a second strain, HRhD 2, isolated under microoxic
      conditions with thiosulfate as substrate, was capable of anaerobic growth with
      nitrite and thiosulfate. Nitrite, either as substrate or as product, was already
      toxic at very low concentrations for both strains. As a result, optimal growth
      under anaerobic conditions could only be achieved within the consortium. On the
      basis of phylogenetic analysis, both organisms were identified as new lineages
      within the Gammaproteobacteria. As well as thiosulfate, strain HRhD 2 can also
      use thiocyanate as electron donor, representing a first halophilic SOB capable of
      growth with thiocyanate at 2-4 M NaCl. Product and enzymatic analysis identified
      the "carbonyl sulfide (COS) pathway" of primary thiocyanate degradation in this
      new species. On the basis of phenotypic and genetic analysis, strain HRhD 2 is
      proposed to be assigned to a new genus and species Thiohalophilus
      thiocyanoxidans.

PMID- 17216166
TI  - Quantification of left ventricular volumes and ejection fraction from gated 99mTc
      MIBI SPECT: validation of an elastic surface model approach in comparison to
      cardiac magnetic resonance imaging, 4D-MSPECT and QGS.
AB  - PURPOSE: The segmentation algorithm ESM based on an elastic surface model was
      validated for the assessment of left ventricular volumes and ejection fraction
      from ECG-gated myocardial perfusion SPECT. Additionally, it was compared with the
      commercially available quantification packages 4D-MSPECT and QGS. Cardiac MRI was
      used as the reference method. METHODS: SPECT and MRI were performed on 70
      consecutive patients with suspected or proven coronary artery disease. End
      diastolic (EDV) and end-systolic (ESV) volumes and left ventricular ejection
      fraction (LVEF) were derived from SPECT studies by using the segmentation
      algorithms ESM, 4D-MSPECT and QGS and from cardiac MRI. RESULTS: ESM-derived
      values for EDV and ESV correlated well with those from cardiac MRI (correlation
      coefficients R=0.90 and R=0.95, respectively), as did the measurements for LVEF
      (R=0.86). Both EDV and ESV were slightly overestimated for larger ventricles but
      not for smaller ventricles; LVEF was slightly overestimated irrespective of
      ventricle size. The above correlation coefficients are comparable to those for
      the 4D-MSPECT and QGS segmentation algorithms. However, results obtained with the
      three segmentation algorithms are not interchangeable. CONCLUSION: The ESM
      algorithm can be used to assess EDV, ESV and LVEF from gated perfusion SPECT
      images. Overall, the performance was similar to that of 4D-MSPECT and QGS when
      compared with cardiac MRI. Results obtained with the three tested segmentation
      methods are not interchangeable, so that the same algorithm should be used for
      follow-up studies and control subjects.

PMID- 17216169
TI  - Gait assessment in patients with thrust plate prosthesis and intramedullary
      stemmed prosthesis implanted to each hip.
AB  - INTRODUCTION: There has not been any study regarding comparative gait analysis in
      patients with intramedullary stemmed prosthesis (ISP) and thrust plate prosthesis
      (TPP) implanted to each hip. PATIENTS AND METHODS: Four patients (three females
      and one male) who had undergone operation due to coxarthrosis were selected. The
      mean age was 60.5 (37-78) years. TPP and ISP had been implanted to the left and
      right hip, respectively, in three patients, and one patient received TPP to the
      right and ISP to the left hip. Gait was analyzed with a BTS Elite System
      consisting six cameras and two Kistler force plates using Helen Hayes marker set
      to assess the gait parameters. The clinical outcome was also evaluated according
      to Harris hip score (HHS). RESULTS: The average HHS was 95.0 (82-100) points
      after a mean follow-up of 45.0 (30-50) months for TPP and 94.5 (80-100) points
      after a follow-up of 60.0 (14-122) months for ISP. Neither of the HHS scores and
      follow-up time nor gait parameters obtained from the TPP-implanted side were
      statistically different when compared to those of the ISP-implanted side.
      CONCLUSION: TPP and ISP as the implants with their own biomechanical
      specifications did not produce any remarkable difference in gait.

PMID- 17216168
TI  - Kinetics of plasmid transfer among Bacillus cereus group strains within
      lepidopteran larvae.
AB  - The cry toxin encoding plasmid pHT73 was transferred from Bacillus thuringiensis
      subspecies kurstaki KT0 to six B. cereus group strains in three lepidopteran
      (Spodoptera exigua, Plutella xyllostella and Helicoverpa armigera) larvae by
      conjugation. The conjugation kinetics of the plasmid was precisely studied during
      the larval infection using a new protocol. The infections were performed with
      both vegetative and sporulated strains. However, larval death only occurred when
      infections were made with spore and toxin preparations. Likewise, spore
      germinations of both donor and recipient strains were only observed in killed
      larvae, 44-56 h post-infection. Accordingly, kinetics showed that gene transfer
      between B. thuringiensis strain KT0 and other B. cereus strains only took place
      in dead larvae among vegetatively growing bacteria. The conjugational transfer
      ratios varied among different strain combinations and different larvae. The
      highest transfer ratio reached 5.83 x 10(-6) CFU/donor between the KT0 and the
      AW05R recipient in Helicoverpa armigera, and all transconjugants gained the
      ability to produce the insecticidal crystal. These results indicated that
      horizontal gene transfer among B. cereus group strains might play a key role for
      the acquisition of extra plasmids and evolution of these strains in toxin
      susceptible insect larvae.

PMID- 17216170
TI  - Neurovascular complications following percutaneous tendoachillis tenotomy for
      congenital idiopathic clubfoot.

PMID- 17216173
TI  - CT of pregnancy-related complications.
AB  - During pregnancy, the risk of radiation exposure to the fetus is increased so
      that more than the usual benefit is necessary to justify computed tomography (CT;
      or other radiation exposure) than in non-pregnant patients. In the setting of a
      life-threatening illness, CT may be indicated to assess for potentially fatal
      complications such as hemolysis, elevated liver enzymes, and low platelet count
      (HELLP) syndrome. After delivery, patients rarely develop serious problems
      requiring radiologic evaluation. When indicated, however, CT may be invaluable in
      making the diagnosis or determining the severity of peri- and post-partum
      complications, including uterine perforation, hemorrhage, endometritis,
      thrombophlebitis, and abscess formation. At times, CT may be the first to uncover
      conditions, such as post-partum cardiomyopathy, and heart failure, which are
      usually diagnosed by other modalities but may explain the symptoms for which the
      study was ordered. In some centers, CT pulmonary angiography represents the
      standard of care to diagnose pulmonary thromboembolism. In this article, we
      illustrate the spectrum of peri-partum and post-partum complications on CT to
      familiarize the radiologist with the CT features of these potentially life
      threatening pregnancy-related complications.

PMID- 17216171
TI  - Core body temperature regulation of pediatric patients during radiofrequency
      ablation.
AB  - Core body temperature elevation (hyperthermia) can occur during radiofrequency
      ablation of large centrally located tumors in small children. Hyperthermia can be
      predicted on the basis of long burn times, high wattage delivered by the RF
      system and low body weight. If hyperthermia is anticipated, cooling blankets
      using refrigerated air or water are recommended. The advantage of these systems
      is that the cooling can help maintain normal core body temperature.

PMID- 17216174
TI  - Necrotizing fasciitis secondary to diverticulitis.
AB  - Necrotizing fasciitis is a rare, rapidly progressive infectious process primarily
      involving the fascia and the subcutaneous tissue, with thrombosis of the
      cutaneous microcirculation. We present a case of necrotizing fasciitis secondary
      to diverticulitis in an immunosuppressed patient with rheumatoid arthritis.

PMID- 17216172
TI  - Radiation doses to children during modified barium swallow studies.
AB  - BACKGROUND: There are minimal data on radiation doses to infants and children
      undergoing a modified barium swallow (MBS) study. OBJECTIVE: To document
      screening times, dose area product (DAP) and effective doses to children
      undergoing MBS and to determine factors associated with increased screening times
      and effective dose. MATERIALS AND METHODS: Fluoroscopic data (screening time,
      DAP, kVp) for 90 consecutive MBS studies using pulse fluoroscopy were
      prospectively recorded; effective dose was calculated and data were analyzed for
      effects of behavior, number of swallow presentations, swallowing dysfunction and
      medical problems. RESULTS: Mean effective dose for the entire group was 0.0826 +/
      0.0544 mSv, screening time 2.48 +/- 0.81 min, and DAP 28.79 +/- 41.72 cGy cm2.
      Significant differences were found across three age groups (<or=1.0, >1.0-3.0 and
      >3.0 years) for effective dose (mean 0.1188, 0.0651 and 0.0529 mSv, respectively;
      P < 0.001), but not for screening time or DAP. Effective dose was correlated with
      screening time (P = 0.007), DAP (P < 0.001), number of swallow presentations (P =
      0.007), lower age (P = 0.017), female gender (P = 0.004), and height (P < 0.001).
      Screening time was correlated with total number of swallow presentations (P <
      0.001) and DAP (P < 0.001). CONCLUSION: Screening times, DAP, effective dose, and
      child and procedural factors associated with higher effective doses are presented
      for children undergoing MBS studies.

PMID- 17216176
TI  - CT findings in small bowel angioedema: a cause of acute abdominal pain.
AB  - A patient who presented with acute abdominal pain secondary to small bowel
      angioedema is reported. Characteristic imaging features are highlighted with
      clarifying images. The importance of considering this diagnosis in patients
      presenting with acute abdominal pain correlated with the appropriate history is
      discussed.

PMID- 17216175
TI  - Bleeding from peristomal varices in a cirrhotic patient with ileal conduit:
      treatment with transjugular intrahepatic portocaval shunt (TIPS).
AB  - We report an unusual case of a 71-year-old man with liver cirrhosis who presented
      recurred bleedings from the stoma of the ileal conduit after radical
      cystoprostatectomy. The haemorrhages could not be treated by local measures, and
      a transjugular intrahepatic portocaval shunt was performed, displacing an
      endoprosthesis and a self-expandable stent. We highlight the role of TIPS to
      treat recurrent bleedings from the stoma in cirrhotic patients with ileal conduit
      and portal hypertension.

PMID- 17216177
TI  - Diagnosis and treatment of a perforated duodenal diverticulum.
AB  - Perforation is an exceptionally rare complication of duodenal diverticula and
      often presents with nonspecific symptoms and signs. We present a case of a
      perforated duodenal diverticulum diagnosed on computed tomography and
      successfully repaired with a diverticulectomy.

PMID- 17216178
TI  - Yield and utility of radiographic "shunt series" in the evaluation of ventriculo
      peritoneal shunt malfunction in adult emergency patients.
AB  - We examined the yield and utility of shunt series (SS) performed for suspected
      shunt malfunction and whether an abnormal SS lead to shunt revision when head
      computed tomography (CT) was normal or unchanged. We reviewed medical records for
      all adult emergency patients over a 34-month period with suspected shunt
      malfunction imaged with both SS and head CT to determine whether a shunt revision
      was performed contemporaneous with imaging. Nine (3.4%) abnormal SS were
      identified among 263 studies performed. Among the 192 cases in which CT was
      normal or unchanged, two patients with abnormal SS underwent contemporaneous
      shunt revision. Yield of SS is very low, and in the presence of a normal or
      unchanged head CT, SS provides the imaging basis for contemporaneous shunt
      revision in 1% (2/192) of cases.

PMID- 17216179
TI  - Popliteal artery pseudoaneurysm after a revision of total knee arthroplasty:
      endovascular treatment with a stent graft.
AB  - Injury to the popliteal artery during total knee arthroplasty is a very rare but
      dangerous complication. Several mechanisms are capable of generating a direct
      trauma to the vessel, like posterior retractor and oscillating saw. We report a
      case of popliteal artery pseudoaneurysm in a 52-year-old woman that occurred
      during revision of total knee arthroplasty, requiring emergency repair by means
      of percutaneous endovascular covered stenting.

PMID- 17216180
TI  - Reimbursement for chest-pain CT: estimates based on current imaging strategies.
AB  - The purpose of this study was to estimate reimbursement for chest pain CT,
      assuming no cost increase for current emergent chest pain imaging. Using reported
      imaging test characteristics, prevalence and risk of coronary heart disease, and
      Medicare reimbursement schedules, 10,000 simulated patients were evaluated with
      three chest pain imaging algorithms. The main difference among the algorithms was
      the initial imaging tool: stress echocardiography, single photon emission
      computed tomography (SPECT) and chest pain CT. Outcome analysis included deaths,
      intra- and extra-hospital myocardial infraction, number of tests performed, time
      utilization, and the cost per patient. The chest pain CT algorithm was assessed
      with its reimbursement as an unknown to determine a maximum reimbursement that
      would not increase overall healthcare costs. Stress echocardiography costs $856.5
      per patient with 8.4 observation hours and 646 (27%) negative catheterizations.
      When SPECT replaces stress echocardiography, the cost increases to $1,413.7 with
      average observation of 9.05 hours and 1,060 (36%) negative catheterizations.
      Chest pain CT minimizes observation (by 8.4 and 9.1 compared to echocardiography
      and SPECT, respectively); negative catheterizations drop to 266 (12%). Solving
      for chest pain CT reimbursement as an unkown yields $433.1 and $990.3 when
      compared to echocardiography and SPECT, respectively. Under the assumption that
      new technology should not increase overall imaging costs, reimbursement for chest
      pain CT is compatible with current reimbursement for pulmonary embolism and
      aortic dissection CTA. Reimbursements must be weighed against the complexity and
      patient benefits of the examination.

PMID- 17216181
TI  - Tobacco policies in the European Union: a need for state and continental
      harmonisation?

PMID- 17216182
TI  - A juvenile lizard specimen with well-preserved skin impressions from the Upper
      Jurassic/Lower Cretaceous of Daohugou, Inner Mongolia, China.
AB  - Lizards are now relatively well known from the Yixian Formation of northeastern
      China. In this study, we describe a juvenile lizard from a fossil horizon at
      Daohugou, Inner Mongolia. These beds predate the Yixian Formation, and are
      probably Late Jurassic or earliest Cretaceous in age. The new specimen thus
      documents the first lizard material from the Daohugou locality and is the
      earliest lizard skeleton from China. Comparisons with developmental stages of
      modern lizards suggest the Daohugou lizard is a hatchling. Although tiny, the
      specimen is notable in preserving exquisite skin impressions showing the
      variation in scalation across the body, the shape and position of the cloacal
      outlet, and details of the manus and pes. These are the earliest recorded
      lepidosaurian skin traces. In its general proportions and the possession of
      paired frontals, the small Daohugou lizard resembles both the Yixian taxon
      Yabeinosaurus tenuis and the questionable Jeholacerta formosa, but it differs
      from the latter in scalation and, based on other characters, may be distinct from
      both.

PMID- 17216183
TI  - House sparrows benefit from the conservation of white storks.
AB  - As with many farmland bird species, the house sparrow Passer domesticus is
      declining in Europe, mainly due to intensification of agriculture reducing nest
      sites and food supplies. During 2002-2005, we studied the population size and
      nest site characteristics of house sparrows breeding within white stork Ciconia
      ciconia nests in a large area of agricultural landscape within western Poland. To
      explain sparrow density within stork nests, we examined characteristics of white
      stork nests (position, age, productivity) and the farm type around the nest.
      House sparrow density was greatest in the longest established (and hence larger)
      white stork nests located on traditionally managed farms. Two recent changes
      appear to have adverse effects on house sparrows. The first is the
      intensification of farming and the second is active management of white stork
      nests on electric poles to reduce nest size and thus avoid both disruption to the
      electrical supply and electrocution of white storks. Because the white stork has
      such a high profile in Poland, there are numerous schemes to conserve and enhance
      this species. In conclusion, we clearly show that protecting one species can have
      valuable, although unplanned, benefits to another species of conservation
      interest, the house sparrow.

PMID- 17216185
TI  - Population dynamics and regulation in the cave salamander Speleomantes strinatii.
AB  - Time series analysis has been used to evaluate the mechanisms regulating
      population dynamics of mammals and insects, but has been rarely applied to
      amphibian populations. In this study, the influence of endogenous (density
      dependent) and exogenous (density-independent) factors regulating population
      dynamics of the terrestrial plethodontid salamander Speleomantes strinatii was
      analysed by means of time series and multiple regression analyses. During the
      period 1993-2005, S. strinatii population abundance, estimated by a standardised
      temporary removal method, displayed relatively low fluctuations, and the
      autocorrelation function (ACF) analysis showed that the time series had a
      noncyclic structure. The partial rate correlation function (PRCF) indicated that
      a strong first-order negative feedback dominated the endogenous dynamics.
      Stepwise multiple regression analysis showed that the only climatic factor
      influencing population growth rate was the minimum winter temperature. Thus, at
      least during the study period, endogenous, density-dependent negative feedback
      was the main factor affecting the growth rate of the salamander population,
      whereas stochastic environmental variables, such as temperature and rainfall,
      seemed to play a minor role in regulation. These results stress the importance of
      considering both exogenous and endogenous factors when analysing amphibian long
      term population dynamics.

PMID- 17216184
TI  - Power matters in closing the phenotyping gap.
AB  - Much of our understanding of physiology and metabolism is derived from
      investigating mouse mutants and transgenic mice, and open-access platforms for
      standardized mouse phenotyping such as the German Mouse Clinic (GMC) are
      currently viewed as one powerful tool for identifying novel gene-function
      relationships. Phenotyping or phenotypic screening involves the comparison of
      wild-type control mice with their mutant or transgenic littermates. In our study,
      we explored the extent to which standardized phenotyping will succeed in
      detecting biologically relevant phenotypic differences in mice generated and
      provided by different collaborators. We analyzed quantitative metabolic data
      (body mass, energy intake, and energy metabolized) collected at the GMC under the
      current workflow, and used them for statistical power considerations. Our results
      demonstrate that there is substantial variability in these parameters among lines
      of wild-type C57BL/6 (B6) mice from different sources. Given this variable
      background noise in mice that serve as controls, subtle phenotypes in mutant or
      transgenic littermates may be overlooked. Furthermore, a phenotype observed in
      one cohort of a mutant line may not be reproducible (to the same extent) in mice
      coming from a different environment or supplier. In the light of these
      constraints, we encourage researchers to incorporate information on intrastrain
      variability into future study planning, or to perform advanced hierarchical
      analyses. Both will ultimately improve the detectability of novel phenotypes by
      phenotypic screening.

PMID- 17216186
TI  - The evolution of bird migration--a synthesis.
AB  - We approach the problem of the evolution of bird migration by asking whether
      migration evolves towards new breeding areas or towards survival areas in the non
      breeding season. Thus, we avoid the ambiguity of the usually discussed "southern
      home-theory" or "northern-home-theory". We argue that migration evolved in birds
      that spread to seasonal habitats through gradual dispersal to enhance survival
      during the non-breeding season; this in contrast to the alternative idea
      suggesting that migration evolved towards new breeding areas to increase
      reproductive success. Our synthesis is based on the threshold model explaining
      how migratory traits can change rapidly through microevolutionary processes. Our
      model brings former theories together and explains how bird migration, with the
      appropriate direction and time program, evolves through selection after
      genetically non-directed events such as dispersal and colonization. The model
      does not need the former untested assumptions such as competition as a reason for
      migration and for the disappearance of sedentary populations or higher
      reproductive success in temperate breeding areas. Our theory offers answers to
      questions such as how birds with a southern origin may gradually reach northern
      latitudes, why migration routes may follow historical expansion routes and why
      birds leave an area for the non-breeding season and move back instead of breeding
      on their wintering grounds. The theory proposes gradual change through selection
      and not sudden changes such as long distance dispersal or mutations and can be
      applied to migration at all latitudes and in all directions. The scenario
      provides a reasonable concept to understand most of the existing migratory
      phenomena on the basis of the ecology and genetics of migratory behaviour.

PMID- 17216187
TI  - Expression of p53/HGF/c-met/STAT3 signal in fetuses with neural tube defects.
AB  - Neural tube defects (NTD) are morphogenetic alterations due to a defective
      closure of neural tube. Hepatocyte growth factor (HGF)/c-met system plays a role
      in morphogenesis of nervous system, lung, and kidney. HGF/c-met morphogenetic
      effects are mediated by signal transducers and activators of transcription
      (STAT)3 and both HGF and c-met genes are regulated from p53. The aim of our study
      was to analyze mRNA and protein expressions of p53, HGF, c-met, and STAT3 in
      fetuses with NTD. By reverse transcriptase-polymerase chain reaction and
      immunohistochemistry, we analyzed neural tissues from four NTD fetuses and the
      corresponding non-malformed lungs, kidneys and placentas. We found a reduced mRNA
      expression of HGF/c-met/STAT3 pathway, in the malformed nervous systems and
      placentas. The reduced expression of this pathway correlated with the absence of
      p53 in all these samples. On the contrary, detectable expression levels of p53,
      HGF, c-met, and STAT3 were observed in non-malformed lungs and kidneys obtained
      from the same fetuses. Comparable results were obtained by immunohistochemistry,
      with the exception of p53, which was undetected in all fetal tissues. In
      conclusion, in NTD fetuses, both the defective neural tube tissue and the
      placenta have a reduction in all components of the p53/HGF/c-met/STAT3 cascade.
      This raises the possibility of using the suppression of these genes for early
      diagnosis of NTD especially on chorionic villus sampling.

PMID- 17216188
TI  - Hepatocellular carcinoma arising from ectopic liver tissue in the pancreas.
AB  - Liver tissue ectopia is a well-documented phenomenon. Rarely, hepatocellular
      carcinoma arises from the ectopic liver tissue. In this paper, we report a case
      of a primary, well-differentiated hepatocellular carcinoma arising from ectopic
      liver tissue in the pancreas. The patient is a 58-year-old Hispanic man with no
      history of underlying liver diseases or chronic pancreatic diseases. Patient
      presented with a several days history of abdominal pain with radiation to his
      right upper quadrant. Imaging study revealed a 3.7 x 3.3-cm mass in the distal
      pancreas. No other lesions were identified. Preoperative fine needle aspiration
      revealed blood and atypical hepatocytes. The patient underwent distal
      pancreatectomy and splenectomy for suspected neuroendocrine tumor. Gross
      examination revealed a well-circumscribed 3.3-cm, beige-tan, pseudolobulated
      tumor with focal areas of hyperpigmentation. A microscopic examination revealed
      hepatoid cells arranged in a trabecular pattern with focal bile pigment.
      Immunohistochemistry study showed that the tumor cells were reactive with
      hepatocyte antigen (Hep par 1), alpha-1 antitrypsin, but negative for
      synaptophysin and chromogranin. Immunostain for polyclonal carcinoembryonic
      antigen showed a typical bile canalicular pattern. These results support that
      this tumor in the pancreas is hepatocellular carcinoma, most likely arising from
      ectopic liver tissue within the pancreas.

PMID- 17216189
TI  - KiSS-1 overexpression as an independent prognostic marker in hepatocellular
      carcinoma: an immunohistochemical study.
AB  - The KiSS-1 gene has been reported to play an important role as a metastasis
      suppressor gene in various human malignancies. However, there is little
      information about its possible role in hepatocellular carcinoma (HCC). In this
      study, we evaluated the prognostic significance of the expression of KiSS-1 and
      its receptor AXOR12 in 142 HCC tissue specimens by immunohistochemistry. By using
      a cutoff level of 50%, immunoreactivity of KiSS-1 and AXOR12 was found in 6 (4%)
      and 11 (8%) HCCs. The expression of KiSS-1 and AXOR12 in HCC correlated with each
      other (r = 0.42, p < 0.0001) and with the expression in corresponding,
      surrounding liver tissue (both r = 0.35, p < 0.0001). Positive AXOR12
      immunoreactivity in HCC correlated with advanced pT-stage of tumors and low tumor
      grading (r = 0.18, p = 0.032; r = -0.18, p = 0.029). High KiSS-1 expression in
      HCC had a statistically significant influence on diminished disease-free and
      overall survival in uni- (p = 0.006 and p = 0.002) and multivariate analysis (r =
      2.874, p = 0.027 and r = 2.913, p = 0.026). In this study, we report for the
      first time that elevated KiSS-1 expression level in HCC correlates with worsened
      clinical outcome, as an independent prognostic marker for the aggressiveness of
      HCC.

PMID- 17216190
TI  - Taxol-resistance-associated gene-3 (TRAG-3/CSAG2) expression is predictive for
      clinical outcome in ovarian carcinoma patients.
AB  - An obstacle in chemotherapy of ovarian cancer is the development of drug
      resistance. Taxol (paclitaxel)-resistance-associated gene-3 (TRAG-3/CSAG2) was
      found to be overexpressed in a paclitaxel-resistant ovarian carcinoma cell line.
      However, clinical impact of TRAG-3 in ovarian carcinoma has not been demonstrated
      previously. For demonstration of potential clinical impact of TRAG-3,
      immunohistochemistry was applied to determine TRAG-3 protein expression in
      specimens obtained from ovarian carcinoma patients (n=37) who received a
      paclitaxel-based chemotherapy at two different time points, initial laparotomy
      before chemotherapy, and secondary cytoreduction after chemotherapy. The TRAG-3
      specific immunohistochemical staining was correlated with clinical outcome. In
      ovarian carcinoma specimens obtained at the initial laparotomy, an advantage in
      overall (P < 0.001) and progression-free (P = 0.003) survival for patients with
      weak TRAG-3 expression could be demonstrated. Tumor specimens excised at
      secondary cytoreduction procedure were not predictive for clinical outcome. In
      summary, TRAG-3 was found to be a prognostic factor for the prediction of
      clinical outcome after the application of paclitaxel-based chemotherapy.

PMID- 17216191
TI  - Bone marrow as a source of stem cells and germ cells? Perspectives for
      transplantation.
AB  - Recent publications have suggested the existence of germ stem cells in the mouse
      at postnatal stages. The mechanism of de novo oocyte formation is proposed to
      involve a contribution from the bone marrow to the germ cell pool, via the
      bloodstream. Critical examination of the data underpinning these contentious
      claims is under way from a reproductive biology perspective but little has been
      said about the nature of this elusive bone marrow population with germ cell
      potential. Furthermore, whereas the prospect of marrow-derived germ cells may
      appear propitious for fertility applications, its wider impact on transplantation
      medicine remains to be considered. This paper examines the evidence leading to
      the current debate and considers the implications of such findings for the field
      of bone marrow transplantation.

PMID- 17216192
TI  - A proteomic approach to the investigation of early events involved in vascular
      smooth muscle cell activation.
AB  - Vascular smooth muscle cells (VSMC) are mature cells that maintain great
      plasticity. This distinctive feature is the basis of the VSMC migration and
      proliferation involved in cardiovascular diseases. We have used a proteomic
      approach to the molecular changes that promote the switch of VSMC from having a
      quiescent to activated-proliferating phenotype. In particular, we have focused on
      modulations occurring during tyrosine-phosphorylation following cell activation
      by serum or single growth factors, such as insulin-like growth factor 1 or
      platelet-derived growth factor. A comparison of two-dimensional polyacrylamide
      gel profiles from quiescent or activated-proliferating VSMC has allowed us to
      recognize a number of differences in protein expression. Several differentially
      expressed proteins have been identified by mass spectrometry, and their time
      course changes during tyrosine-phosphorylation have been documented from time
      zero till 48 h after stimulation. We have documented a general decrease of the
      tyrosine-phosphorylation level within the first few minutes after stimulation
      followed by a recovery that is quick and dramatic for some chaperones and redox
      enzymes but not so significant for enzymes of glucose metabolism. With regard to
      cytoskeleton components, no remarkable fluctuations have been detected at the
      earliest time points, except for those relative to alpha-actin, which displays an
      impressive decrease. A comparison of the early stages of cell stimulation after
      the administration of serum or single growth factors has brought to light
      important differences in the phosphorylation of chaperones, thereby suggesting
      their crucial role in VSMC activation.

PMID- 17216193
TI  - Passage number affects the pluripotency of mouse embryonic stem cells as judged
      by tetraploid embryo aggregation.
AB  - The aim of this study was to determine whether the number of passages affected
      the developmental pluripotency of embryonic stem (ES) cells as measured by the
      attainment of adult fertile mice derived from embryonic stem (ES) cell/tetraploid
      embryo complementation. Thirty-six newborns were produced by the aggregation of
      tetraploid embryos and hybrid ES cells after various numbers of passages. These
      newborns were entirely derived from ES cells as judged by microsatellite DNA,
      coat-color phenotype, and germline transmission. Although 15 survived to
      adulthood, 17 died of respiratory failure, and four were eaten by their foster
      mother. From the 15 mice that reached adulthood and that could reproduce, none
      arose from ES cells at passage level 15 or more. All 15 arose from cells at
      passages 3-11. Our results demonstrate that the number of passages affects the
      developmental pluripotency of ES cells.

PMID- 17216194
TI  - Immunohistochemical Jun/Fos protein localization and DNA synthesis in rat adrenal
      cortex after treatment with ACTH or FGF2.
AB  - In vitro and in vivo studies have suggested that the expression of the early
      response genes for Jun and Fos proteins plays an important role in adrenal cell
      proliferation. In order to study the expression pattern of the activating protein
      1 (AP-1) family of oncogenes in the adrenal gland, we have used
      immunohistochemistry to localize Jun and Fos protein expression in rat adrenal
      cortex infused in situ with adrenocorticotropic hormone (ACTH), fibroblast growth
      factor 2 (FGF2), or both. The expression of AP-1 factors has been found to be
      correlated with in vivo ACTH and FGF2 proliferation in rats treated with
      dexamethasone and bromodeoxyuridine (BrdU). Induction of c-Jun and c-Fos in the
      zona fasciculata and of FosB in the zona reticularis suggests that, after ACTH
      stimulation, these proteins are the main AP-1 components in these zones. In vivo,
      ACTH increases BrdU-positive cells in the zona fasciculata and zona reticularis
      suggesting that the composition of AP-1 complexes in these zones is correlated
      with proliferation. Patterns of Fos and Jun induction by FGF2 do not resemble
      those after ACTH induction. However, in isolation, neither affects the zona
      glomerulosa. In the zona fasciculata, and more so in the zona reticularis, FGF2
      modulates responses to ACTH, reducing the numbers of Jun-positive cells, Fos
      positive cells, and DNA synthesis. This indicates that FGF2 antagonizes ACTH, and
      that ACTH thus controls the trophic effect independently of exogenous FGF2. Our
      results implicate the AP-1 family of transcription factors in the regulation of
      cell progression and the control of ACTH-induced proliferation in the zona
      fasciculata and zona reticularis.

PMID- 17216195
TI  - Expression of group II metabotropic glutamate receptors in rat gustatory
      papillae.
AB  - Glutamate is one candidate for the neurotransmitters and/or neuromodulators
      involved in taste signaling in taste buds. Group II metabotropic glutamate
      receptors (mGluRs: mGluR2 and mGluR3) are known to function as presynaptic
      receptors that regulate the release of glutamate and/or other neurotransmitters
      in the central nervous system. Group II mGluRs are negatively linked to adenylyl
      cyclase through Galphai subunits and thereby reduce the turnover of cAMP. In rat
      taste tissues, a subset of adenylyl-cyclase-8-expressing taste cells coexpress
      the Galphai subunits gustducin and Galphai2. However, the expression patterns of
      group II mGluRs in rat taste tissues have not yet been elucidated. We have
      therefore examined the expression patterns of mGluR2, mGluR3, and gustducin in
      rat gustatory tissues. Reverse transcription/polymerase chain reaction assays
      have revealed that mGluR2 and mGluR3 mRNAs are expressed in the circumvallate
      papillae. In situ hybridization analyses have detected positive signals for
      mGluR2 and mGluR3 mRNAs only in the circumvallate taste buds. Among the
      fungiform, foliate, and circumvallate papillae, an antibody against mGluR2/3
      labels a subset of taste bud cells and nerve fibers immediately beneath the taste
      lingual epithelium. Double-labeling experiments have demonstrated that mGluR2/3
      positive cells coexpress gustducin. These results indicate that mGluR2 and mGluR3
      are coupled to Galphai subunits and play roles in glutamate-mediated signaling in
      taste transductions.

PMID- 17216196
TI  - Localization of TFF3 peptide in human esophageal submucosal glands and gastric
      cardia: differentiation of two types of gastric pit cells along the rostro-caudal
      axis.
AB  - TFF3 (trefoil factor family 3), which is a major secretory product of the gastric
      antrum and the intestine, but which is nearly absent in the gastric corpus, plays
      a key role in the maintenance of mucosal integrity. Here, we have systematically
      investigated TFF3 expression in the esophagus and gastric cardia by the use of
      reverse transcription/polymerase chain reaction (RT-PCR) analysis and
      immunohistochemistry. Synthesis of TFF3, but not TFF1 or TFF2, is detectable in
      esophageal submucosal glands. The stratified squamous epithelium is devoid of TFF
      synthesis. Prominent TFF3 expression starts at the Z-line with a sharply
      decreasing gradient toward the cardia. Immunohistochemistry has localized TFF3 to
      surface mucous cells of the proximal cardia. TFF3 distribution differs
      characteristically from that of TFF1 (secreted primarily by superficial surface
      mucous cells), whereas TFF3, together with the mucin MUC5AC, is also found in
      deeper lying cells toward the isthmus. This is the first report of TFF3 as a
      typical secretory peptide of esophageal submucosal glands and gastric cardia. The
      different expression patterns of TFF3 and TFF1 in the cardia suggest a stepwise
      maturation of surface mucous cells from TFF3/MUC5AC-positive cells close to the
      isthmus to TFF1/TFF3/MUC5AC-positive cells at the pit. The gradient of TFF3
      expression along the gastric rostro-caudal axis defines two types of gastric pit
      cells: those secreting TFF3 in the cardia and the antrum and those nearly devoid
      of TFF3 synthesis in the corpus. This indicates the special requirement,
      particularly of the esophagogastric junction, for TFF3-triggered protection and
      repair.

PMID- 17216197
TI  - Antimicrobial peptide modulation in a differentiated reconstructed gingival
      epithelium.
AB  - Gingival innate immunity has been studied by using biopsies and normal or
      transformed epithelial cell monolayers. To overcome individual biological
      variabilities and as a physiological alternative, we have proposed using a
      reconstructed tissue equivalent. In this study, we investigated the functionality
      and the stage of differentiation of a reconstructed human gingival epithelium. We
      also characterized this epithelium at the molecular level to investigate its
      differentiation stage compared with native human gingival epithelium. The
      expression levels and localization of markers related to proteins and lipids of
      well-differentiated stratified epithelium, such as cytokeratins, cornified
      envelope proteins and enzymes, or to factors in lipid synthesis and trafficking
      were examined. Immunohistochemistry revealed similar localization patterns in
      both types of epithelia and mRNA quantification showed a close resemblance of
      their expression profiles. We further revealed that, like native gingiva,
      reconstructed gingival epithelium was able to respond to pro-inflammatory or
      lipopolysaccharide stimuli by producing antimicrobial peptides hbetaD-2, hbetaD-3
      or LL-37. Finally, we demonstrated that reconstructed human gingival epithelium,
      as a model, was good enough to be proposed as a functional equivalent for native
      human gingival epithelium in order to study the regulation of gingival innate
      immunity against periodontal infections.

PMID- 17216198
TI  - Comparative characterization of pulmonary surfactant aggregates and alkaline
      phosphatase isozymes in human lung carcinoma tissue.
AB  - Alkaline phosphatase (AP) isozymes are surfactant-associated proteins (SPs).
      Since several different AP isozymes have been detected in the pneumocytes of lung
      cancer patients, we attempted to identify the relationship between pulmonary
      surfactant aggregate subtypes and AP isozymes. Pulmonary surfactant aggregates
      were isolated from carcinoma and non-carcinoma tissues of patients with non-small
      cell carcinoma of the lung. Upon analysis, ultraheavy, heavy, and light
      surfactant aggregates were detected in the non-carcinoma tissues, but no
      ultraheavy surfactant aggregates were found in the carcinoma tissues. Surfactant
      associated protein A (SP-A) was detected as two bands (a 27-kDa band and a 54-kDa
      band) in the ultraheavy, heavy, and light surfactant aggregates found in the non
      carcinoma tissues. Although both SP-A bands were detected in the heavy and light
      surfactant aggregates from adenocarcinoma tissues, the 54-kDa band was not
      detected in squamous cell carcinoma tissues. Liver AP (LAP) was detected in the
      heavy and light surfactant aggregates from both non-carcinoma and squamous
      carcinoma tissues, but not in heavy surfactant aggregates from adenocarcinoma
      tissues. A larger amount of bone type AP (BAP) was found in light surfactant
      aggregate fractions from squamous cell carcinomas than those from adenocarcinoma
      tissues or non-carcinoma tissues from patients with either type of cancer. LAP,
      BAP, and SP-A were identified immunohistochemically in type II pneumocytes from
      non-carcinoma tissues and adenocarcinoma cells, but no distinct SP-A staining was
      observed in squamous cell carcinoma tissues. The present study has thus revealed
      several differences in pulmonary surfactant aggregates and AP isozymes between
      adenocarcinoma tissue and squamous cell carcinoma tissue.

PMID- 17216199
TI  - Localization of leucomyosuppressin in the brain and circadian clock of the
      cockroach Leucophaea maderae.
AB  - The myosuppressins (X1DVX2HX3FLRFamide), which reduce the frequency of insect
      muscle contractions, constitute a subgroup of the FMRFamide-related peptides. In
      the cockroach Leucophaea maderae, we have examined whether leucomyosuppressin
      (pQDVDHVFLRFamide) is present in the accessory medulla, viz., the circadian
      clock, which governs circadian locomotor activity rhythms. Antisera that
      specifically recognize leucomyosuppressin stain one to three neurons near the
      accessory medulla. MALDI-TOF mass spectrometry has confirmed the presence of
      leucomyosuppressin in the isolated accessory medulla. Injections of 1.15 pmol
      leucomyosuppressin into the vicinity of the accessory medulla at various
      circadian times have revealed no statistically significant effects on the phase
      of circadian locomotor activity rhythms. This is consistent with the morphology
      of the myosuppressin-immunoreactive neurons, which restrict their arborizations
      to the circadian clock and other optic lobe neuropils. Thus, leucomyosuppressin
      might play a role in the circadian system other than in the control of locomotor
      activity rhythms.

PMID- 17216200
TI  - Sequential expression of endothelial nitric oxide synthase, inducible nitric
      oxide synthase, and nitrotyrosine in odontoblasts and pulp cells during dentin
      repair after tooth preparation in rat molars.
AB  - Nitric oxide (NO) stimulates osteoblast differentiation, but whether NO
      contributes to odontoblast differentiation during dentin repair is unknown. By
      using reverse transcription/polymerase chain reaction and immunostaining, we
      investigated the gene expression and/or immunolocalization of endothelial NO
      synthase (eNOS), inducible NOS (iNOS), and nitrotyrosine (a biomarker for NO
      derived peroxinitrite), and alkaline phosphatase (ALP) and osteocalcin (early and
      terminal differentiation markers of odontoblasts, respectively) in dental pulp
      tissue after rat tooth preparation. At the early stage (1-3 days) post
      preparation, markedly increased expression of iNOS and nitrotyrosine was found in
      odontoblasts and pulp cells beneath the cavity, whereas eNOS expression was
      significantly decreased. ALP mRNA expression was significantly increased after 1
      day but decreased after 3 days, whereas ALP activity was weak in the dentin-pulp
      interface under the cavity after 1 day but strong after 3 days. Osteocalcin mRNA
      expression was significantly increased at this stage. At 7 days post-preparation,
      tertiary dentin was formed under the cavity. All the molecules studied were
      expressed at control levels in odontoblasts/pulp cells beneath the cavity. These
      findings show that abundant NO is released from odontoblasts and pulp cells at an
      early stage after tooth preparation and indicate that, after tooth preparation,
      the up-regulation of iNOS and nitrotyrosine in odontoblasts is synchronized with
      increased cellular expression of ALP and osteocalcin. Therefore, the NO
      synthesized by iNOS after tooth preparation probably participates in regulating
      odontoblast differentiation during tertiary dentinogenesis.

PMID- 17216201
TI  - Factors related to anxiety and depression in women with breast cancer and their
      husbands: role of alexithymia and family functioning.
AB  - GOALS OF WORK: The purpose of this study was to explore alexithymia, family
      functioning, and other factors that might affect anxiety and depression levels in
      women with breast cancer and in their husbands. PATIENTS AND METHODS: A cross
      sectional study was undertaken in 46 postsurgical ambulatory women with breast
      cancer and their husbands. Documented informed consent for the study was obtained
      from each subject. All subjects completed the Zung self-rating anxiety scale
      (SAS), the Zung self-rating depression scale (SDS), the 20-item Toronto
      alexithymia scale (TAS-20), and the family assessment device (FAD). MAIN RESULTS:
      Multiple regression analysis revealed that a high degree of alexithymia in
      patients correlated with a high degree of patient anxiety. Patient perceptions of
      inappropriate affective responsiveness among family members correlated with a
      high degree of depression. Among husbands, a high degree of anxiety was
      correlated with their own high level of alexithymia or low level of education,
      and with the occurrence of adjuvant therapy in their wives. Husband perceptions
      of inappropriate sharing of roles among family members, their own low education
      level, and a large number of family members correlated with high degrees of
      depression among them. CONCLUSIONS: The present study revealed that alexithymia
      and family functioning are associated with anxiety and depression, respectively,
      in both women with breast cancer and in their husbands. Individual traits such as
      alexithymia and family functioning should be taken into account when we intervene
      to treat anxiety and depression in breast cancer patients and their husbands.

PMID- 17216202
TI  - The role of STATs in lung carcinogenesis: an emerging target for novel
      therapeutics.
AB  - The signal transducer and activator of transcription (STAT) proteins are a family
      of latent cytoplasmic transcription factors, which form dimers when activated by
      cytokine receptors, tyrosine kinase growth factor receptors as well as non
      receptor tyrosine kinases. Dimeric STATs translocate to the nucleus, where they
      bind to specific DNA-response elements in the promoters of target genes, thereby
      inducing unique gene expression programs often in association with other
      transcription regulatory proteins. The functional consequence of different STAT
      proteins activation varies, as their target genes play diverse roles in normal
      cellular/tissue functions, including growth, apoptosis, differentiation and
      angiogenesis. Certain activated STATs have been implicated in human
      carcinogenesis, albeit only few studies have focused into their role in lung
      tumours. Converging evidence unravels their molecular interplays and complex
      multipartite regulation, rendering some of them appealing targets for lung cancer
      treatment with new developing strategies.

PMID- 17216203
TI  - Renalase gene is a novel susceptibility gene for essential hypertension: a two
      stage association study in northern Han Chinese population.
AB  - Renalase, a novel flavin adenine dinucleotide-dependent amine oxidase, is
      secreted by the kidney, degrades circulating catecholamines, and modulates
      cardiac function and systemic blood pressure (BP). Its discovery may provide
      novel insights into the mechanisms of BP regulation and the pathogenesis of
      essential hypertension (EH). We designed a two-stage case-control study to
      investigate whether the renalase gene harbored any genetic variants associated
      with EH in the northern Han Chinese population. From the International
      Collaborative Study of Cardiovascular Disease in Asia (InterASIA in China), 1,317
      hypertensive cases and 1,269 normotensive controls were recruited. These total
      2,586 subjects were taken as the main study population in this study. In stage 1,
      all the eight selected single nucleotide polymorphisms (SNPs) of the renalase
      gene were genotyped and tested within a subsample (503 cases and 490 controls) of
      the main study population. By single locus analyses, three SNPs, rs2576178,
      rs2296545, and rs2114406, showed significant associations with EH (P < 0.05). In
      stage 2, these three SNPs were genotyped on the remaining individuals and
      analyzed using all the individuals. After Bonferroni correction for multiple
      comparisons, the associations of rs2576178 and rs2296545 with EH were still
      significant in stage 2. The cases had higher frequencies of rs2576178 G allele
      and rs2296545 C allele than the controls (0.55 versus 0.49, P < 0.0001; 0.61
      versus 0.55, P < 0.0001). Particularly, under the codominant model, the adjusted
      odds ratios for rs2576178 GG genotype and rs2296545 CC genotype were 1.58 (95%
      CI, 1.25 to 2.00; P = 0.0002) and 1.61 (95% CI, 1.26 to 2.04; P = 0.0002),
      respectively. We also found risk-associated haplotypes and diplotypes, which
      further confirmed the significant association between the renalase gene and EH.
      These findings may provide novel genetic susceptibility markers for EH and lead
      to a better understanding of EH pathophysiology. In addition, further
      replications in other populations and functional studies would be warranted.

PMID- 17216205
TI  - Activation of soluble guanylate cyclase by nitric oxide in lymphocytes correlates
      with minimal hepatic encephalopathy in cirrhotic patients.
AB  - Patients with liver cirrhosis with normal neurological and mental status
      examination may present minimal forms of hepatic encephalopathy, showing
      intellectual function impairment that cannot be detected through general clinical
      examination but can be unveiled using specific neuropsychological or
      neurophysiological examination. Evaluation of minimal hepatic encephalopathy
      (MHE) in cirrhotic patients would have prognostic value. The psychometric hepatic
      encephalopathy score (PHES) has been recommended as the "gold standard" in the
      diagnosis of MHE. Altered modulation of cyclic GMP (cGMP) levels in the brain
      seems to be responsible for the impairment of some types of cognitive function in
      liver disease. In animal models of liver disease, some of the alterations in
      modulation of cGMP levels in the brain are reproduced in lymphocytes. The aim of
      the present work was to assess whether there is a correlation between the
      alterations in different parameters involved in modulation of cGMP levels and the
      presence of MHE in patients with liver disease. We studied in 46 patients with
      liver cirrhosis and 26 controls the performance in the PHES battery of
      psychometric tests and the critical flicker frequency (CFF), the concentration of
      cGMP in plasma and lymphocytes, activation of guanylate cyclase by nitric oxide
      (NO) in lymphocytes, and several parameters likely involved in altered cGMP
      homeostasis in liver disease such as ammonia, NO metabolites, and atrial
      natriuretic peptide (ANP). Activation of guanylate cyclase by NO in lymphocytes
      and cGMP in plasma were higher and CFF lower in patients with MHE than in
      patients without MHE. Ammonia, ANP, and metabolites of NO were higher in patients
      than in controls but were no different in patients with or without MHE.
      Alteration in activation of guanylate cyclase by NO in lymphocytes correlates
      with PHES performance, CFF, and ammonia levels. This suggests that altered
      modulation of guanylate cyclase by NO in lymphocytes would reflect a parallel
      alteration in the brain occurring in patients with MHE that would be involved in
      their cognitive impairment.

PMID- 17216204
TI  - The unfolded protein response and cancer: a brighter future unfolding?
AB  - Mammalian cells are bathed in an interstitial fluid that has a tightly regulated
      composition in healthy states. Interstitial fluid provides cells with all the
      necessary metabolic substrates (oxygen, glucose, amino acids, etc.), and waste
      molecules are removed by diffusion gradients that are controlled by local
      vascular perfusion. The health and normal function of all cells within a body is
      dependent on the maintenance of this microenvironment. However, many disease
      states cause fluctuations in this, and in some instances, these might be of
      sufficient severity to stress and/or be toxic to the cell. Cells have developed a
      number of responses to enable their survival in a hostile environment. This
      article discusses one such pathway--the unfolded protein response and its
      relationship to cancer. The molecular signalling cascade, the mechanism of its
      activation in cancer and the consequences of its activation for a tumour are
      discussed, as are clinical studies and potential translational approaches for
      utilising this pathway for tumour targeting.

PMID- 17216208
TI  - The functional Pro129Thr variant of the FAAH gene is not associated with various
      fat accumulation phenotypes in a population-based cohort of 5,801 whites.
AB  - Food intake and weight gain are influenced by endocannabinoids whose actions are
      regulated by the fatty acid amide hydrolase (FAAH) enzyme. The homozygous Thr/Thr
      genotype of the functional Pro129Thr variant (rs324420) in the gene encoding FAAH
      was recently reported to associate with overweight and obesity in white and black
      populations. We investigated the Pro129Thr variant in relation to overweight and
      obesity in a relatively large population-based study sample of Danish whites
      (n=5,801). In case-control studies of obesity, a borderline association with the
      major Pro allele was identified; however, after correction for multiple testing,
      no association was found. Furthermore, a possible association between the major
      Pro allele and obesity was not supported by studies of obesity-related
      quantitative traits. In conclusion, in a large study sample, we were unable to
      find robust evidence of an association of the Pro129Thr FAAH variant with
      overweight, obesity, and any related quantitative traits among the examined
      whites.

PMID- 17216209
TI  - Bryophyte dispersal by flying foxes: a novel discovery.
AB  - This research provides the first evidence of dispersal of bryophytes and
      associated microorganisms through ingestion by a highly mobile vertebrate vector,
      the spectacled flying fox (Pteropus conspicillatus). Bryophyte fragments were
      found in faeces collected at four P. conspicillatus' camps in the Wet Tropics
      bioregion, northeastern Australia. These fragments were viable when grown in
      culture; live invertebrates and other organisms were also present. Our study has
      significantly increased understanding of the role of flying foxes as dispersal
      vectors in tropical forests.

PMID- 17216207
TI  - A quantitative real-time immuno-PCR approach for detection of staphylococcal
      enterotoxins.
AB  - Bacterial intoxications represent a substantial public health concern with
      enterotoxins produced by Staphylococcus aureus among the most common causes of
      food poisoning. In addition to their role in the pathogenicity of food poisoning,
      staphylococcal enterotoxins have profound effects on the immune system as members
      of the family of pyrogenic toxin superantigens. As the classical diagnostic
      bioassays as well as the routinely used immunological methods are hampered by
      several drawbacks regarding sensitivity, specificity, and practicability, there
      is a need for the timely identification of toxins by highly sensitive and
      specific methods. To combine the versatility of an enzyme immunoassay (EIA) with
      the amplification power of the PCR, a quantitative real-time immuno-PCR (qRT
      iPCR) was developed for the detection of staphylococcal enterotoxins A and B and
      compared to a commercially available EIA. A broadly applicable tool for signal
      amplification of pre-formed immunocomplexes was established by covalent binding
      of a reporter DNA to secondary detection antibodies. Therefore, the amino
      modified reporter DNA was coupled successfully to N-succinimidyl-S-actyl
      thioacetate-activated secondary detection antibodies. The qRT-iPCR was able to
      detect highly reproducibly as low as approximately 0.6 to 6 pg (4 to 40
      amol/microl) of staphylococcal enterotoxin B and staphylococcal enterotoxin A,
      respectively. In conclusion, the qRT-iPCR approach was shown to overcome clearly
      the sensitivity limit of traditional immunological detection procedures for
      bacterial toxins, as demonstrated in this study for staphylococcal enterotoxins.
      The development of a stable antibody-DNA conjugate providing a universal signal
      amplification offers a versatile as well as a highly sensitive and specific tool
      for diagnostic and research purposes generally applicable for pre-formed antibody
      antigen complexes.

PMID- 17216210
TI  - The predatory behavior of wintering Accipiter hawks: temporal patterns in
      activity of predators and prey.
AB  - Studies focused on how prey trade-off predation and starvation risk are prevalent
      in behavioral ecology. However, our current understanding of these trade-offs is
      limited in one key respect: we know little about the behavior of predators. In
      this study, we provide some of the first detailed information on temporal
      patterns in the daily hunting behavior of bird-eating Accipiter hawks and relate
      that to their prey. During the winters of 1999-2004, twenty-one sharp-shinned
      hawks (A. striatus) and ten Cooper's hawks (A. cooperii) were intensively radio
      tracked in rural and urban habitats in western Indiana, USA. Cooper's hawks left
      roost before sunrise and usually returned to roost around sunset, while sharp
      shinned hawks left roost at sunrise or later and returned to roost well before
      sunset. An overall measure of Cooper's-hawk-induced risk (a composite variable of
      attack rate and activity patterns) generally reflected the timing of prey
      activity, with peaks occurring around sunrise and sunset. In contrast, risk
      induced by the smaller sharp-shinned hawk did not strongly reflect the activity
      of their prey. Specifically, an early morning peak in prey activity did not
      correspond to a period with intense hawk activity. The lack of early morning
      hunting by sharp-shinned hawks may reflect the high risk of owl-induced predation
      experienced by these hawks. The net effect of this intraguild predation may be to
      "free" small birds from much hawk-induced predation risk prior to sunrise. This
      realization presents an alternative to energetics as an explanation for the early
      morning peak in small bird activity during the winter.

PMID- 17216206
TI  - Multifunctional antimicrobial peptides: therapeutic targets in several human
      diseases.
AB  - Antimicrobial peptides have emerged as promising agents against antibiotic
      resistant pathogens. They represent essential components of the innate immunity
      and permit humans to resist infection by microbes. These gene-encoded peptides
      are found mainly in phagocytes and epithelial cells, showing a direct activity
      against a wide range of microorganisms. Their role has now broadened from that of
      simply endogenous antibiotics to multifunctional mediators, and their
      antimicrobial activity is probably not the only primary function. Although
      antimicrobial peptide deficiency, dysregulation, or overproduction is not known
      to be a direct cause of any single human disease, numerous studies have now
      provided compelling evidence for their involvement in the complex network of
      immune responses and inflammatory diseases, thereby influencing diverse processes
      including cytokine release, chemotaxis, angiogenesis, wound repair, and adaptive
      immune induction. The purpose of this review is to highlight recent literature,
      showing that antimicrobial peptides are associated with several human conditions
      including infectious and inflammatory diseases, and to discuss current clinical
      development of peptide-based therapeutics for future use.

PMID- 17216211
TI  - Phenotypically plastic responses of green frog embryos to conflicting predation
      risk.
AB  - Predators have been shown to alter the timing of switch points between life
      history stages, but few studies have addressed switch point plasticity in prey
      exposed simultaneously to conflicting predation pressure. We tested hatching
      responses of green frog (Rana clamitans) embryos subject to perceived predation
      risk from chemical cues released by two stage-specific predators, predicting that
      these predators would elicit: (1) directional hatching responses when presented
      independently, and (2) intermediate phenotypic responses when presented
      simultaneously. R. clamitans embryos in outdoor exclosures were exposed to cues
      from an egg predator (freshwater leeches; Nephelopsis obscura), a larval predator
      (dragonfly nymphs, Aeschna canadensis), and both predators in a 2 x 2 factorial
      experiment, and changes in hatchling size, hatchling developmental stage, and
      hatching time were compared to those for control embryos. Leeches alone induced
      embryos to hatch at a smaller size and an earlier developmental stage than
      controls, while dragonfly nymphs elicited a delay in egg hatching time that was
      associated with larger size and later developmental stage at hatching. Embryos
      failed to respond to simultaneous exposure to both predators, implying that
      responses to each occurred concurrently and were therefore dampened. Our results
      indicate that prey under threat from conflicting predators may manifest
      intermediate defensive phenotypes. Such intermediate responses may result in
      elevated rates of prey mortality with possible consequences at the population
      level.

PMID- 17216212
TI  - Do metal-rich plants deter herbivores? A field test of the defence hypothesis.
AB  - Some plant species growing on metalliferous soils are able to accumulate heavy
      metals in their shoots up to very high concentrations, but the selective
      advantage of this behaviour is still unknown. The most popular hypothesis, that
      metals protect plants against herbivores, has been tested several times in
      laboratory conditions, with contradictory results. We carried out the first large
      scale test of the defence hypothesis in eight natural populations of the model Zn
      hyperaccumulator Thlaspi caerulescens J. and C. Presl (Brassicaceae). In two
      climatic regions (temperate, Belgium-Luxembourg, and Mediterranean, southern
      France), we worked in metalliferous and in normal, uncontaminated environments,
      with plants spanning a wide range of Zn concentrations. We also examined the
      importance of glucosinolates (main secondary metabolites of Brassicaceae) as
      antiherbivore defences. When exposed to natural herbivore populations, T.
      caerulescens suffered lower herbivory pressures in metal-enriched soils than in
      normal soils, both in Belgium-Luxembourg and in southern France. The trapping of
      gastropods shows an overall lower population density in metalliferous compared to
      normal environments, which suggests that herbivory pressure from gastropods is
      lower on metalliferous soils. In addition, foliar concentration of glucosinolates
      was constitutively lower in all populations from metal-enriched soils, suggesting
      that these have evolved towards lower investment in organic defences in response
      to lower herbivory pressure. The Zn concentration of plants had a protective role
      only for Belgian metallicolous plants when transplanted in normal soils of
      Luxembourg. These results do not support the hypothesis that Zn plays a key role
      in the protection of T. caerulescens against enemies. In contrast, glucosinolates
      appear to be directly involved in the defence of this hyperaccumulator against
      herbivores.

PMID- 17216213
TI  - Water source partitioning among trees growing on shallow karst soils in a
      seasonally dry tropical climate.
AB  - The sources of water used by woody vegetation growing on karst soils in
      seasonally dry tropical regions are little known. In northern Yucatan (Mexico),
      trees withstand 4-6 months of annual drought in spite of the small water storage
      capacity of the shallow karst soil. We hypothesized that adult evergreen trees in
      Yucatan tap the aquifer for a reliable supply of water during the prolonged dry
      season. The naturally occurring concentration gradients in oxygen and hydrogen
      stable isotopes in soil, bedrock, groundwater and plant stem water were used to
      determine the sources of water used by native evergreen and drought-deciduous
      tree species. While the trees studied grew over a permanent water table (9-20 m
      depth), pit excavation showed that roots were largely restricted to the upper 2 m
      of the soil/bedrock profile. At the peak of the dry season, the delta(18)O
      signatures of potential water sources for the vegetation ranged from 4.1 +/- 1.1
      per thousand in topsoil to -4.3 +/- 0.1 per thousand in groundwater. The
      delta(18)O values of tree stem water ranged from -2.8 +/- 0.3 per thousand in
      Talisia olivaeformis to 0.8 +/- 1 per thousand in Ficus cotinifolia,
      demonstrating vertical partitioning of soil/bedrock water among tree species.
      Stem water delta(18)O values were significantly different from that of
      groundwater for all the tree species investigated. Stem water samples plotted to
      the right of the meteoric water line, indicating utilization of water sources
      subject to evaporative isotopic enrichment. Foliar delta(13)C in adult trees
      varied widely among species, ranging from -25.3 +/- 0.3 per thousand in
      Enterolobium cyclocarpum to -28.7 +/- 0.4 per thousand in T. olivaeformis.
      Contrary to initial expectations, data indicate that native trees growing on
      shallow karst soils in northern Yucatan use little or no groundwater and depend
      mostly on water stored within the upper 2-3 m of the soil/bedrock profile. Water
      storage in subsurface soil-filled cavities and in the porous limestone bedrock is
      apparently sufficient to sustain adult evergreen trees throughout the pronounced
      dry season.

PMID- 17216214
TI  - Biotic constraints on the invasion of diffuse knapweed (Centaurea diffusa) in
      North American grasslands.
AB  - Knapweeds (Centaurea spp.) are among the most invasive of non-indigenous plant
      species that have colonized western North America over the last century. We
      conducted a 4-year experiment in a reconstructed grassland to test hypotheses
      related to the ability of grasslands to resist the invasion of diffuse knapweed
      (C. diffusa). We experimentally invaded C. diffusa and three native species into
      areas where we manipulated soil nitrogen (N) and phosphorus (P) availability and
      removed extant grasses to reduce competition. We evaluated the growth response of
      these species to these resources and competitive manipulations. Of the native
      species that were experimentally added, only one species, Ratibida pinnata
      (prairie coneflower), established in any numbers. Establishment values in intact
      vegetation were low for both species, but establishment by C. diffusa (0.02%)
      clearly outperformed that of R. pinnata (0.001%). Under reduced grass
      competition, establishment was enhanced, but the values for C. diffusa (0.68%)
      were not statistically different from those of R. pinnata (0.57%). Neither
      species performed better under higher soil nutrients in the presence of competing
      grasses. In plots with both species, biomass of the two planted species was
      positively correlated, but the biomass of both species was negatively correlated
      with non-added weedy species. Subsequent harvests of C. diffusa indicated that
      establishment was enhanced in treatments with higher soil nutrients but that the
      biomass of these plants could only be enhanced when plant competition was also
      reduced. These results indicate that C. diffusa can establish in intact
      grasslands at rates higher than natives, but opportunism rather than competitive
      ability best describes the invasiveness of C. diffusa. Thus, the mechanisms
      contributing to the establishment of this knapweed species are different from
      factors identified as contributing to the dominance of this invader.

PMID- 17216215
TI  - Maternal androgens in the pied flycatcher: timing of breeding and within-female
      consistency.
AB  - Maternal hormones can have substantial phenotypic effects in the progeny of many
      vertebrates. It has been proposed that mothers adaptively adjust hormone levels
      experienced by particular young to optimize their reproductive output. In birds,
      systematic variation in egg hormone levels has been related to different female
      reproductive strategies. Because in many bird species prospects of the offspring
      change seasonally and with brood number, strategic adjustment of yolk androgen
      levels would be expected. To test this idea, we induced pied flycatcher (Ficedula
      hypoleuca) females to nest twice during the same season by removing their first
      clutches shortly after clutch completion. We collected eggs of first and
      replacement clutches to measure yolk concentrations of androstenedione (A4) and
      testosterone (T) and captured the females that laid these clutches for phenotypic
      measurements. Although average egg androgen levels were remarkably consistent
      within females, hormone patterns differed considerably between first and
      replacement clutches. Eggs of replacement clutches were heavier with larger yolks
      compared to first clutches, but they contained on average lower levels of
      androgens. Within clutches, androgen concentration increased over the laying
      sequence in the first clutch, but decreased or remained more constant over the
      laying sequence in the replacement clutch. Mean yolk T, but not A4 levels, were
      negatively associated with laying date for both breeding attempts. Moreover,
      females in good body condition produced eggs containing lower levels of androgens
      than females in poor condition. Our results are consistent with the idea that
      differences in yolk androgen levels may be one mechanism underlying seasonal
      variation in reproductive success and it is possible that changes in egg androgen
      patterns may reflect a change in female reproductive strategy. High within-female
      consistency also highlights the possibility that there may be some underlying
      genetic variation in yolk androgen levels.

PMID- 17216216
TI  - Cutaneous larva migrans in northern Germany.
AB  - We report a 14-month-old female infant with typical cutaneous larva migrans, but
      without a history of travelling outside Germany. Cutaneous larva migrans is most
      commonly observed in and imported from tropical countries. Only a few cases have
      been described in northern Europe. This report serves as a reminder that under
      certain circumstances acquisition of this "tropical" parasite is possible even in
      non-tropical countries.

PMID- 17216217
TI  - Endosonographic and manometric evaluation of internal anal sphincter in patients
      with chronic anal fissure and its correlation with clinical outcome after topical
      glyceryl trinitrate therapy.
AB  - BACKGROUND AND AIMS: Anorectal pressure studies have demonstrated internal anal
      sphincter (IAS) hypertonia in patients with chronic anal fissure. It is unknown
      however, if these changes in IAS function are associated with any abnormality in
      sphincter morphology. The first aim was to investigate the clinical
      characteristics and the manometric and endosonographic findings of the IAS in a
      cohort of patients with chronic anal fissure. The second aim was to investigate
      the association between these findings and the outcome with topical Glyceryl
      trinitrate (GTN) therapy. MATERIALS AND METHODS: All patients who presented with
      chronic anal fissure from November 1999 to May 2004 were included after failure
      of conservative therapy. Anorectal manometry and anal endosonography were
      performed before treatment with 0.2% GTN ointment twice daily was initiated.
      Patients were evaluated after 8 weeks. RESULTS: One hundred and twenty-four
      patients (66 women, mean age, 45.2 +/- 14.8 years) were included. Hypertonia of
      the IAS was found in 84 (68%) patients. The mean maximum IAS thickness was 3.6 +/
      0.76 mm (1.6-5.5). An abnormally thick IAS, adjusted by age, was observed in 113
      (91.1%) patients. We found no correlation between resting pressure and IAS
      thickness (r = 0.074; p = 0.41). At 8 weeks, 52 patients (42%) had healed with
      complete symptoms resolution. No statistically significant differences were
      observed when clinical features and manometric and endosonographic findings were
      compared between healing and no-healing fissures. CONCLUSION: The majority of
      patients with chronic anal fissure present an abnormally thick IAS. Clinical,
      manometric and endosonographic features had no association with outcome after GTN
      treatment.

PMID- 17216218
TI  - Ultrasonographic patterns in patients with obstructed defaecation.
AB  - BACKGROUND: Anal ultrasound is helpful in assessing organic anorectal lesions,
      but its role in functional disease is still questionable. The purpose of the
      present study is to assess anal-vaginal-dynamic perineal ultrasonographic
      findings in patients with obstructed defecation (OD) and healthy controls.
      MATERIALS AND METHODS: Ninety-two consecutive patients (77 women; mean age 51
      years; range 21-71) with symptoms of OD were retrospectively evaluated. All
      patients underwent digital exploration, endoanal and endovaginal ultrasound (US)
      with rotating probe. Forty-one patients underwent dynamic perineal US with linear
      probe. Anal manometry and defaecography were performed in 73 and 43 patients,
      respectively. Ultrasonographic findings of 92 patients with symptoms of OD were
      compared to 22 healthy controls. Anismus was defined on US when the difference in
      millimetres between the distance of the inner edge of the puborectalis muscle
      posteriorly and the probe at rest and on straining was less then 5 mm.
      Sensitivity and specificity were calculated by assuming defaecography as the gold
      standard for intussusception and rectocele and proctoscopy for rectal internal
      mucosal prolapse. Since no gold standard for the diagnosis of anismus was
      available in the literature, the agreement between anal US and all other
      diagnostic procedures was evaluated. RESULTS: The incidence of anismus resulted
      significantly higher (P < 0.05) in OD patients than healthy controls on anal (48
      vs 22%), vaginal (44 vs 21%), and dynamic perineal US (53 vs 22%). A
      significantly higher incidence of rectal internal mucosal prolapse was observed
      in OD patients when compared to healthy controls on both anal (61.9 vs 13.6%, P <
      0.0001) and dynamic perineal US (51.2 vs.9% P = 0.001). For the diagnosis of
      rectal internal mucosal prolapse, anal US had a 100% sensitivity and specificity.
      For diagnosis of rectal intussusception, anal US had an 83.3% sensitivity and
      100% specificity and perineal US had a 66.6% sensitivity and 100% specificity. In
      the diagnosis of anismus, anal ultrasonography resulted in agreement with
      perineal and vaginal US, manometry, defaecography, and digital exam (P < 0.05).
      Other lesions detected by US in patients with OD include solitary rectal ulcer,
      rectocele and enterocele. Damage of internal and/or external sphincter was
      diagnosed at anal US in 19/92 (20%) patients, all continent and with normal
      manometric values. CONCLUSION: Anal, vaginal and dynamic perineal ultrasonography
      can diagnose or confirm many of the abnormalities seen in patients with OD. The
      value of the information obtained by this non-invasive test and its role in the
      diagnostic algorithm of OD is yet to be defined.

PMID- 17216219
TI  - Tumor budding as a prognostic marker in stage-III rectal carcinoma.
AB  - BACKGROUND AND AIM: Tumor budding along the invasive margin is known to be
      associated with biological behavior in colorectal carcinoma. The aims of this
      study were to explore if the semiquantitative assessment of tumor budding in
      rectal cancers correlates with oncological behavior and to appraise if the tumor
      budding is valid as a pathological parameter in distinguishing tumors with higher
      malignancy potential from those with lower one for prognostic stratification.
      MATERIALS AND METHODS: Surgical specimens from 244 patients with well- or
      moderately differentiated rectal carcinoma were retrieved to assess the intensity
      of tumor budding at the invasive margin. Intensities were divided
      semiquantitatively into four groups based on quartiles, and the 5-year disease
      free survivals (DFS) were analyzed to search for a cutoff point of prognostic
      stratification. RESULTS: The cutoff of the intensity considered to be the best
      indicator for dividing patients into subgroups with different DFS was between
      quartiles 3 and 4, but this survival difference in subgroups in either side of
      the cutoff was significant only in stage-III disease [5-year DFS, 62.1 vs 35.1%;
      p = 0.0023; 95% confidence interval (CI), 0.1824-0.6919]. Based on multivariate
      analysis, the intensity of budding proved to be an independent variable
      associated with DFS (hazard ratio, 2.005; p = 0.0086; 95% CI, 1.021-3.934). When
      scores were given to grade of budding (lower, 0; higher, 1) and N stage (N1, 0;
      N2, 1) in stage III, a better prognostic stratification in terms of the 5-year
      DFS was obtained than the American Joint Committee on Cancer nodal staging only
      (0 vs 1 vs 2, 66.5 vs 42.6 vs 29.2%; p = 0.0101). CONCLUSIONS: Quantitative
      assessment of tumor budding is a reliable biological prognostic variable to
      identify higher malignancy potential. Scoring system using tumor budding and N
      stage showed better prognostic stratification in stage-III rectal carcinoma. A
      prospective evaluation would confirm the clinical significance of tumor budding
      for prognostic stratification.

PMID- 17216220
TI  - Ten years experience of one-stage restorative proctocolectomy for ulcerative
      colitis.
AB  - BACKGROUND: Ileal-pouch anal anastomosis has an established role in the treatment
      of ulcerative colitis. Controversy exists regarding the routine use of a
      diverting ileostomy. The aim of this study was to review the clinical and
      functional outcome of patients undergoing restorative proctocolectomy in the
      absence of a diverting ileostomy (one-stage). MATERIALS AND METHODS: Between 1990
      and 1999, 87 patients with ulcerative colitis underwent a one-stage restorative
      proctocolectomy. The median age at the time of operation was 34 years (range 12
      64 years) and median follow-up was 36 months (range 24-144 months). The clinical
      notes were reviewed retrospectively. RESULTS: The median in-patient stay was 15
      days (range 9-36). There were no post-operative deaths. The complication rate
      within 30 days of surgery approximated to 40%. The median daytime pouch
      evacuation rate was 5. Only 13% of patients had to empty their pouch at night on
      a regular basis. Pelvic sepsis secondary to anastomotic leakage was the most
      commonly encountered problem, occurring in 15 patients. Small bowel obstruction
      was encountered in ten patients. One pouch required excision for a recurrent
      pouch-vaginal fistula. CONCLUSION: Despite refinements in the surgical technique,
      restorative proctocolectomy is associated with significant morbidity. For a
      selected group of patients undergoing an ileo-anal anastomosis, a defunctioning
      ileostomy may be avoided.

PMID- 17216222
TI  - Letter to the editor: "Colorectal leukemia masquerading as acute Crohn's
      colitis".

PMID- 17216221
TI  - Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases
      apoptosis in normal colonic mucosa in subjects with a history of colorectal
      adenomas.
AB  - BACKGROUND AND AIMS: Omega-3 fatty acids in fish oil exert a protective effect on
      the development of colorectal cancer in animal models. Patients with colorectal
      adenomas have been shown to have increased crypt cell proliferation and decreased
      apoptosis in macroscopically normal appearing colonic mucosa. We investigated
      whether dietary supplementation with eicosapentaenoic acid (EPA) could alter
      crypt cell proliferation and apoptosis in such patients. PATIENTS/METHODS: Thirty
      subjects were randomised to either 3 months of highly purified EPA in free fatty
      acid form (2 g/day) or to no treatment. Colonic biopsies were taken at the
      initial colonoscopy and repeated 3 months later, and analysed for cell
      proliferation and apoptosis (immunohistochemistry) and mucosal fatty acid
      content. RESULTS/FINDINGS: Crypt cell proliferation was significantly reduced
      whilst apoptosis was significantly increased after EPA supplementation. Neither
      crypt cell proliferation nor apoptosis were altered in the control group. EPA in
      the mucosa increased significantly after EPA supplementation, whereas there was
      no significant change in controls. CONCLUSIONS: Dietary supplementation with EPA
      significantly increases levels of this fatty acid in colonic mucosa, associated
      with significantly reduced proliferation and increased mucosal apoptosis. Further
      studies are needed to assess the potential efficacy of EPA supplementation in
      preventing polyps in the chemoprevention of colorectal cancer.

PMID- 17216223
TI  - Polymorphic lymphoid proliferation presenting as ileocecal intussusception.

PMID- 17216224
TI  - CIRE1, a novel transcriptionally active Ty1-copia retrotransposon from Citrus
      sinensis.
AB  - LTR retrotransposons (LTR-RTNs) are widespread constituents of eukaryote genomes,
      particularly plant genomes. Although LTR-RTNs from plants were thought to be
      transcriptionally silent in somatic tissues, evidences of activity under certain
      conditions are available for some of them. In order to investigate LTR-RTNs in
      the Citrus sinensis genome, we analysed them by PCR using degenerate primers
      corresponding to highly conserved domains. All elements of the two types of LTR
      RTN comprise about 23% of the genome, the copia group contribution being higher
      (13%) than the gypsy one (10%). From dendogram analysis, we report seven new
      copia RTN families, named CIRE1 to CIRE7. Here, we report on the first complete
      retrotransposon identified in Citrus (named CIRE1), which has all the features of
      a typical copia RTN. CIRE1 retrotransposon has around 2,200 full-length copies,
      contributing to 2.9% of the C. sinensis genome. CIRE1 has a root-specific
      expression in sweet orange plants. We have also determined that wounding and
      exogenous application of plant hormones, as methyl jasmonate and auxin, increase
      the transcription level of CIRE1 in leaf tissues. In addition, we show that CIRE1
      5'LTR promoter can drive transient expression of the gus reporter gene in
      heterologous plant systems. These findings confirm CIRE1 as one of the few
      transcriptionally active RTNs described in plants and to our knowledge the first
      one to be reported in Citrus species.

PMID- 17216226
TI  - Multiple schwannomas: report of two cases.
AB  - In this paper authors present two cases of multiple schwannomas without the
      features of neurofibromatosis (NF). The authors retrospectively reviewed the
      hospital charts, radiology films, operative notes and pathology slides of these
      two patients. There was no family history of neurofibromatosis. The two patients
      had contrast enhanced MRI, which was negative for vestibular schwannomas. Both
      underwent surgical excision of symptomatic lesions. Histopathology confirmed
      these lesions as schwannomas. Molecular genetic analysis in case 1 demonstrated
      two distinct mutations of the NF2 gene in two different schwannomas, with
      concomitant loss of heterozygosity in both tumours. In contrast peripheral blood
      lymphocytes did not reveal mutations of NF2. The authors recommend surgery for
      symptomatic lesions. Asymptomatic tumours can be monitored. Regular follow up is
      essential as they may develop fresh lesions at any time. The relevant literature
      is discussed.

PMID- 17216225
TI  - Germ line transformation of the silkworm, Bombyx mori, using the transposable
      element Minos.
AB  - We investigated the use of Minos as a vector for transgenesis in the silkworm,
      Bombyx mori. We first constructed a vector plasmid with the green fluorescent
      protein (GFP) gene fused with the silkworm cytoplasmic actin gene (A3) promoter,
      and a helper plasmid with the Minos transposase gene controlled by the same A3
      promoter. Injection of the vector and helper plasmid DNA into silkworm eggs
      produced transgenic animals in the following generation. The efficiency of
      transgenic silkworm production using this method was much lower than that
      obtained using piggyBac-mediated germ line transformation. However, >40-fold
      increase in the efficiency of producing transgenic silkworms was obtained using
      an in vitro synthesized source of Minos transposase mRNA. We conclude that the
      Minos transposon is a useful vector for construction of transgenic silkworms,
      particularly when in vitro synthesized mRNA is used. This is the first report
      showing that Minos can be used as a vector for germ-line transformation in
      lepidopteran insects.

PMID- 17216228
TI  - Relation of inflammatory modic changes to intradiscal steroid injection outcome
      in chronic low back pain.
AB  - The purpose of this study was to analyze the association between the severity of
      inflammatory endplate changes (Modic) on MRI and the clinical response to
      intradiscal injection of corticosteroids (IDIC) in chronic low back pain (LBP). A
      total of 74 patients with LBP and inflammatory Modic changes who showed no
      response to 3-month conservative treatment received lumbar IDIC. Two spine
      specialists and a radiologist assessed independently the endplate marrow changes
      of the injected discs. We classified patients with a pure edema endplate changes
      on MRI as Modic type I (n = 37); those with a mixture of Modic type I and type II
      changes but predominantly edema changes as Modic I-2 (n = 25) and those with
      predominantly fatty changes as Modic II-1 (n = 12). The primary outcome was the
      change in LBP intensity between baseline and 1 month after IDIC, as measured on a
      visual analog scale (range 0-100 mm). At 1 month, reduction in pain score was
      significantly higher in the Modic I and Modic I-2 groups than in the Modic II-1
      group (30.2 +/- 26.6 and 29.4 +/- 21.5 vs 5.3 +/- 25.5; P = 0.009 and P = 0.017,
      respectively). At 3 and 6 months, IDIC tended to be more effective in the Modic I
      and Modic I-2 groups but not significantly. No complications such as infection or
      hematoma were reported. IDIC could be a short-term efficient treatment for
      patients with chronic LBP and predominantly inflammatory endplate changes when
      conservative treatments have failed.

PMID- 17216227
TI  - Quantitative analysis in outcome assessment of instrumented lumbosacral
      arthrodesis.
AB  - The outcome assessment in instrumented lumbosacral fusion mostly focuses on
      clinical criteria, complications and scores, with a high variability of imaging
      means, methods of fusion grading and parameters describing degenerative changes,
      making comparisons between studies difficult. The aim of this retrospective
      evaluation was to evaluate the interest of quantified radiographic analysis of
      lumbar spine in global outcome assessment and to highlight the key biomechanical
      factors involved. Clinical data and Beaujon-Lassale scores were collected for 49
      patients who underwent lumbosacral arthrodesis after prior lumbar discectomy
      (mean follow-up: 5 years). Sagittal standing and lumbar flexion-extension X-ray
      films allowed quantifying vertebral, lumbar, pelvic and kinematic parameters of
      the lumbar spine, which were compared to reference values. Statistics were
      performed to assess evolution for all variables. At long-term follow-up, 90% of
      patients presented satisfactory clinical outcomes, associated to normal sagittal
      alignment; vertebral parameters objectified adjacent level degeneration in four
      cases (8%). Clinical outcome was correlated (r = 0.8) with fusion that was
      confirmed in 80% of cases, doubtful in 16% and pseudarthrosis seemed to occur in
      4% (2) of cases. In addition to clinical data (outcomes comparable to the
      literature), quantitative analysis accurately described lumbar spine geometry and
      kinematics, highlighting parameters related to adjacent level's degeneration and
      a significant correlation between clinical outcome and fusion. Furthermore,
      criteria proposed to quantitatively evaluate fusion from lumbar dynamic
      radiographs seem to be appropriate and in agreement with surgeon's qualitative
      grading in 87% of cases.

PMID- 17216230
TI  - Origin of seed shattering in rice (Oryza sativa L.).
AB  - A critical evolutionary step during rice domestication was the elimination of
      seed shattering. Wild rice disperses seeds freely at maturity to guarantee the
      propagation, while cultivated rice retains seeds on the straws to make easy
      harvest and decrease the loss of production. The molecular basis for this key
      event during rice domestication remains to be elucidated. Here we show that the
      seed shattering is controlled by a single dominant gene, Shattering1 (SHA1),
      encoding a member of the trihelix family of plant-specific transcription factors.
      SHA1 was mapped to a 5.5 kb genomic fragment, which contains a single open
      reading frame, using a backcrossed population between cultivated rice Teqing and
      an introgression line IL105 with the seed shattering habit derived from perennial
      common wild rice, YJCWR. The predicted amino acid sequence of SHA1 in YJCWR and
      IL105 is distinguished from that in eight domesticated rice cultivars, including
      Teqing, by only a single amino acid substitution (K79N) caused by a single
      nucleotide change (g237t). Further sequence verification on the g237t mutation
      site revealed that the g237t mutation is present in all the domesticated rice
      cultivars, including 92 indica and 108 japonica cultivars, but not in any of the
      24 wild rice accessions examined. Our results demonstrate that the g237t mutation
      in SHA1 accounts for the elimination of seed shattering, and that all the
      domesticated rice cultivars harbor the mutant sha1 gene and therefore have lost
      the ability to shed their seeds at maturity. In addition, our data support the
      theory that the non-shattering trait selection during rice domestication occurred
      prior to the indica-japonica differentiation in rice evolutionary history.

PMID- 17216229
TI  - Physicochemical and MRI characterization of Gd3+-loaded polyamidoamine and
      hyperbranched dendrimers.
AB  - Generation 4 polyamidoamine (PAMAM) and, for the first time, hyperbranched
      poly(ethylene imine) or polyglycerol dendrimers have been loaded with Gd3+
      chelates, and the macromolecular adducts have been studied in vitro and in vivo
      with regard to MRI contrast agent applications. The Gd3+ chelator was either a
      tetraazatetracarboxylate DOTA-pBn4- or a tetraazatricarboxylate monoamide DO3A
      MA3- unit. The water exchange rate was determined from a 17O NMR and 1H Nuclear
      Magnetic Relaxation Dispersion study for the corresponding monomer analogues
      [Gd(DO3A-AEM)(H2O)] and [Gd(DOTA-pBn-NH2)(H2O)]- (kex298=3.4 and 6.6x10(6) s-1,
      respectively), where H3DO3A-AEM is {4-[(2-acetylaminoethylcarbamoyl)methyl]-7,10
      bis(carboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)}-acetic acid and H4DOTA-pBn
      NH2 is 2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
      acid. For the macromolecular complexes, variable-field proton relaxivities have
      been measured and analyzed in terms of local and global motional dynamics by
      using the Lipari-Szabo approach. At frequencies below 100 MHz, the proton
      relaxivities are twice as high for the dendrimers loaded with the negatively
      charged Gd(DOTA-pBn)- in comparison with the analogous molecule bearing the
      neutral Gd(DO3A-MA). We explained this difference by the different rotational
      dynamics: the much slower motion of Gd(DOTA-pBn)--loaded dendrimers is likely
      related to the negative charge of the chelate which creates more rigidity and
      increases the overall size of the macromolecule compared with dendrimers loaded
      with the neutral Gd(DO3A-MA). Attachment of poly(ethylene glycol) chains to the
      dendrimers does not influence relaxivity. Both hyperbranched structures were
      found to be as good scaffolds as regular PAMAM dendrimers in terms of the proton
      relaxivity of the Gd3+ complexes. The in vivo MRI studies on tumor-bearing mice
      at 4.7 T proved that all dendrimeric complexes are suitable for angiography and
      for the study of vasculature parameters like blood volume and permeability of
      tumor vessels.

PMID- 17216231
TI  - Larval feeding induced defensive responses in tobacco: comparison of two sibling
      species of Helicoverpa with different diet breadths.
AB  - Plants respond differently to damage by different herbivorous insects. We
      speculated that sibling herbivorous species with different host ranges might also
      influence plant responses differently. Such differences may be associated with
      the diet breadth (specialization) of herbivores within a feeding guild, and the
      specialist may cause less intensive plant responses than the generalist. The
      tobacco Nicotinana tabacum L. is the common host plant of a generalist
      Helicoverpa armigera (Hubner) and a specialist H. assulta Guenee (Lepidoptera,
      Noctuidae). The induced responses of tobacco to feeding of these two noctuid
      herbivores and mechanical wounding were compared. The results showed that the
      feeding of the specialist H. assulta and the generalist H. armigera resulted in
      the same inducible defensive system, but response intensity of plants was
      different to these two species. Inductions of jasmonic acid (JA), lipoxygenase
      (LOX), and proteinase inhibitors (PIs) were not significantly different
      concerning these two species, but H. assulta caused the less intensive foliar
      polyphenol oxidase (PPO) increase, more intensive nicotine and peroxidase (POD)
      increases in tobacco than H. armigera. The defensive response of plant to
      herbivores with different diet breadth seems to be more complicated than we
      expected, and the specialist does not necessarily cause less intensive plant
      responses than the generalist.

PMID- 17216232
TI  - Silencing of NbBTF3 results in developmental defects and disturbed gene
      expression in chloroplasts and mitochondria of higher plants.
AB  - BTF3 (betaNAC) was originally isolated as a general transcription factor required
      for RNA polymerase II-dependent transcription, and later found to be a beta
      subunit of nascent-polypeptide-associated complex that has been implicated in
      regulating protein localization during translation. In this study, virus-induced
      gene silencing of NbBTF3 encoding a Nicotiana benthamiana homolog of human BTF3
      caused leaf yellowing and abnormal leaf morphology without altering the overall
      growth of the plant. The NbBTF3 gene is constitutively expressed and the NbBTF3
      GFP fusion protein is primarily targeted to the nucleus. At the cellular level,
      downregulation of NbBTF3 expression reduced the chloroplast sizes and chlorophyll
      contents. The affected cells produced excessive amounts of reactive oxygen
      species. Furthermore, the transcript level of various plastid- and mitochondria
      encoded genes was severely reduced in the NbBTF3-depleted leaf cells. These
      findings indicate that depletion of NbBTF3 activity preferentially affected
      development and/or physiology of chloroplasts and mitochondria in plants,
      possibly by hampering efficient translocation of the nascent organellar proteins
      into the organelles.

PMID- 17216233
TI  - Erdosteine treatment attenuates oxidative stress and fibrosis in experimental
      biliary obstruction.
AB  - Oxidative stress, in particular lipid peroxidation, induces collagen synthesis
      and causes fibrosis. The aim of this study was to assess the antioxidant and
      antifibrotic effects of erdosteine on liver fibrosis induced by biliary
      obstruction in rats. Liver fibrosis was induced in Wistar albino rats by bile
      duct ligation (BDL). Erdosteine (10 mg/kg, orally) or saline was administered for
      28 days. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT)
      and lactate dehydrogenase (LDH) levels were determined to assess liver functions
      and tissue damage, respectively. Pro-inflammatory cytokines, TNF-alpha, IL-1beta
      and IL-6 and antioxidant capacity (AOC) were assayed in plasma samples. Liver
      tissues were taken for determination of malondialdehyde (MDA) and glutathione
      (GSH) levels, myeloperoxidase (MPO) activity and collagen content. Production of
      reactive oxidants was monitored by chemiluminescence assay. Serum AST, ALT, LDH,
      and plasma cytokines were elevated in the BDL group as compared to controls and
      were significantly decreased by erdosteine treatment. Hepatic GSH level and
      plasma AOC, depressed by BDL, were elevated back to control level with erdosteine
      treatment. Furthermore, hepatic luminol and lucigenin chemiluminescence (CL), MDA
      level, MPO activity and collagen content in BDL group increased dramatically
      compared to control and reduced by erdosteine treatment. Since erdosteine
      administration alleviated the BDL-induced oxidative injury of the liver and
      improved the hepatic functions, it seems likely that erdosteine with its
      antioxidant and antifibrotic properties, may be of potential therapeutic value in
      protecting the liver fibrosis and oxidative injury due to biliary obstruction.

PMID- 17216234
TI  - Factors predicting failure of redo Nissen fundoplication in children.
AB  - Recurrence of gastro-oesophageal reflux (GOR) following redo Nissen
      fundoplication represents a significant clinical problem. The aim of this study
      was to identify factors predicting failure of redo Nissen fundoplication. The
      notes of children who underwent redo Nissen fundoplication for recurrent GOR in a
      single institution between June 1994 and May 2005 were reviewed. Data are
      reported as median (range), or as numbers of cases. Multiple logistic regression
      analysis, using type of first fundoplication, neurological status, presence of
      gastrostomy, age-weight, retching-gas bloat after first fundoplication,
      associated anomalies, oesophageal atresia and length of follow-up as factors, was
      used to generate a model to identify factors predicting recurrent vomiting
      (failure) after redo. Eighty-one children underwent redo Nissen fundoplication
      15.9 months (0.2-176) after the initial Nissen fundoplication. In 29, the first
      Nissen was laparoscopic. Age at redo Nissen fundoplication was 3.3 years (0.3
      15.9) and weight 12.8 kg (5-60). Thirty-four children (42%) presented with
      recurrent vomiting (failure). Overall, the model successfully predicted vomiting
      (failure) after redo fundoplication (P = 0.009). Open surgery at first
      fundoplication (P = 0.011) and neurological impairment (P = 0.046) were both
      significant predictors of redo failure in the model, whereas presence of
      gastrostomy (P = 0.035) and older-heavier age-weight (P = 0.028) were associated
      with significantly better results. Retching-gas bloat, associated anomalies and
      oesophageal atresia were not significant predictors of failure. Redo Nissen
      fundoplication has a high failure rate. Risk factors are open fundoplication at
      first operation and neurological impairment. Redo fundoplication after primary
      laparoscopic Nissen has a lower risk of failure.

PMID- 17216235
TI  - [The biology of visceral fat].
AB  - Visceral obesity is an independent risk factor for the development of
      cardiovascular diseases and type 2 diabetes. This is likely to be due to
      biological characteristics of visceral tissue, which are different from those of
      subcutaneous adipose tissue in terms of decreased insulin sensitivity and
      increased lipolytic activity. In addition, the anatomical site of visceral fat
      could be one potential reason for the increased cardio-metabolic risk associated
      with visceral obesity. Visceral adipose tissue drains into the portal vein and
      therefore the liver is exposed to the undiluted metabolites and adipokines
      released from visceral fat. There are profound differences between visceral and
      subcutaneous adipocytes in the metabolism, expression of specific receptors and
      secretion of a specific adipokine pattern, which could contribute to the adverse
      consequences of visceral obesity.

PMID- 17216236
TI  - [Female patients with arterial hypertension].
AB  - In Germany, more women than men die from cardiovascular causes. Women account for
      more than two thirds of the patients who die as a direct consequence of high
      blood pressure. Although arterial hypertension is a major risk factor for
      cardiovascular disease, and many drugs are available for hypertension treatment,
      less than 30% of hypertensive patients in Germany are controlled. There is a
      striking age-dependent development of blood pressure values in women compared to
      men. Blood pressure is lower in younger women than in men, a fact that likely
      contributes to the reduced cardiovascular risk in younger women. Hormonal changes
      that occur with menopause are thought to lead to an increase in cardiovascular
      risk in postmenopausal women to match that of men in the same age-group. To date,
      women and men are treated according to the same guidelines, since large studies
      have established a reduction in cardiovascular endpoints as a result of
      hypertension treatment. The database on putative differences in the effects and
      side-effects, as well as the effectiveness of the various classes of
      antihypertensive drugs dependent on gender is limited but growing.

PMID- 17216237
TI  - Development and validation of a cell culture based assay for in vitro assessment
      of anticryptosporidial compounds.
AB  - In vitro culture of Cryptosporidium parvum oocysts in HCT-8 cells was combined
      with immunofluorescent labelling and digital image analysis to quantify the
      development of the parasite by detecting and measuring the labelled area in the
      respective cell cultures. The number of inoculated oocysts and the labelled area
      correlated reliably and significantly (R (2), 0.98-0.99). The effects of various
      concentrations of halofuginone bromide (0.00039 to 50 microM) and monensin
      (0.00225 to 0.144 microM) on in vitro parasite development were determined in
      further trials in cultures inoculated each with 10(5) oocysts. Monensin reduced
      the detected area in a dose-dependant manner. In comparison to the untreated
      controls, the area positive for C. parvum in the cultures treated with 0.144 to
      0.009 microM monensin reached a maximum of 17%, and inhibition of 40% was
      observed at 0.0045 microM. Halofuginone bromide also efficiently inhibited
      parasite in vitro reproduction, albeit at higher concentrations. At 12.5 microM
      or more, inhibition was at least 90%; 0.05 microM still yielded 80% inhibition,
      whereas at concentrations below 0.00625 microM, labelled areas abruptly
      increased. Both drugs appeared efficient under in vitro conditions; the applied
      system is suited to screen drugs for their anti-cryptosporidial capacity.

PMID- 17216238
TI  - Evaluation of a serological method for the detection of Taenia saginata
      cysticercosis using serum and meat juice samples.
AB  - Two peptides, HP6-2 and Ts45S-10, were used as antigens for the detection of
      antibodies against Taenia saginata cysticercosis in serum and meat juice samples
      using enzyme-linked immunosorbent assay (ELISA). Positive control samples were
      obtained from animals experimentally infected (serum) and from animals naturally
      infected (meat juice). The two peptides and a pooled preparation of both peptides
      were evaluated, and their cut-off points with both sample categories were
      calculated. ELISA results from these different peptides were compared.
      Sensitivity and specificity of HP6-2 using serum were calculated as being 100 and
      98%, respectively, showing to be higher than the values for the other antigens
      used. The average optical density (OD) value for negative samples was 0.646,
      whereas it was 1.702 for the positive control samples. This peptide was used to
      examine serum samples from animals with cysts and random field serum samples. For
      meat juice samples the pooled peptides showed the highest sensitivity and
      specificity, as they were 100 and 95%, respectively. The average OD values for
      the negative and the positive reference meat juice samples were 0.379 and 1.291,
      respectively. The optimal dilution of the meat juice samples for the ELISA was
      very low, as it was 1:20 using the pooled peptides, compared with 1:800 serum
      dilution using HP6-2. To the authors' knowledge, this is the first report of a
      successful testing for T. saginata cysticercosis using meat juice.

PMID- 17216239
TI  - Fine structure of Chrysomya nigripes (Diptera: Calliphoridae), a fly species of
      medical importance.
AB  - The fine structure of Chrysomya nigripes Aubertin, a blow fly species of medical
      importance, is presented using scanning electron microscopy (SEM) to contribute
      information on the morphology of the adult of this fly species. The surface of
      the dome-shaped ommatidia exhibits a microscopic granulose appearance. The palpus
      is equipped with small sensilla basiconica and sensilla chaetica, which provide
      sensory reception for detecting environmental information. At the apex of the
      mouthparts, the labellum is endowed with large numbers of sensilla trichodea and
      basiconic-like sensilla of variable length. The anterior (mesothoracic) spiracle
      is elliptical in shape and covered with extensively ramified setae except for a
      small dorsal aperture. The posterior (metathoracic) spiracle is shaped like a
      rounded isosceles triangle and covered by two valves of unequal size. The larger
      valve covers the upper approximately 2/3 of the spiracular opening, whereas the
      smaller valve covers the lower approximately 1/3 of the opening. Extensively
      ramified setae line and cover the valves over the entire spiracle. SEM analyses
      of the haltere knob and the prosternal organs, located adjacent to the cervical
      sclerites, revealed a striking resemblance of the morphological features of their
      sensilla. Each sensillum emanates from a cuticular ring, is approximately 12-15
      mum in length, has a smooth surface, and terminates in a sharp tip. Various types
      of sensilla were associated with the ovipositor including sensilla trichodea,
      sensilla basiconica, sensilla placodea and probably sensilla styloconica. The
      possible function of sensilla distributed in particular regions of the fly
      integument is discussed.

PMID- 17216241
TI  - Infection pattern of two sympatric acanthocephalan species in the amphipod
      Hyalella patagonica (Amphipoda: Hyalellidae) from Lake Mascardi (Patagonia,
      Argentina).
AB  - The aim of the present study was to describe the infection pattern of the
      acanthocephalans Acanthocephalus tumescens and Corynosoma sp. co-occurring in the
      intermediate host the amphipod Hyalella patagonica. Samples were collected
      monthly from June 2002 to May 2004 from Lake Mascardi. Amphipods were measured
      and classified by developmental stages. Single and double infections of larval
      acanthocephalans were recorded and prevalence and mean intensity were calculated.
      An annual life cycle of H. patagonica could be inferred with recruitment of
      juveniles from spring to autumn. Males and females were found all year round but
      females were significantly more abundant. Single infections were mainly found in
      smaller juvenile amphipods during winter for A. tumescens and in intermediate and
      large male amphipods during spring and summer for Corynosoma sp. Double
      infections showed low values and were mainly found in intermediate sized
      amphipods during spring. A segregation of the infection by season, size and
      developmental stages of the host was recorded and would tend to avoid competition
      considering these two acanthocephalan species have different definitive hosts:
      fishes for A. tumescens and aquatic birds for Corynosoma sp.

PMID- 17216240
TI  - Mitochondrial haplotype diversity of Gyrodactylus thymalli (Platyhelminthes;
      Monogenea): extended geographic sampling in United Kingdom, Poland, and Norway
      reveals further lineages.
AB  - In recent years, the mitochondrial haplotype diversity of the monogenean
      ectoparasites Gyrodactylus salaris Malmberg, 1957 on Atlantic salmon and G.
      thymalli Zitnan, 1960 on grayling has been studied intensively to understand the
      taxonomy and phylogeography of the two species. According to these studies,
      neither species can be considered monophyletic, but unfortunately, the geographic
      sampling has mostly been restricted to Fennoscandia. Only few samples from
      continental Europe have been analysed, and samples from the United Kingdom have
      not been included at all. Gyrodactylosis is a notifiable disease in Europe and is
      in the UK considered the most important exotic disease threat to wild Atlantic
      salmon populations. In this study, we report six new mitochondrial haplotypes of
      G. thymalli from England, Poland, and Norway detected by sequencing 745 bp of the
      cytochrome oxidase I gene. The six new haplotypes add five new clades to a
      neighbor-joining dendrogram deduced on the basis of the currently known 44
      mitochondrial haplotypes for G. thymalli and G. salaris. We conclude that G.
      thymalli established in the UK along with the immigration of grayling. There is
      currently no reason to suspect that this parasite is a threat to Atlantic salmon
      in the UK, although its infectivity to salmon stocks in the UK has not been
      tested.

PMID- 17216242
TI  - Seasonal dynamics in the numbers of parasitic bugs (Heteroptera, Cimicidae): a
      possible cause of roost switching in bats (Chiroptera, Vespertilionidae).
AB  - The objective of the present paper is to extend the knowledge of roosting
      strategies of bats and the interaction of bats with their roost ectoparasites,
      the bat bugs Cimex pipistrelli. The project was focussed on the potential
      causality of bat movements and the variation in bug numbers. For 2 years, three
      model bat boxes with breeding female Pipistrellus pygmaeus were monitored inside
      floodplain forest. After the arrival of bats in May, adults and first instars of
      bugs were observed in the boxes. During the lactation period in June, when the
      bats did not occupy the roosts, the first instar bugs died out followed by the
      adults. The decrease in bug numbers began only several days after the bats had
      left the boxes. After a month of the bats' absence, the abundance of adult bugs
      decreased by half of their number. Only the eggs survived the period when the
      roosts were unoccupied in summer. In mid-July, after the arrival of lactating
      females, an increase in the number of bugs was observed. At the beginning of
      August, however, no new eggs were found. Although adult C. pipistrelli are able
      to survive the winter period in the boxes, the bats, by shifting the roosts
      within the vegetation season, prevent the massive reproduction of these
      parasites.

PMID- 17216243
TI  - Effects of freezing on the biomechanical and structural properties of human
      posterior tibial tendons.
AB  - This work analyzes the effects of storage by fresh-freezing at -80 degrees C on
      the histological, structural and biomechanical properties of the human posterior
      tibial tendon (PTT), used for ACL reconstruction. Twenty-two PTTs were harvested
      from eleven donors. For each donor one tendon was frozen at -80 degrees C and
      thawed in physiological solution at 37 degrees C, and the other was tested
      without freezing (control). Transmission electron microscopy (TEM), differential
      scanning calorimetry (DSC) and biomechanical analysis were performed. We found
      the following mean changes in frozen-thawed tendons compared to controls: TEM
      showed an increase in the mean diameter of collagen fibrils and in fibril non
      occupation mean ratio, while the mean number of fibrils decreased; DSC showed a
      decrease in mean denaturation temperature and denaturation enthalpy.
      Biomechanical analysis showed a decrease in ultimate load and ultimate stress, an
      increase in stiffness and a decrease in ultimate strain of tendons. In conclusion
      fresh-freezing brings about significant changes in the biomechanical and
      structural properties of the human PTT. A high variability exists in the
      biophysical properties of tendons among individuals and in the effects of storage
      on tendons. Therefore, when choosing an allograft tendon, particular care is
      needed to choose a biomechanically suitable graft.

PMID- 17216244
TI  - Long-term results after a triple arthrodesis of the hindfoot: function and
      satisfaction in 36 patients.
AB  - The long-term functional results of a triple arthrodesis of the hindfoot are not
      well known. In this retrospective cohort study we therefore investigated pain,
      function and alignment of the tibiotalar joint, patient satisfaction with the
      procedure and the prevalence of osteoarthritis (OA) of the tibiotalar joint after
      a median follow-up of six years. We also aimed to investigate whether there are
      patient and surgical characteristics associated with the outcome. Patients who
      underwent a triple arthrodesis for OA between January 1992 and July 2002 were
      invited to participate. A clinical examination was performed, the Ankle-Hindfoot
      Scale was completed, and radiographs were taken. Patient characteristics (e.g.,
      age, gender and the indication for operation) and surgical characteristics (e.g.,
      fixation material and use of bone graft) were collected. Sixty-one percent (22
      patients) of the patients had a good total score on the Ankle-Hindfoot Scale.
      Nineteen patients (53%) were satisfied with the result of the operation and 47%
      of the patients had radiographic OA of the tibiotalar joint. In a univariate
      regression analysis, male gender and the score on the Ankle-Hindfoot Scale were
      significantly associated with radiographic OA. Patient satisfaction was
      significantly associated with a higher score on the Ankle-Hindfoot Scale and
      better dorsi-flexion of the ankle. Our study shows that 61% of the procedures in
      36 patients with a triple arthrodesis for OA had a good score on the Ankle
      Hindfoot Scale. Radiographic OA of the ankle was present in 47% of the cases and
      was not related to patient satisfaction. No patient characteristics or surgical
      characteristics were associated with the score on the Ankle-Hindfoot Scale.

PMID- 17216245
TI  - Lack of NPHP2 mutations in a newborn infant with Joubert syndrome-related
      disorder presenting as end-stage renal disease.
AB  - A newborn infant with end-stage renal disease (ESRD) due to nephronophthisis
      (NPHP) developed episodes of tachypnea, alternating with apnea, and abnormal eye
      movements. Contrast-enhanced magnetic resonance imaging (MRI) of the midbrain
      demonstrated the characteristic appearance of molar tooth sign on axial images,
      consistent with the diagnosis of Joubert syndrome (JBTS). The DNA sequence
      analysis of the polymerase chain reaction (PCR) detected no mutations in the
      NPHP2 (INVS) gene in this child, suggesting that new mutant genes might be
      responsible for the early onset of ESRD in infantile NPHP with features of JBTS.

PMID- 17216246
TI  - Severe anemia caused by the angiotensin receptor blocker irbesartan after renal
      transplantation.

PMID- 17216247
TI  - A multicenter study of the pharmacokinetics of lisinopril in pediatric patients
      with hypertension.
AB  - The pharmacokinetic (PK) parameters of lisinopril were obtained in 46 children
      aged 6 months to 15 years. A lisinopril suspension (0.15 mg/kg per day) was
      administered to patients <6 years of age; the remaining children received
      lisinopril tablets, the daily dose being adjusted according to body weight, i.e.,
      2.5 mg if <25 kg, 5 mg if 25-45 kg, and 10 mg if >45 kg. Blood was drawn predose
      and on eight occasions postdose in children aged 4-15 years, and on five
      occasions in those aged <4 years. PK data are reported for the 46 children in
      terms of age groups: Group I (n=9), aged 6-23 months; Group II (n=8), aged 2-5
      years; Group III (n=12), aged 6-11 years; Group IV (n=17), aged 12-15 years. The
      dose of lisinopril ranged from 3.07 mg/m(2) per day in Group I to 4.78 mg/m(2)
      per day in Group IV. C(max) of lisinopril, which occurred 5-6 h postdose, varied
      from 22 ng/ml in Groups I and II to 44 ng/ml in Groups III and IV; AUC(0-24 h)
      ranged from 301-311 ng.h/ml in Groups I and II to 550-570 ng.h/ml in Groups III
      and IV. No serious adverse events related to lisinopril were reported.

PMID- 17216248
TI  - How to define anemia in children with chronic kidney disease?
AB  - In a cross-sectional study, we compared the prevalence of anemia based on age-
      and gender-specific reference intervals for hemoglobin (Hgb) and hematocrit (Hct)
      with the Kidney Disease Outcomes Quality Initiative (KDOQI) anemia definition
      (Hgb < 110 g/L) in 351 children with chronic kidney disease (CKD) stages I-V.
      Cystatin C-based GFRs were 122 +/- 36 mL/min/1.73 m(2) in patients with stage I
      CKD (n=196), 76 +/- 8 mL/min/1.73 m(2) for stage II (n=104), 45 +/- 9 mL/min/1.73
      m(2) for stage III (n=36), and 22 +/- 5 mL/min/1.73 m(2) in patients with stage
      IV+V CKD (n=15). Fifty-nine patients received iron therapy and 32 patients were
      treated with Darbepoetin. For Hgb, a total of 90 patients fit the age and gender
      derived criteria, compared to only 54 patients identified by the KDOQI guidelines
      (p=0.0010). Similarly, for Hct, a total of 78 patients fit the age and gender
      derived criteria, which was a significantly higher proportion than the 56
      identified by the KDOQI guidelines (r=0.22, p=0.0435). There was a significant
      correlation between the GFR and both the Hgb Z-score (p=0.0068) and the Hct Z
      score (p=0.0128). There was poor agreement between conventional and KDOQI
      definitions of anemia in children with CKD.

PMID- 17216249
TI  - Imaging strategies for vesicoureteral reflux diagnosis.
AB  - The prevalence of vesicoureteral reflux (VUR), although reported to be low in the
      general population, is high in children with urinary tract infection (UTI), first
      degree relatives of patients with known VUR and children with antenatal
      hydronephrosis. In addition, it has been shown that VUR and UTIs are associated
      with renal scarring, predisposing to serious long-term complications, i.e.,
      hypertension, chronic renal insufficiency and complications of pregnancy.
      Therefore, diagnostic imaging for the detection of VUR in the high-risk groups of
      children has been a standard practice. However, none of these associations has
      been validated with controlled studies, and recently the value of identifying VUR
      after a symptomatic UTI has been questioned. In addition, several studies have
      shown that renal damage may occur in the absence of VUR. On the other hand, some
      patients, mainly males, may have primary renal damage, associated with high-grade
      VUR, without UTI. Recently, increasing skepticism has been noted concerning how
      and for whom it is important to investigate for VUR. It has been suggested that
      the absence of renal lesions after the first UTI in children may rule out VUR of
      clinical significance and reinforces the redundancy of invasive diagnostic
      techniques. Therefore, the priority of imaging strategies should focus on early
      identification of renal lesions to prevent further deterioration.

PMID- 17216250
TI  - Association of isolated preauricular tags and nephrourological anomalies: case
      control study.
AB  - Isolated preauricular tags (IPT) are considered minor malformations whereas
      nephrourological anomalies (NUA) are considered major malformations. Their
      incidences fluctuate between 5 and 10 per 1,000 and 1-3 per 100 live births,
      respectively. There is contradictory evidence regarding the incidence of NUA in
      infants with IPT. The objective of this study is to determine if there is a
      clinical association between IPT and NUA. A case-control study was made in a
      Pediatric hospital in Santiago, Chile, with infants born between April 2000 and
      April 2005, considering as cases those with IPT, and controls those infants born
      following the cases, paired by sex and without IPT. All subjects had a complete
      physical examination and a renal ultrasound to assess for the presence of
      congenital anomalies and NUA, respectively. One hundred cases and an equal number
      of controls were included. There were 41 females in each group. In the case
      group, two infants presented renal anomalies in the RUS: one left hydronephrosis
      and one case of left kidney agenesis. In the control group, two infants with
      anomaly were found: one with a left ureterocele and one case of bilateral duplex
      kidney. The observed incidence of NUA was similar in both groups to that reported
      in the literature for the general population. No significant statistical
      difference was found in the incidence of these abnormalities between patients who
      presented with IPT and those who did not. From our study, we suggest that RUS is
      not necessary in the routine evaluation of infants with IPT.

PMID- 17216251
TI  - Nine novel COL4A3 and COL4A4 mutations and polymorphisms identified in inherited
      membrane diseases.
AB  - Both thin basement membrane nephropathy (TBMN) and autosomal recessive Alport
      syndrome result from mutations in the COL4A3 and COL4A4 genes, and this study
      documents further mutations and polymorphisms in these genes. Thirteen unrelated
      children with TBMN and five individuals with autosomal recessive Alport syndrome
      were examined for mutations in the 52 exons of COL4A3 and the 47 coding exons of
      COL4A4 using single-stranded conformation polymorphism (SSCP) analysis. Amplicons
      producing different electrophoretic patterns were sequenced, and mutations were
      defined as variants that changed an amino acid but were not present in 50 non
      hematuric normals. Three further novel mutations were identified. These were IVS
      22-5 T>A in the COL4A3 gene in a consanguineous family with autosomal recessive
      Alport syndrome, and R1677C and R1682Q in the COL4A4 gene. In addition, six novel
      polymorphisms (G455G, I462I, G736G and IVS 38-8 G>A in COL4A3, and L658L and
      A1577A in COL4A4) were demonstrated.Many different COL4A3 and COL4A4 mutations
      cause TBMN and autosomal recessive Alport syndrome. The identification of
      polymorphisms in these genes is particularly important to enable diagnostic
      laboratories to distinguish mutations from uncommon normal variants.

PMID- 17216252
TI  - Diagnosis of de novo localized thrombotic microangiopathy by surveillance biopsy.
AB  - Thrombotic microangiopathy has been reported in association with calcineurin
      inhibitors and less frequently with sirolimus in renal transplant patients. The
      diagnosis of thrombotic microangiopathy is typically made by diagnostic biopsy in
      the setting of allograft dysfunction. The finding of thrombotic microangiopathy
      on surveillance biopsy without a significant elevation of baseline serum
      creatinine is unusual. The optimal treatment of this disorder remains
      controversial. Treatment strategies have included dose adjustment, drug
      substitution, plasmapheresis, and intravenous immunoglobulin G. We report a case
      of de novo thrombotic microangiopathy diagnosed by surveillance biopsy in a
      patient without hematologic abnormalities or elevated serum creatinine. This
      patient had resolution of the renal lesion following conversion from tacrolimus
      to sirolimus-based immunosuppression.

PMID- 17216253
TI  - Do mutations in COL4A1 or COL4A2 cause thin basement membrane nephropathy (TBMN)?
AB  - Thin basement membrane nephropathy (TBMN) is the commonest cause of persistent
      glomerular haematuria and often presents in childhood. Only 40% of affected
      individuals have mutations identified in the COL4A3 and COL4A4 genes, but
      mutations in the genes for other COL4A isoforms also result in thinned membranes
      in humans (COL4A5) and mice (COL4A1). This study examined whether COL4A1/COL4A2
      represented a further genetic locus for TBMN. Nine families with TBMN in whom
      haematuria did not segregate with COL4A3/COL4A4, were examined for linkage to
      COL4A1/COL4A2 using five micro-satellite markers. In addition, index cases from
      these families plus a further 14 unrelated individuals with TBMN that was not due
      to COL4A3 or COL4A4 mutations (n=23) were screened for mutations in each of the
      52 exons of COL4A1 and the 47 exons of COL4A2 using single stranded
      conformational analysis (SSCA). DNA samples that demonstrated bandshifts were
      sequenced. Haplotype analysis demonstrated that haematuria segregated with the
      COL4A1/COL4A2 locus in only two small families (2/9, 22%). No definite COL4A1 or
      COL4A2 mutations were identified in the 23 unrelated individuals with TBMN
      although novel polymorphisms were demonstrated. This study indicates that
      COL4A1/COL4A2 does not represent a further major genetic locus for TBMN.

PMID- 17216254
TI  - Embryology and genetics of primary vesico-ureteric reflux and associated renal
      dysplasia.
AB  - Congenital anomalies of the kidney and urinary tract, as well as primary vesico
      ureteric reflux (VUR) and associated renal dysplasia, are the most relevant
      causes of end-stage renal failure in the pediatric population. In vivo and in
      vitro experimental studies have allowed the identification of several genes
      involved both in ureteric bud branching, ureteric elongation and insertion into
      the bladder, and in nephrogenesis. It has been proposed that both renal and
      ureteral abnormalities, as well as the associated renal hypo-dysplasia, may
      derive from a common mechanism as the result of a dysregulation of the normal
      developmental program. The large homologies between mice and the human genome
      suggest that the same genes could be involved both in rodent and human VUR.
      Furthermore, epidemiological observations suggest that not only syndromic but
      also isolated VUR is an inherited trait. Linkage analysis for homologous mouse
      genes in humans, genome-wide linkage studies in multigenerational families and
      association studies by polymorphisms support the hypothesis that VUR is
      genetically heterogeneous and is caused by a number of different genes acting
      with random environmental effects. The present teaching paper is an overview of
      the embryology and genetics of primary VUR and associated congenital reflux
      nephropathy.

PMID- 17216255
TI  - Ambulatory blood pressure monitoring and renal functions in children with a
      solitary kidney.
AB  - The aim of this study is to investigate the blood pressure (BP) profile,
      microalbuminuria, renal functions, and relations with remaining normal kidney
      size in children with unilateral functioning solitary kidney (UFSK). Sixty-six
      children with UFSK were equally divided into three groups: unilateral renal
      agenesis (URA), unilateral atrophic kidney (UAK), and unilateral nephrectomy
      (UNP). Twenty-two age-, weight-, and height-matched healthy children were
      considered as a control group. The serum creatinine level and first-morning urine
      microalbumin and creatinine concentrations were determined by the standard
      methods. Also, the BP profile was determined by ambulatory blood pressure
      monitoring (ABPM). We found that the serum creatinine level was higher and
      creatinine clearance was lower in each patient groups compared to those of the
      control group (p < 0.05). Compared with the controls, each group of patients had
      mean office, 24-h, daytime, and night-time systolic and diastolic BP values
      similar to those of the controls (p > 0.05). An inverse correlation was found
      between the renal size standard deviation scores (SDS) of normal kidneys and 24-h
      systolic and diastolic BP load SDS in all of the patients (p < 0.05; r = -0.372,
      r = -0.295, respectively). The observed relationship between renal size SDS and
      24-h mean arterial pressure (MAP), systolic and diastolic BP load SDS suggests
      that children with UFSK should be evaluated by using ABPM for the risk of
      hypertension.

PMID- 17216256
TI  - A case of nephrogenic diabetes insipidus with a novel missense mutation in the
      AVPR2 gene.
AB  - We describe a pediatric case of nephrogenic diabetes insipidus (NDI) with a novel
      missense mutation in the arginine vasopressin receptor 2 (AVPR2) gene. The
      patient, a 3-year-old boy, had polyuria (4357 ml/day, 7230 ml/m(2)/day) and
      polydipsia. Water deprivation testing demonstrated no decrease of urine volume,
      and urinary volume did not respond to subcutaneous injection of 0.1 U/kg
      pitressin. Molecular genetic analysis demonstrated that the patient had an AVPR2
      missense mutation involving substitution of phenylalanine for tyrosine at
      position 205 (Y205F). It was also found that the patient's mother was
      heterozygous for this Y205F mutation. Analysis of the intermolecular interaction
      of the Tyr-205 hydrogen group by molecular modeling showed that Tyr-205 was
      located in transmembrane domain (TM) 5, and that its hydroxy group formed a
      hydrogen bond with Leu-169 main-chain =O located in TM 4. The mutation of Tyr-205
      to phenylalanine would cause loss of this hydrogen bond and decrease or change
      the interaction between these TM coils, thus affecting the ability of AVP to bind
      to the receptor. According to this molecular model of AVPR2, the Y205F mutation
      would cause nephrogenic diabetes insipidus.

PMID- 17216257
TI  - Normative data on the Bonn Risk Index for calcium oxalate crystallization in
      healthy children.
AB  - Bonn Risk Index (BRI) is being used for the assessment of urinary calcium oxalate
      (CaOx) crystallization. There are no published data regarding BRI during growth.
      The objective of this study was to establish age- and sex-dependent BRI values in
      healthy children and adolescents. A total of 1,050 Caucasian subjects aged 3-18
      years (525 males, 525 females) without a history of kidney stone disease were
      enrolled in the cross-sectional study. The study group was divided into 15 ranges
      according to age, each comprising 70 subjects. Urinary ionized calcium [Ca2+] was
      measured using a selective electrode while the onset of spontaneous
      crystallization was determined using a photometer and titrating with 40 mmol/L
      ammonium oxalate (Ox(2-)). The calculation of BRI value was based on the ratio of
      [Ca2+] to the required amount of ammonium oxalate added to 200 ml of urine to
      induce crystallization. The median BRI was 0.26 1/L and the values of the 5th and
      95th percentiles were 0.06 1/L and 1.93 1/L, respectively. BRI correlated
      positively with body-area-related BRI (1/L x 1.73 m2) (R = 0.18; P < 0.05),
      whereas a negative correlation was found between BRI and body weight (1/L x kg)
      (R = -0.85; P < 0.05). Neither sex nor age differences were detected in BRI
      across studied children and adolescents. The values of Bonn Risk Index were
      constant during growth and there was a limited influence of age and sex on BRI in
      children over 3 years of age. The BRI may be valuable in the evaluation of
      pediatric patients at risk for kidney stones, particularly if the BRI from stone
      formers is demonstrated to be higher than in normal children.

PMID- 17216258
TI  - Effect of haemodialysis on markers of bone turnover in children.
AB  - 'Intact' parathyroid hormone (iPTH) assays are used to measure serum PTH levels
      in haemodialysis patients to diagnose and monitor secondary hyperparathyroidism
      and consequent renal osteodystrophy (ROD); these assays exhibit cross-reactivity
      with long carboxyl-terminal PTH fragments (C-PTH) that accumulate in end stage
      renal failure (ESRF) and antagonise the biological activity of the whole
      molecule, 1-84 PTH. The effects of haemodialysis on C-PTH are not known. We
      investigated how haemodialysis affects serum concentrations of calcium, iPTH, 1
      84 PTH, C-PTH, and other markers of bone turnover; bone-specific alkaline
      phosphatase (BALP) and type 1 collagen cross-linked telopeptide (CTx). Fifteen
      patients, mean (range) age 13.9 (4.3-17.6) years, haemodialysed for a median of
      16.3 (4-41) months, had pre- and post-dialysis serum samples collected for
      routine biochemistry, BALP, CTx, iPTH and 1-84 PTH assays. Changes to serum
      concentrations and relationships between these biochemical surrogate markers of
      ROD were investigated. Serum phosphate and PTH levels (measured by both assays)
      fell significantly during dialysis, whereas serum calcium, C-PTH, the 1-84 PTH: C
      PTH ratio and BALP and CTx concentrations were not significantly changed. 1-84
      PTH levels were related to pre but not post dialysis serum calcium levels and
      changes to 1-84 PTH levels during dialysis were related to changes in serum
      calcium levels. 1-84 PTH and iPTH were reduced by haemodialysis, whereas levels
      of BALP and CTx remained stable post-dialysis. The relationship between BALP and
      CTx and bone histology requires investigation to determine whether they are more
      useful markers of bone turnover in this patient group.

PMID- 17216259
TI  - Mutational analysis of NPHS2 and WT1 in frequently relapsing and steroid
      dependent nephrotic syndrome.
AB  - Idiopathic nephrotic syndrome is a common pediatric kidney disease, 80% of all
      cases are steroid sensitive (SSNS). A significant proportion of children with
      SSNS will have a frequently relapsing or steroid-dependent course (FRNS/SDNS)
      that is associated with significant treatment-related morbidity. Mutations in
      NPHS2 account for more than 28% of all cases of steroid-resistant nephrotic
      syndrome (SRNS) and dominant mutations in WT1 for 5%; while mutations are absent
      from children with uncomplicated SSNS. Since FRNS/SDNS is phenotypically
      positioned within a spectrum between SSNS and SRNS, we hypothesized that
      heterozygous mutations of NPHS2 may be causing FRNS/SDNS. Mutational analysis of
      NPHS2 and WT1 was carried out in a single-center cohort of 20 children with
      FRNS/SDNS, ten children with uncomplicated SSNS (control), and 22 children with
      SRNS (control). Renal biopsy findings were available in 15/20 children with
      FRNS/SDNS and revealed IgM nephropathy, MCNS, and FSGS in six, five, and four
      children, respectively. Children with FRNS/SDNS were significantly younger at
      first presentation than those with SSNS and SRNS (median age: 3.0 years in
      FRNS/SDNS patients, 7.0 years in SSNS patients, and 5.0 in SRNS patients; p <
      0.001). No NPHS2 or WT1 mutations were found in patients with FRNS/SDNS and
      uncomplicated SSNS. The hypothesis that FRNS/SDNS may be associated with
      heterozygous mutations in NPHS2 or WT1 was not confirmed.

PMID- 17216260
TI  - Prevention of peritonitis in children receiving peritoneal dialysis.
AB  - Peritonitis and catheter-related (exit-site/tunnel) infections are major causes
      of morbidity in children receiving peritoneal dialysis (PD). Our objective was to
      evaluate the impact of a combination of prophylactic measures on the rate of
      peritonitis and catheter-related infections subsequent to their implementation in
      2001. This is a single center review of incident patients who received automated
      peritoneal dialysis (APD) from 1997 to 2004. The causal microorganisms,
      annualized peritonitis and catheter-related infections rates and the time to
      infection were reviewed using pooled data from 1997 to 2000 and from 2001 to
      2004. Fifty-four patients received PD over 1099 patient months (pm). Twenty-eight
      peritonitis episodes occurred in 15 patients over 599 pm from 1997 to 2000
      (annualized rate (AR): 0.56 infections/patient year). Eight episodes of
      peritonitis occurred in five patients over 500 pm from 2001 to 2004 (AR: 0.19
      infections/patient year) (P = 0.01). Prior to 2001, the median time from dialysis
      initiation to the first peritonitis episode was 500 days (95% CI, 400-660 days),
      compared to 1137 days (95% CI, 1050 to +Infinity) from 2001 to 2004 (P = 0.008).
      The rate of catheter-related infections and time to initial infection during the
      two periods was not different. We conclude that measures to decrease the
      frequency of peritonitis can be successfully applied to children and should be
      incorporated as part of standard care.

PMID- 17216261
TI  - Glomerular filtration rate measurement and estimation in chronic kidney disease.
AB  - Glomerular filtration rate (GFR) assesses kidney function. GFR is measured by
      renal clearance techniques; inulin clearance is the gold standard but is not
      easily measured. Thus, other methods to determine GFR have been utilized.
      Endogenous creatinine clearance (CrCl) is the most widely used, but creatinine
      secretion falsely elevates GFR. Cimetidine inhibits creatinine secretion, such
      that CrCl equals GFR, provided there are no difficulties with bladder emptying.
      Estimation of GFR from serum creatinine (e.g. Schwartz formula) is useful
      clinically; however, such formulae have not been updated for enzymatic creatinine
      autoanalyzers. Cystatin C, a small protein, is produced at a relatively constant
      rate and is reabsorbed in the proximal tubule. Cystatin C may be more sensitive
      than creatinine in detecting a reduction in GFR, but further studies are needed
      to prove this. Single injection (plasma) clearance techniques are the most
      precise measures of GFR. Iohexol is an exogenous marker that is comparable to
      inulin and (51)Cr-EDTA and can be measured by high-performance liquid
      chromatography (HPLC). Our pilot and the Chronic Kidney Disease in Children
      (CKiD) North American studies show that iohexol can accurately measure GFR using
      a four-point plasma disappearance curve national studies show that iohexol can
      accurately measure GFR using a four-point plasma disappearance curve (10, 30,
      120, and 300 min) or, in most cases, a two-point disappearance time (120 and 300
      min).

PMID- 17216262
TI  - Pathophysiology of focal segmental glomerulosclerosis.
AB  - Focal segmental glomerulosclerosis (FSGS) is a major cause of idiopathic steroid
      resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD). In
      recent years, animal models and studies of familial forms of nephrotic syndrome
      helped elucidate some mechanisms of podocyte injury and disease progression in
      FSGS. This article reviews some of the experimental and clinical data on the
      pathophysiology of FSGS.

PMID- 17216264
TI  - Intracranial aneurysms that repeatedly reopen over time after coiling: imaging
      characteristics and treatment outcome.
AB  - INTRODUCTION: We report imaging and clinical characteristics of patients with
      aneurysms that repeatedly reopened over time and were coiled three times or more
      during a follow-up period of 2-11 years. METHODS: At angiographic follow-up of
      624 of 827 aneurysms coiled between 1995 and 2005, 74 aneurysms (8.9%) reopened
      and were additionally coiled. During an extended follow-up, 12 aneurysms (1.5%)
      in 12 patients repeatedly reopened and were repeatedly coiled. Initial aneurysm
      sizes ranged from 15 to 30 mm. Four aneurysms contained intraluminal thrombus.
      Eight aneurysms were associated with subarachnoid hemorrhage and two with a mass
      effect, and two were incidentally discovered. The locations of aneurysms were
      basilar artery (eight), carotid artery (two), anterior communicating artery (one)
      and middle cerebral artery (one). RESULTS: Altogether, 49 coil treatments were
      performed in the 12 aneurysms, ranging from three to six coil treatments per
      aneurysm. Of the 49 coil treatments, 20 (41%) were performed with a supporting
      device. There were no procedural complications (0%, 97.5% CI 0-5.7%). The mean
      clinical follow-up period was 70.6 months (median 60, range 25-135 months). All
      12 patients are neurologically doing well (GOS 5). Reopening was by compaction in
      nine aneurysms and by migration of coils into intraluminal thrombus in three
      aneurysms. In two aneurysms, late regrowth became apparent at 76 and 95 months
      after the previous coiling. CONCLUSION: Aneurysms that reopen over time and need
      to be coiled for a second time should be imaged at regular intervals to detect
      repeated reopening or regrowth. The treatment strategy of regular follow-up and
      additional treatments when necessary is effective and safe.

PMID- 17216265
TI  - Neuroradiologic characteristics of astroblastoma.
AB  - INTRODUCTION: Astroblastoma is a rare glial tumor of uncertain origin. Only a few
      scattered case reports and one small case series have described the radiologic
      appearance of this uncommon tumor. Many features previously identified are
      similar to those of other primary malignant brain tumors. We report the largest
      imaging series to date and further delineate the CT and MRI features of
      astroblastoma. We identify those features that may be useful in distinguishing
      astroblastoma from other neoplasms. METHODS: The radiologic images, pathology
      reports, and clinical information of 12 patients with pathology-confirmed
      astroblastoma were retrospectively reviewed. CT and MRI findings including
      location, morphology, signal intensity, and presence and patterns of enhancement
      were tabulated. RESULTS: Patients ranged in age from 0 (newborn) to 50 years with
      a mean of 20 years at the time of initial diagnosis. A striking female
      preponderance (11:1) was found. All tumors were supratentorial. There were
      multiple intratumoral cysts in 7 (58%) of the 12 patients. Nine (75%) showed
      strong rim enhancement and 3 (25%) showed no rim enhancement. CONCLUSION: The
      imaging features of astroblastoma are identified in 12 previously unreported
      cases. Distinguishing features that can be used to narrow the differential
      diagnosis with more common primary brain neoplasms reflect a combination of age,
      anatomic location, and specific imaging findings such as demarcation,
      heterogeneous tumor enhancement, rim enhancement, and a multicystic "bubbly"
      appearance. Intraventricular location, intratumoral hemorrhage with a fluid-fluid
      level, and dural "tails" are less common but important additions to the imaging
      spectrum.

PMID- 17216266
TI  - [Diagnosis and therapy of tumor related pain].
AB  - The World Health Organization guidelines for cancer pain therapy from 1986 are
      still valid. A prerequisite for adequate pain palliation is an exact anamnesis
      and pain diagnosis. A multimodal, staged therapeutic concept then needs to be
      formulated according to the requirements of the patient. The pharmacological
      treatment starts with non-opioids. If pain control remains insufficient, weak
      opioids are added. In case of persistent pain these are replaced by strong
      opioids. The availability of new opioids and/or preparations admits a more
      sophisticated approach to metabolic disorders and specific pain syndromes.
      Depending on the presenting pain type, co-analgesics might be added.

PMID- 17216263
TI  - Nutrition in children with CRF and on dialysis.
AB  - The objectives of this study are: (1) to understand the importance of nutrition
      in normal growth; (2) to review the methods of assessing nutritional status; (3)
      to review the dietary requirements of normal children throughout childhood,
      including protein, energy, vitamins and minerals; (4) to review recommendations
      for the nutritional requirements of children with chronic renal failure (CRF) and
      on dialysis; (5) to review reports of spontaneous nutritional intake in children
      with CRF and on dialysis; (6) to review the epidemiology of nutritional
      disturbances in renal disease, including height, weight and body composition; (7)
      to review the pathological mechanisms underlying poor appetite, abnormal
      metabolic rate and endocrine disturbances in renal disease; (8) to review the
      evidence for the benefit of dietetic input, dietary supplementation, nasogastric
      and gastrostomy feeds and intradialytic nutrition; (9) to review the effect of
      dialysis adequacy on nutrition; (10) to review the effect of nutrition on
      outcome.

PMID- 17216267
TI  - Intravitreal use of bevacizumab (Avastin) for choroidal neovascularization due to
      ARMD: a preliminary multifocal-ERG and OCT study. Multifocal-ERG after use of
      bevacizumab in ARMD.
AB  - PURPOSE: To evaluate by MFERG and OCT the macular function before and after
      intravitreal use of bevacizumab (Avastin) in eyes suffering from CNV due to ARMD.
      METHODS: Eighteen eyes with subfoveal CNV due to ARMD were studied before and
      after intravitreal use of bevacizumab with MFERG and OCT. The post treatment
      follow up was three months. RESULTS: Before treatment, OCT shows an increase of
      the retinal thickening of the fovea and the electrical response densities in the
      fovea and parafovea were decreased in all patients. Three months after treatment,
      OCT showed a real resolution of the subretinal fluid. The electrical responses in
      the fovea and parafovea remained the same or slightly improved in some cases. The
      intraocular pressure remained normal and no inflammation was observed.
      CONCLUSION: The intravitreal use of bevacizumab may provide anatomical correlates
      that support the concept of disease amelioration but the functional improvement
      of the macula three months after treatment is not obvious. However the method is
      promising and needs further evaluation.

PMID- 17216268
TI  - Conservation of large foci formation in arrested oocytes of Caenorhabditis
      nematodes.
AB  - Within the rhabditid phylogeny of nematodes, the great majority of species are
      gonochoristic, having evolved as obligate male/female species. In contrast, the
      well-studied nematode model system, Caenorhabditis elegans, is androdioecious,
      utilizing a hermaphroditic/male reproductive system. We have previously
      determined that in the arrested oocytes of old-aged C. elegans hermaphrodites
      with depleted sperm, large cytoplasmic ribonucleoprotein foci form. The formation
      of these foci is reversible, as they dissociate within 3 h after a male mates
      with the hermaphrodite, resupplying it with sperm. The functional significance of
      these oocyte foci is not known and previously has not been clear for a
      hermaphroditic species in which oocytes of young adults wait only approximately
      23 min to be fertilized. One hypothesis is that the foci function to maintain
      maternal mRNAs in oocytes while fertilization is delayed. In this paper, we
      examine four gonochoristic rhabditid species: Caenorhabditis remanei,
      Caenorhabditis sp. CB5161, Caenorhabditis sp. PS1010, and Rhabditella axei
      DF5006. We demonstrate that in three of these four species, ovulation arrests in
      unmated females until mating occurs and large cytoplasmic foci develop in
      arrested oocytes. The oocyte foci contain nuclear pore proteins and, in C.
      remanei at least, the RNA-binding protein MEX-3 as well as RNA. We speculate that
      these foci maintain the integrity of ooctyes, possibly maintaining the stability
      or translational repression of maternal mRNAs in unmated females. We further
      speculate that their presence in oocytes of old-aged C. elegans hermaphrodites is
      due to conservation from an ancestral gonochoristic state.

PMID- 17216269
TI  - RNAi-induced phenotypes suggest a novel role for a chemosensory protein CSP5 in
      the development of embryonic integument in the honeybee (Apis mellifera).
AB  - Small chemosensory proteins (CSPs) belong to a conserved, but poorly understood,
      protein family found in insects and other arthropods. They exhibit both broad and
      restricted expression patterns during development. In this paper, we used a
      combination of genome annotation, transcriptional profiling and RNA interference
      to unravel the functional significance of a honeybee gene (csp5) belonging to the
      CSP family. We show that csp5 expression resembles the maternal-zygotic pattern
      that is characterized by the initiation of transcription in the ovary and the
      replacement of maternal mRNA with embryonic mRNA. Blocking the embryonic
      expression of csp5 with double-stranded RNA causes abnormalities in all body
      parts where csp5 is highly expressed. The treated embryos show a "diffuse", often
      grotesque morphology, and the head skeleton appears to be severely affected. They
      are 'unable-to-hatch' and cannot progress to the larval stages. Our findings
      reveal a novel, essential role for this gene family and suggest that csp5 (unable
      to-hatch) is an ectodermal gene involved in embryonic integument formation. Our
      study confirms the utility of an RNAi approach to functional characterization of
      novel developmental genes uncovered by the honeybee genome project and provides a
      starting point for further studies on embryonic integument formation in this
      insect.

PMID- 17216270
TI  - Cerebellar and brainstem infarction as a complication of CT-guided transforaminal
      cervical nerve root block.
AB  - A 60-year-old man with a 4-year history of intractable neck pain and radicular
      pain in the C5 nerve root distribution presented to our department for a CT
      guided transforaminal left C5 nerve root block. He had had a similar procedure on
      the right 2 months previously, and had significant improvement of his symptoms
      with considerable pain relief. On this occasion he was again accepted for the
      procedure after the risks and potential complications had been explained. Under
      CT guidance, a 25G spinal needle was introduced and after confirmation of the
      position of the needle, steroid was injected. Immediately the patient became
      unresponsive, and later developed a MR-proven infarct affecting the left
      vertebral artery (VA) territory. This is the first report of a major complication
      of a cervical root injection under CT guidance reported in the literature. We
      present this case report and the literature review of the potential complications
      of this procedure.

PMID- 17216271
TI  - Double-bundle versus single-bundle anterior cruciate ligament reconstruction: a
      prospective, randomize clinical study.
AB  - Anatomical observation and biomechanical studies have shown that the anterior
      cruciate ligament (ACL) mainly consists of two distinct bundles, the anteromedial
      (AM) bundle and posterolateral (PL) bundle. Conventional single-bundle ACL
      reconstruction techniques have focused on the restoration of the AM bundle while
      giving limited attention to the PL bundle. The purpose of this prospective,
      randomized clinical study is to compare the outcomes of ACL reconstruction when
      using either double-bundle or single-bundle technique and bioabsorbable
      interference screw fixation, and similar rehabilitation with both techniques.
      Sixty-five patients were randomized into either double-bundle (n = 35) or single
      bundle (n = 30) ACL reconstruction with hamstring tendons and bioabsorbable screw
      (Hexalon, Inion Company, Tampere, Finland) fixation in both groups. The
      evaluation methods were clinical examination, KT-1000 arthrometer measurements,
      radiographic evaluation, as well as International Knee Documentation Committee
      and Lysholm knee scores. There were no differences between the study groups
      preoperatively. For an average of 14 months of follow-up (range 12-20 months), 30
      patients of the double-bundle group and 29 patients of the single-bundle group
      were available (91%). At the follow-up, the rotational stability, as evaluated by
      pivot shift test, was significantly better in the double-bundle group than in the
      single-bundle group. However, in anterior stability of the knee, there was no
      significant difference between the groups. None of the patients in the double
      bundle group had graft failure, while four patients in the single-bundle group
      had. In addition, knee scores were equal at the follow-up, and all the results
      were significantly better at the follow-up than preoperatively, in both groups.

PMID- 17216272
TI  - Arthroscopic or conservative treatment of degenerative medial meniscal tears: a
      prospective randomised trial.
AB  - In this prospective randomised study two treatments after non-traumatic medial
      meniscal tear diagnosed with radiological examination and magnetic resonance
      imaging were compared; arthroscopic partial meniscectomy followed by supervised
      exercise or supervised exercise alone. The aim was to evaluate knee function and
      physical activity. Ninety patients (mean age 56 years) were evaluated using the
      Knee Injury and Osteoarthritis Outcome Score, the Lysholm Knee Scoring Scale, the
      Tegner Activity Scale and a Visual Analogue Scale for knee pain prior to the
      intervention, after 8 weeks of exercise and after 6 months. According to the
      outcome scores arthroscopic partial medial meniscectomy combined with exercise
      did not lead to greater improvement than exercise alone. After the intervention
      both groups reported decreased knee pain, improved knee function and a high
      satisfaction (P<0.0001). Forty-one per cent of the patients returned to their pre
      injury activity level after 6 months. In conclusion, when evaluated with outcome
      scores, arthroscopic partial medial meniscectomy followed by supervised exercise
      was not superior to supervised exercise alone in terms of reduced knee pain,
      improved knee function and improved quality of life.

PMID- 17216273
TI  - Adipogenesis in mouse 3T3L1 cells: the effects of Rtl1 over-expression.
AB  - Rtl1 and Dlk1 are two genes in an imprinted gene cluster on mouse chromosome 12.
      Rtl1 is a paternally expressed gene encoding a retrotransposon-like protein, but
      as yet, there is no evidence that a protein is produced by this gene although a
      transcript is produced. Dlk1 is also paternally expressed and it encodes a plasma
      membrane-bound protein known to act as a negative regulator of adipogenesis.
      Genes at other imprinted loci often show coordinate expression and may interact
      at a functional level. We tested the hypothesis that Dlk1 and Rtl1 are
      functionally related. Rtl1 and Dlk1 mRNA expression patterns show similar time
      courses of down-regulation during induced adipogenesis of 3T3L1 cells. Despite
      the coordinate down-regulation of Dlk1 and Rtl1 mRNA levels, Rtl1 over-expression
      did not affect the time course of adipogenesis or Dlk1 expression. It is
      concluded that these two genes are neither directly nor indirectly functionally
      related.

PMID- 17216274
TI  - Mycorrhizal associations in woody plant species at the Mt. Usu volcano, Japan.
AB  - We investigated the association between ectomycorrhizal (ECM) and arbuscular
      mycorrhizal (AM) fungi and pioneer woody plant species in areas devastated by the
      eruption of Mt. Usu, Japan, in 2000. We observed eight woody plant species at the
      research site, most of which were associated with ECM and/or AM fungi. In
      particular, dominant woody plant species Populus maximowiczii, Salix hultenii
      var. angustifolia and Salix sachalinensis were consistently associated with ECM
      fungi and erratically associated with AM fungi. We found one to six morphotypes
      in the roots of each ECM host and, on average, two in the roots of each seedling,
      indicating low ECM fungal diversity. ECM colonization ranged from 17 to 42% of
      root tips. Using morphotyping and molecular analyses, 15 ECM fungi were
      identified. ECM fungi differed greatly between hosts. However, Laccaria
      amethystea, Hebeloma mesophaeum, Thelephora terrestris and other Thelephoraceae
      had high relative colonization, constituting the majority of the ECM colonization
      in the roots of each plant species. These ECM fungi may be important for the
      establishment of pioneer woody plant species and further revegetation at Mt. Usu
      volcano.

PMID- 17216275
TI  - Taxon-specific PCR primers to detect two inconspicuous arbuscular mycorrhizal
      fungi from temperate agricultural grassland.
AB  - Taxon-specific polymerase chain reaction (PCR) primers enable detection of
      arbuscular mycorrhizal fungi (AMF, Glomeromycota) in plant roots where the fungi
      lack discriminative morphological and biochemical characters. We designed and
      validated pairs of new PCR primers targeted to the flanking regions of the
      variable domain 1 of the nuclear ribosomal large subunit RNA gene to specifically
      detect Acaulospora paulinae and an undescribed member of the Diversisporaceae.
      These two fungal taxa, sporulating late in soil-trap cultures and showing small,
      faintly coloured spores and weakly staining intraradical structures, were
      frequently found in roots of Trifolium repens from a high-input agricultural
      grassland. The newly developed PCR primers may thus enable studies on two
      inconspicuous AMF taxa that appear to have been overlooked in previous molecular
      AMF community analyses and for which no specific PCR primers have been published.

PMID- 17216276
TI  - Involvement of reactive oxygen species during early stages of ectomycorrhiza
      establishment between Castanea sativa and Pisolithus tinctorius.
AB  - Evidence for the participation of reactive oxygen species (ROS) and antioxidant
      systems in ectomycorrhizal (ECM) establishment is lacking. In this paper, we
      evaluated ROS production and the activities of superoxide dismutase (SOD) and
      catalase (CAT) during the early contact of the ECM fungus Pisolithus tinctorius
      with the roots of Castanea sativa (chestnut tree). Roots were placed in contact
      with P. tinctorius mycelia, and ROS production was evaluated by determining the
      levels of H(2)O(2) and O(2) (.-) during the early stages of fungal contact. Three
      peaks of H(2)O(2) production were detected, the first two coinciding with O(2) (.
      ) bursts. The first H(2)O(2) production peak coincided with an increase in SOD
      activity, whereas CAT activity seemed to be implicated in H(2)O(2) scavenging. P.
      tinctorius growth was evaluated in the presence of P. tinctorius-elicited C.
      sativa crude extracts prepared during the early stages of fungal contact.
      Differential hyphal growth that matched the H(2)O(2) production profile with a
      delay was detected. The result suggests that during the early stages of ECM
      establishment, H(2)O(2) results from an inhibition of ROS-scavenging enzymes and
      plays a role in signalling during symbiotic establishment.

PMID- 17216277
TI  - PPARGC1A coding variation may initiate impaired NEFA clearance during glucose
      challenge.
AB  - AIMS/HYPOTHESIS: The peroxisome proliferator-activated receptor gamma coactivator
      1-alpha protein, encoded by the PPARGC1A gene, transcriptionally activates a
      complex pathway of lipid and glucose metabolism and is expressed primarily in
      tissues of high metabolic activity such as liver, heart and exercising oxidative
      skeletal muscle fibre. Ppargc1a-null mice develop systemic dyslipidaemia and
      hepatic steatosis. In humans, NEFAs downregulate PPARGC1A expression in skeletal
      muscle. Furthermore, a common non-synonymous coding variant at PPARGC1A
      (Gly482Ser, rs8192678) is associated with decreased PPARGC1A mRNA levels and
      increased type 2 diabetes risk. MATERIALS AND METHODS: In a population-based
      sample of 691 healthy middle-aged Europids we assessed whether Gly482Ser is
      associated with levels of NEFA when fasting and in response to an oral glucose
      challenge. We also assessed the potential effect-modifying role of adipose tissue
      mass on these phenotypes. RESULTS: After adjustment for age, sex, fat mass and
      fat-free mass, the Ser482 allele associated with higher NEFA at 30 min and 2 h
      and with NEFA AUC (all values p<or=0.02). Furthermore, suggestive evidence of
      interaction between fat mass and Gly482Ser was observed for fasting NEFA
      (p=0.059). After stratification by level of obesity, genotype associations were
      observed in the obese for fasting NEFA (p=0.028) and NEFA at 30 min (p=0.013) and
      2 h (p=0.002), and with NEFA AUC (p=0.005), but no significant associations were
      observed in lean individuals (all values p>0.6). CONCLUSIONS/INTERPRETATION: Our
      observations indicate that NEFA clearance is blunted following a glucose load in
      carriers of the PPARCG1A Ser482 allele. This association is augmented by obesity.

PMID- 17216278
TI  - The impact of glycation on apolipoprotein A-I structure and its ability to
      activate lecithin:cholesterol acyltransferase.
AB  - AIMS/HYPOTHESIS: Hyperglycaemia, one of the main features of diabetes, results in
      non-enzymatic glycation of plasma proteins, including apolipoprotein A-I (apoA
      I), the most abundant apolipoprotein in HDL. The aim of this study was to
      determine how glycation affects the structure of apoA-I and its ability to
      activate lecithin:cholesterol acyltransferase (LCAT), a key enzyme in reverse
      cholesterol transport. MATERIALS AND METHODS: Discoidal reconstituted HDL (rHDL)
      containing phosphatidylcholine and apoA-I ([A-I]rHDL) were prepared by the
      cholate dialysis method and glycated by incubation with methylglyoxal. Glycation
      of apoA-I was quantified as the reduction in detectable arginine, lysine and
      tryptophan residues. Methylglyoxal-AGE adduct formation in apoA-I was assessed by
      immunoblotting. (A-I)rHDL size and surface charge were determined by non
      denaturing gradient gel electrophoresis and agarose gel electrophoresis,
      respectively. The kinetics of the LCAT reaction was investigated by incubating
      varying concentrations of discoidal (A-I)rHDL with a constant amount of purified
      enzyme. The conformation of apoA-I was assessed by surface plasmon resonance.
      RESULTS: Methylglyoxal-mediated modifications of the arginine, lysine and
      tryptophan residues in lipid-free and lipid-associated apoA-I were time- and
      concentration-dependent. These modifications altered the conformation of apoA-I
      in regions critical for LCAT activation and lipid binding. They also decreased (A
      I)rHDL size and surface charge. The rate of LCAT-mediated cholesterol
      esterification in (A-I)rHDL varied according to the level of apoA-I glycation and
      progressively decreased as the extent of apoA-I glycation increased.
      CONCLUSIONS/INTERPRETATION: It is concluded that glycation of apoA-I may
      adversely affect reverse cholesterol transport in subjects with diabetes.

PMID- 17216280
TI  - Post-translational protein modifications in type 1 diabetes: a role for the
      repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase?
AB  - AIMS/HYPOTHESIS: Post-translational modifications, such as isomerisation of
      native proteins, may create new antigenic epitopes and play a role in the
      development of the autoimmune response. Protein-L-isoaspartate (D-aspartate) O
      methyltransferase (PIMT), encoded by the gene PCMT1, is an enzyme that recognises
      and repairs isomerised Asn and Asp residues in proteins. The aim of this study
      was to assess the role of PIMT in the development of type 1 diabetes. MATERIALS
      AND METHODS: Immunohistochemical analysis of 59 normal human tissues was
      performed with a monoclonal PIMT antibody. CGP3466B, which induces expression of
      Pcmt1, was tested on MIN6 and INS1 cells, to assess its effect on Pcmt1 mRNA and
      PIMT levels (RT-PCR and western blot) and apoptosis. Forty-five diabetes-prone
      BioBreeding (BB) Ottawa Karlsburg (OK) rats were randomised to receive 0, 14 or
      500 microg/kg (denoted as the control, low-dose and high-dose group,
      respectively) of CGP3466B from week 5 to week 20. RESULTS: A high level of PIMT
      protein was detected in beta cells. CGP3466B induced a two- to threefold increase
      in Pcmt1 mRNA levels and reduced apoptosis by 10% in MIN6 cells. No significant
      effect was seen on cytokine-induced apoptosis or PIMT protein levels in INS1
      cells. The onset of diabetes in the BB/OK rats was significantly delayed (85.6+/
      9.0 vs 84.3+/-6.8 vs 106.6+/-13.5 days, respectively; p<0.01 for high-dose vs low
      dose and control groups), the severity of the disease was reduced (glucose 22.2+/
      3.2 vs 16.9+/-2.6 vs 15.8+/-2.7 mmol; p<0.01 for high- and low-dose groups vs
      control group) and residual beta cells were more frequently identified (43% vs
      71% vs 86%; p<0.05 for high-dose vs control group) in the treated animals.
      CONCLUSIONS/INTERPRETATION: The results support a role for post-translational
      modifications and PIMT in the development of type 1 diabetes in the diabetes
      prone BB rat, and perhaps also in humans.

PMID- 17216279
TI  - Fat cell enlargement is an independent marker of insulin resistance and
      'hyperleptinaemia'.
AB  - AIMS/HYPOTHESIS: The aim of this study was to explore whether fat cell size in
      human subcutaneous and omental adipose tissue is independently related to insulin
      action and adipokine levels. MATERIALS AND METHODS: Fat cells were prepared from
      abdominal subcutaneous biopsies obtained from 49 type 2 diabetic and 83 non
      diabetic subjects and from omental biopsies obtained from 37 non-diabetic
      subjects. Cell size and insulin action on glucose uptake capacity in vitro were
      assessed in isolated fat cells. Insulin sensitivity in vivo was assessed with
      euglycaemic-hyperinsulinaemic clamps. Fasting blood samples were collected and
      adipokines and NEFA were measured. RESULTS: Negative correlations were found
      between subcutaneous fat cell size and insulin sensitivity assessed as M-value
      during clamp and as insulin action on glucose uptake in fat cells in vitro. This
      was seen in non-diabetic subjects after including age, sex and BMI in the
      analyses. No such relationship was found in type 2 diabetic subjects. In both
      groups, subcutaneous fat cell size correlated positively and independently with
      plasma levels of leptin but not to any of the other assessed adipokines. In non
      diabetic subjects, omental fat cell size was independently and negatively
      correlated with insulin action in subcutaneous, but not omental, fat cells in
      vitro. CONCLUSIONS/INTERPRETATION: Fat cell enlargement is associated with
      insulin resistance in non-diabetic individuals independently of BMI. This was not
      seen in type 2 diabetic subjects, suggesting that after development of type 2
      diabetes other factors, not related to fat cell size, become more important for
      the modulation of insulin resistance.

PMID- 17216281
TI  - Pre-eclampsia but not pregnancy-induced hypertension is a risk factor for
      diabetic nephropathy in type 1 diabetic women.
AB  - AIMS/HYPOTHESIS: Our aim was to study whether pre-eclampsia and pregnancy-induced
      hypertension are predictors of diabetic nephropathy in type 1 diabetic women.
      MATERIALS AND METHODS: A total of 203 type 1 diabetic women, who were pregnant
      between 1988 and 1996 and followed at the Department of Obstetrics and
      Gynaecology in Helsinki, were re-assessed after an average of 11 years within the
      nationwide, multi-centre Finnish Diabetic Nephropathy Study. Diabetic nephropathy
      was defined as microalbuminuria, macroalbuminuria or end-stage renal disease.
      RESULTS: Patients with prior pre-eclampsia had diabetic nephropathy more often
      than patients with a normotensive pregnancy (diabetic nephropathy vs normal
      albumin excretion rate: 41.9% vs 8.9%; p<0.001), whereas patients with a history
      of pregnancy-induced hypertension did not (10.3% vs 8.9%; p=0.81). CHD was more
      prevalent in patients with a history of pre-eclampsia than in patients with a
      normotensive pregnancy (12.2% vs. 2.2%; p=0.03). Pre-eclampsia (odds ratio [OR]
      7.7, 95% CI 1.6-36.1; p=0.01) and HbA(1c) (OR 2.0, 95% CI 1.1-3.8; p<0.05) were
      associated with incident diabetic nephropathy even when adjusted for follow-up
      time, BMI, smoking, diabetes duration and age. CONCLUSIONS/INTERPRETATION: These
      data suggest that a history of pre-eclamptic pregnancy but not pregnancy-induced
      hypertension is associated with an elevated risk of diabetic nephropathy.

PMID- 17216282
TI  - The long-term impact on offspring of exposure to hyperglycaemia in utero due to
      maternal glucokinase gene mutations.
AB  - AIMS/HYPOTHESIS: There is strong evidence that maternal diabetes while offspring
      are in utero results in offspring beta cell dysfunction and diabetes or glucose
      intolerance. Offspring born to mothers with a mutation in the glucokinase gene
      (GCK) are a good model for studying exposure to moderate hyperglycaemia, as
      mutation carriers have fasting hyperglycaemia throughout life including during
      pregnancy. We assessed the long term effects of exposure to maternal
      hyperglycaemia in utero on beta cell function and glucose tolerance in adult
      offspring. MATERIALS AND METHODS: We studied 86 adult offspring (mean age 40
      years), 49 born to glucokinase mothers (exposed to hyperglycaemia in utero) and
      37 born to glucokinase fathers (controls). We measured glucose tolerance during
      an OGTT and beta cell function using early insulin response (EIR); we also
      measured anthropometric data including birthweight. RESULTS: Offspring of
      glucokinase mothers had a higher birthweight by 450 g (p<0.001), but no evidence
      of deterioration in glucose tolerance (2-h glucose 9.1 vs 8.6 mmol/l p=0.50) or
      reduced beta cell function (log EIR 1.40 vs 1.26, p=0.11) compared with offspring
      born to glucokinase fathers. CONCLUSIONS/INTERPRETATION: The marked increase in
      birthweight shows that offspring born to affected mothers were exposed to
      increased glycaemia in utero. Despite this, there was no evidence of altered beta
      cell function or glucose tolerance. As previous human examples of marked
      programming by hyperglycaemia in utero have been in genetically predisposed
      offspring, we propose that our finding reflects the lack of genetic
      predisposition in the offspring to progressive beta cell dysfunction.

PMID- 17216283
TI  - Adiponectin receptor genes: mutation screening in syndromes of insulin resistance
      and association studies for type 2 diabetes and metabolic traits in UK
      populations.
AB  - AIMS/HYPOTHESIS: Adiponectin is an adipokine with insulin-sensitising and anti
      atherogenic properties. Several reports suggest that genetic variants in the
      adiponectin gene are associated with circulating levels of adiponectin, insulin
      sensitivity and type 2 diabetes risk. Recently two receptors for adiponectin have
      been cloned. Genetic studies have yielded conflicting results on the role of
      these genes and type 2 diabetes predisposition. In this study we aimed to
      evaluate the potential role of genetic variation in these genes in syndromes of
      severe insulin resistance, type 2 diabetes and in related metabolic traits in UK
      Europid populations. MATERIALS AND METHODS: Exons and splice junctions of the
      adiponectin receptor 1 and 2 genes (ADIPOR1; ADIPOR2) were sequenced in patients
      from our severe insulin resistance cohort (n=129). Subsequently, 24 polymorphisms
      were tested for association with type 2 diabetes in population-based type 2
      diabetes case-control studies (n=2,127) and with quantitative traits in a
      population-based longitudinal study (n=1,721). RESULTS: No missense or nonsense
      mutations in ADIPOR1 and ADIPOR2 were detected in the cohort of patients with
      severe insulin resistance. None of the 24 polymorphisms (allele frequency 2.3
      48.3%) tested was associated with type 2 diabetes in the case-control study.
      Similarly, none of the polymorphisms was associated with fasting plasma insulin,
      fasting and 2-h post-load plasma glucose, 30-min insulin increment or BMI.
      CONCLUSIONS/INTERPRETATION: Genetic variation in ADIPOR1 and ADIPOR2 is not a
      major cause of extreme insulin resistance in humans, nor does it contribute in a
      significant manner to type 2 diabetes risk and related traits in UK Europid
      populations.

PMID- 17216284
TI  - Insular carcinomas of the thyroid exhibit poor prognosis and long-term survival
      in comparison to follicular and papillary T4 carcinomas.
AB  - BACKGROUND: Insular thyroid carcinoma was described as a tumor with aggressive
      behavior, and patients usually present themselves with an advanced tumor stage.
      Whether the insular component is an independent factor for poor prognosis remains
      unclear. Therefore, in the present study, we compared the survival of patients
      with advanced insular, follicular, and papillary thyroid cancer. MATERIALS AND
      METHODS: The clinical behavior of tumors in three groups of patients with T4
      thyroid carcinoma--8 patients with insular, 11 patients with follicular, and 21
      patients with papillary thyroid carcinomas--was compared. Disease-free survival
      and disease-specific death were analyzed statistically. Cox regression analysis
      was used to evaluate the influence of histotype and other prognostic factors.
      RESULTS: At 3 years, survival was 37.5% (mean 26 months) among patients with
      insular thyroid carcinoma, 80% (mean 59 months) among those with follicular, and
      89% (mean 126 months) among those with papillary thyroid carcinomas (p = 0.007).
      Disease-free survival in patients without initial distant metastasis was worst in
      patients with insular thyroid carcinoma (20%) compared to those with follicular
      (75%) and those with papillary thyroid carcinomas (71%). CONCLUSION: Patients
      with advanced insular thyroid carcinoma have a poorer outcome in comparison to
      patients with similar advanced stage who have follicular or papillary thyroid
      carcinoma.

PMID- 17216285
TI  - Effect of pyloric drainage procedures on gastric passage and bile reflux after
      esophagectomy with gastric conduit reconstruction.
AB  - BACKGROUND AND AIMS: Controversy still exists about the need for pyloric drainage
      procedures (pyloroplasty or pyloromyotomy) after esophagectomy with
      esophagogastrostomy and vagotomy. Although pyloric drainage may prevent
      postoperative delayed gastric emptying, it may also promote bile reflux into the
      oesophagus. We analysed pyloric drainage methods for their potential effect on
      gastric outlet obstruction and bile reflux in patients undergoing esophagectomy.
      MATERIALS AND METHODS: One hundred and ninety-eight patients with esophageal
      carcinoma were treated by transthoracal esophagectomy with gastric conduit
      reconstruction either with pyloromyotomy (group II, n = 118), pyloroplasty (group
      III, n = 34) or without pyloric drainage (group I, n = 46) between January 2000
      and December 2004. The postoperative gastrointestinal passage by radiological
      investigation, anastomotic leakage rate, mortality and incidence of
      gastroesophageal reflux by endoscopy within the first postoperative year were
      retrospectively analysed. RESULTS: Patient demographics and the types of surgical
      procedures did not differ between the three groups. There was no difference in
      hospital mortality, anastomotic leakage rate, gastrointestinal passage and
      postoperative hospital stay between the three groups. However, more patients with
      pyloric drainage showed bile reflux (I = 0% vs II+III=14.9%, p = 0.069) and
      reflux esophagitis (I = 10.3% vs II+III = 34.5%, p < 0.05) compared to patients
      without pyloric drainage. On the multivariate analysis, pyloric drainage and the
      anastomotic height were independent and were significant risk factors associated
      with postoperative reflux esophagitis. CONCLUSION: Pyloric drainage after
      esophagectomy with gastric conduit reconstruction should be omitted because it
      does not improve gastric emptying and may favour biliary reflux esophagitis.

PMID- 17216287
TI  - QSAR models for predicting the activity of non-peptide luteinizing hormone
      releasing hormone (LHRH) antagonists derived from erythromycin A using quantum
      chemical properties.
AB  - Multiple linear regression (MLR) combined with genetic algorithm (GA) and
      Bayesian-regularized Genetic Neural Networks (BRGNNs) were used to model the
      binding affinity (pK(I)) of 38 11,12-cyclic carbamate derivatives of 6-O
      methylerythromycin A for the Human Luteinizing Hormone-Releasing Hormone (LHRH)
      receptor using quantum chemical descriptors. A multiparametric MLR equation with
      good statistical quality was obtained that describes the features relevant for
      antagonistic activity when the substituent at the position 3 of the erythronolide
      core was varied. In addition, four-descriptor linear and nonlinear models were
      established for the whole dataset. Such models showed high statistical quality.
      However, the BRGNN model was better than the linear model according to the
      external validation process. In general, our linear and nonlinear models reveal
      that the binding affinity of the compounds studied for the LHRH receptor is
      modulated by electron-related terms.

PMID- 17216286
TI  - Quantum chemical study of the mechanism of ethylene elimination in silylative
      coupling of olefins.
AB  - Silylative coupling of olefins differs from olefin metathesis. Although in both
      these reactions ruthenium catalysts play a crucial role and ethylene product is
      detected, ruthenium-carbene intermediate is formed only in the course of the
      metathesis reaction. In this study quantum chemical calculations based on the
      density functional theory (DFT) have been carried out in order to examine the
      mechanism of the silylative coupling of olefins leading to ethylene elimination.
      In the first step of the catalytic cycle, a hydrogen atom from the ruthenium
      catalytic center is transferred preferentially to the carbon atom bound to Si in
      a vinylsilane. This H transfer is coupled with the formation of Ru-C bond. Next,
      the rotation around the newly formed C-C single bond occurs so that silicon atom
      is placed in the vicinity of the ruthenium center. The following step involves
      the migration of a silyl moiety, and leads to Ru-Si bond formation, coupled with
      ethylene elimination. The next reaction, that is the insertion of ethylene
      (alkene) into Ru-Si bond, has an activation barrier almost as high as the
      reaction of ethylene elimination. However, the posibility of removing gaseous
      ethylene from the reactive mixture together with the entropic fators suggests
      that the insertion of alkene that is larger than C(2)H(4) is the rate limiting
      step in the silylative coupling of olefins. It also suggests that the
      substituents attached to the silicon atom or the carbon atoms of an alkene by
      electronic and steric effects may significantly affect silyl migration and thus
      the effectiveness of the catalytic reaction.

PMID- 17216288
TI  - Differential involvement of 3', 5'-cyclic adenosine monophosphate-dependent
      protein kinase in regulation of Fos and tyrosine hydroxylase expression in the
      heart after naloxone induced morphine withdrawal.
AB  - We previously demonstrated that morphine withdrawal induced hyperactivity of the
      heart by the activation of noradrenergic pathways innervating the left and right
      ventricle, as evaluated by noradrenaline (NA) turnover and Fos expression. We
      investigated whether cAMP-dependent protein kinase (PKA) plays a role in this
      process by estimating changes in PKA immunoreactivity and the influence of
      inhibitor of PKA on Fos protein expression, tyrosine hydroxylase (TH)
      immunoreactivity levels and NA turnover in the left and right ventricle.
      Dependence on morphine was induced by a 7-day s.c. implantation of morphine
      pellets. Morphine withdrawal was precipitated on day 8 by an injection of
      naloxone (5 mg/kg). When opioid withdrawal was precipitated, an increase in PKA
      immunoreactivity and phospho-CREB (cyclic AMP response element protein) levels
      were observed in the heart. Moreover, morphine withdrawal induces Fos expression,
      an enhancement of NA turnover and an increase in the total TH levels. When the
      selective PKA inhibitor HA-1004 was infused, concomitantly with morphine pellets,
      it diminished the increase in NA turnover and the total TH levels observed in
      morphine-withdrawn rats. However, this inhibitor neither modifies the morphine
      withdrawal induced Fos expression nor the increase of nonphosphorylated TH
      levels. The present findings indicate that an up-regulated PKA-dependent
      transduction pathway might contribute to the activation of the cardiac
      catecholaminergic neurons in response to morphine withdrawal and suggest that Fos
      is not a target of PKA at heart levels.

PMID- 17216290
TI  - Nicotinic acetylcholine receptors: targets for commercially important
      insecticides.
AB  - Nicotinic acetylcholine receptors (nAChRs) are major excitatory neurotransmitter
      receptors in both vertebrates and invertebrates. In insects, nAChRs are the
      target site for several naturally occurring and synthetic compounds that exhibit
      potent insecticidal activity. Several compounds isolated from plants are potent
      agonists or antagonists of nAChRs, suggesting that these may have evolved as a
      defence mechanism against insects and other herbivores. Nicotine, isolated from
      the tobacco plant, has insecticidal activity and has been used extensively as a
      commercial insecticide. Spinosad, a naturally occurring mixture of two
      macrocyclic lactones isolated from the microorganism Saccharopolyspora spinosa,
      acts upon nAChRs and has been developed as a commercial insecticide. Since the
      early 1990s, one of the most widely used and rapidly growing classes of
      insecticides has been the neonicotinoids. Neonicotinoid insecticides are potent
      selective agonists of insect nAChRs and are used extensively in both crop
      protection and animal health applications. As with other classes of insecticides,
      there is growing evidence for the evolution of resistance to insecticides that
      act on nAChRs.

PMID- 17216291
TI  - Detection and quantification of hepatitis B virus DNA by SYBR green real-time
      polymerase chain reaction.
AB  - A single-round real-time polymerase chain reaction (PCR) assay based on SYBR
      green dye technology for the detection and quantification of hepatitis B virus
      (HBV) DNA in serum was evaluated and compared with a qualitative nested PCR and
      the Cobas Amplicor HBV Monitor assay (Roche Molecular Diagnostics, Milan, Italy).
      The performance of the real-time PCR assay was evaluated in a routine clinical
      laboratory setting with a total of 212 clinical specimens. The sensitivity of the
      real-time PCR corresponded to 31 IU/ml (70 copies/ml), and comparison with the
      qualitative nested PCR showed significant concordance for 94% of samples. The
      linear curve over 7 log units, spanning 10(3)-10(9) IU/ml (2.28 x 10(3) to 2.28 x
      10(9) copies/ml), was observed in the quantitative determination. The
      interexperimental variability coefficient of the assay ranged from 0.22 to 0.39
      and the intraexperimental variability coefficient from 0.24 to 0.41. By excluding
      values outside of the dynamic ranges of both tests, the HBV Monitor and the real
      time PCR gave an agreement within +/-1 log unit for 90% of samples, while those
      for the remaining 10% were found to be above 1 log unit but less than 1.5 log
      units. When the results inside and outside the dynamic range of the HBV Monitor
      were examined, 90% of the results were in agreement. In conclusion, the real-time
      PCR based on SYBR green technology proved suitable for routine diagnostic
      purposes, showing good sensitivity, high specificity, high reproducibility, and
      good linearity over a broad dynamic range of quantification.

PMID- 17216293
TI  - Piriformis muscle: clinical anatomy and consideration of the piriformis syndrome.
AB  - Patients with lumbosacral and buttock pain provide tacit support for recognizing
      the piriformis muscle as a contributing factor to the pain (piriformis syndrome).
      One hundred and twelve cadaveric specimens were observed to elucidate the
      anatomical variations of the piriformis muscle referred to the diagnostic and
      treatment of the piriformis syndrome. The distance between the musculotendinous
      junction and the insertion was measured and the piriformis categorized into three
      types: Type A (71, 63.39%): long upper and short lower muscle belly; Type B (40,
      35.71%): short upper and long lower muscle belly; Type C (1, 0.9%): fusion of
      both muscle bellies at the same level. The diameter of the piriformis tendon at
      the level of the musculotendinous junction ranged from 3 to 9 mm (mean: 6.3 mm).
      The piriformis showed the following possible fusions with adjacent tendons. In
      type one (60, 53.57%) a rounded tendon of the piriformis reached the upper border
      of the greater trochanter. In type two (33, 29.46%) it first joined into the
      gemellus superior tendon and at last both fused with the obturator internus
      tendon and inserted into the medial surface of the greater trochanter. A fusion
      of the piriformis, obturator internus and gluteus medius tendon with the same
      insertion area as above was observed in type three (15, 13.39%) and finally in
      type four (4, 3.57%) the tendon fused with the gluteus medius to reach the upper
      surface of the greater trochanter. Based on this survey anatomical causes for the
      piriformis syndrome are rare and a more precise workup is necessary to rule out
      more common diagnosis.

PMID- 17216294
TI  - Assessment of cup position from plain radiographs: impact of pelvic tilting.
AB  - The acetabular cup position after total hip arthroplasty (THA) regarding its
      inclination and version angles are influential parameters concerning the
      postoperative range of motion and dislocation stability. Standard anterior
      posterior X-rays remain an important diagnostic instrument to observe the
      postoperative outcome and to secure quality control after THA, where an optimal
      positioning of the patient is recommended when taking these X-rays. The purpose
      of this preliminary study was to determine the effect of pelvic tilting regarding
      the positioning calculation of the acetabular cup from standard radiographs using
      a modified method according to Pettersson et al. (Acta Radiol Diagn, 23:259-263,
      1982). In our model experiment, we were able to show that pelvic tilting to
      either side causes a considerable difference between the radiographic and
      calculated version angles following approximately linear functions. However,
      pelvic tilting to either side, leads, regarding the calculation of the
      inclination, to an average deviation between radiographic and calculated
      inclination angles less than 2 degrees .

PMID- 17216296
TI  - Effect of phosphate binders upon TSH and L-thyroxine dose in patients on thyroid
      replacement.
AB  - BACKGROUND: While calcium carbonate is known to interfere with the
      gastrointestinal absorption of levothyroxine, we hypothesized that other
      phosphate binders would also bind to levothyroxine and decrease bioavailability
      of levothyroxine in dialysis patients. METHODS: The records of 1,566 patients on
      hemodialysis who were being treated by the Hypertension, Nephrology, Dialysis,
      and Transplantation Center (the regional renal referral center for Eastern
      Alabama, USA) were evaluated. The type of phosphate binder and amount were then
      correlated (two-tailed Pearson Correlation) to TSH levels, serum phosphorus and
      the amount of levothyroxine taken. Friedman Test and Wilcoxon Signed Ranks Test
      were performed to analyze the significance of difference in thyroxine dosing and
      TSH levels between the different phosphate binders. RESULTS: Sixty-seven patients
      were identified who were taking levothyroxine while taking three different kinds
      of phosphate binders; namely, calcium carbonate, calcium acetate, and sevelamer
      HCl. We found that the TSH levels of patients on calcium carbonate (P = 0.002)
      and sevelamer HCl (P = 0.033) were significantly higher than patients on calcium
      acetate with the difference increasing with time on each binder. Sevelamer was
      also found to be associated with significantly higher dosing requirement of
      thyroid replacement than those on either calcium carbonate or calcium acetate (Z
      = -3.17, P = 0.001). CONCLUSION: Sevelamer (but not calcium acetate) in addition
      to calcium carbonate appears to interfere with the bioavailability of
      levothyroxine.

PMID- 17216295
TI  - The impact of informing psychiatric patients about their medication: a systematic
      review.
AB  - AIM: This literature study explores the impact of educational interventions about
      medicines for psychiatric patients on adherence, knowledge and economic, clinical
      and humanistic outcomes. METHOD: A systematic review of eight electronic
      databases was carried out. Reference lists of primary studies were searched.
      Studies measuring the impact of medication information for adult psychiatric
      patients in an individual way on adherence, knowledge, economic, clinical and
      humanistic outcomes were included. Data analysis and assessment of methodological
      quality were executed according to the Cochrane Collaboration guidelines. A meta
      analysis of primary studies was not suitable due to the heterogeneity of the
      primary studies. RESULTS: Literature search generated 17 studies. Thirteen
      studies measured adherence, seven of which reported an increase. Generally,
      adherence was 11-30% higher in the intervention groups than in the control group.
      A combination of oral and written information seemed to have an added value as
      compared with supplying exclusively oral or written information. The provision of
      easily readable written information improved adherence by 11%. Seven of the eight
      studies measuring knowledge reported an overall improvement. Knowledge was
      increased with 14-28% in interventions groups in comparison with control group.
      One study reported an increased satisfaction. No significant differences were
      seen for frequency of side-effects, relapse or admission rates, symptoms and
      quality of life. Not one of the 17 studies explored the economic impact of the
      educational intervention. The methodological quality of the included studies was
      variable. Individual studies suffered from a variety of biases and other
      methodological limitations. CONCLUSION: The included studies suggested a positive
      impact on adherence and knowledge. As only one study assessed patient's
      satisfaction, no definitive conclusions can be made. No significant differences
      were observed for frequency of side-effects, relapse or admission rates, symptoms
      and quality of life. Studies on the cost-effectiveness of such interventions need
      to be performed. In general, more well-designed studies with good methodological
      quality in this research domain are needed.

PMID- 17216297
TI  - Risk of tuberculosis in dialysis patients: association of tuberculin and 2,4
      dinitrochlorobenzene reactivity with risk of tuberculosis.
AB  - BACKGROUND: Dialysis patients are at increased risk of tuberculosis (TB) and
      anergy due to attenuated cellular immunity. AIM: To define specific risks of TB
      in anergic and non-anergic dialysis patients. METHODS: A total of 272 dialysis
      patients were enrolled in this prospective study over a 36-month follow-up.
      Entering the study, participants had Mantoux and 2,4-dinitrochlorobenzene skin
      tests and their cell-mediated immunity (CMI)-index was estimated. Patients were
      classified as anergic (CMI-index<or=2 and Mantoux<or=4 mm) or non-anergic.
      Specific relative risks of TB were then calculated, using data from both the
      general population and 49 non-uremic health care workers. The independent effect
      of sex, age and diabetes mellitus was determined using Cox's proportional hazard
      method. RESULTS: Among the 116 (42.6%) anergics 13 (11.2%), and among the 156 non
      anergics 11 (7%) developed active tuberculosis. Anergics had a significantly
      higher risk of TB than non-anergics (Adjusted Relative Risks, 98.3, 95% CI 58.65
      113.6 versus 61.6, 95% CI 13.6-72.1, P=0.003). Tuberculin reactivity was weakly
      associated with the subsequent risk of TB (r=0.51). The latter showed a steadily
      decreasing trend with increasing CMI-index (r=-0.99). CONCLUSION: Anergy distorts
      the association of tuberculin reactivity with risk of TB. Anergic dialysis
      patients are at increased risk of developing active TB and chemoprophylaxis is
      justified in them too.

PMID- 17216298
TI  - Transglucosylation of ascorbic acid to ascorbic acid 2-glucoside by a recombinant
      sucrose phosphorylase from Bifidobacterium longum.
AB  - A novel transglycosylation reaction from sucrose to L-ascorbic acid by a
      recombinant sucrose phosphorylase from Bifidobacterium longum was used to produce
      a stable L-ascorbic acid derivative. The major product was detected by HPLC, and
      confirmed to be 2-O-alpha-D-glucopyranosyl-L-ascorbic acid by LC-MS/MS analysis.

PMID- 17216299
TI  - Production of herbicide-resistant sweet potato plants transformed with the bar
      gene.
AB  - Herbicide-resistant sweet potato plants were produced through biolistics of
      embryogenic calli derived from shoot apical meristems. Plant materials were
      bombarded with the vectors containing the beta-glucuronidase gene (gusA) and the
      herbicide-resistant gene (bar). Selection was carried out using phosphinothricin
      (PPT). Transformants were screened by the histochemical GUS and Chlorophenol Red
      assays. PCR and Southern-blot analyses indicated the presence of introduced bar
      gene in the genomic DNA of the transgenic plants. When sprayed with Basta, the
      transgenic sweet potato plants was tolerant to the herbicide. Hence, we report
      successful transformation of the bar gene conferring herbicide resistance to
      sweet potato.

PMID- 17216300
TI  - Amyloglucosidase-catalyzed synthesis of eugenyl and curcuminyl glycosides.
AB  - Glycosylation of the phenolic hydroxyl group of the phenyl propanoid systems,
      eugenol 1 and curcumin 2, using an amyloglucosidase from Rhizopus and a beta
      glucosidase from sweet almonds together with carbohydrates (D-glucose 3, D
      mannose 4, maltose 5, sucrose 6 and D-mannitol 7) in di-isopropyl ether produced
      glycosides at 7-52% yields in 72 h. Spectral studies indicated that the reaction
      occurred between the phenolic OH groups and C-1 and/or 6-O-groups of the
      carbohydrates with curcumin exhibiting bis glycosylation.

PMID- 17216301
TI  - Production, formulation and antagonistic activity of the biocontrol like-yeast
      Aureobasidium pullulans against Penicillium expansum.
AB  - Aureobasidium pullulans (de Bary) Arnaud (Ach 1-1) was grown in a glucose fed
      batch fermentor to 106 g dry wt l(-1) in 48 h. The cells were dried in a
      fluidized bed dryer with a final viability of 62%. After 7 months at 4 degrees C,
      the viability was 28% of the initial value (= 2.3 x 10(10 )c.f.u. g(-1) dry
      matter). A protection level of 89% was achieved with the biomass preparation at 1
      x 10(8 )c.f.u. ml(-1) after 28 and 7 days for apples stored respectively at 5 and
      25 degrees C against Penicillium expansum. Our process is suitable to produce
      large quantities of the strain Ach 1-1 as biological control agent for apple
      preservation.

PMID- 17216302
TI  - Pyridoxal 5'-phosphate may be curative in early-onset epileptic encephalopathy.
AB  - Neonatal epileptic encephalopathy can be caused by inborn errors of metabolism.
      These conditions are often unresponsive to treatment with conventional
      antiepileptic drugs. Six children with pyridox(am)ine-5'-phosphate oxidase (PNPO)
      deficiency presented with neonatal epileptic encephalopathy. Two were treated
      with pyridoxal 5'-phosphate (PLP) within the first month of life and showed
      normal development or moderate psychomotor retardation thereafter. Four children
      with late or no treatment died or showed severe mental handicap. All of the
      children showed atypical biochemical findings. Prompt treatment with PLP in all
      neonates and infants with epileptic encephalopathy should become mandatory,
      permitting normal development in at least some of those affected with PNPO
      deficiency.

PMID- 17216303
TI  - Fluorescent in situ hybridization on tissue microarrays: challenges and
      solutions.
AB  - Tissue microarray (TMA) technology has provided a high throughput means of
      evaluating potential biomarkers and therapeutic targets in archival pathological
      specimens. TMAs facilitate the rapid assessment of molecular alterations in
      hundreds of different tumours on a single slide. Sections from TMAs can be used
      for any in situ tissue analysis, including fluorescent in situ hybridization
      (FISH). FISH is a molecular technique that detects numerical and structural
      abnormalities in both metaphase chromosomes and interphase nuclei. FISH is
      commonly used as a prognostic and diagnostic tool for the detection of
      translocations and for the assessment of gene deletion and amplification in
      tumours. Performing FISH on TMAs enables researchers to determine the clinical
      significance of specific genetic alterations in hundreds of highly characterized
      tumours. The use of FISH on archival paraffin embedded tissues is technically
      demanding and becomes even more challenging when applied to paraffin embedded
      TMAs. The problems encountered with FISH on TMAs, including probe preparation,
      hybridization, and potential applications of FISH, will be addressed in this
      review.

PMID- 17216304
TI  - Three-dimensional experiment for solid-state NMR of aligned protein samples in
      high field magnets.
AB  - A pulse sequence that yields three-dimensional (1)H chemical shift/(1)H-(15)N
      heteronuclear dipolar coupling/(15)N chemical shift solid-state NMR spectra is
      demonstrated on a uniformly (15)N labeled membrane protein in magnetically
      aligned phospholipid bilayers. Based on SAMPI4, the pulse sequence yields high
      resolution in all three dimensions at a (1)H resonance frequency of 900 MHz with
      the relatively low rf field strength (33 kHz) available for a lossy aqueous
      sample with a commercial spectrometer and probe. The (1)H chemical shift
      frequency dimension is shown to select among amide resonances, which will be
      useful in studies of larger polytopic membrane proteins where the resonances
      overlap in two-dimensional spectra. Moreover, the (1)H chemical shift, which can
      be measured from these spectra, provides an additional orientationally dependent
      frequency as input for structure calculations.

PMID- 17216306
TI  - Comparison of plasma metabolite concentrations and lactate dehydrogenase activity
      in dogs, cats, horses, cattle and sheep.

PMID- 17216305
TI  - Adaptation of a velogenic Newcastle disease virus to vero cells: assessing the
      molecular changes before and after adaptation.
AB  - A velogenic Newcastle disease virus isolate was passaged 50 times in Vero cell
      culture and the virus was assessed for the molecular changes associated with the
      passaging. At every 10th passage, the virus was characterized conventionally by
      mean death time (MDT) analysis, intracerebral pathogenicity index (ICPI) and
      virus titration. At increasing passage levels, a gradual reduction in the
      virulence of the virus was observed. Molecular characterization of the virus
      included cloning and sequencing of a portion of the fusion gene (1349 bp)
      encompassing the fusion protein cleavage site (FPCS), which was previously
      amplified by reverse transcription-polymerase chain reaction. Sequence analysis
      revealed a total of 135 nucleotide substitutions which resulted in the change of
      42 amino acids between the velogenic virus and the 50th passage virus. The
      predicted amino acid motif present at the cleavage site of the virulent virus was
      (109)SRRRRQRRFVG(119) and the corresponding region of the adapted adapted virus
      was (109)SGGRRQKRFIG(119). Pathogenicity studies conducted in 20-week-old
      seronegative birds revealed gross lesions such as petechial haemorrhages in the
      trachea, proventricular junction and intestines, and histopathological changes
      such as depletion and necrosis of the lymphocytes in thymus, spleen, bursa and
      caecal tonsils in the birds injected with the velogenic virus and absence of the
      lesions in birds injected with the adapted virus. The 50th-passage cell culture
      virus was back-passaged five times in susceptible chickens and subjected to
      virulence attribute analysis and sequence analysis of the FPCS region, with minor
      difference found between them.

PMID- 17216307
TI  - Efficiency of feeding Duddingtonia flagrans chlamydospores to control nematode
      parasites of first-season grazing goats in France.
AB  - A field trial, conducted over two consecutive years, was aimed at assessing the
      efficacy of the administration of spores of the nematophagous fungus Duddingtonia
      flagrans to young goats for the control of nematode parasite infections on a
      French commercial dairy goat flock. For both years, the first-year grazing kids
      were divided into two similarly managed groups (fungus and control groups): in
      2003 a daily dose rate of 5 x 10(5) spores/kg body weight was given to the fungus
      group animals, while in 2004 a daily dose rate of 10(6) spores/kg body weight was
      used; the other half of the kids, acting as control, did not receive the spores.
      Parameters measured every 3 weeks included nematode egg excretion, larval
      development in faecal cultures and pasture larval counts. Additionally, at the
      beginning, the middle and the end of each grazing season, the goats were weighed
      and blood samples for pepsinogen determination were collected. In 2003, similar
      results were recorded for all the measured parameters in the control and fungus
      groups. In contrast, in 2004, the kids receiving the spores showed lower faecal
      egg counts and pepsinogen levels at the end of the season and higher growth rate
      compared to kids of the control group.

PMID- 17216308
TI  - Disposition kinetics of difloxacin after intravenous, intramuscular and
      subcutaneous administration in calves.
AB  - The pharmacokinetics of difloxacin (Dicural) was studied in a crossover study
      using three groups (n = 4) of male and female Friesian calves after intravenous
      (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administrations of 5 mg/kg
      body weight. Drug concentration in plasma was determined by high-performance
      liquid chromatography using fluorescence detection. The plasma concentration-time
      data following i.v. administration were best fitted to a two-compartment open
      model and those following i.m. and s.c. routes were best fitted using one
      compartment open model. The collected data were subjected to a computerized
      kinetic analysis. The mean i.v., i.m. and s.c. elimination half-lives
      (t(1/2beta)) were 5.56 +/- 0.33 h, 6.12 +/- 0.42 h and 7.26 +/- 0.6 h,
      respectively. The steady-state volume of distribution (V(dss)) was 1.12 +/- 0.09
      L/kg and total body clearance (Cl(B)) was 2.19 +/- 0.1 ml/(min x kg). The
      absorption half lives (t(1/2ab)) were 0.38 +/- 0.027 h and 2.1 +/- 0.09 h, with
      systemic bioavailabilities (F) of 96.5% +/- 6.4% and 84% +/- 5.5% after i.m. and
      s.c. administration, respectively. After i.m. and s.c. dosing, peak plasma
      concentrations (C(max)) of 3.38 +/- 0.13 microg/ml and 2.18 +/- 0.12 microg/ml
      were attained after (t(max)) 1.22 +/- 0.20 h and 3.7 +/- 0.52 h. The MIC90 of
      difloxacin for Mannheimia haemolytica was 0.29 +/- 0.04 microg/ml. The AUC/MIC90
      and C(max)/MIC90 ratios for difloxacin following i.m. administration were 120 and
      11.65, respectively and following s.c. administration were 97.58 and 7.51,
      respectively. Difloxacin was 31.7-36.8% bound to calf plasma protein. Since
      fluoroquinolones display concentration-dependent activities, the doses of
      difloxacin used in this study are likely to involve better pharmacodynamic
      characteristics that are associated with greater clinical efficacy following i.m.
      administration than following s.c. administration.

PMID- 17216309
TI  - Experimental infection of pigs with 'Candidatus Helicobacter suis'.
AB  - 'Candidatus Helicobacter suis' is a spiral-shaped bacterium that colonizes the
      stomach of more than 60% of slaughter pigs. The role of 'Candidatus Helicobacter
      suis' in gastric disease of pigs is still unclear. Experimental studies in pigs
      are lacking because this bacterium is unculturable until now. An inoculation
      protocol using 'Candidatus Helicobacter suis' infected mouse stomach homogenate
      was used to reproduce the infection in pigs. Control animals were inoculated
      using negative mouse stomach homogenate. Pigs were inoculated three times with
      one-week intervals and euthanized 6 weeks post inoculation. Tissue samples were
      taken from different mucosal stomach regions to detect 'Candidatus Helicobacter
      suis' by PCR and urease test. Mucosal inflammation was evaluated on formalin
      fixed tissue samples. Lesions in the pars oesophagea were scored macroscopically.
      Infection was successful in all challenged animals, with the antrum and the
      fundus being predominantly positive. Infection was associated with infiltration
      of lymphocytes and plasma cells in the antral mucosa, evolving to follicular
      gastritis. No apparent inflammation of the fundic stomach region was detected in
      the infected animals. A clear link between 'Candidatus Helicobacter suis' and
      pars oesophageal lesions could not be found.

PMID- 17216310
TI  - Development of an indirect ELISA for the detection of antibodies against Peste
      des-petits-ruminants virus in small ruminants.
AB  - Peste des petits ruminants (PPR) is an acute, febrile, highly contagious and
      economically important viral disease of small ruminants. A polyclonal antibody
      based indirect ELISA was developed for detection of antibodies to PPR virus in
      the serum samples of goats and sheep using purified PPR viral antigen propagated
      in Vero cell culture. A threshold (cut-off) value was set as twice the mean of
      the negative population based on the distribution of known negative serum samples
      in respect of PPR virus antibodies in the test. A total of 1544 serum samples
      from goats and sheep were screened by indirect ELISA and competitive ELISA. The
      indirect ELISA compared very well with competitive ELISA, with a high degree of
      specificity (95.09%) and sensitivity (90.81%). When compared with virus
      neutralization test, the present assay had 100% specificity and 80% sensitivity.
      With serum samples, the assay could clearly differentiate animals from the
      infected population from uninfected ones. These results suggest that the indirect
      ELISA may be a good alternative tool to competitive ELISA for seroepidemiological
      surveys.

PMID- 17216311
TI  - Successful treatment of canine open cervix-pyometra with Yun-Nan-Pai-Yao, a
      Chinese herbal preparation.

PMID- 17216312
TI  - Anatomy of the thoracic splanchnic nerves in pigs.
AB  - The anatomical features of the autonomous nerves, including the greater, lesser
      and least splanchnic nerves, were examined in 4 female and 4 male adult pigs (Sus
      scrofa). The origin and course of these nerves were examined with regard to sex
      and the side of the body. The greater splanchnic nerve was present in all of the
      animals included in the study, whereas the lesser splanchnic nerve was present at
      a rate of 87.5% on the right side and 75% on the left side of the median plane.
      On the other hand, the least splanchnic nerve was present on the right side at a
      rate of 62.5% and on the left side at a rate of 37.5%. The greater, lesser and
      least splanchnic nerves on the right side of the median plane were determined to
      originate from a more cranial location. Furthermore, these nerves were observed
      to be longer and larger on the right side in comparison with the left side.
      Evaluation of the findings revealed no significant difference between both sides
      of the median plane with regard to the origin, course and dimensions of these
      nerves. Similarly, no significant difference was detected between sexes.

PMID- 17216313
TI  - Potential aflatoxin and ochratoxin a production by Aspergillus species in poultry
      feed processing.
AB  - Poultry feeds are prone to fungal growth and mycotoxin production during
      processing. The identification of biota with the ability to produce mycotoxins is
      essential. The aims of this study were (1) to monitor the mycobiota counts at
      different stages of poultry feed processing; (2) to determine the occurrence of
      Aspergillus species; (3) to evaluate the natural incidence of aflatoxins and
      ochratoxin A. The ability of Aspergillus spp. and its teleomorphs isolated here
      to produce these toxins was also investigated. Samples (144) were collected at
      random from a factory in Brazil. The occurrence of Aspergillus and Eurotium
      species was demonstrated on DRBC and DG18 media and the production of aflatoxins
      and ochratoxin A and their natural incidence were determined by TLC and HPLC
      methods. A. flavus and E. chevalieri were the most prevalent species isolated.
      Fungal contamination was not found after the pelleting process, though
      Aspergillus and Eurotium species were recovered from trough samples. High levels
      of aflatoxin and ochratoxin A producers were found at all stages of poultry feed
      processing. Also, high natural contamination with aflatoxins and ochratoxin A was
      found in the samples. Contact of feed with remainder poultry feed could lead to
      fungal contamination, so the risk of aflatoxin and/or ochratoxin A contamination
      of feed must be taken into account.

PMID- 17216314
TI  - Metabolism of methenolone acetate in a veal calf.
AB  - The use of anabolic steroids has been banned in the European Union since 1981. In
      this study, the metabolism of the anabolic steroid methenolone acetate, was
      investigated in a male veal calf. After daily oral administration of methenolone
      acetate, three main metabolites were detected in both urine and faeces samples.
      Among these metabolites, alpha-methenolone was apparently the main one, but 1
      methyl-5alpha-androstan-3,17-diol and 3alpha-hydroxy-1-methyl-5alpha-androstan-17
      one were also observed. The parent compound was still detectable in faeces. As a
      consequence, abuse of methenolone acetate as growth promoter can be monitored by
      analysing urine and faeces samples. A few days after the last treatment, however,
      no metabolites were observed. Alpha-methenolone was detectable in urine until 5
      days after the last treatment, but in faeces no metabolites were detectable after
      3 days.

PMID- 17216315
TI  - Stimulation of the in vitro migration of ovine eosinophils by factors derived
      from the sheep scab mite, Psoroptes ovis.
AB  - The ectoparasitic astigmatid mite Psoroptes ovis causes sheep scab, a highly
      contagious, severe allergic dermatitis associated with damage to the fleece and
      hide, loss of condition and occasional mortality. The scab lesion is
      characterized by a massive infiltration of eosinophils that begins very rapidly
      after infection. This paper reports the finding that mite-derived factors
      directly enhance the migration of ovine eosinophils in vitro. Significant (p <
      0.01) and dose-dependent (r = 0.972 +/- 0.018 (SD)) activity was initially
      identified in whole mite extracts, by comparison with medium controls in an assay
      based on modified Boyden chambers and ovine bone marrow target cells. Similar pro
      migratory activity (p < 0.005; r = 0.928 +/- 0.069 (SD)) was detected in washes
      containing mite excretory/secretory material. By direct comparison with migration
      ratios (n = 3) for defined chemotactic (rmeotaxin = 3.430 +/- 0.360 (SD)) and
      chemokinetic (rminterleukin-5 = 0.982 +/- 0.112 (SD)) stimuli it was determined
      that the activity in both mite extracts (0.992 +/- 0.038 (SD)) and mite washes
      (0.969 +/- 0.071 (SD)) was chemokinetic. Subsequent experiments (n = 3) in which
      live mites were incorporated directly into the in vitro assay system indicated
      that they produced factors that significantly (p < 0.001) enhanced eosinophil
      migration to a degree directly related to mite numbers (r = 0.993 +/- 0.005
      (SD)). The identity of the factor(s) responsible is uncertain, but their presence
      suggests that mites may be capable of directly activating eosinophils in vivo,
      and raises the possibility that mites could directly influence, perhaps even
      initiate, the rapid early tissue eosinophilic response observed in experimental
      sheep scab infections.

PMID- 17216316
TI  - Immunopathology of Dirofilaria immitis infection.
AB  - Heartworm disease caused by Dirofilaria immitis affects canine and feline hosts,
      with infections occasionally being reported in humans. Studies have shown that
      both dirofilarial antigens and those derived from its bacterial endosymbiont
      Wolbachia, interact with the host organism during canine, feline and human
      infections and participate in the development of the pathology and in the
      regulation of the host's immune response. Both innate and acquired immune
      responses are observed and the development of the acquired response may depend on
      the host and, or on its parasitological status. This review aims at illustrating
      current research on the role of both D. immitis and Wolbachia, in the immunology
      and immunopathology of dirofilariosis.

PMID- 17216317
TI  - Cloning and characterization of type 4 fimbrial gene (ptfA) of Pasteurella
      multocida serogroup B:2 (strain P52).

PMID- 17216318
TI  - Effects of epidural ketamine-xylazine combination on the clinicophysiological and
      haematobiochemical parameters of uraemic and healthy goats.
AB  - Xylazine-ketamine combination was evaluated for its efficacy and safety after
      epidural administration in uraemic and healthy goats. The combination (xylazine
      0.025 mg/kg and ketamine 2.5 mg/kg) was administered to uraemic (n = 6) and
      healthy (n = 6) animals in the lumbosacral epidural space. The combination was
      evaluated in terms of clinical, physiological, haematological and biochemical
      parameters. The onset of analgesia was faster in healthy animals than in uraemic
      animals. Xylazine and ketamine produced complete analgesia of tail, perineum,
      inguinal and thigh regions in all animals of both groups. However, healthy
      animals showed longer duration of complete analgesia than did uraemic animals.
      Greater ataxia was recorded in healthy animals than in uraemic animals. The heart
      rate showed a significant decrease in both groups; however, respiratory rate and
      rectal temperature did not show any significant changes. Haemoglobin, packed cell
      volume and total leukocyte count decreased non-significantly in both groups.
      Total leukocyte count was significantly higher in uraemic animals. A
      significantly higher value of urea nitrogen and creatinine was recorded in
      uraemic animals. The blood electrolytes (Na+, K+ and Cl-) and blood gases (PO2
      and PCO2) did not show any significant changes in both groups; however, base
      excess was significantly higher in uraemic animals. The effects produced by the
      combination on different systems were transient and values normal as the effect
      of the drugs wore off. The results suggest that the combination when used
      epidurally in uraemic goats produced effective and safe surgical analgesia.

PMID- 17216319
TI  - The effects of cytopathic and noncytopathic bovine viral diarrhoea virus with
      sperm cells on in vitro fertilization of bovine oocytes.

PMID- 17216320
TI  - Bacteriocin activity of enterococci from rabbits.
AB  - The antimicrobial spectrum of bacteriocin-producing enterococcal isolates from
      rabbits faeces, the biochemical characterization of bacteriocins, and their
      molecular mass and the presence of structural genes for bacteriocin production
      were investigated. Among enterococci selected from rabbit faeces, six strains of
      Enterococcus faecium (EF2019, EF1819, EF2119, EF1839, EF529, EF24/10) showed
      inhibitory activity against the indicators E. avium EA5, Listeria innocua
      LMG13568 and Listeria monocytogenes CCM4699 and against other enterococci and
      staphylococci tested. The molecular mass of bacteriocin-like substances ranged
      from 3 to 10 kDa. The presence of the structural genes for enterocins (ent) A, P
      and L50B was detected in all enterococci tested. However, no strain possessed the
      gene for ent B. E. faecium EF2019 showed the broadest inhibitory activity. A
      proteinaceous substance produced by the EF2019 strain was partially purified.
      This is a thermostable substance that is stable at pH 4.0, 7.0 and 9.0. Its
      production starts in the early logarithmic growth phase and culminates in the
      late logarithmic growth phase of the EF2019 strain. Partially purified
      bacteriocin (PPB) EF2019 added to the growing strain L. innocua LMG13568 (after 4
      h) inhibited its growth as early as 1 h after addition with a decrease of 1.5 log
      cycles (5 h of cultivation). This effect was extended up to 24 h. The
      bacteriocinogenic E. faecium EF2019 strain and/or bacteriocin EF2019 could be
      utilized against contaminant bacteria, e.g. in rabbitries. More detailed studies
      under in vitro and in vivo conditions are in progress.

PMID- 17216321
TI  - Plasma concentration of insulin-like growth factor I (IGF-I) in growing Ardenner
      horses suffering from juvenile digital degenerative osteoarthropathy.
AB  - Degenerative osteoarthropathy resulting in a reduced active lifespan was observed
      in Ardenner horses. In the context of joint biology, insulin-like growth factor I
      (IGF-I) is a potential candidate to affect the anabolism of cartilage matrix
      molecules. A group of 30 Ardenner horses reared under standardized conditions
      from weaning were evaluated periodically from 15 to 28 months of age to detect
      the early manifestations of the disease. At the end of this period, horses were
      classified in two pathological groups related to the degree of interphalangeal
      degenerative osteoarthropathy based on clinical and radiographic evaluations:
      healthy (46.7%) and pathological (53.3%) horses. Seven sequential blood samples
      were taken from each horse (during the evaluation period) to study the variation
      of IGF-I plasma concentration. We tested the variations of the IGF-I plasma
      concentration during growth, and the effect of sex and of pathological classes.
      Significant variations were observed during the research period, with a maximum
      value corresponding to spring and a minimum in autumn. A significant reduction of
      the IGF-I plasma concentration was also observed in the pathological horses
      (433.5 +/- 19.5 ng/ml) compared to the healthy horses (493.9 +/- 18.2 ng/ml). An
      alteration in the level of this growth factor could induce a disregulation of the
      mechanisms involved in the local control of joint and bone tissue development.

PMID- 17216323
TI  - Hypotension induced by lateral decubitus or supine spinal anaesthesia in elderly
      with low ejection fraction undergone hip surgery.
AB  - OBJECTIVE: The aim of the study was to assess the effect of low ejection fraction
      (EF) on hypotension during lateral or supine position of spinal anaesthesia in
      patients older than 75 years old. METHODS: We analyzed 41 patients who had
      undergone hip surgery between August 2000 and October 2001 in the Aydin SSK State
      Hospital retrospectively. Patients older than 75 years of age and an EF less than
      50% were selected and spinal anaesthesia was performed with hyperbaric
      bupivacaine 0.5%, lateral decubitus or supine position. The patients were divided
      into two groups: Group I (unilateral group, n = 23) and Group II (supine group, n
      = 18). History of hypertension, diabetes mellitus, and ASA status, preoperative
      value of EF and cardiac index, and intraoperative hypotension, bradycardia,
      ephedrine use, and maximal sensorial block levels were recorded. RESULTS: The age
      range of patients was between 75 and 103. The maximal sensorial block level was
      evaluated due to lower or higher than thoracic sixth segment for each patient in
      intraoperative period. The sensorial block level higher than thoracic sixth
      segment were determined 2 patient in Group I and 14 patients in Group II (p =
      0.001). Hypotension was observed in five patients in Group I and 10 patients in
      Group II (p = 0.015). In Group I, the number of ephedrine used patient was lower
      than Group II (p = 0.015). CONCLUSIONS: Elderly patients with low EF were more
      likely to predispose to higher sensorial block level and hypotension was more
      common during spinal anaesthesia with supine position compared to lateral
      decubitus position.

PMID- 17216322
TI  - The effects of the extent of spinal block on the BIS score and regional cerebral
      oxygen saturation in elderly patients: A prospective, randomized, and double
      blinded study.
AB  - BACKGROUND: Patients may become sedated with spinal anesthesia; however, the
      effect of the extent of spinal block on the Bispectral index (BIS), a processed
      electroencephalographic variable, has not been fully investigated. We evaluated
      the influence of the extent of spinal block on BIS values and on regional
      cerebral oxygen saturation (rSO(2)) in elderly patients. METHODS: A prospective,
      randomized, double-blinded study was performed in 55 ASA II patients undergoing
      urological surgery. The patients were randomly allocated into one of two groups
      to receive 2.7 ml of 0.5% hyperbaric bupivacaine or 1.5 ml, and then divided into
      two groups according to level of spinal blockade: high spinal group (Th6 and
      above) or low spinal group (Th12 and below). Systolic blood pressure (SBP), heart
      rate (HR), cardiac output (CO), stroke volume (SV), BIS values, and rSO(2) were
      measured for 30 min. CO and SV were evaluated using impedance cardiograph
      methods. RESULTS: The level of spinal blockade was Th4.7 +/- 1.0 in high spinal
      group (n = 20) and L2.5 +/- 2.2 in low spinal group (n = 20). High spinal
      anesthesia produced a significant decrease in SBP (p < 0.01) and SV (p < 0.01),
      but had no effect on CO. High spinal anesthesia significantly decreased BIS
      values (p < 0.01) without affecting rSO(2). There was relationship between level
      of spinal blockade and BIS values (r = 0.566). In contrast, no changes in above
      parameters were found in low spinal group. CONCLUSIONS: This study provides
      evidence that the extent of spinal block may have significant influence on BIS
      values without affecting rSO(2) in elderly patients.

PMID- 17216324
TI  - Prostatic fatty acids and cancer recurrence after radical prostatectomy for early
      stage prostate cancer.
AB  - OBJECTIVE: Results from some observational studies suggest that diet and energy
      balance influence the clinical course of early-stage prostate cancer. To evaluate
      possible mechanisms, we prospectively examined the relation between prostatic
      concentrations of fatty acids at diagnosis and cancer recurrence following
      primary therapy. METHODS: Fatty acids were measured by capillary gas
      chromatography in fresh, non-cancerous prostate tissue collected from 184 men
      undergoing radical prostatectomy for clinically localized prostate cancer. Their
      association with risk of biochemical disease recurrence (a rising serum prostate
      specific antigen following a disease-free [<0.1 ng/ml] interval > or =6 months)
      was analyzed using Cox proportional hazards models incorporating patient age,
      body mass index, tumor characteristics at diagnosis, and ethnicity. RESULTS:
      During an average follow-up of 48.7 months (median = 47), 14 patients experienced
      biochemical recurrence. Percent total polyunsaturated fatty acid and the ratio of
      oleic-to-stearic acid associated with risk (multivariable hazards ratio [HR] =
      0.51, 95% confidence interval [CI] = 0.29 to 0.90, p = 0.021 and HR = 1.68, 95%
      CI = 1.21 to 2.33, p = 0.002, respectively, per 1 standard deviation increase).
      CONCLUSIONS: The results of this study are preliminary, but they suggest that pre
      diagnostic prostatic concentrations of fatty acids associate with risk of
      biochemical recurrence following radical prostatectomy for clinically localized
      prostate cancer.

PMID- 17216325
TI  - Estimating age-specific breast cancer risks: a descriptive tool to identify age
      interactions.
AB  - OBJECTIVE: Clarifying age-specific female breast cancer risks and interactions
      may provide important etiologic clues. METHOD: Using a population-based case
      control study in Poland (2000-2003) of 2,386 incident breast cancer cases and
      2,502 control subjects aged 25-74 years, we estimated age-specific breast cancer
      incidence rates according to risk factors. RESULTS: Breast cancer risks were
      elevated among women with positive family history (FH), younger age at menarche,
      older age at first full-term birth, nulliparity, exogenous hormonal usage, and
      reduced physical activity (PA). Notwithstanding overall risks, we observed
      statistically significant quantitative (non-crossover) and qualitative
      (crossover) age interactions for all risk factors except for FH and PA. For
      example, nulliparity compared to parity reduced breast cancer risk among women
      ages 25-39 years then rates crossed or reversed, after which nulliparity
      increased relative risks among women ages 40-74 years. CONCLUSION: Though
      quantitative age interactions could be expected, qualitative interactions were
      somewhat counterintuitive. If confirmed in other populations, qualitative
      interactions for a continuous covariate such as age will be difficult to
      reconcile in a sequential (multistep or monolithic) 'stochastic' breast cancer
      model. Alternatively, the reversal of relative risks among younger and older
      women suggests subgroup heterogeneity with different etiologic mechanisms for
      early-onset and late-onset breast cancer types.

PMID- 17216326
TI  - Microreview: capsule-associated genes of Cryptococcus neoformans.
AB  - Cryptococcosis, caused by Cryptococcus neoformans is a common systemic mycosis in
      man and animals, particularly immunocompromised patients. This pathogenic fungus
      produces a thick extracellular polysaccharide capsule. Four capsule-associated
      genes (CAP10, CAP59, CAP60, CAP64) were cloned and sequenced, and proved to be
      essential for capsule synthesis. However biochemical functions of CAP gene
      products have not been clarified yet. Recently, the relatedness of the
      polysaccharide capsule and four capsule-associated genes has partly been
      elucidated. Nucleotide sequence of four CAP gene fragments was analyzed for
      phylogenetic relationships, and they were in agreement with the conventional
      classification of varieties and serotypes within C. neoformans. Expression of
      four CAP genes and capsule size were examined using two media containing
      different amount of glucose, and the results indicated that CAP genes might play
      important roles in elaboration of extracellular polysaccharide capsule.
      Furthermore, analyses of CAP genes in various clinical samples would give the
      useful information to diagnose cryptococcosis in human and animals.

PMID- 17216327
TI  - Modeling competition for infection sites on roots by nonpathogenic strains of
      Fusarium oxysporum.
AB  - By use of plane and solid geometry and probability models, efficiencies of
      infection and competition for nutrients and infection sites by a nonpathogenic
      strain of Fusarium oxysporum (C14) with F. oxysporum f. sp. cucumerinum on the
      rhizoplane of cucumber were calculated. The model is derived from previously
      published data. Efficiencies for successful infection were 0.04 chlamydospores
      per infection site for both pathogen and nonpathogen. Observed successful
      infections by the pathogen in competition with the nonpathogen were close in
      values to the competition ratio (CR) calculated as the number of chlamydospores
      on the infection court of the pathogen divided by the total number of both
      pathogen and nonpathogen at relatively low densities. When total chlamydospores
      were, on average, closer than 175 microm apart, however, competition for
      nutrients/mutual inhibition occurred. At such densities there was an
      overestimation of the effect of competition for infection sites. These
      relationships were modeled at inoculum densities of pathogen and/or nonpathogen
      of 5000 chlamydospores per g soil and above, however, in the field, maximum
      densities of 1000 colony forming units/g (cfu) were observed. Most likely models
      of competition for infection sites at this density of the pathogen revealed that
      infection efficiency was only approximately halved, even when 0.98 of the
      possible 30 infection sites were occupied by the nonpathogen. It is conclude that
      competition for nutrients and/or infection sites is an insignificant factor in
      biocontrol of Fusarium wilt diseases by nonpathogenic fusaria.

PMID- 17216328
TI  - Ochratoxin A and citrinin nephrotoxicity in New Zealand White rabbits: an
      ultrastructural assessment.
AB  - In the present investigation, ochratoxin A (OTA) (0.75 mg/kg feed) and citrinin
      (CIT) (15 mg/kg feed) were fed alone and in combination to young growing New
      Zealand White rabbits for 60 days to evaluate renal ultrastructural alterations.
      The severity and intensity of renal ultrastructural changes varied with the type
      of the treatment, and predominant and consistent lesions were recorded in the
      proximal convoluted tubule (PCT) lining cells. The significant changes in
      mitochondria, the most affected cell organelle in all the treatment groups,
      included mitochondrial disintegration and distortion, pleomorphism, cluster
      formation and misshapen appearance such as signet ring, dumbbell, cup and U
      shapes. Intra-cisternal sequestrations of involuting mitochondria, and thickening
      of basal layer of PCT epithelial cells with partial detachment, were the
      characteristic features observed in OTA and combination treatments. CIT treatment
      revealed crenated nucleus, loss of nucleolus, depletion of cytoplasmic
      organelles, mitochondrial pleomorphism, nuclear fragmentation, uniform folding of
      cell membrane and cytoplasmic vacuolations in the PCTs. Focal thickening of the
      glomerular basement membrane and degeneration of endothelial cells were the
      prominent alterations in the glomeruli in OTA and combination treatments. Distal
      convoluted tubules were unaffected in CIT treatment, however, mild to moderate
      lesions were observed in OTA and combination treated rabbits. It may be concluded
      that on simultaneous exposure, CIT potentiated the toxic effects of OTA on renal
      ultrastructure.

PMID- 17216329
TI  - Biodiversity of Fusarium species in Mexico associated with ear rot in maize, and
      their identification using a phylogenetic approach.
AB  - Fusarium proliferatum, F. subglutinans, and F. verticillioides are known causes
      of ear and kernel rot in maize worldwide. In Mexico, only F. verticillioides and
      F. subglutinans, have been reported previously as causal agents of this disease.
      However, Fusarium isolates with different morphological characteristics to the
      species that are known to cause this disease were obtained in the Highland-Valley
      region of this country from symptomatic and symptomless ears of native and
      commercial maize genotypes. Moreover, while the morphological studies were not
      sufficient to identify the correct taxonomic position at the species level,
      analyses based in the Internal Transcribed Spacer region and the Nuclear Large
      Subunit Ribosomal partial sequences allowed for the identification of F.
      subglutinans, F. solani, and F. verticillioides, as well as four species (F.
      chlamydosporum, F. napiforme, F. poae, and F. pseudonygamai) that had not
      previously been reported to be associated with ear rot. In addition, F. napiforme
      and F. solani were absent from symptomless kernels. Phylogenetic analysis showed
      genetic changes in F. napiforme, and F. pseudonygamai isolates because they were
      not true clones, and probably constitute separate sibling species. The results of
      this study suggest that the biodiversity of Fusarium species involved in ear rot
      in Mexico is greater than that reported previously in other places in the world.
      This new knowledge will permit a better understanding of the relationship between
      all the species involved in ear rot disease and their relationship with maize.

PMID- 17216330
TI  - Outbreaks of phaeohyphomycosis in the chinook salmon (Oncorhynchus tshawytscha)
      caused by Phoma herbarum.
AB  - Phoma herbarum has been associated with two outbreaks of systemic mycosis in
      hatchery-reared chinook salmon (Oncorhynchus tshawytscha) fingerlings. Affected
      fish exhibited abnormal swimming behavior, exophthalmia, multiple rounded areas
      of muscle softening, protruded hemorrhagic vents, and abdominal swelling. In all
      affected fish, swimbladders were filled with whitish creamy viscous fungal mass,
      surrounded by dark red areas in swimbladder walls, kidneys, and musculature.
      Clinical and histopathological examinations suggest that the infection may have
      started primarily in the swimbladder and then spread to the kidneys,
      gastrointestinal tract, and surrounding musculature. Consistent microscopical
      findings included broad septate branched fungal hyaline hyphae, 5-12 microm in
      diameter within the swimbladder, stomach, and often within and adjacent to blood
      vessels. Profuse growths of woolly brown fungal colonies were obtained from
      swimbladders and kidneys on Sabouraud medium. On corn meal agar the formation of
      pycnidia, characteristic of Phoma spp., was detected within 10 days of
      incubation. Morphological and molecular analyses identified this fungus as Phoma
      herbarum. This report underscores systemic fungal infections as a threat to
      raceway-raised salmon.

PMID- 17216331
TI  - In vitro antagonism of Thielaviopsis paradoxa by Trichoderma longibrachiatum.
AB  - Seventy-nine Trichoderma strains were isolated from soil taken from 28 commercial
      plantations of Agave tequilana cv. 'Azul' in the State of Jalisco, Mexico. Nine
      of these isolates produced nonvolatile metabolites that completely inhibited the
      growth of Thielaviopsis paradoxa on potato dextrose agar plates. These isolates
      were identified as Trichoderma longibrachiatum on the basis of their morphology
      and DNA sequence analysis of two genes (ITS rDNA and translation elongation
      factor EF-1alpha). Mycoparasitism of Th. paradoxa by T. longibrachiatum strains
      in dual cultures was examined by scanning electron microscopy. The Trichoderma
      hyphae grew alongside the Th. paradoxa hyphae, but penetration of Thielaviopsis
      hyphae by Trichoderma was no apparent. Aleurioconidia of Th. paradoxa were
      parasitized by Trichoderma. Both hyphae and aleurioconidia of Th. paradoxa lost
      turgor pressure, wrinkled, collapsed and finally disintegrated. In liquid
      cultures, all nine Trichoderma isolates produced proteases, beta-1,3-glucanases
      and chitinases that would be responsible for the degradation of Thielaviopsis
      hyphae. These results demonstrate that the modes of action of T. longibrachiatum
      involved against Th. paradoxa in vitro experiments are mycoparasitism and the
      production of nonvolatile toxic metabolites.

PMID- 17216332
TI  - Response to joint attention in toddlers at risk for autism spectrum disorder: a
      prospective study.
AB  - Response to joint attention (RJA) is impaired in preschoolers with autism
      spectrum disorder (ASD) and is pivotal to social and communication development.
      Response to joint attention was examined at 14 and 24 months in 51 children at
      high risk for autism (siblings of children with autism). Outcome groups at age 3
      years included ASD (n = 16), broader autism phenotype (n = 8), and non-broader
      autism phenotype (n = 27). The ASD group made minimal improvement in RJA between
      14 and 24 months, but stability of RJA across tasks increased for all three
      groups. Significantly, lower RJA was observed for the ASD group at 24 months.
      Response to joint attention performance at 14 months predicted ASD outcome.
      Response to joint attention is an important screening and early intervention
      target.

PMID- 17216333
TI  - Sex differences in toddlers with autism spectrum disorders.
AB  - Although autism spectrum disorders (ASD) prevalence is higher in males than
      females, few studies address sex differences in developmental functioning or
      clinical manifestations. Participants in this study of sex differences in
      developmental profiles and clinical symptoms were 22 girls and 68 boys with ASD
      (mean age = 28 months). All children achieved strongest performance in visual
      reception and fine motor followed by gross motor and language functioning. Sex
      differences emerged in developmental profiles. Controlling for language, girls
      achieved higher visual reception scores than boys; boys attained higher language
      and motor scores and higher social-competence ratings than girls, particularly
      when controlling for visual reception. Longitudinal, representative studies are
      needed to elucidate the developmental and etiological significance of the
      observed sex differences.

PMID- 17216334
TI  - A model for adapting evidence-based behavioral interventions to a new culture:
      HIV prevention for psychiatric patients in Rio de Janeiro, Brazil.
AB  - As in other countries worldwide, adults with severe mental illness in Brazil have
      elevated rates of HIV infection relative to the general population. However, no
      HIV prevention interventions have been tested for efficacy with psychiatric
      patients in Brazil. We conducted participatory research with local providers,
      community leaders, patient advocates, and patients using an intervention
      adaptation process designed to balance fidelity to efficacious interventions
      developed elsewhere with fit to a new context and culture. Our process for
      adapting these interventions comprised four steps: (1) optimizing fidelity; (2)
      optimizing fit; (3) balancing fidelity and fit; and (4) pilot testing and
      refining the intervention. This paper describes how these steps were carried out
      to produce a Brazilian HIV prevention intervention for people with severe mental
      illness. Our process may serve as a model for adapting existing efficacious
      interventions to new groups and cultures, whether at a local, national, or
      international level.

PMID- 17216335
TI  - Luminal stimuli acutely sensitize visceromotor responses to distension of the rat
      stomach.
AB  - Inflammation can enhance responses to different stimuli consistent with the
      development of hypersensitivity. To determine whether sequentially applied
      stimuli interact, we determined visceromotor responses (VMR) to gastric
      distension, measured at baseline and 60 min after instillation of saline,
      glycocholic acid (GCA) or ethanol through a gastrostomy in controls and rats with
      gastric ulcers. In another series of experiments, chemicals were administered
      before and 60 min after repeated distension of the stomach. Ethanol, but not
      saline or GCA, increased VMR in controls with a more significant rise in rats
      with gastric ulcerations. GCA increased responses to gastric distension in
      controls, whereas GCA and ethanol enhanced responses to gastric distensions in
      rats with gastric ulcers. Responses to saline, GCA, or ethanol were not affected
      by repeated noxious distension of the stomach. Luminal stimuli can trigger
      visceromotor responses and sensitize gastric afferents to mechanical stimulation,
      thus potentially contributing to dyspeptic symptoms.

PMID- 17216336
TI  - A randomized, double-blind, one-week study comparing effects of a novel COX-2
      inhibitor and naproxen on the gastric mucosa.
AB  - CS-706 is a novel cyclooxygenase-2 (COX-2) inhibitor with potent analgesic, anti
      inflammatory, and antitumor properties in animal models. This one-week,
      multicenter study was undertaken to assess the safety and tolerability of CS-706
      and to compare the effects of CS-706 versus naproxen on acute gastrointestinal
      (GI) mucosal injury. Healthy men and women (n=160) without evidence of underlying
      gastroduodenal lesions were randomized to placebo, 100 mg CS-706 once daily, 200
      mg CS-706 once daily, or 500 mg naproxen twice daily, administered for 7 days. On
      Day 8, subjects underwent a posttreatment upper GI endoscopy to assess
      development of gastroduodenal petechiae, erosions, and ulcers. Inhibition of COX
      1 and COX-2 activity over the 24-hr postdose interval on Day 7 was determined in
      48 subjects (12 per treatment group). CS-706 was safe and well tolerated. The
      extent of upper GI mucosal injury for both CS-706 dose groups was statistically
      significantly less than that for naproxen (P < 0.001) and was similar to placebo
      (P=0.615 and P=0.115 for 100 and 200 mg CS-706, respectively). No subject in
      placebo or either CS-706 treatment group had gastroduodenal ulcers, compared with
      11 (28.2%) subjects treated with naproxen (P < 0.001). Both doses of CS-706
      inhibited COX-2 activity to a similar extent as naproxen, whereas neither dose of
      CS-706 showed meaningful inhibition of platelet COX-1. In contrast, naproxen
      nearly completely inhibited COX-1 over the dosing interval. We conclude that CS
      706, dosed up to 200 mg once daily, has an acute, upper GI toxicity profile
      similar to that of placebo and significantly superior to that of naproxen.

PMID- 17216337
TI  - Bioavailability of a novel, water-soluble vitamin E formulation in malabsorbing
      patients.
AB  - In cystic fibrosis (CF), pancreatic insufficiency and a diminished bile acid pool
      cause malabsorption of important nutrients and dietary components leading to
      deficiency, poor nutritional status, and oxidative stress. Of particular
      significance is the malabsorption of fat-soluble nutrients and antioxidants,
      which are important for normal immune and neurologic function. Patients with CF
      often are deficient in these compounds despite supplementation with the current
      standard of care therapy. The objective was to compare the pharmacokinetic
      profile of this water-soluble vitamin E formulation (Aqua-E) with an oil-based
      softgel formulation in a malabsorbing patient population. Patients with CF who
      had documented malabsorption were recruited for participation in this
      pharmacokinetic study. Patients who met inclusion and exclusion criteria
      discontinued vitamin E supplementation, except for that in a multivitamin, for 7
      to 21 days before the day of dosing. Patients were randomized to a single dose of
      20 ml of Aqua-E or three oil-based softgels, which contained equivalent amounts
      of tocopherols. Blood was drawn from patients at time 0, 2, 4, 8, 24, 48, and 168
      hr and analyzed for tocopherols. Eight patients were enrolled in the study and
      randomized to Aqua-E or softgels. The primary outcome, the absorption of gamma
      tocopherol in Aqua-E (AUC=115 micro g/ml(*)hr), was significantly greater than
      that of oil-based softgels (AUC=25.3 micro g/ml(*)hr; P=0.013). Total-tocopherols
      (alpha+gamma+delta) in Aqua-E (AUC=294 micro g/ml(*)hr) showed a strong trend
      toward increased absorption compared with that of oil-based softgels (AUC=117
      micro g/ml(*)hr; P=0.09). In conclusion, this novel, water-soluble formulation
      showed a marked and statistically significant increase in absorption of gamma
      tocopherol in malabsorbing patients with CF compared with an oil-based
      formulation.

PMID- 17216338
TI  - Colonic lymphoid aggregates in slow transit constipation.
AB  - Information available on colonic lymphoid aggregates, apart from data of patients
      with inflammatory conditions, is scarce in other pathologic conditions. We
      investigated colonic lymphoid aggregates in patients with severe slow transit
      constipation, unresponsive to conventional therapeutic measures, and undergoing
      surgery for relief of their symptoms. Tissues from 27 patients with intractable
      slow transit constipation were obtained and compared with 10 controls. The
      number, diameter, lymphocyte distribution, and proliferative index were
      calculated and compared in both groups. Constipated patients displayed a
      significantly increased number of colonic lymphoid aggregates compared with
      controls. No differences were found concerning the other variables. The increase
      of colonic lymphoid aggregates found in severely constipated patients may
      represent a protective mucosal mechanism toward the chronic fecal stasis.

PMID- 17216339
TI  - CD4+ CD25+ FoxP3+ T-cell infiltration and heme oxygenase-1 expression correlate
      with tumor grade in human gliomas.
AB  - Regulatory T-cells play an important role in the regulation of the immune
      response and the mediation of dominant immunologic tolerance. We have previously
      shown that these cells are elevated in tumors and blood of patients with
      glioblastoma multiforme. Heme oxygenase-1, a rate-limiting enzyme in heme
      catabolism, has also been shown to accumulate during glioma progression and to
      play a critical role in FoxP3 mediated immune suppression. In this study, we
      investigated the correlation between FoxP3 and HO-1 expression in patients with
      various grades of astrocytoma (WHO grade II-IV). Using qualitative and
      quantitative reverse transcriptase-polymerase chain reaction and quantitative
      flow cytometry analyses, we analyzed FoxP3 and HO-1 expression in 19 patients
      with different grades of astrocytoma. We observed the highest level of FoxP3
      expression in patients with grade IV tumors (11.54 +/- 1.95%) vs. grade III (6.74
      +/- 0.19%) or grade II (2.53 +/- 0.11%) (P < 0.05). Moreover, in grade IV tumors,
      the frequency of HO-1 mRNA expression in CD4+ CD25+ cells was 11.8 +/- 2.45% vs.
      7.42 +/- 0.31% in grade III and 2.33 +/- 0.12% in grade II. Tumor infiltrating
      Treg stained positively with anti-HO-1 antibody. The expression of HO-1
      correlated with CD4+ CD25+ FoxP3+ infiltration (r = 0.966). Our results confirm
      that HO-1 expressing Treg accumulate during glioma progression. This study also
      suggests that HO-1 mRNA expression is linked to the induction of Foxp3 in CD4+
      CD25+ glioma infiltrating Treg. These findings support the suppressive role
      played by regulatory T-cells in the growth of malignant brain tumors.

PMID- 17216340
TI  - Alteration of serum and tumoral neural cell adhesion molecule (NCAM) isoforms in
      patients with brain tumors.
AB  - The neural cell adhesion molecule (NCAM) is involved in the intercellular
      junctions of neurons and glial cells. We investigated its relevance as a
      biomarker in gliomas which main characteristic is their high invasiveness. We
      studied by Western blot the pattern of serum NCAM bands in patients with gliomas
      (n = 34), with brain metastasis of different primary cancers (n = 27) and with
      benign brain tumors (n = 22)] compared with healthy controls (n = 69). For
      densitometric analysis NCAM bands > or = 130 kDa (HMW) and <130 kDa (LMW) were
      clustered. We observed that glioma patients presented higher NCAM HMW and lower
      NCAM LMW levels than control subjects (P < 0.01). A similar pattern was found in
      patients with brain metastasis or brain benign tumors, suggesting that the
      pattern of serum NCAM bands would be useful to detect brain tumor pathology. On
      the other hand, serum NCAM expression was not associated with the main
      clinicopathological features of gliomas, including overall survival.
      Interestingly, we found that 9/12 patients with glioma showed a significant
      decrease in NCAM HMW/LMW ratio between 1-3 months after successful tumor removal.
      Thus, serum NCAM could be a useful marker for monitoring treatment.NCAM
      expression was also analyzed at tissular level in 59 glioma sections from
      paraffined tumors. We observed that NCAM immunostaining was inversely correlated
      with the histological grade of malignancy, remaining this association in a
      multivariate analysis. Besides, loss of NCAM staining was significantly
      associated with bad prognosis in an univariate analysis.

PMID- 17216342
TI  - Family based association analyses between the serotonin transporter gene
      polymorphism (5-HTTLPR) and neuroticism, anxiety and depression.
AB  - We studied the association between the short/long promotor-based length
      polymorphism of the serotonin transporter gene (5-HTTLPR) and neuroticism,
      anxiety and depression. Subjects included twins, their siblings and parents from
      the Netherlands Twin Register (559 parents and 1,245 offspring). Subjects had
      participated between one and five times in a survey study measuring neuroticism,
      anxiety and depression. Offspring of these families were also approached to
      participate in a psychiatric interview diagnosing DSM-IV major depression. Within
      family and total association between 5-HTTLPR and these traits were tested. Only
      three of the 36 tests showed a significant effect of 5-HTTLPR (P<0.05). These
      effects were in opposite directions, i.e. both negative and positive regression
      coefficients were found for the s allele. No additive effect of the s allele was
      found for DSM-IV depression. Our results strongly suggest that there is no
      straightforward association between 5-HTTLPR and neuroticism, anxiety and
      depression.

PMID- 17216341
TI  - Personal digital assistants are comparable to traditional diaries for dietary
      self-monitoring during a weight loss program.
AB  - Dietary self-monitoring is considered the core of behavioral weight control
      programs. As software for personal digital assistants (PDA) has become more
      available, this study investigated whether the use of a PDA would improve dietary
      self-monitoring frequency and subsequent weight loss over the use of traditional
      paper diaries. One-hundred-seventy-six adults (BMI 25-39.9) participated in a 6
      month behavioral weight control program. Treatment subjects (n = 61) were
      provided with a PalmZire 21 with Calorie King's Diet Diary software installed.
      Their self-monitoring habits and weight loss were compared with the results from
      a previous program (n = 115) which followed the same protocol using paper diaries
      for self-monitoring. No significant differences in weight loss or dietary self
      monitoring were found. More frequent self-monitoring correlated with weight loss
      in both groups (p<.001). People seeking to lose weight should be encouraged to
      self-monitor and be matched with a mode of self-monitoring that is fitting to
      their lifestyle and skills.

PMID- 17216343
TI  - A study of how socioeconomic status moderates the relationship between SNPs
      encompassing BDNF and ADHD symptom counts in ADHD families.
AB  - Recent animal research suggests that brain-derived neurotrophic factor (BDNF),
      may mediate response to different environmental stimuli. In this paper, we
      evaluated the possible role of BDNF as a moderator of attention deficit
      hyperactivity disorder (ADHD) in the context of different socioeconomic classes.
      We genotyped ten single nucleotide polymorphisms (SNPs) in and around BDNF in 229
      families and evaluate whether there are SNP-by-socioeconomic status (SES)
      interactions for attention deficit hyperactivity. We developed three quantitative
      phenotypes for ADHD from nine inattentive and nine hyperactive-impulsive symptoms
      that were used in SNP-by-SES interaction analyses using a new methodology
      implemented in the computer program PBAT. Findings were adjusted for multiple
      comparisons using the false discovery rate. We found multiple significant SNP-by
      SES interactions using the inattentive symptom count. This study suggests that
      different SES classes may modify the effect of the functional variant(s) in and
      around BDNF to have an impact on the number of ADHD symptom counts that are
      observed. The two exons within BDNF represent potential functional variants that
      may be causing the observed associations.

PMID- 17216345
TI  - A difficult decision.

PMID- 17216344
TI  - Patterns of psychopathology in the families of children with conduct problems,
      depression, and both psychiatric conditions.
AB  - Comorbid conduct problems (CPs) and depression are observed far more often than
      expected by chance, which is perplexing given minimal symptom overlap. In this
      study, relations between parental psychopathology and children's diagnostic
      status were evaluated to test competing theories of comorbidity. Participants
      included 180 families with an 8-12-year-old child diagnosed with CPs, depression,
      both conditions, or neither condition. Although no single theory of comorbidity
      was supported fully, evidence suggested that CPs and depression may be inherited
      separately. Paternal antisocial characteristics and maternal depression provided
      independent prediction of both child depression and CPs. However, paternal
      antisocial behavior moderated the effect of maternal depression on CPs. For
      children with antisocial fathers, CPs were observed regardless of maternal
      depression levels. In contrast, a strong relation was observed between CPs and
      maternal depression for children without antisocial fathers.

PMID- 17216346
TI  - Light exposure of the ovum and preimplantation embryo during ART procedures.
AB  - Exposure to visible light (400-700 nm wavelengths) is an unnatural stress factor
      to preimplantation embryos cultured in vitro. This study investigated the
      spectral composition and intensity of light during IVF procedures, and calculated
      radiation doses reaching the embryo during handling and manipulation. The study
      shows that normal IVF procedure may result in stressing radiation doses, unless
      filters are applied. This is at present not sufficiently recognised. No Danish
      IVF clinics use filters to protect embryos against visible light. 95% of the
      radiation was from microscopes. Ambient light, in contrast, was not a significant
      contributor to light stress and the use of dark laboratories is not justified.

PMID- 17216347
TI  - Effect of rescuing donated immature human oocytes derived after FSH/hCG
      stimulation following in vitro culture with or without Follicular Fluid Meiosis
      Activating Sterol (FF-MAS)--an embryo chromosomal and morphological analysis.
AB  - PURPOSE: Studies in mice and humans have shown that Follicular Fluid - Meiosis
      Activating Sterol (FF-MAS) induces meiotic maturation of immature oocytes in
      vitro. A multicenter, prospectively randomised study evaluated chromosomal status
      of embryos from FSH/hCG primed human immature oocytes, cultured with or without
      FF-MAS. METHODS: Denuded immature oocytes (n=365) were randomly allocated into
      inert control, FF-MAS 5 microM or 20 microM. Seventy +/-2 hours after ICSI on
      matured oocytes, all cleaved embryos were fixed for fluorescence in situ
      hybridisation analysis. RESULTS: Only 15% of oocytes resulted in cleaved embryos.
      GV oocytes matured at significantly lower rates (14% and 7%) in the two FF-MAS
      groups compared to the inert control group (47%). High rates of chromosomal
      abnormalities were found in all groups. CONCLUSION: Immature oocytes showed poor
      development with high rates of embryo chromosomal abnormalities. Exposure to FF
      MAS in the concentrations, duration and/or formulation used in this study did not
      improve the results.

PMID- 17216348
TI  - Flow perfusion improves seeding of tissue engineering scaffolds with different
      architectures.
AB  - Engineered bone grafts have been generated in static and dynamic systems by
      seeding and culturing osteoblastic cells on 3-D scaffolds. Seeding determines
      initial cellularity and cell spatial distribution throughout the scaffold, and
      affects cell-matrix interactions. Static seeding often yields low seeding
      efficiencies and poor cell distributions; thus creating a need for techniques
      that can improve these parameters. We have evaluated the effect of oscillating
      flow perfusion on seeding efficiency and spatial distribution of MC3T3-E1 pre
      osteoblastic cells in fibrous polystyrene matrices (20, 35 and 50-microm fibers)
      and foams prepared by salt leaching, using as controls statically seeded
      scaffolds. An additional control was investigated where static seeding was
      followed by unidirectional perfusion. Oscillating perfusion resulted in the most
      efficient technique by yielding higher seeding efficiencies, more homogeneous
      distribution and stronger cell-matrix interactions. Cell surface density
      increased with inoculation cell number and then reached a maximum, but
      significant detachment occurred at greater flow rates. Oxygen plasma treatment of
      the fibers greatly improved seeding efficiency. Having similar porosity and
      dimensions, fibrous matrices yielded higher cell surface densities than foams.
      Fluorescence microscopy and histological analyses in polystyrene and PLLA
      scaffolds demonstrated that perfusion seeding produced more homogeneous cell
      distribution, with fibrous matrices presenting greater uniformity than the foams.

PMID- 17216349
TI  - Determinants of allergen concentrations in apartments of asthmatic children
      living in public housing.
AB  - There is growing evidence linking poor housing conditions and respiratory
      diseases, including asthma. The association between housing conditions and asthma
      in the inner city has been attributed in part to cockroach and mouse infestation
      and the resulting allergen exposures. Multiple social and behavioral factors can
      influence environmental exposures and health conditions, necessitating a thorough
      examination of such factors. As part of the Healthy Public Housing Initiative, we
      evaluated the association between physical and household characteristics and pest
      related allergen levels in three public housing developments in Boston, MA. We
      detected cockroach allergens (Bla g 1 and Bla g 2) in bedroom air, bed, and
      especially high concentrations in kitchen samples. In multivariate Tobit
      regressions controlling for development and season, clutter and lack of
      cleanliness in the apartment were associated with a tenfold increase in Bla g 1
      concentration in the air, a sevenfold increase in Bla g 1 and an eightfold
      increase in Bla g 2 concentrations in the bed, and an 11-fold increase in Bla g 2
      in the kitchen (p<0.05 for all). Holes in the wall/ceiling were associated with a
      six- to 11-fold increase in kitchen cockroach allergen concentrations (p<0.05).
      Occupancy in an apartment unit of 2 years or more was also associated with
      increased cockroach allergen concentrations. In contrast, there were low
      concentrations of mouse urinary protein in this population. In conclusion, these
      results suggest that interventions in these homes should focus on reducing
      cockroach allergen concentrations and that building-wide interventions should be
      supplemented with targeted efforts focused on high-risk units.

PMID- 17216351
TI  - Child injury risks are close to home: parent psychosocial factors associated with
      child safety.
AB  - OBJECTIVE: In several populations, maternal depression has been associated with
      reduced child safety. In an urban pediatric Emergency Department, we examined the
      relationship between parental depression, social support, and domestic conflict
      and child safety behaviors. METHODS: We studied consecutive patients in an
      Emergency Department. Trained interviewers used a structured instrument to assess
      patient, primary caregiver, and household demographics, socio-economic status,
      psychosocial factors, child safety behaviors (whether a gun was in the home,
      poisons were locked, a functioning smoke detector was present, and use of
      carseats or seatbelts), and whether the home was smoke-free. 1,116 patients
      provided adequate data. RESULTS: Depression was associated with a modest and not
      statistically significant reduction in child safety behaviors in this population.
      Lack of social support and the presence of domestic conflict were robustly,
      independently, and statistically significantly associated with less safe homes.
      Domestic conflict was associated with more smoking in the home. CONCLUSION: In
      our population, child safety was associated less with depression and more with
      parental lack of social support and domestic conflict. These can be assessed in a
      Emergency Department and may be amenable to intervention.

PMID- 17216352
TI  - Cadmium induced oxidative stress in soybean plants also by the accumulation of
      delta-aminolevulinic acid.
AB  - Cadmium toxicity has been extensively studied in plants, however its biochemical
      mechanism of action has not yet been well established. To fulfil this objective,
      four-weeks-old soybean nodulated plants were treated with 200 muM Cd(2+) for 48
      h. delta-aminolevulinic acid dehydratase (ALA-D, E.C. 4.2.1.24) activity and
      protein expression, as well as delta-aminolevulinic acid (ALA) and
      porphobilinogen (PBG) concentrations were determined in nodules, roots and
      leaves. In vitro experiments carried out in leaves were performed using leaf
      discs to evaluate the oxidant and antioxidant properties of ALA and S-adenosyl-L:
      -methinone (SAM), respectively. Oxidative stress parameters such as
      thiobarbituric acid reactive substances (TBARS) and GSH levels as well as
      superoxide dismutase (SOD, E.C. 1.15.1.1), and guaiacol peroxidase (GPOX, E.C.
      1.11.1.7) were also determined. Cadmium treatment caused 100% inhibition of ALA-D
      activity in roots and leaves, and 72% inhibition in nodules whereas protein
      expression remained unaltered in the three studied tissues. Plants accumulated
      ALA in nodules (46%), roots (2.5-fold) and leaves (104%), respect to controls.
      From in vitro experiments using leaf discs, exposed to ALA or Cd(2+), it was
      found that TBARS levels were enhanced, while GSH content and SOD and GPOX
      activities and expressions were diminished. The protective role of SAM against
      oxidative stress generated by Cd(2+) and ALA was also demonstrated. Data
      presented in this paper let us to suggest that accumulation of ALA in nodules,
      roots and leaves of soybean plants due to treatment with Cd(2+) is highly
      responsible for oxidative stress generation in these tissues.

PMID- 17216353
TI  - Copper homeostasis gene discovery in Drosophila melanogaster.
AB  - Recent studies have shown a high level of conservation between Drosophila
      melanogaster and mammalian copper homeostasis mechanisms. These studies have also
      demonstrated the efficiency with which this species can be used to characterize
      novel genes, at both the cellular and whole organism level. As a versatile and
      inexpensive model organism, Drosophila is also particularly useful for gene
      discovery applications and thus has the potential to be extremely useful in
      identifying novel copper homeostasis genes and putative disease genes. In order
      to assess the suitability of Drosophila for this purpose, three screening
      approaches have been investigated. These include an analysis of the global
      transcriptional response to copper in both adult flies and an embryonic cell line
      using DNA microarray analysis. Two mutagenesis-based screens were also utilized.
      Several candidate copper homeostasis genes have been identified through this
      work. In addition, the results of each screen were carefully analyzed to identify
      any factors influencing efficiency and sensitivity. These are discussed here with
      the aim of maximizing the efficiency of future screens and the most suitable
      approaches are outlined. Building on this information, there is great potential
      for the further use of Drosophila for copper homeostasis gene discovery.

PMID- 17216354
TI  - Iron acquisition in Vibrio cholerae.
AB  - Vibrio cholerae, the causative agent of cholera, has an absolute requirement for
      iron and must obtain this element in the human host as well as in its varied
      environmental niches. It has multiple systems for iron acquisition, including the
      TonB-dependent transport of heme, the endogenous siderophore vibriobactin and
      several siderophores that are produced by other microorganisms. There is also a
      Feo system for the transport of ferrous iron and an ABC transporter, Fbp, which
      transports ferric iron. There appears to be at least one additional high affinity
      iron transport system that has not yet been identified. In iron replete
      conditions, iron acquisition genes are repressed by Fur. Fur also represses the
      synthesis of a small, regulatory RNA, RyhB, which negatively regulates genes for
      iron-containing proteins involved in the tricarboxylic acid cycle and respiration
      as well as genes for motility and chemotaxis. The redundancy in iron transport
      systems has made it more difficult to determine the role of individual systems in
      vivo and in vitro, but it may reflect the overall importance of iron in the
      growth and survival of V. cholerae.

PMID- 17216355
TI  - Functional specialization within the Fur family of metalloregulators.
AB  - The ferric uptake regulator (Fur) protein, as originally described in Escherichia
      coli, is an iron-sensing repressor that controls the expression of genes for
      siderophore biosynthesis and iron transport. Although Fur is commonly thought of
      as a metal-dependent repressor, Fur also activates the expression of many genes
      by either indirect or direct mechanisms. In the best studied model systems, Fur
      functions as a global regulator of iron homeostasis controlling both the
      induction of iron uptake functions (under iron limitation) and the expression of
      iron storage proteins and iron-utilizing enzymes (under iron sufficiency). We now
      appreciate that there is a tremendous diversity in metal selectivity and
      biological function within the Fur family which includes sensors of iron (Fur),
      zinc (Zur), manganese (Mur), and nickel (Nur). Despite numerous studies, the
      mechanism of metal ion sensing by Fur family proteins is still controversial.
      Other family members use metal catalyzed oxidation reactions to sense peroxide
      stress (PerR) or the availability of heme (Irr).

PMID- 17216356
TI  - Ferritins, bacterial virulence and plant defence.
AB  - The enterobacterial pathogen Erwinia chrysanthemi causes soft rot diseases on a
      wide range of plants, including the model plant Arabidopsis thaliana. This
      bacterium proliferates in the host by secreting a set of pectin degrading enzymes
      responsible for symptom development. In addition, survival of this bacterium in
      planta requires two high-affinity iron acquisition systems mediated by
      siderophores and protective systems against oxidative damages, suggesting the
      implication by both partners of accurate mechanisms controlling their iron
      homeostasis under conditions of infection. In this review, we address this
      question and we show that ferritins both from the pathogen and the host are
      subtly implicated in the control of this interplay.

PMID- 17216357
TI  - The bacterial metallome: composition and stability with specific reference to the
      anaerobic bacterium Desulfovibrio desulfuricans.
AB  - In bacteria, the intracellular metal content or metallome reflects the metabolic
      requirements of the cell. When comparing the composition of metals in
      phytoplankton and bacteria that make up the macronutrients and the trace
      elements, we have determined that the content of trace elements in both of these
      microorganisms is markedly similar. The trace metals consisting of transition
      metals plus zinc are present in a stoichometric molar formula that we have
      calculated to be as follows: Fe(1)Mn(0.3)Zn(0.26)Cu(0.03)Co(0.03)Mo(0.03). Under
      conditions of routine cultivation, trace metal homeostasis may be maintained by a
      series of transporter systems that are energized by the cell. In specific
      environments where heavy metals are present at toxic levels, some bacteria have
      developed a detoxification strategy where the metallic ion is reduced outside of
      the cell. The result of this extracellular metabolism is that the bacterial
      metallome specific for trace metals is not disrupted. One of the microorganisms
      that reduces toxic metals outside of the cell is the sulfate-reducing bacterium
      Desulfovibrio desulfuricans. While D. desulfuricans reduces metals by enzymatic
      processes involving polyhemic cytochromes c3 and hydrogenases, which are all
      present inside the cell; we report the presence of chain B cytochrome c nitrite
      reductase, NrfA, in the outer membrane fraction of D. desulfuricans ATCC 27774
      and discuss its activity as a metal reductase.

PMID- 17216358
TI  - Mate retention behavior of men and women in heterosexual and homosexual
      relationships.
AB  - Comparing the behavior of heterosexual and homosexual persons can provide insight
      into the origins of heterosexual sex differences in psychology. Evidence
      indicates that, aside from sexual partner preference, the mating psychology of
      homosexual men is sex-typical whereas that of homosexual women tends to be more
      sex-atypical. The current study examined one aspect of mating psychology, mate
      retention behavior, and tested whether homosexual men and women were sex-typical
      or sex-atypical for those mate retention tactics where heterosexual men and women
      differed. Men and women in heterosexual and homosexual relationships were asked
      to provide information regarding their partners' mate retention behavior by using
      the Mate Retention Inventory Questionnaire. Heterosexual men and women differed
      significantly for six of the 19 mate retention tactics considered. With respect
      to the six mate retention tactics where heterosexual sex differences existed,
      homosexual men behaved in a sex-typical manner for five of the tactics, whereas
      homosexual women behaved in a sex-atypical manner for all six tactics. We discuss
      the significance of these findings for explaining the origins of the mate
      retention behavior of heterosexual men and women. In addition, we consider what
      the pattern of sex-typical and sex-atypical mating psychology among homosexual
      men and women, respectively, suggests in regard to sex differences in the
      development of mating psychology and the development of homosexual persons.

PMID- 17216359
TI  - Allelochemical induction of cytochrome P450 monooxygenases and amelioration of
      xenobiotic toxicity in Helicoverpa zea.
AB  - Polyphagous herbivores encounter allelochemicals as complex mixtures in their
      host plants, and the toxicity of an individual compound may be influenced by the
      chemical matrix in which it is encountered. Certain plant constituents may reduce
      toxicity of cooccurring compounds by inducing detoxification systems, including
      cytochrome P450s, which can metabolize a broad range of substances. The
      polyphagous corn earworm Helicoverpa zea encounters a diversity of plant
      allelochemicals in its many host plants and, as well, can encounter aflatoxins,
      mycotoxins produced by Aspergillus flavus and Aspergillus parasiticus that infect
      damaged grains. Dietary supplementation of each of three plant allelochemicals
      that are frequently (coumarin, COU), occasionally (indole-3-carbinol, 13C), or
      rarely (xanthotoxin, XAN) encountered by H. zea larvae substantially reduced the
      toxicity of aflatoxin B1 (AFB1) to H. zea. Compared to fourth instars on diets
      containing 1 microg/g AFB1 that failed to develop and pupate, fourth instars on
      diets containing I3C and XAN increased in mass by 216.1 and 700% after 6 days,
      and pupated at rates of 40 and 88%, respectively. Diets containing COU or XAN
      also significantly reduced the mortality rates of caterpillars exposed to the
      insecticides, diazinon and carbaryl. Diets containing COU and XAN increased
      CYP6B8 transcripts 2.6-fold; CYP321A1 transcripts increased 20.7, 8.3, and 10.6
      fold in response to COU, I3C, and XAN, respectively. These results indicate that
      consumption of plant allelochemicals can ameliorate toxicity of natural and
      synthetic toxins encountered by insects, and they suggest that P450s induced by
      these allelochemicals contribute to detoxification of these chemicals in H. zea.

PMID- 17216361
TI  - Electrophysiological and behavioral responses of Ips subelongatus to
      semiochemicals from its hosts, non-hosts, and conspecifics in China.
AB  - Volatiles from hosts, non-hosts, interspecifics, and conspecifics of the Asian
      larch bark beetle, Ips subelongatus Motsch., were analyzed using both gas
      chromatographic-electroantennographic detection (GC-EAD) and gas
      chromatography/mass spectrometry (GC-MS) techniques, and field trapping bioassays
      in Inner Mongolia, China. GC-EAD experiments indicated that I. subelongatus
      antennae (both sexes) strongly responded not only to the major male-produced
      conspecific components, ipsenol, and ipsdienol, but also to other bark beetle
      compounds (cis-verbenol and verbenone), host monoterpenes (alpha-pinene, beta
      pinene, and para-cymene) from Larix sp. logs, and non-host leaf (green leaf
      volatiles and geranyl acetone) and bark (C8-alcohols and trans-conophthorin)
      volatiles. Repeatable EAD responses were also found to two compounds from hindgut
      extracts that are undetectable by GC. One of these minor compounds was identified
      as amitinol. Field trapping experiments showed that the EAD-active, major male
      hindgut component, racemic ipsenol, is the only individual compound that
      significantly attracted both sexes of I. subelongatus, whereas all other
      compounds, including previously reported pheromone components of European Ips
      cembrae, ipsdienol and 3-methyl-3-buten-1-ol, were unattractive. Ipsdienol, 3
      methyl-3-buten-1-ol, or their binary blend had no synergistic or antagonistic
      effects on I. subelongatus attraction when combined with ipsenol, whereas cis
      verbenol (a synomone) and verbenone (the antiaggregation semiochemical) inhibited
      its attraction to the ipsenol-containing attractive blend. A mixture of three EAD
      active host monoterpenes, alpha-pinene, beta-pinene, and para-cymene, was
      unattractive, but interrupted the pheromone response of I. subelongatus. Geranyl
      acetone, one of the strong EAD-active non-host volatiles also significantly
      reduced the number of I. subelongatus captured in traps baited with ipsenol
      containing attractive blend. Our results add support to the recent phylogenetic
      finding that European and Asian larch bark beetles should be regarded as two
      distinct species: I. cembrae infecting larch in Europe and I. subelongatus
      infesting larch in Asia.

PMID- 17216360
TI  - Do elevated temperature and CO2 generally have counteracting effects on phenolic
      phytochemistry of boreal trees?
AB  - Global climate change includes concomitant changes in many components of the
      abiotic flux necessary for plant life. In this paper, we investigate the combined
      effects of elevated CO2 (720 ppm) and temperature (+2 K) on the phytochemistry of
      three deciduous tree species. The analysis revealed that elevated CO(2) generally
      stimulated increased carbon partitioning to various classes of phenolic
      compounds, whereas an increase in temperature had the opposite effect. The
      combined effects of both elevated CO2 and temperature were additive, i.e.,
      canceling one another's individual effects. Obviously, the effects of global
      climate change on leaf chemistry must simultaneously consider both temperature
      and CO2. If these results are generally applicable, then the counteracting effect
      of the temperature is likely to play a major role in alpine, boreal, and arctic
      zones in determining the balance between populations of plants and herbivores.

PMID- 17216362
TI  - Induction of oxidative stress by sunflower phytotoxins in germinating mustard
      seeds.
AB  - The aim of this study was to investigate the phytotoxic effect of sunflower on
      physiological and biochemical processes during germination of mustard seeds
      (Sinapis alba L. cv. Nakielska). To exclude the involvement of osmotic stress in
      seed reaction to phytotoxic compounds, we compared the effect of 10% (w/v) water
      extract from sunflower (Helianthus annuus L. cv. Ogrodowy) leaves and 28.4% (w/v)
      polyethylene glycol (PEG) 8000 solution characterized by an equal Psi = -1 MPa.
      We evaluated (1) the amount of hydrogen peroxide (H2O2); (2) activities of
      antioxidant enzymes: superoxide dismutase, catalase, and glutathione reductase;
      (3) membrane permeability; and (4) level of malondialdehyde (MDA). Both,
      sunflower compounds and PEG solutions inhibited mustard seed germination, but
      only phytotoxins caused an increase in the cell membrane permeability, MDA level,
      H2O2 concentration, and alterations in activities of antioxidant enzymes. Our
      results demonstrate that despite the activation of the antioxidant system by
      sunflower phytotoxins, reactive oxygen species accumulation caused cellular
      damage, which resulted in the decrease of germinability and gradual loss of seed
      vigor. It seems that the negative effect of sunflower on germination of mustard
      seeds is mostly because of its toxicity and not to its contribution to osmotic
      potential.

PMID- 17216363
TI  - Modeling the tertiary structure of the patatin domain of neuropathy target
      esterase.
AB  - Neuropathy target esterase (NTE) is a transmembrane protein of unknown function
      whose specific chemical modification by certain organophosphorus (OP) compounds
      leads to distal axonopathy. Therefore, solving the 3D structure of NTE would
      advance the understanding of its pathogenic and physiologic roles. In this study,
      the tertiary structures of the patatin (catalytic) domain and the N-terminal
      transmembrane domain of NTE were modeled using the crystal structures of patatin
      (PDB ID 1oxw) and moricin (PDB ID 1kv4) as templates. Sequence alignments and
      secondary structure predictions were obtained from the INUB server (Buffalo, NY).
      O and PyMol were used to build the PNTE and NTE TMD chains from these sequence
      alignments. The PNTE model was refined in the presence of water using the
      crystallography and NMR system, while the NTE TMD model was refined in vacuo
      using the GROMOS implementation in the Swiss PDB viewer. The modeled active site
      of NTE was found to consist of a Ser966-Asp1086 catalytic dyad, which is
      characteristic of phospholipase A2 enzymes. The Ser966 Ogamma was located 2.93 A
      from the Odelta2 of Asp1086. In addition, our NTE model was found to contain a
      single N-terminal transmembrane domain. This modeling effort provided structural
      and mechanistic predictions about the catalytic domain of NTE that are being
      verified via experimental techniques.

PMID- 17216364
TI  - Comparative membrane channel size and activity of botulinum neurotoxins A and E.
AB  - In an effort to compare the molecular basis of differential toxic activity of
      botulinum neurotoxin A (BoNT/A) and BoNT/E, we have analyzed their membrane
      channel activity by measuring calcein release from liposomes. Both BoNT/A and /E
      showed a same level of membrane channel activity that was specifically blocked by
      IgG specific to the neurotoxins. With the use of fluorescein-labeled dextran, we
      determined that the size of the channel is at least 24.2 A which is appropriate
      for the translocation of a protein of 50 kDa (the light chain of BoNT). These
      findings would suggest that the difference in the toxicity level of the two BoNT
      serotypes might reflect differences in either endopeptidase activity or their
      binding to receptor(s).

PMID- 17216365
TI  - A self-paced brain interface system that uses movement related potentials and
      changes in the power of brain rhythms.
AB  - Movement execution results in the simultaneous generation of movement-related
      potentials (MRP) as well as changes in the power of Mu and Beta rhythms. This
      paper proposes a new self-paced multi-channel BI that combines features extracted
      from MRPs and from changes in the power of Mu and Beta rhythms. We developed a
      new algorithm to classify the high-dimensional feature space. It uses a two-stage
      multiple-classifier system (MCS). First, an MCS classifies each neurological
      phenomenon separately using the information extracted from specific EEG channels
      (EEG channels are selected by a genetic algorithm). In the second stage, another
      MCS combines the outputs of MCSs developed in the first stage. Analysis of the
      data of four able-bodied subjects shows the superior performance of the proposed
      algorithm compared with a scheme where the features were all combined in a single
      feature vector and then classified.

PMID- 17216366
TI  - Losing a giant's shoulders to stand on: will we still be able to see the forest
      for the trees?

PMID- 17216367
TI  - Reflections on George Albee's legacy of promoting human potential and social
      justice.

PMID- 17216368
TI  - Evaluation of uncertainty parameters estimated by different population PK
      software and methods.
AB  - The uncertainty associated with parameter estimations is essential for population
      model building, evaluation, and simulation. Summarized by the standard error
      (SE), its estimation is sometimes questionable. Herein, we evaluate SEs provided
      by different non linear mixed-effect estimation methods associated with their
      estimation performances. Methods based on maximum likelihood (FO and FOCE in
      NONMEM, nlme in Splus, and SAEM in MONOLIX) and Bayesian theory (WinBUGS) were
      evaluated on datasets obtained by simulations of a one-compartment PK model using
      9 different designs. Bootstrap techniques were applied to FO, FOCE, and nlme. We
      compared SE estimations, parameter estimations, convergence, and computation
      time. Regarding SE estimations, methods provided concordant results for fixed
      effects. On random effects, SAEM and WinBUGS, tended respectively to under or
      over-estimate them. With sparse data, FO provided biased estimations of SE and
      discordant results between bootstrapped and original datasets. Regarding
      parameter estimations, FO showed a systematic bias on fixed and random effects.
      WinBUGS provided biased estimations, but only with sparse data. SAEM and WinBUGS
      converged systematically while FOCE failed in half of the cases. Applying
      bootstrap with FOCE yielded CPU times too large for routine application and
      bootstrap with nlme resulted in frequent crashes. In conclusion, FO provided bias
      on parameter estimations and on SE estimations of random effects. Methods like
      FOCE provided unbiased results but convergence was the biggest issue. Bootstrap
      did not improve SEs for FOCE methods, except when confidence interval of random
      effects is needed. WinBUGS gave consistent results but required long computation
      times. SAEM was in-between, showing few under-estimated SE but unbiased parameter
      estimations.

PMID- 17216369
TI  - Damage index assessment and quality of life in systemic lupus erythematosus
      patients (with long-term disease) in Northeastern Brazil.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease that affects mainly
      young women. During the disease course, many organs and systems can suffer non
      reversible damage that decreases both the patient's life span and also their
      quality of life. To determine the chronic damage and its correlation with quality
      of life, the Systemic Lupus International Collaborating Clinics/American College
      of Rheumatology Damage Index was used in 63 patients who met the ACR criteria for
      SLE. Quality of life (QOL) was measured through the Medical Outcomes Survey short
      form 36 (SF-36), sociodemographic data were assessed using specific
      questionnaires, and disease activity was measured by the systemic lupus
      erythematosus disease activity index. Overall, 32% of the patients presented
      damage. Neuropsychiatric (25%) and vascular (20%) involvement were the most
      frequently related. Organic damages were associated with disease duration (p <
      0.03). General health status and social aspects of quality of life were also
      associated with disease duration (p < 0.05 and p < 0.038, respectively).
      Socioeconomic status and disease activity were not associated with organic
      damages and quality of life. This study concluded that disease activity,
      cumulative damage, and quality of life had some influence in the overall view of
      lupus but those parameters are distinct domains of health status in SLE. Our
      analysis identified that disease duration had an important association with
      damage index and general health status.

PMID- 17216370
TI  - Evaluation of pulmonary function and bicycle ergometry tests in patients with
      Behcet's disease.
AB  - Behcet's disease (BD) has well-defined pulmonary complications, but
      cardiopulmonary exercise testing and the strength of the respiratory muscles have
      not been studied in detail. We aimed to investigate the pulmonary functions
      tests, inspiratory and expiratory muscle strength and endurance, cardiopulmonary
      exercise test response, and the relationship of these parameters in patients with
      BD. Forty BD patients and 20 healthy control subjects were recruited for this
      study. Mean age was 32.95 +/- 7.66 years for the BD group and 33.85 +/- 6.63
      years for the control group with no statistically significant difference. The
      ratios of slight obstructive ventilatory impairment were 32.5% for the BD group.
      When the values of pulmonary function tests were compared, no statistically
      significant difference was found in FEV(1)/FVC (Forced expiratory volume during
      the first second/forced vital capacity), or maximal midexpiratory flow rate (all
      in percent) values between patient and control groups. Maximal inspiratory and
      expiratory pressures, peak expiratory flow rate (in percent) and maximal
      voluntary ventilation (in percent) values were significantly lower than those of
      the control group. Body's consumption of peak oxygen (VO(2peak)), oxygen
      consumption (milliliters per kilogram per minute), anaerobic threshold (AT),
      maximum exercise ventilation (VE(max)), work load values, and exercise test time
      in the bicycle exercise test were significantly higher in control groups than in
      patients with BD. The values of heart rate reserve, breathing reserve, and
      VE/VCO(2) at the AT of BD patients were within normal limits We conclude that
      respiratory and aerobic exercise may be recommended to improve respiratory muscle
      strength and endurance as well as the aerobic capacity and maximal ventilatory
      capacity in patients with BD.

PMID- 17216371
TI  - Neonaticides may be more preventable and heterogeneous than previously thought -
      neonaticides in Finland 1980-2000.
AB  - Neonaticide is a sad and infrequent crime with possibly a high level of
      underreporting. The aim of this study was to examine the circumstances of
      neonaticide, and whether there are subtypes of offenders, or suggestions for
      prevention. The study was retrospective and register-based using comprehensive
      nation-wide material of all cases of suspected neonaticide during 1980-2000 in
      Finland. Out of the 50 suspected cases, 32 women were included in the final
      analyses as neonaticide offenders. Most women (91%) had concealed their
      pregnancy, which was not the first for 66%. Most (66%) were not quite sure why
      they had offended, and the most frequent (63%) method of operation was neglect.
      Four women were diagnosed psychotic and formed a specific group. We concluded
      that there might be specific subgroups of offenders - even though our small
      population limited conclusions. Furthermore, prevention might be heightened. We
      call for international joint projects for enlarged material to enable grouping,
      as well as education and discussion among the public and the professionals to
      prevent neonaticide, unify its jurisprudence and improve the treatment of the
      offenders.

PMID- 17216373
TI  - Fusiform aneurysm of the superior cerebellar artery: short review article.
AB  - Fusiform superior cerebellar artery (SCA) aneurysms are quite rare and only 9
      cases have been reported in the literature. Fusiform aneurysms are a small group
      of cerebral aneurysms among the most difficult to treat. The therapeutic
      approaches in the limited number cited in the literature include surgery and
      endovascular occlusion. Surgical techniques which have been used are parent
      artery occlusion, trapping or body clipping of the bleeding site, and wrapping
      for fusiform aneurysms. Neurological condition, presence of collateral
      circulation, type and configuration of the aneurysm, and type of the dissection
      are important factors that predict the course of fusiform SCA aneurysms. We
      reviewed the literature on fusiform aneurysm of the SCA and report a further case
      treated surgically.

PMID- 17216372
TI  - Continuous cerebral PtO2 measurements in awake patients as a diagnostic tool in
      suspected chronic adult hydrocephalus--a retrospective study of 10 cases.
AB  - BACKGROUND: During the last decade of the 20th century, continuous invasive
      PtO(2) recording has become a widely accepted and well-established means of
      monitoring patients with acute traumatic or spontaneous cerebral lesions. It is
      considered a safe and reliable tool for the detection of hypoxia in the ICU
      setting. However, while invasive measurements of intracranial pressure are being
      used both in the ICU and in standard diagnostic protocols for suspected chronic
      adult hydrocephalus the same has not yet happened in relation to PtO(2)
      recordings. METHODS: We report our experience with the first 10 patients who have
      been evaluated for suspected CAH applying a protocol that includes continuous
      cerebral PtO(2) measurements. The relationship between PtO(2) and ICP including a
      characteristic wave pattern (inverse waves) on the PtO(2) curve is analyzed and
      clinical and outcome data are recorded. RESULTS AND CONCLUSIONS: 1. PtO(2)
      recording in awake patients is safe and reliable. 2. The combination of classical
      Lundberg waves in the ICP recording with phases of inverse waves in the PtO(2)
      recording may predict good outcome after shunting. 3. The effect of concomitant
      conditions on the brain oxygenation can be estimated for individual patients and
      used as a negative predictor for surgical outcome. 4. Invasive intracranial
      monitoring is not free of potentially serious bleeding complications and can only
      be performed with risk enhancing factors (AVM/haemorrhagic diathesis) excluded.

PMID- 17216374
TI  - Influence of flat-panel fluoroscopic equipment variables on cardiac radiation
      doses.
AB  - PURPOSE: To assess the influence of physician-selectable equipment variables on
      the potential radiation dose reductions during cardiac catheterization
      examinations using modern imaging equipment. MATERIALS: A modern bi-plane
      angiography unit with flat-panel image receptors was used. Patients were
      simulated with 15-30 cm of acrylic plastic. The variables studied were: patient
      thickness, fluoroscopy pulse rates, record mode frame rates, image receptor field
      of-view (FoV), automatic dose control (ADC) mode, SID/SSD geometry setting,
      automatic collimation, automatic positioning, and others. RESULTS: Patient
      radiation doses double for every additional 3.5-4.5 cm of soft tissue. The dose
      is directly related to the imaging frame rate; a decrease from 30 pps to 15 pps
      reduces the dose by about 50%. The dose is related to [(FoV)(-N )] where 2.0 < N
      < 3.0. Suboptimal positioning of the patient can nearly double the dose. The ADC
      system provides three selections that can vary the radiation level by 50%. For
      pediatric studies (2-5 years old), the selection of equipment variables can
      result in entrance radiation doses that range between 6 and 60 cGy for diagnostic
      cases and between 15 and 140 cGy for interventional cases. For adult studies, the
      equipment variables can produce entrance radiation doses that range between 13
      and 130 cGy for diagnostic cases and between 30 and 400 cGy for interventional
      cases. CONCLUSIONS: Overall dose reductions of 70-90% can be achieved with
      pediatric patients and about 90% with adult patients solely through optimal
      selection of equipment variables.

PMID- 17216376
TI  - A 16-gauge sheath needle used as an introducer system for PTA of arteriovenous
      fistulas minimizing venous injury.

PMID- 17216375
TI  - Magnetic resonance imaging of acute reperfused myocardial infarction:
      intraindividual comparison of ECIII-60 and Gd-DTPA in a swine model.
AB  - PURPOSE: To compare a necrosis-avid contrast agent (NACA) bis-Gd-DTPA-pamoic acid
      derivative (ECIII-60) after intracoronary delivery with an extracellular agent Gd
      DTPA after intravenous injection on magnetic resonance imaging (MRI) in a swine
      model of acute reperfused myocardial infarction (MI). METHODS: Eight pigs
      underwent 90 min of transcatheter coronary balloon occlusion and 60 min of
      reperfusion. After intravenous injection of Gd-DTPA at a dose of 0.2 mmol/kg, all
      pigs were scanned with T1-weighted MRI until the delayed enhancement of MI
      disappeared. Then they were intracoronarily infused with ECIII-60 at 0.0025
      mmol/kg and imaged for 5 hr. Signal intensity, infarct-over-normal contrast ratio
      and relative infarct size were quantified, compared, and correlated with the
      results of postmortem MRI and triphenyltetrazolium chloride (TTC) histochemical
      staining. RESULTS: A contrast ratio over 3.0 was induced by both Gd-DTPA and
      ECIII-60. However, while the delayed enhancement with Gd-DTPA virtually vanished
      in 1 hr, ECIII-60 at an 80x smaller dose depicted the MI accurately over 5 hr as
      proven by ex vivo MRI and TTC staining. CONCLUSION: Both Gd-DTPA and ECIII-60
      strongly enhanced acute MI. Comparing with fading contrast in a narrow time
      window with intravenous Gd-DTPA, intracoronary ECIII-60 persistently demarcated
      the acute MI, indicating a potential method for postprocedural assessment of
      myocardial viability after coronary interventions.

PMID- 17216377
TI  - Complications in percutaneous vertebroplasty associated with puncture or cement
      leakage.
AB  - Due to the minimally invasive character and excellent clinical outcome of
      percutaneous vertebroplasty (PVP), the procedure is being performed in greatly
      increasing numbers. While PVP has a low complication rate in general, severe
      complications can occur. We focus on the imaging appearance of complications of
      PVP associated with puncture or cement leakage--from harmless to life
      threatening.

PMID- 17216378
TI  - Treatment of a persistent false lumen with aneurysm formation following surgical
      repair of type a dissection.
AB  - We describe the case of a 68-year-old man who developed aneurysmal dilatation of
      the proximal descending thoracic aorta 8 years after repair of a type A
      dissection. The aneurysm was due to an anastomotic leak at the distal end of the
      previous repair in the ascending aorta with antegrade perfusion of the false
      lumen. Surgical repair of the anastomotic leak partially obliterated the false
      lumen and computed tomography scan demonstrated thrombosis in a large proportion
      of the false lumen aneurysm. Follow-up with surveillance scans showed persistent
      filling of this aneurysm due to retrograde flow of blood within the false lumen.
      Coil embolization of the false lumen within the thoracic aorta was performed
      which successfully thrombosed the aneurysm with a reduction in diameter. Late
      aneurysm formation may complicate type A dissection repairs during follow-up due
      to a persistent false lumen, especially if there is an anastomotic leak. This
      case report describes a strategy to deal with this difficult clinical problem.

PMID- 17216379
TI  - Reflex anuria after renal tumor embolization.
AB  - We report a case of reflex anuria after transarterial embolization of a renal
      tumor. Anuria developed immediately after embolization and resolved 74 hr
      following the procedure. We postulate that reflux anuria in our case was related
      to mechanoreceptors, chemoreceptors, or both, as these are stimulated by the
      occluded blood vessels, ischemia, and edema of the normal renal tissue of an
      embolized kidney.

PMID- 17216380
TI  - Experimental evaluation of early and long-term effects of microparticle
      embolization in two different mini-pig models. Part I: kidney.
AB  - PURPOSE: Using a pig model: (1) to evaluate the vascular distribution pattern,
      including the homogeneity and completeness of the intra-arterial microsphere
      distribution, of 40-120-microm trisacryl-gelatin microspheres (Embospheres) in
      acute whole-kidney embolization; (2) to evaluate the durability and
      biocompatibility of 40-120-microm trisacryl-gelatin microspheres (Embospheres) in
      chronic partial kidney embolization. METHODS: Twenty-two animals were divided
      into four groups: group 1 (n = 4) underwent total arterial renal occlusion with
      immediate euthanasia. Groups 2-4 had chronic superselective and partial renal
      embolization with increasing follow-up times: group 2 (n = 2), 1 week; group 3 (n
      = 7), 4 weeks; and group 4 (n = 9), 14 weeks. Key endpoints in group 1 were
      homogeneity and completeness of acute embolizations. In groups 2-4 the key
      endpoints were durability of embolization and particle-related inflammation in
      chronic partial embolizations as assessed by quantitative angiography or
      histomorphometry. A numerical angiographic occlusion score (0.0 to 4.0, where 3.0
      is optimal) was developed to assess and quantify the angiographic durability of
      superselective embolizations (groups 2-4). RESULTS: In group 1, a relatively
      homogeneous distribution of the particles from segmental arteries to the
      precapillary level was shown by histomorphometry. Some particles reached the
      glomerular vas afferens (10 microm diameter). In groups 2-4, a mild
      recanalization appeared during follow-up. The immediate average postembolization
      occlusion score of 3.18 +/- 0.73 was reduced to 1.44 +/- 0.73 (statistically
      significant). Microscopy revealed subtotal necrosis but no foreign body granuloma
      formation. The intra-arterial appearance of giant cells closely attaching to the
      surface of the embolic spheres inside the vessel lumen was noted. Vessel walls
      showed major ischemic reactions. CONCLUSION: Microspheres 40-120 microm in
      diameter might achieve total occlusion of the arterial kidney vasculature when
      injected centrally as a result of their fairly homogeneous distribution.
      Segmental renal infarction occurs after chronic partial embolization despite
      recanalizations during follow-up. Only mild specific intra-arterial foreign body
      reactions were found.

PMID- 17216381
TI  - Efficacy of intra-arterial infusion chemotherapy for head and neck cancers using
      coaxial catheter technique: initial experience.
AB  - The aim of this study was to evaluate the efficacy of intra-arterial infusion
      chemotherapy for head and neck cancers using a coaxial catheter technique: the
      superficial temporal artery (STA)-coaxial catheter method. Thirty-one patients
      (21 males and 10 females; 37-83 years of age) with squamous cell carcinoma of the
      head and neck (maxilla, 2; epipharynx, 4; mesopharynx, 8; oral floor, 4; tongue,
      10; lower gingiva, 1; buccal mucosa, 2) were treated by intra-arterial infusion
      chemotherapy. Four patients were excluded from the tumor-response evaluation
      because of a previous operation or impossibility of treatment due to catheter
      trouble. Forty-eight sessions of catheterization were performed. A guiding
      catheter was inserted into the STA and a microcatheter was advanced into the
      tumor-feeding artery via the guiding catheter under angiographic guidance. When
      the location of the tumor or its feeding artery was uncertain on angiography,
      computed tomographic angiography was performed. The anticancer agent carboplatin
      (CBDCA) was continuously injected for 24 h through the microcatheter from a
      portable infusion pump attached to the patient's waist. The total administration
      dose was 300-1300 mg per body. External radiotherapy was administered during
      intra-arterial chemotherapy at a total dose of 21-70.5 Gy. The initial response
      was complete response in 15 patients, partial response in 7 patients, and no
      change in 5 patients; the overall response rate was 81.5% (22/27). Complication
      related catheter maintenance was observed in 15 of 48 sessions of
      catheterization. Injury and dislocation of the microcatheter occurred 10 times in
      7 patients. Catheter infection was observed three times in each of two patients,
      and catheter occlusion and vasculitis occurred in two patients. Intra-arterial
      infusion chemotherapy via the STA-coaxial catheter method could have potential as
      a favorable treatment for head and neck tumors.

PMID- 17216383
TI  - Concurrent sound segregation in electric and acoustic hearing.
AB  - We investigated potential cues to sound segregation by cochlear implant (CI) and
      normal-hearing (NH) listeners. In each presentation interval of experiment 1a, CI
      listeners heard a mixture of four pulse trains applied concurrently to separate
      electrodes, preceded by a "probe" applied to a single electrode. In one of these
      two intervals, which the subject had to identify, the probe electrode was the
      same as a "target" electrode in the mixture. The pulse train on the target
      electrode had a higher level than the others in the mixture. Additionally, it
      could be presented either with a 200-ms onset delay, at a lower rate, or with an
      asynchrony produced by delaying each pulse by about 5 ms re those on the
      nontarget electrodes. Neither the rate difference nor the asynchrony aided
      performance over and above the level difference alone, but the onset delay
      produced a modest improvement. Experiment 1b showed that two subjects could
      perform the task using the onset delay alone, with no level difference.
      Experiment 2 used a method similar to that of experiment 1, but investigated the
      onset cue using NH listeners. In one condition, the mixture consisted of
      harmonics 5 to 40 of a 100-Hz fundamental, with the onset of either harmonics 13
      to 17 or 26 to 30 delayed re the rest. Performance was modest in this condition,
      but could be improved markedly by using stimuli containing a spectral gap between
      the target and nontarget harmonics. The results suggest that (a) CI users are
      unlikely to use temporal pitch differences between adjacent channels to separate
      concurrent sounds, and that (b) they can use onset differences between channels,
      but the usefulness of this cue will be compromised by the spread of excitation
      along the nerve-fiber array. This deleterious effect of spread-of-excitation can
      also impair the use of onset cues by NH listeners.

PMID- 17216384
TI  - Development and characterization of two new cell lines from milkfish (Chanos
      chanos) and grouper (Epinephelus coioides) for virus isolation.
AB  - Two new cell lines, SIMH and SIGE, were derived from the heart of milkfish
      (Chanos chanos), a euryhaline teleost, and from the eye of grouper (Epinephelus
      coioides), respectively. These cell lines were maintained in Leibovitz's L-15
      supplemented with 20% fetal bovine serum (FBS). The SIMH cell line was
      subcultured more than 50 times over a period of 210 days and SIGE cell line has
      been subcultured 100 times over a period of 1 1/2 years. The SIMH cell line
      consists predominantly of fibroblastic-like cells. The SIGE cell line consists
      predominantly of epithelial cells. Both the cell lines were able to grow at
      temperatures between 25 and 32 degrees C with an optimum temperature of 28
      degrees C. The growth rate of these cells increased as the proportion of FBS
      increased from 2% to 20% at 28 degrees C with optimum growth at the
      concentrations of 15% or 20% FBS. Seven marine fish viruses were tested to
      determine the susceptibility of these cell lines. The SIGE cell line was found to
      be susceptible to nodavirus, MABV NC-1 and Y6, and the infection was confirmed by
      cytopathic effect (CPE) and reverse transcriptase-polymerase chain reaction. When
      these cells were transfected with pEGFP-N1 vector DNA, significant fluorescent
      signals were observed, suggesting that these cell lines can be a useful tool for
      transgenic and genetic manipulation studies. Further, these cell lines are
      characterized by immunocytochemistry using confocal laser scanning microscopy
      (CFLSM).

PMID- 17216386
TI  - Dysphagia management: an analysis of patient outcomes using VitalStim therapy
      compared to traditional swallow therapy.
AB  - This study compares the outcomes using VitalStim therapy to outcomes using
      traditional swallowing therapy for deglutition disorders. Twenty-two patients had
      an initial and a followup videofluoroscopic swallowing study or fiberoptic
      endoscopic evaluation of swallowing and were divided into an experimental group
      that received VitalStim treatments and a control group that received traditional
      swallowing therapy. Outcomes were analyzed for changes in oral and pharyngeal
      phase dysphagia severity, dietary consistency restrictions, and progression from
      nonoral to oral intake. Results of chi(2) analysis showed no statistically
      significant difference in outcomes between the experimental and control groups.

PMID- 17216385
TI  - Part 1. Automated change detection and characterization in serial MR studies of
      brain-tumor patients.
AB  - The goal of this study was to create an algorithm which would quantitatively
      compare serial magnetic resonance imaging studies of brain-tumor patients. A
      novel algorithm and a standard classify-subtract algorithm were constructed. The
      ability of both algorithms to detect and characterize changes was compared using
      a series of digital phantoms. The novel algorithm achieved a mean sensitivity of
      0.87 (compared with 0.59 for classify-subtract) and a mean specificity of 0.98
      (compared with 0.92 for classify-subtract) with regard to identification of
      voxels as changing or unchanging and classification of voxels into types of
      change. The novel algorithm achieved perfect specificity in seven of the nine
      experiments. The novel algorithm was additionally applied to a short series of
      clinical cases, where it was shown to identify visually subtle changes. Automated
      change detection and characterization could facilitate objective review and
      understanding of serial magnetic resonance imaging studies in brain-tumor
      patients.

PMID- 17216387
TI  - Dynamics of capsule swallowing by healthy young men and capsule transit time from
      the mouth to the stomach.
AB  - We examined the dynamics of capsule swallowing by healthy young men using the
      anterior-posterior view of videofluoroscopy as a first step in a study on capsule
      swallowing by dysphagic patients. The subjects were 14 healthy men who did not
      have any complaint of dysphagia. They were asked to swallow a #4 hard gelatin
      capsule filled with barium sulfate with 15 ml of water during the
      videofluoroscopic examination. This examination was repeated three times for each
      subject (total of 42 trials). In four of the 14 subjects, a swallowed capsule was
      retained at the upper esophageal sphincter, or the broncho-aortic constriction of
      the esophagus, or the lower esophageal sphincter. Except where retention
      occurred, the average capsule transit time from the mouth to the stomach was 6.0
      +/- 2.4 s. Three of the four subjects who had capsule retention did not realize
      that the swallowed capsule was retained en route to the stomach. By considering
      the dynamics of swallowing a capsule with 15 ml of water in healthy men, we
      should be able to reveal the dynamics of capsule swallowing in dysphagic
      patients, and the capsule transit time from the mouth to the stomach.

PMID- 17216388
TI  - Laryngeal penetration during deglutition in normal subjects of various ages.
AB  - This study examined the frequency of penetration of liquid, paste, and masticated
      materials into the airway during videofluoroscopic studies of normal swallow in
      98 normal subjects who were from 20 to 94 years of age. The purposes of the study
      were to define frequency and level of penetration using the penetration
      aspiration scale as a result of age, bolus volume, viscosity, and gender, and to
      describe the body's sensorimotor response to the penetration based on audible
      coughs or throat clearing on the audio channel of each videotaped fluoroscopic
      study. Frequencies of penetration were defined in relation to bolus volume, age,
      gender, and bolus viscosity from swallows of 1, 3, 5, and 10 ml and cup-drinking
      of thin liquids; 3 ml of pudding; (1/4) of a Lorna Doone cookie; and a bite of an
      apple. Results showed that penetrations were significantly more frequent after
      age 50 and thick viscosities penetrated only in subjects age 50 and over. For
      persons under 50, 7.4% of swallows exhibited penetration, while for people age 50
      and over, 16.8% of swallows showed penetration. Significantly more penetration
      occurred on larger liquid boluses. There was no relationship between gender and
      frequency of penetration. None of the subjects that penetrated showed a
      sensorimotor response to the penetration, which may relate to the relatively
      shallow depth of the penetration.

PMID- 17216389
TI  - Time-dependent rheology of starch thickeners and the clinical implications for
      dysphagia therapy.
AB  - The viscosity of nonsolid foods and the stability of their viscosity over time is
      critical in managing dysphagia. The time-dependent viscosity of liquids thickened
      with starch-based thickeners was measured at constant temperature and shear rate.
      Viscosity was measured between 30-min intervals of rest (zero shear) over a
      period of 17 h at 20.0 degrees C. Two common types of thickeners were evaluated:
      maize-based and maltodextrin-based (the latter commonly used in pediatrics). The
      maize-based thickeners undergo a significant decrease in viscosity over the
      initial 1-4 h following preparation. The maltodextrin-based thickener's viscosity
      increases significantly 30 min following preparation and is then more stable over
      time than its maize-based equivalent. These findings suggest that the success of
      current dysphagia therapies that use thickeners could be influenced by the time
      dependent nature of thickened fluid viscosity. Acknowledgment and appropriate
      selection of the thickener type is shown to be of great importance.

PMID- 17216390
TI  - Anterior cervical osteophytes causing dysphagia and dyspnea: an uncommon entity
      revisited.
AB  - Large anterior cervical osteophytes can occur in degeneration of the cervical
      spine or in diffuse idiopathic skeletal hyperostosis (DISH). We present the case
      of an 83-year-old patient with progressive dysphagia and acute dyspnea,
      necessitating emergency tracheotomy. Voluminous anterior cervical osteophytes
      extending from C3 to C7 and narrowing the pharyngoesophageal segment by external
      compression and bilateral vocal fold immobility were diagnosed radiologically and
      by fiberoptic laryngoscopy. Surgical removal of all osteophytes led to the
      resolution of symptoms. Dyspnea with or without dysphagia caused by hypertrophic
      anterior cervical osteophytes is an uncommon entity. The exhaustive diagnostic
      workup proposed in the literature could be simplified by using fiberoptic
      laryngoscopy and dynamic videofluoroscopy. The causes, treatment, and outcome are
      discussed.

PMID- 17216391
TI  - Surgery for aspiration: analysis of laryngotracheal separation in 23 children.
AB  - The aim of this study was to analyze the efficacy of laryngotracheal separation
      (LTS) in eliminating aspiration in children by comparing pre- and postoperative
      conditions. This prospective study used an internal control group. Children with
      neurologic impairment and a diagnosis of chronic aspiration were subjected to LTS
      at the Associacao de Assistencia a Crianca Deficiente (AACD). Twenty-three
      children had undergone LTS with the modified Lindeman technique. All of them
      gained complete control of aspiration. Frequency of hospitalization, number of
      respiratory infections, and level of secretion were statistically reduced. After
      surgery only 21.7% of the children were capable of oral intake exclusively. LTS
      is an effective and safe technique that can be used in children resulting in
      aspiration control in 100% of the patients and without repercussions in the
      respiratory secretion and pulmonary infections.

PMID- 17216392
TI  - The effects of VitalStim on clinical and research thinking in dysphagia.

PMID- 17216393
TI  - Cardiac regeneration by resident stem and progenitor cells in the adult heart.
AB  - Two main pieces of data have created a new field in cardiac research. First, the
      traditional view on the heart as a postmitotic organ has been challenged by the
      finding of small dividing cells in the heart expressing cardiac contractile
      proteins with stem cell properties and, second, cellular therapy of the diseased
      heart using a variety of different cells has shown encouraging effects on cardiac
      function. These findings immediately raise questions like "what is the identity
      and origin of the cardiac progenitor cells?","which molecular factors are
      involved in their mobilization and differentiation?", and "can these cells repair
      the damaged heart?" This review will address the state of current answers to
      these questions. Emerging evidence suggests that several subpopulations of
      cardiac stem or progenitor cells (CPCs) reside within the adult heart. CPCs with
      the ability to differentiate into all the constituent cells in the adult heart
      including cardiac myocytes, vascular smooth muscle and endothelial cells have
      been identified. Valuable knowledge has been obtained from the large number of
      animal studies and a number of small clinical trials that have utilized a variety
      of adult stem cells for regenerating infarcted hearts. However, contradictory
      reports on the regenerative potential of the CPCs exist, and the mechanisms
      behind the reported hemodynamic effects are intensely debated. Besides directly
      replenishing cardiac tissue, CPCs could also function by stimulating angiogenesis
      and improving survival of existing cells by secretion of paracrine factors. With
      this review we suggest that a better understanding of CPC biology will be pivotal
      for progressing therapeutic cardiac regeneration. This includes an extended
      knowledge of the molecular mechanisms behind their mobilization, differentiation,
      survival and integration in the myocardium.

PMID- 17216396
TI  - New developments and technologies in dermatology.

PMID- 17216395
TI  - Laparoscopically assisted components separation technique for ventral incisional
      hernia repair.
AB  - Reconstruction of the abdominal wall to repair ventral hernias continues to pose
      a challenge to surgeons due to relatively high rates of recurrence and morbidity.
      In 1990, Ramirez pioneered a technique of components separation of the abdominal
      wall for ventral hernia repair. Although an effective hernia repair, the
      mobilization of skin and subcutaneous tissue endangers the blood supply and
      predisposes midline skin to necrosis. The goal of this study is to determine
      whether releasing incisions in the transversus abdominis fascia and posterior
      rectus sheath provide adequate mobilization of the abdominal wall necessary for
      ventral hernia repair, thus paving the way for a laparoscopic component
      separation technique. Ten fresh cadavers were used and one side of the abdomen
      underwent the conventional Ramirez components separation: midline incision,
      dissection of skin and subcutaneous tissue off the anterior abdominal wall, and
      incisions in the external oblique aponeurosis and posterior rectus sheath, while
      the other side received incisions in the transversus abdominis fascia and the
      posterior rectus sheath with no undermining of the skin. The amount of fascial
      translation was measured after each incision. Incising only the external oblique
      aponeurosis produced greater mobilization of the abdominal wall at the level of
      the umbilicus (P = 0.02) and anterior superior iliac spine (ASIS, P = 0.029) than
      releasing only transversus abdominis fascia. More importantly, there was no
      statistically significant difference in the amount of release produced by the
      complete internal-release components separation versus the conventional
      technique. In order to test the feasibility of performing the procedure
      laparoscopically, one additional cadaver underwent a laparoscopic transversus
      abdominis fascia release. The procedure was successful and resulted in comparable
      amounts of fascial release as the other 10 cadavers. From this study, it appears
      technically feasible to perform a laparoscopic components separation to repair a
      ventral hernia and the procedure produces the same amount of release as the
      conventional open component separation technique.

PMID- 17216397
TI  - Increased fluoride uptake in human dental specimens treated with diode laser.
AB  - The hypothesis of this study was the fact that diode lasers can increase the
      fluoride uptake in dental structures. The main objectives were: (1) to evaluate
      the effect of diode laser-NaF varnish combination on binding fluoride to dental
      enamel in an in vitro model and (2) to analyse outer enamel surface changes
      produced by the laser energy. After NaF enamel varnish and laser irradiation at
      different levels of energy, specimen surfaces were examined by environmental
      scanning electron microscopy. The incorporation of F(-) ion into the dental
      structure was quantitatively determined by using a fluoride ion-selective
      electrode. Results showed that the laser treatment significantly increased the
      binding of fluoride to the enamel surface without damaging it. The amount of F(-)
      estimated was 37 +/- 7 mg/l to the power of 5 W and 58 +/- 12 mg/l to the power
      of 7 W. These increases were significantly greater than the ones achieved by
      conventional topical fluoridation. The results were analysed and compared by
      Kruskal-Wallis and Dunn's multiple comparison tests, and significant statistical
      differences were found. These suggest that the NaF varnish-diode laser
      combination may be a useful option for the effective fluoridation of teeth.

PMID- 17216398
TI  - Analgesic activity of a polysaccharide in experimental osteoarthritis in rats.
AB  - Viscosupplementation efficacy has been related to the high molecular weight of
      hyaluronic acid-like compounds, as well as to gel formulation. We evaluated the
      effect of a galactomannan polysaccharide derived from Guar gum (GG) in joint pain
      in an osteoarthritis (OA) model. Wistar rats (six animals/group) were subjected
      to anterior cruciate ligament transection (ACLT-OA group). The OA group was
      compared to a false-operated group (sham). Joint pain was recorded daily, using
      the articular incapacitation test, until 7 days after ACLT. Solutions or gel
      preparations of GG (100 microg) or Hylan G-F 20 (100 microg), used as a
      comparator, were given intraarticularly (i.a.) at day 4 after ACLT. Controls
      received saline i.a. The OA group had significantly increased joint pain as
      compared to sham (P<0.001). GG, either as a gel or solution, significantly
      inhibited joint pain similar to the inhibition achieved with Hylan G-F20. This is
      the first demonstration that a galactomannan derived from GG reduces joint pain
      in experimental OA. This analgesia is independent of the colloidal state. We
      propose that the analgesic benefit of viscosupplementation may be due to an
      intrinsic carbohydrate-mediated mechanism rather than to the rheologic properties
      of the material.

PMID- 17216399
TI  - Efficacy of Farabloc as an analgesic in primary fibromyalgia.
AB  - The goal of our study was to determine the efficacy of Farabloc, an
      electromagnetic shielding fabric compared to placebo fabric when worn as a
      nightgown, as an analgesic in patients hospitalized with fibromyalgia. In a
      rheumatologic and rehabilitation hospital, we performed a phase 1, single-blind
      study of patients using Farabloc (F) or placebo (P) gowns for 8 h per night
      during the 20-day hospitalization and a phase 2, single-blind crossover study of
      patients using both F and P gowns randomly and alternatively switching after 10
      of 21 days hospitalization (phase 1: 42 F, mean age 49.02 years, 35 female, 7
      male; 84 P, mean age 48.08 years, 72 female, 12 males; phase 2: 25 F/P, P/F, or
      P/P, mean age 44.0 years, 24 female, 1 male). The study involved randomly
      selected and blinded use of hospital gown 8 h per night of either F or P fabric.
      The main outcome measures were changes from admission or midpoint to discharge in
      quantity of pain (QN), quality of pain (QL), and paracetamol use (PU). In phase
      1, all three variables significantly favored F over P when using paired t test,
      two sample t test, Mann-Whitney, and analysis of covariance tests. QN was reduced
      (F = -2.03 -/+ 0.99*, P = 0.59 -/+ 0.71). QL was reduced (F = -10.64 -/+ 5.69*, P
      = -2.54 -/+ 3.40). PU was reduced (F = 10.69 -/+ 6.68*, P = 26.12 -/+ 9.37). In
      phase 2, comparing midpoint to discharge levels in the three variables again
      favored P/F over F/P and P/P (>0.001): QN (P/F +16.00 -/+ 8.35* F/P -13.27 -/+
      11.40), QL (P/F +8.71 -/+ 4.75* F/P -6.55 -/+ 5.59), and PU (F -9.29 -/+ 4.39* P 
      18.00 -/+ 5.27) (*p = <0.001). Patients with fibromyalgia had less pain after
      sleeping in a gown made of Farabloc than with a placebo fabric. This suggests
      that Farabloc, an electromagnetic shielding fabric, has analgesic properties in
      fibromyalgia. Reduced pain observation is consistent with previous studies in
      phantom limb pain and delayed onset muscle pain. Limitations of this study
      include single blind design, small sample size, and in phase 2, a lack of washout
      period and a F/F group.

PMID- 17216401
TI  - Maturation of [NiFe]-hydrogenases in Escherichia coli.
AB  - Hydrogenases catalyze the reversible oxidation of dihydrogen. Catalysis occurs at
      bimetallic active sites that contain either nickel and iron or only iron and the
      nature of these active sites forms the basis of categorizing the enzymes into
      three classes, the [NiFe]-hydrogenases, the [FeFe]-hydrogenases and the iron
      sulfur cluster-free [Fe]-hydrogenases. The [NiFe]-hydrogenases and the [FeFe]
      hydrogenases are unrelated at the amino acid sequence level but the active sites
      share the unusual feature of having diatomic ligands associated with the Fe atoms
      in the these enzymes. Combined structural and spectroscopic studies of [NiFe]
      hydrogenases identified these diatomic ligands as CN- and CO groups. Major
      advances in our understanding of the biosynthesis of these ligands have been
      achieved primarily through the study of the membrane-associated [NiFe]
      hydrogenases of Escherichia coli. A complex biosynthetic machinery is involved in
      synthesis and attachment of these ligands to the iron atom, insertion of the
      Fe(CN)2CO group into the apo-hydrogenase, introduction of the nickel atom into
      the pre-formed active site and ensuring that the holoenzyme is correctly folded
      prior to delivery to the membrane. Although much remains to be uncovered
      regarding each of the individual biochemical steps on the pathway to synthesis of
      a fully functional enzyme, our understanding of the initial steps in CN-
      synthesis have revealed that it is generated from carbamoyl phosphate. What is
      becoming increasingly clear is that the metabolic origins of the carbonyl group
      may be different.

PMID- 17216400
TI  - A structural comparison of human serum transferrin and human lactoferrin.
AB  - The transferrins are a family of proteins that bind free iron in the blood and
      bodily fluids. Serum transferrins function to deliver iron to cells via a
      receptor-mediated endocytotic process as well as to remove toxic free iron from
      the blood and to provide an anti-bacterial, low-iron environment. Lactoferrins
      (found in bodily secretions such as milk) are only known to have an anti
      bacterial function, via their ability to tightly bind free iron even at low pH,
      and have no known transport function. Though these proteins keep the level of
      free iron low, pathogenic bacteria are able to thrive by obtaining iron from
      their host via expression of outer membrane proteins that can bind to and remove
      iron from host proteins, including both serum transferrin and lactoferrin.
      Furthermore, even though human serum transferrin and lactoferrin are quite
      similar in sequence and structure, and coordinate iron in the same manner, they
      differ in their affinities for iron as well as their receptor binding properties:
      the human transferrin receptor only binds serum transferrin, and two distinct
      bacterial transport systems are used to capture iron from serum transferrin and
      lactoferrin. Comparison of the recently solved crystal structure of iron-free
      human serum transferrin to that of human lactoferrin provides insight into these
      differences.

PMID- 17216402
TI  - Simulations of chemotaxis and random motility in 2D random porous domains.
AB  - We discuss a generic computational model of eukariotic chemotaxis in 2D random
      porous domains. The model couples the fully time-dependent finite-difference
      solution of a reaction-diffusion equation for the concentration field of a
      chemoattractant to biased random walks representing individual chemotactic cells.
      We focus in particular on the influence of consumption of chemoattractant by the
      boundaries of obstacles with irregular shapes which are distributed randomly in
      the domain on the chemotactic response of the cells. Cells are stimulated to
      traverse a field of obstacles by a line source of chemoattractant. We find that
      the reactivity of the obstacle boundaries with respect to the chemoattractant
      strongly determines the transit time of cells through two primary mechanisms. The
      channeling effect arises because cells are effectively repelled from surfaces
      which consume chemoattractant, and opposing surfaces therefore act to keep cells
      in the middle of channels. This reduces traversal times relative to the case with
      unreactive boundaries, provided that the appropriate Peclet number relating the
      strength of reactivity to diffusion in governing chemoattractant transport is
      neither too low nor too high. The dead-zone effect arises due to a realistic
      threshold on the chemotactic response, which at steady state results in portions
      of the domain having no detectable gradient. Of these two, the channeling effect
      is responsible for 90% of the sensitivity of transit times to boundary
      reactivity. Based on these results, we speculate that it may be possible to tune
      the rates of cellular penetration into porous domains by engineering the
      reactivity of the internal surfaces to cytokines.

PMID- 17216403
TI  - Generalized, switch-like competitive heterodimerization networks.
AB  - High-dimensional switches have been proposed as a way to model cellular
      differentiation, particularly in the context of basic Helix-Loop-Helix (bHLH)
      competitive heterodimerization networks. A previous study derived a simple rule
      showing how many elements can be co-expressed, depending on the rate of
      competition within the network. A limitation to that rule, however, is that many
      biochemical parameters were considered to be identical. Here, we derive a
      generalized rule. This in turns allows one to study more ways in which these
      networks could be regulated, linking intrinsic cellular differentiation
      determinants to extracellular cues.

PMID- 17216407
TI  - The World Federation of Interventional and Therapeutic Neuroradiology.

PMID- 17216404
TI  - Intermittent dysphagia for solids associated with a multiringed esophagus:
      clinical features and response to dilatation.
AB  - The entity of the multiringed esophagus, generally presenting in adults as
      intermittent dysphagia for solids, is relatively uncommon and its pathogenesis is
      unknown. The goal of this study was to describe the demographic, clinical, and
      endoscopic features of patients presenting with this condition, their response to
      esophageal dilatation, and the relationship of multiple esophageal rings to
      eosinophilic esophagitis. Between 1989 and June 2004, 32 patients at this adult
      hospital fulfilled the following inclusion criteria: (1) intermittent dysphagia
      for solids, (2) multiple esophageal rings at endoscopy, and (3) esophageal
      dilatation(s) performed. Response to esophageal dilatation was measured by need
      for subsequent dilatations. Seventy-five percent of the patients were male.
      Median age at onset of dysphagia was 21 years and at presentation 36.5 years. All
      had multiple rings in the proximal or midesophagus on endoscopy and had undergone
      a total of 73 esophageal dilatations with no esophageal perforations. Median
      maximal dilator size was 15 mm; however, 16% developed significant esophageal
      mucosal tears even with 11-mm dilators. Sixty-six percent required repeat
      dilatation, with the median time interval before recurrence being 8 months.
      Eosinophilic esophagitis (mucosal eosinophil count > 20/HPF) was present in 50%
      of this cohort. From this study we conclude that a multiringed esophagus causing
      intermittent dysphagia occurs predominantly in young males, responds well to
      dilatation, but repeated dilatations are often necessary. Dilatation can lead to
      extensive mucosal tears and should be performed with caution. Eosinophilic
      esophagitis is commonly but not invariably associated with this entity. Frequent
      relapse of dysphagia highlights the need for effective pharmacotherapy.

PMID- 17216408
TI  - Vascular anomalies of the medulla oblongata.

PMID- 17216409
TI  - Benign fibrous histiocytoma of the pterygopalatine fossa with intracranial
      extension.

PMID- 17216412
TI  - Characterising error-awareness of attentional lapses and inhibitory control
      failures in patients with traumatic brain injury.
AB  - Awareness deficits are a significant problem following traumatic brain injury
      (TBI). This study examined error processing as candidate marker of awareness and
      compared the performance of 18 TBI participants and 18 controls using an online
      error-monitoring task while participants performed simple go/no-go tasks. Error
      monitoring performance was compared where the no-go target was part of (a) a
      predictive sequence, (b) predictive sequence plus a dual-task element and (c) a
      random sequence. Results showed that the TBI participants, in contrast to control
      participants, were significantly impaired at monitoring their errors during both
      predictive sequence tasks but were not impaired on the random sequence task.
      These findings suggest that following TBI, when an error is more impulsive it may
      be more easily monitored, whereas when an error is characterised by attentional
      drift, subsequent error-processing mechanisms may fail to engage. Higher levels
      of online error-awareness were also associated with lower levels of anxiety,
      fewer symptoms of frontal dysfunction and greater competence in everyday
      functioning.

PMID- 17216413
TI  - rTMS over the intraparietal sulcus disrupts numerosity processing.
AB  - It has been widely argued that the intraparietal sulcus (IPS) is involved in
      tasks that evoke representations of numerical magnitude, among other cognitive
      functions. However, the causal role of this parietal region in processing
      symbolic and non-symbolic numerosity has not been established. The current study
      used repetitive Transcranial Magnetic Stimulation (rTMS) to the left and right
      IPS to investigate the effects of temporary deactivations of these regions on the
      capacity to represent symbolic (Arabic numbers) and non-symbolic (arrays of dots)
      numerosities. We found that comparisons of both symbolic and non-symbolic
      numerosities were impaired after rTMS to the left IPS but enhanced by rTMS to the
      right IPS. A signature effect of numerical distance was also found: greater
      impairment (or lesser facilitation) when comparing numerosities of similar
      magnitude. The reverse pattern of impairment and enhancement was found in a
      control task that required judging an analogue stimulus property (ellipse
      orientation) but no numerosity judgements. No rTMS effects for the numerosity
      tasks were found when stimulating an area adjacent but distinct from the IPS, the
      left and right angular gyrus. These data suggest that left IPS is critical for
      processing symbolic and non-symbolic numerosity; this processing may thus depend
      on common neural mechanisms, which are distinct from mechanisms supporting the
      processing of analogue stimulus properties.

PMID- 17216416
TI  - [Signal reception and processing by the retina].
AB  - Phototransduction occurs in the retina, which, as an outsourced part of the
      brain, fulfills important tasks in neuronal processing for image analysis
      relevant to perception. Interlinked biochemical cycles with immense amplification
      factors transform the electromagnetic waves of light into neuronal activity, and
      photochemical adaptation allows adjustment to light intensities of over more than
      10 logarithmic units. Beginning with its dual system of photoreceptors with
      highly sensible rods and a color sensitive cone system, the retina, with between
      50 and 100 main cell types, is characterized by complex neuronal circuits. The
      resulting center-surround antagonism of the receptive fields serves, amongst
      other things, to amplify intensity and color contrasts. Specialized ganglion cell
      types give rise to parallel signaling pathways into the higher visual centers of
      the brain.

PMID- 17216415
TI  - [Chlamydial diseases of the eye. A short overview].
AB  - In this short review, new data on the taxonomy of Chlamydia and the association
      of these pathogens with various ocular diseases are presented. Clinical diagnosis
      and laboratory tests for ocular C. trachomatis infection are discussed. The
      actual therapy consists in oral azithromycin.

PMID- 17216414
TI  - [Therapy and prognosis of bacterial keratitis].
AB  - This review discusses the current therapy for bacterial keratitis, especially
      that using quinolones of the fourth generation. In addition, the importance of
      additive steroids is discussed. Steroids should be administered at a low dose and
      tapered off slowly, whereas antibiotics should be applied at a high dosage and
      discontinued abruptly.

PMID- 17216417
TI  - [40% Glucose eyedrops for corneal oedema. A rare side-effect].

PMID- 17216418
TI  - [Revision of the recommendations of the Commission on Pharmacotherapy of the
      German Society for Rheumatology. Comment on the use of mycophenolic acid for
      systemic lupus erythematosus].
AB  - According to the NIH scheme, the "evidence based medicine" standard in the
      treatment of severe proliferative lupus-nephritis is cyclophosphamide in
      combination with steroids. Undesired effects, therapy resistance, and deficient
      long-term effects underscore the necessity for the development of alternative
      therapies for the treatment of organ involvement. Mycophenolate mofetil (MMF)
      possesses the potential to decisively improve the therapeutic possibilities for
      systemic lupus erythematosus (SLE). On the basis of the available data, MMF
      represents an alternative to the current standard therapies for severe lupus
      nephritises and shows less toxicity. MMF is also effective in patients with other
      manifestations refractory to conventional therapy. Questions remain unanswered on
      the optimal dosage and possible reduction in cases of remission. In addition, the
      duration of maintenance therapy is unclear. Therefore, large, prospective,
      randomized clinical studies in the treatment of lupus-nephritis with a
      sufficiently long follow-up phase are underway.

PMID- 17216419
TI  - Nf1 expression is dependent on strain background: implications for tumor
      suppressor haploinsufficiency studies.
AB  - Neurofibromatosis type 1 (NF1) is the most common cancer predisposition syndrome
      affecting the nervous system, with elevated risk for both astrocytoma and
      peripheral nerve sheath tumors. NF1 is caused by a germline mutation in the NF1
      gene, with tumors showing loss of the wild type copy of NF1. In addition, NF1
      heterozygosity in surrounding stroma is important for tumor formation, suggesting
      an additional role of haploinsufficiency for NF1. Studies in mouse models and NF1
      families have implicated modifier genes unlinked to NF1 in the severity of the
      disease and in susceptibility to astrocytoma and peripheral nerve sheath tumors.
      To determine if differences in Nf1 expression may contribute to the strain
      specific effects on tumor predisposition, we examined the levels of Nf1 gene
      expression in mouse strains with differences in tumor susceptibility using
      quantitative polymerase chain reaction. The data presented in this paper
      demonstrate that strain background has as much effect on Nf1 expression levels as
      mutation of one Nf1 allele, indicating that studies of haploinsufficiency must be
      carefully interpreted with respect to strain background. Because expression
      levels do not correlate entirely with the susceptibility or resistance to tumors
      observed in the strain, these data suggest that either variation in Nf1 levels is
      not responsible for the differences in astrocytoma and peripheral nerve sheath
      tumor susceptibility in Nf1-/+;Trp53-/+cis mice, or that certain mouse strains
      have evolved compensatory mechanisms for differences in Nf1 expression.

PMID- 17216420
TI  - Safety and tolerability of clarithromycin administered to children at higher-than
      recommended doses.
AB  - A tendency among pediatricians in Greece to use higher-than-recommended doses of
      clarithromycin was noted over several years, prompting this study of the safety
      and tolerability of this macrolide in 343 children over a period of 9 months. The
      study group comprised nonhospitalized patients of 29 pediatricians practicing in
      Athens. All were prescribed clarithromycin for upper respiratory (n = 257) or
      lower respiratory tract infection (n = 78). Overall, 77.8% were treated with
      doses that exceeded the recommended dose of 15 mg/kg/day, and 26% received doses
      of > or = 30 mg/kg/day (median dose, 20 mg/kg/day). The tolerability of
      clarithromycin was judged as "very good" in 75% of the children, as "good" in
      16%, and as "moderate" in 5%, whereas intolerability was observed in 4% of the
      cases. Adverse reactions, mainly gastrointestinal in nature, were reported in
      17.5% of the cases. With regard to both tolerability and adverse events recorded,
      there were no statistically significant differences between the group of patients
      who received the recommended dose and the group who received higher doses.
      Clarithromycin continues to present a safe and well-tolerated profile for the
      treatment of common pediatric infections, even when administered at higher-than
      recommended doses. Whether it is more efficacious in this setting is a matter for
      further study.

PMID- 17216422
TI  - Human bocavirus DNA detected by quantitative real-time PCR in two children
      hospitalized for lower respiratory tract infection.

PMID- 17216421
TI  - Lack of microbial DNA in tissue specimens of patients with abdominal aortic
      aneurysms and positive Chlamydiales serology.
AB  - In a case-control study that included a total of 98 patients and 83 controls, the
      possible link between various pathogens and abdominal aortic aneurysms was
      investigated. For 68 patients with abdominal aortic aneurysm and age-matched
      controls, no differences were detected in the levels of immunoglobulin (Ig)A and
      IgG Chlamydiaceae and Chlamydophila pneumoniae antibodies. Patients with IgA
      titers positive for Chlamydophila pneumoniae showed progressive disease (defined
      as an annual increase of the aneurysm diameter of > or = 0.5 cm) more frequently
      than patients with negative IgA titers (p = 0.046). Polymerase chain reactions
      performed to detect DNA for Chlamydophila pneumoniae, Chlamydia trachomatis,
      Chlamydophila psittaci, human cytomegalovirus, Borrelia burgdorferi and
      Helicobacter pylori in tissue specimens of 30 patients and 15 controls were
      negative. In summary, Chlamydophila pneumoniae may contribute to aortic aneurysm
      disease progression, but DNA of this and other pathogens was not found in
      patients' specimens.

PMID- 17216424
TI  - Cost of breast cancer in Sweden in 2002.
AB  - Breast cancer is the most common cancer among Swedish women and an important
      cause of illness and death. The aim of this study was to estimate the total cost
      of breast cancer in Sweden in 2002, using a top-down prevalence-based cost-of
      illness approach. The total cost of breast cancer in Sweden in 2002 was estimated
      at 3.0 billion SEK (1 euro = 9.4 SEK). The direct costs were estimated at 895
      million SEK and constituted 30% of the total cost. Indirect costs were estimated
      at 2.1 billion SEK and constituted 70% of the total cost. The main cost driver
      was production losses caused by premature mortality, amounting to 52% of the
      indirect costs. The reason that indirect costs were the dominant cost is because
      most newly detected breast cancers occur in patients aged below 65, thus causing
      significant production losses due to sick leave, early retirement, and premature
      mortality.

PMID- 17216423
TI  - Penetration of levofloxacin into the anterior chamber (aqueous humour) of the
      human eye after intravenous administration.
AB  - In the study presented here, levofloxacin concentrations in serum samples and the
      aqueous humour (AH) of 16 patients undergoing cataract extraction were measured
      in order to determine the penetration characteristics of levofloxacin into the AH
      of the non-inflamed human eye. Cataract removal was performed at various times
      (from 90 to 270 min) after the end of a 30-min intravenous infusion of 500 mg of
      levofloxacin. Serum samples were obtained 1 h after the end of levofloxacin
      administration (Cmax); AH and a second serum sample were taken simultaneously
      during the operation, and the concentrations of levofloxacin in AH (C(AH)) and
      serum (C(S)) were determined using a rapid high-performance liquid chromatography
      assay. The mean Cmax was 6.07 microg/ml (range 3.75-9.53 microg/ml, SD 1.83). The
      mean C(AH) at the first hour following levofloxacin administration was 1.37
      microg/ml (range 1.17-1.6 microg/ml, SD 0.22) and the mean ratio (R=C(AH)/C(S))
      was 0.26 (range 0.24-0.3, SD 0.02). The mean C(AH) at 125-270 min following
      levofloxacin administration was 1.39 microg/ml (range 0.82-1.98 microg/ml, SD
      0.33) and the mean R was 0.3 (range 0.15-0.53, SD 0.11). Of 16 patients, 15 had a
      C(AH) of >1 microg/ml 1 h after levofloxacin administration. In conclusion, 1 h
      after administration of 500 mg of levofloxacin, the levels obtained were higher
      than the MIC at which 90% of methicillin-susceptible Staphylococcus aureus and
      certain gram-negative bacteria strains are inhibited.

PMID- 17216425
TI  - Incorporating efficiency in hospital-capacity planning in Germany.
AB  - Hospital occupancy is a key metric in hospital-capacity planning in Germany, even
      though this metric neglects important drivers of economic efficiency, for example
      treatment costs and case mix. We suggest an alternative metric, which
      incorporates economic efficiency explicitly, and illustrate how this metric can
      be used in the hospital-capacity planning cycle. The practical setting of this
      study is the hospital capacity planning process in the German federal state of
      Rheinland-Pfalz. The planning process involves all 92 acute-care hospitals of
      this federal state. The study is based on standard hospital data, including
      annual costs, number of cases--disaggregated by medical departments and ICD
      codes, respectively--length-of-stay, certified beds, and occupancy rates. Using
      the developed metric, we identified 18 of the 92 hospitals as inefficient and
      targets for over-proportional capacity cuts. On the upside, we identified 15
      efficient hospitals. The developed model and analysis has affected the federal
      state's most recent medium term planning cycle.

PMID- 17216426
TI  - Prenatal cannibalism in an insect.
AB  - Host selection and infection strategies of parasitoids often correlate with high
      parental investment and low numbers of progeny. In this study, we investigate how
      additional internal mechanisms might shape brood size and fitness of the
      offspring. Emblemasoma auditrix is a parasitoid fly in which about 38 larvae
      hatch simultaneously in utero. After host location, a single larva is deposited
      into the host, where it rapidly develops and pupates after about 5 days. The
      search for hosts can take several weeks, and during that time, the larvae arrest
      their development and remain in the first larval instar. Nevertheless, the larvae
      increase in weight within the uterus, and this growth correlates to a decrease in
      the number of larvae, although no larvae are deposited. Thus, our data indicate a
      first case of prenatal cannibalism in an invertebrate with larvae feeding on each
      other within the uterus of the adult.

PMID- 17216427
TI  - Biomimetics and the case of the remarkable ragworms.
AB  - Biomimetics is a rapidly growing field both as an academic and as an applied
      discipline. This paper gives a short introduction to the current status of the
      discipline before it describes three approaches to biomimetics: the mechanism
      driven, which is based on the study of a specific mechanism; the focused organism
      driven, which is based on the study of one function in a model organism; and the
      integrative organism-driven approach, where multiple functions of a model
      organism provide inspiration. The first two are established approaches and
      include many modern studies and the famous biomimetic discoveries of Velcro and
      the Lotus-Effect, whereas the last approach is not yet well recognized. The
      advantages of the integrative organism-driven approach are discussed using the
      ragworms as a case study. A morphological and locomotory study of these marine
      polychaetes reveals their biomimetic potential, which includes using their
      ability to move in slippery substrates as inspiration for novel endoscopes, using
      their compound setae as models for passive friction structures and using their
      three gaits, slow crawling, fast crawling, and swimming as well as their rapid
      burrowing technique to provide inspiration for the design of displacement pumps
      and multifunctional robots.

PMID- 17216428
TI  - Male satin bowerbirds (Ptilonorhynchus violaceus) compensate for sexual signal
      loss by enhancing multiple display features.
AB  - Numerous studies have focussed on the relationship between female choice and the
      multiple exaggerated sexual traits of males. However, little is known about the
      ability of males to actively enhance specific components of their display in
      response to the loss of one component. We investigated the capacity of male satin
      bowerbirds (Ptilonorhynchus violaceus) to respond to the loss of one of their
      sexual signals by performing an experiment in which we removed decorations at
      their bowers. We found that males compensated for decoration loss by increasing
      bower construction behaviour and decreasing their latency to bower painting.
      These results are novel because they suggest that males can assess the quality of
      their own display and make decisions about how to augment their displays. We
      discuss these results in the context of previous studies of mate choice in satin
      bowerbirds, as both of the supplementary behaviours we observed are known
      correlates of male mating success.

PMID- 17216429
TI  - Fossil insect evidence for the end of the Western Settlement in Norse Greenland.
AB  - The fate of Norse farming settlements in southwest Greenland has often been seen
      as one of the great mysteries of North Atlantic colonization and expansion.
      Preservation of organic remains in the permafrost of the area of the Western
      Settlement, inland from the modern capital Nuuk, allowed very detailed study of
      the phases of occupation. Samples were taken from house floors and middens during
      the process of archaeological excavations and from insect remains were abstracted
      and identified in the laboratory. In this study, we present a new paleoecological
      approach principally examining the fossil fly faunas from house floors. The
      results of our study provide contrasting detailed pictures of the demise of two
      neighboring farms, Garden under Sandet and Nipaatsoq, one where abandonment
      appears as part of a normal process of site selection and desertion, and the
      other where the end was more traumatic. The level of detail, which was obtained
      by analysis of the dipterous (true fly) remains, exceeds all previous work and
      provides insights otherwise unobtainable.

PMID- 17216431
TI  - OECD validation of the rodent Hershberger assay using three reference chemicals;
      17alpha-methyltestosterone, procymidone, and p,p'-DDE.
AB  - The rodent Hershberger assay is being validated as an in vivo test method for
      detecting androgenic or antiandrogenic compounds by the Organization for Economic
      Cooperation and Development (OECD). As part of the international validation work,
      we studied 17alpha-methyltestosterone for evaluating androgenic activity, and
      procymidone and p,p'-DDE for evaluating antiandrogenic activity. Male Sprague
      Dawley rats were castrated at postnatal day 42, and only the rats that showed
      preputial separation were used in this study. Seven days after castration,
      chemicals were administered daily by gavages to groups of rats for 10 days, as
      recommended by OECD phase-2 protocol. Administration of 17alpha
      methyltestosterone induced increases of weights of accessory sex tissues and
      glands in a dose-dependent manner. Administration of procymidone and p,p'-DDE
      produced a dose-dependent decrease of weights of accessory sex tissues and glands
      in the rats co-treated with testosterone propionate (0.4 mg/kg/day)
      subcutaneously. Our data strongly suggested that the current protocol of OECD
      Hershberger assay (phase-2) should be used as a reliable method for the detection
      of endocrine related toxicity of other chemicals.

PMID- 17216430
TI  - Enzymatic production of biosilica glass using enzymes from sponges: basic aspects
      and application in nanobiotechnology (material sciences and medicine).
AB  - Biomineralization, biosilicification in particular (i.e. the formation of
      biogenic silica, SiO2), has become an exciting source of inspiration for the
      development of novel bionic approaches following "nature as model". Siliceous
      sponges are unique among silica forming organisms in their ability to catalyze
      silica formation using a specific enzyme termed silicatein. In this study, we
      review the present state of knowledge on silicatein-mediated "biosilica"
      formation in marine sponges, the involvement of further molecules in silica
      metabolism and their potential application in nanobiotechnology and medicine.

PMID- 17216432
TI  - Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state
      unbalance, impairment of energetic metabolism and apoptosis in rat kidney
      mitochondria.
AB  - The clinical use of cisplatin (cis-diamminedichloroplatinum II) is highly limited
      by its nephrotoxicity. The precise mechanisms involved in cisplatin-induced
      mitochondrial dysfunction in kidney have not been completely clarified.
      Therefore, we investigated in vivo the effects of cisplatin on mitochondrial
      bioenergetics, redox state, and oxidative stress as well as the occurrence of
      cell death by apoptosis in cisplatin-treated rat kidney. Adult male Wistar rats
      weighing 200-220 g were divided into two groups. The control group (n = 8) was
      treated only with an intraperitoneal (i.p.) injection of saline solution (1 ml
      per 100 g body weight), and the cisplatin group (n = 8) was given a single
      injection of cisplatin (10 mg/kg body weight, i.p.). Animals were sacrificed 72 h
      after the treatment. The cisplatin group presented acute renal failure
      characterized by increased plasmatic creatinine and urea levels. Mitochondrial
      dysfunction was evidenced by the decline in membrane electrochemical potential
      and the substantial decrease in mitochondrial calcium uptake. The mitochondrial
      antioxidant defense system was depleted, as shown by decreased GSH and NADPH
      levels, GSH/GSSG ratio, and increased GSSG level. Moreover, cisplatin induced
      oxidative damage to mitochondrial lipids, including cardiolipin, and oxidation of
      mitochondrial proteins, as demonstrated by the significant decrease of sulfhydryl
      protein concentrations and increased levels of carbonylated proteins.
      Additionally, aconitase activity, which is essential for mitochondrial function,
      was also found to be lower in the cisplatin group. Renal cell death via apoptosis
      was evidenced by the increased caspase-3 activity. Results show the central role
      of mitochondria and the intensification of apoptosis in cisplatin-induced acute
      renal failure, highlighting a number of steps that might be targeted to minimize
      cisplatin-induced nephrotoxicity.

PMID- 17216433
TI  - Protective effects of magnolol against oxidized LDL-induced apoptosis in
      endothelial cells.
AB  - Magnolol, a compound extracted from the Chinese medicinal herb Magnolia
      officinalis, has several biological effects. However, its protective effects
      against endothelial injury remain unclear. In this study, we examined whether
      magnolol prevents oxidized low density lipoprotein (oxLDL)-induced vascular
      endothelial apoptosis. Incubation of oxLDL with magnolol (2.5-20 microM)
      inhibited copper-induced oxidative modification via diene formation,
      thiobarbituric acid reactive substances (TBARS) assay and electrophoretic
      mobility assay. Apoptotic cell death as characterized by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) stain. We
      measured the production of reactive oxygen species (ROS) by using the fluorescent
      probe 2',7'-dichlorofluorescein acetoxymethyl ester (DCF-AM), and observed the
      activity of antioxidant enzymes. Furthermore, several apoptotic signaling
      pathways which showed NF-kappaB activation, increased cytosolic calcium,
      alteration of mitochondrial membrane potential, cytochrome c release and
      activation of caspase 3 were also investigated. We demonstrated that magnolol
      prevented the copper-induced oxidative modification of LDL. Magnolol attenuated
      the oxLDL-induced ROS generation and subsequent NF-kappaB activation.
      Furthermore, intracellular calcium accumulation and subsequent mitochondrial
      membrane potential collapse, cytochome c release and activation of caspase 3
      caused by oxLDL were also inhibited by magnolol. Our results suggest that
      magnolol may have clinical implications in the prevention of atherosclerotic
      vascular disease through decreasing the oxLDL-induced ROS production.

PMID- 17216434
TI  - Beta-adrenoceptor blocker treatment and the cardiac beta-adrenoceptor-G
      protein(s)-adenylyl cyclase system in chronic heart failure.
AB  - Recent studies showed that chronic beta-adrenoceptor (AR) blocker treatment
      exerts beneficial effects in patients with chronic heart failure (CHF). In CHF,
      sympathetic drive to the heart is increased, and this causes pathological changes
      in cardiac beta-AR-G-protein(s)-adenylyl cyclase system: Cardiac beta-1 AR are
      decreased, and amount and activity of cardiac G(i)-protein and G-protein-coupled
      receptor kinase (GRK) are increased resulting in diminished cardiac beta-AR
      functional responsiveness. One possible mechanism of beneficial effects of beta
      AR blockers could be that they prevent adverse effects of increased sympathetic
      activity and up-regulate cardiac (and vascular) beta-AR density, and by this,
      enhance beta-AR-mediated effects. Another possibility could be that chronic beta
      AR blocker treatment normalizes activity of G(i)-protein and may thereby restore
      beta-AR functional responsiveness. Moreover, failing human heart exhibits an
      inverse force-frequency relationship. beta-AR blockers reduce heart rate; this
      may, therefore, improve force of contraction. One of the strongest stimuli to
      activate GRK is increased sympathetic activity (as in CHF) via beta-AR
      stimulation. beta-AR blockers, by blocking beta-AR, can prevent GRK activation
      and/or can reduce the (previously enhanced) GRK activity, and this might-at least
      partly-contribute to beneficial effects of beta-AR blockers in CHF treatment.
      Finally, the "loss-of-function" Arg389Gly beta-1 AR polymorphism seems to
      determine heart rate and blood pressure responses to beta-1 AR blocker
      administration: Arg389Arg beta-1 AR subjects exhibit stronger effects than
      subjects with one or two Gly389 alleles. Thus, it might be predicted that
      patients homozygous Arg389 beta-1 AR should be good responders, whereas patients
      homozygous Gly389 beta-1 AR polymorphism should be poor or non-responders.

PMID- 17216435
TI  - Population pharmacokinetics of mefloquine in military personnel for prophylaxis
      against malaria infection during field deployment.
AB  - OBJECTIVE: The purpose of this study was to determine the population
      pharmacokinetics of mefloquine in healthy military personnel during prophylaxis
      for malaria infections. METHODS: The subjects were 1,111 Australian soldiers
      participating in two studies: a randomised double-blinded study (group A, 161
      subjects) and an open-label study (group B, 950 subjects). Following a loading
      dose (250 mg mefloquine base daily, 3 days), subjects received an oral weekly
      maintenance dose of 250 mg over 6 months. Blood was collected after the last
      split loading dose then at weeks 4, 8 and 16 for group A, and at weeks 13 and 26
      for group B. Plasma mefloquine concentrations were measured by high-performance
      liquid chromatography (HPLC). Pharmacokinetic modelling was performed using
      NONMEM. RESULTS: A two-compartment model with inter-occasion variability (IOV)
      for clearance satisfactorily described the pharmacokinetics. Typical values were
      clearance (CL/F, 2.09 l/h), central volume of distribution (V1/F, 528 l),
      absorption rate constant (KA, 0.24 h(-1)), inter-compartmental clearance (Q/F,
      12.5 l/h), peripheral volume of distribution (V2/F, 483 l) and elimination half
      life (t (1/2), 14.0 days). Weight had a positive influence on central volume but
      was insufficient to warrant dosage adjustments. The inter-individual variability
      (coefficient of variation, CV%) for CL/F and V1/F was 24.4% and 29.6%,
      respectively. The IOV for CL/F was 17.8%. The proportional residual error (CV%)
      for groups A and B was 11.5% and 19.5%, respectively, and the additive error
      standard deviation (SD) was 57 ng/ml and 149 ng/ml, respectively. CONCLUSION: The
      typical parameter values were comparable with those estimated in much smaller
      cohorts of healthy subjects and in malaria patients treated with single-dose
      mefloquine. The lower unexplained variability in the blinded study suggested
      these subjects may have been more compliant in taking their medication than
      soldiers in the open-label study.

PMID- 17216436
TI  - Management of potential drug interactions in community pharmacies: a
      questionnaire-based survey in Switzerland.
AB  - OBJECTIVE: To analyze the current drug-interaction management in Swiss community
      pharmacies, with a particular focus on electronic systems, and to compare the
      results with those expressed by German general practitioners in a recent survey.
      METHODS: Data were collected with a postal questionnaire which was randomly sent
      to 500 out of 833 community pharmacies in the German part of Switzerland.
      RESULTS: The response rate was 57.4%, and only 24.7% pharmacists reported that
      they were confronted less than daily with potential drug interactions. Use of
      computer software to identify potential drug interactions was widespread in
      community pharmacies (90.2%), and the software was the primary source of
      information (81.2 +/- 29.6%). The quality of the interaction software was judged
      sensitive (identifying all dangerous interactions) by 80.5 +/- 21.5%, but
      specific (identifying only relevant interactions) by only 38.3 +/- 32%.
      Pharmacists declared a low override rate (14%) of drug interaction alerts,
      although unjustified alerts were reported by 60.6 +/- 33.1%. In contrast to
      general practitioners, pharmacists opted less often for information on the
      mechanism of the interaction, and more frequently for details for dose
      adjustment. Both groups complained about deficient information on non-interacting
      alternatives. CONCLUSION: The information needs of community pharmacists differed
      considerably from general practitioners, and pharmacists were overwhelmed by
      inappropriate alerts because of a lack of specificity of their drug-interaction
      systems. Substantial improvement of drug-interaction software systems is thus
      required at least in two important aspects, the suppression of inappropriate
      alerts and the tailoring to the needs of the user.

PMID- 17216437
TI  - Genotyping and segregation analyses indicate the presence of only two functional
      MIC genes in rhesus macaques.
AB  - MIC molecules are stress-inducible ligands of the activating receptor NKG2D,
      which is expressed on natural killer cells and subsets of T lymphocytes. In
      rhesus macaques (Macaca mulatta), three different MIC sequences (MIC1, MIC2,
      MIC3) have been described that are closely related to but, according to
      phylogenetic analysis, do not represent orthologues of the human MICA and MICB
      genes. Although a single haplotype of the rhesus macaque Mhc (Mamu) has been
      completely sequenced, it remained unknown so far whether these three sequences
      are derived from two or three Mamu-MIC genes. We genotyped a cohort of 115 rhesus
      macaque individuals for the presence of MIC1, MIC2, and MIC3 sequences and
      analysed the segregation in families. All individuals were positive for MIC2,
      whereas only 66.1 and 80.9 % were positive for MIC1 and MIC3, respectively. MIC1
      and MIC3 sequences segregated in offspring, indicating that they behave as
      alleles. Thus, we conclude that two MIC genes are present in the rhesus macaque
      Mhc, which we propose to designate as Mamu-MICA (MIC1 and MIC3) and Mamu-MICB
      (MIC2). "MIC1" and "MIC3" are regarded as divergent allelic lineages of the Mamu
      MICA gene. Mamu-MIC genotyping of DNA of a cohort of 68 experimentally simian
      immunodeficiency virus (SIV)-infected rhesus macaques revealed no significant
      association of either of the two Mamu-MICA allelic lineages with differences in
      progression to AIDS-like symptoms.

PMID- 17216439
TI  - Cloning and identification of novel cellulase genes from uncultured
      microorganisms in rabbit cecum and characterization of the expressed cellulases.
AB  - A metagenomic cosmid library was prepared in Escherichia coli from DNA extracted
      from the contents of rabbit cecum and screened for cellulase activities. Eleven
      independent clones expressing cellulase activities (four endo-beta-1,4-glucanases
      and seven beta-glucosidases) were isolated. Subcloning and sequencing analysis of
      these clones identified 11 cellulase genes; the encoded products of which shared
      less than 50% identities and 70% similarities to cellulases in the databases. All
      four endo-beta-1,4-glucanases and all seven beta-glucosidases, respectively,
      belonged to glycosyl hydrolase family 5 (GHF 5) and family 3 (GHF 3) and formed
      two separate branches in the phylogenetic tree. Ten of the 11 cloned cellulases
      exhibited highest activities at pH 5.5 approximately 7.0 and 40 approximately 55
      degrees C, a condition similar to that in the rabbit cecum. All the four endo
      beta-1,4-glucanases could hydrolyze a wide range of beta-1,4-, beta-1,4/beta-1,3-
      or beta-1,3/beta-1,6-linked polysaccharides. One endo-beta-1, 4-glucanase gene,
      umcel5G, was overexpressed in E. coli, and the purified recombinant enzyme was
      characterized in detail. The enzymes cloned in this work represented at least
      some of the cellulases operating efficiently in the rabbit cecum. This work
      provides the first snapshot on the cellulases produced by bacteria in rabbit
      cecum.

PMID- 17216438
TI  - A gene family of putative immune recognition molecules in the hydroid
      Hydractinia.
AB  - Animal taxa display a wide array of immune-type receptors that differ in their
      specificities, diversity, and mode of evolution. These molecules ensure effective
      recognition of potential pathogens for subsequent neutralization and clearance.
      We have characterized a family of putative immune recognition molecules in the
      colonial hydroid Hydractinia symbiolongicarpus. A complementary DNA fragment with
      high similarity to the sea urchin L: -rhamnose-binding lectin was isolated and
      used to screen 9.5 genome equivalents of a H. symbiolongicarpus bacterial
      artificial chromosome library. One of the resulting 19 positive clones was
      sequenced and revealed the presence of a 5,111-bp gene organized in 13 exons and
      12 introns. The gene was predicted to encode a 726-amino acid secreted modular
      protein composed of a signal peptide, an anonymous serine-rich domain, eight
      thrombospondin type 1 repeats, and a L: -rhamnose-binding lectin domain. The
      molecule was thus termed Rhamnospondin (Rsp). Southern hybridization and sequence
      analyses indicated the presence of a second Rsp gene. The cDNA from both Rsp
      genes was sequenced in 18 individuals, revealing high levels of genetic
      polymorphism. Nucleotide substitutions were distributed throughout the molecule
      and showed a significantly higher number of synonymous substitutions per
      synonymous sites than its nonsynonymous counterparts. Whole-mount in situ
      hybridization and semi-quantitative reverse transcription polymerase chain
      reaction of microorganism-challenged colonies indicated that Rsp molecules were
      specifically and constitutively expressed in the hypostome of gastrozooids'
      mouth. Thus, the combination of (1) comparative analysis on domain composition
      and function, (2) polymorphism, and (3) expression patterns, suggest that Rsp
      genes encode a family of putative immune recognition receptors, which may act by
      binding microorganisms invading the colony through the polyp's mouth.

PMID- 17216440
TI  - Studies on the Pycnoporus sanguineus CCT-4518 laccase purified by hydrophobic
      interaction chromatography.
AB  - A laccase from Pycnoporus sanguineus was purified by two steps using phenyl
      Sepharose columm. A typical procedure provided 54.1-fold purification, with a
      yield of 8.37%, using syringaldazine as substrate. The molecular weight of the
      purified laccase was 69 and 68 kDa as estimated by 12% (w/v) SDS-PAGE gel and by
      gel filtration, respectively. The K (m) values for the substrates ABTS,
      syringaldazine, and guaiacol were 58, 8.3, and 370 muM, respectively. The
      enzyme's pH optimum for syringaldazine was 4.2 and optimal activity was 50
      degrees C. The enzyme showed to be thermostable because when kept at 50 degrees C
      for 24 and 48 h it retained 93 and 76% activity. This laccase was inhibited by L:
      -cysteine, beta-mercaptoethanol, NaN(3), NaF, and HgCl(2).

PMID- 17216441
TI  - Expression of the Escherichia coli pntAB genes encoding a membrane-bound
      transhydrogenase in Corynebacterium glutamicum improves L-lysine formation.
AB  - A critical factor in the biotechnological production of L: -lysine with
      Corynebacterium glutamicum is the sufficient supply of NADPH. The membrane
      integral nicotinamide nucleotide transhydrogenase PntAB of Escherichia coli can
      use the electrochemical proton gradient across the cytoplasmic membrane to drive
      the reduction of NADP(+) via the oxidation of NADH. As C. glutamicum does not
      possess such an enzyme, we expressed the E. coli pntAB genes in the genetically
      defined C. glutamicum lysine-producing strain DM1730, resulting in membrane
      associated transhydrogenase activity of 0.7 U/mg protein. When cultivated in
      minimal medium with 10% (w/v) carbon source, the presence of transhydrogenase
      slightly reduced glucose consumption, whereas the consumption of fructose,
      glucose plus fructose, and, in particular, sucrose was stimulated. Biomass was
      increased by pntAB expression between 10 and 30% on all carbon sources tested.
      Most importantly, the lysine concentration was increased in the presence of
      transhydrogenase by approximately 10% on glucose, approximately 70% on fructose,
      approximately 50% on glucose plus fructose, and even by approximately 300% on
      sucrose. Thus, the presence of a proton-coupled transhydrogenase was shown to be
      an efficient way to improve lysine production by C. glutamicum. In contrast,
      pntAB expression had a negative effect on growth and glutamate production of C.
      glutamicum wild type.

PMID- 17216442
TI  - An alkaline protease from fresh fruiting bodies of the edible mushroom Pleurotus
      citrinopileatus.
AB  - A protease was purified from fresh fruiting bodies of the edible mushroom
      Pleurotus citrinopileatus. The isolation procedure included ion exchange
      chromatography on DEAE-cellulose, CM-cellulose, and Q-Sepharose and fast protein
      liquid chromatography-gel filtration on Superdex 75. The protease was unadsorbed
      on DEAE-cellulose and Q-Sepharose, but adsorbed on CM-cellulose. In sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis, the protease demonstrated a
      single band with a molecular mass of 28 kDa. The protease showed an optimal pH at
      10 and an optimal temperature at 50 degrees C. The activity of the protease was
      not affected by EDTA, indicating that it is not a metalloprotease. The protease
      exhibited a higher activity in the presence of K(+) and Li(+), but its activity
      was potently inhibited by Al(3+), Cu(2+), and Hg(2+) ions. It manifested a K (m)
      of 3.44 mg/ml and a V (max) of 0.139 mg ml(-1) min(-1). It was devoid of
      ribonuclease and antifungal activities.

PMID- 17216444
TI  - Influence of growth medium on cometabolic degradation of polycyclic aromatic
      hydrocarbons by Sphingomonas sp. strain PheB4.
AB  - The influence of growth medium on cometabolic degradation of polycyclic aromatic
      hydrocarbons (PAHs) was investigated when Sphingomonas sp. strain PheB4 isolated
      from surface mangrove sediments was grown in either phenanthrene-containing
      mineral salts medium (PMSM) or nutrient broth (NB). The NB-grown culture
      exhibited a more rapid cometabolic degradation of single and mixed non-growth
      substrate PAHs compared to the PMSM-grown culture. The concentrations of PAH
      metabolites were also lower in NB-grown culture than in PMSM-grown culture,
      suggesting that NB-grown culture removed metabolites at a faster rate,
      particularly, for metabolites produced from cometabolic degradation of a binary
      mixture of PAHs. Cometabolic pathways of single PAH (anthracene, fluorene, or
      fluoranthene) in NB-grown culture showed similarity to that in PMSM-grown
      culture. However, cometabolic pathways of mixed PAHs were more diverse in NB
      grown culture than that in PMSM-grown culture. These results indicated that
      nutrient rich medium was effective in enhancing cometabolic degradation of mixed
      PAHs concomitant with a rapid removal of metabolites, which could be useful for
      the bioremediation of mixed PAHs contaminated sites using Sphingomonas sp. strain
      PheB4.

PMID- 17216443
TI  - Extremely high alkaline protease from a deep-subsurface bacterium, Alkaliphilus
      transvaalensis.
AB  - A new high-alkaline protease (ALTP) was purified to homogeneity from a culture of
      the strictly anaerobic and extremely alkaliphilic Alkaliphilus transvaalensis.
      The molecular mass was 30 kDa on sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The enzyme showed the maximal caseinolytic activity higher than
      pH 12.6 in KCl-NaOH buffer at 40 degrees C. Hydrolysis of the oxidized insulin B
      chain followed by mass spectrometric analysis of the cleaved products revealed
      that as many as 24 of the total 29 peptide bonds are hydrolyzed in a block
      cutting manner, suggesting that ALTP has a widespread proteolytic functions.
      Calcium ion had no effect on the activity and stability of ALTP, unlike known
      subtilisins. The deduced amino acid sequence of the enzyme comprised 279 amino
      acids plus 97 prepropeptide amino acids. The amino acid sequence of mature ALTP
      was confirmed by capillary liquid chromatography coupled to tandem mass
      spectrometry, which was the 93% coverage of the deduced amino acid sequence. The
      mature enzyme showed moderate homology to subtilisin LD1 from the alkaliphilic
      Bacillus sp. strain KSM-LD1 with 64% identity, and both enzymes formed a new
      subcluster at an intermediate position among true subtilisins and high-alkaline
      proteases in a phylogenetic tree of subtilase family A. ALTP is the first high
      alkaline protease reported from a strict anaerobe in this family.

PMID- 17216445
TI  - Glycolytic pathway and hydrogen yield studies of the extreme thermophile
      Caldicellulosiruptor saccharolyticus.
AB  - NMR analysis of (13)C-labelling patterns showed that the Embden-Meyerhof (EM)
      pathway is the main route for glycolysis in the extreme thermophile
      Caldicellulosiruptor saccharolyticus. Glucose fermentation via the EM pathway to
      acetate results in a theoretical yield of 4 mol of hydrogen and 2 mol of acetate
      per mole of glucose. Previously, approximately 70% of the theoretical maximum
      hydrogen yield has been reached in batch fermentations. In this study, hydrogen
      and acetate yields have been determined at different dilution rates during
      continuous cultivation. The yields were dependent on the growth rate. The highest
      hydrogen yields of 82 to 90% of theoretical maximum (3.3 to 3.6 mol H(2) per mol
      glucose) were obtained at low growth rates when a relatively larger part of the
      consumed glucose is used for maintenance. The hydrogen productivity showed the
      opposite effect. Both the specific and the volumetric hydrogen production rates
      were highest at the higher growth rates, reaching values of respectively 30 mmol
      g(-1) h(-1) and 20 mmol l(-1) h(-1). An industrial process for biohydrogen
      production will require a bioreactor design, which enables an optimal mix of high
      productivity and high yield.

PMID- 17216446
TI  - Effect of culture conditions on antifouling compound production of a sponge
      associated fungus.
AB  - Microorganisms associated with invertebrate hosts have long been suggested to be
      a source for bioactive metabolites. In this study, we reported that a sponge
      associated fungus, Letendraea helminthicola, produced two antifouling compounds:
      3-methyl-N-(2-phenylethyl) butanamide and cyclo(D-Pro-D-Phe). To optimize the
      production of these antifouling compounds, we then examined the production of
      compounds under different culture conditions (temperature, salinity, pH, and
      carbon and nitrogen sources). This fungus grew well and produced more compounds
      at temperatures between 18 and 30 degrees C; the fungus grew well at 75 parts per
      thousand (ppt) salinity but produced the highest amount of antifouling compounds
      at 30 and 45 ppt. The optimal initial pH value for mycelial growth was 5.5 to
      6.5, whereas the production of the antifouling compounds was maximized at pH 3.5
      and 4.5. Glucose and xylose (as carbon sources) increased the production of
      antifouling compounds. Yeast extract and peptone (as nitrogen sources) maximized
      the production of mycelial biomass and antifouling compounds. Our results
      indicate that culture conditions greatly affect the production of bioactive
      compounds from mycelial fungal cultures as exemplified by strain L. helminthicola
      and that the conditions favorable for fungal growth may not be the best
      conditions for bioactive compound production.

PMID- 17216447
TI  - Rare carotenoids, (3R)-saproxanthin and (3R,2'S)-myxol, isolated from novel
      marine bacteria (Flavobacteriaceae) and their antioxidative activities.
AB  - We isolated three orange or yellow pigment-producing marine bacteria, strains
      04OKA-13-27 (MBIC08261), 04OKA-17-12 (MBIC08260), and YM6-073 (MBIC06409), off
      the coast of Okinawa Prefecture in Japan. These strains were classified as novel
      species of the family Flavobacteriaceae based on their 16S rRNA gene sequence.
      They were cultured, and the major carotenoids produced were purified by
      chromatographic methods. Their structures were determined by spectral data to be
      (3R)-saproxanthin (strain 04OKA-13-27), (3R,2'S)-myxol (strain YM6-073), and
      (3R,3'R)-zeaxanthin (strains YM6-073 and 04OKA-17-12). Saproxanthin and myxol,
      which are monocyclic carotenoids rarely found in nature, demonstrated significant
      antioxidative activities against lipid peroxidation in the rat brain homogenate
      model and a neuro-protective effect from L-glutamate toxicity.

PMID- 17216448
TI  - Fe(III)-enhanced Azo Reduction by Shewanella decolorationis S12.
AB  - Shewanella decolorationis S12 is capable of high rates of azo dye decolorization
      and dissimilatory Fe(III) reduction. Under anaerobic conditions, when Fe(III) and
      azo dye were copresent in S12 cultures, dissimilatory Fe(III) reduction and azo
      dye biodecolorization occurred simultaneously. Furthermore, the dye
      decolorization was enhanced by the presence of Fe(III). When 1 mM Fe(III) was
      added, the methyl red decolorizing efficiency was 72.1% after cultivation for 3
      h, whereas the decolorizing efficiency was only 60.5% in Fe(III)-free medium. The
      decolorizing efficiencies increased as the concentration of Fe(III) was increased
      from 0 to 6 mM. Enzyme activities, which mediate the dye decolorization and
      Fe(III) reduction, were not affected by preadaption of cells to Fe(III) and azo
      dye nor by the addition of chloramphenicol. Both the Fe(III) reductase and the
      azo reductase were membrane associated. The respiratory electron transport chain
      inhibitors metyrapone, dicumarol, and stigmatellin showed significantly different
      effects on Fe(III) reduction than on azo dye decolorization.

PMID- 17216449
TI  - Reactivation of aerobic and anaerobic ammonium oxidizers in OLAND biomass after
      long-term storage.
AB  - The biomass of an oxygen-limited autotrophic nitrification/denitrification
      (OLAND) biofilm reactor was preserved in various ways to find a storage method
      for both aerobic and anaerobic ammonium-oxidizing bacteria (AerAOB and AnAOB).
      Storage occurred at -20 degrees C with and without glycerol as cryoprotectant and
      at 4 and 20 degrees C with and without nitrate as redox buffer. After 2 and 5
      months, reactivation of AerAOB and AnAOB was achieved with the biomass stored at
      4 degrees C with and without nitrate and at 20 degrees C with nitrate. Moreover,
      the presence of the AerAOB and AnAOB was confirmed with fluorescent in situ
      hybridization (FISH). Preservation in a nitrate environment resulted in a lag
      phase for the AnAOB reactivation. The supplied nitrate was denitrified during
      storage, and a real-time polymerase chain reaction with nitrifying and
      denitrifying genes allowed to estimate that at least 1.0 to 6.0% of the OLAND
      biofilm consisted of denitrifiers. It was concluded that reactivation after long
      term storage is possible and that preservation at 4 degrees C without nitrate
      addition is the recommended storage technique. The possibility to store OLAND
      biomass will facilitate research on AnAOB and can overcome larger-scale start-up
      and inhibition problems of novel nitrogen processes involving AnAOB.

PMID- 17216450
TI  - Humic acid effect on pyrene degradation: finding an optimal range for pyrene
      solubility and mineralization enhancement.
AB  - The addition of humic acid (HA) to polycyclic aromatic hydrocarbon (PAH)
      contaminated systems has been shown to enhance, inhibit, or have no effect on the
      biodegradation of these PAHs. In this study, the surfactant effects of Elliott
      soil HA (ESHA) at two pH values were tested. At pH 7.0, ESHA did not behave as a
      surfactant. At pH 11.8, ESHA acted as a surfactant, as displayed by a decrease in
      surface tension with increasing concentrations of ESHA. The effect of ESHA on
      pyrene solubility was tested by adding 0 to 800 microg ESHA/g soil to soil
      slurries. Enhancement of pyrene apparent solubility demonstrated a dose- and time
      related effect. Broader doses from 0 to 10,080 microg ESHA/g soil and three
      higher doses from 3,360 to 10,080 microg ESHA/g soil were tested for their
      effects on pyrene mineralization by indigenous soil microorganisms and a novel
      PAH-degrading Mycobacterium sp. KMS in soil microcosms, respectively. ESHA
      amendments between 20 and 200 microg ESHA/g soil were found to consistently
      increase pyrene mineralization by indigenous microorganisms, while the 10,080
      microg ESHA/g soil produced inhibition and all other doses presented no effects.
      Pyrene degradation by M. KMS was significantly inhibited by the addition of the
      highest dose of ESHA.

PMID- 17216451
TI  - Amino acid supplementation reveals differential regulation of aflatoxin
      biosynthesis in Aspergillus flavus NRRL 3357 and Aspergillus parasiticus SRRC
      143.
AB  - Aflatoxins are toxic and carcinogenic secondary metabolites produced by the fungi
      Aspergillus flavus and Aspergillus parasiticus. To better understand the
      molecular mechanisms that regulate aflatoxin production, the biosynthesis of the
      toxin in A. flavus and A. parasticus grown in yeast extract sucrose media
      supplemented with 50 mM tryptophan (Trp) were examined. Aspergillus flavus grown
      in the presence of 50 mM tryptophan was found to have significantly reduced
      aflatoxin B(1) and B(2) biosynthesis, while A. parasiticus cultures had
      significantly increased B(1) and G(1) biosynthesis. Microarray analysis of RNA
      extracted from fungi grown under these conditions revealed 77 genes that are
      expressed significantly different between A. flavus and A. parasiticus, including
      the aflatoxin biosynthetic genes aflD (nor-1), aflE (norA), and aflO (omtB). It
      is clear that the regulatory mechanisms of aflatoxin biosynthesis in response to
      Trp in A. flavus and A. parasiticus are different. These candidate genes may
      serve as regulatory factors of aflatoxin biosynthesis.

PMID- 17216452
TI  - Production of L-Lysine from starch by Corynebacterium glutamicum displaying alpha
      amylase on its cell surface.
AB  - We engineered a Corynebacterium glutamicum strain displaying alpha-amylase from
      Streptococcus bovis 148 (AmyA) on its cell surface to produce amino acids
      directly from starch. We used PgsA from Bacillus subtilis as an anchor protein,
      and the N-terminus of alpha-amylase was fused to the PgsA. The genes of the
      fusion protein were integrated into the homoserine dehydrogenase gene locus on
      the chromosome by homologous recombination. L-Lysine fermentation was carried out
      using C. glutamicum displaying AmyA in the growth medium containing 50 g/l
      soluble starch as the sole carbon source. We performed L-lysine fermentation at
      various temperatures (30-40 degrees C) and pHs (6.0-7.0), as the optimal
      temperatures and pHs of AmyA and C. glutamicum differ significantly. The highest
      L-lysine yield was recorded at 30 degrees C and pH 7.0. The amount of soluble
      starch was reduced to 18.29 g/l, and 6.04 g/l L-lysine was produced in 24 h. The
      L-lysine yield obtained using soluble starch as the sole carbon source was higher
      than that using glucose as the sole carbon source after 24 h when the same amount
      of substrates was added. The results shown in the current study demonstrate that
      C. glutamicum displaying alpha-amylase has a potential to directly convert
      soluble starch to amino acids.

PMID- 17216453
TI  - Codon optimization of Bacillus licheniformis beta-1,3-1,4-glucanase gene and its
      expression in Pichia pastoris.
AB  - Beta-1,3-1,4-glucanase (EC3.2.1.73) as an important industrial enzyme has been
      widely used in the brewing and animal feed additive industry. To improve
      expression efficiency of recombinant beta-1,3-1,4-glucanase from Bacillus
      licheniformis EGW039(CGMCC 0635) in methylotrophic yeast Pichia pastoris GS115,
      the DNA sequence encoding beta-1,3-1,4-glucanase was designed and synthesized
      based on the codon bias of P. pastoris, the codons encoding 96 amino acids were
      optimized, in which a total of 102 nucleotides were changed, the G+C ratio was
      simultaneously increased from 43.6 to 45.5%. At shaking flask level, beta-1,3-1,4
      glucanase activity is 67.9 and 52.3 U ml(-1) with barley beta-glucan and lichenan
      as substrate, respectively. At laboratory fermentor level, the secreted protein
      concentration is approximately 250 mg l(-1). The beta-1,3-1,4-glucanase activity
      is 333.7 and 256.7 U ml(-1) with barley beta-glucan and lichenan as substrate,
      respectively; however, no activity of this enzyme on cellulose is observed.
      Compared to the nonoptimized control, expression level of the optimized beta-1,3
      1,4-glucanase based on preferred codons in P. pastoris shown a 10-fold higher
      level. The codon-optimized enzyme was approximately 53.8% of the total secreted
      protein. The optimal acidity and temperature of this recombinant enzyme were pH
      6.0 and 45 degrees C, respectively.

PMID- 17216454
TI  - Substrate and product hydrolysis specificity in family 11 glycoside hydrolases:
      an analysis of Penicillium funiculosum and Penicillium griseofulvum xylanases.
AB  - Two genes encoding family 11 endo-(1,4)-beta-xylanases from Penicillium
      griseofulvum (PgXynA) and Penicillium funiculosum (PfXynC) were heterologously
      expressed in Escherichia coli as glutathione S-transferase fusion proteins, and
      the recombinant enzymes were purified after affinity chromatography and
      proteolysis. PgXynA and PfXynC were identical to their native counterparts in
      terms of molecular mass, pI, N-terminal sequence, optimum pH, and enzymatic
      activity towards arabinoxylan. Further investigation of the rate and pattern of
      hydrolysis of PgXynA and PfXynC on wheat soluble arabinoxylan showed the
      predominant production of xylotriose and xylobiose as end products. The initial
      rate data from the hydrolysis of short xylo-oligosaccharides indicated that the
      catalytic efficiency increased with increasing chain length (n) of oligomer up to
      n = 6, suggesting that the specificity region of both Penicillium xylanases spans
      about six xylose units. In contrast to PfXynC, PgXynA was found insensitive to
      the wheat xylanase inhibitor protein XIP-I.

PMID- 17216456
TI  - Enhanced hydroxylation of imidacloprid by Stenotrophomonas maltophilia upon
      addition of sucrose.
AB  - Sucrose's ability to promote the hydroxylation of imidacloprid (IMI) by bacterium
      Stenotrophomonas maltophilia strain CGMCC 1.1788 was examined. Both growing
      culture and resting cells could transform IMI into 5-hydroxy IMI. Adding 2%
      sucrose to the growing culture transformation broth and 5% sucrose to the resting
      cell transformation broth resulted in biotransformation yields, respectively, 2.5
      and 9 times greater than without sucrose. In the growing culture transformation,
      sucrose increased biomass, which led to enhance hydroxylation of IMI. In the
      resting cell transformation, sucrose was used not as a carbon source but as an
      energy source for cofactor regeneration for hydroxylation of IMI. The
      hydroxylation activity of IMI was promoted eightfold by adding reduced
      nicotinamide adenine dinucleotide (NADH) to the cell-free extract. The
      hydroxylation of IMI was significantly inhibited by P450 inhibitor piperonyl
      butoxide. It seems that the hydroxylation of IMI by S. maltophilia CGMCC 1.1788
      might proceed through a system by cooperating with P450 enzyme.

PMID- 17216455
TI  - Thymidyl biosynthesis enzymes as antibiotic targets.
AB  - The two long-known "classical" enzymes of uridyl-5-methylation, thymidylate
      synthase and ribothymidyl synthase, have been joined by two alternative
      methylation enzymes, flavin-dependent thymidylate synthase and folate-dependent
      ribothymidyl synthase. These two newly discovered enzymes have much in common:
      both contain flavin cofactors, utilize methylenetetrahydrofolate as a source of
      methyl group, and perform thymidylate synthesis via chemical pathways distinct
      from those of their classic counterparts. Several severe human pathogens (e.g.,
      typhus, anthrax, tuberculosis, and more) depend on these "alternative" enzymes
      for reproduction. These and other distinctive properties make the alternative
      enzymes and their corresponding genes appealing targets for new antibiotics.

PMID- 17216457
TI  - A rare sugar xylitol. Part I: the biochemistry and biosynthesis of xylitol.
AB  - The rare sugar xylitol is a five-carbon polyol (pentitol) that has beneficial
      health effects. Xylitol has global markets and, therefore, it represents an
      alternative to current dominant sweeteners. The research on microbial reduction
      of D-xylose to xylitol has been focused on metabolically engineered
      Saccharomycess cerevisiae and Candida strains. The Candida strains have an
      advantage over the metabolically engineered S. cerevisiae in terms of D-xylose
      uptake and maintenance of the intracellular redox balance. Due to the current
      industrial scale production of xylitol, it has become an inexpensive starting
      material for the production of other rare sugar. The first part of this mini
      review concentrates on the biochemistry of xylitol biosynthesis and the problems
      related to intracellular redox balance.

PMID- 17216458
TI  - A rare sugar xylitol. Part II: biotechnological production and future
      applications of xylitol.
AB  - Xylitol is the first rare sugar that has global markets. It has beneficial health
      properties and represents an alternative to current conventional sweeteners.
      Industrially, xylitol is produced by chemical hydrogenation of D-xylose into
      xylitol. The biotechnological method of producing xylitol by metabolically
      engineered yeasts, Saccharomyces cerevisiae or Candida, has been studied as an
      alternative to the chemical method. Due to the industrial scale of production,
      xylitol serves as an inexpensive starting material for the production of other
      rare sugars. The second part of this mini-review on xylitol will look more
      closely at the biotechnological production and future applications of the rare
      sugar, xylitol.

PMID- 17216459
TI  - Complementary limiting factors of astaxanthin synthesis during photoautotrophic
      induction of Haematococcus pluvialis: C/N ratio and light intensity.
AB  - We investigated the effect of carbon/nitrogen (C/N) ratio on astaxanthin
      synthesis in Haematococcus pluvialis during photoautotrophic induction by
      continuous input of both CO(2)-air mixture and intense light. When H. pluvialis
      was induced by constant irradiance induction at 200 micromol photon m(-2) s(-1),
      there was a positive correlation with astaxanthin content and C/N ratio, which
      was similar to the case for heterotrophic induction. Lower C/N ratios did not
      retard Haematococcus encystment, but did increase culture biomass, resulting in a
      decrease in astaxanthin production because of light limitation. However,
      induction using variable irradiance showed that reduction of astaxanthin
      production at low C/N ratios was successfully overcome by simply increasing the
      light intensity from 200 to 300 micromol photon m(-2) s(-1) to overcome the light
      limitation. This resulted in a greatly enhanced astaxanthin synthesis in
      proportion to cell density in cultures with low C/N ratios. Our results indicate
      that light intensity is more critical than C/N ratio in astaxanthin production by
      H. pluvialis during photoautotrophic induction.

PMID- 17216460
TI  - Characterization of superoxide-stress sensing recombinant Escherichia coli
      constructed using promoters for genes zwf and fpr fused to lux operon.
AB  - To measure the toxicity experienced by superoxide-generating compounds, two
      plasmids were constructed in which the superoxide-inducible fpr and zwf promoters
      from Escherichia coli were fused to promoterless Vibrio fischeri luxCDABE operon
      present in plasmid pUCD615. The bioluminescent response of E. coli harboring
      these constructs was studied as a function of the toxicity and was shown to be
      specific for superoxide generating chemicals. The two promoters employed, fpr and
      zwf, responded differentially to the redox-chemicals tested. Furthermore, a
      DeltamarA strain bearing the fpr::luxCDABE fusion had a weaker response to
      paraquat (methyl viologen) than its isogenic parent strain, whereas zwf induction
      was not inhibited in DeltamarA or Deltarob strains. The fpr and zwf promoters
      were also induced by alkylating agents but were unresponsive in DeltamarA or
      Deltarob strains. Using optimized assay conditions, the abilities of these
      strains to differentially respond to superoxide stress and alkylating agents that
      may be present in contaminants proves them to be good biosensor candidates for
      monitoring toxicity.

PMID- 17216461
TI  - Bacillus methanolicus: a candidate for industrial production of amino acids from
      methanol at 50 degrees C.
AB  - Amino acids are among the major products in biotechnology in both volume and
      value, and the global market is growing. Microbial fermentation is the dominant
      method used for industrial production, and today the most important
      microorganisms used are Corynebacteria utilizing sugars. For low-prize bulk amino
      acids, the possibility of using alternative substrates such as methanol has
      gained considerable interest. In this mini review, we highlight the unique
      genetics and favorable physiological traits of thermotolerant methylotroph
      Bacillus methanolicus, which makes it an interesting candidate for overproduction
      of amino acids from methanol. B. methanolicus genes involved in methanol
      consumption are plasmid-encoded and this bacterium has a high methanol conversion
      rate. Wild-type strains can secrete 58 g/l of L: -glutamate in fed-batch cultures
      at 50 degrees C and classical mutants secreting 37 g/l of L: -lysine have been
      selected. The relative high growth temperature is an advantage with respect to
      both reactor cooling requirements and low contamination risks. Key genes in L: 
      lysine and L: -glutamate production have been cloned, high-cell density methanol
      fermentation technology established, and recently a gene delivery method was
      developed for this organism. We discuss how this new knowledge and technology may
      lead to the construction of improved L: -lysine and L: -glutamate producing
      strains by metabolic engineering.

PMID- 17216462
TI  - Alkane hydroxylases involved in microbial alkane degradation.
AB  - This review focuses on the role and distribution in the environment of alkane
      hydroxylases and their (potential) applications in bioremediation and
      biocatalysis. Alkane hydroxylases play an important role in the microbial
      degradation of oil, chlorinated hydrocarbons, fuel additives, and many other
      compounds. Environmental studies demonstrate the abundance of alkane degraders
      and have lead to the identification of many new species, including some that are
      (near)-obligate alkanotrophs. The availability of a growing collection of alkane
      hydroxylase gene sequences now allows estimations of the relative abundance of
      the different enzyme systems and the distribution of the host organisms.

PMID- 17216463
TI  - Production of tyrosine from sucrose or glucose achieved by rapid genetic changes
      to phenylalanine-producing Escherichia coli strains.
AB  - Escherichia coli K12 strains producing L-phenylalanine were converted to L
      tyrosine-producing strains using a novel genetic method for gene replacement. We
      deleted a region of the E. coli K12 chromosome including the pheA gene encoding
      chorismate mutase/prephenate dehydratase, its leader peptide (pheL), and its
      promoter using a new polymerase chain reaction-based method that does not leave a
      chromosomal scar. For high level expression of tyrA, encoding chorismate
      mutase/prephenate dehydrogenase, its native promoter was replaced with the strong
      trc promoter. The linked DeltapheLA and Ptrc-tyrA::Kan(R) genetic modifications
      were moved into L-phenylalanine producing strains by generalized transduction to
      convert L-phenylalanine-producing strains to L-tyrosine-producing strains.
      Moreover, introduction of a plasmid carrying genes responsible for sucrose
      degradation into these strains enabled L-tyrosine-production from sucrose.

PMID- 17216464
TI  - Contribution of the fermenting yeast strain to ethyl carbamate generation in
      stone fruit spirits.
AB  - Fermented fruit and beverages frequently contain ethyl carbamate (EC), a
      potentially carcinogenic compound that can be formed by the reaction of urea with
      ethanol. Both are produced by the yeast Saccharomyces cerevisiae with ethanol as
      the major end product of hexose fermentation and urea as a by-product in arginine
      catabolism. In spirit production, EC can also be derived from cyanide introduced
      by stone fruit. To determine the relative contribution of yeast metabolism to EC
      production, we genetically engineered a diploid laboratory strain to reduce the
      arginase activity, thus blocking the pathway to urea production. For this
      purpose, strains with either a heterozygous CAR1/car1 deletion or a homozygous
      defect (car1/car1) were constructed. These strains were compared to the parental
      wild type and to an industrial yeast strain in cherry mash fermentations and
      spirit production. The strain with the homozygous car1 deletion showed a
      significant reduction of EC in the final spirits in comparison to the non
      engineered controls. Nevertheless, using this strain for fermentation of
      stoneless cherry mashes did not completely impede EC formation. This indicates
      another, as yet unidentified, source for this compound.

PMID- 17216465
TI  - High-temperature biotrickling filtration of hydrogen sulphide.
AB  - Biofiltration of malodorous reduced sulphur compounds such as hydrogen sulphide
      has been confined to emissions that are at temperatures below 40 degrees C
      despite the fact that there are many industrial emissions (e.g. in the pulp and
      paper industry) at temperatures well above 40 degrees C. This paper describes our
      study on the successful treatment of hydrogen sulphide gas at temperatures of 40,
      50, 60 and 70 degrees C using a microbial community obtained from a hot spring.
      Three biotrickling filter (BTF) systems were set up in parallel for a continuous
      run of 9 months to operate at three different temperatures, one of which was
      always at 40 degrees C as a mesophilic control and the other two were for
      exploring high-temperature operation up to 70 degrees C. The continuous
      experiment and a series of batch experiments in glass bottles (250 ml) showed
      that addition of glucose and monosodium glutamate enhanced thermophilic
      biofiltration of hydrogen sulphide gas and a removal rate of 40 g m(-3) h(-1) was
      achieved at 70 degrees C. We suggest that the glucose is acting as a carbon
      source for the existing microbial community in the BTFs, whereas glutamate is
      acting as a compatible solute. The use of such organic compounds to enhance
      biodegradation of hydrogen sulphide, particularly at high temperatures, has not
      been demonstrated to our knowledge and, hence, has opened up a range of
      possibilities for applying biofiltration to hot gas effluent.

PMID- 17216466
TI  - Fusion of the genes for AHL-lactonase and S-layer protein in Bacillus
      thuringiensis increases its ability to inhibit soft rot caused by Erwinia
      carotovora.
AB  - Two genes, ctc and ctc2, responsible for surface layer (S-layer) protein
      synthesis in Bacillus thuringiensis CTC, were mutated and resulted in B.
      thuringiensis Tr5. To synthesize and express the N-acyl-homoserine lactonase (AHL
      lactonase) in the extracellular space of B. thuringiensis, the aiiA ( 4Q7 ) gene
      (an AHL-lactonase gene from B. thuringiensis 4Q7), which confers the ability to
      inhibit plant soft rot disease in B. thuringiensis 4Q7, was fused with the
      upstream sequence of the ctc gene, which in turn is essential for S-layer protein
      secretion and anchoring on the cell surface. The resulting fusion gene, slh-aiiA,
      was expressed in B. thuringiensis Tr5 to avoid competition for the extracellular
      space with the native S-layer protein. Our results indicate that B. thuringiensis
      Tr5 containing the fusion gene slh-aiiA displayed high extracellular AHL
      degrading activity. When compared with wild-type B. thuringiensis strains, the
      ability of the constructed strain to inhibit soft rot disease caused by Erwinia
      carotovora SCG1 was markedly increased. These findings provide evidence for a
      significant advance in our ability to inhibit soft rot disease caused by E.
      carotovora.

PMID- 17216467
TI  - Growth and laccase production kinetics of Trametes versicolor in a stirred tank
      reactor.
AB  - White rot fungi are a promising option to treat recalcitrant organic molecules,
      such as lignin, polycyclic aromatic hydrocarbons, and textile dyes, because of
      the lignin-modifying enzymes (LMEs) they secrete. Because knowledge of the
      kinetic parameters is important to better design and operate bioreactors to
      cultivate these fungi for degradation and/or to produce LME(s), these parameters
      were determined using Trametes versicolor ATCC 20869 (ATCC, American Type Culture
      Collection) in a magnetic stir bar reactor. A complete set of kinetic data has
      not been previously published for this culture. Higher than previously reported
      growth rates with high laccase production of up to 1,385 U l(-1) occurred during
      growth without [Formula: see text] or glucose limitation. The maximum specific
      growth rate averaged 0.94 +/- 0.23 day(-1), whereas the maximum specific
      substrate consumption rates for glucose and ammonium were 3.37 +/- 1.16 and 0.15
      +/- 0.04 day(-1), respectively. The maximum specific oxygen consumption rate was
      1.63 +/- 0.36 day(-1).

PMID- 17216468
TI  - Bioconversion of butyronitrile to butyramide using whole cells of Rhodococcus
      rhodochrous PA-34.
AB  - Butyramide is an important chemical commodity, which is used for the synthesis of
      hydroxamic acids and electrorheological fluids and for the preparation of beta
      amodoorganotin compounds. The nitrile hydratase (Nhase) of Rhodococcus
      rhodochrous PA-34 catalyzed the conversion of butyronitrile to butyramide. The
      maximum Nhase activity [18 U/mg dry cell weight (dcw)] of whole cells of R.
      rhodochrous PA-34 was observed at pH 7.0 with 10% (v/v) butyronitrile and 1 mg
      cells (dcw)/ml reaction mixture at 10 degrees C. The cells of R. rhodochrous PA
      34 retained almost 50% activity when incubated for 1 h in the presence of 85%
      (v/v) butyronitrile. A yield of 597 g of butyramide (6.8 M) was obtained using
      60% (v/v) butyronitrile, 1 g cells (dry weight) in a 1-l batch reaction at 10
      degrees C for 6 h.

PMID- 17216469
TI  - Is PET-CT the only option?

PMID- 17216470
TI  - Highlights of the European Association of Nuclear Medicine Congress, Athens,
      Greece, 30 September to 4 October 2006.
AB  - The 2006 EANM Congress, held in Athens, Greece, was once again a major event in
      the nuclear medicine scientific and educational calendar. The scientific
      programme, which included the second biennial ISRTRD meeting, confirmed the major
      developments taking place in (1) the diagnostic and prognostic uses of nuclear
      medicine imaging (both in PET and in single-photon studies), (2) radionuclide
      therapies, (3) radiochemistry and radiopharmacy, and (4) physics. This paper
      outlines the major findings in each of these areas.

PMID- 17216471
TI  - Early detection and monitoring of cartilage alteration in the experimental
      meniscectomised guinea pig model of osteoarthritis by 99mTc-NTP 15-5
      scintigraphy.
AB  - PURPOSE: This study in the meniscectomised guinea pig aimed to demonstrate that
      the radiotracer (99m)Tc-NTP 15-5 would have pathophysiological validity for in
      vivo osteoarthritis imaging. METHODS: The specificity of (99m)Tc-NTP 15-5 for
      cartilage was determined in healthy animals (n = 13), by tissue radioactivity
      counting, joint autoradiography and scintigraphy. (99m)Tc-NTP 15-5 scintigraphy
      was performed at 20, 50, 80, 115, 130, 150 and 180 days after medial meniscectomy
      (n = 10 MNX) or sham operation (n = 5), and scintigraphic ratios
      (operated/contralateral) were calculated for femoral (F) and tibial (T) areas. F
      and T ratios were compared with those of (99m)Tc-MDP bone scintigraphy. At the
      study end-point, autoradiographic analysis of joint (99m)Tc-NTP 15-5 distribution
      and macroscopic scoring of cartilage integrity were performed. RESULTS: The high
      and specific accumulation of (99m)Tc-NTP 15-5 in normal cartilage (about 5.5 +/-
      1.7 % of injected dose/g of tissue), which permitted joint imaging with high
      contrast, was affected by osteoarthritis. In the MNX group, (99m)Tc-NTP 15-5
      accumulation in cartilage within the operated joint, relative to the
      contralateral joint, was observed to change in the same animals as pathology
      progressed. Although F and T ratios were significantly higher in MNX (F = 1.7 +/-
      0.2; T = 1.6 +/- 0.1) than in shams (F = 1.0 +/- 0.1; T = 1.0 +/- 0.1) at day 50,
      they were significantly lower in MNX (F = 0.6 +/- 0.1; T = 0.7 +/- 0.1) than in
      shams (F = 1.0 +/- 0.1; T = 0.9 +/- 0.1) at day 180. No change in (99m)Tc-MDP
      uptake was observed over 6 months. Macroscopic analysis confirmed features of
      osteoarthritis only in MNX knees. CONCLUSION: These results in MNX guinea pigs
      provide additional support for the use of (99m)Tc-NTP 15-5 for in vivo imaging of
      osteoarthritis.

PMID- 17216473
TI  - Rituximab plus ASHAP for the treatment of patients with relapsed or refractory
      aggressive non-Hodgkin's lymphoma: a single-centre study of 20 patients.
AB  - The anti-CD20 antibody rituximab improves the results of first-line therapy in
      aggressive non-Hodgkin's lymphoma (NHL) of B cell lineage. The purpose of this
      retrospective study was to evaluate its efficacy and toxicity in combination with
      the doxorubicine, methylprednisolone, high-dose cytarabine, cisplatin (ASHAP)
      protocol, an established treatment regimen for relapsed or refractory aggressive
      NHL. After a median of four cycles, 9 of 20 patients treated achieved a complete
      remission and 6 a partial remission, resulting in a total response rate of 75%.
      Remissions were not only seen in patients with relapsed lymphomas but also in
      patients with primary refractory or transformed indolent lymphomas. The outcome
      in cases with an international prognostic index score > or =2 was poor. Five of
      15 responders received consolidating high-dose therapy with autologous stem cell
      transplantation. All of them are in ongoing remission. The main toxicity was
      myelosuppression, with neutropenias or thrombocytopenias of World Health
      Organization (WHO) grades III or IV developing in more than 90% of the cycles.
      There was one therapy-related death due to neutropenic sepsis. Non-hematologic
      toxicity was generally mild. At the time of analysis, six patients have died.
      After a median observation time of 17.5 months, the 2-year overall survival rate
      is 62%. ASHAP plus rituximab is an active and well-tolerated salvage protocol for
      patients with relapsed or refractory aggressive NHL, which compares favourably
      with other immuno-chemotherapy regimens, especially in patients with primary
      refractory or transformed indolent lymphomas.

PMID- 17216474
TI  - Necrobiotic xanthogranuloma successfully treated with autologous stem cell
      transplantation.
AB  - Paraproteinemia can be complicated by necrobiotic xanthogranuloma. Therapeutic
      options for this progressive disease are limited, and there is no agreement on a
      single best strategy. We report the case of a patient with a massive periorbital
      infiltration narrowing the palpebral fissure and blinding the patient.
      Conventional myeloma therapy had only limited benefit in our patient. However, he
      was successfully treated with high-dose chemotherapy followed by autologous stem
      cell transplantation, rendering the patient free of symptoms. This is the first
      report of autologous stem cell transplantation in a patient with necrobiotic
      xanthogranuloma.

PMID- 17216472
TI  - 99mTc-Annexin A5 for noninvasive characterization of atherosclerotic lesions:
      imaging and histological studies in myocardial infarction-prone Watanabe
      heritable hyperlipidemic rabbits.
AB  - PURPOSE: Apoptosis is commonly observed in advanced atherosclerotic lesions.
      99mTc-annexin A5 (99mTc-annexin V) has been proposed as a potential tracer for
      imaging apoptosis in atherosclerotic plaques. Accordingly, we determined the
      usefulness of 99mTc-annexin A5 as an atherosclerosis imaging tracer in a rabbit
      model (myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits;
      WHHLMI rabbits) of spontaneous atherosclerosis. METHODS: The WHHLMI and control
      rabbits were injected intravenously with 99mTc-annexin A5. After in vivo planar
      imaging, the radioactivity in the aorta was measured. Autoradiography, TUNEL
      staining, Azan-Mallory staining and immunohistological studies were performed
      serially throughout the aorta. RESULTS: 99mTc-Annexin A5 accumulation in the
      aorta of the WHHLMI rabbits was 5.6-fold higher than in that of control rabbits.
      Autoradiography showed heterogeneous multifocal accumulation of 99mTc-annexin A5
      in WHHLMI rabbits. 99mTc-Annexin A5 accumulation was highest in the atheromatous
      lesions (6.2+/-2.5, %IDxBW/mm2x10(3)), followed in decreasing order by neointimal
      (4.9+/-1.3), fibroatheromatous (4.5+/-1.9), and collagen-rich lesions (3.3+/
      1.4). The regional 99mTc-annexin A5 accumulation was significantly correlated
      with the TUNEL-positive cell density, macrophage density and "vulnerability
      index," an index of the morphological destabilized characteristics. The in vivo
      imaging clearly visualized the atherosclerotic lesions in WHHLMI rabbits.
      CONCLUSION: The present study in WHHLMI rabbits showed higher 99mTc-annexin A5
      accumulation in grade IV atheroma than in other more stable lesions. 99mTc
      Annexin A5 may be useful in identifying atheroma that is at higher risk for
      rupture and possibly in assessing the response to anti-atherosclerotic therapy.

PMID- 17216475
TI  - Sex-structured HIV/AIDS model to analyse the effects of condom use with
      application to Zimbabwe.
AB  - We present a sex-structured model for heterosexual transmission of HIV/AIDS in a
      community. The model is formulated using integro-differential equations, which
      are shown to be equivalent to delay differential equations with a time delay due
      to incubation period. The sex-structured HIV/AIDS model divides the population
      into a two sex-structure consisting of females and males. The threshold and
      equilibria for the model are determined and stabilities are examined. We extend
      the model to focus on the effects of condom use as a single-strategy approach in
      HIV prevention in the absence of any treatment. Initially we model the use of
      male condoms and further extend the model to incorporate the use of both female
      and male condoms. The model includes two primary factors in condom use to control
      HIV that are condom efficacy and compliance. The exposure risk of infection after
      each intervention is obtained. Basic reproductive numbers for these models are
      computed and compared to assess the effectiveness of male and female condom use
      in a community. The models are numerically analysed to assess the effectiveness
      of condom use on the transmission dynamics of HIV/AIDS using demographic and
      epidemiological parameters for Zimbabwe. The study demonstrates the use of sex
      structured HIV/AIDS models in assessing the effectiveness of female and male
      condom use as a preventative strategy in a heterosexually active population.

PMID- 17216476
TI  - Factors affecting drug treatment compliance in patients with rheumatoid
      arthritis.
AB  - We prospectively examined 100 rheumatoid arthritis (RA) patients to calculate
      drug compliance rates, characteristics of compliant and non-compliant patients,
      and changes in compliance over time. Three assessments were obtained over a one
      year follow-up. Detailed drug history of RA and for concomitant disease was
      queried. Sedimentation rate, C-reactive protein, and rheumatoid factor values,
      Ritchie articular index, morning stiffness, and health assessment questionnaire
      were evaluated. Twenty-six patients (30.2%) were consistently compliant and 10
      patients (11.6%) were consistently non-compliant. Older age was associated with a
      greater likelihood of compliance. Comparison of compliant and non-compliant
      groups revealed no statistically significant difference in distribution of
      gender, disease duration, and total number of pills taken for RA and/or total
      number of pills taken for any reason. In conclusion, compliance to drugs in RA
      patients is a common problem. Clinical and laboratory activity of RA had less
      influence on drug compliance. Older age is associated with a greater likelihood
      of compliance.

PMID- 17216478
TI  - "Silent" bone stress injuries in the feet of diabetic patients with
      polyneuropathy: a report on 12 cases.
AB  - BACKGROUND: Bone stress injuries are rarely being diagnosed in patients with
      sensory neuropathy, most likely because they may be silent in terms of pain. Load
      related pain is considered a key feature of any bone stress injury, a symptom,
      which may be partially or completely absent in subjects with sensory neuropathy
      (loss of protective sensation). We evaluated the clinical course of bone stress
      injuries in insensitive feet in diabetic patients with polyneuropathy. METHODS:
      We investigated 12 consecutive diabetic patients with bone stress injuries of the
      foot (bone marrow edema, bone bruise and microtrabecular fractures, on magnetic
      resonance imaging MRI), which were undetectable on plain X-ray. All patients
      suffered from diabetic polyneuropathy, none of them had an active foot ulcer.
      RESULTS: The patients presented with a swollen foot, which was only mildly
      painful and did not prevent them from walking. Complaints were related to the
      swelling, which increased during load-bearing. In seven cases, a traumatic event
      preceding the onset of symptoms could be ascertained. MRI disclosed stress
      injuries in 2.5 (1-8) [median (range)] bones per foot. In 11 patients, treatment
      was started immediately by off-loading with total contact cast for 17 (8-52)
      weeks, followed by gradual increase in weight bearing. One patient unfortunately
      received off-loading treatment only after deforming fractures had developed. All
      bone injuries healed uneventuelly in eight patients, and with residual mild
      osteoarthrosis in three patients without gross deformities. However, the
      untreated patient developed severe Charcot foot deformity. CONCLUSIONS: In
      diabetic patients with polyneuropathy, symptoms of bone stress injuries of the
      foot are atypical, in that there is load-related swelling rather than load
      related pain. Immediate diagnosis, and treatment with off-loading, leads to a
      restitutio ad integrum like in non-neuropathic patients. Delayed cessation of
      overuse, however, may cause irreversible joint and bone damage (Charcot foot).

PMID- 17216477
TI  - Superiority of a combined treatment of Alendronate and Alfacalcidol compared to
      the combination of Alendronate and plain vitamin D or Alfacalcidol alone in
      established postmenopausal or male osteoporosis (AAC-Trial).
AB  - A combined therapy with the strongly antiresorptive Alendronate and the
      pleiotropically acting D-hormone analogue Alfacalcidol may have additive effects
      on bone quality, falls and fracture risk in established osteoporosis. The aim of
      this study (Alfacalcidol Alendronate Combined-AAC) was to compare the efficacy
      and safety of a combined parallel therapy with Alendronate and Alfacalcidol to
      the treatment with either Alendronate in combination with plain vitamin D or
      Alfacalcidol alone in patients with established postmenopausal or male
      osteoporosis. Ninety patients were included as matched triplets to receive
      randomly either 1 microg Alfacalcidol daily + 500 mg calcium (group A, n = 30) or
      70 mg Alendronate weekly + 1,000 mg calcium + 1,000 IU vitamin D daily (group B,
      n = 30) or 1 microg Alfacalcidol daily + 70 mg Alendronate weekly + 500 mg
      calcium daily (group C, n = 30). Patients were recruited in one centre and were
      followed up for 24 months. Analysis was intention-to-treat and the primary
      outcome was lumbar spine and total hip bone mineral density (measured observer
      blind). BMD was measured at the lumbar spine and at the proximal femur with dual
      energy X-ray absorptiometry (LUNAR Prodigy, GE, USA) at the beginning and after
      12 and 24 months. During the 2-year-study we observed descriptively significant
      increases at the lumbar spine of 3.0% in group A compared to baseline, of 5.4% in
      group B and of 9.6% in group C, respectively. The superiority of the Alendronate
      + Alfacalcidol treatment group over Alfacalcidol alone and over Alendronate +
      vitamin D was of more than large rele-vance (both tests: MW > 0.71; CI-LB > 0.64;
      P < 0.001). We also observed median increases of the BMD at the total hip of 1.5%
      in group A, of 2.4% in group B and of 3.8% in group C, respectively. The
      superiority of group C over group A and over group B again was relevant and
      statistically significant in a descriptive sense. After 2 years there was a
      tendency towards higher rates of vertebral and non-vertebral fractures in group A
      and B as compared to C. Taking both fracture types together we observed 9, 10 and
      2 "osteoporotic fractures" in groups A, B and C, respectively. The comparison of
      group C with pooled groups A and B and with each single group gave a relevantly
      lower fracture rate for the combination of Alendronate and Alfacalcidol.
      Furthermore a lower rate of falls was observed for the combination Alendronate
      plus Alfacalcidol versus Alendronate + vitamin D, but not versus Alfacalcidol
      alone. We found 80% of the patients in the Alendronate + Alfacalcidol group free
      from back pain at month 24, compared to 30% in the Alendronate + vitamin D and
      43% in the Alfacalcidol monotherapy group. The superiority is relevant (both
      tests: MW > 0.64; CI-LB > 0.56; P < 0.003). Pain decrease also occurred more
      rapidly in the Alendronate + Alfacalcidol group than in the other groups. In
      general side effects in all groups were mild, and only four cases of moderate
      hypercalcuria in group A and one in group C were reported, but no case of
      hypercalcemia was documented. In conclusion, the combination therapy with
      Alendronate and Alfacalcidol exhibited superiority in terms of BMD, overall
      fractures, rate of falls and back pain over either Alendronate in combination
      with plain vitamin D or Alfacalcidol alone. The overall safety profiles of the
      three treatment regimens were found to be not different in this study.

PMID- 17216479
TI  - Over-expression of rice OsAGO7 gene induces upward curling of the leaf blade that
      enhanced erect-leaf habit.
AB  - High-yield cultivars are characterized by erect leaf canopies that optimize
      photosynthesis and thus favor increased biomass. Upward curling of the leaf blade
      (called rolled leaf) can result in enhanced erect-leaf habit, increase erect
      duration and promote an overall erect leaf canopy. The rice mutant R05, induced
      through transferred DNA (T-DNA) insertion, had the rolled-leaf trait. The leaves
      in the wild type demonstrated natural drooping tendencies, resulting in
      decreasing leaf erection indices (LEIs) during senescence at the 20th day after
      flowering. Conversely, LEIs of the leaves in R05 remained high, even 20-day post
      flowering. We applied T-DNA tagging and isolated a rolled-leaf gene from rice
      which, when over-expressed, could induce upward curling of the leaf blade. This
      gene encodes for a protein of 1,048 amino acids including the PAZ and PIWI
      conserved domains, belonging to the Argonaute (AGO) family. There are at least 18
      members of the AGO family in rice. According to high-sequence conservation, the
      rolled-leaf gene in rice could be orthologous to the Arabidopsis ZIP/Ago7 gene,
      so we called it OsAGO7. These results provide a possible opportunity for
      implementing OsAGO7 gene in crop improvement.

PMID- 17216480
TI  - Ectopic expression of Dahlia merckii defensin DmAMP1 improves papaya resistance
      to Phytophthora palmivora by reducing pathogen vigor.
AB  - Phytophthora spp., some of the more important casual agents of plant diseases,
      are responsible for heavy economic losses worldwide. Plant defensins have been
      introduced as transgenes into a range of species to increase host resistance to
      pathogens to which they were originally susceptible. However, the effectiveness
      and mechanism of interaction of the defensins with Phytophthora spp. have not
      been clearly characterized in planta. In this study, we expressed the Dahlia
      merckii defensin, DmAMP1, in papaya (Carica papaya L.), a plant highly
      susceptible to a root, stem, and fruit rot disease caused by Phytophthora
      palmivora. Extracts of total leaf proteins from transformed plants inhibited
      growth of Phytophthora in vitro and discs cut from the leaves of transformed
      plants inhibited growth of Phytophthora in a bioassay. Results from our
      greenhouse inoculation experiments demonstrate that expressing the DmAMP1 gene in
      papaya plants increased resistance against P. palmivora and that this increased
      resistance was associated with reduced hyphae growth of P. palmivora at the
      infection sites. The inhibitory effects of DmAMP1 expression in papaya suggest
      this approach has good potential to impart transgenic resistance against
      Phytophthora in papaya.

PMID- 17216481
TI  - The floral volatile, methyl benzoate, from snapdragon (Antirrhinum majus)
      triggers phytotoxic effects in Arabidopsis thaliana.
AB  - Previously it has been shown that the floral scent of snapdragon flowers consists
      of a relatively simple mixture of volatile organic compounds (VOCs). These
      compounds are thought to be involved in the attraction of pollinators; however,
      little is known about their effect on other organisms, such as neighboring
      plants. Here, we report that VOCs from snapdragon flowers inhibit Arabidopsis
      root growth. Out of the three major snapdragon floral volatiles, myrcene, (E)
      beta-ocimene, and methyl benzoate (MB), MB was found to be primarily responsible
      for the inhibition of root growth. Ten micromoles MB reduced root length by
      72.6%. We employed a microarray approach to identify the MB target genes in
      Arabidopsis that were responsible for the root growth inhibition phenotype in
      response to MB. These analyses showed that MB treatment affected 1.33% of global
      gene expression, including cytokinin, auxin and other plant-hormone-related
      genes, and genes related to seed germination processes in Arabidopsis.
      Accordingly, the root growth of cytokinin (cre1) and auxin (axr1) response
      mutants was less affected than that of the wild type by the volatile compound:
      roots of the treated mutants were reduced by 45.1 and 56.2%, respectively,
      relative to untreated control mutants.

PMID- 17216482
TI  - Regulation of gibberellin 20-oxidase1 expression in spinach by photoperiod.
AB  - The multifunctional gibberellin (GA) 20-oxidase [GA(53), 2-oxoglutarate:oxygen
      oxidoreductase (20-oxidizing), EC 1.14.11] has been extensively investigated in
      various species at the genetic and molecular levels, but not at the protein
      level. Here, we report on expression of GA20ox1 protein in spinach (Spinacia
      oleracea L.) in response to photoperiod. Polyclonal antibodies were raised
      against recombinant SoGA20ox1 in a chicken. These antibodies immuno-inhibited the
      enzymatic activity of the recombinant SoGA20ox1 and immuno-precipitated SoGA20ox1
      (43 kDa) isolated from spinach shoot tips. Northern and western analyses showed
      that the levels of SoGA20ox1 transcript and protein increased in the blades,
      petioles, young leaves, and tips in response to long-day (LD) conditions. The
      transcript and protein levels of the SoGA20ox1 gene were up-regulated in the
      petioles and tips in a time-dependent manner. The estimated number of SoGA20ox1
      protein molecules per cell was approximately 13-fold higher in tips grown in LD
      than in short-day (SD) conditions. The levels of SoGA20ox1 protein gradually
      decreased in tips when spinach plants grown in LD were transferred to SD
      conditions. SoGA20ox1 transcripts were detected by in situ hybridization in
      rapidly growing tissues--such as the shoot apical meristem, leaf and flower
      primordia, leaflets, and vascular tissues--but not in the expanding subapical
      region. In petioles, expression of SoGA20ox1 was detected in the companion cells.

PMID- 17216483
TI  - Arabidopsis thaliana GH3.9 influences primary root growth.
AB  - Auxins regulate a complex signal transduction network to direct plant
      development. Auxin-responsive genes fit into three major classes: the so-called
      auxin/indole-3-acetic acid (Aux/IAA), the GH3, and the small auxin-up RNA (SAUR)
      gene families. The 20-member Arabidopsis thaliana GH3 gene family has been
      subdivided into three groups. In vitro studies have shown that most Group II
      members function as IAA-amido synthetases to conjugate amino acids to the plant
      hormone auxin. Here we report the role of a previously uncharacterized GH3 gene
      family member, GH3.9, in root growth. Unlike most other Group II family members,
      GH3.9 expression was repressed by low concentrations of exogenous IAA in
      seedlings. Transgenic plants harboring a GH3.9 promoter::reporter gene construct
      indicate that GH3.9 is expressed in the root-hypocotyl junction, leaves and the
      shoot apical meristem of young seedlings, in mature embryos, and in the root
      vascular tissue. Expression was also observed in lateral root tips when seedlings
      were treated with exogenous IAA. Inverse PCR was used to identify an activation
      tagged T-DNA insertion in chromosome 2 near the 5'UTR region of At2g47750
      (GH3.9). Plants homozygous for the T-DNA insertion (gh3.9-1 mutants) had reduced
      GH3.9 expression, no obvious effects on apical dominance or leaf morphology,
      greater primary root length, and increased sensitivity to indole-3-acetic acid
      (IAA)-mediated root growth inhibition. Additional T-DNA insertion alleles and
      transgenic plants with reduced GH3.9 transcript levels due to RNA-interference
      (RNAi) also showed these same phenotypes. Our results provide new information on
      the function of GH3.9 in roots where it is likely to control auxin activity
      through amino acid conjugation.

PMID- 17216484
TI  - Epidemiological study on Clonorchis sinensis infection in Shenzhen area of
      Zhujiang delta in China.
AB  - To study the transmission route and epidemiological features of Clonorchis
      sinensis infection in Shenzhen area, which is the biggest immigration city in the
      south of China, we examined 1,473 individuals (710 males and 763 females) to
      assess the current status of C. sinensis infection among the people in a village
      of Shenzhen in Zhujiang delta of Guangdong province, China. Freshwater snails,
      630, of different species known as the first intermediate host of C. sinensis
      were collected and examined for cercaria infection, and 430 freshwater fishes of
      different species as the second intermediate host were examined for metacercaria
      infection. Among 1,473 people examined, 70 (4.75%) were found infected with C.
      sinensis. By counting eggs per gram feces (EPG), it was found that the intensity
      of infection in males was stronger than that of females, and the average EPG was
      41.87 in all population. Snails, 1.15%, were infected with cercariae of C.
      sinensis. The average infection rate of freshwater fishes of 15 species with
      metacercariae of C. sinensis was 16.97%, and the carps reached the highest
      infection rate (40.74%). A questionnaire was designed with 12 questions covering
      socioeconomic conditions and human behavior, contamination of the environment,
      and fishponds. Of 1,473 interviewees, 54% did not know about fluke disease or its
      transmission route, 12% of those who knew about the fluke believed that the
      infection causes no harm or only slight harm to their health. Of the
      interviewees, 27%, ate raw fish at least one to two times per month. Of families,
      5% used the same utensils for both raw fish and cooked food. Of the fishpond
      owners, 40% fed their fishes with feces of domestic animals and humans. All these
      factors of unhealthy behaviors, poor knowledge, inappropriate farming/fishery
      practices, and eating raw fish have made the prevalence of clonorchiasis increase
      in humans in the Shenzhen area. It is urgent to perform a control program,
      including health education, environmental modification, reform of traditional
      farming/fishery practice, mass screening, and chemotherapy for humans, and the
      management of domestic animals to decrease C. sinensis infection in the human
      population in Shenzhen.

PMID- 17216485
TI  - Evidence for multiple mitochondrial lineages of Fasciola hepatica (liver fluke)
      within infrapopulations from cattle and sheep.
AB  - The economic, veterinary, and medical impact of the parasite Fasciola hepatica,
      liver fluke, is difficult to alleviate due to increasing incidences of resistance
      to the principal anthelmintic drugs. These have occurred in widely separated
      regions. The rate of response to selection imposed by such drugs will be
      dependent on the genetic variation present in the F. hepatica gene pool, but this
      is at present unknown. We have assessed the genetic diversity of mitochondrial
      haplotypes found in the infrapopulation of flukes recovered from a calf of known
      provenance and from six other cattle and sheep hosts located in Ireland and four
      from elsewhere. Our results revealed that at least ten different mitochondrial
      composite PCR-restriction fragment length polymorphism haplotypes had been
      acquired by a single animal in 1 year, and there was comparable diversity in six
      other definitive hosts carrying field-acquired infections. The extent of
      divergence between these fluke lineages suggests that they predate the last ice
      age and, thus, cannot have developed in Northern Europe. A consequence of this
      high level of diversity is that there will be frequent selection for anthelmintic
      resistance and rapid responses to climatic changes.

PMID- 17216486
TI  - Morphology and reproductive mode of Blastocystis hominis in diarrhea and in
      vitro.
AB  - The in vitro culture of Blastocystis hominis in Roswell Park Memorial Institute
      (RPMI) 1,640 medium containing 20% calf serum is described. The morphological and
      reproductive mode studies of B. hominis in symptomatic patients' faeces and in
      further RPMI 1,640 medium-cultured samples were undertaken by light microscopy
      using iodine staining and hematoxylin staining. Three distinct morphological
      forms, vacuolar, granular and amoeboid, were distinguished in faeces and in vitro
      cultures. The cystic form was detected in long-term cultures. Five modes of
      reproduction, namely, binary fission, endodyogeny, plasmotomy, budding and
      schizogeny were observed.

PMID- 17216487
TI  - Genetic diversity in the trypanorhynch cestode Tentacularia coryphaenae Bosc,
      1797: evidence for a cosmopolitan distribution and low host specificity in the
      teleost intermediate host.
AB  - Partial large subunit (28S) rRNA gene (LSU) sequences were studied from
      Tentacularia coryphaenae (Cestoda: Trypanorhyncha) plerocercoids from the
      southern Java coast, Indonesia, collected from two different localities and five
      different host species. The teleost hosts belonged to four fish families with an
      overlapping depth range of 0-885 m. The LSU sequences were identical,
      demonstrating that all specimens belonged to the same species. They also
      corresponded to a sequence of T. coryphaenae from the Blue shark Prionace glauca
      in the North Atlantic, giving genetic evidence for the cosmopolitan distribution
      of the species. A 1,851 bp region of mitochondrial (mt) DNA (coding for partial
      cytochrome c oxidase subunit I (cox1), complete trnT and partial 16S ribosomal
      RNA) showed a very low level of intra-specific variation of 1%. Pairwise
      comparisons of published sequences for partial LSU rDNA and the same region of
      mtDNA demonstrated that the same regions varied by 8% in the mtDNA for two
      genotypes (G1 and G4) of Echinococcus granulosus (order Cyclophyllidea), at 16%
      in newly sequenced Kotorella pronosoma from the same trypanorhynch family and at
      23% in Grillotia pristiophori from a different superfamily. The high genetic
      homogeneity in T. coryphaenae is explained by a constant gene flow between
      different regions and hosts along the Indonesian coast caused by extensive
      migrations of the second intermediate/paratenic and also the final hosts.
      Implications for the zoogeographical distribution, host specificity of the
      species and future research are discussed.

PMID- 17216488
TI  - Comparative evaluation of the sensitivity of LAMP, PCR and in vitro culture
      methods for the diagnosis of equine piroplasmosis.
AB  - The sensitivity of LAMP, PCR and in vitro culture methods for the detection of
      Theileria equi and Babesia caballi was evaluated using tenfold serially diluted
      culture parasites. On day 1 post-culture, both T. equi and B. caballi parasites
      could only be observed at 1% parasite dilution from the in vitro culture method,
      whereas LAMP could detect up to 1 x 10(-3)% of both T. equi and B. caballi
      parasite dilutions, whilst PCR could detect 1 x 10(-3)% T. equi and 1 x 10(-1)%
      B. caballi parasite dilutions. On day 7 post-culture, the detection limit for T.
      equi and B. caballi in the in vitro culture increased up to 1 x 10(-6)%, whereas
      LAMP detection limit increased to 1 x 10(-10)% for both parasites, whilst the PCR
      detection limit increased to 1 x 10(-10)% and 1 x 10(-6)% for T. equi and B.
      caballi, respectively. Furthermore, LAMP and PCR amplified the T. equi DNA
      extracted from the organs of an experimentally infected horse. This study further
      validates LAMP as an alternative molecular diagnostic tool, which can be used in
      the diagnosis of early infections of equine piroplasmosis and together with PCR
      can also be used as supplementary methods during post-mortems.

PMID- 17216489
TI  - Use of a 203 alphaalpha fragment of Tc-PDI to detect IgA activity during
      infection by Teladorsagia circumcincta in sheep.
AB  - The objectives of this study are to find an appropriate ELISA technique to
      monitor IgA activity during infection by Teladorsagia circumcincta in sheep as
      well as to identify the degree of resistance to the infection. Previous studies
      have shown the relationship between IgA in infected sheep and the resistance to
      the infection. In this study, the titre of IgA in resistant and susceptible
      infected ewes was tested in blood, nasal secretions and saliva. ELISAs were
      carried out against somatic antigen from L4 and against a 203 amino acid fragment
      of a recombinant protein disulphide isomerase of T. circumcincta (Tc-PDI). The
      results showed that, in general, the titres of IgA against a fragment of a Tc-PDI
      were lower than against the somatic antigen. These lower levels are clearly shown
      in blood samples and nasal secretions in contrast to saliva samples where the
      titre reached higher values testing the IgA against Tc-PDI. This could be due to
      the fact that, in the detection of IgA against Tc-PDI, the antibody-antigen
      reaction is more specific than against the whole somatic antigen. To
      differentiate between resistant and susceptible animals, the significant
      differences were more present with the somatic antigen. Nevertheless, the ELISA
      technique using the somatic antigen cannot be standardized, and the antigen
      antibody reactions are more unspecific; therefore, the recombinant Tc-PDI could
      be a better option.

PMID- 17216490
TI  - Molecular characterization the YABBY gene family in Oryza sativa and expression
      analysis of OsYABBY1.
AB  - Members of the YABBY gene family have a general role that promotes abaxial cell
      fate in a model eudicot, Arabidopsis thaliana. To understand the function of
      YABBY genes in monocots, we have isolated all YABBY genes in Oryza sativa (rice),
      and revealed the spatial and temporal expression pattern of one of these genes,
      OsYABBY1. In rice, eight YABBY genes constitute a small gene family and are
      classified into four groups according to sequence similarity, exon-intron
      structure, and organ-specific expression patterns. OsYABBY1 shows unique spatial
      expression patterns that have not previously been reported for other YABBY genes,
      so far. OsYABBY1 is expressed in putative precursor cells of both the mestome
      sheath in the large vascular bundle and the abaxial sclerenchyma in the leaves.
      In the flower, OsYABBY1 is specifically expressed in the palea and lemma from
      their inception, and is confined to several cell layers of these organs in the
      later developmental stages. The OsYABBY1-expressing domains are closely
      associated with cells that subsequently differentiate into sclerenchymatous
      cells. These findings suggest that the function of OsYABBY1 is involved in
      regulating the differentiation of a few specific cell types and is unrelated to
      polar regulation of lateral organ development.

PMID- 17216491
TI  - Cloning and characterization of the ribosomal protein L3 (RPL3) gene family from
      Triticum aestivum.
AB  - Plant pathogenic fungi of the genus Fusarium can cause severe diseases on small
      grain cereals and maize. The contamination of harvested grain with Fusarium
      mycotoxins is a threat to human and animal health. In wheat production of the
      toxin deoxynivalenol (DON), which inhibits eukaryotic protein biosynthesis, is a
      virulence factor of Fusarium, and resistance against DON is considered to be part
      of Fusarium resistance. Previously, single amino acid changes in RPL3 (ribosomal
      protein L3) conferring DON resistance have been described in yeast. The goal of
      this work was to characterize the RPL3 gene family from wheat and to investigate
      the potential role of naturally existing RPL3 alleles in DON resistance by
      comparing Fusarium-resistant and susceptible cultivars. The gene family consists
      of three homoeologous alleles of both RPL3A and RPL3B, which are located on
      chromosomes 4A (RPL3-B2), 4B (RPL3-B1), 4D (RPL3-B3), 5A (RPL3-A3), 5B (RPL3-A2)
      and 5D (RPL3-A1). Alternative splicing was detected in the TaRPL3-A2 gene.
      Sequence comparison revealed no amino acid differences between cultivars
      differing in Fusarium resistance. While using developed SNP markers we
      nevertheless found that one of the genes, namely, TaRPL3-A3 mapped close to a
      Fusarium resistance QTL (Qfhs.ifa-5A). The potential role of the RPL3 gene family
      in DON resistance of wheat is discussed.

PMID- 17216492
TI  - Validation of in silico-predicted genic SNPs in white clover (Trifolium repens
      L.), an outbreeding allopolyploid species.
AB  - White clover (Trifolium repens L.) is an obligate outbreeding allotetraploid
      forage legume. Gene-associated SNPs provide the optimum genetic system for
      improvement of such crop species. An EST resource obtained from multiple cDNA
      libraries constructed from numerous genotypes of a single cultivar has been used
      for in silico SNP discovery and validation. A total of 58 from 236 selected
      sequence clusters (24.5%) were fully validated as containing polymorphic SNPs by
      genotypic analysis across the parents and progeny of several two-way pseudo
      testcross mapping families. The clusters include genes belonging to a broad range
      of predicted functional categories. Polymorphic SNP-containing ESTs have also
      been used for comparative genomic analysis by comparison with whole genome data
      from model legume species, as well as Arabidopsis thaliana. A total of 29 (50%)
      of the 58 clusters detected putative ortholoci with known chromosomal locations
      in Medicago truncatula, which is closely related to white clover within the
      Trifolieae tribe of the Fabaceae. This analysis provides access to translational
      data from model species. The efficiency of in silico SNP discovery in white
      clover is limited by paralogous and homoeologous gene duplication effects, which
      are resolved unambiguously by the transmission test. This approach will also be
      applicable to other agronomically important cross-pollinating allopolyploid plant
      species.

PMID- 17216493
TI  - Heterogeneity in expression of the Escherichia coli colicin K activity gene cka
      is controlled by the SOS system and stochastic factors.
AB  - Phenotypic diversity provides populations of prokaryotic and eukaryotic organisms
      with the flexibility required to adapt to and/or survive environmental
      perturbations. Consequently, there is much interest in unraveling the molecular
      mechanisms of heterogeneity. A classical example of heterogeneity in Escherichia
      coli is the subset (3%) of the population that expresses the colicin K activity
      gene (cka) upon nutrient starvation. Here, we report on the mechanism underlying
      this variable response. As colicin synthesis is regulated by the LexA protein,
      the central regulator of the SOS response, we focused on the role of LexA and the
      SOS system in the variable cka expression. Real-time RT-PCR showed that the SOS
      system, without exogenous DNA damage, induces moderate levels of cka expression.
      The use of cka-gfp fusions demonstrated that modification of the conserved LexA
      boxes in the cka promoter region affected LexA binding affinity and the
      percentage of cka-gfp expressing cells in the population. A lexA-gfp fusion
      showed that the lexA gene is highly expressed in a subset of bacteria.
      Furthermore, cka-gfp fusions cloned into higher copy plasmid vectors increased
      the percentage of cka-gfp positive bacteria. Together, these results indicate
      that the bistability in cka expression in the bacterial population is determined
      by (1) basal SOS activity, (2) stochastic factors and possibly (3) the interplay
      of LexA dimers at cka operator. Other LexA regulated processes could exhibit
      similar regulation.

PMID- 17216494
TI  - Genetic variation in tumor necrosis factor and lymphotoxin-alpha (TNF-LTA) and
      breast cancer risk.
AB  - Tumor necrosis factor (TNF) is critical to regulation of inflammation. Genetic
      variation in the promoter region of TNF has been associated with expression
      differences, and a range of auto-immune, infectious, and oncologic diseases. We
      analyzed eight common single nucleotide polymorphisms (SNPs) (rs746868, rs909253,
      rs1799964, rs1800630, rs1800750, rs1800629, rs361525, and rs1800610) to capture
      most of the genetic variation in TNF in addition to SNPs in lymphotoxin-alpha
      (LTA), a pro-inflammatory cytokine in linkage disequilibrium with the TNF
      promoter region. SNPs were genotyped in a USA population-based case-control study
      (3,318 cases, 2,841 controls). Promising results were followed-up in an
      independent population-based case-control study in Poland (2,228 cases, 2,378
      controls). In both studies, women carrying the variant allele of rs361525 were at
      elevated breast cancer risk compared to the GG genotype (per allele OR = 1.18,
      95% CI 1.04-1.35; P for trend = 0.008). Other SNPs were not significantly
      associated with breast cancer risk. Haplotype analyses did not reveal any
      additional associations between TNF and breast cancer risk. Data from 5,269 cases
      and 4,982 controls suggested that the rs361525 A allele, located in the TNF
      promoter region, was associated with a modest increase in breast cancer risk.
      Additional studies are required to replicate these findings and to determine
      whether rs361525 is a causative SNP or is a marker of a causative SNP.

PMID- 17216496
TI  - Distal RTA with nerve deafness: clinical spectrum and mutational analysis in five
      children.
AB  - Distal renal tubular acidosis (RTA) with nerve deafness is caused by mutations in
      the ATP6V1B1 gene causing defective function of the H+ -ATPase proton pump. We
      report five acidotic children (four males) from four unrelated families: blood pH
      7.21-7.33, serum bicarbonate 10.8-14.7 mEq/l, minimum urinary pH 6.5-7.1 and
      fractional excretion of bicarbonate in the presence of normal bicarbonatemia 1.1
      5.7%. Growth retardation and nephrocalcinosis, but not hypercalciuria, were
      common presenting manifestations. Hearing was normally preserved in one of the
      patients whose sister was severely deaf. One child was homozygous for a known
      mutation in exon 1: C>T (R31X). Three children were homozygous for a splicing
      mutation, intron 6 + 1G>A. The other patient was a compound heterozygote, having
      this mutation and a previously unreported mutation in exon 10: G>A (E330K). Our
      report shows that hearing loss is not always present in the syndrome of distal
      renal tubular acidosis with nerve deafness and the absence of hypercalciuria at
      diagnosis and describes a new mutation responsible for the disease in the
      ATP6V1B1 gene.

PMID- 17216495
TI  - CYP19A1 polymorphisms are associated with bone mineral density in Chinese men.
AB  - Aromatase-dependent biosynthesis of estrogen plays an important role in
      maintenance of the male skeleton, and Cytochrome p450 aromatase is the key enzyme
      to catalyze the conversion of androgen precursors to estrogens. We investigated
      the association of polymorphisms in the CYP19A1 gene and bone mineral density in
      a Chinese cohort. 2392 extreme low femoral neck BMD cases or extreme high femoral
      neck BMD controls were selected from a population-based cohort and genotyped for
      eight SNPs in the CYP19A1 gene. Significant associations for rs17703883,
      rs12594287 and rs16964201 SNPs with BMD were found in men only. Men with TC/CC
      genotypes in the rs17703883 SNP had a 1.5 times higher risk of having extreme low
      femoral neck BMD (P = 0.003, empirical P value = 0.05), and decreased BMDs at
      total body (P = 0.004, empirical P value = 0.07) and total hip (P = 0.003,
      empirical P value = 0.05). Men carrying AA/AG genotypes in the rs12594287 SNP had
      a 30% reduced risk of having extreme low femoral neck BMD (P = 0.007, empirical P
      value = 0.12), and increased BMDs at total body (P = 0.0009, empirical P value =
      0.018) and total hip (P = 0.001, empirical P value = 0.02). Men carrying TT/TC
      genotypes in the rs16964201 SNP had a 40% reduced risk of having extreme low
      femoral neck BMD (P = 0.005, empirical P value = 0.087), and increased BMDs at
      total body (P = 0.0001, empirical P value = 0.002) and total hip (P = 0.0006,
      empirical P value = 0.012). Haplotype analysis showed that the G-C-T-A-T
      haplotype was significantly related to higher BMD. Our finding suggests that
      genetic variations in the CYP19A1 gene are significantly associated with BMD at
      different skeletal sites in adult men, but not in women.

PMID- 17216497
TI  - Darbepoetin, effective treatment of anaemia in paediatric patients with chronic
      renal failure.
AB  - Darbepoetin alpha (DA) is a unique long-acting treatment for anaemia in patients
      with chronic renal failure (CRF). This study assessed the mean dose of DA to
      achieve and maintain haemoglobin (Hb) levels between 11 g/dl and 13 g/dl in CRF
      children aged 11 years to 18 years. This observational, prospective study was
      conducted in 39 patients treated with DA. Twenty-nine patients were switched from
      recombinant human erythropoietin (r-HuEPO), and ten patients were naive to r
      HuEPO. Naive patients received initial doses of 0.45 microg/kg of DA. Switched
      patients received a dose adjusted to the prior dose of r-HuEPO (200 IU r-HuEPO:1
      microg DA). Among the switched patients, 79.3% received dialysis. No naive
      patients underwent dialysis. Overall, 74% of patients showed increased Hb level,
      with a mean value of 11.6 +/- 1.6 g/dl, using a mean DA dose of 0.63 +/- 0.48
      microg/kg per week, and 66.7% patients reached the target Hb level. Hb increased
      in naive patients from 9.5 (95% CI: 7.7, 11.4) to 11.7 (95% CI: 10.9, 12.6) g/dl
      and in switched patients from 11.1 (95% CI: 10.6, 11.5) to 11.5 (95% CI: 10.8,
      12.2) g/dl). Higher doses of DA were needed in the "switched" than in the "naive"
      patients to maintain Hb levels over 11 g/dl, respectively 0.73 (95% CI: 0.54,
      0.92) and 0.34 (95% CI: 0.16, 0.52) microg/kg per week. Our results indicate the
      doses of DA necessary to treat CRF patients aged 11 years to 18 years. DA was an
      effective treatment to stabilise CRF patients at extended dosing intervals.

PMID- 17216499
TI  - Plant responsiveness to mycorrhizas differs from dependence upon mycorrhizas.
AB  - Soil phosphorus response curves of plants with and without mycorrhizas reflect
      two different, but complementary, phenomena. The first, plant responsiveness to
      mycorrhizas, is represented by the difference in growth between plants with and
      without mycorrhizas at any designated level of phosphorus availability. This is
      also a measure of mycorrhizal fungus effectiveness. The second, the lowest level
      of phosphorus availability at which plants can grow without mycorrhizas, is here
      termed dependence upon mycorrhizas. The latter definition differs from
      conventional usage which fails to distinguish dependence from responsiveness.
      Sigmoid curves generated by the three-parameter, logistic equation generally can
      model the responses of plants to mycorrhizas and phosphorus addition and can be
      used to assess responsiveness, effectiveness, and dependence. Such curves reveal
      that plant responsiveness or fungus effectiveness determined at a single level of
      phosphorus availability may be misleading when used to compare different host
      species' intrinsic capacities to respond to different mycorrhizal fungus species.
      Instead, the same relative position should be evaluated among phosphorus response
      curves for different species combinations. Dependence of a plant species known to
      benefit from mycorrhizas can be assessed with reference to only the phosphorus
      response curve of plants without mycorrhizas. Dependence is a constitutive
      property of plant species that can be used to classify them as facultatively or
      obligately mycotrophic. Dependence is a plant attribute upon which natural
      selection can act, but responsiveness and effectiveness cannot be selected
      directly because they are emergent properties of the interaction between plant
      and fungus species.

PMID- 17216498
TI  - Morphological and molecular evidence supporting an arbutoid mycorrhizal
      relationship in the Costa Rican paramo.
AB  - This study examines evidence for a particular arbutoid mycorrhizal interaction in
      paramo, a high-altitude neotropical ecosystem important in hydrological
      regulation but poorly known in terms of its fungal communities. Comarostaphylis
      arbutoides Lindley (Ericaceae) often forms dense thickets in Central American
      paramo habitats. Based on phylogenetic classification, it has been suggested that
      C. arbutoides forms arbutoid mycorrhizae with diverse Basidiomycetes and
      Ascomycetes; however, this assumption has not previously been confirmed. Based on
      field data, we hypothesized an arbutoid mycorrhizal association between C.
      arbutoides and the recently described bolete Leccinum monticola Halling & G.M.
      Mueller; in this study, we applied a rigorous approach using anatomical and
      molecular data to examine evidence for such an association. We examined root
      samples collected beneath L. monticola basidiomes for mycorrhizal structures, and
      we also compared rDNA internal transcribed spacer (ITS) sequences between
      mycorrhizal root tips and leaf or basidiome material of the suspected symbionts.
      Root cross sections showed a thin hyphal sheath and intracellular hyphal coils
      typical of arbutoid mycorrhizae. DNA sequence comparisons confirmed the identity
      of C. arbutoides and L. monticola as the mycorrhizal symbionts. In addition, this
      paper provides additional evidence for the widespread presence of minisatellite
      like inserts in the ITS1 spacer in Leccinum species (including a characterization
      of the insert in L. monticola) and reports the use of an angiosperm-specific ITS
      primer pair useful for amplifying plant DNA from mycorrhizal roots without co
      amplifying fungal DNA.

PMID- 17216500
TI  - Respiratory responses of arbuscular mycorrhizal roots to short-term alleviation
      of P deficiency.
AB  - Arbuscular mycorrhizal (AM) root respiration can impose a respiratory sink on
      host reserves under low P conditions, but it is not known how AM roots respond to
      short-term supply of sufficient P. Therefore, the effect of P stress alleviation
      on the respiration of AM roots was investigated in 5-week-old tomato plants.
      Plants were inoculated with Glomus mosseae in sand culture and grown
      hydroponically in a low P (2 microM) nutrient medium for 3 weeks. P stress was
      alleviated by the supply of 2 mM P for 72 h. With P stress alleviation, the
      improved root P status coincided with a decline in AM fungal activity and a
      reduction in root CO2 and O2 fluxes of the AM plants. During P stress
      alleviation, the AM roots had lower concentrations of organic acids, derived from
      root-zone CO2 assimilation, in their root exudates. These results show that short
      term alleviation of low P conditions in AM roots rapidly affects AM fungal
      symbiont activity, AM root respiration, and root-zone CO2-derived organic acid
      metabolism.

PMID- 17216501
TI  - Localization of proton-ATPase genes expressed in arbuscular mycorrhizal tomato
      plants.
AB  - In arbuscular mycorrhizal symbioses, solutes such as phosphate are transferred to
      the plant in return for photoassimilates. The uptake mechanism is probably
      facilitated by a proton gradient generated by proton H(+)-ATPases. We
      investigated expression of Lycopersicon esculentum Mill. H(+)-ATPases in
      mycorrhizal and non-mycorrhizal plants to determine if any are specifically
      regulated in response to colonization. Tissue expression and cellular
      localization of H(+)-ATPases were determined by RNA gel blot analysis and in situ
      hybridization of mycorrhizal and non-mycorrhizal roots. LHA1, LHA2, and LHA4 had
      high levels of expression in roots and were expressed predominantly in epidermal
      cells. LHA1 and LHA4 were also expressed in cortical cells containing arbuscules.
      The presence of arbuscules in root sections was correlated with lower levels of
      expression of these two isoforms in the epidermis. These results suggest that
      LHA1 and LHA4 expression is decreased in epidermal cells located in regions of
      the root that contain arbuscules. This provides evidence of differential
      regulation between molecular mechanisms involved in proton-coupled nutrient
      transfer either from the soil or fungus to the plant.

PMID- 17216502
TI  - Detection of extracellular protease activity in different species and genera of
      ectomycorrhizal fungi.
AB  - In northern forest ecosystems, most soil nitrogen (N) is in organic form and
      forest trees are largely dependent on ectomycorrhizal (ECM) fungi and their
      degradative abilities for N uptake. The ability of ECM fungi to acquire N from
      organic substrates should, therefore, be a widespread trait given its ecological
      importance. However, little is known about the degradative abilities of most ECM
      fungi as they remain untested due to problems of isolation or extremely slow
      growth in pure culture. In this paper, we present data on extracellular protease
      activity of 32 species of ECM fungi, most of which have not previously been
      cultured. Milk powder plates and zymograms were compared for detecting protease
      activity in these intractable species. In total, 29/32 of the species produced
      extracellular protease activity, but detection was method dependent. Growth on
      milk powder plates detected protease activity in 28 of 32 species, while
      zymograms only detected proteases in Amanita muscaria, Russula chloroides,
      Lactarius deterrimus and Lactarius quieticolor. The study supports the hypothesis
      that protease excretion is a widespread physiological trait in ECM fungi and that
      this ability is of considerable significance for nitrogen uptake in forest
      ecosystems.

PMID- 17216503
TI  - [Treatment of oncology patients in the final stadium of disease by prehospital
      emergency physicians].
AB  - BACKGROUND: Presently and even more in the near future more cancer patients will
      be treated at home especially in the final stage of their disease. For this
      reason the prehospital emergency system will be confronted with the specific
      needs of these patients. Palliative care is not part of the German model of post
      graduate training regulations for emergency medicine and palliative care teams
      (PCT) are only involved in the treatment of cancer patients in emergency
      situations. METHODS: Over a 12-month period we retrospectively analysed all
      emergency cases that had been categorised as final cancer stage at 2 emergency
      sites (one air-based, the other ground-based) involving physicians in an out-of
      hospital setting. We analysed all cases for indications of emergency call,
      prehospital treatment and involvement of a PCT in the treatment of symptoms.
      RESULTS: For this period we analysed 2,765 emergency documents and identified
      more than 2.5% as emergency calls by cancer patients or their relatives (the
      majority of patients had been in the final stage of the disease). Most emergency
      calls occurred at times when no general practitioner was on duty and acute
      dyspnoea (42.7%) was the prominent diagnosis. After emergency treatment 61.8%
      patients had been admitted to hospital. In most settings a PCT was not involved
      in the treatment of palliative care patients or their relatives (92.7%).
      CONCLUSIONS: Our data demonstrate that care of cancer patients in the final stage
      of the disease is relevant in emergency medicine. These patients are in need of
      help based on principles of palliative care. Under these circumstances
      cooperation of the medical disciplines (emergency and palliative medicine)
      concerned seems to be necessary. This may increase the possibility for patients
      to stay at home for the last days of their life. Because of this we are convinced
      that basic knowledge of palliative care should be integrated into the German
      model of post-graduate training regulations for emergency care. Combining parts
      of the curricula (palliative and emergency medicine) it would be possible for
      emergency physicians to guide their treatment by the ideas and strategies of
      palliative care. But we are also convinced that the system of PCT should increase
      and become more involved in prehospital care in emergency cases of palliative
      care patients.

PMID- 17216504
TI  - [Perioperative hemostasis management].
AB  - Hemostasis management plays an important role in surgery. Anti-platelet drugs and
      oral anticoagulants are taken by an increasing number of patients. Perioperative
      management must take into account bleeding as well as thromboembolic risks when
      withholding these medications. Patients with inherited or acquired hemostatic
      disorders should receive interdisciplinary care in order to optimise
      perioperative substitution therapy. For the diagnosis of acquired coagulopathy
      secondary to massive bleeding, point of care tests have been introduced that
      should help focus substitution therapy in emergency situations. However,
      physicians should be aware of the limitations of these methods, and a full
      diagnostic workup should be done in order to uncover hemorrhagic diatheses not
      detected by point of care testing.

PMID- 17216505
TI  - [Pseudovesicles on the palms of the hands and the soles of the feet].

PMID- 17216506
TI  - [Internists--Update 2006].

PMID- 17216508
TI  - [Under what conditions is subcutaneous administration of fluid indicated].

PMID- 17216507
TI  - [Metabolic syndrome. Origin within the central nervous system?].
AB  - All efforts based on current concepts of obesity have failed to stop the
      epidemic. Hitherto, the question of body mass regulation focused on regulatory
      principles centered on the hypothalamus. We present the novel view that the brain
      (cerebral hemispheres, hypothalamus) requests energy in an active manner from the
      body (allocation) or the environment (food intake). Disruption of one of the
      cerebral energy request pathways is highly relevant to the development of
      obesity, metabolic syndrome and diabetes type 2. We have reviewed the literature
      from this new perspective, putting the brain as the focal midpoint of all
      metabolic activity.

PMID- 17216509
TI  - [Diagnostic imaging of liver tumours. Current status].
AB  - Nowadays, contrast enhanced ultrasound (CEUS) is an imaging technique equivalent
      to multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI)
      for the detection and characterization of focal liver lesions. These methods have
      comparable sensitivity and specificity in differentiating a liver lesion as
      "benign" or "malignant". For benign lesions, CEUS is the recommended method of
      the choice. In unclear cases, or if CEUS is not available, MRI or CT are the
      methods of the second choice. If a benign tumor remains unclear, then a needle
      biopsy is recommended. In the case of a malignant tumor, it is necessary to use a
      second imaging technique besides CEUS. In addition to the detection and
      characterization of a liver tumor, CT and MRI provide information on the
      extrahepatic spread of a tumor, particularly into the lung or retroperitoneum.
      The rapid development of surgical and interventional approaches requires accurate
      information on the character and number of malignant liver lesions. Therefore,
      the combined use of CEUS and MDCT or MRI currently represents the most modern and
      optimal standard of imaging. The standardization of CT and MRI protocols has
      increased the general diagnostic level of these images. Adequate training and a
      certificate for the use of CEUS is recommended in order to maintain the high
      diagnostic level of this method (EFSUMB guide lines). An optimal
      interdisciplinary imaging strategy for focal liver lesions minimises unnecessary
      invasive or potentially harmful imaging and reduces health costs.

PMID- 17216510
TI  - [Cardiogenic shock after adrenalectomy for pheochromocytoma].
AB  - A 56 year old patient underwent left-sided adrenalectomy for a benign
      pheochromocytoma. During surgery, he developed a hypertensive crisis while the
      tumor was being manipulated. Postoperatively, the patient became hypotensive and
      developed cardiogenic shock. He remained ventilated and intubated. In the
      subsequent echocardiography a severely impaired left ventricular function with
      apical akinesia was observed, while the preoperative echocardiogram was normal.
      Acute coronary angiography was performed which showed no significant stenoses in
      the coronary arteries. Apical ballooning was seen in the left ventricular
      angiogram. On the second postoperative day, echocardiography showed an improved
      left ventricular function which was almost normalized within the next week.
      Catecholamine release during a left-sided adrenalectomy for a benign
      pheochromocytoma was associated with Takotsubo cardiomyopathy complicated by
      cardiogenic shock.

PMID- 17216512
TI  - [Palliation for respiratory syndrome].
AB  - Respiratory symptoms such as dyspnea, coughing, bronchorrhea, hemoptysis and
      death rattle are a common problem in palliative medicine. Their prevalence
      increases markedly in terminal phase oncological patients. In such cases, new
      therapeutic methods with lower toxicity and well documented efficiency in the
      control of respiratory syndrome should be considered.

PMID- 17216511
TI  - [Optical imaging of fluorescence in the near infrared. From passive to
      enzymatically activated contrast medium].
AB  - The molecular imaging of specific targets using optical methods is currently
      possible in vivo, in part due to the advances in imaging modalities
      (epifluorescence, fluorescent endoscopy, fluorescence mediated tomography,
      intravital fluorescence microscopy), and in part due to the development of better
      contrast media. These are composed of a suitable fluorochrome, usually with
      emission in the near infrared due to tissue penetration, as well as by molecular
      specific contrast media from ligands. The latest generation of contrast media is
      not fluorescent in its unactivated state. Fluorescence first occurs after contact
      with certain (e.g. disease specific) enzymes by which a minimally unspecific
      fluorescent background as well as molecular specificity is made possible.

PMID- 17216513
TI  - [Induction of urothelial carcinoma due to chronic arsenic ingestion? A
      occupational medicine-toxicological excursion].
AB  - Whether chronic intoxication with arsenic can induce cancer of the urinary tract
      is an important question in urology and occupational medicine. Here, we consider
      potential exposure, and discuss the epidemiology and toxicology of arsenic. In
      addition, we conceptualize a possible strategy for clinical procedures.

PMID- 17216514
TI  - [Burkitt's and Burkitt-like lymphoma. Molecular definition and value of the World
      Health Organisation's diagnostic criteria].
AB  - Among aggressive mature B-cell lymphomas, a reproducible morphological and
      immunohistological distinction between Burkitt's lymphoma and diffuse large B
      cell lymphoma (centroblastic variant) is impossible in a substantial number of
      cases. The German reference centres for hematopathology collected 220
      retrospective cases of aggressive mature B-cell lymphoma whose classification
      according to the current World Health Organisation criteria was reviewed. Gene
      expression analysis (Affymetrix) was performed in all cases and chromosomal
      translocations were determined using fluorescence in situ hybridization.
      Chromosomal losses and gains were analysed by matrix comparative genomic
      hybridisation and clinical data were successfully collected for most patients.
      The application of a novel bioinformatics method led to the identification of a
      stable and reproducible gene expression signature specific for Burkitt's
      lymphoma. A total of 44 cases were identified by this molecular signature
      [designated molecular Burkitt's lymphoma (mBL)]. These molecular Burkitt's
      lymphomas showed the morphology and immunohistology of classical or atypical
      Burkitt's lymphoma cases in 29 instances. However, 15 of the molecular Burkitt's
      lymphoma cases had the morphology of diffuse large B-cell lymphoma or could not
      be further specified. All molecular Burkitt's lymphomas showed an expression of
      BCL-6 and CD10, but a MYC translocation was not demonstrable in more than 10% of
      cases. Of significance is that more than 20% of the molecular Burkitt's lymphomas
      expressed BCL-2, although weakly in most instances. Our data demonstrate that:
      (1) the morphological, immunophenotypical and genetic spectrum of Burkitt's
      lymphoma is broader than previously expected, and (2) our molecular Burkitt's
      lymphoma signature enables a more precise and extended definition this lymphoma.

PMID- 17216515
TI  - [The central island tongue flap for the reconstruction of the anterior floor of
      the mouth].
AB  - BACKGROUND: There are several techniques described for the reconstruction of the
      anterior floor of mouth after tumour surgery. Here, we point out the advantages
      of the central island tongue flap for this indication. PATIENTS AND METHODS: We
      report on 20 patients with medium sized defect in the anterior floor of mouth,
      which was reconstructed with the central island tongue flap. Besides this
      surgical technique, we discuss the results of oral rehabilitation after a follow
      up period of at least 3 months. RESULTS: There was now flap necrosis or loss, and
      the median time for flap formation was less than 45 min. In the follow-up we
      found successful oral rehabilitation in speech and swallowing.

PMID- 17216516
TI  - An integrated approach for the comparative analysis of a multigene family: the
      nicotianamine synthase genes of barley.
AB  - Recent genomic projects reveal that about half of the gene repertoire in plant
      genomes is made up by multigene families. In this paper, a set of structural and
      phylogenetic analyses have been applied to compare the differently sized
      nicotianamine synthase (NAS) gene families in barley and rice. Nicotianamine acts
      as a chelator of iron and other heavy metals and plays a key role in uptake,
      phloem transport and cytoplasmic distribution of iron, challenging efforts for
      the breeding of iron-efficient crop plants. Nine barley NAS genes have been
      mapped, and co-linearity of flanking genes in barley and rice was determined. The
      combined analyses reveal that the NAS multigene family members in barley
      originated through at least one duplication event that occurred before the
      divergence of rice and barley. Additional duplications appear to have occurred
      within each of the species. Although we detected no evidence for positive
      selection of recently duplicated genes within species, codon-based tests revealed
      evidence for positive selection having contributed to the divergence of some
      amino acids. The integrated comparative and phylogenetic analysis improved our
      current view of NAS gene family evolution, might facilitate the functional
      characterization of individual members and is applicable to other multigene
      families.

PMID- 17216517
TI  - Insect nicotinic acetylcholine receptor gene families: from genetic model
      organism to vector, pest and beneficial species.
AB  - Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in
      the insect nervous system and are targets of a major group of insecticides, the
      neonicotinoids. Analyses of genome sequences have shown that nAChR gene families
      remain compact in diverse insect species, when compared to their mammalian
      counterparts. Thus, Drosophila melanogaster and Anopheles gambiae each possess 10
      nAChR genes while Apis mellifera has 11. Although these are among the smallest
      nAChR gene families known, receptor diversity can be considerably increased by
      alternative splicing and mRNA A-to-I editing, thereby generating species-specific
      subunit isoforms. In addition, each insect possesses at least one highly
      divergent nAChR subunit. Species-specific subunit diversification may offer
      promising targets for future rational design of insecticides that act on
      particular pests while sparing beneficial insects. Electrophysiological studies
      on cultured Drosophila cholinergic neurons show partial agonist actions of the
      neonicotinoid imidacloprid and super-agonist actions of another neonicotinoid,
      clothianidin, on native nAChRs. Recombinant hybrid heteromeric nAChRs comprising
      Drosophila Dalpha2 and a vertebrate beta2 subunit have been instructive in
      mimicking such actions of imidacloprid and clothianidin. Unitary conductance
      measurements on native nAChRs indicate that more frequent openings of the largest
      conductance state may offer an explanation for the superagonist actions of
      clothianidin.

PMID- 17216518
TI  - Pattern VEPs before and after idiopathic epiretinal membrane removal.
AB  - Pattern visual evoked potentials (pVEPs) were used to assess the visual function
      before, and 1 and 6 months after removal of an idiopathic epiretinal membrane
      (ERM) from eight eyes. All patients underwent a standard three-port pars plana
      vitrectomy to remove the ERM removal and cataract surgery. pVEPs were elicited by
      check sizes of 15', 30', 60', and 120' with a reversal rate of 2 reversals/s. One
      hundred responses were averaged with an analysis time of 300 ms. The amplitude
      ratio (affected eye/fellow eye) of the P100 component were significantly larger
      at 6 months with smaller check sizes, and the increase was accompanied by an
      improvement of the VA. The mean peak latency of P100 did not change significantly
      for all check sizes. We conclude that the improvement of the P100 amplitude with
      smaller check sizes resulted from the recovery of visual function after the ERM
      removal.

PMID- 17216520
TI  - Neuroendovascular magnetic navigation: clinical experience in ten patients.
AB  - INTRODUCTION: The magnetic navigation system consists of an externally generated
      magnetic field that is used to control and steer a magnetically tipped
      microguidewire. The goal of this study was to demonstrate that the use of the
      magnetic navigation system and its magnetic microguidewire is feasible and safe
      in all types of neuroendovascular procedures. METHODS: A magnetic navigation
      system is an interventional workstation that combines a biplanar fluoroscopy
      system with a computer-controlled magnetic field generator to provide both
      visualization and control of a magnetically activated endovascular
      microguidewire. Ten consecutive patients underwent a variety of neuroendovascular
      procedures using the magnetic guidance system and magnetic microguidewire. All
      patients presented with a neurovascular disease that was suitable for
      endovascular treatment. Multiple different devices and embolic agents were used.
      RESULTS: Of the ten patients, three were male and seven female. Their mean age
      was 53.9 years. The predominant neurovascular condition was the presence of
      intracranial aneurysm (nine patients). One patient had a left mandibular
      arteriovenous malformation. All treatments were successfully performed on the
      magnetic navigation system suite. The magnetic navigation system and the magnetic
      microguidewire allowed safe and accurate endovascular navigation allowing
      placement of the microcatheters in the desired location. There were no
      neurological complications or death in our series. CONCLUSION: The use of the
      magnetic navigation system and the magnetic microguidewire in the endovascular
      treatment of patients with neurovascular diseases is feasible and safe.

PMID- 17216521
TI  - Comment on the paper entitled: "Percutaneous drainage as the treatment of choice
      for neonatal ovarian cysts".

PMID- 17216522
TI  - The computer-assisted sequential lateral soft-tissue release in total knee
      arthroplasty for valgus knees.
AB  - Soft-tissue management is a critical factor in total knee arthroplasty,
      especially in valgus knees. The stepwise release has been based upon surgeon's
      experience. Computer-assisted surgery has gained increasing scientific interest
      in recent times and allows the intraoperative measurement of leg axis and gap
      size in extension and flexion. We therefore aimed to analyse the effect of
      sequential lateral soft-tissue release and the resulting change in the a.p. limb
      axis on the one hand and the tibiofemoral gaps on the other hand in extension as
      well as in flexion in eight cadaveric knees. Measurements were obtained using a
      CT-free navigation system. In extension the highest increase compared to the
      previous release step was found for the first (iliotibial band, P = 0.002),
      second (popliteus muscle, P = 0.0003), third (LCL, 0.007) and the sixth (entire
      PCL, P = 0.001) release step. In 90 degrees flexion all differences of the
      lateral release steps were statistically significant (P < 0.004). Massive
      progression of the lateral gap in flexion was found after the second (popliteus
      muscle, P = 0.004) and third (LCL, 0.007) release step. Computer-assisted surgery
      allows measurement of the effect of each release step of the sequential lateral
      release sequence and helps the surgeon to better assess the result.

PMID- 17216523
TI  - Accuracy of direct magnetic resonance arthrography in the diagnosis of triangular
      fibrocartilage complex tears of the wrist.
AB  - The aim of this study was to assess the value of direct magnetic resonance (MR)
      arthrography of the wrist for detecting full-thickness tears of the triangular
      fibrocartilage complex (TFCC). Twenty-four consecutive patients who had ulnar
      sided wrist pain and clinical suspicion of TFCC tear were included in the study.
      All patients underwent direct MR arthrography and then wrist arthroscopy, and the
      results of MR arthrography were compared with the arthroscopic findings. The
      positive predictive value of MR arthrography in detecting TFCC full-thickness
      tear was 0.95, and the negative predictive value was 0.50. The sensitivity of MR
      arthrography in detecting a TFCC full-thickness tear was 74% (15/19), and
      specificity was 80% (4/5). The overall accuracy of MR arthrography in detecting a
      full-thickness tear of the TFCC in our study was 79% (19/24). We believe that
      diagnosis of tears in the TFCC by direct MR arthrography is not entirely
      satisfactory, although MR arthrography has a high positive predictive value for
      detecting TFCC tears. Negative results of MR arthrography in patients with
      clinical suspicion of TFCC tear should be interpreted with caution.

PMID- 17216524
TI  - Tuning the cochlea: wave-mediated positive feedback between cells.
AB  - Frequency analysis by the mammalian cochlea is traditionally thought to occur via
      a hydrodynamically coupled 'travelling wave' along the basilar membrane. A
      persistent difficulty with this picture is how sharp tuning can emerge. This
      paper proposes, and models, a supplementary or alternative mechanism: it supposes
      that the cochlea analyses sound by setting up standing waves between parallel
      rows of outer hair cells. In this scheme, multiple cells mutually interact
      through positive feedback of wave-borne energy. Analytical modelling and
      numerical evaluation presented here demonstrate that this can provide narrow-band
      frequency analysis. Graded cochlear tuning will then rely on the distance between
      rows becoming greater as distance from the base increases (as exhibited by the
      actual cochlea) and on the wave's phase velocity becoming slower. In effect,
      tuning is now a case of varying the feedback delay between the rows, and a prime
      candidate for a wave exhibiting suitably graded phase velocity-a short-wavelength
      'squirting wave'-is identified and used in the modelling. In this way, resonance
      between rows could supply both amplification and high Q, characteristics
      underlying the 'cochlear amplifier'-the device whose action has long been evident
      to auditory science but whose anatomical basis and mode of operation are still
      obscure.

PMID- 17216525
TI  - Brain induction in ascidian embryos is dependent on juxtaposition of FGF9/16/20
      producing and -receiving cells.
AB  - Coordinated regulation of inductive events, both spatially and temporally, during
      animal development ensures that tissues are induced at their specific positions
      within the embryo. The ascidian brain is induced in cells at the anterior edge of
      the animal hemisphere by fibroblast growth factor (FGF) signals secreted from
      vegetal cells. To clarify how this process is spatially regulated, we first
      identified the sources of the FGF signal by examining the expression of brain
      markers Hr-Otx and Hr-ETR-1 in embryos in which FGF signaling is locally
      inhibited by injecting individual blastomeres with morpholino oligonucleotide
      against Hr-FGF9/16/20, which encodes an endogenous brain inducer. The blastomeres
      identified as the inducing sources are A5.1 and A5.2 at the 16-cell stage and
      A6.2 and A6.4 at the 24-cell stage, which are juxtaposed with brain precursors at
      the anterior periphery of the embryo at the respective stages. We also showed
      that all the cells of the animal hemisphere are capable of expressing Hr-Otx in
      response to the FGF signal. These results suggest that the position of inducers,
      rather than competence, plays an important role in determining which animal cells
      are induced to become brain tissues during ascidian embryogenesis. This situation
      in brain induction contrasts with that in mesoderm induction, where the positions
      at which the notochord and mesenchyme are induced are determined mainly by
      intrinsic competence factors that are inherited by signal-receiving cells.

PMID- 17216526
TI  - Pulmonary abscess of viral-bacterial etiology in a neonate.

PMID- 17216527
TI  - Effects of temperature variation on suicide in five U.S. counties, 1991-2001.
AB  - Effects of weather variables on suicide are well-documented, but there is still
      little consistency among the results of most studies. Nevertheless, most studies
      show a peak in suicides during the spring season, and this is often attributed to
      increased temperatures. The purpose of this study is to test the relationship
      between monthly temperature and monthly suicide, independent of months or
      seasons, for five counties located across the United States. Harmonic analysis
      shows that four of the five counties display some seasonal components in the
      suicide data. However, simple linear regression shows no correlation between
      suicide and temperature, and discriminant analysis shows that monthly departure
      from mean annual suicide rates is not a useful tool for identifying months with
      temperatures that are colder or warmer than the annual average. Therefore, it
      appears that the seasonality of suicides is due to factors other than
      temperature.

PMID- 17216528
TI  - Successful treatment of cervical myelopathy with minimal morbidity by
      circumferential decompression and fusion.
AB  - Circumferential cervical decompression and fusion (CCDF) is an important
      technique for treating patients with severe cervical myelopathy. While
      circumferential cervical decompression and fusion may provide improved spinal
      cord decompression and stability compared to unilateral techniques, it is
      commonly associated with increased morbidity and mortality. We performed a
      retrospective analysis of patients undergoing CCDF at the University of
      California, San Francisco (UCSF) between January 2003 and December 2004. We
      identified 53 patients and reviewed their medical records to determine the
      effectiveness of CCDF for improving myelopathy, pain, and neurological function.
      Degree of fusion, functional anatomic alignment, and stability were also
      assessed. Operative morbidity and mortality were measured. The most common causes
      of cervical myelopathy, instability, or deformity were degenerative disease (57%)
      and traumatic injury (34%). Approximately one-fifth of patients had a prior
      fusion performed elsewhere and presented with fusion failure or adjacent-level
      degeneration. Postoperatively, all patients had stable (22.6%) or improved
      (77.4%) Nurick grades. The average preoperative and postoperative Nurick grades
      were 2.1 +/- 1.9 and 0.4 +/- 0.9, respectively. Pain improved in 85% of patients.
      All patients had radiographic evidence of fusion at last follow-up. The most
      common complication was transient dysphagia. Our average clinical follow-up was
      27.5 +/- 9.5 months. We present an extensive series of patients and demonstrate
      that cervical myelopathy can successfully be treated with CCDF with minimal
      operative morbidity. CCDF may provide more extensive decompression of the spinal
      cord and may be more structurally stable. Concerns regarding operation-associated
      morbidity should not strongly influence whether CCDF is performed.

PMID- 17216529
TI  - In vitro comparison of chlorhexidine and povidone-iodine on the long-term
      proliferation and functional activity of human alveolar bone cells.
AB  - This work reports the behaviour of osteoblastic human alveolar bone cells (first
      subculture) in the presence of chlorhexidine (CHX) and povidone-iodine (PI).
      Short contact (2 min) of 24-h cultures with CHX, at 0.12 and 0.2%, and PI, at 5
      and 10%, caused cell death within minutes; contact with 1% PI resulted in loss of
      the elongated characteristic cell shape. Cell adhesion was adversely affected at
      concentrations higher than 5 x 10(-5)% CHX or 0.05% PI. Long-term exposure to CHX
      at 10(-5) and 10(-4)% or PI at 10(-4)% had little effect on cell growth and
      caused an induction in the synthesis of alkaline phosphatase (ALP).
      Concentrations of CHX and PI similar and higher than, respectively, 5 x 10(-4)%
      or 0.05% caused dose-dependent deleterious effects. CHX affected mainly the cell
      growth, whereas the effects of PI were observed mostly in ALP production and
      matrix mineralization. Considering the levels of CHX and PI used routinely in the
      oral cavity, results suggest that CHX has a higher cytotoxicity profile than PI.
      This observation might have some clinical relevance regarding the potential
      utility of PI in the prevention of alveolar osteitis.

PMID- 17216530
TI  - Periprocedural morbidity and mortality by endovascular treatment of cerebral
      aneurysms with GDC: a retrospective 12-year experience of a single center.
AB  - Despite increasing experience and improved material, endovascular treatment of
      cerebral aneurysms still has risks linked to the technique itself and to the
      specificity of the pathology treated. The purpose of this report is to examine
      procedural technical and clinical negative events, even minimal ones, occurring
      in this type of treatment. We considered 557 procedures carried out from January
      1994 to December 2005 in 533 patients harboring 550 aneurysms. Of the patients,
      448 presented with SAH and 85 with unruptured aneurysms. All procedures were
      performed under general anesthesia. The GDC-10 system was routinely used.
      Additional devices like the balloon remodeling technique, Trispan and stents were
      also occasionally used. Every procedural complication occurring during or soon
      after treatment was registered. Endovascular treatment was completed in 539 out
      of 557 procedures. There were 18 failures (3.3%). Occlusion of the aneurysm was
      judged complete in 343 (64%), near complete in 184 (34%) and incomplete in 12
      (2%). Procedural complications occurred in 72 (13%) of the cases. The most
      frequent negative events were thromboembolisms (6.6%) and ruptures (3.9%). Other
      types (coil migration, transient occlusions of the parent vessel, dissections and
      early rebleeding) were rarer (2.5%). In the majority of cases there were no
      clinical consequences. Procedural morbidity and mortality were 1.1 and 1.8%,
      respectively. Considering the 449 procedures performed in ruptured and the 90 in
      the unruptured aneurysms separately, morbidity and mortality were 1.1 and 2.2% in
      the former group and 1.1 and 0% in the latter. Many factors influence the risk of
      complications. Being progressively aware of this and with increasing experience,
      the frequency can be limited. Negative events linked to the procedure have more
      significant serious clinical consequences in patients admitted in a critical
      clinical condition after SAH, because of the already present changes involving
      the brain parenchyma and cerebral circulation.

PMID- 17216531
TI  - Phase I study of gefitinib, irinotecan, 5-fluorouracil and leucovorin in patients
      with metastatic colorectal cancer.
AB  - PURPOSE: To determine the maximum tolerated doses (MTD), toxicities, efficacy,
      and pharmacokinetics (PK) of gefitinib combined with irinotecan, 5-fluorouracil
      (5-FU) and leucovorin (IFL) in patients with previously untreated advanced
      colorectal cancer. EXPERIMENTAL DESIGN: Starting doses were gefitinib 250 mg/day
      orally without interruption, irinotecan 100 mg/m(2) as a 90 min intravenous
      (i.v.) infusion, 5-FU 400 mg/m(2) bolus i.v. and leucovorin 20 mg/m(2) i.v. on
      days 1 and 8 of a 21-day cycle. Dose escalations involved increasing gefitinib to
      500 mg then increasing irinotecan to 125 mg/m(2) and 5-FU to 500 mg/m(2).
      RESULTS: Twenty-four patients received therapy. The starting doses proved to be
      the MTD, as attempts to increase the dose of either gefitinib or the
      chemotherapeutic agents resulted in dose-limiting toxicities. Gastrointestinal
      effects and bone marrow suppression were the principal toxicities; however, only
      1/17 (6%) patients treated with the MTD had severe (grades 3-4) diarrhea and
      severe neutropenia occurred in only two (12%) patients. Partial responses
      occurred in 10/17 patients receiving the MTD and another five had stable disease.
      Median progression-free and overall survivals were 12.2 and 26.6 months,
      respectively. In ten patients treated with the MTD, the steady-state PK of
      gefitinib was not affected by IFL nor did gefitinib appear to influence the PK of
      either irinotecan or 5-FU. CONCLUSIONS: Gefitinib can be safely combined with an
      intermittent weekly schedule of IFL. Evidence of promising activity should
      encourage further clinical evaluation of epidermal growth factor receptor
      tyrosine kinase inhibitors, such as gefitinib, combined with multiagent
      chemotherapy for metastatic colorectal cancer.

PMID- 17216532
TI  - The contribution of Gianni Bonadonna to the history of chemotherapy.
AB  - The history of cancer chemotherapy and of the discipline of medical oncology has
      been that of drug discovery. The pioneering discoveries of the early days of
      chemotherapy have allowed the development of a paradigm for drug discovery that
      persists, with modifications to the present day. This review article summarizes
      the seminal work of the Italian scientist Gianni Bonadonna on the treatment of
      breast cancer and Hodgkin's disease.

PMID- 17216533
TI  - Bilateral congenital diaphragmatic hernia and gastroschisis in a newborn: can low
      intrathoracic pressure prevent the pulmonary hypoplasia?
AB  - Congenital diaphragmatic hernia (CDH) is associated with high mortality and
      morbidity due to pulmonary hypoplasia (PH) and persistent pulmonary hypertension
      (PPH). Bilateral CDH is extremely rare with poor prognosis. It is usually
      accepted that PH in CDH is due to the herniation of abdominal viscera in the
      thorax leading to compression of the lung and preventing the normal lung
      development. On the other hand, some authors suggest that the PH occurs
      independently from the intrathoracic pressure in foetuses with CDH because of
      embryologic and genetic factors. We report a case of a newborn with bilateral CDH
      and gastroschisis born without PH, with favourable outcome. We support the
      hypothesis that a low intrathoracic pressure in patients with CDH allows an
      improved lung development.

PMID- 17216535
TI  - Purification and characterization of polygalacturonase produced by thermophilic
      Thermoascus aurantiacus CBMAI-756 in submerged fermentation.
AB  - An extracellular polygalacturonase was isolated from 5-day culture filtrates of
      Thermoascus aurantiacus CBMAI-756 and purified by gel filtration and ion-exchange
      chromatography. The enzyme was maximally active at pH 5.5 and 60-65 degrees C.
      The apparent K (m) with citrus pectin was 1.46 mg/ml and the V (max) was 2433.3
      micromol/min/mg. The apparent molecular weight of the enzyme was 30 kDa. The
      enzyme was 100% stable at 50 degrees C for 1 h and showed a half-life of 10 min
      at 60 degrees C. Polygalacturonase was stable at pH 5.0-5.5 and maintained 33% of
      initial activity at pH 9.0. Metal ions, such as Zn(+2), Mn(+2), and Hg(+2),
      inhibited 50, 75 and 100% of enzyme activity. The purified polygalacturonase was
      shown to be an endo/exo-enzyme, releasing mono, di and tri-galacturonic acids
      within 10 min of hydrolysis.

PMID- 17216534
TI  - Novel 'phage display antibodies identify distinct heparan sulfate domains in
      developing mammalian lung.
AB  - Heparan sulfate proteoglycans (HSPGs) are essential to respiratory morphogenesis
      in species as diverse as Drosophila and mice; they play a role in the regulation
      of numerous HS-binding growth factors, e.g. fibroblast growth factors. Moreover,
      an HS analogue, heparin, modulates lung growth in vitro. However, it has been
      difficult to assess the roles of specific HS structures in lung development due
      to technical barriers to their spatial localisation. Lungs from Sprague-Dawley
      rats were harvested between E15.5 and E19.5 and immediately fixed in 4 % (w/v)
      paraformaldehyde (in 0.1 M phosphate-buffered saline (PBS), pH 7.4). Lungs were
      washed in PBS, cryoprotected with 20% (w/v) sucrose (in PBS), gelatin embedded
      [7.5% (w/v) gelatin, 15% (w/v) sucrose in PBS], before being covered in Cryo-M
      Bed (Bright, Huntingdon, UK) and snap frozen at -40 degrees C. Cryosections were
      cut at 8 microm and stained with the HSPG core protein specific antibody 3G10 and
      a HS 'phage display antibody, EW4G2V. 3G10 and EW4G2V immunohistochemistry
      highlighted the presence of specific HS structures in lungs at all gestational
      ages examined. 3G10 strongly labelled airway basement membranes and the
      surrounding mesenchyme and showed weak staining of airway epithelial cells.
      EW4G2V, however, was far more selective, labelling the airway basement membranes
      only. Mesenchymal and epithelial cells did not appear to possess the HS epitope
      recognised by EW4G2V at these gestational ages. Novel 'phage display antibodies
      allow the spatial distribution of tissue HS to be analysed, and demonstrate in
      situ that distinct cellular compartments of a tissue possess different HS
      structures, possibly on the same proteoglycan core protein. These probes offer a
      new opportunity to determine the role of HS in the pathogenesis of congenital
      defects such as congenital diaphragmatic hernia (CDH), where lung development is
      aberrant, and the resulting pulmonary hypoplasia and hypertension are a primary
      cause of mortality.

PMID- 17216537
TI  - Development of microsatellite markers from tartary buckwheat.
AB  - A genomic library enriched with (gT)(n) repeats from tartary buckwheat (Fagopyrum
      tataricum) was constructed using 5'-anchored PCR for the development of
      microsattellite markers. Sequencing analysis of 5 clones from the library showed
      that they all contained microsatellites (totally 10 loci), and each was unique.
      An additional locus-specific primer was designed according to flanking sequence.
      Two of the microsatellite loci of 10 tartary buckwheat varieties were amplified
      using an anchored primer and a locus-specific primer, which revealed a clear
      polymorphic pattern. The data confirmed that the degenerate primer was reliably
      anchoring at the 5'-end of the microsatellite, and the primers developed based on
      this technology could be used for diversity analysis of tartary buckwheat.

PMID- 17216536
TI  - A cell-detaching reactor for inoculation of anchorage-dependent CHO and Vero
      cells between stepwise-expanded bioreactors.
AB  - A cell-detaching reactor was developed to collect cells growing on microcarriers
      for inoculation between stepwise-expanded bioreactors. It consisted of a
      trypsinization zone and a separation zone, which were separated by a 200-mesh
      stainless steel screen. The screen allowed the cells only to pass through to the
      next bioreactor, after the cells have been trypsinized and detached from
      microcarriers. The operating feasibility of the cell-detaching reactor was tested
      with anchorage-dependent recombinant Chinese hamster ovary (rCHO) and African
      green monkey kidney (Vero) cells. rCHO and Vero cells were first cultured in a
      small microcarrier bioreactor, and then inoculated via the cell-detaching reactor
      into either a packed-bed bioreactor (for rCHO cells) or a larger microcarrier
      bioreactor (for Vero cells). For rCHO cells, the cell density reached 1.3 x 10(7)
      cells/ml in the perfusion culture, and Vero cells reached 1.3 x 10(6) cells/ml in
      the batch culture.

PMID- 17216538
TI  - Stimulation of saponin production in Panax ginseng hairy roots by two
      oligosaccharides from Paris polyphylla var. yunnanensis.
AB  - Two oligosaccharides, a heptasaccharide (HS) and an octasaccharide (OS), isolated
      from Paris polyphylla var. yunnanensis, stimulated the growth and saponin
      accumulation of Panax ginseng hairy roots at 5-30 mg l(-1). HS and OS at 30 mg l(
      1), fed separately to hairy root cultures at 10 days post-inoculation, increased
      the root biomass dry weight by more than 70% to approximately 20 g l(-1) from 13
      g l(-1) and the total saponin content of roots by more than 1-fold to
      approximately 3.5% from 1.6% (w/w). The results suggest that the two
      oligosaccharides may have plant growth-regulatory activity in plant tissue
      cultures.

PMID- 17216539
TI  - Degradation of polycyclic aromatic hydrocarbons in soil by a two-step sequential
      treatment.
AB  - The objectives of this work were to isolate the microorganisms responsible for a
      previously observed degradation of polycyclic aromatic hydrocarbons (PAH) in soil
      and to test a method for cleaning a PAH-contaminated soil. An efficient PAH
      degrader was isolated from an agricultural soil and designated as Mycobacterium
      LP1. In liquid culture, it degraded phenanthrene (58%), pyrene (24%), anthracene
      (21%) and benzo(a)pyrene (10%) present in mixture (initial concentration 50
      microg ml(-1) each) and phenanthrene (92%) and pyrene (94%) as sole carbon
      sources after 14 days of incubation at 30 degrees C. In soil, Mycobacterium LP1
      mineralised (14)C-phenanthrene (45%) and (14)C-pyrene (65%) after 10 days. The
      good ability of this Mycobacterium was combined with the benzo(a)pyrene oxidation
      effect obtained by 1% w/w rapeseed oil in a sequential treatment of a PAH-spiked
      soil (total PAH concentration 200 mg kg(-1)). The first step was incubation with
      the bacterium for 12 days and the second step was the addition of the rapeseed
      oil after this time and a further incubation of 22 days. Phenanthrene (99%),
      pyrene (95%) and anthracene (99%) were mainly degraded in the first 12 days and a
      total of 85% of benzo(a)pyrene was transformed during the whole process. The
      feasibility of the method is discussed.

PMID- 17216540
TI  - Retrieving the ars moriendi tradition.
AB  - North Atlantic culture lacks a commonly shared view on dying well that helps the
      dying, their social environment and caregivers to determine their place and role,
      interpret death and deal with the process of ethical deliberation. What is
      lacking nowadays, however, has been part of Western culture in medieval times and
      was known as the ars moriendi (art of dying well) tradition. In this paper an
      updated version of this tradition is presented that meets the demands of present
      day secularized and multiform society. Five themes are central to the new art of
      dying: autonomy and the self, pain control and medical intervention, attachment
      and relations, life balance and guilt, death and afterlife. The importance of
      retrieving the ancient ars moriendi outreaches the boundaries of palliative
      medicine, since it deals with issues that play a central role in every context of
      medical intervention and treatment.

PMID- 17216542
TI  - No association between polymorphism in the vascular endothelial growth factor
      gene at position -460 and sporadic prostate cancer in the Turkish population.
AB  - The development and progression of prostate cancer (PCa) has biologically and
      genetically remained a mystery. A man's risk of developing PCa is influenced by
      both genetic and environmental factors. Angiogenic cytokines like vascular
      endothelial growth factor (VEGF) play a pivotal role in tumor angiogenesis.
      Single nucleotide polymorphisms in angiogenesis-dependent genes affect the
      sensibility of cancer development and progression. Therefore, we hypothesized a
      potential association between DNA sequence variations in VEGF -460 gene region
      and sporadic PCa patients in the Turkish population. 133 sporadic PCa patients
      and 157 healthy controls were studied. Genotypes were determined by polymerase
      chain reaction (PCR) and restriction fragment length polymorphism (RFLP)
      analysis. The distribution of genotype and allele frequencies of the polymorphism
      did not yield a statistically significant difference between patients and
      controls (P>0.05). Furthermore, classification of patients by tumor-lymph nodes
      metastasis (TNM), Gleason Scores (GS) and serum prostate-specific antigen (PSA)
      levels did not show significant differences among the VEGF -460 C>T genotypes
      (P>0.05). This is the first demonstration showing that the VEGF -460 C>T
      polymorphism in men is not associated with sporadic PCa in the Turkish
      population.

PMID- 17216543
TI  - The interval between cancer diagnosis among mothers and offspring in a population
      based cohort.
AB  - BACKGROUND: Familial cancers may be due to shared genes or environment, or chance
      aggregation. We explored the possibility that ascertainment bias influences
      cancer detection in families, bearing upon the time interval between diagnosis of
      affected mothers and offspring. METHODS: The Jerusalem Perinatal Study (JPS)
      comprises all mothers (n = 39,734) from Western Jerusalem who gave birth 1964 
      1976 and their offspring (n = 88,829). After linking identification numbers with
      Israel's Cancer Registry we measured the absolute time interval between initial
      cancer diagnoses in affected mother-offspring pairs. We tested the probability of
      obtaining intervals as short as those observed by chance alone, using a
      permutation test on the median interval. RESULTS: By June 2003 cancer had
      developed in 105 mother-offspring pairs within the cohort. Common sites among
      mothers were breast (47%), colorectal (9%), non-Hodgkin lymphoma (NHL) (8%) and
      cervix (7%), while for offspring in affected pairs common cancers were leukemia
      (12.4%), thyroid (13.3%), NHL (10.5%), breast (10.5%) and melanoma (7.6%). The
      median interval between diagnoses was 5.9 years, but for 33% of affected pairs
      the interval was < or =3 years. The probability of this occurring by chance alone
      was 0.03. This held true whether the offspring's or mother's diagnosis was first
      (P < 0.01). CONCLUSIONS: In a population-based cohort followed for three decades,
      the absolute interval between the diagnosis of cancer in mothers and their
      offspring is shorter than expected by chance. Explanations include shared
      environmental exposures or the possibility that cancer ascertainment in one pair
      member affects health behaviors in the other resulting in early diagnosis. The
      latter may bias the estimation of anticipation and survival in familial cancers.

PMID- 17216544
TI  - Identification of a founder BRCA2 mutation in Sardinian breast cancer families.
AB  - The population of Sardinia is characterized by a relatively low level of genetic
      heterogeneity: therefore 'founder mutations' can be expected to be found. We
      analysed 17 probands from families with high incidence of breast cancer or breast
      and ovarian cancer by sequencing the full-length coding regions of BRCA1 and
      BRCA2 genes. A novel BRCA2 frame-shift mutation, 3951del3insAT, which produces a
      protein truncated at codon 1258, was observed in six patients with BC from the
      same village. The mutation was not found in unaffected females (matched on basis
      of ethnicity and age) with no family history of cancer. Haplotype analysis
      strongly suggests that all affected persons had a common ancestor. The
      identification of this clinically significant founder mutation may facilitate
      screening/testing for inherited risk of breast cancer.

PMID- 17216545
TI  - A wheat genomic DNA fragment reduces pollen transmission of maize transgenes by
      reducing pollen viability.
AB  - A genomic DNA fragment from wheat carrying the Glu-1Dx5 gene has been shown to
      exhibit reduced pollen transmission in transgenic maize. To localize the region
      of the DNA fragment responsible for this reduced pollen transmission, we produced
      transgenic maize plants in which the wheat genomic DNA proximal to the 1Dx5
      coding sequence was replaced with the maize 27 kDa gamma-zein promoter. Like the
      wheat promoter-driven Glu-1Dx5 transgene, this zein promoter-driven transgene
      functioned to produce 1Dx5 in maize endosperm. However, with the zein promoter
      driven transgene, pollen transmission of the transgene loci was normal in most
      self- and cross-pollinations. We concluded that the wheat genomic DNA proximal to
      the wheat 1Dx5 coding sequence was required for reduced pollen transmission of
      the transgene in maize. In two of four transformation events of the wheat
      promoter-driven construct examined, pollen exhibited two morphological classes.
      In one class, pollen was normal in morphology and displayed average viability,
      and in the second, pollen was reduced in size and did not germinate on artificial
      media. DNA from the transgene was detectable in mature pollen from plants with
      reduced pollen transmission of transgene loci. To explain these observations, we
      hypothesize that elements within the transgene construct interfere with pollen
      development. We demonstrated that the wheat genomic DNA fragment can be used to
      control pollen transmission of an herbicide resistance transgene genetically
      linked to it. The wheat genomic DNA fragment may contain elements that are useful
      for controlling pollen transmission of transgene loci in commercial maize grain
      and seed production.

PMID- 17216546
TI  - Stability of Potato virus X expression vectors is related to insert size:
      implications for replication models and risk assessment.
AB  - We investigated the stability of expression constructs based on Potato virus X
      (PVX) as a function of insert length. Five different inserts ranging in length
      from 261 to 1,758 bp (human proinsulin, murine interleukin-10, HIV-1 nef, petunia
      expansin-1 and human gad65) were expressed using a PVX vector in Nicotiana
      benthamiana plants for three sequential passages. Using a competitive RT-PCR
      approach we demonstrated that insert-deletion could occur in the first infection
      cycle for all inserts, but that this was much more likely to be the case for
      longer ones. This suggested a negative correlation between insert length and
      vector stability. Sequence analysis of the deleted constructs suggested that
      recombination usually occurred at sites close to the duplicated sub-genomic
      promoter, but in a smaller number of cases the foreign gene itself was probably
      involved, resulting in partially deleted constructs containing transgene
      fragments. The implications of these results in the context of recombinant
      protein expression and its risks are discussed.

PMID- 17216548
TI  - Preclinical cardio-safety assessment of torsadogenic risk and alternative methods
      to animal experimentation: the inseparable twins.
AB  - The last decade has been marked by the withdrawal from the market of several
      medicines whose use in patients has been associated with the development of
      torsade de pointes (TdP), a potentially life-threatening polymorphic tachycardia.
      In a few cases, TdP can degenerate into ventricular fibrillation and lead to
      sudden death, thus constituting a real problem of public health. The recently
      finalized ICH S7B guideline defines the prolongation of the QT interval on the
      electrocardiogram as the best biomarker for predicting the torsadogenic risk of a
      given compound. However, a growing body of evidence suggests that drugs'
      torsadogenic potential may not necessarily be proportional to their ability to
      prolong the QT interval. It is a dynamic combination of multiple predisposing
      factors and components rather than a single particular event that can trigger
      this particular tachycardia. Following recommendations of the guideline,
      pharmaceutical companies have intensively implemented methodologies to assess the
      possible risk of QT prolongation and TdP in humans. The main problem in cardiac
      safety pharmacology is how best to combine the capabilities of different
      methodologies with their strengths and limitations in order to detect the
      potential of one molecular entity to induce a lethal arrhythmia of very low
      clinical incidence. This publication will review the current methodologies,
      focusing on the alternative methods to animal experimentation, including an
      overview of cardiac modeling.

PMID- 17216547
TI  - Risk of breast cancer associated with short-term use of oral contraceptives.
AB  - OBJECTIVE: To estimate breast cancer risk associated with short-term (<6 months)
      oral contraceptive use, and explore variation in estimates by use characteristics
      and medical, menstrual, and reproductive history. METHODS: We analyzed data from
      the Women's Contraceptive and Reproductive Experiences Study. Case subjects were
      white women and black women, 35-64 years old, diagnosed with invasive breast
      cancer in July 1994-April 1998. Control subjects identified by random-digit
      dialing were matched to case subjects by age, race, and study site. Conditional
      logistic regression was used to estimate odds ratios (ORs) and 95% confidence
      intervals (CIs). RESULTS: Overall, short-term oral contraceptive use was not
      associated with breast cancer risk (OR = 1.0; 95% CI = 0.8-1.1). However,
      significant interaction between short-term use and menopausal status led to an
      observed increased breast cancer risk in pre-menopausal women (OR = 1.3; 95% CI =
      1.0-1.7) and a reduced risk in post-menopausal women (OR = 0.8; 95% CI = 0.6-1.0)
      associated with short-term use. The association was more pronounced in women with
      non-contraceptive reasons for use and underlying risk factors for breast cancer.
      CONCLUSIONS: These associations may result from underlying characteristics of
      users or unmeasured factors influencing duration of use and breast cancer risk.

PMID- 17216550
TI  - Molecular phylogeography of two sibling species of Eurema butterflies.
AB  - The common yellow butterfly Eurema hecabe is widely distributed in East Asia, and
      is one of the most burdensome species for taxonomists due to the numerous
      geographic and seasonal wing colour patterns. Moreover, within this species,
      individuals with a yellow wing fringe that occur in temperate regions of Japan (Y
      type) proved to be biologically different from others that occur widely in
      subtropical regions of Japan and all over East Asia (B type). To unveil the
      genetic variation within and between the two types, a total of 50 butterflies
      collected at 18 geographic localities in East Asia were examined for nucleotide
      sequence variation of three mitochondrial regions: cytochrome c oxidase subunit I
      (COI), cytochrome c oxidase subunit III (COIII) and NADH dehydrogenase subunit 5
      (ND5). In addition, they were also examined for infection status with the
      endosymbiotic bacteria Wolbachia. The three mitochondrial sequences consistently
      showed that (i) Y type and B type were highly divergent, (ii) nucleotide
      variation within B type was very small although sampled from a geographically
      wide range, and (iii) a weak association existed between mitochondrial DNA
      haplotypes and Wolbachia infection status.

PMID- 17216549
TI  - Health-related quality of life as a predictor of mortality among community
      dwelling older persons.
AB  - Health-related quality of life (HRQOL) measures predict cause-specific mortality,
      but few studies have explored whether generic self-reported HRQOL measures are
      independently associated with mortality in community-dwelling older persons. We
      postulated that a general measure of HRQOL, the short form 36-item questionnaire
      (SF-36), would be independently predictive of mortality among community-dwelling
      older persons. To evaluate this hypothesis, we followed a fixed cohort of 4,424
      community-dwelling older persons recruited from a 2000 population-based survey in
      Taiwan until 2003 and investigated whether HRQOL was predictive of 3-year
      mortality, even after adjusting for traditional clinical risk variables. The data
      were collected via a door-to-door survey, and interviewers collected information
      on the subjects' demographics, medical history, utilization of health services,
      functional ability, falls, and self-reported physical and mental symptoms. Of the
      6053 eligible subjects, 4,424 residents agreed to participate in the baseline
      survey and were contacted in 2003. During the 3-year period, the 3-year
      cumulative mortality rate for the study population was 5%. Mortality was
      significantly higher among males (5.57% vs. 4.27%, p = 0.049), and cumulative
      mortality increased with age (chi (2)-test for trend; chi (2) = 7.734, p =
      0.001). For all scales except bodily pain, there was a significant relationship
      between a 10-point lower baseline score and mortality. Our primary multivariate
      risk model, which included two summary measures of HRQOL and significant clinical
      variables, demonstrated that a 10-point decrease in either the baseline Physical
      Component Summary (PCS) score or the baseline Mental Component Summary (MCS)
      score was associated with higher mortality (PCS: RR: 1.60, 95% CI: 1.39-1.83; p <
      0.001; MCS: RR: 1.16, 95% CI: 1.01-1.34; p = 0.036). The findings suggested that
      low baseline PCS and MCS scores were important independent risk factors for 3
      year mortality among community-dwelling older persons, even after adjusting for
      other risk factors.

PMID- 17216551
TI  - The gynogenetic reproduction of diploid and triploid hybrid spined loaches
      (Cobitis: Teleostei), and their ability to establish successful clonal lineages-
      on the evolution of polyploidy in asexual vertebrates.
AB  - Polyploidisation is assumed to have played a significant role in the evolution of
      hybrid asexual lineages. The virtual absence of natural asexual systems in which
      more than a single ploidy level successfully establishes successful independent
      clonal lineages is generally explained by the strong effects of polyploidisation
      on fitness. Experimental crosses were made between diploid and triploid asexual
      Cobitis elongatoides x C. taenia hybrids (female) and both parental spined loach
      species (male). Genotyping of the progeny using allozymes and multilocus DNA
      fingerprinting, along with flow cytometric measurement of ploidy level,
      demonstrated the occurrence of gynogenetic reproduction in both female biotypes.
      The incorporation of the sperm genome occurred in some progeny, giving rise to a
      higher ploidy level, but the rate of polyploidisation differed significantly
      between the diploid and triploid females. These outcomes are consistent with the
      existence of developmental constraints on tetraploidy, which determine the rarity
      of tetraploids in natural populations. No cases of ploidy level reduction were
      observed. Since diploid and triploid hybrid populations occur where the lack of
      potential progenitor excludes the possibility of de novo origin, it is probable
      that both diploid and triploid females can establish successful clonal lineages.
      Spined loaches represent a unique example, among asexual vertebrates, where more
      than one ploidy level can establish persistent clonal lineages, which are
      reproductively independent of one another.

PMID- 17216552
TI  - Sexual function in women after rectocele repair with acellular porcine dermis
      graft vs site-specific rectovaginal fascia repair.
AB  - The objective of the study was to compare preoperative and postoperative sexual
      function between women undergoing rectocele repair with porcine dermis graft and
      women undergoing site-specific repair of rectovaginal fascia. A standardized,
      validated questionnaire (Pelvic Organ Prolapse/Urinary Incontinence Sexual
      Function Questionnaire [PISQ]) was used to collect preoperative sexual function
      data from 100 patients with rectocele pelvic organ prolapse quantification stage
      2 or greater. Fifty women underwent rectocele repair utilizing porcine dermis
      graft (group 1) and 50 women underwent a site-specific repair of the rectovaginal
      fascia (group 2). The same questionnaire was administered to all subjects 6
      months after surgery. The two groups were similar in age, race, parity, prior
      hysterectomy, and postmenopausal hormone use. Preoperative sexual function scores
      were similar in the two groups (group 1 81.4+/-7.3 and group 2: 83.6+/-8.2,
      p=1.0). Six months after surgery, PISQ scores in group 1 significantly increased
      (score increase 19.9+/-2.2, p=0.01). The mean increase in PISQ scores for group 2
      was 6.9+/-3.1 (p=0.08). When compared with group 2, subjects undergoing rectocele
      repair with porcine dermis graft scored significantly higher on the PISQ 6 months
      after surgery (group 1 101.3+/-6.4 and group 2 89.7+/-7.1, p=0.01). We conclude
      that rectocele repair using porcine dermis graft is associated with improved
      sexual functioning when compared with site-specific rectovaginal fascia repair.

PMID- 17216553
TI  - Prevalence and impact of nocturia in a urogynecologic population.
AB  - To determine the prevalence of nocturia and associated bother among patients
      presenting to a tertiary urogynecology clinic and to describe patient
      characteristics related to nocturic frequency and associated bother. Chart review
      of sequential new patients presenting to our clinic between June 2004 and May
      2005. We recorded patients' response to a question about their frequency of
      nocturia, the level of associated bother, demographic data, history of chronic
      medical illness and clinical urogynecologic diagnosis. Seven hundred sixty
      patients were of mean age 56 (19-95) years. Eighty-seven percent of patients
      voided at least once nightly, and 60% usually voided at least twice nightly.
      Forty one percent of patients reported bother >or=5/10 from nocturia. High bother
      rating was associated with increasing number of nocturic episodes (p < 0.0005)
      and mixed incontinence (p = 0.012). Nocturia is common and bothersome to women
      presenting for urogynecologic care. Concomitant mixed incontinence significantly
      increases bother arising from nocturia.

PMID- 17216554
TI  - Differences of bone mass and bone structure in osteopenic rat models caused by
      spinal cord injury and ovariectomy.
AB  - Both spinal cord injury and ovariectomy can result in ostepenia in rats. SCI
      induces more deterioration of cortical geometric structure and trabecular
      microstructure in the proximal tibial metaphysis than OVX. The proximal tibial
      metaphysis microstructure significantly correlates with its biomechanical
      properties. INTRODUCTION: The purpose of the present study was to compare the
      effects of spinal cord injury (SCI) and ovariectomy (OVX) on bone gain in young
      female rats. METHODS: Thirty young female Sprague-Dawley rats were randomized
      into three groups: age-matched intact control (CON), OVX and SCI. The tibiae were
      assessed for DXA and micro-CT analysis, biomechanical testing, the upper tibial
      epiphyseal plate height, and blood samples for biochemical analysis. RESULTS: SCI
      rats showed lower aBMD in the proximal tibiae as compared with OVX rats. Cortical
      geometric structural parameters of the tibial midshaft in SCI rats were
      significantly lower than OVX rats. SCI or OVX induced significant changes in all
      trabecular microstructural parameters in the proximal tibial metaphysis. The
      trabecular separation (Tb.Sp) and structure mode index (SMI) in SCI rats were
      significantly higher than in OVX rats. BV/TV explained 84% of the variation of
      ultimate load of the proximal tibial metaphysis. There was no difference of the
      upper tibial epiphyseal plate height between SCI and OVX rats. Serum NTX level in
      SCI rats was significantly higher than in OVX rats. CONCLUSIONS: SCI induces more
      deterioration of cortical bone geometric structure and trabecular microstructure
      in the proximal tibial metaphysis than OVX.

PMID- 17216556
TI  - Remembrance of things past.

PMID- 17216557
TI  - Hepatitis and rhabdomyolysis in a patient with hormone refractory prostate cancer
      on ketoconazole and concurrent lovastatin therapy.

PMID- 17216555
TI  - Promoter hypermethylation profile of cell cycle regulator genes in pituitary
      adenomas.
AB  - Aberrant hypermethylation of CpG islands in the promoter region plays a causal
      role in the inactivation of various key genes involved in the cell cycle
      regulatory cascade, which could result in a loss of cell cycle control. The aim
      of the present study was to examine in more detail the prevalence and role of the
      promoter methylation of genes with a proven involvement in the cell cycle
      regulation of pituitary adenomas, since their tumorigenesis has not yet been
      clearly defined. We profiled the CpG island methylation status of a series of
      well-characterized cell cycle regulation genes: the RB1, p14(ARF), p15(INK4b),
      p16(INK4a), p21(Waf1/Cip1), p27(Kip1), and p73 genes, in 34 pituitary adenomas as
      determined by a methylation-specific polymerase chain reaction assay. Promoter
      hypermethylation of the RB1, p14(ARF), p15(INK4b), p16(INK4a), p21(Waf1/Cip1),
      p27(Kip1), and p73 genes was detected in 12 (35%), 2 (6%), 11 (32%), 20 (59%), 1
      (3%), 0 (0%), and 4 (12%) of the adenomas, respectively. In total, 88% (30 of 34)
      of the adenomas displayed methylation of at least one of such cell cycle
      regulatory genes, especially methylation of the member genes of the RB1 pathway
      (29 of 34; 85%). Promoter hypermethylation of p15(INK4b) coincided with RB1
      and/or p16(INK4a) methylation, whereas RB1 and p16(INK4a) methylations tended to
      be mutually exclusive (p = 0.0048). Furthermore, promoter hypermethylations of
      p14(ARF), p21(Waf1/Cip1), and p73 (not belonging to the member genes of the RB1
      pathway) were also coincident with RB1 and/or p16(INK4a) methylation except in
      one p73 methylated case. In contrast, none of the clinicopathological features,
      including the cell proliferation index, was significantly correlated with any
      particular methylation status. Our results suggested that aberrant
      hypermethylation of the key cell cycle regulatory genes occurs at a relatively
      high frequency in pituitary adenomas, especially in RB1 pathway genes with
      promoter hypermethylation of the p16(INK4a) gene being the most common
      deregulation. We further obtained evidence to indicate that RB1 and p16(INK4a)
      methylations tended to be mutually exclusive, but did occasionally coincide with
      other cell cycle regulation gene methylations.

PMID- 17216558
TI  - "Accept me, or else...": disputed overestimation of social competence predicts
      increases in proactive aggression.
AB  - It has been proposed that aggressive behavior may result from unrealistically
      positive self-evaluations that are disputed by others (Baumeister, Smart, &
      Boden, 1996). The present three studies tested this proposition concurrently and
      longitudinally for the domain of self-perceived social competence (SPSC) in 3-6th
      grade children on two continents. Each study tested whether aggressive behavior
      is related to general overestimation of SPSC compared to competence as perceived
      by peers, or to disputed overestimation, that is, overestimation disputed through
      rejection by peers. Specificity of relations with reactively or proactively
      aggressive behavior patterns was assessed and the predictive value of
      overestimation to the development of these types of aggressive behavior was
      investigated. Concurrently, disputed overestimation explained more variance in
      aggressive behavior than general overestimation, and was uniquely related to
      proactive aggression. Longitudinally, disputed overestimation also uniquely
      predicted changes in proactive, not reactive aggression.

PMID- 17216559
TI  - Social skills training for adolescents with Asperger syndrome and high
      functioning autism.
AB  - The effectiveness of a social skills training group for adolescents with Asperger
      syndrome and high-functioning autism (AS/HFA) was evaluated. Parents of six
      groups of adolescents (n = 46, 61% male, mean age 14.6) completed questionnaires
      immediately before and after the 12-week group. Parents and adolescents were
      surveyed regarding their experience with the group. Significant pre- to post
      treatment gains were found on measures of both social competence and problem
      behaviors associated with AS/HFA. Effect sizes ranged from .34 to .72.
      Adolescents reported more perceived skill improvements than did parents. Parent
      reported improvement suggests that social skills learned in group sessions
      generalize to settings outside the treatment group. Larger, controlled studies of
      social skills training groups would be valuable.

PMID- 17216560
TI  - Early social, imitation, play, and language abilities of young non-autistic
      siblings of children with autism.
AB  - Studies are needed to better understand the broad autism phenotype in young
      siblings of children with autism. Cognitive, adaptive, social, imitation, play,
      and language abilities were examined in 42 non-autistic siblings and 20 toddlers
      with no family history of autism, ages 18-27 months. Siblings, as a group, were
      below average in expressive language and composite IQ, had lower mean receptive
      language, adaptive behavior, and social communication skills, and used fewer
      words, distal gestures, and responsive social smiles than comparison children.
      Additionally, parents reported social impairments in siblings by 13 months of
      age. These results suggest that the development of young non-autistic siblings is
      affected at an early age and, thus, should be closely monitored, with appropriate
      interventions implemented as needed.

PMID- 17216561
TI  - Trends in special education code assignment for autism: implications for
      prevalence estimates.
AB  - There is considerable controversy over reasons for observed increases in the
      prevalence of autism spectrum disorders. We examined trends in British Columbia
      education database coding of children with autism from 1996 to 2004. There was a
      significant linear increase in autism prevalence. The proportion of children
      identified by age 6 increased significantly from 1996 to 1999. When we calculated
      prevalence assuming onset prior to age 3, previously unidentified cases,
      particularly among girls in 1996 and 1997, accounted for substantial increases in
      estimated prevalence. The magnitude of under-identification decreased from 1996
      to 2000, and rose slightly in 2001. Analyses of prevalence trends must take into
      account effects of earlier age at identification and inclusion of previously
      undetected cases on prevalence estimates.

PMID- 17216562
TI  - Effect of apoptosis and reactive oxygen species production in human granulosa
      cells on oocyte fertilization and blastocyst development.
AB  - PURPOSE: The aim was to establish the impact of human granulosa cell apoptosis
      and reactive oxygen species (ROS) production on fertilization competence of the
      oocyte, embryo developmental stage and implantation rate. METHODS: Thirty women
      undergoing IVF-ET for tubal factor infertility were included; GnRH antagonists
      and gonadotrophins were used for ovarian stimulation. Granulosa cells were
      isolated from each aspirated follicle using gradient centrifugation. Apoptosis
      was studied by flow cytometry using annexin V and propidium iodide. ROS
      production was studied with hydroethidine staining and analyzed by flow
      cytometry. RESULTS: There were no differences in characteristics of granulosa
      cells between the follicles with fertilized and non-fertilized oocytes. The
      analyzed characteristics of granulosa cells in corresponding follicles had no
      effect on embryo developmental stage on day 5. The percentage of ROS producing
      granulosa cells was lower in the follicles giving rise to blastocysts that
      resulted in implantation compared to those that did not (39.9% versus 69.9%, P =
      0.031). CONCLUSIONS: Apoptosis and ROS production in granulosa cells have no
      significant impact on fertilization and do not correlate with the development of
      blastocysts. An increased percentage of ROS producing granulosa cells results in
      fewer oocytes retrieved and diminishes implantation rate.

PMID- 17216563
TI  - The pre-cycle blind mock embryo transfer is an inaccurate predictor of
      anticipated embryo transfer depth.
AB  - PURPOSE: To assess if the uterine cavity depth measured by a blind pre-cycle mock
      transfer changes after gonadotropin stimulation. METHODS: This is a retrospective
      cohort study at an academic IVF program involving 128 infertility patients. The
      main outcome measures were uterine cavity depth measured at the blind pre
      stimulation mock transfer and the ultrasound-guided embryo transfer. RESULTS: A
      >or= 1 cm increase in uterine cavity depth was found in 57.9% of the patients.
      The mean pre-cycle blind mock transfer uterine depth significantly differed from
      the mean uterine depth measured at embryo transfer. Based on the mock transfer,
      the anticipated embryo transfer depth was significantly less than the actual
      ultrasound-guided embryo transfer depth. CONCLUSION: Uterine depth significantly
      differed between the blind pre-cycle mock transfer measurement and the ultrasound
      guided embryo transfer measurement. The mock transfer may predict a difficult
      embryo transfer but it is an inaccurate predictor of the final embryo transfer
      depth.

PMID- 17216564
TI  - Discordance among blastomeres renders preimplantation genetic diagnosis for
      aneuploidy ineffective.
AB  - PURPOSE: To investigate the contribution of discordance among blastomeres from
      the same embryo in the interpretation of blastomeres biopsied from day 3 embryos.
      METHODS: 228 IVF embryos had two blastomeres removed and fluorescent in situ
      hybridization (FISH) was used to detect aneuploidy of chromosomes 13, 15, 16, 18,
      21, 22, X and Y. Of the 228 embryos, 102 had complete FISH results for both
      blastomeres. RESULTS: When the 2 blastomeres of 102 embryos with successful FISH
      results were compared, 26 (25.5%) were concordant for all 8 chromosomes and 76
      (74.5%) were discordant for one or more chromosomes. Among the 102 embryos, 12
      (12%) were disomy in both blastomeres and 37 (36%) were disomic in all 8
      chromosomes in one of the two blastomeres. CONCLUSION: Discordance among
      blastomeres from the same embryo appears to present a significant problem in
      interpreting results of embryos biopsied on day 3 and analyzed by FISH especially
      when most PGD's are done on single blastomeres.

PMID- 17216566
TI  - The expression of retinoic acid receptors in lymph nodes of young children and
      the effect of all-trans-retinoic acid on the B cells from lymph nodes.
AB  - To elucidate the mechanism of vitamin A enhancing the production of antibody, we
      examined the expression and distribution of retinoic acid receptors mRNA in lymph
      nodes of young children ( < or = 5 years of age), and investigated the affection
      of all-trans-retinoic acid on the maturation and activation of the B cells
      isolated from the lymph nodes and cultured in vitro. Twenty-four normal lymph
      nodes were collected. By in situ hybridization, we found that all six retinoic
      acid receptor genes expressed and distributed widely in the lymph nodes, and the
      levels of mRNA for retinoic acid receptor genes (detected by RT-fluorescent
      quantitative PCR) were increased with the development of children. In vitro
      culture, all-trans retinoic acid promoted the maturation and activation of the B
      cells from the lymph nodes. Thus, promotion on B cells in lymph node may be the
      important mechanism of vitamin A reinforcing the humoral immunity in young
      children.

PMID- 17216567
TI  - Comparative kinetic effects of Mn (II), Mg (II) and the ATP/ADP ratio on
      phosphoenolpyruvate carboxykinases from Anaerobiospirillum succiniciproducens and
      Saccharomyces cerevisiae.
AB  - The kinetic affinity for CO(2) of phosphoenolpyruvate PEP(5) carboxykinase from
      Anaerobiospirillum succiniciproducens, an obligate anaerobe which PEP
      carboxykinase catalyzes the carboxylation of PEP in one of the final steps of
      succinate production from glucose, is compared with that of the PEP carboxykinase
      from Saccharomyces cerevisiae, which catalyzes the decarboxylation of
      oxaloacetate in one of the first steps in the biosynthesis of glucose. For the A.
      succiniciproducens enzyme, at physiological concentrations of Mn(2+) and Mg(2+),
      the affinity for CO(2) increases as the ATP/ADP ratio is increased in the assay
      medium, while the opposite effect is seen for the S. cerevisiae enzyme. The
      results show that a high ATP/ADP ratio favors CO(2) fixation by the PEP
      carboxykinase from A. succiniciproducens but not for the S. cerevisiae enzyme.
      These findings are in agreement with the proposed physiological roles of S.
      cerevisiae and A. succiniciproducens PEP carboxykinases, and expand recent
      observations performed with the enzyme isolated from Panicum maximum (Chen et al.
      (2002) Plant Physiology 128: 160-164).

PMID- 17216565
TI  - Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases,
      and in the prevention of allograft rejection: a 25-year personal odyssey.
AB  - Twenty-five years ago, we reported the production of the monoclonal antibody,
      anti-Tac that identifies the IL-2 receptor alpha subunit and blocks the
      interaction of IL-2 with this growth factor receptor. In 1997, daclizumab
      (Zenapax), the humanized form of this antibody, was approved by the FDA for use
      in the prevention of renal allograft rejection. In addition, we demonstrated that
      daclizumab is of value in the treatment of patients with noninfectious uveitis,
      multiple sclerosis, and the neurological disease human T-cell lymphotropic virus
      I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Others
      demonstrated therapeutic efficacy with daclizumab in patients with pure red cell
      aplasia, aplastic anemia, and psoriasis. Thus, translation of basic insights
      concerning the IL-2/IL-2 receptor system obtained using the monoclonal antibody
      daclizumab provided a useful strategy for the prevention of organ allograft
      rejection and the treatment of patients with select autoimmune diseases or T-cell
      leukemia/lymphoma.

PMID- 17216568
TI  - Polymorphism analysis of Epstein-Barr virus isolates of nasopharyngeal carcinoma
      biopsies from Tunisian patients.
AB  - Many studies suggest that the focal distribution of nasopharyngeal carcinoma
      (NPC) may be influenced not only by host genetics, diet and environments but also
      by interplay with Epstein-Barr virus (EBV) genetics. Specific EBV gene variants
      (the A and C types, the BamHI f configuration, a C terminal 30 bp deletion and a
      N terminal loss of an XhoI site in the BNLF1 gene) have been explored in high
      incidence areas in southern Asian NPC patients. In contrast, in Tunisia where NPC
      represents the most frequent type of Head and Neck cancer the distribution of
      these polymorphisms remains poorly investigated. In order to characterize the
      epidemiology of EBV variants in Tunisian NPC patients, we have investigated the A
      or B type of the EBV nuclear antigen (EBNA)2 gene, the C or D type of the BamHI
      W1/I1 region, the F/f variants of the BamHI F region and the presence or the
      absence of the XhoI site, 30 bp deletion and Taq1 site in the BNLF1 gene in 47
      NPC biopsies, 12 being younger than 30 and 35 older than 30. Our results show a
      unique genetic profile of the tumor EBV strains regarding the A and D types, the
      prototype F and retention of the XhoI restriction site in the N terminal region
      of BNLF1 gene. With regard to the C terminal region of this gene, four genetic
      profiles were detected: (1) the occurrence of the 30 bp deletion in association
      with the Taq1 site in 39 cases (83%), (2) the presence of the Taq1 site by itself
      in 5 cases, (3) the occurrence of the 30 bp deletion by itself in 2 cases and (4)
      the occurrence of a new deletion of 81 bp covering the 30 bp deletion in
      association with the Taq1 site in one case. With the exception of the 81 bp
      deletion, which has not been previously described in the literature, the
      summarized results have shown the same genetic profile in Tunisian NPC tumor
      isolates as tumor isolates from other North African and Mediterranean countries.
      Hence, the observed EBV polymorphisms are not fully specific of to the Tunisian
      NPCs. Nevertheless, the notion of a divergence between North African and Asian
      tumor EBV isolates is reinforced by this study.

PMID- 17216569
TI  - Depressive symptoms among firefighters and related factors after the response to
      Hurricane Katrina.
AB  - The National Institute for Occupational Safety and Health conducted an evaluation
      regarding physical and psychological health symptoms among New Orleans
      firefighters 13 weeks after Hurricane Katrina struck the U.S. Gulf Coast on
      August 29, 2005. This report examines associations between depressive symptoms
      and concurrent comorbidity. Depressive symptoms were twice as likely among those
      with either lower respiratory symptoms or skin rash. Firefighters housed with
      their families were less likely to report depressive symptoms compared to those
      not living with their families. Perceived low supervisor support was associated
      with depressive symptoms, whereas participating in group counseling was not. The
      results underscore the need for the incorporation of physical and psychological
      health follow-up of emergency responders after natural disasters to better
      understand, monitor, and treat their health conditions.

PMID- 17216570
TI  - The Puerto Rico-New York airbridge for drug users: description and relationship
      to HIV risk behaviors.
AB  - This study examined mobility on the airbridge between New York (NY) and Puerto
      Rico (PR) for Puerto Rican drug users and its relationship to HIV risk. Over
      1,200 Puerto Rican injection drug users (IDUs) and crack smokers were recruited
      by outreach workers in NY and PR; interview data included questions on mobility
      (lifetime residences and recent trips). Two-thirds of the NY sample had lived in
      PR; one-quarter of the PR sample had lived in NY; the most commonly sited reasons
      for moving were family-related. Fewer than 10% had visited the other location in
      the prior 3 years. Variables related to risk were number of moves, recent travel,
      and having used drugs in PR (all with p < 0.05). Implications included the need
      to enhance risk reduction efforts for IDUs in PR and address sexual risk among
      mobile drug users.

PMID- 17216572
TI  - Co-located substance use treatment and HIV prevention and primary care services,
      New York State, 1990-2002: a model for effective service delivery to a high-risk
      population.
AB  - The New York State Department of Health (NYSDOH) AIDS Institute (AI) began an
      initiative in 1990 in collaboration with the Office of Alcoholism and Substance
      Abuse Services (OASAS) to colocate HIV prevention and clinical services at drug
      treatment clinics. In 1990, the initiative began funding drug treatment programs
      to provide HIV counseling, testing, and prevention services. HIV primary care was
      added the following year. Program implementation and development are described.
      An analysis is included of HIV counseling and testing data for the period 1990
      2002 and quality of care data for five standardized quality measures with
      comparisons to data from other clinical settings. In the first 13 years of the
      initiative 168,340 HIV-antibody tests were conducted including 52,562 tests of
      injection drug users (IDUs) identifying 14,612 HIV-infected persons; the
      seroprevalence was 8.68%. By the end of 2000, the HIV primary care caseload
      peaked at 3,815 patients. Quality of primary medical care services among
      participating drug treatment programs has consistently matched or exceeded that
      provided in more conventional health care settings such as the hospitals and
      community health centers that were used as a basis for comparison. Colocating HIV
      primary care within substance use treatment is an effective strategy for
      providing accessible high-quality HIV prevention and primary care services.

PMID- 17216571
TI  - The sociobiologic integrative model (SBIM): enhancing the integration of
      sociobehavioral, environmental, and biomolecular knowledge in urban health and
      disparities research.
AB  - Disentangling the myriad determinants of disease, within the context of urban
      health or health disparities, requires a transdisciplinary approach.
      Transdisciplinary approaches draw on concepts from multiple scientific
      disciplines to develop a novel, integrated perspective from which to conduct
      scientific investigation. Most historic and contemporary conceptual models of
      health were derived either from the sociobehavioral sciences or the biomolecular
      sciences. Those models deriving from the sociobehavioral sciences generally lack
      detail on involved biological mechanisms whereas those derived from the
      biomolecular sciences largely do not consider socioenvironmental determinants. As
      such, advances in transdisciplinary characterizations of health in complex
      systems like the urban environment or health disparities may be impeded. This
      paper suggests a sociobiologic organizing model that encourages a multilevel,
      integrative perspective in the study of urban health and health disparities.

PMID- 17216573
TI  - Elevated 13C urea breath test values females infected with Helicobacter pylori.
AB  - (13)C-urea breath test (UBT) for the diagnosis of Helicobacter pylori requires a
      high density and active bacteria and has the potential to provide a noninvasive
      index of bacterial growth. We describe the gender differences in delta over
      baseline (13)C-UBT values in 7373 patients (4531 females and 2842 males) who
      underwent (13)C-UBT test for the diagnosis of H. pylori infection. A
      significantly (P<.001) higher mean +/- SD excess delta (13)CO(2) excretion was
      recorded in females (24.7+/-17.4) compared to males (17.6+/-11.8) aged 10-80
      years. The age-adjusted difference between sexes was 7.1 (95% confidence
      interval, 6.4-7.9). Our analysis demonstrates quantitatively for the first time
      gender associated differences in H. pylori host interaction. This study suggests
      that infected females have a higher bacterial load and therefore may potentially
      infect their children at a higher degree than males.

PMID- 17216574
TI  - Protective effect of a novel rice extract against ethanol-induced gastric mucosal
      injury in rat.
AB  - The aim of this study was to investigate the protective action of rice extract on
      ethanol-induced mucosal damage in vivo and wound healing of epithelial cells in
      vitro. Also, the effect of rice extract on gastric mucosal prostaglandin E(2)
      level, HSP72 expression, gastric acid secretion, and contribution of vanilloid
      receptor-mediated action was studied. In addition, using cultured gastric mucosal
      cells (RGM-1), the effect of rice extract on cytoprotection and wound healing of
      epithelial cells was evaluated. Rice extract significantly reduced gastric
      mucosal damage produced by ethanol in vivo, and heat treatment (80 degrees C, 3
      min) of this agent did not alter its protective effect. Rice extract also
      protected RGM-1 from ethanol-induced damage in a dose-dependent manner. Rice
      extract accelerated wound healing of gastric epithelial cells. Our results
      demonstrate that rice extract could be an alternative ulcer treatment that
      provides cytoprotection and enhancement of wound healing not dependent on acid
      secretion, prostaglandin E(2) level, HSP72 expression, or vanilloid receptors.

PMID- 17216575
TI  - Impaired detoxication of hydrogen sulfide in ulcerative colitis?
AB  - Impaired butyrate oxidation and raised counts of sulfate-reducing bacteria in the
      colon of patients with ulcerative colitis (UC) indicate that the disease may be
      induced or aggravated by hydrogen sulfide toxicity. We aimed to examine enzymatic
      removal of H(2)S in erythrocytes and colonic mucosa from controls and patients
      with UC and Crohn's disease (CD). Rhodanese (RHOD) and thiol methyltransferase
      (TMT) activities were measured in rectal mucosa and erythrocytes, and plasma
      thiocyanate was determined. Four groups were analyzed: patients with UC, patients
      with CD, hospital controls (patients with dyspepsia or IBS), and a group of
      healthy volunteers. RHOD and TMT activity in rectal biopsies did not differ
      significantly between controls and patients with UC or CD (n=56). Control levels
      of RHOD were significantly higher in men than in women (212+/-25 and 132+/-14
      nmol/mg/min, respectively; P<0.01). In erythrocytes (n=128) RHOD activity was
      significantly higher in UC patients than in hospital or volunteer controls
      (1.15+/-0.12 compared with 0.88+/-0.12 and 0.66+/-0.02 nmol/mg/min; P<0.05 and
      P<0.02, respectively). TMT activity was also significantly higher in erythrocytes
      from UC patients and hospital controls than volunteer controls (2.02+/-0.13
      pmol/mg/min [P<0.001], 1.51+/-0.21 pmol/mg/min [P<0.05], and 1.17+/-0.18
      pmol/mg/min, respectively). We found no evidence of defective enzymic
      detoxication of sulfide by RHOD or TMT in patients with UC or CD.

PMID- 17216576
TI  - The use of the internet in data assimilation in rare diseases.
AB  - The incidence and prevalence of achalasia is 0.6/100,000 people per year and
      1/10,000, respectively. It is difficult then for one center to accumulate a large
      cohort of patients. One study (Gut 33:1011,1992) described the presenting
      symptoms in only 38 patients. To approach this problem differently, we used the
      internet to access a larger patient population. Using search engines at Google
      and Yahoo, Inc., we identified achalasia support groups. We examined the most
      populated support group (YSG) and assembled the exchanged messages into 4
      categories: support, symptoms, treatment, and diagnosis. Next, a survey modeled
      after a previous study (ibid) was composed and posted on a university-sponsored
      Web site for March 2003, advertised to YSG members, and then removed from the
      server. The results were entered into a database and analyzed. There were 6
      support groups identified; 1 was foreign. The most populated site was the Yahoo,
      Inc., group with 298 active members. We analyzed the 3,222 messages posted from
      October 6, 2002 through October 5, 2003. The message composition was as follows:
      67% support, 16% symptoms, 12% treatment, and 5% diagnosis. Of 298 Yahoo site
      members, we had 88 respondents to the survey from 9 countries. The data from 83
      were analyzed (5 were not completed). Respondents were 66 women (55%), 29 men
      (24%), and 5 non-gender-identified respondents. They ranged in age from 6 to 72
      years at time of diagnosis. In the 83 respondents, dysphagia symptoms were
      reported by 98%, regurgitation by 68%, chest pain by 81%, weight loss by 69%, and
      epigastric pain by 67%, similar to those reported in the study cited in Gut. The
      modalities used to evaluate these achalasia patients were as follows: 83% had
      monometry, 87% had radiography, and 89% had endoscopy. The mean time from symptom
      onset to diagnosis was 5 years. The treatments attempted on this population were
      balloon dilatation in 57%, botulinum toxin injection (Botox) in 8%, myotomy in
      12%, by lifestyle/diet modification in 12%, and other treatments in 11%. We
      believe that the Internet can provide physician-researchers with useful
      information about common and uncommon diseases on a global basis. The Internet
      allows patients to voice concerns that they may not freely express to their
      doctor and provides a modality to collect data from a larger number of patients
      than may be available at any single institution.

PMID- 17216577
TI  - Predictors of institutionalization in Latinos with dementia.
AB  - The present study identified predictors of time to institutionalization among
      elderly Latinos suffering from dementia, and determined how these predictors
      varied when compared to Caucasians and African-Americans. The sample included 324
      Latino, 701 African-American, and 7,100 Caucasian dementia patients and their
      caregivers recruited from eight catchment regions in the U.S. and were assessed
      over a 3-year period. Potential predictors considered in the event history
      analyses included context of care and indicators of care recipient cognitive and
      functional status, caregiver stress and depression, and caregiving resources. Cox
      proportional hazards models revealed that various indicators of sociodemographic
      context, caregiver well-being, and community-based service utilization influenced
      time to institutionalization among Latinos. Cross-ethnic/racial comparisons also
      identified statistical variations in site, living arrangement, intensity of
      informal care provision, caregiver depression, and adult day service use across
      the Latino, Caucasian, and African-American samples when predicting time to
      nursing home placement. The findings emphasize the need to explore time to
      institutionalization across racial and ethnic contexts, and suggest future
      variables to consider when analyzing nursing home placement in diverse
      situations.

PMID- 17216578
TI  - Bioactivity of CaSiO3/poly-lactic acid (PLA) composites prepared by various
      surface loading methods of CaSiO3 powder.
AB  - Mixing bioactive ceramic powders with polymers is an effective method for
      generating bioactivity to the polymer-matrix composites but it is necessary to
      incorporate up to 40 vol% of bioactive ceramic powder. However, such a high
      mixing ratio offsets the advantages of the flexibility and formability of polymer
      matrix and it would be highly advantageous to lower the mixing ratio. Since
      surface loading of ceramic powders in the polymer is thought to be an effective
      way of reducing the mixing ratio of the ceramic powder while maintaining
      bioactive activity, CaSiO(3)/poly-lactic acid (PLA) composites were prepared by
      three methods; (1) casting, (2) spin coating and (3) hot pressing. In methods (1)
      and (2), a suspension was prepared by dissolving PLA in chloroform and dispersing
      CaSiO(3) powder in it. The suspension was cast and dried to form a film in the
      case of method (1) while it was spin-coated on a PLA substrate in method (2). In
      method (3), CaSiO(3) powder was surface loaded on to a PLA substrate by hot
      pressing. The bioactivity of these samples was investigated in vitro using
      simulated body fluid (SBF). Apatite formation was not observed in the samples
      prepared by method (1) but some apatite formation was achieved by mixing
      polyethylene glycol (PEG) with the PLA, producing a porous polymer matrix. In
      method (2), apatite was clearly observed after soaking for 7 days. Enhanced
      apatite formation was observed in method (3), the thickness of the resulting
      apatite layers becoming about 20 microm after soaking for 14 days. Since the
      amount of CaSiO(3) powder used in these samples was only <or=0.4 vol%, it is
      concluded that this preparation method is very effective in generating
      bioactivity in polymer-matrix composites by loading with only very small amounts
      of ceramic powder.

PMID- 17216579
TI  - Development of a new calcium phosphate powder-binder system for the 3D printing
      of patient specific implants.
AB  - A key requirement for three-dimensional printing (3-DP) of medical implants is
      the availability of printable and biocompatible powder-binder systems. In this
      study we developed a powder mixture comprising tetracalcium phosphate (TTCP) as
      reactive component and beta-tricalcium phosphate (beta-TCP) or calcium sulfate as
      biodegradable fillers, which can be printed with an aqueous citric acid solution.
      The potential of this material combination was demonstrated printing various
      devices with intersecting channels and filigree structures. Two post-processing
      procedures, a sintering and a polymer infiltration process were established to
      substantially improve the mechanical properties of the printed devices.
      Preliminary examinations on relevant application properties including in vitro
      cytocompatibility testing indicate that the new powder-binder system represents
      an efficient approach to patient specific ceramic bone substitutes and scaffolds
      for bone tissue engineering.

PMID- 17216580
TI  - In vitro bioactivity of novel tricalcium silicate ceramics.
AB  - In this study, bone-like apatite-formation ability of tricalcium silicate
      (Ca(3)SiO(5)) ceramics in simulated body fluid (SBF) was evaluated and the in
      vitro degradability was investigated by soaking in Ringer's solution. The effect
      of ionic products from Ca(3)SiO(5) dissolution on osteobalsts proliferation was
      investigated. The result indicated that hydroxyapatite (HA) was formed on the
      surface of the Ca(3)SiO(5) ceramics after soaking in SBF for 1 day, and
      Ca(3)SiO(5) ceramics could degraded in Ringer's solution. The Si ions from
      Ca(3)SiO(5) dissolution at certain concentration range significantly stimulated
      osteoblasts proliferation. Our results show that Ca(3)SiO(5) ceramics possess
      bone-like apatite-formation ability and degradability, and can release soluble
      ionic products to stimulate cell proliferation.

PMID- 17216581
TI  - Biological response of new activated acrylic bone cements with antiseptic
      properties. Histomorphometric analysis.
AB  - The biological response to an acrylic bone cement cured with 4,4'-bis
      dimethylamino benzydrol (BZN) as activator of reduced cytotoxicity and antiseptic
      properties, has been carried out and compared with that obtained for CMW 3
      cement. Histomorphometrical data (undecalcified trichromic Goldner staining) were
      obtained by measuring the most significant variables at the bone-cement
      interface. Quantitative results of tissue response revealed that newly formed
      bone and connective tissue were maximum at 4 weeks whereas bone marrow increased
      with time of implantation for both cements. Statistical analysis (p < 0.05)
      showed no significant differences in newly formed bone and bone marrow with time
      and between both groups, however, connective tissue significantly decreased
      between 4 weeks and 12 weeks for BZN cement, and between 12 weeks and 24 weeks
      for CMW3. By comparing both cements at each time, lower significant percentage of
      connective tissue at the bone-cement interface of the BZN cement, was obtained at
      12 and 24 weeks, however, a very low amount of connective tissue was found for
      both cements. All the results indicate that the new activated system could be
      applied clinically in a relatively short time, after the corresponding
      preclinical study.

PMID- 17216582
TI  - Prevalence of adult problem and pathological gambling between 2000 and 2005: an
      update.
AB  - BACKGROUND: Excessive gambling is a prominent Public Health problem with high
      prevalence rates in many countries. Substance abuse and other co-morbidities
      often constitute a major health hazard for the person which gambles with a loss
      of material and social resources, as well as being a major concern for his or her
      significant others. The present study updates and extends prevalence data to
      include work published between 2000 and 2005 in English and other European
      languages. METHODS: In a three-step search and exclusion process, studies with
      current adult prevalence rates were gathered. RESULTS: Almost all studies fulfil
      basic research standards. The weighted mean prevalence rates for excessive
      gambling (problem and pathological) are 3.0% for the South Oaks Gambling Survey
      (problem 1.2%; pathological 1.8%), 3.3% for the Canadian Problem Gambling Index
      (problem 2.4%; pathological 0.8%) and 3.1% for the DSM-IV (problem 1.9%;
      pathological 1.2%). CONCLUSION: The prevalence rates are comparable and
      relatively stable between countries and across survey instruments, and do not
      differ from earlier reviews. The regular epidemiological monitoring of excessive
      gambling remains a major Public Health issue although the distinction between
      pathological and problem gambling is not appropriate for epidemiological
      research. Further studies are needed with respect to concomitant lifestyle
      characteristics.

PMID- 17216583
TI  - The functional haplotype of peptidylarginine deiminase IV (S55G, A82V and A112G)
      associated with susceptibility to rheumatoid arthritis dominates apoptosis of
      acute T leukemia Jurkat cells.
AB  - Peptidylarginine deiminase IV (PADI4) posttranslationally converts
      peptidylarginine to citrulline. It plays an essential role in immune cell
      differentiation and apoptosis. A haplotype of single-nucleotide polymorphisms
      (SNPs) in PADI4 is functionally relevant as a rheumatoid arthritis (RA) gene. It
      could increase enzyme activity leading to raised levels of citrullinated protein
      and stimulating autoantibody. Previously, our study showed that inducible PADI4
      causes haematopoietic cell death. Herein, we further investigate whether RA risk
      PADI4 haplotype (SNP PADI4; S55G, A82V and A112G) and the increase of its
      enzymatic activity induce apoptosis. In the tetracycline (Tet)-On Jurkat T cells,
      ionomycin (Ion) only treatment didn't induce apoptosis however it promoted
      inducible PADI4-decreased cell viability and -enhanced apoptosis. Through in
      vitro and in vivo PADI enzyme activity assay, we demonstrated that PADI4 enzyme
      activity of SNP PADI4 was higher than RA non-risk PADI4 haplotype (WT PADI4). The
      effect of SNP PADI4-induced apoptosis was superior to WT PADI4. In addition, both
      Ion and SNP PADI4 synergistically provoked apoptosis were compared with both Ion
      and WT PADI4. Concurrently, in the conditionally inducible SNP PADI4 cells of Ion
      treatment-induced apoptosis, not only the expression of Bcl-xL was down-regulated
      and Bax up-regulated, but also cytochrome c was released from mitochondria to
      cytoplasm in significant amounts. Western blotting data showed the increase in
      apoptosomal caspase activation during programmed cell death in the inducible SNP
      PADI4 cells subsequent to Ion treatment. These data demonstrated that both SNP
      PADI4 increasing their enzyme activity could enhance apoptosis through the
      mitochondrial pathway and further provide a conceivable explanation in the
      pathogenesis of RA following the upregulation of PADI4 activity in its SNPs.

PMID- 17216584
TI  - Role of Noxa in p53-independent fenretinide-induced apoptosis of neuroectodermal
      tumours.
AB  - Fenretinide-induced apoptosis of neuroectodermal tumour cells is mediated through
      generation of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress,
      mitochondrial cytochrome c release and caspase activation. The present study
      describes the requirement of the BH3-domain only protein Noxa for this process
      and its regulation by p53. Noxa expression was induced by fenretinide in
      neuroblastoma and melanoma cells, including those with mutated p53, and this
      induction was abolished by antioxidants. Knockdown of p53 by RNA interference
      (RNAi) demonstrated upregulation of Noxa protein levels in response to
      fenretinide was p53-independent, although evidence suggested that Noxa may be
      transcriptionally regulated by p53. The ER stress-inducing agent thapsigargin
      also induced p53-independent Noxa expression. Conversely, Noxa transcription in
      response to the chemotherapeutic agents cisplatin or temozolomide was inhibited
      by p53 knockdown. Apoptosis in response to cisplatin or temozolomide was also
      inhibited by abrogation of p53 expression yet apoptosis in response to
      fenretinide or thapsigargin was unaffected. RNAi-mediated down-regulation of Noxa
      inhibited apoptosis in response to fenretinide or thapsigargin, whereas apoptosis
      induced by cisplatin or temozolomide was unaffected. These data demonstrate the
      importance of Noxa induction in determining the apoptotic response to fenretinide
      and emphasise the role of Noxa in p53-independent apoptosis.

PMID- 17216585
TI  - Implications of deep electrode insertion on cochlear implant fitting.
AB  - Using long Med-El Combi40+ electrode arrays, it is now possible to cover the
      whole range of the cochlea, up to about two turns. Such insertion depths have
      received little attention. To evaluate the contribution of deeply inserted
      electrodes, five Med-El cochlear implant users were tested on vowel and consonant
      identification tests with fittings with first one, two, and up to five apical
      electrodes being deactivated. In addition, subjects performed pitch-ranking
      experiments, using loudness-balanced stimuli, to identify electrodes creating
      pitch confusions. Radiographs were taken to measure each electrode insertion
      depth. All subjects used each modified fitting for two periods of about 3 weeks.
      During the experiment, the same stimulation rate and frequency range were
      maintained across all the fittings used for each individual subject. After each
      trial period the subject had to perform three consonant and three vowel
      identification tests. All subjects showed deep electrode insertions ranging from
      605 degrees to 720 degrees. The two subjects with the deepest electrode
      insertions showed significantly increased vowel- and consonant-identification
      performances with fittings with the two or three most apical electrodes
      deactivated compared to their standard fitting with all available electrodes
      activated. The other three subjects did not show significant improvements in
      performance when one or two of their most apical electrodes were deactivated.
      Four out of five subjects preferred to continue use of a fitting with one or more
      apical electrodes deactivated. The two subjects with the deepest insertions also
      showed pitch confusions between their most apical electrodes. Two possible
      reasons for these results are discussed. One is to reduce neural interactions
      related to electrodes producing pitch confusions. Another is to improve the
      alignment of the frequency components of sounds coded by the electrical signals
      delivered to each electrode to the overall pitch of the auditory perception
      produced by the electrical stimulation of auditory nerve fibers.

PMID- 17216586
TI  - Part 2. Automated change detection and characterization applied to serial MR of
      brain tumors may detect progression earlier than human experts.
AB  - An algorithm was developed which compares serial MRI brain examinations of brain
      tumor patients and judges them as either "stable" or "progressing". A set of 88
      serial MR cases were obtained, consisting of cases which were stable and remained
      stable for at least 8 months, cases which were stable but progressed in less than
      8 months, and cases which were progressing. The algorithm was run and its output
      was compared to the original clinical interpretation. Of the exam pairs which
      were judged stable and which remained stable at least 8 months after the later
      examination, the algorithm diagnosed 45/46 as stable. For exam pairs judged to be
      progressing, the algorithm judged 15/17 to be progressing. Of the exam pairs
      which were judged stable, but which went on to progress less than 8 months after
      the later of the pair, 16/25 were judged by the algorithm to be progressing.

PMID- 17216587
TI  - [Compulsory treatment in anorexia nervosa].
AB  - Anorexia nervosa is a psychiatric disorder with a very high mortality rate. If
      the eating disorder reaches life-threatening severity, for example through a body
      mass index lower than 13 kg/m (2), the possibility of compulsory treatment has to
      be considered. However, civil commitment of patients and forced feeding against
      their will may reduce self confidence and self esteem. This impedes the important
      goal of motivating patients to undergo psychotherapy. Furthermore, compulsory
      treatment is regarded as a contravention of the patient's physical inviolability
      as enshrined in the German Constitution. Up to now only a few studies about the
      use of guardianship legislation for anorexia nervosa have been published. The
      present paper reviews psychiatric literature and significant judgements of German
      courts on this topic. It finishes by examining clinical issues on forced feeding
      and possible consequences for psychotherapy.

PMID- 17216588
TI  - [How are dysfunctional relationship patterns re-enacted in the therapist-patient
      interaction?].
AB  - Using Structural Analysis of Social Behaviour (SASB), the communicative means by
      which a patient succeeds in re-enacting his or her own maladaptive relationship
      patterns in the interaction with the therapist is examined. This line of
      investigation stems from the work of Henry and co-workers, who have shown that
      therapists often unknowingly allow themselves to be drawn into subtly hostile
      interactions with patients, and that such interactions are associated with a
      negative outcome. In a mixed quantitative-qualitative single case study, the
      relationship narratives of a female patient from two therapy sessions are
      analysed using a cluster-analytic procedure in order to identify her repetitive
      relationship patterns. Then, using a short sequence of interaction, it is
      demonstrated how a central maladaptive pattern is re-enacted in the therapeutic
      interaction and gradually takes hold. These results are interpreted as evidence
      that patient communication contains paradoxical demands which can lead therapists
      to become part of the maladaptive pattern of interaction.

PMID- 17216590
TI  - Comparison of the efficacy of enrofloxacin, imidocarb, and oxytetracycline for
      clearance of persistent Anaplasma marginale infections in cattle.
AB  - This study compared enrofloxacin and imidocarb dipropionate treatments with an
      oxytetracycline regimen proposed by the World Organization for Animal Health for
      elimination of persistent Anaplasma marginale infections in cattle. The effect of
      therapy on competitive ELISA and polymerase chain reaction (PCR) reactivity was
      also assessed. Twelve A. marginale-infected carrier calves were randomly assigned
      to groups receiving either enrofloxacin (5 mg/kg IV q24h for 5 days), imidocarb
      (5 mg/kg IM twice, 7 days apart), or oxytetracycline (22 mg/kg IV q24h for 5
      days). One calf infected with an Oklahoma isolate in the imidocarb group and one
      infected with a Virginia isolate in the oxytetracycline group failed to infect a
      splenectomized calf following blood subinoculation. Both became competitive ELISA
      negative by 44 days after treatment, but the imidocarb-treated calf remained PCR
      positive. None of the tested treatments reliably eliminated persistent A.
      marginale infections in all cattle. Furthermore, PCR was not a reliable means of
      determining the success of chemosterilization in calves.

PMID- 17216589
TI  - Effects of sodium chloride on selected parameters in cats.
AB  - This study used 36 cats with varying renal insufficiency and physiologic status
      to evaluate the effect of a food high in sodium chloride (HSC) compared with a
      low sodium chloride (LSC) food on selected blood parameters and blood pressure.
      Cats eating the HSC food had an increase in serum creatinine, urea nitrogen, and
      phosphorus compared with cats eating the LSC food. Also, cats eating the HSC food
      had increased fractional excretion of calcium and increased fractional shortening
      during cardiac contraction. There was no effect of food on systolic, diastolic,
      or mean arterial pressure.

PMID- 17216591
TI  - Effect of hyperimmune plasma on the severity of pneumonia caused by Rhodococcus
      equi in experimentally infected foals.
AB  - This study evaluated the prophylactic effectiveness of hyperimmune plasma (HIP)
      as an aid in the prevention of pneumonia caused by experimental infection with
      Rhodococcus equi. Thirty neonatal foals were administered R. equi HIP or saline
      at 2 days of age and were infected with virulent R. equi at 7 days. All foals
      developed signs or symptoms of respiratory disease. Radiographic scores on day 28
      and neutrophil concentrations on day 49 were significantly greater in control
      foals, and time to respiratory effort score of 2 or higher was significantly
      shorter for control foals. Three foals, all in the principal group, died or were
      euthanized before the end of the study, but there was no significant difference
      in mortality between groups. VapA titers were significantly greater in principal
      foals. Administration of R. equi HIP decreased the severity of radiographic
      lesions and prolonged time to increased respiratory effort due to R. equi-induced
      pneumonia.

PMID- 17216592
TI  - Multivariate scan statistics for disease surveillance.
AB  - In disease surveillance, there are often many different data sets or data
      groupings for which we wish to do surveillance. If each data set is analysed
      separately rather than combined, the statistical power to detect an outbreak that
      is present in all data sets may suffer due to low numbers in each. On the other
      hand, if the data sets are added by taking the sum of the counts, then a signal
      that is primarily present in one data set may be hidden due to random noise in
      the other data sets. In this paper, we present an extension of the spatial and
      space-time scan statistic that simultaneously incorporates multiple data sets
      into a single likelihood function, so that a signal is generated whether it
      occurs in only one or in multiple data sets. This is done by defining the
      combined log likelihood as the sum of the individual log likelihoods for those
      data sets for which the observed case count is more than the expected. We also
      present another extension, where the concept of combining likelihoods from
      different data sets is used to adjust for covariates. Using data from the
      National Bioterrorism Syndromic Surveillance Demonstration Project, we illustrate
      the new method using physician telephone calls, regular physician visits and
      urgent care visits by Harvard Pilgrim Health Care members cared for by Harvard
      Vanguard Medical Associates, a large multi-specialty group practice in
      Massachusetts. For upper and lower gastrointestinal (GI) illness, there were on
      average 20 telephone calls, nine urgent care visits and 22 regular physician
      visits per day. The strongest signal was generated by a single data set and due
      to a familial outbreak of pinworm disease. The second and third strongest signals
      were generated by the combined strength of two of the three data sets.

PMID- 17216593
TI  - Allergy reactions to insulin: effects of continuous subcutaneous insulin infusion
      and insulin analogues.
AB  - The purification of animal insulin preparations and the use of human recombinant
      insulin have markedly reduced the incidence but not completely suppressed the
      occurrence of insulin allergy manifestations. Advances in technologies concerning
      the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion
      (CSII), and the use of insulin analogues, resulting from the alteration in the
      amino acid sequence of the native insulin molecule, may influence the
      immunogenicity and antigenicity of native insulin. Instead of increasing allergy
      reactions, CSII has been reported to represent a successful alternative treatment
      in diabetic patients presenting local or generalized allergy to insulin or other
      components (zinc, protamine) of conventional treatment. Most recent reports
      concern CSII-treated patients using short-acting insulin analogues (essentially
      insulin lispro), although the precise role of these insulin analogues remains
      unclear as allergy to them has also been described. Finally, data on antigenicity
      and immunogenicity of long-acting insulin analogues (glargine, detemir), which
      may mimic the basal insulin delivery with CSII, remain scarce at present.

PMID- 17216594
TI  - A repeated measures concordance correlation coefficient.
AB  - The concordance correlation coefficient is commonly used to assess agreement
      between two raters or two methods of measuring a response when the data are
      measured on a continuous scale. However, the situation may arise in which
      repeated measurements are taken for each rater or method, e.g. longitudinal
      studies in clinical trials or bioassay data with subsamples. This paper proposes
      a coefficient for measuring agreement between two raters or two methods of
      measuring a response in the presence of repeated measurements. We illustrate the
      methodology with examples comparing (1) 1-hr versus 2-hr blood draws for
      measuring cortisol in an asthma clinical trial and (2) two measurements of
      percentage body fat, from skinfold calipers and dual energy X-ray absorptiometry.

PMID- 17216595
TI  - Metalloproteinases are enriched in microglia compared with leukocytes and they
      regulate cytokine levels in activated microglia.
AB  - Microglia are resident immune cells within the central nervous system (CNS). They
      become activated following neurological insults and increase their expression of
      cytokines. Also elevated in CNS injuries are proteases, including matrix
      metalloproteinases (MMPs) and A disintegrin and metalloproteinases (ADAMs). The
      spectrum of metalloproteinase members expressed by microglia and by the systemic
      leukocytes that infiltrate the injured CNS is unknown, as are their functions. We
      determined the levels of transcripts encoding all 24 MMPs, nine ADAMs, and their
      four physiological antagonists, tissue inhibitor of metalloproteinases (TIMPs),
      in human microglia, B and T cells, monocytes, and neutrophils. We found a
      distinct pattern for each immune subset and an enrichment of metalloproteinases
      in microglia compared with leukocytes. When microglia were activated, there was
      an upregulation of transcripts for nine metalloproteinases, and reduction of
      TIMP3. Activation of microglia also resulted in increased levels of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-10 protein in the
      conditioned media of cells. The amount of secreted TNF-alpha, but not IL-1beta or
      IL-10, was suppressed by BB94, a broad spectrum metalloproteinase inhibitor, and
      by TIMP3 but not TIMP1 or TIMP2. This inhibitory profile suggests the involvement
      of an ADAM member in TNF-alpha secretion. We conclude that microglia bear a
      metalloproteinase signature distinct from systemic cells, and that following
      activation, microglia upregulate TNF-alpha protein levels through a combination
      of elevated cytokine transcripts, increased metalloproteinase level and activity,
      and through the decrease of TIMP3. The results have implications for the
      regulation of neuroinflammation and its outcomes following CNS injuries.

PMID- 17216596
TI  - The calibration of the intramolecular nitrogen isotope distribution in nitrous
      oxide measured by isotope ratio mass spectrometry.
AB  - Two alternative approaches for the calibration of the intramolecular nitrogen
      isotope distribution in nitrous oxide using isotope ratio mass spectrometry have
      yielded a difference in the 15N site preference (defined as the difference
      between the delta15N of the central and end position nitrogen in NNO) of
      tropospheric N2O of almost 30 per thousand. One approach is based on adding small
      amounts of labeled 15N2O to the N2O reference gas and tracking the subsequent
      changes in m/z 30, 31, 44, 45 and 46, and this yields a 15N site preference of
      46.3 +/- 1.4 per thousand for tropospheric N2O. The other involves the synthesis
      of N2O by thermal decomposition of isotopically characterized ammonium nitrate
      and yields a 15N site preference of 18.7 +/- 2.2 per thousand for tropospheric
      N2O. Both approaches neglect to fully account for isotope effects associated with
      the formation of NO+ fragment ions from the different isotopic species of N2O in
      the ion source of a mass spectrometer. These effects vary with conditions in the
      ion source and make it impossible to reproduce a calibration based on the
      addition of isotopically enriched N2O on mass spectrometers with different ion
      source configurations. These effects have a much smaller impact on the comparison
      of a laboratory reference gas with N2O synthesized from isotopically
      characterized ammonium nitrate. This second approach was successfully replicated
      and leads us to advocate the acceptance of the site preference value 18.7 +/- 2.2
      per thousand for tropospheric N2O as the provisional community standard until
      further independent calibrations are developed and validated. We present a
      technique for evaluating the isotope effects associated with fragment ion
      formation and revised equations for converting ion signal ratios into isotopomer
      ratios.

PMID- 17216597
TI  - A combined nuclear magnetic resonance and computational study of
      monohydroxyflavones applied to product ion mass spectra.
AB  - A method is presented for the estimation of 13C-chemical shifts for carbon atoms
      in protonated and deprotonated molecules; in principle, this method can be
      applied to ions in general. Experimental 13C-chemical shifts were found to vary
      linearly with computed atomic charges using the PM3 method. Pseudo-13C-chemical
      shifts for atoms in protonated and deprotonated molecules can be estimated from
      computed atomic charges for such atoms using the above linear relationship. The
      pseudo-13C-chemical shifts obtained were applied to the rationalization of
      product ion mass spectra of protonated and deprotonated molecules of flavone and
      3-, 5-, 6-, 7-, 2'-, 3'-, and 4'-hydroxyflavones, where product ion formation is
      due to either cross-ring cleavage of the C-ring (retro-Diels-Alder reaction) or
      to cleavage of a C-ring bond followed by loss of either a small neutral molecule
      or a radical. The total product ion abundance ratio of C-ring cross cleavage to C
      ring bond cleavage, gamma, varied by a factor of 660 for deprotonated
      monohydroxyflavones, i.e., from 0.014:1 to 9.27:1. The magnitude of gamma, which
      is dependent on the relative bond orders within the C-ring of the protonated and
      deprotonated molecules of monohydroxyflavones, can be rationalized on the basis
      of the magnitudes of the 13C- and 1H-chemical shifts as determined by nuclear
      magnetic resonance spectroscopy.

PMID- 17216599
TI  - Osteonecrosis in children with acute lymphoblastic leukemia: a 10-year study from
      northern Greece.

PMID- 17216598
TI  - CCR2 expression correlates with prostate cancer progression.
AB  - Although the primary role of chemokines and their receptors is controlling the
      trafficking of leukocytes during inflammatory responses, they also play
      pleoitropic roles in cancer development. There is emerging evidence that cancer
      cells produce chemokines that induce tumor cell proliferation or chemotaxis in
      various cancer types. We have previously reported that MCP-1 acts as a paracrine
      and autocrine factor for prostate cancer (PCa) growth and invasion. As the
      cellular effects of MCP-1 are mediated by CC chemokine receptor 2 (CCR2), we
      hypothesized that CCR2 may contribute PCa progression. Accordingly, we first
      determined CCR2 mRNA and protein expression in various cancer cell lines,
      including PCa and other cancer types. All cells expressed CCR2 mRNA and protein,
      but in PCa, more aggressive cancer cells such as C4-2B, DU145, and PC3 expressed
      a higher amount of CCR2 compared with the less aggressive cancer cells such as
      LNCaP or non-neoplastic PrEC and RWPE-1 cells. Further, we found a positive
      correlation between CCR2 expression and PCa progression by analyzing an ONCOMINE
      gene array database. We confirmed that CCR2 mRNA was highly expressed in PCa
      metastatic tissues compared with the localized PCa or benign prostate tissues by
      real-time RT-PCR. Finally, CCR2 protein expression was examined by
      immunohistochemical staining on tissue microarray specimens from 96 PCa patients
      and 31 benign tissue controls. We found that CCR2 expression correlated with
      Gleason score and clinical pathologic stages, whereas lower levels of CCR2 were
      expressed in normal prostate tissues. These results suggest that CCR2 may
      contribute to PCa development.

PMID- 17216600
TI  - Increased expression of activating factors in large osteoclasts could explain
      their excessive activity in osteolytic diseases.
AB  - Large osteoclasts (>or=10 nuclei) predominate at sites of pathological bone
      resorption. We hypothesized this was related to increased resorptive activity of
      large osteoclasts and have demonstrated previously that larger osteoclasts are 8
      fold more likely to be resorbing than small osteoclasts (2-5 nuclei). Here we ask
      whether these differences in resorptive activity can be explained by differences
      in expression of factors involved in osteoclast signaling, fusion, attachment,
      and matrix degradation. Authentic rabbit osteoclasts and osteoclasts derived from
      RAW264.7 cells showed similar increases in c-fms expression (1.7- to 1.8-fold) in
      large osteoclasts suggesting that RAW cells are a viable system for further
      analysis. We found 2- to 4.5-fold increases in the expression of the integrins
      alpha(v) and beta(3), the proteases proMMP9, matMMP9 and pro-cathepsinK, and in
      activating receptors RANK, IL-1R1, and TNFR1 in large osteoclasts. In contrast,
      small osteoclasts had higher expression of the fusion protein SIRPalpha1 and the
      decoy receptor IL-1R2. The higher expression of activation receptors and lower
      expression of IL-1R2 in large osteoclasts suggest they are hyperresponsive to
      extracellular factors. This is supported by the observation that the resorptive
      activity in large osteoclasts was more responsive to IL-1beta, and that this
      increased activity was inhibited by the IL-1 receptor antagonist, IL-1ra. This
      increased responsiveness of large osteoclasts to IL-1 may, in part, explain the
      pathological bone loss noted in inflammatory diseases. The heterogeneity in
      receptor expression and the differential response to cytokines and their
      antagonists could prove useful for selective inhibition of large osteoclasts
      actively engaged in pathological bone loss.

PMID- 17216601
TI  - Characterization of liver disease and lipid metabolism in the Niemann-Pick C1
      mouse.
AB  - Niemann-Pick type C1 (NPC1) disease is an autosomal-recessive cholesterol-storage
      disorder characterized by liver dysfunction, hepatosplenomegaly, and progressive
      neurodegeneration. The NPC1 gene is expressed in every tissue of the body, with
      liver expressing the highest amounts of NPC1 mRNA and protein. A number of
      studies have now indicated that the NPC1 protein regulates the transport of
      cholesterol from late endosomes/lysosomes to other cellular compartments involved
      in maintaining intracellular cholesterol homeostasis. The present study
      characterizes liver disease and lipid metabolism in NPC1 mice at 35 days of age
      before the development of weight loss and neurological symptoms. At this age,
      homozygous affected (NPC1(-/-)) mice were characterized with mild hepatomegaly,
      an elevation of liver enzymes, and an accumulation of liver cholesterol
      approximately four times that measured in normal (NPC1(+/+)) mice. In contrast,
      heterozygous (NPC1(+/-)) mice were without hepatomegaly and an elevation of liver
      enzymes, but the livers had a significant accumulation of triacylglycerol. With
      respect to apolipoprotein and lipoprotein metabolism, the results indicated only
      minor alterations in NPC1(-/-) mouse serum. Finally, compared to NPC1(+/+) mouse
      livers, the amount and processing of SREBP-1 and -2 proteins were significantly
      increased in NPC1(-/-) mouse livers, suggesting a relative deficiency of
      cholesterol at the metabolically active pool of cholesterol located at the
      endoplasmic reticulum. The results from this study further support the hypothesis
      that an accumulation of lipoprotein-derived cholesterol within late
      endosomes/lysosomes, in addition to altered intracellular cholesterol
      homeostasis, has a key role in the biochemical and cellular pathophysiology
      associated with NPC1 liver disease.

PMID- 17216602
TI  - Ligularia fischeri leaf extract prevents the oxidative stress in DBA/1J mice with
      type II collagen-induced arthritis.
AB  - The generation of free radicals has been implicated in the causation of several
      diseases and compounds that can scavenge free radicals have great potential in
      ameliorating these disease processes. The present study was aimed to investigate
      the possible antioxidant potential of Ligularia fischeri leaves on collagen type
      II induced arthritis (CIA) in DBA/1J mice. Ligularia fischeri extracts (100 and
      200 mg kg(-1)) were orally administered to DBA/1J mice once daily for 49 days
      after initial immunization with type II collagen. The levels of oxidant products
      and the activities of antioxidant enzymes were determined in the serum and organs
      obtained at day 50. The induction of arthritis significantly increased
      malondialdehyde (MDA) in the serum and kidney, and oxidized proteins such as
      protein carbonyl (PCO) and advanced glycation end-products (AGE) in the serum,
      liver, spleen and kidney. Oral administration of Ligularia fischeri extract at
      doses of 100 and 200 mg kg(-1) reduced the levels of MDA in the serum and kidney,
      and PCO and AGE in the serum, liver, and kidney compared with CIA mice. Moreover,
      treatment with Ligularia fischeri extract dose-dependently increased the
      activities of superoxide dismutase, glutathione peroxidase and glutathione
      reductase in the spleen compared with CIA mice. These results suggest that
      Ligularia fischeri exerts antioxidant actions in the CIA mouse model.

PMID- 17216603
TI  - Optimization of spatiotemporal gene inactivation in mouse heart by oral
      application of tamoxifen citrate.
AB  - Inducible and tissue-specific gene inactivation in mice has become a powerful
      tool to bypass embryonic and postnatal lethality of knockout mice. The most
      frequently used inducible system is based on Cre recombinase fused to either one
      or two mutated estrogen receptor ligand binding domains, thus rendering Cre
      function tamoxifen-dependent. To achieve Cre-mediated inactivation of a given
      gene, 4-OH tamoxifen (4-OHT) dissolved either in alcohol and/or oil is usually
      administered by repeated intraperitoneal (i.p.) injections. Since this procedure
      imposes considerable stress on mice, we compared the effect of tamoxifen citrate,
      mixed into a standard mouse diet at different concentrations, with that of i.p.
      administration of 4-OHT on Cre-mediated, heart-specific inactivation of
      thioredoxin reductase 2. Here we show that tamoxifen citrate in the chow was
      equally effective as 4-OHT given i.p. Oral tamoxifen administration is thus a
      convenient and cost-saving way for gene induction, and, most importantly, it
      reduces stress and avoids adverse effects in mice.

PMID- 17216604
TI  - The effect of alpha-melanocyte stimulating hormone on gentamicin-induced acute
      nephrotoxicity in rats.
AB  - The effect of alpha-melanocyte stimulating hormone (alpha-MSH) was investigated
      on gentamicin-induced acute renal injury in rats. Sprague-Dawley rats (200-250 g;
      n = 8-10) were treated with gentamicin sulphate (GEN; 80 mg kg(-1)) or saline
      intraperitoneally for 7 consecutive days. alpha-MSH was administered at a dose of
      25 microg rat(-1) day(-1) following GEN or saline injections. On day 8, all
      animals were decapitated. Trunk blood and 24 h urine were collected to measure
      the serum creatinine levels, blood urea nitrogen (BUN) levels and to calculate
      the creatinine clearance values. The kidneys were excised for histological
      evaluation and for the measurement of malondialdehyde (MDA) levels, glutathione
      (GSH) contents and myeloperoxidase (MPO) activity. Treatment with alpha-MSH
      reduced the severity of the renal lesions microscopically, decreased MDA content
      and MPO activity and restored GSH in kidney samples. However, it did not restore
      the impaired renal function tests due to GEN challenge. In conclusion, alpha-MSH
      treatment has a beneficial effect on GEN-induced acute nephrotoxicity, as
      confirmed by histological evaluation and biochemical assays; but it does not
      improve GEN-induced renal dysfunction. The mechanism of the protective effect
      could be attributed, at least in part, to decreased tissue leukocyte infiltration
      and thus, to decreased oxygen-derived reactive metabolite production.

PMID- 17216605
TI  - Knock-in mice reveal nonsense-mediated mRNA decay in the brain.
AB  - Nonsense-mediated mRNA decay (NMD) is a process of mRNA surveillance that
      degrades transcripts harboring a premature termination codon (PTC). Mammalian NMD
      was mostly studied in cultured cells so far and there was no direct evidence yet
      that NMD could operate in the brain. We introduced, by homologous recombination
      in mouse, a PTC in the mu opioid receptor gene (mor). mor transcript was severely
      downregulated in the brain of these knock-in mice. A systemic cycloheximide
      treatment significantly increased the level of the mutant mRNA, suggesting NMD
      involvement. To further corroborate this hypothesis, we generated a second knock
      in mouse line where the PTC was placed at 10 instead of 96 nucleotides from the
      downstream splice junction. As predicted by the "termination codon position rule"
      established in vitro, mor transcript brain expression was rescued to wild-type
      level. These knock-in mouse lines will be valuable models to better understand
      and manipulate NMD in vivo.

PMID- 17216606
TI  - Investigation of acute toxicity of fenitrothion on guppies Poecilia reticulata.
AB  - Fenitrothion, an organophosphothionate insecticide (CAS number: 122-14-5) and
      potential toxic pollutant contaminating aquatic ecosystems, was investigated in
      the present study for acute toxicity. Guppy fish (Poecilia reticulata) were
      selected for the bioassay experiments. The experiments were repeated three times
      and the 96 h LC(50) was determined for the guppies. The static test method of
      acute toxicity test was used. The water temperature was regulated at 23 +/- 1
      degrees C. In addition, behavioral changes at each fenitrothion concentration
      were observed for the individual fish. Data obtained from the fenitrothion acute
      toxicity tests were evaluated using the probit analysis statistical method. The
      96 h LC(50) value for guppy was estimated as 3.28 mg l(-1). Values in the range
      of microg l(-1) and mg l(-1) have been reported for various other fish species.

PMID- 17216607
TI  - A Sall4 mutant mouse model useful for studying the role of Sall4 in early
      embryonic development and organogenesis.
AB  - SALL4 is a homologue of the Drosophila homeotic gene spalt, a zinc finger
      transcription factor, required for inner cell mass proliferation in early
      embryonic development. It also interacts with other transcription factors to
      control the development of the anorectal region, kidney, heart, limbs, and brain.
      Truncating mutations in SALL4 cause Okihiro syndrome, manifest as Duane anomaly,
      radial ray defects and sensorineural and conductive deafness. We report the
      characterization of a novel murine Sall4 null allele created by bacterial
      recombineering in ES cells. Homozygous mutant mice exhibit early embryonic
      lethality. Heterozygous mutant mice recapitulate phenotypic features of Okihiro
      syndrome including deafness, lower anogenital tract abnormalities, renal
      hypoplasia, anencephaly, Hirschprung's disease, and skeletal defects. This
      phenotype shows important differences in cardiac and ear manifestations to
      previously characterized Sall4 mutant alleles and should prove useful for the
      investigation of the influence of modifier alleles and protein interactions on
      the transcriptional regulatory function of Sall4.

PMID- 17216608
TI  - The effects of erdosteine, N-acetylcysteine and vitamin E on nicotine-induced
      apoptosis of cardiac cells.
AB  - This study was conducted to investigate the frequency of apoptosis in rat
      cardiomyocytes after intratraperitoneal nicotine injection, in order to examine
      the roles of inflammatory markers [myeloperoxidase (MPO) and tumor necrosis
      factor alpha (TNF-alpha)] in nicotine-induced cardiac damage and to determine the
      protective effects of three known antioxidant agents (N-acetylcysteine (NAC),
      erdosteine and vitamin E) on nicotine toxicity in the heart. Female Wistar rats
      were divided into seven groups, each composed of nine rats: two negative control
      groups, two positive control groups, one erdosteine-treated group (500 mg kg(
      1)), one NAC-treated group (500 mg kg(-1)) and one vitamin E-treated group (500
      mg kg(-1)). Nicotine was intraperitoneally injected at a dosage of 0.6 mg kg(-1)
      for 21 days. Following nicotine injection, the antioxidants were administered
      orally; treatment was continued until the rats were killed. Heart tissue samples
      were stained with hematoxylin-eosin for histopathological assessments. Apoptosis
      level in cardiomyocytes was determined by using TUNEL (terminal deoxynucleotidyl
      transferase-mediated dUTP nick endlabelling) method. Staining of cytoplasmic TNF
      alpha in cardiomyocytes and heart MPO activity were evaluated by
      immunohistochemistry. The treatments with erdosteine, NAC and vitamin E
      significantly reduced the rate of nicotine-induced cardiomyocyte apoptosis. The
      effect of vitamin E on apoptosis regulation was weaker than the effects of
      erdosteine and NAC. Erdosteine, NAC and vitamin E significantly reduced the
      increases in the local production of TNF-alpha and heart MPO activity. This
      findings suggest that the effects of erdosteine and NAC on apoptosis regulation
      are stronger than that of vitamin E.

PMID- 17216610
TI  - Mobile phone ownership and use among school children in three Hungarian cities.
AB  - In spite of rapid worldwide increase in mobile phone use and public concerns
      about associated potential health effects, little is known about patterns of
      mobile phone ownership and use in the general population and among children. In
      April 2005, we conducted a survey of mobile phone ownership and use among fourth
      grade school children in three Hungarian cities. From 24 schools, 1301 student
      filled out a short, self-administered questionnaire on basic demographics, mobile
      phone ownership, pattern of mobile phone use, and after-school activities.
      Overall, 989 students (76%) owned a mobile phone. Three hundred thirteen students
      (24%) used a mobile phone daily to make phone calls, and an additional 427
      students (33%) used mobile phones for phone calls at least several times per
      week. Sixty-six students (5%) sent text messages daily and an additional 308
      students (24%) sent text messages at least several times per week. Girls,
      children with no siblings, children who were members of a sport club, and
      children who played computer games daily were more likely to own and use mobile
      phones regularly. A higher number of socially disadvantaged children in a class
      predicted lower likelihood of regular mobile phone use among children. Our
      results suggest that mobile phone ownership and regular use is highly prevalent
      among school children in Hungary. Due to rapid changes in ownership patterns
      follow up surveys will be required to obtain information on temporal trends and
      changes in mobile phone ownership and pattern of use among school children.

PMID- 17216609
TI  - Effects of short- and long-term pulsed radiofrequency electromagnetic fields on
      night sleep and cognitive functions in healthy subjects.
AB  - There has been wide public discussion on whether the electromagnetic fields of
      mobile telephones and their base stations affect human sleep or cognitive
      functioning. As there is evidence for learning and memory-consolidating effects
      of sleep and particularly of REM sleep, disturbance of sleep by radiofrequency
      electromagnetic fields might also impair cognitive functions. Previously realized
      sleep studies yielded inconsistent results regarding short-term exposure.
      Moreover, data are lacking on the effect that short- and long-term exposure might
      have on sleep as well as on cognitive functions. Therefore, 10 healthy young male
      subjects were included and nocturnal sleep was recorded during eight consecutive
      nights. In the second, third, and last night, we investigated polysomnographic
      night sleep and cognitive functions. After the adaptation and baseline nights,
      the participants were exposed to a defined radiofrequency electromagnetic field
      during the following six nights. We analyzed polysomnographic night sleep
      according to Rechtschaffen and Kales [1968, Manual of Standardized Terminology,
      Techniques and Scoring System for Sleep of Human Subjects] as well as by power
      spectra and correlation dimension. Cognitive functions were investigated by an
      array of neuropsychological tests. Data analysis was done by comparing the
      baseline night with the first and last exposure night and the first two sleep
      cycles of the respective nights. We did not find significant effects, either on
      conventional sleep parameters or on power spectra and correlation dimension, nor
      were there any significant effects on cognitive functions. With our results, we
      are unable to reveal either short-term or cumulative long-term effects of
      radiofrequency electromagnetic fields on night sleep and cognitive functions in
      healthy young male subjects.

PMID- 17216611
TI  - Complex interference in the eye developmental pathway by Drosophila NF-YA.
AB  - The CCAAT motif-binding factor NF-Y consists of three different subunits, NF-YA,
      NF-YB, and NF-YC, all of which are required for formation of the NF-Y complex and
      DNA-binding. NF-YA contains a DNA binding domain in its C-terminal region. We
      established transgenic fly lines carrying the UAS-HA-dNF-YA or UAS-dNF-YAIR and
      showed over-expression or knockdown with various GAL4 drivers to be lethal at
      various developmental stages, suggesting that dNF-YA participate in various gene
      regulatory pathways during Drosophila development. Expression of dNF-YA with
      eyeless-GAL4 mainly resulted in lethality with a headless phenotype in pharate
      adults. Reduction of the eyeless gene dose enhanced the dNF-YA-induced phenotype,
      while reduction of the Distal-less gene dose suppressed the phenotype. On the
      other hand, crossing the dNF-YA over-expressing flies with Notch mutant resulted
      in no apparent effect on the phenotype. These results suggest that dNF-YA can
      disturb eye disc specification, but not eye disc growth.

PMID- 17216615
TI  - Human CYP11A1 promoter drives Cre recombinase expression in the brain in addition
      to adrenals and gonads.
AB  - The first step of steroid biosynthesis is catalyzed by cytochrome P450scc,
      encoded by CYP11A1. To achieve steroidogenic tissue-specific inactivation of
      genes in vivo by the Cre-loxP approach, we used the 4.4-kb regulatory region of
      the human CYP11A1 gene to drive Cre recombinase expression in the tissues that
      produce steroids. The resulting SCC-Cre mice express high levels of Cre in the
      adrenal cortex and gonads at the same sites as that for the endogenous CYP11A1
      expression. In addition, Cre activity was found in the diencephalon and midbrain.
      In the developing brain, the Cre activity was first detected in the embryonic day
      10.5. Our study is the first to show that the 4.4-kb CYP11A1 promoter is
      transcriptionally active in the brain in vivo.

PMID- 17216616
TI  - Case-control genetic association study of fibulin-6 (FBLN6 or HMCN1) variants in
      age-related macular degeneration (AMD).
AB  - This article reports a well-powered age-related macular degeneration (AMD) case
      control association study in the HMCN1 gene, showing that common variants do not
      account for a substantial proportion of AMD cases. Thus, the consistent linkage
      peak observed by several genome-wide linkage scans within the 1q32 region is
      unlikely to be attributed to polymorphisms at the HMCN1 locus. In addition, the
      analysis provides comprehensive data suggesting that low-frequency variants
      encoding possible functional amino acid polymorphisms in the HMCN1 gene may not
      contribute substantially to disease, although HMCN1 mutations may still confer
      disease susceptibility in a small subset of patients. Interestingly, the HMCN1
      p.Gln5346Arg mutation, which is thought to be a causal mutation in a large AMD
      pedigree segregating the disease as a single-gene trait, appears to occur in our
      control cohort as a low-frequency polymorphism with an allele frequency of
      approximately 0.0026.

PMID- 17216617
TI  - Lower limb nerve injuries in children.
AB  - The aim of this paper is to emphasize the seriousness of pediatric peripheral
      nerve injuries of lower limbs and to stress the importance of early exploration
      of the injured nervous trunk in order to reduce the number of unfavorable
      outcomes. Among 136 traumatic peripheral nerve injuries in the children we
      treated, 31 nerve injuries of the lower limbs were observed. Causes of injury and
      time to recovery were evaluated. The sciatic nerve was involved in 19 cases,
      peroneal nerve in 11, root avulsions of the spinal cord in 1. We observed
      complete recovery in 12 cases and incomplete or no recovery at all in 19. The
      mean time to recovery in patients who underwent surgery was 18 months (range: 1
      32). Considering the rate of spontaneous recovery of postinjection nerve injuries
      of the sciatic nerve and early onset of skeletal deformities, a closed nerve
      injury of the lower limb with no recovery within 3 months should always undergo
      surgery, even if complete functional outcome is not always guaranteed.

PMID- 17216618
TI  - Allelic variants in HOX genes in cryptorchidism.
AB  - BACKGROUND: Cryptorchidism is one of the most common congenital anomalies and is
      associated with increased risk for infertility and testicular cancer later in
      life. Findings from animal models and small clinical studies suggest that the
      posterior HOX genes (paralogs 9-13) could be potential candidate genes for
      cryptorchidism and that the HOX genes are functionally redundant within
      paralogous groups. METHODS: The coding regions and exon-intron boundaries of the
      16 posterior HOX genes were sequenced and analyzed in group 1 (44 nonsyndromic
      cryptorchidism cases and 46 healthy controls). Those specific variants found to
      be significantly different between cases and controls in group 1 were examined in
      DNA from group 2 (108 cases and 114 controls). RESULTS: A total of 57 variants
      was found in group 1, among which the allele frequency of 180A>G (A60A) in HOXD13
      alone was significantly elevated in cases versus controls (P = 0.02). In the
      combined 1 + 2 group, cases were also more likely than controls to have the G
      allele (P = 0.002). As predicted by an exonic splicing enhancer finder program,
      the 180A>G (A60A) variant is expected to have an influence on the splicing of
      transcripts from HOXD13. In group 1, case subjects were more likely to carry
      multiple variants in HOXA13 and HOXD13 (P = 0.02) than controls. CONCLUSIONS: The
      variant 180A>G (A60A) in HOXD13 is a risk factor for cryptorchidism, and a
      dynamic equilibrium of genes in HOX paralog 13 is involved in the pathogenesis of
      cryptorchidism.

PMID- 17216619
TI  - Long-term grooming partnerships between unrelated adult females in a free-ranging
      group of Japanese monkeys (Macaca fuscata).
AB  - In order to examine the presence of long-term grooming relationships among
      unrelated females, grooming interactions of 18 adult females (range: 16-32 years)
      in a free-ranging group of Japanese monkeys (Macaca fuscata) were recorded in
      2003 and compared with those recorded 10 years earlier, i.e., in 1993. In 2003,
      on average, each female who had survived the 10 years had grooming interactions
      with 2.2 surviving old partners with whom she was recorded to have grooming
      interactions in 1993, 3.5 females related to the surviving old partners, and 4.5
      unrelated females who were other than the surviving old partners or their related
      females. By calculating the ratio of actual grooming partners to available
      females in 2003, we concluded that females had a greater possibility of selecting
      surviving old partners as their grooming partners than other unrelated partners,
      and that they also had a greater possibility of selecting females related to
      surviving old partners than females other than surviving old partners and their
      related females. These findings indicate that with regard to grooming
      relationships, female Japanese monkeys are basically conservative, showing a
      tendency to concentrate their grooming interactions on closely related females
      and certain familiar unrelated females such as surviving old partners and some
      females closely related to these partners. At the same time, however, female
      Japanese monkeys also showed a progressive trait for grooming since they formed
      grooming relationships with new partners. The necessity of long-term
      psychological bonding for long-term grooming relationships between unrelated
      females is discussed in this work.

PMID- 17216620
TI  - Early predictors of self-biting in socially-housed rhesus macaques (Macaca
      mulatta).
AB  - The development of self-biting behavior in captive monkeys is little understood
      and poses a serious risk to their well-being. Although early rearing conditions
      may influence the expression of this behavior, not all animals reared under
      similar conditions self-bite. The purpose of this study was to examine the
      effects of three rearing conditions on biting behavior and to determine whether
      early infant behavior can predict later self-biting. The subjects were 370 rhesus
      macaques born at the National Institutes of Health (NIH) Animal Center between
      1994 and 2004. They were reared under three conditions: mother-reared in social
      groups (n=183), peer-reared in groups of four (n=84), and surrogate-peer-reared
      (n=103). Significantly more surrogate-peer-reared animals self-bit compared to
      peer-only or mother-reared animals. There was no sex difference in self-biting,
      but this result may have been affected by a sex bias in the number of
      observations. The durations of behaviors exhibited by the surrogate-peer-reared
      subjects were recorded in 5-min sessions twice a week from 2 to 6 months of age
      while the animals were in their home cages and play groups. In the play-group
      situation, surrogate-peer-reared subjects who later self-bit were found to be
      less social and exhibited less social clinging than those that did not self-bite.
      Home-cage behavior did not predict later self-biting, but it did change with
      increasing age: surrogate clinging and self-mouthing decreased, while
      environmental exploration increased. Our findings suggest that surrogate rearing
      in combination with lower levels of social contact during play may be risk
      factors for the later development of self-biting behavior.

PMID- 17216622
TI  - Response toward novel stimuli in a group of tufted capuchins (Cebus libidinosus)
      in Brasilia National Park, Brazil.
AB  - We investigated responses toward novel foods and novel objects by wild capuchins
      that routinely exploit visitors' foods in Brasilia National Park. Given the
      capuchins' daily exposure to human foods and objects, we expected them to be more
      explorative toward novel foods and objects compared to capuchins that are not
      habituated to visitors. However, since the safety and palatability of potential
      foods have to be learned, we also expected the capuchins to be cautious about
      eating novel foods, as has been reported for wild and captive capuchins. Stimuli
      were presented on a platform in four experimental conditions: familiar food (FF),
      novel food (NF), familiar food plus novel object (FF+O), and novel food plus
      novel object (NF+O). Latencies to approach and contact the platform, and to
      approach and to ingest food did not differ across conditions. Nevertheless, the
      capuchins were significantly more responsive (measured in terms of interest,
      manipulation, etc.) toward familiar foods than novel foods, and ate significantly
      more of the former. In other words, their explorative response toward novel foods
      led to little consumption. Our results do not support the "readiness to eat"
      hypothesis, according to which a lower readiness to eat and food neophobia are
      the consequences of the presence of a distracting novel object. The finding that
      capuchins explore novel stimuli but remain cautious about eating novel foods
      supports the view that neophilia and neophobia are motivationally independent
      responses.

PMID- 17216623
TI  - Platelet microparticles are heterogeneous and highly dependent on the activation
      mechanism: studies using a new digital flow cytometer.
AB  - BACKGROUND: Platelet-derived microparticles (MPs) are believed to play an
      important role in coagulation and inflammatory disorders. Unfortunately, MP size
      renders them difficult to study and analyze by conventional flow cytometry.
      METHODS: We analyzed and characterized platelet-derived MPs, using antibodies
      against the major surface glycoproteins (GP), the platelet activation antigen P
      selectin (CD62P), and a marker of procoagulant activity (phosphatidylserine
      exposure). MPs were generated by exposure of platelets to thrombin receptor
      activating peptide (TRAP) or ionophore. Both agonists induced significant
      microvesiculation of platelets, and the resulting MPs were analyzed by a new
      digital flow cytometer: Becton-Dickinson FACSAria. RESULTS: Membrane GPs were
      equally well represented in MPs generated by either reagent. In contrast, P
      selectin was more intensely expressed in TRAP-MPs, while phosphatidylserine (PS)
      expression was markedly increased in ionophore-MPs. Two distinct populations of
      TRAP-MPs (one PS-positive and another PS-negative) were apparent. The latter
      characteristic facilitated sorting of MPs according to their PS exposure.
      CONCLUSIONS: The data presented herein show a significant improvement in the
      methodology applied until now to the characterization of MPs. The ability to
      characterize and sort MP subpopulations may help to resolve their contributions
      to normal and pathological functions.

PMID- 17216624
TI  - Maternal use of selective serotonin re-uptake inhibitors in early pregnancy and
      infant congenital malformations.
AB  - BACKGROUND: Maternal use of selective serotonin re-uptake inhibitors (SSRIs) has
      recently been associated with an increased risk for certain malformations.
      METHODS: Using the Swedish Medical Birth Register, we identified women who had
      reported the use of SSRIs in early pregnancy and studied their infants, born
      between July 1, 1995 and the end of 2004. Congenital malformations were
      identified from that register, from the Register of Congenital Malformations, and
      from the Hospital Discharge Register. The effect of drug exposure was studied
      after adjustment for a number of identified maternal characteristics that could
      act as confounders. RESULTS: We identified 6,481 women who reported the use of
      SSRIs in early pregnancy and their 6,555 infants. There was no general increase
      in malformation risk. An increased risk for cystic kidneys was seen, but this was
      based on only nine malformed infants, and the pathology varied between these
      cases. An in-depth study of cardiovascular defects identified an association
      between such defects and notably ventricular and atrial septum defects and
      maternal use of paroxetine but not other SSRIs. No support for a postulated
      association between SSRI use and infant craniostenosis or omphalocele was found.
      CONCLUSIONS: Use of SSRIs in early pregnancy does not seem to be a major risk
      factor for infant malformations. The association between paroxetine use and
      infant cardiovascular defects may be a result of multiple testing, but is
      supported by other studies.

PMID- 17216625
TI  - Maternal flu or fever, medication use, and neural tube defects: a population
      based case-control study in Northern China.
AB  - BACKGROUND: Maternal exposure to flu or fever has been associated with increased
      risk for neural tube defects (NTDs); however, few studies have considered the
      effects of medications on the effects of flu or fever. We evaluated the effect of
      maternal flu or fever, medication use (antibiotics, antipyretics), and their
      joint effect on NTDs. METHODS: Data came from an ongoing population-based case
      control study of infants with external malformations in northern China. The case
      group included 363 infants with NTDs identified between January 2003 and June
      2005. Controls were 523 newborn infants without identified congenital anomalies
      matched by county, sex, maternal ethnic group, and the closest date of conception
      for infants with any major external malformation. Data were collected by a
      trained health worker through face-to-face interviews after delivery. RESULTS:
      NTD risks were significantly associated with maternal flu or fever (adjusted odds
      ratio [AOR] = 3.93, 95% CI: 2.48-6.23) and antipyretic use (AOR = 4.86, 95% CI:
      1.33-17.78), but not with antibiotic use (AOR = 1.75, 95% CI: 0.91-3.38) after
      adjusting for potential confounders. NTD risk associated with maternal
      antipyretic use was markedly higher for anencephaly (AOR = 7.03, 95% CI: 1.70
      29.04) than for spina bifida (AOR = 3.98, 95% CI: 0.95-16.74). Mothers with flu
      or fever who were also using antipyretics showed a markedly higher AOR for
      anencephaly (14.75 vs. 4.52), spina bifida (16.30 vs. 3.85), and all NTDs
      combined (13.91 vs. 4.04) than mothers with flu or fever who were not using
      antipyretics. Maternal antibiotics did not markedly change the effects of flu or
      fever on anencephaly (4.17 vs. 4.83), spina bifida (5.08 vs. 4.21), and all NTDs
      combined (5.05 vs. 4.29). CONCLUSIONS: Maternal flu or fever and antipyretic use
      during the periconceptional period increases the risk for NTDs. Maternal exposure
      to antipyretics together with flu or fever results in a markedly higher risk of
      NTDs than exposure to flu or fever alone.

PMID- 17216626
TI  - Plant DNA sequences from feces: potential means for assessing diets of wild
      primates.
AB  - Analyses of plant DNA in feces provides a promising, yet largely unexplored,
      means of documenting the diets of elusive primates. Here we demonstrate the
      promise and pitfalls of this approach using DNA extracted from fecal samples of
      wild western gorillas (Gorilla gorilla) and black and white colobus monkeys
      (Colobus guereza). From these DNA extracts we amplified, cloned, and sequenced
      small segments of chloroplast DNA (part of the rbcL gene) and plant nuclear DNA
      (ITS-2). The obtained sequences were compared to sequences generated from known
      plant samples and to those in GenBank to identify plant taxa in the feces. With
      further optimization, this method could provide a basic evaluation of minimum
      primate dietary diversity even when knowledge of local flora is limited. This
      approach may find application in studies characterizing the diets of poorly
      known, unhabituated primate species or assaying consumer-resource relationships
      in an ecosystem.

PMID- 17216627
TI  - Measurement of eye-gaze in chimpanzees (Pan troglodytes).
AB  - Gaze cues are used as an index of social cognition in primates, yet the
      sensitivity to different forms of gaze, and consequently the cues required to
      test gaze-following abilities remain understudied. Whereas the eye is attributed
      special signal value in humans, the camouflaged ocular morphology of non-human
      primates has led to the consensus that head orientation may be a more salient
      cue. This study presents the first documentation of the surface eye movements of
      the chimpanzee, Pan troglodytes, in order to determine the behavioral forms of
      eye-gaze and their saliency as signals, document their functional variation, and
      address the signal value of the eyes distinct from head orientation. Movements of
      the eye were identified as Scan (continuous movement), Glance (a single movement
      <1 sec), or Fixate (no movement). Scans, glances, and fixations were reliably
      detected by humans during live observation and from video (Cohen's kappa over
      0.70) and, therefore, are likely also to be detected by conspecifics. Eye-gaze
      comprised a nonunitary measure of visual attention, reflecting the attentional
      task demands of different activities. Specifically, chimpanzees spent
      significantly more time scanning while feeding and resting, than grooming,
      F(2,28) = 10.23, P<0.001, and spent significantly more time fixating while
      grooming, than feeding or resting, F(2,28) = 7.52, P<0.01. Further, eye-gaze was
      often incongruent with head movement, varying significantly with the form of eye
      gaze: incongruence was found during 12-21% of fixations, during 42-49% of scans,
      and during 70-100% of glances, F(2,16) = 30.17, P<0.001. These findings provide
      the basis for discrimination of the adaptive significance of gaze-processing
      abilities with emphasis on sensitivity to eye-gaze distinct from head
      orientation. If we are to continue exploring gaze-processing abilities in
      primates, then we need greater consideration of the precise nature of the signals
      themselves. Here we present evidence for special consideration of the eyes as a
      salient signal in P. troglodytes.

PMID- 17216628
TI  - RE: Secret ties to industry and conflicting interests in cancer research.

PMID- 17216629
TI  - Titan's ion chemistry: a laboratory perspective.
AB  - Some of the most interesting objects in the solar system are those bodies that
      have significant atmospheres. The discovery that Titan, Saturn's largest
      satellite, has a substantial nitrogen-based atmosphere makes it a prime
      extraterrestrial object of interest. The advent of the Cassini orbiter spacecraft
      program that is able to observe and sample Titan's ionosphere adds greatly to
      this interest. We report here a summary of some of the efforts that have been
      made in the laboratory to understand the processes responsible for chemical
      processing of the primary ions formed in Titan's ionosphere, into the ions
      observed by in situ sampling. The presence of significant hydrocarbons and the
      colder temperatures of Titan's ionosphere lead to a much greater complexity in
      the ion chemistry of Titan than is apparent in the ion chemistry of Earth. A
      review of all the ion-molecule chemistry investigated in laboratory studies
      relevant to Titan is included as a table. The complexity of some of the
      hydrocarbon ion structures formed in just three reactive ion-molecule sequences
      from the primary ions has required a new experimental methodology which is
      discussed.

PMID- 17216630
TI  - The economic burden of carpal tunnel syndrome: long-term earnings of CTS
      claimants in Washington State.
AB  - BACKGROUND: The long-term earnings losses borne by injured workers, beyond those
      covered by workers' compensation insurance, are rarely estimated. The post-claim
      earnings of a cohort of carpal tunnel syndrome (CTS) claimants are tracked over a
      period of 6 years and compared to the earnings of claimants with either upper
      extremity fractures or dermatitis. METHODS: Quarterly earnings records of 4,443
      workers in Washington State who filed claims with the State Fund in 1993 or 1994
      for CTS are compared to those of 2,544 with upper-extremity fracture claims and
      1,773 with medical-only dermatitis claims. Multivariate regression was used to
      identify the effect of injury type on earnings from that of other potential
      predictors. RESULTS: CTS claimants recover to about half of their pre-injury
      earnings level relative to that of comparison groups after 6 years; they also
      endured periods on time-loss three times longer than claimants with upper
      extremity fractures. CTS surgery claimants had better outcomes than those who did
      not have surgery. Earnings recovery fractions among CTS claimants were better for
      workers who: (1) were younger; (2) had stable pre-claim employment; (3) lived in
      the Puget sound area; (4) worked for large businesses; (5) worked in non
      construction/transportation industries; or (6) were in the higher pre-injury
      earnings categories. Cumulative excess loss of earnings of the 4,443 CTS
      claimants was 197 million dollars to 382 million dollars over 6 years, a loss of
      45,000-89,000 dollars per claimant. This underscores the importance of
      prevention, early diagnosis, and accommodation for return to work.

PMID- 17216631
TI  - One-dimensional self-assembly of a rational designed beta-structure peptide.
AB  - Fabricating various nanostructures based on the self-assembly of diverse
      biological molecules is now of great interest to the field of bionanotechnology.
      In this study, we report a de novo designed peptide (T1) with a preferential beta
      hairpin forming property that can spontaneously assemble into nanofibrils in
      ultrapure water. The nanofibrils assembled by T1 could grow up to tens of microns
      in length with a left-handed helical twist and an average height of 4.9 +/- 0.9
      nm. Moreover, protofilaments and nucleus structures both with a similar height of
      1.4 +/- 0.2 nm were observed during fibrilization as well as via sonication of
      the mature nanofibrils. A typical conformational transition from random coil to
      beta-structure was observed in association with the fibrilization. Molecular
      modeling of T1 assemblies displayed that the beta-hairpin molecules organize in a
      parallel fashion in which the beta-strands align in an antiparallel fashion and
      each adjoining beta-strand runs left-handed twist at about 2.9 degrees with
      respect to the one located before it along the fibrillar axis. It also revealed
      that the maximum thickness of the assembly intermediate, the helical tape
      structure, is about 1.4 nm and four tapes can further assemble into a fibril with
      a diameter of about 4.1 nm. Taken together the results obtained by AFM, CD, and
      molecular modeling, T1 fibrilization probably undergoes a hierarchy approach, in
      which the aromatic stacking and the electrostatic interactions between the
      assembled structures are most likely the two major factors directing the one
      dimensional self-assembly. Based on these studies, we propose T1 can be used as a
      model peptide to investigate the beta-sheet based self-assembly process and could
      be a potential bioorganic template to develop functional materials.

PMID- 17216632
TI  - Fmoc-based solid-phase synthesis of GPR54-agonistic pentapeptide derivatives
      containing alkene- and fluoroalkene-dipeptide isosteres.
AB  - Fmoc-protected Phe-Gly-type (Z)-alkene dipeptide isostere (ADI) and (E)
      fluoroalkene dipeptide isostere (FADI) were synthesized and applied to Fmoc-based
      solid-phase peptide synthesis (SPPS). These cis-peptide bond mimetics were
      introduced into a bioactive pentapeptide [H-Amb-Phe-Gly-Leu-Arg-Trp-NH(2); Amb =
      4-(aminomethyl) benzoic acid], which has potent GPR54 agonistic activity. The
      resulting pentapeptide derivatives showed low GPR54 agonistic activity, as
      compared with the parent peptide and (E)-ADI-containing derivative. This suggests
      that the trans-amide conformer of Phe-Gly peptide bond of the parent peptide
      would be significantly important for bioactivity. Contrary to our expectations, a
      (Z)-FADI-containing derivative exhibited essentially no activity, revealing the
      necessity of critical validation of FADI-bioisosterism.

PMID- 17216634
TI  - Leucyl/phenylalanyl(L/F)-tRNA-protein transferase-mediated aminoacyl transfer of
      a nonnatural amino acid to the N-terminus of peptides and proteins and subsequent
      functionalization by bioorthogonal reactions.
AB  - We report here a new strategy for derivatizing peptides and proteins at the N
      terminus. To achieve this, a nonnatural amino acid was charged onto a tRNA and
      then enzymatically transferred to a lysine (Lys) unit at the N-terminus of a
      peptide or a protein by using L/F-tRNA-protein transferase. By using the
      chemoenzymatic technique, beta-(2-quinolyl)-L-alanine, p-azido-L-phenylalanine,
      and p-acetyl-L-phenylalanine were introduced to the N-terminus. The latter two
      nonnatural amino acids possess bioorthogonal functional groups to which
      artificial tags can be introduced. Actually, a biotin tag was coupled to the
      bioorthogonal ketone group of acetylphenylalanine at the N-terminus of a peptide.
      N-terminal-specific biotinylation and fluorescence derivatization of the
      bioorthogonal azido-containing protein or peptide was also carried out based on a
      [3 + 2] cycloaddition. The enzymatic transfer of a nonnatural amino acid to the N
      terminus of target peptides or proteins was also successfully achieved in the
      presence of other peptides or crude protein mixtures.

PMID- 17216635
TI  - Structure-activity relationship of HP (2-20) analog peptide: enhanced
      antimicrobial activity by N-terminal random coil region deletion.
AB  - HP (2-20) (AKKVFKRLEKLFSKIQNDK) is a 19-aa antimicrobial peptide derived from N
      terminus of Helicobacter pylori Ribosomal protein L1 (RpL1). In the previous
      study, several analogs with amino acid substitutions were designed to increase or
      decrease only the net hydrophobicity. In particular, substitutions of Gln(16) and
      Asp(18) with Trp (Anal 3) for hydrophobic amino acid caused a dramatic increase
      in antibiotic activity without a hemolytic effect. HP-A3 is a potent
      antimicrobial peptide that forms, in a hydrophobic medium, an amphipathic
      structure consisting of an N-terminal random coil region (residues 2-5) and
      extended C-terminal regular alpha-helical region (residues 6-20). To obtain the
      short and potent alpha-helical antimicrobial peptide, we synthesized a N-terminal
      random coil deleted HP-A3 (A3-NT) and examined their antimicrobial activity and
      mechanism of action. The resulting 15mer peptide showed increased antibacterial
      and antifungal activity to 2- and 4-fold, respectively, without hemolysis.
      Confocal fluorescence microscopy studies showed that A3-NT was accumulated in the
      plasma membrane. Flow cytometric analysis revealed that A3-NT acted in salt- and
      energy-independent manner. Furthermore, A3-NT causes significant morphological
      alterations of the bacterial surfaces as shown by scanning electron microscopy.
      Circular dichroism (CD) analysis revealed that A3-NT showed higher alpha-helical
      contents than the HP-A3 peptide in 50% TFE solution. Therefore, the cell-lytic
      efficiency of HP-A3, which depended on the alpha-helical content of peptide,
      correlated linearly with their antimicrobial potency.

PMID- 17216636
TI  - Slow tert-butyl ester acidolysis and peptide 3(10)-helix to alpha-helix
      transition in HFIP solution.
AB  - We have already shown by CD and NMR techniques that the terminally protected homo
      octapeptides Z (and Ac)-[L-(alphaMe)Val](8)-OtBu undergo a slow and irreversible
      3(10)-helix to alpha-helix transition when dissolved in 1,1,1,3,3,3
      hexafluoroisopropanol. In the present work, we find by HPLC and CD that under the
      aforementioned experimental conditions, a slow acidolysis of the tert-butyl ester
      functionality does take place affording the corresponding octapeptide free acids.
      The results of our combined chromatographic and spectroscopic experiments are
      confirmed by a comparison with the properties of independently synthesized and
      chemically characterized authentic compounds.

PMID- 17216637
TI  - Predictors of weight loss in Parkinson's disease: is weight loss the chicken or
      the egg?

PMID- 17216638
TI  - Methods of evaluation of musician's dystonia: critique of measurement tools.
AB  - Musician's dystonia is associated with significant morbidity. To assess treatment
      options, accurate and precise measurements of disease severity are critical. We
      describe current methods of quantitatively measuring musician's dystonia of the
      upper extremity including subjective, objective, and automated methods. The
      degree to which these methods satisfy rigorous measurement criteria, including
      their reliability, validity, responsiveness to treatment, and practicality, is
      examined. We report that most of these methods have not been properly evaluated.
      Therefore, treatment trials based on these methods are difficult to interpret.

PMID- 17216639
TI  - Pathogenicity of the Lrrk2 R1514Q substitution in Parkinson's disease.
AB  - An increasing number of nonsynonymous LRRK2 variants are being reported as
      putative pathogenic mutations. We identified one large kindred harboring the
      Lrrk2 R1514Q substitution; however, the variant did not segregate fully with
      disease. Combined analyses of three case-control series demonstrate that the
      R1514Q substitution is not associated with increased risk of disease (OR: 1.3;
      95% CI: 0.6-2.8; P = 0.45). These findings highlight the importance of using
      family-based studies and multiple population screenings when examining the
      association of these polymorphic LRRK2 gene variants with Parkinson's disease.

PMID- 17216640
TI  - Quality of life in focal, segmental, and generalized dystonia.
AB  - The objective of this study was to assess quality of life (QoL) in a community
      based sample of people with various forms of dystonia and to identify the factors
      that predict QoL in dystonia. QoL was assessed using two generic questionnaires:
      the Medical Outcomes Study Short-Form 36 (SF36) and the EuroQol questionnaire. A
      host of demographic, clinical, and psychosocial variables were measured to
      identify the best predictors of QoL in dystonia. A comparison of EuroQol and SF36
      scores with the norms for the general UK population of similar age showed that
      people with dystonia had scores indicative of worse QoL on all domains,
      particularly those related to physical and social functioning. The impairment of
      QoL was seen in all age groups and was similar for men and women. Compared to the
      focal dystonia group, participants with generalized dystonia scored significantly
      worse on all QoL measures. Participants who were unemployed also scored
      significantly worse. There was also a trend for younger and separated/divorced
      participants to score worse on QoL measures. A stepwise regression analysis
      revealed that functional disability, body concept, and depression were important
      predictors of QoL in dystonia. Dystonia influences various aspects of QoL,
      particularly those related to physical and social functioning. The impairment of
      QoL was greater for participants with generalized dystonia, those who were
      unemployed, younger, and separated/divorced. Functional disability, body concept,
      and depression were the best predictors of QoL in dystonia. Efforts to improve
      health care for people with dystonia should not only focus on management of the
      movement disorder but also consider modifying functional disability and negative
      body concept and depression that contribute to poor QoL in this disorder.

PMID- 17216641
TI  - Unilateral versus bilateral tasks in early asymmetric Parkinson's disease:
      differential effects on bradykinesia.
AB  - Patients with Parkinson's disease (PD) have an impaired ability to perform two
      different simultaneous bimanual tasks. The differential effects of unilateral
      versus bilateral identical tasks on the bradykinesia scores of the more and less
      affected limbs in PD have not been examined. Twenty-seven patients with early and
      asymmetric PD underwent blinded, videotaped assessment, independently for each
      limb, using the bradykinesia items of the Unified Parkinson's Disease Rating Part
      III, Motor subscale (mUPDRS) and a Modified Bradykinesia Rating Scale (MBRS),
      which assessed amplitude, speed, and rhythm of movements. We found that the score
      for finger tapping in mUPDRS and MBRS, the score of amplitude of finger tapping
      in MBRS, and the lateralized scores of mUPDRS (sum of Items 23 to 25) of the most
      affected side significantly improved during the bimanual task. The improvement
      was associated with longer duration of illness, higher total scores in mUPDRS,
      and higher lateralized bradykinesia scores of the most affected side. There was a
      simultaneous deterioration of the lateralized bradykinesia scores in MBRS (sum of
      Items 23 to 25) and Item 25 of mUPDRS (rapid alternating movements) of the least
      affected side in bimanual tasks. In conclusion, identical bimanual tasks
      facilitate movement of the most affected side in early asymmetric PD at the cost
      of motor degradation in the least affected side. This observation also highlights
      the need to perform tasks of bradykinesia in one limb at a time for best
      accuracy.

PMID- 17216642
TI  - Lower stimulation frequency can enhance tolerability and efficacy of pallidal
      deep brain stimulation for dystonia.
AB  - We report the case of a patient with medically refractory primary dystonia who
      was treated with bilateral pallidal deep brain stimulation. Stimulation at 130 Hz
      or higher, by means of the more ventral contacts generated capsular side effects,
      which made their use impractical. Consequently, the patient was treated for 9
      months at 130 to 185 Hz, by means of the more dorsal contacts, achieving modest
      results. By reducing the stimulation frequency to 80 Hz, we were able to activate
      the ventral contacts without inducing side effects. Within days, the patient
      experienced a dramatic improvement in function that has persisted for 1 year. A
      further reduction in stimulation frequency to 60 Hz resulted in a worsening of
      his symptoms. We conclude that chronic stimulation at frequencies of <100 Hz may
      be efficacious in dystonia and may enhance the tolerability of stimulation by
      means of contacts that are positioned posteroventrally within the internal globus
      pallidus, nearer the internal capsule.

PMID- 17216643
TI  - Rett syndrome: an overlooked diagnosis in women with stereotypic hand movements,
      psychomotor retardation, Parkinsonism, and dystonia?
AB  - Rett syndrome is an X-linked neurodevelopmental disorder resulting in profound
      psychomotor retardation. It is usually diagnosed by a pediatrician or pediatric
      neurologist. Adult neurologists may, therefore, overlook the possibility of Rett
      syndrome in women with psychomotor retardation of unknown etiology. We report the
      case of a woman diagnosed with Rett syndrome at age 49 years. This report
      emphasizes the diagnostic value of movement disorders, including hand
      stereotypies, Parkinsonism, and dystonia, in adults with Rett syndrome.

PMID- 17216644
TI  - Treatable fluctuating Parkinsonism and dementia in a patient with a dural
      arteriovenous fistula.

PMID- 17216646
TI  - Autoimmune thyroid disease and segmental myoclonus.

PMID- 17216647
TI  - Intramedullary spinal tumor causing "belly dancer syndrome".

PMID- 17216648
TI  - Gait abnormalities in psychogenic movement disorders.
AB  - An abnormal gait is not uncommon in patients with medically unexplained
      neurological symptoms, including those with other psychogenic movement disorders
      (PMDs). Previous studies have not evaluated the gait characteristics of patients
      with a variety of PMDs and there are no reports comparing PMDs with and without
      gait disturbances. We were interested in determining how those with and without
      additional involvement of gait differed and how PMD patients differed from those
      with a pure psychogenic gait disorder (PGD) in the absence of another PMD. We
      investigated gait features in a large series of patients with PMD (n = 279),
      dividing them into two groups (Group I with a normal gait and Group II with an
      abnormal gait). Group I included those with PMD with a normal gait and no change
      in the PMD while walking (I-1), and those with a change in PMD while walking, but
      not affecting gait (I-2). Group II was divided into those with PMD with
      additional abnormal gait (II-1) and those with pure psychogenic gait disorder
      without other abnormal movements (II-2). Excessive slowing of movement was more
      common in PMD patients with an abnormal gait (Group II) compared to those without
      (Group I). Slowness of gait was the most common feature in patients with PMD
      combined with a PGD (II-1) and buckling of the knee pattern was the most common
      type of pure PGD (II-2), followed by astasia-abasia.

PMID- 17216649
TI  - Local field potentials and oscillatory activity of the internal globus pallidus
      in myoclonus-dystonia.
AB  - The pathophysiology of myoclonus-dystonia (M-D), an autosomal dominantly
      inherited movement disorder characterized by myoclonic jerks and dystonic
      contractions, is largely unknown. In the present study, local field potential
      (LFP) activities in the globus pallidus internus (GPi) from two genetically
      proven M-D patients are investigated. Coherence analysis between GPi LFP activity
      and electromyographic muscle activity (EMG) and synchronization of GPi neuronal
      activity using event-related spectral perturbation (ERSP) in a go-no-go paradigm
      were studied. Significant increased coherence in the 3 to 15 Hz frequency band
      was detected between GPi LFP activity and several muscles, with the LFP leading
      the muscles. The ERSP analysis revealed synchronization in the 3 to 15 Hz
      frequency band within the GPi before the imperative cue of the go-no-go task and
      desynchronization in the same band after the cue. The LFP recordings of the GPi
      in M-D show that the low-frequency band previously described in dystonia is also
      involved in the dystonia plus syndrome M-D. The 3 to 15 Hz synchronization in the
      go-no-go paradigm has not been described previously and may point to the
      existence of (myoclonus-)dystonia specific oscillatory activity in the GPi.

PMID- 17216650
TI  - Sporadic case of spinocerebellar ataxia type 17: treatment observations for
      managing urinary and psychotic symptoms.

PMID- 17216651
TI  - Carbidopa/levodopa-responsive myoclonus.
AB  - A 64-year-old right-handed woman's right hand and arm developed spontaneous jerks
      that eventually involved her trunk. As she had some features of parkinsonism, she
      was treated with carbidopa/levodopa and her myoclonus dramatically improved. The
      mechanism accounting for this improvement is unknown.

PMID- 17216652
TI  - Magnetic resonance spectroscopic evidence for presupplementary motor area
      neuronal dysfunction in Parkinson's disease.
AB  - The anterior cingulate (AC) gyrus and the presupplementary motor area (pre-SMA)
      show pathological changes in Parkinson's disease (PD). We examined if PD patients
      show magnetic resonance spectroscopy (MRS) changes in NAA/Cr in the AC, pre-SMA,
      or posterior cingulate (PC). Forty-four (27 male, 17 female) healthy nondemented
      PD patients and 38 controls (18 male, 20 female) 65 years of age and older were
      examined using the Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental
      State Examination, Frontal Assessment Battery, and Geriatric Depression Scale.
      MRS was performed at 1.5 T. Voxels (8 cc; PRESS; TE = 80; TR = 1,600 ms) were
      placed mid-sagittally. Gray matter and white matter volumes were measured within
      voxels using SPM2. Spectra were analyzed using LC model to yield NAA/Cr and
      Cho/Cr. Demographic and cognitive measures did not differ between groups. Motor
      UPDRS was 17.7 +/- 8.8 for PD. Pre-SMA NAA/Cr was lower in PD (PD: 1.39 +/- 0.17;
      control: 1.47 +/- 0.16; P = 0.045) and correlated negatively with age (r = 0.39;
      P = 0.01), but not with UPDRS, disease duration, or dopamine equivalents. AC and
      PC NAA/Cr and Cho/Cr in any region did not differ (P > 0.05). In conclusion, pre
      SMA NAA/Cr was selectively decreased in PD, consistent with neuronal dysfunction.
      This should be further examined as a biomarker of disease in PD.

PMID- 17216653
TI  - Rapid responses of ribosomal RNA synthesis to nutrient shifts.
AB  - A major challenge in systems biology is to integrate our mechanistic
      understanding of gene regulation to predict quantitatively how cells will respond
      to environmental changes. Living cells respond rapidly to the availability of
      nutrients in part by altering production of ribosomal RNA (rRNA), a limiting
      component in the biosynthesis of ribosomes. Studies of rRNA transcription by the
      RNA polymerase of Escherichia coli have identified regulatory roles for guanosine
      tetraphosphate (ppGpp), the initiating nucleotide, and the protein DksA. To what
      extent findings from in vitro studies can be used to quantitatively predict in
      vivo responses to changing nutrient environments is unknown. We developed a
      mechanistic mathematical model for rRNA transcriptional responses to such
      changes. Our model accounts for binding of RNAP to its rRNA promoter to form a
      closed complex, isomerization from a closed complex to an open complex,
      reversible incorporation of the initiating NTP (iNTP), transcript elongation, and
      clearance of the promoter. Further, the model incorporates interactions between
      ppGpp and DksA with transcription intermediates, and it includes an empirical
      correction to account for salt effects. The model biophysical parameters were
      determined using 33 single- and multi-round transcription experiments spanning
      487 in vitro measurements. By incorporating in vivo measurements of ppGpp and
      ATP, the model correctly predicted rRNA production rates for cellular responses
      to nutrient upshifts, downshifts, and outgrowth into fresh medium. Inclusion of
      DksA was essential in all three cases. Our work provides a foundation for using
      data-driven computational models to predict the kinetics of in vivo
      transcriptional responses.

PMID- 17216654
TI  - Comparisons of optical pH and dissolved oxygen sensors with traditional
      electrochemical probes during mammalian cell culture.
AB  - Small-scale upstream bioprocess development often occurs in flasks and multi-well
      plates. These culturing platforms are often not equipped to accurately monitor
      and control critical process parameters; thus they may not yield conditions
      representative of manufacturing. In response, we and others have developed
      optical sensors that enable small-scale process monitoring. Here we have compared
      two parameters critical to control in industrial cell culture, pH and dissolved
      oxygen (DO), measured with our optical sensors versus industrially accepted
      electrochemical probes. For both optical sensors, agreement with the
      corresponding electrochemical probe was excellent. The Pearson Correlations
      between the optical sensors and electrochemical probes were 98.7% and 99.7%, for
      DO and pH, respectively. Also, we have compared optical pH sensor performance in
      regular (320 mOsm/kg) and high-osmolality (450 mOsm/kg) cell culture media to
      simulate the increase in osmolality in pH-controlled cultures. Over a pH range of
      6.38-7.98 the average difference in pH readings in the two media was 0.04 pH
      units. In summary, we have demonstrated that these optical sensors agree well
      with standard electrochemical probes. The accuracy of the optical probes
      demonstrates their ability to detect potential parameter drift that could have
      significant impact on growth, production kinetics, and protein product quality.
      We have also shown that an increase in osmolality that could result from
      controlling pH or operating the reactor in fed-batch mode has an insignificant
      impact on the functionality of the pH patches.

PMID- 17216655
TI  - Effect of wall shear rate on biofilm deposition and grazing in drinking water
      flow chambers.
AB  - The effect of four-wall shear rates (34.9, 74.8, 142.5, and 194.5 s(-1)) on
      bacterial deposition on glass slides in drinking water flow chambers was studied.
      Biofilm image acquisition was performed over a 50-day period. Bacterial
      accumulation and surface coverage curves were obtained. Microscopic observations
      allowed us to obtain information about the dynamics and spatial distribution of
      the biofilm. During the first stage of biofilm formation (210-518 h), bacterial
      accumulation was a function of the wall shear rate: the higher the wall shear
      rate, the faster the bacterial deposition (1.1 and 1.9 x 10(4) bacterial cells .
      cm(-2) for wall shear rates of 34.9 and 142.5 s(-1), respectively). A new
      similarity relationship characteristic of a non-dimensional time and function of
      the wall shear rate was proposed to describe initial bacterial deposition. After
      50 days of exposure to drinking water, surface coverage was more or less
      identical under the entire wall shear rates (7.44 +/- 0.9%), suggesting that
      biofilm bacterial density cannot be controlled using hydrodynamics. However, the
      spatial distribution of the biofilm was clearly different. Under low wall shear
      rate, aggregates were composed of bacterial cells able to "vibrate" independently
      on the surface, whereas, under a high wall shear rate, aggregates were more
      cohesive. Therefore, susceptibility to the hydraulic discontinuities occurring in
      drinking water system may not be similar. In all the flow chambers, significant
      decreases in bacterial biomass (up to 77%) were associated with the presence of
      amoebae. This grazing preferentially targeted small, isolated cells.

PMID- 17216656
TI  - Cell patterning using magnetite nanoparticles and magnetic force.
AB  - Technologies for fabricating functional tissue architectures by patterning cells
      precisely are highly desirable for tissue engineering. Although several cell
      patterning methods such as microcontact printing and lithography have been
      developed, these methods require specialized surfaces to be used as substrates,
      the fabrication of which is time consuming. In the present study, we demonstrated
      a simple and rapid cell patterning technique, using magnetite nanoparticles and
      magnetic force, which enables us to allocate cells on arbitrary surfaces.
      Magnetite cationic liposomes (MCLs) developed in our previous study were used to
      magnetically label the target cells. When steel plates placed on a magnet were
      positioned under a cell culture surface, the magnetically labeled cells lined on
      the surface where the steel plate was positioned. Patterned lines of single cells
      were achieved by adjusting the number of cells seeded, and complex cell patterns
      (curved, parallel, or crossing patterns) were successfully fabricated. Since cell
      patterning using magnetic force may not limit the property of culture surfaces,
      human umbilical vein endothelial cells (HUVECs) were patterned on Matrigel,
      thereby forming patterned capillaries. These results suggest that the novel cell
      patterning methodology, which uses MCLs, is a promising approach for tissue
      engineering and studying cell-cell interactions in vitro.

PMID- 17216657
TI  - Prediction of mass transfer coefficients in non-Newtonian fermentation media
      using first-principles methods.
AB  - Bubble flows in non-Newtonian fluids were analyzed using first-principles methods
      with the aim to compute and predict mass transfer coefficients in such
      fermentation media. The method we used is a Direct Numerical Simulation (DNS) of
      the reactive multiphase flow with deformable boundaries and interfaces. With this
      method, we are able for the first time to calculate mass transfer coefficients in
      non-Newtonian liquids of different rheologies without any experimental data. In
      the current article, shear-thinning fluids are considered. However, the results
      provide the basis for further investigations, such as the study of viscoelastic
      fluids.

PMID- 17216658
TI  - A multi-step kinetic model for substrate assimilation and bacterial growth:
      application to benzene biodegradation.
AB  - A multi-step kinetic model based on the concept of synthesizing unit (SU) was
      developed for describing benzene biodegradation in Pseudomonas putida F1. The
      model herein presented considered substrate arrival rates to the SU rather than
      concentrations, and provided a reasonable good fit of the dynamics of both
      catechol and biomass concentrations experimentally determined. It was based on
      very general assumptions and could be applied to any process accumulating
      metabolic intermediates. Conventional growth models considering a single step can
      be regarded as a particular case of this multi-step model. Despite the merits of
      this model, its applicability strongly depends on the knowledge of the complex
      induction-repression and inhibition mechanisms governing the different catabolic
      steps of the degradation pathway, which in most cases are difficult to elucidate
      experimentally and/or to model mathematically. In this particular case repression
      of benzene oxidation by catechol and self-inhibition of catechol transformation
      were experimentally confirmed and considered in the simulation, resulting in a
      good fit (relative average error of 6%) of the experimental data.

PMID- 17216659
TI  - Optimization of a jet-propelled particle injection system for the uniform
      transdermal delivery of drug/vaccine.
AB  - A jet-propelled particle injection system, the biolistics, has been developed and
      employed to accelerate micro-particles for transdermal drug delivery. We have
      examined a prototype biolistic device employing a converging-diverging supersonic
      nozzle (CDSN), and found that the micro-particles were delivered with a wide
      velocity range (200-800 m/s) and spatial distribution. To provide a controllable
      system for transdermal drug delivery, we present a contoured shock-tube (CST)
      concept and its embodiment device. The CST configuration utilizes a quasi-steady,
      quasi-one dimensional and shock-free supersonic flow to deliver the micro
      particles with an almost uniform velocity (the mean velocity and the standard
      deviation, 699 +/- 4.7 m/s) and spatial distribution. The transient gas and
      particle dynamics in both prototype devices are interrogated with the validated
      computational fluid dynamics (CFD) approach. The predicted results for static
      pressure and Mach number histories, gas flow structures, particle velocity
      distributions and gas-particle interactions are presented and interpreted. The
      implications for clinical uses are discussed.

PMID- 17216660
TI  - Sulfide oxidation at halo-alkaline conditions in a fed-batch bioreactor.
AB  - A biotechnological process is described to remove hydrogen sulfide (H(2)S) from
      high-pressure natural gas and sour gases produced in the petrochemical industry.
      The process operates at halo-alkaline conditions and combines an aerobic sulfide
      oxidizing reactor with an anaerobic sulfate (SO(4) (2-)) and thiosulfate
      (S(2)O(3) (2-)) reducing reactor. The feasibility of biological H(2)S oxidation
      at pH around 10 and total sodium concentration of 2 mol L(-1) was studied in gas
      lift bioreactors, using halo-alkaliphilic sulfur-oxidizing bacteria (HA-SOB).
      Reactor operation at different oxygen to sulfide (O(2):H(2)S) supply ratios
      resulted in a stable low redox potential that was directly related with the
      polysulfide (S(x) (2-)) and total sulfide concentration in the bioreactor.
      Selectivity for SO(4) (2-) formation decreased with increasing S(x) (2-) and
      total sulfide concentrations. At total sulfide concentrations above 0.25 mmol L(
      1), selectivity for SO(4) (2-) formation approached zero and the end products of
      H(2)S oxidation were elemental sulfur (S(0)) and S(2)O(3) (2-). Maximum
      selectivity for S(0) formation (83.3+/-0.7%) during stable reactor operation was
      obtained at a molar O(2):H(2)S supply ratio of 0.65. Under these conditions,
      intermediary S(x) (2-) plays a major role in the process. Instead of dissolved
      sulfide (HS(-)), S(x) (2-) seemed to be the most important electron donor for HA
      SOB under S(0) producing conditions. In addition, abiotic oxidation of S(x) (2-)
      was the main cause of undesirable formation of S(2)O(3) (2-). The observed
      biomass growth yield under SO(4) (2-) producing conditions was 0.86 g N mol(-1)
      H(2)S. When selectivity for SO(4) (2-) formation was below 5%, almost no biomass
      growth was observed.

PMID- 17216661
TI  - Flow modeling in a novel non-perfusion conical bioreactor.
AB  - We have developed a bioreactor vessel design which has the advantages of
      simplicity and ease of assembly and disassembly, and with the appropriately
      determined flow rate, even allows for a scaffold to be suspended freely
      regardless of its weight. This article reports our experimental and numerical
      investigations to evaluate the performance of a newly developed non-perfusion
      conical bioreactor by visualizing the flow through scaffolds with 45 degrees and
      90 degrees fiber lay down patterns. The experiments were conducted at the
      Reynolds numbers (Re) 121, 170, and 218 based on the local velocity and width of
      scaffolds. The flow fields were captured using short-time exposures of 60 microm
      particles suspended in the bioreactor and illuminated using a thin laser sheet.
      The effects of scaffold fiber lay down pattern and Reynolds number were obtained
      and correspondingly compared to results obtained from a computational fluid
      dynamics (CFD) software package. The objectives of this article are twofold: to
      investigate the hypothesis that there may be an insufficient exchange of medium
      within the interior of the scaffold when using our non-perfusion bioreactor, and
      second, to compare the flows within and around scaffolds of 45 degrees and 90
      degrees fiber lay down patterns. Scaffold porosity was also found to influence
      flow patterns. It was therefore shown that fluidic transport could be achieved
      within scaffolds with our bioreactor design, being a non-perfusion vessel. Fluid
      velocities were generally same of the same or one order lower in magnitude as
      compared to the inlet flow velocity. Additionally, the 90 degrees fiber lay down
      pattern scaffold was found to allow for slightly higher fluid velocities within,
      as compared to the 45 degrees fiber lay down pattern scaffold. This was due to
      the architecture and pore arrangement of the 90 degrees fiber lay down pattern
      scaffold, which allows for fluid to flow directly through (channel-like flow).

PMID- 17216662
TI  - Encapsulation of proteins in biodegradable polymeric microparticles using
      electrospray in the Taylor cone-jet mode.
AB  - Solvent extraction (or evaporation from a W(1)/O/W(2)-dispersion), coacervation,
      and spray drying methods are commonly employed to encapsulate protein drugs in
      polymeric microparticles for sustained delivery applications. To overcome the
      limitations of these methods, a novel electrospray method was developed to
      encapsulate a model protein drug-bovine serum albumin (BSA) in biodegradable
      polymeric microparticles and examine the feasibility of the process in not
      denaturing the protein. Microparticles of approximately 20 microm diameter with
      corrugated surfaces and smooth surfaces were observed by scanning electron
      microscope. Confocal laser scanning microscope images showed that BSA was
      distributed evenly in microparticles. Sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) was employed to investigate the protein integrity of
      BSA released from the polymer matrix after 38 days. No protein degradation was
      observed during the 38 days release. The secondary structure of released BSA was
      characterized by Fourier transform infrared (FTIR) and circular dichroism (CD),
      which suggested that the released BSA was almost identical to native BSA. The
      encapsulation efficiency could reach 76% by adjusting the amount of the additive
      Pluronic F127 and processing parameters. The release profile could be tailored by
      the fabrication process and the sustained release of BSA could endure for more
      than 1 month. More than 80% of the bioactivity of BSA (evaluated by BSA ELISA
      kit) could be maintained after releasing from polymer matrix. Findings of the
      present study demonstrate that this novel electrospray method is a promising
      approach to encapsulate bioactive materials such as proteins, enzymes,
      antibiotics, and DNA fragments in biodegradable polymeric particles.

PMID- 17216663
TI  - Distributed state simulation of endogenous processes in biological wastewater
      treatment.
AB  - Distributed state-type simulations (based on modeling of individual bacteria as
      they move through a reactor system) predicted a greater sensitivity of enhanced
      biological phosphorus removal (EBPR) performance to endogenous degradation than
      did conventional, "lumped"-type simulations (based on average biomass
      compositions). Recent research has indicated that the variable hydraulic
      residence times experienced by individual microbial storage product accumulating
      bacteria in systems with completely mixed reactors tend to produce populations
      with diverse microbial storage product contents (distributed states). Endogenous
      degradation in EBPR systems is of particular interest because the polyphosphate
      accumulating organisms (PAOs) responsible for EBPR rely on the accumulation of
      three different storage products that may be endogenously degraded. Simulations
      indicated that as endogenous degradation rates of microbial storage products were
      increased, EBPR performance decreased more rapidly according to the distributed
      approach than according to the lumped approach. State profile analysis
      demonstrated that as these rates increased, the population fraction with depleted
      storage products also increased, and this tended to increase the error in
      calculated biokinetic rates by the lumped approach. Simulations based on recently
      reported endogenous rate coefficients also suggested large differences between
      distributed and lumped predictions of EBPR performance. These results
      demonstrated that endogenous decay processes may play a more important role in
      EBPR than predicted by the lumped approach. This suggests a need for further
      research to determine endogenous process rates, and for incorporation of this
      information to distributed-type simulators, as this should lead to improved
      accuracy of EBPR simulations.

PMID- 17216664
TI  - Biosynthesis of the 2-pyridone tenellin in the insect pathogenic fungus Beauveria
      bassiana.
AB  - Genomic DNA from the insect pathogenic fungus Beauveria bassiana was used as a
      template in a PCR with degenerate primers designed to amplify a fragment of a C
      methyl transferase (CMeT) domain from a highly reduced fungal polyketide synthase
      (PKS). The resulting 270-bp PCR product was homologous to other fungal PKS CMeT
      domains and was used as a probe to isolate a 7.3-kb fragment of genomic DNA from
      a BamH1 library. Further library probing and TAIL-PCR then gave a 21.9-kb contig
      that encoded a 12.9-kb fused type I PKS-NRPS ORF together with ORFs encoding
      other oxidative and reductive enzymes. A directed knockout experiment with a BaR
      cassette, reported for the first time in B. bassiana, identified the PKS-NRPS as
      being involved in the biosynthesis of the 2-pyridone tenellin. Other fungal PKS
      NRPS genes are known to be involved in the formation of tetramic acids in fungi,
      and it thus appears likely that related compounds are precursors of 2-pyridones
      in fungi. B. bassiana tenellin KO and WT strains proved to be equally pathogenic
      towards insect larvae; this indicated that tenellin is not involved in insect
      pathogenesis.

PMID- 17216665
TI  - Complexation of fatty acids and fatty acid-CoAs with synthetic O-methylated
      polysaccharides.
AB  - An experimentally simple, but highly reproducible and reliable method has been
      developed to follow the complexation event of fatty acid (FA) and FA-CoA with
      polysaccharides. This method was based on the recent discovery of the unique blue
      shifted UV absorption associated with the aggregation of tetraenoic fatty acids
      (TE-FAs) in aqueous solution. Complexation was monitored by recording the
      intensity of UV absorption at 250 nm ([free TE-FA]) and 303 nm ([complexed TE
      FA]), and the K aggregate of C(20) t,t,t,t-TE-FA exhibited the ideal property for
      this purpose. Synthetic 3-O-methyl-D-mannose- and 6-O-methyl-D-glucose-containing
      lipopolysaccharides were found to exhibit a broad range of the binding affinities
      with C(20) t,t,t,t-TE-FAs as well as saturated FAs/FA-CoAs.

PMID- 17216666
TI  - Direct identification of proteins from T47D cells and murine brain tissue by
      matrix-assisted laser desorption/ionization post-source decay/collision-induced
      dissociation.
AB  - The purpose of this study is to determine the feasibility of the direct matrix
      assisted laser desorption/ionization (MALDI) identification of proteins in fixed
      T47D breast cancer cells and murine brain tissues. The ability to identify
      proteins from cells and tissue may lead to biomarkers that effectively predict
      the onset of defined disease states, and their dynamic behavior could be an
      important hint for drug target discoveries. Direct tissue application of trypsin
      allows protein identification in cells and tissues, while maintaining spatial
      integrity and intracellular organization. Using a chemical printer, matrix was co
      registered on trypsinized human T47D breast cancer cells and cryo-preserved
      sections of murine brain tissue, followed by MALDI post-source decay (PSD) or
      MALDI collision-induced dissociation (CID), respectively. Mass-to-charge (m/z)
      data from the cells and brain tissues were processed using Mascot software
      interrogation of the National Center for Biotechnology Information (NCBI)
      database. Histone H2B was identified from cultured T47D human breast cancer
      cells. Tubulin beta2 was identified from mouse brain cortex following an induced
      stroke. These results suggest that MALDI PSD/CID, combined with bioinformatics,
      can be used for the direct identification of proteins from cells and tissues.
      Refinements in preparation techniques may improve this approach to provide a tool
      for quantitative proteomics and clinical analysis.

PMID- 17216667
TI  - Prior data for non-normal priors.
AB  - Data augmentation priors facilitate contextual evaluation of prior distributions
      and the generation of Bayesian outputs from frequentist software. Previous papers
      have presented approximate Bayesian methods using 2x2 tables of 'prior data' to
      represent lognormal relative-risk priors in stratified and regression analyses.
      The present paper describes extensions that use the tables to represent
      generalized-F prior distributions for relative risks, which subsume lognormal
      priors as a limiting case. The method provides a means to increase tail-weight or
      skew the prior distribution for the log relative risk away from normality, while
      retaining the simple 2x2 table form of the prior data. When prior normality is
      preferred, it also provides a more accurate lognormal relative-risk prior in for
      the 2x2 table format. For more compact representation in regression analyses, the
      prior data can be compressed into a single data record. The method is illustrated
      with historical data from a study of electronic foetal monitoring and neonatal
      death.

PMID- 17216668
TI  - Data exploration in meta-analysis with smooth latent distributions.
AB  - Meta-analysis with discrete outcomes is interpreted as the estimation (in one or
      two dimensions) of a non-parametric smooth latent distribution of event
      probabilities (or rates). A simple but efficient EM algorithm is presented. A
      fine grid is used and fast smoothing is done by penalized least squares. Data
      exploration is the primary goal, but the estimated distribution can also be used
      to compute useful statistics of treatment effects.

PMID- 17216670
TI  - Shouldn't standard rheumatology clinical care be evidence-based rather than
      eminence-based, eloquence-based, or elegance-based?

PMID- 17216671
TI  - The challenge of early diagnosis in ankylosing spondylitis.

PMID- 17216672
TI  - Cartilage is held together by elastic carbohydrate strings. Implications in
      osteoarthrosis.

PMID- 17216673
TI  - Predicting physical activity and general health perception among patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To describe changes over one year in physical activity, body
      functions, and disease activity in patients with rheumatoid arthritis (RA) and to
      identify predictors for physical activity and general health perception. METHODS:
      One hundred two patients with RA were recruited for the study (median age 57 yrs,
      range 19-84; median disease duration 15 mo, range 4-78; 76% women). Self-reported
      data on physical activity and health locus of control, tests of lower extremity
      function, grip force, joint range of motion, balance, and measures of disease
      activity, including pain, general health perception, Health Assessment
      Questionnaire (HAQ), and Disease Activity Score (DAS28), were collected on 2
      occasions, one year apart. Each variable was dichotomized to fit logistic
      regression models, performed to identify which variables predicted physical
      activity and general health perception over one year. RESULTS: Physical activity
      was stable, while lower extremity function, grip force, and range of motion
      improved and DAS28 decreased significantly over one year. A high physical
      activity level at baseline was the only predictor of high physical activity (odds
      ratio 3.85, 95% confidence interval 1.67-9.09) one year later. Low pain (OR 8.47,
      95% CI 2.97-24.39), high physical activity (OR 3.72, 95% CI 1.39-10.10), and good
      lower extremity function (OR 2.94, 95% CI 1.04-8.33) were identified as
      predictors of good general health perception. CONCLUSION: While pain is a well
      known predictor of general health perception, to our knowledge, this is the first
      study to identify predictive factors related to physical activity and lower
      extremity function as important for perceived health among patients with RA.

PMID- 17216674
TI  - Tumor necrosis factor-alpha induces vascular endothelial growth factor-C
      expression in rheumatoid synoviocytes.
AB  - OBJECTIVE: To determine the expression of vascular endothelial growth factor-C
      (VEGF-C) in the synovial fluid of patients with rheumatoid arthritis (RA) and to
      investigate the regulation of VEGF-C production by major proinflammatory
      cytokines in fibroblast-like synoviocytes (FLS). METHODS: The concentrations of
      VEGF-C, tumor necrosis factor-alpha (TNF-alpha), and interleukin 1beta (IL-1beta)
      were measured using an ELISA method in synovial fluids obtained from 20 patients
      with RA and 20 with osteoarthritis (OA). Primary cultured RA FLS were stimulated
      with TNF-alpha or IL-1beta, and the expression levels of VEGF-C mRNA and protein
      were assessed by quantitative real-time polymerase chain reaction and ELISA.
      RESULTS: Significantly higher levels of VEGF-C were found in RA synovial fluids
      compared to OA synovial fluids. VEGF-C levels showed a highly significant
      correlation with the levels of both TNF-alpha and IL-1beta in the synovial fluid
      of patients with RA. TNF-alpha stimulation significantly increased VEGF-C mRNA
      and protein expression in RA FLS in a dose-dependent manner. A tendency to
      increased expression of VEGF-C was also observed after IL-1beta stimulation in
      FLS. CONCLUSION: Overexpression of VEGF-C in FLS by stimulation with TNF-alpha
      may play an important role in the progression of synovial inflammation and
      hyperplasia in RA by contributing to local lymphangiogenesis and angiogenesis.

PMID- 17216675
TI  - Overexpression of A3 adenosine receptor in peripheral blood mononuclear cells in
      rheumatoid arthritis: involvement of nuclear factor-kappaB in mediating receptor
      level.
AB  - OBJECTIVE: A3 adenosine receptor (A3AR) upregulation has been found in cells of
      synovial tissue and in peripheral blood mononuclear cells (PBMC) of rats with
      adjuvant-induced arthritis. We investigated A3AR levels in PBMC of patients with
      rheumatoid arthritis (RA) and in mitogen-activated PBMC from healthy subjects. We
      examined the role of nuclear factor-kappaB (NF-kappaB), a transcription factor
      present in the A3AR promoter, in mediating receptor upregulation. METHODS: A3AR
      and NF-kappaB protein levels were evaluated in PBMC of RA patients (n = 23) and
      healthy subjects by Western blot. A3AR and NF-kappaB levels were also analyzed in
      phytohemagglutinin (PHA) and lipopolysaccharide (LPS)-stimulated PBMC in the
      presence and absence of antibodies against interleukin 2 (IL-2) and tumor
      necrosis factor-alpha (TNF-alpha). Reverse transcription-polymerase chain
      reaction was performed in PHA-stimulated PBMC of healthy subjects to determine
      A3AR expression. RESULTS: A3AR was overexpressed in PBMC of RA patients compared
      to healthy subjects and was directly correlated to an increase in NF-kappaB.
      Similar findings were observed in PHA and LPS-stimulated PBMC from healthy
      subjects. Antibodies against IL-2 or TNF-alpha prevented the increase in A3AR and
      NF-kappaB expression. CONCLUSION: Overexpression of A3AR was found in PBMC of RA
      patients. Receptor upregulation was induced by inflammatory cytokines controlling
      the expression of the A3AR transcription factor NF-kappaB.

PMID- 17216676
TI  - Blockade of vascular endothelial growth factor activity suppresses wear debris
      induced inflammatory osteolysis.
AB  - OBJECTIVE: Aseptic loosening is a common complication of total joint replacement
      in humans. Our study examined the hypothesis that wear debris may influence
      vascular endothelial grow factor (VEGF) expression, and that blocking VEGF
      bioactivity might improve wear debris-induced inflammatory osteolysis in a mouse
      model. METHODS: Ultra high molecular weight polyethylene (UHMWPE) particles were
      introduced into established air pouches on BALB/c mice, followed by implantation
      of calvaria bone from syngeneic littermates. Mice were treated with recombinant
      VEGF, or VEGF inhibitor (VEGF R2/Fc chimera) or vehicle control, and mice without
      UHMWPE stimulation were also included. Pouch tissues were harvested 2 weeks after
      bone implantation for molecular and histological analyses. RESULTS: Exposure of
      UHMWPE particles increased VEGF expression at both mRNA and protein levels in
      pouch tissues. Immunostaining revealed intense VEGF staining predominantly in
      UHMWPE deposit foci surrounded by inflammatory cells. VEGF inhibitor treatment
      strongly attenuated tissue inflammation (cellular infiltration, membrane
      proliferation, and expression of interleukin 1beta and tumor necrosis factor
      alpha in UHMWPE-stimulated pouch tissues). Further, VEGF inhibitor treatment
      caused a significant reduction in the number of TRAP+ cells, and effectively
      prevented UHMWPE particle-induced bone resorption of implanted calvaria (assessed
      by extent of collagen depletion and frequency of bone erosions). CONCLUSION: The
      observation that VEGF inhibitor treatment prevented UHMWPE particle-induced
      inflammatory osteolysis opens new possibilities for treatment of aseptic
      loosening, especially at an early stage.

PMID- 17216677
TI  - Prognosis of 5-year radiographic erosions of the wrist according to early, late,
      and persistent wrist swelling or tenderness in patients with early rheumatoid
      arthritis.
AB  - OBJECTIVE: To determine whether early inflammatory activity in the first year of
      disease compared to persistent or later occurrence of swelling or tenderness in
      the wrist joints is associated with 5-year erosions in the same joint in patients
      with early rheumatoid arthritis (RA). METHODS: A cohort of 195 patients with
      early active RA was enrolled in the Finnish RA Combination Trial. Swelling and
      tenderness of wrists were assessed at baseline and at 3, 6, 12, 24, 36, and 48
      months. Radiographs of the wrists were taken at the baseline and at 5 years. The
      237 wrist joints of 125 patients without erosions at baseline were classified
      according to wrist swelling, i.e., I: never swollen; II: swollen during first
      year only; III: swollen during the second to fourth year only; and IV: swollen
      during the first year and followup, and similarly according to tenderness.
      RESULTS: Thirty percent of the wrists were never swollen in all clinical
      examinations; 43% were swollen only during the first year; 11% were not swollen
      in the first year, but were swollen at some time during 24-48 months; and 16% of
      wrists were swollen during the first year and at some time during 24-48 months.
      At 5 years, 64% of 237 wrists remained free of erosions. Erosions developed in
      82% of wrists that were swollen during both the first year and 24-48 months,
      versus 56% of wrists that were not swollen at first year but were swollen during
      24-48 months, 31% of wrists that were swollen during the first year only, and 11%
      of wrists that were never swollen. Similar results were seen for joint
      tenderness. CONCLUSION: Wrist swelling during the first year only is associated
      with less future wrist radiographic damage than persistent swelling or swelling
      only during the followup. Our results emphasize the value of early and continuous
      suppression of inflammatory activity in early RA.

PMID- 17216678
TI  - Patient self-administered joint tenderness counts in rheumatoid arthritis are
      reliable and responsive to changes in disease activity.
AB  - OBJECTIVE: To examine whether self-assessment of tender and swollen joints by
      patients with rheumatoid arthritis (RA) can be used to evaluate changes in
      disease activity instead of joint counts by physicians. METHODS: Eighty-two
      patients with RA taking part in controlled studies were recruited for
      investigation. The patient's self-assessment of joint tenderness and swelling was
      completed both before and 30 minutes after examination by a physician.
      Examinations of tender and swollen joints by a rheumatologist were performed at
      baseline and 3 months later. The correlations and verification of agreement of
      these clinical assessments were analyzed. RESULTS: Within-patient and patient
      physician correlations for joint tenderness counts were high (r = 0.96 and 0.78,
      respectively). Patient-physician correlation for joint swelling counts was still
      significant, although much lower (r = 0.34). Patients' and physicians'
      estimations of the change in disease activity over 3 months did not differ (p >
      0.76 for all comparisons). CONCLUSION: Joint tenderness counts were consistent
      when comparing intra-patient and patient-physician assessments, while joint
      swelling counts were poorly correlated. Patient and physician assessments of
      change over 3 months were parallel and similar for joint tenderness count. Self
      administered tender joint counts might be a useful tool to evaluate the response
      to therapy in RA.

PMID- 17216679
TI  - Color and duplex Doppler sonography to detect sacroiliitis and spinal
      inflammation in ankylosing spondylitis. Can this method reveal response to anti
      tumor necrosis factor therapy?
AB  - OBJECTIVE: To investigate the role of color and duplex Doppler ultrasound (CDDUS)
      in the detection of sacroiliac (SI) and spinal inflammation, as well as response
      to anti-tumor necrosis factor (TNF) therapy in patients with ankylosing
      spondylitis (AS). METHODS: We included 39 consecutive patients with AS followed
      at our center and 14 healthy controls. In the AS and control groups, blood
      vessels in SI joints and lumbar vertebral (LV) and thoracal vertebral (TV)
      paraspinal areas were investigated by CDDUS. When the artery was found, the
      resistive index (RI) was measured by CDDUS. Disease activity characteristics
      (ESR, CRP, BASDAI, and BASMI) were evaluated in patients with AS. In 11 patients
      for whom anti-TNF therapy was indicated, CDDUS measurements were performed before
      and on Week 12 of therapy. RESULTS: In patients with AS, RI values of SI joints
      and of LV and TV areas were lower than in controls (all p < or = 0.01). In AS
      patients with active disease according to BASDAI, RI values of TV (p = 0.0013)
      and LV (p = 0.027) were significantly lower than in the inactive group. In the
      group with active AS, SI RI was nonsignificantly lower (p = 0.16). After anti-TNF
      therapy, there were significant increases in mean SI RI (p = 0.028) and LV RI (p
      = 0.039), and a nonsignificant increase in TV RI (p > 0.05). CONCLUSION: CDDUS
      may be an alternative, less expensive, and easier method for detecting
      inflammation secondary to increased SI and spinal vascularization and in
      evaluating response to anti-TNF therapy in AS.

PMID- 17216680
TI  - The modified Nail Psoriasis Severity Index: validation of an instrument to assess
      psoriatic nail involvement in patients with psoriatic arthritis.
AB  - OBJECTIVE: Patients with psoriasis and psoriatic arthritis (PsA) commonly have
      nail involvement. There is no validated psoriatic nail assessment tool. Recently,
      investigators developed the Nail Psoriasis Severity Index (NAPSI). Beginning with
      NAPSI, our goal was to validate a psoriatic nail assessment tool for use in
      clinical trials, and investigate correlations between nail and other PsA
      features. METHODS: Fingernails of 29 patients with PsA were photographed and
      scored. Clinical data were collected. Using the original NAPSI, analysis revealed
      high interrater variability of nail scores. Twenty patients' photographs were
      regraded using the modified NAPSI (mNAPSI). RESULTS: The mNAPSI scores had
      excellent interrater reliability (Cronbach's alpha 0.98). Nail scores and
      physicians' global nail severity visual analog scores showed good inter- and
      intrarater correlations (Spearman's rho 0.85 and 0.90-0.99, respectively; p <
      0.01). Several clinical measures correlated with nail scores. CONCLUSION: The
      mNAPSI demonstrated excellent interrater reliability and construct validity, and
      may be a valuable tool.

PMID- 17216681
TI  - Prevalence of depressive symptoms in postmenopausal women with low bone mineral
      density and/or prevalent vertebral fracture: results from the Multiple Outcomes
      of Raloxifene Evaluation (MORE) study.
AB  - OBJECTIVE: To examine the prevalence of depressive symptoms in a cross-sectional
      study of postmenopausal women with osteoporosis with and without prevalent
      vertebral fracture. METHODS: Participants were a subset of English-speaking women
      (n = 3798, mean age 66.7 yrs) from the Multiple Outcomes of Raloxifene Evaluation
      trial, who had low bone mineral density (BMD) and/or prevalent vertebral
      fractures. Vertebral fractures were measured at baseline by radiography using a
      semiquantitative technique. Depressive symptoms were assessed at baseline using
      the Geriatric Depression Scale (GDS), a valid and reliable scale for depression
      screening in elderly patients. Women were considered as probably depressed if >
      or = 6 symptoms of depression were reported. RESULTS: Postmenopausal women with
      prevalent vertebral fracture reported more depressive symptoms as assessed by the
      GDS than women without prevalent vertebral fracture (1.54 vs 1.26; p = 0.001).
      There was an absolute increase of 2.5% (p = 0.008) in the prevalence of probable
      depression (GDS score > or = 6) in women with prevalent fracture compared to
      those without prevalent fracture. The prevalence of probable depression was 4.1%
      among women without prevalent vertebral fracture and 6.6% in women with a
      prevalent vertebral fracture. The prevalence of probable depression was 3-fold
      higher in women with at least 3 prevalent vertebral fractures compared to women
      without prevalent fracture (12.8% vs 4.1%; p < 0.001). CONCLUSION: Postmenopausal
      women with prevalent vertebral fractures had greater prevalence of depressive
      symptoms and probable depression as assessed by the GDS than women without
      vertebral fracture with low BMD. The dual diagnosis of depression and
      osteoporosis may mean worse health outcomes. Patients with prevalent vertebral
      fractures may be considered not only for interventions that address fracture risk
      reduction, but also for psychosocial interventions that address depressive
      symptoms.

PMID- 17216682
TI  - Variations in torsion of the lower limb in Japanese and Caucasians with and
      without knee osteoarthritis.
AB  - OBJECTIVE: Associations between torsion of the lower limb and knee osteoarthritis
      (OA) appear to be inconsistent across populations. We examined whether femoral
      and tibiofibular torsion differed between people with and without knee OA (main
      effect), and whether the differences were consistent across Japanese and
      Australian Caucasian persons, and between women and men (interaction effect).
      METHODS: Data collection was conducted in Japan and Australia. Subjects with knee
      OA included 100 Japanese and 102 Australian Caucasians, and healthy subjects
      included 52 Japanese and 34 Australian Caucasians. Femoral and tibiofibular
      torsion were measured using reliable clinical techniques. Three-way analysis of
      variance was conducted to examine the main and interaction effects. RESULTS:
      While there were no significant differences in femoral and tibiofibular torsion
      between the subjects with and without knee OA as a whole (main effect), there
      were significant interactions (p < 0.05). Femoral antetorsion was lower only in
      the female subjects with knee OA compared with their healthy counterparts (p <
      0.05). Tibiofibular torsion was lower only in the Japanese subjects with knee OA
      compared with their healthy counterparts (p < 0.01). CONCLUSION: There may be
      ethnic and sex variations in the relationship between torsion of the lower limb
      and knee OA; and lower tibiofibular torsion can be a characteristic in a Japanese
      population with the disease. Longitudinal study is warranted to examine
      relationships between these variables and knee OA in a population-specific manner
      to determine whether the observed relationships express cause or effect.

PMID- 17216683
TI  - Effect of therapeutic exercise and sleeping neck support on patients with chronic
      neck pain: a randomized clinical trial.
AB  - OBJECTIVE: To investigate the effects of therapeutic exercises and sleeping neck
      support contoured pillows on patients with chronic neck pain. METHODS: Using a
      factorial design in a prospective clinical trial, participants were equally
      allocated at random to 4 treatment groups in the study: (1) placebo control, of
      hot or cold packs and massage; (2) sleeping neck support pillow and placebo; (3)
      active neck exercises and placebo; and (4) combined exercise and sleeping neck
      support pillow and placebo. Participants were treated by physical therapists over
      a 6 week period and assessed by masked independent assessors at 0, 3, 6, 12, 24
      weeks, and 12 months, with the 12 week assessment being the primary decision
      time. The primary outcome measure was the Northwick Park Neck Pain Questionnaire
      (NPQ). RESULTS: For the 128/151 (85%) participants tested at 12 weeks, the NPQ
      descriptive statistics of count, mean (standard deviation) were: Initial: 128,
      31.0 (11.3) at Week 12; All: 128, 18.5 (11.6); CONTROL: 34, 18.6 (10.0); Pillow:
      32, 21.5 (13.1); Active neck exercises: 29, 20.1 (11.6); and Combined: 33, 14.1
      (10.6). Factorial analysis of variance showed that the main effects of Exercise
      (p = 0.146) and Pillow (p = 0.443) were not statistically significant; but the
      interaction of Exercise plus Pillow (p = 0.029) was statistically significant and
      clinically meaningful. CONCLUSION: Treatment by physiotherapists trained to teach
      both exercises and the use of a neck support pillow achieved the most favorable
      benefit for participants with chronic neck pain; either strategy alone was not
      more effective than a control regimen. Time was an important cofactor.

PMID- 17216684
TI  - Direct and indirect costs of osteoarthritis in Singapore: a comparative study
      among multiethnic Asian patients with osteoarthritis.
AB  - OBJECTIVE: To estimate and compare the direct and indirect costs of
      osteoarthritis (OA) in multiethnic Asian patients with OA in Singapore. METHODS:
      The study was a retrospective and cross-sectional design. Patients were
      stratified according to ethnicity and presence or absence of joint surgery.
      Direct costs were estimated from both a societal and a patient perspective using
      the Singapore General Hospital database; indirect costs were estimated using the
      human capital approach. All costs were expressed as mean costs per patient per
      annum in 2003 Singapore dollars. RESULTS: A total of 1179 patients (83.6%
      Chinese, 7.2% Malay, 3.5% Indian, 5.7% others) were included in estimating direct
      costs, of which 513 (43.5%) had total knee replacement (TKR) and 92 (7.8%) total
      hip replacement (THR), while 105 patients (71.4% Chinese, 14.3% Malay, 14.3%
      Indian) were included in estimating indirect costs. Direct costs to patients
      ranged from 1460 dollars to 7477 dollars for Chinese, 1362 dollars-7211 dollars
      for Malays, 1688 dollars-6226 dollars for Indians, and 1437 dollars-12,140
      dollars for other ethnic patients; direct costs to society ranged from 3351
      dollars to 15,799 dollars for Chinese, 2939 dollars-15,436 dollars for Malays,
      3150 dollars-10,990 dollars for Indians, and 2597 dollars-17,879 dollars for
      other ethnic patients. In contrast, the indirect costs ranged from 1215 dollars
      to 3834 dollars for Chinese, 1138 dollars-6116 dollars for Malays, and 1371
      dollars-5292 dollars for Indians. However, most ethnic variations were not
      statistically significant. CONCLUSION: The economic burden of OA to society and
      patients increased by 3-fold or more in the patients with TKR/THR compared to
      those without. The ethnic differences in health resources consumed were more
      apparent when the disease progressed.

PMID- 17216685
TI  - Prevalence of knee symptoms and radiographic and symptomatic knee osteoarthritis
      in African Americans and Caucasians: the Johnston County Osteoarthritis Project.
AB  - OBJECTIVE: To report contemporary estimates of the prevalence of knee-related
      osteoarthritis (OA) outcomes in African Americans and Caucasians aged > or = 45
      years. METHODS: Weighted prevalence estimates for knee symptoms, radiographic
      knee OA, symptomatic knee OA, and severe radiographic knee OA were calculated for
      age, ethnic, and sex subgroups, in 3018 participants (33% African Americans, 38%
      men) in the baseline examination (1991-97) of The Johnston County Osteoarthritis
      Project, a population-based study of OA in North Carolina. Radiographic knee OA
      was defined as Kellgren-Lawrence radiographic grade > or = 2, severe radiographic
      knee OA as grades 3 and 4, and symptomatic knee OA as knee symptoms in a knee
      with radiographic OA. RESULTS: Knee symptoms were present in 43%, 28% had
      radiographic knee OA, 16% had symptomatic knee OA, and 8% had severe radiographic
      knee OA. Prevalence was higher in older individuals and women. African Americans
      had slightly higher prevalence of knee symptoms, radiographic knee OA, and
      symptomatic knee OA, but significantly higher prevalence of severe radiographic
      knee OA compared to Caucasians. CONCLUSION: Policy should be directed to
      increasing education of the public and the medical community about the high
      prevalence of these conditions, especially in these subgroups, to decrease their
      impact and ultimately prevent them.

PMID- 17216686
TI  - A longitudinal study of the association between knee alignment and change in
      cartilage volume and chondral defects in a largely non-osteoarthritic population.
AB  - OBJECTIVE: It remains unclear whether malalignment of the knee is a cause of knee
      OA or a marker of disease progression. We investigated whether baseline
      malalignment of the knee predicts subsequent change in knee cartilage volume and
      chondral defects in subjects with and without radiographic knee osteoarthritis
      (OA). METHODS: A convenience sample of 315 male and female subjects (mean age 45
      yrs, range 26-61) was followed up for a mean period of 2.4 years. Anatomic knee
      alignment was assessed on a standing anterior-posterior semiflexed view of the
      right knee and defined as the angle subtended by a line drawn through the
      midshaft of the femur with respect to one drawn through the midshaft of the
      tibia. T1-weighted fat saturation magnetic resonance imaging scans were performed
      on the same knee at baseline and followup for cartilage volume and chondral
      defects. RESULTS: Knee alignment was normally distributed in this sample with a
      mean of 178.2 degrees (SD 1.9 degrees). Fifty-five percent of subjects were <
      178.5 degrees, while 14% were > 180 degrees. After adjustment for age, sex, body
      mass index, previous knee injury, and OA family history, neither category of
      alignment at baseline was associated with subsequent loss of lateral and medial
      tibial cartilage volume. Similarly, there was no association between malalignment
      and progression of chondral defects. The results remained the same when
      stratified by radiographic OA status. CONCLUSION: Our adequately powered study
      shows that baseline knee alignment is not associated with subsequent loss of
      cartilage volume or progression of chondral defects over 2 years. Further studies
      with a longterm followup are needed, but these results suggest malalignment is
      primarily a marker of disease progression.

PMID- 17216688
TI  - Musculoskeletal pain in Malaysia: a COPCORD survey.
AB  - OBJECTIVE: To assess the nature and extent of rheumatic complaints in a semirural
      area in a multiracial (Malay, Indian, Chinese) community in Malaysia using the
      Community Oriented Program for the Control of Rheumatic Diseases (COPCORD)
      protocol initiated by ILAR and the WHO. METHODS: All members of a community of
      2700 persons over the age of 15 years were offered a questionnaire based
      interview in Phase 1 of the study. Those with rheumatic complaints (pain in the
      last 1 week) were invited for a physical examination by a rheumatologist in Phase
      2. RESULTS: In total, 2594 (96%) persons agreed to a questionnaire based
      interview. Of those interviewed, 21.1% had a current rheumatic complaint. The
      pain rate was higher in women (23.8%) than in men (17.8%). Chinese men had the
      lowest age-standardized pain rate (9.9%), while Indian women had the highest rate
      (28.4%). In the study population, 14.4% complained of pain in the joints and/or
      musculoskeletal pain and 11.6% had low back pain. The knee was responsible for
      64.8% of all complaints pertaining to the joints, and more than half those
      examined with knee pain had clinical evidence of osteoarthritis (OA). The
      complaint rate increased with age, up to 53.4% in the group age > 65 years. The
      major disability encountered was the inability to squat (3.1%). Fibromyalgia,
      soft tissue lesions, and localized OA of the knees were the main clinical
      diagnoses. Inflammatory arthritis was uncommon. Both Western and traditional
      sources of healthcare were used, often together. Self-medication was common
      (58.8%). CONCLUSION: Knee and back pain are the main rheumatic complaints in
      Malaysia, with complaint rates differing according to race and gender.

PMID- 17216687
TI  - Increased cancer risk in patients referred to hospital with suspected
      fibromyalgia.
AB  - OBJECTIVE: To analyze whether fibromyalgia (FM) and FM-like symptoms are related
      to an increased incidence of cancer. METHODS: We identified 1361 patients
      referred on suspicion of FM in the period 1984-99 from hospital records.
      Following the American College of Rheumatology (ACR) criteria, patients were
      divided into subgroups with and without confirmed FM. The cohort was followed to
      the end of 1999 and linked to the files of the Danish Cancer Register. Site
      specific standardized incidence ratios (SIR) were calculated. RESULTS: We found
      no association between FM and cancer in 1132 female patients with confirmed FM at
      our institution (SIR 1.2, 95% CI 0.8-1.8). In 106 women referred for muscle pain
      and/or tenderness who did not meet the criteria for FM, an increased overall SIR
      was observed (SIR 2.5, 95% CI 1.2-4.6), with increased risk for breast cancer
      (SIR 4.8, 95% CI 1.6-11.3) and lymphatic and hematological cancers (SIR 10.6, 95%
      CI 1.2-38.2). There were 4 lung cancers in 84 men with confirmed FM (SIR 12.6,
      95% CI 3.4-32.4). CONCLUSION: Neither confirmed FM nor those without confirmed FM
      predicted cancer. An increased risk of breast cancer was found among those who
      did not meet the ACR criteria for FM. These patients should be investigated if
      they develop any new or warning symptoms of malignancy, and treating physicians
      should be vigilant with screening procedures such as mammography.

PMID- 17216689
TI  - GRAPPA--Group for Research and Assessment of Psoriasis and Psoriatic Arthritis,
      Stockholm, May/June 2006.

PMID- 17216690
TI  - Heart disease in rheumatoid arthritis: changing the paradigm of systemic
      inflammatory disorders.

PMID- 17216691
TI  - Rheumatoid nodule of the extensor tendons of the lower extremity.

PMID- 17216692
TI  - Carotidynia in Takayasu arteritis.

PMID- 17216694
TI  - Patient's ethnicity and use of therapies in rheumatoid arthritis.

PMID- 17216696
TI  - Juvenile idiopathic arthritis classification criteria: loopholes and diagnosis
      software.

PMID- 17216698
TI  - Carcinomas in patients with systemic lupus erythematosus.

PMID- 17216699
TI  - Neurological complications of infliximab.

PMID- 17216701
TI  - Neurological complications of infliximab.

PMID- 17216703
TI  - Interstitial pneumonitis and anti-tumor necrosis factor-alpha therapy.

PMID- 17216704
TI  - Adalimumab-associated multiple sclerosis.

PMID- 17216706
TI  - Macrophage activation syndrome after etanercept treatment.

PMID- 17216707
TI  - Quality disconnect. Tools not ready for pay-for-performance: study.

PMID- 17216708
TI  - MedPAC's regional approach. Industry executives see flaws in proposed formula.

PMID- 17216709
TI  - Inova ends liver transplants. Move comes as CMS scrutinizes programs nationally.

PMID- 17216710
TI  - Clinical challenges and images in GI. Image 1. Hepatic encephalopathy secondary
      to a spontaneous type 1 portosystemic shunt.

PMID- 17216711
TI  - An emerging consensus on grading recommendations?

PMID- 17216712
TI  - Erratum to "Diapause-associated metabolic traits reiterated in long-lived daf-2
      mutants in the nematode Caenorhabditis elegans" [Mech. Ageing Dev. 127 (5) (2006)
      458-472].
AB  - The longevity of the Caenorhabditis elegans diapausal dauer larva greatly exceeds
      that of the adult. Dauer formation and adult ageing are both regulated by
      insulin/IGF-1 signalling (IIS). Reduced IIS, e.g. by mutation of the daf-2
      insulin/IGF-1 receptor gene, increases adult lifespan. This may reflect mis
      expression in the adult of dauer longevity-assurance processes. Since IIS plays a
      central role in the regulation of metabolism, metabolic alterations shared by
      dauer larvae and daf-2 adults represent candidate mechanisms for lifespan
      determination. We have conducted a detailed comparison of transcript profile data
      from dauers and daf-2 mutant adults, focusing on expression of metabolic pathway
      genes. Our results imply up-regulation in both dauers and daf-2 mutant adults of
      gluconeogenesis, glyoxylate pathway activity, and trehalose biosynthesis. Down
      regulation of the citric acid cycle and mitochondrial respiratory chain occurs in
      dauers, but not daf-2 adults. However, the F1 ATPase inhibitor was up-regulated
      in both, implying enhanced homeostasis in conditions where mitochondria are
      stressed. Overall, the data implies increased conversion of fat to carbohydrate,
      and conservation of ATP stocks in daf-2 mutant adults, suggesting a state of
      increased energy availability. We postulate that this fuels increased somatic
      maintenance activity, as suggested by the disposable soma theory.

PMID- 17216713
TI  - [Changes in the rabbit brain cortex redox potential accompaning episodes of ECoG
      arousal during slow-wave sleep].
AB  - Local cortex E variations are well expressive indices of rate and peculiarities
      of energy metabolism. The brain E is determined by the ratio of processes
      occurring in two energy compartments in glycolysis, in whish glucose is split
      without oxygen utilization and in oxidative metabolism. In the present
      investigation, the brain cortex E changes were recorded with implanted platinum
      electrodes during slow wave sleep. Under such conditions, the E lowering detects
      acceleration in glycolytic compartment, whereas the E local rising shows
      acceleration in oxidative metabolism in the tissue surrounding the electrode.
      Earlier in rats, we have found that E significantly lowered in metabolic active
      cortical sites during episodes of SWS, and supposed that acceleration of
      glycolysis increased. Slow oscillations (a 20-40-sec prolongation of the
      amplitude up to several dozens millivolts) appeared at the same time. We
      considered these E slow oscillations to reflect changes in the rate in
      compartment of glycolysis. In this research, we have found the E slow
      oscillations to be created by regular episodes of ECoG-arousal which were
      accompanied by E decreases, i. e. by acceleration in glycolysis. We think the
      data presented show existence of functional system supporting a low level of
      arousal. As in any complex system with feed back connections, this system works
      in oscillatory regime.

PMID- 17216714
TI  - [Motor and cognitive functions of the neostriatum during bilateral blocking of
      its dopamine receptors].
AB  - In experiments on 60 Sprague-Dawley rats, effects of systemic and intrastriatal
      injections of se-lective blocker of D1 receptors SCH23390 on elaboration of
      discriminational conditioned reflex of active avoidance (CRAA) were studied in T
      maze and on behavior in test of the "open field". Systemic administration of this
      inhibitor at doses of 0.025 mg/kg produced a several fold decrease of percentage
      of correct realizations of the discriminational CRAA and of motor activity in the
      "open field" test. Bilateral microinjections of SCH23390 into the rat neostriatum
      at a dose of 0.004-1.0 mkg did not deteriorate learning of the discriminational
      CRAA as compared with intact control, although a marked inhibition of motor
      activity was observed in the open field, test. Analysis of the data has also
      shown a statistically significant decrease of percentage of errors in the
      starting maze compartment in experiments with intrastriatal injection of SCH23390
      to rats. At the same time, the intrastriatal injection to rats of raclopride, a
      blocker of D2 dopamine receptors, at a dose of 0.004 mkg produced a sharp and
      prolonged deterioration of learning of the discriminational CRAA. The data
      obtained have allowed the following conclusions to be made: 1. Difference of
      effects of the systemic and intrastriatal SCH23390 injections seems to be due to
      that the behavioral changes observed at the systemic administration can be
      provided predominanantly by structures differing from neostriatal D1 receptors;
      2. Effect of nigrostriatal dopaminergic system on the neostriatum through D1
      receptors is complex: activation of motor activity (efferent spine cells of the
      direct pathway) and a poor modulation of the learning process (large aspine
      cholinergic interneurons); 3. The modulation of the learning process seems to
      occur through neostriatal D2 receptors (large aspine cholinergic interneurons).

PMID- 17216715
TI  - [The dynamics of neuron activity level in the striatum of the monkey brain in
      relation to the realization of multistage behavior].
AB  - Level of the unit activity was studied in the monkey putamen during multistage
      behavior. Two groups of neuron activity patterns were distinguished. The first
      one involved patterns of low level neuron activity less exceeding the background
      level than the second one; the other group involved patterns of high level neuron
      activity exceeding the background level in the second time. These kinds of
      patterns were behavior-related. Patterns with low level neuron activity were
      recorded preferentially in relation to the trigger stimuli and reward. Patterns
      of high level neuron activity were recorded in relation to the decision-making,
      movements of arms in the left and right directions. Besides, their number rose in
      relation to the auditory cue reported to right realization of the task. It was
      established that the number of patterns of high level neuron activity rose in key
      moments of behavior, while the number of the patterns of low level neuron
      activity decreased.

PMID- 17216716
TI  - [c-FOS protein expression in cells of the variuos hypothalamic structures after
      electric pain stimulation and injections of antigens].
AB  - Hypothalamic structures become activated after stimul. Alteration of c-Fos
      positive cells quantity in different hypothalamic structures after electric pain
      stimulation (EPS), intravenous (iv) injection of antigens (lioppolysaccharide
      (LPS) and bovine serum albumir (BSA)) was detected with immunohistochemical
      method. EPS and iv injection of antigens (LPS and BSA) result in c-Fos-positive
      cells quantity increase in all observed hypothalamic structures. The highest
      activation level was in AHN and PH after EPS and in AHN, PVH, LHA-28, and PH
      after iv LPS injection. Comparative analysis of results showed, that c-Fos
      positive cells quantity increase after EPS in AHN, PVH, LHA and PH was more
      significant than after iv injection of antigens (LPS and BSA). LPS injection
      results in more pronounced cell activation in AHN, PVH, LHA-28 and DMH (according
      to quantity of c-Fos-positive cells), than BSA injection.

PMID- 17216717
TI  - [Role of neuropeptide galanin in formation of the typical behavioural
      characteristics].
AB  - Blockade of central galanin receptors through intranasal treatment with specific
      antagonis M-35 changes the behavioral reactions to novel conditions: the animals
      treated with M-35 show decreased exploratory activity and increased anxiety level
      in open field test. The level of pre-progalanin mRNA expression in brain
      structures was investigated in Wistar rats with opposite strategies of behaviors
      in open field test. A higher level of pre-progalanin mRNA in anterior
      hypothalamus of "active" rats was revealed as compared with "passive" rats. The
      rats treated with galanin receptor antagonist showed a significant rise of serum
      corticosteron level immediately after forced swimming, while the control rats
      (without M-35) had only slight corticosterone increase under the sam conditions.
      The data obtained suggest involvement of brain galanin in formation of individual
      beha vior and indicate important role of galanin in coping with the stress.

PMID- 17216718
TI  - [Effects of dehydroepiandrosterone-sulfate on sexual motivation in male mice with
      different psychoemotional statuses].
AB  - Effects of dehydroepiandrosterone-sulfate (10, 30 and 100 microg/kg, i.p.) on
      stability of sexual motivation of C57BL/6J male mice with different
      psychoemotional statuses were studied. Sexual motivation was assessed for 30 min
      in the sensory contact setting: a male was exposed to a female at oestrus from
      behind a perforated transparent partition which prevented physical contact. In
      the intact males, dehydroepiandrosterone-sulfate injection (10 and 30 microg/kg)
      4 hrs before the test had no effect on parameters of sexual motivation. In
      aggressive males, administration of the dehydroepiandrosterone-sulfate had no
      effect on the intensity of the initial 10 min phase of sexual motivation but
      prevented its rapid decrease afterwards. In submissive mice, either dose reduced
      intensity of the initial phase of behavioral reaction to receptive female;
      however, tile higher dose prevented motivation from exhaustion, and so interest
      to the female was persistent, albeit decreased. The highest dose of
      dehydroepiandrosterone-sulfate had inhibitory effects on stability of the sexual
      interest in the male mice of all experimental groups.

PMID- 17216719
TI  - [The effect of prenatal stress on the carboxypeptidase H activity in the
      hypothalamo-pituitary-adrenal-gonadal system of the rat].
AB  - Effects of dams stress on the carboxypeptidase H: the neuropeptide exchange
      enzyme in the hypothalamo-pituitary-adrenall-gonadal system, was studied in the
      litter of different age (0, 14, 28, 45, and 120 day after birth) was studied. The
      sex differences in dynamic of enzyme activity in intact animals are
      substantiated. The effect of prenatal stress on carboxypeptidase H activity
      dependes on age and sex of animals. Prenatal stress is altering during the age
      dynamics of enzyme activity. This in the pituitary gland and hypothalamus of
      prenatal stressed female rats was a control for the male rats. In the adrenal and
      gonadal gland of prenatal stressed males, this was a control for the female rats
      female. The role of carboxypeptidase H in pubescence and mechanisms of effect of
      prenatal stress on sex system functional are discussed.

PMID- 17216720
TI  - [Role of V1- and V2-receptors in mechanism of physiological paradox--an increase
      of reabsorption of the solute free water and simultaneous rise of diuresis].
AB  - In experiments on non-anesthetized rats with administration into stomach of water
      (5 ml/100 g body mass) direct correlation has been found between an increase of
      diuresis and excretion of solute free water (r = 0.98, p < 0.01), while after
      injection to these animals of 5 x 10(-11) M arginine-vasotocin - between an
      increase of diuresis and simultaneous rise reabsorption of solute free water (r =
      0.8, p < 0.01). The rise of diuresis after the vasotocin injection is due to
      inhibition of sodium re- absorption, with the solute excretion fraction
      increasing from 2.6 +/- 0.2 % to 11.9 +/- 1.2, p < 0.001. A similar physiological
      paradox - an increase of diuresis with the simultaneous increase of reabsorption
      of solute free water - has been revealed at night hours in children with tendency
      for nocturnal enuresis (r = 0.64, p < 0.01). Mechanism responsible for this
      phenomenon consists in a rise of diuresis due to a decrease of sodium ion
      reabsorption in the ascending Henle loop limb. A problem is discussed of the
      homeostatic significance of a decrease of sodium reabsorption combined with an
      increase of solute-free water reabsorption; it is suggested that this phenomenon
      is based on a redistribution of reabsorption inside the nephron - a decrease of
      ion and water reabsorption in the initial parts of the nephron distal segment and
      an increase of solute free water reabsorption with the antidiuretic hormone
      stimulated high osmotic permeability of terminal parts of renal tubules. An
      intraperitoneal injection of V1-anatagonist (OPC-21268) decreased the natriuretic
      component of response to arginine-vasotocin, while injection of V2-antagonist
      (OPC-31260) eliminated the antidiuretic component.

PMID- 17216721
TI  - [The influence of protein starvation on hydrolytic and transport characteristics
      of the rat small intestine in chronic experiments].
AB  - Time dynamics of maltose, glycylglycine, glucose, and glycine hydrolysis and
      absorption in isolated loop of the small intestine was studied in chronic
      experiments on Wistar rats (group 1) after their transition from the standard
      diet to the protein-free one with enhanced content of carbohydrates. During
      protein starvation, there were different changes in the rates of glucose and
      glycine absorption, and glycylglycine hydrolysis and absorption in isolated
      intestinal loop, but to the end of the 2nd week they returned to the initial
      levels (for glucose and glycylglycine) or increased (for glycine). The rates of
      maltose hydrolysis and derived glucose absorption remained at the initial levels
      for the first days of protein starvation, decreased on the 5th day, and did not
      change afterwards. Maltase, alkaline phosphatase, and amino peptidase M
      activities, determined in homogenates of the small intestinal mucosa (per g of
      the tissue) after 2 weeks of protein starvation, were lower in the rats of group
      1 in comparison with the rats of group 2, kept on the standard diet. Thus, under
      protein deficiency the hydrolytic and absorptive capacities of the small
      intestine correspond to both ingested food composition, and body requirements.

PMID- 17216722
TI  - [Scent attractiveness and endocrine status in male students before and during a
      stress situation].
AB  - Scent attractiveness of sweat samples collected from male students before and
      during theoretical exams was assessed by female students. Five-rank scale was
      used for subjective assessment of the scent samples in term unpleasant/pleasant.
      Scent attractiveness depended on physiological conditions of both recipients and
      donors. Male students with low basal concentration of salivary cortisol smelt
      better than students with high level of cortisol. High level of salivary
      testosterone also was associated with low scent attractiveness of the male
      students, but only for the recipients in non-receptive phase of menstrual cycle.
      In all, the females who were in receptive phase of menstrual cycle assessed scent
      attractiveness of male students higher then the females in non-receptive phase.
      Exam stress coincided with increase of the salivary cortisol resulting in decline
      of scent attractiveness in male students. The negative effect of exam was most
      prominent in students that failed exam and in student who aspired to be the best
      but failed. So, the exam stress and basal variation of stress-related
      physiological indexes, such as salivary cortisol, are mirrored in male chemical
      signals, which are recognized by females.

PMID- 17216723
TI  - [Ca2+/calmodulin-dependent protein kinase II--a target for sodium valproate?].

PMID- 17216724
TI  - [Ivan Petrovich Pavlov and Harvey Williams Coushing].

PMID- 17216725
TI  - [Cerebral infarction after cocaine use].
AB  - Three relatively young patients, men aged 29 and 38 years and a woman aged 40
      years, developed ischaemic stroke shortly after cocaine use. All three had used
      cigarettes or alcohol as well, and suffered from neurologic deficits with CT and
      MRI lesions. They recovered, but neurologic sequelae remained. Cocaine may induce
      haemorrhagic as well as ischaemic stroke. Different vascular complications of
      cocaine may be involved. The pathophysiologic mechanisms of cocaine-induced
      ischaemic stroke include vasoconstriction due to cerebrovascular spasms and
      serotoninergic action, and enhanced thrombocyte aggregation. Over the last years,
      the use of cocaine is rising, so that the number of cocaine-related stroke
      patients can be expected to increase. Cocaine use as a cause of ischaemic stroke
      is important to recognise because discontinuation of cocaine can prevent a
      recurrent stroke.

PMID- 17216726
TI  - [The N-of-1 trial: the ideal study design that is underused].
AB  - The randomised experiment in a single patient, the N-of-1 trial, is the best
      study design for demonstrating causality, for example between agent and effect.
      Despite this, this type of study is only encountered sporadically in medical
      journals. One reason for this is that even this type of design cannot
      definitively demonstrate causality, because different points in time are compared
      with one another. Moreover, the design is rather inefficient, since the results
      correspond with those from observation without randomisation, placebo control or
      blinding. Even so, the N-of-1 trial is the ultimate form of verification in, for
      example, the individualisation of treatment. For this reason, this form of study
      might be used more often.

PMID- 17216727
TI  - [Restless legs due to ingestion of 'light' beverages containing saccharine;
      results of an N-of-1 trial].
AB  - OBJECTIVE: To determine whether there was a connection between the complaint of
      restless legs and the ingestion of artificial sweeteners in a patient with these
      symptoms after drinking certain 'light' beverages. DESIGN: Randomised, double
      blind, placebo-controlled N-of-1 trial with a cross-over design. METHOD: During a
      period of 48 days, the patient took 4 capsules per day containing either 150 mg
      of cyclamate, 22.5 mg of saccharine, both sweeteners, or placebo on two
      successive days. Between each of these 2-day periods there was a 2-day rest
      period during which no capsules were taken. The hospital pharmacist had prepared
      the capsules and determined the sequence of the 2-day periods on a random basis.
      The patient did not know which capsules he was taking. Every day on arising,
      starting 3 weeks before the trial period, the patient noted the intensity and
      duration of the symptoms in the late evening and previous night. For this
      notation he used an 11-point scale, from 0 (= no restless legs) to 10 (= almost
      total inability to sleep because of restless legs). RESULTS: A score of 1-3
      corresponded to mild symptoms that had no effect on the patient's sleep; at a
      score of 4-6 his sleep was disturbed and at a score of 7-10 the patient hardly
      slept at all. The patient had symptoms more often while using saccharine or the
      combination of saccharine and cyclamate than when taking the placebo (4 and 4
      versus 2 ofthe 6 nights); moreover, the average score was then statistically
      significantly higher (5.2 and 5.8 versus 3.3). CONCLUSION: There was a connection
      between the patient's complaints of restless legs and the use of saccharine, but
      not the use of cyclamate.

PMID- 17216728
TI  - [Acute abdomen caused by a large vesical cystine calculus].
AB  - A 73-year-old man underwent an emergency laparotomy because of acute abdominal
      pain and a palpable mass in the lower abdomen. A giant vesical calculus was found
      which had perforated the bladder, small intestine and sigmoid colon due to
      pressure necrosis. The stone had a length of 11.5 cm and weighed 1280 g. Further
      analysis revealed benign prostate hyperplasia, bladder diverticula and cystinuria
      as underlying causes. Initial therapy consisted of stone removal, partial bladder
      resection, a Hartmann procedure and partial resection of the small intestine.
      Secondarily, lifestyle advice was given and transurethral resection of the
      prostate followed later.

PMID- 17216729
TI  - [Bladder stones and lithotomy: a vanished ailment as the basis of urology].
AB  - Urinary bladder stones have played a role in medicine for ages. Many examples of
      this disease can be found in Dutch history. The need to cure this ailment led to
      the development of extremely painful interventions, for which self-appointed
      specialists very soon came forward and were then employed in this capacity in the
      cities. The various interventions were: perineal lithotomy using either the
      'apparatus minor' or the 'apparatus major', lateral lithotomy, cutting for stone
      'in two trips', suprapubic cystotomy, and ultimately lithotripsy. Bladder stones
      have largely disappeared from contemporary medicine and now represent only 5% of
      all urinary-tract stones, the main groups at risk being men with prostate
      hypertrophy, whether or not surgically treated, and women previously operated on
      for incontinence. Bladder stones are now seen mainly in developing countries. The
      dangerous operations via an extravesicular route have now been replaced by
      transurethral procedures in which the stone is disintegrated with the aid of an
      electric charge, shock waves or ultrasound. In an early stage, this ailment was
      the incentive for the development of a separate medical specialty: urology.

PMID- 17216730
TI  - [The 'Veenhuizen ophthalmia'].
AB  - In 1860 the institutions of the former Society of Welfare in Veenhuizen, the
      Netherlands, which had been taken over by the state, were struck by a mysterious
      eye disease. More than 5000 orphans and former beggars lived and worked in these
      institutions. The Minister of the Interior ordered an inquiry by the
      ophthalmologist Herman Snellen (1834-1908). He reported that the inmates slept in
      close proximity to one another and had to share dishes and towels. There was no
      clean water for washing or drinking. 788 (15%) people were found to be suffering
      from trachoma. On Snellen's advice, a start on improving the standards of hygiene
      was made but no more was done. The real reduction in prevalence came around 1900
      and was probably connected with a reduction of the number of inmates and
      improvements in hygiene.

PMID- 17216731
TI  - [The significance of Bernard Brouwer's contribution to Dutch neurology and
      neurosurgery. On the 125th anniversary of the year of his birth].
AB  - Following his training under Winkler and carrying out research at the Central
      Institute for Brain Research in Amsterdam, in 1923 Bernard Brouwer (1881-1949)
      became the firstprofessor ofneurologyindependent from psychiatry, in the
      Netherlands. His most important scientific work included comparative anatomical
      studies of the cerebellum and the projection of retinal fibres on the geniculate
      body and occipital cortex. He gained international fame and in 1926, during one
      of his American lecture tours, he was invited to fill the new chair of
      experimental neurology at Johns Hopkins University. He refused this offer and
      instead started a new university clinic for neurology in Amsterdam, which
      included neurosurgery. He did however send a surgeon--Dr. Oljenick--to America to
      be trained by Cushing. The Amsterdam neurology clinic became an international
      exchange centre for students of neuroscience. The difficult decisions he had to
      make during his rectorate in the Second World War, were criticised in 1945.
      During the last years of his life, he was director of the Central Institute for
      Brain Research.

PMID- 17216732
TI  - [The anamnesis in antiquity; medical questions by Rufus Ephesius (1st to 2nd
      century AD)].
AB  - Only one treatise devoted to medical history taking (anamnesis) has come down to
      us from antiquity: Medical questions by Rufus Ephesius (from about 80 to about
      150 AD). The work was rediscovered, published and translated from Greek into
      French by Daremberg and Ruelle in the 19th century. The word 'anamnesis' for
      history taking only came into use halfway through the 19th century in German
      speaking countries and in the Netherlands. The term was not used in this sense by
      physicians in antiquity. In contrast to several authors of the Corpus
      Hippocraticum (5th to 1st century BC), Rufus attached great importance to the
      interview with the patient and in particular to questions concerning the
      patient's lifestyle prior to the illness. In this respect, his opinions are
      remarkably close to modern views.

PMID- 17216733
TI  - [The Medical Code of Practice: clear reasons for existing, benefit less certain].
AB  - The Medical Code of Practice (Dutch acronym TG) aims to maintain and advance the
      quality of professional practice. Working together, lawyers and medical
      practitioners consider and make judgements on the procedures and methods
      practiced by caregivers. They also aim to protect citizens against the inexpert
      and careless execution of medical practice. Are they successful in this? Where
      the quality of practice is concerned, more thought must be given to the lasting
      effects on medical practitioners of the decisions made by the TG. Where
      protection ofcitizens is concerned, patients have a legal right to complain and
      there are various ways of doing this. Moreover, the TG is not primarily meant as
      a right of complaint. More empirical research is necessary into the effects of
      the TG.

PMID- 17216734
TI  - [Partial resistance to acenocoumarol and phenprocoumon caused by enzyme
      polymorphism].

PMID- 17216735
TI  - ['Multifactorial disorders in the genomics era'; notes on a recent report from
      The Royal Netherlands Academy of Arts and Sciences].

PMID- 17216737
TI  - Head and neck manifestations of Wegener's granulomatosis.
AB  - Wegener's Granulomatosis (WG) is a necrotizing granulomatous angiitis that
      presents the classic ELK triad of ear, nose, throat (E), lung (L), and kidney (K)
      involvement. Its potential rapid and fatal outcome makes the early recognition-
      before irreversible organ involvement occurs--mandatory. The aetiology is still
      unknown. Today, immunosuppressive therapy makes WG a treatable disease with a
      chronically relapsing course. The otorhinolaryngologist plays an important role
      in early diagnosis of WG, because in up to 95% of the patients initial WG
      symptoms are observed in the head and neck region. The majority of these patients
      show nasal or sinunasal involvement. Common manifestations are sinusitis,
      crusting of the nose, and development of saddle nose deformity. Other head and
      neck problems are middle and inner ear symptoms and subglottic stenosis. Follow
      up and activity assessment of the disease are also important roles to play for
      the otorhinolarygologist.

PMID- 17216738
TI  - Chronic inferior turbinate enlargement and the implications for surgical
      intervention.
AB  - Nasal obstruction due to chronic enlargement of the inferior turbinate is a
      common problem for the ENT surgeon. This review will discuss the pathology of
      'bilateral' and 'unilateral' turbinate enlargement associated with chronic
      rhinitis and nasal septal deviation, and focus on the structural changes in the
      turbinates. Cellular hyperplasia, tissue oedema and vascular congestion all
      contribute to turbinate enlargement, but there is some evidence that bony
      enlargement is associated with unilateral turbinate enlargement. There is no
      evidence for cellular hypertrophy despite the common use of the term 'turbinate
      hypertrophy' and this term should be replaced with the more correct term of
      'turbinate enlargement'. The underlying pathology of turbinate enlargement has
      important implications for the surgical management of nasal obstruction.

PMID- 17216739
TI  - Mechanical nasal alar dilators.
AB  - Most studies on nasal dilators have used Breathe Right or Nozovent. Both devices
      dilate the nasal valves, reduce nasal resistance, and improve nasal airflow. The
      use of dilators improves airflow most on inspiration, as the valve is stabilised
      and prevented from collapse. The response varies greatly between individuals, and
      can be impressive. The effect of nasal dilators may be lower in non-Caucasians.
      During exercise, nasal dilators delay the onset of oronasal breathing, and can
      have only small effects on performance thereafter. Nozovent and Breathe Right can
      reduce snoring, and improve otherwise obstructed breathing during sleep in
      selected patients. It is a challenge to find those patients, and one way could be
      to perform polysomnography with and without nasal dilator.

PMID- 17216740
TI  - Intracellular residency is frequently associated with recurrent Staphylococcus
      aureus rhinosinusitis.
AB  - AIM: The prevalence of intracellular Staphylococcus aureus organisms in the nasal
      mucosa of patients with recurrent infectious rhinosinusitis episodes was studied.
      METHOD: Twenty-seven consecutive adult patients who failed medical management of
      chronic rhinosinusitis (CRS) of multiple origins, associated or not with nasal
      polyposis, were consecutively enrolled for endonasal sinus surgery (including
      partial middle turbinectomy, middle antrostomy, ethmoidectomy, sphenoidotomy) and
      followed for a 12-month post-operative period. RESULTS: Seventeen of these
      patients showed the presence of intracellular S. aureus as detected by confocal
      laser scan immunofluorescence microscopy in epithelial cells of surgical
      intranasal biopsy specimens. Nine of the patients with and two without
      intracellular bacteria yielded S. aureus in endoscopically guided cultures of
      middle meatus secretions, despite the recent administration of prophylactic
      antibiotics. Eleven of the 17 patients with intracellular S. aureus relapsed for
      rhinosinusitis within the 12-month follow-up period. Molecular typing of
      sequential S. aureus isolates demonstrated the persistence of unique patient
      specific S. aureus clonotypes in nine of the patients with intracellular bacteria
      during the 12-month follow-up. CONCLUSION: The presence of intracellular S.
      aureus in epithelial cells of the nasal mucosa is a significant risk factor for
      recurrent episodes of rhinosinusitis due to persistent bacterial clonotypes,
      which appear refractory to antimicrobial and surgical therapy.

PMID- 17216741
TI  - A comparison between functional and radical sinus surgery in an experimental
      model of maxillary sinusitis.
AB  - PURPOSE OF THE STUDY: To compare functional and radical surgery in a maxillary
      sinusitis' treatment during in vivo experiments in rabbits. METHODS: An
      experimental chronic maxillary sinusitis was induced in 21 New Zealand white
      rabbits by inducing mucosal trauma combined with an injection of Streptococcus
      pneumoniae, and a maxillary sinus ostium occlusion during 28 days. Functional
      surgery (FS) by reopening the natural ostium and radical surgery (RS) by
      reopening the natural ostium were performed in association with removal of the
      sinus mucosa. They were macroscopically and histologically evaluated 15 days, 1
      month and 2 months after the surgery. RESULTS: FS had diminished chronic
      inflammatory criteria (lymphoid and plasma cells) faster that RS ([15 days (p =
      0.016)]; [1 month (p = 0.03)]; [2 months (p = 0.03)]). Mucosa fibrosis was more
      important after RS ([15 days (p = 0.016)]; [1 month (p = 0.03)]; [2 months (p =
      0.016)]). CONCLUSION: FS accelerates healing with less fibrosis that RS in
      pathological mucosa altered by a chronic inflammation.

PMID- 17216742
TI  - Submucosal glands and goblet cells in maxillary sinus surgery: an experimental
      study in rabbits.
AB  - HYPOTHESIS: After sinus surgery poor ciliary activity and disorders in mucus
      production can lead to an increase in postoperative complications. PURPOSE OF
      THIS STUDY: To evaluate the changes in the ultrastructure of submucosal glands
      (SG) and goblet cells (GC) after partial or wide surgical removal of maxillary
      sinus mucosa (MSM). METHODS: Twenty New Zealand White rabbits were divided in two
      groups of 10 animals. In group A, the mucosa of the right maxillary sinus (MS)
      was removed. In contrast, in group B only a strip the mucosa around the ostium
      was removed. After three months the sinus were opened and the mucosa studied by
      light-, and scanning- and transmision electron microscopy. RESULTS: After three
      months in group A all right MS were infected with purulent secretions, and the
      density of SG with a mean value of 10.4 per mm, standard deviation (SD) 3.36 and
      GC 81.81 per mm (SD: 3.82). However, in group B the SG were 52.3 per mm (SD: 4.5)
      and GC 4.45 per mm (SD: 1.23). These results were statistically significant (p <
      0.001). Histopathological findings showed in group A, after three months, SG with
      a fewer number of microvilli in the glandular lumen.

PMID- 17216743
TI  - Respiratory adenomatoid hamartoma must be suspected on CT-scan enlargement of the
      olfactory clefts.
AB  - OBJECTIVE: To demonstrate that Respiratory Epithelial Adenomatoid Hamartoma
      (REAH) of the nose, a recently individualized benign tumour, is characterized by
      a significant widening of the CT-scan width of the olfactory clefts. PATIENTS AND
      METHODS: Retrospective study comparing, in the axial and coronal planes, the CT
      scan maximum width of the olfactory clefts, i.e. the maximum distance between
      both turbinal ethmoidal walls, of 15 REAH patients, 36 Nasal Polyposis (NPS) and
      49 normal individuals. RESULTS: In axial and coronal planes, respectively, the
      medians of the olfactory clefts width were of 12.2 mm and 12.1 mm for REAH, and
      5.6 mm and 5.4 mm for NPS, compared to 4.5 mm and 4.2 mm for normal individuals
      (both p < 0.0001). Total nasal width (i.e. the distance between both medial
      orbital walls) was not found to be different between groups in both planes. The
      median ratios "olfactory cleft width/total nasal width" were, for the axial and
      coronal planes respectively, of 53.1% and 44.7 for REAH, and 23.5% and 22.9% for
      NPS, compared to 19.2% and 19.1% for normal controls (both p < or = 0.001).
      CONCLUSION: Compared to normal and nasal polyposis CT-scans, REAH significantly
      enlarges the olfactory clefts width. Bilateral REAH represent a genuine
      differential diagnosis of Nasal Polyposis; the CT-scan appears as a major clue to
      differentiate the two diseases. Endoscopic surgery of REAH definitely confirms
      their origin in the olfactory cleft, and opens a new field of endoscopic surgery
      of the olfactory cleft.

PMID- 17216744
TI  - "Post-nasal drip syndrome": most patients with purulent nasal secretions do not
      complain of chronic cough.
AB  - INTRODUCTION: Post-nasal drip syndrome (PNDS) is quoted as a common cause of
      chronic cough. However, there is little evidence to explain the mechanism by
      which PNDS may stimulate the cough reflex. This cohort study looks at patients
      with purulent nasal secretions, who may best represent any potential candidate
      for PNDS, and observes the frequency of symptomatic coughing. METHODS: One
      hundred and eight consecutive patients referred to a rhinology clinic with
      symptoms of chronic infective rhinosinusitis, all with purulent nasal secretions
      identified on nasendoscopy, were observed through investigation and treatment.
      Patients were initially treated with broad-spectrum antibiotics and nasal
      douching. The frequency of coughing was recorded pre- and post- treatment.
      RESULTS: Eighty-nine percent of patients complained of post-nasal secretions.
      Twenty-three (21%) patients complained of cough. Eight had co-existing asthma, 3
      had bronchiectasis, 1 had sarcoid and 2 had had a recent respiratory tract
      infection. Therefore 9 patients (8%) had purulent nasal secretions and a cough
      with no other discernable pathology. Cough improved in 8 of the 9 patients
      following treatment. Cough improved in 9 of the 14 patients with other possible
      co-existing causes for cough. CONCLUSIONS: Only a small proportion of patients
      with purulent rhinosinusitis without coexisting chest disease complain of cough.
      Although nasal disease may be a genuine cause for chronic cough it is unlikely to
      be as common a cause as has been reported. Postnasal secretions do not appear to
      be an adequate cause for cough and the term 'PNDS' should be replaced by
      rhinosinusitis when nasal disease is the cause of chronic cough.

PMID- 17216745
TI  - Phenylpropanolamine's decongestive effect on the nasalmucosa of pregnant women
      with nasal stuffiness.
AB  - Pregnancy rhinitis is common and very troublesome for many women. Today, no safe
      and effective treatment is available for this condition. The aim of this placebo
      controlled double-blind study was to evaluate the decongestive effect of
      phenylpropanolamine (PPA 50 mg) twice daily for seven days in 38 women with
      pregnancy rhinitis. In the morning, before starting the course of treatment, and
      two to three hours after taking the last dose of the study-medicine in the
      morning on the eighth day, recordings of the position of the nasal mucosal
      surface were made with rhinostereometry. Every evening, the women filled in a
      questionnaire about their symptoms on a scale from 0-9 (0 = no symptoms, 9 =
      extremely severe symptoms). The effects of the drug on their blood pressure and
      other side-effects were also determined. The patients used a newly-evaluated
      telephone method to assess their daily symptoms. PPA 50 mg had a decongestive
      effect on the nasal mucosa, as measured with symptom scores and rhinostereometry.
      In the placebo group, this effect was found with rhinostereometry, but not on
      nasal stuffiness as judged by the symptom scores. The reason why the placebo
      group also experienced a decongestive effect after treatment may have been due to
      stress because the patients were in a hurry and such stress may have a
      decongestive effect on the nasal mucosa. No effects on the blood pressure or
      other side-effects were detected. In conclusion, this study shows that PPA 50 mg
      twice daily may be an effective and safe treatment in pregnancy rhinitis.

PMID- 17216746
TI  - Male subjects who could not perceive the pheromone 5a-androst-16-en-3-one,
      produced similar orbitofrontal changes on PET compared with perceptible
      phenylethyl alcohol (rose).
AB  - BACKGROUND: The aim of this study was to evaluate in how far cerebral blood flow
      changes in male subjects when exposed to a pheromone that they cannot consciously
      smell. METHODS: We used a boar taint steroid (5a-Androst-16-en-3-one), which is
      similar to human axillary sweat but could not be detected by the human volunteers
      who participated in this study. RESULTS: The pheromone produced activation of the
      orbitofrontal and frontal cortex in comparison to a baseline condition. The same
      regions were activated when the subjects smelled a rose-like odour. CONCLUSION:
      This study shows that a pheromone, which is not consciously detected, can evoke a
      response in the brain that is similar to a detectable odour.

PMID- 17216748
TI  - Susceptibility weighted imaging (SWI).

PMID- 17216747
TI  - The prevalence of allergic rhinitis in adults in Aydin, Turkey.
AB  - BACKGROUND: Allergic rhinitis is the most common allergic disease in Turkey. Our
      objective was to determine the prevalence of allergic rhinitis among adults
      living in Aydin, Turkey. METHODS: A population-based survey was undertaken among
      adults aged 16-64 years. Allergic rhinitis was confirmed in the subjects screened
      positive by the clinical examination and specific immunoglobulin E testing.
      RESULTS: A total of 465 interviews were conducted in spring 2005. The prevalence
      of allergic rhinitis in the past 12 months was 14.0%. The prevalence rate of
      clinically confirmable AR was computed as 11.4%. The prevalence was significantly
      higher among females and in urban areas. Specific IgE were detected for at least
      one of tested aeroallergens in 34.8% of the subjects with self-reported AR.
      CONCLUSION: Our study revealed that the prevalence of allergic rhinitis among
      adults living in the city of Aydin was as high as the prevalence in other regions
      of Turkey but less than in Europe.

PMID- 17216750
TI  - [Field perturbations by magnetic dipoles as a model for magnetically labelled
      cells in MRI].
AB  - Due to the creation of intense local magnetic fields, iron oxide nanoparticles
      are used as a contrast agent to produce signal loss in Magnetic Resonance Imaging
      (MRI) in regions where labelled cells have migrated. OBJECTIVE: To study effects
      of the intracellular distribution of magnetic moments on the extracellular
      magnetic field by means of numerical simulations. METHODS: Various geometries of
      intracellular particle distributions were scrutinized and the extracellular field
      distortions were computed. The total magnetic moment of a labelled cell was
      assigned to various magnetic subcompartments. The implications on the intravoxel
      frequency distribution and the static MR signal decay were assessed. RESULTS: The
      extracellular field perturbation was affected by the intracellular particle
      distribution only in close proximity to the labelled cell. With increasing
      distance from the labelled cell, the effects of the intracellular particle
      distribution were less pronounced. The intravoxel frequency distribution induced
      by a single labelled cell was non-lorentzian. CONCLUSION: The magnetic fields
      created by an iron loaded cell are sensitive to the intracellular distribution of
      nanoparticles only in close proximity to the cell. Far from the cell the field
      perturbation cannot be distinguished from the magnetic dipole field produced by a
      magnetic sphere with the same total magnetic moment.

PMID- 17216749
TI  - Susceptibility weighted imaging: data acquisition, image reconstruction and
      clinical applications.
AB  - Susceptibility-weighted imaging (SWI) is a novel method, that combines magnitude
      and phase information from a high-resolution, fully velocity compensated 3D T2
      weighted gradient echo sequence. Phase images are unwrapped and high pass
      filtered to highlight phase changes associated with venous vessels and converted
      into a mask that is multiplied with the corresponding phase image. This technique
      has been applied thus far to the imaging of tumors, vascular malformations,
      trauma, stroke, micro-hemorrhages, and as a functional imaging method. The
      purpose of this paper is to present an overview of the current status of the
      technique and to illustrate its potential.

PMID- 17216751
TI  - Demonstration of paramagnetic and diamagnetic cerebral lesions by using
      susceptibility weighted phase imaging (SWI).
AB  - Susceptibility-weighted MR imaging (SWI) has become a non-invasive diagnostic
      modality for functional MR imaging (fMRI) of the brain and also for the imaging
      of tumors, injuries, malformations or microhemorrhages. SWI often enables
      detection of otherwise subtle abnormalities or provides additional relevant
      information when combined with routine MR imaging. The purpose of this article is
      to illustrate the potential of SWI in the discrimination of paramagnetic and
      diamagnetic brain lesions in neuroradiological applications.

PMID- 17216752
TI  - Contrast enhanced susceptibility weighted imaging (CE-SWI) of the mouse brain
      using ultrasmall superparamagnetic ironoxide particles (USPIO).
AB  - Susceptibility weighted imaging (SWI) has been introduced as a novel approach to
      visualize the venous vasculature in the human brain. With SWI, small veins in the
      brain are depicted based on the susceptibility difference between
      deoxyhaemoglobin in the veins and surrounding tissue, which is further enhanced
      by the use of MR phase information. In this study we applied SWI in the mouse
      brain using an exogenous iron-based blood-pool contrast agent, with the aims of
      further enhancing the susceptibility effect and allowing the visualization of
      individual veins and arteries. Contrast enhanced (CE-) SWI of the brain was
      performed on healthy mice and mice carrying intracerebral glioma xenografts. This
      study demonstrates that detailed vascular information in the mouse brain can be
      obtained by using CE-SWI and is substantially enhanced compared to native SWI
      (i.e. without contrast agent). CE-SWI images of tumour-bearing mice were directly
      compared to histology, confirming that CE-SWI depicts the vessels supplying and
      draining the tumour. We propose that CE-SWI is a very promising tool for the
      characterization of tumour vasculature.

PMID- 17216753
TI  - [Testing of model assumptions of MR oxygen extraction fraction mapping using a
      phantom study].
AB  - Oxygen supply is an important parameter for the evaluation of tissue viability
      and therefore of high interest in cancer diagnosis and therapy. One promising
      approach to extract relevant information from imaging data is the determination
      of oxygen saturation by means of the BOLD-effect. Using a simple model of tissue
      structure allows to evaluate the susceptibility difference between tissue and
      venous blood, from which the blood oxygen extraction fraction can be derived
      indirectly. The present study tested the validity of two model assumptions needed
      for exact quantification: the independence of the results of both capillary
      diameter d and the relative blood volume lambda. For this purpose a phantom was
      built, which allows the evaluation of susceptibility differences depending on d
      (27 microm-238 microm) and lambda (3%-12%). In agreement with model assumptions,
      delta chi(lambda) was widely constant and independent of ) lambda. In
      contradiction to the model, delta chi (d) showed a positive slope (delta chi
      range: 0.35-0.57 ppm). The present study suggests that the simple model
      investigated here has shortcomings in the quantification of oxygen extraction due
      to insufficient model assumptions.

PMID- 17216754
TI  - Deformable registration for image-guided radiation therapy.
AB  - Ths paper examines several applications of deformable registration algorithms in
      the field of image-guided radiotherapy. The first part focuses on the description
      of input and output of deformable registration algorithms, with a brief review of
      conventional and most current methods. The typical applications of deformable
      registration are then reviewed on the basis of four practical examples. The first
      two sets of examples deal with the fusion of images obtained from the same
      patient (inter-fraction registration), with time intervals of several days
      between each image. The other two examples deal with the fusion of images
      obtained in immediate sequence (intra-fraction registration); in this case, the
      focus is the displacement during image acquisition or patient treatment (mainly
      due to respiratory movement), with time intervals in the order of magnitude of
      tenths of seconds. Finally, the registration of images of different patients
      (inter-patient registration) is also discussed. In conclusion, deformable
      registration has become a fundamental tool for image analysis in radiotherapy.
      Although extensive validation of the numerous existing methods is required before
      extending its clinical use, deformable registration is expected to become a
      standard methodology in the treatment planning systems in the near future.

PMID- 17216755
TI  - PSF, LSF and S/P in mammography: GEANT4 validation.
AB  - The main goal of this study was to validate the predictions of GEANT4, a Monte
      Carlo code originally developed for high-energy physics, for low-energy (10-40
      keV) photon transmission and scattering through matter similar to biological
      tissue. We compared GEANT4 calculations with existing phantom data relevant for
      the mammographic imaging technique. This work showed that scattered-to-primary
      ratio data can be simulated using GEANT4 with a deviation smaller than 5%. At the
      same time, we encountered a limitation in the small-angle region description by
      the code, which is important for point- and line-spread function calculations.
      The comparison with forward angle data showed that the GEANT4 models, known as
      "G4 Low Energy" and "G4 Penelope", describe the measurements for X-ray beams
      typically used in mammography better than 10% for angles above 10 degrees, and
      that "G4 Low Energy" is preferable to "G4 Penelope ". The results confirm the
      possible use of GEANT4 for the optimization of applications based on low-energy
      photon transmission and scattering.

PMID- 17216756
TI  - Application of the inverse Monte Carlo treatment planning system IKO for an
      inhomogeneous dose prescription in the sense of dose painting.
AB  - Biological imaging (PET SPECTJfMRI, MRS, etc.) is able to provide tri-dimensional
      biological information, i.e. proliferation, cell density, hypoxia or
      choline/citrate ratio. The implementation of this information in a treatment plan
      can be utilised to escalate the dose in target subvolumes. For this purpose, a
      treatment planning system has to be able to realise an inhomogeneous dose
      prescription with sufficient spatial resolution. The present study investigated
      to which extent the inverse Monte Carlo treatment planning system IKO (inverse
      kernel optimization), developed at our department, can modulate an inhomogeneous
      dose prescription. As a qualifier to describe this ability, we defined in analogy
      to imaging a modulation transfer function for treatment planning systems. In
      addition two clinical cases, a prostate case and a head-and-neck case, were set
      up with different dose prescriptions in different subtargets. The modulation
      transfer function revealed that IKO is able to modulate structures larger than
      1.3 cm with sharp dose gradients. Also, IKO is able to modulate several
      subtargets inside a prostate with different escalated doses. The dose-volume
      histograms of the head-and-neck case showed a good dose coverage of the target
      volumes, as well as a good protection of the organs at risk according to the dose
      constraints. As a result, IKO is able to realise a heterogeneous dose
      prescription in the sense of "dose painting".

PMID- 17216757
TI  - Evaluation of a commercial electron treatment planning system based on Monte
      Carlo techniques (eMC).
AB  - A commercial electron beam treatment planning system on the basis of a Monte
      Carlo algorithm (Varian Eclipse, eMC V7.2.35) was evaluated. Measured dose
      distributions were used for comparison with dose distributions predicted by eMC
      calculations. Tests were carried out for various applicators and field sizes,
      irregular shaped cut outs and an inhomogeneity phantom for energies between 6 Me
      V and 22 MeV Monitor units were calculated for all applicator/energy combinations
      and field sizes down to 3 cm diameter and source-to-surface distances of 100 cm
      and 110 cm. A mass-density-to-Hounsfield-Units calibration was performed to
      compare dose distributions calculated with a default and an individual
      calibration. The relationship between calculation parameters of the eMC and the
      resulting dose distribution was studied in detail. Finally, the algorithm was
      also applied to a clinical case (boost treatment of the breast) to reveal
      possible problems in the implementation. For standard geometries there was a good
      agreement between measurements and calculations, except for profiles for low
      energies (6 MeV) and high energies (18 Me V 22 MeV), in which cases the algorithm
      overestimated the dose off-axis in the high-dose region. For energies of 12 MeV
      and higher there were oscillations in the plateau region of the corresponding
      depth dose curves calculated with a grid size of 1 mm. With irregular cut outs,
      an overestimation of the dose was observed for small slits and low energies (4%
      for 6 MeV), as well as for asymmetric cases and extended source-to-surface
      distances (12% for SSD = 120 cm). While all monitor unit calculations for SSD =
      100 cm were within 3% compared to measure-ments, there were large deviations for
      small cut outs and source-to-surface distances larger than 100 cm (7%for a 3 cm
      diameter cut-out and a source-to-surface distance of 10 cm).

PMID- 17216758
TI  - The ergonomic conundrum for technology integration.
AB  - In the operatory of today, the opportunities are great. Space is at a premium and
      integration is a must. By consolidating the operator's primary supplies, which
      formerly were spread around the room, performance improves and space is gained
      for the successful introduction of high technology. Room cost decreases,
      permitting more networked rooms in less space at a lower cost. The productive
      potential of today's practice is greater than ever before; however, to gain the
      most from these opportunities, a change must occur in our perception of the
      treatment environment. When designing an office for the coming decades, it is
      vitally important to create a space for the future, not the past. Dentists must
      be willing to look objectively at their clinical environment and be willing to
      gain a clear sense of future needs. Your new treatment room can become a tool for
      future growth and prosperity or a museum about dentistry's past. Opportunity
      knocks.

PMID- 17216759
TI  - Digital esthetic connection.

PMID- 17216760
TI  - Choose to be the village dentist.

PMID- 17216761
TI  - Integrating digital radiography: from diagnostic input to procedure guidance.

PMID- 17216762
TI  - My experience with reality-based consultation and treatment planning.

PMID- 17216763
TI  - Effective website promotion.

PMID- 17216765
TI  - Secure network computing and communications.

PMID- 17216764
TI  - The erbium laser: the "Star Wars" of dentistry.

PMID- 17216766
TI  - Discovering the ClikRay system.

PMID- 17216767
TI  - Safer shift work through more effective scheduling.

PMID- 17216768
TI  - Virtual search and rescue.

PMID- 17216769
TI  - Safety identification 101.

PMID- 17216770
TI  - Handling a wider range of threats.

PMID- 17216771
TI  - Construction's ever-changing hazards.

PMID- 17216772
TI  - Saving money by becoming a highly protected risk.

PMID- 17216773
TI  - 'There was an accident at work, but I'm ok'.

PMID- 17216774
TI  - Step by step.

PMID- 17216775
TI  - Lifesaving success results in updated AED/CPR guidelines.

PMID- 17216776
TI  - AED, CPR, and first aid preparedness for the real world.

PMID- 17216777
TI  - Medical management guidelines for unidentified chemicals.

PMID- 17216778
TI  - Flammable liquids: what can you do with them?

PMID- 17216780
TI  - Payment. Forestalling cuts.

PMID- 17216781
TI  - Patient safety. Stop yelling at me.

PMID- 17216783
TI  - Payment. Financial aid.

PMID- 17216782
TI  - Infection control. They need to know.

PMID- 17216784
TI  - Payment. Closures imagined.

PMID- 17216785
TI  - Compliance. Tracking dollars.

PMID- 17216786
TI  - Staffing. Back to school.

PMID- 17216787
TI  - Staffing. Candy striper redux.

PMID- 17216789
TI  - Wall St. discovers quality.

PMID- 17216788
TI  - Data page. Staffing woes, ambulance diversions lead to longer ED wait times.

PMID- 17216790
TI  - The see-through hospital.
AB  - Health care providers are under the gun to become more transparent on everything
      from quality to prices to charity care. But just what transparency entails,how
      the information is used and who benefits are anything but clear. Advocates say it
      will improve quality, control costs and lead to a dearer understanding of
      community benefits.

PMID- 17216791
TI  - The wow--and the now.

PMID- 17216792
TI  - Improving patient throughput.

PMID- 17216793
TI  - Hassle-free consulting.

PMID- 17216794
TI  - Back-to-basics measures save lives. Interview by John DiConsiglio.

PMID- 17216796
TI  - Climbing construction cost.

PMID- 17216795
TI  - Defining & measuring community benefit.

PMID- 17216797
TI  - Executive dialogue series. Performance improvement in the era of quality
      improvement.

PMID- 17216798
TI  - Ten common mistakes that keep patients from using your hospital's Web site--and
      10 solutions.

PMID- 17216799
TI  - Making a difference. Honoring rural hospital executives who have improved the
      health status of their communities.

PMID- 17216800
TI  - Weinberg's differential rule reconsidered.
AB  - A central problem in research on twins is the estimation of the rates of
      monozygotic and dizygotic twin maternities. The estimation usually follows
      Weinberg's differential rule. According to this rule, the rate of dizygotic
      twinning is twice the rate of twin maternities in which the twins are of opposite
      sex. The monozygotic twinning rate is the difference between the rates of same
      sex and opposite-sex twin sets. Weinberg's differential rule is implicitly based
      on the assumptions that the probability of a male equals the probability of a
      female and that the sexes in a dizygotic twin set are independent. Although
      Weinberg's differential rule has been the target of continuing discussions, the
      reliability of these assumptions has never been conclusively verified or
      rejected. In this study we present new variance formulas for the monozygotic and
      dizygotic twinning rates obtained using Weinberg's differential rule and stress
      that these new formulas have to be used. We analyze the accuracy of Weinberg's
      differential rule by considering alternative attempts. Especially, we build a
      general likelihood function and show that the maximum-likelihood estimates differ
      only slightly from the rates obtained using Weinberg's differential rule. In
      addition, our methods are applied to twinning data from Finland and Sweden. We
      compare our results with findings in the literature. In conclusion, our findings
      indicate that Weinberg's differential rule is rather robust and that despite its
      simplicity, it gives reliable results when official birth registers are analyzed.

PMID- 17216801
TI  - Combining genetics and population history in the study of ethnic diversity in the
      People's Republic of China.
AB  - Genomic data have increasingly been used to complement linguistic, archeological,
      and anthropological evidence in reconstructing the origins and migratory patterns
      of modern humans. East Asia is a particular hotspot of human migration,
      especially mainland China, where a large number of human fossils have been
      unearthed and more than 20% of the world's population now resides. There are 56
      officially recognized ethnic populations (minzu) in China. In the present study
      we investigated the ancestry and genetic diversity of nine populations: the
      majority Han of Liaoning Province; the Miao, Yao, Kucong, and Tibetan communities
      of Yunnan Province in southwest China; and four Muslim populations, the Hui,
      Bonan, Dongxiang, and Sala from central and northern China. We used both
      biparental and uniparental markers to determine patterns of diversity at
      autosomal, mitochondrial, and Y-chromosome loci. The study populations displayed
      several paternal origins but restricted maternal ancestries. From the Y
      chromosome data in particular, major demographic changes, such as the Neolithic
      population expansion and more recent historical events including migration along
      the Silk Road, could be inferred. Specific aspects of the internal structure and
      organization of the study populations, including endogamy and consanguinity, were
      uncovered using autosomal markers. However, we encountered interpretive problems
      in terms of the definition of the present-day ethnic study populations in China,
      which appear to reflect past and present political as well as genetic influences.

PMID- 17216802
TI  - Opportunity for natural selection and gene flow in an isolated Zapotec-speaking
      community in southern Mexico in the throes of a secular increase in size.
AB  - Our object in this paper is to analyze the opportunity for natural selection and
      gene flow in an isolated Zapotec-speaking community in the valley of Oaxaca,
      southern Mexico, that is undergoing a secular increase in body size. Surveys were
      conducted in the community in 1968, 1978, and 2000, including anthropometric and
      census data. No secular change was found in the growth status of schoolchildren
      and adult height between 1968 and 1978; subsequently, major secular gains in
      height occurred among children and adolescents between 1978 and 2000. The 1978
      household data were used to compute gene flow (3.3%) and opportunity for
      selection intensity (I = 1.312). Migration and other demographic information was
      obtained from household census data for 1978 and 2000, and mortality information
      was extracted from community records and archives. These data were used to
      compute gene flow and opportunity for natural selection. Gene flow increased from
      3.3% to 4.7% and intensity of natural selection decreased from 1.312 to 0.272
      from 1978 to 2000. Variance in fertility increased slightly over time (12.25 to
      13.69). Opportunity for selection was dominant during the prereproductive period
      in 1978, but approached 0 for the mortality component in 2000, resulting in a
      marked decrease in the mortality component (Im) of selection (0.626 and 0.019,
      respectively) and total opportunity for selection (I = 1.312 and 0.272,
      respectively). Secular increase in height and markedly decreased opportunity for
      natural selection (1) were associated with better health and nutritional
      conditions. Genotype-environment interaction and environmental influences are
      apparently the predominant causes of the secular trend. If natural selection
      plays a role in causing the secular trend, it is a small one.

PMID- 17216803
TI  - North African Berber and Arab influences in the western Mediterranean revealed by
      Y-chromosome DNA haplotypes.
AB  - We have analyzed Y-chromosome diversity in the western Mediterranean area,
      examining p49a,f TaqI haplotype V and subhaplotypes Vb (Berber) and Va (Arab). A
      total of 2,196 unrelated DNA samples, belonging to 22 populations from North
      Africa and the southern Mediterranean coast of occidental Europe, have been
      typed. Subhaplotype Vb, predominant in a Berber population of Morocco (63.5%),
      was also found at high frequencies in southern Portugal (35.9%) and Andalusia
      (25.4%). The Arab subhaplotype Va, predominant in Algeria (53.9%) and Tunisia
      (50.6%), was also found at a relatively high frequency in Sicily (23.1%) and
      Naples (16.4%); its highest frequency in Iberia was in northern Portugal (22.8%)
      and Andalusia (15.5%). In Iberia there is a gradient of decreasing frequencies in
      latitude for both subhaplotypes Va and Vb, related to eight centuries of Muslim
      domination (8th to 15th centuries) in southern Iberia.

PMID- 17216804
TI  - Pleiotropic QTL on chromosome 12q23-q24 influences triglyceride and high-density
      lipoprotein cholesterol levels: the HERITAGE family study.
AB  - To determine whether a common quantitative trait locus (QTL) influences the
      variation of fasting triglyceride (TG) and high-density lipoprotein cholesterol
      (HDL-C) levels, we used a bivariate multipoint linkage analysis with 654
      polymorphic markers in 99 white and 101 black families. The phenotypes were
      investigated under two conditions: at baseline and after a 20-week exercise
      training intervention. A maximum genome-wide bivariate LOD score of 3.0 (p =
      0.00010) was found on chromosome 12q23-q24, located within the IGF1 gene (insulin
      like growth factor 1, at 107 cM) for TG and HDL-C at baseline in whites. This
      bivariate linkage peak is considerably higher than the univariate linkage results
      at the same chromosome location for either trait (for TG, LOD = 2.07, p =
      0.00108; for HDL-C, LOD = 2.04, p = 0.00101). The genetic correlations between
      baseline TG and HDL-C levels were -0.14 for the residual and -0.33 for the QTL
      components. Moreover, association analysis showed that TG, HDL-C, and IGF1 are
      significantly associated (p = 0.04). In conclusion, these results suggest that a
      QTL on chromosome 12q23-q24 influences the variation of plasma TG and HDL-C
      levels. Further investigation should confirm whether IGF1 or another nearby gene
      is responsible for the concomitant variation in TG and HDL-C levels.

PMID- 17216805
TI  - A locus on chromosome 13 influences levels of TAFI antigen in healthy Mexican
      Americans.
AB  - When activated, thrombin activatable fibrinolysis inhibitor (TAFI) inhibits
      fibrinolysis by modifying fibrin, depressing its plasminogen binding potential.
      Polymorphisms in the TAFI structural gene (CPB2) have been associated with
      variation in TAFI levels, but the potential occurrence of influential
      quantitative trait loci (QTLs) located elsewhere in the genome has been explored
      only in families ascertained in part through probands affected by thrombosis. We
      report the results of the first genome-wide linkage screen for QTLs that
      influence TAFI phenotypes. Data are from 635 subjects from 21 randomly
      ascertained Mexican American families participating in the San Antonio Family
      Heart Study. Potential QTLs were localized through a genome-wide multipoint
      linkage scan using 417 highly informative autosomal short tandem repeat markers
      spaced at approximately 10-cM intervals. We observed a maximum multipoint LOD
      score of 3.09 on chromosome 13q, the region of the TAFI structural gene. A
      suggestive linkage signal (LOD = 2.04) also was observed in this region, but may
      be an artifact. In addition, weak evidence for linkage occurred on chromosomes
      17p and 9q. Our results suggest that polymorphisms in the TAFI structural gene or
      its nearby regulatory elements may contribute strongly to TAFI level variation in
      the general population, although several genes in other regions of the genome may
      also influence variation in this phenotype. Our findings support those of the
      Genetic Analysis of Idiopathic Thrombophilia (GAIT) project, which identified a
      potential TAFI QTL on chromosome 13q in a genome-wide linkage scan in Spanish
      thrombophilia families.

PMID- 17216806
TI  - Multiple QTLs influence variation in paraoxonase 1 activity in Mexican Americans.
AB  - Paraoxonase 1 (PON1), a high-density-lipoprotein-associated enzyme known to
      protect against cellular damage from toxic agents, may also have antioxidant
      properties. Although the importance of the influence of the PON1 structural locus
      on chromosome 7q21-22 for variation in the concentration and activity of the
      enzyme is well-documented, the contribution of other loci is poorly understood.
      Based on the recent observations of at least one additional quantitative trait
      locus (QTL) for PON1 activity in pedigreed baboons, we conducted a whole-genome
      linkage screen for QTLs other than the PON1 structural locus that may influence
      PON1 activity in humans. We measured PON1 activity in frozen serum for 1,406
      individuals in more than 40 extended pedigrees from the San Antonio Family Heart
      Study (SAFHS). We used a maximum-likelihood-based variance decomposition approach
      implemented in SOLAR to test for QTLs that may influence PON1 activity. In
      addition to a QTL for which we detected the strongest, significant evidence (LOD
      = 31.41) at or near the PON1 structural locus on chromosome 7q21-22, we also
      localized at least one additional significant QTL on chromosome 12 (LOD = 3.56).
      Furthermore, we detected suggestive evidence for two more PON-related QTLs on
      chromosomes 17 and 19. We have provided evidence that other genes, in addition to
      the well-known ones on chromosome 7, play a role in influencing normal variation
      in PON1 activity.

PMID- 17216807
TI  - Radiographic joint space of the knee in healthy young adults.
AB  - The primary objective of this study was to characterize normal variation in
      radiographic joint space of the knee in a large sample of healthy young adults
      and to identify factors that contribute to this variation. We measured
      radiographic knee joint space in 279 skeletally mature subjects, age between 16
      and 22 years, who participated in the Fels Longitudinal Study. Minimum joint
      space was measured in the medial and lateral knee compartments. Independent
      sample t tests and correlation analyses were performed to examine sex differences
      and associations between joint space, joint size, and body size [weight, stature,
      body mass index (BMI)]. Results show that young men have thicker articular
      cartilage than young women in both the medial and lateral compartments of the
      knee. Significant positive correlations were found between joint space and body
      size measures in the total sample. When the sexes were considered independently,
      however, correlations between joint space and body size were significant in men
      only. Regression analyses of the combined-sex sample identified sex, BMI, and
      joint width as significant explanatory factors of medial joint space, together
      accounting for 26% of the observed variance. In contrast, sex was the sole
      significant explanatory factor of lateral joint space, explaining 19% of the
      observed variance. Results of this study show that during early adulthood, when
      articular cartilage is healthy and at its peak thickness, men have thicker knee
      cartilage than women. At this young age body size accounts for a modest
      proportion of the variation observed in knee cartilage thickness.

PMID- 17216808
TI  - Effect of ACP1*C on early life viability.
AB  - Associations with past malarial morbidity, season of conception, and common
      diseases such as obesity, type 2 diabetes, and allergy argue against neutrality
      of the ACP1 genetic polymorphism. Comparison of ACP1 distribution in mothers and
      their newborns and analysis of the joint wife-husband ACP1 phenotype distribution
      in couples with repeated spontaneous abortion suggest a negative effect of the
      ACP1*C allele on early life viability. Analysis of the polymorphism of the ACP1
      gene suggests that, unlike the ACP1*A and ACP1*B alleles, the ACP1*C allele is
      independent of sequences in the 5' flanking region, resulting in an inverted F/S
      isoform ratio.

PMID- 17216809
TI  - Further data on a 9.1-kb insertion-deletion polymorphism: survey of Mediterranean
      populations.
AB  - We report the distribution of a previously described 9.1-kb insertion-deletion
      polymorphism located on chromosome 22. We analyzed 1,844 individuals sampled from
      26 Mediterranean populations in mainland Italy, Sicily, Sardinia, Tunisia, Libya,
      Morocco, Egypt, Greece, and Albania. The 9.1 kb - allele is the prevalent allele
      in the North African (range, 0.53-0.56), Greek (0.51), and Albanian (0.66)
      populations, whereas the 9.1 kb + allele is most frequent in a mainland Italian
      town (0.55) and in all Sicilian and Sardinian towns and villages thus far tested,
      with marked fluctuation ranges of 0.53-0.78 and 0.56-0.80, respectively. In tests
      for Hardy-Weinberg equilibrium the genotype frequencies observed in Athens and in
      four of the nine towns in Sicily (but in none of the towns in Sardinia) departed
      highly significantly from the expected values. Identical results were found in
      the same towns for a second insertion-deletion polymorphism located on chromosome
      22ql13 at a distance compatible with a low incidence of recombination. The data,
      which are in good agreement with the different histories of the two islands
      (Sardinia and Sicily), are consistent with a west-east differentiation in Sicily
      and support the evidence for ancient gene flow from the Iberian peninsula to
      Sardinia.

PMID- 17216810
TI  - A profile of female academic surgeons: training, credentials, and academic
      success.
AB  - The objective of this study was to determine the profile (credentials, training,
      and type of practice) of female academic general surgeons and factors that
      influenced their career choice. A survey was sent to female academic surgeons
      identified through general surgery residency programs and American medical
      schools. The women had to be Board eligible/certified by the American Board of
      Surgery or equivalent Board and have an academic appointment in a Department of
      Surgery. Data were analyzed using the SPSS program. Two hundred seventy women
      (age range, 32-70 years) completed the survey (98.9% response rate). Fellowships
      were completed by 82.3 per cent (223/270), most commonly in surgical critical
      care. There were 134 (50.2%, 134/367) who had two or more Board certificates,
      most frequently (46%, 61/134) in surgical critical care. Full-time academic
      appointments were held by 86.7 per cent of women, most as assistant professors,
      clinical track; only 12.4 per cent were tenured professors. The majority of women
      described their practice as "general surgery" or "general surgery with emphasis
      on breast." The most frequent administrative title was "Director." Only three
      women stated that they were "chair" of the department. The top reason for
      choosing surgery was "gut feeling," whereas "intellectual challenge" was the
      reason they pursued academic surgery. When asked "Would you do it again?", 77 per
      cent responded in the affirmative. We conclude that female academic surgeons are
      well trained, with slightly more than half having two or more Board certificates;
      that most female academic surgeons are clinically active assistant or associate
      professors whose practice is "general surgery," often with an emphasis on breast
      disease; that true leadership positions remain elusive for women in academic
      general surgery; and that 77 per cent would choose the same career again.

PMID- 17216811
TI  - Profile of female academic general surgeons.

PMID- 17216812
TI  - Profile of female academic surgeons.

PMID- 17216813
TI  - Utility of neurosurgical consultation for mild traumatic brain injury.
AB  - Trauma patients presenting with a Glasgow Coma Scale (GCS) score of 14-15 are
      considered to have mild traumatic brain injury (TBI) with overall good neurologic
      outcomes. Current practice consists of initial stabilization, followed by a head
      CT, and neurosurgical consultation. Aside from serial neurologic examinations,
      patients with a GCS of 15 rarely require neurosurgical intervention. In this
      study, we examined the added value of neurosurgical consultation in the care of
      patients after TBI with a GCS of 15. We retrospectively reviewed the medical
      records of patients presenting after blunt trauma with an abnormal head CT and
      GCS of 15 between January 2004 and January 2005. Patients with a normal head CT
      and <48 hours hospital stay were excluded. Data included demographics, mechanisms
      of injury, Injury Severity Score, the radiologists' dictated interpretations of
      the head CT, and neurosurgical interventions. Fifty-six patients met the
      inclusion criteria. The mean age was 41+/-2.3 years, and the mean Injury Severity
      Scores was 10.2 +/-0.6. Mechanisms of injury included 64 per cent motor vehicle
      crash, 16 per cent motorcycle crash, 13 per cent fall, and 7 per cent all-terrain
      vehicle crash. The initial CT scans showed 43 per cent parenchymal contusions, 38
      per cent subarachnoid hemorrhage, 14 per cent subdural hematomas, and 5 per cent
      epidural hematomas. All patients received a routine follow-up head CT, and 16 per
      cent showed changes (five improved and four were worse compared with initial CT
      scans). None of these patients received a neurosurgical intervention, and two
      were transferred to a rehabilitation service. In this era of limited resources,
      trauma patients who present with a GCS score of 15 after mild TBI can be safely
      managed without neurosurgical consultation, even in the presence of an abnormal
      head CT scan.

PMID- 17216814
TI  - The effect of bacterial contamination on neointimal hyperplasia in vascular
      grafts.
AB  - Neointimal hyperplasia (NH) is the most significant contributing factor to long
      term vascular graft failure. Inflammation is known to be important in its
      development; however, the role of bacterial infection is unclear. We examined the
      effect of contamination with common organisms on the development of NH in
      expanded polytetrafluoroethylene grafts. Thirty adult pigs were randomized into
      one of four groups: no infection, contamination with Staphylococcus aureus, mucin
      producing Staphylococcus epidermidis, or Pseudomonas aeruginosa. An expanded
      polytetrafluoroethylene graft (6 mm x 3 cm) was placed as a common iliac artery
      interposition graft and was inoculated with 1-2 x 10(8) of the selected organism
      before closure. Grafts were explanted 6 weeks postoperatively. Microbiologic,
      histological, and morphometric evaluations were performed. All grafts were patent
      at the time of euthanasia. The mean areas of NH were 5.45 mm(2) in sterile
      grafts, 8.36 mm(2) in S. aureus, 7.63 mm(2) in S. epidermidis, and 11.52 mm(2) in
      P. aeruginosa grafts. Comparison of means via analysis of variance showed that P.
      aeruginosa grafts had significantly higher formation of NH than sterile grafts (P
      = 0.025). NH production in infected grafts appears to be organism specific and is
      significantly higher with P. aeruginosa than common Gram-positive organisms.
      Increased NH from subclinical infection may be a significant factor contributing
      to late graft failures.

PMID- 17216815
TI  - Didactic surgical education by faculty: the effect on American Board of Surgery
      In-Training examination percentile scores.

PMID- 17216816
TI  - Acellular dermal allograft for ventral hernia repair in the compromised surgical
      field.
AB  - A ventral hernia and a contaminated surgical field are a difficult surgical
      combination. We hypothesize that acellular human dermis (AHD) can be a suitable
      biological tissue alternative in the repair of a ventral hernia. The study
      involved a retrospective review of the use of AHD in the repair of ventral hernia
      from 2001-2004. Inclusion criteria included a ventral hernia repair in a clean
      contaminated (CC) or contaminated-dirty (CD) surgical field. The primary outcome
      of the study was wound infection and mesh removal. Patients were stratified into
      CC and CD, and management of a wound infection [medically managed (MM) or
      surgically managed (SM)]. Seventy-five patients met the study criteria. The most
      common comorbidity was hypertension (45.3%). There was one death in the study
      (from multiple organ dysfunction syndrome). The overall wound infection rate was
      33.3 per cent: 11 MM (14.7%) and 14 SM (18.7%). The average length of stay was
      16.7 days (+/-20.8) with a mean follow-up of 275 (+/-209) days. Subgroup
      analysis: CC (n = 64) had 9 wound infections that were MM (14.1%) and 12 wound
      infections that were SM (18.8%); CD (n = 11) had 2 wound infections that were MM
      (18.2%) and 2 wound infections that were SM (18.2%). Five of 14 SM (35.7%) wound
      infections required removal of the mesh. Wound infection in the contaminated
      surgical field occurred 33.3 per cent of the time. Some (18.7%) of the cases
      required SM management, and 35.7 per cent of these required removal of the AHD.

PMID- 17216817
TI  - Differential expression of prognostic factors and effect on survival in young (<
      or =40) breast cancer patients: a case-control study.
AB  - The belief that young women develop more aggressive forms of breast cancer than
      other women is controversial. The purpose of this study was to determine if women
      40 years of age and under with breast cancer have more negative prognostic
      indicators and a higher 5-year mortality than those women over 40 years of age.
      From January 1998-December 2002, all women with breast cancer were identified
      from our tumor registry. Women with metastatic disease at presentation were
      excluded from our study. The women were divided into two groups, women under 40
      (cases) and women 40 and over (controls). Seventy-eight cases were identified and
      matched to 228 controls. These cohorts were matched 3:1 (cases:controls) based on
      tumor staging. The data collected on each patient included prognostic factors
      such as tumor size, tumor type, estrogen and progesterone receptors, Her2/neu,
      and Ki-67. Information on surgical procedure, postoperative therapy, recurrence,
      and mortality was also gathered. The mean ages for cases and controls were 35 and
      59 years, respectively. The rates of modified radical mastectomy were similar in
      the two groups, but young women were more likely to have breast reconstruction
      (33.7% vs 9.8%). The rates of breast conservation therapy were actually lower in
      the group under 40 (32.5% vs 37.6%). Tumors in the 40 and under group were more
      frequently estrogen receptor negative (33.8% vs 21.9%: P = 0.046) and
      progesterone receptor negative (50.0% vs 35.5%: P = 0.033). Younger women also
      experienced a greater prevalence of Ki-67 (P < 0.001) and higher levels of
      Her2/neu overexpression (P = 0.013). Women over 40 were more likely to receive
      hormonal therapy (39.7% vs 36.1%). Women over 40 had a lower overall rate of
      recurrence. A difference in overall survival does exist between these two groups
      of women, which trends toward significance. The women 40 and under had a lower
      overall 5-year survival. The reason for this difference remains unclear. Although
      we demonstrate a higher percentage of younger women with negative biochemical
      markers, the only factors independently and significantly related to higher
      mortality were estrogen receptor negativity and tumor stage at presentation.

PMID- 17216818
TI  - Incidence of vitamin deficiency after laparoscopic Roux-en-Y gastric bypass in a
      university hospital setting.
AB  - Vitamin deficiency after gastric bypass surgery is a known complication. The
      purpose of this study was to measure the incidence of vitamin deficiency after
      laparoscopic Roux-en-Y gastric bypass in a university hospital setting. All
      patients who underwent laparoscopic Roux-en-Y gastric bypass from January 2002 to
      December 2004 and completed a 1- and 2-year follow-up after surgery were
      selected. Of the total 493 patients, 318 (65%) had vitamin results at 1-year
      follow-up. Of the 366 eligible for the 2-year follow-up, 141 (39%) had vitamin
      results. Patients were further grouped based on gender, race, and Roux limb
      length, and incidence of vitamin deficiencies were studied. The incidence of
      vitamin A (retinol) deficiency was 11 per cent, vitamin C was 34.6 per cent,
      vitamin D25OH was 7 per cent, vitamin B1 was 18.3 per cent, vitamin B2 was 13.6
      per cent, vitamin B6 was 17.6 per cent, and vitamin B12 was 3.6 per cent 12
      months after surgery. There was no statistical difference in the incidence of
      vitamin deficiencies between 1 and 2 years. In univariate and multivariate
      logistic regression of 1- and 2-year follow up, black patients (vitamins A, D,
      and B1 for 1 year and B1 and B6 for 2 years) and women (vitamin C at 1 year) were
      more likely to have vitamin deficiencies. Vitamin deficiencies after laparoscopic
      Roux-en-Y gastric bypass are more common and involve more vitamins, even those
      that are water soluble, than previously appreciated. Black patients tend to have
      more deficiencies than other groups. The bariatric surgeon should be committed to
      the long-term follow-up and care of these patients. Further prospective and
      randomized studies are necessary to provide appropriate guidelines for
      supplementation.

PMID- 17216820
TI  - Migrating mesh mimicking colonic malignancy.
AB  - The use of prosthetic mesh is the current acceptable standard for the repair of
      hernias. Recurrence rate has been greatly reduced since Lichtensen in 1986 first
      described mesh repair of inguinal hernias. The most common complication arising
      from inguinal hernia repair even with mesh is recurrence. There are isolated
      reports of migrated mesh in the three decades of mesh use in hernia repair. We
      present a case report of a migrated mesh plug presenting with features highly
      suggestive of an intra-abdominal neoplasm in a 63-year-old man who presented with
      weight loss, anorexia, fatigue, and a palpable right lower quadrant mass. Work up
      had revealed a large inflammatory mass involving the cecum and not amenable to
      percutaneous or colonoscopic biopsy, thus requiring diagnostic laparoscopy. He
      had a right inguinal hernia repair with mesh 8 years earlier. At diagnostic
      laparoscopy, an extensive right lower quadrant mass involving the cecum, bladder,
      and transverse colon and extending to the midline was found, necessitating
      conversion to open laparotomy and a right hemicolectomy. A mesh plug was found
      intimately involved with the specimen. Plugs used in inguinal hernia repair
      rarely migrate. It is rarer still for them to present as a possible colonic mass.
      This is the first known case report of mesh plug migration presenting as a
      suspected colonic malignancy.

PMID- 17216819
TI  - Intra-abdominal placement of antimicrobial-impregnated mesh is associated with
      noninfectious fever.
AB  - The antimicrobial, silver/chlorhexidine, when impregnated on mesh has been
      demonstrated to resist mesh infection in in vitro and in vivo models. The
      clinical, human systemic response to intraperitoneal placement of
      silver/chlorhexidine-impregnated mesh has not been investigated to date. Between
      October 2002 and November 2004, all in-patients undergoing laparoscopic ventral
      hernia repair were retrospectively analyzed. All repairs used expanded
      polytetraflouroethylene (ePTFE) Dual Mesh (DM) or ePTFE impregnated with
      silver/chlorhexidine, Dual Mesh Plus (DM+). Patient demographics, hernia
      characteristics, mesh type, operative details, and hospital course data were
      collected. Noninfectious fevers were defined as a temperature greater than 100.4
      F without an identified source. Standard statistical methods were used. During
      the 2-year study period, 120 patients underwent laparoscopic ventral hernia
      repair (DM = 55, DM+ = 65). The two groups were similarly matched in terms of
      age, body mass index, American Society of Anesthesiologists score, defect size,
      and mesh size. Postoperative fever without an identified source occurred in 10
      (18.2%) patients with DM and in 25 (38.5%) patients using DM+ (P = 0.015). A
      multivariant analysis revealed that only mesh type and body mass index predicted
      postoperative fever. All fevers resolved within the first 72 hours in the DM
      patients; however, 16 per cent of the DM+ group had persistent fevers of unknown
      origin after 72 hours. Within the DM+ group, patients with postoperative fevers
      had significantly longer postoperative stays (4.8 days vs 3.0 days; P = 0.009).
      The use of antimicrobial-impregnated ePTFE mesh with silver/chlorhexidine in
      laparoscopic ventral hernia repair is associated with noninfectious postoperative
      fever. In our patients, the evaluation and management of these fevers resulted in
      a significantly longer hospital stay.

PMID- 17216821
TI  - Sequential linear stapling technique for perineal resection of intractable
      pediatric rectal prolapse.
AB  - Rectal prolapse (RP), although most frequently encountered in the frail elderly,
      may also occur in children. This condition is most troublesome in the premature
      infant with significant associated comorbidities. Pediatric RP most often can be
      managed conservatively with expectant and/or judicious use of laxative-based
      bowel regimens. In rare instances of intractable RP, surgical intervention
      ranging from simple (sclerotherapy, Thiersch wire) to complex (perineal or
      transabdominal bowel resection) becomes necessary. We describe a modification of
      the Altemeier technique using a novel sequential linear stapling technique to
      treat intractable RP in a 5.0-kg infant with severe coexisting life-threatening
      comorbidities. The child had resumption of bowel movements on postoperative Day 1
      and has had no recurrences. Sequential linear stapling technique for perineal
      resection of intractable pediatric RP appears to be a safe and potentially
      attractive alternative.

PMID- 17216822
TI  - Small bowel obstruction by wireless enteroscopic capsule and unrecognized
      intestinal stricture.
AB  - The wireless enteroscopy capsule (WEC) was approved for noninvasive visualization
      of small bowel. We report an unusual case of a previously healthy man with
      history of bowel resection and anastomosis who developed small bowel obstruction
      after ingestion of a WCE. At operation, an anastomotic stricture site was noted
      and the WEC was proximal to this stricture, causing obstruction. This case
      emphasizes the importance of a good history and physical examination, as well as
      vigilant follow-up and retrieval of WEC.

PMID- 17216823
TI  - Intestinal obstruction in pregnancy: a case of small bowel volvulus and review of
      the literature.

PMID- 17216824
TI  - Laparoscopic-assisted percutaneous endoscopic gastrostomy: its role in providing
      enteric access when percutaneous endoscopic gastrostomy is not possible.
AB  - Percutaneous endoscopic gastrostomy (PEG) replaced open surgical gastrostomy
      (OSG) as the preferred method for enteric access soon after its introduction in
      1980. Since that time, laparoscopic gastrostomy (LG), percutaneous radiologic
      gastrostomy (PRG), and laparoscopic-assisted PEG (LAPEG) have been introduced.
      PEG and PRG have been found to be over 95 per cent successful, convenient,
      economical, and associated with less morbidity than OSG. However, there are
      patients that are not appropriate candidates for, or have failed attempts at, PEG
      or PRG placement. At one time, OSG was the only option left for these patients,
      but they may be better served by LAPEG or, in some cases, LG. LAPEG offers less
      morbidity than OSG by having less pain and wound complications, and potentially
      may avoid the use of general anesthesia. We present a series of patients that
      underwent successful LAPEG placement after an unsuccessful attempt at PEG
      placement, and we describe its role in patient care.

PMID- 17216825
TI  - Hypoglycemia in the setting of advanced gastrointestinal stromal tumor.
AB  - We report a rare case of symptomatic hypoglycemia in a patient with intra
      abdominal recurrence of a previously resected gastrointestinal stromal tumor
      (GIST). The patient is a 65-year-old woman who underwent resection of a large
      abdominal mass arising from the stomach, histologically diagnosed as a high-grade
      leiomyosarcoma. She was lost to follow up. Five years later, the mass recurred;
      core biopsy demonstrated a CD 117-positive, spindle-cell tumor, consistent with a
      GIST. She was placed on Gleevec, as there was evidence of multifocal disease, but
      imaging revealed only mild improvement. Subsequently, her clinical status
      deteriorated, and she was hospitalized for dehydration, vomiting, and mental
      status changes. Her blood glucose on admission was 22 mg/dL, and a dextrose
      infusion (50%) was necessary to maintain adequate blood glucose levels.
      Measurements of insulin, proinsulin, c-peptide, beta-hydroxybutyrate, and thyroid
      stimulating hormone were normal, as were cosyntropin stimulation and glucagon
      response tests. Suspicions arose for tumor-secreted insulin-like factor. She
      underwent resection of the dominant 44-cm recurrence, with immediate rebound
      hyperglycemia, followed by complete normalization of her blood glucose levels.
      She was discharged on postoperative Day 5 without symptoms or insulin, and is
      alive with disease at 20 months. Paraneoplastic syndromes occur in only 15 per
      cent of patients with known malignancies (e.g., lung cancer and metastatic
      carcinoid), and are rarely reported in the setting of GIST. Hypoglycemia is most
      often observed in presence of insulinoma and only isolated case reports in GIST
      patients exist. Overexpression of insulin-like growth factor II is thought to be
      the mechanism of action. Supportive management and palliative resection or
      debulking is recommended when possible.

PMID- 17216826
TI  - Is surgical thrombectomy to salvage failed autogenous arteriovenous fistulae
      worthwhile?
AB  - The Dialysis Outcomes Quality Initiatives guidelines emphasize placement of
      autogenous arteriovenous (AV) fistulae for patients on hemodialysis. This
      recommendation is based on studies that demonstrate enhanced patency for AV
      fistulae compared with grafts. However, closer review of the data demonstrates
      that although primary patency of AV fistulae is superior to grafts, the secondary
      patency rates are equivalent. This suggests that secondary procedures to maintain
      fistula patency are inferior to those performed on arteriovenous grafts. Surgical
      thrombectomy of AV fistulae can be challenging. It is often difficult to
      completely remove thrombus adjacent to the anastomosis of the fistula, and
      pseudoaneurysms within the fistula can prevent passage of the thrombectomy
      catheter and complete removal of thrombus from the fistula. Consequently, some
      surgeons simply abandon thrombosed AV fistulae and place a new access. We have
      developed a method for completely clearing thrombus from failed AV fistulae by
      locating the fistulotomy close to the arterial anastomosis and using a technique
      to manually extract thrombus from the fistula before passing a thrombectomy
      catheter. The purpose of this study was to review our results with this
      procedure. Between 2001 and 2004, 10 patients with a previously functioning AV
      fistula presented with thrombosis. There were seven brachiocephalic fistulae and
      three radiocephalic fistulae. All patients underwent surgical thrombectomy and
      fistulography. Five patients underwent balloon angioplasty of a venous stenosis
      and one patient underwent surgical revision of an arterial stenosis. Technical
      success, defined as being able to completely clear thrombus from the fistula and
      treat the cause for fistula failure, was achieved in 70 per cent (7/10) of cases.
      Technical failure was caused by vein rupture during the balloon angioplasty in
      two cases and a central venous occlusion that could not be treated in one case.
      The 6-month primary and secondary patency for cases that were technically
      successful was 51 and 69 per cent, respectively. Our conclusion was that surgical
      thrombectomy can significantly extend fistula functionality in patients who
      present with thrombosis.

PMID- 17216827
TI  - Hypocalcemia after neck exploration for untreated primary hyperparathyroidism.
AB  - Hypocalcemia after neck exploration for hyperparathyroidism is an important
      postoperative management issue. With increasing acceptance of less invasive
      surgical approaches, hypocalcemia is less frequent. This study was conducted to
      evaluate postoperative hypocalcemia after current surgical exploration techniques
      in patients with untreated primary hyperparathyroidism. From the University of
      Louisville parathyroid database, charts of patients undergoing surgery for
      untreated primary hyperparathyroidism from May 1, 1998 to May 30, 2004 were
      reviewed. Data was analyzed based on age, sex, preoperative calcium and
      parathyroid hormone levels, preexisting diseases, and extent of neck exploration.
      One hundred sixty-nine patients were identified with adequate data for analysis.
      Transient postoperative hypocalcemia occurred in 21 per cent (36/169) for the
      total group, in 18 per cent (22/125) after minimally invasive radio-guided
      parathyroidectomy, and in 32 per cent (14/44) after bilateral neck exploration.
      Patients with postoperative hypocalcemia had a statistically significant
      association with older age and pre-existing hypertension. Patients with
      postoperative hypocalcemia were more likely to have undergone longer surgical
      procedures and were more likely to have had pre-existing diabetes and mental
      disorders. These findings were not statistically significant and were considered
      trends. The frequency of osteoporosis in the hypocalcemia group was increased but
      was not significant. Transient hypocalcemia occurred in 21 per cent of patients
      after parathyroid surgery. It was more likely after bilateral neck exploration, a
      longer duration of surgery, and with hypertension, diabetes, and mental
      disorders.

PMID- 17216828
TI  - Utility of liver function tests after laparoscopic cholecystectomy.
AB  - Many surgeons routinely obtain liver function tests (LFTs) after all laparoscopic
      cholecystectomies. Others argue that LFTs provide no useful information and add
      time and expense to the patient's hospitalization. This purpose of this study was
      to determine if routine postoperative LFTs predict complications. One hundred
      ninety-nine consecutive patients undergoing laparoscopic cholecystectomy were
      included in the analysis. Nine (4.5%) patients had postoperative complications:
      eight with retained common bile duct stones and one with a cystic duct stump
      leak. All were diagnosed with postoperative endoscopic retrograde
      cholangiopancreatography. Only four of the nine patients had hyperbilirubinemia.
      Overall, 39 patients had postcholecystectomy hyperbilirubinemia, with four (10%)
      patients having complications (three retained stones and one had a bile leak).
      For the entire study population, there was no difference between pre- and
      postoperative total bilirubin and aspartate aminotransferase levels (0.6 vs 0.6
      mg/dL; P = 0.623 and 25 vs 41 U/L; P = 0.111, respectively). There was a
      statistically significant difference in pre- and postoperative alanine
      aminotransferase and alkaline phosphatase (31 vs 50 U/L; P = 0.003 and 95 vs 90
      U/L; P = 0.001, respectively). Postoperative elevations in liver function tests
      are frequently seen after laparoscopic cholecystectomy. These elevations do not
      predict postoperative complications. LFTs should be obtained only when clinically
      indicated.

PMID- 17216830
TI  - Anti-HIV agents. Switching therapy may help reverse body shape changes.

PMID- 17216829
TI  - Ischemic proctitis: case series and literature review.
AB  - Ischemic injury to the rectum is rare owing to its rich vascular supply, and is
      seldom seen in clinical practice. Risk factors include major vascular occlusive
      disease, disruption of collateral circulation, and low flow state. It is of
      paramount importance to diagnose this entity early in its course. Although CT
      scan can suggest the diagnosis and identify other causes of clinical
      deterioration, colonoscopy remains the key test in diagnosing and determining the
      extent of ischemic change. Endoscopic findings and the overall clinical picture
      determine patient management. Treatment is nonoperative for nongangrenous
      ischemic proctocolitis, whereas surgery is necessary for gangrenous, transmural
      rectal ischemia. Over a 20-year period, a retrospective review of cases of acute
      rectal ischemia were analyzed. Aortoiliac occlusive disease accounted for nearly
      one-half the cases (7/15), and 40 per cent (6/15) was secondary to a low flow
      state. In our series, two-thirds of the cases involved transmural necrosis of the
      rectal wall (40% mortality) and the remaining one-third presented with patchy
      ischemic changes (20% mortality).

PMID- 17216831
TI  - Anti-HIV agents. Danish study finds survival with HAART similar to some HIV
      negative people.

PMID- 17216832
TI  - Report from the 5th International Workshop on Pharmacology.

PMID- 17216833
TI  - Anti-HIV agents. Hepatitis C treatment and possible interactions with anti-HIV
      drugs.

PMID- 17216835
TI  - Anti-HIV agents. Nelfinavir levels during pregnancy.

PMID- 17216834
TI  - Anti-HIV agents. The puzzle of virologic failure with tenofovir.

PMID- 17216836
TI  - Anti-HIV agents. Unexpected results from a tipranavir study.

PMID- 17216837
TI  - Anti-HIV agents. A protease-only regimen--Kaletra and saquinavir.

PMID- 17216839
TI  - Anti-HIV agents. Is it age or AIDS? Study finds risk of dementia increases with
      age.

PMID- 17216838
TI  - Anti-HIV agents. No interaction between tenofovir and saquinavir.

PMID- 17216840
TI  - Anti-HIV agents. Unexpected impact of HAART on depression in some women with
      HIV/AIDS.

PMID- 17216842
TI  - Nutrition. Long-term high-dose carnitine found to help heal damaged nerves.

PMID- 17216841
TI  - Tests. Study explores the consequences of viral load "blips".

PMID- 17216843
TI  - Report from the 4th International Workshop on Clinical Pharmacology of HIV
      Therapy. Introduction.

PMID- 17216844
TI  - Report from the 4th International Workshop on Clinical Pharmacology of HIV
      Therapy. Nevirapine levels in the blood found higher in women.

PMID- 17216845
TI  - Report from the 4th International Workshop on Clinical Pharmacology of HIV
      Therapy. Drinking lots of water still necessary with new indinavir regimens.

PMID- 17216846
TI  - Report from the 4th International Workshop on Clinical Pharmacology of HIV
      Therapy. Checking up on ddI and tenofovir in people with HIV/AIDS.

PMID- 17216847
TI  - Report from the 4th International Workshop on Clinical Pharmacology of HIV
      Therapy. Drug levels in PHAs who receive liver transplants.

PMID- 17216848
TI  - Report from the 4th International Workshop on Clinical Pharmacology of HIV
      Therapy. New formulation of nelfinavir on the way.

PMID- 17216849
TI  - Report from the 4th International Workshop on Clinical Pharmacology of HIV
      Therapy. Does Roche's nelfinavir cause less diarrhea?

PMID- 17216850
TI  - Anti-HIV agents. Atazanavir as a booster for protease inhibitors.

PMID- 17216851
TI  - Immune boosters. Murabutide--debut of a new immune booster?

PMID- 17216852
TI  - Nutrition. Complementary therapies in Ontario.

PMID- 17216854
TI  - Anti-HIV agents. The future of drug therapy.

PMID- 17216853
TI  - Anti-cancer agents. Unique protocol looks promising for lymphoma.

PMID- 17216855
TI  - Anti-HIV agents. Alternating regimens look promising.

PMID- 17216856
TI  - Anti-HIV agents. Drug holidays.

PMID- 17216857
TI  - Anti-HIV agents. An attempt at treatment interruption--trial CPCRA 064.

PMID- 17216858
TI  - Anti-HIV agents. Can immune boosters prolong the time away from HAART?

PMID- 17216859
TI  - Anti-HIV agents. Introduction to ICAAC: selected highlights from the 43rd annual
      Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

PMID- 17216860
TI  - Anti-HIV agents. Trying times for tenofovir and abacavir.

PMID- 17216861
TI  - Anti-HIV agents. Abacavir--as good as AZT?

PMID- 17216862
TI  - Anti-HIV agents. Abacavir only once-daily.

PMID- 17216864
TI  - Nutrition. Study finds vitamin B12 levels low in some HAART users.

PMID- 17216863
TI  - Anti-HIV agents. High-dose vitamin C may affect indinavir users.

PMID- 17216865
TI  - Anti-HIV agents. A warning about high viral loads.

PMID- 17216866
TI  - Anti-HIV agents. Dying without ever having received treatment in Canada.

PMID- 17216867
TI  - Anti-HIV agents. Study finds recovery of CD4+ cells may be less than expected.

PMID- 17216868
TI  - Infection fighters. Valtrex suppresses herpes outbreaks.

PMID- 17216869
TI  - Infection fighters. High-dose Valtrex for oral hairy leukoplakia.

PMID- 17216871
TI  - EC extends ban on imports of captive live birds.

PMID- 17216870
TI  - Travel-related thrombosis: is this a problem?

PMID- 17216872
TI  - Veterinary medicines and owner compliance.

PMID- 17216873
TI  - Concerns about improper use of anthelmintics.

PMID- 17216874
TI  - ["The heroine who opposed the Teutonic armed forces with the great loving soul of
      a Russian woman"].

PMID- 17216875
TI  - Better lipid profile for Invirase.

PMID- 17216876
TI  - Intracranial hemorrhage with Aptivu.

PMID- 17216878
TI  - [Adolf Hitler: "our strategy is to defeat the enemy from within"].

PMID- 17216877
TI  - [About our losses suffered in the battles at Rzhev and Vyazma].

PMID- 17216879
TI  - [Briansk partisans].

PMID- 17216880
TI  - Damage control surgery for the patient who has experienced multiple traumatic
      injuries.
AB  - PATIENTS WHO HAVE EXPERIENCED multiple traumatic injuries present one of the
      greatest challenges for perioperative teams. IN A TRAUMA PATIENT who is
      hemorrhaging, increased risk of death arises from a vicious cycle of hypothermia,
      coagulopathy, and metabolic acidosis known as the triad of death. A STAGED
      SURGICAL APPROACH predicated on specific priorities for treating multiply injured
      patients can help save the lives of these patients.

PMID- 17216881
TI  - Toxic anterior segment syndrome--more than sterility meets the eye.
AB  - TOXIC ANTERIOR SEGMENT SYNDROME (TASS) is a rare, potentially devastating
      complication of routine intraocular surgery that occurs when a noninfectious
      toxic agent enters the anterior segment of the eye, causing an inflammatory
      reaction. SEVERE CASES OF TASS can cause permanent harm, and if symptoms still
      are present after six weeks, the eye is not likely to recover. EARLY DIAGNOSIS
      AND TREATMENT are effective in preventing permanent damage, but often TASS is
      mistakenly diagnosed as infectious endophthalmitis for which treatment is
      completely different. THE CAUSES AND TREATMENT of TASS are discussed, and risk
      reduction strategies are described.

PMID- 17216882
TI  - [Brandy (palinka) consumption in Debrecen in the 18th and early 19th centuries].

PMID- 17216884
TI  - [N.I. Pirogov: "one has to tell the truth" - the celebrated military surgeon
      worked for many years on the Medical Council of the Ministry of the Interior].

PMID- 17216883
TI  - [Military dentists in the service of the fatherland].

PMID- 17216885
TI  - [Death and Comenius's praxis pietatis].

PMID- 17216886
TI  - Constructing census families and classifying households: "relationship to head of
      family or household" in the 1901 census of Canada.

PMID- 17216887
TI  - Integrating Canadian and U.S. historical census microdata: Canada (1871 and 1901)
      and the United States (1870 and 1900).

PMID- 17216889
TI  - Analysis of household samples: the 1901 census of Canada.

PMID- 17216888
TI  - [Sexual division of revolutionary work: reflections on the Salvadorean
      experience, 1970-94].

PMID- 17216890
TI  - The Canadian families project and the 1901 census.

PMID- 17216891
TI  - Joseph Ewan (1909-1999): a retrospective.

PMID- 17216892
TI  - Joseph Andorfer Ewan (1909-1999).

PMID- 17216893
TI  - Stress, obesity, and the metabolic syndrome: soul and metabolism.

PMID- 17216894
TI  - IEEE Visualization Conference and IEEE Symposium on Information Visualization
      Proceedings 2006. October 29-November 3, 2006. Baltimore, Maryland, USA.

PMID- 17216895
TI  - Cognitive-behavioral interventions for IV insertion pain.
AB  - INSERTION OF AN IV CATHETER is a commonly performed and painful procedure. The
      use of cognitive-behavioral interventions (CBIs) may decrease pain by diverting
      the patient's attention to stimuli other than pain. THIS RANDOMIZED, CONTROLLED
      TRIAL examined the effect of three CBIs--music, kaleidoscope, and guided imagery-
      on IV insertion pain in 324 patients. NO STATISTICALLY SIGNIFICANT differences in
      IV insertion pain were found among the treatment and control groups or between
      choosing versus being assigned a CBI. Insertion attempts were more difficult in
      women, and insertion difficulty was correlated with pain intensity and pain
      distress. Pain intensity was related to insertion site and catheter gauge.

PMID- 17216896
TI  - Clean hands, healing hands: an unorthodox presentation.

PMID- 17216897
TI  - Chronometers and units in early archaeology and paleontology.

PMID- 17216898
TI  - Images in surgery: retroperitoneal Castleman's disease.

PMID- 17216899
TI  - The recovery and first analysis of an Early Holocene human skeleton from
      Kennewick, Washington.

PMID- 17216900
TI  - The Bluegrass fauna and changes in Middle Holocene hunter-gatherer foraging in
      the Southern Midwest.

PMID- 17216901
TI  - The British, the Indians, and smallpox: what actually happened at Fort Pitt in
      1763?

PMID- 17216902
TI  - The significance of in vitro studies.

PMID- 17216903
TI  - Fabricating sectional-collapsible complete dentures for an edentulous patient
      with microstomia induced by scleroderma.
AB  - Patients with microstomia who have to wear removable dental prostheses often face
      the difficulty of being unable to insert or remove the prosthesis because of the
      constricted opening of the oral cavity. This clinical report describes in detail
      the prosthodontic management of an edentulous patient with microstomia induced by
      scleroderma. Sectional-collapsible maxillary and sectional mandibular complete
      dentures were fabricated by means of sectional trays. With the use of palatal
      midline hinge and stud attachments, the sectional dentures were successfully and
      easily inserted and removed.

PMID- 17216904
TI  - Prevalence of oral mucosal lesions in a representative population.
AB  - OBJECTIVE: The aim of this study was to assess the prevalence and intraoral
      distribution of oral mucosal lesions in a representative adult population (Study
      of Health in Pomerania/Germany). METHOD AND MATERIALS: The study sample comprised
      6267 randomly selected subjects who were scheduled for examination from 1997 to
      2001 (population-based cross-sectional study; response rate: 69%; age range 20 to
      81 years). RESULTS: The prevalence of oral mucosal lesions was age dependent
      (5.56% in 20- to 29-year-olds to 19.55% in 70- to 81-year-olds) with an overall
      prevalence of 11.83%. The prevalence in men (12.20%) was slightly higher than in
      women (11.40%). Exophytic neoplasia was the most prevalent alteration (3.00%),
      followed by leukoplakia simplex (prevalence 2.85%). Premalignant lesions were
      found in 0.57% of the participants, with lichen ruber mucosae contributing the
      major part (0.48%). Exophytic neoplasia was most often situated in the buccal
      mucosa, the hard palate, or the mucosa of the lower lip. CONCLUSION: These data
      stress the importance of screening for oral mucosal lesions, especially because
      of a predicted increase in the number of elderly persons in industrialized
      countries.

PMID- 17216905
TI  - Connection between masticatory efficiency and pathomorphologic changes in gastric
      mucosa.
AB  - OBJECTIVE: The purpose of this investigation was to establish a connection
      between masticatory deficiency and pathomorphologic alterations of gastric mucosa
      in patients with dyspepsia. METHOD AND MATERIALS: In 40 dyspeptic, edentulous and
      partially dentate patients and in 40 dyspeptic control patients with good dental
      status, the Optosil masticatory function test was performed. Histopathologic
      changes of gastric mucosa and the severity of Helicobacter pylori infection were
      scored according to the updated Sydney Classification of Chronic Gastritis.
      RESULTS: The comminution of Optosil particles after increasing the number of
      chewing strokes was significantly impaired in edentulous and partially dentate
      patients, indicating masticatory deficiency in this group. This masticatory
      deficiency group was subdivided into groups with a lower (subgroup 1) and higher
      (subgroup 2) degree of masticatory deficiency according to median X50 in the
      Optosil test. The endoscopic appearance of gastric mucosa in masticatory
      deficiency patients and in the control group suggested chronic gastritis. Higher
      inflammatory and infection scores were noted in subgroup 2 than in the control
      group and subgroup 1, especially in the antral part of the stomach. The
      differences between the antral part and the body of the stomach were significant
      only in subgroup 2. CONCLUSIONS: Masticatory deficiency in patients with
      dyspepsia was connected with more severe chronic inflammatory changes and H.
      pylonri infection of gastric mucosa, especially in the antrum of the stomach.
      Higher values of inflammatory and infection scores in the subgroup with a higher
      degree of masticatory deficiency suggest its causal role in the promotion of
      gastritis and H. pylori infection.

PMID- 17216906
TI  - Bilaminar connective tissue graft as an alternative treatment of leukoplakia:
      case report.
AB  - Oral leukoplakia is a predominantly white lesion of the oral mucosa that cannot
      be clinicopathologically characterized as any other definable lesion. Any oral
      site may be affected by leukoplakia, the most common sites being buccal and
      alveolar mucosa, floor of the mouth, tongue, lips, and palate. To date there is
      no evidence of effective treatment of oral leukoplakia that may prevent
      recurrence. This case report describes a new surgical technique using a bilaminar
      connective tissue graft in the treatment of oral leukoplakia. During the regular
      periodontal recall visit, the clinical diagnosis of gingival leukoplakia at the
      maxillary left sextant was established in a 45-year-old patient. Histopathologic
      analysis suggested reactive hyperkeratosis. The patient agreed to a new surgical
      treatment of the lesion. Under local anesthesia a 20-mm-long bilaminar connective
      tissue graft was interposed between the affected tissue and the bone. Healing was
      followed by the disappearance of the white lesion within the borders of the
      underlying graft. Five years after therapy, the treated area remained intact,
      with no clinical sign of recurrence.

PMID- 17216907
TI  - Oral candidal carriage in children with and without dental caries.
AB  - OBJECTIVES: An epidemiologic study of 213 healthy children was carried out in 2
      age groups (4 to 6 and 7 to 12 years) to determine the potential relationships
      between oral Candida and dental status. METHOD AND MATERIALS: For each child
      included, a dental examination and mycologic investigation were conducted. The
      dental examination determined the index values for decayed and filled primary
      teeth (df-t) and decayed, missing, and filled permanent teeth (DMF-T). RESULTS:
      In the 4- to 6-year age group, the frequency of oral Candida in children with
      moderate and high df-t indexes was statistically higher than in caries-free
      children. By comparison, in the 7- to 12-year age group, high frequency of
      Candida was observed only in children with high dental indexes (both df-t and DMF
      T), but it was not significant. Generally, the intensity of candidal carriage in
      Candida-positive children was low, and it was not varied as a function of dental
      caries. Candida albicans was more frequently isolated, and it was the only
      species present in caries-free children. Other identified species were observed
      in children with different values of dental indexes. CONCLUSIONS: Mycologic
      examination may constitute a contributory role for epidemiologic studies of
      dental caries, especially in children under 7 years of age.

PMID- 17216908
TI  - Restoring function and esthetics in 2 patients with amelogenesis imperfecta: case
      report.
AB  - This case report describes the prosthodontic treatment for a 28-year-old man and
      a 16-year-old boy diagnosed with amelogenesis imperfecta. The aim of treatment
      was to reduce dental sensitivity and to restore esthetics and masticatory
      function. Because of the socioeconomic status of the patients, direct resin
      composite laminate veneers were used to improve the esthetics of their maxillary
      and mandibular anterior teeth. Clinical examination 12 months after treatment
      revealed no evidence of disorders associated with the restored teeth or their
      supporting structures. Definitive treatment outcomes in terms of function and
      esthetics satisfied the expectations of both the patient and the
      interdisciplinary team.

PMID- 17216909
TI  - Surface antibacterial properties of resin and resin-modified dental cements.
AB  - OBJECTIVE: Cements possessing antibacterial properties may reduce bacteria
      induced fixed partial denture complications. The purpose of this study was to
      evaluate the antibacterial properties of 4 dental cements using the direct
      contact test (DCT) and the agar diffusion test (ADT). METHOD AND MATERIALS: The
      ADT was performed using mitis salivarius agar plates. Each plate was evenly
      inoculated with freshly grown mutans streptococci. Two samples of each test
      material-RelyX ARC, Variolink II, GC FujiCEM, and Principle-were placed, and the
      inhibition halo obtained was measured after 48 hours. For the DCT, 8 samples were
      placed on the sidewalls of wells in a 96-well microtiter plate. After
      polymerization, freshly grown Streptococcus mutans cells (1 X 10(6)) were placed
      on the surface of each sample for 1 hour at 37 degrees C. Fresh medium was then
      added to each well, and bacterial growth was followed for 16 hours in a
      temperature-controlled spectrophotometer. Similarly prepared samples were aged in
      phosphate-buffered saline for 1 or 7 days and the DCT was repeated. Analysis of
      variance (ANOVA) and Tukey multiple comparisons were applied to the data.
      RESULTS: In the ADT, GC FujiCEM showed an inhibition zone of 2.0 +/- 0.3 mm, and
      Principle showed an inhibition zone of 1.2 +/- 0.2 mm. In the DCT, freshly
      polymerized samples of GC FujiCEM and Principle exhibited potent antibacterial
      properties, while samples of Variolink II and RelyX ARC showed moderate
      antibacterial properties. Principle showed some antibacterial properties even
      after 1 day (P < .001). CONCLUSION: None of the tested cements in this study
      possesses long-term antibacterial properties.

PMID- 17216910
TI  - Complicated late mandibular fracture following third molar removal.
AB  - Mandibular fractures are a rare complication after third molar removal. Symptoms
      show a wide variance. Treatment options range from prescription of a soft diet to
      surgical treatment by open reduction and internal fixation. This article
      describes a patient who presented a late mandibular fracture following third
      molar removal. The fracture was not detectable in radiographs at the time of
      fracture. Six weeks after the reported cracking noise, the patient presented a
      mandibular fracture with associated osteomyelitis. Treatment by open reduction
      and internal fixation and autologous iliac crest graft was performed via a
      submandibular approach. The delayed diagnosis of this pathologic fracture
      demonstrates the necessity of repeated radiologic controls to prevent
      osteomyelitis when a fracture is suspected.

PMID- 17216911
TI  - Influence of impression material and time on the 3-dimensional accuracy of
      implant impressions.
AB  - OBJECTIVE: To investigate, in vitro, the effect of time on the 3-dimensional
      accuracy of open-tray implant impression copings made of polyvinyl siloxane and
      polyether impression materials. METHOD AND MATERIALS: Reference models with 4
      internal connection implants were fabricated. Four sets of 71 direct impressions
      were made with square impression copings using an open-tray technique. One set of
      impressions was made with polyether material (material A) and each of 3 polyvinyl
      siloxane materials (materials B, C, and D). Three-dimensional changes in spatial
      orientation of the implant analogs were measured over 48 hours using an optical
      measurement device. Deviation values were summed over 4 points and averaged per
      impression. Global differences were tested with a nonparametric Kruskal-Wallis
      test followed by pairwise comparisons using the Mann-Whitney U test. RESULTS: The
      mean dimensional accuracy of implant impressions significantly differed over time
      (P < .001). Materials A and B were found to produce comparable results, For
      materials C and D there was a significant increase in deviations, with a maximum
      increase at 2 hours. Deviations for material C were comparable to materials A and
      B at 48 hours. Baseline values were not maintained by any material. CONCLUSIONS:
      Within the limits of this in vitro study, it can be concluded that time cannot be
      neglected as a factor affecting the accuracy of implant master casts.

PMID- 17216912
TI  - Prosthodontic treatment of hypohidrotic ectodermal dysplasia with complete
      anodontia: case report.
AB  - The hereditary condition known as ectodermal dysplasia is characterized by the
      absence or defect of 2 or more ectodermally derived structures. A case of a 6
      year-old child with hypohidrotic ectodermal dysplasia with complete anodontia is
      presented. Common dental, oral, and physical conditions were taken into
      consideration. Clinical management consisted of removable complete dentures to
      improve psychologic development and to promote better functioning of the
      stomatognathic system.

PMID- 17216913
TI  - [Obesity and endothelial dysfunction].
AB  - The endothelium plays a crucial role in modulating vascular function and
      structure. In healthy conditions, nitric oxide produced by endothelial cells
      exerts not only vasodilating properties, but also several other protective
      actions toward the vessel wall against the development of atherosclerosis and
      thrombosis. Traditional cardiovascular risk factors are characterized by
      endothelial dysfunction caused by an enhanced production of oxidative stress
      leading to destroy nitric oxide, thus reducing its availability. Abdominal
      obesity is associated with endothelial dysfunction, through direct mechanisms,
      such as insulin resistance and the association with risk factors (including
      diabetes mellitus, hypertension and dyslipidemia), and direct, by the production
      of adipokines and pro-inflammatory cytokines, which in turn induce oxidative
      stress leading to a reduced nitric oxide availability. A reduced endothelium
      dependent relaxation is a predictor of cardiovascular events in high-risk
      patients and represents a putative clinical parameter to stratify the
      cardiovascular risk and a useful marker for therapy efficacy. Weight loss and a
      modification of lifestyle ameliorate endothelial function in obese patients, an
      effect due not only to a better glycemic profile, but also secondary to reduced
      plasma levels of inflammatory markers and adipokines. At present, whether an
      improvement of endothelial dysfunction secondary to weight loss is significantly
      associated with a better cardiovascular prognosis is still unknown. (G Ital
      Cardiol 2006; 7 (11): 715-723)

PMID- 17216914
TI  - [Selection of patients undergoing cardiac resynchronization therapy: role of
      echocardiography].
AB  - Patients with heart failure, marked systolic dysfunction and dys-synchronous
      myocardial contraction are at increased risk for exacerbated pump failure and
      arrhythmias, and suffer higher mortality rates. In these patients, cardiac
      resynchronization therapy (CRT), achieved by a biventricular pacing, can lead to
      clinical improvement, reverse left ventricular remodeling and prolonged survival,
      although a substantial subset of non-responders has been reported. The
      electrocardiographic QRS width does not predict long-term CRT benefit, while
      direct measures of mechanical dyssynchrony obtained by various ultrasound
      techniques have been shown to have a better predictive value. However, currently
      there is no consensus on the optimal ultrasound technique to use for assessing
      mechanical dyssynchrony and select candidates for CRT. In this review, the
      clinical role of both conventional and new ultrasound techniques applied to the
      study of cardiac dyssynchrony will be discussed, focusing on patient selection
      for CRT.

PMID- 17216915
TI  - [Clinical use of a new class of anticoagulant drugs: the direct thrombin
      inhibitors].
AB  - The coagulation cascade, and particularly thrombin, plays a very important role
      in arterial and venous thrombosis. Thereby, it is clear that thrombin
      inactivation is an optimal strategy for thrombotic disease prevention and
      treatment. The direct thrombin inhibitors are a new class of anticoagulant drugs
      directly binding thrombin and blocking its interaction with fibrinogen. The group
      of direct thrombin inhibitors includes recombinant hirudin (lepirudin and
      desirudin), bivalirudin, melagatran and its oral precursor, ximelagatran,
      argotraban and dabigatran. These drugs have several advantages compared to other
      anticoagulant drugs, and the particular pharmacokinetic properties of some of
      them could be very important for future management of thromboembolic prophylaxis.
      The efficacy and safety of these new drugs are evaluated in several clinical
      trials; however today only few clinical indications are available for the
      majority of them.

PMID- 17216916
TI  - [Psychosocial factors as predictors of atherosclerosis and cardiovascular events:
      contribution from animal models].
AB  - Conventional risk factors (abnormal lipids, hypertension, etc.) are independent
      predictors of atherosclerosis and cardiovascular events; however, these factors
      are not specific since about half patients with acute myocardial infarction
      paradoxically result at low cardiovascular risk. Recent prospective studies
      provide convincing evidence that some psychosocial factors are independent
      predictors of atherosclerosis and cardiovascular events, as well. Psychosocial
      factors that promote atherosclerosis can be divided into two general categories:
      chronic stressors, including social isolation/low social support and work stress
      (subordination without job control) and emotional factors, including affective
      disorders such as depression, severe anxiety and hostility/anger. The emotional
      factors, such as the chronic stressors, activate the biological mechanisms of
      chronic stress: increased activity of the hypothalamic-pituitary-adrenal axis,
      sympathetic system and inflammation processes, which have atherogenic effects,
      and an increase in blood coagulation. In spite of the amount of published data,
      psychosocial factors receive little attention in the medical setting. About 30
      years ago, Kuller defined the criteria for a causal relation between a risk
      factor and atherosclerosis and cardiac events. The first of these criteria states
      that experimental research should demonstrate that any new factor would increase
      the extent of atherosclerosis or its complications in suitable animal models. We
      carried out a bibliographic research in order to investigate whether the results
      of the studies dealing with animal examination and experimentation support the
      psychosocial factors as predictors of atherosclerosis. Contributions related to
      some of the psychosocial factors such as social isolation, subordination and
      hostility/anger have been found. In these studies atherosclerotic extension has
      been evaluated at necroscopy; however, the incidence of cardiovascular events has
      not been investigated. As regards the biological mechanisms of chronic stress,
      the hypothalamic-pituitary-adrenal axis and the sympathetic system have been
      investigated. The studies have mainly been carried out on primates, and, to a
      less extent, on other mammals such as rabbit and wolf and on some species of
      birds. In the animals under social isolation, subordination or hostility/anger, a
      significantly more severe atherosclerosis was present, besides an increased
      activity of the hypothalamic-pituitary-adrenal axis and sympathetic system. In
      conclusion, the results offered by animal models seem to satisfy the first of
      Kuller's criteria, as for the three above-mentioned psychosocial factors.

PMID- 17216918
TI  - [Tricks, devices, expedients and stratagems in the management and interpretation
      of cardiological trials].

PMID- 17216917
TI  - [Comparative study of results of catheter ablation in ventricular tachycardia of
      different etiologies].
AB  - BACKGROUND: The aim of this study was to assess long-term results and adverse
      events in patients with ventricular tachycardia from different etiologies.
      METHODS: The recurrence rate of tachycardia, consequent further therapies (other
      catheter ablation procedures, drug therapy and implantable defibrillator) and
      clinical events have been assessed in 60 consecutive patients undergoing
      ventricular tachycardia catheter ablation between January 2000 and December 2004.
      RESULTS: During a median follow-up of 20 months (interquartile range 13-36
      months), tachycardia recurred in 27 patients (45%) after a median of 3 months
      (interquartile range 1-12 months). A second procedure was performed in 11
      patients; it was successful in 8 patients. Four patients underwent
      pharmacological therapy which was successful in all cases. Overall, after
      ablation (> or =1 procedures) and pharmacological therapy, tachycardia was cured
      in 75% of cases. All the 20 patients without structural heart disease were cured
      with ablation vs. 62% of patients with heart disease (p = 0.001). Patients with
      dilated cardiomyopathy reported worst results (33% success, p = 0.03).
      Recurrences were predicted by acute failure of procedure (p = 0.05), presence of
      heart disease (p = 0.006) and history of atrial arrhythmias (p = 0.02). On a
      multivariate analysis, only structural heart disease continued to be an
      independent predictor of ventricular tachycardia recurrence. CONCLUSIONS:
      Catheter ablation of ventricular tachycardia has a high percentage of recurrences
      in patients with heart disease, whereas is curative in subjects without
      structural heart disease.

PMID- 17216919
TI  - [Giancarlo Rastelli, a famous cardio-surgeon and an unknown saint].

PMID- 17216920
TI  - Relationship between indoor environmental physical factors and depression
      aspects.
AB  - The relationship between various physical indoor environmental factors and the
      level of the studied depression aspects had been investigated. The study has been
      tried to involve patients suffering from different levels of depression and
      treated at specialized mental hospitals. Significant negative correlation had
      established been the between efficient indoor physical environment such as
      available basic home facilities, ventilation and sunny environment, home
      satisfaction, neighborhood physical environment and work physical environment,
      and the increased levels of depression aspects namely, physiological, attitude,
      behavior, social, situational, self satisfaction and self insight of depression.
      Recommendations were advised to add improvement of indoor physical environment to
      the line of depression treatment and to evaluate the efficiency of improving the
      work physical environment and its outcome in improving the physical and mental
      health of the workers with expected increased productivity and efficiency of the
      exposed workers.

PMID- 17216921
TI  - Study of some biological markers of stress in nail industry.
AB  - The aim of this study was to investigate the different markers of stress in nail
      industry. Blood and urine biological samples were collected from 30 exposed
      workers and 30 age and sex matched control subjects from the administrative
      department of the same factory. The total antioxidant activity (Dmax) and lipid
      peroxidation was analyzed in blood. The level of catecholamines in the urine was
      also determined The median level of Dmaxwas significantly lower in the exposed
      workers (87.12) compared with that of the control (115.85) (p < 0.01). Also the
      level of lipid peroxidation was significantly lower in the exposed workers (44.5)
      compared with that of the control (74.0) (p < 0.01). The median level of urinary
      catecholamines was significantly higher in the exposed workers (295) compared
      with that of controls (37.5). Attention should be paid to the necessity of the
      application of the different biological markers of stress in different sectors of
      industry especially in nail industry.

PMID- 17216922
TI  - Immune response to hepatitis B vaccine in haemodialysis patients.
AB  - Widespread vaccination of haemodialysis patients had occurred during the year
      1999 as a result of the promulgation of the Ministry of Health & Population. To
      our knowledge, this might be the first study in Egypt concerning post-vaccination
      response in haemodialysis patients and possible risk factors influencing this
      response. Eighty-three haemodialysis patients vaccinated with 10 microg dose of
      recombinant hepatitis B Merck Sharp vaccine at 0, 1 and 6 months were enrolled in
      the study. Blood samples were withdrawn one month after the third dose and sera
      were tested for anti-HBc to exclude those who had previous HBV exposure and for
      quantitative determination of antibodies to hepatitis B surface antigen (anti
      HBs) using commercial enzyme immunoassay kits. Routine analysis for anti-HIV,
      anti-HCV and HBsAg every 3 months is done for all haemodialysis patients in the
      governmental sector. Only 65 patients negative for both anti-HBc and HBsAg were
      considered eligible for evaluating the immunogenicity of the vaccine.
      Seroconversion rate (anti-HBs>10 mlU/ml) was detected in 64.6% and adequate
      response (anti-HBs>100 mlU/ml) was achieved in 38% only. Non-responders were
      35.4% reflecting the profound immune suppression in haemodialysis patients.
      Seroconversion rate was 84.2% in patients below 40 years of age and dropped to
      33.3% in those 60 years or above. Seroconversion was significantly higher in
      females than males (76.5% vs. 51.6%). HCV infection was strikingly high among
      dialyzed patients (78.5%). Seroconversion rate was 58.8% in HCV-infected and
      85.7% in non HCV-infected haemodialysis patients. Neither the duration of
      haemodialysis nor the frequency of blood transfusions had any significant
      association with seroconversion rate.

PMID- 17216923
TI  - Diagnosis of giardiasis using an enzyme-linked immunosorbent assay (ELISA) on
      formalin preserved stools.
AB  - From a total of 162 children, three stool samples were collected from each child
      over a period of one week and preserved in formalin. Giardia lamblia was
      diagnosed by direct microscopy of formol-ether concentrates for each of the three
      samples. The first sample was also subjected to an ELISA test for detection of
      Giardia Iambia stool antigen in formalin preserved stool specimens. Microscopic
      examination revealed that 45 children were infected whereas ELISA detected 41
      cases giving a sensitivity of 91.1% and a specificity of 99.1%. Predictive value
      of a positive test was 97.6% and that of a negative test was 96.7%. A significant
      correlation was present between mean optical density readings of ELISA and number
      of cysts present. No crossreactivity was observed ELISA is a simple, sensitive
      and specific test that can be applied in epidemiological studies for detection of
      Giardia lamblia coproantigen in formalin preserved stool specimens.

PMID- 17216924
TI  - Effect of teaching unit about sexuality and sexual health on nursing students
      knowledge at Zagazig University.
AB  - The aim of the study was to assess the effect of teaching unit about sexuality
      and sexual health on Zagazig University nursing students' knowledge. The sample
      included all student nurses (0=200) in the obstetric and Gynaecology nursing
      course during the 1st semester of the 3rd academic year (1999). Two tools were
      used for data collection; the first tool was a questionnaire to assess the
      student's knowledge about sexuality and sexual health e.g. Anatomy and physiology
      of female and male reproductive systems, the tool was given to the students
      twice; before and after conducting the teaching unit. The results concluded that
      the majority of the students lacked knowledge in all study parameters before the
      teaching unit. The students' knowledge showed a significant improvement after the
      teaching unit. It can be recommended that sex education and sexual health should
      be included in the university nursing curriculum.

PMID- 17216925
TI  - Effect of the carbamate "aldicarb" on acetyl cholinesterase extracted from whole
      and different parts of rat brain (in vitro and in vivo studies).
AB  - Aldicarb, a synthetic carbamate compound used as an insecticide and herbicide, is
      also employed as a pharmacological cholinergic agent in therapeutic forms.
      Inhibition of the enzyme AChE, which results in accumulation of ACh, is the basis
      for its use as an insecticide and it resulted in toxicity in a variety of animals
      including man. In this work, experiments were carried out in vitro and in vivo to
      study the effects of aldicarb on the activity of ChE enzyme extracted from whole
      and five different parts of rat brain, namely: basal ganglia, frontal cortex,
      medulla oblongata, pons and cerebellum. Kinetic measurements of Michaelis
      constants (Km), enzyme inhibitor dissociation constants (Ki) as well as the rate
      of carbamylation (k2c) and binding constants (Kl) for the inhibition of the
      enzyme obtained from the different parts were done. The carbamylation rate
      (degree of inhibition of AChE by carbamate) and binding constant for inhibition
      of whole and different parts of brain in vitro, indicated that the carbamylation
      rate constants of pons, medulla oblongata and cerebellum were higher than those
      of other parts. Inhibition of AChE in the different parts of the brain in vitro
      by aldicarb was of the competitive type, with different enzyme inhibitor
      dissociation constants (Ki). In vivo studies showed that the inhibition was
      marked in the enzyme obtained from pons, medulla oblongata and cerebellum; the
      parts responsible for vital centers and balance which coinsize with the in vitro
      results.

PMID- 17216926
TI  - Magnesium deficiency and other risk factors for diabetic retinopathy.
AB  - A case control study was carried out to detect the relation between magnesium
      deficiency and diabetic retinopathy and to study other risk factors for diabetic
      retinopathy. The study involved 30 cases with diabetic retinopathy, 30 diabetics
      and 30 non-diabetics with normal retina as controls. Serum magnesium was
      significantly lower in the diabetic control group than both other groups.
      Significant association between diabetic retinopathy and hypertension, poor
      control of blood sugar, irregularity in drug treatment, lack of routine fundus
      examination, high gravidity and low socioeconomic status were found. Multiple
      regression analysis was used to adjust for all variables mentioned. Magnesium
      deficiency was found to be statistically significantly associated with diabetic
      retinopathy after considering the effects of other variables.

PMID- 17216927
TI  - Environmental safety conditions for mobile base stations in Alexandria.
AB  - The use of wireless communications devices e.g. cellular phones is increasing
      rapidly all over the world and in Egypt as well. This translates into a
      potentially significant public health problem: how far is the risk associated
      with these devices? Another risk is expected from the cellular towers or base
      stations, which transmit and receive these electromagnetic waves. Usually, these
      base stations should be constructed over residential buildings to cover all
      areas. Considering the increased public awareness about electromagnetic fields
      (EMF) exposure associated with these towers, this work aimed at investigation and
      evaluation of authorized environmental safety conditions for some mobile base
      stations in different districts of Alexandria city. The different mobile base
      stations were investigated for 12 standard safety specifications of the
      buildings' roofs on which mobile base stations are constructed. Although some of
      the standard specifications in the examined base stations were in compliance with
      standard specifications, some items were not in a safe condition. Only base
      stations F & G had complete safe conditions for all investigated items because of
      being erected on lighting towers of a sports stadium. On the other hand, base
      stations C, D, E, I, J, K, L1 & L2 needed a raise in the height of the antennas
      over buildings' roofs of 1-4.5 m. However, base stations C, D, H, K, L1 & L2 may
      pose a risk to near living population and consequently the towers have to be
      moved away. The violating distances are 3, 5.5, 3, 4.5, 4, 3 meters,
      respectively, while the environmental standard is 6 m. Therefore, the towers
      should be moved away from these populated areas Nevertheless, guided directions
      should be constructed in all base stations to warn close living population.
      Safety regulations as well as frequent inspection need to be applied, on both
      Egyptian mobile phone companies, to ensure the application of all standard
      specifications. A significant research effort is needed to assess the risk to
      human health of wireless communication devices.

PMID- 17216928
TI  - Seroprevalence of certain hepatitis viruses among Egyptian workers infected with
      schistosomiasis.
AB  - This investigation was carried out on 233 workers from four wastewater treatment
      plants (WWTP). in order to detect the prevalence of hepatitis E. C and B viruses
      among those workers and the relationship of the prevalent viruses with
      schistosomal infection. The result showed that the highest single infection was
      with HEV and Schistosoma (50.6% and 50.4%, respectively) in the four (WWTP). For
      schistosomiasis infected workers, the coinfection with HEV and HCV were the
      highest single viral infection (63.9% and 40.2%, respectively). The combined
      infection with HEV+HCV in schistosomiasis workers was 35.3%, while for HCV-HBV
      was the lowest combined infection (9.0%). Therefore, it is very important to
      follow up these workers with the highest infection rate, as they can be potential
      risk group for the spread of viruses. Out of the four (WWTP), the workers at
      Helwan exhibited the highest infection rate.

PMID- 17216929
TI  - Primary colonic lymphoma presenting as a fever of unknown origin.

PMID- 17216930
TI  - Prevalence and factors associated with genital prolapse: a hospital-based study
      in Alexandria (Part I).
AB  - Most hospital-based studies on genital prolapse focus on the contribution of
      prolapse to the overall hospital incidence rate of hysterectomy. The present
      study targeted the outpatient clinic of a teaching and reference hospital (The
      Maternity University Hospital in Alexandria) to determine the prevalence and
      possible factors associated with genital prolapse among the attendants of the
      gynecological outpatient clinic. Through a cross sectional approach, a systematic
      random sample of 400 women (being non-pregnant, age 25 years and over), was
      selected from the outpatient clinic over a period of 6 months. They were
      subjected to: 1) a structured interview using a questionnaire, 2) clinical
      examination, and 3) measurement of body mass index (BMI). Pelvic examination
      revealed a high prevalence rate, moderate and large degrees were present in 40%
      of them. Cysto-rectocele was the commonest type (65.5% of the whole sample),
      followed by utero-vaginal prolapse (3.5%). The most commonly reported complaints
      (89.9%) were not related to genital prolapse. Symptoms specific to prolapse were
      reported on inquiry by a small proportion of cases (25.8%). Comparing women's
      report and diagnoses indicated a low sensitivity (33%) and very high specificity
      (100%). Stress incontinence and multiple sexual consequences were the most
      frequently reported complications (60.1% and 66.7% respectively). Stepwise
      logistic regression analysis revealed that five variables only were significant
      predictors of prolapse: parity 3+ (p = .0001, CI = 1.67-5.25), unskilled birth
      attendant (p = .0006, CI = 1.2-3.2), prolonged labor (p = .007, CI = 1.7-7.6),
      early resumption of routine activities during puerperium (p = 002, CI = 1.7-11.3)
      and history of obvious weight loss (p = .0026, CI = 1.19-17.2). The presence of
      many silent cases of prolapse among outpatients in spite of having moderate and
      severe degrees indicates that health education on different aspects of
      reproduction is highly required to encourage women to know and report their
      sufferings. Improving the skills of birth attendants, focussing on domiciliary
      obstetrics is also emphasized.

PMID- 17216931
TI  - Perception of genital prolapse: a hospital-based study in Alexandria (Part II).
AB  - Genital prolapse is a common health problem, understanding women's perceptions
      and beliefs may illuminate our understanding of their health seeking behavior
      which form a first step in any effort to improve their health. The present study
      was designed to investigate the perception of genital prolapse among women
      attending the outpatient clinic in El-Shatby Maternity University Hospital in
      Alexandria. Data was collected from a sample of 291 women who had any form of
      genital prolapse. Women's knowledge about risk factors for genital prolapse,
      women's beliefs related to genital prolapse as well as their beliefs about
      assistance at delivery (beliefs were assessed through the Health Belief Model)
      were measured for women who knew that they were suffering of genital prolapse (n
      = 40). The results revealed that more than two thirds of cases (70.4%) had poor
      (36.4%) or fair knowledge (34%) and only 29.6% had satisfactory knowledge. The
      majority of women having positive perception to diagnosis and symptoms for
      genital prolapse had high perception of "susceptibility" to and "severity" of
      complications of genital prolapse (97.5% and 85% respectively). More than two
      thirds (67.5%) had high scores of "perceived benefits" of treatment and medical
      advice, while nearly one third (32.5%) scored moderate. The majority of women
      (82.5%) had either moderate scores (55%) or high scores (27.5%) of perceived
      barriers to compliance to medical instructions or recommended surgery. About two
      thirds of cases (65.6%) sought medical care later than one year of perception of
      symptoms. Women's knowledge and degree of genital prolapse were directly related
      to women's report of symptoms characteristic of prolapse, while the level of
      education was inversely related. Health education for women on different aspects
      of reproduction using appropriate materials is highly recommended.

PMID- 17216932
TI  - Pre-eclampsia: epidemiology and outcome of 995 cases.
AB  - OBJECTIVE: To study the epidemiology and pregnancy outcome of pre-eclampsia at
      Ain Shams University Hospital for Obstetrics and Gynecology. STUDY DESIGN: A case
      control study involved 995 cases of pre-eclampsia, 227 cases with chronic
      hypertension and 1375 cases with normal pregnancy delivered during the year 2000
      at Ain Shams University Maternity Hospital. All these cases were critically
      analyzed regarding to some risk factors as age, parity, blood group, diabetes
      mellitus, Rhesus factor and multiple pregnancy. The outcomes of all these 3
      groups were compared regarding to maternal and fetal morbidity and mortality.
      RESULTS: Pre-eclampsia was more common in elder age, blood group B, in Rhesus
      negative, during summer, multiple pregnancy and in patients with diabetes
      mellitus. The difference was statistically significant regarding all these risk
      factors (p < 0.01) when compared with cases of chronic hypertension and patients
      with normal pregnancies. CONCLUSIONS: In this work pre-eclampsia was found to be
      an important cause for maternal and fetal mortality. Also it was found to be an
      important cause for premature deliveries.

PMID- 17216933
TI  - Development of weight gain charts for healthy Egyptian pregnant women.
AB  - A prospective study was conducted to develop weight gain charts for healthy
      Egyptian pregnant women and to determine the relationship between different
      anthropometric indicators and favorable birth weight. A total of 830 pregnant
      women were enrolled in the study. The mean total weight gain was 9.3 kg. The
      velocity growth chart that were developed for weight gain showed that the
      increment of weight was about one kg up to the 4th gestational month, then, a
      steady increase of 0.37 kg per week till the end of pregnancy. The mean total
      gain in mid upper arm circumference (MUAC) was 0.8 cm and in triceps skin fold
      was 1.9 mm. There was a highly positive correlation between all anthropometric
      indicators studied and the birth weight. However only total weight gain and
      weight of the mother at first trimester showed significant relation with birth
      weight after using multi regression analysis. It is recommended to use the
      developed weight gain charts for monitoring the nutritional status of pregnant
      women and the MUAC and triceps skin folds are to be used for screening women at
      risk for malnutrition.

PMID- 17216934
TI  - Prevalence and possible risk factors of Helicobacter pylori infection among
      children attending Damanhour Teaching Hospital.
AB  - Helicobacter pylori (H. pylori) is a major cause of gastrointestinal disease in
      children. The factors influencing the acquisition and prevalence of H. pylori
      infection remain incompletely understood. In the present study, the prevalence
      and possible risk factors of H. pylori infection were studied among children aged
      1.5-16 years who were attending the pediatric outpatient clinic of Damanhour
      Teaching Hospital. Blood samples were drawn and IgG seroprevalence of H. pylori
      among the studied children was determined using ELISA kits. A specially designed
      questionnaire inquired about personal, socioeconomic, household characteristics,
      feeding history during infancy and the child's health data was completed for
      every child. Results revealed that the overall seroprevalence of H. pylori
      infection was 50.5 %. The prevalence was widely age dependent: it was 60.6% among
      those age > or = 5 years and only 25.9% among those < 5 years (OR = 4.4; 95% CI =
      1.6-11.9). Increased crowding in bed was also an associated factor; the
      prevalence among children where > or = 3 share a bed was 59.7% compared to only
      26.9% among those where < 3 persons share a bed (OR = 4.1; 95% CI = 1.5-10.9).
      The prevalence among children who were breast fed for < 1 year was 64.7% compared
      to only 42.4% among those who were fed for > or =1 year (OR = 2.5; 95% CI = 1.1
      5.9). After controlling for possible confounding in a Stepwise Multiple Logistic
      Regression model, independent predictors for H. pylori infection were: increasing
      age (> or = 5 years), overcrowding in bed (> or = 3/ bed) and shorter duration of
      breast-feeding (< 1 year) during infancy. It could be concluded that, H. pylori
      was highly prevalent among the sampled children and the possible risk factors are
      related to the community. So, there is a need to early diagnose, treat and
      eradicate infection during childhood to prevent its complications during
      adulthood.

PMID- 17216935
TI  - Validation of a patient satisfaction scale for primary care settings.
AB  - The objective of this study was to develop and validate an instrument pertinent
      for the Egyptian culture and situation suitable for use by health centres'
      administrators as a complementary tool for assessing the quality of outcome of
      care rendered. The study describes an attempt to develop and validate an
      instrument of patient satisfaction with primary health settings in Alexandria. A
      systematic randomized sample (227) of patients attending the outpatient clinics
      at 4 primary health centres in Alexandria were included in the study. The
      instrument included a section for respondents' characteristics, and the other
      section was a 5-point Likert-type scale ranging from highly satisfied (5) to
      highly dissatisfied (1) was developed by adapting items from other measures of
      patient satisfaction in the literature. The internal consistency of the
      instrument was determined, and the Cronbach's alpha coefficient for all scales
      was 0.80. Using the principal components factor analysis factor loadings for the
      scale items were high on seven factors. The factors were named technical care,
      accessibility, structure, humaneness, respect, in return for cost, and the
      waiting time. The study supports that the instrument is a reliable and valid
      measure for patient satisfaction suitable for Egyptian primary health settings.

PMID- 17216936
TI  - The potential role of Rattus rattus in enzootic cycle of Rift Valley Fever in
      Egypt. 1-Detection of RVF antibodies in R. rattus blood samples by both enzyme
      linked immuno sorbent assay (ELISA) and immuno-diffusion technique (ID).
AB  - Three hundreds of Rattus rattus (R. rattus) were trapped from 3 different
      governorates of Egypt (one hundred each), blood samples were withdrawal and
      subjected for detection of anti-RVF antibodies by both ELISA and ID techniques.
      The prevalence rate of antibodies by ELISA were 88 (29.33%) positive out of 300
      tested blood samples, the highest rate was in Behira governorate 36 (36%) and the
      lowest one was in Alexandria governorate 22 (22%) while it was 30 (30%) in Minia
      governorate. But when ID technique was applied, it gave only 18 (6%) positive
      samples out of 300 tested blood samples with the highest rate in Behira and Minia
      governorates (8%) and it was only (2%) in Alexandria governorate. Our study
      suggests that these R. rattus make possible candidate as intermediate host in the
      maintenance cycle of RVF in Egypt.

PMID- 17216937
TI  - Health locus of control beliefs among school children.
AB  - The purpose of the present study is to measure Children Health Locus of control
      (CHLC) beliefs among school children using the scale developed by Abdel-Gawwad et
      al. (1999) to test the differences of the beliefs by children's some
      sociodemographic characteristics and Body Mass Index (BMI). A cross sectional
      study design was applied using a stratified random sample of 1500 pupils from the
      final two grades of primary and all grades of the preparatory schools. The scale
      consisted of 25 statements with a 4-point Likert format. Body mass index was also
      calculated. From data analysis 15% of the pupils were obese. The mean score of
      internality increase with increasing age also powerful others' mean score
      increase with increasing age till the age of 11 - < 12 years and decrease again
      till the age14 - < 15 years. Chance's mean score decreases with increasing age
      till the age 14 - < 15 years. Self blame and fate subscales showed irregular
      decrease with increasing age. Girls had significantly higher mean score of fate
      subscale than boys (F = 10.67, p < 0.01). Boys had significantly higher mean
      score of total CHLC scale than girls (12.68, p < 0.01). Obese pupils had
      significantly higher mean scores of internality and total CHLC scale than non
      obese pupils (t = 2.58, 2.02, p < 0.05, respectively). Obese pupils had
      significantly lower mean scores of powerful others, chance and self blame (t =
      2.09, 16.51, 2.00, p < 0.05, 0.01, 0.05, respectively). Total CHLC mean scores
      increased with increasing mother's education (F = 8.99, p < 0.01). Chance mean
      score decreased with increasing mother's education (F = 11.43, p < 0.01). Total
      CHLC mean scores increased with increasing father's education (F = 7.6, p <
      0.01). Powerful others mean score decreased with increasing father's education (F
      = 4.42, p < 0.01). Pupils from private schools had higher mean scores of chance
      and total CHLC (t = 7.0, 7.26, p < 0.01, respectively). They also had lower
      powerful others and fate mean scores (t = 4.19, 3.17, p < 0.01, respectively).
      Measuring CHLC beliefs to plan health education programs according CHLC scores is
      highly recommended.

PMID- 17216938
TI  - Prevalence of infertility in rural areas of Kafr El-Sheikh-Egypt: a community
      based study.
AB  - The current study was carried out in Desok district-Kafr El Sheikh province, to
      measure the prevalence of primary and secondary infertility among rural women and
      to study some risk factors as well. The study included 1125 married women between
      15-49 years. The results of the study showed that; 7.9% reported secondary
      infertility 2.5% experienced primary infertility, the prevalence of primary
      infertility is higher among women under 30 years than older ages, and secondary
      infertility increases with advance in age. Both types of infertility were higher
      among women married under the age of 16 or above 30 years. There was an
      insignificant difference between fertile group and infertile groups regarding age
      at menarche. Irregular menses was significantly higher among infertile groups
      compared to fertile group. Secondary infertility group had significant higher
      abortion and difficult labor than fertile group. There was an insignificant
      difference between the study groups regarding illiteracy rate. Chronic illnesses
      of women as well as husbands were significantly more reported among women with
      secondary infertility. In conclusion, the overall prevalence of infertility is
      10.4 %.

PMID- 17216939
TI  - Waterborne viruses associated with repeated abortion.
AB  - In this study we tried to find the role of some waterborne viruses in repeated
      abortion of women. The study includes maternal blood serum and fetal tissue. The
      serum of full-term delivered women was taken as a control. All collected samples
      were inoculated on BGM and Hep2G cells to detect entero and Hepatitis E viruses.
      Enzyme-linked immunosorbent assay was also carried out for IgM and IgG antibodies
      against HEV in all serum samples. HEV-Ag was determined by dot-ELISA, which used
      also for enterovirus typing. Reverse transcriptase polymerase chain reaction was
      used for detection of entero and HE virus RNAs in the collected serum samples. To
      follow up the source of virus transmission, the wastewater treatment plant which
      serves the area of samples population was studied at the intake and the final
      effluent for the presence of hepatitis E virus and enteroviruses with special
      reference to coxsackieviruses. Wastewater samples were collected for 1 year and
      for enterovirus concentration the adsorption-elution on nitrocellulose membrane
      was used and for HEV, two methods of virus concentration were used, urea arginine
      phosphate buffer (U-APB) and PEG8000. The results of HEV investigation of aborted
      women sera was 22% for IgG, 3% for IgM, 20% HEV-Ag, and 16% of HEV-RNA by RT-PCR.
      For fetal tissue, HEV-Ag was detected in 5% of the collected samples. The
      detected enteroviruses were coxsackieviruses types 2, 3,4 and 5 in all serum
      samples and wastewater samples. The results showed also, that virus concentration
      by U-APB is much better than PEG-8000 but not highly efficient.

PMID- 17216940
TI  - Experimental infection of rabbits with Fasciola gigantica and treatment with
      triclabendazole (TCBZ) or BT6: parasitological, haematological and immunological
      findings.
AB  - The responses of rabbits experimentally infected orally with 25 Fasciola
      gigantica metacercariae each, to treatment with triclabendazole (TCBZ) in a
      single oral dose of 10 mg/Kg body weight or with the newly synthesized drug (BT6)
      in repeated oral doses of 500 mg/Kg for 3 consecutive days, were monitored by
      faecal egg and fluke counts and the enzyme-linked immunosorbent assay (ELISA),
      both treatments at 4-, 8- and 12- weeks of infection. In all infected rabbits,
      eggs appeared in the faeces between 10 and 16 weeks post-infection (P1) and Were
      egg-negative in the TCBZ-treated animals. Compared with the infected untreated
      control (group B), the reduction in the fluke burdens were 93.75,100 and 100% in
      TCBZ-treated rabbits (groups C, D and E), respectively and 33.33, 27.08 and
      27.08% in the BT6 treated groups F, G and H, respectively. Total red blood
      corpuscle (RBCs) counts, haemoglobin (Hb) concentration and packed-cell volume
      (PCV) values in rabbits (group B) indicated the presence of moderate anaemia from
      the start of infection with a significant decrease from 10-12 weeks onwards. RBCs
      count, Hb and PCV values from groups C, D and E were significantly higher (p <
      0.001) than in those from group B on week 10, 8 and 10 PI, respectively. The
      increasing was continued till week 16 PI. By two weeks PI there was significant
      eosinophilia in infected rabbits, maintained at 4 and 6 weeks PI then dropped up
      to 8 weeks but still statistically higher than the control values. The ELISA
      detected antibodies against F. gigantica as early as week 2 PI, rising to high
      levels 6, 10 and 12 weeks later in groups C, D and E, respectively, whilst peaked
      at 10 weeks in BT6 treated animals, then tended to drop but remained positive
      through 16 weeks. We conclude TCBZ is a potent fasciolicidic drug. Eosinophilia
      and anaemia might be indicators for fascioliasis. The ELISA with adult fluke
      excretory - secretory (ES) antigens could be a feasible method for the diagnosis
      of experimental fascioliasis in rabbits and post-treatment monitoring.

PMID- 17216941
TI  - Infection by certain arboviruses among workers potentially at risk of infection.
AB  - Egyptian workers at sewage treatment plants (STPs) work and live in areas, which
      are highly infested with arthropods. Most of these diseases cause, febrile,
      influenza like illness, headache, backache, abdominal pain, and fatigue. To
      determine arboviral etiology in those workers, 264 serum samples were obtained
      from the workers in four STPs during January and October 1999. Enzyme linked
      immunosorbent assay (ELISA) was performed for immunoglobulins (IgG and IgM), for
      the detection of West Nile (WN), Sindbis (SIN), Rift Valley fever (RVF), Sandfly
      Naples (SFN) and Sandfly Sicilian (SFS) viruses. The results showed that (WN) has
      the highest prevalence (143/264, 54.14%), followed by (SFN) (58/264, 21.97%) then
      (RVF) (23/264, 7.95%), while, only one recent infection for each of RVF, SFS and
      SFN (1/264, 0.38%) and 3 persons for SIN viruses. Out of the four STPs Helwan
      workers' exhibited the highest infection rate for most of the studied arboviruses
      WN, SFN, SIN and SFS.

PMID- 17216942
TI  - Quality assessment of primary health care services provided for diabetes mellitus
      control in Alexandria.
AB  - Diabetes is a growing health problem worldwide. It is recognized as a particular
      threat to public health of the third world communities, particularly those living
      in rapidly developing countries. Therefore, the present study was conducted
      aiming at: assessment of the quality of primary health care (PHC) services
      provided for the control of diabetes mellitus (DM) in Alexandria; and
      opportunistic screening of high risk individuals attending PHC facilities for DM.
      Accordingly, the availability of human and nonhuman resources for DM control in
      two rural and two urban PHC centers in Alexandria (one of them was serving a
      desert area) was assessed by a pre-designed checklist 920 adult PHC attendants
      were screened for risk factors of DM. Individuals having more than one of the
      following risk factors: age above 50 years, overweight (body mass index > or =27
      kg/m2), family history of DM in first degree relatives, history of hypertension,
      hypertension (systolic blood pressure > or =140 mm Hg and /or diastolic blood
      pressure > or =90 mm Hg), history of hyperlipidemia and history of gestational
      diabetes or birth of a large sized baby in females- were subjected to random
      capillary blood glucose (RCBG) testing. Cases were considered likely diabetic if
      RCBG was >200 mg/dl The performance of all PHC physicians examining and managing
      560 diabetic patients was observed over a period of two months. One fourth of the
      diabetic cases were checked for the level of glycaemic control by fasting
      capillary blood glucose testing. The results revealed that 61.7% of the studied
      PHC attendants were at risk of developing DM and 14% were likely diabetic, with
      an urban: desert ratio of 2:1 The following factors were found to be
      independently associated with an increasing risk of DM occurrence among males:
      overweight (about 14 folds), family history of DM (9 folds), age above 50 years
      and history of hypertension (4 folds each). Whereas, among females the following
      risk factors were found: family history of DM (8 folds), history of gestational
      diabetes (6 folds) and overweight (4 folds). The majority of diabetic patients
      were poorly examined, investigated and managed; and an optimal level of glycaemic
      control was achieved in only 12.9% of the cases, as the PHC physicians didn't
      follow a model treatment plan for DM and due to unavailability of some equipment,
      laboratory facilities and essential drugs.

PMID- 17216943
TI  - Assessment and upgrading of Alexandria University nursing students' knowledge and
      attitudes about genetic counseling.
AB  - The aim of this study was to study the effect of a teaching unit on upgrading
      university-nursing students' knowledge and attitudes about genetic counseling.
      The study used pre- test, posttest with no control group design. All nursing
      students (100) who accepted to participate in the study and enrolled in the
      Maternity and Gynecological-nursing course, during the second semester of the
      third academic year 1999-2000, at the Faculty of Nursing, Alexandria University,
      were involved in the study. A self-administered questionnaire sheet was used to
      assess nursing students' knowledge about genetic counseling, while a 3-point
      Likert-like scale was used to assess their attitudes towards it. The content of
      six-hours' teaching unit -about genetic counseling was taught to students by the
      researchers based on their needs. The study revealed a general lack of knowledge
      among nursing students regarding basic information about genetic counseling,
      where poor total score of knowledge was obtained by all of them in the pre-test.
      In addition, the pre-test revealed that negative attitude was found in about half
      of the nursing students. The teaching unit had an obvious effect on the nursing
      students' knowledge and attitudes regarding genetic counseling, as the total
      score of their knowledge and attitudes had improved after implementation of the
      teaching unit. Moreover, there was a significant relationship between nursing
      students' knowledge and attitudes towards genetic counseling before and after
      implementation of the teaching unit. Therefore, a negative attitude was found
      with poor total score of knowledge in the pre-test and positive attitude was
      found with good total score of knowledge in the post-test. So, there is a need to
      improve knowledge and change attitude of nursing students about genetic
      counseling. As well as genetic counseling should be included in the university
      nursing curriculum and should be reviewed periodically to accommodate the
      relevant fast change in the science and technology of genetics. Moreover, nursing
      students must be informed about the different community resources, which offer
      the genetic counseling services.

PMID- 17216944
TI  - Effect of technical traning program on intern physicians' and nurses' knowledge
      and attitudes regarding emergency contraceptives.
AB  - In spite of the effectiveness of modern contraceptives, unwanted pregnancies
      occur in large number throughout the world and many seek termination so emergency
      contraceptive methods can be used by women in the first few days, following
      unprotected intercourse to prevent unwanted pregnancy, induced abortion, and its
      consequences for women and couples. So this study was conducted to determine the
      effect of technical training program on upgrading a newly graduate physician and
      nurses knowledge and attitude regarding emergency contraceptives. The study
      included 50 intern physicians and 50 intern nurses who are working at El-Shatby
      maternity university hospital during 1st of march 2001. The study used pre and
      post test with no control group design. An interview questionnaire sheet was used
      to assess intern physician and nurses, knowledge about emergency contraceptives
      while 3 point Likert scale was used to assess the attitude of both groups
      (physician and nurses) were divided into two sub group. A four hours technical
      training program were implemented for each group separately on two successive
      days (2 hours/day). Before implementing the technical training program the study
      depicted a general lack of knowledge among all physician and nurses regarding
      emergency contraceptives. Methods added to that the majority of intern physician
      and nurses 70%, 84% respectively had negative attitude toward emergency
      contraceptives however, the technical training program had an obvious effect on
      intern physicians and nurses. Knowledge regarding emergency ,contraceptives.
      Although improving in the study subjects, Knowledge had a positive impact of
      their attitude toward emergency contraceptives.

PMID- 17216945
TI  - The role of primary health care in patient education for diabetes control.
AB  - The major components of diabetes management are dietary therapy, exercise and
      drug treatment. Therefore, education of people with diabetes is the cornerstone
      of management. The aim of the present work was to study the role of primary
      health care (PHC) in patient education for diabetes control in Alexandria.
      Accordingly, the knowledge and perception concerning diabetes and its management
      of all 88 PHC physicians and 104 nurses working in the two rural health centers
      and two randomly chosen urban health centers of Alexandria governorate were
      assessed by pre-designed self-administered questionnaire. All diabetic patients
      over 20 years of age attending the study health facilities over a period of two
      months were assessed for their knowledge and attitude concerning diabetes and
      self-management and asked about their degree of satisfaction with the provided
      PHC services by a pre-designed interview questionnaire. They amounted to 560
      diabetic patients. The results revealed that the PHC physicians had sufficient
      knowledge about causes and complications of the disease, but insufficient
      knowledge about diagnosis and management, as only 10.2% & 4.5% of the physicians
      recognized the importance of regular exercise and patient education for diabetes
      management. Some misconceptions and false beliefs were observed among PHC nurses,
      as many of them considered diabetes a contagious disease or primarily caused by
      stress; that liver failure, hearing impairment and splenomegaly are among the
      complications of diabetes and that young age and immunodeficiency disorders are
      among the risk factors for developing diabetes. Moreover, most of them believed
      that the amount of carbohydrates given to diabetic patients should be reduced or
      even completely restricted; that vitamins are essential for all diabetic patients
      and that hot-water bottles are good for providing warmth to the diabetic feet.
      They also disagreed on the use of artificial sweeteners as sugar substitutes.
      Most of the diabetic patients had poor knowledge about diabetes and its
      management (85.7%) and a negative attitude towards self-management (61.6%) and
      only 23.6% of them were satisfied with the services provided by the PHC
      facilities for diabetes control. They were mainly dissatisfied with the role of
      PHC physicians in patient education. Some misconceptions and false beliefs were
      also recognized among diabetic patients. Many of them considered diabetes a
      contagious disease or primarily caused by stress. They didn't know the importance
      of regular exercise in diabetes control. They also believed in the efficacy of
      herbal therapy in diabetes control; that vitamins are essential for all people
      with diabetes; that water intake should be decreased when passing large amounts
      of urine, that anti-diabetic drugs should be stopped during associated illnesses
      and that patients on insulin treatment can't be shifted to oral drugs. Moreover,
      they believed that the amount of carbohydrates in diet should be reduced or even
      restricted and that the amount of proteins should not be reduced. They also
      refused the use of artificial sweeteners as sugar substitutes. Thus, it may be
      concluded that there is a serious gap in the provision of basic educational
      services to the majority of diabetic patients attending PHC facilities in
      Alexandria.

PMID- 17216946
TI  - The association of Helicobacter pylori infection with the development of
      gastroesophageal reflux disease (GERD).
AB  - A large number of studies were performed that support the association of
      Helicobacter pylori infection and the development of (GERD), although to prove
      that this association is a causation is still a matter of dispute. The objectives
      of this study was to prove this causal association in order to be able to plan a
      program for intervention. The work was conducted on 30 patients suffering from
      symptoms suggestive of gastro-esophogeal reflux disease diagnosed by upper
      endoscopic examination and 20 matched controls were chosen complaining from
      dyspeptic symptoms but with completely normal by upper endoscopic examination.
      The patients and controls were selected from Mataria Teaching Hospital and Ain
      Shams Specialized Hospital in Cairo and subjected to complete history taking,
      clinical examination, endoscopic examination and biopsy from the lower end of
      esophagus for examination of the presence of Helicobacter Pylon. No causal
      association between infection with Helicobacter pylon and the development of
      (GERD) could be demonstrated. It is highly recommended to further investigate
      this association in patients with grade IV esophagitis (Barrett's esophagus)
      only.

PMID- 17216947
TI  - Effect of food preservatives on mother rats and survival of their offspring.
AB  - This work aimed to investigate the effect of food preservatives (sodium benzoate
      and sodium nitrite) on biochemical aspects of mother rats and survival of their
      offspring. Fifty pregnant albino rats (Sprague Dauley strain) were divided into 5
      groups (10 rats each) and kept individually in wire cages. The first group was
      fed standard diet free from any additives (control group). The second and third
      groups were fed standard diet with added acceptable and high doses of sodium
      benzoate as a preservative. The fourth and fifth groups were fed on standard diet
      containing sodium nitrite at the same levels like that for benzoate in the second
      and the third groups. Animals were fed ad libitum during pregnancy. After
      delivery, the pups were measured anthropometrically (weight and length) and the
      mothers were sacrificed and their blood samples were taken from the hepatic
      portal vain. Serum was separated and subjected to biochemical analysis. The
      results indicated that sodium nitrite intake was associated with a significantly
      decreased food intake and lowered hemoglobin and hematocrit values (p<0.01 each)
      while their serum AST and ALP showed significantly higher values (p<0.01).
      Mothers receiving high dose of benzoate had significantly high ALT values
      (p<0.01). Both levels of benzoate and nitrite were shown to induce decrease in
      serum bilirubin and increased serum urea, while the high and acceptable doses of
      benzoate induced higher values of serum uric acid (p<0.01 and p<0.05,
      respectively), but did not induce a significant increase in serum creatinine.
      Pregnant rats which received acceptable and high doses of nitrite showed an
      increased mortality rate of their pups. The mean weight and length of live pups
      were lowered by food preservatives compared with controls.

PMID- 17216948
TI  - Application of reverse transcriptase-polymerase chain reaction for detection of
      Rift Valley Fever viral antigen from mosquito.
AB  - A reverse transcriptase polymerase chain reaction (RT-PCR) was applied to detect
      Rift Valley Fever Virus (RVFV) in Culex pipiens mosquito pools collected from
      Alexandria and Behira governorates of Egypt (50 pools each). All mosquito pools
      were subjected to double sandwich enzyme linked immunosorbent assay (ELISA)
      technique to detect RVF viral antigen. Out of all 100 mosquito pools, only
      18(18%) were positive by ELISA, 10(20%) out of 50 pools were positive in Behira
      governorate and 8(16%) were positive in Alexandria governorate. All positive
      samples (18) in addition to two negative samples (one was used as a negative
      control and the other was used as a positive control after addition of 1.0 ml. of
      103 inactivated RVF virus) were subjected to RT-PCR. Out of these 18 positive
      samples by ELISA, only 7(38.89%) were positive for RVF Virus by RT-PCR. These
      results gave the possibilities of existence of other phleboviruses that cross
      react with RVF Virus.

PMID- 17216949
TI  - Microbial evaluation of some heat treated turkey products at different processing
      stages.
AB  - Random samples at the three processing stages of turkey keshta, turkey rosto,
      turkey luncheon and turkey frankfurter (20 samples for each stage were
      collected). For luncheon and frankfurter, 20 samples of each of thighs and breast
      represents the 1 st stage of processing were also taken. These samples were
      obtained from some meat processing plants at Alexandria province to make a total
      of 280 samples. The samples were examined microbiologically and the results
      revealed that, the total aerobic bacterial count in the examined Keshta and rosto
      shows their highest count in the 1st stage and gradually decreased in the 2nd and
      3rd stages. On the other hand, the total aerobic bacterial count in luncheon and
      frankfurter samples slightly increased in the 2nd stage and then decreased in the
      3rd stage. The Coliform count also shows its highest count in the 1st stage and
      decreased in the 2nd stage and could not be detected from the 3rd stage of keshta
      and rosto samples, while it increased slightly in 2nd stage and could not be
      detected in the 3rd stage for luncheon and frankfurter samples. E. coli and
      Staphylococcus aureus were higher in the 1st stage than in the 2nd stage of
      processing of the examined keshta and rosto samples while they were higher in the
      2nd stage than in the 1st one in luncheon and frankfurter samples but could not
      be detected from the 3rd stage in all products. Both Clostridium perfningens and
      Salmonella could not be detected in the examined turkey products at the different
      processing stages. The total mould and yeast counts in the examined products
      showed highest count in the 1st stage and decreased in the 2nd stage and could
      not be detected in keshta and rosto in 3rd stage while in frankfurter samples the
      counts in the 1st and 2nd stages were nearly the same and decreased in the 3rd
      stage but in luncheon samples the count was slightly increased in the 2nd stage
      and not detected in the 3rd stage. The public health significance of
      microorganisms as well as the suggested hygienic measures in order to improve the
      quality of the examined turkey products were discussed.

PMID- 17216950
TI  - Mercury, cadmium and lead levels in Bagrus bayad fish from the river Nile, Delta
      Region, Egypt.
AB  - A total of 50 random samples of Bagrus bayad were collected from various
      localities of River Nile at lower Egypt and were analyzed for determination of
      Hg, Cd and Pb concentrations by AAS. The obtained results revealed that the
      concentrations of Hg, Cd and Pb in fish muscles were ranged from 0.026 to 0.391,
      0.028 to 0.053 and 0.022 to 0.654 with mean +/- SE values of 0.190 +/- 0.017,
      0.048 +/- 0.003 and 0.215 +/- 0.047 microg/g wet weight, respectively. 24% and 6%
      of the examined fish samples exceeded the maximal permissible limit set by
      FAO/WHO (1992) for Cd and Pb, respectively. Whereas none of the examined samples
      exceeded the maximal limit for Hg. The possible health hazards of heavy metals as
      well as the suggestive measures for minimizing the pollution of fish and water
      had been discussed.

PMID- 17216951
TI  - Parasitological profile of the surveyed population for malaria in an endemic area
      in Faiyoum Governorate, Egypt.
AB  - Egypt represents the only focus in the Mediterranean region where Plasmodium
      falciparum transmission still occurs. A longitudinal parasitological study has
      been implemented (September 1995 to December 1996) in Faiyoum, Egypt. A total of
      9065 blood slides for malaria parasites were taken from all people in the study
      area as mass blood examination (MBE); those attending the malaria unit as passive
      case detection (PCD) as well as from neighborhood of the detected cases (NOD).
      They were stained by Giemsa stain and examined under standard conditions for
      positivity, parasite species and parasite density. Our results show that MBE
      detected 61.5% of malaria cases while 23.1% and 15.4% of the confirmed cases were
      detected through PCD and NOD respectively. The overall parasite rate was 5.7/1000
      examined population. P. falciparum was the most predominant species (96.1%),
      followed by P. vivax (3.9%). The epidemiological factors causing the persistence
      of malaria transmission in the study area are discussed.

PMID- 17216952
TI  - Evaluation of the effectiveness of routine measles vaccination: case-control
      study.
AB  - A retrospective case-control study was conducted in two primary schools located
      in eastern region of Cairo to evaluate the protective value of routine measles
      vaccination. A total of 230 children who had a previous measles illness were
      identified over 3 months period. Each case was matched to two controls based on
      age and sex. Vaccination status of the study children was ascertained through
      reviewing vaccination certificates The overall measles vaccine effectiveness was
      estimated at 53% (95% CI 71%-26%) There was an association between age of measles
      vaccination and vaccine effectiveness (VE) Primary vaccination failure due to
      young age of measles vaccination is the likely explanation of the low measles
      vaccine effectiveness. Adoption of two-dose measles vaccination policy with the
      second dose being given at older age needs to be considered to correct the
      problem of vaccine failure.

PMID- 17216953
TI  - The prevalence of antibodies to hepatitis C virus in Hail region, Saudi Arabia.
AB  - The prevalence of subjects positive for anti-HCV antibodies was studied at Hail
      region Kingdom of Saudi Arabia (KSA). The study involved 8862 subjects tested for
      anti-HCV antibodies at King Khalid General Hospital during the years 1994-Using
      Elisa, a total prevalence of 5.09% positive subjects was found. The disease is
      shown to be mainly acquired at school age and adulthood. Unlike hepatitis B
      virus, vertical transmission among preschool children does not seem to have an
      important role in transmission of HCV virus. Egyptians had a high prevalence of
      26% as compared to other expatriates. Blood donors had a prevalence of 4.3% which
      is higher than that reported from other regions in Saudi Arabia. Medical staff
      had a prevalence rate of 2.2% indicating a relatively low risk of infection.
      Dialysis patients had a prevalence of 6.9% which is lower than that reported from
      other regions in Saudi Arabia. The higher prevalence of HCV infection in Hail
      (which has a lower socioeconomic status) compared to those in Riyadh and Eastern
      province suggests the possibility of other modes of transmission.

PMID- 17216954
TI  - Effect of non nutritive sucking on the behavioral state and physiological change
      in premature infants before feeding.
AB  - Premature infants display few behaviors that provide quantitative information
      about their maturational development, making it difficult to carry out
      appropriate care. This study was performed to investigate the effect of non
      nutritive sucking on behavioral state and physiological changes in premature
      infants. They were selected from premature unit of Main University Hospital at
      Tanta city. Forty premature infants were divided into two groups, nonnutritive
      sucking and no non-nutritive sucking. Personal characteristics were obtained from
      medical records. Anderson Behavioral State Scoring Systems were used and observed
      four times daily. Physiological changes were noticed; temperature, heart and
      respiratory rates The present study revealed that the time spent in sleep states
      was decreased and time spent in awake states was increased, when compared to no
      non-nutritive sucking group (ONNS). There was Statistically significant
      differences within the two groups related to behavior states and physiological
      changes. The development of sucking reflex was accelerated among premature in the
      non-nutritive sucking group. They shift earlier to oral feeding and their
      discharge was earlier.

PMID- 17216955
TI  - Schistosoma mansoni infection and cognitive functions of primary school children,
      in Kafr El Sheikh, Egypt.
AB  - There is growing concern that parasitic infection may detrimentally affect
      children's mental function. In this study our main objective was to investigate
      the effects of schistosoma mansoni infection on cognitive functions of school
      children aged 9-12 years in Kafr El Sheikh Governorate. Out of 2601 children
      screened parasitologically, 60.7% were S. mansoni positive. Children recruited
      for the case-control study were 40 with light S. mansoni infection (<100 epg), 40
      with heavy infection (>400 epg) and 40 parasite-free served as control. All
      children were subjected to the Arabic Version of Wechsler Intelligence Scale for
      Children (WISC) and the Verbal Fluency Test. Though, the general IQ scores of
      infected children were insignificantly lower than their controls, yet they
      recorded a significantly lower performance IQ as well as, poorer performance on
      comprehension, vocabulary and picture completion subtests. Implications for
      preventive measures will be discussed.

PMID- 17216956
TI  - Autoantibodies to neurofilaments (NF), glial fibrillary acidic protein (GFAP) and
      myelin basic protein (MBP) in workers exposed to lead.
AB  - An expanded follow-up assessment of the autoantibody response to neuronal and
      astroglial autoantigens (NF68; NF160; NF200; MBP; GFAP) as early markers of
      neurotoxicity was performed in male workers exposed to lead (Pb) of a battery
      factory (n=50) and a matched reference group (R) of workers at a food packing
      plant (n=39). Mean age, years of exposure and blood lead (PbB ug/dl) (+/-SD) for
      lead and R, respectively, were: Age:39 +/- 6; 41 +/- 7; Yrs. Exposed: 14 +/- 6:0;
      PbB: 32 +/- 11: 16 +/- 5 percent with detectable titers to nervous system
      proteins in the Pb and R populations, respectively, were: Anti-NF68: 59; 17; Anti
      NF160: 28; 15; Anti-NF200: 25; 0; Anti-GFAP: 90; 20; Anti-MBP: 16; 4.
      Autoantibodies to nervous system proteins predominated in workers occupationally
      exposed to Pb compared to R. Anti-NF68 and GFAP titers were the most frequently
      encountered. Anti-NF68 titers were significantly correlated with years of
      exposure (r = 0.538, p < 0.0001) and with PbB (r=0.325, p < 0.05). Furthermore,
      the number of detectable autoantibody types correlated with clinical scores of
      sensorimotor deficits (r = 0.459, p < 0.0001). This study suggests that
      autoantibodies provide a promising biomarker of neurotoxicity while providing
      information on subcellular targets. It also raises concerns of toxicant-induced
      autoimmune neuropathy.

PMID- 17216957
TI  - Developing and testing of an Egyptian version of Children's Health Locus of
      Control scale.
AB  - The purpose of this study is to develop and test the reliability and validity of
      an Egyptian version of the Children's Health Locus of Control scale. A cross
      sectional study design was applied using a stratified random sample of 930
      students from the final two grades of primary and all grades of the preparatory
      schools. A further convenience sample of 120 students was selected to examine
      test-retest reliability of the scale. A preliminary instrument was developed and
      consisted of 40 statements having one of two response forms; a Yes/No format and
      a 4-point Likert scale format From data analysis the later format showed higher
      validity and reliability than the former one. Construct validity of the scale is
      evidenced by the factor analysis which revealed five factors (Internal, Chance,
      Powerful Others, Fate and Self blame) consistent with the previous theoretical
      model of HLC. As indicated by eta coefficient the scale and the subscales showed
      strong discriminating power between subjects. The known group comparison
      indicated a good criterion validity of the scale and the subscales. The scale
      showed a considerable reliability as alpha coefficient was 0.73 with test-retest
      reliability of 0.65. Comparison of different groups of students indicated that
      the scale could be used with confidence for all age groups, though it was more
      reliable for the preparatory phase, for private and governmental schools for
      males and females and for different social strata. Further testing of the
      developed scale is indicated among Egyptian children in different cultures.

PMID- 17216958
TI  - Epidemiological study of the claimed zinc phosphide intoxication in Kom Ombo
      district April 1996.
AB  - INTRODUCTION: In April 1996, in Aswan Governorate, Egypt, an outbreak of vomiting
      without diarrhea, abdominal and leg pain was reported. METHODS: A case-control
      study was conducted to determine the cause of the outbreak. 25 cases who had
      vomiting without diarrhea, abdominal and leg pain. Controls were randomly chosen
      from adjacent houses to cases and another village. RESULTS: No occupational
      exposure was associated with the disease, 84% of cases lived in households where
      chemical rodenticide had been used for rat infestations compared to 22% of
      controls. Laboratory analysis and field investigation identified zinc phosphide
      intoxication as the probable cause of this outbreak.

PMID- 17216959
TI  - Comparative study on different recent diagnostic and therapeutic regimens in
      acute typhoid fever.
AB  - Forty five positive blood culture acute typhoid cases were studied during a 2
      years period (1997-1999) in Abbassia Fever hospital, Cairo, Egypt. Their ages
      ranged between 4-23 (12 +/- 2.5) years. Male: Female ratio was 1:1. Three of the
      4 classical signs namely: toxic look (84%), bronchitic chest (47%), tumid
      tympanitic abdomen (84%) and just palpable receding spleen (69%) were found in
      almost all cases and offer a good bed side clinical diagnostic test. Blood
      picture revealed anaemia, within normal white blood count and thrombocytopenia.
      Liver function tests showed within normal total serum bilirubin, two or more
      folds increase of ALT and within normal serum alkaline phosphatase. Comparing the
      3 tests, namely significant Widal titre (56%), modified Widal test (89%) and
      bright spleen (78%), it was found that modified Widal test is the most sensitive
      serological test. Ultrasonographic finding of bright spleen is an easy, safe,
      noninvasive and sensitive technique which is relatively cheap. Each of the 3
      drugs in our study namely chloramphenicol, quinolones and ceftriaxone resulted in
      improvement of general condition, drop of fever, increase in haemoglobin, white
      blood count and platelet count. Also, there was a significant improvement of
      liver function tests by either of the 3 drugs. Ceftriaxone is the best drug from
      the clinical and laboratory points of view followed by quinolones in multidrug
      resistant (MDR) acute typhoid cases. Chloramphenicol is still the drug of choice
      in chloramphenicol sensitive salmonellae.

PMID- 17216960
TI  - Knowledge and perception of professionals towards school injuries.
AB  - As injuries remain a threat to children everywhere including school, this study
      was undertaken to reveal the knowledge and perceptions of school physicians,
      nurses, teachers and social workers regarding school injuries. To accomplish this
      aim, all school-based clinics operated by a physician were identified. All
      physicians and nurses were included in this survey. In addition, a teacher or a
      social worker was randomly selected from the same school. They were requested to
      fill in a questionnaire to collect relevant information. Findings indicate that
      school injury is not perceived as a priority problem by all social workers and
      68.5% of teachers. Moreover, its economic burden was not perceived by one third
      of physicians and nurses. Regarding associated risk factors, more than 80% of the
      surveyed professionals recognized nine out of the 16 stated factors as a risk for
      school injuries. However, less than 80% viewed that the risk of school injury is
      higher in technical schools, schools which include more than one educational
      stage as well as in the evening shift. Moreover, less than 80% of nurses
      recognized that a higher risk is associated with poorly kept school building,
      primary schools and methods of transportation. Furthermore, less than 80% of
      teachers recognized that boys are at a much higher risk of injuries. Surveyed
      professionals ranked increase supervision, continuous maintenance of school
      building as well as health education activities as priority preventive
      strategies. Mass media was the method of health education that received the
      highest priority while the least were pupils' activities and the organization of
      an injury prevention day. It can be concluded that, school professionals,
      exceptionally teachers and social workers need to be aware of the extent of
      school injuries and the risks associated with their occurrence. Such awareness is
      the key issue in ensuring the safety of children while they are at school.
      Moreover, it is indispensable for the planning and implementation of effective
      preventive strategies. They should also recognize that pupils' involvement is a
      highly effective mean of creating awareness about safety and to encourage them to
      take the responsibility of their safety as well as that of other pupils.
      Organized training programs directed to all personnel in the area of school
      injuries are deemed essential.

PMID- 17216961
TI  - Genetic determinants of essential hypertension.
AB  - This study aimed at determining the role of genetic and environmental risk
      factors in the development of essential hypertension in Alexandria, Egypt. A case
      control-study was conducted in the Main Health Insurance Hospital, (MHI)
      Alexandria, Egypt, whereby cases previously diagnosed as hypertensive were
      included in the study. A hospital-based control group visiting the hospital for
      other unrelated conditions and randomly selected in the same day as cases was
      also included in the study. Both cases and controls were subjected to a semi
      structured questionnaire including information concerning socio-demographic data
      and risk factors for hypertension Only cases were subjected to segregation
      analysis. This study included 165 cases with history of essential hypertension,
      and 196 controls. Multivariate analysis of potential risk factors showed the
      following factors to be independently associated with an increased risk of
      essential hypertension: age over 40 years, elevated BMI, workers, ever smoker and
      stress. Education less than 6 years remained in the model as an independent
      protective effect. Segregation analysis proved that the disease is not inherited
      as single gene mode of inheritance. On the other hand, the heritability for 1st,
      2nd and 3rd degree relative was 28.2%, 28.7% and 20.0%. These figures provide
      evidence to multifactorial mode of inheritance in essential hypertension.

PMID- 17216962
TI  - Prevalence of proteinuria and its clinical implications in type 2 diabetic
      patients treated at a primary health care centre in Abha City.
AB  - The aim of the present study is to describe the prevalence of proteinuria in a
      series of type 2 diabetic patients registered and followed up in the diabetes
      clinic of a primary health care center (PHCC) in Abha city, southern Saudi Arabia
      and to relate the proteinuria to some clinical manifestations. The study involved
      the files of 208 diabetic patients (118 females and 90 males). They were chosen
      from 475 files of diabetic patients receiving care in the PHC center of Shamasan
      in Abha City. The selection was based on the fulfillment of certain criteria:
      type 2 diabetic patients, registered for at least 12 months and visited the
      clinic for at least once during that period. For each patient the diabetes
      duration, the last readings of fasting blood sugar, total cholesterol level, were
      used. Proteinuria was considered whenever the last and any of the preceding 3
      urine analysis revealed it by the dipstick test. Proteinuria is present in more
      than half the patients (54.3%). The fasting blood sugar shows a considerably high
      mean of 218.0 +/- 72.0 mg/dl. The total cholesterol level on the other hand
      showed a slight high average of 233.7 +/- 55.2 mg/dl. The results of the three
      different types of compliance as scored by the treating physician showed that the
      poor scores dominate with 74%, 82.7% and 78.4% of patients' diet, drug and
      appointment compliances. The outcome of the logistic regression model for
      proteinuria showed that the significant factors were the poor glycemic control
      with an odds ratio (OR) of 3.13, diabetes duration (OR = 1.08 for every year) and
      diastolic blood pressure (OR = 6.11). Diabetic patients treated in the PHC level
      should be regularly monitored for microalbuminuria and not gross proteinuria to
      prevent progression to overt nephropathy which will eventually lead to ESRD. The
      risk increases with poorly controlled and hypertensive patients.

PMID- 17216963
TI  - The effect of nutritional intervention program on the prevalence of anemia among
      pregnant women in rural areas of Belbis district-Sharkia Governorate-Egypt.
AB  - OBJECTIVE: to determine the prevalence of anemia among pregnant women in rural
      areas of Belbis district, Sharkia Governorate, Egypt, and to assess the effect of
      iron supplementation and nutritional educational program on the level of
      hemoglobin in blood. DESIGN: A cross-sectional study was conducted followed by
      intervention prospective study. SUBJECTS: Women attended the antenatal clinics in
      two primary health care units of Belbis district through December 2000, which
      amount to 100 women 50 in each primary health care unit. Data was collected as
      regard to their age, parity, educational level and occupation. All participating
      women were subjected to hemoglobin analysis during the first time, after one
      month and two months. Women with hemoglobin level less than 11 gm/dl were
      considered anemic. STATISTICAL ANALYSIS: Chi-square and "t" tests (paired and
      unpaired) were applied to test the relationships among study variables. RESULTS:
      The prevalence of anemia among pregnant women at the first time booking was 55%.
      After the intervention nutrition education program and iron supplementation the
      prevalence declined after three months down to 32%. While the prevalence after
      the same period for pregnant women in the control group (non intervention group)
      was 46%. Both parity and educational level affected significantly the prevalence
      of anemia only among the intervention group. This study suggests that anemia is
      still high among pregnant women and integrated intervention programs should be
      considered prior to conception.

PMID- 17216964
TI  - Quality of nursing care provided in a neonatal intensive care unit. Structure
      assessment.
AB  - Structure is considered one of the three major approaches to the evaluation of
      quality the other two being process and outcome. Appraisal of structure involves
      the attributes of the settings in which care is delivered that includes the
      material resources, the human resources, and the organizational structure. The
      aim of the study was to assess the quality of nursing care provided at tne
      neonatal intensive care unit (NICU) at Princess Badia Teaching Hospital, Jordan,
      as regards the various components of structure domain within the context of
      quality. A checklist for structure assessment was developed which included
      criteria classified under three main areas namely, material resources, human
      resources, and organizational structure. Results revealed certain deviations from
      the recommended compliance scores for each area. Recommendations were proposed to
      stress the importance of the NICU being specifically built to reflect practice,
      environment, and cultural needs, as well as continuous education activities of
      NICU staff. Documented policy and procedure manuals were also recommended for
      assuring maintained quality care at the NICU.

PMID- 17216965
TI  - Indoor air quality of schools in Alexandria City.
AB  - Poor air quality in schools can affect children's desire and ability to
      concentrate and learn and may lead to increased rate of absenteeism. This study
      was carried out with the aim of characterizing and measuring indoor air quality
      in school buildings, measuring ventilation status and studying the impact of
      design and environmental parameters on some measured pollutant levels. The study
      was carried out in some primary schools of Alexandria City. All ventilation rate
      levels exceeded the ASHRAE standard of 15 cfm/pupil except for a few cases. Badly
      located and small window area led to air stagnation and low ventilation rates.
      Levels of TSP greatly exceeded a suggested daily guideline of 150 microg/m3. The
      highest average levels of TSP were found inside classrooms surrounded by unpaved
      playground and located near semi rural, commercial and heavy traffic areas, while
      lowest levels were in classrooms located next to residential areas. The average
      total bacteria were highest in winter. There was also a slight increase in
      respiratory symptoms and signs in winter. There was a significant positive
      correlation between average total, pathogenic and non-pathogenic bacteria with
      average TSP levels, indoor CO2 levels and relative humidity while a significant
      negative correlation was observed with ventilation rate and class volume
      occupied. The average attack rate of respiratory conditions was 1.96 episode per
      child. Running nose was the highest frequent symptom. Students of first grade,
      had an incidence rate higher than that among fifth grade students.

PMID- 17216966
TI  - A prediction model for the incidence patterns of female breast cancers in
      Alexandria, Egypt.
AB  - Breast cancer is the most common cancer among women in the world. Female breast
      cancer incidence has historically increased all over the world during the past
      decades. The purpose of this study was to estimate the patterns of female breast
      cancer incidence in Alexandria, Egypt, from 1972 to 2001. An up-to-date
      perspective systematically collected data on the incidence of female breast
      cancers was used. Age categories-estimated incidence over the 30 years period
      were computed. Time series analysis showed that incidence of breast cancers is
      increasing significantly during the studied period. Linear trend model was best
      fitted, with the studied interval and the estimated cancer cases per year taken
      into account. Age-incidence correlation showed a high correlation between age
      group of 40-50 years old and incidence. Analysis of the patterns for cancer
      incidence indicates that the highest occurrence of female breast cancer is shown
      in the age category of 45-50 years followed respectively by the age categories of
      40-45 years, 50-55 years, 35-40 years and then 55-60 years. These findings
      support the growing body of evidence from female breast cancer incidence
      suggesting that age is a well-known risk factor for breast cancer susceptibility.

PMID- 17216967
TI  - Water treatment plants assessment at Talkha power plant.
AB  - Talkha power plant is the only power plant located in El-Mansoura. It generates
      electricity using two different methods by steam turbine and gas turbine. Both
      plants drew water from River Nile (208 m3 /h). The Nile raw water passes through
      different treatment processes to be suitable for drinking and operational uses.
      At Talkha power plant, there are two purification plants used for drinking water
      supply (100 m3/h) and for water demineralization supply (108 m3/h). This study
      aimed at studying the efficiency of the water purification plants. For drinking
      water purification plant, the annual River Nile water characterized by slightly
      alkaline pH (7.4-8), high annual mean values of turbidity (10.06 NTU), Standard
      Plate Count (SPC) (313.3 CFU/1 ml), total coliform (2717/100 ml), fecal coliform
      (0-2400/100 ml), and total algae (3 x 10(4) org/I). The dominant group of algae
      all over the study period was green algae. The blue green algae was abundant in
      Summer and Autumn seasons. The pH range, and the annual mean values of turbidity,
      TDS, total hardness, sulfates, chlorides, nitrates, nitrites, fluoride, and
      residual chlorine for purified water were in compliance with Egyptian drinking
      water standards. All the SPC recorded values with an annual mean value of 10.13
      CFU/1 ml indicated that chlorine dose and contact time were not enough to kill
      the bacteria. However, they were in compliance with Egyptian decree (should not
      exceed 50 CFU/1 ml). Although the removal efficiency of the plant for total
      coliform and blue green algae was high (98.5% and 99.2%, respectively), the
      limits of the obtained results with an annual mean values of 40/100 ml and 15.6
      org/l were not in compliance with the Egyptian decree (should be free from total
      coliform, fecal coliform and blue green algae). For water demineralization
      treatment plant, the raw water was characterized by slightly alkaline pH. The
      annual mean values of conductivity, turbidity, and TDS were 354.6 microS/cm,
      10.84 NTU, and 214.6 mg/I, respectively. There was an increase in the results of
      conductivity, turbidity, total hardness, and TDS in carbon filter effluent which
      was attributed to the desorption of adsorbed ions on the carbon media. The
      removal efficiencies of turbidity, total hardness, and TDS indicated the high
      efficiency of the cationic filter. The annual removal efficiencies of
      conductivity, turbidity, chloride, and TDS proved the efficiency of the anionic
      filter for removing the dissolved and suspended ions. All of the recorded values
      of the pH, conductivity, turbidity, chlorides, hardness, and TDS of the mixed bed
      effluent indicated that the water at this stage was of high quality for boiler
      feed. The study recommended adjustment of coagulant and residual chlorine doses
      as well as contact time, and continuous monitoring and maintenance of the
      different units.

PMID- 17216968
TI  - Foot and mouth disease (FMD): serological investigation in some farms of
      Alexandria Governorate of Egypt.
AB  - Suspected cases of Foot and Mouth disease (FMD) in cattle were noted in some
      farms of Alexandria governorate during the period from January to March 2000. The
      investigated cattle suffered from oral and foot lesions associated with lameness
      in addition to fever in some and inappetance in others. At the same time the
      contact workers and veterinarian suffered from fever, during the course of the
      disease in cattle. Blood samples were withdrawal from suspected cases of cattle
      (31 cases), and from 24 contact cases. Saliva and vesicular lesions of the tongue
      were taken on glycerol buffer saline for isolation and serotyping of FMD virus by
      hyperimmune sera. The virus was isolated from all saliva and vesicular lesions of
      the diseased animals and serotyped as FMD O1. A total of 30 (96.77%) out of 31
      suspected cases, while it was only 10 (41.67%) out of 24 contact cases were
      positive by ELISA for anti-FMD antibodies. Also 25 blood samples were withdrawal
      from contact persons with diseased animals and were suffered from fever, while 25
      blood samples were taken from contact persons but not suffered from fever while 5
      blood samples were taken from persons were not in contact with any veterinary
      source (Children) and were used as negative control. A total of 13 (52%) out of
      25 and 2 (8%) out of 25 were positive for anti-FMD antibodies from diseased and
      contact persons respectively.

PMID- 17216969
TI  - Hypertension in Oman: distribution and correlates.
AB  - BACKGROUND: International studies have reported increased prevalence of
      hypertension and other cardiovascular risk factors, Our aim was to study the
      distribution and the correlates of hypertension (HTN - systolic or diastolic) in
      a community based survey (National Health Survey, 2000). METHODS: A cross
      sectional survey of the health status of Omani community was designed. Face to
      face interview including demographic data, blood pressure measurement, fasting
      blood glucose and serum cholesterol, weight, height, waist and hip measurement
      for 7011 Omani subjects with a response rate ranging between about 83% (for
      fasting blood glucose) to about 91% (for blood pressure measurement). RESULTS:
      The crude prevalence of HTN was 33.1%, while the age-adjusted prevalence was
      38.3%. Older age groups, male gender, lower level of education, non- working,
      hypercholestremia, being married, obese, smoker, or having abnormal Waist Hip
      Ratio (WHR), or Total Impaired fasting glucose (TIFG) were found to be associated
      with hypertension in bivariate analysis. Logistic models were run to identify the
      adjusted Odds Ratio for the overall sample, for separate genders and age groups.
      For the overall sample, subjects aged 60 and above were 5.4 times more likely to
      be hypertensive than those below forty. Female gender was a protective factor in
      the overall sample, while it increased the risk by 1.4 times among those aged
      60+. Obese or centrally obese subjects were also more likely to be hypertensive.
      Subjects with impaired fasting glucose, diabetes, or hyperchlosteremia were more
      likely to have hypertension than others in the majority of the logistic
      regression models. CONCLUSION: Hypertension is considered a major public health
      problem in Oman. Increasing the awareness of both health care providers and the
      community is crucial.

PMID- 17216970
TI  - Job satisfaction and stress among MCH physicians in Alexandria.
AB  - Physician satisfaction with their job is a topic of importance to physicians in
      practice, physicians in training, health administrators, and health executives.
      Stress among physicians arises due to inadequate demands of the job in relation
      to worker's abilities, frustrated aspirations, and dissatisfaction with regard to
      aimed goals. The cross-sectional study design was conducted at 7 randomly
      selected Maternal and Child Health (MCH) centres, affiliated to seven medical
      zones in Alexandria. The study sample consisted of all physicians working at the
      studied MCH centres. A questionnaire designed for data collection was distributed
      to all physicians available and who accepted to participate in the study. The
      questionnaire included 4 sections measuring, socio-demographic characteristics,
      overall satisfaction and global satisfaction, an eight-dimension satisfaction
      scale, and a four-dimension stress scale. The questionnaire was distributed to
      100 physicians out of whom 77% responded. Satisfaction scale was on a scale
      ranging from 6 (greatly satisfied) to 1 (greatly dissatisfied). Stress was on a
      scale ranging from 6 (greatly stressed) to 1 (greatly unstressed). The total mean
      satisfaction score for the sample under study was 3.3 +/- 0.6 with a significant
      difference among zones (F = 4.4, p < 0.05), and the total mean stress score for
      the sample under study was 3.8 +/- 0.7 with a significant difference among zones
      (F = 2.4, p < 0.05). It is recommended that decision makers at the MOHP find ways
      to raise the physicians' pay, efficient planning of resources, and find
      opportunities for future promotion.

PMID- 17216971
TI  - Health promotion activities among working and non-working adult women.
AB  - Self report measures of health promotion activities and demographic variables of
      working women and housewives were analyzed. A sample of 516 female clients (283
      of housewives and 233 of working women) were chosen from nine different out
      patient clinics offering health services to women in Tanta city. Three structured
      questionnaire sheets were used, namely: (1) Health promoting life style
      questionnaire (HPLQ), (2) Health value scale (HVS), and (3) self-efficacy. The
      results showed that a minority of housewives and working women groups correctly
      tended to practice more health promotion activities. However, the total mean
      scores of working women were slightly higher ( 362.03 +/- 33.55 out of 522) than
      that among housewives group (332.77 +/- 31.18). Multiple regression analysis
      indicated a significant correlation between women scores regarding most of the
      studied items related to self reported health promotion activities and
      demographic variables. Higher education (p = 0.004), family income (p = 0.005),
      and duration of marriage (p = 0.031) were associated significantly with working
      women who sought more health promotion activities, while education (p = 0.003)
      and family income (p = 0.028) were associated significantly with housewives
      group. Finally, the present study proved that work of women (p = 0.000)
      significantly related to the practice of health promotion behaviors.

PMID- 17216972
TI  - Patterns in the incidence of pediatric cancer in Alexandria, Egypt, from 1972 to
      2001.
AB  - Cancer among children is a substantial public concern. The epidemiology of
      childhood cancer is not fully understood. The descriptive epidemiology for cancer
      incidence has been a subject of considerable debate in order to identify and
      clarify the role of etiological factors and environmental exposure in cancer. An
      up-to-date perspective systematically collected data on the incidence of
      childhood cancer in Alexandria was used. Statistical analysis revealed that the
      over all cancer incidence rate increased from 1972 to 2001. The incidence of
      lymphatic and haemopoietic cancers increased dramatically over the specified
      period. The lymphatic and haemopoietic ancer incidence in 2001 have increased
      approximately 11 times cancer incidence in 1972. The incidence of leukemia among
      infant less than 5 years increased exponentially with a higher incidence among
      boys. Little increase was observed in the cancers of oral cavity, digestive
      organs and respiratory system over the specified period. Incidence of genito
      urinary cancers have increased 3.7 times cancer incidence in 1973. Brain and
      central nervous system cancers showed an increase of 4.5 fold during the 30 years
      studied period. The trends in some cancer types suggest the need of a closer
      examination of the underlying factors and environmental contaminants leading to
      the disease in children.

PMID- 17216973
TI  - The under-use of steroids for children with asthma in southwestern Saudi Arabia.
AB  - Recent surveys have shown that asthma management is still not optimal. The aim of
      this study was to investigate how far corticosteroids and other medications are
      used for children with asthma visiting the emergency room (E.R) for management.
      The study sample comprised the128 children, who visited the emergency rooms of
      Assir central Hospital and Abha Private Hospital, and received treatment for
      their asthma from august 1997 to 31 June 2002. Information upon asthmetic
      patients were collected from records, regarding the previous medicines received
      prior the emergency visit and the treatment received at emergency room. Only
      children with age between one year and twelve years who were discharged from the
      emergency rooms, were included in this study. The striking finding in this study
      is that, less than one tenth of the patients were given intravenous steroids;
      four patients were given oral steroids, while none of them was given
      intramuscular steroids at emergency room. Also more than half of the patients
      received anti- cough medicine, and two thirds of patients were given antibiotics.
      Therefore, the under use of steroids and over use of other medicines for patients
      with acute asthma is very clear in this study. Specific education programmes
      focusing on the increase of prescription rate and adherence to steroids, will
      improve the overall degree of asthma

PMID- 17216974
TI  - Knowledge, attitudes and practices of women towards antenatal care: rural-urban
      comparison.
AB  - Pregnancy is a period at which a woman's health is placed at risk. However,
      health care professionals providing antenatal care (ANC) can reduce that risk by
      monitoring women' health regularly arid offering both preventive and curative
      services. Worldwide, an estimated 515,000 women die of pregnancy-related causes,
      a rate of over 1,400 maternal deaths each year. The overwhelming majority of
      these deaths and complications occur in developing countries. Effective ANC,
      appropriate emergency treatment of complications and competent referral level
      encompass the most effective answers to reduction of maternal deaths. Data
      related to rural/urban difference concerning knowledge, attitudes and practices
      of women towards ANC in Alexandria are lacking. The present study is aimed at
      comparing knowledge, attitudes and practices towards ANC between rural and urban
      women in Alexandria and also, to identify certain related factors. A cross
      sectional, community- based house-to-house survey was conducted in Alexandria
      using cluster-sampling technique (30 clusters from urban areas and30 clusters
      from rural areas). Each cluster consisted of 5 women who had given birth within
      the last 2 years preceding the survey. Urban women had a higher mean total score
      for their knowledge on ANC than their counterparts of rural women, with a
      statistical significant difference (11.23 +/- 2.91 and 6.59 +/- 4.14,
      respectively and Z = 9.73, P < 0.001). Also, Urban women had a significantly
      higher mean total score for their attitudes towards ANC compared to the rural
      women (10.66 +/- 2.33 versus 8.55 +/- 2.39, P < 0.001). Concerning maternal
      practices, the current study revealed rural/urban disparities as significantly
      higher proportions of urban women had proper practices during antenatal period in
      their last pregnancy as regards utilization, earlier initiation and frequent
      visits of antenatal care. On the other hand, nearly half of urban women (45.3%)
      had not been vaccinated during their last pregnancy compared to only 24.7% of
      rural ones, (P < 0.001).

PMID- 17216975
TI  - Assessment of safety of frozen foods.
AB  - This study aimed to assess the microbiological quality of 90 frozen food samples
      (50 samples of raw frozen vegetables including molokeya, okra, green peas, peas +
      carrot, and artichoke, 20 of frozen poultry products and 20 of frozen meat
      products), and to assess the level of women practice during handling. A cross
      sectional study was conducted. Results showed that the mean aerobic mesophilic
      plate count of frozen vegetables was 3.4 x 10(5) +/- 7.3 x 10(5) cfu/g. The mean
      mold and yeast count was 3.9 x 10(3) +/- 1.1 x 10(4) cfu/g. The mean coliform
      count was 3.9 x 10 +/- 6.6 x 10 m.o./g. In case of meat product, the mean aerobic
      count was 2.3 x 10(5) +/- 3.2 x 10(5), that of mold and yeast was 2.5 x 10(5) +/-
      8.8 x 10(5) cfu/g and that of coliform was 3.2 x 10(2) +/- 3.8 x 10(2) m.o./g.
      Poultry products on the other hand had a mean aerobic count of 6.8 x 10(5) +/-
      1.6 x 10(6), a mean mold and yeast count of 3.5 x 10(5) +/- 7.4 x 10(5) cfu/g and
      a mean coliform count of 6.4 x 10(2) +/- 5.2 x 10(2) m.o./g. Fecal coliforms were
      detected only in 60.0% of meat product samples and in 45.0% of poultry product
      samples. On the other hand Staph aureus was detected only in 10.0% of poultry
      product samples. Difference between the 5 types of vegetables was statistically
      significant (P = 0.00, and 0.02, respectively) for total plate and mold and
      yeasts counts. Among the 113 interviewed women, 80 used frozen food products.
      Twenty six of them (32.5%) had scores < 50%, those were classified as being bad
      as they were handling frozen food improperly which would contribute to outbreaks
      of food borne diseases. Less than 4% of the users used satisfactory practice
      during handling frozen foods. Illiteracy affected significantly the level of
      practice.

PMID- 17216976
TI  - Quality monitoring of composting processes of wastewater sludge in Alexandria.
AB  - There are two wastewater primary treatment plants in Alexandria (west and east).
      The produced primary sludge is mechanically dewatered and transported to sludge
      disposal site 9N where composting is carried out. However, prior to 1970,
      composting played a very minor role in sludge or solid wastes treatment because
      of greatly unfavorable balance between its economics and those of the principal
      competing option, namely landfill disposal. This study aims at monitoring and
      evaluating the composting process of demitted sludge produced from Alexandria
      wastewater treatment plants. Ten batches of sludge were composted. During the
      composting process the batches were been investigated and followed up to 3
      months. Representative samples (10 for each batch) were taken from these batches
      at the start of windrowing and after each turning (4-15 days) and were analyzed
      for physical; chemical; bacteriological; and parasitological characteristics,
      heavy metals, and plant nutrients. Results revealed that C/N ratio of the final
      compost product comply with the decree of the Minister of Agriculture No. 100
      11967, while moisture, C%, and TKN did not. Heavy metals, faecal coliforms, and
      helminthes complied with the decree No. 222/2002 for the Minister of Housing,
      Utilities, and Urban Communities. Moisture had positive correlation with both C
      and VS and negative correlation with pH. Temperature had negative correlation
      with TKN. Both total and faecal coliforms had negative correlation with
      temperature and positive correlation with C, N, and VS. It is recommended to
      optimize the quality of the produced sludge compost by use bulking agent rich in
      carbon and nitrogen as Hay or Rice straw, instead of the matured sludge compost.

PMID- 17216977
TI  - Current status of S. mansoni infection in El-Prince village, Alexandria
      Governorate.
AB  - The present work was implemented to determine the current status of Schistosoma
      mansoni infection in "El-Prince" village, near Alexandria, which was studied
      before as a control village between 1985 and 1990. Stool examination was
      performed on 571 of the inhabitants by Kato thick smear technique and intensity
      of infection was determined. Prevalence was found to be 15.4% with a percentage
      decrease of 53% from the 1990 survey. The geometric mean egg count (GMEC) ranged
      from 19.05 eggs/gram of stools in children aged five years or less to 81.86 in
      the oldest group greater than 50 years of age and averaged 42.26. Age stratified
      prevalence of infection peaked at 31.4% in the (20 to 25)-year-old age group.
      High prevalence of 23.6% was also observed in the age group from 36 to 50 years.
      Infection in males was higher than females (17.8% vs.13.5%). However the
      difference was not statistically significant (chi2 = 2.2, P = 0.0086). Risk
      factors significantly associated with the infection were an age more than 5
      years, male gender, males with water contact activities and having done a
      previous laboratory analysis for schistosomiasis. The community category of the
      village changed from high prevalence in 1990 to moderate prevalence in 2002. Most
      of the infected individuals (85%) had light intensity of infection (less than 99
      eggs /g stools). Active screening and treatment programs should be maintained in
      the area. More control measures should be directed towards older people who
      should be included in evaluation of control programs.

PMID- 17216978
TI  - Socioenvironmental predictors of abortion and stillbirths in an industrial
      community in Egypt.
AB  - Air pollution is considered to be one of the overgrowing problems of cosmopolitan
      distribution, due to marked progress in industrialization. The applied
      epidemiological and environmental studies related to reproductive health in the
      community, are considered as the main principles for comprehensive health
      development in industrial cities. The present study focused on the role of air
      pollution on the occurrence of abortion and stillbirths among married fertile
      women during the childbearing age (15-50 years) in two industrial areas, namely
      Helwan in Cairo Governorate and Tenth of Ramadan City in Sharqyia Governorate. A
      cross-sectional epidemiological study based on community background was
      implemented in the two studied areas. The unit of observation was the family
      including married fertile women based on specific inclusion criteria. Cluster
      sampling procedure was used in which the unit of sampling was the household,
      selected within a radius of not less than five Kilometers around the factories.
      Using Epi-info program, the total sample size in the two studied areas was 1934
      women. The interview questionnaire was the tool adopted for data collection,
      which includes gynecological and obstetric data related to reproductive health.
      The socio-economic status of studied women was determined using scoring system
      that includes the education and occupation of both couples. The environmental
      study was carried-out in the two areas in order to assess the levels of air
      pollutants and their chemical nature. Data management using Logistic regression
      analysis was done to determine the effect of independent variables, such as
      socioeconomic factor, exposure to air pollutants on the occurrence of abortion
      and stillbirths as examples of reproductive health problems. The mean age of the
      studied women was 33.8+/-8.8 years in Helwan and 28.1+/-6.5 years in Tenth of
      Ramadan. Also the study showed significant differences in both the socioeconomic
      status, smoking inside houses and parity between the studied women in Helwan and
      Tenth of Ramadan City. The overall prevalence of abortion and stillbirths among
      women in the studied areas were 29.2% and 4.5%, respectively. However, the
      prevalence of such reproductive health hazards among women in Helwan was
      significantly higher than in Tenth of Ramadan City. Also the results of
      environmental study indicated that Helwan has higher mean values of total dust
      count, suspended and respirable dust concentrations as well as lead concentration
      in the ambient air than in Tenth of Ramadan City. The Logistic regression
      analysis showed that the respirable dust concentration in the air and smoking
      inside houses are the significant independent factors for the occurrence of
      abortion. Moreover, Lead concentration in the air and women education is the main
      predictors of both abortion and stillbirths. Accordingly, the Egyptian
      authorities should attempt to improve air quality in urban industrial communities
      to promote reproductive health and prevent woman' s health hazards.

PMID- 17216979
TI  - The effect of cider vinegar on some nutritional and physiological parameters in
      mice.
AB  - The present work was designed to investigate health effects of cider vinegar
      using mice as experimental model. Groups of female ICR (CD-1) mice were treated
      with daily oral doses of 0.17, 0.51 and 1.02 ml of the vinegar/kg body weight for
      4 weeks. Cider vinegar induced a significant reduction in weight gain in animals
      treated with 0.51 ml/kg while others showed no significant differences in weight
      gain. The mean dry matter intake increased in animals treated with the smallest
      dose and significantly decreased in others. Hemoglobin (Hb), total erythrocyte
      counts (TEC) and total leukocyte counts (TLC) were raised in all treated groups.
      The activity of liver aspartate amino transferase (AST) decreased in the group
      treated with the smallest dose while no significant variations were recorded in
      the other groups. No significant differences were recorded neither in the
      activity of hepatic alanin amino transferase (ALT) nor in hepatic acid
      phosphatase (ACP). Liver alkaline phosphatase (ALP) noticeably elevated only in
      animals treated with 0.51 ml of vinegar/kg body weight per day. Treated groups
      also showed statistically significant increases in both mean liver and spleen
      weight. Kidney weight did not show significant differences. High doses of cider
      vinegar induced histopathological alterations in liver, stomach and duodenum.
      Vacuolated hepatocytes, erosion of gastric mucosa, dilatation in gastric glands
      and duodenum villus blunting are the common observed lesions noticed in organs of
      high dose-treated animals.

PMID- 17216980
TI  - Assessment of inhalation technique in children with asthma, Abha, Saudi Arabia.
AB  - The inhalation technique of asthma in children was assessed using the criteria
      defined by the standardized inhaler checklist of the Netherlands Asthma
      Foundation and Dutch asthma foundation. Four hundred and thirty seven newly
      referred patients to chest clinic, department of pediatric, Assir Central
      Hospital, Southwestern Saudi Arabia were instructed to demonstrate their
      inhalation technique and to fill out a questionnaire related to the inhalation
      instructions received before their referral. RESULTS: Four hundred and thirty
      seven patients newly referred for evaluation of their asthma (5-12 years of age
      with mean age of 7.16+1.69 years, 202 (46.2%) girls, 235 (53.8%) boys were
      included in the study. Two hundred two (46.2%) patients use MDI. The remaining
      (53.8%) patients use the DPI, 123 (52.35%) of them use turbohalers while 112
      (47.65%) use diskhalers. Only 36 patients (8.2 %) completed the assessment
      without making any mistake. Of the remainders, 399 (91.8%) made one or more
      mistakes. Of the MDI users, eleven patients (5.4%) performed correctly all the
      steps, and 54 (26.7%) performed correctly four or more steps. Ten (8.9%) of the
      diskhaler users performed all the steps correctly and forty nine (43.8) performed
      correctly four or more steps. Fifteen (12 2%) of the turbohaler users performed
      correctly all the steps and ninety five (77.2%) performed correctly four or more
      steps. One hundred five of the male patients (44.7%), performed correctly more
      than three steps as compared to 93 of the female patients (46.5) with p
      value=0.704. One hundred and one patients (67.3%) between the age of 8-12 years
      performed more than three steps correctly as compared to 97 (33.8%) of patients
      aged 5-7 years (p=0.001). CONCLUSION: In conclusion, many asthmatic children use
      their inhaler devices too poorly with the result of an unreliable drug delivery.
      Turbohaler device inhalation technique was the easiest, followed by diskhaler
      then lastly the MDI. Education of asthmatic children and their families is highly
      needed to make sure the patient perform the correct inhalation technique.

PMID- 17216981
TI  - Influence of free radicals on cardiovascular risk due to occupational exposure to
      mercury.
AB  - This study was designed to investigate the relation between occupational exposure
      to mercury and cardiovascular risk, as well as free radicals. The study subjects
      included 30 male workers exposed to mercury from a fluorescent lamp plant in
      Alexandria after exclusion of 12 workers with conditions that may bias the
      results. A matched control group of 20 male subjects were selected from a food
      industrial plant. The participants were subjected to interview, clinical
      examination, electrocardiography and R-R deep breathing variability test as a
      measure of cardiac autonomic function. Spot urine and venous blood samples were
      collected to measure mercury levels. Free radicals related markers were measured
      in serum namely lipid peroxide, superoxide dismutase (SOD) activity, catalase
      activity and glutathione S-transferase. Results showed significant longer
      electrocardiographic Q-Tc interval, which is corrected to heart rate, in exposed
      workers than in controls (p=0.002). The R-R deep breathing variability indices
      were significantly increased among exposed workers in comparison to controls
      (maximal variation (MV) ratio, p=0.024 & MV rate, p=0.019). The mercury levels in
      both urine and blood of exposed workers were significantly higher than controls
      (p<0.0001), with mean levels exceeding the permissible limits. Free radicals
      related markers revealed significant higher level of lipid peroxide, as well as
      significant lower levels of SOD activity, catalase activity and glutathione S
      transferase among exposed workers than among controls (p<0.0001 for all).
      Independent relations were observed between Q-Tc and lipid peroxide, and between
      MV rate and SOD and catalase activities among exposed workers after adjustment
      for the confounders by multivariate regression analyses. These findings may
      suspect a cardiac autonomic dysfunction probably related to free radicals in
      mercury exposed workers. Also, it may through light on some preventive
      implications.

PMID- 17216982
TI  - Epidemiological correlates of hysterectomy, a hospital based study 1995 -1996 at
      Ain Shams Maternity Hospital.
AB  - Hysterectomy is one of the most frequently performed major surgical procedures
      for women. Study the epidemiological correlates of hysterectomy and identify the
      different indications that lead to the operation as well as determine its
      frequency. SUBJECTS AND METHODS: A retrospective study was performed which
      included 231 women who had undergone hysterectomy during 1995-1996. Data about
      the various characteristics of women, indication, and type of surgery were
      retrieved from the medical fles of women in Ain Shams Maternity Hospital.
      RESULTS: The hospital incidence rate of hysterectomy during 1995-1996 was
      9.8/1000 admission, while it rose to 13.8/1000 in the year 2000 (recent data from
      hospital statistics unit) Epidemiological data showed that the mean age of women
      was 45.4+/-8.9, the highest frequency of hysterectomy was in the age group 45-54
      years (41.2%). Hysterectomy in those aged less than 35 years was 7.3%. Previous
      abortion accounted for 48.5% early age at menarche (< or =12) was 13%,
      multiparity (> or =5) was 54.4%. Among women aged less than 35 years, uterine
      leiomyoma was the commonest indication (29.4%), while dysfunctional uterine
      bleeding was the commonest indication among those aged 35-<45, and 45-<55 and
      accounted for 40.6% and 60% respectively. Those aged > or =55 years, uterine
      prolapse was the commonest indication (53.6%). Malignant neoplasm covered less
      than 5% of all hysterectomies. Among nullipara, uterine leiomyoma was the most
      frequent indication (66.7%), while among parous women, dysfunctional uterine
      bleeding was the most frequent (56%). The most common obstetric indication
      leading to hysterectomy was uncontrolled postpartum hemorrhage and ruptured
      uterus (57.2%) of all obstetric causes. The abdominal route was the commonest
      approach for hysterectomy (54.1%), followed by the vaginal (35.9%). CONCLUSION
      AND RECOMMENDATIONS: Hysterectomy rate in Ain Shams Maternity hospital showed a
      significant increase by the year 2000 than during the period of the study.
      Further studies are needed to identify the reasons for such increase and to
      reduce unnecessary operations. The present study draws the attention of the
      importance of prenatal care for early detection of high risk women, and prevent
      complications of bleeding specially in women under 35 years who may not have
      completed their families and who may prefer other alternatives to surgery.

PMID- 17216983
TI  - Psychometric study of dysthymic patients and their first-degree relatives.
AB  - Psychometric evaluation of severity of depression and personality characteristics
      of 20 dysthymic patients (mean age 29.05+/-7.08 ys.) was carried out using
      Hamilton Depression Rating Scale (HDRS) and Eysenck Personality Questionnaire
      (EPQ) and was compared with that of 20 major depressive patients (mean age
      33.60+/-7.7ys.) and 20 normal controls (mean age 32.85+/-6.17 ys.). Psychosocial
      stressors that might trigger depression were also looked for. All first-degree
      relatives (118 persons) were subjected to clinical interview for detection of
      dysthymia. EPQ was also applied to assess their personality characteristics.
      Depression among dysthymic patients was mainly of mild degree. Severe depression
      was found in about 55% of major depressive and none of dysthymic patients.
      Application of EPQ revealed high neuroticism among dysthymics and high
      psychoticism among major depressives. Lie scale was high for both groups.
      Psychosocial stressors were more reported by dysthymic patients; however they
      were of mild or moderate degrees. Stressors reported by major depressive patients
      were mainly acute and severe. Assessment of the first-degree relatives revealed
      that 66% of dysthymics' relatives had dysthymia or high EPQ scores compared to
      36% of major depressives and 22% of normals.

PMID- 17216984
TI  - Reassessment of some environmental conditions of Maawa el-Sayadeen squatter area.
AB  - Reassessment of some environmental conditions of Maawa El-Sayadeen squatter area
      was carried out during 2000. Due to unplanned urbanization, environmental
      sanitation has been ignored for several decades resulting in many health, social
      and economic problems. Maawa El-Sayadeen was chosen by West District officials
      for environmental and health upgrading in 1995, which depended mainly upon health
      education in addition to some engineering constructions. The environmental
      conditions and health status were reporded before 1995 and after 2000. The
      reassessment proved that, there was an increase in number of families use tap
      water inside the house by 29% compared with 1995 assessment. Moreover, number of
      families using water closets increased by 15%, also wastewater disposal throught
      public sewers increased by 34%. However, a decrease by 17% in dry areas
      surrounding the houses was recorded. Solid waste storage improved by 11% although
      solid waste collection sites decreased by 23%. It is concluded that, after Maawa
      El-Sayadeen area was exposed to a certain level of environmental upgrading, the
      environmental conditions of the area were some how better categorized, however,
      further training programs should be taken into account or stressed including
      increase of people awareness, and strong partnership should be developed with
      their non governmental organizations.

PMID- 17216985
TI  - Environmental factors and health problems among workers of the national project
      in Toshka.
AB  - The National Project in Toshka is a recognized agricultural one, as well as a
      comprehensive developmental project. The present study was carried out to
      investigate environmental factors and health problems among workers in this
      National Project. Environmental levels of vibration, noise, heat stress, total
      suspended particulates and respirable dust were measured in the different
      activities of the project during May 2000. The health records of Behera Company
      Incorporation, the project main implementing contractor, in the period 1997-1999
      were analyzed. Workers were classified according to the nature of occupational
      exposure into three groups namely; earth workers, concrete workers, and services
      and administration workers. Records of occupational accidents of the same group
      of workers and in the same period were analyzed as well. Results showed that all
      the measured environmental factors were within the permissible levels of exposure
      in the different project activities. Workers showed a significant lower rate of
      total health problems in the last studied year (1999) as compared to the previous
      two years (1997-1998) (p=0.001). Prevalence rates of musculoskeletal disorders,
      urinary tract troubles, ear-nose-throat (ENT) problems and chest problems were
      significantly higher in earth and concrete workers than in services and
      administration workers (p=0.001, 0.011, 0.036 and 0.044, respectively). Both
      occupational accident frequency and severity rates were very low in comparison to
      other major construction projects such as the High Dam. These rates showed
      decreasing trends throughout the studied years; however, relatively higher rates
      were observed among earth workers than the other groups. Miscellaneous wounds
      were the commonest presentation of occupational injuries among the three
      occupational groups. In conclusion, the current use of modern technology
      accounted for the low levels of enviro mental exposure factors, as well as the
      high safety standards. Workers showed a significant degree of acclimatization to
      work in this region; therefore, inhabitants and workers should be encouraged to
      engage this new community. The low rates of health problems among workers
      observed in this study reflected a satisfactory level of medical services.
      Preplacement and periodic medical examinations of construction workers aught to
      consider musculoskeletal, urinary tract, ENT and chest conditions among them.

PMID- 17216986
TI  - Assessment of drinking water quality of Borg el-Arab water purification plant.
AB  - Borg El-Arab drinking water purification plant takes its raw water from El
      Noubaria Canal at the kilometer 95. EI-Noubaria canal gets its water from the
      Nile at two points. The main bulk of water comes from El-Riah El-Behiery, while
      the second source of water coming from El-Riah El-Nassery. There are four
      agricultural drains at the kilometer 53.0, 66.0, 71.9 and 85.4 which return back
      to the canal and represent the sources of pollution of the canal. Chemical,
      physical and trace elements analysis were carried out for raw and treated water
      of Borg El-Arab drinking water purification plant. It was found that the quality
      of treated water for the different parameter, are in agreement with the Ministry
      of Health Decree No 108/1995 for drinking water. Regarding total dissolved solids
      level, the quality of water was fair during Autumn and Summer as its value was
      876.7 mg/l and 701.2 mg/l respectively, it was poor during spring as it reached
      1113 mg/l, while during winter it was unacceptable (1312.7 mg/l) which exceed the
      higher permissible limit of the Ministry of Health Decree No 108/1995. This high
      TDS values make objectionable tastes in the public water supplied to Borg El-Arab
      city and the North West coast summer resorts. This taste of water provides no
      assurance to the public that such water is free of pathogens or toxic inorganic
      chemicals. So, we recommend El-Hager canal as new intake source for providing
      Borg El-Arab drinking water purification plant with raw water free from
      pollutants and low in total dissolved solids concentration.

PMID- 17216987
TI  - Accidental poisoning with household detergents.
AB  - Caustic substances and home detergent poisoning remain a threat to the health of
      young children. The aim of the present work was to estimate the occurrence of
      household poisoning due to detergents and to study some demographic and
      behavioral correlates. MATERIAL AND METHODS: Through systematic random sampling
      technique one tenth of all women attending pediatric and family medicine clinics
      in King Khalid University Hospital over two months were selected and interviewed
      to complete questionnaire. They were asked about history of poisoning due to
      detergents in their family in addition to their demographic-and practice
      regarding storage, use and disposal of detergents. RESULTS: The sample amounted
      to 318 mothers with mean age 34.2+/-7 13 years. 55(17 3%) reported history of
      poisoning due to detergents in their families Housewife mothers mothers with ?5
      children, not reading detergents' labels, using detergents' containers for food
      and mixing different detergents; all were significantly associated (P<0.05) with
      higher rates of detergents poisoning in families (24.6%, 25.3%, 30.6%, 35.7% and
      50%, respectively). RECOMMENDATIONS: health education programs concentrating with
      storage, use and hazards of detergents are recommended for mothers.

PMID- 17216988
TI  - Behavioral risk factors among physicians working at Faculty of Medicine - Ain
      Shams University.
AB  - BACKGROUND: Behavioral factors and lifestyle are increasingly recognized as
      underlying causes of preventable morbidity and premature death. Physicians
      frequently advise their patients about quitting smoking, losing weight, and
      increasing physical activity; so what about their own personal behavioral
      choices? PURPOSE: To determine the prevalence of behavioral risk factors that
      physicians are currently practicing and its relation to some demographic
      variables. METHODS: 616 staff physicians, of both sexes, were randomly selected
      to fill a questionnaire inquiring about major behavioral risks. Among the
      behavioral risks investigated were smoking, physical inactivity, overweight, non
      use of seatbelts. Univariate and multivariate analysis were done in which all
      behavioral risks were dichotomized into at risk or no risk and related to
      different demographic factors. RESULTS: 382 physicians participated (response
      rate 62%). Current smoking among male physicians was 26.6%, past smokers 12.1%,
      51% of current smokers reported smoking in front of patients or in clinic. Among
      all participants, 84% were sedentary (no, or irregular physical activity), 59.9%
      were overweight (Body Mass Index > or = 25). Regular use of seatbelts was only
      followed by 11.2%. Routine checkup within the past year was reported by 18.6%,
      blood cholesterol checkup by 15.4%. Regarding aspects of women's health, a
      clinical breast examination was done in 32.5% of women physicians > or = 40
      years, a cervical smear in 10%, and a mammogram in 7.5%. Different behavioral
      risks were found to be associated with different sets of demographic variables.
      CONCLUSION: Efforts are necessary to promote physicians to quit smoking, increase
      physical activity, lose weight, use seatbelts, screen for chronic diseases, to
      minimize preventable disorders.

PMID- 17216989
TI  - Ultra sonographic measurements of the normal liver and spleen among Egyptians 10
      50 years old.
AB  - OBJECTIVE: To determine reference values of ultra sonographic (US) measurements
      of the normal liver, spleen, portal vein, right and left periportal thickness,
      gall bladder wall thickness and common bile duct diameter of Egyptians. DESIGN:
      Community-based cross sectional study. SETTING: Kalama village in Nile Delta, 40
      kilometers north of Cairo. SUBJECTS: 10% systematic sample of people above 10
      years of age. Selection criteria included normal clinical examination, normal
      liver functions by ALT, absence of hepatitis B and C virus markers and liver or
      spleen pathology by US. MEASUREMENTS: Organometery of the liver, spleen, portal
      vein, right and left periportal thickness, gall bladder wall thickness and common
      bile duct diameter by US. RESULTS: 217 subjects were admitted to the study out of
      700 examined. All measured parameters increased with age till 20 years. There was
      no significant difference in measurements between males and females. The means,
      standard deviation and 95th percentiles of all measurements were higher than
      those recorded in other studies. CONCLUSION: Egyptian norms for US organometery
      of the liver, spleen, portal vein and gall bladder are different from those of
      other countries. We suggest that Egyptian sonologists use these norms in routine
      practice.

PMID- 17216990
TI  - Saudi Arabia experience trial of fluvastatin (Lescol) in the treatment of
      hyperlipidemia.
AB  - This study was carried out to assess the efficacy, safety and tolerability of
      fluvastatin as monotherapy in the treatment of primary hypercholesterolemia. This
      multicenter study started with 467 patients but only 315 subjects completed 12
      weeks treatment. Patients followed a standard lipid-lowering diet for 3 weeks
      before entering and throughout the study. Every patient received fluvastatin 20
      mg once daily with the evening meal for the first 6 weeks, from week 7 to week 12
      the daily dose was changed to one capsule 40 mg daily in the evening. Results
      showed that the mean percent changes in lipid parameters between baseline and
      endpoint was as follows: LDL-C (-32.7%); total cholesterol (-29.42%),
      triglycerides (-19.7%) and HDL-C (16.6%). Meanwhile, the mean percent increase in
      liver enzymes between baseline and endpoint was 17.2% for ASAT and 20.3% for
      ALAT, respectively, but the mean values of both enzymes at the endpoint were
      within normal range. The most frequent side effects being gastrointestinal (4.3%)
      including dyspepsia, nausea, flatulence and diarrhea. In conclusion, fluvastatin
      as monotherapy in the treatment of hypercholesterolemia among Saudis was found to
      be safe, well tolerated and produced a significant improvement in the overall
      lipid parameters.

PMID- 17216991
TI  - Glutamine study in hepatic schistosomiasis and effect of conventional medical
      therapy.
AB  - The liver plays a major role in urea and glutamine metabolism where it maintains
      ammonia and bicarbonate homeostasis under physiological and pathological
      conditions. Glutamine assessment in different liver diseases showed deviations
      from normal serum values. In the present study, glutamine level in serum [serum
      glutamate values] (SGV) and liver tissue homogenates (liver homogenate glutamine
      values] (LHGV) in patients with schistosomal hepatic fibrosis with and without
      conventional supportive medical therapy and anti-schistosomal therapy were
      correlated. LHGV in liver tissue homogenates from cases were higher than those of
      matched controls. SGV of patients with late hepatic schistosomiasis were greater
      than those with early stages of the disease. All patients, whether in early or
      late schistosomal hepatic fibrosis, showed reduction of SGV after treatment. We
      came to the conclusion that in patients with schistosomal hepatic fibrosis,
      whether early or late, there is a derangement of glutamine metabolism which could
      be corrected partially by the conventional supportive medical therapy. Again,
      estimation of glutamine in serum could be considered an early and reliable
      parameter for the assessment of liver function in patients with schistosomal
      hepatic fibrosis.

PMID- 17216992
TI  - Down syndrome and maternal age: changes over time and review of risk factors.
AB  - During 1987-1996, 292 Egyptian Down syndrome (Trisomy 21) infants were identified
      in Human Genetics Department in Alexandria. They comprised 139 males and 153
      females (sex ratio 0.91). Data on maternal age, paternal age and birth order were
      analyzed. Maternal ages were examined for transient changes over time and for
      linear trends. Significant changes in maternal age over the 10 years period of
      study were observed. First born infants were at greater risk of trisomy 21 than
      higher order of births, independent of maternal age.

PMID- 17216993
TI  - Utilization of maternal health services offered by the Health Insurance
      Organization in Alexandria.
AB  - This study examines the extent of utilization of maternal health services (MHS)
      currently offered by Health Insurance Organization (HIO) in Alexandria. A total
      of 1040 insured married females working in primary, preparatory and secondary
      schools in three educational regions in Alexandria were interviewed. Data was
      collected about socio-economic status of females, their knowledge about MHS
      offered by HIO, as well as sources of receiving MHS other than HIO. Barriers
      preventing utilization of such services and recommendations for improvement were
      explored from beneficiaries. The results revealed that for the last pregnancy,
      about half the sample utilized antenatal services and about one fourth utilized
      natal services, while a very small percentage (8%) utilized family planning
      services. The private sector was the main source for receiving MHS for non
      utilizer. Lack of confidence and low quality of services were the main barriers
      preventing utilization. Complete physical examination, examination of fetal heart
      sound and improvement of physical environment of obstetrics and gynecology
      department were the main recommendations for improvement of MHS offered by HIO.

PMID- 17216994
TI  - Immunological properties of cellular and whole-culture leptospiral bacterins.
AB  - Two bivalent leptospiral bacterins were compared for safety in guinea pigs and
      for potency in hamsters. One bacterin (Bacterin A) was prepared from the cellular
      material of Leptospiral icterohaemorrhagiae and Leptospira canicola cultures
      propagated in Stuart's modified medium with 7% rabbit serum. The 2nd bacterin
      (Bacterin B) contained whole leptospiral cultures grown in synthetic medium.
      Neither bacterin induced adverse local or systemic reactions when injected
      intraperitoneally (I/P) in guinea pigs. In hamsters, 1/400 and 1/800 of the
      recommended dose of bacterin B for cattle protected 100% of the vaccinated
      hamsters against challenge exposure of either virulent leptospiral serotype. A
      dose representing 1/400 of the recommended dose of bacterin A for cattle
      protected 80% of vaccinated hamsters against challenge exposure to L.
      icterohaemorrhagiae and 90% against challenge exposure to L. canicola, whereas
      the 1/800 dose level protected only 10% of the vaccinated hamsters challenge
      exposed to virulent culture of L. icterohaemorrhagiae or canicola. The
      possibility was demonstrated that at least one soluble antigen of strong
      immunogenic properties is produced in cultures of L. icterohaemorrhagiae and L.
      canicola.

PMID- 17216995
TI  - Immunological assay after vaccination of goats with Brucella melitensis Rev. I
      and Brucella abortus 45/20 vaccines at Saudi Arabia.
AB  - The living smooth Brucella melitensis Rev. I vaccine given in the normal dose
      (7x10(8) organism) to goats 3 to 5 months of age stimulated a marked increase in
      agglutinin titer. Fractionation of pools of serum by gel filtration by anion
      exchange chromatography, using diethylaminoethyl (DEAE -) cellulose showed that
      both IgM and IgG agglutinins were present from 12 to 47 days after goats were
      vaccinated. Only mercaptoethanol (ME)-sensitive agglutinins were detected in most
      goats 4 months after vaccination, but 2 of 30 goats retained ME-resistant
      agglutinins for the 13 1/2 - month observation period. Fractionation of serums
      from goats representative of these 2 types of serologic response indicated that
      most goats had only IgM agglutinins, whereas the 2 given goats had activity in
      the IgG fraction. Adult goats given Brucella abortus 42/20 adjuvant vaccine and
      revaccinated 5 months later developed low agglutination titers to smooth antigen,
      and all became test positive to the antiglobulin test. Fractionation of serum of
      pools taken 1 week and 8 months after revaccination indicated that antibody
      activity was restricted to the IgG fraction. Sera from 5 vaccinated and
      nonvaccinated goats which were positive by bacteriological culture examination at
      necropsy 31 to 47 days after goats were given conjunctival inoculation of
      virulent B. melitensis had antibody activity in both IgG and IgM fractions. Test
      positive reaction to the ME, complement-fixation (CF), and antiglobulin (AG) test
      were restricted to the IgG-containing fractions of serum, whereas reactions to
      the agglutination (STT) and the card tests appeared with either or both
      fractions. The effect of these findings on the choice of tests for the
      differentiation of vaccination response is discussed.

PMID- 17216996
TI  - A prospective study: prediction of the first variceal haemorrhage in schistosomal
      and non schistosomal liver disease.
AB  - A prospective study was conducted on liver disease patients without previous
      history of bleeding (haematemesis and/or melena) to identify those at highest
      risk of bleeding. A hundred and twenty non-alcoholic patients (96 males and 24
      females), ages ranging from 30 to 60 years were studied. Patients were followed
      for up to two years or to time of bleeding (mean 18 +/- 7.3 months), during which
      34 (28.3%) patients bled. Schistosomal patients showed less incidence of bleeding
      (12.1%, p < 0.05) than those with mixed aetiology (Schistosoma and cirrhosis
      23.5%, and chronic active hepatitis and schistosoma 44.4%). The presence of
      positive viral markers (either HCV antibodies or HBsAg) was associated with a
      higher percent of bleeding during the follow-up period (43.2% and 45.4%,
      respectively), than those negative for these markers (21.7%, 24.4%,
      respectively). Univariate analysis showed the following significant risk factors
      associated with bleeding: modified child classification, reduced platelet count,
      endoscopic findings of cherry red spots, gastric varices and increased grade of
      oesophageal varices. Multivariate analysis revealed that the risk of bleeding was
      significantly related to the presence of cherry red spots, the presence of
      gastric varices, grade of oesophageal varices and the patient's prothrombin time.
      In conclusion, bleeding from oesophageal varices is a frequent and serious event
      in patients with chronic liver disease. The risk of variceal bleeding from liver
      disease with mixed aetiology (schistosomiasis associated with viral hepatitis HBV
      or HCV) was found to be significantly higher than that with schistosomal
      aetiology alone. The endoscopic findings of cherry red spots, gastric varices,
      increased grade of oesophageal varices and to a lesser extent the prothrombin
      time were found to be high risk factors. Patients having those risk factors
      should be considered for prophylactic measures.

PMID- 17216997
TI  - Ultraviolet, chlorine and ozone disinfection of some enteroviruses in drinking
      water and treated effluents.
AB  - The inactivation efficiency of chlorine, ultraviolet light and ozone were
      determined for poliovirus type 3, Coxsackievirus type B4 and Hepatitis A virus in
      drinking water and treated effluent. Ultraviolet was more efficient than the
      other two disinfectants at wave length 254 nm where no infective virus was
      detected after 4 min of UV irradiation in both drinking water and treated
      effluent. Inactivation by chlorine dose more than 25 mg/L was sufficient for
      studied viruses in both drinking water and treated effluent. Also virus-seeded
      drinking water was exposed to ozone for 18 min at ozone rate of 319 mg/L/h to
      obtain the maximum inactivation of PV3, CoxB4 and HAV but about 20 min of ozone
      exposure was needed for treated effluent. Physico-chemical parameters were
      measured before and after disinfection assay. No significant changes were
      observed.

PMID- 17216998
TI  - The value of the tuberculin skin test in patients with tuberculous meningitis.
AB  - To determine the clinical utility of the tuberculin purified protein derivative
      (PPD) skin test in patients suspected of having tuberculous meningitis (TBM), the
      test was applied on admission to 180 patients suspected of having tuberculous
      meningitis and to 50 patients with proven bacterial meningitis admitted to the
      Abbassia Fever Hospital, Cairo, Egypt, during the period 1987 to 1989. Admission
      tuberculin positivity in evaluated groups revealed the following: overall suspect
      TBM cases--17% (31/180), culture-confirmed TBM cases--19% (16/83), and culture
      confirmed acute bacterial meningitis cases--14% (7/50). Repeat PPD skin test at
      60 days in surviving presumptive/confirmed TBM cases revealed a significant
      increase in tuberculin positivity to 62% (58/93) from admission (p < 0.001).
      Evaluation of PPD positivity by clinical stage of TBM revealed 36% positivity in
      alert patients as compared to 12% positivity in comatose patients (p = 0.01).
      Admission tuberculin skin testing as a diagnostic aid for clinical management of
      tuberculous meningitis is of limited utility in our study population because of
      the high prevalence of tuberculin positivity in the Egyptian population
      (potential false positive correlation with the acute presentation) and the
      advanced stage of TBM at presentation to Egyptian public hospitals (potential
      false negative correlation).

PMID- 17216999
TI  - Early detection of nephrotoxic effects due to low-dose exposure of cadmium among
      cigarette smokers.
AB  - The effects of low-level exposure to cadmium due to cigarette smoking on renal
      function were judged by the estimation of urinary levels of total proteins,
      cadmium, alpha-1-microglobulin (alpha1M) and glutathione S-transferase (GST)
      activity among 50 males (38 smokers and 12 control non-smokers). Elevated urinary
      cadmium levels [2.408-28.160; 9.31 +/- 7 .1 microg Cd/gm urine creatinine] were
      observed among the majority of smokers (24 cases, 63.16%) and these levels showed
      a positive correlation with age and smoking index. Furthermore, urine total
      proteins [115.18-652.14; 242.89 +/- 121.88 mg protein/gm urine creatinine) were
      increased suggesting glomerular involvement among 20 cases (52.63%) of smokers.
      In addition, urinary alpha1M levels (14.645-86.053; 34.05 +/- 16.83 mg alpha1M/gm
      urine creatinine) and urinary GST activity [0.0-0.008; 0.00015 +/- 0.0002
      micromol/min/100 microl/gm urine creatinine] were elevated among 18 (47.37%) and
      20 (52.63%) cases of smokers respectively. Since urinary alpha1M and GST
      originate from renal proximal tubules, the data of the present investigation
      could reflect early low-level cadmium exposure nephrotoxic effect on both the
      glomeruli and tubules.

PMID- 17217000
TI  - A study of nosocomial infection in a general hospital.
AB  - The present study was conducted in Hail General Hospital, in Kingdom of Saudi
      Arabia, over six months period starting from December 1994. All notified cases of
      nosocomial infections were taken into consideration. Cases who satisfied the
      definition and criteria of nosocomial infection were included in the study (n =
      105). Data were abstracted from the special routine monthly resorts to the
      General Directorate of Health Affairs. The results of the present study revealed
      that invasive procedures were conducted for the majority of cases (81.9%). The
      most common site of infection was urinary tract (36.6%), followed by respiratory
      and wound infection (23.8% and 22.8% respectively), while other sites accounted
      for the remaining part of the sample (16.8%). Out of the culture positive cases
      (n = 101) gram negative bacteria represented 85.15% of cases where the most
      common ones were Klebsiella pneumonia and pseudomonas. Bivariate analysis
      revealed a significant linear association between invasive procedures and age
      (Mantel Hanszel test = 17.37). Moreover, invasive procedures were found to be
      significantly related to the occurrence of gram negative infection (chi2 = 4.77).
      Multiple regression analysis, for factors affecting length of hospital stay,
      showed that age and presence of host factors lowering host resistance had
      significant effect in prolonging the duration of stay among cases.

PMID- 17217001
TI  - Screening of some food poisoning bacteria in sausage and hamburger meat.
AB  - Microbial investigation of 30 samples of sausage meat and 30 samples of hamburger
      meat, freshly prepared, were collected randomly from different markets in
      Alexandria city, to determine the bacteriological status of these products. The
      average counts/gm of total bacteria, total coliforms and fecal coliform in
      sausage meat were 1.33 x 10(7), 9.16 x 10(5) and 1.11 x 10(3) respectively, and
      in hamburger samples were 8.47 x 10(5), 2.63 x 10(3) and 1.35 x 10(3)
      respectively. Shigella, Escherichia coli, Staphylococcus aureus and Proteus spp
      were isolated with various percentages, whereas Salmonella spp was isolated from
      sausage only. The public health importance of the isolated microorganisms are
      fully discussed.

PMID- 17217002
TI  - Chloramphenicol drug failure in typhoid fever.
AB  - Two hundred positive blood culture typhoid patients admitted to Embaba Fever
      Hospital, Giza province, were subjected to: 1) Careful history and thorough
      clinical examination. 2) Complete blood picture. 3) Widal agglutination test. 4)
      Urine and stool cultures for Salmonellae. 5) To the isolates of the cultures,
      disk diffusion chloramphenicol susceptibility test, minimum inhibitory
      concentrations and chloramphenicol acetyl transferase test were performed. The
      dose of chloramphenicol was restricted to 50 mg per Kg body weight daily,
      whatever the route used; whether oral, rectal or intravenous. When fever did not
      drop up to 5 days or the patient presented with typhoid complications or the
      blood culture revealed resistant Salmonellae, quinolones or third generation,
      cephalosporins were administered. Measurement of the level of chloramphenicol in
      the blood was performed for every patient. Fifty (25%) patients were found to be
      resistant in vitro and in vivo to chloramphenicol. All their Salmonellae isolates
      were resistant to chloramphenicol, the mean zone size was 10 mm, the mean
      inhibitory concentration was 64 microgram per ml. and all were positive for
      chloramphenicol acetyl transferase. There was no significant difference in the
      serum level of chloramphenicol between susceptible and resistant groups to the
      drug. Results were interpreted and discussed.

PMID- 17217003
TI  - Viral hepatitis C infection among Egyptians the magnitude of the problem:
      epidemiological and laboratory approach.
AB  - This study examines the relative importance of risk factors for viral hepatitis C
      infection and estimates the magnitude of HCV problem among Egyptians. It is a
      continuation of a recently performed cross-sectional study conducted on more than
      5000 Egyptians. Serum samples (1945) were analyzed for liver enzymes (SGPT and
      SGOT) to evaluate the status of liver affection. One hundred and sixty nine
      samples (103 confirmed HCV seropositives and 66 seronegative) were analyzed for
      PCR HCV RNA to estimate the frequency of HCV viraemia among those individuals.
      Rates for HCV seropositivity by ELISA test in mass screening were corrected using
      predictive value of a positive test at prevalence between 5-50%. Attributable
      risk and population attributable risk estimates were calculated for those
      significant factors in logistic regression analysis. Overall number of HCV
      infected individuals was estimated for age groups of 15-65 years and the numbers
      of HCV related liver complications were estimated. HCV PCR RNA was positive for
      50% of ELISA-seropositive samples and for 13.8% of the seronegative samples.
      However, only 5% of those individuals with HCV seropositivity and 3.7% of those
      with PCR RNA positivity Showed SGPT serum levels above 1.5 normal. The overall
      age, sex and urban/rural adjusted rate of true HCV seropositivity is estimated to
      be 15.6% among working Egyptians between 15-65 years. Attributable risk due to
      injections for the treatment of bilharziasis is estimated to be 47% (95% CL = 38%
      55%) among exposed males. Blood transfusion was estimated to be responsible for
      87% (95% CL = 57%-96%) of cases among previously transfused females. Population
      attributable risk for injections for treatment of bilharziasis among working
      urban and rural males is estimated to be 15% and 11% respectively. Blood
      transfusion and sharing contaminated needles contributed by 24% of cases (for
      each) among working urban females. Previous hospitalization contributed by 36% of
      cases among working rural females and by 10% among working urban males. As for
      the national estimate of cases of HCV seropositivity we estimated more than 5
      million individuals with an expected number of chronic hepatitis of varying
      degrees of 3.5 millions. HCV viraemia with high probability for transmission is
      present in more than 50% of those individuals and liver cirrhosis cases expected
      to develop within an average of 20 years of infection are in the range of 350-700
      thousand cases. The major proportions of population attributable risk are due to
      other undefined risk factors associated with age, male sex, living in rural areas
      and in lower and upper Egypt. Further research is needed to elucidate those
      factors prevailing in these areas, associated with increased risk of HCV
      infection.

PMID- 17217004
TI  - Study of the risk factors for viral hepatitis C infection among Egyptians
      applying for work abroad.
AB  - The aim of this study was to identify the risk factors for viral hepatitis C
      infection among Egyptians. A cross-sectional study with case-control analysis was
      conducted including 5071 Egyptians applying to the Ministry of Health
      Laboratories for certification of freedom from viral hepatitis (B and C) to work
      abroad. A questionnaire designed to cover the most important known and suspected
      risk factors was filled out by physicians interviewers before blood drawing and
      after proper orientation of the purpose of the study. The overall seropositivity
      among the whole sample for HCV was 31.5% and was significantly lower among
      females (13.2%) than among males (34%). A consistent increase of seropositivity
      for HCV antibodies with age (in males and females and in urban and rural areas)
      was observed with a peak level of 54.9% in all individuals for the age group 45
      49 years (significant trend p < 0.0001). A significant increase of seropositivity
      (p < 0.005) above 25 years of age (35.7%) than below this age 12.8%) was observed
      on examination of HCV distribution in 5-year age group. Married individuals have
      a significant higher seropositivity for HCV than non-married (38.2% and 20.9%
      respectively OR = 2.3, 95% CL 2.1-2.7). Individuals living in rural areas had
      significantly more HCV seropositivity than those living in urban areas (OR = 1.7,
      95% CL 1.5-2.0). Also, individuals living in Cairo and seashore governorates had
      significantly lower seropositivity (14.7% and 12.7% respectively) than those
      living in governorates in upper or lower Egypt (29.4% and 36.3% respectively).
      Medical procedures risk factors identified to be associated with significant
      higher HCV seropositivity included: past history of injections for bilharziasis,
      use of common syringes, dental extraction, injections for urography, blood
      transfusions and previous hospitalizations. Multivariate logistic analysis
      revealed that only age, male sex, marriage, rural residence, living in upper and
      lower Egypt, injections for bilharziasis and urography were significant in the
      final equation for the whole group. Blood transfusion was significant in the
      final regression analysis among females in urban living and hospitalization was
      significant among males in urban living and females in rural living. Further
      research is needed to elucidate those factors prevailing in rural areas and in
      upper and lower Egypt associated with increased risk for HCV infection.

PMID- 17217005
TI  - Prevalence of antibiotic resistance among Egyptian Salmonella typhi strains.
AB  - This report describes the resistance of 537 Salmonella typhi isolates identified
      in Egypt between 1990-1994. Results indicated a high isolation rate for multiple
      resistant S. typhi (> 71% of isolates collected in 1992-93), particularly to the
      three standard drug regimens of the clinically relevant antibiotics; ampicillin,
      chloramphenicol and trimethoprim-sulfamethoxazole. This adds to the complexity
      and difficulty of treating infections caused by these organisms. Resistance of S.
      typhi was associated with a transferable 120 MD plasmid. The organism was
      sensitive to amikacin, aztreonam, cephalothin, ceftriaxone, gentamicin and
      nalidixic acid, suggesting the use of aztreonam and ceftriaxone as alternative
      therapeutic drugs for the treatment of multidrug-resistant S. typhi. These
      results may provide a clinically useful evaluation of the spread and acquisition
      of resistance among S. typhi strains in Egypt.

PMID- 17217006
TI  - Assessment of nutritional status of pediatric cancer patients.
AB  - The study was done to identify which parameters are most useful to be used for
      nutrition assessment in pediatric cancer patients. The study included 70
      pediatric cancer patients (48 males and 22 females) age 4-10 years. Patients were
      classified into 3 groups based on type of cancer (Lymphoma, leukemia and
      rhabdomyosarcoma). The period of the study was divided into 3 stages according to
      treatment (initial, during and at the end of the 6 months period). The patients
      were subjected to nutrition assessment through using 24 hours dietary recall and
      anthropometric measurements. Also the relationship between nutrient intake and
      socioeconomic status of the patients was studied. The results showed positive
      between each of triceps skinfold (TSF), arm circumference (AC), arm muscle
      circumference (AMC), height (Ht) and weight categories (as a percent of ideal
      body weight). These parameters can be used to assess nutritional status of
      pediatric cancer patients throughout the stages of treatment. The results of the
      24 hours dietary recall showed a decrease in protein and caloric intake of all
      the patients by the end of the 6 months period. All the patients had low intake
      of vitamins A and C and calcium. A positive correlation was found between the
      intake of these 3 nutrients and socioeconomic level of the patients.

PMID- 17217007
TI  - The ecological characteristics of Anopheles mosquitoes associated with low
      malaria transmission in Siwa oasis, Egypt.
AB  - The ecology of Anopheles sergentii and An. multicolor was investigated over eight
      months to examine the entomological factors maintaining the low Plasmodium vivax
      transmission in Siwa oasis. The two species were encountered as larvae while the
      dominant species, Anopheles sergentii was also collected as adults. Breeding
      sites were characterized for the two species in six localities. Larvae of both
      species were common during June and November. In Bahi El Din as an indicator
      village with a higher endemicity, An. sergentii females were endophilic but more
      common inside animal sheds than in houses, attracted more to donkey-baited traps
      than to human hosts, more endophagic as human biters and were more common in
      May/June and November. Female survivorship was higher in November than in the
      other months. Vector potential of An. sergentii was predicted and revealed that
      the species characteristics (low human contact, short survival and zoophilic
      feeding behavior) are responsible for maintaining such low and unstable malaria
      in Siwa oasis.

PMID- 17217008
TI  - A comparative study of serological techniques for detection of West Nile virus
      antibodies.
AB  - This study was conducted to compare different serological techniques namely
      enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition (HI),
      indirect immunofluorescence (IFT) and plaque reduction neutralization (PRNT), for
      detection of West Nile virus (WNV) antibodies in sera collected from inhabitants
      of a flooded village (Begiram, Minufiya Governorate). ELISA showed 45% while HI
      and IFT indicated 37.6 and 26.4% positive sera among the tested 178 sera taken
      from the flooded village, respectively. The results obtained by ELISA, HI and IFT
      of only 55 randomly chosen sera were compared with their PRNT results. ELISA was
      found to be more sensitive (83.8%) while IFT and HI were more specific (88.9% and
      83.3%, respectively). The positive predictive values for the 3 tests were more
      than 80% while the negative predictive values were different for these tests:
      66.7% for ELISA, 44.1% and 37% for HI and IFT, respectively. From this study it
      is concluded that for screening of population in an endemic area, two serological
      tests in combination can be used starting with ELISA (the more sensitive)
      followed by HI and/or IFT (the more specific) to exclude the false positive
      results.

PMID- 17217009
TI  - Hantaan virus infection among human and rat populations in Alexandria.
AB  - Hantaan virus has recently been identified as the cause of the rodent borne viral
      zoonosis collectively termed Hantavirus disease (HVD). Although the disease is
      mainly endemic in two main areas, clinical forms as well as positive antibody
      testing from healthy persons throughout the world have been reported denoting a
      worldwide presence. Rattus species are almost universally implicated as
      hantavirus reservoirs. Screening for hantavirus antibodies was done on 637
      samples of human sera and 861 rodent sera trapped from 26 locations throughout
      the city of Alexandria, Egypt. ELISA assays were performed and 12.2% of humans
      were found seropositive with no effect of age, duration of work at sea or
      residence on seropositivity. 12.8% of rodents were seropositive with Rattus
      norvegicus showing the highest prevalence and with no influence of sex, age or
      habitat. A significant association was found between the east district and
      seropositivity to Hantaan in rodents.

PMID- 17217010
TI  - Risk factors of anemia among women in the child bearing period and preschool
      children in Alexandria.
AB  - This study was carried out to determine the risk of some social and biological
      maternal factors which may contribute to occurrence of anemia among mothers and
      preschool children. A community based comparative study was chosen for the
      conduction of this work. The target population were 400 women in the child
      bearing period, having at least one preschool child (440). Capillary blood
      samples were taken by finger prick method and hemoglobin level was estimated by
      Sahly method. According to the cut off level of hemoglobin, women were classified
      into anemic and non anemic. In addition to that, 440 preschool children belonging
      to these women were classified according to the cut off level of their hemoglobin
      into 165 anemic children and 275 non anemic ones. An interview questionnaire was
      used to collect the data. Analysis of results showed that age of mother (30 years
      and above), illiteracy, high parity, history of previous abortion, history of
      previous perinatal mortality, small inter-birth interval and non use of
      contraceptives are significant risk factors for mothers. However, mother
      occupation and state of pregnancy has no role in occurrence of anemia among
      mothers. In addition to that, high parity, history of previous abortion, history
      of perinatal mortality, short inter-birth interval, non use of contraceptives and
      pregnancy are maternal risk factors responsible for anemia among preschool
      children. While, mother age, education and occupation has no role for occurrence
      of anemia among preschool children.

PMID- 17217011
TI  - Audiometric pattern in a group of workers with one ear conductive deafness
      exposed to continuous noise.
AB  - BACKGROUND: It is common to find workers in developing countries having residual
      ear problems from childhood affections. When exposed to continuous noise in
      industry, they might exhibit different patterns of audiometric findings. The aim
      of this study was to examine the good ear in a group of workers exposed to
      continuous noise in textile industry with a perforated drum in the other ear from
      childhood otitis media. METHODS: a 1:2 case control design involving a group of
      36 cases and 2 matched groups, same age and duration of exposure was performed. A
      relevant questionnaire was used and each worker was subjected to an audiometric
      test. RESULTS: significantly worse hearing threshold levels at the 250 Hz and the
      4 kHz frequencies were obtained for the good ears of cases compared to controls.
      Subjective complaints were also commoner. A different pattern of hearing loss was
      found adding to the auditory risk of the involved workers.

PMID- 17217012
TI  - Gamma irradiation of Egyptian Cobra (Naja haje) Venom.
AB  - The aim of the present study was to prepare an effective and safe toxoid for the
      Egyptian Cobra (Naja haje) Venom by gamma irradiation. The effects of gamma
      irradiation (0.1-10 M rad) on the toxicity, as well as the antigen antibody
      complex formation reactivity was described. It appears from the results that the
      lethality of Naja haje venom irradiated in the dry form was not affected up to a
      dose of 10 M rad (100 KGy). On the other hand, the venom irradiated in the
      aqueous solution form showed a decrease in its lethality, and this was
      proportionately related to the dose of irradiation, while the ability of the
      venom antigens to react with its corresponding antibodies was retained up to
      irradiation dose of 5 M rad. The results of double immunodiffusion of non
      irradiated and the different dose levels of gamma irradiated venom (0.1-5 M rad)
      against a commercial Egyptian polyvalent antivenin, all showed similar patterns,
      the four visible lines obtained in the immunodiffusion reactions were identical
      and joined smoothly at the corners, indicating that there was no change in
      antigenic reactivity with antibodies determinants.

PMID- 17217013
TI  - Hepatitis E antibodies in Egyptian adolescent females: their prevalence and
      possible relevance.
AB  - Hepatitis E virus has been implicated as a frequent cause of acute sporadic
      hepatitis among Egyptian children. Moreover, an extraordinarily high
      seroprevalence rate was previously reported in a semiurban Nile Delta population.
      A conspicuous feature of hepatitis E is the high morbidity and mortality it can
      cause among infected pregnant women. We therefore evaluated the prevalence of HEV
      antibodies in adolescent females using a solid-phase enzyme linked immunoassay
      based on two recombinant hepatitis E virus antigens. A high prevalence rate
      (38.9%) was found in 95 apparently healthy adolescent females. The mean age of
      the study subjects was 21.81 +/- 2.5 (SD) range 16-25 years. Eighty (84.2%)
      subjects resided in Alexandria, while 15 (15.8%) came from semiurban villages of
      Alexandria Governorate. An increased prevalence was noted with age, as anti-HEV
      antibodies were detected in 32.1% and 41.8% of study participants in the second
      and third decades of life, respectively. Similarly, those illiterate or having
      received less than primary education exhibited a higher HEV prevalence than those
      with higher education (46.3% vs 29.3%). The majority of subjects having
      serological evidence of HEV infection denied previous history of jaundice which
      shows that HEV infection was subclinical in those cases. Ten (55.6%) pregnant
      females participating in the study, as well as 48 (62.3%) non pregnant females
      lacked serological evidence of HEV infection; i.e., 60.01% (10 + 48 out of 95) of
      women in the childbearing age may be susceptible to infection. This report
      suggests that HEV is endemic in Alexandria, Egypt; the epidemiologic risk factors
      associated with HEV infection need further exploration.

PMID- 17217014
TI  - Detection of Herpes Simplex Virus and candida infection with special emphasis on
      their possible role in human Squamous Cell Carcinoma and its variants.
AB  - Sixty seven cases of human oral S.C.C. with its intra oral variances were
      investigated microbiologically, histopathologically, histochemically and
      immunologically. Yeasts were isolated from 85% of examined cases. "Candifast
      test" showed that Candida albicans was the commonest form of the detected fungi,
      followed by C. parapsilosis and C. tropicalis, while the least in frequency was
      the Torulopsis glabrata. Yeasts were more detected in females, elders and tobacco
      smokers. Two cases of well differentiated S.C.C. were surprisingly detected, and
      for the first time in literature, associated with a specific granulomatous
      reaction and showed positively impregnated fungi. While negative reactions for
      fungi were noticed in all lymphoepitheliomas, almost all the verrucous carcinoma
      were positive. Viral inclusion bodies were demonstrated for the first time by MT.
      This method was rapid, economic and could be used as a pilot study before
      applying the more specific monoclonal antibody techniques or in-situ
      hybridization methods. Comparing the results of HSV hybridization with that of
      candida infection we found that both could be detected in some cases. The results
      indicate that viral and fungal factors may be synergetic in the development of
      oral carcinomas.

PMID- 17217015
TI  - Ureaplasma urealyticum as a causative organism of urinary tract infection stones.
AB  - Ureaplasma urealyticum is a fastidious organism which is not recovered by
      conventional bacterial cultures techniques, but special cultures are required for
      its isolation and identification. As it is a urease-producing organism, it is
      considered a risk factor for the formation of struvite calculi in the urinary
      tract. A total of 30 patients with urinary infection stones (19 of them with the
      1st formation and 11 with recurrent stone formation) were included in the study.
      Both bladder urine specimen (cystoscopically obtained) and stones removed were
      subjected to conventional cultures and also to Ureaplasma specific cultures (A7
      agar and U9 broth). The results of culture techniques revealed that 86.7% of
      patients had aerobic organisms (E. coli in 46.7%, Klebsiella in 30%, Proteus in
      6.7% and Pseudomonas in 3.3%) and 26.7% showed U. urealyticum in mid stream
      urine. As regards stone cultures, they revealed aerobic organisms in 76.7%, and
      U. urealyticum in 20%. Sensitivity tests for U. urealyticum showed that
      minocycline was the most effective antimicrobial followed by tetracycline and
      ciprofloxacin. From these data, we conclude that U. urealyticum may be the
      causative organism for infection stone and should be searched for via its
      specific cultures, especially in patients with recurrent stones and with the so
      called sterile pyuria.

PMID- 17217016
TI  - Evaluation of crude and purified Toxocara canis antigens in serodiagnosis of
      human toxocariasis.
AB  - Three serological tests: Immunodiffusion (ID), Counterimmunoelectrophoresis
      (CIEP) and Enzyme-linked immunosorbent assay (ELISA) were used to study the role
      of crude adult worm antigen (CAWA) of Toxocara canis and each of its purified
      fractions in the serodiagnosis of human toxocariasis. Sensitivities of the three
      tests were lower in the ocular than in the visceral group, using different
      antigens. Purified fraction 1 showed more sensitive and specific reactions in the
      three tests, compared to CAWA or purified fraction 2 (P-F2) antigen. The other
      purified fractions (P-F3, P-F4 and P-F5) gave no positive reactions in any of the
      three tests. Using P-F1 antigen, ELISA was the most sensitive technique for
      diagnosis of both visceral and ocular toxocariasis followed by CIEP and then ID
      and the difference was statistically significant. However, CIEP was the most
      specific test followed by ELISA and lastly ID test. The ELISA test using
      Excretory-Secretory (E-S) larval antigen of Toxocara canis was less sensitive
      than the ELISA test using P-F1, although it was 100% specific. Thus, ELISA test
      using P-F1 is the test of choice for diagnosis of human toxocariasis, but when
      the specificity of a reaction is in doubt, CIEP test using the same antigen can
      be of value.

PMID- 17217017
TI  - Monitoring of some pesticides residues in different samples of meat and some
      organs of cattle.
AB  - Intensive use of pesticides for controlling pests in Egypt resulted in presence
      of minute amount of their residue in animal feeds and consequently in animal
      tissues. The present study aimed to monitor the residue of some commonly used
      pesticides in different samples of animal tissues obtained from rural areas. The
      results revealed high concentration of pesticides residue in liver and kidney.

PMID- 17217018
TI  - Assessment and upgrading of knowledge and attitudes among nurses and university
      graduates towards AIDS.
AB  - This study aimed to assess and upgrade the level of knowledge and attitudes
      towards AIDS among nurses and university graduates (U.G.). The study used pre
      test, post-test with no control group design. It was done over a period from
      January 1995 to July 1996. Four hundred and thirty four nurses and 244 U.G. were
      subjected to baseline questionnaire and health education lecture about mean score
      of knowledge and attitudes were significantly improved from pre to post-lecture
      among both groups (p=0.0001). There were no significant differences in the levels
      of knowledge and attitudes pre and post-lecture between the two studied groups,
      or participants' sex (p>O.05). There were statistically significant differences
      between married and single participants with high levels among married (p=0.003).
      Logistic regression analysis showed that marriage was the strongest predictor
      variable of good knowledge score (> or =75%).

PMID- 17217019
TI  - Microbiological profile of raw Nile water.
AB  - With the increase of population on the Nile banks, a remarkable increase in
      industrial, agricultural, human activities, and recreational activities have also
      occurred. The effluents of such activities are discharged directly into the Nile
      or through some agricultural drains which finally discharge their wastes into the
      Nile. Thus, the microbiological monitoring is one of the main objectives to
      protect the river Nile. This study was conducted to determine the microbiological
      profile of river Nile at Cairo segment. Eight sites were chosen along the
      distance (60 Km) from El-Shobak to El-Kanater and tested for two successive years
      (summer 1994-spring 1996). To achieve this goal, microbiological parameters
      (total bacterial counts at both 22 degrees C and 37 degrees C, total coliforms,
      faecal coliforms, faecal streptococci, total yeasts, Candida albicans, Aeromonas
      hydrophila, salmonellae, total staphylococci, total vibrios and Listeria group)
      were evaluated. The results showed that the count of the previous parameters
      ranged between 1.0x10(3)-7.8x10(5) CFU/ml, 5.0x10(2)-6.4x10(5) CFU/ml, 4.9x10
      1.6x10(4) MPN/100 ml, 2.0-5.2x0(3) MPN/100 ml, 2.0x10-1.4x10(3) MPN/100 ml,
      1.7x10(3)-2.6x10(5) CFU/100 ml, 1.5x10(2)-1.7x10(5) CFU/100 ml, 1.0x10(3)
      2.4x10(5) CFU/100 ml, 1.3x10(2)-5.1x10(3) CFU/100 ml, 1.0x10(2)-3.3x10(3) CFU/100
      ml, 1.0x10(2)-3.8x10(4) CFU/100 ml and 1.0x10(2)-1.4x10(5) CFU/100 ml,
      respectively. The total bacterial counts and bacterial indicators (total
      coliforms, faecal coliforms and faecal streptococci) were detected in all samples
      during the period of study, and the count increased in samples collected during
      summer than other seasons. Also total yeasts, A. hydrophila and total
      staphylococci were detected in all samples with differences in count between the
      sites. In contrast, other microbial parameters, Candida albicans, salmonellae,
      total vibrios and Listeria group were not detected in some samples at some sites.
      According to our results it can be concluded that the river Nile is categorized
      as an intermediately polluted river.

PMID- 17217020
TI  - HIV/AIDS knowledge and attitudes among alcohol and drug abusers in Egypt.
AB  - The aim of this study was to assess knowledge, attitudes and practice towards
      HIV/AIDS among alcohol and drug abusers and the effect of health education (HE)
      on their knowledge and attitudes. Participants were 265 substance abusers,
      recruited from 8 addiction rehabilitation centers. A base line study preceding HE
      was done using a questionnaire composed of five sections. Three scores were
      developed to assess HIV/AIDS related knowledge. The base line study indicates
      that addicts with good knowledge scores > or =75%) regarding modes of
      transmission were significantly higher among males than females. About 70% of the
      addicts had negative attitudes towards dealing with HIV/AIDS patients, while
      55.5% felt sympathy for them. Eleven percent of the injection drug abusers were
      sharing needle with others, while 38% of the participating females were
      previously convicted of prostitution. Logistic analysis showed that high level of
      education was the best predictive variable for good knowledge scores (> or =75%).
      Evaluation of the health education program revealed a highly significant increase
      in the knowledge scores among both males and females compared to the pretest
      scores. An increase in the percentages of male and female addicts with improved
      attitudes towards HIV/AIDS patients was also noted after HE. So, HE was found to
      be a successful tool in improving the knowledge and attitudes of substance
      abusers towards HIV/AIDS.

PMID- 17217021
TI  - Newborn care giving by primipara and multipara mothers at home in Tanta City.
AB  - Recent researches are concerned with topics of newborn care giving, maternal
      knowledge and practices because it facilitates growth and development, protection
      against infection and detection of any abnormalities. The purpose of this study
      was to assess the mothers' knowledge and practices of basic newborn care given at
      home. The total sample included 55 primipara and multipara mothers with newborn
      babies. They were selected from Obstetric University Hospital in Tanta City.
      Interview questionnaire and observation checklists were designed to fulfill the
      aim of the study. The study revealed that mothers' knowledge and practices were
      within good and satisfactory average scores in most of the studied items related
      to newborn care giving at home except breast feeding. found between Significant
      differences were primipara and multipara mothers for most of the studied topics
      related to different topics of newborn care giving. practices were within good
      and satisfactory average scores in most of the studied items related to newborn
      care giving at home except breast feeding. Significant differences were found
      between primipara and multipara mothers for most of the studied topics related to
      different topics of newborn care giving.

PMID- 17217022
TI  - Hepatitis B vaccination rates among medical personnel at Ain Shams University
      Hospital and obstacles to vaccine uptake.
AB  - The current study included 1426 medical personnel working at Ain Shams University
      hospitals selected randomly; 354 staff members, 679 junior doctors (residents and
      internships) and 393 nurses. The overall vaccination coverage with at least one
      dose of HB vaccine was 40.6%. The overall coverage with 3 doses of HB vaccine was
      29.1%. The mean number of working years was higher among the vaccinated group.
      More than 55% of personnel who had direct exposure or contact with blood were not
      vaccinated. HB vaccine uptake was conducted at the work place by 65.6% of
      vaccinated personnel and about 50% received the vaccine recently, i.e. less than
      one year. The side effects experienced by vaccinated subjects were local pain
      (5.4%) and headache (0.7%). About 38% of included personnel were not sure about
      the effectiveness of HB vaccine, and 47% do not know exactly the duration of
      vaccine validity. The current price of the vaccine was unaffordable as stated by
      60.9% of subjects and 95.2% concluded that the vaccine should be funded. It was
      recommended that the work place is the best place for HB vaccine uptake by 80.9%
      of subjects and the vaccine should be obligatory for all medical personnel by
      84.3% of subjects.

PMID- 17217023
TI  - Screening tests for diagnosis of cervical lymphadenopathy presenting as prolonged
      fever.
AB  - During a two years period, 16 cases having cervical lymphadenopathy presenting as
      prolonged fever were studied in Abbassia fever hospital, Cairo, Egypt. Patients
      were subjected to careful history, thorough clinical examination, complete blood
      picture, tuberculin test, chest x-ray, Monospot test, indirect fluorescent
      antibody test for toxoplasmosis, detection of cytomegalovirus antibodies and
      lymph node biopsy with histopathological examination. Ten within normal subjects
      were taken as controls. The patients were grouped on histopathological basis into
      5 groups: (1) One (6%) of the cases was non-specific lymphadenitis diagnosed by
      clinical examination of the scalp and leucocytosis with polymorphonuclear
      predominance. (2) Reactive lymphadenitis included 6 (38%) of the cases.
      Infectious mononucleosis cases were diagnosed by clinical triad of fever,
      pharyngitis and cervical lymphadenopathy, relative lymphocytosis, monocytosis and
      positive monospot test. Cytomegalovirus case was diagnosed by lymphocytosis,
      monocytosis and negative monospot test. Toxoplasmosis cases were diagnosed by
      monocytosis, negative tuberculin test and positive indirect fluorescent antibody
      test. (3) Granulomatous lymphadenitis comprised 6 (3%) of the cases. Tuberculous
      cases were diagnosed by high ESR and highly positive tuberculin test. Sarcoidosis
      cases were diagnosed by negative tuberculin test and presence of hilar
      lymphadenopathy. (4) Non-Hodgkin lymphoma case (6%) was diagnosed by clinical
      deterioration and total lymph node biopsy. 15) Systemic infections were diagnosed
      by clinical examination, blood culture for salmonellae and brucellae, Widal and
      Brucella agglutination tests. It is concluded from this study that screening
      tests are important aids in the diagnosis of cases of cervical lymphadenopathy
      presenting by prolonged fever especially if lymph node biopsy and
      histopathological examination are not available or contraindicated. Tub

PMID- 17217024
TI  - Infectious diseases among food handlers.
AB  - trichiura was the most common infection in the studied group. Continuous follow
      up and health education of food handlers have led to avoidance of outbreaks of
      infections among food consumers in the hospital. This study was carried out to
      find the prevalence and associated factors of communicable diseases especially
      parasitic infections among food handlers in King Fahd Hospital, Jeddah, Saudi
      Arabia, for early detection and proper management. This study was conducted as a
      preemployment examination on 52 new kitchen male workers with a mean age of
      26.77+/-5.03 years. They were subjected to complete medical examination as well
      as some general and specific laboratory investigations as a food handler. Results
      of throat swab showed that 12% of the studied group were positive for group A
      beta haemolytic streptococci. Parasitological examination showed that seven
      subjects (13.5%) were infected. Out of them 3 only had single parasitic
      infections and 4 had double infections. Trichuris trichiura was the most common
      infection in the studied group. Continuous follow up and health education of food
      handlers have led to avoidance of outbreaks of infections among food consumers in
      the hospital.

PMID- 17217025
TI  - Health hazards among workers in power stations. Comparative study between natural
      gas and mazout stations.
AB  - This study was done on 65 workers working in power station I (Shoubra El-Kheima)
      where they are exposed to natural gas and mazout, 74 workers in power station II
      (El-Gharb) where there is mazout exposure only and 74 individuals acting as
      controls. All these individuals were admitted to a questionnaire, examined
      clinically and they were investigated to assess their respiratory, liver and
      kidney function tests. This is in addition to a complete blood picture. Air
      pollution inside these stations was assessed. The study aimed at determining the
      pollutants inside and outside the stations and to investigate the health hazards
      of the workers exposed to these pollutants. It aimed also to see if it is
      important and urgent to replace the mazout by natural gas as a fuel in these
      power stations. The results showed that by-products of mazout have bad effect on
      the environment. When mazout is used alone as a fuel, it has an adverse effect on
      the respiratory system and the liver. There is a need for a prospective study to
      assess the causal relationship between mazout by-products and health hazards
      before taking the decision of replacing mazout by natural gas.

PMID- 17217026
TI  - Detection of hepatitis E virus in greater Cairo. Two wastewater treatment plants
      and its prevalence among workers of these plants.
AB  - Because of inadequate public sanitation, epidemics of HEV infection have been
      reported in several developing countries. HEV-specific cDNA was prepared by
      reverse transcription of the total RNA extracted from water samples. Specified
      DNA amplification by POR demonstrates the presence of HEV in sewage samples from
      the inlets (PCR positive 10/36:27.77%), while outlet samples were PCR negative.
      HEV 1gM was detected in 40 workers out of 78 in these two studied plants (age 20
      60 years), with a percentage of 51.25% and HAV 1gM was also detected in 3 workers
      out of 78 (3.84%). The study of serum ALT and albumin level go with the increase
      in HEV 1gM in sera. This study which was carried out in two different wastewater
      treatment plants showed that HEV contamination was higher in one of them (El
      Berka) than El-Zenin. A total of 33.33% of influent water samples were positive
      and 55.25% of workers were HEV 1gM positive in the first plant (El-Berka) and the
      corresponding figure in the other plant (El-Zenin) showed lower contamination,
      22.22% in influent water sample and 40.9% of workers.

PMID- 17217027
TI  - Identification of Acanthamoeba strains isolated from a freshwater course in Saudi
      Arabia.
AB  - A total of 40 freshwater samples, collected from Wadi Hanifah, were cultured on
      non-nutrient agar + 1% NaCl for the detection of Acanthamoeba. Thirty three
      strains of Acanthamoeba were isolated and subcultured for further identification
      according to cyst morphology. The isolated strains of Acanthamoeba were found
      belonging to 4 species which were A. astronyxis, A. comandoni, A. culbertsoni and
      A. quina. The optimum and maximum tolerated temperatures for growth as well as
      the pathogenicity of each strain for mice were also recorded. This water source
      is hazardous for human use.

PMID- 17217028
TI  - A three-level hearing screening program for school children.
AB  - This study reports the results of a hearing screening program that was conducted
      in a number of schools in Alexandria region in the school year 1997-1998. Schools
      were classified according to location into urban and suburban schools. Screening
      was done in three separate levels. In the first level, screening was done by
      health visitors in classrooms. To pass the screening in this level, the student
      had to indicate hearing of 30, 30, 25 & 25 dB tones at 1000, 2000, 4000 & 8000
      Hz, respectively. A total of 6180 students were screened in this level, and only
      10% of them (614 students) failed. The failing students were referred for the
      second level of screening in Sporting Hospital for School Students. The screening
      was done by trained health visitors in sound treated rooms, and to pass this
      level the child had to indicate hearing of 25 dB tones at 250, 500, 1000, 2000,
      4000 & 8000 Hz. From 225 students who attended this level, only 75 students
      passed. The failing students were assumed to have a hearing problem and were
      referred for audiologic diagnosis by a consultant audiologist in the third level.
      The number of students attending the third level were 67 students and all of them
      had a hearing deficit. In 44 of them occluding wax was the cause of failure and
      upon its removal they proved to have normal hearing. Twenty three students had
      hearing loss due to secretory otitis media, chronic suppurative otitis media, or
      sensory neural hearing loss. The estimated prevalence of hearing loss in school
      children in this study ranged between 1.17 and 2.59%.

PMID- 17217029
TI  - Response and effect of two plant crude extracts on mosquito larvae Culex pipiens.
AB  - The response and effect of two plant crude extract from dry Damsissa (Ambrosia
      maritima) and Neem seeds (Azadirachta indica) were tested against the first and
      third instar larvae of mosquito (Culex pipiens). The results showed that both
      extracts had a larvicidal effect. Neem seed extract was more toxic than Damsissa
      extract against both the first and third instar larvae. In addition, the young
      larvae (first instar) were more susceptible to Neem seeds than the old ones
      (third instar) as revealed from the LC50 values, while Damsissa showed nearly the
      same effect against both stages. Meanwhile, treatment of Neem seed extracts
      resulted in prolongation of the larval period accompanied with a decrease in
      larval activity. Moreover, the effect of the two extracts on larval total
      esterase isozymes was examined. Neem extract showed an adverse effect on the
      third instar larvae, since only one band (E1) was observed and the other 4 bands
      disappeared at all concentrations used, as compared with untreated control larvae
      (El, E2, E3, E4, and E5). Meanwhile, Damsissa extract treatment of the third
      instar larvae showed an additional band located between E3 and E4, and the
      absence of two bands (E2 and E3) after treatment with 0.5x10(4), 1x10(4) and
      1.5x10(4) ppm, while treatment with 0.25x10(4) ppm did not result in any changes
      in larval total esterase.

PMID- 17217030
TI  - Epidemiology of school injuries in Alexandria.
AB  - This study was conducted to reveal the magnitude of school injuries in
      Alexandria, their epidemiological patterns and outcomes. All pupils attending the
      casualty department of Alexandria Students' Hospital during the scholastic year
      1996-1997 with school injuries were included in this study. An interview
      questionnaire and a transfer sheet were used to collect relevant information.
      Data were analyzed and the 5% level was taken to judge the significance of the
      obtained results. During the study period, 3422 pupils sustained school injuries
      yielding a rate of 4.25 per 1000. This rate was significantly higher among boys
      (6.43 per 1000) as well as in secondary schools (8.11 per 1000). Most of these
      injuries occurred inside the school (72.0%). In relation to school activity,
      injuries occurred more frequently during breaks (28.1%), school trips (27.8%) and
      teaching sessions (25.6%). Falls were responsible for 52.3% of the injuries
      followed by struck by or against (25.2%), while 11.9% were due to road traffic
      accidents. The most commonly affected sites were the upper (46.2%) and lower
      (32.1%) limbs as well as the head and neck (16.6%). High proportions of the
      resulting injuries were minor, however, severe injuries namely, fractures (23.2%)
      and brain concussions (2.8%) were encountered. Significant differences were
      observed in this respect in relation to the pupils' gender and educational stage.
      Only 12.5% of the cases were hospitalized. All recovered completely except four
      cases of leg amputation and no deaths were recorded. School injuries appear to be
      a priority area for primary preventive activities. School personnel should
      receive safety rounds to recognize the potential environmental hazards. Stringent
      supervision is required in areas and during activities with high frequency of
      injuries. Moreover, safety education should be incorporated in the curriculum and
      activities involving school children.

PMID- 17217031
TI  - The effect of dimethylnitrosamine on the activities of renal
      prenolsulfotransferase and arylsulfatases A and B in Schistosona mansoni infected
      mice.
AB  - The activities of renal phenolsulfotransferase and arylsulfatases A and B were
      estimated in 400 male Swiss albino mice classified into four groups: Normal
      controls, Schistosoma mansoni infected group, Dimethylnitrosamine (DMN) treated
      group and infected treated group. The activity levels of the studied enzymes were
      significantly increased in all groups when compared with the control group, also
      the statistical analyses showed a high significant increase of the three enzymes
      levels in the infected treated group; when compared separately with treated or
      infected groups. It was concluded, therefore, that schistosomal infection is
      implicated in the development of kidney cancer which may arise from the pattern
      of hepatic mixed-function oxidase induction characterized for schistosomiasis and
      its temporal relationship with the procarcinogenic initiating events.
      Furthermore, the striking significant increase in the enzymatic activity levels
      of the acid hydrolases arylsulfatases due to the lesion of both cytotoxic effects
      of dimethylnitrosamine as well as pathological change of schistosomiasis which
      may play an active role in the initiation of the malignant process by detoxifying
      endogenous sulfated aromatic metabolites.

PMID- 17217032
TI  - Hepatitis B and C virus infections among patients with gingivitis and adult
      periodontitis: seroprevalence and public health importance.
AB  - The aim of the present case control study was to identify seroprevalence of
      hepatitis B and C virus (HBV and HCV) infections among one hundred cases with
      periodontal disease (71% gingivitis and 29% adult periodontitis) and one hundred
      controls with healthy gingiva matdhed for age and sex. Moreover, it aimed to
      detect hepatitis markers in saliva samples corresponding to the positive sera.
      Different risk factors associated with hepatitis infection and detectability rate
      of hepatitis markers were also studied. METHODOLOGY: enzyme linked immunosorbent
      assay (ELISA) technique was used to detect the presence of hepatitis B surface
      antigen (HBsAg), antibody to hepatitis B core antigen (anti HBc), e antigen (eAg)
      and antibody to hepatitis C virus (anti HCV) both in serum and saliva samples.
      HCV RNA was detected by polymerase chain reaction (PCR) technique. Oral
      examination was performed for assessment of simplified Oral Hygiene Index (OHI
      S), Papillary Bleeding Index (PBI), probing pocket depth and loss of fibre
      attachment. RESULTS: cases with periodontal disease showed higher percentages of
      hepatitis exposure (hepex; anti HCV and/or anti HBc) and significantly higher
      anti HCV seropositivity than the controls (26% and 13% versus 22% and 8%,
      respectively). No difference in HBsAg carrier rate nor in anti HBc seropositivity
      was elicited. Furthermore, cases with periodontal disease showed higher
      detectability rate of HBsAg, anti HBc, anti HCV or both anti HCV and/or anti HBc
      in whole unstimulated saliva than the controls (100% vs 66.7%, 50% vs 23.5%,
      23.1% vs 0.0% and 42.3% vs 18.2%, respectively). Stepwise logistic regression
      delineated two significant factors associated with the risk of hepatitis
      exposure, the first predictor was the rural residence and the second one was the
      history of blood transfusion (OR=3.10, 2.94, respectively). Periodontal disease,
      severity of bleeding and bad oral hygiene were associated with the risk of
      hepatitis infection and with the detectability of hepatitis markers in the whole
      saliva.

PMID- 17217033
TI  - Impact of National Schistosomiasis Control Program in Kafr El-Sheikh governorate,
      Nile Delta, Egypt: an independent evaluation.
AB  - A longitudinal study has been conducted (1991-1997) to evaluate the impact of
      repeated selective chemotherapy on human transmission indices of Schistosoma
      mansoni infection. The study population included 8370 individuals inhabiting four
      villages and their satellites and representing high and low S. mansoni endemicity
      communities in Kafr EI-Sheikh governorate. A parasitological survey was conducted
      for three successive years (1991-1992 and 1993). Each time infected received
      praziquantel (PZQ) chemotherapy. In 1997, a fourth parasitological survey was
      done. During the period from 1994-1996 only routine diagnosis and treatment of
      schistosomiasis offered by the Ministry of Health and Population (MOHP) was going
      on. Study results revealed a decrease in S. mansoni prevalence and intensity of
      infection in the first three years. The drop was marked after the first year. In
      1997, after the cessation of active case finding and treatment by the project
      team, an upward trend was observed for both prevalence and geometric mean egg
      count (GMEC) especially for the high prevalence villages. However, all indices
      were kept at significant low levels as compared to base-line values in 1991.

PMID- 17217034
TI  - Improving students' knowledge, attitude and practice towards cancer prevention
      through a health education program. Part II.
AB  - A health education program for cancer risk reduction was conducted among 649
      students out of 896 for whom Knowledge, Attitude and Practice (KAP) had been
      obtained at the initial study. Three hundred and sixteen students acted as the
      intervented group and three hundred and thirty three were the control group.
      There was a great improvement in the percentage of correct knowledge answers in
      the majority of the questions from pre to post tests especially for the questions
      about the effect of excessive use of fatty foods (76.3%) and excessive use of
      salty foods (68.0%) on the occurrence of cancer. After the program, at least 87%
      or more of the students recognized the hazards of risky food, 86.1% knew that
      mothers who do not breast feed their infants have a greater chance of getting
      cancer breast, 51.3% responded correctly to the question about the effect of oral
      contraceptive pills after 40 years. More than 86% recognized the serious effect
      of prolonged exposure to the sun. A significant shift toward positive attitude
      was found especially with the item "I am very afraid to know that I have cancer,
      so I avoid going to the physician" (76.9%). It was found that 94% of the students
      agreed that there is a relation between the type of food and cancer. The students
      showed significant increases in median practice scores from pre to post tests and
      the larger gain associated with participants in the program (9.97%). The majority
      of the students reported increases in their daily consumption of fruits, cereals,
      leafy vegetables and salad. These significant changes in KAP scores from pre to
      post tests were noticed for both sexes, different social classes and different
      educational grades.

PMID- 17217035
TI  - APL as a paradigm in biomedical research: a journey toward the cure.

PMID- 17217036
TI  - Mouse models of acute promyelocytic leukemia.
AB  - Mouse models of acute promyelocytic leukemia have been generated through
      transgenic, knock-in, retroviral, and xenograft strategies. These models have
      been used to elucidate mechanisms underlying leukemogenesis. Among the areas
      investigated are the role of reciprocal fusions; effects of target cells,
      expression levels, and mouse strains; cooperating events; and restrictive and
      permissive factors. These models have also been used to gain insight into the
      effects of the immune system on leukemic cells and the mechanism of response to
      retinoic acid. Furthermore, preclinical studies utilizing these mice have
      advanced therapy for myeloid leukemia.

PMID- 17217037
TI  - The PLZF gene of t (11;17)-associated APL.
AB  - The PLZF gene is one of five partners fused to the retinoic acid receptor alpha
      in acute promyelocytic leukemia. PLZF encodes a DNA-binding transcriptional
      repressor and the PLZF-RARalpha fusion protein like other RARalpha fusions can
      inhibit the genetic program mediated by the wild tpe retinoic acid receptor.
      However an increasing body of literature indicates an important role for the PLZF
      gene in growth control and development. This information suggests that loss of
      PLZF function might also contribute to leukemogenesis.

PMID- 17217038
TI  - SUMO, the three Rs and cancer.
AB  - SUMO modification (sumoylation) plays important roles in nucleo-cytoplasmic
      transport, maintenance of sub-nuclear architecture, the regulation of gene
      expression and in DNA replication, repair and recombination. Here we review
      recent evidence for SUMO's role in protecting genomic integrity at both the
      chromosomal and the DNA level. Furthermore, the involvement of sumoylation and of
      specific SUMO targets in cancer is discussed.

PMID- 17217039
TI  - Emerging role for microRNAs in acute promyelocytic leukemia.
AB  - Hematopoiesis is highly controlled by lineage-specific transcription factors
      that, by interacting with specific DNA sequences, directly activate or repress
      specific gene expression. These transcription factors have been found mutated or
      altered by chromosomal translocations associated with leukemias, indicating their
      role in the pathogenesis of these malignancies. The post-genomic era, however,
      has shown that transcription factors are not the only key regulators of gene
      expression. Epigenetic mechanisms such as DNA methylation, posttranslational
      modifications of histones, remodeling of nucleosomes, and expression of small
      regulatory RNAs all contribute to the regulation of gene expression and
      determination of cell and tissue specificity. Deregulation ofthese epigenetic
      mechanisms cooperates with genetic alterations to the establishment and
      progression of tumors. MicroRNAs (miRNAs) are negative regulators of the
      expression of genes involved in development, differentiation, proliferation, and
      apoptosis. Their expression appears to be tissue-specific and highly regulated
      according to the cell's developmental lineage and stage. Interestingly, miRNAs
      expressed in hematopoietic cells have been found mutated or altered by
      chromosomal translocations associated with leukemias. The expression levels of a
      specific miR-223 correlate with the differentiation fate of myeloid precursors.
      The activation of both pathways of transcriptional regulation by the myeloid
      lineage-specific transcription factor C/EBPalpha (CCAAT/enhancer-binding protein
      alpha), and posttranscriptional regulation by miR-223 appears essential for
      granulocytic differentiation and clinical response of acute promyelocytic
      leukemia (APL) blasts to all-trans retinoic acid (ATRA). Together, this evidence
      underlies transcription factors, chromatin remodeling, and miRNAs as ultimate
      determinants for the correct organization of cell type-specific gene arrays and
      hematopoietic differentiation, therefore providing new targets for the diagnosis
      and treatment of leukemias.

PMID- 17217040
TI  - The theory of APL revisited.
AB  - Acute promyelocytic leukemia (APL) is associated with reciprocal and balanced
      chromosomal translocations always involving the retinoic acid receptor alpha
      (RARa) gene on chromosome 17 and variable partner genes (X genes) on distinct
      chromosomes. RARalpha fuses to the PML gene in the majority of APL cases, and in
      a few cases to the PLZF, NPM, NuMA and STAT5b genes. As a consequence, X-RARalpha
      and RARalpha-X fusion genes are generated encoding aberrant chimeric proteins
      that exert critical oncogenic functions. Here we will integrate some of the most
      recent findings in APL research in a unified model and discuss some of the
      outstanding questions that remain to be addressed.

PMID- 17217041
TI  - Treatment of acute promyelocytic leukemia by retinoids.
AB  - We review the role of all-trans retinoic acid (ATRA) in the treatment of acute
      promyelocytic leukemia (APL). The combination of ATRA and conventional
      anthracycline-ARA-C chemotherapy (CT) has clearly demonstrated its superiority
      over CT alone (in terms of relapse and survival) in newly diagnosed APL.
      Combination treatment probably also reduces the incidence of initial failures,
      and complete remission (CR) rates greater than 90% are now regularly reported in
      large multicenter trials. Some randomized studies strongly suggest that prolonged
      maintenance treatment (for 1 or 2 years) with ATRA and low-dose CT, and possibly
      very early introduction of anthracycline CT during induction treatment, may
      reduce the incidence of relapse. With those treatments, the relapse risk appears
      to be only 10%-15%, although it remains greater in patients who initially have
      high white blood cell counts (often associated with variant M3 morphology, short
      bcr3 isoform, etc.) and patients with residual disease detectable by RT-PCR at
      the end of consolidation courses. In those patients, addition of arsenic
      derivatives to induction or consolidation treatment (or both treatments together)
      may prove useful and is currently being tested. ATRA syndrome (now generally
      called APL differentiation syndrome, as it is also seen with arsenic derivatives)
      remains the major side effect of ATRA treatment. It occurs in 10%-15% of patients
      and is currently fatal in at least 10% of them. Rapid onset of CT or high dose
      steroids (or both) should improve its outcome. A sizeable proportion of APL
      patients who relapse after ATRA and CT can be durably salvaged by the same
      treatment followed by allogeneic or autologous stem cell transplantation,
      provided the transplant (in the autologous setting) is RT-PCR-negative. However,
      in relapsing APL arsenic derivatives (mainly arsenic trioxide) are now considered
      to be the reference treatment. Some of the current issues with ATRA treatment in
      newly diagnosed APL include whether ATRA has a role during consolidation
      treatment and whether arabinoside (AraC) is required in addition to
      anthracyclines in the chemotherapy combined to ATRA.

PMID- 17217042
TI  - Arsenic trioxide and acute promyelocytic leukemia: clinical and biological.
AB  - Arsenic has recently been identified as an effective drug in the treatment of
      newly diagnosed and relapsed acute promyelocytic leukemia. Indeed, arsenic
      trioxide combined with all-trans retinoic acid shows a synergistic effect.
      Mechanistically, arsenic targets the key leukemogenic protein PML-RARalpha,
      setting up a new example of molecular target-based cancer therapy.

PMID- 17217043
TI  - Front line clinical trials and minimal residual disease monitoring in acute
      promyelocytic leukemia.
AB  - In spite of the very high cure rate (70%-80%) achieved in APL with combinatorial
      all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy regimens, a
      number of issues are still open for investigation in front-line therapy of this
      disease. These include, among others, improvements in early death rate, the role
      of arsenic trioxide (ATO) and maintenance treatment, and, finally, optimization
      of molecular monitoring to better identify patients at increased risk of relapse.
      The current consensus on the most appropriate induction therapy consists of the
      concomitant administration of ATRA and anthracycline-based chemotherapy. Although
      the antileukemic benefit provided by the addition of ATRA to consolidation
      therapy has not been demonstrated in randomized studies, historical comparisons
      of consecutive studies carried out by Spanish and Italian cooperative groups
      suggest that the combination of ATRA and chemotherapy for consolidation may also
      contribute to improving therapeutic results. While a variety of distinct
      treatments are being investigated for front-line therapy, most experts agree that
      a risk-adapted therapy represents the optimal approach, through the use of more
      intensive therapy in patients with initial hyperleukocytosis. Longitudinal RT-PCR
      of PML/RARalpha allows sensitive assessment of response to treatment and minimal
      residual disease (MRD) monitoring in APL. Achievement of negative PCR status or
      molecular remission at the end of consolidation is now universally accepted and
      recommended as a therapeutic objective in this disease. On the other hand,
      persistence of, or conversion to, PCR positive in the marrow during follow-up is
      associated with impending relapse. Preliminary studies on therapy of molecular
      relapse indicate a survival advantage as compared to administering salvage
      treatment at time of hematologic relapse. The more accurate and reproducible real
      time PCR method to detect at quantitative levels the PML/RARalpha hybrid will
      likely provide better inter-laboratory standardization and trial results
      comparison in the near future.

PMID- 17217044
TI  - Histone deacetylase inhibitors in APL and beyond.
AB  - In recent years the study of chemical modifications to chromatin and their
      effects on cellular processes has become increasingly important in the field of
      cancer research. Disruptions to the normal epigenetic pattern of the cell can
      serve as biomarkers and are important determinants of cancer progression.
      Accordingly, drugs that inhibit the enzymes responsible for modulating these
      epigenetic markers, in particular histone deacetylases, are the focus of intense
      research and development. In this chapter we provide an overview of class I and
      II histone deacetylases as well as a guide to the diverse types of histone
      deacetylase inhibitors and their activities in the context of APL. We also
      discuss the rationale for the use of histone deacetylase inhibitors in
      combination therapy for the treatment of cancer and the current status of
      clinical trials.

PMID- 17217045
TI  - Monoclonal antibody therapy of APL.
AB  - Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia
      (AML) for which a number of targeted therapies have been developed. The "targets"
      have included both genotypic and phenotypic features of the disease. The
      application of monoclonal antibodies (MAbs) to this disease to date have been
      limited to a relatively small number of studies where this therapy has been used
      to supplement effective approaches to the disease. The preliminary results have
      been promising, and further development of this modality as an effective adjunct
      to existing treatment regimens will most certainly occur in the near future.

PMID- 17217046
TI  - Targeting APL fusion proteins by peptide interference.
AB  - A significant barrier to experimental therapeutics is the ability to identify and
      specifically target oncogenic proteins involved in the molecular pathogenesis of
      disease. In acute promyelocytic leukemia (APL), aberrant transcription factors
      and their associated machinery play a central role in mediating the malignant
      phenotype. The mechanism of action of APL chimeric fusion proteins involves their
      ability to either self-associate or interact with different partner proteins.
      Thus, targeting protein-protein interactions could have a significant impact in
      blocking the activity of APL oncoproteins. As therapeutic targets, the interface
      between interacting proteins may not always be amenable to highly specific small
      molecule blockade. In contrast, peptides are well-suited to this purpose and can
      be reliably delivered when fused to cell-permeable peptide domains. Therapeutic
      peptides can be designed to directly target APL fusion proteins, their downstream
      effectors, or other potentially synergistic oncogenic mechanisms of importance in
      APL blasts. In addition to serving as potential therapeutic agents, such reagents
      could serve as powerful reagents to dissect the molecular pathogenesis of APL.

PMID- 17217047
TI  - The design of selective and non-selective combination therapy for acute
      promyelocytic leukemia.
AB  - Acute promyelocytic leukemia (APL) is an unique subtype of acute myeloid leukemia
      typically carrying a specific reciprocal chromosome translocation, t(15;17),
      leading to the expression of a leukemia-generating fusion protein, PML-RARalpha.
      APL patients are responsive to APL-selective reagents such as all-trans retinoic
      acid (ATRA) or arsenic trioxide and non-selective cytotoxic chemotherapy. Nearly
      all de novo APL patients undergo clinical remission when treated with ATRA plus
      chemotherapy or with the combinational selective therapy, ATRA plus As2O3.
      Combining ATRA with As2O3 as an induction followed by chemotherapy consolidation
      results in more profound clinical remissions compared to treatment with any agent
      alone or any of the other possible combinations. The mechanism of action of each
      of these agents differs. ATRA induces APL cell differentiation and PML-RARalpha
      proteolysis. As2O3 induces APL cell partial differentiation, PML-RARalpha
      proteolysis, and apoptosis. Chemotherapy, mainly using anthracyclines, induces
      APL cell death. The combined effects of selective APL therapy (ATRA and As2O3)
      and/or non-selective chemotherapy in APL cells in vitro and their mechanisms in
      relation to clinical protocol design are discussed.

PMID- 17217048
TI  - An introduction on TRP channels.
AB  - The transient receptor potential (TRP) ion channels are named after the role of
      the channels in Drosophila phototransduction. Mammalian TRP channel subunit
      proteins are encoded by at least 28 genes. TRP cation channels display an
      extraordinary assortment of selectivities and activation mechanisms, some of
      which represent previously unrecognized modes of regulating ion channels. In
      addition, the biological roles of TRP channels appear to be equally diverse and
      range from roles in thermosensation and pain perception to Ca2+ and Mg2+
      absorption, endothelial permeability, smooth muscle proliferation and gender
      specific behaviour.

PMID- 17217049
TI  - TRPC1 Ca(2+)-permeable channels in animal cells.
AB  - The full-length transient receptor (TRPC)1 polypeptide is composed of about 790
      amino acids, and several splice variants are known. The predicted structure and
      topology is of an integral membrane protein composed of six transmembrane
      domains, and a cytoplasmic C- and N-terminal domain. The N-terminal domain
      includes three ankyrin repeat motifs. Antibodies which recognise TRPC1 have been
      developed, but it has been difficult to obtain antibodies which have high
      affinity and specificity for TRPC1. This has made studies of the cellular
      functions of TRPC1 somewhat difficult. The TRPC1 protein is widely expressed in
      different types of animal cells, and within a given cell is found at the plasma
      membrane and at intracellular sites. TRPC1 interacts with calmodulin, caveolin-1,
      the InsP3 receptor, Homer, phospholipase C and several other proteins.
      Investigations of the biological roles and mechanisms of action of TRPC1 have
      employed ectopic (over-expression or heterologous expression) of the polypeptide
      in addition to studies of endogenous TRPC1. Both approaches have encountered
      difficulties. TRPC1 forms heterotetramers with other TRPC polypeptides resulting
      in cation channels which are non-selective. TRPC1 may be: a component of the pore
      of store-operated Ca2+ channels (SOCs); a subsidiary protein in the pathway of
      activation of SOCs; activated by interaction with InsP3R; and/or activated by
      stretch. Further experiments are required to resolve the exact roles and
      mechanisms of activation of TRPC1. Cation entry through the TRPC1 channel is feed
      back inhibited by Ca2+ through interaction with calmodulin, and is inhibited by
      Gd3+, La3+, SKF96365 and 2-APB, and by antibodies targeted to the external mouth
      of the TRPC1 pore. Activation of TRPC1 leads to the entry to the cytoplasmic
      space of substantial amounts of Na+ as well as Ca2+. A requirement for TRPC1 is
      implicated in numerous downstream cellular pathways. The most clearly described
      roles are in the regulation of growth cone turning in neurons. It is concluded
      that TRPC1 is a most interesting protein because of the apparent wide variety of
      its roles and functions and the challenges posed to those attempting to elucidate
      its primary intracellular functions and mechanisms of action.

PMID- 17217050
TI  - TRPC2: molecular biology and functional importance.
AB  - TRPC (canonical transient receptor potential) channels are the closest mammalian
      homologs of Drosophila TRP and TRP-like channels. TRPCs are rather nonselective
      Ca2+ permeable cation channels and affect cell functions through their ability to
      mediate Ca2+ entry into cells and their action to collapse the plasma membrane
      potentials. In neurons the latter function leads to action potentials. The
      mammalian genome codes for seven TRPCs of which TRPC2 is the largest with the
      most restricted pattern of expression and has several alternatively spliced
      variants. Expressed in model cells, TRPC2 mediates both receptor- and store
      depletion-triggered Ca2+ entry. TRPC2 is unique among TRPCs in that its complete
      gene has been lost from the Old World monkey and human genomes, in which its
      remnants constitute a pseudogene. Physiological roles for TRPC2 have been studied
      in mature sperm and the vomeronasal sensory system. In sperm, TRPC2 is activated
      by the sperm's interaction with the oocyte's zona pellucida, leading to entry of
      Ca2+ and activation of the acrosome reaction. In the vomeronasal sensory organ
      (VNO), TRPC2 was found to constitute the transduction channel activated through
      signaling cascade initiated by the interaction of pheromones with V1R and V2R G
      protein-coupled receptors on the dendrites of the sensory neurons. V1Rs and V2Rs,
      the latter working in conjunction with class I MHC molecules, activate G(i)- and
      G(o)-type G proteins which in turn trigger activation of TRPC2, initiating an
      axon potential that travels to the axonal terminals. The signal is then projected
      to the glomeruli of the auxiliary olfactory bulb from where it is carried first
      to the amygdala and then to higher cortical cognition centers.
      Immunocytochemistry and gene deletion studies have shown that (1) the V2R-G(o)
      MHCIb-beta2m pathway mediates male aggressive behavior in response to pheromones;
      (2) the V1R-G(i2) pathway mediates mating partner recognition, and (3) these
      differences have an anatomical correlate in that these functional components are
      located in anatomically distinct compartments of the VNO. Interestingly, these
      anatomically segregated signaling pathways use a common transduction channel,
      TRPC2.

PMID- 17217051
TI  - TRPC3: a multifunctional, pore-forming signalling molecule.
AB  - TRPC3 represents one of the first identified mammalian relatives of the
      Drosophila trp gene product. Despite intensive biochemical and biophysical
      characterization as well as numerous attempts to uncover its physiological role
      in native cell systems, this channel protein still represents one of the most
      enigmatic members of the transient receptor potential (TRP) superfamily. TRPC3 is
      significantly expressed in brain and heart and likely to play a role in both non
      excitable as well as excitable cells, being potentially involved in a wide
      spectrum of Ca2+ signalling mechanisms. Its ability to associate with a variety
      of partner proteins apparently enables TRPC3 to form different cation channels in
      native cells. TRPC3 cation channels display unique gating and regulatory
      properties that allow for recognition and integration of multiple input stimuli
      including lipid mediators and cellular Ca2+ gradients as well as redox signals.
      The physiological/pathophysiological functions of this highly versatile cation
      channel protein are as yet barely delineated. Here we summarize current knowledge
      on properties and possible signalling functions of TRPC3 and discuss the
      potential biological relevance of this signalling molecule.

PMID- 17217052
TI  - Ionic channels formed by TRPC4.
AB  - TRPC4 (transient receptor potential canonical 4) is a member of the TRPC sub
      family and, within this sub-family, TRPC4 is most closely related to TRPC5. A
      number of splice variants of TRPC4 have been identified, whereby TRPC4alpha and
      TRPC4beta appear to be the most abundant isoforms in various species. TRPC4alpha
      comprises six transmembrane segments and the N- and C-termini are located
      intracellularly. Additionally, TRPC4alpha shares other structural features with
      members of the TRPC sub-group, including ankyrin-like repeats, coiled-coil
      regions and binding sites for calmodulin and IP3 receptors. Three calmodulin
      binding domains have been identified in the C-terminus of TRPC4alpha. TRPC4beta
      lack 84 amino acids in the C-terminus, which correspond to the last two
      calmodulin-binding sites of TRPCalpha. The first and last calmodulin-binding
      domains of TRPC4alpha overlap with binding sites for the N- and C-termini of IP3
      receptors. The ionic channels formed by TRPC4 appear to be Ca(2+)-permeable,
      although there is a considerably discrepancy in the degree of Ca2+ selectivity.
      Studies with mice lacking TRPC4 (TRPC4(-/-)) suggest an important role for TRPC4
      in supporting Ca2+ entry. The defect in Ca2+ entry in TRPC4(-/-) mice appears to
      be associated with a reduction of the vasorelaxation of arteries, vascular
      permeability in the lung and neurotransmitter release from thalamic dendrites.

PMID- 17217053
TI  - Canonical transient receptor potential 5.
AB  - Canonical transient receptor potential 5 TRPC5 (also TrpC5, trp-5 or trp5) is one
      of the seven mammalian TRPC proteins. Its known functional property is that of a
      mixed cationic plasma membrane channel with calcium permeability. It is active
      alone or as a heteromultimeric assembly with TRPC1; TRPC4 and TRPC3 may also be
      involved. Multiple activators of TRPC5 are emerging, including various G protein
      coupled receptor agonists, lysophospholipids, lanthanide ions and, in some
      contexts, calcium store depletion. Intracellular calcium has complex impact on
      TRPC5, including a permissive role for other activators, as well as inhibition at
      high concentrations. Protein kinase C is inhibitory and mediates desensitisation
      following receptor activation. Tonic TRPC5 activity is detected and may reflect
      the presence of constitutive activation signals. The channel has voltage
      dependence but the biological significance of this is unknown; it is partially
      due to intracellular magnesium blockade at aspartic acid residue 633. Protein
      partners include calmodulin, CaBP1, enkurin, Na(+)-H+ exchange regulatory factor
      (NHERF) and stathmin. TRPC5 is included in local vesicular trafficking regulated
      by growth factors through phosphatidylinositol (PI)-3-kinase, Rac1 and PIP-5
      kinase. Inhibition of myosin light chain kinase suppresses TRPC5, possibly via an
      effect on trafficking. Biological roles of TRPC5 are emerging but more reports on
      this aspect are needed. One proposed role is as a mediator of calcium entry and
      excitation in smooth muscle, another as an inhibitor of neuronal growth cone
      extension. The latter is intriguing in view of the original cloning of the human
      TRPC5 gene from a region of the X chromosome linked to mental retardation. TRPC5
      is a broadly expressed calcium channel with capability to act as an integrator of
      extracellular and intracellular signals at the level of calcium entry.

PMID- 17217054
TI  - TRPC6.
AB  - TRPC6 is a Ca(2+)-permeable non-selective cation channel expressed in brain,
      smooth muscle containing tissues and kidney, as well as in immune and blood
      cells. Channel homomers heterologously expressed have a characteristic doubly
      rectifying current-voltage relationship and are six times more permeable for Ca2+
      than for Na+. In smooth muscle tissues, however, Na+ influx and activation of
      voltage-gated calcium channels by membrane depolarization rather than Ca2+
      elevation by TRPC6 channels is the driving force for contraction. TRPC6 channels
      are directly activated by the second messenger diacylglycerol (DAG) and regulated
      by specific tyrosine or serine phosphorylation. Extracellular Ca2+ has inhibitory
      effects, while Ca2+/calmodulin acting from the intracellular side has potentiator
      effects on channel activity. Given its specific expression, TRPC6 is likely to
      play a number of physiological roles. Studies with TRPC6(-/-) mice suggest a role
      for the channel in the regulation of vascular and pulmonary smooth muscle
      contraction. TRPC6 was identified as an essential component of the slit diaphragm
      architecture of kidney podocytes. Other functions in immune and blood cells, as
      well as in brain and in smooth muscle-containing tissues such as stomach, colon
      and myometrium, remain elusive.

PMID- 17217055
TI  - TRPC7.
AB  - Canonical transient receptor potential7 (TRPC7) is the seventh identified member
      of the mammalian TRPC channel family, comprising nonselective cation channels
      activated through the phospholipase C (PLC) signaling pathway. TRPC7 is directly
      activated by diacylglycerol (DAG), one of the PLC products, having high sequence
      homologywith TRPC3 and TRPC6, which are also activated by DAG. TRPC7 shows unique
      properties of activation, such as constitutive activity and susceptibility to
      negative regulation by extracellular Ca2+. Although the physiological importance
      of TRPC7 in the native environment remains elusive, TRPC7 would play important
      roles in Ca2+ signaling pathway through these characteristic features.

PMID- 17217056
TI  - Capsaicin receptor: TRPV1 a promiscuous TRP channel.
AB  - TRPV1, the archetypal member of the vanilloid TRP family, was initially
      identified as the receptor for capsaicin, the pungent ingredient in hot chili
      peppers. The receptor has a diverse tissue distribution, with high expression in
      sensory neurons. TRPV1 is a nonselective cation channel with significant
      permeability to calcium, protons, and large polyvalent cations. It is the most
      polymodal TRP channel, being activated by numerous stimuli, including heat,
      voltage, vanilloids, lipids, and protons/cations. TRPV1 acts as a molecular
      integrator of physical and chemical stimuli in peripheral nociceptor terminals
      and plays a critical role in thermal inflammatory hyperalgesia. In addition,
      TRPV1 may regulate a variety of physiological functions in different organ
      systems. Various second messenger systems regulate TRPV1 activity, predominantly
      by serine-threonine phosphorylation. In this review, we provide a concise summary
      of the information currently available about this channel.

PMID- 17217057
TI  - 2-Aminoethoxydiphenyl borate as a common activator of TRPV1, TRPV2, and TRPV3
      channels.
AB  - 2-Aminoethoxydiphenyl borate (2APB) had been depicted as a universal blocker of
      transient receptor potential (TRP) channels. While evidence has accumulated
      showing that some TRP channels are indeed inhibited by 2APB, especially in
      heterologous expression systems, there are other TRP channels that are unaffected
      or affected very little by this compound. More interestingly, the thermosensitive
      TRPV1, TRPV2, and TRPV3 channels are activated by 2APB. This has been
      demonstrated both in heterologous systems and in native tissues that express
      these channels. A number of 2APB analogs have been examined for their effects on
      native store-operated channels and heterologously expressed TRPV3. These studies
      revealed a complex mechanism of action for 2APB and its analogs on ion channels.
      In this review, we have summarized the current results on 2APB-induced activation
      of TRPV1-3 and discussed the potential mechanisms by which 2APB may regulate TRP
      channels.

PMID- 17217058
TI  - TRPV4.
AB  - TRPV4 is a non-selective cation channel subunit expressed in a wide variety of
      tissues. TRP channels are formed by a tetrameric complex of channel subunits. The
      available evidence suggests that TRPV4 cannot form heteromultimers with other
      TRPV isoforms, and that TRPV4-containing channels are homotetramers. These
      channels have a characteristic outwardly rectifying current-voltage relation, and
      are 5-10 times more permeable for Ca2+ than for Na+. TRPV4 can be activated by a
      wide range of stimuli including physical (cell swelling, heat, mechanical
      stimulation) and chemical stimuli (endocannabinoids, arachidonic acid, and,
      surprisingly, 4alpha-phorbol esters). Activation by swelling and endocannabinoids
      involves cytochrome P450 epoxygenase-dependent arachidonic acid metabolism to the
      epoxyeicosatrienoic acids (EETs). Heat and 4alpha-phorbol esters also seem to
      share a common mechanism of activation, but the endogenous messenger involved in
      the response to heat has not yet been identified. Ca2+ acting from the
      intracellular side can have both potentiating and inhibitory effects on channel
      activity and is involved in channel activation and inactivation. Given its wide
      expression and the variety of activatory stimuli, TRPV4 is likely to play a
      number of physiological roles. Studies with TRPV4(-/-) mice suggest a role for
      the channel in the regulation of body osmolarity, mechanosensation, temperature
      sensing, vascular regulation and, possibly, hearing.

PMID- 17217059
TI  - TRPV5, the gateway to Ca2+ homeostasis.
AB  - Ca2+ homeostasis in the body is tightly controlled, and is a balance between
      absorption in the intestine, excretion via the urine, and exchange from bone.
      Recently, the epithelial Ca2+ channel (TRPV5) has been identified as the gene
      responsible for the Ca2+ influx in epithelial cells of the renal distal
      convoluted tubule. TRPV5 is unique within the family of transient receptor
      potential (TRP) channels due to its high Ca2+ selectivity. Ca2+ flux through
      TRPV5 is controlled in three ways. First, TRPV5 gene expression is regulated by
      calciotropic hormones such as vitamin D3 and parathyroid hormone. Second, Ca2+
      transport through TRPV5 is controlled by modulating channel activity.
      Intracellular Ca2+, for example, regulates channel activity by feedback
      inhibition. Third, TRPV5 is controlled by mobilization of the channel through
      trafficking toward the plasma membrane. The newly identified anti-aging hormone
      Klotho regulates TRPV5 by cleaving off sugar residues from the extracellular
      domain of the protein, resulting in a prolonged expression of TRPV5 at the plasma
      membrane. Inactivation of TRPV5 in mice leads to severe hypercalciuria, which is
      compensated by increased intestinal Ca2+ absorption due to augmented vitamin D3
      levels. Furthermore, TRPV5 deficiency in mice is associated with polyuria, urine
      acidification, and reduced bone thickness. Some pharmaceutical compounds, such as
      the immunosuppressant FK506, affect the Ca2+ balance by modulating TRPV5 gene
      expression. This underlines the importance of elucidating the role of TRPV5 in
      Ca(2+)-related disorders, thereby enhancing the possibilities for pharmacological
      intervention. This chapter describes a unique TRP channel and highlights its
      regulation and function in renal Ca2+ reabsorption and overall Ca2+ homeostasis.

PMID- 17217060
TI  - TRPV6.
AB  - The ion channel TRPV6 is likely to function as an epithelial calcium channel in
      organs with high calcium transport requirements such as the intestine, kidney,
      and placenta. Transcriptional regulation of TRPV6 messenger RNA (mRNA) is
      controlled by 1,25-dihydroxyvitamin D, which is the active hormonal form of
      vitamin D3, and by additional calcium-dependent and vitamin D3-independent
      mechanisms. Under physiological conditions, the conductance of the channel itself
      is highly calcium-selective and underlies complex inactivation mechanisms
      triggered by intracellular calcium and magnesium ions. There is growing evidence
      that transcriptional regulation of TRPV6 in certain tissues undergoing malignant
      transformation, such as prostate cancer, is linked to cancer progression.

PMID- 17217061
TI  - TRPM2.
AB  - TRPM2 is a cation channel enabling influx of Na+ and Ca2+, leading to
      depolarization and increases in the cytosolic Ca2+ concentration ([Ca2+]i). It is
      widely expressed, e.g. in many neurons, blood cells and the endocrine pancreas.
      Channel gating is induced by ADP-ribose (ADPR) that binds to a Nudix box motif in
      the cytosolic C-terminus of the channel. Endogenous ADPR concentrations in
      leucocytes are sufficiently high to activate TRPM2 in the presence of an
      increased [Ca2+]i but probably not at resting [Ca2+]i. Another channel activator
      is oxidative stress, especially hydrogen peroxide (H2O2) that may act through
      ADPR after ADPR polymers have been formed by poly(ADP-ribose) polymerases (PARPs)
      and hydolysed by glycohydrolases. H2O2-stimulated TRPM2 channels essentially
      contribute to insulin secretion in pancreatic beta-cells and alloxan-induced
      diabetes mellitus. Inhibition of TRPM2 channels may be achieved by channel
      blockers such as flufenamic acid or the anti-fungal agents clotrimazole or
      econazole. Selective blockers of TRPM2 are not yet available; those would be
      valuable for a characterization of biological roles of TRPM2 in various tissues
      and as potential drugs directed against oxidative cell damage, reperfusion injury
      or leucocyte activation. Activation of TRPM2 may be prevented by anti-oxidants,
      PARP inhibitors and glycohydrolase inhibitors. In future, binding of ADPR to the
      Nudix box may be targeted. In light of the wide-spread expression and growing
      list of cellular functions of TRPM2, useful therapeutic applications are expected
      for future drugs that block TRPM2 channels or inhibit their activation.

PMID- 17217062
TI  - TRPM3.
AB  - TRPM3 is the last identified member of the TRPM subfamily and is most closely
      related to TRPM1. Due to alternative splicing, the TRPM3 gene encodes a large
      number of different variants. One splice event, affecting the pore-forming region
      of the channel, changes its selectivity for divalent cations. In this review, we
      give an overview of the identified TRPM3 variants and compare their functional
      properties.

PMID- 17217063
TI  - Insights into TRPM4 function, regulation and physiological role.
AB  - In the current review we will summarise data from the recent literature
      describing molecular and functional properties of TRPM4. Together with TRPM5,
      these channels are up till now the only molecular candidates for a class of non
      selective, Ca(2+)-impermeable cation channels which are activated by elevated
      Ca2+ levels in the cytosol. Apart from intracellular Ca2+, TRPM4 activation is
      also dependent on membrane potential. Additionally, channel activity is modulated
      by ATP, phosphatidylinositol bisphosphate (PiP2), protein kinase C (PKC)
      phosphorylation and heat. The molecular determinants for channel activation,
      permeation and modulation are increasingly being clarified, and will be discussed
      here in detail. The physiological role of Ca(2+)-activated non-selective cation
      channels is unclear, especially in the absence of gene-specific knock-out mice,
      but evidence indicates a role as a regulator of membrane potential, and thus the
      driving force for Ca2+ entry from the extracellular medium.

PMID- 17217064
TI  - TRPM5 and taste transduction.
AB  - TRPM5 is a cation channel that it is essential for transduction of bitter, sweet
      and umami tastes. Signaling of these tastes involves the activation of G protein
      coupled receptors that stimulate phospholipase C (PLC) beta2, leading to the
      breakdown of phosphatidylinositol bisphosphate (PIP2) into diacylglycerol (DAG)
      and inositol trisphosphate (IP3), and release of Ca2+ from intracellular stores.
      TRPM5 forms a nonselective cation channel that is directly activated by Ca2+ and
      it is likely to be the downstream target of this signaling cascade. Therefore,
      study of TRPM5 promises to provide insight into fundamental mechanisms of taste
      transduction. This review highlights recent work on the mechanisms of activation
      of the TRPM5 channel. The mouse TRPM5 gene encodes a protein of 1,158 amino acids
      that is proposed to have six transmembrane domains and to function as a tetramer.
      TRPM5 is structurally most closely related to the Ca(2+)-activated channel TRPM4
      and it is more distantly related to the cold-activated channel TRPM8. In patch
      clamp recordings, TRPM5 channels are activated by micromolar concentrations of
      Ca2+ and are permeable to monovalent but not divalent cations. TRPM5 channel
      activity is strongly regulated by voltage, phosphoinositides and temperature, and
      is blocked by acid pH. Study of TRPM4 and TRPM8, which show similar modes of
      regulation, has yielded insights into possible structural domains of TRPM5.
      Understanding the structural basis for TRPM5 function will ultimately allow the
      design of pharmaceuticals to enhance or interfere with taste sensations.

PMID- 17217065
TI  - TRPM6: A Janus-like protein.
AB  - TRPM6 and TRPM7 proteins share similar molecular structures and biophysical
      properties. Both proteins are Mg(2+)- and Ca(2+)-permeable cation channels with
      the typical topology of six transmembrane domains. In addition, TRPM6 and TRPM7
      function as serine/threonine kinases with kinase domains at their C-terminal
      tails. At present, the role of the association of kinase and channel domains in
      TRPM6 and TRPM7 remains elusive. TRPM6 is mainly expressed in kidney and
      intestine, where it might be responsible for epithelial Mg2+ re/absorption. This
      hypothesis is strengthened by the identification of TRPM6 mutants in patients
      with a rare but severe hereditary disease called hypomagnesaemia with secondary
      hypocalcaemia. The aim of this review is to provide a brief but concise overview
      of the information currently available about TRPM6.

PMID- 17217066
TI  - The Mg2+ and Mg(2+)-nucleotide-regulated channel-kinase TRPM7.
AB  - TRPM7 is a member of the melastatin-related subfamily of TRP channels and
      represents a protein that contains both an ion channel and a kinase domain. The
      protein is ubiquitously expressed and represents the only ion channel known that
      is essential for cellular viability. TRPM7 is a divalent cation-selective ion
      channel that is permeable to Ca2+ and Mg2+, but also conducts essential metals
      such as Zn2+, Mn2+, and Co2+, as well as nonphysiologic or toxic metals such as
      Ni2+, Cd2+, Ba2+, and Sr2+. The channel is constitutively open but strongly
      downregulated by intracellular levels of Mg2+ and MgATP and other Mg-nucleotides.
      Reducing the cellular levels of these regulators leads to activation of TRPM7
      mediated currents that exhibit a characteristic nonlinear current-voltage
      relationship with pronounced outward rectification due to divalent influx at
      physiologically negative voltages and monovalent outward fluxes at positive
      voltages. TRPM7 channel activity is also actively regulated following receptor
      mediated changes in cyclic AMP (cAMP) and protein kinase A activity. This
      regulation as well as that by Mg-nucleotides requires a functional endogenous
      kinase domain. The function of the kinase domain is not completely understood,
      but may involve autophosphorylation of TRPM7 as well as phosphorylation of other
      target proteins such as annexin and myosin IIA heavy chain. Based on these
      properties, TRPM7 is currently believed to represent a ubiquitous homeostatic
      mechanism that regulates Ca2+ and Mg2+ fluxes based on the metabolic state of the
      cell. Physiologically, the channel may serve as a regulated transport mechanism
      for these ions that could affect cell adhesion, cell growth and proliferation,
      and even cell death under pathological stress such as anoxia.

PMID- 17217067
TI  - TRPM8.
AB  - Originally cloned as a prostate-specific protein, TRPM8 is now best known as a
      cold- and menthol-activated channel implicated in thermosensation. In this
      chapter we provide a brief review of current knowledge concerning the biophysical
      properties, gating mechanisms, pharmacology and (patho)physiology of this TRP
      channel.

PMID- 17217068
TI  - TRPA1.
AB  - The TRPA1 protein has up to 18 N-terminal and presumed cytoplasmic ankyrin
      repeats followed by the six membrane spanning and single pore-loop domains
      characteristic of all TRPs. In mice, TRPA1 is almost exclusively expressed in
      nociceptive neurons of peripheral ganglia and in all the mechanosensory epithelia
      of inner ear. In nociceptive neurons, TRPA1 mediates the response to the
      proalgesic bradykinin as well as the response to pungent irritants found in
      mustards and garlic, and probably also to those found in cinnamon and tear gas.
      The channel properties of TRPA1 are discussed and compared to those of sensory
      transducers. TRPA1 is well conserved across the animal kingdom, with likely
      orthologs from human to nematode, which suggest an ancestral role for this
      channel, probably in sensation.

PMID- 17217069
TI  - TRPP2 channel regulation.
AB  - Polycystin-2, or TRPP2 according to the TRP nomenclature, is encoded by PKD2, a
      gene mutated in patients with autosomal-dominant polycystic kidney disease. Its
      precise subcellular location and its intracellular trafficking are a matter of
      intense debate, although consensus has emerged that it is located in primary
      cilia, a long-neglected organelle possibly involved in sensory functions.
      Polycystin-2 has a calculated molecular mass of 110 kDa, and according to
      structural predictions it contains six membrane-spanning domains and a pore
      forming region between the 5th and 6th membrane-spanning domain. This section
      irst introduces the reader to the field of cystic kidney diseases and to the PKD2
      gene, before the ion channel properties of polycystin-2 are discussed in great
      detail.

PMID- 17217070
TI  - TRP channels of the pancreatic beta cell.
AB  - Orchestrated ion fluctuations within pancreatic islets regulate hormone secretion
      and maybe essential to processes such as apoptosis. A diverse set of ion channels
      allows for islet cells to respond to a variety of signals and dynamically
      regulate hormone secretion and glucose homeostasis (reviewed by Houamed et al.
      2004). This chapter focuses on transient receptor potential (TRP)-related
      channels found within the beta cells of the islet and reviews their roles in both
      insulin secretion and apoptosis.

PMID- 17217071
TI  - TRP channels in platelet function.
AB  - Ca2+ entry forms an essential component of platelet activation; however, the
      mechanisms associated with this process are not understood. Ca2+ entry upon
      receptor activation occurs as a consequence of intracellular store depletion
      (referred to as store-operated Ca2+ entry or SOCE), a direct action of second
      messengers on cation entry channels or the direct occupancy of a ligand-gated
      P2(Xi) receptor. The molecular identity of the SOCE channel has yet to be
      established. Transient receptor potential (TRP) proteins are candidate cation
      entry channels and are classified into a number of closely related subfamilies
      including TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP
      (polycystin) and TRPML (mucolipins). From the TRPC family, platelets have been
      shown to express TRPC6 and TRPC1, and are likely to express other TRPC and other
      TRP members. TRPC6 is suggested to be involved with receptor-activated, diacyl
      glycerol-mediated cation entry. TRPC1 has been suggested to be involved with
      SOCE, though many of the suggested mechanisms remain controversial. As no single
      TRP channel has the properties described for SOCE in platelets, it is likely that
      it is composed of a heteromeric association of TRP and related subunits, some of
      which may be present in intracellular compartments in the resting cell.

PMID- 17217072
TI  - TRP channels in lymphocytes.
AB  - TRP proteins form ion channels that are activated following receptor stimulation.
      Several members of the TRP family are likely to be expressed in lymphocytes.
      However, in many studies, messenger RNA (mRNA) but not protein expression was
      analyzed and cell lines but not primary human or murine lymphocytes were used.
      Among the expressed TRP mRNAs are TRPC1, TRPC3, TRPM2, TRPM4, TRPM7, TRPV1, and
      TRPV2. Regulation of Ca2+ entry is a key process for lymphocyte activation, and
      TRP channels may both increase Ca2+ influx (such as TRPC3) or decrease Ca2+
      influx through membrane depolarization (such as TRPM4). In the future, linking
      endogenous Ca2+/cation channels in lymphocytes with TRP proteins should lead to a
      better molecular understanding of lymphocyte activation.

PMID- 17217073
TI  - Link between TRPV channels and mast cell function.
AB  - Mast cells are tissue-resident immune effector cells. They respond to diverse
      stimuli by releasing potent biological mediators into the surrounding tissue, and
      initiating inflammatory responses that promote wound healing and infection
      clearance. In addition to stimulation via immunological routes, mast cells also
      respond to polybasic secretagogues and physical stimuli. Each mechanism for mast
      cell activation relies on the influx of calcium through specific ion channels in
      the plasma membrane. Recent reports suggest that several calcium-permeant cation
      channels of the TRPV family are expressed in mast cells. TRPV channels are a
      family of sensors that receive and react to chemical messengers and physical
      environmental cues, including thermal, osmotic, and mechanical stimuli. The
      central premise of this review is that TRPVs transduce physiological and
      pathophysiological cues that are functionally coupled to calcium signaling and
      mediator release in mast cells. Inappropriate mast cell activation is at the core
      of numerous inflammatory pathologies, rendering the mast cell TRPV channels
      potentially important therapeutic targets.

PMID- 17217074
TI  - TRPV channels' role in osmotransduction and mechanotransduction.
AB  - In signal transduction of metazoan cells, transient receptor potential (TRP) ion
      channels have been identified that respond to diverse external and internal
      stimuli, among them osmotic and mechanical stimuli. This chapter will summarize
      findings on the TRPV subfamily, both its vertebrate and invertebrate members. Of
      the six mammalian TRPV channels, TRPV1, -V2, and -V4 were demonstrated to
      function in transduction of osmotic and/or mechanical stimuli. TRPV channels have
      been found to function in cellular as well as systemic osmotic homeostasis in
      vertebrates. Invertebrate TRPV channels, five in Caenorhabditis elegans and two
      in Drosophila, have been shown to play a role in mechanosensation, such as
      hearing and proprioception in Drosophila and nose touch in C. elegans, and in the
      response to osmotic stimuli in C. elegans. In a striking example of evolutionary
      conservation of function, mammalian TRPV4 has been found to rescue mechanosensory
      and osmosensory deficits of the TRPV mutant line osm-9 in C. elegans, despite no
      more than 26% orthology of the respective amino acid sequences.

PMID- 17217075
TI  - Nociception and TRP channels.
AB  - Pain is initiated when noxious stimuli excite the peripheral terminals of
      specialized primary afferent neurons called nociceptors. Many molecules are
      involved in conversion of the noxious stimuli to the electrical signals in the
      nociceptor endings. Among them, TRP channels play important roles in detecting
      noxious stimuli.

PMID- 17217076
TI  - Regulation of TRP ion channels by phosphatidylinositol-4,5-bisphosphate.
AB  - Phosphatidylinositol-4,5-bisphosphate (PIP2) has emerged as a versatile regulator
      of TRP ion channels. In many cases, the regulation involves interactions of
      channel proteins with the lipid itself independent of its hydrolysis products.
      The functions of the regulation mediated by such interactions are diverse. Some
      TRP channels absolutely require PIP2 for functioning, while others are inhibited.
      A change of gating is common to all, endowing the lipid a role for modulation of
      the sensitivity of the channels to their physiological stimuli. The activation of
      TRP channels may also influence cellular PIP2 levels via the influx of Ca2+
      through these channels. Depletion of PIP2 in the plasma membrane occurs upon
      activation of TRPV1, TRPM8, and possibly TRPM4/5 in heterologous expression
      systems, whereas resynthesis of PIP2 requires Ca2+ entry through the TRP/TRPL
      channels in Drosophila photoreceptors. These developments concerning PIP2
      regulation of TRP channels reinforce the significance of the PLC signaling
      cascade in TRP channel function, and provide further perspectives for
      understanding the physiological roles of these ubiquitous and often enigmatic
      channels.

PMID- 17217077
TI  - TRPC, cGMP-dependent protein kinases and cytosolic Ca2+.
AB  - Ca2+, nitric oxide (NO), and protein kinase G (PKG) are important signaling
      molecules that play pivotal roles in many physiological processes such as
      vascular tone control, platelet activation, and synaptic plasticity. TRPC
      channels allow Ca2+ influx, thus contributing to the production of NO, which
      subsequently stimulates PKG. It has been demonstrated that PKG can phosphorylate
      human TRPC3 at Thr-11 and Ser-263 and that this phosphorylation inactivates
      TRPC3. These two PKG phosphorylation sites, Thr-11 and Ser-263 in human TRPC3,
      are conserved in other members of the TRPC3/6/7 subfamily, suggesting that PKG
      may also phosphorylate TRPC6 and TRPC7. In addition, protein kinase C (PKC) also
      inactivates TRPC3, partly through activating PKG. The PKG-mediated inhibition of
      TRPC channels may provide a feedback control for the fine tuning of [Ca2+]i
      levels and protect the cells from the detrimental effects of excessive [Ca2+]i
      and/or NO.

PMID- 17217078
TI  - Trafficking of TRP channels: determinants of channel function.
AB  - Transient receptor potential (TRP) channels are members of a relatively newly
      described family of cation channels that display a wide range of properties and
      mechanisms of activation. The exact physiological function and regulation of most
      of these channels have not yet been conclusively determined. Studies over the
      past decade have revealed important features of the channels that contribute to
      their function. These include homomeric interactions between TRP monomers,
      selective heteromeric interactions within members of the same subfamily,
      interactions of TRPs with accessory proteins and assembly into macromolecular
      signaling complexes, and regulation within functionally distinct cellular
      microdomains. Further, distinct constitutive and regulated vesicular trafficking
      mechanisms have a critical role not only in controlling the surface expression of
      TRP channels but also their activation in response to stimuli. A number of
      cellular components such as cytoskeletal and scaffolding proteins also contribute
      to TRP channel trafficking. Thus, mechanisms involved in the assembly and
      trafficking of TRP channels control their plasma membrane expression and
      critically impact their function and regulation.

PMID- 17217079
TI  - TRPC channels: interacting proteins.
AB  - TRP channels, in particular the TRPC and TRPV subfamilies, have emerged as
      important constituents of the receptor-activated Ca2+ influx mechanism triggered
      by hormones, growth factors, and neurotransmitters through activation
      ofphospholipase C (PLC). Several TRPC channels are also activated by passive
      depletion of endoplasmic reticulum (ER) Ca2+. Although in several studies the
      native TRP channels faithfully reproduce the respective recombinant channels,
      more often the properties of Ca2+ entry and/or the store-operated current are
      strikingly different from that of the TRP channels expressed in the same cells.
      The present review aims to discuss this disparity in the context of interaction
      of TRPC channels with auxiliary proteins that may alter the permeation and
      regulation of TRPC channels.

PMID- 17217080
TI  - TRPC channels: integrators of multiple cellular signals.
AB  - TRPC channels are ubiquitously expressed among cell types and mediate signals in
      response to phospholipase C (PLC)-coupled receptors. TRPC channels function as
      integrators of multiple signals resulting from receptor-induced PLC activation,
      which catalyzes the breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) to
      produce inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3
      depletes Ca2+ stores and TRPC3 channels can be activated by store-depletion.
      InsP3 also activates the InsP3 receptor, which may undergo direct interactions
      with the TRPC3 channel, perhaps mediating store-dependence. The other PLC
      product, DAG, has a direct non-PKC-dependent activating role on TRPC3 channels
      likely by direct binding. DAG also has profound effects on the TRPC3 channel
      through PKC. Thus PKC is a powerful inhibitor of most TRPC channels and DAG is a
      dual regulator of the TRPC3 channel. PLC-mediated DAG results in rapid channel
      opening followed later by a slower DAG-induced PKC-mediated deactivation of the
      channel. The decreased level of PIP2 from PLC activation also has an important
      modifying action on TRPC3 channels. Thus, the TRPC3 channel and PLCgamma form an
      intermolecular PH domain that has high specificity for binding PIP2. This
      interaction allows the channel to be retained within the plasma membrane, a
      further operational control factor for TRPC3. As nonselective cation channels,
      TRPC channel opening results in the entry of both Na+ and Ca2+ ions. Thus, while
      they may mediate Ca2+ entry signals, TRPC channels are also powerful modifiers of
      membrane potential.

PMID- 17217081
TI  - Phospholipase C-coupled receptors and activation of TRPC channels.
AB  - The canonical transient receptor potential (TRPC) cation channels are mammalian
      homologs of the photoreceptor channel TRP in Drosophila melanogaster. All seven
      TRPCs (TRPC1 through TRPC7) can be activated through Gq/11 receptors or receptor
      tyrosine kinase (RTK) by mechanisms downstream of phospholipase C. The last
      decade saw a rapidly growing interest in understanding the role of TRPC channels
      in calcium entry pathways as well as in understanding the signal(s) responsible
      for TRPC activation. TRPC channels have been proposed to be activated by a
      variety of signals including store depletion, membrane lipids, and vesicular
      insertion into the plasma membrane. Here we discuss recent developments in the
      mode of activation as well as the pharmacological and electrophysiological
      properties of this important and ubiquitous family of cation channels.

PMID- 17217082
TI  - Antibiotic use in swine farms in Alberta.

PMID- 17217083
TI  - Veterinary care for animals owned by those who cannot afford to pay.

PMID- 17217084
TI  - An ethicist's commentary on soliciting client contributions to a fund raiser.

PMID- 17217085
TI  - Problematic client-animal relationships: Munchausen by proxy.

PMID- 17217086
TI  - Pharmacogenetics: it's not just about ivermectin in collies.

PMID- 17217087
TI  - Cryptosporidium spp. and other zoonotic enteric parasites in a sample of domestic
      dogs and cats in the Niagara region of Ontario.
AB  - To determine the prevalence of Cryptosporidium spp. and other zoonotic enteric
      parasites in a sample of domestic dogs and cats in the Niagara region, Ontario, 5
      of 26 clinics invited by mail survey reported their parasitological findings over
      24 months. Stool samples collected by 1 clinic over 68 days were investigated for
      parasites by using several techniques (fecal concentration, acid-fast staining,
      and a Cryptosporidium immunoassay). The 5 clinics that provided data indicated
      Toxocara spp. as the most frequent finding. Parasitological study of 111 stool
      samples showed a high overall positivity rate in samples from both dogs (40%) and
      cats (36.6%). Cryptosporidium spp. antigen was detected in 7.4% and 7.3%,
      Toxocara spp. in 14.2% and 12.2%, and Giardia spp. 7.1% and 2.4% of dog and cat
      samples, respectively. The high prevalence of zoonotic parasites in the Niagara
      region is important, and increased awareness of their potential threat to human
      health is necessary. Additionally, further research into the zoonotic capacity of
      Cryptosporidium spp. and Giardia spp. is necessary.

PMID- 17217088
TI  - Retrospective investigation of chronic wasting disease of cervids at the Toronto
      Zoo, 1973-2003.
AB  - The occurrence of chronic wasting disease (CWD) at the Toronto Zoo was
      investigated retrospectively, based on an examination of management, animal
      health, and postmortem records, and immunohistochemical studies. Records of
      animal movements, clinical signs, and postmortem findings were examined for all
      cervids 1973-2003. All available samples of fixed, wax-embedded lymphoid or
      central nervous system tissue from cervids that died at the Toronto Zoo from 1973
      to 2003, > 12 months of age, were tested, using prion protein immunostaining.
      Chronic wasting disease prion antigen was detected in 8 of 105 animals tested: 7
      mule deer and 1 black-tailed deer. The most likely method of introduction was the
      importation of CWD-infected animals from a zoo in the United States. Animal-to
      animal contact and environmental contamination were the most likely methods of
      spread of CWD at the zoo. No mule deer left the Toronto Zoo site, and the last
      animal with CWD died in 1981. Historic findings and ongoing testing of cervids
      indicate that the Toronto Zoo collection has very low risk of currently being
      infected with CWD.

PMID- 17217089
TI  - The low seroprevalence of tick-transmitted agents of disease in dogs from
      southern Ontario and Quebec.
AB  - Infectious diseases caused by pathogens transmitted by ticks and other insect
      vectors are an important cause of morbidity and mortality in both dogs and humans
      throughout North America. The purpose of this study was to determine the
      seroprevalence of selected vector-transmitted pathogens in southern Ontario and
      Quebec. Samples submitted to the Vector Borne Disease Diagnostic Laboratory
      (VBDDL) at the North Carolina State University College of Veterinary Medicine
      were evaluated for antibodies to Ehrlichia canis, Anaplasma phagocytophilum,
      Babesia canis, Bartonella henselae, Borrelia burgdorferi, Bartonella vinsonii
      subspecies berkhoffii, and Rickettsia rickettsii. Information regarding breed and
      the city or province from which the sample originated was recorded; however,
      travel history was unknown for the majority of dogs. Overall seroprevalence to
      these tick-borne pathogens in southern Ontario and Quebec is low compared with
      most regions of the United States, suggesting that veterinarians in this region
      of Canada should pursue diagnostic evidence of infection in dogs with a travel
      history or prior residence in areas endemic for exposure to tick-borne
      infections.

PMID- 17217090
TI  - Outbreak of Salmonella Dublin-associated abortion in Danish fur farms.
AB  - Outbreaks of Salmonella Dublin infections were recorded in 25 Danish mink and fox
      farms. All farms suffered extensive disease problems; clinical and pathological
      observations included abortion, stillbirths, necrotizing endometritis, and
      increased mortality. By genotyping with pulsed-field gel electrophoresis and
      amplified fragment length polymorphism, all isolates of S. Dublin had
      indistinguishable patterns. The outbreaks took place during April and May, around
      the time of whelping. During this period, mink are particularly susceptible to
      Salmonella infections. All affected farms were served by the same feed factory
      and it was concluded that a batch of contaminated feed was responsible for the
      outbreaks, although repeated culture of feed samples collected during the same
      period were negative. No other likely source could be identified. The results
      emphasize the importance of strict hygiene measures at feed factories and the
      proper use of ingredients of known Salmonella status, in particular during the
      whelping season. Infected mink farms did not have a higher risk of outbreak of
      salmonellosis in the year following the outbreak.

PMID- 17217091
TI  - Horner's syndrome associated with parotid duct obstruction in a sheep.
AB  - A 9-year old, Rasa Aragonesa ewe was presented with a left-sided, facial, soft
      fluctuant swelling. The postmortem examination showed grass awns filling the
      entire length of the parotid gland duct. The presence of parotid duct obstruction
      with Horner's syndrome, previously unreported in sheep, is discussed.

PMID- 17217092
TI  - Surgical repair of traumatic oronasal fistula in a domestic short-haired cat.
AB  - A 9-month-old, spayed female domestic shorthair was presented with a suspected
      traumatic oronasal fistula. Two surgical attempts using mucosal advancement flaps
      and single layer closure failed, likely due to inadequate blood supply that was
      potentially exacerbated by excess tension and trauma on the graft.

PMID- 17217093
TI  - Veterinary diagnostic imaging. Chronic pancreatitis resulting in marked
      infiltrative fibrosis and necrosis.

PMID- 17217094
TI  - Ruptures of the common calcaneal tendon.

PMID- 17217095
TI  - [The frequencies of apolipoprotein E genotypes in health and disease in the
      Croatian population--an overview of expectations and real results].
AB  - The aim of the overview is to show the distribution of common apolipoprotein E
      (APOE) genotypes in the Croatian population, and to test whether it could serve
      as a new molecular biomarker in some clinical entities. The study included the
      following groups: patients with angiographically confirmed coronary artery
      disease, myocardial infarction, Alzheimer's dementia, vascular dementia,
      hyperlipidemias, diabetes mellitus, pancreatitis, and healthy subjects. Group
      comparisons of different clinical entities and control group were performed using
      Pearson's Chi2-test. There was no difference in APOE genotype frequencies between
      coronary artery disease neither myocardial infarction and control group. The ApoE
      genotype frequencies in patients with Alzheimer's disease were significantly
      different from those in the control group. APOE-4 allele tends to be a risk
      factor for the development of Alzheimer's disease. The frequencies were only
      marginally different in vascular dementia. Patients with hypercholesterolemia,
      those with inherited familial hypercholesterolemia, children with diabetes
      mellitus, and patients with pancreatitis of different etiology showed
      distributions of APOE genotypes that differed from the control group. It is
      concluded that the frequencies of APOE genotypes yielded no statistically
      significant result to confirm the association between APOE genotypes and any
      specific disease with the exception of Alzheimer's disease; APO-epsilon4 allell
      has become one of the important biomarkers in diagnosis of Alzheimer's dementia.

PMID- 17217096
TI  - [Human anaplasmosis (ehrlichiosis)].
AB  - OBJECTIVE: The north part of Croatia, especially the Koprivnica-Krizevci County
      is a well known endemic area of several tick-transmitted diseases including tick
      borne encephalitis, Lyme borreliosis and tularemia. Each summer numerous patients
      develop a nonspecific febrile illness after tick bite, etiology of which is
      sometimes never established. PURPOSE OF WORK: The aim of this prospective study
      was to determine whether the infection with Anaplasma phagocytophilum was
      associated with febrile illnesses occurring after tick bite. The epidemiological,
      clinical and laboratory characteristics, and diagnostic procedures in patients
      suffering from confirmed and probable anaplasmosis are presented. PATIENTS AND
      METHODS: A prospective study to assess the potential ehrlichial etiology of
      febrile illnesses after tick bite was conducted at the Department of Infectious
      Disease, General Hospital, Koprivnica, Croatia, during the period from January
      1998 to August 2004. The study included patients of all age groups with acute
      febrile illness (temperature higher than 38 degrees C) manifesting within 30 days
      of a tick bite, in whom a recent infection with Anaplasma phagocytophilum was
      established serologically by seroconversion or at least 4-fold increase in
      antibody titer to anaplasma antigen (defined as confirmed cases of anaplasmosis),
      or by the presence of positive IFA titer > or = 1: 256 in acute and convalescent
      phase serum samples without demonstrating a 4-fold titer change (defined as
      probable cases of anaplasmosis), and with no alternative explanation for the
      acute febrile illness. Thorough medical histories were collected, physical
      examinations performed, and several laboratory tests carried out. Giemsa-stained
      peripheral blood smears were examined by high microscopy for the presence of
      ehrlichial morulae within leukocytes. Acute and convalescent phase serum samples
      were tested by use of an indirect immunofluorescence assay (IFA) for the presence
      of specific IgG antibodies to Anaplasma phagocytophilum antigen. At the same time
      all serum samples were tested for other tick borne agents including tick-borne
      encephalitis virus, Borrelia burgdorferi sensu lato and Ehrlichia chaffeensis.
      Serological tests were performed at the Institute of Microbiology and Immunology,
      School of Medicine, University of Ljubljana, Ljubljana, Slovenia. Oral consent
      was obtained from all patients enrolled in the study. RESULTS: Of 132 patients
      included in the study during the 7-year period, eight (6%) patients were
      diagnosed with anaplasmosis, without any additional diagnosis, and were included
      in the analysis. Three patients fulfilled the case definition criteria for
      confirmed anaplasmosis, while five had probable anaplasmosis (three men and five
      women aged 17-43). Clinically, the disease presented as a nonspecific, flu-like
      febrile illness with leukopenia, thrombocytopenia and moderately elevated
      aminotransferases. Intracytoplasmic morulae were not seen in leukocytes in blood
      smears. Specific antimicrobial therapy was administered in four patients. All
      patients recovered rapidly and no long-term consequences were found during the
      one-year follow-up. CONCLUSION: We report on the first patients meeting the case
      definition criteria for confirmed and probable anaplasmosis. The frequency and
      new concepts in the disease were analyzed.

PMID- 17217097
TI  - [Comparison of different methods for the detection of enteroviruses in drinking
      water].
AB  - Detection of enteroviruses in drinking water poses a very specific problem, since
      a very small number of particles have to be identified in huge water quantities.
      Currently, there are a number of methods to identify the concentration of virus
      particles and RNA templates to carry out RT-PCR, however, no standard method has
      yet been proposed. AIM: The aim of this report is to suggest optimal methods for
      the preparation of RNA templates to carry out RT-PCR. MATERIAL AND METHODS: In
      this experimental study, two different methods were employed on preparing RNA
      template. The concentration of virus particles in a large (10 L) and small (1 L)
      quantity of water was determined by use of the electropositive microporous
      virology filter (method 1 and method 2). Elution and flocculation of the virals
      particles were performed by organic extraction (method 1) and inorganic
      extraction (method 2). The sensitivity of the methods was assessed by testing the
      artificially contaminated water with 10(1) to 10(5) virus-particles using 1-L and
      10-L containers of water. RESULTS: Method 1 detected 10(5) and 10(4) virus
      particles, method 2 10(5), 10(4) and 10(3) virus particles from 10 L and 1 L of
      water, respectively, yielding a statistically significant difference (p<0.01;
      chi2 = 6.061). Using two-step RT-PCR with nested PCR method, enteroviruses were
      detected in 42/100 (42%) samples of surface drinking water and in 83% of the same
      samples using RT-PCR without nested PCR.

PMID- 17217098
TI  - [Inflammatory indicators in patients after surgery of the large intestine].
AB  - BACKGROUND AND AIMS: Despite recent advances in surgical techniques and intensive
      care management, infectious complications and sepsis remain significant problem
      after abdominal surgery. Therefore, inflammatory parameters were looked for that
      could help achieve an early and more reliable diagnosis of postoperative
      infections. C-reactive protein (CRP) is a nonspecific inflammatory mediator which
      is significantly increased postoperatively, regardless of the type of operation
      and the presence or absence of complications. Procalcitonin (PCT), the prohormone
      of calcitonin, referred to as a marker of sepsis, is increased significantly in
      severe bacterial and fungal infections. Quantitative PCT measurements in surgical
      patients have shown that postoperative PCT concentrations depend on the type and
      extent of surgery. PCT increased most after major abdominal surgery, although PCT
      concentrations were significantly higher in patients with complications compared
      to patients with uneventful postoperative course. The aim of the study was to
      determine PCT concentrations with a rapid semiquantitative PCT-Q test in the
      early postoperative period after colon surgery and to investigate its potential
      use in the diagnosis of infectious complications compared to CRP. METHODS: Thirty
      eight adult patients undergoing elective surgery of the intestine were followed
      up. None of the patients had clinical or laboratory signs of infection
      preoperatively. Leukocytes, CRP and PCT were determined preoperatively and on
      postoperative days 1-3 and 5. PCT was measured with the B. R. A. H. M. S PCT-Q
      semiquantitative test. CRP and PCT measurements in 30 patients with normal
      recovery were statistically analyzed. RESULTS: CRP was significantly elevated
      postoperatively in all patients at the 4 time points with maximum values on
      postoperative day 2. There was no difference in CRP values between patients with
      and without complications. Although PCT concentration was increased in 15 of 30
      patients with normal recovery, only mild increase (>0.5-2 ng/L) was recorded in
      13, and moderate increase (>2-10 ng/L) in only two patients. PCT increase was
      most frequently found on postoperative day 1 or 2, and more rarely on
      postoperative day 3. The number of patients with elevated PCT was significantly
      higher (8 of 8 patients) in the group with complications, which included
      postoperative infections in 7 of 8 patients, than in the group without
      complications. CONCLUSION: In the early postoperative period after major
      abdominal surgery, CRP is invariably increased and cannot help in recognizing
      infectious complications. In our study, which included a relatively small number
      of patients after colon surgery, PCT >2 ng/mL, as measured with semiquantitative
      PCT-Q test on postoperative days 1-5, or >0.5 ng/ml after postoperative day 3,
      was rarely recorded in patients with normal postoperative course. We conclude
      that PCT-Q test can be helpful in the early diagnosis of infectious complications
      after abdominal surgery.

PMID- 17217099
TI  - [Specific characteristics of hypertension in postmenopausal women].
AB  - Sex-specific differences in the incidence of cardiovascular diseases have long
      been known, and estrogens have been considered responsible for this
      dissimilarity. After the menopause, the consequences of hypertension in women
      change. Their risks of myocardial infarction and stroke rise, which has in part
      been ascribed to the loss of estrogen and onset of menopausal metabolic syndrome.
      Sex differences in the components of the renin-angiotensin system have been shown
      to exist, and may play a central role in the blood pressure control. Hypertensive
      menopausal women do not receive optimal treatment. They have poorer prognosis
      than men of the same age. Therefore, their antihypertensive management calls for
      special attention.

PMID- 17217100
TI  - [Acute risk factors for the onset of acute coronary syndromes].
AB  - Acute coronary syndrome (ACS) is an important entity of the cardiovascular
      morbidity and mortality. Everyday circumstances which significantly increase the
      risk of the onset of ACS during the period of several hours have been termed
      acute risk factors. This term includes morning hours and various possible
      external triggers such as heavy physical exertion, emotional stress, sexual
      activity, meteorological stress, and large meals. Possible external triggers
      precede approximately a half of the onsets of ACS, more frequently in men.
      Conversely, emotional stress plays a more important role in the triggering of ACS
      in women. Circadian rhythm represents an independent natural pattern of
      endogenous functions which is responsible for the morning excess in the incidence
      of ACS. A beneficial effect of regular physical activity and use of beta-blocker,
      calcium antagonists, nitrates and aspirin in the prevention of triggering ACS by
      acute risk factors has been described. Identification of further acute risk
      factors and better understanding of internal triggering mechanisms may improve
      the prevention of ACS and other cardiovascular incidents.

PMID- 17217101
TI  - [Regulatory T cells].
AB  - Regulatory T-cells are a subset of T cells that have beene extensively studied in
      modern immunology. They are important for the maintenance of peripheral
      tolerance, and have an important role in various clinical conditions such as
      allergy, autoimmune disorders, tumors, infections, and in transplant medicine.
      Basically, this population has a suppressive effect on the neighboring immune
      cells, thus contributing to the local modulation and control of immune response.
      There are two main populations of regulatory T cells - natural regulatory T
      cells, which form a distinct cellular lineage, develop in thymus and perform
      their modulatory action through direct intercellular contact, along with the
      secreted cytokines; and inducible regulatory T cells, which develop in the
      periphery after contact with the antigen that is presented on the antigen
      presenting cell, and their primary mode of action is through the interleukin 10
      (IL-10) and transforming growth factor beta (TGF-alpha) cytokines. Natural
      regulatory T cells are activated through T cell receptor after contact with
      specific antigen and inhibit proliferation of other T cells in an antigen
      independent manner. One of the major difficulties in the research of regulatory T
      cells is the lack of specific molecular markers that would identify these cells.
      Natural regulatory T cells constitutively express surface molecule CD25, but many
      other surface and intracellular molecules (HLA-DR, CD122, CD45RO, CD62, CTLA-4,
      GITR, PD-1, Notch, FOXP3, etc.) are being investigated for further phenotypic
      characterization of these cells. Because regulatory T cells have an important
      role in establishing peripheral tolerance, their importance is manifested in a
      number of clinical conditions. In the IPEX syndrome (immunodysregulation,
      polyendocrinopathy and enteropathy, X-linked), which is caused by mutation in
      Foxp3 gene that influences the development and function of regulatory T cells,
      patients develop severe autoimmune reactions that involve autoimmune endocrine
      disorders (type 1 diabetes, thyroiditis), respiratory and nutritive allergy,
      eczema and severe infections. In different types of allergy (pollen allergy, dust
      mite, nutritive allergens, contact hypersensitivity, etc.) and autoimmune
      diseases (such as rheumatoid arthritis, multiple sclerosis and type 1 diabetes) a
      lower number or decreased functional capability of regulatory T cells have been
      described. In inflammatory conditions and infections, this cell population has an
      important task in restricting immune response and protecting the host from
      excessive damage. This ability of regulatory T cells can be used by some
      pathogens (Epstein Barr virus, Mycobacterium tuberculosis, Leishmania major,
      etc.) and tumor cells to avoid host response and therefore contribute to the
      development of some pathological conditions. The knowledge gained on the
      phenotype and function of regulatory T cells could be useful in many medical
      conditions. In allergy, autoimmune diseases and in transplant procedures in
      medicine it would be desirable to increase their function, thus to partially
      suppress the immune system activity. On the other hand, in some infections and
      tumors, it would be preferable to decrease the activity of regulatory T cells and
      boost the function of effector T cells. Regulatory T cells comprise a very active
      field of immunology, therefore monitoring and modulating of their activity is of
      great potential significance in a broad spectrum of clinical conditions. By
      developing and standardizing methods for their monitoring, it would be possible
      to follow additional parameters of certain clinical conditions and possibly
      utilize them in therapy.

PMID- 17217102
TI  - [Principles of iron therapy in hemodialysis patients].
AB  - Anemia associated with chronic renal disease remains a major concern for
      nephrologists as it significantly increases the morbidity and mortality in this
      patient group. The introduction of erythropoietin has dramatically changed the
      treatment of anemia in uremic patients. However, some patients showed
      hyporesponsiveness to erythropoietin because of inadequate iron supply to the
      erythroid bone marrow. Patients undergoing chronic intermittent hemodialysis are
      especially vulnerable to iron deficiency due to blood loss during the
      hemodiaylsis sessions, gastrointestinal bleeding and compromised gastrointestinal
      absorption. Demand for iron is also increased by the treatment for anemia with
      erythropoietin. Intravenous administration is more effective than oral iron
      supplemantation in renal failure patients. Some studies have raised concerns of
      the potential serious side effects associated with intravenous iron
      administration. Besides anaphylactic reactions that were reported to occur in
      less than 1% of patients treated with iron dextran and have not been associated
      with other iron formulations, concerns about the long-term use of iron include
      the increased risk of infections and oxidative stress with consequent
      cardiovascular disease. Therapy with dextran-free iron formulations is an
      essential part of anemia treatment protocols, and was not found to be associated
      with either short- or long-term serious side effects.

PMID- 17217103
TI  - [Medical informatics education at medical schools in Bosnia and Herzegovina].
AB  - AIM: Standardization of education process and almost every aspect of life in EU
      moved the authors of this paper to evaluate medical informatics education at
      medical schools in Bosnia and Herzegovina. A very complex political structure and
      existence of two entities, one district and ten cantons in the Federation of
      Bosnia and Herzegovina caused great differences in the curricula, teaching
      methods and quality of acquired knowledge among medical schools in the country.
      Also, on the example of the teaching process at the Medical School, University of
      Sarajevo, the authors propose a future united and integrated system in the area.
      METHOD: Method of the study is descriptive, comparing education in medical
      informatics at five B&H medical schools. Over 500 students answered
      questionnaires designed at medical schools in Sarajevo and Tuzla. The questions
      tackled the contents of the subject of medical informatics, the possibility of
      acquiring knowledge from both practical and theoretic lessons, "good" and "bad"
      sides of the curricula as well as students' computer literacy. RESULTS: The
      subject of medical informatics is being taught in at least 3-4 different ways.
      Medical schools in Banja Luka and Foca/Srbinje are under a strong influence of
      the University of Belgrade, Serbia and Montenegro; the teaching staff in Mostar
      are from Croatia; the University of Tuzla has its own way; and Medical School in
      Sarajevo maintains high quality values and principles. Things and events that
      distinguish the Medical School, University of Sarajevo is the fact that it is the
      only medical school in Bosnia and Herzegovina which has a web site of of the
      Department of Medical Informatics, organized a number of events including a
      distance learning course, and has a highly competent teaching staff. Medical
      School in Sarajevo is the oldest medical school in Bosnia and Herzegovina
      established in 1944. As a required subject, medical informatics was introduced in
      the academic year 1992/1993, and it is the only medical school in Bosnia and
      Herzegovina where medical informatics is taught in two semesters, second and
      eleventh. DISCUSSION: Three important areas are discussed: the quality of
      education in secondary schools should be improved; the lack of multimedia
      equipment, good LAN, high-speed connection to Internet and well organized web
      design, and issues related to maintenance of equipment; and students should have
      free access to computer rooms to enable them to extend their knowledge in spare
      time; general information about health system should be available to students to
      allow them to require the role and importance of medical informatics in "real
      life". Naturally, we raise the question of unique and systematic medical
      informatics education in the whole country, irrespective of entities, nationality
      or religion of students. CONCLUSION: Medical informatics education at Medical
      School, University of Sarajevo, is based on the same concept as on prestigious
      universities all over the world and in accordance with recommendations of the
      working groups on education of EFMI and IMIA. Other medical schools in Bosnia and
      Herzegovina should employ the same methodology and system of work in order to
      have standardized education in medical informatics and to achieve high quality in
      education. To enable us to follow the European and global achievements in this
      area, the power of fact should predominate in the education system as well as in
      the health system.

PMID- 17217104
TI  - [Gastrointestinal stromal tumors (GIST)--a paradigm of successful targeted
      therapy of solid tumors].
AB  - Gastrointestinal stromal tumors (GIST) have attracted basic scientists as well as
      clinicians in the last 10 years. The reason for this is explanation of the
      pathogenetic mechanism of tumor growth by activation of c-Kit protein, followed
      by a rationally designed suppressor, a drug named imatinib. It is the first
      successful therapy for solid tumors to date, although there are other ongoing
      studies of agents with targeted action on different molecules in different
      tumors. In 80% of patients there is a clinical benefit from imatinib trreatment.
      GIST shows great diversity in clinical presentation and some questions still
      remain, such as malignant potential and prognostic criteria in these tumors.
      Imatinib therapy demonstrates many favorable effects such as acceptable toxicity
      and relative mild side effects, excellent quality of life, good patient
      compliance, etc. There are ongoing trials of new agents designated for target
      molecules, which would hopefully show benefit after developing resistance to
      imatinib.

PMID- 17217105
TI  - [Analysis of DNA samples by Abbott Commercial Tests for cystic fibrosis].
AB  - The use of commercial tests (Abbott) for cystic fibrosis, version 2 (CFv. 2) and
      3 (CFv. 3) and analysis of reaction products by capillary electrophoresis and
      genotyping on an ABI PRISM 310 genetic analyzer (Applied Biosystems) are
      presented, along with the results of test validation by concurrent processing of
      DNA samples on a Light Cycler (Roche Diagnostics) and INNO-LIPA CFTR 19
      multiparameter screening test (Innogenetics). The new Abbott commercial test for
      cystic fibrosis, CFv. 3, allows for determination of the exact number of the
      potential gene mutations (33 mutations). Other mutations may be present but
      cannot be established by using this test. Distribution frequency of CFTR gene
      mutations varies in populations, and this test covers the most frequent mutatiocs
      in the world. Based on the results obtained by validation, the use of this test
      is recommended for the following reasons: - the diagnosis of cystic fibrosis is
      reliable and relatively inexpensive since the reaction products allow for the
      most current analysis by means of capillary electrophoresis, and computer data
      processing which will soon enable routine sequencing and thereby determination of
      point mutations, - it is possible to use very small quantities of isolated DNA
      and to directly apply microvolumes of blood with EDTA, and - identification of a
      large number of current mutations has been made possible.

PMID- 17217106
TI  - [Rash and purulent lymphadenitis in cat scratch disease].
AB  - We present a case of a cat-scratch disease (CSD) presenting with typical (primary
      lesion and regional lymphadenitis) and rare (purulent lymphadenitis and
      maculopapular rash) symptoms and positive epidemiological data. Laboratory blood
      test showed normal values for routine parameters, except for mild leukocytosis (L
      12.4 x 10(9)), elevated erythrocyte sedimentation rate (SE 65/h) and moderately
      elevated asparta e-aminotransferase and alanine-aminotransferase values (AST/ALT
      48/90), fibrinogen (5.3 g/L) and C-reactive protein (CRP 85 mg/L). Cytological
      analysis of lymph node content revealed granulomatous inflammation in the first
      sample, and purulent inflammation in the second sample. In paired serum samples,
      collected on the 15th and 29th day from the onset of disease, antibodies IgG
      (titre 4096/8192) and IgM (titre 80/40) to Bartonella henselae were detected by
      using an indirect immunofluorescence assay (IFA). Antibiotic therapy with
      azithromycin (1 x 500 mg per os/5 days) was administered. Purulent lymphadenitis
      and rash, although a rare clinical manifestation in CSD, are significant clinical
      findings in differentiating CSD from other febrile illnesses accompanied with
      rash and lymphadenitis.

PMID- 17217107
TI  - [Physiological and clinical outcome of open and closed hemorrhoidectomy compared
      with stapling method according to long].
AB  - AIM OF STUDY: The aim of the study was to evaluate and inaugurate a new method
      for the treatment of hemorrhoidal disease with the usage of a stapling device
      (Long's method). PATIENTS: The study spanning two years (September 1999 to June
      2001), included 97 hospitalized patients aged 19-75 years, 42 (43.3%) female and
      55 (56.7%) male, exhibiting symptoms and signs of stage III hemorrhoidal disease.
      The patients were divided into three groups: (a) 35 patients treated with open
      hemorrhoidectomy for stage II hemorrhoidal disease; (b) 30 patients treated with
      closed hemorrhoidectomy for stage III hemorrhoidal disease; and (c) 32 patients
      treated for stage III hemorrhoidal disease by a stapling device, i. e. Long's
      method. RESULTS: Study results showed no statistically significant differences
      between either open or closed hemorrhoidectomy and Long's method in the following
      parameters: urinary retention, early bleedings during the first 48 hours, late
      bleedings, incontinence, anal stenosis, and relapses. Statistically significant
      differences between the groups of patients treated with either open or closed
      hemorrhoidectomy and those treated with Long's method were recorded in the
      following parameters: healing time, subjective feeling of pain, pain pro rata to
      quantity, and use of analgesics. CONCLUSION: Hemorrhoidectomy by Long's method is
      an ideal surgical procedure because it allows to realize to goals set on
      implementing new therapeutic methods: to achieve healing without relapse, to
      reduce postoperative pain, anal stenosis and incontinence after hemorrhoidectomy,
      to preserve the physiology of the anal canal, and to familiarize less skilled
      proctology surgeons with the simplicity of the method.

PMID- 17217108
TI  - [Iatrogenic injury of the brachiocephalic arterial trunk and its branches--case
      report].
AB  - Iatrogenic vascular traumas are increasing and their proportion exceeds 40% of
      all vascular injuries. We report on a rare case of iatrogenic injury of the
      brachiocephalic arterial trunk during surgical intervention due to
      postirradiation arteriopathy, which was successfully treated with a silver
      prosthesis graft. A 58-year-old male underwent surgery for metastases of
      papillary carcinoma of the thyroid gland, located in lymph nodes adjacent to the
      right common carotid artery and right subclavian artery. During the surgery,
      there was an intraoperative injury of the brachiocephalic arterial trunk that
      included spontaneous rupture and tear of the subclavian and common carotid
      artery, as the result of extreme fragility of the arterial wall, probably due to
      the previous irradiation therapy. Emergency sternotomy and clavicle resection
      were followed by blood flow reconstruction by use of an Y prosthesis that was
      applied for terminoterminal anastomosis between the brachiocephalic trunk to
      common carotid artery and subclavian artery. The authors concluded that
      irradiation therapy may lead to progressive arteriopathy in affected arteries.

PMID- 17217109
TI  - [A fatal case of Listeria monocytogenes sepsis and meningitis in a patient with
      Wegener's granulomatosis].
AB  - The bacillus Listeria monocytogenes is widely distributed in the environment.
      Listeria monocytogenes most often causes infection in the neonates, pregnant
      women, elderly and immunosuppressed persons. We report on a case of fatal sepsis
      and meningitis in a 59-year-old woman receiving cyclophosphamide and
      glucocorticoid therapy for Wegener's granulomatosis over a 10-year period.
      Listeriosis should be suspected in case of sepsis and/or meningitis in patients
      who receive immunosuppressive agents. Since meningitis due to Listeria
      monocytogenes is not distinguishable clinically from other types of bacterial
      meningitis, antibiotics against Listeria monocytogenes should be included in the
      initial empirical therapy of bacterial meningitis in immunosuppressed patients,
      antibiotics against Listeria monocytogenes should be included.

PMID- 17217110
TI  - [Lymphoid form of intestinal tuberculosis with miliary dissemination: case
      report].
AB  - Tuberculosis with the incidence 28-29/100000 residents still presents a major
      public health problem in Croatia. Miliary tuberculosis is uncommon cause of fever
      of unknown origin. Intestinal tuberculosis pose as diagnostic problem that can be
      identified by colonoscopy and/or explorative laparatomy involving histopathology
      and microbiology. A case is reported of a 40-year-old HIV negative patient
      admitted to the Department of Infectious Diseases after two weeks of fever,
      diarrhea, abdominal pain and weight loss. Biochemistry testing showed mild
      elevation of the erythrocyte sedimentation rate and increased serum
      aminotransferases. On admission, chest x-ray was normal and tuberculin skin test
      was negative. Crohn's disease was suspected. Computed tomography of the abdomen
      revealed solid infiltrative mass located retroperitoneally, along with enlarged
      lymph nodes. Explorative laparoscopy was necessary to confirm the diagnosis.
      Intraoperative specimens were referred for histopathologic and microbiologic
      examination, which proved the existence of granulomatous inflammation of the
      areas with caseous necrosis. Direct microscopy of the periappendicular abscess
      and Ziehl-Neelsen staining of a lymph node specimen confirmed the presence of an
      acidoresistant bacillus. The specimen culture on solid egg based agar (Lowenstein
      Jensen) and liquid broth (MGIT) showed the growth of Mycobacterium tuberculosis.
      Then the causative agent was cultured from all specimens: sputum, stool and
      urine. Repeat cheast x-ray, performed on day 30 of hospitalization, showed
      miliary dissemination to the lungs. The patient was treated with four
      antituberculotics (streptomycin, isoniazide, rifampin, ethambutol) and
      methylprednisolone for one month, then with isoniazide, rifampin and for 11
      months ethambutol. Therapy led to a decrease of abdominal lymph nodes and absence
      of miliary lesions on chest radiography after two months of treatment. Intestinal
      tuberculosis has been almost forgotten in Croatia. The latest published cases
      referred to HIV infected patients. In less than 50% of patients with intestinal
      tuberculosis the lungs are also affected, which poses a diagnostic problem.
      Crohn's disease is the most common diagnostic problem. Histopathology of a
      specimen obtained on colonoscopy and/or explorative laparoscopy can often solve
      the dilemma, as also confirmed in our patient. Of diagnostic studies, computed
      tomography has the advantage of evaluating intestinal wall involvement, which is
      important for the early diagnosis of intestinal tuberculosis. Enteroclysis and
      irrigography provide diagnostic information in the advanced stage of intestinal
      tuberculosis. In a patient with fever, abdominal disorders and parameters which
      implicate granulomatosis hepatitis or Crohn's disease, the existence of abdominal
      tuberculosis is also possible. Computed tomography and biopsy obtained on
      colonoscopy for microbiology can help in making the diagnosis and initiating
      appropriate treatment.

PMID- 17217111
TI  - [Sepsis caused by Fusobacterium necrophorum (Lemierre syndrome): a rare
      complication of acute pharyngotonsilitis].
AB  - Lemierre syndrome is defined as an acute pharyngotonsillar infection that has
      spread into the lateral pharyngeal space causing thrombophlebitis of the internal
      jugular vein with consecutive metastatic emboli. The syndrome is most often
      caused by Fusobacterium (F.) necrophorum and usually involves young, previously
      healthy people. We present a healthy 20-year-old man who suddenly developed with
      high fever and sore throat followed by dyspnea, tachypnea and cough on the third
      day of illness. His condition worsened despite outpatient intramuscular
      penicillin therapy (1600 000 IU/day). He was admitted to Dr. Fran Mihaljevic
      University Hospital for Infectious Diseases, Zagreb, on the sixth day of his
      illness with clinical signs of sepsis. Chest radiograph showed bilateral multiple
      infiltrates. F. necrophorum was isolated from blood culture. Swelling of the neck
      was also observed on the fourteenth day of illness, however, thrombophlebitis of
      the jugular vein was not diagnosed on ultrasound examination. The patient was
      treated with clindamycin for five weeks and recovered completely.

PMID- 17217112
TI  - Female genital mutilation and reproductive health in Africa.

PMID- 17217113
TI  - Genital mutilation as an expression of power structures: ending FGM through
      education, empowerment of women and removal of taboos.

PMID- 17217114
TI  - German technical cooperation (GTZ) supra-regional project: promotion of
      initiatives to end female genital mutilation (FGM).

PMID- 17217115
TI  - Being victims or beneficiaries? Perspectives on female genital cutting and
      reinfibulation in Sudan.
AB  - Female Genital Mutilation (FGM) or the more value neutral term, Female Genital
      Cutting (FGC) is widely practised in northern Sudan, where around 90% of women
      undergo the most extensive form of FGC, infibulation. One new approach to
      combating FGC in Sudan is to acknowledge the previously hidden form of FGC,
      reinfibulation (RI) after delivery, when the woman is sewn back so much as to
      mimic virginity. Based on a qualitative study in Khartoum State, this article
      explores Sudanese women's and men's perceptions and experiences of FGC with
      emphasis on RI after delivery. The results showed that both genders blame each
      other for the continuation of the practices, and the comprehensive understanding
      of the perceptions and experiences was that both the women and the men in this
      study were victims of th e consequences of FGC and RI. The female narratives
      could be understood in the three categories: viewing oneself as being "normal" in
      having undergone FGC and RI; being caught between different perspectives; and
      having limited influence on the practices of FGC and RI. The male narratives
      could be understood in the three categories: suffering from the consequences of
      FGC and RI, trying to counterbalance the negative sexual effects of FGC and
      striving in vain to change female traditions. The results indicate that the
      complexity of the persistence of FGC and RI goes far beyond being explained by
      subconscious patriarchal and maternalistic actions, related to socially
      constructed concepts of normality, female identity,tradition and religion
      a"silent" culture betweenmen and women.

PMID- 17217116
TI  - Males' preference for circumcised women in northern Ghana.
AB  - Female genital mutilation (FGM) still remains one of the challenges facing women
      in many countries around the world. Efforts to eradicate the practice are on
      going but the results are still modest due to, among other things, ingrained
      cultural traditions that expose women to serious health consequences. In Africa
      where FGM is practiced in more than 28 countries, males have been found to
      perpetuate the practice. Using baseline data on FGM collected in 1998 by the
      Navrongo Health Research Centre in Ghana, we examined factors that influence
      males' choice of marrying circumcised women. Results from regression analysis
      show that the illiterate and those who have been to primary school are more
      likely to prefer circumcised women than those with secondary and higher
      education. In addition, ethnicity and religion are also significant factors that
      influence males' preference to marry circumcised women. A number of policy
      implications are discussed.

PMID- 17217117
TI  - Trends in female circumcision between 1933 and 2003 in Osun and Ogun States,
      Nigeria (a cohort analysis).
AB  - The international movement against female circumcision gained momentum in the
      past two decades. Although recent studies report decline in the practice none has
      studied the cohort effect or provided plausible explanation for such decline.
      Changes in female circumcision occurring in two southwestern States of Nigeria
      between 1933 and 2003 were tracked in a cross-sectional survey using cohort
      analysis. 1174 female live births to 413 women were included in the analysis.
      About fifty-three percent of all females were circumcised. The prevalence dropped
      from 64.9% during the period 1933-60 to 25.7% for the period 2000-2003. For first
      order births, the corresponding rates were 58.8% and 25.0%. The decline for first
      born females comes a decade before other birth orders. Age and education of
      mother are two main factors of the decline. Global consensus or legal enforcement
      plays secondary roles. Understanding how modernisation affects the decline in
      female circumcision should receive greater attention.

PMID- 17217118
TI  - Are there "stages of change" in the practice of female genital cutting?:
      Qualitative research findings from Senegal and The Gambia.
AB  - In recent years there has been growing interest in developing theoretical models
      for understanding behaviour change with respect to the practice of female genital
      cutting (FGC). Drawing on extensive qualitative data collected in Senegal and The
      Gambia, the research reported here explores whether and how theoretical models of
      stages of behaviour change can be applied to FGC. Our findings suggest that
      individual readiness to change the practice of FGC is most dearly seen as
      operating along a continuum, and that broad stages of change characterise regions
      or segments of this continuum. Stages identified by previous researchers for
      other "problems behaviours" such as smoking inadequately describe readiness to
      change FGC since this decision is often a collective rather than individual one.
      The data reveal that the concept of stage of change is a complex construct that
      simultaneously captures behaviour, motivation, and features of the environment in
      which the decision is being made. Consequently stages identified in this research
      reflect the multidimensional nature of readiness to change the practice of FGC.
      Limitations of stage of change models as applied to FGC include the fact that
      they do not capture important aspects of the dynamics of negotiation between
      decision-makers, and do not reflect the shifting nature of opinions of
      individuals or the constellation of decision-makers. Nonetheless, we suggest the
      application of stage of change theory may provide a useful means of describing
      readiness for change of individual decisions-makers and at an aggregate level,
      patterns of readiness for change in a community. How this construct can be
      employed in quantitative population research requires further investigation.

PMID- 17217119
TI  - Analysis of perinatal mortality at a teaching hospital in Dar es Salaam,
      Tanzania, 1999-2003.
AB  - We conducted a retrospective analysis of perinatal mortality at Muhimbili
      National Hospital (MNH), Dar es Salaam, Tanzania 1999-2003 in order to
      categorise/classify perinatal deaths as well as to identify key factors in
      perinatal care that could be improved. Data were retrieved from the MNH obstetric
      database and causes of early neonatal deaths were traced from the neonatal ward
      register. The study includes all foetuses weighing =500g. A modified Nordic
      Baltic classification was used for classification of perinatal deaths. Over a 5
      year period there were 77,815 babies born with a perinatal mortality rate of 124
      per 1000 births, 78% of which was labour related stillbirth. The PMR was 913/1000
      for singleton births and 723/1000 for multiple births for babies weighing less
      than 1500 grams and 65/1000 for singleton births and 116/1000 for multiple births
      for babies weighing 2500 grams or more. Babies weighing less than 1500 grams
      contributed 26% of PMR, whereas 41% occurred in babies weighing 2500 grams or
      more. The majority (79%) of neonatal deaths had Apgar score <7 at 5 minutes and
      the most common causes of neonatal mortality were birth asphyxia (37%) and
      prematurity (29%). Labour related deaths were more common in multiple
      pregnancies. The majority of the perinatal deaths should be essentially avoidable
      through improved quality of intrapartum care. Establishment of perinatal audit at
      MNH can help identify key actions for improved care.

PMID- 17217120
TI  - Gender and oral manifestations of HIV infection among adult Nigerians.
AB  - Oral manifestations were studied in 305 adult Nigerians with HIV infection. Data
      collected were demographic (age, sex, marital status, educational status and
      occupation) and clinical (mode of transmission, general manifestations and oral
      manifestations of HIV infection). The chi- square test was used in test for
      significance between variables and p values less than 0.05 were regarded as
      significant. A total of 47.5% patients had oral manifestations. There were 67.6%
      females and 32.4% males (p <0.001). The patients ranged in age from 19-70 years.
      Heterosexual contact with multiple sex partners was the most common mode of
      transmission of infection (42.9% in females and 74.5% in males, p < 0.05).
      Candidiasis was the most common oral manifestation (78.6% in females and 78.7% in
      males p >0.05). The study concluded that similar demographic and clinical
      characteristics were observed in the occurrence of oral manifestations of HIV
      infection in both male and female Nigerians.

PMID- 17217121
TI  - Community-based study of contraceptive behaviour in Nigeria.
AB  - A cross sectional, community-based, descriptive study among women of reproductive
      age group (15-49 years) in Nigeria to explore the possible reasons for
      contraceptive non-use despite reported high awareness was carried out. Data were
      obtained using a standard questionnaire instrument and applied on 2001
      respondents. Contraceptive prevalence among sexually active respondents was 14.8%
      for all methods, 10.1% for modern methods and only 0.8% for emergency
      contraceptives. The most frequently stated reasons for non-use of contraceptives,
      among those who had never used any contraceptives but who did not want more
      children were: "did not think about it", "against religious belief" and "fear of
      side effects." Prior counseling significantly improved the continuation rate of
      contraception. Multivariate analysis showed that older, married and more educated
      women tended to use contraceptives more. Health-care providers should be trained
      to offer counseling services to all clients in general, and young, unmarried and
      uneducated women in particular in order to improve their acceptance of
      contraceptives.

PMID- 17217122
TI  - Direct questioning of genital symptoms: increasing opportunities for identifying
      and treating sexually transmitted infections in primary health-care settings.
AB  - We investigated the validity of self-reporting of genital symptoms amongst rural
      women attending primary health care clinics in rural KwaZulu-Natal. Random
      samples of 226 women were interviewed to measure self-reporting (unprompted),
      prompted and pelvic examination findings of genital symptoms. Against the
      presence of any STI self-reporting (unprompted) of symptoms had a sensitivity of
      46.1%, specificity of 64.7%, positive predictive value (PPV) of 80.0% and
      negative predictive value (NPV) of 28.0% compared to prompted symptoms which had
      a sensitivity of 78.5%, specificity of 52.9%, PPV of 80.4% and NPV of 50.0%. The
      agreement between self-reporting (unprompted) and prompted symptoms was 0.54
      (Kappa statistic). Our results suggest that in rural areas, by prompting women
      with a simple set of questions, the identification and treatment of STIs in this
      population would be enhanced, leading to better reproductive health outcomes
      including reduction of risk of infection with HIV.

PMID- 17217123
TI  - Obstructive sleep apnoea in Asia.
AB  - Obstructive sleep apnoea (OSA) syndrome is the commonest sleep-related breathing
      disorder worldwide. In Asia, the prevalence of symptomatic OSA in middle-aged men
      and women is 4.1-7.5% and 2.1-3.2%, respectively. These prevalence rates are
      similar to those reported in Caucasian populations. Obesity, an established major
      risk factor for OSA, is less common among Asians, and the reported values of body
      mass indices (BMIs) of Asians with OSA are lower than in their Caucasian
      counterparts. However, these population-based studies have consistently
      demonstrated that obesity is still the major risk factor for OSA in Asians, while
      other studies have suggested that craniofacial structural factors may make a
      greater contribution towards development of OSA in Asians than in Caucasians.
      Sleep medicine is in a developmental stage in many Asian countries, and the
      condition is likely under-recognised. Although sleep laboratories have been set
      up in various countries in Asia, the availability of this service is very
      limited. Continuous positive airway pressure is available in most parts of Asia,
      but financial constraints may limit its utility. Oral appliances have been
      postulated to have a greater role in the management of OSA in Asian patients, as
      they are likely to have more modifiable factors in their craniofacial structures,
      but this is yet to be proven. There is a great need for research and health care
      development on sleep disordered breathing in Asia, and the solution will only
      come with efforts towards promotion of awareness of this condition in both
      professional and lay communities.

PMID- 17217124
TI  - Chapter 4: childhood contact screening and management.
AB  - Young children living in close contact with a case of smear-positive pulmonary TB
      (PTB) are at particular risk of Mycobacterium tuberculosis infection and TB
      disease. Screening of the household contacts of an infectious source case is
      therefore recommended to identify children with TB and enable their prompt
      treatment, and to provide children who do not have TB with isoniazid preventive
      treatment. Isoniazid preventive treatment (IPT) is particularly beneficial in the
      case of children who are infected with the human immunodeficiency virus (HIV). A
      breastfeeding infant has a particularly high risk of infection from a mother with
      smear-positive pulmonary TB, and a high risk of developing TB. The infant should
      receive 6 months of IPT, followed by BCG vaccination. Breastfeeding can be safely
      continued in children during this period. The organisation of a system for
      comprehensive child contact screening depends on collaboration between the
      National TB Programme (NTP) and all child health providers. Close contacts of
      multidrug-resistant (MDR) TB patients should receive careful clinical followup
      for at least 2 years. If active disease develops, prompt initiation of treatment
      with a regimen designed to treat MDR-TB is recommended. On the basis of the
      currently available evidence, the World Health Organization does not recommend
      second-line drugs for chemoprophylaxis in MDR-TB contacts.

PMID- 17217125
TI  - Interferon-gamma release assays and TB screening in high-income countries: a cost
      effectiveness analysis.
AB  - OBJECTIVE: Interferon-gamma release assays (IGRA) are now available alternatives
      to tuberculin skin testing (TST) for detection of latent tuberculosis infection
      (LTBI). We compared the cost-effectiveness of TST and IGRA in different
      populations and clinical situations, and with variation of a number of
      parameters. METHODS: Markov modelling was used to compare expected TB cases and
      costs over 20 years following screening for TB with different strategies among
      hypothetical cohorts of foreign-born entrants to Canada, or contacts of TB cases.
      The less expensive commercial IGRA, Quanti-FERON-TB Gold (QFT), was examined.
      Model inputs were derived from published literature. RESULTS: For entering
      immigrants, screening with chest radiograph (CXR) would be the most and QFT the
      least cost-effective. Sequential screening with TST then QFT was more cost
      effective than QFT alone in all scenarios, and more cost-effective than TST alone
      in selected subgroups. Among close and casual contacts, screening with TST or QFT
      would be cost saving; savings with TST would be greater than with QFT, except in
      contacts who were bacille Calmette-Guerin (BCG) vaccinated after infancy.
      CONCLUSIONS: Screening for LTBI, with TST or QFT, is cost-effective only if the
      risk of disease is high. The most cost-effective use of QFT is to test TST
      positive persons.

PMID- 17217126
TI  - The cost-effectiveness of DOTS in urban Brazil.
AB  - SETTING: Rio de Janeiro, Brazil, is a middle-income setting with an estimated 1%
      adult human immunodeficiency virus (HIV) seroprevalence. OBJECTIVE: To examine
      the cost-effectiveness of DOTS in Rio de Janeiro. DESIGN: Cost-effectiveness
      analysis based on cost data and an epidemiological model based on programmatic
      outcomes from the Health Department in Rio de Janeiro, cost data from the retail
      market sector and epidemiological data from published studies. RESULTS: The 10
      year cost of a tuberculosis program treating a population of 262 000 based on
      self-administered therapy (SAT) was estimated to be $580 271 compared to $1047
      886 for DOTS. The largest portion of the DOTS budget was for staff costs and
      costs incurred by patients, both at 28%. For SAT, the largest percentage of the
      budget was allocated to medication costs, at 34%. Upgrading from SAT to DOTS
      averted 1558 cases of tuberculosis (TB, uncertainty range [UR] 1418-1704) and 143
      TB deaths (UR 131-155). The incremental cost effectiveness ratio (ICER) for DOTS
      was $300 per case averted (UR $289-$312) and $3270 per death averted (UR $3123
      $3435). In terms of disability adjusted life years (DALYs), DOTS saved 5426 DALYs
      (UR 4908-5961). The ICER for DOTS was $86 per DALY saved (UR $74-$100).
      CONCLUSIONS: DOTS is a highly cost-effective intervention in Brazil.

PMID- 17217127
TI  - Hospital DOTS linkage in Indonesia: a model for DOTS expansion into government
      and private hospitals.
AB  - BACKGROUND: To accelerate DOTS expansion, the hospital sector and specialized
      chest clinics must be engaged. OBJECTIVE: To develop a model for public-private
      partnership through DOTS expansion into public and private hospitals in
      Indonesia. DESIGN: Model development included gaining commitment from
      stakeholders, stepwise training of hospital staff, and developing unified
      networks for case management, patient referral, laboratory quality assurance,
      supervision and evaluation. RESULTS: The number of notified tuberculosis (TB)
      cases (all forms and new smear-positive) increased dramatically from baseline.
      Together, hospitals and chest clinics accounted for a significant proportion of
      the total cases notified by the province (51% of total TB cases and 56% of new
      smear-positive cases in 2004). Compared to health centers and chest clinics,
      hospitals reported lower cure and success rates. Despite the option for referral
      to health centers, the majority of patients diagnosed in hospitals and chest
      clinics in 2002-2004 opted to be fully managed by the diagnosing facility.
      CONCLUSION: The roles and strengths of hospitals differ with regard to health
      centers, providing a rational basis for linkage of these health service
      components. In Yogyakarta, linkage became effective only after establishing a
      stakeholder-based provincial coordinating (DOTS) committee as the recognized
      interface between the National Tuberculosis Programme and various providers.

PMID- 17217128
TI  - Investing time in microscopy: an opportunity to optimise smear-based case
      detection of tuberculosis.
AB  - SETTING: St. Elizabeth Hospital, rural North-west Cameroon, an area with high
      tuberculosis (TB) and human immunodeficiency virus (HIV) incidence. OBJECTIVE: To
      measure the time spent during routine sputum smear microscopy and assess whether
      reexamining slides for 10 min translates into higher case detection of smear
      positive cases. DESIGN: A prospective observational study over a 6-month period
      with three components: 1) timing of routine sputum smear examination; 2) blinded
      reexamination of all slides for 10 min and results compared with initial
      readings; and 3) blinded re-examination, by the original microscopists, of a
      portion of false-negative slides mixed with true negatives for 10 min. RESULTS: A
      total of 204 patients submitted 612 sputum specimens for screening. The median
      routine examination time was 2 min 6 seconds (interquartile range 1:30-2:30). A
      10 min examination significantly increased the number of positive smears from 82
      to 116 (P = 0.0083), and overall case detection from 28 to 48 patients (P =
      0.011). On review by the original readers, more than half of the false-negative
      slides were reported as positive after 10 min. CONCLUSION: Sputum smear
      microscopy has low sensitivity if performed too quickly, and 10 min re
      examination significantly increases case detection. Ensuring that smears are
      examined for the recommended duration may be a simple and low-cost way to improve
      case detection.

PMID- 17217129
TI  - Risk factors associated with default among new pulmonary TB patients and social
      support in six Russian regions.
AB  - SETTING: Tuberculosis (TB) services in six Russian regions in which social
      support programmes for TB patients were implemented. OBJECTIVE: To identify risk
      factors for default and to evaluate possible impact of social support. METHODS:
      Retrospective study of new pulmonary smear-positive and smear-negative TB
      patients registered during the second and third quarters of the 2003. Data were
      analysed in a case-control study including default patients as cases and
      successfully treated patients as controls, using multivariate logistic regression
      modelling. RESULTS: A total of 1805 cases of pulmonary TB were enrolled. Default
      rates in the regions were 2.3-6.3%. On multivariate analysis, risk factors
      independently associated with default outcome included: unemployment (OR 4.44;
      95%CI 2.23-8.86), alcohol abuse (OR 1.99; 95%CI 1.04-3.81), and homelessness (OR
      3.49; 95%CI 1.25-9.77). Social support reduced the default outcome (OR 0.13;
      95%CI 0.06-0.28), controlling for age, sex, region, residence and acid-fast
      bacilli (AFB) smear of sputum. CONCLUSION: Unemployment, alcohol abuse and
      homelessness were associated with increased default outcome among new TB
      patients, while social support for TB patients reduced default. Further
      prospective randomised studies are necessary to evaluate the impact and to
      determine the most cost-effective social support for improving treatment outcomes
      of TB in patients in Russia, especially among populations at risk of default.

PMID- 17217130
TI  - High success rate of TB treatment among Bhutanese refugees in Nepal.
AB  - SETTING: Camps for refugees from Bhutan in south-east Nepal. OBJECTIVES: To
      evaluate the outcome of treatment of tuberculosis (TB) cases in the refugee
      camps. DESIGN: Cohort analysis of results of treatment of cases started on
      treatment from mid-July 1999 to mid-July 2004. RESULT: A total of 1214 patients
      with TB were notified in the programme. Among these, 631 (52%) were new smear
      positive pulmonary tuberculosis (PTB) cases, 175 (14%) new smear-negative PTB
      cases, 290 (24%) new extra-pulmonary TB (EPTB) cases and 118 (10%) smear-positive
      retreatment cases. Treatment success was achieved in 1061 (94%). The proportion
      of new non-smear-positive cases who died on treatment was significantly higher
      than the corresponding figure for new smear-positive cases (RR 7.57, 95%CI 3.74
      15.32 for new smear-negative and 4.22, 95%CI 2.08-8.55 for EPTB). CONCLUSION:
      High cure rates and low bacteriological failure rates can be achieved in refugee
      settings if there is close coordination and collaboration between the local
      health agencies and the National Tuberculosis Programme of the host country.

PMID- 17217131
TI  - Factors influencing the successful treatment of infectious pulmonary
      tuberculosis.
AB  - SETTING: Achieving successful treatment of infectious pulmonary tuberculosis
      (PTB) could reduce the spread of tuberculosis (TB) and the emergence of multidrug
      resistance. OBJECTIVE: To explore factors associated with successful treatment
      for sputum-positive PTB. DESIGN: This study used a population-based retrospective
      cohort design. All PTB patients residing in southern Taiwan recorded in the
      tuberculosis registry from 1 January to 30 June 2003 were identified. Each
      patient's medical record was requested from treating hospitals and
      retrospectively reviewed for 15 months after the date PTB was confirmed. RESULTS:
      There were 399 PTB patients included in the study. Factors significantly
      associated with successful treatment included treatment by pulmonologists (OR
      1.93), receiving directly observed therapy (DOT) (OR 1.76) and receiving
      treatment at the chest hospital (OR 5.41). Patients of advanced age were less
      likely to achieve treatment success (OR 0.97). Among patients treated by
      pulmonologists, those treated at the chest hospital had a significantly higher
      treatment success rate than those treated at other institutions (94.1% vs.
      69.9%). CONCLUSIONS: Patients treated with DOT and by pulmonologists, especially
      at the chest hospital, had a higher treatment success rate. DOT and training of
      care professionals and institutions are therefore important factors that affect
      the successful treatment of TB.

PMID- 17217132
TI  - Developing a socio-economic measure to monitor access to tuberculosis services in
      urban Lilongwe, Malawi.
AB  - OBJECTIVES: To develop locally appropriate measures of poverty for the National
      Tuberculosis Programme (NTP), Malawi, and to assess access to tuberculosis (TB)
      services by different socio-economic groups by establishing a socio-economic
      profile of current TB patients DESIGN: A quantitative proxy measure of poverty
      was developed through regression analysis of data from the 1998 national Malawi
      Integrated Household Survey. A qualitative assessment of poverty was conducted in
      poor and non-poor settlements in urban Lilongwe to identify key indicators of
      socio-economic status. Both quantitative and qualitative indicators were used to
      assess the socioeconomic status of 179 TB patients who participated in a cross
      sectional survey. FINDINGS: The proxy measure of poverty and the qualitative
      indicators demonstrated similar ability to measure the poverty status of
      patients. The poverty head count among patients using the quantitative and
      qualitative indicators were 78% and 70%, respectively. Geographical analysis
      showed that 60% were from non-poor areas and only 15% (26/139) were from squatter
      settlements. CONCLUSION: This study established a strategy for monitoring access
      to TB services using a proxy measure of poverty and qualitative indicators. This
      is a vital first step in developing an evidence base for pro-poor equitable TB
      services.

PMID- 17217133
TI  - Alliance and compliance in tuberculosis treatment of older Pakeha people in
      Auckland, New Zealand.
AB  - SETTING: A community-based ethnography of tuberculosis (TB) treatment of
      'European' New Zealanders in Auckland was completed in 2003. OBJECTIVE: To
      document and analyse the nature of the process of care in this population where
      the majority of patients are older with other health and social complications.
      DESIGN: Data collection included repeated semi-structured interviews with all
      patients who were willing and able to give consent, semi-structured interviews on
      health and TB with matched participants without TB, discussions with health care
      providers, participant observation with TB patients, readings of patient records
      and monitoring of TB in the media. Reiterative inductive analyses were made of
      transcripts, field notes and textual materials. RESULTS: Eight patients from 2003
      (out of a possible nine) and one patient from 1997 participated. All were aged 47
      75 years. They represent a wide socio-economic range. All completed treatment.
      The contribution of multidimensional care, from initial acceptance through
      exigencies of treatment to successful recovery, is evident in the participants'
      narratives. The public health nurse is a key support and a lynchpin in the
      patients' support network. CONCLUSION: A model of care including alliances
      between patients and care givers as part of treatment is clearly successful in
      this population group. This study has implications for older cohorts in other low
      incidence countries.

PMID- 17217134
TI  - Incidence of and risk factors for severe liver toxicity in HIV-infected patients
      on anti-tuberculosis treatment.
AB  - OBJECTIVE: To assess the incidence and risk factors for severe liver toxicity in
      human immunodeficiency virus (HIV) infected patients on anti-tuberculosis
      treatment and the impact of patients' characteristics and concomitant medications
      instituted during the first week of antituberculosis treatment. METHODS: HIV
      infected patients referred to six French hospitals between 1 January 1992 and 31
      December 2004, with confirmed or 'presumptive' tuberculosis (TB). Liver toxicity
      was studied during the first 2 months of TB treatment. RESULTS: During the 12
      years of the study period, 144 patients were enrolled. Severe liver toxicity
      developed in 15 (10.7%). The median time to development of liver toxicity was 14
      days. In the univariate analysis, high baseline bilirubin levels (P = 0.004), CD4
      cell counts between 50 and 100 cells/mm3 (P = 0.022) and the use of fluconazole
      (P = 0.0005) were associated with liver toxicity. In the multivariate analysis,
      independent risk factors were abnormal baseline alanine aminotransferase (ALT) (P
      = 0.028) and bilirubin levels (P = 0.033) and the use of fluconazole (P = 0.008).
      CONCLUSION: Severe liver toxicity is frequent, and occurs early in the course of
      anti-tuberculosis treatment. ALT and bilirubin levels should be closely monitored
      during the first month of treatment, especially in patients with high baseline
      ALT or bilirubin levels. We suggest caution when prescribing fluconazole and anti
      tuberculosis drugs concomitantly, although this needs to be confirmed and further
      investigated.

PMID- 17217135
TI  - Indications for percutaneous endoscopic gastrostomy in complex tuberculosis
      patients.
AB  - OBJECTIVES: Percutaneous endoscopic gastrostomy (PEG) is a widely used method for
      providing long-term administration of tube feeding. Different indications in
      relation to diseases, impairments and nutritional factors for PEG placement have
      been mentioned in guidelines. Treatment with PEG has not been described
      previously for tuberculosis (TB). Our aim was to identify and describe
      indications and contributing factors for PEG placement in TB patients. METHODS: A
      retrospective medical record review was conducted of 32 TB patients who required
      PEG from March 1996 to April 2004. Indications and contributing factors for PEG
      placement were analysed. RESULTS: PEG placement was based on three different
      indications. In 18 patients, PEG was used to administer tube feeding, in 4
      patients anti-tuberculosis drugs were administered and in 10 patients both tube
      feeding and antituberculosis drugs were administered. Contributing factors for
      PEG placement were swallowing disabilities, weakness, anti-tuberculosis drugs and
      their side effects, pain of neuralgic origin, hiccups and refusal of food and
      drugs. CONCLUSIONS: In TB, imminent and overt malnutrition, as well as the
      administration of drugs with a curative aim, are new indications for PEG
      placement. The use of PEG can overcome various problems in TB treatment and
      prevent treatment default.

PMID- 17217136
TI  - Tuberculoma of the brain: a series of 16 cases treated with anti-tuberculosis
      drugs.
AB  - OBJECTIVES: To describe the clinical presentation, radiological findings and
      outcome of treatment with antituberculosis drugs in 16 cases of intracranial
      tuberculoma. DESIGN: Consecutive cases admitted with tuberculoma to the National
      Center for Neurological Diseases in Khartoum, Sudan, were included in the study.
      The diagnosis was based on clinical and neuro-imaging features and response to
      anti-tuberculosis treatment. Histopathology of material from the brain or other
      extracranial tissues was available in seven cases. RESULTS AND CONCLUSIONS: The
      commonest presenting features were headache (100%), generalized convulsions
      (68.7%) and hemiparesis (56.2%). Computerised axial tomography/magnetic resonance
      imaging (CT/MRI) showed single or multiple lesions that showed intense contrast
      enhancement and perilesional edema. The lesions completely cleared on anti
      tuberculosis treatment in the majority of survivors (13/15). Partial clearance of
      lesion was associated with late presentation, multiple large lesions and advanced
      miliary disease. We advocate early empirical trial of anti-tuberculosis drugs for
      intracranial tuberculoma even after a presumptive diagnosis, particularly in
      areas where the infection is endemic.

PMID- 17217137
TI  - Skin and soft tissue infection caused by non-tuberculous mycobacteria.
AB  - SETTING: A medical centre in Taipei, Taiwan. OBJECTIVE: To investigate the trend
      and characteristics of patients with non-tuberculous mycobacteria (NTM) related
      skin and soft tissue infection. DESIGN: A total of 63 patients with culture
      proven diseases were identified from January 1997 to December 2004. The medical
      records of all patients were reviewed. RESULTS: Twenty-seven patients were
      infected with rapidly growing mycobacteria (RGM), 19 with Mycobacterium marinum,
      six with M. avium complex (MAC), five with M. kansasii and six with other
      species. Most patients presented with a protracted cutaneous lesion without
      systemic symptoms, and two thirds of the patients had a history of exposure.
      Seventy-three per cent of the lesions involved the extremities. Underlying
      illness with suppressed immunity was documented in 30.2% of the patients, and was
      most prevalent in patients with MAC (100%) and M. kansasii (60%). Of the
      patients, 62% underwent at least one surgical intervention, and 77.8% received
      treatment with different antimicrobial combinations. Most patients (86%)
      recovered completely. Granulomatous inflammation was found in 88.9% of biopsied
      tissue associated with M. marinum infection, 31.8% with RGM and 25.0% with MAC.
      CONCLUSION: A combination of surgery and antimicrobials cured most patients with
      microbiologically proven localised NTM skin and soft tissue infection.

PMID- 17217138
TI  - Fat and fish intake and asthma in Japanese women: baseline data from the Osaka
      Maternal and Child Health Study.
AB  - OBJECTIVE: It remains controversial whether the intake of n-3 polyunsaturated
      fatty acids and fish is preventive against asthma. This cross-sectional study
      investigated the relationship between fat and fish intake and the prevalence of
      asthma using baseline data from a prospective study. DESIGN: The subjects were
      1002 pregnant Japanese females. A diet history questionnaire was used to assess
      dietary habits. Current asthma and asthma after age 18 were defined as present if
      subjects had been treated with medications at some time in the previous 12 months
      and after reaching the age of 18, respectively. RESULTS: Fish consumption was
      independently associated with a decreased prevalence of asthma after age 18 and
      current asthma. A significant inverse relationship was observed between the ratio
      of n-3 to n-6 polyunsaturated fatty acid intake and the prevalence of current
      asthma, but not asthma after age 18. Intake of total fat, saturated,
      monounsaturated, n-3 polyunsaturated and n-6 polyunsaturated fatty acids,
      cholesterol, meat, eggs or dairy products was not evidently related to either
      outcome for asthma. CONCLUSION: Our results suggest that fish consumption and the
      high ratio of n-3 to n-6 polyunsaturated fatty acid intake may be associated with
      a reduced prevalence of asthma in young female Japanese adults.

PMID- 17217139
TI  - Compliance with DOTS diagnosis and treatment recommendations by private
      practitioners in Kerala, India.
AB  - The Indian government has a national tuberculosis (TB) plan based on DOTS
      recommendations. The private health sector plays an increasing role in health
      care provision in India, and a public-private mix (PPM) project has been
      introduced to standardise TB diagnosis and treatment methods in Kerala, India.
      This study interviewed 45 private practitioners (PPs) to evaluate diagnostic,
      treatment and reporting practices, of whom 80% diagnose with sputum microscopy
      and 43% treat all of their patients according to the treatment regimens
      recommended by the DOTS strategy. This study demonstrates that the current
      management of TB by private practitioners in Kerala is still in need of
      improvement.

PMID- 17217140
TI  - No association between the +874T/A single nucleotide polymorphism in the IFN
      gamma gene and susceptibility to TB.
AB  - A single nucleotide polymorphism (SNP), +874T/A, in the first intron of the
      interferon-gamma (IFN-gamma) gene, has presented associations with human
      susceptibility to tuberculosis (TB) in some ethnic populations, but not in
      others. In this population-based case-control study with adult TB patients from
      Houston, Texas, we found no significant differences of + 874T/A genotypic
      frequencies between cases and ethnically-matched controls or between advanced
      forms of TB disease (extra-pulmonary involvement or presence of cavitary disease)
      and pulmonary TB. Given possible sample size limitations, our results suggest
      that the IFN-gamma +874T/A mutation has no association with TB susceptibility or
      TB disease severity.

PMID- 17217141
TI  - Outcomes of multidrug-resistant tuberculosis treatment in HIV-positive patients
      in New York City, 1990-1997.

PMID- 17217142
TI  - Moxifloxacin-induced arthropathy.

PMID- 17217143
TI  - Pacemaker infections due to rapidly growing mycobacteria: further experience.

PMID- 17217144
TI  - Prophylaxis and treatment of venous thromboembolism in patients with cancer.

PMID- 17217145
TI  - QT dispersion: time for a revival?

PMID- 17217146
TI  - Beyond events and molecules in internal medicine: sport and exercise as
      treatment.

PMID- 17217147
TI  - Beyond medical futility: a proposed taxonomy of ultra vires acts in medicine.
AB  - When is a physician's act non-medical, and how might such non-medical acts be
      classified? One approach, analogous to the substantive due process inquiry
      employed by American courts weighing the constitutionality of legislative acts,
      would involve consideration of the following questions: 1) Is a legitimate
      medical goal being pursued? 2) Are the means being employed legitimately medical?
      3) Are the goals and means appropriately related? Accordingly, a physician acts
      medically when employing legitimate and appropriate medical means in pursuit of a
      legitimate medical goal. In contrast, when the goals pursued or means employed
      are not legitimately medical, or when the two are not appropriately related, the
      act is medically ultra vires ("beyond the powers")--that is, an act beyond the
      physician's power or authority--and consequently non-medical. Medically ultra
      vires acts may be further sub-classified depending upon which prong of the above
      trident is defective. Where the goal of the act, though achievable, is not
      legitimately medical, the act is medically ultra vires because of goal
      illegitimacy, or medically ultra fines ("beyond the ends"). Where the means
      employed are not legitimately medical, the act is medically ultra vires because
      of means illegitimacy, or medically ultra modos ("beyond the means"). Where the
      means and goals are not appropriately related, the act is medically ultra vires
      because of means-goals disjunction, or medically ultra nexus ("beyond the
      connection"). Medical futility (where the medical goal in question, albeit
      legitimate, cannot be achieved by the act under consideration) represents the
      paradigmatic example of the latter.

PMID- 17217148
TI  - Prophylaxis and treatment of venous thromboembolism in patients with cancer: an
      update.
AB  - The close correlation between venous thromboembolism (VTE) and cancer has been
      known for some time, and numerous reports in the literature have highlighted the
      epidemiological significance. Moreover, VTE has a substantial impact on morbidity
      and mortality in oncological patients. The prevention and treatment of VTE are
      important aspects of the clinical management of patients with cancer. The
      presence of a tumour is often associated with thrombotic complications that are
      more difficult to diagnose, and sometimes make the treatment of VTE less
      effective and more likely to cause haemorrhages.

PMID- 17217149
TI  - Increased QT dispersion: a negative prognostic finding in chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a highly prevalent
      syndrome, deeply affecting the cardiovascular system as well as the lungs. We
      investigated the prognostic role of the QT interval and QT dispersion (QTD) in
      predicting all-cause, respiratory and cardiovascular mortality in COPD, and the
      relationship between these electrocardiographic parameters and pulmonary function
      in a prospective longitudinal study. METHODS: We studied 246 COPD patients
      without significant co-morbidities, with a mild to moderate functional
      impairment, admitted to the Department of Internal Medicine from January 1995 to
      December 2001, performing a 5-year mean follow-up (5-116 months) up to August
      2004. After clinical stabilisation, an electrocardiogram and functional
      respiratory tests were obtained, allowing measurement of the QT interval and QTD,
      forced vital capacity (FVC), forced expiratory volume at 1 s (FEV1), inspiratory
      capacity, FEV1/FVC ratio, partial oxygen pressure and partial carbon dioxide
      pressure in arterial blood. RESULTS: At the end of the follow-up period, 81
      patients were dead, 165 still alive; 36 died because of respiratory causes, 23
      because of cardio-cerebrovascular events, 21 because of cancer (mainly lung
      cancer). A significant high incidence of sudden cardiac death was observed. QTD
      and QTcD showed a significant relationship with respiratory functional
      parameters. Maximal QT interval, QTcD and QTD appear to be independent predictors
      of all-cause, cardiovascular and respiratory mortality (relative risk 1.94, 3.22,
      2.88, respectively). Age > 65 years, partial oxygen pressure < 60 mmHg and
      inspiratory capacity < 80% of the predicted value were the only other independent
      predictive parameters. CONCLUSIONS: Maximal QT interval, QTD and QTcD are
      independent predictors of mortality. A significant incidence of cardiac sudden
      death was observed. These findings suggest the need for a global and
      multidisciplinary risk assessment in COPD patients. Intriguing relationships
      between the QTD and functional respiratory parameters were also observed.

PMID- 17217150
TI  - Changes in serum triglycerides and high-density lipoprotein concentration and
      composition after a low-fat mixed meal. Effects of gender and insulin resistance.
AB  - OBJECTIVE: Postprandial lipemia is generally studied after a test meal that
      provides most of the calories as fat and that does not reflect the common food
      intake. We investigated postprandial changes in serum triglycerides (TG) and in
      high-density lipoprotein (HDL) concentration and composition after a regular meal
      poor in fat (30% of calories). METHODS: Fifty-four women and 54 men had breakfast
      at 8:00 a.m. (12% of daily calories) and lunch at 12:30 p.m. (53% of daily
      calories). RESULTS: With respect to fasting values, TG increased more in men (24%
      at 2:30 p.m. and 30% at 5:00 p.m.) than in women (19% and 23%, respectively). HDL
      cholesterol decreased by 4% both in men and women at 2:30 p.m., and in both
      genders levels returned towards baseline levels at 5:00 p.m. Apolipoprotein A-I
      (apo A-I) significantly decreased in men (-3% at 2:30 p.m.), but did not change
      in women. The apo A-I/HDL cholesterol ratio significantly increased by 3% in men
      at 2:30 p.m. and by 5% both in men and women at 5:00 p.m. Postprandial serum TG
      were higher and HDL cholesterol and apo A-I were lower in subjects of both
      genders with insulin resistance (high HOMA(IR)) than in those with low HOMA(IR).
      The greatest increase in serum TG (39%) was observed in men with high HOMA(IR).
      HDL cholesterol and apo A-I significantly decreased and the apo A-I/HDL-C ratio
      significantly increased only in this subgroup of subjects. CONCLUSIONS: Ingestion
      of low doses of fat in a mixed meal is followed by variable increases of serum
      TG, and the greatest response is found in insulin-resistant men. In this subset
      of subjects, postprandial hypertriglyceridaemia is associated with alterations in
      HDL that might be consistent with an increased risk of cardiovascular disease.

PMID- 17217151
TI  - Positive stress test in a patient with patent coronary artery grafts.

PMID- 17217152
TI  - Verified level 1 pediatric trauma centers.

PMID- 17217153
TI  - Building a trauma center and system in Tuscany, Italy.
AB  - BACKGROUND: Growing evidence supports the premise that adult trauma centers lower
      the risk of death for severely injured patients. The same principles have been
      applied to the pediatric population and mounting research suggests that, as in
      the adult population, gravely injured children have better outcomes at pediatric
      trauma centers where personnel trained and experienced in the specific needs and
      unique physiology of injured children provide care. As in the United States,
      acute traumatic injury represents an important public healthcare concern to the
      Tuscan regional government whose goal is to maximize clinical outcomes within
      available resources. In order to address this problem, the Tuscan regional
      government has created a new and innovative collaboration between the Meyer
      Pediatric Hospital/University of Florence School of Medicine and the Children's
      Hospital Boston/Harvard Medical School to build a pediatric trauma center and
      regional pediatric trauma referral system. GOALS AND OBJECTIVES: This long-term
      international initiative will seek to develop a demonstration model for pediatric
      trauma care that may later be replicated elsewhere. The initial goals of the
      project will focus on expanding the role of the pediatricians working in the
      emergency department to include the acute care of medical, surgical, orthopedic
      and multiple trauma patients. This new configuration will closely resemble the
      single provider model of emergency medical care commonly utilized in the United
      States. During this transition period to a more broadly trained emergency
      physician, a multi-disciplinary trauma team will be created and pediatric trauma
      clinical practice guidelines will be introduced into the emergency department and
      inpatient care units. Systems measurements will be achieved through a
      comprehensive quality improvement and risk management program. Ultimately, all
      Tuscan regional pediatric major trauma will be consolidated at the Meyer
      Pediatric Hospital in Florence.

PMID- 17217154
TI  - A 2.5-year-old child with a history of a foreign body aspiration.

PMID- 17217155
TI  - Renaissance of a res publica clinical research: global access to trial registers.

PMID- 17217156
TI  - Isolated hepatic tuberculoma after orthotopic liver transplantation: a case
      report.

PMID- 17217157
TI  - Weight loss, articular pain and bone fractures: neoplastic disease or
      malabsorption syndrome?

PMID- 17217158
TI  - A novel nonsense mutation in exon 2 of the factor IX gene resulting in severe
      haemophilia B.

PMID- 17217159
TI  - Calciphylaxis: evolving concepts.

PMID- 17217160
TI  - Effects of eicosapentaenoic acid (EPA) on adiponectin gene expression and
      secretion in primary cultured rat adipocytes.
AB  - Adiponectin, a hormone produced by adipocytes, is involved in glucose metabolism
      and insulin sensitivity. The production of this adipokine is impaired in obesity
      and insulin resistance. Eicosapentaenoic acid (EPA) is a dietary n-3
      polyunsaturated fatty acid that improves insulin sensitivity in several models of
      obesity and diabetes, which has been suggested to be related to adiponectin
      induction. An increase in adiponectin production has been also associated with an
      up-regulation of the transcriptional factor PPARgamma. The aim of this trial was
      to evaluate the direct effects of EPA on adiponectin gene expression and protein
      secretion in isolated rat adipocytes as well as to explore the potential
      mechanisms involved. A comparative study with troglitazone, a PPARgamma agonist,
      was also performed. For these purposes, primary rat adipocytes were cultured with
      EPA (100 and 200 microM) and with troglitazone (10 microM) for 96 hours. Both EPA
      and troglitazone improved glucose utilization by adipocytes. As expected,
      troglitazone enhanced adiponectin secretion and increased PPARgamma gene
      expression. However, EPA significantly decreased adiponectin gene expression and
      protein secretion and reduced PPARy mRNA levels, suggesting that the inhibition
      of adiponectin by EPA is likely to be secondary to the down-regulation of this
      adipogenic transcription factor. Moreover, these results suggest that other
      mechanisms different from the direct stimulation of adiponectin by the fatty acid
      are underlying the insulin-sensitizing properties observed after EPA treatment in
      vivo.

PMID- 17217161
TI  - Diferential gene expression and adiposity reduction induced by ascorbic acid
      supplementation in a cafeteria model of obesity.
AB  - Obesity is considered as an inflammatory disease, in which free radical-induced
      oxidative stress and excessive intake of macronutrients exacerbate their
      symptoms. In this context, we assessed in rats the possible preventive effect of
      the supplementation with an antioxidant molecule, ascorbic acid, in order to
      reduce the adiposity induced by the intake of a high-fat diet. For this purpose,
      during 56 days, three groups of male Wistar rats were fed on: a) standard
      pelleted diet, b) Cafeteria diet, c) ascorbate-supplemented (750 mg/kg of body
      weight) Cafeteria diet. At the end of the experimental period, microarray
      analysis was used to identify genes transcriptionally induced or repressed by
      both experimental dietary models (Cafeteria diet supplemented or not with
      ascorbic acid) in subcutaneous adipose tissue. Dietary ascorbic acid was able to
      protect against high fat diet effects, reducing the increase of body weight,
      total body fat and enlargement of different adipose depots induced by the
      Cafeteria diet without affecting food intake. An association analysis accurately
      and differentially allowed the detection of gene expression changes related with
      adiposity and insulin resistance. The genes that more strongly correlated with
      body fat and HOMA insulin resistance index were involved in adipocyte
      differentiation, lipid and glucocorticoid metabolism, cell cycle regulation, as
      well as in several insulin-induced processes. Some other transcripts are
      regulated by the vitamin C-mediated reduction of adiposity, such as genes that
      participate in glucocorticoid metabolism, adipogenesis, pentose phosphate
      pathway, or tricarboxylic acid cycle. This strategy was able to link variations
      in adipose tissue gene expression with markers of diet-induced obesity in rats,
      such as insulin resistance and body fat content.

PMID- 17217162
TI  - Effects of trans-10,cis-12 conjugated linoleic acid on body fat and serum lipids
      in young and adult hamsters.
AB  - The aim of the present work was to determine whether t-10, c-12 conjugated
      linoleic acid (CLA) feeding was able to reduce body fat accumulation and improve
      the serum lipid profile in adult hamsters fed an atherogenic diet, in order to
      compare these effects with those observed in young growing hamsters. Young and
      adult hamsters were fed semi-purified atherogenic diets supplemented with 0.5 %
      linoleic acid or 0.5% t-10, c-12 CLA for 6 weeks. Body weight and food intake
      were measured every two days. Adipose tissue from different anatomical locations,
      liver and gastrocnemious muscle were dissected and weighed. Cholesterol,
      triacylglycerols, non-esterified fatty acids and proteins were determined
      spectrophotometrically and water content by gravimetry. In young hamsters, no
      significant differences were found in food intake, final body weight and
      gastrocnemious muscle weight. White adipose tissue weights were reduced, liver
      weight was increased and cholesterol and triacyl-glycerols in both serum and
      liver were reduced. In adult hamsters, CLA feeding decreased food intake and
      adipose tissue weights. No changes were observed in other parameters. The present
      study demonstrates that age has an influence in hamster responsiveness to t-10, c
      12 CLA because, although when this isomer is added to an atherogenic diet it
      reduces body fat accumulation in both young and adults hamsters, the lessening of
      the effects on serum lipids brought about by atherogenic feeding is only observed
      in young animals. Moreover, it is clear that liver is a target for CLA in young
      but not in adult hamsters.

PMID- 17217163
TI  - Prolonged treatment with the beta3-adrenergic agonist CL 316243 induces adipose
      tissue remodeling in rat but not in guinea pig: 1) fat store depletion and
      desensitization of beta-adrenergic responses.
AB  - Beta3-adrenergic agonists have been considered as potent antiobesity and
      antidiabetic agents mainly on the basis of their beneficial actions discovered
      twenty years ago in obese and diabetic rodents. The aim of this work was to
      verify whether prolonged treatment with a beta3-adrenergic agonist known to
      stimulate lipid mobilisation, could promote desensitization of beta-adrenergic
      responses. Wistar rats and guinea pigs were treated during one week with CL
      316243 (CL, 1 mg/kg/d) by implanted osmotic minipumps. In control animals, beta3
      adrenergic agonists were lipolytic in rat but not in guinea pig adipocytes. CL
      treatment did not alter body weight gain in both species, but reduced fat stores
      in rats. Lipolysis stimulation by forskolin was unmodified but responses to beta1
      , beta2- and beta3-agonists were reduced in visceral or subcutaneous white
      adipose tissues of CL-treated rats. Similarly, the beta3-adrenergic-dependent
      impairment of insulin action on glucose transport and lipogenesis in rat
      adipocytes was diminished after CL-treatment. In rat adipocytes, [125I]ICYP
      binding and beta3-adrenoceptor mRNA levels were reduced after sustained CL
      administration. These findings show that CL 316243 exerts (beta3-adrenergic
      lipolytic and antilipogenic effects in rat adipocytes. These actions, which are
      likely involved in the fat depletion observed in rat, also lead to the
      desensitization of all beta-adrenergic responses. Therefore this desensitization,
      together with the lack of slimming action in guinea pig, seriously attenuates the
      usefulness of beta3-agonists as antiobesity agents, and may explain why such
      agonists have not been conducted to a widespread clinical use.

PMID- 17217164
TI  - Prolonged treatment with the beta3-adrenergic agonist CL 316243 induces adipose
      tissue remodeling in rat but not in guinea pig: 2) modulation of glucose uptake
      and monoamine oxidase activity.
AB  - Beta3-adrenergic agonists are well-recognited to promote lipid mobilisation and
      adipose tissue remodeling in rodents, leading to multilocular fat cells enriched
      in mitochondria. However, effects of beta3-adrenergic agonists on glucose
      transport are still controversial. In this work, we studied in white adipose
      tissue (WAT) the influence of sustained beta3-adrenergic stimulation on the
      glucose transport and on the mitochondrial monoamine oxidase (MAO) activity. As
      one-week administration of CL 316243 (CL, 1 mg/kg/d) induces beta-adrenergic
      desensitization in rat but not in guinea pig adipocytes, attention was paid to
      compare these models. When expressing glucose uptake as nmoles of 2
      deoxyglucose/100 mg cell lipids, maximally stimulated uptake was increased in
      adipocytes of WAT from treated rats but not from treated guinea pigs. However,
      basal hexose uptake was also increased in CL-treated rats and, as a consequence,
      the dose-dependent curves for insulin stimulation were similar in control and CL
      treated rats when expressed as fold increase over basal. Insulin-induced
      lipogenesis was unchanged in rat or guinea pig adipocytes after CL-treatment. The
      glucose carriers GLUT4 and corresponding mRNA were increased in subcutaneous WAT
      or in brown adipose tissue (BAT) but not in visceral WAT or muscles of CL-treated
      rats. There was an increase of MAO activity in WAT and BAT, but not in liver, of
      CL-treated rats while no change was detected in guinea pigs. These findings show
      that only rat adipocytes, which are beta3-adrenergic-responsive, respond to
      chronic beta3-AR agonist by an increase of GLUT4 content and MAO activity,
      despite a desensitization of all beta-adrenoceptor subtypes.

PMID- 17217165
TI  - Increased monoamine oxidase and semicarbazide-sensitive amine oxidase activities
      in white adipose tissue of obese dogs fed a high-fat diet.
AB  - Adipocytes express two types of amine oxidases: the cell surface semicarbazide
      sensitive amine oxidase (SSAO) and the mitochondrial monoamine oxidase (MAO). In
      human abdominal subcutaneous adipose tissue, it has been reported that SSAO
      substrates stimulate glucose transport and inhibit lipolysis while MAO activity
      is decreased in obese patients when compared to age-matched controls. However, no
      information has been reported on visceral WAT. To further investigate the obesity
      induced regulations of MAO and SSAO in white adipose tissue (WAT) from different
      anatomical locations, enzyme activities and mRNA abundance have been determined
      on tissue biopsies from control and high-fat fed dogs, an obesity model already
      described to be associated with arterial hypertension and hyperinsulinemia. MAO
      activity was increased in the enlarged omental WAT of diet-induced obese dogs,
      but not in their mesenteric WAT, another intra-abdominal fat depot. Subcutaneous
      WAT did not exhibit any change in MAO activity, as did the richest MAO-containing
      tissue: liver. Similarly, SSAO was increased in omental WAT of diet-induced obese
      dogs, but was not modified in other WAT and in aorta. The increase in SSAO
      activity observed in omental WAT likely results from an increased expression of
      the AOC3 gene since mRNA abundance and maximal benzylamine oxidation velocity
      were increased. Finally, plasma SSAO was decreased in obese dogs. Although the
      observed regulations differ from those found in subcutaneous WAT of obese
      patients, this canine model shows a tissue- and site-specific regulation of
      peripheral MAO and SSAO in obesity.

PMID- 17217166
TI  - Diversity of metabolic syndrome risk factors in obese children and adolescents.
AB  - The aim of this study was to investigate the frequency of metabolic syndrome (MS)
      variables in a group of spanish obese children and adolescents, to asses MS
      prevalence in this population and to describe it's relationship with other
      metabolic risk factors. 103 children were studied : 54 male and 49 female, mean
      age 10.08+/-2.3 with exogenous obesity. Obesity was defined when BMI was higher
      than the age and sex specific equivalent to 30 kg/m(2) in adults. MS variables
      considered were waist circumference, blood pressure, fasting blood triglycerides,
      fasting glucose/insulin and HDL-cholesterol. The children were considered as
      having the MS when three or more characteristics showed abnormal values according
      to Cook and De Ferranti definitions. HOMA index, ApoB and ApoA1 were studied too.
      The most frequent features of the metabolic syndrome were excess waist
      circumference and hypertension. The MS markers with the lowest frequency were
      dyslipidemia and fasting hyperglicemia. MS prevalence was 29,9% (Cook et al.
      criteria) and 50% (De Ferranti et al. criteria). Fasting insulin and HOMA index
      values increased significantly (p < 0.05) when three or more abnormalities of the
      MS variables were present. Apo B increased significantly only in females (p <
      0.05) and Apo Al decreased significantly (p < 0.05) in both sexes when MS was
      present. Adequate metabolic syndrome risk factors criteria, mainly cut-off
      values, need to be defined in the European paediatric population.

PMID- 17217168
TI  - The use of liquid membranes in the multi-residue extraction of stilbenes in a
      variety of biological matrices and their detection with LC-ES-MS.
AB  - Supported liquid membrane (SLM) has been used as a sample preparation method in
      the simultaneous extraction of a mixture of three stilbene compounds in cow's
      milk, urine, bovine kidney and liver tissues matrices. The stilbene compounds
      analysed included, dienestrol, diethylstilbestrol and hexestrol. The liquid
      membrane used for trapping these compounds consisted of 5% tri-n-octylphosphine
      oxide (TOPO) dissolved in di-n-hexylether/n-undecane (1:1). The extraction
      efficiencies obtained after enrichment of 1 ng/L stilbenes in variety of
      biological matrices of milk, urine, liver, kidney and water, ranged from 60 -
      70%, 71 - 86%, 69 - 80%, 63 - 7A% and 72 - 93% respectively. The detection limits
      obtained from urine extraction were 2.1 ng/L, 1.3 ng/L and 3.0 ng/L; from liver
      and kidney tissues were 2.9 ng/L, 1.6 ng/L and 3.8 ng/L and from milk was 3.2
      ng/L, 2.5 ng/L and 4.3 ng/L for hexestrol, dienestrol and diethylstilbestrol
      respectively.

PMID- 17217169
TI  - Determination of Se(IV) and Se(VI) in Italian mineral waters.
AB  - This paper deals with determination of selenium and analysis of its speciation in
      some Italian mineral waters. Selenium was determined by differential pulse
      cathodic stripping voltammetry (DPCSV) even if square wave cathodic stripping
      voltammetry (SWCSV) was also taken into consideration. The selenium determined in
      the mineral waters here investigated is not over 600 ng L(-1); in three samples,
      it was found below the detection limit. Analysis of speciation revealed that
      Se(VI) is the highly prevailing form present: only two of the examined samples
      revealed a detectable amount (few ng L(-1)) of Se(IV). DPCSV made possible to
      detect, in two of the samples, the presence of a specie(s) able to interact with
      Se(IV). The apparent interaction constant for the adduct formation was evaluated
      and the species concentration determined. However, the nature of such compound(s)
      remains unknown.

PMID- 17217167
TI  - The body fat-lowering effect of conjugated linoleic acid: a comparison between
      animal and human studies.
AB  - Different reasons which justify differences between rodents and humans in body
      fat reduction produced by conjugated linoleic acid (CLA) could be proposed. The
      doses used in humans are lower than those used in rodents. Human experiments have
      been performed with CLA isomer mixtures instead of isolated isomers. The variable
      dilution of t-10, c-12, the active isomer, among different preparations might
      explain the reduced responsiveness in humans. Diet composition may modulate CLA
      effects on body fat accumulation. As far as human studies are concerned, a
      specific dietary pattern has not been established. As a result differences among
      studies and also among subjects in the same study are likely. In rodents, the
      effects of CLA vary with genotype, suggesting that genetic predisposition to fat
      accumulation can play an important role in the effectiveness of CLA. Human
      volunteers with different body mass index have participated in the published
      studies and even in the same experiment. So, differences in lipid metabolism
      among subjects could help to explain the discrepancies observed in the
      literature. Age and maturity may also be crucial. Experiments using rodents have
      been conducted with growing animals and there is little evidence of CLA
      effectiveness in adult animals. By contrast, human studies have been performed
      with adults. Inhibition of lipogenesis in white adipose tissue is one of the
      mechanisms which have been proposed to explain the body-fat lowering effect of
      CLA, but lipogenesis in this tissue is very low in humans. Another mechanism
      suggested is increased fatty acid oxidation in the liver associated with
      peroxisome proliferation, but humans are relatively insensitive to this effect.

PMID- 17217170
TI  - Simultaneous determination of thiocyanate and salicylate by a combined UV
      spectrophotometric detection principal component artificial neural network.
AB  - A modified principle component artificial neural network (PC-ANN) model is
      developed for simultaneous determination of thiocyanate and salycilate
      concentration after passing through the bulk of a liquid membrane by tri-phenyl
      benzyl phosphonium chloride. All calibration, and test samples data were obtained
      using UV-Vis spectrophotometer. In this way, a modified PC-ANN consisting of
      three layers of nodes was trained by combination of Bayesian-Levenberg-Marquardt
      as training rule. Sigmoid and liner transfer functions were used in the hidden
      and output layers respectively to facilitate nonlinear calibration. The model
      could accurately estimate the concentration of components with acceptable
      precision and accuracy, for mixtures. The PC-ANN model exhibits a good ability
      for the simultaneous determination of the thiocyanate and salycilate in
      concentration range 0.5 x 10(-4) mol.l(-1) up to 5.0 x 10(-4) mol.l(-1) with Root
      Mean square error (2.22% and 2.20%, for thiocyanate and salycilate, respectively)
      and high correlation coefficients (R2= 0.998 or greater). Results obtained with
      modified trained PC-ANN were compared with stepwise linear regression (SMLR)
      model. Validation of the two models shows a better ability in estimation of the
      modified PC-ANN as compared with the SMLR model (MSRE given are 3.12%, 6.31%.).

PMID- 17217171
TI  - Determination of PAHs in dust from Shanghai by optimized SFE and GC/MS.
AB  - EPA 16 priority polycyclic aromatic hydrocarbons (PAHs) were extracted from dust
      by supercritical fluid extraction (SFE). Parameters (pressure, temperature and
      time) affecting the collection efficiencies of PAHs were assessed according to
      the extraction efficiency, and 30 MPa, 80 degrees C and 30 min dynamic extraction
      time were confirmed to be the best and simplest conditions of SFE to extract 16
      priority PAHs from dust. The characterization of the extracts was carried out by
      gas chromatography with mass detector in selective ion mode (GC/MS/SIM).
      Ultrasonic extraction (USE) was used as a comparison with SFE. The results showed
      that the SFE method has a better efficiency than USE for the extraction of PAHs
      in dust. With the optimized conditions of SFE, the distribution of PAHs in dust
      samples in urban areas of Shanghai from Mar 10, 2005 to May 28, 2005 was
      investigated. The results demonstrated that traffic emission, especially from
      gasoline engines, was the main source of PAHs in dust of Shanghai.

PMID- 17217172
TI  - Preparation and solvent extraction of nickel complex of O,O'
      dinonyldithiophosphate and its application to spectrophotometric determination of
      nickel in sediment samples.
AB  - Nickel complex of O, O'-dinonyldithiophosphoric acid was prepared and
      characterised. Solvent extraction of nickel dinonyldithiophosphate [Ni(DNDTP)2]
      from acidic aqueous solutions into different organic phases was investigated and
      concentration of nickel was determined spectrophotometrically. A simple and
      selective spectrophotometric method was developed and applied to sediment
      samples.

PMID- 17217173
TI  - Solid phase extraction and spectrophotometric determination of trace amounts of
      thiocyanate in real samples.
AB  - A simple, selective and rapid method for solid phase extraction and
      spectrophotometric determination of thiocyanate using a manganese (III) tetrakis
      (p-sulfonatophenyl) porphyrin, [Mn (TPPS) OAC] bound to Amberlite IR-400 has been
      developed. The influence of pH, amount of solid phase, sample matrix, type and
      amount of eluting agent and flow rates i.e. variables affecting the efficiency of
      the extraction system were evaluated and conditions of the sample, eluting
      solution and active phase were optimized. The maximal capacity was found to be as
      1.16 microg mL(-1) for 1200 mL. Thiocyanate ions can be eluted quantitatively
      with 8 mL 0.3 M ferric chloride. The enrichment factor was 150. The linear range
      of the determination is between 0.4-2.0 microg mL(-1) for preconcentration method
      with a limit of detection of 2.8 ng mL(-1). The method has been successfully
      applied for determination of trace amounts of thiocyanate in tap water, saliva
      sample and a synthetic mixture.

PMID- 17217174
TI  - Critical loads for Cd and Pb in the province of Bologna.
AB  - Atmospheric deposition represents a significant source of heavy metals entering
      soil and aquatic ecosystems. The evaluation of their vulnerability can be carried
      out by the Critical Load criterion. In this work we focus the attention on the
      terrestrial ecosystems in the Province of Bologna, estimating the maximum
      tolerable load of cadmium and lead they are able to bear without sustain the
      occurrence of harmful ecotoxicological effects. To this aim the Steady-State Mass
      Balance method is applied on a small scale (10 x 10 Km EMEP grids) and the more
      suitable approach to define critical limits for the Province condition, effect
      base or stand-still, is discussed. The opportunity of simplifying the input data
      collection is also considered, trying to deduce soil properties from geological
      information. Finally, the environmental risk due to the present deposition of Pb
      and Cd on provincial soils is described as exceedances over the critical loads.

PMID- 17217175
TI  - Separation preconcentration method for platinum and rhodium from environmental
      samples using a chelating resin.
AB  - A method of determining trace levels of platinum and rhodium in different samples
      was investigated. The method involves separation and preconcentration of the
      platinum and rhodium from the matrix by flow injection (FI) on-line coupled with
      electrothermal atomic absorption spectrometry (ETAAS) with Zeeman effect
      background correction. Platinum and rhodium were adsorbed on a microcolumn packed
      with 1,5-bis(di-2-pyridyl)methylene thiocarbohydrazide immobilized on silica gel
      (DPTH-gel). The sorbed metals were directly eluted with nitric acid into the
      graphite furnace and determined by AAS.

PMID- 17217176
TI  - Explorative kinetic study on the thermal degradation of five wood species for
      applications in the archaeological field.
AB  - Differential scanning calorimetry (DSC) and thermogravimetric analysis (TG) were
      performed on wood samples of different essences (fir, chestnut, poplar, linden
      and oak) before consolidation. A kinetic analysis was applied on the two-steps
      decomposition processes occurring in all wood samples using either the
      multiheating rates Kissinger equation and the isoconversional Ozawa-Flynn-Wall
      method that enables the variation of activation energy to be determined as a
      function of the degree of reaction. Taking into account both decomposition
      temperature and activation energy for the first degradation step oak seems to be
      the less stable sample. The comparison of DSC curves performed in air with those
      in oxygen enables to consider the role of the partial pressure of oxygen in the
      mechanisms of both decompositions.

PMID- 17217177
TI  - Heavy metals in marine sediments from the Mar Piccolo of Taranto (Ionian Sea,
      southern Italy).
AB  - Heavy metals concentrations (Cd, Cu, Hg, Pb, Sn and Zn) have been determined
      monthly in surface sediments from the Mar Piccolo in Taranto (Ionian Sea,
      Southern Italy. a semi-enclosed marine basin very important from a mussel-culture
      point of view. In sediments, sulphides, percentage of organic carbon and redox
      potential were also determined to show possible correlations between metals
      levels and redox characteristics of marine sediments. Analytical results,
      elaborated by multivariate statistical techniques, confirm that sediments
      collected in the first inlet of Mar Piccolo, where shipbuilding activities are
      present, have a contamination level greater than those collected in the second
      inlet. For each metal, the geoaccumulation index (Igeo) has been calculated as
      criterion to evaluate both pollution levels and metals enrichment in examined
      sediments: Igeo values confirm that the first inlet is an moderately polluted
      area from Hg and Pb. In any case, high sulphide concentrations and negative
      values of redox potentials bring to a conclusion that metals are present in
      sediments, mainly as insoluble sulphides and then as not bioavailable compounds
      for filter feeders organisms such as mussels.

PMID- 17217178
TI  - Bracciano's Lake waters: an experimental survey on the surface layer pollution.
AB  - The chemical and trophic conditions of the surface waters of the lake Bracciano,
      near Roma, have been investigated all through the year 2005. Electrical
      conductivity, pH, alkalinity, hardness, total nitrogen, phosphorus content,
      chloride, fluoride and sulphate ions were measured. The results were compared
      with similar analyses formerly carried out by different authors, to achieve a
      right evaluation of the actual quality of the surface waters of the lake
      Bracciano all over the year 2005.

PMID- 17217179
TI  - Simultaneous determination of arsenic, selenium and mercury in foodstuffs by
      chemical vapour generation inductively coupled plasma optical emission
      spectroscopy.
AB  - A procedure for the simultaneous determination of arsenic, selenium and mercury
      in foodstuffs has been developed. After a two-step microwave-assisted wet
      digestion in closed vessels, using concentrated nitric acid and hydrogen
      peroxide, the solution was analysed by inductively coupled plasma multichannel
      based emission spectrometry using chemical vapour generation as the sample
      introduction system. All steps of the procedure, such as solid sample
      dissolution, pre-reduction to the suitable oxidation state, vapor generation,
      transport and atomization have been designed and optimised taking into account
      the concomitant presence of all the analytes considered. Temporal variation of
      analytical signals as well as interfering effects due to transition elements were
      also studied. Under the optimised operating conditions, the achieved detection
      limits for the simultaneous determination of arsenic, selenium and mercury in
      foodstuffs were 0.006, 0.023 and 0.018 microg g(-1), respectively, allowing their
      determination in real samples. Precision of the analytical procedure was 6.8% for
      arsenic, 5.2% for selenium and 7.7% for mercury (n=7). The accuracy and
      reliability of the method was verified by the analysis of both standard reference
      materials (rice flour and spinach leaves) and real samples (natural and Se
      enriched rice).

PMID- 17217180
TI  - Good work for dentists--ideal and reality for female unpromoted general practice
      dentists in a region of Sweden.
AB  - Female unpromoted general practice dentists (GPDs) in the Public Dental Health
      Service (PDHS) constitute about one fourth of all working dentists in Sweden.
      Unpromoted means that the position is without managerial functions. According to
      many reports, they have a problematic psychosocial work situation. THIS THESIS
      AIMED TO: Describe the perceived health for these GPDs, in comparison with others
      with a similar work situation. Analyse their sense of support in comparison with
      others. Describe how they perceived "good work", i.e. both the healthy and
      socially responsible work, and whether there was a difference between their ideal
      and their reality. Analyse patterns in two aspects - the moral and the career
      aspects - of "good work" for dentists. In zooo, questionnaires were sent to all
      female unpromoted GPDs in the PDHS in a region of Sweden. The response rate was
      94%. RESULTS: The dentists felt unwell, worse than other compared groups. There
      was little support from the management. There was little inter-colleague contact.
      There was no cross-sectional assciation between collegial neworks and support,
      but the qualitative investigation showed that collegial networks were perceived
      as positive. There was a great difference between ideal and reality concerning
      good work. The dentists felt a lack of influence, and this was the greatest
      difference of all. Three components of good work - "moral values and skill
      discretion", "career development" and "work environment" were found. The dentists
      emphasized the moral basis of their work, confirming the character of dentistry
      as primarily human service work. IN CONCLUSION: There were serious work
      environmental problems among these dentists. The dentists felt unwell and felt a
      great lack of influence on important decisions. There was little inter-colleague
      contact, but collegial networks were perceived as positive. There was little
      support from the management, indicating a clear weakness in the relations between
      employers and female unpromoted GPDs in the PDHS. Three components of good work
      were found, where the moral component was the most important but it also showed
      the greatest difference between ideal and reality. Thus, the dentists emphasized
      the moral basis of their work, confirming the character of dentistry as primarily
      human service work and not industrial work. The dentists with the highest level
      of commitment perceived the largest differences. The PDHS organization has
      therefore failed to convince or engage those whom it ought to engage, i.e. those
      with the greatest commitment. The way to improve the female unpromoted GPDs' work
      situation would be through increased influence and support, bridging the gap
      between ideal and reality.

PMID- 17217181
TI  - [The normative concept of guilt in criminal law between freedom of will and
      neurobiological determinism].
AB  - To make criminal conduct liable to punishment, criminal responsibility, defined
      as individual blameworthiness in terms of social ethics, is required as point of
      reference--both to create and limit the state's right to punish the offender.
      Neurobiological findings and more recent investigations in brain research have
      given rise to serious doubts regarding this "conditio sine qua non" of the
      state's power monopoly. As a result of preceding unconscious decisions, so the
      argument goes, Man is not free in his will, and the normative principle of
      culpability would need to be relinquished in favour of a "law of measures"
      detached from guilt. A detailed analysis of the underlying experimental setups,
      in particular the investigations by Benjamin Libet involving the measurement of
      the readiness potential, has shown, however, that the results of the test methods
      do not justify the demand for a profound change up to the point of a total
      revision of criminal law, and that they cannot invalidate the concept of freedom
      of will apostrophised on principle. The empirical data obtained fail to
      demonstrate if and why decisions of the will should not be free, the more so as
      the nomothetic method used ignores completely the idiographic understanding and
      interpretation of the always context-related and socio-structurally (pre)-moulded
      personality of the offender. Performed in a laboratory setting as individual
      actions with a comparatively simple structure and unrelated to a concrete
      situation, they can by no means be translated to the (more) complex situation
      under which an offence is committed including the decision-making processes
      determined by psychodynamic, motivational and intentional aspects as well as
      highly specific reciprocal interactions within the offender-victim constellation.
      Even if these experiments had shown the determined nature of human decisions,
      they would not necessarily have to bring about a conceptual change of paradigms
      of the normative concept of guilt, because as a result of self-attribution, the
      intra- and inter-subjective experience of the freedom of will renders the mere
      "illusion of freedom" sufficient to assign to an individual the appropriate sense
      of responsibility, which is also accepted by him. The alternative of a law of
      measures independent of guilt and culpability must be rejected because it is
      incapable of instituting sufficient protection, both in qualitative and
      quantitative terms, against prognostically diffuse and utilitarian hypertrophied
      prophylactic efforts on the part of the state up to the point of a revolutionised
      anthropological design, as shown quite clearly by the repressive and restrictive
      tendencies apparent in criminal policy since 11 September 2001. Consequently, the
      classic principle of guilt as one of the humanitarian foundations of punishment
      imposed by the state needs to be protected and upheld in the face of rash and
      inadequately considered law amendment endeavours. With its principles having
      slowly grown over the ages under democratic consent, criminal law is capable of
      immunising itself against uncritically generalised restructuring attempts based
      on inductive false conclusions and the confusion of coincidence, correlation and
      causality, let alone against the neurobiological "occupation tendencies" of
      normative premises. Regardless of their undeniable fascination, future brain
      research activities and the respective findings in the neurobiology of thinking,
      decision-making and acting as an indispensable empirical and epistemological
      starting point must always be reviewed in terms of their factual and normative
      implementation powers in favour of or against the human freedom of will.

PMID- 17217182
TI  - [Homicides in East Berlin from 1980 to 1989. Part I: victimology and
      phenomenology].
AB  - At the Institute of Legal Medicine of the Humboldt-University in Berlin 8,580
      autopsies were carried out in the period of analysis from 1980 to 1989 -
      including 139 homicides (= 1.6 %). The first part of this study deals with the
      victim-related analysis. Furthermore, the criminologically relevant aspects of
      the phenomenology of crime are described. Apart from the low frequency, the
      mainly short latency period and the low rate of homicides with removal of the
      victim are noteworthy.

PMID- 17217183
TI  - [Aggression homicide and rejection homicide: a communicative classification of
      homicide].
AB  - Based on a 10-year sample of homicides (n = 50), the hypothesis was tested that
      it is possible to differentiate between aggression and rejection homicide. The
      aggression homicide results from the offender/victim relationship, which is no
      longer accepted for some reason. In contrast, in the rejection homicide the
      offender radically strives for a goal which can only be reached if the victim is
      eliminated. Based on forensic-psychiatric expert opinions (n = 50), the case
      analyses yielded 31 aggression homicides and 18 rejection homicides, one case
      could not be classified. Aggression homicides differed significantly from the
      rejection homicides with regard to their main motives. Hate in quarrel (n = 8),
      violent occupation of the victim (n = 7), delusions (n = 5), revenge (n = 3),
      self-defence (n = 2), and jealousy (n = 1) characterized the aggression
      homicides, whereas rejection homicides were dominated by economic motives (n =
      14). Two offenders intended to get rid of the victim and one offender wanted to
      rescue a third person. From a forensic-psychiatric point of view, the pertinent
      statistical data (social data, diagnosis, criminal responsibility) are reported
      and the significance of the differentiation between aggression homicide and
      rejection homicide for medico-legal or criminological case profiling and for the
      prognosis of the risk potential is discussed.

PMID- 17217184
TI  - Training for terrorism-related conditions in hospitals: United States, 2003-04.
AB  - OBJECTIVE: This study estimates baseline data to determine which hospital
      characteristics are associated with providing terrorism preparedness training to
      clinical staff. METHODS: Information from a Bioterrorism and Mass Casualty
      Supplement to the 2003 and 2004 National Hospital Ambulatory Medical Care Surveys
      was used to provide national estimates of variations in terrorism preparedness
      training by eight hospital characteristics. Of 874 hospitals in scope, 739 (84.6
      percent) responded. Estimates are presented with 95 percent confidence intervals.
      RESULTS: Hospitals with Joint Commission accreditation were more likely to
      provide terrorism preparedness training to all types of clinical staff (staff
      physicians, residents, nurse practitioners, physician assistants, and laboratory
      staff). Teaching hospitals, medical school affiliation, bed capacity, and urban
      location were also associated with training staff physicians, residents, nurse
      practitioners, and physician assistants. Hospitals with residency programs were
      associated with training only staff physicians and residents. There was more
      parity across hospital characteristics in training nurses and laboratory staff
      than for physicians, residents, nurse practitioners, and physician assistants.
      Joint Commission accreditation was the most consistent factor associated with
      providing training for all nine exposures studied (smallpox, anthrax, chemical
      and radiological exposures, botulism, plague, tularemia, viral encephalitis, and
      hemorrhagic fever).

PMID- 17217185
TI  - Nutritional surveillance in Tuscany: eating habits at breakfast, mid-morning and
      afternoon snacks among 8-9 y-old children.
AB  - INTRODUCTION: The prevalence of overweight and obesity in children is rapidly
      increasing in many countries. For that it has been interesting to investigate the
      eating habits of 8-9 y-old Tuscany children by paying attention to their meals
      frequency per day and their food choices in total and in relation to children's
      Body Mass Index (BMI) classes. In addition we considered some environment factors
      that could affect the children eating behaviours, such as mother's BMI and their
      education level. METHODS: A statistical sample of 3076 (1583 males, 1493
      females), 8-9 year-old school-children was collected; weight and height were
      measured using standardized personnel and instruments. BMI classes were
      calculated using Cole et al.'s cutoff for children and adolescents. In order to
      evaluate the consumption frequency of individual meals and various foods, a Food
      Frequency Questionnaire (FFQ) was used, which was completed by the children
      themselves at school. A self-administered questionnaire revealed the weight and
      height of parents and their educational levels. Three educational levels were
      established: high, medium and low. RESULTS: The results showed that 92.3% of
      children ate breakfast from 4-7 times a week, the vast majority at home, while
      only 3% declared consuming breakfast never or almost never The most preferred
      breakfast consisted of milk and biscuits for all children's BMI classes. 95.9% of
      children reported having midmorning snack at school; fruit juice and tea are the
      most frequently consumed liquid foods, and pizza, salami sandwiches and pre
      packaged snacks are the most frequently consumed solid foods in all BMI classes.
      93.6% ate afternoon snack for the most part at home, even if 12% of children
      reported consuming it elsewhere; fruit juice and tea with pizza, sandwiches and
      pre-packaged snacks are still the most highly consumed foods by all children's
      BMI classes. The consumption frequency of breakfast (P < 0.001), mid-morning (P <
      0.05) and afternoon snack (P < 0.05) of 8-9 y-old Tuscany children decrease with
      increase the children's BMI classes. The same tendency may be noted for the
      consumption frequency of breakfast in relation to mother's BMI (P < 0.05) and
      their education level (P < 0.05). This data strengthens the thesis that some home
      environments can affect the children's eating behaviours. CONCLUSION: No
      substantial differences in food choices at the meals analyzed were determined
      among normal weight, overweight and obese children. Children of normal weight had
      a greater tendency to consume meals more regularly. Mother's BMI and their
      education level can have influence on children's eating behaviours.

PMID- 17217186
TI  - Bioinformatics and microbial biodiversity: analysis of vibrios by the GenEnv
      system.
AB  - Sequence-based approaches to prokaryotic systematics and typing represent a
      modern and promising strategy in epidemiology and environmental microbiology.
      GenEnv, a database-driven system for bacterial typing, was developed in order to
      provide user friendly tools for supporting biomolecular analysis of bacteria. The
      family Vibrionaceae represents a heterogeneous taxon of aquatic microrganisms,
      harbouring a plethora of genomes currently analyzed by different molecular
      techniques. Under the query "Vibrio", GenEnv retrieved 256 organisms, included in
      a total number of 19 families. Overall, 548 sequences, comprising 16S rRNA
      (n=402), rpoB (n=1), gyrB (n=145) were available. In addition, GenEnv system
      allowed primer design, homology analysis and restriction maps, for immediate
      applications to the study of Vibrionaceae.

PMID- 17217187
TI  - Microbiological surveillance of hospital ventilation systems in departments at
      high risk of nosocomial infections.
AB  - The air in hospital wards with patients at high risk (Surgeries, Intensive Care
      Units and Bone Marrow Transplant Centers) has been surveyed less than the one in
      Operating Rooms. Therefore in this study we considered useful to verify the
      microbic contamination of the air of those wards evaluating the consistency of
      ventilation systems in relation also to the presence and location of HEPA
      absolute filters. Seven departments of Genoese San Martino Hospital at high risk
      of infection were taken into account. In there, environmental investigations have
      been performed by air samplings and by analyzing bacterial and fungal growth on
      plates after an incubation period. Almost 60% of all samples taken in wards
      yielded a positive result and the average values of bacterial and aspergillar
      charges measured at air flow emission openings decisively exceed the ones
      considered standard in operating rooms. Still, the average values of airborne
      bacterial charges were significantly higher in those wards equipped with central
      filters (p < 0.001), while as far as the aspergillar charge is concerned, no
      statistically relevant differences were noticed. In wards with ventilation
      system, the bacterial charge value raises from the emission grids to the middle
      of the room and to the aspiration grids, while the ward not equipped with a
      ventilation system presents in the middle of the room an average bacterial charge
      2 to 10 times higher than the one in other wards. The average values regarding
      bacterial and aspergillar charges resulted quite high in all the departments
      surveyed. Nevertheless, if we take into account ventilation systems equipped with
      absolute filters HEPA located centrally or peripherally, it can be outlined that
      the air quality from the point of view of both microbic and aspergillar
      contamination turns out to be decisively better in systems with peripheral
      filters. Moreover, a compared analysis of the three Hematology wards allows us to
      infer that the presence of artificial ventilation systems can lower the bacterial
      and fungal compared with a ward with natural ventilation.

PMID- 17217188
TI  - Study on hepatitis B and C serologic status among municipal solid waste workers
      in Messina (Italy).
AB  - A study on hepatitis B and C virus seroprevalence was carried out on blood
      samples from 327 municipal solid waste workers in Messina (Italy) to verify the
      hypothesis that this category of workers is at high risk for such diseases. The
      fact that 32.41% of all the subjects showed previous exposure to hepatitis B
      virus (HBV) substantiates the need to proceed with compulsory HBV vaccine
      prophylaxis in this category of workers, also in anticipation of possible medical
      legal litigations.

PMID- 17217189
TI  - Review on significance debate.

PMID- 17217190
TI  - Nosocomial candida infections: epidemiology of candidaemia.

PMID- 17217191
TI  - [Risk factors and complications in orbital surgery, their preventive measures].
AB  - Based on the experience in surgically treating 2300 patients with different
      pathological orbital processes, the author formulates risk factors of possible
      postoperative complications. These include primarily the form and size of the
      osseous orbit, no precise information on the topometry of an orbital lesion
      focus, and inadequate choice of a surgical approach. Postoperative complications
      are analyzed and evaluated. A role of consideration of risk factors and the
      application of new technologies using microsurgical techniques is shown to reduce
      the frequency of complications, late ones in particular.

PMID- 17217192
TI  - [Orbital hernias: new views of the pathogenesis, possibilities of correction].
AB  - The paper deals with the basic pathogenetic aspects of development of orbital
      hernias--the factors of a tarsoorbital fascial change in the presence of the
      hereditary syndrome of connective tissue hyperplasticity and elevated
      intraorbital pressure, which affects the volume of orbital fat. The possibilities
      of a differential diagnosis of orbital hernias and eyelid edemas are considered.
      There is a biomechanical association of orbital hernias with acquired age-related
      enophthalmos. The examples of impairments in the tolerance of the optic nerve and
      in the development of optic neuropathy in enophthalmos are considered. The fact
      that there may be tarsoorbital fascial lesions, followed by the development of
      orbital hernias after parabulbar injections is indicated. The author proposes an
      operation dealing with the reposition of orbital hernias instead of their
      resection during blepharoplastic interventions.

PMID- 17217193
TI  - [Current approaches to surgical treatment for cranioorbital injuries].
AB  - A hundred and two victims (120 reconstructive operations) with cranioorbital
      injuries were operated on at the N. N. Burdenko Institute of Neurosurgery in
      different periods after injury in 2000 to 2005. In 69 (67.6%) of the 102 patients
      (82 operations) bone autografts, mainly calvarial ones (61 operations in 55
      victims), were used. The operations were performed, by utilizing both
      neurosurgical and ophthalmoplastic techniques and up-to-date craniofacial
      surgical procedures. The basic principle of surgical treatment for cranioorbital
      injuries was three-dimensional orbital anatomy restoration, such as the
      stabilization and repair of the orbital rim and one-stage reconstruction of the
      afflicted walls. Computed tomography provides main information for the efficient
      planning of a surgical intervention. Optimal cosmetic and functional results are
      attained when primary reconstructive surgery is made in the acute or early (10-14
      days) periods after injury. Secondary cranioorbital reconstructive surgery may be
      performed in one or several steps in relation to the severity and signs of bone
      structural injuries and to the state of soft tissues. A bone autograft is the
      material of choice for repair of all portions of the cranioorbital region.

PMID- 17217194
TI  - [Ultrasound spatial clinical analysis of the orbital part of the lacrimal gland
      in health].
AB  - The paper presents an algorithm of ultrasound spatial analysis of the unaltered
      lacrimal gland. The algorithm has been used to define its shape, size, density,
      structural features and the pattern of blood supply, as well as the anatomic and
      topographic position in the orbit. The study was conducted in the B- and 3D-modes
      of color and energy Doppler mapping on both sides. The procedure was based on the
      clinical examination of 40 healthy individuals aged 20 to 75 years who had no
      systemic vascular and lymphoid tissue lesions or functional impairments of the
      lacrimal gland itself. The study defined the mean values of the ultrasound
      section of the lacrimal gland: 1-1.8 and 0.5-0.8 cm for vertical and horizontal
      ones, respectively; the mean volume of the lacrimal gland of 0.66 to 1 cm(3) and
      the densitometric parameters (density and vasculogenicity index); three types of
      structural manifestations of the unaltered lacrimal gland were identified. The
      proposed algorithm of ultrasound study of the lacrimal gland may enhance the
      accuracy and validity of results in the differential diagnosis of various orbital
      diseases.

PMID- 17217195
TI  - [Computed tomographic signs of extraocular muscle changes in endocrine
      ophthalmopathy].
AB  - The paper presents the results of a computed tomographic study of extraocular
      muscles (EOM) in 75 patients (131 orbits) without orbital pathology and different
      forms of endocrine ophthalmopathology. It also gives data on changes in EOM
      density and structure. The outline of the muscles has been studied at different
      stages of edematous exophthalmos and endocrine myopathy. The obtained
      quantitative results of EOM changes allow one to make a differential diagnosis of
      different forms of endocrine ophthalmopathy and to plan treatment of these
      patients.

PMID- 17217196
TI  - [Systemic enzyme therapy in the treatment of children with lower orbital wall
      fractures].
AB  - Wobenzim, a drug for systemic enzyme therapy, was used in 26 children with lower
      orbital wall fractures as monotherapy in early periods (on days 1 to 7) after
      brain injury to improve healing conditions and to minimize the formation of scar
      tissues in the fractural area. A control group comprised 24 patients who received
      systemic dehydration and vessel-strengthening therapy. Systemic enzyme therapy
      with Wobenzim could reduce the attenuation time of inflammatory manifestations of
      injury, prevent complications, such as strangulation of the musculus rectus
      inferior in the fractural area and development of strangulated orbital soft
      tissue hernia, and substantially decrease the number of patients having
      indications for surgical plastic repair of the orbital wall, as compared with the
      control group.

PMID- 17217197
TI  - [Rehabilitation of patients with unilateral congenital microphthalmos].
AB  - The purpose of the present study was to develop a surgical treatment for
      congenital microphthalmos, by using the biomaterial Alloplant that causes an
      increase in eyeball sizes. There were 48 cases of unilateral congenital
      microphthalmos prior to surgery. The patients' age ranged from 2 to 14 years; the
      duration of follow-ups was 1 to 6 years. Data processing by parametric variance
      analysis indicated that there was an increase in the mean sizes of the
      anteroposterior and transverse axes (APA and TA) of the eye 2-3 years following
      surgery. With the use of the authors' method, the conjunctival cavity is not
      deformed and, on the contrary, after surgery it acquires a regular slit-like
      shape with vaults of sufficient depth, which upgrades the quality of prosthetic
      repair in future. The increases in the sizes (APA and TA) and volume of the
      eyeball not only just after surgery, but also in the late periods (up to 2-3
      years) suggest that the developed operation using the biomaterial Alloplant
      triggers the mechanism of coordinated eyeball growth.

PMID- 17217198
TI  - [Early postcontusion eyeball circulation as evidenced by color Doppler mapping].
AB  - Early postcontusion hemodynamic disorders were studied, by analyzing the results
      of color Doppler mapping. The study included patients aged 10 to 45 years with
      moderate and severe postcontusion retinal changes and a visual acuity of 0.8 to
      0.01. Color Doppler mapping was used to visualize blood flow in the ophthalmic
      artery, central retinal artery, and posterior short ciliary arteries. Preliminary
      studies revealed circulatory changes in the ophthalmic arterial system in the
      early postcontusion period. In severe macular and optic nerve lesions, a
      significant reduction in blood flow was detectable in all the vessels under
      study, but there was its more pronounced reduction in the central retinal artery
      and posterior short ciliary arteries, which directly corrected with the found
      retinal changes since these arteries are the only source of retinal circulation.

PMID- 17217199
TI  - [Systemic autoantibodies and their correction in patients with diabetic
      retinopathy in type 1 diabetes mellitus].
AB  - Examination of 91 patients with diabetic retinopathy in the presence of type I
      diabetes mellitus (DM-1) showed that 56% of the patients had a great variety of
      organ-specific and organ-nonspecific autoantibodies (AABs), including those to
      the microsomal and cytoplasmic fractions of endocrine glands, such as pancreas,
      thyroid, and pituitary. AABs were most common to the pituitary (23.2%), total
      myelin protein (18.7%), and denatured DNA (17.6%). There were correlations
      between AAB and the duration of DM-1 more than 20 years (78.3%; p < 0.05),
      between the total myelin protein AAB and encephalopathy (31.3%; p < 0.05),
      between the denatured DNA AAB and the increased retinal vascular permeability
      (29.3%; p < 0.05), which suggests their implication in vascular wall
      disintegration. No correlations could be found between AAB to the pituitary,
      pancreas, and thyroid and obvious pathology of the glands. Combined therapy with
      the immunomodulators thymactid and lycopide yielded a total beneficial effect
      (AAB disappearance, decreased titers, and no changes) in 88.3% of case while
      beneficial effect of insulin therapy was obtained in 53.9% of cases, which
      suggests that it is expedient to include of currently available immunomodulators
      into traditional insulin therapy.

PMID- 17217200
TI  - [Hyper-IGE reactions in uveitis and their immunomodulation with cytokine
      containing agents].
AB  - Examination of 73 patients with primary, active uveitis of various etiology
      established a high frequency (78%) of IgE hyperconcentrations particularly among
      patients with viral uveitis (95%) and in the presence of systemic diseases
      (65.2%). The correlations between IgE and some values of T, humoral immunity, and
      cytokines support the multiple factors of the immunopathogenesis of uveitis.
      Combined treatment with local instillations of autocytokines and superlymph
      provided a high immunomodulating effect. The established IgE hyperproduction in
      uveitis may be a reflection of either rapidly progressive allergy or an allergic
      background and serve as a pathogenetic rationale for the use of antihistamines
      and immunotherapy with cytokine-containing agents.

PMID- 17217201
TI  - [Specific features of manifestation of anterior optic tract gliomas in patients
      with type 1 neurofibromatosis: ophthalmological and neurovisualizational
      aspects].
AB  - Gliomas of the anterior optic tract (AOT) (optic nerves, chiasms, and visual
      tracts) are benign slowly growing tumors usually detectable in childhood. These
      are a rather heterogenic group of tumors. The pattern and course of the disease
      are frequently affected by the presence of type 1 neurofibromatosis (NF-1) in the
      patient. The ophthalmological symptoms of AOT lesion in the presence of NF-1 were
      analyzed in 80 patients aged 1 to 24 years (median 5 years). According to the
      ophthalmological symptoms and the pattern and extent of lesions to AOT
      structures, the authors identified 4 groups by the data of neurovisualization
      techniques (magnetic resonance imaging, computed tomography) and revealed that
      the ophthalmological pattern reflected the site and degree of lesion to AOT
      structures. At the same time it is shown that there is a group of silent tumors
      attending without visual disorders. These tumors have the similar
      neurovisualization pattern, such as a moderate thickening of AOT structures and
      they occur in 13.8% of cases, as shown by the authors.

PMID- 17217202
TI  - [A follow-up of patients with anterior optic tract glioma concurrent with type 1
      neurofibromatosis].
AB  - Fifty-nine patients with anterior optic tract (AOT) lesion concurrent with type
      neurofibromatosis (NF-1) were followed up for 1 to 36 years (median 5 years).
      Based on the study, the authors identified several grades of the disease: -
      stabilization without intervention; - stabilization after treatment; -
      insignificant negative changes as a slight tumor growth and a further
      stabilization of the process; - occasionally negative changes irrespective of
      treatment. The behavior of a tumor is unpredictable. The onset of progression in
      infancy is a poor predictor. Ophthalmological symptoms are not the criterion that
      can be used to make a prognosis. The prognosis is largely determined by
      neurovisualization techniques and primarily magnetic resonance imaging. A uniform
      slight thickening of AOT structures irrespective of the extent of the process
      along the AOT should be referred to as a good prognosis. There was no spontaneous
      tumor regression in any case. By taking into account the beneficial effect of
      radiotherapy, the authors consider it expedient to use it as monotherapy and in
      combination with surgery. Bypass surgery on the spinal fluid system frequently
      fails to entirely solve the problem intracranial hypertension.

PMID- 17217203
TI  - [Effects of nootropic agents on visual functions and lacrimal antioxidative
      activity in patients with primary open-angle glaucoma].
AB  - The paper presents the results of an investigation of the effect of the nootropic
      agents pantogam and nooclerine on visual functions in patients with primary open
      angle glaucoma. These agents have been found to have a beneficial effect on the
      functional activity of the retina and optic nerve, light sensitivity, hemo- and
      hydrodynamics of the eye.

PMID- 17217204
TI  - [Anterior ischemic neuropathy associated with antiphospholipid syndrome].

PMID- 17217205
TI  - [A case of iridic leiomyoma].

PMID- 17217206
TI  - [A case of choroidal leiomyosarcoma].

PMID- 17217207
TI  - [Pathogenesis of age-related macular degeneration].

PMID- 17217208
TI  - [Analysis of the prevalence of diseases of the eye and appendages among the adult
      rural population of the Lipetsk Region on the basis of the data of health
      monitoring].

PMID- 17217209
TI  - Immunoglobulin concentration in gingival tissue of type 2 diabetic patients with
      periodontitis.
AB  - BACKGROUND: Diabetes mellitus is considered as a risk factor for the initiation
      and progression of periodontal disease. The diabetic patients often exhibit
      decreased immune response and increased susceptibility to infection. In the
      present study, a quantitative estimation of the gingival tissue immunoglobulin
      concentrations in diabetic and non diabetic subjects with periodontitis was
      assessed and compared with that of clinically healthy gingiva. METHOD: 40
      gingival tissue samples obtained from 20 diabetic (Type 2) and 20 non-diabetic
      subjects were subjected to quantitative estimation of immunoglobulins G, A, and
      M. The data thus obtained were compared to the level of immunoglobulin found in
      clinically healthy gingiva. RESULTS: The IgG and IgA level in the tissues of both
      diabetic and non-diabetic subjects with periodontitis were found to be
      significantly higher than that of healthy subjects. The diabetic group also
      showed a significantly higher IgG and IgA levels compared to the non-diabetic
      group with periodontitis. CONCLUSION: These findings support the concept that the
      humoral immune response plays an important role in the pathogenesis of
      periodontal disease in diabetics. The significantly higher levels of
      immunoglobulin in the gingival tissues might be a protective mechanism against
      the increased bacterial challenge in diabetic subjects.

PMID- 17217210
TI  - Evaluation of three topical anaesthetic agents against pain: a clinical study.
AB  - AIM: To compare pain responses of children during local anaesthetic infiltration
      at bilateral buccal sites prepared with topical application of EMLA 5% cream,
      benzocaine 18% gel or lignocaine 5% ointment and also to find out the rapidity of
      onset of action of these agents. METHODS: 60 healthy children aged 6 to 12 years
      old, received bilateral buccal infiltration following application of topical
      anaesthetic agents applied in a double blind design. Pain responses were compared
      based on subject self report using visual analogue scale (VAS) and operator
      assessment using Sound -Eye -Motor (SEM) scale. RESULTS: Benzocaine gel had the
      rapidest onset of action. EMLA 5% cream proved to be superior in pain reduction
      compared to benzocaine and lignocaine. Taste acceptance was better with
      benzocaine gel. Further studies are required for EMLA cream with an improved
      formulation more suitable for mucosal application before its routine use in
      dentistry.

PMID- 17217211
TI  - Expression of matrix metalloproteinases (MMP-1, MMP-2 and MMP-9) and their
      inhibitors (TIMP-1 and TIMP-2) in oral submucous fibrosis.
AB  - Immunohistochemical staining of formalin fixed, paraffin embedded tissue sections
      of OSF for MMPs-1,2,9 and their tissue inhibitors TIMP-1and 2 was performed using
      monospecific antibodies coupled with gelatin zymography (MMP-2 and 9) for
      measuring enzymatic activity quantitatively and for distinguishing the active
      from the inactive variants of enzymes. The present study, contrary to earlier
      reports, recorded statistically significant increase in the levels of stromal
      expression of MMP-1, MMP-2 and MMP-9 and TIMP-1 and TIMP-2 using monospecific
      antibodies reacting against tissue antigens. The simultaneous increase in
      reactivity of MMPs and TIMPs poise difficulty in interpretingthe results of this
      study. The possible reasons for this result, against the backdrop of existing
      knowledge, were attempted in this study.

PMID- 17217212
TI  - Toothbrush selection: a dilemma?
AB  - The toothbrush is a fundamental tool used for accomplishing plaque control.
      Various types of toothbrushes available in the market keep the buyer in a state
      of dilemma as to which one to choose, due to lack of information about the
      "quality" of it. This study has been designed to understand whether all the
      products available in the market adhere to the specifications laid down by the
      ADA, which is universally accepted in standardization of a tooth brush. 95% of
      the brushes surveyed contain less number of bristles per tuft than specified and
      a large percentage deviate from the standard prescribed value for their bristle
      diameter and other dimensions. Few brushes labeled as "Soft" were "Medium" and
      labeled "Medium" were "Hard". The study will bring to light the quality of
      toothbrushes available in India for a rationalised selection of appropriate
      toothbrush by the community at large.

PMID- 17217213
TI  - Oral health status and treatment needs in institutionalized psychiatric patients:
      one year descriptive cross sectional study.
AB  - BACKGROUND AND OBJECTIVES: Psychiatric patients are one of the special groups
      requiring attention as they are often neglected. Oral health is an major
      determinant of general health for psychiatric patients and may have a low
      priority in the context of mental illness. The present study was conducted to
      assess the oral health status and treatment needs of institutionalized
      psychiatric patients of Davangere. METHODS: 220 psychiatric patients admitted in
      two general hospitals of Davangere during the period of one year were included in
      the study. The oral health status was evaluated with respect to caries, oral
      hygiene, and periodontal status. RESULTS: Of the 180 examined with the response
      rate of 81.8%. 58.3% were males, mean age was 36.7 years, 57.8% had < 1 year of
      mental illness with a mean of 2.2 years, and 90% were self-sufficient. The
      multiple logistic regression analysis showed that the mean DMFT (0.92) increased
      with age, duration of mental illness, and irregularity of oral hygiene habits
      (P<0.001). Mean OHI-S score was 3.3 and multiple logistic regression analysis
      showed that the mean OHI-S score increased with age (P<0.001). The multiple
      logistic regression analysis showed that the CPI score increased with age,
      duration of mental illness, and degree of helplessness (P<0.001). INTERPRETATION
      AND CONCLUSION: The findings of this study demonstrates low caries prevalence,
      poor oral hygiene, and extensive unmet needs for dental treatment.

PMID- 17217214
TI  - Dentinal hypersensitivity?--Can this agent be the solution?
AB  - AIM: To test the efficacy of desensitizing tooth paste containing EMS salts in
      alleviating dentinal hypersensitivity, reducing plaque accumulation, and reducing
      gingivitis. METHODS: A randomised, single blind, parallel placebo controlled
      study was conducted in 40 cases. The cases were randomly assigned to test and
      control groups. The test group was instructed to use the test tooth paste
      (containing EMS salts) and control group a placebo tooth paste (without any
      therapeutic agents) for a period of 6 weeks. The hypersensitivity levels were
      measured with scratchometer and verbal rating scale. Student t test and
      wilcoxon's Mann-Whitney test were used to compare the test and control groups.
      RESULTS AND CONCLUSION: The results indicated that both the test as well as the
      control toothpastes were effective in alleviating dentinal hypersensitivity as
      well as reducing gingivitis. However, the test toothpaste was superior in
      alleviation of dentinal hypersensitivity.

PMID- 17217215
TI  - Dental arch dimensions in primary dentition of children aged three to five years
      in Chennai and Hyderabad.
AB  - OBJECTIVE: The purpose of this study was to assess the arch dimensions in primary
      dentition of 3-5 years old children in Chennai and Hyderabad. As no primary to
      the mixed dentition and determining the existence of sexual dimorphism. METHODS:
      Children were selected fro various schools of both Chennai and Hyderabad, with
      complte set of primary dentition. Study casts were made and measurements of arch
      dimensions were made using digital sliding calipers. The data obtained was
      subjected to statistical analysis. RESULTS: The mean values and standard
      deviations of the various arch dimensions are given in the tables. CONCLUSION:
      Generally boys exhibited a greater arch dimensions than girls in both groups.
      Some of the dimensions showed a statistically significant mean values.

PMID- 17217216
TI  - Pentoxifylline therapy: a new adjunct in the treatment of oral submucous
      fibrosis.
AB  - OBJECTIVE: This study was designed to determine the effect of pentoxifylline
      (Trental) on the clinical and pathologic course of oral submucous fibrosis. This
      drug is a methylxanthine derivative that has vasodilating properties and was
      envisaged to increase mucosal vascularity. STUDY DESIGN: This investigation was
      conducted as a randomized clinical trial incorporating a control group (Standard
      drug group SDG, multivitamin, and local heat therapy) in comparison to
      pentoxifylline test cases (Experimental drug group EDG, 400mg 3 times daily, as
      coated, sustained release tablets). The stipulated treatment period was 7 months
      and a total of 29 cases of advanced fibrosis (14 test subjects and 15 age and sex
      matched diseased controls) were included in this study and 100% compliance was
      reported at the end ofthe test period. RESULTS: Mild gastric irritation that
      could be managed by diet protocols was the only untoward symptom reported during
      this trial. Review of the patients and controls was done at an interval of 30
      days and subjective and objective measurements were recorded. The follow up data
      at each visit with respect to each other and to base-line values was calibrated
      using a nonparametric test of Mann-Whitney (Kruskal-Wallis test). Significant
      comparisons with regard to improvement were recorded as objective criteria of
      mouth opening (t=11.285, p= 0.000), tongue protrusion (t= 3.898, p = 0.002), and
      relief from perioral fibrotic bands (p = 0.0001554). Subjective symptoms of
      intolerance to spices (p = 0.0063218), burning sensation of mouth (p =
      0.0005797), tinnitus (p=0.000042), difficulty in swallowing (p=0.0000714). and
      difficulty in speech (p=0.0000020) were also recorded significant improvement at
      the end of the trial period. CONCLUSION: This pilot investigation points to the
      effectiveness of pentoxifylline as an adjunct therapy in the routine management
      of oral submucous fibrosis.

PMID- 17217217
TI  - Extragingival pyogenic granuloma.
AB  - Pyogenic granuloma is a well-known localized granulation tissue overgrowth in
      reaction to mild irritation. Although it is known to show a striking predilection
      for the gingiva, it can be found extragingivally with varying clinical features
      that sometimes may mimic more serious lesions such as malignancies. The clinical
      diagnosis of such an uncommon extragingival pyogenic granulomra can be quite
      challenging. The purpose of this article is to report an unusual case of
      extragingival pyogenic granuloma occurring on the lower lip, which presented as a
      cutaneous horn.

PMID- 17217218
TI  - Tuberculous ulcer of tongue with oral complications of oral antituberculous
      therapy.

PMID- 17217219
TI  - [G. V. Khlopin and cotemporary aspects of occupational medicine: sources,
      parallels, prospects].

PMID- 17217220
TI  - [Evidence-based medicine in occupational health: principles and evaluation of
      work and health relatedness].
AB  - The article deals with essentials of evidence-based medicine, its principles in
      occupational medicine and patterns of evaluation of occupation and disease
      relatedness. The authors suggest an algorithm of medical examinations considering
      evidence-based medicine principles.

PMID- 17217221
TI  - [Studying chronic effects caused by alkaline products of from bituminous-salt
      masses obtained through destruction of sarin, soman and RVX].
AB  - The authors summarized study results on chronic effects caused by products of
      leaching from bituminous-salt masses obtained through destruction of sarin, soman
      and RVX. State of experimental rats was evaluated with integral informative tests
      (physiologic, biochemical, hematologic and morphologic) presenting changes in
      objective health parameters and revealing every disorder in organs and systems
      functioning.

PMID- 17217222
TI  - [Complex analysis of mutagenic and carcinogenic jeopardy of work conditions on
      JSC "Cox" in Kemerovo].
AB  - The authors present results of complex study concerning mutagenic and
      carcinogenic effects of work conditions in chemical-recovery industry. Oncologic
      morbidity and frequency of chromosomal aberrations in workers group is
      considerably higher than in controls. These effects appear to increase in males
      with longer length of service.

PMID- 17217223
TI  - [Classification of health state in workers subjected to chemical factor].

PMID- 17217224
TI  - [Evaluating diagnostic information in biologic tests of occupational medicine].
AB  - The article deals with analysis of diagnostic workup in patients having
      occupational disease diagnosed in clinical and diagnostic laboratory. All
      biochemical tests set for these patients appeared to have small diagnostic
      selectivity. Maximal diagnostic sensitivity for frequently applied tests equalled
      50%, for infrequently applied ones--80-100%.

PMID- 17217225
TI  - [Phenomenon of endogenic auto-rosetting in blood, its role in toxic anemia
      pathogenesis].
AB  - Endogenic auto-rosetting in peripheral blood was studied in workers exposed to
      paint-and-lacquer materials. Findings are increased numbers of general auto
      rosettes and of auto-rosettes with extracellular RBC lysis (p < 0.001). That was
      associated with decrease of RBC and hemoglobin (p < 0.01).

PMID- 17217226
TI  - [Characteristics of work conditions of dentists in therapeutic dentistry
      offices].

PMID- 17217227
TI  - The 2nd annual EBRI/Commonwealth Fund Consumerism in Health Care Survey, 2006:
      early experience with high-deductible and consumer-driven health plans.

PMID- 17217228
TI  - [Vascular factors and the psychopathological picture in Alzheimer's disease].
AB  - AIM: The aim of the study was to assess the impact of the vascular component on
      the psychopathological picture in Alzheimer's disease. METHOD: The study included
      50 patients with dementia of Alzheimer's type diagnosed according to the DSM-IV
      criteria. The following criteria were fulfilled: the patient's consent to
      examination, the possibility of obtaining an objective interview from a caregiver
      who knew the patient's history well. The patients were assessed with the
      following scales: the Alzheimer Disease Assessment Scale--cognitive subscale
      (ADAS-cog) and non-cognitive subscale (ADAS-non-cog), the Montgomery-Asberg
      Depression Scale (MADRS), the Instrumental Activity of Daily Living (IADL);
      moreover, there were examinations carried out with the AMDP Scale and the
      Hachinsky Scale, whose results constituted the basis for dividing the patients
      into two groups: those with a slight vascular component (the score of 0-1 on the
      Hachinsky Scale) and a prominent vascular component (the score of 2-4). RESULTS:
      Significant statistical differences between patients with slight and prominent
      vascular components were noticed; the differences referred to: somatic symptoms
      and orientation, thinking disorders, emotional disorders and "other" symptoms.
      CONCLUSION: Summing up, it must be said that the presence of vascular factors
      affects the clinical picture of Alzheimer's disease. The study shows that
      vascular factors do not intensify the severity of the very dementia itself but
      contribute to the presence of non-cognitive symptoms.

PMID- 17217229
TI  - [Assessment of behavioural and psychotic symptoms and functional status of
      nursing home residents with a diagnosis of dementia].
AB  - AIM: This study sought to determine the relationship between behavioural and
      psychopathological disturbance and the functional status of dementia patients.
      METHOD: The link between results of the Neuropsychiatric Inventory-Nursing Home
      Version (NPI-NH) and Multidimensional Observation Scale for Elderly Subjects
      (MOSES) with cognitive impairment in 23 demented and 30 non-impaired nursing home
      residents was examined. Diagnosis of dementia was based on ICD-10 criteria.
      RESULTS: Results showed that behavioural and psychotic symptoms were most often
      found in cognitively impaired residents. Several symptoms of behavioural
      pathology showed associations with lower cognitive status, including delusions,
      apathy and aberrant motor behaviour. But dementia was not associated with more
      aggressive behaviours. CONCLUSION: Results of NPI-NH were correlated
      significantly with the MOSES scale in both groups. The results suggest that some
      non-cognitive symptoms may be related to the cognitive dysfunction in dementia
      and behavioural pathology may also have impact on the patient's ability to
      function.

PMID- 17217230
TI  - [Prevalence of potentially reversible cognitive function disorders in patients of
      a memory dysfunction clinic].
AB  - Potentially reversible dementias are rarely detected in out-patient care
      facilities. Actual reversibility is virtually not known and has been occasionally
      reported in literature. AIM: To determine the prevalence of potentially
      reversible dementias among patients seen at the ambulatory care facility and to
      estimate their "real life" reversibility. METHOD: A retrospective analysis of
      medical records of 258 outpatients attending the Memory Clinic of the Central
      University Hospital of Lodz in the years 2002-2003. RESULTS: Potentially
      reversible dementia was diagnosed in 18 (5 women, mean age 60.9 +/- 4.9) subjects
      yielding 7% of all the subjects presented. These patients were significantly
      younger and the severity of their cognitive deficits milder as compared to the
      "non-reversible" cases. Treatment was successful only in 3 cases what translates
      into only 1.5% of those diagnosed as demented. Twenty seven cases with cognitive
      deficit but no dementia (depression or drugs side-effects) were claimed as
      potentially reversible and treated, in most cases (22 out of 27), successfully.
      However, within the 2 years period of follow-up in 13 of the 22 cases, the
      development of dementia was observed. CONCLUSIONS: Potentially reversible
      dementia is a rare phenomenon in ambulatory care facility. The majority of
      potentially reversible cases can be found among younger and less impaired
      patients. Even in cases treated successfully, the risk of developing dementia
      within 2 years is very high.

PMID- 17217231
TI  - [Quality of the psychiatric care in social welfare houses].
AB  - AIM: The aim of the research is a diagnosis of the level of the psychiatric help
      in social welfare houses. METHOD: The research was conducted in the form of a
      questionnaire. The questionnaire was sent at random to 60 houses of social
      welfare for people with psychic disorders on the whole territory of Poland. 37
      responses were received. RESULTS: All the houses in question provide their
      inhabitants with regular contact with a psychiatrist, 86% inside the social
      welfare house. 92% of inhabitants have no problems with obtaining referral to
      psychiatric hospital, however, 70% inhabitants of the social welfare houses have
      problems with being admitted to hospital. Half of the houses in question use
      direct compulsion. All the places studied possess therapeutic-caring teams, in
      97% of the houses treatment is based on the individual plan. 14% of the houses do
      not allow the patients to have access to the medical documentation concerning
      them. In every house integrated pharmacotherapy is used together with various
      forms of therapy, 76% of the houses involve the family of the patient into the
      therapeutic process. 78% of those studied note the existence of different factors
      reducing the quality of the psychiatric care offered. CONCLUSIONS: The level of
      psychiatric care in the social welfare houses is adjusted to the health needs of
      the patients in the majority of the houses studied. However, the inhabitants have
      to face the difficulties connected with being admitted to psychiatric hospitals
      and can have problems with gaining access to medical documentation concerning
      them. Treatment and rehabilitation of psychic disorders is based on
      individualized and multi-directional therapeutic interaction. Preparation of the
      staff providing psychiatric care, especially therapeutic-caring ones, is
      diversified in individual houses (half of the therapeutic teams do not have a
      psychiatrist, whose presence seems to be indispensable). The most essential
      factors reducing the quality of psychiatric care include insufficient financial
      resources and shortage of staff.

PMID- 17217232
TI  - [Schizophrenic disorders--does cognitive dysfunction relate to characteristics of
      course and psychopathology of the illness?].
AB  - AIM: Because of their importance both for pathogenesis or clinical aspects of the
      disease and for patients' social functioning, cognitive dysfunctions are nowadays
      often considered as basic characteristics of schizophrenic disorders. This study
      was aimed at evaluation of the correlation between some indices of disordered
      cognitive functioning on the one hand and some variables describing course and
      psychopathology of schizophrenic disorders on the other. METHOD: The study group
      consisted of 69 inpatients suffering from schizophrenia diagnosed according to
      both DSM-IV and ICD-10 criteria. Their mental state was rated by two clinical
      tools (scales: PANSS, KOSS). Also social functioning of patients in the year
      preceding current hospitalisation was rated by two scales (GAF, scale W).
      Cognitive dysfunctions were assessed by computer-aided tests from Dr. Schufried's
      Vienna Test System including measures of reaction time (RT), visual line pursuit
      (LVT), perseveration (PERSEV), and span of visual-spatial short term memory
      (CORSI). In statistical analysis simple nonparametric tests and rank correlation
      measures were applied. RESULTS: Correlations were confirmed between cognitive
      dysfunctions and social functioning prior to hospitalisation, age, duration of
      illness and number of previous hospitalizations. Dysfunctions were less severe in
      first episode patients than in patients during relapses or the residuum stage of
      illness. Overall assessments of severity of illness do not correlate with
      cognitive dysfunctions, but detailed analysis of psychopathology revealed
      correlations of the latter with such psychopathological dimensions as deficit,
      disorganization and dysphoria. Reality distortion (positive) psychopathological
      dimension did not have any correlation with cognitive measures. All indices of
      cognitive dysfunction correlated with poorer outcome of treatment of the current
      episode. All correlations confirmed were only of weak or moderate level.
      CONCLUSIONS: Cognitive dysfunctions correlate rather with unfavourable
      characteristics of the course of the illness. Results of psychopathological
      assessment hardly correlate with neuropsychological measures--cognitive
      dysfunctions are related rather to deficit (negative), disorganisation or
      dysphoria dimensions of a schizophrenic syndrome than to productive (reality
      distortion, positive) dimension of the syndrome.

PMID- 17217233
TI  - [Religiousness of patients with diagnosis of schizophrenia. Wide-ranging
      studies].
AB  - AIMS: (1) The correlations between: (1.1) various aspects of religiousness and
      (1.2) age, anxiety-state, anxiety-trait, locus of control, and, in the group of
      patients with shizophrenia: span of treatment, rate of therapy, ego
      psychopathology, paranoid and depression dimensions, self-rating of state of self
      feeling, state of feeling of illness, and quality of life and (2) the comparison
      of various aspects of religiousness of patients with schizophrenia and healthy
      people were studied. METHODS: The Scale of Christian Religiousness, Individual
      Religiousness Scale, Intrinsic, Extrinsic and Quest Religious Orientation Scales,
      Scale of Fundamentalism, State-Trait Anxiety Inventory, Rotter's questionnaire of
      locus of control, Scharfetter's questionnaire of ego psychopathology, Paranoid
      Depresivity Scale-abridgment, Frankfurt Self-feeling Scale-abridgment, visual
      analogy of self-feeling, visual analogy of feeling of illness, and questionnaire
      of quality of life (WHOQOL-BREF) were used in the study. 91 adults both of sexes,
      60 patients with a diagnosis of schizophrenia according to ICD-10 and DCR-10 in
      the diagnostic group and 31 healthy persons were studied. RESULTS: It was noticed
      that: (1) various correlations are manifested between religiousness and
      psychopathology of patients with schizophrenia; (2) patients diagnosed as having
      schizophrenia have a significantly higher level of extrinsic religiousness and
      fundamentalism than healthy individuals; (3) many results pointed out in the
      bibliography had no verification in these studies. CONCLUSIONS: Intrinsic,
      extrinsic, quest, and orthodox religiousness and fundamentalism realize
      significant functions in psychopathology of schizophrenia disorder. The knowledge
      about religiousness of schizophrenia patients can be important for diagnostic and
      therapeutic processes of the disorder.

PMID- 17217234
TI  - [Links between burden of care in parents of patients with schizophrenia or
      personality disorders and family interactions].
AB  - AIM: The aim of this study is to explore relationships between burden of care in
      parents of patients with schizophrenia or personality disorders and family
      interactions. Two main types of family interactions were distinguished according
      to Stierlin's theory: binding and expelling. Whereas binding leads to an increase
      in mutual dependency, expelling leads to a rise of mutual independence. METHOD:
      Families were divided into three groups according to the ICD-10 diagnosis of the
      index offspring (18-35 years old): (1) schizophrenia (N=33), (2) personality
      disorder (N=35), (3) control group (N=35). There were no significant differences
      in the mean age of adult children and mean age of parents, occupational patterns
      of parents, number of children in families and length of marriage between three
      groups. Subjects (mother, father and young adult) completed the originally
      designed questionnaires in which psychometric properties had been analyzed in
      earlier pilot research. RESULTS: In families with schizophrenic young adults, the
      levels of burden were elevated. However there was no statistical significance
      between the mean scores of parental burden in the families of schizophrenic
      patients and young adults with diagnosis of personality disorders. Parental
      burden was positively correlated with parents' expelling in families with young
      adults with schizophrenia or personality disorders. Father's burden was
      positively correlated with mother's expelling in all groups of families.
      CONCLUSIONS: This study suggests that the degree of parental burden may have an
      impact on family interactions.

PMID- 17217235
TI  - [Association of functional genes polymorphisms of key enzymes in the metabolism
      of biogenic amines with paranoid schizophrenia susceptibility and the influence
      of these polymorphisms on PANSS results in antipsychotic treatment].
AB  - AIM: The genetic components of the schizophrenia susceptibility are calculated as
      being 50%. We evaluated the frequency of alleles and genotypes of COMT and MAO-A
      genes polymorphisms in patients with schizophrenia and in the healthy population.
      We searched for the associations between genotypes and PANSS results among
      patients in a three month antipsychotic therapy. METHOD: The study comprised 72
      unrelated patients who met ICD-10 criteria for schizophrenia, and 187 unrelated
      healthy controls. The analysis of COMT and MAO-A genes polymorphisms were
      performed using the polymerase chain reaction technique (RFLP-restriction
      fragments length polymorphism and VNTR-variable number tandem repeats). The
      severity of psychopathological symptoms was measured by the PANSS (Positive and
      Negative Schizophrenia Scale). RESULTS: We did not find an association between
      the genotype of COMT and MAO-A genes polymorphisms and schizophrenia. We found
      statistically significant different allele distribution in MAO gene polymorphism:
      alleles with three tandem repeats in the promoter region were more frequent among
      females with schizophrenia. We did not find any association between the genotype
      of COMT and MAO-A genes polymorphisms and PANSS results in any time periods. Due
      to a small number of patients in this study the obtained results should be
      regarded as preliminary.

PMID- 17217236
TI  - [Lack of association between the insertion/deletion polymorphism in the serotonin
      transporter gene and schizophrenia].
AB  - AIM: The authors analyzed the association between polymorphism of serotonin
      transporter gene and schizophrenia. This polymorphism is characterised by a 44-bp
      insertion or deletion in the promoter region of the gene which influences its
      transcriptional activity. METHOD: 349 not related patients with paranoid
      schizophrenia were included in this study. Using the SCID (Structured Clinical
      Interview for DSM-IV Axis I Disorders) a consensus diagnosis, according to the
      DSM-IV criteria was made by two independent psychiatrists for each patient. The
      control group consisted of 372 persons who have not been examined by
      psychiatrists. Genomic DNA was extracted from whole blood leukocytes using a
      salting out method. The polymorphism was amplified by the polymerase chain
      reaction (PCR). We received two products of PCR: 406 base pairs (short allele)
      and 450 base pairs (long allele). RESULTS: We analyzed genotypes and alleles of
      the 5-HTTLPR polymorphism in the group of patients and in the control group. We
      also divided our sample according to their gender and early onset of
      schizophrenia. The analysis did not show any significant differences between the
      studied groups. CONCLUSIONS: In the present study no association between 5-HTTLPR
      polymorphism and schizophrenia was found.

PMID- 17217237
TI  - [Manganese superoxide dismutase gene (MnSOD) polimorphism in schizophrenics with
      tardive dyskinesia from central Poland].
AB  - Tardive dyskinesias (TD) are serious side effect symptoms appearing in the course
      of many years' neuroleptic treatment. On average, TD appear in 20% patients who
      take neuroleptics chronically. The free radical hypothesis of tardive dyskinesias
      assumes that they come into existence due to cholinergic neuron damage in the
      extra-pyramidal system by reactive oxygen species (ROS). Manganese superoxide
      dismutase (MnSOD) plays a key role in protection against ROS. AIM: The aim of
      this study was to evaluate functional gene polymorphism for MnSOD in
      schizophrenic patients with tardive dyskinesias presence. METHOD: 122 paranoid
      schizophrenia patients were invited to paticipate in the study. TD symptoms were
      observed in 57 people. The evaluation was performed by applying the PANSS scale,
      while TD increase was evaluated with the AIMS scale. RESULT: Statistical
      association in allele incidence frequency (p < 0.001) and in a genotype layout
      was observed between the control group and the schizophrenic group (p < 0.001),
      and also in a genotype layout between the TD group and the control group (p <
      0.001). Allele layout also differentiated the control group and the TD symptoms
      group (p < 0.05). Relative risk for developing schizophrenia and TD development
      depends on the genotype in the gene for MnSOD. CONCLUSION: In the Polish
      population there is a statistically substantial association between schizophrenia
      incidence and the Val-9Val genotype in a gene for MnSOD. Schizophrenic patients
      having a Val-9Val genotype in the gene for MnSOD have nearly a ten times higher
      risk for developing TD than schizophrenics not having this genotype. Risk for
      developing schizophrenia for people having the Val-9Val genotype in the gene for
      MnSOD is over three times higher than for people lacking this genotype.

PMID- 17217238
TI  - [May the dialogue between genes and environmental factors modify the behavioural
      phenotype of Rett syndrome and others?].
AB  - Formation of a phenotype during development of the human being may result from a
      specific dialogue between genes and environmental factors. Expression of
      particular genes is controlled not only on the transcriptional level but also on
      the level of accessibility of genetic information through the influence for
      remodelling of chromatin. We characterized Rett syndrome and its molecular basis
      as an example of the relation between genes and environment and their influence
      on epigenetic processes determining the gene expression. Examples of importance
      of DNA methylation in psychiatric disorders were shown.

PMID- 17217239
TI  - [Imaging of hypnosis with functional magnetic resonance].
AB  - AIM: The aim of the study was imaging of the central nervous system activity with
      the fMRI method during hypnosis as well as confirmation of the observations
      linking subjective effects of suggested analgesia with the functional changes on
      the neurophysiological level. METHOD: At first volunteers (7 female, 7 male) were
      examined with fMRI in the resting state and then four times during application of
      painful stimuli such as pricking of the right hand. Four experimental conditions
      were associated with this stimulation: only nociceptive stimulation, after
      analgesic suggestion, after hypnotic induction and after consecutive analgesic
      suggestion in hypnosis. In the fifth condition, concentration of attention was an
      experimental condition, while the control condition was distraction of attention
      (e.g. free associations). The contrast differences between measurements in the
      consecutive phases of the experiment were analysed. RESULTS: Decreases of
      activity of regions known for contributing to pain reception were found, probably
      as an effect of analgesic suggestion. This effect was seen especially in the area
      of L-thalamus. Suggestion (more precisely--the reception of its content) was
      related mainly to the R-ACG area activity growth. Hypnotic induction was
      correlated with increasing activity of the L-orbitofrontal gyrus. Concentration
      of attention was linked with activity increase within inferior parietal lobule,
      occipital middle/superior gyri; in the left hemisphere in the orbital frontal
      gyri and insula/frontal operculum. CONCLUSION: Both hypnosis and reception of
      analgesic suggestion are linked with increasing activity in particular brain
      areas, whereas the effect of analgesic suggestion demonstrates itself in the fMRI
      mainly by diminishing the reaction on painful stimuli.

PMID- 17217240
TI  - [Influence of impulsivity, suicidality and serotonin genes on treatment outcomes
      in alcohol dependence].
AB  - AIM: The aim of the study was to identify risk factors of relapse by
      investigating relationships among suicidality, impulsivity, genetic markers of
      serotonin activity, and relapse in alcohol-dependent patients. METHODS: 90
      alcohol dependent patients were followed for 12 months after the baseline
      assessment, which entailed evaluation of suicidality and impulsivity as well as
      collection of DNA samples. Polymorphisms of genes involved in the synthesis and
      activity of the serotonin system were analyzed. After 12 months from the first
      visit, the patients were re-contacted and interviewed for relapse. RESULTS:
      Relapse rates were significantly higher among patients with the history of
      suicidal attempts recorded at the baseline assessment. The genetic analysis
      showed that patients with the G/G genotype in the 5HTR1A gene were more likely to
      relapse, whereas patients with the C/C genotype were more likely to abstain.
      Moreover, there was a strong trend for an association between the G/G genotype
      and a history of suicide attempts. CONCLUSIONS: High level of suicidality may
      predict relapse in alcoholic patients. Altered serotonergic function increases
      the risk of a suicide attempt and may contribute to higher risk of relapse in
      alcohol dependent patients.

PMID- 17217241
TI  - [Atypical antipsychotic-induced weight gain].
AB  - Introduction of a new group of antipsychotic drugs, called atypical because of
      the proprieties differing them from classical neuroleptics, gave hope for the
      beginning of a new era in treatment of psychoses, including schizophrenia.
      Different mechanisms of action not only resulted in a broader spectrum of action
      and high efficacy but also in a relative lack of extrapiramidal symptoms.
      However, atypical neuroleptics are not totally free from adverse effects.
      Symptoms such as sedation, metabolic changes and weight gain, often very quick
      and severe - present also in the case of classical drugs, but put to the
      background by extrapiramidal symptoms--have become prominent. Weight gain is
      important both from the clinical and subjective point of view--as associated with
      serious somatic consequences and as a source of enormous mental distress. These
      problems are addressed in this review, with the focus on weight gain associated
      with the use of specific atypical neuroleptics.

PMID- 17217242
TI  - [Antipsychotic-induced weight gain--pharmacogenetic studies].
AB  - Drug-naive patients with schizophrenia often present metabolic abnormalities and
      obesity. Weight gain may be the side effect of treatment with many antipsychotic
      drugs. Genetic effects, besides many other factors, are known to influence
      obesity in patients with schizophrenia treated with antipsychotics. Numerous
      studies of several genes' polymorphisms have been performed. -759C/T polymorphism
      of 5HT2C gene attracted most attention. In 5 independent studies of this
      polymorphism the association between T allele with the lower AP-induced weight
      gain was detected. No associations could be detected between weight gain and
      other polymorphisms of serotonergic system genes as well as histaminergic system
      genes. Studies of adrenergic and dopaminergic system have neither produced any
      unambiguous results. Analysis of the newest candidate genes (SAP-25, leptin gene)
      confirmed the role of genetic factors in AP-induced weight gain. It is worth
      emphasising, that the studies have been conducted in relatively small and
      heterogenic groups and that various treatment strategies were used.

PMID- 17217243
TI  - [Characteristics of the brain system activity and vegetative function formation
      in children under conditions of the European north (a problem study)].
AB  - Results of complex medical-physiological research performed during 10 scientific
      expeditions in Arkhangelsk region in 2003-2005 are presented. Influence of
      climatic-geographic, biogeochemical and social conditions of North-West region of
      Russia on sexual maturation, formation of the brain structural-functional
      organization, vegetative functions, immunological and biochemical status of
      schoolchildren was studied with the aid of modern neurophysiologic (computer
      electroencephalography, computer rheoencephalography, computed electric dipole
      origin tomography, etc.), psychophysiological and psychometric methods
      (evaluation of cognitive and mnestic functions, Vechsler 1Q estimation),
      biochemical assessment of monoamine oxidase and butyrylcholinesterase activity,
      physical-chemical analysis of macro- and microelements in the organism.

PMID- 17217244
TI  - [Reflection of cortical activation pattern in the human EEG phase structure].
AB  - Investigation was fulfilled on healthy subjects (22) and on outpatients (62). The
      EEG by the standard scheme as recorded at resting with open and closed eyes and
      under different functional loads. These records were processed in accordance with
      the EEC phase structure with the aid of computer animation technology. The main
      idea of the phase structure technology consists in rejection of one supporting
      lead. Time shifts were measured only between two neighbouring electrodes, so that
      the oscillations under comparison were always highly coherent. Time errors were
      evaluated according to crosscorrelation function maximum shift. The differences
      between high- and low-frequency EEG rhythms were shown to be only quantitative
      from the phase structure viewpoint. Qualitatively, the rhythm properties were
      equal and came to slow (second) phase structure oscillations. Low frequency
      activity compared to high frequency one was characterized by greater phase shifts
      from electrode to electrode. Phase shifts of potentials are forming the structure
      which, as a whole, is very similar in different people and is reproduced in
      different states. Initial EEG waves appearance is statistical linked with main
      sensory projections: visual (occiput), auditory (temples) and somatic (parietal
      region) with addition of frontal region. Redistribution of phase leadership in
      favor of occipital pole and to both temporal regions when eyes are open is
      described. It is apparently dependent on the sensory surge level from thalamus to
      a given cortex region. Phase gradient direction seems to reflect the cortex
      current density gradient which is parallel to surface. It can be used for
      localization of compact sources lying near to cortex.

PMID- 17217245
TI  - [Intranasal epitalon infusion modulates neuronal activity in the rat neocortex].
AB  - Properties of tetrapeptide epitalon (Ala-Glu-Asp-Gly) constructed on the basis of
      pineal peptide extract, have been studied. The intranasal infusions: a
      noninvasive way to deliver this peptide to CNS hypassing the blood-brain barrier,
      was used. The aim of the study is to estimate epitalon action on rat motor cortex
      spontaneous activity. Wistar male rats were anesthetized with urethane (1 g/kg).
      Extracellular unit recording was made using glass microelectrodes (1-2 MOhm).
      After recording of spontaneous activity (10-15 min), epitalon intranasal infusion
      (2 ng) was followed by 30-minute recording. Within a few minutes after the
      infusion, significant activation of neural activity was observed (2-2.5-fold
      higher frequency of neuronal spikes). Complex response consisting of several
      phases was identified in some recordings. The spikes frequency growth during 5 to
      7 min (first phase) after the infusion was followed by the second (11-12 min) and
      the third (17-18 min) phases. An increase of neuronal spontaneous activity was
      conditioned by the higher frequency of already active units and by the
      involvement of previously silent cells. At least the first phase of epitalon
      action can be explained by direct action of the peptide on the cells of the motor
      cortex.

PMID- 17217246
TI  - [NO-dependent mechanisms of the amygdalofugal modulation of the hypothalamus
      vegetative neurons].
AB  - In neurophysiological and histochemical experiments on rats, amygdalo-fugal
      modulation of cells within NO-producing areas of the hypothalamus was studied.
      Electrical stimulation of the medial area of the central nucleus caused obvious
      excitatory neuronal reactions within the medial part of the paraventricular
      nucleus and rostral portion of the lateral hypothalamic area. The observed
      amygdala-induced neuronal responses were enhanced after i.v. N-nitro-1-arginine
      methyl ester (L-NAME, 10 mg/kg). The nistochemical study revealed that the
      central nucleus stimulation caused an increase in number and optical density of
      the NADPH-d-positive cells within the parvicellular zone of the paraventricular
      nucleus and in the medial part of the lateral hypothalamic area. The NO-producing
      cells within the ventrolateral part of the lateral hypothalamic area were
      inhibited. The described phenomenon may underlie the amygdalo-fugae modulation of
      autonomic outflow.

PMID- 17217247
TI  - [The phenomenon of lowering a seizure readiness level after frequent audiogenic
      seizures in Krushinskii-Molodkina rats].
AB  - The spectral analysis of the EEG activity of several brain structures
      (somatosensory, visual and auditory areas of the cortex, hippocampus, caudate
      nucleus and central medial thalamic nucleus) in the wakefulness-sleep cycle in
      Krushinskii--Molodkina strain rats with inherited predisposition to audiogenic
      seizures using long-lastint reducing of the seizure readiness level revealed in
      these animals after frequentative audiogenic generalized tonicclonic seizures,
      was performed. The reducing susceptibility to convulsiogenic sound stimuli in
      rats correlated with a decrease of the theta-range' waves level and increase of
      the expression alpha-range waves in the EEG during wakefulness. Probable role of
      reorganized functions of ascending activating brain systems in origination of the
      long reduction of susceptibility to the sound after frequentative audiogenic
      convulsions in rats is discussed.

PMID- 17217248
TI  - [The brain is one of the most important sources of dopamine in general
      circulation during perinatal ontogenesis in rats].
AB  - This study was aimed to test our hypothesis that dopamine synthesized in the
      neurons of the brain is delivered to the general circulation in rats during
      prenatal and early postnatal periods, i.e. before the establishment of the blood
      brain barrier. Using the high performance liquid chromatography, it was
      demonstrated that the dopamine concentration and content in the peripheral blood
      in fetuses and neonatal rats (i.e. before the establishment of the blood-brain
      barrier) greatly exceeded those in adult rats. Moreover, the establishment of the
      blood-brain barrier was accompanied by the significant increase of the dopamine
      concentration in the brain. A drop of the dopamine concentration in fetal plasma
      after the microsurgical lesion of the forebrain and mesencephalon
      (encephalectomy) are considered as direct evidence in favour of our hypothesis.

PMID- 17217249
TI  - [Aggression and composition of conflicting pairs in Green monkeys].
AB  - The aggressive behaviour of Green monkeys (Chlorocebus aethiops) maintained in
      corrals of Adler Primate Center was studied. The influence of the composition
      conflicting pairs, the quality of their relationships as well as the relatedness
      and hierarchic relations between the antagonists on the intensity and structure
      of aggressive relationships was investigated. It was found that the frequency of
      contact forms of aggression was not dependent on the composition of conflicting
      pairs of animals. At the same time, the frequency of non-contact forms of
      aggression was influenced by such parameters as the membership of antagonists in
      the same or different gender categories, belonging to one or different
      matrilines, as well as the quality of relationships and the rank of antagonists.

PMID- 17217250
TI  - [The sino-atrial node as an indicator of oscillatory processes in the
      cardiovascular system].
AB  - The spectrogram of heart rate in denervated (vagotomy + propranolol) and
      artificially ventilated cats always contains the true respiratory peak and 1-3
      resonance ones pacing at intervals equivalent to frequency of breathing.
      Hypothermic decrease of heart rate periodically draws the splitting of
      respiratory peaks and generation of supplementary rate-dependent peaks reflecting
      the interference of heart and breathing rhythms. The functional base for
      detection of mentioned peaks is myogenic reaction of sino-atrial node to its
      extension by fluctuations of venous inflow.

PMID- 17217251
TI  - [Cardiorespiratory responses of animals to passive orthostasis after intermittent
      hypoxia during head-down tilt].
AB  - Cardiorespiratory responses induced by upright tilt before and after intermittent
      hypoxia during head-down tilt, were investigated in rabbits. Arterial blood
      pressure, heart rate, central venous pressure, transmural filling pressure of the
      heart (calculated as the product of esophageal and central venous pressure),
      breathing frequency, esophageal pressure were measured in supine (baseline), head
      down and upright posture. Our results indicate a reduction in orthostatic
      responses in cardiovascular system after intermittent hypoxia.

PMID- 17217252
TI  - [Compensatory gastroprotective action of glucocorticoid hormones in the rats with
      ablation of capsaicin-sensitive neurons].
AB  - We tested the hypothesis that contribution of glucocorticoids in gastroprotection
      become especially important during ablation of capsaicin-sensitive neurons. For
      this, the effect of desensitization of capsaicin-sensitive neurons on the gastric
      mucosa was compared in groups of rats with different glucocorticoid supply: sham
      operated and adrenalectomized without and with corticosterone replacement (4
      mg/kg sc). Functional ablation of capsaicin-sensitive neurons was performed with
      neurotoxic doses of capsaicin (20 + 30 + 50 mg/kg sc). Indomethacin in the dose
      35 mg/kg was given as an ulcerogenic stimulus. It was shown that combination of
      adrenalectomy with desensitization of capsaicin-sensitive neurons potentiated the
      effect of sensory desensitization alone on indomethacin-induced gastric erosions.
      Corticosterone replacement prevented this effect of adrenalectomy. The results
      suggest a pivotal compensatory role of glucocorticoids in maintenance of gastric
      mucosal integrity during ablation of caspsaicin-sensitive sensory neurons.

PMID- 17217253
TI  - [Psychomotor responsiveness to corticoliberin in rats with active and passive
      adaptive strategy in water-immersion paradigm of depression].
AB  - A single intranasal injection of CRH alters adaptive behavior only in active
      rats. In particular this procedure results in increase of their behavioral
      passivity and reduction of psychomotor responsiveness. This neurohormone causes
      the same effect in active rats being injected by means of the same routine 20
      days after animals have been exposed to a single water-immersion stress. But this
      effect of CHR is not observed after injection of the neurohormone to depressed
      animals in the stress-restress paradigm. Passive rats, intact or depressed, do
      not show any behavioral changes, while active ones develop signs of depression
      after repeated CRH intranasal injection.

PMID- 17217254
TI  - [The presence of nitric oxide synthase in mucosal epithelial cells of the frog
      urinary bladder].
AB  - In experiments on frog Rana temporaria L. urinary bladder, we investigated
      localization of NO-synthase (NOS) in urinary bladder slices and measured NOS
      activity in the suspension of mucosal epithelial cells. Intensive NADPH
      diaphorase staining which is widely used as an indicator of NOS activity was
      found in mucosal epithelium. Almost all mucosal epithelial cells isolated in Ca2+
      -free conditions demonstrated positive NADPH-diaphorase reactivity. Direct
      measurement of NOS activity in suspension of mucosal cells determined by the rate
      of conversion of L-arginine to L-citrullin showed that the enzyme activity was
      reduced in absence of external Ca2+ and was inhibited by L-NAME: non-specific NOS
      inhibitor, and 1400 W: a highly selective iNOS inhibitor (control: 754 +/- 184; L
      NAME, 1 mM 329 +/- 87; 1400 W, 20 mM: 547 +/- 25; Ca2+ -free/EDTA: 490 +/- 184
      cpm [3H]-citrullin/10(6) cells per 45 min, p < 0.05, n = 7-8). The data obtained
      demonstrate that frog urinary bladder mucosa epithelial cells provided
      antidiuretic hormone-induced increase of osmotic water permeability contain
      nitric oxide synthase. The presence of inducible (iNOS) as well as constitutive
      isoform(s) revealed in these cells allows to suggest involvement of NOS in
      intracellular signaling pathways regulated water transport across the epithelium.

PMID- 17217257
TI  - 1,3,5-triazine-based mass spectral tagging of one-bead one-compound libraries.
AB  - A triazine-based mass encoding strategy that accommodates cleavable linker,
      isotopic labeling, and diversity receptor moieties is reported. The resulting
      triazine-based tags, which are coupled to bifunctionalized TentaGel resin in a
      one-pot transformation, enable the construction of a 1-oxa-2,8-diazaspiro[4.5]dec
      2-ene-7-carboxamide library and facilitate decoding by equalizing the ionization
      potential of the liberated tags in single bead MALDI-TOF experiments as well as
      balancing the reactivity of the starting tags in the resin coupling step.
      [reaction: see text].

PMID- 17217256
TI  - Cancer/testis (CT) antigens are expressed in fetal ovary.
AB  - Cancer/testis (CT) antigens are named after their expression pattern as they are
      typically present in various types of tumors and in the germ cells of normal
      adult testis. Adult ovarian tissue is usually reported to be CT antigen negative.
      Based on the differences in female versus male gonadal development, the ovarian
      counterpart of the most predominant CT antigen positive testicular germ cells are
      not prevalent in the adult ovary. Hence, we analyzed the protein expression of
      several CT antigens in fetal ovary by immunohistochemistry with various
      monoclonal antibodies (mAbs) previously generated by our group. The mAbs used
      were: MA454 (MAGE-A1), M3H67 (MAGE-A3), 57B (MAGE-A4), CT7-33 (CT7/MAGE-C1), and
      ES121 (NY-ESO-1). All mAbs showed some immunopositivity in fetal ovarian germ
      cells. The most intense staining was seen with mAbs M3H67, 57B, and CT7-33 during
      weeks 16-23 of gestation. The most prevalent cells stained were oogonia, with
      only focal staining of oocytes of the primordial follicle. We conclude that CT
      antigens are regularly expressed in fetal ovarian germ cells and might play an
      important role in male and female germ cell biology.

PMID- 17217259
TI  - Efficient one-pot synthesis of fluorinated benzimidazolines, benzothiazolines,
      benzoxazolines, and dihydrobenzoxazinones using gallium(III) triflate as a
      catalyst.
AB  - One-pot synthesis of fluorinated benzimidazolines, benzothiazolines,
      benzoxazolines, and dihydrobenzoxazinones was easily achieved under mild
      conditions in high yields and purity through gallium(III) triflate mediated
      condensation-cyclization. Introduction of fluorine atoms favors the formation of
      the five-membered heterocycles over seven-membered heterocycles. [reaction: see
      text].

PMID- 17217258
TI  - Silica-supported sodium sulfonate with ionic liquid: a neutral catalyst system
      for Michael reactions of indoles in water.
AB  - A neutral catalytic system for Michael reactions of indoles has been developed by
      combining silica-supported benzenesulfonic acid sodium salt with hydrophobic
      ionic liquid in water. An efficient hydrophobic environment could be created on
      the surface of the silica-sodium material under the conditions. Various indole
      derivatives and alpha,beta-unsaturated carbonyl compounds including some acid
      labile substrates were successfully applied to this system with water as the sole
      solvent to afford the desired Michael adducts in high yields. [structure: see
      text].

PMID- 17217260
TI  - Efficient synthesis of phenanthridinone derivatives via a palladium-catalyzed
      coupling process.
AB  - A palladium-mediated domino reaction was developed to conveniently synthesize
      phenanthridinone derivatives. Phosphine ligand 1 strongly promotes the domino
      process, which includes aryl-aryl coupling and C-N bond formations concomitant
      with a deamidation reaction. The versatility and applicability to a broad range
      of substrates make this reaction useful for the development of bioactive
      derivatives. [reaction: see text].

PMID- 17217261
TI  - Asymmetric synthesis of cyclopropylamines starting from N-sulfinyl alpha-chloro
      ketimines.
AB  - Treatment of novel chiral N-sulfinyl alpha-chloro ketimines with Grignard
      reagents resulted in the synthesis of chiral N-(1-substituted cyclopropyl)-tert
      butanesulfinamides in acceptable to good yields and diastereoselectivity via 1,3
      dehydrohalogenation and subsequent addition of the Grignard reagent to the
      intermediate cyclopropylideneamine. Only in the case of allylmagnesium chloride
      did the reaction lead to aziridines in high yield. Further deprotection toward N
      unprotected 1-substituted cyclopropylamines was established, and the absolute
      configuration was determined. [reaction: see text].

PMID- 17217262
TI  - Novel synthetic approach toward (+/-)-beta-cuparenone via palladium-catalyzed
      tandem Heck cyclization of 1-bromo-5-methyl-1-aryl-hexa-1,5-dien-3-ol
      derivatives.
AB  - A novel and convenient synthetic route toward (+/-)-beta-cuparenone and many
      other sesquiterpene natural product precursors has been developed via palladium
      catalyzed tandem Heck cyclization of 1-bromo-5-methyl-1-aryl-hexa-1,5-dien-3-ols.
      [reaction: see text].

PMID- 17217263
TI  - Base-assisted regio- and diastereoselective conversion of functionalized furans
      to butenolides using singlet oxygen.
AB  - A facile synthesis of beta-functionalized gamma-hydroxybutenolides was achieved
      using a Baylis-Hillman reaction followed by singlet oxygen oxidation. The
      conversion from 3-furfural was regio- and diastereoselective. [reaction: see
      text].

PMID- 17217264
TI  - Phosphatidylcholine-derived bolaamphiphiles via click chemistry.
AB  - The copper-catalyzed azide alkyne cycloaddition is employed to modify
      phosphatidylcholine precursors with sn-2 acyl chains containing terminal alkyne
      or azide groups. Although the reactions are conducted as biphasic dispersions,
      the yields are essentially quantitative. Bolaamphiphiles are formed by simply
      clicking together two phosphatidylcholine alkyne precursors to a central bisazide
      scaffold. The chemistry introduces polar 1,4-triazole units into the lipophilic
      region of the bilayer membrane, and the bolaamphiphiles do not form stable
      vesicles. [structure: see text].

PMID- 17217265
TI  - Beta-aminoethyltrifluoroborates: efficient aminoethylations via Suzuki-Miyaura
      cross-coupling.
AB  - A set of phenethylamines has been successfully prepared via Suzuki-Miyaura cross
      coupling of diverse potassium beta-aminoethyltrifluoroborates with aryl halides.
      The potassium beta-aminoethyltrifluoroborates were easily prepared via
      hydroboration of enamine and enamide precursors. [reaction: see text].

PMID- 17217266
TI  - trans-acetonide controlled endo-selective intramolecular nitrone-alkene
      cycloaddition of hept-6-enoses: a facile entry to calystegines, tropanes, and
      hydroxylated aminocycloheptanes.
AB  - High-yielding endo-selective intramolecular nitrone-alkene cycloaddition (INAC)
      reactions of hept-6-enoses controlled by a trans-acetonide to give bridged
      bicyclo[4.2.1]isoxazolidines exclusively are realized for the first time. The
      cycloadducts were readily transformed into calystegine, tropane, and hydroxylated
      aminocycloheptane frameworks. [reaction: see text].

PMID- 17217267
TI  - Lewis acid tuned facial stereodivergent HDA reactions using beta-substituted N
      vinyloxazolidinones.
AB  - The [4 + 2] acido-catalyzed heterocycloaddition between new beta-substituted N
      vinyl-1,3-oxazolidin-2-ones (with R' = Me, Ar, CH2 Ar) and beta,gamma-unsaturated
      alpha-ketoesters (R = Ar) afforded heteroadducts with high levels of endo and
      facial selectivities. A complete reversal of facial differentiation was achieved
      by varying the Lewis acid, leading to the stereoselective formation of either
      endo-alpha or endo-beta adducts. [reaction: see text].

PMID- 17217268
TI  - Highly efficient synthesis of enantiomerically enriched 2-hydroxymethylaziridines
      by enzymatic desymmetrization.
AB  - Both enantiomers of protected and unprotected 2-hydroxymethylaziridines are
      efficiently and enantiospecifically synthesized by using a combination of
      enzymatic and synthetic methods. PPL was used for lipase-catalyzed
      desymmetrization of N-protected serinol. [reaction: see text].

PMID- 17217269
TI  - New solid support for the synthesis of 3'-oligonucleotide conjugates through
      glyoxylic oxime bond formation.
AB  - A novel solid support 1 was synthesized to incorporate glyoxylic aldehyde
      functionality at the oligonucleotide 3'-terminus. 6-mer and 11-mer
      oligonucleotide sequences containing 3'-glyoxylic aldehyde functionality were
      prepared by using this support. These modified oligonucleotides were coupled to
      reporters containing an aminooxy group to prepare oligonucleotide 3'-conjugates
      through glyoxylic oxime bond formation. The hydrolytic stability of a glyoxylic
      oxime linkage was also investigated. [reaction: see text].

PMID- 17217270
TI  - Enantiopure pseudo-C3-symmetric titanium alkoxide with propeller-like chirality.
AB  - An enantiopure amine tris(phenolate) ligand containing a single stereogenic
      center has been used to control the propeller-like chirality of a derived pseudo
      C3-symmetric titanium isopropoxide complex with excellent levels of
      diastereocontrol. [structure: see text].

PMID- 17217271
TI  - Synthesis of psymberin analogues: probing a functional correlation with the
      pederin/mycalamide family of natural products.
AB  - In this letter we describe an efficient synthesis of "psympederin", a hybrid
      between the novel antitumor natural product psymberin and the blister beetle
      toxin pederin. Evaluation of antiproliferative activity reveals that the
      dihydroisocoumarin fragment is important for psymberin toxicity and the cyclic
      pederate fragment is important for pederin/mycalamide toxicity. On the basis of
      preliminary results described herein, we speculate that, despite their structural
      resemblance, psymberin and pederin/mycalamide induce toxicity through different
      mechanisms. [reaction: see text].

PMID- 17217272
TI  - Assembling a mixed phthalocyanine-porphyrin array in aqueous media through host
      guest interactions.
AB  - A stable 1:1 host-guest complex is formed between a silicon(IV) phthalocyanine
      conjugated axially with two permethylated beta-cyclodextrin units and a
      tetrasulfonated porphyrin. The complex exhibits a light-harvesting property and
      works as an efficient photosensitizing system, killing HT29 human colon
      adenocarcinoma cells with an IC50 value of 0.09 microM. [structure: see text].

PMID- 17217273
TI  - The unusual electrochemical and photophysical behavior of 2,2'-bis(1,3,4
      oxadiazol-2-yl)biphenyls, effective electron transport hosts for phosphorescent
      organic light emitting diodes.
AB  - The fluorescence and phosphorescence of 2,2'-bis(5-phenyl-1,3,4-oxadiazol-2
      yl)biphenyl shows good spectral matching with the absorption spectra of the MLCT1
      and MLCT3 transitions of Ir(ppy)3. The red-shift of the 0-0 band in the
      phosphorescence at 77 K is due to the intramolecular pi-pi interactions between
      the oxadiazole side chains. Maximum brightness of 43,000 cd/m2 with an efficiency
      of 26 cd/A at 200 cd/m2 was achieved when BOBP was used as the host material for
      Ir(ppy)3 in the PHOLED study. [structure: see text].

PMID- 17217274
TI  - Ascospiroketals A and B, unprecedented cycloethers from the marine-derived fungus
      Ascochyta salicorniae.
AB  - Chemical investigation of the marine-derived fungus Ascochyta salicorniae led to
      the isolation of two novel natural products, ascospiroketals A (1) and B (2).
      From a biosynthetic standpoint, the compounds possess new ring systems.
      [structure: see text].

PMID- 17217275
TI  - Simple but effective way to sense pyrophosphate and inorganic phosphate by
      fluorescence changes.
AB  - A new fluorescent chemosensor based on the acridine-Zn(II) derivative effectively
      recognizes pyrophosphate and inorganic phosphate at pH 7.4. Acridine derivative 1
      displayed a fluorescent quenching effect with pyrophosphate; on the other hand, a
      large fluorescent enhancement was observed with inorganic phosphate. [structure:
      see text].

PMID- 17217276
TI  - Synthesis of protected chiral vicinal diaminoalcohols by diastereoselective
      intramolecular benzylic substitution from bistrichloroacetimidates.
AB  - An efficient synthesis of chiral dihydrooxazines (2) from 1-aryl-2-amino-propane
      1,3-diols (1) via the corresponding bistrichloroacetimidate intermediates has
      been developed. In this transformation, one trichloroacetimidate acts as a
      leaving group and the other acts as a nucleophile. The cyclization proceeds
      through an SN1 mechanism to provide trans-dihydrooxazines with complete
      diastereoselectivity irrespective of the absolute configuration of the benzylic
      alcohol. The transformation of 2 into other selectively protected aminodiols is
      also documented. [reaction: see text].

PMID- 17217277
TI  - Asymmetric amplification in catalysis by trans-1,2-diaminocyclohexane
      bistriflamide.
AB  - A strong asymmetric amplification is observed in the addition of diethylzinc on
      aromatic aldehydes in the presence of the bistriflamide of trans-1,2
      diaminocyclohexane 3a. The asymmetric amplification originates from the
      insolubility of the catalyst precursor 3a of low enantiomeric excess (ee), with a
      concomitant large increase of ee for the minor soluble part of 3a. Controlled
      mono-N-acetylation of 3a (20% ee) at -78 degrees C allowed isolation of 4
      possessing 90% ee. [reaction: see text].

PMID- 17217278
TI  - Asymmetric hydrogenation of alpha-chloro aromatic ketones catalyzed by eta6
      arene/TsDPEN-ruthenium(II) complexes.
AB  - Asymmetric hydrogenation of various alpha-chloro aromatic ketones with
      Ru(OTf)(TsDPEN)(eta6-arene) (TsDPEN = N-(p-toluenesulfonyl)-1,2
      diphenylethylenediamine) produces the chiral chlorohydrins in up to 98% ee. This
      reaction can be conducted even on a 206-g scale. The hydrogenation of an alpha
      chloro ketone with a phenol moiety has been utilized for the synthesis of (R)
      norphenylephrine without protection-deprotection operations. [reaction: see
      text].

PMID- 17217279
TI  - Second generation catalytic asymmetric synthesis of Tamiflu: allylic substitution
      route.
AB  - Catalytic asymmetric synthesis of Tamiflu, an important antiinfluenza drug, was
      achieved. After the catalytic enantioselective desymmetrization of meso-aziridine
      3 with TMSN3, using a Y catalyst (1 mol %) derived from ligand 2, an allylic
      oxygen function and C1 unit on the C=C double bond were introduced through
      cyanophosphorylation of enone and allylic substitution with an oxygen
      nucleophile. This second generation route of Tamiflu is more practical than our
      previously reported route. [reaction: see text].

PMID- 17217280
TI  - Nickel-catalyzed thioallylation of alkynes with allyl phenyl sulfides.
AB  - Allylic sulfides add to alkynes in the presence of nickel complexes efficiently
      to afford thio-1,4-dienes regio- and stereoselectively. Functional groups such as
      alkoxy, siloxy, hydroxy, carboalkoxy, chloro, and cyano groups are tolerated. A
      mechanism that involves a pi-allyl nickel intermediate is proposed on the basis
      of isolation of pi-allyl complexes and distribution of products in the reactions
      of alpha- or gamma-methylated allyl sulfide. [reaction: see text].

PMID- 17217281
TI  - Directed reductive amination of beta-hydroxy-ketones: convergent assembly of the
      ritonavir/lopinavir core.
AB  - An efficient procedure for the directed reductive amination of beta-hydroxy
      ketones (3) for the stereoselective preparation of 1,3-syn-amino alcohols (6) is
      reported. The operationally simple protocol uses Ti(iOPr)4 for coordination of
      the intermediate imino alcohol (5) and PMHS as the reducing agent. The method was
      expanded to an asymmetric aldol reductive amination sequence to allow a highly
      convergent synthesis of the hydroxy-amine core of the HIV-protease inhibitors
      ritonavir and lopinavir. [reaction: see text].

PMID- 17217282
TI  - Flexible strategy for differentially 3,5-disubstituted 4-oxypyridin-2(1H)-ones
      based on site-selective Pd-catalyzed cross-coupling reactions.
AB  - 3,5-Dihalogeno-4-methoxy-N-methylpyridin-2(1H)-ones have been shown to undergo
      single Suzuki coupling reactions in a site-selective fashion. Monoarylations
      occur at the C-5 position preferentially, thus leaving the remaining C-3 halide
      free for further functionalization, to finally access differentially 3,5
      disubstituted 2-pyridones. This two-step strategy has been applied to the
      elaboration of the 3-acyl-5-aryl-4-oxy-2-pyridone subunit that is prevalent in
      numerous bioactive natural products. [reaction: see text].

PMID- 17217283
TI  - Palladium-catalyzed cross-coupling between vinyl halides and tert-butyl
      carbazate: first general synthesis of the unusual N-Boc-N-alkenylhydrazines.
AB  - N-Boc-N-alkenylhydrazines, an almost unknown type of compounds, have been
      prepared with high to moderate yields via palladium-catalyzed cross-coupling
      between alkenyl halides and tert-butyl carbazate. The present methodology
      represents the first general way to access this highly functionalized and unusual
      type of hydrazines. [reaction: see text].

PMID- 17217285
TI  - Total synthesis of flustramine C via dimethylallyl rearrangement.
AB  - The marine natural product flustramine C from the bryozoan Flustra foliacea was
      synthesized in five steps and 38% yield starting from Nb-methyltryptamine. The
      key step is the biomimetic oxidation of the natural product
      deformylflustrabromine causing selective 1,2-rearrangement of the inverse prenyl
      group. By 1H,15N HMBC experiments, it is unambiguously shown that the reaction
      with t-BuOCl commences with chlorination of the side chain nitrogen.
      Deformylflustrabromine itself was synthesized via Danishefsky inverse
      prenylation. [reaction: see text].

PMID- 17217284
TI  - Total synthesis of (+/-)-strychnine via a [4 + 2]-cycloaddition/rearrangement
      cascade.
AB  - A new strategy for the synthesis of the Strychnos alkaloid (+/-)-strychnine has
      been developed and is based on an intramolecular [4 + 2]
      cycloaddition/rearrangement cascade of an indolyl-substituted amidofuran. The
      critical D-ring was assembled by an intramolecular palladium-catalyzed enolate
      driven cross-coupling of an N-tethered vinyl iodide. [reaction: see text].

PMID- 17217286
TI  - Alpha,alpha'-annulation of 2,6-prenyl-substituted cyclohexanone derivatives with
      malonyl chloride: application to a short synthesis of (+/-)-clusianone. Formation
      and rearrangement of a biogenetic-like intermediate.
AB  - Conditions were found for the successful Effenberger alpha,alpha'-annulation of
      3,3-dimethyl-2,4,6-triprenyl cyclohexanone silyl enol ethers with malonyl
      chloride to give the corresponding bicyclo[3.3.1]nonane-trione in 35% yield, this
      result allowing a short synthesis of (+/-)-clusianone. An isomeric rearranged
      bicyclo[3.3.1]nonane-trione was also isolated in 25% yield, and changing the
      Lewis acid resulted in formation of a lavandulyl-substituted phloroglucinol
      derivative in 38% yield. The mechanism of formation of these two last products
      mimics the biogenetic pathway to PPAPs. [reaction: see text].

PMID- 17217287
TI  - Przewalskin B, a novel diterpenoid with an unprecedented skeleton from Salvia
      przewalskii maxim.
AB  - Przewalskin B (1), a novel diterpenoid possessing a unique skeleton, was isolated
      from a Chinese medicinal plant Salvia przewalskii. Its structure and relative
      stereochemistry were elucidated by extensive NMR analysis and a single-crystal X
      ray study. A possible biosynthetic pathway for 1 was proposed. Compound 1
      exhibited modest anti-HIV-1 activity with EC50 = 30 microg/mL. [structure: see
      text].

PMID- 17217288
TI  - First enantiospecific total synthesis of the important biogenetic intermediates,
      (+)-polyneuridine and (+)-polyneuridine aldehyde, as well as 16-epi-vellosimine
      and macusine A.
AB  - The first enantiospecific total synthesis of the alkaloids 16-epi-vellosimine
      (1), (+)-polyneuridine (2), (+)-polyneuridine aldehyde (3), and macusine A (4) is
      reported. The key oxidation was accomplished with the Corey-Kim reagent to
      provide the important biogenetic intermediates, 16-epi-vellosimine (1) and
      polyneuridine aldehyde (3), the latter of which is required for the conversion of
      the sarpagan skeleton into the ajmalan system in the biosynthesis of
      quebrachidine. [reaction: see text].

PMID- 17217289
TI  - Large-scale synthesis of immunoactivating natural product, pristane, by
      continuous microfluidic dehydration as the key step.
AB  - An efficient protocol of dehydration was developed under microfluidic conditions.
      The method was applied to a multikilogram synthesis of pristane, a biologically
      important natural product, which is now widely used as an adjuvant for monoclonal
      antibody production. [reaction: see text].

PMID- 17217290
TI  - Multicomponent synthesis of 3-indolepropionic acids.
AB  - A three-component one-pot procedure (3-MC) was developed to assemble 3
      indolepropionic acids from commercially available materials. This new methodology
      affords the title compounds in high yields and without the use of chromatography.
      [reaction: see text].

PMID- 17217291
TI  - Synthesis of 2-epi-amphidinolide E: an unexpected and highly selective
      C(2)inversion during an esterification reaction.
AB  - A synthesis of 2-epi-amphidinolide E (1) has been accomplished via an unexpected
      and highly diastereoselective C(2) stereochemical inversion during the modified
      Yamaguchi esterification of alcohol 4b and Fe(CO)3-complexed dienoic acid 7.
      [reaction: see text].

PMID- 17217292
TI  - Surfactant-type Bronsted acid catalyzed dehydrative nucleophilic substitutions of
      alcohols in water.
AB  - A protocol for the dehydrative nucleophilic substitution of benzyl alcohols with
      a variety of carbon- and heteroatom-centered nucleophiles using
      dodecylbenzenesulfonic acid (DBSA) as a surfactant-type Bronsted acid catalyst in
      water has been developed. The reaction system can be applied to the
      stereoselective C-glycosylation of 1-hydroxy sugars in water. [reaction: see
      text].

PMID- 17217293
TI  - Fluorescence sensing and binding behavior of aminobenzenesulfonamidoquinolino
      beta-cyclodextrin to Zn2+.
AB  - A water-soluble fluorescent zinc sensor which binds strongly to Zn2+ (log K =
      12.4) was successfully synthesized under physiological conditions. This sensor
      exhibits a good fluorescence response to Zn2+ over a wide pH range in water.
      Under the same conditions, several metal ions commonly present in a physiological
      environment, such as Na+, K+, Ca2+, Mg2+, Mn2+, Fe2+, and Co2+, showed little
      interference to the fluorescence response to Zn2+. [structure: see text]

PMID- 17217294
TI  - Chiral aggregates formed from methylated tetraenoic fatty acids: formation of
      both antipodes of chiral aggregates from a single enantiomer and time-dependent
      stereomutation.
AB  - Formation and behaviors of chiral aggregates of methylated tetraenoic fatty acids
      (TE-FAs) were reported. In the C-24 TE-FA series, the aggregate prepared by
      dispersing an ethanol stock solution of C-24 TE-FA 1b into sodium phosphate
      buffer gave a strong positive Cotton effect, whereas the aggregate prepared from
      a methanol stock solution gave a negative Cotton effect. In the C-20 TE-FA
      series, the aggregate prepared from an ethanol stock solution of C-20 TE-FA 2b
      exhibited time-dependent chirality inversion. [see text].

PMID- 17217295
TI  - Synthesis of boron cluster lipids: closo-dodecaborate as an alternative
      hydrophilic function of boronated liposomes for neutron capture therapy.
AB  - We succeeded in the synthesis of the double-tailed boron cluster lipids 4a-c and
      5a-c, which have a B12H11S moiety as a hydrophilic function, by S-alkylation of
      B12H11SH (BSH) with bromoacetyl and chloroacetocarbamate derivatives of
      diacylglycerols for a liposomal boron delivery system on neutron capture therapy.
      Calcein encapsulation experiments revealed that the liposomes, prepared from the
      boron cluster lipid 4b, DMPC, PEG-DSPE, and cholesterol, are stable at 37 degrees
      C in FBS solution for 24 h. [reaction: see text].

PMID- 17217296
TI  - Total synthesis of bistramide A.
AB  - An asymmetric synthesis of the marine metabolite bistramide A is reported. The
      synthesis relies on the utility of three different organosilane reagents to
      construct all principle fragments and 8 of the 11 stereogenic centers of the
      natural product. [structure: see text].

PMID- 17217297
TI  - Heavier alkaline Earth amides as catalysts for the Tischenko reaction.
AB  - Homoleptic heavier alkaline earth amides, M{N(SiMe3)2}2(THF)2 (M = Ca, Sr, and
      Ba) are reported as precatalysts for the dimerization of aldehydes to the
      analogous carboxylic esters (Tischenko reaction). [reaction: see text].

PMID- 17217298
TI  - Enzyme-catalyzed enantioselective diaryl ketone reductions.
AB  - The synthesis of diarylmethanols via the reduction of a range of substituted
      benzophenone and benzoylpyridine derivatives with ketoreductase enzymes (KREDs)
      has afforded chiral products with high yield (>90%) and ee (up to >99%). Ortho,
      meta, and para substitutions with a variety of electron-donating, electron
      withdrawing, and halogen groups were examined. Substitution at the ortho position
      and/or highly electronically dissymmetric molecules were not required for good
      selectivity, as is the case with conventional chemical catalyst reductions.
      [reaction: see text].

PMID- 17217299
TI  - Enantioselective total synthesis of (+)-gliocladin C.
AB  - The first total synthesis of gliocladin C, a fungal-derived marine alkaloid
      containing a rare trioxopiperazine fragment, is reported. This asymmetric
      synthesis establishes the absolute configuration of this structurally novel
      natural product. [reaction: see text].

PMID- 17217300
TI  - Anionic four-electron donor-based palladacycles as catalysts for addition
      reactions of arylboronic acids with alpha,beta-unsaturated ketones, aldehydes,
      and alpha-ketoesters.
AB  - Anionic four-electron donor-based palladacycle-catalyzed 1,4-additions of
      arylboronic acids with alpha,beta-unsaturated ketones and 1,2-additions of
      arylboronic acids with aldehydes and alpha-ketoesters are described. Our study
      demonstrated that palladacycles were highly efficient, practical catalysts for
      these addition reactions. The work described here not only opened a new paradigm
      for the application of palladacycles, but may also pave the road for other
      metalacycles as practically useful catalysts for such addition reactions
      including asymmetric ones. [reaction: see text].

PMID- 17217301
TI  - Rhodium(I)-catalyzed allenic carbocyclization reaction affording delta- and
      epsilon-lactams.
AB  - This letter extends the scope of the rhodium(I)-catalyzed allenic Alder-ene
      carbocyclization reaction to the preparation of delta- and epsilon-lactams from
      amides. A variety of allenic propiolamides were cycloisomerized to give a number
      of unsaturated delta-lactams. In addition, allenic propargylamides give good
      yields of the corresponding epsilon-lactams. Formation of lactams possessing
      these ring sizes has rarely been accomplished via transition-metal-catalyzed
      carbon-carbon bond forming strategies. Thus, this approach provides an
      alternative strategy for synthesizing these substructures. [reaction: see text].

PMID- 17217302
TI  - Amine-promoted, organocatalytic aziridination of enones.
AB  - A novel method is presented using N-N ylides (prepared by in situ amination of a
      tertiary amine) for the aziridination of a range of enone systems. The amine may
      be used sub-stoichiometrically, and promising levels of enantioselectivity are
      observed with quinine as promoter. [reaction: see text].

PMID- 17217303
TI  - A convenient, NMR-based method for the analysis of diastereomeric mixtures of
      pseudoephedrine amides.
AB  - Amides of pseudoephedrine and ephedrine are shown to undergo highly
      stereospecific, invertive cyclization to form 4,5-dihydro-3,4-dimethyl-5-phenyl
      1,3-oxazolium triflate derivatives in the presence of triflic anhydride-pyridine.
      1H NMR spectra of the unpurified reaction products are remarkably clean, with
      sharp, well-defined peaks, and allow for rapid assessment of the diastereomeric
      purities of the starting amides. [reaction: see text].

PMID- 17217304
TI  - Enantioselective total synthesis of (-)-erinacine B.
AB  - The first enantioselective total synthesis of (-)-erinacine B has been achieved.
      Our approach features convergent construction of the 5-6-7 tricyclic cyathane
      core system via chiral building blocks prepared using asymmetric catalysis
      developed by us and highly stereoselective construction of all stereogenic
      centers in the aglycon. [reaction: see text].

PMID- 17217306
TI  - Platinum(II)-catalyzed cyclizations forming quaternary carbon centers, using
      enesulfonamides, enecarbamates, or enamides as nucleophiles.
AB  - Cyclic enesulfonamides, enecarbamates, or enamides tethered to an alkyne cyclize
      readily with use of platinum(II) chloride. This reaction generates quaternary
      substituted carbon centers within simple spiro-fused or more complex tri- and
      tetracyclic heterocyclic ring systems. The yields for this process range from 50%
      to 83%. [reaction: see text].

PMID- 17217305
TI  - Two palladium-catalyzed domino reactions from one set of substrates/reagents:
      efficient synthesis of substituted indenes and cis-stilbenoid hydrocarbons from
      the same internal alkynes and hindered Grignard reagents.
AB  - Two types of domino reactions from the same internal alkynes and hindered
      Grignard reagents based on carbopalladation, Pd-catalyzed cross-coupling
      reaction, and a C-H activation strategy are described. The realization of these
      domino reactions relied on the control of the use of the ligand and the reaction
      temperature. Our study provides efficient access to useful polysubstituted
      indenes and cis-substituted stilbenes and may offer a new means of development of
      tandem/domino reactions in a more efficient way. [reaction: see text].

PMID- 17217307
TI  - Tandem oxidation of allylic and benzylic alcohols to esters catalyzed by N
      heterocyclic carbenes.
AB  - N-heterocyclic carbenes catalyze the oxidation of allylic, propargylic, and
      benzylic alcohols to esters with manganese(IV) oxide in excellent yields. A
      variety of ester derivatives can be synthesized, including protected
      carboxylates. This one-pot tandem oxidation represents the first organocatalytic
      oxidation of alcohols to esters. Saturated esters can also be accessed from
      aldehydes using this method. Through the utilization of a chiral catalyst, the
      acyl-heteroazolium intermediate becomes a chiral acylating agent, which can
      desymmetrize meso-1,2-diols. [reaction: see text].

PMID- 17217308
TI  - Stepwise acid-promoted double-Michael process: an alternative to Diels-Alder
      cycloadditions for hindered silyloxydiene-dienophile pairs.
AB  - The hindered diene 1 reacts with 3-methylcyclohexenone 6 catalyzed by triflimide
      to produce the Mukaiyama Michael product 7 (low-temperature quenching) or the
      [4+2] cycloadduct 8 (quenching at 0 degrees C). Reaction of the hindered diene 23
      with 2-methylcyclohexenone 12 with 5:1 AlBr3:AlMe3 afforded a 71% yield of a
      1.9:1 mixture of two cycloadducts. Hydrolysis of the major isomer gave the dione
      27', a model for the BCD ring system of pentacyclic triterpenes. [reaction: see
      text].

PMID- 17217311
TI  - Phosphoramidate pronucleotides: a comparison of the phosphoramidase substrate
      specificity of human and Escherichia coli histidine triad nucleotide binding
      proteins.
AB  - To facilitate the delivery of nucleotide-based therapeutics to cells and tissues,
      a variety of pronucleotide approaches have been developed. Our laboratory and
      others have demonstrated that nucleoside phosphoramidates can be activated
      intracellularly to the corresponding 5'-monophosphate nucleotide and that
      histidine triad nucleotide binding proteins (Hints) are potentially responsible
      for their bioactivation. Hints are conserved and ubiquitous enzymes that
      hydrolyze phosphoramidate bonds between nucleoside 5'-monophosphate and an amine
      leaving group. On the basis of the ability of nucleosides to quench the
      fluorescence of covalently linked amines containing indole, a sensitive,
      continuous fluorescence-based assay was developed. A series of substrates linking
      the naturally fluorogenic indole derivatives to nucleoside 5'-monophosphates were
      synthesized, and their steady state kinetic parameters of hydrolysis by human
      Hint1 and Escherichia coli hinT were evaluated. To characterize the elemental and
      stereochemical effect on the reaction, two P-diastereoisomers of adenosine or
      guanosine phosphoramidothioates were synthesized and studied to reveal a 15-200
      fold decrease in the specificity constant (kcat/Km) when the phosphoryl oxygen is
      replaced with sulfur. While a stereochemical preference was not observed for E.
      coli hinT, hHint1 exhibited a 300-fold preference for d-tryptophan
      phosphoramidates over l-isomers. The most efficient substrates evaluated to date
      are those that contain the less sterically hindering amine leaving group,
      tryptamine, with kcat and Km values comparable to those found for adenosine
      kinase. The apparent second-order rate constants (kcat/Km) for adenosine
      tryptamine phosphoramidate monoester were found to be 107 M-1 s-1 for hHint1 and
      106 M-1 s-1 for E. coli hinT. Both the human and E. coli enzymes preferred purine
      over pyrimidine analogues. Consistent with observed hydrogen bonding between the
      2'-OH group of adenosine monophosphate and the active site residue, Asp43, the
      second-order rate constant (kcat/Km) for thymidine tryptamine phosphoramidate was
      found to be 3-4 orders of magnitude smaller than that for uridine tryptamine
      phosphoramidate for hHint1 and 2 orders of magnitude smaller than that for E.
      coli hinT. Ara-A tryptamine phosphoramidate was, however, shown to be a good
      substrate with a specificity constant (kcat/Km) only 10-fold lower than the value
      for adenosine tryptamine phosphoramidate. Consequently, nucleoside
      phosphoramidates containing unhindered primary amines and either an alpha or beta
      2'-OH group should be easily bioactivated by Hints with efficiencies rivaling
      those for the 5'-monophosphorylation of nucleosides by nucleoside kinases. The
      differential substrate specificity observed for human and E. coli enzymes
      represents a potential therapeutic rationale for the development of selective
      antibiotic phosphoramidate pronucleotides.

PMID- 17217312
TI  - Polymer nanoparticles for immunotherapy from encapsulated tumor-associated
      antigens and whole tumor cells.
AB  - Encapsulation of tumor-associated antigens (TAA) in polymer nanoparticles is a
      promising approach to increasing the efficiency of antigen (Ag) delivery for
      antitumor vaccines. We optimized a polymer preparation method to deliver both
      defined tumor-associated proteins and the complex mixtures of tumor Ags present
      in tumors. Tumor Ags were encapsulated in a biodegradable, 50:50 poly(D,L-lactide
      co-glycolide) copolymer (PLGA) by emulsification and solvent extraction. Two
      particular Ags were studied, gp100 (a melanoma-associated antigen) and ovalbumin
      (OVA), as well as mixtures of proteins and lysates of tumor cells. The efficiency
      of encapsulation was measured by protein assays of dissolved nanoparticles. Ag
      stability after release from nanoparticles was verified by SDS-acrylamide gel
      electrophoresis and Western blot analysis. Molecular weight and protein loading
      interact to define the encapsulation efficiency and release rate of nanoparticles
      formulated from 50:50 PLGA. A midrange molecular weight polymer had more
      desirable release properties at 100 mg/mL than at 50 mg/mL protein loading,
      indicating the need for optimization of nanoparticle formulation for preparations
      with different particle loadings. Mixtures of proteins derived from cell lysates
      were reliably encapsulated into nanoparticles, which released the spectrum of
      proteins contained in lysates. Antigenic proteins were co-encapsulated with cell
      lysate and released from nanoparticles; these Ags retained their antigenicity and
      functioned better than soluble Ags when tested in in vitro assays of T cell
      cytokine formation and in vivo tumor vaccination challenge.

PMID- 17217313
TI  - Cost effectiveness of imatinib mesylate in the treatment of advanced
      gastrointestinal stromal tumours.
AB  - BACKGROUND AND OBJECTIVE: Imatinib mesylate is the first effective therapy for
      advanced unresectable gastrointestinal stromal tumours (GIST). Adoption of this
      therapy in clinical practice is partly dependent on reimbursement by third-party
      payers in many countries. The objective of this study was to estimate the cost
      effectiveness of imatinib mesylate in the treatment of GIST. METHODS: A cost
      effectiveness model of GIST treatment was developed. Long- term survival and
      duration of imatinib mesylate benefit were projected by fitting curves to 52
      month follow-up data from a phase II clinical trial of imatinib and projecting
      weekly probabilities of survival and continued treatment over 10 years. Weekly
      cost estimates in 2005 US dollars included cost of imatinib mesylate 400 mg/day
      ($US685), other medical services for imatinib mesylate-treated patients ($US359)
      and palliative care for patients in the end stage of GIST ($US2575). Utility
      associated with successful treatment was estimated at 0.935 and that of treatment
      failure and progressive disease at 0.875. Costs, life-years and quality- adjusted
      life-years (QALYs) were calculated over the 10-year time horizon and discounted
      to treatment initiation at an annual rate of 3%. RESULTS: Imatinib mesylate
      therapy for unresectable GIST was projected to increase life expectancy to 5.8
      years, an increase of 2.7 years over the control group. This translated into an
      increase of 1.9 QALYs at a marginal cost of $US74 369, yielding a cost
      effectiveness ratio of $US38 723 per QALY. Cost effectiveness was not very
      sensitive to model parameters other than the cost of imatinib mesylate itself.
      CONCLUSION: The cost effectiveness of imatinib mesylate in the treatment of GIST
      is within the commonly accepted range for life-saving interventions, based on US
      data.

PMID- 17217314
TI  - Determining factors in the prescription of moxifloxacin in exacerbations of
      chronic bronchitis in the primary-care setting.
AB  - OBJECTIVE: To describe the characteristics of patients and exacerbations that may
      determine the choice of an antibacterial in exacerbations of chronic bronchitis
      (ECB). METHODS: This was a multicentre, observational study in ECB. A group of
      225 primary-care practitioners were randomly selected to include 1007 patients. A
      logistic regression model was used to identify the characteristics of the
      physicians, patients and exacerbations associated with the choice of an
      antibacterial. RESULTS: The mean age of the patients was 67.6 years (+/- SD 11)
      and 72.1% were male. In 91.4% of patients, the exacerbation was type I or II
      according to Anthonisen's classification. Most exacerbations (68.2%) were treated
      with moxifloxacin while only 31.8% were treated with other antibacterials. The
      more experienced practitioners (those with the longest professional careers and
      those who had higher numbers of patient-visits for chronic bronchitis) prescribed
      moxifloxacin more frequently (per each year of experience: OR 1.05; 95% CI 1.02,
      1.07; per each additional patient-visit per week: OR 1.02; 95% CI 1.003, 1.04).
      The probability of receiving moxifloxacin increased with the severity of baseline
      dyspnoea (OR 1.94; 95% CI 1.27, 2.96) and decreased in smokers (OR 0.54; 95% CI
      0.36, 0.81) and in patients receiving oral corticosteroids (OR 0.61; 95% CI 0.41,
      0.90). CONCLUSIONS: Prescription of moxifloxacin in primary care is significantly
      associated with more years of physician practice and with a higher severity of
      disease. The use of oral corticosteroids in exacerbations is commonly associated
      with other antibacterials (non-quinolones), either to improve antibacterial
      efficacy or because of doubtful bacterial aetiology, thus the preference for a
      narrow-spectrum antibacterial combined with an anti-inflammatory drug.

PMID- 17217315
TI  - Comparative cost-benefit analyses of paricalcitol and calcitriol in stage 4
      chronic kidney disease from the perspective of a health plan.
AB  - BACKGROUND AND OBJECTIVE: Substantial data for the relative costs of
      hospitalisation in paricalcitol- and calcitriol-treated patients with chronic
      kidney disease stage 4 do not exist. The objective of this study was to compare
      the cost benefit of paricalcitol and calcitriol therapies in chronic kidney
      disease stage 4 from the perspective of a healthcare payer. METHODS: A range of
      methods were used to estimate the relative costs of hospitalisation in
      paricalcitol- and calcitriol-treated patients with chronic kidney disease stage
      4, extrapolated from observed differences in hospitalisation costs in stage 5
      patients. Different values and approaches were used to show a range of values and
      to show the specific hospitalisation benefit in terms of the all-cause
      hospitalisation rate and number of all-cause hospital days. RESULTS: The annual
      dollar impact of use of paricalcitol instead of calcitriol on all-cause hospital
      admissions was calculated to be a reduction of $US1220-$US4476 and for all-cause
      number of hospital days a reduction of $US1816-$US8776. A total of 42 cost
      comparison estimates were generated to compare the cost benefit of calcitriol or
      paricalcitol. Of these 42 comparisons, 35 showed that the total cost of
      paricalcitol was lower than the total cost of calcitriol therapy. The cost
      advantage of paricalcitol over calcitriol substantially increased as patients
      progressed toward dialysis. CONCLUSION: Cost analyses suggest that paricalcitol
      treated patients have a lower total cost than calcitriol-treated patients.

PMID- 17217316
TI  - Retrospective evaluation of adverse drug reactions induced by nonsteroidal anti
      inflammatory drugs.
AB  - BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are among
      the most widely prescribed drugs, and their use can be complicated by the
      development of adverse drug reactions (ADRs). The aim of this study was to assess
      the frequency of NSAID-induced ADRs in hospitalised patients in the Clinical
      Divisions of the Catanzaro and Cosenza hospitals. METHODS: We retrospectively
      analysed NSAID-induced ADRs after evaluating all ADRs recorded by the Clinical
      Divisions of the Catanzaro and Cosenza hospitals over a 10-year period, from
      January 1995 to December 2004. RESULTS: NSAIDs were found to be responsible for
      55.2% of the episodes of ADRs overall. Diclofenac and aspirin (acetylsalicylic
      acid) were the drugs most frequently involved in the development of ADRs, while
      the skin was the body system most susceptible to NSAID-induced ADRs (43%). We
      determined that the drug-ADR relationship was probable in 62% of the reports;
      withdrawal of NSAID therapy led to a resolution of the clinical features of ADRs
      in 86% of episodes. CONCLUSION: NSAID therapy represents a common cause of ADRs
      in hospitalised patients. Their use should be carefully considered, especially in
      the presence of polydrug therapy.

PMID- 17217317
TI  - Clinical effectiveness of quetiapine in children and adolescents with Tourette's
      syndrome : a retrospective case-note survey.
AB  - BACKGROUND AND OBJECTIVE: Tourette's syndrome is a relatively common biological
      genetic disorder with a broad spectrum of neurobehavioural manifestations.
      Unfortunately, treatment of the condition is often unsatisfactory and all
      available drugs are associated with potential adverse effects. We therefore aimed
      to investigate the efficacy of quetiapine, a newer atypical antipsychotic, in the
      treatment of children and adolescents with Tourette's syndrome. METHODS: This was
      a retrospective study carried out in outpatient clinics. Twelve patients aged 8
      18 years with Tourette's syndrome (diagnosed according to Diagnostic and
      Statistical Manual IV criteria) who were receiving quetiapine therapy and had no
      diagnosis of epilepsy, major depression or psychotic disorder, were included in
      the study. The main outcome measure was the Yale Global Tic Severity Scale
      (YGTSS) score. RESULTS: The initial dose of quetiapine was 25 mg/day, but the
      mean dose was increased to 114.6 +/- 51.6 mg/day and 175.0 +/- 116.8 mg/day at
      the fourth and eighth weeks of treatment, respectively. The YGTSS score, which
      was 21.6 +/- 4.0 at baseline, showed significant decreases at 4 and 8 weeks
      (reducing to 7.5 +/- 7.4 and 5.6 +/- 8.1, respectively; p < 0.003). Routine
      laboratory parameters and serum prolactin level were all normal and did not
      change throughout treatment. Mild but significant increases in both bodyweight
      and body mass index at 4 and 8 weeks compared with baseline were observed.
      CONCLUSION: Other than causing mild weight gain, quetiapine appears to be an
      effective, safe and well tolerated drug in children and adolescents with
      Tourette's syndrome.

PMID- 17217318
TI  - Monophasic estrogen-progestogen therapy and sexuality in postmenopausal women.
AB  - OBJECTIVE: This study aimed to evaluate the effects of monophasic estrogen
      progestogen therapy on the sexuality and climacteric symptoms of postmenopausal
      women. PATIENTS AND METHODS: A prospective, randomised, double-blind, crossover,
      placebo-controlled, single-centre study was carried out over a total of 12
      consecutive months in 40 postmenopausal women with an intact uterus who had no
      contraindications to hormone therapy. Patients received 17beta-estradiol 2mg in
      combination with norethisterone acetate 1mg (Cliane) daily for 6 months or one
      placebo tablet daily for 6 months. The tablets were identical in appearance.
      After 6 months, the groups were crossed over and the patients were followed up
      for another 6 months. The groups were homogenous with respect to age, height,
      bodyweight, body mass index and race. For the statistical analysis, the group
      receiving hormone therapy was referred to as group A and the placebo group was
      designated group B, irrespective of the placebo/hormone therapy sequence.
      RESULTS: In group A there were fewer hot flashes (F=22.85, p<0.01) and an
      improvement in sexual interest (F=5.55, p<0.05). The sequence in which the
      medication was received resulted in a statistically significant difference with
      respect to dyspareunia (F=9.65, p<0.01) and satisfaction with the duration of
      penetration (F=6.58, p<0.05). In the intrapatient analysis of variation with
      respect to orgasmic capability and the presence of dialogue with partner
      regarding the couple's sexual life, whether the placebo was taken prior to or
      following hormone therapy was significant (F=17.12, p<0.001 and F=7.10, p<0.05,
      respectively). CONCLUSIONS: Monophasic estrogen-progestogen therapy has a
      beneficial effect on sexuality and on hot flashes in postmenopausal women.

PMID- 17217319
TI  - Medical costs of chronic musculoskeletal pain in Italy.
AB  - BACKGROUND AND OBJECTIVES: Musculoskeletal system problems are responsible for
      more than two-thirds of painful conditions in primary care. However, only one
      published study, conducted in Finland, has analysed the costs of managing
      musculoskeletal pain as a whole in primary care. This study analysed the costs of
      diagnosing and treating chronic musculoskeletal pain in primary care in Italy. A
      secondary aim of the study was to assess the impact of different drug treatment
      patterns on medical costs associated with musculoskeletal pain. METHODS: Chronic
      pain of musculoskeletal origin was defined as continuous or recurrent pain
      persisting over 3 months with involvement of the musculoskeletal system, i.e.
      arising from primary musculoskeletal disorders or from the late consequences of
      external events (injuries, medical care or surgery). A total of 52 general
      practitioners (GPs) recruited 581 patients. We focussed on the differences
      between patients treated (410) and not treated (171) with drugs. Within the
      treated group, we also analysed subgroups given non-selective NSAID-based therapy
      (subgroup A, 169 patients) or cyclo-oxygenase-2 (COX-2) inhibitor-based therapy
      (subgroup B, 52 patients). RESULTS: The annual average cost of treating a patient
      with chronic musculoskeletal pain was euro 212.60. Hospital admissions and GP
      consultations were the largest cost components, both accounting for around a
      quarter of the total cost. Not surprisingly, the treated group included older
      patients, who had more co-morbidities and more severe pain. This was associated
      with annual costs more than four times those of untreated patients (euro 274.50
      vs euro 63.90, respectively). Subgroups A and B did not differ with respect to
      major demographic and clinical variables except in relation to mean age (63 vs 70
      years, respectively; p=0.037). They had similar per-patient costs (euro 186.20 vs
      euro 172.90), although these totals comprised a different mix of components.
      CONCLUSION: The analysis showed that the annual average cost of treatment of
      chronic musculoskeletal pain in Italy varied considerably depending on whether
      drug treatment was used. COX-2 inhibitors and traditional NSAIDs had similar per
      patient costs, although this similarity stemmed from a different mix of
      components.

PMID- 17217320
TI  - Natural remedies for scleroderma.
AB  - Scleroderma is an autoimmune disease of the connective tissue characterized by
      fibrosis and thickening of various tissues. It can be limited to the skin or
      affect multiple organs, and its course ranges from slowly to rapidly progressive.
      Penicillamine, glucocorticoids, and other drugs are used to treat scleroderma,
      but none of these treatments has a high degree of efficacy. This article reviews
      several promising natural treatments for scleroderma, including para-aminobenzoic
      acid, vitamin E, vitamin D, evening primrose oil, estriol, N-acetylcysteine,
      bromelain, and an avocado/soybean extract.

PMID- 17217321
TI  - Natural treatment of chronic rhinosinusitis.
AB  - Chronic rhinosinusitis (CRS) is one of the most common long-term illnesses in the
      United States, affecting approximately 14 percent of the population. CRS is a
      challenging condition to treat, partly due to its multifaceted, poorly understood
      pathophysiology. Treatment goals include maintaining open drainage and decreasing
      inflammation while improving tissue integrity and limiting causative factors.
      This review covers the etiology, pathology, and diagnosis of CRS, as well as
      mainstream and alternative treatments. Discussion of alternative therapeutics
      includes nutrients and botanicals (ascorbic acid, bromelain, N-acetylcysteine,
      quercetin, undecylenic acid, and Urtica dioica and other herbal medicines) and
      procedures (nasal irrigation and naso-sympatico treatments). The influences of
      diet and air quality on CRS are also discussed.

PMID- 17217322
TI  - A comprehensive review of the safety and efficacy of bioidentical hormones for
      the management of menopause and related health risks.
AB  - Numerous forms of estrogens and progestins are utilized for the treatment of
      menopausal complaints and associated conditions that occur temporally. Although
      known to be different with respect to molecular structure, receptor affinity,
      metabolism, and other physiological traits, most have been treated as if they
      were clinically identical. The majority of these hormone preparations, commonly
      referred to as hormone replacement therapy (HRT), should perhaps be more aptly
      referred to as hormone substitution therapy, as most of the therapies utilized do
      not exactly match those produced in the body. Research indicates these synthetic
      hormones vary clinically in safety and efficacy. As such, women and their
      physicians have, in increasing numbers, been opting for the use of bioidentical
      hormones; i.e., those that match the structure and function of hormones produced
      in the body. With greater utilization and research surrounding bioidentical
      hormones, the differences can now begin to be fully assessed and appreciated.
      This article reviews the disparities between synthetic and bioidentical estrogens
      and progestins/progesterone with respect to safety and efficacy; special
      attention is devoted to clinical outcomes in the breast, endometrium, bone,
      cardiovascular system, and brain. The studies reviewed suggest bioidentical
      progesterone does not have a negative effect on blood lipids or vasculature as do
      many synthetic progestins, and may carry less risk with respect to breast cancer
      incidence. Studies of both bioidentical estrogens and progesterone suggest a
      reduced risk of blood clots compared to non-bioidentical preparations.
      Bioidentical hormone preparations have demonstrated effectiveness in addressing
      menopausal symptoms. The author advocates for continued research on bioidentical
      hormones and concludes there is currently sufficient evidence to support their
      preferred use over that of their synthetic cousins.

PMID- 17217323
TI  - Biofeedback and other therapies for the treatment of urinary incontinence in the
      elderly.
AB  - Alternative therapies hold potential promise for the treatment of urinary
      incontinence in the elderly. Assessment and comparisons of the efficacies of such
      therapies have been hindered by a lack of standardized definitions of urinary
      incontinence in the study populations, lack of standardization of treatment
      protocols, inadequate sample sizes, and lack of blinding and appropriate
      controls. Biofeedback has been the most extensively studied therapy and may
      provide appropriate adjunctive or primary therapy for select individuals. Other
      potential therapies, such as acupuncture, hypnosis, and herbal therapies, have
      not been sufficiently examined to make definitive recommendations.

PMID- 17217324
TI  - Alpha-lipoic acid. Monograph.

PMID- 17217325
TI  - Benfotiamine. Monograph.

PMID- 17217326
TI  - New approaches in the therapy of cardiomyopathy in muscular dystrophy.
AB  - Cardiomyopathy is a frequent occurrence in muscular dystrophy, and heart disease
      in muscular dystrophy can contribute to both morbidity and mortality. A number of
      novel therapies are being developed for muscular dystrophy, and the efficacy of
      these therapies for heart disease is unknown. The most common X-linked recessive
      disease is Duchenne muscular dystrophy (DMD), which arises from defects in the
      dystrophin gene. Therapy specifically aimed at DMD is reviewed in the context of
      its projected effect on cardiomyopathy associated with DMD. Additionally, novel
      therapies are being pursued to treat specifically the cardiomyopathy of DMD.
      There is substantial genetic heterogeneity underlying the muscular dystrophies,
      and not all muscular dystrophy patients develop cardiomyopathy. A subset of
      muscular dystrophies may place patients at significantly greater risk of
      developing cardiomyopathy and cardiac rhythm disturbances. These disorders are
      discussed, highlighting recent studies and recommendations for therapy.

PMID- 17217327
TI  - Acute ischemic stroke: overview of recent therapeutic developments.
AB  - Stroke, a disorder encompassing all cerebrovascular accidents, is a public health
      problem of immense proportions across the globe. Therapeutic efforts are directed
      at three aspects: prevention, acute treatment, and rehabilitation. Preventative
      measures, which in many instances mirror those for cardiovascular disease, can
      achieve the greatest public health impact. Measures that enhance the recovery of
      neurologic function and reduce neurologic disability after stroke can also affect
      a large population of handicapped stroke survivors. In the past 10 years, the
      greatest changes have occurred in the field of acute stroke treatment. Ultra
      early-stage therapies with the potential to dramatically reverse severe
      neurologic deficits, or halt their progression, have caused a restructuring of
      the emergency care of neurologic patients. The parallels with the evolution of
      emergency treatment of acute coronary syndromes after 1970 are striking. This
      review focuses on aspects of stroke therapy that are either just entering, or
      soon to enter, current practice.

PMID- 17217328
TI  - Use of stents to treat intracranial cerebrovascular disease.
AB  - Intracranial atherosclerosis is a common cause of stroke. Although it has been
      recognized for decades, the lack of successful treatment strategies has limited
      clinical interest until recently. We review the natural history and
      pathophysiology of intracranial atherosclerosis. Vascular biomechanics are
      important to define differences between cerebral arteries and extracranial
      vessels and partly explain the technical challenges facing cerebral artery
      revascularization as compared with revascularization of coronary arteries.
      Pharmacological interventions to prevent stroke have had limited success, but
      technological developments offer improved methods for endovascular
      revascularization of symptomatic and asymptomatic cerebral artery stenosis.
      Identification of appropriate candidates for treatment also remains a challenge,
      and our knowledge about the natural history of the disease is limited. At this
      time, patients with significant intracranial stenosis should receive information
      on the benefits and risks of revascularization therapy. Determining which
      patients should undergo revascularization procedures will require carefully
      planned, randomized clinical trials.

PMID- 17217329
TI  - Cardiovascular risks of antiretroviral therapies.
AB  - The use of highly active antiretroviral therapy (HAART) has resulted in sustained
      reductions in mortality from HIV infection. In recent years, HAART has also been
      associated with metabolic complications that may increase patients'
      cardiovascular disease risk. Recent studies have begun to support a more complex
      interaction between HAART, HIV infection itself, and other traditional social and
      immunologic factors that may predispose patients to premature cardiovascular
      disease. Substantial progress has been made in the development of newer
      antiretroviral therapies that have a better metabolic profile with respect to
      dyslipidemia, hyperglycemia, and lipodystrophy. Optimal selection of
      metabolically neutral antiretroviral therapies, together with aggressive
      management of other modifiable coronary risk factors, may improve cardiovascular
      disease risk in the long term.

PMID- 17217330
TI  - Airway surface dehydration in cystic fibrosis: pathogenesis and therapy.
AB  - Cystic fibrosis (CF) lung disease reflects the failure of airways defense against
      chronic bacterial infection. Studies of CF cultures, transgenic mice, and CF
      patients suggest that the initiating event in CF airways disease pathogenesis is
      reduced airway surface liquid (ASL) volume, i.e., dehydration. CF ASL volume
      regulation depends on a single extracellular signaling system, ATP, which renders
      CF airways more vulnerable to disease-causing insults (e.g., viruses) than are
      normal airways, which regulate ASL volume by dual ATP and adenosine signaling
      pathways. Clinical studies have explored the hypothesis that treating the
      dehydration of CF airways will be therapeutically beneficial. Inhaled hypertonic
      saline osmotically draws water onto airway surfaces, improves mucus clearance and
      pulmonary function, and reduces acute exacerbations in CF patients. Thus,
      rehydration therapies may slow the progression of CF lung disease in patients
      with established bacterial infection and may prevent the onset of CF lung disease
      if initiated early in life.

PMID- 17217331
TI  - End-stage renal disease measures of quality.
AB  - During the past 35 years, there has been a geometric expansion of the population
      of patients receiving chronic dialysis therapy in the United States. As the size
      and associated costs of the dialysis population have grown, there has been a
      consistent and evolving emphasis on measuring and improving the quality of
      dialysis care. These efforts, aided by robust data collection vehicles, have
      translated into defined clinical performance measures; nevertheless, morbidity
      and mortality rates remain high for the dialysis population. Recently, attention
      has focused on whether improved outcomes could be obtained by paying physicians
      and dialysis providers on the basis of quality metrics. The feasibility, value,
      pitfalls, and appropriate quality metrics in a "payment-for-quality" program for
      dialysis care are currently under vigorous discussion.

PMID- 17217332
TI  - New therapeutic approaches for multiple sclerosis.
AB  - Although several therapies exist for multiple sclerosis (MS), the most common
      inflammatory demyelinating disease of the central nervous system (CNS), there
      remains a large unmet clinical need for more effective immunomodulatory
      treatments in this category of diseases and for interventions that address their
      neurodegenerative component, which is currently untreated. Progress in our
      understanding of the immunology of MS over the past 30 years has recently
      synergized with novel computational methods and emerging high-throughput
      technologies that characterize variations in DNA, RNA, proteins, and metabolites
      to usher in a period of intense pathophysiologic investigation. These efforts are
      beginning to define subsets of patients with different forms of demyelinating
      disease. This partitioning of patients will prove valuable as we begin to tailor
      immunotherapy to the underlying pathophysiologic processes of individual patients
      using current therapies, emerging treatments, and rational combinations of all of
      these treatments. Preventing the entry of lymphocytes into the CNS and modifying
      the nature of the immune response are treatment approaches that work in the
      inflammatory component of MS but have little or no effect on neurodegeneration.
      Two challenges confront us: to develop cocktails of therapies that shift the
      immune homeostasis of patients with MS toward a healthy profile, and to identify
      and modulate the activity of targets within the neurodegenerative component of
      MS.

PMID- 17217333
TI  - Cytokine therapy for Crohn's disease: advances in translational research.
AB  - Crohn's disease (CD) and ulcerative colitis (UC), the two idiopathic inflammatory
      bowel diseases (IBDs), affect almost two million individuals in North America and
      several million worldwide. Cytokines are important in the pathogenesis of CD, and
      their manipulation has successfully reduced disease severity and maintained
      remission. Following the discovery of novel cytokines and the role they may play
      in gut mucosal immunity, as well as the emergence of new concepts and changing
      paradigms in CD pathogenesis, the roles of several cytokines have been elucidated
      and tested in both preclinical animal models and clinical trials of patients with
      IBD. Complementary to this, proof of concept for new cytokine targets is rapidly
      developing, with the possibility of future cytokine-based therapies that may
      offer greater specificity and decreased toxicity for the treatment of CD. This
      review discusses novel concepts in CD pathogenesis and the roles of cytokines in
      the initiation and perpetuation of disease. In addition, we review applications
      of cytokine-based therapies in human clinical trials and preclinical animal
      studies. Finally, we discuss novel cytokine targets not yet investigated in vivo
      and describe their potential contribution to CD pathogenesis.

PMID- 17217334
TI  - Current concepts in AIDS pathogenesis: insights from the SIV/macaque model.
AB  - The pathogenesis of AIDS has proven to be quite complex and dynamic, with most of
      the critical events (e.g., transmission, CD4(+) T cell destruction) occurring in
      tissues that are not easily accessible for analysis. In addition, although the
      disease can progress over years, many critical events happen within the first few
      weeks of infection, when most patients are unaware that they are infected. The
      nonhuman primate model of AIDS has been used extensively to fill these gaps in
      our understanding of AIDS pathogenesis.

PMID- 17217336
TI  - Max is acetylated by p300 at several nuclear localization residues.
AB  - Max is a ubiquitous transcription factor with a bHLHZip [basic HLH (helix-loop
      helix) leucine zipper] DNA-binding/dimerization domain and the central component
      of the Myc/Max/Mad transcription factor network that controls cell growth,
      proliferation, differentiation and apoptotic cell death in metazoans. Max is the
      obligatory DNA-binding and dimerization partner for all the bHLHZip regulators of
      the Myc/Max/Mad network, including the Myc family of oncoproteins and the Mad
      family of Myc antagonists, which recognize E-box DNA elements in the regulatory
      regions of target genes. Max lacks a transcription regulatory domain and is the
      only member of the network that efficiently homodimerizes. Binding of Max
      homodimers to E-box elements suppresses the transcription regulatory functions of
      its network partners and of other non-network E-box-binding regulators. In
      contrast with its highly regulated partners, Max is a constitutively expressed
      and phosphorylated protein. Phosphorylation is, however, the only Max post
      translational modification identified so far. In the present study, we have
      analysed Max posttranslational modifications by MS. We have found that Max is
      acetylated at several lysine residues (Lys-57, Lys-144 and Lys-145) in mammalian
      cells. Max acetylation is stimulated by inhibitors of histone deacetylases and by
      overexpression of the p300 co-activator/HAT (histone acetyltransferase). The p300
      HAT also directly acetylates Max in vitro at these three residues. Interestingly,
      the three Max residues acetylated in vivo and in vitro by p300 are important for
      Max nuclear localization and Max-mediated suppression of Myc transactivation.
      These results uncover novel post-translational modifications of Max and suggest
      the potential regulation of specific Max complexes by p300 and reversible
      acetylation.

PMID- 17217337
TI  - In situ molecular identification of the Ntf4 MAPK expression sites in maturing
      and germinating pollen.
AB  - BACKGROUND INFORMATION: MAPKs (mitogen-activated protein kinases) are involved in
      the transduction of different signals in eukaryotes. They regulate different
      processes, such as differentiation, proliferation and stress response. MAPKs act
      through the phosphorylation cascade, being the last element that phosphorylates
      the final effector of the cell response. They are activated when their threonine
      and tyrosine residues are phosphorylated. Ntf4, a MAPK with a molecular mass of
      45 kDa, has been reported to be expressed in pollen and seeds. Biochemical
      studies have indicated that the expression and the activation of Ntf4 is
      regulated during pollen maturation, although an increase of the activation is
      observed when the pollen is hydrated, just at the beginning of the germination.
      However, nothing is known about its subcellular localization. RESULTS: In the
      present study, the in situ expression and subcellular localization of Ntf4 have
      been analysed during the tobacco pollen developmental pathway. Cryosections,
      freeze-substitution and cryo-embedding in Lowicryl K4M were used as processing
      techniques for subsequent immunofluorescence, immunogold labelling and in situ
      hybridization assays. During pollen maturation, Ntf4 showed an increase in
      expression, as demonstrated by in situ hybridization, and specific subcellular
      distributions. We found that the protein was expressed from mid bicellular pollen
      stage until the pollen was mature. In germinating pollen, the protein increased
      after the initiation of germination. Translocation of the protein to the nucleus
      was found at specific stages; the presence of Ntf4 in the nucleus was found in
      the last stage of the pollen maturation and in germinating pollen. Double
      immunofluorescence and immunogold labelling with anti-Ntf4 (AbC4) and anti-P-MAPK
      (phosphorylated MAPK) antibodies revealed the co-localization of both epitopes in
      the nucleus at late developmental stages. CONCLUSIONS: The temporal and spatial
      pattern of the expression sites of Ntf4 has been characterized during pollen
      development, indicating that Ntf4 is a 'late gene' that is upregulated during
      maturation and germination, with a possible role in the gametophytic function.
      The translocation of the Ntf4 protein from the cytoplasm to the nucleus at late
      pollen developmental stages, and its co-localization with the P-MAPK epitope in
      several nuclear sites, indicates a relationship between the Ntf4 nuclear
      translocation and its active state.

PMID- 17217338
TI  - Cell surface chondroitin sulfate glycosaminoglycan in melanoma: role in the
      activation of pro-MMP-2 (pro-gelatinase A).
AB  - We previously reported that CS (chondroitin sulfate) GAG (glycosaminoglycan),
      expressed on MCSP (melanoma-specific CS proteoglycan), is important for
      regulating MT3-MMP [membrane-type 3 MMP (matrix metalloproteinase)]-mediated
      human melanoma invasion and gelatinolytic activity in vitro. In the present
      study, we sought to determine if CS can directly enhance MT3-MMP-mediated
      activation of pro-MMP-2. Co-immunoprecipitation studies suggest that MCSP forms a
      complex with MT3-MMP and MMP-2 on melanoma cell surface. When melanoma cells were
      treated with betaDX (p-nitro-beta-D-xylopyranoside) to inhibit coupling of CS on
      the core protein, both active form and proform of MMP-2 were no longer co
      immunoprecipitated with either MCSP or MT3-MMP, suggesting a model in which CS
      directly binds to MMP-2 and presents the gelatinase to MT3-MMP to be activated.
      By using recombinant proteins, we determined that MT3-MMP directly activates pro
      MMP-2 and that this activation requires the interaction of the C-terminal domain
      of pro-MMP-2 with MT3-MMP. Activation of pro-MMP-2 by suboptimal concentrations
      of MT3-MMP is also significantly enhanced in the presence of excess C4S
      (chondroitin 4-sulfate), whereas C6S (chondroitin 6-sulfate) or low-molecular
      mass hyaluronan was ineffective. Affinity chromatography studies using CS
      isolated from aggrecan indicate that the catalytic domain of MT3-MMP and the C
      terminal domain of MMP-2 directly bind to the GAG. Thus the direct binding of pro
      MMP-2 with CS through the C-domain would present the catalytic domain of pro-MMP
      2 to MT3-MMP, which facilitates the generation of the active form of MMP-2. These
      results suggest that C4S, which is expressed on tumour cell surface, can function
      to bind to pro-MMP-2 and facilitate its activation by MT3-MMP-expressing tumour
      cells to enhance invasion and metastasis.

PMID- 17217339
TI  - Cross-talk between IRAK-4 and the NADPH oxidase.
AB  - Exposure of neutrophils to LPS (lipopolysaccharide) triggers their oxidative
      response. However, the relationship between the signalling downstream of TLR4
      (Toll-like receptor 4) after LPS stimulation and the activation of the oxidase
      remains elusive. Phosphorylation of the cytosolic factor p47phox is essential for
      activation of the NADPH oxidase. In the present study, we examined the hypothesis
      that IRAK-4 (interleukin-1 receptor-associated kinase-4), the main regulatory
      kinase downstream of TLR4 activation, regulates the NADPH oxidase through
      phosphorylation of p47phox. We show that p47phox is a substrate for IRAK-4.
      Unlike PKC (protein kinase C), IRAK-4 phosphorylates p47phox not only at serine
      residues, but also at threonine residues. Target residues were identified by
      tandem MS, revealing a novel threonine-rich regulatory domain. We also show that
      p47phox is phosphorylated in granulocytes in response to LPS stimulation. LPS
      dependent phosphorylation of p47phox was enhanced by the inhibition of p38 MAPK
      (mitogen-activated protein kinase), confirming that the kinase operates upstream
      of p38 MAPK. IRAK-4-phosphorylated p47phox activated the NADPH oxidase in a cell
      free system, and IRAK-4 overexpression increased NADPH oxidase activity in
      response to LPS. We have shown that endogenous IRAK-4 interacts with p47phox and
      they co-localize at the plasma membrane after LPS stimulation, using
      immunoprecipitation assays and immunofluorescence microscopy respectively. IRAK-4
      was activated in neutrophils in response to LPS stimulation. We found that
      Thr133, Ser288 and Thr356, targets for IRAK-4 phosphorylation in vitro, are also
      phosphorylated in endogenous p47phox after LPS stimulation. We conclude that IRAK
      4 phosphorylates p47phox and regulates NADPH oxidase activation after LPS
      stimulation.

PMID- 17217340
TI  - Temperature-, concentration- and cholesterol-dependent translocation of L- and D
      octa-arginine across the plasma and nuclear membrane of CD34+ leukaemia cells.
AB  - Delineating the mechanisms by which cell-penetrating peptides, such as HIV-Tat
      peptide, oligoarginines and penetratin, gain access to cells has recently
      received intense scrutiny. Heightened interest in these entities stems from their
      ability to enhance cellular delivery of associated macromolecules, such as genes
      and proteins, suggesting that they may have widespread applications as drug
      delivery vectors. Proposed uptake mechanisms include energy-independent plasma
      membrane translocation and energy-dependent vesicular uptake and internalization
      through endocytic pathways. In the present study, we investigated the effects of
      temperature, peptide concentration and plasma membrane cholesterol levels on the
      uptake of a model cell-penetrating peptide, L-octa-arginine (L-R8) and its D
      enantiomer (D-R8) in CD34+ leukaemia cells. We found that, at 4-12 degrees C, L
      R8 uniformly labels the cytoplasm and nucleus, but in cells incubated with D-R8
      there is additional labelling of the nucleolus which is still prominent at 30
      degrees C incubations. At temperatures between 12 and 30 degrees C, the peptides
      are also localized to endocytic vesicles which consequently appear as the only
      labelled structures in cells incubated at 37 degrees C. Small increases in the
      extracellular peptide concentration in 37 degrees C incubations result in a
      dramatic increase in the fraction of the peptide that is localized to the cytosol
      and promoted the binding of D-R8 to the nucleolus. Enhanced labelling of the
      cytosol, nucleus and nucleolus was also achieved by extraction of plasma membrane
      cholesterol with methyl-beta-cyclodextrin. The data argue for two, temperature
      dependent, uptake mechanism for these peptides and for the existence of a
      threshold concentration for endocytic uptake that when exceeded promotes direct
      translocation across the plasma membrane.

PMID- 17217341
TI  - Genetic population structure and contemporary dispersal patterns of a recent
      European invader, the Chinese mitten crab, Eriocheir sinensis.
AB  - Genetic studies of recently established populations are challenging because the
      assumption of equilibrium underlying many analyses is likely to be violated.
      Using microsatellites, we investigated determinants of genetic structure and
      migration among invasive European-Chinese mitten crab populations, applying a
      combination of traditional population genetic analyses and nonequilibrium
      Bayesian methods. Consistent with their recent history, invasive populations
      showed much lower levels of genetic diversity than a native Chinese population,
      indicative of recent bottlenecks. Population differentiation was generally low
      but significant and especially pronounced among recently established populations.
      Significant differentiation among cohorts from the same geographical location
      (River Thames) suggests the low effective population size and associated strong
      genetic drift that would be anticipated from a very recent colonization. An
      isolation-by-distance pattern appears to be driven by an underlying correlation
      between geographical distance and population age, suggesting that cumulative
      homogenizing gene flow reduces founder bottleneck-associated genetic
      differentiation between longer-established populations. This hypothesis was
      supported by a coalescent analysis, which supported a drift + gene flow model as
      more likely than a model excluding gene flow. Furthermore, admixture analysis
      identified several recent migrants between the UK and Continental European
      population clusters. Admixture proportions were significantly predicted by the
      volume of shipping between sites, indicating that human-mediated transport
      remains a significant factor for dispersal of mitten crabs after the initial
      establishment of populations. Our study highlights the value of nonequilibrium
      methods for the study of invasive species, and also the importance of evaluating
      nonequilibrium explanations for isolation by distance patterns.

PMID- 17217342
TI  - Linked vs unlinked markers: multilocus microsatellite haplotype-sharing as a tool
      to estimate gene flow and introgression.
AB  - We have explored the use of multilocus microsatellite haplotypes to study
      introgression from cultivated (Malus domestica) into wild apple (Malus
      sylvestris), and to study gene flow among remnant populations of M. sylvestris. A
      haplotype consisted of alleles at microsatellite loci along one chromosome. As
      destruction of haplotypes through recombination occurs much faster than loss of
      alleles due to genetic drift, the lifespan of a multilocus haplotype is much
      shorter than that of the underlying alleles. When different populations share the
      same haplotype, this may indicate recent gene flow between populations.
      Similarly, haplotypes shared between two species would be a strong signal for
      introgression. As the expected lifespan of a haplotype depends on the strength of
      the linkage, the length [in centiMorgans (cM)] of the haplotype shared contains
      information on the number of generations passed. This application of shared
      haplotypes is distinct from using haplotype-sharing to detect association between
      markers and a certain trait. We inferred haplotypes for four to eight
      microsatellite loci on Linkage Group 10 of apple from genotype data using the
      program phase, and then identified those haplotypes shared between populations
      and species. Compared with a Bayesian analysis of unlinked microsatellite loci
      using the program structure, haplotype-sharing detected a partially different set
      of putative hybrids. Cultivated haplotypes present in M. sylvestris were short (<
      1.5 cM), indicating that introgression had taken place many generations ago,
      except for two Belgian plants that contained a haplotype of 47.1 cM, indicating
      recent introgression. In the estimation of gene flow, F(ST) based on unlinked
      loci indicated small (0.032-0.058) but statistically significant differentiation
      between some populations only. However, various M. sylvestris haplotypes were
      shared in nearly all pairwise comparisons of populations, and their length
      indicated recent gene flow. Hence, all Dutch populations should be considered as
      one conservation unit. The added value of using sharing of multilocus
      microsatellite haplotypes as a source of population genetic information is
      discussed.

PMID- 17217343
TI  - Fine-scale spatial genetic structure and dispersal among spotted salamander
      (Ambystoma maculatum) breeding populations.
AB  - We examined fine-scale genetic variation among breeding aggregations of the
      spotted salamander (Ambystoma maculatum) to quantify dispersal, interpopulation
      connectivity and population genetic structure. Spotted salamanders rely on
      temporary ponds or wetlands for aggregate breeding. Adequate breeding sites are
      relatively isolated from one another and field studies suggest considerable adult
      site fidelity; therefore, we expected to find population structure and
      differentiation at small spatial scales. We used microsatellites to estimate
      population structure and dispersal among 29 breeding aggregations in Tompkins
      County, New York, USA, an area encompassing 1272 km(2). Bayesian and frequency
      based analyses revealed fine-scale genetic structure with two genetically defined
      demes: the North deme included seven breeding ponds, and the South deme included
      13 ponds. Nine ponds showed evidence of admixture between these two genetic
      pools. Bayesian assignment tests for detection of interpopulation dispersal
      indicate that immigration among ponds is common within demes, and that certain
      populations serve as sources of immigrants to neighbouring ponds. Likewise,
      spatial genetic correlation analyses showed that populations < or = 4.8 km
      distant from each other show significant genetic correlation that is not evident
      at higher scales. Within-population levels of relatedness are consistently larger
      than expected if mating were completely random across ponds, and in the case of a
      few ponds, within-population processes such as inbreeding or reproductive skew
      contribute significantly to differentiation from neighbouring ponds. Our data
      underscore the importance of these within-population processes as a source of
      genetic diversity across the landscape, despite considerable population
      connectivity. Our data further suggest that spotted salamander breeding groups
      behave as metapopulations, with population clusters as functional units, but
      sufficient migration among demes to allow for potential rescue and
      recolonization. Amphibian habitats are becoming increasingly fragmented and a
      clear understanding of dispersal and patterns of population connectivity for taxa
      with different ecologies and life histories is crucial for their conservation.

PMID- 17217344
TI  - Pleistocene isolation in the Northwestern Pacific marginal seas and limited
      dispersal in a marine fish, Chelon haematocheilus (Temminck & Schlegel, 1845).
AB  - The Northwestern Pacific has a unique tectonic and geographical history with
      several marginal seas separating Asia from the Pacific Ocean. During low sea
      level periods of Pleistocene glaciations, populations might have been isolated in
      three marginal seas: the Sea of Japan, East China Sea and South China Sea.
      Following postglacial sea level rise, we would expect the populations isolated in
      the three regions to have been homogenized by high dispersal potential. To assess
      these hypotheses, we explore the intraspecific phylogeographical patterns in
      redlip mullet, Chelon haematocheilus. Fragments of 435 bp at the 5' end of
      mitochondrial DNA control region were sequenced for 272 individuals from nine
      localities over most of the species' range. Three distinct lineages were
      detected, which might have diverged in the three marginal seas during Pleistocene
      low sea levels. Contrary to homogenization expectation, there were strong
      differences in the geographical distribution of the three lineages. Analyses of
      molecular variance and the population statistic Phi(ST) also revealed significant
      genetic structure among populations of the three marginal seas. These results
      indicate that gene flow in Chelon haematocheilus is far more restricted spatially
      than predicted by the potential dispersal capabilities of this species. The lack
      of phylogeographical structure in East China Sea may reflect a recent range
      expansion after the last glacial maximum and insufficient time to attain
      migration-drift equilibrium.

PMID- 17217345
TI  - Pleistocene isolation and recent gene flow in Haliotis asinina, an Indo-Pacific
      vetigastropod with limited dispersal capacity.
AB  - Haliotis asinina is a broadcast-spawning mollusc that inhabits Indo-Pacific coral
      reefs. This tropical abalone develops through a nonfeeding larval stage that is
      competent to settle on specific species of coralline algae after 3-4 days in the
      plankton. Failure to contact an inductive algae within 10 days of hatching
      usually results in death. These life cycle characteristics suggest a limited
      capacity for dispersal and thus gene flow. This makes H. asinina particularly
      suitable for elucidating phylogeographical structure throughout the Indo-Malay
      Archipelagoes, and eastern Indian and western Pacific Oceans, all regions of
      biogeographical complexity and high conservation value. We assayed 482 bp of the
      mitochondrial cytochrome oxidase II gene in 206 abalone collected from 16
      geographically discrete sites across the Indian and Pacific Oceans and Indo-Malay
      Archipelagoes. DNA sequence variation was analysed via population genetics and
      phylogenetics, and by nested clade analyses (NCA). Our data resolved clear
      phylogeographical breaks among major biogeographical regions, with sequence
      divergences ranging from a high of 3.7% and 3.0% between Indian and Pacific sites
      and Pacific and Indo-Malay sites, respectively, to a low of 1.1% between Indian
      and Indo-Malay sites. Despite the apparent limited dispersal capacity of H.
      asinina, no finer scale phylogeographical structure was resolved within the
      respective biogeographical regions. However, amova and NCA identified several
      significant associations between haplotypes and geographical distribution, most
      notably higher gene flow among geographical populations associated with major
      ocean currents. Our study provides further evidence that larval dispersal
      capacity alone is not a good predictor of population genetic structure in marine
      invertebrates. We infer instead that a combination of historical events (long
      term barriers followed by range expansion associated with Pleistocene sea level
      changes) and contemporary processes (gene flow restricted by life history and
      oceanography) have shaped observed patterns of H. asinina phylogeography.

PMID- 17217346
TI  - Local-scale genetic structure in the peatmoss Sphagnum fuscum.
AB  - Sphagnum (peatmoss) dominates huge areas of the Northern Hemisphere and acts as a
      significant carbon sink on a global scale, yet little is known about the genetic
      structure of Sphagnum populations. We investigated genetic structure within a
      population of the common peatmoss Sphagnum fuscum, to assess local patterns of
      genetic diversity and the spatial extent of clones. One hundred seventeen shoots
      were sampled from five transects in Fuglmyra, central Norway, and sequenced for
      three anonymous DNA regions. Five neighbourhood patches were marked along each
      transect, and from each patch, five stems were sampled for molecular analyses.
      Seventeen haplotypes could be distinguished and two major groups of haplotypes
      differed by 12 mutational steps. The two major haplotype groups differed
      significantly in microhabitat association along the distance to groundwater table
      and the pH gradients, indicating microhabitat differentiation. The haplotypes
      within these groups were all genetically similar, differing by one or two
      mutations. The most common haplotype occurred in four transects separated by 250
      m distance. Most of the molecular variation in the population was found among
      transects, and within patches. Large dominating clones within each transect
      resulted in low variation explained by the among-patch-within-transect component
      of spatial structure. Mutation appears to account for a larger proportion of the
      population variation than recombination. Within the population, vegetative growth
      and asexual reproduction from gametophyte fragments dominate as the main
      reproductive mode.

PMID- 17217347
TI  - Reproductive strategy, clonal structure and genetic diversity in populations of
      the aquatic macrophyte Sparganium emersum in river systems.
AB  - Many aquatic and riparian plant species are characterized by the ability to
      reproduce both sexually and asexually. Yet, little is known about how spatial
      variation in sexual and asexual reproduction affects the genotypic diversity
      within populations of aquatic and riparian plants. We used six polymorphic
      microsatellites to examine the genetic diversity within and differentiation among
      17 populations (606 individuals) of Sparganium emersum, in two Dutch-German
      rivers. Our study revealed a striking difference between rivers in the mode of
      reproduction (sexual vs. asexual) within S. emersum populations. The mode of
      reproduction was strongly related to locally reigning hydrodynamic conditions.
      Sexually reproducing populations exhibited a greater number of multilocus
      genotypes compared to asexual populations. The regional population structure
      suggested higher levels of gene flow among sexually reproducing populations
      compared to clonal populations. Gene flow was mainly mediated via hydrochoric
      dispersal of generative propagules (seeds), impeding genetic differentiation
      among populations even over river distances up to 50 km. Although evidence for
      hydrochoric dispersal of vegetative propagules (clonal plant fragments) was
      found, this mechanism appeared to be relatively less important. Bayesian-based
      assignment procedures revealed a number of immigrants, originating from outside
      our study area, suggesting intercatchment plant dispersal, possibly the result of
      waterfowl-mediated seed dispersal. This study demonstrates how variation in local
      environmental conditions in river systems, resulting in shifting balances of
      sexual vs. asexual reproduction within populations, will affect the genotypic
      diversity within populations. This study furthermore cautions against
      generalizations about dispersal of riparian plant species in river systems.

PMID- 17217348
TI  - Appraisal of the consequences of the DDT-induced bottleneck on the level and
      geographic distribution of neutral genetic variation in Canadian peregrine
      falcons, Falco peregrinus.
AB  - Peregrine falcon populations underwent devastating declines in the mid-20th
      century due to the bioaccumulation of organochlorine contaminants, becoming
      essentially extirpated east of the Great Plains and significantly reduced
      elsewhere in North America. Extensive re-introduction programs and restrictions
      on pesticide use in Canada and the United States have returned many populations
      to predecline sizes. A proper population genetic appraisal of the consequences of
      this decline requires an appropriate context defined by (i) meaningful
      demographic entities; and (ii) suitable reference populations. Here we explore
      the validity of currently recognized subspecies designations using data from the
      mitochondrial control region and 11 polymorphic microsatellite loci taken from
      184 contemporary individuals from across the breeding range, and compare patterns
      of population genetic structure with historical patterns inferred from 95 museum
      specimens. Of the three North American subspecies, the west coast marine
      subspecies Falco peregrinus pealei is well differentiated genetically in both
      time periods using nuclear loci. In contrast, the partitioning of continental
      Falco peregrinus anatum and arctic Falco peregrinus tundrius subspecies is not
      substantiated, as individuals from these subspecies are historically
      indistinguishable genetically. Bayesian clustering analyses demonstrate that
      contemporary genetic differentiation between these two subspecies is mainly due
      to changes within F. p. anatum (specifically the southern F. p. anatum
      populations). Despite expectations and a variety of tests, no genetic bottleneck
      signature is found in the identified populations; in fact, many contemporary
      indices of diversity are higher than historical values. These results are
      rationalized by the promptness of the recovery and the possible introduction of
      new genetic material.

PMID- 17217349
TI  - Genetic structure and reproductive strategy of the ant Cardiocondyla elegans:
      strictly monogynous nests invaded by unrelated sexuals.
AB  - Cardiocondyla elegans is a Mediterranean ant that nests on river banks. It rears
      only wingless (ergatoid) males that live peacefully in the same nest as opposed
      to other species of the same genus, which have both peaceful, winged and mutually
      aggressive 'ergatoid' males. Using microsatellite analysis, we investigated the
      genetic structure of 21 colonies from three different locations as well as the
      parentage of sexuals of two colonies of C. elegans. We show that C. elegans is
      strictly monogynous, and that its nests can contain foreign sexuals. The presence
      of alien sexuals inside ant nests is described for the first time and probably
      counteracts inbreeding resulting from matings between siblings. In the
      laboratory, aggression tests showed that workers only allow alien males to enter
      their nests, while all winged female sexuals attempting to enter were attacked.
      Nevertheless, the presence of alien female sexuals in nests in the field seems to
      result from active carrying behaviour by workers during the reproductive period.

PMID- 17217350
TI  - Cryptic speciation in two widespread subterranean amphipod genera reflects
      historical drainage patterns in an ancient landscape.
AB  - The landscape of the Pilbara region of Western Australia has been relatively
      unchanged for 100 million years. The ancient river systems of this region might
      be expected to be sources of isolation and divergence for aquatic species. Hence,
      the occurrence of widespread groundwater taxa in this landscape offers the
      opportunity to examine associations between genetic diversity and drainage
      patterns. Pilbarus and Chydaekata are two widespread genera of subterranean
      amphipods endemic to the Pilbara, each occupying multiple tributaries. We used
      molecular data to examine the roles of drainage patterns in structuring genetic
      diversity. Gene flow within a tributary may be facilitated by the occasional
      occurrence of these amphipods in springs, which results in their downstream
      dispersal during episodic flooding. However, tributary boundaries may form
      hydrological barriers to gene flow, resulting in localised isolation of
      populations and divergence. Samples of both genera, collected throughout three
      river basins, were examined for sequence divergence in the cytochrome c oxidase I
      mitochondrial gene. There was no evidence of contemporary gene flow among
      populations of either genus, and each tributary contained highly divergent
      lineages, which were not associated with similar morphological differentiation.
      This suggests cryptic speciation has occurred, and similar phylogenetic signals
      in both taxa imply similar evolutionary histories. Surface populations may have
      been driven into subterranean refugia by the cessation of flow in the rivers,
      associated with Tertiary climate change, while morphological evolution may have
      been constrained by stabilising selection. The lack of congruence between
      molecular diversity and morphology raises important practical issues for
      conservation.

PMID- 17217351
TI  - Characterization and distribution of Pogonomyrmex harvester ant lineages with
      genetic caste determination.
AB  - Genetic caste determination has been described in two populations of Pogonomyrmex
      harvester ants, each comprising a pair of interbreeding lineages. Queens mate
      with males of their own and of the alternate lineage and produce two types of
      diploid offspring, those fertilized by males of the queens' lineage which develop
      into queens and those fertilized by males of the other lineage which develop into
      workers. Each of the lineages has been shown to be itself of hybrid origin
      between the species Pogonomyrmex barbatus and Pogonomyrmex rugosus, which both
      have typical, environmentally determined caste differentiation. In a large scale
      genetic survey across 35 sites in Arizona, New Mexico and Texas, we found that
      genetic caste determination associated with pairs of interbreeding lineages
      occurred frequently (in 26 out of the 35 sites). Overall, we identified eight
      lineages with genetic caste determination that always co-occurred in the same
      complementary lineage pairs. Three of the four lineage pairs appear to have a
      common origin while their relationship with the fourth remains unclear. The level
      of genetic differentiation among these eight lineages was significantly higher
      than the differentiation between P. rugosus and P. barbatus, which questions the
      appropriate taxonomic status of these genetic lineages. In addition to being
      genetically isolated from one another, all lineages with genetic caste
      determination were genetically distinct from P. rugosus and P. barbatus, even
      when colonies of interbreeding lineages co-occurred with colonies of either
      putative parent at the same site. Such nearly complete reproductive isolation
      between the lineages and the species with environmental caste determination might
      prevent the genetic caste determination system to be swept away by gene flow.

PMID- 17217352
TI  - Hybridization among cryptic species of the cellar fungus Coniophora puteana
      (Basidiomycota).
AB  - In this study we have analysed the genetic variation and phylogeography in a
      global sample of the cellar fungus Coniophora puteana, which is an important
      destroyer of wooden materials indoor. Multilocus genealogies of three DNA regions
      (beta tubulin, nrDNA ITS and translation elongation factor 1alpha) revealed the
      occurrence of three cryptic species (PS1-3) in the morphotaxon C. puteana. One of
      the lineages (PS3) is apparently restricted to North America while the other two
      (PS1-2) have wider distributions on multiple continents. Interspecific
      hybridization has happened between two of the lineages (PS1 and PS3) in North
      America. In three dikaryotic isolates, two highly divergent beta tubulin alleles
      coexisted, one derived from PS1 and one from PS3. Furthermore, one isolate
      included a recombinant ITS sequence, where ITS1 resembled the ITS1 version of PS3
      while ITS2 was identical to a frequent PS1 ITS2 version. This pattern must be due
      to hybridization succeeded by intralocus recombination in ITS. The results
      further indicated that introgression has happened between subgroups appearing in
      PS1. We hypothesize that the observed reticulate evolution is due to previous
      allopatric separation followed by more recent reoccurrence in sympatry, where
      barriers to gene flow have not yet evolved. A complex phylogeographical structure
      is observed in the morphotaxon C. puteana caused by (i) cryptic speciation; (ii)
      the interplay between natural migration and distribution patterns and probably
      more recent human mediated dispersal events; and (iii) hybridization and
      introgression.

PMID- 17217353
TI  - Mitogenetic structure of brown bears (Ursus arctos L.) in northeastern Europe and
      a new time frame for the formation of European brown bear lineages.
AB  - We estimated the phylogenetic relationships of brown bear maternal haplotypes
      from countries of northeastern Europe (Estonia, Finland and European Russia),
      using sequences of mitochondrial DNA (mtDNA) control region of 231 bears. Twenty
      five mtDNA haplotypes were identified. The brown bear population in northeastern
      Europe can be divided into three haplogroups: one with bears from all three
      countries, one with bears from Finland and Russia, and the third composed almost
      exclusively of bears from European Russia. Four haplotypes from Finland and
      European Russia matched exactly with haplotypes from Slovakia, suggesting the
      significance of the current territory of Slovakia in ancient demographic
      processes of brown bears. Based on the results of this study and those from the
      recent literature, we hypothesize that the West Carpathian Mountains have served
      either as one of the northernmost refuge areas or as an important movement
      corridor for brown bears of the Eastern lineage towards northern Europe during or
      after the last ice age. Bayesian analyses were performed to investigate the
      temporal framework of brown bear lineages in Europe. The molecular clock was
      calibrated using Beringian brown bear sequences derived from radiocarbon-dated
      ancient samples, and the estimated mutation rate was 29.8% (13.3%-47.6%) per
      million years. The whole European population and Western and Eastern lineages
      formed about 175,000, 70,000 and 25,000 years before present, respectively. Our
      approach to estimating the time frame of brown bear evolution demonstrates the
      importance of using an appropriate mutation rate, and this has implications for
      other studies of Pleistocene populations.

PMID- 17217354
TI  - Phylogeographic concordance in the southeastern United States: the flatwoods
      salamander, Ambystoma cingulatum, as a test case.
AB  - Well-supported, congruent phylogeographic and biogeographic patterns permit the
      development of a priori phylogeographic and distributional predictions. In the
      southeastern Coastal Plain of the United States, the common discovery of east
      west disjunctions (phylogeographic breaks and species' distributional boundaries)
      suggests that similar disjunctions should occur in codistributed taxa. Despite
      the near ubiquity of these disjunctions, the most recent morphological analyses
      of the flatwoods salamander, Ambystoma cingulatum, indicate that none occur in
      this low-vagility, Coastal Plain endemic. We conducted molecular and
      morphological analyses to test whether the flatwoods salamander is an exception
      to this common biogeographic pattern. Assessing geographic variation in this
      species is also an important management tool for this threatened, declining
      amphibian. We demonstrate that flatwoods salamanders, as predicted by comparisons
      to codistributed taxa, are polytypic with a major disjunction at the Apalachicola
      River. This drainage is a common site for east-west phylogeographic breaks,
      probably because repeated marine embayments during the Pliocene and Pleistocene
      interglacials generated barriers to gene flow. Based on mitochondrial DNA,
      morphology, and allozymes, we recognize two species of flatwoods salamanders --
      Ambystoma cingulatum to the east of the Apalachicola drainage and Ambystoma
      bishopi to the west. Given this increased diversity, the conservation status of
      these two taxa may warrant re-evaluation. More generally, these results emphasize
      that in the absence of taxon-specific data, established comparative patterns can
      provide strong expectations for designing management units for unstudied species
      of conservation concern.

PMID- 17217355
TI  - Clonal diversity of the marine trematode Maritrema novaezealandensis within
      intermediate hosts: the molecular ecology of parasite life cycles.
AB  - We quantified the clonal diversity of the New Zealand marine trematode Maritrema
      novaezealandensis (n = 1250) within Zeacumantus subcarinatus snail (n = 25) and
      Macrophthalmus hirtipes crab (n = 25) intermediate hosts using four to six
      microsatellite loci, and investigated the potential biological and physical
      factors responsible for the observed genetic patterns. Individual snails
      harboured one to five trematode genotypes and 48% of snails were infected by
      multiple parasite genotypes. Overall, the number of parasite genotypes did not
      increase with snail size, but was highest in intermediate-sized snails.
      Significantly larger numbers of parasite genotypes were detected in crabs
      (relative to snails; P < 0.001), with 16-25 genotypes recovered from individual
      crabs. Although crabs are typically infected by small numbers of cercariae
      sourced from many snails, they are occasionally infected by large numbers of
      cercariae sourced from single snails. The latter cases explain the significant
      genetic differentiation of trematode populations detected among their crab hosts
      (F(ST) = 0.009, P < 0.001). Our results suggest that the timing of infection
      and/or intraspecific competition among parasite clones within snails determine(s)
      the diversity of parasite clones that snails harbour. The presence of a large
      number of infected snails and tidal mixing of cercariae prior to infection
      results in crabs potentially harbouring hundreds of parasite genotypes despite
      the crabs' territorial behaviour.

PMID- 17217356
TI  - Insertion polymorphism of transposable elements and population structure of
      Anopheles gambiae M and S molecular forms in Cameroon.
AB  - The insertion polymorphism of five transposable element (TE) families was studied
      by Southern blots in several populations of the M and S molecular forms of the
      mosquito Anopheles gambiae sensu stricto from southern Cameroon. We showed that
      the mean TE insertion site number and the within-population insertion site
      polymorphism globally differed between the M and S molecular forms. The
      comparison of the TE insertion profiles of the populations revealed a significant
      differentiation between these two molecular forms (0.163 < Phi(ST) < 0.371). We
      cloned several insertions of a non-LTR retrotransposon (Aara8) that were fixed in
      one form and absent in the other one. The only insertion that could be clearly
      located on a chromosome arm mapped to cytological division 6 of chromosome X,
      confirming the importance of this region in the ongoing speciation between the M
      and S molecular forms.

PMID- 17217357
TI  - Gene, phenotype and function: GLABROUS1 and resistance to herbivory in natural
      populations of Arabidopsis lyrata.
AB  - The molecular genetic basis of adaptive variation is of fundamental importance
      for evolutionary dynamics, but is still poorly known. Only in very few cases has
      the relationship between genetic variation at the molecular level, phenotype and
      function been established in natural populations. We examined the functional
      significance and genetic basis of a polymorphism in production of leaf hairs,
      trichomes, in the perennial herb Arabidopsis lyrata. Earlier studies suggested
      that trichome production is subject to divergent selection. Here we show that the
      production of trichomes is correlated with reduced damage from insect herbivores
      in natural populations, and using statistical methods developed for medical
      genetics we document an association between loss of trichome production and
      mutations in the regulatory gene GLABROUS1. Sequence data suggest that
      independent mutations in this regulatory gene have provided the basis for
      parallel evolution of reduced resistance to insect herbivores in different
      populations of A. lyrata and in the closely related Arabidopsis thaliana. The
      results show that candidate genes identified in model organisms provide a
      valuable starting point for analysis of the genetic basis of phenotypic variation
      in natural populations.

PMID- 17217358
TI  - Increased blood loss in upright birthing positions originates from perineal
      damage.
AB  - OBJECTIVE: To assess whether the risk of severe blood loss is increased in semi
      sitting and sitting position, and if so, to which extent blood loss from perineal
      damage is responsible for this finding. DESIGN: Secondary analysis of data from a
      large trial. SETTING: Primary care midwifery practices in the Netherlands.
      POPULATION: About 1646 low-risk women who had a spontaneous vaginal delivery.
      METHODS: Blood loss was measured using a weighing scale and measuring jug.
      Logistic regression analysis was used to examine the net effects of birthing
      position and perineal damage on blood loss greater than 500 ml. MAIN OUTCOME
      MEASURES: Mean total blood loss and incidence of blood loss greater than 500 ml
      and 1000 ml. RESULTS: Mean total blood loss and the incidence of blood loss
      greater than 500 ml and 1000 ml were increased in semi-sitting and sitting
      position. In logistic regression analysis, the interaction between birthing
      position and perineal damage was almost significantly associated with an
      increased risk of blood loss greater than 500 ml. Semi-sitting and sitting
      position were only significant risk factors among women with perineal damage (OR
      1.30, 95% CI 1.00-1.69 and OR 2.25, 95% CI 1.37-3.71, respectively). Among women
      with intact perineum, no association was found. CONCLUSIONS: Semi-sitting and
      sitting birthing positions only lead to increased blood loss among women with
      perineal damage.

PMID- 17217359
TI  - Are two doses of misoprostol after mifepristone for early abortion better than
      one?
AB  - OBJECTIVE: The objective of this study was to determine if a repeat dose of
      misoprostol following mifepristone or a single dose of misoprostol increases the
      efficacy of medical termination of pregnancy. DESIGN: Randomised, placebo
      controlled trial. SETTING: K.E.M. Hospital, Pune, India, and the Health Centre,
      Larsen and Toubro Limited, Mumbai, India. SAMPLE: A total of 300 women seeking an
      abortion with amenorrhoea of 8 weeks or less. Methods Women were randomised to
      receive one or two doses of 400 microgram oral misoprostol at the clinic 48 hours
      after administration of 200 mg mifepristone. Main outcome measure Complete
      abortion without surgical intervention. Results The repeat administration of
      misoprostol 400 microgram improved the complete abortion rate from 86 to 92% and
      significantly reduced the rate of continuing pregnancy from 7 to 1%. Almost all
      the women who were administered the additional dose of misoprostol were either
      very satisfied (58%) or satisfied (37%) with the method. Conclusion While an
      additional oral dose of 400 microgram misoprostol did not significantly increase
      the rate of complete abortion without surgical intervention, the additional dose
      did significantly reduce the rate of continuing pregnancies without compromising
      the acceptability and ease of use of the method.

PMID- 17217360
TI  - Evaluation of a decision aid for women with breech presentation at term: a
      randomised controlled trial [ISRCTN14570598].
AB  - OBJECTIVES: To evaluate the effectiveness of a decision aid for women with a
      breech presentation compared with usual care. DESIGN: Randomised controlled
      trial. SETTING: Tertiary obstetric hospitals offering external cephalic version
      (ECV). POPULATION: Women with a singleton pregnancy were diagnosed antenatally
      with a breech presentation at term, and were clinically eligible for ECV.
      METHODS: Women were randomised to either receive a decision aid about the
      management options for breech presentation in addition to usual care or to
      receive usual care only with standard counselling from their usual pregnancy care
      provider. The decision aid comprised a 24-page booklet supplemented by a 30
      minute audio-CD and worksheet that was designed for women to take home and review
      with a partner. MAIN OUTCOME MEASURES: Decisional conflict (uncertainty),
      knowledge, anxiety and satisfaction with decision making, and were assessed using
      self-administered questionnaires. RESULTS: Compared with usual care, women
      reviewing the decision aid experienced significantly lower decisional conflict
      (mean difference -8.92; 95% CI -13.18, -4.66) and increased knowledge (mean
      difference 8.40; 95% CI 3.10, 13.71), were more likely to feel that they had
      enough information to make a decision (RR 1.30; 95% CI 1.14, 1.47), had no
      increase in anxiety and reported greater satisfaction with decision making and
      overall experience of pregnancy and childbirth. In contrast, 19% of women in the
      usual care group reported they would have made a different decision about their
      care. CONCLUSIONS: A decision aid is an effective and acceptable tool for
      pregnant women that provides an important adjunct to standard counselling for the
      management of breech presentation.

PMID- 17217361
TI  - The Hayman technique: a simple method to treat postpartum haemorrhage.
AB  - Of the several uterine compression sutures described in more recent years to
      treat postpartum haemorrhage (PPH), the Hayman suture offers the potential
      advantages that can be applied faster and easier, avoiding the performance of a
      lower segment hysterotomy when PPH follows a vaginal delivery. Data on efficacy
      and safety are limited, and long-term follow-up information are lacking. We
      report our experience with the Hayman suture in 11 consecutive women with massive
      PPH. Of these, ten were successfully treated without further interventions. One
      woman ultimately required a hysterectomy. Postoperative course was uncomplicated
      in all the cases. The median follow-up time was 11 months (range 1-19). One woman
      conceived spontaneously 10 months after the procedure. Our results suggest that
      the Hayman suture is an effective and safe treatment for PPH.

PMID- 17217363
TI  - Inflammation, cancer and chemoresistance: taking advantage of the toll-like
      receptor signaling pathway.
AB  - The association between chronic inflammation and cancer has long been observed.
      Furthermore, NF-kappaB activation and the subsequent production of cytokines,
      chemokines, growth factors, and antiapoptotic proteins has been found to be
      involved in cancer progression and chemoresistance. However, the signals inducing
      NF-kappaB in cancer cells are still not well understood. Here, we reviewed the
      association between chronic inflammation and cancer, the role of NF-kappaB and
      its inhibitors as potential anticancer drugs, and Toll-like receptors as possible
      signal initiators for NF-kappaB activation and inflammation-induced
      carcinogenesis and chemoresistance. Furthermore, we propose that, the stimulation
      of Toll-like receptors by microbial components and/or endogenous ligands may
      represent the initial signal promoting a proinflammatory environment that will
      enhance tumor growth and chemoresistance.

PMID- 17217362
TI  - Effects of an antiatherogenic diet during pregnancy on markers of maternal and
      fetal endothelial activation and inflammation: the CARRDIP study.
AB  - OBJECTIVE: To study the effect of an antiatherogenic diet on maternal and cord
      blood concentrations of systemic biomarkers of endothelial cell activation,
      haemostasis and inflammation. DESIGN: Single blinded randomised controlled
      clinical trial. SETTING: Obstetric outpatient clinic and maternity unit of a
      university hospital in Norway. POPULATION: Nonsmoking pregnant women aged 21-38
      years carrying a single fetus and with no previous pregnancy-related
      complications. METHODS: Subjects (n = 290) were randomised to continue their
      usual diet or to adopt a diet low in saturated fat and cholesterol from
      gestational week 17-20 to birth. Soluble forms of cellular adhesion molecules,
      high-sensitivity C-reactive protein (CRP) and haemostatic markers were measured
      at 17-20 weeks of gestation (baseline) and subsequently up to week 36. All the
      above, except CRP, were also measured in cord blood. MAIN OUTCOME MEASURES:
      Concentrations of maternal and fetal biomarkers and maternal CRP. RESULTS: All
      biomarkers except CRP levels increased significantly during the study period in
      both the intervention and control groups. None of the maternal or fetal
      biomarkers were influenced by the intervention (P > 0.05) except for a tendency
      to lower concentrations of cord blood tissue plasminogen activator antigen in the
      intervention group compared with the control group, median (interquartile range)
      5.4 ng/ml (3.1-7.7) versus 5.8 ng/ml (3.5-11.8), P = 0.05. CONCLUSION: An
      antiatherogenic diet in pregnancy did not significantly influence maternal or
      fetal blood concentrations of a range of biomarkers for inflammation. Thus, the
      previously reported effects of a cholesterol-lowering diet on maternal lipid
      profile and preterm delivery (<37 complete weeks of gestation) do not seem to
      involve changes in the systemic inflammatory responses of pregnancy.

PMID- 17217364
TI  - NK cell function in the human female reproductive tract.
AB  - PROBLEM: Uterine NK cells have a unique phenotype compared with blood NK cell
      subsets, yet little is known about how NK cells function as a part of the innate
      immune cell network in the female reproductive tract. METHOD OF STUDY: The
      expression of key receptors and function of uterine NK cells in response to
      cytokines, sex hormones, and pathogen associated molecular patterns (PAMPs) was
      analyzed. This article summarizes recent findings on the biology and function of
      NK cells in the female reproductive tract. RESULTS: Uterine NK cells express Toll
      like receptors and respond to cytokines and PAMPs under specific conditions.
      Evidence indicates that NK cells play an important role in the reorganization of
      blood vessels during pregnancy. CONCLUSIONS: Human uterine NK cells are a major
      population of leukocytes in the endometrium and play an important role as a
      component of host defense and in successful reproduction.

PMID- 17217365
TI  - Effect of experimental genital mycoplasmosis on production of matrix
      metalloproteinases in membranes and amniotic fluid of Sprague-Dawley rats.
AB  - PROBLEM: Preterm, premature rupture of membranes (PPROM) is a dire pregnancy
      outcome that is frequently associated with infection by the genital mycoplasmas,
      Mycoplasma hominis, Ureaplasma parvum, and U. urealyticum. One potential
      mechanism by which these microorganisms may cause PPROM is by increasing the
      concentration of matrix metalloproteinases (MMPs) in the membranes and amniotic
      fluid. We tested this hypothesis in a well-defined model system of genital
      infection with M. pulmonis, a natural reproductive pathogen of rats. METHOD OF
      STUDY: Timed-pregnant, specific pathogen-free, Sprague-Dawley rats were infected
      with 10(7) CFU M. pulmonis at gestation day (gd) 14. Controls received an
      equivalent volume (100 microL) of sterile medium. At gd 18, rats were euthanized,
      and membranes and amniotic fluids were harvested and stored at -70 degrees C
      until analysis. Proteinase activity of amniotic fluid and membranes was resolved
      on discontinuous 7.5% sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      gelatin zymography gels. Band intensity was determined using a digital gel
      documentation system and the manufacturer's software (Kodak). RESULTS:
      Gelatinolytic activity associated with a band similar in molecular weight to
      ProMMP-9 (92 kDa, the inactive precursor of MMP-9) was significantly increased in
      amniotic fluids and membranes harvested from M. pulmonis-treated pups at gd 18
      when compared with tissues harvested from control pups. Both ProMMP-9 and ProMMP
      2 (72 kDa, the inactive precursor of MMP-2) were increased in infected animals at
      gd 21. CONCLUSION: Our study suggests that the genital mycoplasmas can increase
      MMP-9 production in vivo.

PMID- 17217366
TI  - Granulated and non-granulated decidual prolactin-related protein-positive
      decidual cells in the pregnant mouse endometrium.
AB  - PROBLEM: Identification of the cell types responsible for the synthesis of
      decidual prolactin-related protein (dPRP) in the pregnant mouse endometrium.
      METHOD OF STUDY: Histochemistry and immunocytochemistry were used to determine
      peri-implantation dPRP and perlecan distribution in the mouse uterus. RESULTS: We
      identified dPRP in pre-decidual and mature decidual cells from days 5 to 12 of
      pregnancy. On day 8, dPRP immunoreactivity was detected within cytoplasmic
      granules of a specific population of granulated decidual cells (GDCs). In
      mesometrial decidual cells, weak immunoreactivity was seen from days 7 to 14.
      Between days 11 and 14, dPRP was found in cytoplasm and in the extracellular
      matrix surrounding islands of spongiotrophoblast. Perlecan, a heparan sulfate
      proteoglycan, was co-localized with dPRP. CONCLUSION: GDCs are a putative source
      of dPRP in pregnant mice. Co-localization of perlecan with dPRP suggests that the
      former acts as a dPRP reservoir and facilitates its paracrine effect in
      developing placental tissues.

PMID- 17217367
TI  - Combined thrombophilic mutations in women with unexplained recurrent miscarriage.
AB  - PROBLEM: To compare the prevalence of five common thrombophilic polymorphisms and
      their combination in women with recurrent miscarriage and a control group. METHOD
      OF STUDY: Genomic analysis using polymerase chain reaction (PCR) was carried out
      in patients with two or more miscarriages and controls for Factor V Leiden,
      Factor V A1299H (HR2), Factor II G20210A, MTHFR C677T and MTHFR A1298C. Secondary
      analyses were made for number of miscarriages and gestational age at miscarriage.
      RESULTS: None the mutations was associated with significantly increased risk for
      recurrent miscarriage. The prevalence of combined thrombophilias (4/88 versus
      2/88) did not increase the risk for miscarriage (OR 2.04, 95% CI 0.36-11.47).
      Although virtually all patients with thrombophilia had miscarriages<or=10 weeks,
      statistical significance was not reached due to the small size of the >10 weeks'
      subgroup. There was no difference in the distribution of Factor V Leiden
      (P=1.000), FII G20210A (P=0.652), and MTHFR C677T (P=0.869) between patients with
      two and three or more miscarriages, whereas MTHFR A1298C was more common among
      patients with two miscarriages (P=0.017). CONCLUSIONS: Combinations of the five
      thrombophilic mutations studied are an uncommon event with heterogeneous pattern
      and they do not significantly increase the risk for miscarriage.

PMID- 17217368
TI  - Relationship between level of serum sperm immobilizing antibody and its
      inhibitory effect on sperm migration through cervical mucus in immunologically
      infertile women.
AB  - PROBLEM: Sperm immobilizing antibodies often interfere with the penetration of
      sperm through the cervical mucus. However, the relationship between sperm
      immobilizing antibody titer and the result of the post-coital test (PCT) has not
      yet been clarified. The aim of this study was to investigate whether the 50%
      sperm immobilization unit (SI50) titer, a quantitative measure of sperm
      immobilizing antibody, in patients' sera was correlated with the result of PCT.
      METHOD OF STUDY: The sperm immobilization test (SIT) was performed for 2834
      infertile women in two university hospitals. The SI50 titers were evaluated by
      quantitative SIT. In some cases with sperm immobilizing antibody, PCT was carried
      out before ovulation and assessed according to the criteria of World Health
      Organization (1992). Infertile couples with abnormal semen characteristics were
      excluded. RESULTS: Seventy-four of 2834 women had sperm immobilizing antibodies
      in their sera, giving a positive rate of 2.6%. Twenty-four (77.4%) of 31 women
      with sperm immobilizing antibodies and 28 (20.4%) of 137 women without the
      antibody had abnormal PCT results. There was a significant difference between the
      two groups (P<0.0001). When patients with sperm immobilizing antibodies were
      divided into two groups according to the SI50 titers, the abnormal result of PCT
      was obtained in all 10 patients with high (>10) SI50 titers, while that was 14
      (66.7%) in 21 patients with low (10) SI50 titers. There was a significant
      difference between the two groups (P=0.04). CONCLUSION: The SI50 titer in the
      serum can predict inhibitory effects on sperm migration through cervical mucus in
      immunologically infertile women. Evaluation of the SI50 titers in patients' sera
      seems to be useful for decision-making in infertile women with sperm immobilizing
      antibodies regarding whether they have the possibility of conceiving by timed
      intercourse.

PMID- 17217369
TI  - Implication of RANTES in the modulation of alloimmune response by progesterone
      during pregnancy.
AB  - PROBLEM: Several studies indicate that RANTES (regulated on activation, normal T
      cell expressed and secreted) is able to downregulate T-cell responses which
      suggest it might be relevant for fetal tolerance induction. However, the role of
      RANTES in pregnancy had not been established. Here we investigate RANTES
      regulation during early pregnancy and potential failures leading to losses of
      pregnancies. METHOD OF STUDY: RANTES and progesterone levels were determined in
      sera and feto-placental units from high resorption rate CBA/JxDBA/2 pregnant
      females and compared with CBA/JxBALB/c normal pregnant mice. RANTES in vitro
      modulation was also studied in nulliparous, primiparous and multiparous CBA/J and
      BALB/c cells in response to paternal alloantigen and progesterone stimulation.
      RESULTS: Nulliparous CBA/J females were quantitatively deficient in RANTES sera
      levels, whereas pregnancies with male BALB/c or DBA/2 increased its production.
      However, feto-placental units from CBA/J females are high producers of
      progesterone and RANTES. CONCLUSION: These data suggest that the beneficial
      effect of RANTES on feto-maternal interface requires an optimal concentration
      range and might be modulated by progesterone, hence exacerbated placental
      expression could be associated with high resorption rate.

PMID- 17217370
TI  - Local markers for prediction of women at higher risk of developing sequelae to
      Chlamydia trachomatis infection.
AB  - PROBLEM: Chlamydial infections are often associated with various fertility
      related disorders. Serological prediction of these has limitations, as they do
      not differentiate between past and current infections. Thus, we looked for local
      markers that could predict more precisely women at higher risk of developing
      severe complications. METHOD OF STUDY: A total of 320 Chlamydia trachomatis
      positive women with or without fertility disorders were tested for the prevalence
      of immunoglobulin A antibodies to synthetic peptides of chlamydial heat-shock
      protein 60 (cHSP60) and cHSP10 along with cervical interferon-gamma (IFN-gamma)
      and serum C-reactive protein (CRP) levels. RESULTS: Positive IFN-gamma level was
      the single best predictor for fertility disorder [odds ratio (OR) 15.4]. The
      predictive value of IFN-gamma could be significantly improved only by the
      addition of CRP test (OR 37.9). CONCLUSION: Positive IFN-gamma levels in cervical
      washes along with elevated CRP levels could be used to predict women who are at
      higher risk of developing fertility disorders.

PMID- 17217371
TI  - Recurrent pregnancy loss and inappropriate local immune response to sex hormones.
AB  - PROBLEM: The cause of recurrent miscarriage is often unknown. Recurrent
      miscarriage may be associated with inappropriate responses to progesterone and
      estrogen. We examined whether the condition may be diagnosed by skin testing.
      METHOD OF STUDY: In a longitudinal prospective study, the weal and flare reaction
      after intradermal injection of estradiol and progesterone was compared in 29
      women with recurrent miscarriage to the response in 10 healthy women. Reactions
      were evaluated after 20 min, 24, and 48 hr and 5 days later. RESULTS: Estrogen
      hypersensitivity was found in 23 patients, and progesterone hypersensitivity in
      20 patients. No patient in the control group demonstrated sex hormone
      hypersensitivity. CONCLUSION: Recurrent pregnancy loss may be associated with
      inappropriate local immune responses to sex hormones. Further research is
      necessary into the mechanisms of hypersensitivity to estrogen and progesterone
      and their interactions with other systems.

PMID- 17217372
TI  - The metabolic syndrome: definition, pathogenesis and therapy.

PMID- 17217373
TI  - CETP inhibition in cardiovascular risk management: a critical appraisal.
AB  - In view of the cardioprotective effect of high-density lipoproteins (HDL) and the
      limited effects of statin and fibrate therapy on HDL cholesterol, it is
      clinically relevant to test whether pharmacological treatment aimed at raising
      HDL lowers cardiovascular risk. Cholesteryl ester transfer protein (CETP) is a
      new therapeutic target, because the cholesteryl ester transfer process lowers HDL
      cholesterol and contributes to an atherogenic lipoprotein profile, particularly
      when plasma triglycerides are high. Clinical evidence suggests that coronary
      artery calcification as well as intima media thickness is positively related to
      plasma cholesteryl ester transfer, and that high plasma CETP concentration is
      associated with increased cardiovascular risk in hypertriglyceridaemia. However,
      CETP could also have anti-atherogenic potential, since it provides a potentially
      beneficial route for delivery of HDL-derived cholesteryl esters to the liver. In
      addition, CETP could also favourably stimulate peripheral cell cholesterol
      removal and enhance hepatic cholesterol uptake. Recent evidence suggests that a
      high CETP level may confer lower cardiovascular risk in the context of low
      triglycerides. At maximal doses, the CETP inhibitors JTT-705 and torcetrapib
      elicit a marked rise in HDL cholesterol of up to 34% and 91-106%, respectively.
      The effectiveness of these drugs on (intermediate) clinical outcome measures is
      currently being tested in large-scale phase III clinical trials, with torcetrapib
      being only evaluated in combination therapy with atorvastatin. When and how to
      use CETP inhibitors, e.g. in combination with a statin or a fibrate, is a major
      challenge. We propose that low HDL cholesterol in the context of high
      triglycerides, such as found in type 2 diabetes mellitus, could become an
      important indication area for this new class of drugs.

PMID- 17217374
TI  - Is arterial stiffening in Alstrom syndrome linked to the development of
      cardiomyopathy?
AB  - BACKGROUND: Alstrom syndrome (AS) is a rare autosomal recessive condition
      characterized by retinal degeneration, childhood obesity, and severe insulin
      resistance. Dilated cardiomyopathy of unknown aetiology is a well-recognized and
      potentially lethal complication. The aim of this study was to investigate the
      relationship between vascular function, hyperinsulinaemia and cardiac performance
      in AS. MATERIALS AND METHODS: Fifteen subjects with AS (mean age 21 years, range
      10-35) were studied and compared with age-, sex-, and blood pressure-matched
      healthy controls. Large artery stiffness and wave reflections were assessed in
      both groups by measuring aortic and brachial pulse wave velocity (PWV) (carotid
      femoral and carotid-radial) and augmentation index (AIX) (Sphygmocor). In AS
      subjects, left ventricular function was assessed by echocardiography and
      metabolic parameters including fasting insulin, glucose, lipids and brain
      natriuretic peptide were also measured. RESULTS: Comparing AS subjects vs.
      controls (mean +/- SD), AIX was elevated in AS subjects (18 +/- 9% vs. 3 +/- 11%,
      P < 0.0001). No significant changes in brachial PWV (8.1 +/- 1.3 m s(-1) vs. 7.3
      +/- 1.1 m s(-1), P = 0.14) or aortic PWV (6.5 +/- 1.1 m s(-1) vs. 6.0 +/- 1.0 m
      s(-1), P = 0.26) were observed. AS subjects were hyperinsulinaemic and had
      disturbances in lipid profiles relative to controls. No correlations were
      observed between vascular, metabolic and echocardiographic parameters.
      CONCLUSIONS: In AS there are alterations in the shape of the central arterial
      pressure waveform associated with augmented aortic systolic pressure and
      indicative of increased wave reflection. Unfavourable central arterial
      haemodynamics in AS may contribute to the development of cardiomyopathy but other
      aetiological factors are probably involved.

PMID- 17217375
TI  - Robust association of the APOE epsilon4 allele with premature myocardial
      infarction especially in patients without hypercholesterolaemia: the Aachen
      study.
AB  - BACKGROUND: Genetic influence on the manifestation of coronary artery disease
      (CAD) and myocardial infarction (MI) has been shown previously. From many
      candidate genes the APOE (apolipoprotein E) with the major alleles
      epsilon2/epsilon3/epsilon4 is in the focus of interest. MATERIALS AND METHODS: In
      1817 patients admitted for their first left heart catheterization at a premature
      age (males < 55 and females < 65) the association of APOE alleles with MI was
      analysed. Genotyping was done by 5' exonuclease assay (TaqMan). RESULTS APOE was
      significantly associated with hypercholesterolaemia (epsilon4 72% vs. epsilon3
      66% vs. epsilon2 51%; P < 0.0001), and premature MI (epsilon4 57% vs. epsilon3
      50% vs. epsilon2 41%; P < 0.0001; hazard ratio 1.41, 95%CI 1.14-1.75). In
      patients without hypercholesterolaemia, the APOE allele epsilon4 was highly
      predictive for the presence of premature MI (epsilon4 55% vs. epsilon3 45% vs.
      epsilon2 28%; P < 0.0001; hazard ratio 1.75, 95%CI 1.19-2.57). CONCLUSION: The
      APOEepsilon4 allele shows a robust association with premature MI independent of
      hypercholesterolaemia.

PMID- 17217376
TI  - Comparison of different definitions of the metabolic syndrome.
AB  - BACKGROUND: The International Diabetes Federation (IDF) published a new
      definition of the metabolic syndrome (MetS). For this definition we compared
      frequency, concordance, clinical and laboratory stigmata and carotid
      atherosclerosis with those of the established definitions by the National
      Cholesterol Education Program (NCEP) and World Health Organization (WHO).
      MATERIALS AND METHODS: A total of 1518 subjects (943 men, 575 women) from the
      Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk
      (SAPHIR), free of clinical atherosclerosis, were included in this study. To
      estimate insulin sensitivity two methods, i.e. homeostasis model assessment of
      insulin resistance (HOMA-IR) and the short insulin tolerance test, were employed.
      Carotid intima media thickness (IMT) and plaque extent were quantified for all
      subjects using high-resolution ultrasound. RESULTS: Prevalence of the MetS was
      18.7% for men and 16.2% for women for the WHO definition, 18.9% and 17.0%,
      respectively, for the NCEP definition, and 25.8% and 19.5%, respectively, for the
      IDF definition. Concordance was lower between the definitions of WHO and IDF (<
      50%) than between NCEP and IDF (> 67%). Compared to subjects identified by NCEP
      definition, subjects identified in excess by IDF (3.1-11.7%) showed less insulin
      resistance and lower IMT and plaque extent indistinguishable from MetS-free
      subjects. CONCLUSIONS: Our data suggest that the IDF definition includes subjects
      as MetS sufferers above these detected by NCEP or WHO, who exhibit considerably
      less insulin resistance and carotid atherosclerosis blurring the distinction
      between health and disease.

PMID- 17217377
TI  - Helicobacter pylori-induced apoptosis in T cells is mediated by the mitochondrial
      pathway independent of death receptors.
AB  - BACKGROUND: Chronic infection with Helicobacter pylori is related to the
      pathogenesis of the noncardia carcinoma of the stomach. In this study we
      investigated the mechanisms of H. pylori-induced apoptosis in T lymphocytes,
      which could explain a mechanism of immune evasion facilitating chronic
      inflammation of the mucosa and gastric carcinogenesis. MATERIALS AND METHODS: The
      supernatant of H. pylori culture was used to study the mechanism of apoptosis
      induction in human leukaemia T cell lines Jurkat and CEM and in primary T cells.
      The cytotoxin associated gene A (CagA) and vacuolating cytotoxin A (Vac A)
      positive bacterial strain H. pylori 60190 (CagA(+), VacA(+)) and as a control the
      less toxic H. pylori strain Tx30a (CagA(-), VacA(-)) were used to produce the
      supernatant. Cell death was determined by DNA fragmentation and protein
      expression by Western blot. RESULTS: H. pylori 60190-induced apoptosis was
      neither blocked by inhibition of the death ligands TRAIL (TNF-related apoptosis
      inducing ligand), CD95L/FasL and TNF-alpha (tumour necrosis factor-a) in wild
      type Jurkat cells nor in FADD(def) (Fas-associated death domain protein) and
      caspase-8(def) subclones of the Jurkat cell line. Yet, the pancaspase inhibitor
      zVAD-fmk could inhibit up to 90% of H. pylori-induced apoptosis. Stable
      transfection of Jurkat wild type cells with Bcl-x(L and) Bcl-2 resulted in marked
      reduction of H. pylori-induced apoptosis, showing that the mitochondrial pathway
      is the key regulator. This is supported by the finding that surviving primary
      human lymphocytes upregulate Bcl-2 when exposed to H. pylori supernatant.
      CONCLUSIONS: H. pylori-induced apoptosis of T cells is mediated by the
      mitochondrial pathway and could create a local environment that facilitates life
      long infection by immune evasion.

PMID- 17217378
TI  - Expression profiling of PC-3 cell line variants and comparison of MIC-1
      transcript levels in benign and malignant prostate.
AB  - BACKGROUND: The mechanisms behind prostate cancer progression are largely
      unknown, but macrophage inhibitory cytokine 1 (MIC-1) has been suggested to be
      involved in tumour dissemination in vivo due to its reductive effect on cell
      adhesion. MATERIALS AND METHODS: We used two PC-3 prostate cancer epithelial cell
      line variants as tools to screen for gene expression differences during prostate
      cancer progression by cDNA microarray analysis. Selected genes were further
      analysed by Northern blot analysis using mRNA isolated from prostatic cell lines
      and tissues. MIC-1 expression was studied by in situ hybridization in archival
      patient specimens containing benign and malignant prostatic tissue. RESULTS: Gene
      expression of human collagen type VI, basement membrane heparan sulphate
      proteoglycan, integrin alpha 1, and fibronectin I were remarkably decreased in
      suspension-adapted PC-3 (saPC-3) cells, indicating a gene expression profile of
      reduced cell adhesion. Asparagine synthetase, serine protease 1, stanniocalcin
      homologue, NAD-dependent methylene tetrahydrate dehydrogenase cyclohydrolase
      (NMDMC), fortilin, and MIC-1 were overexpressed in saPC-3 cells. In prostate, the
      MIC-1 gene was mainly expressed in cancer tissue. However, MIC-1 transcripts were
      detected in benign tissue areas, especially in specimens containing prostate
      cancer with Gleason sum scores of 5-8. A significant inverse correlation
      (Spearman's rho correlation coefficient -0.928**) was observed between the ratio
      of cancerous to benign MIC-1 expression levels and Gleason scores. CONCLUSIONS:
      Differential expression of the MIC-1 gene occurs during prostate cancer
      progression. The transcript level of the MIC-1 gene in histologically benign
      tissue seems to approach that in paired cancer tissue concomitant with an
      increasing Gleason score.

PMID- 17217379
TI  - Lactate down-regulates cellular poly(ADP-ribose) formation in cultured human skin
      fibroblasts.
AB  - BACKGROUND: Polyadenosine diphosphate-ribose (poly(ADP-ribose)) is a nuclear
      polymer which is derived from nicotinamide adenine dinucleotide (NAD(+))
      catalysed by poly(ADP-ribose) polymerase 1 (PARP-1). Aside from the well known
      role of poly(ADP-ribosyl)ation (pADPR) in DNA repair, pADPR is also involved in
      other cellular processes such as apoptosis and gene expression. However, the
      factors that regulate the level of pADPR are not fully elucidated. In view of the
      fact that healing wounds contain high concentrations of lactate (10-15 mM) and
      exogenous lactate reduce the NAD(+) pool in cultured fibroblasts, we propose that
      high lactate lowers the level of nuclear pADPR. MATERIALS AND METHODS: Neonatal
      human dermal fibroblasts (NHDF) were plated to subconfluence and allowed to
      adhere. Cells were treated with 15 mM l-lactate and pADPR production was assessed
      by immunofluorescence analysis using 10H antibody. Difference in pADPR production
      was determined by calculation of positively stained cells compared to total cell
      numbers. Inhibition of PARP activity was tested by treatment with 100 microM 3
      aminobenzamide (3-AB). Specificity of the lactate effect on pADPR synthesis was
      verified by using the analogue d-lactate. The contents of nicotinamide adenine
      dinucleotide (NAD(+)) and its reduced form (NADH) in lactated and non-lactated
      cell cultures were quantified by the enzymatic cyclic assay. RESULTS: We found
      that exogenous l-lactate (15 mM) can significantly depress pADPR content in
      cultured fibroblasts. PARP-1 activity was inhibited by 3-AB and analogue d
      lactate showed no effect on pADPR synthesis. NAD(+)/NADH ratio was significantly
      lowered in lactated compared to non-lactated cell culture. CONCLUSIONS: Exogenous
      l-lactate (15 mM) can depress pADPR content in cultured fibroblasts. In view of
      the fact that healing wounds contain such high concentrations of lactate, we
      propose that down regulation of pADPR is associated with elevated tissue repair
      via pADPR dependent gene expression. This observation is important in
      understanding the stimulation of lactate-mediated protein expression during wound
      healing.

PMID- 17217380
TI  - Nasal nitric oxide in cystic fibrosis with and without humming.
AB  - BACKGROUND: Nasal nitric oxide (nNO) values are reduced in patients with cystic
      fibrosis (CF). Humming during nNO measurement increases nNO values in healthy
      subjects. Nasal NO is reduced in patients with CF, sinus disease or nasal polyps.
      Humming nNO values have not been reported in CF patients yet. Our aim was to
      explore humming nNO values in CF patients and assess whether nNO during humming
      is a better discriminator than silent nNO measurements in this patient group.
      MATERIALS AND METHODS: In a cross sectional study we measured nNO concentrations
      in healthy controls (HC) and in CF patients (n = 23 and 31, respectively). The
      participants held their breath for 10 s while air was passively extracted from
      one nostril with 700 mL min(-1) for direct NO measurements (NIOX
      chemiluminescence analyser). Subsequently nNO was measured during humming with
      the mouth closed for 10 s. RESULTS: Mean nNO in parts per billion (p.p.b.) (SD)
      during breath hold was 499 (164) and 240 (139), respectively. The median nNO peak
      (p.p.b., minimum-maximum) during humming was 1500 (425-4100) for HC and 120 (23
      500) for CF. There was a highly significant difference between nNO both with and
      without humming between CF and HC (P < 0.01). The sensitivity and specificity of
      nNO for detecting CF were better with humming. CONCLUSION: Nasal NO
      concentrations with and without humming are significantly decreased in CF.
      Humming nNO is an excellent discriminator between HC and CF and performs better
      than silent nNO.

PMID- 17217381
TI  - Circulating levels of copeptin, a novel biomarker, in lower respiratory tract
      infections.
AB  - BACKGROUND: Vasopressin has haemodynamic as well as osmoregulatory effects, and
      reflects the individual stress response. Copeptin is co-synthesized with
      vasopressin, directly mirroring vasopressin levels, but is more stable in plasma
      and serum. Both levels are increased in patients with septic shock. Lower
      respiratory tract infections (LRTI) are a precursor of sepsis. Thus, we
      investigated circulating levels and the prognostic use of copeptin for the
      severity and outcome in patients with LRTI. MATERIALS AND METHODS: Five hundred
      and forty-five consecutive patients with LRTI and 50 healthy controls were
      evaluated. Serum copeptin levels were measured with a new chemiluminescent
      sandwich immunoassay. RESULTS: Of the 545 patients, 373 had community-acquired
      pneumonia (CAP), 60 acute exacerbations of chronic obstructive pulmonary disease
      (COPD), 59 acute bronchitis, 13 exacerbations of asthma and 40 other final
      diagnoses. Copeptin levels were significantly higher in patients with LRTI as
      compared to controls (P < 0.001) with highest levels in patients with CAP.
      Copeptin levels increased with increasing severity of CAP, as classified by the
      pneumonia severity index (PSI) (P < 0.001). In patients who died, copeptin levels
      on admission were significantly higher as compared to levels in survivors [70.0
      (28.8-149.0) vs. 24.3 (10.8-43.8) pmol L(-1), P < 0.001]. The area under the
      receiver operating curve (AUC) for survival was 0.75 for copeptin, which was
      significantly higher as compared to C-reactive protein (AUC 0.61, P = 0.01),
      leukocyte count (AUC 0.59, P = 0.01) and similar to procalcitonin (AUC 0.68, P =
      0.21). CONCLUSIONS: Copeptin levels are increased with increasing severity of
      LRTI namely in patients with CAP and unfavourable outcome. Copeptin levels, as a
      novel biomarker, might be a useful tool in the risk stratification of patients
      with LRTI.

PMID- 17217382
TI  - FIP1L1/PDGFRA is a molecular marker of chronic eosinophilic leukaemia but not for
      systemic mastocytosis.

PMID- 17217383
TI  - Atypical APL including multiple translocations and abnormal response to
      micronuclei induction test.

PMID- 17217384
TI  - Effects of dietary energy intake and cold exposure on kinetics of plasma glucose
      metabolism in sheep.
AB  - An isotope dilution method using [U-(13)C]glucose injection was applied to
      determine the effects of dietary energy intake and cold exposure on plasma
      glucose metabolism in sheep. The sheep were assigned to two dietary treatments
      and were fed on diets containing either 100% or 160% of ME and both containing
      150% of dietary crude protein intake for maintenance. The sheep were exposed from
      a thermoneutral environment (23 degrees C) to a cold environment (2-4 degrees C)
      for 5 days. The isotope dilution method was performed on the 18th day in the
      thermoneutral environment and on the fifth day of cold exposure. Plasma
      concentrations of glucose and NEFA increased (p < 0.05) during cold exposure for
      both diets. Plasma glucose pool size remained unchanged (p = 0.67), but plasma
      glucose turnover rate tended to increase (p = 0.07) with increased energy intake.
      Both pool size and turnover rate of plasma glucose increased (p = 0.01 and p =
      0.0001, respectively) during cold exposure. No significant diet x environment
      interaction was detected. It is concluded that plasma glucose metabolism was
      influenced by both dietary energy intake and cold exposure, and plasma glucose
      metabolism in response to cold exposure was not modified by energy intake in
      sheep under the conditions (2-4 degrees C on the fifth day) of the present
      experiment.

PMID- 17217385
TI  - Effects of high-level dietary B-vitamins on performance, body composition and
      tissue vitamin contents of growing/finishing pigs.
AB  - Forty-eight growing pigs were randomly assigned to five dietary groups and penned
      individually. They received a diet based on barley, wheat, corn and soya bean
      meal according to requirement. The experimental groups were supplemented with
      400% or 800% of vitamins B(2), B(6) and pantothenic acid, or 400% or 800% of
      biotin, while all other vitamins were administered according to requirement.
      Growth performance, carcass characteristics, aspartate aminotransferase (AST),
      and content of vitamins in blood, liver and muscles were recorded. Growth
      performance showed no influence of supplementation, while backfat thickness in
      the group with 800% B(2)/B(6)/pantothenic acid was significantly higher. Content
      of B(2) in blood, liver and muscle was similar in all groups. Content of B(6) in
      blood and liver showed significant differences according to supplementation. The
      content of vitamin B(6) in muscle in the experimental groups was significantly
      higher than that in the control group. The content of pantothenic acid in blood
      and muscle in the experimental groups was significantly higher, while in liver
      all groups were significantly influenced by the supplementation level. Biotin
      content in liver showed no influence, but the content in plasma was significantly
      higher in the experimental groups and the content in muscle was significantly
      higher according to supplementation. The activity of AST showed no significant
      influence of the dietary vitamin level, but it was obviously decreased in the
      groups supplemented with biotin. The findings indicate that the dietary
      supplementation of vitamin B(2), B(6), pantothenic acid and biotin could not
      improve performance, but the contents in blood, liver and muscle.

PMID- 17217386
TI  - The influence of dietary linoleic and alpha-linolenic acid on body composition
      and the activities of key enzymes of hepatic lipogenesis and fatty acid oxidation
      in mice.
AB  - We have recently suggested that feeding the C18 polyunsaturated fatty acid, alpha
      linolenic acid (ALA), instead of linoleic acid (LA) reduced body fat in mice.
      However, the difference in body fat did not reach statistical significance, which
      prompted us to carry out this study using more animals and diets with higher
      contents of ALA and LA so that the contrast would be greater. The diets contained
      either 12% (w/w) LA and 3% ALA or 12% ALA and 4% LA. A low-fat diet was used as
      control. The diets were fed for 35 days. The proportion of body fat was not
      influenced by the type of dietary fatty acid. Plasma total cholesterol and
      phospholipids were significantly lower in ALA-fed mice than in mice fed LA.
      Activities of enzymes in the fatty acid oxidation pathway were significantly
      raised by these two diets when compared with the control diet. alpha-Linolenic
      acid vs. LA did not affect fatty acid oxidation enzymes. In mice fed the diet
      with LA activities of enzymes of de novo fatty acid synthesis were significantly
      decreased when compared with mice fed the control diet. alpha-Linolenic acid vs.
      LA feeding did not influence lipogenic enzymes. It is concluded that feeding mice
      for 35 days with diets either rich in LA or ALA did not significantly influence
      body composition.

PMID- 17217387
TI  - Assessment of zinc and copper status in weaned piglets in relation to dietary
      zinc and copper supply.
AB  - The aim of the study was to determine the effect of weaning and the effect of
      increasing dietary zinc concentrations on the zinc and copper status of weaned
      piglets (study 1) and to study the effect of high concentrations of dietary zinc
      and/or copper on zinc and copper status of weaned piglets (study 2). Study 1
      included 54 piglets (six litters of nine piglets). One piglet from every litter
      was killed 1 day before weaning. The remaining 48 piglets were allocated at
      weaning (28 days) to four dietary zinc treatments (100, 250, 1000 or 2500 ppm)
      and subsequently killed 1-2, 5-6 or 14-15 days after weaning. Study 2 included 48
      piglets (six litters of eight piglets) allocated to four dietary treatments,
      consisting of low or high dietary zinc (100 or 2500 ppm) in combination with low
      or high dietary copper (20 or 175 ppm). All piglets in study 2 were killed 5-7
      days after weaning. In both studies, the trace mineral status was assessed by
      zinc and copper concentrations and alkaline phosphatase (AP) activity in plasma
      and mucosal tissue. In study 2, lymphocyte metallothionein (MT) mRNA and
      intestinal mucosa MT mRNA concentrations were included as zinc status markers.
      The results showed that the zinc status, measured as zinc in plasma and mucosa,
      was not affected by weaning of the piglets. Plasma copper concentrations
      decreased during the first 2 weeks after weaning. High dietary copper
      concentrations did not affect the concentration of copper in plasma, but
      increased the concentration of copper in mucosa and the concentration of zinc in
      plasma. The dietary zinc treatments increased the zinc concentration in plasma as
      well as the zinc and MT mRNA concentration in mucosa. Lymphocyte MT mRNA
      concentrations did not reflect the differences in dietary zinc supplementation.

PMID- 17217388
TI  - Regional differences in the effects of various doses of cerulein upon the small
      intestinal migrating motor complex in fasted and non-fasted sheep.
AB  - There are no precise data concerning the effect of cerulein on the small
      intestinal migrating motor complex (MMC) in sheep. Thus, the effort was directed
      towards the elucidation of the role of cerulein, a cholecystokinin (CCK)
      amphibian analogue, in the regulation of MMC cycle in conscious fasted and non
      fasted sheep in various regions of the small intestine. In six sheep, equipped
      with bipolar electrodes in the entire small intestine and with one duodenal
      strain gauge force transducer in four of these animals, the continuous
      myoelectric and motor activity recordings were performed. During control period,
      two normal consecutive MMC cycles were recorded in fasted and non-fasted animals
      and then cerulein was slowly injected at the dose 1 (during 30 s), 10 (during 30
      s or 60 s) or 100 ng/kg (during 30 s, 60 s or 120 s) or infused at the dose 0.5
      or 1.5 ng/kg/min during 60 min. After cerulein administration at least two
      consecutive MMC cycles were also recorded. It was found that cerulein in moderate
      and higher doses injected in both fasted and non-fasted animals, especially
      during phase 2a or 2b MMC, inhibited phase 3 in the duodenum in at least one
      third of the experiments and significantly increased the MMC cycle duration. The
      application of 100 ng/kg of cerulein during 120 s in the course of phase 2b MMC
      prolonged cycle duration from 70 +/- 21 to 113 +/- 19 min (p < 0.05) or from 51
      +/- 18 to 113 +/- 19 min (p < 0.01) in fasted and non-fasted sheep respectively.
      The first phase 3 MMC arriving after cerulein administration at the highest dose
      was usually abnormal in approximately 60% of the experiments. The second phase 3
      observed following the hormone injection was abnormal much less frequently and to
      the lesser extent. Furthermore, both cerulein doses significantly shortened the
      duration of phase 3 MMC either in fasted (from approximately 5.5-6.5 cpm to 4-5
      cpm) or in non-fasted sheep (from approximately 4.5-5.5 to 3-4.5 cpm). The
      effects of cerulein exhibited the dose-response character. They were more
      pronounced when cerulein was injected during phase 2b or 2a MMC when compared
      with phase 1 MMC. The effects of cerulein on the ileal MMC were less evident,
      although the inhibition of the ileal phase 3 in response to both higher injected
      doses was observed occasionally. Infusions of cerulein in non-fasted sheep
      exerted similar effects as cerulein injections. It was stated that cerulein
      exerts marked regulatory effect upon the small-intestinal MMC in sheep. Although
      it remains uncertain whether the efficient doses of cerulein used in the present
      study correspond to physiological or pharmacological doses of CCK it seems likely
      that most of these doses were physiological. Thus, it is concluded that cerulein
      participates in the control of MMC cycles in the digestive and interdigestive
      states in sheep. It is possible that CCK is a physiological regulator of the
      ovine small-intestinal MMC.

PMID- 17217389
TI  - Blood vitamin concentrations in privately owned dogs fed non-standardized
      commercial diets and after intake of diets with specified vitamin concentrations.
AB  - The objective was to investigate in a survey study the blood vitamin
      concentrations in healthy dogs fed non-specified commercial complete diets and in
      an intervention study to determine the effects of defined dietary vitamin intakes
      on blood vitamin levels and hair and skin condition. Sixty-four privately owned
      dogs, aged from 1 to 8 years, without history of skin or coat problems were
      included. All animals were fed commercial complete diets with uncertain vitamin
      concentrations before enrolment. The animals were assigned, according to weight
      and gender, to four groups with graded vitamin intakes. The blood vitamin levels
      and skin and coat quality of the dogs were investigated at days 0 and day 122.
      Coat and hair condition was not influenced by the experimental diets. The retinol
      concentrations were reduced at the end of the experiment compared with the
      baseline levels, retinyl esters were not influenced. 25-Hydroxycholecalciferol
      decreased in all groups, alpha-tocopherol was constant or tended to decrease.
      Ascorbic acid, thiamine pyrophosphate and riboflavin concentrations were not
      affected by treatment, flavin adenine dinucleotide and pyridoxal-5'-phosphate
      were partially reduced on day 122. Cobalamin, pantothenate and biotin
      concentrations increased with higher dietary intakes, folate levels in tendency.
      In conclusion, this study gives a survey of blood vitamin concentrations in
      healthy dogs and provides a data base for the evaluation of the vitamin status in
      health and disease.

PMID- 17217390
TI  - Molecular characterisation of the gut microflora of healthy and inflammatory
      bowel disease cats using fluorescence in situ hybridisation with special
      reference to Desulfovibrio spp.
AB  - Inflammatory bowel disease (IBD) is a common cause of chronic large bowel
      diarrhoea in cats. Although the aetiology of IBD is unknown, an immune-mediated
      response to a luminal antigen is thought to be involved. As knowledge concerning
      the colonic microflora of cats is limited and requires further investigation, the
      purpose of this study was to determine the presence of specific bacterial groups
      in normal and IBD cats, and the potential role they play in the health of the
      host. Total bacterial populations, Bacteroides spp., Bifidobacterium spp.,
      Clostridium histolyticum subgp., Lactobacillus-Enterococcus subgp. and
      Desulfovibrio spp. were enumerated in 34 healthy cats and 11 IBD cats using
      fluorescence in situ hybridisation. The study is one of the first to show the
      presence of Desulfovibrio in cats. Total bacteria, Bifidobacterium spp. and
      Bacteroides spp. counts were all significantly higher in healthy cats when
      compared with IBD cats, whereas Desulfovibrio spp. (producers of toxic sulphides)
      numbers were found to be significantly higher in colitic cats. The information
      obtained from this study suggests that modulation of bacterial flora by
      increasing bifidobacteria and decreasing Desulfovibrio spp. may be beneficial to
      cats with IBD. Dietary intervention may be an important aspect of their
      treatment.

PMID- 17217391
TI  - Effect of energy restriction and re-alimentation in Belgian Blue double-muscled
      beef cows on digestibility and metabolites.
AB  - Four groups of five non-lactating and non-pregnant Belgian Blue double-muscled
      (BBDM) cows were used to investigate the effect of energy level (E) on digestion,
      and blood and urine metabolites. The energy levels of the groups, applied indoors
      during a 140-day restriction period, were 100%, 90%, 80% or 70% of their energy
      requirements (E100, E90, E80, E70) respectively. Afterwards, animals grazed on
      the same swards for 203 days (re-alimentation period). Balance trials were
      conducted at the end of the restriction period (BT1) and at the end of the re
      alimentation period (BT2). Blood was sampled at the end of these trials. Diets
      consisted of maize silage and straw (80/20 on a dry matter basis) and a mineral
      vitamin premix, fed at the appropriate E during BT1, or maize silage and a
      mineral-vitamin premix, fed at 125% of the maintenance requirements, during BT2.
      Significant increases of the digestibility coefficients were found during BT1
      when E decreased, resulting in a better net energy capture of 7% for E70 compared
      with E100 (p < 0.05). Slightly, but non-significantly higher digestibility
      coefficients were observed for decreasing E during BT2. Plasma concentrations of
      glucose and creatinine did not differ between treatments during BT1, while
      differences were found for triacylglycerols and alpha-amino nitrogen. A tendency
      for a linear increase was observed for non-esterified fatty acids with decreasing
      E. Differences in blood metabolite concentrations disappeared in BT2. Urinary
      creatinine excretion was not affected by E, while body nitrogen loss increased
      linearly with energy restriction in BT1. No differences were found during BT2,
      suggesting that non-lactating and non-pregnant BBDM cows are able to adapt to a
      cyclic change of body weight and body reserves. These data show that restricted
      cows mobilized body fat as well as body protein. It is concluded that the
      qualitative aspects of metabolism during energy restriction are comparable in
      double-muscled cows with those in non-double-muscled animals, although the
      magnitude of the effects may be different.

PMID- 17217392
TI  - Effects of dexamethasone on mRNA abundance of nuclear receptors and hepatic
      nuclear receptor target genes in neonatal calves.
AB  - Hepatic nuclear receptors (NR), particularly constitutive androstane receptor
      (CAR) and pregnane X receptor (PXR), are involved in the coordinated
      transcriptional control of genes that encode proteins involved in the metabolism
      and detoxification of xeno- and endobiotics. A broad spectrum of metabolic
      processes are mediated by NR acting in concert with ligands such as
      glucocorticoids. This study examined the role of dexamethasone on hepatic mRNA
      expression of CAR, PXR and several NR target genes. Twenty-eight male calves were
      allotted to one of four treatment groups in a 2 x 2 arrangement of treatments:
      feed source (colostrum or milk-based formula) and glucocorticoid administration
      (twice daily intramuscular dexamethasone). Liver biopsies were obtained at 5 days
      of age. Real-time reverse transcription polymerase chain reaction was used to
      quantify mRNA abundances. No effects of feed source on mRNA abundances were
      observed. For the NR examined, mRNA abundance of both CAR and PXR in
      dexamethasone-treated calves was lower (p < 0.05) by 39% and 40%, respectively,
      than in control calves. Abundance of NR target genes exhibited a mixed response.
      SULT1A1 mRNA abundance was 39% higher (p < 0.05) in dexamethasone-treated calves
      compared with control calves. mRNA abundance of CYP2C8 tended also to be higher
      (+44%; p = 0.053) after dexamethasone treatment. No significant treatment effects
      (p > 0.10) were observed for mRNA abundances of CYP3A4, CYP2E1, SULT2A1, UGT1A1
      or cytochrome P450 reductase (CPR). In conclusion, an enhanced glucocorticoid
      status, induced by pharmacological amounts of dexamethasone, had differential and
      in part unexpected effects on NR and NR target systems in 5-day-old calves. Part
      of the unexpected responses may be due the immaturity of NR and NR receptor
      target systems.

PMID- 17217393
TI  - Plasma growth hormone concentrations in female mithun (Bos frontalis) of
      different ages: relations with age and body weight.
AB  - The role of growth hormone (GH) in postnatal somatic growth is well established.
      Its basal level and relation to growth performance in different age group mithun
      (Bos frontalis), a semiwild ruminant has not been characterized until now. To
      estimate the normal blood GH level and also to assess the influence of age and
      body weight (BW) on blood GH level in captive mithuns, a total of 65 female
      mithuns was divided into six age groups (group I, 0-6 months; group II, >6-12
      months; group III, >1-2 years; group IV, >2-2.5 years; group V, >2.5-3.0 years
      and group VI, >3.0 years). Blood samples collected weekly for six consecutive
      weeks were assayed for GH. GH was also estimated in the samples collected from
      six growing mithuns at -60, -45, -30, -15, -10, -5 and 0 min prior to GH
      releasing hormone (GHRH) administration for calculation of basal GH level and at
      5, 10, 15, 30 min and thereafter at 15-min interval up to 8 h post-GHRH to assess
      blood GH response following GHRH administration in growing mithuns. For
      calculation of basal plasma GH in adult mithuns, GH was measured in blood samples
      collected at 30-min interval for 24 h from four animals. BW of all animals was
      recorded on two consecutive days per week and average of weekly BW was considered
      for growth rate calculation. It was found that both mean GH and GH per 100 kg BW
      between the age groups differ (p < 0.01). With increasing age and BW, GH and GH
      per 100 kg BW both decreased (p < 0.01). The age group with higher plasma GH and
      GH per 100 kg BW showed higher growth rates (r = 0.83 and 0.97 respectively).
      Interestingly, mean plasma GH for six consecutive weeks in all the groups showed
      much greater GH concentration (group I, 86.6 +/- 9.7 ng/ml to group VI 33.2 +/- 5
      ng/ml) than reported in other species. Mean basal plasma GH calculated in growing
      and adult mithuns was 29.6 +/- 4.01 ng/ml and around 25 +/- 3.6 ng/ml
      respectively. The GH peak (444 +/- 21.3 ng/ml) was registered at 15 min post-GHRH
      administration in growing mithuns. In conclusion, age and BW influence plasma GH
      and GH per 100 kg BW but the latter is a better indicator of growth. The basal
      plasma GH and GH response to GHRH administration is six to eight and four to five
      times higher in mithun than in other species reported so far. An accurate
      assessment of the relationship between GH profiles and protein metabolism, proper
      receptor level study for GH action at the cellular level and the interaction of
      GH with other growth factors awaits better understanding of higher GH in this
      unique species.

PMID- 17217394
TI  - Nutrient digestibility of rabbit does in different stages of reproductive cycle
      under tropical conditions.
AB  - Effect of stages of reproductive cycle on body weight, feed intake and apparent
      nutrient digestibility of rabbits was investigated. Pregnant/lactating (PL) does
      increased their feed intake above pregnant lactating does. Dry matter (DM)
      digestibility was higher in pregnant does than in lactating, PL or open does.
      Digestibility of crude fibre, crude protein (CP) and nitrogen-free extractives
      (NFE) were significantly higher for open and pregnant does than lactating and PL
      does. Ether extract (EE) digestibility was similar for pregnant, lactating and PL
      does. Digestible CP requirement of does increased with physiological state from
      open to PL states. Open and pregnant does were meeting their protein requirement
      while lactating and PL does were not meeting their requirement. Feed intake was
      higher for first week pregnant, fourth week pregnant, first week lactating, first
      week pregnant/fourth week lactating and second week pregnant/fourth week
      lactating does than open does. DM digestibility was higher for first and fourth
      week pregnant does than the other physiological stages. EE digestibility was
      similar for all physiological stages. CP digestibility was higher in fourth week
      pregnant does than the other physiological stages. Fourth week pregnant does had
      higher NFE digestibility than first and fourth week lactating and the various
      stages of concurrent pregnant and lactating does. Open does, first and fourth
      week pregnant does were meeting their protein requirement while does in the first
      and fourth week of lactating and stages of concurrent PL were not meeting their
      requirement.

PMID- 17217395
TI  - Residues of veterinary drugs at injection sites.
AB  - Residues of veterinary drugs have potential implications for human food safety
      and international trade in animal-derived food commodities. A particular concern
      is the slow depletion of residues of some injectable formulations from the site
      of administration. Licensing authorities have adopted different approaches to the
      human food safety assessment of injection site residues. European agencies apply
      the maximum residue limit (MRL) for muscle to muscle at the injection site and
      specify a withdrawal period sufficient to ensure the ingestion of a 300 g portion
      of muscle, if comprised entirely of injection site tissue, does not exceed the
      acceptable daily intake. The agencies in Australia, Canada and the USA also
      exclude injection site residues from the MRL-setting process. These agencies
      evaluate the risk to consumers posed by potential acute manifestations resulting
      from the infrequent ingestion of injection site residues based on acute dietary
      exposure considerations. While all of these approaches protect the safety of
      consumers, the adoption of different approaches has potential implications for
      residue surveillance programs in the international trade in meat. In particular,
      when an exporting country establishes standards for residues at injection sites
      based on acute dietary exposure considerations and the importing country assesses
      these residues against the MRL for muscle, the unnecessary condemnation of meat
      and disruption to market access may result. The latter may represent a potential
      economical impost to the exporting country. An internationally harmonized
      approach to the risk analysis of residues of veterinary drugs at injection sites,
      which protects the safety of consumers and facilitates the international trade in
      meat, is needed.

PMID- 17217396
TI  - Pharmacokinetic-pharmacodynamic integration of danofloxacin after intravenous,
      intramuscular and subcutaneous administration to rabbits.
AB  - The pharmacokinetics of danofloxacin was studied following intravenous (i.v.),
      intramuscular (i.m.) and subcutaneous (s.c.) administration of 6 mg/kg to healthy
      rabbits. Danofloxacin concentration were determined by high-performance liquid
      chromatography assay with fluorescence detection. Minimal inhibitory
      concentrations (MICs) assay of danofloxacin against 30 strains of Staphylococcus
      aureus from several European countries was performed in order to compute
      pharmacodynamic surrogate markers. The danofloxacin plasma concentration versus
      time data after i.v. administration could best be described by a two-compartment
      open model. The disposition of i.m. and subcutaneously administered danofloxacin
      was best described by a one-compartment model. The terminal half-life for i.v.,
      i.m. and s.c. routes was 4.88, 6.70 and 8.20 h, respectively. Clearance value
      after i.v. dosing was 0.76 L/kg.h. After i.m. administration, the absolute
      bioavailability was mean (+/-SD) 102.34 +/- 5.17% and the Cmax was 1.87 mg/L.
      After s.c. administration, the absolute bioavailability was mean (+/-SD) 96.44 +/
      5.95% and the Cmax was 1.79 mg/L. Danofloxacin shows a favourable
      pharmacokinetics profile in rabbits reflected by parameters such as a long half
      life and a high bioavailability. However, in consideration of the low AUC/MIC
      indices obtained, its use by i.m. and s.c. route against the S. aureus strains
      assayed in this study cannot be recommended given the risk for selection of first
      mutant subpopulations.

PMID- 17217397
TI  - P-glycoprotein-mediated transport of oxytetracycline in the Caco-2 cell model.
AB  - ATP-dependent drug transporters such as P-glycoprotein (P-gp), multi-drug
      resistance associated protein (MRP2) and breast cancer resistant protein (BCRP)
      are expressed at the brush border membrane of enterocytes. These efflux
      transporters excrete their substrates, among other various classes of
      antibiotics, into the lumen thus reducing net absorption as indicated by a low
      bioavailability after oral administration. Oxytetracycline (OTC) has been used
      for decennia in veterinary medicine for its extensive spectrum of antimicrobial
      activity. A major limitation has been, and still remains, its low bioavailability
      following oral administration. The present study aimed to investigate to what
      extent this low bioavailability is attributable to the fact that OTC is a
      substrate for one or more efflux transporters. As an experimental model to study
      the transmembrane transport of OTC, differentiated Caco-2 cells grown as
      monolayers on permeable supports were used. With this model it was shown that the
      secretion of OTC is slightly higher than its absorption. PSC833, a potent
      inhibitor of P-gp, decreased the secretion of OTC without affecting its
      absorption, while the MRP-inhibitor MK571 did not exert any effect. These data
      indicate that OTC is a substrate for P-gp. The affinity of OTC to these
      transporters seems to be rather low, as suggested by the low efflux ratio of
      1:1.3. In competition experiments, OTC decreased the effluxes of other P-gp
      substrates such as Rhodamine123 and ivermectin. These findings are of clinical
      relevance, as they clearly indicate potential drug-drug interactions at the level
      of P-gp-mediated drug transport.

PMID- 17217398
TI  - Pharmacokinetics of florfenicol and its major metabolite, florfenicol amine, in
      rabbits.
AB  - The pharmacokinetics of florfenicol and its active metabolite florfenicol amine
      were investigated in rabbits after a single intravenous (i.v.) and oral (p.o.)
      administration of florfenicol at 20 mg/kg bodyweight. The plasma concentrations
      of florfenicol and florfenicol amine were determined simultaneously by an LC/MS
      method. After i.v. injection, the terminal half-life (t(1/2lambdaz)), steady
      state volume of distribution, total body clearance and mean residence time of
      florfenicol were 0.90 +/- 0.20 h, 0.94 +/- 0.19 L/kg, 0.63 +/- 0.06 L/h/kg and
      1.50 +/- 0.34 h respectively. The peak concentrations (C(max)) of florfenicol
      (7.96 +/- 2.75 microg/mL) after p.o. administration were observed at 0.90 +/-
      0.38 h. The t(1/2lambdaz) and p.o. bioavailability of florfenicol were 1.42 +/-
      0.56 h and 76.23 +/- 12.02% respectively. Florfenicol amine was detected in all
      rabbits after i.v. and p.o. administration. After i.v. and p.o. administration of
      florfenicol, the observed Cmax values of florfenicol amine (5.06 +/- 1.79 and
      3.38 +/- 0.97 microg/mL) were reached at 0.88 +/- 0.78 and 2.10 +/- 1.08 h
      respectively. Florfenicol amine was eliminated with an elimination half-life of
      1.84 +/- 0.17 and 2.35 +/- 0.94 h after i.v. and p.o. administration
      respectively.

PMID- 17217399
TI  - Lack of inhibitory effects of several fluoroquinolones on cytochrome P-450 3A
      activities at clinical dosage in dogs.
AB  - Inhibitory effects of several fluoroquinolones (FQs) on liver CYP3A activities
      were examined by in vitro and in vivo tests in dogs. Midazolam (MDZ)
      hydroxylation rate was used to determine the CYP3A activities in liver
      microsomes. Enrofloxacin (EFX), ofloxacin (OFX) orbifloxacin (OBFX) and
      ciprofloxacin (CFX) were tested. None of the FQs changed Vmax, Km or intrinsic
      clearance (Vmax/Km) of MDZ. For in vivo test, we examined the effects of oral
      administration of EFX and OFX on the pharmacokinetics of quinidine (QN), a CYP3A
      substrate. EFX or OFX (10 mg/kg) was administered once a day for 3 days. QN (2
      mg/kg) was intravenously injected at 2 h after the final dose of FQs
      administration. The same dose of QN was intravenously injected 3 weeks before the
      start of FQs administration for control. Neither EFX nor OFX changed the
      pharmacokinetic parameters of QN. These in vitro and in vivo consisted results
      suggest that these FQs lack the inhibitory effects on CYP3A activities in dogs.
      Hence, given these results, the risk of drug-drug interaction is unlikely to
      occur between FQs and CYP3A substrates in clinical situation in dogs.

PMID- 17217400
TI  - Pharmacokinetics of etodolac in the horse following oral and intravenous
      administration.
AB  - The purpose of this study was to determine the pharmacokinetics of etodolac
      following oral and intravenous administration to six horses. Additionally, in
      vitro cyclooxygenase (COX) selectivity assays were performed using equine whole
      blood. Using a randomized two-way crossover design, horses were administered
      etodolac (20 mg/kg) orally or intravenously, with a minimum 3-week washout
      period. Plasma samples were collected after administration for analysis using
      high pressure liquid chromatography with ultraviolet detection. Following
      intravenous administration, etodolac had a mean plasma half-life (t(1/2)) of 2.67
      h, volume of distribution (Vd) of 0.29 L/kg and clearance (Cl) of 234.87 mL/h kg.
      Following oral administration, the average maximum plasma concentration (Cmax))
      was 32.57 mug/mL with a t(1/2) of 3.02 h. Bioavailability was approximately
      77.02%. Results of in vitro COX selectivity assays showed that etodolac was only
      slightly selective for COX-2 with a COX-1/COX-2 selectivity ratio effective
      concentration (EC)50 of 4.32 and for EC80 of 4.77. This study showed that
      etodolac is well absorbed in the horse after oral administration, and may offer a
      useful alternative for anti-inflammatory treatment of various conditions in the
      horse.

PMID- 17217401
TI  - Intravenous and intramuscular pharmacokinetics of a single-daily dose of disodium
      fosfomycin in cattle, administered for 3 days.
AB  - Pharmacokinetic parameters of fosfomycin in cattle were determined after
      administration of buffered disodium fosfomycin either intravenously (i.v.) or
      intramuscularly (i.m.) at a dose of 20 mg/kg/day for 3 days. Calculated
      concentrations at time zero and maximum serum concentrations were 34.42 and 10.18
      mug/mL, respectively. The variables determined, the elimination half-life of the
      drug remained unchanged during the 3 days ( = 1.33 +/- 0.3 h for the i.v. route
      and = 2.17 +/- 0.4 h for the i.m. route). Apparent volumes of distribution
      suggest moderated distribution out of the central compartment (V(darea) = 673 mL
      +/- 27 mL/kg and V(dss) = 483 +/- 11 mL/kg). Bioavailability after i.m.
      administration was 74.52%. Considering fosfomycin as a time-dependent
      antibacterial drug, plasma concentration vs. time profiles obtained in this
      study, suggest that clinically effective plasma concentrations of fosfomycin
      could be obtained for up to 8 h following i.v. administration and approximately
      10 h after i.m. injection of 20 mg/kg, for susceptible bacteria. In addition to
      residue studies in milk and edible tissues, a series of clinical assessments,
      using fosfomycin at 20 mg/kg b.i.d. or t.i.d. are warranted before this
      antibacterial drug should be considered for use in cattle.

PMID- 17217402
TI  - Oral pharmacokinetic and pharmacodynamic effects of FTY720 in cats.
AB  - The aim of the study was to determine pharmacokinetic and pharmacodynamic
      profiles of FTY720 in cats and identify any toxic side effects. Six adult cats
      were used for the experimental study. Single oral dosages were tested at 0.05,
      0.3 and 1.0 mg/kg. Whole blood drug concentration, total white blood cell and
      differential counts were monitored. Flow cytometry evaluated the effects on
      lymphocyte subsets. A toxicity study consisted of cats receiving a dose of 0.15
      mg/kg daily for 30 days. Daily observation, physical examination and bloodwork
      were evaluated to assess for toxicity. All single doses resulted in > or =80%
      reduction in circulating lymphocytes within 12 h after administration, with the
      duration of lymphopenia being dose dependent. CD4+ and CD5+ T cells were
      specifically depleted. Peripheral neutrophils declined by approximately 70% at
      all dosages tested. No other toxic side effects were observed. Results of this
      study suggest that FTY720 is effective at inducing a peripheral lymphopenia in
      cats without any toxic side effects. Currently, cats appear to be the only
      species in which FTY720 induces a neutropenia. This study provides the foundation
      for future clinical transplantation trials using FTY720 in cats. By using
      combination therapy of FTY720 and low dose cyclosporine, the incidence of serious
      side effects may be reduced while still preventing allograft rejection.

PMID- 17217403
TI  - Pharmacokinetics of a new long acting endectocide formulation containing 2.25%
      ivermectin and 1.25% abamectin in cattle.
AB  - The objective of this study was to determine the kinetic parameters of a new
      formulation that contained 2.25% ivermectin combined with 1.25% abamectin in
      bovine plasma. The results for 2.25% ivermectin: Cmax (37.11 ng/mL +/- 7.42),
      Tmax (16 days +/- 5.29), T(1/2) (44.62 days +/- 53.89), AUC (928.2 ng x day/mL +/
      153.83) and MRT (36.73 days +/- 33.64), and for 1.25% abamectin: Cmax (28.70
      ng/mL +/- 9.54), Tmax (14 days +/- 4.04), T(1/2) (15.40 days +/- 11.43), AUC
      (618.05 ng x day/mL +/- 80.27) and MRT (20.79 days +/- 8.43) suggest that this
      combination of 2.25% ivermectin + 1.25% abamectin possesses properties that give
      this pharmaceutical formula a longer activity time than two of the commercial
      products tested (1% ivermectin and 1% abamectin), and showed similarity to 3.15%
      ivermectin.

PMID- 17217404
TI  - A competitive enzyme-linked immunosorbent assay for determination of
      chloramphenicol.
AB  - Chloramphenicol is a broad-spectrum antibiotic shown to have specific activity
      against a wide variety of organisms that are causative agents of several disease
      conditions in domestic animals. Chloramphenicol has been banned for use in food
      producing animals for its serious adverse toxic effects in humans. Due to the
      harmful effects of chloramphenicol residues livestock products should be free of
      any traces of these residues. Several analytical methods are available for
      chloramphenicol analysis but sensitive methods are required in order to ensure
      that no traces of chloramphenicol residues are present in edible animal products.
      In order to prevent the illegal use of chloramphenicol, regulatory control of its
      residues in food of animal origin is essential. A competitive enzyme-linked
      immunosorbent assay for chloramphenicol has been locally developed and optimized
      for the detection of chloramphenicol in sheep serum. In the assay,
      chloramphenicol in the test samples and that in chloramphenicol-horseradish
      peroxidase conjugate compete for antibodies raised against the drug in camels and
      immobilized on a microtitre plate. Tetramethylbenzidine-hydrogen peroxide
      (TMB/H2O2) is used as chromogen-substrate system. The assay has a detection limit
      of 0.1 ng/mL of serum with a high specificity for chloramphenicol. Cross
      reactivity with florfenicol, thiamphenicol, penicillin, tetracyclines and
      sulfamethazine was not observed. The assay was able to detect chloramphenicol
      concentrations in normal sheep serum for at least 1 week after intramuscular
      injection with the drug at a dose of 25 mg/kg body weight (b.w.). The assay can
      be used as a screening tool for chloramphenicol use in animals.

PMID- 17217405
TI  - Pharmacokinetics and milk penetration of difloxacin after intravenous,
      subcutaneous and intramuscular administration to lactating goats.
AB  - The single-dose disposition kinetics of difloxacin were determined in clinically
      normal lactating goats (n = 6) after intravenous (i.v.), subcutaneous (s.c.) and
      intramuscular (i.m.) administration of 5 mg/kg. Difloxacin concentrations were
      determined by high performance liquid chromatography with fluorescence detection.
      The concentration-time data were analysed by compartmental and noncompartmental
      kinetic methods. Steady-state volume of distribution (V(ss)) and total body
      clearance (Cl) of difloxacin after i.v. administration were estimated to be 1.16
      +/- 0.26 L/kg and 0.32 +/- 0.05 L/h x kg respectively. Following s.c. and i.m.
      administration difloxacin achieved maximum plasma concentrations of 1.33 +/- 0.25
      and 1.97 +/- 0.40 mg/L at 3.37 +/- 0.36 and 1.79 +/- 1.14 h respectively. The
      absolute bioavailabilities after s.c. and i.m. routes were 90.16 +/- 11.99% and
      106.79 +/- 13.95% respectively. Difloxacin penetration from the blood into the
      milk was extensive and rapid, and the drug was detected for 36 h after i.v. and
      s.c. dosing, and for 72 h after i.m. administration.

PMID- 17217406
TI  - Pharmacokinetics of erythromycin in nonlactating and lactating goats after
      intravenous and intramuscular administration.
AB  - The objectives of this work were to compare the pharmacokinetics of erythromycin
      administered by the intramuscular (i.m.) and intravenous (i.v.) routes between
      nonlactating and lactating goats and to determine the passage of the drug from
      blood into milk. Six nonpregnant, nonlactating and six lactating goats received
      erythromycin by the i.m. (15 mg/kg) and the i.v. (10 mg/kg) routes of
      administration. Milk and blood samples were collected at predetermined times.
      Erythromycin concentrations were determined by microbiological assay. Results are
      reported as mean +/- SD. Comparison of the pharmacokinetic profiles between
      nonlactating and lactating animals after i.v. administration indicated that
      significant differences were found in the mean body clearance (8.38 +/- 1.45 vs.
      3.77 +/- 0.83 mL/kg x h respectively), mean residence time (0.96 +/- 0.20 vs.
      3.18 +/- 1.32 h respectively), area under curve from 0 to 12 h (AUC(0-12)) (1.22
      +/- 0.22 vs. 2.76 +/- 0.58 microg x h/mL respectively) and elimination half-life
      (1.41 +/- 1.20 vs. 3.32 +/- 1.34 h); however, only AUC(0-12) showed significant
      differences after the i.m. administration. Passage of erythromycin in milk was
      high (peak milk concentration/peak serum concentration, 2.06 +/- 0.36 and AUC(0
      12milk)/AUC(0-12serum),6.9 +/- 1.05 and 2.37 +/- 0.61 after i.v. and i.m.
      administrations respectively). We, therefore, conclude that lactation affects
      erythromycin pharmacokinetics in goats.

PMID- 17217407
TI  - Pharmacokinetics of altrenogest in horses.
AB  - The Federation Equestre Internationale has permitted the use of altrenogest in
      mares for the control of oestrus. However, altrenogest is also suspicious to
      misuse in competition horses for its potential anabolic effects and suppression
      of typical male behaviour, and thus is a controlled drug. To investigate the
      pharmacokinetics of altrenogest in horses we conducted an elimination study. Five
      oral doses of 44 mug/kg altrenogest were administered to 10 horses at a dose
      interval of 24 h. Following administration blood and urine samples were collected
      at appropriate intervals. Altrenogest concentrations were measured by liquid
      chromatography-tandem mass spectrometry. The plasma levels of altrenogest reached
      maximal concentrations of 23-75 ng/mL. Baseline values were achieved within 3
      days after the final administration. Urine peak concentrations of total
      altrenogest ranged from 823 to 3895 ng/mL. Twelve days after the final
      administration concentrations were below the limit of detection (ca 2 ng/mL).

PMID- 17217408
TI  - Comment on Guenette, S.A., Beaudry, F., Marier, J.F., and Vachon, P. (2006).
      Pharmacokinetics and anesthetic activity of eugenol in male Sprague-Dawley rats.
      J. Vet. Pharmacol. Ther. 29, 265-270.

PMID- 17217410
TI  - A role of local signalling in the establishment and maintenance of the
      asymmetrical architecture of a neuron.
AB  - Significant progress has been made in the identification of intrinsic and
      extrinsic factors involved in the development of nervous system. It is remarkable
      that the establishment and maintenance of the asymmetrical architecture of a
      neuron is coordinated by a limited repertoire of signalling machineries. However,
      the details of signalling mechanisms responsible for creating specificity and
      diversity required for proper development of the nervous system remain largely to
      be investigated. An emerging body of evidence suggests that specificity and
      diversity can be achieved by differential regulation of signalling components at
      distinct subcellular localizations. Many aspects of neuronal polarization and
      morphogenesis are attributed to localized signalling. Further diversity and
      specificity of receptor signalling can be achieved by the regulation of molecules
      outside the cell. Recent evidence suggests that extracellular matrix molecules
      are essential extrinsic cues that function to foster the growth of neurons.
      Therefore, it is important to understand where the signalling machineries are
      activated and how they are combined with other factors in order to understand the
      molecular mechanism underlying neuronal development.

PMID- 17217411
TI  - Transcription of rat TRPV1 utilizes a dual promoter system that is positively
      regulated by nerve growth factor.
AB  - The capsaicin receptor, also known as 'transient receptor potential vanilloid
      receptor subtype 1' (TRPV1, VR1), is an ion channel subunit expressed in primary
      afferent nociceptors, which plays a critical role in pain transduction and
      thermal hyperalgesia. Increases in nociceptor TRPV1 mRNA and protein are
      associated with tissue injury-inflammation. As little is understood about what
      controls TRPV1 RNA transcription in nociceptors, we functionally characterized
      the upstream portion of the rat TRPV1 gene. Two functional rTRPV1 promoter
      regions and their transcription initiation sites were identified. Although both
      promoter regions directed transcriptional activity in nerve growth factor (NGF)
      treated rat sensory neurons, the upstream Core promoter was the most active in
      cultures enriched in sensory neurons. Because NGF is a key modulator of
      inflammatory pain, we examined the effect of NGF on rTRPV1 transcription in PC12
      cells. NGF positively regulated transcriptional activity of both rTRPV1 promoter
      regions in PC12 cells. We propose that the upstream regulatory region of the
      rTRPV1 gene is composed of a dual promoter system that is regulated by NGF. These
      findings support the hypothesis that NGF produced under conditions of tissue
      injury and/or inflammation directs an increase of TRPV1 expression in nociceptors
      in part through a transcription-dependent mechanism.

PMID- 17217412
TI  - Copper ions disrupt dopamine metabolism via inhibition of V-H+-ATPase: a possible
      contributing factor to neurotoxicity.
AB  - The involvement of copper in the pathophysiology of neurodegeneration has been
      well documented but is not fully understood. Commonly, the effects are attributed
      to increased reactive oxygen species (ROS) production due to inherent redox
      properties of copper ions. Here we show copper can have physiological effects
      distinct from direct ROS production. First, we show that extragranular free
      copper inhibits the vesicular H(+)-ATPase of resealed chromaffin granule ghosts.
      Extragranular ascorbate potentiates this inhibition. The inhibition is mixed type
      with K(is) = 6.8 +/- 2.8 micromol/L and K(ii) = 3.8 +/- 0.6 micromol/L, with
      respect to ATP. Second, extracellular copper causes an inhibition of the
      generation of a pH-gradient and rapid dissipation of pre-generated pH and
      catecholamine gradients. Copper chelators and the ss-amyloid peptide 1-42 were
      found to effectively prevent the inhibition. The inhibition is reversible and
      time-independent suggesting the effects of extracellular copper on H(+)-ATPase is
      direct, and not due to ROS. The physiological significance of these observations
      was shown by the demonstration that extracellular copper causes a dramatic
      perturbation of dopamine metabolism in SH-SY5Y cells. Thus, we propose that the
      direct inhibition of the vesicular H(+)-ATPase may also contribute to the
      neurotoxic effects of copper.

PMID- 17217413
TI  - Evidence for D2 receptor mediation of amphetamine-induced normalization of
      locomotion and dopamine transporter function in hypoinsulinemic rats.
AB  - Dopamine (DA) D2 receptors regulate DA transporter (DAT) activity, and mediate
      some behavioral effects of amphetamine. DA clearance and amphetamine-stimulated
      locomotion are reduced in hypoinsulinemic [streptozotocin (STZ)-treated] rats,
      and these deficits are normalized by repeated treatment with amphetamine. Here, a
      role for D2 receptors in mediating amphetamine-induced normalization of these
      parameters was investigated. One week after a saline or STZ injection (50 mg/kg),
      rats were treated with amphetamine (1.78 mg/kg), raclopride (0.056 mg/kg),
      saline, or combinations thereof, every-other-day for 8 days with locomotor
      activity measured following each treatment. Conditioned place preference (CPP)
      for amphetamine and in vivo chronoamperometry to measure DA clearance were
      carried out on days 17 and 18, respectively, after STZ or saline. Baseline
      locomotion and DA clearance were significantly reduced in STZ-treated rats
      compared with control rats. In STZ-treated rats, amphetamine treatment normalized
      DA clearance, and restored the locomotor-stimulating effects of amphetamine.
      Raclopride prevented normalization of these parameters. Amphetamine produced CPP
      in both STZ-treated and control rats; raclopride significantly attenuated
      amphetamine-induced CPP in control and not in STZ-treated rats. These results
      support a role for D2 receptors in regulating DA transporter activity, and
      further demonstrate that D2 receptors contribute to changes in sensitivity to
      amphetamine in hypoinsulinemic rats.

PMID- 17217414
TI  - Post-trauma Lipitor treatment prevents endothelial dysfunction, facilitates
      neuroprotection, and promotes locomotor recovery following spinal cord injury.
AB  - We have previously reported neuroprotection in spinal cord injury (SCI) by
      Lipitor [atorvastatin (AT)]-pre-treatment. Though informative, pre-treatment
      studies find only limited clinical application as trauma occurrence is
      unpredictable. Therefore, this study investigates the efficacy of AT treatment
      post-SCI. In a rat model of contusion-SCI resulting in complete hindlimb
      paralysis, AT treatment (5 mg/kg; gavage) was begun 2, 4, or 6 h post-SCI
      followed by a once daily dose thereafter for 6 weeks. While the placebo vehicle
      (VHC)-SCI rats showed substantial functional deficit, AT-SCI animals exhibited
      significant functional recovery. AT diminished injury-induced blood-spinal cord
      barrier (BSCB) dysfunction with significantly reduced infiltration and tumor
      necrosis factor-alpha/interleukin-1beta/inducible nitric oxide synthase
      expression at site of injury. BSCB protection in AT-SCI was attributable to
      attenuated matrix metalloproteinase-9 (MMP9) expression - a central player in
      BSCB disruption. Furthermore, endothelial MMP9 expression was found to be
      RhoA/ROCK pathway-mediated and regulated by AT through an isoprenoid-dependent
      mechanism. Attenuation of these early inflammatory events reduced secondary
      damage. Significant reduction in axonal degeneration, myelin degradation,
      gliosis, and neuronal apoptosis with resultant enhancement in tissue sparing was
      observed in AT-SCI compared with VHC-SCI. In summary, this novel report
      presenting the efficacy of post-injury AT treatment might be of critical
      therapeutic value as effective treatments are currently unavailable for SCI.

PMID- 17217415
TI  - Hydrogen peroxide triggers the proteolytic cleavage and the inactivation of
      calcineurin.
AB  - Increases in the levels of reactive oxygen species (ROS) are correlated with a
      decrease in calcineurin (CN) activity under oxidative or neuropathological
      conditions. However, the molecular mechanism underlying this ROS-mediated CN
      inactivation remains unclear. Here, we describe a mechanism for the inactivation
      of CN by hydrogen peroxide. The treatment of mouse primary cortical neuron cells
      with Abeta(1-42) peptide and hydrogen peroxide triggered the proteolytic cleavage
      of CN and decreased its enzymatic activity. In addition, hydrogen peroxide was
      found to cleave CN in different types of cells. Calcium influx was not involved
      in CN inactivation during hydrogen peroxide-mediated cleavage, but CN cleavage
      was partially blocked by chloroquine, indicating that an unidentified lysosomal
      protease is probably involved in its hydrogen peroxide-mediated cleavage.
      Treatment with hydrogen peroxide triggered CN cleavage at a specific sequence
      within its catalytic domain, and the cleaved form of CN had no enzymatic ability
      to dephosphorylate nuclear factor in activated T cells. Thus, our findings
      suggest a molecular mechanism by which hydrogen peroxide inactivates CN by
      proteolysis in ROS-related diseases.

PMID- 17217416
TI  - Tubulin cofactor B plays a role in the neuronal growth cone.
AB  - Tubulin cofactors, initially identified as alpha-, beta-tubulin folding proteins,
      are now believed to participate in the complex tubulin biogenesis and degradation
      routes, and thus to contribute to microtubule functional diversity and dynamics.
      However, a concrete role of tubulin cofactor B (TBCB) remains to be elucidated
      because this protein is not required for tubulin biogenesis, and it is apparently
      not essential for life in any of the organisms studied. In agreement with these
      data, here we show that TBCB localizes at the transition zone of the growth cones
      of growing neurites during neurogenesis where it plays a role in microtubule
      dynamics and plasticity. Gene silencing by means of small interfering RNA
      segments revealed that TBCB knockdown enhances axonal growth. In contrast, excess
      TBCB, a feature of giant axonal neuropathy, leads to microtubule
      depolymerization, growth cone retraction, and axonal damage followed by neuronal
      degeneration. These results provide an important insight into the understanding
      of the controlling mechanisms of growth cone microtubule dynamics.

PMID- 17217417
TI  - The vesicular monoamine transporter 2 contains trafficking signals in both its N
      glycosylation and C-terminal domains.
AB  - The vesicular acetylcholine transporter (VAChT) and the vesicular monoamine
      transporter (VMAT) belong to the same transporter family that packages
      acetylcholine into synaptic vesicles (SVs) and biogenic amines into large dense
      core vesicles (LDCVs) and/or SVs, respectively. These transporters share
      similarities in sequence and structure with their N- and C-terminal domains
      located in the cytoplasm. When expressed in PC12 cells, VMAT2 localizes to LDCV,
      whereas VAChT is found mainly on synaptic-like microvesicles. Previous studies
      have shown that the cytoplasmic C-terminal domain of VAChT contains signals
      targeting this transporter to SVs. However, the targeting signals for VMAT have
      not been completely elucidated. To identify signals targeting VMAT2 to LDCV, the
      subcellular localization of VMAT2-VAChT chimeras was analyzed in PC12 cells.
      Chimeras having either the N-terminal region through transmembrane domain 2 of
      VMAT2 or the C-terminal domain of VMAT2 do not traffic to LDCV efficiently. In
      contrast, chimeras having both of these regions, or the luminal glycosylated loop
      in conjunction with transmembrane domains 1 and 2 and the C-terminal domain of
      VMAT2, traffic to LDCV. Treatment of PC12 cells with 1-deoxymannojirimycin, a
      specific alpha-mannosidase I inhibitor, causes VMAT2 to localize to synaptic-like
      microvesicles. The results indicate that both mature N-linked glycosylation and
      the C-terminus are important for proper trafficking of VMAT2 and that the
      locations of trafficking signals in VMAT2 and VAChT are surprisingly different.

PMID- 17217418
TI  - Neurochemical changes in Huntington R6/2 mouse striatum detected by in vivo 1H
      NMR spectroscopy.
AB  - The neurochemical profile of the striatum of R6/2 Huntington's disease mice was
      examined at different stages of pathogenesis using in vivo(1)H NMR spectroscopy
      at 9.4 T. Between 8 and 12 weeks, R6/2 mice exhibited distinct changes in a set
      of 17 quantifiable metabolites compared with littermate controls. Concentrations
      of creatine, glycerophosphorylcholine, glutamine and glutathione increased and N
      acetylaspartate decreased at 8 weeks. By 12 weeks, concentrations of
      phosphocreatine, taurine, ascorbate, glutamate, and myo-inositol increased and
      phophorylethanolamine decreased. These metabolic changes probably reflected
      multiple processes, including compensatory processes to maintain homeostasis,
      active at different stages in the development of HD. The observed changes in
      concentrations suggested impairment of neurotransmission, neuronal integrity and
      energy demand, and increased membrane breakdown, gliosis, and osmotic and
      oxidative stress. Comparisons between metabolite concentrations from individual
      animals clearly distinguished HD transgenics from non-diseased littermates and
      identified possible markers of disease progression. Metabolic changes in R6/2
      striata were distinctly different from those observed previously in the
      quinolinic acid and 3NP models of HD. Longitudinal monitoring of changes in these
      metabolites may provide quantifiable measures of disease progression and
      treatment effects in both mouse models of HD and patients.

PMID- 17217419
TI  - Pyruvate modifies glycolytic and oxidative metabolism of rat embryonic spinal
      cord astrocyte cell lines and prevents their spontaneous transformation.
AB  - This study aimed to provide detailed data on mitochondrial respiration of normal
      astrocyte cell lines derived from rat embryonic spinal cord. Astrocytes in early
      passages (EP), cultured without pyruvate for more than 35 passages, defined here
      as late passages (LP), undergo spontaneous transformation. To study initial steps
      in cell transformation, EP data were compared with those of LP cells. LP cells
      had reduced glycolysis, fewer mitochondria and extremely low oxidative rates,
      resulting from a dysfunction of complexes I and II + III of the respiratory
      chain. Treatment of EP cells with pyruvate until they were, by definition, LP
      cultures prevented transformation of these cells. Pyruvate-treated EP cells had
      more mitochondria than normal cells but slightly lower respiratory rates. The
      increase of mitochondrial content thus appears to act as a compensatory effect to
      maintain oxidative phosphorylation in these LP 'non-transformed' cells, in which
      mitochondrial function is reduced. However, pyruvate treatment of transformed LP
      cells during additional passages did not significantly restore their oxidative
      metabolism. These data highlight changes accompanying spontaneous astrocyte
      transformation and suggest potential targets for the control of astrocyte
      proliferation and reaction to various insults to the central nervous system.

PMID- 17217420
TI  - Anti-homeostatic synaptic plasticity of glycine receptor function after chronic
      strychnine in developing cultured mouse spinal neurons.
AB  - In this study, we describe a novel form of anti-homeostatic plasticity produced
      after culturing spinal neurons with strychnine, but not bicuculline or 6-cyano-7
      nitroquinoxaline-2,3-dione (CNQX). Strychnine caused a large increase in network
      excitability, detected as spontaneous synaptic currents and calcium transients.
      The calcium transients were associated with action potential firing and
      activation of gamma-aminobutyric acid (GABA(A)) and alpha-amino-3-hydroxy-5
      methyl-4-isoxazolepropionic acid (AMPA) receptors as they were blocked by
      tetrodotoxin (TTX), bicuculline, and CNQX. After chronic blockade of glycine
      receptors (GlyRs), the frequency of synaptic transmission showed a significant
      enhancement demonstrating the phenomenon of anti-homeostatic plasticity.
      Spontaneous inhibitory glycinergic currents in treated cells showed a fourfold
      increase in frequency (from 0.55 to 2.4 Hz) and a 184% increase in average peak
      amplitude compared with control. Furthermore, the augmentation in excitability
      accelerated the decay time constant of miniature inhibitory post-synaptic
      currents. Strychnine caused an increase in GlyR current density, without changes
      in the apparent affinity. These findings support the idea of a post-synaptic
      action that partly explains the increase in synaptic transmission. This
      phenomenon of synaptic plasticity was blocked by TTX, an antibody against brain
      derived neurotrophic factor (BDNF) and K252a suggesting the involvement of the
      neuronal activity-dependent BDNF-TrkB signaling pathway. These results show that
      the properties of GlyRs are regulated by the degree of neuronal activity in the
      developing network.

PMID- 17217421
TI  - Factors influencing cell fate in the infarct rim.
AB  - In focal ischemia, the fate of penumbral cells is closely linked to the infarcted
      tissue. Because of the release of cytosolic material from damaged cells, the
      biochemical and ionic alterations within the core are dramatic. Hence, adjacent
      cells ( infarct rim) are generally exposed to these changes and may be
      deleteriously affected. To mimic such conditions in vitro, we have employed a
      slice culture system and used an ischemic solution (IS) that resembles the milieu
      in the territory of infarct rim. In contrast to normal artificial cerebral spinal
      fluid, IS is characterized by low O(2), glucose, pH; excitotoxic levels of
      glutamate; and ionic alterations. In organotypic hippocampal slice cultures, we
      examined cell injury/death using propidium iodide following exposure to IS. Our
      data show significant cell injury starting at approximately 8 h following IS
      exposure with cell injury spreading as a function of exposure duration. We
      further studied the effect of each component in the IS separately, i.e.,
      acidosis, hypoxia, ionic shifts or glutamate exitotoxicity and were able to
      isolate the contribution of each of these effectors to the IS-induced cell death.
      Our results suggest that in IS, acidosis exacerbates the potential for injury
      while ionic shifts, especially those of K(+) and Na(+), alleviate the potential
      for cell death.

PMID- 17217422
TI  - Dopaminergic toxicity associated with oral exposure to the herbicide atrazine in
      juvenile male C57BL/6 mice.
AB  - The herbicide atrazine (ATR) is a very commonly used pesticide in the United
      States. and a major ground water contaminant. It has also been recently
      implicated as a potential basal ganglia toxicant. In the present study, our
      objective was to determine the effects of ATR exposure on striatal
      neurochemistry, on the number of dopaminergic neurons in the substantia nigra
      pars compacta (SNpc), and, as a reference, in the ventral tegmental area (VTA) of
      male juvenile C57BL/6 mice. Oral exposure to ATR for 14 days dose-dependently
      decreased the levels of dopamine (DA) and its metabolites in the striatum for up
      to a week post-treatment. ATR exposure also time- and dose-dependently decreased
      the number of tyrosine hydroxylase-positive (TH+) dopaminergic neurons in both
      SNpc and VTA (with effects being slightly more prominent in SNpc), such that the
      decreases were most evident at 7 weeks post-cessation of exposure to ATR.
      Together, these data indicate that, in the juvenile male C57BL/6 mouse, the
      neurotoxic effects of ATR appear to cause transient neurochemical alterations,
      whereas the loss of TH+ neurons appears to be persistent, possibly confined to
      basal ganglia dopaminergic neurons, but not exclusive to the SNpc.

PMID- 17217423
TI  - Dynamics of immediate early gene and neuropeptide gene response to prolonged
      immobilization stress: evidence against a critical role of the termination of
      exposure to the stressor.
AB  - Stress-induced expression of immediate early genes (IEGs) appears to be transient
      even if the exposure to the stressor persists. However, there are some exceptions
      which suggest that particular characteristics of stressors can affect the
      dynamics of IEG expression. We studied in selected telencephalic, diencephalic
      and brainstem regions the mRNA levels of two clearly distinct IEGs (c-fos and
      arc) during prolonged exposure to a severe stressor such as immobilization (IMO)
      and after releasing the rats from the situation. Although regional differences
      were observed with the two IEGs, overall, c-fos mRNA levels progressively
      declined over the course of 4 h of continuous exposure to IMO, whereas arc mRNA
      levels were maintained at high levels in the brain regions that express this gene
      under stress (telencephalon). Levels of CRF hnRNA in the hypothalamus
      paraventricular nucleus only slightly declined during prolonged exposure to IMO.
      Surprisingly, termination of exposure to IMO did not modify CRF gene expression
      in the paraventricular nucleus or the pattern of IEGs expression, with the
      exception of c-fos in the lateral septum. Thus, putative signals associated to
      the termination of exposure to IMO were unable to modify either IEG expression in
      most brain areas or CRF gene expression in the paraventricular nucleus.

PMID- 17217424
TI  - Molecular mechanisms mediating pathological plasticity in Huntington's disease
      and Alzheimer's disease.
AB  - Neurodegenerative diseases such as Huntington's disease and Alzheimer's disease,
      although very different in etiology, share common degenerative processes. These
      include neuronal dysfunction, decreased neural connectivity, and disruption of
      cellular plasticity. Understanding the molecular mechanisms underlying the neural
      plasticity deficits in these devastating conditions may lead the way toward new
      therapeutic targets, both disease-specific and more generalized, which can
      ameliorate degenerative cognitive deficits. Furthermore, investigations of
      'pathological plasticity' in these diseases lend insight into normal brain
      function. This review will present evidence for altered plasticity in
      Huntington's and Alzheimer's diseases, relate these findings to symptomatology,
      and review possible causes and commonalities.

PMID- 17217425
TI  - Dendritic cell biology during malaria.
AB  - Malaria is an infectious disease that causes serious morbidity and mortality
      worldwide. The disease is associated with a variety of clinical syndromes ranging
      from asymptomatic to lethal infections involving anaemia, organ failure,
      pulmonary and cerebral disease. The molecular and cellular factors responsible
      for the differences in disease severity are poorly understood but parasite
      specific immune responses are thought to play a critical role in pathogenesis.
      Dendritic cells have an essential role in linking innate and adaptive immune
      responses and here we review their role in the context of malaria.

PMID- 17217426
TI  - The 65 kDa mannoprotein gene of Candida albicans encodes a putative beta
      glucanase adhesin required for hyphal morphogenesis and experimental
      pathogenicity.
AB  - Mannoproteins are fungal cell wall components which play a main role in host
      parasite relationship. Camp65p is a putative beta-glucanase mannoprotein of 65
      kDa which has been characterized as a main target of human immune response
      against Candida albicans. However, nothing is known about its specific
      contribution to the biology and virulence of this fungus. We constructed CAMP65
      knock-out mutants including null camp65/camp65 and CAMP65/camp65 heterozygous
      strains. The null strains had the same growth rate and morphology under yeast
      form as the wild-type strain but they were severely affected in hyphal
      morphogenesis both in vitro and in vivo. Hyphae formation was restored in
      revertant strains. The null mutants lost adherence to the plastic, and this was
      in keeping with the strong inhibition of fungal cell adherence to plastic exerted
      by anti-Camp65p antibodies. The null mutants were also significantly less
      virulent than the parental strains, and this loss of virulence was observed both
      in systemic and in mucosal C. albicans infection models. Nonetheless, the
      virulence in both infectious models was regained by the CAMP65 revertants. Thus,
      CAMP65 of C. albicans encodes a putative beta-glucanase, mannoprotein adhesin,
      which has a dual role (hyphal cell wall construction and virulence), accounting
      for the particular relevance of host immune response against this mannoprotein.

PMID- 17217427
TI  - Measles virus nucleocapsid transport to the plasma membrane requires stable
      expression and surface accumulation of the viral matrix protein.
AB  - In measles virus (MV)-infected cells the matrix (M) protein plays a key role in
      virus assembly and budding processes at the plasma membrane because it mediates
      the contact between the viral surface glycoproteins and the nucleocapsids. By
      exchanging valine 101, a highly conserved residue among all paramyxoviral M
      proteins, we generated a recombinant MV (rMV) from cloned cDNA encoding for a M
      protein with an increased intracellular turnover. The mutant rMV was barely
      released from the infected cells. This assembly defect was not due to a defective
      M binding to other matrix- or nucleoproteins, but could rather be assigned to a
      reduced ability to associate with cellular membranes, and more importantly, to a
      defective accumulation at the plasma membrane which was accompanied by the
      deficient transport of nucleocapsids to the cell surface. Thus, we show for the
      first time that M stability and accumulation at intracellular membranes is a
      prerequisite for M and nucleocapsid co-transport to the plasma membrane and for
      subsequent virus assembly and budding processes.

PMID- 17217428
TI  - Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at
      human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site.
AB  - Lipopolysaccharides containing underacylated lipid A structures exhibit reduced
      abilities to activate the human (h) Toll-like receptor 4 (TLR4) signalling
      pathway and function as potent antagonists against lipopolysaccharides bearing
      canonical lipid A structures. Expression of underacylated lipopolysaccharides has
      emerged as a novel mechanism utilized by microbial pathogens to modulate host
      innate immune responses. Notably, antagonistic lipopolysaccharides are prime
      therapeutic candidates for combating Gram negative bacterial sepsis. Penta
      acylated msbB and tetra-acylated Porphyromonas gingivalis lipopolysaccharides
      functionally antagonize hexa-acylated Escherichia coli lipopolysaccharide
      dependent activation of hTLR4 through the coreceptor, hMD-2. Here, the molecular
      mechanism by which these antagonistic lipopolysaccharides act at hMD-2 is
      examined. We present evidence that both msbB and P. gingivalis
      lipopolysaccharides are capable of direct binding to hMD-2. These antagonistic
      lipopolysaccharides can utilize at least two distinct mechanisms to block E. coli
      lipopolysaccharide-dependent activation of hTLR4. The main mechanism consists of
      direct competition between the antagonistic lipopolysaccharides and E. coli
      lipopolysaccharide for the same binding site on hMD-2, while the secondary
      mechanism involves the ability of antagonistic lipopolysaccharide-hMD-2 complexes
      to inhibit E. coli lipopolysaccharide-hMD-2 complexes function at hTLR4. It is
      also shown that both hTLR4 and hMD-2 contribute to the species-specific
      recognition of msbB and P. gingivalis lipopolysaccharides as antagonists at the
      hTLR4 complex.

PMID- 17217429
TI  - Global analysis of community-associated methicillin-resistant Staphylococcus
      aureus exoproteins reveals molecules produced in vitro and during infection.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a
      threat to human health worldwide. Although progress has been made, mechanisms of
      CA-MRSA pathogenesis are poorly understood and a comprehensive analysis of CA
      MRSA exoproteins has not been conducted. To address that deficiency, we used
      proteomics to identify exoproteins made by MW2 (USA400) and LAC (USA300) during
      growth in vitro. Two hundred and fifty unique exoproteins were identified by 2
      dimensional gel electrophoresis coupled with automated direct infusion-tandem
      mass spectrometry (ADI-MS/MS) analysis. Eleven known virulence-related
      exoproteins differed in abundance between the strains, including alpha-haemolysin
      (Hla), collagen adhesin (Cna), staphylokinase (Sak), coagulase (Coa), lipase
      (Lip), enterotoxin C3 (Sec3), enterotoxin Q (Seq), V8 protease (SspA) and
      cysteine protease (SspB). Mice infected with MW2 or LAC produced antibodies
      specific for known or putative virulence factors, such as autolysin (Atl), Cna,
      Ear, ferritin (Ftn), Lip, 1-phosphatidylinositol phosphodiesterase (Plc), Sak,
      Sec3 and SspB, indicating the exoproteins are made during infection in vivo. We
      used confocal microscopy to demonstrate aureolysin (Aur), Hla, SspA and SspB are
      produced following phagocytosis by human neutrophils, thereby linking exoprotein
      production in vitro with that during host-pathogen interaction. We conclude that
      the exoproteins identified herein likely account in part for the success of CA
      MRSA as a human pathogen.

PMID- 17217430
TI  - Capsule and D-alanylated lipoteichoic acids protect Streptococcus pneumoniae
      against neutrophil extracellular traps.
AB  - Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide.
      Pneumococci can counteract the action of neutrophils with an antiphagocytic
      capsule and through electrochemical repulsion of antimicrobial peptides via
      addition of positive charge to the surface. Pneumococci are captured, but not
      killed in neutrophil extracellular traps (NETs). Here, we study the role of the
      polysaccharide capsule and lipoteichoic acid (LTA) modification on pneumococcal
      interaction with NETs. Expression of capsule (serotypes 1, 2, 4 and 9V)
      significantly reduced trapping by NETs, but was not required for resistance to
      NET-mediated killing. Pneumococci contain a dlt operon that mediates the
      incorporation of d-alanine residues into LTAs, thereby introducing positive
      charge. Genetic inactivation of dltA in non-encapsulated pneumococci rendered the
      organism sensitive to killing by antimicrobial components present in NETs.
      However, the encapsulated dltA mutant remained resistant to NET-mediated killing
      in vitro. Nevertheless, in a murine model of pneumococcal pneumonia, the
      encapsulated dltA-mutant strain was outcompeted by the wild-type upon invasion
      into the lungs and bloodstream. This suggests a non-redundant role for LTA
      alanylation in pneumococcal virulence at the early stage of invasive disease when
      capsule expression has been shown to be low.

PMID- 17217431
TI  - The Helicobacter pylori CagA protein disrupts matrix adhesion of gastric
      epithelial cells by dephosphorylation of vinculin.
AB  - Helicobacter pylori colonizes the human stomach, contributing to or causing
      several diseases. Translocation of the CagA bacterial protein into gastric
      epithelial cells has been linked to an increased risk of peptic ulcer disease and
      gastric carcinoma. Upon translocation, CagA is tyrosine phosphorylated by Src
      family kinases (SFKs), which themselves become inactivated via a negative
      feedback loop. Here, we show that tyrosine-phosphorylated CagA disrupts adhesion
      of AGS cells to the extracellular matrix. Owing to the inactivation of c-Src via
      CagA interaction, vinculin is dephosphorylated at tyrosine residues, 100 and
      1065, by corresponding phosphatases. Vinculin dephosphorylation disturbs the
      interaction and recruitment of the actin-related protein 2/3 (Arp2/3) complex by
      p34Arc, resulting in a reduction of focal adhesion complexes. These defects can
      be mimicked by downregulating vinculin using RNA interference in non-infected
      cells. Tyrosine dephosphorylation of vinculin results in severe cellular
      deficiencies in cell-matrix adhesion, cell spreading and wound repair. We
      hypothesize that CagA-mediated inactivation of vinculin is a key step in the
      mechanism by which H. pylori induces damage to the gastric epithelium and
      represents an important step in disease development.

PMID- 17217432
TI  - Microdissection of the cytokine milieu of pulmonary granulomas from tuberculous
      guinea pigs.
AB  - Levels of IL-12p40, TNFalpha, TGFbeta, IFNgamma and IL-10 mRNA were assessed by
      laser capture microdissection followed by quantitative real-time PCR in the
      pulmonary granulomas of unimmunized and BCG-vaccinated guinea pigs infected by
      aerosol with virulent Mycobacterium tuberculosis. Lesions microdissected from
      unimmunized guinea pigs were overwhelmed by the pro-inflammatory TNFalpha mRNA at
      both 3 and 6 weeks post infection, indicating the struggle to control the
      mounting infection. The cytokine profile of granulomas from vaccinated guinea
      pigs shifted from type 1 cytokine mRNA (IFNgamma and IL-12p40) at 3 weeks to a
      predominantly anti-inflammatory environment (TGFbeta mRNA) at 6 weeks. The
      relative proportions of cytokine mRNA transcripts in the periphery of the
      granuloma were different from the centre, reflecting differences in cell
      composition and architecture. Moreover, analysis of the individual lung lobes at
      6 weeks post infection suggests that heterogeneity exists in the cytokine profile
      between the lobes of the lung.

PMID- 17217433
TI  - Immunosuppression for dual kidney transplantation with marginal organs: the old
      is better yet.
AB  - Immunosuppressive protocols in dual kidney transplantation (DKT) are based on
      calcineurin inhibitors (CNI). We wonder whether a CNI-free immunosuppression can
      improve outcome in older patients receiving a DKT with marginal donor organs.
      Thirty-six were treated with CsA, MMF and prednisone (CsA group) and 42 with
      rATG, SRL, MMF and prednisone (SRL group). Incidence of delayed graft function
      and acute rejection was 44% and 11% in the CsA group, and 40% and 8% in the SRL
      group. CMV infection incidence was low in both protocols. Three-year patient
      survival was 89% in the CsA and 76% in the SRL group. One- and 3-year graft
      survival after censoring for dead with a functioning allograft was 94.2% and 94%
      in CsA and 95% and 90% in SRL, respectively. Renal function was similar in both
      groups whereas proteinuria was higher in the SRL group. Uninephrectomy due to
      graft thrombosis or urinary-related complications was numerically higher in the
      SRL (21%) than in the CsA group (8%) (p = 0.13) and it was associated with renal
      failure and proteinuria. In DKT, a new induction immunosuppressive protocol based
      on rATG, SRL, MMF and prednisone does not offer any advantage in comparison to
      the old CsA, MMF and prednisone.

PMID- 17217434
TI  - Familial hypocalciuric hypercalcemia in the donor and recipient of a living
      related donor kidney transplant.
AB  - Familial hypocalciuric hypercalcemia (FHH) is caused by heterozygous inactivation
      of the calcium-sensing receptor, which is notably expressed in parathyroid and
      kidney. FHH is characterized by asymptomatic hypercalcemia and hypophosphatemia
      and confers minimal, if any, morbidity. Renal transplantation in patients with
      FHH has not been described previously. This report describes a patient with FHH
      who developed end-stage renal disease from another cause and subsequently
      received a living related donor kidney transplant from her FHH-affected daughter.
      The excellent posttransplant clinical course of both recipient and donor is
      emphasized.

PMID- 17217435
TI  - Genetic regulation of rejection and survival following human lung transplantation
      by the innate immune receptor CD14.
AB  - We have developed the hypothesis that genetic polymorphisms which alter the
      expression or function of innate immune receptors contribute to the marked
      interindividual differences in the onset and severity of lung transplant
      rejection. In this analysis, we considered the effects of a common promotor
      polymorphism of the lipopolysaccharide receptor CD14 associated with increased
      transcriptional activity upon the development of posttransplant rejection and
      graft survival. Genotyping was performed in 226 lung transplant recipients well
      characterized with regards to clinical outcomes. An earlier onset of acute
      rejection, bronchiolitis obliterans syndrome (BOS) and worse posttransplant graft
      survival due to greater BOS related deaths was evident in patients with the CD14 
      159 TT genotype (TT). The adverse effect upon graft survival of the TT genotype
      remained significant in a multivariate Cox model (Hazard Ratio 1.65, 95% CI, 1.03
      2.64, p-value = 0.04) after adjusting for other important covariates.
      Furthermore, TT patients have significantly greater sCD14, TNF-alpha and IFN
      gamma in the peripheral blood implying a heightened state of innate immune
      activation drives the development of increased post-transplant rejection.
      Inhibition of innate immune activation through CD14 represents a novel and
      potentially important therapeutic target to prevent post-transplant rejection and
      improve outcomes after human lung transplantation.

PMID- 17217436
TI  - Immunogenicity of pneumococcal vaccine in renal transplant recipients--three year
      follow-up of a randomized trial.
AB  - Routine pneumococcal vaccination is recommended at regular intervals
      posttransplant. However, there is limited data on durability of vaccine response
      and the impact of vaccine type on antibody persistence. We determined the
      durability of response for patients enrolled in a randomized trial of conjugate
      (PCV7) versus polysaccharide (PPV23) pneumococcal vaccination. Response was
      defined as a twofold increase from baseline and a titer > or =0.35 microg/mL
      using a pneumococcal ELISA for seven serotypes (measured at 8 weeks and 3 years).
      Forty-seven patients were evaluated and had received either PPV23 (n = 24) or
      PCV7 (n = 23). Response rates and geometric mean titers varied by serotype but
      declined significantly at 3-years for 6 of 7 serotypes (p < 0.001). No
      significant difference in durability was found in patients that had received
      PPV23 versus PCV7. Compared to the 8-week response, 20.6% fewer patients had a
      response to at least one serotype by 3 years. The largest relative declines were
      seen for serotype 4 (response dropped from 40.4% at 8 weeks to 17.0% at 3 years)
      and serotype 9V (44.7% dropping to 21.3%). The only factor predictive of response
      durability was a strong multiserotype initial response (p < 0.001). In
      conclusion, vaccine responses decline significantly by 3 years and conjugate
      vaccine does not improve the durability of response.

PMID- 17217437
TI  - Female liver transplant recipients with the same GFR as male recipients have
      lower MELD scores--a systematic bias.
AB  - Women have lower glomerular filtration (GFR) than men for the same serum
      creatinine (Cr) value, not accounted for in model for end-stage liver disease
      (MELD). We compare male/female Cr, GFR (using MDRD formula) and respective MELD
      scores in 403 Cr measurements using standard (sCr), O'Leary modified (mCr) and
      Compensated (cCr) Jaffe and Enzymatic (eCr) in 158 liver disease patients, mCr in
      208 liver transplantation (LT) candidates, and EDTA-Cr(51)-GFR in 38 other
      candidates for LT; considering each female as male, a 'corrected' Cr was derived.
      MELD scores were calculated for measured and "corrected" Cr in females. Median Cr
      and GFR in females were lower than males (p < 0.05). Both MDRD and EDTA-Cr(51)
      GFR were lower in females than males, despite lower Cr values. In females, each
      MELD score was lower than the corresponding MELD-corrected Cr (p < 0.001) with >
      or =three-point difference in liver disease patients: 25%[sCr]; 23%[mCr];
      11%[eCr]; and 14%[cCr]. In 65% of female LT candidates, two- or three-point
      difference was found. Females with liver disease have lower GFR than males for
      the same Cr value; correcting Cr increases MELD score by two or three points in
      65% of female LT candidates. MELD score adjustment in females would ensure equal
      LT priority by gender.

PMID- 17217438
TI  - Urinary albumin excretion and the risk of graft loss and death in proteinuric and
      non-proteinuric renal transplant recipients.
AB  - BACKGROUND: Microalbuminuria and macroalbuminuria constitute risk factors for
      ESRD and death in non-transplanted populations. Whether microalbuminuria
      (especially in non-proteinuric patients) and macroalbuminuria constitute risk
      factors for graft loss and death is presently unknown in renal transplantation.
      METHODS: We retrospectively assessed the association between urinary albumin
      excretion (UAE) and ESRD and death in renal transplantation. RESULTS: UAE was
      measured in 616 (397 proteinuric; 219 non-proteinuric patients) renal transplant
      recipients. They were grafted for 62 months (range: 6-192). During the 40 months
      (3.7-99) thereafter, 31 patients underwent dialysis and 32 died. Microalbuminuria
      (vs. normoalbuminuria) and macroalbuminuria (vs. microalbuminuria) were powerful
      risk factors for graft loss [OR: 14.25 (2.88-52.3) and 16.41 (7.46-36.0),
      respectively, both p < 0.0001], even after adjustments on renal function and
      diabetes. Among the 219 non-proteinuric patients, microalbuminuria (vs.
      normoalbuminuria) was a significant risk factor for graft loss [OR: 23.09 (1.93
      276.4), p = 0.0132]. Both microalbuminuria (vs. normoalbuminuria) [OR: 5.55 (2.43
      12.66), p < 0.0001] and macroalbuminuria (vs. microalbuminuria) [OR: 4.12 (1.65
      10.29), p = 0.0024] were predictive of death. CONCLUSIONS: Microalbuminuria and
      macroalbuminuria are powerful independent predictors of ESRD and death.
      Microalbuminuria is a risk factor for graft loss even in non-proteinuric
      patients. UAE provides additional information on renal and patient prognosis as
      compared to proteinuria and renal function.

PMID- 17217439
TI  - Improved outcomes of renal transplantation from cardiac death donors: a 30-year
      single center experience.
AB  - Outcomes of renal transplantation from donation after cardiac death (DCD) donors
      over 30 years were analyzed. Between 1975 and 2004, 256 renal transplantations
      from DCD donors were performed. The recipients were divided into four groups
      according to a time period as follows: 1975-1979 (Group 1; n = 18), 1980-1989
      (Group 2; n = 81), 1990-1999 (Group 3; n = 84) and 2000-2004 (Group 4; n = 73).
      Of the 256 transplanted kidneys from DCD donors, 38 (15%) functioned immediately
      after transplantation. The incidence of delayed graft function (DGF) was 72%.
      Warm ischemic time and total ischemic time were 7.4 +/- 9.4 min and 11.9 +/- 5.6
      h, respectively. The overall graft survival rates at 1, 5 and 10 years were 80%,
      72% and 53%, respectively. Graft survival rates in each group have continually
      improved over time (5-year graft survival; 23% vs. 64% vs. 74% vs. 91%,
      respectively). However, there was no significant difference in graft survival
      rates between the groups of patients who survived with a functioning graft for
      more than 1 year. A multivariate Cox regression analysis showed acute rejection
      and donor age to be independently associated with graft outcome. DCD donors are a
      valuable source of kidneys for transplantation with promising long-term outcomes.

PMID- 17217440
TI  - Liver transplantation from deceased donors serologically positive for Chagas
      disease.
AB  - The high mortality rates among patients waiting for liver transplantation has
      motivated the use of "marginal livers", among which are included livers from
      deceased donors serologically positive for Chagas disease (CD). The present work
      describes the outcome of orthotopic liver transplantation in six patients with
      severe liver disease (Child Pugh C), with livers from donors serologically
      positive for CD. Transplantations were performed from November 2000 to January
      2005, and the patients received prophylactic treatment with benznidazole for 60
      days, as a recommended by the Brazilian Consensus in Chagas Disease. The
      transplantation procedures presented no technical problems, and all the patients
      were discharged from hospital. Five of them did not present side effects
      demanding interruption of the prophylactic treatment. Four of the patients were
      clinically well over 1 year after transplantation (mean follow-up of 42.1
      months), with negative serological results for CD. Two patients died, one of them
      6 months post surgery of sepsis due to biliary complication and other one due to
      pulmonary (tuberculosis) complications. They were both serologically negative for
      CD. These results suggest that liver transplantation from CD donors, followed by
      benznidazole prophylactic treatment, is an important therapeutic alternative for
      severe liver disease.

PMID- 17217441
TI  - Intravenous iloprost: a new therapeutic option for patients with post-transplant
      distal limb syndrome (PTDLS).
AB  - The purpose of this study was to investigate the application of intravenous
      iloprost as a novel therapy for the treatment of post-transplant distal limb
      syndrome (PTDLS). PTDLS is a benign but disabling complication in the first year
      after renal transplantation. It is characterized by bilateral, often
      incapacitating pain in the feet and or knees on motion and a significant rise in
      alkaline phosphatase levels on laboratory evaluation. On MRI, bone marrow edema
      of the affected bone regions can be demonstrated. PTDLS differs from steroid
      induced osteonecrosis of the hip in terms of localization, an average cumulative
      steroid dosage within expected limits, and a benign outcome, as PTDLS does not
      progress to overt cell necrosis. From August 2003 to April 2005 we treated 10
      patients with MRI-proven diagnosis of PTDLS following a standardized regimen of
      intravenous iloprost over 5 days. Iloprost led to prompt pain relief measured on
      a visual analogous scale (VAS) ranging from 1 to 10 (5.6 +/- 1.5 before vs. 2.1
      +/- 1.3 after treatment, p = 0.0004). PTDLS represents a benign but disabling
      complication following renal transplantation. Intravenous iloprost might be a
      promising therapeutic concept leading to a quick relief of symptoms without
      relevant side effects.

PMID- 17217442
TI  - One-year results with extended-release tacrolimus/MMF, tacrolimus/MMF and
      cyclosporine/MMF in de novo kidney transplant recipients.
AB  - Once-daily tacrolimus extended-release formulation (Prograf XL, formerly referred
      to as MR or MR4) was compared with the twice-a-day tacrolimus formulation (TAC)
      and cyclosporine microemulsion (CsA), all administered in combination with
      mycophenolate mofetil (MMF), corticosteroids and basiliximab induction, in a
      phase 3, randomized (1:1:1), open-label trial in 638 de novo kidney transplant
      recipients. In combination with MMF and corticosteroids, XL had an efficacy
      profile comparable to TAC and CsA. XL/MMF and TAC/MMF were statistically
      noninferior at 1-year posttransplantation to CsA/MMF for the primary efficacy
      endpoint, efficacy failure (death, graft loss, biopsy-confirmed acute rejection
      (BCAR) or lost to follow-up). One-year patient and graft survival were 98.6% and
      96.7% in the XL/MMF group, 95.7% and 92.9% in TAC/MMF group and 97.6% and 95.7%
      in CsA/MMF group. The safety profile of XL in comparison with CsA was similar to
      that observed with TAC in this study and consistent with previously published
      reports of TAC in comparison with CsA. The results support the safety and
      efficacy of tacrolimus in combination with MMF, corticosteroids and basiliximab
      induction, as well as XL as a safe and effective once-daily dosing alternative.

PMID- 17217443
TI  - Functional compartmentalization following induction of long-term graft survival
      with pregraft donor-specific transfusion.
AB  - Long-term survival is achieved in rat recipients by pre-graft donor-specific
      blood transfusion. We characterized the immune compartments in long-term
      survivors and analyzed them for capacity to transfer tolerance and protect
      against chronic rejection. Splenocytes and spleen T cells from treated recipients
      transferred long-term graft survival to 100% of secondary recipients. In
      contrast, blood transferred graft survival to only 50% of recipients whereas
      blood T cells had no effect. An unaltered TCR repertoire, an increase in
      suppressive CD4+CD25+ T cells, a decrease in antidonor T-cell proliferative
      response and normal perforin-granzyme levels were the hallmarks of the spleen T
      cells. Blood T cells were characterized by a strongly altered CD8+ repertoire,
      normal CD4+CD25+ T cell number with unchanged antidonor T-cell proliferative
      response, an activated T-cell phenotype and an increase in perforin-granzyme
      levels. However, following the transfer of blood or spleen cells into secondary
      recipients, all grafts displayed chronic rejection. These findings provide
      evidence that distinct compartments play critical roles in DST recipients.
      Regulatory cells do not accumulate in blood, which appears to be a reservoir for
      cytotoxic T cells. Spleen T cells, which display a regulatory-like profile and
      transfer graft survival, are not able to prevent chronic rejection.

PMID- 17217444
TI  - The relationship between dosing of alosetron and discontinuation patterns
      reported by patients participating in a follow-up programme.
AB  - BACKGROUND: Alosetron was reintroduced for treatment of irritable bowel syndrome
      with a risk management programme in November 2002. Recommended starting dosage
      was 1 mg/day for 4 weeks. If symptoms remained uncontrolled, dosage could be
      changed to 2 mg/day. AIM: To describe alosetron dosages and associated patient
      characteristics from the Lotronex follow-up survey programme. METHODS: Patients
      reported dosages of alosetron at start and regular follow-up intervals. Analyses
      were limited to patients with the potential to have at least 1 year of follow-up
      (enrolled between 9 December 2002 and 31 December 2003). RESULTS: At baseline,
      75% of 2817 respondents reported starting on 1 mg/day, 17% on 2 mg/day and 8% on
      other doses. Adherence to recommended starting dosage did not vary by status at
      end of follow-up, previous alosetron experience or age. At last reported dose,
      50% of respondents were using 1 mg/day; 29% were using 2 mg/day. Discontinuation
      was not related to baseline doses. Longer times to discontinuation were
      associated with previous use, symptoms for more than 6 months and dose change
      throughout follow-up. CONCLUSIONS: High adherence to recommended dosing at
      baseline and follow-up suggests that the risk management programme is encouraging
      safe use of alosetron, including adherence to dosing recommendations.

PMID- 17217445
TI  - Change over time of bowel habit in irritable bowel syndrome: a prospective,
      observational, 1-year follow-up study (RITMO study).
AB  - BACKGROUND: Evolution of bowel habit in irritable bowel syndrome (IBS) is not
      well known. AIM: To evaluate the change over time of bowel habit in IBS patients
      followed-up during 1 year. METHODS: Five hundred and seventeen patients with IBS
      were prospectively included in an observational study with five evaluations over
      a 1-year period. Symptoms were recorded daily in diary cards during four 4-week
      periods along the study. Bristol Stool Scale (BSS) was used to define bowel
      habit. RESULTS: Four-hundred patients completed the study. Rome II showed low
      moderate agreement (42%) with BSS to define bowel habit. Frequency of
      constipation and diarrhoea showed little changes throughout the study. Over 50%
      of the patients had the same bowel habit when each diary was compared with the
      next one. A third of patients maintained the same habit throughout the study.
      Most changes occurred from/to mixed or unsubtyped IBS. Only 14% of cases changed
      from constipation to diarrhoea or vice versa. This change was associated to
      female gender (OR: 2.65). CONCLUSIONS: The frequency of constipation and
      diarrhoea remains relatively stable over time. Changes in IBS subtypes are
      common, but changes between constipation and diarrhoea are rare. Alternating IBS
      is more frequent in women.

PMID- 17217448
TI  - Review article: glucagon-like peptide 2--current applications and future
      directions.
AB  - BACKGROUND: Glucagon-like peptide 2 (GLP-2) is an important peptide growth factor
      secreted from the human intestine. The trophic properties of GLP-2 are very
      specific to the gut where it is pivotal in the regulation of mucosal morphology,
      function and integrity. AIMS: This review details the current understanding of
      the molecular biology of GLP-2, its mechanisms of action and physiological
      properties. A major focus is the discussion of recent clinical data evaluating
      the use of GLP-2 as a therapeutic agent. METHODS: Relevant articles were
      identified using Medline searches and from the reference lists of key papers.
      RESULTS AND CONCLUSIONS: In the treatment of short bowel syndrome, GLP-2 has been
      shown to be highly effective in improving fluid absorption. In Crohn's disease,
      GLP-2 is superior to placebo in the induction of remission. Early data also
      suggest that the effects of GLP-2 on bone metabolism can provide a new treatment
      approach for patients with osteoporosis. In the future, the positive effects of
      GLP-2 on intestinal barrier function, splanchnic perfusion and mucosal healing
      could be utilized to expand its therapeutic application to other causes of
      intestinal injury. However, important safety aspects need to be considered when
      using this potent growth-promoting agent for a long term.

PMID- 17217449
TI  - Risk of low-dose aspirin: emphasis on outliers undermines the credibility of the
      conclusions.

PMID- 17217450
TI  - Neurokinin-1 receptor antagonism in a human model of visceral hypersensitivity.
AB  - BACKGROUND: Substance P acting via the neurokinin-1 receptor is involved in the
      development of hyperalgesia, although studies using neurokinin-1 receptor
      antagonists (NK-1RA) in human somatic pain have been disappointing. AIM: To
      evaluate whether Substance P is involved in the development of human visceral
      pain/hyperalgesia using a selective NK-1RA. METHODS: Using a validated human
      model of acid-induced oesophageal allodynia, pain thresholds to electrical
      stimulation (mA) were measured in the proximal oesophagus and the foot (somatic
      control), pre- and for 4 h postdistal oesophageal acid in 14 healthy subjects,
      using a double-blind, randomized, two-period, crossover study. Measurements were
      taken on the third day of dosing with either an oral NK-1RA or matching placebo,
      with 2 weeks washout between periods. RESULTS: Baseline pain threshold did not
      differ between treatments (proximal oesophagus 37 +/- 7.4 mA NK-1RA vs. 38 +/-
      10.1 placebo P = 0.81, foot 40 +/- 15 mA NK-1RA vs. 38 +/- 14 placebo P = 0.68).
      NK-1RA did not attenuate the reduction in pain threshold in the proximal
      oesophagus postacid infusion (AUC-394 +/- 279 NK-1RA vs. -262 +/- 397 placebo P =
      0.54). CONCLUSIONS: The lack of effect of NK-1RA on oesophageal pain threshold in
      our model does not support a role for Substance P in the development of acid
      induced oesophageal allodynia.

PMID- 17217451
TI  - Pre-endoscopic PPI therapy reduces recurrent adverse outcomes in acute non
      variceal upper gastrointestinal bleeding.

PMID- 17217452
TI  - Perioperative acute upper gastrointestinal haemorrhage in older patients with hip
      fracture: incidence, risk factors and prevention.
AB  - BACKGROUND: No specific preventive strategy exists for acute gastrointestinal
      haemorrhage in hip fracture patients. AIMS: To determine the effectiveness of
      prophylactic use of proton pump inhibitors in patients with risk factors for
      acute gastrointestinal haemorrhage. METHODS: Prospective two-stage study of 822
      consecutive older (> or =60 years) hip fracture patients. RESULTS: Acute
      gastrointestinal haemorrhage occurred in 16 (3.9%) of 407 patients and was
      associated with increased length of hospital stay (28.7 vs. 15.9; P = 0.0027) and
      mortality (18.8% vs. 4.3%; P = 0.043). Multiple analysis identified five
      independent risk factors for acute gastrointestinal haemorrhage: pre-existing
      peptic ulcer (OR 4.3; P = 0.043), current smoking (OR 3.1; P = 0.023), post
      operative use of an antiplatelet agent (OR 6.5; P = 0.046), post-operative use of
      non-steroidal anti-inflammatory drug/cyclo-oxygenase-2 inhibitor (OR 4.9; P =
      0.06) and blood group O (OR 1.7; P = 0.046). These risk factors were highly
      sensitive and had a negative predictive value of 99.8%. Prophylactic use of
      proton pump inhibitors in patients with risk factor for acute gastrointestinal
      haemorrhage significantly reduced the incidence of this complication (0.72% in
      treated patients vs. 13.4% in untreated; P < 0.001); the number needed to treat
      was 7.9. Conclusions In older hip fracture patients perioperative acute
      gastrointestinal haemorrhage occurs in 3.9% and is associated with poor outcome.
      Preventive proton pump inhibitor therapy in patients at risk of acute
      gastrointestinal haemorrhage is effective and safe.

PMID- 17217453
TI  - Review article: fructose malabsorption and the bigger picture.
AB  - Fructose is found widely in the diet as a free hexose, as the disaccharide,
      sucrose and in a polymerized form (fructans). Free fructose has limited
      absorption in the small intestine, with up to one half of the population unable
      to completely absorb a load of 25 g. Average daily intake of fructose varies from
      11 to 54 g around the world. Fructans are not hydrolysed or absorbed in the small
      intestine. The physiological consequences of their malabsorption include
      increasing osmotic load, providing substrate for rapid bacterial fermentation,
      changing gastrointestinal motility, promoting mucosal biofilm and altering the
      profile of bacteria. These effects are additive with other short-chain poorly
      absorbed carbohydrates such as sorbitol. The clinical significance of these
      events depends upon the response of the bowel to such changes; they have a higher
      chance of inducing symptoms in patients with functional gut disorders than
      asymptomatic subjects. Restricting dietary intake of free fructose and/or
      fructans may have durable symptomatic benefits in a high proportion of patients
      with functional gut disorders, but high quality evidence is lacking. It is
      proposed that confusion over the clinical relevance of fructose malabsorption may
      be reduced by regarding it not as an abnormality but as a physiological process
      offering an opportunity to improve functional gastrointestinal symptoms by
      dietary change.

PMID- 17217454
TI  - Review article: biological activity markers in inflammatory bowel disease.
AB  - BACKGROUND: Traditionally, inflammatory bowel disease activity is assessed by
      clinical activity indices that measure clinical symptoms and endoscopic indices
      that measure endoscopic inflammation. Biological markers are a non-invasive way
      of objectively measuring inflammation and can play an adjunctive or primary role
      in the assessment of disease activity. AIM: To review the data on biological
      markers for assessment of disease activity and prediction of relapse in
      inflammatory bowel disease. METHODS: To collect relevant articles, a PubMed
      search was performed from 1980 to 2006 using following search terms in
      combination: inflammatory bowel disease, biomarkers, inflammation, disease
      activity, relapse, acute phase reactants cytokines, interleukins, adhesion
      molecules, integrins, calprotectin and lactoferrin. RESULTS: Biological activity
      markers can be classified into serological, faecal and miscellaneous categories.
      Acute phase reactants levels correlate with disease activity and some can be used
      to help predict relapse. Cytokines and adhesion molecules are elevated in active
      disease inconsistently. Faecal markers are useful in assessment of disease
      activity and relapse. CONCLUSIONS: Acute phase reactants and faecal markers are
      useful to assess the disease activity in clinical practice. More data are
      required on cytokines and adhesion molecules. C-reactive protein, erythrocyte
      sedimentation rate, interleukins and faecal markers may be useful in predicting a
      relapse.

PMID- 17217455
TI  - Review article: medical management of the liver transplant recipient - a primer
      for non-transplant doctors.
AB  - BACKGROUND: Survival 10 years after orthotopic liver transplantation now
      approaches 65%. Consequently, community doctors must manage the metabolic and
      neoplastic complications of orthotopic liver transplantation in an ageing
      population. AIMS: To review common sources of morbidity and mortality in long
      term orthotopic liver transplantation recipients, and to make evidence-based
      recommendations regarding their management. METHODS: Pertinent studies and
      reviews were identified by literature search through PubMed. Where evidence-based
      recommendations could not be gleaned from the literature, expert opinion was
      obtained from syllabi of national meetings. RESULTS: The two most common causes
      of morbidity and mortality in orthotopic liver transplantation recipients are
      atherosclerotic vascular disease and de novo malignancy. The pathogenesis of many
      complications begins before orthotopic liver transplantation, and many are
      potentially modifiable. Most complications, however, can be directly ascribed to
      immunosuppressive agents. Despite improvements in our understanding of the
      pathogenesis and epidemiology of the metabolic and neoplastic complications of
      orthotopic liver transplantation, remarkably few randomized-controlled studies
      exist to define their optimal management. CONCLUSIONS: Orthotopic liver
      transplantation recipients experience and succumb to the same afflictions of old
      age as non-transplant patients, but with greater frequency and at an earlier age.
      Most recommendations regarding surveillance for, and treatment of, medical
      complications of orthotopic liver transplantation remain based upon expert
      opinion rather than evidence-based medicine.

PMID- 17217456
TI  - A lysine-rich arabinogalactan protein in Arabidopsis is essential for plant
      growth and development, including cell division and expansion.
AB  - Arabinogalactan proteins (AGPs), a family of hydroxyproline-rich glycoproteins,
      occur throughout the plant kingdom. The lysine-rich classical AGP subfamily in
      Arabidopsis consists of three members, AtAGP17, 18 and 19. In this study, AtAGP19
      was examined in terms of its gene expression pattern and function. AtAGP19 mRNA
      was abundant in stems, with moderate levels in flowers and roots and low levels
      in leaves. AtAGP19 promoter-controlled GUS activity was high in the vasculature
      of leaves, roots, stems and flowers, as well as styles and siliques. A null T-DNA
      knockout mutant of AtAGP19 was obtained and compared to wild-type (WT) plants.
      The atagp19 mutant had: (i) smaller, rounder and flatter rosette leaves, (ii)
      lighter-green leaves containing less chlorophyll, (iii) delayed growth, (iv)
      shorter hypocotyls and inflorescence stems, and (v) fewer siliques and less seed
      production. Several abnormalities in cell size, number, shape and packing were
      also observed in the mutant. Complementation of this pleiotropic mutant with the
      WT AtAGP19 gene restored the WT phenotypes and confirmed that AtAGP19 functions
      in various aspects of plant growth and development, including cell division and
      expansion, leaf development and reproduction.

PMID- 17217457
TI  - The hyper-fluorescent trichome phenotype of the brt1 mutant of Arabidopsis is the
      result of a defect in a sinapic acid: UDPG glucosyltransferase.
AB  - Sinapoylmalate is a major phenylpropanoid that is accumulated in Arabidopsis. Its
      presence causes the adaxial surface of leaves to fluoresce blue under UV light,
      and mutations that lead to lower levels of sinapoylmalate decrease UV-induced
      leaf fluorescence. The Arabidopsis bright trichomes 1 (brt1) mutant was first
      identified in a screen for mutants that exhibit a reduced epidermal fluorescence
      phenotype; however, subsequent examination of the mutant revealed that its
      trichomes are hyper-fluorescent. The results from genetic mapping and
      complementation analyses showed that BRT1 (At3g21560) encodes UGT84A2, a
      glucosyltransferase previously shown to be capable of using sinapic acid as a
      substrate. Residual levels of sinapoylmalate and sinapic acid:UDP-glucose
      glucosyltransferase activity in brt1 leaves suggest that BRT1 is one member of a
      family of partially redundant glycosyltransferases that function in Arabidopsis
      sinapate ester biosynthesis. RT-PCR analysis showed that BRT1 is expressed
      through all stages of plant life cycle, a result consistent with the impact of
      the brt1 mutation on both leaf sinapoylmalate levels and seed sinapoylcholine
      content. Finally, the compound accumulated in brt1 trichomes was identified as a
      sinapic acid-derived polyketide, indicating that when sinapic acid glycosylation
      is reduced, a portion of it is instead activated to its CoA thioester, which then
      serves as a substrate for chalcone synthase.

PMID- 17217458
TI  - The miRNA156/157 recognition element in the 3' UTR of the Arabidopsis SBP box
      gene SPL3 prevents early flowering by translational inhibition in seedlings.
AB  - miRNAs are a class of versatile small RNAs that control gene expression post
      transcriptionally, governing many facets of plant cell functions. They interact
      with their target mRNA at a site of sequence complementarity and modulate their
      expression levels. Here, we provide evidence, based on transient assays and
      stable transgenic lines, that the 3' UTR of the Arabidopsis SBP box gene SPL3
      contains a functional miRNA-responsive element (MRE) that is complementary to
      miR156 and miRNA157. Seedlings of transgenic lines constitutively over-expressing
      an SPL3 transgene either carrying an unaltered or a disrupted MRE accumulate
      considerable levels of SPL3 transcripts. However, while the unaltered MRE UTR
      does not allow the expression of detectable levels of SPL3 protein, the altered
      MRE does. Translational inhibition thus provides an important mechanism for miRNA
      mediated post-transcriptional repression of SPL3. As a consequence of precocious
      translation of the constitutively expressed SPL3 transgene, due to the absence of
      a functional MRE, plants exhibit very early flowering in addition to frequent
      morphological changes.

PMID- 17217459
TI  - Dissecting the biosynthetic pathway for the bypass1 root-derived signal.
AB  - The Arabidopsis BYPASS1 (BPS1) gene is required for normal root and shoot
      development. In bps1 mutants, grafting and root excision experiments have shown
      that mutant roots produce a transmissible signal that is capable of arresting
      shoot development. In addition, we previously showed that growth of bps1 mutants
      on the carotenoid biosynthesis inhibitor fluridone resulted in partial rescue of
      both leaf and root defects. These observations suggest that a single mobile
      carotenoid-derived signal affects both root and shoot development. Here, we
      describe further characterization of the bps1 root-derived signal using genetic
      and biosynthetic inhibitor approaches. We characterized leaf and root development
      in double mutants that combined the bps1 mutant with mutants that have known
      defects in genes encoding carotenoid processing enzymes or defects in responses
      to carotenoid-derived abscisic acid. Our studies indicate that the mobile signal
      is neither abscisic acid nor the MAX-dependent hormone that regulates shoot
      branching, and that production of the signal does not require the activity of any
      single carotenoid cleavage dioxygenase. In addition, our studies with CPTA, a
      lycopene cyclase inhibitor, show that signal production requires synthesis of
      beta-carotene and its derivatives. Furthermore, we show a direct requirement for
      carotenoids as signal precursors, as the GUN plastid-to-nucleus signaling pathway
      is not required for phenotypic rescue. Together, our results suggest that bps1
      roots produce a novel mobile carotenoid-derived signaling compound.

PMID- 17217460
TI  - Early events in the pathogenicity of Pseudomonas syringae on Nicotiana
      benthamiana.
AB  - Conserved microbial molecules known as PAMPs (pathogen-associated molecular
      patterns) elicit defence responses in plants through extracellular receptor
      proteins. One important PAMP is the flagellin protein derived from motile
      bacteria. We show here that the solanaceous species Nicotiana benthamiana
      perceives the flagellin proteins of both pathogenic and non-host species of
      Pseudomonas syringae. The response to flagellin required a gene closely related
      to that encoding the Arabidopsis thaliana flagellin receptor that we designated
      NbFls2. In addition, silencing of NbFls2 led to increased growth of compatible,
      non-host and non-pathogenic strains of P. syringae. Thus, flagellin perception
      restricts growth of P. syringae strains on N. benthamiana. Pathogenic bacteria
      secrete effector proteins into the plant cell to enhance virulence. We tested the
      ability of several unrelated effectors to suppress PAMP-mediated defences. The
      effector proteins AvrPto and AvrPtoB, but not AvrRps4, suppressed all responses
      tested including the hypersensitive response induced by non-host flagellins and
      the oomycete elicitor INF1. Strikingly, transient expression of avrPto or avrPtoB
      stimulated the growth of non-pathogenic Agrobacterium tumefaciensin planta,
      suggesting that multiplication of this species is also restricted by PAMP
      perception. Unexpectedly, AvrPtoB but not AvrPto required the defence-associated
      genes Rar1, Sgt1 and Eds1 for suppression. This observation separates the
      respective mechanisms of the two effectors, and suggests that AvrPtoB may target
      the defence machinery directly for its suppressive effect.

PMID- 17217461
TI  - ABA induction of miR159 controls transcript levels of two MYB factors during
      Arabidopsis seed germination.
AB  - Upon seed imbibition, abscisic acid (ABA) levels decrease to allow embryos to
      germinate and develop into seedlings. However, under abiotic stress conditions,
      ABA levels remain high, and growth and development are arrested. Several
      transcription factors, including abscisic acid-insensitive (ABI)3 and ABI5, are
      known to control this developmental checkpoint. Here, we show that, in
      germinating Arabidopsis thaliana seeds, ABA induces the accumulation of microRNA
      159 (miR159) in an ABI3-dependent fashion, and miRNA159 mediates cleavage of
      MYB101 and MYB33 transcripts in vitro and in vivo. The two MYB transcription
      factors function as positive regulators of ABA responses, as null mutants of
      myb33 and myb101 show hyposensitivity to the hormone. Consistent with this,
      miR159 over-expression suppresses MYB33 and MYB101 transcript levels and renders
      plants hyposensitive to ABA, whereas transgenic plants over-expressing cleavage
      resistant forms of MYB33 and MYB101 are hypersensitive, as are plants over
      expressing the Turnip mosaic virus (TuMV) P1/HC-Pro viral protein that is known
      to inhibit miRNA function. Our results suggest that ABA-induced accumulation of
      miR159 is a homeostatic mechanism to direct MYB33 and MYB101 transcript
      degradation to desensitize hormone signaling during seedling stress responses.

PMID- 17217462
TI  - Temporal responses of transcripts, enzyme activities and metabolites after adding
      sucrose to carbon-deprived Arabidopsis seedlings.
AB  - Arabidopsis seedlings were subjected to 2 days of carbon starvation, and then
      resupplied with 15 mm sucrose. The transcriptional and metabolic response was
      analyzed using ATH1 arrays, real-time quantitative (q)RT-PCR analysis of >2000
      transcription regulators, robotized assays of enzymes from central metabolism and
      metabolite profiling. Sucrose led within 30 min to greater than threefold changes
      of the transcript levels for >100 genes, including 20 transcription regulators,
      15 ubiquitin-targeting proteins, four trehalose phosphate synthases, autophagy
      protein 8e, several glutaredoxins and many genes of unknown function. Most of
      these genes respond to changes of endogenous sugars in Arabidopsis rosettes,
      making them excellent candidates for upstream components of sugar signaling
      pathways. Some respond during diurnal cycles, consistent with them acting in
      signaling pathways that balance the supply and utilization of carbon in normal
      growth conditions. By 3 h, transcript levels change for >1700 genes. This
      includes a coordinated induction of genes involved in carbohydrate synthesis,
      glycolysis, respiration, amino acid and nucleotide synthesis, DNA, RNA and
      protein synthesis and protein folding, and repression of genes involved in amino
      acid and lipid catabolism, photosynthesis and chloroplast protein synthesis and
      folding. The changes of transcripts are followed by a delayed activation of
      central metabolic pathways and growth processes, which use intermediates from
      these pathways. Sucrose and reducing sugars accumulate during the first 3-8 h,
      and starch for 24 h, showing that there is a delay until carbon utilization for
      growth recommences. Gradual changes of enzyme activities and metabolites are
      found for many metabolic pathways, including glycolysis, nitrate assimilation,
      the shikimate pathway and myoinositol, proline and fatty acid metabolism. After 3
      8 h, there is a decrease of amino acids, followed by a gradual increase of
      protein.

PMID- 17217463
TI  - The ubiquitin pathway is required for innate immunity in Arabidopsis.
AB  - Plant defences require a multitude of tightly regulated resistance responses. In
      Arabidopsis, the unique gain-of-function mutant suppressor of npr1-1 constitutive
      1 (snc1) carries a point mutation in a Resistance (R)-gene, resulting in
      constitutive activation of defence responses without interaction with pathogens.
      This has allowed us to identify various downstream signalling components
      essential in multiple defence pathways. One mutant that suppresses snc1-mediated
      constitutive resistance is modifier of snc1 5 (mos5), which carries a 15-bp
      deletion in UBA1, one of two ubiquitin-activating enzyme genes in Arabidopsis. A
      mutation in UBA2 does not suppress snc1, suggesting that these two genes are not
      equally required in Arabidopsis disease resistance. On the other hand, a mos5
      uba2 double mutant is lethal, implying partial redundancy of the two homologues.
      Apart from affecting snc1-mediated resistance, mos5 also exhibits enhanced
      disease susceptibility to a virulent pathogen and is impaired in response to
      infection with avirulent bacteria carrying the protease elicitor AvrRpt2. The
      mos5 mutation in the C-terminus of UBA1 might affect binding affinity of the
      downstream ubiquitin-conjugating enzymes, thus perturbing ubiquitination of
      target proteins. Furthermore, SGT1b and RAR1, which are necessary for resistance
      conferred by the SNC1-related R-genes RPP4 and RPP5, are dispensable in snc1
      mediated resistance. Our data reveal the definite requirement for the
      ubiquitination pathway in the activation and downstream signalling of several R
      proteins.

PMID- 17217464
TI  - Dynamics of MONOPTEROS and PIN-FORMED1 expression during leaf vein pattern
      formation in Arabidopsis thaliana.
AB  - Genetic evidence links the Arabidopsis MONOPTEROS (MP) and PIN-FORMED1 (PIN1)
      genes to the patterning of leaf veins. To elucidate their potential functions and
      interactions in this process, we have assessed the dynamics of MP and PIN1
      expression during vascular patterning in Arabidopsis leaf primordia. Both genes
      undergo a dynamic process of gradual refinement of expression into files one to
      two cells wide before overt vascular differentiation. The subcellular
      distribution of PIN1 is also gradually refined from a non-polar distribution in
      isodiametric cells to strongly polarized in elongated procambial cells and
      provides an indication of overall directions of auxin flow. We found evidence
      that MP expression can be activated by auxin exposure and that PIN1 as well as
      DR5::GUS expression is defective in mp mutant leaves. Taken together the results
      suggest a feedback regulatory loop that involves auxin, MP and PIN1 and provide
      novel experimental support for the canalization-of-auxin-flow hypothesis.

PMID- 17217465
TI  - The Arabidopsis PsbO2 protein regulates dephosphorylation and turnover of the
      photosystem II reaction centre D1 protein.
AB  - The extrinsic photosystem II (PSII) protein of 33 kDa (PsbO), which stabilizes
      the water-oxidizing complex, is represented in Arabidopsis thaliana (Arabidopsis)
      by two isoforms. Two T-DNA insertion mutant lines deficient in either the PsbO1
      or the PsbO2 protein were retarded in growth in comparison with the wild type,
      while differing from each other phenotypically. Both PsbO proteins were able to
      support the oxygen evolution activity of PSII, although PsbO2 was less efficient
      than PsbO1 under photoinhibitory conditions. Prolonged high light stress led to
      reduced growth and fitness of the mutant lacking PsbO2 as compared with the wild
      type and the mutant lacking PsbO1. During a short period of treatment of detached
      leaves or isolated thylakoids at high light levels, inactivation of PSII electron
      transport in the PsbO2-deficient mutant was slowed down, and the subsequent
      degradation of the D1 protein was totally inhibited. The steady-state levels of
      in vivo phosphorylation of the PSII reaction centre proteins D1 and D2 were
      specifically reduced in the mutant containing only PsbO2, in comparison with the
      mutant containing only PsbO1 or with wild-type plants. Phosphorylation of PSII
      proteins in vitro proceeded similarly in thylakoid membranes from both mutants
      and wild-type plants. However, dephosphorylation of the D1 protein occurred much
      faster in the thylakoids containing only PsbO2. We conclude that the function of
      PsbO1 in Arabidopsis is mostly in support of PSII activity, whereas the
      interaction of PsbO2 with PSII regulates the turnover of the D1 protein,
      increasing its accessibility to the phosphatases and proteases involved in its
      degradation.

PMID- 17217466
TI  - Microarray analysis reveals altered expression of a large number of nuclear genes
      in developing cytoplasmic male sterile Brassica napus flowers.
AB  - To gain new insights into the mechanism underlying cytoplasmic male sterility
      (CMS), we compared the nuclear gene expression profiles of flowers of a Brassica
      napus CMS line with that of the fertile B. napus maintainer line using
      Arabidopsis thaliana flower-specific cDNA microarrays. The CMS line used has a B.
      napus nuclear genome, but has a rearranged mitochondrial (mt) genome consisting
      of both B. napus and A. thaliana DNA. Gene expression profiling revealed that a
      large number of genes differed in expression between the two lines. For example,
      nuclear genes coding for proteins that are involved in protein import into
      organelles, genes expressed in stamens and pollen, as well as genes implicated in
      either cell-wall remodeling or architecture, were repressed in the CMS line
      compared with B. napus. These results show that the mt genome of the CMS line
      strongly influences nuclear gene expression, and thus reveal the importance of
      retrograde signalling between the mitochondria and the nucleus. Furthermore,
      flowers of the CMS line are characterized by a replacement of stamens with
      carpelloid organs, and thus partially resemble the APETALA3 (AP3) and PISTILLATA
      (PI) mutants. In accordance with this phenotype, AP3 expression was downregulated
      in the stamens, shortly before these organs developed carpelloid characteristics,
      even though it was initiated correctly. Repression of PI succeeded that of AP3
      and might be a consequence of a loss of AP3 activity. These results suggest that
      AP3 expression in stamens depends on proper mt function and a correct nuclear-mt
      interaction, and that mt alterations cause the male sterility phenotype of the
      CMS line.

PMID- 17217467
TI  - Single-stranded DNA binding factor AtWHY1 modulates telomere length homeostasis
      in Arabidopsis.
AB  - Telomere homeostasis, a process that is essential for the maintenance of
      chromosome integrity, is regulated by telomerase and a collection of associated
      proteins. By mass spectrometry we have identified a new telomeric protein encoded
      by the AtWHY1 (Arabidopsis thaliana Whirly 1) gene in Arabidopsis. AtWHY1
      specifically binds the single-stranded plant telomeric DNA sequences, but not
      double-stranded telomeric DNA. To gain insights into the function of AtWHY1 in
      telomere biogenesis, we have identified two Arabidopsis lines harboring T-DNA
      insertions in AtWHY1. These lines exhibit neither growth nor developmental
      defects. However, AtWHY1-deficient plants show a steady increase in the length of
      telomere tracts over generations. This telomere elongation is correlated with a
      significant increase in telomerase activity. On the contrary, transgenic plants
      expressing AtWHY1 show a decreased telomerase activity and shortened telomeres.
      The evidence presented here indicates that AtWHY1 is a new family of telomere end
      binding proteins that plays a role in regulating telomere-length homeostasis in
      Arabidopsis.

PMID- 17217468
TI  - HY5 is a point of convergence between cryptochrome and cytokinin signalling
      pathways in Arabidopsis thaliana.
AB  - Blue-light-dependent photomorphogenesis in Arabidopsis is regulated principally
      by the cryptochrome flavin-type photoreceptors, which control hypocotyl growth
      inhibition, cotyledon and leaf expansion, and the expression of light-regulated
      genes. Interestingly the plant hormone cytokinin induces similar responses when
      added exogenously to germinating seedlings, suggesting a link between
      cryptochrome and cytokinin signalling pathways. In this work we explore the
      relationship between cryptochrome and cytokinin signalling pathways in the
      promotion of photomorphogenesis. The effect of exogenously added cytokinins on
      hypocotyl growth inhibition occurs in the dark, and is largely independent and
      additive to that of cryptochromes in blue light, via distinct signalling
      pathways. By contrast, cytokinin-dependent stimulation of anthocyanin
      accumulation occurs only in light, and interacts with the signalling pathway
      downstream of cryptochrome 1 (CRY1) at the level of transcript accumulation of
      anthocyanin biosynthetic genes. Mutants in elongated hypocotyl 5 (hy5), a
      downstream intermediate in the CRY1 signalling pathway, show a reduced induction
      of anthocyanin accumulation in blue light by cytokinins, similar to that observed
      for cryptochrome (cry1) mutants. Furthermore cytokinins are shown to increase
      levels of HY5 protein accumulation, suggesting that cytokinins may function by
      reducing HY5 degradation by COP1 (constitutively photomorphogenic 1). As both
      cryptochrome and cytokinin signalling pathways increase HY5 protein levels, and
      as HY5 binds to the promoters of anthocyanin biosynthetic enzymes to stimulate
      gene expression, it is concluded that the regulation of HY5 protein stability
      represents a point of convergence between cryptochrome and cytokinin signalling
      pathways.

PMID- 17217469
TI  - The Arabidopsis thaliana sulfiredoxin is a plastidic cysteine-sulfinic acid
      reductase involved in the photooxidative stress response.
AB  - The 2-cysteine peroxiredoxins (2-Cys-Prxs) are antioxidants that reduce peroxides
      through a thiol-based mechanism. During catalysis, these ubiquitous enzymes are
      occasionally inactivated by the substrate-dependent oxidation of the catalytic
      cysteine to the sulfinic acid (-SO2H) form, and are reactivated by reduction by
      sulfiredoxin (Srx), an enzyme recently identified in yeast and in mammal cells.
      In plants, 2-Cys-Prxs constitute the most abundant Prxs and are located in
      chloroplasts. Here we have characterized the unique Srx gene in Arabidopsis
      thaliana (AtSrx) from a functional point of view, and analyzed the phenotype of
      two AtSrx knockout (AtSrx-) mutant lines. AtSrx is a chloroplastic enzyme
      displaying sulfinic acid reductase activity, as shown by the ability of the
      recombinant AtSrx to reduce the overoxidized 2-Cys-Prx form in vitro, and by the
      accumulation of the overoxidized Prx in mutant lines lacking Srx in vivo.
      Furthermore, AtSrx mutants exhibit an increased tolerance to photooxidative
      stress generated by high light combined with low temperature. These data
      establish that, as in yeast and in mammals, plant 2-Cys-Prxs are subject to
      substrate-mediated inactivation reversed by Srx, and suggest that the 2-Cys-Prx
      redox status and sulfiredoxin are parts of a signaling mechanism participating in
      plant responses to oxidative stress.

PMID- 17217470
TI  - The phenotype of soluble starch synthase IV defective mutants of Arabidopsis
      thaliana suggests a novel function of elongation enzymes in the control of starch
      granule formation.
AB  - All plants and green algae synthesize starch through the action of the same five
      classes of elongation enzymes: the starch synthases. Arabidopsis mutants
      defective for the synthesis of the soluble starch synthase IV (SSIV) type of
      elongation enzyme have now been characterized. The mutant plants displayed a
      severe growth defect but nonetheless accumulated near to normal levels of
      polysaccharide storage. Detailed structural analysis has failed to yield any
      change in starch granule structure. However, the number of granules per plastid
      has dramatically decreased leading to a large increase in their size. These
      results, which distinguish the SSIV mutants from all other mutants reported to
      date, suggest a specific function of this enzyme class in the control of granule
      numbers. We speculate therefore that SSIV could be selectively involved in the
      priming of starch granule formation.

PMID- 17217471
TI  - Molecular and functional analysis of phosphomannomutase (PMM) from higher plants
      and genetic evidence for the involvement of PMM in ascorbic acid biosynthesis in
      Arabidopsis and Nicotiana benthamiana.
AB  - Phosphomannomutase (PMM) catalyzes the interconversion of mannose-6-phosphate and
      mannose-1-phosphate. However, systematic molecular and functional investigations
      on PMM from higher plants have hitherto not been reported. In this work, PMM
      cDNAs were isolated from Arabidopsis, Nicotiana benthamiana, soybean, tomato,
      rice and wheat. Amino acid sequence comparisons indicated that plant PMM proteins
      exhibited significant identity to their fungal and mammalian orthologs. In line
      with the similarity in primary structure, plant PMM complemented the sec53-6
      temperature sensitive mutant of Saccharomyces cerevisiae. Histidine-tagged
      Arabidopsis PMM (AtPMM) purified from Escherichia coli converted mannose-1
      phosphate into mannose-6-phosphate and glucose-1-phosphate into glucose-6
      phosphate, with the former reaction being more efficient than the latter one. In
      Arabidopsis and N. benthamiana, PMM was constitutively expressed in both
      vegetative and reproductive organs. Reducing the PMM expression level through
      virus-induced gene silencing caused a substantial decrease in ascorbic acid (AsA)
      content in N. benthamiana leaves. Conversely, raising the PMM expression level in
      N. benthamiana using viral-vector-mediated ectopic expression led to a 20-50%
      increase in AsA content. Consistent with this finding, transgenic expression of
      an AtPMM-GFP fusion protein in Arabidopsis also increased AsA content by 25-33%.
      Collectively, this study improves our understanding on the molecular and
      functional properties of plant PMM and provides genetic evidence on the
      involvement of PMM in the biosynthesis of AsA in Arabidopsis and N. benthamiana
      plants.

PMID- 17217472
TI  - Metabolite profiling of plant carotenoids using the matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry.
AB  - Although modern MS has facilitated the advent of metabolomics, some natural
      products such as carotenoids are not readily compatible to detection by MS. In
      the present article, we describe how matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry (MALDI/TOF-MS) can be utilized to acquire mass
      spectra of carotenoids effectively. The procedure is sensitive (pmole range),
      reduces 'spot to spot' variation and provides high mass accuracy, thus aiding
      identification. The technique has been applied in vivo to the analysis of
      carotenoids in isolated plant cells and in vitro to three applications: (i) to
      show compatibility with purification methods such as LC, TLC and HPLC; (ii) for
      the rapid identification and quantification (by isotope dilution) of carotenoids
      present in crude extracts from plant tissues and whole cells; (iii) simultaneous
      semi-quantitative determination of carotenoids metabolites (m/z values) in crude
      plant extracts. Multivariate analysis of the recorded m/z values shows the
      effectiveness of the procedure in distinguishing genotypes from each other. In
      addition, the utility of the technique has been demonstrated on two mutant tomato
      populations, to determine alterations in carotenoid content, and a comparison
      made with traditional HPLC-photodiode array analysis. These data show that
      MALDI/TOF-MS can be used to rapidly profile, identify and quantify plant
      carotenoids reproducibly, as well as detecting other metabolites (m/z) in complex
      biological systems.

PMID- 17217473
TI  - Rapid assessment of severe cognitive impairment in individuals with developmental
      disabilities.
AB  - BACKGROUND: Most standardized intelligence tests require more than 1 hour for
      administration, which is problematic when evaluating individuals with
      intellectual disabilities and developmental disabilities (IDDD), because a
      significant proportion of these individuals can not tolerate lengthy evaluations.
      Furthermore, most standardized intelligence tests are of limited usefulness for
      individuals with severe cognitive deficits because of floor effects. METHODS: A
      number of low-difficulty items were selected from standardized tests. A total of
      271 participants with profound, severe, moderate and mild levels of cognitive
      impairment took part in this study. In the formative phase, 68 participants were
      evaluated with the selected items, and those items that differentiated between
      levels of cognitive impairment were retained in the battery. The instrument was
      then modified and standardized with an additional 203 participants. RESULTS: The
      instrument, referred to as the Rapid Assessment for Developmental Disabilities
      (RADD), required 10-25 min for administration. Internal reliability estimates
      from the RADD total score and from individual subtests satisfied conventional and
      rigorous statistical criteria (median alpha r = 0.93). The RADD total score was
      strongly correlated with the level of cognitive impairment (rho = 0.86). The RADD
      total score and individual subtests differentiated between all levels of
      cognitive impairment ( Wilks Lambda = 0.135, F(42,525.832) = 12.075, P < 0.001).
      Receiver operating characteristic curves indicated the instrument was
      particularly sensitive to the cognitive abilities of the most seriously impaired
      participants. CONCLUSIONS: The RADD, composed of low-difficulty items from
      published tests, is rapidly administered, assesses a wide range of cognitive
      skills and differentiates among all levels of cognitive impairment. The battery
      has clinical utility with populations exhibiting short attention spans because of
      its ability to quickly assess a wide range of cognitive abilities. The RADD also
      has research potential for the documentation of cognitive function in studies of
      individuals with IDDD.

PMID- 17217474
TI  - Longitudinal analysis of inpatient care utilization among people with
      intellectual disabilities: 1999-2002.
AB  - BACKGROUND: There has been no longitudinal study in Taiwan to identify the nature
      and the scale of medical care utilization of people with intellectual
      disabilities (IDs) up to the present. The aim of this study is to describe
      inpatient utilization among people under ID care in institutions in order to
      identify the pattern of medical care needs and the factors affecting utilization
      in Taiwan. METHOD: The subject cohort was 168 individuals with ID who were cared
      for by a large public disability institution from 1999 to 2002 in Taipei, Taiwan.
      RESULTS: On the examination of the inpatient care that these persons underwent,
      it was found that these individuals had a heightened need (inpatient rate: 10.1
      14.9%) for inpatient care compared with the general population with disabilities
      (9.37%) in Taiwan. The main reasons for hospitalization were pneumonia,
      gastrointestinal disorders, cellulites, orthopaedic problems, epilepsy and
      bronchitis. Using the full model of Generalized Estimating Equations for
      inpatient care utilization, the factors including low income family, living in an
      institution, being a subject with cerebral palsy and being a high outpatient user
      all influenced the use of inpatient care. CONCLUSIONS: This study highlights that
      health authorities need to promote health planning more in order to ensure an
      excellent quality of health monitoring and health promotion among people with ID
      cared for by institutions.

PMID- 17217475
TI  - Predictors of care-giver stress in families of preschool-aged children with
      developmental disabilities.
AB  - BACKGROUND: This study examined the predictors, mediators and moderators of
      parent stress in families of preschool-aged children with developmental
      disability. METHOD: One hundred and five mothers of preschool-aged children with
      developmental disability completed assessment measures addressing the key
      variables. RESULTS: Analyses demonstrated that the difficulty parents experienced
      in completing specific care- giving tasks, behaviour problems during these care
      giving tasks, and level of child disability, respectively, were significant
      predictors of level of parent stress. In addition, parents' cognitive appraisal
      of care-giving responsibilities had a mediating effect on the relationship
      between the child's level of disability and parent stress. Mothers' level of
      social support had a moderating effect on the relationship between key
      independent variables and level of parent stress. CONCLUSIONS: Difficulty of care
      giving tasks, difficult child behaviour during care-giving tasks, and level of
      child disability are the primary factors which contribute to parent stress.
      Implications of these findings for future research and clinical practice are
      outlined.

PMID- 17217476
TI  - Pain's impact on adaptive functioning.
AB  - BACKGROUND: Pain interferes with the functioning of typical children, but no
      study has examined its effect on children with pre-existing intellectual
      disabilities (ID). METHODS: Caregivers of 63 children observed their children for
      2-h periods and recorded in 1-week diaries: pain presence, cause, intensity and
      duration. Caregivers also recorded the children's performance of pre-existing
      skills during each period. Proportion of skills displayed when pain was present
      and absent was compared. Fifty caregivers completed a second set of observations
      when pain was present and absent. RESULTS: Comparison of the first set of
      observations indicated children displayed significantly more abilities (64%) when
      pain-free (Pain-Free Day 1), than when pain was present (54%; Pain Day 1).
      Children displayed 64% of their possible abilities during Pain-Free Day 2, but
      only 53% during Pain Day 2. Pain impacted all areas of function (communication,
      daily living, social and motor skills). Children's physical and demographic
      characteristics did not moderate the impact of pain on function, but functioning
      of children with more severe ID was most impacted by pain. CONCLUSIONS: Children
      perform fewer adaptive skills when pain is present. This could affect long-term
      functioning as well, through reduced practice of skills.

PMID- 17217477
TI  - Trends in residential policies and services for people with intellectual
      disabilities in Taiwan.
AB  - BACKGROUND: In Taiwan, 92-95% of people with an intellectual disability (ID) live
      with their families, with the remaining residing in residential facilities.
      Instead of funding community-living alternatives, the Taiwanese Government funds
      only registered facilities as part of its residential policies and services. The
      purpose of this study was to evaluate current policies and services trends
      regarding people with an ID in Taiwan. METHODS: Both documentary research, such
      as an analysis of policies, services programmes, official statistics, surveys,
      reports and funding provision reports, and a mail survey, were conducted to
      examine current trends and characteristics of the 96 residential settings
      available for people with an ID in Taiwan. RESULTS: During the 1990s in Taiwan,
      residential programmes for people with an ID showed the biggest growth since
      1952. Since the first 'Community Home' was launched in 1990, the number of
      smaller scale residential settings with a unit size of less than 30 has grown
      significantly, particularly since 2000. However, the rate of institutionalization
      of people with an ID and who live in the institutions has also risen.
      CONCLUSIONS: In Taiwan, unlike in Western societies, residential services for
      people with an ID provided by formal care systems are tending to grow in number,
      and these include both large and smaller residential settings.

PMID- 17217478
TI  - Supported employment improves cognitive performance in adults with Autism.
AB  - BACKGROUND: The purpose of this study was to examine the effects of a supported
      employment programme on measures of executive functions for 44 adults with
      autism, assessed at the beginning and the end of the programme period. The
      average length of time of the community employment was 30 months. METHODS: Based
      on their predominant work activity over the study period, participants were
      classified into two groups: supported employment and unemployed. At the start of
      the programme, the groups did not differ on any of the cognitive measures.
      RESULTS: Repeated measures analysis of variance (anova) demonstrated that by the
      end of the programme, the supported employment group showed higher scores for
      executive functions on variables of CANTAB (Spatial Span Task--span length
      recalled; Spatial Working Memory Task--strategy; Planning task 'Stockings of
      Cambridge'--problems solved in minimum moves; Planning task 'Stockings of
      Cambridge'--mean planning time) and other tasks such as Trail Making Test - part
      B, time; Matching Familiar Figures (first answer and errors). In contrast, the
      unemployed group showed no change over time in their cognitive performance.
      CONCLUSION: Results of this study suggested that vocational rehabilitation
      programmes have a beneficial impact upon cognitive performance in people with
      autism.

PMID- 17217479
TI  - A multidisciplinary approach to the management of individuals with fragile X
      syndrome.
AB  - BACKGROUND: Fragile X syndrome (FXS) is the most common inherited form of
      intellectual disability. Since the identification of the responsible gene (FMR1)
      and its protein (FMRP), there has been enormous progress in both clinical and
      pathogenetic research on the neurobehavioural aspects of the condition. However,
      studies regarding other medical problems anticipated in individuals with FXS are
      limited. A multidisciplinary study evaluating various causes of morbidity in the
      same group has not been published yet. METHODS: Twenty-four boys with FXS full
      mutation were recruited out of a larger group of 103 diagnosed in one centre over
      the past 10 years. Ear nose and throat, eye and cardiac examinations were
      performed in addition to routine cognitive, behavioural, neurological and speech
      and language assessments. RESULTS: The average IQ score was 49.8 +/- 20 (range 25
      90). There were four patients (18%) with IQ above 70. Using DSM-IV, attention
      deficit hyperactivity disorder was diagnosed in five boys out of 22 examined
      (23%), while 32% were diagnosed with pervasive developmental disorder. The
      seizure frequency was 17%. A psychiatric disorder was diagnosed in six out of
      eight boys with electroencephalogram abnormalities (75%). Minimal conductive
      hearing loss was found in five (5/22) patients. There was significant delay in
      both expressive and receptive language skills. Ocular findings were refractive
      errors (13%) and strabismus (4.4%). Mitral valve prolapsus (MVP) was observed in
      3/22 (13.7%) patients and aortic annulus dilatation was present in 2/22 (9%)
      patients. CONCLUSIONS: Frequency of psychiatric diagnoses made with DSM-IV were
      in parallel to those reported in the literature. Comorbidity of seizures and
      psychiatric disorders was noteworthy. The percentage of 'high-functioning' full
      mutation males supports the previous observations. Ear nose and throat and eye
      examination revealed remarkably lower prevalence of abnormal findings than
      reported. MVP was slightly less frequent compared with the single study in the
      literature. Age at the time of examination had an effect on the outcome of
      cardiac evaluation. These findings will guide us in future management of the
      group of patients followed in our institution. The protocol applied provides an
      applicable outline for multidisciplinary institutional settings dealing with
      individuals with FXS.

PMID- 17217480
TI  - Verbal working memory in children with mild intellectual disabilities.
AB  - BACKGROUND: Previous research into working memory of individuals with
      intellectual disabilities (ID) has established clear deficits. The current study
      examined working memory in children with mild ID (IQ 55-85) within the framework
      of the Baddeley model, fractionating working memory into a central executive and
      two slave systems, the phonological loop and visuo-spatial sketchpad. METHOD:
      Working memory was investigated in three groups: 50 children with mild ID (mean
      age 15 years 3 months), 25 chronological age-matched control children (mean age
      15 years 3 months) and 25 mental age-matched control children (mean age 10 years
      10 months). The groups were given multiple assessments of the phonological-loop
      and central-executive components. RESULTS: The results showed that the children
      with mild ID had an intact automatic rehearsal, but performed poorly on
      phonological-loop capacity and central-executive tests when compared with
      children matched for chronological age, while there were only minimal differences
      relative to the performance of the children matched for mental age. CONCLUSIONS:
      This overall pattern of results is consistent with a developmental delay account
      of mild ID. The finding of a phonological-loop capacity deficit has important
      implications for the remedial training of children with mild ID.

PMID- 17217483
TI  - Recommendations for the surveillance of young women at increased risk for breast
      cancer.
AB  - A review of the published reports regarding screening for breast cancer in young,
      at-risk women has been undertaken. Draft recommendations for surveillance of
      these women with imaging methods such as mammography, ultrasound and MRI have
      been made.

PMID- 17217484
TI  - Role of radiotherapy in the management of organ transplant recipients diagnosed
      with non-melanoma skin cancers.
AB  - Organ transplantation has had a major effect on the lives of thousands of
      patients worldwide. In Australia and New Zealand, over 13 000 patients have
      become organ transplant recipients (OTR). Following transplantation, patients
      require lifelong immunosuppression to prevent organ rejection. The loss of immune
      surveillance results in OTR experiencing a higher incidence of infection and
      malignancy in comparison with the general (immunocompetent) population. Non
      melanoma skin cancer (NMSC) is the most common malignancy worldwide, arising most
      often on the sun-exposed head and neck. Organ transplant recipients experience a
      higher incidence of NMSC when compared with the general population and a higher
      incidence of squamous cell carcinoma compared with basal cell carcinoma. Organ
      transplant recipients also develop NMSC at a younger age and experience multiple
      new NMSC. Australians experience the highest incidence of NMSC in the world with
      a consequence that NMSC arising in OTR can lead to significant morbidity and even
      mortality. Radiation oncologists treating patients with skin cancer will almost
      certainly make recommendations in the setting of NMSC arising in OTR. The aim of
      this article is to discuss the role of radiotherapy in the management of OTR
      diagnosed with NMSC. The emphasis will be on the treatment of patients with a
      high-risk NMSC (e.g. squamous cell carcinoma, Merkel cell carcinoma, unfavourable
      basal cell carcinoma) because this reflects the most common clinical scenario in
      which a recommendation of radiotherapy, usually adjuvant, may be considered.

PMID- 17217485
TI  - Radiation: facts, fallacies and phobias.
AB  - There is frequent debate in the media and the scientific published reports about
      the use of radiation for diagnosis and treatment, the benefits and risks of the
      nuclear industry, uranium mining and the storage of radioactive wastes. Driving
      this debate is increasing concern about reliance on fossil fuels for power
      generation for which alternatives are required. Unfortunately, there is generally
      a poor understanding of the relevant basic sciences compounded by widespread
      irrational fear of irradiation (radiation phobia). Radioactivity, with special
      reference to uranium and plutonium is simply described. How radiation affect
      tissues and the potential hazards to individuals and populations are explained.
      The origins of radiation phobia and its harmful consequences are examined.
      Whether we like it or not, Australia is heavily involved in the uranium industry
      by virtue of having one-third of the world's known reserves, exports of which are
      worth approximately $470m annually. As this paper has been written as simply as
      possible, it may also be of interest to readers who may have had little
      scientific training. It may be downloaded from the web using references provided
      in this article. It is concluded that ignorance and fear are major impediments to
      rational debate on radiation issues.

PMID- 17217486
TI  - Imaging and intervention of retroperitoneal fibrosis.
AB  - Retroperitoneal fibrosis is a rare condition characterized by the development of
      fibrous plaques in the retroperitoneal space. The fibrous plaques
      characteristically arise distal to the bifurcation of the abdominal aorta and
      progress to encase the iliac vessels distally and are defined by the associated
      encasement of one or both ureters. Imaging plays an important role in not only
      establishing the diagnosis, but also in monitoring disease progression.
      Historically, the radiological diagnosis was made predominantly by intravenous
      urography and retrograde pyelography. More recently, advances in cross-sectional
      imaging with ultrasound and contrast-enhanced CT have allowed for a more precise
      diagnosis as well as helping to accurately define the extent of the disease. At
      our institution, we have found ultra-fast MRI to also play a useful role in
      establishing the diagnosis. In particular, magnetic resonance urography using
      HASTE (half Fourier-acquired single shot turbo spin-echo) sequences allow a safe
      alternative to intravenous urography, particularly in patients with poor renal
      function. The purpose of this article is to describe the role of the various
      imaging methods available to the radiologist and to emphasize the important role
      that the interventional radiologist now plays, not only in obtaining tissue for
      diagnosis, but also in providing treatment of the disease by percutaneous
      nephrostomy drainage and subsequent stent placement in select cases.

PMID- 17217487
TI  - Central venous catheter placement by an interventional radiology unit: an
      Australian experience.
AB  - The aim of this retrospective study was to analyse the outcomes of central venous
      catheter (CVC) placement carried out by an interventional radiology unit. A
      review of our hospital records identified 331 consecutive patients who underwent
      insertion of a tunnelled or non-tunnelled CVC between January 2000 and December
      2004. Key outcome measures included the technical success rate of CVC insertion
      and the percentage of immediate (<24 h), early (24 h-30 days) and late (>30 days)
      complications. A total of 462 CVCs were placed under radiological guidance, with
      an overall success rate of 98.9%. Immediate complications included one
      pneumothorax, which was diagnosed 7 days after subclavian CVC insertion, and
      eight episodes of significant haematoma or bleeding within 24 h of CVC insertion.
      No cases were complicated by arterial puncture or air embolus. Catheter-related
      sepsis occurred in 2% of non-tunnelled CVC and 8.9% of tunnelled CVC. The overall
      incidence of catheter-related sepsis was 0.17 per 100 catheter days. As the
      demand for chemotherapy and haemodialysis grows with our ageing population,
      interventional radiology suites are well placed to provide a safe and reliable
      service for the placement of central venous access devices.

PMID- 17217488
TI  - Radiology teaching: essentials of a quality teaching programme.
AB  - Medical student teaching is an important component of radiology education.
      Despite the practice of radiology undergoing significant changes during the last
      two or three decades, the importance of radiology has not translated fully into
      medical school curricula in Australia and New Zealand. This article reviews the
      essential components of a quality medical student teaching programme.

PMID- 17217489
TI  - Using ultrasonic fetal size measurements to estimate gestational age in Brisbane,
      Australia.
AB  - The purpose of this paper was to construct population-specific charts of
      gestational age (GA) from antenatal ultrasound biometry assessment using a large
      sample of normal Australian pregnancies when examination was carried out to a
      standard protocol by experienced operators. All consenting eligible women
      attending a large Brisbane clinic between January 1993 and April 2003 with GA
      between 15 and 41 weeks, determined before examination from the last menstrual
      period date and concordant with the biometric-derived gestation published within
      the Australian Society for Ultrasound in Medicine (ASUM) policies and statements,
      were recruited into the prospective study if fulfilling the inclusion criteria.
      Biparietal diameter, femur length, abdominal circumference and head circumference
      measurements were recorded using ASUM standard protocol for mid and third
      trimester obstetric morphology scans. Statistical analyses were carried out using
      polynomial regression models and thorough diagnostic checks were undertaken.
      Included within the study were separate scans for 20,555 pregnancies from 17,660
      women. Equations, means and 95% reference intervals for GA were derived for each
      sonographic measurement. These new population-specific regression equations
      complement those previously published in the same sample of Australian
      pregnancies. Once validated, we believe they should form the basis of a new
      Australian standard for ASUM.

PMID- 17217490
TI  - Feasibility study on the MammoSite in early-stage breast cancer: initial
      experience.
AB  - The aims of this study were to evaluate the feasibility, practicality, efficacy
      and safety of the delivery of accelerated partial breast irradiation using the
      MammoSite for the boost phase. Six patients aged 53-69 years with stage T1N0,
      T2N0, Grade I-II invasive ductal carcinoma received 9-10 Gy prescribed at 1 cm
      from the MammoSite balloon surface in two fractions of 4.5-5 Gy 6 h apart. The
      MammoSite was inserted 20-37 days postoperatively. External beam radiation
      therapy to the whole breast commenced 1-5 days after accelerated partial breast
      irradiation. The maximum skin dose ranged from 3 to 9 Gy. The skin-cavity
      distance ranged from 7 to 19 mm. Local discomfort resolved as the scar healed
      spontaneously within 3-5 days. No Grade III or higher acute toxicity or local
      infection was recorded. The ease of insertion and accuracy of dosimetry makes the
      MammoSite suitable for use in properly selected women with early-stage breast
      cancer in a trial setting.

PMID- 17217491
TI  - Current practice when treating lung cancer in Australasia.
AB  - A multidisciplinary meeting was held by the radiation oncology department of
      South Western Sydney Area Cancer Services in March 2003. This meeting was
      advertised in all radiation oncology departments in Australia and New Zealand. As
      a precursor to this meeting, a survey was undertaken on the use of radiotherapy
      for treating lung cancer. All departments in Australia and New Zealand were asked
      to participate. The survey considered planning techniques, delivery set-up and
      prescription doses for non-small-cell and small-cell lung cancer and palliative
      and radical treatments. A wide range in the techniques used was seen across
      departments, particularly when prescription doses and fractionation were
      considered.

PMID- 17217492
TI  - Positron emission tomography of stage IV mucosa-associated lymphoid tissue
      lymphoma confined to the four major salivary glands.
AB  - In a patient with stage IVA marginal zone lymphoma, (18)F-fluorodeoxyglucose
      positron emission tomography indicated that the disease was confined to the four
      major salivary glands. The positron emission tomography findings encouraged the
      use of radiotherapy with curative intent in this case. After 30 Gy of external
      beam radiotherapy to the parotid and submandibular glands, the patient entered a
      complete remission and remains free from progression more than 4 years later.

PMID- 17217493
TI  - Epithelioid sarcoma of the median nerve mimicking a peripheral nerve sheath
      tumour.
AB  - We describe a case of epithelioid sarcoma of the median nerve in a 57-year-old
      woman presenting with symptoms and signs of carpal tunnel syndrome for 2 years.
      The clinical examination was suggestive of a wrist ganglion compressing the
      median nerve. Magnetic resonance imaging (MRI) showed a 5 cm x 3 cm mass
      involving the median nerve in the carpal tunnel and appearances mimicked a benign
      peripheral nerve sheath tumour. This report illustrates a rare tumour presenting
      in a rare location and emphasizes the atypical clinical and MRI features that
      should alert the radiologist to the possibility of a rare sarcoma mimicking a
      benign peripheral nerve sheath tumour.

PMID- 17217494
TI  - Hyaline-vascular type Castleman's disease of the pararenal retroperitoneum:
      multidetector CT findings.
AB  - We describe the case of a 40-year-old woman who presented with a pararenal
      hyaline-vascular type Castleman's disease that had an arterial supply from the
      renal artery and a draining vein as showed by multidetector CT. Identification of
      the renal artery relationship to the feeding vessel of the mass is critical to
      prevent potential surgical complications.

PMID- 17217495
TI  - Intercostal artery aneurysms complicating thoracic aortic coarctation: diagnosis
      with magnetic resonance angiography.
AB  - The case report of a 46-year-old woman diagnosed with complete aortic coarctation
      and multiple intercostal artery aneurysms using 'ultrafast time-resolved'
      multiphase contrast-enhanced magnetic resonance angiography and conventional
      single-phase, high-resolution breath-hold contrast-enhanced magnetic resonance
      angiogram techniques is presented. A review of intercoastal artery aneurysms
      occurring in conjunction with aortic coarctation and the various contrast
      enhanced magnetic resonance angiography techniques currently available is
      provided.

PMID- 17217496
TI  - Robinow syndrome: report of two cases and review of the literature.
AB  - We report two patients with Robinow syndrome, review the published literature and
      stress the importance and limitations of radiographic examination in the
      diagnosis of this disorder, which shows extreme clinical and radiographic
      variability. The radiographic differential diagnosis of Robinow syndrome is
      discussed.

PMID- 17217497
TI  - Portal circulation aneurysms: two case reviews.
AB  - Venous aneurysms of the superior mesenteric vein and portal vein are an uncommon
      occurrence and often an incidental finding. They can also be associated with
      hepatocellular disease and portal hypertension. We present CT and ultrasound
      findings of these entities. The management of venous aneurysms is generally
      conservative with serial imaging.

PMID- 17217498
TI  - Inguinal endometriosis attaching to the round ligament.
AB  - We report a case of endometriosis in the right inguinal region, attached to the
      right round ligament in a 28-year-old woman. At the age of 20, laparoscopic left
      ovarian cystectomy and pelvic adhesiolysis for endometriosis was carried out. She
      noticed a right tender groin mass 7 months previously, and the tumour size
      fluctuated with the menstrual cycle. A poorly circumscribed elastic hard mass,
      measuring 3 cm in diameter, was palpated in her right inguinal region. Magnetic
      resonance imaging showed a 2.5 cm x 2.5 cm mass in the right inguinal canal and a
      5.4 cm x 6.8 cm mass was seen in the left ovary. The mass enlarged during
      menstruation. The groin mass was removed, in addition to carrying out
      laparoscopic ovarian cystectomy. At operation, the groin mass was found to be in
      continuity with the round ligament of extraperitoneal portion. Histological
      diagnosis of endometriosis was made in both ovarian and inguinal tumours. After
      surgery, the pain disappeared completely. Worth mentioning is that MRI clearly
      showed the change of tumour size depending on the menstrual cycle, which aided in
      arriving at the correct diagnosis of endometriosis in an unusual location.

PMID- 17217499
TI  - Radiotherapy in the management of recurrent synovial chondromatosis.
AB  - Synovial chondromatosis is a rare, benign condition characterized by the
      formation of multiple cartilaginous nodules that are generally intra-articular
      and can lead to chronic pain and limit the function of involved joints. We report
      on the novel use of radiotherapy that was used to treat a 42-year-old man with
      rapid recurrences of extensive synovial chondromatosis in the knee refractory to
      multiple operations. Based on follow-up MRI scans and clinical findings, the
      disease process was halted with no progression seen over 5 years.

PMID- 17217500
TI  - Stage I seminoma in a 15-year-old boy.
AB  - Seminomas are very rare tumours in children and adolescents. We describe a case
      of seminoma in a 15-year-old boy who was managed with orchidectomy but no
      adjuvant therapy. He remains relapse-free 8 years after surgery as determined by
      clinical, radiological and serological surveillance. This study emphasizes the
      uncertainty over the need for adjuvant treatment in the management of seminoma in
      the adolescent patient, in particular in prepubescent children.

PMID- 17217502
TI  - SEQOPTICS: a protein sequence clustering system.
AB  - BACKGROUND: Protein sequence clustering has been widely used as a part of the
      analysis of protein structure and function. In most cases single linkage or graph
      based clustering algorithms have been applied. OPTICS (Ordering Points To
      Identify the Clustering Structure) is an attractive approach due to its emphasis
      on visualization of results and support for interactive work, e.g., in choosing
      parameters. However, OPTICS has not been used, as far as we know, for protein
      sequence clustering. RESULTS: In this paper, a system of clustering proteins,
      SEQOPTICS (SEQuence clustering with OPTICS) is demonstrated. The system is
      implemented with Smith-Waterman as protein distance measurement and OPTICS at its
      core to perform protein sequence clustering. SEQOPTICS is tested with four data
      sets from different data sources. Visualization of the sequence clustering
      structure is demonstrated as well. CONCLUSION: The system was evaluated by
      comparison with other existing methods. Analysis of the results demonstrates that
      SEQOPTICS performs better based on some evaluation criteria including Jaccard
      coefficient, Precision, and Recall. It is a promising protein sequence clustering
      method with future possible improvement on parallel computing and other protein
      distance measurements.

PMID- 17217501
TI  - Development of computations in bioscience and bioinformatics and its application:
      review of the Symposium of Computations in Bioinformatics and Bioscience
      (SCBB06).
AB  - The first symposium of computations in bioinformatics and bioscience (SCBB06) was
      held in Hangzhou, China on June 21-22, 2006. Twenty-six peer-reviewed papers were
      selected for publication in this special issue of BMC Bioinformatics. These
      papers cover a broad range of topics including bioinformatics theories,
      algorithms, applications and tool development. The main technical topics contain
      gene expression analysis, sequence analysis, genome analysis, phylogenetic
      analysis, gene function prediction, molecular interaction and system biology,
      genetics and population study, immune strategy, protein structure prediction and
      proteomics.

PMID- 17217503
TI  - The relationship between protein sequences and their gene ontology functions.
AB  - BACKGROUND: One main research challenge in the post-genomic era is to understand
      the relationship between protein sequences and their biological functions. In
      recent years, several automated annotation systems have been developed for the
      functional assignment of uncharacterized proteins. The underlying assumption of
      these systems is that similar sequences imply similar biological functions.
      However, it has been noted that matching sequences do not always infer similar
      functions. RESULTS: In this paper, we present the correlation between protein
      sequences and protein functions for the yeast proteome in the context of gene
      ontology. A novel measure is introduced to define the overall similarity between
      two protein sequences. The effects of the level as well as the size of a gene
      ontology group on the degree of similarity were studied. The similarity
      distributions at different levels of gene ontology trees are presented. To
      evaluate the theoretical prediction power of similar sequences, we computed the
      posterior probability of correct predictions. CONCLUSION: The results indicate
      that protein pairs of similar biological functions tend to have higher sequence
      similarity, although the similarity distribution in each functional group is
      heterogeneous and varies from group to group. We conclude that sequence
      similarity can serve as a key measure in protein function prediction. However,
      the resulting annotations must be verified through other means. A method that
      combines a broader range of measures is more likely to provide more accurate
      prediction. Our study indicates that the posterior probability of a correct
      prediction could serve as one of the key measures.

PMID- 17217504
TI  - Towards a better solution to the shortest common supersequence problem: the
      deposition and reduction algorithm.
AB  - BACKGROUND: The problem of finding a Shortest Common Supersequence (SCS) of a set
      of sequences is an important problem with applications in many areas. It is a key
      problem in biological sequences analysis. The SCS problem is well-known to be NP
      complete. Many heuristic algorithms have been proposed. Some heuristics work well
      on a few long sequences (as in sequence comparison applications); others work
      well on many short sequences (as in oligo-array synthesis). Unfortunately, most
      do not work well on large SCS instances where there are many, long sequences.
      RESULTS: In this paper, we present a Deposition and Reduction (DR) algorithm for
      solving large SCS instances of biological sequences. There are two processes in
      our DR algorithm: deposition process, and reduction process. The deposition
      process is responsible for generating a small set of common supersequences; and
      the reduction process shortens these common supersequences by removing some
      characters while preserving the common supersequence property. Our evaluation on
      simulated data and real DNA and protein sequences show that our algorithm
      consistently produces the best results compared to many well-known heuristic
      algorithms, and especially on large instances. CONCLUSION: Our DR algorithm
      provides a partial answer to the open problem of designing efficient heuristic
      algorithm for SCS problem on many long sequences. Our algorithm has a bounded
      approximation ratio. The algorithm is efficient, both in running time and space
      complexity and our evaluation shows that it is practical even for SCS problems on
      many long sequences.

PMID- 17217505
TI  - Determination of the minimum number of microarray experiments for discovery of
      gene expression patterns.
AB  - BACKGROUND: One type of DNA microarray experiment is discovery of gene expression
      patterns for a cell line undergoing a biological process over a series of time
      points. Two important issues with such an experiment are the number of time
      points, and the interval between them. In the absence of biological knowledge
      regarding appropriate values, it is natural to question whether the behaviour of
      progressively generated data may by itself determine a threshold beyond which
      further microarray experiments do not contribute to pattern discovery.
      Additionally, such a threshold implies a minimum number of microarray
      experiments, which is important given the cost of these experiments. RESULTS: We
      have developed a method for determining the minimum number of microarray
      experiments (i.e. time points) for temporal gene expression, assuming that the
      span between time points is given and the hierarchical clustering technique is
      used for gene expression pattern discovery. The key idea is a similarity measure
      for two clusterings which is expressed as a function of the data for progressive
      time points. While the experiments are underway, this function is evaluated. When
      the function reaches its maximum, it indicates the set of experiments reach a
      saturated state. Therefore, further experiments do not contribute to the
      discrimination of patterns. CONCLUSION: The method has been verified with two
      previously published gene expression datasets. For both experiments, the number
      of time points determined with our method is less than in the published
      experiments. It is noted that the overall approach is applicable to other
      clustering techniques.

PMID- 17217506
TI  - Improved Chou-Fasman method for protein secondary structure prediction.
AB  - BACKGROUND: Protein secondary structure prediction is a fundamental and important
      component in the analytical study of protein structure and functions. The
      prediction technique has been developed for several decades. The Chou-Fasman
      algorithm, one of the earliest methods, has been successfully applied to the
      prediction. However, this method has its limitations due to low accuracy,
      unreliable parameters, and over prediction. Thanks to the recent development in
      protein folding type-specific structure propensities and wavelet transformation,
      the shortcomings in Chou-Fasman method are able to be overcome. RESULTS: We
      improved Chou-Fasman method in three aspects. (a) Replace the nucleation regions
      with extreme values of coefficients calculated by the continuous wavelet
      transform. (b) Substitute the original secondary structure conformational
      parameters with folding type-specific secondary structure propensities. (c)
      Modify Chou-Fasman rules. The CB396 data set was tested by using improved Chou
      Fasman method and three indices: Q3, Qpre, SOV were used to measure this method.
      We compared the indices with those obtained from the original Chou-Fasman method
      and other four popular methods. The results showed that our improved Chou-Fasman
      method performs better than the original one in all indices, about 10-18%
      improvement. It is also comparable to other currently popular methods considering
      all the indices. CONCLUSION: Our method has greatly improved Chou-Fasman method.
      It is able to predict protein secondary structure as good as current popular
      methods. By locating nucleation regions with refined wavelet transform technology
      and by calculating propensity factors with larger size data set, it is likely to
      get a better result.

PMID- 17217507
TI  - Parallelization of multicategory support vector machines (PMC-SVM) for
      classifying microarray data.
AB  - BACKGROUND: Multicategory Support Vector Machines (MC-SVM) are powerful
      classification systems with excellent performance in a variety of data
      classification problems. Since the process of generating models in traditional
      multicategory support vector machines for large datasets is very computationally
      intensive, there is a need to improve the performance using high performance
      computing techniques. RESULTS: In this paper, Parallel Multicategory Support
      Vector Machines (PMC-SVM) have been developed based on the sequential minimum
      optimization-type decomposition method for support vector machines (SMO-SVM). It
      was implemented in parallel using MPI and C++ libraries and executed on both
      shared memory supercomputer and Linux cluster for multicategory classification of
      microarray data. PMC-SVM has been analyzed and evaluated using four microarray
      datasets with multiple diagnostic categories, such as different cancer types and
      normal tissue types. CONCLUSION: The experiments show that the PMC-SVM can
      significantly improve the performance of classification of microarray data
      without loss of accuracy, compared with previous work.

PMID- 17217508
TI  - Identification of new members of hydrophobin family using primary structure
      analysis.
AB  - BACKGROUND: Hydrophobins are fungal proteins that can turn into amphipathic
      membranes at hydrophilic/hydrophobic interfaces by self-assembly. The assemblages
      by Class I hydrophobins are extremely stable and possess the remarkable ability
      to change the polarity of the surface. One of its most important industrial
      applications is its usage as paint. Without detailed knowledge of the 3D
      structure and self-assembly principles of hydrophobins, it is difficult to make
      significant progress in furthering its research. RESULTS: In order to provide
      useful information to hydrophobin researchers, we analyzed primary structure of
      hydrophobins to gain more insight about these proteins. In this paper, we
      presented an in-depth primary sequence analysis using batch BLAST search of the
      database, sequence filtering by programming and motif finding by MEME. We used
      batch BLAST to find similar sequences in the NCBI nr database. Then we used MEME
      to find out motifs. Based on the newly found motifs and the well-known C-CC-C-C
      CC-C pattern we used MAST to search the entire nr database. At the end, domain
      search and phylogenetic analysis were conducted to confirm the result. After
      searching the nr database with the new PSSM-format motifs identified by MEME,
      many sequences from various species were found by MAST. Filtering process by
      pattern, domain and length left 9 qualified candidates. CONCLUSION: All of 9
      newly identified potential hydrophobins possess the common pattern and
      hydrophobin domain. From the multiple sequence alignment result, we can see that
      some of them are grouped very close to other known hydrophobins, which means
      their phylogenetic relationship is very close and it is highly plausible that
      they are indeed hydrophobin proteins.

PMID- 17217509
TI  - Evaluation of clustering algorithms for gene expression data.
AB  - BACKGROUND: Cluster analysis is an integral part of high dimensional data
      analysis. In the context of large scale gene expression data, a filtered set of
      genes are grouped together according to their expression profiles using one of
      numerous clustering algorithms that exist in the statistics and machine learning
      literature. A closely related problem is that of selecting a clustering algorithm
      that is "optimal" in some sense from a rather impressive list of clustering
      algorithms that currently exist. RESULTS: In this paper, we propose two
      validation measures each with two parts: one measuring the statistical
      consistency (stability) of the clusters produced and the other representing their
      biological functional congruence. Smaller values of these indices indicate better
      performance for a clustering algorithm. We illustrate this approach using two
      case studies with publicly available gene expression data sets: one involving a
      SAGE data of breast cancer patients and the other involving a time course cDNA
      microarray data on yeast. Six well known clustering algorithms UPGMA, K-Means,
      Diana, Fanny, Model-Based and SOM were evaluated. CONCLUSION: No single
      clustering algorithm may be best suited for clustering genes into functional
      groups via expression profiles for all data sets. The validation measures
      introduced in this paper can aid in the selection of an optimal algorithm, for a
      given data set, from a collection of available clustering algorithms.

PMID- 17217510
TI  - GenomeBlast: a web tool for small genome comparison.
AB  - BACKGROUND: Comparative genomics has become an essential approach for identifying
      homologous gene candidates and their functions, and for studying genome
      evolution. There are many tools available for genome comparisons. Unfortunately,
      most of them are not applicable for the identification of unique genes and the
      inference of phylogenetic relationships in a given set of genomes. RESULTS:
      GenomeBlast is a Web tool developed for comparative analysis of multiple small
      genomes. A new parameter called "coverage" was introduced and used along with
      sequence identity to evaluate global similarity between genes. With GenomeBlast,
      the following results can be obtained: (1) unique genes in each genome; (2)
      homologous gene candidates among compared genomes; (3) 2D plots of homologous
      gene candidates along the all pairwise genome comparisons; and (4) a table of
      gene presence/absence information and a genome phylogeny. We demonstrated the
      functions in GenomeBlast with an example of multiple herpesviral genome analysis
      and illustrated how GenomeBlast is useful for small genome comparison.
      CONCLUSION: We developed a Web tool for comparative analysis of small genomes,
      which allows the user not only to identify unique genes and homologous gene
      candidates among multiple genomes, but also to view their graphical distributions
      on genomes, and to reconstruct genome phylogeny. GenomeBlast runs on a Linux
      server with 4 CPUs and 4 GB memory. The online version of GenomeBlast is
      available to public by using a Web browser with the URL http://bioinfo
      srv1.awh.unomaha.edu/genomeblast/.

PMID- 17217511
TI  - Clustering of gene expression data: performance and similarity analysis.
AB  - BACKGROUND: DNA Microarray technology is an innovative methodology in
      experimental molecular biology, which has produced huge amounts of valuable data
      in the profile of gene expression. Many clustering algorithms have been proposed
      to analyze gene expression data, but little guidance is available to help choose
      among them. The evaluation of feasible and applicable clustering algorithms is
      becoming an important issue in today's bioinformatics research. RESULTS: In this
      paper we first experimentally study three major clustering algorithms:
      Hierarchical Clustering (HC), Self-Organizing Map (SOM), and Self Organizing Tree
      Algorithm (SOTA) using Yeast Saccharomyces cerevisiae gene expression data, and
      compare their performance. We then introduce Cluster Diff, a new data mining
      tool, to conduct the similarity analysis of clusters generated by different
      algorithms. The performance study shows that SOTA is more efficient than SOM
      while HC is the least efficient. The results of similarity analysis show that
      when given a target cluster, the Cluster Diff can efficiently determine the
      closest match from a set of clusters. Therefore, it is an effective approach for
      evaluating different clustering algorithms. CONCLUSION: HC methods allow a
      visual, convenient representation of genes. However, they are neither robust nor
      efficient. The SOM is more robust against noise. A disadvantage of SOM is that
      the number of clusters has to be fixed beforehand. The SOTA combines the
      advantages of both hierarchical and SOM clustering. It allows a visual
      representation of the clusters and their structure and is not sensitive to
      noises. The SOTA is also more flexible than the other two clustering methods. By
      using our data mining tool, Cluster Diff, it is possible to analyze the
      similarity of clusters generated by different algorithms and thereby enable
      comparisons of different clustering methods.

PMID- 17217512
TI  - Frequency distribution of TATA Box and extension sequences on human promoters.
AB  - BACKGROUND: TATA box is one of the most important transcription factor binding
      sites. But the exact sequences of TATA box are still not very clear. RESULTS: In
      this study, we conduct a dedicated analysis on the frequency distribution of TATA
      Box and its extension sequences on human promoters. Sixteen TATA elements derived
      from the TATA Box motif, TATAWAWN, are classified into three distribution
      patterns: peak, bottom-peak, and bottom. Fourteen TATA extension sequences are
      predicted to be the new TATA Box elements due to their high motif factors, which
      indicate their statistical significance. Statistical analysis on the promoters of
      mice, zebrafish and drosophila melanogaster verifies seven of these elements. It
      is also observed that the distribution of TATA elements on the promoters of
      housekeeping genes are very similar with their distribution on the promoters of
      tissue specific genes in human. CONCLUSION: The dedicated statistical analysis on
      TATA box and its extension sequences yields new TATA elements. The statistical
      significance of these elements has been verified on random data sets by
      calculating their p values.

PMID- 17217513
TI  - Particle simulation approach for subcellular dynamics and interactions of
      biological molecules.
AB  - BACKGROUND: Spatio-temporal dynamics within cells can now be visualized at
      appropriate resolution, due to the advances in molecular imaging technologies.
      Even single-particle tracking (SPT) and single fluorophore video imaging (SFVI)
      are now being applied to observation of molecular-level dynamics. However, little
      is known concerning how molecular-level dynamics affect properties at the
      cellular level. RESULTS: We propose an algorithm designed for three-dimensional
      simulation of the reaction-diffusion dynamics of molecules, based on a particle
      model. Chemical reactions proceed through the interactions of particles in space,
      with activation energies determining the rates of these chemical reactions at
      each interaction. This energy-based model can include the cellular membrane,
      membranes of other organelles, and cytoskeleton. The simulation algorithm was
      tested for a reversible enzyme reaction model and its validity was confirmed.
      Snapshot images taken from simulated molecular interactions on the cell-surface
      revealed clustering domains (size approximately 0.2 microm) associated with
      rafts. Sample trajectories of raft constructs exhibited "hop diffusion". These
      domains corralled the diffusive motion of membrane proteins. CONCLUSION: These
      findings demonstrate that our approach is promising for modelling the
      localization properties of biological phenomena.

PMID- 17217514
TI  - Combining comparative genomics with de novo motif discovery to identify human
      transcription factor DNA-binding motifs.
AB  - BACKGROUND: As more and more genomes are sequenced, comparative genomics
      approaches provide a methodology for identifying conserved regulatory elements
      that may be involved in gene regulations. RESULTS: We developed a novel method to
      combine comparative genomics with de novo motif discovery to identify human
      transcription factor binding motifs that are overrepresented and conserved in the
      upstream regions of a set of co-regulated genes. The method is validated by
      analyzing a well-characterized muscle specific gene set, and the results showed
      that our approach performed better than the existing programs in terms of
      sensitivity and prediction rate. CONCLUSION: The newly developed method can be
      used to extract regulatory signals in co-regulated genes, which can be derived
      from the microarray clustering analysis.

PMID- 17217515
TI  - Comparison of transcriptional responses in liver tissue and primary hepatocyte
      cell cultures after exposure to hexahydro-1, 3, 5-trinitro-1, 3, 5-triazine.
AB  - BACKGROUND: Cell culture systems are useful in studying toxicological effects of
      chemicals such as Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), however little
      is known as to how accurately isolated cells reflect responses of intact organs.
      In this work, we compare transcriptional responses in livers of Sprague-Dawley
      rats and primary hepatocyte cells after exposure to RDX to determine how
      faithfully the in vitro model system reflects in vivo responses. RESULTS:
      Expression patterns were found to be markedly different between liver tissue and
      primary cell cultures before exposure to RDX. Liver gene expression was enriched
      in processes important in toxicology such as metabolism of amino acids, lipids,
      aromatic compounds, and drugs when compared to cells. Transcriptional responses
      in cells exposed to 7.5, 15, or 30 mg/L RDX for 24 and 48 hours were different
      from those of livers isolated from rats 24 hours after exposure to 12, 24, or 48
      mg/Kg RDX. Most of the differentially expressed genes identified across
      conditions and treatments could be attributed to differences between cells and
      tissue. Some similarity was observed in RDX effects on gene expression between
      tissue and cells, but also significant differences that appear to reflect the
      state of the cell or tissue examined. CONCLUSION: Liver tissue and primary cells
      express different suites of genes that suggest they have fundamental differences
      in their cell physiology. Expression effects related to RDX exposure in cells
      reflected a fraction of liver responses indicating that care must be taken in
      extrapolating from primary cells to whole animal organ toxicity effects.

PMID- 17217516
TI  - Systematic gene function prediction from gene expression data by using a fuzzy
      nearest-cluster method.
AB  - BACKGROUND: Quantitative simultaneous monitoring of the expression levels of
      thousands of genes under various experimental conditions is now possible using
      microarray experiments. However, there are still gaps toward whole-genome
      functional annotation of genes using the gene expression data. RESULTS: In this
      paper, we propose a novel technique called Fuzzy Nearest Clusters for genome-wide
      functional annotation of unclassified genes. The technique consists of two steps:
      an initial hierarchical clustering step to detect homogeneous co-expressed gene
      subgroups or clusters in each possibly heterogeneous functional class; followed
      by a classification step to predict the functional roles of the unclassified
      genes based on their corresponding similarities to the detected functional
      clusters. CONCLUSION: Our experimental results with yeast gene expression data
      showed that the proposed method can accurately predict the genes' functions, even
      those with multiple functional roles, and the prediction performance is most
      independent of the underlying heterogeneity of the complex functional classes, as
      compared to the other conventional gene function prediction approaches.

PMID- 17217517
TI  - A novel approach to phylogenetic tree construction using stochastic optimization
      and clustering.
AB  - BACKGROUND: The problem of inferring the evolutionary history and constructing
      the phylogenetic tree with high performance has become one of the major problems
      in computational biology. RESULTS: A new phylogenetic tree construction method
      from a given set of objects (proteins, species, etc.) is presented. As an
      extension of ant colony optimization, this method proposes an adaptive
      phylogenetic clustering algorithm based on a digraph to find a tree structure
      that defines the ancestral relationships among the given objects. CONCLUSION: Our
      phylogenetic tree construction method is tested to compare its results with that
      of the genetic algorithm (GA). Experimental results show that our algorithm
      converges much faster and also achieves higher quality than GA.

PMID- 17217518
TI  - SVM Classifier - a comprehensive java interface for support vector machine
      classification of microarray data.
AB  - MOTIVATION: Graphical user interface (GUI) software promotes novelty by allowing
      users to extend the functionality. SVM Classifier is a cross-platform graphical
      application that handles very large datasets well. The purpose of this study is
      to create a GUI application that allows SVM users to perform SVM training,
      classification and prediction. RESULTS: The GUI provides user-friendly access to
      state-of-the-art SVM methods embodied in the LIBSVM implementation of Support
      Vector Machine. We implemented the java interface using standard swing libraries.
      We used a sample data from a breast cancer study for testing classification
      accuracy. We achieved 100% accuracy in classification among the BRCA1-BRCA2
      samples with RBF kernel of SVM. CONCLUSION: We have developed a java GUI
      application that allows SVM users to perform SVM training, classification and
      prediction. We have demonstrated that support vector machines can accurately
      classify genes into functional categories based upon expression data from DNA
      microarray hybridization experiments. Among the different kernel functions that
      we examined, the SVM that uses a radial basis kernel function provides the best
      performance. The SVM Classifier is available at http://mfgn.usm.edu/ebl/svm/.

PMID- 17217519
TI  - AffyMiner: mining differentially expressed genes and biological knowledge in
      GeneChip microarray data.
AB  - BACKGROUND: DNA microarrays are a powerful tool for monitoring the expression of
      tens of thousands of genes simultaneously. With the advance of microarray
      technology, the challenge issue becomes how to analyze a large amount of
      microarray data and make biological sense of them. Affymetrix GeneChips are
      widely used microarrays, where a variety of statistical algorithms have been
      explored and used for detecting significant genes in the experiment. These
      methods rely solely on the quantitative data, i.e., signal intensity; however,
      qualitative data are also important parameters in detecting differentially
      expressed genes. RESULTS: AffyMiner is a tool developed for detecting
      differentially expressed genes in Affymetrix GeneChip microarray data and for
      associating gene annotation and gene ontology information with the genes
      detected. AffyMiner consists of the functional modules, GeneFinder for detecting
      significant genes in a treatment versus control experiment and GOTree for mapping
      genes of interest onto the Gene Ontology (GO) space; and interfaces to run
      Cluster, a program for clustering analysis, and GenMAPP, a program for pathway
      analysis. AffyMiner has been used for analyzing the GeneChip data and the results
      were presented in several publications. CONCLUSION: AffyMiner fills an important
      gap in finding differentially expressed genes in Affymetrix GeneChip microarray
      data. AffyMiner effectively deals with multiple replicates in the experiment and
      takes into account both quantitative and qualitative data in identifying
      significant genes. AffyMiner reduces the time and effort needed to compare data
      from multiple arrays and to interpret the possible biological implications
      associated with significant changes in a gene's expression.

PMID- 17217520
TI  - In silico modelling of hormone response elements.
AB  - BACKGROUND: An important step in understanding the conditions that specify gene
      expression is the recognition of gene regulatory elements. Due to high diversity
      of different types of transcription factors and their DNA binding preferences, it
      is a challenging problem to establish an accurate model for recognition of
      functional regulatory elements in promoters of eukaryotic genes. RESULTS: We
      present a method for precise prediction of a large group of transcription factor
      binding sites - steroid hormone response elements. We use a large training set of
      experimentally confirmed steroid hormone response elements, and adapt a sequence
      based statistic method of position weight matrix, for identification of the
      binding sites in the query sequences. To estimate the accuracy level, a table of
      correspondence of sensitivity vs. specificity values is constructed from a number
      of independent tests. Furthermore, feed-forward neural network is used for cross
      verification of the predicted response elements on genomic sequences. CONCLUSION:
      The proposed method demonstrates high accuracy level, and therefore can be used
      for prediction of hormone response elements de novo. Experimental results support
      our analysis by showing significant improvement of the proposed method over
      previous HRE recognition methods.

PMID- 17217521
TI  - An improved ant colony algorithm with diversified solutions based on the immune
      strategy.
AB  - BACKGROUND: Ant colony algorithm has emerged recently as a new meta-heuristic
      method, which is inspired from the behaviours of real ants for solving NP-hard
      problems. However, the classical ant colony algorithm also has its defects of
      stagnation and premature. This paper aims at remedying these problems. RESULTS:
      In this paper, we propose an adaptive ant colony algorithm that simulates the
      behaviour of biological immune system. The solutions of the problem are much more
      diversified than traditional ant colony algorithms. CONCLUSION: The proposed
      method for improving the performance of traditional ant colony algorithm takes
      into account the polarization of the colonies, and adaptively adjusts the
      distribution of the solutions obtained by the ants. This makes the solutions more
      diverse so as to avoid the stagnation and premature phenomena.

PMID- 17217522
TI  - A fast parallel algorithm for finding the longest common sequence of multiple
      biosequences.
AB  - BACKGROUND: Searching for the longest common sequence (LCS) of multiple
      biosequences is one of the most fundamental tasks in bioinformatics. In this
      paper, we present a parallel algorithm named FAST_LCS to speedup the computation
      for finding LCS. RESULTS: A fast parallel algorithm for LCS is presented. The
      algorithm first constructs a novel successor table to obtain all the identical
      pairs and their levels. It then obtains the LCS by tracing back from the
      identical character pairs at the last level. Effective pruning techniques are
      developed to significantly reduce the computational complexity. Experimental
      results on gene sequences in the tigr database show that our algorithm is optimal
      and much more efficient than other leading LCS algorithms. CONCLUSION: We have
      developed one of the fastest parallel LCS algorithms on an MPP parallel computing
      model. For two sequences X and Y with lengths n and m, respectively, the memory
      required is max{4*(n+1)+4*(m+1), L}, where L is the number of identical character
      pairs. The time complexity is O(L) for sequential execution, and O(|LCS(X, Y)|)
      for parallel execution, where |LCS(X, Y)| is the length of the LCS of X and Y.
      For n sequences X1, X2, ..., Xn, the time complexity is O(L) for sequential
      execution, and O(|LCS(X1, X2, ..., Xn)|) for parallel execution. Experimental
      results support our analysis by showing significant improvement of the proposed
      method over other leading LCS algorithms.

PMID- 17217523
TI  - Estimate haplotype frequencies in pedigrees.
AB  - BACKGROUND: Haplotype analysis has gained increasing attention in the context of
      association studies of disease genes and drug responsivities over the last years.
      The potential use of haplotypes has led to the initiation of the HapMap project
      which is to investigate haplotype patterns in the human genome in different
      populations. Haplotype inference and frequency estimation are essential
      components of this endeavour. RESULTS: We present a two-stage method to estimate
      haplotype frequencies in pedigrees, which includes haplotyping stage and
      estimation stage. In the haplotyping stage, we propose a linear time algorithm to
      determine all zero-recombinant haplotype configurations for each pedigree. In the
      estimation stage, we use the expectation-maximization (EM) algorithm to estimate
      haplotype frequencies based on these haplotype configurations. The experiments
      demonstrate that our method runs much faster and gives more credible estimates
      than other popular haplotype analysis software that discards the pedigree
      information. CONCLUSION: Our method suggests that pedigree information is of
      great importance in haplotype analysis. It can be used to speedup estimation
      process, and to improve estimation accuracy as well. The result also demonstrates
      that the whole haplotype configuration space can be substituted by the space of
      zero-recombinant haplotype configurations in haplotype frequency estimation,
      especially when the considered haplotype block is relatively short.

PMID- 17217524
TI  - Maximum common subgraph: some upper bound and lower bound results.
AB  - BACKGROUND: Structure matching plays an important part in understanding the
      functional role of biological structures. Bioinformatics assists in this effort
      by reformulating this process into a problem of finding a maximum common subgraph
      between graphical representations of these structures. Among the many different
      variants of the maximum common subgraph problem, the maximum common induced
      subgraph of two graphs is of special interest. RESULTS: Based on current research
      in the area of parameterized computation, we derive a new lower bound for the
      exact algorithms of the maximum common induced subgraph of two graphs which is
      the best currently known. Then we investigate the upper bound and design
      techniques for approaching this problem, specifically, reducing it to one of
      finding a maximum clique in the product graph of the two given graphs.
      Considering the upper bound result, the derived lower bound result is
      asymptotically tight. CONCLUSION: Parameterized computation is a viable approach
      with great potential for investigating many applications within bioinformatics,
      such as the maximum common subgraph problem studied in this paper. With an
      improved hardness result and the proposed approaches in this paper, future
      research can be focused on further exploration of efficient approaches for
      different variants of this problem within the constraints imposed by real
      applications.

PMID- 17217525
TI  - FM-test: a fuzzy-set-theory-based approach to differential gene expression data
      analysis.
AB  - BACKGROUND: Microarray techniques have revolutionized genomic research by making
      it possible to monitor the expression of thousands of genes in parallel. As the
      amount of microarray data being produced is increasing at an exponential rate,
      there is a great demand for efficient and effective expression data analysis
      tools. Comparison of gene expression profiles of patients against those of normal
      counterpart people will enhance our understanding of a disease and identify leads
      for therapeutic intervention. RESULTS: In this paper, we propose an innovative
      approach, fuzzy membership test (FM-test), based on fuzzy set theory to identify
      disease associated genes from microarray gene expression profiles. A new concept
      of FM d-value is defined to quantify the divergence of two sets of values. We
      further analyze the asymptotic property of FM-test, and then establish the
      relationship between FM d-value and p-value. We applied FM-test to a diabetes
      expression dataset and a lung cancer expression dataset, respectively. Within the
      10 significant genes identified in diabetes dataset, six of them have been
      confirmed to be associated with diabetes in the literature and one has been
      suggested by other researchers. Within the 10 significantly overexpressed genes
      identified in lung cancer data, most (eight) of them have been confirmed by the
      literatures which are related to the lung cancer. CONCLUSION: Our experiments on
      synthetic datasets show that FM-test is effective and robust. The results in
      diabetes and lung cancer datasets validated the effectiveness of FM-test. FM-test
      is implemented as a Web-based application and is available for free at
      http://database.cs.wayne.edu/bioinformatics.

PMID- 17217526
TI  - The impact of sample imbalance on identifying differentially expressed genes.
AB  - BACKGROUND: Recently several statistical methods have been proposed to identify
      genes with differential expression between two conditions. However, very few
      studies consider the problem of sample imbalance and there is no study to
      investigate the impact of sample imbalance on identifying differential expression
      genes. In addition, it is not clear which method is more suitable for the
      unbalanced data. RESULTS: Based on random sampling, two evaluation models are
      proposed to investigate the impact of sample imbalance on identifying
      differential expression genes. Using the proposed evaluation models, the
      performances of six famous methods are compared on the unbalanced data. The
      experimental results indicate that the sample imbalance has a great influence on
      selecting differential expression genes. Furthermore, different methods have very
      different performances on the unbalanced data. Among the six methods, the welch t
      test appears to perform best when the size of samples in the large variance group
      is larger than that in the small one, while the Regularized t-test and SAM
      outperform others on the unbalanced data in other cases. CONCLUSION: Two proposed
      evaluation models are effective and sample imbalance should be taken into account
      in microarray experiment design and gene expression data analysis. The results
      and two proposed evaluation models can provide some help in selecting suitable
      method to process the unbalanced data.

PMID- 17217527
TI  - Degenerated primer design to amplify the heavy chain variable region from
      immunoglobulin cDNA.
AB  - BACKGROUND: The amplification of variable regions of immunoglobulins has become a
      major challenge in the cloning of antibody genes, whether from hybridoma cell
      lines or splenic B cells. Using conventional protocols, the heavy-chain variable
      region genes often are not amplified successfully from the hybridoma cell lines.
      RESULTS: A novel method was developed to design the degenerated primer of
      immunoglobulin cDNA and to amplify cDNA ends rapidly. Polymerase chain reaction
      protocols were performed to recognize the VH gene from the hybridoma cell line.
      The most highly conserved region in the middle of the VH regions of the Ig cDNA
      was identified, and a degenerated 5'primer was designed, using our algorithms.
      The VH gene was amplified by both the 3'RACE and 5'RACE. The VH sequence of CSA
      cells was 399 bp. CONCLUSION: The new protocol rescued the amplifications of the
      VH gene that had failed under conventional protocols. In addition, there was a
      notable increase in amplification specificity. Moreover, the algorithm improved
      the primer design efficiency and was shown to be useful both for building VH and
      VL gene libraries and for the cloning of unknown genes in gene families.

PMID- 17217528
TI  - Anterior anal sphincter repair can be of long term benefit: a 12-year case cohort
      from a single surgeon.
AB  - BACKGROUND: Early surgical results of anterior sphincter repair for faecal
      incontinence can be good, but in the longer term are often disappointing. This
      study aimed to determine the short and long term outcomes from anterior sphincter
      repair and identify factors predictive of long term success. METHODS: Patients
      who underwent anterior sphincter repair between 1989 and 2001 in one institution
      were identified. Postal questionnaires were sent to patients, which included
      validated scoring systems for symptom severity and quality of life assessments
      for faecal incontinence. Patient demographics and risk factors were recorded as
      were the results of anorectal physiology studies and endoanal ultrasound.
      RESULTS: Eighty-five patients underwent repair by one consultant. The length of
      follow up ranged from 1 to 12 years. Most patients (96%) had early symptom
      improvement postoperatively. Of the 47 patients assessed long term (> or = 5
      years), 28 (60%) maintained this success. Significant improvements in quality of
      life were observed (P < 0.001). Neither patient, surgical nor anorectal
      physiology study parameters were predictive of outcome. CONCLUSION: There were no
      predictive factors of outcome success and no changes in anal manometry
      identified, however anterior sphincter repair remains worthwhile. Changes in
      compliance of the anorectum may be responsible for symptom improvement.

PMID- 17217529
TI  - Factors influencing the outcome of paediatric cardiac surgical patients during
      extracorporeal circulatory support.
AB  - BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (ECMO) is a common
      modality of circulatory assist device used in children. We assessed the outcome
      of children who had ECMO following repair of congenital cardiac defects (CCD) and
      identified the risk factors associated with hospital mortality. METHODS: From
      April 1990 to December 2003, 53 patients required ECMO following surgical
      correction of CCD. Retrospectively collected data was analyzed with univariate
      and multivariate logistic regression analysis. RESULTS: Median age and weight of
      the patients were 150 days and 5.4 kgs respectively. The indications for ECMO
      were low cardiac output in 16, failure to wean cardiopulmonary bypass in 13,
      cardiac arrest in 10 and cardio-respiratory failure in 14 patients. The mean
      duration of ECMO was 143 hours. Weaning off from ECMO was successful in 66% and
      of these 83% were survival to hospital-discharge. 37.7% of patients were alive
      for the mean follow-up period of 75 months. On univariate analysis, arrhythmias,
      ECMO duration >168 hours, bleeding complications, renal replacement therapy on
      ECMO, arrhythmias and cardiac arrest after ECMO were associated with hospital
      mortality.On multivariate analysis, abnormal neurology, bleeding complications
      and arrhythmias after ECMO were associated with hospital mortality. Extra and
      intra-thoracic cannulations were used in 79% and 21% of patients respectively and
      extra-thoracic cannulation had significantly less bleeding complications (p =
      0.031). CONCLUSION: ECMO provides an effective circulatory support following
      surgical repair of CCD in children. Extra-thoracic cannulation is associated with
      less bleeding complications. Abnormal neurology, bleeding complications on ECMO
      and arrhythmias after ECMO are poor prognostic indicators for hospital survival.

PMID- 17217530
TI  - The role of PDGF in radiation oncology.
AB  - Platelet-derived growth factor (PDGF) was originally identified as a constituent
      of blood serum and subsequently purified from human platelets. PDGF ligand is a
      dimeric molecule consisting of two disulfide-bonded chains from A-, B-, C- and D
      polypeptide chains, which combine to homo- and heterodimers. The PDGF isoforms
      exert their cellular effects by binding to and activating two structurally
      related protein tyrosine kinase receptors. PDGF is a potent mitogen and
      chemoattractant for mesenchymal cells and also a chemoattractant for neutrophils
      and monocytes. In radiation oncology, PDGF are important for several pathologic
      processes, including oncogenesis, angiogenesis and fibrogenesis. Autocrine
      activation of PDGF was observed and interpreted as an important mechanism
      involved in brain and other tumors. PDGF has been shown to be fundamental for the
      stability of normal blood vessel formation, and may be essential for the
      angiogenesis in tumor tissue. PDGF also plays an important role in the
      proliferative disease, such as atherosclerosis and radiation-induced fibrosis,
      regarding its proliferative stimulation of fibroblast cells. Moreover, PDGF was
      also shown to stimulate production of extracellular matrix proteins, which are
      mainly responsible for the irreversibility of these diseases. This review
      introduces the structural and functional properties of PDGF and PDGF receptors
      and discusses the role and mechanism of PDGF signaling in normal and tumor
      tissues under different conditions in radiation oncology.

PMID- 17217531
TI  - Diet, physical activity, and adiposity in children in poor and rich
      neighbourhoods: a cross-sectional comparison.
AB  - BACKGROUND: Obesity in Canadian children increased three-fold in twenty years.
      Children living in low-income neighborhoods exercise less and are more overweight
      than those living in more affluent neighborhoods after accounting for family
      socio-economic status. Strategies to prevent obesity in children have focused on
      personal habits, ignoring neighborhood characteristics. It is essential to
      evaluate diet and physical activity patterns in relation to socio-economic
      conditions to understand the determinants of obesity. The objective of this pilot
      study was to compare diet, physical activity, and the built environment in two
      Hamilton area elementary schools serving socio-economically different
      communities. METHODS: We conducted a cross-sectional study (November 2005-March
      2006) in two public elementary schools in Hamilton, Ontario, School A and School
      B, located in low and high socioeconomic areas respectively. We assessed dietary
      intake, physical activity, dietary restraint, and anthropometric measures in
      consenting children in grades 1 and higher. From their parents we assessed family
      characteristics and walkability of the built environment. RESULTS: 160 children
      (n = 48, School A and n = 112, School B), and 156 parents (n = 43, School A and n
      = 113, School B) participated in this study. The parents with children at School
      A were less educated and had lower incomes than those at School B. The School A
      neighborhood was perceived to be less walkable than the School B neighborhood.
      Children at School A consumed more baked foods, chips, sodas, gelatin desserts,
      and candies and less low fat dairy, and dark bread than those at School B.
      Children at School A watched more television and spent more time in front of the
      computer than children studying at School B, but reported spending less time
      sitting on weekdays and weekends. Children at both schools were overweight but
      there was no difference in their mean BMI z-scores (School A = 0.65 versus School
      B = 0.81, p-value = 0.38). CONCLUSION: The determinants of overweight in children
      may be more complex than imagined. In future intervention programs researchers
      may consider addressing environmental factors, and customizing lifestyle
      interventions so that they are closer to community needs.

PMID- 17217532
TI  - Mutations in the TPsiC loop of E. coli tRNALys,3 have varied effects on in trans
      complementation of HIV-1 replication.
AB  - BACKGROUND: Human immunodeficiency virus (HIV-1) exclusively selects and utilizes
      tRNALys,3 as the primer for initiation of reverse transcription. Several elements
      within the TPsiC stem loop of tRNALys,3 are postulated to be important for
      selection and use in reverse transcription. The post-transcriptional modification
      at nucleotide 58 could play a role during plus-strand synthesis to stop reverse
      transcriptase from re-copying the tRNA primer. Nucleotides 53 and 54 within the
      TPsiC stem loop of the tRNA have been shown to be important to form the complex
      between tRNA and the HIV-1 viral genome during initiation of reverse
      transcription. RESULTS: To further delineate the features of the TPsiC stem loop
      of tRNALys,3 in reverse transcription, we have developed a complementation system
      in which E. coli tRNALys,3 is provided in trans to an HIV-1 genome in which the
      PBS is complementary to this tRNA. Successful selection and use of E. coli
      tRNALys,3 results in the production of infectious virus. We have used this single
      round infectious system to ascertain the effects that different mutants in the
      TPsiC stem loop of tRNALys,3 have on complementation. Mutants were designed
      within the TPsiC loop (nucleotide 58) and within the stem and loop of the TPsiC
      loop (nucleotides 53 and 54). Analysis of the expression of E. coli tRNALys,3
      mutants revealed differences in the capacity for aminoacylation, which is an
      indication of intracellular stability of the tRNA. Alteration of nucleotide 58
      from A to U (A58U), T54G and TG5453CC all resulted in tRNALys,3 that was
      aminoacylated when expressed in cells, while a T54C mutation resulted in a
      tRNALys,3 that was not aminoacylated. Both the A58U and T54G mutated tRNALys,3
      complemented HIV-1 replication similar to wild type E. coli tRNALys,3. In
      contrast, the TG5453CC tRNALys,3 mutant did not complement replication.
      CONCLUSION: The results demonstrate that post-transcriptional modification of
      nucleotide 58 in tRNALys,3 is not essential for HIV-1 reverse transcription. In
      contrast, nucleotides 53 and 54 of tRNALys,3 are important for aminoacylation and
      selection and use of the tRNALys,3 in reverse transcription.

PMID- 17217533
TI  - Molecular analysis of hepatitis B virus "a" determinant in asymptomatic and
      symptomatic Mexican carriers.
AB  - BACKGROUND: Hepatitis B virus (HBV) is a small DNA-containing virus with 4 genes,
      C, S, X and P. The S gene codes for the surface antigen (HBsAg), which contains
      the "a" determinant, the main region for induction of a protective humoral immune
      response. To compare the genotype and sequence of the "a" determinant between
      strains isolated from asymptomatic and symptomatic Mexican HBV carriers. RESULTS:
      21 asymptomatic (blood donors) and 12 symptomatic (with clinical signs and with
      >1 year lamivudine treatment) HBV carriers were studied; all patients were
      positive for the HBsAg in serum. Viral load, genotypes, and subtypes were
      determined in plasma. A fragment of the S gene including the "a" determinant was
      PCR amplified and sequenced to determine genotype, subtype and to identify
      mutations. Mean viral load was 0.7965 x 104 copies/ml in asymptomatic carriers
      and 2.73 x 106 copies/ml in symptomatic patients. Genotypes H, C, and F were
      identified in asymptomatic individuals; whereas H was dominant in symptomatic
      patients. A fragment of 279 bp containing the "a" determinant was amplified from
      all 33 carriers and sequences aligned with S gene sequences in the GenBank.
      Mutations identified were Y100N, T126I, Q129H and N146K in the asymptomatic
      group, and F93I and A128V in the symptomatic group. CONCLUSION: Differences in
      genotype and in mutations in the "a" determinant were found between strains from
      asymptomatic and symptomatic HBV Mexican carriers.

PMID- 17217534
TI  - Exploring the effects of telehealth on medical human resources supply: a
      qualitative case study in remote regions.
AB  - BACKGROUND: The availability of medical human resource supply is a growing
      concern for rural and remote communities in many countries. In the last decade,
      various telehealth experiences in Canada have highlighted the potential impact of
      this technology on professional practice. The purpose of this study was to
      explore physicians' and managers' perceptions regarding the potential of
      telehealth to support recruitment and retention of physicians in remote and rural
      regions. METHODS: A case study in Eastern Quebec was performed to explore this
      complex phenomenon. The analytical framework was based on two literature reviews
      and a Delphi study. Data were collected from semi-structured interviews with 41
      physicians and 22 managers. Transcripts were produced and interview content was
      coded independently by two judges and validated by an expert panel. RESULTS:
      Interviews have highlighted the potential impact of telehealth on several factors
      influencing the recruitment and retention of physicians in rural and remote
      regions. The potential effects of telehealth on physicians' choice of practice
      location could be seen at the professional, organizational, educational and
      individual levels. For instance, telehealth could improve work satisfaction by
      allowing a regional on-call duty system and a better follow-up of patients.
      However, there are also certain limits related to telehealth, such as the fear
      that it would eventually replace all continuing medical education activities and
      onsite specialists in remoteregions. CONCLUSION: Telehealth is likely to have an
      impact on several factors related to medical workforce supply in remote and rural
      regions. However, the expected benefits will materialize if and only if this
      technology is properly integrated into organizations as a support to professional
      practice.

PMID- 17217535
TI  - Specification of primordial germ cells in medaka (Oryzias latipes).
AB  - BACKGROUND: Primordial germ cells (PGCs) give rise to gametes that are
      responsible for the development of a new organism in the next generation. Two
      modes of germ line specification have been described: the inheritance of
      asymmetrically-localized maternally provided cytoplasmic determinants and the
      induction of the PGC fate by other cell types. PGCs specification in zebrafish
      appears to depend on inheritance of germ plasm in which several RNA molecules
      such as vasa and nanos reside. Whether the specification mode of PGCs found in
      zebrafish is general for other fish species was brought into question upon
      analysis of olvas expression--the vasa homologue in another teleost, medaka
      (Oryzias latipes). Here, in contrast to the findings in zebrafish, the PGCs are
      found in a predictable position relative to a somatic structure, the embryonic
      shield. This finding, coupled with the fact that vasa mRNA, which is localized to
      the germ plasm of zebrafish but does not label a similar structure in medaka
      opened the possibility of fundamentally different mechanisms governing PGC
      specification in these two fish species. RESULTS: In this study we addressed the
      question concerning the mode of PGC specification in medaka using embryological
      experiments, analysis of RNA stability in the PGCs and electron microscopy
      observations. Dramatic alterations in the somatic environment, i.e. induction of
      a secondary axis or mesoderm formation alteration, did not affect the PGC number.
      Furthermore, the PGCs of medaka are capable of protecting specific RNA molecules
      from degradation and could therefore exhibit a specific mRNA expression pattern
      controlled by posttrancriptional mechanisms. Subsequent analysis of 4-cell stage
      medaka embryos using electron microscopy revealed germ plasm-like structures
      located at a region corresponding to that of zebrafish germ plasm. CONCLUSION:
      Taken together, these results are consistent with the idea that in medaka the
      inheritance of maternally provided asymmetrically-localized cytoplasmic
      determinants directs cells to assume the germ line fate similar to zebrafish
      PGCs.

PMID- 17217536
TI  - Glutathione S-transferase genotypes modify lung function decline in the general
      population: SAPALDIA cohort study.
AB  - BACKGROUND: Understanding the environmental and genetic risk factors of
      accelerated lung function decline in the general population is a first step in a
      prevention strategy against the worldwide increasing respiratory pathology of
      chronic obstructive pulmonary disease (COPD). Deficiency in antioxidative and
      detoxifying Glutathione S-transferase (GST) gene has been associated with poorer
      lung function in children, smokers and patients with respiratory diseases. In the
      present study, we assessed whether low activity variants in GST genes are also
      associated with accelerated lung function decline in the general adult
      population. METHODS: We examined with multiple regression analysis the
      association of polymorphisms in GSTM1, GSTT1 and GSTP1 genes with annual decline
      in FEV1, FVC, and FEF25-75 during 11 years of follow-up in 4686 subjects of the
      prospective SAPALDIA cohort representative of the Swiss general population.
      Effect modification by smoking, gender, bronchial hyperresponisveness and age was
      studied. RESULTS: The associations of GST genotypes with FEV1, FVC, and FEF25-75
      were comparable in direction, but most consistent for FEV1. GSTT1 homozygous gene
      deletion alone or in combination with GSTM1 homozygous gene deletion was
      associated with excess decline in FEV1 in men, but not women, irrespective of
      smoking status. The additional mean annual decline in FEV1 in men with GSTT1 and
      concurrent GSTM1 gene deletion was -8.3 ml/yr (95% confidence interval: -12.6 to 
      3.9) relative to men without these gene deletions. The GSTT1 effect on the FEV1
      decline comparable to the observed difference in FEV1 decline between never and
      persistent smoking men. Effect modification by gender was statistically
      significant. CONCLUSION: Our results suggest that genetic GSTT1 deficiency is a
      prevalent and strong determinant of accelerated lung function decline in the male
      general population.

PMID- 17217537
TI  - A single institution experience of combined modality management of extra skeletal
      Ewings sarcoma.
AB  - BACKGROUND: Extraskeletal Ewings sarcoma are rare tumors for which there is no
      consensus on optimal management. METHODS: A retrospective review of the clinical
      features, treatment and outcome of patients with extraskeletal Ewings sarcoma who
      reported to a single institution between January 1992-December 2003 is reported.
      RESULTS: A total of 19 patients with extraskeletal Ewings sarcoma were
      identified. Of these, 4 patients had metastatic disease at presentation and 15
      patients with non-metastatic disease received combined modality treatment with
      primary combination chemotherapy followed by local treatment with radiotherapy or
      surgery. Disease free survival and overall survival for patients with non
      metastatic disease after combined modality treatment were 60% and 30%
      respectively. The significant predictors for prolonged disease free survival and
      overall survival were high haemoglobin (p = 0.002), low lactate dehydrogenase (p
      = 0.028), chemotherapy with Vincristine, Adriamycin, Cyclophosphamide, Ifosfamide
      and Etoposide regime (p = 0.008) and complete response to chemotherapy (p =
      0.001). CONCLUSION: Aggressive combination chemotherapy followed by complete
      surgery or radiotherapy to a dose of more than 50 Gy is essential to confer
      optimal outcome for patients with extraskeletal Ewings sarcoma.

PMID- 17217538
TI  - Variation in heart rate influences the assessment of transient ischemic dilation
      in myocardial perfusion scintigraphy.
AB  - BACKGROUND: Transient arrhythmias can affect transient ischemic dilation (TID)
      ratios. This study was initiated to evaluate the frequency and effect of normal
      heart rate change on TID measures in routine clinical practice. METHODS:
      Consecutive patients undergoing stress/rest sestamibi gated myocardial perfusion
      scintigraphy were studied (N = 407). Heart rate at the time of stress and rest
      imaging were recorded. TID ratios were analyzed in relation to absolute change in
      heart rate (stress minus rest) for subjects with normal perfusion and systolic
      function (Group 1, N = 169) and those with abnormalities in perfusion and/or
      function (Group 2, N = 238). RESULTS: In Group 1, mean TID ratio was inversely
      correlated with the change in heart rate (r = -0.47, P < 0.0001). For every
      increase of 10 BPM in heart rate change, the TID ratio decreased by approximately
      0.06 (95% confidence interval 0.04-0.07). In Group 2, multiple linear regression
      demonstrated that the change in heart rate (beta = -0.25, P < 0.0001) and the
      summed difference score (beta = 0.36, P < 0.0001) were independent predictors of
      the TID ratio. CONCLUSION: Normal variation in heart rate between the stress and
      rest components of myocardial perfusion scans is common and can influence TID
      ratios in patients with normal and abnormal cardiac scans.

PMID- 17217539
TI  - Understanding cultural significance, the edible mushrooms case.
AB  - BACKGROUND: Cultural significance is a keystone in quantitative ethnobiology,
      which offers the possibility to make inferences about traditional nomenclature
      systems, use, appropriation and valuing of natural resources. In the present
      work, using as model the traditional mycological knowledge of Zapotecs from
      Oaxaca, Mexico, we analyze the cultural significance of wild edible resources.
      METHODS: In 2003 we applied 95 questionnaires to a random sample of informants.
      With this data we integrated the Edible Mushroom Cultural Significance Index.
      This index included eight variables: frequency of mention, perceived abundance,
      use frequency, taste, multifunctional food use, knowledge transmission, health
      and economy. Data were analyzed in an inductive perspective using ordination and
      grouping techniques to reveal the behavior of species in a cultural multivariate
      dimension. RESULTS: In each variable the species had different conducts.
      Cantharellus cibarius s.l. was the species with most frequency of mention.
      Pleurotus sp. had the highest perceived abundance. C. cibarius s.l. was the most
      frequently consumed species. Gomphus clavatus was the most palatable species and
      also ranked highest in the multifunctional food index. Cortinarius secc. Malacii
      sp. had the highest traditional importance. Only Tricholoma magnivelare was
      identified as a health enhancer. It also had the most economic importance.
      According to the compound index, C. cibarius s.l., the Amanita caesarea complex,
      Ramaria spp. and Neolentinus lepideus were the mushrooms with highest cultural
      significance. Multivariate analysis showed that interviewees identify three main
      groups of mushrooms: species with high traditional values, frequent consumption
      and known by the majority; species that are less known, infrequently consumed and
      without salient characteristics; and species with low traditional values, with
      high economic value and health enhancers. CONCLUSION: The compound index divided
      the cultural significance into several cultural domains and showed the causes
      that underlie this phenomenon. This approach can be used in cross-cultural
      studies because it brings a list with the relative position of species among a
      cultural significance gradient. This list is suitable for comparisons and also it
      is flexible because cultural variables can be included or removed to adjust it to
      the nature of the different cultures or resources under study.

PMID- 17217540
TI  - Basal-like grade III invasive ductal carcinoma of the breast: patterns of
      metastasis and long-term survival.
AB  - INTRODUCTION: Cytokeratin (CK) 14, one of several markers expressed in normal
      myoepithelial/basal cells, is also expressed in a proportion of breast
      carcinomas. Previous studies have suggested that expression of such 'basal'
      markers predicts different biological behaviour, with more frequent lung and
      brain metastases and poorer prognosis than other carcinomas. METHODS: We
      performed CK14 immunohistochemistry on 443 grade III invasive ductal carcinomas
      with extended clinical follow-up (mean 116 months), and we correlated CK14
      immunopositivity (basal-like phenotype) with clinicopathological criteria.
      RESULTS: Eighty-eight of 443 (20%) tumours showed CK14 expression. CK14-positive
      tumours were more likely to be oestrogen receptor-negative (p < 0.0001) and
      axillary node-negative (p = 0.001) than were CK14-negative cases. CK14-positive
      cases developed less bone and liver metastases (hazard ratio [HR] 0.49, p = 0.01,
      and HR 0.53, p = 0.035, respectively) but more frequent brain metastases (HR
      1.92, p = 0.051). In patients without metastatic disease, disease-free survival
      in CK14-positive cases was significantly better than in CK14-negative cases (HR
      0.65, p = 0.005). In patients with metastatic disease, however, CK14 positivity
      was associated with a poorer prognosis (HR 1.84, p = 0.001). The overall survival
      in CK14-positive and -negative patients was similar at 5 years (60% and 59%,
      respectively), but the long-term survival was better in CK14-positive patients
      (HR 0.69, p = 0.02). CONCLUSION: These results demonstrate that basal-like
      tumours differ in their biological behaviour from other tumours, with a distinct
      pattern of metastatic spread. Compared to other grade III tumours, basal-like
      tumours appear to have a relatively good long-term survival but survival after
      metastases is poor.

PMID- 17217541
TI  - Qualitative network models and genome-wide expression data define carbon/nitrogen
      responsive molecular machines in Arabidopsis.
AB  - BACKGROUND: Carbon (C) and nitrogen (N) metabolites can regulate gene expression
      in Arabidopsis thaliana. Here, we use multi-network analysis of microarray data
      to identify molecular networks regulated by C and N in the Arabidopsis root
      system. RESULTS: We used the Arabidopsis whole genome Affymetrix gene chip to
      explore global gene expression responses in plants exposed transiently to a
      matrix of C and N treatments. We used ANOVA analysis to define quantitative
      models of regulation for all detected genes. Our results suggest that about half
      of the Arabidopsis transcriptome is regulated by C, N or CN interactions. We
      found ample evidence for interactions between C and N that include genes involved
      in metabolic pathways, protein degradation and auxin signaling. To provide a
      global, yet detailed, view of how the cell molecular network is adjusted in
      response to the CN treatments, we constructed a qualitative multi-network model
      of the Arabidopsis metabolic and regulatory molecular network, including 6,176
      genes, 1,459 metabolites and 230,900 interactions among them. We integrated the
      quantitative models of CN gene regulation with the wiring diagram in the multi
      network, and identified specific interacting genes in biological modules that
      respond to C, N or CN treatments. CONCLUSION: Our results indicate that CN
      regulation occurs at multiple levels, including potential post-transcriptional
      control by microRNAs. The network analysis of our systematic dataset of CN
      treatments indicates that CN sensing is a mechanism that coordinates the global
      and coordinated regulation of specific sets of molecular machines in the plant
      cell.

PMID- 17217542
TI  - The effect of gender, age, and geographical location on the incidence and
      prevalence of renal replacement therapy in Wales.
AB  - BACKGROUND: This study used a cross sectional survey to examine the effect of
      gender, age, and geographical location on the population prevalence of renal
      replacement therapy (RRT) provision in Wales. METHODS: Physicians in renal
      centres in Wales and in adjacent areas of England were asked to undertake a
      census of patients on renal replacement therapy on 30 June 2004 using an agreed
      protocol. Data were collated and analysed in anonymous form. RESULTS: 2434
      patients were on RRT in Wales at the census date. Median age of patients on RRT
      was 56 years, peritoneal dialysis 58 years, haemodialysis 66 years and
      transplantation 50 years. The three treatment modalities had significantly
      different age-specific peak prevalence rates and distributions. RRT age-specific
      prevalence rates peaked at around 70 years (1790 pmp), transplantation at around
      60 years (924 pmp), haemodialysis at around 80 years (1080 pmp) and peritoneal
      dialysis did not have a clear peak prevalence rate. Age-specific incidence of RRT
      peaked at a rate of 488 pmp at 79 years, as did incidence rates for
      haemodialysis, which peaked at the same age. Age had less effect on the
      initiation of peritoneal dialysis, which had a broad plateau between the early
      fifties and late seventies. Kidney transplantation rates were highest in the
      early fifties but were markedly absent in old age. CONCLUSION: Differences in the
      provision of RRT are evident, particularly in the very elderly, where the gender
      difference for haemodialysis is particularly marked. The study illustrates that
      grouping patients over 75 years into a single age-band may mask significant
      diversity within this age group. Significant numbers of very elderly patients who
      are currently not receiving RRT may wish to receive RRT as the elderly population
      increases, and as technology improves survival and quality of life on RRT. The
      study suggests that if technologies that are more effective were developed, and
      which had a lower impact on quality of life, there might be up to a 17% increase
      in demand for RRT in those aged over 75 years; around 90% of this increased
      demand would be for haemodialysis.

PMID- 17217543
TI  - The effect of high correlated colour temperature office lighting on employee
      wellbeing and work performance.
AB  - BACKGROUND: The effects of lighting on the human circadian system are well
      established. The recent discovery of 'non-visual' retinal receptors has confirmed
      an anatomical basis for the non-image forming, biological effects of light and
      has stimulated interest in the use of light to enhance wellbeing in the corporate
      setting. METHODS: A prospective controlled intervention study was conducted
      within a shift-working call centre to investigate the effect of newly developed
      fluorescent light sources with a high correlated colour temperature (17000 K)
      upon the wellbeing, functioning and work performance of employees. Five items of
      the SF-36 questionnaire and a modification of the Columbia Jet Lag scale, were
      used to evaluate employees on two different floors of the call centre between
      February and May 2005. Questionnaire completion occurred at baseline and after a
      three month intervention period, during which time one floor was exposed to new
      high correlated colour temperature lighting and the other remained exposed to
      usual office lighting. Two sided t-tests with Bonferroni correction for type I
      errors were used to compare the characteristics of the two groups at baseline and
      to evaluate changes in the intervention and control groups over the period of the
      study. RESULTS: Individuals in the intervention arm of the study showed a
      significant improvement in self-reported ability to concentrate at study end as
      compared to those within the control arm (p < 0.05). The mean individual score on
      a 5 point Likert scale improved by 36.8% in the intervention group, compared with
      only 1.7% in the control group. The majority of this improvement occurred within
      the first 7 weeks of the 14 week study. Substantial within group improvements
      were observed in the intervention group in the areas of fatigue (26.9%),
      alertness (28.2%), daytime sleepiness (31%) and work performance (19.4%), as
      assessed by the modified Columbia Scale, and in the areas of vitality (28.4%) and
      mental health (13.9%), as assessed by the SF-36 over the study period.
      CONCLUSION: High correlated colour temperature fluorescent lights could provide a
      useful intervention to improve wellbeing and productivity in the corporate
      setting, although further work is necessary in quantifying the magnitude of
      likely benefits.

PMID- 17217544
TI  - An association study of DRD2 and COMT polymorphisms with novelty seeking and harm
      avoidance scores, in two independent samples of depressed patients.
AB  - BACKGROUND: It was recently reported that an interaction of the dopamine D2
      receptor (DRD2) and catechol-O-methyltransferase (COMT) influences the
      behavioural approach system--as measured using Carver and White's Behavioural
      Inhibition and Behavioural Approach System (BIS/BAS) scales--in a sample of
      healthy German subjects. The Temperament and Character Inventory (TCI), in
      particular the novelty seeking (NS) and harm avoidance (HA) scales, correlates
      moderately with the BIS/BAS measure. This study aimed to examine support for an
      association of DRD2 and COMT with behavioural activation, using the TCI within
      two independent samples of depressed outpatients (for both samples n = 146).
      METHODS: Two clinical samples of depressed patients were ascertained to assess
      the efficacy of two different pharmacotherapy and psychotherapy treatments.
      Analysis of variance (ANOVA) was used to analyse NS and HA scale and subscale
      scores with respect to gene loci within each clinical sample. Analysis of
      covariance were undertaken to examine the association of age and gender with NS
      and HA scores. An association of age group or gender with gene loci were explored
      using chi-squared tests, in each sample. RESULTS: No significant effect of DRD2
      or COMT, either independently or as an interaction, on NS or HA scores was
      observed, within either sample. Whilst age was significantly negatively
      associated with NS scores, including age in the two- and three-way interactions
      did not affect the significance of the association of personality with gene loci.
      CONCLUSION: This study suggests that the COMT-DRD2 Equilibrium Model of Positive
      Emotionality recently proposed by Reuter and his colleagues is not applicable
      amongst currently depressed individuals, whose behavioural approach and
      inhibition tendencies have been assessed using the TCI.

PMID- 17217545
TI  - Development, feasibility and performance of a health risk appraisal questionnaire
      for older persons.
AB  - BACKGROUND: Health risk appraisal is a promising method for health promotion and
      prevention in older persons. The Health Risk Appraisal for the Elderly (HRA-E)
      developed in the U.S. has unique features but has not been tested outside the
      United States. METHODS: Based on the original HRA-E, we developed a
      scientifically updated and regionally adapted multilingual Health Risk Appraisal
      for Older Persons (HRA-O) instrument consisting of a self-administered
      questionnaire and software-generated feed-back reports. We evaluated the
      practicability and performance of the questionnaire in non-disabled community
      dwelling older persons in London (U.K.) (N = 1090), Hamburg (Germany) (N = 804),
      and Solothurn (Switzerland) (N = 748) in a sub-sample of an international
      randomised controlled study. RESULTS: Over eighty percent of invited older
      persons returned the self-administered HRA-O questionnaire. Fair or poor self
      perceived health status and older age were correlated with higher rates of non
      return of the questionnaire. Older participants and those with lower educational
      levels reported more difficulty in completing the HRA-O questionnaire as compared
      to younger and higher educated persons. However, even among older participants
      and those with low educational level, more than 80% rated the questionnaire as
      easy to complete. Prevalence rates of risks for functional decline or problems
      were between 2% and 91% for the 19 HRA-O domains. Participants' intention to
      change health behaviour suggested that for some risk factors participants were in
      a pre-contemplation phase, having no short- or medium-term plans for change. Many
      participants perceived their health behaviour or preventative care uptake as
      optimal, despite indications of deficits according to the HRA-O based evaluation.
      CONCLUSION: The HRA-O questionnaire was highly accepted by a broad range of
      community-dwelling non-disabled persons. It identified a high number of risks and
      problems, and provided information on participants' intention to change health
      behaviour.

PMID- 17217546
TI  - The PRO-AGE study: an international randomised controlled study of health risk
      appraisal for older persons based in general practice.
AB  - BACKGROUND: This paper describes the study protocol, the recruitment, and base
      line data for evaluating the success of randomisation of the PRO-AGE (PRevention
      in Older people-Assessment in GEneralists' practices) project. METHODS/DESIGN: A
      group of general practitioners (GPs) in London (U.K.), Hamburg (Germany) and
      Solothurn (Switzerland) were trained in risk identification, health promotion,
      and prevention in older people. Their non-disabled older patients were invited to
      participate in a randomised controlled study. Participants allocated to the
      intervention group were offered the Health Risk Appraisal for Older Persons (HRA
      O) instrument with a site-specific method for reinforcement (London: physician
      reminders in electronic medical record; Hamburg: one group session or two
      preventive home visits; Solothurn: six-monthly preventive home visits over a two
      year period). Participants allocated to the control group received usual care. At
      each site, an additional group of GPs did not receive the training, and their
      eligible patients were invited to participate in a concurrent comparison group.
      Primary outcomes are self-reported health behaviour and preventative care use at
      one-year follow-up. In Solothurn, an additional follow-up was conducted at two
      years. The number of older persons agreeing to participate (% of eligible
      persons) in the randomised controlled study was 2503 (66.0%) in London, 2580
      (53.6%) in Hamburg, and 2284 (67.5%) in Solothurn. Base-line findings confirm
      that randomisation of participants was successful, with comparable
      characteristics between intervention and control groups. The number of persons (%
      of eligible) enrolled in the concurrent comparison group was 636 (48.8%) in
      London, 746 (35.7%) in Hamburg, and 1171 (63.0%) in Solothurn. DISCUSSION: PRO
      AGE is the first large-scale randomised controlled trial of health risk appraisal
      for older people in Europe. Its results will inform about the effects of
      implementing HRA-O with different methods of reinforcement.

PMID- 17217547
TI  - UK waiting time targets in lung cancer treatment: are they achievable? Results of
      a prospective tracking study.
AB  - BACKGROUND: Recent guidelines have specified a number of waiting time targets to
      prevent delay in the treatment of lung cancer. This study was carried out to
      assess the quality of lung cancer services and compare with national
      recommendations. METHODS: All newly diagnosed cases of lung cancer presenting to
      our institution via general practitioner referral were entered into a prospective
      tracking study by a dedicated audit officer. From September 2003 to March 2005 a
      total of 247 patients were entered into the study. Of these 133 (54%) were
      referred by general practitioners and the remainder 114 (46%) were internal
      referrals. The Cancer Plan waiting time targets are mainly applicable to GP
      referrals, which formed the study group. RESULTS: All the patients were seen in
      chest out-patients clinic within the recommended two weeks period. However there
      was a delay in starting all forms of treatment. The median waiting time to any
      form of treatment was 60 days (recommendation 62 days for all patients).
      CONCLUSION: This data demonstrates that although patients receive out patient
      consultation in the recommended time period, the National Cancer Plan 62 days GP
      referral to treatment target is not being achieved. A concerted effort by all
      clinicians is required to meet the prescribed target times.

PMID- 17217548
TI  - HIV epidemic trend and antiretroviral treatment need in Karonga District, Malawi.
AB  - We describe the development of the HIV epidemic in Karonga District, Malawi over
      22 years using data from population surveys and community samples. These data are
      used to estimate the trend in HIV prevalence, incidence and need for
      antiretroviral treatment (ART) using a simple mathematical model. HIV prevalence
      rose quickly in the late 1980s and early 1990s, stabilizing at around 12% in the
      mid-1990s. Estimated annual HIV incidence rose quickly, peaking in the early
      1990s at 2.2% among males and 3.1% among females, and then levelled off at 1.3%
      among males and 1.1% among females by the late 1990s. Assuming a 2-year
      eligibility period, both our model and the UNAIDS models predicted 2.1% of adults
      were in need of ART in 2005. This prediction was sensitive to the assumed
      eligibility period, ranging from 1.6% to 2.6% if the eligibility period was
      instead assumed to be 1.5 or 2.5 years, respectively.

PMID- 17217549
TI  - HIV-1 and HIV-2 prevalence and associated risk factors among postnatal women in
      Harare, Zimbabwe.
AB  - Studies of antenatal women form the predominant source of data on HIV-1
      prevalence in Africa. Identifying factors associated with prevalent HIV is
      important in targeting diagnostic services and care. Between November 1997 and
      January 2000, 14,110 postnatal women from Harare, Zimbabwe were tested by ELISAs
      reactive to both HIV-1 and HIV-2; a subset of positive samples was confirmed with
      assays specific for HIV-1 and HIV-2. Baseline characteristics were elicited and
      modelled to identify risk factors for prevalent HIV infection. HIV-1 and HIV-2
      prevalences were 32.0% (95% CI 31.2-32.8) and 1.3% (95% CI 1.1-1.5),
      respectively; 4% of HIV-1-positive and 99% of HIV-2-positive women were co
      infected. HIV-1 prevalence increased from 0% among 14-year-olds to >45% among
      women aged 29-31 years, then fell to <20% among those aged>40 years. In
      multivariate analyses, prevalence increased with parity, was lower in married
      women than in single women, divorcees and widows, and higher in women with the
      lowest incomes and those professing no religion. Adjusted HIV-1 prevalence
      increased during 1998 and decreased during 1999. Age modified the effects of
      parity, home ownership and parental education. Among older women, prevalence was
      greater for women who were not homeowners. Among younger women, prevalence
      increased with parity and low parental education. None of these factors
      distinguished women co-infected with HIV-2 from those infected with HIV-1 alone.
      Prevalent HIV-1 infection is associated with financial insecurity and weak
      psychosocial support. The ZVITAMBO study apparently spanned the peak of the HIV-1
      epidemic among reproductive women in Harare.

PMID- 17217550
TI  - Detection of antibodies to Japanese encephalitis virus in the wild boars in
      Hiroshima prefecture, Japan.
AB  - Serum specimens were collected from 25 wild boars in Hiroshima prefecture located
      in the western region of Japan from November 2004 to February 2005. The sera were
      tested for antibodies to Japanese encephalitis virus (JEV) by IgM capture and IgG
      enzyme-linked immunosorbent assays (ELISA), and plaque reduction neutralization
      test. Seventeen samples (68%) were positive for neutralizing antibody to JEV. All
      the neutralizing antibody-positive samples were positive for IgG-ELISA. One was
      also positive for IgM. The results indicate that approximately 70% of the wild
      boars were positive for anti-JEV antibody, and raises the possibility that wild
      boars may play a role in the infectious cycle of JEV in this region.

PMID- 17217551
TI  - Optimizing typhoid fever case definitions by combining serological tests in a
      large population study in Hechi City, China.
AB  - Blood culture-based diagnosis can only detect a fraction of the total burden of
      Salmonella enterica subsp. enterica serovar Typhi. The objective of the study was
      to detect additional typhoid fever cases through serological tests. A total of
      1732 prolonged fever episodes were evaluated using three serological tests,
      Widal, Tubex and Typhidot-M in a typhoid fever endemic area of southern China. A
      case definition which included a positive Widal test (TO>or=80 & TH>A), a
      positive Tubex test (>or=4) and a positive Typhidot-M test, increased the
      detection of cases by more than twofold from 13 to 28 cases. The case definition
      has a specificity of 100% and a sensitivity of 39%. Case definitions based on
      combinations of serological tests can detect additional typhoid fever cases with
      higher specificity than a single serological test. Improved case detection is
      essential to understand the true disease burden and can help to boost the power
      of intervention trials.

PMID- 17217552
TI  - Duration and distance of exposure are important predictors of transmission among
      community contacts of Ontario SARS cases.
AB  - We report attack rates and contact-related predictors among community contacts of
      severe acute respiratory syndrome (SARS) cases from the 2003 Toronto-area
      outbreak. Community contact data was extracted from public health records for
      single, well-defined exposures to a SARS case. In total, 8662 community-acquired
      exposures resulted in 61 probable cases; a crude attack rate of 0.70% [95%
      confidence interval (CI) 0.54-0.90]. Persons aged 55-69 years were at higher risk
      of acquiring SARS (1.14%) than those either younger (0.60%) or older (0.70%). In
      multivariable analysis exposures for at least 30 min at a distance of <or=1 m
      increased the likelihood of becoming a SARS case 20.4-fold (95% CI 11.8-35.1).
      Risk related to duration of illness in the source case at time of exposure was
      greatest for illness duration of 7-10 days (rate ratio 3.4, 95% CI 1.9-6.1).
      Longer and closer proximity exposures incurred the highest rate of disease.
      Separate measures of time and distance from source cases should be added to
      minimum datasets for the assessment of interventions for SARS and other emerging
      diseases.

PMID- 17217553
TI  - Soya protein during pregnancy--an opportunity to attenuate the progression of
      chronic kidney disease?

PMID- 17217554
TI  - Dietary supplementation with an extract of lycopene-rich tomatoes does not reduce
      atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits.
AB  - Tomatoes are rich in lycopene and other carotenoids which have shown beneficial
      effects on CVD in epidemiological and intervention studies. In the present study
      the effect of an extract of lycopene-rich tomatoes, Lyc-O-Mato on atherosclerosis
      was studies in Watanabe Heritable Hyperlipidemic rabbits. The rabbits were fed a
      control diet, a control diet supplemented with the tomato extract or a control
      diet supplemented with a mixture of plant oils for 16 weeks. Lycopene was
      detected only in plasma of rabbits receiving tomato extract. The tomato extract
      had no effect on cholesterol and triacylglycerol levels measured in total plasma,
      lipoprotein fractions and on aortic atherosclerosis evaluated biochemically and
      by microscopy. Oxidation of lipids in unfractionated plasma also was unaffected
      by the intake of tomato extract. In conclusion, the tomato extract increased
      plasma levels of lycopene in rabbits, but had no effect on hypercholesterolaemia,
      oxidation of plasma lipids or aortic atherosclerosis.

PMID- 17217555
TI  - The lipoprotein/lipid profile is modulated by a gene-diet interaction effect
      between polymorphisms in the liver X receptor-alpha and dietary cholesterol
      intake in French-Canadians.
AB  - Genetic and nutritional factors interact together and modulate the plasma lipid
      profile. We identified variations in the gene encoding the liver X receptor alpha
      (LXRalpha) and investigated their effects on the plasma lipoprotein/lipid
      profile. We also examined whether the association between cholesterol intake and
      plasma lipid profile was modulated by LXRalpha variants. The LXRalpha gene was
      sequenced in thirty-five French-Canadian men with high plasma total cholesterol
      (>5.0 mmol/l) and LDL-cholesterol (>3.5 mmol/l) concentrations. dietary
      cholesterol was obtained from a food-frequency questionnaire. The LXRalpha c.
      115G>A, c.-840C>A and c.-1830T>C genotypes were determined by direct sequencing
      in 732 subjects. Molecular screening of the LXRalpha gene revealed sixteen
      variants. Genotypes c.-115G>A, c.-840C>A and c.-1830T>C (rare allele frequency of
      14.3%, 14.2% and 11.0%, respectively) were analysed further. Plasma total
      cholesterol concentrations were higher in carriers of the -115A, -840A and -1830C
      allele, compared with the -115G/G, -840C/C and -1830T/T homozygotes (P< or
      =0.05). In a model including the c.-115G>A polymorphism, cholesterol intake, the
      interaction term c.-115G>A x cholesterol intake (mg/d) and covariates, LXRalpha
      115G>A explained 1.8% and 2.1% of the variance in total cholesterol and LDL
      cholesterol concentrations (P=0.02 and P=0.01), whereas the interaction term
      explained 2.9% (P=0.002) and 2.8% (P=0.005), respectively. When subjects were
      divided into four groups according to the median of cholesterol (290.8 mg) and 
      115G>A genotypes, high cholesterol intake was associated with higher cholesterol
      levels in -115A carriers. Similar results were observed for c.-840C>A and c.
      1830T>C. These results suggest that cholesterol intake interacts with LXRalpha
      variants to modulate the plasma lipid profile.

PMID- 17217556
TI  - Dose-dependent modulation of the T cell proteome by ascorbic acid.
AB  - To investigate the hypothesis that the micronutrient ascorbic acid can modulate
      the functional genome, T cells (CCRF-HSB2) were treated with ascorbic acid (up to
      150 microM) for up to 24 h. Protein expression changes were assessed by two
      dimensional electrophoresis. Forty-one protein spots which showed greater than
      two-fold expression changes were subject to identification by matrix-assisted
      laser desorption ionisation time of flight MS. The confirmed protein
      identifications were clustered into five groups; proteins were associated with
      signalling, carbohydrate metabolism, apoptosis, transcription and immune
      function. The increased expression of phosphatidylinositol transfer protein
      (promotes intracellular signalling) within 5 min of ascorbic acid treatment was
      confirmed by Western blotting. Together, these observations suggest that ascorbic
      acid modulates the T cell proteome in a time- and dose-dependent manner and
      identify molecular targets for study following antioxidant supplementation in
      vivo.

PMID- 17217557
TI  - Serum leptin and insulin levels in lactating protein-restricted rats:
      implications for energy balance.
AB  - The present study analysed the effect of protein restriction on serum insulin and
      leptin levels and their relationship with energy balance during lactation. Four
      groups of rats received isocaloric diets containing 170 g protein/kg or 60 g
      protein/kg from pregnancy until the 14th day of lactation: control non-lactating,
      control lactating (both fed a control diet), low-protein non-lactating and low
      protein lactating. Energy intake, body composition, energy balance, serum insulin
      and leptin concentrations and the relationship between these hormones and several
      factors related to obesity were analysed. Low-protein-intake lactating rats
      exhibited hypoinsulinaemia, hyperleptinaemia, hypophagia and decreased energy
      expenditure compared with control lactating rats. The protein level in the
      carcasses was lower in the low-protein lactating group than in the control
      lactating group, resulting in a higher fat content in the first group compared
      with the latter. Body fat correlated inversely with serum insulin and positively
      with serum leptin level. There was a significant negative correlation between
      serum leptin and energy intake, and a positive relationship between energy intake
      and serum insulin level in lactating rats and in the combined data from both
      groups. Energy expenditure was correlated positively with serum insulin and
      negatively with serum leptin in lactating rats and when data from control non
      lactating and lactating rats were pooled. Lactating rats submitted to protein
      restriction, compared with lactating control rats, showed that maternal reserves
      were preserved owing to less severe negative energy balance. This metabolic
      adaptation was obtained, at least in part, by hypoinsulinaemia that resulted in
      increased insulin sensitivity favouring enhanced fat deposition, hyperleptinaemia
      and hypophagia.

PMID- 17217558
TI  - Deposition of dietary fatty acids, de novo synthesis and anatomical partitioning
      of fatty acids in finishing pigs.
AB  - Predicting aspects of pork quality becomes increasingly important from both a
      nutritional and technological point of view. The aim of the present study was to
      provide quantitative information on the relation between nutrient intake and
      whole-body fatty acid (FA) depositions. This information is essential to develop
      mechanistic models predicting the FA content of tissues. A serial slaughter study
      was carried out in which thirty pigs were slaughtered between 90 and 150 kg. The
      diet included 15 g/kg soyabean oil and contained 44 g/kg fat. Only 0.31 and 0.40
      of the digested n-6 and n-3 FA were deposited, respectively. Approximately one
      third of the n-3 supply that was deposited resulted from the conversion of 18:3
      to other metabolites (i.e. EPA, docosapentaenoic acid and DHA). This proportion
      was affected by the pig genotype. De novo-synthesised FA represented 0.86 of the
      total non-essential FA deposition, and its average composition corresponded to
      0.017, 0.286, 0.025, 0.217 and 0.454 for 14:0, 16:0, 16:1, 18:0 and 18:1,
      respectively. Although the average whole-body FA composition was relatively
      constant during the finishing period, this was not so for the tissues. In the
      carcass (without backfat), the content of 18:1 increased during the finishing
      period, whereas that of 16:0 and 18:0 decreased. Backfat captured a
      proportionally greater fraction of 18:2 than did the carcass of the residual
      tissues. In contrast, a proportionally greater fraction of the dietary 18:3
      supply was deposited in the carcass compared to other tissues.

PMID- 17217559
TI  - Main intestinal markers associated with the changes in gut architecture and
      function in piglets after weaning.
AB  - We analysed the spatio-temporal sequence of events concerning the morphology,
      physiology and ecology of the gut of piglets during the 2 weeks following
      weaning, in order to provide a limited number of variables that could be relevant
      markers of the gut post-weaning changes. An experiment was conducted on sixty
      piglets fasted for 2 d, then administered a weaning diet with a moderate or a
      high content of wheat using controlled gastric feeding, and slaughtered at
      different time-points post-weaning. Sixty-nine variables were analysed by
      principal component analysis. The results showed that the temporal changes
      induced in the gut by weaning can be divided into two periods: an acute period
      happening immediately after weaning, followed after day 5 by a more progressive
      adaptative and maturational phase. The main factors of this adaptation were the
      refeeding process and the time, while the diet per se had little influence. The
      villus length, lactose activity, macromolecule fluxes across the jejunum and the
      plasma cholecystokinin were proposed as markers of the acute phase. Ths mass of
      the jejunum, the weight of the pancrease, the content of stomach, the trypsin
      activity and the theophyl-line-induced secretion in jejunum were related to the
      re-feeding. Markers proposed to follow the gut maturation were the maltase
      activity, the glucose absorption and the basal resistance in the ileum, the
      lactobacilli and enterococci in the colon, and the pH of colonic and caecal
      contents. These markers might be helpful to design suitable diets to limit posts
      weaning gut disorders in pigs.

PMID- 17217560
TI  - Dietary trans 10, cis 12-conjugated linoleic acid reduces the expression of fatty
      acid oxidation and drug detoxification enzymes in mouse liver.
AB  - Mice fed diets containing trans 10, cis 12 (t10, c12)-conjugated linoleic acid
      (CLA) develop fatty livers and the role of the hepatic fatty acid oxidation
      enzymes in this development is not well defined. We examined the effects of
      dietary cis 9, trans 11-CLA (c9, t11-CLA) and t10, c12-CLA on the expression of
      hepatic genes for fatty acid metabolism. Female mice, 8 weeks old, (six animals
      per group) were fed either a control diet or diets supplemented with 0.5% c9, t11
      or c12-CLA for 8 weeks. DNA microarray analysis showed that t10, c12-CLA
      increased the expression of 278 hepatic genes and decreased those of 121 genes
      (>2 fold); c9, t11-CLA increased expression of twenty-two genes and decreased
      those of nine. Real-time PCR confirmed that t10, c12-CLA reduced by the
      expression of fatty acid oxidation genes including flavin monooxygenase (FMO)-3
      95%, cytochrome P450 (cyt p450) 69%, carnitine palmitoyl transferase 1a 77%,
      acetyl CoA oxidase (ACOX) 50% and PPARalpha 65%: it increased the expression of
      fatty acid synthase by 3.5-fold (P<0.05 for all genes, except ACOX P=0.08). It
      also reduced the enzymatic activity of hepatic microsomal FMO by 40% and the FMO3
      specific protein by 67%. c9, t11-CLA reduced FMO3 and cyt P450 expression by 61%
      (P=0.001) and 38% (P=0.06) and increased steoryl CoA desaturase transcription by
      5.9-fold (P=0.07). Both decreased fatty acid oxidation and increased fatty acid
      synthesis seem to contribute to the CLA-induced fatty liver. Since FMO and cyt
      P450 are also involved in drug detoxification, suppression of the transcription
      of these genes by CLA may have other health consequences besides development of
      fatty liver.

PMID- 17217561
TI  - The Driselase-treated fraction of rice bran is a more effective dietary factor to
      improve hypertension, glucose and lipid metabolism in stroke-prone spontaneously
      hypertensive rats compared to ferulic acid.
AB  - The aim of this study is to investigate the effects of dietary supplementation
      with the Driselase-treated fraction (DF) of rice bran and ferulic acid (FA) on
      hypertension and glucose and lipid metabolism in stroke-prone spontaneously
      hypertensive rats (SHRSP). Male SHRSP at 4 weeks of age were divided into three
      groups, and for 8 weeks were fed (1) a control diet based on AIN-93M, (2) a DF of
      rice bran-supplemented diet at 60 g/kg and (3) an FA-supplemented diet at 0.01
      g/kg. Means and standard errors were calculated and the data were tested by one
      way ANOVA followed by a least significance difference test. The results showed
      that both the DF and FA diets significantly improved hypertension as well as
      glucose tolerance, plasma nitric oxide (NOx), urinary 8-hydroxy-2'-deoxyguanosine
      and other parameters. In particular, compared to the FA diet, the DF diet
      produced a significant improvement in urinary NOx, hepatic triacylglycerol and
      several mRNA expressions of metabolic parameters involved in glucose and lipid
      metabolisms. The results of the metabolic syndrome-related parameters obtained
      from this study suggest that the DF diet is more effective than the FA diet.

PMID- 17217562
TI  - Dietary soya protein during pregnancy and lactation in rats with hereditary
      kidney disease attenuates disease progression in offspring.
AB  - Dietary soya protein substitution for casein initiated at weaning slows disease
      progression in animal models of chronic renal disease. As there is increasing
      evidence that fetal programming can have a significant impact on kidney
      physiology and function in offspring, the objective of the current study was to
      determine whether exposure to soya protein in the diet earlier than weaning would
      have further benefits. Han:SPRD-cy (cy/+) breeder rats were fed a casein-based or
      soya protein-based diet 2 weeks prior to mating, throughout pregnancy and during
      lactation. Following this maternal period, 3-week-old pups were given either the
      same or the alternate diet for a 7-week weaning period. Dietary soya protein
      compared with casein in the maternal or weaning period both independently
      resulted in less renal inflammation (macrophage infiltration lower by 24%
      (P=0.0003) and 32% (P<0.001), respectively). When soya protein was given in both
      feeding periods, the effect was additive. Soya protein substitution for casein
      resulted in less oxidative damages as indicated by 28% lower oxidized-LDL
      staining (P=0.013) when present in the maternal period, or in the weaning period
      (by 56%, P<0.0001). Renal cell proliferation was reduced by 29-33% (P<0.05) in
      rats given soya protein whether the exposure was during the maternal or weaning
      period. Soya protein compared with casein in the maternal period also resulted in
      33% (P=0.0013) less proteinuria, indicating superior renal function. Dietary soya
      protein during pregnancy and lactation represents a potential preventative
      approach in treating for those with congenital kidney diseases.

PMID- 17217563
TI  - Comparative analysis of sesame lignans (sesamin and sesamolin) in affecting
      hepatic fatty acid metabolism in rats.
AB  - Effects of sesamin and sesamolin (sesame lignans) on hepatic fatty acid
      metabolism were compared in rats. Rats were fed either a lignan-free diet, a diet
      containing 0.6 or 2 g/kg lignan (sesamin or sesamolin), or a diet containing both
      sesamin (1.4 g/kg) and sesamolin (0.6 g/kg) for 10 d. Sesamin and sesamolin dose
      dependently increased the activity and mRNA abundance of various enzymes involved
      in hepatic fatty acid oxidation. The increase was much greater with sesamolin
      than with sesamin. These lignans increased parameters of hepatic fatty acid
      oxidation in an additive manner when added simultaneously to an experimental
      diet. In contrast, they decreased the activity and mRNA abundance of hepatic
      lipogenic enzymes despite dose-dependent effects not being necessarily obvious.
      Sesamin and sesamolin were equally effective in lowering parameters of
      lipogenesis. Sesamolin accumulated in serum at 33- and 46-fold the level of
      sesamin at dietary concentrations of 0.6 and 2 g/kg, respectively. The amount of
      sesamolin accumulated in liver was 10- and 7-fold that of sesamin at the
      respective dietary levels. Sesamolin rather than sesamin can account for the
      potent physiological effect of sesame seeds in increasing hepatic fatty acid
      oxidation observed previously. Differences in bioavailability may contribute to
      the divergent effects of sesamin and sesamolin on hepatic fatty acid oxidation.
      Sesamin compared to sesamolin was more effective in reducing serum and liver
      lipid levels despite sesamolin more strongly increasing hepatic fatty acid
      oxidation.

PMID- 17217564
TI  - A comparative study of the preventative effects exerted by two probiotics,
      Lactobacillus reuteri and Lactobacillus fermentum, in the trinitrobenzenesulfonic
      acid model of rat colitis.
AB  - The intestinal anti-inflammatory effects of two probiotics isolated from breast
      milk, Lactobacillus reuteri and L. fermentum, were evaluated and compared in the
      trinitrobenzenesulfonic acid (TNBS) model of rat colitis. Colitis was induced in
      rats by intracolonic administration of 10 mg TNBS dissolved in 50% ethanol (0.25
      ml). Either L. reuteri or L. fermentum was daily administered orally (5 x 10(8)
      colony-forming units suspended in 0.5 ml skimmed milk) to each group of rats (n
      10) for 3 weeks, starting 2 weeks before colitis induction. Colonic damage was
      evaluated histologically and biochemically, and the colonic luminal contents were
      used for bacterial studies and for SCFA production. Both probiotics showed
      intestinal anti-inflammatory effects in this model of experimental colitis, as
      evidenced histologically and by a significant reduction of colonic
      myeloperoxidase activity (P<0.05). L. fermentum significantly counteracted the
      colonic glutathione depletion induced by the inflammatory process. In addition,
      both probiotics lowered colonic TNFalpha levels (P<0.01) and inducible NO
      synthase expression when compared with non-treated rats; however, the decrease in
      colonic cyclo-oxygenase-2 expression was only achieved with L.fermentum
      administration. Finally, the two probiotics induced the growth of Lactobacilli
      species in comparison with control colitic rats, but the production of SCFA in
      colonic contents was only increased when L. fermentum was given. In conclusion,
      L. fermentum can exert beneficial immunomodulatory properties in inflammatory
      bowel disease, being more effective than L. reuteri, a probiotic with reputed
      efficacy in promoting beneficial effects on human health.

PMID- 17217565
TI  - The effects of changes in nutritional demand on gastrointestinal parasitism in
      lactating rats.
AB  - Lactating rats experience a breakdown of immunity to parasites, i.e. they carry
      larger worm burdens after re-infection compared to their non-lactating
      counterparts. Feeding high-protein foods to lactating rats results in reduced
      worm burdens. This could be attributed to changes in gastrointestinal environment
      or to overcoming effects of nutrient scarcity on host immunity. The latter
      hypothesis was addressed through a manipulation of nutrient demand by
      manipulating litter size. Twenty-three rats were immunized prior to mating and re
      infected on day 2 of lactation with 1600 infective Nippostrongylus brasiliensis
      larvae. From parturition onwards, rats received ad libitum low-protein food (100
      g crude protein/kg). Litter size were standardised to nine (LS9), six (LS6) or
      three (LS3) pups, by day 2 of lactation. After a further 10 d, LS9 and LS6 rats
      carried more worms than LS3 rats. However, feeding treatment did not affect
      concentrations of mucosal inflammatory cells. Achieved feed intake did not differ
      consistently between the treatment groups. However, LS9 and LS6 rats lost weight,
      whilst LS3 rats gained weight during lactation. The results support the view that
      resistance to N. brasiliensis is sensitive to changes in nutrient demand, and the
      improved resistance to N. brasiliensis is likely due to effects of overcoming
      nutrient scarcity on host immunity.

PMID- 17217566
TI  - Short duration of breast-feeding as a risk-factor for beta-cell autoantibodies in
      5-year-old children from the general population.
AB  - Breast-feeding has been suggested to have a protective effect against the
      development of type 1 diabetes. In the present study, we investigated the
      relation between duration of breast-feeding and beta-cell autoantibodies in 5
      year-old non-diabetic children who participated in a prospective population-based
      follow-up study (the All Babies in Southeast Sweden study). Autoantibodies to
      insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tryosine
      phosphatase-like IA-2 (IA-2A) were measured by radiobinding assays. A short
      duration of total breast-feeding was associated with an increased risk of GADA
      and/or IAA above the ninety-fifth percentile at 5 years of age (OR 2.09, 95% CI
      1.45, 3.02; P<0.000) as well as with an increased risk of IAA above the ninety
      fifth percentile at this age (OR 2.89, 95% CI 1.81, 4.62, P<0.000). A short
      duration of exclusive breast-feeding was associated with an increased risk of
      GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 2.01, 95% CI 1.08,
      3.73; P=0.028) as well as with an increased risk of IA-2A above the ninety-ninth
      percentile (OR 3.50, 95% CI 1.38, 8.92, P=0.009) at 5 years of age. An early
      introduction of formula was associated with an increased risk of GADA, IAA and/or
      IA-2A above the ninety-ninth percentile (OR 1.84, 95% CI 1.01, 3.37; P=0.047) at
      5 years of age. The positive association between a short duration of both total
      and exclusive breast-feeding, as well as an early introduction of formula, and
      positivity for beta-cell autoantibodies in children from the general population
      suggest that breast-feeding modifies the risk of beta-cell autoimmunity, even
      years after finishing breast-feeding.

PMID- 17217567
TI  - Trans-10, cis-12-conjugated linoleic acid increases phagocytosis of porcine
      peripheral blood polymorphonuclear cells in vitro.
AB  - Trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) has been shown to alter
      immune function. PPARgamma has been shown to potentially play an important role
      in regulating inflammatory and immune responses by modulating the activity of
      monocytes and macrophages. Previous studies have indicated that the phagocytic
      capacity of porcine peripheral blood polymorphonuclear cells (PMN) was enhanced
      by the culture supernatant fraction from t10c12-CL-stimulated porcine peripheral
      blood mononuclear cells (PBMC) but not by t10c12-CLA itself. In the present
      study, we examined the effects of t10c12-CLA on PPARgamma and TNF-alpha
      expression of porcine PBMC and the phagocytic capacity of PMN. t10c12-CLA
      increased TNF-alpha mRNA expression and production by PBMC. The phagocytic
      capacity of porcine PMN was enhanced by either culture supernatant fraction from
      PBMC treated with t10c12-CLA or recombinant porcine (rp) TNF-alpha. Anti-rpTNF
      alpha polyclonal antibody inhibited the enhancement of PMN phagocytic capacity.
      t10c12-CLA also up regulated PPARgamma mRNA expression in porcine PBMC. Bisphenol
      A diglycidyl ether, a PPARgamma antagonist, not only completely negated the
      t10c12-CLA-stimulating effects on TNF-alpha expression and production by porcine
      PBMC, but also decreased the enhancement of PMN phagocytic capacity by the t10c12
      CLA-stimulated porcine PBMC culture supernatant fraction. These results suggest
      that t10c12-CLA has an immunostimulating effect on porcine PMN phagocytic
      capacity, which is mediated by TNF-alpha from PBMC via a PPARgamma-dependent
      pathway.

PMID- 17217568
TI  - Composition and metabolism of the intestinal microbiota in consumers and non
      consumers of yogurt.
AB  - The objective of the present study was to evaluate the impact of a regular
      consumption of yogurt on the composition and metabolism of the human intestinal
      microbiota. Adult subjects were selected on the basis of daily food records and
      divided into two groups: yogurt consumers (at least 200 g yogurt consumed per d,
      n 30); non-consumers (no yogurt, n 21). Their faecal microbiota was analysed
      using molecular methods (in situ hybridisation and PCR amplification combined
      with separation by denaturing gel electrophoresis) and its metabolic
      characteristics were assessed by measuring glycosidase, P-glucuronidase and
      reductase activities and profiling SCFA, neutral sterols and bile acids. The
      yogurt starter Lactobacillus delbrueckii ssp. bulgaricus (identity confirmed by
      16S rRNA sequencing) was detected in 73% of faecal samples from fermented milk
      consumers v. 28% from non-consumers (P=0.003). In yogurt consumers, the level of
      Enterobacteriaceae was significantly lower (P=0.006) and 13-galactosidase
      activity was significantly increased (P=0.048). In addition, within this group, 3
      galactosidase activity and the Bifidobacterium population were both positively
      correlated with the amount of fermented milk ingested (r 0.66, P<0.0001 and r
      0.43, P=0.018, respectively). Apart from these effects, which can be considered
      beneficial to the host, no other major differences could be detected regarding
      the composition and metabolic activity of intestinal microbiota.

PMID- 17217569
TI  - Two high-amylose maize starches with different amounts of resistant starch vary
      in their effects on fermentation, tissue and digesta mass accretion, and
      bacterial populations in the large bowel of pigs.
AB  - Four groups of young pigs (n 6) were fed a diet containing 50% maize starch as
      either a highly digestible waxy starch (control; 0% amylose) or one of three
      resistant starch (RS) diets, namely a high-amylose maize starch (HAMS; 85%
      amylose), this starch subjected to hydrothermal treatment (HTHAMS; 85% amylose),
      or a blend of HAMS and HTHAMS included in equal amounts, for 21 d. Food intake
      and live weight at the end of the study were similar among the four groups. Ileal
      starch digestibility was lower in pigs fed the three RS diets but was greater for
      HAMS(88%) than for HTHAMS (70%; P<0.05). Faecal output and large bowel digesta
      mass, and concentrations and pools of individual and total SCFA were higher (by
      about two- to threefold; all P<0.05) and digesta pH lower (by about 1 unit, all
      P<0.001) in pigs fed either HAMS or HTHAMS compared to the controls. These
      differences in biomarkers were seen along the length of the large bowel. Colon
      length was 0.5-0.9 m longer (19-35%) in pigs fed the high-RS diets relative to
      those fed the highly digestible starch diet (P<0.05). Faecal and proximal colonic
      lactobacilli and bifidobacteria numbers were higher (by 1 and 3 log units; P<
      0.05) in pigs fed the HAMS or HTHAMS diets. Although both high-amylose starches
      promoted fermentation throughout the large bowel, the data suggest that the
      effects of HTHAMS may be more pronounced in the distal region compared to those
      of HAMS.

PMID- 17217570
TI  - Inter-household and intra-household patterns of fish and meat consumption in
      fishing communities in two states in Nigeria.
AB  - Fish is generally regarded as a primary source of protein for many poor African
      fishing communities. The present study compared the relative importance of fish
      as a high-quality dietary protein source with meat in fishing communities in two
      states in Nigeria. Fifty fishing households in which active fishing was the
      primary activity and fifty non-fishing households (agriculture being stated as
      primary activity) in traditional fishing communities were randomly selected in
      the coastal state of Lagos and the inland state of Niger. A simple weighing
      balance was designed and given to each household to measure fish or meat entering
      the household for consumption. A comparison of consumption using this method
      against the 24h recall method revealed that the recall method accounted for only
      one third of actual fish consumed. Overall, the price of fish was higher and
      consumption lower in Lagos compared with Niger State. At the household level in
      both states, the consumption of fish in fishing households was twice that of non
      fishing households, whereas meat consumption was similar. A total of thirty-nine
      different fish species were consumed, with Tilapia contributing 24% by weight of
      the fish consumed. In both states, beef was the most frequently consumed meat,
      followed by goat meat. The study revealed a high preference for fresh fish. The
      highest fish consumption occurred in March, corresponding to the period of lowest
      meat consumption. On a unit weight basis, heads of households consumed 59% more
      fish than their wives or children.

PMID- 17217571
TI  - Evaluation of the effectiveness of the national vitamin A supplementation
      programme among school children in Sri Lanka.
AB  - The Ministry of Health in Sri Lanka commenced a vitamin A supplementation
      programme of school children with a megadose of 105 micromol (100,000 IU) vitamin
      A in school years 1, 4 and 7 (approximately 5-, 9- and 12-year-olds,
      respectively) in 2001. We evaluated the vitamin A supplementation programme of
      school children in a rural area of Sri Lanka. A cross-sectional study was
      conducted among children supplemented with an oral megadose of vitamin A (105
      micromol; n 452) and children not supplemented (controls; n 294) in Grades 1-5.
      Children were clinically examined and a sample of blood was taken for serum
      vitamin A concentration estimation by HPLC. Socio-demographic information was
      obtained from children or mothers. Supplemented children had a higher proportion
      of males and stunted children, were younger and lived under poorer conditions as
      compared to controls. There was no difference in the prevalences of eye signs and
      symptoms of vitamin A deficiency in the two groups. Supplemented children had
      higher serum vitamin A concentrations than controls (1.4 (SD 0.49) micromol/l v.
      1.2 (SD 0.52) micromol/l). The serum vitamin A concentrations were 1.6 (SD 0.45),
      1.4 (SD 0.50), 1.3 (SD 0.44) and 1.1 (SD 0.43) micromol/l in children
      supplemented within 1, 1-6, 7-12 and 13-18 months of supplementation,
      respectively. Vitamin A concentrations were significantly greater than controls
      if supplementation was carried out within 6 months after adjustment. The oral
      megadose of 105 micromol vitamin A maintained serum vitamin A concentrations for
      6 months in school children.

PMID- 17217572
TI  - Calcium absorption in postmenopausal Chinese women: a randomized crossover
      intervention study.
AB  - The Ca intake and food sources of Chinese postmenopausal women are quite
      different from those of their Western counterparts. But, little information on Ca
      metabolism is available in Chinese populations. We determined true fractional
      calcium absorption (TFCA), true Ca absorption(= TFCA x Ca intake, Va), urinary Ca
      excretion (Vu,) and the difference between Va and Vu, (Va-u), in response to
      three dietary Ca intake levels. Twenty-one healthy postmenopausal Chinese women
      aged 49-64 years were recruited for this randomized crossover trial from a
      general community, Guangzhou, China. Subjects were randomly assigned to receive
      0, 500 and 1000 mg Ca/d for 5 weeks separated by 2-week washout periods. TFCA
      using Ca stable isotopes, total urinary Ca excretion and Ca intake were
      determined after 4 weeks of adaptation. Mean values for total Ca intake (Vi) of
      the three phases were 391 (SD 197), 880 (SD 130) and 1382 (SD 160) mg/d. On usual
      diet, TFCA, Vu, Va, and Va-u were 0.57 (SD 0.12), 175 (SD 59) mg/d, 216 (SD 98)
      mg/d and 41 (SD 99) mg/d, respectively. With the supplementations of 500 and 1000
      mg Ca/d, TFCAsignificantly decreased to 0.52 (SD 0.12) and 0.43 (SD 0.13)
      (P<0.001); whereas urinary Ca (P=0.003), Va and Va-u increased significantly (P<
      0.001). Using a mixed-effects nonlinear regression model, it was estimated that
      Va-u was approaching a plateau when mean Ca intake reached 1300 mg/d. In
      conclusion, the present findings suggest postmenopausal Chinese women have high
      Ca absorption efficiency and a mean Ca intake of about 1300 mg/d is required to
      maximize the Va-u.

PMID- 17217573
TI  - Does zinc deficiency play a role in stunting among primary school children in NE
      Thailand?
AB  - Stunting in school-age years may result in a decrease in adult size, and thus
      reduced work capacity and adverse reproductive outcomes. We have compared the
      mean intakes of energy, protein and selected growth-limiting nutrients in fifty
      eight stunted children and 172 non-stunted controls drawn from 567 children aged
      6-13 years attending ten rural schools in NE Thailand. Control children were
      selected randomly after stratifying children by age in each school. Dietary data
      were calculated from 24-h recalls using nutrient values from Thai food
      composition data and chemical analysis. Inter-relationships between stunting and
      sociodemographic, anthropometric and biochemical variables were also examined.
      Biochemical variables investigated were serum albumin, zinc, ferritin,
      transferrin receptor and retinol, and iodine in casual urine samples.
      Significantly more males than females were stunted (males, n 38, 65.5% v.
      females, n 20. 34.5%: P=0.025). Stunted males had lower mean intakes of energy,
      protein, calcium, phosphorus and zinc, and a lower mean (95% CI) serum zinc (9.19
      (8.53, 9.84) v. 9.70 (8.53, 9.29) micromol/1) than non-stunted males; no other
      biochemical differences were noted. Stunted males also had a lower mean arm
      muscle area (P= 0.015), after adjusting for age, than non-stunted males. In
      conclusion, the lower dietary intakes of the stunted males compared to their non
      stunted counterparts may be associated with anorexia and hypogeusia induced by
      zinc deficiency. Hence, zinc deficiency may be a factor limiting linear growth,
      especially among boys in NE Thailand, but more research is needed to establish
      whether other factors also play a role.

PMID- 17217574
TI  - Predictors and dietary consequences of frequent intake of high-sugar, low
      nutrient foods in 1-year-old children participating in the ABIS study.
AB  - Foods rich in sugar have been suggested to contribute to the increasing
      prevalence of obesity in children. The aim of this report is to investigate the
      dietary pattern in 1-year-old children who frequently receive foods rich in sugar
      but low in nutrients and to study associated demographic and parental factors.
      During 1977-9, 21,700 infants were invited to participate in this prospective,
      population-based, longitudinal cohort study. Screening questionnaires were
      completed for 16,070 infants after delivery. Follow-up questionnaires from 10,762
      children at 1 year of age are included in the analysis. It was found that 24% of
      the children received sweets/pastries more often than one or two times per week.
      They had a higher intake of French fries, potato crisps and cream as well as a
      lower intake of fruit and vegetables. A frequent intake of sugar-rich, low
      nutrient foods was significantly associated with several maternal factors (high
      intake of sweets/pastries during pregnancy, young age, mother living alone) as
      well as presence of older siblings. Maternal smoking during pregnancy and
      maternal overweight were of borderline significance. Parental education level was
      inversely associated with the frequency of intake of sweets/pastries in the
      child. Children who frequently receive sweets/pastries also have an otherwise
      unfavourable dietary pattern. Several parental and demographic factors were
      associated with this feeding pattern, especially high intake of sweets/pastries
      during pregnancy. Screening of pregnant women for risk predictors like
      consumption of sweets/pastries, young age and smoking could be possible ways of
      identifying children at future risk for low dietary quality.

PMID- 17217575
TI  - Equivalence of information from single frequency v. bioimpedance spectroscopy in
      bodybuilders.
AB  - In bioelectrical impedance spectroscopy (BIS), it is assumed that the current
      path is only extracellular at the lowest frequencies and that it is both extra-
      and intracellular at the highest frequencies. We tested validity of BIS
      assumptions in bodybuilders who have an increased intracellular volume due to
      hypertrophy of muscle fibres. The study was observational cross-sectional in a
      study group of thirty professional bodybuilders compared with thirty control
      subjects. Resistance (R) and reactance (Xc) vector components fitting the Cole's
      arc with BIS (SFB3 analyser) were compared with components at 50 kHz frequency.
      The average Cole's arc in bodybuilders was significantly smaller and shifted to
      the left in the R-Xc plane (both R and Xc values were smaller at any individual
      frequency). The ratio of Xc at 5 kHz and Xc at the characteristic frequency was
      70% in bodybuilders and 64% in control subjects, indicating a huge intracellular
      flow of the electric current at low frequencies in both groups (expected ratio
      close to 0 if the current path was extracellular). As a consequence of a common
      path, the correlation coefficient between R values at 50 kHz and at other
      frequencies (from 0 to infinity) was 0.94 to 1.00. The correlation between total
      body water estimated with BIS or with R at 50 kHz was 0.98. Hence, there was
      equivalence between information provided by the vector components R and Xc at 50
      kHz and that provided by 496 correlated vectors that were measured with BIS.

PMID- 17217576
TI  - Long-term dietary compensation for added sugar: effects of supplementary sucrose
      drinks over a 4-week period.
AB  - The long-term physiological effects of refined carbohydrates on appetite and mood
      remain unclear. Reported effects when subjects are not blind may be due to
      expectations and have rarely been studied for more than 24 h. The present study
      compared the effects of supplementary soft drinks added to the diet over 4 weeks
      on dietary intake, mood and BMI in normal-weight women (n 133). Subjects were
      categorised as 'watchers' or 'non-watchers' of what they ate then received
      sucrose or artificially sweetened drinks (4 x 250 ml per d). Expectancies were
      varied by labelling drinks 'sugar' or 'diet' in a counter-balanced design.
      Sucrose supplements provided 1800 kJ per d and sweetener supplements provided 67
      kJ per d. Food intake was measured with a 7 d diary and mood with ten single
      Likert scales. By 4 weeks, sucrose supplements significantly reduced total
      carbohydrate intake (F(1,129) = 53.81; P<0.001), fat (F(2,250) = 33.33; P<0.001)
      and protein intake (F(2,250) = 28.04; P<0-001) compared with sweetener
      supplements. Mean daily energy intake increased by just under 1000 kJ compared
      with baseline (t (67 df) = 3.82; P< 0.001) and was associated with a non
      significant trend for those receiving sucrose to gain weight. There were no
      effects on appetite or mood. Neither dietary restraint status as measured by the
      Dutch Eating Behaviour Questionnaire nor the expectancy procedure had effects.
      Expectancies influenced mood only during baseline week. It is concluded that
      sucrose satiates, rather than stimulates, appetite or negative mood in normal
      weight subjects.

PMID- 17217577
TI  - The B'Active programme for overweight primary school children in Glasgow:
      determining the prevalence of overweight and obesity and piloting an activity
      intervention.
AB  - The aim of this study was to determine the prevalence of overweight and obesity
      in primary school children in Glasgow and to evaluate a pilot activity programme
      for overweight and obese children. BMI was measured in 1548 children. Overweight,
      obesity and severe obesity were defined as BMI > or =85th, 95th and 98th centile,
      respectively. Overweight and obese children were then invited to participate in a
      10-week school-based activity programme. The programme was evaluated by recording
      weekly attendance, intensity (using the Children's Effort Rating Scale) and
      enjoyment (scale 1-10). Focus groups were used to explore the experiences and
      views of the children, teachers, coaches and parents. Of the 1548 children, 31.4%
      were overweight, 19.1% were obese and 12.4% were severely obese; 38% of those
      invited attended the activity programme. Weekly programme attendance was 83%
      (range 56-99%). Mean enjoyment rating (scale 1-10) was 8 for boys and 9 for
      girls. The intensity of activity sessions were rated 'very easy' by boys and
      'just feeling a strain' by girls. Common themes emerging from the focus groups
      related to perceived positive and negative aspects of the programme (fun,
      concerns about stigmatising children); physical and psychological outcomes
      (fitter, more confident); and future recommendations (involve parents). In
      summary, the prevalence of overweight and obesity was high. The activity
      programme was successful in terms of attendance and enjoyment, and overall views
      of the initiative were positive and there was compelling support for its
      continuation.

PMID- 17217582
TI  - Single molecule Raman scattering.

PMID- 17217578
TI  - Determinants of childhood overweight and obesity in China.
AB  - In order to investigate the determinants of childhood overweight and obesity in
      China, the prevalence of overweight (including obesity) was compared according to
      different dietary and physical activity patterns and parental body weight status.
      A total of 6826 children aged 7-17 years from the 2002 China National Nutrition
      and Health Survey were included in the study. Information for dietary intake was
      collected using three consecutive 24-h recalls by trained interviewers. The
      amounts of cooking oil and condiments consumed were weighed. An interview
      administered 1-year physical activity questionnaire was used to collect physical
      activity information. The results showed that the heavier the parental
      bodyweight, the higher the overweight prevalence in children. The prevalence
      ratio increased if parent(s) were overweight and/or obese, up to 12.2 if both
      parents were obese. Overweight children consumed significantly more dietary
      energy, protein and fat, but less carbohydrate than their normal weight
      counterparts. On average, overweight children spent 0.5 h less on
      moderate/vigorous activities and 2.3 h more on low intensity activities per week.
      The following prevalence ratios were statistically significant: walking to and
      from school (0.6); moderate/vigorous activities > or =45 min/d (0.8); low
      intensity physical activities >2 h/d (1.3); the consumption of > or =25 g/d
      cooking oil (1.4); > or =200 g/d meat and meat products consumption (1.5); > or
      =100g/d dairy products (1.8). After adjustment for parental body weight status
      and socioeconomic status, only cooking oil consumption and walking to and from
      school remained significantly related to child overweight. In conclusion,
      parental weight status is an import-ant determinant. Fat intake, low intensity
      activities and active transport to/from school may be suitable entry points for
      overweight prevention among Chinese school children.

PMID- 17217583
TI  - Bulk Raman analysis of pharmaceutical tablets.
AB  - We compare and contrast two Raman collection geometries, backscattering and
      transmission, to identify their potential for monitoring the bulk chemical
      composition of turbid media. The experiments performed on pharmaceutical tablets
      confirm the expected strong bias of the backscattering Raman collection towards
      surface layers of the probed sample. However, this bias is largely absent with
      the transmission geometry, exhibiting gross insensitivity to the depth of
      impurities within the sample. The results are supported by Monte-Carlo
      simulations. The applicability of transmission geometry to tablets without any
      thinning is possible because of long migration times of Raman photons in non
      absorbing powder media. The absolute measured intensity of the Raman signal was
      only 12 times lower in transmission geometry compared with backscattering
      geometry for a standard paracetamol tablet with a thickness of 3.9 mm. This makes
      detection relatively straightforward, and detectable Raman signals were observed
      even after propagation through three paracetamol tablets. Given its properties
      and instrumental simplicity, the transmission method is particularly well suited
      to the on-line analysis of bulk content of tablets in pharmaceutical
      applications.

PMID- 17217584
TI  - Raman spectra of biological samples: A study of preprocessing methods.
AB  - In this study preprocessing of Raman spectra of different biological samples has
      been studied, and their effect on the ability to extract robust and quantitative
      information has been evaluated. Four data sets of Raman spectra were chosen in
      order to cover different aspects of biological Raman spectra, and the samples
      constituted salmon oils, juice samples, salmon meat, and mixtures of fat,
      protein, and water. A range of frequently used preprocessing methods, as well as
      combinations of different methods, was evaluated. Different aspects of regression
      results obtained from partial least squares regression (PLSR) were used as
      indicators for comparing the effect of different preprocessing methods. The
      results, as expected, suggest that baseline correction methods should be
      performed in advance of normalization methods. By performing total intensity
      normalization after adequate baseline correction, robust calibration models were
      obtained for all data sets. Combination methods like standard normal variate
      (SNV), multiplicative signal correction (MSC), and extended multiplicative signal
      correction (EMSC) in their basic form were not able to handle the baseline
      features present in several of the data sets, and these methods thus provide no
      additional benefits compared to the approach of baseline correction in advance of
      total intensity normalization. EMSC provides additional possibilities that
      require further investigation.

PMID- 17217585
TI  - Orientation-independent spectra for biaxial systems in polarized Raman
      microspectrometry.
AB  - From an extension of the scattering intensity expressions in polarized Raman
      macrospectrometry to the case of micro-Raman backscattering experiments, we have
      established theoretical expressions to calculate orientation-independent
      intensity sums. This approach makes use of the K2 Raman invariant and of
      correction coefficients due to integration of the Raman scattering over the cone
      of collection of the objective lens, and it may be applied to uniaxial as well as
      to biaxial symmetry systems. The intensity sums thus obtained are expected to be
      orientation insensitive and allow one to compare conformational changes in
      various biaxially oriented polymer samples, either amorphous and/or
      semicrystalline thin films. As application examples we have compared the
      polarized Raman results obtained for various biaxially oriented amorphous and
      semicrystalline polystyrene (PS), poly(ethylene terenaphthalate) (PEN), and
      poly(ethylene terephthalate) (PET) thin film samples with their respective
      "isotropic spectrum" and have considered the different main conformational
      changes in related polymer systems. The method is thus tested on these
      macromolecular systems and appears quite successful in providing evidence for the
      molecular conformational changes without interferences from spectral
      contributions due to orientation.

PMID- 17217587
TI  - Degradation of curcumin dye in aqueous solution and on ag nanoparticles studied
      by ultraviolet-visible absorption and surface-enhanced Raman spectroscopy.
AB  - The chemical degradation of curcumin (CU) in aqueous solution and on silver
      nanoparticles was studied by means of ultraviolet (UV)-visible absorption and
      surface-enhanced Raman (SERS) spectroscopy at different pH levels and upon light
      irradiation. CU undergoes a chemical degradation in aqueous solution mainly when
      the pH is increased. The CU degradation is catalytically enhanced in the presence
      of Ag nanoparticles. In general, CU degradation implies two steps: (1) the
      breakdown of the interring chain connecting the two CU aromatic side rings,
      producing smaller phenolic compounds rich in carboxylate groups, and (2)
      polymerization of the resulting phenolic products, giving rise to phenolic
      polymeric products. The degradation-polymerization mechanism can be modulated
      depending on the experimental conditions. The chemical photoproducts resulting
      from the visible light irradiation are similar to the polycatechol products
      obtained when catechol is adsorbed on Ag nanoparticles.

PMID- 17217586
TI  - Multilayer enhanced gold film over nanostructure surface-enhanced Raman
      substrates.
AB  - We have developed a novel class of gold multilayer, surface-enhanced Raman
      scattering (SERS) substrates that are capable of enhancing SERS signals by 15.3
      fold over conventional gold film over nanostructure (GFON) SERS substrates,
      making them comparable in sensitivity to optimized silver film over nanostructure
      (SFON) substrates, while providing the long-term stability obtained from gold.
      They are fabricated by depositing 10 A thick silver oxide islands on conventional
      GFON substrates, followed by deposition of a second continuous gold layer. The
      silver oxide layer acts as a dielectric spacer between the two continuous gold
      films and produces significantly enhanced SERS signals, as compared to optimized
      single layer substrates of the same geometry or comparable substrates prepared by
      deposition of silver islands that are not oxidized. In addition to the enhanced
      sensitivity of these multilayer substrates, they also exhibit long SERS active
      shelf-lives (i.e., months), with no measurable degradation in SERS enhancement,
      and relative standard deviations in SERS enhancement of less than 5.2% across the
      substrate's surface.

PMID- 17217588
TI  - Water diffusion and sorption-induced swelling as a function of temperature and
      ethylene content in ethylene-vinyl alcohol copolymers as determined by attenuated
      total reflection fourier transform infrared spectroscopy.
AB  - Attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopy
      has been advantageously used to carry out a simultaneous study of the effect of
      temperature on sorption, diffusion, swelling rate, and swelling rate factor of
      ethylene-vinyl alcohol (EVOH) cast films with three different ethylene contents
      (29, 38, and 44 mol % of ethylene). While the sorption and swelling levels at
      equilibrium did not appear to be affected by temperature in the temperature range
      studied, the effect of increasing ethylene content was seen to largely decrease
      the sorption-induced swelling. It should be noted that all samples showed
      significant levels of swelling ( approximately 60% in the copolymer with lowest
      ethylene content), suggesting that films obtained by solution-casting generate
      polymer morphologies that are far more prone to uptake water than typical melt
      extruded ones. It was also observed that increasing the ethylene content led to a
      reduction of the "effective" D value, while raising the temperature increased
      diffusion and swelling rate factor. The activation energies obtained for the
      diffusion of water were relatively low and similar to the typical energy barrier
      required to break hydrogen bonding interactions, suggesting that water molecules
      diffuse very easily across the film due to its high chemical affinity with the
      polymer matrix.

PMID- 17217589
TI  - Infrared kinetic/structural studies of barrier reformation in intact stratum
      corneum following thermal perturbation.
AB  - Stratum corneum, the outermost layer of the epidermis, constitutes the main
      barrier to permeability in skin. As such, it has been the target of many
      approaches for transdermal drug delivery based on methods involving transient
      modifications of the barrier. An infrared (IR) spectroscopic method has been
      developed to monitor the kinetics of barrier restoration following an external
      perturbation. In the current case, temperature perturbation was selected as a
      convenient means to induce structural changes in the barrier. The method is based
      on the observation that the ordered lipid phases of the barrier in isolated human
      stratum corneum exist in part in orthorhombically packed subcells. Such phases
      display a characteristic splitting of the CH2 rocking vibrations with component
      frequencies at 720 and 729 cm(-1). The latter is reliably diagnostic for
      orthorhombic phases and is markedly reduced in intensity following a thermal
      perturbation to 55 degrees C. The kinetics of barrier recovery following
      quenching to either 25 degrees C or 30 degrees C were monitored by tracking the
      restoration of the 729 cm(-1) band intensity. The kinetics were dominated by
      exponential growth in the initial stages, followed by linear increases at longer
      times. The half lives for exponential growth regimes were 52.4 h for the 25
      degrees C quench and 13.8 h for the 30 degrees C quench. These values are in
      reasonable accord with those determined with more phenomenological approaches,
      typically based on restoration of some barrier function. This novel method for
      monitoring structural reorganization kinetics in intact stratum corneum can
      readily be extended to evaluate barrier recovery following a variety of
      treatments used to enhance drug delivery.

PMID- 17217590
TI  - Use of fourier transform infrared spectroscopy to follow the heterocumulene aided
      thermal dehydration of phthalic and naphthalic acids.
AB  - Fourier transform infrared (FT-IR) spectroscopy has been successfully employed to
      follow the formation of phthalic anhydride and 1,8-naphthalic anhydride on
      heating their corresponding acids. The effects of three heterocumulenes,
      cyanamide, dicyandiamide, and sodium cyanate, on the temperature of formation of
      the anhydrides were also investigated using this method. It was found that the
      carbodiimides cyanamide and dicyandiamide dramatically lowered the temperature at
      which thermal dehydration of the acid led to anhydride formation. It was noted
      that cyanamide had a stronger catalytic effect than dicyandiamide, presumably due
      to the electron-withdrawing effect of the amidine group. Sodium cyanate was also
      found to promote the thermal dehydration of the acids to form the corresponding
      anhydrides. Under more severe conditions, phthalic acid anhydride formed is seen
      to react further, leading to the formation of phthalimide. The discrepancy
      between the products obtained with cyanamide and sodium cyanate leads to the
      conclusion that, unlike earlier claims, imide formation is not due to the
      reaction of the anhydride with the urea formed but with sodium cyanate itself.
      However, only the phthalic anhydride five-membered ring system is sufficiently
      reactive towards the CNO- nucleophile to form the imide; the six-membered 1,8
      naphthalic anhydride system does not react in this way.

PMID- 17217591
TI  - Modification of kaolinite surfaces through mechanochemical activation with
      quartz: A diffuse reflectance infrared fourier transform and chemometrics study.
AB  - Studies of kaolinite surfaces are of industrial importance. One useful method for
      studying the changes in kaolinite surface properties is to apply chemometric
      analyses to the kaolinite surface infrared spectra. A comparison is made between
      the mechanochemical activation of Kiralyhegy kaolinites with significant amounts
      of natural quartz and the mechanochemical activation of Zettlitz kaolinite with
      added quartz. Diffuse reflectance infrared Fourier transform (DRIFT) spectra were
      analyzed using principal component analysis (PCA) and multi-criteria decision
      making (MCDM) methods, the preference ranking organization method for enrichment
      evaluations (PROMETHEE) and geometrical analysis for interactive assistance
      (GAIA). The clear discrimination of the Kiralyhegy spectral objects on the two PC
      scores plots (400-800 and 800-2030 cm(-1)) indicated the dominance of quartz.
      Importantly, no ordering of any spectral objects appeared to be related to
      grinding time in the PC plots of these spectral regions. Thus, neither the
      kaolinite nor the quartz are systematically responsive to grinding time according
      to the spectral criteria investigated. The third spectral region (2600-3800 cm(
      1), OH vibrations), showed apparent systematic ordering of the Kiralyhegy and, to
      a lesser extent, Zettlitz spectral objects with grinding time. This was
      attributed to the effect of the natural quartz on the delamination of kaolinite
      and the accompanying phenomena (i.e., formation of kaolinite spheres and water).
      The mechanochemical activation of kaolinite and quartz, through dry grinding,
      results in changes to the surface structure. Different grinding times were
      adopted to study the rate of destruction of the kaolinite and quartz structures.
      This relationship (i.e., grinding time) was classified using PROMETHEE and GAIA
      methodology.

PMID- 17217592
TI  - Noninvasive near-infrared blood glucose monitoring using a calibration model
      built by a numerical simulation method: Trial application to patients in an
      intensive care unit.
AB  - We have applied a new methodology for noninvasive continuous blood glucose
      monitoring, proposed in our previous paper, to patients in ICU (intensive care
      unit), where strict controls of blood glucose levels are required. The new
      methodology can build calibration models essentially from numerical simulation,
      while the conventional methodology requires pre-experiments such as sugar
      tolerance tests, which are impossible to perform on ICU patients in most cases.
      The in vivo experiments in this study consisted of two stages, the first stage
      conducted on healthy subjects as preliminary experiments, and the second stage on
      ICU patients. The prediction performance of the first stage was obtained as a
      correlation coefficient (r) of 0.71 and standard error of prediction (SEP) of
      28.7 mg/dL. Of the 323 total data, 71.5% were in the A zone, 28.5% were in the B
      zone, and none were in the C, D, and E zones for the Clarke error-grid analysis.
      The prediction performance of the second stage was obtained as an r of 0.97 and
      SEP of 27.2 mg/dL. Of the 304 total data, 80.3% were in the A zone, 19.7% were in
      the B zone, and none were in the C, D, and E zones. These prediction results
      suggest that the new methodology has the potential to realize a noninvasive blood
      glucose monitoring system using near-infrared spectroscopy (NIRS) in ICUs.
      Although the total performance of the present monitoring system has not yet
      reached a satisfactory level as a stand-alone system, it can be developed as a
      complementary system to the conventional one used in ICUs for routine blood
      glucose management, which checks the blood glucose levels of patients every few
      hours.

PMID- 17217593
TI  - Optimization of discriminant partial least squares regression models for the
      detection of animal by-product meals in compound feedingstuffs by near-infrared
      spectroscopy.
AB  - This paper evaluates two multivariate strategies for classifying near-infrared
      (NIR) spectroscopic data for the detection of animal by-product meals (henceforth
      generically termed AbP) as an ingredient in compound feedingstuffs.
      Classification models were developed to discriminate between the presence and
      absence of animal-origin meals in compound feeds using two forms of discriminant
      partial least squares (PLS) regression: the algorithms PLS1 and PLS2. The
      training set comprised 433 commercial feeds, of which 148 contained AbP and the
      other 285 were stated to be AbP-free. Since the initial set contained unequal
      numbers of each class, the effect of this imbalance was analyzed by applying the
      same algorithms to a training set containing equal numbers of AbP-free and AbP
      containing samples. The best classification model (97.42% of samples correctly
      classified), obtained with PLS2, that showed less sensitivity to the use of class
      unbalanced sets, was externally validated using a set of 18 samples (10 AbP
      containing and 8 AbP-free); all samples were correctly classified, except for one
      AbP-free sample that was classified as containing AbP (false positive). The
      results suggest that the application of PLS discriminant analysis to NIR
      spectroscopic data enables detection of AbP, a feed ingredient banned since the
      bovine spongiform encephalopathy (BSE) crisis; this confirms the value of NIRS
      qualitative analysis for product authentication purposes.

PMID- 17217594
TI  - Near-infrared characterization on the secondary structure of regenerated Bombyx
      mori silk fibroin.
AB  - Several advantages of the near-infrared (NIR) technique in the characterization
      of the secondary structure of regenerated Bombyx mori silk fibroin are
      demonstrated. Silk fibroin films with thicknesses ranging from 50 to 300 microm
      are suitable for the NIR measurement. The bands due to hydrogen-bonded water are
      independent in the NIR spectra and facilitate our investigation of the amide
      region. Analysis of the combination modes of amide groups in the NIR spectra
      could lead to a profile of conformation ratio of silk fibroin, which was
      supported by nuclear magnetic resonance (NMR) observations.

PMID- 17217595
TI  - Spectrally resolved frequency domain analysis of multi-fluorophore systems
      undergoing energy transfer.
AB  - Complex systems of fluorophores undergoing energy transfer can exhibit a variety
      of anomalous lifetime behavior when probed with frequency domain methods. When
      presented in traditional apparent lifetime format the data from such systems can
      exhibit "nodal" behavior in which the computed lifetime approaches +/-infinity.
      The location of the nodes is system and frequency dependent. In addition, simpler
      systems, not undergoing energy transfer, show ill behavior in the region of zero
      lifetime (tau(m)) and long lifetime (tau(pi)) due to noise in typical
      measurements. Here, we systematically investigate systems of multiple
      fluorophores with and without energy transfer to provide insight into frequency
      domain investigations of complex systems of fluorophores. The results of
      simulations are compared to data collected from a multi-fluorophore system
      designed to exhibit fluorescence resonance energy transfer (FRET) using imaging
      spectroscopic fluorescence lifetime imaging microscopy (ISFLIM). The results are
      applicable to both cuvette and imaging arrangements.

PMID- 17217596
TI  - Luminescence dynamics of terbium monodipicolinate in ethyl ammonium nitrate.
AB  - Energy level dynamics are experimentally examined for terbium monodipicolinate
      dissolved in ethyl ammonium nitrate (EAN). The luminescence lifetime, the
      luminescence risetime, and the absorption spectrum of terbium monodipicolinate in
      EAN are measured. The risetime of luminescence in terbium dipicolinate is
      experimentally shown to be nonzero and measurable. A dynamic model is presented
      that describes the evolution of terbium dipicolinate luminescence in EAN. The
      long risetime in the model is caused by a resonance between the 5E6 state in the
      terbium cation and the lowest triplet state (T1) in the dipicolinate anion.
      Bacterial endospore components dissolved in EAN are used to check the time
      resolution of the experimental apparatus. EAN is discussed partly because it is a
      room-temperature ionic liquid (RTIL), which is a class of solvents that may be
      useful for detecting bacterial endospores in the atmosphere.

PMID- 17217597
TI  - Extended-range spectroscopic pH measurement using optimized mixtures of dyes.
AB  - The spectroscopic technique for pH measurement is a well-established laboratory
      technique that can give high-accuracy pH values. Recent studies have shown the
      advantage of this technique over standard potentiometric methods for pH
      measurements in fresh water and seawater and also at high temperatures and
      pressures. However, a limitation of the spectroscopic technique is that a single
      pH dye is sensitive only over a narrow pH range. We have developed optimized dye
      mixtures that are both sensitive and accurate over a broad pH range. The
      measurement is robust and simple, requires a minimum of two wavelengths, and is
      independent of the volume of the dye mixture added. Optimization of the dye
      mixture formulation to maximize accuracy in a broad range of pH involves varying
      both the dye type and its mole fraction and also accounting for spectral noise.
      This technique has been successfully applied for in situ pH measurements of
      oilfield formation waters.

PMID- 17217598
TI  - Tuning D* with modified thermal detectors.
AB  - We report on the fabrication and characterization of a modified thermopile
      detector that has a spectral detectivity, D*, primarily determined by the
      absorbance of a polymer film. This was done by coating the detector with a metal
      mirror, followed by the polymer film, so that the film absorbances are
      responsible for most thermal conversion. The detector is designed to tailor the
      spectral response of optical systems more specifically to analytes in order to
      improve precision in methods such as multivariate optical computing and simple
      photometry. Interference effects in the thin-film response are eliminated by the
      textured surface of the silicon thermopile, which makes the spectral response
      relatively simple. The maximum detectivity due to a 1-micrometer-thick film is
      found to be 20% of the detectivity of the original wide-band detector at 10 Hz
      modulation frequency. We estimate the thermal diffusion length in the polymer at
      10 Hz to be 40 micrometers. We also suggest that the detectivity of the modified
      detector can be approximated as the product of the D* of the underlying thermal
      detector and the absorbance of the modifying film, provided the modulation
      frequency is low and interference effects are defeated.

PMID- 17217599
TI  - A millisecond infrared stopped-flow apparatus.
AB  - In this paper, we have described a stopped-flow apparatus that is capable of
      measuring infrared kinetics in the amide I' region of a protein's vibrational
      spectrum. The dead time of this setup, determined by the reducing reaction of 2,6
      Dichlorophenolindophenol by L-ascorbic acid, is between 6 to 15 ms, depending on
      the flow rate. Therefore, this stopped-flow IR method provides a means of
      measuring infrared kinetics in a time window that is not easily accessible to
      other mixing-based IR techniques. Using this apparatus, we have studied the
      alkaline transition of cytrochrome c and have found that this conformational
      event proceeds in a biphasic manner. The characteristic time constants of these
      two phases were determined to be 68 +/- 20 ms and 624 +/- 37 ms, respectively.

PMID- 17217600
TI  - Chain of custody for samples of live crude oil using visible-near-infrared
      spectroscopy.
AB  - In order to design oil production facilities and strategies, it is necessary to
      acquire crude oil samples from subsurface formations in oil wells in so-called
      openhole prior to production. In some environments, such as deepwater production
      of oil, decisions of huge economic importance are based on such samples. To date,
      there has been little quality control to verify that the crude oils collected in
      the sample bottles and analyzed up to a year later in the laboratory have any
      relation to the actual crude oils in the subsurface reservoirs. These high
      pressure samples can undergo myriad deleterious alterations. Here, we introduce
      the chain-of-custody concept to the oilfield. The visible-near-infrared spectrum
      of the crude oil is measured in situ in the wellbore at the point of sample
      acquisition. This spectrum is compared with the spectrum measured on putatively
      the same fluid in the laboratory at the start of laboratory sample analysis.
      First, quantitative assessment is made of whether the fluid in the (high
      pressure) sample bottle remains representative of formation fluids. Second, any
      specific changes in the spectrum of the fluid can be related to possible process
      control failures. Here, the entire process of chain of custody is proven. The
      chain of custody process can rapidly become routine in the petroleum industry,
      thereby significantly improving the reliability of any process that depends on
      fluid property determination.

PMID- 17217601
TI  - Observation of a penetration depth gradient in attenuated total reflection
      fourier transform infrared spectroscopic imaging applications.

PMID- 17217603
TI  - The proportions of Down's syndrome pregnancies detected prenatally in England and
      Wales from 1989 to 2004.
AB  - OBJECTIVES: The proportion of Down's syndrome pregnancies detected prenatally in
      England and Wales is lower in younger mothers than in older mothers. This paper
      examines the reasons for this apparent age inequality. METHODS: We used data from
      the National Down Syndrome Cytogenetic Register (NDSCR) to examine the time trend
      of the proportion of Down's syndrome pregnancies diagnosed prenatally according
      to maternal age over the years 1989-2004 in England and Wales. RESULTS: A lower
      proportion of younger mothers had their Down's syndrome pregnancy detected
      prenatally than older mothers; however, this gap has been closing over time. For
      example, for mothers under 25 years of age only 13% of Down's syndrome
      pregnancies were detected prenatally from 1989 to 1992, with this figure rising
      to 34% in 2001-2004, compared with proportions of 74% in both periods for mothers
      over 44 years of age. A lower uptake of screening among younger women could not
      explain these differences. The differences in detection rates of the screening
      methods according to maternal age, particularly of the older screening tests,
      could account for these differences. CONCLUSIONS: The closing gap between the
      proportions of younger and older women having their affected pregnancy prenatally
      diagnosed is a confirmation of the improvement of screening methods over time.

PMID- 17217604
TI  - Validation plots in antenatal screening for Down's syndrome.
AB  - OBJECTIVE: To validate empirically the accuracy of antenatal Down's syndrome
      screening using the Integrated test, to compare this with other screening tests
      (including the Integrated test with the addition of cross trimester [CT] marker
      ratios) and to suggest how such validation analyses should be presented and
      interpreted. METHODS: Using data from 7809 unaffected and 27 Down's syndrome
      pregnancies that had had an Integrated test, risk estimates for various screening
      tests (maternal age, Double, Triple, Quadruple, Combined, Integrated and serum
      Integrated tests) that use Integrated test markers were categorized according to
      quintile categories of risk estimates of the 27 affected pregnancies. For each
      screening test, the median risk estimate for each category was plotted against
      the observed prevalence within each category. Such validation plots were also
      produced for the Integrated test with CT marker ratios by measuring the level of
      the serum markers in the trimester of pregnancy not already measured in stored
      samples of all affected and a one-in-five sample of unaffected pregnancies. The
      robustness of the method was assessed by repeating the analysis for the
      Integrated test after re-classifying affected pregnancies with low risk estimates
      as unaffected, simulating the underascertainment of cases. RESULTS: The
      validation plots (i) confirmed the accuracy of risk estimation for the different
      tests (by how close the points lay to the line of identity between predicted risk
      and observed prevalence), (ii) demonstrated the differences in screening
      performance of the different tests (by the range of risk spanned by the points
      and, in particular, the separation between the points representing the lowest
      risk and the next point), and (iii) are robust to underascertainment of affected
      pregnancies (by having little influence on the closeness of the points to the
      line of identity). CONCLUSION: The validation plot is a useful, simple and robust
      way to assess the validity of new screening methods, to assess the accuracy of
      risk estimation and to audit the performance of screening programmes.

PMID- 17217605
TI  - Marriage and cancer prevention: does marital status and inviting both spouses
      together influence colorectal cancer screening participation?
AB  - OBJECTIVES: This study examined the influence of marital status and inviting both
      partners together on participation in colorectal cancer screening. SETTING: Data
      were from a subset of participants from the UK Flexible Sigmoidoscopy Trial (1996
      1999). METHODS: Marital status was self-reported, and co-invitation of partner
      was obtained from the trial database. Screening intentions were assessed in
      16,527 adults aged 55-64 years. Attendance was recorded in the 4130 respondents
      who were subsequently invited. RESULTS: Multivariate analyses, controlling for
      age and educational level, indicate that married (or cohabiting) people have more
      positive intentions (odds ratio [OR] = 1.26; 95% confidence interval [CI] 1.14
      1.38) and higher attendance rates at screening (OR = 1.23; 95% CI 1.04-1.45) than
      nonmarried people. After adjusting for the marriage effect, inviting partners
      together (co-invitation) significantly increased screening intentions among women
      (OR = 1.17; 95% CI 1.04-1.31) but not men (OR = 0.97; 95% CI 0.85-1.10). Co
      invitation significantly increased attendance at screening in both genders (OR =
      1.34; 95% CI 1.14-1.58). CONCLUSIONS: In this age group, married adults are more
      likely to participate in colorectal cancer screening than the non-married, and
      inviting both members of a couple together further increases screening uptake.
      The positive effect of marriage was as strong for women as men.

PMID- 17217606
TI  - The challenge of evaluating annual mammography screening for young women with a
      family history of breast cancer.
AB  - It has been recommended that women aged 40-49 years with a significant family
      history of breast cancer should be offered annual mammography screening
      (http://www.nice.org.uk). An observational study known as FH01
      (http://www.screeningservices.org/btw/fh01/index.asp) is evaluating this policy
      in a cohort of 6000 women at moderately increased risk of breast cancer due to
      family history. The main aims are to assess the likely impact on breast cancer
      mortality and cost-effectiveness. Measuring these outcomes is challenging in an
      environment where a randomized trial is not feasible and there is no natural
      comparison group. In this paper, we present some approaches to estimating
      effectiveness and the planned analyses. These involve comparison of disease stage
      and likely consequent breast cancer mortality in the cohort offered screening
      with that estimated in the absence of screening. The estimation uses observed
      outcomes in external populations and estimated outcomes for the hypothetical
      situation where screening had not taken place.

PMID- 17217607
TI  - Relationship between the method of detection and prognostic factors for breast
      cancer in a community with a screening programme.
AB  - OBJECTIVES: To analyse and compare the prognostic factors of breast cancer in the
      target population of our community-screening programme as a function of the
      method of detection and to analyse the differences in the prognostic factors as a
      function of the patient's age and the screening episode. SETTING: A Breast Cancer
      Screening Programme (BCSP) in Northeast Spain. METHODS: Observational study of
      all primary malignant breast lesions diagnosed in a woman between 50 and 69 years
      of age between 18 October 1995 and 31 December 2002. The 16 centres that women
      from the target population might have attended were contacted. RESULTS: A total
      of 225 (37.2%) of the lesions included were diagnosed through the BCSP, 59 (9.7%)
      interval cancers were detected, and 321 (53.1%) were detected through other
      circuits. Node involvement was significantly lower in the lesions detected at
      screening (32%) in comparison to the interval cancers (41.8%) and those detected
      through other circuits (47.5%). A significantly larger percentage of the interval
      tumours (28.6%) and the lesions diagnosed outside the BCSP (22.1%) scored >5.4 on
      the Nottingham Prognostic Index (NPI) than those diagnosed within the programme
      (10.9%). The relation between the NPI and the detection method was only
      statistically significant in the 65-69-year-old age group. The NPI score of the
      tumours detected by the BCSP showed a statistically significant association with
      age. CONCLUSION: This analysis has shown notable differences in some prognostic
      factors for breast cancer according to the method of detection. Association
      between age and the a priori prognosis of the malignant lesions arises.

PMID- 17217608
TI  - Number and characteristics of breast cancer cases diagnosed in four periods in
      the screening interval of a biennial population-based screening programme.
AB  - OBJECTIVE: To describe the distribution and prognostic tumour characteristics of
      interval breast cancers diagnosed in four periods after index screen (1-6, 7-12,
      13-18 and 19+ months) in a population-based screening programme inviting women
      aged 50-69 years to biennial screening. SETTING: The Norwegian Breast Cancer
      Screening Programme (NBCSP) Methods: In all, 848 interval breast cancer cases
      were diagnosed in 437,235 screening examinations. The distribution and prognostic
      tumour characteristics of the interval cancers diagnosed in four periods in the
      screening interval will be described. Proportions and rates will be compared by
      chi(2)-test. RESULTS: A total of 70% of the interval cancers in the NBCSP were
      diagnosed in the second year of the interval. Except for tumour size (P = 0.027),
      we found no evidence of adverse prognostic breast characteristics (grade, lymph
      node involvement, oestrogen and progesterone receptor positive) in invasive
      tumours diagnosed during the second versus the first year of the screening
      interval (Chi square P > 0.05 for all). The prognostic characteristics of the
      tumours did not differ by age groups. It was a decreasing interval cancer rate
      per 10,000 women-years by age. CONCLUSION: The risk of interval cancer increases
      by time after index screen, and 70% of the interval cancers in the NBCSP were
      diagnosed in the second year of the interval. Prognostic histological tumour
      characteristics did not differ by time after index screen, thus mean sojourn time
      (tumour growth rate) seems important for stating an optimal screening interval in
      a population-based screening programme.

PMID- 17217609
TI  - The effect of data quality at the time of introduction of population-based
      screening on the estimate of programme impact using surrogate outcome measures.
AB  - OBJECTIVE: The aim of this study was to examine the availability and quality of
      surrogate outcome measure data to enable the evaluation of the breast screening
      programme. As the observed effect on mortality of a screening programme occurs
      many years after the introduction of screening, surrogate outcome measures offer
      an attractive alternative, allowing estimates of the effect to be calculated
      earlier. METHODS: The exercise was undertaken by the Oxford Cancer Intelligence
      Unit and the Cancer Screening Evaluation Unit in collaboration with cancer
      registries in England, Scotland and Wales. RESULTS: The conclusion of the
      exercise was that, in general, the available data quality was insufficient to
      allow a precise estimate of the overall mortality reduction from breast screening
      to be made using surrogate measures. CONCLUSIONS: When a screening programme is
      started, it is vital that forward planning is undertaken to ensure that the
      necessary information is ready to be collected before the start of the programme.
      The use of surrogate measures is dependent on high-quality data in the uninvited
      group of women (pre-screening or from a staggered start over areas), and
      improving data quality over time after the start of the programme is of very
      limited value for a surrogate measures approach. The collection of appropriate
      high-quality information before the programme starts is, therefore, critical to
      measuring the success of the programme. Cancer registries and staff within the
      screening programme need to be ready to collect the appropriate data before the
      introduction of a screening programme. The exercise undertaken therefore has
      important implications where new screening programmes are being considered.

PMID- 17217610
TI  - Public awareness of human papillomavirus.
AB  - OBJECTIVES: The main objective of this study was to review the evidence relating
      to the level of awareness of human papillomavirus (HPV) in the general population
      and the implications for the potential introduction of HPV vaccination and HPV
      testing as part of screening. METHODS: PubMed search performed on terms: 'HPV
      education', 'HPV awareness' 'Genital Warts Awareness' Results: Public awareness
      of HPV is generally very low, particularly with respect to its relation to
      abnormal smears and cervical cancer although knowledge levels vary to some extent
      according to sociodemographic characteristics. There is also much confusion
      around which types cause warts and the types that can cause cancer. The sexually
      transmissible nature of the infection is of major concern and confusion to women.
      CONCLUSIONS: Due to the lack of current awareness of HPV, significant education
      initiatives will be necessary should HPV vaccination and/or HPV testing be
      introduced. Organized edification of health-care workers and the media, who
      constitute the two most preferred sources of information, will be crucial.

PMID- 17217611
TI  - Acceptability of unsupervised HPV self-sampling using written instructions.
AB  - OBJECTIVES: The study measured the acceptability of self-sampling for human
      papillomavirus (HPV) testing in the context of cervical cancer screening. Women
      carried out self-sampling unsupervised, using a written instruction sheet.
      SETTING: Participants were women attending either a family planning clinic or a
      primary care trust for routine cervical screening. METHODS: Women (n = 902)
      carried out self-sampling for HPV testing and then a clinician did a routine
      cervical smear and HPV test. Immediately after having the two tests, participants
      completed a measure of acceptability for both tests, and answered questions about
      ease of using the instruction sheet and willingness to use self-sampling in the
      future. RESULTS: The majority of women found self-sampling more acceptable than
      the clinician-administered test, but there was a lack of confidence that the test
      had been done correctly. Significant demographic differences in attitudes were
      found, with married women having more favourable attitudes towards self-sampling
      than single women, and Asian women having more negative attitudes than women in
      other ethnic groups. Intention to use self-sampling in the future was very high
      across all demographic groups. CONCLUSION: Self-sampling for HPV testing was
      highly acceptable in this large and demographically diverse sample, and women
      were able to carry out the test alone, using simple written instructions.
      Consistent with previous studies, women were concerned about doing the test
      properly and this issue will need to be addressed if self-sampling is introduced.
      More work is needed to see whether the demographic differences we found are
      robust and to identify reasons for lower acceptability among single women and
      those from Asian background.

PMID- 17217612
TI  - Response to 'Receiver operating characteristics of the prostate-specific antigen
      test in an unselected population'.

PMID- 17217615
TI  - Differential expression of claudin family proteins in mouse ovarian serous
      papillary epithelial adenoma in aging FSH receptor-deficient mutants.
AB  - Ovarian cancer is a deadly disease with long latency. To understand the
      consequences of loss of follicle-stimulating hormone receptor (FSH-R) signaling
      and to explore why the atrophic and anovulatory ovaries of follitropin receptor
      knockout (FORKO) mice develop different types of ovarian tumors, including serous
      papillary epithelial adenoma later in life, we used mRNA expression profiling to
      gain a comprehensive view of misregulated genes. Using real-time quantitative
      reverse transcription-polymerase chain reaction, protein analysis, and cellular
      localization, we show, for the first time, in vivo evidence that, in the absence
      of FSH-R signaling, claudin-3, claudin-4, and claudin-11 are selectively
      upregulated, whereas claudin-1 decreases in ovarian surface epithelium and tumors
      in comparison to wild type. In vitro experiments using a mouse ovarian surface
      epithelial cell line derived from wild-type females reveal direct hormonal
      influence on claudin proteins. Although recent studies suggest that cell junction
      proteins are differentially expressed in ovarian tumors in women, the etiology of
      such changes remains unclear. Our results suggest an altered hormonal environment
      resulting from FSH-R loss as a cause of early changes in tight junction proteins
      that predispose the ovary to late-onset tumors that occur with aging. More
      importantly, this study identifies claudin-11 overexpression in mouse ovarian
      serous cystadenoma.

PMID- 17217616
TI  - Enhanced cell survival of gastric cancer cells by a novel gene URG4.
AB  - Upregulated gene 4 (URG4), a novel gene located on 7 chromosome (7p13), was found
      to contribute to hepatocarcinogenesis. However, the role of URG4 in the gastric
      carcinogenesis still remains unclear. In the present study, URG4 was found by
      immunohistochemistry to be upregulated in human gastric cancer tissues compared
      with matched adjacent nonneoplastic tissues. The proliferating cell nuclear
      antigen index is higher in gastric cancer tissues with high URG4 expression than
      in those with low URG4 expression. The growth of GES-1 cells, which are
      immortalized human gastric epithelial mucosa cells with baseline URG4 expression,
      was accelerated by URG4 induction. Downregulation of URG4 through URG4 small
      interfering RNA (siRNA) in SGC7901 and MKN28 cells, which had high endogenous
      URG4 expression, suppressed cell proliferation in both of these cells. URG4-siRNA
      also inhibited the proliferation of SGC7901 and MKN28 cells in soft agar and
      tumor formation in nude mice. Overexpression of URG4 in GES cells upregulated
      cyclin D1, whereas repression of URG4 in SGC7901 and MKN28 cells downregulated
      cyclin D1. The data suggested that URG4 played an important role in the
      development of human gastric cancer by regulating the expression of cyclin D1 and
      might be used as a potential therapeutic target for gastric cancer.

PMID- 17217617
TI  - Loss of function of the candidate tumor suppressor prox1 by RNA mutation in human
      cancer cells.
AB  - The importance of genetic mutations in carcinogenesis has been recognized, and it
      has been proposed that aberrant mutation of mRNA may represent a novel oncogenic
      principle. Here we report that the mRNA of a homeobox gene prox1, a candidate
      tumor suppressor, suffers adenosine-to-inosine nucleotide conversion and loses
      tumor-suppressive functions in a subset of human cancers. Expression of Prox1 was
      reduced in pancreatic cancers, and the extent of reduction correlated with
      progression of tumor differentiation. A-to-G base change was found in prox1 cDNA
      taken from human cancer cells, but not in corresponding genomic DNA. We mapped
      four common mutation sites in prox1 gene, and the same four sites were mutated in
      human clinical samples from several cancers. Tetracycline-induced wild-type (wt)
      Prox1 in tumor cells inhibited transforming activity and cellular proliferation.
      However, mutant Prox1 with the four common sites altered from A to G lost these
      inhibitory functions. In mice, xenografts of tumor cells with tetracycline
      induced wt-Prox1 formed tumor masses significantly more slowly than control
      tumors, whereas mutated Prox1 had no effect. These findings may point to a
      pivotal role of the RNA mutation of prox1 gene in the pathogenesis of human
      cancer progression.

PMID- 17217618
TI  - In vivo imaging of molecularly targeted phage.
AB  - Rapid identification of in vivo affinity ligands would have far-reaching
      applications for imaging specific molecular targets, in vivo systems imaging, and
      medical use. We have developed a high-throughput method for identifying and
      optimizing ligands to map and image biologic targets of interest in vivo. We
      directly labeled viable phage clones with far-red fluorochromes and comparatively
      imaged them in vivo by multichannel fluorescence ratio imaging. Using Secreted
      Protein Acidic and Rich in Cysteine (osteonectin) and vascular cell adhesion
      molecule-1 as model targets, we show that: 1) fluorescently labeled phage retains
      target specificity on labeling; 2) in vivo distribution can be quantitated
      (detection thresholds of approximately 300 phage/mm(3) tissue) throughout the
      entire depth of the tumor using fluorescent tomographic imaging; and 3)
      fluorescently labeled phage itself can serve as a replenishable molecular imaging
      agent. The described method should find widespread application in the rapid in
      vivo discovery and validation of affinity ligands and, importantly, in the use of
      fluorochrome-labeled phage clones as in vivo imaging agents.

PMID- 17217620
TI  - Loss of p12CDK2-AP1 expression in human oral squamous cell carcinoma with
      disrupted transforming growth factor-beta-Smad signaling pathway.
AB  - We examined correlations between TGF-beta1, TbetaR-I and TbetaR-II, p12(CDK2
      AP1), p21(WAF1), p27(KIP1), Smad2, and p-Smad2 in 125 cases of human oral
      squamous cell carcinoma (OSCC) to test the hypothesis that resistance to TGF
      beta1-induced growth suppression is due to the disruption of its signaling
      pathway as a consequence of reduced or lost p12(CDK2-AP1). Immunoreactivity for
      TbetaR-II decreased in OSCC with increasing disease aggressiveness; however, no
      differences were observed for TbetaR-I and TGF-beta1. The expression of TbetaR-II
      significantly correlated with p12(CDK2-AP1) and p27(KIP1) (P < .001 and P < .01,
      respectively). Furthermore, there was a significant relationship between TbetaR
      II expression and p-Smad2 (P < .001). The in vivo correlation of the levels of
      TbetaR-II, p12(CDK2-AP1), and p27(KIP1) was confirmed in normal and OSCC cell
      lines. Additionally, in vitro analysis of TGF-beta1-treated cells showed that TGF
      beta1 treatment of normal keratinocytes suppressed cell growth with upregulation
      of p-Smad2, p12(CDK2-AP1), and p21(WAF1) expression, whereas there was no effect
      on OSCC cell lines. These results provide evidence of a link between a disrupted
      TGF-beta-Smad signaling pathway and loss of induction of cell cycle-inhibitory
      proteins, especially p12(CDK2-AP1) in OSCC, which may lead to the resistance of
      TGF-beta1 growth-inhibitory effect on OSCC.

PMID- 17217619
TI  - Altered expression of ZO-1 and ZO-2 in Sertoli cells and loss of blood-testis
      barrier integrity in testicular carcinoma in situ.
AB  - Carcinoma in situ (CIS) is the noninvasive precursor of most human testicular
      germ cell tumors. In normal seminiferous epithelium, specialized tight junctions
      between Sertoli cells constitute the major component of the blood-testis barrier.
      Sertoli cells associated with CIS exhibit impaired maturation status, but their
      functional significance remains unknown. The aim was to determine whether the
      blood-testis barrier is morphologically and/or functionally altered. We
      investigated the expression and distribution pattern of the tight junction
      proteins zonula occludens (ZO) 1 and 2 in normal seminiferous tubules compared to
      tubules showing CIS. In normal tubules, ZO-1 and ZO-2 immunostaining was observed
      at the blood-testis barrier region of adjacent Sertoli cells. Within CIS tubules,
      ZO-1 and ZO-2 immunoreactivity was reduced at the blood-testis barrier region,
      but spread to stain the Sertoli cell cytoplasm. Western blot analysis confirmed
      ZO-1 and ZO-2, and their respective mRNA were shown by RT-PCR. Additionally, we
      assessed the functional integrity of the blood-testis barrier by lanthanum tracer
      study. Lanthanum permeated tight junctions in CIS tubules, indicating disruption
      of the blood-testis barrier. In conclusion, Sertoli cells associated with CIS
      show an altered distribution of ZO-1 and ZO-2 and lose their blood-testis barrier
      function.

PMID- 17217621
TI  - The proteasome inhibitor MG-132 protects hypoxic SiHa cervical carcinoma cells
      after cyclic hypoxia/reoxygenation from ionizing radiation.
AB  - INTRODUCTION: Transient hypoxia and subsequent reoxygenation are common phenomena
      in solid tumors that greatly influence the outcome of radiation therapy. This
      study was designed to determine how varying cycles of hypoxia/reoxygenation
      affect the response of cervical carcinoma cells irradiated under oxic and hypoxic
      conditions and whether this could be modulated by proteasome inhibition.
      MATERIALS AND METHODS: Plateau-phase SiHa cervical carcinoma cells in culture
      were exposed to varying numbers of 30-minute cycles of hypoxia/reoxygenation
      directly before irradiation under oxic or hypoxic conditions. 26S Proteasome
      activity was blocked by addition of MG-132. Clonogenic survival was measured by a
      colony-forming assay. RESULTS: Under oxic conditions, repeated cycles of
      hypoxia/reoxygenation decreased the clonogenic survival of SiHa cells. This
      effect was even more pronounced after the inhibition of 26S proteasome complex.
      In contrast, under hypoxic conditions, SiHa cells were radioresistant, as
      expected, but this was increased by proteasome inhibition. CONCLUSIONS:
      Proteasome inhibition radiosensitizes oxygenated tumor cells but may also protect
      tumor cells from ionizing radiation under certain hypoxic conditions.

PMID- 17217622
TI  - SAG/ROC-SCF beta-TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a
      mechanism of apoptosis protection.
AB  - Skp1-cullin-F-box protein (SCF) is a multicomponent E3 ubiquitin (Ub) ligase that
      ubiquitinates a number of important biologic molecules such as p27, beta-catenin,
      and IkappaB for proteasomal degradation, thus regulating cell proliferation and
      survival. One SCF component, SAG/ROC2/Rbx2/Hrt2, a RING finger protein, was first
      identified as a redox-inducible protein, which, when overexpressed, inhibited
      apoptosis both in vitro and in vivo. We report here that sensitive to apoptosis
      gene (SAG), as well as its family member ROC1/Rbx1, bound to the proinactive form
      of caspase-3 (pro-caspase-3). Binding was likely mediated through F-box protein,
      beta-transducin repeat-containing protein (beta-TrCP), which binds to the first
      38 amino acids of pro-caspase-3. Importantly, beta-TrCP1 expression significantly
      shortened the protein half-life of pro-caspase-3, whereas expression of a
      dominant-negative beta-TrCP1 mutant with the F-box domain deleted extended it. An
      in vitro ubiquitination assay showed that SAG/ROC-SCF(beta-TrCP) promoted
      ubiquitination of pro-caspase-3. Furthermore, endogenous levels of pro-caspase-3
      were decreased by overexpression of SAG/ROC-SCF(beta-TrCP) E3 Ub ligases, but
      increased on siRNA silencing of SAG, regulator of cullin-1 (ROC1), or beta-TrCPs,
      leading to increased apoptosis by etoposide and TNF-related apoptosis-inducing
      ligand through increased activation of caspase-3. Thus, pro-caspase-3 appears to
      be a substrate of SAG/ROC-SCF(beta-TrCP) E3 Ub ligase, which protects cells from
      apoptosis through increased apoptosis threshold by reducing the basal level of
      pro-caspase-3.

PMID- 17217623
TI  - Heparanase localization and expression by head and neck cancer: correlation with
      tumor progression and patient survival.
AB  - Heparanase is an endoglycosidase that specifically cleaves heparan sulfate (HS)
      side chains of HS proteoglycans, the major proteoglycans in the extracellular
      matrix and cell surfaces. Traditionally, heparanase activity was implicated in
      cellular invasion associated with angiogenesis, inflammation, and cancer
      metastasis. More recently, heparanase upregulation was documented in an
      increasing number of primary human tumors, correlating with reduced postoperative
      survival rate and enhanced tumor angiogenesis. In the present study, we examined
      the expression of heparanase in squamous cell carcinoma of the head and neck by
      means of immunostaining, and we correlated expression levels with patient
      outcome. The intensity and extent of heparanase staining correlated with tumor
      stage (P = .049 and P = .027, respectively), and the extent of staining further
      correlated with tumor grade (P = .047). Moreover, heparanase expression inversely
      correlated with patient status at the end of the study (P = .012). Notably,
      heparanase localization was found to be an important parameter for patient
      status. Thus, 63% of patients with nuclear staining, compared to 19% of patients
      with cytoplasmic staining (P = .0043), were alive, indicating that nuclear
      localization of the enzyme predicts a favorable outcome.

PMID- 17217624
TI  - Expression and effect of inhibition of the ubiquitin-conjugating enzyme E2C on
      esophageal adenocarcinoma.
AB  - Ubiquitin-dependent proteolysis of cyclins plays a critical role in cell cycle
      progression and tumorigenesis. We examined the expression of ubiquitin
      conjugating enzyme E2C (UBE2C) during progression from Barrett's metaplasia to
      esophageal adenocarcinoma (EA) and the effects of targeting this enzyme on EA
      derived cell lines. Using oligonucleotide microarrays UBE2C expression was
      elevated in 73% (11 of 15) of EAs relative to Barrett's metaplasia. Tissue
      microarray showed elevated UBE2C in 70% (7 of 10) of dysplastic samples and in
      87% (58 of 67) of tumors relative to metaplastic samples. Transfection of
      dominant-negative UBE2C into Seg-1 cells decreased proliferation (P = .04) and
      increased mitotic arrest compared to vector controls (63.5% vs 6.8%; P < .001).
      Transfection of UBE2C small interfering RNA also caused inhibiton of cell
      proliferation and distortion of the cell cycle, with maximal increase of G(2)
      cells (155% of mock cells) at 72 hours and of S-phase cells (308% of mock cells)
      at 24 hours. Treatment of Seg-1 cells with the proteasome inhibitor MG-262 (1 nM
      1 microM) showed decreased proliferation (P = .02). EA-derived cells expressing
      UBE2C are sensitive to treatment with MG-262 and to silencing of UBE2C,
      suggesting that patients with EAs overexpressing UBE2C may benefit from agents
      targeting this ubiquitin-conjugating enzyme.

PMID- 17217626
TI  - Genomic profiling of hormone-naive lymph node metastases in patients with
      prostate cancer.
AB  - The progression of organ-confined prostate cancer to metastatic cancer is
      inevitably fatal. Consequently, identification of structural changes in the
      genome and associated transcriptional responses that drive this progression is
      critical to understanding the disease process and the development of biomarkers
      and therapeutic targets. In this study, whole genome copy number changes in
      genomes of hormone-naive lymph node metastases were profiled using array
      comparative genomic hybridization, and matched primaries were included for a
      subset. Matched primaries and lymph node metastases showed very similar copy
      number profiles that are distinct from primary tumors that fail to metastasize.

PMID- 17217625
TI  - Notch signaling enhances nestin expression in gliomas.
AB  - Recent findings suggest that Notch signaling is active in brain tumors and stem
      cells, and that stem cells or cells with progenitor characteristics contribute to
      brain tumor formation. These stem cells are marked by expression of several
      markers, including nestin, an intermediate filament protein. We have studied how
      the Notch signaling pathway affects nestin expression in brain tumors. We find
      that Notch receptors and ligands are expressed in vitro and in human samples of
      glioblastomas, the highest grade of malignant gliomas. In culture, Notch activity
      activates the nestin promoter. Activation of the Notch pathway also occurs in a
      glioblastoma multiforme mouse model induced by Kras, with translational
      regulation playing a role in Notch expression. Combined activation of Notch and
      Kras in wild-type nestin-expressing cells leads to their expansion within the
      subventricular zone and retention of proliferation and nestin expression.
      However, activation of Notch alone is unable to induce this cellular expansion.
      These data suggest that Notch may have a contributing role in the stem-like
      character of glioma cells.

PMID- 17217628
TI  - Bariatric surgery claims - a medico-legal perspective.
AB  - The increase in frequency of bariatric surgery has been accompanied by an
      increase in litigation involving patients and practitioners in this emerging
      field. With much being written about the medical aspects of bariatric surgery,
      the legal and risk management perspective of these procedures is now getting
      increased attention. This article examines from a legal and risk management
      perspective the issue of patient selection, informed consent, postoperative
      management, the use of promotional materials and other issues that can result in
      a doctor or facility being sued.

PMID- 17217629
TI  - New device for the introduction of a circular stapler in laparoscopic gastric
      bypass surgery.
AB  - BACKGROUND: In laparoscopic Roux-en-Y gastric bypass (LRYGBP) surgery, the
      anastomosis between the gastric pouch and the jejunum can be performed using a
      circular stapler, as described in the original publication by Wittgrove in 1994.
      The introduction of the circular stapler through the thick abdominal wall in
      morbidly obese patients can be challenging. To overcome the difficulties of this
      task, a new device was developed and its use is presented. METHOD: The new device
      has the shape of a trocar tip which can be mounted on the circular stapler,
      giving it the properties of a trocar. Therefore, easier introduction into the
      abdominal cavity is feasible. The use of the device was assessed analyzing the
      data of a prospective database, comparing patient groups operated without the
      device (n=301) and patients operated with the device (n=100). RESULTS: The groups
      were comparable in age, sex, BMI and number of previous abdominal operations. The
      wound infection rate at the site of stapler introduction decreased from 6.6% to
      1% (P=0.035). The overall operating time, hospital stay and complication rate
      were unchanged. CONCLUSION: The new device proved to be useful in daily practice
      and enabled an easier stapler introduction with fewer wound infections.

PMID- 17217630
TI  - Anesthetic management of morbidly obese and super-morbidly obese patients
      undergoing bariatric operations: hospital course and outcomes.
AB  - BACKGROUND: Although the implications for the anesthetic and perioperative care
      of severely obese patients undergoing weight loss operations are considerable,
      current anesthetic management of super-obese (SO) patients (BMI > or =50
      kg/m(2)), including super-super-obese (BMI > or =60) derives from experience with
      morbidly obese (MO) patients (BMI 40-49.9 kg/m(2)). We compared anesthetic and
      perioperative data of SO patients and MO patients undergoing weight loss
      operations to evaluate if anesthetic management influenced outcome. METHODS: A
      retrospective analysis was performed on data from 150 consecutive patients (119
      MO, 31 SO) undergoing bariatric surgery between May 2000 and March 2005. Data
      analyzed included preoperative anesthetic assessment, anesthetic management,
      postoperative care, and intra- or postoperative complications. RESULTS: There
      were no differences in anesthetic management or in postoperative course or
      outcome between MO and SO patients. Intraoperative surgical complications
      occurred in 26% (n=8) in the SO group and 14% (n=15) in the MO group (P<0.01).
      CONCLUSIONS: No differences in outcome occurred between MO and SO patients
      undergoing bariatric operations under similar anesthetic management. Anesthesia
      for weight loss surgery can be safely performed on SO patients with the
      understanding that these patients are not at risk per se due to their higher BMI.
      The degree of obesity influenced only the incidence of intraoperative surgical
      complications.

PMID- 17217631
TI  - The value of pulmonary function testing prior to bariatric surgery.
AB  - BACKGROUND: Pulmonary function tests (PFTs) are often abnormal in the morbidly
      obese and improve after bariatric surgery. Our aim was to determine the utility
      of obtaining preoperative PFTs in assessing postoperative risk. METHODS: 146
      consecutive patients undergoing open bariatric surgery were analyzed. Patients
      were divided into those who had postoperative complications (Group A, n=27) and
      those who did not (Group B, n=119). PFTs and BMI were compared between Groups A
      and B. PFT parameters are reported as the median percentage of age-matched
      controls. RESULTS: Patients in Group A compared to Group B were heavier (BMI 58
      vs 51 kg/m(2), P=.001) and older (46 vs 40 years, P=.02) than those in group B.
      They had reduced forced vital capacity (80% vs 97%, P<.001) and forced expiratory
      volume in 1 second (84% vs 99%, P=.002). They also had reduced vital capacity
      (VC, 85% vs 102%, P<.001) and total lung capacity (89% vs 99%, P=.01). They had
      decreased maximal voluntary ventilation (93% vs 106%, P=.003). They had lower
      arterial pO(2) (76 mmHg vs 85 mmHg, P=.001) and higher arterial-alveolar gradient
      (23 vs 17, P=.007). The strongest predictors of postoperative complications on
      multivariate analysis were reduced VC (RR 2.29 for each 10% decrease in VC,
      P=.0007) and age (RR 6.4 for age >40 years, P=.01). CONCLUSIONS: PFTs help to
      predict complications after bariatric surgery. The greatest reduction in VC may
      occur in patients with central obesity, reflecting increased intrabdominal
      pressure and diminished chest wall compliance.

PMID- 17217632
TI  - Computerized baropodometry in obese patients.
AB  - BACKGROUND: Few studies have investigated the influence of obesity on the
      structural and functional performance of the feet, and its potential implications
      for the musculoskeletal system. Computerized baropodometric analysis (CPA) is a
      new investigation for the center of pressure, plantar surface area and plantar
      pressure while standing on the platform of a specialized apparatus. CPA is
      relevant to gait and posture, and may be important as well for postoperative
      musculoskeletal disorders. We investigated the biomechanical dysfunctions of foot
      pressure by means of CPA in bariatric and non-bariatric subjects. METHODS:
      Subjects (n=67, 71.6% females, age 40.8 +/- 13.8 years, BMI 31.4 +/- 11.0
      kg/m(2)) included obese (BMI 30.0-60.0 kg/m(2), n=27), overweight (BMI 25.0-29.9
      kg/m(2), n=12) and normal-weight controls (BMI 20.0-24.9 kg/m(2), n=28) of
      equivalent age and gender. Variables included center of pressure location,
      plantar ground contact area and pressure, and pressure patterns (maximum and
      average) in different regions of the foot, during quiet standing on the platform
      of the baropodometer. RESULTS: A significant increase was detected for peak
      pressure on forefoot and plantar ground contact area in the obese group, compared
      to control and overweight cases, during quiet standing. CONCLUSION: Excessive
      forefoot pressure and enlarged support area were a consequence of obesity,
      mirroring the efforts of the obese subject to acquire a wider and stronger
      support base. Although this is originally a physiological change, it may result
      in maladaptative and degenerative musculoskeletal consequences. Re-education
      exercises may be advised, in combination with bariatric surgery in the morbidly
      obese, aiming at restoration of normal gait and posture, as well as at
      minimization of stress damage to bones and joints in the axial skeleton.

PMID- 17217633
TI  - Laparoscopic adjustable gastric banding in patients > or =60 years old: is it
      worthwhile?
AB  - BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) is an effective
      treatment for morbid obesity in younger patients, leading to improvements in
      related co-morbidities and quality of life. Currently, little is known how these
      improvements apply to older patients. METHODS: A prospective review was conducted
      of patients > or =60 years old undergoing LAGB. Weight loss, complications,
      changes in Short Form-36 (SF-36) scores, and a comprehensive post-operative co
      morbidity, medication and quality of life questionnaire were used to assess
      performance. RESULTS: 40 patients with mean age 65.8 years (range 60-72) and
      preoperative mean BMI of 42.2 kg/m(2) (range 33-54) underwent LAGB from February
      2000 to September 2005. Mean excess weight lost at 2 years was 54%. 3
      complications (7.5%) occurred (1 slippage and 2 access-port infections). There
      were no perforations, erosions or deaths. After a mean postoperative interval of
      27 months, SF-36 scores improved significantly in 4 of 8 components and exceeded
      age-matched population controls in 3 components. Co-morbidity improvement was
      reported in 80% of patients with diabetes, 79% with dyslipidemia, 75% with
      obstructive sleep apnea, 72% with heartburn, 69% with hypertension, 60% with
      musculoskeletal pain, and 56% with anxiety/depression. Medication requirements
      reduced or ceased in 66% who required musculoskeletal analgesics, 43% of
      diabetics, 33% using bronchodilators, and 29% with hypertension. Sleep improved
      in 48%, self-esteem increased in 70%, and 72% had a better outlook on life. 82%
      were happy that they had undergone LAGB, and 91% would recommend LAGB to other
      older people. CONCLUSION: LAGB offers safe and effective weight loss, and
      improvement in co-morbidities and in quality of life in morbidly obese patients
      aged > or =60 years.

PMID- 17217634
TI  - Hepatic histopathology of morbid obesity: concurrence of other forms of chronic
      liver disease.
AB  - BACKGROUND: Obesity is a chronic inflammatory condition, with related
      steatohepatitis and liver fibrosis. The authors analyzed the hepatic
      histopathology in morbidly obese patients and predictors of concurrence of
      clinical and/ or histopathologic findings of steatohepatitis with other forms of
      chronic liver disease. METHODS: The histopathologic findings in the liver of 160
      patients who were undergoing laparoscopic gastric bypass or gastric banding for
      morbid obesity, were examined. Clinical data (gender, age, BMI and associated
      diseases) and laboratory evaluation were obtained from the patient records. The
      degree of steatosis, ballooning degeneration, lobular inflammation and fibrosis
      were determined and scored. RESULTS: Among the patients, 62.5% (n=100) were
      females and 37.5% (n=60) were males, age 27 +/- 12 years, with mean BMI 43 +/-
      5.8 kg/m(2). 63, 54, 26, 15 and 2 patients were diagnosed as non-nonalcoholic
      steatohepatitis (non-NASH), NASH, chronic hepatitis B (CHB), alcoholic
      steatohepatitis and chronic hepatitis C (CHC), respectively. The prevalence of
      NASH was 33.8%, of which 5 patients (9.2%) had bridging fibrosis, but no
      cirrhosis was found in the NASH group. The prevalence of CHB was 16.3%, of which
      3 patients (11.6%) had bridging fibrosis and/or cirrhosis. Multivariate analysis
      showed an association between steatosis and AST, ALT, GGT, C-peptide, insulin,
      HOMA-IR and adiponectin. The predictors of ballooning degeneration were serum
      sugar and AST, whereas the predictors of lobular inflammation were AST and ALT.
      There was a trend toward a correlation between abnormal liver function, insulin
      resistance, steatosis, liver cell injury and Mallory body in the NASH population.
      BMI, C-peptide, steatosis, ballooning degeneration and portal inflammation were
      significantly different between NASH and CHB groups, but only steatosis and
      ballooning degeneration were independent factors of NASH compared with CHB group
      after multivariate analysis. Overall, AST, AST/ALT ratio, uric acid and portal
      inflammation were independently associated with advanced fibrosis, while only
      Mallory body (P=0.033) and portal inflammation (P=0.015) were significantly
      different between mild-moderate fibrosis and advanced fibrosis in the NASH
      patients. CONCLUSION: Hepatic steatosis, features of metabolic syndrome and liver
      cell injuries were common in morbidly obese patients. Abnormal liver function and
      portal inflammation were related to hepatic fibrosis. The coexistance of clinical
      and histologic features of steatohepatitis with another chronic liver disease may
      reflect the biological significance of the chronic inflammatory condition in the
      obese population, which requires further investigation.

PMID- 17217635
TI  - GLP-1 and changes in glucose tolerance following gastric bypass surgery in
      morbidly obese subjects.
AB  - BACKGROUND: It has been proposed, that the dramatic amelioration of type 2
      diabetes following Roux-en-Y gastric bypass (RYGBP) could by accounted for, at
      least in part, by changes in glucagon-like peptide-1 (GLP-1) secretion. However,
      human data supporting this hypothesis is scarce. METHODS: A 12-month prospective
      study on the changes in glucose homeostasis, and active GLP-1 in response to a
      standard test meal (STM) was conducted in 34 obese subjects (BMI 49.1+/-1.0
      kg/m(2)) who had different degrees of glucose tolerance: normal glucose tolerance
      (NGT, n=12), impaired glucose tolerance (IGT, n=12), and type 2 diabetes (n=10).
      RESULTS: At 6 weeks after RYGBP, despite the subjects still being markedly obese
      (BMI 43.5+/-0.9 kg/m(2)), fasting plasma glucose and HbA1c decreased in the 3
      study groups (P<0.05). Insulin sensitivity improved, but was still abnormal in a
      comparable proportion of subjects among groups (P=0.717). When insulin secretion
      was accounted for the prevailing insulin sensitivity, an increase was found in
      subjects with diabetes (P<0.05) although it remained lower compared to NGT- and
      IGT-subjects (P<0.01). At 12 months follow-up, no differences among groups were
      found in the evaluated glucose homeostasis parameters. Compared to baseline, at 6
      weeks the incremental AUC(0-120') of active GLP-1 in response to the STM
      increased in NGT and IGT (P<0.05) but not in subjects with diabetes (P=0.285).
      However, the GLP-1 response to a STM was comparable among groups at 12 months
      follow-up (P=0.887). CONCLUSIONS: 1) RYGBP was associated with an improvement but
      not complete restoration of glucose homeostasis at 6 weeks after surgery. 2) GLP
      1 is not a critical factor for the early changes in glucose tolerance.

PMID- 17217636
TI  - Body composition and metabolic changes following bariatric surgery: effects on
      fat mass, lean mass and basal metabolic rate: six months to one-year follow-up.
AB  - BACKGROUND: With the failure of traditional weight loss plans, bariatric surgery
      has become the treatment of choice for morbid obesity. The primary objective of
      this study was to track body composition and metabolic changes for 1 year
      following bariatric surgery. METHODS: 19 bariatric patients (14 female, 5 male)
      began the study and completed 12 months of testing, which included data
      collection within 1 week preoperatively and 1, 3, 6 and 12 months
      postoperatively. 2 female subjects were lost to the study between 6 months and 1
      year, resulting in 17 subjects (12 female, 5 male) completing the entire 12-month
      follow-up. Variables measured in this study included weight, lean body mass
      (LBM), fat mass (FM), % body fat and basal metabolic rate (BMR). RESULTS:
      Analysis of variance (ANOVA) using the general linear model indicated significant
      (P<.05) losses for weight, FM, and % fat for all time periods. Significant losses
      in LBM were observed in all time periods except 6-12 months, where no change in
      LBM (60.6 vs 61.1 kg) was observed. A significant decrease (P<.05) in BMR (2091
      vs 1758) was observed only from pre-surgery to 1 month post-surgery. Thereafter,
      there was no significant change in BMR (1758 vs 1647 vs 1651 vs 1674)
      respectively. Changes in LBM were correlated with changes in BMR at both 6-12
      months (r=.545, P=.024) and preoperatively to 12 months postoperatively (r=.608,
      P=.01). There were no significant changes in the BMR/LBM ratio over the 12-month
      period (28.3 vs 25.0 vs 27.3 vs 27.2 vs 27.4), indicating no adaptation of the
      body to an energy-conserving mechanism. CONCLUSION: Bariatric surgery appears to
      have been highly successful over the 12-month follow-up period, with 50.9 kg
      weight loss, 38.3 kg (75.2%) FM loss, and 12.6 kg (24.8%) LBM loss. The 417 kcal
      loss in BMR (2091 to 1674), while significant, was not greater than what would be
      predicted from loss of LBM.

PMID- 17217637
TI  - Psychosocial predictors of weight loss after bariatric surgery.
AB  - BACKGROUND: The authors investigated the predictive value of various parameters
      such as age, preoperative weight, eating behavior, psychiatric disorders, adverse
      childhood experiences and self-efficacy with regard to weight loss after gastric
      restrictive surgery. METHODS: After a minimum follow-up of 30 months (median
      follow-up 50 months; range 30-84 months), a questionnaire concerning extent of,
      satisfaction with, and consequences of weight loss was mailed to 220 morbidly
      obese female patients following laparoscopic Swedish adjustable gastric banding
      (SAGB). RESULTS: Questionnaires were completed and returned by 140 patients
      (63%). Average BMI loss was 14.6 kg/m(2). Most patients (85%) were happy with the
      extent of weight loss. Satisfaction with weight loss showed a significant
      correlation with extent of weight loss. BMI loss was greatest in the obese with
      an atypical eating disorder (20.0 kg/m(2)), and BMI loss was least in the obese
      with no eating-disordered behavior before surgery (13.4 kg/m(2)). Obese patients
      with two or more psychiatric disorders showed significantly less weight loss than
      did obese patients with one or no psychiatric disorder (BMI units 10.8 vs 14.0 vs
      16.1; P=.047). CONCLUSIONS: The findings indicate a less successful outcome for
      obese patients with psychiatric disorders (particularly adjustment disorders,
      depression and/or personality disorders), compared to patients not mentally ill.
      An eating disorder preceding surgery, however, was not a negative predictor of
      success following bariatric surgery. To improve outcome of bariatric surgery in
      obese patients with psychiatric disorders, more individual psychosocial
      intervention strategies are necessary.

PMID- 17217638
TI  - A prospective study of body dissatisfaction and concerns in extremely obese
      gastric bypass patients: 6- and 12-month postoperative outcomes.
AB  - BACKGROUND: Body image is a multifaceted construct commonly associated with
      obesity. This study examined changes in body dissatisfaction, and shape and
      weight concerns in bariatric surgery patients from baseline to 6 and 12 months
      post-surgery. METHODS: 109 extremely obese patients who underwent gastric bypass
      surgery completed the Body Shape Questionnaire (BSQ), and the Shape and Weight
      Concern subscales of the Eating Disorder Examination-Questionnaire (EDE-Q) at
      baseline, and 6 and 12 months post-surgery. RESULTS: Patients experienced
      substantial weight loss and reported statistically significant reductions in BSQ,
      and Shape and Weight Concern scores from baseline to 6 and 12 months post
      surgery. Improvements on the BSQ and Shape Concern scale were maintained between
      6 and 12 months post-surgery, while patients reported continued reductions in
      weight and Weight Concern scale scores. Moreover, at 6 and 12 months follow-up,
      over 80% of female patients had body image scores comparable to published norms.
      Correlations between change in BMI and the body image measures were variable, and
      degree of weight loss did not predict body image scores 6 or 12 months post
      surgery. CONCLUSIONS: Results from the present study illustrate significant and
      immediate post-surgical reductions in body dissatisfaction and concerns, along
      with weight loss in bariatric patients. Such improvements indicate a
      normalization of body image-related concerns in these patients, the majority of
      who remain overweight or obese despite the substantial post-surgical weight
      losses. Changes in weight and body image relate poorly to each other, suggesting
      that mediating factors may be involved.

PMID- 17217639
TI  - Expectations and outcomes with gastric bypass surgery.
AB  - BACKGROUND: Bariatric surgery is widely accepted as the effective treatment
      option for morbid obesity. However, the extant literature does not provide mental
      health clinicians with consistent guidance for evaluating candidates for surgery,
      nor for preparing patients for postsurgical adjustment. Among both bariatric
      clinicians and patients, there are commonly endorsed expectations about who will
      do well postoperatively and what the psychosocial impact of the surgery and
      weight loss will be. The current study surveyed our patient population regarding
      the accuracy of these expectations. METHODS: Medical charts were reviewed and
      surveys mailed to all 194 patients who had undergone the Roux-en-Y gastric bypass
      (RYGBP) at University of New Mexico Hospital prior to April 2003. Surveys
      explored patients' expectations and actual experiences with RYGBP and the
      subsequent changes in their physical and psychosocial status. RESULTS: Completed
      surveys received from 47.9% of the patients reported significant improvements in
      physical health, emotional status, and binge eating. These improvements were seen
      across the entire sample, regardless of the presence of preoperative
      psychological distress, and were unrelated to the degree of weight loss.
      Professional and non-romantic relationships benefited from the impact of weight
      loss, but romantic relationships appeared unaffected. There were no significant
      changes in occupational status. CONCLUSION: The impact of bariatric surgery
      appears sufficiently potent to negate whatever preoperative differences might
      otherwise affect weight management. It may be time for the field to cease its
      search for surgical outcome predictors and focus instead on improving
      postoperative support.

PMID- 17217640
TI  - Treatment choice and psychometric characteristics: differences between patients
      who choose bariatric surgical treatment and those who do not.
AB  - BACKGROUND: Among the treatment options offered to patients with severe obesity
      are surgery and psychotherapy plus dieting. The treatment choice may reflect
      differences in the psychology of these patients. The objective was to assess the
      psychopathological differences between patients with obesity who choose surgery
      and those who choose non-surgical treatment to lose weight. METHODS: 100 patients
      with obesity (50 in the non-surgical group [NS]; and 50 in the surgical group
      [S]; 41 women and 9 men in each group) completed the MMPI-2 and the EDI-2; for
      the latter, data from 21 S and 24 NS women were available. Comparisons were
      carried out through analysis of variance. RESULTS: The NS group scored higher on
      the Pa (paranoia) and Pt (psychasthenia) scales of the MMPI-2 compared to the S
      group. No differences were found on the EDI-2; however, both groups scored higher
      on the drive-for-thinness and body-dissatisfaction scales, and the NS group
      scored higher on the bulimia and ineffectiveness scales. CONCLUSION: The MMPI-2
      was able to distinguish between the NS and S groups, while the EDI-2 found
      significant eating-related psychopathology in both.

PMID- 17217641
TI  - Body contouring after biliopancreatic diversion.
AB  - BACKGROUND: From Nov 2001 to Mar 2006, 176 patients underwent body contouring
      plastic surgery after prior biliopancreatic diversion (BPD). Weight loss had
      varied from 30-100 kg. The plastic surgery targeted the arms (24 patients),
      breast (58), abdomen (62) and thighs (20), plus torsoplasty (12). METHODS: BPD is
      a "non-cosmetic" bariatric operation which results in malabsorption and
      subsequent major weight loss within 12 to 18 months. The typical "empty" aspect
      of the slimmed areas directed our surgical choices to specific techniques:
      brachioplasty, reduction mammaplasty and/or mastopexy (with or without prosthesis
      or "self-prosthesis" technique), thigh-lift, abdominoplasty and torsoplasty. We
      do not consider any liposuction technique suitable for this kind of patient,
      because of the specific histological changes caused by BPD. RESULTS: The
      metabolic discrepancies following BPD affect postoperative management of these
      patients. A higher incidence of complications has been reported, of both systemic
      and local nature; the local ones, common in the abdominal wall, convinced us to
      perform an arteriographic study preoperatively, to check anatomical alterations
      following the BPD. CONCLUSIONS: Although the characteristics of BPD patients
      limit the choices, we are satisfied with the results of cosmetic correction and
      quality of life. All the patients, without exception, noted a high rate of
      positive thinking and have undergone further body-contouring surgery (or plan to
      do so).

PMID- 17217642
TI  - Risk of venous thromboembolism and efficacy of thromboprophylaxis in hospitalized
      obese medical patients and in obese patients undergoing bariatric surgery.
AB  - BACKGROUND: Obesity is considered a highly prevalent risk factor for venous
      thromboembolism (VTE) in hospitalized patients. However, recommendations for VTE
      prophylaxis in obese patients are not clear. METHODS: To evaluate obesity as a
      risk factor for VTE in medical and bariatric patients and the efficacy of VTE
      prophylaxis, we performed a systematic review in MEDLINE, Cochrane Database of
      Systematic Reviews and LILACS from 1976 to 2006. Evidence was evaluated
      independently by 2 authors and presented descriptively. RESULTS: Of the 124
      studies found, 87 were excluded based on predefined criteria. There is no
      consensus among studies, but prospective cohorts show that obesity is associated
      with a higher risk of VTE in medical patients. There is evidence that the risk of
      VTE exceeds that attributable to the surgical procedure alone in bariatric
      surgery. Only 6 studies evaluated prophylactic methods (unfractionated heparin,
      low molecular weight heparin and sequential compression devices) in obese
      patients. Although these studies have some methodological flaws, they suggest
      efficacy of VTE prophylaxis in medical and surgical obese patients. CONCLUSIONS:
      Obesity is a risk factor for VTE in obese medical patients and patients
      undergoing bariatric surgery. Obesity appears to play an adjuvant role for the
      development of VTE in hospitalized patients with other risk factors. The small
      number of prospective trials in this population prevents a definite conclusion
      about the most effective and safe VTE prophylactic method for obese patients.
      Thus, randomized clinical trials to compare VTE prophylactic methods in obese
      patients are still highly warranted.

PMID- 17217643
TI  - Risk of upper gastrointestinal cancer after bariatric operations.
AB  - The authors discuss the potential influence of obesity surgery on the risk of
      cancer, focusing on the upper GI tract directly affected by operations. There is
      currently no substantiation for an increased risk of cancer after bariatric
      surgery, because there are only about 25 reports of subsequent cancer of the
      esophagus and the stomach. However, this review emphasizes the need to detect
      potential precancerous conditions before surgery. Candidates for postoperative
      endoscopic surveillance may include patients >15 years after gastric surgery, but
      also patients symptomatic for gastroesophageal reflux disease in whom a high
      incidence of Barrett's metaplasia has been reported. The greatest concern is a
      delay in diagnosis from inadequate investigation due to mistaking serious upper
      GI symptoms as a consequence of the past operation.

PMID- 17217644
TI  - Laparoscopic revision of the gastrojejunostomy for recurrent bleeding ulcers
      after past open revision gastric bypass.
AB  - Late complications of open gastric bypass can include malnutrition, weight gain,
      stomal stenosis, and recurrent bleeding ulcers. Herein, we describe the case of a
      woman who had recurrent bleeding ulcers, after an open revision of a stenotic
      gastric bypass. She now underwent an uneventful laparoscopic revision of her
      gastrojejunostomy and was discharged within 72 hours. Laparoscopic revision of a
      gastrojejunostomy, even after an open revision following an open gastric bypass,
      can be done safely.

PMID- 17217645
TI  - Treatment of gastro-jejunal leakage and fistulization after gastric bypass with
      coated self-expanding stents.
AB  - Leakage and fistulization of the gastro-jejunostomy have been the major drawback
      of Roux-en-Y gastric bypass (RYGBP) surgery. Most authors agree that operative
      treatment is the mainstay of therapy in patients with signs of sepsis. However,
      intestinal contents causing localized infection may impede healing of sutured
      leaks in some patients, and fistulas develop. Because the anastomosis cannot be
      disconnected or exteriorized for anatomical reasons, other forms of treatment
      have to be applied. The following case-reports describe a technique with
      implantation of coated self-expanding stents. Leakage of the gastro-jejunostomy
      occurred in one patient 3 days after RYGBP and resulted in formation of a
      fistula. A fistula developed in a second patient 63 days after RYGBP. Coated self
      extending stents were implanted endoscopically in both patients on postoperative
      days 19 and 67. Enteral nutrition could be started 6 days later. Stents were
      removed 2 months after implantation without problems. Weight loss and quality of
      life 7 and 21 months after stent removal have been excellent in both patients.
      Implantation of coated self-expanding stents was an effective and minimally
      invasive option for gastro-jejunal anastomotic fistulas after RYGBP where
      surgical repair was not possible. In these cases, application of stents allows
      septic source control without any other intervention.

PMID- 17217646
TI  - Exsanguinating hemorrhage following gastric erosion after laparoscopic adjustable
      gastric banding.
AB  - Laparoscopic adjustable gastric banding (LAGB) has become a common bariatric
      operation, because of its safety, laparoscopic friendliness, acceptable weight
      loss and absence of long-term adverse nutritional sequelae. Gastric erosion is
      one of the troublesome complications of gastric banding. The etiology and
      presentation of erosion remain obscure. We present a patient who complained of
      persistent pain 6 months after gastric banding. Endoscopy revealed the band to be
      normally situated, which was also confirmed on upper GI imaging. Despite this,
      the patient subsequently presented with massive GI hemorrhage and circulatory
      collapse due to erosion, which necessitated emergency laparotomy with retrieval
      of the band from within the gastric lumen. This case highlights the possible
      urgent presentation of erosion after gastric banding, which was hitherto
      considered to be a more insidious complication. A high index of clinical
      suspicion remains the mainstay of diagnosis.

PMID- 17217647
TI  - Band erosion and passage, causing small bowel obstruction.
AB  - A rare complication of adjustable gastric banding is reported. A 65-year-old man
      developed recurrent vomiting, epigastric pain, and small-bowel obstruction 13
      months after laparoscopic adjustable gastric banding for morbid obesity.
      Investigation revealed that the band had migrated completely into the gastric
      lumen and had passed far down the jejunum. The band was still connected by the
      tubing to the port chamber. By laparoscopy, the band was cut at the stomach, and
      removed via a jejunotomy. Postoperative course was uneventful. Complete band
      migration requires early removal of the band.

PMID- 17217648
TI  - Gastric bezoar complicating laparoscopic adjustable gastric banding with band
      slippage.
AB  - Gastric bezoars may develop in the proximal pouch after gastric restriction, eg.
      by laparoscopic adjustable gastric banding (LAGB). To date, only two centers have
      reported this rare complication. We report an additional case with band slippage,
      to emphasize that bezoars should be considered in the differential diagnosis in
      patients presenting with new onset nausea and vomiting after LAGB.

PMID- 17217650
TI  - [Importance of clinical and research work on metabolic syndrome in children].

PMID- 17217649
TI  - Long-term pulmonary complications after laparoscopic adjustable gastric banding.
AB  - Early pulmonary complications following laparoscopic adjustable gastric banding
      (LAGB) have been rare, while long-term pulmonary complications have not been
      reported. Herein, we report two patients who presented 2 and 3 years after LAGB
      with unexpected pulmonary complications. The first patient had aspiration
      pneumonia secondary to stomal obstruction and esophageal reflux. The second
      patient had left lobar pneumonia, in which the connecting catheter appeared as a
      linear structure within the consolidation. This may be due to migration of the
      connecting catheter through the diaphragm, piercing lung parenchyma. Both
      complications presented as asthma-like symptoms. Diagnosis could have been missed
      if not evaluated properly. A high index of suspicion and long-term follow-up are
      important for diagnosing such complications after LAGB.

PMID- 17217651
TI  - [Questions and answers on Protocols for Diagnosis and Treatment of Pediatric
      Gastroesophageal Reflux Disease (Draft)].

PMID- 17217652
TI  - [Postnatal and prenatal diagnosis of mucopolysaccharidosis type II (Hunter
      syndrome)].
AB  - OBJECTIVE: Mucopolysaccharidosis type II (MPS II, Hunter syndrome, OMIM 309900)
      is an X-linked recessive lysosomal storage disease resulting from a deficiency of
      iduronte-2-sulphate sulphatase (IDS). The present study aimed to establish an
      enzyme assay method for IDS activity for carrying out postnatal and prenatal
      diagnosis of MPS II by means of IDS activity assay on plasma, uncultured
      chorionic villi (CV) and cultured amniotic fluid cells (AF cell) using a new
      synthesized substrate. METHODS: A fluorigenic substrate (4-methylumbelliferyl
      alpha-iduronate-2-sulphate, MU-alpha-Idu-2S) was used for the assay of IDS
      activity. IDS activity in plasma was determined for diagnosis of the proband.
      Prenatal diagnosis in 10 pregnancies at risk was carried out according to IDS
      activity on uncultured CV at 11th week or on cultured AF cell at 18th week of
      gestation. At the same time, IDS activity was also determined in the maternal
      plasmas to observe the change of IDS activity in pregnancy. The fetal sex
      determination was performed by PCR amplification of the ZFX/ZFY genes. RESULT:
      The IDS activity in plasma of normal controls and obligate heterozygotes were
      240.2 - 668.2 nmol/(4 hxml) and 88.7 - 547.9 nmol/(4 hxml), respectively, while
      the enzyme activities in plasmas were in the range of 0.3 - 18.6 nmol/(4 hxml) in
      affected male. The IDS activities were 37.2 - 54.9 nmol/(4 hxmg protein) and 21.4
      - 74.4 nmol/(4 hxmg protein) in CV and cultured AF cells respectively. Out of 50
      suspected cases, 46 were diagnosed as having MPS II and 4 were excluded. Prenatal
      diagnosis was performed on 10 pregnancies at risk. Four of 5 male fetuses [IDS
      activity were 4.7, 1.8, 7.0 nmol/(4hxmg protein) in CV, 0.6 nmol/(4 hxmg protein)
      in AF cell] were diagnosed as having MPS II and the other 5 fetuses were normal
      females [IDS activity were: 48.7, 5.9, 25.2 nmol/(4 hxmg protein) in CV, 55.2,
      40.9 nmol/(4 hxmg protein) in AF cell]. Increased IDS activity was observed in
      plasma of the pregnant women with unaffected fetuses, while the IDS activity
      decreased in pregnancies with affected fetuses. IDS activity of one female fetus
      was very low [5.9 nmol/(4 hxmg protein)], but the IDS activity in maternal
      plasmas increased, this fetus was a normal female. CONCLUSIONS: The method using
      a synthesized fluorigenic 4-methylumbelliferyl-substrate was a sensitive, rapid
      and convenient assay of IDS activity and was reliable for early prenatal
      diagnosis. Determination of fetal sex would be helpful in excluding the female
      fetus with low IDS activity from being considered as an affected male fetus. It
      would be further helpful if IDS activity in maternal plasma was taken into
      account.

PMID- 17217653
TI  - [X chromosome inactivation patterns in patients with Rett syndrome and their
      mothers and the parental origin of the priority inactive X chromosome].
AB  - OBJECTIVE: Rett syndrome (RTT) is a severe childhood neurodevelopmental disorder
      mainly affecting females. The pathogenic gene is located at Xq28, which codes for
      the methyl-CpG-binding protein 2. MECP2 gene is affected by X chromosome
      inactivation (XCI). The different XCI patterns of females could affect the
      expression ratios of pathogenic gene, causing changes in clinical symptoms. In
      order to understand the XCI patterns in RTT patients and the relationship between
      XCI pattern, genotype and phenotype, the XCI patterns in patients with RTT and
      their mothers, the parental origin of the priority inactive X chromosome in RTT,
      and the relations of XCI patterns with genotype and phenotype in RTT cases were
      analyzed. METHODS: Genomic DNA was extracted from peripheral blood of 55 cases
      with RTT (52 with MECP2 mutations, 3 without mutations), 53 mothers of RTT cases
      and 48 normal female controls. DNA was digested with methylation sensitive
      restriction endonuclease Hpa II. Then the undigested and digested DNAs were
      amplified via PCR for the first exon of human androgen receptor (AR) gene. PCR
      products were analyzed by Genescan. RESULTS: The heterozygotic rates of AR gene
      were 82%, 77% and 83% in RTT patients, mothers and controls, respectively. XCI
      distribution pattern of RTT was different from that of the mothers and control, P
      < 0.05. More mothers and controls than RTT patients were in the area of XCI 50:50
      - 59:41. The differences between them were statistically significant (P < 0.05).
      No significant difference in XCI distribution patterns between mothers and the
      control groups was found (P > 0.05). Non-random XCI rates in the areas of XCI
      >or= 65:35 and >or= 80:20 were 53.35% and 17.8%, respectively, in RTT patients,
      compared with the mothers group (36.6%, 7.3%) and control group (35%, 10%), it
      was higher in RTT patients, but the difference was not statistically significant
      (P > 0.05). In 18 of 21 cases with XCI >or= 65:35, the priority inactive X
      chromosome was of paternal origin (85.7%). Variable XCI patterns were observed in
      the same gene mutation patients. The highly skewed XCI as well as the random XCI
      were found in patients with mild, severe and typical phenotype. The rate of
      highly skewed XCI in atypical patients was higher than that in typical RTT
      patients. The rate of highly skewed XCI in T158M was higher than the other type
      mutations. No highly skewed XCI was observed in cases with R133C mutation.
      CONCLUSION: The XCI distribution pattern of RTT patients was different from that
      of RTT mother and control groups. There was no significant difference in XCI
      distribution patterns between mothers and the control groups. It was not a main
      genetic pattern in RTT that mothers as the carriers to transmit the pathogenic
      gene to the patients. Non-random XCI was not the main XCI pattern in RTT
      patients. The priority inactive X chromosome was mainly of paternal origin. XCI
      could modify the clinical phenotype of RTT, but had limitations in explaining all
      the phenotypes manifested in RTT cases.

PMID- 17217654
TI  - [Questions and answers on massive proteinuria in the criteria for diagnosis of
      nephrotic syndrome].

PMID- 17217655
TI  - [A retrospective study on enzyme replacement therapy in patients with Gaucher
      disease].
AB  - OBJECTIVE: Gaucher disease is the most common lysosomal storage disorder. A
      deficiency of beta-glucocerebrosidase causes accumulation of the glucocerebroside
      in macrophages throughout the body. This study summarizes the effects of enzyme
      replacement therapy (ERT) with Imiglucerase in children with Gaucher disease.
      METHODS: Data from 72 patients (46 were male and 26 female, age ranged from 16
      months to 22 years, median 8 years and 8 months) who were treated in the hospital
      between May 1999 and October 2005 were collected and analyzed, 57 of the patients
      had type 1 Gaucher disease, 2 patients with type 2, and 13 patients with type 3.
      Twenty-two patients had undergone total splenectomy. Imiglucerase was given at an
      initial dose 60 U/kg body weight by intravenous infusion every 2 weeks. The dose
      was reduced to 45 U/kg when they had achieved the specified therapeutic goals
      after 2 years. Clinical outcome data of Imiglucerase treatment were collected
      using routine Gaucher clinical measures, including growth, hematology, liver and
      spleen 3-dimensional measurements, and skeletal assessments every 3 - 6 months.
      RESULTS: Three patients were lost to follow-up, 4 patients died, and 65 patients
      continued to receive the therapy. Hemoglobin and platelet levels of the patients
      with intact spleen increased most rapidly from the first 12 months of ERT (P <
      0.01). Hemoglobin level of the patients who had undergone splenectomy determined
      at 30 months of treatment was higher than that of baseline (P < 0.01), but
      platelet levels were not significantly different (P > 0.05). The volumes of the
      liver decreased after the 6 months of ERT, decreased in average by (39 +/- 17)%
      at 24 months (P < 0.01). The volumes of spleen decreased after the 12 months of
      ERT by (59 +/- 21)% at 24 months (P < 0.01). During the first 12 month, the
      height and weight of the patients who were 2 - 12 years old increased (8.6 +/-
      4.3) cm and (2.6 +/- 1.7) kg, respectively, and those of the patients who were 12
      - 18 years old increased (5.2 +/- 3.9) cm and (4.5 +/- 3.3) kg, separately. Bone
      pain reported by 16 patients relieved after 3 months of treatment. But
      radiological evidence of bone disease did not change. The signs and symptoms of
      CNS involvement in patients with type 2 and type 3 disease were not improved. No
      serious adverse events were reported. CONCLUSIONS: ERT with Imiglucerase could
      improve the quality of life of the patients with Gaucher disease by ameliorating
      the Gaucher disease-associated anemia, thrombocytopenia, organomegaly, growth
      retardation and bone pain.

PMID- 17217657
TI  - [Diagnostic tests for thyroid function and disorders].

PMID- 17217656
TI  - [Effect of recombinant human growth hormone on glucose metabolism in children
      with growth hormone deficiency].
AB  - OBJECTIVE: Numerous studies in children with growth hormone deficiency (GHD) show
      that recombinant human growth hormone (rhGH) treatment results in significant
      catch-up growth, but some papers reported that the children who underwent rhGH
      therapy might be at increased risk of diabetes. The aim of this study was to
      investigate the effects of rhGH treatment on blood glucose and insulin metabolism
      in children with GHD and the relationship between growth hormone (GH) and glucose
      homeostasis. METHODS: In this study, 44 children with GHD treated with rhGH [0.1
      U/(kgxd)] and age- and sex-matched 20 healthy children were enrolled. The GHD
      group included 28 males and 16 females aged from 4.5 to 16.5 years (mean 10.4 +/-
      2.6 years), including 18 cases of complete GHD and 26 cases of partial GHD. The
      sexual development stage of all subjects was in Tanner I. Oral glucose tolerance
      tests (OGTT) were done, and body mass index (BMI), serum insulin-like growth
      factor-1 (IGF-1) level and insulin resistance by homeostasis model (HOMA-IR) were
      measured at the time of diagnosis and every 3 months after rhGH therapy.
      Continuous glucose monitoring system (CGMS) was applied for two cases with
      hyperglycemia. RESULTS: (1) Fasting glucose and IGF-1 levels increased since 3
      months of treatment and did not decrease since then. The levels of fasting
      glucose and IGF-1 at every time points of rhGH therapy were higher than the
      levels at the time of diagnosis (F = 6.81, P < 0.01; F = 7.31, P < 0.01,
      respectively). HOMA-IR and fasting insulin levels were increased since 3 and 9
      months of treatment (P = 0.001 and P = 0.021, respectively). They decreased after
      12 months of therapy and the levels at 18 months of therapy were similar to that
      at diagnosis. (2) Pearson correlation analysis showed that HOMA-IR was positively
      correlated with BMI, IGF-1 and the duration of treatment (r = 0.251, 0.437,
      0.281, P < 0.01, respectively). The curve between HOMA-IR and duration of therapy
      was similar with parabola and the quadratic equation obtained was as follows:
      HOMA-IR = 1.5048 + 0.2177 x duration of therapy (months)-0.0103 x duration of
      therapy (months)(2) (r(2) = 0.147, F = 14.16, P < 0.01). (3) Two cases had
      transitory hyperglycemia. Their fasting glucose levels were all higher than 7.1
      mmol/L. The glucose levels returned to normal after 1 month and 5 days
      respectively. OGTT and CGMS showed that their plasma glucose levels were normal
      after rhGH therapy was applied again. CONCLUSION: The children who underwent rhGH
      therapy may be at increased risk of insulin resistance (especially during the
      first year) and the therapy may even induce transitory glucose metabolic disorder
      in a very small proportion of patients. Circulating IGF-1 may participate in the
      control of insulin sensitivity and play an important role in the hormonal balance
      between GH and insulin. It may be necessary to monitor glucose metabolism and IGF
      1 for all children who are treated with rhGH therapy.

PMID- 17217658
TI  - [Advances in diagnosis and treatment of Prader-Willi syndrome].

PMID- 17217659
TI  - [Glucagon-like peptide-1 based therapy for type 2 diabetes].

PMID- 17217660
TI  - [Attention deficit hyperactivity disorder and sleep disordered breathing in
      children].

PMID- 17217661
TI  - [Pathogenesis of respiratory syncytial virus infection].

PMID- 17217662
TI  - [Clinical application of wireless capsule endoscopy in pediatric and adolescent
      patients].
AB  - OBJECTIVE: Capsule endoscopy (CE) has been demonstrated to be safe and well
      tolerated in adults. However, its value in pediatric patients has not been well
      studied. The present study aimed to evaluate the safety and effectiveness of CE
      in pediatric patients with suspicious small bowel disorders. METHODS: Fifteen
      children and adolescents (less than 18 years) were referred to our study for
      suspected small bowel diseases from Aug. 2002 to May 2005. They aged from 3 to 18
      years. Among them, 5 patients were less than 10 years old. The range of weight
      was from 17 to 83 kg and height was from 49 to 176 cm. Clinical indications
      included obscure gastrointestinal bleeding (n = 12) and abdominal pain (n = 3).
      All the patients had normal results on upper and lower gastrointestinal
      examinations before they underwent CE. The procedures for capsule placement,
      gastric transit time, small bowel transit time, the average time of the
      elimination of the capsule, capsule findings, and complications were recorded.
      RESULTS: All the patients described that the capsule was easy to swallow except 3
      youngest children. Finally the capsule was delivered via gastroscopy with
      overtube for these three children under intravenous anesthesia. No capsule
      retention occurred during the study. Median recording time was (464 +/- 40) min.
      In 5 patients, the capsule did not pass the ileal valve by the end of the
      recording time. Median gastric transit time was (85 +/- 90) min. Median small
      bowel transit time was (283 +/- 106) min. The average time of the elimination of
      the capsule was (34.3 +/- 21.8) h. The detective yield of CE was 80%. These
      positive findings included Crohn's disease (5), hemangioma (2), angiodysplasia
      (2), Meckel diverticulum (1), polyp (1), and granulomatous lesions (1).
      CONCLUSION: CE was performed safely in pediatric patients after ingestion or
      endoscopic placement of the capsule. The high yield of abnormal findings was
      comparable to those of adult patients.

PMID- 17217663
TI  - [Detection of class I integron and its relation to antimicrobial resistance of
      Shigella flexneri in children].
AB  - OBJECTIVE: To investigate class I integron of Shigella flexneri, its prevalence
      in children, and its relation to bacterial resistance to antimicrobial agents.
      METHODS: Totally 51 strains of Shigella flexneri were isolated from fecal samples
      of children suffering from bacterial diarrhea seen between June 2004 and November
      2004 at Children's Hospital of Fudan University. Polymerase chain reaction (PCR)
      was employed to amplify various integron markers, including intI1, gene cassette
      region and 3' conserved region of class I intrgron; susceptibility of Shigella
      flexneri strains to 7 antimicrobial agents was determined by K-B (Kriby-Bauer)
      method. RESULTS: Forty-six strains of Shigella flexneri had intI gene with a
      positive rate of 90.2% (46/51); 24 strains of Shigella flexneri were positive for
      qacEDelta1-sul1, the positive rate was 47.1% (24/51); proportion of the isolates
      positive for all the three regions of class I integron was 43.1% (22/51); 46
      strains of intI positive Shigella flexneri were all positive for ant (3'')-I.
      Among 46 strains of intI positive isolates, proportions of the isolates positive
      and negative for qacEDelta1-sul1 were 47.8% (22/46) and 52.2% (24/46),
      respectively. In the class I integron positive Shigella flexneri, the resistance
      rates of ampicillin (chi(2) = 10.13, P < 0.01) and chloramphenicol (chi(2) =
      19.97, P < 0.01) were significantly higher than those in the class I integron
      negative group. CONCLUSIONS: Class I integron was detected in 90.2% of Shigella
      flexneri in children; carriage of class I integron is related to antimicrobial
      resistance of Shigella flexneri.

PMID- 17217664
TI  - [Effects of feeding intervention on development of eczema in atopy high-risk
      infants: an 18-month follow-up study].
AB  - OBJECTIVE: To assess the preventive effects of different dietary regimens on
      development of eczema and food allergy in infants at high-risk for allergy.
      METHODS: Forty-six infants whose parents were atopic and umbilical cord IgE >
      0.35 kU/L were enrolled in the study. The infants were randomly assigned at birth
      to one of 2 dietary regimen protocols: those in intervention group (23 cases)
      were breast fed till more than 4 months of age, then followed by feeding with
      partially hydrolyzed formula (pHF), combined solid foods avoidance until 4-month
      of age, egg, fish, shrimp avoidance until 12-month of age. The other 23 cases in
      non-intervention group were breast fed for less than 4 months, or bottle fed with
      cow's milk-based formula, egg yolk was introduced at 4-month of age, and egg
      white at 6-month of age, besides, no any other dietary avoidance was applied. All
      the infants were followed-up for 18 months. The primary end point was the
      presence of atopic eczema. Food allergy was detected by fresh food prick-to-prick
      tests or in vitro sIgE or Fx5E. RESULTS: At 6 months, 12 months and 18 months,
      the incidence of eczema in intervention group was 4.3% (1/23), 8.7% (2/23), and
      17.4% (4/23), respectively, which was significantly reduced as compared to that
      of the non-intervention group, which was 26.1% (6/23), 34.8% (8/23), and 39.1%
      (9/23), respectively. Food allergy was found in 13.0% (3/23) of intervention
      group and 34.8% (9/23) of non-intervention group by skin prick tests or sIgE. Egg
      white was the most common offending food. CONCLUSION: Early life dietary
      interventions which included breastfeeding, delayed solid food introducing, pHF
      feeding, and high risk food avoidance could reduce the risk of atopic eczema and
      food allergy development, and was probably an effective primary intervention
      method for infants at high risk for atopy.

PMID- 17217665
TI  - [Correlation between psychopathological symptoms, coping style in adolescent and
      childhood repeated physical, emotional maltreatment].
AB  - OBJECTIVE: To study possible relationship between psychopathological symptoms,
      positive and negative coping styles in adolescents who experienced repeated
      serious childhood physical abuse (CPA), moderate CPA, and childhood emotional
      abuse (CEA). METHODS: A total of 5453 students were recruited as subjects from 9
      middle schools at grades 7, 8, 10, and 11. They provided informed consent and
      participated in the self-administered anonymous survey on their frequencies of
      serious or moderate physical abuse and emotional abuse by his/her parents or
      other caregivers about average times of experiencing maltreatment every year
      during primary school. The Symptoms Checklist 90 (SCL-90) was used to rate
      general mental problem and 9 special psychopathological symptoms. The trait
      positive and negative coping styles were assessed with the Trait Coping Style
      Questionnaire (TCSQ). Totally 5141 respondents substantially completed surveys.
      It was defined as repeating childhood maltreatment that the adolescent reported
      he/she had suffered 3 or more episodes of one or more forms of serious CPA,
      moderate CPA, and CEA. Multinomial logistic regression model was used to analyze
      the effect of the types and quantities of repeating childhood experiences on
      mental health when the positive, negative coping styles, and both of them entered
      the statistics model, taking the demographic variables as covariates. RESULTS: Of
      respondents, 9.1 percent were rated as having general mental health problem. The
      rates of somatization, obsession, interpersonal susceptivity, depression,
      anxiety, phobia, paranoia, and psychotic symptoms were 1.3%, 3.6%, 3.6%, 2.8%,
      2.2%, 4.0%, 2.1%, 2.8% and 1.6%, respectively. Dose-response trend existed
      between the number of items of repeating serious CPA, moderate CPA, CEA, and
      rates of general mental problems, 9 kinds of psychopathological symptoms, number
      of positive items of psychopathological symptoms. Compared with the respondents
      without serious CPA, moderate CPA or CEA, those with repeating childhood
      maltreatment had higher scores of negative coping styles. In the respondents with
      repeating childhood maltreatments, the prevalence of general mental problems and
      number of positive psychopathological symptoms increased with the rising of
      scores of negative coping styles. The results from multinomial logistic
      regression analysis showed that negative coping style decreased the odds ratio
      (OR) of repeating serious CPA, moderate CPA, and CEA with general mental health
      problems, but positive coping style did not. CONCLUSIONS: The experiences of
      repeating childhood physical or emotional maltreatment are associated with a wide
      variety of psychopathological symptoms and general mental health problems.
      Negative coping strategies may moderate the links of childhood abusive
      experiences and mental problems.

PMID- 17217666
TI  - [Clinical characteristics of Candida septicemia seen in a neonatal intensive care
      unit: analysis of 9 cases].
AB  - OBJECTIVE: To analyze the clinical characteristics of Candida septicemia occurred
      in neonatal intensive care unit (NICU). METHODS: The clinical characteristics of
      9 confirmed cases with septicemia caused by Candida species yeasts were analyzed
      and summarized. RESULTS: All the 9 cases were preterm infants, including 6 cases
      of very low birth weight infants. All these cases were treated with broad
      spectrum antibiotics and parenteral nutrition before fungal infections occurred.
      Eight cases had percutaneous inserted central catheter (PICC). Three cases had
      been on ventilator. The symptoms of fungal infection were presented at 8 to 22
      days of age. Apnea, poor perfusion and lethargy were common symptoms of these
      cases with fungal infection. Seven of the 9 cases developed thrombocytopenia. C
      reactive protein was elevated in 7 cases. Blood culture showed C. albicans in 1
      case, C. parapsilosis in 2 cases, and C. guilliermondii in 6 cases. In 5 cases
      PICC culture showed the same fungus as blood culture revealed at the same time.
      All the 9 patients received antifungal therapy. Six patients were cured, two died
      and in one patient the treatments were given up by the parents. CONCLUSIONS: The
      high risk factors of Candida septicemia in newborn infants include preterm, PICC,
      broad-spectrum antibiotic therapy and mechanical ventilation. The clinical
      presentations are always nonspecific. Thrombocytopenia and elevated C reactive
      protein are common in Candida septicemia patients. Early-started antifungal
      therapy can improve the prognosis.

PMID- 17217667
TI  - [A report of 4 cases with tracheal bronchus].

PMID- 17217668
TI  - [Bronchiolar disorders in 6 children: clinico-radiologic findings, diagnosis, and
      treatment].

PMID- 17217669
TI  - [Expression of intestinal trefoil factor and its clinical significance in
      gastrointestinal functional failure in critically ill children].

PMID- 17217670
TI  - [A case of beta-ketothiolase deficiency].

PMID- 17217671
TI  - [Report of a case with branchio-oto-renal syndrome].

PMID- 17217672
TI  - [Sinus histiocytosis with giant lymphadenopathy in a case].

PMID- 17217673
TI  - [Headache, vomiting, reduced hearing and papilloedema].

PMID- 17217674
TI  - [Chinese guidelines for the use of nutritional support in critically ill
      neonates].

PMID- 17217675
TI  - [Nutrition Safari for Innovative Solutions: 18th International Congress of
      Nutrition].

PMID- 17217676
TI  - [Requirements for English abstract of pediatric original articles (IX)].

PMID- 17217677
TI  - [The proper time for initiating beta-blockers in treatment of chronic heart
      failure].

PMID- 17217678
TI  - [The use of ACE inhibitors in treatment of chronic heart failure should still be
      emphasised].

PMID- 17217679
TI  - [The important role of angiotensin receptor blocker on treatment of chronic heart
      failure].

PMID- 17217680
TI  - [Treatment of chronic heart failure with statins: potential advantages and
      disadvantages].

PMID- 17217681
TI  - [Beta1-adrenergic receptor (Arg389Gly) polymorphism and response to bisoprolol in
      patients with chronic heart failure].
AB  - OBJECTIVE: The purpose of this study was to investigate the relation between the
      Arg389Gly polymorphism of the beta(1)-AR gene and chronic heart failure (CHF) and
      to evaluate the effect of this polymorphism on clinical response to beta
      adrenoceptor blockade (bisoprolol) in patients with CHF. METHODS: One hundred and
      ten patients with stable CHF receiving basic therapy for heart failure were
      included. Before initiation and 3 months after the maximal tolerated dose of
      bisoprolol was reached, all indices (including BP, HR, LAD, LVEDD, LVESD, LVEF,
      BNP level, 6 min walk distance) were measured and compared with the Arg389Gly
      genotypes, which identified by PCR-restriction fragment length polymorphism
      analysis. We also determined the Arg389Gly genotypes in 100 healthy control
      subjects, and compared the distribution of Arg389Gly genotypes with that in CHF.
      RESULTS: No difference was observed between the two groups in any of the three
      genotypes (CC, CG and GG). The prevalences of the three genotypes in normal
      subjects and patients with CHF were Arg389Arg 0.53 vs. 0.51, Arg389Gly 0.40 vs.
      0.40, Gly38Gly 0.07 vs. 0.09, respectively. After 3 months of bisoprolol usage, a
      significant improvement in LVEF was observed in CC group, which increased from
      (36.7 +/- 8.63)% to (44.1 +/- 9.53)%, CG group, from (35.76 +/- 8.39)% to (42.90
      +/- 9.41)%, but not GG group, from (36.00 +/- 5.66)% to (37.33 +/- 5.64)%. The
      improvement in BNP was also observed in CC [from (502.93 +/- 160.80) ng/L to
      (325.26 +/- 135.63) ng/L], CG [from (525.76 +/- 157.66) ng/L to (331.79 +/-
      133.97) ng/L], but not GG [from (505.33 +/- 125.07) ng/L to (429.67 +/- 182.39)
      ng/L]. Arg389-homozygous patients showed a substantially greater improvement in
      LVEF and BNP, compared with Gly389-homozygous patients (all P < 0.01).
      CONCLUSIONS: There was no difference in the prevalence of the three genotypes
      between healthy and CHF subjects. The Gly389 polymorphism of the beta(1)-AR gene
      was not associated with an increased risk of CHF. The Arg389 variant of the
      beta(1)-AR gene was associated with a greater response to bisoprolol than that of
      the Gly389 variant in patients with CHF.

PMID- 17217682
TI  - [Correlation of hyponatremia with plasma renin activity, antidiuretic hormone and
      brain natriuretic peptide in chronic heart failure].
AB  - OBJECTIVE: To observe the changes of plasma renin activity, antidiuretic hormone
      and brain natriuretic peptide in chronic heart failure (CHF) and their
      correlation with hyponatremia. METHODS: Plasma levels of PRA, ADH, and BNP were
      measured by radioimmunology in 76 CHF patients. Forty-one out of 76 CHF patients
      with hyponatremia and 35 CHF patients without hyponatremia were identified by
      serum sodium. The rates of rehospitalization within 3 months were compared in two
      groups. RESULTS: Levels of plasma renin activity, ALD, and BNP in CHF patients
      with hyponatremia were notably higher than those in patients without hyponatremia
      classified by New York Heart Association (NYHA) grade II - IV: PRA [(2.7 +/- 1.0)
      ng.ml(-1).h(-1) vs. (1.8 +/- 0.7) ng.ml(-1).h(-1), (4.3 +/- 1.2) ng.ml(-1).h(-1)
      vs. (3.0 +/- 0.9) ng.ml(-1).h(-1), (5.6 +/- 1.3) ng.ml(-1).h(-1) vs. (3.5 +/-
      1.1) ng.ml(-1).h(-1), respectively, P < 0.05], ADH [(59.7 +/- 17.4) ng/L vs.
      (48.6 +/- 15.3) ng/L, (68.4 +/- 17.6) ng/L vs. (56.3 +/- 19.2) ng/L, (75.3 +/-
      20.0) ng/L vs. (51.4 +/- 16.2) ng/L, respectively, P < 0.05] and BNP [(276.4 +/-
      75.2) ng/L vs. (185.3 +/- 55.3) ng/L, (380.1 +/- 113.6) ng/L vs. (258.5 +/- 62.1)
      ng/L, (564.0 +/- 125.2) ng/L vs. (405.3 +/- 102.9) ng/L, respectively, P < 0.05].
      In the simple regression analyses, hyponatremia was negative correlated with PRA,
      ADH and BNP (r = -0.31, P < 0.05; r = -0.28, P < 0.05, r = -0.80, P < 0.01). The
      rate of rehospitalization within 3 months in hyponatremia group was higher than
      that in control group. CONCLUSIONS: There is relation of hyponatremia to the
      changes of plasma renin activity, antidiuretic hormone and brain natriuretic
      peptide in chronic heart failure. Hyponatremia may accelerate the excretion of
      plasma PRA, ADH and BNP in chronic heart failure. Neuroendocrine activation in
      patients of congestive heart failure with hyponatremia is higher than that of
      normal natremia group.

PMID- 17217683
TI  - [Bone marrow mesenchymal cell transplantation reduces left ventricular remodeling
      in heart failure following acute myocardial infarction].
AB  - OBJECTIVE: Bone marrow mesenchymal cell (MSC) transplantation has been shown to
      improve heart failure but the mechanism and the subsequent effects are unclear.
      We tested the hypothesis that MSC transplantation reduces left ventricular
      remodeling through the MMP/TIMP system in heart failure following acute
      myocardial infarction. METHODS: Female SD rats underwent coronary artery ligation
      to induce myocardial infarction. Four weeks later, the rats were divided into the
      test group (n = 7) and the control group (n = 7), respectively. The donor MSCs
      were harvested and expanded from male SD rats (5 x 10(6) in 50 microl PBS) and
      injected into the ischemic myocardium, while the control group received the same
      volume of PBS. Left ventricular morphology was then evaluated in both groups
      through staining with H&E and Masson's trichrome. Immunohistochemical staining
      was used to examine the expressions of MMP2 and TIMP1, as well as type I and type
      III collagens, in the scar zones. The protein levels of MMP2 and TIMP1 were
      determined by Western blotting. RESULTS: MSC differentiated into fibroblast-like
      cells at 21 days after transplantation in the test group. In addition, many
      inflammatory cells infiltrated and aggregated in the scar area, but this effect
      was reduced at day 7 after transplantation. The following changes were noted in
      the test group compared to the control group: ejection fraction and shortening
      fraction were higher [(63.43 +/- 3.97)% vs. (36.20 +/- 3.99)%, (31.71 +/- 1.98)%
      vs. (18.00 +/- 2.07)%, P < 0.05]; dp/dt(min) was reduced [(-4756.24 +/- 270.00)
      mm Hg/s vs. -2789.53 +/- 624.13) mm Hg/s, P < 0.05]; the left ventricular
      thinning ratio was significantly higher [(76.34 +/- 2.66)% vs. (64.37 +/- 2.36)%,
      P < 0.05]; the infarct size was smaller [(36.19 +/- 0.83)% vs. (42.12 +/- 1.88)%,
      P < 0.05]; type I collagen expression in the scar area was much higher; type III
      collagen expression was much lower; MMP2 expression was reduced and TIMP1
      expression was increased. CONCLUSION: MSC transplantation led to dynamic changes
      in the collagen network through regulation of MMP2/TIMP1 system and consequently
      interrupted the progress of adverse LV remodeling in heart failure following
      acute myocardial infarction.

PMID- 17217684
TI  - [Abnormal abundances of calcium cycling regulatory proteins in rabbit myocytes
      with heart failure].
AB  - OBJECTIVE: To investigate the abnormal abundances of calcium regulatory proteins
      in rabbit myocytes with failing hearts. METHODS: Sixteen rabbits were divided
      into two groups: 8 rabbits with heart failure induced by volume plus pressure
      overload and 8 sham-operated animals. The hemodynamic parameters and cardiac
      structure and function were detected via catheterization and echocardiography
      respectively. L-type calcium channel (LTCC), Ryanodine receptor 2 (RyR2),
      Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a), and Na(+)-Ca(2+) exchanger (NCX)
      protein abundances were determined by Western blot analysis. RESULTS: The ratio
      of left ventricular mass to body weight, heart rate and left ventricular end
      diastolic pressure in heart failure rabbits were significantly increased compared
      with sham-operated rabbits (P < 0.01), but their left ventricular shorten
      fraction [(21.3 +/- 4.00)% vs. (36.5 +/- 1.36)%] and ejection fraction (0.45 +/-
      0.07 vs. 0.70 +/- 0.02) were decreased (P < 0.01). In heart failure rabbits, the
      abundances of LTCC and RyR2 were significantly decreased (R(LTCC/actin): 0.287 +/
      0.029 vs. 0.624 +/- 0.009; R(RyR2/actin): 0.106 +/- 0.001 vs. 0.203 +/- 0.011; P
      < 0.01), whereas the expressions of SERCA2a and NCX were markedly increased
      (R(NCX/actin): 0.497 +/- 0.015 vs. 0.221 +/- 0.014; R(SERCA2a/actin): 0.611 +/-
      0.036 vs. 0.433 +/- 0.008; P < 0.01). CONCLUSIONS: Reductions of LTCC and RyR2
      might contribute to risk factors of systolic dysfunction in failing hearts. In
      early stage of heart failure, upregulated SERCA2a and NCX protein levels may be
      helpful for maintaining cardiac performance.

PMID- 17217685
TI  - [Effect of losartan on sarcoplasmic reticulum Ca2+ handing proteins in heart
      failure rabbit].
AB  - OBJECTIVE: To investigate the effects of losartan on mRNA expression of
      myocardial sarcoplasmic reticulum calcium handling proteins (SERCA2, RyR2 and
      PLB) and the role of which in prevention of chronic heart failure in rabbit.
      METHODS: After chronic heart failure was induced by ligation of the left anterior
      descending artery in rabbits, the animals were treated with losartan. At 8 weeks
      after ligation, left ventricular function, hemodynamic parameters, and SERCA2,
      RyR2, PLB mRNA expressions were observed. RESULTS: Compared with the control
      group (group C), LVEDP in the infarcted group (group I) increased (P < 0.01),
      while +dp/dt(max) and -dp/dt(max) decreased significantly (P < 0.01). LVEDP was
      lower but +dp/dt(max) and -dp/dt(max) significantly higher in the losartan
      treated group (group L) than those in group I (P < 0.05). SERCA2, RyR2, and PLB
      mRNA expressions in group I were remarkably lower than those in group L (P <
      0.01) and group C (P < 0.01), respectively. CONCLUSION: Losartan can improve
      cardiac function, probably owing to its upregulating mRNA expressions of
      myocardial sarcoplasmic reticulum Ca(2+) handling proteins (RyR2, SERCA2 and PLB)
      in the prevention of heart failure.

PMID- 17217686
TI  - [Observation of functional remodeling of Ca2+-activated Cl- channel in pacing
      induced canine failing heart].
AB  - OBJECTIVE: To study whether Ca(2+)-activated Cl(-) current (I(to2)) contributes
      to the functional remodeling of the failing heart. METHODS: The cardiac myocytes
      were isolated enzymatically from rapidly pacing-induced failing canine hearts
      (HF) at room temperature. Patch-Clamp whole cell recording technique was employed
      to record the I(to2). The Cl(-) transport blocker 4, 4'-diisothiocyanostilbene-2,
      2'-disulfonic acid (DIDS, 200 micromol) was used to isolated the I(to2). The
      relations of I(to2) to L-type Ca(2+) current (I(Ca-L)) and to the membrane
      voltage under the constant intracellular [Ca(2+)]i were evaluated in HF and the
      normal hearts. RESULTS: We found that the current density of I(to2) was
      significantly decreased in HF cells compared with the controls. At membrane
      voltage of 20 mV, for example, the I(to2) density was (3.02 +/- 0.54) pA/pF in
      control cells (n = 7) vs. (1.31 +/- 0.25) pA/pF in HF (n = 8) cells, P < 0.05.
      While the averaged I(Ca-L) density did not show difference between two groups.
      The time constant of current decay of I(to2) was similar in both types of cells.
      However, in intracellular Ca(2+) clamped mode with 100 micromol [Ca(2+)]i, I(to2)
      density was increased significantly in HF cells at membrane voltage of +30 mV or
      higher. CONCLUSIONS: Our results suggest that the decrease of I(to2) density may
      contribute to the prolongation of the action potential in failing heart. I(to2)
      density abnormality may cause cardiac arrhythmia and a delayed after
      depolarization. Impaired Ca(2+) handing in HF cells rather than reduced CLCA
      function itself may result in this abnormality.

PMID- 17217688
TI  - [Association of paraoxonase polymorphisms and serum homocysteine thiolactone
      complex with coronary heart disease].
AB  - OBJECTIVE: To investigate the relationship between paraoxonase (PON)
      polymorphisms and serum homocysteine thiolactone (HTL) and coronary heart
      diseases. METHOD: In this prospective study, serum complex of HTL levels using
      ELISA, and the lever of serum Hcy using high pressure liquid chromatography
      (HPLC), determined the PON1/T(-107)C and PON2/C311S genotypes using PCR
      restriction fragment length polymorphisms 203 were measured in patients with
      angiographic documented coronary heart disease (CAD) and 117 controls. RESULTS:
      Serum levels of Hcy and the complex of HTL in CAD patients were significantly
      higher than that in controls (P < 0.05). No significant difference was found in
      frequencies of PON1/T(-107)C genotypes and alleles (P > 0.05) between CAD patient
      and controls. The PON2/C311S (SS) genotype was lower in CAD patients than that in
      controls (P < 0.05), while the frequency of allele was similar between the two
      groups (P > 0.05). The T allele of PON1/T(-107)C and S alleles of PON2/C311S
      polymorphism were associated with lower plasma Hcy and HTL complex [Hcy (11.83 +/
      4.76) micromol/L vs (15.32 +/- 10.32) micromol/L, P < 0.05; HTL complex (24.36
      +/- 9.30) U/ml vs (32.05 +/- 10.44) U/ml, P < 0.05]. The genetype PON2 and allele
      C were higher in CAD patients with type 2 diabetes than that in CAD patients
      without type 2 diabetes and controls (P < 0.005). CONCLUSIONS: The elevation of
      serum Hcy and the complex of HTL were associated with increased risk of coronary
      heart disease. The allele PON1/(-107)T and PON2/311S might be protective for the
      development of atherosclerosis.

PMID- 17217689
TI  - [Serum high-sensitivity C-reaction protein and heart fatty acid binding protein
      level and cardiac accidents in patients with unstable angina pectoris].
AB  - OBJECTIVE: To investigate the relationship between serum high-sensitivity C
      reaction protein (hs-CRP) and heart fatty acid binding protein (h-FABP) on
      cardiac accidents in patients with unstable angina pectoris (UAP). METHOD: Serum
      levels of hs-CRP, h-FABP, cardiac troponin-I (cTn-I) and creatine kinase MB
      isoenzyme (CK-MB) were measured and cardiac accidents within 2 weeks after the
      test were observed in 74 patients (male 45) with stable AP (SAP) and 56 patients
      (male 29) with UAP. RESULTS: The incidence of cardiac accidents was significantly
      higher in UAP group (26.8%) than that in SAP group (10.53%, P < 0.001). Serum hs
      CRP [(7.64 +/- 2.18) mg/L vs. (1.78 +/- 0.62) mg/L, P < 0.001], h-FABP [(16.46 +/
      5.28) microg/L vs. (3.15 +/- 2.61) microg/L, P < 0.001] and cTn-I [(1.28 +/-
      0.43) microg/L vs. (0.67 +/- 0.09) microg/L, P < 0.001] levels were also
      significantly higher in UAP group than those in SAP group. The serum hs-CRP and h
      FABP levels for patients with cardiac accidents in the SAP group were (6.32 +/-
      2.06) microg/L and (8.76 +/- 3.83) microg/L respectively, which were higher than
      those for the patients having no cardiac accidents in the control (P < 0.01). The
      serum hs-CRP, h-FABP, cTn-I and CK-MB levels in patients with cardiac accidents
      were significantly higher than those in patients without cardiac accidents in
      both SAP and UAP groups. CONCLUSION: Measuring traditional parameters for
      myocardial damage (cTn-I and CK-MB) in combination with hs-CRP and h-FABP is
      valuable for predicting the risk of recent cardiac accidents for AP patients.

PMID- 17217690
TI  - [Elevated serum secretory type II phospholipase A2 in patients with coronary
      heart disease].
AB  - OBJECTIVE: To measure the serum level of secretory type II phospholipase A2
      (sPLA2) in patients with coronary heart disease and investigate the possible
      relationship with IL-8 and LPA. METHODS: A total of 110 patients with acute
      coronary syndrome (ACS), 63 patients with stable coronary heart disease (SCHD)
      group and 89 non-CHD control patients were studied. Serum levels of sPLA2, IL-8,
      LPA and hs-CRP were measured and the correlation among these parameters was
      observed. RESULTS: The levels of serum sPLA2 [(68 +/- 17) U/ml], IL-8 [(182 +/-
      80) pg/ml] and LPA [(2.85 +/- 0.36) micromol/L] were significantly higher in CHD
      patients than those in controls [sPLA2: (55 +/- 12) U/ml; IL-8: (119 +/- 33)
      pg/ml; LPA: (2.34 +/- 0.36) micromol/L, all P < 0.01], and sPLA2 and IL-8 were
      also significantly higher in ACS patients [sPLA2: (71 +/- 18) U/ml; IL-8: (195 +/
      78) pg/ml] than those in SCHD patients [sPLA2: (63 +/- 12) U/ml; IL-8: (159 +/-
      79) pg/ml, both P < 0.01]. Serum sPLA2 level was positively correlated with hs
      CRP, IL-8 and LPA (r = 0.203, P = 0.007; r = 0.658, P < 0.01; r = 0.231, P =
      0.005, respectively). The relative risk of having CHD is 6.248 (P < 0.01) with
      the sPLA2 level above 63.75 U/ml. CONCLUSION: Elevated serum sPLA2 level is a
      risk factor for CHD.

PMID- 17217691
TI  - [Relationship between right ventricular mechanical delay and right ventricular
      systolic function in patients with pulmonary hypertension].
AB  - OBJECTIVE: To investigate the relationship between right ventricular (RV)
      mechanical delay and RV dysfunction in patients with pulmonary hypertension (PH).
      METHODS: A total of 51 patients with PH were divided into mild, moderate and high
      PH groups and 30 healthy volunteers served as control group. RV mechanical delay
      (defined as the difference in time to peak systolic annular velocity between the
      RV free wall and the ventricular septum) and RV fractional area change were
      obtained on apical four chamber view with Quantitive Tissue Velocity Imaging
      (QTVI). RESULTS: RV mechanical delay increases in proportion to pulmonary
      pressure. RV fractional area change was similar between control and mild PH
      patients while significantly reduced in moderate and high PH patients compared to
      controls. RV mechanical delay significantly correlated to RV fractional area
      change in all PH groups (r = -0.79; r = -0.66; r = -0.80, all P < 0.05).
      CONCLUSION: RV mechanical delay measured by QTVI can be used to evaluate RV
      dysfunction in patients with pulmonary hypertension.

PMID- 17217692
TI  - [The clinicopathological endomyocardial biopsy analysis in cardiac transplant
      recipients due to end-stage heart failure].
AB  - OBJECTIVE: Endomyocardial biopsies from 42 (35 males and 7 females, aged 43.3
      years) heart transplant recipients due to end-stage heart failure between June
      2004 and January 2006 in our institute were obtained for pathological studies.
      METHODS: Sixteen patients underwent 1 endomyocardial biopsy (right ventricular
      septum) between 13 days to 5 months, 13 patients underwent second biopsy between
      1.5 to 8 months and 10 patients underwent third biopsy between 3 to 8.5 months
      post transplantation. Specimen were stained by hematoxylin-eosin (HE) and
      Phosphotungstic Acid Hematoxylin (PTAH) and observed under light microscope and
      cardiac allograft rejection were evaluated according to the Revision of the 1990
      working formulation for the standardization of nomenclature in the diagnosis of
      heart rejection in 2004. RESULTS: The rejection grades were as follows: Grade 0 R
      in 31 biopsies; Grade 1 R (mild rejection 1990 grade 1A, 1B and 2.) in 30
      biopsies; Grade 2 R (moderate rejection, 1990 grade 3A) in 3 biopsies; Grade 1 R
      cellular rejection companies with humoral rejection in 1 biopsy. Cellular
      rejection with Quilty effect was found in 2 biopsies. Ischemic myocardial injury
      presented in 4 biopsies. Quilty effect was observed in 1 biopsy. Cytomegalovirus
      or toxoplasmic myocarditis was not observed. CONCLUSIONS: Endomyocardial biopsy
      (EMB) is a valuable diagnostic procedure for rejection surveillance in heart
      allograft recipients. The observed low rejection incidence and mild rejection
      from specimens of our heart recipients were comparable to the results of
      developed countries.

PMID- 17217693
TI  - [Outcome of fatal pulmonary embolism post coronary intervention].
AB  - OBJECTIVE: To study the occurrence, management and prognosis of fatal pulmonary
      embolism in patients underwent coronary intervention in our department. METHOD:
      Seven patients had fatal pulmonary embolism after coronary intervention in six
      years, we analysis each patient by the occurrence, prognosis, management of the
      disease. RESULTS: During the last 6 years, 7 [five males, mean age (55.9 +/-
      11.7) years, 5 after coronary angiography and 2 after percutaneous coronary
      intervention] patients developed fatal pulmonary embolism after PCI. All 7
      patients presented respiratory and cardiac arrest within 24 hours post coronary
      intervention. Three patients died, one patient experienced brain death and
      another three patients survived and are alive without complication till now.
      CONCLUSION: The fatal pulmonary embolism is a scarce complication after coronary
      intervention with high acute mortality and satisfactory outcome for survivors.

PMID- 17217694
TI  - [The effects of antiarrhythmic peptide AAP10 on ventricular arrhythmias in
      rabbits with healed myocardial infarction].
AB  - OBJECTIVE: To evaluate the effects of antiarrhythmic peptide (AAP10) on
      ventricular arrhythmias in rabbits with healed myocardial infarction (OMI).
      METHODS: Thirty rabbits were randomly divided into three groups (n = 10 each):
      Sham group, left thoracotomy was performed without coronary ligation; OMI group
      and OMI + AAP10 group, the circumflex coronaries were ligated. Three months post
      operation, the electrophysiological and antiarrhythmic effects of AAP10 were
      assessed in the arterially perfused rabbit left ventricular wedge preparation.
      Sham and OMI group were perfused with Tyrode's solution and OMI + AAP10 group was
      perfused with Tyrode's solution + AAP10 (80 nmol/L). Transmembrane action
      potentials were recorded simultaneously from endocardium and epicardium together
      with a transmural ECG by use of 2 separate intracellular floating
      microelectrodes. The stimulus-response-interval (SRI) of the epicardium and the
      incidence of ventricular tachycardia (VT) were observed. Whole heart and left
      ventricular weights, the left ventricular thickness at infarct border zone were
      measured. RESULTS: Whole heart and left ventricular weights as well as the left
      ventricular thickness at the infarct border zone significantly increased post
      infarction. VT was induced in 8 out of 10 rabbits in OMI group and in 2 out of 10
      rabbits in OMI + AAP10 group (P < 0.05). SRI was also significantly shortened in
      OMI + AAP10 group compared to OMI group [SRI-1: (20.59 +/- 0.79) ms vs. (28.71 +/
      0.55) ms; SRI-2: (30.42 +/- 0.74) ms vs. (38.67 +/- 0.49) ms, all P < 0.01].
      However, the action potential morphology and duration were similar between OMI
      and OMI + AAP10 groups. CONCLUSION: The antiarrhythmic peptide (AAP10) can
      increase gap junctional intercellular conductance without affecting the action
      potential morphology and duration and decrease the incidence of inducible
      ventricular tachycardia.

PMID- 17217695
TI  - [Histopathological changes post cryoablation in canine myocardium].
AB  - OBJECTIVE: The purpose of this study was to observe histopathological changes
      post cryoablation in canine myocardium, to characterize the specific ablation
      lesion post cryoablation. METHODS: Cryothermal ablation was applied on myocardium
      (both epicardium and endocardium) of 14 mongrel dogs with different ablation
      parameters (-25 degrees C x 4 min, -50 degrees C x 4 min, -75 degrees C x 4 min, 
      75 degrees C x 2 min, -75 degrees C x 6 min, -75 degrees C x 8 min). Lesion
      dimensions and histopathologic changes were observed. RESULTS: The discrete,
      sharply delimited lesions were detected in cryoablated myocardium.
      Histologically, cryoablation in all temperatures studied induced heterogeneous
      necrosis of the myocardium. Lesion dimensions are related to freezing time and
      temperature. CONCLUSION: Cryoablation is a feasible and preferably choice for
      clinical application due to its controllable myocardium lesions.

PMID- 17217696
TI  - [The role of cyclooxygenase on angiogenesis and endothelial progenitor cell
      mobilization in rat ischemic myocardium].
AB  - OBJECTIVE: To investigate the effect of COX1 and COX2 on angiogenesis and
      endothelial progenitor cell mobilization in rats with experimental myocardial
      infarction (MI). METHODS: The rats were randomly divided into 3 groups: MI group,
      MI plus rofecoxib group and MI plus valeryl salicylate group. At the 7th day
      after operation, circulating EPCs, plasma VEGF and HIF-1alpha mRNA of ischemic
      myocardium were measured. At the 28th day post operation, capillary densities
      were also measured in ischemic myocardium. RESULT: Compared with the MI group and
      the MI plus valeryl salicylate group, circulating EPCs, plasma VEGF, HIF-1alpha
      mRNA and capillary densities of ischemic myocardium were all decreased in MI plus
      rofecoxib group. CONCLUSION: The present study revealed that COX2 play an
      important role with angiogenesis and endothelial progenitor cell mobilization in
      rat with experimental MI by modulating expression of VEGF and HIF-1alpha.

PMID- 17217697
TI  - [The effect of telomerase reverse transcriptase on 5-HT induced pulmonary artery
      smooth muscle cells proliferation].
AB  - OBJECTIVE: To investigate the effect of telomerase reverse transcriptase (TERT)
      to the proliferation of 5-HT induced pulmonary artery smooth muscle cells
      (PASMCs). METHODS: The PASMCs proliferation experiment was performed to detect
      the effort on PASMCs of 5-HT or ASODN TERT (antisense oligoribonucleotides TERT
      designed according to the rat TERT mRNA sequence of gene bank). The
      immunohistochemistry staining experiment and the in situ hybridization experiment
      were to detect the TERT protein and mRNA expression with 5-HT or ASODN TERT. FITC
      marked ASODN TERT experiment was done to research the distribution of ASODN TERT
      in PASMCs. RESULTS: 5-HT promoted PASMCs proliferation in a dose-dependent manner
      (10(-9) - 10(-5) mol/L). 5-HT also significantly increased TERT expression at
      protein and mRNA levels as shown by immunohistochemistry staining and the in situ
      hybridization studies. This effect could be blocked by ASODN TERT in a time and
      dose-dependent manner. CONCLUSIONS: Our experiments show TERT is one of the key
      factors in the procession of 5-HT induced PASMCs proliferation. ASODN TERT might
      be a potential therapy agent for pulmonary hypertension.

PMID- 17217698
TI  - [Role of AcSDKP on collagen synthesis and degradation in cultured rat cardiac
      fibroblast].
AB  - OBJECTIVE: To investigate the role of AcSDKP on collagen synthesis and
      degradation in cultured rat cardiac fibroblasts. METHODS: Neonatal rat cardiac
      fibroblasts were isolated and stimulated by PDGF. The cell proliferation was
      observed by (3)H-TdR incorporation assay. The synthesis of collagen was measured
      by (3)H-proline incorporation assay. The expression of type I and type III
      collagen and MMP-1 protein were measured by Western blot. The MMP-2 and MMP-9
      activity was evaluated with zymography assay. RESULTS: PDGF stimulated cardiac
      fibroblasts proliferation with increased collagen synthesis and type I and type
      III collagen protein expressions as well as MMP-2 and MMP-9 activities and MMP-1
      expression. AcSDKP inhibited cardiac fibroblasts proliferation induced by PDGF
      and reduced collagen synthesis and type I and type III collagen protein
      expression. AcSDKP also further up-regulated MMP-2 and MMP-9 activities and MMP-1
      expression in cardiac fibroblasts induced by PDGF. CONCLUSION: AcSDKP inhibited
      proliferation and collagen synthesis and up-regulated matrix metalloproteinases
      activity or expression induced by PDGF, which was possibly related with the
      effect of AcSDKP anti-fibrosis.

PMID- 17217704
TI  - [Recent progress in short QT syndrome].

PMID- 17217707
TI  - [New concepts in searching for primary aldosteronism in hypertension: advances in
      screening, confirming and subtyping tests].

PMID- 17217708
TI  - [Aldosterone-to-renin ratio threshold for screening primary aldosteronism in
      Chinese hypertensive patients].
AB  - OBJECTIVE: In recent years, the assessment of the plasma aldosterone-to-renin
      ratio (ARR) has become a most effectively and commonly used method for screening
      primary aldosteronism from hypertensive patients. It is known that there is a
      large variance in ARR value between races and ARR is affected by many factors,
      such as drugs, posture and serum potassium etc. The objective of this study is to
      establish the threshold of ARR for screening primary aldosteronism in Chinese
      hypertensive patients. METHODS: A total of 110 hypertensive patients were
      recruited and divided into essential hypertension group (n=65) and
      adenoma/hyperplasia group (n=45) according to the adrenal contrast CT scan.
      Antihypertensive drugs which can affect ARR such as beta-blockers,
      dihydropyridine calcium channel blockers (CCBs), ACE inhibitors (ACEIs),
      angiotensin II receptor blockers (ARBs) and clonidine, were withdrawn for at
      least 2 weeks. Washout period for diuretics including spironolactone were 4
      weeks. Non-dihydropyridine calcium channel blockers (slow released verapamil)
      and/or alpha-blocker (terazosin) are allowed for controlling blood pressure when
      needed. If the serum potassium value<3.6 mmol/L, an oral potassium supplement was
      prescribed. After keeping upright position for 2 hours, blood samples were drawn
      for PRA and PAC measurement between 9:00AM-10:00AM. RESULTS: ARR was 100.00+/
      48.65 (14.19-285.16) pg/ml vs ngxml-1xh-1 in patients with essential hypertension
      and 699.33+/-213.33 (185.8-2150) pg/ml vs ngxml-1xh-1 in patients with
      adenoma/hyperplasia. ARR value was greater than 240 in 42 out of 45 patients
      (93.3%) with adenoma/hyperplasia and was less than 240 in 59 out of 65 (90.7%)
      patients with essential hypertension. We used ARR 240 as the cut-off threshold
      for screening primary aldosteronism in another 178 hypertensive patients and ARR
      was greater than 240 in all 15 patients with confirmed primary aldosteronism.
      CONCLUSION: It is suitable to use upright ARR 240 as a cut-off threshold for
      screening primary aldosteronism in Chinese hypertensive patients.

PMID- 17217709
TI  - [Aldosterone/plasma renin activity ratio is a sensitive parameter for screening
      patients with primary aldosteronism].
AB  - OBJECTIVE: To screen primary aldosteronism cases with ARR (aldosterone/plasma
      renin activity, ARR) from patients with hypertension, and to evaluate the
      diagnosis value of ARR in primary aldosteronism cases and analysis the clinical
      characters of primary aldosteronism cases. METHODS: Nine hundred and two patients
      with hypertension were collected, the plasma aldosterone concentration to plasma
      renin activity ratio were detected by radio-immunity method, after that, ARR were
      calculated. Retrospective analysis was made of clinical data in 126 primary
      aldosteronism cases, which ARR were over 25. RESULTS: One hundred and twenty-six
      cases (14%) were diagnosed as primary aldosteronism, and of them, 49 cases had
      hypokalemia. 25 patients received surgical operation and the rate of efficiency
      and cure of surgery treatment were 100% and 48%, respectively. The rate of
      efficiency and cure of drug treatment was 89% and 24% respectively. CONCLUSIONS:
      Primary aldosteronism affects over 10% of patients with hypertension in China.
      Patients with hypertension and most patients with treatment-resistant
      hypertension should undergo screening for primary aldosteronism with ARR. A high
      ARR is a positive screening test result, a finding that warrants confirmatory
      testing.

PMID- 17217710
TI  - [Efficacy and safety of olmesartan medoxomil versus losartan potassium in Chinese
      patients with mild to moderate essential hypertension].
AB  - OBJECTIVE: To evaluate the efficacy and safety of olmesartan medoxomil compared
      with losartan potassium in patients with mild to moderate essential hypertension.
      METHOD: This is a randomized, double-blind, double-dummy, active-controlled,
      parallel, multi-center study. After a 2-week placebo run-in period, a total of
      287 eligible subjects were randomized at 1:1 ratio to receive olmesartan
      medoxomil 20 mg or losartan potassium 50 mg, once daily for 8 weeks. The blood
      pressure was assessed after 4 weeks treatment. If the subject's seating diastolic
      blood pressure (SeDBP) was still >or=90 mm Hg, the dosage was doubled for another
      4 weeks; for those subjects whose SeDBP was <90 mm Hg after 4-week treatment, the
      initial dosage remained unchanged and the treatment continued until completion of
      the study. RESULTS: (1) The mean trough reduction in SeDBP from baseline in
      olmesartan group was significantly greater than that in losartan group after 4
      weeks (11.72 mm Hg vs 9.23 mm Hg, P=0.004) and 8 weeks treatment (12.94 mm Hg vs
      11.01 mm Hg, P=0.035). (2) The number and percentage of responders in olmesartan
      group (81, 65.3%) were statistically higher than those (68, 52.7%) in losartan
      group (P=0.028) after 4 weeks treatment and were similar between the two groups
      after 8 weeks treatment (P>0.05). (3) Individual and overall trough/peak ratios
      of DBP and SBP in 24-hour ambulatory blood pressure monitoring were higher in
      olmesartan group than losartan group. The hypotensive effect of olmesartan was
      more durable than losartan at 24 hour interval. (4) The incidence of study drug
      related adverse events (AEs) in olmesartan group (10.5%) was similar as that in
      losartan group (13.9%, P>0.05). Most of these AEs were mild and transient.
      CONCLUSION: This study shows that olmesartan medoxomil, at oral dose of 20 mg-40
      mg once daily was effective and safe for hypertension treatment and the
      hypotensive effect was superior to losartan potassium (50 mg-100 mg once daily).

PMID- 17217711
TI  - [The effects of angiotensin II receptor blockers in hypertensive patients
      complicating hyperuricaemia].
AB  - OBJECTIVE: To study the effects of angiotensin II receptor blockers (ARB),
      losartan and irbesartan, on blood pressure and serum uric acid (SUA) level in
      mild to moderate essential hypertensive patients complicating hyperuricaemia.
      METHODS: A total of 351 eligible patients were recruited in this multi-center,
      randomized, double-blind parallel clinical trial. After 1 week screening and a 2
      week single-blinded placebo wash-out period, patients were randomly assigned to
      receive losartan 50 mg (n=76) or irbesartan 150 mg (n=175) once daily for 4
      weeks, followed by a double-dose for another 4 weeks in patients whose seated DBP
      were >or=90 mm Hg or SBP>or=140 mm Hg at the end of 4 weeks. The SUA
      concentration and blood pressure were measured at baseline, 4 and 8 weeks post
      therapy. RESULTS: Three hundred and twenty-five patients completed the study (162
      in the losartan group and 163 in the irbesartan group). Both groups were well
      matched for baseline clinical characteristics and demographics. SUA was
      significant reduced in losartan group (430.93 micromol/L vs 372.35 micromol/L,
      P<0.0001), but not in Irbesartan group (430.46 micromol/L vs 420.67 micromol/L,
      P>0.05) 8 weeks post therapy compared to baseline level. Blood pressure was
      significantly and equally reduced in both groups after 8 weeks treatment compared
      to baseline level (P<0.0001). CONCLUSION: Losartan is an optimum choice of
      medication for patients with mild-to-moderate hypertension complicating
      hyperuricemia.

PMID- 17217712
TI  - [The beneficial effects of xuezhikang on top of extended-released nifedipine in
      hypertensive patients without severe hyperlipidemia].
AB  - OBJECTIVE: To investigate whether xuezhikang has additional beneficial effect on
      lipid peroxidation, myocardial fibrosis, inflammation and blood pressure control
      in hypertensive patients without sever hyperlipidemia treated with extended
      released nifedipine. METHODS: This is a randomized, single-blind, placebo
      controlled study, 100 patients with primary hypertension (HT) and normal or
      lightly elevated cholesterol level were randomized to receive placebo (n=49) or
      xuezhikang (1200 mg/d, n=51) for 24 weeks on top of extended-released nifedipine
      (20 mg, bid), 30 healthy volunteers served as controls. Plasma was obtained at
      baseline and 24 weeks after therapy. Lipids, C-reactive protein (CRP),
      malondialdehyde (MDA), superoxide dismutase photo-inhibition rate (SOD-PR) and
      type I collagen carboxypropeptide (PIP) were measured. RESULTS: Normal blood
      pressure (<140/90 mm Hg) was found in 49 out of 51 xuezhikang treated patients
      and in 40 out of 49 placebo treated patients (P<0.01) after 24 weeks therapy.
      Plasma CRP, MDA, SOD-PR and PIP were significantly higher in HT patients than
      those in normal controls. Plasma CRP, MDA, PIP and SOD-PR were significantly
      decreased in xuezhikang group while remained unchanged in placebo group after 24
      weeks treatment. CONCLUSION: In patients with primary hypertension without severe
      hyperlipidemia treated with nifedipine, xuezhikang treatment exerts additional
      beneficial effects including better blood pressure control, endothelial function
      improvement, lipid oxidation loading attenuation and anti-inflammation.

PMID- 17217713
TI  - [The beneficial effects of lipid-lowering therapy with xuezhikang on cardiac
      events and total mortality in coronary heart disease patients with or without
      hypertension: a random, double-blinded, placebo controlled clinical trial].
AB  - OBJECTIVE: To evaluate whether lipid-lowering therapy with Xuezhikang can reduce
      the risk of cardiac events and total mortality in coronary heart disease (CHD)
      patients with or without hypertension. METHODS: In this random, double-blinded,
      placebo controlled clinical trial, 2704 patients with hypertension and 2166
      patients without hypertension were enrolled and capsule Xuezhikang 0.6 g Bid or
      placebo on the top of conventional therapy without other lipid-lowering drugs.
      The mean follow-up period was four years. The primary end-points were nonfatal
      myocardial infarction and total mortality. RESULTS: Compared to placebo group,
      the incidence of cardiac events was reduced by 44.0% (P<0.0001) and 47.4%
      (P<0.0001) respectively in CHD patients with or without hypertension, and the
      total mortality was lowered by 35.8% (P=0.0012) and 28.6% (P=0.0737) respectively
      in CHD patients with or without hypertension. There was no significant difference
      in side effects between study groups. CONCLUSION: Xuezhikang can reduce the
      cardiac events and mortality in CHD patients with or without hypertension.

PMID- 17217715
TI  - [Chronotropic incompetence predicts angiographic severity in patients with
      coronary artery disease].
AB  - OBJECTIVE: To investigate the relationship between the chronotropic incompetence
      and angiographic severity in patients with coronary artery disease (CAD).
      METHODS: Coronary angiography was performed in 130 patients suspected for CAD and
      angiographic severity of coronary artery was quantitated by Duke score and
      Gensini score. Patients were divided to 4 groups: non-CAD group (39 patients),
      CAD group with one coronary artery involved (CHD1 group, 30 patients), CHD group
      with two coronary arteries involved (CHD2 group, 31 patients) and CAD group with
      three coronary arteries involved (CHD3 group, 30 patients). One month before
      coronary angiography, symptom-limited exercise treadmill tests were made and the
      ratio of heart rate reserve (HRR) and the percent maximal age-predicted heart
      rate achieved (rHR) were measured. RESULTS: rHR and HRR were significantly lower
      in CHD2 group (rHR 0.79+/-0.08, HRR 0.63+/-0.11) and CHD3 (rHR 0.78+/-0.07, HRR
      0.59+/-0.12) than that in non-CHD group (rHR 0.89+/-0.06, HRR 0.80+/-0.10) and
      CHD1 group (rHR 0.86+/-0.08, HRR 0.74+/-0.15, all P<0.05). rHR and HRR also
      significantly correlated with Duke score (r=-0.554, -0.578, all P<0.01) and
      Gennisi score (r=-0.453, -0.467, all P<0.01). CHD incidence rate was 75% in
      patients with positive rHR (or HRR) but without ST lowering during exercise.
      CONCLUSION: Chronotropic incompetence are negatively related to angiographic
      coronary severities and thus predict angiographic coronary severities. There is a
      high CAD incidence in patients with positive rHR (or HRR) but no ST lowering
      during symptom-limited exercise treadmill tests.

PMID- 17217716
TI  - [The hemodynamic effect of dobutamine stress on myocardial bridging-mural
      coronary artery].
AB  - OBJECTIVE: Patient with myocardial bridging (MB) usually has a benign prognosis,
      but some MB patients might experience myocardial ischemia, infarction and sudden
      cardiac death, especially during active physical activities. The purpose of the
      study was to study the stress-induced blood flow changes of the mural coronary
      artery in MB patients determined by intracoronary Doppler. METHODS: In 8 patients
      with MB, the basic average peak velocity (bAPV), hyperemic average peak velocity
      (hAPV) of blood flow, coronary flow reverse (CFR) proximal and distal to the
      mural coronary artery were measured before and during intravenously dobutamine
      (10 microg kg-1 min-1, then add 10 microg kg-1 min-1 at 3 min interval till 40
      microg kg-1 min-1) by intracoronary Doppler. RESULTS: The baseline mural coronary
      diameter reduction was (51.7+/-21.4)% and significantly increased to (90.0+/
      12.7)% (P<0.01) during dobutamine infusion. bAPV on the segments proximal and
      distal to the mural coronary artery significantly increased from (19.83+/-5.84)
      cm/s and (20.75+/-4.91) cm/s to (31.52+/-10.93) cm/s and (30.46+/-9.01) cm/s (all
      P<0.05 vs. baseline) respectively post dobutamine infusion. CFR measured at
      proximal and distal to myocardial bridging also significantly decreased from
      (2.91+/-0.62) and (2.46+/-0.82) to (2.17+/-0.66) and (1.83+/-0.51) (all P<0.01).
      CONCLUSION: Stress can significantly increase the compression of intramural
      coronary artery and reduce CFR on coronary segments both proximal and distal to
      the MB. Thus, active exercise might induce myocardial ischemia in patients with
      myocardial bridging.

PMID- 17217717
TI  - [Blood pressure changes post liver transplantation in 206 recipients].
AB  - OBJECTIVE: To study the blood pressure (BP) changes in the liver transplant
      recipients. METHODS: A total of 206 patients without preoperation hypertension
      received liver transplantation in our hospital from February 2001 to July 2005.
      The BP level and serum immunosuppressant concentration at preoperation and
      various time points post operation were determined. RESULTS: Compared with the
      preoperation, the average systolic and diastolic pressure was significantly
      increased at the 2 week, 1, 2, 4 and 6 months post operation. The mobility of
      hypertension increased significantly after liver transplantation, with the
      highest mobility (46.49%) at the 1st month post operation. There was no linear
      correlation between the immunosuppressant (FK506) concentration and the BP level
      at any time point. CONCLUSION: There was a high hypertension incidence after
      liver transplantation. Although the use of immunosuppressive drugs accompanied
      with the BP increase, there was no linear correlation between the
      immunosuppressant concentration and the BP level post operation.

PMID- 17217721
TI  - [Erythropoietin enhances the therapy potency of autologous bone marrow stromal
      cells in a rat heart infarction model via phosphatidylinositol-3-kinase/Akt
      pathway].
AB  - OBJECTIVES: Erythropoietin (EPO) induces angiogenesis and inhibits apoptosis
      through the phosphatidylinositol-3-kinase/Akt (PI3-K/Akt) pathway.
      Transplantation of mesenchymal stromal cells (MSC) has been shown to improve
      heart perfusion and function post myocardial ischemia. We investigated whether
      EPO enhances the therapeutic potency of MSC transplantation in rats with
      experimental myocardial infarction (MI). METHODS: Wistar rats were divided into
      four groups (n=8 each): myocardial infarction (MI) group, EPO group, MSC group
      and MSC-EPO group. MI was made by ligating the anterior descending coronary
      artery. MSC was injected in the infarcted area immediately after ligation in MSC
      group and MSC-EPO group. EPO (3000 U/kg) was administered i.p. in EPO group and
      MSC-EPO group for 3 days post MI and on the 14th to 16th day post MI. Cardiac
      function was measured by echocardiography at 2 and 21 days after MI. MI size was
      measured, and the level of phosphorylated Akt was assessed by Western blot and
      immunohistology at 21 days post MI. RESULTS: LVEF was significantly lower at 21
      days than that at 2 days in MI group while significantly increased in other 3
      groups, especially in MSC-EPO group at 21 days than that at 2 days. MI size was
      significantly lower (20.7%+/-2.3% vs. 24.0%+/-2.3%, 26.0%+/-0.9%, 28.1%+/-1.5%,
      all P<0.05), capillary density was significantly higher (12.95+/-2.11 vs. 10.78+/
      0.99, 10.43+/-1.52 and 6.31+/-0.69, all P<0.05) in MSC-EPO group at 21 days than
      that in other groups and the ratio of phosphorylated Akt to total Akt measured by
      Western blot was also significantly higher in MSC-EPO group than other groups
      (0.36 vs. 0.32, 0.31 and 0.28, all P<0.05). Compared to other groups, Bcl-2 was
      significantly up-regulated and Bax down-regulated in MSC-EPO group. CONCLUSION:
      Our results demonstrated that MSC transplantation and EPO infusion could improve
      cardiac function and EPO enhances the therapeutic potency of MSC transplantation
      via PI3-K/Akt pathways.

PMID- 17217722
TI  - [Pacemaker current gene expression of rat mesenchymal stem cells and
      identification of mesenchymal stem cells expressing human pacemaker current gene
      (hHCN2)].
AB  - OBJECTIVE: To study pacemaker current gene expression of mesenchymal stem cells
      (MSCs) and the electrophysiological property of MSCs expressing human pacemaker
      current gene. METHODS: Pacemaker current gene expression of MSCs were studied by
      real-time quantitative polymerase chain reaction (real-time PCR) and pcDNA3-hHCN2
      was transfected with Lipofectin 2000 into MSCs. hHCN2 expression at mRNA and at
      protein levels in the transfected cells were identified by real-time PCR and
      Western blot, respectively. The ionic currents of cloned hHCN2 (IhHCN2) were
      recorded and the current characteristics were studied through the whole-cell
      patch clamp technique. RESULTS: mHCN1, mHCN2, mHCN3, mHCN4 represent (0.08+/
      0.01)%, (77.16+/-0.03)%, (0.24+/-0.01)%, (22.53+/-0.02)% of total HCN mRNA in
      MSCs as determined by real-time PCR. Transfected hHCN2 ionic currents were
      recorded by whole-cell patch clamp and current density-voltage curves were
      obtained. The threshold for activation of IhHCN2 was approximately -80 mV and
      this current could be blocked by Cs+ (4 mmol/L). hHCN2 expression in transfected
      MSCs was detected both at mRNA and protein levels. CONCLUSIONS: 1. mHCN2 and
      mHCN4 represent the major populations of total HCN mRNA in MSCs. 2. Plasmid
      pcDNA3-hHCN2 by Lipofectin could be successfully transfected into MSCs with
      IhHCN2 recorded by whole-cell patch clamp technique, this study provides a basis
      for future antiarrhythmic gene therapy.

PMID- 17217723
TI  - [Effects of valsartan and captopril on expressions and activities of tissue
      factor and tissue factor pathway inhibitor].
AB  - OBJECTIVE: To investigate the effects of ox-LDL, ACEI and ARB on expressions and
      activities of TF and TFPI in VSMC. METHODS: (1) Rabbit VSMC was cultured by
      explant-attached method in vitro. (2) The effects of ox-LDL and valsartan on TF
      and TFPI expressions were analyzed by immunohistochemistry and
      immunofluorescence. Laser scanning confocal microscopy were applied to analyze
      the effects of ox-LDL and valsartan on TF expression. The effects of ox-LDL,
      valsartan and captopril on TF and TFPI antigen expressions were analyzed by
      ELISA. Chromogenic substrate method was used to determine the effects of ox-LDL,
      valsartan and captopril on TF activity. The effects of ox-LDL and valsartan on TF
      mRNA expression were analyzed by RT-PCR. RESULTS: (1) ox-LDL could upregulate TF
      antigen, activity and TF expression at mRNA level and downregulate TFPI antigen.
      (2) Valsartan and captopril could reduce TF antigen and activity in VSMC treated
      by ox-LDL, and valsartan reduce it in a dose-dependent manner. Valsartan could
      also attenuate TF expression at mRNA level in VSMC treated by ox-LDL. (3) Using
      ELISA, valsartan and captopril could also enhance TFPI antigen in VSMC treated by
      ox-LDL. CONCLUSION: Our study showed upregulated TF and downregulated TFPI
      expression and activity by ox-LDL and these effects could be reversed by ACEI and
      ARB indicating a new insight on the antiatherosclerotic effects of ACEI and ARB.

PMID- 17217724
TI  - [Porcine MSC-derived CLC induced by rabbit's cardiomyocytes extract did not
      induce immune reaction in vivo].
AB  - OBJECTIVE: To compare the in vivo immune reaction of transplanting porcine MSC
      derived CLC with rabbit cardiomyocytes extracts induced differentiation or in
      vitro cultured porcine MSC. METHODS: After injecting the MSC-derived CLC or MSC
      to the original porcines, the number of CD4+, CD8+ T cells were determined by
      flow cytometry. The serum concentrations of IL-2, IL-4 were measured by ELISA,
      and the porcine spleen lymphocyte CTL cytotoxicity was determined by Cell
      Counting Kit-8 Assay. RESULTS: The numbers of CD4+ and CD8+ T cells, the serum
      concentrations of IL-2, IL-4 and spleen lymphocyte CTL cytotoxicity were all
      similar in porcines received MSC-derived CLC induced by rabbit's CMs extract or
      MSC transplantation. CONCLUSION: The porcine MSC-derived CLC induced by rabbit's
      CMs extract did not induce extra immune reaction when injected back to the
      original porcine.

PMID- 17217725
TI  - [The protective effect of PEP-1-CAT fusion protein on hydrogen peroxide-induced
      oxidative stress injury in human umbilical vein endothelial cells].
AB  - OBJECTIVE: To investigate the transduction ability of PEP-1-CAT fusion protein
      into human umbilical vein endothelial cell (HUVECs) and the effects on hydrogen
      peroxide (H2O2)-induced oxidative stress injury in these cells. METHODS: With the
      use of TA-cloning program and isocaudamer technique, the pET15b-PEP-1-CAT of
      prokaryotic expression plasmid was successfully constructed. The recombinant
      plasmid was transformed into E.coli BL21 (DE3) and the protein expression was
      induced by IPTG. The recombinant protein has an N-terminal His-tag which could be
      used to purify the target protein by affinity chromatography on a Ni2+-NTA-resin
      column. The fusion protein PEP-1-CAT was prepared and confirmed by specific
      enzyme activity in vitro. The purified PEP-1-CAT fusion protein was added on
      cultured HUVECs in vitro. The transduction ability of PEP-1-CAT fusion protein
      into cells was analyzed by Western blot and specific enzyme activity. The cells
      were treated with H2O2 (0.5 mmol/L) alone and in combination with PEP-1-CAT
      fusion protein for 4 h. Then, the cell viability, lactate dehydrogenase (LDH) and
      malondialdehyde (MDA) contents were measured. RESULTS: The PEP-1-CAT fusion
      protein could be transduced into the cultured HUVECs in a dose- and time
      dependent manner and be stable for at least 48 h. After H2O2 administration, cell
      viability was significantly reduced compared with control group (37.23%+/-5.68%
      vs. 100%, P<0.05), while LDH leakage (849.3 U/L+/-95.1 U/L) and MDA (8.23
      nmol/L+/-1.58 nmol/L) content were significantly higher than that in control
      group (540.6 U/L+/-65.7 U/L and 2.46 nmol/L+/-1.42 nmol/L, respectively, all
      P<0.05). Preincubation with PEP-1-CAT proteins at various concentrations (0.25-2
      micromol/L) significantly attenuated H2O2-induced cell injury. CONCLUSION: The
      PEP-1-CAT fusion protein could efficiently penetrate HUVECs and the transduced
      protein could attenuate cellular oxidative stress injury induced by H2O2. The PEP
      1-CAT fusion protein might be a new strategy for preventing and treating
      oxidative stress induced diseases.

PMID- 17217734
TI  - [Advancement in pharmacogenomics of beta-blocker therapy].

PMID- 17217735
TI  - [Real-time three-dimensional echocardiography: imaging method, research status
      and its future].

PMID- 17217737
TI  - [Abnormal glucose metabolism in patients with coronary artery diseases].

PMID- 17217738
TI  - [Metabolic syndrome: disputes along side progress].

PMID- 17217739
TI  - [Standardizing epilepsy treatment for improved cost-effectiveness].

PMID- 17217741
TI  - [The efficacy and safety of antithrombotic therapy with warfarin in nonrheumatic
      atrial fibrillation].
AB  - OBJECTIVE: To identify the optimal intensity of anticoagulation with warfarin in
      patients with nonvalvular atrial fibrillation by studying the relation between
      the thromboembolic and hemorrhagic events. METHODS: Nonvalvular atrail
      fibrillation patients randomized to receive adjusted-dose warfarin [international
      normalized ratio (INR) 2.0 to 3.0] were included. The initial dose of warfarin
      was 2 mg and the dose was then adjusted to target at INR 2.0-3.0. Thromboembolic
      events and bleeding events were identified during follow-up. RESULTS: Of the 335
      patients, 204 (60.9%) were male. Mean age was (62.6 +/- 10.3) years. Sixty-six
      percent of all the patients had at least one risk factor for thromboembolism. The
      median follow-up period was 19 months (range 2-24 months). Among the 3482 INRs
      measured during the study, 2378 were in the target range. Of the 19
      thromboembolic events occurred during warfarin therapy, 15 occurred with INR less
      than 2.0. The independent risk factors for thromboembolic events during warfarin
      therapy were age > 75 years, history of stroke, left ventricular ejection
      fraction (LVEF) < 0.40 and INR > 2.0. The incidence of bleeding events were 6.9%,
      including 5 cases (1.5%) of minor bleeding and 18 cases (5.4%) of major bleeding.
      The independent risk factors for the hemorrhage in warfarin treatment are age >
      75 years, systolic blood pressure > or = 160 mm Hg, elevated serum creatinine
      level INR > 3.0. INR of 2.0 to 3.0 was associated with the lowest combined rate
      of bleeding and thromboembolism. CONCLUSIONS: INR > 3.0 should be avoided to
      minimize the bleeding complications. Under intense monitoring, adjusted-dose
      warfarin (INR 2.0 - 3.0) is effective and safe for the moderate to high risk
      nonvalvular atrial fibrillation patients.

PMID- 17217742
TI  - [The long-term results percutaneous transluminal angioplasty and stenting in
      atherosclerotic renal artery stenosis].
AB  - OBJECTIVE: To evaluate the safety, as well as short term and long term effect of
      percutaneous angioplasty and stenting in atherosclerotic renal artery stenosis.
      METHODS: A total of 150 consecutive patients with atherosclerotic renal artery
      stenosis (ARAS) undergoing percutaneous transluminal renal angioplasty (PTRA) and
      stenting in a period of 6 years were followed up. Blood pressure, renal function
      before and after the procedure were monitored through-out the follow up years.
      Renal artery restenosis was tested with ultrasound and Doppler 6-9 months after
      the procedure. Clinically drive repeat angiogram was done in some patients.
      RESULTS: 96% of the patients had coronary artery disease and 54% triple vessel
      disease. A total of 174 renal arteries were found to have severe ARAS in these
      150 patients. Procedure success rate was 99.3% with only 1 failure. 3 total
      occluded renal artery were not attempted, with a total of 170 renal arteries
      receiving PTRA and stenting. There was no immediate complication such as death,
      renal artery rupture or acute closure. 145 patients were clinically followed up,
      with a follow-up rate of 98.6%, and a follow up time between 7 months and 5
      years. During follow-up, another 2 patients died in addition to the 3 died in the
      hospital. All of them died of cardiovascular disease. As to blood pressure, 66
      patients among 101 with refractory hypertension and 20 among 42 with well
      controlled hypertension got improved in 6-9 months of follow up, with an
      improvement rate of 60.1%. These effects were kept throughout the follow up
      years. Most of the patient's renal function kept stable and a small number of
      patient's serum creatine level ameliorating. Renal artery restenosis was found in
      10 among the 166 renal vessels undergoing ultrasound examination, with a
      restenosis rate of 6.0%. CONCLUSION: PTRA and stenting in ARAS patients with
      coronary artery disease are safe and effective, most of the patient's blood
      pressure can be controlled and renal function can be kept stable. Restenosis rate
      is quite low and acceptable.

PMID- 17217743
TI  - [Collagen type I and interleukin-1 beta gene expression in human atria during
      atrial fibrillation].
AB  - OBJECTIVE: To determine whether gene expression of collagen type I and
      interleukin-1 beta (IL-1beta) is altered in patients with atrial fibrillation
      (AF). METHODS: Right atrial tissue samples were taken from 75 patients with
      rheumatic heart disease who underwent heart valve replacement surgery. 34
      patients had no history of AF, 11 patients had paroxysmal AF and 30 patients had
      persistent AF. The mRNA content of collagen type I and IL-1beta was measured with
      semi-quantitative RT-PCR. RESULTS: The mRNA content of collagen type I was
      significantly increased in the persistent AF group (P < 0.001) and increased in
      the paroxysmal AF group (P < 0.05) as compared with that in the sinus rhythm
      group. The mRNA content of IL-1beta was up-regulated in the persistent AF group
      (P < 0.05), but the trend of increase did not reach statistical significance in
      the paroxysmal AF group (P > 0.05). The mRNA content of IL-1beta was
      significantly correlated with the mRNA content of collagen type I (r = 0.295, P =
      0.011), left atrial dimension (r = 0.385, P = 0.001) and AF duration (r = 0.326,
      P = 0.004). CONCLUSION: The upregulation of IL-1beta gene expression in atrium
      may contribute to the atrial fibrosis during AF through influencing collagen
      metabolism.

PMID- 17217744
TI  - [The effect of Xuezhikang on ventricular diastolic function in hypertension].
AB  - OBJECTIVE: To investigate whether statins have effect on diastolic function of
      both left and right ventricles in hypertensive patients. METHODS: This is a
      randomized, mono-blind, placebo-controlled study. 120 systemic hypertensive (HT)
      patients with normal or slightly elevated cholesterol were randomized to placebo
      or Xuezhikang (1200 mg/d) for 24 weeks. Extended-release nifedipine was
      administrated to the HT patients. 30 healthy volunteers served as controls.
      Plasma were obtained at baseline and 24 weeks after Xuezhikang therapy.
      Cholesterol and carboxy-terminal peptide of procollagen type I (PIP) were
      measured. Early diastolic velocity (Em) and late diastolic velocity (Am) were
      obtained from right atrioventricular ring and left atrioventricular ring with
      pulsed wave tissue Doppler imaging. RESULTS: The levels of plasma PIP were higher
      in HT patients. After 24 weeks, the levels of plasma LDL-C, TC and PIP were
      significantly lower in Xuezhikang group than those in placebo group; Systolic and
      diastolic pressure were decreased both in placebo group and Xuezhikang group
      meanwhile pulse pressure was decreased and Em/Am ratio at left atrioventricular
      ring was higher in Xuezhikang group as compared with those in placebo group.
      CONCLUSION: In systemic hypertensive patients, Xuezhikang exerts a beneficial
      effect on diastolic function of left ventricule via controlling blood pressure,
      lowering blood lipid and inhibiting myocardial fibrosis.

PMID- 17217745
TI  - [Risk factors for cardiovascular autonomic neuropathy and their prognostic
      implications in type 2 diabetes mellitus].
AB  - OBJECTIVE: Risk factors for diabetic cardiovascular autonomic neuropathy (CAN) in
      patients with type 2 diabetes were analyzed to establish a regression model for
      evaluating the diagnosis of CAN. METHODS: 325 patients with type 2 diabetes were
      divided into four groups according to the results of four standard function
      tests. Every patient was required to offer detailed disease history and accept
      physical examination, serum and urine tests and examinations including ECG, nerve
      conduction velocity, retinoscope and Doppler of carotid and lower limb arteries.
      RESULTS: 64.0% of the patients had abnormal autonomic function and 30.2% definite
      CAN. There was significant difference among groups about age, average
      glycosylated forms of hemoglobin (HbA1c), systolic blood pressure, corrected 24 h
      albumin excretion and heart rate at rest (P < 0.001). The incidence of diabetic
      complications and accompanying diseases increased with deterioration of CAN (P <
      0.05). The regression model showed that age, average HbA1c, hypertension,
      peripheral neuropathy, retinopathy, tachycardia at rest and duration of
      peripheral neuropathy were significant related factors for CAN. With these
      factors, a mathematic formula was established which could be used for evaluating
      the diagnosis of CAN. CONCLUSION: Except for age and hypertension, risk factors
      were all induced by hyperglycemia. It is suggested that control of hyperglycemia
      is of primary importance in preventing diabetic complications.

PMID- 17217746
TI  - [Avian influenza (H5N1) cured successfully in human: a case report].
AB  - OBJECTIVE: To improve understanding of avian influenza in humans by presenting a
      case of avian influenza (H(5)N(1)). METHODS: Clinical and laboratory data of this
      case of avian influenza (H(5)N(1)) in humans were described, and related
      literature was reviewed. RESULTS: The female patient was 31 years old. She lived
      in epidemic district of avian influenza and had a history of close contact with
      sick poultry. The patient initially presented fever and chills accompanied by
      myalgia, and then followed by cough, blood-tinged sputum, dyspnea and frequent
      diarrhea. Laboratory findings indicated leukopenia, dysfunction of cellular
      immunity, abnormal enzymes of liver, and hypoxia. Patchy infiltration involved
      two lungs progressed rapidly on chest radiograph. ECG showed that T waves of V(1 
      5) were reverted. The patient was diagnosed with avian influenza (H(5)N(1)) by
      hemagglutination inhibition and microneutralization assay combined with
      epidemiological and clinical data. Supportive therapy, corticosteroids,
      antibacterial, and antiviral agents were administered. Complications were treated
      accordingly during the course. She got better overtime and recovered. The
      laboratory abnormalities and chest radiograph returned to normal before
      discharge. The patient's relatives and doctors involved in the medical care were
      free from infection. CONCLUSIONS: Supportive treatment is important for patients
      with avian influenza. Complications should be prevented and treated in time.

PMID- 17217747
TI  - [The relationship of nature killer cell 2D gene polymorphisms and ulcerative
      colitis in the Chinese].
AB  - OBJECTIVE: Nature killer cell 2D (NKG2D) is an important activated cytokine that
      has been implicated in the inflammatory reaction and immune response. The
      function and the location of NKG2D gene show it is an ideal susceptibility gene
      to ulcerative colitis (UC). We evaluated the NKG2D gene polymorphisms in patients
      of Zhejiang province to determine whether the gene is associated with
      susceptibility to UC in Chinese Han population. METHODS: Blood samples were
      obtained from 110 patients with UC and 292 healthy controls in Zhejiang location.
      Genotyping for 2 common NKG2D (10676G/, 908A/) polymorphisms was carried out
      using polymerase chain sequence with specific primer. RESULTS: NKG2D was not
      associated with disease (908A allele frequency patients 19.1% vs controls 16.3%,
      P > 0.05). None of the patients with UC had 10676G heterozygous or homozygous
      variants. Similarly none of the health controls. CONCLUSIONS: The common variants
      in NKG2D are not associated with UC in the Chinese Han population. Research of
      larger sample's queue, analysis from different layer and DNA sequence will help
      to determine the function of NKG2D in the process of UC.

PMID- 17217748
TI  - [The effect and mechanism of cholecystokinin octapeptide induced-gastric
      dysmotility on bile regurgitation during stress].
AB  - OBJECTIVE: To illustrate the existence of bile regurgitation under stress
      condition, and explore the possible effects and related mechanism of changes of
      cholecystokinin octapeptide (CCK-8) on stress-induced bile regurgitation in rats.
      METHODS: (1) Changes in plasma CCK-8 and gastric bile concentration were measured
      by using radioimmunoassay while simultaneously calculating gastric ulcer index
      and intragastric pH; (2) Each isolated gastric strips were suspended in a tissue
      chamber to record the contractile responses by polyphysiograph; (3) The
      responsiveness of gastric smooth muscle cells (SMCs) to sulfated cholecystokinin
      octapeptide (CCK-8S) were examined using fura-2-loaded microfluorimetric
      measurement of intracellular calcium concentration ([Ca(2+)] i); (4) The current
      of L-type calcium channels (I(CaL)) of SMCs were recorded by patch-clamp
      techniques. RESULTS: (1) Compared with the normal control, plasma CCK-8 [from
      (2.23 +/- 0.88) pmol/L to (10.80 +/- 3.82) pmol/L] and gastric bile concentration
      [from (37.93 +/- 23.76) micromol/L to (1316.00 +/- 197.36) micromol/L]
      significantly increased during the stress (P < 0.01) and both simultaneously
      reached the peak at the time point of 2 h after stress; ulcer index (from 0.62 +/
      0.23 to 32.01 +/- 16.11) and intragastric pH (from 1.06 +/- 1.20 to 5.29 +/-
      1.25) apparently increased (P < 0.01); (2) Significant changes to CCK-8S were
      found in the mean contractile amplitude and frequency of circular muscle and
      longitudinal muscle of gastric antrum and pylorus; (3) CCK-8S-evoked significant
      increase in [Ca(2+)] i [from (65.8 +/- 7.4) nmol/L to (472.1 +/- 35.6) nmol/L, P
      < 0.01] could be suppressed by CCK-A receptor antagonist; whereas a small but
      significant increases were still elicited by CCK-8S under condition of the
      removal of extracellular calcium; (4) CCK-8S-intensified calcium current I(Ca-L)
      [from (-56.42 +/- 6.57) pA to (-88.54 +/- 5.71) pA, P < 0.01)] apparently
      inhibited by respective administration of nifedipine, Ca(2+)-ATPase inhibitors or
      calcium dependent chloride channel blocker (P < 0.01). CONCLUSIONS: Gastric
      mucosal damage induced by bile regurgitation is closely connected with gastric
      antrum and pylorus dysmotility evoked by CCK-8 during the stress. CCK-8S-evoked
      [Ca(2+)] i increase in gastric antrum and pylorus SMC depends on the release of
      intracellular calcium stores which activates L-type voltage-dependent calcium
      channels through the activation of calcium dependent chloride channels.

PMID- 17217749
TI  - [The expression of SMN2 gene mRNA in neuron-like cells derived from patients with
      spinal muscular atrophy].
AB  - OBJECTIVE: To detect the difference of SMN2 mRNA expression between the neuron
      like cells (NLCs) derived from patients with spinal muscular atrophy (SMA).
      METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) was performed to diagnose the patients with SMA and the controls.
      Mesenchymal stem cells (MSCs) were induced into neuron-like cells which become
      the models of neurons. The transcripts of SMN2 were testified with RT-PCR
      combined with sequencing. RESULTS: Two bands (266 bp and 212 bp) were found in
      the gel picture of RT-PCR and the band of 266 bp was the full length transcript
      (fl-SMN mRNA). The band of 212 bp was testified by sequencing to be deletion of
      the exon 7, which was the production of alternative splicing (skipping exon 7,
      SMNDelta7 mRNA). The expression of fl-SMN mRNA accounted for 23.2% of the total
      SMN mRNA in the SMA patients, being much lower than the rate in the controls
      (82.0%). In contrast, 76.8% of SMN gene transcripts was SMNDelta7 mRNA in the SMA
      patients, being much higher than the rate of 18% in the controls. CONCLUSIONS:
      Alternative splicing exists in SMN2 gene transcription, that is, exon 7 is
      skipped during the processing of SMN2 mRNA in the NLCs of SMA patients, which is
      one of the reasons of the full-length SMN protein lacking.

PMID- 17217750
TI  - [The role of CD4+ CD25+ T cell and FOXP3 in hsot acute graft rejection].
AB  - OBJECTIVE: To explore the relationship among CD4+ CD25+ regulatory T cell, the
      expression of FOXP(3) mRNA levels of donor bone marrow (BM) and graft versus host
      disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT).
      METHODS: (1) Thirty patients undergoing allo-HSCT were enrolled in this study.
      The levels of donor CD4+CD25+ regulatory T cell were compared in the patients
      with GVHD and those without GVHD with immunofluorescence and flow cytometry. (2)
      The donor BM expressions of FOXP(3) mRNA levels were analyzed by using reverse
      transcriptase polymerase chain reaction (RT-PCR). RESULTS: (1) All patients
      achieved engraftment. The median time for ANC > or = 0.5 x 10(9)/L and PLT > or =
      20 x 10(9)/L were attained at day 14 (range, 12-15) and day 18 (range, 15-25)
      respectively. With a median follow-up of 12.8 (8-16) months, acute GVHD (aGVHD)
      occurred in 15 of the 30 patients (50.0%) with grade II-IV aGVHD (40.0%). Chronic
      GVHD developed in 6 (extensive 2, limited 4) out of the 30 patients (20.0%). (2)
      The levels of donor CD4+CD25+ regulatory T cell pre-and post-mobilization were
      (2.67 +/- 0.38)% and (5.01 +/- 1.33)% respectively; no difference was observed (P
      > 0.05). (3) Patients with I-II aGVHD demonstrated higher donor-type CD4+CD25+
      immune regulatory T cell level than those with III-IV aGVHD. Patients with III-IV
      aGVHD showed much lower donor-type CD4+CD25+ immune regulatory T cell level than
      those without GVHD. No difference was observed between the patients withI-II
      aGVHD and those without aGVHD. (4) The transcripts of FOXP(3) donor BM were
      detected in seven donors for the thirty recipients who received allo-HSCT. Among
      the seven patients who received stem cells from these donors five had no GVHD
      after transplantation and the remaining two developed I aGVHD. Donor BM FOXP(3)
      transcripts were never detected in patients with II-IV aGVHD. CONCLUSIONS: (1)
      Donor-type CD4+CD25+ immune regulatory T cell level was related to recipient II
      IV aGVHD. Up-grade donor-type CD4+CD25+ immune regulatory T cell level could
      reduce the incidence of aGVHD. (2) Donor BM FOXP(3) transcripts were detected in
      patients without serious aGVHD after transplantation.

PMID- 17217775
TI  - [Emphasizing on reconstruction of postoperative binocular vision in children with
      eye disease].
AB  - Postoperative refractive correction, therapy of amblyopia and binocular visual
      function training are indispensable procedures for obtaining better effects after
      the operation for various common pediatric eye disease, e.g., strabismus and
      amblyopia, cataract, glaucoma and retinal detachment, etc.. Advancement in
      research of binocular vision development has provided new potentialities of
      reconstructing postoperative binocular vision in children with eye disease
      clinically. Along with improving visual acuity, we should be concern about
      reconstruction of postoperative binocular vision and try to decrease stereoblind,
      which can provide children with better visual function and help them adapt to
      modern social life.

PMID- 17217776
TI  - [Diagrammatic presentation of the results of strabismus examination in the
      various diagnostic positions of gaze need standardization].
AB  - We have found that there is no consistent opinion about the recording of the
      results of ocular deviations in various diagnostic positions of gaze, as well as
      for head tilt tests to the right and to the left in textbooks, manuscript and
      hospital medical records in China. For the sake of convenience in analysis and
      diagnosis of ocular deviations, it is necessary to have a unified opinion in
      recording these results. In accordance with the habitual diagrammatic
      presentation of the results of ocular deviations in the various diagnostic
      positions of gaze, as well as for head tilt tests to the right and to the left at
      home and abroad, we recommend two recording methods: the examiner's view and the
      patient's view. The patient's view is used in the synoptophore readings, Worth
      four-dot test, Maddox rod and double Maddox rod test, diplopia test, Hess screen
      and Lancaster screen test. The examiner's view is used in the prism cover test
      and arrangement for pictures in nine ocular positions of gaze.

PMID- 17217777
TI  - [Study of functional magnetic resonance imaging in strabismic and anisometropic
      amblyopic patients].
AB  - OBJECTIVE: To elucidate the difference in the pathogenesis between strabismic
      amblyopia and anisometropic amblyopia. METHODS: Using an EPI gradient echo
      sequence in 1.5 T MRI and visual electrophysiological system, the pattern visual
      evoked potentials and calcarine activation by monocular viewing of check-board
      pattern with reversal were examined in 18 strabismic amblyopes and 15
      anisometropic amblyopes. The calcarine activation in terms of binocular voxels
      index and dependence on the spatial frequency of the stimuli were compared. The
      correlation between PVEP P(100) latency and activation intensity was also
      analyzed. RESULTS: The binocular voxels index was lower in the strabismic
      amblyope than that in the anisometropic amblyope. The calcarine activation from
      amblyopic eyes in strabismic amblyopes was more suppressed at higher spatial
      frequencies (1, 2 c/d); while that from amblyopic eyes in anisometropic amblyopes
      was more suppressed at all spatial frequencies (0.25, 0.5, 1 and 2 c/d). Inverse
      correlations existed between PVEP P(100) latency and activation intensity in two
      types amblyopia (P < 0.05). CONCLUSIONS: The binocular interaction is not equal
      in these two different types of amblyopia. Meanwhile, the amblyopia-related
      deficits in the low and high-spatial-frequency pathway of visual system are not
      similar between these two different types of amblyopia.

PMID- 17217778
TI  - [Study on crossed and uncrossed disparity evoked potential of dynamic random dot
      stereogram].
AB  - OBJECTIVE: To analyze the disparity evoked potentials (DEP) of fine disparities,
      coarse disparities, crossed disparities and uncrossed disparities and provide
      parameters of impersonal examining stereopsis. METHODS: A software package for
      generating dynamic random dot stereogram (DRDS) was developed as a visual
      stimulus to elicit DEP in 30 normal subjects. The DEP of every subject was
      recorded in different crossed and uncrossed disparity stimuli (4', 8', 15', 23',
      30', 45', 53', 60', 72', 87', 102', 124', 150' of arc). RESULTS: (1) the constant
      negative-positive complex wave was observed in different disparity stimuli. (2)
      The N wave's latency of -45' was the longest, the N wave's latency of -150' was
      the shortest among crossed disparities. The N wave's latency of 4', 23' was the
      longest, the N wave's latency of 124' was the shortest among uncrossed
      disparities. (3) The amplitude peak of P wave occurred at -23', -60', -150' among
      crossed disparities. The amplitude peak of P wave occurred at 15', 45', 72' among
      uncrossed disparities. (4) All characteristic crossed disparities were smaller
      than the uncrossed disparities. The change orderliness of small crossed
      disparities was different from that of small uncrossed disparities. CONCLUSIONS:
      The N wave's latency and the P wave's amplitude can be used as parameters to
      impersonally examine stereopsis. These results suggest that stereopsis can be
      divided into fine crossed stereopsis, fine uncrossed stereopsis, coarse crossed
      stereopsis, and coarse uncrossed stereopsis.

PMID- 17217779
TI  - [The effect of weakening the overaction superior oblique muscles on the status of
      ocular torsion].
AB  - OBJECTIVE: To investigate the effect of weakening the superior oblique muscles on
      the status of ocular torsion. METHODS: Twenty-nine patients (58 eyes) underwent
      tenotomy or partial ectomy of bilateral superior oblique muscles for treatment of
      superior oblique overacting. Objective cyclodeviations were assessed by fundus
      photograph before and 7 days after the surgery. The photographs were transferred
      to a computer and then the fovea-disc angle was measured by a software for
      drawing pictures. Subjective cyclodeviations and binocular vision function were
      assessed by synoptophore. RESULTS: Fundus photography before surgery revealed
      that the intorsion was 10.48 degrees +/- 6.01 degrees for the right eye and was
      9.37 degrees +/- 5.88 degrees for the left eye. The reduction of the
      cyclodeviations by weakening the superior oblique muscle for the right and left
      eye was 9.11 degrees +/- 7.09 degrees and 7.94 degrees +/- 4.76 degrees
      respectively. The comparisons of objective ocular torsion for both eyes showed
      high significant differences (P < 0.01) pre- and post-operatively. There were no
      significant differences (P > 0.05) between the effects of tenotomy or partial
      ectomy of bilateral superior oblique muscles. All patients showed no cyclotropia
      and normal binocular vision function was obtained with synoptophore before and
      after surgery. CONCLUSIONS: Weakening the overaction superior oblique could
      correct ocular incyclodeviation. Both tenotomy and partial ectomy of bilateral
      superior oblique muscles can treat ocular incyclodeviation effectively. The
      changes of subjective and objective cyclodeviations are inconsistent with each
      other.

PMID- 17217780
TI  - [Intraocular lens power calculation in cataract phacoemulsification after
      refractive surgery].
AB  - OBJECTIVE: To analyze the results of phacoemulsification cataract surgery in eyes
      that had refractive surgery and to compare the predictability of K value in
      Holladay II formula of intraocular lens power calculation. METHODS: Fifteen cases
      (15 eyes) were divided into 2 groups. Group 1 included 8 eyes, the IOL power was
      calculated with Holladay II formula and the K value was calculated using surgeon
      entered k-value (KS). Group 2 included 7 eyes, the IOL power was calculated with
      Holladay II formula also, the K value was calculated using k-value from
      refractive data (KR). The achieved refraction after phacoemulsification was
      compared with target refraction to assess the predictability of the formula and
      the accuracy of k-value. RESULTS: The mean difference between target and achieved
      refractions after phacoemulsification was (0.90 +/- 0.22) D in group 1 and (0.99
      +/- 0.22) D in group 2. CONCLUSIONS: Holladay II formula is accurate in the IOL
      power calculation after refractive surgery. There is no significant difference
      between the results calculated by Holladay II formula with KS or KR.

PMID- 17217781
TI  - [Clinical analysis of 11 cases of orbital Langerhans cell histiocytosis].
AB  - OBJECTIVE: To study the clinical and imaging features, the diagnosis and
      management of orbital Langerhans cell histiocytosis. METHODS: The symptoms,
      signs, imaging features, treatment and follow-up results of 11 cases of orbital
      Langerhans cell histiocytosis were reviewed and analyzed, including 7 cases of
      eosinophilic granuloma and 4 cases of Hand-Schueller-Christian disease. RESULTS:
      Eosinophilic granuloma occurred primarily in children and teenagers and appeared
      as orbital lesions only. Hand-Schueller-Christian disease occurred in children
      under 5 years old, with multiple lesions of histiocytosis. Typical cases showed
      the Hand-Schueller-Christian triad: exophthalmos, diabetes insipidus and bony
      skull defects. Patients usually complained of exophthalmos and orbital masses. B
      scan and color Doppler showed soft tissue masses in the orbit. CT showed soft
      tissue masses and bony skull defects. MRI showed orbital tumor and intracranial
      involvement. CONCLUSIONS: Characteristic imaging features are helpful for the
      diagnosis of orbital Langerhans cell histiocytosis. The treatment includes
      surgical excision, local radiotherapy or chemotherapy. The prognosis is related
      to the types of lesion, eosinophilic granuloma shows the best prognosis and
      infantile Hand-Schueller-Christian disease shows the worst prognosis.

PMID- 17217782
TI  - [Distribution and morphological changes of corneal nerves in type 2 diabetic
      patients detected by confocal microscopy].
AB  - OBJECTIVE: To evaluate corneal nerve distribution and morphological changes in
      subjects with type 2 diabetes. METHODS: Sixty-five eyes of 59 patients with type
      2 diabetes (26 males, 39 females) and 26 eyes (10 males, 16 females) of control
      subjects were included in the present study. Based on the indirect
      ophthalmoscopic examination and fluorescein angiography, the diabetic group was
      divided into three sub-groups according to the stage of retinopathy: without
      diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR) and
      proliferative diabetic retinopathy (PDR). The central cornea was scanned with
      Confoscan 3.0. The images of subbasal nerve plexus and stromal nerves were
      analyzed. RESULTS: Corneal branch nerve fiber density of subbasal nerve plexus
      decreased in diabetic group as compared with control group, the difference was
      statistically significant. The decrease of nerve fiber density appeared only in
      the PDR sub-group, while the decrease was not significant in NDR and NPDR sub
      groups. No obviously difference was found among control group, NDR and NPDR sub
      groups. The proportion of patients with an abnormal morphologic nerve fibers in
      mid-stroma in diabetes group was greater than that in the control group and the
      difference was statistically significant (chi(2) = 46.613, P = 0.000).
      CONCLUSIONS: Corneal confocal microscope allows rapid and noninvasive in vivo
      evaluation of corneal nerves. The subbasal and stromal nerves of subjects with
      type 2 diabetes were abnormal in morphology.

PMID- 17217784
TI  - [A comparison study for differentiation between human fetal retinal progenitor
      cells and brain neural stem cells in vitro].
AB  - OBJECTIVE: Investigating the potential of differentiation of human fetal retinal
      progenitor cells (hRPCs) and brain neural stem cells (hBNSCs) in vitro. METHODS:
      hRPCs and hBNSCs were isolated from human fetuses (8-12 weeks of gestation) and
      cultured in serum-free DMEM/F12 culture medium with N2 supplement, epidermal
      growth factor (EGF) and basic fibroblast growth factor (bFGF) or culture medium
      with 10% fetal bovine serum (FBS) but without EGF and bFGF. Immunocytochemical
      and immunofluorescence studies were conducted for identification of neural stem
      cells, retinal progenitors or the subtypes of neurons, astrocytes, retinal
      ganglion cells and rod photoreceptors with the specific antibodies for Nestin,
      Pax6, Map2, GFAP, Thy-1 and Rhodopsin, respectively. RESULTS: Both hRPCs and
      hBNSCs could proliferate and differentiate in DMEM/F12 + N2 with or without 10%
      FBS and expressed specific markers of immature neuroepithelial cells, retinal
      progenitors, mature neurons, astrocytes, retinal ganglion cells and rod
      photoreceptors. hBNSCs easily attached, spread out longer neurites and to form a
      network when cultured with serum contained medium. hRPCs were more difficult to
      attach and had only short dendrites. CONCLUSIONS: Both hRPCs and hBNSCs can
      differentiate into retinal specific cell types in vitro. The adherent, migration
      and differential capacity of hRPCs and hBNSCs are different when these cells are
      induced by the serum-contained culture medium.

PMID- 17217785
TI  - [Mapping of a pedigree with autosomal dominant inherited congenital sutural
      cataract].
AB  - OBJECTIVE: To map the gene responsible for autosomal dominant congenital sutural
      cataract of a Chinese family. METHODS: Peripheral blood samples were collected
      from the members in a family with autosomal dominant congenital sutural cataract.
      The genomic DNA was extracted from the blood samples. A genescan was performed
      using approximately 400 microsatellite markers (ABI). Linkage analysis was
      processed by Linkage software package to define the location of mutation gene.
      High density primers labeled with fluorescent stain for the positive region were
      adopted for fine targeting, and haplotype analysis was processed using Cyrillic
      software. RESULTS: The maximum two-point LOD scores was obtained at D3S1279,
      Z(max) = 2.32 (theta(max) = 0.00). After fine targeting and haplotype analysis,
      the gene was located within a 38.6 cM region between D3S1267 and D3S1614.
      CONCLUSION: The gene responsible for congenital sutural cataract in a Chinese
      pedigree is located at chromosome 3q21.1 - q26.2 within a 38.6 cM region.

PMID- 17217786
TI  - [Autosomal dominant congenital golden crystal nuclear cataract caused by a
      missense mutation in gammaD crystallin gene (CRYGD) in a Chinese family].
AB  - OBJECTIVE: To identify genetic defects associated with autosomal dominant
      congenital golden crystal nuclear cataract (ADCC) in a Chinese pedigree of
      northern China. METHODS: Clinical data were collected and the lens changes of the
      affected members in this family were recorded by slit lamp photography. Genomic
      DNA was obtained from blood leucocytes. Linkage analyses was conducted using
      polymorphisms of 21 microsatellite markers and mutational analyses of candidate
      genes was studied by direct sequencing. RESULTS: The maximum LOD score (1.505 at
      recombination fraction theta = 0.00) was obtained at markers D2S1782, D2S1384 and
      D2S1385 near the gamma-crystallin gene (CRYG) cluster within 2q33 - q35.
      Sequencing analysis of the coding regions of the CRYGA. B, C, and D genes showed
      that the there was a heterozygous C-->A transversion at position 109 (R36S) in
      exon 2 of CRYGD gene, which was co-segregated with the affected members.
      CONCLUSIONS: R36S mutation in CRYGD gene results in an ADCC phenotype that is
      different from previous reports. This finding indicates that the presence of
      phenotypic heterogeneity of cataract, especially in different races. This is the
      first report of congenital cataract caused by R36S mutation in CRYGD gene.

PMID- 17217787
TI  - [The role of connective tissue growth factor, transforming growth factor and Smad
      signaling pathway during corneal wound healing].
AB  - OBJECTIVE: To study the expression and location of connective tissue growth
      factor (CTGF) and transforming growth factor-beta(1) (TGF-beta(1)) protein and
      mRNA in rabbit cornea during the wound healing process. To assess the interaction
      between CTGF and TGF-beta(1), as well as the Smad signaling pathway involved.
      METHODS: Twenty-six Albino white rabbits were used as experimental animals and
      randomly divided into 4 groups: (1) CONTROL GROUP: two rabbits. (2) Simple
      corneal injury group: a 3 mm diameter and 0.05 mm depth corneal tissue was
      excised by a trephine at the anterior central cornea as a corneal wound model in
      12 rabbits. Two rabbits were randomly sacrificed at 2 h, 6 h, 1 d, 3 d, 7 d and
      21 d after the trauma. (3) TGF-beta(1) antibodies treated group: 6 rabbits were
      injected with TGF-beta(1) antibodies (15.5 microg) subconjunctivally after
      corneal trephine. Two rabbits were randomly sacrificed at 3 d, 7 d and 21 d after
      the injection. (4) Smad4 antibodies treated group: 6 rabbits were injected with
      Smad4 antibodies (20 microg) subconjunctivally after corneal trephine. Two
      rabbits were randomly sacrificed at 3 d, 7 d and 21 d after the injection.
      Protein of CTGF, TGF-beta(1), and FN was assessed with immunohistochemistry. CTGF
      and type one collagen mRNA were measured in by in situ hybridization. RESULTS:
      (1) CTGF protein or mRNA did not exist in normal rabbit corneas, but TGF-beta(1)
      protein was expressed in normal rabbit cornea epithelium. (2) Cornea fibroblasts
      activated 6 h after the operation. Expression of CTGF, TGF-beta(1), FN protein
      and mRNA of CTGF and type one collagen were upregulated after cornea injury, and
      reached the highest level in 3 days. The expression was reduced to the basal
      level 21 days later. (3) Injection of TGF-beta(1) antibodies reduced the
      expression of CTGF, TGF-beta(1) and FN in the cornea stroma and down-regulated
      the expression of CTGF in corneal epithelial cells. (4) Injection of Smad4
      antibodies inhibited the expression of TGF in the stroma but did not change the
      expression of CTGF. CONCLUSIONS: Injury can upregulate the expression of CTGF,
      TGF-beta(1), FN and type one collagen proteins and mRNA of CTGF and TGF-beta(1).
      TGF-beta(1) and CTGF affect the wound healing process. TGF can induce the
      activation of corneal fibroblasts and upregulate the expression of CTGF. CTGF
      modulates the production of FN and Type one collagen. These data support the
      hypothesis that TGF-beta(1) and CTGF promote cornea scar formation and imply that
      the regulation of CTGF and TGF-beta(1) synthesis may be a therapy target for
      reducing corneal scarring.

PMID- 17217788
TI  - [Amniotic membrane as a carrier for cultivated and labeled corneal endothelial
      cell transplantation].
AB  - OBJECTIVE: To investigate the feasibility of using amniotic membrane (AM) as a
      carrier for cultured corneal endothelial cells transplantation. METHODS: Rabbit
      corneal endothelial cells were cultivated, passaged, and labeled with the
      fluorescent tracker CM-DiI, then transplanted onto denuded AM. The cell density,
      morphology, histology and ultrastructure of the cultured cells on AM were
      examined by light microscope, fluorescent microscopy and scanning electron
      microscope. To determine whether these composite endothelial sheets were
      functional in vivo, the sheets were transplanted onto rabbit corneas whose deep
      lamellar with Descemet's membrane and endothelial cells had been completely
      removed. The deep layer excised rabbit corneas without any transplantation or
      with transplantation of denuded AM were treated as controls. After
      transplantation, the corneal appearance and corneal thickness were examined. The
      grafts were examined for cell density, morphology and histology 4 weeks after the
      surgery. RESULTS: A monolayer of endothelial cells were confluent on the AM 5 - 7
      days after seeding. The density of the endothelial cells was (3202.84 +/-
      347.77)/mm(2). Morphologically, the sheets consisted of a fairly continuous layer
      of flat polygonal endothelial cells that appeared uniform in size with tight
      junctions. The labeled cells were red in color under fluorescent microscopy.
      After transplantation, the corneas that received cultured endothelial cells had
      little edema and retained their thinness and transparency, while the corneas of
      controls showed prominent edema and opacity, indicating that these cells were
      transplanted cells rather than the cells migrated from peripheral cornea. Four
      weeks after surgery, the labeled endothelial cells were still found in the cornea
      with red fluorescence. CONCLUSIONS: AM maintains cultured endothelial cells'
      morphology and function both in vitro and in vivo. AM could serve as a carrier
      for corneal endothelial cells transplantation. These results provide a promising
      method for the treatment of diseases caused by corneal endothelial disorders.

PMID- 17217810
TI  - [Application of anticoagulating medicine after surgery of cavity of pelvis and
      abdomen].

PMID- 17217811
TI  - [The radical problem of the celioscopic-assisted colonic and rectal cancer
      surgery].

PMID- 17217812
TI  - [Laparoscopic-assisted radical gastrectomy: a report of 105 cases].
AB  - OBJECTIVE: To investigate the feasibility and safety of laparoscopic-assisted
      radical gastrectomy for gastric cancer. METHODS: One hundred and five patients
      with gastric cancer received laparoscopic-assisted radical gastrectomy, radical
      total gastrectomy were performed in 7 cases, proximal gastrectomy in 27 cases,
      proximal gastrectomy combined with splenectomy in 3 cases and distal gastrectomy
      in 68 cases. RESULTS: One hundred and five cases had laparoscopic-assisted
      radical gastrectomy successfully. The mean operation time was 381 +/- 91 (300 -
      435) min for total gastrectomy, 279 +/- 73 (212 - 390) min for proximal
      gastrectomy, 312 +/- 64 (265 - 405) min for proximal gastrectomy combined with
      splenectomy, 281 +/- 69 (230 - 360) min for distal gastrectomy, respectively. The
      mean blood loss was 260 +/- 202 (20 - 900) ml in total gastrectomy, 200 +/- 153
      (20 - 400) ml in proximal gastrectomy, 333 +/- 116 (200 - 400) ml in proximal
      gastrectomy combined with splenectomy, 140 +/- 82 (20 - 450) ml in distal
      gastrectomy, respectively. The mean number of harvested lymph nodes was 34.2 +/-
      20.5 (8 - 83). The mean time for gastrointestinal function recovery was 3.5 +/-
      1.4 (2 - 5) days, 3.0 +/- 1.6 (2 - 6) days for patients' taking normal activity,
      4.9 +/- 1.7 (3 - 7) days for taking liquid food. The short-term efficiency was
      obvious. CONCLUSIONS: Laparoscopic-assisted radical gastrectomy is a feasible and
      safe surgical procedure combined with minimal trauma and fast recovery.

PMID- 17217813
TI  - [The application of selective portal inflow occlusion in laparoscopic
      hepatectomy].
AB  - OBJECTIVE: To discuss the safety and the feasibility of laparoscopic selective
      portal inflow occlusion. METHODS: From January 2005 to February 2006, 7 patients
      were performed by laparoscopic hepatectomy with selective portal inflow
      occlusion. The patients included 1 male and 6 females, the mean age was 48.9
      years, ranged from 31 to 70 years. Procedure included left lateral
      segmentectomies (4 patients), left hemihepatectomies (2 patients), and right
      hemihepatectomies (1 patient). Portal vein, hepatic artery and their branches
      were exposed by blunt dissection and performed selective portal occlusion with
      absorbable clips. RESULTS: There is no conversion, no mortality, and no
      postoperative complication. Seven selective portal inflow occlusions were
      performed successfully. The mean operating time was 188.7 min (range 70 min to
      300 min), the mean intraoperative blood loss was 625 ml (range 350 ml to 1000
      ml), and the mean postoperative hospital stay was 8.4 days. CONCLUSIONS:
      Laparoscopic selective portal inflow occlusion is a safe and feasible technique.

PMID- 17217814
TI  - [Prevalence of Val158Met polymorphism in COMT gene on non-BRCA1/2 hereditary
      breast cancer].
AB  - OBJECTIVE: To explore the prevalence of Val158Met polymorphism in Catechol-O
      methyltransferase (COMT) gene and its effect on genetic susceptibility for breast
      cancer in Shanghai population. METHODS: A total of 114 patients with BRCA1/BRCA 2
      negative hereditary breast cancer from independent families and 121 age-matched
      healthy controls were analyzed. Genotype analysis was conducted by polymerase
      chain reaction (PCR) and then DNA direct sequencing. The odd ratios (OR) and 95%
      confidence intervals (CI) were calculated by unconditional logistic regression
      model. RESULTS: The frequency of Val158Met polymorphism GG, GA and AA genotype in
      case group and control was 0.58 (65), 0.32 (36), 0.10 (11) and 0.60 (66), 0.35
      (41), 0.03 (3), respectively. The frequency of allele-containing genotypes is
      significantly higher in early-onset breast cancer patients (0.57) than in
      familial ones (0.35). Compared with GG (Val/Val) genotype, AA (Met/Met) genotype
      confers a significantly increased risk for breast cancer (adjusted OR = 3.15; 95%
      CI, 0.70 - 14.19), especially among premenopausal women (adjusted OR = 9.98; 95%
      CI, 1.00 - 99.64). Borderline significantly association was found between AA
      genotype (adjusted OR = 7.57; 95% CI, 0.57 - 101.28) and susceptibility for
      breast cancer in BMI < or = 23 kg/m(2) group. CONCLUSIONS: Val158Met polymorphism
      in COMT gene could be a candidate for low penetrance breast cancer susceptibility
      in Shanghai population, especially among premenopausal women and early-onset
      breast cancer patients.

PMID- 17217815
TI  - [Loss of heterozygosity on chromosome 3p in breast cancer and precancerous
      lesion].
AB  - OBJECTIVE: To study the loss of heterozygosity (LOH) on chromosome 3p in breast
      cancers and precancerous lesion. METHODS: LOH at 11 microsatellite loci was
      detected in 41 cases of breast cancers and 12 cases of precancerous lesion by
      polymerase chain reaction and silver stain. The expressions of ER, PR, FHIT and
      hMLH1 were detected in breast cancer by immunohistochemistry. RESULTS: LOH on 3p
      was detected in 97% of breast cancers. D3S1295, D3S1029 and D3S1038 located at
      3p14, 3p21-p22 and 3p25 were identified as the loci with most frequent LOH
      (53.1%, 43.6% and 52.5%). LOH of D3S1038 and expression of hMLH1 protein
      correlated with several clinicopathological features. LOH of D3S1295 had
      significant negative correlation with the expression of FHIT. In breast
      precancerous lesions, LOH on 3p was detected in 41.7% lesions. D3S1295 and
      D3S1029 were also identified as the most frequent LOH locus (27.3% and 16.7%).
      The smallest common LOH region seems likely lie between 3p14 and 3p25.
      CONCLUSIONS: The smallest LOH region indicates the existence of breast tumor
      related genes and some of them affect gene expression.

PMID- 17217816
TI  - [Clinicopathological significance of aromatase expression in breast cancers].
AB  - OBJECTIVE: To study the effects of aromatase on breast cancer proliferation and
      invasive ability, so as to detect the relationship between in situ estrogen
      levels and molecular biological characteristics of breast cancer. METHODS: By
      immunohistochemistry staining, the expression of aromatase, matrix
      metalloproteinases 2 (MMP2) and matrix metalloproteinases (MMP 9) in the primary
      breast cancers were detected, the associations between aromatase and MMPs as well
      as clinical-pathological factors were analyzed. RESULTS: The positive rates of
      aromatase were 25.0% (+) and 29.9% (++). Aromatase status was associated with
      MMP2, MMP9 and co-expression of MMP2 and MMP9 (P < 0.05), but not associated with
      tumor size, ER/PR status, menopausal status and tumor grade (P > 0.05). In the
      postmenopausal patients there was a relationship between aromatase and tumor size
      (P < 0.05), but not in the premenopausal patients (P > 0.05); there was a
      relationship between aromatase and co-expression of MMP2/MMP9 in the patients
      with ER and/or PR positive (P < 0.05), but not in the patients with ER and PR
      negative (P > 0.05). CONCLUSIONS: In the breast cancer in situ estrogen produced
      by tumor aromatase may promote the cancer cells proliferation and invasiveness
      and maybe through ER pathway especially in the postmenopausal patients.

PMID- 17217817
TI  - [Stereotactic biopsy for non-palpable breast lesions: evaluation and choice of
      minimal invasive and excisional biopsy].
AB  - OBJECTIVE: To evaluate three biopsy methods which are currently used in
      stereotactic breast biopsy. METHODS: A total of 361 cases of stereotactic breast
      biopsies were carried out since 2000, including 73 cases of true cut core needle
      biopsies (ST-CNB), 74 cases of vacuum assisted biopsies (ST-VAB) and 214 cases of
      excisional biopsies. After medium follow-up time of 18 months (6 to 66 months),
      the accuracy as well as the clinical benefits of the three stereotactic biopsy
      procedures were analyzed retrospectively. RESULTS: The cancer miss rate of
      stereotactic wire localized excisional biopsy, ST-CNB and ST-VAB is 0, 2.7% and 0
      respectively. Under-estimate rate of minimal invasive biopsy was 33% in atypical
      ductal hyperplasia (ADH) and 53% in ductal carcinoma in situ (DCIS). The minimal
      invasive procedure is superior to surgical procedure in terms of operation time,
      breast cosmetic outcome and complications, etc. Furthermore, 69% of the surgeries
      for suspicious lesion were waived. CONCLUSIONS: Stereotactic minimal invasive
      breast biopsy, especially ST-VAB, is an accurate, safty and convenient diagnosis
      technique and could be considered as the first line choice for mammographic
      moderate suspicious breast lesions (BIRADS-4). However, further excisional biopsy
      is recommended for atypical hyperplasia. Stereotactic excisional biopsy could be
      directly used for diagnosis of mammographic highly suspicious breast lesions
      (BIRADS-5).

PMID- 17217818
TI  - [One-day bowel preparation with sodium phosphate prior to colorectal surgery: a
      prospective, randomized, controlled clinical trial].
AB  - OBJECTIVES: To investigate the feasibility and safety of one-day bowel
      preparation for colorectal surgery. METHODS: Forty patients undergone colorectal
      surgery were divided randomly into the Control group and the Experimental group
      and received 3-day magnesium sulfate and 1-day sodium phosphate bowel
      preparations before the operation, respectively. The levels of hemoglobin,
      hematocrit, serum electrolytes, and anaerobe counts in the stool prior and post
      bowel preparation were examined. The general status, surgical complications, and
      structure of intestinal mucosa in the patients were observed after the operation.
      RESULTS: There was no significant difference in the anastomoses healing,
      infectious complications, serum tests and intestinal mucosa structures between
      the two groups. Less diarrhea occurred prior and post the surgery in the
      experimental group, and they felt better with the bowel preparation. The anaerobe
      counts in stool were higher after the bowel preparation than before in both
      groups. CONCLUSIONS: One-day bowel preparation with sodium phosphate is a safe
      and reliable method for colorectal surgery. The shortening of preparation time
      can reduce the degrees of uncomfortable feeling and disruptions of intestinal
      micro-ecology and barrier.

PMID- 17217819
TI  - [Therapeutic effect of excision of hypomere esophagus and proximal stomach on
      portal hypertension and upper gastrointestinal bleeding].
AB  - OBJECTIVE: To analyze the therapeutic effect of excision of hypomere esophagus
      and proximal stomach (Phemister operation) on portal hypertension and upper
      gastrointestinal bleeding. METHODS: Retrospectively analyze the clinical data of
      136 cases treated with the Phemister operation for portal hypertension and upper
      gastrointestinal bleeding from August 1999 to May 2005. RESULTS: Varication of
      the patients improved markedly, 50.8% of the varication disappeared completely,
      incidence of complications was 5.0%, rebleeding rate was 4.4%, mortality rate was
      0.7%. CONCLUSIONS: The Phemister operation could treat the upper gastrointestinal
      bleeding and prevent rebleeding effectively in portal hypertension, it is a
      radical, precise and secure disconnection for portal hypertension with varication
      in fundus of stomach and esophagus.

PMID- 17217820
TI  - [Risk factors for postoperative gastroparesis syndrome after
      pancreaticoduodenectomy with binary logistic regression].
AB  - OBJECTIVE: To study the risk factors of postoperative gastroparesis syndrome
      after pancreaticoduodenectomy. METHOD: Clinical data of 166 patients who
      underwent pancreaticoduodenectomy from January 2002 to April 2006 were analyzed
      with binary logistic regression in order to explore the risk factors of
      postoperative gastroparesis syndrome after pancreaticoduodenectomy. RESULTS:
      There were 60 patients occurred postoperative gastroparesis syndrome after
      pancreaticoduodenectomy. Among 15 factors, 6 factors were proved to be the risk
      factors of postoperative gastroparesis syndrome after pancreaticoduodenectomy by
      unitary anylasis; 7 factors were proved related factors of postoperative
      gastroparesis syndrome after pancreaticoduodenectomy by analyzed with binary
      logistic regression. CONCLUSIONS: The risk factors are preoperative gastro
      intestinal obstruction syndrome, extensive lymphadenectomy, postoperative
      abdominal cavity infection, starting time of postoperative enteral nutrition,
      postoperative blood glucose level; The protective factors are preoperative
      percutaneous transhepatic cholangial drainage (PTCD) and postoperative blood
      terminal protein (TP) level.

PMID- 17217821
TI  - [The therapeutic effects of fluid resuscitation in severe sepsis and septic
      shock].
AB  - OBJECTIVE: To evaluate the therapeutic effect of fluid resuscitation on severe
      sepsis and septic shock. METHODS: Twenty patients with severe sepsis and septic
      shock were given fluid resuscitation and got the following parameters in the
      ranges as follow: central venous pressure (CVP) 8 - 12 mm Hg (for ventilation
      patient: 12 - 15 mm Hg), mean artery pressure (MAP) 65 - 90 mm Hg, mixed venous
      oxygen saturation (SmvO(2)) > 70%. Hemodynamics, tissue perfusion and vascular
      endothelial cell function were measured and compared before and after fluid
      resuscitation. RESULTS: Pulmonary arterial wedge pressure (PAWP), cardiac index
      (CI), left ventricular stroke work index (LVSWI) and systemic vascular resistance
      index (SVRI) increased significantly after reached the goal of fluid
      resuscitation (P < 0.01) whereas pulmonary vascular resistance index (PVRI),
      lactate level in arterial blood and gastric-to-arterial carbon dioxide partial
      pressure gap (Pg-aCO(2)) decreased significantly (P < 0.01), and the serum levels
      of endothelin (ET) and von Willebrand factor (vWF) were also decreased
      significantly after fluid resuscitation (P < 0.05). CONCLUSIONS: Early goal
      directed fluid resuscitation can improve hemodynamics, tissue perfusion and
      alleviate vascular endothelial cell injury in patients with severe sepsis and
      septic shock, it is an effective therapy for these patients.

PMID- 17217822
TI  - [Expression and significance of GCS gene in human pancreatic cancer cell SW1990
      and its drug-resistant sublines].
AB  - OBJECTIVE: To study the expression and significance of GCS gene in human
      pancreatic cancer cell line SW1990 and its drug-resistant sublines. METHODS:
      SW1990 and its drug-resistant sublines, SW1990/FU, SW1990/ADM and SW1990/GEM were
      cultured in vitro. CCK-8 (Cell Counting kit-8) was used to detect the drug
      resistance of the sublines. Relative quantitation of GCS mRNA expression was
      evaluated by real-time PCR and Western blot was adopted to evaluate the
      expression of GCS protein. RESULTS: The drug resistance indexes of SW1990/FU,
      SW1990/ADM and SW1990/GEM were 339.7, 11.9 and 56.6, respectively. The GCS mRNA
      and protein were expressed in all SW1990 and its drug-resistant sublines. There
      was a higher expression of GCS mRNA in all the sublines and a significant
      difference of GCS protein expression was detected in SW1990/ADM and SW1990/GEM
      compared with SW1990. CONCLUSIONS: GCS gene is expressed in SW1990 and its drug
      resistance sublines. The high expression of GCS protein in SW1990/ADM and
      SW1990/GEM might be one reason of resistance to ADM and GEM in the sublines.

PMID- 17217823
TI  - [Nuclear factor-kappaB expression in peripheral blood polymorphonuclear
      leukocytes of patients with acute pancreatitis and the preventive effectiveness
      of pyrrolidine dithiocarbamate on NF-kappaB in vitro].
AB  - OBJECTIVE: To investigate the expression of NF-kappaB in peripheral blood
      polymorphonuclear leukocyte (PMN) of acute pancreatitis (AP) and to assess the
      preventive effectiveness of pyrrolidine dithiocarbamate (PDTC) on NF-kappaB in
      vitro. METHODS: Nineteen patients and 16 healthy individuals as control were
      enrolled in this study. The expression of NF-kappaB in PMNs was determined by gel
      electrophoretic mobility shift assay (EMSA). Routine clinical examination results
      and computed tomography findings of AP were recorded in all patients. RESULTS:
      The PMNs from the patients with AP showed higher levels of NF-kappaB activities
      than those from control subjects (P < 0.01), severe acute pancreatitis (SAP)
      group showed much higher than mild acute pancreatitis (MAP) group (P < 0.05). In
      vitro, PDTC could reduce the NF-kappaB activity in PMNs of patients with AP, and
      its effectiveness at 2 mmol/L was stronger than at 1 mmol/L (P < 0.05). The PMNs
      from control subjects pretreated with 2 mmol/L PDTC before stimulation with the
      plasma from patients with SAP showed lower levels of NF-kappaB activities than
      did those untreated (P < 0.05). CONCLUSION: The NF-kappaB activation in
      peripheral blood PMNs participate in the course of acute pancreatitis and can be
      inhibited by PDTC in vitro.

PMID- 17217824
TI  - [Effect of adenovirus-mediated mutant exogenous P27kip1 gene expression on the
      chemosensitivities of cholangiocarcinoma cell line].
AB  - OBJECTIVE: To investigate the effects of mutant exogenous P27(kip1) gene on
      chemosensitivity of human cholangiocarcinoma cell line. METHODS: The recombinant
      vector was constructed and the mutant P27(kip1) gene was transfected into human
      cholangiocarcinoma cell line (QBC(939)). RT-PCR and Western blot were used to
      determine the expression of target genes. The effects of 5-fluorouracil (5-FU),
      mitomycin C (MMC) and cyclophosphamide (CTX) on the transfected cells were
      detected by assaying the apoptotic rate and growth inhibition by
      methabenzthiazuron (MTT) assay and flow cytometry (FCM). RESULTS: The mutant
      exogenous P27(kip1) gene was expressed effectively in the cells, and the
      expression enhanced the apoptosis and growth inhibition of QBC(939) inducted by 5
      FU, MMC and CTX. The ratio of growth inhibiting increased significantly from
      41.89% (5-FU), 45.59% (MMC), 38.91% (CTX) to 56.15% (5-FU), 55.65% (MMC), 51.69%
      (CTX), and apoptosis index from 13.76% +/- 3.03% (5-FU), 11.76% +/- 3.99% (MMC),
      10.46% +/- 2.10% (CTX) to 41.39% +/- 4.32% (5-FU), 35.94% +/- 2.71% (MMC), 34.46%
      +/- 2.32% (CTX) (P < 0.05). CONCLUSIONS: The exogenous P27(kip1) gene transfer
      can remarkably increase the drug sensibility of the cholangiocarcinoma cells. The
      strategy targeted to control the cell cycle may be more effective in cancer
      treatment by combination of P27(kip1) gene therapy.

PMID- 17217826
TI  - [The issue of subluxation of atlanto-axial joint].

PMID- 17217825
TI  - [Expression of Twist gene in human hepatocellular carcinoma and its
      clinicopathological significance].
AB  - OBJECTIVE: To investigate the expression and clinicopathological significance of
      transcription factor Twist in hepatocellular carcinoma (HCC), paraneoplastic and
      cirrhotic tissues. METHOD: Immunohistochemistry was used to detect the expression
      of the Twist protein in 26 cases of HCC and paraneoplastic tissue and 10 cases of
      cirrhotic tissue. Meanwhile, the Twist mRNA and its protein were detected in 10
      HCC tissues and 10 paraneoplastic tissues by RT-PCR and Western blot. And the
      expression differences and clinicopathological significances of the expression of
      Twist gene and its protein were analyzed. RESULTS: The positive rates of the
      Twist protein in HCC, paraneoplastic and cirrhotic tissues were 84.6%, 19.2 % and
      20.0 %, respectively. The positive rate of Twist in HCC was higher than that in
      paraneoplastic or cirrhosis tissues (P < 0.05). Compared with in paraneoplastic
      tissues, the mRNA and protein expression of Twist were up-regulated in HCC by
      2.52 and 2.13 times, respectively. CONCLUSION: Twist has an inappropriate
      expression in hepatocellular carcinoma and it may play an important role in the
      tumorigenesis and progression of HCC.

PMID- 17217827
TI  - [The clinical causes of the thoracic ossification of ligamentum flavum].
AB  - OBJECTIVE: To assess the different causes of thoracic ossification of the
      ligamentum flavum (TOLF). METHODS: From July 1989 to November 2005, 142 cases
      were diagnosed the TOLF, in which 121 were operated. The lesions were classified
      into three types on the basis of the clinical result: (1) In such primary group
      (Group 1, 90 cases), without incorporation disease and Ca, P and AKP was all
      normal; (2) In systemic ossified TOLF group (Group 2, 30 cases), 6 cases
      ankylosing spondylitis, 3 cases DISH, 10 cases fluorosis, 11 cases OPLL; (3) In
      local spine disease group (Group 3, 22 cases), 5 cases fracture in spine, 4 cases
      spine TB, 13 cases posterior marginal intraosseous cartilaginous node. Such
      clinical feature was analysed, moreover surveyed the thoracic kyphosis angle,
      upper thoracic kyphosis angle, lower thoracic kyphosis angle and the vertebra
      body wedge change. The effect was assessed using Epstein Scale. RESULTS: (1) In
      Group 1, the mainly type was connected type (67/90, 74%). The ossified ligamentum
      flavum was mainly located at the lower thoracic and thoracic-lumber levels. The
      local type was less. In Group 2, the mainly type was connected type (21/30, 70%).
      The local type was none. The lesions figure was the most. In Group 3, the local
      type was the most (18/22, 82%). (2) In Group 1, the ossified ligamentum flavum
      was mainly located at the upper and lower thoracic levels (225/486, 47%). In
      Group 2, mainly located at the whole thoracic, some include cervix and lumber. In
      Group 3, mainly location was related with the location of primary disease. (3) In
      group 1, the curve was normal in 81% (73/90) of cases. In Group 2, the curve was
      abnormal in 87% (26/30) of cases. In Group 3, the curve was normal in the 82%
      (18/22) of cases. CONCLUSIONS: The TOLF relates with systemic ossify disease, the
      change of load on the spine, aging and so on. It should be classified according
      to its causes.

PMID- 17217828
TI  - [The research of bone morphogenetic protein expression, CT value and mature
      degree of ossification in the thoracic ossification of ligamentum flavum].
AB  - OBJECTIVE: To investigate the correlation of pathology, bone morphogentic protein
      (BMP) expression, CT value with the ossification of thoracic ligamentum flavum
      (TOLF) to afford the evidence to choose appropriate treatment methods. METHODS:
      Twenty-three patients aged 35 - 65 years old had TOLF in my hospital as case.
      Their courses of disease were 2 months to 9 years. The values of blood calcium,
      blood phosphorus and AKP in them were normal. The 5 peoples aged 21 - 35 years
      old who presented fracture of thoracic but not the ligamentum flavum ossification
      were selected as control. We excluded those who have DISH, ankylosing
      spondylitis, fluorosis and other disease related with TOLF. The lesion locus were
      scanned and mensurated by CT. The pathology characteristics were classified into
      immature ossification and mature ossification by general observation, histology
      examination. BMP were measured by the immunohistochemical (IHC) staining
      techniques. RESULTS: The CT value was significantly higher in the case group
      (547.2 +/- 131.4) than controlled group (137.7 +/- 10.6) (t = 6.922, P = 0.000).
      Further, the CT value in the mature ossification (702.9 +/- 17.7) was
      significantly higher than the immature (480.5 +/- 180.2) (t = 5.623, P = 0.000).
      In addition, BMP both expressed negative in the mature ossification and the
      controlled group, but positive in the immature ossification. BMP expression was
      significantly different between the immature ossification and the mature (chi2 =
      70.000, P = 0.000). CONCLUSIONS: The CT values, pathological types and BMP
      expression results are similar to evaluate the ossification degrees of ligamentum
      flavum, and then could be indirectly judged the maturation degrees of TOLF by CT
      to confirm the treatment methods before operation.

PMID- 17217829
TI  - [Variation of the position of the conus medullaris in adolescent idiopathic
      scoliosis patients with a Cobb angle greater than 40 degrees: Analysis of MRI].
AB  - OBJECTIVE: To investigate the position of the conus medullaris in adolescent
      idioppathic scoliosis (AIS) with a greater curve and the relationship of that
      with age, sex, curve severity and curve pattern. METHODS: In this study, 202 AIS
      patients with a Cobb angle greater than 40 degrees on coronal plane were
      included. And 52 age-matched healthy adolescents were recruited to serve as
      controls. Both of them displayed neurologically normal upon physical
      examinations. The T1-weighted, sagittal, spino-echo magnetic resonance imaging
      (MRI) of lumbar spine was performed on both of AIS patients and healthy controls.
      According to a standard method described previously, the position of the conus
      medullaris relative to lumbar vertebrae and intervertebral disc space was
      measured. RESULTS: There was no significant difference in the distributions of
      the positions of the conus medullaris in AIS patients and healthy controls. In
      both groups, the mean position of the conus medullaris located at the same level,
      the lower 1/3 of L(1) (range: the middle 1/3 of T(12) to L(2 - 3) disc space). No
      significant correlations were found between the position of the conus medullaris
      and age or sex in AIS and control subjects. It was shown that the positions of
      the conus medullaris were not significantly different among AIS patients with
      different curve severity and curve patterns. CONCLUSIONS: The distribution of the
      conus location in AIS patients is shown to be ranged from the middle 1/3 of T(12)
      to L(2 - 3) disc space, with no significant difference when compared to controls.
      No significant associations are found between the conus position with curve
      severity and curve patterns, indicating the conus location might be of no
      significant relevance of research on AIS pathogenesis and curve progression.

PMID- 17217830
TI  - [The clinical study of cervical arthroplasty in management of cervical
      spondylosis].
AB  - OBJECTIVE: To investigate the clinical effects of cervical disc prosthesis in
      patients of cervical spondylosis early, compared with the anterior cervical
      interbody fusion. METHODS: Bryan disc prosthesis replacement applied in 21 case
      (22 levels) of cervical spondylosis, 27 patients (32 levels) were treated by the
      anterior interbody fusion. Clinic (JOA grade) and radiological (X-ray of bending,
      extending; left and right bending position) follow-up of 48 patients was
      performed preoperatively and postoperatively. Systemic radiographic study about
      stability and rang of movement (ROM) of replaced levels postoperatively was
      measured; meantime the ROM of adjacent levels of all cases was observed. CT or
      MRI scan were applied in 21 patients postoperatively to find out the pressure of
      the spine and heterotopic ossification in the replaced level. RESULTS: There was
      no complication. Improvement in all case increased obviously, JOA score increased
      and stabilized postoperatively in all cases (P < 0.01). Replaced segment achieved
      stability and restored partial of ROM. There was no prosthesis subsidence or
      excursion. The adjacent ROM of the case treated by the anterior interbody fusion
      increased obviously (P < 0.01). No heterotopic ossification was found in the
      replaced level, but the deteriorated adjacent level of 1 case applied by the
      anterior interbody fusion occurred. CONCLUSIONS: Bryan cervical disc prosthesis
      restore stability and partial motion to the level of the intact segment in
      flexion-extension and lateral bending in postoperational images; The adjacent ROM
      has not increased obviously. At the same time, it can achieve good short-term
      clinic effect in replaced level, compared with the anterior interbody fusion.

PMID- 17217831
TI  - [Diagnosis and treatment of odontoid fracture combined with lower cervical spinal
      injury].
AB  - OBJECTIVE: To investigate the mechanism, clinical features and treatment of
      odontoid fracture combined with lower cervical spinal injury. METHODS: From
      January 1999 to December 2004, 57 cases of type II or shallow type III odontoid
      fractures were studied retrospectively. Six cases were found combined with lower
      cervical injury, the mean age was 54 years, and 4 of the 6 cases were complicated
      with cervical spondylarthrosis or ankylosing spondylitis. For the lower cervical
      injury, fracture-dislocation was found in 2 cases, the disruption of disc and
      ligament was found in 4 cases among which 2 cases were suffered from incomplete
      spinal cord injury; Both were caused by lower cervical spinal injury. All of the
      6 cases were performed with surgery in odontoid fracture and lower cervical
      spinal injury simultaneously; Lower cervical spinal injuries were stabilized
      firstly in 2 cases, which responsible for neurological involvement; For the other
      4 cases without neurological involvement, stabilization was performed in odontoid
      fracture firstly in 2 cases, due to inability to achieve reduction of odontoid
      fracture preoperatively, however, for the another 2 cases with anatomic reduction
      of the odontoid fracture preoperatively, lower cervical injuries were stabilized
      firstly. RESULTS: After an average follow-up of 10 months, all cases were
      obtained solid fusion both in odontoid fracture and lower cervical spinal injury,
      and without the complications associated with operation and prolonged bed rest.
      Two cases with neurological defect improved 1 scale in Frankel score.
      CONCLUSIONS: The incidence of odontoid fracture combined with lower cervical
      spinal injury is about 10.5% of the odontoid fracture, and it is vulnerable in
      the elderly patient with cervical spondylarthrosis. MRI should be used routinely
      for accurate diagnosis. Surgical stabilization is the choice of treatment due to
      facilitating early rehabilitation and reducing the complications. The surgical
      schedule is planned according to the fact of neurological involvement and the
      extent of stability between the odontoid fracture and lower cervical spinal
      injury.

PMID- 17217832
TI  - [Clinical contrast of cervical pedicle screw fixation assisted by C-arm
      fluoroscopy or 3D navigation system].
AB  - OBJECTIVE: To evaluate the feasibility and accuracy of cervical (C(2)-C(7))
      pedicle screw fixation assisted by C-arm fluoroscopy or 3D navigation system (CT
      based navigation system or Iso-C 3D navigation system). METHODS: One hundred and
      forty-five cervical pedicle screws inserted with C-arm fluoroscopy and 187
      pedicle screws inserted with 3D navigation system were observed by postoperative
      CT or Iso-C 3D scan. The process of navigation was investigated. RESULTS: In the
      145 screws inserted with C-arm fluoroscopy, 133 screws are accurate (91.7%), and
      in the 187 screws inserted by 3D navigation system, 183 screws are accurate
      (97.9%) (chi2 = 6.705, P = 0.010), and the 4 misplaced screws occurred in the
      early stage of navigation system application. The process of navigation was
      investigated in twenty-five patients. With CT-based navigation, the mean time for
      registration and surface matching was 3.5 minutes; with Iso-C 3D navigation, the
      mean time for images collection and transfer was 6.2 minutes. The mean time for
      screw-marker insertion was 2 minutes. CONCLUSIONS: 3D navigation system can
      increase accuracy of cervical pedicle screw fixation obviously.

PMID- 17217833
TI  - [Total hip arthroplasty for Crowe type-IV development dysplasia of hip in
      adults].
AB  - OBJECTIVE: To determine the operation procedure of total hip arthroplasty (THA)
      for Crowe type-IV developmental dysplasia of hip and its relationship with nerve
      injury. METHODS: A consecutive series of 39 THAs was performed for Crowe type-IV
      developmental dysplasia of hip in 35 patients (all female). The mean age of the
      patients at the time of surgery was 46 years (range 36 - 56 years). Thirty-five
      hips in 31 patients were followed up. The average follow-up period of the whole
      series was 4 years (range 1 - 8 years). All procedures were carried out through a
      lateral-posterior approach. In 33 of 35 hips, the cup was inserted in the "true"
      acetabulum. All the prostheses used were cementless, except for 5 cemented
      femoral stems in 5 patients. Each patient was evaluated clinically and by
      radiographs before the operation and during the follow-up period, according to
      the Harris hip score (HHS). RESULTS: None of the cups and stems were revised for
      aseptic loosening, dislocation or infection during the follow-up period. The mean
      preoperative HHS was 43 compared with the postoperative HHS of 87. The mean
      amount of postoperative leg lengthening was 5 cm (range 4 - 6 cm). CONCLUSIONS:
      The reconstruction of the hip at the level of the "true" acetabulum through a
      lateral-posterior approach is a safe and effective procedure of THA for Crowe
      type-IV developmental dysplasia of hip in adults. Acute leg lengthening of less
      than 6 cm could not cause nerve injury.

PMID- 17217835
TI  - [Revision total hip arthroplasty for the failed hemiarthroplasty].
AB  - OBJECTIVE: To investigate the surgical indications and surgical techniques of
      revision total hip arthroplasty for the failed hemiarthroplasty. METHODS: From
      June 1997 to June 2000, 56 cases (31 males and 25 females) of failed
      hemiarthroplasty received the revision total hip arthroplasty. The age was from
      64 - 75 years (mean 68 years). Among them, there were 29 cases with acetabular
      erosion, 14 cases with acetabular erosion and central dislocation of femoral
      head, 12 cases with stem loosening and 1 case with stem fracture. All the cases
      were revised in one stage, and bone grafts were adopted when necessary. RESULTS:
      Forty-nine cases were followed up for 5 - 8 years (mean, 7 years), and 7 cases
      had lost. The mean Harris score increased from 37 (rang, 28 - 40) preoperatively
      to 88 (rang, 84 - 90) at last follow-up. No wound infection and neurovascular
      injury happened. Only 5 perioperative complications occurred, including 3 deep
      venous thrombosis, 1 dislocation and 1 cortical fracture. No cups or femoral
      stems needed re-revision. Radiographic analysis showed that the position of the
      artificial prosthesis was unchanged, and no loosening sign existed. CONCLUSIONS:
      The acetabular erosion and central dislocation of femoral head are the main
      reasons for revision total hip arthroplasty after hemiarthroplasty. The medium
      term follow-up results show that the clinical effects are encouraging if the
      surgical indications and surgical techniques are suitable.

PMID- 17217836
TI  - [Change in the joint line after total knee arthroplasty].
AB  - OBJECTIVE: To investigate the change in joint line after knee arthroplasty.
      METHODS: A total of 43 patients had 25 primary cruciate-retaining total knee
      replacements (Link Gemini MKII) and 25 rotational knee replacements (Link Endo
      Model Rotational Knee System) sacrificing collateral ligaments and cruciate
      ligaments. Lateral radiographs were made both preoperatively and postoperatively.
      The change in the relative position of the joint line preoperatively and
      postoperatively was defined as the difference between the perpendicular distance
      from the weight-bearing surface of the tibial plateau to the tibial tubercle of
      the natural tibia (JL) and perpendicular distance from the weight-bearing surface
      of the prosthetic tibial component to the tibial tubercle (JL'). This distance
      was JL'-JL. The statistical differences between 2 groups were analyzed. RESULTS:
      The distance of JL'-JL was 2.0 mm (-1.3 - 7.2 mm) in 22 patients with Gemini
      replacement, whereas the distance was 3.1 mm (-1.5 - 12.3 mm) in the other
      patients with rotational knee system. The difference was significant.
      CONCLUSIONS: If the collateral ligaments and cruciate ligaments are removed
      during the knee replacement operations, the prosthetic joint line is likely to be
      malpositioned proximally. The fibular styloid and medial or lateral epicondylar
      reference points can be used to determine proper position of the joint line
      during operation.

PMID- 17217837
TI  - [The role of CT in the diagnosis and treatment of distal radius fracture].
AB  - OBJECTIVES: To investigate and discuss the role of CT in the diagnosis and
      treatment of comminutive distal radius fractures. METHODS: One hundred and eleven
      consecutive patients (118 cases of fractures) who were admitted to Jishuitan
      hospital from January 2003 to January 2005 were included in this study. These
      patients all need operative treatment and accepted CT scans for better
      understandings of these injuries and helping to make operation plans. RESULTS:
      after comparing the results of X planes and CT scans, considerable differences
      existing between the two examinations were found in the measurements of articular
      compression and step-off, gapping, comminution degree and subdislocation. This
      difference was manifested not only in the alteration of quantity but also in the
      change of quality. CONCLUSIONS: Computed tomography can provide more vivid and
      detailed information of fractures for practitioners. Undoubtedly, CT is
      especially valuable in the evaluation of severity degree and stability of
      comminutive distal radius fractures, thus it helps us to determine whether
      operation is obligatory and choose the best method and approach of operation.
      Moreover, CT can also clearly show the important parts of fractures which need
      special attention in the process of operation. At the same time, practitioners
      are required to understand the indications of CT examination completely and know
      how to choose scan planes properly.

PMID- 17217838
TI  - [Treatment of the ununited lower limb fracture with reamed intramedullary
      interlocking nail].
AB  - OBJECTIVE: To investigate the clinical effect of the treatment of the ununited
      lower limb fracture with reamed intramedullary interlocking nail. METHODS: Fifty
      two patients with ununited lower limb fracture were treated with intramedullary
      interlocking nail (femur 36, tibia 16). The main cause of nonunion was
      interternal fixation loosening or fracture (41 cases, 78.8%), other reasons
      included bone defection, bone infection or too much traction of fracture (11
      cases, 21.2%). According to X-ray classification: 41 cases in type hypertrophy,
      11 cases in type atrophy. All these patients need operation to remove the primary
      implant, clean the hard bone, ischemia bone and scar, manual ream and fix by
      intramedullary interlocking nail, then bone graft were done around the fracture
      site. With the knee joint stiffness, relax it by manipulate or operation.
      RESULTS: Beside 3 superficial infection (2 delayed healing and 1 healing after
      debridement), other 49 wounds healed on time. All cases were followed up for an
      average of 25.2 months, ranging from 12 months to 39 months. All the ununion
      healed from 5 to 11 months, mean union time were 6.1 months. Deep tissue
      infection, fat embolism, implant loosening, nail broken or nonunion were not
      found in this series. According to judet standard on the movement of knee, the
      excellent-good rate was 82.7%. CONCLUSIONS: Intramedullary interlocking nail is
      effective to treat nonunion of lower limb fracture.

PMID- 17217840
TI  - [Distribution and expression of collagen type II, transforming growth factor
      beta1 and basic fibroblast growth factor in articular process cartilages of
      scoliosis].
AB  - OBJECTIVE: To look into the character of the expression of collagen type II and
      transforming growth factor beta1 (TGF-beta1), basic fibroblast growth factor
      (bFGF) in the apical articular process cartilages of adolescent idiopathic
      scoliosis (AIS) and congenital scoliosis (CS) patients. METHODS: The articular
      processes of 22 AIS and 18 CS were collected. The techniques of HE staining,
      immunohistochemistry and in situ hybridization were adopted in this research. By
      comparing the apical processes with the end processes, the convex processes with
      the concave processes, the AIS processes with CS processes, the pathological
      changes of the articular process cartilages of these patients and the
      distribution of collagen type II and TGF-beta1, bFGF in them were studied. The
      images of immunohistochemistry and in situ hybridization were input into the
      image analysis system and were analyzed semi-quantitatively. The SAS software
      (8.01) was adopted, and P < 0.05 was defined as the significant level. RESULTS:
      The expression of collagen type II and TGF-beta1, bFGF in AIS was similar to CS:
      the concave sides of apexes were higher than the convex sides. The comparisons
      had statistical significance. There was no statistical significance between upper
      and lower end vertebrae in convex and concave sides, between convex and concave
      sides in upper and lower end vertebrae. The apical vertebrae were significantly
      higher than the ipsilateral sides of upper or lower end vertebrae for collagen
      type II. There was no statistical difference of the expression at the concave,
      convex, upper, lower end vertebrae between AIS and CS. CONCLUSIONS: The
      cartilages of the apical processes show some signs of regression and hypoplasia
      in scoliosis. The concave side is more severe than the convex side. Increase of
      collagen type II and TGF-beta1, bFGF in the concave sides of apical processes in
      scoliosis may be the results of reconstruction of extracellular matrix and the
      compensation reactions which are caused by abnormal biomechanical forces such as
      compressive stresses. Compressive stress on the concave sides has more influences
      on the expression of collagen type II than tensile stress on the convex sides.

PMID- 17217841
TI  - [Cadaveric study of the anatomical relationship between the greater tuberosity
      and prosthetic fin in humeral head replacement].
AB  - OBJECTIVE: To investigate the relationship of the greater tuberosity and the
      lateral fin of the prosthesis by using cadaveric research. METHODS: Nine pairs of
      fresh-frozen upper extremity specimens (n = 18) were collected. Two-part
      anatomical neck fracture models were created by osteotomy along the anatomical
      neck. A standardized humeral head replacement procedure was carried out. The
      prosthesis was implanted in 20 degrees and 40 degrees of retroversion
      respectively, and the distance between the bicipital groove and lateral fin of
      the prosthesis was measured. RESULTS: The lateral fins of prostheses in all
      specimens were located behind the bicipital groove. The average distances were
      7.3 mm in 20 degrees retroversion and 4.0 mm in 40 degrees retroversion.
      CONCLUSION: It is better to fix the greater tuberosity over the lateral fin
      during humeral head replacement.

PMID- 17217842
TI  - [Biomechanical study of four-bundle semitendinosus tendon autograft used for
      anterior cruciate ligament reconstruction in rabbits model].
AB  - OBJECTIVE: To observe the biomechanical change of the remodeling process of a
      four bundles model using semitendinosus tendon for the reconstruction of anterior
      cruciate ligament (ACL) in rabbits, and to explore the possibility of using
      braiding technique for improving the outcome for reconstruction of ACL. METHODS:
      Two techniques were employed for the ACL reconstruction, one group with the
      implant of parallel bundles and the other with the braided bundles. Specimen were
      collected at 26 and 52 weeks after surgery respectively for biomechanical test.
      Gross morphology was also observed. RESULTS: The group with the implant of the
      braided bundles showed a more fused rate. The biomechanical test showed that the
      strength of the reconstructed ACL with the unbraided bundles was 35.87% of the
      controlled normal ACL, while the braided bundles reached 67.20%. The strength of
      the graft of the 26 and 52 weeks with the braided bundles were significantly
      higher than that of the unbraided group, while the stiffness of the 52 weeks
      graft of the braided group was significantly higher than that of the unbraided
      group also. CONCLUSIONS: Braiding each bundle to become a single implant for
      reconstruction of ACL might have better outcome since it will decrease the
      movement between each bundles and improve the biomechanical properties.

PMID- 17217847
TI  - Aspirin plus dipyridamole versus aspirin alone after cerebral ischemia of
      arterial origin.

PMID- 17217848
TI  - Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation.

PMID- 17217849
TI  - Role of transcranial Doppler ultrasonography in evaluation of patients with
      cerebrovascular disease.
AB  - Transcranial Doppler ultrasonography (TCD) is the only noninvasive examination
      method that enables the reliable evaluation of blood flow from the basal
      intracerebral vessels, adding physiologic information to the anatomic images. TCD
      is relatively inexpensive, can be performed at bedside, and allows monitoring in
      acute emergency settings and for prolonged periods with a high temporal
      resolution, making it ideal for studying dynamic cerebrovascular responses. In
      acute stroke, TCD is capable of providing rapid information about the hemodynamic
      status of the cerebral circulation and monitoring recanalization in real-time,
      with a potential for enhancing tissue plasminogen activator-induced thrombolysis.
      Extended applications such as emboli monitoring, right-to-left shunt detection,
      and vasomotor reactivity make TCD an important and valuable tool for evaluating
      stroke mechanisms, planning and monitoring treatment, and determining prognosis.

PMID- 17217850
TI  - Mechanical interventions to treat acute stroke.
AB  - The approach to stroke therapy has historically been limited due to the existence
      of relatively few treatment options and the necessity for action within 3 hours
      of symptom onset. As neuroimaging technology advances, fertile new ground is
      revealed for novel therapies. Recently, a number of exciting mechanical systems
      have been developed with potential efficacy even hours after cerebrovascular
      occlusion: endovascular clot disruption, endovascular clot extraction, and
      angioplasty with stenting are currently under study, with promising initial
      results. With more options, each with greater effectiveness in a particular
      clinical scenario, the physician is now better equipped than ever to treat acute
      ischemic stroke successfully.

PMID- 17217851
TI  - Treatment of arteriovenous malformations of the brain.
AB  - The treatment of ruptured and unruptured brain arteriovenous malformations (AVMs)
      is driven by the need to prevent incident or recurrent intracranial hemorrhages.
      Improving feasibility of the rapidly developing endovascular, neurosurgical, and
      radiotherapeutic procedures leads to invasive treatment of an increasing number
      of neurologically intact patients with accidentally diagnosed AVMs. Recent data
      confirm that the natural history risk of unruptured AVMs is significantly lower
      than the risk of those presenting with rupture, and the treatment risk of
      invasive management of unruptured AVMs seems higher than their natural history
      risk. The treatment decision algorithm for these patients remains unsettled, as
      no randomized clinical trial data exist on the benefit of invasive AVM treatment
      for patients with bled or with unbled AVMs. The recently launched study A
      Randomized Trial of Unruptured Brain AVMs (ARUBA) will be the first trial
      randomizing patients with nonhemorrhaged AVMs to invasive versus conservative
      management.

PMID- 17217852
TI  - Translational research in stroke: taking advances in the pathophysiology and
      treatment of stroke from the experimental setting to clinical trials.
AB  - Many advances have occurred regarding an increased understanding of the basic
      pathophysiology of ischemic brain injury that could lead to enhanced therapy for
      this disorder. Among the more important basic science advances are enhanced
      knowledge of the components of the ischemic cascade, the phenomenon of ischemic
      preconditioning, the potential relevance of hibernation, studies on gene
      expression in ischemic tissue, and imaging identification of the ischemic
      penumbra. The large number of unsuccessful prior clinical trials with a wide
      range of purported acute stroke therapies has provided many insights and lessons
      regarding how to perform better trials in the future. Translating these basic
      science and clinical trial design advances into effective and safe therapies will
      require increased interaction and cooperation between basic scientists and
      clinical researchers.

PMID- 17217853
TI  - Intensive management of risk factors for accelerated atherosclerosis: the role of
      multiple interventions.
AB  - Patients at high risk of vascular events can reduce their risk by 75% to 80%
      through a combination of lifestyle changes and medical therapy. These include
      smoking cessation, a Mediterranean diet, daily exercise, maintaining a fit
      weight, moderate consumption of alcohol, effective control of blood pressure and
      diabetes, intensive treatment with lipid-lowering drugs and antiplatelet agents,
      and perhaps treatment with vitamins to lower homocysteine. Much of this is
      achieved primarily by the patient; physicians need to become better at assisting
      their patients in making lifestyle changes. Effective control of treatment
      resistant hypertension can be improved by individualizing medical therapy to the
      underlying cause, based on measurement of plasma renin and aldosterone.
      Measurement of carotid plaque may be useful by providing feedback on the success
      of therapy.

PMID- 17217854
TI  - Treatment of carotid artery disease: stenting or surgery.
AB  - Carotid endarterectomy (CEA) is the only form of cerebral revascularization for
      which Level 1 evidence of effectiveness has been reported. Recent studies
      demonstrate the feasibility of carotid artery stenting (CAS) as an alternative to
      CEA. Its popularity is due to the perceived advantages of a less invasive
      treatment for carotid occlusive disease. Two randomized trials have reported no
      difference in the composite stroke, death, and myocardial infarction rate between
      CAS and CEA. However, these trials were not powered to identify superiority
      between the two procedures. A trial sponsored by the National Institutes of
      Health is currently underway to make that determination. The lead-in phase of
      this trial noted low complication rates with CAS. These results have encouraged
      the US Food and Drug Administration to approve the use of CAS in patients with
      neurologic symptoms (ie, ipsilateral stroke, transient ischemic attacks, and
      amaurosis fugax) in association with severe medical co-morbidities. Patients with
      carotid restenosis after previous CEA, anatomically inaccessible lesions above
      C2, and radiation-induced stenoses may also benefit from preferential treatment
      with CAS. The National Institutes of Health have now expanded the Carotid
      Revascularization Endarterectomy Versus Stenting Trial (CREST) to include
      asymptomatic patients, and resulting data will help to clarify the role of CAS in
      this subset as well.

PMID- 17217855
TI  - Guillain-barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is currently divided into the two major subtypes:
      acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal
      neuropathy (AMAN). This review highlights relevant recent publications,
      particularly on the pathophysiology of AMAN. Molecular mimicry of the bacterial
      lipo-oligosaccharide by the human gangliosides is now considered an important
      cause of AMAN. Gangliosides GM1, GM1b, GD1a, and GalNAc-GD1a expressed on the
      motor axolemma are likely to be the epitopes for antibodies in AMAN. At the nodes
      or paranodes, deposition of antiganglioside antibodies initially cause reversible
      conduction block followed by axonal degeneration. Electrodiagnostic findings
      support this process. Disruption of glycolipids, which are important to maintain
      ion channel clustering at the nodes and paranode, may impair nerve conduction.
      Genetic polymorphisms of Campylobacter jejuni determine the expression of the
      gangliosides on the bacterial wall. In contrast, target molecules in AIDP have
      not yet been identified. Meta-analyses show efficacy of plasmapheresis and
      immunoglobulin therapy, but not corticosteroids, in hastening recovery.

PMID- 17217856
TI  - Chronic inflammatory demyelinating polyneuropathies: current treatment
      strategies.
AB  - Chronic inflammatory demyelinating polyradiculopathy (CIDP), considered an immune
      mediated disease, is likely under-recognized and under-treated due to its
      heterogeneous presentation and the limitations of clinical, serologic, and
      electrophysiologic diagnostic criteria. Despite these limitations, early
      diagnosis and treatment is important in preventing irreversible axonal loss and
      improving functional recovery. Primary treatment modalities include intravenous
      immunoglobulin and plasmapheresis, for which there is randomized, double-blind,
      placebo-controlled evidence. In addition, despite less definitive published
      evidence of efficacy, corticosteroids are considered standard therapies because
      of their long history of use. Studies have failed to demonstrate a difference in
      efficacy among these three treatments; consequently, the choice is usually based
      on availability and side-effect profile. A number of chemotherapeutic and
      immunosuppressive agents have also shown to be effective in treating CIDP but
      significant evidence is lacking; therefore, these agents are primarily used in
      conjunction with other modalities. Regardless of the treatment choice, long-term
      therapy is required to maintain a response and prevent relapse.

PMID- 17217857
TI  - Acid alpha-glucosidase deficiency (Pompe disease).
AB  - The development and recent approval of recombinant acid alpha-glucosidase for
      enzyme replacement therapy have been major milestones in Pompe disease research.
      Acid alpha-glucosidase is the enzyme responsible for degradation of glycogen
      polymers to glucose in the acidic milieu of the lysosomes. Cardiac and skeletal
      muscles are the two major tissues affected by the accumulation of glycogen within
      the lysosomes. Both cardiomyopathy and skeletal muscle myopathy are observed in
      patients with complete enzyme deficiency; this form of the disease is fatal
      within the first year of life. Skeletal muscle myopathy eventually leading to
      respiratory insufficiency is the predominant manifestation of partial enzyme
      deficiency. The recombinant enzyme alglucosidase alfa is the first drug ever
      approved for this devastating disorder. This review discusses the benefits and
      the shortcomings of the new therapy.

PMID- 17217858
TI  - Emery-Dreifuss muscular dystrophy.
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is inherited in an X-linked or autosomal
      manner. X-linked EDMD is caused by mutations in EMD, which encodes an integral
      protein of the nuclear envelope inner membrane called emerin. Autosomally
      inherited EDMD is caused by mutations in LMNA, which encodes A-type nuclear
      lamins, intermediate filament proteins associated with inner nuclear membrane.
      Although the causative mutations have been described and mouse models have been
      created, the pathogenic processes by which mutations in genes encoding nuclear
      envelope proteins cause striated muscle abnormalities in EDMD remain obscure.
      Working hypotheses include effects on nuclear structural integrity, increased
      cellular susceptibility to mechanical stress damage, alterations in gene
      expression in response to nuclear envelope changes, and effects on cell
      proliferation and differentiation.

PMID- 17217859
TI  - Molecular genetics of McArdle's disease.
AB  - This review highlights recent advances in our understanding of McArdle's disease,
      including the mechanisms involved in the regulation of the clinical phenotype.
      The latest molecular genetic studies have demonstrated the genetic heterogeneity
      of the disorder, with more than 65 mutations identified to date. There is not a
      specific treatment for McArdle's disease, but some nutritional treatments in
      combination with aerobic conditioning could improve the quality of life in most
      patients.

PMID- 17217861
TI  - [Echocardiography should be done by cardiologists--anyway until further notice!].

PMID- 17217862
TI  - [Available: a "non-cardiologic" echocardiography].

PMID- 17217863
TI  - [Transthoracic ultrasound: a necessary standard within intensive, acute and pre
      hospital medicine].
AB  - The introduction of focus assessed transthoracic echocardiographic (FATE)
      protocols has brought ultrasound into the first line in evaluating the critically
      ill patient. The technical advancements within ultrasound technology with
      miniaturisation and refinements of equipment have made the advantages of imaging
      available in the hemodynamic monitoring, and this modality now surpasses more
      conventional methods in feasibility and specificity. It seems reasonable to
      expect echocardiography to be incorporated as a new standard in the immediate
      assessment of the critically ill patient in the emergency and the intensive care
      unit as well as in the pre-hospital setting.

PMID- 17217864
TI  - [Heparin and cancer].
AB  - The association between cancer and venous thromboembolism is well described.
      Several studies indicate that elements of the haemostatic system participate in
      tumour genesis. During the last decade a number of post-hoc analyses of trials
      not primarily designed to evaluate the effect of low molecular weight heparins
      (LMWH), on cancer survival, have indicated an increased survival. This has
      recently been supported by results from several prospective trials with LMWH. The
      possible anti-cancer effect of LMWH is not known in details. Treatment regimes
      with LMWH have to be performed.

PMID- 17217865
TI  - [RNA interference--towards individualized genetic medicine].
AB  - RNA interference (RNAi) is an evolutionarily conserved cellular mechanism by
      which gene expression is suppressed by double-stranded RNA (dsRNA) in a sequence
      specific manner. Enzymatically processed dsRNA molecules (siRNAs) target and
      facilitate cleavage of mRNA. By harnessing the RNAi machinery using synthetic or
      DNA-encoded RNA effectors, the siRNA technology offers new therapeutic strategies
      for genetic diseases. We outline the basic mechanisms of RNAi and present state
      of-the-art examples of in vivo siRNA delivery towards development of RNAi-based
      individualized drugs.

PMID- 17217866
TI  - [Glucosamine effectiveness in the treatment of knee osteoarthritis. Presentation
      of a Cochrane analysis with the perspective on the GAIT trial].

PMID- 17217867
TI  - [Focused clinical rotations in the postgraduate specialist training in Denmark].
AB  - Focused clinical rotations are a new concept introduced in the education of
      specialists in Denmark. A focused rotation is a short exposure to a subspecialty
      or a contiguous specialty with the aim of acquiring specific areas of competence.
      The aim of this study is to report on the extent of focused rotation across
      specialties and discuss the rationale and possible impact based on a literature
      search.

PMID- 17217868
TI  - [Skills in management, co-operation and communication in the Pre-Registration
      House Officership].
AB  - INTRODUCTION: In aviation, it has been realised that technical training ensures
      competence in specific procedures, but does not counter errors due to
      communication or decision making in a dynamic environment. As a consequence, Crew
      Resource Management, consisting of training in co-operation, management, and
      communication skills, was introduced in order to serve as a countermeasure
      towards human errors. In the same way, medical school ensures academic and
      technical insight, but rarely offers systematic training in such non-technical
      skills. The aim of this study is to identify the standard of competence in skills
      of co-operation, management, and communication at the end of the Pre-Registration
      House Officership. METHOD: 30 skills of management, co-operation, and
      communication divided into five main areas were identified. Using the Delphi
      method through two rounds of questionnaires, an expert panel of 50 doctors
      evaluated six different standards of competence for each skill. RESULTS: The
      Panel reached consensus at a 75% level for five skills, all within the main area
      "Team communication in the acute situation". Consensus was not reached within any
      of the other four main areas. None of the 30 skills was evaluated as being
      irrelevant for the Pre-Registration House Officer by more than one panel member.
      CONCLUSION: There was broad agreement on the need for high standards of
      competence within the area of team communication. There was considerable
      disagreement within the panel with regard to the other main areas, but all of the
      skills listed in this study were found relevant to the Pre-Registration House
      Officer in the acute situation.

PMID- 17217869
TI  - [Cluster headache (Horton's headache)].
AB  - A cluster headache is an attack of half-sided very strong pain in or behind an
      eye, lasting for up to a few hours with tearing and rhinorrhea and sometimes
      Horner's syndrome. The attacks occur in clusters of weeks' to some months'
      duration. A cluster headache is a neurovascular primary headache which seems to
      involve the hypothalamus. The clinical picture, diagnosis and investigations are
      reviewed. The attack can be treated with oxygen or subcutaneous sumatriptan, and
      verapamil, ergotamine and prednisolone can be successfully used for prophylaxis.
      Early diagnosis and specific treatment are emphazised.

PMID- 17217870
TI  - [Developing COPD--25 years follow-up study of the general population].
AB  - Smokers are more prone to developing chronic obstructive pulmonary disease (COPD)
      than non-smokers. This knowledge comes from studies spanning 10 years or less. We
      used data from The Copenhagen City Heart Study to determine the 25-year absolute
      risk of developing COPD in healthy individuals. The 25-year incidence of moderate
      and severe COPD was 20.7% and 3.6%, respectively. Smoking cessation, especially
      early in the course of the follow-up, decreased the risk substantially. The
      absolute risk of developing COPD among smokers is at least 25%, which is higher
      than previously anticipated.

PMID- 17217871
TI  - [Bartter syndrome--a rare cause of severe polyhydramnios].
AB  - We report a case of a 25-year-old woman, gravida II, Para I, in pregnancy week 26
      + 4 with severe polyhydramnios. The amniotic fluid index was about 39. Type 2
      scanning showed a large urinary bladder only. Treated in pregnancy with repeated
      aminodrinage, total 21 litres. In week 33 + 5, a Caesarean section was performed.
      A girl with Apgar score 10/1, 0/10 was born, weight 1,804 grammes. Immediately
      after birth the child developed polyuria with diuresis, about 8-10 ml/kg/hour,
      electrolyte disturbance, and vomiting, treated with Losec, Gaviscon, indometacin,
      and Vioxx. The diagnosis was Bartter syndrome.

PMID- 17217872
TI  - [Fall or syncope?].
AB  - Falls among older adults are a major health problem. When older adults fall, it
      is difficult to determine whether it is just a simple fall or is caused by
      syncope, as people often have amnesia for the loss of consciousness. We report
      three cases in which cardiac monitoring, for seven days or more, showed that
      falls had been caused by cardiac-related syncopes.

PMID- 17217873
TI  - [Cutaneous lupus erythematosus induced by terbinafine].
AB  - Cutaneous lupus erythematosus can be induced or precipitated by a variety of
      drugs. Among the cutaneous variants of lupus, subacute cutaneous lupus
      erythematosus is the one most often associated with drug intake. The time lag
      between drug intake and skin eruption makes the clinical association less
      obvious, and the condition is often overlooked. We report on a 50-year-old woman
      with previously diagnosed systemic lupus erythematosus who had a severe cutaneous
      flare-up seven weeks after starting treatment with terbinafine for suspected
      onychomycosis.

PMID- 17217874
TI  - [Picture of the month: Twiddler's syndrome].

PMID- 17217876
TI  - [The muscles work, but the brain gets tired].
AB  - Central fatigue is the term used to describe when muscle contractions become
      limited by the ability of the central nervous system to recruit motor neurones.
      Central fatigue becomes manifest when the effort is intense and is associated not
      only with reduced strength but also with an inability to maintain the
      contraction. The contractions thereby resemble those developed during partial
      neuromuscular blockade that mainly affect slow twitch muscle fibres. We suggest
      that central fatigue also manifests as a reduction in the ratio between the
      brain's uptake of oxygen relative to that of carbohydrate from 6 to less than 3.
      This imbalance between oxygen and glucose plus lactate uptake remains unsolved,
      but glycogen and accumulation of intermediates of metabolism are likely to play a
      key role.

PMID- 17217877
TI  - [Sudden cardiac death among young athletes--should we screen?].
AB  - Sudden death involving athletes is always tragic and receives widespread public
      attention. The European Society of Cardiology has proposed cardiovascular
      screening of young competitive athletes. A report from the Danish Society of
      Cardiology recently concluded that screening cannot be recommended in Denmark at
      present. This conclusion was based mainly on inadequate documentation of the
      effect of screening and on considerations regarding cost-effectiveness. We
      recommend other prophylactic measures and further research on this issue.

PMID- 17217878
TI  - [Why Danes are smug--a comparative study of life satisfaction in the EU].
AB  - Danes are by far the most content citizens in the EU. We test a number of
      (im)plausible hypotheses and find that the solid depth of Danish well-being is
      multifactorial, but with two decisive factors: winning the 1992 European
      Championship in football and having constantly low (and undoubtedly realistic)
      expectations for the coming year. With an undoubtedly disappointing 2007 in
      store, we do not wish to foster false hopes. However, some tepid comfort might
      perhaps be taken from the fact that if you lower your expectations enough, you
      might feel a bit better next New Year.

PMID- 17217880
TI  - [Children and physical activity--are the ambitions big enough?].

PMID- 17217881
TI  - [Health diet is a strong medication--but the population don't eat it].

PMID- 17217882
TI  - [Evidence-based medicine: Is healthy diet advice to health people effective?].

PMID- 17217883
TI  - [Oesteogenesis imperfecta--genetics, diagnosis and medical treatment].
AB  - The molecular background for osteogenesis imperfecta (OI) is mutations in one of
      the two genes (COL1A1 and COL1A2) encoding collagen I. The disease is
      characterised by varying degrees of fragile bones, retarded growth, bone
      deformities, tooth abnormalities, blue sclerae, and hearing loss. Treatment with
      bisphosphonates reduces the incidence of fractures in children with severe OI,
      while this still remains to be demonstrated in adults. Results from bone marrow
      transplantation and animal experiments may lead to alternative treatment in
      severe OI.

PMID- 17217884
TI  - [Traction to patients with low-back pain with or without sciatica with the
      reference to The Cochrane Collaboration].

PMID- 17217885
TI  - [Trends in vigorous physical activity versus physical inactivity among 11-15 year
      olds from 1988 to 2002].
AB  - INTRODUCTION: The increasing prevalence of overweight and obesity among children
      and adolescents suggests a need to study the development in main predictors of
      obesity, like eating habits and physical activity. The objective was to describe
      self-reported vigorous physical activity versus physical inactivity among
      children and adolescents over a period of 14 years, 1988-2002. MATERIAL AND
      METHODS: The study population was the Health Behaviour in School-aged Children
      (HBSC) study among nationally representative samples of 11, 13 and 15 year old
      students in 1988, 1991, 1994, 1998, and 2002. The data collection used the
      standardised HBSC questionnaire which included items about vigorous physical
      activity (VPA) outside school hours per week. We defined physically inactivity as
      0 hours of VPA per week and high activity as at least 7 hours of VPA per week.
      RESULTS: The prevalence of high activity was higher among boys than girls and
      increased by age. The prevalence of physically inactive students increased from
      1988 to 2002, especially among the 15 year olds. The proportion of students with
      high activity decreased from 1988 to 2002, especially among the 15 year olds.
      CONCLUSION: A large proportion of children and adolescents do not comply with the
      national recommendations that children should be physically active at least 60
      minutes per day. The physical activity level decreased from 1988 to 2002. There
      is a need for extraordinary efforts to increase physical activity among children
      and adolescents.

PMID- 17217886
TI  - [Insertion of peripheral venous catheter and blood collection].

PMID- 17217887
TI  - [Are Danish medical students concerned about their future job? A questionnaire
      study].
AB  - INTRODUCTION: Knowledge about the thoughts of Danish medical students regarding
      their job future is limited. The aim of this study was to investigate whether
      medical students are concerned about their future work, and if so, to describe
      the types of concerns they have, to what degree they are concerned, possible
      reasons for and consequences of their concerns; furthermore, to evaluate if
      gender and semester influate on the concerns. METHOD: A questionnaire was
      developed based on focus group interviews with medical students. The
      questionnaire was sent to 596 medical students from 3rd, 8th, and 13th semester
      at Copenhagen University. RESULTS: The response rate was 69.9%. A substantial
      number of students (47-90%) were very concerned or concerned to a certain degree
      with regard to aspects of working life that related to the patient and working
      conditions. A positive relation was seen between being highly concerned or
      concerned to a certain degree and daily or often worrying. Possible causes of the
      concerns were related to their experience through their clinical stays, the
      curriculum, comments about the job made by medical doctors and others and their
      own personality. Every sixth student had considered leaving university or
      refraining from entering clinical training due to these concerns. CONCLUSION:
      Medical students from 3rd, 8th, and 13th semester are concerned about their
      future work, especially in relation to the patient, regarding, for example, the
      risk of committing an error or being incompetent in relation to practical skills,
      but also work-related concerns are mentioned.

PMID- 17217888
TI  - [Primary ovarian cancer. A comparison of registrations in the Danish Cancer
      Registry and the Pathology Data Bank].
AB  - INTRODUCTION: Ovarian cancer (OC) registrations in the Danish Cancer Registry
      (CR) and the Danish Pathology Data Bank (PDB) 1978-99 were compared in order to
      assess the possibility of identifying OC cases from another data source than the
      CR. MATERIAL AND METHODS: A total of 13,320 OC were identified in the CR/PDB and
      comparisons of the registrations were performed. RESULTS: The frequency of cases
      registered in both registries increased during 1978-99. Agreement in registration
      of histological subtypes in the two registries was found in 82% of the cases.
      Diagnosis among the rest was most often consistent; however, a more specific
      diagnosis was often found in one or the other registry. The frequency of women
      only registered with OC in the CR decreased from 81% to 35%, as the number of
      women with no diagnoses at all in the PDB declined from 1978 to 1997, whereafter
      it stabilised, primarily because all pathology departments now reported data to
      the PDB. In 1997-99, 29% of OC registered in the CR with a histologically
      verified OC diagnosis was still not registered with cancer in the ovaries in the
      PDB. Most of these, however, could be identified in the PDB with diagnoses
      consistent with metastases from OC. In total, 749 OC were not registered in the
      CR, though explanations for their missing registrations could be found in most
      cases. CONCLUSION: Data from the PDB may not be useful in complete identification
      of ovarian cancer cases for research purposes. However, it is a good supplement
      to data from the CR.

PMID- 17217889
TI  - [Psychotherapeutic day treatment of patients with severe personality disorders.
      Results from the first two years].
AB  - INTRODUCTION: A psychotherapeutic day treatment (DT) for patients with severe
      personality disorders (PD) was established in January 2003, consisting of five
      months of intensive psychodynamic based integrated therapy for 14 patients. This
      paper presents results from the first two years. MATERIAL AND METHODS: 53
      patients were included in a five month combined group psychotherapeutic DT,
      including psychoeducation, cognitive, body, music/drawing and individual therapy.
      Semi-structured interviews were used to assess diagnosis (PSE, SCID-II). SCL-90
      R, self-rating scales and GAF rating (s/f) were used before and after therapy.
      The design was naturalistic. RESULTS: 40 patients (34 women) completed the DT.
      Eight dropped out and five received another treatment. Before treatment: Average
      age 27(SD 6,5), mean GAF= 43 corresponding with unemployment, singles and social
      dysfunctions, high degree of self mutilation, suicide attempts, earlier
      hospitalisations and substance abuse. The most frequent diagnosis was borderline
      disorder 63%. There were co-morbidity with anxiety disorder 48% and depression
      22%. Most importantly, we found a significant reduction in symptoms, significant
      increase in the level of function, reduction in self destructive behaviour, a
      pronounced reduction in hospitalisations and a relatively high degree of
      satisfaction with the treatment programme. CONCLUSION: According to literature,
      effective treatment of patients with severe PD has to be long term, integrated,
      theoretical coherent and focused on compliance. Our study indicates that the
      intensive DT is effective and a good introduction to long term psychotherapy.

PMID- 17217890
TI  - [Treatment of reflex dystrophy with continuous peripheral nerve block].
AB  - Physiotherapy is an important part of the treatment of reflex dystrophy or
      Complex Regional Pain Syndrome (CRPS)-type I, but this treatment is very painful.
      We report two cases of reflex dystrophy: a child with recurrent episodes and an
      adult. Both patients were treated with continuous peripheral nerve block in
      addition to physiotherapy. The method allows complete pain relief. At follow up
      (at 2 and 5 months) the results were excellent. By decreasing pain and thereby
      improving the ability to tolerate physical therapy, this method may have an
      advantage compared to other treatment modalities.

PMID- 17217891
TI  - [Chest pain caused by pancreatic pseudocyst located in the mediastinum].
AB  - Mediastinal pancreatic pseudocyst is a rare condition, causing pulmonary, cardiac
      or oesophageal symptoms. We present a case of a mediastinal pancreatic pseudocyst
      in a 31-year-old male patient who was admitted on suspicion of having an acute
      myocardial infarction because of retrosternal pain. Diagnosis was achieved by CT
      scan, and the pseudocyst was treated by percutanous drainage. The patient
      recovered well with no further need of intervention.

PMID- 17217892
TI  - A newborn with a skin lesion on the back.

PMID- 17217893
TI  - Appropriate use of insulin analogs in an increasingly complex type 2 diabetes
      mellitus (T2DM) landscape.

PMID- 17217894
TI  - Cutaneous melanoma: detecting it earlier, weighing management options.

PMID- 17217895
TI  - Short-course therapy for recurrent genital herpes and herpes labialis.

PMID- 17217896
TI  - Bilateral lesions on the legs.

PMID- 17217897
TI  - How well do family physicians manage skin lesions?

PMID- 17217898
TI  - Clinical inquiries. How effective are dietary interventions in lowering lipids
      for adults with dyslipidemia?

PMID- 17217899
TI  - Clinical inquiries. What GI stress ulcer prophylaxis should we provide
      hospitalized patients?

PMID- 17217900
TI  - Clinical inquiries. What is the best management for patients with evidence of
      asymptomatic ischemia on exercise stress testing?

PMID- 17217901
TI  - Clinical inquiries. What is the best approach to the evaluation of resting
      tachycardia in an adult?

PMID- 17217902
TI  - Clinical inquiries. How do we evaluate a marginally low B12 level?

PMID- 17217903
TI  - Clinical inquiries. What other STI testing should we do for a patient with
      chlamydia?

PMID- 17217904
TI  - A day in the safety net.

PMID- 17217905
TI  - Frequency of heavy episodic drinking among nonfatal injury patients attending an
      emergency room.
AB  - This study investigated the relationship between frequency of heavy episodic
      drinking and nonfatal injury in four categories: environment, external cause,
      diagnosis, and activity at the time of injury. Data were collected over 18 months
      at the emergency room facility of a Swedish hospital. Injury patients aged 18-70
      years answered an alcohol screening questionnaire. Heavy episodic drinking was
      measured as drinking six glasses (72 g alcohol) or more per occasion, for both
      males and females. A total of 2211 patients were enrolled in the study (79.5%
      completion rate). Demographic and drinking characteristics for the patients were
      compared to those of the general population, data for which were derived from a
      population-based survey. The proportion of people who reported heavy episodic
      drinking once a month or more was nearly twice as large among the injury patients
      as in the general population. However, age and sex outweighed heavy episodic
      drinking as risk factors for most injury types. There were 11 significant
      associations between frequency of heavy episodic drinking and injury types in the
      four injury categories, yet no linear trends of increased likelihood of injury
      with increased frequency of heavy episodic drinking could be discerned.

PMID- 17217907
TI  - Polymerization of and in mesophases.
AB  - The use of surfactant mesophases such as vesicular and lyotropic mesophases as
      templates for the preparation of nanostructured polymers by polymerization is
      reviewed. Recent developments using polymerizable and polymeric surfactants in
      mesophase formation and polymerization are also represented with examples. The
      formations of various novel materials including nanocapsules, vesicle-polymer
      architecture, mesoporous polymers and functional nano-composites which would be
      unobtainable through conventional techniques are highlighted. The effects of
      reaction thermodynamics and kinetics on templated polymerizations are also
      discussed.

PMID- 17217906
TI  - The role of attention in horizontal curves: a comparison of advance warning,
      delineation, and road marking treatments.
AB  - Horizontal curves have been recognized as a significant safety issue for many
      years, a more important factor than road width or sight distance. The research
      literature suggests that driver errors associated with horizontal curves result
      from three inter-related problems: failures of driver attention, misperceptions
      of speed and curvature, and poor lane positioning. To examine the roles of
      attentional, perceptual, and lane placement factors in driver behaviour at
      curves, two groups of curve treatments were identified for testing with a driving
      simulator. The first group of treatments consisted of four combinations of
      warning signs designed to alert drivers to the presence of curves and produce a
      reduction in curve approach speeds. The second group was comprised of several
      types of road markings designed to affect drivers' speed and lane position as
      they drove through curves. The results indicated that advance warning signs by
      themselves were not as effective at reducing speeds as when they were used in
      conjunction with chevron sight boards and/or repeater arrows. Of the road marking
      treatments only rumble strips produced any appreciable reductions in speed. A
      herringbones road marking was found to produce significant improvements in
      drivers' lane positions, effectively flattening the drivers' paths through the
      curves. A treatment combining the herringbones treatment with chevron and
      repeater arrow signs produced both a reliable reduction in speed as well as
      improved lane positions. The results are interpreted as evidence that treatments
      that highlight perceptual cues are the most effective means of moderating
      drivers' curve speeds.

PMID- 17217908
TI  - Quantitative study on the microstructure of colloidal fat crystal networks and
      fractal dimensions.
AB  - This paper highlights the most recent progress in the quantitative study on the
      microstructure and the rheological properties of colloidal fat crystal networks.
      Several physical models describing the structural hierarchy of the colloidal fat
      crystal networks are reviewed here, with particular emphasis on fractal model,
      which can be used to explain the scaling behavior of fat crystal networks. The
      concept of the fractal dimension has been extensively used in the quantitative
      study of the microstructure of fat crystal networks and other colloidal networks;
      however, the relationship between the fractal dimension value and microstructural
      characteristics remains somewhat nebulous. Recent computer simulation work from
      our laboratory will be presented relating simulated microstructural features to
      values of particular measure of fractality including the box-counting, particle
      counting and Fourier-transform fractal dimensions.

PMID- 17217909
TI  - Kinetic analyses of divalent cation-dependent EcoRV digestions on a DNA
      immobilized quartz crystal microbalance.
AB  - Enzymatic digestion with a type IIP restriction endonuclease EcoRV was
      investigated on a DNA-immobilized 27-MHz quartz crystal microbalance (QCM). Real
      time observations of both the enzyme binding process and the DNA cleavage process
      of EcoRV were followed by frequency (mass) changes on the QCM, which were
      dependent on divalent cations such as Ca(2+) or Mg(2+). In the presence of
      Ca(2+), the site-specific binding of EcoRV to DNA could be observed, without the
      catalytic process. On the other hand, in the presence of Mg(2+), both the binding
      of the enzyme to the specific DNA (mass increase) and the site-specific cleavage
      reaction (mass decrease) could be observed continuously from QCM frequency
      changes. From time courses of frequency (mass) changes, each kinetic parameter,
      namely binding rate constants (k(on)), dissociation rate constants (k(off)),
      dissociation constants (K(d)) of EcoRV to DNA, and catalytic rate constant
      (k(cat)) of the cleavage reaction, could be determined. The binding kinetic
      parameters of EcoRV in the presence of Ca(2+) were consistent with those of the
      binding process followed by the cleavage process in the presence of Mg(2+). The
      k(cat) value obtained by the QCM method was also consistent with that obtained by
      other methods. This study is the first to simultaneously determine k(on), k(off),
      and k(cat) for a type IIP restriction endonuclease on one device.

PMID- 17217911
TI  - A test of the cognitive content specificity hypothesis in depression and anxiety.
AB  - The present study tested the cognitive content specificity hypothesis (CCSH) to
      assess whether anxiety and depression can be differentiated on the basis of
      cognitive disturbance. One hundred and thirty five depressed participants were
      administered the Beck depression inventory (BDI), the Beck anxiety inventory
      (BAI), the automatic thoughts questionnaire (ATQ) and the anxious self-statements
      questionnaire (ASSQ). It was hypothesised that depressive cognitions would be
      specifically related to, and predictive of, depressive (but not anxiety) symptoms
      in a depressed sample. Conversely, it was predicted that anxiety cognitions would
      be specifically related to, and predictive of, anxiety (but not depressive)
      symptoms in a depressed sample. Results revealed that the ATQ was the sole
      predictor of the BDI and similarly, the ASSQ was the sole predictor of the BAI.
      These findings support the CCSH in depression and provide an integrative
      framework for a greater understanding of the relationship between anxiety and
      depression.

PMID- 17217910
TI  - Modular determinants of antimicrobial activity in platelet factor-4 family
      kinocidins.
AB  - Mammalian platelets contain an array of antimicrobial peptides, termed platelet
      microbicidal proteins (PMPs). Human and rabbit PMPs include known chemokines,
      such as platelet factor-4 (hPF-4); PMP-1 is the rabbit orthologue of hPF-4.
      Chemokines that also exert direct antimicrobial activity have been termed
      kinocidins. A consensus peptide domain library representing mammalian PF-4 family
      members was analyzed to define structural domains contributing to antimicrobial
      activity against a panel of human pathogens. Secondary conformations were
      assessed by circular dichroism spectrometry, and molecular modeling was employed
      to investigate structural correlates of antimicrobial efficacy. Antimicrobial
      activity against isogenic peptide-susceptible or -resistant Staphylococcus
      aureus, Salmonella typhimurium, and Candida albicans strain pairs mapped to the C
      terminal hemimer (38-74) and modular domains thereof (49-63 and 60-74).
      Increasing electrostatic charge and steric bulk were general correlates of
      efficacy. Structural data corroborated spatial distribution of charge, steric
      bulk and putative secondary structure with organism-specific efficacy.
      Microbicidal efficacies of the cPMP antimicrobial hemimer and C-terminal peptide
      (60-74) were retained in a complex human-blood biomatrix assay. Collectively,
      these results suggest that modular determinants arising from structural
      components acting independently and cooperatively govern the antimicrobial
      functions of PF-4 family kinocidins against specific target pathogens.

PMID- 17217912
TI  - Crystal structures of E. coli laccase CueO at different copper concentrations.
AB  - CueO protein is a hypothetical bacterial laccase and a good laccase candidate for
      large scale industrial application. Four CueO crystal structures were determined
      at different copper concentrations. Low copper occupancy in apo-CueO and slow
      copper reconstitution process in CueO with exogenous copper were demonstrated.
      These observations well explain the copper dependence of CueO oxidase activity.
      Structural comparison between CueO and other three fungal laccase proteins
      indicates that Glu106 in CueO constitutes the primary counter-work for
      reconstitution of the trinuclear copper site. Mutation of Glu106 to a Phe
      enhanced CueO oxidation activity and supported this hypothesis. In addition, an
      extra alpha-helix from Leu351 to Gly378 covers substrate biding pocket of CueO
      and might compromises the electron transfer from substrate to type I copper.

PMID- 17217913
TI  - A branched-chain organic acid linked to multiple sclerosis: first identification
      by NMR spectroscopy of CSF.
AB  - (1)H NMR spectroscopy of cerebrospinal fluid (CSF) is currently being used to
      study metabolic profiles characteristic of distinct multiple sclerosis (MS)
      manifestations. For select MS patient groups, we have previously detected
      significantly increased concentrations of several identified metabolites and one
      unidentified compound. We now present, for the first time, the identification of
      the latter molecule, beta-hydroxyisobutyrate (BHIB). A combination of dedicated
      1D and 2D (1)H NMR experiments was employed for signal assignment. To our
      knowledge, BHIB has not previously been identified in (1)H NMR spectra of
      biofluids or biological tissues. Our assignment suggests new biochemical pathways
      involved in specific MS pathologies.

PMID- 17217914
TI  - Induction by NeuroD of the components required for regulated exocytosis.
AB  - NeuroD is a transcriptional factor critical in differentiation of neuronal cells,
      enteroendocrine cells, and pancreatic endocrine cells. However, little is known
      of its roles in cellular functions. We show here that introduction of NeuroD into
      human fetal epithelial cell line Intestine 407 cells induces neuron-like
      morphology. In addition, multiple genes associated with vesicular trafficking and
      exocytotic machinery, including Sec24D, carboxypeptidase E, myosin Va, SNAP25,
      syntaxin 1A, Rab, Rims, Munc18-1, and adenylyl cyclase, were up-regulated by
      NeuroD gene transfer. Moreover, low osmotic pressure-induced exocytosis monitored
      by FM1-43 was enhanced by overexpression of NeuroD. These results suggest that
      NeuroD plays an important role in regulated exocytosis by inducing expressions of
      various components required in the process.

PMID- 17217915
TI  - Quantification of low-expressed mRNA using 5' LNA-containing real-time PCR
      primers.
AB  - Real-time RT-PCR is the most sensitive and accurate method for mRNA
      quantification. Using specific recombinant DNA as a template, real-time PCR
      allows accurate quantification within a 7-log range and increased sensitivity
      below 10 copies. However, when using RT-PCR to quantify mRNA in biological
      samples, a stochastic off-targeted amplification can occur. Classical adjustments
      of assay parameters have minimal effects on such amplification. This undesirable
      amplification appears mostly to be dependent on specific to non-specific target
      ratio rather than on the absolute quantity of the specific target. This drawback,
      which decreases assay reliability, mostly appears when quantifying low-expressed
      transcript in a whole organ. An original primer design using properties of LNA
      allows to block off-target amplification. 5'-LNA substitution strengthens 5'
      hybridization. Consequently on-target hybridization is stabilized and the
      probability for the off-target to lead to amplification is decreased.

PMID- 17217916
TI  - Reactive oxygen species mediates the apoptosis induced by transforming growth
      factor beta(2) in human lens epithelial cells.
AB  - Transforming growth factor beta(2) (TGF-beta(2)), a growth regulator of human
      lens epithelial cells (HLECs), also regulates the death of these cells. Dose
      response analysis showed that the TGF-beta(2) concentration needed to induce
      HLECs death (100 pg/ml) was 10 times that needed to inhibit growth in these cells
      (10 pg/ml). TGF-beta(2)-induced apoptosis in HLECs was preceded by an induction
      of reactive oxygen species (ROS) and a decrease in glutathione in the
      intracellular content, indicating that this factor induces oxidative stress in
      HLECs. Studies performed to analyze the levels of c-fos mRNA, a gene whose
      expression is modulated by the redox state, demonstrated that only high,
      apoptotic concentrations of TGF-beta(2) (100 pg/ml) produced an increase in the
      mRNA levels of this gene, the level of induction being similar to that found when
      cells were incubated in the presence of hydrogen peroxide. Finally, the cell
      death induced by TGF-beta(2) in HLECs was partially blocked by radical
      scavengers, which decreased the percentage of apoptotic cells, whereas these
      agents did not modify the growth-inhibitory effect elicited by TGF-beta(2) in
      these cells. The results presented in this paper provide evidence for the
      involvement of an oxidative process in the apoptosis elicited by TGF-beta(2) in
      HLECs.

PMID- 17217917
TI  - Circumvention of the multidrug-resistance protein (MRP-1) by an antitumor drug
      through specific inhibition of gene transcription in breast tumor cells.
AB  - Multidrug-resistance protein 1 (MRP-1) confers resistance to a number of
      clinically important chemotherapeutic agents. The promoter of the mrp-1 gene
      contains an Sp1-binding site, which we targeted using the antitumor bis
      anthracycline WP631. When MCF-7/VP breast cancer cells, which overexpress MRP-1
      protein, were incubated with WP631 the expression of the multidrug-resistance
      protein gene decreased. Conversely, doxorubicin did not alter mrp-1 gene
      expression. The inhibition of gene expression was followed by a decrease in the
      activity of the MRP-1 protein. The IC(75) for WP631 (drug concentration required
      to inhibit cell growth by 75%) circumvented the drug-efflux pump, without
      addition of resistant modifiers. After treatment with WP631, MCF-7/VP cells were
      committed to die after entering mitosis (mitotic catastrophe), while treatment
      with doxorubicin did not affect cell growth. This is the first report on an
      antitumor drug molecule inhibiting the mrp-1 gene directly, rather than being
      simply a poor substrate for the transporter-mediated efflux. However, both
      situations appeared to coexist, thereby a superior cytotoxic effect was attained.
      Ours results suggest that WP631 offers great potential for the clinical treatment
      of tumors displaying a multidrug-resistance phenotype.

PMID- 17217918
TI  - G1 cell cycle arrest by amlodipine, a dihydropyridine Ca2+ channel blocker, in
      human epidermoid carcinoma A431 cells.
AB  - We demonstrated previously that amlodipine, a dihydropyridine Ca(2+) channel
      blocker, exhibits antitumor effects on human epidermoid carcinoma A431 cells both
      in vitro and in vivo, in part through inhibition of capacitative Ca(2+) entry. In
      this study, we examined the effects of amlodipine on cell cycle distribution and
      cell cycle regulatory molecules in A431 cells, since a rise in intracellular
      Ca(2+) is required at several points during cell cycle progression. Flow
      cytometric analysis revealed that treatment with amlodipine (20-30muM, for 24h)
      induced G1 phase cell accumulation. The amlodipine-induced G1 arrest was
      associated with a decrease in phosphorylation of retinoblastoma protein (pRB), a
      regulator of G1 to S phase transition, reduction of protein levels of cyclin D1
      and cyclin dependent kinase 4 (CDK4), G1 specific cell cycle proteins, and
      increased expression of p21(Waf1/Cip1), an inhibitory protein of CDK/cyclin
      complexes. In vitro kinase assay revealed that amlodipine significantly decreased
      CDK2-, CDK4-, and their partners cyclin E- and cyclin D1-associated kinase
      activities. The amlodipine-induced reductions in cyclin D1 protein expression and
      in CDK2 kinase activity were reproduced by a dihydropyridine derivative,
      nicardipine, having an inhibitory effect on A431 cell growth, but not by
      nifedipine, lacking the antiproliferative activity. Our results demonstrate that
      amlodipine caused G1 cell cycle arrest and growth inhibition in A431 cells
      through induction of p21(Waf1/Cip1) expression, inhibition of CDK/cyclin
      associated kinase activities, and reduced phosphorylation of pRB.

PMID- 17217919
TI  - Interactions of human serum albumin with retinoic acid, retinal and retinyl
      acetate.
AB  - Human serum albumin (HSA), a major plasma protein and plasma-derived therapeutic,
      interacts with a wide variety of drugs and native plasma metabolites. In this
      study the interactions between HSA and small lipophilic molecules all-trans
      retinoic acid (RA), all-trans retinaldehyde (retinal, RAL) and all-trans retinyl
      acetate (RAC) were investigated by UV-vis absorption spectroscopy, fluorescence
      spectroscopy and circular dichroism (CD). This paper focuses on investigation of
      the interactions between HSA and RA by the visible CD. RAL and RAC were used in
      this study due to their structural identity to RA to elucidate the importance of
      the end functional group for the complex formation. Our data demonstrate that RA
      specifically binds to HSA in a stable non-covalent complex at least at two
      internal binding sites with close but distinct affinities. Upon titration of HSA
      with RA, visible CD spectra clearly demonstrate the appearance of a well-defined
      induced positive Cotton Effect (CE) around 350 nm. Beyond ligand-to-protein ratio
      of 0.8 and up to saturation (2.0), CD exhibits two major bands of opposite signs,
      suggesting exciton coupling between the chromophore molecules in the protein
      interior. The fluorescence quenching data suggest proximity of the primary RA
      binding site to tryptophan (W214). RAC shows a weak association with HSA with
      stoichiometry close to that of RA, while interactions of RAL with HSA proceed non
      specifically at multiple sites. Contrary to RA, the adducts of HSA with RAC and
      RAL do not show any induced chirality, thus indicating that despite their high
      structural similarity to RA, both compounds do not appear to occupy the internal
      binding sites, but associate with the protein exterior.

PMID- 17217920
TI  - Selective action of the iminosugar isofagomine, a pharmacological chaperone for
      mutant forms of acid-beta-glucosidase.
AB  - Gaucher disease is a lysosomal glycolipid storage disorder characterized by
      defects in acid-beta-glucosidase (GlcCerase), the enzyme responsible for the
      catabolism of glucosylceramide. We recently demonstrated that isofagomine (IFG),
      an iminosugar that binds to the active site of GlcCerase, enhances the folding,
      transport and activity of the N370S mutant form of GlcCerase. In this study we
      compared the effects of IFG on a number of other glucosidases and
      glucosyltransferases. We report that IFG has little or no inhibitory activity
      towards intestinal disaccharidase enzymes, ER alpha-glucosidase II or
      glucosylceramide synthase at concentrations previously shown to enhance N370S
      GlcCerase folding and trafficking in Gaucher fibroblasts. Furthermore, treatment
      of wild type fibroblasts with high doses of IFG did not alter the processing of
      newly synthesized N-linked oligosaccharides. These findings support further
      evaluation of IFG as a potential therapeutic agent in the treatment of some forms
      of Gaucher disease.

PMID- 17217921
TI  - Brain imaging correlates of depressive symptom severity and predictors of symptom
      improvement after antidepressant treatment.
AB  - BACKGROUND: It would be therapeutically useful to predict clinical response to
      antidepressant drugs. We evaluated structural magnetic resonance imaging (MRI)
      and functional MRI (fMRI) data as predictors of symptom change in people with
      depression. METHODS: Brain structure and function were measured with MRI in 17
      patients with major depression immediately before 8 weeks treatment with
      fluoxetine 20 mg/day. For fMRI, patients were scanned during visual presentation
      of faces representing different intensities of sadness. Clinical response was
      measured by change in serial scores on the Hamilton Rating Scale for Depression.
      Symptom change scores (and baseline symptom severity) were regressed on
      structural and functional MRI data to map brain regions where grey matter volume,
      or activation by sad facial affect processing, was significantly associated with
      symptom change (or baseline severity). RESULTS: Faster rates of symptom
      improvement were strongly associated with greater grey matter volume in anterior
      cingulate cortex, insula, and right temporo-parietal cortex. Patients with
      greater than median grey matter volume in this system had faster rates of
      improvement and significantly lower residual symptom scores after 8 weeks'
      treatment. Faster improvement was also predicted by greater functional activation
      of anterior cingulate cortex. Baseline symptom severity was negatively correlated
      with greater grey matter volume in dorsal prefrontal and anterior midcingulate
      regions anatomically distinct from the pregenual and subgenual cingulate regions
      predicting treatment response. CONCLUSIONS: Structural MRI measurements of
      anterior cingulate cortex could provide a useful predictor of antidepressant
      treatment response.

PMID- 17217922
TI  - Effect of tryptophan hydroxylase-2 gene variants on suicide risk in major
      depression.
AB  - BACKGROUND: Suicide and depressive disorders are strongly associated, yet not all
      depressed patients commit suicide. Genetic factors may partly explain this
      difference. We investigated whether variation at the tryptophan hydroxylase-2
      (TPH2) gene and its 5' upstream region may predispose to suicide in major
      depressive disorder (MDD) and whether this predisposition is mediated by
      impulsive-aggressive behaviors (IABs). METHODS: We genotyped 14 single nucleotide
      polymorphisms (SNPs) in 259 depressed subjects, 114 of which committed suicide
      while depressed. Phenotypic assessments were carried out by means of proxy-based
      interviews. Single-marker and haplotype association analyses were conducted.
      Differences in behavioral and personality traits according to genotypic variation
      were investigated, as well as genetic and clinical predictors of suicide.
      RESULTS: We found two upstream and two intronic SNPs associated with suicide. No
      direct effect of these variants was observed on IABs. However, a slight
      association with reward dependence scores was found. Controlling for suicide risk
      factors, two SNPs (rs4448731 and rs4641527) significantly predicted suicide,
      along with cluster B personality disorders and family history of suicide.
      CONCLUSIONS: The TPH2 gene and its 5' upstream region variants may be involved in
      the predisposition to suicide in MDD; however, our findings do not support the
      role of IABs as mediators.

PMID- 17217923
TI  - DSM-IV personality disorders in the National Comorbidity Survey Replication.
AB  - BACKGROUND: The population prevalence of DSM-IV personality disorders (PDs)
      remains largely unknown. Data are reported here on the prevalence and correlates
      of clinician-diagnosed Clusters A, B, and C DSM-IV PDs in the general population
      of the United States. METHODS: Personality disorder screening questions from the
      International Personality Disorder Examination (IPDE) were administered in Part
      II (n = 5692) of the National Comorbidity Survey Replication (NCS-R). A
      probability sub-sample was then interviewed with the IPDE and used to link
      screening question responses with IPDE clinical diagnoses. The method of Multiple
      Imputation (MI) was then implemented to estimate prevalence and correlates of PDs
      in the full sample. RESULTS: The MI prevalence estimates were 5.7% Cluster A,
      1.5% Cluster B, 6.0% Cluster C, and 9.1% any PD. All three PD clusters were
      significantly comorbid with a wide range of DSM-IV Axis I disorders. Significant
      associations of PDs with functional impairment were largely accounted for by Axis
      I comorbidity. CONCLUSIONS: Strong Axis I comorbidity raises questions about the
      somewhat arbitrary separation of PDs from Axis I disorders in the DSM
      nomenclature. The impairment findings suggest that the main public health
      significance of PDs lies in their effects on Axis I disorders rather than in
      their effects on functioning.

PMID- 17217924
TI  - Tumor necrosis factor-alpha and its inducer inhibit morphine-induced rewarding
      effects and sensitization.
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is emerging as an important
      modulator of the function of the central nervous system (CNS). We have
      demonstrated that TNF-alpha or Leu-Ile, a TNF-alpha inducer, inhibits
      methamphetamine-induced rewarding effects and sensitization. In this study, we
      investigated the effects of TNF-alpha or Leu-Ile on morphine (MOR)-induced
      rewarding effects and sensitization. METHODS: Levels of TNF-alpha messenger RNA
      (mRNA) and protein were determined by real-time reverse transcription polymerase
      chain reaction (RT-PCR) and immunohistochemistry. Effects of TNF-alpha or Leu-Ile
      on MOR-induced rewarding effects and sensitization were investigated by
      conditioned place preference and locomotor activity tests. Extracellular dopamine
      levels were examined using in vivo microdialysis. Effects of TNF-alpha or Leu-Ile
      on MOR-induced antinociceptive effect and withdrawal symptoms were examined by
      hot plate test and naloxone-precipitated withdrawal. RESULTS: Morphine induced
      TNF-alpha mRNA expression via dopamine and opioid receptors. Posttreatment with
      TNF-alpha or Leu-Ile attenuated the MOR-induced place preference and
      sensitization even after their development, as well as pretreatment with TNF
      alpha or Leu-Ile blocked them. An inhibitory effect of Leu-Ile on MOR-induced
      place preference was not observed in TNF-alpha knockout mice. Tumor necrosis
      factor-alpha or Leu-Ile inhibited the increase in extracellular dopamine levels
      in the nucleus accumbens induced by repeated MOR treatment. CONCLUSIONS: These
      results suggest that TNF-alpha inhibits MOR-induced rewarding effect and
      sensitization by regulating extracellular dopamine levels, and Leu-Ile inhibits
      them via the induction of TNF-alpha.

PMID- 17217925
TI  - Catechol-O-methyl transferase and expression of schizophrenia in 73 adults with
      22q11 deletion syndrome.
AB  - BACKGROUND: Catechol-O-methyl transferase (COMT) is a candidate gene for
      schizophrenia with a role in dopamine metabolism, particularly in frontal cortex.
      COMT is within the region commonly deleted in 22q11 deletion syndrome (22q11DS),
      a syndrome with high prevalence of schizophrenia. We examined the role of COMT in
      schizophrenia-related expression in 22q11DS. METHODS: We genotyped the COMT
      functional Val(158/108)Met allele in 73 Caucasian adults with 22q11DS (36 men, 37
      women; aged 33.8, SD 10.1 years; 37 Met, 36 Val hemizygosity) blind to clinical
      data and assessed effects on symptoms and frontal functioning. RESULTS: The lower
      activity Met allele was not significantly more prevalent than the Val allele in
      33 subjects with schizophrenia. Excitement symptoms were more severe, however,
      and three frontal cognitive tests (theory of mind, Trails B, and olfactory
      identification), communication, and social functioning measures showed
      significantly worse performance with Met allele hemizygosity, even after
      accounting for effects of schizophrenia. CONCLUSIONS: The results suggest that
      hemizygosity of the COMT functional allele exerts an effect on some measures of
      frontal functioning in 22q11DS. Elevated levels of tonic dopamine activation
      associated with the COMT Met allele may underlie these aspects of expression. We
      must look elsewhere for causes of the high prevalence of schizophrenia in
      22q11DS, however.

PMID- 17217926
TI  - Diurnal variation in regional brain glucose metabolism in depression.
AB  - BACKGROUND: This study compared diurnal variation in mood and regional cerebral
      metabolic rate of glucose (rCMRglc) in depressed and healthy subjects. METHODS:
      Depressed and healthy subjects were investigated using [18F]-fluoro-deoxyglucose
      positron emission tomography scans during morning and evening wakefulness. All
      subjects completed subjective mood ratings at both times of day. Statistical
      parametric mapping was used to compare rCMRglc between the two groups across time
      of day. RESULTS: Depressed patients showed evening mood improvements compared
      with healthy subjects. Compared with healthy subjects, depressed patients showed
      smaller increases in rCMRglc during evening relative to morning wakefulness in
      lingual and fusiform cortices, midbrain reticular formation, and locus coeruleus
      and greater increases in rCMRglc in parietal and temporal cortices. Depressed
      patients had hypermetabolism in limbic-paralimbic regions and hypometabolism in
      frontal and parietal cortex at both times of day compared with healthy subjects.
      CONCLUSIONS: Variation in rCMRglc differs across times of day in depressed and
      healthy subjects. In depressed patients, evening mood improvements were
      associated with increased metabolic activity in ventral limbic-paralimbic,
      parietal, temporal, and frontal regions and in the cerebellum. This increased
      metabolic pattern during evening wakefulness may reflect partial normalization of
      primary and compensatory neural systems involved in affect production and
      regulation.

PMID- 17217927
TI  - Recall of fear extinction in humans activates the ventromedial prefrontal cortex
      and hippocampus in concert.
AB  - BACKGROUND: Extinction of conditioned fear is thought to form a new safety memory
      that is expressed in the context in which the extinction learning took place.
      Rodent studies implicate the ventromedial prefrontal cortex (vmPFC) and
      hippocampus in extinction recall and its modulation by context, respectively. The
      aim of the present study is to investigate the mediating anatomy of extinction
      recall in healthy humans. METHODS: We used event-related functional magnetic
      resonance imaging (fMRI) and a 2-day fear conditioning and extinction protocol
      with skin conductance response as the index of conditioned responses. RESULTS:
      During extinction recall, we found significant activations in vmPFC and
      hippocampus in response to the extinguished versus an unextinguished stimulus.
      Activation in these brain regions was positively correlated with the magnitude of
      extinction memory. Functional connectivity analysis revealed significant positive
      correlation between vmPFC and hippocampal activation during extinction recall.
      CONCLUSIONS: These results support the involvement of the human hippocampus as
      well as vmPFC in the recall of extinction memory. Furthermore, this provides a
      paradigm for future investigations of fronto-temporal function during extinction
      recall in psychiatric disorders such as posttraumatic stress disorder.

PMID- 17217928
TI  - Impaired endoplasmic reticulum stress response in B-lymphoblasts from patients
      with bipolar-I disorder.
AB  - BACKGROUND: Aberrant intracellular calcium (Ca2+) signaling in patients with
      bipolar-I disorder (BD-I) suggests disturbed endoplasmic reticulum (ER) function
      in BD. We examined whether the ER stress response is altered in BD-I patients and
      the relationship to basal intracellular Ca2+ levels ([Ca2+]B), in B lymphoblasts
      (BLCLs) from BD-I patients. METHODS: Endoplasmic reticulum stress-induced X-box
      binding protein 1 (XBP1), C/EBP homologous protein (CHOP), and GRP78 expression
      in BLCLs from BD-I subjects stratified on elevated or normal [Ca2+]B and control
      subjects were determined by real-time quantitative reverse transcription
      polymerase chain reaction. The XBP1 -116C/G polymorphism, which impairs the XBP1
      loop in the ER stress response, were genotyped with a TaqMan-based assay.
      RESULTS: Compared with control subjects, thapsigargin- and tunicamycin-induced
      increases in XBP1 and CHOP but not GRP78 messenger RNA levels were significantly
      lower in BD-I patients. However, induction of these genes did not differ
      significantly in the two BD-I subgroups stratified on [Ca2+]B. Furthermore, the
      attenuated XBP1 induction cannot be explained solely by differences of XBP1 
      116C/G genotype frequency. CONCLUSIONS: Our findings suggest that the ER stress
      response is impaired in BD-I patients but irrespective of altered intracellular
      Ca2+ homeostasis as reflected in elevated [Ca2+]B. Moreover, an effect of XBP1 
      116C/G polymorphism could not account for the attenuated XBP1 induction in
      bipolar-I disorder observed in this study.

PMID- 17217929
TI  - Three-dimensional laser surface imaging and geometric morphometrics resolve
      frontonasal dysmorphology in schizophrenia.
AB  - BACKGROUND: Although a role for early developmental disturbance(s) in
      schizophrenia is postulated, it has proved difficult to identify hard, biological
      evidence. The brain and face emerge in embryologic intimacy, such that in
      neurodevelopmental disorders, brain dysmorphogenesis is accompanied by facial
      dysmorphogenesis. METHODS: Three-dimensional (3D) laser surface imaging was used
      to capture the facial surface of patients and control subjects in 37 male and 32
      female patients who satisfied DSM-IV criteria for schizophrenia in comparison
      with 58 male and 34 female control subjects. Surface images were analyzed using
      geometric morphometrics and 3D visualizations to identify domains of facial shape
      that distinguish patients from control subjects. RESULTS: Both male and,
      particularly, female patients evidenced significant facial dysmorphology. There
      was narrowing and reduction of the mid to lower face and frontonasal prominences,
      including reduced width and posterior displacement of the mouth, lips, and chin;
      increased width of the upper face, mandible, and skull base, with lateral
      displacement of the cheeks, eyes, and orbits; and anterior displacement of the
      superior margins of the orbits. CONCLUSIONS: The frontonasal prominence, which
      enjoys the most intimate embryologic relationship with the anterior brain and
      also orchestrates aspects of development in maxillary and mandibular domains,
      evidences a characteristic topography of dysmorphogenesis in schizophrenia.

PMID- 17217930
TI  - Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta
      analysis of case-control studies confirm association to substance-related
      disorders, eating disorders, and schizophrenia.
AB  - BACKGROUND: There is an increasing recognition that the pathophysiology of mental
      disorders could be the result of deregulation of synaptic plasticity with
      alterations of neurotrophins. The valine (Val)66-to-methionine (Met) variant,
      located in the pro brain-derived neurotrophic factor (BDNF) sequence, has been
      extensively studied through linkage and association approaches in several
      psychiatric disorders. METHODS: We performed a meta-analysis restricted to
      individual case-control studies in different categories of mental disorders and
      BDNF Val66Met polymorphism. We included data from 39 case-control studies
      encompassing psychiatric phenotypes: eating disorders, substance-related
      disorders, mood disorders, and schizophrenia, among others. RESULTS: The
      association of Val66Met was confined to three diagnoses: substance-related
      disorders, eating disorders, and schizophrenia. The Val/Met and the Met/Met
      genotypes increase the risk for eating disorders up to 33%, while these same
      genotypes confer a 21% protective effect in substance-related disorders. The
      homozygous carriers Met/Met showed a 19% increased risk of schizophrenia with
      respect to the heterozygous state. CONCLUSIONS: The study confirms the
      association of Val66Met to substance-related disorders, eating disorders, and
      schizophrenia. It remains to be determined if other variants in tight linkage
      disequilibrium with Val66Met could configure an extended functional haplotype
      that would explain observed discrepancies in risk estimations across studies.

PMID- 17217931
TI  - Diplotypes of the human serotonin 1B receptor promoter predict growth hormone
      responses to sumatriptan in abstinent alcohol-dependent men.
AB  - BACKGROUND: Some studies have associated alcohol dependence (AD) with the human
      serotonin (5-HT)(1B) receptor (HTR1B). This investigation explored the functional
      responsivity of HTR1B in abstinent AD men using a sumatriptan challenge, while
      measuring genetic heterogeneity in the HTR1B promoter. METHODS: Abstinent AD men
      (n = 27) and abstinent men without any alcohol use disorder (n = 19) were
      administered 6 mg of sumatriptan succinate, subcutaneously. Plasma samples
      collected over the following 2 hours were assayed for growth hormone (GH)
      concentrations. His DNA was genotyped for the A-161T and T-261G polymorphisms of
      the HTR1B promoter and diplotypes determined. RESULTS: Integrated GH responses
      were predicted by interactions of AD and promoter diplotypes, as well as subject
      ethnicity. The final model accounted for nearly 35% of the variance in GH
      responses. Post hoc evaluation revealed that AD was associated with a blunting of
      GH secretion only among individuals with the most common HTR1B diplotype (TT/TT).
      CONCLUSIONS: A blunting of GH responses in abstinent AD men was observed only
      among those with the most common HTR1B promoter diplotype. Less common promoter
      diplotypes appeared protective. Controlling for genetic background is a useful
      augmentation of case-control pharmacological challenge strategies designed to
      elucidate the psychobiology of AD and other complex disorders.

PMID- 17217933
TI  - Evidence for Notch signaling involvement in retinal regeneration of adult newt.
AB  - Involvement of Notch signaling in retinal regeneration by transdifferentiation of
      pigment epithelium cells was investigated using the adult newt Cynops
      pyrrhogaster. During retinal regeneration, cells expressing Notch-1 first
      appeared in the regenerating retina one to two cells thick (stage E-3) originated
      from the retinal pigment epithelium (RPE) cells, and increased in number as the
      regenerating retina increased in thickness. Notch-1 expression was decreased in
      the central retina in association with cell differentiation and became restricted
      to the peripheral retina. Administration of a Notch signaling blocker DAPT
      resulted in the appearance of a cluster of neurons, earlier than in normal
      regeneration, along the regenerating retina 1-3 cells thick (stage E-3 to I-1).
      Immunoblot analysis suggested that DAPT could perturb the processing of Notch-1.
      Similar results were obtained in the newt embryonic retinal development. These
      results suggest that the Notch-1 signaling system may be reset to regulate
      neurogenesis during retinal regeneration. However, PCR analysis revealed that the
      adult newt RPE cells express Hes-1, neurogenin1 and sometimes Delta-1 Hes-1,
      neurogenin1 and sometimes Delta-1 all of which are differently regulated in
      association with retinal regeneration, implying that Notch signaling might also
      be involved early in the process of transdifferentiation.

PMID- 17217932
TI  - Neural substrates of resisting craving during cigarette cue exposure.
AB  - BACKGROUND: In cigarette smokers, the most commonly reported areas of brain
      activation during visual cigarette cue exposure are the prefrontal, anterior
      cingulate, and visual cortices. We sought to determine changes in brain activity
      in response to cigarette cues when smokers actively resist craving. METHODS:
      Forty-two tobacco-dependent smokers underwent functional magnetic resonance
      imaging, during which they were presented with videotaped cues. Three cue
      presentation conditions were tested: cigarette cues with subjects allowing
      themselves to crave (cigarette cue crave), cigarette cues with the instruction to
      resist craving (cigarette cue resist), and matched neutral cues. RESULTS:
      Activation was found in the cigarette cue resist (compared with the cigarette cue
      crave) condition in the left dorsal anterior cingulate cortex (ACC), posterior
      cingulate cortex (PCC), and precuneus. Lower magnetic resonance signal for the
      cigarette cue resist condition was found in the cuneus bilaterally, left lateral
      occipital gyrus, and right postcentral gyrus. These relative activations and
      deactivations were more robust when the cigarette cue resist condition was
      compared with the neutral cue condition. CONCLUSIONS: Suppressing craving during
      cigarette cue exposure involves activation of limbic (and related) brain regions
      and deactivation of primary sensory and motor cortices.

PMID- 17217934
TI  - Aleppo tannin: structural analysis and salivary amylase inhibition.
AB  - The effectiveness and specificity of a tannin inhibition on human salivary
      amylase (HSA) catalyzed hydrolysis was studied using 2-chloro-4-nitrophenyl 4-O
      beta-D-galactopyranosyl-alpha-maltoside (GalG(2)-CNP) and amylose substrates.
      Aleppo tannin was isolated from the gall nut of Aleppo oak. This tannin is a
      gallotannin, in which glucose is esterified with gallic acids. This is the first
      kinetic report, which details the inhibitory effects of this compound on HSA. A
      mixed non-competitive type inhibition has been observed on both substrates. The
      extent of inhibition is markedly dependent on the substrate-type. Kinetic
      constants were calculated from Lineweaver-Burk secondary plots for GalG(2)-CNP
      (K(EI) 0.82 microg mL(-1), K(ESI) 3.3 microg mL(-1)). This indicates a 1:1
      binding ratio of inhibitor-enzyme and/or inhibitor-enzyme-substrate complex. When
      amylose was the substrate the binding ratio of inhibitor to enzyme-substrate
      complex was found to be 2:1, with the binding constants of K(EI) 17.4 microg mL(
      1), K(ESI) 14.9 microg mL(-1), K(ESI(2)) 9.6 microg mL(-1). Presumably, the
      tannin inhibitor can bind not only to HSA, but to the amylose substrate, as well.
      Kinetic data suggest that Aleppo tannin is a more efficient amylase inhibitor
      than the recently studied other tannin with quinic acid core (GalG(2)-CNP: K(EI)
      9.0 microg mL(-1), K(ESI) 47.9 microg mL(-1)).

PMID- 17217935
TI  - Zeolite-catalyzed Helferich-type glycosylation of long-chain alcohols. Synthesis
      of acetylated alkyl 1,2-trans glycopyranosides and alkyl 1,2-cis C2-hydroxy
      glycopyranosides.
AB  - Zeolite-catalyzed glycosylation of long-chain alcohols, using the inexpensive and
      readily available peracetylated beta-D-gluco- and galactopyranoses as glycosyl
      donors under solvent free conditions, has been explored for the first time. Among
      the various forms (H-, Na-, Fe- and Zn) of beta zeolite examined as catalysts in
      the reaction of 1,2,3,4,6-penta-O-acetyl-beta-D-galactopyranose with cetyl
      alcohol, Fe-beta zeolite gave the maximum yield of 63% of cetyl 2,3,4,6-tetra-O
      acetyl-beta-D-galactopyranoside and cetyl 3,4,6-tri-O-acetyl-alpha-D
      galactopyranoside. Fe-beta Zeolite-catalyzed glycosylation was found to be
      general affording the title compounds in each case in a moderate yield, but with
      a good stereoselectivity. The yield of synthetically valuable acetylated long
      chain alkyl 1,2-cis C2-hydroxy-glycopyranosides obtained in the present single
      step procedure is considerably higher than that of the previously reported multi
      step method employing the Stork silicon tether approach.

PMID- 17217937
TI  - Autonomic modulation of electrical restitution, alternans and ventricular
      fibrillation initiation in the isolated heart.
AB  - OBJECTIVE: Abnormal autonomic nerve activity is a strong prognostic marker for
      ventricular arrhythmias but the mechanisms underlying the autonomic modulation of
      ventricular fibrillation (VF) initiation are poorly understood. We examined the
      effects of direct sympathetic (SS) and vagus (VS) nerve stimulation on electrical
      restitution, alternans and VF threshold (VFT) in a novel isolated rabbit heart
      preparation with intact dual autonomic innervation. METHODS: Monophasic Action
      Potentials (MAPs) were recorded from a left ventricular epicardial site on
      innervated, isolated rabbit hearts (n=16). Standard restitution, effective
      refractory period (ERP), electrical alternans and VFT were measured at baseline
      and during SS and VS separately. RESULTS: The restitution curve was shifted
      downwards and made steeper with SS whilst VS caused an upward shift and a
      flattening of the curve. The maximum slope of restitution was increased from
      1.30+/-0.10 at baseline to 1.86+/-0.17 (by 45+/-12%, P<0.01) with SS and
      decreased to 0.69+/-0.10 (by 51+/-6%, P<0.001) with VS. ERP was decreased from
      127.3+/-2.5 ms to 111.8+/-1.8 ms with SS (by 12+/-2%, P<0.001) and increased to
      144.0+/-2.2 ms with VS (by 13+/-2%, P<0.001). VFT was decreased from 4.7+/-0.6 mA
      to 1.9+/-0.5 mA with SS (by 64+/-5%, P<0.001) and increased to 8.7+/-1.1 mA with
      VS (by 89+/-14%, P<0.0005). There was a significant inverse relationship between
      the maximum slope of restitution and VFT (r=-0.63, P<0.0001). When compared with
      baseline, SS caused electrical alternans at longer pacing cycle lengths (139.0+/
      8.4 vs. 123.0+/-7.8 ms, P<0.01) with greater degree of alternans (32.5+/-9.9 vs.
      15.4+/-3.2%, P<0.05). It also caused a wider range of cycle lengths where
      alternans occurred (53.0+/-6.2 vs. 41.0+/-7.0 ms, P<0.05) whilst vagus nerve
      stimulation shortened this range (33.0+/-7.3 ms, P<0.001). CONCLUSIONS:
      Sympathetic stimulation increased maximum slope of restitution and electrical
      alternans but decreased ERP and VF threshold whilst vagus nerve stimulation had
      opposite effects. The interaction between action potential duration and beat-to
      beat interval may play an important role in the autonomic modulation of VF
      initiation.

PMID- 17217936
TI  - CaMKII inhibition protects against necrosis and apoptosis in irreversible
      ischemia-reperfusion injury.
AB  - OBJECTIVES: Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) has been
      implicated in the regulation of cardiac excitation-contraction coupling (ECC) as
      well as in apoptotic signaling and adverse remodeling. The goal of the present
      study is to investigate the role of CaMKII in irreversible ischemia and
      reperfusion (I/R) injury. METHODS: Isovolumic Langendorff perfused rat hearts
      were subjected to global no-flow I/R (45 min/120 min), and isolated myocytes were
      subjected to a protocol of simulated I/R (45 min simulated ischemia/60 min
      reoxygenation) either in the absence or presence of CaMKII inhibition [KN-93 (KN)
      or the CaMKII inhibitory peptide (AIP)]. RESULTS: In I/R hearts, an increase in
      CaMKII activity at the beginning of reperfusion was confirmed by the
      significantly increased phosphorylation of the Thr(17) site of phospholamban. In
      the presence of KN, contractile recovery at the end of reperfusion was almost
      double that of I/R hearts. This recovery was associated with a significant
      decrease in the extent of infarction, lactate dehydrogenase release (necrosis),
      TUNEL-positive cells, caspase-3 activity, and an increase in the Bcl-2/Bax ratio
      (apoptosis). In isolated myocytes, both KN and AIP prevented simulated I/R
      induced spontaneous contractile activity and cell mortality. Similar results were
      obtained when inhibiting the reverse mode Na(+)/Ca(2+) exchanger (NCX) with KB
      R7943, sarcoplasmic reticulum (SR) function with ryanodine and thapsigargin, or
      SR Ca(2+) release with tetracaine. In contrast, overexpression of CaMKII
      decreased cell viability from 52+/-3% to 26+/-2%. CONCLUSIONS: Taken together,
      the present findings are the first to establish CaMKII as a fundamental component
      of a cascade of events integrating the NCX, the SR, and mitochondria that promote
      cellular apoptosis and necrosis in irreversible I/R injury.

PMID- 17217938
TI  - Derepression of pathological cardiac genes by members of the CaM kinase
      superfamily.
AB  - In response to pathologic stresses such as hypertension or myocardial infarction,
      the heart undergoes a remodeling process that is characterized by myocyte
      hypertrophy, myocyte death and fibrosis, resulting in impaired cardiac function
      and heart failure. Cardiac remodeling is associated with derepression of genes
      that contribute to disease progression. This review focuses on evidence linking
      members of the Ca(2+)/calmodulin-dependent protein kinase (CaMK) superfamily,
      specifically CaMKII, protein kinase D (PKD) and microtubule associated kinase
      (MARK), to stress-induced derepression of pathological cardiac gene expression
      through their effects on class IIa histone deacetylases (HDACs).

PMID- 17217939
TI  - Mixed chelate copper complex, Casiopeina IIgly, binds and degrades nucleic acids:
      a mechanism of cytotoxicity.
AB  - Metal-containing drugs that interact with DNA have been designed and studied for
      their anticancer activity. In this study, the mixed chelate copper-based
      anticancer drugs, the casiopeinas, were found to bind to DNA and to degrade DNA
      and RNA in the presence of reducing agents (e.g. ascorbic acid). Casiopeinas
      binding to DNA is high affinity, with harsh wash conditions failing to remove the
      interaction. The reaction requires oxygen, probably involved in the generation of
      *OH radicals, which would be responsible for the strand breakage. The reaction
      was diminished by catalase, and was completely abolished by copper chelators
      (e.g. trientine, EDTA); however, superoxide dismutase (SOD) had no significant
      effect on casiopeina-mediated DNA degradation. Casiopeina IIgly (casIIgly) in the
      presence of ascorbate was capable of degrading RNA, plasmid and genomic DNA, and
      chromatin and intranuclear genetic material. Moreover, catalase and/or SOD
      partially protected cells, ascorbic acid enhanced and trientine, a copper
      chelator, abolished the cytotoxicity of casIIgly. The generation of 8-oxodG in
      cells exposed to casIIgly suggests that the generation of ROS is the major cause
      of the cytotoxicity observed and underlies the high toxicity and anticancer
      activity of these compounds.

PMID- 17217940
TI  - Determination of free L-carnitine in human seminal plasma by high performance
      liquid chromatography with pre-column ultraviolet derivatization and its clinical
      application in male infertility.
AB  - BACKGROUND: To develop and validate a simple and reliable high performance liquid
      chromatographic (HPLC) method for the analysis of free L-carnitine in human
      seminal plasma and to investigate its clinical significance as a potentially
      additional means of evaluating the infertile male. METHODS: After proteins in
      seminal plasma are precipitated with a mixture of acetonitrile and methanol (9:1;
      v/v), free L-carnitine in seminal plasma was derivatized to form its UV-absorbing
      ester. HPLC separation of the sample solution was performed on a Lichrospher SiO2
      column and detected by ultraviolet absorbance at 260 nm. A mobile phase composed
      of acetonitrile-citric acid buffer (containing 12 mmol/L triethanolamine, pH 5.0)
      was found to be the most suitable for this separation at a flow rate of 1.2
      mL/min and enabled the baseline separation of the free L-carnitine from
      interferences with isocratic elution. The free L-carnitine levels in seminal
      plasma were studied in both 30 control subjects and 87 patients with infertility.
      Ejaculates were classified into studied subgroups and defined as:
      asthenozoospermia (n=29), oligozoospermia (n=19) and oligoasthenoteratozoospermia
      (n=39). RESULTS: Under the chromatographic conditions described, the free L
      carnitine derivative had a retention time of approximately 13 min. Good
      separation and detectability of free L-carnitine in human seminal plasma sample
      were obtained. The method proved to be linear in the range of L-carnitine from 0
      micromol/L to 1000 micromol/L. The relative standard deviations of within- and
      between-assay for free L-carnitine analysis were 1.23 and 1.36 %, respectively.
      The recoveries were 91.6-96.5% for the human seminal plasma samples. Free L
      carnitine concentrations in the populations were 392.66+/-107.18 micromol/L in
      the fertile group (n=30), 270.00+/-83.92 micromol/L in asthenozoospermia group,
      187.97+/-43.90 micromol/L in oligozoospermia group and 175.65+/-67.07 micromol/L
      in oligoasthenozoospermia group. The large difference (P<0.01) between the
      fertile and infertile populations is evident and the difference between the
      subdivided groups in the infertile group is not significant (P>0.05). CONCLUSION:
      The determination of free L-carnitine level in seminal plasma may prove useful as
      a potentially biochemical marker of fertility and this is a useful guidance for
      the clinic therapy and the mechanismic study on the male reproduction.

PMID- 17217941
TI  - Serum total cholesterol, HDL-C and LDL-C concentrations significantly correlate
      with the radiological extent of disease and the degree of smear positivity in
      patients with pulmonary tuberculosis.
AB  - BACKGROUND: Low serum total cholesterol (TC) concentrations in patients with
      pulmonary tuberculosis (PTB) have been demonstrated. It was shown that a
      cholesterol-rich diet might accelerate the sterilization rate of sputum cultures
      in PTB patients. It is known that smear positivity might be related to the
      radiological extent of disease (RED) in PTB patients. OBJECTIVE: We hypothesized
      that there might be a relationship between initial serum TC concentrations; the
      degree of RED (DRED) and the degree of smear positivity (DSP) in PTB patients.
      METHOD: Eighty-three PTB patients and 39 healthy controls were included in the
      study. Serum TC, TG, HDL-C, VLDL-C and LDL-C concentrations were determined in
      all subjects. PTB patients were classified for their chest X-ray findings as
      minimal/mild, moderate and advanced. Correlations between serum lipid
      concentrations, DRED and DSP (0, 1+, 2+, 3+, 4+) were investigated. PTB patients
      and controls were also compared for serum lipid concentrations. RESULTS:
      Significant differences between PTB patients and controls were detected for serum
      TC, HDL-C and LDL-C concentrations. On stepwise logistic regression analysis,
      DRED was found as one of the significant independent predictors of serum TC
      levels. We also found significant correlations between DRED and serum HDL-C
      concentrations (r=-0.60, p=0.0001) and between DRED and serum LDL-C
      concentrations (r=-0.28, p=0.011). There were also significant correlations
      between DSP and serum lipid concentrations. CONCLUSION: Our study suggests that
      serum TC, HDL-C and LDL-C concentrations are generally lower in patients with PTB
      than those in healthy controls. In addition, changes in these parameters might be
      related to DRED and DSP in PTB patients.

PMID- 17217942
TI  - Do transposed-letter similarity effects occur at a morpheme level? Evidence for
      morpho-orthographic decomposition.
AB  - When does morphological decomposition occur in visual word recognition? An
      increasing body of evidence suggests the presence of early morphological
      processing. The present work investigates this issue via an orthographic
      similarity manipulation. Three masked priming lexical decision experiments were
      conducted to examine the transposed-letter similarity effect (e.g., jugde
      facilitates JUDGE more than the control jupbe) in polymorphemic and monomorphemic
      words. If morphological decomposition occurs at early stages of visual word
      recognition, we would expect an interaction with transposed-letter effects.
      Experiment 1 was carried out in Basque, which is an agglutinative language. The
      nonword primes were created by transposing two letters that either crossed the
      morphological boundaries of suffixes or did not. Results showed a transposed
      letter effect for non-affixed words, whereas there were no signs of a transposed
      letter effect across morpheme boundaries for affixed words. In Experiment 2, this
      issue was revisited in a non-agglutinative language (Spanish), with prefixed and
      suffixed word pairs. Again, results showed a significant transposed-letter effect
      for non-affixed words, whereas there were no signs of a transposed-letter effect
      across morpheme boundaries for affixed words (both prefixed words and suffixed
      words). Experiment 3 replicated the previous findings, and also revealed that,
      for polymorphemic words, transposed-letter priming effects occurred for within
      morpheme transpositions. Taken together, these findings support the view that
      morphological decomposition operates at an early stage of visual word
      recognition.

PMID- 17217943
TI  - The permeability to water and cryoprotectants of immature and mature oocytes in
      the zebrafish (Danio rerio).
AB  - To identify a stage feasible for the cryopreservation of zebrafish oocytes, we
      investigated the permeability to water and cryoprotectants of immature (stage
      III) and mature (stage V) oocytes. The permeability to water (microm/min/atm) of
      immature oocytes at 25 degrees C (0.37) was significantly higher than that of
      mature oocytes (0.10). The permeability (x10(-3)cm/min) of immature oocytes to
      ethylene glycol, propylene glycol, and Me(2)SO (1.49-3.03) at 25 degrees C was
      substantially higher than that of mature oocytes approximately 0. The
      permeability of immature oocytes to glycerol was also high (1.75), although the
      permeability could not be measured in mature oocytes. Immature oocytes would be
      more suitable than mature oocytes for conservation of the zebrafish.

PMID- 17217944
TI  - Vhnf1 acts downstream of Bmp, Fgf, and RA signals to regulate endocrine beta cell
      development in zebrafish.
AB  - Bmp, Fgf, and retinoic acid (RA) signals have been implicated as regulators of
      pancreas development. However, the integration of these signaling pathways in
      vivo is not fully understood. Variant hnf1 (Vhnf1) is a transcription factor
      involved in pancreas, liver, and kidney development and its mutation in zebrafish
      causes underdeveloped pancreas and liver. We investigated the signaling pathways
      that regulate vhnf1 expression during pancreas development. First, we showed that
      Bmp activity is required for vhnf1 expression in the endoderm. In chordin (a Bmp
      antagonist) morpholino (MO)-injected embryos, vhnf1 expression in endoderm and in
      endocrine beta cells is expanded. On the other hand, in alk8 (a type I TGFbeta
      receptor) MO-injected embryos, vhnf1 expression in the endoderm is significantly
      reduced. Second, we showed that Fgf signaling participates in regulation of
      pancreas development through the vhnf1 pathway. Third, we demonstrated that RA
      fails to rescue reduction of insulin expression in vhnf1 mutants, whereas
      overexpression of vhnf1 restores insulin expression that is repressed by
      treatment with a RA receptor inhibitor. And finally, we revealed that both Bmp
      and Fgf signals act genetically upstream of RA in directing pancreas development.
      Taken together, our data establish that vhnf1 acts downstream of the signaling
      pathways of RA, Bmp, and Fgf to regulate pancreas development in zebrafish.

PMID- 17217945
TI  - Assessment of anandamide's pharmacological effects in mice deficient of both
      fatty acid amide hydrolase and cannabinoid CB1 receptors.
AB  - In the present study, we investigated whether anandamide produces its behavioral
      effects through a cannabinoid CB(1) receptor mechanism of action. The behavioral
      effects of anandamide were evaluated in mice that lacked both fatty acid amide
      hydrolase (FAAH) and cannabinoid CB(1) receptors (DKO) as compared to FAAH (-/-),
      cannabinoid CB(1) (-/-), and wild type mice. Anandamide produced analgesia,
      catalepsy, and hypothermia in FAAH (-/-) mice, but failed to elicit any of these
      effects in the other three genotypes. In contrast, anandamide decreased locomotor
      behavior regardless of genotype, suggesting the involvement of multiple
      mechanisms of action, including its products of degradation. These findings
      indicate that the cannabinoid CB(1) receptor is the predominant target mediating
      anandamide's behavioral effects.

PMID- 17217946
TI  - Impaired acute and inflammatory nociception in mice lacking the p50 subunit of NF
      kappaB.
AB  - The transcription factor NF-kappaB is thought to play an essential role in
      inflammatory processes and pain. However, the in vivo function of individual NF
      kappaB subunits in the development and processing of nociceptive responses is not
      clarified. In this study we investigated the role of the p50 subunit of NF-kappaB
      in models of acute and persistent nociception using NF-kappaB p50(-/-) mice. We
      found that these mice showed impaired basal responses to mechanical as well as
      thermal noxious stimulation in the dynamic plantar as well as the hot plate test,
      respectively, in comparison with wild-type mice. In the formalin test we observed
      a decreased nociceptive behavior in the first and the second phase in NF-kappaB
      p50(-/-) mice. In a model of persistent inflammatory hyperalgesia these mice also
      showed a reduced hyperalgesia to a thermal stimulus, which was in accordance with
      a lower cyclooxygenase-2 expression in the spinal cord after peripheral
      inflammatory stimulation. Taken together, our data indicate that the p50 subunit
      of NF-kappaB is of importance in acute and persistent inflammatory pain. The
      participation to persistent pain might rely on activation of NF-kappaB by
      inflammatory stimuli while the contribution to acute pain responses might be
      related to constitutive NF-kappaB activity in neurons of the nociceptive system.

PMID- 17217947
TI  - Transgenic overexpression of connexin50 induces cataracts.
AB  - To examine the effects of increased expression of Cx50 in the mouse lens,
      transgenic mice were generated using a DNA construct containing the human Cx50
      coding region and a C-terminal FLAG epitope driven by the chicken betaB1
      crystallin promoter. Expression of this protein in paired Xenopus oocytes induced
      gap junctional currents of similar magnitude to wild type human Cx50. Three lines
      of transgenic mice expressing the transgenic protein were analyzed. Lenses from
      transgenic mice were smaller than those from non-transgenic littermates, and had
      cataracts that were already visible at postnatal day 1. Expression of the
      transgene resulted in a 3- to 13-fold increase in Cx50 protein levels above those
      of non-transgenic animals. Light microscopy revealed alterations in epithelial
      cell differentiation, fiber cell structure, interactions between fiber cells and
      areas of liquefaction. Scanning electron microscopy showed fiber cells of varying
      widths with bulging areas along single fibers. Anti-Cx50 and anti-FLAG
      immunoreactivities were detected at appositional membranes and in intracellular
      vesicles in transgenic lenses. N-cadherin, Cx46, ZO-1 and aquaporin 0 localized
      mainly at the plasma membrane, although some N-cadherin and aquaporin 0 was
      associated with the intracellular vesicles. The abundance and
      solubility/integrity of alphaA-, alphaB-, beta- and gamma-crystallin were
      unaffected. These results demonstrate that transgenic expression of Cx50 in mice
      leads to cataracts associated with formation of cytoplasmic vesicles containing
      Cx50 and decreased or slowed epithelial differentiation without major alterations
      in the distribution of other integral membrane or membrane-associated proteins or
      the integrity/solubility of crystallins.

PMID- 17217949
TI  - Hydrogen peroxide oxidation by catalase-peroxidase follows a non-scrambling
      mechanism.
AB  - Despite catalyzing the same reaction (2 H2O2-->2 H2O+O2) heme-containing
      monofunctional catalases and bifunctional catalase-peroxidases (KatGs) do not
      share sequence or structural similarities raising the question of whether or not
      the reaction pathways are similar or different. The production of dioxygen from
      hydrogen peroxide by monofunctional catalases has been shown to be a two-step
      process involving the redox intermediate compound I which oxidizes H2O2 directly
      to O2. In order to investigate the origin of O2 released in KatG mediated H2O2
      degradation we performed a gas chromatography-mass spectrometry investigation of
      the evolved O2 from a 50:50 mixture of H2(18)O2/H2(16)O2 solution containing
      KatGs from Mycobacterium tuberculosis and Synechocystis PCC 6803. The GC-MS
      analysis clearly demonstrated the formation of (18)O2 (m/e = 36) and (16)O2 (m/e
      = 32) but not (16)O(18)O (m/e = 34) in the pH range 5.6-8.5 implying that O2 is
      formed by two-electron oxidation without breaking the O-O bond. Also active site
      variants of Synechocystis KatG with very low catalase but normal or even enhanced
      peroxidase activity (D152S, H123E, W122F, Y249F and R439A) are shown to oxidize
      H2O2 by a non-scrambling mechanism. The results are discussed with respect to the
      catalatic mechanism of KatG.

PMID- 17217948
TI  - Inhibition of RhoA/Rho-kinase pathway suppresses the expression of type I
      collagen induced by TGF-beta2 in human retinal pigment epithelial cells.
AB  - Proliferative vitreoretinopathy (PVR) is a major cause of the failure of
      rhegmatogenous retinal detachment surgery. The pathogenesis of PVR includes a
      fibrotic reaction of retinal pigment epithelial (RPE) cells caused by
      transforming growth factor (TGF)-beta. The cellular mechanisms by which TGF-beta
      induces extracellular matrix protein synthesis are not fully understood. In this
      study, we examined whether the RhoA/Rho-kinase pathway was involved in TGF-beta2
      induced collagen expression in a human RPE cell line, ARPE-19. The roles of RhoA
      and Rho-kinase were evaluated using biochemical inhibitors, RhoA inhibitor,
      simvastatin and Rho-kinase inhibitor, Y27632. The effects of simvastatin or
      Y27632 on the type I collagen mRNA (COL1A1 and COL1A2) expression induced by TGF
      beta2 were evaluated by real-time RT-PCR. The effects of simvastatin or Y27632 on
      type I collagen synthesis induced by TGF-beta2 were assessed by
      immunocytochemical analysis with anti-type I collagen antibody. To examine the
      effects of simvastatin or Y27632 on COL1A2 promoter activity induced by TGF
      beta2, luciferase reporter assays were also performed. Moreover, the role of RhoA
      itself on COL1A2 promoter activity was assessed using the constructs of
      constitutively active RhoA and dominant-negative RhoA. RhoA was activated within
      5 min after stimulation with TGF-beta2, and its activation persisted for as long
      as 1 h in a dose-dependent fashion. Preincubation of ARPE-19 with simvastatin (5
      microM) or Y27632 (10 microM) significantly prevented TGF-beta2-induced COL1A1
      and COL1A2 gene expression. Inhibition of RhoA/Rho-kinase markedly suppressed TGF
      beta2-induced type I collagen synthesis in ARPE-19. Moreover, the blockage of
      RhoA/Rho-kinase inhibited the increase in COL1A2 promoter activity when induced
      by TGF-beta2. Constitutively active RhoA increased COL1A2 promoter activity in
      the presence or absence of TGF-beta2. Simvastatin and Y27632 reduced active RhoA
      induced COL1A2 promoter activity. The dominant-negative RhoA inhibited COL1A2
      promoter activity augmentation induced by TGF-beta2. In the luciferase assay
      using a mutation construct of the Smad binding site in COL1A2 promoter (Smad
      mut/Luc), the treatment with simvastatin and Y27632 significantly reduced TGF
      beta2 induction of Smad-mut/Luc promoter activity. On the other hand, both
      simvastatin and Y27632 significantly reduced CAGA12-Luc activity induced by TGF
      beta2. These results indicate that the RhoA/Rho-kinase pathway plays a role in
      relaying TGF-beta2 signal transduction to type I collagen synthesis in RPE cells
      in a Smad-dependent and Smad-independent fashion. The RhoA/Rho-kinase pathway may
      be a therapeutic target for treating PVR.

PMID- 17217950
TI  - Beyond the epithelium: cadherin function in fibrous connective tissues.
AB  - In fibrous connective tissues, fibroblasts are organized into syncytia, cellular
      networks that enable matrix remodeling and that are interconnected by
      intercellular adherens junctions (AJs). The AJs of fibroblasts are mediated by N
      cadherin, a broadly expressed classical cadherin that is critically involved in
      developmental processes, wound healing and several diseases of mesenchymal
      tissues. In contrast to E-cadherin-dependent junctions of epithelia, the
      formation of AJs in fibrous connective tissues is relatively uncharacterized.
      Work over the last several years has documented an expanding list of molecules
      which function to regulate N-cadherin mediated junctions such as: Fer, PTP1B,
      cortactin, calcium, gelsolin, PIP5KIgamma, PIP2, and the Rho family of GTPases.
      We present an overview on the regulation of N-cadherin-mediated junction
      formation that highlights recent molecular advances in the field and rationalizes
      the roles of N-cadherin in connective tissue function.

PMID- 17217951
TI  - Back or neck-pain-related disability of nursing staff in hospitals, nursing homes
      and home care in seven countries--results from the European NEXT-Study.
AB  - BACKGROUND: Musculoskeletal disorders are a widespread affliction in the nursing
      profession. Back or neck-pain-related disability of nursing staff is mainly
      attributed to physical and psychosocial risk factors. OBJECTIVES: To investigate
      which-and to what extent-physical and psychosocial risk factors are associated
      with neck/back-pain-related disability in nursing, and to assess the role of the
      type of health care institution (hospitals, nursing homes and home care
      institutions) within different countries in this problem. DESIGN: Cross-sectional
      secondary analysis of multinational data of nurses and auxiliary staff in
      hospitals (n=16,770), nursing homes (n=2140) and home care institutions (n=2606)
      in seven countries from the European NEXT-Study. METHODS: Multinomial logistic
      regression analysis with raw models for each factor and mutually adjusted with
      all analysed variables. RESULTS: Analysis of the pooled data revealed effort
      reward imbalance as the predominant risk factor for disability in all settings
      (odds ratios for high disability by effort-reward ratio: hospital 5.05 [4.30
      5.93]; nursing home 6.52 [4.04-10.52] and home care 6.4 [3.83-10.70] [after
      mutual adjustment of psychosocial and physical risk factors]). In contrast,
      physical exposure to lifting and bending showed only limited associations with
      odds ratios below 1.6; the availability and use of lifting aids was-after mutual
      adjustment-not or only marginally associated with disability. These findings were
      basically confirmed in separate analyses for all seven countries and types of
      institutions. CONCLUSIONS: The findings show a pronounced association between
      psychosocial factors and back or neck-pain-related disability. Further research
      should consider psychosocial factors and should take the setting where nurses
      work into account.

PMID- 17217952
TI  - Behaviour of sulphonated azodyes in ion-pairing reversed-phase high-performance
      liquid chromatography.
AB  - Ion-pairing reversed-phase high-performance liquid chromatography (RP-HPLC)
      operation conditions were studied to obtain information useful for development
      and optimization of separation methods suitable for HPLC/MS analysis of dyes. The
      retention of eight sulphonated azodyes with widely differing structures (1-5 acid
      groups, molecular weight range 350-1220) was measured in mobile phases containing
      various ion-pairing reagents in aqueous-methanolic mobile phases. The effects of
      the type and of the concentration of ammonium acetate, tetrabutylammonium
      hydrogen sulphate and five di- and tri-alkylammonium acetate ion-pairing reagents
      on the chromatographic behaviour of dyes were compared in mobile phases with
      varying concentrations of methanol. Structural effects on the retention of dyes
      were studied in detail. The retention scale based on lipophilic and polar indices
      can be used for optimization of mobile phase for HPLC/MS of dyes and, on the
      other hand, may provide some information on the structure of unknown dyes.

PMID- 17217953
TI  - Detection of weak ligand interactions of leukocyte Ig-like receptor B1 by
      fluorescence correlation spectroscopy.
AB  - Fluorescence correlation spectroscopy (FCS) can directly and quickly detect the
      translational diffusion of individual fluorescence-labeled molecules in
      solutions. Although FCS analyses for protein-protein interactions have been
      performed, the very weak interactions generally observed in cell-cell recognition
      of the immune system have not been examined in detail. Here, we report the FCS
      analysis for low-affinity and fast-kinetic binding (K(d) greater than muM range)
      of the human inhibitory immune cell surface receptor, leukocyte immunoglobulin
      like receptor B1 (LILRB1), to its ligands, MHC (major histocompatibility complex)
      class I molecules (MHCIs) by using the single-molecule FCS detection system which
      requires only a small amount of sample. Since the random labeling technique for
      LILRB1 disturbed the MHCI binding, we performed site-specific labeling of LILRB1
      by introducing a cysteine residue at the C-terminus, which could be covalently
      attached with the fluorescence reagent, Alexa647. This technique can be applied
      to other type I membrane receptors. The low-affinity binding of LILRB1-Alexa647
      to MHCIs (HLA-Cw4, and -G1) was detected by FCS, even though non-labeled MHCIs
      were only twice as big as the labeled LILRB1. Their dissociation constants (7.5
      muM (HLA-Cw4) and 5.7 muM (HLA-G1)) could be determined and were consistent with
      surface plasmon resonance (SPR) data. These results indicate that the single
      molecule FCS detection system is capable of analyzing the binding characteristics
      of immune cell surface receptors even in difficult cases such as (1) small amount
      of protein samples, (2) small difference in molecular weight and (3) weak
      affinity. Therefore, it is a powerful tool for characterization and high
      throughput inhibitor screening of a wide variety of cell-cell recognition
      receptors involved in immunologically relevant events.

PMID- 17217954
TI  - Experimental infection of Apis mellifera honeybees with Nosema ceranae
      (Microsporidia).
AB  - In this report, an experimental infection of Apis mellifera by Nosema ceranae, a
      newly reported microsporidian in this host is described. Nosema free honeybees
      were inoculated with 125,000 N. ceranae spores, isolated from heavily infected
      bees. The parasite species was identified by amplification and sequencing the
      SSUrRNA gene of the administered spores. Three replicate cages of 20 honeybees
      each were prepared, along with one control cage (n=20) supplied with sugar syrup
      only. The infection rate was 100% at the dosage administered. The presence of
      Nosema inside ventricular cells was confirmed in the samples using ultrathin
      sectioning and transmission electron microscopy. By day 3 p.i. a few cells
      (4.4%+/-1.2) were observed to be parasitized, whereas by 6 days p.i. more than
      half of the counted cells (66.4%+/-6) showed different parasite stages, this
      value increasing on day 7 p.i. (81.5%+/-14.8). Only one control bee died on day 7
      p.i. In the infected groups, mortality was not observed until day 6 p.i. (66.7%+/
      5.6). Total mortality on day 7 p.i. was 94.1% in the three infected replicates
      and by day 8 p.i. no infected bee was alive. After the infection, the parasites
      invaded both the tip of folds and the basal cells of the epithelium and the
      autoinfective capacity of the spores seemed to spread the infection rapidly
      between epithelial cells. On day 3 p.i., mature spores could be seen inside host
      cell tissue implying that the developmental cycle had been completed. The large
      number of parasitized cells, even the regenerative ones, the presence of
      autoinfective spores and the high mortality rate demonstrate that N. ceranae is
      highly pathogenic to Apis mellifera. Possible relation with bee depopulation
      syndrome is discussed by authors.

PMID- 17217955
TI  - Mechanisms by which epoxyeicosatrienoic acids (EETs) elicit cardioprotection in
      rat hearts.
AB  - Cytochrome P450 (CYP) epoxygenases and their arachidonic acid (AA) metabolites,
      the epoxyeicosatrienoic acids (EETs), have been shown to produce reductions in
      infarct size in canine myocardium following ischemia-reperfusion injury via
      opening of either the sarcolemmal K(ATP) (sarcK(ATP)) or mitochondrial K(ATP)
      (mitoK(ATP)) channel. In the present study, we subjected intact rat hearts to 30
      min of left coronary artery occlusion and 2 h of reperfusion followed by
      tetrazolium staining to determine infarct size as a percent of the area at risk
      (IS/AAR, %). The results demonstrate that the two major regioisomers of the CYP
      epoxygenase pathway, 11,12-EET (2.5 mg/kg, iv) and 14,15-EET (2.5 mg/kg, iv)
      significantly reduced myocardial infarct size (IS/AAR, %) in rats as compared
      with control (41.9+/-2.3%, 40.9+/-1.2% versus 61.5+/-1.6%, respectively),
      whereas, a third regioisomer, 8,9-EET (2.5 mg/kg, iv) had no effect (55.2+/-1.4).
      The protective effect of pretreatment with 11,12- and 14,15-EETs was completely
      abolished (61.9+/-0.7%, 58.6+/-3.1%, HMR; 63.3+/-1.2%, 63.2+/-2.5%, 5-HD) in the
      presence of the selective sarcK(ATP) channel antagonist, HMR 1098 (6 mg/kg, iv)
      or the selective mitoK(ATP) channel antagonist, 5-HD (10 mg/kg, iv) given 10 min
      after 11,12- or 14,15-EET administration but 5 min prior to index ischemia.
      Furthermore, concomitant pretreatment with 11,12- or 14,15-EET in combination
      with the free radical scavenger, 2-mercaptopropionyl glycine (2-MPG), at a dose
      (20 mg/kg, iv) that had no effect on IS/AAR (57.7+/-1.3%), completely abolished
      the cardioprotective effect of 11,12- and 14,15-EETs (58.2+/-1.6%, 61.4+/-1.0%),
      respectively. These data suggest that part of the cardioprotective effects of
      EETs in rat hearts against infarction is the result of an initial burst of
      reactive oxygen species (ROS) and subsequent activation of both the sarcK(ATP)
      and mitoK(ATP) channel.

PMID- 17217956
TI  - NADPH oxidase inhibition prevents cocaine-induced up-regulation of xanthine
      oxidoreductase and cardiac dysfunction.
AB  - Oxidative stress is involved in the pathogenesis of cocaine-induced
      cardiomyopathy. In the present study, we aimed to determine the enzymatic sources
      of reactive oxygen species (ROS) production, namely NADPH oxidase and xanthine
      oxidoreductase (XOR) in male Wistar rats treated for 7 days with cocaine (2x7.5
      mg/kg/day, ip) or cocaine with a NADPH oxidase inhibitor (apocynin, 50 mg/kg/day,
      po) or a XOR inhibitor (allopurinol, 50 mg/kg/day, po). Cocaine-induced cardiac
      dysfunction is associated with an increase in NADPH oxidase and XOR activities
      (59% and 29%, respectively) and a decrease in catalase activity. Apocynin or
      allopurinol treatment prevents the cocaine-induced cardiac alteration by
      restoration of cardiac output, stroke volume and fractional shortening. This is
      associated with a reduction of the myocardial production of superoxide anions and
      an enhancement of catalase activity. Surprisingly, apocynin treatment prevents
      XOR up-regulation supporting the hypothesis that NADPH oxidase-derived ROS play a
      role in modulating ROS production by XOR. These data suggest that NADPH and
      xanthine oxidase act synergically to form myocardial ROS and clearly demonstrate
      that their inhibition may be critical in preventing the initiation and
      progression of cocaine-induced LV dysfunction.

PMID- 17217957
TI  - Physical responses of bacterial chemoreceptors.
AB  - Chemoreceptors of the bacterium Escherichia coli are thought to form trimers of
      homodimers that undergo conformational changes upon ligand binding and thereby
      signal a cytoplasmic kinase. We monitored the physical responses of trimers in
      living cells lacking other chemotaxis proteins by fluorescently tagging receptors
      and measuring changes in fluorescence anisotropy. These changes were traced to
      changes in energy transfer between fluorophores on different dimers of a trimer:
      attractants move these fluorophores farther apart, and repellents move them
      closer together. These measurements allowed us to define the responses of bare
      receptor oligomers to ligand binding and compare them to the corresponding
      response in kinase activity. Receptor responses could be fit by a simple "two
      state" model in which receptor dimers are in either active or inactive
      conformations, from which energy bias and dissociation constants could be
      estimated. Comparison with responses in kinase-activity indicated that higher
      order interactions are dominant in receptor clusters.

PMID- 17217958
TI  - Examination of the long-range effects of aminofluorene-induced conformational
      heterogeneity and its relevance to the mechanism of translesional DNA synthesis.
AB  - Adduct-induced conformational heterogeneity complicates the understanding of how
      DNA adducts exert mutation. A case in point is the N-deacetylated AF lesion [N
      (2'-deoxyguanosin-8-yl)-2-aminofluorene], the major adduct derived from the
      strong liver carcinogen N-acetyl-2-aminofluorene. Three conformational families
      have been previously characterized and are dependent on the positioning of the
      aminofluorene rings: B is in the "B-DNA" major groove, S is "stacked" into the
      helix with base-displacement, and W is "wedged" into the minor groove. Here, we
      conducted (19)F NMR, CD, T(m), and modeling experiments at various primer
      positions with respect to a template modified by a fluorine tagged AF-adduct
      (FAF). In the first set, the FAF-G was paired with C and in the second set it was
      paired with A. The FAF-G:C oligonucleotides were found to preferentially adopt
      the B or S-conformers while the FAF-G:A mismatch ones preferred the B and W
      conformers. The conformational preferences of both series were dependent on
      temperature and complementary strand length; the largest differences in
      conformation were displayed at lower temperatures. The CD and T(m) results are in
      general agreement with the NMR data. Molecular modeling indicated that the
      aminofluorene moiety in the minor groove of the W-conformer would impose a steric
      clash with the tight-packing amino acid residues on the DNA binding area of the
      Bacillus fragment (BF), a replicative DNA polymerase. In the case of the B-type
      conformer, the carcinogenic moiety resides in the solvent-exposed major groove
      throughout the replication/translocation process. The present dynamic NMR
      results, combined with previous primer extension kinetic data by Miller &
      Grollman, support a model in which adduct-induced conformational heterogeneities
      at positions remote from the replication fork affect polymerase function through
      a long-range DNA-protein interaction.

PMID- 17217960
TI  - Catabolism of phenylalanine by Pseudomonas putida: the NtrC-family PhhR regulator
      binds to two sites upstream from the phhA gene and stimulates transcription with
      sigma70.
AB  - Pseudomonas putida uses L-phenylalanine as the sole nitrogen source for growth by
      converting L-phenylalanine to L-tyrosine, which acts as a donor of the amino
      group. This metabolic step requires the products of the phhA and phhB genes,
      which form an operon. Expression of the phhA promoter is mediated by the phhR
      gene product in the presence of L-phenylalanine or L-tyrosine. The PhhR protein
      belongs to the NtrC family of enhancers. In contrast with most members of this
      family of regulators, transcription from the promoter of the phhAB operon
      (P(phhA)) is mediated by RNA polymerase with sigma(70) rather than with
      sigma(54). The PhhR regulator binds two similar but non-identical upstream PhhR
      motifs (5'-TGTAAAATTATCGTTACG-3' and 5'-ACAAAAACTGTGTTTCCG-3') that are located
      39 and 97 nucleotides upstream of the proposed -35 hexamer for RNA polymerase,
      respectively. These motifs are called PhhR proximal and PhhR distal binding
      motifs because of their position with respect to the RNA polymerase binding site.
      Affinity of PhhR for its target sequences was determined by isothermal titration
      calorimetry and was found to be around 30 nM for the proximal site and 2 microM
      for the distal site, and the binding stoichiometry is of a dimer per binding
      site. Both target sequences are sine qua non requirements for transcription,
      since inactivation of either of them resulted in no transcription from the phhA
      promoter. An IHF binding site overlaps the proximal PhhR proximal motif, which is
      recognized by IHF with a K(D) of around 1.2 microM. IHF may consequently compete
      with PhhR for binding and indeed inhibits PhhR-dependent phhAB operon expression.

PMID- 17217959
TI  - A structural core within apolipoprotein C-II amyloid fibrils identified using
      hydrogen exchange and proteolysis.
AB  - Plasma apolipoproteins show alpha-helical structure in the lipid-bound state and
      limited conformational stability in the absence of lipid. This structural
      instability of lipid-free apolipoproteins may account for the high propensity of
      apolipoproteins to aggregate and accumulate in disease-related amyloid deposits.
      Here, we explore the properties of amyloid fibrils formed by apolipoproteins
      using human apolipoprotein (apo) C-II as a model system. Hydrogen-deuterium
      exchange and NMR spectroscopy of apoC-II fibrils revealed core regions between
      residues 19-37 and 57-74 with reduced amide proton exchange rates compared to
      monomeric apoC-II. The C-terminal core region was also identified by partial
      proteolysis of apoC-II amyloid fibrils using endoproteinase GluC and proteinase
      K. Complete tryptic hydrolysis of apoC-II fibrils followed by centrifugation
      yielded a single peptide in the pellet fraction identified using mass
      spectrometry as apoC-II(56-76). Synthetic apoC-II(56-76) readily formed fibrils,
      albeit with a different morphology and thioflavinT fluorescence yield compared to
      full-length apoC-II. Studies with smaller peptides narrowed this fibril-forming
      core to a region within residues 60-70. We postulate that the ability of apoC
      II(60-70) to independently form amyloid fibrils drives fibril formation by apoC
      II. These specific amyloid-forming regions within apolipoproteins may underlie
      the propensity of apolipoproteins and their peptide derivatives to accumulate in
      amyloid deposits in vivo.

PMID- 17217961
TI  - Gene duplication of the eight-stranded beta-barrel OmpX produces a functional
      pore: a scenario for the evolution of transmembrane beta-barrels.
AB  - The repeating unit of outer membrane beta-barrels from Gram-negative bacteria is
      the beta-hairpin, and representatives of this protein family always have an even
      strand number between eight and 22. Two dominant structural forms have eight and
      16 strands, respectively, suggesting gene duplication as a possible mechanism for
      their evolution. We duplicated the sequence of OmpX, an eight-stranded beta
      barrel protein of known structure, and obtained a beta-barrel, designated Omp2X,
      which can fold in vitro and in vivo. Using single-channel conductance
      measurements and PEG exclusion assays, we found that Omp2X has a pore size
      similar to that of OmpC, a natural 16-stranded barrel. Fusions of the homologous
      proteins OmpX, OmpA and OmpW were able to fold in vitro in all combinations
      tested, revealing that the general propensity to form a beta-barrel is sufficient
      to evolve larger barrels by simple genetic events.

PMID- 17217962
TI  - Interaction of a G protein-coupled receptor with a G protein-derived peptide
      induces structural changes in both peptide and receptor: a Fourier-transform
      infrared study using isotopically labeled peptides.
AB  - G protein-coupled receptor signaling involves productive interaction between
      agonist-activated receptor and G protein. We have used Fourier-transform infrared
      difference spectroscopy to examine the interaction between the active Meta II
      state of the visual pigment rhodopsin with a peptide analogue corresponding to
      the C terminus of the alpha-subunit of the G protein transducin. Formation of the
      receptor-peptide complex evokes a spectral signature consisting of
      conformationally sensitive amide I and amide II difference bands. In order to
      distinguish between amide backbone contributions of the peptide and of the
      receptor moiety to the vibrational spectra, we employed complete (13)C,(15)N
      labeling of the peptide. This isotopic labeling downshifts selectively the bands
      of the peptide, which can thus be extracted. Our results show that formation of
      the complex between the activated Meta II receptor state and the peptide is
      accompanied by structural changes of the peptide, and of the receptor, indicating
      that the conformation of the Meta II.peptide complex is different from that of
      Meta II. This result implies that the activated receptor state has conformational
      flexibility. Binding of the peptide to the activated receptor state stabilizes a
      substate that deviates from that stabilized only by the agonist.

PMID- 17217963
TI  - Crystal structure of D-erythronate-4-phosphate dehydrogenase complexed with NAD.
AB  - Pyridoxal-5'-phosphate (the active form of vitamin B6) is an essential cofactor
      in many enzymatic reactions. While animals lack any of the pathways for de novo
      synthesis and salvage of vitamin B6, it is synthesized by two distinct
      biosynthetic routes in bacteria, fungi, parasites, and plants. One of them is the
      PdxA/PdxJ pathway found in the gamma subdivision of proteobacteria. It depends on
      the pdxB gene, which encodes erythronate-4-phosphate dehydrogenase (PdxB), a
      member of the d-isomer specific 2-hydroxyacid dehydrogenase superfamily. Although
      three-dimensional structures of other functionally related dehydrogenases are
      available, no structure of PdxB has been reported. To provide the missing
      structural information and to gain insights into the catalytic mechanism, we have
      determined the first crystal structure of erythronate-4-phosphate dehydrogenase
      from Pseudomonas aeruginosa in the ligand-bound state. It is a homodimeric enzyme
      consisting of 380-residue subunits. Each subunit consists of three structural
      domains: the lid domain, the nucleotide-binding domain, and the C-terminal
      dimerization domain. The latter domain has a unique fold and is largely
      responsible for dimerization. Interestingly, two subunits of the dimeric enzyme
      are bound with different combinations of ligands in the crystal and they display
      significantly different conformations. Subunit A is bound with NAD and a
      phosphate ion, while subunit B, with a more open active site cleft, is bound with
      NAD and l(+)-tartrate. Our structural data allow a detailed understanding of
      cofactor and substrate recognition, thus providing substantial insights into PdxB
      catalysis.

PMID- 17217964
TI  - Essential role of proline isomerization in stefin B tetramer formation.
AB  - Here we present the tetrameric structure of stefin B, which is the result of a
      process by which two domain-swapped dimers of stefin B are transformed into
      tetramers. The transformation involves a previously unidentified process of
      extensive intermolecular contacts, termed hand shaking, which occurs concurrently
      with trans to cis isomerization of proline 74. This proline residue is widely
      conserved throughout the cystatin superfamily, a member of which, human cystatin
      C, is the key protein in cerebral amyloid angiopathy. These results are
      consistent with the hypothesis that isomerization of proline residues can play a
      decisive role in amyloidogenesis.

PMID- 17217965
TI  - Conformational transitions of adenylate kinase: switching by cracking.
AB  - Conformational heterogeneity in proteins is known to often be the key to their
      function. We present a coarse grained model to explore the interplay between
      protein structure, folding and function which is applicable to allosteric or non
      allosteric proteins. We employ the model to study the detailed mechanism of the
      reversible conformational transition of Adenylate Kinase (AKE) between the open
      to the closed conformation, a reaction that is crucial to the protein's catalytic
      function. We directly observe high strain energy which appears to be correlated
      with localized unfolding during the functional transition. This work also
      demonstrates that competing native interactions from the open and closed form can
      account for the large conformational transitions in AKE. We further characterize
      the conformational transitions with a new measure Phi(Func), and demonstrate that
      local unfolding may be due, in part, to competing intra-protein interactions.

PMID- 17217966
TI  - Third cranial nerve palsy? Look for a sicca syndrome.
AB  - Sjogren's syndrome (SS) is a systemic autoimmune disorder, and neurological
      involvement may frequently occur. Here we describe a 79-year-old woman who came
      to our attention for a sudden right incomplete 3rd cranial nerve palsy. Following
      extensive investigations, a diagnosis of primary SS was reached, and the patient
      recovered after treatment with ev Ig and steroids. Therefore, we suggest that SS
      should be considered in apparently idiopathic 3rd cranial nerve palsies, since,
      with the appropriate treatment, they might be transient and reversible.

PMID- 17217967
TI  - Antiarrhythmic effect of atorvastatin on autoimmune myocarditis is mediated by
      improving myocardial repolarization.
AB  - 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins,
      are known to inhibit cholesterol biosynthesis and prevent inflammation and
      oxidative stress. To explore the effects of atorvastatin on inflammatory
      progression and major cardiac electrophysiological changes in myocarditis, we
      used an animal model of experimental autoimmune myocarditis (EAM). In this model,
      BALB/c mice were treated with atorvastatin and we evaluated the levels of
      inflammation markers and currents of ionic channels that contribute to the
      duration of action potential (APD) of ventricular myocytes. We demonstrated that
      atorvastatin treatment attenuated inflammatory infiltration and suppressed the
      increase in TNF-alpha and IFN-gamma levels in EAM mouse hearts. In the whole-cell
      patch-clamp experiment, ventricular cardiomyocyte APD was prolonged in EAM group,
      and atorvastatin blocked this change. We further found that atorvastatin
      attenuated the significant decrease in outward potassium currents in EAM
      myocytes. Our results suggested that atorvastatin may ameliorate EAM progression
      by reducing inflammatory cytokine level. Atorvastatin exerted the antiarrhythmic
      effects by selectively affecting cardiomyocyte ion channel activity and therefore
      improves myocardial repolarization.

PMID- 17217968
TI  - Marine debris accumulation in the Northwestern Hawaiian Islands: an examination
      of rates and processes.
AB  - Large amounts of derelict fishing gear accumulate and cause damage to shallow
      coral reefs of the Northwestern Hawaiian Islands (NWHI). To facilitate
      maintenance of reefs cleaned during 1996-2005 removal efforts, we identify likely
      high-density debris areas by assessing reef characteristics (depth, benthic
      habitat type, and energy regime) that influence sub-regional debris accumulation.
      Previously cleaned backreef and lagoonal reefs at two NWHI locations were
      resurveyed for accumulated debris using two survey methods. Accumulated debris
      densities and weights were found to be greater in lagoonal reef areas. Sample
      weight-based debris densities are extrapolated to similar habitats throughout the
      NWHI using a spatial 'net habitat' dataset created by generalizing IKONOS
      satellite derivatives for depth and habitat classification. Prediction accuracy
      for this dataset is tested using historical debris point data. Annual NWHI debris
      accumulation is estimated to be 52.0 metric tonnes. For planning purposes,
      individual NWHI atolls/reefs are allotted a proportion of this total.

PMID- 17217969
TI  - Fatty acid amide hydrolase inhibitors display broad selectivity and inhibit
      multiple carboxylesterases as off-targets.
AB  - Fatty acid amide hydrolase (FAAH) is the primary regulator of several bioactive
      lipid amides including anandamide. Inhibitors of FAAH are potentially useful for
      the treatment of pain, anxiety, depression, and other nervous system disorders.
      However, FAAH inhibitors must display selectivity for this enzyme relative to the
      numerous other serine hydrolases present in the human proteome in order to be
      therapeutically acceptable. Here we employed activity-based protein profiling
      (ABPP) to assess the selectivity of FAAH inhibitors in multiple rat and human
      tissues. We discovered that some inhibitors, including carbamate compounds SA-47
      and SA-72, and AM404 are exceptionally selective while others, like URB597, BMS
      1, OL-135, and LY2077855 are less selective, displaying multiple off-targets.
      Since proteins around 60kDa constitute the major off-targets for URB597 and
      several other FAAH inhibitors with different chemical structures, we employed the
      multi-dimensional protein identification technology (MudPIT) approach to analyze
      their identities. We identified multiple carboxylesterase isozymes as bona fide
      off-targets of FAAH inhibitors. Consistently, enzymatic assay confirmed
      inhibition of carboxylesterase activities in rat liver by FAAH inhibitors. Since
      carboxylesterases hydrolyze a variety of ester-containing drugs and prodrugs, we
      speculate that certain FAAH inhibitors, by inhibiting carboxylesterases, might
      have drug-drug interactions with other medicines if developed as therapeutic
      agents.

PMID- 17217970
TI  - Camalexin.
AB  - Camalexin (3-thiazol-2'-yl-indole) is the characteristic phytoalexin of
      Arabidopsis thaliana, which is induced by a great variety of plant pathogens.
      While particular pathogens, as well as a human tumour cell line, were growth
      inhibited by camalexin, some fungi show resistance due to active degradation.
      Camalexin originates from tryptophan and its biosynthesis involves the cytochrome
      P450 enzymes CYP79B2 and CYP71B15 (PAD3). Camalexin induction is a complex
      process, for which triggering by reactive oxygen species (ROS), salicylic acid
      signalling, and the glutathione status are important. Targets of the signalling
      cascade are the tryptophan and camalexin biosynthetic genes, which are strongly
      transcriptionally upregulated at the sites of pathogen infection. The important
      knowledge on camalexin, which is reviewed in this paper, will help to establish
      camalexin as a model for the investigation of the significance of phytoalexins in
      response pathogen challenge.

PMID- 17217972
TI  - Maintenance behaviour and long-lasting insecticide-treated nets (LLITNs)
      previously introduced into Bourapar district, Khammouane province, Lao PDR.
AB  - BACKGROUND: Long-lasting insecticide-treated nets (LLITNs) are expected to be an
      important advance in malaria control, but operational experience is still scarce.
      This study presents some operational findings concerning the introduction of
      Olyset LLITNs (Sumitomo Chemical Co., Ltd, Japan) in Laos. The study site,
      Bourapar district, a remote district at high risk of malaria, received Olyset
      nets during 1999-2000. After distribution of the nets the number of malaria cases
      in the district hospital decreased for a time, however it began to rise again a
      year after the intervention. To sustain the effect of the nets, net users were
      given instructions on maintenance and use. This study aimed to investigate the
      condition of Olyset nets and the maintenance behaviour of net users after 2-3
      years of use, and to examine the associations between maintenance behaviour and
      the number of malaria episodes during the previous year. METHODS: Questionnaire
      interviews and inspections of nets were conducted at 240 households during
      February-March 2003. RESULTS: About 40% of the observed nets had holes/were torn,
      and the maintenance instructions had not been followed sufficiently. Households
      following the recommended washing frequency (38.2%) reported fewer malaria
      episodes during the past year, which demonstrates the importance of the
      recommended washing frequency in the effective use of the nets. CONCLUSIONS: Our
      study promotes the idea that, in addition to pursuing high coverage of LLITNs,
      more effort should be made to ensure that nets are kept in good condition in
      future LLITN programmes.

PMID- 17217971
TI  - The impact of political context upon the health policy process in Pakistan.
AB  - BACKGROUND: Analysis of the political context is important for the understanding
      of a health policy and its success, because contextual factors may significantly
      influence the health policy process and health. This article describes how the
      political context in Pakistan influences the health policy process. METHODS: We
      used qualitative research methods based on document analysis and interviews of
      relevant actors in analysing the impact of the political context on the health
      policy process. Document analysis included policy documents and official reports
      of the health ministries, health-related departments and international agencies.
      Interviewees included relevant actors involved in the health policy process at
      local, provincial, national and international levels. RESULTS: Pakistan has
      experienced unbalanced power structures and frequent changes in government, which
      has disturbed health resources and has resulted in a centralized health system
      that hinders wider participation and disrupts health policy-making, planning and
      implementation. CONCLUSION: It is concluded that the political context has had a
      negative influence on the health policy process in Pakistan.

PMID- 17217973
TI  - Critical overview of the management of neonatal jaundice in the UK.
AB  - AIM: To determine the current management of early neonatal jaundice in the UK and
      to evaluate whether the current practices are evidence based. METHODS: A
      questionnaire survey was carried out among identified lead paediatricians of
      neonatal intensive care units. RESULTS: The survey found markedly differing
      practices for the recognition, investigation and treatment of neonatal jaundice.
      This applies particularly to confirmation of the clinical suspicion of jaundice;
      use of invasive and non-invasive technologies for diagnosis; preferred wavelength
      and intensity of light used for treatment; and whether birth weight, gestational
      age and postnatal age should influence treatment. CONCLUSION: The study found a
      lack of consistency in the management of jaundiced infants in the UK. The
      evidence-based practice currently available does not appear to have been
      incorporated into treatment protocols.

PMID- 17217974
TI  - Readability levels of health pamphlets distributed during the Athens 2004 Olympic
      Games.

PMID- 17217975
TI  - Influenza vaccination among persons with chronic respiratory diseases: coverage,
      related factors and time-trend, 1993-2001.
AB  - BACKGROUND: Influenza vaccination has shown itself to be effective in reducing
      morbidity and mortality in patients with underlying chronic respiratory diseases.
      This study sought to: (1) estimate influenza vaccination coverage among asthma
      and chronic bronchitis sufferers; (2) ascertain which variables were associated
      with vaccination; and (3) analyse the time-trend in coverage between 1993 and
      2001. METHODS: This was a descriptive study covering the 2611 subjects included
      in the 1993, 1995, 1997 and 2001 Spanish National Health Surveys who reported
      suffering from asthma or chronic bronchitis. Vaccination coverage was calculated
      for each year and the influence of socio-demographic and health-related variables
      analysed. Using logistic regression, we assessed which of the variables had an
      independent effect on vaccination, and analysed the time-trend. RESULTS: The
      proportions of vaccinated subjects in 1993, 1995-1997 and 2001 were 44.7%, 45.6%
      and 44.4%, respectively. Variables that increased the likelihood of having been
      vaccinated were: higher age, presence of another concomitant chronic disease,
      poor perception of health, non-smoker status, and being married. There was no
      significant variation in coverage over the study period. CONCLUSION: Influenza
      vaccination coverage among Spanish asthma and/or chronic bronchitis sufferers is
      below desirable levels and showed no improvement over the period 1993-2001.
      Implementation of strategies to improve coverage is necessary.

PMID- 17217976
TI  - Effects of cyanobacterial biomass on the Japanese quail.
AB  - Mortality of wild aquatic birds has recently been attributed to cyanobacterial
      toxins. Despite this, no experimental studies on the effects of defined doses of
      microcystins administered orally to birds exist. In this experiment, four groups
      of male Japanese quails daily ingesting 10ml of Microcystis biomass containing
      0.045, 0.459, 4.605 or 46.044mug of microcystins, respectively, for 10 and 30
      days, showed no mortality. Histopathological hepatic changes in birds after the
      biomass exposure included cloudy swelling of hepatocytes, vacuolar dystrophy,
      steatosis and hyperplasia of lymphatic centres. On subcellular level, shrunken
      nuclei of hepatocytes containing ring-like nucleoli, cristolysis within
      mitochondria and vacuoles with pseudomyelin structures were present. Vacuolar
      degeneration of the testicular germinative epithelium was found in two exposed
      males. Statistically significant differences in biochemical parameters were on
      day 10 of exposure only. They comprised increased activities of lactate
      dehydrogenase and a drop in blood glucose in birds receiving the highest dose of
      the biomass. Principal component analysis revealed a pattern of responses in
      biochemical parameters on day 10 that clearly separated the two greatest exposure
      groups from the controls and lower exposures. The results indicate that diagnosis
      of microcystin intoxication solely based on clinical biochemical and
      haematological parameters is hardly possible in birds.

PMID- 17217979
TI  - Aqueous photodegradation and toxicity of the polycyclic aromatic hydrocarbons
      fluorene, dibenzofuran, and dibenzothiophene.
AB  - Decay kinetics resulting from the application of UV and UV/H(2)O(2) to the
      polycyclic aromatic hydrocarbons (PAHs) fluorene, dibenzofuran and
      dibenzothiophene was studied. Batch experiments were conducted with both low
      pressure monochromatic (253.7nm) and medium pressure polychromatic (200-300nm) UV
      sources alone or in the presence of up to 25mg/L hydrogen peroxide, in a quasi
      collimated beam apparatus. Degradation of all three PAHs, by both UV and
      UV/H(2)O(2), exhibited pseudo-first-order reaction kinetics and low quantum
      yields ranging from 1.4x10(-3) to 1.8x10(-2)mol/E using both UV lamps. Toxicity
      testing using a bioluminesence inhibition bioassay was correlated to the decay in
      concentration of the PAHs as analyzed analytically using HPLC. Results
      demonstrated that treatment efficacy of oxidative PAH degradation measured by
      following the decay of the target compound is best complemented by also
      evaluating the toxicity of the treated water due to byproduct formation concerns.

PMID- 17217980
TI  - Exploring temporal variations of oxygen saturation constants of nitrifying
      bacteria.
AB  - Activated sludge models (ASM) are generally accepted as state-of-the-art in
      modeling wastewater treatment plants. In this paper, we assess the temporal
      variability of an ASM parameter-the oxygen half-saturation constant of
      autotrophic bacteria (K(O),(AUT)). A series of respirometric experiments is
      performed for conventional activated sludge and sludge from a membrane
      bioreactor. K(O) values are estimated for both ammonium-oxidizing and nitrite
      oxidizing bacteria. For parameter estimation, the Monod kinetic model structure
      is extended by a sensor model. Still remaining systematic deviations between data
      and model are considered by a thorough residual analysis: (1) uncertainty
      estimates of K(O) are corrected to reflect model structure deficiencies and (2)
      the inter-experimental cross-correlation of residuals is taken into account to
      assess temporal changes. We conclude that K(O),(AUT) is a time variable parameter
      and should be considered accordingly.

PMID- 17217978
TI  - Second-order motion without awareness: passive adaptation to second-order motion
      produces a motion aftereffect.
AB  - Although second-order motion may be detected by early and automatic mechanisms,
      some models suggest that perceiving second-order motion requires higher-order
      processes, such as feature or attentive tracking. These types of attentionally
      mediated mechanisms could explain the motion aftereffect (MAE) perceived in
      dynamic displays after adapting to second-order motion. Here we tested whether
      there is a second-order MAE in the absence of attention or awareness. If
      awareness of motion, mediated by high-level or top-down mechanisms, is necessary
      for the second-order MAE, then there should be no measurable MAE if the ability
      to detect directionality is impaired during adaptation. To eliminate the
      subject's ability to detect directionality of the adapting stimulus, a second
      order drifting Gabor was embedded in a dense array of additional crowding Gabors.
      We found that a significant MAE was perceived even after adaptation to second
      order motion in crowded displays that prevented awareness. The results
      demonstrate that second-order motion can be passively coded in the absence of
      awareness and without top-down attentional control.

PMID- 17217977
TI  - Different mechanisms of antibody-mediated neutralization of parvoviruses revealed
      using the Fab fragments of monoclonal antibodies.
AB  - Antibody binding and neutralization are major host defenses against viruses, yet
      the mechanisms are often not well understood. Eight monoclonal antibodies and
      their Fab fragments were tested for neutralization of canine parvovirus and
      feline panleukopenia virus. All IgGs neutralized >85% of virus infectivity. Two
      Fabs neutralized when present at 5 nM, while the others gave little or no
      neutralization even at 20-100 nM. The antibodies bind two antigenic sites on the
      capsids which overlap the binding site of the host transferrin receptor (TfR).
      There was no specific correlation between Fab binding affinity and
      neutralization. All Fabs reduced capsid binding of virus to purified feline TfR
      in vitro, but the highly neutralizing Fabs were more efficient competitors. All
      partially prevented binding and uptake of capsids by feline TfR on cells. The
      virus appears adapted to allow some infectivity in the presence of at least low
      levels of antibodies.

PMID- 17217981
TI  - Biomass effects on oxygen transfer in membrane bioreactors.
AB  - Ten biomass samples from both municipal and industrial pilot and full scale
      submerged membrane bioreactors (MBRs) with mixed liquor suspended solids
      concentrations (MLSS) ranging from 7.2 to 30.2g L(-1) were studied at six air
      flow rates (0.7, 1.3, 2.3, 3, 4.4 and 6m(3)m(-3)h(-1)). Statistical analyses were
      applied to identify the relative impacts of the various bulk biomass
      characteristics on oxygen transfer. Of the biomass characteristics studied, only
      solids concentration (correlated with viscosity), the carbohydrate fraction of
      the EPS (EPS(c)) and the chemical oxygen demand (COD) concentration of the SMP
      (SMP(COD)) were found to affect the oxygen transfer parameters k(L)a(20) (the
      oxygen transfer coefficient) and alpha-factor. The relative influence on
      k(L)a(20) was MLSS>aeration>EPS(c)>SMP(COD) and on alpha-factor was
      MLSS>SMP(COD)>EPS(c)>aeration. Both k(L)a(20) and alpha-factor increased with
      increasing aeration and EPS(c) and decreased with increasing MLSS and SMP(COD).
      MLSS was found to be the main parameter controlling the oxygen transfer.

PMID- 17217982
TI  - Toxaphene chemistry: separation and characterisation of selected enantiomers of
      the Polychloropinene mixtures.
AB  - The primary goal for the study presented here was the preparation and
      characterisation of enantiomeric pure chlorobornane standards (Toxaphene). In
      this context, we partially modeled the procedure for Polychloropinene production
      in the former USSR. The initial reaction was ionic addition of hydrogen chloride
      to (1S)-alpha-pinene resulting predominantly in (1S)-2-endo-chlorobornane.
      Further photochlorination gave mixtures of chlorinated terpenes with different
      average content of Cl per molecule. The resulting mixtures were separated on a
      silica-gel column and a number of known hepta to decachlorobornanes were
      identified in fractions with the help of NMR and GC (using electron capture and
      mass spectrometric detection)--but in very unusual ratios as compared to the
      technical Toxaphene mixture formerly produced by Hercules (USA). Also several
      previously unknown congeners were isolated or detected. Three of the isolated
      congeners were obtained in crystalline state and X-ray crystallography showed
      their enantiomeric purity.

PMID- 17217983
TI  - Ambient air monitoring of PCDD/Fs and co-PCBs in Gyeonggi-do, Korea.
AB  - We started the monitoring for PCDD/Fs in ambient air and soil in August 2001, and
      co-PCBs in January 2002. Decreasing of PCDD/Fs and co-PCBs levels in ambient air
      were observed. The higher PCDD/Fs levels were found in winter and lower in
      autumn. We found that the industrial incinerators influenced the PCDD/Fs levels
      in ambient air. In the 2,3,7,8-substituted PCDD/Fs concentration profiles, the
      three major congeners occupied 67% of the total mass. In case of co-PCBs,
      PCB#118, #105 and #77 were observed as the main congeners. Five cluster groups
      discriminated by ratio of four components, O(8)CDD, 1,2,3,4,6,7,8-H(7)CDD,
      1,2,3,4,6,7,8-H(7)CDF and O(8)CDF, were obtained from HCA (hierarchical cluster
      analysis).

PMID- 17217984
TI  - Identification of multixenobiotic defence mechanism (MXR) background activities
      in the freshwater bivalve Dreissena polymorpha as reference values for its use as
      biomarker in contaminated ecosystems.
AB  - The biological defence mechanism called MXR or MXD for multixenobiotic resistance
      or defence protects cells against the entry and the accumulation of xenobiotics.
      As the defence is modulated by man made chemicals, MXR is used as a biomarker of
      organisms' exposure to environmental contamination. However, to reliably assess
      and evidence MXR induction, the use of a reference level is required. In this
      context, we focused on MXR background level in a freshwater bivalve, the zebra
      mussel Dreissena polymorpha, in order to propose its use as a reference during
      MXR evaluation. We monitored the MXR transport activity in mussels collected
      either in a natural population or in a caged population and then transplanted to
      clean water in the laboratory. The results showed that MXR activity was decreased
      to its baseline level after an eight to nine day depuration period (13.1+/-3.1;
      7+/-2.6; 13.7+/-3.9 pmol RB min(-1)org(-1) after three experiments of laboratory
      depurations). Moreover, significant MXR induction was measured in depurated zebra
      mussels exposed to contaminated sites (39.6+/-3.7; 59.2+/-20.3 pmol RB min(
      1)org(-1) after two experiments of field exposure), showing that the laboratory
      depuration did not affect the induction potential. The MXR responses (decrease as
      well as increase) occurred in few days and were highly significant, highlighting
      its reactivity in zebra mussels. Finally, this paper confirms the usefulness of
      MXR as a tool in biomonitoring studies and provides a protocol for field
      experiments that enables to establish and use the background level of MXR
      activity as a reference.

PMID- 17217985
TI  - Polycyclic aromatic hydrocarbons in the surface sediments from Yellow River,
      China.
AB  - Fourteen surface sediment samples were collected from Lanzhou Reach of Yellow
      River, China in July 2005. The concentrations of 16 priority polycyclic aromatic
      hydrocarbons (PAHs) were determined by gas chromatography equipped with a mass
      spectrometry detector (GC-MS). Total concentrations of the PAHs ranged from 464
      to 2621 ng/g dry weight. Sediment samples with the highest PAH concentrations
      appeared at the downstream of Lanzhou City, where there was the biggest
      wastewater discharge pipeline from Lanzhou Oil Refinery Factory and Lanzhou
      Chemical Industry Company. Municipal sewage also contributed to the PAH
      contamination in the sediments. A correlation existed between the sediment
      organic carbon content (f(oc)) and the total PAH concentrations (r(2)=0.57),
      suggesting that sediment organic carbon content played an important role in
      controlling the PAHs levels in the sediments. According to the observed molecular
      indices, PAHs contamination in Lanzhou Reach of Yellow River originated both from
      the high-temperature pyrolytic processes and from the petrogenic source, showing
      a mixed PAH input pattern, which was also confirmed by the results of a principal
      component analysis (PCA). According to the numerical effect-based sediment
      quality guidelines (SQGs) of the United States, the levels of PAHs at most
      studied sites in Lanzhou Reach of Yellow River should not exert adverse
      biological effects. Although at some sites (such as S10, S12, etc.) one PAH may
      exceed the effects range low (ERL), individual PAH did not exceed the effects
      range median (ERM). The results indicated that sediments in all sites should have
      potential biological impact, but should have no impairment.

PMID- 17217986
TI  - PCDD/F and dioxin-like PCB in human blood and milk from German mothers.
AB  - Blood samples of pregnant women aged between 19 and 42 years at the time they
      gave birth and milk samples from the same women following delivery were collected
      between September 2000 and January 2003 from 169 participants living in an
      industrialized area of Germany (Duisburg birth cohort study). All samples were
      analyzed for their content of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/F) as well as dioxin-like and indicator polychlorinated biphenyls (PCB).
      Levels of WHO-TEq were in the range of 4.34-97.3 pg/g(lipid base) (median: 26.37,
      arithmetic mean: 28.36) for blood, or 3.01-78.7 pg/g(lipid base) (median: 26.40,
      arithmetic mean: 27.27) for milk, respectively. The four congeners 12378-PeCDD,
      23478-PeCDF, 33'44'5-PeCB (# 126) and 233'44'5-HxCB (# 156) contribute the main
      share to total WHO-TEq. The contribution of PCDD/F in relation to PCB to total
      WHO-TEq was 60:40% in blood and 52:48% in milk. Good correlations of the
      contaminant levels in lipid base between both matrices were found. The
      distribution between blood and milk depends on the molecular weight of the
      substances. Higher chlorinated PCDD/F- and PCB-congeners were found in 2-4-fold
      higher concentrations in blood in relation to milk and the concentrations of
      lower chlorinated PCB-congeners were up to 2-fold higher in milk in relation to
      blood. The body burden of PCDD/F and PCB increases with age and decreases over
      the total nursing period. Women who had lived outside highly industrialized
      countries showed lower concentrations of PCDD/F and PCB. In some cases, elevated
      levels of PCB were observed when the women had previously lived in Eastern Europe
      for a long time. In comparison with recent data, the decline in human PCDD/F and
      PCB levels observed during the nineties seems to have stopped. The individual
      exposures of the infants due to breastfeeding within the first 18 months were
      calculated to be from 4.4 to 318 ng WHO-TEq (median: 106, arithmetic mean: 118).
      The actual mean daily exposure of a breastfed infant can be estimated to 131 pg
      WHO-TEq/kg(body weight).

PMID- 17217987
TI  - Adsorption behavior of 2,4-dichlorophenol and pentachlorophenol in an allophanic
      soil.
AB  - The adsorption of 2,4-dichlorophenol (2,4-DCP) and pentachlorophenol (PCP) by a
      variable-charge soil from southern Chile was studied in a series of batch
      equilibration experiments. 2,4-DCP and PCP adsorption behavior was evaluated as a
      function of pH (pH values of 4.5, 6.0 and 7.5) in a 0.1M KCl (25 degrees C)
      background solution for soil material collected at three different depths (0-20
      cm, 20-40 cm, and 40-60 cm). 2,4-DCP and PCP adsorption decreased with increasing
      soil pH, suggesting that the undissociated species were adsorbed more readily and
      that electrostatic repulsion may inhibit partitioning as pH increases. The PCP
      adsorption was greater than observed for 2,4-DCP and decreased with soil depth.
      Multiple regression analysis between K(d) and various soil properties indicated
      that the soil organic carbon content is a strong indicator of chlorophenol
      adsorption, and in addition to organic carbon, the soil pH is an important
      property controlling adsorption behavior.

PMID- 17217988
TI  - Leachates of municipal solid waste incineration bottom ash from Macao: heavy
      metal concentrations and genotoxicity.
AB  - Heavy metals in municipal solid waste incineration bottom ash (MSWIBA) may leach
      into soil and groundwater and pose long-term risks to the environment. In this
      study, toxicity characteristic leaching procedure (TCLP) was carried out on the
      MSWIBA from Macao. Heavy metals in leachates were determined by inductively
      coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic
      emission spectrometry (ICP-AES), and genotoxicity of leachates was also evaluated
      by micronucleus (MN) assay with Vicia faba root tip cells. The results showed
      that the concentrations of aluminium (Al), manganese (Mn), cobalt (Co), cadmium
      (Cd) and mercury (Hg) in the leachates were less than 0.01 mg l(-1), and those of
      iron (Fe), copper (Cu) and molybdenum (Mo) were less than 0.1 mg l(-1). The
      concentrations of chromium (Cr), zinc (Zn), selemium (Se), strontium (Sr), barium
      (Ba) and caesium (Cs) were between 0.11 mg l(-1) and 2.19 mg l(-1). Lead (Pb)
      concentrations, in particular, reached as high as 19.6 mg l(-1), significantly
      exceeding the maximum concentration limit (5 mg l(-1) for lead by TCLP). Compared
      with the negative group, a significant increase of MN frequencies was observed in
      the leachate-exposed groups (P<0.05). With the increase of heavy metals in the
      leachates, the toxic effects on the Vicia faba root tip cells increased, implying
      that heavy metals were the main factors causing the genotoxic effects. Our
      results suggested that apart from chemical analysis, bioassays like the MN assay
      of Vicia faba root tip cells should also be included in a battery of tests to
      assess the eco-environmental risks of bottom ashes before decisions can be made
      on the utilization, treatment or disposal.

PMID- 17217989
TI  - A new simple method with high precision for determining the toxicity of
      antifouling paints on brine shrimp larvae (Artemia): first results.
AB  - The use of antifouling paints is the only truly effective method for the
      protection of underwater structures from the development of fouling organisms. In
      the present study, the surface to volume concept constitutes the basis for the
      development of a new and improved method for determining the toxicity of
      antifouling paints on marine organisms. Particular emphasis is placed on the
      attainment of a standardized uniformity of coated surfaces. Failure to control
      the thickness of the coat of paint in previous studies of this type, has led to
      inaccurate evaluation of the relative toxicity of samples. Herein, an attempt is
      made to solve this problem using a simple technique which gives completely
      uniform and smooth surfaces. The effectiveness of this technique is assessed
      through two series of experiments using two different types of test containers:
      50 ml modified syringes and 7 ml multiwells. The results of the toxicity
      experiments follow a normal distribution around the average value which allows to
      consider these values as reliable for comparison of the level of toxic effect
      detected with the two types of test containers. The mean lethal concentration
      L(S/V)(50) in the test series conducted in the multiwells (20.38 mm(2)ml(-1))
      does not differ significantly from that obtained in the test series using
      modified syringes (20.065 mm(2)ml(-1)). It can thus be concluded from this
      preliminary study that the new method and the two different ways of exposing the
      test organisms to the antifouling paints and their leachates gave reliable and
      replicable results.

PMID- 17217990
TI  - Polychlorinated biphenyls in sediments of the Tam Giang-Cau Hai Lagoon, Central
      Vietnam.
AB  - The Tam Giang-Cau Hai Lagoon, the largest in south east Asia, suffers from a
      great anthropogenic pressure and appears subject to a process of progressive
      environmental deterioration. To establish causes, history and trends of lagoon
      contamination, sediment samples representing three major parts of the systems
      were sampled and analysed for porosity, organic carbon, total nitrogen,
      delta(13)C, grain size, radiotracers and PCBs. PCB surficial concentrations range
      from 10.2 to 24.5 microg kg(-1), and maximum values are close to NOAA ERL
      guidelines. The downcore distribution of PCBs shows two well defined peaks in the
      core from Tam Giang (25.5 and 16.2 microg kg(-1)), whereas the sediment from Cau
      Hai is characterised by a maximum at the surface. Therefore, present trends
      indicate that contamination is still increasing or slightly decreasing. The
      prevailing congeners are 3-CB and 4-CB, hence recent PCBs appear to be mostly
      originated by Aroclor 1016- and 1242-like mixtures, with some samples influenced
      also by Aroclor 1248. Present sources seem to be similar everywhere and probably
      they are widespread all over the territory of the Thua Thien-Hue province.

PMID- 17217991
TI  - Characterization of a simple bacterial consortium for effective treatment of
      wastewaters with reactive dyes and Cr(VI).
AB  - A microbial consortia consisting of three bacteria isolated from tanning and
      textile wastewaters revealed high capacity to simultaneously bioaccumulate dye
      and Cr(VI). The identity of the bacteria were determined by 16S rRNA gene
      analysis to be closely related to Ochrobactrium sp., Salmonella enterica and
      Pseudomonas aeruginosa. Dependence of initial pH values and range of
      concentrations of the dye Reactive Black B (33.2-103.1 mg l(-1)) and Cr(VI) (19.9
      127.6 mg l(-1)) were examined to find the effect of pH on the dye and Cr(VI)
      bioaccumulation. Optimal pH for growth of the consortia in media containing 35 mg
      l(-1) dye and 50 mg l(-1) Cr(VI) was determined to be around 8. The Cr(VI)
      bioaccumulation by the consortia was rapid in media containing molasses with or
      without reactive dye with a maximum Cr(VI) bioaccumulation yield ranging from 90%
      to 99% within a 2-4d period. A slightly lower yield for the dye bioaccumulation
      was measured with a maximum dye bioaccumulation of 80% at 59.3 mg l(-1) dye and
      69.8 mg l(-1) Cr(VI). The highest specific Cr uptake value was obtained as 76.7
      mg g(-1) at 117.1 mg l(-1) Cr(VI) and 50.8 mg l(-1) dye concentration. This
      ability to bioaccumulate dye and Cr(VI) was more efficient than the enriched
      sludge from which they were isolated.

PMID- 17217992
TI  - Environmental monitoring by gene expression biomarkers in Barbus graellsii:
      laboratory and field studies.
AB  - Barbel (Barbus graellsii) is a freshwater fish used as a sentinel species in
      environmental monitoring programmes and ecotoxicological studies in northern
      Spain, particularly in the Ebro River basin, the largest freshwater resource in
      Spain. We developed specific primers for the quantification of CYP1A and
      metallothionein (MT)-1 and -2 gene expression by QRT-PCR in barbel in order to
      assess their suitability in biological effect monitoring of dioxin-like compounds
      and metals. All three genes responded as expected in laboratory tests, using
      model inducers. Hepatic CYP1A mRNA levels showed a twofold induction in fish
      injected intraperitoneally with beta-naphthoflavone, whereas MT-1 and MT-2 gene
      expression was strongly induced by cadmium (15- and 13-fold, respectively) and
      mercury (five- and eightfold). Barbel populations from different sites on the
      Ebro River basin showed a good correlation between the historical records of
      organochlorine pollution, CYP1A expression levels and EROD activity.
      Nevertheless, although metallothionein protein levels in the liver of wild fish
      correlated with hepatic levels of mercury, MT-1 and MT-2 gene expression did not
      correlate with the mercury content or with the concentration of metals in
      sediments from the sites inhabited by the fish. These results demonstrate the
      utility of barbel CYP1A-mRNA expression, but not that of MT-1 or MT-2, as a
      biomarker in field studies. The tools and protocols developed here are likely to
      apply to other species of the genus Barbus, with some 700 species distributed
      throughout most of the Old World.

PMID- 17217993
TI  - Inactivation of Escherichia coli in the electrochemical disinfection process
      using a Pt anode.
AB  - Recently, the electrochemical disinfection has gained a great interest as one of
      the alternatives to conventional chlorination due to its high effectiveness and
      environmental compatibility. Despite the extensive reports on electro
      chlorination disinfection, few researches were reported on the systems without
      generating chlorine. This study mainly focused on the potential disinfecting
      ability of electro-generated oxidants other than chlorine with using an inert
      medium (chloride-free phosphate buffer solution), which was intended to exclude
      the formation of chlorine during the electrolysis, as the Escherichia coli as an
      indicator bacterium was disinfected by applying the current to a platinum anode.
      The electrochemical inactivation of E. coli without chlorine production was
      demonstrated to occur in two distinct stages. The first stage inactivation takes
      place rapidly at the beginning of electrolysis, which appears to be achieved by
      the electrosorption of negatively charged E. coli cells to the anode surface,
      followed by a direct electron transfer reaction. As the electrolysis continues
      further, the inactivation becomes slower but steady, in contrast to the first
      stage of inactivation. This was attributed to the action of reactive oxidants
      generated from water discharge, such as hydroxyl radical. Overall, this study
      suggests that the electrochemical disinfection could be successfully performed
      even without producing chlorine, recommending the potential application for
      disinfecting water that does not allow including any chloride ions (such as the
      production of ultra-pure sterilized water for semiconductor washing).

PMID- 17217994
TI  - FOXG1 is overexpressed in hepatoblastoma.
AB  - Bacterial artificial chromosome array comparative genomic hybridization analysis
      of hepatoblastomas reveals a deletion in the 14q12 locus in 12 of 16 cases. A
      high frequency of copy gain is seen on chromosomes 1q, 2, 5p, 8, and 20. Frequent
      deletions are also seen at 6q, 17q, and 1p with less frequent gains on 4p, 6p,
      and 19p. 14q12 deletion locus analyses using quantitative real-time polymerase
      chain reaction reveals copy number gain/amplification in the region immediately
      telomeric to the deleted locus, including copy number gain (2- to 4-fold) of
      FOXG1 in 13 out of 16 tumors. This is associated with up-regulation
      (approximately 87-fold) of FOXG1 gene transcripts and increased protein
      expression. Immunostaining reveals an inverse relationship between FOXG1
      expression and p21cip1 expression in all histologic subtypes. However, FOXG1
      transcript levels were significantly higher (approximately 75-fold) in tumors
      with embryonal and small cell components when compared with pure fetal
      hepatoblastomas. FOXG1 has been implicated in the repression of transforming
      growth factor beta-induced expression of p21cip1 and cytostasis. Our findings are
      consistent with such a role for FOXG1. We propose that FOXG1 overexpression may
      contribute to the maintenance of the undifferentiated state in hepatoblastomas
      and could be a potential target for molecular therapeutics. This is the first
      report of a possible role for FOXG1 in hepatoblastoma and pediatric neoplasia.

PMID- 17217995
TI  - Androgen receptor amplification is associated with increased cell proliferation
      in prostate cancer.
AB  - Mechanisms of prostate cancer progression during hormonal therapy and the
      pathobiologic consequences of androgen receptor (AR) gene amplification are
      inadequately known. To further investigate the hypothesis that AR gene
      amplification is associated with increased cell proliferation, we analyzed 123
      paraffin-embedded prostate cancer specimens from men who experienced tumor
      relapse during androgen withdrawal therapy. We used fluorescence in situ
      hybridization to quantify AR gene copy number and Ki-67 immunohistochemistry to
      determine cell proliferation. One third of the tumors showed AR gene
      amplification. Among tumors with AR amplification, the mean cell proliferation
      rate was 19.8 (SD, 12.3; 95% confidence interval [CI], 15.4-24.1), whereas it was
      13.0 (SD, 15.9; 95% CI, 9.1-16.8) in tumors without amplification (P = .032). In
      the best fitting logistic regression model, only proliferation remained
      significant (P = .040). When the median Ki-67 labeling index (6.7%) of all tumors
      was used as a cutoff point, the tumors with AR amplification were more frequently
      highly proliferating than tumors with no amplification (P = .010; odds ratio,
      3.4; 95% CI, 1.4-8.3). Our results imply that progression of prostate cancer
      during androgen withdrawal therapy is associated with AR gene amplification and
      increased cell proliferation rate in one third of tumors. We suggest that AR gene
      amplification is an important molecular mechanism underlying the increase in
      proliferation rate of a substantial fraction of recurrent prostate carcinomas.
      However, efforts should be targeted to develop prostate cancer cell lines to
      study causal relationships between AR gene amplification and various biologic
      variables.

PMID- 17217996
TI  - Orbital marginal zone lymphomas: an immunohistochemical, polymerase chain
      reaction, and fluorescence in situ hybridization study.
AB  - Many studies have been performed on chromosomal aberrations of extranodal
      marginal zone lymphomas. However, only a few have been published so far on ocular
      adnexal marginal zone lymphomas. We studied 18 cases of orbital lymphoid cell
      infiltrates. Using fluorescence in situ hybridization (FISH), we studied some of
      the most common chromosomal aberrations found in extranodal marginal zone
      lymphomas as: trisomies 3, and rearrangements of the 18q21 MALTI gene to detect
      the translocations t(11;18)(q21;q21) and t(14;18)(q32;q21)MALT1. Our goals were
      as follows: (1) study those aberrations in our material and compare them with the
      literature, (2) check their prognostic significance, and (3) check whether
      studying those aberrations with FISH can be used as a diagnostic tool to
      differentiate reactive from neoplastic infiltrates, in addition to
      immunohistochemistry and polymerase chain reaction. We found a high frequency of
      trisomies 3 (68%) and 18 (56.6%), the highest published so far in orbital
      lymphomas. On the other hand, no rearrangement was seen in any of our cases. The
      histologic picture and the clinical course were the same when there was one or
      more aberrations. As for the diagnostic significance, the presence of a prior,
      concurrent, or subsequent lymphoma in almost all the positive for aberrations
      cases suggests that either the orbital infiltrates in these cases are lymphomas,
      or they have, at least, a malignant potential or a genetic instability.
      Therefore, the demonstration of these numerical aberrations by FISH may be an
      additional sensitive, reliable, and relatively simple tool to differentiate
      reactive from neoplastic orbital lymphoid cell infiltrates when the
      immunohistochemistry and polymerase chain reaction, performed in a busy and
      routine-based histopathology laboratory, are unsatisfactory.

PMID- 17217997
TI  - Influence of flooding, salinity and inundation time on the bioavailability of
      metals in wetlands.
AB  - Controlled flooding of lowlands is considered as a potential water management
      strategy to minimize the risk of flooding of inhabited areas during high water
      periods. However, due to industrial activities, river water, sediments and soils
      are often contaminated with metals which may have adverse effects on the
      ecosystem's structure and functioning. Additionally, salinity may greatly affect
      the bioavailability and toxicity of metals present or imported into these
      systems. The effect of contaminated soils under different flooding and salinity
      exposure scenarios on the growth, reproduction and metal accumulation in the
      oligochaete Tubifex tubifex (Muller, 1774) were examined. In these bioassays
      metal contaminated soils were flooded with water of different salinities (0 and 3
      psu), and tested after 0, 6 and 12 months of permanent inundation. We indeed
      found that inundation time had significant decreasing effects on Cu and Zn
      accumulation; although initial accumulation of Cu and Zn was higher in the
      previously unflooded soil at the start of the flooding treatment, these
      differences seem to disappear after 6 months of permanent inundation. Moreover,
      the complex interaction between substrate type and salinity suggests that redox
      potential is probably of major importance.

PMID- 17217998
TI  - Myriophyllum alterniflorum DC., biomonitor of metal pollution and water quality.
      Sorption/accumulation capacities and photosynthetic pigments composition changes
      after copper and cadmium exposure.
AB  - Watermilfoil genus Myriophyllum could be used in ecological surveys as in-situ
      biomonitors of metal pollution and water quality due to its ability to accumulate
      chemicals. The copper and cadmium sorption characteristics of Myriophyllum
      alterniflorum have been investigated. The Langmuir and Freundlich isotherms were
      used to model the metal sorption isotherms and the monolayer sorption capacities,
      as obtained by the Langmuir isotherm, were determined to be 13.9 mg/g and 11.1
      mg/g for Cu2+ and Cd2+ respectively. Results have been compared with previous
      works on watermilfoils and are in accordance with those obtained on Myriophyllum
      spicatum. The sorption of the two metals was time-dependent and the kinetics
      fitted the pseudo-second-order equation well. The data were discussed in terms of
      ionic radii and HSAB concept. The phytotoxic effects assessed by classical (i.e.
      changes in biomass, node length) and photosynthetic pigments content endpoints
      have been investigated using chemometric techniques leading to an effect of
      cadmium onto photosynthetic pigments.

PMID- 17218000
TI  - Dialysis of boar semen prior to freezing-thawing: its effects on post-thaw sperm
      characteristics.
AB  - Low-molecular weight components of the seminal plasma have a detrimental effect
      on sperm function. The present study was undertaken to evaluate the effect of the
      removal of low-molecular weight components by dialysis on sperm characteristics
      prior to and after freezing. Semen, collected from 5 boars, was extended in
      Kortowo-3 extender (K-3, Poland) and cooled for 3h (control non-dialysis) or
      dialyzed for 5h in semi-permeable dialysis bags of 12-14kDa molecular weight cut
      off prior to freezing. The semen samples were diluted in lactose-hen egg yolk
      glycerol extender (lactose-HEY-G) or lactose-lyophilized lipoprotein fractions
      glycerol extender (lactose-LPFo-G), packaged into aluminum tubes and frozen in a
      controlled programmable freezer. Pre-frozen and frozen-thawed spermatozoa were
      evaluated for motility, plasma membrane (SYBR-14 and propidium iodide) and
      acrosome integrity, mitochondrial function (Rhodamine 123) and ATP content. The
      results of the study showed that dialysis significantly improved the sperm
      characteristics prior to freezing. Dialysis enhanced (P<0.05) post-thaw sperm
      motility, plasma membrane integrity and mitochondrial function, but had no
      significant effect (P>0.05) on recovery of spermatozoa with intact acrosomes.
      Furthermore, dialyzed spermatozoa exhibited higher (P<0.05) ATP content compared
      with the control after freezing-thawing. Consistent inter-boar variability was
      detected mainly in dialyzed semen following freezing-thawing. These results
      indicated that the improvement in sperm quality characteristics prior to freezing
      and the post-thaw sperm recovery were due to the removal of low-molecular weight
      components from the seminal plasma. It can be suggested that dialysis is
      effective in improving the post-thaw quality of boar spermatozoa and has also
      great practical importance in improving the protocols for cryopreservation of
      semen. Dialysis may also contribute to a better understanding of different
      mechanisms underlying cryo-induced damage to boar spermatozoa.

PMID- 17217999
TI  - Sex differences in locomotor effects of morphine in the rat.
AB  - Sex differences in reinforcing, analgesic and other effects of opioids have been
      demonstrated; however, the extent to which sex differences in motoric effects of
      opioids contribute to apparent sex differences in their primary effects is not
      known. The goal of this study was to compare the effects of the prototypic mu
      opioid agonist morphine on locomotor activity in male vs. female rats. Saline or
      morphine (1-10 mg/kg) was administered s.c. to adult Sprague-Dawley rats, which
      were placed into a photobeam apparatus for 3-5 h to measure activity. Modulation
      of morphine's effects by gonadal hormones and by handling (either during the test
      session or for 4 days before the test session) were examined. Morphine initially
      suppressed and later increased locomotor activity in both sexes relative to their
      saline-injected controls, but males were more sensitive than females to the
      initial locomotor suppressant effect of morphine. Intermittent, brief handling
      during the 3-h test session blunted morphine-induced locomotor activation in both
      sexes. Females in proestrus were the most sensitive to morphine's locomotor
      stimulant effect, with females in estrus showing the least response to morphine.
      Gonadectomized (GDX) males with or without testosterone were equally sensitive to
      morphine's effects, whereas GDX females treated with estradiol showed a blunted
      response to morphine's effects, similar to intact females in estrus. Brief
      handling on each of 4 consecutive days pre-test attenuated morphine's locomotor
      suppressant effect in males but had no effect in females, thereby eliminating the
      sex difference. These data suggest that sex differences in morphine's effects on
      locomotor activity can be attributed to gonadal hormones in females, and to
      differential stress-induced modulation of morphine's effects in males vs.
      females.

PMID- 17218001
TI  - Neural correlates for learning to read Roman numerals.
AB  - This study examined the neuronal correlates of reading Roman numerals and the
      changes that occur with extensive practice. Subjects were scanned by functional
      Magnetic Resonance Imaging (fMRI) three times the first day of the experiment and
      once following two to three months of practice. This allowed comparison of brain
      activations with varying levels of practice on the same day and across the two to
      three months of training. The results revealed that upon learning that the
      alphabetical symbols had numeric meaning subjects immediately activated a network
      of brain areas, many of which have been previously implicated in numerical
      processing. Subsequent practice led to a change in the pattern of neuronal
      activity in only a single region of the mid-dorsolateral prefrontal cortex in the
      left hemisphere. Implications of these findings are argued with regard to the
      prevalent neuronal model for the implementation of elementary numerical
      abilities.

PMID- 17218002
TI  - Dendritic copolymers and particulate filler composites for dental applications:
      degree of conversion and thermal properties.
AB  - OBJECTIVES: The aim of this study was to determine the degree of double bond
      conversion and thermal properties of photopolymerized dendritic copolymers and
      particulate filler composites that may be used as dental restorative materials.
      METHODS: The resins consisted of a multifunctional dendritic monomer, methyl
      methacrylate and varying proportions of acetoacetoxyethyl methacrylate. In
      addition, one of the composites contained 1,4-butanediol dimethacrylate.
      Camphorquinone and 2-(N,N-dimethylamino)ethyl methacrylate were used as the light
      activated initiation system. The degree of conversion was determined with Fourier
      transform infrared spectroscopy and the thermal properties with differential
      scanning calorimetry. RESULTS: The degree of conversion of copolymers varied from
      52 to 60% and increased with increasing concentration of acetoacetoxyethyl
      methacrylate. The values for the composites were 32-44%. Reaction exotherms of
      0.2-9.6J/g were measured for the photopolymerized experimental materials
      indicating residual reactivity that increased with increasing concentration of
      acetoacetoxyethyl methacrylate. The residual reactivity trend seemed counter
      intuitive to the degree of conversion. The glass transition temperatures for the
      completely polymerized copolymers containing acetoacetoxyethyl methacrylate were
      112-116 degrees C and for the particulate filler composites 84-87 degrees C.
      SIGNIFICANCE: The addition of acetoacetoxyethyl methacrylate increased the degree
      of conversion. The polymerization characteristics of the experimental materials
      were comparable to those of control materials.

PMID- 17218003
TI  - Brief report: how do adolescents perceive the risks related to cell-phone use?
AB  - Besides the social risks of incivility and impoliteness (I-incivility), cell
      phone use is classically associated with two types of physical risk: microwave
      radiation (LIMRadiation) and decreased attention while driving (CPUWDriving). As
      the literature has showed that adolescents' risky behavior was consistent with
      their risk perception, we ran a self-report survey to evaluate 1/how French
      adolescents (n=1129) perceived physical risks related to CPUWDriving, exposure to
      LIMRadiation, and social risks related to I-incivility; and 2/the factors
      underlying these risk perceptions. Results showed that adolescents have an acute
      perception of the risks associated with CPUWDriving and appeared to be concerned,
      as a whole, with social risks related to I-Incivility. They do not appear
      particularly concerned by the risks related to LIMRadiation, which may reflect
      societal confusion about risks still considered as hypothetical and/or based on
      equivocal evidence. Gender, ethnicity, and age were not predictive for perceived
      risks. Level of schooling had a positive influence on perceived risks related to
      CPUWDriving and I-Incivility, and cell-phone ownership had an inverse
      relationship with perceived risks related to I-Incivility.

PMID- 17218004
TI  - Brief report: the theory of planned behaviour applied to physical activity in
      young people who smoke.
AB  - It has been hypothesised that physical activity may be useful as a smoking
      cessation intervention for young adults. In order to inform such interventions,
      this study evaluated the theory of planned behaviour (TPB) for understanding
      physical activity behaviour in young smokers. Regular smokers aged 16-19 years
      (N=124), self-reported physical activity and all TPB components. Physical
      activity behaviour was significantly explained by both intention and perceived
      behavioural control (PBC), with both intention and PBC making significant
      contributions to the model. Intention was significantly explained by attitude,
      subjective norm (SN) and PBC, with attitude, SN and PBC all making significant
      contributions to the model. The TPB may be a useful framework for guiding
      physical activity interventions among young smokers.

PMID- 17218005
TI  - The regulation of integrin-mediated osteoblast focal adhesion and focal adhesion
      kinase expression by nanoscale topography.
AB  - An important consideration in developing physical biomimetic cell-stimulating
      cues is that the in vivo extracellular milieu includes nanoscale topographic
      interfaces. We investigated nanoscale topography regulation of cell functions
      using human fetal osteoblastic (hFOB) cell culture on poly(l-lactic acid) and
      polystyrene (50/50 w/w) demixed nanoscale pit textures (14, 29, and 45nm deep
      pits). Secondary ion mass spectroscopy revealed that these nanotopographic
      surfaces had similar surface chemistries to that of pure PLLA because of PLLA
      component surface segregation during spin casting. We observed that 14 and 29nm
      deep pit surfaces increased hFOB cell attachment, spreading, selective integrin
      subunit expression (e.g., alphav relative to alpha5, beta1, or beta3), focal
      adhesive paxillin protein synthesis and paxillin colocalization with cytoskeletal
      actin stress fibers, and focal adhesion kinase (FAK) and phosphorylated FAK
      (pY397) expression to a greater degree than did 45nm deep pits or flat PLLA
      surfaces. Considering the important role of integrin-mediated focal adhesion and
      intracellular signaling in anchorage-dependent cell function, our results suggest
      a mechanism by which nanostructured physical signals regulate cell function.
      Modulation of integrin-mediated focal adhesion and related cell signaling by
      altering nanoscale substrate topography will have powerful applications in
      biomaterials science and tissue engineering.

PMID- 17218006
TI  - Reducible poly(amido ethylenimine) directed to enhance RNA interference.
AB  - Designing synthetic macromolecular vehicles with high transfection efficiency and
      low cytotoxicity has been a major interest in the development of non-viral gene
      carriers. A reducible poly(amido ethylenimine) (SS-PAEI) synthesized by addition
      copolymerization of triethylenetetramine and cystamine bis-acrylamide
      (poly(TETA/CBA)) was used as a carrier for small interference RNA (siRNA).
      Poly(TETA/CBA) could efficiently condense siRNA to form stable complexes under
      physiological conditions and perform complete release of siRNA in a reductive
      environment. When formulated with VEGF-directed siRNA, poly(TETA/CBA)
      demonstrated significantly higher suppression of VEGF than linear
      polyethylenimine (PEI) (L-PEI, 25kDa) in human prostate cancer cells (PC-3).
      After 5h of transfection, substantial dissociation and intracellular distribution
      of siRNA was observed in the poly(TETA/CBA) formulation, but not in the L-PEI
      formulation. The triggered release of siRNA by reductive degradation of
      poly(TETA/CBA) in the cytoplasm may affect the RNAi activity by increasing
      cytoplasmic availability of siRNA. These results suggest that the rational design
      of non-viral carriers should involve considerations for intracellular
      dissociation and trafficking of a nucleic acid drug to maximize its effect, in
      conjunction with formation of stable complexes under physiological conditions.

PMID- 17218007
TI  - Synthesis and characterization of electroactive and biodegradable ABA block
      copolymer of polylactide and aniline pentamer.
AB  - A triblock copolymer PLA-b-AP-b-PLA (PAP) of polylactide (PLA) and aniline
      pentamer (AP) with the unique properties of being both electroactive and
      biodegradable is synthesized by coupling an electroactive carboxyl-capped AP with
      two biodegradable bi-hydroxyl-capped PLAs via a condensation reaction. Three
      different molecule weight PAP copolymers are prepared. The PAP copolymers exhibit
      excellent electroactivity similar to the AP and polyaniline, which may stimulate
      cell proliferation and differentiation. The electrical conductivity of the PAP2
      copolymer film ( approximately 5x10(-6)S/cm) is in the semiconducting region.
      Transmission electron microscopic results suggest that there is microphase
      separation of the two block segments in the copolymer, which might contribute to
      the observed conductivity. The biodegradation and biocompatibility experiments in
      vitro prove the copolymer is biodegradable and biocompatible. Moreover, these new
      block copolymer shows good solubility in common organic solvents, leading to the
      system with excellent processibility. These biodegradable PAP copolymers with
      electroactive function thus possess the properties that would be potentially used
      as scaffold materials for neuronal or cardiovascular tissue engineering.

PMID- 17218008
TI  - Expression of cathepsin P mRNA, protein and activity in the rat choriocarcinoma
      cell line, Rcho-1, during giant cell transformation.
AB  - Lysosomal proteases perform critical functions in protein turnover and are
      essential for normal growth and development. Cathepsin P is a member of a newly
      discovered family of lysosomal cysteine proteases uniquely expressed in rodent
      placenta (PECs), and is closely related to human cathepsin L. Using the rat
      choriocarcinoma cell line model, Rcho-1, mRNA for the PECs cathepsins P, M, Q, R,
      1, 2 was found to increase in expression during differentiation into a
      trophoblast giant cell phenotype. By contrast, expression of cathepsin L was not
      regulated. A specific enzyme assay was developed to show that activity of
      cathepsin P mirrored mRNA expression during differentiation. Cathepsin P protein
      co-localizes with cathepsin B, indicating that the enzyme probably functions in
      the endosomal-lysosomal compartment. This study demonstrates that the PEC genes
      produce functional proteases that can perform specific placental roles that are
      probably performed by broader specificity proteases in human placenta.

PMID- 17218009
TI  - Acute atherosis in decidual tissue: not associated with systemic oxidative stress
      in preeclampsia.
AB  - The aim of this study was to explore a possible association between the presence
      of decidual acute atherosis, maternal hyperlipidaemia and oxidative stress in the
      maternal circulation in preeclamptic and uneventful pregnancies. Decidual tissue
      was harvested by a vacuum suction technique following delivery of the baby and
      placenta in 102 caesarean deliveries. Maternal plasma lipid profile and
      concentration of 8-isoprostane, a marker of oxidative stress, was analysed. Acute
      atherosis was present in 42% of the preeclamptic patients with identified spiral
      arteries. CD68 positive foam cells were found in the spiral artery walls in 14%
      of the normal pregnancies. We have previously demonstrated an elevated plasma
      level of 8-isoprostane in the preeclampsia group, as compared to the uneventful
      pregnancy group (218 vs. 354 pg/mL, p=0.02). Presence of acute atherosis was,
      however, not associated with an elevated level of oxidative stress in the
      maternal circulation, measured as 8-isoprostane. In conclusion, the presence of
      decidual vascular changes in the form of acute atherosis is not necessarily
      paralleled by hyperlipidaemia or augmented oxidative stress in the maternal
      systemic circulation. This study adds to the notion of preeclampsia being a
      multifactorial disease with a variety of clinical forms.

PMID- 17218010
TI  - Balance of NF-kappaB and p38 MAPK is a determinant of radiosensitivity of the AML
      2 and its doxorubicin-resistant cell lines.
AB  - This study investigated radioresistance mechanisms in the doxorubicin-resistant
      acute myelogenous leukemia (AML)-2/DX100. AML-2/DX100 also showed resistance to
      radiation. AML-2/DX100 characterized by down-regulated catalase expression was
      supersensitive to exogenous hydrogen peroxide whereas they increased defense
      mechanisms against endogenous reactive oxygen species (ROS) as compared with AML
      2/WT. In AML-2/WT, radiation increased Bax expression and its translocation to
      mitochondria but had little effect on translocation of Bcl-2 and consequently
      induced the release of cytochrome c from the mitochondria with the subsequent
      caspase-3 activation. On the contrary, in AML-2/DX100, radiation neither
      increased Bax expression nor its translocation to mitochondria while it increased
      Bcl-2 translocation to mitochondria. A specific p38 MAPK inhibitor SB203580
      increased radioresistance in AML-2/WT but little in AML-2/DX100. It inhibited
      radiation-induced Bax translocation in AML-2/WT but not in AML-2/DX100,
      indicating that p38 MAPK is working after irradiation in AML-2/WT but not in AML
      2/DX100. Electrophoretic mobility shift assay and Western blot analysis revealed
      that NF-kappaB in AML-2/DX100 was more activated with degradation of cytosolic
      IkappaBalpha than was that of AML-2/WT. cDNA microarray showed that Bfl-1/A1 and
      granzyme H in AML-2/DX100 were highly up-regulated (6.21-fold) and down-regulated
      (6.49-fold), respectively, as compared with each of AML-2/WT, which were
      confirmed by RT-PCR assay. Taken together, these results indicate that
      radioresistance mechanisms of AML-2/DX100 could be related to alterations in ROS
      scavenging activity, in mitochondrial translocation of Bax and Bcl-2, and in
      expression of pro-apoptotic (granzyme H) and anti-apoptotic (Bfl-1/A1) genes. It
      has been shown that balance of p38 MAPK and NF-kappaB signals is a determinant in
      radiosensitivity of AML-2/WT and AML-2/DX100.

PMID- 17218011
TI  - Characterization of a cryptic plasmid from Bacillus sphaericus strain LP1-G.
AB  - A cryptic plasmid from Bacillus sphaericus strain LP1-G, designated as pLG, was
      sequenced and characterized. It was an 11,066bp circular molecule, with G+C
      content of 37%. The plasmid pLG was predicted to encode 23 putative ORFs, and ORF
      21 shared the highest identity with Rep of pGI1 and pBMB9741, members of rolling
      circle replication (RCR) pC194-family. Sequence analysis revealed a pC194-type
      double strand origin (dso) and a single strand origin (sso) like sequence located
      upstream and downstream of ORF 21, respectively. Moreover, Mung bean nuclease
      analysis and Southern hybridization confirmed the existence of single stranded
      DNA (ssDNA) intermediates, indicating that pLG belongs to the RCR pC194-family.
      Accumulation of multiple ssDNA intermediates in native strain LP1-G and decline
      of ssDNA and supercoiled DNA in rifampicin-treated strain implied that a special
      mechanism might be employed by pLG. Furthermore, the copy number of pLG in its
      original host was determined and about 58 copies of the plasmid exist in each
      cell. Subcloning and transformation experiments proved that the minimal replicon
      of pLG was within a 1.6-kb fragment, which was composed of rep gene and dso.
      These data are a good basis for the understanding of replication mechanisms and
      genetics of this B. sphaericus plasmid.

PMID- 17218012
TI  - pPSX: a novel vector for the cloning and heterologous expression of antitumor
      antibiotic gene clusters.
AB  - A cosmid cloning vector has been constructed that demonstrates high levels of
      segregational stability in Escherichia coli K12. pPSX is a 14-kilobase vector
      derived from the IncW plasmid pR388. pPSX is highly stable in E. coli in the
      absence of antibiotic selection, even while expressing the toxic indolocarbazole
      antitumor antibiotic violacein. The incorporation of the lambdacos sequence
      enables construction of cosmid libraries with inserts ranging from 24 to 36kb.
      The inclusion of a lacZalpha multiple cloning site (MCS) allows blue/white
      screening. pPSX cosmids can be extracted from the host cell with commercial
      plasmid extraction kits facilitating downstream analysis, sequencing and sub
      cloning. pPSX can be transferred to a variety of heterologous hosts by either
      electroporation or mobilization from E. coli S17-1. While it is unstable in non
      E. coli hosts without antibiotic selection, heterologous host strains such as
      Rhodobacter sphaeroides and Pseudomonas stutzeri will maintain the plasmid under
      antibiotic selection to allow screening of expressed inserts. pPSX provides the
      benefits of large insert sizes with high stability to allow cloning of
      chemotherapeutic gene clusters in E. coli and a range of other heterologous
      hosts.

PMID- 17218013
TI  - The use of a metallothionein-like-proteins (MTLP) kinetic approach for metal
      bioavailability monitoring in dredged material.
AB  - Ecotoxicological effects associated with contaminants present in dredged material
      from Spain were determined using a marine biotest based on the determination of
      metallothionein-like-protein concentrations (MTLPs) in the shore crab Carcinus
      maenas. Intermoult female C. maenas were exposed in the laboratory to sediments
      from three Spanish ports, Ria de Huelva (SW, Spain), La Coruna (NW, Spain) and
      Bahia de Cadiz (SW, Spain) per replicate during 21 days. Hepatopancreas samples
      from crabs were taken for metallothioneins analysis on days 0, 7 and 21.
      Furthermore, chemical analysis was performed in the stations to determine the
      degree and nature of sediment contamination (Cr, Ni, Cu, Zn, Cd, Pb, Hg, As, PAHs
      and PCBs). A significant increase (p<0.05) in metallothionein concentration was
      observed over time in individuals exposed to sediment from the port Ria de Huelva
      characterized by high concentrations of metals. A toxicokinetic approach is
      proposed in this study related to the use of this biomarker in C. maenas to
      evaluate bioavailability associated with metals present in dredged material. As a
      first step, this toxicokinetic approach might reveal as a sensitive tool for
      evaluating bioavailability of contaminants present in dredged material.

PMID- 17218014
TI  - Chromatin accessibility and epigenetic modifications differ between frequently
      and infrequently rearranging VH genes.
AB  - The molecular mechanisms that control the temporal and lineage-specific
      accessibility, as well as the rearrangement frequency of V(H) genes for V(H)-to
      DJ(H) recombination, are not fully understood. We previously found a positive
      correlation between the extent of histone acetylation and the differential
      rearrangement frequency of individual V(H) genes. Here, we demonstrated that
      poorly rearranging V(H) genes are more highly associated with histone H3
      dimethylated at lysine 9, a marker of repressive chromatin, than frequently
      rearranging V(H) genes. We also observed a positive relationship between the
      differential binding of Pax5 to individual V(H)S107 genes and rearrangement
      frequency. Furthermore, we showed that accessibility of the regions flanking the
      Pax5 binding site and the recombination signal sequence (RSS) to restriction
      enzyme cleavage correspond with the differential rearrangement frequency of the
      V(H)S107 family members. In addition, we found that the CpG sites located in the
      coding regions of V(H) genes are methylated in general, while the extent of DNA
      methylation drops dramatically near the RSS. For the V(H)S107 family, one CpG
      site located 101bp upstream of the RSS showed variable methylation that
      correlates with rearrangement frequency, and the methylation status of a CpG site
      located 34bp downstream of the RSS could also favor the rearrangement of V1 over
      V11. These findings suggest that the extent of histone modifications, chromatin
      accessibility, DNA methylation, as well as the differential binding of Pax5 to
      V(H) coding regions, could all influence the rearrangement frequency of
      individual V(H) genes, although some of these mechanisms are not strictly B cell
      specific.

PMID- 17218015
TI  - Preparation of highly efficient monolithic silica capillary columns for the
      separations in weak cation-exchange and HILIC modes.
AB  - Weak cation-exchange (WCX) and HILIC modes columns were prepared by on-column
      polymerization of acrylic acid on monolithic silica capillary columns modified
      with N-(3-triethoxysilylpropyl)methacrylamide anchor groups. The polymer-coated
      columns could be used for HILIC mode separation of pyridylamino (PA)-sugars and
      peptides including a tryptic digest of BSA, while for weak cation-exchange mode
      for the separation of proteins and nucleosides even at high linear velocity. The
      poly(acrylic acid) coated monolithic silica capillary columns showed greater
      retention toward PA-sugars than a polyacrylamide coated monolithic silica
      capillary columns prepared in the same manner. Proteins and nucleosides were
      separated effectively at pH 6.9 using the same column. The column provided fair
      permeability after the polymer-coating step. High-speed separation of proteins at
      u=4.66 mm/s with high efficiency was shown to be possible, while high-speed
      separation of nucleosides has achieved within one minute using the column at
      u=8.67 mm/s, suggesting that the column will be suitable for the second dimension
      separation of multidimensional HPLC systems.

PMID- 17218016
TI  - IL-18 deficiency inhibits both Th1 and Th2 cytokine production but not the
      clinical symptoms in experimental autoimmune neuritis.
AB  - IL-18 deficient (IL-18-/-) mice were used to investigate the role of IL-18 in the
      pathogenesis of experimental autoimmune neuritis (EAN) which was induced by
      immunization of the mice with P0 protein peptide 180-199. The clinical course was
      not different between IL-18-/- and wild-type mice. The splenic mononuclear cell
      (MNC) proliferation was also similar in both animal groups. However, the
      percentages of IFN-gamma, IL-10 and IL-12 positive cells were decreased among
      infiltrating MNC of cauda equine in IL-18-/- mice. This indicates that IL-18
      deficiency inhibits the production of both Th1 and Th2 cytokines in the target
      organ of mice with EAN.

PMID- 17218017
TI  - Herbal medicines to treat Alzheimer's disease.

PMID- 17218018
TI  - PKC signaling deficits: a mechanistic hypothesis for the origins of Alzheimer's
      disease.
AB  - There is strong evidence that protein kinase C (PKC) isozyme signaling pathways
      are causally involved in associative memory storage. Other observations have
      indicated that PKC signaling pathways regulate important molecular events in the
      neurodegenerative pathophysiology of Alzheimer's disease (AD), which is a
      progressive dementia that is characterized by loss of recent memory. This
      parallel involvement of PKC signaling in both memory and neurodegeneration
      indicates a common basis for the origins of both the symptoms and the pathology
      of AD. Here, we discuss this conceptual framework as a basis for an autopsy
      validated peripheral biomarker--and for AD drug design targeting drugs
      (bryostatin and bryologs) that activate PKC isozymes--that has already
      demonstrated significant promise for treating both AD neurodegeneration and its
      symptomatic memory loss.

PMID- 17218019
TI  - GDNF family receptor complexes are emerging drug targets.
AB  - Glial-cell-line-derived neurotrophic factor (GDNF) family ligands (GFLs), which
      consist of GDNF, neurturin, artemin and persephin, regulate the development and
      maintenance of the nervous system. GDNF protects and repairs dopamine-containing
      neurons, which degenerate in Parkinson's disease, and motoneurons, which die in
      amyotrophic lateral sclerosis. GDNF and neurturin have shown promise in clinical
      trials of Parkinson's disease, and artemin is currently undergoing clinical
      trials for chronic pain treatment. However, the delivery of GFLs into the brain
      through invasive approaches such as neurosurgery, viral vectors or by the use of
      encapsulated cells is associated with multiple obstacles. The development of
      small molecules that specifically activate GFL receptors and that can be applied
      systemically would overcome most of these problems. The unique nature of the GFL
      receptors, recent progress in elucidation of the 3D structures of GFLs and GFL
      receptor complexes and the use of high-throughput screening have resulted in the
      development of the first small molecules that mimic the effects of the different
      GFLs.

PMID- 17218020
TI  - Simultaneous detection of five different DNA targets by real-time Taqman PCR
      using the Roche LightCycler480: Application in viral molecular diagnostics.
AB  - One of the most interesting aspects of real-time PCR based on the detection of
      fluorophoric labeled oligonucleotides is the possibility of being able to detect
      conveniently multiple targets in the same PCR reaction. Recently, Roche
      Diagnostics launched a real-time PCR platform, the LightCycler480 (LC480), which
      should be well suited for multiplex real-time PCR analysis. In this paper the
      performance of the LC480 and accompanying software for the detection of five
      different targets was analyzed. Target DNAs mixed at equimolar concentrations
      were detected reproducibly and quantitatively. In addition, mixing different
      concentrations of the five targets demonstrated that the LC480 is capable of
      providing quantitative results for a mixture of DNA sequences without losing
      sensitivity. When applied to the practice of molecular diagnosis of four
      respiratory viral infections the multiplex assay showed almost complete
      concordance with corresponding single-target PCRs. The application of multiplex
      PCR for the detection of multiple pathogens within the same sample will provide a
      major contribution to the efficiency, logistics and cost-effectiveness of
      molecular diagnostics.

PMID- 17218021
TI  - Rapid diagnosis of H5N1 avian influenza virus infection by newly developed
      influenza H5 hemagglutinin gene-specific loop-mediated isothermal amplification
      method.
AB  - Reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) is a
      unique gene amplification method that can be completed within 35 min at 62.5
      degrees C. In the present study, RT-LAMP was used to develop a rapid and
      sensitive laboratory diagnostic system for the H5N1 highly pathogenic avian
      influenza (HPAI). The sensitivity of the system was 0.1-0.01 plaque-forming units
      per reaction for HPAI-H5N1 viruses belonging to the genetically and antigenically
      distinct clade 1, represented by A/Vietnam/JP1203/2004, and clade 2, represented
      by A/Indonesia/JP283/2006. This RT-LAMP sensitivity is 10-fold higher than the
      sensitivity of standard one-step RT-PCR. By using viral RNAs extracted from avian
      influenza viruses of H1-H15 hemagglutinin (HA) subtypes and human pathogenic
      respiratory viruses, it was confirmed that the RT-LAMP system amplifies
      specifically RNA of the H5 subtype virus. The system detected H5-HA genes in
      throat swabs collected from humans as well as from wild birds. These results
      suggest that the present RT-LAMP system is a useful diagnostic tool for
      surveillance of recent outbreaks of the HPAI-H5N1 virus.

PMID- 17218022
TI  - Baculovirus expression of beak and feather disease virus (BFDV) capsid protein
      capable of self-assembly and haemagglutination.
AB  - Beak and feather disease virus (BFDV) is a common avian circovirus infection of
      wild Psittaciformes and is a recognised threat to endangered psittacine species.
      Currently, there is a requirement to develop BFDV antigen for diagnostic purposes
      and since efforts to propagate BFDV in vitro have so far been unsuccessful the
      entire coding region of BFDV ORF C1 was expressed in Sf9 insect cells using a
      baculovirus expression system. The entire coding region of BFDV ORF C1, the
      presumptive capsid, was expressed in Sf9 insect cells using baculovirus
      expression system. Electron microscopic examination of negatively stained
      material demonstrated that the recombinant protein self-assembled to produce
      virus-like particles (VLPs) thus confirming that ORF C1 is likely to be the sole
      determinant for capsid construction in vivo. BFDV VLPs also possessed
      haemagglutinating activity which provides further evidence that self-assembled
      BFDV VLPs retain receptor mediated biological activity and that the determinants
      for BFDV haemagglutination activity rely solely on the capsid protein. The
      recombinant protein reacted with anti-BFDV sera from naturally immune parrots and
      cockatoo and from chickens experimentally inoculated with native BFDV in both
      Western blots and haemagglutination inhibition (HI) assay. BFDV VLPs were also a
      suitable replacement antigen for serological detection of BFDV antibody by HI.

PMID- 17218024
TI  - Artificial selection on laterality in the teleost fish Girardinus falcatus.
AB  - We performed five generations of artificial selection on laterality of eye
      preference in Girardinus falcatus using a detour test. Two lines were selected
      for right turning when encountering a potential predator, two for left turning,
      one for no turning bias and one unselected line was used as control. We observed
      a prompt response to directional selection in all lines and the response was
      approximately symmetrical in left and right turning lines. However, the response
      to selection ceased after the first or the second generation and unexpectedly in
      all lines the average laterality score slowly decreased in subsequent
      generations. After selection was suspended for three generations, no significant
      variation in mean laterality was observed in most cases, indicating that natural
      selection was not actively opposing artificial selection during the experiment.
      After five generations, selected lines maintained substantial additive variance
      as evidenced by the possibility of rapidly reversing the direction of laterality
      bias in just one generation of counter-selection.

PMID- 17218023
TI  - Impaired spatial working memory and altered choline acetyltransferase (CHAT)
      immunoreactivity and nicotinic receptor binding in rats exposed to intermittent
      hypoxia during sleep.
AB  - Exposure to intermittent hypoxia (IH), such as occurs in sleep-disordered
      breathing (SDB), is associated with cognitive impairment, neurodegeneration,
      oxidative stress, and inflammatory responses within rodent brain regions such as
      the basal forebrain. In this region, damage to cholinergic neurons correlates
      with working memory deficits in a number of neurodegenerative disorders,
      suggesting that degeneration of cholinergic systems may also contribute to the
      working memory impairments observed after IH exposures. We therefore examined
      basal forebrain choline acetyltransferase (CHAT) immunohistochemistry, nicotinic
      receptor binding in the prefrontal cortex (PFC), and working memory, in male rats
      tested on a delayed matching to place (DMP) task in the water maze following
      exposure to either room air (RA) or intermittent hypoxia (IH; alternating 90s
      epochs of 21% and 10% O(2) during sleep). IH-treated animals displayed impaired
      working memory with respect to controls, along with significant reductions in
      CHAT-stained neurons in the medial septal nucleus, in both the vertical and
      horizontal limbs of the diagonal band, and the substantia inominata after 14 days
      of IH exposure. In addition, increases in nicotinic binding and receptor affinity
      in the PFC were observed after 14 days of IH exposure. Thus, a loss of
      cholinergic neuronal phenotype in the basal forebrain may contribute to the
      cognitive impairments associated with CIH exposure. However, compensatory
      mechanisms may also be activated in other brain regions, and may provide
      potential therapeutic targets for the cognitive impairments associated with SDB.

PMID- 17218025
TI  - Phosphoinositide hydrolysis increase by angiotensin-(1--7) in neonatal rat brain.
AB  - Angiotensin (Ang)-(1-7) is an endogenous peptide hormone of the renin-angiotensin
      system which exerts diverse biological actions, some of them counterregulate Ang
      II effects. In the present study potential effect of Ang-(1-7) on
      phosphoinositide (PI) turnover was evaluated in neonatal rat brain. Cerebral
      cortex prisms of seven-day-old rats were preloaded with [(3)H]myoinositol,
      incubated with additions during 30 min and later [(3)H]inositol-phosphates (IPs)
      accumulation quantified. It was observed that PI hydrolysis enhanced 30% to 60%
      in the presence of 0.01 nM to 100 nM Ang-(1-7). Neither 10 nM [D-Ala(7)]Ang-(1
      7), an Ang-(1-7) specific antagonist, nor 10 nM losartan, an angiotensin II type
      1 (AT(1)) receptor antagonist, blocked the effect of 0.1 nM Ang-(1-7) on PI
      metabolism. The effect of 0.1 nM Ang-(1-7) on PI hydrolysis was not reduced but
      it was even significantly increased in the simultaneous presence of [D-Ala(7)]Ang
      (1-7) or losartan. PI turnover enhancement achieved with 0.1 nM Ang-(1-7)
      decreased roughly 30% in the presence of 10 nM PD 123319, an angiotensin II type
      2 (AT(2)) receptor antagonist. The antagonists alone also enhanced PI turnover.
      Present findings showing an increase in PI turnover by Ang-(1-7) represent a
      novel action for this peptide and suggest that it exerts a function in this
      signaling system in neonatal rat brain, an effect involving, at least partially,
      angiotensin AT(2) receptors.

PMID- 17218026
TI  - Activation of paraventricular nucleus of hypothalamus 5-HT1A receptor on sodium
      intake.
AB  - Hypothalamic paraventricular nucleus (PVN) has an important role in the
      regulation of water and sodium intake. Several researches described the presence
      of 5-HT(1) receptors in the central nervous system. 5-HT(1A) was one of the prime
      receptors identified and it is found in the somatodendritic and post-synaptic
      forms. Therefore, the aim of this study was to investigate the participation of
      serotonergic 5-HT(1A) receptors in the PVN on the sodium intake induced by sodium
      depletion followed by 24 h of deprivation (injection of the diuretic furosemide
      plus 24 h of sodium-deficient diet). Rats (280-320 g) were submitted to the
      implant of cannulas bilaterally in the PVN. 5-HT injections (10 and 20 microg/0.2
      microl) in the PVN reduced NaCl 1.8% intake. 8-OH-DPAT injections (2.5 and 5.0
      microg/0.2 microl) in the PVN also reduced NaCl 1.8% intake. pMPPF bilateral
      injections (5-HT(1A) antagonist) previously to 8-OH-DPAT injections have
      completely blocked the inhibitory effect over NaCl 1.8% intake. 5-HT(1A)
      antagonists partially reduced the inhibitory effect of 5-HT on NaCl 1.8% intake
      induced by sodium depletion. In contrast, the intake of palatable solution (2%
      sucrose) under body fluid-replete conditions was not changed after bilateral PVN
      8-OH-DPTA injections. The results show that 5-HT(1A) serotonergic mechanisms in
      the PVN modulate sodium intake induced by sodium loss. The finding that sucrose
      intake was not affected by PVN 5-HT(1A) activation suggests that the effects of
      the 5-HT(1A) treatments on the intake of NaCl are not due to mechanisms producing
      a nonspecific decrease of all ingestive behaviors.

PMID- 17218027
TI  - Role of c-fos gene in vasoactive intestinal peptide promoted synthesis of
      pulmonary surfactant phospholipids.
AB  - We previously reported that vasoactive intestinal peptide (VIP) promoted
      synthesis of phosphatidylcholine (PC) in alveolar type II (ATII) cells. But the
      intracellular mechanism for this effect was unknown. In this work, we
      investigated the intracellular signal transduction pathway for VIP promoted
      synthesis of PC, the major lipid component of pulmonary surfactant (PS), by using
      an antagonist of VIP receptors, inhibitor of protein kinase C (PKC) and antisense
      oligonucleotides (AS-ODN) for c-fos oncogene. Our results showed that: 1 in
      circle [D-P-Cl-Phe(6)-Leu(17)]-VIP (10(-6) mol/l), an antagonist of VIP
      receptors, could decrease the quantity of [(3)H] choline incorporation,
      microsomal choline-phosphate cytidylyltransferase (CCT) mRNA expression and CCT
      activity induced by VIP (10(-8) mol/l) in cultured lung explants to the control
      levels; 2 in circle VIP (10(-8) mol/l) upregulated c-Fos protein expression in
      ATII cells. AS-ODN for c-fos oncogene (9x10(-6) mol/l) could block the elevation
      of [(3)H] choline incorporation, microsomal CCT mRNA expression and CCT activity
      induced by VIP in cultured lung explants and in ATII cells; 3 in circle H7 (10(
      5) mol/l), a PKC inhibitor could also reduce VIP induced [(3)H] choline
      incorporation, microsomal CCT mRNA expression and CCT activity in cultured lung
      explants and in ATII cells. These results demonstrated that VIP receptors, PKC
      and c-Fos protein played important roles in the signaling pathway through which
      VIP promoted the synthesis of PC.

PMID- 17218028
TI  - The frequency of aspirin resistance and its risk factors in patients with
      metabolic syndrome.
AB  - BACKGROUND: Although different populations were examined for the incidence of
      aspirin resistance, the frequency and related risk factors for aspirin resistance
      in patients with metabolic syndrome have not been reported yet. This study aimed
      to determine the frequency of aspirin resistance and its risk factors in patients
      with metabolic syndrome. METHODS: We performed a cross-sectional study in 110
      patients with metabolic syndrome. After one week of 100 mg/day aspirin, blood
      samples were obtained. Platelet function analyzer (PFA-100) was used to determine
      the frequency of aspirin resistance. Endothelial functions, carotid intima media
      thickness, and the presence of plaques in the carotid arteries were evaluated for
      subclinical atherosclerosis and the levels of inflammatory markers were assessed
      as risk factors for aspirin resistance. The presence of subclinical
      atherosclerosis was defined as a maximum carotid intima media thickness of > or =
      0.9 mm and/or the presence of carotid atheroma. RESULTS: Aspirin resistance was
      detected in 21.9% of the patients. In the multivariate analysis, hs-CRP levels
      (odds ratio [95% CI]=2.8 [1.3-5.9], p=0.009), diastolic blood pressure, (0.9 [0.8
      1.0], p=0.007), and the presence of subclinical atherosclerosis (4.1 [1.4-12.2],
      p=0.012) were statistically significant risk factors for aspirin resistance.
      CONCLUSIONS: We concluded that the frequency of aspirin resistance confirmed in
      this cohort of patients with metabolic syndrome was higher in patients with a
      lower diastolic blood pressure, higher hs-CRP levels and atherosclerotic changes
      in their carotid arteries.

PMID- 17218029
TI  - A new device for rapid evaluation of biofilm formation potential by bacteria.
AB  - This work describes the implementation of a new assay named the BioFilm Ring Test
      to evaluate the ability of bacteria to form biofilms. This assay is based on the
      immobilisation (or not) of magnetic beads embedded by bacterial aggregates or
      mats (patented concept). It is realised on modified polystyrene 96-wells
      microtiter plates with individual 8-wells slides. The kinetic of biofilm
      formation of four bacterial species, Listeria monocytogenes, Escherichia coli,
      Staphylococcus carnosus and Staphylococcus xylosus was evaluated with this new
      device by comparison with the standard crystal violet staining method of sessile
      cells. In parallel, the biofilm growth was visualized by Scanning Electron
      Microscopy (SEM) observations. The BioFilm Ring Test gave similar but faster
      results than the crystal violet method. Moreover, the new assay was easier to
      implement, more reproducible and allowed high throughput screenings due to
      limited manipulations (no washing and staining steps) and rapid and accurate
      measurements of magnetic bead immobilisation by sessile bacterial cells.

PMID- 17218030
TI  - Regarding Davis et al.: Assessment of (18)F PET signals for automatic target
      volume definition in radiotherapy treatment planning.

PMID- 17218031
TI  - Limited survey for the occurrence of aflatoxins in cereals and poultry feeds from
      Rabat, Morocco.
AB  - Fifty eight (58) samples of cereals for human consumption (20 corn flour, 17
      wheat flour) and poultry feeds (n=21) purchased from popular markets of Rabat in
      Morocco were analyzed for aflatoxins (AF) by HPLC with immunoaffinity column
      (IAC) clean-up and fluorimetric detection. The incidence of AF in corn, wheat
      flour and poultry feeds was about 80, 17.6 and 66.6% respectively. High
      contamination levels were found in corn and poultry feeds samples. Levels of
      contamination of analyzed samples with AFB1 ranged from 0.23 to 11.2, 0.03 to
      0.15 and 0.05 to 5.38 ng/g for corn, wheat and poultry feeds respectively.
      Results showed also that the contamination of 10% of samples of corn was higher
      than the limit set by EU regulations for AFB1 and total AF. This is the first
      report on the determination of AF in corn, wheat and poultry feeds from Morocco
      by HPLC and IAC.

PMID- 17218032
TI  - Acid adaptation affects the viability of Salmonella typhimurium during the lactic
      fermentation of skim milk and product storage.
AB  - In this study, Salmonella typhimurium was acid adapted at pH 5.5 for 4 h. The
      viability of the acid-adapted and non-adapted cells of S. typhimurium was
      investigated both during the lactic fermentation of skim milk with Streptococcus
      thermophilus or Lactobacillus bulgaricus, and during the storage of lactic
      fermented milk products at 5 degrees C. It was found that the viable population
      of S. typhimurium, regardless of acid adaptation, increased in skim milk during
      the initial 24 h of lactic fermentation and then declined. However, the viable
      population of acid-adapted S. typhimurium was significantly higher (P<.05) than
      that of non-adapted cell at the end of 48 h of fermentation. Acid-adapted cells
      of S. typhimurium were also found to have survived better than non-adapted cells
      in the S. thermophilus-prepared fermented milk and two commercial lactic
      fermented milk products. The viability of the acid-adapted and non-adapted S.
      typhimurium at 5 and 37 degrees C in cell-free fermented milks that had their pHs
      adjusted to 6.4 and skim milk (pH 6.4) was further investigated. Results revealed
      that acid adaptation, in addition to enhancing acid tolerance, reduced the
      susceptibility of S. typhimurium to refrigerated temperature and other
      detrimental factors which might be present in lactic fermented milk products.
      These responses all contribute to the enhanced survival of acid-adapted S.
      typhimurium in the lactic fermented milk products observed in the present study.

PMID- 17218033
TI  - Overexpression of biologically active VEGF121 fusion proteins in Escherichia
      coli.
AB  - Vascular endothelial growth factor-A (VEGF) exists as five different isoforms,
      which exert their growth stimulatory effects through interaction with the FLK and
      KDR receptors. The VEGF(121) isoform has been employed as a highly selective
      carrier of therapeutic agents to target tumor endothelial cells resulting in
      inhibition of tumor growth and metastasis. VEGF(121) and VEGF(121)/rGel fusion
      toxin containing hexa-histidine tags were expressed in Escherichia coli AD494
      (DE3) pLysS. Media containing glycerol as a primary carbon source increased the
      specific expression levels of soluble VEGF(121) and VEGF(121)/rGel (mg/L/OD10) by
      more than two-fold over LB media when grown in a batchtype cultivation in a
      bioreactor. High cell densities over OD 40 were achieved using a fed-batch method
      and employing feeding medium containing glycerol and yeast extract. The overall
      production of the target proteins was improved 18-fold for VEGF(121) (59.2mg/L)
      and 27-fold for VEGF(121)/rGel (42.5mg/L), respectively, compared to the
      conventional flask cultivation method (3.3 and 1.6mg/L for VEGF(121) and
      VEGF(121)/rGel, respectively). The purified VEGF(121) and VEGF(121)/rGel fusion
      proteins were biologically active as assessed by phosphorylation of KDR receptors
      and cytotoxicity against KDR expressing cells.

PMID- 17218034
TI  - Characterization of a hydroxyl-radical-producing glycoprotein and its presumptive
      genes from the white-rot basidiomycete Phanerochaete chrysosporium.
AB  - During wood decay, the white-rot basidiomycete Phanerochaete chrysosporium
      secretes low-molecular-mass glycoproteins that catalyze a redox reaction between
      O(2) and electron donors to produce hydroxyl radical. This reaction accounts for
      most of the hydroxyl radical produced in wood-degrading cultures of P.
      chrysosporium. In combination with phenol oxidases, hydroxyl radical is believed
      to play a role in lignin degradation. The secreted glycoproteins also reduce
      Fe(III) to Fe(II) and strongly bind Fe(II). The partially purified glycoproteins
      contain 1-amino-1-deoxy-2-ketose (ketoamine) produced by the condensation of side
      chain amino groups and carbohydrate. cDNAs and two putative genes encoding these
      glycoproteins, glp1 and glp2, have been isolated and sequenced. The 875bp glp1
      and 864bp glp2 are found on scaffold 2 of the P. chrysosporium genome. These
      presumptive genes each consist of seven introns and eight exons. The latter
      encode a predicted protein of 138 amino acids and a 22-amino-acid signal sequence
      for secretion. The predicted protein sequences are nearly identical to N-terminal
      and internal sequences obtained from the partially purified glycoprotein. The
      molecular masses of the deduced mature proteins, 13,981 (glp1) and 13,970 (glp2),
      coincide with the molecular mass of the glycoprotein as determined by tricine-SDS
      PAGE.

PMID- 17218035
TI  - Characterization of M-class genome segments of muscovy duck reovirus S14.
AB  - This report documents the first sequence analysis of the entire M1, M2, and M3
      genome segments of the muscovy duck reovirus (DRV) S14. The complete sequence of
      each of the three M gene segments was determined. The M1 genome segment was 2283
      nucleotides in length and was predicted to encode muA protein of 732 residues.
      The Escherichia coli expressed M1 transcripts generated a 108kDa protein, as
      expected for muA. A cleavage product of muA, muA1, could be detected by Western
      blotting with duck anti-reovirus and mouse anti-muA polyclonal serum. muA was
      distributed diffusely in the cytoplasma and nucleus of transfected Vero cells,
      which provides evidence that muA might be functional related to the mammalian
      reovirus (MRV) mu2. The M2 gene was 2155 nucleotides in length and was predicted
      to encode muB major outer capsid protein of 676 amino acids. The M3 genome
      segment was 1996 nucleotides in length and was predicted to encode a muNS protein
      of 635 amino acids. It was unexpectedly found that 5'-termini of the M1 and M2
      genes ended with 5'-ACUUUU and 5'-UCUUUU, respectively, instead of 5'-GCUUUU,
      which is present on most mRNAs of other avian reoviruses (ARV). The UCAUC 3'
      terminal sequences of the S14 M1, M2, and M3 genome segments are shared by DRV,
      ARV, and MRV. Alignment of the DRV muA-, muB-, and muNS-encoding genes with ARV
      revealed 72.9-73.9%, 67.1-69.6%, and 69.4-70.8% nucleotide identity,
      respectively. The amino acid sequence homology between DRV and ARV ranged from
      85.3 to 86.2% (muA), 75.0 to 76.5% (muB), and 78.4 to 79.8% (muNS). Phylogenetic
      analyses of the M1, M2, M3, and S-class [Kuntz-Simon, G., Le Gall-Recule, G., de
      Boisseson, C., Jestin, V., 2002. Muscovy duck reovirus sigmaC protein is a
      typically encoded by the smallest genome segment. J. Gen. Virol. 83, 1189-1200;
      Zhang, Y., Liu, M., Hu, Q.L., Ouyang, S.D., Tong, G.Z., 2006a. Characterization
      of the sigmaC-encoding gene from muscovy duck reovirus. Virus Genes 36, 169-174;
      Zhang, Y., Liu, M., Ouyan, S.D., Hu, Q.L., Guo, D.C., Han, Z., 2006b. Detection
      and identification of avian, duck, and goose reoviruses by RT-PCR: goose and duck
      reoviruses aggregated the same specified genogroup in Orthoreovirus Genus II.
      Arch. Virol. 151, 1525-1538] genome segments suggests that DRV and ARV share a
      recent common ancestor and that the two lineages have subsequently undergone host
      dependent evolution.

PMID- 17218036
TI  - Silk microspheres for encapsulation and controlled release.
AB  - A method was developed to prepare silk fibroin microspheres using lipid vesicles
      as templates to efficiently load protein drugs in active form for controlled
      release. The lipid was subsequently removed by methanol or sodium chloride
      treatments, resulting in silk microspheres consisting of beta-sheet structure and
      about 2 mum in diameter. NaCl treated microspheres had smoother surfaces compared
      to the methanol treatments based on SEM analysis, and both types of microspheres
      had a mixture of multilamellar and unilamellar structures. A model protein drug,
      horseradish peroxidase, was encapsulated in the microspheres. Freeze-thaw cycles
      during preparation led to higher loading of the peroxidase due to improved mixing
      between the silk and drug, while without this process the drug and silk remained
      in separate layers or domains in microspheres. This partitioning was determined
      with fluorescein-labeled silk and rhodamine-labeled dextran. Small molecules such
      as the enzyme substrate 3,3',5,5'-tetramethylbenzidine, Mw=240 Da, and its
      oxidized product freely diffused through the MeOH- and NaCl-processed silk
      microspheres so that enzyme loading and activity could be determined. Enzyme
      activity was retained during processing and in the final microspheres. The enzyme
      release profile depended on the NaCl-process used in microsphere preparation. The
      physically cross-linked beta-sheet structure of silk fibroin and the residual
      lipids in the microspheres played important roles in controlling enzyme release
      profiles. The silk microspheres have the potential for diverse applications where
      controlled protein release from biocompatible, mechanically tough, and slowly
      biodegradable carriers is desirable.

PMID- 17218038
TI  - Assuring quality of drugs by monitoring impurities.
AB  - To assure the quality of drugs, impurities must be monitored carefully. It is
      important to understand what constitutes an impurity and to identify potential
      sources of such impurities. Selective analytical methods need to be developed to
      monitor them. It is generally desirable to profile impurities to provide a
      yardstick for comparative purposes. New impurities may be observed as changes are
      made in the synthesis, formulation, or production procedures, albeit for
      improving them. At times it is necessary to isolate and characterize an impurity
      when hyphenated methods do not yield the structure or when confirmation is
      necessary with an authentic material. Availability of an authentic material can
      also allow toxicological studies and provide a standard for routine monitoring of
      the drug product.

PMID- 17218037
TI  - High predictive value of early viral kinetics in retreatment with peginterferon
      and ribavirin of chronic hepatitis C patients non-responders to standard
      combination therapy.
AB  - BACKGROUND/AIMS: To evaluate the efficacy of peginterferon alfa-2b and ribavirin
      in unselected consecutive patients with chronic hepatitis C, treated outside of
      trials, who were relapsers or non-responders to interferon and ribavirin
      combination. METHODS: One hundred and fifty-four patients were evaluated. There
      were 101 non-responders and 53 relapsers to standard combination therapy.
      Patients were retreated with peginterferon alfa-2b 1.5 microg/kg/wk plus
      ribavirin 1000-1200 mg/day during 48 weeks. RESULTS: Forty-four patients (28.6%)
      achieved sustained virological response (SVR). Rapid (week 4) and early (week 12)
      virological response had high negative predictive values of SVR (94% and 97%,
      respectively); however positive predictive values were relatively low (52% and
      49%, respectively). Relapsers had higher SVR rates (58.5%) than non-responders
      (13%) p<0.0001. In non-responders, SVR raised to 50% in patients with genotype
      non-1 and mild or moderate fibrosis. In multivariate analysis, predictors of SVR
      were: relapse after interferon plus ribavirin combination, mild or moderate
      fibrosis, genotype non-1 and baseline viral load <2 million copies/ml.
      CONCLUSIONS: Relapsers to interferon plus ribavirin therapy, and non-responders
      with genotype non-1 and mild or moderate fibrosis, achieved a relatively high SVR
      rate following retreatment with peginterferon plus ribavirin. Early viral
      kinetics had a high negative predictive value of SVR.

PMID- 17218039
TI  - Microtubule dynamics in root hairs of Medicago truncatula.
AB  - The microtubular cytoskeleton plays an important role in the development of tip
      growing plant cells, but knowledge about its dynamics is incomplete. In this
      study, root hairs of the legume Medicago truncatula have been chosen for a
      detailed analysis of microtubular cytoskeleton dynamics using GFP-MBD and EB1-YFP
      as markers and 4D imaging. The microtubular cytoskeleton appears mainly to be
      composed of bundles which form tracks along which new microtubules polymerise.
      Polymerisation rates of microtubules are highest in the tip of growing root
      hairs. Treatment of root hairs with Nod factor and latrunculin B result in a
      twofold decrease in polymerisation rate. Nonetheless, no direct, physical
      interaction between the actin filament cytoskeleton and microtubules could be
      observed. A new picture of how the plant cytoskeleton is organised in apically
      growing root hairs emerges from these observations, revealing similarities with
      the organisation in other, non-plant, tip-growing cells.

PMID- 17218040
TI  - Optimisation of correlation weights of SMILES invariants for modelling oral quail
      toxicity.
AB  - The SMILES (simplified molecular input line entry system) nomenclature was used
      to elucidate the molecular structure in constructing the quantitative structure
      property/activity relationships (QSPR/QSAR) for predicting quail toxicity after
      oral exposure. The presence of chemical elements in different electronic states
      (e.g., C, c, O, o, Cl, Br, etc.) and of different covalent bonds (i.e., -,=, and
      #) was used as local invariants. Combinations of different presence/absence codes
      for local features of the SMILES were used as global invariants. The statistical
      characteristics of this model are n=97, r(2)=0.755, s=0.445, F=293 (training
      set); n=18, r(2)=0.731, s=0.587, F=43 (test set).

PMID- 17218041
TI  - An experimental in vivo analysis of the resorption to ultrasound activated pins
      (Sonic weld) and standard biodegradable screws (ResorbX) in sheep.
AB  - We compared the healing and reaction in the mandibles of 11 sheep of a
      conventional bioresorbable screw osteosynthesis with the newly developed
      ultrasound-activated pin osteosynthesis. The thermal stress caused by insertion
      of the ultrasound-aided pins leads to no cellular reaction around the pin. There
      is neither clinical nor histological evidence of any initial inflammation that
      could have been induced by the insertion. Adequate attachment of fibrous tissue
      to the pin head and the absence of any inflammation are important preconditions
      for the introduction of this new method of osteosynthesis into clinical practice.
      Further advantageous characteristics are easy intraoperative handling and a
      reduction in operating time, because cutting the thread is not required. There
      must be sufficient interlinkage of the polymer and the trabecular structures to
      ensure stability.

PMID- 17218042
TI  - Optimizing the molarity of a EDTA washing solution for saturated-soil remediation
      of trace metal contaminated soils.
AB  - Three experiments were conducted to optimize the use of
      ethylenediaminetetraacetic acid (EDTA) for reclaiming urban soils contaminated
      with trace metals. As compared to Na(2)EDTA, (NH(4))(2)EDTA extracted 60% more Zn
      and equivalent amounts of Cd, Cu and Pb from a sandy loam. When successively
      saturating and draining loamy sand columns during a washing cycle, which
      submerged it once with a (NH(4))(2)EDTA wash and four times with deionised water,
      the post-wash rinses largely contributed to the total cumulative extraction of
      Cd, Co, Cr, Cu, Mn, Ni, Pb and Zn. Both the washing solution and the deionised
      water rinses were added in a 2:5 liquid to soil (L:S) weight ratio. For equal
      amounts of EDTA, concentrating the washing solution and applying it and the
      ensuing rinses in a smaller 1:5 L:S weight ratio, instead of a 2:5 L:S weight
      ratio, increased the extraction of targeted Cr, Cu, Ni, Pb and Zn.

PMID- 17218043
TI  - Development of a new approach for microbial decontamination of water using
      modified Fenton's reaction.
AB  - Microbial decontamination of water was carried out using a novel radical
      generating system consisting of ion exchange resin, copper and hydrogen peroxide.
      The system was successful in reducing the microbial load in water by more than
      99% in 15 min and is effective against all the microorganisms tested. The method
      was also successful in decontaminating the flood water obtained from Industrial
      Canal and 17th Street Canal in New Orleans. Decontamination is due to the
      formation of hydroxyl radicals, formed during the decomposition of hydrogen
      peroxide by the metal-polymer complex.

PMID- 17218044
TI  - Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon
      derivatives to larval Rana boylii.
AB  - Organophosphorus pesticides (OPs) are ubiquitous in the environment and are
      highly toxic to amphibians. They deactivate cholinesterase, resulting in
      neurological dysfunction. Most chemicals in this group require oxidative
      desulfuration to achieve their greatest cholinesterase-inhibiting potencies. Oxon
      derivatives are formed within liver cells but also by bacterial decay of parental
      pesticides. This study examines the toxicity of chlorpyrifos, malathion and
      diazinon and their oxons on the foothill yellow-legged frog (Rana boylii). R.
      boylii is exposed to agricultural pesticides in the California Central Valley.
      Median lethal concentrations of the parental forms during a 96 h exposure were
      3.00 mg/L (24h) for chlorpyrifos, 2.14 mg/L for malathion and 7.49 mg/L for
      diazinon. Corresponding oxons were 10 to 100 times more toxic than their parental
      forms. We conclude that environmental concentrations of these pesticides can be
      harmful to R. boylii populations.

PMID- 17218045
TI  - New considerations regarding the risk assessment on Tartrazine An update
      toxicological assessment, intolerance reactions and maximum theoretical daily
      intake in France.
AB  - Tartrazine is an artificial azo dye commonly used in human food and
      pharmaceutical products. Since the last assessment carried out by the JECFA in
      1964, many new studies have been conducted, some of which have incriminated
      tartrazine in food intolerance reactions. The aims of this work are to update the
      hazard characterization and to revaluate the safety of tartrazine. Our
      bibliographical review of animal studies confirms the initial hazard assessment
      conducted by the JECFA, and accordingly the ADI established at 7.5mg/kg bw. From
      our data, in France, the estimated maximum theoretical intake of tartrazine in
      children is 37.2% of the ADI at the 97.5th percentile. It may therefore be
      concluded that from a toxicological point of view, tartrazine does not represent
      a risk for the consumer. It appears more difficult to show a clear relationship
      between ingestion of tartrazine and the development of intolerance reactions in
      patients. These reactions primarily occur in patients who also suffer from
      recurrent urticaria or asthma. The link between tartrazine consumption and these
      reactions is often overestimated, and the pathogenic mechanisms remain poorly
      understood. The prevalence of tartrazine intolerance is estimated to be less than
      0.12% in the general population. Generally, the population at risk is aware of
      the importance of food labelling, with the view of avoiding consumption of
      tartrazine. However, it has to be mentioned that products such as ice creams,
      desserts, cakes and fine bakery are often sold loose without any labelling.

PMID- 17218046
TI  - Factors affecting primary care physicians' perceptions of health system reform in
      Israel: professional autonomy versus organizational affiliation.
AB  - This paper examines primary care physicians' perceptions of a National Health
      Insurance Law that introduced managed competition into Israel's health care
      system, and the factors affecting their perceptions. Between April and July 1997,
      we conducted a mail survey of primary care physicians employed by Israel's four
      health plans (which are managed care organizations). Eight hundred questionnaires
      were returned, representing a response rate of 86%. The findings indicate that,
      overall most physicians support the components of the National Health Insurance
      Law with statistically significant differences among physicians by health plan.
      Multivariate analysis revealed that, contrary to theoretical expectations, a
      perceived decrease in professional autonomy and in the status of the profession
      following reform did not significantly affect attitudes toward national health
      insurance. These findings highlight the need for additional empirical studies to
      further examine theoretical contentions about the implications of infringing on
      the professional autonomy and the dominant status of physicians. The principal
      and most interesting finding of this study was the independent effect of health
      plan affiliation on physicians' attitudes toward each of the five components of
      the National Health Insurance Law, after controlling for background
      characteristics, for the reform's perceived effect on the physicians' autonomy
      and status in the health plan, and for the reform's perceived effect on the level
      of health plan services and the health plan's financial situation. We found that
      physicians' perceptions tended to conform to the formal position of their health
      plan, suggesting the need to analyze the attitudes of physicians in their
      organizational context, rather than treating them as members of a uniform
      professional community.

PMID- 17218047
TI  - Antidepressant-like effect of magnetic resonance imaging-based stimulation in
      mice.
AB  - INTRODUCTION: It has been reported that a novel type of magnetic resonance
      imaging (MRI) scan called echo planar magnetic resonance spectroscopic imaging
      (EP-MRSI) may show antidepressant effects. We examined whether the two routine
      diagnostic protocols of MRI [T1 and echo planar diffusion weighted imaging (EPI
      DWI)], have antidepressant-like effects in an animal model of depression.
      METHODS: The effects of standard EPI-DWI and T1 MRI on immobility, swimming and
      climbing times in the modified forced swimming test (FST) in mice were examined.
      After exposure to the first session of modified forced swimming test, we randomly
      divided the mice into four groups. The first group (T1 MRI group, n=21) received
      a 15-minute stimulation of T1 sequence. The second group (EPI-DWI MRI group,
      n=21) received a 15-minute stimulation of EPI-DWI protocol. The third group (sham
      group, n=21) spent 15 min in a tunnel similar to the MRI gantry in terms of size,
      temperature and light intensity and received recorded sounds from a normal
      session of EPI-DWI with similar duration and intensity. The fourth group acted as
      controls (n=21). The second session of the modified FST was conducted twelve
      hours later. The mean of immobility, swimming and climbing times in this session
      were compared to the control group. RESULTS: T1 weighted and EPI-DWI MRI groups
      showed a reduction in immobility time compared to the control group (P
      value<0.002, P value<0.017 respectively). This effect is comparable to that seen
      in the FST after the administration of antidepressant agents. The climbing time
      in the group subjected to EPI-DWI MRI was longer than the control group (P
      value<0.035). Previous studies showed similar effects after the administration of
      antidepressant drugs affecting the catecholamine systems. The swimming time in
      the T1 MRI group was significantly longer than the control group (P value<0.037).
      Previous studies showed qualitatively similar effect to that of anti-depressant
      drugs affecting the serotoninergic systems. The swimming, climbing and immobility
      times in the sham and control groups showed no significant difference.
      CONCLUSIONS: Our findings raise the possibility that MRI-based stimulation may
      have antidepressant-like effects in mice. This is likely to be through different
      mechanisms in T1 weighted and EPI-DWI protocols. However the possible biological
      basis of this effect is not yet understood and we would advocate further studies
      of MRI-based stimulation effects on transmitters in the different organs in the
      body specially the brain.

PMID- 17218048
TI  - Contribution of divergent thinking to community functioning in schizophrenia.
AB  - Fluency deficits have been associated with poor community functioning in patients
      with schizophrenia. In our previous study we demonstrated that the ability to
      generate higher-quality responses on tasks of divergent thinking as measured by
      several fluency tests was impaired in patients with schizophrenia. The purpose of
      the present study was to investigate the contribution of the deficits in
      divergent thinking to community dysfunction in schizophrenia. Forty Japanese
      outpatients with schizophrenia and 32 healthy control subjects were recruited for
      this study and assessed over a broad spectrum of the neurocognitive domain. Their
      capacity for divergent thinking was assessed by idea, design, and word fluency
      tests. Community functioning was assessed by using the Global Assessment of
      Functioning (GAF), the Life Assessment Scale for the Mentally Ill (LASMI), and
      the Social Functioning Scale (SFS). The results confirmed the qualitative
      deficits of divergent thinking in schizophrenia. Stepwise multiple regressions
      using neurocognitive and demographic/clinical variables as predictors revealed
      that the higher-quality response scores on the tasks of divergent thinking
      significantly contributed to community functioning. Moreover, the deficit on the
      verbal task of divergent thinking significantly contributed to impairment in the
      area of daily living, and the deficit on the nonverbal task of divergent thinking
      significantly contributed to impairment in the area of interpersonal relations.
      The results of this study reveal the importance and the possibility of cognitive
      remediation and cognitive training with strategies that target capacity for
      divergent thinking to improve community functioning in patients with
      schizophrenia.

PMID- 17218049
TI  - Acute dystonia resulting from abrupt bupropion discontinuation.
AB  - Acute dystonia is commonly associated with high-potency antipsychotics. Some
      cases of acute dystonia had been reported to be associated with antidepressant.
      However, only few reported cases are related to bupropion. As reported herein,
      the patient with major depression suffered from acute dystonia twice, which
      resulted from abrupt bupropion discontinuation. The first episode occurred when
      medicament was shifted from bupropion to duloxetine abruptly. The patient was
      requested with nothing per mouth (NPO) due to panendoscopic examination.
      Therefore, the second one emerged after the patient was suspended from two doses
      of bupropion. The symptoms of dysphagia, trismus and torticollis in these two
      episodes were resolved after bupropion reinstitution or biperiden injection. So
      far as we know by our documents, this is the first report concerning an acute
      dystonia resulting from bupropion discontinuation.

PMID- 17218050
TI  - Long-term effects of ochratoxin A on fibrosis and cell death in human proximal
      tubule or fibroblast cells in primary culture.
AB  - Ochratoxin A (OTA) is a mycotoxin produced by several fungi which grow on human
      food source material. Consumption of OTA is almost unavoidable. The consumption
      leads to low but detectable amounts of OTA in human blood. Risk assessment of OTA
      is based on studies performed either in animals or cultured cells. So far, mainly
      cell lines of different origin were used. To be as close as possible to the
      situation in humans with respect to the experimental setup, we studied the effect
      of OTA in human proximal tubule cells (RPTEC) and human fibroblasts in primary
      culture. OTA was administered at concentrations ranging from 0.3 nmol/l up to 10
      micromol/l for time periods up to 14 days. Apoptotic and necrotic cell death,
      collagen I, III, IV and fibronectin secretion as well as NF-kappaB activation
      were studied. Under our experimental conditions OTA exerted comparable effects on
      caspase-3 activity and necrosis in both cell types, however RPTEC were more
      sensitive (order of 10). Surprisingly, very low concentrations of OTA (0.3-10nM)
      led to cell hypertrophy during prolonged exposure (14 days). RPTEC but not
      fibroblasts responded with an increase of NF-kappaB activity and collagen III as
      well as fibronectin secretion underlining the profibrotic action of OTA in the
      kidney. Collagen I and IV secretion was only slightly changed. The results
      presented here give good reasons to re-asses the risk of OTA consumption leading
      to low blood concentrations which have so far been considered harmless.

PMID- 17218052
TI  - A comparative framework for understanding the biological principles of adult
      neurogenesis.
AB  - Adult neurogenesis has been identified in all vertebrate species examined thus
      far. However, an evolutionary trend towards a reduction in both the number of
      proliferation zones and the overall number of newborn cells has been revealed in
      more recent lineages of vertebrates, such as mammals. Adult neurogenesis, and in
      particular the characterization of adult neural stem cells in mammals has been
      the focus of intense research with the goal of developing new cell-based
      regenerative treatments for neurodegenerative diseases, spinal cord injury, and
      acute damage due to stroke. Conversely, most other vertebrate classes, which
      display widespread production of adult neurons, are not typically used as model
      systems in this context. A more profound understanding of the structural
      composition and the mechanisms that support proliferation zones in the mature
      brain have become critical for revealing how adult neural stem cells are
      maintained in these regions and how they regulate neurogenesis. In this review we
      argue that comprehensive analyses of adult neurogenesis in various vertebrate and
      invertebrate species will lead to a more complete understanding of the
      fundamental biology and evolution of adult neurogenesis and provide a better
      framework for testing hypotheses regarding the functional significance of this
      trait.

PMID- 17218051
TI  - Dopaminergic toxicity of the herbicide atrazine in rat striatal slices.
AB  - A possible link between Parkinson's disease and pesticide exposure has been
      suggested, and recently it was shown that the herbicide atrazine (ATR) modulates
      catecholamine metabolism in PC12 cells and affects basal ganglia function in
      vivo. Hence, the objectives of this study were to: (i) determine if ATR is
      capable of modulating dopamine (DA) metabolism in striatal tissue slices in vitro
      and (ii) explore possible mechanisms of its effects. Striatal tissues from adult
      male Sprague-Dawley rats were incubated with up to 500 microM ATR in a metabolic
      shaker bath at 37 degrees C and an atmosphere of 95% O(2) and 5% CO(2) for 4h. At
      the end of incubation, samples were collected for both tissue and media levels of
      DA and its metabolites (3,4-dihydroxyphenylacetic acid, DOPAC and homovanillic
      acid, HVA), which were determined by high-performance liquid chromatography with
      electrochemical detection (HPLC-ECD). To gain some mechanistic insight in to the
      way ATR affects DA metabolism, several pharmacological manipulations were
      performed. Striata exposed to ATR at concentrations of 100 microM and greater had
      a dose-dependent decrease of tissue levels of DA. At doses of ATR 50 microM and
      greater, the DOPAC+HVA/DA ratio was dose-dependently increased. Tyrosine
      hydroxylase (TH, the rate-limiting enzyme in DA synthesis) protein levels and
      activity were not affected by ATR treatment. However, high potassium-induced DA
      release into the medium was decreased, whereas the increase in media DA observed
      in the presence of the DA uptake inhibitor nomifensine was increased even further
      by ATR in a dose-dependent manner. All of these effects of ATR were observed at
      levels that were not toxic to the tissue, as LDH release into the medium (lactate
      dehydrogenase, an index of non-specific cytotoxicity) was not affected by ATR.
      Taken together, results from this study suggest that ATR decreases tissue DA
      levels not by affecting TH activity, but possibly by interfering with the
      vesicular storage and/or cellular uptake of DA.

PMID- 17218053
TI  - Defining agents' behaviors to simulate complex residential development using
      multicriteria evaluation.
AB  - Cellular automata (CA) have been increasingly used to simulate complex
      geographical phenomena. These models may have limitations on reflecting
      individuals' behaviors which should be considered in urban simulation. Agent
      based modeling can solve some of the problems in addressing individuals'
      influences in urban systems. However, there is a general lack of methodology on
      how to define agents' properties. This paper uses multicriteria evaluation
      techniques to determine some of the parameters for the agent-based model.
      Empirical data from GIS are used to define agent's properties. Sensitivity
      analysis is also carried out to assess the influences of parameters on simulation
      outcomes. This model has been applied to the simulation of the residential
      development in a fast growing city, Guangzhou, in south China.

PMID- 17218054
TI  - Turnover of StAR protein: roles for the proteasome and mitochondrial proteases.
AB  - Steroidogenic acute regulatory protein (StAR) is a mitochondrial protein
      essential for massive synthesis of steroid hormones in the adrenal and the
      gonads. Our studies suggest that once synthesized on free polyribosomes, StAR
      preprotein either associates with the outer mitochondrial membrane to mediate
      transfer of cholesterol substrate required for steroidgenesis, or it is degraded
      by the proteasome. Proteasome inhibitors can prevent the turnover of StAR
      preprotein and other matrix-targeted preproteins. Once imported, excessive
      accumulation of inactive StAR in the matrix is avoided by a rapid turnover.
      Unexpectedly, mitochondrial StAR turnover can be inhibited by two proteasome
      inhibitors, i.e., MG132 and clasto-lactacystin beta-lactone, but not epoxomicin.
      Use of those inhibitors and immuno-electron microscopy data enabled a clear
      distinction between two pools of intra-mitochondrial StAR, one degraded by matrix
      protease(s) shortly after import, while the rest of the protein undergoes a
      slower and inhibitor resistant degradation following translocation onto to the
      matrix face of the inner membranes.

PMID- 17218055
TI  - Livin/ML-IAP as a new target for cancer treatment.
AB  - Livin is a member of the inhibitors of apoptosis protein (IAP) gene family, which
      encodes negative regulatory proteins that prevent cell apoptosis. Livin is
      selectively expressed in the most common human neoplasms and appears to be
      involved in tumor cell resistance to chemotherapeutic agents. Several studies in
      vitro and in vivo have demonstrated that down-regulation of Livin expression
      increases the apoptotic rate, reduces tumor growth potential and sensitized tumor
      cells to chemotherapeutic drugs. This review will focus on the role of this
      protein during cancer development and progression and will demonstrate possible
      targets for cancer therapy.

PMID- 17218056
TI  - Biosorption of chromium and nickel by heavy metal resistant fungal and bacterial
      isolates.
AB  - Microorganisms play a significant role in bioremediation of heavy metal
      contaminated soil and wastewater. In this study, heavy metal resistant fungi and
      bacteria were isolated from the soil samples of an electroplating industry, and
      the bioaccumulations of Cr(VI) and Ni(II) by these isolates were characterized to
      evaluate their applicability for heavy metal removal from industrial wastewaters.
      The optimum pH and temperature conditions for both the growth and heavy metal
      removal were determined for each isolate. The optimal pH for fungal isolates was
      lower (5-5.2) than that for bacterial isolates (7). The observed effect(s) of pH
      was attributable mainly to organism-specific physiology because in all the tested
      cases the cellular growth positively correlated with heavy metal removal. Batch
      and tolerance experiments provided information for solid retention time (SRT)
      design and the lethal tolerance limits for the isolated microorganisms.
      Experimental results indicated that expanded SRTs (stationary phase) can be
      recommended while using the fungal and bacterial Cr-resistant isolates for
      removing chromium. In the case of Ni-resistant bacterial isolate, a non-expanded
      SRT was recommended for designing continuous-flow completely stirred (CFCS)
      bioreactor so that a mid-log phase of cellular growth can be kept during the
      bioaccumulation process. The tolerance data with a high range of heavy metal
      concentrations revealed the Cr-resistant isolates, especially the fungal one,
      could tolerate chromium toxicity at up to 10,000 mg L(-1) chromium. Result
      indicates the applicability of the isolated Micrococcus sp. and Aspergillus sp.
      for the removal of chromium and nickel from industrial wastewater.

PMID- 17218057
TI  - Does the presence of sensory hypersensitivity influence outcomes of physical
      rehabilitation for chronic whiplash?--A preliminary RCT.
AB  - Patients with chronic whiplash associated disorders present with varied sensory,
      motor and psychological features. In this first instance it was questioned
      whether a multimodal program of physical therapies was an appropriate management
      to be broadly prescribed for these patients when it was known that some would
      have sensory features suggestive of a notable pain syndrome. A randomised
      controlled trial was conducted with 71 participants with persistent neck pain
      following a motor vehicle crash to explore this question. Participants were
      randomly allocated to receive either a multimodal physiotherapy program (MPT) or
      a self-management program (SMP) (advice and exercise). In the randomisation
      process, participants were stratified according to the presence or not of
      widespread mechanical or cold hyperalgesia. The intervention period was 10 weeks
      and outcomes were assessed immediately following treatment. Even with the
      presence of sensory hypersensitivity in 72.5% of subjects, both groups reported
      some relief of neck pain and disability (Neck Disability Index) and it was
      superior in the group receiving multimodal physiotherapy (p=0.04). Post-hoc
      observations however suggested that relief was marginal in the subgroup with both
      widespread mechanical and cold hyperalgesia. Further research is required to test
      the validity of this sub-group observation and to test the effect of the
      intervention in the long term.

PMID- 17218058
TI  - Ligustrazine attenuates acute myocardium injury after thermal trauma.
AB  - This study was designed to investigate the effects of ligustrazine on burn
      induced myocardiac injury as well as TNF-alpha levels in severely burned rats.
      Sprague-Dawley rats were divided into four groups: (1) sham group, rats who
      underwent sham burn; (2) fluid-resuscitated sham group (FRsham), rats who
      underwent sham burn, and lactated Ringer's solution for resuscitation; (3)
      control group, rats given third-degree burns over 30% total body surface area
      (TBSA) and lactated Ringer's solution for resuscitation; (4) ligustrazine group,
      rats given burn and lactated Ringer's solution with ligustrazine inside for
      resuscitation. Myocardial injury was assessed at 6h after burn by detecting serum
      levels of creatine kinase MB fraction (CK-MB) and lactate dehydrogenase (LDH), as
      well as water content, histological score, and ultrastructure change of cardiac
      tissue. In addition, myocardium ATP content was analyzed. Enzyme-linked
      immunosorbent assay (ELISA) was used to examine cardiac tumor necrosis factor
      alpha (TNF-alpha) levels. The results showed that burn trauma resulted in the
      increasing serum LDH and CK-MB, elevated myocardial water content, aggravated
      myocardial histological and ultrastructural lesions, increased myocardium ATP,
      and serum TNF-alpha. Ligustrazine 10mg/kg iv markedly inhibited increases in
      serum CK-MB and LDH, reduced myocardial water content from 76.91+/-0.19% in
      control group to 75.40+/-0.57%, significantly decreased the histologic scores of
      myocardium, and mollified the ultrastructural damage in cardiac myocytes.
      Ligustrazine significantly attenuated elevations in serum TNF-alpha level and
      myocardial ATP quantity. Therefore, our results demonstrate that ligustrazine
      exhibits significant protective effects on burn-induced myocardial injury via
      inhibiting the release of TNF-alpha and improving utilization of ATP.

PMID- 17218059
TI  - Burns caused by accidental overdose of photochemotherapy (PUVA).
AB  - This study was aimed to alert the hazard of accidental adverse reactions of
      photochemotherapy (Psoralen-UVA or PUVA) that has been used in the treatment for
      some skin diseases and commercially for cosmetic tanning. Aside from the
      predictable side effects of PUVA such as erythema and itching, the accidental
      adverse reactions such as extensive burns could occasionally occur. Our
      observations indicated that six cases resulted from mistakes of medical
      personnel, and six other cases resulted from unsupervised mistakes of patients.
      The conditions that needed photochemotherapy were seven cases of vitiligo, three
      cases of psoriasis and two cases of tanning. The accidental overdose of UV
      radiation was about 3-10 times the empirically normal dose. Five of our patients
      were supposed to undergo topical PUVA, but they were irradiated at the dose of
      oral PUVA. One patient applied 8-methoxypsoralen (8-MOP) cream together with
      taking 5-methoxypsoralen (5-MOP) tablets for oral PUVA. Three other patients
      enjoyed sunbathing 1-3h shortly after finishing PUVA. A young couple chose 5-MOP
      to enhance tanning and sunbathed about 1h later. When another patient resumed
      PUVA in a 6-month cessation, he was exposed at a previous dose instead of a
      starting dose. Erythema and blisters of second degree burns developed in all our
      cases, 36-72h after PUVA, with 5-25% of body surface involved. Among the 12
      patients, 3 were admitted and 9 were treated on an outpatient basis. All patients
      recovered in 1-3 weeks with no skin graft or no significant sequelae except post
      inflammatory hyperpigmentation.

PMID- 17218061
TI  - Abnormal inspiratory depth in Phox2a haploinsufficient mice.
AB  - Mutations of genes encoding Phox2a or Phox2b transcription factors induce
      modifications of different brainstem neuronal networks. Such modifications are
      associated with defects in breathing behavior at birth. In particular, an
      abnormal breathing frequency is observed in Phox2a-/- mutant mice, resulting from
      abnormal development of the locus coeruleus (LC) nucleus. However, the role of
      Phox2a proteins in the establishment of respiratory neuronal pathways is unknown,
      largely because mutants die shortly after birth. In the present study, we
      examined the effects of a haploinsufficiency of the Phox2a gene. Phox2a
      heterozygotes survive and exhibit a significantly larger inspiratory volume both
      during normoxic breathing and in response to hypoxia and a delayed maturation of
      inspiratory duration compared to wild-type animals. This phenotype accompanied by
      an unaltered frequency is evident at birth and persists until at least postnatal
      day 10. Morphological analyses of Phox2a+/- animals revealed no anomaly in the LC
      region, but highlighted an increase in the number of cells expressing tyrosine
      hydroxylase enzyme, a marker of chemoafferent neurons, in the petrosal sensory
      ganglion. These data indicate that Phox2a plays a critical role in the ontogeny
      of the reflex control of inspiration.

PMID- 17218060
TI  - Unilateral 6-hydroxydopamine lesion of dopamine neurons and subchronic L-DOPA
      administration in the adult rat alters the expression of the vesicular GABA
      transporter in different subsets of striatal neurons and in the substantia nigra,
      pars reticulata.
AB  - The loss of dopamine neurons combined or not with the subsequent administration
      of L-DOPA in patients with Parkinson's disease or in experimental models of the
      disease results in altered GABAergic signaling throughout the basal ganglia,
      including the striatum and the substantia nigra, pars reticulata. However, the
      molecular mechanisms involved in altered GABA neurotransmission remain poorly
      understood. In order to be released from synaptic vesicles, newly synthesized
      GABA is transported from the cytosol into synaptic vesicles by a vesicular GABA
      transporter. The objective of this study was to examine the hypothesis that
      expression of the vesicular GABA transporter (vGAT) is altered in the unilateral
      6-hydroxydopamine model of Parkinson's disease. Our results provide evidence that
      a unilateral 6-hydroxydopamine lesion results in increased and decreased vGAT
      mRNA levels in striatopallidal and striatonigral neurons, respectively. These two
      subsets of neurons were identified by the co-expression or lack of co-expression
      of preproenkephalin, a marker of striatopallidal neurons, using double-labeling
      in situ hybridization histochemistry. Such changes occurred in the striatum
      ipsilateral to the 6-hydroxydopamine lesion and were paralleled by decreased vGAT
      protein levels in the substantia nigra, pars reticulate (SNr). On the other hand,
      the subchronic systemic administration of L-DOPA increased vGAT mRNA levels in
      preproenkephalin-negative neurons on the side ipsilateral and, to a lesser
      extent, the side contralateral to the 6-hydroxydopamine lesion. Systemic L-DOPA
      also increased vGAT protein levels in the ipsi- and contralateral SNr. As a
      whole, the results provide original evidence that vGAT expression is altered in
      the 6-hydroxydopamine model of Parkinson's disease. They also suggest that the
      behavioral effects induced by a subchronic administration of L-DOPA to 6
      hydroxydopamine-lesioned rats involve an increase in the vesicular release of
      GABA by striatonigral neurons.

PMID- 17218062
TI  - Genome instability and DNA damage accumulation in gene-targeted mice.
AB  - Six major pathways for DNA repair have been identified. These include (1) DNA
      repair by direct reversal, (2) base excision repair, (3) mismatch repair, (4)
      nucleotide excision repair, (5) homologous recombination, and (6) non-homologous
      end-joining. In addition, several other cellular processes influence the response
      to DNA damage. The generation of gene-targeted organisms is crucial for assessing
      the relative contribution of single DNA repair proteins and DNA repair pathways
      in maintaining genome stability. In particular, the accumulation of DNA damage,
      mutations and cancer in unexposed gene-targeted animals illuminates the
      spontaneous load of a particular lesion and the relative significance of a single
      gene in a specific pathway. Strategies for the generation of gene-targeted mice
      have been available for 15 years and more than 100 different genes relevant to
      DNA repair have been targeted. This review describes some important progress made
      toward understanding spontaneous DNA damage and its repair, exemplified through
      one, or a few, gene-targeted mice from each major DNA repair pathway.

PMID- 17218063
TI  - Anti-allodynic efficacy of botulinum neurotoxin A in a model of neuropathic pain.
AB  - Neuropathic pain is typified by injuries to the peripheral and central nervous
      system and derives from such causes as cancer, diabetes, multiple sclerosis, post
      herpetic neuralgia, physical trauma or surgery, and many others. Patients
      suffering neuropathic pain do not respond to conventional treatment with non
      steroidal anti-inflammatory drugs and show a reduced sensitivity to opiates often
      associated with serious side effects. Recently, it has been demonstrated that
      botulinum neurotoxin serotype-A (BoNT/A) is able to induce analgesia in
      inflammatory pain conditions. The goal of this research was to test if BoNT/A was
      able to relieve also neuropathic pain symptoms. By using chronic constriction
      injury of the sciatic nerve, a mouse model of neuropathic pain, we observed that
      peripheral administration of BoNT/A strongly reduced the mechanical allodynia
      associated with this neuropathy. Remarkably, a single non-toxic dose of BoNT/A
      was sufficient to induce anti-allodynic effects, which lasted for at least 3
      weeks. This result is particularly relevant since neuropathic pain is poorly
      treated by current drug therapies. This communication enlarges our knowledge on
      potentially new medical uses of BoNT/A in efforts to ameliorate human health
      conditions, with very important implications in the development of new
      pharmacotherapeutic approaches against neuropathic pain.

PMID- 17218064
TI  - Is lactate food for neurons? Comparison of monocarboxylate transporter subtypes
      in brain and muscle.
AB  - Intercellular monocarboxylate transport is important, particularly in tissues
      with high energy demands, such as brain and muscle. In skeletal muscle, it is
      well established that glycolytic fast twitch muscle fibers produce lactate, which
      is transported out of the cell through the monocarboxylate transporter (MCT) 4.
      Lactate is then taken up and oxidized by the oxidative slow twitch muscle fibers,
      which express MCT1. In the brain it is still questioned whether lactate produced
      in astrocytes is taken up and oxidized by neurons upon activation. Several
      studies have reported that astrocytes express MCT4, whereas neurons express MCT2.
      By comparing the localizations of MCTs in oxidative and glycolytic compartments I
      here give support to the idea that there is a lactate shuttle in the brain
      similar to that in muscle. This conclusion is based on studies in rodents using
      high resolution immunocytochemical methods at the light and electron
      microscopical levels.

PMID- 17218065
TI  - alpha7 Nicotinic receptor gene delivery into mouse hippocampal neurons leads to
      functional receptor expression, improved spatial memory-related performance, and
      tau hyperphosphorylation.
AB  - Brain alpha7 nicotinic receptors have become therapeutic targets for Alzheimer's
      disease (AD) based on their memory-enhancing and neuroprotective actions. This
      study investigated the feasibility of increasing neuronal alpha7 receptor
      functions using a gene delivery approach based on neuron-selective recombinant
      adeno-associated virus (rAAV)-derived vectors. In order to determine whether
      alpha7 receptor-mediated cytotoxicity was dependent on receptor density, rat
      alpha7 nicotinic receptors were expressed at high concentrations in GH4C1 cells
      as measured with nicotine-displaceable [3H]methyllycaconitine (MLA) binding. The
      potency of GTS-21 (an alpha7 receptor agonist) to induce cell loss was similar in
      these cells to that seen in pheochromocytoma (PC12) cells expressing nine-times
      lower receptor levels, suggesting that cytotoxicity was more dependent on agonist
      concentration than receptor density. Hippocampal transduction with rat alpha7
      nicotinic receptors increased [3H]MLA binding in this region in wild type and
      alpha7 receptor-knockout (KO) mice without apparent cytotoxicity. No difference
      was observed in Kd values for MLA binding between endogenous and transgenic
      receptors. Single cell recordings demonstrated that dentate granule cells that
      normally have no alpha7 receptor response did so following alpha7 receptor gene
      delivery in wild type mice. Recovery of alpha7 function was also observed in
      stratum oriens and stratum radiatum neurons of KO mice following gene delivery.
      Wild type mice exhibited improved acquisition performance in the Morris water
      task 1 month after bilateral hippocampal transductions with the rat alpha7
      receptor gene compared with green fluorescent protein-transduced controls.
      However, both groups reached similar training levels and there was no difference
      in subsequent probe performance. Finally, this gene delivery approach was used to
      test whether alpha7 receptors affect tau-phosphorylation. Chronic (i.e. 2 month
      but not 2 week) expression of high levels of alpha7 receptors in hippocampus
      increased AT8 staining characteristic of hyperphosphorylated tau in that region,
      indicating that endogenous agonist-mediated receptor activation may be able to
      modulate this process.

PMID- 17218066
TI  - Patterns of drug use and expectations in methadone patients.
AB  - Expectations about future behavior have been shown to have a positive
      relationship with subsequent behavior. For patients in drug treatment, recovery
      should manifest changes in drug use and in cognitive perceptions of being able to
      refrain from use. The present study identified latent patterns of the
      longitudinal relationship between drug use expectation and illegal drug use
      during treatment. Latent variable mixture modeling identified three patterns of
      change over successive 3-month intervals during treatment: Improvers (48%),
      Decliners (33%), and Continuing Users (19%). The sample consisted of 497 patients
      in community-based outpatient methadone treatment. The utility of the latent
      patterns was shown through their relationship to treatment engagement, where
      Continuing Users had lower counseling rapport and time in treatment. These latent
      patterns also differed on drug use measures at follow-up. Additional analyses of
      expectations with measures of opioid use, cocaine use, or criminality yielded
      similar latent patterns. Expectations about future drug use were found to be a
      useful measure of cognitive change corresponding to drug use change. Its
      potential as a brief treatment management tool is noted.

PMID- 17218067
TI  - Incomplete tumor volume reduction may improve cancer prognosis.
AB  - Currently, chemotherapy, immunotherapy, and radiotherapy are the standard
      treatment for un-resectable solid malignant tumors. New "virtual scalpel"
      methods, such as MRI guided focused ultrasound, can target tumor tissues for
      destruction without the need for a resection and its possible complications.
      Unfortunately, the current state of the art cannot guarantee the safe and full
      destruction of all the targeted tissues. The main hypothesis is that for cancer
      patients, even incomplete tumor volume reduction will increase the efficiency of
      some systemic therapies as well as of natural healing mechanisms, and thus, may
      improve the quality of life and the prognosis. It is conjectured that partial
      tumor volume destruction will reduce the releases of endocrine substances from
      tumor cells, thus, improving the overall systemic condition. Furthermore, it may
      improve the efficiency of chemotherapy and immunotherapy and possibly trigger a
      natural immune response. The decrease of tumor volume may also slow down the
      process of invasion and metastasis. It is recommended that as a standard practice
      of palliative care, any un-resectable tumor volume will be considered for
      destruction with virtual scalpel techniques such as MRI guided focused
      ultrasound. Furthermore, it is suggested that this process is synergetic with
      chemotherapy and immunotherapy.

PMID- 17218068
TI  - Apolipoprotein M likely extends its anti-atherogenesis via anti-inflammation.
AB  - Apolipoprotein M (apoM), a novel human apolipoprotein recently discovered,
      predominantly presents in high density lipoprotein (HDL) in plasma, exclusively
      expressed in liver and in kidney. The present data demonstrated apoM protects
      against atherosclerosis (AS) primarily via partaking in prebeta-HDL formation and
      promoting cholesterol efflux to HDL. However, this lipid-metabolism-associated
      pathway seems unlikely responsible for all atheroprotective effects of apoM.
      Notably, the human apoM gene is just located in the major histocompatibility
      complex class III region (MHC-III) on chromosome 6, many genes in this region are
      related to the immune and inflammatory response. Furthermore, apoM has been
      documented to link with some inflammatory factors including platelet activating
      factor (PAF) and leptin. These evidences indicate that apoM may be involved in
      inflammatory activities in vivo and the potential immuno- and inflam-reactive
      property of apoM may contribute to the anti-inflammatory function of HDL, as
      generally acknowledged as an important atheroprotective mechanism of HDL.

PMID- 17218069
TI  - Characterization of the sigmaB-encoding genes of muscovy duck reovirus: sigmaC
      sigmaB-ELISA for antibodies against duck reovirus in ducks.
AB  - The sigmaB/sigmaC-encoding genes of muscovy duck reovirus (DRV) S12 strain were
      cloned, sequenced, and expressed in Escherichia coli. The sigmaC-encoding gene of
      DRV showed only 21-22% identity to that of avian reovirus (ARV) at both
      nucleotide and amino acid level. The sigmaB-encoding gene of DRV comprised 1163bp
      with one open reading frame (ORF). The ORF comprised 1104bp and encoded 367 amino
      acids with a predicted molecular mass of 40.44 kDa. A zinc-binding motif and a
      basic amino acid motif were found within the predicted amino acid sequence of
      sigmaB. The identities between the S12 and ARV were 59.3-64.0% and 60.9-62.5%,
      respectively, at the nucleotide and deduced amino acid levels. Phylogenetic
      analysis of the sigmaB-encoding gene sequence indicated that S12 separated as a
      distinct virus relative to other avian strains. The expressed sigmaB/sigmaC
      fusion proteins in E. coli could be detected, approximately 45 and 50kDa,
      respectively, by duck anti-reovirus polyclonal serum. In addition, an ELISA
      (sigmaB-sigmaC-ELISA) using the expressed sigmaB-sigmaC proteins as coating
      antigen for detection of antibodies to DRV in ducks was developed. In comparison
      with the virus neutralization test and agar gel immuno-diffusion test (AGID), the
      sigmaB-sigmaC-ELISA showed perfect specificity and sensitivity. The sigmaB-sigmaC
      ELISA did not react with the antisera to other duck pathogens, implying that
      these two proteins were specific in recognition of DRV antibodies. Taken
      together, the results demonstrated that sigmaB-sigmaC-ELISA was a sensitive and
      accurate method for detecting antibodies to DRV.

PMID- 17218070
TI  - Quantification of mucosa-adhered microbiota of lambs and calves by the use of
      culture methods and fluorescent in situ hybridization coupled with flow cytometry
      techniques.
AB  - The intestinal mucosa-associated microbiota could play important biological roles
      due to its close proximity with the animal host, but knowledge on its composition
      is still limited. The aim of this study was to characterize the microbial
      communities tightly associated with different parts (rumen, duodenum and colon)
      of the gastrointestinal tract (GIT) of healthy lambs and calves by using both
      cultural, and fluorescent in situ hybridization-flow cytometry (FCM-FISH)
      techniques. Lactic acid bacteria genera were one of the predominant bacteria
      detected in lambs and calves by both methodologies, possibly constituting an
      index of their healthy status. The levels of Lactobacillus were significantly
      higher (p<0.05) in the rumen and duodenum of lambs, and in the rumen of calves.
      The levels of Bifidobacterium were significantly higher (p<0.05) in the colon of
      both animal species and the rumen of lambs. Significant differences (p<0.05) were
      found in counts of other microbial groups (yeast, Enterococcus,
      Propionibacterium, Bacteroides, Clostridium and Enterobacteriaceae) at diverse GI
      sections depending on the animal species. In general, microbial counts follow the
      same trends regardless the applied technique. The most remarkable differences
      were found in detection levels of Bacteroides and Clostridium, which tended to be
      significantly higher (p<0.05) when analysed by FCM-FISH. This technique also
      allowed the detection of quantitatively important bacteria (sulphate-reducing
      bacteria, Atopobium and Coriobacterium), which are difficult to cultivate in
      selective medium. Therefore, FCM-FISH has been proven to be a sensitive high
      throughput approach that provides additional information to that obtained by
      traditional culture techniques about the complexity of the GI ecosystem of these
      animal species.

PMID- 17218072
TI  - Investigation of triboelectric charging in dry powder inhalers using electrical
      low pressure impactor (ELPI).
AB  - Electrostatics and triboelectrification phenomena in dry powder inhalers (DPI)
      are not well understood, but as shown in this study they may play an important
      role. Using model formulations of albuterol in lactose, the extent of
      triboelectrification in the operation of DPI was investigated using an electrical
      low pressure impactor (ELPI). An experimental apparatus was developed, the
      performance of the ELPI was evaluated for consistency and reproducibility, and
      compared to a conventional inertial impactor. Using a statistical experimental
      design the effects of lactose type, drug load, capsule fill, capsule material,
      and inhaler were assessed. DPI formulations appear to be subject to strong
      triboelectric effects. Charge separation can occur between different size
      fractions, i.e. different fractions can carry charges of different sign. In
      particular, lactose type, inhaler, and capsule material have a strong effect on
      the magnitude and polarity of the charge developed during DPI operation. The
      study suggests that the polarity of the aerosol can be controlled by choice of
      lactose type, capsule material, and inhaler, which could be exploited for
      targeting different lung physiologies.

PMID- 17218071
TI  - DNA damage caused by benzo(a)pyrene in MCF-7 cells is increased by verapamil,
      probenecid and PSC833.
AB  - The aim of this study was to clarify whether pharmaceutical drugs capable of
      inhibiting ABC-transporters affect the toxicity of benzo(a)pyrene (BP). MCF-7
      breast adenocarcinoma cells were cultured for 24 and 48 h with benzo(a)pyrene (1
      microM) and the transporter inhibitors verapamil (0.125-100 microM), PSC833 (0.05
      5 microM) or probenecid (0.05-2 mM). DNA binding of benzo(a)pyrene-7,8-diol-9,10
      epoxide (BPDE) was analyzed by synchronous fluorescence spectrophotometry and p53
      protein by immunoblotting. BP metabolism was studied using thin layer
      chromatography (TLC). MTT assay and ATP quantitation were used for the analysis
      of cell viability. At 24 h there was no statistically significant increase in the
      DNA-adduct formation by any of the used inhibitors. However, at 48 h all of the
      inhibitors, in concentrations known to effectively block ABC transporters,
      increased the BPDE-DNA adduct formation 1.5 to 2-fold compared to adduct
      formation with BP only. PSC833 and verapamil also increased p53 protein
      expression at 48 h (p<0.05). Probenecid decreased glucuronidation of (3)H-BP
      metabolites. Other inhibitors did not decrease statistically significantly the
      overall formation of water-soluble metabolites. BP alone slightly decreased
      viability of cells at 48 h according to ATP quantitation as compared to vehicle
      treated controls (86.4+/-16.4%). Even though the used inhibitors showed some
      cytotoxicity, the combination of BP and inhibitors did not decrease cell
      viability in synergistic manner. According to these results certain
      pharmaceutical drugs may increase DNA damage caused by benzo(a)pyrene in MCF-7
      cells at least partly through the inhibition of transporters. Taking into account
      the complex metabolism of BP and lack of specificity of the inhibitors used, it
      is likely that increased DNA damage seen in this study was the result of multiple
      interactions between the inhibitors, BP metabolism and the efflux of the
      compounds.

PMID- 17218073
TI  - Aging and T-cell diversity.
AB  - Naive and memory CD4 and CD8 T cells constitute a highly dynamic system with
      constant homeostatic and antigen-driven proliferation, influx, and loss of T
      cells. Thymic activity dwindles with age and essentially ceases in the later
      decades of life, severely constraining the generation of new T cells. Homeostatic
      control mechanisms are very effective at maintaining a large and diverse subset
      of naive CD4 T cells through the 7th decade of life, but eventually and abruptly
      fail at about the age of 75 years. In contrast, the CD8 T cell compartment is
      more unstable, with progressive diminution of naive T cells and increasing loss
      of diversity during mid adulthood. Vaccination strategies need to aim at
      developing a broad repertoire of memory T cells before the critical time period
      when the naive CD4 T-cell repertoire collapses. Research efforts need to aim at
      understanding T-cell homeostatic control mechanisms to ultimately expand the time
      period of repertoire stability.

PMID- 17218074
TI  - Targeting difficult accessible breast lesions: MRI-guided needle localization
      using a freehand technique in a 3.0 T closed bore magnet.
AB  - PURPOSE: To report the accuracy of magnetic resonance imaging (MRI)-guided needle
      localization for diagnosis of MRI detected suspicious breast lesions located in
      difficult accessible regions of the breast, using the freehand method in a 3.0 T
      closed bore magnet. MATERIALS AND METHODS: In five patients with five MRI-only
      breast lesions underwent MRI-guided needle localization for histopathologic
      evaluation of the lesions. All interventional procedures were performed in a 3.0
      T MRI system with the patient in prone position and by using a dedicated phased
      array breast coil. MRI-guided needle localizations were performed by using a
      freehand technique. In our study, the high-resolution scan allowed preprocedural
      localization of all lesions without use of contrast enhancement. In all cases
      contrast-enhanced MRI was performed after insertion of the wire to confirm the
      tip of the wire in direct contact with the enhancing lesion. RESULTS: Needle
      localizations were performed in five patients. Histopathologic evaluation of
      tissue after surgery excision biopsy revealed one lymph node, three invasive
      ductal carcinoma and one ductal carcinoma in situ. Lesion size varied from 6 to
      30 mm. Mean duration time was 25 min. No complications occurred during the
      intervention method. In the patient with the benign lesion control MRI of the
      breast after 6 months confirmed lesion removal. CONCLUSIONS: MRI-guided needle
      localization by using a freehand technique in a 3.0 T closed bore magnet is a
      safe and accurate method for diagnosis of difficult accessible breast lesions
      only visible on MRI.

PMID- 17218075
TI  - Widening the spectrum of PRES: series from a tertiary care center.
AB  - Posterior reversible encephalopathy syndrome (PRES) has been defined as a
      neurologic disorder with distinct radiologic findings demonstrating lesions in
      the subcortical white matter at posterior circulation territory. Several authors
      suggested alternative descriptive terms for this syndrome as atypical radiologic
      features have been described more frequently. In this retrospective study, we
      sought to determine the frequency and features of radiologic findings in the
      setting of a tertiary care center. We also noticed that some of our patients had
      simultaneous multiple conditions that were previously shown to cause PRES
      independently in the literature. These probable predisposing factors were also
      revisited.

PMID- 17218076
TI  - Can lymphoscintigraphy and gamma probe method in sentinel node biopsy for
      differentiated thyroid carcinoma obviate the disadvantages of the blue-dye
      method?

PMID- 17218077
TI  - WITHDRAWN: Adjuvant portal vein chemotherapy improves the efficacy of hepatectomy
      for hepatocellular carcinoma with portal vein tumor thrombus.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17218078
TI  - Significance of serum hepatocyte growth factor levels in patients with
      hepatocellular carcinoma undergoing hepatic resection.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen and may
      stimulate the proliferation and invasiveness of human hepatocellular carcinoma
      (HCC) cells through the c-met receptor. This study evaluates the significance of
      serum HGF levels in patients undergoing HCC resection. STUDY DESIGN: The
      peripheral and portal sera and HCC and non-tumorous tissues of 40 HCC patients,
      with tumor TNM stage I (n=12), II (n=17), and III (n=11) diseases, who underwent
      hepatic resection were prospectively collected. Serum HGF levels were determined
      by enzyme-linked immunosorbent assay. The c-met protein expressions were examined
      by immunohistochemistry. Median follow-up time was 69 months. RESULTS: The
      prehepatectomy portal HGF levels (median, 622pg/mL) were significantly higher
      than peripheral HGF levels (564pg/mL) (P=0.026). The posthepatectomy portal HGF
      levels (699pg/mL) were significantly higher than prehepatectomy portal HGF levels
      (P<0.001). C-met expression was detected in 87.5% HCC and in 85.0% non-tumorous
      liver tissues. By Cox multivariate analysis, posthepatectomy portal HGF level
      >699pg/mL (P<0.001), multiple tumors (P=0.042), and TNM stages II (P=0.019) and
      III (P=0.009) were independent factors related with survival. Patients with a
      posthepatectomy portal HCG level >699pg/mL and with a positive c-met expression
      in HCC tissue have the worst survival. CONCLUSIONS: In HCC patients, high
      peripheral and portal HGF serum levels related with poor prognosis after hepatic
      resection. Hepatocyte growth factor and c-met receptor can be targets of future
      HCC postoperative treatment.

PMID- 17218079
TI  - Initiating mechanisms of food allergy: Oral tolerance versus allergic
      sensitization.
AB  - Immediately after birth the mucosa of the gastrointestinal tract, which
      represents the greatest body surface area exposed to the outside environment, is
      confronted with a large variety of foreign antigens. The immune system of the
      intestine now has to meet the task of discriminating between pathogens and
      harmless antigens, such as food proteins and commensal bacteria, and to respond
      accordingly. This important job is fulfilled by cells of the gut-associated
      lymphoid tissue, the largest immunologic organ in the body. Despite the large
      extent of food antigen exposure, only a small percentage of individuals
      experience adverse immunologic reactions to food. This is due to the fact that
      the normal immune response to dietary proteins is associated with the induction
      of oral tolerance, which refers to a state of active inhibition of immune
      responses to an antigen by means of prior exposure to that antigen via the oral
      route. Abrogation of oral tolerance or failure to induce oral tolerance may
      result in the development of food hypersensitivity. In the present review,
      factors that may play a role in the outcome of oral tolerance versus
      sensitization to food proteins are discussed.

PMID- 17218080
TI  - Effects of various pesticides on human 5alpha-reductase activity in prostate and
      LNCaP cells.
AB  - Certain pesticides are able to disturb the sex steroid hormone system and to act
      as antiandrogens. While the different underlying mechanisms remain unclear,
      inhibition of 5alpha-reductase, the enzyme which is indispensable for the
      synthesis of DHT and thus normal masculinization, appears to be one of the
      sensitive targets for endocrine disruption. We therefore tested several endocrine
      disrupters with antiandrogenic effects in vivo for their influence on 5alpha
      reductase activity in two different test systems: (a) an enzyme assay with human
      Lymph Node Carcinoma of Prostate (LNCaP) cells and (b) an enzyme assay with human
      prostate tissue homogenate. The selected pesticides and industrial compounds were
      monobutyltin (MBT), dibutyltin (DBT), tributyltin (TBT), triphenyltin (TPT),
      diuron, fenarimol, linuron, p,p'DDE, prochloraz and vinclozolin. The synthetic
      androgen methyltestosterone and the synthetic antiandrogen flutamide, as well as
      the 5alpha-reductase inhibitor finasteride served as control compounds. The
      effect of the organotin compounds DBT, TBT and TPT on enzyme activity was
      approximately the same in both test systems, with IC(50) values ranging between
      2.7 and 11.2 microM, while in prostate tissue, methyltestosterone and prochloraz
      proved to be stronger inhibitors (IC(50) values of 1.9 and 12.4 microM) than in
      LNCaP cells (IC(50) values of 13.2 and 53.2 microM). The inhibitory impact of
      finasteride was approximately 130 times stronger in prostate tissue than in LNCaP
      cells. Fenarimol, flutamide, linuron and p,p'DDE inhibited 5alpha-reductase
      activity only at very high concentrations (IC(50)> or =24 microM) in prostate
      homogenates, and not at all in LNCaP cells. On average, the IC(20) values were
      3.5 times lower than the IC(50) values. Diuron, MBT and vinclozolin exerted no
      effect in either of the test systems. The finding of pesticides acting as 5alpha
      reductase inhibitors might be of clinical relevance. As a screening tool for
      putative ED, the tissue assay is the more practical and sensitive method.
      However, the cell assay can, to some extent, reflect particular cell processes
      since the living cell is able to compensate moderate toxicological effects of the
      ED on cell viability, and possibly also their impact on 5alpha-reductase
      activity.

PMID- 17218081
TI  - Fine-mapping and comprehensive transcript analysis reveals nonsynonymous variants
      within a novel 1.17 Mb blood pressure QTL region on rat chromosome 10.
AB  - The presence of blood pressure (BP) quantitative trait loci (QTL) on rat
      chromosome 10 has been clearly demonstrated by linkage analysis and substitution
      mapping. Using congenic strains containing the LEW rat chromosomal segments on
      the Dahl salt-sensitive (S) rat background, further iterations of congenic
      substrains were constructed and characterized to fine-map a chromosome 10 region
      (QTL1) linked to blood pressure. Comparison of seven congenic substrains refined
      QTL1 to a 1.17 Mb segment flanked by D10Mco88 and D10Mco89, which are located at
      71,513,116 and 72,684,774 bp, respectively. The newly defined QTL1, containing 18
      genes, is captured in its entirety within a single congenic substrain. A thorough
      transcript analysis revealed that 3 of these 18 genes, Ccl5, Ddx52, and
      RGD1559577, had nonsynonymous allelic variations between the S rat and the LEW
      rat. None of the detected transcripts within the newly defined QTL1 are
      implicated directly in BP control in humans or model organisms. Therefore, the
      present work defines a novel blood pressure QTL with three potential quantitative
      trait nucleotides.

PMID- 17218082
TI  - Methimazole embryopathy: a contribution to defining the phenotype.
AB  - It has been suggested that children prenatally exposed to methimazole may present
      some features in common but the phenotype remains to be defined. The reported
      facial features include upward slanted palpebral fissures, arched flared eyebrows
      and small nose with a broad bridge. Choanal atresia and other anomalies like
      esophageal atresia and aplasia cutis were also described with this embryopathy.
      Additionally, developmental delay was reported in some patients along with one of
      these major malformation. We present a patient with the mentioned facial
      features, developmental delay and radio-ulnar synostosis whose mother has been
      exposed to methimazole during pregnancy and any other ethiological cause could be
      recognize.

PMID- 17218083
TI  - Biologically active anti-nerve growth factor antibodies in commercial intravenous
      gammaglobulin.
AB  - Neurotrophins are regulators of development, survival and function of neuronal
      and non-neuronal cells, one of the most important of which is nerve growth factor
      (NGF). Previous studies have demonstrated the presence of antibodies to NGF in
      normal human serum. It would therefore be predicted that antibodies to NGF would
      also be present in commercial intravenous gammaglobulin (IVIg). It has been shown
      in the present investigation that ELISA can detect anti-NGF antibodies in IVIg.
      The functional activity of these antibodies has been demonstrated after affinity
      purification, by their inhibitory effects upon (a) the proliferation of the NGF
      responsive rat pheochromocytoma cell line PC-12, (b) the differentiation of PC-12
      cells as determined by neurite outgrowth. All batches of commercially tested IVIg
      contained anti-NGF antibodies. Since NGF has an important role in the
      inflammatory immune response and in cell growth and differentiation, these
      findings may (a) facilitate our understanding of the mechanisms of action of
      IVIg, (b) indicate new disease states in which IVIg or its derivatives may exert
      beneficial effects.

PMID- 17218084
TI  - Effects of alcohol consumption and antipsychotic medication on brain morphology
      in schizophrenia.
AB  - Magnetic resonance imaging (MRI) studies have shown smaller volumes of grey
      matter (GM) and white matter (WM) both in schizophrenia and among patients with
      alcohol abuse or dependence. The effect of alcohol consumption in non-clinical
      alcohol consumers, i.e. subjects not recruited as having alcohol use disorders is
      less studied. In the present study, we investigated the effects of alcohol
      consumption, antipsychotic medication and a diagnosis of schizophrenia on
      variation in brain volumes among patients recruited for having schizophrenia and
      a group of age and gender matched control subjects. A total of 69 patients with
      schizophrenia (n=56), schizoaffective disorder (n=12) and schizophreniform
      disorder (n=1) and 97 control subjects were included. Alcohol Use Disorder
      Identification Test (AUDIT) was used to estimate alcohol consumption. In the
      entire group of patients and controls higher AUDIT score was significantly
      related to smaller volumes of WM. When ten patients and six control subjects who
      met lifetime diagnostic criteria for alcohol use disorders were excluded only a
      trend level association between AUDIT score and WM volumes was found. Having a
      diagnosis of schizophrenia was related to smaller volumes of total, frontal and
      temporal WM, total and temporal GM, and larger volumes of total, frontal and
      temporal cerebrospinal fluid (CSF). A diagnosis of schizophrenia remained a
      significant factor for smaller WM volumes even when the effect of alcohol
      consumption was taken into account. Antipsychotic medication was related to
      larger volumes of temporal CSF. This study demonstrates that alcohol consumption
      is an important factor for variation in WM volumes, and this effect should be
      taken into account in all studies evaluating brain volumes from MR images.

PMID- 17218085
TI  - Change of purple membranes geometry induced by protein adsorption.
AB  - Earlier it was an orthodoxy that purple membranes (PMs) in aqueous medium are
      shaped as flat hard disks. In a few newer articles it has been shown that PMs are
      bent and their curvature varies with surface charge density. The purpose of this
      work is to answer which is the dominant factor for PM bending--structural or
      electrostatic forces. Two positively charged proteins are used:
      phytohemagglutinin (PhHA) and protamine. The electrophoretic mobility and
      electric polarizability of PMs are measured by microelectrophoresis and electric
      dichroism. The results show that both proteins reduce the mobility because they
      are adsorbed on PM surface. However, their influence on the electric
      polarizability is in the opposite direction--protamine reduces it (trivial
      effect) while PhHA increases the polarizability (non-trivial effect). The last
      result is explained by a straightening the initially bent PM because of specific
      bonding of PhHA to asymmetrically disposed glycolipids of PM in contrast to the
      electrostatic adsorption of protamine. It has been concluded that PMs in water
      medium are bent in the same manner as in in vivo--the intracellular surface with
      a higher negative charge is concave. The results indicate that electrostatic
      forces play a significant role in PM curvature but the shape of structural
      elements is the main factor determining the geometry of PM.

PMID- 17218086
TI  - Coupling of lactose molecules to the carrier protein hinders the spleen and bone
      marrow uptake of doxorubicin conjugated with human albumin.
AB  - Several attempts have been made to enhance doxorubicin (DOXO) concentrations in
      tumour cells by drug conjugation with human albumin (HSA). HSA-DOXO has the
      drawback of causing DOXO accumulation in spleen and bone marrow, with a
      consequent leucopoenia not produced when lactose molecules are coupled to the
      carrier protein. In the present experiments we demonstrated that the effect of
      HSA lactosamination is not a consequence of a more rapid disappearance from the
      bloodstream of the lactosaminated conjugate (L-HSA-DOXO), which is rapidly
      internalized by the liver through the asialoglycoprotein receptor, but is due to
      a hindered uptake by spleen and bone marrow cells caused by the coupled lactose
      molecules. Experiments in vitro showed that HSA-DOXO produced an inhibition of
      murine macrophage proliferation not caused by L-HSA-DOXO. This result can be
      explained by higher amounts of the former conjugate entering in these cells and
      suggests macrophages as the cell type responsible for the spleen and bone marrow
      internalization of HSA-DOXO hindered by lactose coupling. Importantly,
      lactosamination of HSA did not reduce the marked uptake of HSA-DOXO by chemically
      induced rat hepatocellular carcinoma. L-HSA-DOXO, by avoiding DOXO accumulation
      in bone marrow is an attractive candidate for clinical trials against tumors
      which were found to actively internalize this conjugate in laboratory animals,
      such as hepatocellular carcinoma.

PMID- 17218087
TI  - Population modelling to describe pharmacokinetics of amiodarone in rats:
      relevance of plasma protein and tissue depot binding.
AB  - The objective of this paper was to characterize the disposition phase of AM in
      rats, after different high doses and modalities of i.v. administration. Three
      fitting programs, WINNONLIN, ADAPT II and NONMEM were employed. The two-stage
      fitting methods led to different results, none of which can adequately explain
      amiodarone's behaviour, although a great amount of data per subject is available.
      The non-linear mixed effect modelling approach allows satisfactory estimation of
      population pharmacokinetic parameters, and their respective variability. The best
      model to define the AM pharmacokinetic profile is a two-compartment model, with
      saturable and dynamic plasma protein binding and linear tissular depot dynamic
      binding. These results indicate that peripheral tissues act as depots, causing an
      important fall in AM plasma levels in the first moment after dosing. Later, the
      return of the drug from these depots causes a slow increase in serum
      concentration whenever the dose is reduced.

PMID- 17218088
TI  - [End of life and clinical research in pediatric oncology].
AB  - The objective of a phase I trials in paediatrics is to determine the recommended
      dose of a new treatment in children while evaluating its toxicity. These trials
      are proposed when no effective curative treatment is available. The probability
      of a benefit in terms of disease control is certainly very low, but greater than
      zero. On the basis of the work conducted by an Assistance publique-Hopitaux de
      Paris Espace ethique group in collaboration with parents, healthcare personnels
      and a philosopher, phase I therapeutic trials can be considered to be an
      ethically acceptable proposal provided the criteria and risks of inclusion in
      such a trial are clearly defined. This article discusses the main elements of
      this process and is designed to provide guidelines for healthcare personnel and
      parents. The need for an information provided gently but honestly, the importance
      of a sufficient time to think about the proposed trial, a two-sided dialogue and
      partnership between the various actors, and the priority given to the child's
      best interest, as should always be the case, constitute the decisive elements to
      guide the proposed inclusion in a phase I trial. These conditions help to ensure
      that a decision is reached which appears to be morally founded for all parties,
      while allowing the child to remain alive up until the end, i.e. a human being
      capable of relating. This decision allows parents and healthcare personnel to
      retain a good self-image; if the child dies, it is by keeping their self-esteem
      that parents can live with their bereavement and healthcare personnel can
      reinvest in other patients.

PMID- 17218089
TI  - Mass spectroscopic characterisation of oligomeric proanthocyanidins derived from
      an extract of Pelargonium sidoides roots (EPs 7630) and pharmacological screening
      in CNS models.
AB  - Chromatographic fractionation of proanthocyanidin oligomers from an aqueous
      ethanolic extract of Pelargonium sidoides roots (EPs 7630) gave a diverse set of
      epigallo- and gallocatechin based oligomers, which are connected by A and B-type
      bonds. Additionally, two series of monosubstituted oligomers were detected by
      mass spectroscopy, sulphates and aminoconjugates. In vivo studies investigating
      motility, body weight gain, body temperature, motoric coordination,
      anticonvulsant effects and central analgesic activities, showed no or only
      moderate pharmacological effects, indicating, that they have no intrinsic
      behavioural activities.

PMID- 17218090
TI  - Layer-by-layer self-assembly aluminum Keggin ions/Prussian blue nanoparticles
      ultrathin films towards multifunctional sensing applications.
AB  - In this study we described the nanocomposites films of specially synthesized
      inorganic Prussian blue (PB) nanoparticles and polyoxocation Al(13) Keggin ions
      that possess the excellent sensing activities. Film fabrication using layer-by
      layer (LBL) self-assembly technique was followed by electrochemical
      characterization. The assembled multilayer Al(13)/PB films as sensor devices for
      both the catalytic reduction of H(2)O(2) and detecting the change of relative
      humidity were also investigated. The sensitivity of the biosensor was 0.886 mA
      cm(-2)mM(-1), and about two orders of magnitude change in resistance was observed
      as the relative humidity increasing from 5 to 95%. Both sensors exhibited good
      reproducibility, wide linear range. The performance and multifunctional abilities
      of these nanocomposites promise potential applications in biosensors,
      environmental controlling system and biomedical devices.

PMID- 17218091
TI  - Nanopore sensor for fast label-free detection of short double-stranded DNAs.
AB  - Functionalizing surface enhanced the molecular sensing ability of a fabricated
      nanopore by increasing the translocation duration time for a short double
      stranded DNA. The surface of nanopore was derivatized with gamma
      aminopropyltriethoxysilane and the positively charged surface attracted DNA
      molecules when they were in the vicinity of nanopore. The translocation duration
      time of DNA increased due to the strong electrostatic interaction and it enabled
      us to detect a short double-stranded DNA (<1 kbp) that is under the size limit of
      a conventional solid state nanopore sensor. Both 539 and 910 bp double-stranded
      DNAs were analyzed with the surface functionalized nanopore and their
      translocation kinetics are presented in this work. The new feature of the surface
      modified nanopore that can detect short double-stranded DNA molecules could
      readily be applied for a rapid label-free diagnostic analysis in a Lab-On-a-Chip
      type DNA sensor.

PMID- 17218092
TI  - Adaptability of the Vitamin D nuclear receptor to the synthetic ligand Gemini:
      remodelling the LBP with one side chain rotation.
AB  - The crystal structure of the ligand binding domain (LBD) of the wild-type Vitamin
      D receptor (VDR) of zebrafish bound to Gemini, a synthetic agonist ligand with
      two identical side chains branching at carbon 20 reveals a ligand-dependent
      structural rearrangement of the ligand binding pocket (LBP). The rotation of a
      Leu side chain opens the access to a channel that can accommodate the second side
      chain of the ligand. The 25% increase of the LBP's volume does not alter the
      essential agonist features of VDR. The possibility to adapt the LBP to novel
      ligands with different chemistry and/or structure opens new perspectives in the
      design of more specifically targeted ligands.

PMID- 17218093
TI  - Difluoromethyl analogs of the natural hormone 1alpha,25-dihydroxyvitamin D3:
      Design, synthesis, and preliminary biological evaluation.
AB  - Three new Vitamin D analogs 3-5 incorporating a -CHF(2) group as an -OH surrogate
      have been prepared. Two of these new analogs (3 and 5) are strongly
      antiproliferative toward murine keratinocytes and are approximately 50 times less
      calciuric in vivo than the natural hormone calcitriol. The transcriptional
      activity of the 25-CHF(2) analog 3 is higher than that of the 1-CHF(2) analog 4.

PMID- 17218094
TI  - Vitamin D intakes in North America and Asia-Pacific countries are not sufficient
      to prevent vitamin D insufficiency.
AB  - Worldwide, vitamin D status is suboptimal relative to circulating levels of 25
      hydroxyvitamin D (25OHD) needed to prevent a variety of chronic conditions,
      however, it has long been assumed that dietary intake is sufficient to meet needs
      when sun exposure is limited. In the USA, mean vitamin D intake from foods is
      close to 5 microg, the Dietary Reference Intake (DRI) recommendation for persons
      up to 50 years; however, the amount of vitamin D needed to maintain a sufficient
      25OHD level during winter is >12.5 microg, and that needed for darkly pigmented,
      veiled, or sun protected persons is >50 microg. In the USA, most vitamin D intake
      from foods is provided by fortification. Canada and New Zealand have fewer
      fortified choices, and intakes are correspondingly lower. Supplement use can
      increase mean intake to >12.5 microg but does not always reach those who need it
      most. Serum 25OHD levels in New Zealand reveal much more insufficiency than
      expected, especially for Pacific people and Maori; low serum 25OHD concentrations
      are seen throughout the Asia-Pacific region. Fortification and supplementation
      may be effective to achieve intakes of 12.5 microg vitamin D in some of the
      population, but for many achieving the amount needed in the absence of skin
      synthesis requires intakes above the current upper level for vitamin D of 50
      microg.

PMID- 17218095
TI  - The 1alpha,25-dihydroxy Vitamin D3 receptor preferentially recruits the
      coactivator SRC-1 during up-regulation of the osteocalcin gene.
AB  - Binding of 1alpha,25-dihydroxy Vitamin D3 to the C-terminal domain (LBD) of its
      receptor (VDR), induces a conformational change that enables interaction of VDR
      with transcriptional coactivators such as the members of the p160/SRC family or
      the DRIP (Vitamin D interacting complex)/Mediator complex. These interactions are
      critical for VDR-mediated transcriptional enhancement of target genes. Recent
      reports indicate that nuclear receptors, including VDR, interact with p160/SRC
      members and the DRIP/Mediator complex in a sequential, cyclical, and mutually
      exclusive manner when bound to a target promoter, exhibiting also a high exchange
      rate. Here, we present an overview of how these coactivators are recruited to the
      bone-specific osteocalcin (OC) gene in response to short and long exposures to
      1alpha,25-dihydroxy Vitamin D3. We find that in intact osteoblastic cells VDR and
      SRC-1 rapidly bind to the OC promoter in response to the ligand. This recruitment
      correlates with transcriptional enhancement of the OC gene and with increased
      histone acetylation at the OC promoter. In contrast, binding of the DRIP205
      subunit, which anchors the DRIP/Mediator complex to the VDR, is detected at the
      OC promoter after several hours of incubation with 1alpha,25-dihydroxy Vitamin
      D3. Together, our results indicate that VDR preferentially recruits SRC-1 to
      enhance basal bone-specific OC gene transcription. We propose a model where
      specific protein-DNA and protein-protein interactions that occur within the
      context of the OC gene promoter in osteoblastic cells stabilize the preferential
      association of the VDR-SRC-1 complex.

PMID- 17218096
TI  - Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to
      define adequate nutritional vitamin D status.
AB  - Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by
      which we define nutritional vitamin D status. There is much debate, however, with
      respect to what a healthy minimum level of circulation 25(OH)D should be. Recent
      data using various biomarkers such as intact parathyroid hormone (PTH),
      intestinal calcium absorption, and skeletal density measurements suggest this
      minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between
      circulating vitamin D(3) and its metabolic product-25(OH)D(3) has not been
      studied. We investigated this relationship in two separate populations: the
      first, individuals from Hawaii who received significant sun exposure; the second,
      subjects from a lactation study who received up to 6400IU vitamin D(3)/day for 6
      months. Results (1) the relationship between circulating vitamin D(3) and 25(OH)D
      in both groups was not linear, but appeared saturable and controlled; (2) optimal
      nutritional vitamin D status appeared to occur when molar ratios of circulating
      vitamin D(3) and 25(OH)D exceeded 0.3; at this point, the V(max) of the 25
      hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D
      exceeded 100 nmol. We hypothesize that as humans live today, the 25-hydroxylase
      operates well below its V(max) because of chronic substrate deficiency, namely
      vitamin D(3). When humans are sun (or dietary) replete, the vitamin D endocrine
      system will function in a fashion as do these other steroid synthetic pathways,
      not limited by substrate. Thus, the relationship between circulating vitamin D
      and 25(OH)D may represent what "normal" vitamin D status should be.

PMID- 17218097
TI  - Enhancers located in the vitamin D receptor gene mediate transcriptional
      autoregulation by 1,25-dihydroxyvitamin D3.
AB  - The regulatory actions of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on target
      genes are mediated by the vitamin D receptor (VDR). Interestingly, one of the
      genomic targets of 1,25(OH)(2)D(3) action is the VDR gene itself; however, the
      mechanism underlying this regulation is unknown. We investigated VDR
      autoregulation by screening the mouse VDR locus from 20kb upstream of the
      transcriptional start site (TSS) to 10kb downstream of the last exon using
      chromatin immunoprecipitation (ChIP)-DNA microarray analysis (ChIP/chip). Three
      potential VDR binding sites were located within introns lying downstream of the
      TSS and their activities confirmed through direct ChIP analysis. Further
      exploration revealed that one of these intronic regions was capable of conferring
      1,25(OH)(2)D(3) response to both a downstream heterologous promoter and the
      minimal VDR promoter. Importantly, this regulatory region contained a classic
      vitamin D response element and was highly conserved within the human gene. We
      also demonstrated using ChIP analysis that the binding of VDR is associated with
      co-localization of RXR and the enhanced entry of RNA polymerase II. Thus, each of
      these sites appears likely to contribute to VDR autoregulation. Our studies using
      ChIP/chip analysis coupled to more traditional approaches define a direct
      mechanism whereby the VDR gene is upregulated by 1,25(OH)(2)D(3).

PMID- 17218098
TI  - The development of CD-ring modified analogs of 1alpha,25-dihydroxyvitamin D.
AB  - During a 20-year collaboration the laboratories of UGent and KU Leuven have
      developed different series of Vitamin D analogs characterized by structural
      modifications in the central CD-ring system. Modifications have first involved
      the introduction of substituents at C11 and the epimerization at C14, and
      subsequently more drastic changes consisting in both ring deletion and
      enlargement relative to the natural CD-ring system. Lately, the focus has shifted
      towards the synthesis of analogs featuring a symmetrical CD-ring core. As an
      illustration two different series are presented.

PMID- 17218099
TI  - Chiral tetrahydroquinoline derivatives as potent anti-hyperalgesic agents in
      animal models of sustained inflammation and chronic neuropathic pain.
AB  - Chiral tetrahydroquinoline derivatives have been prepared by an asymmetric
      Mannich-type condensation reaction using commercially available
      vinyloxyethylsilane and a N-arylimino R-(+)-t-butyl lactate ester, in the
      presence of a catalytic amount of metal triflates as Lewis acids. This synthetic
      approach gave rise to the target aldehyde intermediate in moderate facial
      diastereoselectivity and in high chemical yield. This efficient route enabled to
      scale up the synthesis of an orally bioavailable glycine antagonist showing
      outstanding in vivo anti-hyperalgesic activity in different animal models of
      sustained inflammation and chronic neuropathic pain.

PMID- 17218100
TI  - Achieving tight glycaemic control.
AB  - The implementation of tight glycaemic control (TGC) is becoming accepted best
      practice within intensive care units throughout the world. It is recommended by
      the Surviving Sepsis Campaign and is included in the sepsis care bundle. The
      major impact of TGC is currently thought to be associated with reduced morbidity
      and mortality. The process of achieving TGC is, however, not without risk. In
      particular, the need for frequent, accurate blood glucose measurement and the
      possibility of prolonged, unrecognised hypoglycaemia are of concern. There is
      also the potential for patients who exhibit significant insulin resistance to
      require the administration of large amounts of insulin. The transfer of patients
      from the intensive care unit to the operating theatre or for computerised
      tomography during intensive insulin therapy is also hazardous. The purpose of
      this paper is to describe a series of nurse led pilot studies which aimed to
      introduce the process of TGC whilst maintaining patient safety. The results
      demonstrate the effectiveness of a staged approach and the achievement of TGC.

PMID- 17218101
TI  - Effect of an evidence-based paediatric fever education program on emergency
      nurses' knowledge.
AB  - INTRODUCTION: This study examined the effect of an educational intervention of
      factual knowledge on emergency nurses' knowledge and clinical decisions related
      to paediatric fever. METHOD: A prospective pre-test/post-test design was used.
      Emergency nurses' factual knowledge was measured by parallel multiple choice
      questions and the intervention for the study was an educational intervention
      consisting of two tutorials. Pre-test data were collected in early June 2005 and
      post-test data were collected during August 2005. RESULTS: Thirty-one emergency
      nurses completed the pre and post-test multiple choice questions. Emergency
      nurses' knowledge increased following the tutorials. Pre-test score was
      positively correlated with knowledge acquisition. Self-reports of independent
      decisions related to fever management were influenced by experience, hours of
      employment, level of appointment, postgraduate qualifications and pre-test score.
      DISCUSSION: High levels of variability in knowledge and knowledge acquisition
      suggest a review of undergraduate and postgraduate curricula is warranted.
      Although this study identified associations between independent fever management
      decisions and participant characteristics, further research is pivotal to better
      understanding these relationships.

PMID- 17218102
TI  - Guideline implementation fails to improve thrombolytic administration.
AB  - BACKGROUND: International randomised controlled trials conducted over the last
      two decades have consistently demonstrated improved mortality and morbidity
      resulting from thrombolytic therapy for patients with acute myocardial infarction
      (AMI). Subsequently, evidence-based guidelines have been designed and implemented
      to optimize thrombolytic delivery. The effect of evidence-based clinical
      guidelines on clinical practice is heavily influenced by strategies used to
      develop, disseminate and implement those guidelines. AIMS: This study evaluated
      the impact of a collaborative, multifaceted implementation strategy for AMI
      management guidelines on thrombolytic usage in the Loddon Mallee Region,
      Victoria, Australia. INTERVENTION: The multi-faceted implementation strategy
      included an inter-disciplinary team representing all treating venues contributing
      to the content of the "Guidelines for the Early Management of Acute Myocardial
      Infarction" followed by education sessions that coincided with the dissemination
      of the guidelines. METHODS: A retrospective medical records audit 12 weeks before
      and 12 weeks after the intervention was used to evaluate the impact on proportion
      of those patients eligible and receiving a thrombolytic and door-to-needle time.
      Variables of treating venue, age, gender, type of AMI, and type of transport to
      hospital were also measured to determine their impact on results. RESULTS AND
      CONCLUSIONS: A retrospective audit of 170 medical records found that the
      intervention appeared to have had no impact on the proportion of patients
      eligible and receiving a thrombolytic (74.2% vs. 62.5%: p=0.275), and door-to
      needle time (67.7 min vs. 60.5 min: p=0.759). Venue specific influences produced
      a variety of patterns in thrombolytic delivery that require further exploration.
      This suggests that a single solution approach across multiple venues will have
      limited impact.

PMID- 17218103
TI  - Modulating effects of a novel skin-lightening agent, alpha-lipoic acid
      derivative, on melanin production by the formation of DOPA conjugate products.
AB  - Sodium zinc dihydrolipoylhistidinate (DHLHZn) is a compound of
      Zn(2+)/dihydrolipoic acid derivate complex, which was developed for
      cosmetic/medical use. To characterize DHLHZn as a novel skin-lightening agent,
      inhibitory actions of DHLHZn on tyrosinase (including its reaction pathway) have
      been elucidated in this study. In a B16 melanoma cell system, DHLHZn was active
      in suppressing the synthesis of melanins as well as alpha-arbutin, well known as
      a depigmenting drug. Furthermore, in a tyrosinase assay, DHLHZn showed stronger
      inhibitory effect on DOPAchrome formation than other tyrosinase inhibitors such
      as kojic acid. Our previous report demonstrated that the sulfhydryl groups of
      lipoyl motif react with DOPAquinone to form lipoyl DOPA conjugates. We therefore
      postulated that conjugated products between DHLHZn and DOPAquinone might be
      formed. Upon reaction of DHLHZn with L-DOPA following tyrosinase-catalyzed
      oxidation, the formation of DHLH DOPA conjugated products was confirmed by HPLC
      tandem mass spectrometry using reserpine as the internal standard. In addition,
      the inhibitory kinetics analyzed by a Lineweaver-Burk plot exhibited the
      reversibility of DHLHZn as a competitive inhibitor with a KI value of 0.35
      microM. These results indicate that this covalent reaction might contribute to
      alternating DOPAquinone, which is a tyrosinase reaction product, and result in
      the competitive inhibitory effect of DHLHZn on DOPAchrome formation. DHLHZn may
      thus serve as a potentially effective skin-lightening agent, an effectiveness
      that is based on the compound's covalent scavenging of DOPAquinone resulting in
      depigmentation.

PMID- 17218104
TI  - Benzoic acid and pyridine derivatives as inhibitors of Trypanosoma cruzi trans
      sialidase.
AB  - Benzoic acid and pyridine derivatives inhibit recombinant trans-sialidase from
      Trypanosoma cruzi with I50 values between 0.4 and 1mM. The best compounds, 4
      acetylamino-3-hydroxymethylbenzoic acid and 5-acetylamino-6-aminopyridine-2
      carboxylic acid, provide new leads to inhibitors not containing the synthetically
      complex sialic acid structure. The weak inhibition by such compounds contrasts
      with their much stronger inhibition of neuraminidase from Influenza virus.

PMID- 17218105
TI  - Studies on acyclic pyrimidines as inhibitors of mycobacteria.
AB  - In vitro anti-mycobacterial activities of several 5-substituted acyclic
      pyrimidine nucleosides containing 1-(2-hydroxyethoxy)methyl and 1-[(2-hydroxy-1
      (hydroxymethyl) ethoxy)methyl] acyclic moieties are investigated against three
      mycobacteria viz. Mycobacterium tuberculosis, Mycobacterium bovis, and
      Mycobacterium avium, which cause serious infections and mortality in healthy
      people as well as patients with AIDS. 1-(2-Hydroxyethoxy)methyl-5-(1-azido-2
      haloethyl or 1-azidovinyl) analogs (4-7), 1-[(2-hydroxy-1
      (hydroxymethyl)ethoxy)methyl]-5-decynyluracil (37), and 1-[(2-hydroxy-1
      (hydroxymethyl)ethoxy)methyl]-5-dodecynyluracil (38) exhibited significant in
      vitro anti-tubercular activity against these mycobacteria.

PMID- 17218106
TI  - Separation of iron and cobalt using 59Fe and 60Co by dialysis of
      polyvinylpyrrolidone-metal complexes: a greener approach.
AB  - An environmentally benign method to separate iron and cobalt has been developed
      using a safe chemical, polyvinylpyrrolidone (PVP). The method involves dialysis
      of PVP-Fe and PVP-Co complexes against triple-distilled water. (59)Fe and (60)Co
      were used as radioactive tracers of iron and cobalt throughout the experiment. No
      other chemicals are required for clean separation of cobalt from iron. The
      optimum condition for separation has been obtained at pH 5 using 10% aqueous
      solution of PVP. The method is applicable from trace scale to macro-scale. Very
      high separation factors have been obtained.

PMID- 17218107
TI  - Posterior transposition of anterior leaflet for complete chordal preservation.
AB  - A method of complete chordal preservation based on posterior transposition of
      anterior leaflet is presented. The anterior leaflet and chordae are completely
      detached from the annulus and reimplanted as a large patch under the posterior
      leaflet. The excess tissue without chordae is excised and the remnant with all
      the chordae is plicated by sutures used to implant the prosthesis. The posterior
      leaflet is left intact. The technique is safe and reproducible and no
      complications related with the procedure have been observed at mid-term follow
      up. These results have led to a wider application of total chordal preservation
      during mitral valve replacement.

PMID- 17218109
TI  - Volumetric evaluation of the lung expansion following resection: a stereological
      study.
AB  - OBJECTIVE: Following lung resection, the thoracic cavity may be filled partially
      or completely by the remaining pulmonary tissue. To our knowledge, no study has
      yet evaluated this volumetric change in thoracic content using high resolution
      computed tomography (HRCT) scans. We aimed to evaluate the volume changes of the
      lungs using HRCT scans during the preoperative and postoperative periods.
      METHODS: In this study, we took HRCT scans of 25 patients preoperatively and 3
      months after the resection. All patients were male and their mean age was 59.6
      (40-75) years. The volume and volume fraction of individual pulmonary lobes were
      estimated by superimposing point-counting grids on the preoperative and
      postoperative HRCT scans. RESULTS: The means of total lung volume in all patients
      were 6.40+/-1.40l and 4.92+/-1.21l in the preoperative and postoperative periods,
      respectively. While 30.79+/-10.64% of pulmonary tissue was resected in expanded
      patients, the pulmonary tissue was diminished volumetrically by 18.51+/-15.96%
      postoperatively. Volumetric analyses showed that the remaining structures
      increased its volume by 12.28%. Thereby, almost 50% of the resected pulmonary
      tissue was recovered volumetrically by the remaining tissues. CONCLUSIONS:
      Present results showed that the volume and volume fraction of the total lung and
      individual lobes could be estimated practically on HRCT scan using the method
      proposed in this study. The obtained data not only provided information about
      actual postoperative progress but also information for predicting the possible
      postoperative course in patients prior to the resection.

PMID- 17218108
TI  - Topical use of antifibrinolytic agents reduces postoperative bleeding: a double
      blind, prospective, randomized study.
AB  - OBJECTIVE: Postoperative bleeding is still one of the most common complications
      of cardiac surgery. Antifibrinolytic agents successfully reduce bleeding, but
      there are controversies concerning adverse effects after their systemic use. By
      topical application of antifibrinolytic agents in pericardial cavity, most of
      these effects are avoided. We compared the effects of topically applied
      aprotinin, tranexamic acid and placebo on postoperative bleeding and transfusion
      requirements. METHODS: In this single-center prospective, randomized, double
      blind trial, 300 adult cardiac patients were randomized into three groups to
      receive one million IU of aprotinin (AP group), 2.5g of tranexamic acid (TA
      group) or placebo (PL group) topically before sternal closure. Groups were
      comparable with respect to all preoperative and intraoperative variables.
      Postoperative bleeding, transfusion requirements and hematologic parameters were
      evaluated. RESULTS: Postoperative bleeding within first 12-h period (AP group
      433+/-294 [350; 360]ml, TA group 391+/-255 [350; 305]ml, PL group 613+/-505 [525;
      348]ml), as well as cumulative blood loss within 24h (AP group 726+/-432 [640;
      525]ml, TA group 633+/-343 [545; 335]ml, PL group 903+/-733 [800; 445]ml), showed
      statistically significant inter-group differences (both p<0.001). Bleeding rates
      values were significantly higher in placebo group compared to the groups treated
      with antifibrinolytic agents (AP and TA groups) concerning both variables.
      Although TA group showed the lowest values, no statistical differences between TA
      and AP groups were found. Inter-group difference of blood product requirements
      was not statistically significant. CONCLUSIONS: Topical use of either tranexamic
      acid or aprotinin efficiently reduces postoperative bleeding. TA seems to be at
      least as potent as aprotinin, but potentially safer and with better cost
      effectiveness ratio.

PMID- 17218111
TI  - Inducible cell death in plant immunity.
AB  - Programmed cell death (PCD) occurs during vegetative and reproductive plant
      growth, as typified by autumnal leaf senescence and the terminal differentiation
      of the endosperm of cereals which provide our major source of food. PCD also
      occurs in response to environmental stress and pathogen attack, and these
      inducible PCD forms are intensively studied due their experimental tractability.
      In general, evidence exists for plant cell death pathways which have similarities
      to the apoptotic, autophagic and necrotic forms described in yeast and metazoans.
      Recent research aiming to understand these pathways and their molecular
      components in plants are reviewed here.

PMID- 17218112
TI  - Renaturation and purification of ApxII toxin of Actinobacillus pleuropneumoniae.
AB  - ApxII toxin is the only Apx toxin that is produced by Actinobacillus
      pleuropneumoniae serotype 7. In order to determine whether the recombinant ApxII
      that derived from Escherichia coli (E. coli) expression is faithful to the
      natural ApxII so that can be used as additional component in vaccine preparation,
      the structure gene apxIIA of ApxII toxin was expressed in E. coli with
      prokaryotic expression vector pGEX-6p-1 (formed pGEX-6p-A). pGZRS-C which is A.
      pleuropneumoniae-E. coli shuttle vector pGZRS-38 expressing the post
      transcriptional activation gene apxII C was co-expressed with pGEX-6p-A. The
      expression product of rApxII A formed inclusion. The inclusion protein was
      oxidized, refolded and restored hemolytic activity after denaturation,
      renaturation and purification. The result indicated that E. coli expressed
      recombinant ApxII toxin has good fidelity, which makes it possible to produce
      this valuable antigen for vaccine preparation or diagnosis.

PMID- 17218114
TI  - A transglutaminase from Chinese shrimp (Fenneropenaeus chinensis), full-length
      cDNA cloning, tissue localization and expression profile after challenge.
AB  - Transglutaminase can catalyze the cross-linking reaction between soluble clotting
      protein molecules from the plasma for prevention of excess blood loss from a
      wound and obstructing micro-organisms from invading the wound in crustaceans. A
      novel transglutaminase (FcTG) gene was cloned from hemocytes of Chinese shrimp
      Fenneropenaeus chinensis by 3' and 5' rapid amplification of cDNA ends (RACE)
      PCR. The full-length cDNA consists of 2972bp, encoding 757 amino acids with a
      calculated molecular mass of 84.96kDa and a theoretical isoelectric point of
      5.61. FcTG contains a typical transglutaminase-like homologue (TGc domain: E
      value=1.94e-38). Three catalytic sites (Cys-324, His-391 and Asp-414) are present
      in this domain. The deduced amino acid sequence of FcTG showed high identity with
      black tiger shrimp TG, kuruma shrimp TG and crayfish TG. Transcripts of FcTG mRNA
      were mainly detected in gill, lymphoid organ and hemocytes by RT-PCR. RNA in situ
      hybridization further confirmed that FcTG was constitutively expressed in
      hemocytes both in the circulatory system and lymphoid organ. The variation of
      mRNA transcription level in hemocytes and lymphoid organ following injection of
      killed bacteria or infection with white spot syndrome virus (WSSV) was quantified
      by RT-PCR. The up-regulated expression of FcTG in shrimp lymphoid organ following
      injection of bacteria indicates that it is inducible and might be associated with
      bacterial challenge.

PMID- 17218113
TI  - Analysis of the orientation of primary cilia in growth plate cartilage: a
      mathematical method based on multiphoton microscopical images.
AB  - The chondrocytic primary cilium has been hypothesized to act as a mechano-sensor,
      analogously to primary cilium of cells in epithelial tissues. We hypothesize that
      mechanical inputs during growth, sensed through the primary cilium, result in
      directed secretion of the extracellular matrix, thereby establishing tissue
      anisotropy in growth plate cartilage. The cilium, through its orientation in
      three-dimensional space, is hypothesized to transmit to the chondrocyte the
      preferential direction for matrix secretion. This paper reports on the
      application of classical mathematical methods to develop an algorithm that
      addresses the particular challenges relative to the assessment of the orientation
      of the primary cilium in growth plate cartilage, based on image analysis of
      optical sections visualized by multiphoton microscopy. Specimens are prepared by
      rapid cold precipitation-based fixation to minimize possible artifactual post
      mortem alterations of ciliary orientation. The ciliary axoneme is localized by
      immunocytochemistry with antibody acetylated-alpha-tubulin. The method is
      applicable to investigation of ciliary orientation in different zones of the
      growth plate, under either normal or altered biomechanical environments. The
      methodology is highly flexible and adaptable to other connective tissues where
      tissue anisotropy and directed secretion of extracellular matrix components are
      hypothesized to depend on the tissue's biomechanical environment during
      development and growth.

PMID- 17218115
TI  - Simultaneous flow cytometric assessment for cellular types and phagocytic
      abilities of the haemocytes of the hard clam, Meretrix lusoria.
AB  - The aim of this study was to devise a simple protocol for flow cytometric
      analysis to separate various haemocytic populations of the hard clam Meretrix
      lusoria based on the mitochondrial membrane potential diversity detected by the
      fluorescence probe 3,3-dihexyloxacarbocyanine iodide (DiOC6). Compared with the
      traditional technique for separation of haemocytic populations, continuous
      Percoll gradient centrifugation, our novel method was more efficient and yielded
      a higher ratio in separating the clams' haemocytic populations. Based on
      fluorescence 1 (FL-1) and side scatter (SSC) analysis for haemocytes stained with
      various fluorescent densities of DiOC6 using flow cytometer, the data showed that
      there were three obvious cell regions R1, R2, and R3, identified by hyalinocytes,
      small granulocytes and large granulocytes, respectively. At the same time our
      results showed that the percentages of haemocytes in R1, R2, and R3 were 49.71+/
      0.65%, 19.35+/-00.74%, 30.94+/-0.69%, respectively. After classifying the
      haemocytic populations, phagocytic activity of the haemocytes was simultaneously
      analysed with phycoerythrin (PE)-labeled Vibrio vulnificus and detected by flow
      cytometry. Our results demonstrated that there were higher percentages of large
      granulocytes compared with hyalinocytes and the percentage of small granulocytes
      was related to the mitochondrial membrane potential and phagocytic activities.

PMID- 17218116
TI  - Activation of the shoulder and arm muscles during axial load exercises on a
      stable base of support and on a medicine ball.
AB  - The purpose of this study was to compare SEMG activities during axial load
      exercises on a stable base of support and on a medicine ball (relatively
      unstable). Twelve healthy male volunteers were tested (x=23+/-7 y). Surface EMG
      was recorded from the biceps brachii, anterior deltoid, clavicular portion of
      pectoralis major, upper trapezius and serratus anterior using surface
      differential electrodes. All SEMG data are reported as percentage of RMS mean
      values obtained in maximal voluntary contractions for each muscle studied. A 3
      way within factor repeated measures analysis of variance was performed to compare
      RMS normalized values. The RMS normalized values of the deltoid were always
      greater during the exercises performed on a medicine ball in relation to those
      performed on a stable base of support. The trapezius showed greater mean electric
      activation amplitude values on the wall-press exercise on a medicine ball, and
      the pectoralis major on the push-up. The serratus and biceps did not show
      significant differences of electric activation amplitude in relation to both
      tested bases of support. Independent of the base of support, none of the studied
      muscles showed significant differences of electric activation amplitude during
      the bench-press exercise. The results contribute to the identification of the
      levels of muscular activation amplitude during exercises that are common in
      clinical practice of rehabilitation of the shoulder and the differences in terms
      of type of base of support used.

PMID- 17218117
TI  - A new automated and high-throughput system for analysis of the forced swim test
      in mice based on magnetic field changes.
AB  - INTRODUCTION: MicroAct (Neuroscience, Tokyo, Japan) was originally developed as a
      new system for an automated analysis of scratching behaviors in mice. This system
      is based on the detection of electric current in the coils according to the
      movement of the magnets implanted in the hind paws. We applied and improved this
      system to establish an automated analysis system of forced swimming behaviors in
      mice, which is used as an animal model of depression. METHODS: One day before the
      test, male CD-1 mice were attached with a wire ring to their hind paws under
      inhalation anesthesia. After attaching a small magnet to both of the wire rings,
      each animal was placed for 6 min in a glass cylinder filled with water, which is
      surrounded by a coil. The swimming behaviors of the mouse were analyzed for the
      measurement of duration of immobility, a major marker of depression in rodents,
      by the detection system (MicroAct). The duration of immobility was also
      determined by manual measurement using the swimming behavior-recorded videotapes
      produced at the same time as the automated analysis. RESULTS: The difference of
      the duration of immobility between naive mice and mice with the rings was not
      significant. The dose-response effect of imipramine (tricyclic antidepressant, 0,
      7.5, 15, 30 and 60 mg/kg, p.o.) on the duration of immobility in the last 4-min
      of the 6-min testing period determined by MicroAct was similar to that assessed
      by the manual measurement. These data from the two different methods were
      significantly correlated (r=0.8805). Moreover, throughput of the automated
      analysis was 15 times more efficient than that of the manual analysis.
      DISCUSSION: These results suggest that the automated analysis system of forced
      swimming of mice using MicroAct can be used as a high-throughput method to
      examine antidepressive activity of a compound with objectivity and reliability.

PMID- 17218118
TI  - Observations on juvenile myoclonic epilepsy amongst ethnic Bengalees in West
      Bengal--an Eastern Indian State.
AB  - BACKGROUND: Juvenile myoclonic epilepsy (JME) is not too uncommonly encountered
      in Indian neurological practice. A number of reports from different parts of
      India have documented the clinical phenomenology and EEG characteristics of this
      genetically determined epileptic syndrome. However, no study has yet been
      reported from the Eastern part of India and none done so far in patients in a
      specific ethnic group. Furthermore therapy response and follow up data are not
      available in detail in the Indian studies. OBJECTIVE: To study disease
      expression, EEG characteristics and therapy response of JME patients in ethnic
      Bengalees in West Bengal, an Eastern Indian State, in a clinic based study.
      MATERIAL AND METHODS: 200 patients with JME attending the Neurology Department of
      the Institute have been followed up for 5 years and different parameters of
      disease expression as outlined above have been studied. RESULTS: Overall clinical
      disease expression has been found to be similar in this clinic based study in
      ethnic Bengalees as compared to other reports from India and elsewhere. About 16%
      of patients showed a relative resistance to Valproate therapy. Hundred percent of
      patients in whom therapy withdrawal was attempted, relapsed within<1-2 years.
      Amongst female patients (132), 16 developed features of polycystic ovarian
      syndrome while on Valproate therapy. In over half of them, the symptoms regressed
      after successful switch over from Valproate to Clobazam. 12/132 female patients
      became pregnant during follow up and while on Valproate; teratogenic effect was
      evident in only one such patient. CONCLUSIONS: Phenotypic variations in disease
      expression including therapy response have been noted within a single ethnic
      group of patients attending the clinic and might account for genetic
      heterogeneity noted in molecular genetic studies. JME cannot really be called a
      very 'benign' epileptic syndrome; recurrence after therapy withdrawal almost
      invariably occurs.

PMID- 17218119
TI  - Resolution 'scaling law' in MRI of articular cartilage.

PMID- 17218120
TI  - Retinal and olfactory bulb precursor cells show distinct responses to FGF-2 and
      laminin.
AB  - We analyzed whether the embryonic (E12.5-E14.5) mouse retina possesses genuine
      neural stem cells and how they respond to defined growth factors and
      extracellular matrix molecules. Whereas most combinations produced no or limited
      cell survival and proliferation in culture, FGF-2 plus heparin and laminin
      stimulated proliferation and the formation of aggregates composed, after two
      days, of 95.2% nestin-positive cells. However, cells in these aggregates could
      only be passaged poorly, lost nestin expression and proliferative capacity, and
      differentiated into neurons. Under the same conditions, olfactory bulb precursor
      cells divided efficiently and could be expanded. These data suggest that, in
      addition to FGF-2 and laminin, embryonic retinal neuroepithelial cells need
      additional extrinsic and/or intrinsic regulators to maintain cell proliferation
      and self-renewal.

PMID- 17218121
TI  - Immunohistochemical study of flotillin-1 in rat testis with ischemia/reperfusion
      injury.
AB  - To investigate the involvement of flotillin-1 in acute experimental testicular
      torsion, we examined the expression and cellular localization of flotillin-1 and
      cathepsin D in the rat testis with ischemia/reperfusion (I/R) injury. Western
      blot analysis showed that the expression of flotillin-1 increased significantly
      6h after I/R and that the level remained elevated for 48 h.
      Immunohistochemically, flotillin-1 was constitutively localized in some Sertoli
      cells, peritubular myoid cells, and interstitial cells in the normal testis.
      After I/R injury, Sertoli cells in the damaged tubules were intensely
      immunostained for flotillin-1 at 24 and 48 h after I/R. Flotillin-1 was also
      detected in some inflammatory cells in the interstitial space around damaged
      tubules. Furthermore, flotillin-1 was colocalized with cathepsin D, a lysosomal
      marker, in normal testis (mainly in Sertoli cells), and the colocalization was
      greater in Sertoli cells and macrophages in I/R injured testes. Therefore, we
      postulate that flotillin-1 immunoreactivity is increased in some Sertoli and
      inflammatory cells (especially in ED1-positive activated macrophages) in
      testicular torsion and that flotillin-1 in the injured testis associates with
      lysosomes in Sertoli cells and macrophages, activating subsequent signals in
      inflammatory macrophages and Sertoli cells after I/R.

PMID- 17218122
TI  - Purification and some properties of galectin-1 derived from water buffalo
      (Bubalus bubalis) brain.
AB  - An increasing number of galectins have been found in various animal species, the
      most abundant of which is galectin-1. The purpose of the present study was to
      purify and characterize galectin-1 from buffalo brain. We purified the galectin
      using a combination of ammonium sulphate fractionation and affinity
      chromatography and the homogeneity was determined by both native polyacrylamide
      gel electrophoresis (PAGE) and denaturing SDS-PAGE. The molecular weight of the
      galectin as determined by SDS-PAGE under reducing conditions and by gel
      filtration column under native conditions was 13.8 and 24.5 kDa, respectively,
      suggesting a dimeric form of galectin. The most potent inhibitor of the galectin
      activity was lactose, giving complete inhibition of hemagglutination at 0.8 mM.
      Galectin showed higher specificity towards human blood group A. Free thiol groups
      were estimated at a molar ratio of 2.9. The effects of alkylating reagents
      (iodoacetate and iodoacetamide) on saccharide binding of the galectin were
      studied. Both alkylating reagents significantly inactivated the activity of the
      galectin within 20 min. The temperature and pH stability of the galectin were
      determined. Our findings based on physico-chemical properties, carbohydrate and
      blood group specificities of the galectin may have future implications in
      biological and clinical applications.

PMID- 17218123
TI  - Hydrolytic activities of anaerobic fungi from wild blue bull (Boselaphus
      tragocamelus).
AB  - The anaerobic fungi play an active role in the plant fibre degradation by
      producing a wide array of potential hydrolytic enzymes in the rumen. In present
      study, 12 anaerobic fungal strains were isolated from the faecal samples of wild
      blue bull, and identified as species of Piromyces, Anaeromyces, Orpinomyces and
      Neocallimastix based on their morphological characteristics. Isolate WNG-12
      (Piromyces sp.), showed maximum filter paper cellulase (23 mIU ml(-1)) and
      xylanase (127 mIU ml(-1)) activity, while WNG-5 (Piromyces sp.) showed maximum
      carboxymethyl cellulase activity (231 mIU ml(-1)). Based on the results obtained,
      it can be stated that Piromyces sp. WNG-12 may be a promising isolate in
      utilizing fibre rich diets in the rumen as evidenced by the production of
      hydrolytic enzymes in vitro.

PMID- 17218124
TI  - Cystic tumor of the jugulodigastric triangle.

PMID- 17218125
TI  - The influence of lead thyroid collars on cephalometric landmark identification.
AB  - OBJECTIVE: To investigate whether the application of thyroid collars (TCs)
      affects cephalometric landmark identification. STUDY DESIGN: A randomized and
      observer-blinded diagnostic study with head films taken from 2 groups was
      undertaken, with 1 group wearing TCs during radiography (n = 100) and 1 group not
      wearing TCs (n = 100). The interobserver reproducibility of 15 landmarks was
      evaluated using 1-way analysis of variance and independent samples t test to
      compare the groups. RESULTS: The total mean error radius of the non-TC group
      (1.28 +/- 1.47 mm) was smaller (P < or = .001) than that of the TC group (1.57 +/
      1.58 mm). Three landmarks located on the hyoid bone and on the second and third
      cervical vertebrae were identified as the main confounding factors. CONCLUSIONS:
      Personal lead shielding of the thyroid gland affects landmark identification, but
      the overall clinical effect is negligible. Thyroid collars should be routinely
      applied during cephalometric radiography if cephalometric analyses are limited to
      structures above the second cervical vertebra.

PMID- 17218127
TI  - Separation of sequences from host-pathogen interface using triplet nucleotide
      frequencies.
AB  - The identification of genes involved in host-pathogen interactions is important
      for the elucidation of mechanisms of disease resistance and host susceptibility.
      A traditional way to classify the origin of genes sampled from a pool of mixed
      cDNA is through sequence similarity to known genes from either the pathogen or
      host organism or other closely related species. This approach does not work when
      the identified sequence has no close homologues in the sequence databases. In our
      previous studies, we classified genes using their codon frequencies. This method,
      however, explicitly required the prediction of CDS regions and thus could not be
      applied to sequences composed from the non-coding regions of genes. In this
      study, we show that the use of sliding-window triplet frequencies extends the
      application of the algorithm to both coding and non-coding sequences and also
      increases the prediction accuracy of a Support Vector Machine classifier from
      95.6+/-0.3 to 96.5+/-0.2. Thus the use of the triplet frequencies increased the
      prediction accuracy of the new method by more than 20% compared to our previous
      approach. A functional analysis of sequences detected gene families having
      significantly higher or lower probability to be correctly classified compared to
      the average accuracy of the method is described. The server to perform
      classification of EST sequences using triplet frequencies is available at (URL:
      http://mips.gsf.de/proj/est3).

PMID- 17218128
TI  - Partial silencing of a hydroxy-methylglutaryl-CoA reductase-encoding gene in
      Trichoderma harzianum CECT 2413 results in a lower level of resistance to
      lovastatin and lower antifungal activity.
AB  - In the present article, we describe the cloning and characterization of the
      Trichoderma harzianum hmgR gene encoding a hydroxymethylglutaryl CoA reductase
      (HMGR), a key enzyme in the biosynthesis of terpene compounds. In T. harzianum,
      partial silencing of the hmgR gene gave rise to transformants with a higher level
      of sensitivity to lovastatin, a competitive inhibitor of the HMGR enzyme. In
      addition, these hmgR-silenced transformants produced lower levels of ergosterol
      than the wild-type strain in a minimal medium containing lovastatin. The silenced
      transformants showed a decrease in hmgR gene expression (up to a 8.4-fold, after
      72h of incubation), together with an increase in the expression of erg7 (up to a
      15.8-fold, after 72h of incubation), a gene involved in the biosynthesis of
      triterpenes. Finally, hmgR-silenced transformants showed a reduction in their
      antifungal activity against the plant-pathogen fungi Rhizoctonia solani and
      Fusarium oxysporum.

PMID- 17218126
TI  - Cell cycle regulation in the developing lens.
AB  - Regulation of cell proliferation is a critical aspect of the development of
      multicellular organisms. The ocular lens is an excellent model system in which to
      unravel the mechanisms controlling cell proliferation during development. In
      recent years, several cell cycle regulators have been shown to be essential for
      maintaining normal patterns of lens cell proliferation. Additionally, many growth
      factor signaling pathways and cell adhesion factors have been shown to have the
      capacity to regulate lens cell proliferation. Given this complexity,
      understanding the cross talk between these many signaling pathways and how they
      are coordinated are important directions for the future.

PMID- 17218129
TI  - Hydrophobin genes and their expression in conidial and aconidial Neurospora
      species.
AB  - Homologs of the gene encoding the hydrophobin EAS from Neurospora crassa have
      been identified both in the other conidial species of Neurospora (N. discreta, N.
      intermedia, N. sitophila, and N. tetrasperma) and selected aconidial species (N.
      africana, N. dodgei, N. lineolata, N. pannonica, and N. terricola). Southern blot
      analysis indicated the presence of a single gene in all species examined. EAS
      like proteins were purified from the conidial species and each was shown to be
      the proteolytically processed gene-product of the corresponding eas homolog.
      While EAS-like proteins were not detected in the aconidial species, putative eas
      transcripts were detected in some isolates following RT-PCR and the aerial hyphae
      of these species were hydrophobic. DNA sequences of the coding region of the eas
      homologs were amplified by PCR and cloned and sequenced from all species except
      N. pannonica. Phylogenetic analysis of these sequences produced two clusters, the
      first comprising the conidiating species N. crassa, N. intermedia, N. sitophila,
      and N. tetrasperma forming a closely related group with N. discreta more distant,
      and the second comprising the aconidial species N. africana, N. dodgei, N.
      lineolata forming another closely related group with N. terricola more distant.

PMID- 17218130
TI  - Effects of age and allergen-induced airway inflammation in cats: radiographic and
      cytologic correlation.
AB  - Thoracic radiography is an important diagnostic tool for feline respiratory
      medicine. The aim of this study was (1) to assess age-related changes of thoracic
      radiographic views in healthy young cats and (2) to test if experimentally
      induced bronchial inflammation by inhaling Ascaris suum (AS) allergens leads to
      radiographic changes after single or repeated exposures. Healthy cats (n=15-30)
      aged between 6 and 30 months were evaluated. Eight healthy cats and eight AS
      sensitised cats, respectively, inhaled sterile saline or allergen. Radiographs
      were taken 24h before, and 6, 24 and 48 h after the challenge. Bronchoalveolar
      lavage (BAL) was performed after the last radiographic examination. AS-sensitised
      cats underwent three further allergen challenges at 3-month intervals. The
      radiographic evaluation was based on a scoring system considering bronchial,
      interstitial and alveolar patterns. A significant age-related increase in
      interstitial and total radiographic score was detected in healthy cats older than
      18 months and in healthy cats older than 24 months. Whilst saline inhalation did
      not affect radiographic scores, a single AS challenge induced significant changes
      of all scores within 6-24h. A significant positive correlation between
      radiographic scores and BAL neutrophils and eosinophils was found. Repeated AS
      challenges did not induce irreversible changes in radiographic scores.

PMID- 17218131
TI  - A minimal stress model for the assessment of electroacupuncture analgesia in rats
      under halothane.
AB  - The use of anesthetics in acupuncture analgesia is controversial. We evaluate a
      steady-state light anesthesia model to test whether minimal stress manipulation
      and reliable measurement of analgesia could be simultaneously achieved during
      electroacupuncture (EA) in animals. A series of experiments were performed.
      Firstly, EA compliance and tail-flick latencies (TFL) were compared in rats under
      0.1%, 0.3%, 0.5%, 0.7%, or 1.1% halothane for 120min. Under 0.5% halothane, TFL
      were then measured in groups receiving EA at intensity of 3, 10 or 20 volt (V), 1
      or 2mg/kg morphine, 20V EA plus naloxone, or control. Subsequently, the effect of
      EA on formalin-induced hyperalgesia was tested and c-fos expression in the spinal
      dorsal horn was analyzed. Rats exhibited profound irritable behaviors and highly
      variable TFL under 0.1% or 0.3% halothane, as well as a time-dependent increase
      of TFL under 0.7% or 1.1% halothane. TFL remained constant at 0.5% halothane, and
      needle insertion and electrical stimulation were well tolerated. Under 0.5%
      halothane, EA increased TFL and suppressed formalin-induced hyperalgesia in an
      intensity-dependent and naloxone-reversible manner. EA of 20V prolonged TFL by
      74%, suppressed formalin-induced hyperalgesia by 32.6% and decreased c-fos
      expression by 29.7% at the superficial and deep dorsal horn with statistically
      significant difference. In conclusion, 0.5% halothane provides a steady-state
      anesthetic level which enables the humane application of EA stimulus with the
      least interference on analgesic assessment. This condition serves as a minimal
      stress EA model in animals devoid of stress-induced analgesia while maintaining
      physiological and biochemical response in the experiment.

PMID- 17218132
TI  - Self-efficacy mediates the relation between pain-related fear and outcome in
      chronic low back pain patients.
AB  - This study aimed to determine whether self-efficacy beliefs mediated the relation
      between pain-related fear and pain, and between pain-related fear and disability
      in CLBP patients who exhibited high pain-related fear. In a cross-sectional
      design, 102 chronic low back pain (CLBP) patients completed measures for pain,
      disability, self-efficacy and pain-related fear (fear of movement and
      catastrophizing). Multistep regression analyses were performed to determine
      whether self-efficacy mediated the relation between pain-related fear and outcome
      (pain and/or disability). Self-efficacy was found to mediate the relation between
      pain-related fear and pain intensity, and between pain-related fear and
      disability. Therefore, this study suggests that when self-efficacy is high,
      elevated pain-related fear might not lead to greater pain and disability.
      However, in instances where self-efficacy is low, elevated pain-related fear is
      likely to lead to greater pain and disability. In view of these findings, we
      conclude that it is imperative to assess both pain-related fear and self-efficacy
      when treating CLBP patients with high pain-related fear.

PMID- 17218134
TI  - Spectral editing in solid-state MAS NMR of quadrupolar nuclei using selective
      satellite inversion.
AB  - A sensitivity enhancement method based on selective adiabatic inversion of a
      satellite transition has been employed in a (pi/2)CT-(pi)ST1-(pi/2)CT spectral
      editing sequence to both enhance and resolve multisite NMR spectra of quadrupolar
      nuclei. In addition to a total enhancement of 2.5 times for spin 3/2 nuclei,
      enhancements up to 2.0 times is reported for the edited sites in a mixture of
      rubidium salts.

PMID- 17218133
TI  - Analysis of nitroxide spin label motion in a protein-protein complex using
      multiple frequency EPR spectroscopy.
AB  - X- and W-band EPR spectra, at room and low temperatures, are reported for
      nitroxide spin labels attached to cysteine residues selectively introduced into
      two proteins, the DNase domain of colicin-E9 and its immunity protein, Im9. The
      dynamics of each site of attachment on the individual proteins and in the tight
      DNase-Im9 complex have been analysed by computer simulations of the spectra using
      a model of Brownian dynamics trajectories for the spin label and protein.
      Ordering potentials have been introduced to describe mobility of labels
      restricted by the protein domain. Label mobility varies with position from
      completely immobilised, to motionally restricted and to freely rotating. Bi-modal
      dynamics of the spin label have been observed for several sites. We show that W
      band spectra are particularly useful for detection of anisotropy of spin label
      motion. On complex formation significant changes are observed in the dynamics of
      labels at the binding interface region. This work reveals multi-frequency EPR as
      a sensitive and valuable tool for detecting conformational changes in protein
      structure and dynamics especially in protein-protein complexes.

PMID- 17218135
TI  - Lack of histamine type-1 receptors impairs the thermal response of respiration
      during hypoxia in mice (Mus musculus).
AB  - Thermoregulation and the hypoxic ventilatory response are modulated by histamine
      type-1 (H1) receptors in the brain. In this study, we tested the hypothesis that
      activation of H1 receptors is required for the thermal control of ventilation
      during normoxia and hypoxia, using conscious male wild-type and H1 receptor
      knockout (H1RKO) mice (Mus musculus). Under normoxic conditions, hyperthermia (39
      degrees C) decreased minute ventilation (V (E)) and oxygen consumption [Formula:
      see text] in both genotypes, suggesting that H1 receptors are not involved in
      thermal ventilatory control during normoxia. Pa(CO2) was unchanged in both
      hyperthermia and normothermia, suggesting that the thermal decrease in V (E) is
      optimized by metabolic demand. Acute hypoxic gas exposure (7% O(2)+3% CO(2) in
      N(2)) increased, and then decreased, V (E) in wild-type mice; this increase was
      augmented and sustained by hyperthermia. Hypoxic gas exposure reduced [Formula:
      see text] and [Formula: see text] in wild-type mice at both body temperatures;
      the reduced [Formula: see text] during combined hyperthermia and hypoxia was
      higher than during normothermia and hypoxia. In H1RKO mice, hyperthermia did not
      augment the V (E) response to hypoxia, and did not affect [Formula: see text] and
      [Formula: see text] during hypoxia. In conclusion, histamine participates in the
      thermal increase of ventilation during hypoxia by activating H1 receptors.

PMID- 17218136
TI  - Pregnancy-associated plasma protein-A (PAPP-A): a local regulator of IGF
      bioavailability through cleavage of IGFBPs.
AB  - Pregnancy-associated plasma protein-A (PAPP-A) was originally isolated in 1974,
      as one of four proteins of placental origin found in high concentrations in the
      blood of pregnant women. In the early 1990s several laboratories reported novel
      protease activity against insulin-like growth factor binding protein-4 (IGFBP-4)
      in media conditioned by several cell types. This activity was unique, as it
      appeared to require the presence of IGF to cleave IGFBP-4. In 1999, this IGF
      dependent IGFBP-4 protease activity was isolated from human fibroblast
      conditioned media and identified as PAPP-A. Subsequently, PAPP-A was shown to be
      expressed by a variety of cell types, and thus no longer could be considered to
      be just "pregnancy-associated". This review will describe what is currently known
      about the structure of PAPP-A and about its function as an IGFBP protease, with a
      focus on new insights obtained through study of a PAPP-A knock-out mouse model
      and on potential clinical applications.

PMID- 17218137
TI  - [Impact of nutrition management in patients with head and neck cancers treated
      with irradiation: is the nutritional intervention useful?].
AB  - AIMS: The head and neck tumors are most often associated with a precarious
      nutritional status. Radiotherapy increases the risk of denutrition because of its
      secondary effects on the secretory and sensorial mucous membranes. The purpose of
      our retrospectively study was to evaluate the interest of a precocious and
      regular nutritional therapy on the ability to maintain the nutritional status of
      the patient during the radiotherapy. PATIENTS AND METHODS: The fifty-two patients
      included in the survey have been classified retrospectively in two different
      groups based on their observance to the nutritional therapy: group 1 "good
      observance", group 2 "bad observance". RESULTS: The 31 patients of group 1 have
      lost an average of 1.9 kg by the end of the irradiation, whereas the 21 patients
      of group 2 have lost an average of 6.1 kg (p<0.001). The almost stability in
      weight of patients in group 1 was linked to a lower frequency of breaks in the
      radiotherapy (6 vs 33% p=0.03) and in a decrease in grade of inflammatory mucous
      membranes (10% of grade 3 in group 1 vs 52% in group 2, p=0.006). The quantity of
      calories ingested in form of nutritional supplements was greater in group 1 and
      consequently enabled patients to stabilized their weight (1200 calories in group
      1 versus 850 calories in group 2, p<0.005). CONCLUSIONS: The given nutritional
      advice and the prescription of adapted nutritional supplements consequently
      allowed limiting efficiently the weight lost during the irradiation and the grade
      of mucositis. The systematization of a precocious nutritional therapy for
      patients irradiated for head and neck tumors seems absolutely essential.

PMID- 17218138
TI  - Determination and analysis of the DNA sequence of highly attenuated herpes
      simplex virus type 1 mutant HF10, a potential oncolytic virus.
AB  - A spontaneously occurring herpes simplex virus type 1 (HSV-1) mutant, designated
      HF10, replicates very efficiently and induces extensive cell fusion in most
      transformed cells as well as Vero cells, but is highly attenuated in mice when
      inoculated by peripheral routes of infection. Recent studies have shown that HF10
      is a promising agent for use in oncolytic virotherapy. In this study, we
      sequenced the genome of HF10 and compared it with that of HSV-1 strain 17, a
      reference strain with the syn+ phenotype. The sequencing covered whole regions
      corresponding to all open reading frames of strain 17, and the overall putative
      amino acid identity between HF10 and strain 17 was 99.1% except for proteins
      encoded by three genes with frame-shift mutations. HF10 had a number of deletions
      and insertions in the genome, resulting in the lack of the functional expression
      of UL43, UL49.5, UL55, UL56 and latency-associated transcripts. Additionally,
      HF10 had amino acid changes in genes involved in the regulation of syncytium
      formation, including UL1, UL20, UL22, UL24, UL27 and UL53. The proteins encoded
      by UL1, UL2, UL11, UL44, US1, US7, US8.5, US10 and US12 exhibited a relatively
      high divergence. These data provide the genetic background of HF10 and insight
      into the molecular mechanism of HSV-1 replication and pathogenicity.

PMID- 17218139
TI  - Raynaud's phenomenon.
AB  - Vascular acrosyndromes constitute a common reason for physician visits. They are
      associated with connective tissue disease; for example, 90% of patients with
      scleroderma experience Raynaud's phenomenon. The rheumatologist must strive to
      establish the diagnosis, to identify a potential underlying cause, and to
      prescribe effective treatment when the symptoms are incapacitating. Raynaud's
      phenomenon is the acrosyndrome most commonly encountered by rheumatologists. The
      diagnosis of Raynaud's phenomenon rests on clinical grounds. Nailfold
      capillaroscopy and immunological tests are useful chiefly for determining the
      cause. Calcium-channel antagonists are the treatment of reference for Raynaud's
      phenomenon. Drugs introduced over the last few years for severe refractory forms
      include prostacyclin and its derivatives, endothelin receptor antagonists, and
      phosphodiesterase inhibitors. These drugs were developed as a result of new
      knowledge on the pathogenesis of Raynaud's phenomenon. Acrocyanosis, which is
      extremely common, and erythromelalgia are the other main vascular acrosyndromes.

PMID- 17218140
TI  - Spondylodiscitis: an unusual complication after lumbar myelography.

PMID- 17218141
TI  - Investigations for bone metastasis from an unknown primary.
AB  - OBJECTIVES: To evaluate the respective contributions of various investigations
      used to identify the primary tumor in a cohort of patients referred for
      diagnostic evaluation of one or more bone metastases. METHODS: A single-center
      retrospective study was conducted in a cohort of patients admitted between
      October 1990 and January 2000 for evaluation of one or more bone metastases with
      no known primary. All patients underwent radionuclide bone scanning, a chest
      radiograph, and an abdominal ultrasound scan. Computed tomography (CT) of the
      chest and abdomen, CT of the brain, and tumor marker assays were performed as
      clinically indicated. Using the final diagnosis as the reference standard, we
      evaluated the diagnostic usefulness of each investigation. RESULTS: The 152
      patients (104 men and 48 women) had a mean age of 63.5+/-12.5 years. The primary
      was located in the lung in 37 patients, prostate in 26, breast or female genital
      tract in 24, urinary system in 11, gastrointestinal tract in 11, head and neck in
      6, and other organs in 4. In 33 patients, no primary was identified. The
      extraskeletal metastases were located chiefly in the liver (20.4%), lung (17.1%),
      pleura (13.2%), and brain (7.2%). Bone biopsies were performed in 107 patients:
      84 had a single bone biopsy, 16 had two bone biopsies, and 7 had three bone
      biopsies. The first bone biopsy was taken in the rheumatology department with or
      without fluoroscopic guidance in 62 patients, in the radiology department under
      CT guidance in 6 patients, and in the surgery department in 32 patients; this
      information was unavailable for the 7 remaining patients. The first bone biopsy
      was taken from the iliac bone in 48 patients, spine in 32, sacrum in 10, rib in
      3, and other sites in 7. The histological biopsy findings indicated
      adenocarcinoma in 58 cases, epidermoid carcinoma in 28 cases, undifferentiated
      carcinoma in 2 cases, and other histological patterns in 9 cases. In 80 patients,
      another metastatic site was easier to access than the bone metastasis. Tumor
      marker assays were of limited value for determining the site of the primary, with
      the exception of prostate-specific antigen. CONCLUSION: Bone biopsies performed
      by rheumatologists, generally under fluoroscopic guidance, usually indicate the
      site of the primary or at least the histological type. Tumor markers are often
      positive but are of limited usefulness for identifying the primary.

PMID- 17218142
TI  - [Arch and sentinel: surgical technique of sentinel node biopsy with the
      axillopectoral muscle].
AB  - OBJECTIVE: Identify the axillopectoral muscle (usually called Langer's axillary
      arch) and know the main surgical techniques of axillary sentinel node biopsies.
      PATIENTS AND METHODS: We present the results of our five-year clinical
      prospective study: the presence of this anomaly is diagnosed peroperatively
      during a sentinel node biopsy. RESULTS: Langer's arch is identified in 1,7%,
      often with an unilateral distribution. Lymph nodes are just near or behind the
      muscle. Sentinel node biopsy dissection is difficult in about 40%. DISCUSSION AND
      CONCLUSION: The embryological derivation and anatomical features of this muscle
      are described, with emphasis on the surgical applications. Its presence or
      absence should be ascertained in every sentinel node biopsy because of the risks
      of axillary dissection complications by this ectopic muscle.

PMID- 17218143
TI  - [Multiple recurrent papillomas of the breast: case report].
AB  - We report the case of a patient presenting multiple recurrent papillomas of the
      breast. This mild mammary pathology, developed at the expense of the
      galactophoric ducts, recurred four times, in a nodular way, in spite of in sano
      surgical resection. The retrospective study of the cell proliferation and the DNA
      quantification of the cells constitutive of the papillomas, on several samples,
      underlined evolutive lesions, which could be predictive of a malignant
      degeneration. This observation allows us to discuss the management of this rare
      mild mammary pathology, which can sometimes lead to invasive breast carcinoma.

PMID- 17218144
TI  - X-chromosome polymorphism on DXS8378, DXS7132, HPRTB and DXS7423 loci in 130
      individuals from Brescia (northern Italy).
AB  - One hundred and thirty unrelated individuals (80 females and 50 males) from
      Brescia (northern Italy) were typed for DXS8378, DXS7132, HPRTB and DXS7423 loci.
      Allele, genotype and haplotype frequencies were calculated. A comparison between
      our population data and others from Caucasians and Asians populations was
      performed.

PMID- 17218145
TI  - Ultrasonic bubbles in medicine: influence of the shell.
AB  - Ultrasound contrast agents consist of microscopically small bubbles encapsulated
      by an elastic shell. These microbubbles oscillate upon ultrasound insonification,
      and demonstrate highly nonlinear behavior, ameliorating their detectability.
      (Potential) medical applications involving the ultrasonic disruption of contrast
      agent microbubble shells include release-burst imaging, localized drug delivery,
      and noninvasive blood pressure measurement. To develop and enhance these
      techniques, predicting the cracking behavior of ultrasound-insonified
      encapsulated microbubbles has been of importance. In this paper, we explore
      microbubble behavior in an ultrasound field, with special attention to the
      influence of the bubble shell. A bubble in a sound field can be considered a
      forced damped harmonic oscillator. For encapsulated microbubbles, the presence of
      a shell has to be taken into account. In models, an extra damping parameter and a
      shell stiffness parameter have been included, assuming that Hooke's Law holds for
      the bubble shell. At high acoustic amplitudes, disruptive phenomena have been
      observed, such as microbubble fragmentation and ultrasonic cracking. We analyzed
      the occurrence of ultrasound contrast agent fragmentation, by simulating the
      oscillating behavior of encapsulated microbubbles with various sizes in a
      harmonic acoustic field. Fragmentation occurs exclusively during the collapse
      phase and occurs if the kinetic energy of the collapsing microbubble is greater
      than the instantaneous bubble surface energy, provided that surface instabilities
      have grown big enough to allow for break-up. From our simulations it follows that
      the Blake critical radius is not a good approximation for a fragmentation
      threshold. We demonstrated how the phase angle differences between a damped
      radially oscillating bubble and an incident sound field depend on shell
      parameters.

PMID- 17218146
TI  - Determination of suitable sample sizes for multi-patient based finite element
      studies.
AB  - Finite element analysis is used extensively to assess joint replacements, but the
      majority of these are single sample studies. Recent investigations have suggested
      that such studies are unable to account for natural inter-patient variation in
      bone geometry and material property distribution. Recent developments in computer
      tomography based analyses make multiple sample studies possible; the question
      remains how many femurs are required to perform a study which accounts for such
      variations. This work investigates the factors that should be considered in
      answering this question. It explores sample sizing techniques when comparing
      strain distribution in the intact and implanted femur and when comparing two or
      more implant designs in a group of femurs. An example analysis of the effect of
      femoral head resurfacing was undertaken. Two sample sizing calculations were
      utilised, one based on achieving the desired precision in results, the other
      based on determining if a significant difference exists between two designs. The
      analysis shows that reasonable statistical precision can be achieved with a group
      of femurs. The study was also able to determine a suitable sample size for the
      analysis of a statistically significant difference between two groups of femurs
      with varying design parameters. The study concluded that while sample sizing is
      recommended for an accurate analysis, consideration must be made for the
      practicality of such a task.

PMID- 17218147
TI  - Knowledge-based interpolation of curves: application to femoropopliteal arterial
      centerline restoration.
AB  - We present a novel algorithm, Partial Vector Space Projection (PVSP), for
      estimation of missing data given a database of similar datasets, and demonstrate
      its use in restoring the centerlines through simulated occlusions of
      femoropopliteal arteries, derived from CT angiography data. The algorithm
      performs Principal Component Analysis (PCA) on a database of centerlines to
      obtain a set of orthonormal basis functions defined in a scaled and oriented
      frame of reference, and assumes that any curve not in the database can be
      represented as a linear combination of these basis functions. Using a database of
      centerlines derived from 30 normal femoropopliteal arteries, we evaluated the
      algorithm, and compared it to a correlation-based linear Minimum Mean Squared
      Error (MMSE) method, by deleting portions of a centerline for several occlusion
      lengths (OL: 10 mm, 25 mm, 50 mm, 75 mm, 100 mm, 125 mm, 150 mm, 175 mm and 200
      mm). For each simulated occlusion, we projected the partially known dataset on
      the set of basis functions derived from the remaining 29 curves to restore the
      missing segment. We calculated the maximum point-wise distance (Maximum Departure
      or MD) between the actual and estimated centerline as the error metric. Mean
      (standard deviation) of MD increased from 0.18 (0.14) to 4.35 (2.23) as OL
      increased. The results were fairly accurate even for large occlusion lengths and
      are clinically useful. The results were consistently better than those using the
      MMSE method. Multivariate regression analysis found that OL and the root-mean
      square error in the 2 cm proximal and distal to the occlusion accounted for most
      of the error.

PMID- 17218149
TI  - Perceptions and behaviour of access of the Internet: a study of women attending a
      breast screening service in Sydney, Australia.
AB  - OBJECTIVES: To describe the perceptions and behaviour in accessing health
      information from the Internet by women attending a BreastScreen, New South Wales
      (NSW) Service in Northern Sydney. DESIGN: Cross-sectional study. SETTING: A
      BreastScreen NSW Service in Northern Sydney. MAIN OUTCOME MEASURES: Behaviour and
      perceptions of accessing of the Internet for breast health and screening
      information and other related health information. PARTICIPANTS: Four hundred and
      fifteen women aged > or =40 years who had a screening mammogram at a BreastScreen
      NSW Service in Northern Sydney. Data were collected from 1 October to 22 December
      2004 (study interval). RESULTS: Four hundred and sixty-one eligible women were
      invited to participate in the study and of these 415 women agreed to participate
      in the study (participation rate=90%). Of the 415 women enrolled in the cohort,
      80% (333/415) of women accessed the Internet in general and 62% (205/333) of the
      women who accessed the Internet also accessed health related information from the
      Internet, but only 7% of the total women accessed breast health and screening
      information from the Internet. Two hundred and eighty (70%) women in the cohort
      expressed their intention to access the Internet if they were diagnosed with
      breast cancer. Age (OR=0.94; 95% CI=0.91-0.97), marital status (OR=2.65; 95%
      CI=1.45-4.83), educational status (OR=3.26; 95% CI=1.77-6.02) and behavioural
      intention of accessing the Internet if diagnosed with breast cancer (OR=3.31; 95%
      CI=1.83-5.98) were found to be associated with access of Internet for general
      information. Furthermore, behavioural intention (OR=2.43; 95% CI=1.30-4.55),
      rating of computer skills as 'average' (OR=0.42; 95% CI=0.22-0.79) and 'not good
      to poor' (OR=0.23; 95% CI=0.11-0.49) were found to be associated with access of
      health related information from the Internet. CONCLUSIONS: Information searching
      from the Internet is common among women having a screening mammogram. There is
      potential to provide guidance to women regarding accessing the BreastScreen NSW
      website and other reliable sources of Internet information on breast health,
      breast screening and cancer-related information.

PMID- 17218150
TI  - Prevalence of ECG abnormalities in an international survey of patients with
      suspected or confirmed heart failure at death or discharge.
AB  - BACKGROUND: Most patients suspected of having heart failure (HF) will get a 12
      lead electrocardiogram (ECG) but its utility for excluding HF or assisting in its
      management has rarely been investigated. METHODS: The EuroHeart Failure survey
      identified 11,327 patients hospitalised with a suspected diagnosis of HF from 115
      hospitals in 24 countries. ECGs were obtained from 9315 patients, of whom 5934
      had cardiac imaging tests. The utility of the ECG was assessed for excluding or
      diagnosing major structural heart disease (MSHD) or major left ventricular
      systolic dysfunction (MLVSD) and for therapeutic decision making. FINDINGS: MSHD
      was present in 70% and MLVSD in 54% of patients overall but in only 21% and 5%,
      respectively, if the ECG was entirely normal. However, <2% of patients had a
      normal ECG. No single ECG characteristic identified a probability <25% of MSHD or
      <20% of MLVSD. Patients with QRS width >or=120 ms or anterior pathological Q
      waves had a probability >80% of MSHD and >70% of MLVSD. Diagnostic models
      suggested that electrocardiographic criteria alone were not accurate for the
      diagnosis or exclusion of important heart disease in this population. However,
      2468 patients (42%) had an electrocardiographic finding that should be used to
      guide the choice of therapy. CONCLUSIONS: A normal ECG is rare in patients with
      suspected HF but has limited diagnostic value in this setting. The ECG has an
      important role in guiding therapy.

PMID- 17218151
TI  - A mathematical analysis of SELEX.
AB  - Systematic evolution of ligands by exponential enrichment (SELEX) is a procedure
      by which a mixture of nucleic acids that vary in sequence can be separated into
      pure components with the goal of isolating those with specific biochemical
      activities. The basic idea is to combine the mixture with a specific target
      molecule and then separate the target-NA complex from the resulting reaction. The
      target-NA complex is then separated by mechanical means (for example by
      filtration), the NA is then eluted from the complex, amplified by polymerase
      chain reaction (PCR) and the process repeated. After several rounds, one should
      be left with a pool of [NA] that consists mostly of the species in the original
      pool that best binds to the target. In Irvine et al. [Irvine, D., Tuerk, C.,
      Gold, L., 1991. SELEXION, systematic evolution of nucleic acids by exponential
      enrichment with integrated optimization by non-linear analysis. J. Mol. Biol.
      222, 739-761] a mathematical analysis of this process was given. In this paper we
      revisit Irvine et al. [Ibid]. By rewriting the equations for the SELEX process,
      we considerably reduce the labor of computing the round to round distribution of
      nucleic acid fractions. We also establish necessary and sufficient conditions for
      the SELEX process to converge to a pool consisting solely of the best binding
      nucleic acid to a fixed target in a manner that maximizes the percentage of bound
      target. The assumption is that there is a single nucleic acid binding site on the
      target that permits occupation by not more than one nucleic acid. We analyze the
      case for which there is no background loss (no support losses and no free [NA]
      left on the support). We then examine the case in which such there are such
      losses. The significance of the analysis is that it suggests an experimental
      approach for the SELEX process as defined in Irvine et al. [Ibid] to converge to
      a pool consisting of a single best binding nucleic acid without recourse to any a
      priori information about the nature of the binding constants or the distribution
      of the individual nucleic acid fragments.

PMID- 17218152
TI  - Soluble MICA as an independent prognostic factor for the overall survival and
      progression-free survival of multiple myeloma patients.
AB  - Major histocompatibility complex class I-related chain A (MICA) molecules are
      frequently expressed in lymphoproliferative malignancies including multiple
      myeloma (MM). MICA activates NK cells and co-stimulates T cells by interaction
      with its immunoreceptor NKG2D. In contrast, soluble MICA (sMICA) molecules impair
      the functions of NKG2D(+) T and NK cells, which may facilitate tumor cell escape
      from immunosurveillance. Here, we analyzed the clinical relevance of sMICA in 97
      MM patients. sMICA (mean+/-SEM pg/ml) was significantly increased (p<0.0001) in
      patients (429+/-20) compared to controls (230+/-20; N=43). Serial determination
      showed a strong correlation between increments of sMICA and paraprotein levels
      (r=0.543, p<0.0001, N=49). sMICA levels >305 pg/ml are associated with a poor
      overall (p=0.004) and progression-free survival (p=0.002). Multivariate analysis
      revealed sMICA as an independent predictive factor for overall (p=0.007) and
      progression-free survival (p=0.002). Thus, our results suggest sMICA as a potent
      prognostic marker in MM, which may be useful to identify risk patients.

PMID- 17218153
TI  - Circulating nitric oxide and C-reactive protein levels in Indian kala azar
      patients: correlation with clinical outcome.
AB  - Interferon gamma (IFN-gamma) and nitric oxide (NO) are the major players of the
      host defense against Leishmania. In the present study circulating levels of IFN
      gamma, NO, interleukin (IL)-6 and C-reactive protein (CRP) were compared in kala
      azar (KA), post-kala azar dermal leishmaniasis (PKDL) and healthy controls. A
      significantly elevated level of these parameters was evident in KA compared to
      PKDL or control. Further, significantly elevated levels of IFN-gamma, NO and CRP
      were observed in sodium antimony gluconate (SAG) unresponsive cases compared to
      responsive cases. In PKDL cases, NO was significantly elevated while other
      parameters were comparable to control. At post-treatment stage, KA patients
      showed a significant decrement in all the parameters, however, IL-6 and CRP
      remained above control level. Hence, data implies that the parasites survive in
      spite of the presence of effector molecules, and the excessive release of IFN
      gamma and NO could be associated with the progression of the disease.

PMID- 17218154
TI  - Oral feeding of Bifidobacterium bifidum (BGN4) prevents CD4(+) CD45RB(high) T
      cell-mediated inflammatory bowel disease by inhibition of disordered T cell
      activation.
AB  - Probiotics have been considered as preventive agents for the control of
      inflammatory bowel disease (IBD). In this study, we assessed the immunomodulatory
      effect of Bifidobacterium bifidum BGN4 on the control of IBD using the CD4(+)
      CD45RB(high) T cell transfer disease model. The mice were fed for 4 weeks with
      either a conventional diet containing only skim milk or a diet containing skim
      milk with 0.3% (w/w) BGN4. The BGN4-fed mice showed normal weight growth, fewer
      clinical symptoms such as thickened wall and inflammatory cell infiltration, and
      lower levels of CD4(+) T lymphocyte infiltration and inflammatory cytokine
      productions than the skim milk-fed mice with IBD in the large intestine.
      Suppression of these cytokine productions, particularly IFN-gamma and MCP-1,
      through BGN4 treatment was also observed in the in vitro co-culture between
      intestinal epithelial cells and T cells. These findings suggested that a BGN4
      supplemented diet could be helpful for the control of aberrant immune responses
      in the intestinal tissue.

PMID- 17218155
TI  - Employment concerns of people with epilepsy in Kerala, south India.
AB  - We examined current employment status, reasons for unemployment, and related
      psychosocial concerns of 202 persons with epilepsy from the south Indian state of
      Kerala. Compared with 19% of the general population, 58% of persons with epilepsy
      were unemployed. Seizure remission for > or = 2 years, monotherapy, better
      education, ability to travel alone, and ability to drive were significantly
      associated with being employed. More than three-fourths of the persons with
      epilepsy had disclosed their epilepsy to their employers and co-workers, which
      did not adversely affect employment for the majority. The unemployed perceived
      fear of having seizures and seizure-related falls in the workplace, inadequate
      education, and antiepileptic drug-induced fatigue as reasons for unemployment. We
      conclude that unemployment is a major concern of people with epilepsy in this
      developing region. In addition to optimum seizure control, persons with epilepsy
      need support in job seeking, in reducing fear of seizures and falls in the
      workplace, and in identifying their individual abilities and limitations.

PMID- 17218156
TI  - Mental health problems in children and adolescents referred to a national
      epilepsy center.
AB  - This study aimed to investigate the occurrence of psychiatric morbidity in
      children and adolescents referred to a tertiary national epilepsy center
      (inpatient unit) and the extent of the unmet need for psychiatric services in
      this group. Participants were 74 children and adolescents aged 9-15 referred from
      February 2001 to October 2002 (67% response rate). The multi-informant (parent,
      teacher, self-report) Strengths and Difficulties Questionnaires (SDQs) were
      answered before or at admission. Patients with severe mental retardation or
      pervasive developmental disorder were excluded. We found a large proportion (77%)
      with a possible or probable psychiatric disorder. The parents, teachers, and
      adolescents themselves had higher mean SDQ scores than a British community sample
      on total difficulties, emotional symptoms, conduct problems, hyperactivity
      inattention, peer problems, and impairment, but not self-reported conduct
      problems. Nearly 80% of the children who probably had a psychiatric disorder had
      no contact with the psychiatric service.

PMID- 17218157
TI  - Fluctuating Kluver-Bucy syndrome in a child with epilepsy due to bilateral
      anterior temporal congenital malformations.
AB  - An 11-year-old boy with epilepsy due to congenital bilateral anterior temporal
      lobe malformations presented with fluctuating Kluver-Bucy syndrome (KBS). Since
      the age of 2, he had experienced clusters of three or four daily complex partial
      seizures over 2-3 days in a month, followed by a seizure-free interval of 3-4
      weeks. During the seizure-free period, the patient exhibited hyperorality,
      sniffing, irritability alternating with placidity, anxiety, unsolicited sexual
      gestures, and unusual calmness after eating. KBS features escalated up to the
      onset of the seizure cluster, and remitted after the seizures. Brain MRI revealed
      bilateral anterior temporal cortical dysplasia with enlarged and dysmorphic
      amygdalar-hippocampal complex. Brain [(18)F]fluorodeoxyglucose positron emission
      tomography PET showed bilateral anterior and mesial temporal hypometabolism.
      Video/EEG monitoring revealed independent right and left temporal lobe seizures.
      This is the first reported case of KBS due to congenital bitemporal
      malformations. Also, KBS behavior phenotype in this patient fluctuated, with
      escalation during the seizure-free period and remission induced by the monthly
      seizure cluster. This fluctuating pattern could represent forced normalization.

PMID- 17218158
TI  - Oxidative damage and anti-oxidant capacity in two migratory bird species at a
      stop-over site.
AB  - We quantified in the garden warbler (Sylvia borin) and the barn swallow (Hirundo
      rustica), two long-distance migratory songbirds, the early oxidative damage
      (ROMs) and plasma anti-oxidant capacity (OXY) variation of individuals caught at
      a stop-over site after a sustained flight across the sea, during spring
      migration. Our main goal was to quantify the oxidative damage and anti-oxidant
      capacity variation in these two migratory species in relation to fat and muscle
      stores. The birds were sampled in Ponza, a small island along the migratory route
      of these species. The levels of ROMs and OXY did not show any differences between
      the two species and in general were higher in individuals with higher fat and
      protein stores. Nevertheless, the balance between ROMs and OXY was better in
      individuals in good condition. These patterns were similar in both species. No
      sex differences emerged for both ROMs and OXY in the barn swallow, the only
      species that could be sexed. Both markers of oxidative stress did not show any
      significant variation across a 30-min restrained experiment. These data are the
      first of this kind in wild birds in a migratory context and suggest that
      individuals in better condition are exposed to lower oxidative stress, providing
      an indirect evidence of the oxidative cost caused by prolonged flights.

PMID- 17218159
TI  - Peptides of arachnid venoms with insecticidal activity targeting sodium channels.
AB  - Arachnids have a venom apparatus and secrete a complex chemical mixture of low
      molecular mass organic molecules, enzymes and polypeptide neurotoxins designed to
      paralyze or kill their prey. Most of these toxins are specific for membrane
      voltage-gated sodium channels, although some may also target calcium or potassium
      channels and other membrane receptors. Scorpions and spiders have provided the
      greatest number of the neurotoxins studied so far, for which, a good number of
      primary and 3D structures have been obtained. Structural features, comprising a
      folding that determines a similar spatial distribution of charged and hydrophobic
      side chains of specific amino acids, are strikingly common among the toxins from
      spider and scorpion venoms. Such similarities are, in turn, the key feature to
      target and bind these proteins to ionic channels. The search for new insecticidal
      compounds, as well as the study of their modes of action, constitutes a current
      approach to rationally design novel insecticides. This goal tends to be more
      relevant if the resistance to the conventional chemical products is considered. A
      promising alternative seems to be the biotechnological approach using toxin
      expressing recombinant baculovirus. Spider and scorpion toxins having
      insecticidal activity are reviewed here considering their structures, toxicities
      and action mechanisms in sodium channels of excitable membranes.

PMID- 17218160
TI  - Endothelial injury in the initiation and progression of vascular disorders.
AB  - Endothelial cell dysfunction is considered to be an early event which
      subsequently leads to vascular wall disorders. Ultrastructural studies indicate
      that the endothelial cell changes involve membrane damage, increased
      permeability, swelling and necrosis. The endothelial cell loss of function could
      be as a result of changes in hemodynamic forces (shear and/or hoop stress),
      direct drug-induced cytotoxicity, mechanical device implant-induced injury and/or
      immune-mediated mechanisms. Drugs may perturb endothelial cell integrity by
      directly triggering inflammatory signaling cascades, enhancing expression of
      cellular adhesion molecules, activation of cytotoxic T cells and/or
      autoantibodies directed against endothelial cell membranes. Local release of
      inflammatory cytokines and chemokines activate endothelial cells to upregulate
      soluble adhesion molecules, activate neutrophils and generate reactive oxygen
      species which serve to amplify the initial inflammation leading to dysregulated
      apoptosis, secondary necrosis and overt vascular injury lesions. Considering the
      role of the endothelium in the initiation and propagation of vascular wall
      injury, there is a need for the discovery of validated biomarkers to serve as a
      predictor of activation of inflammatory cascades in the development of vascular
      injury. This article reviews some aspects of the multifaceted mechanisms that
      lead to the initial endothelial cell disruption and subsequent vascular wall
      injury.

PMID- 17218161
TI  - Cirrhosis, spontaneous venous thromboses, and splenic gas gangrene.

PMID- 17218162
TI  - New and emerging treatment of chronic hepatitis B.
AB  - Conventional treatment of chronic hepatitis B with interferon alfa-2b,
      lamivudine, and adefovir is limited by low rates of sustained hepatitis B virus
      DNA suppression and hepatitis B e antigen (HBeAg) seroconversion, increasing
      rates of drug resistance to the oral agents, and poor tolerability of interferon.
      Recently several promising new antiviral agents have emerged that possess potent
      antiviral effects, less toxicity, and have little or no risk of drug resistance.
      Two new agents, entecavir and peginterferon alfa-2a, have received recent
      approval by regulatory authorities in the United States and several other
      countries for the treatment of adults with chronic hepatitis B. In large phase
      III clinical trials, these agents have demonstrated superior efficacy over
      lamivudine in both HBeAg-positive and HBeAg-negative patients. Drug resistance
      occurs at a low rate in lamivudine-refractory patients treated with entecavir or
      is, to date, nonexistent in nucleoside-naive patients treated with entecavir and
      all patients receiving peginterferon. In addition, several novel agents in
      clinical development, such as emtricitabine, clevudine, telbivudine,
      valtorcitabine, and tenofovir, have shown promising clinical profiles in patients
      with chronic hepatitis B. This review summarizes the recent clinical studies of
      these new agents and discusses the implications of these data for the management
      of chronic hepatitis B.

PMID- 17218163
TI  - Influence of positive family history on clinical characteristics of functional
      constipation.
AB  - BACKGROUND & AIMS: We observed that there is familial aggregation in patients
      with functional constipation. Their clinical characteristics have not been
      studied. The aim of this study was to investigate the clinical characteristics of
      patients with functional constipation with and without a positive family history.
      METHODS: Patients with functional constipation satisfying Rome II criteria were
      recruited. A Rome II questionnaire on constipation was given to the patients'
      families to identify whether there were any family members with idiopathic
      constipation. The clinical characteristics between those with and without
      positive family history were evaluated. RESULTS: There were 118 patients with at
      least one first-degree relative with idiopathic constipation and 114 patients
      without a positive family history. The patients in the 2 groups were comparable
      in mean age (P = .3) and sex distribution (P = .09). Patients with positive
      family history had a younger age of onset (median, 11-20 years vs 21-30 years, P
      < .0001); longer duration of constipation (20 +/- 14 vs 15 +/- 13, P = .016);
      more complications, eg, symptomatic hemorrhoids, anal fissure, and rectal
      prolapse (54.2% vs 40.4%, P = .034); less precipitating factors leading to the
      onset of constipation (35.6% vs 49.1%, P = .037); more frequent use of digital
      evacuation (27.1% vs 13.2%, P = .008), but no difference in the association with
      psychological disorders (P = .3); transit time (P = .5); or manometric
      dyssynergia (P = .5). CONCLUSIONS: Patients with idiopathic constipation and with
      a positive family history exhibited different clinical characteristics. This
      might be related to the early age of onset of the symptoms, which might, in turn,
      give clues to the underlying etiology.

PMID- 17218164
TI  - Clinicopathologic features of the severe form of acute type 1 autoimmune
      hepatitis.
AB  - BACKGROUND & AIMS: Acute onset autoimmune hepatitis (acute AIH) is difficult to
      diagnose by using serologic data. In addition, some patients with the severe form
      of acute AIH do not respond to immunosuppressive therapy and have a poor outcome.
      In this study, we analyzed the clinicopathologic features of patients who were
      diagnosed as having acute AIH. METHODS: Retrospective review of patients with
      presumed acute AIH at Ehime University Graduate School of Medicine was performed.
      RESULTS: In liver tissue, infiltrates in the portal area and plasma cell
      infiltration are more common in acute AIH compared with acute hepatitis caused by
      other causes. Patients with acute AIH who did not have severe jaundice at the
      time of diagnosis exhibited a very good response to corticosteroid therapy,
      despite lower titers of antinuclear antibody (ANA). Most patients with acute AIH
      with higher levels of bilirubin and titers of ANA in sera respond poorly to
      corticosteroid therapy. CONCLUSIONS: Histologic findings might be useful for the
      early diagnosis of acute AIH. Acute AIH patients with high levels of bilirubin
      and high titers of ANA in sera often do not respond to corticosteroid therapy.

PMID- 17218165
TI  - Acalculous cholecystitis.

PMID- 17218166
TI  - Costs of recruiting couples to a clinical trial.
AB  - Multiple barriers contribute to the slow recruitment of participants to research
      studies, which in turn extends the time required to translate promising
      scientific discoveries into proven therapeutic interventions. A small but growing
      literature is developing on the extraordinary costs of recruiting participants to
      studies, and thereby demonstrating that underestimating the cost of participant
      recruitment can contribute to these recruitment problems. These recruitment
      challenges and costs are exacerbated when the participants' study eligibility is
      determined by relatively narrowly defined illness parameters. Recruitment
      challenges are further compounded when dyads (two individuals engaged in a
      sociologically significant relationship, such as husbands and wives, siblings or
      extended families) must be recruited to an illness-focused study. For these
      latter groups, there are no data to guide researchers in how to anticipate those
      participant recruitment costs. This paper describes the staff costs for a variety
      of strategies used to recruit participants to a randomized supportive care study
      for couples who were within 18 months of a prostate cancer diagnosis. Pegged to
      the value of the U.S. dollar for the period, the average cost of staff time was
      $288 per recruited and enrolled dyad, plus a promised additional $100 incentive
      for study retention. Within the strategies used, the staff costs per recruited
      dyad ranged from $152 to $1688. Accrual per strategy ranged from 0 to 107
      enrolled couples. When asked for secondary sources of information about the
      study, many participants reported more than one source of study referral,
      reflective of the multifaceted recruitment strategies deployed. In spite of
      innovative, culturally competent, and broad based recruitment methods, attainment
      of a diverse sample was difficult to accomplish in this study. Having estimates
      of the actual cost of recruiting dyads to research studies can help investigators
      prepare realistic study budgets.

PMID- 17218167
TI  - Cell cycle inhibitor, p19INK4d, promotes cell survival and decreases chromosomal
      aberrations after genotoxic insult due to enhanced DNA repair.
AB  - Genome integrity and cell proliferation and survival are regulated by an
      intricate network of pathways that includes cell cycle checkpoints, DNA repair
      and recombination, and programmed cell death. It makes sense that there should be
      a coordinated regulation of these different processes, but the components of such
      mechanisms remain unknown. In this report, we demonstrate that p19INK4d
      expression enhances cell survival under genotoxic conditions. By using p19INK4d
      overexpressing clones, we demonstrated that p19INK4d expression correlates with
      the cellular resistance to UV treatment with increased DNA repair activity
      against UV-induced lesions. On the contrary, cells transfected with p19INK4d
      antisense cDNA show reduced ability to repair DNA damage and increased
      sensitivity to genotoxic insult when compared with their p19INK4d-overexpressing
      counterparts. Consistent with these findings, our studies also show that p19INK4d
      overexpressing cells present not only a minor accumulation of UV-induced
      chromosomal aberrations but a lower frequency of spontaneous chromosome
      abnormalities than p19INK4d-antisense cells. Lastly, we suggest that p19INK4d
      effects are dissociated from its role as CDK4/6 inhibitor. The results presented
      herein support a crucial role for p19INK4d in regulating genomic stability and
      overall cell viability under conditions of genotoxic stress. We propose that
      p19INK4d would belong to a protein network that would integrate DNA repair,
      apoptotic and checkpoint mechanisms in order to maintain the genomic integrity.

PMID- 17218168
TI  - Role of active site tyrosines in dynamic aspects of DNA binding by AP
      endonuclease.
AB  - AP endonuclease (AP endo), a key enzyme in repair of abasic sites in DNA, makes a
      single nick 5' to the phosphodeoxyribose of an abasic site (AP-site). We recently
      proposed a novel mechanism, whereby the enzyme uses a key tyrosine (Tyr(171)) to
      directly attack the scissile phosphate of the AP-site. We showed that loss of the
      tyrosyl hydroxyl from Tyr(171) resulted in dramatic diminution in enzymatic
      efficiency. Here we extend the previous work to compare binding/recognition of AP
      endo to oligomeric DNA with and without an AP-site by wild type enzyme and
      several tyrosine mutants including Tyr(128), Tyr(171) and Tyr(269). We used
      single turnover and electrophoretic mobility shift assays. As expected, binding
      to DNA with an AP-site is more efficient than binding to DNA without one. Unlike
      catalytic cleavage by AP endo, which requires both hydroxyl and aromatic moieties
      of Tyr(171), the ability to bind DNA efficiently without an AP-site is
      independent of an aromatic moiety at position 171. However, the ability to
      discriminate efficiently between DNA with and without an AP-site requires
      tyrosine at position 171. Thus, AP endo requires a tyrosine at the active site
      for the properties that enable it to behave as an efficient, processive
      endonuclease.

PMID- 17218170
TI  - Pyrolytic carbon proximal interphalangeal joint arthroplasty: results with
      minimum two-year follow-up evaluation.
AB  - PURPOSE: To retrospectively review the surgical technique, postoperative
      therapy/splinting protocols, and clinical and radiographic outcomes of patients
      who had pyrolytic carbon proximal interphalangeal (PIP) joint arthroplasty.
      METHODS: A total of 50 PIP joint replacements in 35 patients were performed with
      a minimum follow-up period of 27 months. Indications for surgery included pain,
      decreased range of motion, instability, and/or deformity. The preoperative
      diagnosis was osteoarthritis in 14, rheumatoid arthritis in 11, and posttraumatic
      arthritis in 10. There were 20 women and 15 men affected. The average age at the
      time of surgery was 53 years. The fingers replaced included the index (15),
      middle (18), ring (10), and small (7). The preoperative arc of motion averaged 40
      degrees (0 degrees-60 degrees ), and the pinch and grip measurements averaged 3
      and 19 kg, respectively. The preoperative pain scores averaged 6 (scale, of 0-10)
      on a visual analog space scale. RESULTS: The arc of motion was 47 degrees after
      surgery, and the average pinch and grip measurements were 4 and 25 kg,
      respectively. Pain scores improved to 1. At the final follow-up evaluation the
      overall patient satisfaction was nearly 80%. The results of index finger PIP
      replacements are compatible with other digits. Fourteen joints (in 14 patients)
      to date have required additional procedures to improve or maintain joint
      motion/function or pain; 5 for minor reasons and 9 for major complications. The
      revision arthroplasty rate was 8%. No infections were noted. Although not
      medically necessary, 2 patients requested and had an amputation. Radiographic
      subsidence and subsequent settling (in accordance with Wolff's law) without
      apparent loosening occurred in 20 joints. CONCLUSIONS: Our 2-year minimum follow
      up evaluation of pyrolytic carbon implant arthroplasty showed improved pain
      relief and good overall patient satisfaction. Twenty-eight percent of patients
      required a second procedure and 8% required a revision arthroplasty. Radiographs
      showed gross changes in implant and eventual settling to a stable position in 40%
      of the joints. A longer follow-up period will help to better determine the
      efficacy of this implant. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic, Level IV.

PMID- 17218171
TI  - A new abductor pollicis longus suspension arthroplasty.
AB  - PURPOSE: Surgical treatment of osteoarthritis of the first carpometacarpal joint
      aims to achieve complete pain relief with restoration of thumb strength and
      stability. The aim of this study was to introduce a variation of the abductor
      pollicis longus (APL) sling arthroplasty and to determine its efficacy in
      comparison with other tendon sling arthroplasty procedures. METHODS: Between
      January 1999 and December 2003, 104 trapeziectomies in 74 consecutive patients
      (30 bilateral cases) were performed using a new APL sling arthroplasty. Patients
      were evaluated at 6 and 12 months after surgery. The outcomes were analyzed
      subjectively by questionnaire and objectively by clinical and radiographic
      evaluation. RESULTS: After 6 months, excellent results in terms of pain relief
      were achieved in 95 thumbs (91%) of 65 patients. The remaining 9 thumbs had
      ongoing pain and had a secondary surgery performed between 6 and 12 months after
      the initial surgery. Pain relief was achieved in 1 thumb by scaphotrapezoid
      arthrodesis and in the other 8 thumbs by excision of the osteophyte on the ulnar
      volar surface of the base of the first metacarpal, which was impinging on the
      base of the second metacarpal or the trapezoid. The gap was filled with a
      palmaris tendon anchovy. After 12 months, the 65 patients with successful
      trapeziectomies and APL sling remained pain-free. In these patients tip pinch,
      key pinch, and power grip strength increased by 46%, 19%, and 41%, respectively,
      from the preoperative values. In the 35 unilateral cases, tip pinch, key pinch,
      and power grip strength increased from 53%, 77%, and 65% of the contralateral
      hand strength before surgery to 82%, 89%, and 90%, respectively. CONCLUSIONS:
      This modified APL sling arthroplasty is a new and effective way of creating a
      suspension sling with the APL tendon after trapeziectomy, with results comparable
      or better than other published methods, for the treatment of osteoarthritis of
      the first carpometacarpal joint. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic,
      Level IV.

PMID- 17218172
TI  - Hematoma and distraction arthroplasty for thumb basal joint osteoarthritis:
      minimum 6.5-year follow-up evaluation.
AB  - PURPOSE: Although hematoma and distraction arthroplasty has been found to be
      successful in the treatment of thumb basal joint arthritis in the short term,
      questions about its efficacy in the long term have been raised. The goal of the
      present study was to evaluate the results of this procedure in patients at least
      6.5 years after surgery. METHODS: Twenty-two thumbs from 22 patients from a
      single surgeon's practice were entered into a prospective single-arm study for
      surgical treatment of basal thumb arthritis. Treatment consisted of piecemeal
      excision of the entire trapezium and 5 weeks of K-wire immobilization of the
      thumb metacarpal in opposition and slight distraction. No ligament reconstruction
      or tendon interposition was used. Motion, strength, standardized dexterity tests,
      stress radiographs, and outcome questionnaires including the Arthritis Impact
      Measurement Scales 2 were evaluated before surgery and at 6, 24, and at least 79
      months after surgery. RESULTS: At 6 months after surgery, 17 of 22 patients
      reported complete pain relief, and at the most recent follow-up evaluation
      (average, 88 months after surgery) 18 patients were entirely pain free. Range-of
      motion evaluation at the most recent follow-up evaluation showed 21 of 22 thumbs
      adducted fully into the plane of the palm, and 21 of 22 opposed to the small
      finger metacarpal head. Comparisons between preoperative and the recent
      postoperative strength measurements showed an average of 21% increase in grip
      strength and tip pinch strength, and an 11% increase in key pinch strength over
      preoperative values. Although the radiographically determined scaphoid-thumb
      metacarpal distance decreased with time from surgery, no correlation with
      strength or functional outcome measurements was found. The Arthritis Impact
      Measurement Scales 2 data showed postoperative improvement in the hand and finger
      function and arthritis pain scales. CONCLUSIONS: After trapezial excision, K-wire
      immobilization in a slightly overcorrected position without formal interposition
      or ligament reconstruction allows for restoration and maintenance of a stable,
      pain-free thumb that has comparable strength and motion with published reports of
      more complicated interventions over comparable time periods. TYPE OF STUDY/LEVEL
      OF EVIDENCE: Therapeutic, Level IV.

PMID- 17218173
TI  - Immunohistochemical analysis of wrist ligament innervation in relation to their
      structural composition.
AB  - PURPOSE: To analyze ligament innervation and the structural composition of wrist
      ligaments to investigate the potential differences in sensory and biomechanical
      functions. METHODS: The ligaments analyzed were the dorsal radiocarpal, dorsal
      intercarpal, scaphotriquetral, dorsal scapholunate interosseous,
      scaphotrapeziotrapezoid, radioscaphoid, scaphocapitate, radioscaphocapitate, long
      radiolunate, short radiolunate, ulnolunate, palmar lunotriquetral interosseous,
      triquetrocapitate, and triquetrohamate ligaments. The ligaments were harvested
      from 5 cadaveric, fresh-frozen specimens. By using the immunohistochemical
      markers p75, Protein Gene Product 9.5, and S-100 protein, the mechanoreceptors
      and nerve fibers could be identified. RESULTS: The innervation pattern in the
      ligaments was found to vary distinctly, with a pronounced innervation in the
      dorsal wrist ligaments (dorsal radiocarpal, dorsal intercarpal, scaphotriquetral,
      dorsal scapholunate interosseous), an intermediate innervation in the volar
      triquetral ligaments (palmar lunotriquetral interosseous, triquetrocapitate,
      triquetrohamate), and only limited/occasional innervation in the remaining volar
      wrist ligaments. The innervation pattern also was reflected in the structural
      differences between the ligaments. When present, mechanoreceptors and nerve
      fibers were consistently found in the loose connective tissue in the outer region
      (epifascicular region) of the ligament. Hence, ligaments with abundant
      innervation had a large epifascicular region, as compared with the ligaments with
      limited innervation, which consisted mostly of densely packed collagen fibers.
      CONCLUSIONS: The results of our study suggest that wrist ligaments vary with
      regard to sensory and biomechanical functions. Rather, based on the differences
      found in structural composition and innervation, wrist ligaments are regarded as
      either mechanically important ligaments or sensory important ligaments. The
      mechanically important ligaments are ligaments with densely packed collagen
      bundles and limited innervation. They are located primarily in the radial, force
      bearing column of the wrist. The sensory important ligaments, by contrast, are
      richly innervated although less dense in connective tissue composition and are
      related to the triquetrum. The triquetrum and its ligamentous attachments are
      regarded as key elements in the generation of the proprioceptive information
      necessary for adequate neuromuscular wrist stabilization.

PMID- 17218174
TI  - Carpal kinematics after proximal row carpectomy.
AB  - PURPOSE: Proximal row carpectomy (PRC) is a clinically useful motion-sparing
      procedure for the treatment of certain degenerative conditions of the wrist.
      Clinical outcome studies after PRC have shown that wrist flexion-extension
      averages approximately 60% of that of the contralateral wrist. The purpose of
      this study was to determine how the kinematics of the wrist are altered after
      PRC. METHODS: Eight fresh-frozen cadaver forearms were scanned with computed
      tomography before and after PRC. Forearms were scanned in 5 different wrist
      positions (neutral, extension, flexion, radial deviations, and ulnar deviation).
      Wrists were positioned dynamically and then held statically in a custom fixture
      through forces applied to the 4 wrist flexor/extensor tendon groups. Three
      dimensional computer models of the radius, lunate, and capitate were generated
      from the computed tomographic images, and the kinematics of the capitate and
      lunate were calculated relative to the neutral position. For the intact wrist,
      the motion of the capitate was calculated relative to both the lunate (midcarpal
      motion) and the radius (overall wrist motion) and the motion of the lunate was
      calculated relative to the radius (radiocarpal motion). After PRC, only the
      movement of the capitate relative to the radius was calculated, which represents
      radiocapitate and overall wrist motion. All motions were plotted in 3 dimensions
      for purposes of qualitative visualization. RESULTS: After PRC, the capitate
      articulated with the lunate fossa of the radius for all positions in all samples.
      Overall wrist motion decreased 28%, 30%, 40%, and 12% in flexion, extension,
      radial deviation, and ulnar deviation, respectively. Motion at the radiocarpal
      joint after PRC, however, was greater compared with motion at the radiocarpal and
      midcarpal joints of the intact wrist during flexion and extension. This was not
      the case in radial deviation because of impingement of the trapezoid on the
      radial styloid. In radial and ulnar deviation, motion of the capitate head
      changed from predominantly rotational in the intact wrist (midcarpal joint) to a
      combination of rotation and translation after PRC (radiocarpal joint).
      CONCLUSIONS: Removal of the proximal carpal row decreased normal wrist flexion
      and extension. Although ulnar deviation was preserved, radial deviation was
      limited by impingement of the trapezoid on the radial styloid. Radiocapitate
      range of motion after PRC was greater than capitolunate range of motion in the
      intact wrists. Compared with previously published requirements, wrist range of
      motion observed after PRC was sufficient for activities of daily living.

PMID- 17218175
TI  - The clinical implications of scaphotrapezium-trapezoidal arthritis with
      associated carpal instability.
AB  - PURPOSE: Common causes of dorsal intercalated segment instability (DISI) include
      scapholunate dissociations and scaphoid fracture nonunions. Although less common
      than these, scaphotrapezium-trapezoidal (STT) osteoarthritis (OA) may also be
      associated with the development of a DISI deformity. The clinical implications of
      this form of carpal instability in cases of STT arthritis are still unknown. To
      study the radiographic progression and incidence of this entity, we reviewed our
      patients and report on 24 wrists with DISI in the presence of STT arthritis.
      METHODS: A retrospective chart and radiographic review was performed on all
      patients seen between 1994 and 2004, with the diagnosis of STT arthritis to
      identify a subgroup of patients with DISI deformity on the presenting
      radiographs. Patients' clinical and surgical courses were noted. Postoperative
      radiographic changes were recorded, as were clinical outcomes. RESULTS: Sixteen
      patients with 24 wrists having STT arthritis and DISI deformity on presenting
      radiographs were identified. The median STT arthritis grade was 3.0 based on a
      modified Eaton and Glickel grading system. The median radiolunate angle was -21
      degrees of dorsal tilt. All patients had normal scapholunate angles. Abnormal
      scaphoid extension was seen in 19 of 24 wrists as measured by the radioscaphoid
      angle. Concomitant carpometacarpal arthritis was seen in 67% (n = 16) of the
      wrists, and midcarpal arthritis was identified in 50% (n = 8) of patients.
      Fifteen wrists required surgery for the symptoms and were followed up for a mean
      of 29 months after surgery. In the surgical group the radiolunate angles
      increased by mean of 6 degrees after surgery. Four of the 15 wrists required
      revisional surgery for persistent pain. CONCLUSIONS: Patients with STT arthritis
      may present with carpal instability that is not related to radiographic
      scapholunate instability. This instability is characterized by a normal
      scapholunate angle with an extension stance of the scaphoid and lunate. Midcarpal
      arthritis may be present. Surgical intervention for patients with STT arthritis
      and DISI deformity may lead to radiographic progression of midcarpal instability.

PMID- 17218176
TI  - Severity of scapholunate instability is related to joint anatomy and congruency.
AB  - PURPOSE: To determine whether the bony architecture of the distal radius and
      proximal scaphoid have a role in stabilizing the scaphoid, and to determine
      whether a relationship between the bony geometry measurements and the amount of
      wrist constraint could be determined. METHODS: Eight cadaver wrists were tested
      in a wrist joint motion simulator. The level of scapholunate instability after
      sectioning the scapholunate interosseous, radioscaphocapitate, and the
      scaphotrapezium ligaments was determined and related to radiographic measurements
      of volar tilt, lateral tilt (ulnar tilt of the radioscaphoid fossa), the depth of
      the radioscaphoid fossa, and 6 radii of curvature measurements of the proximal
      scaphoid and distal radius. The force to dorsally dislocate the scaphoid out of
      the radioscaphoid fossa was computed. RESULTS: The radioscaphoid fossa and
      scaphoid curvatures were larger in those wrists that did not show gross
      instability after ligamentous sectioning in the wrist simulator. Similarly, those
      wrists with a deeper radioscaphoid fossa and greater volar tilt were also more
      stable. The force required to dislocate these wrists was greater than in those
      wrists that showed gross carpal instability. CONCLUSIONS: This study suggests
      that the bony anatomy of the radius and scaphoid have a role in stabilizing the
      carpus after ligament injury. The effect of ligament sectioning on producing
      carpal instability may be moderated by the bone geometry of the radiocarpal
      joint. This may explain why some people may have a tear of the scapholunate
      interosseous ligament but not present with clinical symptoms.

PMID- 17218177
TI  - Computed tomography of suspected scaphoid fractures.
AB  - PURPOSE: Computed tomography (CT) can be used to triage suspected scaphoid
      fractures. This study assessed intraobserver and interobserver reliability and
      positive and negative predictive values of CT for the diagnosis of a nondisplaced
      scaphoid fracture. METHODS: Eight observers evaluated CT scans from 30 patients
      (13 with nondisplaced scaphoid fractures, 17 with no scaphoid fractures) for the
      presence or absence of a fracture. Five observers evaluated the scans a second
      time. Statistical analyses included intraobserver and interobserver reliability
      and diagnostic characteristics. RESULTS: Computed tomography had substantial
      intraobserver and interobserver reliability for the diagnosis of a nondisplaced
      scaphoid fracture. The average sensitivity, specificity, and accuracy of CT for a
      nondisplaced scaphoid fracture were 89%, 91%, and 90% for the first round and
      97%, 85%, and 88% for the second round of observations, respectively. Based on an
      estimated prevalence of 5% true fractures among patients with suspected scaphoid
      fractures, the average positive predictive value for the detection of
      radiographically occult scaphoid fractures with tomography of the wrist was 0.28.
      The average negative predictive value was 0.99. CONCLUSIONS: Computed tomography
      should be used with caution for triage of nondisplaced scaphoid fractures because
      false-positive results occur, perhaps from misinterpretation of vascular
      foraminae or other normal lines in the scaphoid. Given the relative infrequency
      of true fractures among patients with suspected scaphoid fractures, CT is better
      for ruling out a fracture than for ruling one in.

PMID- 17218178
TI  - Intra-articular pressure measurement in the radioulnocarpal joint using a novel
      sensor: in vitro and in vivo results.
AB  - PURPOSE: To determine the amount and distribution of forces transmitted across
      the human radioulnocarpal joint under physiologic conditions in vivo. We
      performed an in vitro validation of a specifically developed capacitive pressure
      sensor device and an in vivo measurement of force transmission and pressure
      distribution at the radioulnocarpal joint in a healthy volunteer. METHODS: A new
      capacitive pressure-sensor device was adapted for intra-articular pressure
      measurement in the human radioulnocarpal joint. The technical characteristics of
      the device were determined and the sensor was validated in fresh-frozen cadaver
      tests. Force transmission across the radioulnocarpal joint then was measured in
      healthy volunteers under local anesthesia. RESULTS: The sensor delivered
      reproducible measurements of forces across the radioulnocarpal joint and their
      distribution in the cadaver experiment. In vivo, 2 centers of force transmission
      were identified. None of these centers correlated with previous findings in the
      literature. More force is transmitted across the ulnar side of the
      radioulnocarpal joint than previously thought. The results are consistent with
      clinical findings. CONCLUSIONS: The novel sensor device is suitable for intra
      articular pressure measurement in the human radioulnocarpal joint in vitro and in
      vivo.

PMID- 17218179
TI  - Predictors of functional outcomes after surgical treatment of distal radius
      fractures.
AB  - PURPOSE: Identifying predictors of outcomes is important in anticipating and
      treating patients with underlying factors that may affect recovery. The
      predictors of functional outcomes after distal radius fracture (DRF) treatment
      have not been well defined in the past. METHODS: This was a prospective cohort
      study designed to identify predictors of hand outcomes after DRF treatment. The
      study included consecutive patients with inadequately reduced DRFs who had open
      reduction and internal fixation with volar plating. Demographic and socioeconomic
      data were collected at the time of the initial treatment. Outcome data were
      collected 3, 6, and 12 months after surgery. Outcome evaluation consisted of
      radiographic measurements and the Michigan Hand Outcomes Questionnaire (MHQ). We
      hypothesized that the following factors are important predictors of functional
      outcomes: (1) age, (2) socioeconomic status, (3) severity of fracture pattern,
      and (4) postsurgical radiographic measurements. Regression models were developed
      using the overall MHQ score as the outcome variable at 3 months and 1 year after
      surgery. RESULTS: Sixty-six patients had data available at 3 months and 49
      patients had data available at 1 year. At 3 months after surgery, radiographic
      incongruity (step + gap) was a significant predictor after controlling for age,
      fracture type, dorsal-volar tilt angulation, and income. Patients with increased
      incongruity reported lower MHQ scores (worse functional outcomes). At 1 year
      after surgery, however, only age and income were significant predictors after
      controlling for fracture type. Increased age and decreased income were associated
      with lower MHQ scores. CONCLUSIONS: After successful surgery and hand therapy,
      only age and income were significantly associated with long-term outcomes 1 year
      after surgery. Precise anatomic reduction enhances short-term functional outcomes
      in DRF treatment. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic, Level I.

PMID- 17218180
TI  - Responsiveness of the Michigan Hand Outcomes Questionnaire and physical
      measurements in outcome studies of distal radius fracture treatment.
AB  - PURPOSE: Outcomes study of distal radius fracture (DRF) treatment has been
      hampered by an uncertainty regarding the most appropriate outcomes assessment
      tool to evaluate the effectiveness of treatment. This study aimed to measure the
      responsiveness of the Michigan Hand Outcomes Questionnaire (MHQ) and physical
      measurements to assess the value of these outcomes tools for DRF studies.
      METHODS: Forty-seven patients prospectively completed the MHQ and physical
      testing at 3 months and 6 months (period 1) after open reduction and internal
      fixation of unstable DRFs. Thirty-seven patients prospectively completed the MHQ
      and physical testing at 6 months and 1 year after open reduction and internal
      fixation (period 2). Responsiveness to clinical change within each period was
      calculated with standardized response means (SRMs). RESULTS: In period 1, all
      domains of the MHQ except aesthetics significantly improved. The SRMs were large
      for the overall score and for the work domain. The SRMs were medium for the pain,
      function, and activities of daily living domains. In period 1, the grip strength,
      pinch strength, and active wrist range of motion measurements significantly
      improved and had large SRMs. In period 2, the grip- and pinch-strength tests
      significantly improved and the SRMs were medium, whereas the active wrist range
      of motion had a small SRM. CONCLUSIONS: Unlike other conditions such as carpal
      tunnel syndrome, for which the outcomes questionnaire is the most responsive
      measure, in DRF treatment both the MHQ and physical tests are responsive in
      measuring outcomes and should be reported for outcomes studies of DRFs. The MHQ
      and physical tests can be used for outcomes research related to DRF with the
      advantage of also being useful for assessing and comparing outcomes for other
      hand disorders.

PMID- 17218181
TI  - Impairment and disability after severe hand injuries with multiple phalangeal
      fractures.
AB  - PURPOSE: Upper-extremity impairment evaluation is performed mostly by using
      guidelines provided by the American Medical Association (AMA). Recently,
      subjective disability tests, such as the Disability of the Arm, Shoulder, and
      Hand (DASH) questionnaire, have been developed that appreciate the limitations
      patients experience in everyday life. In this study, the correlation between
      impairment and disability was assessed after treatment for severe hand injuries
      with multiple phalangeal fractures, with adjustment for comorbidity and follow-up
      duration. METHODS: The functional recovery of patients suffering severe hand
      trauma was evaluated using AMA impairment rating tests and DASH disability
      questionnaire scores. RESULTS: Seventy-eight patients with 228 phalangeal
      fractures were available for testing, with a mean follow-up period of 7.5 years.
      No statistically significant correlation existed between the AMA impairment
      ratings for the hand and the DASH module scores. There were weak correlations
      between the AMA impairment ratings for the arm and total body and the DASH module
      function scores. CONCLUSIONS: The lack of a strong correlation emphasizes the
      clear distinction between impairment and disability. The inclusion of disability
      outcome measures in the evaluation of hand trauma regimens might help to expand
      the clinician's view to more individualized, activity-of-daily-living-oriented,
      treatment regimens.

PMID- 17218182
TI  - Contralateral C7 transfer for the treatment of brachial plexus root avulsions in
      children - a report of 12 cases.
AB  - PURPOSE: To retrospectively determine the risks and benefits of contralateral C7
      nerve root transfer in infants and children. METHODS: In 12 infants and children
      with brachial plexus root avulsions from birth injury or other trauma, the common
      trunk of the contralateral C7 root was transferred to the trunk, division, cord,
      or nerve branch(es) on the affected side with 2 different types of interposition
      grafts. The surgery was performed in 1 stage for 5 patients and in 2 stages for 7
      patients. RESULTS: Patients were followed up for a mean of 42 months, with a
      minimum of 21 months. Noteworthy function (> or = M2+, modified British Medical
      Research Council grading system) was gained in 10 of 12 patients and sensory
      function (> or = S3, British Medical Research Council grading system) was gained
      in all patients. Improvements in strength and sensation were accompanied by
      little synchronous motion and sensibility changes in the donor limb in 7
      children, to whom the repaired nerves were those innervating the shoulder and/or
      elbow or both the musculocutaneous and median nerves. In addition to slight
      damage to the sensory function of the median nerve, 2 infants also had
      temporarily reduced shoulder abduction on the healthy side. CONCLUSIONS: For
      contralateral C7 transfer in infants and children with brachial plexus root
      avulsions, the deficit created by the procedure is minimal and motor and sensory
      function is gained. Transfer of the contralateral C7 root to different nerves for
      a child may improve the quality of functional recovery. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic, Level IV.

PMID- 17218183
TI  - Pharmacologic approaches to composite tissue allograft.
AB  - This article discusses the pharmacologic approaches and the most promising new
      compounds for composite tissue allograft tolerance. Although some approaches rely
      on a combination of immunosuppressive agents that act synergistically against
      rejection, other strategies use immunologic manipulation, including major
      histocompatibility complex matching, induction of chimerism, and use of
      monoclonal antibodies to abrogate the immune response. There is still a need,
      however, to reproduce these findings in species phylogenetically closer to
      humans. This may be the target of future research efforts, which may overcome the
      challenge of limb and face transplant rejection.

PMID- 17218184
TI  - Dry arthroscopy of the wrist: surgical technique.
AB  - PURPOSE: To present a method to perform arthroscopic exploration and
      instrumentation without infusing any fluid. METHODS: The hand is suspended from a
      bow, with traction on all fingers. Portals are developed as in the classic (wet)
      wrist arthroscopic procedure except that no water is infused to distend the joint
      and create the optic cavity. For this procedure the joint must be dried; we use
      suction through the synoviotomes and neurosurgical patties to accomplish this.
      RESULTS: We have performed more than 100 wrist arthroscopies using the dry
      technique without any undue difficulty. CONCLUSIONS: The dry technique is as
      effective as the classic procedure, without the cumbersome leakage of water or
      the risk of compartment syndrome. It allows some sophisticated arthroscopic
      procedures to be performed that would be impracticable with water. In addition
      from these benefits, if open surgery is performed after the arthroscopic
      exploration then the tissue planes are dry, making surgery much easier. The
      technique is believed to be inappropriate if thermal probes are used. A learning
      curve exists.

PMID- 17218185
TI  - The transverse figure-of-eight suture for securing the nail.
AB  - Various techniques have been described for securing the nail plate back in its
      anatomic position after trauma or for reconstructive exposure. The figure-of
      eight suture technique uses the paronychial folds and notches in the distal
      aspect of the nail plate to create both ventral and proximal forces to secure the
      nail plate under the eponychial fold. The transverse figure-of-eight suture
      prevents the nail from moving distally or dorsally. It is simple, secure, and
      easily taught to non-hand surgeons. This technique can also be used when the
      eponychium is damaged. It is a useful adjunct to the armamentarium of anyone
      treating finger-tip injuries.

PMID- 17218186
TI  - Adventitial cyst of the radial artery with a wrist joint connection.

PMID- 17218187
TI  - Preventing alcohol-exposed pregnancies: a randomized controlled trial.
AB  - BACKGROUND: Prenatal alcohol exposure is a leading preventable cause of birth
      defects and developmental disabilities in the United States. DESIGN: A randomized
      controlled trial (2002-2005; data analyzed 2005-2006) of a brief motivational
      intervention to reduce the risk of an alcohol-exposed pregnancy (AEP) in
      preconceptional women by focusing on both risk drinking and ineffective
      contraception use. SETTING/PARTICIPANTS: A total of 830 nonpregnant women, aged
      18-44 years, and currently at risk for an AEP were recruited in six diverse
      settings in Florida, Texas, and Virginia. Combined settings had higher
      proportions of women at risk for AEP (12.5% overall) than in the general
      population (2%). INTERVENTIONS: Participants were randomized to receive
      information plus a brief motivational intervention (n=416) or to receive
      information only (n=414). The brief motivational intervention consisted of four
      counseling sessions and one contraception consultation and services visit. MAIN
      OUTCOME MEASURES: Women consuming more than five drinks on any day or more than
      eight drinks per week on average, were considered risk drinkers; women who had
      intercourse without effective contraception were considered at risk of pregnancy.
      Reversing either or both risk conditions resulted in reduced risk of an AEP.
      RESULTS: Across the follow-up period, the odds ratios (ORs) of being at reduced
      risk for AEP were twofold greater in the intervention group: 3 months, 2.31 (95%
      confidence interval [CI]=1.69-3.20); 6 months, 2.15 (CI=1.52-3.06); 9 months,
      2.11 (CI=1.47-3.03). Between-groups differences by time phase were 18.0%, 17.0%,
      and 14. 8%, respectively. CONCLUSIONS: A brief motivational intervention can
      reduce the risk of an AEP.

PMID- 17218188
TI  - Receipt of preventive services by elders based on composite measures, 1997-2004.
AB  - BACKGROUND: The receipt of routine vaccinations and cancer screening is typically
      tracked separately. Monitoring trends in this way does not measure the overall
      protection conferred by these services on a target population. DESIGN: Telephone
      surveys were conducted in 1997, 2002, and 2004 as part of the Behavioral Risk
      Factor Surveillance System. SETTING/PARTICIPANTS: Randomly selected adults aged
      65 and older from 49 states and Washington DC. MAIN OUTCOME MEASURES:
      Statistically significant changes (p <0.05) in a composite measure of the
      prevalence of U.S. men aged 65 or older who were up to date with recommendations
      for colorectal cancer screening, influenza vaccination, pneumococcal vaccination;
      and for the prevalence of U.S. women aged 65 or older who were up to date for
      these measures as well as for Pap test and screening mammography. RESULTS: The
      percentage of men who reported being up to date on all tests increased from 24.4%
      (1997) to 39.6% (2002) to 41.0% (2004), and the percentage of women increased
      from 18.6% (1997) to 32.4% (2002) to 32.5% (2004). For both groups, results
      varied by education, race/ethnicity, marital status, insurance status, and state,
      as well as whether they had a personal doctor. CONCLUSIONS: Despite increases
      between 1997 and 2004 in the reported receipt of individual cancer screenings and
      vaccinations among U.S. adults aged 65 or older, approximately seven of ten women
      and six of ten men were not up to date on these routine preventive services in
      2004.

PMID- 17218189
TI  - Evaluation of a national physical activity intervention for children: VERB
      campaign, 2002-2004.
AB  - BACKGROUND: Amid concern for the consequences of physical inactivity among
      children, the Centers for Disease Control and Prevention started a campaign using
      commercial marketing methods to promote physical activity to children. DESIGN:
      Longitudinal study using a telephone survey to assess physical activity behaviors
      and attitudes at baseline and for 2 years of follow-up. Relationships of campaign
      awareness to behavioral and psychosocial effects were analyzed with use of
      propensity scoring. PARTICIPANTS: Nationally representative cohort of 2257 parent
      child dyads. INTERVENTION: Marketing campaign (VERB) directed to all U.S.
      children aged 9 to 13 years. Components included general market and ethnic
      specific advertisements on television and radio, in print, and through promotions
      in communities, schools, and on the Internet. Advertising ran nationally at
      consistent levels from June 2002 through June 2004. MAIN OUTCOME MEASURES:
      Psychosocial measures and self-reports of free-time and organized physical
      activity during nonschool hours in the week before the interview and on the day
      before the interview. RESULTS: After 2 years, a dose-response effect was detected
      in the study population. The more children who reported seeing VERB messages, the
      more physical activity they reported and the more positive their attitudes were
      about the benefits of being physically active. Children aware of VERB reported
      engaging in significantly more physical activity than children unaware of VERB.
      These results were considerably stronger than the effects after Year 1, which
      were only for physical activity among subpopulations. CONCLUSIONS: The VERB
      campaign continued to positively influence children's attitudes about physical
      activity and their physical activity behaviors and expanded the effects to more
      children. With adequate and sustained investment, health marketing shows promise
      to affect the attitudes and behavior of children.

PMID- 17218190
TI  - Employer and healthcare policy interventions aimed at adult obesity.
AB  - BACKGROUND: Increasing rates of obesity in the population have made prevention a
      high public health priority. Policy strategies for curtailing obesity have been
      recommended, yet there has been little research on the degree of public support
      for policy-level interventions. METHODS: Participants for this study included
      1139 respondents who were surveyed as part of the Research Triangle Institute
      Obesity Telephone Survey conducted in September 2004. Participants were asked to
      indicate to what degree they favor specific healthcare and work policy strategies
      for treating and preventing adult obesity. Participants were also asked about
      their beliefs regarding the causes of obesity. RESULTS: A majority (85%) favored
      a policy change strategy that offered employers tax breaks if they provided
      adequate exercise facilities in the workplace. Seventy-three percent favored a
      move by healthcare companies to require obesity treatment and prevention. The
      same proportion (72%) favored beneficiary discounts by employers or healthcare
      companies to motivate individuals to maintain or move toward a healthy weight.
      Majorities endorsed a lack of willpower and the cost of healthy food as causes.
      Nearly two thirds did not believe genes or lack of knowledge was related to
      obesity in society, and the sample was split with regard to the belief that
      obesity is caused by society. CONCLUSIONS: The findings suggest that there is
      strong support for healthcare and employment policies in obesity prevention and
      treatment. These findings may be important to policymakers in developing
      population-based strategies to prevent obesity.

PMID- 17218191
TI  - Laboratory screening at preventive health exams: trend of testing, 1978-2004.
AB  - BACKGROUND: Routine laboratory screening at preventive health exams continues to
      be a common practice despite expert opinion dating back to 1979 that supports
      only a few screening tests for apparently healthy adults. This report describes
      trends in such testing over a 27-year period. METHODS: Primary care physicians
      were surveyed five times between 1978 and 2004 at a yearly educational meeting in
      Colorado. Based on case vignettes describing two apparently healthy adults,
      physicians indicated which laboratory tests they would routinely order. RESULTS:
      Of a total of 2364 surveys collected during years 1978, 1983, 1988, 1999, and
      2004, the corresponding percentage of physicians respondents who state they would
      order the following tests for a healthy man aged 35 years were: complete blood
      count (CBC) (87, 75, 73, 49, 46); urinalysis (UA) (93, 86, 79, 52, 44); chemistry
      panel (CHEM) (57, 48, 36, 43, 55); and electrocardiogram (ECG) (37, 27, 24, 9,
      6). For a healthy woman aged 55 years, the corresponding percentages for each
      test were: CBC (89, 89, 86, 64, 67); UA (96, 93, 88, 62, 55); CHEM (70, 70, 66,
      57, 76); ECG (63, 51, 51, 33, 29); and thyroid stimulating hormone (14, 20, 28,
      42, 57). CONCLUSIONS: Although currently practicing physicians continue to report
      that they order screening tests for apparently healthy people, this practice
      appears to have decreased over the past 27 years. This trend may reflect expert
      guidelines and emphasis on medical cost containment.

PMID- 17218192
TI  - Creating a robust public health infrastructure for physical activity promotion.
AB  - The essential role of physical activity both as an independent protective factor
      against numerous common chronic diseases and as a means to maintain a healthy
      weight is gaining increasing scientific recognition. Although the science of
      physical activity promotion is advancing rapidly, the practice of promoting
      physical activity at a population level is in its infancy. The virtual absence of
      a public health practice infrastructure for the promotion of physical activity at
      the local level presents a critical challenge to control policy for chronic
      disease, and particularly obesity. To translate the increasing evidence of the
      value of physical activity into practice will require systemic, multilevel, and
      multisectoral intervention approaches that build individual capability and
      organizational capacity for behavior change, create new social norms, and promote
      policy and environmental changes that support higher levels of energy expenditure
      across the population. This paper highlights societal changes contributing to
      inactivity; describes the evolution and current status of population-based public
      health physical activity promotion efforts in research and practice settings;
      suggests strategies for engaging decision makers, stakeholders, and the general
      public in building the necessary infrastructure to effectively promote physical
      activity; and identifies specific recommendations to spur the creation of a
      robust public health infrastructure for physical activity.

PMID- 17218193
TI  - President's message: resolutions for resolute members.

PMID- 17218194
TI  - It is credible.

PMID- 17218195
TI  - Carotid ultrasound imaging: an effective technique for detecting early
      atherosclerosis-vascular screening for cardiovascular disease has come of age.

PMID- 17218196
TI  - Three-dimensional versus two-dimensional transesophageal echocardiography in
      mitral valve repair.
AB  - OBJECTIVES: We sought to compare the diagnostic performance of 3-dimensional (3D)
      versus 2-dimensional (2D) echocardiography in patients with regurgitant mitral
      valve. BACKGROUND: An accurate assessment of morphology and function of the
      mitral valve is essential for surgical repair. Two-dimensional echocardiography
      has certain spatial limitations that could be overcome by 3D imaging. METHODS:
      Preoperative transesophageal 2D and 3D studies were compared with surgical
      findings in patients undergoing surgical repair for severe mitral regurgitation.
      RESULTS: A total of 81 consecutive patients underwent surgical repair (2002
      2004). There was a high concordance (88%-100%) between both 2D and 3D studies and
      surgical findings in classification of involved segments. 3D imaging more
      accurately classified A1 segment defects (P = .05) and commissural dysfunction (P
      = .02). The 2D study incorrectly classified 22 segments, mainly corresponding to
      complex disease. The 3D study incorrectly classified 14 segments, unrelated to
      complex disease. Good agreement (94%, kappa 0.845) was found between non-expert
      and expert interpretations of 3D images. CONCLUSIONS: Three-dimensional
      echocardiography offers high accuracy in mitral valve evaluation. It may
      complement 2D study in patients with complex valve anatomy, where surgical
      decisions are more difficult. The images can be easily interpreted by
      professionals without a high degree of experience.

PMID- 17218197
TI  - Quantitative real-time 3-dimensional stress echocardiography: a preliminary
      investigation of feasibility and effectiveness.
AB  - BACKGROUND: Use of rapidly emerging real-time 3-dimensional (3D) echocardiography
      promises to improve the diagnostic accuracy of stress echocardiography (SE).
      However, widespread acceptance of 3D-SE, based on real-time 3D echocardiography,
      is hampered in part by lack of efficient, accurate, and objective analysis tools.
      METHODS: We propose novel algorithms for interactive visualization, registration
      (alignment), and quantitative analysis of prestress and poststress real-time 3D
      echocardiography to facilitate an objective diagnosis. In a preliminary
      evaluation, two experts independently performed wall-motion analysis in 15
      patients with known/suspected coronary artery disease, using the novel
      quantitative 3D-SE methods. RESULTS: Compared with previously reported values for
      conventional 2-dimensional SE, improved interexpert agreement (kappa = 0.85) was
      observed for segment-wise classification of normal/abnormal wall motion using the
      novel 3D-SE methods. Overall, 6 of 6 patients with abnormal myocardial segments
      were correctly identified by both experts with 3D-SE, compared with 4 of 6 with
      conventional 2-dimensional SE. CONCLUSION: Initial results are promising and
      indicate the feasibility and potential of our proposed quantitative 3D-SE
      methodologies for improving diagnosis of wall-motion abnormalities.

PMID- 17218199
TI  - Advanced quantitative echocardiography in arrhythmogenic right ventricular
      cardiomyopathy.
AB  - BACKGROUND: Arrhythmogenic right ventricular (RV) cardiomyopathy (ARVC) is a
      regional disease of the RV myocardium with variable degrees of left ventricular
      involvement. Three-dimensional echocardiography and Doppler tissue imaging (DTI)
      are new echocardiographic modalities for the evaluation of global and regional
      function, but the diagnostic potential remains to be assessed. METHODS: Twenty
      patients with previously established ARVC were evaluated by 3-dimensional
      echocardiography and DTI, and compared with 32 age- and sex-matched control
      subjects. RESULTS: Using 3-dimensional echocardiography, patients with ARVC had a
      decreased RV ejection fraction (0.47 +/- 0.08 vs 0.53 +/- 0.05, P < .01), and a
      decreased peak lateral systolic annular velocity by pulsed wave imaging of both
      the RV (11.9 +/- 2.6 vs 15.1 +/- 3.7 cm/s, P < .01) and the left ventricle (7.0
      +/- 2.6 vs 9.5 +/- 1.9 cm/s, P < .01). DTI showed decreased regional systolic
      strain, but with wide variation in the measurements. CONCLUSION: Three
      dimensional echocardiography identifies decreased RV ejection fraction in ARVC.
      Assessment of regional contractility by DTI is limited by wide variation.
      Echocardiographic evaluation of the longitudinal motility appears to be a
      sensitive marker of preclinical left ventricular involvement.

PMID- 17218198
TI  - B-type natriuretic peptide is not a marker of ischemia during dobutamine stress
      echocardiography.
AB  - Elevated levels of B-type natriuretic peptide (BNP) have been reported in
      association with exercise-induced ischemia. Data regarding BNP as a marker of
      ischemia during dobutamine stress echocardiography (DSE) are not conclusive. This
      study was designed to evaluate changes in BNP during DSE. A total of 74 patients
      referred to rule out ischemia by DSE were enrolled in the study. All patients had
      DSE using standard protocol. Of 74 patients enrolled, 6 were excluded because of
      nondiagnostic tests. Of the remaining 68 patients, 15 had positive DSE and 53
      were negative for ischemia. The BNP levels (mean +/- SD) in the patients without
      ischemia were 42.5 pg/mL (+/-SD 47.6) at baseline and 41.9 pg/mL (+/-SD 48.9) at
      peak, and the measurements in the patients with ischemia were 90 pg/mL (+/-SD
      171.7) at baseline and 88 pg/mL (+/-SD 149.2) at peak. BNP levels do not change
      during DSE with or without evidence of ischemia.

PMID- 17218200
TI  - The assessment of left ventricular twist in anterior wall myocardial infarction
      using two-dimensional speckle tracking imaging.
AB  - BACKGROUND: Two-dimensional speckle tracking imaging allows noninvasive
      measurement of left ventricular (LV) strain, rotation, and displacement. We
      investigated whether LV twist would be depressed in anterior wall myocardial
      infarction (MI) as a result of reduced apical rotation. METHODS: Basal and apical
      LV short-axis images were acquired in 30 patients with anterior wall MI. Using
      commercially available 2-dimensional strain software, time domain speckle
      tracking was performed, and regional LV strain, rotation, and radial displacement
      were obtained in each plane. LV twist was defined as apical LV rotation relative
      to the base. Patients were divided into two groups according to global LV
      systolic function (normal LV ejection fraction [LVEF] group [LVEF > or = 45%, n =
      16] and abnormal LVEF group [LVEF < 45%, n = 14]). RESULTS: Circumferential
      strain in the apex was significantly reduced in abnormal LVEF group compared with
      normal LVEF group (-7.3 +/- 2.6 vs -13.5 +/- 4.1, P < .001). Peak LV twist was
      significantly reduced in abnormal LVEF group (5.6 +/- 2.6 vs 9.8 +/- 4.0 degrees,
      P < .005) mainly because of reduced apical rotation. Peak positive and negative
      twist velocity was also significantly depressed (38.8 +/- 11.3 vs 52.1 +/- 19.3
      degree/s, P < .05, and -42.6 +/- 17.8 vs -63.4 +/- 28.0 degree/s, P < .05,
      respectively). Significant correlation was noted between peak twist and LVEF (r =
      0.73, P < .001) and LV end-systolic volume (r = 0.56, P < .001). The twist
      displacement loop was markedly distorted in abnormal LVEF group. CONCLUSIONS:
      Systolic twist was decreased and diastolic untwisting was depressed in accordance
      with LV systolic dysfunction in anterior wall MI. These results suggest the
      significant impact of global LV systolic function on LV twist and twist
      displacement loops in patients with anterior wall MI.

PMID- 17218201
TI  - Assessment of left ventricular rotation and torsion with two-dimensional speckle
      tracking echocardiography.
AB  - BACKGROUND: Speckle tracking echocardiography (STE) has a unique feature of angle
      independence and, thus, may provide a powerful means of assessing left
      ventricular (LV) torsion (LVtor). The aims of this study were to assess: (1) the
      feasibility of 2-dimensional STE in the measurement of LVtor; and (2) the
      relationship of LVtor with age and conventional echocardiographic parameters.
      METHODS: We consecutively recruited 160 healthy volunteers. After obtaining
      conventional echocardiographic parameters, apical and basal short-axis rotations
      were assessed with STE. LVtor was defined as the net difference between rotation
      angles in the two short-axis planes normalized for LV longitudinal length.
      RESULTS: Reliable LVtor measurement was possible only in 56 volunteers (35%).
      This low feasibility was largely a result of the failure to obtain reliable basal
      rotation values. In 56 volunteers who were finally enrolled in this study, a
      significant correlation was found between LV ejection fraction and LVtor (r =
      0.56, P < .001) and this correlation was attributed to apical (r = 0.47, P <
      .001) but not basal (P = .14) rotation. There was no significant change in LVtor
      with aging. However, initial counterclockwise motion (r = -0.51, P = .001) and
      its interval (r = -0.44, P = .001) in the basal rotation gradually decreased with
      aging, and correlated with early transmitral inflow velocity (r = 0.44 and 0.49,
      respectively) and its deceleration time (r = -0.43 and -0.48, respectively) (all
      P < .001). In contrast, such correlations were not found for initial clockwise
      motion and its interval in the apical rotation. CONCLUSIONS: Currently, STE has
      limited feasibility in the measurement of LVtor. There was no significant age
      related change in LVtor. In LV rotations, basal rotation was affected by the age
      related changes in the LV early diastolic filling, whereas apical rotation was
      mainly related to LV systolic performance.

PMID- 17218202
TI  - Mechanisms of reduction of mitral regurgitation by cardiac resynchronization
      therapy.
AB  - OBJECTIVES: We sought to investigate the effects of improved left ventricular
      (LV) synchrony on secondary mitral regurgitation in patients receiving cardiac
      resynchronization therapy for severe heart failure. METHODS: A total of 22
      patients, aged 63 +/- 8 years, were studied during sinus rhythm (unpaced), during
      LV pacing, and during biventricular pacing. Echocardiography was used to assess
      LV shape, mitral valve morphology and function, and global systolic and diastolic
      function. Mechanical ventricular synchrony was calculated from regional systolic
      timings and velocities, using tissue Doppler. RESULTS: Synchronicity index of LV
      longitudinal function improved from 36 +/- 19 to 14 +/- 8 milliseconds with LV
      pacing, and from 31 +/- 17 to 12 +/- 7 milliseconds with biventricular pacing
      (both P < .01). Heterogeneity of myocardial velocities decreased and mean
      systolic longitudinal velocity increased. Long-axis and short-axis systolic
      dimensions decreased, and the LV became less spherical. Apical displacement of
      coaptation from the plane of the mitral annulus, and annular diameter, were
      reduced. The severity of mitral regurgitation decreased: vena contracta diameter
      decreased from 5.3 +/- 1.7 to 4.1 +/- 1.5 mm with LV pacing, and from 5.2 +/- 1.7
      to 4.0 +/- 1.7 mm with biventricular pacing (both P < .05), correlating with the
      increase in mean systolic longitudinal velocity (r = -0.49 for LV pacing and r = 
      0.67 for biventricular pacing, both P < .05). CONCLUSIONS: Cardiac
      resynchronization reduces mitral regurgitation by improving LV mechanical
      synchrony, which leads to an increase in LV longitudinal function and a reduction
      in subvalvar traction.

PMID- 17218203
TI  - Role of diastolic dyssynchrony in the delayed relaxation pattern of left
      ventricular filling.
AB  - We investigated the extent to which diastolic dyssynchrony contributes to the
      delayed relaxation pattern of left ventricular filling and limitation in exercise
      capacity. In 100 patients with diabetes, preserved left ventricular systolic
      function, normal filling pressure, and no coronary disease, we measured magnitude
      of early diastolic tissue lengthening (tissue velocity and strain rate) and
      diastolic dyssynchrony (SD in QRS to peak early diastolic tissue velocity
      interval across 4 basal myocardial segments). From transmitral flow patients were
      divided into those with normal filling (50 patients) and delayed relaxation (50
      patients). Myocardial lengthening was reduced and SD in interval from QRS onset
      to peak early diastolic tissue velocity across all segments was higher in
      patients with delayed relaxation compared with control patients. Myocardial
      lengthening was the only predictor of delayed relaxation and correlation with
      exercise capacity was better for lengthening indices than SD in interval from QRS
      onset to peak early diastolic tissue velocity across all segments. Therefore, in
      this group a reduced rate of myocardial lengthening plays a more important role
      in delayed relaxation than diastolic dyssynchrony.

PMID- 17218204
TI  - Cardiac resynchronization therapy and the emerging role of echocardiography (part
      1): indications and results from current studies.
AB  - Cardiac resynchronization therapy (CRT) has been established as an adjunctive
      treatment for patients with left ventricular systolic dysfunction and medically
      refractory heart failure with a wide QRS interval. Echocardiography can be used
      to determine the response in left ventricular structure and function after device
      implantation and emerging evidence as a method for selection of patients who may
      derive clinical benefit from CRT. This review discusses the applications of CRT,
      including results of clinical trials and the current experience using
      echocardiography. Part 2 will address the practical aspects of obtaining
      echocardiographic data in patients who are potential candidates for CRT and
      optimization of pacemaker settings after device implantation.

PMID- 17218205
TI  - Cardiac resynchronization therapy and the emerging role of echocardiography (part
      2): the comprehensive examination.
AB  - Cardiac resynchronization therapy has been established as an adjunctive treatment
      for patients with severe left ventricular systolic dysfunction and medically
      refractory heart failure symptoms with a prolonged electrocardiographic QRS
      interval. Echocardiography has emerged as a useful method to evaluate patients
      who are considered for cardiac resynchronization therapy. This review outlines
      measurements of ventricular performance to be used in this patient population
      including echocardiographic optimization of cardiac resynchronization therapy
      device settings.

PMID- 17218206
TI  - The role of echocardiography in the assessment of mechanical dyssynchrony and its
      importance in predicting response to prognosis after cardiac resynchronization
      therapy.
AB  - The aim of this review is to synthesize the published evidence regarding the
      benefits of identifying mechanical asynchrony before implantation of
      biventricular devices, and the role of echocardiography in the identification and
      quantification of mechanical asynchrony. It summarizes the published studies
      addressing the several echocardiographic parameters of dyssynchrony that have
      already proven to predict response to cardiac resynchronization therapy. M-mode
      echocardiography, Doppler tissue imaging, strain and strain rate imaging, tissue
      tracking, and 3-dimensional echocardiography parameters of dyssynchrony shown to
      be able to identify responders are discussed. In addition, the prognostic
      implication of the identification of mechanical asynchrony before implantation is
      addressed. A summary of the published evidence of the echocardiographic
      parameters able to identify patients more likely to derive a prognostic benefit
      is provided. Finally, it mentions some of the current uncertainties and possible
      future applications of echocardiographic evaluation of dyssynchrony.

PMID- 17218207
TI  - Left ventricular dynamic obstruction by atypical papillary muscle morphology: is
      this finding so unusual in clinical practice?

PMID- 17218208
TI  - The changing spectrum of porcine bioprosthetic valve failure.

PMID- 17218209
TI  - A 10-year comparison of explanted Hancock-II and Carpentier-Edwards supraannular
      bioprostheses.
AB  - BACKGROUND: Bioprosthetic heart valves are more frequently being used in valve
      replacement procedures today. Although second-generation bioprosthetic valves
      have improved functionality over their first-generation counterparts, they still
      often fail due to primary tissue degeneration. METHODS: This study examines two
      second-generation porcine valves after surgical explantation, the Hancock-II
      (HAN; Medtronic Heart Valve Division, Irvine, CA, USA) and the Carpentier-Edwards
      supraannular (CE-SAV; Baxter Healthcare Corporation, now Edwards LifeSciences,
      Irvine, CA, USA), with special attention to morphological/histological changes
      and reasons for valve failure. A total of 98 HAN and 65 CE-SAV valves were
      explanted and seen over a 10-year period. RESULTS: CE-SAV valves had a longer
      average implant duration than HAN valves (13.9+/-3.9 years vs. 10.0+/-5.1 years).
      Compared with HAN valves, CE-SAV valves also had a higher incidence of stent
      deformation (41.5% vs. 14.3%), calcification (75.4% vs. 54.1%), and pannus (100%
      vs. 91.8%). CONCLUSIONS: The greater degenerative changes seen with CE-SAV valves
      over HAN valves may be due to the longer implant duration of CE-SAV valves in
      this series. To our knowledge, the present study is the first direct
      morphological comparison of these two valve models.

PMID- 17218210
TI  - C-reactive protein: a nontraditional serum marker of cardiovascular risk.
AB  - Cardiovascular disease (CVD) is multifactorial in etiology. Traditional
      cardiovascular risk factors, such as increased cholesterol concentrations and
      blood pressure, are used to assess CVD risk. Recently, better understanding of
      the role of inflammation in atherosclerosis has prompted many to propose the
      measurement of various inflammatory markers to better identify those who are at
      increased risk. C-reactive protein (CRP) is found in endothelial atherosclerotic
      lesions, and evidence suggests that it may play a role in atherogenesis. Of
      candidate serum markers that might add information to clinical risk assessment,
      high-sensitivity C-reactive protein (hsCRP) measurement has the most potential
      for clinical use for multiple reasons: (a) high hsCRP is associated with a
      twofold to a threefold increase in the prevalence of myocardial infarction,
      stroke, and peripheral vascular disease, and it predicts incident cardiovascular
      events in those with and without preexisting CVD; (b) the increased risk
      associated with high hsCRP is independent of other established risk factors; (c)
      hsCRP augments the predictive capacity of the Framingham Risk Score; (d) hsCRP
      assays are standardized, and this analyte is biologically stable over time; (e)
      various risk-reducing interventions also reduce hsCRP, and research is underway
      to assess whether specifically targeting hsCRP reduces CVD risk. National
      guidelines regarding the clinical utility of hsCRP in primary and secondary
      prevention settings have been recently issued.

PMID- 17218211
TI  - Heart tumors in children and adults: clinicopathological study of 59 patients
      from a surgical center.
AB  - BACKGROUND: Heart tumors are rare lesions with variegated histological types.
      Their clinicopathological features could be more comprehensively categorized.
      METHODS: This is a 19-year retrospective study of 17 infants/toddlers (<2 years
      of age) and 42 patients aged between 14 and 79 years (mean = 51.5) in a surgical
      center. RESULTS: Congenital tumors (n = 17; 29%), including rhabdomyomas (n = 9),
      ventricular fibromas (n = 6), and hemangiomas (n = 1), required surgery mainly
      because of mass effect. Familial myofibromatosis was the only embolic congenital
      lesion. Acquired benign tumors (n = 28; 47%) included myxomas (n = 21),
      fibroelastomas (n = 3), myofibroblastic inflammatory tumors (n = 2), and lipomas
      (n = 2). Eight (29%) were revealed by systemic embolization. These benign
      noncongenital tumors were all treated by complete resection, except for an
      incompletely resected lipoma of the mitral valve. Postoperative arrhythmia (n =
      1) and pericardial effusion (n = 3) were the only complications. Primary sarcomas
      (n = 8; 14%) were mostly vascular tumors (five of eight), and patients with high
      grade tumors had a mean survival of 15 months (n = 5). Cardiac metastases (n = 6;
      10%) were from carcinomas (n = 3) or sarcomas (n = 3); apart from a necrotic
      metastasis, all patients died (mean survival of 6 months). CONCLUSIONS: This
      study shows that, regardless of patients' age, heart tumors can be classified as:
      (a) congenital lesions, which are spontaneously nonprogressive or regressive
      lesions possibly requiring surgery mainly because of mass effect; (b) acquired
      benign tumors, which are lesions requiring surgery often because of embolization
      risk; and (c) primary and secondary malignant tumors, which are lesions with
      globally poor prognosis but with some indications for resection.

PMID- 17218212
TI  - Toward cell therapy for vascular calcification: osteoclast-mediated
      demineralization of calcified elastin.
AB  - BACKGROUND: Elastin-oriented vascular calcification is a clinically significant
      feature, which involves formation of ectopic bone-like structures. Taking
      advantage of the similarities between arterial calcification and bone regulation,
      our hypothesis was that therapeutic approaches for limitation of vascular
      calcification could be developed using site-specific delivery of autologous
      osteoclasts. In the present paper, we tested the hypothesis that bone-marrow
      derived osteoclasts have the ability to demineralize calcified elastin, without
      significant alterations in elastin integrity. METHODS: Active, multinucleated
      osteoclasts were obtained by in vitro maturation of rat bone-marrow-derived
      progenitor cells in the presence of vitamin D(3) and retinoic acid. Cell
      phenotype was validated by staining for tartrate-resistant acid phosphatase,
      formation of resorption pits on hydroxyapatite-coated disks, and RT-PCR for
      identification of cathepsin K gene expression. Calcified aortic elastin was
      seeded with osteoclasts and calcium, and phosphorous levels were monitored in
      gels and culture media to detect demineralization of elastin. Soluble elastin
      peptides were also monitored in culture media for elastin degradation. For in
      vivo experiments, pure aortic elastin was coimplanted with allogenic osteoclasts
      subdermally into rats, and the degree of elastin calcification and degradation
      was evaluated using mineral analysis and desmosine quantitation. RESULTS: Bone
      marrow-derived osteoclasts reduced mineral content of calcified elastin in vitro
      by 80%. Moreover, in vivo implantation of allogenic osteoclasts in the vicinity
      of calcifying elastin limited elastin mineralization by almost 50%, in the
      absence of detectable elastin degradation. CONCLUSIONS: Osteoclasts have the
      ability to demineralize calcified elastin, without significant alterations in
      elastin integrity.

PMID- 17218213
TI  - Histologic findings proving the existence of humoral rejection in a cardiac
      allograft.
AB  - Humoral rejection (HR) of the cardiac allograft is neither well characterized nor
      universally recognized in the transplant/pathology-related literature. One reason
      for this is that the histologic light-microscopic features are inconsistent,
      making HR difficult to recognize in the majority of cases. We report an unusual
      case of cardiac allograft rejection in a patient with a complicated postoperative
      course who ultimately died within 6 months of transplant. Premortem, HR was not
      diagnosed in multiple cardiac biopsies. The autopsy revealed unequivocal
      histologic and immunohistochemical evidence of HR. Vascular distension and
      endocardial infiltration by numerous macrophages were noted only in the cardiac
      allograft and were notably absent in the native tissue present within the
      anastomotic sites. There was capillary deposition of immunoglobulin and
      complement shown by immunofluorescence staining of frozen tissue, and there was
      diffuse immunohistochemical staining for C4d within the intramyocardial vessels.
      This case appears to represent an exaggerated antibody-mediated rejection of the
      cardiac allograft.

PMID- 17218214
TI  - Stereology: a simplified and more time-efficient method than planimetry for the
      quantitative analysis of vascular structures in different models of intimal
      thickening.
AB  - OBJECTIVE: Semiautomatic computer-assisted planimetry is currently the standard
      morphometric technique in models of intimal thickening. We evaluated
      stereological point counting as an alternative method for the measurement of
      cross-sectional vascular areas (lumen, intima, and media) by comparing precision,
      efficiency, and variance components. METHODS: Sections from murine
      atherosclerotic aorta (n = 21), stented rabbit iliac arteries (n = 30), and
      porcine coronary arteries (n = 30) were analyzed at two institutes using both
      techniques. To determine reproducibility, porcine arteries were measured twice.
      RESULTS: Area measurements showed almost identical means and standard deviations
      for planimetry and stereology [e.g., intima (mm2): 0.10+/-0.11 vs. 0.12+/-0.12
      (mouse), 0.60+/-0.16 vs. 0.60+/-0.15 (rabbit), and 1.92+/-1.52 vs. 1.97+/-1.61
      (pig)]. Deming regression and Bland-Altman plots demonstrated a good agreement
      between both techniques that was not influenced by artery size. Both methods
      exhibited excellent repeatability, although planimetry (-0.18+/-0.27) was more
      precise than stereology (-0.17+/-0.47; variance, P < .01, Levene test). In
      addition, intraoperator variance (error inherent to the technique) was greater
      for stereology (1.6-15.8% vs. 4.8-33.5%), whereas interoperator variance (error
      between institutes) was very small for both methods (0.1-0.9% vs. 0.1-1.7%).
      Indeed, biologic variability was, by far, the most important variance component
      in all measurements (84-98% vs. 65-95%). Finally, stereology required 20% (mouse;
      P < .05) to 40% (pig; P < .001) less time to complete analysis. CONCLUSION: The
      quantification of vascular structures by planimetry and stereology yielded
      comparable results in all models of intimal thickening, but stereology proved to
      be less time-consuming. Therefore, study design may dictate the most appropriate
      choice of technique.

PMID- 17218215
TI  - Irreversible intrapulmonary vascular changes after pulmonary vein stenosis
      complicating catheter ablation for atrial fibrillation.
AB  - BACKGROUND: Pulmonary vein stenosis is a recognized complication of catheter
      ablation of arrhythmias emanating from the pulmonary vein; however, there is
      little information on secondary effects of pulmonary vein stenosis on lung
      tissue. METHODS AND RESULTS: A 55-year-old man with a history of paroxysmal
      atrial fibrillation refractory to antiarrhythmic medication had radiofrequency
      ablation in April 2003 and July 2003. Although these procedures were successful
      in resolving the patient's arrhythmia, they were complicated by the development
      of pulmonary vein stenosis of all four veins and pulmonary hypertension requiring
      patch annuloplasty of the pulmonary veins in October 2003. The patient was
      referred to our center for pulmonary vein stent placement in December 2003, June
      2004, and August 2004, each time for recurrent hemoptysis. Due to persistent
      hemoptysis over the next several months, the patient underwent left lower lung
      lobectomy in September 2005. Microscopic examination of the lung showed marked
      medial thickening and intimal hyperplasia of large and small pulmonary veins and
      arteries, as well as focal organizing thrombi in the small arteries. The lung
      tissue showed extensive hemosiderin deposition indicative of prior hemorrhage.
      CONCLUSION: Chronic pulmonary vein stenosis after radiofrequency ablation of
      atrial fibrillation results in irreversible venous and arterial morphologic
      changes throughout the lung, including areas both close to, and remote from, the
      site of catheter ablation. Because there are persistent pathological changes
      remote from the ablation site causing the pulmonary hypertension, stenting the
      site of ablation to reopen large pulmonary veins may not be effective in treating
      the pulmonary hypertension.

PMID- 17218216
TI  - Malignant small round cell tumor of the heart: a diagnostic dilemma.
AB  - We report a rare malignant small round cell tumor of the heart in a 26-year-old
      woman. She had been symptomatic 15 days after vaginal delivery.
      Immunohistochemistry revealed divergent differentiation; hence, the tumor was
      designated as desmoplastic small round cell tumor. This is the first report of
      such a tumor in the heart.

PMID- 17218217
TI  - Papillary fibroelastoma of the aortic valve: incidental finding with
      intraoperative transesophageal echocardiography.
AB  - Papillary fibroelastoma is a benign but rare tumor of the heart, usually derived
      from the endocardium. Although rarely clinically symptomatic, fibroelastoma has a
      potential for valvular dysfunction and systemic embolization. In this article, we
      show the images of a previously undiagnosed mass that was surgically excised in a
      73-year-old woman.

PMID- 17218218
TI  - Postmortem examination of the CorCap device: macroscopic and microscopic
      findings.

PMID- 17218219
TI  - Parasitic myoma under the diaphragm.

PMID- 17218220
TI  - A multidisciplinary approach to the diagnosis and management of chronic pain
      associated with pelvic venous incompetence.

PMID- 17218221
TI  - Pathologist-clinician communication: the role of the pathologist as consultant to
      the minimally invasive gynecologic surgeon.

PMID- 17218222
TI  - Abnormal uterine bleeding: imaging techniques for evaluation of the uterine
      cavity and endometrium before minimally invasive surgery--the case for
      transvaginal ultrasonography.
AB  - Transvaginal ultrasound has been utilized for first line evaluation of abnormal
      uterine bleeding since its development in the early 1980's. The benefits and
      diagnostic effectiveness of transvaginal ultrasound in assessing the uterus,
      unlike hysteroscopy, extends to the complete pelvis. The ease of application,
      patient acceptance, and immediacy of results are rapidly apparent. Comparisons
      with hysteroscopic evaluation are discussed. While tissue diagnosis is still the
      gold standard, transvaginal sonography lets one know what surgical procedure to
      plan for from hysteroscopy to Endoscopy or laparotomy, including when no further
      surgical evaluation is necessary.

PMID- 17218223
TI  - In the management of abnormal uterine bleeding, is office hysteroscopy preferable
      to sonography? The case for hysteroscopy.
AB  - Office hysteroscopy for the diagnosis and management of abnormal uterine bleeding
      has developed into an easily performed procedure, with minimal discomfort and
      significantly reduced risks and expense. Miniaturization of instruments and safer
      liquid distention media, along with effective local analgesia, have made the
      procedure a fast, effective, and much more precise way to detect intrauterine
      abnormalities, as well as to better define the correct plan for any proposed
      operative management. In addition to the above, hysteroscopy is considered the
      "gold standard" for evaluating the uterine cavity. Numerous studies comparing
      hysteroscopy to sonography, with or without saline solution infusion are cited,
      along with other studies comparing hysteroscopy to blind biopsy and curettage,
      all indicating that hysteroscopy is more accurate, with fewer false-positive and
      false-negative results.

PMID- 17218224
TI  - Surgical adhesions: a timely update, a great challenge for the future.
AB  - Damage to the peritoneum during abdominal surgery triggers a cascade of events
      aimed at repairing the damage. As part of this process, fibrin is deposited,
      which is the precursor to the formation of an adhesion between 2 damaged
      peritoneal surfaces. This can have a significant impact on morbidity and even
      mortality as well as large cost implications. Strategies to reduce adhesion
      formation include improving surgical techniques, optimizing laparoscopy
      conditions, using pharmacologic interventions targeted at the inflammatory
      response and/or fibrin deposition, and using agents that provide a physical
      barrier to adhesion formation. While these strategies have provided some success,
      none have yet proved totally successful in abolishing adhesions. Further research
      to ensure that adhesion prevention is optimal is therefore essential.

PMID- 17218225
TI  - Villar's nodule: a case report and systematic literature review of endometriosis
      externa of the umbilicus.
AB  - We report a case of umbilical endometriosis externa and systematically review the
      literature regarding this finding. In our case report, a 47-year-old woman with
      cyclic umbilical bleeding, pelvic pain, and no previous umbilical surgery
      developed a spontaneous umbilical endometrioma, cured by surgical resection and
      bilateral salpingo-oophorectomy. In our review, 122 patients with documented
      umbilical endometriomas from 1966 to the present and 109 cases reported before
      1953 were analyzed. Procedures used for diagnosis and/or therapeutic intervention
      included umbilical biopsy or resection, abdominal wall repair, diagnostic and/or
      operative laparoscopy, adhesiolysis, hysterectomy, and bilateral salpingo
      oophorectomy. Variables included patient age; race; medical and surgical history;
      past use of oral contraceptives; history of umbilical pain, bleeding, or
      swelling; duration of signs and symptoms; size and color of the lesion;
      diagnostic evaluations; and medical or surgical management. Mean age of the study
      population was 37.7 +/- 0.98 years. Up to 40% of patients with extrapelvic
      endometriosis present with umbilical endometriomas, with symptoms occurring an
      average of 17.8 +/- 3.9 months before presentation. Lesions averaged 2.3 +/- 0.2
      cm in diameter; were predominantly brown (19.1%), blue (13.2%), or purple
      (10.3%); and patients frequently had with pain (77.93%), cyclical bleeding
      (47.1%), and swelling (88.2%). Most patients had no history of endometriosis
      (73.1%), and laparoscopic, umbilical trocar-related seeding was identified in
      only 5 patients. Three patients received medical management, and surgical
      management was invariably curative, though 1 patient required repeat surgical
      therapy. Umbilical endometriosis is a common manifestation of external
      endometriosis, representing primary or secondary endometriosis, with a typical
      presentation that has little variation. Laparoscopic endometrioid tissue excision
      can result in iatrogenic seeding to the umbilicus. Historical and physical
      findings are pathognomonic, thus justifying a formal name--Villar's nodule, after
      the initial reporting physician. Surgical intervention is recommended, but
      medical therapy may result in long-term symptom control with minimal malignancy
      risk.

PMID- 17218226
TI  - Outcome after rectum or sigmoid resection: a review for gynecologists.
AB  - It remains unclear when to perform a discoid or segmental bowel resection for
      large endometriotic nodules with intestinal invasion. Moreover, endometriosis
      series are rather small to fully evaluate functional consequences of bowel
      resection. We therefore reviewed the incidence of leakage and functional problems
      after anterior and sigmoid resection as reported in the surgical literature
      albeit for other indications. Endoscopic resection clearly is feasible but
      requires an experienced surgeon. The incidence of leakage is not different after
      hand-sewn or stapled anastomosis, but is higher after a low rectum resection than
      after a sigmoid resection. Similarly, functional bowel problems are higher after
      a low rectum resection than after sigmoid resection. Low rectum resection in
      addition can be associated with functional bladder problems and sexual
      disturbances as anorgasmia. In conclusion, short- and long-term complications are
      much higher after a low rectum than after a sigmoid resection. This seems to be
      important in making the decision to perform a discoid or a segmental bowel
      resection for severe endometriosis.

PMID- 17218227
TI  - Comparison of the long-term histopathologic and morphologic changes after
      endometrial rollerball ablation and resection: a prospective randomized trial.
AB  - STUDY OBJECTIVE: To compare long-term histologic features of endometrial
      rollerball ablation versus resection. DESIGN: Randomized clinical trial (Canadian
      Task Force classification I). SETTING: Akdeniz University School of Medicine.
      PATIENTS: Women with menorrhagia undergoing endometrial ablation. INTERVENTION:
      Comparison of patients with menorrhagia undergoing endometrial resection and
      ablation. MEASUREMENTS AND MAIN RESULTS: Endometrial rollerball ablation (n = 23
      women) and resection (n = 25) were followed by second-look office hysteroscopy
      with endometrial biopsy. Mean follow-up to second look hysteroscopy after
      rollerball ablation and loop resection was 33.4 +/- 2.1 and 31.1 +/- 2.6 months,
      respectively. Complete atrophy and partial adhesion or obliteration of the cavity
      and fibrosis were observed at second-look hysteroscopy and were similar in both
      groups. Whereas all random biopsy specimens after both ablation and resection
      revealed diminished endometrial glands with varied necrosis and scarring, the
      number of endometrial glands per field was not correlated with amount of bleeding
      or menstrual pattern. Bleeding patterns were similar between the groups. No
      precancerous or malignant lesion was found after the procedures. CONCLUSION:
      Although efficacy of both endometrial ablation and resection is related to
      initial thermal destruction and correlated with postablation hysteroscopic and
      histologic findings, endometrial regrowth may be expected and is not a failure of
      ablation. Both procedures revealed histopathologically and clinically similar
      results.

PMID- 17218228
TI  - Laparoscopy in the evaluation of women with unexplained ascites: an invaluable
      diagnostic tool.
AB  - STUDY OBJECTIVE: To assess whether laparoscopy is a reliable technique for the
      investigation of women presenting with ascites and in whom the diagnosis remains
      obscure. DESIGN: Prospective nonrandomized clinical study (Canadian Task Force
      classification II-2). SETTING: University Departments of a tertiary referral
      center. PATIENTS: Women presenting in our institution with ascites in whom the
      diagnosis remained obscure after an extensive nonoperative diagnostic work-up.
      INTERVENTION: Undiagnosed cases were submitted to laparoscopy, and selective
      biopsy specimens were taken for histologic study. MEASUREMENTS AND MAIN RESULTS:
      Over a 3-year period, 73 patients were admitted to our institution with diffuse
      ascites. In 9 patients (12.3%), the diagnosis remained obscure, and these
      patients were further investigated with laparoscopy. Selective biopsy specimens
      obtained at laparoscopy clarified the specific cause of the ascites in all 9
      patients. Peritoneal carcinomatosis was responsible in 5 patients (a metastatic
      gastrointestinal tumor in 1 patient, a malignant mesothelioma of the peritoneum
      in 1 patient, and a serous papillary carcinoma of the peritoneum and of the ovary
      in 2 and 1 patients, respectively). Three patients were found with miliary
      peritoneal tuberculosis, and the last patient had an unusual peritoneal reaction
      to methylene blue after laparoscopic adhesiolysis. CONCLUSION: Laparoscopy is a
      valuable means of assessing the peritoneal cavity in patients with unexplained
      ascites, where the primary cause remains unclear. The diagnosis can be accurately
      made with selective biopsy specimens, and appropriate treatment can be instituted
      without delay.

PMID- 17218229
TI  - The prevalence of fimbrial pathology in patients with early stages of
      endometriosis.
AB  - STUDY OBJECTIVE: The presence of fimbrial pathology in advanced endometriosis is
      clearly understood. However, little is known about the prevalence of fimbrial
      pathology in early stages of endometriosis. The purpose of this study is to
      determine the prevalence of fimbrial pathology in patients with infertility with
      early stages of endometriosis. DESIGN: Historical cohort study (Canadian Task
      Force classification II/III). SETTING: Tertiary referral center. PATIENTS: The
      study group (Group 1) consisted of 315 infertile women who were found to have
      stage I or stage II endometriosis, and the control group (Group 2) consisted of
      152 infertile women without endometriosis (Group 2). INTERVENTION: Laparoscopic
      evaluation for the presence and type of fimbrial pathology. MEASUREMENTS AND MAIN
      RESULTS: The prevalence of fimbrial pathology was significantly higher in
      infertile patients with early stages of endometriosis (50.2%) compared with
      infertile patients with no endometriosis (17.8%, p <.0001). CONCLUSION: These
      preliminary data suggest the presence of fimbrial pathology in many patients with
      early stages of endometriosis. Such pathology may act as a mechanical factor
      interfering with the ovum pick-up mechanism.

PMID- 17218230
TI  - Pentoxifylline therapy after laparoscopic surgery for different stages of
      endometriosis: a prospective, double-blind, randomized, placebo-controlled study.
AB  - STUDY OBJECTIVE: To evaluate the effects of pentoxifylline administration on
      patients with different stages of endometriosis on whom laparoscopy was
      performed. DESIGN: Prospective, double-blind, randomized, placebo-controlled
      clinical (Canadian Task Force classification I). SETTING: University and private
      hospitals. PATIENTS: Eighty-eight women, all with infertility, some with
      dysmenorrhea, dyspareunia, or pelvic pain, on whom a laparoscopic diagnosis of
      endometriosis was made. INTERVENTIONS: The treatment group received 800 mg
      pentoxifylline daily for 6 months immediately after surgery. The control group
      received placebo capsules. All patients were followed-up for 1 year thereafter.
      MEASUREMENTS AND MAIN RESULTS: A comparison of pregnancy rate and recurrence of
      signs and symptoms in the 2 groups was performed. Forty-three patients were
      studied in the pentoxifylline group and 45 in the placebo group. The cumulative
      pregnancy rate was 39.5% and 35.6% in the treatment and control groups,
      respectively. The overall recurrence of signs and symptoms was 14% in the former
      group and 15.6% in the latter. There were no statistically significant
      differences between the 2 groups in rates of pregnancy and recurrence (p = .700
      and .832, respectively). Nor was there any significant statistical difference
      between the same stages in the 2 groups regarding immunomodulation. CONCLUSIONS:
      According to the results of this study, and while keeping in mind that
      appropriate surgery is the main aspect of endometriosis treatment, there is no
      evidence that immunomodulation with pentoxifylline aids fertility or lessens
      recurrence of signs and symptoms in women with different stages of endometriosis
      (i.e., minimal, mild, moderate, or severe).

PMID- 17218231
TI  - Polypectomy in premenopausal women with abnormal uterine bleeding: effectiveness
      of hysteroscopic removal.
AB  - STUDY OBJECTIVE: To estimate the effectiveness of hysteroscopic polypectomy in
      premenopausal women with abnormal uterine bleeding and to identify prognostic
      factors for persistence or recurrence of symptoms after polypectomy. DESIGN:
      Retrospective study (Canadian Task Force classification II-3). SETTING:
      University teaching hospital. PATIENTS: Premenopausal women with abnormal uterine
      bleeding. INTERVENTION: Hysteroscopic polypectomy, regardless of whether combined
      with endometrial ablation or insertion of a levonorgestrel-releasing intrauterine
      device. MEASUREMENTS AND MAIN RESULTS: Seventy-eight consecutive patients met the
      inclusion criteria and were followed over time. Data were retrieved from medical
      records or from additional questionnaires sent to the patients. Failure of
      treatment was defined as persistence or recurrence of abnormal uterine bleeding
      after polypectomy, requiring further treatment. The mean age was 44.2 years (SD
      5.2, 95% CI 33.9-54.4 years). Intervention-free survival after polypectomy, as
      calculated by Kaplan-Meier survival analysis, was 41.1% (SE 8.3%, 95% CI 24.8%
      57.4%) after 4 years for patients who underwent only hysteroscopic polypectomy
      and 54.7% (SE 13.6%, 95% CI 28.0%-81.4%) for patients who underwent a polypectomy
      combined with endometrial ablation or insertion of a levonorgestrel-releasing
      intrauterine device (p = .08). Cox regression analyses revealed no statistically
      significant predictors for persistence or recurrence of symptoms after
      polypectomy. CONCLUSION: Nearly 60% of patients required further treatment for
      persistence or recurrence of abnormal uterine bleeding 4 years after
      hysteroscopic polypectomy. Although not significant, outcome of treatment tended
      to improve by combining polypectomy with either an endometrial ablation or
      insertion of a levonorgestrel-releasing intrauterine device.

PMID- 17218232
TI  - Partial small bowel obstruction and ileus following gynecologic laparoscopy.
AB  - STUDY OBJECTIVE: To assess the incidence and management of partial small bowel
      obstruction (PSBO) and ileus after gynecologic endoscopy. DESIGN: Internet-based
      cross-sectional survey (Canadian Task Force classification II-3). MATERIAL AND
      METHODS: An online survey was distributed to gynecologic surgeons to collect
      information about frequency and management of ileus and PSBO after gynecologic
      laparoscopy. MEASUREMENTS AND MAIN RESULTS: Of the 58 physician respondents, 22
      had managed at least 1 patient with PSBO or ileus after gynecologic laparoscopy.
      A total of 12 PSBOs and 14 patients experiencing ileus were identified for an
      overall incidence of 0.036%. Patients showed symptoms between 1 and 20 days
      postoperatively and had findings ranging from hypoactive (45%), to normal (30%),
      to hyperactive (25%) bowel sounds. Plain film radiographs (75%) were the most
      commonly used diagnostic modality followed by computed tomography (CT) scans of
      the abdomen. Most patients were initially managed with intestinal rest and
      nasogastric tube placement for 2 to 16 days. Fifty percent required a second
      procedure, with reported findings that included intestinal herniation (n = 7),
      bowel injury (n = 4), volvulus (n = 2), and urinoma (n = 1). CONCLUSION: Ileus
      and PSBO are rare findings after gynecologic laparoscopy. We identified 26 cases,
      most of which were initially managed conservatively. The majority of patients
      ultimately required a second operation. Surgeons should have a high index of
      suspicion when managing a patient with PSBO or ileus after gynecologic
      laparoscopy. Given the findings from the second procedures, CT scans would seem
      to be the diagnostic procedure of choice.

PMID- 17218233
TI  - Resectoscopic surgery may be an alternative to hysterectomy in high-risk women
      with atypical endometrial hyperplasia.
AB  - STUDY OBJECTIVE: Endometrial hyperplasia is found in 2% to 10% of women with
      abnormal uterine bleeding (AUB). Up to 43% of patients with cytologic atypia
      harbor coexisting adenocarcinoma, and approximately 20% to 52% of atypical
      hyperplasias, if untreated, progress to cancer. The objective of this study was
      to estimate the incidence of atypical endometrial hyperplasia encountered during
      routine resectoscopic surgery in women with AUB and to evaluate the role of
      resectoscopic surgery in the management of women with AUB and atypical
      endometrial hyperplasia who refused and/or were at high risk for hysterectomy.
      DESIGN: Prospective cohort study (Canadian Task Force classification II-3).
      SETTING: University-affiliated teaching hospital. PATIENTS: From January 1990
      through December 2005, the senior author (GAV) performed primary resectoscopic
      surgery in 3401 women with AUB. Among these, there were 22 women with atypical
      (17 complex, 5 simple) endometrial hyperplasia. INTERVENTIONS: All women
      underwent hysteroscopic evaluation and partial (n = 3) or complete (n = 19)
      endometrial electrocoagulation and/or resection. Subsequently, 6 women had
      hysterectomy and bilateral salpingo-oophorectomy (BSO). MEASUREMENTS AND MAIN
      RESULTS: The median (range) for age, parity, and body mass index were 55 years
      (24-78 years), 2 (0-4), and 30.1 kg/m2 (22.5-52.2 kg/m2), respectively. Among the
      3401 women, there were 22 cases of atypical endometrial hyperplasia, 12 of which
      were incidentally diagnosed at the time of hysteroscopy (complex 10, simple 2,
      incidence 0.35%). After hysteroscopic diagnosis or confirmation of diagnosis, 6
      women underwent hysterectomy and BSO. Of the remaining 16 women, followed for a
      median of 5 years (range 1.5-12 years), 1 was lost to follow-up, 1 had only a
      biopsy to preserve fertility, 1 died from lung cancer after 4 years, and 1 died
      from colon cancer after 5 years. One patient developed endometrial cancer after
      10.5 years with postmenopausal bleeding. She remains alive and well 3.5 years
      after hysterectomy and BSO. The remaining 11 patients are amenorrheic at a median
      follow-up of 6 years (range 1.5-12 years). CONCLUSIONS: Resectoscopic surgery in
      3391 women with AUB detected 12 incidental cases of atypical endometrial
      hyperplasia (incidence 0.35%). Skillful resectoscopic surgery may be an
      alternative to hysterectomy in women with AUB and atypical endometrial
      hyperplasia, who refuse or are at high-risk for hysterectomy and who are
      compliant with regular and long-term follow-up.

PMID- 17218234
TI  - Changing hysterectomy technique from open abdominal to laparoscopic: new trend in
      Oslo, Norway.
AB  - STUDY OBJECTIVE: To evaluate the change in hysterectomy technique. DESIGN:
      Retrospective study (Canadian Task Force classification XXX). SETTING: University
      tertiary referring center in Norway. PATIENTS: A total of 1963 women treated with
      hysterectomy over a 5-year period in Oslo. INTERVENTIONS: The operative records
      and techniques were investigated in all treated patients. MEASUREMENTS AND MAIN
      RESULTS: A total of 1963 hysterectomies were performed from 2001 through 2005.
      The operative patient records were investigated with the main focus on indication
      for surgery and the technique used in the operative procedure. In 2001, 62
      (17.7%) laparoscopic hysterectomies were performed, while 256 (73.1%) of the
      hysterectomies were done with laparotomy. The operative technique has gradually
      changed during the last 5 years. In 2005, 220 (53.5%) of the surgical procedures
      were laparoscopic, 177 (43.1%) were done by laparotomy, while the vaginal
      approach in all these years was less than 10%. CONCLUSION: From 2001 to 2005, a
      trend shift of the operative technique has been observed in Oslo, increasing the
      endoscopic hysterectomy rate from approximately 18% to 54%. During the same time,
      enlarged uteri with myomas equivalent to 10 to 12 weeks' gestation and
      endometrial cancer were more often treated by laparoscopic hysterectomy instead
      of open abdominal hysterectomy. With modern equipment and trained staff, more
      routine hysterectomies can be managed with laparoscopy.

PMID- 17218235
TI  - Prevention of complications in laparoscopic hysterectomy: experience with 1120
      cases performed by a single surgeon.
AB  - STUDY OBJECTIVE: The aim of this study is to describe a safe technique without
      any ureteral, bladder, and major vessel injuries in laparoscopic hysterectomy
      with a CO2 laser technique. DESIGN: Prospective study (Canadian Task Force
      classification II-3). SETTING: Centre Hospitalier Interregional Edith Cavell,
      Department of Obstetrics and Gynecology, Endoscopic Laser Surgery Center,
      Bruxelles, Belgium; and Kadir Has University, Metropolitan Florence Nightingale
      Hospital, Istanbul, Turkey. PATIENTS: One thousand one hundred twenty women with
      benign diseases. INTERVENTIONS: Laparoscopic-assisted vaginal hysterectomy (LAVH)
      or laparoscopic hysterectomy (LH). MEASUREMENTS AND MAIN RESULTS: Between 1992
      and 2004, in 1120 women with benign diseases, consecutive LAVH or LH was planned.
      During laparoscopic hysterectomy, at all stages, bipolar forceps was used for
      hemostasis, and a CO2 laser was used for vaporization and excision. The total
      operating time was 35 to 180 minutes, with a median of 52 minutes (range 35-163)
      for LAVH (n = 542) and 55 minutes (range 42-180) for LH (n = 552). Operations
      were successfully completed laparoscopically in 98.8% of the patients. The mean
      hospital stay was 2 days. The overall major complication rate was 1%. No
      ureteral, bladder, or major vascular injury occurred. CONCLUSION: The technique
      we used in our study is safe and effective in the prevention of ureteral,
      vesical, and vascular injuries during LAVH and LH; moreover, the use of bipolar
      coagulation and a CO2 laser in endoscopic surgery results in a shorter duration
      of operation. This technique provides all the advantages of both laparoscopic and
      vaginal surgery.

PMID- 17218236
TI  - NovaSure impedance controlled endometrial ablation: long-term follow-up results.
AB  - STUDY OBJECTIVE: A 7-year follow-up evaluation of the safety, efficacy, and long
      term outcome of endometrial ablation when using the NovaSure system in patients
      with menorrhagia secondary to abnormal uterine bleeding (AUB). DESIGN:
      Prospective, single-arm study (Canadian Task Force classification II-1). SETTING:
      St. Imre Teaching Hospital, Budapest, Hungary. PATIENTS: Seventy-five
      premenopausal women with menorrhagia secondary to AUB. INTERVENTIONS: Endometrial
      ablation using the NovaSure System without the use of endometrial pretreatment.
      MEASUREMENTS AND MAIN RESULTS: Loss of menstrual blood was measured using
      pictorial blood loss assessment chart diaries. Treatment times, complications,
      and rate of surgical re-interventions were recorded. No intra or postoperative
      complications were noted. Median follow-up period at the time was 7.8 years
      (range 6-8.6 years). The proportion of patients with fewer than 7 and 7 or more
      years of follow-up was 28.8% and 71.2%, respectively. The median treatment time
      was 92 seconds (range 40-120 seconds). At 7-year follow-up, 97.1% of evaluable
      patients reported amenorrhea. However, all patients (100%, actuarial rate: 97%
      with 95% CI [83%-100%]) experienced a successful reduction in bleeding to normal
      levels or less. Six of 75 patients underwent hysterectomy, and one of 75 had a
      repeat ablation representing a total of 92% (95% CI: 83%-96%) avoidance of
      additional surgery during the follow-up period. CONCLUSIONS: Clinical results
      demonstrate that the use of NovaSure System is safe and effective, with a low
      rate of surgical re-intervention at 7-year follow-up.

PMID- 17218237
TI  - Comparison of the different types of "laparoscopic total hysterectomy".
AB  - STUDY OBJECTIVE: To review the operative outcomes among different types of
      laparoscopic total hysterectomy (LH) classified according to the Munro and Parker
      classification system. DESIGN: Prospective observational cohort study (Canadian
      Task Force classification II). SETTING: 6 major public hospitals in Hong Kong.
      PATIENTS: 143 patients underwent LH in a 6-month period. INTERVENTIONS: Type I to
      type IV LH according to the Munro and Parker classification system. MEASUREMENTS
      AND MAIN RESULTS: We studied 56 type I, 49 type II, 25 type III, and 13 type IV
      LH. The median operative time was 105 minutes, which was significantly longer in
      the type IV LH group (160 minutes). The median blood loss was significantly
      higher in the type I LH group (300 mL). The incidence of urinary tract infection
      in type I LH was 8.9%, which was significantly higher than other LH groups. The
      overall operative complication rate was 20.3%, which was highest in the type III
      hysterectomy group (36%), although the difference did not reach statistical
      significance among the various types of hysterectomy groups. CONCLUSION: There
      has been a change from abdominal hysterectomy to LH in the past decades, and it
      is time for us to explore the best type of LH. Our findings suggest that type I
      LH is associated with significantly more blood loss and urinary tract infection;
      whereas type IV LH is associated with significantly longer operating time.
      However, we still cannot conclude which is the best type of LH until results from
      a randomized controlled trial will become available.

PMID- 17218238
TI  - Retrospective cost analysis comparing Essure hysteroscopic sterilization and
      laparoscopic bilateral tubal coagulation.
AB  - STUDY OBJECTIVE: To compare the institutional cost of permanent female
      sterilization by Essure hysteroscopic sterilization and laparoscopic bilateral
      coagulation. DESIGN: Retrospective cohort study (Canadian Task Force
      classification II-2). SETTING: Midwestern academic medical center. PATIENTS:
      Women of reproductive age who elected for permanent contraception by the Essure
      method (n = 43) or by laparoscopic tubal coagulation (n = 44) during the time
      frame studied. INTERVENTIONS: Placement of the Essure inserts according to the
      manufacturer's instructions or laparoscopic tubal sterilization using bipolar
      forceps according to standard techniques of open or closed laparoscopy.
      MEASUREMENTS AND MAIN RESULTS: Cost-center data for the institutional cost of the
      procedure was abstracted for each patient included in the study. In addition,
      demographic data and procedural information were obtained and compared for the
      patient populations. The Essure system of hysteroscopic sterilization had a
      significantly decreased cost compared with laparoscopic tubal sterilization when
      both procedures were performed in an operating room setting. The decrease per
      patient in institutional cost was 180 dollars (p = .038). This included the cost
      of the confirmatory hysterosalpingogram 3 months after Essure placement and the
      cost of laparoscopic tubal occlusion by Filshie clip if the Essure micro-inserts
      could not be placed. The majority of the cost was related to hospital costs as
      opposed to physician costs. The Essure procedure had higher costs for disposable
      equipment (p <.0001), but this was offset by higher charges for operating room
      costs, which included the recovery room (p <.0001) and pharmacy costs (p <.0001)
      in the patients in the laparoscopy group. CONCLUSION: In our setting, the Essure
      hysteroscopic sterilization had significant cost savings compared with
      laparoscopic tubal sterilization (p = .038). We believe that our data represent
      the minimum of potential savings using this approach, and future developments
      will only increase the cost difference found in our study.

PMID- 17218239
TI  - The real intraabdominal pressure during laparoscopy: comparison of different
      insufflators.
AB  - STUDY OBJECTIVE: To compare 5 laparoscopic insufflators with different gas flow
      rates with regard to accuracy of preset pressure setting versus real
      intraoperative intraabdominal pressure. DESIGN: Prospective study (Canadian Task
      Force classification II-2). SETTING: Fayette Medical Center, Alabama. PATIENTS:
      Five patients undergoing laparoscopic cholecystectomy. INTERVENTIONS:
      Intraoperative intraabdominal and system pressure measurements during comparable
      laparoscopic procedures. MEASUREMENTS AND MAIN RESULTS: Actual intraabdominal
      pressure was measured and compared between 5 different 10 to 20 L/min
      insufflators (Storz Laparoflator and Endoflator, Richard Wolf, BEI Medical and
      Snowden & Pencer) with a computer-based online data acquisition system. At a
      nominal pressure of 10 mm Hg, the mean intraabdominal pressure during the entire
      procedure was measured to be between 9.68 and 11.45 mm Hg. The mean
      intraabdominal pressure during laparoscopy for the insufflators showed a margin
      of error of 14.5%, with maximum intraabdominal pressure peaks measured between
      14.65 and 17.87 mm Hg. CONCLUSIONS: Within an error margin of <15% of the preset
      intraabdominal pressure setting, the insufflators evaluated can be considered
      pressure reliable. Although intraabdominal pressure peaks exceeding the nominal
      pressure temporarily reached up to 78.7% of the setting, no apparent
      complications were observed. Excessive pressure peaks seen in the previous
      reported laboratory model could not be confirmed during in vivo application.

PMID- 17218240
TI  - Minilaparotomy hysterectomy assisted by self-retaining elastic abdominal
      retractor.
AB  - STUDY OBJECTIVE: To verify the efficacy and safety of minilaparotomy hysterectomy
      using a self-retaining elastic abdominal retractor. DESIGN: Retrospective study
      (Canadian Task Force classification II-3). SETTING: Private hospital, department
      of obstetrics and gynecology. PATIENTS: One-hundred-fifty women, age 37 to 76
      years, with benign uterine pathology or preinvasive neoplasia. INTERVENTION:
      Minilaparotomy hysterectomy assisted by a self-retaining elastic abdominal
      retractor. MEASUREMENTS AND MAIN RESULTS: The mean surgical time was 70 +/- 23.5
      minutes (95% CI 63.1-70.7). There were no intraoperative complications. There was
      no need to extend the initial incision. Eight patients developed complications
      during the immediate postoperative period (fever in 2, hematoma of the surgical
      wound in 2, sub-aponeurotic seroma in 2, pubic edema in 1, and pulmonary embolism
      in 1). During the late postoperative period, a vaginal cuff dehiscence was
      reported. Mean postoperative hospital stay was 2.5 +/- 0.2 days (95% CI 2.4-2.6).
      CONCLUSION: Minilaparotomy hysterectomy assisted by a self-retaining abdominal
      elastic retractor is a safe and effective minimally invasive procedure. Also, it
      appears to be a good alternative to laparoscopic hysterectomy for institutions
      that do not have the required expensive equipment or for gynecologists who do not
      have laparoscopic experience.

PMID- 17218241
TI  - Laparoscopic treatment of recurrent small bowel obstruction secondary to ileal
      endometriosis.
AB  - Endometriosis is a relatively common condition characterized by implantation and
      proliferation of endometrial glands outside the uterus affecting 8% to 15% of
      women. Intestinal involvement is common, reported in 12% to 37% of individuals
      with the disease. The sites most often affected are the sigmoid colon and rectum
      (85%), while small bowel involvement is seen less frequently (7%) and usually
      confined to the distal ileum. The cecum (3.6%) and appendix (3%) are the sites
      least affected.

PMID- 17218242
TI  - Late postoperative urinary stress incontinence after a laparoscopic-assisted
      Vecchietti procedure for neovagina creation in a patient with Rokitansky
      syndrome: successful treatment with the TVT-O technique.
AB  - A case report of urinary stress incontinence after surgery in a 20-year-old
      patient with Mayer-Rokitansky-Kuster-Hauser syndrome is presented. A neovagina
      was successfully created with a laparoscopic-assisted Vecchietti procedure.
      Fifteen months later, after normal and satisfactory sexual intercourse, the
      patient was seen for stress urinary incontinence. A second surgery consistent
      with the transobturator tension-free vaginal tape (TVT) system with nonelastic
      polypropylene suburethral TVT allowed full correction of the urinary symptoms.

PMID- 17218243
TI  - Endometrioid adenocarcinoma treated by hysteroscopic endomyometrial resection.
AB  - A 53-year-old multiparous woman, with no identifiable risk factor for endometrial
      cancer, presented with menorrhagia. She had been treated with oral contraceptives
      for 3 years. Office endometrial biopsy indicated well-differentiated
      villoglandular adenocarcinoma of the endometrium. The patient refused
      hysterectomy and would consent only to hysteroscopic resection. She remains alive
      and well, with no clinical evidence of recurrence 5 years after resection. We
      propose that skillful resectoscopic surgery, under specific circumstance, may be
      an appropriate alternative treatment to hysterectomy for some early uterine
      malignancies.

PMID- 17218244
TI  - Multiple leiomyomas after laparoscopic hysterectomy: report of two cases.
AB  - We report on 2 cases of multiple leiomyomas arising in the pelvis after
      laparoscopic hysterectomy. One patient underwent laparoscopic myomectomy at 41
      years of age and subsequently had a total laparoscopic hysterectomy for myomas 4
      years later. Three years post-hysterectomy, she presented with pelvic masses that
      were removed laparoscopically and were leiomyomas on histopathologic examination.
      The other patient underwent supracervical hysterectomy for myomas with removal of
      a parasitic myoma from underneath the dome of the diaphragm. Eight months post
      hysterectomy, she came to our office with a pelvic mass with a large myoma that
      was removed laparoscopically. Disseminated leiomyomas may occur after
      hysterectomy; and though various theories have been proposed to explain this
      remarkable entity, none has found universal acceptance. A thorough MEDLINE search
      did not reveal any reports of large pelvic masses of this size after hysterectomy
      or their management laparoscopically, and these are probably the first reported
      cases.

PMID- 17218245
TI  - Septate uterus with double cervices, unilaterally obstructed vaginal septum, and
      ipsilateral renal agenesis: a rare combination of mullerian and wolffian
      anomalies complicated by severe endometriosis in an adolescent.
AB  - We present a previously unreported combination of mullerian and wolffian
      anomalies of a septate uterus with double cervices, unilaterally obstructed
      vaginal septum, and ipsilateral renal agenesis; this constellation of findings
      may offer clues that could modify classic embryologic explanations. In spite of
      the young age of our patient (15-years old), a chief complaint of malodorous
      vaginal discharge, and absence of dysmenorrhea or any other symptoms of
      endometriosis, laparoscopic examination revealed severe endometriosis with dense
      adhesions, probably as a result of abundant menstrual regurgitation. Laparoscopic
      resection of endometriotic lesions, adhesiolysis, and vaginoscopic septotomy were
      successfully performed while preserving hymenal integrity.

PMID- 17218247
TI  - A mouse for all reasons.
AB  - Three major mouse knockout programs are underway worldwide, working together to
      mutate all protein-encoding genes in the mouse using a combination of gene
      trapping and gene targeting in mouse embryonic stem (ES) cells. Although the
      current emphasis is on production of this valuable resource, there are
      significant efforts to facilitate program coordination, to enhance the
      availability of this resource, and to plan for future efforts in mouse genetics
      research.

PMID- 17218248
TI  - Jawing about TNF: new hope for cherubism.
AB  - Mutations in the SH3-domain binding protein 2 (SH3BP2) are known to cause a rare
      childhood disorder called cherubism that is characterized by inflammation and
      bone loss in the jaw, but the mechanism has remained unclear. In this issue, Ueki
      et al. (Ueki et al., 2007) now demonstrate that a cherubism mutation activates
      mouse Sh3bp2 resulting in enhanced production of the cytokine TNF-alpha by
      myeloid cells, leading to both bone loss and inflammation.

PMID- 17218249
TI  - Hairy math: insights into hair-follicle spacing and orientation.
AB  - Hair follicles in the skin have a characteristic spacing and orientation. Two
      recent papers (Sick et al., 2006 and Wang et al., 2006) report the use of
      contrasting mathematical models and experimental manipulations to gain insight
      into the mechanisms underlying patterns of hair-follicle distribution and
      orientation.

PMID- 17218250
TI  - Polo delivers a PICH to the kinetochore.
AB  - In this issue, Baumann et al. (2007) identify a helicase PICH that localizes to
      "threads" that remain connected between sister kinetochores after they have
      separated in anaphase. These threads are thought to be catenated centromeric DNA.
      PICH contributes to the mitotic checkpoint by recruiting Mad2 to kinetochores and
      is proposed to regulate checkpoint signaling by monitoring tension at
      centromeres.

PMID- 17218251
TI  - A circadian sleep disorder reveals a complex clock.
AB  - Circadian rhythms are established by transcription of clock genes and
      autoregulatory transcriptional feedback loops. In this issue, Xu et al. (2007)
      characterize mice expressing a human Per2 mutation identified in patients with
      familial advanced sleep phase syndrome. Their results reveal that PER2
      phosphorylation, by CK1delta and other kinases, is surprisingly complex and has
      opposite effects on PER2 levels and period length.

PMID- 17218252
TI  - PTEN enters the nuclear age.
AB  - Regulation of the PTEN tumor suppressor protein is poorly understood. In this
      issue, Wang et al. (2007) and Trotman et al. (2007) describe how ubiquitination
      regulates PTEN stability and its nuclear localization. Additionally, Shen et al.
      (2007) report that a nuclear pool of PTEN helps to maintain chromosomal
      stability.

PMID- 17218253
TI  - Trekking across the brain: the journey of neuronal migration.
AB  - The correct positioning of neurons during development--achieved through directed
      migration--is the basis for proper brain function. Several decades of research
      have yielded a comprehensive map illustrating the temporal and spatial events
      underlying neurogenesis and neuronal migration during development. The discovery
      of distinct migration modes and pathways has been accompanied by the
      identification of a large interwoven molecular network that transmits
      extracellular signals into the cell. Moreover, recent work has shed new light on
      how the cytoskeleton is regulated and coordinated at the molecular and cellular
      level to execute neuronal migration.

PMID- 17218254
TI  - Mutations in alpha-tubulin cause abnormal neuronal migration in mice and
      lissencephaly in humans.
AB  - The development of the mammalian brain is dependent on extensive neuronal
      migration. Mutations in mice and humans that affect neuronal migration result in
      abnormal lamination of brain structures with associated behavioral deficits.
      Here, we report the identification of a hyperactive N-ethyl-N-nitrosourea (ENU)
      induced mouse mutant with abnormalities in the laminar architecture of the
      hippocampus and cortex, accompanied by impaired neuronal migration. We show that
      the causative mutation lies in the guanosine triphosphate (GTP) binding pocket of
      alpha-1 tubulin (Tuba1) and affects tubulin heterodimer formation. Phenotypic
      similarity with existing mouse models of lissencephaly led us to screen a cohort
      of patients with developmental brain anomalies. We identified two patients with
      de novo mutations in TUBA3, the human homolog of Tuba1. This study demonstrates
      the utility of ENU mutagenesis in the mouse as a means to discover the basis of
      human neurodevelopmental disorders.

PMID- 17218255
TI  - Modeling of a human circadian mutation yields insights into clock regulation by
      PER2.
AB  - Circadian rhythms are endogenous oscillations of physiological and behavioral
      phenomena with period length of approximately 24 hr. A mutation in human Period 2
      (hPER2), a gene crucial for resetting the central clock in response to light, is
      associated with familial advanced sleep phase syndrome (FASPS), an autosomal
      dominant condition with early morning awakening and early sleep times. The FASPS
      hPER2 S662G mutation resulted in PER2 being hypophosphorylated by casein kinase I
      (CKI) in vitro. We generated transgenic mice carrying the FASPS hPER2 S662G
      mutation and faithfully recapitulate the human phenotype. We show that
      phosphorylation at S662 leads to increased PER2 transcription and suggest that
      phosphorylation at another site leads to PER2 degradation. Altering CKIdelta
      dosage modulates the S662 phenotype demonstrating that CKIdelta can regulate
      period through PER2 in vivo. Modeling a naturally occurring human variant in mice
      has yielded novel insights into PER2 regulation.

PMID- 17218256
TI  - Increased myeloid cell responses to M-CSF and RANKL cause bone loss and
      inflammation in SH3BP2 "cherubism" mice.
AB  - While studies of the adaptor SH3BP2 have implicated a role in receptor-mediated
      signaling in mast cells and lymphocytes, they have failed to identify its
      function or explain why SH3BP2 missense mutations cause bone loss and
      inflammation in patients with cherubism. We demonstrate that Sh3bp2 "cherubism"
      mice exhibit trabecular bone loss, TNF-alpha-dependent systemic inflammation, and
      cortical bone erosion. The mutant phenotype is lymphocyte independent and can be
      transferred to mice carrying wild-type Sh3bp2 alleles through mutant fetal liver
      cells. Mutant myeloid cells show increased responses to M-CSF and RANKL
      stimulation, and, through mechanisms of increased ERK 1/2 and SYK
      phosphorylation/activation, they form macrophages that express high levels of TNF
      alpha and osteoclasts that are unusually large. M-CSF and RANKL stimulation of
      myeloid cells that overexpress wild-type SH3BP2 results in similar large
      osteoclasts. This indicates that the mutant phenotype reflects gain of SH3BP2
      function and suggests that SH3BP2 is a critical regulator of myeloid cell
      responses to M-CSF and RANKL stimulation.

PMID- 17218257
TI  - The origin recognition complex functions in sister-chromatid cohesion in
      Saccharomyces cerevisiae.
AB  - High-fidelity chromosomal segregation requires the properly timed establishment
      of sister-chromatid cohesion mediated by the Cohesin complex, and its resolution
      at the metaphase-to-anaphase transition. We have examined cell-cycle progression
      in a yeast strain from which the origin recognition complex protein Orc2 was
      depleted after the assembly of prereplication complexes. We find that Orc2
      depletion causes a delay in progression through mitosis, reflecting activation of
      both the DNA-damage and Mad2-spindle checkpoints. Surprisingly, sister-chromatid
      cohesion is impaired in Orc2-depleted cells, although Cohesin subunits are
      properly associated with chromatin. Reexpression of Orc2 in late G2/M phase
      restores chromatid cohesion. Finally, the targeting of Orc2 to a specific
      chromosomal locus suppresses premature sister-chromatid separation locally in a
      temperature-sensitive cohesin mutant. We conclude that ORC mediates sister
      chromatid interaction on a pathway that is additive with Cohesin-mediated
      pairing.

PMID- 17218258
TI  - PICH, a centromere-associated SNF2 family ATPase, is regulated by Plk1 and
      required for the spindle checkpoint.
AB  - We identify PICH (Plk1-interacting checkpoint "helicase"), a member of the SNF2
      ATPase family, as an interaction partner and substrate of Plk1. Following
      phosphorylation of PICH on the Cdk1 site T1063, Plk1 is recruited to PICH and
      controls its localization. Starting in prometaphase, PICH accumulates at
      kinetochores and inner centromeres. Moreover, it decorates threads that form
      during metaphase before increasing in length and progressively diminishing during
      anaphase. PICH-positive threads connect sister kinetochores and are dependent on
      tension, sensitive to DNase, and exacerbated in response to premature loss of
      cohesins or inhibition of topoisomerase II, suggesting that they represent
      stretched centromeric chromatin. Depletion of PICH causes the selective loss of
      Mad2 from kinetochores and completely abrogates the spindle checkpoint, resulting
      in massive chromosome missegregation. These data identify PICH as a novel
      essential component of checkpoint signaling. We propose that PICH binds to
      catenated centromere-related DNA to monitor tension developing between sister
      kinetochores.

PMID- 17218259
TI  - The C. elegans RSA complex localizes protein phosphatase 2A to centrosomes and
      regulates mitotic spindle assembly.
AB  - Microtubule behavior changes during the cell cycle and during spindle assembly.
      However, it remains unclear how these changes are regulated and coordinated. We
      describe a complex that targets the Protein Phosphatase 2A holoenzyme (PP2A) to
      centrosomes in C. elegans embryos. This complex includes Regulator of Spindle
      Assembly 1 (RSA-1), a targeting subunit for PP2A, and RSA-2, a protein that binds
      and recruits RSA-1 to centrosomes. In contrast to the multiple functions of the
      PP2A catalytic subunit, RSA-1 and RSA-2 are specifically required for microtubule
      outgrowth from centrosomes and for spindle assembly. The centrosomally localized
      RSA-PP2A complex mediates these functions in part by regulating two critical
      mitotic effectors: the microtubule destabilizer KLP-7 and the C. elegans
      regulator of spindle assembly TPXL-1. By regulating a subset of PP2A functions at
      the centrosome, the RSA complex could therefore provide a means of coordinating
      microtubule outgrowth from centrosomes and kinetochore microtubule stability
      during mitotic spindle assembly.

PMID- 17218260
TI  - NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN.
AB  - The tumor suppressor PTEN, a critical regulator for multiple cellular processes,
      is mutated or deleted frequently in various human cancers. Subtle reductions in
      PTEN expression levels have profound impacts on carcinogenesis. Here we show that
      PTEN level is regulated by ubiquitin-mediated proteasomal degradation, and
      purified its ubiquitin ligase as HECT-domain protein NEDD4-1. In cells NEDD4-1
      negatively regulates PTEN stability by catalyzing PTEN polyubiquitination.
      Consistent with the tumor-suppressive role of PTEN, overexpression of NEDD4-1
      potentiated cellular transformation. Strikingly, in a mouse cancer model and
      multiple human cancer samples where the genetic background of PTEN was normal but
      its protein levels were low, NEDD4-1 was highly expressed, suggesting that
      aberrant upregulation of NEDD4-1 can posttranslationally suppress PTEN in
      cancers. Elimination of NEDD4-1 expression inhibited xenotransplanted tumor
      growth in a PTEN-dependent manner. Therefore, NEDD4-1 is a potential proto
      oncogene that negatively regulates PTEN via ubiquitination, a paradigm analogous
      to that of Mdm2 and p53.

PMID- 17218261
TI  - Ubiquitination regulates PTEN nuclear import and tumor suppression.
AB  - The PTEN tumor suppressor is frequently affected in cancer cells, and inherited
      PTEN mutation causes cancer-susceptibility conditions such as Cowden syndrome.
      PTEN acts as a plasma-membrane lipid-phosphatase antagonizing the
      phosphoinositide 3-kinase/AKT cell survival pathway. However, PTEN is also found
      in cell nuclei, but mechanism, function, and relevance of nuclear localization
      remain unclear. We show that nuclear PTEN is essential for tumor suppression and
      that PTEN nuclear import is mediated by its monoubiquitination. A lysine mutant
      of PTEN, K289E associated with Cowden syndrome, retains catalytic activity but
      fails to accumulate in nuclei of patient tissue due to an import defect. We
      identify this and another lysine residue as major monoubiquitination sites
      essential for PTEN import. While nuclear PTEN is stable, polyubiquitination leads
      to its degradation in the cytoplasm. Thus, we identify cancer-associated
      mutations of PTEN that target its posttranslational modification and demonstrate
      how a discrete molecular mechanism dictates tumor progression by differentiating
      between degradation and protection of PTEN.

PMID- 17218262
TI  - Essential role for nuclear PTEN in maintaining chromosomal integrity.
AB  - A broad spectrum of mutations in PTEN, encoding a lipid phosphatase that
      inactivates the P13-K/AKT pathway, is found associated with primary tumors. Some
      of these mutations occur outside the phosphatase domain, suggesting that
      additional activities of PTEN function in tumor suppression. We report a nuclear
      function for PTEN in controlling chromosomal integrity. Disruption of Pten leads
      to extensive centromere breakage and chromosomal translocations. PTEN was found
      localized at centromeres and physically associated with CENP-C, an integral
      component of the kinetochore. C-terminal PTEN mutants disrupt the association of
      PTEN with centromeres and cause centromeric instability. Furthermore, Pten null
      cells exhibit spontaneous DNA double-strand breaks (DSBs). We show that PTEN acts
      on chromatin and regulates expression of Rad51, which reduces the incidence of
      spontaneous DSBs. Our results demonstrate that PTEN plays a fundamental role in
      the maintenance of chromosomal stability through the physical interaction with
      centromeres and control of DNA repair. We propose that PTEN acts as a guardian of
      genome integrity.

PMID- 17218263
TI  - Structural basis of integrin activation by talin.
AB  - Regulation of integrin affinity (activation) is essential for metazoan
      development and for many pathological processes. Binding of the talin
      phosphotyrosine-binding (PTB) domain to integrin beta subunit cytoplasmic domains
      (tails) causes activation, whereas numerous other PTB-domain-containing proteins
      bind integrins without activating them. Here we define the structure of a complex
      between talin and the membrane-proximal integrin beta3 cytoplasmic domain and
      identify specific contacts between talin and the integrin tail required for
      activation. We used structure-based mutagenesis to engineer talin and beta3
      variants that interact with comparable affinity to the wild-type proteins but
      inhibit integrin activation by competing with endogenous talin. These results
      reveal the structural basis of talin's unique ability to activate integrins,
      identify an interaction that could aid in the design of therapeutics to block
      integrin activation, and enable engineering of cells with defects in the
      activation of multiple classes of integrins.

PMID- 17218264
TI  - Selective activation of cognate SNAREpins by Sec1/Munc18 proteins.
AB  - Sec1/Munc18 (SM) proteins are required for every step of intracellular membrane
      fusion, but their molecular mechanism of action has been unclear. In this work,
      we demonstrate a fundamental role of the SM protein: to act as a stimulatory
      subunit of its cognate SNARE fusion machinery. In a reconstituted system,
      mammalian SNARE pairs assemble between bilayers to drive a basal fusion reaction.
      Munc18-1/nSec1, a synaptic SM protein required for neurotransmitter release,
      strongly accelerates this reaction through direct contact with both t- and v
      SNAREs. Munc18-1 accelerates fusion only for the cognate SNAREs for exocytosis,
      therefore enhancing fusion specificity.

PMID- 17218265
TI  - Manipulating the mouse genome to engineer precise functional syntenic
      replacements with human sequence.
AB  - We have devised a strategy (called recombinase-mediated genomic replacement,
      RMGR) to allow the replacement of large segments (>100 kb) of the mouse genome
      with the equivalent human syntenic region. The technique involves modifying a
      mouse ES cell chromosome and a human BAC by inserting heterotypic lox sites to
      flank the proposed exchange interval and then using Cre recombinase to achieve
      segmental exchange. We have demonstrated the feasibility of this approach by
      replacing the mouse alpha globin regulatory domain with the human syntenic region
      and generating homozygous mice that produce only human alpha globin chains.
      Furthermore, modified ES cells can be used iteratively for functional studies,
      and here, as an example, we have used RMGR to produce an accurate mouse model of
      human alpha thalassemia. RMGR has general applicability and will overcome
      limitations inherent in current transgenic technology when studying the
      expression of human genes and modeling human genetic diseases.

PMID- 17218266
TI  - Role of the sigma factor in transcription initiation in the absence of core RNA
      polymerase.

PMID- 17218267
TI  - Dynamic regulation of histone lysine methylation by demethylases.
AB  - Recent studies demonstrated that histone methylation is not static but is
      dynamically regulated by histone methyltransferases and the newly discovered
      histone demethylases. This review discusses the chemical mechanisms for the known
      and potentially new classes of demethylases, the roles of these demethylases in
      chromatin and transcription, and their potential biological functions and
      connections to human diseases.

PMID- 17218268
TI  - Methylation of lysine 4 on histone H3: intricacy of writing and reading a single
      epigenetic mark.
AB  - Cells employ elaborate mechanisms to introduce structural and chemical variation
      into chromatin. Here, we focus on one such element of variation: methylation of
      lysine 4 in histone H3 (H3K4). We assess a growing body of literature, including
      treatment of how the mark is established, the patterns of methylation, and the
      functional consequences of this epigenetic signature. We discuss structural
      aspects of the H3K4 methyl recognition by the downstream effectors and propose a
      distinction between sequence-specific recruitment mechanisms and stabilization on
      chromatin through methyl-lysine recognition. Finally, we hypothesize how the
      unique properties of the polyvalent chromatin fiber and associated effectors may
      amplify small differences in methyl-lysine recognition, simultaneously allowing
      for a dynamic chromatin architecture.

PMID- 17218269
TI  - Gcn5 promotes acetylation, eviction, and methylation of nucleosomes in
      transcribed coding regions.
AB  - We report that coactivator SAGA, containing the HAT Gcn5p, occupies the GAL1 and
      ARG1 coding sequences during transcriptional induction, dependent on PIC assembly
      and Ser5 phosphorylation of the Pol II CTD. Induction of GAL1 increases H3
      acetylation per nucleosome in the ORF, dependent on SAGA integrity but not the
      alternative Gcn5p-HAT complex ADA. Unexpectedly, H3 acetylation in ARG1 coding
      sequences does not increase during induction due to the opposing activities of
      multiple HDAs associated with the ORF. Remarkably, inactivation of Gcn5p
      decreases nucleosome eviction from both GAL1 and a long ( approximately 8 kb) ORF
      transcribed from the GAL1 promoter. This is associated with reduced Pol II
      occupancy at the 3' end and decreased mRNA production, selectively, for the long
      ORF. Gcn5p also enhances H3-K4 trimethylation in the ARG1 ORF and bulk histones.
      Thus, Gcn5p, most likely in SAGA, stimulates modification and eviction of
      nucleosomes in transcribed coding sequences and promotes Pol II elongation.

PMID- 17218270
TI  - Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch.
AB  - In mammals, inactivation of one X chromosome in the female equalizes gene dosages
      between XX females and XY males. Two noncoding loci, Tsix and Xite, together
      regulate X chromosome fate by controlling homologous chromosome pairing,
      counting, and mutually exclusive choice. Following choice, the asymmetry of Xite
      and Tsix expression drives divergent chromosome fates, but how this pattern
      becomes established is currently unknown. Although no proven trans-acting factors
      have been identified, a likely candidate is Ctcf, a chromatin insulator with
      essential function in autosomal imprinting. Here, we search for trans-factors and
      identify Yy1 as a required cofactor for Ctcf. Paired Ctcf-Yy1 elements are highly
      clustered within the counting/choice and imprinting domain of Tsix. A deficiency
      of Yy1 leads to aberrant Tsix and Xist expression, resulting in a deficit of male
      and female embryos. Yy1 and Ctcf associate through specific protein-protein
      interactions and together transactivate Tsix. We propose that the Ctcf-Yy1-Tsix
      complex functions as a key component of the X chromosome binary switch.

PMID- 17218272
TI  - The arginine methyltransferase CARM1 regulates the coupling of transcription and
      mRNA processing.
AB  - The coactivator-associated arginine methyltransferase CARM1 is recruited by many
      different transcription factors as a positive regulator. To understand the
      mechanism by which CARM1 functions, we sought to isolate its substrates. We
      developed a small-pool screening approach for this purpose and identified CA150,
      SAP49, SmB, and U1C as splicing factors that are specifically methylated by
      CARM1. We further showed that CA150, a molecule that links transcription to
      splicing, interacts with the Tudor domain of the spinal muscular atrophy protein
      SMN in a CARM1-dependent fashion. Experiments with an exogenous splicing reporter
      and the endogenous CD44 gene revealed that CARM1 promotes exon skipping in an
      enzyme-dependent manner. The identification of splicing factors that are
      methylated by CARM1, and protein-protein interactions that are regulated by
      CARM1, strongly implicates this enzyme in the regulation of alternative splicing
      and points toward its involvement in spinal muscular atrophy pathogenesis.

PMID- 17218271
TI  - Parallel SUMOylation-dependent pathways mediate gene- and signal-specific
      transrepression by LXRs and PPARgamma.
AB  - Transrepression is widely utilized to negatively regulate gene expression, but
      the mechanisms by which different nuclear receptors effect gene- and signal
      specific transrepression programs remain poorly understood. Here, we report the
      identification of alternative SUMOylation-dependent mechanisms that enable
      PPARgamma and LXRs to negatively regulate overlapping but distinct subsets of
      proinflammatory genes. Ligand-dependent conjugation of SUMO2/3 to LXRs or SUMO1
      to PPARgamma targets them to promoters of TLR target genes, where they prevent
      the signal-dependent removal of NCoR corepressor complexes required for
      transcriptional activation. SUMO1-PPARgamma and SUMO2/3-LXRs inhibit distinct
      NCoR clearance mechanisms, allowing promoter- and TLR-specific patterns of
      repression. Mutational analysis and studies of naturally occurring oxysterol
      ligands indicate that the transactivation and SUMOylation-dependent
      transrepression activities of LXRs can be independently regulated. These studies
      define parallel but functionally distinct pathways that are utilized by PPARgamma
      and LXRs to differentially regulate complex programs of gene expression that
      control immunity and homeostasis.

PMID- 17218273
TI  - Unconventional mechanism of mRNA capping by the RNA-dependent RNA polymerase of
      vesicular stomatitis virus.
AB  - All known eukaryotic and some viral mRNA capping enzymes (CEs) transfer a GMP
      moiety of GTP to the 5'-diphosphate end of the acceptor RNA via a covalent enzyme
      GMP intermediate to generate the cap structure. In striking contrast, the
      putative CE of vesicular stomatitis virus (VSV), a prototype of nonsegmented
      negative-strand (NNS) RNA viruses including rabies, measles, and Ebola,
      incorporates the GDP moiety of GTP into the cap structure of transcribing mRNAs.
      Here, we report that the RNA-dependent RNA polymerase L protein of VSV catalyzes
      the capping reaction by an RNA:GDP polyribonucleotidyltransferase activity, in
      which a 5'-monophosphorylated viral mRNA-start sequence is transferred to GDP
      generated from GTP via a covalent enzyme-RNA intermediate. Thus, the L proteins
      of VSV and, by extension, other NNS RNA viruses represent a new class of viral
      CEs, which have evolved independently from known eukaryotic CEs.

PMID- 17218274
TI  - Cytokines direct the regulation of Bim mRNA stability by heat-shock cognate
      protein 70.
AB  - Previous gene-targeting studies indicated that Bim, a BH3-only death activator,
      regulates total blood cell number. Cytokines contribute to this process by
      negatively regulating steady-state levels of Bim mRNA. Here we present a
      molecular mechanism for cytokine-mediated posttranscriptional regulation of Bim
      mRNA by heat-shock cognate protein 70 (Hsc70), which binds to AU-rich elements
      (AREs) in the 3'-untranslated region of specific mRNAs and enhances their
      stability. The RNA binding potential of Hsc70 is regulated by cochaperones
      including Bag-4 (also SODD), CHIP, Hip, and Hsp40. Cytokines regulate the
      expression or function of these cochaperones by activating Ras pathways. Thus,
      exposure of cells to cytokines ultimately leads to destabilization of Bim mRNA
      and promotion of cell survival. This unanticipated role of a
      chaperone/cochaperone complex in mRNA stability appears to be critical for
      hematopoiesis and leukemogenesis.

PMID- 17218276
TI  - Kinase-independent function of cyclin E.
AB  - E-type cyclins are thought to drive cell-cycle progression by activating cyclin
      dependent kinases, primarily CDK2. We previously found that cyclin E-null cells
      failed to incorporate MCM helicase into DNA prereplication complex during G(0) -
      > S phase progression. We now report that a kinase-deficient cyclin E mutant can
      partially restore MCM loading and S phase entry in cyclin E-null cells. We found
      that cyclin E is loaded onto chromatin during G(0) --> S progression. In the
      absence of cyclin E, CDT1 is normally loaded onto chromatin, whereas MCM is not,
      indicating that cyclin E acts between CDT1 and MCM loading. We observed a
      physical association of cyclin E with CDT1 and with MCMs. We propose that cyclin
      E facilitates MCM loading in a kinase-independent fashion, through physical
      interaction with CDT1 and MCM. Our work indicates that-in addition to their
      function as CDK activators-E cyclins play kinase-independent functions in cell
      cycle progression.

PMID- 17218277
TI  - Structural evidence for a common intermediate in small G protein-GEF reactions.
AB  - Rho of plants (Rop) proteins belong to the superfamily of small GTP-binding (G)
      proteins and are vital regulators of signal transduction in plants. In order to
      become activated, Rop proteins need to exchange GDP for GTP, an intrinsically
      slow process catalyzed by guanine nucleotide exchange factors (GEFs). RopGEFs
      show no homology to animal RhoGEFs, and the catalytic mechanism remains elusive.
      GEF-catalysed nucleotide exchange proceeds via transient ternary and stable
      binary complexes. While a number of structural studies have analyzed binary
      nucleotide-free G protein-GEF complexes, very little is known about the ternary
      complexes. Here we report the X-ray structure of the catalytic PRONE domain of
      RopGEF8 from Arabidopsis thaliana, both alone and in a ternary complex with Rop4
      and GDP. The features of the latter complex, a transient intermediate of the
      exchange reaction never directly observed before, suggest a common mechanism of
      catalyzed nucleotide exchange applicable to small G proteins in general.

PMID- 17218275
TI  - L13a blocks 48S assembly: role of a general initiation factor in mRNA-specific
      translational control.
AB  - Transcript-specific translational control restricts macrophage inflammatory gene
      expression. The proinflammatory cytokine interferon-gamma induces phosphorylation
      of ribosomal protein L13a and translocation from the 60S ribosomal subunit to the
      interferon-gamma-activated inhibitor of translation (GAIT) complex. This complex
      binds the 3'UTR of ceruloplasmin mRNA and blocks its translation. Here, we
      elucidate the molecular mechanism underlying repression by L13a. Translation of
      the GAIT element-containing reporter mRNA is sensitive to L13a-mediated silencing
      when driven by internal ribosome entry sites (IRESs) that require initiation
      factor eIF4G, but is resistant to silencing when driven by eIF4F-independent
      IRESs, demonstrating a critical role for eIF4G. Interaction of L13a with eIF4G
      blocks 43S recruitment without suppressing eIF4F complex formation. eIF4G attack,
      e.g., by virus, stress, or caspases, is a well-known mechanism of global
      inhibition of protein synthesis. However, our studies reveal a unique mechanism
      in which targeting of eIF4G by mRNA-bound L13a elicits transcript-specific
      translational repression.

PMID- 17218279
TI  - Altered specificity of a AAA+ protease.
AB  - ClpXP, an ATP-dependent protease, degrades hundreds of different intracellular
      proteins. ClpX chooses substrates by binding peptide tags, typically displayed at
      the N or C terminus of the protein to be degraded. Here, we identify a ClpX
      mutant that displays a 300-fold change in substrate specificity, resulting in
      decreased degradation of ssrA-tagged substrates but improved degradation of
      proteins with other classes of degradation signals. The altered-specificity
      mutation occurs within "RKH" loops, which surround the entrance to the central
      pore of the ClpX hexamer and are highly conserved in the ClpX subfamily of AAA+
      ATPases. These results support a major role for the RKH loops in substrate
      recognition and suggest that ClpX specificity represents an evolutionary
      compromise that has optimized degradation of multiple types of substrates rather
      than any single class.

PMID- 17218278
TI  - An acetylation site in the middle domain of Hsp90 regulates chaperone function.
AB  - Heat-shock protein 90 (Hsp90) chaperones a key subset of signaling proteins and
      is necessary for malignant transformation. Hsp90 is subject to an array of
      posttranslational modifications that affect its function, including acetylation.
      Histone deacetylase (HDAC) inhibitors and knockdown of HDAC6 induce Hsp90
      acetylation and inhibit its activity. However, direct determination of the
      functional consequences of Hsp90 acetylation has awaited mapping of specific
      sites. We now demonstrate that Hsp90 K294 is acetylated. Mutational analysis of
      K294 shows that its acetylation status is a strong determinant of client protein
      and cochaperone binding. In yeast, Hsp90 mutants that cannot be acetylated at
      K294 have reduced viability and chaperone function compared to WT or to mutants
      that mimic constitutive acetylation. These data suggest that
      acetylation/deacetylation of K294 plays an important role in regulating the Hsp90
      chaperone cycle.

PMID- 17218280
TI  - Codon reading by tRNAAla with modified uridine in the wobble position.
AB  - tRNAs reading four-codon families often have a modified uridine, cmo(5)U(34), at
      the wobble position of the anticodon. Here, we examine the effects on the
      decoding mechanism of a cmo(5)U modification in tRNA(1B)(Ala), anticodon
      C(36)G(35)cmo(5)U(34). tRNA(1B)(Ala) reads its cognate codons in a manner that is
      very similar to that of tRNA(Phe). As Ala codons are GC rich and Phe codons AU
      rich, this similarity suggests a uniform decoding mechanism that is independent
      of the GC content of the codon-anticodon duplex or the identity of the tRNA. The
      presence of cmo(5)U at the wobble position of tRNA(1B)(Ala) permits fairly
      efficient reading of non-Watson-Crick and nonwobble bases in the third codon
      position, e.g., the GCC codon. The ribosome accepts the C-cmo(5)U pair as an
      almost-correct base pair, unlike third-position mismatches, which lead to the
      incorporation of incorrect amino acids and are efficiently rejected.

PMID- 17218281
TI  - Why fair tests are needed: a brief history.

PMID- 17218282
TI  - Of studies, syntheses, synopses, summaries, and systems: the "5S" evolution of
      information services for evidence-based healthcare decisions.

PMID- 17218283
TI  - Review: antibiotics are effective for acute purulent rhinitis but are associated
      with increased gastrointestinal side effects.

PMID- 17218284
TI  - Immediate or delayed prescribing of antibiotics reduced duration of symptoms in
      acute infective conjunctivitis.

PMID- 17218285
TI  - Review: exercise improves glycaemic control and reduces plasma triglycerides and
      visceral adipose tissue in type 2 diabetes.

PMID- 17218286
TI  - Review: regular exercise improves quality of life and physical fitness in women
      with breast cancer.

PMID- 17218287
TI  - Review: various interventions prevent or reduce oral mucositis in patients with
      cancer receiving chemotherapy or radiotherapy.

PMID- 17218288
TI  - Review: sparse good quality evidence supports the use of alternative therapies
      for menopausal symptoms.

PMID- 17218289
TI  - Review: sparse evidence supports non-pharmacological interventions for preventing
      wandering in people with dementia.

PMID- 17218290
TI  - Review: a low protein diet delays end stage renal disease or death in chronic
      kidney disease.

PMID- 17218291
TI  - Review: evidence from </=2 low quality studies suggests no difference in surgical
      site infection with or without preoperative hair removal; depilatory cream and
      clipping are better than shaving.

PMID- 17218292
TI  - Review: double gloving during surgery prevents perforations of the inner glove,
      but its effect on infection is unknown.

PMID- 17218293
TI  - Oral decontamination with chlorhexidine reduced ventilator associated pneumonia
      in patients needing mechanical ventilation for >/=48 hours.

PMID- 17218294
TI  - Paraffin ointment or mupirocin ointment did not differ from no ointment under
      moist occlusive dressings on non-contaminated surgical wounds for wound
      infections.

PMID- 17218295
TI  - Review: insufficient evidence exists for any one dressing type (used beneath
      compression) for venous leg ulcer healing.

PMID- 17218296
TI  - Similar proportions of patients developed pressure ulcers on alternating pressure
      overlays and alternating pressure mattresses.

PMID- 17218297
TI  - Alternating pressure mattresses were more cost effective than alternating
      pressure overlays for preventing pressure ulcers.

PMID- 17218298
TI  - Review: good adherence to drug therapy is associated with reduced mortality.

PMID- 17218299
TI  - Review: case management and team changes are particularly effective strategies
      for reducing HbA1c concentrations in type 2 diabetes.

PMID- 17218300
TI  - Audit and feedback and educational outreach did not differ from printed
      educational materials for improving community nursing practice.

PMID- 17218301
TI  - Oral and written information about newborn screening should be concise and given
      to parents by primary prenatal care providers.

PMID- 17218302
TI  - Children as young as 4 years of age with type 1 diabetes showed understanding and
      competence in managing their condition.

PMID- 17218303
TI  - Children of mothers with breast cancer were distressed by hair loss; those >10
      years of age wanted more information about their mother's condition.

PMID- 17218304
TI  - Community nurse behaviours related to patient involvement in decision making
      varied on a continuum of non-involving to involving.

PMID- 17218305
TI  - Patients with cancer used numerical information to calculate the odds and
      mobilise their coping responses.

PMID- 17218306
TI  - Men treated for prostate cancer did not consider urinary, bowel, or sexual
      dysfunction as problems of health.

PMID- 17218307
TI  - The serine/threonine/tyrosine phosphoproteome of the model bacterium Bacillus
      subtilis.
AB  - Protein phosphorylation on serine, threonine, and tyrosine (Ser/Thr/Tyr) is well
      established as a key regulatory posttranslational modification in eukaryotes, but
      little is known about its extent and function in prokaryotes. Although protein
      kinases and phosphatases have been predicted and identified in a variety of
      bacterial species, classical biochemical approaches have so far revealed only a
      few substrate proteins and even fewer phosphorylation sites. Bacillus subtilis is
      a model Gram-positive bacterium in which two-dimensional electrophoresis-based
      studies suggest that the Ser/Thr/Tyr phosphorylation should be present on more
      than a hundred proteins. However, so far only 16 phosphorylation sites on eight
      of its proteins have been determined, mostly in in vitro studies. Here we
      performed a global, gel-free, and site-specific analysis of the B. subtilis
      phosphoproteome using high accuracy mass spectrometry in combination with
      biochemical enrichment of phosphopeptides from digested cell lysates. We
      identified 103 unique phosphopeptides from 78 B. subtilis proteins and determined
      78 phosphorylation sites: 54 on serine, 16 on threonine, and eight on tyrosine.
      Detected phosphoproteins are involved in a wide variety of metabolic processes
      but are enriched in carbohydrate metabolism. We report phosphorylation sites on
      almost all glycolytic and tricarboxylic acid cycle enzymes, several kinases, and
      members of the phosphoenolpyruvate-dependent phosphotransferase system. This
      significantly enlarged number of bacterial proteins known to be phosphorylated on
      Ser/Thr/Tyr residues strongly supports the emerging view that protein
      phosphorylation is a general and fundamental regulatory process, not restricted
      only to eukaryotes, and opens the way for its detailed functional analysis in
      bacteria.

PMID- 17218308
TI  - SRC-p300 coactivator complex is required for thyroid hormone-induced amphibian
      metamorphosis.
AB  - Gene activation by the thyroid hormone (T3) receptor (TR) involves the
      recruitment of specific coactivator complexes to T3-responsive promoters. A large
      number of coactivators for TR have been isolated and characterized in vitro.
      However, their roles and functions in vivo during development have remained
      largely unknown. We have utilized metamorphosis in Xenopus laevis to study the
      role of these coactivators during post-embryonic development. Metamorphosis is
      totally dependent on the thyroid hormone, and TR mediates a vast majority, if not
      all, of the developmental effects of the hormone. We have previously shown that
      TR recruits the coactivator SRC3 (steroid receptor coactivator-3) and that
      coactivator recruitment is essential for metamorphosis. To determine whether SRCs
      are indeed required, we have analyzed the in vivo role of the histone
      acetyltransferase p300/CREB-binding protein (CBP), which was reported to be a
      component of the SRC.coactivator complexes. Chromatin immunoprecipitation
      revealed that p300 is recruited to T3-responsive promoters, implicating a role of
      p300 in TR function. Further, transgenic tadpoles overexpressing a dominant
      negative form of p300, F-dnp300, containing only the SRC-interacting domain,
      displayed arrested or delayed metamorphosis. Molecular analyses of the transgenic
      F-dnp300 animals showed that F-dnp300 was recruited by TR (displacing endogenous
      p300) and inhibited the expression of T3-responsive genes. Our results thus
      suggest that p300 and/or its related CBP is an essential component of the TR
      signaling pathway in vivo and support the notion that p300/CBP and SRC proteins
      are part of the same coactivator complex in vivo during post-embryonic
      development.

PMID- 17218309
TI  - Mapping pathways downstream of sphingosine 1-phosphate subtype 1 by differential
      chemical perturbation and proteomics.
AB  - Sphingosine 1-phosphate subtype 1 (S1P(1)) receptor agonists alter lymphocyte
      trafficking and endothelial barrier integrity in vivo. Among these is the potent,
      non-selective agonist, FTY720-P, whose mechanism of action has been suggested to
      correlate with S1P(1) down-regulation. Discovery of the in vivo active S1P(1)
      selective agonist, SEW2871, has broadened our understanding of minimal
      requirements for S1P(1) function while highlighting differences regarding agonist
      effect on S1P(1) fate, because SEW2871 does not degrade S1P(1). To further
      understand the mechanism of agonist-induced S1P(1) down-regulation, we compared
      signaling and fate of human S1P(1)-green fluorescent protein (GFP) in stable 293
      cells, using AFD-R, a chiral analog of FTY720-P, SEW2871, and S1P. Although all
      agonists acutely internalized S1P(1) to late endosomal vesicles and activated
      GTPgammaS(35) binding and pERK to similar maxima, only AFD-R led to significant
      S1P(1) down-regulation, as shown by GFP immunoprecipitation studies. Down
      regulation was time- and concentration-dependent, was partially blocked by
      proteasomal inhibition and reversed by chloroquine and an antagonist to S1P(1).
      All agonists induced a receptor-associated increase in ubiquitination, with AFD-R
      inducing 3-fold more accumulation than S1P and being 3-4 logs more potent than
      SEW2871. The formation of AFD-R-receptor ubiquitin complex was inhibited by
      antagonist and chloroquine and was enhanced by proteasomal inhibition.
      Identification of proteins by PAGE liquid chromatography-tandem mass spectrometry
      in cells treated with AFD-R confirmed the co-migration of ubiquitin peptides with
      those of S1P(1) and GFP, relative to vehicle alone. These data suggest that the
      hierarchy of ubiquitin recruitment to S1P(1) (AFD-R > S1P > SEW2871) correlates
      with the efficiency of lysosomal receptor degradation and reflects intrinsic
      differences between agonists.

PMID- 17218310
TI  - Toward molecular dissection of PrPC-PrPSc interactions.
AB  - Direct interaction between endogenous cellular prion protein (PrP(C)) and
      misfolded, disease-associated (PrP(Sc)) conformers is a key event in prion
      propagation, which precedes templated conversion of PrP(C) into nascent PrP(Sc)
      and prion infectivity. Although almost none of the molecular details of this
      pivotal process are understood, the persistence of individual prion strains
      suggests that assembly of the prion replicative complex is mechanistically
      precise. To systematically map defined regions of PrP(C) sequence that bind
      tightly to PrP(Sc), we have generated a comprehensive panel of over 45 motif
      grafted antibodies containing overlapping peptide grafts collectively spanning
      PrP residues 19-231. Grafted antibody binding experiments, performed under
      stringent conditions, clearly identified only three distinct and independent high
      affinity PrP(Sc) recognition motifs. The first of these binding motifs lies at
      the very N-terminal region of the mature PrP molecule within PrP-(23-33); the
      second motif lies within PrP-(98-110); and the third is contained within PrP-(136
      158). Mutational analyses of these PrP(Sc)-binding regions revealed that
      reactivity of the 23-33 and 98-110 segments are largely dependent upon the
      presence of multiple positively charged amino acid residues. These studies yield
      new insight into critical peptidic components composing one side of the prion
      replicative interface.

PMID- 17218311
TI  - Neuronal apoptotic signaling pathways probed and intervened by synthetically and
      modularly modified (SMM) chemokines.
AB  - As the main coreceptors for human immunodeficiency virus type 1 (HIV-1) entry,
      CXCR4 and CCR5 play important roles in HIV-associated dementia (HAD). HIV-1
      glycoprotein gp120 contributes to HAD by causing neuronal damage and death,
      either directly by triggering apoptotic pathways or indirectly by stimulating
      glial cells to release neurotoxins. Here, to understand the mechanism of CXCR4 or
      CCR5 signaling in neuronal apoptosis associated with HAD, we have applied
      synthetically and modularly modified (SMM)-chemokine analogs derived from natural
      stromal cell-derived factor-1alpha or viral macrophage inflammatory protein-II as
      chemical probes of the mechanism(s) whereby these SMM-chemokines prevent or
      promote neuronal apoptosis. We show that inherently neurotoxic natural ligands of
      CXCR4, such as stromal cell-derived factor-1alpha or viral macrophage
      inflammatory protein-II, can be modified to protect neurons from apoptosis
      induced by CXCR4-preferring gp120(IIIB), and that the inhibition of CCR5 by
      antagonist SMM-chemokines, unlike neuroprotective CCR5 natural ligands, leads to
      neurotoxicity by activating a p38 mitogen-activated protein kinase (MAPK)
      dependent pathway. Furthermore, we discover distinct signaling pathways activated
      by different chemokine ligands that are either natural agonists or synthetic
      antagonists, thus demonstrating a chemical biology strategy of using chemically
      engineered inhibitors of chemokine receptors to study the signaling mechanism of
      neuronal apoptosis and survival.

PMID- 17218312
TI  - A singular bacteriophytochrome acquired by lateral gene transfer.
AB  - Bacteriophytochromes are phytochrome-like proteins that mediate photosensory
      responses in various bacteria according to their light environment. The genome of
      the photosynthetic and plant-symbiotic Bradyrhizobium sp. strain ORS278 revealed
      the presence of a genomic island acquired by lateral transfer harboring a
      bacteriophytochrome gene, BrBphP3.ORS278, and genes involved in the synthesis of
      phycocyanobilin and gas vesicles. The corresponding protein BrBphP3.ORS278 is
      phylogenetically distant from the other (bacterio)phytochromes described thus far
      and displays a series of unusual properties. It binds phycocyanobilin as a
      chromophore, a unique feature for a bacteriophytochrome. Moreover, its C-terminal
      region is short and displays no homology with any known functional domain. Its
      dark-adapted state absorbs maximally around 610 nm, an unusually short wavelength
      for (bacterio)phytochromes. This form is designated as Po for orange-absorbing
      form. Upon illumination, a photo-reversible switch occurs between the Po form and
      a red (670 nm)-absorbing form (Pr), which rapidly backreacts in the dark. Because
      of this instability, illumination results in a mixture of the Po and Pr states in
      proportions that depend on the intensity. These uncommon features suggest that
      BrBphP3.ORS278 could be fitted to measure light intensity rather than color.

PMID- 17218313
TI  - Polyamine uptake by DUR3 and SAM3 in Saccharomyces cerevisiae.
AB  - It has been reported that GAP1 and AGP2 catalyze the uptake of polyamines
      together with amino acids in Saccharomyces cerevisiae. We have looked for
      polyamine-preferential uptake proteins in S. cerevisiae. DUR3 catalyzed the
      uptake of polyamines together with urea, and SAM3 was found to catalyze the
      uptake of polyamines together with S-adenosylmethionine, glutamic acid, and
      lysine. Polyamine uptake was greatly decreased in both DUR3- and SAM3-deficient
      cells. The K(m) values for putrescine and spermidine of DUR3 were 479 and 21.2
      mum, respectively, and those of SAM3 were 433 and 20.7 mum, respectively.
      Polyamine stimulation of cell growth of a polyamine requiring mutant, which is
      deficient in ornithine decarboxylase, was not influenced by the disruption of
      GAP1 and AGP2, but it was diminished by the disruption of DUR3 and SAM3.
      Furthermore, the polyamine stimulation of cell growth of a polyamine-requiring
      mutant was completely inhibited by the disruption of both DUR3 and SAM3. The
      results indicate that DUR3 and SAM3 are major polyamine uptake proteins in yeast.
      We previously reported that polyamine transport protein kinase 2 regulates
      polyamine transport. It was found that DUR3 (but not SAM3) was activated by
      phosphorylation of Thr(250), Ser(251), and Thr(684) by polyamine transport
      protein kinase 2.

PMID- 17218314
TI  - Export pathway selectivity of Escherichia coli twin arginine translocation signal
      peptides.
AB  - The Escherichia coli genome encodes at least 29 putative signal peptides
      containing a twin arginine motif characteristic of proteins exported via the twin
      arginine translocation (Tat) pathway. Fusions of the putative Tat signal peptides
      plus six to eight amino acids of the mature proteins to three reporter proteins
      (short-lived green fluorescent protein, maltose-binding protein (MBP), and
      alkaline phosphatase) and also data from the cell localization of epitope-tagged
      full-length proteins were employed to determine the ability of the 29 signal
      peptides to direct export through the Tat pathway, through the general secretory
      pathway (Sec), or through both. 27/29 putative signal peptides could export one
      or more reporter proteins through Tat. Of these, 11 signal peptides displayed Tat
      specificity in that they could not direct the export of Sec-only reporter
      proteins. The rest (16/27) were promiscuous and were capable of directing export
      of the appropriate reporter either via Tat (green fluorescent protein, MBP) or
      via Sec (PhoA, MBP). Mutations that conferred a >or=+1 charge to the N terminus
      of the mature protein abolished or drastically reduced routing through the Sec
      pathway without affecting the ability to export via the Tat pathway. These
      experiments demonstrate that the charge of the mature protein N terminus affects
      export promiscuity, independent of the effect of the folding state of the mature
      protein.

PMID- 17218315
TI  - Development of calpain-specific inactivators by screening of positional scanning
      epoxide libraries.
AB  - Calpains are calcium-dependent proteases that are required for numerous
      intracellular processes but also play an important role in the development of
      pathologies such as ischemic injury and neurodegeneration. Many current small
      molecule calpain inhibitors also inhibit other cysteine proteases, including
      cathepsins, and need improved selectivity. The specificity of inhibition of
      several calpains and papain was profiled using synthetic positional scanning
      libraries of epoxide-based compounds that target the active-site cysteine. These
      peptidomimetic libraries probe the P4, P3, and P2 positions, display (S,S)- or
      (R,R)-epoxide stereochemistries, and incorporate both natural and non-natural
      amino acids. To facilitate library screening, an SDS-PAGE assay that measures the
      extent of hydrolysis of an inactive recombinant m-calpain was developed.
      Individual epoxide inhibitors were synthesized guided by calpain-specific
      preferences observed from the profiles and tested for inhibition against calpain.
      The most potent compounds were assayed for specificity against cathepsins B, L,
      and K. Several compounds demonstrated high inhibition specificity for calpains
      over cathepsins. The best of these inhibitors, WRH(R,R), irreversibly inactivates
      m- and mu-calpain rapidly (k(2)/K(i) = 131,000 and 16,500 m(-1) s(-1),
      respectively) but behaves exclusively as a reversible and less potent inhibitor
      toward the cathepsins. X-ray crystallography of the proteolytic core of rat mu
      calpain inactivated by the epoxide compounds WR gamma-cyano-alpha-aminobutyric
      acid (S,S) and WR allylglycine (R,R) reveals that the stereochemistry of the
      epoxide influences positioning and orientation of the P2 residue, facilitating
      alternate interactions within the S2 pocket. Moreover, the WR gamma-cyano-alpha
      aminobutyric acid (S,S)-complexed structure defines a novel hydrogen-bonding site
      within the S2 pocket of calpains.

PMID- 17218316
TI  - TRPA1 is differentially modulated by the amphipathic molecules trinitrophenol and
      chlorpromazine.
AB  - TRPA1, a poorly selective Ca(2+)-permeable cation channel, is expressed in
      peripheral sensory neurons, where it is considered to contribute to a variety of
      sensory processes such as the detection of painful stimuli. Furthermore, TRPA1
      was also identified in hair cells of the inner ear, but its involvement in
      sensing mechanical forces is still being controversially discussed. Amphipathic
      molecules such as trinitrophenol and chlorpromazine have been shown to provide
      useful tools to study mechanosensitive channels. Depending on their charge, they
      partition in the inner or outer sheets of the lipid bilayer, causing a curvature
      of the membrane, which has been demonstrated to activate or inhibit
      mechanosensitive ion channels. In the present study, we investigated the effect
      of these molecules on TRPA1 gating. TRPA1 was robustly activated by the anionic
      amphipathic molecule trinitrophenol. The whole-cell and single channel properties
      resemble those previously described for TRPA1. Moreover, we could show that the
      toxin GsMTx-4 acts on TRPA1. In addition to its recently described role as an
      inhibitor of stretch-activated ion channels, it serves as a potent activator of
      TRPA1 channels. On the other hand, the positively charged drug chlorpromazine
      modulates activated TRPA1 currents in a voltage-dependent way. The exposure of
      activated TRPA1 channels to chlorpromazine led to a block at positive potentials
      and an increased open probability at negative potentials. The variability in the
      shape of the I-V curve gives a first indication that native mechanically
      activated TRPA1 currents must not necessarily exhibit the same biophysical
      properties as ligand-activated TRPA1 currents.

PMID- 17218317
TI  - Reaction of Mycobacterium tuberculosis truncated hemoglobin O with hydrogen
      peroxide: evidence for peroxidatic activity and formation of protein-based
      radicals.
AB  - In this work, we investigated the reaction of ferric Mycobacterium tuberculosis
      truncated hemoglobin O (trHbO) with hydrogen peroxide. Stopped-flow
      spectrophotometric experiments under single turnover conditions showed that trHbO
      reacts with H(2)O(2) to give transient intermediate(s), among which is an
      oxyferryl heme, different from a typical peroxidase Compound I (oxyferryl heme pi
      cation radical). EPR spectroscopy indicated evidence for both tryptophanyl and
      tyrosyl radicals, whereas redox titrations demonstrated that the peroxide-treated
      protein product retains 2 oxidizing eq. We propose that Compound I formed
      transiently is reduced with concomitant oxidation of Trp(G8) to give the detected
      oxoferryl heme and a radical on Trp(G8) (detected by EPR of the trHbO Tyr(CD1)Phe
      mutant). In the wild-type protein, the Trp(G8) radical is in turn reduced rapidly
      by Tyr(CD1). In a second cycle, Trp(G8) may be reoxidized by the ferryl heme to
      yield ferric heme and two protein radicals. In turn, these migrate to form
      tyrosyl radicals on Tyr(55) and Tyr(115), which lead, in the absence of a
      reducing substrate, to oligomerization of the protein. Steady-state kinetics in
      the presence of H(2)O(2) and the one-electron donor 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) indicated that trHbO has peroxidase
      activity, in accord with the presence of typical peroxidase intermediates. These
      findings suggest an oxidation/reduction function for trHbO and, by analogy, for
      other Group II trHbs.

PMID- 17218318
TI  - Membrane curvature alters the activation kinetics of the epithelial Na+/H+
      exchanger, NHE3.
AB  - The epithelial Na(+)/H(+) exchanger, NHE3, was found to activate slowly following
      an acute cytosolic acidification. The sigmoidal course of activation could not be
      explained by the conventional two-state model, which postulates that activation
      results from protonation of an allosteric modifier site. Instead, mathematical
      modeling predicted the existence of three distinct states of the exchanger: two
      different inactive states plus an active form. The interconversion of the
      inactive states is rapid and dependent on pH, whereas the conversion between the
      second inactive state and the active conformation is slow and pH-independent but
      subject to regulation by other stimuli. Accordingly, exposure of epithelial cells
      to hypoosmolar solutions activated NHE3 by accelerating this latter transition.
      The number of surface-exposed exchangers and their association with the
      cytoskeleton were not affected by hypoosmolarity. Instead, NHE3 is activated by
      the membrane deformation, a result of cell swelling. This was suggested by the
      stimulatory effects of amphiphiles that induce a comparable positive (convex)
      deformation of the membrane. We conclude that NHE3 exists in multiple states and
      that different physiological parameters control the transitions between them.

PMID- 17218319
TI  - PU.1 activates transcription of SHP-1 gene in hematopoietic cells.
AB  - Protein-tyrosine phosphatase SHP-1 is the key negative regulator of numerous
      signaling pathways. SHP-1 is expressed in the hematopietic and epithelial cells
      as two structurally similar mRNA transcripts controlled by two different
      promoters designated P2 and P1, respectively. Whereas the transcriptional
      regulation of the SHP-1 gene P1 promoter has been partially elucidated, the
      structure and functional control of the P2 promoter remain unknown despite the
      critical role played by SHP-1 in the normal and malignant lymphoid and other
      hematopoetic cells. Using luciferase reporter assays with the set of constructs
      that contained a gradually truncated intron 1 of the SHP-1 gene, we identified
      the minimal (<120 bp) fragment that is able to fully activate expression of the
      reporter gene. Furthermore, we found that PU.1 (a member of the Ets transcription
      factor family that plays a crucial role in differentiation and function of the
      lymphoid and myeloid cells) binds to the identified P2 promoter both in vitro and
      in vivo. PU.1 also activates the promoter in the sequence specific manner and is
      critical for its expression as evidenced by the profound supression of the SHP-1
      gene transcription upon the siRNA-mediated depletion of PU.1. These findings
      provide an insight into the structure of the hematopoietic cell-specific P2
      promoter of the SHP-1 gene and identify PU.1 as the transcriptional activator of
      the P2 promoter.

PMID- 17218320
TI  - Chromatin remodeling of interleukin-17 (IL-17)-IL-17F cytokine gene locus during
      inflammatory helper T cell differentiation.
AB  - During differentiation of naive CD4+ helper T (TH) cells into effector cells,
      specific cytokine gene loci undergo extensive changes in chromatin modification.
      A novel lineage of TH cells that is regulated by transforming growth factor-beta
      (TGFbeta) and interleukin-6 (IL-6) has been identified recently as promoting
      tissue inflammation. These inflammatory TH (THi) cells, also called TH17 or TH(IL
      17), produce IL-17 and IL-17F, two highly homologous cytokines that have genes
      located in the same chromosomal region. Here, using chromatin immunoprecipitation
      techniques, we have demonstrated that similar to the regulation in TH1 and TH2
      cell lineages, polarization of THi cells was accompanied by selective chromatin
      remodeling events. Histone H3 acetylation and Lys-4 tri-methylation were
      specifically associated with IL-17 and IL-17F gene promoters in THi lineage. At
      an early stage of T cell activation, histone acetylation on these promoters was
      greatly promoted by a combination of TGFbeta and IL-6, suggesting their
      synergistic role in initiating chromatin accessibility for transcription factors.
      Furthermore, we identified multiple noncoding sequences within the IL-17-IL-17F
      locus conserved across species. These elements were also associated with
      hyperacetylated histone 3 in a lineage-specific manner and may thus serve as
      potential regulatory regions. In summary, our results demonstrate for the first
      time that THi cell differentiation is associated with epigenetic changes in the
      IL-17-IL-17F locus, which suggests novel mechanisms in T cell functional
      regulation.

PMID- 17218321
TI  - Selective control of skeletal muscle differentiation by Akt1.
AB  - The phosphatidylinositol 3-kinase-Akt pathway plays a central role in growth,
      development, and metabolism in both normal and neoplastic cells. In skeletal
      muscle, Akt has been implicated in regulating regeneration and hypertrophy and in
      counteracting atrophy. Here we provide evidence that Akt1 and not Akt2 is
      essential for muscle differentiation. Using a robust model of MyoD-mediated
      muscle development, in which dominant-negative Akt blocked differentiation, we
      show that targeted loss of Akt1 was equally inhibitory. Selective elimination of
      Akt1 had no effect on myoblast viability or proliferation but prevented
      differentiation by impairing the transcriptional actions of MyoD. In contrast,
      knockdown of Akt2 had no effect on myoblast survival or differentiation and
      minimally inhibited MyoD-regulated transcription. Our results define isoform
      specific Akt-regulated signaling pathways in muscle cells that act through Akt1
      to sustain muscle gene activation and promote differentiation.

PMID- 17218322
TI  - Commentary: Comprehensive health assessments for adults with intellectual
      disabilities.

PMID- 17218323
TI  - Commentary: Should I blame mom or dad? Identifying the relative contribution of
      each parent's body size to that of their offspring.

PMID- 17218324
TI  - Commentary: Could biomass fuel smoke cause anaemia and stunting in early
      childhood?

PMID- 17218325
TI  - Modelling the impact on Hepatitis C transmission of reducing syringe sharing:
      London case study.
AB  - BACKGROUND: Hepatitis C virus (HCV) prevalence and incidence among injecting drug
      users (IDUs) has increased in London and rest of UK. To inform public health
      action, mathematical modelling is used to explore the possible impact of
      strategies to decrease syringe sharing. METHODS: A mathematical model was
      developed to simulate HCV transmission amongst IDUs in London. Because of
      parameter uncertainty, numerical search algorithms were used to obtain different
      model fits to HCV seroprevalence data from London for 2002-03. These simulations
      were used to explore the likely impact of HCV prevention activities that reduce
      syringe sharing amongst all IDUs, IDUs that have injected for greater than one
      year, or IDUs with lower or higher frequencies of syringe sharing. RESULTS: Key
      differences between model fits centred on how they simulated the high HCV
      incidence amongst new injectors, either through assuming increased HCV
      infectivity during acute infection, a large sub-group of high frequency syringe
      sharers, or increased sharing among new IDUs. Despite parameter uncertainty, the
      model projections suggest that modest reductions in syringe sharing frequency
      (<25%) will reduce the HCV seroprevalence in newly initiated IDUs (injecting less
      than four years) but much larger and sustained reductions (>50%) are required to
      reduce the HCV seroprevalence in long-term IDUs (injecting more than 8 years).
      Critically the model also suggested that large reductions in HCV seroprevalence
      will be achieved only if interventions target all IDUs and reach IDUs within 12
      months of injecting. DISCUSSION: Public health interventions must reduce syringe
      sharing amongst all IDUs, including newly initiated IDUs, and be sustained for
      many years to reduce HCV infection. More accurate data on key behavioural
      (sharing frequency) and biological (percentage of infected IDUs that clear
      infection) parameters is required to improve model projections.

PMID- 17218326
TI  - Effects of a comprehensive health assessment programme for Australian adults with
      intellectual disability: a cluster randomized trial.
AB  - BACKGROUND: People with intellectual disability constitute approximately 2% of
      the population. They die prematurely, and often have a number of unrecognized or
      poorly managed medical conditions as well as inadequate health promotion and
      disease prevention. METHODS: A cluster randomized controlled trial with matched
      pairs was carried out. The participants were adults with intellectual disability
      (n = 453 in 34 clusters). The intervention was a health assessment programme to
      enhance interactions between the adult with intellectual disability, their carer
      and their general practitioner (GP). It prompted the systematic gathering of a
      health history and, subsequently, access to a GP for a guided health review and
      development of a health action plan. It also provided information about the
      health of adults with intellectual disability. Follow-up was for 1 year post
      intervention, with outcomes extracted from GPs' clinical records. RESULTS:
      Increased health promotion, disease prevention and case-finding activity was
      found in the intervention group. Compared with the control group there was a 6.6
      fold increase in detection of vision impairment (95% confidence interval 1.9-40);
      a 30-fold increase in hearing testing (4.0-230); an increase in immunization
      updates [tetanus/diphtheria a 9-fold increase (4.2-19)], and improvements in
      women's health screening [Papanicolau smears were eight times more common (1.8
      35)]. The intervention increased detection of new disease by 1.6 times (0.9-2.8).
      CONCLUSIONS: The Comprehensive Health Assessment Program (CHAP) produced a
      substantial increase in GPs' attention to the health needs of adults with
      intellectual disability with concomitantly more disease detection. The
      presumption that these will yield longer-term health benefits, while suggestive,
      remains unexamined.

PMID- 17218327
TI  - A prospective double blind placebo-controlled randomized trial of ultrasound in
      the physiotherapy treatment of shoulder pain.
AB  - OBJECTIVE: To compare the effectiveness of manual therapy and ultrasound (US)
      with manual therapy and placebo ultrasound (placebo US) in the treatment of new
      episodes of unilateral shoulder pain referred for physiotherapy. METHODS: In a
      multicentre, double blind, placebo-controlled randomized trial, participants were
      recruited with a clinical diagnosis of unilateral shoulder pain from nine primary
      care physiotherapy departments in Birmingham, UK. Recruitment took place from
      January 1999 to September 2001. Participants were 18 yrs old and above.
      Participants all received advice and home exercises and were randomized to
      additionally receive manual therapy plus US or manual therapy plus placebo US.
      The primary outcome measure was the Shoulder Disability Questionnaire (SDQ-UK).
      Outcomes were assessed at baseline, 2 weeks, 6 weeks and 6 months. Analysis was
      by intention to treat. RESULTS: A total of 221 participants (mean age 56 yrs)
      were recruited. 113 participants were randomized to US and 108 to placebo US.
      There was 76% follow up at 6 weeks and 71% at 6 months. The mean (95% CI)
      reduction in SDQ scores at 6 weeks was 17 points (13-26) for US and 13 points (9
      17) for placebo US (P = 0.06). There were no statistically significant
      differences at the 5% level in mean changes between groups at any of the time
      points. CONCLUSIONS: The addition of US was not superior to placebo US when used
      as part of a package of physiotherapy in the short-term management of shoulder
      pain. This has important implications for physiotherapy practice.

PMID- 17218328
TI  - Interleukin-1beta induced activation of nuclear factor-kappab can be inhibited by
      novel pharmacological agents in osteoarthritis.
AB  - OBJECTIVES: To investigate the importance of activation of the transcription
      factor, nuclear factor-kappaB (NF-kappaB) by interleukin-1beta (IL-1beta) and
      tumour necrosis factor-alpha (TNF-alpha) in the pathogenesis of osteoarthritis
      (OA) and assess its suitability as a target for therapy by determining its role
      in the induction of the cytokine IL-6 and the degenerative enzymes, matrix
      metalloproteinase (MMP)-1 and MMP-3 in vitro. METHODS: Three distinct cellular
      models, derived from primary OA tissue, were employed, namely, fibroblast-like
      synoviocytes (OA-SF); co-cultures containing phenotypic macrophage-like and
      fibroblast-like cells (OA-COCUL); and primary OA synovial tissue explants (OA
      EXP). These were treated with specific inhibitors of IL-1beta, TNF-alpha and NF
      kappaB to assess their differential role in the production of pathologically
      relevant mediators, specifically IL-6, MMP-1, MMP-3 and the tissue inhibitor of
      metalloproteinases-1 (TIMP-1), which were quantified by enzyme-linked
      immunosorbent assay. RESULTS: Inhibition of NF-kappaB by a novel agent, RO100 at
      a dose of 0.1 microM, exerted significant (P < 0.05) repression of IL-6, MMP-1
      and MMP-3 production in OA-SF. Notably, neither TIMP-1 production nor cell
      viability was significantly affected at the dose tested. These data were
      reproduced in OA-EXP, which might be considered as having greater physiological
      relevance. Interestingly, comparable efficacy was noted using IL-1beta and TNF
      alpha neutralizing antibodies in OA-COCUL. CONCLUSIONS: We have demonstrated that
      a novel pharmacological inhibitor of NF-kappaB, RO100 inhibits pathological
      mediators of OA progression with equivalent efficacy as established IL-1beta and
      TNF-alpha neutralizing strategies. Our findings highlight a potential for
      developing NF-kappaB targeted therapeutics for positively regulating disease
      activity and improving clinical outcome in OA.

PMID- 17218329
TI  - Mycophenolate mofetil for maintenance of remission in idiopathic retroperitoneal
      fibrosis.

PMID- 17218330
TI  - A calmodulin-binding mitogen-activated protein kinase phosphatase is induced by
      wounding and regulates the activities of stress-related mitogen-activated protein
      kinases in rice.
AB  - The mitogen-activated protein kinase (MAPK) phosphatases (MKPs) are negative
      regulators of MAPKs. In dicotyledons such as Arabidopsis and tobacco, MKPs have
      been shown to play pivotal roles in abiotic stress responses, hormone responses
      and microtubule organization. However, little is known about the role of MKPs in
      monocotyledons such as rice. Database searches identified five putative MKPs in
      rice. We investigated their expression in response to wounding, and found that
      the expression of OsMKP1 is rapidly induced by wounding. In this study, we
      functionally characterized the involvement of OsMKP1 in wound responses. The
      deduced amino acid sequence of OsMKP1 shows strong similarity to Arabidopsis
      AtMKP1 and tobacco NtMKP1. Moreover, OsMKP1 bound calmodulin in a manner similar
      to NtMKP1. To determine the biological function of OsMKP1, we obtained osmkp1, a
      loss-of-function mutant, in which retrotransposon Tos17 was inserted in the
      second exon of OsMKP1. Unlike the Arabidopsis atmkp1 loss-of-function mutant,
      which shows no abnormal phenotype without stimuli, osmkp1 showed a semi-dwarf
      phenotype. Exogenous supply of neither gibberellin nor brassinosteroid
      complemented the semi-dwarf phenotype of osmkp1. Activities of two stress
      responsive MAPKs, OsMPK3 and OsMPK6, in osmkp1 were higher than those in the wild
      type both before and after wounding. Microarray analysis identified 13 up
      regulated and eight down-regulated genes in osmkp1. Among the up-regulated genes,
      the expression of five genes showed clear responses to wounding, indicating that
      wound responses are constitutively activated in osmkp1. These results suggest
      that OsMKP1 is involved in the negative regulation of rice wound responses.

PMID- 17218331
TI  - Smoking and injury in Royal Marines' training.
AB  - BACKGROUND: Training for the Royal Marines (RMs) is considered to be one of the
      most arduous military training regimes in the world. Approximately 16% of the
      annual intake of recruits suffer an injury. Smoking has been found to be a
      predisposition to injury. OBJECTIVE: To examine the relationship between
      recruits' smoking status on entry to training and subsequent incidence of injury.
      METHOD: Retrospective, longitudinal analysis of 1 year's intake of RM recruits at
      Commando Training Centre Royal Marines. RESULTS: A significantly greater
      proportion of RM recruits who were smokers on entry to training experienced a
      physical injury during the course than their non-smoking counterparts (chi-square
      = 8.15, P < 0.01). A recruit who smoked on entry to training was almost twice as
      likely to acquire an injury during training [relative risk = 1.7 (95% CI = 1.2
      2.8)]. CONCLUSION: Smoking status of RM recruits in training was significantly
      associated with injury.

PMID- 17218332
TI  - Lack of cardiac anomalies in children with NPHS2 mutations.

PMID- 17218333
TI  - Statistical validation of the root-mean-square-distance, a measure of protein
      structural proximity.
AB  - Despite its well-documented limitations, the root-mean-square-distance (rmsd)
      between pairs of equivalent atoms is routinely used to monitor the degree of
      similarity between two optimally superposed protein three-dimensional structures.
      A robust method for assessing the statistical significance of the difference
      between two rmsd values is presented here. It is based on the comparison of two
      protein structures through the correlation coefficient between equivalent inter
      atomic distances and the subsequent application of the Fisher transformation that
      allows one to estimate the probability of identity between two correlation
      coefficient values. The relationship between the rmsd and Fisher correlation
      coefficient allows then to estimate the statistical significance of the
      difference between two rmsd values. Such a procedure is exemplified with the
      analysis of the possible classifications of the immunoglobulin-like domains of
      filamin and is compared to related estimations of structural similarity. The
      possibility to estimate the probability of the difference between two rmsd values
      can be used to optimize the protein structural classifications and comparisons,
      independent of the procedure used to derive the rmsds.

PMID- 17218334
TI  - Design and facile production of recombinant resilin-like polypeptides: gene
      construction and a rapid protein purification method.
AB  - Resilin is an elastic protein found in specialized regions of the cuticle of
      insects, which displays unique resilience and fatigue lifetime properties. As is
      the case with many elastomeric proteins, including elastin, gliadin and spider
      silks, resilin contains distinct repetitive domains that appear to confer elastic
      properties to the protein. Recent work within our laboratory has demonstrated
      that cloning and expression of exon 1 of the Drosophila melanogaster CG15920
      gene, encoding a putative resilin-like protein, results in a recombinant protein
      that can be photochemically crosslinked to form a highly resilient, elastic
      biomaterial (Rec1 resilin). The current study describes a recursive cloning
      strategy for generating synthetic genes encoding multiple copies of consensus
      polypeptides, based on the repetitive domains within resilin-like genes from D.
      melanogaster and Anopheles gambiae. A simple non-chromatographic purification
      method that can be applied to these synthetic proteins and Rec1 is also reported.
      These methods for the design and purification of resilin-like periodic
      polypeptides will facilitate the future investigation of structural and
      functional properties of resilin, and the development of novel highly resilient
      biomaterials.

PMID- 17218335
TI  - New insights into the role of the thumb-like loop in GH-11 xylanases.
AB  - GH-11 xylanases are highly specific and possess a thumb-shaped loop, a unique
      structure among enzymes with a jelly-roll scaffold. To investigate this
      structure, in vitro mutagenesis was performed on a GH-11 xylanase (Tx-Xyl) from
      Thermobacillus xylanilyticus. Targets were the conserved amino acids Pro(114)
      Ser(115)-Ile(116) that are located at the thumb's tip and Thr(121) and Tyr(111),
      linker residues that connect the thumb to the main enzyme scaffold. Site
      saturation mutagenesis provided an active variant that possesses a new triplet
      (Pro(114)-Gly(115)-Cys(116)), not found in naturally occurring GH-11 xylanases.
      The k(cat) value for xylan hydrolysis catalysed by this mutant was increased by
      20%. Re-positioning of the thumb through the deletion of the linker residues
      produced different effects. As predicted by in silico analyses, deletion of
      Thr(121) had drastic consequences on activity, whereas deletion of Tyr(111) only
      affected (4-fold decrease) k(cat). Finally, deletion mutagenesis was used to
      create a thumbless variant that was almost catalytically inactive. Fluorescence
      titration with xylotetraose and xylopentaose revealed that this thumb-deleted
      xylanase retained the ability to bind substrates. This binding was comparable to
      that of the wild-type enzyme. Additionally, unlike wild-type Tx-Xyl, the thumb
      deleted xylanase efficiently bound cellotetraose, although no cellulose
      hydrolysing activity was detected. Overall, these data show that the thumb is a
      key determinant for substrate selection and support previous data that suggest
      that it plays a role in the catalytic process.

PMID- 17218336
TI  - In vivo selection for the enhancement of Thermotoga maritima exopolygalacturonase
      activity at neutral pH and low temperature.
AB  - The aim of this study was to develop an Escherichia coli-based metabolic
      selection system for the uncovering of new oligogalacturonate-active enzymes.
      Based on the expression of the specific permease TogMNAB, this system enabled the
      entry of oligogalacturonates into the cytoplasm of E. coli thus providing a
      modified strain usable for this purpose. This tool was used for the metabolic
      selection of Thermotoga maritima exopolygalacturonase (TmGalU) mutants enabling
      the uptake of sodium trigalacturonate as the sole carbon source by the bacterium.
      In only one round of error-prone PCR and selection, mutants of TmGalU with a 4
      fold increased turnover at pH 7.0 and 2-fold more active at 37 degrees C than
      wild-type enzyme were isolated. These results show the versatility of this strain
      for the evolution of oligogalacturonate-active enzymes.

PMID- 17218337
TI  - Bacteriophage Mu C protein is a new member of unusual leucine zipper-HTH class of
      proteins.
AB  - Transcription activator protein C of bacteriophage Mu activates transcription of
      the late genes, including mom, during the lytic cycle of the phage. C binding to
      its site leads to the alteration in DNA topology of the promoter elements
      resulting in RNA polymerase (RNAP) recruitment. At the next step, the
      transactivator enhances promoter clearance of RNAP from P(mom). The C protein
      binds DNA with a very high affinity using a carboxyl-terminal helix turn helix
      (HTH) motif which has similarity with the HTH from paired domain of Drosophila
      prd protein. Previous studies established that the protein is dimeric in free and
      DNA bound forms. We describe now the unique dimerization interface of the
      protein. Two heptad repeats of hydrophobic amino acids found in the protein were
      considered to be the candidates for dimerization region. Site-directed mutational
      analysis revealed that the amino-terminal coiled coil region is not the
      dimerization determinant. In contrast, similar mutagenesis studies indicated a
      role for the leucine zipper motif, located in the middle region of the protein,
      in dimerization. Mixed oligomerization assays confirmed the importance of leucine
      zipper in C dimer formation establishing the presence of an uncommon zipper-HTH
      domain in the transactivator.

PMID- 17218339
TI  - Stem-righting mechanism in gymnosperm trees deduced from limitations in
      compression wood development.
AB  - BACKGROUND AND AIMS: In response to inclination stimuli, gymnosperm trees undergo
      corrective growth during which compression wood develops on the lower side of the
      inclined stem. High compressive growth stress is generated in the compression
      wood region and is an important factor in righting the stem. The aims of the
      study were to elucidate how the generation of compressive growth stress in the
      compression wood region is involved in the righting response and thus to
      determine a righting mechanism for tree saplings. METHODS: Cryptomeria japonica
      saplings were grown at inclinations of 0 degrees (vertical) to 50 degrees. At
      each inclination angle, the growth stress on the lower side of the inclined stem
      was investigated, together with the degree of compression-wood development such
      as the width of the current growth layer and lignin content, and the upward
      bending moment. KEY RESULTS: Growth stress, the degree of compression wood
      development, and the upward moment grew as the stem inclination angle increased
      from 0 to 30 degrees, but did not rise further at inclinations > 30 degrees.
      CONCLUSIONS: The results suggest the following righting mechanism for gymnosperm
      saplings. As the stem inclination is elevated from 0 to 30 degrees, the degree of
      compression wood development increases to force the sapling back to its original
      orientation; at inclinations > 30 degrees, the maximum degree of compression wood
      is formed and additional time is needed for the stem to reorient itself.

PMID- 17218338
TI  - Multiple urban and asthma-related risks and their association with asthma
      morbidity in children.
AB  - OBJECTIVE: To determine whether a multi-dimensional cumulative risk index (CRI)
      is a stronger predictor of asthma morbidity in urban, school-aged children with
      asthma, than poverty or severity alone. METHODS: A total of 163 children with
      asthma, ages 7-15 years (42% female; 69% ethnic minority) and their primary
      caregivers completed interview-based questionnaires, focusing on potential
      cultural, contextual, and asthma-specific risks that can impact asthma morbidity.
      RESULTS: Higher levels of cumulative risks were associated with more asthma
      morbidity, after controlling for poverty level or asthma severity. Analyses by
      ethnic group and subgroup also supported the relationship between the CRI and
      specific indices of asthma morbidity. CONCLUSIONS: This study demonstrates the
      utility of multiple-dimensional risk models for predicting variations in asthma
      morbidity in urban children. Research efforts with urban families who have
      children with asthma need to consider the context of urban poverty as it relates
      to children's cultural backgrounds and specific asthma outcomes.

PMID- 17218340
TI  - Phylogenetic origins of the Himalayan endemic Dolomiaea, Diplazoptilon and
      Xanthopappus (Asteraceae: Cardueae) based on three DNA regions.
AB  - BACKGROUND AND AIMS: It is an enduring question as to the mechanisms leading to
      the high diversity and the processes producing endemics with unusual morphologies
      in the Himalayan alpine region. In the present study, the phylogenetic
      relationships and origins of three such endemic genera were analysed, Dolomiaea,
      Diplazoptilon and Xanthopappus, all in the tribe Cardueae of Asteraceae. METHODS:
      The nuclear rDNA internal transcribed spacer (ITS) and plastid trnL-F and psbA
      trnH regions of these three genera were sequenced. The same regions for other
      related genera in Cardueae were also sequenced or downloaded from GenBank.
      Phylogenetic trees were constructed from individual and combined data sets of the
      three types of sequences using maximum parsimony, maximum likelihood and Bayesian
      analyses. KEY RESULTS: The phylogenetic tree obtained allowed earlier hypotheses
      concerning the relationships of these three endemic genera based on gross
      morphology to be rejected. Frolovia and Saussurea costus were deeply nested
      within Dolomiaea, and the strong statistical support for the Dolomiaea-Frolovia
      clade suggested that circumscription of Dolomiaea should be more broadly
      redefined. Diplazoptilon was resolved as sister to Himalaiella, and these two
      together are sister to Lipschitziella. The clade comprising these three genera is
      sister to Jurinea, and together these four genera are sister to the Dolomiaea
      Frolovia clade. Xanthopappus, previously hypothesized to be closely related to
      Carduus, was found to be nested within a well-supported but not fully resolved
      Onopordum group with Alfredia, Ancathia, Lamyropappus, Olgaea, Synurus and
      Syreitschikovia, rather than the Carduus group. The crude dating based on ITS
      sequence divergence revealed that the divergence time of Dolomiaea-Frolovia from
      its sister group probably occurred 13.6-12.2 million years ago (Ma), and the
      divergence times of the other two genera, Xanthopappus and Diplazoptilon, from
      their close relatives around 5.7-4.7 Ma and 2.0-1.6 Ma, respectively.
      CONCLUSIONS: The findings provide an improved understanding of the intergeneric
      relationships in Cardueae. The crude calibration of lineages indicates that the
      uplifts of the Qiinghai-Tibetan Plateau since the Miocene might have served as a
      continuous stimulus for the production of these morphologically aberrant endemic
      elements of the Himalayan flora.

PMID- 17218341
TI  - Elevated atmospheric CO2 and strain of rhizobium alter freezing tolerance and
      cold-induced molecular changes in alfalfa (Medicago sativa).
AB  - BACKGROUND AND AIMS: The objective of the study was to assess the impact of
      elevated CO2 in interaction with rhizobial strains on freezing tolerance and cold
      induced molecular changes in alfalfa. METHODS: Alfalfa inoculated with two
      different strains of rhizobium (A2 and NRG34) was grown and cold acclimated (2
      weeks at 2 degrees C) under either 400 (ambient) or 800 micromol mol(-1)
      (elevated) CO2. KEY RESULTS: Plants acclimated under 400 micromol mol(-1) CO2
      were more freezing tolerant than those maintained under 800 micromol mol(-1).
      Cryoprotective sugars typically linked with the acquisition of freezing tolerance
      such as sucrose, stachyose and raffinose increased in roots in response to low
      temperature but did not differ between CO2 treatments. Similarly high CO2 did not
      alter the expression of many cold-regulated (COR) genes although it significantly
      increased the level of transcripts encoding a COR gene homologous to
      glyceraldehyde-3-phosphate-dehydrogenase (GAPDH). A significant effect of
      rhizobial strain was observed on both freezing tolerance and gene expression.
      Plants of alfalfa inoculated with strain A2 were more freezing tolerant than
      those inoculated with strain NRG34. Transcripts of COR genes homologous to a
      pathogenesis-related protein (PR-10) and to a nuclear-targeted protein were
      markedly enhanced in roots of alfalfa inoculated with strain A2 as compared with
      strain NRG34. Transcripts encoding the vegetative storage proteins (VSPs) beta
      amylase and chitinase were more abundant in roots of non-acclimated plants
      inoculated with strain NRG34 than with strain A2. CONCLUSIONS: Taken together,
      the results suggest that elevated CO2 stimulates plant growth and reduces
      freezing tolerance. The acquisition of cold tolerance is also influenced by the
      rhizobial strain, as indicated by lower levels of expression of COR genes and
      sustained accumulation of VSP-encoding transcripts in alfalfa inoculated with
      strain NRG34 as compared with strain A2.

PMID- 17218342
TI  - Distribution of flower morphs, ploidy level and sexual reproduction of the
      invasive weed Oxalis pes-caprae in the western area of the Mediterranean region.
AB  - BACKGROUND AND AIMS: Oxalis pes-caprae is a widespread invasive weed in regions
      with a Mediterranean climate. In its native habitat (southern Africa) this
      species has been reported as heterostylous with trimorphic flowers and a self-
      and morph-incompatible reproductive system. In most of the areas invaded, only a
      pentaploid short-styled morphotype that reproduces mainly asexually by bulbils is
      reported, but this has only been confirmed empirically. This study aims to
      analyse the floral morph proportions in a wide distribution area, test the sexual
      female success, and explain the causes of low sexual reproduction of this species
      in the western area of the Mediterranean Basin. METHODS: Fifty-five populations
      of O. pes-caprae were sampled in the Iberian Peninsula and Morocco to evaluate
      the floral morph ratio and individual fruit set. In plants from a dimorphic
      population, hand-pollination experiments were performed to evaluate the effect of
      the pollen source on pollen tube growth through the style. The ploidy level and
      genome size of individuals of each floral morph were analysed using flow
      cytometry. KEY RESULTS: From the populations studied 89.1 % were monomorphic,
      with most of them containing the short-styled (SS) floral morph, and 10.9 % were
      dimorphic containing long-styled (LS) and SS morphs. In some of these, isoplethy
      was verified but no fruit production was observed in any population. A sterile
      form was also recorded in several populations. Hand-pollination experiments
      revealed that pollen grains germinated over recipient stigmas. In intermorph
      crossings, pollen tubes were able to develop and fruit initiation was observed in
      some cases, while in intramorph pollinations, pollen tube development was
      sporadic and no fruit initiation was observed. All individuals within each floral
      form presented the same DNA ploidy level: SS plants were pentaploid and LS and
      the sterile form were tetraploid. CONCLUSIONS: The low or null sexual
      reproduction success of this species in the area of invasion studied seems
      related with the high frequency of monomorphic populations, the unequal
      proportion of floral morphs in dimorphic populations and the presence of
      different ploidy levels between SS and LS morphs. The discovery of the occurrence
      of an LS floral morph and a sterile form, whose invading capacity in these areas
      is as yet unknown, will be valuable information for management programmes.

PMID- 17218343
TI  - An overview of the biology of the desiccation-tolerant resurrection plant
      Myrothamnus flabellifolia.
AB  - BACKGROUND: Myrothamnus flabellifolia is unique as the only woody resurrection
      plant. It is an important plant in southern Africa because of its widespread
      occurrence and usage in African medicine and traditional culture. Many reports
      have investigated facets of its biology and the mechanisms associated with its
      desiccation tolerance. SCOPE: The general biology of the woody resurrection plant
      Myrothamnus flabellifolia is reviewed. The review focuses on the geography and
      ecology, systematic placement, evolution, morphology and reproductive ecology of
      M. flabellifolia as well as the wood anatomy and re-filling mechanism. In
      addition, the desiccation tolerance, ethnobotanical importance and medicinal
      properties of the plant are reviewed. Also, future research avenues are
      suggested, in particular the necessity to research the biogeography and
      systematics of the species and the role of the polyphenols present, as well as
      the molecular basis of the plant's desiccation tolerance.

PMID- 17218344
TI  - Total and component carbon fluxes of a Scots pine ecosystem from chamber
      measurements and eddy covariance.
AB  - BACKGROUND AND AIMS: Distinguishing between, and quantifying, the different
      components of ecosystem C fluxes is critical in predicting the responses of
      ecosystem C cycling to climate change. The aims of this study were to quantify
      the photosynthetic and respiratory fluxes of a 50-year-old Scots pine (Pinus
      sylvestris) ecosystem, and to distinguish respiration of branches with needles
      from that of stems, and that of soil. METHODS: The CO2 flux of the ecosystem was
      continuously measured using the eddy covariance (EC) method, and its components
      (respiration and photosynthesis of a branch with needles, stem and soil surface)
      were measured with an automated chamber system, from 2001 to 2004. KEY RESULTS:
      All values below are chamber based. The average temperature coefficient (Q10) of
      respiration was 2.7, 2.2 and 4.0, respectively, for branch (Rbran), stem (Rstem)
      and the soil surface (Rsoil). Respiration at a reference temperature of 15
      degrees C (R15) was 1.27, 0.49 and 4.02 micromol CO2 m(-2) ground s(-1) for the
      three components, respectively. Over 4 years, the annual Rbran, Rstem and Rsoil
      ranged from 196 to 256, 56 to 83 and 439 to 598 g C m(-2) ground year(-1),
      respectively, with a 4-year average of 227, 72 and 507 g C m(-2) ground year(-1).
      Annual ecosystem respiration (Reco) was 731, 783, 909 and 751 g C m(-2) ground
      year(-1) in years 2001-2004, respectively, gross primary production (GPP) was
      922, 1030, 1138 and 1001 g C m(-2) ground year(-1), and net ecosystem production
      (NEP) was 191, 247, 229 and 251 g C m(-2) ground year(-1). The average
      contribution of Rbran, Rstem and Rsoil to Reco was 29, 9 and 62 %, respectively.
      Overstorey photosynthesis accounted for 96 % of GPP. The average Reco/GPP ratio
      was 0.78. Net primary production (NPP) in the 4 years was 469, 581, 600 and 551 g
      C m(-2) year(-1), respectively, with the NPP/GPP ratio 0.54 averaged over the
      years. CONCLUSIONS: Respiration from the soil is the dominant component of
      ecosystem respiration. Differences between years in Reco were due to differences
      in temperature during the growing season. Rsoil was more sensitive to temperature
      than Rbran and Rstem, and differences in Rsoil were responsible for the
      differences in Reco between years.

PMID- 17218345
TI  - Current-year and subsequent-year effects of crop-load manipulation and epicormic
      shoot removal on distribution of long, short and epicormic shoot growth in Prunus
      persica.
AB  - BACKGROUND AND AIMS: The distribution of canopy growth among different shoot
      types such as epicormic, long and short shoots is not well understood in the
      peach tree. In this experiment, the effects of crop load and early epicormic
      sprout removal on current and subsequent-year distribution of vegetative growth
      among epicormic, long and short shoots was investigated in Prunus persica.
      METHODS: Field trials were conducted in Winters, California, in 2003-2004. Crop
      load was manipulated with fruit thinning in 2003 to produce trees that were de
      fruited, commercially thinned or full crop, and half of the trees in each
      cropping treatment had all current year epicormic sprouts removed at the time of
      fruit thinning. Yield was recorded and trunk and root carbohydrates were sampled
      to confirm the effect of 2003 crop load differences on tissue carbohydrate
      concentration. All current-season vegetative-shoot extension growth was harvested
      from half of the trees in each treatment in the autumn of 2003 and from the other
      half in the autumn of 2004. Epicormic, long and short shoots were separately
      evaluated for dry weight, node number and leaf-stem parameters. KEY RESULTS: In
      2003, long-shoot dry weight and node number were significantly affected by crop
      load; however, short-shoot dry weight and node number were not significantly
      affected. The 2003 crop-load treatments did not affect 2004 vegetative growth of
      any shoot type. Some re-growth of epicormic shoots followed early epicormic
      sprout removal: by the end of the 2003 season, trees in the early shoot-removal
      treatment had approximately one-third of the epicormic-shoot dry weight as
      unpruned trees. CONCLUSIONS: Fruit thinning promoted distribution of growth
      similar to that of de-fruited trees. While thinning was effective in increasing
      fruit size, it exacerbated the problem of epicormic sprouting. Early epicormic
      sprout removal did not stimulate the excessive epicormic re-growth in the same or
      subsequent year relative to previously studied summer pruning methods.

PMID- 17218347
TI  - Health promotion at NHS breast cancer screening clinics in the UK.
AB  - Suboptimal diets, sedentary lifestyles, overweight and obesity expose two-thirds
      of women in England aged over 50 to a heightened risk of lifestyle-related
      morbidities. The UK's NHS Breast Cancer Screening Programme now reaches 75% of
      all women aged 53-64 but provides only mammography screening. This cross
      sectional survey of 413 women attending two NHS breast screening clinics in North
      Yorkshire found that the majority of women were interested in having diet and
      exercise advice at screening clinics and anticipated a neutral or positive effect
      on their future screening appointments. Interest was highest among older, less
      educated and overweight women suggesting that this may be a particularly
      effective medium for reaching higher risk subgroups. Women showed most interest
      in problem-solving advice, which provided short-term, life-enhancing benefits
      such as looking and feeling better, having more energy, losing weight and
      reducing menopausal symptoms, as well as potentially reducing their disease risk.
      Most appeared to find doing sufficient exercise more problematic than eating
      healthily and this might be exacerbated by low awareness of exercise guidelines.
      Given a choice, preferences were to access advice in leaflets or one to one from
      an expert; however, many younger, professional women were also interested in
      computer access. Findings indicate the need first for flexible, multi-level
      access, combining some broad-based information dissemination with pathways to
      more personalized support and secondly for the relevant 'consumer benefits'
      associated with better diet and exercise to be promoted as well as longer-term
      disease prevention. Overall, this study indicates that the UK's NHS Breast Cancer
      Screening Programme may be uniquely placed to provide health-enhancing advice as
      well as mammography screening to the majority of women in England, throughout the
      course of their mid-life.

PMID- 17218346
TI  - Plant architecture: a dynamic, multilevel and comprehensive approach to plant
      form, structure and ontogeny.
AB  - BACKGROUND AND AIMS: The architecture of a plant depends on the nature and
      relative arrangement of each of its parts; it is, at any given time, the
      expression of an equilibrium between endogenous growth processes and exogenous
      constraints exerted by the environment. The aim of architectural analysis is, by
      means of observation and sometimes experimentation, to identify and understand
      these endogenous processes and to separate them from the plasticity of their
      expression resulting from external influences. SCOPE: Using the identification of
      several morphological criteria and considering the plant as a whole, from
      germination to death, architectural analysis is essentially a detailed,
      multilevel, comprehensive and dynamic approach to plant development. Despite
      their recent origin, architectural concepts and analysis methods provide a
      powerful tool for studying plant form and ontogeny. Completed by precise
      morphological observations and appropriated quantitative methods of analysis,
      recent researches in this field have greatly increased our understanding of plant
      structure and development and have led to the establishment of a real conceptual
      and methodological framework for plant form and structure analysis and
      representation. This paper is a summarized update of current knowledge on plant
      architecture and morphology; its implication and possible role in various aspects
      of modern plant biology is also discussed.

PMID- 17218348
TI  - Molecular basis of the T- and L-type Ca2+ currents in canine Purkinje fibres.
AB  - This study examines the molecular basis for the T-type and L-type Ca(2+) currents
      in canine Purkinje cells. The I(CaT) in Purkinje cells was completely suppressed
      by 200 nM kurtoxin, a specific blocker of both Ca(v)3.1 and Ca(v)3.2 channels.
      Since only Ca(v)3.2 mRNA is expressed at high levels in Purkinje fibres, being
      approximately 100-fold more abundant than either Ca(v)3.1 or Ca(v)3.3 mRNAs, it
      is concluded that the Ca(v)3.2 gene encodes the bulk of the T-type Ca(2+)
      channels in canine Purkinje cells. This conclusion is consistent with the
      sensitivity of the current to blockade by Ni(2+) ions (K(D) = 32 microM). For L
      type channels, Ca(v)1.2 mRNA was most abundant in Purkinje fibres but a
      significant level of Ca(v)1.3 mRNA expression was also found. A comparison of the
      sensitivity to blockade by isradipine of the L-type currents in Purkinje cells
      and ventricular epicardial myocytes, which only express Ca(v)1.2, suggests that
      the Ca(v)1.3 channels make, at most, a minor contribution to the L-type current
      in canine Purkinje cells.

PMID- 17218349
TI  - Regional recruitment of rat diaphragmatic lymphatics in response to increased
      pleural or peritoneal fluid load.
AB  - The specific role of the diaphragmatic tendinous and muscular tissues in
      sustaining lymph formation and propulsion in the diaphragm was studied in 24
      anaesthetized spontaneously breathing supine rats. Three experimental protocols
      were used: (a) control; (b) peritoneal ascitis, induced through an
      intraperitoneal injection of 100 ml kg(-1) of iso-oncotic saline; and (c) pleural
      effusion, induced through an intrapleural injection of 6.6 ml kg(-1) saline
      solution. A group of animals (n = 12) was instrumented to measure the hydraulic
      transdiaphragmatic pressure gradient between the pleural and peritoneal cavities
      in the three protocols. In the other group (n = 12), the injected iso-oncotic
      saline was enriched with 2% fluorescent dextrans (molecular mass = 70 kDa); at 30
      min from the injections these animals were suppressed and their diaphragm excised
      and processed for confocal microscopy analysis. In control conditions, in spite
      of a favourable peritoneal-to-pleural pressure gradient, the majority of the
      tracer absorbed into the diaphragmatic lymphatic system converges towards the
      deeper collecting lymphatic ducts. This suggests that diaphragmatic lymph
      formation mostly depends upon pressure gradients developing between the serosal
      cavities and the lymphatic vessel lumen. In addition, the tracer distributes to
      lymph vessels located in the muscular diaphragmatic tissue, suggesting that
      active muscle contraction, rather than passive tendon stretch, more efficiently
      enhances local diaphragmatic lymph flow. Vice versa, a prevailing recruitment of
      the lymphatics of the tendinous diaphragmatic regions was observed in peritoneal
      ascitis and pleural effusion, suggesting a functional adaptation of the
      diaphragmatic network to increased draining requirements.

PMID- 17218350
TI  - The kinetics of inhibition of rat recombinant heteromeric alpha1beta glycine
      receptors by the low-affinity antagonist SR-95531.
AB  - The GABA(A) antagonist SR-95531 (gabazine) is known to block glycine receptors,
      albeit with low affinity. We have studied the effect of SR-95531 on rat
      recombinant alpha1beta glycine receptors expressed in human embryonic kidney
      (HEK293) cells by recording macroscopic currents elicited by rapid glycine
      application to outside-out patches. SR-95531 has a fast unbinding rate (k(offSR),
      about 3000 s(-1)) and this means that the time course of its unbinding is
      comparable to the expected time course of the transmitter in the cleft. We also
      found that equilibrium applications of SR-95531 reduced the response to brief
      glycine applications by an amount inversely proportional to the duration of
      glycine application. The fast unbinding rate of SR-95531 from the glycine
      receptor will make it useful for establishing the time course of glycine
      concentration at glycinergic synapses.

PMID- 17218352
TI  - Differential control of the scapulothoracic muscles in humans.
AB  - The control of the scapulothoracic muscles trapezius (Tr) and serratus anterior
      (SA) has been examined in normal human subjects. Electromyographic recordings
      were made from the SA and Tr muscles (upper trapezius UTr, lower trapezius LTr)
      using surface electrodes placed bilaterally. Magnetic stimulation of the motor
      cortex and electrical stimulation of peripheral nerves were used to examine their
      descending and reflex control. The average optimal site of cortical stimulation
      was found to be the same for SA, UTr and LTr (an approximate centre of gravity of
      -0.6 cm, 3.7 cm where the centre of gravity is expressed as the mean anterio
      posterior position, the mean medio-lateral position). Some asymmetry in the
      cortical representation of UTr was found in each individual tested. Magnetic
      stimulation evoked bilateral MEPs in Tr (latency contralateral (c) UTr 8.5 +/-
      1.6 ms, ipsilateral (i) UTr 19.0 +/- 2.7 ms) but only contralateral responses
      were evoked in SA (11.2 +/- 2.6 ms). Electrical stimulation of the long thoracic
      nerve at two sites was used to examine homonymous and heteronymous reflexes of
      SA, while electrical stimulation of cervical nerve of C3/4 was used to examine
      the heteronymous reflexes of Tr. Ipsilateral SA H reflexes were evoked at a
      latency of 9.9 +/- 0.8 ms (proximal site) and 10.8 +/- 1.2 ms (distal site). No
      group I reflexes were evoked from SA to its contralateral homologue. No group I
      reflexes were evoked between Tr and SA. Finally, cross-correlation of activity
      from the Tr muscle pairs and the SA muscle pair revealed that the motoneurones of
      the Tr muscles share some common presynaptic input whereas there was no
      detectable common presynaptic input to the SA muscle pair. This study extends and
      consolidates knowledge regarding the neural control of trapezius and for the
      first time explores the neural control of SA. The study demonstrates a
      contrasting bilateral control of Tr and SA. These patterns of connections are
      discussed in relation to the contrasting bilateral functional roles of these
      muscles.

PMID- 17218351
TI  - Stimulation-induced changes in NADH fluorescence and mitochondrial membrane
      potential in lizard motor nerve terminals.
AB  - To investigate mitochondrial responses to repetitive stimulation, we measured
      changes in NADH fluorescence and mitochondrial membrane potential (Psi(m))
      produced by trains of action potentials (50 Hz for 10-50 s) delivered to motor
      nerve terminals innervating external intercostal muscles. Stimulation produced a
      rapid decrease in NADH fluorescence and partial depolarization of Psi(m). These
      changes were blocked when Ca2+ was removed from the bath or when N-type Ca2+
      channels were inhibited with omega-conotoxin GVIA, but were not blocked when bath
      Ca2+ was replaced by Sr2+, or when vesicular release was inhibited with botulinum
      toxin A. When stimulation stopped, NADH fluorescence and Psi(m) returned to
      baseline values much faster than mitochondrial [Ca2+]. In contrast to findings in
      other tissues, there was usually little or no poststimulation overshoot of NADH
      fluorescence. These findings suggest that the major change in motor terminal
      mitochondrial function brought about by repetitive stimulation is a rapid
      acceleration of electron transport chain (ETC) activity due to the Psi(m)
      depolarization produced by mitochondrial Ca2+ (or Sr2+) influx. After partial
      inhibition of complex I of the ETC with amytal, stimulation produced greater
      Psi(m) depolarization and a greater elevation of cytosolic [Ca2+]. These results
      suggest that the ability to accelerate ETC activity is important for normal
      mitochondrial sequestration of stimulation-induced Ca2+ loads.

PMID- 17218353
TI  - The physiology of a local renin-angiotensin system in the pancreas.
AB  - The systemic renin-angiotensin system (RAS) plays an important role in regulating
      blood pressure, electrolyte and fluid homeostasis. However, local RASs also exist
      in diverse tissues and organs, where they play a multitude of autocrine,
      paracrine and intracrine physiological roles. The existence of a local RAS is now
      recognized in pancreatic acinar, islet, duct, endothelial and stellate cells, the
      expression of which is modulated in response to physiological and
      pathophysiological stimuli such as hypoxia, pancreatitis, islet transplantation,
      hyperglycaemia, and diabetes mellitus. This pancreatic RAS has been proposed to
      have important endocrine and exocrine roles in the pancreas, regulating local
      blood flow, duct cell sodium bicarbonate secretion, acinar cell digestive enzyme
      secretion, islet beta-cell (pro)insulin biosynthesis, and thus, glucose
      stimulated insulin release, delta-cell somatostatin secretion, and pancreatic
      cell proliferation and differentiation. It may further mediate oxidative stress
      induced cell inflammation, apoptosis and fibrosis. Further exploration of this
      system would probably offer new insights into the pathogenesis of pancreatitis,
      diabetes, cystic fibrosis and pancreatic cancer formation. New therapeutic
      targets and strategies might thus be suggested.

PMID- 17218354
TI  - Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats:
      effects on cardiovascular parameters.
AB  - Epidemiological studies have shown a strong correlation between stressful events
      (nutritional, hormonal or environmental) in early life and development of adult
      diseases such as obesity, diabetes and cardiovascular failure. It is known that
      gestation and lactation are crucial periods for healthy growth in mammals and
      that the sympathoadrenal system is markedly influenced by environmental
      conditions during these periods. We previously demonstrated that neonatal
      hyperleptinaemia in rats programmes higher body weight, higher food intake and
      hypothalamic leptin resistance in adulthood. Using this model of programming, we
      investigated adrenal medullary function and effects on cardiovascular parameters
      in male rats in adulthood. Leptin treatment during the first 10 days of lactation
      (8 microg 100 g(-1) day(-1), s.c.) resulted in lower body weight (6.5%, P <
      0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in
      adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150
      days), the rats presented higher body weight (5%, P < 0.05), adrenal
      catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P
      < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%,
      respectively, P < 0.05). Systolic blood pressure and heart rate were also higher
      in adult rats (7% and 6%, respectively, P < 0.05). Our results show that
      hyperleptinaemia in early life increases adrenal medullary function in adulthood
      and that this may alter cardiovascular parameters. Thus, we suggest that
      imprinting factors which increase leptin and catecholamine levels during the
      neonatal period could be involved in development of adult chronic diseases.

PMID- 17218355
TI  - Altered synaptic input and GABAB receptor function in spinal superficial dorsal
      horn neurons in rats with diabetic neuropathy.
AB  - Hyperactivity of spinal dorsal horn neurons plays an important role in the
      development of diabetic neuropathic pain. However, little is known as to whether
      synaptic input to spinal dorsal horn neurons is altered in diabetic neuropathy.
      Also, the function of GABAB receptors in the control of synaptic input to dorsal
      horn neurons in diabetes remains poorly understood. To determine the changes in
      synaptic input to dorsal horn neurons and the GABAB)receptor function in
      streptozotocin-induced diabetes, we performed whole-cell recording (GDP-beta-S
      included in the internal solution) on lamina II neurons in rat spinal cord
      slices. The frequency of glutamatergic mEPSCs and the amplitude of monosynaptic
      EPSCs evoked from the dorsal root were significantly higher in diabetic than in
      control rats. On the other hand, the basal frequency and amplitude of GABAergic
      spontaneous IPSCs and mIPSCs and those of glycinergic spontaneous IPSCs and
      mIPSCs did not differ significantly between control and diabetic rats. The GABAB
      agonist baclofen produced a significantly greater reduction in dorsal root-evoked
      EPSCs and the frequency of mEPSCs in control than in diabetic rats. However, the
      inhibitory effect of baclofen on GABAergic and glycinergic spontaneous IPSCs and
      mIPSCs was not significantly different in the two groups. These findings suggest
      that increased glutamatergic input from primary afferents to dorsal horn neurons
      may contribute to synaptic plasticity and central sensitization in diabetic
      neuropathic pain. Furthermore, the function of presynaptic GABAB receptors at
      primary afferent terminals, but not that on GABAergic and glycinergic
      interneurons, in the spinal cord is reduced in diabetic neuropathy.

PMID- 17218356
TI  - Ionic currents underlying the response of rat dorsal vagal neurones to
      hypoglycaemia and chemical anoxia.
AB  - A proportion of dorsal vagal neurones (DVN) are glucosensors. These cells respond
      to brief hypoglycaemia either with a K(ATP) channel-mediated hyperpolarization or
      with depolarization owing to an as yet unknown mechanism. K(ATP) currents are
      observed not only during hypoglycaemia, but also in response to mitochondrial
      inhibition. Here we show that similarly to the observations for K(ATP) currents,
      both hypoglycaemia and inhibition of mitochondrial function elicited a small
      inward current that persisted in TTX in DVN of rat brainstem slices. Removal of
      glucose from the bath solution induced this inward current within 50 +/- 4 s in
      one subpopulation of DVN and in 279 +/- 36 s in another subpopulation. No such
      subpopulations were observed for the response to mitochondrial inhibition.
      Biophysical analysis revealed that mitochondrial inhibition or hypoglycaemia
      inhibited an openly rectifying K+ conductance in 25% of DVN. In the remaining
      cells, either an increase in conductance, with a reversal potential between -58
      and +10 mV, or a parallel inward shift of the holding current was observed. This
      current most probably resulted from inhibition of the Na+-K+-ATPase and/or the
      opening of an ion channel. Recordings with electrodes containing 145 mm instead
      of 5 mm Cl- failed to shift the reversal potential of the inward current,
      indicating that a Cl- channel was not involved. In summary, glucosensing and non
      glucosensing DVN appear to use common electrical pathways to respond to
      mitochondrial inhibition and to hypoglycaemia. We suggest that differences in
      glucose metabolism rather than differences in the complement of ion channels
      distinguish these two cell types.

PMID- 17218357
TI  - Muscle fatigue changes cutaneous suppression of propriospinal drive to human
      upper limb muscles.
AB  - Some voluntary drive reaches human upper limb muscles via cervical propriospinal
      premotoneurones. Stimulation of the superficial radial nerve can inhibit these
      premotoneurones selectively and the resultant suppression of voluntary drive to
      motoneurones changes on-going electromyographic (EMG) activity. We investigated
      whether muscle fatigue changes this cutaneous-induced suppression of
      propriospinal drive to motoneurones of upper limb muscles. EMG was recorded from
      the extensors and flexors of the wrist and elbow. In the first study (n = 10
      subjects), single stimuli (2 x perception threshold; 2PT) to the superficial
      radial nerve were delivered during contraction of the wrist extensors, before and
      after sustained fatiguing contractions of wrist extensors. In the second study (n
      = 10), similar stimuli were applied during elbow extension, before and during
      fatigue of elbow extensors. In the final study (n = 10), trains of three stimuli
      (2PT) were delivered during contractions of wrist extensors, before and while
      they were fatigued. With fatigue of either the wrist or elbow extensors, EMG
      suppression to single cutaneous stimuli increased significantly (by approximately
      75%) for the fatigued muscle (P < 0.05). Conversely, in the other muscles, which
      were coactivated but not principally involved in the task, inhibition decreased
      or facilitation increased. Trains of stimuli produced greater suppression of on
      going wrist extensor EMG than single stimuli and this difference persisted with
      fatigue. A control study of the H reflex in extensor carpi radialis showed that
      the mechanism responsible for the altered EMG suppression in fatigue was not at a
      motoneurone level. The findings suggest that the proportion of descending drive
      mediated via the disynaptic propriospinal pathway or the excitability of
      inhibitory interneurones projecting to propriospinal neurones increases
      substantially to fatigued muscles, but decreases to other active muscles. This
      pattern of changes may maintain coordination during multimuscle movements when
      one group of muscles is fatigued.

PMID- 17218358
TI  - Role of the store-operated calcium entry proteins Stim1 and Orai1 in muscarinic
      cholinergic receptor-stimulated calcium oscillations in human embryonic kidney
      cells.
AB  - We have investigated the nature of the Ca2+ entry supporting [Ca2+]i oscillations
      in human embryonic kidney (HEK293) cells by examining the roles of recently
      described store-operated Ca2+ entry proteins, Stim1 and Orai1. Knockdown of Stim1
      by RNA interference (RNAi) reduced the frequency of [Ca2+]i oscillations in
      response to a low concentration of methacholine to the level seen in the absence
      of external Ca2+. However, knockdown of Stim1 did not block oscillations in
      canomical transient receptor potential 3 channel (TRPC3)-expressing cells and did
      not affect Ca2+ entry in response to arachidonic acid. The effects of knockdown
      of Stim1 could be reversed by inhibiting Ca2+ extrusion with a high concentration
      of Gd3+, or by rescuing the knockdown by overexpression of Stim1. Similarly,
      knockdown of Orai1 abrogated [Ca2+]i oscillations, and this was reversed by use
      of high concentrations of Gd3+; however, knockdown of Orai1 did not affect
      arachidonic acid-activated entry. RNAi targeting 34 members of the transient
      receptor potential (TRP) channel superfamily did not reveal a role for any of
      these channel proteins in store-operated Ca2+ entry in HEK293 cells. These
      findings indicate that the Ca2+ entry supporting [Ca2+]i oscillations in HEK293
      cells depends upon the Ca2+ sensor, Stim1, and calcium release-activated Ca2+
      channel protein, Orai1, and provide further support for our conclusion that it is
      the store-operated mechanism that plays the major role in this pathway.

PMID- 17218359
TI  - Multivesicular release and saturation of glutamatergic signalling at retinal
      ribbon synapses.
AB  - Pronounced multivesicular release (MVR) occurs at the ribbon synapses of sensory
      neurones that signal via graded potential changes. As MVR increases the
      likelihood of postsynaptic receptor saturation, it is of interest to consider how
      sensory synapses overcome this problem and use MVR to encode signals of widely
      varying intensities. Here, I discuss three postsynaptic mechanisms that permit
      three different retinal synapses to utilize MVR.

PMID- 17218360
TI  - CRAC channel activity in C. elegans is mediated by Orai1 and STIM1 homologues and
      is essential for ovulation and fertility.
AB  - The Ca(2+) release-activated Ca(2+) (CRAC) channel is a plasma membrane Ca(2+)
      entry pathway activated by endoplasmic reticulum (ER) Ca(2+) store depletion.
      STIM1 proteins function as ER Ca(2+) sensors and regulate CRAC channel
      activation. Recent studies have demonstrated that CRAC channels are encoded by
      the human Orai1 gene and a homologous Drosophila gene. C. elegans intestinal
      cells express a store-operated Ca(2+) channel (SOCC) regulated by STIM-1. We
      cloned a full-length C. elegans cDNA that encodes a 293 amino acid protein, ORAI
      1, homologous to human and Drosophila Orai1 proteins. ORAI-1 GFP reporters are co
      expressed with STIM-1 in the gonad and intestine. Inositol 1,4,5-trisphosphate
      (IP(3))-dependent Ca(2+) signalling regulates C. elegans gonad function,
      fertility and rhythmic posterior body wall muscle contraction (pBoc) required for
      defecation. RNA interference (RNAi) silencing of orai-1 expression phenocopies
      stim-1 knockdown and causes sterility and prevents intestinal cell SOCC
      activation, but has no effect on pBoc or intestinal Ca(2+) signalling. Orai-1
      RNAi suppresses pBoc defects induced by intestinal expression of a STIM-1 Ca(2+)
      binding mutant, indicating that the proteins function in a common pathway. Co
      expression of stim-1 and orai-1 cDNAs in HEK293 cells induces large inwardly
      rectifying cation currents activated by ER Ca(2+) depletion. The properties of
      this current recapitulate those of the native SOCC current. We conclude that C.
      elegans expresses bona fide CRAC channels that require the function of Orai1- and
      STIM1-related proteins. CRAC channels thus arose very early in animal evolution.
      In C. elegans, CRAC channels do not play obligate roles in all IP(3)-dependent
      signalling processes and ER Ca(2+) homeostasis. Instead, we suggest that CRAC
      channels carry out highly specialized and cell-specific signalling roles and that
      they may function as a failsafe mechanism to prevent Ca(2+) store depletion under
      pathophysiological and stress conditions.

PMID- 17218361
TI  - Fetal body weight and the development of the control of the cardiovascular system
      in fetal sheep.
AB  - Reduced birth weight predisposes to cardiovascular diseases in later life. We
      examined in fetal sheep at 0.76 (n = 18) and 0.87 (n = 17) gestation whether
      spontaneously occurring variations in fetal weight affect maturation of autonomic
      control of cardiovascular function. Fetal weights at both gestational ages were
      grouped statistically in low (LW) and normal weights (NW) (P < 0.01). LW fetuses
      were within the normal weight span showing minor growth dysproportionality at
      0.76 gestation favouring heart and brain, with a primary growth of carcass
      between 0.76 and 0.87 gestation (P < 0.05). While twins largely contributed to LW
      fetuses, weight differences between singletons and twins were absent at 0.76 and
      modest at 0.87 gestation, underscoring the fact that twins belong to normality in
      fetal sheep not constituting a major malnutritive condition. Mean fetal blood
      pressure (FBP) of all fetuses was negatively correlated to fetal weight at 0.76
      but not 0.87 gestation (P < 0.05). At this age, FBP and baroreceptor reflex
      sensitivity were increased in LW fetuses (P < 0.05), suggesting increased
      sympathetic activity and immaturity of circulatory control. Development of vagal
      modulation of fetal heart rate depended on fetal weight (P < 0.01). These
      functional associations were largely independent of twin pregnancies. We
      conclude, low fetal weight within the normal weight span is accompanied by a
      different trajectory of development of sympathetic blood pressure and vagal heart
      rate control. This may contribute to the development of elevated blood pressure
      in later life. Examination of the underlying mechanisms and consequences may
      contribute to the understanding of programming of cardiovascular diseases.

PMID- 17218362
TI  - Effect of acetazolamide on pulmonary and muscle gas exchange during normoxic and
      hypoxic exercise.
AB  - Acetazolamide (ACZ) is used to prevent acute mountain sickness at altitude.
      Because it could affect O2 transport in several different and potentially
      conflicting ways, we examined its effects on pulmonary and muscle gas exchange
      and acid-base status during cycle exercise at approximately 30, 50 and 90% VO2max
      in normoxia (F(IO2) = 0.2093) and acute hypoxia (F(IO2) = 0.125). In a double
      blind, order-balanced, crossover design, six healthy, trained men (normoxic
      VO2max= 59 ml kg(-1) min(-1)) exercised at both F(IO2) values after ACZ (3 doses
      of 250 mg, 8 h apart) and placebo. One week later this protocol was repeated
      using the other drug (placebo or ACZ). We measured cardiac output (QT), leg blood
      flow (LBF), and muscle and pulmonary gas exchange, the latter using the multiple
      inert gas elimination technique. ACZ did not significantly affect VO2, QT, LBF or
      muscle gas exchange. As expected, ACZ led to lower arterial and venous blood
      [HCO3-], pH and lactate levels (P < 0.05), and increased ventilation (P < 0.05).
      In both normoxia and hypoxia, ACZ resulted in higher arterial P(O2) and
      saturation and a lower alveolar-arterial P(O2) difference (AaD(O2)) due to both
      less VA/Q mismatch and less diffusion limitation (P < 0.05). In summary, ACZ
      improved arterial oxygenation during exercise, due to both greater ventilation
      and more efficient pulmonary gas exchange. However, muscle gas exchange was
      unaffected.

PMID- 17218363
TI  - Alterations in mRNA expression and protein products following spinal cord injury
      in humans.
AB  - We examined the effects of spinal cord injury (SCI) on alterations in gene
      expression and respective protein products in human skeletal muscle 2 days and 5
      days post-SCI. Biopsies were taken from skeletal muscle of 9 men and 1 woman (n =
      10) (43.9 +/- 6.7 years) 2 days and 5 days post-SCI and from 5 healthy young men
      who served as controls (20.4 +/- 0.5 years). Global changes in gene expression
      were analysed using Affymetrix GeneChips on a subsample of subjects (n = 3).
      Candidate genes were then pursued via qRT-PCR. Western blotting (WB) was used to
      quantify protein products of candidate genes. Immunohistochemistry (IHC) was used
      to localize proteins. Groups of transcripts showing the greatest percentage of
      altered expression, the most robust fold-changes, and indicative of involvement
      of an entire pathway using the GeneChip included genes involved in the ubiquitin
      proteasome pathway (UPP), metallothionein function, and protease inhibition. qRT
      PCR analysis confirmed increases in gene expression for UPP components (UBE3C,
      Atrogin-1, MURF1, and PSMD11), the metallothioneins (MT1A, MT1F, MT1H), and the
      protease inhibitor, SLPI (P < 0.05) at 2 days and 5 days post-SCI. Protein levels
      of the proteasome subunit (PSMD11) and the metallothioneins were increased 5 days
      post-SCI. Protein levels of UBE3C, Atrogin-1, MURF1 and SLPI were unchanged (P >
      0.05). IHC showed increased staining for PSMD11 and the metallothioneins 5 days
      post-SCI, along the peripheral region of the cells. IHC also showed altered
      staining for Atrogin-1 at 5 days post-SCI along the membrane region. Thus, there
      was a profound increase in gene expression of UPP components, the
      metallothioneins, and the protease inhibitor, SLPI, within 5 days of SCI.
      Increased protein levels for PSMD11 and the metallothioneins 5 days post-SCI,
      specifically along the cell periphery, indicate that proteins in this region may
      be early targets for degradation post-SCI.

PMID- 17218364
TI  - The relationship between exposure to alcohol advertising in stores, owning
      alcohol promotional items, and adolescent alcohol use.
AB  - AIM: This paper describes adolescents' exposure to alcohol advertising in stores
      and to alcohol-branded promotional items and their association with self-reported
      drinking. METHODS: A cross-sectional survey was administered in non-tracked
      required courses to sixth, seventh, and eighth graders (n = 2125) in three
      California middle schools. Logistic regressions compared the odds of ever (vs.
      never) drinking and current (vs. ever) drinking after controlling for
      psychosocial and other risk factors for adolescent alcohol use. RESULTS: Two
      thirds of middle school students reported at least weekly visits to liquor,
      convenience, or small grocery stores where alcohol advertising is widespread.
      Such exposure was associated with higher odds of ever drinking, but was not
      associated with current drinking. One-fifth of students reported owning at least
      one alcohol promotional item. These students were three times more likely to have
      ever tried drinking and 1.5 times more likely to report current drinking than
      students without such items. CONCLUSIONS: This study provides clear evidence of
      an association of adolescent drinking with weekly exposure to alcohol advertising
      in stores and with ownership of alcohol promotional items. Given their potential
      influence on adolescent drinking behaviour, retail ads, and promotional items for
      alcohol deserve further study.

PMID- 17218365
TI  - Modeling lung cancer incidence in rats following exposure to radon progeny.
AB  - Lung cancer incidence in Sprague-Dawley rats was simulated by a biologically
      based carcinogenesis model, which is formulated mathematically in terms of a
      stochastic state-vector model. Doses to the sensitive target cells in the
      bronchial epithelium of the rat lung were calculated by a stochastic dosimetry
      model, considering the distinct monopodial branching structure and the crossfire
      of alpha particles from alveolar tissue to bronchial epithelium. Bronchial and
      alveolar cellular doses could reasonably be approximated by lognormal
      distributions, with geometric standard deviations (GSD) between 7 and 10,
      depending on exposure conditions. Based on a dose-exposure conversion factor of
      8.5 mGy WLM(-1) and a GSD of 8, lung cancer incidences were calculated for each
      cumulative exposure category in the rat inhalation study, consisting of different
      exposure rates and exposure times. The fair agreement between theoretical
      predictions and experimental data over the whole exposure range emphasises the
      necessity to incorporate the full cellular dose distributions rather than their
      mean values.

PMID- 17218366
TI  - Bayesian reconstruction of nanodosimetric cluster distributions at 100% detection
      efficiency.
AB  - Ionisation spectra in nanometric volumes at a given distance from a charged
      particle track are obtained by using electron (or ion) gas detectors, having non
      uniformly distributed detection efficiency. Therefore, such spectra should be
      properly processed in order to reconstruct the frequency distribution of clusters
      really produced in the detector gas. A Bayesian unfolding has been applied to
      ionisation distributions due to 5.4 MeV alpha particles in a 20-nm site obtained
      by Monte Carlo simulations, taking into account different detection efficiency
      conditions. It will be shown that Bayesian analysis provides a valid tool for
      reconstructing the true ionisation distributions, well beyond the maximum
      measured cluster size.

PMID- 17218367
TI  - Doses and LET spectra in the beam of 12C with energy 500 MeV amu-1.
AB  - This paper describes the results of experimental studies performed at the Joint
      Institute for Nuclear Research (JINR) in a (12)C ion beam with the primary
      nominal energy 500 MeV amu(-1). Data measured by means of a diamond detector and
      a spectrometer of linear energy transfer (LET) based on chemically etched track
      detectors are presented, analysed and discussed. LET spectra are also calculated
      by program SRIM.

PMID- 17218368
TI  - Development of a single ion hit facility at the Pierre Sue Laboratory: a
      collimated microbeam to study radiological effects on targeted living cells.
AB  - A single ion hit facility is being developed at the Pierre Sue Laboratory (LPS)
      since 2004. This set-up will be dedicated to the study of ionising radiation
      effects on living cells, which will complete current research conducted on
      uranium chemical toxicity on renal and osteoblastic cells. The study of the
      response to an exposure to alpha particles will allow us to distinguish
      radiological and chemical toxicities of uranium, with a special emphasis on the
      bystander effect at low doses. Designed and installed on the LPS Nuclear
      microprobe, up to now dedicated to ion beam microanalysis, this set-up will
      enable us to deliver an exact number of light ions accelerated by a 3.75 MV
      electrostatic accelerator. An 'in air' vertical beam permits the irradiation of
      cells in conditions compatible with cell culture techniques. Furthermore,
      cellular monolayer will be kept in controlled conditions of temperature and
      atmosphere in order to diminish stress. The beam is collimated with a fused
      silica capillary tubing to target pre-selected cells. Motorisation of the
      collimator with piezo-electric actuators should enable fast irradiation without
      moving the sample, thus avoiding mechanical stress. An automated epifluorescence
      microscope, mounted on an antivibration table, allows pre- and post-irradiation
      cell observation. An ultra thin silicon surface barrier detector has been
      developed and tested to be able to shoot a cell with a single alpha particle.

PMID- 17218369
TI  - Serum mullerian-inhibiting substance in Down's syndrome pregnancies.
AB  - BACKGROUND: To examine whether maternal serum levels of mullerian-inhibiting
      substance (MIS) differ in Down's syndrome and unaffected pregnancies. METHODS:
      Case-control study was conducted using stored serum from an antenatal screening
      programme. Sera from 25 Down's syndrome pregnancies were retrieved from -20
      degrees C storage together with 125 unaffected controls individually matched for
      maternal age, weeks of gestation and duration of storage. Results were expressed
      in multiples of the gestation-specific median value (MoM) in controls. RESULTS:
      The median value in Down's syndrome pregnancies was 0.83 MoM (P = 0.77, two-tail
      Wilcoxon rank sum test). Among unaffected pregnancies, there was a statistically
      significant correlation between MIS and pregnancy-associated plasma protein-A (P
      < 0.05). MIS levels were elevated in pregnancies where assisted reproduction
      techniques had been used. CONCLUSION: There is no evidence for a substantial
      reduction in maternal serum MIS levels in Down's syndrome pregnancies. This study
      provides useful information regarding serum MIS levels in pregnancy.

PMID- 17218370
TI  - Follicle growth is inhibited by benzo-[a]-pyrene, at concentrations
      representative of human exposure, in an isolated rat follicle culture assay.
AB  - BACKGROUND: The adverse effects of cigarette smoking on human fertility have been
      well documented. However, the mechanism(s) underlying the detrimental effects of
      cigarette smoking are unknown. Using a novel isolated rat follicle culture assay,
      we tested the hypothesis that benzo-[a]-pyrene (B[a]P), a constituent of
      cigarette smoke, can inhibit follicle growth. METHODS: B[a]P levels were
      quantified in the serum and follicular fluid (FF) of women undergoing in vitro
      fertilization (IVF) treatment exposed to mainstream smoke (n = 19) and non
      smokers (n = 10) by gas chromatography mass spectrometry. Isolated rat follicles
      were cultured with increasing concentrations of B[a]P (1.5-300 ng ml(-1)) and
      follicle diameter was measured daily. RESULTS: Mean ( +/- Standard error of the
      mean) B[a]P) was quantified in the serum (0.40 +/- 0.13 ng ml(-1)) and FF (1.32
      +/- 0.68 ng ml(-1)) of women who smoke. IVF stimulation and outcome measures were
      similar between female smokers and non-smokers with the exception of implantation
      rate and pregnancy rate, which were both significantly lower (P < 0.05) in the MS
      group. B[a]P treatment significantly reduced rat follicle diameter and attenuated
      FSH stimulated growth in a dose-dependent manner, beginning at 1.5 ng ml(-1).
      CONCLUSIONS: Our data suggest that B[a]P, at levels representative of those
      measured in human FF, may adversely affect follicle development and be an ovarian
      toxicant.

PMID- 17218371
TI  - Dual effect of thapsigargin on cell death in porcine aortic smooth muscle cells.
AB  - A sustained increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)) can
      cause cell death. In this study, we found that, in cultured porcine aortic smooth
      muscle cells, endoplasmic reticulum (ER) stress, triggered by depletion of Ca(2+)
      stores by thapsigargin (TG), induced an increase in the [Ca(2+)](i) and cell
      death. However, the TG-induced death was not related to the [Ca(2+)](i) increase
      but was mediated by targeting of activated Bax to mitochondria and the opening of
      mitochondrial permeability transition pores (PTPs). Once the mitochondrial PTPs
      had opened, several events, including collapse of the mitochondrial membrane
      potential, cytochrome c release, and caspase-3 activation, occurred and the cells
      died. TG-induced cell death was completely inhibited by the pan-caspase inhibitor
      Z-VAD-fmk and was enhanced by the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid (BAPTA), suggesting the existence of a Ca(2+)
      dependent anti-apoptotic mechanism. After TG treatment, Ca(2+)-sensitive mitogen
      activated protein kinase (MAPK) activation was induced and acted as a downstream
      effector of phosphatidylinositol 3-kinase (PI 3-kinase). The protective effect of
      Z-VAD-fmk on TG-induced cell death was reversed by BAPTA, PD-098059 (an MAPK
      kinase inhibitor), or LY-294002 (a PI 3-kinase inhibitor). Taken together, our
      data indicate that ER stress simultaneously activate two pathways, the
      mitochondrial caspase-dependent death cascade and the Ca(2+)-dependent PI 3
      kinase/MAPK anti-apoptotic machinery. The Bax activation and translocation, but
      not the [Ca(2+)](i) increase, may activate mitochondrial PTPs, which, in turn,
      causes activation of caspases and cell death, whereas Ca(2+)-dependent MAPK
      activation counteracts death signaling; removal of Ca(2+) activated a second
      caspase-independent death pathway.

PMID- 17218372
TI  - Atrophy, but not necrosis, in rabbit skeletal muscle denervated for periods up to
      one year.
AB  - Our understanding of the effects of long-term denervation on skeletal muscle is
      heavily influenced by an extensive literature based on the rat. We have studied
      physiological and morphological changes in an alternative model, the rabbit. In
      adult rabbits, tibialis anterior muscles were denervated unilaterally by
      selective section of motor branches of the common peroneal nerve and examined
      after 10, 36, or 51 wk. Denervation reduced muscle mass and cross-sectional area
      by 50-60% and tetanic force by 75%, with no apparent reduction in specific force
      (force per cross-sectional area of muscle fibers). The loss of mass was
      associated with atrophy of fast fibers and an increase in fibrous and adipose
      connective tissue; the diameter of slow fibers was preserved. Within fibers,
      electron microscopy revealed signs of ultrastructural disorganization of
      sarcomeres and tubular systems. This, rather than the observed transformation of
      fiber type from IIx to IIa, was probably responsible for the slow contractile
      speed of the muscles. The muscle groups denervated for 10, 36, or 51 wk showed no
      significant differences. At no stage was there any evidence of necrosis or
      regeneration, and the total number of fibers remained constant. These changes are
      in marked contrast to the necrotic degeneration and progressive decline in mass
      and force that have previously been found in long-term denervated rat muscles.
      The rabbit may be a better choice for a model of the effects of denervation in
      humans, at least up to 1 yr after lesion.

PMID- 17218374
TI  - Premedication with controlled-release oxycodone does not improve management of
      postoperative pain after day-case gynaecological laparoscopic surgery.
AB  - BACKGROUND: Controlled-release (CR) oxycodone provides an option for the
      prevention of postoperative pain. We designed this randomized double-blinded
      placebo controlled study to evaluate the control of pain after premedication with
      CR oxycodone 15 mg in addition to ibuprofen 800 mg orally in day-case
      gynaecological laparoscopic surgery. METHODS: Sixty consenting patients were
      anaesthetized in a standardized fashion. Postoperative analgesia was provided by
      ibuprofen 800 mg twice a day in combination with fentanyl i.v. in the recovery
      room and normal-release (NR) oxycodone orally after the recovery room. The visual
      analogue scale (VAS) scores for pain and side-effects, and the amounts of
      postoperative analgesics were recorded for 24 h after discharge from the
      hospital. After a statistical analysis of the original study, we extended the
      study to investigate another 10 patients, who received CR oxycodone 15 mg orally
      in an open-labelled fashion 60 min before surgery. The plasma concentrations of
      oxycodone were measured from samples drawn before and 2, 4, 6 and 8 h after
      premedication. RESULTS: The amounts of fentanyl [100 microg (0-330) in the CR
      oxycodone group; 125 microg (0-330) in the placebo group], NR oxycodone, or the
      VAS scores for pain during the first 24 h after the discharge from the hospital
      did not differ after the premedication with CR oxycodone or placebo. In the
      extension study group, the peak plasma concentration (C(max)) of oxycodone was
      10.0 (4.6-14.7) ng ml(-1), indicating possibly a sub-therapeutic level.
      CONCLUSION: Oral premedication with CR oxycodone did not improve management of
      postoperative pain after day-case gynaecological laparoscopic surgery.

PMID- 17218375
TI  - Semi-invasive monitoring of cardiac output by a new device using arterial
      pressure waveform analysis: a comparison with intermittent pulmonary artery
      thermodilution in patients undergoing cardiac surgery.
AB  - BACKGROUND: Thermodilution technique using a pulmonary artery catheter (PAC) is a
      widely used method to determine cardiac output (CO). It is increasingly
      criticized because of its invasiveness and its unclear risk-benefit ratio. Thus,
      less invasive techniques for measuring CO are highly desirable. We compared a
      new, semi-invasive device (FloTrac/Vigileo) using arterial pressure waveform
      analysis for CO measurement in patients undergoing cardiac surgery with bolus
      thermodilution measurements. METHODS: Forty patients undergoing coronary artery
      bypass grafting or valve repair were enrolled. A PAC was inserted and routine
      radial arterial access was used for semi-invasive determination of CO with the
      Vigileo. CO was measured simultaneously by bolus thermodilution and the Vigileo
      technique after induction of anaesthesia (T1), before cardiopulmonary bypass
      (CPB) (T2), after CPB (T3), after sternal closure (T4), on arrival in the
      intensive care unit (ICU) (T5), and 4 h (T6), 8 h (T7), and 24 h after surgery
      (T8). CO was indexed to the body surface area (cardiac index, CI). RESULTS: A
      total of 244 pairs of CI measurements were analysed. Bias and precision (1.96 sd
      of the bias) were 0.46 litre min(-1) m(-2) and +/- 1.15 litre min(-1) m(-2) (r =
      0.53) resulting in an overall percentage error of 46%. Subgroup analysis revealed
      a percentage error of 51% for data pairs obtained intraoperatively (T1-T4), 42%
      in ICU (T5-T8), and 56% for values obtained during low CI (T1-T8). CONCLUSIONS:
      In cardiac surgery patients, CO measured by a new semi-invasive arterial pressure
      waveform analysis device showed only moderate agreement with intermittent
      pulmonary artery thermodilution measurement.

PMID- 17218376
TI  - Teletherapeutic drug administration by long distance closed-loop control of
      propofol.
AB  - BACKGROUND: The objective of this pilot study was to investigate the feasibility
      of an EEG-controlled closed-loop administration of propofol over a long distance
      of about 200 km. METHODS: We performed a teletherapeutic propofol infusion during
      total intravenous anaesthesia with propofol in 11 patients undergoing general
      surgery. The teletherapeutic system consisted of a computer at the patient site
      in Munich and a computer at the control site in Erlangen, which were connected
      via the internet through a virtual private network. The patient's EEG signal was
      sent to the control site computer, where the median frequency (MEF) of the EEG
      power spectrum was calculated. The propofol infusion, determined by a model-based
      adaptive feedback algorithm to maintain a MEF of 1.5 to 2 Hz, was sent to the
      patient site computer connected to the infusion pump. The quality of the control
      was assessed by the performance error defined as the percentage deviation of the
      measured MEF from the set point and the necessity of interventions by the
      anaesthetist at the patient site. RESULTS: During closed-loop administration of
      propofol [83 (52) min] the median performance error of the system was - 4.6
      (4.4)% and the median absolute performance error was 18.8 (5.7)%. From a total
      number of 10 905 transmitted EEG epochs, there were five epochs with transmission
      errors, without further consequences for drug control. In one patient,
      teletherapy was stopped because the internet connection was interrupted.
      CONCLUSIONS: Teletherapeutic drug administration could be realized over a longer
      distance. Further studies have to investigate the practicability and safety of
      teletherapeutic drug control in anaesthesia.

PMID- 17218377
TI  - Stereoselective pharmacokinetics of ketamine and norketamine after racemic
      ketamine or S-ketamine administration during isoflurane anaesthesia in Shetland
      ponies.
AB  - BACKGROUND: The arterial pharmacokinetics of ketamine and norketamine enantiomers
      after racemic ketamine or S-ketamine i.v. administration were evaluated in seven
      gelding ponies in a crossover study (2-month interval). METHODS: Anaesthesia was
      induced with isoflurane in oxygen via a face-mask and then maintained at each
      pony's individual MAC. Racemic ketamine (2.2 mg kg(-1)) or S-ketamine (1.1 mg kg(
      1)) was injected in the right jugular vein. Blood samples were collected from the
      right carotid artery before and at 1, 2, 4, 8, 16, 32, 64, and 128 min after
      ketamine administration. Ketamine and norketamine enantiomer plasma
      concentrations were determined by capillary electrophoresis. Individual R
      ketamine and S-ketamine concentration vs time curves were analysed by non-linear
      least square regression two-compartment model analysis using PCNonlin. Plasma
      disposition curves for R-norketamine and S-norketamine were described by
      estimating AUC, C(max), and T(max). Pulse rate (PR), respiratory rate (R(f)),
      tidal volume (V(T)), minute volume ventilation (V(E)), end-tidal partial pressure
      of carbon dioxide (PE'(CO(2))), and mean arterial blood pressure (MAP) were also
      evaluated. RESULTS: The pharmacokinetic parameters of S- and R-ketamine
      administered in the racemic mixture or S-ketamine administered separately did not
      differ significantly. Statistically significant higher AUC and C(max) were found
      for S-norketamine compared with R-norketamine in the racemic group. Overall,
      R(f), V(E), PE'(CO(2)), and MAP were significantly higher in the racemic group,
      whereas PR was higher in the S-ketamine group. CONCLUSIONS: Norketamine
      enantiomers showed different pharmacokinetic profiles after single i.v.
      administration of racemic ketamine in ponies anaesthetised with isoflurane in
      oxygen (1 MAC). Cardiopulmonary variables require further investigation.

PMID- 17218378
TI  - Effects of epidural anaesthesia on surgical stress-induced immunosuppression
      during upper abdominal surgery.
AB  - BACKGROUND: Previously, we have demonstrated that surgical stress rapidly induced
      transient hyporesponsiveness of blood cells to endotoxin and that monocyte mCD14
      and HLA-DR expression decreased soon after the start of surgery under general
      anaesthesia. This study was designed to investigate the effects of epidural
      anaesthesia on surgical stress-induced immunosuppression in patients undergoing
      upper abdominal surgery. METHODS: After having obtained informed consent,
      patients were randomly allocated to receive general anaesthesia (Group G) or
      general anaesthesia with epidural anaesthesia (Group E). Perioperative changes in
      neutrophil phagocytic activity, neutrophil respiratory burst activity, monocyte
      mCD14 and HLA-DR expression, plasma IL-10 concentration, and the LPS-induced TNF
      alpha production in whole blood were measured. RESULTS: Surgical stress rapidly
      depressed neutrophil phagocytic activity, monocyte mCD14 and HLA-DR expression,
      and LPS-induced TNF-alpha production ex vivo (P < 0.05 vs preoperation) in both
      Group G and Group E. In contrast, the plasma IL-10 concentration increased
      significantly 2 h after the start of surgery (P < 0.05) in both groups. There
      were no significant differences between the two groups. The neutrophil
      respiratory burst activity did not change during the operation in either group.
      CONCLUSION: This study showed that the innate immune system is suppressed from
      the early period of upper abdominal surgery. Subgroup analysis suggested that
      epidural anaesthesia to T4 dermatome as well as general anaesthesia may not
      protect patients from this immunosuppression. These results in part explain the
      impairment of host-defense mechanisms seen in the perioperative period.

PMID- 17218379
TI  - Recombinant versus plasma-derived factor VIII products and the development of
      inhibitors in previously untreated patients with severe hemophilia A: the CANAL
      cohort study.
AB  - It has been suggested that plasma-derived factor VIII products induce fewer
      inhibitors than recombinant factor VIII products. We investigated the
      relationship of factor VIII product type and switching between factor VIII
      products with the risk to develop inhibitors. This multicenter retrospective
      cohort study included 316 patients with severe hemophilia A born between 1990 and
      2000. The outcome was clinically relevant inhibitor development, defined as the
      occurrence of at least 2 positive inhibitor titers with decreased recovery. The
      risk of inhibitor development was not clearly lower in plasma-derived compared
      with recombinant factor VIII products (relative risk [RR], 0.8; 95% confidence
      interval [CI], 0.5-1.3). Among high-titer inhibitors, the possible reduction in
      risk was even less pronounced (RR, 0.9; CI, 0.5-1.5). Plasma-derived products
      with considerable quantities of von Willebrand factor (VWF) carried the same risk
      for inhibitor development as recombinant factor VIII products (RR, 1.0; CI, 0.6
      1.6). Switching between factor VIII products did not increase the risk for
      inhibitors (RR, 1.1; CI, 0.6-1.8). In conclusion, our findings support neither
      the notion that plasma-derived factor VIII products with considerable
      concentrations of VWF confer a lower risk to develop inhibitory antibodies than
      recombinant factor VIII products, nor that switching between factor VIII product
      brands increases inhibitor risks in previously untreated patients with severe
      hemophilia A.

PMID- 17218380
TI  - Genomewide identification of prednisolone-responsive genes in acute lymphoblastic
      leukemia cells.
AB  - Glucocorticoids are keystone drugs in the treatment of childhood acute
      lymphoblastic leukemia (ALL). To get more insight in signal transduction pathways
      involved in glucocorticoid-induced apoptosis, Affymetrix U133A GeneChips were
      used to identify transcriptionally regulated genes on 3 and 8 hours of
      prednisolone exposure in leukemic cells of 13 children as compared with
      nonexposed cells. Following 3 hours of exposure no significant changes in gene
      expression could be identified. Following 8 hours of exposure, 51 genes were
      differentially expressed (P < .001 and false discovery rate < 10%) with 39 genes
      being up-regulated (median, 2.4-fold) and 12 genes were down-regulated (median,
      1.7-fold). Twenty-one of those genes have not been identified before to be
      transcriptionally regulated by prednisolone. Two of the 3 most highly up
      regulated genes were tumor suppressor genes, that is, thioredoxin-interacting
      protein (TXNIP; 3.7-fold) and zinc finger and BTB domain containing 16 (ZBTB16;
      8.8-fold). About 50% of the differentially expressed genes were functionally
      categorized in 3 major routes, namely MAPK pathways (9 genes), NF-kappaB
      signaling (11 genes), and carbohydrate metabolism (5 genes). Biologic
      characterization of these genes and pathways might elucidate the action of
      glucocorticoids in ALL cells, possibly suggesting causes of glucocorticoid
      resistance and new potential targets for therapy.

PMID- 17218381
TI  - Reciprocal regulation of human natural killer cells and macrophages associated
      with distinct immune synapses.
AB  - Natural killer (NK) cells directly lyse tumor or viral-infected cells but also an
      important role for NK cell cytotoxicity in regulating the extent of immune
      responses is emerging. Here, we show that autologous human macrophages activated
      NK cell proliferation and cytokine secretion, increased expression of activating
      receptors, and primed NK cell cytotoxicity against susceptible target cells.
      Ligation of NK cell 2B4, and not NKp30 (known to be important for DC-mediated NK
      cell activation), is critical for this macrophage-mediated NK cell activation.
      Reciprocally, however, NK cells regulated macrophage activity by directly killing
      macrophages stimulated by high doses of LPS. Cytolysis was triggered by NKG2D
      recognition of stress-inducible class I major histocompatibility complex (MHC)
      like ligands on macrophages: high doses of LPS induced transcription and surface
      expression of ULBP1, ULBP2, and ULBP3 and surface expression of constitutively
      transcribed MICA. Thus, these data suggest a new function for NK cell
      cytotoxicity in eliminating overstimulated macrophages. Additionally, these
      interactions define, for the first time, 2 distinct activating NK cell synapses:
      lytic and nonlytic. Triggering NK cell proliferation and cytokine secretion, but
      not cytolysis, specifically associated with synaptic accumulation of macrophage F
      actin and NK cell 2B4, while macrophages were killed when NK cell F-actin and
      macrophage ICAM-1 accumulated around a central cluster of NK cell NKG2D/DAP10.

PMID- 17218382
TI  - PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a
      differentially regulated mechanism of secretion.
AB  - PF-4/CXCL4 is a member of the CXC chemokine family, which is mainly produced by
      platelets and known for its pleiotropic biological functions. Recently, the
      proteic product of a nonallelic variant gene of CXCL4 was isolated from human
      platelets and named as CXCL4L1. CXCL4L1 shows only 4.3% amino acid divergence in
      the mature protein, but exhibits a 38% amino acid divergence in the signal
      peptide region. We hypothesized that this may imply a difference in the cell type
      in which CXCL4L1 is expressed or a difference in its mode of secretion. In
      different types of transfected cells, CXCL4 and CXCL4L1 exhibited a distinct
      subcellular localization and a differential regulation of secretion, CXCL4 being
      stored in secretory granules and released in response to protein kinase C
      activation, whereas CXCL4L1 was continuously synthesized and secreted through a
      constitutive pathway. A protein kinase C-regulated CXCL4 secretion was observed
      also in lymphocytes, a cell type expressing mainly CXCL4 mRNA, whereas smooth
      muscle cells, which preferentially expressed CXCL4L1, exhibited a constitutive
      pathway of secretion. These results demonstrate that CXCL4 and CXCL4L1 exhibit a
      distinct subcellular localization and are secreted in a differentially regulated
      manner, suggesting distinct roles in inflammatory or homeostatic processes.

PMID- 17218383
TI  - Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of
      inflammation.
AB  - The anemia of inflammation is an acquired disorder affecting patients with a
      variety of medical conditions, and it is characterized by changes in iron
      homeostasis and erythropoiesis. Mounting evidence suggests that hepcidin
      antimicrobial peptide plays a primary role in the pathogenesis of the anemia of
      inflammation. To evaluate which features of this anemia can be attributed to
      hepcidin, we have generated mice carrying a tetracycline-regulated hepcidin
      transgene. Expression of the hepcidin transgene resulted in down-regulation of
      endogenous hepcidin mRNA. The transgenic mice developed a mild-to-moderate anemia
      associated with iron deficiency and iron-restricted erythropoiesis. Similar to
      the anemia of inflammation, iron accumulated in tissue macrophages, whereas a
      relative paucity of iron was found in the liver. Circulating erythrocytes in
      transgenic animals had normal survival rates, but transgenic animals had an
      impaired response to erythropoietin. Thus, hepcidin transgenic mice recapitulate
      each of the key features of anemia of inflammation in human patients and serve as
      a useful model of this prevalent disorder.

PMID- 17218384
TI  - Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26
      cytochrome metabolism in differential all-trans retinoic acid sensitivity.
AB  - Disease relapse sometimes occurs after acute promyelocytic leukemia (APL) therapy
      with all-trans retinoic acid (ATRA). Among the diagnostic parameters predicting
      relapse, heterogeneity in the in vitro differentiation rate of blasts is an
      independent factor. To identify biologic networks involved in resistance, we
      conducted pharmacogenomic studies in APL blasts displaying distinct ATRA
      sensitivities. Although the expression profiles of genes invested in
      differentiation were similarly modulated in low- and high-sensitive blasts, low
      sensitive cells showed higher levels of transcription of ATRA-target genes,
      transcriptional regulators, chromatin remodelers, and transcription factors. In
      opposition, only high-sensitive blasts expressed the CYP26A1 gene, encoding the
      p450 cytochrome which is known to be involved in retinoic acid catabolism. In NB4
      cells, ATRA treatment activates a novel signaling pathway, whereby interleukin-8
      stimulates the expression of the homeobox transcription factor HOXA10v2, an
      effective enhancer of CYP26A1 transcription. These data were corroborated in
      primary APL cells, as maturation levels correlated with CYP26A1 expression.
      Treatment with a retinoic acid metabolism blocking agent (RAMBA) results in high
      nucleoplasmic concentrations of retinoid and growth of NB4-resistant subclones.
      Hence, for APL blasts associated with poor prognosis, the low CYP26A1 expression
      may explain high risk of resistance installation, by increased retinoid pressure.
      Pharmacogenomic profiles of genes involved in retinoid acid metabolism may help
      to optimize anticancer therapies, including retinoids.

PMID- 17218387
TI  - Ectopic expression of PAX5 promotes maintenance of biphenotypic myeloid
      progenitors coexpressing myeloid and B-cell lineage-associated genes.
AB  - The transcription factor PAX5 is a critical regulator of B-cell commitment and
      development. Although normally not expressed in myeloid progenitors, PAX5 has
      recently been shown to be frequently expressed in myeloid malignancies and to
      suppress expression of myeloid differentiation genes, compatible with an effect
      on the differentiation or maintenance of myeloid progenitors. However, previous
      studies in which PAX5 was ectopically expressed in normal myeloid progenitors in
      vivo and in vitro provided conflicting results as to the effect of PAX5 on
      myeloid development. Herein, we demonstrate that on ectopic expression of PAX5 in
      bone marrow multipotent stem/progenitor cells, cells with a biphenotypic
      B220(+)GR-1/MAC-1(+) phenotype are produced. These remain cytokine-dependent, but
      unlike control-transduced cells they sustain long-term generation of myeloid
      progenitors in vitro and remain capable of myeloid differentiation. Notably,
      PAX5(+)B220(+)GR-1/MAC-1(+) myeloid progenitors coexpress, at the single-cell
      level, myeloid genes and otherwise B-cell-specific PAX5 target genes. These
      findings establish that ectopic expression of PAX5 introduces extensive self
      renewal properties in otherwise short-lived myeloid progenitors. Along with the
      established ectopic expression of PAX5 in acute myeloid leukemia, this motivates
      a careful investigation of the potential involvement of ectopic PAX5 expression
      in myeloid and biphenotypic leukemias.

PMID- 17218386
TI  - Myeloproliferative disease induced by TEL-PDGFRB displays dynamic range
      sensitivity to Stat5 gene dosage.
AB  - Expression of the constitutively activated TEL/PDGFbetaR fusion protein is
      associated with the t(5;12)(q33;p13) chromosomal translocation found in a subset
      of patients with chronic myelomonocytic leukemia. TEL/PDGFbetaR activates
      multiple signal transduction pathways in cell-culture systems, and expression of
      the TEL-PDGFRB fusion gene induces myeloproliferative disease (MPD) in mice. We
      used gene-targeted mice to characterize the contribution of signal transducer and
      activator of transcription (Stat) and Src family genes to TEL-PDGFRB-mediated
      transformation in methylcellulose colony and murine bone marrow
      transduction/transplantation assays. Fetal liver hematopoietic stem and
      progenitor cells harboring targeted deletion of both Stat5a and Stat5b
      (Stat5ab(null/null)) genes were refractory to transformation by TEL-PDGFRB in
      methylcellulose colony assays. Notably, these cell populations were maintained in
      Stat5ab(null/null) fetal livers and succumbed to transformation by c-Myc.
      Surprisingly, targeted disruption of either Stat5a or Stat5b alone also impaired
      TEL-PDGFRB-mediated transformation. Survival of TPiGFP-->Stat5a(-/-) and TPiGFP-
      >Stat5a(+/-) mice was significantly prolonged, demonstrating significant
      sensitivity of TEL-PDGFRB-induced MPD to the dosage of Stat5a. TEL-PDGFRB
      mediated MPD was incompletely penetrant in TPiGFP-->Stat5b(-/-) mice. In
      contrast, Src family kinases Lyn, Hck, and Fgr and the Stat family member Stat1
      were dispensable for TEL-PDGFRB disease. Together, these data demonstrate that
      Stat5a and Stat5b are dose-limiting mediators of TEL-PDGFRB-induced
      myeloproliferation.

PMID- 17218388
TI  - TLR ligands differentially affect uptake and presentation of cellular antigens.
AB  - Dendritic cells (DCs) have the unique ability to efficiently present T-cell
      epitopes from exogenous antigens on MHC class I molecules, a process called cross
      presentation. In our study we demonstrate that stimulation of monocyte-derived
      DCs with Toll-like receptor (TLR) ligands differentially affects the uptake and
      cross-presentation of cellular antigens. Activation of DCs with TLR3 or TLR4 but
      not with TLR2 or TLR7/8 ligands inhibited phagocytosis of apoptotic tumor cells
      and resulted in a reduced cross-presentation of pp65-derived T-cell epitopes on
      MHC class I molecules upon engulfment of cytomegalovirus (CMV)-infected
      fibroblasts. These results have an important impact on the understanding of the
      interactions between the immune system and pathogens and the development of
      vaccination strategies to treat malignant diseases.

PMID- 17218385
TI  - MEK1/2 inhibitors sensitize Bcr/Abl+ human leukemia cells to the dual Abl/Src
      inhibitor BMS-354/825.
AB  - Interactions between MEK1/2 inhibitors and the dual Abl/Src kinase inhibitor
      dasatinib (BMS-354825) were examined in chronic myeloid leukemia (CML) cell lines
      and primary specimens. Cotreatment of K562 or LAMA cells with subtoxic or
      marginally toxic concentrations of PD184352 (or U0126) and dasatinib
      synergistically potentiated mitochondrial damage, caspase activation, and
      apoptosis. Similar interactions were observed in CD34(+) cells from one CML
      patient-derived but not in a normal human CD34(+) bone marrow cell specimen.
      These interactions were associated with multiple perturbations in survival
      signaling pathways, including inactivation of Bcr/Abl, STAT5, and ERK1/2; down
      regulation of Bcl-x(L) and Mcl-1; and dephosphorylation/activation of Bim. They
      were also associated with BAX/BAK conformational change, mitochondrial
      dysfunction, and caspase activation. Bim knockdown by shRNA suppressed BAX and
      BAK conformational change and protected cells from dasatinib/PD184352 lethality.
      Conversely, K562 cells ectopically expressing Mcl-1 or Bcl-x(L) were
      significantly less susceptible to dasatinib/PD184352 toxicity. Notably, the
      dasatinib/PD184352 regimen was active against leukemic cells exhibiting various
      forms of imatinib mesylate resistance, including Bcr/Abl overexpression, Lyn
      activation, and several Bcr/Abl kinase domain mutations (eg, E255K, M351T), but
      not T315I. Together, these findings suggest that strategies combining dasatanib
      with MEK1/2 inhibitors warrant further investigation in Bcr/Abl(+) malignancies,
      particularly in the setting of imatinib mesylate-resistant disease.

PMID- 17218389
TI  - Sarcoidosis presenting with tachy- and brady-arrhythmias.
AB  - We describe a case report of a 49-year-old man admitted to a cardiology unit with
      a series of arrhythmias with no initially obvious aetiology. Further assessment
      and the use of cardiac magnetic resonance imaging and histology allowed a
      diagnosis of cardiac sarcoidosis to be made. Cardiac sarcoidosis is a major cause
      of death in patients with systemic sarcoidosis. Cardiac magnetic resonance
      imaging is an additional diagnostic tool for this condition without ionizing
      radiation exposure.

PMID- 17218390
TI  - Spectral pulsed-wave tissue Doppler imaging lateral-to-septal delay fails to
      predict clinical or echocardiographic outcome after cardiac resynchronization
      therapy.
AB  - AIMS: The current study sought to assess if pre-implantation lateral-to-septal
      delay (LSD) > or =60 ms assessed by spectral pulsed-wave myocardial tissue
      Doppler imaging (PW-TDI) could predict successful long-term outcome after cardiac
      resynchronization therapy (CRT). METHODS AND RESULTS: Sixty patients (72% males,
      mean age 59 +/- 10 years) who were referred for CRT according to the ACC/ESC
      guidelines were enrolled in the study. All patients underwent spectral PW-TDI
      before and 1 year after CRT. Two left ventricular (LV) dyssynchrony time
      intervals, T(O) and T(P) (time to onset and peak of LV myocardial velocity,
      respectively), LSD were recorded. Left ventricular dyssynchrony was defined as
      LSD > or =60 ms. Clinical response was defined as an improvement in >1 NYHA class
      plus improvement in 6-min walk distance (6MWD) > or =25%, echocardiographic
      response was defined as a > or =15% reduction in LV end-systolic volume (LV-ESV).
      One year after CRT, 50 patients (83%) were clinical responders and 47 patients
      (78%) were echocardiographic responders. Both T(O) and T(P) LV dyssynchrony
      indices failed to predict echocardiographic CRT outcome. In addition, there were
      no significant differences between 'synchronous' and 'dyssynchronous' patient
      populations at baseline or follow-up in either clinical (NYHA class and 6MWD) or
      echocardiographic (LV ejection fraction, LV end-diastolic, and end-systolic)
      variables. CONCLUSION: The great majority of patients referred for CRT benefit
      clinically from it. However, spectral PW-TDI failed to predict CRT outcome. When
      PW-TDI dyssynchrony was applied for selection of proper CRT patients, up to 80
      86% of the patients with synchronous LSD that had proven clinical and
      echocardiographic benefit from CRT would have been denied CRT.

PMID- 17218393
TI  - Chronic myeloid leukemia blast crisis arises from progenitors.
AB  - Chronic myeloid leukemia (CML) progresses through three distinct clinical stages:
      chronic phase, accelerated phase, and blast crisis. The progression to
      accelerated phase and blast crisis is driven by activation of oncogenes,
      inactivation of tumor suppressor genes, and/or amplification of the BCR-ABL
      fusion gene, which causes the chronic phase of the disease. The cell of origin of
      blast crisis is a subject of speculation. Here, I develop a simple mathematical
      model of CML blast crisis to investigate whether blasts arise from leukemic stem
      cells or more differentiated leukemic cells. I use data of patients treated with
      imatinib and previous agents to estimate the effects of therapy on the rate of
      progression. Imatinib reduces the progression rate 10-fold as compared with
      previous (ineffective) therapies. If blasts were produced by leukemic stem cells,
      there would be no difference in the rate of progression between patients treated
      with imatinib and previous therapies, because imatinib seems to be incapable of
      depleting leukemic stem cells. Imatinib does, however, deplete leukemic
      progenitors. Therefore, CML blasts are likely to arise from leukemic progenitors.
      Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 17218392
TI  - Erasure of cellular memory by fusion with pluripotent cells.
AB  - Pluripotent cells have been suggested as a prime source to reprogram somatic
      cells. We used F9 EC cells as a pluripotent partner to reprogram neurosphere
      cells (NSCs) because they exhibit a nonneural differentiation potential in the
      presence of retinoic acid. F9-NSC hybrid cells displayed various features of
      reprogramming, such as reactivation of pluripotency genes, inactivation of tissue
      specific genes, and reactivation of the inactive X chromosome. As the hybrid
      cells undergo differentiation, the pluripotency markers Oct4 and Nanog were
      downregulated. Whereas neural marker genes were not upregulated, endodermal and
      mesodermal markers were, suggesting that NSCs lose memory of their neural origin
      and preferentially differentiate to the lineages corresponding to the F9 program.
      After fusion, the methylation status in the Xist region was similar to that of F9
      EC cells. However, upon differentiation, the Xist region failed to resume the
      methylation patterns of differentiated cells, suggesting that the Xist in F9-NSC
      hybrids does not easily acquire a differentiated state.

PMID- 17218395
TI  - Concise review: regulation of embryonic stem cell lineage commitment by mitogen
      activated protein kinases.
AB  - Embryonic stem (ES) cells can give rise, in vivo, to the ectodermal, endodermal,
      and mesodermal germ layers and, in vitro, can differentiate into multiple cell
      lineages, offering broad perspectives in regenerative medicine. Understanding the
      molecular mechanisms governing ES cell commitment is an essential challenge in
      this field. The mitogen-activated protein kinase (MAPK) pathways extracellular
      signal-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and p38MAPK are
      able to regulate ES commitment from early steps of the process to mature
      differentiated cells. Whereas the ERK pathway inhibits the self-renewal of ES
      cells, upon commitment this pathway is involved in the development of
      extraembryonic tissues, in early mesoderm differentiation, and in the formation
      of mature adipocytes; p38MAPK displays a large spectrum of action from neurons to
      adipocytes, and JNK is involved in both ectoderm and primitive endoderm
      differentiations. Furthermore, for a given pathway, several of these effects are
      isoform-dependent, revealing the complexity of the cellular response to
      activation of MAPK pathways. Regarding tissue regeneration, the potential outcome
      of systematic analysis of the function of different MAPKs in different ES cell
      differentiation programs is discussed. Disclosure of potential conflicts of
      interest is found at the end of this article.

PMID- 17218394
TI  - Transcription profiling of adult and fetal human neuroprogenitors identifies
      divergent paths to maintain the neuroprogenitor cell state.
AB  - Global gene expression profiling was performed using RNA from adult human
      hippocampus-derived neuroprogenitor cells (NPCs) and multipotent frontal cortical
      fetal NPCs compared with adult human mesenchymal stem cells (hMSCs) as a
      multipotent adult stem cell control, and adult human hippocampal tissue, to
      define a gene expression pattern that is specific for human NPCs. The results
      were compared with data from various databases. Hierarchical cluster analysis of
      all neuroectodermal cell/tissue types revealed a strong relationship of adult
      hippocampal NPCs with various white matter tissues, whereas fetal NPCs strongly
      correlate with fetal brain tissue. However, adult and fetal NPCs share the
      expression of a variety of genes known to be related to signal transduction, cell
      metabolism and neuroectodermal tissue. In contrast, adult NPCs and hMSCs overlap
      in the expression of genes mainly involved in extracellular matrix biology. We
      present for the first time a detailed transcriptome analysis of human adult NPCs
      suggesting a relationship between hippocampal NPCs and white matter-derived
      precursor cells. We further provide a framework for standardized comparative gene
      expression analysis of human brain-derived NPCs with other stem cell populations
      or differentiated tissues. Disclosure of potential conflicts of interest is found
      at the end of this article.

PMID- 17218396
TI  - Long-term culture of postnatal mouse hepatic stem/progenitor cells and their
      relative developmental hierarchy.
AB  - Few studies on the long-term culture of postnatal mouse hepatic stem/progenitor
      cells have been reported. We successfully adapted a serum-free culture system
      that we employed previously to expand fetal mouse hepatic stem/progenitor cells
      and maintained them in culture over long periods. The expanded postnatal cells
      contained immature alpha-fetoprotein-positive cells along with hepatocytic and
      cholangiocytic lineage-committed cells. These cells expressed CD49f but not CD45,
      CD34, Thy-1, c-kit, CD31, or flk-1, and oncostatin M induced their
      differentiation. This heterogeneous population contained side population (SP)
      cells, which express the ATP-binding cassette transporter ABCG2, and sca-1+
      cells. As mice aged, the frequency of SP and sca-1+ cells decreased along with
      the ability of cultured cells to expand. Approximately 20%-40% of the SP cells
      expressed sca-1, but only a few sca-1+ cells were also SP cells. Analysis of
      colonies derived from single SP or sca-1+ cells revealed that, although both
      cells had dual differentiation potential and self-renewal ability, SP cells
      formed colonies more efficiently and gave rise to SP and sca-1+ cells, whereas
      sca-1+ cells generated only sca-1+ progeny. Thus, SP cells are more
      characteristic of stem cells than are sca-1+ cells. In regenerating livers,
      ABCG2+ cells and sca-1+ cells were detected around or in the portal area (the
      putative hepatic stem cell niche). The expanded cells share many features of
      fetal hepatic stem/progenitor cells or oval cells and may be useful in
      determining the mechanisms whereby hepatic stem cells self-renew and
      differentiate.

PMID- 17218397
TI  - Progenitor cells from the porcine neural retina express photoreceptor markers
      after transplantation to the subretinal space of allorecipients.
AB  - Work in rodents has shown that cultured retinal progenitor cells (RPCs) integrate
      into the degenerating retina, thus suggesting a potential strategy for treatment
      of similar degenerative conditions in humans. To demonstrate the relevance of the
      rodent work to large animals, we derived progenitor cells from the neural retina
      of the domestic pig and transplanted them to the laser-injured retina of
      allorecipients. Prior to grafting, immunocytochemical analysis showed that
      cultured porcine RPCs widely expressed neural cell adhesion molecule, as well as
      markers consistent with immature neural cells, including nestin, Sox2, and
      vimentin. Subpopulations expressed the neurodevelopmental markers CD-15,
      doublecortin, beta-III tubulin, and glial fibrillary acidic protein. Retina
      specific markers expressed included the bipolar marker protein kinase Calpha and
      the photoreceptor-associated markers recoverin and rhodopsin. In addition,
      reverse transcription-polymerase chain reaction showed expression of the
      transcription factors Dach1, Hes1, Lhx2, Pax6, Six3, and Six6. Progenitor cells
      prelabeled with vital dyes survived as allografts in the subretinal space for up
      to 5 weeks (11 of 12 recipients) without exogenous immune suppression. Grafted
      cells expressed transducin, recoverin, and rhodopsin in the pig subretinal space,
      suggestive of differentiation into photoreceptors or, in a few cases, migrated
      into the neural retina and extended processes, the latter typically showing
      radial orientation. These results demonstrate that many of the findings seen with
      rodent RPCs can be duplicated in a large mammal. The pig offers a number of
      advantages over mice and rats, particularly in terms of functional testing and
      evaluation of the potential for clinical translation to human subjects.
      Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 17218398
TI  - Analysis of the origin and population dynamics of cardiac progenitor cells in a
      donor heart model.
AB  - Cardiac progenitor (stem) cells have recently been detected in and isolated from
      the myocardium of neonatal and adult mice, rats, and humans; however, the precise
      origin and characterization of these cells remain unclear. Using a heterotopic
      mouse heart transplantation model, we investigated the origin and population
      dynamics of cardiac progenitor cells. Donor hearts from wild-type C57/BL6 female
      mice were transplanted into green fluorescent protein (GFP)-transgenic C57/BL6
      male mice. The donor hearts were collected 0, 2, 4, 8, and 12 weeks after
      transplantation. We used quantitative flow cytometry to analyze the number and
      origin of stem cells in the donor hearts and immunostaining to evaluate the time
      related changes in their characteristics. Extracardiac GFP-positive stem cells
      immigrated into the donor hearts soon after transplantation. Immunostaining
      revealed that these GFP-positive stem cells in the donor hearts gradually lost
      expression of the hematopoietic markers of CD45 and CD34 and shifted to express
      the cardiac-specific transcription factors GATA-4 and NKx2.5. A few of the GFP
      positive cells in the donor hearts finally acquired the mature cardiac phenotype
      in the absence of cell fusion with donor cardiomyocytes. Our discovery provides
      the first evidence that extracardiac stem cells may be of bone marrow origin,
      from which they can transform into cardiac progenitor cells in response to
      myocardial environment cues.

PMID- 17218399
TI  - Mesenchymal stem cells regulate angiogenesis according to their mechanical
      environment.
AB  - In fracture and bone defect healing, MSCs largely drive tissue regeneration. MSCs
      have been shown to promote angiogenesis both in vivo and in vitro. Angiogenesis
      is a prerequisite to large tissue reconstitution. The present study investigated
      how mechanical loading of MSCs influences their proangiogenic capacity. The
      results show a significant enhancement of angiogenesis by conditioned media from
      mechanically stimulated compared with unstimulated MSCs in two-dimensional tube
      formation and three-dimensional spheroid sprouting assays. In particular,
      proliferation but not migration or adhesion of endothelial cells was elevated.
      Promotion of angiogenesis was dependent upon fibroblast growth factor receptor 1
      (FGFR1) signaling. Moreover, stimulation of tube formation was inhibited by
      vascular endothelial growth factor receptor (VEGFR) tyrosine kinase blocking.
      Screening for the expression levels of different soluble regulators of
      angiogenesis revealed an enrichment of matrix metalloprotease 2, transforming
      growth factor beta1, and basic fibroblast growth factor but not of vascular
      endothelial growth factor in response to mechanical stimulation. In conclusion,
      mechanical loading of MSCs seems to result in a paracrine stimulation of
      angiogenesis, most likely by the regulation of a network of several angiogenic
      molecules. The underlying mechanism appears to be dependent on the FGFR and VEGFR
      signaling cascades and might be mediated by an additional cross-talk with other
      pathways.

PMID- 17218400
TI  - Brain transplantation of immortalized human neural stem cells promotes functional
      recovery in mouse intracerebral hemorrhage stroke model.
AB  - We have generated stable, immortalized cell lines of human NSCs from primary
      human fetal telencephalon cultures via a retroviral vector encoding v-myc.
      HB1.F3, one of the human NSC lines, expresses a normal human karyotype of 46, XX,
      and nestin, a cell type-specific marker for NSCs. F3 has the ability to
      proliferate continuously and differentiate into cells of neuronal and glial
      lineage. The HB1.F3 human NSC line was used for cell therapy in a mouse model of
      intracerebral hemorrhage (ICH) stroke. Experimental ICH was induced in adult mice
      by intrastriatal administration of bacterial collagenase; 1 week after surgery,
      the rats were randomly divided into two groups so as to receive intracerebrally
      either human NSCs labeled with beta-galactosidase (n = 31) or phosphate-buffered
      saline (PBS) (n = 30). Transplanted NSCs were detected by 5-bromo-4-chloro-3
      indolyl-beta-d-galactoside histochemistry or double labeling with beta
      galactosidase (beta-gal) and mitogen-activated protein (MAP)2, neurofilaments
      (both for neurons), or glial fibrillary acidic protein (GFAP) (for astrocytes).
      Behavior of the animals was evaluated for period up to 8 weeks using modified
      Rotarod tests and a limb placing test. Transplanted human NSCs were identified in
      the perihematomal areas and differentiated into neurons (beta-gal/MAP2(+) and
      beta-gal/NF(+)) or astrocytes (beta-gal/GFAP(+)). The NSC-transplanted group
      showed markedly improved functional performance on the Rotarod test and limb
      placing after 2-8 weeks compared with the control PBS group (p < .001). These
      results indicate that the stable immortalized human NSCs are a valuable source of
      cells for cell replacement and gene transfer for the treatment of ICH and other
      human neurological disorders. Disclosure of potential conflicts of interest is
      found at the end of this article.

PMID- 17218401
TI  - A population of myogenic stem cells that survives skeletal muscle aging.
AB  - Age-related decline in integrity and function of differentiated adult tissues is
      widely attributed to reduction in number or regenerative potential of resident
      stem cells. The satellite cell, resident beneath the basal lamina of skeletal
      muscle myofibers, is the principal myogenic stem cell. Here we have explored the
      capacity of satellite cells within aged mouse muscle to regenerate skeletal
      muscle and to self-renew using isolated myofibers in tissue culture and in vivo.
      Satellite cells expressing Pax7 were depleted from aged muscles, and when aged
      myofibers were placed in culture, satellite cell myogenic progression resulted in
      apoptosis and fewer total differentiated progeny. However, a minority of cultured
      aged satellite cells generated large clusters of progeny containing both
      differentiated cells and new cells of a quiescent satellite-cell-like phenotype
      characteristic of self-renewal. Parallel in vivo engraftment assays showed that,
      despite the reduction in Pax7(+) cells, the satellite cell population associated
      with individual aged myofibers could regenerate muscle and self-renew as
      effectively as the larger population of satellite cells associated with young
      myofibers. We conclude that a minority of satellite cells is responsible for
      adult muscle regeneration, and that these stem cells survive the effects of aging
      to retain their intrinsic potential throughout life. Thus, the effectiveness of
      stem-cell-mediated muscle regeneration is determined by both extrinsic
      environmental influences and diversity in intrinsic potential of the stem cells
      themselves.

PMID- 17218402
TI  - Effects of culture conditions and bone morphogenetic protein 2 on extent of
      chondrogenesis from human embryonic stem cells.
AB  - The study of human embryonic stem cells (hESCs) can provide invaluable insights
      into the development of numerous human cell and tissue types in vitro. In this
      study, we addressed the potential of hESCs to undergo chondrogenesis and
      demonstrated the potential of hESC-derived embryoid bodies (EBs) to undergo a
      well-defined full-span chondrogenesis from chondrogenic induction to hypertrophic
      maturation. We compared chondrogenic differentiation of hESCs through EB direct
      plating outgrowth system and EB-derived high-density micromass systems under
      defined serumfree chondrogenic conditions and demonstrated that cell-to-cell
      contact and bone morphogenetic protein 2 (BMP2) treatment enhanced chondrocyte
      differentiation, resulting in the formation of cartilaginous matrix rich in
      collagens and proteoglycans. Provision of a high-density three-dimensional (3D)
      microenvironment at the beginning of differentiation is critical in driving
      chondrogenesis because increasing EB seeding numbers in the EB-outgrowth system
      was unable to enhance chondrogenesis. Temporal order of chondrogenic
      differentiation and hypertrophic maturation indicated by the gene expression
      profiles of Col 1, Col 2, and Col 10, and the deposition of extracellular matrix
      (ECM) proteins, proteoglycans, and collagen II and X demonstrated that the in
      vivo progression of chondrocyte maturation is recapitulated in the hESC-derived
      EB model system established in this study. Furthermore, we also showed that BMP2
      can influence EB differentiation to multiple cell fates, including that of
      extraembryonic endodermal and mesenchymal lineages in the EB-outgrowth system,
      but was more committed to driving the chondrogenic cell fate in the EB micromass
      system. Overall, our findings provide a potential 3D model system using hESCs to
      delineate gene function in lineage commitment and restriction of chondrogenesis
      during embryonic cartilage development.

PMID- 17218404
TI  - Bone morphogenetic protein-mediated modulation of lineage diversification during
      neural differentiation of embryonic stem cells.
AB  - Embryonic stem cells (ES cells) can give rise to a broad spectrum of neural cell
      types. The biomedical application of ES cells will require detailed knowledge on
      the role of individual factors modulating fate specification during in vitro
      differentiation. Bone morphogenetic proteins (BMPs) are known to exert a
      multitude of diverse differentiation effects during embryonic development. Here,
      we show that exposure to BMP2 at distinct stages of neural ES cell
      differentiation can be used to promote specific cell lineages. During early ES
      cell differentiation, BMP2-mediated inhibition of neuroectodermal differentiation
      is associated with an increase in mesoderm and smooth muscle differentiation. In
      fibroblast growth factor 2-expanded ES cell-derived neural precursors, BMP2
      supports the generation of neural crest phenotypes, and, within the neuronal
      lineage, promotes distinct subtypes of peripheral neurons, including cholinergic
      and autonomic phenotypes. BMP2 also exerts a density-dependent promotion of
      astrocyte differentiation at the expense of oligodendrocyte formation.
      Experiments involving inhibition of the serine threonine kinase FRAP support the
      notion that these effects are mediated via the JAK/STAT pathway. The preservation
      of diverse developmental BMP2 effects in differentiating ES cell cultures
      provides interesting prospects for the enrichment of distinct neural phenotypes
      in vitro.

PMID- 17218403
TI  - Two distinct stem cell lineages in murine bone marrow.
AB  - Mesenchymal stem cells (MSC), a distinct type of adult stem cell, are easy to
      isolate, culture, and manipulate in ex vivo culture. These cells have great
      plasticity and potential for therapeutic application, but their properties are
      poorly understood because of their low frequency and the lack of knowledge on
      cell surface markers and their location of origin. The present study was designed
      to address the undefined lineage relationship of hematopoietic and mesenchymal
      stem cells. Genetically marked, highly purified hematopoietic stem cells (HSCs)
      were transplanted into wild-type animals and, after bone marrow repopulation, the
      progeny were rigorously investigated for differentiation potential into
      mesenchymal tissues by analyzing in vitro differentiation into mesenchymal
      tissues. None/very little of the hematopoietic cells contributed to colony
      forming units fibroblast activity and mesenchymal cell differentiation; however,
      unfractionated bone marrow cells resulted in extensive replacement of not only
      hematopoietic cells but also mesenchymal cells, including MSCs. As a result, we
      concluded that purified HSCs have no significant potency to differentiate into
      mesenchymal lineage. The data strongly suggest that hematopoietic cells and
      mesenchymal lineage cells are derived from individual lineage-specific stem
      cells. In addition, we succeeded in visualizing mesenchymal lineage cells using
      in vivo microimaging and immunohistochemistry. Flow cytometric analysis revealed
      CD140b (PDGFRbeta) could be a specific marker for mesenchymal lineage cells. The
      results may reinforce the urgent need for a more comprehensive view of the
      mesenchymal stem cell identity and characteristics. Disclosure of potential
      conflicts of interest is found at the end of this article.

PMID- 17218405
TI  - A cassette system to study embryonic stem cell differentiation by inducible RNA
      interference.
AB  - Although differentiation of pluripotent embryonic stem cells is restricted by a
      hierarchy of transcription factors, little is known about whether post
      transcriptional mechanisms similarly regulate early embryoid differentiation. We
      developed a system where small hairpin (sh)RNAs can be induced in embryonic stem
      (ES) cells from a defined locus following integration by Flp recombinase-mediated
      DNA recombination. To verify the system, the key transcription factor Stat3,
      which maintains pluripotency, was downregulated by shRNA, and the expected
      morphological and biochemical markers of differentiation were observed. Induction
      of shRNA specific for the post-transcriptional regulator Brf1 (Zfp36L1) amplified
      the cardiac markers with strong stimulation of cardiomyocyte formation within
      embryoid bodies. These findings identify Brf1 as a novel potential regulator of
      cardiomyocyte formation and suggest that post-transcriptional mechanisms are of
      importance to early development and, possibly, to regenerative medicine. The
      inducible RNA interference system presented here should also allow assignment of
      function for candidate genes with suspected roles in ES cell development.
      Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 17218407
TI  - The effect of mechanical stretch on cyclooxygenase type 2 expression and
      activator protein-1 and nuclear factor-kappaB activity in human amnion cells.
AB  - Stretch of the uterus plays a role in parturition. Uterine stretch also leads to
      stretch of the fetal membranes, including the amnion, an important source of
      prostaglandin E2 (PGE2). We tested the hypothesis that stretch of the amnion
      leads to increased cyclooxygenase (COX)-2 expression and PGE2 synthesis and
      investigated the mechanisms involved. We obtained amnion from women undergoing
      term elective cesarean section and isolated amnion epithelial cells. These cells
      were subjected to 11% static stretch. Stretch increased COX-2 expression and PGE2
      production. EMSA studies showed that stretch increased both activator protein-1
      (AP-1) and nuclear factor-kappaB (NF-kappaB) DNA binding at 1 and 6 h. In
      contrast, IL-1beta increased both AP-1 and NF-kappaB DNA binding at 1 h only.
      Chromatin immunoprecipitation studies confirmed that stretch increased binding of
      NF-kappaB to the COX-2 promoter in vivo. Stretch had no effect on inhibitory
      kappaBalpha (IkappaBalpha) levels at the early time points but caused a decrease
      at 4 h. IL-1beta stimulation decreased IkappaBalpha levels after 30 min. MG132, a
      proteasome inhibitor, inhibited only the second stretch-induced increase in NF
      kappaB binding. This suggests that stretch initially activates NF-kappaB via a
      nonclassical pathway, which does not involve the inhibitory-kappa kinase-induced
      degradation of IkappaBalpha. The second peak of NF-kappaB activation may be
      mediated by the classical mechanism. Stretch of the amnion may contribute to
      increased expression of COX-2- and other AP-1- and NF-kappaB-regulated genes with
      the onset of labor in the human.

PMID- 17218406
TI  - Luteinizing hormone-induced caspase activation in rat preovulatory follicles is
      coupled to mitochondrial steroidogenesis.
AB  - Atresia and luteolysis are well-documented processes in which most of the growing
      ovarian follicles and all corpora lutea, respectively, are eliminated by
      apoptosis. We have previously reported that LH and FSH enhance caspase-3 and -7
      activity and apoptosis in the theca-interstitial cells of rat preovulatory
      follicles in culture. Here we have used cultured follicles to examine whether LH
      induced caspase activation is related to the ability of LH to stimulate steroid
      production. In these studies, we used three inhibitors of enzymes involved in
      steroid production: aminoglutethimide and ketoconazole, acting on cytochrome P450
      side-chain cleavage (P450scc) located at the mitochondria, and epostane, acting
      on 3beta-hydroxysteroid dehydrogenase located at the endoplasmic reticulum. We
      found that treatment with either aminoglutethimide or ketoconazole, but not with
      epostane, significantly reduced LH-induced caspase-3 and -7 activation and
      apoptosis, suggesting the mediation of LH-induced caspase activation by P450scc.
      Supplementing pregnenolone, the product of P450scc catalysis, to follicles
      treated with aminoglutethimide did not restore LH-induced caspase activation. On
      the other hand, treatment with antioxidants inhibited LH-induced caspase
      activation. Moreover, LH treatment was associated with an increase in reactive
      oxygen species which was inhibited by aminoglutethimide. Thus, P450scc catalysis
      results in an increase in reactive oxygen species, which in turn may
      trigger/facilitate caspase-3 activation. Finally, we found that in rat corpora
      lutea in vivo, an increase in steroidogenesis was accompanied by an increase in
      caspase activity. Thus, this study reveals a linkage between two seemingly
      distinct processes in which LH-induced caspase activation in cultured rat
      preovulatory follicles is coupled to mitochondrial steroidogenesis via P450scc.

PMID- 17218408
TI  - 3'5'-cyclic adenosine monophosphate-dependent up-regulation of phosphodiesterase
      type 3A in porcine cumulus cells.
AB  - The means by which cumulus cells react to gonadotropin stimulation and regulate
      the subsequent production and degradation of cAMP are largely unknown. In this
      article, we report that cyclic nucleotide phosphodiesterase (PDE) type 3A (Pde3a)
      is transcriptionally regulated in porcine cumulus cells by a cAMP-dependent
      pathway during in vitro maturation (IVM). cAMP-PDE activity was increased in the
      cumulus-oocyte complex (COC) after 10 h of IVM, and 78% of this increase was
      sensitive to a Pde3-specific inhibitor, cilostamide. Although no variation was
      observed in the oocyte, cilostamide-sensitive cAMP-PDE activity increased in the
      cumulus cells after IVM. This was supported by Western blotting, which showed
      that the intensity of a 135-kDa anti-Pde3a immunoreactive band was increased in
      COC after IVM. The Pde3a mRNA level was up-regulated 28-fold in the COC after 4 h
      of IVM and remained high up to 12 h. The mRNA up-regulation and increased
      activity were inhibited by an RNA synthesis inhibitor, alpha-amanitin. The
      cilostamide-sensitive increase in PDE activity was inhibited by a protein
      synthesis inhibitor, cycloheximide. Pregnant mare serum gonadotropin (PMSG)
      caused dose-dependent activation of Pde3. The PMSG-dependent increase in Pde3
      activity and Pde3a mRNA were mimicked by the adenylyl cyclase activator forskolin
      or prostaglandin E2. PMSG-dependent Pde3 activation was inhibited by the protein
      kinase A-specific inhibitor H89. Collectively, our results show for the first
      time that degradation of the intracellular cyclic nucleotide by Pde3a is
      transcriptionally up-regulated via a cAMP-dependent pathway in cumulus cells,
      suggesting that it has a functional role during the ovulatory gonadotropin surge.

PMID- 17218410
TI  - Activating protein-1 cooperates with steroidogenic factor-1 to regulate 3',5'
      cyclic adenosine 5'-monophosphate-dependent human CYP11A1 transcription in vitro
      and in vivo.
AB  - The CYP11A1 encodes cytochrome P450scc, catalyzing the first step of
      steroidogenesis in adrenals and gonads under the control of cAMP-mediated
      hormonal signals. The cAMP-induced activation of human CYP11A1 has been suggested
      to depend on the transcription factor cAMP-responsive element-binding protein
      (CREB), but the CREB action cannot explain the chronic cAMP effect on CYP11A1
      activation. To further understand the mechanism of human CYP11A1 activation, we
      dissected the functions of the upstream cAMP responsive sequences (U-CRS)
      containing a core sequence, U identical to the steroidogenic factor-1 (SF-1)
      binding site, and two flanking TPA-responsive element/cAMP-responsive element
      like elements, C1 and C2. The EMSA assays showed that the binding activities of U
      with SF-1 as well as C1 or C2 with activating protein-1 (AP-1)/CREB-like proteins
      are induced by cAMP. The results from the site-directed mutagenesis analyses
      revealed that all three elements are required for the U-CRS function and any
      mutation of C1, C2, or U impairs the response to cAMP stimulation. In transgenic
      mice, the single or double mutations of C1 and C2 resulted in the reduction of
      reporter gene expression accompanied with poor hormonal response. The cAMP
      induction on the U-CRS activity was mimicked and enhanced by the overexpressed c
      Jun in the presence of SF-1, but was abolished by the overexpression of an AP-1
      dominant-negative mutant, FosB2. Furthermore, we have observed the interdependent
      transactivation between SF-1 and c-Jun on the U-CRS function. These results
      collectively demonstrate that SF-1 and AP-1 cooperate to activate CYP11A1
      transcription in vitro and in vivo.

PMID- 17218409
TI  - Androgen regulation of prostate morphoregulatory gene expression: Fgf10-dependent
      and -independent pathways.
AB  - Androgens are essential and sufficient for prostate gland morphogenesis; however,
      the downstream gene targets that mediate this action are unclear. To identify
      androgen-regulated genes involved in prostate development, we used short-term
      organ culture and examined the effect of testosterone on the expression of
      several critical prostate morphoregulatory genes. Rat ventral prostates (VP) and
      lateral prostates (LP) were collected at birth, and contralateral lobes were
      cultured for 18 h in the presence or absence of 10 nM testosterone with or
      without OH-flutamide to block residual androgens. Gene expression was quantitated
      using real-time RT-PCR. Although expression of Fgf10, Nkx3.1, and Ptc was
      increased in both prostate lobes, other genes were regulated by testosterone in a
      lobe-specific manner. This included up-regulation of epithelial genes FgfR2iiib,
      Shh, Hoxb13, and Bmp7 in the VP specifically and down-regulation of mesenchymal
      genes Wnt5a (VP) and Bmp4 (LP). Thus, in addition to stimulation of homeobox
      genes and paracrine-acting growth factors, androgens may positively regulate
      prostatic development through suppression of growth inhibitory genes. Because
      previous studies revealed a similar gene regulation pattern in response to
      exogenous Fgf10, experiments were performed to identify androgen-regulated genes
      mediated through Fgf10 signaling. Short-term VP and LP cultures with FgfR
      antagonist PD173074 and Mek inhibitor U0126 identified epithelial Shh and Hoxb13
      up-regulation by androgens to be Fgf10-dependent. We propose that androgen
      regulation of prostate development is mediated through positive and negative
      regulation of multiple morphoregulatory genes acting in combination through
      complex gene networks. Lobe-specific responses may provide a developmental basis
      for prostate gland heterogeneity.

PMID- 17218411
TI  - Development of l-CDB-4022 as a nonsteroidal male oral contraceptive: induction
      and recovery from severe oligospermia in the adult male cynomolgus monkey (Macaca
      fascicularis).
AB  - The present study was undertaken to examine the antispermatogenic effect of l-CDB
      4022 in the adult male cynomolgus monkey. Monkeys (four per group) were dosed via
      nasogastric tube for 7 d with l-CDB-4022 at 12.5 mg/kg.d or vehicle (d 0=first
      day of dosing). Plasma levels of l-CDB-4022 and its deesterified metabolite were
      nondetectable prior to treatment and in all vehicle-treated monkeys. Peak levels
      of l-CDB-4022 and its metabolite were observed at 4 h after dosing with steady
      state levels apparent around d 4. Sperm concentration and total sperm per
      ejaculate were decreased to levels below 1x10(6) sperm/ml or sperm/ejaculate in l
      CDB-4022-treated monkeys by d 17 and remained suppressed through wk 6. Sperm
      motility also declined to 0% for 6 wk. Testicular volume was reduced in l-CDB
      4022-treated monkeys through d 21. The left testis and epididymis were removed
      from all monkeys on d 24. At this time, the most mature germ cells in the
      seminiferous tubules of testes from l-CDB-4022-treated monkeys were either
      spermatocytes or round spermatids. Immature germ cells, but not mature sperm,
      were found in the efferent ducts and collapsed epididymal lumen of l-CDB-4022
      treated monkeys. A steady recovery in sperm motility, concentration, and total
      sperm per ejaculate was observed in l-CDB-4022-treated monkeys such that these
      parameters were not different from those of vehicle-treated monkeys by wk 16.
      Volume of the remaining testis increased in vehicle- and l-CDB-4022-treated
      monkeys after hemicastration; however, the increase in l-CDB-4022-treated monkeys
      was delayed compared with that observed in the vehicle-treated monkeys. The
      morphology of the remaining testis and epididymis, which were removed on wk 17,
      was normal. Serum inhibin B levels were increased in l-CDB-4022-treated monkeys
      during the dosing interval; thereafter serum inhibin B levels declined such that
      there was no difference between the groups by wk 3. l-CDB-4022 treatment did not
      affect circulating levels of testosterone, LH, FSH, or estradiol. In conclusion,
      these data indicate that in the cynomolgus monkey, a representative higher
      primate, l-CDB-4022 exerts a selective antispermatogenic action, which was
      reversible under the conditions of this study and thus has potential as a
      nonhormonal oral male contraceptive.

PMID- 17218412
TI  - Glucokinase regulates reproductive function, glucocorticoid secretion, food
      intake, and hypothalamic gene expression.
AB  - Because appetite, hypothalamic gene expression, reproductive function, and
      adrenal function are highly sensitive to acute changes in plasma glucose levels,
      it has been hypothesized hypothalamic neurons sensitive to glucose play a role in
      regulating these functions. To assess this hypothesis, we examined these
      neuronendocrine functions in mice in which the glucokinase gene, which plays an
      essential role in neuroendocrine glucose sensing, has been ablated.
      Haploinsufficiency in heterozygous glucokinase knockout mice produced effects
      similar to those produced by hypoglycemia: impaired reproductive function,
      elevated plasma corticosterone, increased food intake, and hypothalamic gene
      expression similar to that observed in fasted or leptin-deficient obese mice
      (increased hypothalamic neuropeptide Y mRNA and reduced hypothalamic
      proopiomelanocortin mRNA). Plasma glucose was elevated 2-fold in glucokinase
      knockout mice, consistent with a maturity-onset diabetes of the young phenotype,
      but plasma insulin and leptin levels were normal. These data support the
      hypothesis that glucokinase plays a key role in the neuroendocrine regulation of
      metabolic economy.

PMID- 17218413
TI  - Effects of prenatal dexamethasone treatment on postnatal physical, endocrine, and
      social development in the common marmoset monkey.
AB  - The prophylactic treatment of diagnosed preterm delivery with synthetic
      glucocorticoids, such as dexamethasone (DEX), is commonplace. Long-term effects
      of such treatment are not well understood. In the present study, we exposed
      pregnant common marmosets (Callithrix jacchus), small-bodied monkeys that are
      therefore advantageous for long-term primate studies, to daily repeated DEX (5
      mg/kg orally) either during early (d 42-48) or late (d 90-96) pregnancy
      (gestation period of 144 d). Relative to control, we investigated DEX effects in
      terms of maternal endocrinology (plasma cortisol and estrogen titers) and
      offspring physical growth, plasma and urinary ACTH and cortisol titers, and
      social and maintenance behaviors from birth to weaning. Both DEX treatments
      resulted in markedly reduced maternal plasma cortisol titers during treatment and
      reduced estimated gestation period. Both treatments were without effects on
      neonate morphometric measurements and basal hypothalamic-pituitary-adrenal axis
      activity. Early DEX treatment resulted in increased infant body weight at
      postnatal d 56 and 84, co-occurring at the behavioral level with increased time
      spent in eating solid food, a mobile state, solitary play, and exhibiting tail
      hair piloerection. The constellation of physical and behavioral effects of early
      DEX suggests interesting parallels with the human metabolic syndrome, providing
      primate support that the latter is causally associated with the fetal
      environment, including prenatal programming. This novel primate in vivo evidence
      for postnatal effects of prenatal synthetic glucocorticoid exposure indicates the
      importance of improved understanding of this acute clinical treatment in terms of
      its long-term effects on offspring well-being.

PMID- 17218414
TI  - The rat thyroid hormone receptor (TR) Deltabeta3 displays cell-, TR isoform-, and
      thyroid hormone response element-specific actions.
AB  - The THRB gene encodes the well-described thyroid hormone (T3) receptor (TR)
      isoforms TRbeta1 and TRbeta2 and two additional variants, TRbeta3 and
      TRDeltabeta3, of unknown physiological significance. TRbeta1, TRbeta2, and
      TRbeta3 are bona fide T3 receptors that bind DNA and T3 and regulate expression
      of T3-responsive target genes. TRDeltabeta3 retains T3 binding activity but lacks
      a DNA binding domain and does not activate target gene transcription.
      TRDeltabeta3 can be translated from a specific TRDeltabeta3 mRNA or is
      coexpressed with TRbeta3 from a single transcript that contains an internal
      TRDeltabeta3 translation start site. In these studies, we provide evidence that
      the TRbeta3/Deltabeta3 locus is present in rat but not in other vertebrates,
      including humans. We compared the activity of TRbeta3 with other TR isoforms and
      investigated mechanisms of action of TRDeltabeta3 at specific thyroid hormone
      response elements (TREs) in two cell types. TRbeta3 was the most potent isoform,
      but TR potency was TRE dependent. TRDeltabeta3 acted as a cell-specific and TRE
      dependent modulator of TRbeta3 when coexpressed at low concentrations. At higher
      concentrations, TRDeltabeta3 was a TRE-selective and cell-specific antagonist of
      TRalpha1, -beta1, and -beta3. Both TRbeta3 and TRDeltabeta3 were expressed in the
      nucleus in the absence and presence of hormone, and their actions were determined
      by cell type and TRE structure, whereas TRDeltabeta3 actions were also dependent
      on the TR isoform with which it interacted. Analysis of these complex responses
      implicates a range of nuclear corepressors and coactivators as cell-, TR isoform
      , and TRE-specific modulators of T3 action.

PMID- 17218415
TI  - Angiotensin II receptor type 1-mediated vascular oxidative stress and
      proinflammatory gene expression in aldosterone-induced hypertension: the possible
      role of local renin-angiotensin system.
AB  - Recently, aldosterone has been shown to activate local renin-angiotensin system
      in vitro. To elucidate the potential role of local renin-angiotensin system in
      aldosterone-induced cardiovascular injury, we investigated the effects of
      selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL),
      angiotensin (Ang) II type 1 receptor antagonist candesartan (ARB), and superoxide
      dismutase mimetic tempol (TEM) on the development of hypertension, vascular
      injury, oxidative stress, and inflammatory-related gene expression in aldosterone
      treated hypertensive rats. The increased systolic blood pressure and vascular
      inflammatory changes were attenuated by cotreatment either with EPL, ARB, or TEM.
      Aldosterone increased angiotensin-converting enzyme expression in the aortic
      tissue; its effects were blocked by EPL but not by ARB or TEM. Aldosterone also
      increased Ang II contents in the aortic tissue in the presence of low circulating
      Ang II concentrations. Aldosterone induced expression of various inflammatory
      related genes, whose effects were abolished by EPL, whereas the inhibitory
      effects of ARB and TEM varied depending on the gene. Aldosterone caused greater
      accumulation of the oxidant stress marker 4-hydroxy-2-neonenal in the
      endothelium; its effect was abolished by EPL, ARB, or TEM. Aldosterone increased
      mRNA levels of reduced nicotinamide adenine dinucleotide phosphate oxidase
      components; their effect was abolished by EPL, whereas ARB and TEM decreased only
      the p47phox mRNA level but not that of p22phox or gp91phox. The present findings
      suggest that the Ang II-dependent pathway resulting from vascular angiotensin
      converting enzyme up-regulation and Ang II-independent pathway are both involved
      in the underlying mechanisms resulting in the development of hypertension,
      vascular inflammation, and oxidative stress induced by aldosterone.

PMID- 17218416
TI  - Neuroendocrine plasticity in the anterior pituitary: gonadotropin-releasing
      hormone-mediated movement in vitro and in vivo.
AB  - The secretion of LH is cued by the hypothalamic neuropeptide, GnRH. After
      delivery to the anterior pituitary gland via the hypothalamic-pituitary portal
      vasculature, GnRH binds to specific high-affinity receptors on the surface of
      gonadotrope cells and stimulates synthesis and secretion of the gonadotropins,
      FSH, and LH. In the current study, GnRH caused acute and dramatic changes in
      cellular morphology in the gonadotrope-derived alphaT3-1 cell line, which
      appeared to be mediated by engagement of the actin cytoskeleton; disruption of
      actin with jasplakinolide abrogated cell movement and GnRH-induced activation of
      ERK. In live murine pituitary slices infected with an adenovirus-containing Rous
      sarcoma virus-green fluorescent protein, selected cells responded to GnRH by
      altering their cellular movements characterized by both formation and extension
      of cell processes and, surprisingly, spatial repositioning. Consistent with the
      latter observation, GnRH stimulation increased the migration of dissociated
      pituitary cells in transwell chambers. Our data using live pituitary slices are a
      striking example of neuropeptide-evoked movements of cells outside the central
      nervous system and in a mature peripheral endocrine organ. These findings call
      for a fundamental change in the current dogma of simple passive diffusion of LH
      from gonadotropes to capillaries in the pituitary gland.

PMID- 17218417
TI  - Alteration of cerebellar neurotropin messenger ribonucleic acids and the lack of
      thyroid hormone receptor augmentation by staggerer-type retinoic acid receptor
      related orphan receptor-alpha mutation.
AB  - The mutant mouse staggerer (sg) harbors a deletion within the gene encoding the
      retinoic acid receptor-related orphan receptor-alpha (RORalpha). Homozygotes show
      aberrant cerebellar development. However, the mechanisms responsible for the
      cerebellar defect are still poorly understood. In the present study, the
      involvement of neurotropins (NTs), including nerve growth factor, brain-derived
      neurotropic factor, NT-3 and NT-4/5, and their receptors, which play a crucial
      role in brain development, on the cerebellar defects of sg mice was studied by
      semiquantitative RT-PCR and in situ hybridization histochemistry. An evident
      alteration of these mRNA levels was observed in both heterozygotes and
      homozygotes. Such difference was most evident in the internal granule cell layer.
      Because the changes in NT expression as well as morphological alterations in sg
      cerebellum are similar to those in hypothyroid animals, the effect of mutant
      RORalpha (RORsg) on transcriptional regulation through the thyroid hormone (TH)
      response element or the ROR response element (RORE) was then studied. RORsg
      neither activated the transcription through RORE nor suppressed RORalpha-induced
      transcription, indicating that it does not function as a dominant negative
      inhibitor. On the other hand, although wild-type RORalpha augmented TH receptor
      (TR)alpha1/beta1-mediated transcription through various TH response elements,
      RORsg was not effective in augmenting TR action. These results suggest that the
      cerebellar defect of the sg mouse is partly caused by the altered expression of
      NTs and the lack of augmentation of TR-mediated transcription by RORalpha as well
      as the absence of RORalpha action through RORE.

PMID- 17218418
TI  - Adrenomedullin-2, a novel calcitonin/calcitonin-gene-related peptide family
      peptide, relaxes rat mesenteric artery: influence of pregnancy.
AB  - Adrenomedullin-2 (ADM2), a novel calcitonin/calcitonin-gene-related peptide
      family peptide, is reported to reduce blood pressure in both normal and
      hypertensive rats. This study demonstrates gestational regulation of circulatory
      ADM2 in rat plasma. ADM2 dose-dependently reduces the mean arterial pressure in
      rats, whereas the hypotensive effect of ADM2 is significantly higher during
      pregnancy. In addition, immunoreactive ADM2 protein is distributed in
      perivascular fibers of rat mesenteric artery, and levels of pre-pro-ADM2 are
      significantly (P<0.05) elevated in pregnant compared with nonpregnant rat
      mesenteric artery. Furthermore, incubation of endothelium intact arterial tissue
      from pregnant rats with ADM217-47, an ADM2 antagonist, shifted the dose-dependent
      relaxation curve to the right in wire myography. Inhibition of soluble guanylate
      cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 microM) or
      endothelial nitric oxide synthase with N-nitro-L-arginine methyl ester (100
      microM) reduced the relaxation of mesenteric artery induced by ADM2. Inhibition
      of adenylate cyclase with SQ22536 (10 microM) or protein kinase A with the Rp
      diastereomer of cyclic adenosine 3',5'-phosphorothioate (10 microM) also reduced
      the maximal relaxation responses induced by ADM2. Blockade of calcium-activated
      potassium channels with tetraethylammonium chloride (1 mM) inhibited the ADM2
      induced relaxation, whereas blockade of ATP-sensitive potassium channels with
      glybenclamide (10 microM) did not affect the relaxation response. Hence the
      mechanism of ADM2-induced vasorelaxation is nitric oxide and receptor mediated
      and cGMP and cAMP dependent and occurs through activation of calcium-activated
      potassium channels. In conclusion, rat pregnancy is associated with increased
      levels of circulatory and vascular tissue ADM2 with concomitant increase in the
      in vivo hypotensive effect of ADM2 and vascular reactivity of mesenteric artery
      to ADM2, thus suggesting involvement of ADM2 in vascular adaptations during
      pregnancy.

PMID- 17218419
TI  - A direct effect of aldosterone on endothelin-1 gene expression in vivo.
AB  - Aldosterone regulates sodium reabsorption in epithelial tissues such as the
      kidney and colon, via a pathway involving the activation of intracellular
      mineralocorticoid receptors (MR), induction of specific target genes, and a
      subsequent increase in sodium channel activity. Characterized aldosterone target
      genes in epithelia include the serum and glucocorticoid-regulated kinase 1 and
      the corticosteroid hormone-induced factor. Endothelin-1 (ET-1) is a potent
      vasoconstrictor that alters both sodium transport and hydrogen ion secretion in
      the kidney. Recent studies in a mouse medullary collecting duct cell line and rat
      A-10 smooth muscle cells have demonstrated an acute response of ET-1 gene
      expression to aldosterone. In the present study, we have investigated the ET-1
      gene in vivo as a potential direct aldosterone-regulated target gene in the
      kidney and colon. Adrenalectomized rats given a single dose of aldosterone were
      found to have a 2-fold increase in ET-1 mRNA levels in the kidney and colon after
      1 h. No significant changes in mRNA levels were detected for the related isoforms
      ET-2 or ET-3. Cotreatment with aldosterone and potassium canrenoate, a MR
      antagonist, blocked induction of ET-1 mRNA, suggesting that induction was
      mediated via the MR. In a time course study, ET-1 mRNA levels were induced
      rapidly by aldosterone, with levels of ET-1 mRNA maximally increased 2- and 2.5
      fold after 1 h in the kidney and colon, respectively. These results suggest that
      ET-1 is a direct aldosterone gene target in the kidney and colon and may play an
      important role in aldosterone-regulated ion homeostasis.

PMID- 17218420
TI  - Identification and characterization of multiple corticotropin-releasing factor
      type 2 receptor isoforms in the rat esophagus.
AB  - The rat esophagus shares some cellular features with skin squamous epithelium and
      striated muscle that express high levels of corticotropin-releasing factor type 2
      (CRF2) receptors or their cognate ligand urocortin (Ucn) 1, 2, and 3. We
      investigated the expression and cell signaling of CRF2 receptors and ligands in
      the rat esophagus and lower esophageal sphincter (LES) by RT-PCR and quantitative
      PCR in normal and corticosterone-treated whole esophageal tissue, laser capture
      microdissected layers, and isolated esophageal cells. The expression of CRF2
      receptor protein and intracellular cAMP and ERK1/2 responses to CRF agonists and
      CRF2 antagonist were determined in cultured esophageal cells and HEK-293 cells
      transfected with CRF2b receptors. CRF2 was abundantly expressed in the mucosa and
      longitudinal muscle layers of the esophagus and LES, whereas CRF1 expression was
      scarce. CRF2b wild-type transcript was predominantly expressed in the esophagus,
      and in addition, several new CRF2 splice variants including six CRF2a isoforms
      were identified. Expression of Ucn 1, Ucn 2, and to a smaller extent Ucn 3, but
      not CRF mRNA, was detected in the esophagus and LES. Ucn 1 and Ucn 2 stimulated
      dose-dependent cAMP production and ERK1/2 phosphorylation in the esophageal
      cells, whereas CRF and CRF1 agonist, cortagine, had less potent effects. In
      addition, Ucn 2-stimulated cAMP and ERK responses were blocked by the CRF2
      antagonist, astressin2-B. These data established the presence of a prominent CRF2
      signaling system in the esophagus and LES-encompassing multiple CRF2 receptor
      variants and Ucn, suggesting a functional role in secretomotor activity and
      epithelial and muscle cell proliferation.

PMID- 17218421
TI  - Increased Notch 1 expression and attenuated stimulatory G protein coupling to
      adenylyl cyclase in osteonectin-null osteoblasts.
AB  - Osteonectin, or secreted protein acidic and rich in cysteine, is one of the most
      abundant noncollagen matrix components in bone. This matricellular protein
      regulates extracellular matrix assembly and maturation in addition to modulating
      cell behavior. Mice lacking osteonectin develop severe low-turnover osteopenia,
      and in vitro studies of osteonectin-null osteoblastic cells showed that
      osteonectin supports osteoblast formation, maturation, and survival. The present
      studies demonstrate that osteonectin-null osteoblastic cells have increased
      expression of Notch 1, a well-documented regulator of cell fate in multiple
      systems. Furthermore, osteonectin-null cells are more plastic and less committed
      to osteoblastic differentiation, able to pursue adipogenic differentiation given
      the appropriate signals. Notch 1 transcripts are down-regulated by inducers of
      cAMP in both wild-type and osteonectin-null osteoblasts, suggesting that the
      mutant osteoblasts may have a defect in generation of cAMP in response to
      stimuli. Indeed, many bone anabolic agents signal through increased cAMP. Wild
      type and osteonectin-null osteoblasts generated comparable amounts of cAMP in
      response to forskolin, a direct stimulator of adenylyl cyclase. However, the
      ability of osteonectin-null osteoblasts to generate cAMP in response to cholera
      toxin, a direct stimulator of Gs, was attenuated. These data imply that
      osteonectin-null osteoblasts have decreased coupling of Gs to adenylyl cyclase.
      Because osteonectin promotes G protein coupling to an effector, our studies
      support the concept that low-turnover osteopenia can result from reducing G
      protein coupled receptor activity.

PMID- 17218422
TI  - Variation in senescent-dependent lung changes in inbred mouse strains.
AB  - Previous studies from our laboratories showed lung development differences
      between inbred strains of mice. In the present study, the C57BL/6J (B6) and
      DBA/2J (D2) strains were examined for senescent-dependent differences with
      respect to the lung structure and function. Specifically, we hypothesize that
      senescent changes in lung vary between strains due to identifiable gene
      expression differences. Quasi-static pressure-volume curves and respiratory
      impedance measurements were performed on 2- and 20-mo-old B6 and D2 mice. Lung
      volume at 30 cm H(2)O (V(30)) pressure was significantly (P < 0.01) increased
      with age in both strains, but the increase was proportionally greater in D2 (68%)
      than in B6 (40%) mice. In addition, decreased elastic recoil pressure at 50% of
      V(30) and a reduction in airway resistance as a function of positive end
      expiratory pressure were observed in 20-mo-old D2 mice but not in B6 mice.
      Morphometric analysis of lung parenchyma showed significant decreases in elastic
      fiber content with age in both strains, but the collagen content was
      significantly (P < 0.01) increased with age in D2 but not B6 mice at 20 mo.
      Furthermore, using quantitative RT-PCR methods, gene expression differences
      between strains suggested that D2 mice significantly (P < 0.05) downregulated the
      expressions of elastin (Eln) and procollagen I, III, and VI (Col1a1, Col3a1, and
      Col6a3) in lung tissue at 20 mo of age. These age-dependent changes were
      accompanied by an increased gene expression in matrix metalloproteinase 9 (Mmp9)
      in D2 and an increase in tissue inhibitor of matrix metalloproteinase (Timp1 and
      Timp4) in B6 mice. In conclusion, the results from the present study demonstrate
      that lung mechanics of both strains show significant age-dependent changes.
      However, changes in D2 mice are accelerated relative to B6 mice. Moreover, gene
      expression differences appear to be involved in the strain-specific changes of
      lung mechanic properties.

PMID- 17218423
TI  - Estradiol replacement reverses ovariectomy-induced muscle contractile and myosin
      dysfunction in mature female mice.
AB  - Skeletal muscle contractility and myosin function decline following ovariectomy
      in mature female mice. In the present study we tested the hypothesis that
      estradiol replacement can reverse those declines. Four-month-old female C57BL/6
      mice (n = 69) were ovariectomized (OVX) or sham operated. Some mice were treated
      immediately with placebo or 17beta-estradiol (OVX + E(2)) while other mice were
      treated 30 days postsurgery. Thirty or sixty days postsurgery, soleus muscles
      were assessed in vitro for contractile function and susceptibility to eccentric
      contraction-induced injury. Myosin structural dynamics was analyzed in extensor
      digitorum longus (EDL) muscles by electron paramagnetic resonance spectroscopy.
      Maximal isometric tetanic force was affected by estradiol status (P < 0.001)
      being approximately 10% less in soleus muscles from OVX compared with sham
      operated mice [168 mN (SD 16.7) vs. 180 mN (SD 14.4)] and was restored in OVX +
      E(2) mice [187 mN (SD 17.6)]. The fraction of strong-binding myosin during
      contraction was also affected (P = 0.045) and was approximately 15% lower in EDL
      muscles from OVX compared with OVX + E(2) mice [0.263 (SD 0.034) vs. 0.311 (SD
      0.022)]. Plasma estradiol levels were correlated with maximal isometric tetanic
      force (r = 0.458; P < 0.001) and active stiffness (r = 0.329; P = 0.044),
      indicating that circulating estradiol influenced muscle and myosin function.
      Estradiol was not effective in protecting muscle against an acute eccentric
      contraction-induced injury (P >or= 0.401) but did restore ovariectomy-induced
      increases in muscle wet mass caused by fluid accumulation. Collectively,
      estradiol had a beneficial effect on female mouse skeletal muscle.

PMID- 17218424
TI  - Influence of preexercise muscle glycogen content on transcriptional activity of
      metabolic and myogenic genes in well-trained humans.
AB  - To determine whether preexercise muscle glycogen content influences the
      transcription of several early-response genes involved in the regulation of
      muscle growth, seven male strength-trained subjects performed one-legged cycling
      exercise to exhaustion to lower muscle glycogen levels (Low) in one leg compared
      with the leg with normal muscle glycogen (Norm) and then the following day
      completed a unilateral bout of resistance training (RT). Muscle biopsies from
      both legs were taken at rest, immediately after RT, and after 3 h of recovery.
      Resting glycogen content was higher in the control leg (Norm leg) than in the Low
      leg (435 +/- 87 vs. 193 +/- 29 mmol/kg dry wt; P < 0.01). RT decreased glycogen
      content in both legs (P < 0.05), but postexercise values remained significantly
      higher in the Norm than the Low leg (312 +/- 129 vs. 102 +/- 34 mmol/kg dry wt; P
      < 0.01). GLUT4 (3-fold; P < 0.01) and glycogenin mRNA abundance (2.5-fold; not
      significant) were elevated at rest in the Norm leg, but such differences were
      abolished after exercise. Preexercise mRNA abundance of atrogenes was also higher
      in the Norm compared with the Low leg [atrogin: approximately 14-fold, P < 0.01;
      RING (really interesting novel gene) finger: approximately 3-fold, P < 0.05] but
      decreased for atrogin in Norm following RT (P < 0.05). There were no differences
      in the mRNA abundance of myogenic regulatory factors and IGF-I in the Norm
      compared with the Low leg. Our results demonstrate that 1) low muscle glycogen
      content has variable effects on the basal transcription of select metabolic and
      myogenic genes at rest, and 2) any differences in basal transcription are
      completely abolished after a single bout of heavy resistance training. We
      conclude that commencing resistance exercise with low muscle glycogen does not
      enhance the activity of genes implicated in promoting hypertrophy.

PMID- 17218425
TI  - Free radical-mediated skeletal muscle dysfunction in inflammatory conditions.
AB  - Loss of functional capacity of skeletal muscle is a major cause of morbidity in
      patients with a number of acute and chronic clinical disorders, including sepsis,
      chronic obstructive pulmonary disease, heart failure, uremia, and cancer.
      Weakness in these patients can manifest as either severe limb muscle weakness
      (even to the point of virtual paralysis), respiratory muscle weakness requiring
      mechanical ventilatory support, and/or some combination of these phenomena. While
      factors such as nutritional deficiency and disuse may contribute to the
      development of muscle weakness in these conditions, systemic inflammation may be
      the major factor producing skeletal muscle dysfunction in these disorders.
      Importantly, studies conducted over the past 15 years indicate that free radical
      species (superoxide, hydroxyl radicals, nitric oxide, peroxynitrite, and the free
      radical-derived product hydrogen peroxide) play an key role in modulating
      inflammation and/or infection-induced alterations in skeletal muscle function.
      Substantial evidence exists indicating that several free radical species can
      directly alter contractile protein function, and evidence suggests that free
      radicals also have important effects on sarcoplasmic reticulum function, on
      mitochondrial function, and on sarcolemmal integrity. Free radicals also modulate
      activation of several proteolytic pathways, including proteosomally mediated
      protein degradation and, at least theoretically, may also influence pathways of
      protein synthesis. As a result, free radicals appear to play an important role in
      regulating a number of downstream processes that collectively act to impair
      muscle function and lead to reductions in muscle strength and mass in
      inflammatory conditions.

PMID- 17218426
TI  - Simulated microgravity effects on the rat carotid and femoral arteries: role of
      contractile protein expression and mechanical properties of the vessel wall.
AB  - The goal of this study was to determine the effects of microgravity on
      myofilament protein expression and both passive and active length-force
      relationships in carotid and femoral arteries. Microgravity was simulated by 20
      day hindlimb unweighting (HU) in Wistar male rats, and carotid and femoral artery
      segments were isolated from both HU and control (CTL) rats for Western blot and
      length-force analysis. Western blots revealed that HU significantly decreased
      myosin light chain-20 (MLC-20) protein levels in both carotid and femoral
      arteries and decreased myosin heavy chain (MHC) in femoral artery. alpha-Actin
      levels were not altered by HU treatment in either artery. Length-force analysis
      demonstrated that HU did not change either passive or active length-force
      relationships in the femoral artery. HU-treated arterial rings developed
      significantly less force to 100 mM K(+) than CTL, but optimal lengths were
      identical. In the carotid artery, length-active force curves were identical for
      both CTL and HU; however the length-passive force curve for HU-treated rings
      exhibited a steeper slope than CTL, suggesting decreased compliance of the artery
      wall. In conclusion, our data suggest that the HU-induced decreases in both MLC
      20 and MHC in femoral artery are responsible for the decreased contraction to 100
      mM K(+) in HU-treated femoral artery rings. In the carotid artery, the HU-induced
      decrease in vessel wall compliance may counter any decrease in contractility
      caused by the decreased MLC-20 levels.

PMID- 17218427
TI  - Residence at 3,800-m altitude for 5 mo in growing dogs enhances lung diffusing
      capacity for oxygen that persists at least 2.5 years.
AB  - Mammals native to high altitude (HA) exhibit larger lung volumes than their
      lowland counterparts. To test the hypothesis that adaptation induced by HA
      residence during somatic maturation improves pulmonary gas exchange in adulthood,
      male foxhounds born at sea level (SL) were raised at HA (3,800 m) from 2.5 to 7.5
      mo of age and then returned to SL prior to somatic maturity while their
      littermates were simultaneously raised at SL. Following return to SL, all animals
      were trained to run on a treadmill; gas exchange and hemodynamics were measured
      2.5 years later at rest and during exercise while breathing 21% and 13% O(2). The
      multiple inert gas elimination technique was employed to estimate ventilation
      perfusion (Va/Q) distributions and lung diffusing capacity for O(2) (Dl(O(2))).
      There were no significant intergroup differences during exercise breathing 21%
      O(2). During exercise breathing 13% O(2), peak O(2) uptake and Va/Q distributions
      were similar between groups but arterial pH, base excess, and O(2) saturation
      were higher while peak lactate concentration was lower in animals raised at HA
      than at SL. At a given exercise intensity, alveolar-arterial O(2) tension
      gradient (A-aDo(2)) attributable to diffusion limitation was lower while Dlo(2)
      was 12-25% higher in HA-raised animals. Mean systemic arterial blood pressure was
      also lower in HA-raised animals; mean pulmonary arterial pressures were similar.
      We conclude that 5 mo of HA residence during maturation enhances long-term gas
      exchange efficiency and Dl(O(2)) without impacting Va/Q inequality during hypoxic
      exercise at SL.

PMID- 17218429
TI  - Effects of hyperventilation on phosphocreatine kinetics and muscle deoxygenation
      during moderate-intensity plantar flexion exercise.
AB  - The effects of controlled voluntary hyperventilation (Hyp) on phosphocreatine
      (PCr) kinetics and muscle deoxygenation were examined during moderate-intensity
      plantar flexion exercise. Male subjects (n = 7) performed trials consisting of 20
      min rest, 6-min exercise, and 10-min recovery in control [Con; end-tidal Pco(2)
      (Pet(CO(2))) approximately 33 mmHg] and Hyp (Pet(CO(2)) approximately 17 mmHg)
      conditions. Phosphorus-31 magnetic resonance and near-infrared spectroscopy were
      used simultaneously to monitor intramuscular acid-base status, high-energy
      phosphates, and muscle oxygenation. Resting intracellular hydrogen ion
      concentration ([H(+)](i)) was lower (P < 0.05) in Hyp [90 nM (SD 3)] than Con [96
      nM (SD 4)]; however, at end exercise, [H(+)](i) was greater (P < 0.05) in Hyp
      [128 nM (SD 19)] than Con [120 nM (SD 17)]. At rest, [PCr] was not different
      between Con [36 mM (SD 2)] and Hyp [36 mM (SD 1)]. The time constant (tau) of PCr
      breakdown during transition from rest to exercise was greater (P < 0.05) in Hyp
      [39 s (SD 22)] than Con [32 s (SD 22)], and the PCr amplitude was greater (P <
      0.05) in Hyp [26% (SD 4)] than Con [22% (SD 6)]. The deoxyhemoglobin and/or
      deoxymyoglobin (HHb) tau was similar between Hyp [13 s (SD 8)] and Con [10 s (SD
      3)]; however, the amplitude was increased (P < 0.05) in Hyp [40 arbitrary units
      (au) (SD 23)] compared with Con [26 au (SD 17)]. In conclusion, our results
      indicate that Hyp-induced hypocapnia enhanced substrate-level phosphorylation
      during moderate-intensity exercise. In addition, the increased amplitude of the
      HHb response suggests a reduced local muscle perfusion in Hyp compared with Con.

PMID- 17218428
TI  - Use of motor cortex stimulation to measure simultaneously the changes in dynamic
      muscle properties and voluntary activation in human muscles.
AB  - Force responses to transcranial magnetic stimulation of motor cortex (TMS) during
      exercise provide information about voluntary activation and contractile
      properties of the muscle. Here, TMS-generated twitches and muscle relaxation
      during the TMS-evoked silent period were measured in fresh, heated, and fatigued
      muscle. Subjects performed isometric contractions of elbow flexors in two
      studies. Torque and EMG were recorded from elbow flexor and extensor muscles. One
      study (n = 6) measured muscle contraction times and relaxation rates during brief
      maximal and submaximal contractions in fresh and fatigued muscle. Another study
      (n = 7) aimed to 1) assess the reproducibility of muscle contractile properties
      during brief voluntary contractions in fresh muscle, 2) validate the technique
      for contractile properties in passively heated muscle, and 3) apply the technique
      to study contractile properties during sustained maximal voluntary contractions.
      In both studies, muscle contractile properties during voluntary contractions were
      compared with the resting twitch evoked by motor nerve stimulation. Measurement
      of muscle contractile properties during voluntary contractions is reproducible in
      fresh muscle and reveals faster and slower muscle relaxation rates in heated and
      fatigued muscle, respectively. The technique is more sensitive to altered muscle
      state than the traditional motor nerve resting twitch. Use of TMS during
      sustained maximal contractions reveals slowing of muscle contraction and
      relaxation with different time courses and a decline in voluntary activation.
      Voluntary output from the motor cortex becomes insufficient to maintain complete
      activation of muscle, although slowing of muscle contraction and relaxation
      indicates that lower motor unit firing rates are required for fusion of force.

PMID- 17218430
TI  - The extrinsic caspase pathway modulates endotoxin-induced diaphragm contractile
      dysfunction.
AB  - The mechanisms by which infections induce diaphragm dysfunction remain poorly
      understood. The purpose of this study was to determine which caspase pathways
      (i.e., the extrinsic, death receptor-linked caspase-8 pathway, and/or the
      intrinsic, mitochondrial-related caspase-9 pathway) are responsible for endotoxin
      induced diaphragm contractile dysfunction. We determined 1) whether endotoxin
      administration (12 mg/kg IP) to mice induces caspase-8 or -9 activation in the
      diaphragm; 2) whether administration of a caspase-8 inhibitor (N-acetyl-Ile-Glu
      Thr-Asp-CHO, 3 mg/kg iv) or a caspase-9 inhibitor (N-acetyl-Leu-Glu-His-Asp-CHO,
      3 mg/kg iv) blocks endotoxin-induced diaphragmatic weakness and caspase-3
      activation; 3) whether TNF receptor 1-deficient mice have reduced caspase
      activation and diaphragm dysfunction following endotoxin; and 4) whether
      cytokines (TNF-alpha or cytomix, a mixture of TNF-alpha, interleukin-1beta,
      interferon-gamma, and endotoxin) evoke caspase activation in C(2)C(12) myotubes.
      Endotoxin markedly reduced diaphragm force generation (P < 0.001) and induced
      increases in caspase-3 and caspase-8 activity (P < 0.03), but failed to increase
      caspase-9. Inhibitors of caspase-8, but not of caspase-9, prevented endotoxin
      induced reductions in diaphragm force and caspase-3 activation (P < 0.01). Mice
      deficient in TNF receptor 1 also had reduced caspase-8 activation (P < 0.001) and
      less contractile dysfunction (P < 0.01) after endotoxin. Furthermore, incubation
      of C(2)C(12) cells with either TNF-alpha or cytomix elicited significant caspase
      8 activation. The caspase-8 pathway is strongly activated in the diaphragm
      following endotoxin and is responsible for caspase-3 activation and diaphragm
      weakness.

PMID- 17218431
TI  - Novel technology for the provision of power to implantable physiological devices.
AB  - We report the development of a novel technology that enables the wireless
      transmission of sufficient amounts of power to implantable physiological devices.
      The system involves a primary unit generating the magnetic field and a secondary
      pickup unit deriving power from the magnetic field and a power conditioner. The
      inductively coupled system was able to supply a minimum of 20 mW at all locations
      and pickup orientations across a rat cage, although much higher power of up to 10
      W could be achieved. We hypothesized that it would be possible to use this
      technology to record a high-fidelity ECG signal in a conscious rat. A device was
      constructed in which power was utilized to recharge a battery contained within a
      telemetry device recording ECG signal sampled at 2,000 Hz in conscious rats (200
      350 g) living in their home cage. Attributes of the ECG signal (QT, QRS, and PR
      interval) could be obtained with a high degree of accuracy (<1 ms). ECG and heart
      rate changes in response to treatment with the beta blocker propranolol and the
      proarrhythmic alkaloid aconitine were measured. Transmitters were implanted for
      up to 4 mo, and the characteristic circadian variation in heart rate was
      recorded. Such technology allows potentially lifetime monitoring without the need
      for implant refurbishment. The ability to provide suitable power levels to
      implanted devices without concern to the orientation of the device and without
      causing heating provides the basis for the development of new devices to record
      or influence physiological signals in animals or humans over significantly longer
      time periods than can currently be accommodated.

PMID- 17218432
TI  - Point: the lactate paradox does/does not occur during exercise at high altitude.

PMID- 17218433
TI  - Assessing baroreflex sensitivity by the transfer function method: what are we
      really measuring?

PMID- 17218434
TI  - A rat model to study decompression sickness after a trimix dive.

PMID- 17218435
TI  - Modest weight gain is associated with sympathetic neural activation in nonobese
      humans.
AB  - We tested the hypothesis that modest, overfeeding-induced weight gain would
      increase sympathetic neural activity in nonobese humans. Twelve healthy males (23
      +/- 2 years; body mass index, 23.8 +/- 0.7) were overfed approximately 1,000
      kcal/day until a 5-kg weight gain was achieved. Muscle sympathetic nerve activity
      (MSNA, microneurography), blood pressure, body composition (dual energy X-ray
      absorptiometry), and abdominal fat distribution (computed tomography) were
      measured at baseline and following 4 wk of weight stability at each individual's
      elevated body weight. Overfeeding increased body weight (73.5 +/- 3.1 vs. 78.4 +/
      3.2 kg, P < 0.001) and body fat (14.9 +/- 1.2 vs. 18 +/- 1.1 kg, P < 0.001) in
      42 +/- 8 days. Total abdominal fat increased (220 +/- 22 vs. 266 +/- 22 cm(2), P
      < 0.001) with weight gain, due to increases in both subcutaneous (158 +/- 15 vs.
      187 +/- 12 cm(2), P < 0.001) and visceral fat (63 +/- 8 vs. 79 +/- 12 cm(2), P =
      0.004). As hypothesized, weight gain elicited increases in MSNA burst frequency
      (32 +/- 2 vs. 38 +/- 2 burst/min, P = 0.002) and burst incidence (52 +/- 4 vs. 59
      +/- 3 bursts/100 heart beats, P = 0.026). Systolic, but not diastolic blood
      pressure increased significantly with weight gain. The change in MSNA burst
      frequency was correlated with the percent increase in body weight (r = 0.59, P =
      0.022), change in body fat (r = 0.52, P = 0.043) and percent change in body fat
      (r = 0.51, P = 0.045). The results of the current study indicate that modest diet
      induced weight gain elicits sympathetic neural activation in nonobese males.
      These findings may have important implications for understanding the link between
      obesity and hypertension.

PMID- 17218436
TI  - Abnormal glucose homeostasis in adult female rat offspring after intrauterine
      ethanol exposure.
AB  - Adverse events during pregnancy, including prenatal ethanol (EtOH) exposure, are
      associated with insulin-resistant diabetes in male rat offspring, but it is
      unclear whether this is true for female offspring. We investigated whether
      prenatal EtOH exposure alters glucose metabolism in adult female rat offspring
      and whether this is associated with reduced in vivo insulin signaling in skeletal
      muscle. Female Sprague-Dawley rats were given EtOH, 4 g.kg(-1).day(-1) by gavage
      throughout pregnancy. Glucose tolerance test and hyperinsulinemic euglycemic
      clamp were performed, and insulin signaling was investigated in skeletal muscle,
      in adult female offspring. We gave insulin intravenously to these rats and
      determined the association of glucose transporter-4 with plasma membranes, as
      well as the phosphorylation of phosphoinositide-dependent protein kinase-1
      (PDK1), Akt, and PKCzeta. Although EtOH offspring had normal birth weight, they
      were overweight as adults and had fasting hyperglycemia, hyperinsulinemia, and
      reduced insulin-stimulated glucose uptake. After insulin treatment, EtOH-exposed
      rats had decreased membrane glucose transporter-4, PDK1, Akt, and PKCzeta in the
      gastrocnemius muscle, compared with control rats. Insulin stimulation of PDK1,
      Akt, and PKCzeta phosphorylation was also reduced. In addition, the expression of
      the protein tribbles-3 and the phosphatase enzyme activity of phosphatase and
      tensin homolog deleted on chromosome 10 (PTEN), which prevent Akt activation,
      were increased in muscle from EtOH-exposed rats. Female rat offspring exposed to
      EtOH in utero develop insulin-resistant diabetes in association with excessive
      PTEN and tribbles-3 signaling downstream of the phosphatidylinositol 3-kinase
      pathway in skeletal muscle, which may be a mechanism for the abnormal glucose
      tolerance.

PMID- 17218437
TI  - Absence of selective brain cooling in unrestrained baboons exposed to heat.
AB  - To test whether baboons are capable of implementing selective brain cooling, we
      measured, every 5 min, the temperature in their hypothalamus, carotid arterial
      bloodstream, and abdominal cavity. The baboons were unrestrained and exposed to
      22 degrees C for 7 days and then to a cyclic environment with 15 degrees C at
      night and 35 degrees C during the day for a further 7 days. During the latter 7
      days some of the baboons also were exposed to radiant heat during the day. For
      three days, during heat exposure, water was withheld. At no time was the
      hypothalamus cooler than carotid arterial blood, despite brain temperatures above
      40 degrees C. With little variation, the hypothalamus was consistently 0.5
      degrees C warmer than arterial blood. At high body temperatures, the hypothalamus
      was sometimes cooler than the abdomen. Abdominal temperature was more variable
      than arterial blood and tended to exceed arterial blood temperature at higher
      body temperatures. Hypothalamic temperature cooler than a warm abdomen is not
      evidence for selective brain cooling. In species that can implement selective
      brain cooling, the brain is most likely to be cooler than carotid arterial blood
      when an animal is hyperthermic, during heat exposure, and also dehydrated and
      undisturbed by human presence. When we exposed baboons to high ambient
      temperatures while they were water deprived and undisturbed, they never
      implemented selective brain cooling. We conclude that baboons cannot implement
      selective brain cooling and can find no convincing evidence that any primate
      species can do so.

PMID- 17218438
TI  - Effects of hypercapnia and hypocapnia on ventilatory variability and the chaotic
      dynamics of ventilatory flow in humans.
AB  - In humans, lung ventilation exhibits breath-to-breath variability and dynamics
      that are nonlinear, complex, sensitive to initial conditions, unpredictable in
      the long-term, and chaotic. Hypercapnia, as produced by the inhalation of a CO(2)
      enriched gas mixture, stimulates ventilation. Hypocapnia, as produced by
      mechanical hyperventilation, depresses ventilation in animals and in humans
      during sleep, but it does not induce apnea in awake humans. This emphasizes the
      suprapontine influences on ventilatory control. How cortical and subcortical
      commands interfere thus depend on the prevailing CO(2) levels. However, CO(2)
      also influences the variability and complexity of ventilation. This study was
      designed to describe how this occurs and to test the hypothesis that CO(2)
      chemoreceptors are important determinants of ventilatory dynamics. Spontaneous
      ventilatory flow was recorded in eight healthy subjects. Breath-by-breath
      variability was studied through the coefficient of variation of several
      ventilatory variables. Chaos was assessed with the noise titration method (noise
      limit) and characterized with numerical indexes [largest Lyapunov exponent (LLE),
      sensitivity to initial conditions; Kolmogorov-Sinai entropy (KSE),
      unpredictability; and correlation dimension (CD), irregularity]. In all subjects,
      under all conditions, a positive noise limit confirmed chaos. Hypercapnia reduced
      breathing variability, increased LLE (P = 0.0338 vs. normocapnia; P = 0.0018 vs.
      hypocapnia), increased KSE, and slightly reduced CD. Hypocapnia increased
      variability, decreased LLE and KSE, and reduced CD. These results suggest that
      chemoreceptors exert a strong influence on ventilatory variability and
      complexity. However, complexity persists in the quasi-absence of automatic drive.
      Ventilatory variability and complexity could be determined by the interaction
      between the respiratory central pattern generator and suprapontine structures.

PMID- 17218439
TI  - Localized glucoprivation of hindbrain sites elicits corticosterone and glucagon
      secretion.
AB  - Glucose is required for brain energy metabolism. Decerebration, aqueduct
      occlusion, and cannula mapping studies have established that glucose-sensing
      cells capable of eliciting feeding and adrenal medullary responses to
      glucoprivation are localized in the hindbrain. Glucoprivation also evokes
      corticosterone and glucagon secretion, but the location of receptors mediating
      these responses is unknown. To determine whether glucoreceptive sites controlling
      these responses are present in the hindbrain, we administered the antiglycolytic
      agent, 5-d-thioglucose (5TG, 24 microg in 200 nl) into brain stem sites through
      implanted cannulas and examined plasma concentrations of corticosterone and
      glucagon. Both hindbrain and hypothalamic sites were tested. Blood was collected
      remotely from intra-atrial catheters at 0, 30, 60, 90, 120, 180, and 240 min
      after 5TG or control injection. Caudal hindbrain 5TG injections potently
      increased circulating corticosterone and glucagon concentrations. For
      corticosterone, the mean peak response (maximum concentration minus time 0
      concentration) elicited at positive sites (23 of 40 sites) was 391 ng/ml (SE =
      16). For glucagon, the mean peak response at positive sites (27 of 40 sites) was
      46 pg/ml (SE = 6). Glucoprivically evoked glucagon secretion was abolished by the
      ganglionic blocker, hexamethonium, but not by adrenal denervation. Six of twenty
      five hypothalamic sites were positive for corticosterone secretion, yielding
      plasma levels of 279 +/- 23 ng/ml, but none of the hypothalamic injection sites
      elevated glucagon concentrations. Results demonstrate that receptor cells
      responsive to glucose deficit and capable of increasing corticosterone and
      glucagon concentrations exist within the hindbrain, thus further delineating
      central glucoregulatory neural circuitry.

PMID- 17218440
TI  - Presynaptic alpha-adrenoceptors in median preoptic nucleus modulate inhibitory
      neurotransmission from subfornical organ and organum vasculosum lamina
      terminalis.
AB  - The median preoptic nucleus (MnPO) in the lamina terminalis receives a prominent
      catecholaminergic innervation from the dorsomedial and ventrolateral medulla. The
      present investigation used whole cell patch-clamp recordings in rat brain slice
      preparations to evaluate the hypothesis that presynaptic adrenoceptors could
      modulate GABAergic inputs to MnPO neurons. Bath applications of norepinephrine
      (NE; 20-50 microM) induced a prolonged and reversible suppression of inhibitory
      postsynaptic currents (IPSCs) and reduced paired-pulse depression evoked by
      stimulation in the subfornical organ and organum vasculosum lamina terminalis.
      These events were not correlated with any observed changes in membrane
      conductance arising from NE activity at postsynaptic alpha(1)- or alpha(2)
      adrenoceptors. Consistent with a role for presynaptic alpha(2)-adrenoceptors,
      responses were selectively mimicked by an alpha(2)-adrenoceptor agonist (UK
      14304) and blockable with an alpha(2)-adrenoceptor antagonist (idazoxan).
      Although the alpha(1)-adrenoceptor agonist cirazoline and the alpha(1)
      adrenoceptor antagonist prazosin were without effect on these evoked IPSCs, NE
      was noted to increase (via alpha(1)-adrenoceptors) or decrease (via alpha(2)
      adrenoceptors) the frequency of spontaneous and tetrodotoxin-resistant miniature
      IPSCs. Collectively, these observations imply that both presynaptic and
      postsynaptic alpha(1)- and alpha(2)-adrenoceptors in MnPO are capable of
      selective modulation of rapid GABA(A) receptor-mediated inhibitory synaptic
      transmission along the lamina terminalis and therefore likely to exert a
      prominent influence in regulating cell excitability within the MnPO.

PMID- 17218441
TI  - Maternal obesity increases hypothalamic leptin receptor expression and
      sensitivity in juvenile obesity-prone rats.
AB  - In rats selectively bred to develop diet-induced obesity (DIO) or to be diet
      resistant (DR), DIO maternal obesity selectively enhances the development of
      obesity and insulin resistance in their adult offspring. We postulated that the
      interaction between genetic predisposition and factors in the maternal
      environment alter the development of hypothalamic peptide systems involved in
      energy homeostasis regulation. Maternal obesity in the current studies led to
      increased body and fat pad weights and higher leptin and insulin levels in
      postnatal day 16 offspring of both DIO and DR dams. However, by 6 wk of age, most
      of these intergroup differences disappeared and offspring of obese DIO dams had
      unexpected increases in arcuate nucleus leptin receptor mRNA, peripheral insulin
      sensitivity, diet- and leptin-induced brown adipose temperature increase and 24-h
      anorectic response compared with offspring of lean DIO, but not lean DR dams. On
      the other hand, while offspring of obese DIO dams did have the highest
      ventromedial nucleus melanocortin-4 receptor expression, their anorectic and
      brown adipose thermogenic responses to the melanocortin agonist, Melanotan II
      (MTII), did not differ from those of offspring of lean DR or DIO dams. Thus,
      during their rapid growth phase, juvenile offspring of obese DIO dams have
      alterations in their hypothalamic systems regulating energy homeostasis, which
      ameliorates their genetic and perinatally determined predisposition toward leptin
      resistance. Because they later go onto become more obese, it is possible that
      interventions during this time period might prevent the subsequent development of
      obesity.

PMID- 17218442
TI  - Estimating the rate of oxygen consumption during submersion from the heart rate
      of diving animals.
AB  - How animals manage their oxygen stores during diving and other breath-hold
      activities has been a topic of debate among physiologists for decades.
      Specifically, while the behavior of free-ranging diving animals suggests that
      metabolism during submersion must be primarily aerobic in nature, no studies have
      been able to determine their rate of oxygen consumption during submersion
      (Vo(2)d) and hence prove that this is the case. In the present study, we combine
      two previously used techniques and develop a new model to estimate Vo(2)d
      accurately and plausibly in a free-ranging animal and apply it to data for
      macaroni penguins (Eudyptes chrysolophus) as an example. For macaroni penguins at
      least, Vo(2)d can be predicted by measuring heart rate during the dive cycle and
      the subsequent surface interval duration. Including maximum depth of the dive
      improves the accuracy of these predictions. This suggests that energetically
      demanding locomotion events within the dive combine with the differing buoyancy
      and locomotion costs associated with traveling to depth to influence its cost in
      terms of oxygen use. This will in turn effect the duration of the dive and the
      duration of the subsequent recovery period. In the present study, Vo(2)d ranged
      from 4 to 28 ml.min(-1).kg(-1), indicating that, at least as far as aerobic
      metabolism was concerned, macaroni penguins were often hypometabolic, with rates
      of oxygen consumption usually below that for this species resting in water (25.6
      ml.min(-1).kg(-1)) and occasionally lower than that while resting in air (10.3
      ml.min(-1).kg(-1)).

PMID- 17218443
TI  - Exercise training-induced remodeling of paraventricular nucleus (nor)adrenergic
      innervation in normotensive and hypertensive rats.
AB  - Activation of oxytocin (OT)ergic projections from the hypothalamic
      paraventricular nucleus (PVN) to the nucleus tractus solitarii contributes to
      cardiovascular adjustments during exercise training (EXT). Moreover, a deficit in
      this central OTergic pathway is associated with altered cardiovascular function
      in hypertension. Since PVN catecholaminergic inputs, known to be activated during
      EXT, modulate PVN cardiovascular-related functions, we aimed here to determine
      whether remodeling of PVN (nor)adrenergic innervation occurs during EXT and
      whether this phenomenon is affected by hypertension. Confocal immunofluorescence
      microscopy and tract tracing were used to quantify changes in (nor)adrenergic
      innervation density in PVN subnuclei and in identified dorsal vagal complex (DVC)
      projecting neurons (PVN-DVC) in EXT normotensive [Wistar-Kyoto rat (WKY)] and
      hypertensive [spontaneously hypertensive rat (SHR)] rats. In WKY, EXT increased
      the density of PVN dopamine beta-hydroxylase immunoreactivity (DBHir) (160%).
      Furthermore, the number and density of DBHir boutons overlapping PVN-DVC OTergic
      neurons were also increased during EXT (130%), effects that were blunted in SHR.
      Conversely, while DBHir in the medial parvocellular subnucleus (an area enriched
      in corticotropin-releasing hormone neurons) was not changed by EXT in WKY, a
      diminished DBHir was observed in trained SHR. Overall, these data support the
      concept that the PVN (nor)adrenergic innervation undergoes plastic remodeling
      during EXT, an effect that is differentially affected during hypertension. The
      functional implications of PVN (nor)adrenergic remodeling in relation to the
      central peptidergic control of cardiovascular function during EXT are discussed.

PMID- 17218444
TI  - Milnacipran, a serotonin and norepinephrine reuptake inhibitor, induces appetite
      suppressing effects without inducing hypothalamic stress responses in mice.
AB  - Milnacipran, a selective serotonin (5-HT) and norepinephrine (NE) reuptake
      inhibitor, increases extracellular 5-HT and NA levels equally in the central
      nervous system. Here, we report that systemic administration of milnacipran (20
      60 mg/kg) significantly suppressed food intake after fasting in C57BL6J mice. The
      appetite-suppressing effects of milnacipran were sustained for 5 h. Neither
      SB242084, a selective 5-HT2C receptor antagonist, nor SB224289, a selective 5
      HT1B receptor antagonist, reversed the appetite-suppressing effects of
      milnacipran. Milnacipran suppressed food intake and body weight in wild-type mice
      and in A(y) mice, which have ectopic expression of the agouti protein. Moreover,
      milnacipran significantly increased hypothalamic proopiomelanocortin (POMC) and
      cocaine- and amphetamine-regulated transcript (CART) mRNA levels, while having no
      effect on hypothalamic neuropeptide Y, ghrelin, corticotropin-releasing hormone
      (CRH), and suppressor of cytokine signaling-3 mRNA levels. Interestingly,
      milnacipran did not increase plasma corticosterone and blood glucose levels,
      whereas fenfluramine, which inhibits 5-HT reuptake and stimulates 5-HT release,
      significantly increased plasma corticosterone and blood glucose levels in
      association with increased hypothalamic CRH mRNA levels. The appetite-suppressing
      effects of milnacipran had no effects on food intake in food-restricted, wild
      type mice and A(y) mice. On the other hand, fenfluramine suppressed food intake
      in food-restricted wild-type mice, but it had no effects in food-restricted A(y)
      mice. These results suggest that inhibition of 5-HT and NA reuptake induces
      appetite-suppressing effects independent of 5-HT2C and 5-HT1B receptors, and
      increases hypothalamic POMC and CART gene expression without increasing plasma
      corticosterone and blood glucose levels in mice.

PMID- 17218445
TI  - Role of renal sympathetic nerve activity in hypertension induced by chronic
      nitric oxide inhibition.
AB  - Nitric oxide levels are diminished in hypertensive patients, suggesting nitric
      oxide might have an important role to play in the development of hypertension.
      Chronic blockade of nitric oxide leads to hypertension that is sustained
      throughout the period of the blockade in baroreceptor-intact animals. It has been
      suggested that the sympathetic nervous system is involved in the chronic increase
      in blood pressure; however, the evidence is inconclusive. We measured renal
      sympathetic nerve activity and blood pressure via telemetry in rabbits over 7
      days of nitric oxide blockade. Nitric oxide blockade via N(omega)-nitro-L
      arginine methyl ester (L-NAME) in the drinking water (50 mg x kg(-1) x day(-1))
      for 7 days caused a significant increase in arterial pressure (7 +/- 1 mmHg above
      control levels; P < 0.05). While the increase in blood pressure was associated
      with a decrease in heart rate (from 233 +/- 6 beats/min before the L-NAME to 202
      +/- 6 beats/min on day 7), there was no change in renal sympathetic nerve
      activity (94 +/- 4 %baseline levels on day 2 and 96 +/- 5 %baseline levels on day
      7 of L-NAME; baseline nerve activity levels were normalized to the maximum 2 s of
      nerve activity evoked by nasopharyngeal stimulation). The lack of change in renal
      sympathetic nerve activity during the L-NAME-induced hypertension indicates that
      the renal nerves do not mediate the increase in blood pressure in conscious
      rabbits.

PMID- 17218446
TI  - Hemodynamic responses and c-Fos changes associated with hypotensive hemorrhage:
      standardizing a protocol for severe hemorrhage in conscious rats.
AB  - The central mechanisms underlying the transition from compensation to
      decompensation during severe hemorrhage (HEM) are poorly understood. Furthermore,
      a lack of consistency in HEM protocols exists in the current literature. This
      study assessed the cardiovascular response and Fos-like immunoreactivity (FLI) in
      specific brain regions following severe HEM at three rates (2, 1, or 0.5 ml.kg(
      1).min(-1)) in conscious rats. Heart rate (HR) and arterial pressure were
      recorded during the withdrawal of 30% of total blood volume (TBV). Data from
      animals hemorrhaged at the fast (F-HEM, n = 6), intermediate (I-HEM, n = 7), or
      slow (S-HEM, n = 7) rates were compared with saline (SAL, n = 5) and hypotensive
      (hydrazaline-induced, HYDRAZ, n = 5) controls. All HEM rates produced similar
      degrees of hypotension at the time of 30% TBV withdrawal. All HEM rates also
      produced bradycardia, but the change in HR was only significant in the F-HEM and
      I-HEM groups. Associated with I-HEM and F-HEM, but not HYDRAZ treatment were
      significant increases in FLI in the caudal ventrolateral periaqueductal gray
      (PAG), the central lateral nucleus of the rostral parabrachial nucleus, and locus
      coeruleus compared with SAL treatment. I-HEM also induced significant increases
      in FLI in the dorsomedial PAG, A7 region, and the cuneiform nucleus compared with
      SAL. S-HEM did not induce any significant change in FLI. Our results suggest that
      HEM at a rate of 1 ml.kg(-1).min(-1) may be most useful for investigating the
      potential role of the rostral brainstem regions in mediating hemorrhagic
      decompensation in conscious rats.

PMID- 17218447
TI  - Synergistic antimycobacterial activities of sesquiterpene lactones from Laurus
      spp.
AB  - OBJECTIVES: The aim of this study was to determine the antimycobacterial
      potential of laurel oil, its fractions and its two sesquiterpene lactones against
      several mycobacterial strains and clinical isolates, and to establish the
      possibility of occurrence of some synergistic effects between those lactones
      using a modification of the fluorometric Alamar Blue microassay (FMABA). METHODS:
      The in vitro antimycobacterial activity of whole oil and its fractions and pure
      active compounds were determined by FMABA. A bioassay-guided fractionation of the
      traditional preparation of laurel oil from Madeira Islands was performed,
      yielding pure compounds chemically identified by standard procedures. Synergism
      of pure compounds was established by X/Y quotient analysis adapted to FMABA.
      RESULTS: Sesquiterpene lactones, costunolide and dehydrocostuslactone, were the
      compounds responsible for the antimycobacterial activity against Mycobacterium
      tuberculosis H37Rv with MICs of 6.25 and 12.5 mg/L, respectively.
      Antimycobacterial activity against drug-resistant M. tuberculosis clinical
      isolates was better for the mixture than for pure compounds. CONCLUSIONS: Both
      lactones presented synergistic activity, i.e. analysis of relative fluorescence
      units presented an X/Y value <0.5 at a concentration of 1/8 MIC of each compound
      in the combination. Establishment of synergism by FMABA represents another
      application of the microplate Alamar Blue assay.

PMID- 17218448
TI  - Enhanced killing of intracellular multidrug-resistant Mycobacterium tuberculosis
      by compounds that affect the activity of efflux pumps.
AB  - Whereas human neutrophils are effective and efficient killers of bacteria,
      macrophages such as those derived from monocytes are almost devoid of killing
      activity. Nevertheless, monocytes can be transformed into effective killers of
      mycobacteria or staphylococci when exposed to clinical concentrations of a
      phenothiazine or to inhibitors of efflux pumps (reserpine and verapamil), or to
      ouabain, an inhibitor of K(+) transport. Because the rates of multidrug-resistant
      Mycobacterium tuberculosis (MDR-TB) continue to escalate globally, and because no
      new effective drug has been made available for almost 40 years, compounds that
      enhance the killing activity of monocytes against MDR-TB are obviously needed.
      This review covers the specific characteristics of MDR-TB, identifies a variety
      of agents that address these characteristics and therefore have potential for
      managing MDR-TB. Because the mechanism by which these agents enhance the killing
      of intracellular bacteria is important for the intelligent design of new anti
      tubercular agents, the review correlates the mechanisms by which these agents
      manifest their effects. Lastly, a model is presented which describes the
      mechanisms by which distinct efflux pumps of the phagosome-lysosome complex are
      inhibited by agents that are known to inhibit K(+) flux. The model also predicts
      the existence of a K(+) activated exchange (pump) that is probably located in the
      membrane that delineates the lysosome. This putative pump, which is immune to
      inhibitors of K+ flux, is identified as being the cause for the acidification of
      the lysosome thereby activating its hydrolytic enzymes. Because the non-killer
      macrophage can be transformed into an effective killer by a variety of compounds
      that inhibit K(+) transport, perhaps it would be wise to develop drugs that
      enhance the killing activity of these cells inasmuch as this approach would not
      be subject to any resistance, as is the eventual case for conventional
      antibiotics.

PMID- 17218449
TI  - Clarithromycin alone and in combination with ceftriaxone inhibits the production
      of pneumolysin by both macrolide-susceptible and macrolide-resistant strains of
      Streptococcus pneumoniae.
AB  - OBJECTIVES: To investigate the effects of clarithromycin (0.01-0.5 mg/L) alone or
      in combination with ceftriaxone (0.1 and 0.25 mg/L) on pneumolysin production by
      both macrolide-susceptible and -resistant [2 erm(B) positive and 2 mef(A)
      positive] strains of Streptococcus pneumoniae. METHODS: The bacteria were
      cultured for 6 h at 37 degrees C/5% CO(2) in tryptone soy broth, washed,
      enumerated and resuspended to 0.5-3 x 10(8) cfu/mL in tissue culture medium, RPMI
      1640. After 16 h of incubation at 37 degrees C / 5% CO(2), pneumolysin was
      assayed in the bacteria-free supernatants, as well as in lysates, using a
      functional assay based on the influx of calcium into human neutrophils. RESULTS:
      Exposure of not only macrolide-susceptible strains, but also the macrolide
      resistant strains, of S. pneumoniae to sub-MICs of clarithromycin resulted in
      dose-related inhibition of the pneumolysin production, whereas production of the
      toxin was unaffected by ceftriaxone. CONCLUSIONS: These observations demonstrate
      that even in the setting of macrolide resistance the production of pneumolysin, a
      key virulence factor of the pneumococcus, is attenuated by exposure of this
      microbial pathogen to clarithromycin.

PMID- 17218450
TI  - Long-term clinical variation of NT-proBNP in stable chronic heart failure
      patients.
AB  - AIMS: Here, the aim is to assess long-term clinical variation (CV) of N-terminal
      pro-brain natriuretic peptide (NT-proBNP) in stable chronic heart failure (CHF)
      patients. The proposed use of NT-proBNP for monitoring of CHF patients will
      require accurate information about long-term CV of the peptide. METHODS AND
      RESULTS: Medication, biochemical variables, and NYHA class were recorded at 1
      year and 2-year follow-up in patients treated in our heart failure clinic. Only
      patients without changes in medication and the NYHA class who were not
      hospitalized or died in the period from first follow-up to 12 months after the
      second follow-up were included. A total of 78 patients fulfilled the criteria,
      and year-to-year CV was calculated to 30% (median) (range: 0-111%) (% changes
      range: -87 to 397%). Log transformation of NT-proBNP (skewed to the right)
      reduced the year-to-year CV to 4.7% (range: 0-22%) (% changes range: -18 to 38%).
      CONCLUSION: Long-term CV of plasma concentrations of NT-proBNP in stable CHF
      patients is 30%, but the variation is substantial. Therefore, high long-term CV
      of NT-proBNP does not necessarily carry prognostic significance within the
      subsequent 12 months. Plasma concentrations of NT-proBNP followed a lognormal
      distribution, and the low CV of log(NT-proBNP) indicate that NT-proBNP levels are
      constant during stable conditions.

PMID- 17218451
TI  - Remote-controlled catheter ablation of accessory pathways: results from the
      magnetic laboratory.
AB  - AIMS: This study evaluates feasibility, safety, and efficacy of magnetic remote
      controlled accessory pathway (AP) ablation. METHODS AND RESULTS: The novel
      magnetic navigation system (MNS) (Niobe, Stereotaxis) creates a steerable
      magnetic field (0.08 T) controlling the distal magnetic tip of an ablation
      catheter. In conjunction with a catheter advancer system (Cardiodrive,
      Stereotaxis) remote catheter ablation is enabled. Conventional electrophysiology
      study identified AP conduction in 59 patients (37 males, 36+/-14 years, 60 APs).
      First generation 1-magnet tip (1-M) (group I, n=18), second generation bipolar 3
      magnet tip (3-M) (group II, n=27), and third generation quadripolar 3-magnet tip
      catheters (3-M quad.) (group III, n=14) were used for magnetic remote-controlled
      ablation. Successful AP ablation was achieved in 67% (group I), 85% (group II),
      and 92% (group III). A significant decrease of median [IQR: Q1-Q3] fluoroscopy
      time and dosage was observed: 21.2 [12.1-33.8] min, 1110 [395-3234] microGym2
      (group I); 6.5 [4.4-15.4] min, 290 [129-489] microGym2 (group II), and 4.9 [3.4
      8.0] min, 129 [74-270] microGym2 (group III). Mean procedure time (217+/-67 min;
      182+/-68 min, and 172+/-90 min) significantly decreased in group III. Median
      number [Q1-Q3] of radiofrequency current applications in groups I, II, and III
      was 4 [2-9], 4 [2-6], and 2 [2-4], respectively. No complications occurred.
      CONCLUSION: Remote AP ablation is safe and feasible using the novel MNS.
      Introduction of the 3-magnet quadripolar ablation catheter significantly improved
      the efficacy of the procedure.

PMID- 17218452
TI  - Importance of collateral circulation in coronary heart disease.
AB  - AIMS: Collateral arteries are a common but inconsistent finding in coronary heart
      disease (CHD). We endeavoured to review the methods for coronary artery
      collateral assessment, the predictors and clinical importance of collateral blood
      flow, and the potential for therapeutic augmentation of collateral anastomoses.
      METHODS AND RESULTS: While many methods have been used to assess collateral blood
      flow only a few have been formally validated. Collateral flow index, as
      determined by measurement of intra-coronary pressure or flow velocity, is the
      most robust measure of collateral flow. These techniques have led to important
      advances in our understanding of collateral artery function. Coronary collateral
      arteries may prevent myocardial ischaemia in healthy subjects and in patients
      with CHD. A functional collateral circulation may lead to reduced ischaemia,
      preservation of ventricular function, and an improved prognosis. Recent trials
      have demonstrated that vascular progenitor cell therapies may improve ventricular
      function following acute myocardial infarction, raising the possibility of
      effective biological treatments to improve myocardial blood flow and prognosis in
      CHD. CONCLUSIONS: Coronary collateral anastomoses represent a prognostically
      important adaptive response in patients with CHD. Therapeutic augmentation of
      collaterals with emerging biological therapies represents a desirable goal for
      treating CHD patients.

PMID- 17218453
TI  - Combinatorial approach for ferroelectric material libraries prepared by liquid
      source misted chemical deposition method.
AB  - Combinatorial approach for discovering novel functional materials in the huge
      diversity of chemical composition and processing conditions has become more
      important for breakthrough in thin film electronic and energy-conversion devices.
      The efficiency of combinatorial method depends on the preparation of a reliable
      high-density composition thin-film library. The physico-chemical properties of
      each sample on the library should be similar to those of the corresponding
      samples prepared by one-by-one conventional methods. We successfully developed
      the combinatorial liquid source misted chemical deposition (LSMCD) method and
      demonstrated its validity in screening the chemical composition of
      Bi3.75LaxCe0.25-xTi3O12 (BLCT) for high remanent polarization (Pr). LSMCD is a
      cheap promising combinatorial screening tool. It can control the composition up
      to ppm level and produce homogeneous multicomponent library. LSMCD method allows
      us to prepare BLCT thin-film library at the variation of 0.4 mol% of La. Maximum
      2Pr is 35 microC/cm-2 at x=0.21. The intensity of (117) XRD peak is
      quantitatively related to 2Pr. Newly developed scanning piezoelectric deformation
      measurement for nano-sized samples using scanning probe microscope (SPM) is also
      found out to be reliable for determining the relative ranking of Pr value
      rapidly.

PMID- 17218455
TI  - Upregulation of forces and morphogenic asymmetries in dorsal closure during
      Drosophila development.
AB  - Tissue dynamics during dorsal closure, a stage of Drosophila development, provide
      a model system for cell sheet morphogenesis and wound healing. Dorsal closure is
      characterized by complex cell sheet movements, driven by multiple tissue specific
      forces, which are coordinated in space, synchronized in time, and resilient to UV
      laser perturbations. The mechanisms responsible for these attributes are not
      fully understood. We measured spatial, kinematic, and dynamic antero-posterior
      asymmetries to biophysically characterize both resiliency to laser perturbations
      and failure of closure in mutant embryos and compared them to natural asymmetries
      in unperturbed, wild-type closure. We quantified and mathematically modeled two
      processes that are upregulated to provide resiliency--contractility of the
      amnioserosa and formation of a seam between advancing epidermal sheets, i.e.,
      zipping. Both processes are spatially removed from the laser-targeted site,
      indicating they are not a local response to laser-induced wounding and suggesting
      mechanosensitive and/or chemosensitive mechanisms for upregulation. In mutant
      embryos, tissue junctions initially fail at the anterior end indicating
      inhomogeneous mechanical stresses attributable to head involution, another
      developmental process that occurs concomitant with the end stages of closure.
      Asymmetries in these mutants are reversed compared to wild-type, and
      inhomogeneous stresses may cause asymmetries in wild-type closure.

PMID- 17218456
TI  - Classical versus stochastic kinetics modeling of biochemical reaction systems.
AB  - We study fundamental relationships between classical and stochastic chemical
      kinetics for general biochemical systems with elementary reactions. Analytical
      and numerical investigations show that intrinsic fluctuations may qualitatively
      and quantitatively affect both transient and stationary system behavior. Thus, we
      provide a theoretical understanding of the role that intrinsic fluctuations may
      play in inducing biochemical function. The mean concentration dynamics are
      governed by differential equations that are similar to the ones of classical
      chemical kinetics, expressed in terms of the stoichiometry matrix and time
      dependent fluxes. However, each flux is decomposed into a macroscopic term, which
      accounts for the effect of mean reactant concentrations on the rate of product
      synthesis, and a mesoscopic term, which accounts for the effect of statistical
      correlations among interacting reactions. We demonstrate that the ability of a
      model to account for phenomena induced by intrinsic fluctuations may be seriously
      compromised if we do not include the mesoscopic fluxes. Unfortunately,
      computation of fluxes and mean concentration dynamics requires intensive Monte
      Carlo simulation. To circumvent the computational expense, we employ a moment
      closure scheme, which leads to differential equations that can be solved by
      standard numerical techniques to obtain more accurate approximations of fluxes
      and mean concentration dynamics than the ones obtained with the classical
      approach.

PMID- 17218454
TI  - Anisotropy and temperature dependence of myoglobin translational diffusion in
      myocardium: implication for oxygen transport and cellular architecture.
AB  - Pulsed field gradient NMR methods have determined the temperature-dependent
      diffusion of myoglobin (Mb) in perfused rat myocardium. Mb diffuses with an
      averaged translational diffusion coefficient (DMb) of 4.24-8.37x10(-7)cm2/s from
      22 degrees C to 40 degrees C and shows no orientation preference over a root mean
      square displacement of 2.5-3.5 microm. The DMb agrees with the value predicted by
      rotational diffusion measurements. Based on the DMb, the equipoise diffusion PO2,
      the PO2 in which Mb-facilitated and free O2 diffusion contribute equally to the
      O2 flux, varies from 2.72 to 0.15 in myocardium and from 7.27 to 4.24 mmHg in
      skeletal muscle. Given the basal PO2 of approximately 10 mmHg, the Mb
      contribution to O2 transport appears insignificant in myocardium. In skeletal
      muscle, Mb-facilitated diffusion begins to contribute significantly only when the
      PO2 approaches the P50. In marine mammals, the high Mb concentration confers a
      predominant role for Mb in intracellular O2 transport under all physiological
      conditions. The Q10 of the DMb ranges from 1.3 to 1.6. The Mb diffusion data
      indicate that the postulated gel network in the cell must have a minimum
      percolation cutoff size exceeding 17.5 A and does not impose tortuosity within
      the diffusion root mean-square displacement. Moreover, the similar Q10 for the
      DMb of solution versus cell Mb suggests that any temperature-dependent alteration
      of the postulated cell matrix does not significantly affect protein mobility.

PMID- 17218458
TI  - Stick-and-diffuse and caged diffusion: a comparison of two models of synaptic
      vesicle dynamics.
AB  - Two models were recently proposed to enable us to understand the dynamics of
      synaptic vesicles in hippocampal neurons. In the caged diffusion model, the
      vesicles diffuse in small circular cages located randomly in the bouton, while in
      the stick-and-diffuse model the vesicles bind and release from a cellular
      cytomatrix. In this article, we obtain analytic expressions for the fluorescence
      correlation spectroscopy (FCS) autocorrelation function for the two models and
      test their predictions against our earlier FCS measurements of the vesicle
      dynamics. We find that the stick-and-diffuse model agrees much better with the
      experiment. We find also that, due to the slow dynamics of the vesicles, the
      finite experimental integration time has an important effect on the FCS
      autocorrelation function and demonstrate its effect for the different models. The
      two models of the dynamics are also relevant to other cellular environments where
      mobile species undergo slow diffusionlike motion in restricted spaces or bind and
      release from a stationary substrate.

PMID- 17218457
TI  - A generalized born implicit-membrane representation compared to experimental
      insertion free energies.
AB  - An implicit-membrane representation based on the generalized Born theory of
      solvation has been developed. The method was parameterized against the water-to
      cyclohexane insertion free energies of hydrophobic side-chain analogs.
      Subsequently, the membrane was compared with experimental data from translocon
      inserted polypeptides and validated by comparison with an independent dataset of
      six membrane-associated peptides and eight integral membrane proteins of known
      structure and orientation. Comparison of the insertion energy of alpha-helical
      model peptides with the experimental values from the biological hydrophobicity
      scale of Hessa et al. gave a correlation of 93% with a mean unsigned error of
      0.64 kcal/mol, when charged residues were ignored. The membrane insertion energy
      was found to be dependent on residue position. This effect is particularly
      pronounced for charged and polar residues, which strongly prefer interfacial
      locations. All integral membrane proteins investigated orient and insert
      correctly into the implicit-membrane model. Remarkably, the membrane model
      correctly predicts a partially inserted configuration for the monotopic membrane
      protein cyclooxygenase, matching experimental and theoretical predictions. To
      test the applicability and usefulness of the implicit-membrane method, molecular
      simulations of influenza A M2 as well as the glycophorin A dimer were performed.
      Both systems remain structurally stable and integrated into the membrane.

PMID- 17218460
TI  - A molecular dynamics study of the ligand release path in yeast cytosine
      deaminase.
AB  - Yeast cytosine deaminase, a zinc metalloenzyme, catalyzes the deamination of
      cytosine to uracil. Experimental and computational evidence indicates that the
      rate-limiting step is product release, instead of the chemical reaction step. In
      this work, we use molecular dynamics to suggest ligand exit paths. Simulation at
      300 K shows that the active site is well protected by the C-terminal helix
      (residues 150-158) and F-114 loop (residues 111-117) and that on the molecular
      dynamics timescale water does not flow in or out of the active site. In contrast,
      simulation at 320 K shows a significant increase in flexibility of the C-terminal
      helix and F-114 loop. The motions of these two regions at 320 K open the active
      site and permit water molecules to diffuse into and out of the active site
      through two paths with one much more favored than the other. Cytosine is pushed
      out of the active site by a restraint method in two directions specified by these
      two paths. In path 1 the required motion of the protein is local-involving only
      the C-terminal helix and F-114 loop-and two residues, F-114 and I-156, are
      identified that have to be moved away to let cytosine out; whereas in path 2, the
      protein has to rearrange itself much more extensively, and the changes are also
      much larger compared to the path 1 simulation.

PMID- 17218459
TI  - Unusual thermal stability of RNA/[RP-PS]-DNA/RNA triplexes containing a
      homopurine DNA strand.
AB  - Homopurine deoxyribonucleoside phosphorothioates, as short as hexanucleotides and
      possessing all internucleotide linkages of RP configuration, form a triple helix
      with two RNA or 2'-OMe-RNA strands, with Watson-Crick and Hoogsteen
      complementarity. Melting temperature and fluorescence quenching experiments
      strongly suggest that the Hoogsteen RNA strand is parallel to the homopurine [RP
      PS]-oligomer. Remarkably, these triplexes are thermally more stable than
      complexes formed by unmodified homopurine DNA molecules of the same sequence. The
      triplexes formed by phosphorothioate DNA dodecamers containing 4-6 dG residues
      are thermally stable at pH 7.4, although their stability increases significantly
      at pH 5.3. FTIR measurements suggest participation of the C2-carbonyl group of
      the pyrimidines in the stabilization of the triplex structure. Formation of
      triple-helix complexes with exogenously delivered PS-oligos may become useful for
      the reduction of RNA accessibility in vivo and, hence, selective
      suppression/inhibition of the translation process.

PMID- 17218462
TI  - How alcohol chain-length and concentration modulate hydrogen bond formation in a
      lipid bilayer.
AB  - Molecular dynamics simulations are used to measure the change in properties of a
      hydrated dipalmitoylphosphatidylcholine bilayer when solvated with ethanol,
      propanol, and butanol solutions. There are eight oxygen atoms in
      dipalmitoylphosphatidylcholine that serve as hydrogen bond acceptors, and two of
      the oxygen atoms participate in hydrogen bonds that exist for significantly
      longer time spans than the hydrogen bonds at the other six oxygen atoms for the
      ethanol and propanol simulations. We conclude that this is caused by the lipid
      head group conformation, where the two favored hydrogen-bonding sites are
      partially protected between the head group choline and the sn-2 carbonyl oxygen.
      We find that the concentration of the alcohol in the ethanol and propanol
      simulations does not have a significant influence on the locations of the
      alcohol/lipid hydrogen bonds, whereas the concentration does impact the locations
      of the butanol/lipid hydrogen bonds. The concentration is important for all three
      alcohol types when the lipid chain order is examined, where, with the exception
      of the high-concentration butanol simulation, the alcohol molecules having the
      longest hydrogen-bonding relaxation times at the favored carbonyl oxygen acceptor
      sites also have the largest order in the upper chain region. The lipid behavior
      in the high-concentration butanol simulation differs significantly from that of
      the other alcohol concentrations in the order parameter, head group rotational
      relaxation time, and alcohol/lipid hydrogen-bonding location and relaxation time.
      This appears to be the result of the system being very near to a phase
      transition, and one occurrence of lipid flip-flop is seen at this concentration.

PMID- 17218461
TI  - Different effects of trifluoroethanol and glycerol on the stability of
      tropomyosin helices and the head-to-tail complex.
AB  - Tropomyosin (Tm) is a dimeric coiled-coil protein, composed of 284 amino acids
      (410 A), that forms linear homopolymers through head-to-tail interactions at low
      ionic strength. The head-to-tail complex involves the overlap of approximately
      nine N-terminal residues of one molecule with nine C-terminal residues of another
      Tm molecule. In this study, we investigate the influence of 2,2,2
      trifluoroethanol (TFE) and glycerol on the stability of recombinant Tm fragments
      (ASTm1-142, Tm143-284(5OHW269)) and of the dimeric head-to-tail complex formed by
      the association of these two fragments. The C-terminal fragment (Tm143
      284(5OHW269)) contains a 5-hydroxytryptophan (5OHW) probe at position 269 whose
      fluorescence is sensitive to the head-to-tail interaction and allows us to
      accompany titrations of Tm143-284(5OHW269) with ASTm1-142 to calculate the
      dissociation constant (Kd) and the interaction energy at TFE and glycerol
      concentrations between 0% and 15%. We observe that TFE, but not glycerol, reduces
      the stability of the head-to-tail complex. Thermal denaturation experiments also
      showed that the head-to-tail complex increases the overall conformational
      stability of the Tm fragments. Urea and thermal denaturation assays demonstrated
      that both TFE and glycerol increase the stability of the isolated N- and C
      terminal fragments; however, only TFE caused a significant reduction in the
      cooperativity of unfolding these fragments. Our results show that these two
      cosolvents stabilize the structures of individual Tm fragments in different
      manners and that these differences may be related to their opposing effects on
      head-to-tail complex formation.

PMID- 17218463
TI  - Force-induced DNA slippage.
AB  - DNA containing repetitive sequences displays richer dynamics than heterogeneous
      sequences. In the genome the number of repeat units of repetitive sequences,
      known as microsatellites, may vary during replication by DNA slippage and their
      expansion gives rise to serious disorders. We studied the mechanical properties
      of repetitive DNA using dynamic force spectroscopy and found striking differences
      compared with ordinary heterogeneous sequences. Repetitive sequences dissociate
      at lower forces and elongate above a certain threshold force. This yield force
      was found to be rate dependent. Following the rapid stretching of the DNA duplex,
      the applied force relaxes by stepwise elongation of this duplex. Conversely,
      contraction of the DNA duplex can be observed at low forces. The stepwise
      elongation and shortening is initiated by single slippage events, and single
      molecule experiments might help to explain the molecular mechanisms of
      microsatellites formation. In addition to the biological importance, the
      remarkable properties of repetitive DNA can be useful for different
      nanomechanical applications.

PMID- 17218464
TI  - Neutrophil traction stresses are concentrated in the uropod during migration.
AB  - We find that in contrast to strongly adherent, slow moving cells such as
      fibroblasts, neutrophils exert contractile stresses largely in the rear of the
      cell (uropod) relative to the direction of motion. Rather than the leading edge
      pulling the cell, the rear is both anchoring the cell and the area in which the
      contractile forces are concentrated. These tractions rapidly reorient themselves
      during a turn, on a timescale of seconds to minutes, and their repositioning
      precedes and sets the direction of motion during a turn. We find the total
      average root mean-squared traction force to be 28+/-10 nN during chemokinesis,
      and 67+/-10 nN during chemotaxis. We hypothesize that the contraction forces in
      the back of the neutrophil not only break uropodial adhesive contacts but also
      create a rearward squeezing contractility, as seen in amoeboid or amoeboidlike
      cells and the formation of blebs in cells, causing a flow of intracellular
      material to the fluidlike lamellipod. Our findings suggest an entirely new model
      of neutrophil locomotion.

PMID- 17218465
TI  - Temperature dependence of fast dynamics in proteins.
AB  - The temperature dependence of the internal dynamics of recombinant human
      ubiquitin has been measured using solution NMR relaxation techniques. Nitrogen-15
      relaxation has been employed to obtain a measure of the amplitude of
      subnanosecond motion at amide N-H sites in the protein. Deuterium relaxation has
      been used to obtain a measure of the amplitude of motion of methyl-groups in
      amino-acid side chains. Data was obtained between 5 and 55 degrees C. The
      majority of amide N-H and methyl groups show a roughly linear (R(2)>0.75)
      temperature dependence of the associated Lipari-Szabo model-free squared
      generalized-order parameter (O(2)) describing the amplitude of motion.
      Interestingly, for those sites showing a linear response, the temperature
      dependence of the backbone is distinct from that of the methyl-bearing side
      chains with the former being characterized by a significantly larger Lambda
      value, where Lambda is defined as d ln(1 - O)/d lnT. These results are comparable
      to the sole previous such study of the temperature dependence of protein motion
      obtained for a calmodulin-peptide complex. This suggests that the distinction
      between the main chain and methyl-bearing side chains may be general. Insight
      into the temperature dependence is gathered from a simple two-state step
      potential model.

PMID- 17218466
TI  - Mechanism of the cell-penetrating peptide transportan 10 permeation of lipid
      bilayers.
AB  - The mechanism of the interaction between the cell-penetrating peptide transportan
      10 (tp10) and phospholipid membranes was investigated. Tp10 induces graded
      release of the contents of phospholipid vesicles. The kinetics of peptide
      association with vesicles and peptide-induced dye efflux from the vesicle lumen
      were examined experimentally by stopped-flow fluorescence. The experimental
      kinetics were analyzed by directly fitting to the data the numerical solution of
      mathematical kinetic models. A very good global fit was obtained using a model in
      which tp10 binds to the membrane surface and perturbs it because of the mass
      imbalance thus created across the bilayer. The perturbed bilayer state allows
      peptide monomers to insert transiently into its hydrophobic core and cross the
      membrane, until the peptide mass imbalance is dissipated. In that transient state
      tp10 "catalyzes" dye efflux from the vesicle lumen. These conclusions are
      consistent with recent reports that used molecular dynamics simulations to study
      the interactions between peptide antimicrobials and phospholipid bilayers. A
      thermodynamic analysis of tp10 binding and insertion in the bilayer using water
      membrane transfer hydrophobicity scales is entirely consistent with the model
      proposed. A small bilayer perturbation is both necessary and sufficient to
      achieve very good agreement with the model, indicating that the role of the
      lipids must be included to understand the mechanism of cell-penetrating and
      antimicrobial peptides.

PMID- 17218467
TI  - Investigation of domain formation in sphingomyelin/cholesterol/POPC mixtures by
      fluorescence resonance energy transfer and Monte Carlo simulations.
AB  - We have recently proposed a phase diagram for mixtures of porcine brain
      sphingomyelin (BSM), cholesterol (Chol), and 1-palmitoyl-2-oleoyl
      phosphatidylcholine (POPC) on the basis of kinetics of carboxyfluorescein efflux
      induced by the amphipathic peptide delta-lysin. Although that study indicated the
      existence of domains, phase separations in the micrometer scale have not been
      observed by fluorescence microscopy in BSM/Chol/POPC mixtures, though they have
      for some other sphingomyelins (SM). Here we examine the same BSM/Chol/POPC system
      by a combination of fluorescence resonance energy transfer (FRET) and Monte Carlo
      simulations. The results clearly demonstrate that domains are formed in this
      system. Comparison of the FRET experimental data with the computer simulations
      allows the estimate of lipid-lipid interaction Gibbs energies between SM/Chol,
      SM/POPC, and Chol/POPC. The latter two interactions are weakly repulsive, but the
      interaction between SM and Chol is favorable. Furthermore, those three unlike
      lipid interaction parameters between the three possible lipid pairs are
      sufficient for the existence of a closed loop in the ternary phase diagram,
      without the need to involve multibody interactions. The calculations also
      indicate that the largest POPC domains contain several thousand lipids,
      corresponding to linear sizes of the order of a few hundred nanometers.

PMID- 17218468
TI  - Effect of surface treatment on diffusion and domain formation in supported lipid
      bilayers.
AB  - Supported lipid bilayers are widely used as model systems due to their
      robustness. Due to the solid support, the properties of supported lipid bilayers
      are different from those of freestanding bilayers. In this article, we examine
      whether different surface treatments affect the properties of supported lipid
      bilayers. It will be shown that depending on the treatment method, the diffusion
      of the lipids can be adjusted approximately threefold without altering the
      composition. Additionally, as the bilayer-support interaction decreases, it
      becomes easier to form coexisting liquid-ordered and liquid-disordered domains.
      The physical/chemical alterations that result from the different treatment
      methods will be discussed.

PMID- 17218469
TI  - Binding of Ca2+ to glutamic acid-rich polypeptides from the rod outer segment.
AB  - Rod photoreceptors contain three different glutamic acid-rich proteins (GARPs)
      that have been proposed to control the propagation of Ca(2+) from the site of its
      entry at the cyclic nucleotide-gated channel to the cytosol of the outer segment.
      We tested this hypothesis by measuring the binding of Ca(2+) to the following
      five constructs related to GARPs of rod photoreceptors: a 32-mer peptide
      containing 22 carboxylate groups, polyglutamic acid, a recombinant segment
      comprising 73 carboxylate groups (GLU), GARP1, and GARP2. Ca(2+) binding was
      investigated by means of a Ca(2+)-sensitive electrode. In all cases, Ca(2+) binds
      with low affinity; the half-maximum binding constant K(1/2) ranges from 6 to 16
      mM. The binding stoichiometry between Ca(2+) ions and carboxylic groups is
      approximately 1:1; an exception is GARP2, where a binding stoichiometry of
      approximately 1:2 was found. Hydrodynamic radii of 1.6, 2.8, 3.3, 5.7, and 6.7 nm
      were determined by dynamic light scattering for the 32-mer, polyglutamic acid,
      GLU, GARP2, and GARP1 constructs, respectively. These results suggest that the
      peptides as well as GARP1 and GARP2 do not adopt compact globular structures. We
      conclude that the structures should be regarded as loose coils with low-affinity,
      high-capacity Ca(2+) binding.

PMID- 17218470
TI  - Prenatal testosterone exposure permanently masculinizes anogenital distance,
      nipple development, and reproductive tract morphology in female Sprague-Dawley
      rats.
AB  - In mammals, abnormal increases in fetal androgens disrupt normal development of
      the female phenotype. Due to the recent concern regarding environmental androgen
      active chemicals, there is a need to identify sources of fetal androgen variation
      and sensitive developmental markers for androgenic activity in female rats.
      Anogenital distances (AGD), nipple retention, reproductive tract, and external
      genitalia are morphological parameters organized by prenatal androgens and are
      predictive of altered masculinized/defeminized phenotype in adult female mice and
      rats. The objectives of this study were to (1) characterize the natural prenatal
      androgen environment of rats including the magnitude of the intrauterine position
      (IUP) effect, (2) characterize the permanent effects of prenatal androgen
      exposure on female rats, and (3) determine the ability of AGD and areolas to
      predict these permanent androgenic alterations in female rats. Untreated male
      fetal rats had higher tissue testosterone (T) concentrations than females in the
      amniotic fluid, reproductive tract, gonad, and fetal body. The intrauterine
      position (IUP) of male and female fetuses did not affect T concentrations or AGD
      in male or female rats at gestational day (GD) 22. Female offspring exposed to 0,
      1.5, and 2.5 mg/kg/day testosterone propionate (TP) on GDs 14-18 displayed
      increased AGD at postnatal day (PND) 2 and decreased nipples at PND 13 and as
      adults. TP-induced changes in neonatal AGD and infant areola number were reliable
      indicators of permanently altered adult phenotype in female rats. Further,
      females in the two high-dose groups displayed increased incidences of external
      genital malformations and the presence of prostatic tissue, not normally found in
      female rats.

PMID- 17218471
TI  - Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in
      adipose tissue.
AB  - Triacylglycerol (TAG) stored in adipose tissue can be rapidly mobilized by the
      hydrolytic action of lipases, with the release of fatty acids (FA) that are used
      by other tissues during times of energy deprivation. Unlike synthesis of TAG,
      which occurs not only in adipose tissue but also in other tissues such as liver
      for very-low-density lipoprotein formation, hydrolysis of TAG, lipolysis,
      predominantly occurs in adipose tissue. Until recently, hormone-sensitive lipase
      was considered to be the key rate-limiting enzyme responsible for regulating TAG
      mobilization. However, recent studies on hormone-sensitive lipase-null mice have
      challenged such a concept. A novel lipase named desnutrin/ATGL has been recently
      discovered to play a key role in lipolysis in adipocytes. Lipolysis is under
      tight hormonal regulation. Although opposing regulation of lipolysis in adipose
      tissue by insulin and catecholamines is well understood, autocrine/paracrine
      factors may also participate in its regulation. Intricate cooperation of these
      endocrine and autocrine/paracrine factors leads to a fine regulation of lipolysis
      in adipocytes, needed for energy homeostasis. In this review, we summarize and
      discuss the recent progress made in the regulation of adipocyte lipolysis.

PMID- 17218472
TI  - Increased gastric expression of MMP-7 in hypergastrinemia and significance for
      epithelial-mesenchymal signaling.
AB  - Chronic hypergastrinemia is associated with enterochromaffin-like (ECL) cell
      hyperplasia, which may progress to gastric carcinoid tumors. The latter consists
      of epithelial cells and stroma, and both compartments usually regress after
      normalization of hypergastrinemia. We previously showed that matrix
      metalloproteinase (MMP)-7 in gastric epithelial cells was upregulated by
      Helicobacter pylori and described MMP-7-dependent reciprocal signaling between
      the epithelium and a key stromal cell type, the myofibroblast. Here, we describe
      the regulation of gastric MMP-7 by gastrin and the potential significance for
      recruiting and maintaining myofibroblast populations. Biopsies of the gastric
      corpus and ECL cell carcinoid tumors were obtained from hypergastrinemic
      patients. Western blot analysis, ELISA, immunohistochemistry, and promoter
      luciferase (luc) reporter assays were used to study MMP-7 expression. Gastric
      myofibroblasts were identified by alpha-smooth muscle actin (alpha-SMA)
      expression, and the effects of MMP-7 on myofibroblast proliferation were
      investigated. In hypergastrinemic patients, there was an increased abundance of
      MMP-7 and alpha-SMA in gastric corpus biopsies and ECL cell carcinoid tumors. In
      the latter, MMP-7 was localized to ECL cells but not stromal cells, which were
      nevertheless well represented. Gastrin stimulated MMP-7-luc expression in both
      AGS-G(R) and primary human gastric epithelial cells. Conditioned medium from
      gastrin-treated human gastric glands stimulated myofibroblast proliferation,
      which was inhibited by neutralizing antibodies to MMP-7. MMP-7 increased the
      proliferation of myofibroblasts via the MAPK and phosphatidylinositol 3-kinase
      (PI3K) pathways. In conclusion, stimulation of gastric MMP-7 by elevated plasma
      gastrin may activate epithelial-mesenchymal signaling pathways regulating
      myofibroblast function via MAPK and PI3K pathways and contribute to stromal
      deposition in ECL cell carcinoid tumors.

PMID- 17218474
TI  - Mechanisms underlying nutrient-induced segmentation in isolated guinea pig small
      intestine.
AB  - Mechanisms underlying nutrient-induced segmentation within the gut are not well
      understood. We have shown that decanoic acid and some amino acids induce neurally
      dependent segmentation in guinea pig small intestine in vitro. This study
      examined the neural mechanisms underlying segmentation in the circular muscle and
      whether the timing of segmentation contractions also depends on slow waves.
      Decanoic acid (1 mM) was infused into the lumen of guinea pig duodenum and
      jejunum. Video imaging was used to monitor intestinal diameter as a function of
      both longitudinal position and time. Circular muscle electrical activity was
      recorded by using suction electrodes. Recordings from sites of segmenting
      contractions showed they are always associated with excitatory junction
      potentials leading to action potentials. Recordings from sites oral and anal to
      segmenting contractions revealed inhibitory junction potentials that were time
      locked to those contractions. Slow waves were never observed underlying
      segmenting contractions. In paralyzed preparations, intracellular recording
      revealed that slow-wave frequency was highly consistent at 19.5 (SD 1.4) cycles
      per minute (c/min) in duodenum and 16.6 (SD 1.1) c/min in jejunum. By contrast,
      the frequencies of segmenting contractions varied widely (duodenum: 3.6-28.8
      c/min, median 10.8 c/min; jejunum: 3.0-27.0 c/min, median 7.8 c/min) and
      sometimes exceeded slow-wave frequencies for that region. Thus nutrient-induced
      segmentation contractions in guinea pig small intestine do not depend on slow
      wave activity. Rather they result from a neural circuit producing rhythmic
      localized activity in excitatory motor neurons, while simultaneously activating
      surrounding inhibitory motor neurons.

PMID- 17218473
TI  - Increased arginase activity and endothelial dysfunction in human inflammatory
      bowel disease.
AB  - Nitric oxide (.NO) generation from conversion of l-arginine to citrulline by
      nitric oxide synthase isoforms plays a critical role in vascular homeostasis.
      Loss of .NO is linked to vascular pathophysiology and is decreased in chronically
      inflamed gut blood vessels in inflammatory bowel disease (IBD; Crohn's disease
      and ulcerative colitis). Mechanisms underlying decreased .NO production in IBD
      gut microvessels are not fully characterized. Loss of .NO generation may result
      from increased arginase (AR) activity, which enzymatically competes with nitric
      oxide synthase for the common substrate l-arginine. We characterized AR
      expression in IBD microvessels and endothelial cells and its contribution to
      decreased .NO production. AR expression was assessed in resected gut tissues and
      human intestinal microvascular endothelial cells (HIMEC). AR expression
      significantly increased in both ulcerative colitis and Crohn's disease
      microvessels and submucosal tissues compared with normal. TNF
      alpha/lipopolysaccharide increased AR activity, mRNA and protein expression in
      HIMEC in a time-dependent fashion. RhoA/ROCK pathway, a negative regulator of .NO
      generation in endothelial cells, was examined. The RhoA inhibitor C3 exoenzyme
      and the ROCK inhibitor Y-27632 both attenuated TNF-alpha/lipopolysaccharide
      induced MAPK activation and blocked AR expression in HIMEC. A significantly
      higher AR activity and increased RhoA activity were observed in IBD submucosal
      tissues surrounding microvessels compared with normal control gut tissue.
      Functionally, inhibition of AR activity decreased leukocyte binding to HIMEC in
      an adhesion assay. Loss of .NO production in IBD microvessels is linked to
      enhanced levels of AR in intestinal endothelial cells exposed to chronic
      inflammation in vivo.

PMID- 17218475
TI  - Effect of CP-96,345 on the expression of adhesion molecules in acute pancreatitis
      in mice.
AB  - We investigated the effect of a specific neurokinin-1 receptor (NK1R) antagonist,
      CP-96,345, on the regulation of the expression of adhesion molecules ICAM-1, VCAM
      1, E-selectin, and P-selectin as well as leukocyte recruitment during acute
      pancreatitis (AP). AP was induced in male Balb/C mice by 10 consecutive hourly
      intraperitoneal injections of caerulein. In the treatment groups, CP-96,345 was
      administered at 2.5 mg/kg ip either 30 min before or 1 h after the first
      caerulein injection. Animals were killed, and the lungs and pancreas were
      isolated for RNA extraction and RT-PCR or for immunohistochemical staining. mRNA
      expression of the four adhesion molecules was upregulated in the pancreas during
      AP. Treatment with CP-96,345 effectively reduced the mRNA expression of P
      selectin and E-selectin but not ICAM-1 and VCAM-1. In the lung, ICAM-1, E
      selectin, and P-selectin mRNA expression increased during AP. Antagonist
      treatment suppressed this elevation. Similar expression patterns were seen in the
      immunohistochemical stainings. Intravital microscopy of the pancreatic
      microcirculation revealed the effect of CP-96,345 on leukocyte recruitment. The
      present study provides important information on the relationship between NK1R
      activation and the regulation of adhesion molecules. Also, this study points to
      the differential regulation of inflammation in the pancreas and lung with AP.

PMID- 17218476
TI  - Osmotic regulation of betaine homocysteine-S-methyltransferase expression in
      H4IIE rat hepatoma cells.
AB  - Cell hydration changes critically affect liver metabolism and gene expression. In
      the course of gene expression studies using nylon cDNA-arrays we found that
      hyperosmolarity (405 mosmol/l) suppressed the betaine-homocysteine
      methyltransferase (Bhmt) mRNA expression in H4IIE rat hepatoma cells. This was
      confirmed by Northern blot and real-time quantitative RT-PCR analysis, which in
      addition unraveled a pronounced induction of Bhmt mRNA expression by hypoosmotic
      (205 mosmol/l) swelling. Osmotic regulation of Bhmt mRNA expression was largely
      paralleled at the levels of Bhmt protein and enzymatic activity. Like
      hyperosmotic NaCl, hyperosmotic raffinose but not hyperosmotic urea suppressed
      Bhmt mRNA expression, suggesting that cell shrinkage rather than increased ionic
      strength or hyperosmolarity per se is the trigger. Hypoosmolarity increased the
      expression of a reporter gene driven by the entire human BHMT promoter, whereas
      destabilization of BHMT mRNA was observed under hyperosmotic conditions.
      Osmosensitivity of Bhmt mRNA expression was impaired by inhibitors of tyrosine
      kinases and cyclic nucleotide-dependent kinases. The osmotic regulation of BHMT
      may be part of a cell volume-regulatory response and additionally lead to
      metabolic alterations that depend on the availability of betaine-derived methyl
      groups.

PMID- 17218477
TI  - Unilateral amygdala lesions hamper attentional orienting triggered by gaze
      direction.
AB  - The newly discovered deficit in a bilateral amygdala-damaged case, of not being
      able to allocate attention to the critical feature of a face (Adolphs R, Gosselin
      F, Buchanan TW, Tranel D, Schyns P, Damasio AR. 2005. A mechanism for impaired
      fear recognition after amygdala damage. Nature. 433:68--72.), has opened a new
      window into the function of the amygdala. This case implies that the amygdala
      might be essential in detecting potentially relevant social stimuli, and
      directing attention accordingly. In this study, we have sought to test this
      implication by investigating the behavioral performance of 5 unilateral amygdala
      damaged subjects on spatial cueing tasks. The tasks employed central gaze and
      arrow direction as cues to trigger attentional orienting in peripheral target
      detection. Although age-matched normal controls demonstrated a significant
      congruency effect such that targets presented congruently to cue direction
      elicited faster detection, amygdala subjects demonstrated no such congruency
      effect for gaze cues in the face of a significant congruency effect for arrow
      cues. The results suggest that the social valence of a stimulus is critical for
      amygdala involvement in visual processing. The results also support the
      implicated role of the amygdala in detecting and analyzing relevant social
      stimuli, and orienting attention accordingly.

PMID- 17218478
TI  - Cognitive coping style modulates neural responses to emotional faces in healthy
      humans: a 3-T FMRI study.
AB  - Repression designates coping strategies that aim to shield the organism from
      distressing stimuli by disregarding their aversive characteristics. In contrast,
      sensitization comprises coping strategies that are employed to reduce situational
      uncertainty such as analyzing the environment. Functional magnetic resonance
      imaging was used to study neural correlates of coping styles during the
      perception of threatening and nonthreatening socially relevant information.
      Pictures of human faces bearing fearful (ambiguously threatening), angry
      (unambiguously threatening), happy (nonthreatening), and neutral expressions were
      presented masked and unmasked. Two groups of subjects were examined who were
      defined as consistent repressors versus consistent sensitizers with the Mainz
      Coping Inventory. Sensitizers tended to exhibit stronger neural responses in the
      amygdala to unmasked fearful faces compared with repressors. Overall, repressors
      were cortically more responsive to fearful (ambiguously threatening) and happy
      (nonthreatening) facial expressions than sensitizers, whereas sensitizers
      presented an enhanced responsivity to angry faces in several prefrontal areas,
      that is, unambiguously threatening expressions. Results from time series analyses
      suggest that sensitizers could exhibit less top-down cortical regulation of the
      amygdala than repressors in the processing of fearful faces. An increased
      responsivity of the amygdala to ambiguously threatening stimuli may represent a
      biological determinant of sensitizers' feelings of uncertainty.

PMID- 17218479
TI  - The interaction of brain regions during visual search processing as revealed by
      transcranial magnetic stimulation.
AB  - Although it has long been known that right posterior parietal cortex (PPC) has a
      role in certain visual search tasks, and human motion area V5 is involved in
      processing tasks requiring attention to motion, little is known about how these
      areas may interact during the processing of a task requiring the speciality of
      each. Using transcranial magnetic stimulation (TMS), this study first established
      the specialization of each area in the form of a double dissociation; TMS to
      right PPC disrupted processing of a color/form conjunction and TMS to V5
      disrupted processing of a motion/form conjunction. The key finding of this study
      is, however, if TMS is used to disrupt processing of V5 at its critical time of
      activation during the motion/form conjunction task, concurrent disruption of
      right PPC now has a significant effect, where TMS at PPC alone does not. Our
      findings challenge the conventional interpretation of the role of right PPC in
      conjunction search and spatial attention.

PMID- 17218480
TI  - Excess of neurons in the human newborn mediodorsal thalamus compared with that of
      the adult.
AB  - The aim of this study was to quantify the total number of neurons and glial cells
      in the mediodorsal nucleus of the thalamus (MD) of 8 newborn human brains, in
      comparison to 8 adult human brains. The estimates of the cell numbers were
      obtained using the stereological principles of the optical fractionator. In the
      case of the adults, the total number of neurons in the entire MD was an average
      of 41% lower than in the newborn, which was statistically highly significant (P <
      0.001). The estimated average total number of neurons in MD thalamus of the
      newborns was 11.2 million (coefficient of variation [CV] = standard
      deviation/mean = 0.16), compared with the adults' 6.43 million (CV = 0.15). The
      glial cell numbers were substantially higher in the adult brains, with an
      increase of almost 4 times from 10.6 million at birth to 36.3 million in the
      fully developed adult brain. This is the first demonstration of a higher number
      of human neurons in the brain of newborns compared with the adult.

PMID- 17218481
TI  - Disruption of neuronal migration by RNAi of Dyx1c1 results in neocortical and
      hippocampal malformations.
AB  - The brains of individuals with developmental dyslexia have neocortical neuronal
      migration abnormalities including molecular layer heterotopias, laminar
      dysplasias, and periventricular nodular heterotopias (PNH). RNA interference
      (RNAi) of Dyx1c1, a candidate dyslexia susceptibility gene, disrupts neuronal
      migration in developing embryonic neocortex. Using in utero electroporation, we
      cotransfected cells in the rat neocortical ventricular zone (VZ) at E14/15 with
      short hairpin RNA vectors targeting Dyx1c1 along with either plasmids encoding
      enhanced green fluorescent protein or plasmids encoding monomeric red fluorescent
      protein only. RNAi of Dyx1c1 resulted in pockets of unmigrated neurons resembling
      PNH. The pattern of migration of transfected neurons was bimodal, with
      approximately 20% of the neurons migrating a short distance from the VZ and
      another 40% that migrated past their expected lamina. Approximately 25% of the
      transfected brains had hippocampal pyramidal cell migration anomalies. Molecular
      layer ectopias, which were not related to injection site artifacts, were also
      seen in 25% of the animals. These results support the hypothesis that targeted
      disruption of the candidate dyslexia susceptibility gene, Dyx1c1, results in
      neuronal migration disorders similar to those seen in the brains of dyslexics.

PMID- 17218483
TI  - Structural imaging reveals anatomical alterations in inferotemporal cortex in
      congenital prosopagnosia.
AB  - Congenital prosopagnosia (CP) refers to the lifelong impairment in face
      recognition in individuals who have intact low-level visual processing, normal
      cognitive abilities, and no known neurological disorder. Although the face
      recognition impairment is profound and debilitating, its neural basis remains
      elusive. To investigate this, we conducted detailed morphometric and volumetric
      analyses of the occipitotemporal (OT) cortex in a group of CP individuals and
      matched control subjects using high-spatial resolution magnetic resonance
      imaging. Although there were no significant group differences in the depth or
      deviation from the midline of the OT or collateral sulci, the CP individuals
      evince a larger anterior and posterior middle temporal gyrus and a significantly
      smaller anterior fusiform (aF) gyrus. Interestingly, this volumetric reduction in
      the aF gyrus is correlated with the behavioral decrement in face recognition.
      These findings implicate a specific cortical structure as the neural basis of CP
      and, in light of the familial history of CP, target the aF gyrus as a potential
      site for further, focused genetic investigation.

PMID- 17218482
TI  - Hearing lips and seeing voices: how cortical areas supporting speech production
      mediate audiovisual speech perception.
AB  - Observing a speaker's mouth profoundly influences speech perception. For example,
      listeners perceive an "illusory" "ta" when the video of a face producing /ka/ is
      dubbed onto an audio /pa/. Here, we show how cortical areas supporting speech
      production mediate this illusory percept and audiovisual (AV) speech perception
      more generally. Specifically, cortical activity during AV speech perception
      occurs in many of the same areas that are active during speech production. We
      find that different perceptions of the same syllable and the perception of
      different syllables are associated with different distributions of activity in
      frontal motor areas involved in speech production. Activity patterns in these
      frontal motor areas resulting from the illusory "ta" percept are more similar to
      the activity patterns evoked by AV(/ta/) than they are to patterns evoked by
      AV(/pa/) or AV(/ka/). In contrast to the activity in frontal motor areas,
      stimulus-evoked activity for the illusory "ta" in auditory and somatosensory
      areas and visual areas initially resembles activity evoked by AV(/pa/) and
      AV(/ka/), respectively. Ultimately, though, activity in these regions comes to
      resemble activity evoked by AV(/ta/). Together, these results suggest that AV
      speech elicits in the listener a motor plan for the production of the phoneme
      that the speaker might have been attempting to produce, and that feedback in the
      form of efference copy from the motor system ultimately influences the phonetic
      interpretation.

PMID- 17218484
TI  - A mouse model with liver-specific deletion and global suppression of the NADPH
      cytochrome P450 reductase gene: characterization and utility for in vivo studies
      of cyclophosphamide disposition.
AB  - A mouse model combining liver-specific deletion with global suppression of the
      NADPH-cytochrome P450 reductase gene (Cpr) has been developed and characterized.
      These mice (designated "Cpr-low and liver-Cpr-null" or CL-LCN) retain the
      respective phenotypes of the previously reported Cpr-low (CL) and liver-Cpr-null
      (LCN) mouse strains, but hepatic deletion of the Cpr gene occurs at an earlier
      age in the CL-LCN mouse than in the LCN mouse. Residual hepatic microsomal CPR
      activities are very low in both CL-LCN and LCN mice (at 1.5 and 2.5% of wild-type
      levels, respectively). The utility of CL-LCN mice for in vivo drug metabolism
      studies was explored using the cytochrome P450 (P450) prodrug cyclophosphamide
      (CPA). After i.p. injection of CPA at 100 mg/kg, the t1/2 and the area under the
      concentration-time curve for plasma CPA were significantly increased in mice
      deficient in liver CPR compared with wild-type controls, indicating a lower rate
      of metabolism, with the effects greater in CL-LCN mice than in LCN mice.
      Correspondingly, substantial decreases in Cmax, and increases in Tmax, and t1/2,
      of 4-hydroxycyclophosphamide (4-OH-CPA) formation were observed in both LCN and
      CL-LCN mice relative to wild-type controls. In contrast, CPA and 4-OH-CPA
      pharmacokinetic parameters were essentially unchanged in CL mice, relative to
      wild-type controls. The slower elimination of CPA in CL-LCN mice compared with
      LCN mice suggests a role for extrahepatic P450 in the in vivo metabolism of CPA
      and demonstrates the utility of the CL-LCN model in determining the role of
      extrahepatic P450 enzymes in drug metabolism and chemical toxicity.

PMID- 17218485
TI  - A metabolic screening study of trichostatin A (TSA) and TSA-like histone
      deacetylase inhibitors in rat and human primary hepatocyte cultures.
AB  - Hydroxamic acid (HA)-based histone deacetylase (HDAC) inhibitors, with
      trichostatin A (TSA) as the reference compound, are potential antitumoral drugs
      and show promise in the creation of long-term primary cell cultures. However,
      their metabolic properties have barely been investigated. TSA is rapidly
      inactivated in rodents both in vitro and in vivo. We previously found that 5-(4
      dimethylaminobenzoyl)aminovaleric acid hydroxyamide or 4-Me2N-BAVAH (compound 1)
      is metabolically more stable upon incubation with rat hepatocyte suspensions. In
      this study, we show that human hepatocytes also metabolize TSA more rapidly than
      compound 1 and that similar pathways are involved. Furthermore, structural
      analogs of compound 1 (compounds 2-9) are reported to have the same favorable
      metabolic properties. Removal of the dimethylamino substituent of compound 1
      creates a very stable but 50% less potent inhibitor. Chain lengthening (4 to 5
      carbon spacer) slightly improves both potency and metabolic stability, favoring
      HA reduction to hydrolysis. On the other hand, Calpha-unsaturation and spacer
      methylation not only reduce HDAC inhibition but also increase the rate of
      metabolic inactivation approximately 2-fold, mainly through HA reduction.
      However, in rat hepatocyte monolayer cultures, compound 1 is shown to be
      extensively metabolized by phase II conjugation. In conclusion, this study
      suggests that simple structural modifications of amide-linked TSA analogs can
      improve their phase I metabolic stability in both rat and human hepatocyte
      suspensions. Phase II glucuronidation, however, can compensate for their lower
      phase I metabolism in rat hepatocyte monolayers and could play a yet unidentified
      role in the determination of their in vivo clearance.

PMID- 17218486
TI  - Trace amine-associated receptor 1 displays species-dependent stereoselectivity
      for isomers of methamphetamine, amphetamine, and para-hydroxyamphetamine.
AB  - The synthetic amines methamphetamine (METH), amphetamine (AMPH), and their
      metabolite para-hydroxyamphetamine (POHA) are chemically and structurally related
      to the catecholamine neurotransmitters and a small group of endogenous biogenic
      amines collectively referred to as the trace amines (TAs). Recently, it was
      reported that METH, AMPH, POHA, and the TAs para-tyramine (TYR) and beta
      phenylethylamine (PEA) stimulate cAMP production in human embryonic kidney (HEK)
      293 cells expressing rat trace amine-associated receptor 1 (rTAAR1). The
      discovery that METH and AMPH activate the rTAAR1 motivated us to study the effect
      of these drugs on the mouse TAAR1 (mTAAR1) and a human-rat chimera (hrChTAAR1).
      Furthermore, because S-(+)-isomers of METH and AMPH are reported to be more
      potent and efficacious in vivo than R-(-), we determined the enantiomeric
      selectivity of all three species of TAAR1. In response to METH, AMPH, or POHA
      exposure, the accumulation of cAMP by HEK-293 cells stably expressing different
      species of TAAR1 was concentration- and isomer-dependent. EC50 values for S-(+)
      METH were 0.89, 0.92, and 4.44 microM for rTAAR1, mTAAR1, and h-rChTAAR1,
      respectively. PEA was a potent and full agonist at each species of TAAR1, whereas
      TYR was a full agonist for the rodent TAAR1s but was a partial agonist at h
      rChTAAR1. Interestingly, both isomers of METH were full agonists at mTAAR1 and h
      rChTAAR1, whereas both were partial agonists at rTAAR1. Taken together, these in
      vitro results suggest that, in vivo, TAAR1 could be a novel mediator of the
      effects of these drugs.

PMID- 17218487
TI  - Effects of the protein kinase inhibitor, imatinib mesylate, on
      epithelial/mesenchymal phenotypes: implications for treatment of fibrotic
      diseases.
AB  - Tissue injury in mammals triggers both inflammatory and repair responses that, in
      some contexts, results in fibrosis. Fibrosis is characterized by the persistence
      of activated myofibroblasts, ineffective re-epithelialization, and variable
      degrees of inflammation within injured tissues. The protein kinase inhibitor
      (PKI), imatinib mesylate, has been proposed as a potential antifibrotic
      therapeutic agent. In this study, the efficacy of imatinib mesylate to modulate
      fibrogenic responses, both in vitro and in vivo, was examined. In an in vitro
      fibroblast culture model, imatinib inhibits platelet-derived growth factor
      receptor activation and fibroblast proliferation but not the stably
      differentiated myofibroblast phenotype. Furthermore, imatinib inhibits lung
      epithelial cell proliferation and survival but not the induction of epithelial
      mesenchymal transition. Imatinib does not alter transforming growth factor
      beta/SMAD3 signaling in either cell type. In a murine model of lung fibrosis,
      bleomycin-induced injury to the pulmonary epithelium provokes an early
      inflammatory response with more delayed fibrosis during the late reparative phase
      of lung injury. Imatinib mesylate (10 mg/kg/day by i.p. injection or oral
      gavage), administered during the postinjury repair phase, failed to significantly
      alter fibrogenic responses assessed by histopathology, collagen content, and the
      accumulation of myofibroblasts within the injured lung. These studies indicate
      that the capacity of a PKI to inhibit fibroblast proliferation may be
      insufficient to mediate significant antifibrotic effects in late stages of tissue
      injury repair. Pharmacologic agents that modulate the activities and fate of
      differentiated (myo)fibroblasts, without interfering with the regenerative
      capacity of epithelial cells, are likely to be more effective for treatment of
      nonresolving, progressive fibrotic disorders.

PMID- 17218489
TI  - Role of radiation therapy in the treatment of stage I/II mucosa-associated
      lymphoid tissue lymphoma.
AB  - BACKGROUND: Few large studies exist on the outcome of patients treated for stage
      I/II mucosa-associated lymphoid tissue (MALT) lymphoma. PATIENTS AND METHODS: We
      retrospectively reviewed the records of 77 patients consecutively treated for
      stage I (n = 66) or II (n = 11) MALT lymphoma at our institution. Progression
      free survival (PFS), freedom from treatment failure (FFTF), and overall survival
      (OS) were calculated using the Kaplan-Meier method. RESULTS: The median follow-up
      time was 61 months (range 2-177 months). Fifty-two patients (68%) received local
      radiation therapy (RT) alone, 17 (22%) had surgery followed by adjuvant RT, five
      (6%) had surgery alone, two (3%) had surgery and chemotherapy, and one patient
      had chemotherapy alone. The median RT dose was 30 Gy (range 18-40 Gy). The 5-year
      PFS, FFTF, and OS rates were 76%, 78%, and 91%, respectively. The 5-year PFS (79%
      versus 50%; P = 0.002) and FFTF (81% versus 50%; P = 0.0004) rates were higher
      for patients who received RT as compared with patients who did not. CONCLUSIONS:
      The prognosis following treatment of stage I/II MALT lymphoma is excellent. RT
      improves PFS and FFTF and has an important role in the curative treatment of
      patients with localized disease.

PMID- 17218488
TI  - A phase IB, open-label dose-escalating study of the oral angiogenesis inhibitor
      PTK787/ZK 222584 (PTK/ZK), in combination with FOLFOX4 chemotherapy in patients
      with advanced colorectal cancer.
AB  - BACKGROUND: This open-label, phase IB study was undertaken to determine the
      safety/toxicity profile and recommended dose of oral once-daily PTK787/ZK 222584
      (PTK/ZK) combined with oxaliplatin/5-fluorouracil (5-FU)/leucovorin (FOLFOX4)
      chemotherapy in patients with advanced colorectal cancer. Secondary objectives
      were to assess full pharmacokinetics and gather preliminary evidence of antitumor
      activity. PATIENTS AND METHODS: Thirty-five patients received escalating doses of
      PTK/ZK (range 500-2000 mg daily) continuously. Concurrent FOLFOX4 chemotherapy
      was administered on days 1 and 2 and repeated every 14 days. Dose escalation of
      PTK/ZK was continued until maximum tolerated dose (MTD) was established and
      additional patients were then enrolled at MTD dosage. RESULTS: Mean treatment
      duration of PTK/ZK was 9.5 months. The MTD was 1250 mg daily with dizziness being
      the most frequent dose-limiting toxicity (DLT). Hypertension (23%, grade 3) and
      neutropenia (37%, grades 3 + 4) were the most frequent grade 3 or 4 adverse
      events. Pharmacokinetic analyses found no evidence for interactions between
      PTK/ZK and the combination of 5-FU, leucovorin, and oxaliplatin during
      concomitant use. Median progression-free survival was 11.4 months. CONCLUSION:
      The MTD of PTK/ZK in combination with FOLFOX4 in this patient population is 1250
      mg daily. The combination is feasible and safe and is not associated with
      significant pharmacokinetic interactions.

PMID- 17218491
TI  - Clustering by passing messages between data points.
AB  - Clustering data by identifying a subset of representative examples is important
      for processing sensory signals and detecting patterns in data. Such "exemplars"
      can be found by randomly choosing an initial subset of data points and then
      iteratively refining it, but this works well only if that initial choice is close
      to a good solution. We devised a method called "affinity propagation," which
      takes as input measures of similarity between pairs of data points. Real-valued
      messages are exchanged between data points until a high-quality set of exemplars
      and corresponding clusters gradually emerges. We used affinity propagation to
      cluster images of faces, detect genes in microarray data, identify representative
      sentences in this manuscript, and identify cities that are efficiently accessed
      by airline travel. Affinity propagation found clusters with much lower error than
      other methods, and it did so in less than one-hundredth the amount of time.

PMID- 17218490
TI  - Influence of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone
      on serologic parameters and clinical course in lymphoma patients with autoimmune
      diseases.
AB  - BACKGROUND: As patients with B-cell lymphomas suffering from an underlying
      autoimmune condition undergoing therapy with the CD20 antibody rituximab,
      cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) offer the
      unique possibility of monitoring effects of therapy on various rheumatologic
      parameters, we have evaluated serologic autoimmune markers and the clinical
      outcome of patients with autoimmune diseases (ADs) who received lymphoma
      treatment with R-CHOP during the course of their disease. PATIENTS AND METHODS:
      We have retrospectively analysed 13 patients with non-Hodgkin's lymphoma who
      concurrently suffered from ADs and were treated with the R-CHOP regimen.
      Subjective parameters along with rheumatoid factor (RF) and antinuclear
      antibodies (ANA) were serially measured. RESULTS: The median levels of RF were
      901 IU/ml [inter-quartile-range (IQR) 189-2520] before and 75 IU/ml (IQR 45-644)
      after therapy (P = 0.028). The median levels of ANA were 800 (IQR 140-2560)
      before and 100 (40-1280) after therapy (P = 0.027). Ten (77%) patients showed
      clinical improvement of their autoimmune symptoms, two (15%) reported no
      difference and one (7%) patient with rheumatoid arthritis-related worsening
      symptoms during therapy with R-CHOP. The autoimmune-related symptoms recurred
      after a median time of 7 weeks (IQR 6-8) in seven patients. In terms of lymphoma
      response, 11 patients achieved a complete remission and two a partial remission.
      CONCLUSIONS: This analysis indicates that R-CHOP given for lymphoma treatment is
      also effective for therapy of concurrent rheumatoid diseases. Both rheumatoid
      parameters as well as clinical symptoms showed a significant decrease during
      treatment with this immunochemotherapy. The effects on the rheumatic diseases,
      however, seem to be of limited duration.

PMID- 17218492
TI  - Ex situ NMR in highly homogeneous fields: 1H spectroscopy.
AB  - Portable single-sided nuclear magnetic resonance (NMR) magnets used for
      nondestructive studies of large samples are believed to generate inherently
      inhomogeneous magnetic fields. We demonstrated experimentally that the field of
      an open magnet can be shimmed to high homogeneity in a large volume external to
      the sensor. This technique allowed us to measure localized high-resolution proton
      spectra outside a portable open magnet with a spectral resolution of 0.25 part
      per million. The generation of these experimental conditions also simplifies the
      implementation of such powerful methodologies as multidimensional NMR
      spectroscopy and imaging.

PMID- 17218493
TI  - Floral gigantism in Rafflesiaceae.
AB  - Species of Rafflesiaceae possess the world's largest flowers (up to 1 meter in
      diameter), yet their precise evolutionary relationships have been elusive,
      hindering our understanding of the evolution of their extraordinary reproductive
      morphology. We present results of phylogenetic analyses of mitochondrial,
      nuclear, and plastid data showing that Rafflesiaceae are derived from within
      Euphorbiaceae, the spurge family. Most euphorbs produce minute flowers,
      suggesting that the enormous flowers of Rafflesiaceae evolved from ancestors with
      tiny flowers. Given the inferred phylogeny, we estimate that there was a circa 79
      fold increase in flower diameter on the stem lineage of Rafflesiaceae, making
      this one of the most dramatic cases of size evolution reported for eukaryotes.

PMID- 17218494
TI  - Improved oxygen reduction activity on Pt3Ni(111) via increased surface site
      availability.
AB  - The slow rate of the oxygen reduction reaction (ORR) in the polymer electrolyte
      membrane fuel cell (PEMFC) is the main limitation for automotive applications. We
      demonstrated that the Pt3Ni(111) surface is 10-fold more active for the ORR than
      the corresponding Pt(111) surface and 90-fold more active than the current state
      of-the-art Pt/C catalysts for PEMFC. The Pt3Ni(111) surface has an unusual
      electronic structure (d-band center position) and arrangement of surface atoms in
      the near-surface region. Under operating conditions relevant to fuel cells, its
      near-surface layer exhibits a highly structured compositional oscillation in the
      outermost and third layers, which are Pt-rich, and in the second atomic layer,
      which is Ni-rich. The weak interaction between the Pt surface atoms and
      nonreactive oxygenated species increases the number of active sites for O2
      adsorption.

PMID- 17218495
TI  - Outreach training needed.

PMID- 17218496
TI  - Stem cells. Versatile stem cells without the ethical baggage?

PMID- 17218498
TI  - U.S. national security. Head of weapons program fired.

PMID- 17218497
TI  - Energy. Consortium wins big drilling technology contract.

PMID- 17218499
TI  - Chemistry. Platinum in fuel cells gets a helping hand.

PMID- 17218501
TI  - Nuclear waste. With plutonium, even ceramics may slump.

PMID- 17218500
TI  - Human genetics. In Asians and whites, gene expression varies by race.

PMID- 17218502
TI  - Ocean policy. Panel urges environmental controls on offshore aquaculture.

PMID- 17218503
TI  - Epidemiology. Agent Orange's bitter harvest.

PMID- 17218504
TI  - Neurobiology. Fruit fly fight club.

PMID- 17218505
TI  - AGBIOTECH. GM technology develops in the developing world.

PMID- 17218506
TI  - PTSD and Vietnam Veterans.

PMID- 17218507
TI  - Disbelievers in evolution.

PMID- 17218508
TI  - Comment on "A common genetic variant is associated with adult and childhood
      obesity".
AB  - Herbert et al. (Reports, 14 April 2006, p. 279) reported an association between
      the INSIG2 gene variant rs7566605 and obesity in four sample populations, under a
      recessive model. We attempted to replicate this result in 10,265 Caucasian
      individuals, combining family-based, case-control, and general population
      studies, but found no support for a major role of this variant in obesity.

PMID- 17218509
TI  - Comment on "A common genetic variant is associated with adult and childhood
      obesity".
AB  - Herbert et al. (Reports, 14 April 2006, p. 279) found that the rs7566605 genetic
      variant, located upstream of the INSIG2 gene, was consistently associated with
      increased body mass index. However, we found no evidence of association between
      rs7566605 and body mass index in two large ethnically homogeneous population
      based cohorts. On the contrary, an opposite tendency was observed.

PMID- 17218510
TI  - Comment on "A common genetic variant is associated with adult and childhood
      obesity".
AB  - Contrary to the findings of Herbert et al. (Reports, 14 April 2006, p. 279),
      homozygous carriers of the C allele of the rs7566605 variant near the INSIG2 gene
      did not exhibit a significantly increased risk for obesity in a large population
      based cross-sectional German study. A subgroup analysis, however, revealed that
      this allele significantly increased the risk for obesity in already overweight
      individuals.

PMID- 17218511
TI  - Science and law. The obvious war.

PMID- 17218512
TI  - Ecology. Dipping into the rare biosphere.

PMID- 17218513
TI  - Astronomy. A supernova riddle.

PMID- 17218514
TI  - Anthropology. The missing years for modern humans.

PMID- 17218515
TI  - Physics. Electron nematic phase in a transition metal oxide.

PMID- 17218516
TI  - Microbiology. A proteomic snapshot of life at a vent.

PMID- 17218517
TI  - Molecular biology. Amplified silencing.

PMID- 17218518
TI  - Proteasome-independent functions of ubiquitin in endocytosis and signaling.
AB  - Ubiquitination is a reversible posttranslational modification of cellular
      proteins, in which a 76-amino acid polypeptide, ubiquitin, is primarily attached
      to the epsilon-amino group of lysines in target proteins. Ubiquitination is a
      major player in regulating a broad host of cellular processes, including cell
      division, differentiation, signal transduction, protein trafficking, and quality
      control. Aberrations in the ubiquitination system are implicated in pathogenesis
      of some diseases, certain malignancies, neurodegenerative disorders, and
      pathologies of the inflammatory immune response. Here, we discuss the proteasome
      independent roles of ubiquitination in signaling and endocytosis.

PMID- 17218519
TI  - Haploid females in the parasitic wasp Nasonia vitripennis.
AB  - The insect order of Hymenoptera (ants, bees, sawflies, and wasps) consists almost
      entirely of haplodiploid species. Under haplodiploidy, males develop from
      unfertilized eggs and are haploid, whereas females develop from fertilized eggs
      and are diploid. Although diploid males commonly occur, haploid females have
      never been reported. In analyzing the phenomenon of gynandromorphism in the
      parasitoid wasp Nasonia vitripennis, we found a line that generates complete
      phenotypic females from unfertilized eggs. These females have ovaries, can lay
      eggs, and are haploid, as shown by cytological and flow cytometric analyses. The
      data show that diploidy is not necessary for female development.

PMID- 17218521
TI  - Highly siderophile element constraints on accretion and differentiation of the
      Earth-Moon system.
AB  - A new combined rhenium-osmium- and platinum-group element data set for basalts
      from the Moon establishes that the basalts have uniformly low abundances of
      highly siderophile elements. The data set indicates a lunar mantle with long
      term, chondritic, highly siderophile element ratios, but with absolute abundances
      that are over 20 times lower than those in Earth's mantle. The results are
      consistent with silicate-metal equilibrium during a giant impact and core
      formation in both bodies, followed by post-core-formation late accretion that
      replenished their mantles with highly siderophile elements. The lunar mantle
      experienced late accretion that was similar in composition to that of Earth but
      volumetrically less than (approximately 0.02% lunar mass) and terminated earlier
      than for Earth.

PMID- 17218522
TI  - Stabilization of platinum oxygen-reduction electrocatalysts using gold clusters.
AB  - We demonstrated that platinum (Pt) oxygen-reduction fuel-cell electrocatalysts
      can be stabilized against dissolution under potential cycling regimes (a
      continuing problem in vehicle applications) by modifying Pt nanoparticles with
      gold (Au) clusters. This behavior was observed under the oxidizing conditions of
      the O2 reduction reaction and potential cycling between 0.6 and 1.1 volts in over
      30,000 cycles. There were insignificant changes in the activity and surface area
      of Au-modified Pt over the course of cycling, in contrast to sizable losses
      observed with the pure Pt catalyst under the same conditions. In situ x-ray
      absorption near-edge spectroscopy and voltammetry data suggest that the Au
      clusters confer stability by raising the Pt oxidation potential.

PMID- 17218520
TI  - Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis.
AB  - We describe the genome sequence of the protist Trichomonas vaginalis, a sexually
      transmitted human pathogen. Repeats and transposable elements comprise about two
      thirds of the approximately 160-megabase genome, reflecting a recent massive
      expansion of genetic material. This expansion, in conjunction with the shaping of
      metabolic pathways that likely transpired through lateral gene transfer from
      bacteria, and amplification of specific gene families implicated in pathogenesis
      and phagocytosis of host proteins may exemplify adaptations of the parasite
      during its transition to a urogenital environment. The genome sequence predicts
      previously unknown functions for the hydrogenosome, which support a common
      evolutionary origin of this unusual organelle with mitochondria.

PMID- 17218523
TI  - Early Upper Paleolithic in Eastern Europe and implications for the dispersal of
      modern humans.
AB  - Radiocarbon and optically stimulated luminescence dating and magnetic
      stratigraphy indicate Upper Paleolithic occupation-probably representing modern
      humans-at archaeological sites on the Don River in Russia 45,000 to 42,000 years
      ago. The oldest levels at Kostenki underlie a volcanic ash horizon identified as
      the Campanian Ignimbrite Y5 tephra that is dated elsewhere to about 40,000 years
      ago. The occupation layers contain bone and ivory artifacts, including possible
      figurative art, and fossil shells imported more than 500 kilometers. Thus, modern
      humans appeared on the central plain of Eastern Europe as early as anywhere else
      in northern Eurasia.

PMID- 17218524
TI  - Late Pleistocene human skull from Hofmeyr, South Africa, and modern human
      origins.
AB  - The lack of Late Pleistocene human fossils from sub-Saharan Africa has limited
      paleontological testing of competing models of recent human evolution. We have
      dated a skull from Hofmeyr, South Africa, to 36.2 +/- 3.3 thousand years ago
      through a combination of optically stimulated luminescence and uranium-series
      dating methods. The skull is morphologically modern overall but displays some
      archaic features. Its strongest morphometric affinities are with Upper
      Paleolithic (UP) Eurasians rather than recent, geographically proximate people.
      The Hofmeyr cranium is consistent with the hypothesis that UP Eurasians descended
      from a population that emigrated from sub-Saharan Africa in the Late Pleistocene.

PMID- 17218525
TI  - Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the
      transcription factor SOX13.
AB  - alphabeta and gammadelta T cells originate from a common, multipotential
      precursor population in the thymus, but the molecular mechanisms regulating this
      lineage-fate decision are unknown. We have identified Sox13 as a gammadelta
      specific gene in the immune system. Using Sox13 transgenic mice, we showed that
      this transcription factor promotes gammadelta T cell development while opposing
      alphabeta T cell differentiation. Conversely, mice deficient in Sox13 expression
      exhibited impaired development of gammadelta T cells but not alphabeta T cells.
      One mechanism of SOX13 function is the inhibition of signaling by the
      developmentally important Wnt/T cell factor (TCF) pathway. Our data thus reveal a
      dominant pathway regulating the developmental fate of these two lineages of T
      lymphocytes.

PMID- 17218526
TI  - A systems approach to measuring the binding energy landscapes of transcription
      factors.
AB  - A major goal of systems biology is to predict the function of biological
      networks. Although network topologies have been successfully determined in many
      cases, the quantitative parameters governing these networks generally have not.
      Measuring affinities of molecular interactions in high-throughput format remains
      problematic, especially for transient and low-affinity interactions. We describe
      a high-throughput microfluidic platform that measures such properties on the
      basis of mechanical trapping of molecular interactions. With this platform we
      characterized DNA binding energy landscapes for four eukaryotic transcription
      factors; these landscapes were used to test basic assumptions about transcription
      factor binding and to predict their in vivo function.

PMID- 17218527
TI  - A large-scale deforestation experiment: effects of patch area and isolation on
      Amazon birds.
AB  - As compared with extensive contiguous areas, small isolated habitat patches lack
      many species. Some species disappear after isolation; others are rarely found in
      any small patch, regardless of isolation. We used a 13-year data set of bird
      captures from a large landscape-manipulation experiment in a Brazilian Amazon
      forest to model the extinction-colonization dynamics of 55 species and tested
      basic predictions of island biogeography and metapopulation theory. From our
      models, we derived two metrics of species vulnerability to changes in isolation
      and patch area. We found a strong effect of area and a variable effect of
      isolation on the predicted patch occupancy by birds.

PMID- 17218528
TI  - Physiological proteomics of the uncultured endosymbiont of Riftia pachyptila.
AB  - The bacterial endosymbiont of the deep-sea tube worm Riftia pachyptila has never
      been successfully cultivated outside its host. In the absence of cultivation
      data, we have taken a proteomic approach based on the metagenome sequence to
      study the metabolism of this peculiar microorganism in detail. As one result, we
      found that three major sulfide oxidation proteins constitute approximately 12% of
      the total cytosolic proteome, which highlights the essential role of these
      enzymes for the symbiont's energy metabolism. Unexpectedly, the symbiont uses the
      reductive tricarboxylic acid cycle in addition to the previously identified
      Calvin cycle for CO2 fixation.

PMID- 17218529
TI  - An H-NS-like stealth protein aids horizontal DNA transmission in bacteria.
AB  - The Sfh protein is encoded by self-transmissible plasmids involved in human
      typhoid and is closely related to the global regulator H-NS. We have found that
      Sfh provides a stealth function that allows the plasmids to be transmitted to new
      bacterial hosts with minimal effects on their fitness. Introducing the plasmid
      without the sfh gene imposes a mild H-NS(-) phenotype and a severe loss of
      fitness due to titration of the cellular pool of H-NS by the A+T-rich plasmid.
      This stealth strategy seems to be used widely to aid horizontal DNA transmission
      and has important implications for bacterial evolution.

PMID- 17218532
TI  - The prevalence of stuttering, voice, and speech-sound disorders in primary school
      students in Australia.
AB  - PURPOSE: The aims of this study were threefold: to report teachers' estimates of
      the prevalence of speech disorders (specifically, stuttering, voice, and speech
      sound disorders); to consider correspondence between the prevalence of speech
      disorders and gender, grade level, and socioeconomic status; and to describe the
      level of support provided to schoolchildren with speech disorders. METHOD:
      Students with speech disorders were identified from 10,425 students in Australia
      using a 4-stage process: training in the data collection process, teacher
      identification, confirmation by a speech-language pathologist, and consultation
      with district special needs advisors. RESULTS: The prevalence of students with
      speech disorders was estimated; specifically, 0.33% of students were identified
      as stuttering, 0.12% as having a voice disorder, and 1.06% as having a speech
      sound disorder. There was a higher prevalence of speech disorders in males than
      in females. As grade level increased, the prevalence of speech disorders
      decreased. There was no significant difference in the pattern of prevalence
      across the three speech disorders and four socioeconomic groups; however,
      students who were identified with a speech disorder were more likely to be in the
      higher socioeconomic groups. Finally, there was a difference between the
      perceived and actual level of support that was provided to these students.
      CONCLUSION: These prevalence figures are lower than those using initial
      identification by speech-language pathologists and similar to those using parent
      report.

PMID- 17218530
TI  - Picobiliphytes: a marine picoplanktonic algal group with unknown affinities to
      other eukaryotes.
AB  - Environmental sequencing has revealed unimagined diversity among eukaryotic
      picoplankton. A distinct picoplanktonic algal group, initially detected from 18S
      ribosomal DNA (rDNA) sequences, was hybridized with rRNA-targeted probes,
      detected by tyramide signal amplification-fluorescent in situ hybridization, and
      showed an organelle-like body with orange fluorescence indicative of phycobilins.
      Using this fluorescence signal, cells were sorted by flow cytometry and probed.
      Hybridized cells contained a 4',6'-diamidino-2-phenylindole-stained organelle
      resembling a plastid with a nucleomorph. This suggests that they may be secondary
      endosymbiotic algae. Pending the isolation of living cells and their formal
      description, these algae have been termed picobiliphytes.

PMID- 17218533
TI  - Increasing print awareness in preschoolers with language impairment using non
      evocative print referencing.
AB  - PURPOSE: This study examined the extent to which using non-evocative, explicit
      referencing of print concepts during shared storybook reading in the context of
      language therapy facilitated print concept knowledge in children with language
      impairment. METHOD: Five children, ages 4 to 5 years, were provided scripted
      input on 20 print concepts during shared storybook reading that was incorporated
      into individualized 30-min language intervention sessions that were conducted in
      the children's classroom twice weekly. The children were not required to make any
      response to the input on print concepts, and the input was secondary to
      instruction in the language targets during the 10-min shared storybook reading
      activity. RESULTS: Using a single-subject, multiple probe design across subjects,
      results indicated that children's knowledge of print concepts improved markedly
      when the procedure was incorporated into shared storybook reading and that they
      continued to learn and maintain knowledge of print concepts with repeated input.
      CLINICAL IMPLICATIONS: These findings suggest that children with language
      impairment may benefit from simple non-evocative, explicit referencing strategies
      that can be easily incorporated into the context of storybook reading during
      language therapy, thus providing speech-language pathologists with an additional
      tool for facilitating children's literacy skills.

PMID- 17218534
TI  - The critical shortage of speech-language pathologists in the public school
      setting: features of the work environment that affect recruitment and retention.
AB  - PURPOSE: The primary focus of this study was to elicit the perspectives of speech
      language pathologists (SLPs) regarding features of the work environment that
      contribute to and/or hinder recruitment and retention in the public school
      setting. METHOD: A questionnaire was distributed to SLPs employed in 10 school
      districts in Central Florida representing small, medium, and large school
      districts. The primary goal of the questionnaire was to elicit the perspectives
      of school-based SLPs regarding (a) factors in the work environment that
      contribute to retention, (b) factors in the work environment that hinder
      retention, and (c) issues that may contribute to the recruitment and retention of
      SLPs in the school setting. A total of 382 questionnaires was obtained, yielding
      a 64.5% response rate. RESULTS: The participants ranked working with children,
      school schedule, and educational setting as primary reasons for their
      satisfaction with working in the public school setting. The participants ranked
      workload, role ambiguity, salary, and caseload as primary reasons for their
      dissatisfaction with working in the public school setting. CONCLUSION: Themes
      emerged from the data that provide insight into several factors that serve as
      powerful influences in understanding issues of recruitment and retention of SLPs
      in the public school setting.

PMID- 17218535
TI  - Speech and articulatory rates of school-age children in conversation and
      narrative contexts.
AB  - PURPOSE: This study provides preliminary reference data for speech and
      articulatory rates of school-age children in conversational and narrative
      speaking contexts. METHOD: Participants included 36 typically developing children
      in 3 groups of 12 participants at ages 7, 9, and 11 years. Conversational and
      narrative speech rates were measured in words per minute, syllables per minute,
      and syllables per second. RESULTS: Speaking rates increased with age between ages
      7 and 9, but rates were similar between ages 9 and 11. Between contexts, only the
      words per minute measure was significantly higher (faster) in narrative than in
      conversation. IMPLICATIONS: These results are important to the assessment,
      treatment, and management of children with communication disorders in clinical or
      school settings.

PMID- 17218536
TI  - Characteristics of speech errors produced by children with and without delayed
      phonological awareness skills.
AB  - PURPOSE: The purpose of this study was to examine the relationship between the
      types of speech errors that are produced by children with speech-sound disorders
      and the children's phonological awareness skills during their prekindergarten and
      kindergarten years. METHOD: Fifty-eight children with speech-sound disorders were
      assessed during the spring of their prekindergarten year and then again at the
      end of their kindergarten year. The children's responses on the Goldman-Fristoe
      Test of Articulation (R. Goldman & M. Fristoe, 2000) were described in terms of
      match ratios for the features of each target sound and the type of error
      produced. Match ratios and error type frequencies were then examined as a
      function of the child's performance on a test of phonological awareness. RESULTS:
      Lower match ratios for +distributed and higher frequencies of typical syllable
      structure errors and atypical segment errors were associated with poorer
      phonological awareness test performance. However, no aspect of the children's
      error patterns proved to be a reliable indicator of which individual child would
      pass or fail the test. The best predictor of test performance at the end of the
      kindergarten year was test performance 1 year earlier. Children who achieved age
      appropriate articulation skills by the end of kindergarten also achieved age
      appropriate phonological awareness skills. CONCLUSION: Children who enter
      kindergarten with delayed articulation skills should be monitored to ensure age
      appropriate acquisition of phonological awareness and literacy skills.

PMID- 17218537
TI  - The effects of in-service education to promote emergent literacy in child care
      centers: a feasibility study.
AB  - PURPOSE: The purpose of this study was to determine the feasibility of a 2-day in
      service education program for (a) promoting the use of two emergent literacy
      strategies by early childhood educators and (b) increasing children's responses
      to these strategies. METHOD: Sixteen early childhood educators were randomly
      assigned to an experimental and a control group. The experimental in-service
      program sought to increase educators' use of abstract utterances and print
      references. Educators were videotaped with small groups of preschoolers during
      storybook reading and a post-story craft activity. Pretest and posttest
      videotapes were coded to yield rates of abstract language, verbal print
      references, and children's responses. RESULTS: In comparison to the control
      group, educators in the experimental program used more abstract utterances that
      elicited talk about emotions and children's past experiences during storybook
      reading. They also used significantly more print references during a post-story
      craft activity. In addition, children in the experimental group responded more
      often with appropriate responses to abstract utterances and print references in
      comparison to children in the control group. CONCLUSION: A 2-day in-service
      education program resulted in short-term behavioral changes in educators' use of
      abstract language and print references. Suggestions for improving instruction
      include providing opportunities for classroom practice with feedback, modeling
      the use of strategies in classroom routines, and long-term mentoring of educators
      to promote retention of gains.

PMID- 17218538
TI  - Oral L-glutamine increases GABA levels in striatal tissue and extracellular
      fluid.
AB  - We explored the possibility that circulating glutamine affects gamma-aminobutyric
      acid (GABA) levels in rat striatal tissue and GABA concentrations in striatal
      extracellular fluid (ECF). Striatal microdialysates, each collected over a 20 min
      interval, were obtained after no treatment, oral L-glutamine (0.5 g/kg), or
      glutamine followed by NMDA (administered via the microdialysis probe). GABA
      concentrations were measured by HPLC using a stable OPA/sulfite precolumn
      derivatization and an electrochemical detection method. L-Glutamine
      administration significantly increased ECF GABA concentrations by 30%, and
      enhanced the response evoked by NMDA alone (70%) to 120% over baseline (all
      P<0.05). Striatal GABA levels increased significantly 2.5 h after oral L
      glutamine (e.g., from 1.76 +/- 0.04 micromol/g in vehicle-treated rats to 2.00 +/
      0.15 micromol/g in those receiving 2.0 g/kg of glutamine). Striatal glutamine
      levels also increased significantly, but not those of glutamate. These data
      suggest that GABA synthesis in, and release from, rat striatum may be regulated
      in part by circulating glutamine. Hence, glutamine administration may provide a
      useful adjunct for treating disorders (e.g., anxiety, seizures) when enhanced
      GABAergic transmission is desired. Moreover, the elevation in plasma and brain
      glutamine associated with hepatic failure may, by increasing brain GABA release,
      produce some of the manifestations of hepatic encephalopathy.

PMID- 17218540
TI  - Efficient gene delivery targeted to the brain using a transferrin-conjugated
      polyethyleneglycol-modified polyamidoamine dendrimer.
AB  - The blood-brain barrier (BBB) poses great difficulties for gene delivery to the
      brain. To circumvent the BBB, we investigated a novel brain-targeting gene vector
      based on the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), in
      vitro and in vivo. Transferrin (Tf) was selected as a brain-targeting ligand
      conjugated to PAMAM via bifunctional polyethyleneglycol (PEG), yielding PAMAM-PEG
      Tf. UV and nuclear magnetic resonance (NMR) spectroscopy were used to evaluate
      the synthesis of vectors. The characteristics and biodistribution of gene vectors
      were evaluated by fluorescent microscopy, flow cytometry, and a radiolabeling
      method. The transfection efficiency of vector/DNA complexes in brain capillary
      endothelial cells (BCECs) was evaluated by fluorescent microscopy and
      determination of luciferase activity. The potency of vector/DNA complexes was
      evaluated by using frozen sections and measuring tissue luciferase activity in
      Balb/c mice after i.v. administration. UV and NMR results demonstrated the
      successful synthesis of PAMAM-PEG-Tf. This vector showed a concentration
      dependent manner in cellular uptake study and a 2.25-fold brain uptake compared
      with PAMAM and PAMAM-PEG in vivo. Transfection efficiency of PAMAM-PEG-Tf/DNA
      complex was much higher than PAMAM/DNA and PAMAM-PEG/DNA complexes in BCECs.
      Results of tissue expression experiments indicated the widespread expression of
      an exogenous gene in mouse brain after i.v. administration. With a PAMAM/DNA
      weight ratio of 10:1, the brain gene expression of the PAMAM-PEG-Tf/DNA complex
      was approximately 2-fold higher than that of the PAMAM/DNA and PAMAM-PEG/DNA
      complexes. These results suggested that PAMAM-PEG-Tf can be exploited as a
      potential nonviral gene vector targeting to brain via noninvasive administration.

PMID- 17218539
TI  - Hypochlorite-modified albumin colocalizes with RAGE in the artery wall and
      promotes MCP-1 expression via the RAGE-Erk1/2 MAP-kinase pathway.
AB  - Signal transduction via the endothelial receptor for advanced glycation end
      products (RAGE) plays a key role in vascular inflammation. Recent observations
      have shown that the myeloperoxidase-H2O2-chloride system of activated phagocytes
      is highly up-regulated under inflammatory conditions where hypochlorous acid
      (HOCl) is formed as the major oxidant. Albumin, an in vivo carrier for
      myeloperoxidase is highly vulnerable to oxidation and a major representative of
      circulating advanced oxidized proteins during inflammatory diseases.
      Immunohistochemical studies performed in the present study revealed marked
      colocalization of HOCl-modified epitopes with RAGE and albumin in sections of
      human atheroma, mainly at the endothelial lining. We show that albumin modified
      with physiologically relevant concentrations of HOCl, added as reagent or
      generated by the myeloperoxidase-H2O2-chloride system, is a high affinity ligand
      for RAGE. Albumin, modified by HOCl in the absence of free amino
      acids/carbohydrates/lipids to exclude formation of AGE-like structures, induced a
      rapid, RAGE-dependent activation of extracellular signal-regulated kinase 1/2 and
      up-regulation of the proinflammatory mediator monocyte chemoattractant protein-1.
      Cellular activation could be blocked either by a specific polyclonal anti-RAGE
      IgG and/or a specific mitogen-activated protein-kinase kinase inhibitor. The
      present study demonstrates that HOCl-modified albumin acts as a ligand for RAGE
      and promotes RAGE-mediated inflammatory complications.

PMID- 17218542
TI  - The relevance of salt bridges for the stability of the influenza virus
      hemagglutinin.
AB  - Hemagglutinin (HA) of influenza virus undergoes an irreversible conformational
      change at acidic pH, mediating viral fusion with the host endosomal membrane. To
      unravel the molecular basis of the pH-dependent stability of HA, we demonstrate
      by mutagenesis of the prototype HA of virus strain X31 (H3 subtype) that salt
      bridges, especially a tetrad salt bridge within the monomers, are crucial for
      folding and stability of the trimeric ectodomain. This complex (tetrad) salt
      bridge is highly conserved among influenza virus subtypes. Introducing additional
      sites of electrostatic attraction between monomers in the distal region enhanced
      the stability of ectodomain at low pH mimicking the natural variant H2 subtype.
      We propose that distinct salt bridges in the distal domain may contribute to the
      enhanced stability of HA of natural virus variants. This hypothesis may provide
      clues to understanding adaptations of virus strains (for example, avian influenza
      viruses) in order to preserve stability of the protein in the host-specific
      environment.

PMID- 17218541
TI  - Formyl peptide receptors and the regulation of ACTH secretion: targets for
      annexin A1, lipoxins, and bacterial peptides.
AB  - The N-formyl peptide receptors (FPRs) are a family of G-protein coupled receptors
      that respond to proinflammatory N-formylated bacterial peptides (e.g., formyl-Met
      Leu-Phe, fMLF) and, thus, contribute to the host response to bacterial infection.
      Paradoxically, a growing body of evidence suggests that some members of this
      receptor family may also be targets for certain anti-inflammatory molecules,
      including annexin A1 (ANXA1), which is an important mediator of glucocorticoid
      (GC) action. To explore further the potential role of FPRs in mediating ANXA1
      actions, we have focused on the pituitary gland, where ANXA1 has a well-defined
      role as a cell-cell mediator of the inhibitory effects of GCs on the secretion of
      corticotrophin (ACTH), and used molecular, genetic, and pharmacological
      approaches to address the question in well-established rodent models. Reverse
      transcriptase-polymerase chain reaction (RT-PCR) analysis identified mRNAs for
      four FPR family members in the mouse anterior pituitary gland, Fpr-rs1, Fpr-rs2,
      Fpr-rs6, and Fpr-rs7. Functional studies confirmed that, like dexamethasone,
      ANXA1 and two ANXA1-derived peptides (ANXA1(1-188) and ANXA1(Ac2-26)) inhibit the
      evoked release of ACTH from rodent anterior pituitary tissue in vitro. Fpr1 gene
      deletion failed to modify the pituitary responses to dexamethasone or ANXA1(Ac2
      26). However, lipoxin A4 (LXA4, 0.02-2 microM, a lipid mediator with high
      affinity for Fpr-rs1) mimicked the inhibitory effects of ANXA1 on ACTH release as
      also did fMLF in high (1-100 microM) but not lower (10-100 nM) concentrations.
      Additionally, a nonselective FPR antagonist (Boc1, 100 microM) overcame the
      effects of dexamethasone, ANXA1(1-188), ANXA1(Ac2-26), fMLF, and LXA4 on ACTH
      release, although at a lower concentration (50 microM), it was without effect.
      Together, the results suggest that the actions of ANXA1 in the pituitary gland
      are independent of Fpr1 but may involve other FPR family members, in particular,
      Fpr-rs1 or a closely related receptor. They thus provide the first evidence for a
      role of the FPR family in the regulation of neuroendocrine function.

PMID- 17218543
TI  - Ammonia secretion from fish gill depends on a set of Rh glycoproteins.
AB  - Ammonia excretion from the gill in teleost fish is essential for nitrogen
      elimination. Although numerous physiological studies have measured ammonia
      excretion, the mechanism of ammonia movement through the membranes of gill
      epithelial cells is still unknown. Mammalian Rh glycoproteins are members of a
      family of proteins that mediate ammonia transport in bacteria, yeast, and plants.
      We identified the Rh glycoprotein homologs, fRhag, fRhbg, fRhcg1, and fRhcg2, of
      the pufferfish, Takifugu rubripes. Northern blot, in situ hybridization, and
      immunohistochemistry revealed that the pufferfish erythroid Rh glycoprotein
      homologue fRhag was present in red blood cells and the hematological organs
      (spleen and kidney) in fish. All four pufferfish Rh glycoproteins are
      specifically localized in the gill and line the pillar cells, pavement cells, and
      the mitochondrion-rich cells. Heterologous expression in Xenopus oocytes showed
      that they mediate methylammonium (an analog of ammonium) transport. These results
      suggest that pufferfish Rh glycoproteins are involved in ammonia excretion from
      the gill. These findings challenge the classic view that ammonia excretion in the
      fish gill occurs by passive diffusion.

PMID- 17218544
TI  - Vacuolar cysteine proteases of wheat (Triticum aestivum L.) are common to leaf
      senescence induced by different factors.
AB  - Cellular proteins are extensively degraded during leaf senescence, and this
      correlates with an up-regulation of protease gene expression, particularly
      cysteine proteases. The objectives of this work were (i) to detect cysteine
      proteases associated with senescence of wheat leaves under different conditions
      and (ii) to find out their subcellular location. Activity labelling of cysteine
      proteases with the biotinylated inhibitor DCG-04 detected five bands at 27, 36,
      39, 42, and 46 kDa in leaves of wheat senescing under continuous darkness. In-gel
      activity assays showed that these proteases are only active in an acid milieu (pH
      4), and their activity increased several-fold in senescing leaves. Fractionation
      experiments showed that the senescence-associated cysteine proteases of 36, 39,
      42, and 46 kDa localize to a vacuolar-enriched fraction. The vacuolar cysteine
      proteases of 36, 39, and 42 kDa increased in activity in attached flag leaves
      senescing naturally during post-anthesis, and in attached leaves of plants
      subjected to a period of water deficit. Thus, the activity of these vacuolar
      cysteine proteases is associated with developmental (post-anthesis) senescence
      and with senescence induced by stress factors (i.e. protracted darkness or
      drought). This suggests that vacuoles are involved in senescence-associated
      cellular degradation, and that different senescence-inducing factors may converge
      on a single degradation pathway.

PMID- 17218546
TI  - Procalcitonin-guided antibiotic therapy in COPD exacerbations: closer but not
      quite there.

PMID- 17218545
TI  - The outermost cuticle of soybean seeds: chemical composition and function during
      imbibition.
AB  - Seeds of different cultivars of Glycine max (L.) Merr. (soybean) have strikingly
      different rates of water imbibition. Seeds that readily imbibe water are termed
      'soft', while those that remain non-permeable, even after several days in water,
      are referred to as 'hard', 'stone', or 'impermeable' seeds. What prevents soybean
      hard seeds from taking up water? Previous work established that the initial
      imbibition of soft soybean seeds correlates with the presence of small cracks in
      the outermost cuticle that covers the seed coat, prompting a detailed analysis of
      soybean seed coat cutin. In this paper, it is shown that the outermost cuticle of
      the seed coat has an unusual chemical composition, lacking typical mid-chain
      hydroxylated fatty acids but being relatively rich in other types of hydroxylated
      fatty acids. The cuticle of the impermeable cultivar studied contained a
      disproportionately high amount of hydroxylated fatty acids relative to that of
      the permeable ones. Moreover, a brief treatment with hot alkali released the
      omega-hydroxy fatty acid component of the outermost cuticle and created holes in
      it that caused the seeds to become permeable. This demonstrates that the
      outermost cuticle of the seed is the critical structure that prevents water
      uptake by hard seeds.

PMID- 17218547
TI  - Know your long-term care hospital.

PMID- 17218548
TI  - How do we explain unexplained pulmonary hypertension in the elderly?

PMID- 17218549
TI  - Wedge resection: when a little is not enough.

PMID- 17218550
TI  - Obesity-hypoventilation syndrome and noninvasive mechanical ventilation: new
      insights in the Pickwick papers?

PMID- 17218551
TI  - Antibiotic treatment of exacerbations of COPD: a randomized, controlled trial
      comparing procalcitonin-guidance with standard therapy.
AB  - BACKGROUND: Therapy with antibiotics influences recovery only in selected cases
      of COPD exacerbations. We evaluated the efficacy and safety of procalcitonin
      guidance compared to standard therapy with antibiotic prescriptions in patients
      experiencing exacerbations of COPD. METHODS: A total of 208 consecutive patients
      requiring hospitalization for COPD exacerbation were randomized at the index
      exacerbation to procalcitonin-guided or standard antibiotic therapy. Patients
      receiving procalcitonin-guided therapy were treated with antibiotics according to
      serum procalcitonin levels; standard-therapy patients received antibiotics
      according to the attending physician. The primary outcome was the antibiotic
      exposure at the index exacerbation and the subsequent antibiotic requirement for
      COPD exacerbation within 6 months. Secondary outcomes were clinical recovery,
      symptom scores, length of hospitalization, ICU stay, death, lung function,
      exacerbation rate, and time to next exacerbation. RESULTS: At the index
      exacerbation, procalcitonin guidance reduced antibiotic prescription (40% vs 72%,
      respectively; p < 0.0001) and antibiotic exposure (relative risk [RR], 0.56; 95%
      confidence interval [CI], 0.43 to 0.73; p < 0.0001) compared to standard therapy.
      Moreover, procalcitonin guidance at the index exacerbation allowed a significant
      sustained reduction in total antibiotic exposure for up to 6 months (RR, 0.76;
      95% CI, 0.64 to 0.92; p = 0.004). Clinical outcome and improvement in FEV(1) at
      14 days and 6 months did not differ between groups. Within 6 months, the
      exacerbation rate (0.62 vs 0.64, respectively), the rehospitalization rate (0.21
      vs 0.24, respectively), and mean (+/- SD) time to the next exacerbation (70.0 +/-
      46.1 vs 70.4 +/- 51.9 days, respectively; p = 0.523) were similar in both groups.
      CONCLUSIONS: Procalcitonin guidance for exacerbations of COPD offers a sustained
      advantage over standard therapy in reducing antibiotic use for up to 6 months
      with a number-needed-to-treat of 3.

PMID- 17218552
TI  - Risk indexes for exacerbations and hospitalizations due to COPD.
AB  - OBJECTIVE: The ability to predict exacerbations in patients with COPD might
      permit more rational use of preventive interventions. Our objective was to
      develop risk indexes for exacerbations and hospitalizations due to exacerbations
      that might be applied to the individual patient. METHODS: Spirometry,
      demographics, and medical history were obtained at baseline in 1,829 patients
      with moderate-to-very severe COPD who entered a trial of inhaled tiotropium.
      Information about exacerbations and hospitalizations due to exacerbation was
      collected during the 6-month follow-up period. Analyses of first outcomes were
      modeled using univariable and multivariable Cox proportional hazards regressions.
      RESULTS: During follow-up, 551 patients had at least one exacerbation and 151
      patients had at least one hospitalization due to exacerbation. In the
      multivariable model for exacerbation, older age, percentage of predicted FEV(1),
      duration of COPD, a productive cough, antibiotic or systemic corticosteroid use
      for COPD in the prior year, hospitalization for COPD in the prior year, and
      theophylline use at baseline predicted a higher risk. In the multivariable model
      for hospitalization, older age, percentage of predicted FEV(1), unscheduled
      clinic/emergency department visits for COPD in the prior year, any cardiovascular
      comorbidity, and prednisone use at baseline were associated with greater risk.
      Both the exacerbation and the hospitalization models provided moderately good
      discrimination, the validated concordance indexes being 0.66 and 0.73,
      respectively. Methods for calculating risk in individual patients are provided.
      CONCLUSIONS: Spirometry along with a few questions directed to the patient are
      strongly predictive of exacerbations and related hospitalizations over the
      ensuing 6 months.

PMID- 17218553
TI  - COPD prevalence in Salzburg, Austria: results from the Burden of Obstructive Lung
      Disease (BOLD) Study.
AB  - BACKGROUND: COPD is projected to be the third leading cause of death worldwide by
      2020. The Burden of Obstructive Lung Disease initiative was started to measure
      the prevalence of COPD in a standardized way and to provide estimates of the
      social and economic burden of disease. METHODS: We surveyed a gender-stratified,
      population-based sample of 2,200 adults >or= 40 years of age. The findings of
      prebronchodilator and postbronchodilator spirometry, as well as information on
      smoking and reported respiratory disease was recorded. Irreversible airflow
      obstruction was defined as a postbronchodilator FEV(1)/FVC ratio of < 0.70.
      RESULTS: For 1,258 participants with good-quality postbronchodilator spirometry
      findings, the overall prevalence of COPD at stage I or higher was 26.1%, and was
      equal in men and women. The prevalence of COPD stage II or higher (FEV(1)/FVC
      ratio, < 0.7; FEV(1), < 80% predicted) was 10.7%. The prevalence of COPD stage
      I+, and COPD stage II+, increased with age and cigarette smoking. A doctor
      diagnosis of COPD was reported by only 5.6% of participants. CONCLUSION: One
      quarter of residents of Salzburg County (Austria) who were >or= 40 years of age
      had at least mild irreversible airflow obstruction. The high prevalence of COPD
      highlights the impending health-care crisis that will affect many countries as a
      result of this greatly underappreciated condition.

PMID- 17218555
TI  - A 1-year prospective study of the infectious etiology in patients hospitalized
      with acute exacerbations of COPD.
AB  - INTRODUCTION: Infection is a major cause of acute exacerbations of COPD
      (AECOPDs). We aimed to study the infectious etiology related to AECOPD. METHODS:
      Patients admitted to an acute care hospital in Hong Kong with an AECOPD were
      recruited prospectively from May 1, 2004, to April 30, 2005. Sputum samples,
      nasopharyngeal aspirate (NPA) samples, and paired serology specimens were
      collected. Spirometry was performed with patients in the stable phase 2 to 3
      months after hospital discharge. RESULTS: There were 643 episodes of AECOPD among
      373 patients. Their mean age was 75.3 years (SD, 7.9 years) with 307 male
      patients. The mean FEV(1) was 40.4% predicted (SD, 18.7% predicted), and the mean
      FEV(1)/FVC ratio was 58.4% (SD, 16.0%). Among sputum samples from the 530
      episodes of AECOPD hospital admissions that were saved, 13.0%, 6.0%, and 5.5%,
      respectively, had positive growth of Haemophilus influenzae, Pseudomonas
      aeruginosa, and Streptococcus pneumoniae. Among the 505 hospital admissions with
      patients who had NPA samples saved, 5.7%, 2.3%, 0.8%, and 0.8%, respectively, had
      influenza A, respiratory syncytial virus (RSV), influenza B, and parainfluenza 3
      isolated from viral cultures. Paired serology test results revealed a fourfold
      rise in viral titers in 5.2%, 2.2%, and 1.4% of patients, respectively, for
      influenza A, RSV, and influenza B. Very severe airflow obstruction (stable-state
      spirometry) was associated with a higher chance of a positive sputum culture
      (FEV(1) >/= 30% predicted, 28.2%; FEV(1) < 30% predicted, 40.4%; p = 0.006).
      CONCLUSION: H influenzae and influenza A were the most common etiologic agents in
      patients who were hospitalized with AECOPDs. More severe airflow obstruction was
      associated with a higher chance of a positive sputum culture finding.

PMID- 17218554
TI  - Systemic cytokines, clinical and physiological changes in patients hospitalized
      for exacerbation of COPD.
AB  - BACKGROUND: Systemic inflammation in patients with COPD may worsen during
      exacerbations, but there is limited information relating levels of systemic
      inflammatory markers with symptoms and physiologic changes during an exacerbation
      METHODS: We measured dyspnea using the visual analog scale, pulmonary function
      tests, hemograms, and plasma levels for interleukin (IL)-6, IL-8, leukotriene
      B(4) (LTB4), tumor necrosis factor-alpha, and secretory leukocyte protease
      inhibitor (SLPI) in 20 patients on admission to a hospital for exacerbation of
      COPD (ECOPD), 48 h later (interim), and 8 weeks after hospital discharge
      (recovery). RESULTS: Dyspnea was present in all patients. Inspiratory capacity
      improved faster than FEV(1). Compared to recovery, there was a significant
      increase in the mean (+/- SD) hospital admission plasma levels of IL-6 (6.38 +/-
      0.72 to 2.80 +/- 0.79 pg/mL; p = 0.0001), IL-8 (8.18 +/- 0.85 to 3.72 +/- 0.85
      pg/mL; p = 0.002), and LTB4 (8,675 +/- 1,652 to 2,534 +/- 1,813 pg/mL; p =
      0.003), and the percentages of segmented neutrophils (79 to 69%; p < 0.02) and
      band forms (7.3 to 1.0%; p < 0.01) in peripheral blood, with no changes in TNF
      alpha and SLPI. There were significant correlations between changes in IL-6 (r =
      0.61; p = 0.01) and IL-8 (r = 0.56; p = 0.04) with changes in dyspnea and levels
      of IL-6 (r = -0.51; p = 0.04) and TNF-alpha (r = -0.71; p < 0.02) with changes in
      FEV(1.) CONCLUSIONS: Hospitalized patients with ECOPDs experience significant
      changes in systemic cytokine levels that correlate with symptoms and lung
      function. An ECOPD represents not only a worsening of airflow obstruction but
      also increased systemic demand in a host with limited ventilatory reserve.

PMID- 17218556
TI  - Small airways dysfunction and neutrophilic inflammation in bronchial biopsies and
      BAL in COPD.
AB  - BACKGROUND: The single-breath N(2) test (sbN(2)-test) is closely related to small
      airways pathology in resected lung specimens of smokers. We investigated whether
      uneven ventilation and airway closure are associated with specific markers of
      airway inflammation as obtained by bronchial biopsies, BAL, and induced sputum in
      patients with manifest COPD. METHODS: Fifty-one patients with stable COPD not
      receiving corticosteroids were examined in a cross-sectional study (43 men; mean
      [SD] age, 63 +/- 8 years; exsmokers and smokers; median pack-years, 41
      [interquartile range, 31 to 51 pack-years]). Postbronchodilator spirometry
      (FEV(1), 63 +/- 8% of predicted) and sbN(2)-test (slope of phase III [DeltaN(2)],
      closing capacity [CC]/total lung capacity [TLC] percentage of predicted) were
      performed. Inflammatory cell counts were assessed in bronchial biopsies, BAL
      (only in the first half of patients), and induced sputum. Neutrophil elastase
      (NE), secretory leukocyte proteinase inhibitor (SLPI), and interleukin-8 levels
      were determined in BAL fluid. RESULTS: DeltaN(2) increased with subepithelial
      neutrophil numbers in bronchial biopsies (rs = 0.337, p = 0.017) and with NE
      levels (rs = 0.443, p = 0.039), NE/neutrophil ratio (rs = 0.575, p = 0.005) and
      SLPI levels (rs = 0.484, p = 0.022) in BAL. CC/TLC was associated with BAL
      neutrophil numbers (rs = 0.448, p = 0.048). The sbN(2)-test was not associated
      with any other inflammatory cell type in BAL or biopsies, nor with inflammatory
      cell counts in sputum. Of importance, the correlations between DeltaN(2) and BAL
      NE/neutrophil ratio, and between CC/TLC and BAL neutrophil numbers remained
      significant when adjusting for FEV(1) percentage of predicted. CONCLUSIONS: The
      results of the sbN(2)-test are associated with neutrophilic inflammation in
      bronchial biopsies and BAL in patients with COPD. Our findings support a role of
      neutrophilic inflammation in the pathogenesis of small airways dysfunction in
      COPD.

PMID- 17218557
TI  - Diagnostic labeling of COPD in five Latin American cities.
AB  - BACKGROUND: COPD is a major worldwide problem with a rising prevalence. Despite
      its importance, there is a lack of information regarding underdiagnosis and
      misdiagnosis of COPD in different countries. As part of the Proyecto
      Latinoamericano de Investigacion en Obstruccion Pulmonar study, we examined the
      relationship between prior diagnostic label and airway obstruction in the
      metropolitan areas of five Latin American cities (Sao Paulo, Santiago, Mexico
      City, Montevideo, and Caracas). METHODS: A two-stage sampling strategy was used
      in each of the five areas to obtain probability samples of adults aged >or= 40
      years. Participants completed a questionnaire that included questions on prior
      diagnoses, and prebronchodilator and postbronchodilator spirometry. A study
      diagnosis of COPD was based on airway obstruction, defined as a
      postbronchodilator FEV(1)/FVC < 0.70. RESULTS: Valid spirometry and prior
      diagnosis information was obtained for 5,303 participants; 758 subjects had a
      study diagnosis of COPD, of which 672 cases (88.7%) had not been previously
      diagnosed. The prevalence of undiagnosed COPD was 12.7%, ranging from 6.9% in
      Mexico City to 18.2% in Montevideo. Among 237 subjects with a prior COPD
      diagnosis, only 86 subjects (36.3%) had postbronchodilator FEV(1)/FVC < 0.7,
      while 151 subjects (63.7%) had normal spirometric values. In the same group of
      237 subjects, only 34% reported ever undergoing spirometry prior to our study.
      CONCLUSIONS: Inaccurate diagnostic labeling of COPD represents an important
      health problem in Latin America. One possible explanation is the low rate of
      spirometry for COPD diagnosis.

PMID- 17218558
TI  - Transferring critically ill patients out of hospital improves the standardized
      mortality ratio: a simulation study.
AB  - BACKGROUND: Transferring critically ill patients to other acute care hospitals
      may artificially impact benchmarking measures. We sought to quantify the effect
      of out-of-hospital transfers on the standardized mortality ratio (SMR), an
      outcome-based measure of ICU performance. METHODS: We performed a cohort study
      and Monte Carlo simulation using data from 85 ICUs participating in the acute
      physiology and chronic health evaluation (APACHE) clinical information system
      from 2002 to 2003. The SMR (observed divided by expected hospital mortality) was
      calculated for each ICU using APACHE IV risk adjustment. A set number of patients
      was randomly assigned to be transferred out alive rather than experience their
      original outcome. The SMR was recalculated, and the mean simulated SMR was
      compared to the original. RESULTS: The mean (+/- SD) baseline SMR was 1.06 +/-
      0.19. In the simulation, increasing the number of transfers by 2% and 6% over
      baseline decreased the SMR by 0.10 +/- 0.03 and 0.14 +/- 0.03, respectively. At a
      2% increase, 27 ICUs had a decrease in SMR of > 0.10, and two ICUs had a decrease
      in SMR of > 0.20. Transferring only one additional patient per month was enough
      to create a bias of > 0.1 in 27 ICUs. CONCLUSIONS: Increasing the number of acute
      care transfers by a small amount can significantly bias the SMR, leading to
      incorrect inference about ICU quality. Sensitivity to the variation in hospital
      discharge practices greatly limits the use of the SMR as a quality measure.

PMID- 17218559
TI  - Ventilator-dependent survivors of catastrophic illness transferred to 23 long
      term care hospitals for weaning from prolonged mechanical ventilation.
AB  - STUDY OBJECTIVES: This multicenter study was undertaken to characterize the
      population of ventilator-dependent patients admitted to long-term care hospitals
      (LTCHs) for weaning from mechanical ventilation. DESIGN: Observational study with
      concurrent data collection. Characteristics of the LTCHs were also surveyed.
      SETTING: Twenty-three LTCHs in the United States. PATIENTS: Consecutive
      ventilator-dependent patients admitted over a 1-year period: March 1, 2002, to
      February 28, 2003. RESULTS: A total of 1,419 patients were enrolled in the
      Ventilation Outcomes Study. Median age of the patients was 71.8 years old (range,
      18 to 97.7 years), with an equal gender distribution. The premorbid domicile was
      home or assisted living in 86.5%; "good" premorbid functional status (Zubrod
      score 0-2) was assessed in 77%. There was a history of smoking in 59% (mean, 57
      +/- 42 pack-years [+/- SD]); premorbid diagnoses averaged 2.6 per patient.
      Patients came to the LTCH after mean of 33.8 +/- 29 days at the transferring
      hospital; mean time to tracheotomy was 15.0 +/- 10 days. A medical illness led to
      ventilator dependency in 60.8% of patients; a surgical procedure led to
      ventilatory dependency in 39.2%. On admission to the LTCH, the median acute
      physiology score of APACHE (acute physiology and chronic health evaluation) III
      was 35 (range, 4 to 115); > 90% of patients had at least three penetrating
      indwelling tubes/catheters; 42% of patients had stage 2 or higher pressure
      ulceration. CONCLUSIONS: This is the first multicenter study to characterize
      ventilator-dependent survivors of catastrophic illness admitted to the post-ICU
      venue of LTCHs for weaning from prolonged mechanical ventilation (PMV). Overall,
      our findings suggest that ventilator-dependent patients admitted to LTCHs for
      weaning will continue to require considerable medical interventions and
      treatments, owing to the burden of acute-on-chronic diseases resulting in PMV.

PMID- 17218560
TI  - Post-ICU mechanical ventilation at 23 long-term care hospitals: a multicenter
      outcomes study.
AB  - STUDY OBJECTIVES: This multicenter study was undertaken to characterize the
      population of ventilator-dependent patients admitted to long-term care hospitals
      (LTCHs) with weaning programs, and to report treatments, complications, weaning
      outcome, discharge disposition, and survival in these patients. DESIGN:
      Observational study with concurrent data collection. SETTING: Twenty-three LTCHs
      in the United States. PATIENTS: Consecutive ventilator-dependent patients
      admitted over a 1-year period: March 1, 2002, to February 28, 2003. RESULTS: A
      total of 1,419 patients were enrolled in the Ventilation Outcomes Study. Median
      age of patients was 71.8 years (range, 18 to 97.7 years). Patients averaged 6.9
      procedures and treatments during the LTCH hospitalization; median length of stay
      was 40 days (range, 1 to 365 days). Seven of the 10 most frequent complications
      treated at the LTCH were infections; congestive heart failure and diabetes
      mellitus were the most common comorbidities requiring treatment. Outcomes of
      weaning attempts, scored at LTCH discharge, were 54.1% weaned, 20.9% ventilator
      dependent, and 25.0% deceased. Median time to wean (n = 766) was 15 days (range,
      7 to 30 days). Discharge disposition included 28.8% to home, 49.2% to
      rehabilitation and extended-care facilities, and 19.5% to short-stay acute
      hospitals. Nearly one third of patients were known to be alive 12 months after
      admission to the LTCH. CONCLUSIONS: Patients admitted to LTCHs for weaning
      attempts were elderly, with acute-on-chronic diseases, and continued to require
      considerable medical interventions and treatments. The frequency and type of
      complications were not surprising following prolonged and aggressive ICU
      interventions. In the continuum of critical care medicine, more than half of
      ventilator-dependent survivors of catastrophic illness transferred from the ICU
      were successfully weaned from prolonged mechanical ventilation in the setting of
      an LTCH.

PMID- 17218561
TI  - Unexplained pulmonary hypertension in elderly patients.
AB  - BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) preferentially
      affects young women. However, a subset of patients with IPAH is elderly. Our
      objective was to compare elderly (age >/= 65 years) vs younger persons with
      unexplained pulmonary hypertension (PH) and a presumptive diagnosis of IPAH.
      METHODS: Clinical, echocardiographic, hemodynamic, and survival data were
      collected on consecutive patients with suspected IPAH after evaluation in a large
      tertiary center PH clinic. RESULTS: Of 197 patients (mean age +/- SD, 52 +/- 16
      years; 80% female), 48 patients (24%) were elderly. Elderly and younger patients
      had similar symptom severity, systolic pulmonary artery (PA) pressure (82.7 +/-
      20.3 mm Hg vs 86.9 +/- 18.8 mm Hg, respectively; p = 0.21), and severity of right
      ventricular enlargement and dysfunction. Elderly patients had higher pulmonary
      capillary wedge pressure (PCWP) [15.3 +/- 7.3 mm Hg vs 11.1 +/- 5.3 mm Hg; p <
      0.0001] and more frequently failed (56%) to meet hemodynamic criteria for IPAH
      (PH with PCWP < 15 mm Hg) than did younger patients (19%). Elderly patients also
      had higher systemic systolic (p < 0.0001) and pulse (p < 0.0001) pressures and
      more cardiovascular disease. Among those patients with normal PCWP, elderly
      patients had worse survival than young patients (p = 0.007). Among those patients
      with elevated PCWP, elderly patients had lower PA pressures (p = 0.04) and better
      survival (p = 0.02). CONCLUSIONS: Elderly patients with clinically suspected IPAH
      often fail to meet hemodynamic criteria for IPAH due to elevated PCWP. Studies to
      define the proper diagnostic strategy and the safety and efficacy of pulmonary
      vasodilators in elderly patients with unexplained PH are needed.

PMID- 17218562
TI  - Endothelin-1/endothelin-3 ratio: a potential prognostic factor of pulmonary
      arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare condition
      characterized by elevated pulmonary artery pressure leading to right-heart
      failure and death. Endothelin (ET)-1 has been shown to play a significant
      pathogenic role in PAH. ET-3 has not yet been investigated in PAH. METHODS: ET-1
      and ET-3 plasma concentrations were measured in 33 PAH patients prior to any
      specific PAH therapy and in 9 control subjects. In PAH patients, hemodynamic
      parameters measured by right-heart catheterization, 6-min walk distance (6MWD),
      New York Heart Association (NYHA) functional class, and time until lung
      transplantation or death were recorded. RESULTS: In patients with PAH, levels of
      ET-1 were increased while those of ET-3 were decreased, as compared to control
      subjects (p < 0.005 for both comparisons). ET-1/ET-3 ratio varied little in
      control subjects, while it increased threefold in PAH patients (p < 0.0001). ET-1
      correlated positively with right atrial pressure (RAP), indexed total pulmonary
      resistance, and negatively with cardiac index and venous saturation of oxygen
      (Svo(2)). ET-3 correlated positively with 6MWD. ET-1/ET-3 ratio correlated
      positively with RAP, negatively with Svo(2) and 6MWD, and was also associated
      with NYHA functional class. ET-1/ET-3 ratio was associated with prognosis in this
      sample of PAH patients treated with specific therapies. CONCLUSIONS: PAH is
      characterized by elevated ET-1 and ET-1/ET-3 ratio and decreased ET-3 plasma
      concentrations. All of them correlate with hemodynamic and clinical markers of
      disease severity. ET-1/ET-3 ratio might be a novel prognostic factor in PAH.
      These preliminary data should be validated in a large prospective multicenter
      cohort of PAH patients.

PMID- 17218563
TI  - Predictors of nocturnal oxygen desaturation in pulmonary arterial hypertension.
AB  - BACKGROUND: Sleep may be associated with significant respiratory compromise in
      patients with lung disease and can result in hypoxia. In patients with pulmonary
      arterial hypertension (PAH), nocturnal desaturation may not be reflected in
      daytime evaluations of oxygenation and can lead to worsening pulmonary
      hemodynamics. The study was conducted to determine the prevalence and
      significance of nocturnal oxygen desaturation in patients with PAH. METHODS: A
      cross-sectional study conducted at the Cleveland Clinic. Patients were followed
      up at our institution except for the overnight oximetry study done at home. Data
      regarding degree of nocturnal desaturation, demographics, hemodynamics, pulmonary
      function, and functional capacity were collected. RESULTS: Forty-three patients
      (mean age, 47.9 +/- 13.5 years [+/- SD]; 36 women and 7 men) underwent nocturnal
      oximetry. The etiology of PAH included idiopathic PAH (88%) and PAH associated
      with connective tissue diseases (12%). The majority of patients were New York
      Heart Association functional class II (42%) or III (53%). Thirty patients (69.7%)
      spent > 10% of sleep time with oxygen saturation by pulse oximetry < 90%.
      Desaturators were older (p = 0.024) and had higher hemoglobin (p = 0.002).
      Sixteen of 27 patients (59%) without desaturation < 90% during a 6-min walk test
      were nocturnal desaturators. Nocturnal desaturators had higher brain natriuretic
      protein (p = 0.004), lower cardiac index (p = 0.03), and higher mean right atrial
      pressure (p = 0.09), mean pulmonary artery pressure, and pulmonary vascular
      resistance. On echocardiography, desaturators were more likely to have moderate
      or severe right ventricular dilation (p = 0.04) and pericardial effusion. Only
      one patient had significant sleep apnea. CONCLUSIONS: Nocturnal hypoxemia is
      common in PAH patients and correlates with advanced pulmonary hypertension and
      right ventricular dysfunction. Approximately 60% patients without exertional
      hypoxia had nocturnal desaturation. Overnight oximetry should be considered in
      the routine workup of PAH patients who do not demonstrate exertional
      desaturation.

PMID- 17218564
TI  - Familial premature coronary artery disease mortality and obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is linked to both coronary artery
      disease (CAD) and sudden death, but any causal role remains unclear. A family
      history of premature CAD and related mortality is an independent risk factor for
      the development of CAD. We hypothesized that OSA is associated with a family
      history of premature mortality from ischemic heart disease. METHODS: We
      prospectively studied 588 subjects who underwent polysomnography from May 2000 to
      June 2004. Demographics, comorbidities, family history of cardiovascular disease,
      and the ages and causes of death for 10 strata of family members were recorded
      for all subjects. We excluded those subjects with known causes of premature
      cardiac death, such as hypertrophic cardiomyopathy and long-QT syndrome. OSA was
      defined by American Academy of Sleep Medicine criteria (ie, apnea-hypopnea index
      >or= 5). Premature CAD mortality was defined as death due to ischemic heart
      disease or sudden cardiac death before 55 years of age (men) or 65 years of age
      (women). RESULTS: Polysomnography confirmed OSA in 316 subjects and excluded it
      in 202 subjects. The unadjusted odds ratio (OR) for OSA and a family history of
      premature CAD mortality was 2.11 (95% confidence interval [CI], 1.10 to 4.31; p =
      0.031). After adjusting for each subject's sex, body mass index, and history of
      CAD, there was a significant and independent association between OSA and family
      history of premature CAD mortality (OR, 2.13; 95% CI, 1.04 to 4.66; p = 0.046).
      CONCLUSIONS: Regardless of their own CAD status, people with OSA are more likely
      than those without OSA to have a family history of premature CAD mortality.

PMID- 17218565
TI  - Lung aeration during sleep.
AB  - BACKGROUND: During sleep, ventilation and functional residual capacity (FRC)
      decrease slightly. This study addresses regional lung aeration during wakefulness
      and sleep. METHODS: Ten healthy subjects underwent spirometry awake and with
      polysomnography, including pulse oximetry, and also CT when awake and during
      sleep. Lung aeration in different lung regions was analyzed. Another three
      subjects were studied awake to develop a protocol for dynamic CT scanning during
      breathing. RESULTS: Aeration in the dorsal, dependent lung region decreased from
      a mean of 1.14 +/- 0.34 mL (+/- SD) of gas per gram of lung tissue during
      wakefulness to 1.04 +/- 0.29 mL/g during non-rapid eye movement (NREM) sleep (-
      9%) [p = 0.034]. In contrast, aeration increased in the most ventral,
      nondependent lung region, from 3.52 +/- 0.77 to 3.73 +/- 0.83 mL/g (+ 6%) [p =
      0.007]. In one subject studied during rapid eye movement (REM) sleep, aeration
      decreased from 0.84 to 0.65 mL/g (- 23%). The fall in dorsal lung aeration during
      sleep correlated to awake FRC (R(2) = 0.60; p = 0.008). Airway closure, measured
      awake, occurred near and sometimes above the FRC level. Ventilation tended to be
      larger in dependent, dorsal lung regions, both awake and during sleep (upper
      region vs lower region, 3.8% vs 4.9% awake, p = 0.16, and 4.5% vs 5.5% asleep, p
      = 0.09, respectively). CONCLUSIONS: Aeration is reduced in dependent lung regions
      and increased in ventral regions during NREM and REM sleep. Ventilation was more
      uniformly distributed between upper and lower lung regions than has previously
      been reported in awake, upright subjects. Reduced respiratory muscle tone and
      airway closure are likely causative factors.

PMID- 17218566
TI  - Relationship between beta-blocker treatment and the severity of central sleep
      apnea in chronic heart failure.
AB  - BACKGROUND: We sought to examine the relationship between use of beta-blockers
      and the severity of central sleep apnea (CSA) in patients with chronic heart
      failure. METHODS: We performed polysomnography in 45 patients with chronic heart
      failure (New York Heart Association functional class II/III and left ventricular
      ejection fraction < 50%) and examined the relationship between use of beta
      blockers and the severity of CSA. Central apnea index (CAI) was used as an
      indicator of CSA. RESULTS: Patients receiving beta-blockers (ie, carvedilol; n =
      27) had lower apnea-hypopnea index (AHI) and CAI than patients not receiving beta
      blockers (n = 18) [mean +/- SD, 14 +/- 11 vs 33 +/- 17, p < 0.0001; and 1.9 +/-
      3.2 vs 11 +/- 12, p = 0.0004, respectively]. AHI and CAI were negatively
      correlated with the dose of carvedilol (Spearman rho = - 0.61, p < 0.0001; and
      Spearman rho = - 0.57, p = 0.0002, respectively). Multiple regression analysis
      selected no use of beta-blockers as an independent factor of CAI (p = 0.0006). In
      five patients with CAI > 5 who underwent serial sleep studies, CAI decreased
      significantly after 6 months of treatment with carvedilol (9.5 +/- 4.9 to 1.3 +/-
      2.4, p = 0.03). CONCLUSIONS: In patients with chronic heart failure, CAI was
      lower according to the dose of beta-blockers, and no use of beta-blockers was
      independently associated with CAI. In addition, 6 months of treatment with
      carvedilol decreased CAI. These results suggest that beta-blocker therapy may
      dose-dependently suppress CSA in patients with chronic heart failure.

PMID- 17218567
TI  - Wedge resection vs lobectomy: 10-year survival in stage I primary lung cancer.
AB  - BACKGROUND: The selection of lobectomy or wedge resection in the treatment of
      patients with stage I primary lung cancer remains controversial. Clinical
      judgment based on comorbidities remains the main decision factor. We investigated
      the impact of procedure on long-term survival in a multicenter retrospective
      analysis. METHODS: The records of 289 patients who underwent surgical resection
      of stage I primary lung cancer between 1993 and 1998 at three tertiary medical
      centers were reviewed for age, sex, type of resection, tumor size, number of
      lymph nodes dissected, pathology, and recurrence. Long-term survival was obtained
      through the Federal Social Security Death Index and Cancer Registries. Kaplan
      Meier, Wilcox, logistic regression, and power and t test analyses were used to
      examine survival, predictors of mortality, and correlations. RESULTS: A total of
      215 patients underwent lobectomy, and 74 underwent wedge resection. The groups
      were similar with respect to age, tumor size, and other comorbidities. Overall,
      there was a nonsignificant trend toward better survival times in patients after
      lobectomy vs wedge resection (mean [+/- SD] survival time, 5.8 +/- 0.3 vs 4.1 +/-
      0.3 years, respectively; p = 0.112). This trend gained significance in smaller
      cancers, where patients who underwent lobectomy for tumors < 3 cm in size had
      better survival times compared to those who underwent wedge resection (p =
      0.029). CONCLUSION: Although the overall difference in survival time between
      patients undergoing lobectomy and those undergoing wedge resection was not
      significant, patients with tumors < 3 cm in size had improved survival times
      after undergoing lobectomy. Thus, tumor size appears to be an important factor to
      be considered in preoperative planning. Randomized trials are necessary to
      confirm the superiority of lobectomy over wedge resection for stage IA lung
      cancers.

PMID- 17218568
TI  - Evaluation of expiratory volume, diffusion capacity, and exercise tolerance
      following major lung resection: a prospective follow-up analysis.
AB  - BACKGROUND: Lung resections determine a variable functional reduction depending
      on the extent of the resection and the time elapsed from the operation. The
      objectives of this study were to prospectively investigate the postoperative
      changes in FEV(1), carbon monoxide lung diffusion capacity (Dlco), and exercise
      tolerance after major lung resection at repeated evaluation times. METHODS:
      FEV(1), Dlco, and peak oxygen consumption (Vo(2)peak) calculated using the stair
      climbing test were measured in 200 patients preoperatively, at discharge, and 1
      month and 3 months after lobectomy or pneumonectomy. Preoperative and repeated
      postoperative measures were compared, and a time-series, cross-sectional
      regression analysis was performed to identify factors associated with
      postoperative Vo(2)peak. RESULTS: One month after lobectomy, FEV(1), Dlco, and
      Vo(2)peak values were 79.5%, 81.5%, and 96% of preoperative values and recovered
      up to 84%, 88.5%, and 97% after 3 months, respectively. One month after
      pneumonectomy, FEV(1) percentage of predicted, Dlco percentage of predicted, and
      Vo(2)peak values were 65%, 75%, and 87% of preoperative values, and were 66%,
      80%, and 89% after 3 months, respectively. Three months after lobectomy, 27% of
      patients with COPD had improved FEV(1), 34% had improved Dlco, and 43% had
      improved Vo(2)peak compared to preoperative values. The time-series, cross
      sectional regression analysis showed that postoperative Vo(2)peak values were
      directly associated with preoperative values of Vo(2)peak, and postoperative
      values of FEV(1) and Dlco, and were inversely associated with age and body mass
      index. CONCLUSIONS: Our findings may be used during preoperative counseling and
      for deciding eligibility for operation along with other more traditional measures
      of outcome.

PMID- 17218569
TI  - Impaired objective daytime vigilance in obesity-hypoventilation syndrome: impact
      of noninvasive ventilation.
AB  - BACKGROUND: Obesity-hypoventilation syndrome (OHS) is efficiently treated by
      noninvasive ventilation (NIV). Sleep respiratory disturbances, reduced
      ventilatory drive, and excessive daytime sleepiness (EDS) are commonly reported,
      but their relationships remain unclear. OBJECTIVES: To characterize sleep
      breathing disorders encountered in patients with OHS, to compare low and normal
      CO(2) responders in terms of sleep abnormalities, subjective and objective
      measures of EDS, and to measure the changes induced by NIV on these parameters.
      METHODS: At baseline and after 5 nights of NIV, 15 consecutive patients (mean [+/
      SD] age, 55 +/- 9 years; mean body mass index, 38.7 +/- 6.1 kg/m(2); Paco(2),
      47.3 +/- 2.3 mm Hg) prospectively underwent polysomnography, CO(2) ventilatory
      response testing, Epworth sleepiness scale scoring, and the Oxford Sleep
      Resistance (OSLER) test, which is an objective vigilance test. RESULTS: OHS
      patients exhibited obstructive sleep apnea syndrome (mean apnea-hypopnea index,
      62 +/- 32 events per hour) and rapid eye movement (REM) sleep hypoventilation
      (mean REM sleep time, 35 +/- 33%). Baseline CO(2) sensitivity was significantly
      related to the proportion of hypoventilation during REM sleep (r = 0.54; p =
      0.037). Six patients showed abnormal sleep latencies during the OSLER test (71%
      of the low CO(2) responders vs 14% of the normal CO(2) responders). Low CO(2)
      responders exhibited significantly shorter sleep latencies during the OSLER test
      (23 +/- 14 vs 37 +/- 8 min, respectively; p = 0.05). Using NIV, diurnal blood gas
      levels were improved and REM sleep hypoventilation were suppressed. Objective
      sleepiness was improved in low CO(2) responders (p = 0.04). CONCLUSION: In OHS
      patients, the lower the daytime CO(2) response, the higher the proportion of REM
      sleep hypoventilation and daytime sleepiness. Short-term therapy with NIV
      improves all of these parameters.

PMID- 17218570
TI  - Effects of nocturnal noninvasive mechanical ventilation on heart rate variability
      of patients with advanced COPD.
AB  - BACKGROUND: Cardiovascular comorbidities have a negative impact on the health
      status and prognosis of patients with COPD. We determined whether nocturnal
      noninvasive (positive) mechanical ventilation (NIMV) can improve heart rate
      variability (HRV), decrease circulating natriuretic peptide levels, and improve
      functional performance of patients with very advanced COPD. METHODS: A
      randomized, double-blind, parallel controlled trial was conducted in 23
      participants with stable but advanced COPD. Participants received standard
      medical therapy plus nocturnal NIMV or standard medical therapy plus sham NIMV
      for 3 months. RESULTS: After 3 months of NIMV therapy, the 24-h triangular
      interpolation of N-N intervals increased from 322 to 473 ms (p = 0.034), the 24-h
      HRV index (HRVI) increased from 21.8 to 29.9 ms (p = 0.035), nocturnal HRVI
      increased from 6.1 to 8.0 ms (p = 0.026), and the SD of the average N-N interval
      increased from 37 to 41 ms (p = 0.020). None of these indexes changed
      significantly in the control group. Additionally, compared with the control
      group, the pro-atrial natriuretic peptide levels declined significantly in the
      NIMV group (p = 0.013). CONCLUSIONS: NIMV applied nocturnally over 3 months may
      improve HRV, reduce circulating natriuretic peptide levels, and enhance the
      functional performance of patients with advanced but stable COPD. While not
      definitive due to small sample size, these data suggest that nocturnal NIMV may
      reduce the impact of cardiac comorbidities in COPD patients.

PMID- 17218571
TI  - FEV1 performance among patients with acute asthma: results from a multicenter
      clinical trial.
AB  - OBJECTIVE: To determine the ability of patients seen for acute asthma
      exacerbations in the emergency department (ED) to perform good-quality FEV(1)
      measurements. METHODS: Investigators from 20 EDs were trained to perform
      spirometry testing as part of a clinical trial that included standardized
      equipment with special software-directed prompts. Spirometry was done on ED
      arrival and 30 min, 1 h, 2 h, and 4 h later, and during follow-up outpatient
      visits. MEASUREMENTS: Study performance criteria differed from American Thoracic
      Society (ATS) guidelines because of the population acuity and severity of illness
      as follows: ability to obtain acceptable FEV(1) measures (defined as two or more
      efforts with forced expiratory times >/= 2 s and time to peak flow < 120 ms or
      back-extrapolated volume < 5% of the FVC) and reproducibility criteria (two
      highest acceptable FEV(1) values within 10% of each other). RESULTS: Of the 620
      patients (age range, 12 to 65 years), > 90% met study acceptability criteria on
      ED arrival and 74% met study reproducibility criteria. Mean initial FEV(1) was
      38% of predicted. Spirometry quality improved over time; by 1 h, 90% of patients
      met study acceptability and reproducibility criteria. Patients with severe airway
      obstruction (FEV(1) < 25% of predicted) were initially less likely to meet
      quality goals, but this improved with time. The site was also an independent
      predictor of quality. CONCLUSION: When staff are well trained and prompt feedback
      regarding adequacy of efforts is given, modified ATS performance goals for FEV(1)
      tests can be met from most acutely ill adolescent and adult asthmatics, even
      within the first hour of evaluation and treatment for an asthma exacerbation.

PMID- 17218572
TI  - Uteroglobin-related protein 1 and clara cell protein in induced sputum of
      patients with asthma and rhinitis.
AB  - RATIONALE: Uteroglobin-related protein 1 (UGRP1) and Clara cell protein (CC16),
      members of the secretoglobin family, increasingly appear to play a role in airway
      inflammatory response. OBJECTIVE: To explore levels of UGRP1 and CC16 in induced
      sputum of patients with asthma and rhinitis. METHODS: Induced-sputum samples of
      patients with asthma or rhinitis (n = 32 each; atopic asthma, n = 24; atopic
      rhinitis, n = 20) and from 19 nonsmoking nonatopic control subjects were analyzed
      for cytology and levels of UGRP1, CC16, and albumin. MEASUREMENTS AND MAIN
      RESULTS: Sputum UGRP1 increased in both asthma and rhinitis, most strikingly so
      in asthma, in which changes were most significant in atopic individuals. By
      contrast, sputum CC16 did not change significantly in either condition, although
      it was positively correlated with UGRP1 in patients and control subjects. Changes
      in sputum UGRP1 in atopic asthma were not linked to permeability changes
      reflected by increased albumin levels but correlated positively with sputum
      macrophages and negatively with eosinophils. The observed differences in UGRP1
      and CC16 may be linked to different cell populations being responsible for their
      secretion; UGRP1 is mainly secreted in larger conducting airways, whereas CC16 is
      mainly secreted by the nasal and peripheral airways epithelium. CONCLUSIONS: The
      increase in UGRP1 but not of CC16 in asthma and rhinitis suggests that UGRP1 may
      play a role in these inflammatory diseases.

PMID- 17218573
TI  - The effect of montelukast on bronchial hyperreactivity in preschool children.
AB  - INTRODUCTION: The effect of montelukast therapy on bronchial hyperreactivity
      (BHR) as measured by the methacholine challenge test in preschool children has
      not yet been reported. OBJECTIVE: To determine the effect of montelukast (4 mg/d)
      on BHR as evaluated by a provocative concentration of a substance causing a 20%
      fall in FEV(1) (PC(20)) values in preschool asthmatic children. PATIENTS: A total
      of 26 preschool children (8 girls) aged 3.3 to 6.0 years (mean [+/- SD] age, 4.7
      +/- 0.8 years) with mild asthma. DESIGN: Double-blind randomized, placebo
      controlled, crossover study. Each child received 4 weeks of treatment with 4 mg
      of either montelukast or placebo separated by a 2-week washout period. Primary
      outcomes were PC(20) values and the stage number (triple dose) at which FEV(1)
      values dropped by 20%(.) Post-montelukast therapy PC(20) was compared to those
      for the post-placebo period. RESULTS: Following 4 weeks of montelukast treatment,
      the mean PC(20) was 4.79 +/- 4.69 mg/mL, while after 4 weeks of placebo the mean
      PC(20) was 2.07 +/- 2.37 mg/mL (p = 0.001). The montelukast/placebo ratio for
      PC(20) was 2.56 with a 95% confidence interval (CI) of 1.71 to 3.99. The median
      difference in stage was one triple dose with a 95% CI of 0.5 to 1.5. CONCLUSIONS:
      Four weeks of treatment with montelukast resulted in a decreased BHR compared
      with placebo.

PMID- 17218574
TI  - Aerosolized red-tide toxins (brevetoxins) and asthma.
AB  - BACKGROUND: With the increasing incidence of asthma, there is increasing concern
      over environmental exposures that may trigger asthma exacerbations. Blooms of the
      marine microalgae, Karenia brevis, cause red tides (or harmful algal blooms)
      annually throughout the Gulf of Mexico. K brevis produces highly potent natural
      polyether toxins, called brevetoxins, which are sodium channel blockers, and
      possibly histamine activators. In experimental animals, brevetoxins cause
      significant bronchoconstriction. In humans, a significant increase in self
      reported respiratory symptoms has been described after recreational and
      occupational exposures to Florida red-tide aerosols, particularly among
      individuals with asthma. METHODS: Before and after 1 h spent on beaches with and
      without an active K brevis red-tide exposure, 97 persons >or= 12 years of age
      with physician-diagnosed asthma were evaluated by questionnaire and spirometry.
      Concomitant environmental monitoring, water and air sampling, and personal
      monitoring for brevetoxins were performed. RESULTS: Participants were
      significantly more likely to report respiratory symptoms after K brevis red-tide
      aerosol exposure than before exposure. Participants demonstrated small, but
      statistically significant, decreases in FEV(1), midexpiratory phase of forced
      expiratory flow, and peak expiratory flow after exposure, particularly among
      those participants regularly using asthma medications. No significant differences
      were detected when there was no Florida red tide (ie, during nonexposure
      periods). CONCLUSIONS: This study demonstrated objectively measurable adverse
      changes in lung function from exposure to aerosolized Florida red-tide toxins in
      asthmatic subjects, particularly among those requiring regular therapy with
      asthma medications. Future studies will assess these susceptible subpopulations
      in more depth, as well as the possible long-term effects of these toxins.

PMID- 17218575
TI  - Responsiveness of patient-reported breathlessness during exercise in persistent
      asthma.
AB  - BACKGROUND: The purpose of the study was to examine the responsiveness of a
      computerized system whereby the patient reports spontaneously any change in the
      intensity of breathlessness during exercise. The hypotheses were that hypercapnia
      would increase and hyperoxia would decrease the slope of power production
      breathlessness ratings compared with a control condition during cycle ergometry.
      METHODS: Thirty adult subjects (15 women and 15 men) with persistent asthma (mean
      [+/- SD] FEV(1)/FVC ratio, 57 +/- 10%) completed an initial familiarization visit
      and three study visits. All subjects inhaled two puffs of albuterol (180 microg)
      in order to standardize lung function prior to exercise. At visits 2 to 4,
      subjects breathed one of the three gas mixtures administered in a random order
      while performing a ramp exercise test. The experimental conditions were as
      follows: hypercapnia (5% carbon dioxide); hyperoxia (40% oxygen); and control
      (room air). RESULTS: Lung function was the same before and after exercise with
      the three experimental conditions. With hypercapnia, peak ventilation was
      increased, peak oxygen consumption, and power production were reduced, the slope
      of power-breathlessness was increased, and 25 patients (83%) reported
      breathlessness as the limiting symptom. With hyperoxia, peak ventilation was
      decreased, peak power production and the slope of power-breathlessness were
      unchanged, and 16 patients (53%) reported leg discomfort as the limiting symptom.
      CONCLUSIONS: Breathing 5% carbon dioxide altered physiologic responses and the
      slope of power production-breathlessness during exercise. The responses to
      hyperoxia were inconsistent. The continuous method for patient-reported
      breathlessness was responsive to hypercapnia, but not to hyperoxia, during
      incremental exercise.

PMID- 17218576
TI  - A single dose of dexamethasone to prevent postbronchoscopy fever in children: a
      randomized placebo-controlled trial.
AB  - STUDY OBJECTIVE: To assess the effectiveness of one dose of dexamethasone (0.5
      mg/kg; maximum, 10 mg) to prevent fever after bronchoscopy with BAL. DESIGN:
      Randomized, placebo-controlled study. PATIENTS: Immunocompetent nonfebrile
      children undergoing fiberoptic bronchoscopy with BAL. MEASUREMENTS AND RESULTS:
      Sixty-nine children were included in the study. Thirty-eight children received
      saline solution, and 31 children received dexamethasone. The two groups were
      similar regarding the number of children < 2 years old, the percentage of
      abnormal bronchoscopic findings, the number of positive BAL culture findings, and
      the index of lipid-laden macrophages. Twenty-six children (68%) in the saline
      solution group (SG) had fever, compared to 3 children (9.6%) in the dexamethasone
      group (DG) [p < 0.001]. Fever after the procedure appeared later (12.3 +/- 5.5 h)
      in the DG compared to 5.4 +/- 2.7 h in the SG. CONCLUSIONS: One dose of
      dexamethasone administered prior to performing bronchoscopy with BAL may prevent
      fever subsequent to the procedure. Further studies are necessary in order to
      determine the optimal dosing regimen for dexamethasone when used for this
      purpose.

PMID- 17218577
TI  - Characteristics of trapped lung: pleural fluid analysis, manometry, and air
      contrast chest CT.
AB  - STUDY OBJECTIVES: To review the pleural fluid characteristics, pleural manometry,
      and radiographic data of patients who received a diagnosis of trapped lung in our
      pleural diseases service. DESIGN: Retrospective case series. METHODS: The
      procedure records of 247 consecutive patients who underwent pleural manometry at
      the Medical University of South Carolina between October 2002 and November 2005
      were reviewed. Eleven patients in whom a diagnostic pneumothorax was introduced
      were identified. Manometry data, radiographic findings, pleural fluid analysis,
      final clinical diagnosis, and information regarding the initial pleural insult
      were retrieved from the medical record. RESULTS: All 11 patients had a clinical
      diagnosis of trapped lung. The causes of trapped lung were attributed to coronary
      artery bypass graft surgery, uremia, thoracic radiation, pericardiotomy,
      spontaneous bacterial pleuritis and repeated thoracentesis, and complicated
      parapneumonic effusion. Mean pleural fluid pH was 7.30, pleural fluid lactate
      dehydrogenase (LDH) was 124 IU/L, and pleural fluid total protein was 2.9 g/dL.
      Pleural fluid was paucicellular with mononuclear cell predominance. Pleural space
      elastance was increased in all cases and ranged from 19 to 149 cm H(2)O/L of
      pleural fluid removed. All demonstrated abnormal visceral pleural thickness on
      air-contrast chest CT. CONCLUSIONS: Trapped lung is a clinical entity
      characterized by the presence of a restrictive visceral pleural peel that was
      first described in 1967. The pleural fluid is paucicellular, LDH is low, and
      protein may be in the exudative range. The elevated total pleural fluid protein
      may be related to factors other than active pleural inflammation or malignancy
      and does not exclude the diagnosis.

PMID- 17218578
TI  - Use of endobronchial valves for native lung hyperinflation associated with
      respiratory failure in a single-lung transplant recipient for emphysema.
AB  - Emphysema is a common indication for adult pulmonary transplantation. Double-lung
      transplantation is increasingly the preferred approach because severe
      posttransplant native lung hyperinflation (NLH) following single-lung
      transplantation may compromise allograft lung function. We describe successful
      emergency use of bronchoscopic lung volume reduction using endobronchial valves
      (EBVs) [Zephyr; Emphasys Medical; Redwood, CA] in a single-lung transplant
      recipient who was critically ill with ventilator dependence from complications of
      NLH and at excessive risk for lung volume reduction surgery or pneumonectomy.
      Following placement of 17 valves in all segments of the native lung, atelectasis
      of the native lung was accompanied by volume expansion of the allograft.
      Immediately following valve placement, peak airway pressure decreased and
      alveolar ventilation increased. The patient was subsequently weaned from
      mechanical ventilation. This report suggests the need for clinical trials to
      evaluate the effectiveness of EBVs in single-lung transplant recipients with less
      critical functional impairment associated with NLH.

PMID- 17218579
TI  - Six-minute walk test for the evaluation of pulmonary disease severity in
      scleroderma patients.
AB  - BACKGROUND: Pulmonary involvement is the leading cause of systemic sclerosis
      (SSc)-related deaths. A simple test to evaluate exercise capacity is the 6-min
      walk test (6MWT), and the walk distance is used as a primary outcome in clinical
      trials. Hemoglobin desaturation during a 6MWT is predictive of mortality in
      patients with primary pulmonary hypertension. Our objectives were to evaluate the
      walk distance and resting oxygen saturation - oxygen saturation after the 6-min
      period (DeltaSat) during the 6MWT in patients with SSc, and to establish
      correlations between the 6MWT results and other clinical variables. METHODS: We
      analyzed 110 SSc patients. DeltaSat was defined as a fall of end-of-test
      saturation >or= 4%. Clinical and demographic data were collected. All the
      patients were submitted to chest radiographs and high-resolution CT (HRCT) and
      underwent pulmonary function testing and echocardiography, and the presence of
      autoantibodies was determined. RESULTS: The variables associated with a walk
      distance < 400 m (p < 0.05) were age, dyspnea index, fibrosis on radiography,
      pulmonary arterial systolic pressure (PASP) >or= 30 mm Hg, and desaturation. The
      variables associated with DeltaSat (p < 0.05) were age, positive anti-Scl-70
      autoantibody, dyspnea index, fibrosis on radiography, FVC < 80% of predicted,
      PASP >or= 30 mm Hg, and ground-glass or reticular opacities on HRCT. In the
      multivariate logistic regression analysis, three variables were significant when
      tested with walk distance: age, race, and dyspnea index; four variables were
      significant when tested with DeltaSat: age, dyspnea index, positive anti-Scl-70
      autoantibody, and FVC < 80% of predicted. CONCLUSIONS: Desaturation during a 6MWT
      provides additional information regarding severity of disease in scleroderma
      patients with pulmonary manifestations.

PMID- 17218580
TI  - A prospective long-term study of 220 patients with a retrievable vena cava filter
      for secondary prevention of venous thromboembolism.
AB  - BACKGROUND: The immediate and long-term clinical events associated with the
      placement and removal of a retrievable filter (ALN filter; ALN Implants
      Chirurgicaux; Ghisonaccia, France) remain largely unknown. METHODS: This was a
      prospective cohort study with an 18-month follow-up. All consecutive patients
      scheduled for placement of an ALN filter between April 1999 and June 2005 in the
      Radiology Department of our hospital were included. RESULTS: During the study
      period, placement of an ALN filter was indicated in 220 patients (mean age, 70.8
      years), who were followed up for a median duration of 338.5 days (range, 1 to 561
      days); 148 patients (67.3%) completed the 18-month follow-up. No patients were
      unavailable for follow-up. All patients had an acute or past venous
      thromboembolism. Main indications were recurrent venous thromboembolism despite
      adequate anticoagulation therapy (10.9%), transient bleeding event (21.8%),
      definitive contraindication for anticoagulant therapy (26.8%), or obligation to
      stop anticoagulant therapy due to major surgery, major trauma, or invasive
      procedure (37.7%). Filter insertion was successful in 98.6% of patients and
      resulted in an immediate complication in 11.8%. The median duration of filter
      implantation was 166 days (first to third quartiles, 34 to 478 days). Meanwhile,
      17.0% (37 of 217 patients) had at least one venous thromboembolic event. Filter
      retrieval was attempted in 25.3% of patients after a median of 51 days (range, 6
      to 352 days); removal was successful at the first attempt in 92.7% of patients.
      CONCLUSIONS: The filter could be easily inserted and successfully removed up to 1
      year after insertion. Its safety and efficacy in preventing pulmonary embolism
      should be properly assessed in a randomized study.

PMID- 17218581
TI  - Risk factors for pulmonary Aspergillus terreus infection in patients with
      positive culture for filamentous fungi.
AB  - BACKGROUND: Invasive aspergillosis (IA) is a common fungal infection in
      immunocompromised patients and has a high mortality rate. Among patients with IA,
      Aspergillus terreus infections have become a growing concern in the past few
      years. OBJECTIVE: To determine the clinical risk factors for isolation of and
      respiratory infection by A terreus in patients with culture findings positive for
      filamentous fungi. METHODS: Cohort study of 505 consecutive isolates of
      filamentous fungi in 332 patients from one center. A terreus was present in 46
      isolates from 40 patients (9.1%). Clinical histories were reviewed to identify
      the risk factors related to isolation of and infection by A terreus, which were
      grouped into three categories (ie, host factors, factors related to
      immunosuppression, and factors related to hospitalization), and were analyzed
      using a multiple logistic regression model. RESULTS: A total of 192 of 505
      isolates studied (38%) were due to invasive respiratory infection. A total of 27
      of 46 cultures (58.7%) that were positive for A terreus were due to invasive
      infection (odds ratio [OR], 2.53; 95% confidence interval [CI], 1.37 to 4.69; p =
      0.034). The factors associated with invasive A terreus infection were
      prophylactic use of amphotericin B aerosols (OR, 27.8; 95% CI, 6.7 to 109.7; p =
      0.001) and mechanical ventilation (OR, 3.3; 95% CI, 1.02 to 10.9; p = 0.04).
      Transplantation was associated with a lower risk of A terreus infection (OR, 0.2;
      95% CI, 0.046 to 0.789; p = 0.02). CONCLUSIONS: In patients with culture findings
      positive for filamentous fungi, the prophylactic use of amphotericin B aerosols
      and mechanical ventilation are associated with a higher risk of A terreus
      infections. In these patients, transplantation is associated with a lower risk of
      isolation and respiratory infection by A terreus.

PMID- 17218582
TI  - Comparison of total-breath and single-breath diffusing capacity in healthy
      volunteers and COPD patients.
AB  - BACKGROUND: The measurement of single-breath diffusing capacity (Dlco(SB))
      assumes that diffusing capacity per liter of alveolar volume (Dlco/VA) determined
      in a 750-mL gas sample represents the diffusing capacity (Dlco) of the entire
      lung. Fast-responding gas analyzers provide the opportunity to verify this
      assumption because of the possibility to measure CO and CH(4) fractions
      continuously throughout the entire expiration. Continuous gas sampling provides
      more information per measurement, but this information cannot be expressed in the
      traditional parameters. Our goals were to find new parameters to express the
      extra information of the continuous gas sampling, and to compare these new
      parameters with the traditional parameters. METHODS: We compared a new method to
      determine Dlco with the traditional method in 62 healthy volunteers and 26 COPD
      patients. Traditionally, Dlco(SB) is determined by multiplying Dlco/VA with
      alveolar volume, both calculated from gas concentrations in a 750-mL gas sample.
      The new method calculates total-breath Dlco (Dlco(TB)) by integration of Dlco/VA
      against exhaled volume. RESULTS: In healthy volunteers, Dlco/VA shows a slight
      upward slope during exhalation, while in COPD patients Dlco/VA shows a horizontal
      line. Total-breath total lung capacity (TLC) is larger than single-breath TLC
      both in healthy volunteers and in COPD patients, leading to a Dlco(TB) that is
      significantly larger than Dlco(SB) in both groups (p < 0.001). CONCLUSION: The
      assumption that a 750-mL gas sample represents the entire lung seems to be
      correct for Dlco/VA but not for the CH(4) fraction in case of ventilation
      inhomogeneity.

PMID- 17218583
TI  - Lung function and farm size predict healthy worker effect in swine farmers.
AB  - BACKGROUND: Swine farmers are exposed to a number of airborne contaminants
      associated with respiratory ill health. OBJECTIVES: To examine the factors
      associated with healthy worker effect in the swine industry from a longitudinal
      follow-up of farmers at 4 years and 13 years. DESIGN: A prospective study of
      swine farmers and nonexposed rural residents was conducted using similar
      questionnaires and same spirometer at each time point. RESULTS: In the original
      observations in 1990/1991, we studied 302 swine farmers and 261 nonfarming
      control subjects. Four years later in 1994/1995, 217 swine farmers and 171
      nonfarming control subjects of the original group participated again. In
      2003/2004, 163 swine farmers and 118 control subjects were retested. Of the 163
      swine farmers, 52 remained active swine farmers and 111 were no longer swine
      farming, thus providing the opportunity to evaluate work continuity in the
      industry. Among farmers studied in 2003/2004, mean values for percentage of
      predicted FEV(1)/FVC ratio and forced expiratory flow between 25% and 75% of FVC
      were lower in those who had quit swine farming compared to those still swine
      farming and nonfarming control subjects. The herd size in the barn at baseline in
      1990/1991 and at interim follow-up in 1994/1995 was a significant predictor of
      quitting swine farming. In addition, percentage of predicted FEV(1)/FVC at the
      interim observation was a significant predictor of quitting swine farming.
      CONCLUSIONS: There is a significant healthy worker effect among swine farmers.
      The continuation of work in the facilities may be predicted by herd size and
      interim lung function.

PMID- 17218585
TI  - State of the art: interventional pulmonology.
AB  - Interventional pulmonology (IP) provides comprehensive care to patients with
      structural airway disorders and pleural diseases. A growing armamentarium of
      diagnostic and therapeutic tools has expanded the interventional pulmonologist's
      ability to care for pulmonary patients with complex abnormalities, often in
      concert and close collaboration with physicians in other specialties, such as
      thoracic surgery. Innovative technologies promise to have an impact on diseases
      and clinical entities not traditionally treated by invasive pulmonary
      interventions, such as asthma, COPD, and the solitary pulmonary nodule. Training,
      credentialing, reimbursement, and scientific validation remain key necessities
      for the continued growth of IP, and require a concerted effort by chest
      physicians and their professional organizations.

PMID- 17218584
TI  - The utility of fluorodeoxyglucose positron emission tomography in the evaluation
      of carcinoid tumors presenting as pulmonary nodules.
AB  - BACKGROUND: Fluorodeoxyglucose positron emission tomography (FDG-PET) is
      sensitive for detection of neoplastic solitary pulmonary nodules but may have
      decreased sensitivity for detection of carcinoid tumors. Our purpose was to
      determine the sensitivity of FDG-PET to detect pulmonary carcinoid tumors.
      METHODS: We performed a retrospective review of our institutional results
      regarding FDG-PET in the setting of thoracic carcinoid neoplasms. We identified
      16 patients with a pathologic diagnosis of bronchial carcinoid who had an
      antecedent FDG-PET (from 2000 to 2004). All patients but one presented with
      pulmonary nodule(s). RESULTS: Sixteen patients had a diagnosis of carcinoid
      tumor, typical in 11 patients and atypical in 5 patients. The mean greatest
      pathologic dimension was 2.08 cm (range, 1.0 to 8.3 cm). Overall positron
      emission tomography (PET) sensitivity was 75% (12 true-positive and 4 false
      negative results). The mean (+/- SD) size of carcinoids with false-negative PET
      results was not significantly different from carcinoids with true-positive
      results (1.6 +/- 0.81 cm and 2.35 +/- 1.87 cm, p = 0.54). Fifteen of 16 patients
      were staged pathologically, and positive nodes were found in 2 of these patients.
      PET lymph node staging agreed with pathologic staging in one stage 4 patient with
      positive lymph nodes and distant metastasis, but PET results were false negative
      in the other patient who had N2 with micrometastatic disease; stage IIIA.
      CONCLUSIONS: FDG-PET imaging is useful for evaluation of typical and atypical
      thoracic carcinoid tumors. Although overall PET sensitivity for detection of
      carcinoid tumors is somewhat reduced as compared to non-small cell lung cancer,
      it is much higher than prior reports suggest.

PMID- 17218586
TI  - Risk of thrombosis with lenalidomide and its prevention with aspirin.
AB  - Lenalidomide, an analog of thalidomide, is an effective new treatment for
      multiple myeloma. Both compounds are associated with an increased risk of venous
      thromboembolism, particularly when used in combination with high-dose
      dexamethasone. As new trials with lenalidomide are being planned and performed,
      investigators are placing high importance on reducing the risk of thrombosis by
      incorporating an antithrombotic agent into the therapeutic regimen. Low-molecular
      weight heparin, warfarin, and aspirin have all been suggested as candidate drugs
      for thromboprophylaxis, but none of these agents have been evaluated in
      randomized clinical trials. A body of opinion has evolved that aspirin is very
      effective in preventing venous thrombosis in myeloma patients treated with
      lenalidomide. If correct, this view has important implications, because aspirin
      is inexpensive and is safer and more convenient than anticoagulants. On the other
      hand, aspirin is less effective than anticoagulants for preventing venous
      thrombosis in other high-risk groups, and therefore might not be the most
      appropriate choice for preventing of venous thrombosis in myeloma patients. This
      commentary examines the strength of the evidence supporting the effectiveness of
      aspirin in preventing venous thrombosis in multiple myeloma patients treated with
      lenalidomide. It is concluded that the evidence that aspirin is efficacious in
      preventing venous thrombosis in myeloma patients is based on "before/after" and
      retrospective studies, with potential for bias and confounders. There is,
      therefore, a critical need to incorporate a randomized comparison of aspirin with
      an anticoagulant in future trials evaluating lenalidomide in multiple myeloma.

PMID- 17218587
TI  - A systematic review of randomized controlled trials examining the short-term
      benefit of ambulatory oxygen in COPD.
AB  - AIM: To systematically review the short-term efficacy of ambulatory oxygen from
      single-assessment studies in COPD. METHODS: Searches for relevant randomized
      controlled trials using predefined search terms were conducted on the Cochrane
      Airways Group Specialized Register of RCTs, the Cochrane Central Register of
      Controlled Trials, and other electronically available journals, databases, and
      search engines. All databases were searched from their inception until December
      2004. Two reviewers (J.B., B.O.) independently assessed eligibility and extracted
      data. All trial data were combined using RevMan analyses 4.2.8 (Cochrane
      Collaboration; www.cochrane.org). Due to the crossover design of the studies,
      data were entered using the generic inverse variance method. Fixed-effect or
      random-effect models were used depending on the level of statistical
      heterogeneity observed. RESULTS: Thirty-one studies (33 data sets; 534
      participants) met the inclusion criteria of the review. Oxygen improved the
      primary outcomes relating to endurance and maximal exercise capacity. For the
      secondary outcomes of breathlessness, arterial oxygen saturation (Sao(2)), and
      minute ventilation (Ve), comparisons were made at isotime. Oxygen improved
      breathlessness, Sao(2)/Pao(2), and Ve at isotime with endurance exercise testing.
      For maximal exercise testing, data were not available in a format suitable for
      metaanalysis for breathlessness, but the improvement in Sao(2)/Pao(2) and Ve at
      isotime was significant. CONCLUSION: This review provides evidence from single
      assessment studies that ambulatory oxygen improves exercise performance in COPD;
      however, the clinical importance of this size of improvement is unclear. Prior to
      widespread prescription of ambulatory oxygen, future research is required to
      establish the net long-term benefit of ambulatory oxygen in patients with
      different levels of hypoxemia or exercise-induced desaturation.

PMID- 17218588
TI  - Continuous bronchodilator therapy.
AB  - Inhaled bronchodilators are first-line treatment for acute exacerbations of
      asthma. Continuous bronchodilator administration is a novel option for the
      treatment of bronchospasm, which may be more effective than intermittent therapy
      for patients with severe airflow obstruction. For 2007, coding and billing
      changes for this modality become effective. This article reviews clinical aspects
      and outpatient practice management of continuous bronchodilator therapy.

PMID- 17218589
TI  - Small cell lung cancer presenting as a paraneoplastic syndrome characterized by
      recurrent episodic hypotension and bradycardia: case report.
AB  - A 56-year-old man presenting with a 6-month history of recurrent episodic
      hypotension and bradycardia was found to have limited-stage small cell lung
      cancer. During both quiescence and episodes of hemodynamic embarrassment,
      extensive evaluations were conducted. Possible explanations included the
      following: intermittent great vessel obstruction; baroreceptor
      failure/hypersensitivity; and autonomic dysfunction. His clinical course favored
      an antibody-negative dysautonomic paraneoplastic syndrome.

PMID- 17218590
TI  - A localized pleural based mass with intense uptake on positron emission
      tomography scan.

PMID- 17218591
TI  - Prevention of acute renal failure.
AB  - Acute renal failure (ARF) comprises a family of syndromes that is characterized
      by an abrupt and sustained decrease in the glomerular filtration rate. In the
      ICU, ARF is most often due to sepsis and other systemic inflammatory states. ARF
      is common among the critically ill and injured and significantly adds to
      morbidity and mortality of these patients. Despite many advances in medical
      technology, the mortality and morbidity of ARF in the ICU continue to remain high
      and have not improved significantly over the past 2 decades. Primary strategies
      to prevent ARF still include adequate hydration, maintenance of mean arterial
      pressure, and minimizing nephrotoxin exposure. Diuretics and dopamine have been
      shown to be ineffective in the prevention of ARF or improving outcomes once ARF
      occurs. Increasing insight into mechanisms leading to ARF and the importance of
      facilitating renal recovery has prompted investigators to evaluate the role of
      newer therapeutic agents in the prevention of ARF.

PMID- 17218592
TI  - A 20-year-old man with status epilepticus and uncontrolled hypertension.

PMID- 17218593
TI  - A 58-year-old man with episodically widened pulse pressure.

PMID- 17218594
TI  - Documenting research in scientific articles: guidelines for authors: 2. Reporting
      hypothesis tests.

PMID- 17218595
TI  - Managing a rare condition presenting with intractable hypoxemic respiratory
      failure.

PMID- 17218596
TI  - Real-time electromagnetic navigation bronchoscopy for peripheral lesions: what
      about the negative predictive value?

PMID- 17218597
TI  - Notice from the editor-in-chief and the ethics subcommittee of CHEST associate
      editors.

PMID- 17218598
TI  - Role for transbronchial biopsy in the diagnosis of usual interstitial pneumonia.

PMID- 17218599
TI  - Allergic rhinitis may be important in snoring infants.

PMID- 17218600
TI  - Deficiency of Niemann-Pick C1 Like 1 prevents atherosclerosis in ApoE-/- mice.
AB  - OBJECTIVE: The objective of this study was to determine whether the deficiency of
      Niemann-Pick C1 Like 1 (Npc1l1) prevents atherosclerosis in apoE null mice.
      METHODS AND RESULTS: Npc1l1(-/-)/apoE null-/- mice were generated and found to
      have a significant reduction in cholesterol absorption (-77%) compared with wild
      type or apoE-/- mice. Npc1l1/apoE-/- mice were fed a chow or Western diet for 24
      weeks, then lipoprotein, hepatic, and biliary cholesterol, and atherosclerosis
      development was compared with apoE-/-, Npc1l1-/-, wild-type, and ezetimibe
      treated apoE-/- mice. Chylomicron remnant/VLDL cholesterol levels were reduced
      80% to 90% in both chow and Western diet-fed Npc1l1/apoE-/- mice relative to apoE
      /- mice. Male Npc1l1-/- and Npc1l1/apoE-/- mice were completely resistant to diet
      induced hypercholesterolemia, and both male and female mice were completely
      resistant to increases in hepatic and biliary cholesterol levels. Atherosclerosis
      was reduced 99% in aortic lesion surface area, 94% to 97% in innominate artery
      intimal lesion area, and >90% in aortic root lesion area in both male and female
      Npc1l1/apoE-/- mice relative to apoE-/- mice. CONCLUSIONS: Lack of Npc1l1, the
      molecular target of the cholesterol absorption inhibitor ezetimibe, in apoE-/-
      mice results in a significant reduction in cholesterol absorption and plasma
      cholesterol levels, and causes a nearly complete protection from the development
      of atherosclerosis, under both cholesterol-fed and non-cholesterol-fed
      conditions.

PMID- 17218601
TI  - Role of oxidative stress in the pathogenesis of abdominal aortic aneurysms.
AB  - The role of inflammation in the pathogenesis of abdominal aortic aneurysms (AAA)
      is well established. The inflammatory process leads to protease-mediated
      degradation of the extracellular matrix and apoptosis of smooth muscle cells
      (SMC), which are the predominant matrix synthesizing cells of the vascular wall.
      These processes act in concert to progressively weaken the aortic wall, resulting
      in dilatation and aneurysm formation. Oxidative stress is invariably increased
      in, and contributes importantly to, the pathophysiology of inflammation.
      Moreover, reactive oxygen species (ROS) play a key role in regulation of matrix
      metalloproteinases and induction of SMC apoptosis. ROS may also contribute to the
      pathogenesis of hypertension, a risk factor for AAA. Emerging evidence suggests
      that ROS and reactive nitrogen species (RNS) are associated with AAA formation in
      animal models and in humans. Although experimental data are limited, several
      studies suggest that modulation of ROS production or activity may suppress AAA
      formation and improve experimental outcome in rodent models. Although a number of
      enzymes can produce injurious ROS in the vasculature, increasing evidence points
      toward a role for NADPH oxidase as a source of oxidative stress in the
      pathogenesis of AAA.

PMID- 17218602
TI  - Ca2+ and inositol 1,4,5-trisphosphate-mediated signaling across the
      myoendothelial junction.
AB  - Second messenger signaling between endothelial cells (ECs) and vascular smooth
      muscle cells (VSMCs) is poorly understood, but intracellular Ca2+ concentrations
      ([Ca2+]i) in the 2 cells are coordinated, possibly through gap junctions at the
      myoendothelial junction. To study heterocellular calcium signaling, we used a
      vascular cell coculture model composed of monolayers of ECs and VSMCs.
      Stimulation of either cell type leads to an increase in [Ca2+]i in the stimulated
      cell and a secondary increase in [Ca2+]i in the other cell type that was blocked
      by gap junction inhibitors. To determine which second messengers are involved, we
      initially depleted Ca2+ stores in the endoplasmic reticulum Ca2+ with
      thapsigargin in ECs or VSMCs, but this had no effect on heterocellular calcium
      signaling. Alternatively, we loaded ECs or VSMCs with 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) to buffer changes in
      [Ca2+]i. BAPTA loading of ECs inhibited agonist-induced increases in
      intracellular calcium concentration ([Ca2+]i), in both ECs and VSMCs. In
      contrast, BAPTA loading of the VSMCs blunted the VSMC response but did not alter
      the secondary increase in EC [Ca2+]i. Xestospongin C (an inositol 1,4,5
      trisphosphate receptor inhibitor) had no effect on the secondary Ca2+ response,
      but when xestospongin C or thapsigargin was loaded into ECs and BAPTA into VSMCs,
      intercellular Ca2+ signaling was completely blocked. We conclude that 1,4,5
      trisphosphate and Ca2+ originating in the VSMCs induces the secondary increase in
      EC [Ca2+]i but stimulation of the ECs generates a Ca2+ dependent response in the
      VSMCs.

PMID- 17218603
TI  - The bone morphogenetic protein antagonist noggin regulates mammalian cardiac
      morphogenesis.
AB  - Bone morphogenetic proteins (BMPs) play many roles in mammalian cardiac
      development. Here we address the functions of Noggin, a dedicated BMP antagonist,
      in the developing mouse heart. In early cardiac tissues, the Noggin gene is
      mainly expressed in the myocardial cells of the outflow tract, atrioventricular
      canal, and future right ventricle. The major heart phenotypes of Noggin mutant
      embryos are thicker myocardium and larger endocardial cushions. Both defects
      result from increased cell number. Cell proliferation is increased and cell cycle
      exit is decreased in the myocardium. Although we find evidence of increased BMP
      signal transduction in the myocardium and endocardium, we show that the cardiac
      defects of Noggin mutants are rescued by halving the gene dosage of Bmp4. In
      culture, BMP increases the epithelial-to-mesenchymal transformation (EMT) of
      endocardial explant cells. Increased EMT likely accounts for the enlarged
      atrioventricular cushion. In the outflow tract cushion, we observed an increased
      contribution of cardiac neural crest cells to the mutant cushion mesenchyme,
      although many cells of the cushion were not derived from neural crest. Thus the
      enlarged outflow tract cushion of Noggin mutants likely arises by increased
      contributions both of endocardial cells that have undergone EMT as well as cells
      that have migrated from the neural crest. These data indicate that antagonism of
      BMP signaling by Noggin plays a critical role in ensuring proper levels of cell
      proliferation and EMT during cardiac morphogenesis in the mouse.

PMID- 17218604
TI  - Capillary perfusion and wall shear stress are restored in the coronary
      circulation of hypertrophic right ventricle.
AB  - It has been shown that right ventricle (RV) hypertrophy involves significant
      compensatory vascular growth and remodeling. The objective of the present study
      was to determine the functional implications of the vascular growth and
      remodeling through a full flow analysis of arterial tree down to first capillary
      segments. A computer reconstruction of RV branches including the proximal right
      coronary artery to the posterior descending artery was established based on
      measured morphometric data in arrested, vasodilated porcine heart. The flows were
      computed throughout the reconstructed trees based on conservation of mass and
      momentum and appropriate pressure boundary conditions. It was found that the flow
      rate was significantly increased in large epicardial coronary arteries in
      hypertrophic as compared with control hearts but normalized in the
      intramyocardial coronary arteries and smaller vessels in RV hypertrophy primarily
      because of the significant increase in number of arterioles. Furthermore, the
      wall shear stress was restored to nearly homeostatic levels throughout most of
      the vasculature after 5 weeks of RV hypertrophy. The compensatory remodeling in
      RV hypertrophy functionally restores the perfusion at the arteriolar and
      capillary level and wall shear stress in most of larger vessels. This is the
      first full analysis of coronary arterial tree, with millions of vessels, in
      cardiac hypertrophy that reveals the compensatory adaptation of structure to
      function.

PMID- 17218605
TI  - Tissue engineering of vascularized cardiac muscle from human embryonic stem
      cells.
AB  - Transplantation of a tissue-engineered heart muscle represents a novel
      experimental therapeutic paradigm for myocardial diseases. However, this strategy
      has been hampered by the lack of sources for human cardiomyocytes and by the
      scarce vasculature in the ischemic area limiting the engraftment and survival of
      the transplanted muscle. Beyond the necessity of endothelial capillaries for the
      delivery of oxygen and nutrients to the grafted muscle tissue, interactions
      between endothelial and cardiomyocyte cells may also play a key role in promoting
      cell survival and proliferation. In the present study, we describe the formation
      of synchronously contracting engineered human cardiac tissue derived from human
      embryonic stem cells containing endothelial vessel networks. The 3D muscle
      consisted of cardiomyocytes, endothelial cells (ECs), and embryonic fibroblasts
      (EmFs). The formed vessels were further stabilized by the presence of mural cells
      originating from the EmFs. The presence of EmFs decreased EC death and increased
      EC proliferation. Moreover, the presence of endothelial capillaries augmented
      cardiomyocyte proliferation and did not hamper cardiomyocyte orientation and
      alignment. Immunostaining, ultrastructural analysis (using transmission electron
      microscopy), RT-PCR, pharmacological, and confocal laser calcium imaging studies
      demonstrated the presence of cardiac-specific molecular, ultrastructural, and
      functional properties of the generated tissue constructs with synchronous
      activity mediated by action potential propagation through gap junctions. In
      summary, this is the first report of the construction of 3D vascularized human
      cardiac tissue that may have unique applications for studies of cardiac
      development, function, and tissue replacement therapy.

PMID- 17218606
TI  - High-mobility group box 1 activates integrin-dependent homing of endothelial
      progenitor cells.
AB  - Endothelial progenitor cells (EPCs) are recruited to ischemic regions and improve
      neovascularization. Integrins contribute to EPC homing. High-mobility group box 1
      (HMGB1) is a nuclear protein that is released extracellularly on cell necrosis
      and tissue damage, eliciting a proinflammatory response and stimulating tissue
      repair. In the present study, we investigated the effects of HMGB1 on EPC homing.
      EPCs express the HMGB1 receptors RAGE (receptor for advanced glycation end
      products) and TLR2 (Toll-like receptor 2). EPC migration was stimulated by HMGB1
      in a RAGE-dependent manner. In addition, the HMGB1-induced migration of EPCs on
      fibronectin and fibrinogen was significantly inhibited by antibodies against
      beta1 and beta2 integrins, respectively. Short-term prestimulation of EPCs with
      HMGB1 also increased EPC adhesion to endothelial cell monolayers, and this effect
      was blocked by antibodies to beta2 integrins or RAGE. HMGB1 increased EPC
      adhesion to the immobilized integrin ligands intercellular adhesion molecule-1
      and fibronectin in a RAGE-dependent manner. Strikingly, HMGB1 rapidly increased
      integrin affinity and induced integrin polarization. Using intravital microscopy
      in a tumor model of neovascularization, prestimulation of EPCs with HMGB1
      enhanced the initial in vivo adhesion of EPCs to microvessels and the recruitment
      of EPCs in the tumor tissue. In addition, prestimulation of EPCs with HMGB1
      increased the homing of EPCs to ischemic muscles. In conclusion, these data
      represent a link between HMGB1 and integrin functions of EPCs and demonstrate
      that HMGB1 stimulates EPC homing to ischemic tissues. These results may provide a
      platform for the development of novel therapeutic approaches to improve EPC
      homing.

PMID- 17218607
TI  - Fluid shear stress and NO decrease the activity of the hydroxy-methylglutaryl
      coenzyme A reductase in endothelial cells via the AMP-activated protein kinase
      and FoxO1.
AB  - The rate-limiting enzyme for cholesterol synthesis, the hydroxy-methylglutaryl
      coenzyme A reductase (HCR), is phosphorylated by the AMP-activated protein kinase
      (AMPK). As shear stress activates the AMPK in endothelial cells, we determined
      whether it affects HCR activity and subsequent HCR-dependent signaling. Shear
      stress (12 dynes cm(-2)) rapidly increased the phosphorylation and activity (6.5-
      and 4-fold, respectively) of the AMPK in cultured endothelial cells and the
      activated AMPK phosphorylated the HCR in vitro. Moreover, shear stress and the
      AMPK activator 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) attenuated
      endothelial HCR activity by 37% and 33%, respectively. Inhibition of NO
      production attenuated the acute shear stress-induced phosphorylation of the AMPK
      and the decrease in HCR activity. Prolonged shear stress (18 hours) led to a
      significant (50%) decrease in HCR mRNA expression that was dependent on NO, AMPK,
      and the subsequent phosphorylation and degradation of FoxO1a. Correspondingly,
      the downregulation of FoxO (small interfering RNA) decreased HCR expression.
      Prolonged shear stress also attenuated the bradykinin-induced activation of Ras
      and extracellular signal-regulated kinase 1/2, a phenomenon that was comparable
      to the effects of cerivastatin and that was reversed by mevalonate and thus
      attributed to HCR inhibition. A decrease (35%) in HCR expression was also
      detected in femoral arteries from mice following voluntary exercise, and the
      bradykinin-induced vasodilatation of the mouse hindlimb was attenuated by both
      exercise and the HCR inhibitor cerivastatin. These data indicate that fluid shear
      stress regulates the activity and expression of the HCR in endothelial cells and
      determines responsiveness to stimuli, such as bradykinin via a mechanism
      involving NO, AMPK, FoxO1a, and p21Ras.

PMID- 17218608
TI  - Infant growth and stroke in adult life: the Helsinki birth cohort study.
AB  - BACKGROUND AND PURPOSE: People who had low birth weight are at increased risk of
      stroke. Little is known about the effects of early postnatal growth on stroke
      risk. METHODS: We followed-up 12 439 people born in Helsinki during 1934 to 1944.
      Their body size was measured at birth and, on average, 9 times between birth and
      age 2 years; 507 of them were hospitalized with stroke or died from the disease.
      RESULTS: Hazard ratios for stroke declined progressively with increasing gain in
      weight between birth and age 2 years. The hazard ratio was 0.85 (95% CI, 0.78 to
      0.93; P=0.0004) per standard deviation increase in the difference between the
      weight attained at age 2 years and that predicted from birth weight. A 1-standard
      deviation increase in body mass index at 2 years of age was associated with a
      hazard ratio for stroke of 0.84 (95% CI, 0.77 to 0.92; P=0.0002). This
      association was little changed by adjustment for measures of socio-economic
      status. Change in body size after the age of 2 years had little effect on the
      risk of later stroke. People whose mothers had a small external conjugate
      diameter of the pelvis had an increased risk of stroke. The hazard ratio
      associated with a diameter of < or =18 cm was 1.62 (95% CI, 1.30 to 2.02;
      P<0.0001). CONCLUSIONS: Thinness during infancy is associated with an increased
      risk of stroke in later life. This association may be the result of maternal
      influences which originated in the mother's infancy when her pelvic shape was
      established.

PMID- 17218609
TI  - Noninvasive evaluation of dynamic cerebrovascular autoregulation using Finapres
      plethysmograph and transcranial Doppler.
AB  - BACKGROUND AND PURPOSE: Mx is an index of cerebrovascular autoregulation. It is
      calculated as the correlation coefficient between slow spontaneous fluctuations
      of cerebral perfusion pressure (cerebral perfusion pressure=arterial blood
      pressure-intracranial pressure) and cerebral blood flow velocity. Mx can be
      estimated noninvasively (nMxa) with the use of a finger plethysmograph arterial
      blood pressure measurement instead of an invasive cerebral perfusion pressure
      measurement. We investigated the agreement between nMxa and the previously
      validated index Mx. METHODS: The study included 10 head-injured adults.
      Intracranial pressure was monitored with a parenchymal probe. Arterial blood
      pressure was monitored simultaneously with an arterial catheter and with the
      Finapres plethysmograph. Flow velocity in the middle cerebral artery was measured
      bilaterally with transcranial Doppler. Mx and nMxa were computed in both
      hemispheres, and asymmetry of autoregulation was calculated. RESULTS: Ninety-six
      measures of Mx and nMxa were obtained (48 for each side) in 10 patients. Mx
      correlated with nMxa (R=0.755, P<0.001; 95% agreement=+/-0.36; bias=0.01).
      Asymmetry in autoregulation assessed with Mx correlated significantly with
      asymmetry estimated with nMxa (R=0.857, P<0.0001; 95% agreement=+/-0.26; bias=
      0.03). CONCLUSIONS: The noninvasive index of autoregulation nMxa correlates with
      Mx and is sensitive enough to detect autoregulation asymmetry. nMxa is proposed
      as a practical tool to assess cerebral autoregulation in patients who do not
      require invasive monitoring.

PMID- 17218610
TI  - Cardiac autonomic nervous system and risk of arrhythmias in cerebral autosomal
      dominant arteriopathy with subcortical infarcts and leukoencephalopathy
      (CADASIL).
AB  - BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical
      infarcts and leukoencephalopathy (CADASIL) is an inherited systemic
      microangiopathy with prevalently cerebral manifestations. Among the causes of
      death, sudden unexpected death seems to occur in a significant number of CADASIL
      patients. Because potential causes of sudden unexpected death may include cardiac
      arrhythmias and myocardial infarction, we evaluated risk factors for life
      threatening arrhythmias, such as reduced heart rate variability, sympathetic
      overactivity and QT interval (QTc) prolongation, in 23 CADASIL patients. The
      relationship of these changes with brain MRI pattern was also investigated.
      METHODS: Frequency domain measures of heart rate variability (10 minutes
      recordings) and QTc interval were recorded in 23 CADASIL patients (17 males, 6
      females) and 22 healthy age- and sex-matched control subjects. The following
      heart rate variability spectral parameters were considered at rest during
      spontaneous and controlled breathing (Cb): total power, very-low-frequency
      component, low-frequency component, high-frequency component, low-frequency/high
      frequency ratio, and Cb-total power, Cb-very-low-frequency component, Cb-low
      frequency component, Cb-high-frequency component, Cb-low-frequency/high-frequency
      ratio. R-to-R wave and QTc interval were also analyzed. All data were
      statistically compared between CADASIL and control subjects. Conventional brain
      MRI was performed in patients with CADASIL and T1-weighted and T2-weighted lesion
      volumes, and were compared with each spectral component of the tachogram.
      RESULTS: During spontaneous and controlled breathing, total power spectrum and
      all spectral components (very low frequency component, high-frequency component,
      low-frequency component) of heart rate variability were significantly reduced in
      CADASIL patients with respect to controls (P<0.05). The low-frequency/high
      frequency component ratio was significantly higher in CADASIL patients than in
      controls. No significant correlation between heart rate variability spectral
      parameters and other variables including total brain T2-weighted and T1-weighted
      lesion volumes were observed in CADASIL subjects. CONCLUSIONS: We found a
      statistically significant reduction in all frequency domain parameters of heart
      rate variability associated with a higher low frequency/high frequency ratio for
      CADASIL patients with respect to normal subjects. These data are consistent with
      autonomic derangement and suggests that CADASIL patients may be at risk for life
      threatening arrhythmias. This could at least in part explain their higher
      recurrence of sudden unexpected death and should be taken into account in
      planning therapy.

PMID- 17218611
TI  - Baseline disease activity, hyperlipidemia, and hypertension are predictive
      factors for ischemic stroke and stroke severity in systemic lupus erythematosus.
AB  - BACKGROUND AND PURPOSE: To determine factors associated with ischemic stroke and
      stroke severity in patients with systemic lupus erythematosus. METHODS: Between
      1992 and January 2005, 238 consecutive systemic lupus erythematosus patients with
      no history of stroke were followed-up longitudinally at the Maryland Lupus
      Clinic. Patients were monitored quarterly for a mean of 8 years after their
      systemic lupus erythematosus diagnosis, and 44 patients (19%) developed first
      ever ischemic stroke. At the end of study, Cox proportional regression analyses
      were used to determine the effect of baseline clinical variables of systemic
      lupus erythematosus patients in relation to the subsequent occurrence of ischemic
      stroke and stroke severity after first-ever ischemic strokes. Severe stroke was
      defined as having a National Institute of Health Stroke Scale > or =6. RESULTS:
      Severe ischemic strokes occurred in 34 of 44 (77%) patients. Baseline predictors
      of ischemic strokes and severe ischemic strokes included disease activity,
      hyperlipidemia, and hypertension. CONCLUSIONS: Severe ischemic strokes in
      systemic lupus erythematosus are not uncommon. Aggressive primary and secondary
      stroke prevention measures, particularly treatment of hyperlipidemia and
      hypertension, as well as vigorous treatment of clinical symptoms of active lupus,
      are needed to prevent serious morbidity and neurological disability.

PMID- 17218612
TI  - Effects of toxoplasma on human behavior.
AB  - Although latent infection with Toxoplasma gondii is among the most prevalent of
      human infections, it has been generally assumed that, except for congenital
      transmission, it is asymptomatic. The demonstration that latent Toxoplasma
      infections can alter behavior in rodents has led to a reconsideration of this
      assumption. When infected human adults were compared with uninfected adults on
      personality questionnaires or on a panel of behavioral tests, several differences
      were found. Other studies have demonstrated reduced psychomotor performance in
      affected individuals. Possible mechanisms by which T. gondii may affect human
      behavior include its effect on dopamine and on testosterone.

PMID- 17218613
TI  - The effect of Toxoplasma gondii on animal behavior: playing cat and mouse.
AB  - A convincing body of evidence now exists to indicate that the ubiquitous
      protozoan Toxoplasma gondii can cause permanent behavioral changes in its host,
      even as a consequence of adult-acquired latent infection. Such behavioral
      alterations appear to be the product of strong selective pressures for the
      parasite to enhance transmission from its intermediate host reservoir, primarily
      rodent, to its feline definitive host, wherein sexual reproduction can occur and
      the life cycle completed. This article reviews evidence of behavioral alterations
      in animal hosts and considers what these may elucidate about the potential
      mechanisms involved and what implications such alterations could have on animal
      and human health.

PMID- 17218615
TI  - Prolonged inhaled allergen exposure can induce persistent tolerance.
AB  - Murine asthma models suggest that failure of immune tolerance rather than a
      defective T helper cell type 1 (Th1) immunity underlies the immune biology of Th2
      driven allergen-induced airway disease. Intriguingly, prolonged exposures can
      result in a full waning of inflammation. The mechanisms underlying this
      observation are not understood. We hypothesized that the fading of inflammation
      is the result of regulatory processes, characterized by altered dendritic cell
      (DC)-T cell interactions. First, we implemented a model in which mice developed
      Th2-driven airway disease. When we subjected these mice to prolonged antigen
      ovalbumin (OVA) exposures (8 wk), all inflammation disappeared. Re-immunization
      and re-challenge showed an inability to mount Th2-skewed immune responses, with
      absence of airway eosinophils, IgE, and Th2 cytokines. Besides specific immune
      tolerance, bystander protection was observed. A decrease in CD4+CD25+Foxp3+ T
      regulatory cells, PD-1, and IL-10 expression was discerned as compared with acute
      inflammation. In addition, suppression of ICOS and CD28 was found, along with
      inhibited DC maturation. This process of disease inhibition surprisingly had a
      long-lasting memory and was not caused by endotoxin signaling through TLR-4. In
      summary, our results indicate that the disappearance of Th2-driven airway disease
      upon persistent antigen exposure is associated with the induction of immune
      tolerance. The tolerant state is antigen-dependent, and extends to bystander
      antigens. Moreover, this tolerance is characterized by an altered DC-T cell
      communication and is long-lasting. Our data further suggest that the mechanism of
      the disease inhibition after allergic airway inflammation differs from the anti
      inflammatory mechanisms observed during acute eosinophilic airway inflammation.

PMID- 17218614
TI  - Regulation of eosinophil adhesion by lysophosphatidylcholine via a non-store
      operated Ca2+ channel.
AB  - We examined the mechanism by which lysophosphatidylcholine (LPC) regulates beta2
      integrin-mediated adhesion of eosiniophils. Eosinophils were isolated from blood
      of mildly atopic volunteers by negative immunomagnetic selection. beta2-integrin
      dependent adhesion of eosinophils to plated bovine serum albumin (BSA) was
      measured by residual eosinophil peroxidase activity. LPC caused maximal adhesion
      of eosinophils to plated BSA at 4 microM. Lysophosphatidylinositol, which has a
      similar molecular shape, mimicked the effect of LPC on eosinophil adhesion, while
      neither lysophosphatidylserine nor lysophosphatidylethanolamine had any effect.
      Phosphatidylethanolamine, a lipid that has a molecular orientation that is the
      inverse of LPC, blocked eosinophil adhesion caused by LPC. Unlike platelet
      activating factor, a G-protein-coupled receptor agonist, LPC did not cause Ca2+
      store depletion, but caused increased Ca2+ influx upon addition of Ca2+ to
      extracellular medium. This influx was not inhibited by U73122, a phospholipase C
      inhibitor, demonstrating independence from the G protein-activated phospholipase
      C pathway. Ca2+ influx was inhibited by either preincubation of
      phosphotidylethanolamine or La3+, a broad spectrum blocker of cation channels.
      LPC induced up-regulation of the active conformation of CD11b, which was blocked
      by preincubation with phosphatidylethanolamine. These data suggest that LPC
      causes a non-store-operated Ca2+ influx into eosinophils, which subsequently
      activates CD11b/CD18 to promote eosinophil adhesion.

PMID- 17218617
TI  - Prediction of cellular immune responses against CFTR in patients with cystic
      fibrosis after gene therapy.
AB  - Different classes of mutations (class I-VI) of the cystic fibrosis (CF)
      transmembrane conductance regulator (CFTR) gene are responsible for
      lung/pancreatic disease. The most common mutation, DeltaF508, is characterized by
      expression of precursor forms of CFTR but no functional CFTR. Since only 5-10% of
      normal CFTR function is required to correct the electrophysiologic defect across
      the airway epithelium, gene therapy holds promise for treatment of patients with
      CF lung disease. However, efficient delivery and transgene expression are not the
      only parameters that may influence the success of gene therapy. Host-specific
      immune responses generated against the therapeutic CFTR protein may pose a
      problem, especially when the coding sequence between the normal CFTR and mutated
      CFTR differ. This phenomenon is more pertinent to class I mutations in which
      large fragments of the protein are not expressed. However, T cells directed
      against epitopes that span sequences containing class II-V mutations are also
      possible. We used MHC-binding prediction programs to predict the probability of
      cellular immune responses that may be generated against CFTR in DeltaF508
      homozygote patients. Results obtained from running the prediction algorithms
      yielded a few high-scoring MHC-Class I binders within the specific sequences,
      suggesting that there is a possibility of the host to mount a cellular immune
      response against CFTR, even when the difference between therapeutic and host CFTR
      is a single amino acid (F) at position 508.

PMID- 17218616
TI  - Oxidative-nitrosative stress and post-translational protein modifications:
      implications to lung structure-function relations. Arginase modulates NF-kappaB
      activity via a nitric oxide-dependent mechanism.
AB  - NF-kappaB is a versatile transcription factor that regulates a wide array of
      processes, including inflammation and survival, and plays a critical role in the
      etiology of inflammatory lung diseases. Nitric oxide (NO) has been suggested to
      play an antiinflammatory role through S-nitrosation of components of NF-kappaB
      pathway. NO production can be modulated by changing the availability of its
      substrate, L-arginine. Arginases compete with NO synthases (NOSs) for their
      common substrate, L-arginine, and thereby have the potential to alter the
      signaling function of NO. The goal of the present study was to determine the
      impact of arginase manipulation on NO, and subsequent effects on NF-kappaB
      activation, in lung epithelial cells. Our results demonstrate that reduction of
      arginase activity enhanced cellular content of NO and S-nitrosated proteins, and
      resulted in decreases in TNF-alpha- or LPS-stimulated NF-kappaB DNA binding and
      transcriptional activity, in association with enhanced S-nitrosation of p50. The
      effects of arginase inhibition on NF-kappaB were reversed by the generic NOS
      inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME), suggesting a causal
      role for NO in the attenuation of NF-kappaB induced by arginase suppression.
      Conversely, overexpression of arginase I decreased cellular S-nitrosothiol
      content and enhanced IkappaB kinase activity and NF-kappaB DNA binding, and
      decreased S-nitrosation of p50. Collectively, our data point to a regulatory
      mechanism wherein NF-kappaB is controlled through arginase-dependent regulation
      of NO levels, which may impact on chronic inflammatory diseases that are
      accompanied by NF-kappaB activation and upregulation of arginases.

PMID- 17218618
TI  - Effects of continuous positive airway pressure on cerebral vascular response to
      hypoxia in patients with obstructive sleep apnea.
AB  - RATIONALE: The mechanism leading to increased risk of stroke in patients with
      obstructive sleep apnea (OSA) is unknown. It may occur through alteration in the
      regulation of cerebral blood flow, reflected in part by the response of the
      cerebral vasculature to hypoxia. We hypothesized that the cerebrovascular
      response to hypoxia is reduced in patients with OSA. OBJECTIVE: To determine the
      cerebral blood flow response to hypoxia in patients with OSA. METHODS: The
      cerebral blood flow response to 20 minutes of isocapnic hypoxia was measured in
      eight male patients with OSA before and after 4 to 6 weeks of continuous positive
      airway pressure (CPAP) therapy and in 10 matched healthy control subjects.
      MEASUREMENTS AND MAIN RESULTS: The cerebral blood flow response to hypoxia was
      significantly lower in patients with OSA compared with control subjects (0.56 +/-
      0.10 vs. 0.97 +/- 0.09% [mean +/- SE] change in blood flow velocity per %
      desaturation; p=0.007). After CPAP therapy, the cerebral blood flow response to
      hypoxia was similar between patients with OSA and control subjects (1.08 +/- 0.15
      vs. 0.92 +/- 0.13% change in blood flow velocity per % desaturation; p=0.4).
      Moderately strong correlations were found between the cerebral blood flow
      response to hypoxia and the apnea-hypopnea index (r=-0.57; p=0.04) and nocturnal
      oxyhemoglobin saturation (r=0.48; p=0.01). CONCLUSIONS: The cerebral blood flow
      response to hypoxia is significantly reduced in patients with OSA. Treatment of
      OSA with CPAP increases the cerebral blood flow response to hypoxia to normal
      levels. An attenuated cerebrovascular response to hypoxia in patients with OSA
      may contribute to their elevated risk of stroke.

PMID- 17218619
TI  - Use of flow-volume curves to predict oral appliance treatment outcome in
      obstructive sleep apnea.
AB  - BACKGROUND: It has been recognized that mandibular advancement splint (MAS)
      treatment is effective in some, but not all, patients with obstructive sleep
      apnea (OSA). Hence there is a need for a simple and reliable clinical tool to
      assist in the differentiation of treatment responses. We hypothesized that
      abnormalities of flow-volume curves, together with other clinical variables, may
      have clinical utility in the prediction of MAS treatment outcome. METHODS: Fifty
      four patients with known OSA underwent MAS treatment. Expiratory and inspiratory
      flow-volume curves were measured in the erect and supine positions to derive
      midinspiratory flow (MIF(50)) and the ratio of expiratory to inspiratory flow at
      50% of vital capacity (MEF(50):MIF(50)). Multivariable logistic regression was
      performed to identify additional significant clinical variables in the prediction
      of treatment outcome. RESULTS: The mean (+/- SD) apnea-hypopnea index (AHI) in 35
      responders was significantly reduced from 28.9 +/- 13.7 to 6.7 +/- 5.8/hour
      (p<0.001). In 19 nonresponders there was no significant change in AHI. MIF(50)
      was lower (6.04 +/- 1.80 vs. 6.88 +/- 1.08 L/second; p=0.035) and the
      MEF(50):MIF(50) ratio was higher (0.82 +/- 0.23 vs. 0.61 +/- 0.15; p=0.001) in
      responders than nonresponders. Logistic regression analysis revealed that the
      MEF(50):MIF(50) ratio was the most important predictive factor for MAS treatment
      outcome, but that body mass index, age, and baseline AHI were also contributory.
      CONCLUSIONS: These data suggest that flow-volume curves, in combination with
      other factors such as body mass index, age, and baseline AHI, may have a useful
      clinical role in the prediction of treatment outcome with MAS.

PMID- 17218621
TI  - Prognosis of fibrotic interstitial pneumonia: idiopathic versus collagen vascular
      disease-related subtypes.
AB  - BACKGROUND: To investigate whether the better prognosis of interstitial
      pneumonias associated with collagen vascular disease (CVD) compared with
      idiopathic interstitial pneumonia (IIP) is due to higher frequency of the
      nonspecific interstitial pneumonia (NSIP) pattern in CVD, we compared the
      outcomes of patients from these two groups with the same histopathologic pattern.
      SUBJECTS: The clinical features and survival of 362 patients (269 with IIP and 93
      with CVD) diagnosed using surgical lung biopsy were analyzed. RESULTS: The mean
      survival of the CVD group (131.0 mo) was longer than that of the IIP group (80.5
      mo) (p<0.0001). The patients with usual interstitial pneumonia pattern among the
      CVD group (n=36) was younger, female, and predominantly nonsmoking compared with
      the IIP group (n=203). Although baseline lung functions were not significantly
      different, the CVD group survived longer (mean, 177.0 mo) than the IIP group
      (mean, 66.9 +/- 6.5 mo; p=0.001). By multivariate analysis, younger age, better
      pulmonary function, and the presence of a CVD were independent prognostic
      factors. In NSIP pattern, no significant differences in survival, clinical
      features, or lung function were found between the two groups. CONCLUSION: Our
      data suggest that the better prognosis of patients in the CVD group is not solely
      due to the predominance of the NSIP pattern. The prognosis of patients with the
      usual interstitial pneumonia pattern in CVD is better than in those with
      idiopathic pulmonary fibrosis, despite the same pathologic pattern. In contrast,
      in those with an NSIP pattern, the prognosis is similar in both groups.

PMID- 17218622
TI  - Effects of foot orthoses on patients with chronic ankle instability.
AB  - Chronic instability of the ankle can be the result of mechanical and functional
      deficits. An acute ankle sprain can cause mechanical and functional instability,
      which may or may not respond to standard rehabilitation programs. Chronic
      instability results when there is persistent joint laxity of the ankle or when
      one or more components of neuromuscular control of the ankle are compromised. A
      loss of balance or postural control seems to be the most consistent finding among
      athletes with chronic instability of the ankle. Recent research in patients with
      acute and chronic ankle instability has revealed positive effects of foot
      orthoses on postural control. This article reviews the current research relevant
      to the use of foot orthoses in patients with chronic ankle instability and
      clarifies the suggested benefits and the shortcomings of these investigations.

PMID- 17218620
TI  - Comparison of an interferon-gamma release assay with tuberculin skin testing in
      HIV-infected individuals.
AB  - RATIONALE: Although interferon (IFN)-gamma release assays are approved for the
      diagnosis of latent tuberculosis infection (LTBI), limited data exist regarding
      their performance in HIV infection. OBJECTIVES: To compare tuberculin skin test
      (TST) results to the commercial IFN-gamma release assay QuantiFERON-TB Gold In
      Tube (QFT) for the diagnosis of LTBI in HIV-infected adults. METHODS: A total of
      294 HIV-infected subjects sampled from two San Francisco cohorts underwent TST,
      using 5 TU of purified protein derivative, and QFT, measuring IFN-gamma response
      to Mycobacterium tuberculosis-specific RD-1 antigens. MAIN RESULTS: Of 294
      participants, 205 (70%) returned for an evaluable TST. Concordance between QFT
      and TST was 89.3% (kappa=0.37, p=0.007). However, in subjects with positive test
      results by either TST or QFT, only 28% (8/29) had positive test results by both
      modalities. TST-positive/QFT-negative discordant results were found in 5.1% of
      subjects and TST-negative/QFT-positive discordance in 5.6%. Indeterminate QFT
      results occurred in 5.1%, all due to a failure to respond to the
      phytohemagglutinin-positive control. Subjects with a CD4(+) count of less than
      100 cells/mm(3) had a relative risk of an indeterminate result of 4.24 (95%
      confidence interval, 1.55-11.61; p=0.003) compared with those with a CD4(+) count
      of 100 or more. CONCLUSIONS: Overall concordance between QFT and TST in HIV
      infection was high, but agreement among subjects with positive tests by either
      modality was low.

PMID- 17218623
TI  - Medial tibial stress syndrome (tibial fasciitis): a proposed pathomechanical
      model involving fascial traction.
AB  - Although medial tibial stress syndrome is one of the most common lower-extremity
      overuse injuries, its pathomechanics remain controversial. Two popular theories
      have been proposed to account for this condition: tibial bending and fascial
      traction. This article evaluates the role of fascial traction in medial tibial
      stress pathomechanics. We hypothesized that with contraction of the deep leg
      flexors tension would be imparted to the tibial fascial attachment at the medial
      tibial crest. We also speculated that circumferential straps would dampen tension
      directed to the medial tibial crest. The amount of strain present in the tibial
      fascia adjacent to its distal medial tibial crest insertion during loading of the
      leg was investigated as a descriptive laboratory pilot study using three fresh
      cadaver specimens. Strain in the distal tibial fascia was measured using strain
      gauges placed in the fascia at its medial tibial crest insertion. As tension on
      the posterior tibial, flexor digitorum longus, and soleus tendons increased,
      strain in the tibial fascia increased in a consistent linear manner (P < .0001).
      We conclude that fascial tension may play a role in the pathomechanics of medial
      tibial stress syndrome. The tenting effect of the posterior tibial, flexor
      digitorum longus, and soleus tendons caused by muscle contraction exerts a force
      on the distal tibial fascia that is directed to its tibial crest insertion.
      Circumferential straps provided no dampening effect on tension directed to the
      medial tibial crest.

PMID- 17218624
TI  - Achilles tendon sports injuries: a review of classification and treatment.
AB  - Achilles tendon injuries are among the three most frequent sports-related
      injuries of the foot and ankle. Proper function of the Achilles tendon is
      critical to performance in sports. A thorough knowledge of the anatomy and
      biomechanical function of this tendon is essential to the effective treatment of
      these injuries. Distinguishing among the various pathologies of the Achilles
      tendon is an important first step toward successful treatment and return of the
      athlete to sports activity. The term Achilles tendinitis is a nonspecific
      diagnosis that does not accurately describe an actual injury. This review is
      intended to provide the sports medicine physician with a means of classifying
      Achilles tendon injuries and, thus, arriving at an accurate diagnosis and
      treatment plan.

PMID- 17218626
TI  - Magnetic resonance imaging in the evaluation of sports injuries of the foot and
      ankle: a pictorial essay.
AB  - Magnetic resonance imaging is playing an increasingly important role in
      evaluation of the injured athlete's foot and ankle. Magnetic resonance imaging
      allows accurate detection of bony abnormalities, such as stress fractures, and
      soft-tissue abnormalities, including ligament tears, tendon tears, and
      tendinopathy. The interpreter of magnetic resonance images should systematically
      review the images, noting normal structures and accounting for changes in soft
      tissue and bony signal.

PMID- 17218625
TI  - Clinical uses of in-shoe pressure analysis in podiatric sports medicine.
AB  - Athletic injuries of the foot and lower extremity are commonly treated with
      custom foot orthoses. These devices usually provide immediate relief of the
      athlete's pain and dysfunction. Occasionally, however, they do not help, or even
      increase the patient's discomfort. We discuss a method of using in-shoe pressure
      measurement systems to analyze the athletic patient's foot and lower-extremity
      function before and after treatment with custom foot orthoses, with a focus on
      sagittal plane biomechanics. Case histories are presented of athletes whose gait
      pathologies were identified and treated successfully using an in-shoe pressure
      measurement system.

PMID- 17218627
TI  - Current approaches to the management of plantar heel pain syndrome, including the
      role of injectable corticosteroids.
AB  - Plantar heel pain syndrome, which has a multifactorial and widely disputed
      etiology, affects more than 2 million people annually. A survey was conducted of
      members of the American Academy of Podiatric Sports Medicine about their
      strategies for managing plantar heel pain syndrome, especially the role of
      injectable corticosteroids. The respondents tended to be experienced (10-24 years
      in practice) podiatric physicians with a concentration in sports medicine. They
      reported that for early-stage plantar heel pain syndrome they generally recommend
      avoidance of wearing flat shoes and walking barefoot (92%), use of over-the
      counter arch supports and heel cushions (90%), regular stretching of the calf
      muscles (88%), strapping of the foot (75%), cryotherapy applied directly to the
      affected part of the foot (67%), and nonsteroidal anti-inflammatory drug therapy
      (60%). When these measures fail to relieve heel pain, most of the responding
      podiatric physicians recommend using custom orthotic devices (60%) and
      corticosteroid injections (60%) as intermediate therapy. Surgical plantar
      fasciotomy (88%), cast immobilization (77%), and extracorporeal shockwave therapy
      (69%) are generally recommended as late-stage therapy for resistant cases. A
      staged approach seems to yield the best results in treatment of this common
      condition.

PMID- 17218628
TI  - Biomechanical evaluation of dancers and assessment of their risk of injury.
AB  - Professional dancers have a 90% risk of injury during their career. The lower
      extremity is involved in approximately 75% of the injuries sustained by dancers.
      Proper biomechanical evaluation, risk assessment, and prevention-oriented
      treatment are necessary to minimize future problems and promote a full and
      lasting recovery when an injury is sustained. This article outlines the in-office
      evaluation process and discusses backstage care.

PMID- 17218629
TI  - Return-to-activity levels in 96 athletes with stress fractures of the foot,
      ankle, and leg: a retrospective analysis.
AB  - Stress fractures of the foot and ankle are common in the athletic population.
      Because this population is especially eager to return to activity, such fractures
      can be challenging to treat. If the biomechanical faults are not addressed or
      gradual return to activity is not monitored appropriately, fractures occasionally
      recur. A retrospective analysis was conducted of 96 athletes who presented to a
      podiatric sports medicine practice over the course of 10 years with stress
      fractures confirmed by radiograph or bone scan. The most common type of fracture
      sustained by this population was tibial stress fracture, followed by second
      metatarsal fracture. Marathon training was the most common pre-injury activity
      overall, although fitness walking was the most common activity among those with
      metatarsal fractures. This study relates the most common types of stress
      fractures of the foot, ankle, and leg to certain athletic activities and
      correlates duration of symptoms before presentation with return-to-activity time.

PMID- 17218630
TI  - Tibial sesamoid fracture in a softball player.
AB  - A single case of a tibial sesamoid fracture in a softball player is reported
      here. A review of the literature confirms that this is an unusual and difficult
      problem to treat in the athletic population given the significant loads placed on
      the sesamoids during athletic activity. In the case presented, conservative care
      was not effective, and the athlete underwent surgical excision of the fractured
      sesamoid. With use of a postoperative orthosis and cleat modification, surgical
      management was successful and allowed the athlete to return to her athletic
      endeavors without restrictions in 8 weeks.

PMID- 17218634
TI  - XR5944: A potent inhibitor of estrogen receptors.
AB  - The anticancer drug XR5944 was originally developed as a topoisomerase inhibitor
      and was subsequently shown to be a transcription inhibitor. It has shown
      exceptional anticancer activity both in vitro and in vivo and was significantly
      more potent than traditional topoisomerase inhibitors. The solution structure of
      the XR5944/DNA complex recently obtained in our laboratory indicates that XR5944
      bis-intercalates at the 5'-(TpG):(CpA) site of duplex DNA, which is found in the
      consensus DNA-binding site of estrogen receptor (ER). Thus, we tested the ability
      of XR5944 to inhibit ER activity both in vitro and in cultured cells. In
      electrophoretic mobility shift assays, it is seen that the DNA binding of
      recombinant ERalpha protein, as well as ER from nuclear extracts, is inhibited by
      XR5944 in a dose-dependent manner. In luciferase reporter assays, XR5944
      inhibited the reporter gene expression from an estrogen response element
      containing promoter but not from a basal promoter sequence that lacks any cis
      acting elements. In contrast, the RNA polymerase inhibitor actinomycin D inhibits
      the transcription from both the above-mentioned promoters. The specificity of
      XR5944 activity is displayed by a separate reporter assay in which the
      transactivation of reporter gene expression by Sp1 proteins was not inhibited by
      XR5944. Collectively, these data suggest that XR5944 is capable of specifically
      inhibiting the binding of ER to its consensus DNA sequence and its subsequent
      activity. This represents a novel mechanism of ER inhibition, which may allow the
      development of agents capable of overcoming resistance to current antiestrogens.

PMID- 17218635
TI  - Suberoylanilide hydroxamic acid (vorinostat) represses androgen receptor
      expression and acts synergistically with an androgen receptor antagonist to
      inhibit prostate cancer cell proliferation.
AB  - Growth of prostate cancer cells is initially dependent on androgens, and androgen
      ablation therapy is used to control tumor growth. Unfortunately, resistance to
      androgen ablation therapy inevitably occurs, and there is an urgent need for
      better treatments for advanced prostate cancer. Histone deacetylase inhibitors,
      such as suberoylanilide hydroxamic acid (SAHA; vorinostat), are promising agents
      for the treatment of a range of malignancies, including prostate cancer. SAHA
      inhibited growth of the androgen-responsive LNCaP prostate cancer cell line at
      low micromolar concentrations and induced caspase-dependent apoptosis associated
      with chromatin condensation, DNA fragmentation, and mitochondrial membrane
      depolarization at higher concentrations (>/=5 mumol/L). Gene profiling and
      immunoblot analyses showed a decrease in androgen receptor (AR) mRNA and protein
      in LNCaP cells cultured with SAHA compared with control cells, with a
      corresponding decrease in levels of the AR-regulated gene, prostate-specific
      antigen. Culture of LNCaP cells in steroid-free medium markedly sensitized the
      cells to SAHA. Moreover, a combination of low, subeffective doses of SAHA and the
      AR antagonist bicalutamide resulted in a synergistic reduction in cell
      proliferation and increase in caspase-dependent cell death. Addition of exogenous
      androgen prevented the induction of cell death, indicating that suppression of
      androgen signaling was required for synergy. At the subeffective concentrations,
      these agents had no effect, alone or in combination, on proliferation or death of
      AR-negative PC-3 prostate cancer cells. Our findings indicate that SAHA is
      effective in targeting the AR signaling axis and that androgen deprivation
      sensitizes prostate cancer cells to SAHA. Consequently, combinatorial treatments
      that target different components of the AR pathway may afford a more effective
      strategy to control the growth of prostate cancer cells.

PMID- 17218637
TI  - Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance
      chemotherapy in human bladder cancer cells.
AB  - Heat shock protein 27 (Hsp27) is a cytoprotective chaperone that is
      phosphoactivated during cell stress that prevents aggregation and/or regulate
      activity and degradation of certain client proteins. Recent evidence suggests
      that Hsp27 may be involved in tumor progression and the development of treatment
      resistance in various tumors, including bladder cancer. The purpose of this study
      was to examine, both in vitro and in vivo, the effects of overexpression of Hsp27
      and, correspondingly, the down-regulation of Hsp27 using small interfering (si)
      RNA and OGX-427, a second-generation antisense oligonucleotide targeting Hsp27.
      Hsp27 overexpression increased UMUC-3 cell growth and resistance to paclitaxel.
      Both OGX-427 and Hsp27 siRNA decreased Hsp27 protein and mRNA levels by >90% in a
      dose- and sequence-specific manner in human bladder cancer UMUC-3 cells. OGX-427
      or Hsp27 siRNA treatment induced apoptosis and enhanced sensitivity to paclitaxel
      in UMUC-3 cells. In vivo, OGX-427 significantly inhibited tumor growth in mice,
      enhanced sensitivity to paclitaxel, and induced significantly higher levels of
      apoptosis compared with xenografts treated with control oligonucleotides.
      Collectively, these findings suggest that Hsp27 knockdown with OGX-427 and
      combined therapy with paclitaxel could be a novel strategy to inhibit the
      progression of bladder cancer.

PMID- 17218636
TI  - Adenovirus type 5 E1A gene therapy for ovarian clear cell carcinoma: a potential
      treatment strategy.
AB  - Resistance of ovarian clear cell carcinoma (CCC) to platinum-based chemotherapy
      is associated with poor prognosis, and an effective treatment for advanced
      disease is urgently needed. HER2/neu is up-regulated more often in CCC than in
      other histologic types of epithelial ovarian cancer. The purpose of this study
      was to assess possible treatment for ovarian CCC with the anti-HER2 antibody
      trastuzumab or human adenovirus type 5 E1A. We treated 10 CCC cell lines with
      trastuzumab or E1A and assessed cell viability, proliferation, and colony
      formation and the expression of HER2 and wild-type p53 proteins and molecules
      downstream of those signaling pathways. HER2 protein was detected at various
      levels in all 10 cell lines by Western blotting and in 5 CCC cell lines by
      immunohistochemical staining; HER2 gene amplification was detected (by
      fluorescence in situ hybridization) in only one cell line (RMG-I). Trastuzumab
      did not inhibit proliferation in any of the four CCC cell lines tested (RMG-I,
      SKOV-2, OVTOKO, and OVSAYO). However, transfection with E1A (as compared with
      control vectors) reduced colony formation in all 10 CCC cell lines regardless of
      HER2 expression level. Infection of RMG-I and SMOV-2 cells with an adenoviral
      vector encoding E1A led to significant (P < 0.05) suppression of proliferation
      and enhancement of cell death; this effect required stabilization of p53 (but not
      p73) protein and was associated with the up-regulation of Bax and the cleavage of
      caspase-9. Other mechanisms, such as p53-independent apoptosis, may also be
      involved in E1A-mediated cell death in CCC. Finally, treatment with E1A prolonged
      survival in a CCC xenograft model (P < 0.001). E1A gene therapy, because of its
      ability to stabilize wild-type p53, is worth exploring as a treatment modality
      for women with ovarian CCC, which typically expresses wild-type p53.

PMID- 17218638
TI  - Characterization of a potent and selective small-molecule inhibitor of the PIM1
      kinase.
AB  - The pim-1 kinase is a true oncogene that has been implicated in the development
      of leukemias, lymphomas, and prostate cancer, and is the target of drug
      development programs. We have used experimental approaches to identify a
      selective, cell-permeable, small-molecule inhibitor of the pim-1 kinase to foster
      basic and translational studies of the enzyme. We used an ELISA-based kinase
      assay to screen a diversity library of potential kinase inhibitors. The flavonol
      quercetagetin (3,3',4',5,6,7-hydroxyflavone) was identified as a moderately
      potent, ATP-competitive inhibitor (IC(50), 0.34 micromol/L). Resolution of the
      crystal structure of PIM1 in complex with quercetagetin or two other flavonoids
      revealed a spectrum of binding poses and hydrogen-bonding patterns in spite of
      strong similarity of the ligands. Quercetagetin was a highly selective inhibitor
      of PIM1 compared with PIM2 and seven other serine-threonine kinases.
      Quercetagetin was able to inhibit PIM1 activity in intact RWPE2 prostate cancer
      cells in a dose-dependent manner (ED(50), 5.5 micromol/L). RWPE2 cells treated
      with quercetagetin showed pronounced growth inhibition at inhibitor
      concentrations that blocked PIM1 kinase activity. Furthermore, the ability of
      quercetagetin to inhibit the growth of other prostate epithelial cell lines
      varied in proportion to their levels of PIM1 protein. Quercetagetin can function
      as a moderately potent and selective, cell-permeable inhibitor of the pim-1
      kinase, and may be useful for proof-of-concept studies to support the development
      of clinically useful PIM1 inhibitors.

PMID- 17218639
TI  - Phylogenetic evidence for deleterious mutation load in RNA viruses and its
      contribution to viral evolution.
AB  - Populations of RNA viruses are often characterized by abundant genetic variation.
      However, the relative fitness of these mutations is largely unknown, although
      this information is central to our understanding of viral emergence, immune
      evasion, and drug resistance. Here we develop a phylogenetic method, based on the
      distribution of nonsynonymous and synonymous changes, to assess the relative
      fitness of polymorphisms in the structural genes of 143 RNA viruses. This reveals
      that a substantial proportion of the amino acid variation observed in natural
      populations of RNA viruses comprises transient deleterious mutations that are
      later purged by purifying selection, potentially limiting virus adaptability. We
      also demonstrate, for the first time, the existence of a relationship between
      amino acid variability and the phylogenetic distribution of polymorphisms. From
      this relationship, we propose an empirical threshold for the maximum viable
      deleterious mutation load in RNA viruses.

PMID- 17218640
TI  - Multilocus analysis of nucleotide variation of Oryza sativa and its wild
      relatives: severe bottleneck during domestication of rice.
AB  - Varying degrees of reduction of genetic diversity in crops relative to their wild
      progenitors occurred during the process of domestication. Such information,
      however, has not been available for the Asian cultivated rice (Oryza sativa)
      despite its importance as a staple food and a model organism. To reveal levels
      and patterns of nucleotide diversity and to elucidate the genetic relationship
      and demographic history of O. sativa and its close relatives (Oryza rufipogon and
      Oryza nivara), we investigated nucleotide diversity data from 10 unlinked nuclear
      loci in species-wide samples of these species. The results indicated that O.
      rufipogon and O. nivara possessed comparable levels of nucleotide variation
      ((sil) = 0.0077 approximately 0.0095) compared with the relatives of other crops.
      In contrast, nucleotide diversity of O. sativa was as low as (sil) = 0.0024 and
      even lower ((sil) = 0.0021 for indica and 0.0011 for japonica), if we consider
      the 2 subspecies separately. Overall, only 20-10% of the diversity in the wild
      species was retained in 2 subspecies of the cultivated rice (indica and
      japonica), respectively. Because statistic tests did not reject the assumption of
      neutrality for all 10 loci, we further used coalescent to simulate bottlenecks
      under various lengths and population sizes to better understand the domestication
      process. Consistent with the dramatic reduction in nucleotide diversity, we
      detected a severe domestication bottleneck and demonstrated that the sequence
      diversity currently found in the rice genome could be explained by a founding
      population of 1,500 individuals if the initial domestication event occurred over
      a 3,000-year period. Phylogenetic analyses revealed close genetic relationships
      and ambiguous species boundary of O. rufipogon and O. nivara, providing
      additional evidence to treat them as 2 ecotypes of a single species. Lowest
      linkage disequilibrium (LD) was found in the perennial O. rufipogon where the
      r(2) value dropped to a negligible level within 400 bp, and the highest in the
      japonica rice where LD extended to the entirely sequenced region ( approximately
      900 bp), implying that LD mapping by genome scans may not be feasible in wild
      rice due to the high density of markers needed.

PMID- 17218641
TI  - No evidence for an mtDNA role in sperm motility: data from complete sequencing of
      asthenozoospermic males.
AB  - The first complete mitochondrial DNA (mtDNA) sequences (approximately 16,569 bp)
      in 20 patients with asthenozoospermia and a comparison with 23 new complete mtDNA
      sequences in teratoasthenozoospermic individuals, confirmed no sharing of
      specific polymorphisms or specific mitochondrial lineages between these
      individuals. This is strong evidence against the accepted claim of a major role
      played by mtDNA in male fertility, once supported by haplogroup association
      studies based on the screening of hypervariable region I. The hypothesis of
      maternally driven selection acting in male reproductive success must thus be
      treated with caution.

PMID- 17218642
TI  - Rearrangement rate following the whole-genome duplication in teleosts.
AB  - It is now clear that a whole-genome duplication (WGD) occurred at the base of the
      teleost fish lineage. Like the other anciently polyploid genomes investigated so
      far, teleost genomes now behave like diploids with chromosomes forming pairs at
      meiosis. The diploidization process is currently poorly understood. It is
      associated with many gene deletions, such that one of the duplicates is lost at
      most loci and has also been proposed to coincide with an increase in genomic
      instability. Here we ask whether WGD is a determinant of the genomic
      rearrangement rate in teleosts. We study variability of the rates of
      rearrangement along a vertebrate phylogenetic tree, composed of 3 tetrapods
      (human, chicken, and mouse) and 3 teleost fishes (zebrafish, Tetraodon, and
      Takifugu), whose complete genome sequences are available. We devise a simple
      parsimony method for counting rearrangements, which takes into account various
      methodological complications caused by the WGD and the subsequent gene losses. We
      show that there does appear to be an increase in rearrangement rate after WGD,
      but that there is also a great deal of additional variability in rearrangement
      rates across species.

PMID- 17218644
TI  - Is the adoption and safe families act influencing child welfare outcomes for
      families with substance abuse issues?
AB  - The Adoption and Safe Families Act (ASFA) was designed to promote more timely
      permanent placements for children in the child welfare system. To date, however,
      available data have said little about whether ASFA is meeting its intended goals.
      This study looks at the impact of ASFA on parents struggling with substance abuse
      issues. The authors compared child welfare outcomes, pre- and post-ASFA, for
      children of more than 1,900 substance-abusing women with some treatment
      involvement. After the implementation of ASFA, children in this study spent less
      time in foster care, were placed in permanent settings more quickly, and were
      more likely to be adopted than remain in long-term foster care. The proportion of
      children who were reunified with their parent or parents stayed the same. These
      outcomes were apparent even controlling for case and family characteristics.
      Results are discussed in terms of the influence of ASFA on service delivery
      systems.

PMID- 17218643
TI  - The evolutionary history of human and chimpanzee Y-chromosome gene loss.
AB  - Recent studies have suggested that gene gain and loss may contribute
      significantly to the divergence between humans and chimpanzees. Initial
      comparisons of the human and chimpanzee Y-chromosomes indicate that chimpanzees
      have a disproportionate loss of Y-chromosome genes, which may have implications
      for the adaptive evolution of sex-specific as well as reproductive traits,
      especially because one of the genes lost in chimpanzees is critically involved in
      spermatogenesis in humans. Here we have characterized Y-chromosome sequences in
      gorilla, bonobo, and several chimpanzee subspecies for 7 chimpanzee gene
      disruptive mutations. Our analyses show that 6 of these gene-disruptive mutations
      predate chimpanzee-bonobo divergence at approximately 1.8 MYA, which indicates
      significant Y-chromosome change in the chimpanzee lineage relatively early in the
      evolutionary divergence of humans and chimpanzees.

PMID- 17218645
TI  - Substance use in maltreated youth: findings from the national survey of child and
      adolescent well-being.
AB  - The purpose of this study was to describe the characteristics associated with
      different levels of substance use in a national probability sample of maltreated
      11- to 15-year-olds (n = 1,179). Bivariate (chi-square tests) and multivariate
      (logistic regression) analyses were used to examine the association of adolescent
      substance use with demographics, placement type, and youth and family
      characteristics. Seventy-one percent of youth reported no use, 20% reported low
      levels of substance use, and approximately 9% reported moderate to high levels of
      use. Youth substance use was similar across placement types. Conduct problems and
      low caregiver relatedness were more prevalent for youth reporting higher levels
      of substance use. High levels of conduct problems increased the odds of substance
      use, whereas high caregiver monitoring decreased the odds of substance use.
      Caregiver monitoring may be a key tactic in attempts to reduce the likelihood of
      substance use in maltreated youth, regardless of placement type.

PMID- 17218646
TI  - Pathways to collaboration: exploring values and collaborative practice between
      child welfare and substance abuse treatment fields.
AB  - Although recent research has highlighted the importance of "bridging the gap"
      between child welfare and substance abuse treatment delivery systems, few studies
      examine specific factors that may facilitate such collaboration. This study
      examined similarities and differences in values and perceived capacity for
      collaboration between substance abuse and child welfare fields based on survey
      data from more than 350 respondents in 12 California counties. Although
      respondents across disciplines held similar values in some areas, such as
      priorities for services, significant differences between respondents from child
      welfare and substance abuse fields were found in other areas, including values
      and beliefs about drug use and drug-using parents, funding, and planning and
      measurement of outcomes. Respondents from counties with a strong history of
      collaboration were more likely to report institutionalized collaborative
      practices in several areas, from use of multidisciplinary teams for case planning
      to use of multiyear budgeting to plan for integrated services.

PMID- 17218647
TI  - How effective are family treatment drug courts? Outcomes from a four-site
      national study.
AB  - Family treatment drug courts (FTDCs) are a rapidly expanding program model
      designed to improve treatment and child welfare outcomes for families involved in
      child welfare who have substance abuse problems. The present study compares
      outcomes for 250 FTDC participants to those of similar parents who did not
      receive FTDC services in four sites. Results show that FTDC parents, compared to
      comparison parents, entered substance abuse treatment more quickly, stayed in
      treatment longer, and completed more treatment episodes. Furthermore, children of
      FTDC parents entered permanent placements more quickly and were more likely to be
      reunified with their parents, compared to children of non-FTDC participants.
      Finally, the FTDC program appears to have a "value added" in facilitating
      positive child welfare outcomes above and beyond the influence of positive
      treatment experiences.

PMID- 17218648
TI  - Repeated questions, deception, and children's true and false reports of body
      touch.
AB  - Four- to 7-year-olds' ability to answer repeated questions about body touch
      either honestly or dishonestly was examined. Children experienced a play event,
      during which one third of the children were touched innocuously. Two weeks later,
      they returned for a memory interview. Some children who had not been touched were
      instructed to lie during the interview and say that they had been touched.
      Children so instructed were consistent in maintaining the lie but performed
      poorly when answering repeated questions unrelated to the lie. Children who were
      not touched and told the truth were accurate when answering repeated questions.
      Of note, children who had been touched and told the truth were the most
      inconsistent. Results call into question the common assumption that consistency
      is a useful indicator of veracity in children's eyewitness accounts.

PMID- 17218649
TI  - Development and confirmatory factor analysis of the community norms of child
      neglect scale.
AB  - This article describes the development of the Community Norms of Child Neglect
      Scale (CNCNS), a new measure of perceptions of child neglect, for use in
      community samples. The CNCNS differentiates among four subtypes of neglect
      (failure to provide for basic needs, lack of supervision, emotional neglect, and
      educational neglect). Scenarios ranging in seriousness for each subtype were
      presented to a large community sample (N = 3,809). Confirmatory factor analyses
      indicated that a four-factor model provided a better fit to the data than did a
      model specifying only one overall neglect factor, suggesting this sample
      distinguished among the four subtypes of neglect. The authors tested measurement
      equivalence across individuals who work with children and lay community
      respondents and across rural and urban respondents, with results indicating a
      very similar structure across these groups. These initial reliability and
      validity data suggest that the CNCNS may be of use in comparing perceptions of
      child neglect among individuals and across communities.

PMID- 17218650
TI  - Risk of death among children reported for nonfatal maltreatment.
AB  - This article presents analyses of longitudinal data to explore whether low-income
      children who survived a first incident of reported maltreatment were at higher
      risk of later childhood death compared to a matched comparison group of low
      income children without reports of maltreatment (n = 7,433). Compared to the
      comparison group, children in the maltreatment group had about twice the risk of
      death before age 18 (0.51% vs. 0.27%). Among children with mal-treatment reports,
      median time from the first report to subsequent death was 9 months. The majority
      of deaths among children who were reported for maltreatment could be categorized
      as preventable (accidents or recurrent maltreatment) as compared to resulting
      from severe health conditions.

PMID- 17218651
TI  - Measuring the risk of physical neglect in a population-based sample.
AB  - Child neglect accounts for the majority of officially substantiated cases of
      child maltreatment in this country, although population-based data are lacking.
      This study estimates the number of children at risk for specific subtypes of
      physical neglect, using results of an anonymous telephone survey administered to
      1,435 mothers of children ages 0 to 17 years in North and South Carolina.
      Children were considered "at risk for neglect" from lack of enough food, lack of
      access to medical care when needed, and inadequate supervision. Demographic
      factors were significantly related to the outcomes of interest, including lower
      family income with lack of enough food and access to medical care. There was
      little overlap in children at risk for the different subtypes of neglect.
      Maternal self-report data can be used to improve researchers' understanding of
      children at risk for neglect and to explore gaps in knowledge that might be
      amenable to intervention and prevention efforts.

PMID- 17218652
TI  - Sports after hip resurfacing arthroplasty.
AB  - BACKGROUND: No information is available concerning patients' sports activity
      after hip resurfacing arthroplasty. HYPOTHESIS: Patients treated by hip
      resurfacing arthroplasty will be able to achieve a high level of sports activity.
      STUDY DESIGN: Case series; Level of evidence, 4. METHODS: We surveyed 112
      patients by postal questionnaire to determine their sporting activities at a mean
      of 23.5 (range, 9-40) months after hip resurfacing surgery. Data were also
      analyzed separately for older and younger patients and women and men,
      respectively. RESULTS: Of 112 patients, 110 participated in an average of 4.6
      sport disciplines after surgery, compared with 105 patients pre-operatively
      engaged in an average of 4.8 disciplines. About 26% performed sports 4 times per
      week or more--almost 60% for longer than 60 min at each session. A high
      proportion of our patients were still engaged in downhill skiing (51%) and in
      high-impact disciplines such as tennis (12%) or contact sports (22%). More than
      50% of the patients commenced sports within the first 3 months after surgery.
      During activities, 70% were completely pain-free. The group of older patients
      (mean age, 60.2 years) participated in more different disciplines with a higher
      weekly frequency and longer session length than younger patients (mean age, 46.4
      years). CONCLUSION: The present study reports for the first time on the detailed
      sports activity and activity extent after hip resurfacing arthroplasty. Our
      patients could return to a high level of sports participation after surgery. Age
      related differences were found that have not yet been published. Nevertheless,
      further follow-up is necessary to assess the influence of high-level activity on
      loosening and revision rates after hip resurfacing arthroplasty.

PMID- 17218653
TI  - Forefoot loading during 3 athletic tasks.
AB  - BACKGROUND: Due to the popularity of soccer and the high incidence of injury
      among soccer players, it is valuable to know the effects of tasks like side cuts,
      crossover cuts, and forward acceleration on the foot. PURPOSE: To determine the
      differences in forefoot loading during three different athletic tasks. STUDY
      DESIGN: Descriptive laboratory study. METHODS: Thirty-six subjects (17 women and
      19 men) were tested. Subjects ran a slalom-style agility course 5 times while
      plantar pressure data was collected at 100 Hz. Plantar pressure was recorded
      under both feet; however, a right-foot contact was used in the analysis of the
      side-cut task, a left-foot plant was used in the analysis of the crossover cut,
      and an average of the 3 steps of acceleration were used in the analysis. The peak
      pressure, contact area, and contact time for the entire foot were compared
      between the 3 tasks. The force and the force-time integral were obtained during 5
      trials for each of the 3 tasks. The foot was divided into 8 masked regions, which
      were used to determine the loading patterns specifically in the forefoot. Each
      variable was analyzed using a 1 x 3 analysis of variance to determine differences
      between the three movement tasks in the forefoot region (a = .05). RESULTS:
      Significant differences in peak pressure, contact area, and contact time existed
      between the movement tasks when examining the entire foot. In addition,
      significant differences in the force-time integral and peak pressure in the
      forefoot existed between the movement tasks. The force-time integral was highest
      during the side cut in the medial forefoot, hallux, and the lesser toes, while
      the force-time integral was highest during the crossover cut in the middle
      forefoot and the lateral forefoot. Similarly, the peak pressure was highest
      during the side cut in the medial forefoot, hallux, and the lesser toes, while
      peak pressure was highest in the middle forefoot during the acceleration task and
      highest in the lateral forefoot during the crossover-cutting task. CONCLUSIONS:
      The results of this study demonstrated that the crossover cut places an increased
      load on the lateral portion of the forefoot, while the side-cut task places an
      increased load on the medial portion of the forefoot and the acceleration task
      places increased load on the middle forefoot. CLINICAL RELEVANCE: The differences
      in loading patterns based on athletic task are important for understanding
      potential injury mechanisms. In addition, this information could be important for
      defining a return to play protocol for athletes who have had specific injuries.

PMID- 17218654
TI  - Biomechanical analysis of femoral tunnel pull-out angles for anterior cruciate
      ligament reconstruction with bioabsorbable and metal interference screws.
AB  - BACKGROUND: Fixation strength of metal and bioabsorbable interference screws has
      not been evaluated while varying the anterior cruciate ligament graft tension
      angle. HYPOTHESIS: There is no difference in fixation strength between 2 types of
      interference screws for anterior cruciate ligament graft fixation while the graft
      tension angle is varied relative to the femoral tunnel. STUDY DESIGN: Controlled
      laboratory study. METHODS: Forty-eight anterior cruciate ligament reconstructions
      were performed using immature porcine femurs stripped of soft tissue and doubled
      over porcine flexor digitorum profundus tendon grafts. Specimens were randomized
      to bioabsorbable or titanium interference screw fixation. Specimens were
      randomized to one of three pull angles (0 degrees , 30 degrees , 60 degrees )
      representing loading at different knee flexion angles (n = 8/group).
      Reconstructed ligaments were tensioned to 10 N followed by 200 loading cycles
      between 10 and 150 N and a final failure test. Construct elongation (mm) at 100
      and 200 cycles and failure load (N) were analyzed using a 2-way analysis of
      variance (P < .05). RESULTS: Screw material interacted significantly with graft
      tension angle, as the bioabsorbable screw specimens demonstrated significantly
      greater fixation strength when tensioned at greater angles. Specimens fixed with
      bioabsorbable screws showed significantly less elongation at both 100 and 200
      cycles and significantly greater failure load compared with titanium screws.
      CONCLUSION: Bioabsorbable interference screws acutely have increased fixation
      strength compared with titanium interference screws for anterior cruciate
      ligament grafts loaded at greater tension angles. CLINICAL RELEVANCE: The
      strength of anterior cruciate ligament reconstruction fixation increases with
      increasing divergence between the tension angle and femoral tunnel, a condition
      seen when the knee approaches full extension.

PMID- 17218655
TI  - Axillary artery aneurysm with distal embolization in a major league baseball
      pitcher.

PMID- 17218657
TI  - Stress distribution in the supraspinatus tendon after tendon repair: suture
      anchors versus transosseous suture fixation.
AB  - BACKGROUND: The stress concentration at the site of supraspinatus tendon repair,
      either by suture anchor fixation or by transosseous suture fixation, has not been
      fully clarified. HYPOTHESIS: Suture anchor fixation showed higher stress
      concentrations in the tendon than did transosseous suture fixation. STUDY DESIGN:
      Controlled laboratory study. METHODS: Three finite element models were developed
      based on a previously published model of normal supraspinatus tendon (0 degrees
      abduction). Single-row fixation, double-row fixation, and transosseous suture
      fixation were simulated. A tensile force was applied to the proximal end of the
      supraspinatus tendon to simulate its contraction force. RESULTS: In the single
      row model, the stress appeared from the site of the anchor and extended into the
      proximal tendon. The highest stress concentration was observed on the bursal
      surface of the tendon. The double-row model showed a similar pattern to the
      single-row model except that the stress concentration was observed only around
      the medial anchor. In the transosseous model, the stress appeared from the
      attachment site to a bony trough, which extended proximally into the tendon
      substance. No significant stress concentration was observed inside the tendon.
      CONCLUSION: Both single-row and double-row fixations showed higher stress
      concentration inside the tendon than did transosseous suture fixation. CLINICAL
      RELEVANCE: A high stress concentration might be a cause of the rerupture often
      observed after arthroscopic cuff repair using suture anchors.

PMID- 17218656
TI  - Bone morphogenetic proteins-signaling plays a role in tendon-to-bone healing: a
      study of rhBMP-2 and noggin.
AB  - BACKGROUND: Successful anterior cruciate ligament reconstruction requires secure
      healing between tendon and bone. HYPOTHESIS: Bone morphogenetic protein-signaling
      plays an important role in tendon-to-bone healing. rhBMP-2, a powerful
      osteoinductive agent, can improve tendon-bone interdigitation. STUDY DESIGN:
      Controlled laboratory study. METHODS: The study was designed in 2 phases: Phase I
      consisted of a dose-response study where 21 New Zealand White rabbits underwent
      bilateral anterior cruciate ligament reconstructions. Rabbits received either
      rhBMP-2 (11.5, 50, or 115 microg) or noggin (10, 15, 30, or 100 ng) (a potent
      bone morphogenetic proteins inhibitor) delivered in an injectable calcium
      phosphate matrix. Animals were sacrificed at 2 weeks and histomorphometric
      analyses were performed. In phase II, 60 rabbits underwent bilateral anterior
      cruciate ligament reconstructions and were assigned to 3 groups: rhBMP-2 (115
      microg), noggin (30 ng) in a calcium phosphate carrier, and calcium phosphate
      carrier alone. Animals were sacrificed at 2, 4, and 8 weeks and histomorphometric
      and biomechanical analyses were performed. RESULTS: rhBMP-2 treatment led to a
      significant increase in the width of new bone formation at the tendon-bone
      interface in a dose-dependent fashion (0.24-0.35 mm vs 0.13-0.16 mm in controls).
      All dosages of noggin inhibited new bone formation (0.06-0.1 mm vs 0.15-0.16 mm
      in controls); however, there was no dose-dependent effect in the concentrations
      studied. In the phase II study, rhBMP-2 resulted in a significant increase in new
      bone formation (81%, 89%, and 113%) at increasing time periods compared with
      controls. Tunnel diameters in the rhBMP-2 group were significantly smaller (15%
      45%) than in the carrier group. The negative effect of noggin was not sustained,
      as new bone formation increased with time. The rhBMP-2 group demonstrated
      significantly increased stiffness at 8 weeks, while there was no significant
      difference in ultimate tensile load when compared with the other 2 groups.
      CONCLUSION: rhBMP-2 demonstrated a strong, positive dose-dependent effect on
      osteointegration at the tendon-bone junction. In contrast, noggin decreased
      osteointegration. No tunnel widening was detected with rhBMP-2 using the calcium
      phosphate carrier. CLINICAL RELEVANCE: Further studies are needed to investigate
      the potential clinical application of enhancing healing and decreasing recovery
      time using bone morphogenetic proteins in soft tissue ligament reconstruction.

PMID- 17218658
TI  - Soft tissue tendon graft fixation in serially dilated or extraction-drilled
      tibial tunnels: a porcine model study using high-resolution quantitative
      computerized tomography.
AB  - BACKGROUND: Tibial tunnel preparation may contribute to improved soft tissue
      graft fixation. HYPOTHESIS: Step dilation produces greater tunnel wall bone
      volume than does extraction drilling and increases fixation strength.
      Bioabsorbable interference screw divergence decreases fixation strength,
      regardless of tunnel preparation method. STUDY DESIGN: Controlled laboratory
      study. METHODS: Twenty porcine tibias were divided into 2 groups of 10 with
      matching mean apparent bone mineral density. One group received 9-mm-diameter
      extraction-drilled tunnels, and the other group received 7-mm-diameter extraction
      drilled tunnels followed by step dilation to 9 mm. High-resolution quantitative
      computerized tomography scans and voxel analysis techniques determined tunnel
      wall bone volume fraction. Screws secured 8.5-mm-diameter porcine grafts in the
      tunnels. Repeat scans were used to determine screw divergence. Cyclic loading was
      performed in a servohydraulic device before load to failure testing. RESULTS: The
      step dilation group had greater tunnel wall bone volume/total volume than did the
      extraction drilled group; however, a significant increase in fixation strength
      was not detected. Specimens with screw divergence angles less than 15 degrees had
      superior fixation and insertion torques compared with specimens with angles 15
      degrees or more. Screw divergence correlated more strongly with fixation strength
      than did mean apparent bone mineral density or screw insertion torque.
      CONCLUSION: Step dilation increased tunnel wall bone volume/total volume, but
      fixation strength did not improve. Screw divergence >or=15 degrees decreases
      graft-bone tunnel fixation whether or not step dilation is performed. CLINICAL
      RELEVANCE: Screw alignment plays a greater role in anterior cruciate ligament
      graft fixation than does extraction drilling or step dilation tunnel preparation
      methods in healthy bone.

PMID- 17218660
TI  - Ankle sprain injuries and risk factors in amateur soccer players during a 2-year
      period.
AB  - BACKGROUND: Although ankle sprains are common in soccer, the role of various risk
      factors in amateur soccer players is unclear. PURPOSE: To identify the incidence
      of ankle sprain injuries, associated time loss of participation, and risk factors
      during two consecutive seasons in amateur players. STUDY DESIGN: Descriptive
      epidemiology study. METHODS: Of 336 athletes enrolled in the study, 312 male
      amateur soccer players were observed during a 2-year period. Ankle sprain injury
      incidents, participation time loss, injury mechanisms, ankle region injured, and
      other risk factors were recorded in games and practice sessions using
      questionnaires. RESULTS: During the study 208 ankle injuries were recorded, of
      which 139 were ankle sprains. These led to 975 sessions lost (on average, 7 lost
      sessions per injury). Most incidents (80.6%) were contact injuries, occurring
      mostly in defenders. Injury rates were equal between games and practice, while
      61.1% of injuries were observed toward the end of each half of the game (P <
      .05). The injury incidence rate was higher during the first 2 months of the
      season as opposed to the last month (P < .05). Multinomial logistic regression
      showed that previous ankle sprain (P < .05) is a significant predictor of ankle
      sprain injury. CONCLUSION: Ankle sprain injuries in amateur soccer players are
      primarily contact injuries, occurring mainly in defenders and during both games
      and practice. It appears that more injuries occur in players with previous ankle
      injury. Injury rates are higher toward the end of a game and chiefly occur during
      the first 2 months of the season.

PMID- 17218661
TI  - A prospective randomized study of anterior cruciate ligament reconstruction: a
      comparison of patellar tendon and quadruple-strand semitendinosus/gracilis
      tendons fixed with bioabsorbable interference screws.
AB  - BACKGROUND: Debate exists regarding the optimal graft for anterior cruciate
      ligament reconstruction. Few studies have compared the differences in outcome
      after reconstruction using similar fixation methods. HYPOTHESIS: Similar outcomes
      will be seen after anterior cruciate ligament reconstruction with bone-patellar
      tendon-bone or quadruple-strand semitendinosus/gracilis tendons fixed with
      bioabsorbable interference screws. STUDY DESIGN: Randomized controlled trial;
      Level of evidence, 1. METHODS: Ninety-nine patients were prospectively randomized
      to bone-patellar tendon-bone (46 patients) or quadruple-strand
      semitendinosus/gracilis (53 patients) reconstruction groups. The bone-patellar
      tendon-bone group had slightly lower preinjury Tegner scores (6.7 vs 7.1, P =
      .03); otherwise, the groups were similar. All surgeries were performed by a
      single surgeon using an endoscopic technique with bioabsorbable interference
      screw fixation. Patients were evaluated at 3, 6, 12, and 24 months. RESULTS:
      Forty-six bone-patellar tendon-bone and 50 quadruple-strand
      semitendinosus/gracilis patients were available at 24 months (97%). No
      differences in International Knee Documentation Committee grade, Lysholm score,
      Tegner activity level, range of motion, single-legged hop test, KT-1000
      arthrometer manual maximum difference, Short Form-36, or patient knee rating were
      found. The bone-patellar tendon-bone group had better flexion strength in the
      operated leg than in the nonoperated leg (102% vs 90%, P = .0001), fewer patients
      complaining of difficulty jumping (3% vs 17%, P = .03), and a greater number of
      patients returning to preinjury Tegner level (51% vs 26%, P = .01). The quadruple
      strand semitendinosus/gracilis group had better extension strength in the
      operated leg than in the nonoperated leg (92% vs 85%, P = .04), fewer patients
      with sensory deficits (14% vs 83%, P = .0001), and fewer patients with difficulty
      kneeling (6% vs 20%, P = .04). Both groups showed significant improvement in KT
      1000 arthrometer manual maximum difference, Lysholm score, Tegner activity level,
      International Knee Documentation Committee grade, and patient knee rating score.
      CONCLUSIONS: Good outcomes were seen in both the bone-patellar tendon-bone and
      quadruple-strand semitendinosus/gracilis groups. Subtle differences were noted
      between the groups, which may help guide optimal graft choice.

PMID- 17218659
TI  - Effects of initial graft tension on the tibiofemoral compressive forces and joint
      position after anterior cruciate ligament reconstruction.
AB  - BACKGROUND: The initial tension applied to an anterior cruciate ligament graft at
      the time of fixation modulates knee motion and the tibiofemoral compressive
      loads. PURPOSE: To establish the relationships between initial graft tension,
      tibiofemoral compressive force, and the neutral tibiofemoral position in the
      cadaveric knee. STUDY DESIGN: Controlled laboratory study. METHODS: The
      tibiofemoral compressive forces and joint positions were determined in the
      anterior cruciate ligament-intact knee at 0 degrees , 20 degrees , and 90 degrees
      of knee flexion. The anterior cruciate ligament was excised and reconstructed
      with a patellar tendon graft using graft tensions of 1, 15, 30, 60, and 90 N
      applied at 0 degrees , 20 degrees , and 90 degrees of knee flexion. The
      compressive forces and neutral positions were compared between initial tension
      conditions and the anterior cruciate ligament-intact knee. RESULTS: Increasing
      initial graft tension increased the tibiofemoral compressive forces. The forces
      in the medial compartment were 1.8 times those in the lateral compartment. The
      compressive forces were dependent on the knee angle at which the tension was
      applied. The greatest compressive forces occurred when the graft was tensioned
      with the knee in extension. An increase in initial graft tension caused the tibia
      to rotate externally compared with the anterior cruciate ligament-intact knee
      (1.5 degrees and 7.7 degrees of external rotation when tensioned to 90 N at 0
      degrees and 90 degrees of knee flexion, respectively). Increases in initial graft
      tension also caused a significant posterior translation of the tibia relative to
      the femur (0.9 and 5.3 mm of posterior translation when tensioned to 90 N at 0
      degrees and 90 degrees of knee flexion, respectively). CONCLUSION: Different
      initial graft tension protocols produced predictable changes in the tibiofemoral
      compressive forces and joint positions. CLINICAL RELEVANCE: The tibiofemoral
      compressive force and neutral joint position were best replicated with a low
      graft tension (1-15 N) when using a patellar tendon graft.

PMID- 17218662
TI  - Ethics in sports medicine.
AB  - Physicians have struggled with the medical ramifications of athletic competition
      since ancient Greece, where rational medicine and organized athletics originated.
      Historically, the relationship between sport and medicine was adversarial because
      of conflicts between health and sport. However, modern sports medicine has
      emerged with the goal of improving performance and preventing injury, and the
      concept of the "team physician" has become an integral part of athletic culture.
      With this distinction come unique ethical challenges because the customary
      ethical norms for most forms of clinical practice, such as confidentiality and
      patient autonomy, cannot be translated easily into sports medicine. The
      particular areas of medical ethics that present unique challenges in sports
      medicine are informed consent, third parties, advertising, confidentiality, drug
      use, and innovative technology. Unfortunately, there is no widely accepted code
      of sports medicine ethics that adequately addresses these issues.

PMID- 17218663
TI  - High-throughput liberation of water-soluble yeast content by irreversible
      electropermeation (HT-irEP).
AB  - The article describes a high-throughput method for the liberation of water
      soluble cell contents by exploiting the phenomenon of irreversible membrane
      electropermeation (HT-irEP). The method is exemplified in recombinant proteins
      and plasmid liberation from yeast Saccharomyces cerevisiae on the detectable
      level. Obtained extracts are pure enough to be readily applied for further
      analytical analysis such as enzyme assay, PCR, and so on. From the same HT-irEP
      extract, one can measure activity of the target protein and perform amplification
      of the corresponding gene from the DNA vector by PCR for recombinant protein with
      intracellular expression. Therefore, the method is suitable for the high
      throughput screening (HTS) of yeast libraries where extracellular expression of
      recombinant protein is problematic. The method can be easily automated and
      integrated into existing HTS systems.

PMID- 17218664
TI  - Automated multiple ligand screening by frontal affinity chromatography-mass
      spectrometry (FAC-MS).
AB  - High-throughput screening (HTS) efforts to discover "hits" typically rely on the
      large-scale parallel screening of individual compounds with attempts to screen
      mixtures of compounds typically and, unfortunately, giving rise to false
      positives and false negatives due to the nature of the HTS readout (%
      inhibition/activation above a defined threshold) that makes deconvolution
      virtually intractable. Bioaffinity screening methods have emerged as an
      alternative or orthogonal method to classic HTS. One of these methods, frontal
      affinity chromatography coupled to mass spectrometry detection (FAC-MS), although
      still a relatively new technique, is turning out to be a viable screening tool.
      However, to push FAC-MS more to the forefront as a moderate primary HTS system
      (or a secondary screening assay), automation needs to be addressed. An automated
      FAC-MS system is described using 2 columns containing immobilized hERbeta,
      whereby while 1 column is being regenerated, the other is being used. The authors
      are extrapolating that in a continuous 24-h operation, the number of ligands
      screened could potentially approach 10,000. In addition, preliminary structure
      activity relationship binding information (typically not seen in early primary
      HTS) can be obtained by observing the rank order of the library members in the
      various mixtures.

PMID- 17218666
TI  - Alternative statistical parameter for high-throughput screening assay quality
      assessment.
AB  - High-throughput screening is an essential process in drug discovery. The ability
      to identify true active compounds depends on the high quality of assays and
      proper analysis of data. The Z factor, presented by Zhang et al. in 1999,
      provides an easy and useful summary of assay quality and has been a widely
      accepted standard. However, as data analysis has undergone much improvement
      recently, the assessment of assay quality has not evolved in parallel. In this
      article, the authors study the implications of Z factor values under different
      conditions and link the Z factor with the power of discovering true active
      compounds. They discuss the different interpretations of Z factor depending on
      error distributions and advocate direct analysis of power as assay quality
      assessment. They also propose that in estimating assay quality parameters,
      adjustments in data analysis should be taken into account. Studying the power of
      identifying true "hits" gives a more direct interpretation of assay quality and
      may provide guidance in assay optimization on some occasions.

PMID- 17218665
TI  - Drug-membrane interactions studied in phospholipid monolayers adsorbed on
      nonporous alkylated microspheres.
AB  - Characterization of interactions with phospholipids is an integral part of the in
      vitro profiling of drug candidates because of the roles the interactions play in
      tissue accumulation and passive diffusion. Currently used test systems may
      inadequately emulate the bilayer core solvation properties (immobilized
      artificial membranes [IAM]), suffer from potentially slow transport of some
      chemicals (liposomes in free or immobilized forms), and require a tedious
      separation (if used for free liposomes). Here the authors introduce a well
      defined system overcoming these drawbacks: nonporous octadecylsilica particles
      coated with a self-assembled phospholipid monolayer. The coating mimics the
      structure of the headgroup region, as well as the thickness and properties of the
      hydrocarbon core, more closely than IAM. The monolayer has a similar transition
      temperature pattern as the corresponding bilayer. The particles can be separated
      by filtration or a mild centrifugation. The partitioning equilibria of 81 tested
      chemicals were dissected into the headgroup and core contributions, the latter
      using the alkane/water partition coefficients. The deconvolution allowed a
      successful prediction of the bilayer/water partition coefficients with the
      standard deviation of 0.26 log units. The plate-friendly assay is suitable for
      high-throughput profiling of drug candidates without sacrificing the quality of
      analysis or details of the drug-phospholipid interactions.

PMID- 17218667
TI  - Incident reporting and patient safety.

PMID- 17218668
TI  - Protection of sex workers.

PMID- 17218670
TI  - Chronic hepatitis C.

PMID- 17218669
TI  - Preventing falls in elderly people living in hospitals and care homes.

PMID- 17218671
TI  - Food and Drug Administration.

PMID- 17218672
TI  - Mental Health Act: what not to learn from devolution.

PMID- 17218673
TI  - Stent thrombosis: consider also low response to antiplatelets.

PMID- 17218674
TI  - Stent thrombosis: patient card on discontinuing clopidogrel is available.

PMID- 17218675
TI  - Stent thrombosis: antiplatelets alone won't do the job.

PMID- 17218676
TI  - Careers advice: paper is essential reading for the tall and beautiful.

PMID- 17218677
TI  - Umbrella test: urethral dilator is real enough.

PMID- 17218679
TI  - Drug company seeks to suppress internal memos.

PMID- 17218678
TI  - Traumatised refugees: refugee status--a yellow flag in managing back pain.

PMID- 17218680
TI  - Medical emergencies in conflict areas are too often ignored, says aid agency.

PMID- 17218681
TI  - Andrew Wakefield drops libel case against Channel 4.

PMID- 17218686
TI  - German health reforms hang in the balance.

PMID- 17218682
TI  - New WHO chief urges member states to step up efforts for flu pandemic.

PMID- 17218687
TI  - German doctors threaten to boycott patient record project.

PMID- 17218688
TI  - Drug makers end free lunches.

PMID- 17218689
TI  - A wind of change from the west.

PMID- 17218690
TI  - Italian authorities deny that climate change has brought malaria back to its
      shores.

PMID- 17218691
TI  - More cases of polonium-210 contamination are uncovered in London.

PMID- 17218707
TI  - Putting the public at the heart of the NHS.

PMID- 17218708
TI  - Fat chance of hitting obesity targets.

PMID- 17218709
TI  - Ashley X: a difficult moral choice.

PMID- 17218711
TI  - Should Muslims have faith based health services?

PMID- 17218712
TI  - Should Muslims have faith based health services?

PMID- 17218713
TI  - When should antiretroviral therapy for HIV be started?

PMID- 17218714
TI  - Review of stroke rehabilitation.

PMID- 17218715
TI  - Cases in primary care laboratory medicine: testing pitfalls and summary of
      guidance on sex hormone testing.

PMID- 17218716
TI  - What is heterogeneity and is it important?

PMID- 17218717
TI  - Effects of treatment with a combined maxillary protraction and chincap appliance
      in skeletal Class III patients with different vertical skeletal morphologies.
AB  - Several cephalometric studies and case reports have described the effects of
      treatment with a maxillary protraction appliance (MPA) and chincap appliance. The
      purpose of this investigation was to identify differences in the response to
      treatment with a combined MPA and chincap in skeletal Class III patients with
      different vertical skeletal morphologies: short- (low mandibular plane angle) and
      long- (high mandibular plane angle) face types. The cephalograms used in this
      study were of 42 Japanese girls at the beginning of treatment (T0, mean age 10.1
      years) and at removal of the appliance (T1, mean age 11.5 years). The subjects
      were divided into two groups (short and long face) according to the inclination
      of the mandibular plane at T0. Total anterior face height, upper and lower face
      height, occlusal plane, and gonial angle were significantly larger in the long
      face group at T0. In both groups, significant increases in SNA, maxillary size
      (A'-Ptm'), and ANB were noted during treatment. Compared with the long-face
      group, the short-face group showed greater forward displacement and size
      increment of the maxillary body, while there were no significant differences in
      changes in mandibular size or position between the two groups. These results
      indicate that the vertical dimensions of the craniofacial skeleton are important
      factors in the orthopaedic effects of a MPA and chincap and the prognosis for
      skeletal Class III patients.

PMID- 17218718
TI  - Cervical spine curvature and craniofacial morphology in an adult Caucasian group:
      a multiple regression analysis.
AB  - The aim of this study was to investigate the relationship between cervical
      curvature and skeletal facial morphology. Pre-treatment lateral cephalograms in
      natural head position were obtained from 98 orthodontic adult subjects (56 males
      and 42 females; mean age = 31.5 years, standard deviation +/-5.8 years). The
      amount of concavity of the cervical curvature was calculated by a second-order
      quadratic interpolation of the most infero-posterior points of the bodies of the
      seven cervical vertebrae on the radiographs. Linear regression with stepwise
      elimination was carried out to evaluate the sagittal and vertical craniofacial
      dimensions. The results revealed that the amount of curvature was related to (1)
      the horizontal position of the upper incisors with respect to the maxillary and
      mandibular skeletal bases and (2) the sagittal millimetric dimension of the
      maxillary base. These cephalometric variables explained 51 per cent of the total
      variance of cervical curvature. There was no significant correlation between
      cervical curvature and any other cephalometric variable. Cervical curvature was
      not influenced by age or gender.

PMID- 17218719
TI  - Three-dimensional finite-element analysis of maxillary protraction with and
      without rapid palatal expansion.
AB  - The aims of this study were to determine the reaction of the craniofacial bones
      on the protraction force transferred to the maxillary body, and whether or not
      the midpalatal suture had opened during skeletal Class III treatment. A
      computerized tomograph was obtained from a dry skull with a normal occlusion to
      construct a three-dimensional finite-element model (3D.FEM) of the craniofacial
      bones and the maxillary teeth to simulate actual bone reactions. A protraction
      force of 500 g was applied at the first premolar region, directed 20 degrees
      inferior to the occlusal plane. The displacement and the stress distribution of
      the craniofacial bones and sutures were then calculated using the ANSYS 5.3
      program dividing the analysis into two simulations, based on whether or not the
      midpalatal suture was opened. The results showed that there was less compressive
      stress and greater tensile stress in the circumaxillary suture areas when the
      midpalatal suture was opened. The amount of displacement and deformation when the
      midpalatal suture was opened also demonstrated a decrease in upward-forward
      rotation of the maxilla and zygomatic arch and greater amounts of displacement in
      the frontal, vertical, and lateral directions compared with no opening of the
      midpalatal suture. Analysis of these results showed that maxillary protraction
      produce similar changes to normal downward and forward growth of the maxilla and
      was achieved with accompanying opening of the midpalatal suture.

PMID- 17218720
TI  - The endocrine system in chronic nitric oxide deficiency.
AB  - The experimental model of chronic inhibition of nitric oxide (NO) production has
      proven to be a useful tool to study cardiovascular and renal lesions produced by
      this type of hypertension, which are similar to those found in human
      hypertension. It also offers a unique opportunity to study the interaction of NO
      with the humoral systems, known to have a role in the normal physiology of
      vascular tone and renal function. This review provides a thorough and updated
      analysis of the interactions of NO with the endocrine system. There is special
      focus on the main vasoactive factors, including the renin-angiotensin-aldosterone
      system, catecholamines, vasopressin, and endothelin among others. Recent
      discoveries of crosstalk between the endocrine system and NO are also reported.
      Study of these humoral interactions indicates that NO is a molecule with
      ubiquitous function and that its inhibition alters virtually to all other known
      regulatory systems. Thus, hypothyroidism attenuates the pressor effect of NO
      inhibitor N-nitro-L-arginine methyl ester, whereas hyperthyroidism aggravates the
      effects of NO synthesis inhibition; the sex hormone environment determines the
      blood pressure response to NO blockade; NO may play a homeostatic role against
      the prohypertensive effects of mineralocorticoids, thyroid hormones and insulin;
      and finally, NO deficiency affects not only blood pressure but also glucose and
      lipid homeostasis, mimicking the human metabolic syndrome X, suggesting that NO
      deficiency may be a link between metabolic and cardiovascular disease.

PMID- 17218721
TI  - Short-term hypothyroidism after Levothyroxine-withdrawal in patients with
      differentiated thyroid cancer: clinical and quality of life consequences.
AB  - Acute hypothyroidism induced by thyroid hormone withdrawal in patients with
      differentiated thyroid cancer during monitoring for remnant or metastatic
      disease, seriously affects multiple organs and systems, and especially in severe
      cases can impair quality of life. Indeed, it may induce untoward cardiovascular
      effects and can be hazardous in patients with underlying cardiovascular disease,
      particularly in the elderly. Moreover, acute hypothyroidism deranges the lipid
      profile and exacerbates neuropsychiatric illness. The introduction of recombinant
      human TSH (rhTSH) as a diagnostic and therapeutic tool in the care of patients
      with thyroid cancer has widened the scope of disease management. The use of rhTSH
      prevents derangement of various systems at approximately equivalent societal
      costs to that of withdrawal and promotes compliance while preserving the
      patient's normal daily functioning and productivity. Its reliability allied with
      its safety render this compound a valid alternative in the monitoring of patients
      with differentiated thyroid carcinoma as well as providing an alternative
      therapeutic procedure whenever LT4-withdrawal may be hazardous or in cases of
      patient non-compliance.

PMID- 17218722
TI  - Familial adrenocorticotropin-independent macronodular adrenal hyperplasia with
      aberrant serotonin and vasopressin adrenal receptors.
AB  - ACTH-independent macronodular adrenocortical hyperplasia (AIMAH) is rare and
      generally presents as a sporadic disease. We describe a familial case of AIMAH
      with in vivo and in vitro demonstration of aberrant 5-HT4 and vasopressin adrenal
      receptors. Two sisters presented with clinical and biological features of mild
      Cushing's syndrome with bilateral macronodular adrenal enlargement on
      computerized tomography (CT)-scan evaluation. In vivo pharmacological tests
      showed a significant increase in plasma cortisol after terlipressin and
      metoclopramide administration. Unilateral adrenalectomy was performed in one of
      these patients. Reverse transcriptase-PCR analysis of the hyperplastic tissue
      revealed expression of 5-HT4 receptor isoforms (a), (b), (c), (i), and (n), and
      of vasopressin receptors, V1 and V2. Their father and brother were overweight,
      had easy bruisability and presented with biological features of subclinical
      Cushing's syndrome. CT scan showed moderate adrenal enlargement. In vivo
      pharmacological screening tests for the detection of adrenal aberrant receptors
      in the brother were negative. Finally, three out of the two sisters' children
      were evaluated. They had neither clinical nor biological features of Cushing's
      syndrome. Their adrenal glands were normal on CT-scan evaluation. In vivo
      evaluation for the detection of aberrant adrenocortical receptors performed in
      one of these subjects was negative. In conclusion, this study shows that (i)
      familial AIMAH could be an autosomal dominantly inherited disorder; (ii) aberrant
      5-HT4 serotonin and vasopressin receptors can be expressed in familial AIMAH; and
      (iii) phenotypic expression of familial AIMAH could be varied in a same family
      and more pronounced in female than in male patients.

PMID- 17218723
TI  - Treatment of Graves' disease and associated ophthalmopathy with the anti-CD20
      monoclonal antibody rituximab: an open study.
AB  - INTRODUCTION: Hyperthyroid Graves' disease (GD) is a B-cell-mediated condition
      caused by TSH receptor antibodies (TRAb), which decline when GD remits. Anti-CD20
      monoclonal antibody rituximab (RTX) induces transient B-cell depletion that may
      potentially modify the active inflammatory phase of thyroid-associated
      ophthalmopathy (TAO). METHODS: Nine patients with GD, (seven with active TAO, two
      with mild lid signs) were studied. The trial was only approved as an open pilot
      study; thus we compared the effect of RTX therapy to that of i.v. glucocorticoids
      (IVGC) in 20 consecutive patients. Patients were treated with RTX (1000 mg i.v.
      twice at 2-week interval) or with IVGC (500 mg i.v. for 16 weeks). TAO was
      assessed by the clinical activity score (CAS) and severity was classified using
      NOSPECS (No signs or symptoms; Only signs (lid); Soft tissue involvement;
      Proptosis, Extraocular muscle involvement; Corneal involvement; Sight loss).
      Thyroid function and lymphocyte count were measured by standardized methods.
      RESULTS: All patients attained peripheral B-cell depletion with the first RTX
      infusion. Minor side effects were reported in three patients. Thyroid function
      was not affected by RTX therapy and hyperthyroid patients required therapy with
      methimazole. After RTX, the changes in the levels of thyroglobulin antibodies,
      thyroperoxidase antibodies and TRAb were neither significant nor correlated with
      CD20+ depletion (P = NS). CAS values before RTX were 4.7 +/- 0.5 and decreased to
      1.8 +/- 0.8 at the end of follow-up (P < 0.0001) and more significantly compared
      with IVGC (P < 0.05). Proptosis decreased significantly after RTX both in
      patients with active TAO (ANOVA; P < 0.0001) and those with lid signs (ANOVA; P <
      0.003). The degree of inflammation (class 2) decreased significantly in response
      to RTX (ANOVA; P < 0.001). Relapse of active TAO was not observed in patients
      treated with RTX, but occurred in 10% of those treated with IVGC, who also
      experienced adverse effects more frequently (45 vs 33% of patients). CONCLUSIONS:
      RTX positively affects the clinical course of TAO, independently of either
      thyroid function or circulating antithyroid antibodies, including TRAb. If our
      findings are confirmed in large controlled studies, RTX may represent a useful
      therapeutic tool in patients with active TAO.

PMID- 17218724
TI  - A new functional parameter measured at the time of ablation that can be used to
      predict differentiated thyroid cancer recurrence during follow-up.
AB  - BACKGROUND: This study addresses the questions whether patients with a high risk
      for recurrent thyroid cancer can be identified at initial stage, i.e. at the time
      of ablation. METHODS: We evaluated tumor recurrence in consecutive patients
      treated for differentiated thyroid cancer (DTC). Prognostic factors were
      statistically analyzed. We defined prognostic parameters based on thyroglobulin
      (Tg) levels, 24-h I-131 uptake rates and TSH values: (a) Tg/TSH, (b) Tg/24-h I
      131 uptake value, and (c) Tg/(TSHx24-h I-131 uptake). RESULTS: We included 190
      patients (50 male, 140 female; mean age 47 years) with DTC for analysis, 146
      without distant metastases and 44 with M1 tumor stage at initial presentation.
      The mean period of follow-up was 10.4 years (s.d. +/- 3.7 years). In 18 out of
      the 146 DTC patients with M0 disease (12.4%), tumor recurrence was found during
      follow-up. Although tumor stage, age, and standard biochemical values
      significantly differ between patients with and without recurrent disease or
      between patients with M0 and M1 tumor stage, the newly defined parameter
      Tg/(TSHx24-h I-131 uptake) was the best independent significant prognostic
      parameter in the assessment whether patients will develop a tumor recurrence
      during follow-up or not. CONCLUSION: High Tg/(TSHx24-h I-131 uptake) ratios
      justify an adjustment of the I-131 activity for ablation therapy. To assess the
      optimal cut-off value for a dose adjustment, however, further studies are
      required in more patients, but the initial results are encouraging with respect
      to improving outcome in DTC patients.

PMID- 17218725
TI  - Biochemical severity of thyroid ectopia in congenital hypothyroidism demonstrates
      sexual dimorphism.
AB  - BACKGROUND: A recent study suggested that sexual dimorphism affects initial
      thyroid function in congenital hypothyroidism (CH) but differs according to
      aetiology of CH. AIMS: To determine if sexual dimorphism was associated with
      biochemical severity of CH and its aetiology in our large British population.
      METHODS: We examined retrospectively the initial thyroid function tests of 140
      infants diagnosed with CH from screening. All infants underwent Tc-pertechnetate
      radionuclide scans at diagnosis to establish the aetiology of CH prior to
      commencement of treatment. Patients were classified into athyreosis, ectopia and
      presumed dyshormonogenesis on the basis of thyroid scans. A comparison of males
      and females were made within the three aetiological groups for gestational age,
      birth weight, initial dose of levothyroxine (LT4), screening TSH, confirmatory
      plasma thyroxine (T4), confirmatory plasma TSH and age of TSH suppression.
      RESULTS: There was no significant difference between sexes for gestation, birth
      weight and initial treatment dose in all aetiological subgroups. In thyroid
      ectopia, screening TSH and confirmatory plasma TSH were significantly higher in
      females compared with males (P < 0.01), while confirmatory plasma T4 were
      significantly lower in females (P < 0.05). No difference was detected between
      males and females in athyreosis and dyshormonogenesis subgroups for screening
      TSH, confirmatory plasma TSH and total T4. CONCLUSION: Sexual dimorphism
      influenced the biochemical severity of thyroid ectopia in congenital
      hypothyroidism in our British population. However, this effect was not apparent
      in patients with athyreosis or dyshormonogenesis. Further advances in the
      molecular genetics of CH are essential to evaluate this phenomenon further.

PMID- 17218726
TI  - Ten-year GH replacement increases bone mineral density in hypopituitary patients
      with adult onset GH deficiency.
AB  - There are few studies that have determined the effects of long-term GH
      replacement on bone mineral density (BMD) in GH-deficient (GHD) adults. In this
      study, the effects of 10 years of GH replacement on BMD were assessed in 87 GHD
      adults using dual energy X-ray absorptiometry (DEXA). The results show that GH
      replacement induced a sustained increase in BMD at all the skeletal sites
      measured. INTRODUCTION: Little is known of the effect of more than 5 years of GH
      replacement therapy on bone metabolism in GHD adults. PATIENTS AND METHODS: In
      this prospective, open-label, single-center study, which included 87 consecutive
      adults (52 men and 35 women; mean age of 44.1 (range 22-74) years) with adulthood
      onset GHD, the effect of 10 years of GH replacement on BMD was determined.
      RESULTS: The mean initial dose of GH was 0.98 mg/day. The dose was gradually
      lowered and after 10 years the mean dose was 0.47 mg/day. The mean insulin-like
      growth factor-I (IGF-I) SDS increased from 1.81 at baseline to 1.29 at study end.
      The GH replacement induced a sustained increase in total, lumbar (L2-L4) and
      femur neck BMD, and bone mineral content (BMC) as measured by DEXA. The treatment
      response in IGF-I SDS was more marked in men, whereas women had a more marked
      increase in the total body BMC and the total body z-score. There was a tendency
      for women on estrogen treatment to have a larger increase in bone mass and
      density compared with women without estrogen replacement. CONCLUSIONS: Ten years
      of GH replacement in hypopituitary adults induced a sustained, and in some
      variables even a progressive, increase in bone mass and bone density. The study
      results also suggest that adequate estrogen replacement is needed in order to
      have an optimal response in BMD in GHD women.

PMID- 17218727
TI  - Quantitative analysis of somatostatin receptor subtype (SSTR1-5) gene expression
      levels in somatotropinomas and non-functioning pituitary adenomas.
AB  - OBJECTIVE: It is believed that the variable effectiveness of somatostatin analogs
      in post-surgical management of somatotropinomas and non-functioning pituitary
      adenomas (NFPA) may be due in part to variable expression of somatostatin
      receptor isoforms (SSTR1-5), within and between pituitary tumor types. DESIGN AND
      METHODS: Quantitative real-time RT-PCR was used to compare absolute mRNA copy
      numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA. RESULTS:
      Somatostatin receptor subtype 5 mRNA was present at the highest level in
      somatotropinomas, followed by SSTR2>SSTR3>>SSTR1>>>SSTR4. In contrast, SSTR3 mRNA
      was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4,
      and SSTR5 transcripts were only detectable in select tumors. Among
      somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and
      the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide
      long acting repeatable (LAR) (r=0.51 and r=0.66; P=0.05 and P=0.008). Also the
      percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was
      negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was
      positively correlated with SSTR2. CONCLUSIONS: The present report is a large
      series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial
      findings suggest that detailed knowledge of the SSTR mRNA expression profile in
      somatotropinomas can help to predict the hormonal response to therapy with LAR.
      Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3
      preferential or universal ligands such as pasireotide.

PMID- 17218729
TI  - An IGF-I gene polymorphism modifies the risk of developing persistent
      microalbuminuria in type 1 diabetes.
AB  - OBJECTIVE: Derangements of the GH-IGF-I axis have been associated with
      microalbuminuria (MA) in type 1 diabetes. The aim of this study was to
      investigate whether an IGF-I gene promoter polymorphism influenced the
      development of persistent MA in type 1 diabetes. DESIGN: A prospective follow-up
      study of a cohort of 277 patients with newly diagnosed type 1 diabetes
      consecutively enrolled between September 1979 and August 1984. METHODS: Urinary
      albumin excretion rate over 24 h was measured in each patient at least once a
      year. Persistent MA was defined as a urinary albumin excretion rate between 30
      and 300 mg/24 h. RESULTS: During a median follow-up of 18.0 years (range 1.0
      21.5), 79 of 277 patients developed persistent MA. IGF-I gene genotype was
      available for 216 subjects; in 73% of the subjects, the wild-type genotype of
      this IGF-I gene polymorphism was present, while 27% had the variant type. At
      baseline, there were no differences in IGF-I levels and HbA(1c) values between
      subjects with the wild type and subjects with variant type. By Kaplan-Meier
      analysis, subjects with the variant type of this polymorphism had during follow
      up a higher risk of development of MA compared subjects with the wild type (P =
      0.03). CONCLUSIONS: Subjects with the variant type of an IGF-I gene polymorphism
      had a significantly increased risk of developing MA. This risk was not mediated
      through changes in circulating IGF-I levels. Our study suggests that in type 1
      diabetes, this IGF-I gene polymorphism is a risk factor of MA.

PMID- 17218728
TI  - Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical
      practice: safety and efficacy evaluation from the German Pegvisomant
      Observational Study.
AB  - OBJECTIVE: The GH receptor antagonist pegvisomant is a highly effective new
      treatment option in acromegaly. The German Pegvisomant Observational Study (GPOS)
      was started to monitor long-term safety and efficacy of pegvisomant as prescribed
      in clinical practice. DESIGN: GPOS is an observational, multi-center,
      surveillance study, which comprises non-interventional data collection. METHODS:
      Of the 229 patients included in the study, 90.4% had previous pituitary surgery,
      43.2% were treated by radiation therapy, and 94.3% had previous medical therapy
      for acromegaly that had been discontinued mainly due to persistent IGF-I
      elevation or side effects. The intention-to-treat population included 177
      patients with at least one post-baseline efficacy measurement. RESULTS: IGF-I
      levels decreased from 1.75+/-0.91-fold the upper limit of normal at baseline to
      1.05+/- 0.62 at the 6-month visit, 0.96+/-0.60 at the 12-month visit, and to
      0.89+/-0.41-fold after 24 months (P<0.0001). Mean duration of pegvisomant therapy
      was 51.8+/-35.8 weeks (median=51.9 weeks). IGF-I was normalized in 64.4% at 6
      months with a median dose of 15.0 mg/day, in 70.9% at 12 months, and in 76.3% at
      24 months. Fasting glucose levels improved from 114.4+/-45.9 to 101.5+/- 42.8
      mg/dl after 6 months (P<0.01) and to 100.6+/-33.2 mg/ml after 12 months (P<0.01).
      General physical condition measured by specific signs and symptoms score improved
      significantly. Adverse events occurring in >1% were injection site reactions in
      7.4%, elevated liver enzymes (>3 times of normal) in 5.2% (3.1% spontaneously
      normalized during continued treatment), reported increase of pituitary tumor
      volume in 5.2% (which was verified in 3.1%), and headache in 1.7%. CONCLUSIONS:
      Pegvisomant is generally well tolerated with a safety profile similar to that
      reported in clinical trials and can effectively reduce IGF-I in patients with
      acromegaly refractory to conventional therapy.

PMID- 17218730
TI  - Gamma knife radiosurgery is a successful adjunctive treatment in Cushing's
      disease.
AB  - OBJECTIVE: Though transsphenoidal surgery remains the first-line treatment of
      Cushing's disease, recurrence occurs frequently. Conventional radiotherapy and
      anticortisolic drugs both have adverse effects. Stereotactic radiosurgery needs
      to be evaluated more precisely. The aim of this study was to determine long-term
      hormonal effects and tolerance of gamma knife (GK) radiosurgery in Cushing's
      disease. DESIGN: Forty patients with Cushing's disease treated by GK were
      prospectively studied over a decade, with a mean follow-up of 54.7 months. Eleven
      of them were treated with GK as a primary treatment. METHODS: Radiosurgery was
      performed at the Department of Functional Neurosurgery of Marseille, France,
      using the Leksell Gamma Unit B and C models. Median margin dose was 29.5 Gy.
      Patients were considered in remission if they had normalized 24-h free urinary
      cortisol and suppression of plasma cortisol after low-dose dexamethasone
      suppression test. RESULTS: Seventeen patients (42.5%) were in remission after a
      mean of 22 months (range 12-48 months). The two groups did not differ in terms of
      initial hormonal levels. Target volume was significantly higher in uncured than
      in remission group (909.8 vs 443 mm(3), P = 0.038). We found a significant
      difference between patients who were on or off anticortisolic drugs at the time
      of GK (20 vs 48% patients in remission respectively, P = 0.02). CONCLUSION: With
      42% of patients in remission after a median follow-up of 54 months, GK
      stereotactic radiosurgery, especially as an adjunctive treatment to surgery, may
      represent an alternative to other therapeutic options in view of their adverse
      effects.

PMID- 17218731
TI  - Circulating ghrelin levels in girls with central precocious puberty are reduced
      during treatment with LHRH analog.
AB  - Decreased levels of ghrelin have been measured in growing children during
      puberty. No data are available for girls with central precocious puberty (CPP).
      AIMS: To explore ghrelin changes before, during, and after GnRH analog treatment
      in girls with CPP. SUBJECTS AND METHODS: A sample of 20 Caucasian girls (8.08 +/-
      0.65 years of age) with CPP was recruited. Height and weight, bone age, LH, FSH,
      17beta estradiol (E(2)), and ghrelin were measured before starting treatment with
      GnRH analog, 18 months after therapy began and again 6 months after therapy
      discontinuation. RESULTS: LH and E(2) serum levels decreased significantly during
      treatment (2.45 +/- 2.03 vs 0.67 +/- 0.49 UI/l, P < 0.01 and 28.17 +/- 9.7 vs 15
      pmol/l, P < 0.01 respectively), returning to baseline levels after the
      discontinuation of therapy (4.75 +/- 1.66 UI/l and 29.23 +/- 6.99 pmol/l
      respectively). LH peaked following LHRH stimulation significantly (P < 0.01)
      decreased during treatment (24.45 +/- 14.17 vs 1.3 +/- 0.18 UI/l) and then
      increased after therapy discontinuation (12.58 +/- 6.09, P < 0.01). Ghrelin
      decreased significantly (P < 0.05) during treatment (1849 +/- 322 vs 1207 +/- 637
      pg/ml), and increased, though not significantly (P = 0.09) after therapy
      withdrawal (1567 +/- 629 pg/ml). CONCLUSIONS: Contrary to what is expected in
      physiologic puberty, where ghrelin is progressively reduced, the prepubertal
      hormone milieau induced by GnRHa treatment in patients suffering from central
      precocious puberty (CPP) did not promote an increase in ghrelin circulating
      levels. Therefore, in CPP, ghrelin secretion seems to be independent from
      pubertal development per se. Concomitant estrogen suppression during treatment
      may play a potential role in the regulation of ghrelin secretion in these girls.

PMID- 17218732
TI  - Treatment of gonadotropin-deficient boys with recombinant human FSH: long-term
      observation and outcome.
AB  - BACKGROUND: Boys with prepubertal onset of hypogonadotropic hypogonadism (HH) are
      at a risk of poor testis growth and impaired spermatogenesis. One potential cause
      for this is deficient proliferation of immature Sertoli cells before and during
      puberty due to the absence of FSH. OBJECTIVE: To evaluate the effects of
      recombinant human FSH (r-hFSH) and human chorionicgonadotropin (hCG) on
      testicular function and pubertal development in boys with prepubertal onset of
      HH. DESIGN: Retrospective clinical study. SETTING: Two university central
      hospitals, pediatric referral endocrinology outpatient clinics. PATIENTS:
      Fourteen boys (aged, 9.9-17.7 years) with prepubertal (testicular volume (TV) <3
      ml) onset of HH (idiopathic HH, n=2; Kallman syndrome, n=2; idiopathic
      panhypopituitarism, n=4; organic panhypopituitarism, n=6). INTERVENTION:
      Treatment with r-hFSH alone (2 mo-2.8 years) prior to induction of puberty with
      the combination of FSH and hCG. MAIN OUTCOME MEASURES: Progression of puberty,
      change in serum inhibin B, spermatogenesis. RESULTS: r-hFSH alone increased
      testicular volume twofold, from 0.9+/-0.6 ml (mean+/-s.d.) to 1.8 +/- 1.1 ml
      (P<0.005), and serum inhibin B threefold, from 27+/-14 to 80+/-57 pg/ml (P<0.01).
      Three boys with an apparent absence of postnatal hypothalamic-pituitary
      testicular axis activation displayed attenuated inhibin B responses to long-term
      (>or=1 year) r-hFSH (P<0.01). Further significant increase in both TVand inhibin
      B occurred with induction of puberty with FSH and hCG (P<0.001). Seven boys
      provided semen samples: one had azoospermia, and others displayed a maximal sperm
      count range from 2.9 to 92 million/ml (median 8.5 million/ml). CONCLUSIONS: (i) r
      hFSH induces prepubertal testis growth and increases circulating inhibin B
      levels, findings suggesting proliferation of immature Sertoli cells. (ii) Puberty
      was successfully induced with hCG and r-hFSH following r-hFSH priming. (iii)
      Inhibin B appears useful for monitoring spermatogenetic activity in boys treated
      with hCG. (iv) Despite the extremely small initial testis volume, six out of
      seven patients (86%) primed with r-hFSH displayed sperm in the ejaculate
      suggesting beneficial effect of r-hFSH priming on testicular function later in
      life.

PMID- 17218733
TI  - Nocturnal calcium, phosphorus and parathyroid hormone in the diagnosis of
      concealed and subclinical hypoparathyroidism.
AB  - CONTEXT: Circadian rhythms of plasma parathyroid hormone (PTH) show peak values
      at night, whereas serum calcium levels peak in the evening and display a nadir at
      night. HYPOTHESES: Subclinical hypoparathyroidism (HPT) can be detected by
      utilizing the knowledge of diurnal variations. Thalassemia major (TM) may provide
      a model system of subclinical HPT. DESIGN: Nocturnal plasma PTH and serum calcium
      values were determined in 13 TM patients with normal morning serum calcium levels
      as compared with the corresponding values in eight healthy control subjects.
      RESULTS: Six patients with TM presented a nadir serum calcium level of 8.3 mg/dl
      or lower (hypoCa TM) at 0200 h, whereas the remaining seven showed nadir levels
      of 8.4 mg/dl or higher (normoCa TM). Patients with hypoCa TM displayed a drop
      between peak and nadir of 1.2 +/- 0.5 mg/dl as compared with a considerably
      smaller fall of 0.3 +/- 0.7 mg/dl in control subjects (P < 0.05). NormoCa TM
      patients experienced comparable nocturnal variation to that of control subjects.
      Patients from both the hypoCa and normoCa TM groups presented significantly lower
      nocturnal PTH levels than those of control subjects and lost the nocturnal PTH
      variation characteristic of healthy subjects. A plot of all serum calcium against
      plasma PTH levels provides a clear distinction of the three groups. CONCLUSIONS:
      All 13 daytime normocalcemic TM patients presented a certain degree of HPT. The
      hypoCa TM group displayed a concealed HPT detected in all, except the morning
      sampling, whereas normoCa TM patients experienced sub clinical HPT observed in
      the absence of nocturnal HPT variation. Nocturnal measurements of serum minerals
      thus enhance the sensitivity of HPT diagnosis.

PMID- 17218734
TI  - Adiposity, estradiol, and genetic variants of steroid-metabolizing enzymes as
      determinants of bone mineral density.
AB  - OBJECTIVES: Bone mineral density (BMD) is a complex trait resulting from the
      interplay of genetic and acquired factors. The objective of this study was to
      explore the influence of several anthropometric, lifestyle, genetic, and hormonal
      factors on BMD and analyze the possible differences in men and women. METHODS: We
      studied 572 individuals over 50 years of age (381 postmenopausal women and 191
      men). Lumbar spine and femoral neck BMD were measured by dual energy x-ray
      absorptiometry. The free estrogen index (FEI) was calculated as the ratio of
      serum estradiol to sex hormone binding globulin in 241 individuals. Three
      polymorphisms in the genes coding for 17-hydroxylase/liase, sulfotransferase, and
      5alpha-reductase were studied in DNA isolated from blood cells. RESULTS: Body
      mass index was strongly correlated to spine and femoral BMD both in women and in
      men (r = 0.32-0.49; P < 0.001). FEI was also independently correlated with spine
      BMD in both sexes (r = 0.23 and 0.34, P < 0.01), and with femoral neck in women
      (r = 0.30). Women with G alleles of the sulfotransferase gene tended to have
      higher spine BMD than those with C alleles (P = 0.025). No other genotype-related
      differences in BMD were found. CONCLUSIONS: In conclusion, the results of this
      study point toward body weight and estradiol levels as major factors determining
      BMD both in women and in men. A common polymorphism of the sulfotransferase gene
      also appears to be associated to spine BMD in women.

PMID- 17218735
TI  - Bone mineral density and hip structural analysis in type 1 diabetic men.
AB  - OBJECTIVE: The risk of non-vertebral fractures is increased in men with type 1
      diabetes (DM1) but studies have shown only moderately decreased or normal bone
      mineral density (BMD) in these patients. No previous studies have evaluated hip
      strength and geometry indices in DM1 patients. This study was therefore designed
      to characterize associations between BMD, dual X-ray absorptiometry (DXA)-based
      hip strength indices, metabolic control, and DM1chronic complications. DESIGN AND
      METHODS: The study was performed on 36 males aged 43.6 +/- 5.1 years with long
      lasting DM1 and 36 healthy males matched for age, weight, and height. BMD in
      lumbar spine, total hip, upper and lower part of the femoral neck, hip axis
      length, cross-sectional area and moment of inertia (CSMI), and glycated
      hemoglobin (HbA1c) were measured. RESULTS: DM1 men had decreased spine BMD (P <
      0.05) and normal total hip BMD in comparison with controls. Hip geometry and
      strength indices were comparable in both groups. However, M1 men had decreased
      CSMI and upper femur BMD but these differences did not reach statistical
      significance (P = 0.06). BMD changes and hip strength parameters did not
      correlate with HbA1c. CONCLUSIONS: Middle-aged DM1 men have decreased lumbar
      spine BMD, normal hip BMD and normal hip strength indices. These changes are not
      influenced by metabolic control and presence of chronic microvascular
      complications.

PMID- 17218736
TI  - Genetic and environmental determinants of circulating resistin level in a
      community-based sample.
AB  - OBJECTIVE: Resistin is a hormone secreted by adipose tissue, monocytes, bone
      marrow, and other tissues. It was also proclaimed as an important link between
      obesity and diabetes. The main objective of this study was to elucidate the
      contribution of a number of endogenous factors, such as sex, age, obesity
      characteristics, and genetic effects to the production of resistin in apparently
      healthy individuals. We also tested the possible relationships between
      circulating levels of resistin and other adipokines (leptin, interleukin-6 (IL
      6), and tumor necrosis factor-alpha (TNF-alpha)). MEASUREMENTS: The plasma levels
      of studied adipokines were determined by enzyme-linked immunoassay in pedigree
      based sample (n = 616), and subjected to model-based quantitative genetic
      analysis. RESULTS: Resistin levels were significantly higher in women than in men
      (3.60 +/- 2.53 vs 3.15 +/- 2.48 ng/ml, P < 0.001), and varied independently of
      age in either sex. Statistical-genetic analysis revealed significant familial
      correlations (P < 0.01) for resistin. Adjusted for covariates, 66.38 +/- 10.28%
      of the resistin variation was attributable to putative genetic factors. A
      relatively small portion of the resistin variation (11.54 +/- 5.77%) was
      attributable to sharing a common household environment. The remaining variation,
      22.12 +/- 17.69% was due to random environmental (i.e., unmeasured non-additive
      genetic) effects. The results of our analysis showed modest significant
      correlation of resistin with TNF-alpha and IL-6, and only in some groups; thus,
      while resistin was correlated with TNF-alpha in men, the correlation with IL-6
      was significant only in the post-menopausal women group. CONCLUSIONS: Our
      observations indicate that resistin is strongly influenced by genetic factors.
      The high heritability estimates for resistin concentrations clearly suggest the
      continuing need for further molecular genetic investigations.

PMID- 17218737
TI  - Increased preoperative glucose levels are associated with perioperative mortality
      in patients undergoing noncardiac, nonvascular surgery.
AB  - OBJECTIVE: To determine the relationship between preoperative glucose levels and
      perioperative mortality in noncardiac, nonvascular surgery. RESEARCH DESIGN AND
      METHODS: We performed a case-control study in a cohort of 108 593 patients who
      underwent noncardiac surgery at the Erasmus MC during 1991-2001. Cases were 989
      patients who underwent elective noncardiac, nonvascular surgery and died within
      30 days during hospital stay. From the remaining patients, 1879 matched controls
      (age, sex, calendar year, and type of surgery) were selected. Information was
      obtained regarding the presence of cardiac risk factors, medication, and
      preoperative laboratory results. Preoperative random glucose levels <5.6 mmol/l
      (110 mg/dl) were normal. Impaired glucose levels in the range of 5.6-11.1 mmol/l
      were prediabetes. Glucose levels >or=11.1 mmol/l (200 mg/dl) were diabetes.
      RESULTS: Preoperative glucose levels were available in 904 cases and 1247
      controls. A cardiovascular complication was the primary cause of death in 207
      (23%) cases. Prediabetes glucose levels were associated with a 1.7-fold increased
      mortality risk compared with normoglycemic levels (adjusted odds ratio (OR) 1.7
      and 95% confidence interval (CI) 1.4-2.1; P<0.001). Diabetes glucose levels were
      associated with a 2.1-fold increased risk (adjusted OR 2.1 and 95% CI 1.3-3.5;
      P<0.001). In cases with cardiovascular death, prediabetes glucose levels had a
      threefold increased cardiovascular mortality risk (adjusted OR 3.0 and 95% CI 1.7
      5.1) and diabetes glucose levels had a fourfold increased cardiovascular
      mortality risk (OR 4.0 and 95% CI 1.3-12). CONCLUSIONS: Preoperative
      hyperglycemia is associated with increased (cardiovascular) mortality in patients
      undergoing noncardiac, nonvascular surgery.

PMID- 17218738
TI  - Volume splitting and its applications.
AB  - Splitting a volumetric object is a useful operation in volume graphics and its
      applications, but is not widely supported by existing systems for volume-based
      modeling and rendering. In this paper, we present an investigation into two main
      algorithmic approaches, namely, explicit and implicit splitting, for modeling and
      rendering splitting actions. We consider a generalized notion based on scalar
      fields, which encompasses discrete specifications (e.g., volume data sets) as
      well as procedural specifications (e.g., hypertextures) of volumetric objects. We
      examine the correctness, effectiveness, efficiency, and deficiencies of each
      approach in specifying and controlling a spatial and temporal specification of
      splitting. We propose methods for implementing these approaches and for
      overcoming their deficiencies. We present a modeling tool for creating
      specifications of splitting functions, and describe the use of volume scene
      graphs for facilitating direct rendering of volume splitting. We demonstrate the
      use of these approaches with examples of volume visualization, medical
      illustration, volume animation, and special effects.

PMID- 17218739
TI  - Evaluation of a low-cost 3D sound system for immersive virtual reality training
      systems.
AB  - Since Head Mounted Displays (HMD), datagloves, tracking systems, and powerful
      computer graphics resources are nowadays in an affordable price range, the usage
      of PC-based "Virtual Training Systems" becomes very attractive. However, due to
      the limited field of view of HMD devices, additional modalities have to be
      provided to benefit from 3D environments. A 3D sound simulation can improve the
      capabilities of VR systems dramatically. Unfortunately, realistic 3D sound
      simulations are expensive and demand a tremendous amount of computational power
      to calculate reverberation, occlusion, and obstruction effects. To use 3D sound
      in a PC-based training system as a way to direct and guide trainees to observe
      specific events in 3D space, a cheaper alternative has to be provided, so that a
      broader range of applications can take advantage of this modality. To address
      this issue, we focus in this paper on the evaluation of a low-cost 3D sound
      simulation that is capable of providing traceable 3D sound events. We describe
      our experimental system setup using conventional stereo headsets in combination
      with a tracked HMD device and present our results with regard to precision,
      speed, and used signal types for localizing simulated sound events in a virtual
      training environment.

PMID- 17218741
TI  - Image-based color ink diffusion rendering.
AB  - This paper proposes an image-based painterly rendering algorithm for
      automatically synthesizing an image with color ink diffusion. We suggest a
      mathematical model with a physical base to simulate the phenomenon of color
      colloidal ink diffusing into absorbent paper. Our algorithm contains three main
      parts: a feature extraction phase, a Kubelka-Munk (KM) color mixing phase, and a
      color ink diffusion synthesis phase. In the feature extraction phase, the
      information of the reference image is simplified by luminance division and color
      segmentation. In the color mixing phase, the KM theory is employed to approximate
      the result when one pigment is painted upon another pigment layer. Then, in the
      color ink diffusion synthesis phase, the physically-based model that we propose
      is employed to simulate the result of color ink diffusion in absorbent paper
      using a texture synthesis technique. Our image-based ink diffusing rendering
      (IBCIDR) algorithm eliminates the drawback of conventional Chinese ink
      simulations, which are limited to the black ink domain, and our approach
      demonstrates that, without using any strokes, a color image can be automatically
      converted to the diffused ink style with a visually pleasing appearance.

PMID- 17218740
TI  - A survey on hair modeling: styling, simulation, and rendering.
AB  - Realistic hair modeling is a fundamental part of creating virtual humans in
      computer graphics. This paper surveys the state of the art in the major topics of
      hair modeling: hairstyling, hair simulation, and hair rendering. Because of the
      difficult, often unsolved problems that arise in all these areas, a broad
      diversity of approaches are used, each with strengths that make it appropriate
      for particular applications. We discuss each of these major topics in turn,
      presenting the unique challenges facing each area and describing solutions that
      have been presented over the years to handle these complex issues. Finally, we
      outline some of the remaining computational challenges in hair modeling.

PMID- 17218742
TI  - A streaming-based solution for remote visualization of 3D graphics on mobile
      devices.
AB  - Mobile devices such as Personal Digital Assistants, Tablet PCs, and cellular
      phones have greatly enhanced user capability to connect to remote resources.
      Although a large set of applications are now available bridging the gap between
      desktop and mobile devices, visualization of complex 3D models is still a task
      hard to accomplish without specialized hardware. This paper proposes a system
      where a cluster of PCs, equipped with accelerated graphics cards managed by the
      Chromium software, is able to handle remote visualization sessions based on MPEG
      video streaming involving complex 3D models. The proposed framework allows mobile
      devices such as smart phones, Personal Digital Assistants (PDAs), and Tablet PCs
      to visualize objects consisting of millions of textured polygons and voxels at a
      frame rate of 30 fps or more depending on hardware resources at the server side
      and on multimedia capabilities at the client side. The server is able to
      concurrently manage multiple clients computing a video stream for each one;
      resolution and quality of each stream is tailored according to screen resolution
      and bandwidth of the client. The paper investigates in depth issues related to
      latency time, bit rate and quality of the generated stream, screen resolutions,
      as well as frames per second displayed.

PMID- 17218743
TI  - Pose-oblivious shape signature.
AB  - A 3D shape signature is a compact representation for some essence of a shape.
      Shape signatures are commonly utilized as a fast indexing mechanism for shape
      retrieval. Effective shape signatures capture some global geometric properties
      which are scale, translation, and rotation invariant. In this paper, we introduce
      an effective shape signature which is also pose-oblivious. This means that the
      signature is also insensitive to transformations which change the pose of a 3D
      shape such as skeletal articulations. Although some topology-based matching
      methods can be considered pose-oblivious as well, our new signature retains the
      simplicity and speed of signature indexing. Moreover, contrary to topology-based
      methods, the new signature is also insensitive to the topology change of the
      shape, allowing us to match similar shapes with different genus. Our shape
      signature is a 2D histogram which is a combination of the distribution of two
      scalar functions defined on the boundary surface of the 3D shape. The first is a
      definition of a novel function called the local-diameter function. This function
      measures the diameter of the 3D shape in the neighborhood of each vertex. The
      histogram of this function is an informative measure of the shape which is
      insensitive to pose changes. The second is the centricity function that measures
      the average geodesic distance from one vertex to all other vertices on the mesh.
      We evaluate and compare a number of methods for measuring the similarity between
      two signatures, and demonstrate the effectiveness of our pose-oblivious shape
      signature within a 3D search engine application for different databases
      containing hundreds of models.

PMID- 17218744
TI  - Caustics mapping: an image-space technique for real-time caustics.
AB  - In this paper, we present a simple and practical technique for real-time
      rendering of caustics from reflective and refractive objects. Our algorithm,
      conceptually similar to shadow mapping, consists of two main parts: creation of a
      caustic map texture, and utilization of the map to render caustics onto nonshiny
      surfaces. Our approach avoids performing any expensive geometric tests, such as
      ray-object intersection, and involves no precomputation; both of which are common
      features in previous work. The algorithm is well suited for the standard
      rasterization pipeline and runs entirely on the graphics hardware.

PMID- 17218745
TI  - Personality and emotion-based high-level control of affective story characters.
AB  - Human emotional behavior, personality, and body language are the essential
      elements in the recognition of a believable synthetic story character. This paper
      presents an approach using story scripts and action descriptions in a form
      similar to the content description of storyboards to predict specific personality
      and emotional states. By adopting the Abridged Big Five Circumplex (AB5C) Model
      of personality from the study of psychology as a basis for a computational model,
      we construct a hierarchical fuzzy rule-based system to facilitate the personality
      and emotion control of the body language of a dynamic story character. The story
      character can consistently perform specific postures and gestures based on
      his/her personality type. Story designers can devise a story context in the form
      of our story interface which predictably motivates personality and emotion values
      to drive the appropriate movements of the story characters. Our system takes
      advantage of relevant knowledge described by psychologists and researchers of
      storytelling, nonverbal communication, and human movement. Our ultimate goal is
      to facilitate the high-level control of a synthetic character.

PMID- 17218746
TI  - Graph visualization techniques for web clustering engines.
AB  - One of the most challenging issues in mining information from the World Wide Web
      is the design of systems that present the data to the end user by clustering them
      into meaningful semantic categories. We show that the analysis of the results of
      a clustering engine can significantly take advantage of enhanced graph drawing
      and visualization techniques. We propose a graph-based user interface for Web
      clustering engines that makes it possible for the user to explore and visualize
      the different semantic categories and their relationships at the desired level of
      detail.

PMID- 17218747
TI  - TopoLayout: multilevel graph layout by topological features.
AB  - We describe TopoLayout, a feature-based, multilevel algorithm that draws
      undirected graphs based on the topological features they contain. Topological
      features are detected recursively inside the graph, and their subgraphs are
      collapsed into single nodes, forming a graph hierarchy. Each feature is drawn
      with an algorithm tuned for its topology. As would be expected from a feature
      based approach, the runtime and visual quality of TopoLayout depends on the
      number and types of topological features present in the graph. We show
      experimental results comparing speed and visual quality for TopoLayout against
      four other multilevel algorithms on a variety of data sets with a range of
      connectivities and sizes. TopoLayout frequently improves the results in terms of
      speed and visual quality on these data sets.

PMID- 17218748
TI  - Interactive collision detection for deformable models using streaming AABBs.
AB  - We present an interactive and accurate collision detection algorithm for
      deformable, polygonal objects based on the streaming computational model. Our
      algorithm can detect all possible pairwise primitive-level intersections between
      two severely deforming models at highly interactive rates. In our streaming
      computational model, we consider a set of axis aligned bounding boxes (AABBs)
      that bound each of the given deformable objects as an input stream and perform
      massively-parallel pairwise, overlapping tests onto the incoming streams. As a
      result, we are able to prevent performance stalls in the streaming pipeline that
      can be caused by expensive indexing mechanism required by bounding volume
      hierarchy-based streaming algorithms. At runtime, as the underlying models deform
      over time, we employ a novel, streaming algorithm to update the geometric changes
      in the AABB streams. Moreover, in order to get only the computed result (i.e.,
      collision results between AABBs) without reading back the entire output streams,
      we propose a streaming en/decoding strategy that can be performed in a
      hierarchical fashion. After determining overlapped AABBs, we perform a primitive
      level (e.g., triangle) intersection checking on a serial computational model such
      as CPUs. We implemented the entire pipeline of our algorithm using off-the-shelf
      graphics processors (GPUs), such as nVIDIA GeForce 7800 GTX, for streaming
      computations, and Intel Dual Core 3.4G processors for serial computations. We
      benchmarked our algorithm with different models of varying complexities, ranging
      from 15K up to 50K triangles, under various deformation motions, and the timings
      were obtained as 30 approximately 100 FPS depending on the complexity of models
      and their relative configurations. Finally, we made comparisons with a well-known
      GPU-based collision detection algorithm, CULLIDE [4] and observed about three
      times performance improvement over the earlier approach. We also made comparisons
      with a SW-based AABB culling algorithm [2] and observed about two times
      improvement.

PMID- 17218749
TI  - Topology-controlled volume rendering.
AB  - Topology provides a foundation for the development of mathematically sound tools
      for processing and exploration of scalar fields. Existing topology-based methods
      can be used to identify interesting features in volumetric data sets, to find
      seed sets for accelerated isosurface extraction, or to treat individual connected
      components as distinct entities for isosurfacing or interval volume rendering. We
      describe a framework for direct volume rendering based on segmenting a volume
      into regions of equivalent contour topology and applying separate transfer
      functions to each region. Each region corresponds to a branch of a hierarchical
      contour tree decomposition, and a separate transfer function can be defined for
      it. The novel contributions of our work are 1) a volume rendering framework and
      interface where a unique transfer function can be assigned to each subvolume
      corresponding to a branch of the contour tree, 2) a runtime method for adjusting
      data values to reflect contour tree simplifications, 3) an efficient way of
      mapping a spatial location into the contour tree to determine the applicable
      transfer function, and 4) an algorithm for hardware-accelerated direct volume
      rendering that visualizes the contour tree-based segmentation at interactive
      frame rates using graphics processing units (GPUs) that support loops and
      conditional branches in fragment programs.

PMID- 17218750
TI  - Light scattering from filaments.
AB  - Photo realistic visualization of a huge number of individual filaments like in
      the case of hair, fur, or knitwear is a challenging task: Explicit rendering
      approaches for simulating radiance transfer at a filament get totally
      impracticable with respect to rendering performance and it is also not obvious
      how to derive efficient scattering functions for different levels of (geometric)
      abstraction or how to deal with very complex scattering mechanisms. We present a
      novel uniform formalism for light scattering from filaments in terms of radiance,
      which we call the Bidirectional Fiber Scattering Distribution Function (BFSDF).
      We show that previous specialized approaches, which have been developed in the
      context of hair rendering, can be seen as instances of the BFSDF. Similar to the
      role of the BSSRDF for surface scattering functions, the BFSDF can be seen as a
      general approach for light scattering from filaments, which is suitable for
      deriving approximations in a canonic and systematic way. For the frequent cases
      of distant light sources and observers, we deduce an efficient far field
      approximation (Bidirectional Curve Scattering Distribution Function, BCSDF). We
      show that on the basis of the BFSDF, parameters for common rendering techniques
      can be estimated in a non-ad-hoc, but physically-based way.

PMID- 17218751
TI  - A model and framework for visualization exploration.
AB  - Visualization exploration is the process of extracting insight from data via
      interaction with visual depictions of that data. Visualization exploration is
      more than presentation; the interaction with both the data and its depiction is
      as important as the data and depiction itself. Significant visualization research
      has focused on the generation of visualizations (the depiction); less effort has
      focused on the exploratory aspects of visualization (the process). However,
      without formal models of the process, visualization exploration sessions cannot
      be fully utilized to assist users and system designers. Toward this end, we
      introduce the P-Set Model of Visualization Exploration for describing this
      process and a framework to encapsulate, share, and analyze visual explorations.
      In addition, systems utilizing the model and framework are more efficient as
      redundant exploration is avoided. Several examples drawn from visualization
      applications demonstrate these benefits. Taken together, the model and framework
      provide an effective means to exploit the information within the visual
      exploration process.

PMID- 17218754
TI  - Fast animation of lightning using an adaptive mesh.
AB  - We present a fast method for simulating, animating, and rendering lightning using
      adaptive grids. The "dielectric breakdown model" is an elegant algorithm for
      electrical pattern formation that we extend to enable animation of lightning. The
      simulation can be slow, particularly in 3D, because it involves solving a large
      Poisson problem. Losasso et al. recently proposed an octree data structure for
      simulating water and smoke, and we show that this discretization can be applied
      to the problem of lightning simulation as well. However, implementing the
      incomplete Cholesky conjugate gradient (ICCG) solver for this problem can be
      daunting, so we provide an extensive discussion of implementation issues. ICCG
      solvers can usually be accelerated using "Eisenstat's trick," but the trick
      cannot be directly applied to the adaptive case. Fortunately, we show that an
      "almost incomplete Cholesky" factorization can be computed so that Eisenstat's
      trick can still be used. We then present a fast rendering method based on
      convolution that is competitive with Monte Carlo ray tracing but orders of
      magnitude faster, and we also show how to further improve the visual results
      using jittering.

PMID- 17218752
TI  - Fracturing rigid materials.
AB  - We propose a novel approach to fracturing (and denting) brittle materials. To
      avoid the computational burden imposed by the stringent time step restrictions of
      explicit methods or with solving nonlinear systems of equations for implicit
      methods, we treat the material as a fully rigid body in the limit of infinite
      stiffness. In addition to a triangulated surface mesh and level set volume for
      collisions, each rigid body is outfitted with a tetrahedral mesh upon which
      finite element analysis can be carried out to provide a stress map for fracture
      criteria. We demonstrate that the commonly used stress criteria can lead to
      arbitrary fracture (especially for stiff materials) and instead propose the
      notion of a time averaged stress directly into the FEM analysis. When objects
      fracture, the virtual node algorithm provides new triangle and tetrahedral meshes
      in a straightforward and robust fashion. Although each new rigid body can be
      rasterized to obtain a new level set, small shards can be difficult to accurately
      resolve. Therefore, we propose a novel collision handling technique for treating
      both rigid bodies and rigid body thin shells represented by only a triangle mesh.

PMID- 17218753
TI  - Aura 3D textures.
AB  - This paper presents a new technique, called aura 3D textures, for generating
      solid textures based on input examples. Our method is fully automatic and
      requires no user interactions in the process. Given an input texture sample, our
      method first creates its aura matrix representations and then generates a solid
      texture by sampling the aura matrices of the input sample constrained in multiple
      view directions. Once the solid texture is generated, any given object can be
      textured by the solid texture. We evaluate the results of our method based on
      extensive user studies. Based on the evaluation results using human subjects, we
      conclude that our algorithm can generate faithful results of both stochastic and
      structural textures with an average successful rate of 76.4 percent. Our
      experimental results also show that the new method outperforms Wei and Levoy's
      method and is comparable to that proposed by Jagnow et al. [21].

PMID- 17218755
TI  - A framework for holographic scene representation and image synthesis.
AB  - We present a framework for the holographic representation and display of graphics
      objects. As opposed to traditional graphics representations, our approach
      reconstructs the light wave reflected or emitted by the original object directly
      from the underlying digital hologram. Our novel holographic graphics pipeline
      consists of several stages including the digital recording of a full-parallax
      hologram, the reconstruction and propagation of its wavefront, and rendering of
      the final image onto conventional, framebuffer-based displays. The required view
      dependent depth image is computed from the phase information inherently
      represented in the complex-valued wavefront. Our model also comprises a correct
      physical modeling of the camera taking into account optical elements, such as
      lens and aperture. It thus allows for a variety of effects including depth of
      field, diffraction, interference, and features built-in anti-aliasing. A central
      feature of our framework is its seamless integration into conventional rendering
      and display technology which enables us to elegantly combine traditional 3D
      object or scene representations with holograms. The presented work includes the
      theoretical foundations and allows for high quality rendering of objects
      consisting of large numbers of elementary waves while keeping the hologram at a
      reasonable size.

PMID- 17218757
TI  - Physiological and pathological consequences of identification of very small
      embryonic like (VSEL) stem cells in adult bone marrow.
AB  - Bone marrow (BM) contains a population of self-renewing hematopoietic stem cells
      (HSC) that give rise to cells from all hemato-lymphopoietic lineages. The concept
      that HSC could also be plastic and be able to transdifferentiate into
      stem/progenitor cells for different non-hematopoietic tissues became one of the
      most controversial issues of modern stem cell biology. Accumulating experimental
      evidence suggests that contribution of BM-derived stem cells to organ/tissue
      regeneration could be explained not by plasticity (transdifferentiation) of HSC
      but rather by the presence of non-hematopoietic stem cells in BM. In this review
      new evidence will be presented, that adult BM contains a small population of
      pluripotent very small embryonic-like (VSEL) stem cells. These cells are
      deposited in BM early during ontogenesis and could be mobilized from BM and
      circulate in peripheral blood during tissue/organ injury in an attempt to
      regenerate damaged organs. However, if these cells are mobilized at the wrong
      time and migrate to the wrong place they may contribute to the development of
      several pathologies, including tumor formation.

PMID- 17218758
TI  - Melatonin in humans.
AB  - Melatonin, the hormone of the pineal gland, received a great deal of attention in
      the last decade because of its availability as over-the-counter drug or food
      supplement in some countries and suggested role in many vital physiological
      processes. Melatonin secretion is not restricted to mammals but is also produced
      in nonmammalian vertebrates, in some invertebrates, and in many plants, with the
      same molecular structure. The synthesis of melatonin is strictly controlled by
      lighting conditions and shows a clear circadian rhythm with low values during the
      daytime and significant increase at night. In this survey the basic data on
      melatonin significance in human physiology and in pathological processes as well
      as its possible therapeutic significance are reviewed and discussed.

PMID- 17218759
TI  - Nocturnal secretion of melatonin in patients with upper digestive tract
      disorders.
AB  - Recently, the results of many experimental investigations have shown that
      melatonin possesses gastroprotective properties. On the other hand its role in
      pathogenesis of upper digestive tract diseases in man still remains unclear. The
      aim of the study was to investigate nocturnal secretion of melatonin in patients
      with functional and organic diseases of the upper part of digestive tract. The
      investigations were carried out in 149 persons, aged 21-51 years, including
      healthy subjects (group I, n=30), and patients with non-erosive gastroduodenal
      reflux (NERD, group II, n=24), with gastroesophageal reflux disease (GERD, group
      III, n=25), with functional dyspepsia (FD, according to the Rome III Criteria,
      group IV, n=36) and with recurrent duodenal ulcer (DUD, group V, n=34). Diagnoses
      were established on the basis of endoscopic imaging and histological examination,
      24-hour pH-metry and laboratory tests. Melatonin serum concentration was measured
      with ELISA method. Blood samples were taken for examination in red-lighted room
      at 10 p.m. and on the following day at 2 and 6 a.m. The highest concentration of
      melatonin in all examined groups was determined at 2 a.m. The average melatonin
      concentration in healthy subjects was 34,7 +/- 4,8 pg/ml. In patients with GERD
      and DUD melatonin concentration was lower than in healthy subjects - 27,2 +/- 8,5
      pg/ml and 25,5 +/- 6,2 pg/ml respectively (p < 0,05; p < 0,01). The highest
      concentration of melatonin was found in patients with NERD and FD - 43,2 +/- 10,8
      pg/ml and 42,4 +/- 10,1 pg/ml (p < 0,01; p < 0,05). The findings of this study
      support the notion that melatonin exerts beneficial influences on the upper
      digestive tract. It is likely that high or relatively correct secretion of
      melatonin is sufficient to prevent peptic changes in esophageal and duodenal
      mucosa.

PMID- 17218760
TI  - Involvement of Helicobacter pylori infection in neuro-hormonal control of food
      intake.
AB  - Ghrelin and leptin are endogenous peptides that have been implicated in the
      control of food intake, energy homeostasis and body weight gain. Although the
      stomach is the major source of circulating ghrelin and partly contributes also to
      plasma leptin, controversy exists over the influence of gastric Helicobacter
      pylori (Hp) infection on the ghrelin and leptin release. To resolve this
      controversy, plasma immunoreactive ghrelin and leptin levels were determined in
      Hp-positive and Hp negative children (N=60) and in adults (N=120) and daily
      concentrations of these hormones were measured at 2 h intervals before and after
      meals. Serum levels of ghrelin and leptin as well as gastrin were measured by
      RIA. Hp status was assessed using (13)C-urea breath test (UBT) and serology.
      Children with negative UBT showed significantly higher basal serum levels of
      ghrelin and lower concentrations of leptin than those with positive UBT. Adults
      without Hp infection also showed significantly higher fasting serum levels of
      ghrelin and lower levels of leptin than those in Hp infected subjects. In adults,
      especially without Hp infection, plasma levels of ghrelin showed a marked rise
      before the meal and sudden decrease following the food intake, while plasma
      leptin did not showed significant meal-related alterations, but in general its
      level was significantly higher in Hp positive than Hp negative subjects. Serum
      gastrin concentrations were significantly elevated in both Hp positive children
      and adults and these levels were significantly lower in Hp negative subjects. We
      conclude that Hp infection in children and adults causes a marked reduction in
      plasma levels of ghrelin, while increasing plasma levels of leptin and gastrin.
      These alterations in plasma levels of gastric originated appetite-controlling
      hormones in Hp infected children and adults may contribute to the alterations of
      the appetite and dyspeptic symptoms observed in these subjects.

PMID- 17218761
TI  - Ghrelin and melatonin in the regulation of pancreatic exocrine secretion and
      maintaining of integrity.
AB  - Ghrelin and melatonin are produced in the central nervous system and in the
      gastrointestinal tissues; ghrelin in the stomach, and melatonin - in the liver
      and in the intestine. Both ghrelin and melatonin have been reported to protect
      the gastric mucosa against acute lesions and to influence gastrointestinal
      motility and secretions, however the physiological significance of these peptides
      in the gastrointestinal tissues remains unknown. In spite of the presence of
      ghrelin and melatonin receptors in the pancreatic tissue little is known about
      the role of these peptides in the pancreas. It is very likely that both ghrelin
      and melatonin, which are released from the gastrointestinal tract in relation to
      food ingestion, could be implicated in the postprandial stimulation of pancreatic
      enzyme secretion though the activation of cholinergic entero-pancreatic reflex
      and CCK release. Our experimental studies have shown that exogenous melatonin, as
      well as this produced endogenously from its precursor; L-tryptophan, strongly
      stimulates pancreatic amylase secretion when given intraperitoneally, or into the
      gut lumen. Intraduodenal administration of ghrelin also increases pancreatic
      enzyme secretion. This was accompanied by significant increases of CCK plasma
      levels. Above pancreatostimulatory effects of luminal administration of melatonin
      or ghrelin were completely reversed by bilateral vagotomy, capsaicin deactivation
      of sensory nerves or pretreatment of the rats with CCK1 receptor antagonist;
      tarazepide. Our previous findings have revealed that melatonin, as well as its
      precursor; L-tryptophan, effectively protects the pancreas against the damage
      induced by caerulein overstimulation. The beneficial effects of melatonin and L
      tryptophan on the pancreas have been related to the ability of melatonin to
      scavenge the radical oxygen species (ROS), to activate antioxidative enzymes and
      to modulate the cytokine production. It has been previously shown that systemic
      application of ghrelin attenuated acute pancreatitis activating the immune
      defense mechanisms. Our recent data demonstrate that ghrelin is able to prevent
      pancreatic inflammatory damage though the activation of central nervous
      mechanisms leading to the improvement of antioxidative properties of pancreatic
      tissue. The results of experimental studies indicated that melatonin and ghrelin
      could take a part in the protection of pancreatic tissue against the damage under
      physiological conditions.

PMID- 17218762
TI  - Ghrelin in the postnatal development of the gastrointestinal tract.
AB  - Ghrelin is a 28-amino acid peptide first isolated from rat and human stomachs.
      Together with the recently discovered 23-amino acid obestatin, it is derived from
      proghrelin by posttranslational processing. Cells immunoreactive to ghrelin are
      widely distributed in the gastric mucosa in domestic and laboratory animals and
      in humans. Ghrelin plays an important role in energy homeostasis, body weight
      control, and food intake, whereas obestatin seems to induce the opposite effects.
      Ghrelin and ghrelin receptor expression have been found in developing
      gastrointestinal foetal and neonatal tissues, and substantial amounts of ghrelin
      are present in colostrum, thereby suggesting its presumable role in perinatal
      development. Ghrelin was shown to positively influence weight gain, increase GH,
      insulin and cortisol secretion. It also stimulates gastrointestinal tissue
      structure and function development in weaned animals. Surprisingly, responses in
      suckling neonates were found to be opposite to those in weanlings. Ghrelin
      retarded gastric, intestinal and pancreatic development and showed a tendency to
      reduce body weight gain. Recent studies suggest that the biphasic effect of
      ghrelin in young rats on pancreas and stomach growth seems to be related to age
      dependent changes of the release of anabolic IGF-1. In the perinatal period,
      obestatin is detected in the rat stomach, pancreas and blood plasma. The
      obestatin concentration in rats is abruptly reduced after birth, contrasting with
      an increase in the concentration of acylated ghrelin. Further progressive
      reduction in pancreas obestatin is observed until weaning.

PMID- 17218763
TI  - Inhibitors of cyclooxygenases: mechanisms, selectivity and uses.
AB  - The prostaglandins are lipid mediators, discovered in the 1930s by von Euler in
      Sweden and Goldblatt in the United Kingdom. They are made by the bifunctional
      enzyme, cyclooxygenase, which has both cyclooxygenase and peroxidase activities
      in the same molecule. Prostaglandins are involved in physiological functions such
      as protection of the stomach mucosa, aggregation of platelets and regulation of
      kidney function. They also have pathological functions such as their involvement
      in inflammation, fever and pain. Vane in 1971 elegantly showed that the
      pharmacological actions of aspirin and similar drugs were due to the inhibition
      of cyclooxygenase. Thus, aspirin-like drugs exert their anti-inflammatory,
      antipyretic and analgesic effects by inhibition of cyclooxygenase. In 1991,
      Simmons and his colleagues identified a second cyclooxygenase enzyme, designated
      cyclooxygenase-2, derived from a separate gene from cyclooxygenase-1.
      Cyclooxygenase-2 is upregulated by inflammatory mediators and forms
      prostaglandins which intensify the inflammatory response. Cyclooxygenase-1 is,
      therefore, a 'housekeeping' enzyme making prostaglandins, which are important for
      maintaining physiological functions and cyclooxygenase-2 makes prostaglandins
      which are important in inflammation. The discovery of cyclooxygenase-2 and the
      establishment of its structure led to the development of selective inhibitors of
      this enzyme, such as celecoxib and rofecoxib, with potent anti-inflammatory
      actions but with reduced gastrotoxic effects. A putative cyclooxygenase-3, has
      also been characterised and cloned. This enzyme is a product of the
      cyclooxygenase-1 gene, but retains intron 1 after transcription and translates
      into a cyclooxygenase enzyme with 34 additional amino acids. It is more sensitive
      to inhibition by paracetamol, aspirin and some other non-steroid anti
      inflammatory drugs than cyclooxygenase-1 or cyclooxygenase-2. A cyclooxygenase
      enzyme induced in cultured cells by some non-steroid anti-inflammatory drugs is
      also more sensitive to inhibition by paracetamol than cyclooxygenase-2 induced by
      bacterial lipopolysaccharide.

PMID- 17218764
TI  - Ascorbic acid attenuates aspirin-induced gastric damage: role of inducible nitric
      oxide synthase.
AB  - Aspirin (ASA) represents an important risk factor for gastric mucosal injury.
      Recently, vitamin C releasing aspirin (ASA-VitC) has been shown to reduce gastric
      toxicity of ASA in animal model of gastric injury. The aim of the present study
      was to compare the effect of ASA and ASA-VitC on the gastric mucosal damage
      before and after Helicobacter pylori (Hp) eradication in 10 young healthy Hp
      positive volunteers. All subjects underwent endoscopy at day 0 (before ASA or ASA
      VitC treatment) and at day 3 following treatment (1.6 g ASA/day or 1.6 g ASA +
      0.96 g Vit C/day). In addition, in vitro experiments were performed in which
      gastric mucosal cell line (MKN-45 cells) was incubated with ASA or ASA-VitC alone
      or in combination with H.pylori. Expression of constitutive and inducible NO
      synthase (cNOS, iNOS) was analyzed by Western blot. Moreover, COX-2 expression
      was analyzed in gastric biopsies at mRNA and protein level by RT-PCR and Western
      blot, respectively. In humans, treatment with ASA-VitC induced significantly less
      gastric mucosal lesions than plain ASA. Furthermore, in comparison to plain ASA,
      ASA-VitC caused stronger inhibition of cNOS and increase in iNOS expression in
      the gastric mucosa. In vitro studies demonstrated a significant increase in iNOS
      expression in MKN-45 cells incubated with Hp. This effect was aggravated by the
      addition of ASA, but not ASA-VitC, to MKN-45 cells incubated with H.pylori. Both
      ASA and ASA-VitC stimulated the COX-2 expression in the gastric mucosa. We
      conclude that ASA-VitC in comparison with ASA induces less gastric mucosal damage
      and this protective effect may be due to its inhibitory effect on iNOS
      expression.

PMID- 17218765
TI  - Cannabinoids in acute gastric damage and pancreatitis.
AB  - Recent studies have shown that stimulation of cannabinoid 1 (CB1) receptor
      reduces the area of ischemic myocardial necrosis and affects activity of the
      digestive tract. The aim of the present study was to check whether the
      administration of CB1 receptor agonist or antagonist affects the stress-induced
      gastric ulceration and development of edematous pancreatitis. METHODS:
      Experiments were performed on rats. Gastric lesions were induced by water
      immersion and restrain stress (WRS). Acute pancreatitis was induced by cerulein.
      Prior to WRS or before and during cerulein administration, a natural endogenous
      ligand for CB1 receptor, anandamide was administered intraperitoneally at the
      dose of 0.8, 1.5 or 3.0 micromol/kg. A synthetic CB1 receptor antagonist, AM 251
      (ALEXIS(R) Biochemicals) was administrated at the dose of 4 micromol/kg i.p.
      alone or in combination with anandamide at the dose of 1.5 micromol/kg. RESULTS:
      Administration of anandamide reduced gastric lesions and this effect was
      associated with am increase in gastric mucosal blood flow and mucosal DNA
      synthesis; whereas serum level of pro-inflammatory interleukin-1 beta was
      reduced. Treatment with AM 251 aggravated gastric damage and reversed protective
      effect of anandamide administration. Opposite effect was observed in the
      pancreas. Administration of anandamide increased dose-dependently the severity of
      pancreatitis. In histological examination, we observed an increase in pancreatic
      edema and inflammatory infiltration. Also, treatment with anandamide augmented
      the pancreatitis-induced increase in serum level of lipase, amylase, poly-C
      ribonuclease, and pro-inflammatory interleukin-1 beta; whereas pancreatic DNA
      synthesis was reduced. Treatment with AM 251 reduced histological and biochemical
      signs of pancreatic damage and reversed deleterious effect of anandamide in
      cerulein-induced acute pancreatitis. CONCLUSIONS: Activation of CB1 receptors
      evokes opposite effects in the stomach and pancreas: in the stomach, exhibits
      protective effect against stress-induced gastric mucosal lesions; whereas in the
      pancreas, increases the severity of cerulein-induced pancreatitis.

PMID- 17218767
TI  - Dramatic reduction of microemboli after heparin infusion in progressing stroke
      due to aortic arch atheroma.

PMID- 17218766
TI  - Influence of Viburnum opulus proanthocyanidins on stress-induced gastrointestinal
      mucosal damage.
AB  - Recent studies demonstrated that the proanthocyanidins (PA), the polymers of
      flavan-3-ols, naturally occurring plant metabolites widely available in fruits,
      vegetables, nuts, seeds, flowers and bark, have anti-inflammatory,
      anticarcinogenic, anti-allergic, antioxidant and vasodilatory actions. We
      hypothesized that Viburnum opulus PA (VOPA, Caprifoliaceae), due to activation of
      multifactorial gastrointestinal mucosal defense mechanisms, exert
      gastroduodenoprotective effects. The aim of the study was: 1) to investigate VOPA
      effects on gastroduodenal mucosal integrity and pattern of carbohydrate binding
      proteins and nitric oxide (NO) content in intact mucosa and that exposed to non
      topical ulcerogens (stress) in rats without and with capsaicin (125 mg/kg, sc)
      denervation; and 2), to assess the role of activity of antioxidizing enzymes
      superoxide dismutase (SOD), catalase (CAT), gluthatione peroxidase (GPx) in VOPA
      induced gastroduodenoprotection against water immersion and restraint stress
      (WRS) in rats. VOPA was administered orally in dose of 25, 50 or 75 mg/kg body
      weight. Gastroduodenal mucosal damage detected by routine light microscopic
      investigation and lectin histochemistry set, purified from plant and animal
      sources of Carpatian region. NO content, pro-and antioxidant system were
      determined by routine laboratory methods. Pretreatment with VOPA afforded
      gastroduodenoprotection and was accompanied by an increase in NO expression, both
      changes being reversed by sensory denervation, as well as by the rise of SOD, CAT
      activity and fall in MDA content. Our study shows that VOPA exerts a potent
      gastroduodenoprotective activity via an increase in endogenous NO generation,
      suppression of lipid peroxidation and mobilization of antioxidant activity and
      changes in glycoconjugate content of the gastroduodenal mucosa of rat.

PMID- 17218769
TI  - Sweet's syndrome associated with acute-onset encephalitis.

PMID- 17218768
TI  - Paraneoplastic cerebellar ataxia due to burnt-out testicular germ cell tumour?

PMID- 17218770
TI  - Osler and the Churg-Strauss syndrome.
AB  - This paper records a patient of Osler's, who showed many features compatible with
      the Churg-Strauss syndrome of allergic granulomatous angiitis to be described 50
      years later.

PMID- 17218771
TI  - Brain-to-brain paradoxical embolism through patent foramen ovale after cerebral
      vein thrombosis.

PMID- 17218772
TI  - Thalamus.

PMID- 17218773
TI  - Palsy.

PMID- 17218774
TI  - Bin1 attenuation in breast cancer is correlated to nodal metastasis and reduced
      survival.
AB  - Clinical outcomes in breast cancer are likely influenced by modifier genes that
      affect tumor dormancy versus progression. The Bin1 gene encodes a nucleocytosolic
      adapter protein that suppresses neoplastic cell transformation and that is often
      attenuated in human breast carcinoma. Recent mouse genetic studies indicate that
      Bin1 loss cooperates with ras activation to drive progression of mammary
      carcinoma, establishing Bin1 as a negative modifier of tumor progression in
      breast cancer. In this study, we investigated whether immunohistochemical losses
      of nuclear Bin1 proteins in cases of human breast cancer were correlated to
      progression status. In American and Japanese groups of low or middle grade breast
      cancers, losses were associated with reduced survival and increased nodal
      metastasis, respectively. Taken together with recent findings from mouse genetic
      studies, these findings encourage further evaluation of the potential utility of
      Bin1 as a clinical prognostic marker in breast cancer.

PMID- 17218775
TI  - Oridonin induced apoptosis through Akt and MAPKs signaling pathways in human
      osteosarcoma cells.
AB  - Previous studies have shown that oridonin, a diterpenoid isolated from Rabdosia
      rubescens, was able to inhibit proliferation and induce apoptosis in several cell
      types. But the mechanisms remain poorly understood. In this study, we
      investigated the apoptosis-inducing effect and mechanisms of action of oridonin
      in human osteosarcoma cells. Our results demonstrated that oridonin induced
      concentration- and time-dependent suppression of proliferation and activation of
      apoptosis in U2OS, MG63 and SaOS-2 osteosarcoma cell lines. Oridonin induced the
      release of cytochrome c accompanied by activation of caspase-9, caspase-3 and
      cleavage of poly(ADP-ribose) polymerase (PARP). These events were all inhibited
      by z-VAD-fmk, a universal inhibitor of caspases. Oridonin treatment
      dephosphorylated constitutively active AKT, FOXO transcription factor, and
      glycogen synthase kinase 3 (GSK3). In addition, oridonin decreased the
      phosphorylation of ERK and increased the phosphorylation of p38 MAPK and JNK.
      Furthermore, oridonin treatment down-regulated the expression of the inhibitor of
      apoptosis protein(IAP) in osteosarcoma cells. All together, our results suggested
      that oridonin is able to inactivate Akt and ERK and activate p38 MAPK and JNK
      signalling pathways in osteosarcoma cells causing the suppression of
      proliferation and induction of mitochondria- and caspase-dependent apoptosis.

PMID- 17218776
TI  - Combining an mTOR antagonist and receptor tyrosine kinase inhibitors for the
      treatment of prostate cancer.
AB  - Inhibition of the mammalian target of rapamycin (mTOR) signaling pathway is a
      potentially useful therapeutic strategy in the treatment of advanced prostate
      cancer. However mTOR antagonists used as single agents are not likely to result
      in dramatic clinical responses, so that it is useful to identify prospective
      agents that might be useful in combination. We treated CWR22Rv1 and LNCaP
      prostate cancer cells with an mTOR inhibitor, rapamycin, alone, or in combination
      with either of two receptor protein kinase (RTK) inhibitors. We assessed the
      effects of these treatments on cell survival and activation of down-stream mTOR
      target proteins. Treatment with either PD16839, an EGFr antagonist, or imatinib
      mesylate (Gleevec), a PDGFr, c-kit and bcr/abl antagonist, enhanced the anti
      proliferative effects of rapamycin. We therefore assessed the effects of
      treatment with the RTK antagonist alone and in combination with rapamycin on mTOR
      targeted proteins. RTK antagonists alone had no effect or paradoxically increased
      phosphorylation of the mTOR targeted proteins, p70 S6 kinase and ribosomal S6. In
      contrast, when these cells were treated with either RTK antagonist in the
      presence of rapamycin, there was a dramatic decrease in phosphorylation of these
      two mTOR-targeted proteins. These effects were not mediated through phospho-AKT.
      Since two separate RTK antagonists had additive antiproliferative effects in
      combination with an mTOR antagonist and were associated with a dramatic decrease
      in mTOR targeted proteins in cells with or without PTEN expression, the strategy
      deserves further evaluation for the treatment of prostate cancer.

PMID- 17218777
TI  - Active immunotherapy with 1E10 anti-idiotype vaccine in patients with small cell
      lung cancer: report of a phase I trial.
AB  - 1E10 is an anti-idiotype murine monoclonal antibody (Ab2 MAb) specific to an Ab1
      MAb which reacts with NeuGc-containing gangliosides, sulfatides and with antigens
      expressed in some human tumors. Preparations containing this Ab2 were capable to
      induce a strong anti-metastatic effect in tumor-bearing mice. We conducted a
      Phase I clinical trial to evaluate the toxicity and humoral immune response
      elicited by 1E10 vaccine in patients with small cell lung cancer (SCLC). Eligible
      patients were those who after received chemotherapy and/or radiotherapy had
      partial or complete response to treatment. Patients received four biweekly
      injections with 2 mg of aluminum hydroxide-precipitated 1E10 MAb, then other six
      doses at 28-day intervals, and later the patients who maintained a good
      performance status were reimmunized. Six patients with limited-stage disease and
      three with extensive-stage disease were enrolled in the study. Most of the
      patients who received at least four doses of 1E10 vaccine developed strong
      specific antibody responses against 1E10 MAb and NeuGc-GM3 ganglioside.
      Antibodies able to react with lung carcinoma tissue sections were detected in
      sera from vaccinated patients. A prolonged survival was observed in several
      patients treated with the anti-idiotype vaccine. No evidence of serious adverse
      effects was found.

PMID- 17218778
TI  - Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in
      human osteosarcoma cells.
AB  - We have recently shown that thymoquinone (TQ) is an antineoplastic drug that
      induces p53-dependent apoptosis in human colon cancer cells. This study evaluated
      the antiproliferative and pro-apoptotic effects of TQ in two human osteosarcoma
      cell lines with different p53 mutation status. TQ decreased cell survival dose
      dependently and, more significantly, in p53-null MG63 cells (IC(50) = 17 muM)
      than in p53-mutant MNNG/HOS cells (IC(50) = 38 muM). Cell viability was reduced
      more selectively in MG63 tumor cells than in normal human osteoblasts. Flow
      cytometric analysis showed that TQ induced a much greater increase in the PreG(1)
      (apoptotic) cell population, but no cell cycle arrest in MG63. G(2)/M arrest in
      MNNG/HOS cells was associated with p21(WAF1) upregulation. Using three DNA damage
      assays, TQ was confirmed to result in a significantly greater extent of apoptosis
      in p53 null MG63 cells. Although the Bax/Bcl-2 ratios were not differentially
      modulated in both cell lines, the mitochondrial pathway appeared to be involved
      in TQ-induced apoptosis in MG63 by showing the cleavage of caspases-9 and -3.
      Oxidative stress and mitochondrial O(2)(*-) generation in isolated rat
      mitochondria were enhanced by TQ as measured by the dose-dependent reduction in
      aconitase enzyme activity and Amplex Red oxidation respectively. TQ-induced
      oxidative damage, reflected by an increase in gamma-H2AX foci and increased
      protein expression levels of gamma-H2AX and the DNA repair enzyme, NBS1, was more
      pronounced in MNNG/HOS than in MG63. We suggest that the resistance of MNNG/HOS
      cells to drug-induced apoptosis is caused by the up-regulation of p21(WAF1) by
      the mutant p53 (transcriptional activity was shown by p53 siRNA treatment) which
      induces cell cycle arrest and allows to repair DNA damage. Collectively, these
      findings show that TQ induces p53-independent apoptosis in human osteosarcoma
      cells. As the loss of p53 function is frequently observed in osteosarcoma
      patients, our data suggest the potential clinical usefulness of TQ for the
      treatment of these malignancies.

PMID- 17218779
TI  - Forced expression of RDH10 gene retards growth of HepG2 cells.
AB  - The constitutive over-expression of the retinol dehydrogenase 10 (RDH10) gene,
      involved in retinoic acid (RA) biosynthesis, produced in HepG2 cells a
      significant antiproliferative response, but not signs of apoptosis. An indirect
      assay based on the Chloramphenicol AcetylTransferase (CAT) reporter gene driven
      by a retinoic acid responsive element (RARE) suggests in genetically modified
      HepG2 cells an increase of the endogenous RA concentration. Furthermore, the
      growth arrest of HepG2 cells over-expressing the RDH10 gene was associated with
      the upregulation and downregulation of, respectively, RARbeta/p21(Cip1) and
      CycE/CdK2 mRNAs. These results indicated that forced expression of RDH10 produces
      antiproliferative effects highly comparable to those achieved by retinoids
      treatment and thus the development of a gene therapy, finalized at the
      restoration of the enzymatic and receptorial machinery of the RA pathway, could
      be a possible curative strategy for hepatocellular carcinoma (HCC).

PMID- 17218781
TI  - Dose-dependent reduction of dietary protein-induced colonocyte DNA damage by
      resistant starch in rats correlates more highly with caecal butyrate than with
      other short chain fatty acids.
AB  - Previous studies have shown increased levels of colonocyte DNA damage (as
      measured by the comet assay) and thinning of the colonic mucus layer in rats fed
      higher dietary protein as casein or red meat with highly digestible starch.
      Feeding resistant starch (RS) as high amylose maize starch (HAMS) opposed these
      changes. However, the dietary level of HAMS was relatively high (48% by weight)
      so this study was conducted to establish whether HAMS had the same effects at
      lower dietary levels. Adult male rats were fed a diet containing 25% casein with
      0%, 10%, 20%, 30% or 40% HAMS for 4 wk. DNA single strand breaks and 8
      hydroxyguanosine levels were measured in isolated colonocytes by the comet assay.
      As expected, comet tail moment was greatest and the mucus barrier thinnest in
      rats fed 0% HAMS. DNA damage was reduced and the mucus barrier thickened in a
      logarithmic dose-dependent manner by HAMS. There was no significant difference in
      8-hydroxyguanosine between dietary groups. Caecal and fecal short chain fatty
      acid (SCFA) pools rose with the increased level of dietary HAMS. DNA damage of
      colonocytes correlated negatively with caecal SCFA but the strongest correlation
      was with caecal butyrate, which is consistent with the proposed role of this SCFA
      in promoting a normal cell phenotype. These data show that HAMS prevents protein
      induced colonic DNA damage in a dose-dependent manner. Inclusion of 10% HAMS was
      found to be sufficient to oppose colonocyte DNA damage, and to increase caecal
      and fecal SCFA pools.

PMID- 17218780
TI  - Selectively oncolytic mutant of HSV-1 lyses HeLa cells mediated by Ras/RTN3.
AB  - The selectively oncolytic mtHSV, a HSV icp34.5 mutant with lacz gene insertion,
      was proved that it was targeted for treating tumors but not other organs,
      however, its oncolytic mechanism is under confirmation. The results showed that
      HeLa cells could be lysed efficiently by mtHSV in vitro. In the flow cytometry
      and Western blot experiment, Ras protein was obviously downregulated on plasma
      membrane (PM) while the whole Ras protein didn't change along with upregulation
      of reticulon 3(RTN3) protein at 48 h post infection of mtHSV in HeLa cells.
      Expression of Ras protein on PM and whole Ras protein in HeLa cells was
      downregulated by siFTa (inhibitor of a subunits of human farnesyltransferase with
      siRNA) and siRTN3(inhibitor of RTN3 with siRNA) respectively, and HeLa cells
      could be killed effectively by siFTa and siRTN3 at 48 h post transfection. So
      siFTa and siRTN3 effectively suppressed mtHSV infection of HeLa cells. Further,
      experiments were made to study the relationship between Ras and RTN3 using
      confocal colocalization and coimmunoprecipitation. The results exhibited that Ras
      could interact with RTN3 at endoplasmic reticulum. The data put forward that
      Ras/RTN3 is an important access to HeLa cells for mtHSV. The molecular
      interaction between Ras and RTN3 may further improve the understanding of the
      function of Ras and RTN3 in mtHSV infection. The results provide further
      theoretical evidence that mtHSV may be used as an oncolytic agent for cancer
      therapy.

PMID- 17218782
TI  - Valproic acid induces apoptosis, p16INK4A upregulation and sensitization to
      chemotherapy in human melanoma cells.
AB  - It is known that melanoma develops as a consequence of multifactorial
      alterations. To date several studies indicate the effective implication of p16 as
      a tumor suppressor gene with a major role in either the development or
      progression of human melanoma. Deregulation of melanoma cell growth has been
      widely associated with mutations in the p16-cyclin D/cdk4-pRb pathway. Recently
      anticancer therapies are focused on restoration of p16 CDK inhibitory function
      and other proteins unregulated in melanoma cell cycle pathway (e.g., c-myc, p27).
      A combined strategy for restoration of normal homeostasis in the melanoma skin
      with targeted delivery of apoptosis-inducing agents does not seems to be far
      obtained. New class of antitumoral agents are emerging: histone deacetylase
      (HDAC) inhibitors have attracted much interest because of their ability to arrest
      cell growth, induce cell differentiation, and in some cases, induce apoptosis of
      cancer cells. Recently, attention has been focused on the ability of HDAC
      inhibitors to induce perturbation in cell cycle regulatory protein (e.g.,
      p21(CIP1)) and down-regulation of survival signalling pathway. In the present
      study, we have examined the effect of valproic acid (VPA) on M14 human melanoma
      cell line. Here we observed that VPA induces cell cycle arrest and apoptosis
      sensitising melanoma cells to cis-platin and etoposide treatment. IC(50) dose
      (2.99 mM) of VPA was able to induce G(1) arrest (up to 75%) in association with
      upregulation of p16, p21 and cyclin-D1 related to Rb ipo-phosphorilation. In
      addition VPA activated apoptosis (50%) in M14 cells, when given alone or in
      combination with antitumoral agents. The ability of valproic acid to
      reestablished the G(1) pathway in melanoma cells suggests a potential application
      of VPA in melanoma therapeutic protocols.

PMID- 17218784
TI  - Effects of etoposide and cyclophosphamide acute chemotherapy on growth plate and
      metaphyseal bone in rats.
AB  - Pediatric cancer chemotherapy is known to cause bone growth arrest and
      osteoporotic changes, and yet the underlying mechanisms remain largely unknown.
      This project investigated effects of acute chemotherapy with topoisomerase
      inhibitor etoposide (Eto, 80 mg/kg), alkylating agent cyclophosphamide (Cyc, 240
      mg/kg) or their combination (Cyc 120 mg/kg + Eto 50 mg/kg) on structural and
      cellular changes in the growth plate cartilage and metaphyseal bone, two
      important regions responsible for bone growth and bone mass accumulation. On day
      3 after a single injection with either of the three treatments, although the
      total growth plate thickness was not significantly altered, the cellularity and
      height of the proliferative zone were significantly reduced. It was shown that
      while Eto suppressed chondrocyte proliferation, Cyc induced apoptosis in the
      growth plate proliferative zone. In the metaphysis, although osteoblastic cell
      surface was decreased in all three treated groups, the trabecular bone bone
      volume (BV/TV%) was not significantly altered on day 3. On the other hand, the
      acute chemotherapy reduced heights of both primary and secondary spongiosa
      trabecular bone. Therefore, Eto and/ or Cyc chemotherapy altered survival or
      proliferation of growth plate chondrocytes and metaphyseal osteoblastic cells and
      reduced heights of metaphyseal spongiosa trabecular bone, which may contribute to
      chemotherapy side effects of these two drugs on bone lengthening and bone mass
      accumulation.

PMID- 17218783
TI  - Curcumin induces G2/M arrest and apoptosis in cisplatin-resistant human ovarian
      cancer cells by modulating Akt and p38 MAPK.
AB  - Curcumin, a major active component of turmeric, is known to induce apoptosis in
      several types of cancer cells, but little is known about its activity in
      chemoresistant cells. Hence, the aim of the present study was to investigate the
      anticancer properties of curcumin in cisplatin-resistant human ovarian cancer
      cells in vitro. The results indicated that curcumin inhibited the proliferation
      of both cisplatin-resistant (CR) and sensitive (CS) human ovarian cancer cells
      almost equally. Enhanced superoxide generation was observed in both CR and CS
      cells treated with curcumin. Curcumin induced G(2)/M phase cell-cycle arrest in
      CR cells by enhancing the p53 phosphorylation and apoptosis through the
      activation of caspase-3 followed by PARP degradation. Curcumin also inhibited the
      phosphorylation of Akt while the phosphorylation of p38 MAPK was enhanced. In
      summary, our results showed that curcumin inhibits the proliferation of cisplatin
      resistant ovarian cancer cells through the induction of superoxide generation,
      G(2)/M arrest, and apoptosis.

PMID- 17218785
TI  - Zyflamend-mediated inhibition of human prostate cancer PC3 cell proliferation:
      effects on 12-LOX and Rb protein phosphorylation.
AB  - The multiherb anti-inflammatory product Zyflamend was investigated for its
      antiproliferative effects on PC3 human prostate cancer cells and eicosanoid
      metabolism in this prostate cancer cell line. Zyflamend produced a concentration
      dependent inhibition of cloned COX-1, COX-2, and 5-LOX enzyme activities, with
      inhibition of 5-HETE production being greater than that of PGE(2) formation.
      Applied to intact PC3 cells, Zyflamend was found to be most potent against 12
      LOX, followed by 5-LOX and then COX activities. The concentration-dependent
      inhibition of PC3 cell proliferation was associated with a selective G(2)/M
      arrest of the cell cycle and induction of apoptosis, as evidenced by flow
      cytometric staining of PC3 cells with annexin V. Zyflamend also produced a
      concentration-dependent down-regulation of 5-LOX and 12-LOX expression.
      Determination of cell signal transduction proteins demonstrated that Zyflamend
      produced an increase in p21 phosphorylation but down-regulated phosphorylation of
      retinoblastoma (Rb) protein. The decrease in pRb protein was shown to be due to
      12-LOX inhibition and a decline in 12-HETE levels in the cells. Replenishing 12
      HETE in Zyflamend-treated cells overcame the ability of this multiple herb
      product to inhibit cell proliferation, and concordantly, 12-HETE blocked
      Zyflamend's ability to down-regulate phosphorylation of Rb protein. We conclude
      that the effective control of human prostate cancer cell proliferation with
      Zyflamend is multi-mechanistic but, in part, involves regulation of aberrant
      tumor cell eicosanoid metabolism, especially on 5- and 12-LOX, as well as
      restoration of Rb tumor suppressor protein function through regulation of its
      phosphorylation status.

PMID- 17218786
TI  - Novel therapeutic target: the PERKs of inhibiting the integrated stress response.
AB  - Oxygen supports the life of all aerobic organisms and virtually every cell type
      is capable of sensing decreased tissue oxygenation or hypoxia. Hypoxic
      microenvironments are known to exist within developing solid tumors as a result
      of insufficient vascular delivery of oxygen, which can limit the efficient growth
      and spread of the malignancy. On the other hand, clinical and experimental
      evidence has demonstrated that reduction in tumor blood flow can diminish the
      efficacy of standard anticancer therapeutics including radiotherapy and
      chemotherapy. Indeed, low oxygenation can accelerate malignant progression and
      metastasis resulting in poorer prognosis irrespective of the chosen treatment
      regiment. We and others have shown that tumor cells cultured under hypoxic
      conditions and cells in hypoxic areas of tumors activate a translational control
      program known as the integrated stress response (ISR). One of the key master
      switches in the ISR is the dynamically regulated protein kinase known as PERK.
      Tumors that lack PERK activity are small and compromised in their ability to
      translate mRNAs involved in angiogenesis and tumor survival. PERK can be
      activated by a number of distinct endoplasmic reticulum (ER) stress as well as
      hypoxia and promotes a tumor microenvironment that favors the formation of
      functional microvessels and ultimately tumor growth. We hypothesize that ER
      stress induced by sub-lethal doses of anti-cancer therapeutics could actually
      facilitate tumor progression by activation of the ISR. We propose that inhibitors
      of PERK may synergize with a variety of cancer therapeutics that directly or
      indirectly induce the ISR.

PMID- 17218787
TI  - Ubiquitin transfer from the E2 perspective: why is UbcH5 so promiscuous?
AB  - Protein ubiquitination is a regulatory process that influences nearly every
      aspect of eukaryotic cell biology. Pathways that range from cell-cycle
      progression and differentiation to DNA repair to vesicle budding all rely on
      regulated modification of target proteins by ubiquitin. Target proteins can be
      tagged by a single molecule of ubiquitin or modified by ubiquitin polymers that
      can vary in length and linkage specificity, and these variations influence how
      ubiquitination signals are interpreted. Surprisingly, little is understood
      regarding mechanisms of protein ubiquitination and how poly-ubiquitin chains are
      synthesized. Simple models to explain ubiquitin transfer have dominated the
      literature, but recent work suggests basic assumptions as to how proteins
      assemble to facilitate protein ubiquitination and poly-ubiquitin chain synthesis
      should be reexamined. This is particularly necessary for understanding the roles
      played by E2 ubiquitin-conjugating enzymes, a central protein component in all
      ubiquitin transfer reactions. In particular, UbcH5, a canonical E2 protein that
      is active in a broad number of in vitro ubiquitin transfer reactions, is capable
      of binding ubiquitin noncovalently on a surface distinct from its active site.
      This unique property allows activated UbcH5 approximately Ub complexes to self
      assemble and has a profound influence on poly-ubiquitin chain synthesis.

PMID- 17218789
TI  - Beta-catenin signaling: linking renal cell carcinoma and polycystic kidney
      disease.
AB  - Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial
      and most sporadic renal cell carcinoma (RCC), resulting in the aberrant
      expression of genes that control cell proliferation, invasion and angiogenesis.
      The molecular mechanisms by which VHL loss leads to tumorigenesis are not yet
      fully defined. The VHL gene product, pVHL, is part of an E3 ubiquitin ligase
      complex that targets hypoxia inducible factors for polyubiquitination and
      proteosomal degradation, implicating hypoxia response genes in RCC oncogenesis.
      VHL loss also allows robust RCC cell invasiveness and morphogenesis in response
      to hepatocyte growth factor (HGF), an important regulator of kidney development
      and renal homeostasis. Recent elucidation of the mechanism by which pVHL
      represses developmental HGF responses in adult kidney has identified another
      oncogenically relevant E3 ligase target: beta-catenin. This discovery also
      further unifies recent insights into the molecular pathogenesis of polycystic
      kidney disease, where the identification of disease genes has revealed the
      integration of signaling pathways associated with primary cilia function and the
      regulation of cell growth and differentiation.

PMID- 17218788
TI  - TGF-beta activated kinase-1: new insights into the diverse roles of TAK1 in
      development and immunity.
AB  - A number of recent publications have examined the role of TAK1 in model systems
      ranging from fly to mouse. Rather than fit into a clearly defined linear
      molecular pathway, TAK1 seems to act in a signaling nexus that responds to a
      variety of upstream signals, including inflammatory molecules and developmental
      cues. TAK1 then influences a number of downstream processes ranging from innate
      immune responses to patterning and differentiation via JNK, NFkappaB and TCFbeta
      catenin signaling. These differences in function are not simply a matter of cell
      type. For example, NFkappaB signaling in a particular cell may or may not require
      TAK1 depending on the nature of the activating signal. Interestingly, the multi
      task functionality of TAK1 is conserved between vertebrate and invertebrate
      species. Studies of TAK1 in multiple experimental systems is likely to reveal
      more roles for this kinase and also elucidate mechanisms by which other signaling
      molecules fulfill diverse signaling roles. Here we provide an overview of the
      data concerning TAK1 from its discovery to more recent findings and provide a
      synthesis of the conclusions that have arisen from the multiple model systems and
      experimental approaches.

PMID- 17218790
TI  - Oncogenic shock: turning an activated kinase against the tumor cell.
AB  - Accumulating evidence indicates that mutationally activated kinases are
      especially good targets for anti-cancer drugs. It has been suggested that this
      reflects a state of "oncogene addiction" of tumor cells. We recently reported
      experimental studies that may provide a molecular mechanism to explain such
      apparent dependency. We find that oncogenic kinases produce both pro-survival and
      pro-apoptotic signals that decay at different rates upon oncogene inactivation.
      Pro-survival signals are rapidly attenuated, whereas pro-apoptotic signals are
      relatively longer-lived. This differential signal decay creates a temporal window
      during which pro-apoptotic outputs from the oncogenic kinase predominate to
      actively promote tumor cell death upon kinase inhibition. We refer to this
      mechanism as "oncogenic shock", and suggest that it has significant implications
      for the optimal therapeutic use of targeted kinase inhibitors.

PMID- 17218791
TI  - Phosphatase and feedback regulation of Raf-1 signaling.
AB  - The Raf-1 kinase is an effector of Ras GTPases that lies at the apex of the three
      tier Raf/MEK/ERK pathway. Raf-1 activation is a complex process that entails two
      major events--relief of autoinhibition imposed by the regulatory domain and
      kinase domain activation. Recent studies indicate that the transition of Raf-1
      from an active to an inactive state bears similar complexity to the activation
      process. Both these events require dynamic changes in Raf-1 phosphorylation.
      Here, we discuss the critical role of phosphatases and feedback phosphorylation
      during activation and inactivation of Raf-1 signaling.

PMID- 17218792
TI  - Effects of intrathecal injection of T-type calcium channel blockers in the rat
      formalin test.
AB  - T-type Ca2+ channels have been implicated in the induction of long-term
      potentiation, a synaptic plasticity involved in the central sensitization that
      contributes to the generation of inflammatory pain, in spinal sensory neurons. In
      this study, we examined the effects of intrathecal T-type Ca2+ channel blockers,
      mibefradil, ethosuximide and NiCl2, in the rat formalin test, an inflammatory
      pain model. Biphasic characteristic nociceptive behaviors were induced by
      intraplantar injection of formalin (5% formaldehyde, 50 microl) in Sprague-Dawley
      rats and monitored at 0-9 min (phase 1) and 10-60 min (phase 2) after formalin
      injection. Intrathecal pretreatment with mibefradil (50-500 microg) and NiCl2 (1
      10 microg) dose-dependently decreased the flinch numbers and biting and licking
      time in both phases. The ID50s of mibefradil in inhibiting the phases 1 and 2
      flinch responses were 74.3+/-4.6 and 100.9+/-8.7 microg, respectively, and those
      of NiCl2 were 2.7+/-1.1 and 3.3+/-0.1 microg, respectively. Ethosuximide, at the
      doses up to 1200 microg, however, did not affect the nociceptive responses in
      both phases. It is suggested that spinal T-type Ca2+ channels may play a role in
      formalin-induced inflammatory pain. The ineffectiveness of ethosuximide is
      discussed.

PMID- 17218793
TI  - Olanzapine and JL13 induce cross-tolerance to the clozapine discriminative
      stimulus in rats.
AB  - We have previously shown that chronic treatment with clozapine induces tolerance
      to the clozapine discriminative stimulus in rats. The studies reported here
      extended this work to assess whether chronic treatment with the clozapine-like
      antipsychotics olanzapine and 5-(4-methylpiperazin-1-yl)-8-chloro-pyrido[2,3
      b][1,5] benzoxazepine fumarate (JL13) induced cross-tolerance to clozapine. Two
      groups of rats were trained to discriminate clozapine (5 mg/kg, intraperitoneal).
      Training was suspended and the rats were treated with either olanzapine or JL13
      at high doses (5 and 20 mg/kg, respectively). These doses were administered twice
      daily. The clozapine generalization curve was computed three times - before
      chronic drug treatment, after 10 days of chronic treatment, and after 16 drug
      free days. Both olanzapine and JL13 induced cross-tolerance to the clozapine
      stimulus, shown by significant 3.4 and 3.9 fold parallel shifts to the right in
      the clozapine generalization curves. Cross-tolerance was lost spontaneously
      during the drug-free days after treatment as clozapine sensitivity returned to
      baseline. We interpret these findings as indicative of the development of
      pharmacodynamic cross-tolerance to clozapine. Possible neuroadaptive mechanisms
      involved in such cross-tolerance are discussed. The paradigm outlined here allows
      refinement of antipsychotic drug discrimination assays to identify common chronic
      effects of such drugs.

PMID- 17218794
TI  - Polyinosinic:polycytidylic acid induces memory processing deficits in the day-old
      chick.
AB  - Anecdotal and experimental evidence has demonstrated that humans and animals
      exhibit physiological and cognitive alterations in response to sickness and
      injury. It is now clear that these changes are due to the actions of
      proinflammatory cytokines. The current study examined the effects of peripheral
      administration of polyinosinic:polycytidylic acid, a synthetic double-stranded
      viral RNA, on the memory processes of day-old chicks trained on a single trial
      passive avoidance task. Polyinosinic:polycytidylic acid impaired performance on
      the passive avoidance task in a dose-dependent manner. Maximal deficits were
      observed when 5 g/kg polyinosinic:polycytidylic acid was administered 120 min
      before training. Tests for retention revealed that interference in memory
      consolidation appeared between 30 and 40 min after training. These results
      indicate an inhibitory effect of polyinosinic:polycytidylic acid on the processes
      of memory formation at the transition from intermediate-term memory phase (A) to
      intermediate-term memory phase (B) of the Gibbs and Ng model of memory formation.
      The study also investigated the pyrogenic actions of polyinosinic:polycytidylic
      acid, and examined the effect of pretreatment with ketoprofen, a cyclooxygenase
      inhibitor. Significant rises in body temperature were observed 30 min after
      injection of polyinosinic:polycytidylic acid. Inhibition of cyclooxygenase by
      ketoprofen ameliorated the polyinosinic:polycytidylic acid-induced deficits in
      retention and attenuated the increase in body temperature. These results
      demonstrate that polyinosinic:polycytidylic acid induces memory processing
      deficits and is pyrogenic in the day-old chick and that these effects are
      cyclooxygenase-dependent.

PMID- 17218795
TI  - Roles of hippocampal nitric oxide and calcium/calmodulin-dependent protein kinase
      II in inhibitory avoidance learning in rats.
AB  - This study investigated the interactive roles of nitric oxide and
      calcium/calmodulin-dependent protein kinase II in inhibitory avoidance learning.
      In Experiment I, rats were trained on a one-trial step-through inhibitory
      avoidance learning task, whereas the controls were trained in a noncontingent
      stimulus-pairing condition. The experimental rats showed significantly higher
      retention scores than the control rats. Correspondingly, the rats in the
      experimental group showed significantly higher Ca2+-independent activity of the
      hippocampal calcium/calmodulin-dependent protein kinase II and a significant
      increase in the endogenous phosphorylation of neuronal nitric oxide synthase. The
      intrahippocampal infusion of 7-nitro-indazole, 2-[N-(2-hidroxyethyl)-N-(4-methoxy
      benzenesulfonyl)]-amino-N-(4-chlorocinnamyl)-N-methylbenzylamine, or 2-amino-5
      phosphonopentanoic acid disrupted inhibitory avoidance learning. Sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis analysis showed that these drugs
      significantly depressed phosphorylation of hippocampal nitric oxide synthase. The
      Ca2+-independent activity of hippocampal calcium/calmodulin-dependent protein
      kinase II was significantly lower in the 2-[N-(2-hidroxyethyl)-N-(4-methoxy
      benzenesulfonyl)]-amino-N-(4-chlorocinnamyl)-N-methylbenzylamine or the 2-amino-5
      phosphonopentanoic acid-infused group compared with the controls. Although these
      depressed activities were not reversed by the infusion of a nitric oxide donor
      (sodium nitroprusside), this did significantly improve the rats' inhibitory
      avoidance deficit. These results, taken together, indicate that the nitric oxide
      synthase activation is essential for inhibitory avoidance learning, which may be
      triggered via the calcium/calmodulin-dependent protein kinase II activation in
      the hippocampus.

PMID- 17218796
TI  - Methylphenidate and its ethanol transesterification metabolite ethylphenidate:
      brain disposition, monoamine transporters and motor activity.
AB  - Ethylphenidate is formed by metabolic transesterification of methylphenidate and
      ethanol. Study objectives were to (a) establish that ethylphenidate is formed in
      C57BL/6 (B6) mice; (b) compare the stimulatory effects of ethylphenidate and
      methylphenidate enantiomers; (c) determine methylphenidate and ethylphenidate
      plasma and brain distribution and (d) establish in-vitro effects of
      methylphenidate and ethylphenidate on monoamine transporter systems. Experimental
      results were that: (a) coadministration of ethanol with the separate
      methylphenidate isomers enantioselectively produced l-ethylphenidate; (b) d and
      dl-forms of methylphenidate and ethylphenidate produced dose-responsive increases
      in motor activity with stimulation being less for ethylphenidate; (c) plasma and
      whole-brain concentrations were greater for ethylphenidate than methylphenidate
      and (d) d and DL-methylphenidate and ethylphenidate exhibited comparably potent
      low inhibition of the dopamine transporter, whereas ethylphenidate was a less
      potent norepinephrine transporter inhibitor. These experiments establish the
      feasibility of the B6 mouse model for examining the interactive effects of
      ethanol and methylphenidate. As reported for humans, concurrent exposure of B6
      mice to methylphenidate and ethanol more readily formed l-ethylphenidate than d
      ethylphenidate, and the l-isomers of both methylphenidate and ethylphenidate were
      biologically inactive. The observed reduced stimulatory effect of d
      ethylphenidate relative to d-methylphenidate appears not to be the result of
      brain dispositional factors, but rather may be related to its reduced inhibition
      of the norepinephrine transporter, perhaps altering the interaction of
      dopaminergic and noradrenergic neural systems.

PMID- 17218797
TI  - Runway self-administration of intracerebroventricular cocaine: evidence of mixed
      positive and negative drug actions.
AB  - In previous work from our laboratory, animals running for intravenous cocaine
      developed a unique approach-avoidance 'retreat behavior' that was hypothesized to
      result from cocaine's well documented reinforcing (positive) and anxiogenic
      (negative) properties. To assess the role of central mechanisms in producing
      cocaine's positive and negative effects, we assessed whether or not animals
      running a straight alley for intracerebroventricular applications of cocaine
      would produce a similar behavioral profile to that previously observed with
      intravenous applications. Retreat frequency and location were measured in male
      Sprague-Dawley rats trained to run an alley for one of four doses of
      intracerebroventricular-administered cocaine (0, 25, 50 or 100 microg
      cocaine/infusion). Testing involved a single trial per day over 14 consecutive
      days with a single infusion of cocaine delivered upon goal box entry. The 100 and
      50 microg intracerebroventricular cocaine groups exhibited significantly higher
      retreat frequencies than the 25 and 0 microg groups and the nature and magnitude
      of the behavior was comparable to that previously observed with intravenous
      cocaine. These results suggest that the intracerebroventricular self
      administration of cocaine results in mixed positive and negative consequences and
      therefore likely stem from the drug's actions within the central nervous system.

PMID- 17218798
TI  - The effects of anorexic drugs on free-fed rats responding under a second-order
      FI15-min (FR10:S) schedule for high incentive foods.
AB  - Many similarities exist between the overconsumption of food, which results in
      obesity, and drug addiction. The present study investigated the effects of
      anorectic drugs on responding maintained by high incentive, but nutritionally
      unnecessary, food reinforcers using an FI15(fixed-ratio 10:S) schedule of
      reinforcement, similar to that used in studies on the incentive properties of
      drugs of abuse. Rats were trained to respond on a lever to gain access to two
      high incentive foods--chocolate chip cookies and cheese. Under the FI15(FR10:S)
      schedule, every 10th response (fixed-ratio 10) delivered a tone and light
      conditioned stimulus. The first ratio completed 15 min after the start of the
      session produced the conditioned stimulus and opened a door to give access to a
      piece of cookie. After 5 min to consume the high incentive food, a second 15-min
      interval was started, terminating in access to a second reinforcer, cheese. Once
      trained, the rats were given free access to laboratory chow in the home cage.
      They continued to work for the high incentive foods for a period of over 1 year,
      showing a pattern of responding appropriate to an FI(fixed-ratio) schedule.
      Naloxone (1.0 mg/kg), fenfluramine (1 and 2 mg/kg), D-amphetamine (0.25 and 0.5
      mg/kg), and rimonabant (3 mg/kg) significantly reduced responding, especially in
      the second interval. In contrast, complete removal of the high incentive food
      from the test procedure did not immediately reduce the rate of responding,
      tending to increase it in the second of the intervals. Apparently, the drugs did
      not reduce responding by reducing the experienced magnitude of the high incentive
      food, but more probably by reducing the animals' motivation.

PMID- 17218799
TI  - Gabapentin does not reduce smoked cocaine self-administration: employment of a
      novel self-administration procedure.
AB  - Previously, we reported that gabapentin, a nonselective gamma-aminobutyric acid
      agonist, reduced 'positive' subjective effects of cocaine without reducing
      cocaine self-administration. We speculated that the self-administration procedure
      used in that study was not sensitive to subtle shifts in the reinforcing effects
      of cocaine. Thus, this study examined the effects of gabapentin maintenance on
      cocaine self-administration using a purchase-cocaine choice procedure. During
      this 48-day inpatient/outpatient study, nontreatment-seeking cocaine abusers (n =
      12) were maintained on gabapentin (0, 600, 1200 mg/day); four doses of cocaine
      (0, 12, 25, 50 mg) were each tested twice under each gabapentin condition. All
      cocaine testing was conducted while participants were inpatients. Before the
      start of each session, participants were provided with 25 dollars (five 5 dollar
      bills, one for each choice opportunity) and smoked the 'sample' cocaine dose
      once. Subsequently, participants were given five opportunities to purchase the
      sampled dose of cocaine (at 5 dollars per dose) or to keep 5 dollars for that
      choice trial. Choice to self-administer cocaine increased significantly with
      escalating cocaine doses; gabapentin maintenance did not alter choice to self
      administer cocaine. These results concur with findings from our previous
      investigations of gabapentin and with those from a clinical trial examining the
      effects of larger gabapentin doses on cocaine use by treatment-seeking cocaine
      dependent individuals. Together, the data indicate that gabapentin does not show
      promise as a treatment medication for cocaine dependence.

PMID- 17218800
TI  - Lithium's effect in forced-swim test is blood level dependent but not dependent
      on weight loss.
AB  - The effects of lithium in models of depression are often inconsistent. We aimed
      to replicate a regimen that induces robust antidepressant effects in the forced
      swim test. Mice were treated with three different doses of lithium chloride
      (LiCl) 0.25, 0.4 or 0.5% in food and the forced-swim test or open field test was
      performed on day 15. We yoked control mice to food deprivation to test whether
      lithium-induced food deprivation could cause the lithium effects in the forced
      swim test. Treatment with LiCl doses leading to blood levels of 1.3 and 1.4
      mmol/l led to highly significant reduction in immobility time in the forced-swim
      test, but the dose leading to a blood level of 0.8 mmol/l was not different from
      controls in immobility time. Mice yoked to lithium-induced food deprivation
      showed no difference in the forced-swim test compared with controls. In
      conclusion these results suggest that lithium effects in mice in the forced-swim
      test are dose dependent but not owing to lithium-induced weight loss.

PMID- 17218803
TI  - Inflammatory mechanisms in allergic rhinitis.

PMID- 17218801
TI  - Pharmacological analysis of the effects of benzodiazepines on punished schedule
      induced polydipsia in rats.
AB  - Food-deprived Wistar rats were exposed to a fixed-time 60-s food delivery
      schedule until they developed schedule-induced polydipsia. Every fifth lick was
      then followed by an electric shock during two, signalled, 5-min periods, which
      ran concurrently with the food delivery schedule. Shock intensities were adjusted
      to reduce licking to 60-70% of the unpunished licking rates. The benzodiazepine
      full agonists, diazepam (0.3-3.0 mg/kg), chlordiazepoxide (0.3-10.0 mg/kg),
      oxazepam (0.3-3.0 mg/kg) and the benzodiazepine partial agonist, RU-32698 (3.0
      17.0 mg/kg), led to increases in punished responding at intermediate doses and
      decreases at the highest doses tested. All benzodiazepine agonists brought about
      dose-dependent decreases in unpunished schedule-induced polydipsia, with doses
      required to reduce drinking proving higher than doses required to increase
      punished schedule-induced polydipsia. The antipunishment effect of 0.3 mg/kg of
      diazepam was dose-dependently antagonized by flumazenil and the benzodiazepine
      inverse agonist, RU-34000. Flumazenil effects, however, could reflect actions of
      flumazenil as a partial inverse agonist at GABAA receptors. RU-32698 at 10.0
      mg/kg further facilitated the rate-increasing effect of 0.3 mg/kg of diazepam,
      but at 17.0 mg/kg partially blocked such antipunishment effect. Overall, the
      present results extend the similarities of the effects of benzodiazepine
      compounds on adjunctive and operant patterns of behaviour by showing similar
      interactions within the benzodiazepine receptor complex.

PMID- 17218804
TI  - Mucociliary clearance--a critical upper airway host defense mechanism and methods
      of assessment.
AB  - PURPOSE OF REVIEW: Mucociliary clearance is a critical host defense mechanism of
      the airways. Effective mucociliary clearance requires appropriate mucus
      production and coordinated ciliary activity. The important role of these two
      components is best demonstrated in disorders such as primary ciliary dyskinesia
      and cystic fibrosis, both of which lead to lifelong recurrent respiratory tract
      infections. We review the methods used to analyze mucociliary clearance. RECENT
      FINDINGS: Utilization of microdialysis probes has improved temporal resolution of
      mucociliary clearance in murine airways, availing many genetic mouse models to
      critical mucociliary clearance analysis, while improved fixation technique for
      transmission electron microscopy has allowed for detailed resolution of the
      airway surface liquid. High-speed digital video analysis has improved
      quantification of ciliary beat frequency while advancements in air-liquid
      interface culturing techniques have generated in-vitro models to investigate
      mucociliary clearance. SUMMARY: Advancements in techniques for analysis of
      mucociliary clearance have improved our understanding of the interaction between
      the respiratory epithelium and the airway surface liquid, resulting in the
      ability to study pathologic processes involving mucociliary clearance in great
      detail.

PMID- 17218805
TI  - Use of diagnostic algorithms and new technologies to study the incidence and
      prevalence of viral upper respiratory tract infections and their complications in
      high risk populations.
AB  - PURPOSE OF REVIEW: Most studies on the natural history of viral upper respiratory
      tract infections and their complications rely for ascertainment on self-assessed
      cold/flu illness or the identification of presumed complications. The criteria
      for cold/flu definition, however, are variable within and between individuals and
      illness is not prerequisite for a viral upper respiratory tract infection. These
      factors bias estimates of the incidence and prevalence of viral upper respiratory
      tract infections and their complications. Here we review new methodologies that
      can be adapted for use in future studies to refine those estimates. RECENT
      FINDINGS: We present a theoretical basis for standardized assignment of cold/flu
      episodes using a minimal algorithm template that operates on a structured set of
      symptoms/signs. We emphasize the greater accuracy of information derived from
      longitudinal studies that incorporate identification algorithms and assay of
      nasal secretions for causal virus by polymerase chain reaction and for
      proinflammatory chemicals to confirm nasal inflammation. SUMMARY: The
      methodologies and sampling strategies that we describe hold promise for better
      characterizing the incidence of complications for symptomatic and asymptomatic
      expressions of a viral upper respiratory tract infection caused by specific
      viruses. These data can then be used to estimate the efficacy and efficiency in a
      specified target population of prophylactic or intercurrent treatments to prevent
      the complications.

PMID- 17218806
TI  - The role of fungi in the airway of chronic rhinosinusitis patients.
AB  - PURPOSE OF REVIEW: To analyze the role of fungi in the upper and lower airway in
      chronic rhinosinusitis patients. RECENT FINDINGS: Recently, the involvement of
      the lower airway (as asthma, small airway disease and bronchial
      hyperresponsiveness) in chronic rhinosinusitis patients had been documented.
      Fungal spores after inhalation are submerged in the aqueous lining layers of the
      airway. The site depends on the size of the inhaled spores. The process of
      inhalation, retention and clearance of fungal spores may explain the positive
      culture results in both normal subjects and in most chronic rhinosinusitis
      patients. Fungal culture of different parts of the upper and lower airway in
      chronic rhinosinusitis patients had no correlation with cellular changes (local
      eosinophilia) and other clinical parameters. In chronic rhinosinusitis, with
      persistence of the chronic inflammatory process, the cells may be activated
      nonspecifically. SUMMARY: The role played by fungi in most chronic rhinosinusitis
      patients as the target antigen of initiation of such chronic inflammation is
      still debated. With the presence of chronic eosinophilic inflammation in chronic
      rhinosinusitis, an exaggerated reaction to various inhaled antigens is
      anticipated. The role of fungi will be confirmed only when T cells within the
      sinuses are shown to be actively responding to fungal antigens cultured from the
      sinus and with the demonstration that their elimination will stop the disease.

PMID- 17218807
TI  - Exhaled bronchial cysteinyl leukotrienes in allergic patients.
AB  - PURPOSE OF REVIEW: To review the current knowledge of noninvasive monitoring of
      allergic airway inflammation by analysis of leukotrienes in the exhaled breath
      condensate. RECENT FINDINGS: Treatment of respiratory allergies involves chronic
      treatment based on clinical symptoms and pulmonary function tests. Evaluation of
      local inflammation would be desirable but is currently not feasible because of
      the difficulty in sampling the airways. Recently, exhaled breath condensate
      collection and analysis has polarized much interest in the respiratory field.
      Although some methodological issues are still under scrutiny, airways
      inflammatory markers can be assayed with this technique. In particular, exhaled
      breath condensate leukotrienes have been thoroughly investigated in the setting
      of bronchial asthma and allergic rhinitis in adults and children. Exhaled
      leukotrienes are increased in patients with asthma and rhinitis during the pollen
      season, correlate with exacerbations and asthma severity, and are reduced by
      specific anti-inflammatory treatment and allergen avoidance. SUMMARY: Some issues
      still prevent the use of exhaled breath condensate in clinical practice but in
      the research setting it has been proved to be useful for noninvasive monitoring
      of allergic inflammation in the lung. In particular, exhaled leukotrienes may
      represent valuable biomarkers for diagnostic and therapeutic purposes in allergic
      patients.

PMID- 17218808
TI  - Codeine and cough: an ineffective gold standard.
AB  - PURPOSE OF REVIEW: Cough is one of the most common reasons why patients visit
      physicians. The opioid codeine has been a mainstay in the treatment of cough for
      decades and this drug is widely regarded as the 'gold standard' cough
      suppressant. RECENT FINDINGS: Recent placebo-controlled studies have shown that
      codeine is no more effective than placebo in suppressing cough caused by either
      upper respiratory disorders or chronic obstructive pulmonary disease. These
      recent reports are not consistent with several older placebo-controlled studies
      that demonstrated the efficacy of codeine. The reasons for this difference are
      not fully understood. SUMMARY: We propose that these differences, as well as
      results from animal models, can be explained by the existence of a complex
      hierarchical control system that regulates the expression of coughing. This
      system, known as a holarchy, is composed of regulatory elements known as 'holons'
      that interact with one another to regulate cough. Based on work in animal models,
      codeine is proposed to act on an intermediate order holon that may not be
      critical for coughing under some situations in humans. Testing of this hypothesis
      and further elucidation of the control system for cough will represent an
      important direction for future research in this area.

PMID- 17218809
TI  - A review of voice and upper airway function in chronic cough and paradoxical
      vocal cord movement.
AB  - PURPOSE OF THE REVIEW: Chronic cough and paradoxical vocal fold movement (PVFM)
      are perplexing conditions. This paper reviews the recent literature in relation
      to the nature of PVFM and chronic cough and the management of symptoms associated
      with these disorders. RECENT FINDINGS: There are similarities in the voice and
      upper airway symptoms in chronic cough and PVFM. Clinically significant voice
      symptoms are present in approximately 40% of individuals with chronic cough and
      PVFM and are similar to those occurring in voice disorders such as muscle tension
      dysphonia. Chronic cough can be associated with PVFM in a large proportion of
      cases. Extrathoracic airway hyperresponsiveness is a common underlying mechanism
      in PVFM and chronic cough. Speech pathology intervention can be effective in
      controlling symptoms in chronic cough, which suggests that the anatomic
      diagnostic protocol could be expanded to incorporate this intervention. Chronic
      cough that fails to respond to medical management should be conceptualized as
      either due to PVFM or idiopathic. PVFM and chronic cough are not necessarily the
      result of underlying psychopathology. SUMMARY: Chronic cough and PVFM manifest in
      a range of clinically significant voice and upper airway symptoms. The anatomic
      diagnostic protocol used in the management of chronic cough could be expanded to
      include PVFM as a potential cause of cough, and speech pathology intervention as
      treatment for chronic cough.

PMID- 17218810
TI  - The reclassification of asthma based on subphenotypes.
AB  - PURPOSE OF REVIEW: Despite asthma being widely regarded as a heterogeneous
      disease, a consensus for an accurate system of classification has not been
      agreed. Recent studies have suggested that the recognition of subphenotypes of
      asthma based on the pattern of airway inflammation may be particularly useful in
      increasing our understanding of the disease. The present review discusses the
      important literature in this field, placing current work in its historical
      context. RECENT FINDINGS: The use of noninvasive markers of airway inflammation
      has suggested the presence of four distinct phenotypes: eosinophilic,
      neutrophilic, mixed inflammatory and paucigranulocytic asthma. Recent studies
      suggest that these subgroups may differ in their aetiology, immunopathology and
      response to treatment. Several studies have focused on refractory asthma as a
      distinct phenotype with evidence of a more distal pattern of airway inflammation
      and of upregulation of the tumour necrosis factor-alpha axis. Finally, novel
      treatment approaches targeted at specific patterns of airway inflammation are
      emerging, making an appreciation of subphenotypes particularly relevant. SUMMARY:
      The present review will discuss limitations to current classification systems,
      identify key current studies based on identifying inflammatory subphenotypes and
      provide suggestions for a novel approach that may further improve our
      understanding in this area.

PMID- 17218811
TI  - Manipulation of signaling to control allergic inflammation.
AB  - PURPOSE OF REVIEW: Inflammatory mediators produced from activated mast cells and
      T helper type 2 cells drive allergic inflammation. The pathways required for mast
      and T helper type 2 cell activation and the effects of their products are being
      defined in order to identify new therapeutics. We focus on recent findings on the
      chief inducer of mast cell activation, the IgE receptor-signaling cascade, and
      the development of new inhibitors of this pathway. We also summarize work that
      examines the molecular mechanisms utilized by the interleukin IL-4/13 receptors
      and characterizes therapeutic compounds that target these pathways. RECENT
      FINDINGS: The tyrosine kinases Lyn, Fyn and Syk have complex roles in IgE
      receptor signaling. Biochemical analysis and gene expression profiling have shed
      light on both the positive and negative functions of these proteins and establish
      additional connections with downstream pathways. Syk inhibitors were identified
      that may prove useful as antiinflammatory agents. Progress has been made in
      characterizing how IL-4/13 interact with their cognate receptors that will aid in
      the design of inhibitors of these interactions. SUMMARY: Recent studies have
      advanced our understanding of how the IgE receptor and IL-4/13 receptors
      function. This new knowledge may lead to the development of novel and highly
      specific inhibitors of allergic inflammation.

PMID- 17218812
TI  - Innate immune mucin production via epithelial cell surface signaling:
      relationship to allergic disease.
AB  - PURPOSE OF REVIEW: Airway epithelial surface signaling is provided by epidermal
      growth factor receptor (EGFR) phosphorylation, resulting in innate immune
      responses. Here the focus is the EGFR cascades leading to immune mucin responses.
      The review is timely because recent discoveries implicate these pathways in
      multiple innate immune defenses in addition to mucin production. RECENT FINDINGS:
      EGFR activation causes mucin production and inhibition prevents mucin production
      by multiple stimuli. The receptors and their epithelial-bound proligands are
      examined. Proteases cleave and release soluble ligand, which then activates EGFR.
      A surface metalloprotease, tumor necrosis factor alpha-converting enzyme (TACE),
      modulates proligand release (and thus EGFR activation). TACE is activated by
      reactive oxygen species, which can be produced by a novel molecule, dual oxidase
      1, which provides reactive oxygen species for TACE cleavage. Upstream of dual
      oxidase-1 are epithelial receptors that receive messages from inhaled irritants
      and stimulate the dual oxidase-1-TACE-ligand-EGFR cascade. SUMMARY: The EGFR
      surface signaling pathways are reviewed, with the focus on mucin production,
      involving human airway epithelial cultures and animal studies, including relevant
      studies of asthma in humans. Future studies may broaden the innate defenses and
      utilize these surface signaling pathways in various epithelia, with a variety of
      pathophysiologic stimuli, with the ultimate aim of examining these pathways in
      inflammatory diseases.

PMID- 17218813
TI  - The role of epithelial injury and repair in the origins of asthma.
AB  - PURPOSE OF REVIEW: We currently understand little about the mechanisms that lead
      to asthma. The bronchial epithelium is the first cell layer of contact with the
      environment and as such is an especially attractive target in which to identify
      novel mechanisms and new therapeutic strategies in disease development. We
      discuss the role of epithelial injury and wound repair in the origins of asthma.
      RECENT FINDINGS: The presence of inflammation, thickening of the basement
      membrane and angiogenesis have been described in bronchial biopsies from
      asthmatic children. We and others have demonstrated the utility of bronchial
      brushings from children for the isolation, characterization and culture of
      primary epithelial cells. The results of these experiments suggest that intrinsic
      differences exist between asthmatic and nonasthmatic epithelial cells. SUMMARY:
      It is becoming increasingly clear from studies involving adults and, more
      recently, children, that the epithelium orchestrates inflammatory and remodeling
      responses of the airway. Equally clear is that the asthmatic epithelium responds
      inappropriately to challenge and displays signs of dysregulated repair.
      Understanding the regulatory mechanisms involved in these processes, including
      the role of resident/recruited progenitor cells, is crucial if we are to halt the
      progression of asthma when the disease first manifests in childhood.

PMID- 17218814
TI  - Identifying novel genes contributing to asthma pathogenesis.
AB  - PURPOSE OF REVIEW: To illustrate recent examples of novel asthma genes such as
      those encoding G-protein-coupled receptor for asthma susceptibility, filaggrin
      and tenascin-C, and to describe the process that is needed to translate these
      findings to the clinic. RECENT FINDINGS: Many hundreds of studies have been
      published investigating the association of genetic polymorphisms in candidate
      genes with asthma. These genes were selected on the basis of the gene's product
      known involvement in the disease process. Moreover, it is the identification of
      novel genes through hypothesis-independent approaches such as genome-wide linkage
      studies that is likely to radically alter our understanding of asthma
      pathophysiology. The identification of a gene is, however, only the first step in
      a long process that may eventually lead from gene to treatment. This process
      includes replication, functional studies and, finally, intervention studies.
      SUMMARY: While significant progress has been made in the identification of asthma
      susceptibility genes, it is clear that issues such as replication and functional
      characterization mean that considerably more research is required. This may
      enable us to realize benefits to patient treatment that studies of the genetic
      basis of asthma have the potential to deliver.

PMID- 17218815
TI  - Gene-environmental interaction in asthma.
AB  - PURPOSE OF REVIEW: Asthma is likely to result from the effects of environmental
      stimuli in genetically susceptible individuals. This review summarizes recent
      studies of gene-environmental interaction in the pathogenesis of asthma, focusing
      on study designs. RECENT FINDINGS: Studies using genetic epidemiology, in-vitro
      and ex-vivo models and in-vivo model organisms demonstrate that gene
      environmental interaction in involved in the development of asthma. Genetic
      association studies show a reduced risk of asthma and atopy with early life
      exposure to farming environments and house dust endotoxin, and increased risk
      with environmental tobacco smoke. These associations are modified by CD14
      genotype. In people with a specific genotype, high environmental exposure may
      have the opposite effect of low exposure, possibly explaining some of the
      inconsistencies in previous studies. In-vitro and ex-vivo cell culture
      experiments show gene-environmental interactions with Toll-like receptor
      agonists, viruses and tobacco smoke. Interactions between innate immunity genes
      and exposure to endotoxin and air pollution have been observed in in-vivo mouse
      models. SUMMARY: The expanding evidence for gene-environmental interaction in
      asthma indicates the importance of measuring environmental factors in genetic
      studies of asthma. Understanding gene-environmental interaction would facilitate
      risk prognostication, improve preventive strategies and develop targeted
      interventions in people with asthma.

PMID- 17218816
TI  - The early-life origins of asthma.
AB  - PURPOSE OF REVIEW: Early-life events are pivotal in determining adult lung
      function and disease, and the prognosis of preschool wheeze is determined by gene
      environment interactions, antenatally and in the first 3 years of life. RECENT
      FINDINGS: Birth cohort studies show that lung function tracks from the first 3
      years of life into adolescence and probably beyond. Umbilical-cord-blood studies
      demonstrate that the immunological responses to viral infections are in part
      determined antenatally. The neutrophil not the eosinophil is the key effector
      cell in preschool wheeze. Allergic sensitization in the first 3 years of life is
      key to subsequent prognosis. Histological changes develop in the airway after the
      onset of symptoms, but by school age the full-blown airway pathology of atopic
      asthma is present. Although novel genes such as ADAM33 studied in isolation are
      of interest, unless gene expression is studied in the context of the environment,
      misleading conclusions will be reached. We need disease-modifying therapy;
      inhaled steroids do not prevent progression from intermittent to persistent
      wheeze. SUMMARY: The first 3 years of life are pivotal in determining lung
      function and prognosis of wheeze, probably throughout life. Further research
      requires focused hypotheses encompassing genes and the environment in which they
      are expressed.

PMID- 17218817
TI  - Respiratory viruses in childhood asthma.
AB  - PURPOSE OF REVIEW: Several epidemiological studies have confirmed the association
      between viral respiratory infections and wheezing episodes or exacerbations of
      asthma in childhood. In contrast, whether particular viral infections can be
      protective or able to initiate asthma is still debated; recent studies reported
      herein have added to our understanding in several different domains, including
      natural history, virology and mechanisms. RECENT FINDINGS: Animal studies support
      the possibility that severe infections with respiratory syncytial virus early in
      life may be able to diverge the immune response towards an allergic phenotype;
      however, in human studies, predisposition seems dominating. Human rhinoviruses
      are increasingly being shown to be equally important as respiratory syncytial
      virus even in infancy. Newly discovered respiratory viruses have also been
      associated with asthma exacerbations. The interferon pathway is currently
      scrutinized with respect to virus-induced inflammation; furthermore, indications
      that viral infections may be associated with remodeling phenotypes have been
      recently published. SUMMARY: Notwithstanding the progress in epidemiology and
      pathogenesis of virus-induced asthma, more effort is needed in assessing possible
      strategies for treatment. Current treatments seem to be relatively ineffective,
      but new pathways give a hopeful message for future therapies.

PMID- 17218819
TI  - Quantitative sputum cell counts as a marker of airway inflammation in clinical
      practice.
AB  - PURPOSE OF REVIEW: Bronchitis, meaning airway inflammation, is an important
      component of airway disease. Yet respirologists and allergists, who have stressed
      the importance of measurements of airway function, have been slow to introduce
      airway inflammation measurements into clinical practice. Of the measurements
      available, quantitative sputum cell counts have the most clinical value. This
      article provides additional information on this topic from studies published in
      2005 and 2006. RECENT FINDINGS: Airway diseases are heterogeneous within patients
      in terms of the disease present and the type of airway inflammation. Quantitative
      sputum cell counts (total cell count as well as the differential) identify
      noneosinophilic, mainly neutrophilic, probably infective exacerbations as common
      in patients with asthma and chronic obstructive pulmonary disease that may be
      unresponsive to corticosteroid treatment. In contrast, measurements of sputum
      eosinophils can be used to guide the minimum dose of corticosteroid required to
      control eosinophilic bronchitis and reduce eosinophilic exacerbations. SUMMARY:
      Measurements of quantitative sputum cell counts need to be made available,
      initially by tertiary care centres, to diagnose bronchitis in airway disease and
      to optimize treatment. Examination of how these are complemented by indirect
      measures of airway inflammation, specifically exhaled nitric oxide and airway
      hyperresponsiveness to stimuli acting indirectly through mediator release,
      requires further investigation.

PMID- 17218818
TI  - New insights into occupational asthma.
AB  - PURPOSE OF REVIEW: To examine recent publications on the types of agents involved
      in occupational asthma, the mechanisms by which they induce asthma, and how best
      to evaluate and treat workers suspected of this respiratory condition. RECENT
      FINDINGS: High rates of occupational asthma and inhalation accidents were found
      in workers in crafts and related occupations in the manufacturing industries, and
      in plant and machine operatives; cleaners and construction workers may also be at
      risk. Further data support a role for CD4 T cells in low-molecular-weight agent
      induced asthma, such as with isocyanates, and neurogenic mechanisms may also be
      involved. The use of noninvasive measures of airway inflammation in the diagnosis
      and management of occupational asthma such as sputum eosinophils monitoring is
      promising, although this is less obvious for exhaled nitric oxide. Finally, the
      persistence of troublesome asthma even after withdrawal from relevant exposure
      has been re-emphasized and surveillance programs have been proposed. SUMMARY:
      Further data have been gathered on the prevalence of occupational asthma in
      various working populations, its mechanisms of development, the contribution of
      noninvasive measures of airway inflammation in the diagnosis and management of
      this condition, and its management and prevention.

PMID- 17218820
TI  - Magnesium in the treatment of asthma.
AB  - PURPOSE OF REVIEW: To provide an update of recent research on the role of
      magnesium in the management of asthma. RECENT FINDINGS: Further evidence has been
      published that long-term oral magnesium supplementation does not lead to improved
      control in adult asthma. In contrast, updated meta-analyses of randomized
      controlled trials have confirmed the efficacy of both intravenous and inhaled (as
      an adjuvant to salbutamol nebulizer solution) magnesium therapy in severe asthma.
      This conclusion is still limited by the paucity of randomized controlled trials,
      however, with many issues yet to be firmly established, such as the efficacy in
      different patient subgroups, the dose regimes, and the optimal method of
      administration. International guidelines currently recommend the use of
      intravenous magnesium in severe asthma, and there is evidence that this approach
      is now widely used in emergency departments in North America. This audit also
      illustrated the emerging unregistered use of nebulized magnesium/salbutamol
      solution. SUMMARY: Further investigation of the efficacy and safety of magnesium
      in severe asthma is now urgently required to determine its role in this clinical
      situation. The research community must heed the call for more research that is
      being made by funding agencies dealing with this area.

PMID- 17218821
TI  - Bibliography. Current world literature. Upper airway disease.

PMID- 17218823
TI  - Nutritional evidence still lacks consistency.

PMID- 17218824
TI  - Dietary glycemic load, whole grains, and systemic inflammation in diabetes: the
      epidemiological evidence.
AB  - PURPOSE OF REVIEW: The aim of this article is to present recent findings from
      epidemiological studies on the effects of dietary glycemic load and whole grain
      foods on systemic inflammation in diabetic patients and to postulate potential
      mechanisms. RECENT FINDINGS: Diets low in glycemic index/load or high in whole
      grain products have been associated with decreased concentrations of inflammatory
      markers and increased adiponectin levels among diabetic patients. These
      associations appear to be independent of body weight, glycemic control, and other
      cardiovascular risk factors. The protective effects of low glycemic load and high
      whole grains on systemic inflammation may be explained, in part, by reduction in
      hyperglycemia-induced overproduction of oxidative stress and by amelioration in
      insulin resistance, adiposity, dyslipidemia, and hypertension. SUMMARY: Diets low
      in glycemic load and high in whole grains may have a protective effect against
      systemic inflammation in diabetic patients. Such diets can be recommended to
      diabetic patients for the prevention of cardiovascular complications.

PMID- 17218825
TI  - Carbohydrates: is the advice to eat less justified for diabetes and
      cardiovascular health?
AB  - PURPOSE OF REVIEW: Recent randomized controlled trials examining diets of varying
      carbohydrate composition recommended for people with diabetes and cardiovascular
      disease and those at risk are summarized. RECENT FINDINGS: Severe carbohydrate
      restriction results in appreciable initial weight loss and improvement in risk
      factors. After a year, however, the beneficial effects are equal to or less than
      those achieved on conventional alternatives. Some people develop elevations of
      LDL cholesterol. Modest carbohydrate restriction with relatively high intakes of
      cis-unsaturated fatty acids and protein is acceptable to many people and is more
      likely to produce sustained benefit in terms of weight loss and cardiovascular
      risk indicators. SUMMARY: Diets involving moderate carbohydrate restriction are
      suitable alternatives to high-carbohydrate, high-fibre diets for weight loss and
      reduction of cardiovascular disease and diabetes risk, as well as to treat
      individuals with the conditions. As such diets are generally high in protein and
      unsaturated fatty acids, they are not recommended for those with established or
      incipient nephropathy. High-carbohydrate, high-fibre diets remain appropriate for
      use in all those situations, provided carbohydrate is derived principally from
      minimally processed wholegrain breads and cereals and intact vegetables and
      fruit. Lower carbohydrate options may be preferable for markedly insulin
      resistant individuals.

PMID- 17218826
TI  - Coffee, caffeine, and coronary heart disease.
AB  - PURPOSE OF REVIEW: This review summarizes and highlights recent advances in
      current knowledge of the relationship between coffee and caffeine consumption and
      risk of coronary heart disease. Potential mechanisms and genetic modifiers of
      this relationship are also discussed. RECENT FINDINGS: Studies examining the
      association between coffee consumption and coronary heart disease have been
      inconclusive. Coffee is a complex mixture of compounds that may have either
      beneficial or harmful effects on the cardiovascular system. Randomized controlled
      trials have confirmed the cholesterol-raising effect of diterpenes present in
      boiled coffee, which may contribute to the risk of coronary heart disease
      associated with unfiltered coffee consumption. A recent study examining the
      relationship between coffee and risk of myocardial infarction incorporated a
      genetic polymorphism associated with a slower rate of caffeine metabolism and
      provides strong evidence that caffeine also affects risk of coronary heart
      disease. Several studies have reported a protective effect of moderate coffee
      consumption, which suggests that coffee contains other compounds that may be
      beneficial. SUMMARY: Diterpenes present in unfiltered coffee and caffeine each
      appear to increase risk of coronary heart disease. A lower risk of coronary heart
      disease among moderate coffee drinkers might be due to antioxidants found in
      coffee.

PMID- 17218827
TI  - Nutritional effects on blood pressure.
AB  - PURPOSE OF REVIEW: There has not been a thorough recent evaluation of the
      nutritional effects on blood pressure. Apart from outstanding clinical trials
      like Dietary Approaches to Stop Hypertension, there have been controversial
      papers on a number of factors influencing blood pressure. This paper is a
      systematic review of the current literature as it relates to hypertension. RECENT
      FINDINGS: Results from many meta-analyses and well controlled clinical trials on
      the effects of a variety of nutritional factors are presented in this review.
      Evidence suggests that dietary sodium intake needs reduction. There is a
      seemingly inverse relationship between protein intake and blood pressure, but
      data are inconclusive. High monounsaturated fat and fish oil appear to be
      beneficial. Several studies on dietary fiber indicate that the strongest evidence
      for blood pressure lowering effects is in hypertensive as opposed to normotensive
      participants. Vegetarians seem to have lower levels of hypertension and
      cardiovascular disease risk. Low carbohydrate diets show short-term beneficial
      effects but are not sustained. High levels of potassium, magnesium, calcium and
      soy seem to have some benefit, but results remain inconclusive. Weight reduction
      positively impacts blood pressure. SUMMARY: More compelling research defining
      specific factors is needed to inform the public as to steps needed to reduce
      blood pressure and improve cardiovascular risk.

PMID- 17218828
TI  - Edible nuts and metabolic health.
AB  - PURPOSE OF REVIEW: This review summarizes evidence for metabolic health benefits
      of tree nuts and groundnuts (peanuts). While a role for nuts in the dietary
      management of LDL-cholesterol is well established, it is evident that regular
      consumption of nuts may also help to counteract other cardiovascular and
      metabolic risk factors. RECENT FINDINGS: Nuts are not only energy dense foods,
      they are rich sources of monounsaturated and polyunsaturated fatty acids and
      other bioactive nutrients with important metabolic effects. Contrary to
      expectations, epidemiological studies indicate that regular consumption of nuts
      is unlikely to contribute to obesity or increased risk of diabetes. In fact, it
      may help to regulate body weight by suppressing appetite and fat absorption. Nut
      consumption counteracts dyslipidemia and has the capacity to improve circulatory
      function through the actions of multiple constituents (arginine, polyphenols) on
      endothelial mechanisms. SUMMARY: Nuts are densely packaged nutrients with wide
      ranging cardiovascular and metabolic benefits, which can be readily incorporated
      in healthy diets. Their potential role in counteracting obesity and the metabolic
      syndrome warrants further investigation.

PMID- 17218829
TI  - Omega-3 fatty acids and prevention of arrhythmias.
AB  - PURPOSE OF REVIEW: There is now a considerable factual basis from laboratory and
      clinical trials that omega-3 fatty acids of fish oil will prevent fatal
      arrhythmias in animals and humans and this is the focus of the review. RECENT
      FINDINGS: Several recent trials in humans have strengthened the evidence that
      omega-3 fatty acids may prevent arrhythmias although this has not been a uniform
      finding. SUMMARY: Since there are at present some 400 000 deaths annually in the
      US alone and millions more worldwide, what has been learned about the
      antiarrhythmic actions of omega-3 fatty acids has considerable potential public
      health benefit.

PMID- 17218830
TI  - Phytosterols and vascular disease.
AB  - PURPOSE OF REVIEW: Phytosterols and stanols are plant derivatives that compete
      with cholesterol for intestinal absorption and thereby lower serum cholesterol
      concentrations. They have been developed as food additives to help lower serum
      cholesterol but there is concern that these additives could inadvertently
      increase cardiovascular risk. This concern arises from the observation that
      patients with the rare genetic condition phytosterolemia overabsorb phytosterols
      and develop premature atherosclerosis. This review evaluates the relationship
      between phytosterol and stanol supplementation and cardiovascular risk. RECENT
      FINDINGS: Plant sterol supplementation produces minimal increases in blood
      phytosterol concentrations in humans. Recent animal studies suggest that
      phytosterols reduce atherosclerosis in the Apo-E deficient mouse model. The
      evidence from human studies is mixed and does not prove or disprove an increase
      in atherosclerotic risk from serum phytosterol levels. An increase in risk seems
      unlikely, but additional studies should address this possibility. SUMMARY:
      Phytosterols are effective in lowering low-density lipoprotein-cholesterol
      levels, and do not appear to increase atherosclerotic risk, but additional
      research on this topic is necessary.

PMID- 17218831
TI  - Vitamin D and vascular calcification.
AB  - PURPOSE OF REVIEW: Vascular calcification is frequently found in patients with
      osteoporosis, atherosclerosis and chronic kidney disease, leading to high
      morbidity and mortality rates. The effects of vitamin D excess and deficiency on
      vascular calcification are reviewed in this article. RECENT FINDINGS: There is
      evidence from experimental studies that mediacalcinosis induced by vitamin D
      excess is an active and reversible process. Vitamin D excess, however, is rarely
      seen in the general human population. Experimental data also demonstrate that
      physiologic vitamin D actions include the inhibition of processes that are
      important for intimal and medial artery calcification such as pro-inflammatory
      cytokine release, adhesion molecule release, and proliferation and migration of
      vascular smooth muscle cells. In uremic rats, low levels of the vitamin D hormone
      calcitriol are associated with massive vascular and soft tissue calcifications.
      Whereas retrospective studies already indicate a beneficial effect of active
      vitamin D on mortality rates in chronic kidney disease, little is yet known about
      the effect of vitamin D deficiency on cardiovascular morbidity and mortality in
      the general population. SUMMARY: Available data indicate that vitamin D exerts a
      biphasic 'dose response' curve on vascular calcification with deleterious
      consequences not only of vitamin D excess but also of vitamin D deficiency.

PMID- 17218832
TI  - Physical activity, cardiorespiratory fitness and insulin resistance: a short
      update.
AB  - PURPOSE OF REVIEW: High levels of cardiorespiratory fitness and/or habitual
      physical activity are associated with reduced risk of cardiovascular disease. The
      responsible mechanisms are multifarious, but effects on insulin sensitivity are
      likely to play an important role. The purpose of this review is to highlight some
      recent evidence on the interrelationships between physical activity, fitness,
      obesity, genotype and insulin resistance. RECENT FINDINGS: Effects on
      cardiorespiratory fitness and abdominal obesity are both likely to contribute to
      the insulin-sensitizing effects of regular physical activity. Recent data suggest
      that at least in older adults, the intensity of an exercise intervention may
      influence the magnitude of changes in insulin sensitivity, and emerging data
      suggest that individual changes in insulin sensitivity following an exercise
      programme may, in part, be influenced by genotype. SUMMARY: Increasing physical
      activity reduces insulin resistance. As both intensity of exercise and genetic
      factors may modulate the magnitude of this effect, current physical activity for
      health guidelines that emphasize engagement in moderate-intensity physical
      activity in a 'one-size-fits-all' approach may need revision in the future to
      optimize the potential benefits accrued from individuals becoming more active.

PMID- 17218833
TI  - Is dietary restriction beneficial for human health, such as for immune function?
AB  - PURPOSE OF REVIEW: The impact of dietary restriction on physiologic function in
      humans is now beginning to be examined. The clinical trials are fueled by decades
      of animal experiments showing that dietary restriction delays the aging process
      and decreases the incidence of many age-associated diseases. The critical issue
      addressed in this article is whether or not dietary restriction long term is
      feasible or beneficial in humans. RECENT FINDINGS: Short-term dietary restriction
      in humans does appear to have beneficial effects at lowering metabolism,
      especially when examining carbohydrates and weight loss. Dietary restriction long
      term does, however, have detrimental psychological effects in humans, making its
      feasibility questionable. Even short-term dietary restriction can negatively
      impact physical activity and potentially some aspects of immunity. The best
      avenue for humans to benefit from dietary restriction would be for
      pharmacological or bioactive food ingredient mimetics to be developed which would
      be more applicable for long-term use. SUMMARY: Dietary restriction per se is
      unlikely to emerge as a feasible long-term strategy to improve human health.
      Developing dietary restriction mimetics targeting energy metabolism may prove
      beneficial, not only in aging, but also in diabetes and obesity.

PMID- 17218834
TI  - Reciprocal relationships between abnormal metabolic parameters and endothelial
      dysfunction.
AB  - PURPOSE OF REVIEW: Endothelial dysfunction plays a crucial role in the
      pathogenesis of atherosclerosis and related cardiovascular diseases.
      Glucotoxicity, lipotoxicity, and inflammation all independently contribute to
      development of both endothelial dysfunction and insulin resistance. We review
      pathophysiological mechanisms underlying reciprocal relationships between
      endothelial dysfunction and insulin resistance and recent insights from
      therapeutic interventions to improve both metabolic and vascular function. RECENT
      FINDINGS: Shared causal factors such as glucotoxicity, lipotoxicity, and
      inflammation interact at multiple levels creating reciprocal relationships
      between insulin resistance and endothelial dysfunction that help to explain
      frequent clustering of metabolic and cardiovascular disorders. Metabolic
      abnormalities implicated in the development of insulin resistance, including
      hyperglycemia, elevated levels of free fatty acids, accumulation of advanced
      glycation end products, dyslipidemias, and decreased levels of adiponectin, also
      contribute importantly to endothelial dysfunction. Diet, exercise, cardiovascular
      drugs, and insulin sensitizers simultaneously improve endothelium-dependent
      vascular function, reduce inflammation, and improve insulin sensitivity by both
      distinct and interrelated mechanisms. SUMMARY: Pathophysiological mechanisms
      underlying reciprocal relationships between endothelial dysfunction and insulin
      resistance contribute to clustering of metabolic and cardiovascular diseases
      represented by the metabolic syndrome. Therapeutic interventions that target
      endothelial dysfunction or insulin resistance often simultaneously improve both
      metabolic and vascular function.

PMID- 17218836
TI  - Bibliography. Current world literature. Nutrition and metabolism.

PMID- 17218835
TI  - Lipidomics and lipid profiling in metabolomics.
AB  - PURPOSE OF REVIEW: The field of metabolomics is extending the principles of
      genomics into cellular and organism metabolism and driving a revolution in lipid
      biochemistry, physiology and nutrition. Lipids studied using metabolomic
      approaches - lipidomics - are an ideal subject for metabolomic measurements.
      RECENT FINDINGS: Lipids are small molecules that share common physical and
      chemical properties as a class, whose presence and abundance are key to much of
      metabolic regulation, from subcellular compartments to whole body energy control
      and signaling. Furthermore, by measuring changes in lipid concentrations,
      scientists are gaining a more detailed understanding of biochemistry and thus
      annotating genomes, but also understanding genetic polymorphisms and the
      postgenetic effects induced by drugs, foods and toxins. SUMMARY: Although in its
      infancy - there are fewer than 200 total articles on lipidomics and metabolomics
      focusing on lipids - the field of metabolomics is beginning to deliver on its
      promise to revolutionize lipid and metabolic disease research.

PMID- 17218837
TI  - Nutrition and metabolism: food ingredients and health.

PMID- 17218838
TI  - Lipid metabolism: 5-lipoxygenase, 12/15-lipoxygenase, and atherogenesis.

PMID- 17218839
TI  - Nutrition and metabolism: cellular and extracellular antioxidant capacity and
      cardiovascular disease.

PMID- 17218840
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 17218841
TI  - Therapy and clinical trials.

PMID- 17218843
TI  - Ambivalency at the bedside: intraperitoneal chemotherapy.

PMID- 17218844
TI  - The distal fallopian tube: a new model for pelvic serous carcinogenesis.
AB  - PURPOSE OF REVIEW: Research over the past 50 years has yielded little concrete
      information on the source of pelvic serous cancer in women, creating a knowledge
      gap that has adversely influenced our ability to identify, remove or prevent the
      earliest stages of the most lethal form of ovarian cancer. RECENT FINDINGS: The
      distal fallopian tube is emerging as an established source of many early serous
      carcinomas in women with BRCA mutations (BRCA+). Protocols examining the fimbrial
      (SEE-FIM) end have revealed a noninvasive but potentially lethal form of tubal
      carcinoma, designated tubal intraepithelial carcinoma. Tubal intraepithelial
      carcinoma is present in many women with presumed ovarian or peritoneal serous
      cancer. A candidate precursor to tubal intraepithelial carcinoma, entitled the
      'p53 signature', suggests that molecular events associated with serous cancer
      (p53 mutations) may be detected in benign mucosa. SUMMARY: A fully characterized
      precursor lesion is a first and necessary step to pelvic serous cancer
      prevention. The emerging data offer compelling evidence for a model of 'fimbrial
      ovarian' serous neoplasia, and call attention to the distal fallopian tube as an
      important source for this disease, the study of which could clarify pathways to
      cancer in both organs and generate novel strategies for cancer prevention.

PMID- 17218845
TI  - Intestinal surgery in advanced ovarian cancer.
AB  - PURPOSE OF REVIEW: This review examines the current role of intestinal surgery in
      advanced ovarian cancer. Institutions differ considerably in surgical procedures
      and therapeutic outcomes for this disease. Moreover, therapeutic outcomes are
      influenced by the inclusion criteria for surgical procedures and the degree of
      surgical completion. We discuss the role of intestinal surgery and suggest
      surgical indications for intestinal surgery in advanced ovarian cancer. RECENT
      FINDINGS: Prognosis in advanced ovarian cancer is better when there is a smaller
      postoperative tumor mass. However, it is necessary to investigate the effects of
      intestinal surgery on residual tumor mass and its prognostic benefits. Here,
      recent reports were reviewed to ascertain the usefulness and safety of intestinal
      surgery for advanced ovarian cancer and examine surgical indications and
      institutional requirements. SUMMARY: By performing aggressive intestinal surgery
      such as combined bowel resection, optimal cytoreductive surgery can be performed
      in 70-98% of cases. The morbidity associated with intestinal surgery is
      acceptably low. Prognostic benefits for intestinal surgery are clear in patients
      with operable ovarian cancer with no residual disease. Women with suspected
      ovarian cancer should therefore be referred to centers with experienced tumor
      surgeons.

PMID- 17218846
TI  - Cytoreductive surgery for recurrent ovarian cancer.
AB  - PURPOSE OF REVIEW: The issue facing clinicians managing ovarian cancer has
      evolved over the past three decades from treatment for cure and subsequently
      palliation, to prolongation of survival for most patients. The purpose of this
      paper is to review the data, rationale, and issues surrounding cytoreductive
      surgery in recurrent ovarian cancer and its potential role in this new paradigm
      shift. RECENT FINDINGS: Abundant retrospective series report prolongation of
      survival with secondary cytoreductive surgery in recurrent ovarian cancer.
      Selection bias, publication bias, and subsequent therapies, however, are
      confounding factors for survival. As management of ovarian cancer has recently
      evolved to a treatment of a 'chronic disease', surgery (which has a definite role
      in primary therapy) should be considered. SUMMARY: No prospective randomized
      studies have been performed to date, and therefore adoption of this method of
      management has been limited. The absence of good data leaves clinicians without
      clear direction on how to best manage patients. Patients with favorable
      characteristics such as a long disease-free interval, good performance status, a
      single or few small intra-abdominal recurrences may benefit from secondary
      cytoreduction. A prospective randomized study is needed.

PMID- 17218847
TI  - Update on ovarian cancer screening.
AB  - PURPOSE OF REVIEW: Epithelial ovarian cancer is usually diagnosed in the advanced
      stage and carries a poor prognosis. When detected at an early stage, the 5-year
      survival rate is 90%. Despite the availability of various diagnostic tools for
      ovarian cancer screening, high levels of sensitivity and specificity are not
      achievable. There is therefore an ongoing need to identify new screening tests
      and strategies that should be readily available, relatively noninvasive, and
      achieve high sensitivity, specificity, and positive and negative predictive
      values. RECENT FINDINGS: Our review focuses on various screening technologies
      including serum biomarkers, transvaginal ultrasonography as well as multimodality
      screening that can be used for early detection of ovarian cancer. The efficacy of
      different screening tools is discussed along with the efforts made to improve
      sensitivity, specificity and positive predictive value. The initial results of
      two large population-based screening studies are presented. SUMMARY: An optimal
      screening test with high levels of sensitivity and specificity is indispensable
      for early detection of ovarian cancer. Serological screening with serum
      biomarkers (serum proteins and autoantibodies) can be used as a first-line
      screening test. In combination with TVS or color-flow Doppler imaging, this may
      prove very effective in early detection of ovarian cancer.

PMID- 17218848
TI  - Prophylactic oophorectomy in women at increased cancer risk.
AB  - PURPOSE OF REVIEW: Bilateral prophylactic salpingo-oophorectomy is widely used
      for cancer risk reduction in women with BRCA1/2 mutations. Bilateral prophylactic
      salpingo-oophorectomy significantly reduces breast cancer risk by approximately
      50% and ovarian cancer risk by 80-95% but may be accompanied by menopausal
      symptoms, impaired quality of life and accelerated bone loss. Therefore,
      decisions regarding the timing of bilateral prophylactic salpingo-oophorectomy
      and the use of post-bilateral prophylactic salpingo-oophorectomy hormone
      replacement therapy must be carefully considered. RECENT FINDINGS: Over the last
      year, studies have further examined issues related to quality of life associated
      with bilateral prophylactic salpingo-oophorectomy and have demonstrated that
      hormone replacement therapy following bilateral prophylactic salpingo
      oophorectomy in unaffected women does not negate the breast cancer risk reduction
      that bilateral prophylactic salpingo-oophorectomy provides. Studies have provided
      additional information on the residual risk of cancer following bilateral
      prophylactic salpingo-oophorectomy, have demonstrated its benefit in Lynch
      syndrome and have suggested a short-term mortality benefit following bilateral
      prophylactic salpingo-oophorectomy in BRCA1/2 mutation carriers. SUMMARY: We
      review the recent studies regarding bilateral prophylactic salpingo-oophorectomy
      and their implications for the clinical management of women who are at increased
      cancer risk.

PMID- 17218849
TI  - Racial/ethnic disparities in breast and gynecologic cancer treatment and
      outcomes.
AB  - PURPOSE OF REVIEW: To review recent research in racial/ethnic disparities in
      breast and gynecologic cancers, focusing on disparities occurring postdiagnosis.
      RECENT FINDINGS: Mortality statistics show that of the cancers under study,
      breast cancer has the greatest impact, and of racial/ethnic groups, African
      Americans suffer the greatest disparities, with highest mortality rates for
      breast, uterine and cervical cancers, and second highest for ovarian cancer.
      Recent studies demonstrated that black breast cancer patients suffer more
      underuse of appropriate adjuvant therapy, and greater delays in diagnosis and
      institution of treatments, and blacks and Hispanics suffered greater postsurgical
      pain and symptomatology. Data indicate that the biology of some breast cancers in
      blacks is unique and more aggressive. One study demonstrated that more black
      breast cancer patients died of nonbreast cancer causes and that excessive
      comorbidity in blacks explained substantial amounts of survival disparity.
      Research is beginning to identify important disparities in nonblack minority
      racial/ethnic groups, including Hispanics and South Asian Americans. SUMMARY:
      Research is continuing to identify and explain an important group of disparities 
      African American disparities in breast cancer outcomes. Disparities in other
      minority racial/ethnic groups, and in ovarian, uterine and cervical cancers, are
      at an emerging stage. Continuing efforts at all fronts are needed.

PMID- 17218850
TI  - Positron emission tomography imaging for gynecologic malignancy.
AB  - PURPOSE OF REVIEW: The utility of positron emission tomography (PET) in
      gynecologic malignancy has increased rapidly in recent years. This review
      examines publications in this area. RECENT FINDINGS: PET scans are mostly
      performed using 18-fluorodeoxyglucose (FDG-PET). It is valuable in primary
      staging of untreated advanced cervical cancer, for posttreatment unexplained
      tumor marker elevation and restaging of potentially curable recurrent cervical
      cancer. Its value in early-stage cervical cancer is limited. In ovarian cancer,
      sequential imaging predicts response to neoadjuvant chemotherapy and survival. It
      also provides benefits when increases in serum CA 125 or computed
      tomography/magnetic resonance imaging defined recurrence is noted but biopsy
      deemed infeasible. A few studies have shown that FDG-PET may facilitate optimal
      management of endometrial cancer, especially for posttherapy surveillance and
      after salvage therapy. FDG-PET is potentially useful in selected gestational
      trophoblastic neoplasia by monitoring response and localizing viable tumors after
      chemotherapy. Scanty studies have been reported in vulvar and vaginal cancer. The
      methodology and prospects of using integrated PET/computed tomography in the
      management of gynecological cancer are discussed. Other PET compounds are briefly
      introduced. SUMMARY: The role of PET or PET/computed tomography has evolved from
      a diagnostic tool into a potential indicator of response to treatment and
      prognosis. Evaluating this tool by clinical impact is an attractive end point.

PMID- 17218851
TI  - Chemotherapy for high-risk early-stage endometrial cancer.
AB  - PURPOSE OF REVIEW: To discuss the usefulness of chemotherapy in high-risk early
      stage endometrial cancer and the best chemotherapy regimen. RECENT FINDINGS:
      External radiation therapy has been successfully used to prevent local
      recurrence; however, it does not improve the overall survival and it increases
      the incidence of late toxicity. A recent randomized study revealed that adjuvant
      platinum-based combination chemotherapy might be a suitable alternative to
      radiotherapy for high-risk early-stage endometrial cancer. The optimal regimen is
      still in question because combinations of doxorubicin-cisplatin and paclitaxel
      doxorubicin-cisplatin cause significant toxicity. The combination of paclitaxel
      carboplatin may be better than doxorubicin-cisplatin with regard to toxicities.
      SUMMARY: Radiation treatment following surgery has been the standard adjuvant
      therapy for endometrial cancer for a long time. Radiotherapy decreases the local
      recurrence rates; however, a significant impact on the overall survival has not
      been demonstrated. The usefulness of adjuvant chemotherapy has been demonstrated
      by only a little evidence. Nonetheless, we are encouraged by a recent randomized
      study. In light of the excellent outcomes associated with early-stage endometrial
      cancer, it is important to conduct another large randomized trial based on
      standardization of high-risk criteria to evaluate the efficacy of adjuvant
      chemotherapy.

PMID- 17218852
TI  - Fine needle aspiration for evaluation of breast masses.
AB  - PURPOSE OF REVIEW: Fine needle aspiration has been used for many years as a
      diagnostic tool for breast lesions, with high sensitivity and specificity. There
      is controversy as to whether this technique should be replaced by other
      diagnostic procedures such as core biopsy. This review aims to re-evaluate the
      usefulness of breast fine needle aspiration. RECENT FINDINGS: During the past 10
      years many institutions have replaced fine needle aspiration by core biopsy and
      related techniques such as vacuum-assisted core biopsy and advanced breast biopsy
      instrument action. Other institutions continue to use fine needle aspiration as a
      first line of investigation for breast lesions. This technique is especially
      useful in radiologically benign lesions and when combined with image guidance.
      The use of the 'triple test' (combined cytologic, clinical and radiologic
      findings) decreases false-negative and false-positive results. SUMMARY: Fine
      needle aspiration continues to be an acceptable and reliable procedure for the
      preoperative diagnosis of breast lesions, particularly in developing countries,
      and when used as part of the 'triple test'. Accurate diagnosis requires
      experience in both aspiration technique and specimen interpretation. Clinicians
      should be mindful of the limitations of the technique. The choice between fine
      needle aspiration and core biopsy should be individualized for the patient.

PMID- 17218853
TI  - HER2/neu role in breast cancer: from a prognostic foe to a predictive friend.
AB  - PURPOSE OF REVIEW: The principal effort of this review was to elucidate the role
      of human epidermal growth factor receptor 2/neu expression in breast cancer,
      either as an independent prognostic factor or a predictive marker of response to
      antineoplastic therapy, in light of the most recent results obtained with the use
      of trastuzumab, in either the metastatic or the adjuvant setting. RECENT
      FINDINGS: Human epidermal growth factor receptor 2-overexpressing breast cancer
      is known to be associated with particularly aggressive disease and poor
      prognosis. On the other hand, human epidermal growth factor receptor 2/neu
      overexpression may predict response to endocrine therapy or chemotherapy.
      Nevertheless, trastuzumab increases the clinical benefit of first-line
      chemotherapy in patients with metastatic breast cancers that overexpress human
      epidermal growth factor receptor 2. Decades of randomized clinical trials on the
      front-line treatment of metastatic breast cancer have never been able to show so
      remarkable differences in survival as recent randomized trials comparing
      chemotherapy with chemotherapy plus trastuzumab in women with human epidermal
      growth factor receptor 2-overexpressing metastatic breast cancer have been able
      to do. SUMMARY: In the pretrastuzumab era, retrospective analyses have shown that
      human epidermal growth factor receptor 2 overexpression is an adverse prognostic
      factor associated with an increased risk of disease recurrence and death. In the
      trastuzumab era, this drug has changed the natural history of human epidermal
      growth factor receptor 2-positive breast cancer, either in the metastatic or,
      according to the most recent evidences, in the adjuvant setting.

PMID- 17218854
TI  - Ductal carcinoma in situ: a review of recent advances.
AB  - PURPOSE OF REVIEW: This review summarizes recent findings on ductal carcinoma in
      situ of the breast and their impact on prognosis and management of the disease.
      RECENT FINDINGS: Great advances have been made in our understanding of ductal
      carcinoma in situ. Nuclear grading is probably the most important pathological
      factor that affects clinical outcome and correlates with distinct genetic
      pathways. Identifying key molecules in each pathway may provide better markers
      for prognostic, predictive and therapeutic purposes. Not all cases of ductal
      carcinoma in situ will progress to invasive ductal carcinoma, and identifying
      this subgroup of patients should lead to a reduction of overtreatment. Progenitor
      cell theory at the cellular level and sick lobe theory at the architectural level
      may help provide a better understanding of ductal carcinoma in situ from a
      different perspective and facilitate the development of individualized therapy.
      Prevention of local recurrence is the primary goal for treatment. Debate
      continues, however, on the use of radiotherapy, hormonal therapy, and sentinel
      lymph node biopsy. A panel of molecular markers may be needed for accurately
      predicting clinical outcome for the disease. SUMMARY: Understanding the
      carcinogenesis of ductal carcinoma in situ at the molecular level may lead to an
      optimal individualized therapy with minimal over or undertreatment.

PMID- 17218855
TI  - New agents in development for breast cancer.
AB  - PURPOSE OF REVIEW: This review summarizes the continuing value of some
      therapeutic drugs and new agents under development for the treatment of breast
      cancer. RECENT FINDINGS: Overexpression and activation of various growth factor
      receptors occurs frequently in human breast cancer. Therapeutic approaches mainly
      involve the epidermal growth factor receptor family, insulin-like growth factor
      receptor and vascular endothelial growth factor receptor. Therapeutic agents
      targeting these receptors include the monoclonal antibodies trastuzumab and
      pertuzumab, and the small-molecule inhibitors gefitinib and erlotinib. Other
      small-molecule and dual inhibitors are in development, some of which have been
      demonstrated to have higher efficacy in the treatment of breast cancer. The
      selective estrogen receptor modulators and aromatase inhibitors continue to be
      valuable in the endocrine therapy of breast cancer. These drugs have been shown
      to have higher efficacy than conventional therapy agents, and to have extensive
      potential, especially in the treatment of postmenopausal women with advanced
      breast cancer. SUMMARY: Approved agents including epidermal growth factor
      receptor-targeted inhibitor, selective estrogen receptor modulators and aromatase
      inhibitors continue to be valuable in treating breast cancer. To overcome the
      acquired resistance caused by these agents and to enhance the therapy effect, the
      development of new and specific dual inhibitors targeting various growth factor
      receptors will be important in the future.

PMID- 17218856
TI  - Dose-dense chemotherapy for primary breast cancer.
AB  - PURPOSE OF REVIEW: Dose density is a relative term referring to the
      administration frequency of chemotherapy drugs and regimens compared with
      standard regimens. The concept of dose-dense chemotherapy is based on the
      hypothesis that maximal chemotherapy effectiveness can be achieved by scheduling
      the interval of chemotherapy to correspond to the period of most rapid tumor
      growth. The present paper aims to outline the theoretical framework for dose
      dense chemotherapy and to review recent clinical trials addressing this concept
      within adjuvant breast cancer treatment. RECENT FINDINGS: Several randomized
      trials have been conducted to test the feasibility and effectiveness of
      anthracycline and/or taxanes-based dose-dense strategies. They demonstrate that
      using hematopoietic growth factor support has made dose-dense therapy safe and
      feasible. Dose-dense strategies have been associated with a modest impact on
      disease recurrence and overall survival of patients with early-stage breast
      cancer. Subset analyses suggest increased benefits for specific tumor subtypes
      such as hormone receptor-negative, highly proliferative or HER2 overexpressing
      tumors. SUMMARY: Trials in unselected patients with early-stage breast cancer
      have demonstrated promising results for dose-dense chemotherapy. Further studies
      are needed to define the optimal regimen and the patient population that will
      receive the greatest benefit from this therapy.

PMID- 17218857
TI  - Bibliography. Current world literature. Gynecologic cancer.

PMID- 17218861
TI  - How to give medicine to children.

PMID- 17218862
TI  - Old man winter gets an icy grip on the heartland: emergency preparedness and
      management on the plains.

PMID- 17218863
TI  - Infection control matters in home healthcare: Mumps update.
AB  - Infection control is pivotal to good nursing care. This column is dedicated to
      new developments in infection control that affect home healthcare nursing. In
      this issue, we examine the outbreak of mumps that began in the Midwestern states
      resulting in new mumps immunization guidelines for all healthcare providers.

PMID- 17218865
TI  - Pediatric assessment: The little differences.

PMID- 17218866
TI  - The innovative use of Six Sigma in home care.
AB  - The Prospective Payment System had significant impact on home healthcare agencies
      throughout the nation. Virtua Home Care, located in Southern New Jersey, realized
      the need for process improvement in order to remain viable. Six Sigma was
      introduced to the agency and the Define, Measure, Analyze, Improve, and Control
      processes were initiated to achieve sustainable results, and within 9 months,
      Virtua Home Care improved regulatory compliance, experienced a deficiency-free
      survey, and recognized a 1.2 million dollars financial gain.

PMID- 17218867
TI  - Home health admission and care of a pediatric ventilator-dependent client.

PMID- 17218868
TI  - End-of-life care for infants.
AB  - Carey, diagnosed with Trisomy 13, was 4 months old when he died. The moment of
      his death was really quite beautiful. He looked so peaceful resting in his
      mother's arms. She kissed him softly and said her good-byes. Tears stained her
      cheeks as Carey's father gently put his arms around both of them. They relaxed as
      he took his last breath, confident that they had done their best in caring for
      him. They had given Carey the best 4 months he could have. They will always
      remember him. After a few moments alone with Carey, they handed him to the
      hospice nurse. She and the social worker took care of the last-minute
      arrangements while the extended family members consoled one another. That night,
      the family began a new phase of their journey, carrying the memories of Carey and
      his life with them forever.

PMID- 17218869
TI  - Improving care in the home for children with palliative care needs.

PMID- 17218873
TI  - Influenza vaccination of home care and hospice staff as a component of a patient
      safety program.

PMID- 17218872
TI  - Prevent medication errors: A New Year's resolution: Teaching patients about their
      medications.

PMID- 17218876
TI  - Exercise capacity of cardiac asymptomatic hereditary hemochromatosis subjects.
AB  - PURPOSE: The exercise capacity of cardiac asymptomatic subjects with hereditary
      hemochromatosis (HH) has not been well described. In this study, we tested
      whether the iron overload associated with HH affected exercise capacity with a
      case control study design. METHODS: Forty-three HH and 21 normal control subjects
      who were New York Heart Association functional class I underwent metabolic stress
      testing using the Bruce protocol at the clinical center of the National
      Institutes of Health. Exercise capacity was assessed with minute ventilation
      (.VE), oxygen uptake (.VO2), and carbon dioxide production (.VCO2) using a breath
      by-breath respiratory gas analyzer. RESULTS: The exercise capacity of HH subjects
      was not statistically different from that of control subjects (exercise time 564
      +/- 135 vs 673 +/- 175 s, P = 0.191; peak .VO2 29.6 +/- 6.4 vs 32.5 +/- 6.7
      mL.kg(-1).min(-1), P = 0.109; ventilatory threshold 19.0 +/- 3.4 vs 21.0 +/- 5.0
      mL.min(-1).kg(-1), P = 0.099; data are for HH vs control subjects). Ventilatory
      efficiency was comparable between groups (.VE/.VCO2 slope 23.7 +/- 3.2 vs 23.4 +/
      4.2, P = 0.791). No significant correlation between the markers of iron levels
      and the markers of exercise capacity was noted. Iron depletion by 6-month
      phlebotomy therapy in 18 subjects who were newly diagnosed did not affect
      exercise testing variables (exercise time 562 +/- 119 vs 579 +/- 118 s, P =
      0.691; peak .VO2 29.5 +/- 3.7 vs 29.1 +/- 4.7 mL.kg(-1).min(-1), P = 0.600;
      ventilatory threshold 18.5 +/- 2.8 vs 17.9 +/- 3.8 mL.kg(-1).min(-1), P = 0.651;
      data are from before and after phlebotomy therapy). Abnormal ischemic
      electrocardiographic responses and complex arrhythmias were more frequently seen
      in HH subjects. CONCLUSIONS: The aerobic exercise capacity of asymptomatic HH
      subjects seems not to be statistically different from that of normal subjects.
      The iron levels do not seem to affect exercise capacity in asymptomatic HH
      subjects.

PMID- 17218877
TI  - An ultracyclist with pulmonary edema during the Bicycle Race Across America.
AB  - Ultraendurance athletic events tax the limits of physiological homeostasis.
      Maintenance of sodium and water balance is a particularly difficult challenge in
      such events. We present the case of a 38-yr-old participant in the Bicycle Race
      Across America who developed severe pulmonary edema while cycling at an altitude
      of 2380 m on the fourth day of the race. With hospitalization and standard
      support for pulmonary edema, he made a quick, full recovery. A post-race work-up
      revealed no evidence of underlying cardiopulmonary disease or susceptibility to
      high-altitude pulmonary edema. His weight on the day of hospitalization was 2.7
      kg greater than his pre-race weight. We hypothesize that his excessive daily
      sodium intake (23-25 g, or 1000-1100 mEq) during the course of the race likely
      led to an expanded extracellular volume, increased hydrostatic pressure, and
      decreased oncotic pressure. These factors, in combination with ambient hypoxia,
      elevated cardiac output, and reduced renal perfusion expected with sustained,
      high-level exercise, may have led to the development of acute pulmonary edema.
      This case highlights the pitfalls of overly aggressive sodium intake in endurance
      races, particularly when such races are conducted at high altitude, where the
      hypoxia-induced rise in pulmonary artery pressures may amplify the effects of
      changes in hydrostatic and oncotic pressure that occur with extracellular volume
      expansion.

PMID- 17218878
TI  - Effects of an intrahospital exercise program intervention for children with
      leukemia.
AB  - PURPOSE: The purpose was to investigate the effect of a 16-wk intrahospital
      supervised conditioning program including both resistance and aerobic training
      and a 20-wk detraining period on measures of aerobic fitness, muscular strength,
      functional mobility, ankle range of motion, and quality of life (QOL) in children
      receiving treatment for acute lymphoblastic leukemia (ALL). METHODS: Seven
      children (four boys, three girls; age: 5.1 +/- 1.2 yr, body mass: 24.0 +/- 5.8
      kg, height: 114.6 +/- 7.7 cm) in the maintenance phase of treatment against ALL
      performed three sessions per week for 16 wk of resistance (one set of 8-15
      repetitions of 11 exercises) and aerobic training (30 min at > 70% HRmax)
      followed by 20 wk of detraining where no structured exercise program was
      performed. Before training, after training, and after detraining, a treadmill
      test determining .VO2peak and ventilator threshold (VT), muscular strength (6RM),
      functional mobility (timed up and down stairs test, time up and go 3-m and 10-m
      tests), passive and dynamic ankle range of motion, and self-reported quality of
      living were determined. RESULTS: After training, significant increases in
      .VO2peak, VT, upper- and lower-body muscular strength, and all measures of
      functional mobility were shown (P < 0.05). Muscular strength was well maintained
      (significantly greater than before training and no significant decrease from
      after training) during detraining, whereas .VO2peak, VT, and functional mobility
      (not significantly different from before training but no significant decrease
      from after training) were only partially retained. CONCLUSION: Young children in
      the maintenance phase of treatment against ALL can safely perform both aerobic
      and resistance training. Training results in significant increases in measures of
      aerobic fitness, strength, and functional mobility. During detraining, strength
      and functional mobility are well maintained, whereas .VO2peak and VT are
      partially maintained.

PMID- 17218879
TI  - Prevalence of musculoskeletal disorders at the NFL Combine--trends from 1987 to
      2000.
AB  - PURPOSE: The National Football League holds an annual combine where individual
      teams evaluate college football players likely to be drafted. As part of the
      combine, the players are evaluated with a medical history, physical exam, and
      review of imaging studies, and then they are rated medically as to their ability
      to participate in the NFL. The purpose of this study was to review the prevalence
      of musculoskeletal disorders in this population and to test the hypothesis that
      fewer players were medically disqualified over calendar time from 1987 to 2000.
      METHODS: The available summary data for all players reviewed at the annual
      combine by the medical staff of one NFL team from 1987 to 2000 was analyzed,
      including each player's position, collegiate division, medical rating, and their
      diagnoses and surgical procedures. RESULTS: A total of 5047 complete records were
      available for analysis. The average number of diagnoses per player was 2.45, and
      the average number of procedures was 0.53. The most common diagnoses were ankle
      sprain, burner, hand/wrist soft-tissue injury, knee MCL injury, and AC-joint
      injury. The most common procedures were meniscectomy, knee arthroscopy, ACL
      reconstruction, shoulder stabilization, and ORIF ankle fracture. Overall, 5.63%
      of the players were rejected for medical reasons. The risk of failure dropped
      during the study period (P < 0.0002). Over time, fewer players with a history of
      ACL reconstruction received a failing grade (P = 0.0005). CONCLUSION: The
      percentage of athletes with a failing grade, particularly those with a history of
      ACL reconstruction, decreased over the study period. Knowing the trends in
      prevalence of injury and treatment for these athletes may help optimize their
      care and aid the development of injury-prevention and treatment strategies.

PMID- 17218880
TI  - Pars interarticularis stress lesions in the lumbar spine of cricket fast bowlers.
AB  - PURPOSE: This prospective magnetic resonance (MR) imaging study investigated the
      development of symptomatic pars lesions in the lumbar spine of adolescent cricket
      fast bowlers. METHODS: Annual MR examinations of the lumbar spine in male fast
      bowlers (N = 51) and swimmers (N = 20) without a prestudy history of symptomatic
      back injury were conducted to identify stress-induced pars injuries over 4 and 2
      yr periods, respectively. RESULTS: Symptomatic L4 and L5 pars lesions developed
      in 11 of 51 and 1 of 51 of the bowlers, respectively. Preexisting L5 lesions were
      observed in both bowlers (10 of 51) and swimmers (4 of 20). No significant
      difference existed between the proportion of bowlers and swimmers with
      preexisting L5 lesions (P = 1.00, Fisher's exact test). In contrast, bowlers had
      a significantly greater proportion of L4 pars lesions compared with swimmers,
      with 22% of the bowlers developing L4 injuries during the study, whereas there
      were no L4 lesions in the swimmers (P = 0.027, Fisher's exact test). The
      symptomatic L4 lesions in the bowlers developed between 15 and 17 yr of age, and
      all were unilateral lesions lateralized to the nonbowling-arm side. The MR
      characteristics of the L4 pars lesions were consistent with a stress fracture
      through the cortical bone. Of the acquired L4 lesions in the bowlers, 4 of 11 and
      7 of 11 developed in individuals with and without preexisting L5 defects,
      respectively. No significant association existed between the acquired L4 pars
      lesions and preexisting L5 defects in the bowlers (P = 0.216, Fisher's exact
      test). CONCLUSION: Fast bowling was directly associated with the development of
      symptomatic pars lesions of the lumbar spine, particularly unilateral L4 stress
      lesions, in a significant proportion of the adolescent bowlers examined in this
      prospective MR study.

PMID- 17218881
TI  - Therapist education impacts the massage effect on postrace muscle recovery.
AB  - PURPOSE: The intention of this study was to assess the effectiveness of massage
      on muscle recovery as a function of therapist education in participants who
      completed a 10-km running race. METHODS: Race participants were offered a 12- to
      15-min massage immediately post-event. Participants were randomly assigned to a
      student therapist with either 450, 700, or 950 h of didactic training in massage.
      Muscle soreness was recorded by questionnaire using a 0- to 10-point visual scale
      at time points immediately before and after massage, and 24 and 48 h post-event.
      Eight hundred ninety-five subjects were recruited, with 317 subjects returning
      questionnaires from all time points. RESULTS: Race participants who received
      massage from student therapists with 950 h of didactic training reported
      significantly greater improvement in muscle soreness across time compared with
      those who received massage from therapists with 700 or 450 h of education in
      massage (P < 0.01). On study entry, there was no difference in muscle soreness (P
      = 0.99), with a group mean of 4.4 +/- 0.4; at the 24-h measurement, soreness was
      2.4 +/- 0.6, 3.7 +/- 0.5, and 3.6 +/- 0.9 for the 950-, 700-, and 450-h groups,
      respectively (P < 0.01). CONCLUSION: Level of therapist training was shown to
      impact effectiveness of massage as a post-race recovery tool; greater reduction
      in muscle soreness was achieved by therapists with 950 h of training as opposed
      to those with 700 or 450 h.

PMID- 17218882
TI  - Musculoskeletal fitness and weight gain in Canada.
AB  - BACKGROUND: Obesity is a growing health issue in Canada, and identifying the
      determinants of weight gain is important for the development of appropriate
      prevention strategies. PURPOSE: To quantify the association between
      musculoskeletal fitness (MSF) and subsequent weight gain and development of
      obesity. METHODS: The sample included 606 participants (20-69 yr; 291 men, 315
      women) from the Physical Activity Longitudinal Study (PALS), a follow-up of
      participants from the 1981 Canadian Fitness Survey. Standardized assessments of
      height, weight, MSF (push-ups, sit-ups, grip strength, and trunk flexibility),
      and cardiorespiratory fitness were made at baseline (1981). Follow-up data on
      self-reported height and weight and body mass index (BMI) were collected by
      survey in 2002-2004. Logistic regression was used to predict obesity and weight
      gain of > or = 10 kg between 1981 and 2002-2004. RESULTS: During the 20-yr follow
      up, the prevalence of obesity (BMI > or = 30 kg.m(-2)) increased from 3.1 to
      15.2%, reflecting a mean weight gain of 7.4 kg (men: 6.7 kg; women: 8.1 kg).
      Further, independent of age, sex, baseline BMI, physical activity,
      cardiorespiratory fitness, smoking, alcohol consumption, and income, low MSF was
      associated with significantly higher odds of having gained at least 10 kg during
      follow-up (OR: 1.78, 95% CI: 1.14-2.79). CONCLUSIONS: The results indicate that
      MSF is a significant predictor of weight gain during a 20-yr period. Promoting
      participation in activities that enhance MSF may be beneficial in attenuating age
      related weight gain and in preventing obesity among Canadians.

PMID- 17218883
TI  - Race/ethnicity, social class, and leisure-time physical inactivity.
AB  - PURPOSE: The aims of this study were to determine 1) prevalence of leisure-time
      physical inactivity in a nationally representative sample of non-Hispanic white,
      non-Hispanic black, and Hispanic men and women; 2) prevalence of leisure-time
      inactivity by racial/ethnic group across social class indicators; and 3) the
      relationship between leisure-time inactivity and occupational physical activity,
      independent of other social class indicators. METHODS: The National Physical
      Activity and Weight Loss Survey was a telephone survey of noninstitutionalized
      U.S. adults (4695 men, 6516 women) conducted by random digit dialing between
      September and December 2002. Self-reported physical activity was assessed using
      questions from the 2001 Behavioral Risk Factor Surveillance System. Respondents
      who reported no moderate- or vigorous-intensity physical activity during leisure
      time in a usual week were classified as inactive. Indicators of social class were
      education, family income, employment status, and marital status. RESULTS: Age
      adjusted prevalence of leisure-time inactivity was 9.9% +/- 0.6 SE (standard
      error) and 12.0 +/- 0.6 for white men and women, respectively; 19.0 +/- 2.5 and
      25.2 +/- 2.1 for non-Hispanic black men and women, and 20.9 +/- 2.1 and 27.3 +/-
      2.5 for Hispanic men and women. Within each racial/ethnic group, prevalence of
      leisure-time inactivity was highest among participants of lower social class.
      Differences in inactivity by racial/ethnic group were less evident after
      adjustment for social class. Odds of inactivity were similar across quartiles of
      occupational physical activity after adjustment for age, sex, and social class.
      CONCLUSIONS: Non-Hispanic blacks and Hispanics were more inactive during their
      leisure time than were non-Hispanic whites. Social class but not occupational
      physical activity seems to moderate the relationship between race/ethnicity and
      leisure-time physical inactivity.

PMID- 17218884
TI  - Discrepancies between methods of identifying objectively determined physical
      activity.
AB  - Current methods for validating physical activity (PA) questionnaires typically
      use accelerometers as objective measures for comparison with questionnaire
      responses and obtain low correlations or agreement. PURPOSE: We examined possible
      reasons for weak associations in validation studies by comparing published
      ActiGraph accelerometer intensity cut points with cut points based on intensity
      thresholds for heart rate response to PA. METHODS: Twelve adults (five men, seven
      women; age 31.0 +/- 14.3 yr) wore an ActiGraph accelerometer and a Polar Vantage
      NV heart watch simultaneously for seven consecutive days during their waking
      hours. We identified PA bouts from the minute-by-minute ActiGraph data using
      published accelerometer thresholds for defining moderate- and vigorous-intensity
      PA. We then compared PA bout intensities identified with these criteria with
      intensity classifications of the PA bouts using mean percent heart rate reserve
      (HRR). RESULTS: Most of the moderate-intensity PA bouts identified by the
      Freedson (78.3%), Swartz (88.0%), and Hendelman (94.7%) ActiGraph cut points were
      associated with a mean %HRR < 45% (very light and light intensities). The
      estimated mean frequency with which study participants engaged in moderate
      intensity PA varied with the cut points and type of bouts used and ranged from
      1.1 d.wk(-1) (45-60%HRR) to 7.0 d.wk(-1) (Hendelman cut points). The mean total
      duration on active days ranged from 17.9 min.d(-1)(45-60%HRR) to 139.2 min.d(-1)
      (Hendelman cut points). Fewer bouts of vigorous PA were found in the
      accelerometer data, and most were in the vigorous-intensity category of > or =
      60%HRR. CONCLUSIONS: The method used for analyzing ActiGraph activity data can
      result in large differences in the summary measure of minutes of moderate- to
      vigorous-intensity activity.

PMID- 17218885
TI  - Factorial and construct validity of the athletic identity questionnaire for
      adolescents.
AB  - PURPOSE: This research describes the development of a measure of the general
      attribute of "athletic" in adolescents, encompassing exercise, sport, and
      physical activity. Based on a theoretical model supported in adults, the 40-item
      Athletic Identity Questionnaire (AIQ) for adolescents assesses four dimensions:
      appearance, competence, importance of activity, and encouragement from three
      sources: parents, friends, and teachers/other adults. METHODS: Structural
      equation modeling was used to evaluate the hypothesized four-factor model in a
      development sample of 408 adolescents in eighth grade (mean age 13.4 yr). A
      separate sample (N = 1586) was used to cross-validate the final model. Construct
      validity was examined by testing the model's relationship to self-reported
      (Modifiable Activity Questionnaire-Adolescent, Previous Day Physical Activity
      Recall, Youth Risk Behavior Survey) and objectively measured physical activity
      (MTI accelerometer in sample 3, N = 100). RESULTS: Confirmatory factor analysis
      supported the four-factor structure, and there was also support for a higher
      order model. LISREL correlations between the AIQ factors and self-reported
      physical activity ranged from 0.32 to 0.61, TV watching from -0.20 to -0.50, and
      sport-team participation from 0.20 to 0.54. Pearson correlations between the AIQ
      factors and MTI vigorous physical activity ranged from 0.09 to 0.26 and MTI
      moderate from -0.06 to 0.22. CONCLUSIONS: Findings support the factorial and
      construct validity of the AIQ for adolescents.

PMID- 17218886
TI  - Effect of running training on DMH-induced aberrant crypt foci in rat colon.
AB  - PURPOSE: We examined the effects of treadmill-running training on the induction
      of aberrant crypt foci (ACF), which is the first step of colon cancer induction,
      in the colonic mucosa of rats injected with 1,2-dimethylhydrazine (DMH). METHODS:
      Four-week-old F344 rats (N = 38) were randomly assigned to training (19 rats) and
      control (19 rats) groups. After a week, all rats were given DMH (20 mg.kg(-1)
      body weight) once a week for 2 wk. Running training was started at age 7 wk
      (speed: 10 m.min(-1), 0% grade, 120 min.d(-1), 5 d.wk(-1)). After 4 wk of
      training, the rats were sacrificed and the colon was removed, opened, and counted
      for ACF with 0.2% methylene blue staining. RESULTS: Running training resulted in
      lower body- (P < 0.01) and adipose fat weight (P < 0.05). The numbers of ACF and
      total AC were significantly lower in the running training group than in the
      control group (P < 0.05). The occurrences of one, three, and five aberrant crypts
      per focus were also significantly lower in the running training group than in the
      control group (P < 0.05). The ratios of total AC/ACF did not significantly differ
      between the running training and control groups. CONCLUSIONS: The results of the
      present investigation suggest that low-intensity running training inhibits the
      DMH-induced initiation of colon ACF development.

PMID- 17218887
TI  - Early adaptations to training: upregulation of alpha-myosin heavy chain gene
      expression.
AB  - Chronic exercise induces adaptations that increase the functional capacity of the
      cardiovascular system. Aside from ventricular growth, these adaptations include a
      shift in the MHC isoenzyme pattern to enhance ventricular contractility. It is
      unclear whether adaptations by the contractile elements are an early event and
      specific to exercise, or whether they progress as a function of cardiac growth.
      Examining early adaptations to training is also important because it is during
      this period when the greatest imbalance between increased demand and functional
      capacity exists, and it is likely that the mechanisms responsible for propagating
      changes in the myocardial phenotype are most active. PURPOSE: To determine
      whether changes in left ventricular (LV) contractile elements are an early
      adaptation to chronic exercise. METHODS: Rats were randomly assigned to sedentary
      control or exercise training groups for 1 or 10 wk of training. After training,
      the LV was analyzed for protein by Western blot or mRNA by Northern and real-time
      QRT-PCR analysis. RESULTS: Plantaris cytochrome oxidase activity was
      significantly (P < 0.05) increased by 1 wk (+28%) or 10 wk (+32%) of training.
      Training significantly increased LV myofibrillar alpha-MHC protein and alpha-MHC
      mRNA after both training periods. No changes in myofibrillar beta-MHC protein or
      beta-MHC-mRNA were observed. After 1 wk of training, LV skeletal alpha-actin-mRNA
      was significantly increased, whereas no changes were found for ANF,
      glyceraldehyde dehydrogenase, or cytochrome oxidase IV. Gel mobility shift
      analysis determined that YY1 DNA binding was significantly decreased in LV
      extracts from trained animals, although no change in YY1-mRNA expression was
      observed. CONCLUSIONS: Increased myofibrillar alpha-MHC protein and alpha-MHC
      mRNA expression are early events in the adaptation to chronic exercise and occur
      before significant cardiac growth. These adaptations enhance myocardial
      contractility and permit increases in maximal cardiac output during heavy
      exercise.

PMID- 17218888
TI  - Impact of repeated prolonged exercise bouts on cardiac function and biomarkers.
AB  - PURPOSE: The present study examined the impact of repeated bouts of prolonged (<
      60 min) exercise on left ventricular function and cardiac biomarkers. METHODS:
      Ten athletes completed a 15.3-mile hill run on three consecutive days and were
      assessed before, immediately after, 1 h after, and 20 h after each bout. Six of
      the athletes completed a fourth bout. Left ventricular (LV) function was examined
      echocardiographically using two-dimensional M-mode, Doppler, and flow propagation
      velocity (Vp). Venous blood samples were analyzed for cardiac biomarkers
      including cardiac troponin T (cTnT). RESULTS: Ejection fraction (EF)
      significantly decreased (P = 0.027) after the third exercise bout compared with
      baseline (mean +/- SD: 56.3 +/- 4.4 vs 51.3 +/- 5.9%), accompanied by a
      nonsignificant decrease in systolic blood pressure/end systolic volume (SBP/ESV)
      ratio. A sustained depression in systolic function 20 h after bout 3 also
      persisted in the subset who completed a fourth bout, yet this did not reach
      clinical levels. Significant (P < 0.01) reductions in early to late diastolic
      filling (E:A) ratio pre-to post-bout 1 (mean +/- SD: 1.9 +/- 0.5 vs 1.4 +/- 0.3)
      and pre- to post-bout 3(2.0 +/- 0.5 vs 1.3 +/- 0.4) normalized after each 20-h
      recovery period. A similar pattern of change was observed in Vp. Cardiac troponin
      T was elevated in four individuals 1 h after bout 1 (range: 0.013-0.125 microg.L(
      1)) but was undetectable thereafter except in one athlete. CONCLUSION: Repeated
      bouts of prolonged exercise induce short-term reductions in diastolic filling and
      a cumulative decrease in systolic function, yet these alterations seem to have
      minimal clinical or functional impact. Elevated cTnT after the initial bout, but
      not thereafter, may represent an adaptive response to prolonged exercise.

PMID- 17218889
TI  - Related trends in locomotor and respiratory muscle oxygenation during exercise.
AB  - PURPOSE: We investigated the potential effect of respiratory muscle work on leg
      muscle oxygenation without artificial intervention in non-endurance-trained young
      subjects and searched for the range of intensity when this effect could occur.
      METHODS: We simultaneously monitored accessory respiratory and leg muscle
      oxygenation patterns with near-infrared spectroscopy (NIRS) in 15 healthy young
      men performing maximal incremental exercise on a cycle ergometer. Pulmonary gas
      exchange was measured. The respiratory compensation point (RCP) was determined.
      Oxygenation (RMO2) and blood volume (RMBV) of the serratus anterior (accessory
      respiratory muscle) and of the vastus lateralis (LegO2 and LegBV) were monitored
      with NIRS. The breakdown point of accessory respiratory muscle oxygenation
      (BPRMO2) and the accelerated (BP1LegO2) and attenuated fall (BP2LegO2) in leg
      muscle oxygenation were detected. RESULTS: BPRMO2 occurred at approximately 85%
      .VO2max and was related to RCP (r = 0.88, P < 0.001). BP2LegO2 appeared at
      approximately 83% .VO2max and was related to RCP (r = 0.57, P < 0.05) and with
      BPRMO2 (r = 0.64, P = 0.01). From BP2LegO2 to maximal exercise, LegBV was
      significantly reduced (P < 0.05). CONCLUSION: In active subjects exercising at
      heavy exercise intensities, we observed that the appearance of the accelerated
      drop in accessory respiratory muscle oxygenation-associated with high ventilatory
      level-was related with the attenuated fall in leg muscle oxygenation detected
      with near-infrared spectroscopy. This suggests that the high oxygen requirement
      of respiratory muscle leads to limited oxygen use by locomotor muscles as
      demonstrated in endurance-trained subjects. The phenomenon observed was
      associated with reduced leg blood volume, supporting the occurrence of leg
      vasoconstriction. These events appeared not only at maximal exercise but onward
      above the respiratory compensation point.

PMID- 17218890
TI  - .VO2max and the plateau--needed or not?

PMID- 17218891
TI  - Maximal oxygen uptake as a parametric measure of cardiorespiratory capacity.
AB  - INTRODUCTION: Maximal oxygen uptake (.VO2max) was defined by Hill and Lupton in
      1923 as the oxygen uptake attained during maximal exercise intensity that could
      not be increased despite further increases in exercise workload, thereby defining
      the limits of the cardiorespiratory system. This concept has recently been
      disputed because of the lack of published data reporting an unequivocal plateau
      in .VO2 during incremental exercise. PURPOSE: The purpose of this investigation
      was to test the hypothesis that there is no significant difference between the
      .VO2max obtained during incremental exercise and a subsequent supramaximal
      exercise test in competitive middle-distance runners. We sought to determine
      conclusively whether .VO2 attains a maximal value that subsequently plateaus or
      decreases with further increases in exercise intensity. METHODS: Fifty-two
      subjects (36 men, 16 women) performed three series of incremental exercise tests
      while measuring .VO2 using the Douglas bag method. On the day after each
      incremental test, the subjects returned for a supramaximal test, during which
      they ran at 8% grade with the speed chosen individually to exhaust the subject
      between 2 and 4 min. .VO2 at supramaximal exercise intensities (30% above
      incremental .VO2max) was measured continuously. RESULTS: .VO2max measured during
      the incremental test (63.3 +/- 6.3 mL.kg(-1).min(-1); mean +/- SD) was
      indistinguishable from the .VO2max during the supramaximal test (62.9 +/- 6.2, N
      = 156; P = 0.77) despite a sufficient duration of exercise to demonstrate a
      plateau in .VO2 during continuous supramaximal exercise. These data provide
      strong support for the hypothesis that there is indeed a peak and subsequent
      plateau in .VO2 during maximal exercise intensity. CONCLUSIONS: .VO2max is a
      valid index measuring the limits of the cardiorespiratory systems' ability to
      transport oxygen from the air to the tissues at a given level of physical
      conditioning and oxygen availability.

PMID- 17218892
TI  - Attenuated growth hormone response to resistance exercise with prior sprint
      exercise.
AB  - PURPOSE: This study examined effects of prior sprint exercise on hormonal
      responses to subsequent resistance exercise with different recovery periods
      between exercise bouts. METHODS: Nine men performed three types of exercise
      regimens: 1) resistance exercise only (R), 2) resistance exercise with prior
      sprint exercise and 60 min of rest (SR60), and 3) resistance exercise with prior
      sprint exercise and 180 min of rest (SR180). Sprint exercises consisted of
      maximal sprint cycling (eight sets of 5-s sprints with 30-s rest periods between
      sets) with prior 10-min warm-up. Resistance exercise consisted of five exercises,
      each with three sets at a 10-repetition maximum with 1-min rest periods. RESULTS:
      Prior sprint exercise significantly increased blood lactate, glycerol,
      epinephrine, norepinephrine, growth hormone (GH), and free testosterone
      concentrations (P < 0.05). Before the resistance exercise, free fatty acids
      concentration was higher in the SR180 trial than in the SR60 and R trials (P <
      0.05), whereas GH concentration was significantly higher in the SR60 trial (P <
      0.01). After the resistance exercise, no significant difference was found in
      responses of pH, epinephrine, norepinephrine, and free testosterone among trials.
      The SR180 trial showed a smaller GH response (peak value: 7.8 +/- 1.6 (SE) ng.mL(
      1)) than in the R trial (12.8 +/- 3.7 ng.mL(-1)), with no significant difference
      between trials. In the SR60 trial, GH response to resistance exercise was
      attenuated (3.3 +/- 1.2 ng.mL(-1), P < 0.01). Maximal strength and power measured
      immediately before the resistance exercise showed no difference among trials.
      CONCLUSION: These results indicate that GH response to resistance exercise was
      attenuated strongly when the exercise was preceded by sprint exercise and a
      shorter (60 min) recovery period.

PMID- 17218893
TI  - Exercise and postprandial plasma triacylglycerol concentrations in healthy
      adolescent boys.
AB  - PURPOSE: Atherosclerosis is initiated in childhood. Therefore, reducing
      postprandial triacylglycerol concentrations ([TAG]), even in young people, could
      potentially slow atherogenic progression. This study investigated whether
      continuous-exercise and intermittent-games activity would reduce postprandial
      [TAG] in adolescent boys. METHODS: Nineteen subjects were randomly assigned to
      either a continuous-exercise group (N = 10) or an intermittent-games group (N =
      9) and underwent two 2-d trials. Trials were performed a minimum of 7 d apart in
      a randomized order, consisting of a rest trial and either a continuous-exercise
      or intermittent-games trial. In the rest trial, subjects took no exercise on day
      1. On day 1 of the exercise trial, subjects completed four blocks (approximately
      15 min each) of uphill treadmill walking or intermittent-games activity with 3
      min of rest between each block. On day 2, subjects came to the laboratory after
      an overnight fast, and finger-prick blood samples were obtained in the fasted
      state. Subjects then consumed a test meal (1.25 g of fat, 1.07 g of carbohydrate,
      0.20 g of protein, and 67 kJ.kg(-1) body mass). Further blood samples were
      collected at 30 and 45 min and at 1, 3, 4, and 6 h postprandially. RESULTS: The
      total area under the plasma [TAG] versus time curve was lower on day 2 after
      exercise than the rest condition in both groups (Student's t-tests for correlated
      means: continuous-exercise group 14%, P = 0.050; intermittent-games group 26%, P
      = 0.002). CONCLUSION: Both continuous-exercise and intermittent-games activity
      reduce [TAG] in healthy adolescent boys when performed the afternoon before
      ingesting a high-fat meal.

PMID- 17218894
TI  - Sodium loading aids fluid balance and reduces physiological strain of trained men
      exercising in the heat.
AB  - PURPOSE: This study was conducted to determine whether preexercise ingestion of a
      highly concentrated sodium beverage would increase plasma volume (PV) and reduce
      the physiological strain of moderately trained males running in the heat.
      METHODS: Eight endurance-trained (.VO2max: 58 mL.kg(-1).min(-1) (SD 5); 36 yr (SD
      11)) runners completed this double-blind, crossover experiment. Runners ingested
      a high-sodium (High Na+: 164 mmol Na+.L(-1)) or low-sodium (Low Na+: 10 mmol
      Na+.L(-1)) beverage (10 mL.kg(-1)) before running to exhaustion at 70% .VO2max in
      warm conditions (32 degrees C, 50% RH, V(a) approximately equal to 1.5 m.s(-1)).
      Beverages (approximately 757 mL) were ingested in seven portions across 60 min
      beginning 105 min before exercise. Trials were separated by 1-3 wk. Heart rate
      and core and skin temperatures were measured throughout exercise. Urine and
      venous blood were sampled before and after drinking and exercise. RESULTS: High
      Na+ increased PV before exercise (4.5% (SD 3.7)), calculated from Hct and [Hb]),
      whereas Low Na+ did not (0.0% (SD 0.5); P = 0.04), and involved greater time to
      exercise termination in the six who stopped because of an ethical end point (core
      temperature 39.5 degrees C: 57.9 min (SD 6) vs 46.4 min (SD 4); P = 0.04) and
      those who were exhausted (96.1 min (SD 22) vs 75.3 min (SD 21); P = 0.03; High
      Na+ vs Low Na+, respectively). At equivalent times before exercise termination,
      High Na+ also resulted in lower core temperature (38.9 vs 39.3 degrees C; P =
      0.00) and perceived exertion (P = 0.01) and a tendency for lower heart rate (164
      vs 174 bpm; P = 0.08). CONCLUSIONS: Preexercise ingestion of a high-sodium
      beverage increased plasma volume before exercise and involved less
      thermoregulatory and perceived strain during exercise and increased exercise
      capacity in warm conditions.

PMID- 17218895
TI  - Dose-response effects of ingested carbohydrate on exercise metabolism in women.
AB  - PURPOSE: The effect of different quantities of carbohydrate (CHO) intake on CHO
      metabolism during prolonged exercise was examined in endurance-trained females.
      METHOD: On four occasions, eight females performed 2 h of cycling at
      approximately 60% .VO2max with ingestion of beverages containing low (LOW, 0.5
      g.min(-1)), moderate (MOD, 1.0 g.min(-1)), or high (HIGH, 1.5 g.min(-1)) amounts
      of CHO, or water only (WAT). Test solutions contained trace amounts of [U-13C]
      glucose. Indirect calorimetry combined with measurement of expired 13CO2 and
      plasma 13C enrichment enabled calculation of exogenous CHO, liver-derived
      glucose, and muscle glycogen oxidation during the last 30 min of exercise.
      RESULTS: The highest rates of exogenous CHO oxidation were observed in MOD, with
      no further increases in HIGH (peak rates of 0.33 +/- 0.02, 0.50 +/- 0.03, and
      0.48 +/- 0.05 g.min(-1) for LOW, MOD, and HIGH, respectively; P < 0.05 for LOW vs
      MOD and HIGH). Endogenous CHO oxidation was lowest in MOD (0.99 +/- 0.06, 0.82 +/
      0.08, 0.70 +/- 0.07, and 0.89 +/- 0.09 g.min(-1); P < 0.05 for MOD vs all other
      trials). Compared with WAT, CHO ingestion reduced liver glucose oxidation during
      exercise by approximately 30% (P < 0.05 for WAT vs all CHO). Differential rates
      of muscle glycogen oxidation were observed with different CHO doses (0.57 +/-
      0.07, 0.53 +/- 0.08, 0.41 +/- 0.07, and 0.60 +/- 0.09 g.min(-1) for WAT, LOW,
      MOD, and HIGH respectively; P < 0.05 for MOD vs HIGH). CONCLUSION: In endurance
      trained women, the highest rates of exogenous CHO oxidation and greatest
      endogenous CHO sparing was observed when CHO was ingested at moderate rates (1.0
      g.min(-1), 60 g.h(-1)) during exercise.

PMID- 17218896
TI  - Mechanical and metabolic responses with exercise and dietary carbohydrate
      manipulation.
AB  - PURPOSE: To investigate the effects of altered muscle glycogen content on the
      mechanical and metabolic responses to prolonged exercise of moderate intensity.
      METHODS: Eight volunteers (.VO2peak = 49.3 +/- 1.2 mL.kg(-1).min(-1)) cycled to
      fatigue on two occasions: after a 3-d low-carbohydrate diet (Lo CHO), which had
      been preceded by glycogen-depleting exercise, and then after a 3-d high
      carbohydrate diet (Hi CHO). Metabolic and mechanical properties were assessed at
      both Lo CHO and Hi CHO before exercise (Pre), at 30 min of exercise (30 min), at
      fatigue in Lo CHO (Post 1), and again at fatigue after a brief rest (Post 2).
      RESULTS: For the Lo CHO cycle, time to fatigue averaged 66.7 +/- 4.5 and 9.5 +/-
      1.7 min for Post 1 and Post 2, respectively. For Hi CHO, Post 2 time to fatigue
      was 64.9 +/- 6.3 min. Muscle glycogen was elevated (P < 0.05) by approximately
      40% in Hi CHO compared with Lo CHO. Phosphocreatine, although higher (P < 0.05)
      by approximately 25% during exercise in Hi CHO, was not different at Pre. Similar
      but reciprocal effects (P < 0.05) were observed for inorganic phosphate and
      creatine. Force at low frequencies of stimulation was maximally reduced (P <
      0.05) by approximately 26-38% by 30 min of exercise, regardless of condition.
      CONCLUSION: A 7-d exercise-dietary protocol leads to both an elevation in muscle
      glycogen and improved energy homeostasis during exercise. Although these
      adaptations may explain the improved cycle performance, they are not related to
      the progression of muscle fatigue as assessed statically at low frequencies of
      stimulation.

PMID- 17218897
TI  - Neuromuscular fatigue profile in endurance-trained and power-trained athletes.
AB  - PURPOSE: This study examined the effects of training background on the
      relationship between the neuromuscular fatigue profile and maximal voluntary
      torque production in isometric, concentric, and eccentric contraction modes.
      METHODS: Before and after three sets of 31 isokinetic concentric knee extensions
      at 60 degrees .s(-1), voluntary and electrically induced contractions were
      recorded in 14 endurance-trained (ENDU) men (seven cyclists: age 25 +/- 2 yr,
      mass 70 +/- 8 kg, height 175 +/- 5 cm; and seven triathletes: age 27 +/- 4 yr,
      mass 71 +/- 5 kg, height 179 +/- 6 cm) and seven explosive power-trained men
      (EXPLO: age 24 +/- 1 yr, mass 73 +/- 5 kg, height 179 +/- 4 cm). Maximal knee
      extension torque, activation level (twitch interpolation technique),
      electromyographic activity of agonist and antagonist muscles, and twitch
      contractile properties were assessed. RESULTS: At preexercise, the maximal
      voluntary isometric and concentric torques of EXPLO were greater than those of
      ENDU (P < 0.05). After the fatiguing exercise, significant isometric (18%; P <
      0.01) and concentric (25%; P < 0.05) torque decreases in EXPLO were associated
      with, respectively, twitch torque (Pt) and maximal rate of twitch development
      (+dPt/dt) reductions (P < 0.01) and with an increase in the antagonist
      coactivation level (P < 0.01). No modification was observed for ENDU.
      Interestingly, the coactivation level was also increased (P < 0.01) in eccentric
      contraction for EXPLO, although the maximal eccentric torque decrease (P < 0.01)
      could not be specifically attributed to any group. CONCLUSION: The fatiguing
      exercise induced central and peripheral adaptations, but the mechanisms differed
      regarding the contraction mode. At pre- and postfatiguing exercise, it seems that
      the neuromuscular profile depends on the subject's training background and the
      contraction modes used to assess fatigue.

PMID- 17218898
TI  - Knee-muscle activation during landings: developmental and gender comparisons.
AB  - PURPOSE: This study determined anteroposterior knee-joint muscle activation
      differences among children and adult males and females landing from a self
      initiated vertical jump (VJ) under normal and offset-target conditions to further
      understand physical maturation's influence on anterior cruciate ligament (ACL)
      injury risk. METHODS: Fifty-five recreationally active volunteer subjects grouped
      by age (children = 9.5 +/- 0.9 yr; adult = 23.9 +/- 2.8 yr) and gender (females =
      28; males = 27) completed motion analysis, ground reaction force, and surface
      electromyography (SEMG) data collection during a two-footed landing under
      straight (midline-target) and offset-target (adult = 45.7 cm; child = 30.5 cm)
      conditions. Target height was 50% of maximum VJ height. Co-contraction ratios
      (CCR) (hamstrings (HAMS)/vastus medialis (VM) activity) from normalized SEMG root
      mean squares were analyzed in the prelanding (PRE) (100 ms before initial contact
      (IC)), reflexive (REF) (100 ms after IC), and voluntary (VOL) (end of REF to
      maximum knee flexion) muscle activity phases. Repeated-measures statistical
      analyses determined significant gender, physical maturation, and target
      differences (P < 0.05) in CCR and associated HAMS and VM activity across landing
      phases. RESULTS: A significant interaction (P < 0.0001) indicated similar CCR for
      children and adults during the REF and VOL phases, but during the PRE phase adult
      CCR (619.04 + 52.01) were two times greater than children's (308.32 +/- 51.04).
      Significantly more HAMS activity, not less VM activity, increased adult PRE-CCR.
      Gender and target CCR differences were absent. CONCLUSIONS: Children's decreased
      preparatory co-contraction about the knee does not seem to be linked to increased
      ACL injury risk. Thus, adults may strive for preparatory co-contraction levels
      about the knee that permit adaptability to varied landing tasks.

PMID- 17218899
TI  - Aerodynamic characteristics as determinants of the drafting effect in cycling.
AB  - PURPOSE: To determine whether cyclists' individual aerodynamic characteristics
      influence the magnitude of the drafting effect in cycling. METHODS: Thirteen
      competitive male cyclists performed two field protocols (individual and
      drafting). Hub-based power meters were used to measure power output and velocity,
      from which drag area (Ad) was calculated. The three subjects obtaining maximum
      (MAX), intermediate (INT), and minimum (MIN) values for Ad during the individual
      protocol acted as leaders during the drafting protocol. Measures of Ad were then
      made while subjects drafted each of the three leaders. The drafting effect was
      specifically quantified as the decrement on measured drag coefficient (Cd) and
      power output. RESULTS: The mean drafting effect increased with leader Ad
      (DeltaCd: MIN = 35.55%, INT = 41.31%, MAX = 50.47%; Delta power: MIN = 111.1 W,
      INT = 124.05 W, MAX = 159.23 W; P < 0.0001). Regressions between leader Ad and
      drafting effect for individual drafters indicated substantial interdrafter
      variability (slope ranged from 29.4 to 190.5%.m) but little intradrafter
      variability (mean r = 0.9689), suggesting an interaction between leader and
      drafter. Correlating leader:drafter ratios for Ad, Ap, and body mass to the
      drafting effect supported this interaction (r = 0.69-0.78, P < 0.01), but only
      when data for all three groups were pooled. CONCLUSIONS: Alteration of leader Ad
      elicits a linear increase in the drafting effect. However, the Ad of the leader
      does not explain all of the interdrafter variability in the drafting effect,
      which is specific to the drafting subject but is minimally explained by their
      aerodynamic characteristics. This interdrafter variability may be attributable to
      the drafter's skill in obtaining maximum benefit from drafting.

PMID- 17218900
TI  - Effects of hiking downhill using trekking poles while carrying external loads.
AB  - Hiking is a recreational activity shown to offer significant positive effects on
      the human body. However, walking downhill and external load carriage have both
      been shown to increase the risk of musculoskeletal pain and injury. The use of
      hiking poles has been demonstrated to be successful in reducing forces placed on
      the lower extremities. However, whether these effects can be observed with load
      carriage has not been examined. PURPOSE: The purpose of this research was to
      examine the effectiveness of pole use in hiking downhill while carrying different
      external loads. METHODS: Fifteen experienced male hikers volunteered. Conditions
      included hiking with and without the use of hiking poles for each of three
      backpack conditions (no pack, day pack (15% BW), and large expedition pack (30%
      BW). Ten trials were completed for each condition, for a total of 60 trials per
      participant. All conditions were performed in a random order. The net joint
      moments and power at the ankle, knee, and hip, as well as the net joint forces at
      the knee were examined statistically using a 2 x 3 (poles x packs) repeated
      measures ANOVA, with a family wise alpha level of 0.05. RESULTS: A significant
      reduction was observed for the sagittal plane moment at each of the joints in the
      lower extremity with pole use. Reductions were also observed in the peak power
      absorption for the ankle and knee. These results held true across pack
      conditions, as packs only resulted in a larger power generation at the hip.
      CONCLUSION: A reduction in the forces, moments, and power around the joint, with
      the use of poles, will help reduce the loading on the joints of the lower
      extremity.

PMID- 17218901
TI  - Influence of nutrient intake after weigh-in on lightweight rowing performance.
AB  - PURPOSE: The aim of the present study was to compare the effectiveness of
      different nutritional recovery strategies between weigh-in and racing on 2000-m
      rowing ergometer performance among oarsmen undertaking short-term weight loss
      before competition. METHODS: Competitive rowers (N = 12) completed four ergometer
      trials, each separated by 48 h. No weight restrictions were imposed for the first
      trial (TR1). Thereafter, athletes were required to reduce their body mass by 5.2%
      in the 24 h before trial 2 (TR2), again reaching this body mass before the final
      two trials (TR3 and TR4). Athletes were provided with one of three nutritional
      recovery strategies in the 2 h between weigh-in and racing in a counterbalanced
      fashion according to a Latin square design: fluid (2.8 kJ.kg(-1), 0.0 g.kg(-1)
      carbohydrate, 0.6 mg.kg(-1) sodium, 28.5 mL.kg(-1) fluid; FLU),
      carbohydrate/sodium (45.3 kJ.kg(-1), 2.2 g.kg(-1) carbohydrate, 32.9 mg.kg(-1)
      sodium, 7.2 mL.kg(-1) fluid; CHO), and a combination of water and
      carbohydrate/sodium (44.8 kJ.kg(-1), 2.3 g.kg(-1) carbohydrate, 33 mg.kg(-1)
      sodium, 28.5 mL.kg(-1) fluid; COM). RESULTS: Performance was slower for CHO
      compared with both COM (mean difference, 4.13; 95% CI, 1.37-6.88 s; P = 0.003)
      and FLU (2.88; 95% CI, 0.13-5.63 s; P = 0.039). However, FLU was not
      significantly slower than COM (1.24; 95% CI, -1.41 to 3.90 s; P = 0.474).
      CONCLUSIONS: The present investigation has shown that although carbohydrate and
      sodium intake may be important in the recovery period between weigh-in and 2000-m
      rowing ergometer performance, fluid intake has a greater influence on performance
      among lightweight male rowers who undertake short-term weight loss to achieve
      specified body-mass limits.

PMID- 17218902
TI  - Estimation of oxygen uptake during fast running using accelerometry and heart
      rate.
AB  - Previous investigations have reported that accelerometer counts plateau during
      running at increasingly faster speeds. PURPOSE: To assess whether biomechanical
      and/or device limitations cause this phenomenon and the feasibility of generating
      oxygen uptake (.VO2) prediction equations from the combined use of accelerometry
      and heart rate during walking and running. METHODS: : Sixteen endurance-trained
      subjects completed two exercise tests on a treadmill. The first was a continuous
      incremental test to volitional exhaustion to determine ventilatory threshold and
      peak .VO2. The second was a discontinuous incremental exercise test while walking
      (3, 5, and 7 km.h(-1)) and running (8, 10, 12, 14, 16, 18, and 20 km.h(-1), or
      until volitional exhaustion). Subjects completed 3 min of exercise at each speed,
      followed by 3-5 min of recovery. Activity counts from uni- and triaxial
      accelerometers, heart rate, and gas exchange were measured throughout exercise.
      RESULTS: All accelerometer outputs rose linearly with speed during walking.
      During running, uniaxial accelerometer outputs plateaued, whereas triaxial output
      rose linearly with speed up to and including 20 km.h(-1). Prediction of .VO2
      during walking and running using heart rate (R2 = 0.42 and 0.59, respectively),
      accelerometer counts (R2 = 0.48-0.83 and 0.76, respectively), the combined
      methodologies (R2 = 0.54-0.85 and 0.80, respectively), and the combined
      methodologies calibrated with individual data (R2 = 0.99-1.00 and 0.99,
      respectively) was completed by linear regression. CONCLUSIONS: Uni- and triaxial
      accelerometer outputs have a linear relationship with speed during walking.
      During running, uniaxial accelerometer outputs plateau because of the
      biomechanics of running, whereas triaxial accelerometer output has a linear
      relationship. The combined methodologies predict .VO2 better than either
      predictor alone; a subject's individually calibrated data further improves .VO2
      estimation.

PMID- 17218903
TI  - Cognitive performance in older women relative to ApoE-epsilon4 genotype and
      aerobic fitness.
AB  - INTRODUCTION: Apolipoprotein E (ApoE) genotype and aerobic fitness are each
      associated with cognitive performance in older adults. However, their potentially
      interactive effects on cognitive performance have not been examined. PURPOSE: The
      primary purpose of this study was to determine whether ApoE genotype and aerobic
      fitness interact to uniquely impact memory performance and executive functioning.
      A secondary purpose was to examine the interactive effects on other measures of
      cognition to provide a more comprehensive assessment of cognitive abilities
      across a broad range of functions. METHODS: Community-dwelling, cognitively
      normal older women (N = 90) provided blood samples to allow for assessment of
      ApoE genotype, completed cognitive tests, and performed a maximal aerobic fitness
      test. Primary outcome variables were the auditory verbal learning test (AVLT),
      the complex figures test (CFT), and the Wisconsin card-sorting task (WCST).
      Secondary outcome variables were the block design test and the paced auditory
      serial addition task (PASAT). RESULTS: Regression analyses indicated that aerobic
      fitness was associated with significantly better performance on measures of the
      AVLT, the CFT, and the PASAT for the ApoE-epsilon4 homozygotes. CONCLUSION: The
      preliminary findings from this study support the possibility that aerobic fitness
      is positively associated with the memory performance of those individuals at most
      genetic risk for Alzheimer disease.

PMID- 17218904
TI  - Acute weight cycling versus long-term judo practice in male and female judoists.

PMID- 17218906
TI  - Validity of skinfolds to measure change.

PMID- 17218909
TI  - Reducing the risk of endophthalmitis following intravitreal injections.

PMID- 17218907
TI  - Molecular pathology of eyes with von Hippel-Lindau (VHL) Disease: a review.
AB  - BACKGROUND: von Hippel-Lindau Disease (VHL) is an autosomal dominant inherited
      systemic cancer syndrome. Recently, many advances have contributed to the
      understanding of VHL pathophysiology. METHODS: In this article we review recent
      developments and summarize our findings in VHL molecular pathology related to
      retinal and optic nerve diseases. RESULTS: Loss of heterozygosity (LOH) within
      the VHL gene is detected in the stromal cells surrounding the capillary
      endothelial cells and admixed with glial cells in ocular hemangioblastomas. This
      finding is in line with similar findings in VHL-associated CNS hemangioblastoma
      and renal clear cell carcinomas. Increases of vascular endothelial growth factor
      (VEGF), hypoxia induced factor (HIF), and ubiquitin are found in ocular
      hemangioblastomas.Interestingly, tumorlet cells, which are composed of poorly
      differentiated small cells with prominent dark nuclei and little cytoplasm, as
      well as several stem cell markers, such as erythropoietin (Epo), Epo receptor
      (EpoR), and CD133, are present in ocular VHL lesions. CXCR4, a CXC chemokine
      receptor is also expressed in retinal VHL hemangioblastomas. CONCLUSIONS: These
      findings imply that VHL cells with LOH of the tumor suppressor gene, most likely
      originate from a hematopoietic/vascular lineage. Targeting these proteins and
      ischemic factors, not VEGF alone, may be a potential therapeutic approach for VHL
      associated ocular hemangioblastomas.

PMID- 17218910
TI  - Short-term effects of focal argon laser treatment in diabetic maculopathy as
      demonstrated by optical coherence tomography.
AB  - PURPOSE: To assess the short-term effects of argon laser on retinal thickening as
      demonstrated by optical coherence tomography (OCT). METHODS: A prospectively
      collected consecutive series of patients undergoing routine focal argon laser
      treatment for sight-threatening diabetic maculopathy had bilateral OCT performed
      before laser treatment and 1 hour, 24 hours, and 2 weeks after treatment. The
      main outcome measure was change in retinal thickness in the region of laser
      treatment. RESULTS: Forty-six eyes were analyzed. There was a small increase in
      retinal thickness in the treated area 1 hour after laser treatment, with a mean
      change from before laser treatment of +2.6 microm (95% confidence interval [CI],
      +0.2 to + 5.0). However, there was a larger change 24 hours after treatment of
      +39.0 microm (95% CI, +31.6 to + 46.4) and a significant decrease 2 weeks after
      treatment of -14.6 microm (95% CI, -21.6 to -7.7) from before laser treatment
      values. CONCLUSION: Focal argon laser treatment remains the first-line treatment
      for sight-threatening diabetic maculopathy. This study shows that in the short
      term, areas of retinal thickening worsen before settling in response to argon
      laser treatment as demonstrated by OCT.

PMID- 17218911
TI  - Fundus microperimetry patterns of fixation in type 2 diabetic patients with
      diffuse macular edema.
AB  - BACKGROUND: Recently developed fundus microperimetry (MP-1; Nidek Technologies,
      Srl. Vigonza PD, Italy) was used to evaluate fixation patterns and retinal
      sensitivity in patients who had clinically significant macular edema with a
      diffuse pattern and type 2 diabetes mellitus. METHODS: In a prospective,
      observational case series study, 84 consecutive patients with type 2 diabetes (84
      eyes) who had clinically significant macular edema with a diffuse pattern were
      studied by means of MP-1. Main outcome measures were fixation stability and
      position and mean retinal sensitivities within the central 2 degrees and 8
      degrees areas. Logarithm of the minimum angle of resolution (logMAR) best
      corrected visual acuity (BCVA) was evaluated by means of an Early Treatment of
      Diabetic Retinopathy Study chart. Foveal thickness was measured by Stratus
      optical coherence tomography (OCT; Carl Zeiss Meditec, Inc., Dublin, CA). Age,
      duration of diabetes, hemoglobin A1c (HbA1c) levels, duration of symptoms,
      history of panretinal photocoagulation, vitreomacular adhesion, and cystoid
      macular changes were documented. Patients were grouped according to both position
      of fixation (central or eccentric) and stability of fixation (stable or
      unstable). Statistical analyses included independent samples t-test, binomial
      test, Bonferroni correction for multiple comparisons, and generalized linear
      model univariate analysis. RESULTS: Of 84 eyes, 44 (52.4%) had central fixation,
      and 40 (47.6%) had eccentric fixation. Of 84 eyes, 34 (40.5%) had stable
      fixation, and 50 (59.5%) had unstable fixation. In the whole sample, mean central
      2 degrees retinal sensitivity +/- SD was 6.26 +/- 3.19 dB (range, 0-14.80 dB),
      and mean central 8 degrees retinal sensitivity +/- SD was 7.62 +/- 2.55 (range,
      3.85-14.90 dB); logMAR BCVA ranged from 0.1 to 1.3 (mean +/- SD, 0.6 +/- 0.29).
      Mean OCT foveal thickness +/- SD was 300.77 +/- 66.93 m (range, 220-525 m). Both
      comparisons between groups (stable vs. unstable and central vs. eccentric) showed
      statistically significant differences in mean logMAR BCVA, mean central 2 degrees
      and 8 degrees retinal sensitivities, and mean OCT foveal thickness. Duration of
      symptoms was significantly longer and HbA1c levels were higher in the groups with
      deterioration of stability or centrality of fixation. The prevalence of cystoid
      macular changes was significantly higher in the groups with eccentric or unstable
      fixation (P < 0.001). Generalized linear model statistical analysis showed that
      logMAR BCVA was significantly associated with stability of fixation (P = 0.020),
      mean central 8 degrees retinal sensitivity (P < 0.001), and mean OCT foveal
      thickness (P < 0.001). The interaction between stability of fixation and mean OCT
      foveal thickness showed a statistically significant association with logMAR BCVA
      (P = 0.003). Some eyes with eccentric fixation presented with stable fixation,
      especially in the presence of long-lasting symptoms, and had better visual acuity
      than eyes with central, but unstable fixation. CONCLUSION: Visual acuity, central
      retinal sensitivity, foveal thickness, duration of symptoms, HbA1c levels, and
      presence of cystoid macular changes were strongly associated with fixation
      impairment in type 2 diabetic patients who had clinically significant macular
      edema with a diffuse pattern. Stability of fixation and foveal thickness play a
      major role in conditioning BCVA.

PMID- 17218912
TI  - Retinal function after scleral buckling for recent onset rhegmatogenous retinal
      detachment: assessment with electroretinography and optical coherence tomography.
AB  - PURPOSE: To investigate central and peripheral retinal function after scleral
      buckling surgery for recent onset rhegmatogenous retinal detachment (RD).
      METHODS: Fifteen phakic patients with rhegmatogenous RD for <1 week underwent
      scleral buckling surgery. Clinical investigation, optical coherence tomography
      (OCT), full-field electroretinography (ERG), and multifocal ERG (mfERG) with
      fundus illumination were performed preoperatively and 6 months postoperatively.
      RESULTS: Anatomical success was achieved in 14 patients. mfERG amplitudes were
      reduced preoperatively in detached retina, with significant improvement at follow
      up (P = 0.002). Foveal amplitudes improved significantly (P = 0.027). There was
      no significant difference in postoperative mfERG amplitudes between areas that
      had been preoperatively detached or attached (P = 0.739). In the subgroup of
      eight patients in whom the detachment engaged the fovea preoperatively, rod
      function improved significantly as assessed with full-field ERG (P = 0.008). In
      these patients, the extent of detachment ranged between 4 clock hours and 6 clock
      hours, as compared with 2 clock hours and 5 clock hours in the remaining
      patients. OCT showed subretinal foveal fluid in four patients at follow-up.
      CONCLUSIONS: In recent onset rhegmatogenous RD, total rod and localized central
      retinal dysfunction in detached retina can improve significantly after
      reattachment. mfERG and OCT are suitable tools for further studies of functional
      outcomes in RD.

PMID- 17218913
TI  - Anatomical and visual outcomes after episcleral macular buckling compared with
      those after pars plana vitrectomy for retinal detachment caused by macular hole
      in highly myopic eyes.
AB  - PURPOSE: To report anatomical and visual outcomes after episcleral macular
      buckling (EMB) and pars plana vitrectomy (PPV) for retinal detachment caused by
      macular hole in highly myopic eyes with posterior staphyloma. PATIENTS AND
      METHODS: This retrospective, interventional case series included 58 eyes of 58
      patients with retinal detachment caused by macular hole in highly myopic eyes
      with posterior staphyloma and geographic chorioretinal atrophy. The cases were
      assigned to 2 groups according to the surgical technique: the EMB group (30 eyes)
      underwent posterior episcleral buckling using a solid silicone plate specifically
      designed for macular indentation, and the PPV group (28 eyes) underwent PPV
      combined with fluid-gas exchange. Baseline clinical data including age, sex,
      refractive errors, and degree of retinal detachment did not differ between EMB
      and PPV groups. Main outcome measures included ophthalmoscopy findings, three
      mirror contact lens biomicroscopy results, and visual acuity at the end of follow
      up (mean follow-up, 52.8 months in the EMB group and 44.1 months in the PPV
      group). Optical coherence tomography was performed in selected cases in the EMB
      group. RESULTS: In the EMB group, the retinal reattachment rate was 93.3% after
      primary surgery and 100% after secondary surgery. In the PPV group, the retinal
      reattachment rate was 50% after primary surgery and 86% after secondary surgery
      using the EMB procedure, thus indicating a better anatomical success rate after
      primary EMB than after primary PPV. The mean logarithm of the minimum angle of
      resolution (logMAR) visual acuity +/- SD in the EMB group increased significantly
      from 1.45 +/- 0.50 before surgery to 0.92 +/- 0.42 at the end of follow-up (P <
      0.001). The mean logMAR visual acuity in the PPV group increased significantly
      from 1.70 +/- 0.45 before surgery to 1.35 +/- 0.61 at the end of follow-up (P <
      0.02). Visual acuity improvement at the end of follow-up was significantly better
      after EMB than after PPV (P < 0.005). Optical coherence tomography revealed that
      10 of 12 eyes with successful indentation of the macular hole area after EMB had
      complete closure of the macular hole as well as reattachment of the retina, and
      the remaining 2 eyes had persistent retinal reattachment with the foveal defect.
      CONCLUSIONS: EMB is a preferred surgical procedure for the repair of retinal
      detachment and macular hole closure in highly myopic eyes with posterior
      staphyloma.

PMID- 17218914
TI  - Eccentric macular holes after vitrectomy with peeling of epimacular
      proliferation.
AB  - PURPOSE: To describe six patients (six eyes) who developed an eccentric macular
      hole after surgery for idiopathic epimacular proliferation. METHODS: In a
      retrospective review of 631 consecutive patients who underwent vitrectomy with
      peeling of the epimacular proliferation and in most cases the internal limiting
      membrane (ILM) from May 2001 to May 2005, 6 patients were found to have developed
      an eccentric macular hole postoperatively. RESULTS: Eccentric macular holes
      developed 9 days to 8 months (mean, 3.1 months) after epimacular proliferation
      peeling. The ILM was peeled in addition to the epimacular proliferation in five
      of the six cases. Of the six eccentric macular holes, four were located temporal
      to the fovea, one was located superior to the fovea, and one was located nasal to
      the fovea. Final visual acuities after a mean follow-up period of 17.3 months
      were 20/20 in 2 eyes, 20/25 in 1 eye, 20/40 in 2 eyes, and 5/200 in 1 eye. The
      eye with the eccentric macular hole nasal to the fovea had the poorest final
      visual acuity of 5/200. CONCLUSION: Eccentric macular hole occurring after
      vitrectomy to remove epimacular proliferation is an uncommon postoperative
      finding. To our knowledge, this is the largest case series of such patients
      reported. Various explanations have been suggested for the etiology of these
      holes, but there remains no consensus.

PMID- 17218915
TI  - Long-term outcomes of vitrectomy with or without arteriovenous sheathotomy in
      branch retinal vein occlusion.
AB  - PURPOSE: To evaluate the long-term effect of vitrectomy with or without
      arteriovenous sheathotomy for macular edema secondary to branch retinal vein
      occlusion (BRVO). METHODS: The study was a prospective, randomized, comparative,
      interventional case series of 36 patients (36 eyes) who underwent pars plana
      vitrectomy with or without arteriovenous sheathotomy for macular edema due to
      BRVO of <or=8 weeks' duration of symptoms. Eighteen eyes with arteriovenous
      sheathotomy (sheathotomy group) were compared with 18 eyes without sheathotomy
      (vitrectomy group). Main outcomes measures were best-corrected visual acuity and
      central foveal thickness as evaluated by optical coherence tomography. RESULTS:
      Baseline demographic characteristics of the groups were similar. Postoperative
      follow-up period ranged from 12 months to 45 months (31 months). Median best
      corrected visual acuity significantly improved from 0.4 at baseline to 1.0 at the
      final visit in both groups, and there was no significant difference in best
      corrected visual acuity at any postoperative period between the groups. Of 16
      patients with duration of symptoms of <4 weeks, those with arteriovenous
      sheathotomy had a tendency toward better visual outcomes than those without
      arteriovenous sheathotomy (P = 0.064). The central foveal thickness also
      significantly decreased after surgery in both groups, but the differences were
      not significant for the two groups at each time point. No patients had severe
      intraoperative and/or postoperative complications. CONCLUSIONS: Our findings
      suggest that vitrectomy with or without arteriovenous sheathotomy may improve the
      long-term functional and tomographic outcomes for patients with macular edema
      secondary to BRVO. Although additional arteriovenous sheathotomy did not lead to
      a distinct functional benefit in this series, early surgical intervention may
      result in better visual outcomes.

PMID- 17218916
TI  - Conjunctival epithelium in pars plana vitrectomy specimens.
AB  - PURPOSE: To review histopathology of vitrectomy specimens obtained during routine
      pars plana vitrectomy (PPV) for evidence of inadvertent introduction of
      conjunctival epithelium into the vitreous cavity during PPV. METHODS:
      Retrospective review of all vitreous specimens obtained from PPV over a 3-year
      period during which vitreous samples were routinely submitted from routine and
      diagnostic PPV. Patient charts and operative reports were reviewed, with
      particular attention to history of postoperative endophthalmitis, and the use of
      transconjunctival PPV. RESULTS: A total of 650 specimens were obtained over a 3
      year period. Three specimens with conjunctival epithelium were identified. None
      of these cases resulted in endophthalmitis. Two of these three cases used
      transconjunctival techniques. In one case all three sclerotomies were made using
      transconjunctival techniques. CONCLUSIONS: The presence of conjunctiva in the
      vitreous aspirate from completely transconjunctival PPV indicates that
      conjunctival epithelium can be inadvertently introduced into the vitreous cavity
      during PPV. Although none of these cases resulted in endophthalmitis, special
      care to sterilize the conjunctiva before the creation of transconjunctival
      sclerotomies is warranted.

PMID- 17218917
TI  - Optical coherence tomography findings in nonproliferative group 2a idiopathic
      juxtafoveal retinal telangiectasis.
AB  - PURPOSE: To determine the optical coherence tomography (OCT) findings in eyes
      with group 2a idiopathic juxtafoveal retinal telangiectasis (IJRT). METHODS:
      Forty-one eyes of 22 patients with nonproliferative group 2a IJRT were examined.
      OCT testing including retinal topographic mapping and analysis, and horizontal
      and vertical line scans, was obtained on each eye. RESULTS: None of the 41 eyes
      had a thickened foveal center. The average center foveal thickness was 166 microm
      (31-264 microm). Stage 1 eyes (n = 2) were normal fellow eyes in patients with
      contralateral group 2a IJRT. Stage 2 eyes (n = 11) all had parafoveolar temporal
      graying and intraretinal temporal fluorescein leakage, but rarely had
      photoreceptor disruption (18%) on OCT testing. Stage 3 eyes (n = 14) all had
      clinical and fluorescein findings similar to or more pronounced than stage 2
      eyes. All stage 3 eyes also had one or more foveal cysts at various retinal
      depths on OCT. Most of these eyes (86%) had photoreceptor disruption and outer
      retinal atrophy on OCT. Stage 4 eyes (n = 14) all had a black foveal or
      parafoveolar pigment plaque and intraretinal temporal fluorescein leakage. All
      stage 4 eyes had a hyper-reflective plaque with shadowing on OCT corresponding to
      the pigment plaque. Most of these eyes had one or more foveal cysts (64%) and all
      of these eyes had photoreceptor disruption and outer retinal atrophy. CONCLUSION:
      OCT helps in the staging of group 2a IJRT and reveals multiple retinal structural
      abnormalities.

PMID- 17218918
TI  - Intravitreal gnathostomiasis and review of literature.
AB  - Intravitreal gnathostomiasis is a rare disease. To our knowledge, only five case
      reports are available in the literature wherein the parasites were surgically
      removed from the vitreous cavity and the species were identified. In this report,
      we document the clinical features of intravitreal gnathostomiasis along with the
      route of entry and parasitic migration pattern in ocular tissue, surgical
      management, and electron microscopic features of the retrieved advanced third
      stage larva of Gnathostoma spinigerum (aL3) for a 48-year-old Indian woman with
      excellent postsurgical visual recovery.

PMID- 17218919
TI  - Steamroller versus basic technique in pneumatic retinopexy for primary
      rhegmatogenous retinal detachment.
AB  - PURPOSE: To compare the effectiveness and safety of the "basic" technique with
      those of the "steamroller" technique in pneumatic retinopexy (PR) for primary
      rhegmatogenous retinal detachment. METHODS: In this prospective study, 40 eyes of
      40 patients with primary rhegmatogenous retinal detachment were treated with PR
      by argon laser photocoagulation. PR with the steamroller technique (steamroller
      group) was performed randomly on 21 eyes of 21 patients, and 19 eyes of 19
      patients were treated with PR with the basic technique (basic group). Main
      outcome measures were visual acuity, anatomical outcome, rate of proliferative
      vitreoretinopathy (PVR) development, and postoperative complications. RESULTS:
      Mean follow-up +/- SD was 14.7 +/- 9.9 months (range, 6-48 months). Single
      operation success rate for all patients was 70% (28/40 eyes). Single-operation
      success rate was 74% (14/19 eyes) for the basic group and 67% (14/21 eyes) for
      the steamroller group (P = 0.629). PVR grade C-1 developed in one eye (5%) in
      each group. Overall success rate, after reoperations, was 100% for each group.
      Preoperative logMAR (logarithm of the minimum angle of resolution) visual acuity
      +/- SD was 2.01 +/- 0.43 in the basic group and 1.89 +/- 0.45 in the steamroller
      group (P = 0.434). Postoperative logMAR visual acuity +/- SD was 0.64 +/- 0.42 in
      the basic group and 0.46 +/- 0.35 in the steamroller group (P = 0.152). There was
      no statistically significant difference between basic and steamroller groups in
      terms of postoperative complications (P > 0.05). CONCLUSION: Basic and
      steamroller techniques appear to be equally effective and safe in PR for primary
      rhegmatogenous retinal detachment. The risk for PVR development seems to be
      similar with either technique. Further studies with a large number of patients
      are required for a more reliable conclusion.

PMID- 17218920
TI  - A novel method to oxygenate intraocular irrigation fluids with an in-line
      oxygenator.
AB  - PURPOSE: We describe a novel method to oxygenate intraocular irrigation solutions
      involving an in-line oxygenator. METHODS: Either lactated Ringer (LR) solution or
      balanced salt solution (BSS) was oxygenated with the FE390 Stainless In-line
      Oxygenation Assembly (Beer, Beer, and More Beer, Concord, CA). After running a
      100-mL of solution through the in-line oxygenator, oxygen saturation was measured
      with a dissolved oxygen meter. A control experiment involving the oxygenator
      without oxygen perfusion was performed. Paired t-tests were used to compare
      oxygen saturation changes before and after oxygenation. RESULTS: In comparison
      with the original BSS, there was an increase in oxygen saturation of 162 +/- 47%
      (n = 40; P < 0.05). Without oxygenation perfusion, there was only a 24 +/- 14% (n
      = 40) increase in oxygen levels in BSS, which was significantly lower than that
      in treated BSS (P < 0.05). In comparison with the original LR solution, there was
      an increase in oxygen saturation of 208 +/- 21% (n = 40; P < 0.05). Without
      oxygenation perfusion, there was only a 21 +/- 9% (n = 40) gain in oxygen
      saturation in the control LR solution, which was statistically lower as well (P <
      0.05). CONCLUSION: The in-line oxygenator is an efficient tool for oxygenating
      BSS and LR solution. It represents a potential efficient and convenient method to
      oxygenate irrigating solutions for vitreoretinal surgeries.

PMID- 17218921
TI  - Effect of oxygenated intraocular irrigation solutions on the electroretinogram
      after vitrectomy.
AB  - PURPOSE: To investigate the effect of oxygenated intraocular irrigating solutions
      on electroretinograms (ERGs) for postvitrectomy rabbits. METHODS: Eight groups of
      five rabbits each underwent pars plana vitrectomy on the right eye; the left eye
      of each rabbit served as control. The intraocular irrigating solutions were
      balanced salt solution (BSS), BSS-plus, BSS + oxygen (BSS + O2), BSS-plus + O2,
      and combinations of each with the addition of endoillumination (L). All animals
      were evaluated by single-flash scotopic electroretinography on the operated and
      nonoperated eyes before surgery and at 1 hour, 1 day, 1 week, and 1 month after
      surgery by an unmasked observer. The main outcome measures were dark-adapted b
      wave amplitudes of operated eye/nonoperated eye ratios. The results for the
      different groups were compared by analysis of variance. RESULTS: Mean dark
      adapted b-wave amplitudes of operated eye/nonoperated eye ratios +/- SD for BSS
      plus and BSS-plus + O2 before surgery and 1 hour, 1 day, 1 week, and 1 month
      after surgery were 1.01 +/- 0.09, 0.50 +/- 0.11, 0.95 +/- 0.11, 0.97 +/- 0.11,
      and 0.99 +/- 0.08 and 0.98 +/- 0.08, 0.59 +/- 0.10, 0.92 +/- 0.06, 0.97 +/- 0.08,
      and 0.97 +/- 0.10, respectively. At both 1 hour and 1 day after surgery, rabbits
      treated with BSS-plus + O2 had an earlier b-wave return to baseline findings, but
      the differences were not statistically significant (P > 0.05). Mean dark-adapted
      b-wave amplitudes of operated eye/nonoperated eye ratios +/- SD for BSS and BSS +
      O2 before surgery and 1 hour, 1 day, 1 week, and 1 month after surgery were 1.02
      +/- 0.10, 0.47 +/- 0.09, 0.77 +/- 0.07, 0.89 +/- 0.07, and 0.89 +/- 0.07 and 1.02
      +/- 0.06, 0.62 +/- 0.16, 0.94 +/- 0.09, 0.97 +/- 0.08, and 0.96 +/- 0.06,
      respectively. One hour and 1 day after surgery, ERG readings for rabbits treated
      with BSS + O2 exhibited a statistically significantly earlier return of ERG
      voltage to baseline values compared with both BSS and BSS + L (P = 0.05 and P =
      0.02, respectively). One day after surgery, rabbits treated with BSS alone had
      the lowest ERG ratios. One week and 1 month after surgery, for all solutions
      tested other than BSS, ERG values were within normal limits. CONCLUSION: The use
      of oxygenated solutions appears to affect ERG readings after pars plana
      vitrectomy. Further studies to evaluate the role of oxygenated solutions in
      different vitreoretinal surgical procedures are warranted.

PMID- 17218922
TI  - Natural history of foveolar lucencies observed by optical coherence tomography
      after macular hole surgery.
AB  - PURPOSE: To describe the incidence, course, and anatomic and functional outcomes
      of foveolar lucencies observed by optical coherence tomography after macular hole
      surgery. METHODS: Retrospective chart review of all idiopathic macular hole
      surgeries performed between February 2002 and August 2003. Available data
      involving eyes with foveolar lucencies after macular hole surgery were collected
      regarding best-corrected visual acuity, lens status, slit-lamp biomicroscopy, and
      optical coherence tomography before and at follow-up visits ranging from 1 week
      to 27 months after macular hole surgery. RESULTS: Thirty-five eyes of 35 patients
      were identified. Foveolar lucencies were detected by optical coherence tomography
      in 9 of the 35 eyes (26%). Operative procedures included creation of a posterior
      vitreous detachment in 8 eyes and indocyanine green-assisted internal limiting
      membrane peeling in 5 eyes. Intraocular tamponade consisted of 30% sulfur
      hexafluoride gas in 6 eyes and 20% perfluoropropane gas in 3 eyes with at least 1
      week of face-down positioning. Postoperative visual acuity showed gradual
      improvement coinciding with decreasing size and eventual disappearance (3 to 11
      months) of the foveolar lucency. CONCLUSION: Foveolar lucencies observed by
      optical coherence tomography are a common finding after macular hole surgery
      (26%). They occur with and without indocyanine green-assisted internal limiting
      membrane peeling. Earlier disappearance of the foveolar lucency does not
      correlate with the type of gas used for tamponade. They gradually decrease and
      eventually resolve with time without additional surgical intervention and with
      further improvement of visual acuity.

PMID- 17218923
TI  - Diagnostic and therapeutic challenges.

PMID- 17218924
TI  - Choroidal tuberculoma in pregnancy.

PMID- 17218925
TI  - Persistent cone dysfunction in acute exudative polymorphous vitelliform
      maculopathy.

PMID- 17218926
TI  - New stratusoct findings in extrapapillary excavated anomaly and secondary macular
      complications.

PMID- 17218927
TI  - Posterior uveal metastases from medullary thyroid carcinoma.

PMID- 17218928
TI  - Autofluorescence imaging of optic pit maculopathy.

PMID- 17218929
TI  - Mifepristone treatment of chronic central serous chorioretinopathy.

PMID- 17218930
TI  - Triamcinolone acetonide remaining on the fovea after successful macular hole
      closure.

PMID- 17218931
TI  - Bilateral proliferative retinopathy in chronic myelogenous leukemia.

PMID- 17218933
TI  - The "chemical" approach to removal of Miragel scleral explants.

PMID- 17218934
TI  - Infant deaths associated with cough and cold medications--two states, 2005.
AB  - Cough and cold medications that contain nasal decongestants, antihistamines,
      cough suppressants, and expectorants commonly are used alone or in combination in
      attempts to temporarily relieve symptoms of upper respiratory tract infection in
      children aged <2 years. However, during 2004-2005, an estimated 1,519 children
      aged <2 years were treated in U.S. emergency departments for adverse events,
      including overdoses, associated with cough and cold medications. In response to
      reports of infant deaths after such events, CDC and the National Association of
      Medical Examiners (NAME) investigated deaths in U.S. infants aged <12 months
      associated with cough and cold medications. This report describes the results of
      that investigation, which identified deaths of three infants aged <6 months in
      2005, for which cough and cold medications were determined by medical examiners
      or coroners to be the underlying cause. The dosages at which cough and cold
      medications can cause illness or death in children aged <2 years are not known.
      Food and Drug Administration (FDA)-approved dosing recommendations for clinicians
      prescribing cough and cold medications do not exist for this age group. Because
      of the risks for toxicity, absence of dosing recommendations, and limited
      published evidence of effectiveness of these medications in children aged <2
      years, parents and other caregivers should not administer cough and cold
      medications to children in this age group without first consulting health-care
      provider and should follow the provider's instructions precisely. Clinicians
      should use caution when prescribing cough and cold medications to children aged
      <2 years. Moreover, clinicians should always ask caregivers about their use of
      over-the-counter combination medications to avoid overdose in children from
      multiple medications that contain the same ingredient.

PMID- 17218935
TI  - National and state medical expenditures and lost earnings attributable to
      arthritis and other rheumatic conditions--United States, 2003.
AB  - Arthritis is the leading cause of disability in the United States, potentially
      limiting affected persons from walking a few blocks or climbing a flight of
      stairs. Using Medical Expenditure Panel Survey (MEPS) data, CDC analyzed national
      and state-specific direct costs (i.e., medical expenditures) and indirect costs
      (i.e., lost earnings) attributable to arthritis and other rheumatic conditions
      (AORC) in the United States during 2003. This report describes the results of
      that analysis, which indicated that, in 2003, the total cost of AORC in the
      United States was approximately 128 billion dollars (80.8 billion dollars in
      direct and 47.0 billion dollars in indirect costs), equivalent to 1.2% of the
      2003 U.S. gross domestic product. Total costs attributable to AORC, by
      state/area, ranged from 225.5 million dollars in the District of Columbia to 12.1
      billion dollars in California. Total costs attributable to AORC have increased
      substantially since 1997, and that increase is expected to continue because of
      the aging of the population and increases in obesity and physical inactivity.
      These findings signal the need for broader implementation of effective public
      health interventions, such as arthritis and chronic disease self-management
      programs, which can reduce medical expenditures among persons with AORC.

PMID- 17218936
TI  - Suicide trends and characteristics among persons in the Guarani Kaiowa and
      Nandeva communities--Mato Grosso do Sul, Brazil, 2000-2005.
AB  - Suicide rates among indigenous communities around the world vary substantially;
      in many nations these groups have the highest suicide risk of any identifiable
      cultural or ethnic group. Mato Grosso do Sul is a state in the southwest corner
      of Brazil that borders Bolivia and Paraguay. In 2004, the Guarani, an indigenous
      ethnic group in the region, accounted for 2.6% of Mato Grosso do Sul's population
      (approximately 2,230,702). During 1975-2000, the infant mortality rate decreased,
      and overall life expectancy increased in Mato Grosso do Sul; however, suicide
      increased as a proportion of overall mortality among the Kaiowa and Nandeva
      communities of the Guarani population. In 2000, the National Health Foundation
      (FUNASA) of the Brazilian Ministry of Health (BMH) initiated a study of suicide
      trends and characteristics in these two Guarani communities; data were collected
      during 2000-2005, and epidemiologic assistance was provided by CDC. This report
      summarizes the results of that study, which suggested that the suicide rate among
      Guarani was 19 times higher than the national rate in Brazil and 10 times higher
      than the rate in Mato Grosso do Sul and that suicides disproportionately affected
      Guarani adolescents and young adults. To decrease suicide rates, BMH initiated
      research and prevention programs among the Guarani, and the Guarani initiated
      measures to increase their economic self-sufficiency.

PMID- 17218937
TI  - A mechanistic study of delta-aminolevulinic acid-based photodynamic therapy for
      cutaneous leishmaniasis.

PMID- 17218938
TI  - Imaging the prodrug-to-drug transformation of a 5-fluorouracil derivative in skin
      by confocal Raman microscopy.
AB  - The widespread adoption of transdermal drug delivery has been limited by the
      barrier properties of the outermost layer of the epidermis, the stratum corneum
      (SC). A variety of approaches have been developed to overcome the barrier,
      including the use of a prodrug form of an active therapeutic agent to enhance
      transdermal delivery. Once in the epidermis, the pro-molecule is converted to the
      active drug by endogenous enzymes or simple chemical hydrolysis. The prodrug
      selected for the current studies, 1-ethyloxycarbonyl-5-fluorouracil, is known to
      enhance transdermal delivery of 5-fluorouracil, an important systemic antitumor
      drug. Using confocal Raman microscopy on pigskin biopsies treated with prodrug,
      we are able to image the spatial distribution of both prodrug and drug in the SC
      and viable epidermis, thereby providing information about permeation and
      metabolism. This approach may readily be extended to a variety of dermatological
      processes.

PMID- 17218939
TI  - CDKN2A germline mutations in individuals with cutaneous malignant melanoma.
AB  - Cyclin-dependent kinase inhibitor type 2A (CDKN2A) has been identified as a major
      melanoma susceptibility gene based on the presence of germline mutations in high
      risk melanoma families. In this study, we sought to identify and characterize the
      spectrum of CDKN2A mutations affecting p16 inhibitor of cyclin-dependent kinase
      type 4 (INK4a) in individuals with melanoma using a population-based study
      design. DNA samples from 1189 individuals with incident multiple primary melanoma
      (MPM) and 2424 with incident single primary melanoma unselected for family
      history of melanoma were available for screening of CDKN2A (p16INK4a) mutations.
      Variants were classified for functional impact based on intragenic position,
      existing functional data, sequence, and structural analysis. The impact of
      individual mutations and functional groupings was assessed by comparing
      frequencies in cases of MPM versus cases with a single first primary melanoma,
      and by comparing the reported incidence rates in first-degree relatives. Our
      results show that mutations occur infrequently in these high-risk groups, and
      that they occur mainly in exons 1alpha and 2. Rare coding variants with putative
      functional impact are observed to increase substantially the risk of melanoma.
      With the exception of the variant in position -34 of CDKN2A of known functional
      consequence, the remaining rare variants in the non-coding region have no
      apparent impact on risk.

PMID- 17218940
TI  - Tetracycline protects against dermonecrosis induced by Loxosceles spider venom.
AB  - Envenomation by spiders belonging to the Loxosceles genus (brown spider) often
      results in local dermonecrotic lesions. We have previously shown that Loxosceles
      sphingomyelinase D (SMase D), the venom component responsible for all the
      pathological effects, induced the expression of matrix metalloproteinases (MMPs)
      in rabbits and in human keratinocytic cells. We also showed that the SMase D
      induced apoptosis and MMP expression of keratinocytes was inhibited by
      tetracyclines. We have further investigated the ability of tetracyclines to
      inhibit or prevent the dermonecrotic lesion induced by Loxosceles venom in vivo
      and in vitro models. Primary cultures of rabbit fibroblasts incubated with
      increasing concentrations of venom or SMase D showed a decrease in cell
      viability, which was prevented by tetracyclines. In vivo experiments showed that
      topical treatments with tetracycline of rabbits, inoculated with crude Loxosceles
      intermedia venom or recombinant SMase D, significantly reduced the progression of
      the dermonecrotic lesion. Furthermore, tetracyclines also reduced the expression
      of MMP-2 and prevented the induction of MMP-9. Our results suggest that
      tetracycline may be an effective therapeutic agent for the treatment of cutaneous
      loxoscelism.

PMID- 17218941
TI  - Approaches to identify inhibitors of melanin biosynthesis via the quality control
      of tyrosinase.
AB  - Tyrosinase, a copper-containing glycoprotein, is the rate-limiting enzyme
      critical for melanin biosynthesis in specialized organelles termed melanosomes
      that are produced only by melanocytic cells. Inhibitors of tyrosinase activity
      have long been sought as therapeutic means to treat cutaneous hyperpigmentary
      disorders. Multiple potential approaches exist that could control pigmentation
      via the regulation of tyrosinase activity, for example: the transcription of its
      messenger RNA, its maturation via glycosylation, its trafficking to melanosomes,
      as well as modulation of its catalytic activity and/or stability. However,
      relatively little attention has been paid to regulating pigmentation via the
      stability of tyrosinase, which depends on its processing and maturation in the
      endoplasmic reticulum and Golgi, its delivery to melanosomes and its degradation
      via the ubiquitin-proteasome pathway and/or the endosomal/lysosomal system.
      Recently, it has been shown that carbohydrate modification, molecular chaperone
      engagement, and ubiquitylation all play pivotal roles in regulating the
      degradation/stability of tyrosinase. While such processes affect virtually all
      proteins, such effects on tyrosinase have immediate and dramatic consequences on
      pigmentation. In this review, we classify melanogenic inhibitory factors in terms
      of their modulation of tyrosinase function and we summarize current understanding
      of how the quality control of tyrosinase processing impacts its stability and
      melanogenic activity.

PMID- 17218942
TI  - Identification of a novel CD160+ CD4+ T-lymphocyte subset in the skin: a possible
      role for CD160 in skin inflammation.
AB  - CD160 is a glycosylphosphatidylinositol-anchored cell surface molecule expressed
      by human circulating cytotoxic lymphocytes that correspond to the majority of
      natural killer cell (NK) expressing CD56(dim), TCRgammadelta lymphocytes, and to
      a minor CD8 T-cell subset. CD160 engagement by major histocompatibility complex
      class I molecules triggers by itself both cytotoxic function and cytokine
      production in NK lymphocytes, whereas it provides co-activating signals to TCR
      induced proliferation in T CD8+ lymphocytes. In this study, we analyzed by
      immunohistochemistry the phenotype of lymphocytes infiltrating normal skin and
      inflammatory skin lesions of atopic dermatitis, contact dermatitis, and
      psoriasis. We identified a minor original subset of CD4+ CD160+ T cells
      infiltrating inflammatory lesions. We found that this lymphocyte subset
      localization is not restricted to the skin, as we demonstrated that CD160
      transcripts could be induced in IL-2 or IL-15-activated CD4+ peripheral blood
      lymphocytes. Finally, we report that CD160 acts as a co-activator receptor for
      CD3-induced proliferation of CD4+ CD160+ T cells isolated from inflammatory skin
      lesions. Thus, we hypothesize that the unique CD4+ CD160+ lymphocyte subset plays
      a role in the pathogenesis of skin inflammation.

PMID- 17218944
TI  - Mechanisms of chronic skin ulceration linking lactate, transforming growth factor
      beta, vascular endothelial growth factor, collagen remodeling, collagen
      stability, and defective angiogenesis.
AB  - Up to one million people suffer from chronic skin ulcers in the US. Little is
      known of the mechanisms leading to tissue breakdown, although inadequate
      circulation and ischemia are common elements in most dermal ulcers. Collagen is
      the principal source of mechanical strength in most tissues, and its molecular
      and fibrillar stability is dependent on adequate oxygen supply. In wound repair,
      localized ischemia leads to fibrogenic responses culminating in elevated collagen
      synthesis and remodeling. This study examines factors influencing collagen
      turnover and stabilization before ulceration in "at risk" patients. Severely
      ischemic but uninjured ischemic skin (IS) was compared with patient- and site
      matched non-ischemic skin. Biochemical mechanisms of tissue repair were activated
      in IS, with increased lactate, transforming growth factor-beta, vascular
      endothelial growth factor, collagen synthesis and matrix metalloproteinases
      (MMPs)-1 and 2. The absence of MMP-9 and inflammatory cells confirmed that this
      upregulation was inappropriate and not in response to injury. Molecular stability
      of collagen was reduced in IS, and there was increased susceptibility to enzymic
      degradation. In conclusion, chronic ischemia and long-term hypoxia result in
      elevated collagen remodeling in an oxygen-poor environment. Unstable collagen
      molecules are synthesized together with upregulated MMPs, resulting in collagen
      denaturation, defective angiogenesis, weaker skin, and predisposition to
      ulceration.

PMID- 17218945
TI  - A conditionally replicative, Wnt/beta-catenin pathway-based adenovirus therapy
      for anaplastic thyroid cancer.
AB  - Thyroid cancer affects between 10,000 and 15,000 people per year in the US.
      Typically, this disease can be controlled with surgical resection and radioiodide
      treatment. However, resistance to these conventional therapies is observed in
      some patients, who develop intractable anaplastic thyroid cancer (ATC), for which
      no effective therapies exist. Recently, a sizable fraction of undifferentiated or
      poorly differentiated thyroid cancers were shown to contain mutations in beta
      catenin, an oncogenic protein involved in the etiology of cancers of many
      tissues. We developed a conditionally replicative adenovirus (named 'HILMI')
      which, by virtue of TCF response elements drives E1A and E1B expression,
      replicates specifically in cells with an active Wnt/beta-catenin pathway. We show
      that several thyroid cancer cell lines, derived from undifferentiated or
      anaplastic tissues and possessing an active Wnt/beta-catenin pathway, are
      susceptible to cell killing by HILMI. Furthermore, viral replication in ATC cells
      as xenograft tumors in nude mice was observed, and prolonged survival of mice
      with ATC tumors was observed following administration of the HILMI therapeutic
      vector. The results warrant further development of this therapeutic approach for
      ATC patients.

PMID- 17218946
TI  - Inhibition of tumor growth in vivo by in situ secretion of bispecific anti-CEA x
      anti-CD3 diabodies from lentivirally transduced human lymphocytes.
AB  - Infiltrating T lymphocytes are found in many malignancies, but they appear to be
      mostly anergic and do not attack the tumor, presumably because of defective T
      cell activation events. Recently, we described a strategy for the tumor-specific
      polyclonal activation of tumor-resident T lymphocytes based on the in situ
      production of recombinant bispecific antibodies (bsAbs) by transfected
      nonhematological cell lines. Here, we have constructed a novel HIV-1-based
      lentiviral vector for efficient gene transduction into various human
      hematopoietic cell types. Several myelomonocytic and lymphocytic cell lines
      secreted the anti-carcinoembryonic antigen (CEA) x anti-CD3 diabody in a
      functionally active form with CD3(+) T-cell lines being the most efficient
      secretors. Furthermore, primary human peripheral blood lymphocytes (PBLs) were
      also efficiently transduced and secreted high levels of functional diabody.
      Importantly gene-modified PBLs significantly reduced in vivo tumor growth rates
      in xenograft studies. These results demonstrate, for the first time, the utility
      of lentiviral vectors for sustained expression of recombinant bsAbs in human T
      lymphocytes. Such T lymphocytes, transduced ex vivo to secrete the activating
      diabody in autocrine fashion, may provide a promising route for a gene therapy
      strategy for solid human tumors.

PMID- 17218947
TI  - The use of tissue inhibitors of matrix metalloproteinases to increase the
      efficacy of a tumor necrosis factor/interferon gamma antitumor therapy.
AB  - Owing to its impressive ability to kill tumor cells, especially in combination
      with interferon-gamma (IFNgamma), tumor necrosis factor (TNF) is widely
      appreciated as being a potential systemic therapeutic for the treatment of
      cancer. On the other hand, owing to its proinflammatory activities,
      administration of TNF leads to many systemic side effects and eventually to a
      potentially lethal systemic inflammatory response syndrome (SIRS). However,
      systemic treatment of tumor-bearing mice with TNF/IFNgamma in combination with BB
      94 (a broad-spectrum metalloproteinase inhibitor) confers protection against
      TNF/IFNgamma-induced mortality, whereas preserving the antitumor activity. In
      this study, we investigated the effect of the adenoviral delivery of human tissue
      inhibitors of matrix metalloproteinase (hTIMP)-1 and hTIMP-2 genes on the outcome
      of TNF/IFNgamma antitumor therapy. The dose of adenovirus was limited to 10(8)
      PFU per mouse owing to the additive toxicity of combining it with TNF/IFNgamma
      therapy. Nevertheless, this dose was sufficient to achieve highly efficient
      adenoviral transfer and expression of hTIMP-1 and hTIMP-2 in the liver, but not
      the tumor. Treatment with this low dose of AdhTIMP-1 or AdhTIMP-2 was not enough
      to protect the host against the toxic effects of TNF/IFNgamma. However, it was
      sufficient to show a synergistic effect of hTIMPs with TNF/IFNgamma such that
      tumors regressed significantly faster. Interestingly, only AdTIMP-2 was able to
      prevent relapses after treatment.

PMID- 17218948
TI  - Efficient transfection of tumors facilitated by long-term therapeutic ultrasound
      in combination with contrast agent: from in vitro to in vivo setting.
AB  - Therapeutic ultrasound (TUS) is a promising non-viral clinical approach for the
      delivery of genes. This study demonstrates the efficient delivery and
      localization of DNA in subcutaneous tumors facilitated by TUS application and
      examines the contribution of ultrasound contrast-agent (USCA) addition on
      transfection. The study addresses the importance of in vivo optimization when
      using long-term TUS and USCA based on data achieved in vitro. In vitro results
      showed that transfection of TrampC2 prostate cancer (Pca) cells using genes
      encoding for luciferase and green fluorescent protein was enhanced when DNA and
      Optison were added together and TUS was applied for 20 or 30 min. In vivo results
      showed that the highest transfection was achieved when Optison and DNA were co
      injected intratumorally, and TUS was applied for 20 min. Using Optison
      significantly increased protein distribution in the tumor. However, in vivo
      expression level was decreased by two and four fold at 7 and 14 days,
      respectively, post-TUS. The study establishes the potential of intratumoral
      delivery of DNA-Optison, followed by TUS as an effective, non-toxic, gene
      delivery method that could provide a safe, clinical alternative to current viral
      gene delivery approaches where short-term gene expression is needed.

PMID- 17218949
TI  - Anticancer activity of an adenoviral vector expressing short hairpin RNA against
      BK virus T-ag.
AB  - The human polyomavirus BK (BKV) is oncogenic in rodents and induces malignant
      transformation of rodent cells in vitro. Although its role in human tumorigenesis
      is still debated, BKV represents an excellent model to evaluate molecularly
      targeted antineoplastic approaches. Here, we have tested whether stable
      suppression of the T antigen (T-ag) oncogene expression could inhibit the in
      vitro and in vivo malignant phenotype of BKV-transformed mouse cells. An
      adenovirus vector system that expresses small hairpin RNAs (shRNAs), which are
      converted into active small interfering RNAs (siRNA) molecules against the BKV T
      ag, was developed. This vector was able to inhibit the expression of BKV T-ag
      through a highly efficient in vitro and in vivo delivery of the siRNA molecule.
      In addition, it allowed a stable expression of siRNA for a period of time
      sufficient to elicit a biological effect. Inhibition of T-ag expression results
      in reduction of the in vitro growth rate of BKV-transformed cells, which is, at
      least in part, caused by restoration of p53 activity and induction of apoptosis.
      In vivo studies proved that adenovirus vectors expressing anti-T-ag siRNA were
      able to suppress tumorigenicity of BKV-transformed cells. Moreover, adenovirus
      vector direct treatment of growing tumors resulted in a significant reduction of
      tumor growth. This study indicates that siRNAs delivery via a viral vector have a
      potential usefulness as in vivo anticancer tool against viral and cellular
      oncogenes.

PMID- 17218950
TI  - Delivery of replication-competent retrovirus expressing Escherichia coli purine
      nucleoside phosphorylase increases the metabolism of the prodrug, fludarabine
      phosphate and suppresses the growth of bladder tumor xenografts.
AB  - We have developed unique replication-competent retroviral (RCR) vectors based on
      murine leukemia virus that provide improved efficiency of viral delivery, allow
      for long-term transgene expression and demonstrate an intrinsic selectivity for
      transduction of rapidly dividing tumor cells. The purpose of this study was to
      evaluate the in vivo transduction efficiency and the therapeutic efficacy of the
      RCR vector mediated delivery of Escherichia coli purine nucleoside phosphorylase
      (PNP) in combination with fludarabine phosphate for bladder cancer. We
      constructed vectors containing green fluorescent protein (GFP) gene (ACE)-GFP) or
      PNP gene (ACE-PNP). KU-19-19 bladder tumors exhibited 28.3+/-16.1, 46.6+/-5.8 and
      93.7+/-7.8% of GFP expression on 14, 18 and 26 days after intratumoral injection
      of ACE-GFP, respectively. GFP expression could not be observed in normal tissues
      surrounding the injected tumors. No detectable polymerase chain reaction products
      of GFP gene could be observed in any distant organs. Intratumoral injection of
      ACE-PNP, followed by systemically administered fludarabine phosphate,
      significantly inhibited the growth of pre-established KU-19-19 tumors. Our
      results indicate that RCR vectors are a potentially efficient gene delivery
      method and that the RCR vector mediated PNP gene transfer and fludarabine
      phosphate treatment might be a novel and potentially therapeutic modality for
      bladder cancer.

PMID- 17218951
TI  - The tumour microenvironment as a target for chemoprevention.
AB  - New data indicate that primary dysfunction in the tumour microenvironment, in
      addition to epithelial dysfunction, can be crucial for carcinogenesis. These
      recent findings make a compelling case for targeting the microenvironment for
      cancer chemoprevention. We review new insights into the pathophysiology of the
      microenvironment and new approaches to control it with chemopreventive agents.
      The microenvironment of a cancer is an integral part of its anatomy and
      physiology, and functionally, one cannot totally dissociate this microenvironment
      from what have traditionally been called 'cancer cells'. Finally, we make
      suggestions for more effective clinical implementation of this knowledge in
      preventive strategies.

PMID- 17218952
TI  - Ischaemic brain damage after stroke: new insights into efficient therapeutic
      strategies. International Symposium on Neurodegeneration and Neuroprotection.

PMID- 17218953
TI  - Escherichia coli with a linear genome.
AB  - Chromosomes in eukaryotes are linear, whereas those of most, but not all,
      prokaryotes are circular. To explore the effects of possessing a linear genome on
      prokaryotic cells, we linearized the Escherichia coli genome using the lysogenic
      lambda-like phage N15. Linear genome E. coli were viable and their genome
      structure was stable. There were no appreciable differences between cells with
      linear or circular genomes in growth rates, cell and nucleoid morphologies,
      genome-wide gene expression (with a few exceptions), and DNA gyrase- and
      topoisomerase IV-dependent growth. However, under dif-defective conditions, only
      cells with a circular genome developed an abnormal phenotype. Microscopy
      indicated that the ends of the linear genome, but not the circular genome, were
      separated and located at each end of a new-born cell. When tos - the cis-element
      required for linearization - was inserted into different chromosomal sites, those
      strains with the genome termini that were more remote from dif showed greater
      growth deficiencies.

PMID- 17218954
TI  - Translational repression of E2F1 mRNA in carcinoma in situ and normal testis
      correlates with expression of the miR-17-92 cluster.

PMID- 17218955
TI  - Endoplasmic reticulum stress-induced apoptosis requires bax for commitment and
      Apaf-1 for execution in primary neurons.
AB  - Apoptosis triggered by endoplasmic reticulum (ER) stress is associated with
      various pathophysiological conditions including neurodegenerative diseases and
      ischemia. However, the mechanism by which ER stress induces neuronal apoptosis
      remains controversial. Here we identify the pathway of apoptosis carried out in
      sympathetic neurons triggered to die by ER stress-inducing agent tunicamycin. We
      find that ER stress induces a neuronal apoptotic pathway which upregulates BH3
      only genes DP5 and Puma. Importantly, we show that ER stress commits neurons to
      die before cytochrome c release and this commitment requires Bax activation and c
      jun N-terminal kinase signaling. Furthermore, ER stress engages the mitochondrial
      pathway of death as neurons release cytochrome c and Apaf-1 deficiency is
      sufficient to block apoptosis. Our findings identify a critical function of Bax
      in committing neurons to ER stress-induced apoptosis and clarify the importance
      of the apoptosome as the non-redundant caspase activation pathway to execute
      neuronal apoptosis in response to ER stress.

PMID- 17218956
TI  - c-Jun N-terminal kinase mediates hydrogen peroxide-induced cell death via
      sustained poly(ADP-ribose) polymerase-1 activation.
AB  - Reactive oxygen species (ROS) have been closely associated with both apoptotic
      and non-apoptotic/necrotic cell death. Our previous study has illustrated that c
      Jun-N-terminal kinase 1 (JNK1) is the main executor in hydrogen peroxide
      (H(2)O(2))-induced nonapoptotic cell death. The main objective of this study is
      to further elucidate the molecular mechanisms downstream of JNK1 in H(2)O(2)
      induced cell death. In this study, poly(ADP-ribose) polymerase-1 (PARP-1), a key
      DNA repair protein, was readily activated by H(2)O(2) and inhibition of PARP-1
      activation by either a pharmacological or genetic approach offered significant
      protection against H(2)O(2)-induced cell death. More importantly, H(2)O(2)
      mediated PARP-1 activation is subject to regulation by JNK1. Suppression of JNK1
      activation by a chemical inhibitor or genetic deletion markedly suppressed the
      late-phase PARP-1 activation induced by H(2)O(2), suggesting that JNK1
      contributes to the sustained activation of PARP-1. Such findings were supported
      by the temporal pattern of nuclear translocation of activated JNK and a direct
      protein-protein interaction between JNK1 and PARP-1 in H(2)O(2)-treated cells.
      Finally, in vitro kinase assay suggests that PARP-1 may serve as the direct
      phosphorylation target for JNK1. Taken together, data from our study reveal a
      novel underlying mechanism in H(2)O(2)-induced nonapoptotic cell death: JNK1
      promotes a sustained PARP-1 activation via nuclear translocation, protein-protein
      interaction and PARP-1 phosphorylation.

PMID- 17218957
TI  - Cyclin-dependent kinase 5 is an upstream regulator of mitochondrial fission
      during neuronal apoptosis.
AB  - Under physiological conditions, mitochondrial morphology dynamically shifts
      between a punctuate appearance and tubular networks. However, little is known
      about upstream signal transduction pathways that regulate mitochondrial
      morphology. We show that mitochondrial fission is a very early and kinetically
      invariant event during neuronal cell death, which causally contributes to
      cytochrome c release and neuronal apoptosis. Using a small molecule CDK5
      inhibitor, as well as a dominant-negative CDK5 mutant and RNAi knockdown
      experiments, we identified CDK5 as an upstream signalling kinase that regulates
      mitochondrial fission during apoptosis of neurons. Vice versa, our study shows
      that mitochondrial fission is a modulator contributing to CDK5-mediated
      neurotoxicity. Thereby, we provide a link that allows integration of CDK5 into
      established neuronal apoptosis pathways.

PMID- 17218958
TI  - Stage-specific expression of DNasegamma during B-cell development and its role in
      B-cell receptor-mediated apoptosis in WEHI-231 cells.
AB  - Here, we describe the non-redundant roles of caspase-activated DNase (CAD) and
      DNasegamma during apoptosis in the immature B-cell line WEHI-231. These cells
      induce DNA-ladder formation and nuclear fragmentation by activating CAD during
      cytotoxic drug-induced apoptosis. Moreover, these apoptotic manifestations are
      accompanied by inhibitor of CAD (ICAD) cleavage and are abrogated by the
      constitutive expression of a caspase-resistant ICAD mutant. No such nuclear
      changes occur during oxidative stress-induced necrosis, indicating that neither
      CAD nor DNasegamma functions under necrotic conditions. Interestingly, the DNA
      ladder formation and nuclear fragmentation induced by B-cell receptor ligation
      occur in the absence of ICAD cleavage and are not significantly affected by the
      ICAD mutant. Both types of nuclear changes are preceded by the upregulation of
      DNasegamma expression and are strongly suppressed by 4-(4,6-dichloro-[1, 3, 5]
      triazin-2-ylamino)-2-(6-hydroxy-3-oxo-3H-xanthen-9-yl)-benzoic acid (DR396),
      which is a specific inhibitor of DNasegamma. Our results suggest that DNasegamma
      provides an alternative mechanism for inducing nuclear changes when the working
      apoptotic cascade is unsuitable for CAD activation.

PMID- 17218959
TI  - Essential postmitochondrial function of p53 uncovered in DNA damage-induced
      apoptosis in neurons.
AB  - In postmitotic sympathetic neurons, unlike most mitotic cells, death by apoptosis
      requires not only the release of cytochrome c from the mitochondria, but also an
      additional step to relieve X-linked inhibitor of apoptosis protein (XIAP)'s
      inhibition of caspases. Here, we examined the mechanism by which XIAP is
      inactivated following DNA damage and found that it is achieved by a mechanism
      completely different from that following apoptosis by nerve growth factor (NGF)
      deprivation. NGF deprivation relieves XIAP by selectively degrading it, whereas
      DNA damage overcomes XIAP via a p53-mediated induction of Apaf-1. Unlike wild
      type neurons, p53-deficient neurons fail to overcome XIAP and remain resistant to
      cytochrome c after DNA damage. Restoring Apaf-1 induction in p53-deficient
      neurons is sufficient to overcome XIAP and sensitize cells to cytochrome c.
      Although a role for p53 in apoptosis upstream of cytochrome c release has been
      well established, this study uncovers an additional, essential role for p53 in
      regulating caspase activation downstream of mitochondria following DNA damage in
      neurons.

PMID- 17218960
TI  - Structural and functional analyses of the wheat genomes based on expressed
      sequence tags (ESTs) related to abiotic stresses.
AB  - To gain insights into the structure and function of the wheat (Triticum aestivum
      L.) genomes, we identified 278 ESTs related to abiotic stress (cold, heat,
      drought, salinity, and aluminum) from 7671 ESTs previously mapped to wheat
      chromosomes. Of the 278 abiotic stress related ESTs, 259 (811 loci) were assigned
      to chromosome deletion bins and analyzed for their distribution pattern among the
      7 homoeologous chromosome groups. Distribution of abiotic stress related EST loci
      were not uniform throughout the different regions of the chromosomes of the 3
      wheat genomes. Both the short and long arms of group 4 chromosomes showed a
      higher number of loci in their distal regions compared with proximal regions. Of
      the 811 loci, the number of mapped loci on the A, B, and D genomes were 258, 281,
      and 272, respectively. The highest number of abiotic stress related loci were
      found in homoeologous chromosome group 2 (142 loci) and the lowest number were
      found in group 6 (94 loci). When considering the genome-specific ESTs, the B
      genome showed the highest number of unique ESTs (7 loci), while none were found
      in the D genome. Similarly, considering homoeologous group-specific ESTs, group 2
      showed the highest number with 16 unique ESTs (58 loci), followed by group 4 with
      9 unique ESTs (33 loci). Many of the classified proteins fell into the biological
      process categories associated with metabolism, cell growth, and cell maintenance.
      Most of the mapped ESTs fell into the category of enzyme activity (28%), followed
      by binding activity (27%). Enzymes related to abiotic stress such as beta
      galactosidase, peroxidase, glutathione reductase, and trehalose-6-phosphate
      synthase were identified. The comparison of stress-responsive ESTs with genomic
      sequences of rice (Oryza sativa L.) chromosomes revealed the complexities of
      colinearity. This bin map provides insight into the structural and functional
      details of wheat genomic regions in relation to abiotic stress.

PMID- 17218961
TI  - Induction of apoptosis in K562 cells by jolkinolide B.
AB  - Jolkinolide B, a bioactive diterpene isolated from the roots of Euphorbia
      fischeriana Steud, has various biological and pharmacological properties. In this
      study, the cytotoxicity of highly purified jolkinolide B was tested in human
      chronic myeloid leukemia (K562) and 2 other cell lines (human esophageal
      carcinoma Eca-109 and human hepatoma HepG2). The results indicate a significant
      decrease in the proliferation of all the 3 cell lines when treated with
      jolkinolide B for 24 h; the IC50 value of cytotoxicity was 12.1 microg/mL (for
      K562 cells), >50.0 microg/mL (for HepG2 cells), and 23.7 microg/mL (for Eca-109
      cells). Further study of K562 cells involving fluorescence and transmission
      electron microscopy revealed characteristic apoptotic features, such as cell
      shrinkage, membrane blebbing, loss of microvilli, and nuclear condensation.
      Agarose electrophoresis of genomic DNA showed a typical fragmentation pattern for
      apoptotic cells. A kinetic cell-cycle analysis demonstrated that the cell cycle
      was arrested in the G1 phase. All these results suggest that the anti
      proliferation effect of jolkinolide B on K562 cells is achieved by arresting the
      cell cycle in the G1 phase and subsequently inducing apoptosis.

PMID- 17218962
TI  - Anti-fibrotic effects of tetrandrine on bile-duct ligated rats.
AB  - Tetrandrine (Tet) (C38H42O8N2; molecular weight, 622), an alkaloid isolated from
      the Chinese medicinal herb Stephania tetrandra, has been shown to elicit anti
      inflammatory and anti-fibrotic effects in pulmonary diseases, but the mechanism
      of action has yet to be investigated. In this study, we tested whether Tet exerts
      anti-fibrotic effects on rat hepatic fibrosis through anti-NFkappaB pathways.
      After bile-duct ligation, rats were given Tet (1 or 5 mg/kg) or silymarin (50
      mg/kg, as a positive control) by gavage twice daily for 3 weeks. Liver sections
      were taken for Sirius red quantitative scoring, immunofluorescence double
      staining of alpha-smooth muscle actin (alpha-SMA) and NFkappaB, and for
      quantitative determinations of the mRNA expression levels of TGF-beta1, alpha
      SMA, collagen 1alpha2, inducible nitric oxide synthase (iNOS), intercellular
      adhesion molecule 1 (ICAM-1), metallothionein, vascular endothelial growth factor
      (VEGF), and VEGF type II receptor (VEGFR2) genes. The results showed that both
      Tet and silymarin treatment significantly reduced the fibrosis scores and hepatic
      collagen content of BDL rats, compared with no treatment. Both Tet and silymarin
      treatments decreased the number of alpha-SMA- and NFkappaB-positive cells in
      fibrotic livers. Moreover, Tet and silymarin treatments attenuated the mRNA
      expression levels of TGF-beta1,alpha-SMA, collagen 1alpha2, iNOS, ICAM-1, VEGF,
      and VEGFR2 genes, and induced the mRNA expression of the metallothionein gene.
      This study suggests that the anti-fibrotic effects of Tet were related to the
      reduction of fibrosis-related gene transcription, the attenuation of NFkappaB
      activated pathways, and the induction of metallothionein gene transcription in
      the livers of BDL rats.

PMID- 17218963
TI  - Effect of stress on hepatic 11beta-hydroxysteroid dehydrogenase activity and its
      influence on carbohydrate metabolism.
AB  - Stress activates the synthesis and secretion of catecholamines and adrenal
      glucocorticoids, increasing their circulating levels. In vivo, hepatic 11beta
      hydroxysteroid dehydrogenase 1 (HSD1) stimulates the shift of 11
      dehydrocorticosterone to corticosterone, enhancing active glucocorticoids at
      tissue level. We studied the effect of 3 types of stress, 1 induced by
      bucogastric overload with 200 mmol/L HCl causing metabolic acidosis (HCl), the
      second induced by bucogastric overload with 0.45% NaCl (NaCl), and the third
      induced by simulated overload (cannula), on the kinetics of hepatic HSD1 of rats
      and their influence on the activity of the gluconeogenic enzyme
      phosphoenolpyruvate carboxykinase, glycemia, and glycogen deposition. Compared
      with unstressed controls, all types of stress significantly increased HSD1
      activity (146% cannula, 130% NaCl, and 253% HCl), phosphoenolpyruvate
      carboxykinase activity (51% cannula, 48% NaCl, and 86% HCl), and glycemia (29%
      cannula, 30% NaCl, and 41% HCl), but decreased hepatic glycogen (68% cannula, 68%
      NaCl, and 78% HCl). Owing to these results, we suggest the following events occur
      when stress is induced: an increase in hepatic HSD1 activity, augmented active
      glucocorticoid levels, increased gluconeogenesis, and glycemia. Also involved are
      the multiple events indirectly related to glucocorticoids, which lead to the
      depletion of hepatic glycogen deposits, thereby contributing to increased
      glycemia. This new approach shows that stress increments the activity of hepatic
      HSD1 and suggests that this enzyme could be involved in the development of the
      Metabolic Syndrome.

PMID- 17218964
TI  - Effects of sympathetic stimulation during cooling on hypothermic as well as
      posthypothermic hemodynamic function.
AB  - This experimental study was performed to explore hemodynamic effects of a
      moderate dose epinephrine (Epi) during hypothermia and to test the hypothesis
      whether sympathetic stimulation during cooling affects myocardial function
      following rewarming. Two groups of male Wistar rats (each, n=7) were cooled to 15
      degrees C, maintained at this temperature for 1 h, and then rewarmed. Group 1
      received 1 microg/min Epi, i.v., for 1 h during cooling to 28 degrees C, a dose
      known to elevate cardiac output (CO) by approximately 25% at 37 degrees C. Group
      2 served a saline solution control. At 37 degrees C, Epi infusion elevated CO,
      left ventricular systolic pressure, maximum rate of left ventricle pressure rise,
      and mean arterial pressure. During cooling to 28 degrees C, these variables, with
      the exception of mean arterial pressure, decreased in parallel to those in the
      saline solution group. In contrast, in the Epi group, mean arterial pressure
      remained increased and total peripheral resistance was significantly elevated at
      28 degrees C. Compared with corresponding prehypothermic values, most hemodynamic
      variables were lowered after 1 h at 15 degrees C in both groups (except for
      stroke volume). After rewarming, alterations in hemodynamic variables in the Epi
      treated group were more prominent than in saline solution controls. Thus, before
      cooling, continuous Epi infusion predominantly stimulates myocardial mechanical
      function, materialized as elevation of CO, left ventricular systolic pressure,
      and maximum rate of left ventricle pressure rise. Cooling, on the other hand,
      apparently eradicates central hemodynamic effects of Epi and during stable
      hypothermia, elevation of peripheral vascular vasopressor effects seem to take
      over. In contrast to temperature-matched, non-Epi stimulated control rats, a
      significant depression of myocardial mechanical function occurs during rewarming
      following a moderate sympathetic stimulus during initial cooling.

PMID- 17218965
TI  - Enhanced trabecular-bone calcium deposition in female rats with a high
      physiological dose of prolactin diminishes after ovariectomy.
AB  - Although an increase in trabecular-bone calcium deposition has been shown to be
      regulated by prolactin during lactation, the physiological significance of
      prolactin in bone calcium metabolism in nonlactating rats remains unclear. This
      investigation sought to demonstrate the effects of endogenous prolactin and a
      high physiological dose of exogenous prolactin on bone turnover and bone calcium
      deposition in normal female rats, using the 45Ca-labeling technique. Our results
      showed that suppression of endogenous prolactin with 6 mg/kg bromocriptine for 15
      days significantly enhanced bone formation, but not bone resorption, in primarily
      trabecular sites, resulting in a significant increase in calcium deposition in
      the sternum and vertebrae, from -0.20+/-0.07 to 0.40+/-0.09 (p<0.05) and -0.07+/
      0.11 to 0.34+/-0.06 (p<0.05) mmol Ca.(g dry mass)-1, respectively. Similarly, 2.5
      mg/kg prolactin, a high physiological dose, increased sternal and vertebral
      calcium deposition, from -0.20+/-0.07 to 0.24+/-0.09 (p<0.05) and -0.07+/-0.11 to
      0.25+/-0.18 (p<0.05) mmol Ca.(g dry mass)-1, respectively, by increasing bone
      formation more than bone resorption. However, as expected, prolactin had no
      effect on the tibia or femur, which are primarily cortical sites. Because several
      actions of prolactin have been known to be estradiol-dependent, we further
      investigated the dependence of prolactin action on 17beta-estradiol. We found
      that 2.5 mg/kg prolactin did not increase sternal calcium deposition in
      ovariectomized rats. However, 10 microg/kg 17beta-estradiol supplementation
      restored the action of prolactin. Ovariectomized rats given 17beta-estradiol plus
      prolactin also manifested slightly but significantly higher sternal total calcium
      content than sham-operated rats, (4.58+/-0.12 vs. 4.36+/-0.11 mmol Ca.(g dry
      mass)-1 (p<0.05)). We concluded that a high physiological dose of prolactin
      promoted calcium deposition in primarily trabecular sites of nonlactating rats.
      This effect was diminished after ovariectomy. In addition, we showed that basal
      endogenous prolactin played a role in the maintenance of normal trabecular-bone
      turnover.

PMID- 17218966
TI  - Effect of uroguanylin on potassium and bicarbonate transport in rat renal
      tubules.
AB  - The effect of uroguanylin (UGN) on K+ and H+ secretion in the renal tubules of
      the rat kidney was studied using in vivo stationary microperfusion. For the study
      of K+ secretion, a tubule was punctured to inject a column of FDC-green-colored
      Ringer's solution with 0.5 mmol KCl/L+/-10(-6) mol UGN/L, and oil was used to
      block fluid flow. K+ activity and transepithelial potential differences (PD) were
      measured with double microelectrodes (K+ ion-selective resin vs. reference) in
      the distal tubules of the same nephron. During perfusion, K+ activity rose
      exponentially, from 0.5 mmol/L to stationary concentration, allowing for the
      calculation of K+ secretion (JK). JK increased from 0.63+/-0.06 nmol.cm-2.s-1 in
      the control group to 0.85+/-0.06 in the UGN group (p<0.01). PD was -51.0+/-5.3 mV
      in the control group and -50.3+/-4.98 mV in the UGN group. In the presence of 10(
      7) mol iberiotoxin/L, the UGN effect was abolished: JK was 0.37+/-0.038 nmol.cm
      2.s-1 in the absence of, and 0.38+/-0.025 in the presence of, UGN, indicating its
      action on maxi-K channels. In another series of experiments, renal tubule
      acidification was studied, using a similar method: proximal and distal tubules
      were perfused with solutions containing 25 mmol NaHCO3/L. Acidification half-time
      was increased both in proximal and distal segments and, as a consequence,
      bicarbonate reabsorption decreased in the presence of UGN (in proximal tubules,
      from 2.40+/-0.26 to 1.56+/-0.21 nmol.cm-2.s-1). When the Na+/H+ exchanger was
      inhibited by 10(-4) mol hexamethylene amiloride (HMA)/L, the control and UGN
      groups were not significantly different. In the late distal tubule, after HMA,
      UGN significantly reduced JHCO3-, indicating an effect of UGN on H+-ATPase. These
      data show that UGN stimulated JK+ by acting on maxi-K channels, and decreased
      JHCO3- by acting on NHE3 in proximal and H+-ATPase in distal tubules.

PMID- 17218967
TI  - Expression of gap junctional connexins 26, 32, and 43 mRNA in ovarian
      preovulatory follicles and corpora lutea in sheep.
AB  - The objective of the current study was to evaluate the expression of connexins
      (Cx)26, Cx32, and Cx43 mRNA in granulosa and theca cells during the peri
      ovulatory period (experiment 1) and in the corpus luteum (CL) during the estrous
      cycle (experiment 2) and during prostaglandin F2alpha (PGF)-induced luteal
      regression (experiment 3) in FSH-treated ewes. In experiment 1, Cx26, Cx32, and
      Cx43 mRNA was expressed in granulosa and theca cells, and expression of Cx32 and
      Cx43 mRNA, but not Cx26, was greater (p<0.001) in granulosa than in theca cells
      throughout the peri-ovulatory period. Expression of Cx43 mRNA in granulosa and
      theca cells decreased (p<0.01) 24 h after hCG treatment. In experiment 2,
      expression of Cx26 mRNA in the CL tended to be greater (p<0.06) on day 10 than on
      days 5 or 15, but expression of Cx43 mRNA was greater (p<0.01) on day 5 than on
      days 10 and 15 of the estrous cycle. In experiment 3, expression of Cx26, but not
      Cx32 or Cx43 mRNA decreased (p<0.001) during PGF-induced luteal regression. In
      all 3 experiments, expression of Cx32 mRNA was much less than Cx26 and Cx43 mRNA.
      Moreover, Cx32 mRNA expression was unchanged during the peri-ovulatory period or
      during several stages of luteal development and PGF-induced regression of the CL.
      Thus, we have shown that the mRNA expression pattern of Cx26 and Cx43 changes
      during peri-ovulatory period and during several stages of the luteal development.
      This suggests that Cx26 and Cx43 play a role in ovarian tissue remodeling during
      the critical time around ovulation and throughout luteal tissue growth,
      differentiation, and regression in sheep.

PMID- 17218968
TI  - Assessment of supra-additive effects of cytotoxic drugs and low dose rate
      irradiation in an in vitro model for hepatocellular carcinoma.
AB  - The use of 5-fluorouracil, topotecan, or gemcitabine was tested for enhancement
      of the effects of low dose rate (LDR) irradiation in an in vitro model for
      hepatocellular carcinoma. For comparison, all drugs were tested in combination
      with high dose rate (HDR) gamma-irradiation as well. Multicellular spheroids of
      HepG2 cells were exposed to HDR or LDR irradiation by means of external beam
      cobalt-60 or rhenium-188 (188Re), respectively, dissolved in the culture medium.
      Secondly, exposure to irradiation was combined with the cytotoxic drug. Toxicity
      was evaluated by means of a quantitative spheroid outgrowth assay and histology.
      For 5-fluorouracil, supra-additive effects were observed in combination with HDR
      irradiation. With 188Re, the supra-additive toxicity was only transient. For
      topotecan and 188Re, no supra-additive effects were seen, whereas the addition of
      HDR irradiation at the end of the topotecan exposure yielded lasting supra
      additive effects. Incubation with gemcitabine followed by exposure to HDR
      irradiation, induced a synergistic toxicity on the outgrowth. No supra-additive
      effects were observed when HDR irradiation was added at the start of the
      incubation with gemcitabine or combined with LDR irradiation. For all drugs
      tested, supra-additive effects were observed with HDR irradiation if the timing
      of the irradiation was appropriate. For 188Re, no lasting supra-additive effects
      were observed.

PMID- 17218969
TI  - Enhanced Ca2+ sensitivity in hyperresponsive cultured bronchi is mediated by
      TNFalpha and NF-kappaB.
AB  - The mechanical properties and Ca2+ sensitivity of an organ-culture model derived
      from guinea pig airways have been examined. The cultured explants develop airway
      hyperresponsiveness to pharmacological agonists after 3-day culture, when
      compared with fresh and ovalbumin-sensitized tissues. The reactivity of cultured
      explants is dependent on the presence of the epithelium. They are also sensitive
      to glucocorticosteroid pretreatments, which neutralize the TNFalpha antibody and
      NF-kappaB inhibitor. Hence, specific immunostaining of NF-kappaB subunits (p65
      and p50) was increased in the nuclear extract of cultured explants. In beta-escin
      permeabilized preparations, step-increases in pCa revealed enhanced Ca2+
      sensitivity of the contractile apparatus in cultured explants, which was
      prevented by epithelium removal. Pretreatments of cultured explants with
      neutralizing TNFalpha antibody and NF-kappaB inhibitor consistently reduced their
      Ca2+ sensitivity. These findings suggest that AHR developed in this organ culture
      model may be triggered by an inflammatory process mediated by the TNFalpha and NF
      kappaB transcription factor, which results in an increased sensitivity to
      [Ca2+]i.

PMID- 17218970
TI  - The role of caspase-3 in lipopolysaccharide-mediated disruption of intestinal
      epithelial tight junctions.
AB  - The mechanisms responsible for microbially induced epithelial apoptosis and
      increased intestinal permeability remain unclear. This study assessed whether
      purified bacterial lipopolysaccharide (LPS) increases epithelial apoptosis and
      permeability and whether these changes are dependent on caspase-3 activation. In
      nontumorigenic epithelial monolayers, Escherichia coli O26:B6 LPS increased
      apoptosis, as shown by nuclear breakdown, caspase-3 activation, and PARP
      cleavage, and induced disruption of tight junctional ZO-1. Apical, but not
      basolateral, exposure to LPS increased epithelial permeability. Addition of a
      caspase-3 inhibitor abolished the effects of LPS. The findings describe a novel
      mechanism whereby apical LPS may disrupt epithelial tight junctional ZO-1 and
      barrier function in a caspase-3-dependent fashion.

PMID- 17218971
TI  - Role of 15-hydroxyeicosatetraenoic acid in phosphorylation of ERK1/2 and
      caldesmon in pulmonary arterial smooth muscle cells.
AB  - We have reported that 15-hydroxyeicosatetraenoic acid (15-HETE) induces pulmonary
      artery (PA) contraction in rats exposed to hypoxia by activating extracellular
      signal-regulated kinase 1/2 (ERK1/2). In this study, we investigated the
      characteristics of 15-HETE mediating phosphorylation of ERK1/2 and caldesmon in
      rat pulmonary arterial smooth muscle cells (PASMCs). Our data showed that 15-HETE
      upregulated ERK1/2 phosphorylation in a dose-dependent manner, which could be
      blocked by ERK pathway inhibitors U0126 and PD98059. ERK1/2 phosphorylation was
      attenuated by inhibiting endogenous 15-HETE formation with lipoxygenase
      inhibitor, cinnamyl 3,4-dihydroxy-[alpha]-cyanocinnamate (CDC), in both normoxic
      and hypoxic PASMCs. ERK1/2 phosphorylation in response to 15-HETE was detected in
      cytosol as well as in nucleus and phosphorylatd ERK1/2 partly translocated into
      nucleus, which could be blocked by PD98059. In addition, caldesmon was
      phosphorylated in 15-HETE-stimulated cells; this could be inhibited by PD98059.
      These data demonstrated that 15-HETE is associated with ERK1/2 activation and
      caldesmon phosphorylation in PASMCs and that 15-HETE is at least partly involved
      in mediating activation of hypoxia-initiated ERK pathway, possibly leading to
      hypoxic pulmonary vasoconstriction.

PMID- 17218972
TI  - Protective effects of polysaccharide from Euphorbia kansui (Euphorbiaceae) on the
      swimming exercise-induced oxidative stress in mice.
AB  - The present study examined the effects of derivatives of galactosides and
      glucosides in a polysaccharide extract from Euphorbia kansui (Euphorbiaceae) on
      exercise-induced oxidative stress in mice. Exhaustive swimming exercise
      significantly increases the degree of lipid peroxidation in terms of
      malondialdehyde content and reduces the antioxidant activities of superoxide
      dismutase (SOD) and glutathione peroxidase (GPx). Our findings revealed that
      chronic oral treatment with the extract elevates enzymatic activities of SOD and
      GPx accompanied by a corresponding decrease in malondialdehyde. The antioxidative
      activities of these compounds against exercise-induced oxidative stress are
      correlated with various activities such as reducing the production of superoxide
      and hydroxyl radicals, inhibiting lipid peroxidation, enhancing antioxidative
      defenses, and increasing the production of SOD and GPx activity and expression in
      different tissues. These compounds may be involved in glycogen metabolism to meet
      the requirement of working skeletal muscles and act as antioxidants by
      terminating the chain reaction of lipid peroxidation to maintain the
      morphological stability of mitochondria in spinal motor neurons. These
      observations suggest that E. kansui has antioxidative and antifatigue properties
      and can be given as prophylactic and (or) therapeutic supplements for increasing
      antioxidant enzyme activities and preventing lipid peroxidation during strenuous
      exercise.

PMID- 17218973
TI  - Physiological role and regulation of the Na+/H+ exchanger.
AB  - In mammalian eukaryotic cells, the Na+/H+ exchanger is a family of membrane
      proteins that regulates ions fluxes across membranes. Plasma membrane isoforms of
      this protein extrude 1 intracellular proton in exchange for 1 extracellular
      sodium. The family of Na+/H+ exchangers (NHEs) consists of 9 known isoforms, NHE1
      NHE9. The NHE1 isoform was the first discovered, is the best characterized, and
      exists on the plasma membrane of all mammalian cells. It contains an N-terminal
      500 amino acid membrane domain that transports ions, plus a 315 amino acid C
      terminal, the intracellular regulatory domain. The Na+/H+ exchanger is regulated
      by both post-translational modifications including protein kinase-mediated
      phosphorylation, plus by a number of regulatory-binding proteins including
      phosphatidylinositol-4,5-bisphosphate, calcineurin homologous protein, ezrin,
      radixin and moesin, calmodulin, carbonic anhydrase II, and tescalcin. The Na+/H+
      exchanger is involved in a variety of complex physiological and pathological
      events that include regulation of intracellular pH, cell movement, heart disease,
      and cancer. This review summarizes recent advances in the understanding of the
      physiological role and regulation of this protein.

PMID- 17218974
TI  - Field stimulation-induced tetrodotoxin-resistant vasorelaxation is mediated by
      sodium hypochlorite.
AB  - This study was done to determine the mechanism of field stimulation-induced
      tetrodotoxin (TTX)- and NG- nitro-l-arginine (LNA)-resistant vasorelaxation.
      Field stimulation with platinum and carbon, but not with silver, electrodes (30
      V, 30 HZ, 2-5 ms pulse width) as well as electrically stimulated salt (0.9% NaCl)
      solution (ESSS) or Krebs solution caused 100% relaxation of phenylephrine
      contracted rat aortic strips, which was TTX and LNA resistant and endothelium
      independent. ESSS also relaxed other vascular preparations (rabbit aorta and
      renal artery, dog coronary artery, pig ductus arteriosus, and rat portal vein).
      The electric current generated hypochlorite (OCl-) and H2O2 from the salt
      solution; however, vasorelaxation was caused by NaOCl and not by H2O2. ESSS and
      NaOCl caused contraction failure of spontaneously beating right atria of rats and
      did not affect uterine contractions, vascular cAMP, cGMP, or the pH of the tissue
      bath. Field stimulation, ESSS, and NaOCl did not relax aortic preparations
      contracted by 32 mmol/L potassium and their vasorelaxant effects on phenylephrine
      contracted rat aortic strips and rings were completely reversed by
      tetraethylammonium and partially by glibenclamide and iberiotoxin. We conclude
      that electric pulses generate the oxidant OCl- from the salt solution, which
      causes vasorelaxation by increasing K+ conductance.

PMID- 17218975
TI  - Inhibition of human and rabbit arterial smooth muscle cell migration mediated by
      the kinin B1 receptor: role of receptor density and released mediators.
AB  - Bradykinin (BK)-related peptides are suspected to negatively influence diverse
      functions in vascular smooth muscle cells (SMCs), notably via stimulation of the
      inducible B1 receptor (B1R), and have been shown to inhibit the migration of rat
      SMCs. The present study had several objectives: (i) to test whether B1R mediates
      the inhibition of migration of arterial SMCs from additional species (the human
      and the rabbit); (ii) whether B1R density influences this action and whether
      autocrine NO or prostanoid release modulate it; and (iii) the possible signaling
      interaction between the B1R and phosphatidylinositol-3 kinase (PI-3K) has been
      addressed. The peptidase resistant B1R agonist Sar-[D-Phe8]des-Arg9-BK (10 nmol/L
      - 1 micromol/L) was an inhibitor of migration in human or rabbit arterial SMCs in
      a wound closure assay, more effectively if the medium composition allowed a high
      B1R expression (20% fetal bovine serum (FBS) + interleukin-1beta (IL-1beta) in
      human SMCs, 10% FBS in rabbit cells). The effect of the B1R agonist on motility
      was abrogated by a B1R antagonist, B-9858, but not by the B2R antagonist Hoe 140;
      a peptidase-resistant B2R agonist, [Phe8Psi(CH2-NH)-Arg9]BK, had a marginal or no
      effect on migration. Sar-[D-Phe8]des-Arg9-BK (1 micromol/L) did not significantly
      influence SMC proliferation. The B1R-mediated inhibition of SMC migration was not
      affected by pharmacological inhibition of the nitric oxide synthases or
      cyclooxygenases-1 or -2, but was correlated to an inhibition of PI-3K in both
      types of SMCs. The inhibition of SMC migration mediated by the kinin B1R is
      likely independent from NO or prostanoid release, applicable to several species,
      and correlated to receptor density and the inhibition of PI-3K.

PMID- 17218976
TI  - Characterization of the vasorelaxation to methanandamide in rat gastric arteries.
AB  - In the present study, the relaxant effect of the cannabinoid methanandamide was
      explored in rat gastric arteries. Since in some vessels cannabinoids have been
      shown to release calcitonin gene-related peptide (CGRP) from perivascular nerves,
      the influence of methanandamide was compared with that of exogenous CGRP.
      Methanandamide and CGRP elicited concentration-dependent, endothelium-independent
      relaxations. Methanandamide-induced relaxations were unaffected by the CB1
      receptor antagonist AM251, the CB2 receptor antagonists AM630 and SR144528, and
      combined pre-exposure to AM251 and SR144528. Pre-exposure to O-1918, an
      antagonist of a novel nonCB1/nonCB2 cannabinoid receptor, did not influence the
      relaxations to methanandamide. Capsaicin or capsazepine treatment slightly
      inhibited methanandamide-induced relaxations. Preincubation with 30 mmol/L
      extracellular K+ or 3 mmol/L TEA had no significant effect on the responses
      elicited by methanandamide, but reduced CGRP-induced relaxations. Relaxation to
      10(-5) mol/L methanandamide was significantly blunted by Bay K8644 and by
      preincubation with nifedipine. Furthermore, 10(-5) mol/L methanandamide
      significantly inhibited CaCl2-induced contractions in norepinephrine-stimulated
      vessels previously depleted of intra- and extracellular Ca2+. Finally,
      preincubation with 10(-5) mol/L methanandamide almost completely abolished high
      K+-induced contractions. These findings suggest that the vasorelaxant action of
      methanandamide in rat gastric arteries is not mediated by stimulation of known
      cannabinoid receptors and only partly related to stimulation of TRPV1 receptors
      on perivascular nerves. At high concentrations, methanandamide might induce
      relaxation by reducing calcium entry into the smooth muscle cells.

PMID- 17218977
TI  - Calcium-independent tacrine-induced relaxation of rat gastric corpus smooth
      muscles.
AB  - Tacrine, a non-competitive reversible acetylcholinesterase and
      butyrylcholineserase inhibitor, caused a concentration-dependent tonic
      contraction of gastric smooth muscle preparations in the concentration range 1 x
      10(-7) mol/L - 1 x 10(-5) mol/L, whereas concentrations higher than 2 x 10(-5)
      mol/L induced a biphasic effect; a short-time contraction was followed by a
      prolonged relaxation. To shed some light on the mechanism underlying this
      untypical relaxation, the amplitude of mechanical reactions caused by tacrine
      were compared with those of tacrine in the presence of atropine, ipratropium,
      metrifonate, TTX, nifedipine, D-600, caffeine, apamin, and charybdotoxin. The
      results obtained revealed that the relaxation was neither cholinergic in nature,
      nor mediated by the influence of the drug on intramural neuronal structures. It
      was not influenced by processes inducing changes in cytosolic Ca2+ levels. This
      assumption was confirmed by experiments with permeabilized muscle preparations
      that were pre-contracted in a solution with pCa 5.5. Tacrine relaxed the smooth
      muscles in spite of the constant intracellular Ca2+ concentration resulting from
      the permeabilization. These findings argue that tacrine at concentrations higher
      than 2 x 10(-5) mol/L has a desensitizing effect on the contractile apparatus of
      gastric corpus smooth muscle preparations towards Ca2+.

PMID- 17218978
TI  - Chronic estrogen treatment reduces vaso-constrictor responses in insulin
      resistant rats.
AB  - Previous experiments have shown that chronic estrogen treatment via subcutaneous
      implants prevented insulin-induced blood pressure elevation and increased insulin
      sensitivity in ovariectomized female rats. In vitro vascular studies were
      performed using isolated mesenteric arteries to determine the effect of chronic
      estrogen and insulin treatments on vascular responses to vasoconstrictor agents.
      Female Wistar rats were assigned to the following groups: sham-operated, sham
      operated plus insulin, sham-operated plus insulin plus estrogen, ovariectomized,
      ovariectomized plus insulin, and ovariectomized plus insulin plus estrogen.
      Chronic insulin and estrogen treatments were initiated with subcutaneous
      placement of insulin implants (2 U/d) and 17beta-estradiol implants (0.5
      mg/pellet, 60 day release) at the back of the neck. After 8 weeks of treatment,
      mesenteric arteries were isolated for assessment of constrictor responses to
      norepinephrine and the thromboxane A2 analogue U46619 in the presence or absence
      of the endothelium. The results show that chronic estrogen treatment attenuated
      the vascular constrictor responses to norepinephrine and U46619 only in
      endothelium intact vessels. Incubation with insulin did not significantly affect
      norepinephrine-induced vascular smooth muscle contraction. The study provides
      evidence that the mechanism by which estrogen prevents insulin-induced blood
      pressure elevation in insulin-treated ovariectomized rats is by influencing
      endothelium-derived vasoactive factors such as thromboxane A2.

PMID- 17218979
TI  - Acute hemorrhage causes hepatic insulin sensitizing substance (HISS)-dependent
      insulin resistance.
AB  - Hepatic insulin sensitizing substance (HISS) has been shown to account for 55% of
      the action of insulin in the fed state. HISS blockade leads to HISS-dependent
      insulin resistance (HDIR). The objective of this study was to test the hypothesis
      that insulin resistance produced by hemorrhage was HDIR. Insulin sensitivity was
      measured using the rapid insulin sensitivity test (RIST), which can identify HISS
      dependent and independent components. Hemorrhage was performed in anesthetized
      rats by removing blood to reduce mean arterial pressure to 50 mmHg. Subsequent to
      blood removal, a RIST was performed. The results show that hemorrhage caused
      complete HDIR as subsequent administration of atropine failed to further reduce
      insulin sensitivity. However, the post-hemorrhage RIST was reduced by 34% and not
      the anticipated 55%. The lesser reduction of the RIST index by hemorrhage was
      related to reduced apparent volume of distribution and clearance of insulin,
      since occlusion of the superior mesenteric artery, which caused a similar
      decrease in portal venous flow as did hemorrhage, resulted in a similar degree of
      reduction of insulin clearance. The response to administered insulin was
      confounded by the impact of reduced hepatic blood flow on insulin metabolism that
      resulted in an increase in the HISS independent (direct) action of injected
      insulin against a background of complete HDIR. HDIR represents a useful hormonal
      response to assure a hyperglycemic response to hemorrhage.

PMID- 17218980
TI  - M3 muscarinic receptor-deficient mice retain bethanechol-mediated intestinal ion
      transport and are more sensitive to colitis.
AB  - Acetylcholine (ACh) is an important regulator of intestinal epithelial ion
      transport via muscarinic or nicotinic ACh receptors. Previous studies emphasize
      the role of the M3 muscarinic receptor subtype in mediating the effects of
      cholinergic agonists on intestinal ion transport. With the prevalence of mouse
      models to study intestinal (patho)physiology, it is crucial that ion transport be
      understood in this species. Using M3 receptor-deficient (KO) mice and wild-type
      (WT) mice, we examined M3 receptor contributions to ion transport as well as its
      role in colitis induced by dextran sodium sulphate (DSS). In the Ussing chambers,
      ileal and colonic tissue from M3 KO and WT mice displayed similar baseline ion
      transport properties. Short-circuit current (ISC) responses to the muscarinic
      receptor agonist bethanechol were slightly decreased in ileal tissue from M3 KO
      mice compared with tissue from WT mice, whereas responses were not significantly
      different in colonic tissue. ISC responses to bethanechol were partially
      inhibited by pirenzepine in WT ileum, but not tetrodotoxin, suggesting
      involvement of a non-neuronal M1 muscarinic receptor. In the ileum, the M3
      receptor may inhibit neuronally evoked ion transport, as indicated by the
      increased ISC responses to electrical stimulation in tissue from M3 KO mice.
      Furthermore, whereas all DSS-treated mice developed colitis, M3 KO mice displayed
      more rapid mass loss and more severe disease than DSS-treated WT mice, even
      following a reduction in the amount and time of DSS treatment. Thus, M3 receptor
      KO mice are compensated in their ability to evoke muscarinic receptor-driven ion
      transport responses, but are more sensitive to DSS. This work highlights the need
      to dissect muscarinic receptor-mediated events in the mouse, as mice become
      increasingly valuable in enteric disease models.

PMID- 17218981
TI  - Angiotensin-(1-7) potentiates responses to bradykinin but does not change
      responses to angiotensin I.
AB  - Angiotensin-(1-7) (Ang-(1-7)), a bioactive peptide in the renin-angiotensin
      system, has counterregulatory actions to angiotensin II (Ang II). However, the
      mechanism by which Ang-(1-7) enhances vasodepressor responses to bradykinin (BK)
      is not well understood. In the present study, the effects of Ang-(1-7) on
      responses to BK, BK analogs, angiotensin I (Ang I), and Ang II were investigated
      in the anesthetized rat. The infusion of Ang-(1-7) (55 pmol/min i.v.) enhanced
      decreases in systemic arterial pressure in response to i.v. injections of BK and
      the BK analogs [Hyp3, Tyr(Me)8]-bradykinin (HT-BK) and [Phe8psi (CH2-NH) Arg9]
      bradykinin (PA-BK) without altering pressor responses to Ang I or II, or
      depressor responses to acetylcholine and sodium nitroprusside. The angiotensin
      converting enzyme (ACE) inhibitor enalaprilat enhanced responses to BK and the BK
      analog HT-BK without altering responses to PA-BK and inhibited responses to Ang
      I. The potentiating effects of Ang-(1-7) and enalaprilat on responses to BK were
      not attenuated by the Ang-(1-7) receptor antagonist A-779. Ang-(1-7)- and ACE
      inhibitor-potentiated responses to BK were attenuated by the BK B2 receptor
      antagonist Hoe 140. The cyclooxygenase inhibitor sodium meclofenamate had no
      significant effect on responses to BK or Ang-(1-7)-potentiated BK responses.
      These results suggest that Ang-(1-7) potentiates responses to BK by a selective
      B2 receptor mechanism that is independent of an effect on Ang-(1-7) receptors,
      ACE, or cyclooxygenase product formation. These data suggest that ACE inhibitor
      potentiated responses to BK are not mediated by an A-779-sensitive mechanism and
      are consistent with the hypothesis that enalaprilat-induced BK potentiation is
      due to decreased BK inactivation.

PMID- 17218982
TI  - Intrahepatic adenosine-mediated activation of hepatorenal reflex is via A1
      receptors in rats.
AB  - Previous studies have shown that intrahepatic adenosine is involved in activation
      of the hepatorenal reflex that regulates renal sodium and water excretion. The
      present study aims to determine which subtype of adenosine receptors is
      implicated in the process. Mean arterial pressure, portal venous pressure and
      flow, and renal arterial flow were monitored in pentobarbital anesthetized rats.
      Urine was collected from the bladder. Intraportal administration of 8-cyclopentyl
      1,3-dipropylxanthine (DPCPX), a selective adenosine A1 receptor antagonist,
      increased urine flow by 24%, 89%, and 143% at the dose of 0.01, 0.03, and 0.1 mg
      x kg(-1), respectively; in contrast, DPCPX, when administered intravenously at
      the same doses, only increased urine flow by 0%, 18%, and 36%. The increases in
      urine flow induced by intraportal administration of DPCPX were abolished in rats
      with liver denervation. Intrahepatic infusion of adenosine significantly
      decreased urine flow and this response was abolished by intraportal
      administration of DPCPX. Neither intraportal nor intravenous administration of
      3,7-dimethyl-1-propargylxanthine, a selective adenosine A2 receptor antagonist,
      showed significant influence on urine flow. Systemic arterial pressure, renal
      blood flow and glomerular filtration rate were unaltered by the administration of
      any of the drugs. In conclusion, intrahepatic adenosine A1 receptors are
      responsible for the adenosine-mediated hepatorenal reflex that regulates renal
      water and sodium excretion.

PMID- 17218983
TI  - Inhibition of nonexocytotic norepinephrine release by desipramine reduces
      myocardial infarction size.
AB  - During myocardial ischemia, a substantial accumulation of norepinephrine occurs
      in the ischemic zone due to a local nonexocytotic release of norepinephrine.
      Norepinephrine release is driven by the neuronal monoamine transporter (NET),
      which reverses its usual transmembrane transport direction. We investigated
      whether this local accumulation of norepinephrine contributes to irreversible
      myocardial injury in an in vivo model of myocardial infarction. Male,
      anaesthetized Wistar rats were subjected to 30 min coronary occlusion and
      subsequent 120 min reperfusion. Five minutes prior to coronary occlusion, the NET
      inhibitor desipramine was administered intravenously. Infarct size (IS) was
      determined by TTC-staining and was related to the area at risk (AAR). The
      influence of desipramine on cardiac norepinephrine release was investigated in
      isolated perfused hearts with 30 min of regional ischemia. Norepinephrine was
      measured in the effluent from the hearts by HPLC and electrochemical detection.
      Desipramine (0.1-0.8 mg/kg) dose-dependently reduced infarct size (IS/AAR) from
      0.54 to 0.21 and suppressed postischemic norepinephrine release from 245 to 108
      pg/mL. In summary, the data indicate that nonexocytotic release of norepinephrine
      in myocardial ischemia exaggerates acute ischemic damage, because suppression of
      ischemia-induced release of norepinephrine by the tricyclic antidepressant
      desipramine effectively reduces infarct size in an in vivo model of myocardial
      ischemia.

PMID- 17218984
TI  - Morphological and biochemical alterations in the jejunum following iodoacetamide
      induced colitis in rats.
AB  - This study aims to describe the morphological alterations in the small and large
      intestines as well as the expression of some enterocyte enzymes and carriers in a
      rat model of iodoacetamide-induced colitis. Biopsies from the large and small
      intestines were taken at 1, 2, 4, 8, and 16 days postinduction and studied by
      light microscopy. The expressions of lactase, sucrase, aminopeptidase, and Glut-5
      in the jejunum were studied by immunohistochemistry. Gene expressions of
      enterocyte lactase and sucrase were determined by RT-PCR using specific
      oligonucleotides. Microscopic examination of the large intestines revealed
      manifestations concordant with inflammation. Such alterations peaked at 2 days,
      were maintained to a lesser extent for 4 days, regressed by 8 days, and healed by
      16 days. In the jejunum, the expression of lactase, sucrase, and aminopeptidase
      decreased 2 days after colitis induction, and recovered 2 days later. Similarly,
      Glut-5 expression decreased transiently with partial recovery by day 8. Compared
      with sham, gene expression of jejunal brush border enzymes sucrase and lactase
      showed a 4-fold increase in lactase and a 9-fold increase in sucrase after 4
      days. We conclude that colitis can induce significant functional abnormalities in
      distant noninflamed small bowel regions.

PMID- 17218985
TI  - The rapid onset of hyperglycaemia in ZDF rats was associated with a widespread
      alteration of metabolic proteins implicated in glucose metabolism in the heart.
AB  - The present study tested the hypothesis that the phosphorylation and regulation
      of metabolic proteins implicated in glucose homeostasis were impaired in the
      heart of the type 2 diabetic Zucker-diabetic-fatty (ZDF) rat model. The onset of
      hyperglycaemia in ZDF rats was not uniform, instead it either progressed rapidly
      (3-4 weeks) or was delayed (6-8 weeks). In both the early and late onset
      hyperglycaemic ZDF rats, AMPKalpha Thr172 phosphorylation in the heart was
      significantly decreased. In the early onset hyperglycaemic ZDF rats, PKB Ser473
      phosphorylation was reduced, whereas Thr308 phosphorylation was significantly
      increased. In the late onset hyperglycaemic ZDF rats, PKB Ser473 phosphorylation
      was unchanged, but Thr308 phosphorylation remained elevated. Cardiac GLUT4
      protein and mRNA expression were significantly reduced in the early onset
      hyperglycaemic ZDF rats, whereas increased protein expression was observed in the
      late onset hyperglycaemic ZDF rats. In conclusion, the present study has
      demonstrated that following a more rapid onset of hyperglycaemia, the type 2
      diabetic heart is more prone to alterations in the signaling proteins implicated
      in glucose metabolism.

PMID- 17218986
TI  - Malonyl CoA control of fatty acid oxidation in the newborn heart in response to
      increased fatty acid supply.
AB  - The concentration of fatty acids in the blood or perfusate is a major determinant
      of the extent of myocardial fatty acid oxidation. Increasing fatty acid supply in
      adult rat increases myocardial fatty acid oxidation. Plasma levels of fatty acids
      increase post-surgery in infants undergoing cardiac bypass operation to correct
      congenital heart defects. How a newborn heart responds to increased fatty acid
      supply remains to be determined. In this study, we examined whether the tissue
      levels of malonyl CoA decrease to relieve the inhibition on carnitine
      palmitoyltransferase (CPT) I when the myocardium is exposed to higher
      concentrations of long-chain fatty acids in newborn rabbit heart. We then tested
      the contribution of the enzymes that regulate tissue levels of malonyl CoA,
      acetyl CoA carboxylase (ACC), and malonyl CoA decarboxylase (MCD). Our results
      showed that increasing fatty acid supply from 0.4 mmol/L (physiological) to 1.2
      mmol/L (pathological) resulted in an increase in cardiac fatty acid oxidation
      rates and this was accompanied by a decrease in tissue malonyl CoA levels. The
      decrease in malonyl CoA was not related to any alterations in total and
      phosphorylated acetyl CoA carboxylase protein or the activities of acetyl CoA
      carboxylase and malonyl CoA decarboxylase. Our results suggest that the
      regulatory role of malonyl CoA remained when the hearts were exposed to high
      levels of fatty acids.

PMID- 17218987
TI  - Thermodynamic stoichiometry of Na+-coupled glutathione transport.
AB  - Ambiguity exists with respect to mechanisms of glutathione (GSH) transport and
      the molecular identity of GSH transporters. Empirical and theoretical limitations
      have hindered functional and molecular characterizations. Published literature
      referring to the isolation and molecular identification of Na+-coupled GSH
      transporters that mediate the cellular uptake of GSH is highly debated. Whereas a
      number of functional and kinetic reports of this putative symport mechanism
      exist, the hypothetical transmembrane Na+-coupled GSH transporter protein or the
      genetic message encoding it has not been isolated. Theoretical thermodynamic
      calculations to support the concept of secondary active GSH transport and to
      rationalize accounts of physical-kinetic measurements describing Na+-coupled
      cellular GSH uptake were performed. The adequacy of requisite energy and
      stoichiometric conservation of the separate electrical and chemical components of
      a Na+ gradient in maintaining a high cellular accumulation gradient for GSH was
      examined through a purely phenomenological perspective. Dependent on the
      biological context, the energetic coupling between Na+ and GSH cotransport may
      occur at ratios from 1:1 to 3:1. Molecular identification of specific
      transporters responsible for cellular Na+-coupled GSH uptake will facilitate
      determination of their relative contribution to the overall plasma membrane
      resting potential. In tissues with a high GSH concentration relative to their
      extracellular milieu, particularly in pathologies of cystic fibrosis and dry eye
      syndromes, large energy coupling ratios in cotransport of Na+ and GSH may be
      expected. Na+-coupled GSH transport may play an important role in disease onset
      and (or) progression, or treatment modalities thereof.

PMID- 17218988
TI  - Targeting TACE-dependent EGFR ligand shedding in breast cancer.
AB  - The ability to proliferate independently of signals from other cell types is a
      fundamental characteristic of tumor cells. Using a 3D culture model of human
      breast cancer progression, we have delineated a protease-dependent autocrine loop
      that provides an oncogenic stimulus in the absence of proto-oncogene mutation.
      Targeting this protease, TNF-alpha-converting enzyme (TACE; also referred to as a
      disintegrin and metalloproteinase 17 [ADAM17]), with small molecular inhibitors
      or siRNAs reverted the malignant phenotype in a breast cancer cell line by
      preventing mobilization of 2 crucial growth factors, TGF-alpha and amphiregulin.
      We show that TACE-dependent ligand shedding was prevalent in a series of
      additional breast cancer cell lines and, in all cases examined, was amenable to
      inhibition. Using existing patient outcome data, we demonstrated a strong
      correlation between TACE and TGFA expression in human breast cancers that was
      predictive of poor prognosis. Tumors resulting from inappropriate activation of
      the EGFR were common in multiple tissues and were, for the most part, refractory
      to current targeted therapies. The data presented here delineate the molecular
      mechanism by which constitutive EGFR activity may be achieved in tumor
      progression without mutation of the EGFR itself or downstream pathway components
      and suggest that this important oncogenic pathway might usefully be targeted
      upstream of the receptor.

PMID- 17218989
TI  - Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis.
AB  - Wiskott-Aldrich syndrome protein (WASp) is essential for optimal T cell
      activation. Patients with WAS exhibit both immunodeficiency and a marked
      susceptibility to systemic autoimmunity. We investigated whether alterations in
      Treg function might explain these paradoxical observations. While WASp-deficient
      (WASp(-/-)) mice exhibited normal thymic Treg generation, the competitive fitness
      of peripheral Tregs was severely compromised. The total percentage of forkhead
      box P3-positive (Foxp3(+)) Tregs among CD4(+) T cells was reduced, and WASp(-/-)
      Tregs were rapidly outcompeted by WASp(+) Tregs in vivo. These findings
      correlated with reduced expression of markers associated with self-antigen-driven
      peripheral Treg activation and homing to inflamed tissue. Consistent with these
      findings, WASp(-/-) Tregs showed a reduced ability to control aberrant T cell
      activation and autoimmune pathology in Foxp3(-/-)Scurfy (sf) mice. Finally,
      WASp(+) Tregs exhibited a marked selective advantage in vivo in a WAS patient
      with a spontaneous revertant mutation, indicating that altered Treg fitness
      likely explains the autoimmune features in human WAS.

PMID- 17218990
TI  - Genome-wide reverse genetics framework to identify novel functions of the
      vertebrate secretome.
AB  - BACKGROUND: Understanding the functional role(s) of the more than 20,000 proteins
      of the vertebrate genome is a major next step in the post-genome era. The
      approximately 4,000 co-translationally translocated (CTT) proteins - representing
      the vertebrate secretome - are important for such vertebrate-critical processes
      as organogenesis. However, the role(s) for most of these genes is currently
      unknown. RESULTS: We identified 585 putative full-length zebrafish CTT proteins
      using cross-species genomic and EST-based comparative sequence analyses. We
      further investigated 150 of these genes (Figure 1) for unique function using
      morpholino-based analysis in zebrafish embryos. 12% of the CTT protein-deficient
      embryos resulted in specific developmental defects, a notably higher rate of gene
      function annotation than the 2%-3% estimate from random gene mutagenesis studies.
      CONCLUSION: This initial collection includes novel genes required for the
      development of vascular, hematopoietic, pigmentation, and craniofacial tissues,
      as well as lipid metabolism, and organogenesis. This study provides a framework
      utilizing zebrafish for the systematic assignment of biological function in a
      vertebrate genome.

PMID- 17218991
TI  - Multiplexed SNP typing of ancient DNA clarifies the origin of Andaman mtDNA
      haplogroups amongst South Asian tribal populations.
AB  - The issue of errors in genetic data sets is of growing concern, particularly in
      population genetics where whole genome mtDNA sequence data is coming under
      increased scrutiny. Multiplexed PCR reactions, combined with SNP typing, are
      currently under-exploited in this context, but have the potential to genotype
      whole populations rapidly and accurately, significantly reducing the amount of
      errors appearing in published data sets. To show the sensitivity of this
      technique for screening mtDNA genomic sequence data, 20 historic samples of the
      enigmatic Andaman Islanders and 12 modern samples from three Indian tribal
      populations (Chenchu, Lambadi and Lodha) were genotyped for 20 coding region
      sites after provisional haplogroup assignment with control region sequences. The
      genotype data from the historic samples significantly revise the topologies for
      the Andaman M31 and M32 mtDNA lineages by rectifying conflicts in published data
      sets. The new Indian data extend the distribution of the M31a lineage to South
      Asia, challenging previous interpretations of mtDNA phylogeography. This genetic
      connection between the ancestors of the Andamanese and South Asian tribal groups
      approximately 30 kya has important implications for the debate concerning
      migration routes and settlement patterns of humans leaving Africa during the late
      Pleistocene, and indicates the need for more detailed genotyping strategies. The
      methodology serves as a low-cost, high-throughput model for the production and
      authentication of data from modern or ancient DNA, and demonstrates the value of
      museum collections as important records of human genetic diversity.

PMID- 17218994
TI  - Professionalism: looking for your blind spots.

PMID- 17218993
TI  - The journal numbers game.

PMID- 17218992
TI  - The interplay of discourse congruence and lexical association during sentence
      processing: Evidence from ERPs and eye tracking.
AB  - Five experiments used ERPs and eye tracking to determine the interplay of word
      level and discourse-level information during sentence processing. Subjects read
      sentences that were locally congruent but whose congruence with discourse context
      was manipulated. Furthermore, critical words in the local sentence were preceded
      by a prime word that was associated or not. Violations of discourse congruence
      had early and lingering effects on ERP and eye-tracking measures. This indicates
      that discourse representations have a rapid effect on lexical semantic processing
      even in locally congruous texts. In contrast, effects of association were more
      malleable: Very early effects of associative priming were only robust when the
      discourse context was absent or not cohesive. Together these results suggest that
      the global discourse model quickly influences lexical processing in sentences,
      and that spreading activation from associative priming does not contribute to
      natural reading in discourse contexts.

PMID- 17218995
TI  - Image-guided radiofrequency ablation of liver malignancies: experience at
      Singapore General Hospital.
AB  - The aim of this paper was to study the efficacy, side effects and complications
      of radiofrequency (RF) ablation of primary and metastatic liver malignancies.
      MATERIALS AND METHODS: We retrospectively reviewed 57 patients (39 men, 18 women;
      mean age, 63 years; age range, 44 to 83 years) who underwent RF ablation for
      liver malignancies from January 2002 to December 2004. A total of 87 tumours were
      ablated - 71 (81.6%) hepatocellular carcinomas and 16 (18.4%) metastases (from
      primaries in the colon, stomach and pancreas). RF ablation was performed either
      percutaneously (n = 71) under conscious sedation or intraoperatively (n = 16)
      under general anaesthesia. Follow-up ranged from 1 month to 41 months (mean,
      15.2) and included computed tomography (CT) 1 day, 1 month and 3 months after
      ablation, and half-yearly thereafter. Patients were observed for local tumour
      progression and for the emergence of new tumours. RESULTS: Four patients with a
      total of 5 tumours were lost to follow-up. Of the remaining 82 tumours treated,
      complete ablation was attained in 66 tumours after a single procedure, giving a
      primary effectiveness rate of 80.5%. Seven (8.5%) required 2 procedures to
      achieve complete ablation, giving a secondary effectiveness rate of 89% after 2
      ablations. One tumour (1.2%) required 3 procedures to achieve complete ablation.
      One tumour required 4 procedures to date, with the latest follow-up CT still
      demonstrating incomplete ablation. Two tumours (2.4%) had an initial RF ablation
      and subsequent transarterial chemoembolisation (TACE). One tumour had an initial
      RF ablation followed by 32Phosphorus-biosilicon (BrachySil) injection, the latter
      as part of a Phase IIA trial. One tumour required 2 RF ablations and a subsequent
      TACE. Lastly, 3 tumours received initial RF ablation but subsequent local tumour
      progression was not treated as the patients were deemed unfit for repeat
      ablation. No procedure-related deaths or major complications were encountered.
      Minor complications were reported in 2 patients (3.8%) - subcapsular haematoma
      and thermal injury to the adjacent gastric antrum, both not necessitating
      surgical intervention. CONCLUSIONS: RF ablation is an effective, safe and
      relatively simple procedure for the treatment of unresectable liver malignancies.

PMID- 17218996
TI  - Use of D-dimer and lower extremity Doppler ultrasound results to obviate the need
      for computerised tomographic pulmonary angiography.
AB  - We hypothesise that correct interpretation of other diagnostic tests could reduce
      the use of computerised tomographic pulmonary angiogram (CTPA) examinations in
      patients with suspected pulmonary embolism (PE). MATERIALS AND METHODS: We
      carried out a retrospective analysis of 158 patients in a 928-bed university
      hospital. These consecutive patients were investigated for suspected PE from May
      2001 to February 2002 using CTPA. RESULTS: There were 74 men and 84 women with a
      mean (+/-SD) age of 57 (+/-19) years. Overall, 56% of patients (89/158) showed
      clinically significant abnormalities on the CTPA examination. The overall
      prevalence of PE was 15% (24/158). The D-dimers were assayed in 40% (63/158) and
      lower limbs were scanned with Doppler ultrasound (US) in 22% (35/158) of
      patients. None of the 19 patients with negative D-dimer assays had PE. Of the
      patients who were positively tested on Doppler US, 4 were positive and 1 was
      negative for PE on the CTPA. None of the patients with positive Doppler US had
      negative D-dimer test. In retrospect, patient management based on negative D
      dimer assays and positive lower extremity Doppler US studies could have reduced
      the need for further investigation with CTPA by 15% (24/158). CONCLUSION: In
      patients with suspected PE, correct interpretation of D-dimer and leg Doppler US
      tests may reduce the demand for CTPAs.

PMID- 17218997
TI  - Electrophysiological findings in persons with nyctalopia.
AB  - INTRODUCTION: Ophthalmologists are occasionally confronted with an individual
      presenting with nyctalopia (i.e., a relatively greater difficulty seeing at
      night). When there is no accompanying abnormality seen in the fundus, visual
      electrophysiology becomes useful as an objective means of assessing rod
      (scotopic) photoreceptor function or pathway defects. MATERIALS AND METHODS: A
      retrospective study was performed on 50 consecutive patients, aged less than 40
      years, with seemingly normal fundi and good vision [visual acuity (VA) >6/12]
      presenting to the Visual Electrodiagnostic Unit, Singapore National Eye Centre,
      for the investigation of nyctalopia over a 2-year period. Subjective scotopic
      threshold sensitivity (STS) and objective full-field electroretinogram (ERG) were
      performed. Persons with abnormal test results were identified. RESULTS: Normal
      ERG scotopic responses were obtained in 74% of subjects. There was no significant
      difference in age, refraction and STS levels between subjects with abnormal and
      normal ERG. In the group with abnormal scotopic ERG responses, 9 were identified
      to have nonspecific rod dysfunction, 2 had rod-cone dystrophies and 2 had ERG
      changes suggestive of congenital stationary night blindness (CSNB). CONCLUSION: A
      large number of subjects presenting with nyctalopia had normal ERG findings. We
      can only assume that in these patients, no significant rod pathway dysfunction
      exists and that optical (e.g., night or instrument myopia) and psychological
      aetiologies should be considered. The fact that an abnormal result occurs in 26%,
      however, suggests that ncytalopia should be evaluated with electrophysiolgoical
      testing even when the fundi appear normal.

PMID- 17218998
TI  - Accommodative stimulus response curve of emmetropes and myopes.
AB  - INTRODUCTION: Myopes are suspected to be poorer at responding to accommodative
      stimuli than emmetropes, and this may worsen the degree of their myopia. The
      study aims to compare the abilities of young adult emmetropes and myopes in
      responding to accommodative stimuli, as indicated by their Accommodation Stimulus
      Response Curves (ASRCs) in a predominantly Chinese population. MATERIALS AND
      METHODS: Seventeen emmetropes and 33 myopes aged between 16 and 23 years (mean,
      18.6 +/- 1.2) were recruited, of whom 11 were progressing and 22 were non
      progressing myopes. The ASRC gradients of subjects were measured using the
      methods of decreasing distance series (DDS), positive (PLS) and negative lens
      series (NLS). RESULTS: The ASRC is method dependent. The gradients of the curves
      are significantly different among 3 methods of measurement using single-factor
      ANOVA (F3.057 = 44.815, P <0.01). The slopes of the accommodative errors of all
      subjects were steeper using the NLS method, and the lags of accommodation
      increased with elevated demands. No significant differences in ASRC gradients
      were found between emmetropes, non-progressing myopes and progressing myopes for
      the range of accommodative demands for each method. Progressing myopes showed the
      highest error towards the higher demand compared with the emmetropes and non
      progressing myopes. CONCLUSION: Accommodative responses of myopes were more
      sluggish though there were no statistical differences in ASRC gradients between
      emmetropes and myopes. It is not certain if the poorer accommodative responses
      were a cause, or a consequence, of myopia.

PMID- 17218999
TI  - The effectiveness of transvaginal anterior colporrhaphy reinforced with
      polypropylene mesh in the treatment of severe cystoceles.
AB  - INTRODUCTION: Grade 4 cystoceles are among the most challenging to achieve a
      successful repair for gynaecologists. The high rate of recurrence of severe
      prolapse encouraged surgeons to use meshes. Only recently have meshes been used
      transvaginally for pelvic organ prolapse. The aim of our pilot study was
      therefore to determine the effectiveness of transvaginal anterior colporrhaphy
      reinforced with prolene mesh in the treatment of severe or recurrent cystoceles
      by looking at their primary surgical outcomes as well as their complications.
      MATERIALS AND METHODS: This was a retrospective study conducted by the
      urogynaecology unit at KK Women's and Children's Hospital (KKWCH) in Singapore
      based on operations performed from April 2002 to December 2003. The inclusion
      criterion was that women had to have at least a grade 4 or recurrent grade 3
      cystocele and had undergone a vaginal anterior colporrhaphy reinforced with
      prolene mesh. The women were further subdivided into 3 groups depending on
      whether vaginal hysterectomies were performed or not as well as the absence or
      presence of the uterus. RESULTS: Thirty-seven patients with severe cystoceles
      underwent this procedure. The 3 mean follow-up times for the 3 groups ranged from
      14.4 to 19.2 months (range, 2 to 32). Overall for the 3 groups, 75.7% were cured
      with no or grade 1 cystocele, 18.9% had asymptomatic grade 2 cystocele while 5.4%
      developed grade 3 or 4 cystocele. There were no mesh erosions. CONCLUSION:
      Transvaginal anterior colporrhaphy reinforced with a tension-free prolene mesh in
      the treatment of severe or recurrent cystoceles is simple, safe, easily performed
      and is associated with a low failure rate and morbidity.

PMID- 17219000
TI  - Gender disparity in paediatric hospital admissions.
AB  - INTRODUCTION: To determine the magnitude of gender difference in paediatric
      hospital admissions. MATERIALS AND METHODS: We reviewed discharge data of general
      medical paediatric admissions to a university teaching hospital in Hong Kong from
      1984 to 2000. Based on ICD-9 codes, 9 broad categories of disease with related
      sub-categories were used, namely respiratory, gastrointestinal, neurological,
      renal, cardiac, haematological/oncological, neonatal, miscellaneous and social.
      Data on patients admitted to the haematological, oncological and neonatal wards
      were excluded from this analysis. RESULTS: There were 92,332 patients admitted to
      the general paediatric wards. The 7 leading causes for admission accounted for
      62% of all admissions: gastroenteritis (14%), upper respiratory tract infections
      (12%), asthma/wheezy bronchitis (10%), pneumonia (10%), bronchiolitis (6%),
      febrile convulsions (7%) and other convulsions (4%). Across almost all
      categories, there was a consistent excess of males (59.1% of all admissions). The
      male excess was even more pronounced for urinary tract infections (72%) and
      nephrotic syndrome (80%). The main sub-categories without this male predominance
      were accidents, accidental ingestion and social admissions (50% males), failure
      to thrive (49% males), acyanotic congenital heart disease (48%), endocrine (42%),
      auto-immune conditions (30%) and attempted suicide (19%). CONCLUSIONS: Although
      male vulnerability to illness has long been recognised, the consistency and
      magnitude of these gender differentials in admissions was impressive. More
      vigorous exploration of the underlying mechanisms responsible for this phenomenon
      is warranted.

PMID- 17219001
TI  - Benign parotid lesions: is near total parotidectomy justified?
AB  - INTRODUCTION: Benign tumours of the parotid gland constitute about 80% of parotid
      tumours. The most common benign tumour of the parotid gland is pleomorphic
      adenoma. Other conditions, like Kimura's disease, may mimic a tumour when they
      present as a parotid mass. Various modes of treatment have been advocated for the
      treatment of benign parotid lesions, ranging from enucleation to near-total
      parotidectomy. MATERIAL AND METHODS: This is an audit of an 18-year period where
      173 lesions of the parotid gland (34 malignant and 139 benign lesions) were
      treated by the author. RESULTS: There were 139 benign lesions, of which 123 were
      benign tumours and 16 non-tumour conditions. Fourteen cases of recurrent
      pleomorphic adenoma of parotid that had been treated elsewhere were also operated
      on. Near-total parotidectomy was performed on all these cases with benign
      lesions. CONCLUSIONS: There has been no recurrence in all the patients who was
      treated this way. Near-total parotidectomy should be considered when there is a
      need to treat benign parotid swellings.

PMID- 17219002
TI  - Unravelling the mystery in a case of persistent ACTH-independent Cushing's
      syndrome.
AB  - INTRODUCTION: We present a rare variety of adrenocorticotrophic hormone (ACTH)
      independent Cushing's syndrome known as primary pigmented nodular adrenocortical
      disease (PPNAD). CLINICAL PICTURE: The patient initially underwent unilateral
      adrenalectomy for what was thought to be a left adrenal adenoma. OUTCOME: Partial
      resolution of symptoms and demonstrable persistent hypercortisolism after surgery
      prompted further evaluation with findings leading to the diagnosis of Carney
      complex. A review of the adrenal histology was consistent with PPNAD. CONCLUSION:
      This entity of PPNAD, which has rarely been reported in Asians, forms part of the
      Carney complex. The diagnosis may not be simple and straightforward, as
      illustrated in this patient.

PMID- 17219003
TI  - Skin manifestation of Stenotrophomonas maltophilia infection--a case report and
      review article.
AB  - INTRODUCTION: Stenotrophomonas maltophilia is an aerobic gram-negative bacillus
      that is a frequent coloniser of fluids used in the hospital setting. It causes
      infection in immunosuppressed hosts, especially those who are neutropaenic, on
      chemotherapy and broad spectrum antibiotics. Skin and soft tissue manifestations
      of Stenotrophomonas maltophilia infection are becoming an increasingly recognised
      entity; the clinical spectrum ranges from mucocutaneous, skin to soft tissue
      infections. MATERIALS AND METHODS: We present a case of an 8-year-old girl with
      acute myeloid leukaemia who developed metastatic skin lesions secondary to
      Stenotrophomonas maltophilia bacteraemia. The authors reviewed a total of 24
      reported cases of mucocutaneous, skin and soft tissue infections by
      Stenotrophomonas maltophilia. The presentations include metastatic cellulitis,
      primary cellulitis and infected mucocutaneous ulcers. RESULTS: This is the first
      locally reported case of metastatic nodular skin lesions caused by
      Stenotrophomonas maltophilia bacteraemia. This is also the first reported
      paediatric case of embolic skin lesions caused by Stenotrophomonas maltophilia.
      Of the 6 cases of Stenotrophomonas maltophilia bacteraemia seen in the paediatric
      oncology patients from year 2000 to 2004 at our hospital, only 1 case developed
      metastatic skin lesions. CONCLUSION: Stenotrophomonas maltophilia skin infection
      should be included into the list of differential diagnoses for metastatic skin
      lesions in neutropaenic patients, especially with an underlying haematologic
      malignancy who has received recent chemotherapy and broad spectrum antibiotics.
      Haematologic malignancy, transplantation, neutropaenic, immunosuppressive therapy
      and a high severity of illness score were important prognostic factors.

PMID- 17219004
TI  - Clinical report: a case of Williams Syndrome and Klinefelter Syndrome.
AB  - INTRODUCTION: Williams syndrome (WS) is a rare but well recognised
      neurodevelopmental disease affecting the connective tissue and the central
      nervous system. Many patients are identified through the presence of dysmorphic
      features and associated cardiac abnormalities. Klinefelter syndrome (KS) is
      associated with gynaecomastia, small testes, azoospermia and elevated
      gonadotropin levels. They are recognised in the second decade of life by their
      tall stature and delay in pubertal development. A combination of constitutive WS
      and KS has yet to be described. CLINICAL PICTURE: We report a child with these
      genetic aberrations, highlighting the clinical characteristics of such an
      individual. CONCLUSION: The manifestations and interactions of both conditions
      are also discussed.

PMID- 17219005
TI  - Bile duct perforation in children: is it truly spontaneous?
AB  - INTRODUCTION: Bile duct perforation (BDP) with resultant biliary ascites in
      children is a rare clinical condition. The aetiopathogenesis is still an enigma,
      with increasing evidence suggesting anomalous union of pancreaticobiliary ductal
      (AUPBD) system as the prime causative factor. CLINICAL PICTURE: We report 2 cases
      of spontaneous perforation of the bile duct confirmed on histopathological
      examination as choledochal cyst, in a 6-month-old female child and a 4-year-old
      boy who presented with subtle clinical symptoms. TREATMENT AND OUTCOME: Both
      patients were successfully managed by excision of the gall bladder and common
      bile duct and Roux-en- Y hepaticojejunostomy. This procedure was performed
      following initial cholecystostomy drainage in the second case. CONCLUSIONS: From
      the available literature and experience with our patients, BDP is not merely
      spontaneous but may be related to AUPBD and choledochal cyst.

PMID- 17219006
TI  - The haze and health: a blog about the fog.

PMID- 17219007
TI  - The journal impact factor: too much of an impact?
AB  - INTRODUCTION: The journal impact factor is often used to judge the scientific
      quality of individual research articles and individual journals. Despite numerous
      reviews in the literature criticising such use, in some countries the impact
      factor has become an outcome measure for grant applications, job applications,
      promotions and bonuses. The aim of this review is to highlight the major issues
      involved with using the journal impact factor as a measure of research quality.
      METHODS: A literature review of articles on journal impact factors, science
      citation index, and bibliometric methods was undertaken to identify relevant
      articles. RESULTS: The journal impact factor is a quantitative measure based on
      the ratio between yearly citations in a particular journal to total citations in
      that journal in the previous 2 years. Its use as a criterion for measuring the
      quality of research is biased. The major sources of bias include database
      problems from the Institute for Scientific Information and research field
      effects. The journal impact factor, originally designed for purposes other than
      the individual evaluation of research quality, is a useful tool provided its
      interpretation is not extrapolated beyond its limits of validity. CONCLUSION:
      Research quality cannot be measured solely using the journal impact factor. The
      journal impact factor should be used with caution, and should not be the dominant
      or only factor determining research quality.

PMID- 17219009
TI  - Three novel mutations in the activin receptor-like kinase 1 (ALK-1) gene in
      hereditary hemorrhagic telangiectasia type 2 in Brazilian patients.
AB  - Hereditary hemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber disease is a
      systemic fibrovascular dysplasia with an autosomal dominant inheritance pattern.
      Mutations in two genes, endoglin and ALK-1, are known to cause HHT, both of which
      mediate signaling by transforming growth factor beta ligands in vascular
      endothelial cells. Ten patients were analyzed. Diagnosis of HHT was carried out
      by means of family history, recurrent bleeding, and the presence of multiple
      telangiectases lesions. Conformation-sensitive gel electrophoresis analyses with
      consistent abnormal migration patterns were cloned and sequenced using the
      MegaBace 1000 DNA automated analyzer. Three novel mutations were identified in
      the coding sequence of the ALK-1 gene in five patients and their families, which
      demonstrated clinical manifestations of HHT type 2. These mutations included a G
      insertion and a T deletion of single base pairs in exons 3 and 7, as well as
      missense mutations in exons 7 and 8 of the ALK-1 gene. These data indicate that
      loss-of-function mutations in a single allele of the ALK1 locus are sufficient to
      contribute to defects in maintaining endothelial integrity. We suggest the high
      rate of mutation detection and the small size of the ALK-1 gene make genomic
      sequencing a viable diagnostic test for HHT2.

PMID- 17219010
TI  - Effect of sodium chloride on the response of the halophyte species Sesuvium
      portulacastrum grown in mannitol-induced water stress.
AB  - Sesuvium portulacastrum is a halophytic species well adapted to salinity and
      drought. In order to evaluate the physiological impact of salt on water deficit
      induced stress response, we cultivated seedlings for 12 days, in the presence or
      absence of 100 mmol l(-1) NaCl, on a nutrient solution containing either 0 mmol
      l(-1) or 25 mmol l(-1) mannitol. Mannitol-induced water stress reduced growth,
      increased the root/shoot ratio, and led to a significant decrease in water
      potential and leaf relative water content, whereas leaf Na(+) and K(+)
      concentrations remained unchanged. The addition of 100 mmol l(-1) NaCl to 25 mmol
      l(-1) mannitol-containing medium mitigated the deleterious impact of water stress
      on growth of S. portulacastrum, improved the relative water content, induced a
      significant decrease in leaf water potential and, concomitantly, resulted in
      enhancement of overall plant photosynthetic activity (i.e. CO(2) net assimilation
      rate, stomatal conductance). Presence of NaCl in the culture medium, together
      with mannitol, significantly increased the level of Na(+) and proline in the
      leaves, but it had no effect on leaf soluble sugar content. These findings
      suggest that the ability of NaCl to improve plant performance under mannitol
      induced water stress may be due to its effect on osmotic adjustment through Na(+)
      and proline accumulation, which is coupled with an improvement in photosynthetic
      activity. A striking recovery in relative water content and growth of the
      seedlings was also recorded in the presence of NaCl on release of the water
      stress induced by mannitol.

PMID- 17219011
TI  - Comparison between sonodynamic effect with protoporphyrin IX and hematoporphyrin
      on sarcoma 180.
AB  - PURPOSE: The comparison between sonodynamic antitumor effect with protoporphyrin
      IX (PPIX) and hematoporphyrin (Hp) at a concentration of 5 mg/kg on Sarcoma 180
      (S180) cells was studied in vivo, and the potential cell damage mechanism was
      also investigated. METHODS: The sonodynamically induced anti-tumor effect of PPIX
      was studied in mice bearing S180 solid tumors. In order to determine the optimum
      timing of ultrasound exposure after administration of PPIX, the PPIX
      concentrations in plasma, skin, muscle and tumor were determined by the
      fluorescence intensity of tissue extractions with a fluorescence
      spectrophotometer based on the standard curve. Anti-tumor effects were estimated
      by measuring the tumor size and the tumor weight. Additionally, the morphological
      changes of S180 cells were evaluated by transmission electron microscope (TEM)
      observation immediately after sonodynamic therapy (SDT) treatment. RESULTS: A
      time of 24 h after the intravenous administration of PPIX was chosen as the best
      time for ultrasound exposure. The antitumor effect induced by PPIX mediated
      sonodynamic therapy (PPIX-SDT) was in a dose dependent manner when ultrasound
      intensity was at or above the inertial cavitation threshold (5 W/cm(2)). A
      significant tumor growth delay was observed both in PPIX mediated sonodynamic
      therapy and in Hp mediated sonodynamic therapy treatments (Hp-SDT), and the tumor
      weight inhibition ratios after the synergistic treatments were 42.82 +/- 0.03 and
      35.22 +/- 0.03%, respectively, this difference was significant at P < 0.05. While
      ultrasound alone (5 W/cm(2)) showed a slight tumor growth inhibitory effect
      compared with the control group, and PPIX or Hp alone showed almost no
      significant effect. Furthermore, TEM observation indicated cell damage was more
      serious in PPIX-SDT treatment group than in Hp-SDT treatment group. After
      sonication, the cell ultra-structure such as cell membrane destruction,
      mitochondria swelling, chromatin condensation might be important factors that
      inhibited the tumor growth and even induced cell death. CONCLUSIONS: The
      comparative results suggested that PPIX as a sonosensitizer might have more
      potential cytotoxicity than Hp when irradiated with ultrasound, and the ultra
      structural changes may account for cell destruction induced by sonodynamic
      therapy in our experiment mode.

PMID- 17219012
TI  - Body mass index and physical activity as risk factors for pancreatic cancer: the
      Multiethnic Cohort Study.
AB  - OBJECTIVE: To examine body mass index (BMI) and physical activity as risk factors
      for pancreatic cancer. METHODS: Eight-year prospective data from 77,255 men and
      90,175 women including 237 and 235 pancreatic cancer cases, respectively, in the
      Hawaii-Los Angeles Multiethnic Cohort Study were analyzed. Participants completed
      a questionnaire that included questions on body weight, height, and physical
      activity. Cox proportional hazards models were calculated to estimate relative
      risks (RR) of pancreatic cancer by levels of BMI and total physical activity (as
      metabolic equivalents (METs)) adjusted for several potential confounders.
      RESULTS: Obesity (BMI > or = 30 kg/m(2)) was associated with an increased
      pancreatic cancer risk in men (RR = 1.51 (95% CI: 1.02-2.26)), but a reduced risk
      in women (RR = 0.65 (95% CI: 0.43-0.99)). In men the risk was higher in never
      smokers than in current or former smokers, though differences were not
      statistically significant. Physical activity was not associated with pancreatic
      cancer risk in either men or women. CONCLUSION: The findings suggest, that a BMI
      of > or = 30 kg/m(2) may be a risk factor for pancreatic cancer in men. No
      evidence of an effect of physical activity on risk was found.

PMID- 17219013
TI  - Quality of race, Hispanic ethnicity, and immigrant status in population-based
      cancer registry data: implications for health disparity studies.
AB  - Population-based cancer registry data from the Surveillance, Epidemiology, and
      End Results (SEER) Program at the National Cancer Institute are based on medical
      records and administrative information. Although SEER data have been used
      extensively in health disparities research, the quality of information concerning
      race, Hispanic ethnicity, and immigrant status has not been systematically
      evaluated. The quality of this information was determined by comparing SEER data
      with self-reported data among 13,538 cancer patients diagnosed between 1973-2001
      in the SEER--National Longitudinal Mortality Study linked database. The overall
      agreement was excellent on race (kappa = 0.90, 95% CI = 0.88-0.91), moderate to
      substantial on Hispanic ethnicity (kappa = 0.61, 95% CI = 0.58-0.64), and low on
      immigrant status (kappa = 0.21. 95% CI = 0.10, 0.23). The effect of these
      disagreements was that SEER data tended to under-classify patient numbers when
      compared to self-identifications, except for the non-Hispanic group which was
      slightly over-classified. These disagreements translated into varying racial-,
      ethnic-, and immigrant status-specific cancer statistics, depending on whether
      self-reported or SEER data were used. In particular, the 5-year Kaplan-Meier
      survival and the median survival time from all causes for American Indians/Alaska
      Natives were substantially higher when based on self-classification (59% and 140
      months, respectively) than when based on SEER classification (44% and 53 months,
      respectively), although the number of patients is small. These results can serve
      as a useful guide to researchers contemplating the use of population-based
      registry data to ascertain disparities in cancer burden. In particular, the study
      results caution against evaluating health disparities by using birthplace as a
      measure of immigrant status and race information for American Indians/Alaska
      Natives.

PMID- 17219014
TI  - Glycemic load, glycemic index, and carbohydrate intake in relation to pancreatic
      cancer risk in a large US cohort.
AB  - BACKGROUND: Consumption of diets with high glycemic load has been hypothesized to
      increase pancreatic cancer risk by raising postprandial glucose levels and
      insulin secretion. METHODS: The authors analyzed data from the American Cancer
      Society Cancer Prevention Study II (CPS-II) Nutrition Cohort to examine the
      association between pancreatic cancer and glycemic load, glycemic index (GI), and
      intake of carbohydrates. Diet was assessed among 124,907 men and women who were
      cancer-free and non-diabetic at baseline in 1992 using a validated 68-item food
      frequency questionnaire (FFQ). During 9 years of follow-up, 401 incident
      pancreatic cancer cases were identified. Cox proportional hazards modeling was
      used to compute hazard rate ratios (RR) adjusted for potential confounding
      factors. RESULTS: We found no association between glycemic load, GI, or
      carbohydrate intake and risk of pancreatic cancer in this population. The hazard
      rate ratio (RR) was 1.01 (95% CI 0.75-1.37, trend P=0.80) for glycemic load, 0.92
      (95% CI 0.68-1.24) for GI, and 1.10 (95% CI 0.80-1.51) for carbohydrate intake
      among men and women in the highest quintile compared to the lowest quintile of
      each measure. We also found no significant association between these measures and
      pancreatic cancer risk among individuals who show a greater susceptibility
      towards insulin insensitivity, such as those who are overweight or more
      sedentary. CONCLUSION: Overall, our data do not support the hypothesis that
      glycemic load or index, or carbohydrate intake are associated with a substantial
      increase in pancreatic cancer risk; however, a weak positive association cannot
      be ruled out.

PMID- 17219015
TI  - Pathology and immunology of lupus glomerulonephritis: can we bridge the two?
AB  - Aberrant immune responses underwrite lupus glomerulonephritis and may contribute
      to glomerular cell proliferation and inflammation. Recent studies provide
      evidence that apoptotic immune cells may initiate immune events leading to tissue
      damage. Nucleosomes within apoptotic particles are recognized by B cells and
      other antigen presenting cells and represent the most likely inciting antigen for
      autoantibody production. Some of these antibodies are nephritogenic depending on
      fine structural composition and antigen recognition in the circulation or on
      renal cells. Deficient complement components contribute to reduced clearance of
      circulating and native kidney apoptotic cells. This review summarizes current
      concepts in lupus immune pathogenesis and attempts to bridge immunology to
      pathology of lupus glomerulonephritis.

PMID- 17219016
TI  - No evidence for preferential transmission of common valine allele of the Val66Met
      polymorphism of the brain-derived neurotrophic factor gene (BDNF) in ADHD.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a highly heritable common
      neurodevelopmental disorder with onset in childhood. A coding SNP (rs6265,
      Val66Met) of the brain-derived neurotrophic factor gene (BDNF) has recently been
      associated with ADHD. More specifically, paternal over-transmission of the common
      Val66 allele to affected children had been observed. We aimed to confirm these
      findings in a large, sufficiently powered, and well characterized German ADHD
      family sample. The Val66Met polymorphism of BDNF was genotyped in 294 families
      comprising one or more affected sibs (468 children). Contrary to previous
      reports, we did not observe over-transmission of the common Val66 allele, from
      either parent to affected children. We did not find support for an involvement of
      the Val66 allele of the Val66Met polymorphism of BDNF in the pathogenesis of ADHD
      in our sample.

PMID- 17219017
TI  - Reduced expression of human endogenous retrovirus (HERV)-W GAG protein in the
      cingulate gyrus and hippocampus in schizophrenia, bipolar disorder, and
      depression.
AB  - The human endogenous retrovirus (HERV)-W multicopy family was identified in human
      DNA from the previously characterized multiple sclerosis associated retroviral
      element (MSRV). Upregulation of the HERV-W POL has been reported in cerebrospinal
      fluid of patients with schizophrenia. The expression of capsid (GAG) protein of
      HERV-W was studied by immunohistochemistry and western blotting in postmortem
      brain tissue of the anterior cingulate cortex and hippocampal formation of normal
      controls and of patients with schizophrenia, bipolar disorder and major
      depression. A physiological expression of GAG protein was detected in neurons as
      well as astroglial cells in normal brain both in the anterior cingulate cortex
      and in the hippocampal formation. There was a statistically significant reduction
      of this expression in neurons and astroglial cells in brains from individuals
      with schizophrenia, major depression, and bipolar disorder. The results from the
      present study confirm that GAG protein encoded by the HERV-W multicopy gene
      family is expressed in cells of the central nervous system under normal
      conditions. Our findings of a cell type-, brain region- and disease-specific
      reduced expression in schizophrenia, major depression, and bipolar disorder are
      compatible with a pathophysiological role of HERVs in human brain disorders. The
      causes and biological consequences of this differential regulation will be the
      subject of further investigations.

PMID- 17219018
TI  - Detection of two porcine circovirus type 2 genotypic groups in United States
      swine herds.
AB  - In late 2005, sporadic cases of an acute onset disease of high mortality were
      observed in 10- to 16-week-old growing pigs among several swine herds of the
      United States. Tissues from the affected pigs in Kansas, Iowa, and North Carolina
      were examined, and porcine circovirus type 2 (PCV2) was detected consistently
      among these tissues. Phylogenetically, PCV2 can be divided into two major
      genotypic groups, PCV2-group 1 and PCV2-group 2. Whereas PCV2-group 1 isolates
      were detected in all the diseased animals, only two of the diseased animals
      harbored PCV2-group 2 isolates. This observation is important because PCV2-group
      1 isolates had never been reported in the United States before (GenBank as of May
      16, 2006), and they are closely related to the PCV2-group 1 isolates that have
      been described in Europe and Asia, previously. Our analysis revealed that each
      genotypic group contains a distinct stretch of nucleotide or amino acid sequence
      that may serve as a signature motif for PCV2-group 1 or PCV2-group 2 isolates.

PMID- 17219019
TI  - Biological polyamines inhibit nucleic-acid-induced polymerisation of prion
      protein.
AB  - Nucleic-acid-induced polymerisation of prion protein, when monitored by anilino
      naphthalene sulfonic acid dye, shows, successively, an immediate fluorescence
      increase of the dye upon mixing of the reactants, followed by a lag period in
      which the dye fluorescence remains unchanged, and then a phase in which dye
      fluorescence increases with time. The biological polyamines spermine and
      spermidine reduce the extent of the initial fluorescence increase, increase the
      lag period, and reduce both the rate and the extent of increase in fluorescence
      intensity of the dye in the final phase of the reaction. Spermidine is less
      effective than spermine in all of these processes. A nearly fivefold lower
      concentration of spermine can inhibit polymerisation of prion protein by tRNAs
      compared to the same process induced by double-stranded nucleic acid. The change
      in the secondary structure of the globular domain of the protein induced by
      nucleic acid is reversed by the addition of spermine, and it prevents structural
      destabilization of this domain induced by nucleic acids. It is suggested that
      physiological event(s) that would reduce the concentrations of intracellular
      biological amines may make nucleic acid available to induce oligomerization and
      polymerisation of cellular prion protein related to prion disease.

PMID- 17219020
TI  - Serological and molecular variability of watermelon mosaic virus (genus
      Potyvirus).
AB  - Watermelon mosaic virus (WMV, genus Potyvirus) is very common in cucurbits
      worldwide, but its variability has been little studied. In France, where WMV has
      been known since 1974, unusually severe symptoms on zucchini squash have been
      found to be associated with WMV since 1999. We have developed serological and
      molecular tools to study WMV variability and the origin of severe strains. Eight
      monoclonal antibodies were obtained, characterized by epitope mapping, and used
      to assess the serological variability of 42 isolates from different countries.
      Sequence analysis based on the NIb-CP region revealed an important variability,
      with three distinct molecular groups. These analyses also suggested frequent
      intraspecific recombination in WMV.

PMID- 17219021
TI  - Tumor necrosis factor blockade in the management of children with orphan
      diseases.
AB  - Tumor necrosis factor (TNF) blockade has been used successfully to treat a number
      of rheumatic disorders that have a substantial burden of illness. In children,
      the TNF antagonists are used mainly for the treatment of juvenile idiopathic
      arthritis (JIA). There are, however, a variety of rare systemic inflammatory
      diseases, in which TNF blockade appears promising. Preliminary data in adults
      suggest that several forms of vasculitis appear to be responsive to TNF
      antagonists-Behcet's disease, polyarteritis nodosa, Wegener granulomatosis, among
      others. Some of them respond better to infliximab, a chimeric monoclonal anti-TNF
      antibody, than to etanercept, a recombinant p75 TNF receptor. We describe our
      limited experience with infliximab in the treatment of three children with rare
      vasculitic conditions.

PMID- 17219022
TI  - Telomeres and aging-related meiotic dysfunction in women.
AB  - Meiotic dysfunction increasingly afflicts women as they age, resulting in
      infertility, miscarriage and handicapped offspring. How aging disrupts meiotic
      function in women remains unclear, but as women increasingly delay childbearing,
      this issue becomes urgent. Telomeres, which mediate aging in mitotic cells, may
      also mediate aging during meiosis. Telomeres shorten during DNA replication. In
      mammals, oocytes remain quiescent, but their precursors replicated during fetal
      oogenesis. Moreover, eggs ovulated from older women entered meiosis later during
      fetal oogenesis than eggs ovulated when younger, and therefore underwent more
      replications. Telomeres also shorten from reactive oxygen, which triggers a DNA
      repair response, so the prolonged interval between fetal oogenesis and ovulation
      in some women would further shorten telomeres. Mice normally do not exhibit age
      related meiotic dysfunction (interestingly, their telomeres are manyfold longer
      than telomeres in women), but genetic or pharmacologic shortening of mouse
      telomeres recapitulates the reproductive aging phenotype of women. This has led
      to a telomere theory of age-related meiotic dysfunction in women, and underlined
      the importance to human health of a mechanistic understanding of telomeres and
      meiosis.

PMID- 17219023
TI  - Regulation of telomere movement by telomere chromatin structure.
AB  - Beyond their role in replication and chromosome end capping, telomeres are also
      thought to function in meiotic chromosome pairing, meiotic and mitotic chromosome
      segregation as well as in nuclear organization. Observations in both somatic and
      meiotic cells suggest that the positioning of telomeres within the nucleus is
      highly specific and believed to be dependent mainly on telomere interactions with
      the nuclear envelope either directly or through chromatin interacting proteins.
      Although little is known about the mechanism of telomere clustering, some studies
      show that it is an active process. Recent data have suggested a regulatory role
      for telomere chromatin structure in telomere movement. This review will summarize
      recent studies on telomere interactions with the nuclear matrix, telomere
      chromatin structure and factors that modify telomere chromatin structure as
      related to regulation of telomere movement.

PMID- 17219024
TI  - Telomeres in meiotic recombination: the yeast side story.
AB  - The aim of this review is threefold. First, we want to report on recent
      observations on the role of telomeres in the alignment of homolog and non
      homologues in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe
      and the relationship of early telomere clustering to later recombination events.
      Second, we compare the similarities and differences between synaptic and
      asynaptic yeasts. Third, we report on the increasing evidence of the effect of
      meiosis on telomeric sequences that suggest an induction of a specific form of
      recombination processes termed telomere rapid deletion.

PMID- 17219026
TI  - Telomeres and meiosis in health and disease.

PMID- 17219025
TI  - Telomere attachment and clustering during meiosis.
AB  - Telomeres are important segments of chromosomes that protect chromosome ends from
      nucleolytic degradation and fusion. At meiosis telomeres display an unprecedented
      behavior which involves their attachment and motility along the nuclear envelope.
      The movements become restricted to a limited nuclear sector during the so-called
      bouquet stage, which is widely conserved among species. Recent observations
      suggest that telomere clustering involves actin and/or microtubules, and is
      altered in the presence of impaired recombinogenic and chromosome related
      functions. This review aims to provide an overview of what is currently known
      about meiotic telomere attachment, dynamics and regulation in synaptic meiosis.

PMID- 17219028
TI  - Concentrations of metals in water, sediment, biofilm, benthic macroinvertebrates,
      and fish in the Boulder River watershed, Montana, and the role of colloids in
      metal uptake.
AB  - To characterize the partitioning of metals in a stream ecosystem, concentrations
      of trace metals including As, Cd, Cu, Pb, and Zn were measured in water,
      colloids, sediment, biofilm (also referred to as aufwuchs), macroinvertebrates,
      and fish collected from the Boulder River watershed, Montana. Median
      concentrations of Cd, Cu, and Zn in water throughout the watershed exceeded the
      U.S. EPA acute and chronic criteria for protection of aquatic life.
      Concentrations of As, Cd, Cu, Pb, and Zn in sediment were sufficient in the
      tributaries to cause invertebrate toxicity. The concentrations of As, Cu, Cd, Pb,
      and Zn in invertebrates from lower Cataract Creek (63, 339, 59, 34, and 2,410
      microg/g dry wt, respectively) were greater than the concentrations in
      invertebrates from the Clark Fork River watershed, Montana (19, 174, 2.3, 15, and
      648 microg/g, respectively), that were associated with reduced survival, growth,
      and health of cutthroat trout fed diets composed of those invertebrates. Colloids
      and biofilm seem to play a critical role in the pathway of metals into the food
      chain and concentrations of As, Cu, Pb, and Zn in these two components are
      significantly correlated. We suggest that transfer of metals associated with Fe
      colloids to biological components of biofilm is an important pathway where metals
      associated with abiotic components are first available to biotic components. The
      significant correlations suggest that Cd, Cu, and Zn may move independently to
      biota (biofilm, invertebrates, or fish tissues) from water and sediment. The
      possibility exists that Cd, Cu, and Zn concentrations increase in fish tissues as
      a result of direct contact with water and sediment and indirect exposure through
      the food chain. However, uptake through the food chain to fish may be more
      important for As. Although As concentrations in colloids and biofilm were
      significantly correlated with As water concentrations, As concentrations in fish
      tissues were not correlated with water. The pathway for Pb into biological
      components seems to begin with sediment because concentrations of Pb in water
      were not significantly correlated with any other component and because
      concentrations of Pb in the water were often below detection limits.

PMID- 17219027
TI  - Noninvasive cerebral oximeter as a surrogate for mixed venous saturation in
      children.
AB  - We evaluated the relationship between regional cerebral oxygen saturation
      (rSO(2)) measured by near-infrared spectroscopy (NIRS) cerebral oximeter with
      superior vena cava (SVC), inferior vena cava (IVC), right atrium (RA), and
      pulmonary artery (PA) saturation measured on room air and 100% inspired oxygen
      administered via a non-rebreather mask (NRB) in children. Twenty nine pediatric
      post-orthotopic heart transplant patients undergoing an annual myocardial biopsy
      were studied. We found a statistically significant correlation between rSO(2) and
      SVC saturations at room air and 100% inspired oxygen concentration via NRB (r =
      0.67, p = 0.0002 on room air; r = 0.44, p = 0.02 on NRB), RA saturation (r =
      0.56, p = 0.002; r = 0.56, p = 0.002), and PA saturation (r = 0.67, p < 0.001; r
      = 0.4, p = 0.03). A significant correlation also existed between rSO(2) and
      measured cardiac index (r = 0.45, p = 0.01) and hemoglobin levels (r = 0.41, p =
      0.02). The concordance correlations were fair to moderate. Bias and precision of
      rSO(2) compared to PA saturations on room air were -0.8 and 13.9%, and they were
      2.1 and 15.6% on NRB. A stepwise linear regression analysis showed that rSO(2)
      saturations were the best predictor of PA saturations on both room air (p =
      0.0001) and NRB (p = 0.012). In children with biventricular anatomy, rSO(2)
      readings do correlate with mixed venous saturation.

PMID- 17219029
TI  - Update on the diagnosis and management of trigemino-autonomic headaches.
AB  - Severe shortlasting headaches are rare but very disabling conditions with a major
      impact on the patients' quality of life. Following the IHS criteria, these
      headaches broadly divide themselves into those associated with autonomic
      symptoms, so called trigeminal autonomic cephalgias (TACs), and those with few
      autonomic symptoms. The trigeminal-autonomic cephalgias include cluster headache,
      paroxysmal hemicranias, and a syndrome called SUNCT (short lasting unilateral
      neuralgic cephalgias with conjunctival injection and tearing). In all of these
      syndromes, hemispheric head pain and cranial autonomic symptoms are prominent.
      The paroxysmal hemicranias have, unlike cluster headaches, a very robust response
      to indomethacin, leading to a notion of indomethacin-sensitive headaches.
      Although TACs are, in comparison with migraine, quite rare, it is nevertheless
      very important to consider the clinical factor that they are easy to diagnose and
      the treatment is very effective in most patients.

PMID- 17219030
TI  - News on the genetics, epidemiology, medical care and translational research of
      Schwannomas.
AB  - Recent years have seen substantial news and updates in the genetics and diagnosis
      of schwannomas, even a new hereditary disease with schwannomas; Schwannomatosis
      has been defined. These developments have consequently led to better evaluation
      of the incidence of schwannomas. Although there has also been progress in the
      treatment of schwannomas especially in the field of radiation therapy, hereditary
      diseases with multiple tumours still represent a therapeutic dilemma. NF2 in
      particular still causes major morbidity and mortality owing to the neurological
      deficit of multiple tumour disease and deafness caused by vestibular nerve
      involvement. Thus there has been great enthusiasm about disease models in the
      hope that translational research will give rise to new therapies.

PMID- 17219031
TI  - Axonal protection achieved in a model of multiple sclerosis using lamotrigine.
AB  - Axonal degeneration is a major cause of permanent disability in multiple
      sclerosis (MS). Recent observations from our and other laboratories suggest that
      sodium accumulation within compromised axons is a key, early step in the
      degenerative process, and hence that limiting axonal sodium influx may represent
      a mechanism for axonal protection in MS. Here we assess whether lamotrigine, a
      sodium channel-blocking agent, is effective in preventing axonal degeneration in
      an animal model of MS, namely chronic-relapsing experimental autoimmune
      encephalomyelitis (CR-EAE). When administered from 7 days post-inoculation,
      lamotrigine provided a small but significant reduction in the neurological
      deficit present at the termination of the experiments (averaged over three
      independent experiments; vehicle: 3.5+/-2.7; lamotrigine: 2.6+/-2.0, P<0.05) and
      preserved more functional axons in the spinal cord (measured as mean compound
      action potential area; vehicle: 31.7 microV.ms+/-23.0; lamotrigine: 42.9+/-27.4,
      P<0.05). Histological examination of the thoracic spinal cord (n=71) revealed
      that lamotrigine treatment also provided significant protection against axonal
      degeneration (percentage degeneration in dorsal column; vehicle: 33.5 %+/-38.5;
      lamotrigine: 10.4 %+/-12.5, P<0.01). The findings suggest that lamotrigine may
      provide a novel avenue for axonal protection in MS.

PMID- 17219032
TI  - Reasons to withhold intra-arterial thrombolysis in clinical practice.
AB  - BACKGROUND: In selected stroke centers intra-arterial thrombolysis (IAT) is used
      for the treatment of acute stroke patients presenting within 6 hours of symptom
      onset. However, data about eligibility of acute stroke patients for IAT in
      clinical practice are very scarce. METHODS: We collected prospectively data on
      indications advising for or against IAT of 230 consecutive stroke patients in a
      tertiary stroke center. RESULTS: 76 patients (33.0%) presented within 3 hours, 69
      (30%) between 3 and 6 hours of symptom onset and 85 (37%) later than 6 hours.
      Arteriography was performed in 71 patients (31%) and IAT in 46 (20%). In 11
      patients no or only peripheral branch occlusions were seen on arteriography and
      therefore IAT was not performed. In 9 patients the ICA was occluded and barred
      IAT and in five anatomical or technical difficulties made IAT impossible. 72
      patients presenting within 6 hours did not undergo arteriography and
      thrombolysis, mostly because of mild (n=44) or rapidly improving neurological
      deficits (n=13). Other reasons to withhold IAT were CT and/or clinical findings
      suggesting lacunar stroke due to small vessel occlusion (n=7), limiting
      comorbidty (n=7) and baseline international normalized ratio>1.7 (n=1).
      CONCLUSIONS: A third of the patients underwent diagnostic arteriography and one
      fifth received IAT. The most important reasons to withhold thrombolysis were
      presentation beyond the 6 hours time window and mild or rapidly improving
      symptoms.

PMID- 17219033
TI  - Contrast-enhanced ultrasound in dermatomyositis- and polymyositis.
AB  - OBJECTIVE: To evaluate prospectively contrast-enhanced ultrasound (CEUS) in
      patients suspected of having dermatomyositis or polymyositis. METHODS: In 35
      patients (23 women, 12 men; mean age, 51 years+/-16 years) who were suspected of
      having dermatomyositis or polymyositis, perfusion in clinically affected skeletal
      muscles was quantified with contrast-enhanced intermittent power Doppler
      ultrasound. By applying a modified model that analyzed the replenishment kinetics
      of microbubbles, the perfusion-related parameters blood flow, local blood volume
      and blood flow velocity were measured. Findings were compared with muscle biopsy
      appearances and with the results of MRI that was performed with a 1.5-Tesla unit.
      Receiver operating characteristic analysis was performed and optimum thresholds
      for diagnosis of myositis were determined. RESULTS: Eleven patients had
      histologically confirmed dermatomyositis or polymyositis and showed significantly
      higher blood flow velocity (P=.01 for dermato- and P<.001 for polymyositis),
      blood flow (P<.001 for dermato- and polymyositis), and blood volume (P=.007 for
      dermato- and P<.001 for polymyositis) on contrast-enhanced ultrasound than those
      who did not have myositis. An increase in signal intensity on T2-weighted MR
      images was found in all patients with myositis. MRI had a sensitivity,
      specificity, positive (PPV), and negative predicting values (NPV) of 100%, 88%,
      77%, and 100% for diagnosis of myositis, respectively. CEUS blood flow was the
      best ultrasound measure for diagnosis of dermato- or polymyositis with
      sensitivity, specificity, PPV, and NPV of 73%, 91%, 80%, and 88%, respectively.
      CONCLUSIONS: Increased skeletal muscle perfusion measured by CEUS could serve as
      an additional measurer for the diagnosis of an inflammatory myopathy.

PMID- 17219034
TI  - End-of-dose deterioration in non ergolinic dopamine agonist monotherapy of
      Parkinson's disease.
AB  - The study was designed to investigate the possible occurrence of "wearing-off"
      (WO) during dopamine agonist (DA) monotherapy. Sixty patients with "de novo"
      idiopathic PD were randomised into one of two DA monotherapy branches to receive
      oral ropinirole at 15 mg per day, or pramipexole at 2.1 mg per day. DA doses
      could be increased in the following two years but levodopa could not be added
      until the study ended. WO was assessed by self-evaluation charts confirmed by a
      blinded observation of a 30% or greater deterioration in the Unified Parkinson's
      Disease Rating Scale (UPDRS) motor score. Proc Mixed and Kaplan-Meier curves
      evaluated treatment variables as a function of time. T-tests were used to compare
      post-hoc variables reclassified according to WO occurrence. Thirty patients
      received ropinirole, and 30 pramipexole monotherapy. Eighteen patients (30%)
      experienced "wearing-off" 15-21 months after beginning monotherapy. No
      differences were observed between treatments. WO phenomena was observed 3.4+/-0.3
      hours after intake of the morning or afternoon dose and consisted of UPDRS score
      worsening by 11.1+/-2.1 points (69-111% more than "on" score). Statistical
      evaluation gave evidence of differences between patients who experienced WO and
      those who did not: UPDRS motor scores obtained at admission to the study were
      higher (by 3.4+/-0.2 points, p=0.01 t-test) and DA doses at 6-12 months were
      higher in fluctuating patients. UPDRS motor scores deteriorated, however.
      similarly and there were no differences, in UPDRS scores recorded in ON
      conditions, between fluctuating and non-fluctuating patients at the end of the
      study. Our findings provide evidence of WO phenomena in patients with early PD
      receiving non-ergolinic DA monotherapy.

PMID- 17219035
TI  - Malignant posterior cerebral artery infarction.

PMID- 17219036
TI  - Amyotrophic lateral sclerosis in an urban setting: a population based study of
      inner city London.

PMID- 17219037
TI  - Paroxysmal torticollis and blepharospasm following bilateral cerebellar
      infarction.

PMID- 17219038
TI  - Extensive corpus callosum infarction: an uncommon pattern of watershed ischaemia?

PMID- 17219039
TI  - Association of genetically proven Huntington's disease and sporadic amyotrophic
      lateral sclerosis in a 72-year-old woman.

PMID- 17219040
TI  - Fridtjof Nansen (1861-1930).

PMID- 17219044
TI  - Gracilis muscle repair of a postoperative perineal hernia.

PMID- 17219047
TI  - Salvage abdominoperineal resection and perineal wound healing in local recurrent
      or persistent anal cancer.

PMID- 17219048
TI  - Transanal Delorme procedure for treatment of rectocele associated with rectal
      intussusception.

PMID- 17219049
TI  - A decade of breast cancer screening in The Netherlands: trends in the
      preoperative diagnosis of breast cancer.
AB  - PURPOSE: In a prospective, multi-institutional follow-up study we describe the
      trends in the preoperative pathologic confirmation of breast cancer of women who
      underwent breast cancer screening between 1995 and 2005. METHODS: We included all
      women aged 50-75 years who underwent biennial screening mammography in the
      southern breast cancer screening region of the Netherlands between February 13,
      1995 and December 22, 2004. Clinical data, breast imaging reports, biopsy results
      and breast surgery reports were collected of all women with a positive screening
      result. Follow-up lasted through the next biennial screening examination and was
      approximately two years for all referred women. RESULTS: Of 258,900 mammographic
      screening examinations, 3,064 (1.2%) were positive screens. The majority of women
      (92%) were analyzed in four regional hospitals and workup yielded breast cancer
      in 1,332 women. From 1995 to 2005, the percentage of breast cancer cases that
      underwent percutaneous biopsy prior to surgery, increased from 42.4 to 100%. The
      proportion of cancers with a preoperative diagnosis of malignancy by percutaneous
      biopsy, increased from 27.1% in 1995 to 92.7% in 2004. Preoperative breast cancer
      confirmation by fine needle aspiration cytology (FNAC) gradually decreased from
      91.3% to 14.5%, whereas preoperative confirmation by ultrasound guided core
      biopsy (USCB) or stereotactic core needle biopsy (SCNB) increased from 8.7% to
      69.1% and from 0 to 17.4% respectively. CONCLUSIONS: A preoperative diagnosis of
      breast cancer is currently obtained in more than 90% of breast cancer patients.
      The increase in preoperative breast cancer diagnosis through 1995-2004 is
      correlated with the introduction of SNCB and increased use of USCB at the expense
      of FNAC.

PMID- 17219050
TI  - Garlic compounds induced calpain and intrinsic caspase cascade for apoptosis in
      human malignant neuroblastoma SH-SY5Y cells.
AB  - Malignant (N-type) neuroblastoma continues to defy current chemotherapeutic
      regimens. We tested the garlic compounds diallyl sulfide (DAS) and diallyl
      disulfide (DADS) for induction of apoptosis in human malignant neuroblastoma SH
      SY5Y cells. Viability of human primary neurons was unaffected after 24 h
      treatment with 50 and 100 microM DAS and 50 microM DADS but slightly affected
      with 100 microM DADS. Treatment with 50 and 100 microM DAS or DADS significantly
      decreased viability in SH-SY5Y cells. Wright staining showed morphological
      features of apoptosis in SH-SY5Y cells treated with 50 and 100 microM DAS or DADS
      for 24 h. ApopTag assay demonstrated DNA fragmentation in apoptotic cells.
      Apoptosis was associated with an increase in [Ca(2+)](i), increase in Bax:Bcl-2
      ratio, mitochondrial release of cytochrome c, increase in cytosolic Smac/Diablo,
      and down regulation of inhibitor-of-apoptosis proteins and nuclear factor kappa B
      (NFkappaB). Activation of caspase-9 and caspase-3 indicated involvement of
      intrinsic pathway of apoptosis. Calpain and caspase-3 activities produced 145 kD
      spectrin break down product (SBDP) and 120 kD SBDP, respectively. Also, caspase-3
      activity cleaved inhibitor of caspase-activated DNase (ICAD). Results strongly
      suggested that the garlic compounds DAS and DADS suppressed anti-apoptotic
      factors and activated calpain and intrinsic caspase cascade for apoptosis in SH
      SY5Y cells.

PMID- 17219051
TI  - Enhanced CD95-mediated apoptosis contributes to radiation hypersensitivity of NBS
      lymphoblasts.
AB  - The molecular causes for enhanced radiosensitivity of Nijmegen Breakage Syndrome
      cells are unclear, especially as repair of DNA damage is hardly impeded in these
      cells. We clearly demonstrate that radiation hypersensitivity is accompanied by
      enhanced gamma-radiation-induced apoptosis in NBS1 deficient lymphoblastoid cell
      lines. Differences in the apoptotic behavior of NBS1 (-/-) and NBS1 (+/-) cells
      are not due to an altered p53 stabilization or phosphorylation in NBS1 (-/-)
      cells. gamma-radiation-induced caspase-8 activity is increased and visualization
      of CD95 clustering by laser scanning microscopy shows a significant higher
      activation of the death receptor in NBS1 (-/-) cells. Further investigation of
      the molecular mechanisms reveals a role for reactive oxygen species-triggered
      activation of CD95. These results demonstrate that NBS1 suppresses the CD95 death
      receptor-dependent apoptotic pathway after gamma-irradiation and evidence is
      given that this is achieved by regulation of the PI3-K/AKT survival pathway.

PMID- 17219052
TI  - Regulation of the expression of prostate apoptosis response protein 4 (Par-4) in
      rat granulosa cells.
AB  - The par-4 gene, directs the expression of a protein in the rat ventral prostate
      after apoptotic stimuli but not growth stimulatory, growth arresting or necrotic
      signals. Since Par-4 expression appears to be ubiquitous we investigated the
      possibility of Par-4 having a role in the rat ovary granulosa cells apoptotic
      death. Par-4 mRNA was detected by RT-PCR with oligonucleotides designed to prime
      Par-4 leucine zipper in the ovaries of 12 day old rats and reached the higher
      levels in 24 days old rats. In situ hybridization analysis revealed that Par-4
      expression is restricted to granulosa cells. PMSG priming of 24 day old rats for
      2 days greatly reduced Par-4 expression in granulosa cells as determined by in
      situ hybridization, RT-PCR of mRNA and protein immunodetection with Western blot.
      Granulosa cells placed in serum-fee culture, exhibited increased levels of Par-4
      mRNA and protein, in good correlation with the degree of apoptosis. The culture
      induced increases in Par-4 are significantly prevented by FSH. Transient
      transfection of granulosa cells with Par-4 leucine zipper domain that functions
      as a dominant-negative regulator of Par-4 activity resulted in lower rates of
      apoptosis while overexpression of the full length Par-4 counteracted FSH effects
      on apoptosis. Par-4 association with PKCzeta which is supposed to inhibit this
      kinase mediated antiapoptotic way is also prevented by FSH and, FSH antiapoptotic
      effects are counteracted by a PKCzeta specific inhibitor. These findings indicate
      that FSH by suppressing Par-4 expression in the ovary activates PKCzeta-dependent
      antiapoptotic pathway and suggest that Par-4 is part of the mechanism underlying
      granulosa cells apoptotic demise.

PMID- 17219053
TI  - Caspase-3 antisense oligodeoxynucleotides inhibit apoptosis in gamma-irradiated
      human leukemia HL-60 cells.
AB  - To study the inhibitory effects of caspase-3 mRNA antisense oligodeoxynucleotides
      (ASODNs) on apoptosis, we designed four ASODNs targeting different regions of
      caspase-3 mRNA and transfected them into human leukemia HL-60 cells. The
      transfected cells were given 10 Gy gamma-irradiation followed by incubation for
      18 h and measurement of apoptosis and caspase-3 expression. Our results showed
      that ASODN-2 targeting the 5' non-coding region of sites -62 to -46, and ASODN-3
      targeting the 5' coding region of sites -1 to 16, both reduced apoptosis measured
      by gel electrophoresis and flow cytometry. Hoechst 33258 staining and TUNEL assay
      revealed that apoptotic indexes in the ASODN-2 and ASODN-3 groups were
      significantly lower than those in the untransfected and mismatched
      oligodeoxynucleotide (MODN) groups. Immunocytochemistry, Western blotting and RT
      PCR showed that expression levels of caspase-3 protein and mRNA in both ASODN-2
      and ASODN-3 groups were decreased compared with those in the untransfected and
      MODN groups. In conclusion, caspase-3 mRNA ASODNs can inhibit gamma-radiation
      induced apoptosis of HL-60 cells and reduce expression of caspase-3 protein and
      mRNA. The results suggest that antisense approach may be useful for therapeutic
      treatment of certain neurodegenerative diseases in which apoptosis is involved.

PMID- 17219054
TI  - Induction of heme-oxygenase 1 requires the p38MAPK and PI3K pathways and
      suppresses apoptotic cell death following hypericin-mediated photodynamic
      therapy.
AB  - Photodynamic therapy (PDT) is an established anticancer modality utilizing the
      photogeneration of reactive oxygen species (ROS) to kill the cancer cells and
      hypericin is a promising photosensitizer for the treatment of bladder tumors. In
      this paper we characterize the signaling pathways and the mechanisms leading to
      the up-regulation of the antioxidant enzyme heme oxygenase (HO-1) in PDT treated
      cancer cells. We show that PDT engages the p38(MAPK) and PI3K signaling cascades
      for HO-1 induction. p38(MAPK) inhibitors or small interfering RNA (siRNA) for
      p38(MAPK) suppress HO-1 induction after PDT and complete repression is attained
      when p38 and PI3K antagonists are combined. Blocking these signaling pathways
      increases additively the propensity of the cells to undergo PDT-induced
      apoptosis, mirroring the effect of HO-1 silencing. Conversely, increasing HO-1
      protein level by hemin prior to irradiation is cytoprotective. HO-1 stimulation
      by PDT is dependent on transcription and de novo protein synthesis and it is
      preceded by the nuclear accumulation of the Nrf2 transcription factor, which is
      reduced by inhibitors of p38(MAPK) and PI3K. Altogether these results indicate
      that stimulation of HO-1 expression by hypericin-PDT is a cytoprotective
      mechanism governed by the p38(MAPK) and PI3K pathways, likely through the control
      of the nuclear availability of the Nrf2 pool.

PMID- 17219055
TI  - The structure and function of heavy metal transport P1B-ATPases.
AB  - P(1B)-type ATPases transport heavy metals (Cu+, Cu2+, Zn2+, Co2+, Cd2+, Pb2+)
      across membranes. Present in most organisms, they are key elements for metal
      homeostasis. P(1B)-type ATPases contain 6-8 transmembrane fragments carrying
      signature sequences in segments flanking the large ATP binding cytoplasmic loop.
      These sequences made possible the differentiation of at least four P(1B)-ATPase
      subgroups with distinct metal selectivity: P(1B-1): Cu+, P(1B-2): Zn2+, P(1B-3):
      Cu2+, P(1B-4): Co2+. Mutagenesis of the invariant transmembrane Cys in H6, Asn
      and Tyr in H7 and Met and Ser in H8 of the Archaeoglobus fulgidus Cu+-ATPase has
      revealed that their side chains likely coordinate the metals during transport and
      constitute a central unique component of these enzymes. The structure of various
      cytoplasmic domains has been solved. The overall structure of those involved in
      enzyme phosphorylation (P-domain), nucleotide binding (N-domain) and energy
      transduction (A-domain), appears similar to those described for the SERCA Ca2+
      ATPase. However, they show different features likely associated with singular
      functions of these proteins. Many P(1B)-type ATPases, but not all of them, also
      contain a diverse arrangement of cytoplasmic metal binding domains (MBDs). In
      spite of their structural differences, all N- and C-terminal MBDs appear to
      control the enzyme turnover rate without affecting metal binding to transmembrane
      transport sites. In addition, eukaryotic Cu+-ATPases have multiple N-MBD regions
      that participate in the metal dependent targeting and localization of these
      proteins. The current knowledge of structure-function relationships among the
      different P(1B)-ATPases allows for a description of selectivity, regulation and
      transport mechanisms. Moreover, it provides a framework to understand mutations
      in human Cu+-ATPases (ATP7A and ATP7B) that lead to Menkes and Wilson diseases.

PMID- 17219056
TI  - MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities.
AB  - MGMT promoter methylation, which has been correlated with the response to
      alkylating agents, was investigated in a retrospective series of 219
      glioblastomas (GBMs) treated with various modalities. MGMT methylation had no
      impact on survival for the whole group, but showed a significant advantage (17.1
      months vs. 13.1) for patients treated with RT+ adjuvant chemotherapy (relative
      risk of death (RR) = 0.53; P = 0.041), particularly when patients received CT
      during the course of RT (MS = 19.9 months vs. 12.5 months; RR = 0.227, P =
      0.001). This suggests that the prognostic impact of MGMT methylation is dependent
      on therapeutic modalities and schedules. MGMT methylation was not correlated with
      the main molecular alterations, such as 10q loss and p53 expression.

PMID- 17219057
TI  - A longitudinal examination of social support, agreeableness and depressive
      symptoms in chronic kidney disease.
AB  - Research examining the role of social support in patient adjustment to chronic
      illness has been inconsistent suggesting that patient individual differences play
      a moderating role. This study examined the hypothesis that the relationship
      between social support and depressive symptoms would differ as a function of
      individual differences in trait Agreeableness. Fifty-nine patients with chronic
      kidney disease were assessed using the Social Provisions Scale, Beck Depression
      Inventory and NEO-Five-Factor Inventory and were followed-up a year and a half
      later. After controlling for baseline depressive symptoms and clinical
      characteristics, regression analyses revealed a significant interaction between
      social support and Agreeableness predicting change in depressive symptoms.
      Greater social support among individuals high in Agreeableness was associated
      with a decrease in depressive symptoms over time, while support had little effect
      on depression change for individuals low in Agreeableness. These findings
      underscore the importance of individual difference variables in understanding
      adjustment to chronic illness.

PMID- 17219058
TI  - The first year inventory: retrospective parent responses to a questionnaire
      designed to identify one-year-olds at risk for autism.
AB  - The First Year Inventory (FYI) is a parent questionnaire designed to assess
      behaviors in 12-month-olds that suggest risk for an eventual diagnosis of autism.
      We examined the construct validity of the FYI by comparing retrospective
      responses of parents of preschool children with autism spectrum disorders (ASD; n
      = 38), other developmental disabilities (DD; n = 15), and typical development
      (TD; n = 40). Children with ASD were rated at significantly higher risk on the
      FYI than children with DD or TD. The DD group was at intermediate risk, also
      significantly higher than the TD group. These retrospective data strengthen the
      validity of the FYI and have implications for refining the FYI to improve its
      utility for prospective screening of 12-month-olds.

PMID- 17219059
TI  - Stereotyped motor behaviors associated with autism in high-risk infants: a pilot
      videotape analysis of a sibling sample.
AB  - This study examined motor behaviors in a longitudinal cohort of infant siblings
      of children with autism. Stereotypic movements and postures occurring during
      standardized observational assessments at 12 and 18 months were coded from
      videotapes. Participants included eight infant siblings later diagnosed with
      autism spectrum disorder (ASD), a random sample of nine non-diagnosed siblings,
      and 15 controls. Videos were coded blind to diagnostic group. At 12 and 18 months
      the ASD group "arm waved" more frequently and at 18 months, one posture ("hands
      to ears") was more frequently observed in the ASD and non-diagnosed group
      compared to the controls. Overall, the siblings subsequently diagnosed with ASD
      and the comparison groups had considerable overlap in their repertoires of
      stereotyped behaviors.

PMID- 17219061
TI  - Ganoderma lucidum polysaccharide peptide reduced the production of
      proinflammatory cytokines in activated rheumatoid synovial fibroblast.
AB  - The aim of the current study was to elucidate the potential therapeutic effect of
      Ganoderma lucidum polysaccharide peptide (GL-PP) in rheumatoid arthritis (RA).
      The effects of GL-PP on cell proliferation and cytokine production were studied
      in RA synovial fibroblasts (RASF). GL-PP significantly inhibited the
      proliferation of RASF. Following the incubation with GL-PP, production of
      interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 in RASF were
      significantly increased as expressed as percentage change from basal values.
      However, the actual effects were minimal due to the low basal values. When RASF
      were activated by IL-1beta or lipopolysaccharides, IL-8 and MCP-1 production
      increased many folds. GL-PP significantly suppressed their productions. The
      inhibitory effects of GL-PP on cytokine production in RASF were at least in part,
      by inhibiting the nuclear factor-kappa B (NF-kappaB) transcription pathway. Our
      results demonstrated that GL-PP had the unique ability to modulate cytokine
      production in RASF and warrants further investigation into its mechanism of
      action.

PMID- 17219062
TI  - A pilot study of the efficacy of heart rate variability (HRV) biofeedback in
      patients with fibromyalgia.
AB  - Fibromyalgia (FM) is a non-inflammatory rheumatologic disorder characterized by
      musculoskeletal pain, fatigue, depression, cognitive dysfunction and sleep
      disturbance. Research suggests that autonomic dysfunction may account for some of
      the symptomatology of FM. An open label trial of biofeedback training was
      conducted to manipulate suboptimal heart rate variability (HRV), a key marker of
      autonomic dysfunction. METHODS: Twelve women ages 18-60 with FM completed 10
      weekly sessions of HRV biofeedback. They were taught to breathe at their resonant
      frequency (RF) and asked to practice twice daily. At sessions 1, 10 and 3-month
      follow-up, physiological and questionnaire data were collected. RESULTS: There
      were clinically significant decreases in depression and pain and improvement in
      functioning from Session 1 to a 3-month follow-up. For depression, the
      improvement occurred by Session 10. HRV and blood pressure variability (BPV)
      increased during biofeedback tasks. HRV increased from Sessions 1-10, while BPV
      decreased from Session 1 to the 3 month follow-up. CONCLUSIONS: These data
      suggest that HRV biofeedback may be a useful treatment for FM, perhaps mediated
      by autonomic changes. While HRV effects were immediate, blood pressure,
      baroreflex, and therapeutic effects were delayed. This is consistent with data on
      the relationship among stress, HPA axis activity, and brain function.

PMID- 17219063
TI  - Gallstone ileus following endoscopic retrograde cholangiopancreatography and
      endoscopic sphincterotomy.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic
      sphincterotomy (ES) is the treatment of choice for common bile duct (CBD) stones.
      Complication rates of 5-15%, and mortality rates of 1.0% have been reported. We
      report a case of gallstone ileus presenting 12 days after ERCP and ES.

PMID- 17219064
TI  - Methylphenidate-induced autoimmune hepatitis.

PMID- 17219065
TI  - Spontaneous resolution of pancreatic gastric fistula.
AB  - Pancreatic pseudocyst is one of the common complications of acute and chronic
      pancreatitis and has variable natural history. We present a case of spontaneous
      resolution of a pancreatic pseudocyst with gastric connection. This case
      presented a 46-year-old man with a pancreatic pseudocyst resulting from a
      complication of acute pancreatitis. This resolved spontaneously through the
      formation of a fistula between the pseudocyst and stomach. The fistula tract was
      also occluded spontaneously and the patient recovered without any complication or
      need for surgical treatment. The patient has been good progress at a two year
      follow up after spontaneous resolution of the fistula.

PMID- 17219066
TI  - Esophageal mucosal sensitivity: possible links with clinical presentations in
      patients with erosive esophagitis and laryngopharyngeal reflux.
AB  - The goal of this study was to assess whether mucosal sensitivity is related to
      different combinations of symptoms and lesions in laryngopharyngeal reflux (LPR)
      and erosive esophagitis and to determine whether reflux pattern is important in
      the development of the symptoms and lesions of gastroesophageal reflux disease
      (GERD) or LPR. We conducted a prospective study of 55 unselected new patients: 27
      erosive esophagitis patients and 28 LPR patients. The erosive esophagitis group
      had a significantly higher rate of Bernstein test positivity than the LPR group.
      The proportions of patients with pathologic acid reflux at the proximal and
      distal probe were similar in the erosive esophagitis group and in the LPR group.
      These results were inconsistent with the endoscopic findings. Both retrosternal
      heartburn and regurgitation symptoms were higher in erosive esophagitis patients.
      The paucity of classical GERD symptoms and lesions in LPR patients could be
      attributable to mucosal insensitivity but not to reflux pattern.

PMID- 17219067
TI  - Drug-induced liver injury associated with ezetimibe therapy.

PMID- 17219068
TI  - The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver
      disease: a pilot study.
AB  - Nonalcoholic fatty liver disease is an increasingly common condition that may
      progress to hepatic cirrhosis. This pilot study evaluated the effects of a low
      carbohydrate, ketogenic diet on obesity-associated fatty liver disease. Five
      patients with a mean body mass index of 36.4 kg/m(2) and biopsy evidence of fatty
      liver disease were instructed to follow the diet (<20 g/d of carbohydrate) with
      nutritional supplementation for 6 months. Patients returned for group meetings
      biweekly for 3 months, then monthly for the second 3 months. The mean weight
      change was -12.8 kg (range 0 to -25.9 kg). Four of 5 posttreatment liver biopsies
      showed histologic improvements in steatosis (P=.02) inflammatory grade (P=.02),
      and fibrosis (P=.07). Six months of a low-carbohydrate, ketogenic diet led to
      significant weight loss and histologic improvement of fatty liver disease.
      Further research is into this approach is warranted.

PMID- 17219069
TI  - Biomechanical remodeling of the chronically obstructed Guinea pig small
      intestine.
AB  - Small intestinal obstruction is a frequently encountered clinical problem. To
      understand the mechanisms behind obstruction and the clinical consequences, data
      are needed on the relation between the morphologic and biomechanical remodeling
      that takes place in the intestinal wall during chronic obstruction. We sought to
      determine the effect of partial obstruction on mechanical and morphologic
      properties of the guinea pig small intestine. Partial obstruction was created
      surgically in 2 groups of animals living for 2 and 4 weeks. Controls were sham
      operated and lived for 4 weeks. A combined impedance planimetry-high-frequency
      ultrasound system was designed to measure the luminal cross-sectional area and
      wall thickness. These measures were used to compute the circumferential stress
      and strain of the excised intestinal segments. The incremental elastic modulus
      was obtained by using nonlinear fitting of the stress-strain curve. Histologic
      analysis and the measurements of total wall collagen were also performed. The
      luminal cross-sectional area, wall thickness, and elastic modulus in
      circumferential direction increased in a time-dependent manner proximal to the
      obstruction site (P < 0.01), whereas no differences in these parameters were
      found distal to the obstruction site (P > 0.25). The circumferential stress
      strain curves of the proximal segments in 2- and 4-week groups shifted to the
      left, indicating the intestinal wall became stiffer. Histologic examination
      revealed a massive increase in the thickness of the muscle layer especially the
      circular smooth muscle layer (P < 0.05). The collagen content proximal to the
      obstruction site was significantly larger in the partially obstructed animals
      compared to controls (P < 0.05). No difference was found distal to the
      obstruction site. Strong correlation was found between the collagen content and
      the elastic modulus at stress levels of 70 kPa stress (P < 0.01) and 10 kPa (P <
      0.05) proximal to the obstruction site suggesting that the alteration of collagen
      has great impact on the mechanical remodeling. The morphologic and biomechanical
      remodeling likely influence the function of the intestine affected by partial
      obstructed intestine.

PMID- 17219070
TI  - Repeat endoscopy for recurrent iron deficiency anemia: an (un)expected finding
      from southeast Asia.

PMID- 17219071
TI  - Quantifying gastric Helicobacter pylori infection: a comparison of quantitative
      culture, urease breath testing, and histology.
AB  - Although there are several methods to detect Helicobacter pylori infection, there
      is no simple validated test to quantify the density of infection, which is
      believed to play a major role in the pathogenesis of H. pylori-associated
      gastritis and peptic ulceration. The aim of this study was to evaluate and
      compare noninvasive and invasive tests for assessing the level of H. pylori
      infection so as to facilitate the development and clinical testing of new
      antibiotic treatments. Healthy volunteers (n=323) were screened for H. pylori
      infection by serology and, if positive (n=86), invited to undergo (13)C urea
      breath testing (UBT) (n=55). An increase of >2.4 parts per thousand (13)CO(2) at
      15 min compared to baseline was considered a positive test. Total cumulative
      urease activity (mumol) at 60 min was also calculated. UBT-positive subjects
      underwent endoscopy and nine biopsies were obtained from defined sites for
      quantitative culture and histological grading using the modified Sydney System. A
      total of 19 subjects were studied, 4 of whom underwent repeat testing. All
      subjects were positive for H. pylori by serology, UBT, culture, and histology.
      The increase in (13)CO(2) at 30 min correlated with the total cumulative urease
      activity at 60 min (r (2)=0.92, P< 0.0001). Bacterial counts (log cfu/biopsy;
      mean+/-SD) were 3.9+/-0.5, 3.9+/-0.4, and 3.9+/-0.6 at the lesser curve antrum,
      greater curve antrum, and corpus, respectively. There was no significant
      correlation between UBT results and bacterial counts at any biopsy site. Nor was
      there any significant correlation between the histology grading and either the
      UBT or the bacterial counts at any site. This study indicates that there is
      little correlation among the three methods used to measure bacterial burden in H.
      pylori infection. Thus, decrements in bacterial numbers during single-agent
      therapy cannot be measured reliably by UBT and therefore cannot be used to
      evaluate the potential efficacy of novel agents to treat gastric H. pylori
      infection.

PMID- 17219072
TI  - Lamina propria and circulating interleukin-8 in newly and previously diagnosed
      pediatric inflammatory bowel disease patients.
AB  - Dysregulation of interleukin-8 (IL-8) production has been proposed to contribute
      to intestinal inflammation in inflammatory bowel disease (IBD) patients. Previous
      studies, which evaluate adult patients with long-standing or steroid-modulated
      disease, have reported conflicting results regarding the role of IL-8 in IBD
      pathogenesis. The present study evaluates IL-8 in colonic organ cultures and sera
      of newly and previously diagnosed pediatric IBD patients with various degrees of
      histopathologic activity. Colon and terminal ileum biopsies were obtained from 26
      patients with Crohn's disease, 12 with ulcerative colitis, 4 with indeterminate
      colitis, and 12 age-matched normal controls. IBD patients were additionally
      characterized as newly or previously diagnosed. Supernatants from organ-cultured
      lamina propria biopsies and sera were evaluated by ELISA for IL-8 protein. IL-8
      increased with degree of histologic inflammation regardless of diagnosis (no
      pathologic diagnosis, 62.6 ng/ml, interquartile range [IQR] 30.4-94.6 ng/ml;
      mild, 92.0 ng/ml, IQR 21.9-170.0 ng/ml; moderate, 676.2 ng/ml, IQR 46.4-2967.7
      ng/ml; severe, 585.6 ng/ml, IQR 149.7-1602.2 ng/ml; P < 0.01). Lamina propria IL
      8 was significantly elevated in moderately and severely inflamed tissue segments
      (603.26 ng/ml; IQR, 72.15-2240.4 ng/ml) compared to noninflamed and mildly
      inflamed segments (67.70 ng/ml; IQR, 30.38-124.1 ng/ml; P = 0.0009). There was no
      significant trend in IL-8 concentration when compared by clinical diagnosis. No
      significant difference was found in IL-8 concentrations in organ cultures from
      newly diagnosed patients versus those from previously diagnosed patients. There
      was no significant correlation between serum IL-8 concentration and organ culture
      IL-8 concentration. We conclude that higher concentrations of IL-8 are found in
      more histologically inflamed tissue segments from pediatric IBD patients. IL-8
      does not appear to be associated with clinical IBD subtype. IL-8 appears to be an
      integral part of both early and established mucosal inflammation in pediatric IBD
      patients. These findings suggest that IL-8-specific therapies may universally
      modify inflammatory activity in IBD patients.

PMID- 17219073
TI  - Etiologic factors of chronic constipation: review of the scientific evidence.
AB  - Geriatric patient educational material and a general practice review suggest
      insufficient dietary fiber intake, inadequate fluid intake, decrease physical
      activity, side effects of drugs, hypothyroidism, sex hormones and colorectal
      cancer obstruction may play a role in the pathogenesis of constipation. A search
      of recent literature, however, reveals that there is a paucity of evidence-based
      publications that address the etiologic factors of chronic constipation. Much of
      current writings on the subject may be based primarily on myths handed down from
      one generation to the next. In the absence of well-designed studies, there do not
      appear to be sufficient evidence-based information to implicate the above as
      major etiologic factors in the development of chronic constipation. The
      etiological role of each of these factors in the development of chronic
      constipation deserves to be assessed by modern techniques and methodologies.
      Funding agencies including the government and industry sponsors should support
      the development of evidence-based data sets. The understanding of the etiology of
      chronic constipation is the foundation on which cost-effective management
      strategies are to be built.

PMID- 17219074
TI  - Type II hereditary angioedema: presenting as food allergy.

PMID- 17219075
TI  - Pulmonary tumor thrombotic microangiopathy from metastatic gallbladder carcinoma:
      an unusual cause of severe pulmonary hypertension.
AB  - Pulmonary hypertension and cor pulmonale due to tumor emboli causing pulmonary
      tumor thrombotic microangiopathy (PTTM) is rare and extremely difficult diagnosis
      to make prior to death. Pulmonary hypertension due to metastatic tumor emboli
      should be included in the differential diagnosis of various causes of dyspnea in
      patients with a history of cancer or more common causes, including infection,
      thromboembolism, metastasis, adverse effects of drugs, and recurrent effusions.
      We describe a patient with gallbladder carcinoma who presented with progressive
      dyspnea and severe pulmonary hypertension. The etiology was tumor emboli and PTTM
      from gallbladder carcinoma, which remained elusive prior to her death despite
      appropriate clinical investigations and was established on autopsy. To the best
      of our knowledge, this is likely the second reported case of PTTM from metastatic
      gallbladder carcinoma.

PMID- 17219076
TI  - A case of fatal necrotizing pancreatitis: complication of hydrochlorothiazide and
      lisinopril therapy.
AB  - We report a case of fatal necrotizing pancreatitis associated with
      hydrochlorothiazide and lisinopril therapy. A 49-year-old man who presented with
      2 days of abdominal pain and vomiting was found to have severe pancreatitis. The
      patient denied any alcohol use. In addition, abdominal ultrasound examinations
      showed no evidence of cholelithiasis or bile duct dilations. Review of his
      medication history with the family revealed that he was being treated with
      hydrochlorothiazide and lisinopril for hypertension. An exploratory laparotomy
      was performed and revealed no common bile duct stones. Unfortunately, the
      patient's hospital course was complicated with multiple organ failure, which
      resulted in death. To the best of our knowledge, there are only 3 other reported
      cases of hydrochlorothiazide-induced necrotizing pancreatitis reported in the
      literature.

PMID- 17219077
TI  - Imatinib mesylate (gleevec) hepatotoxicity.

PMID- 17219078
TI  - Translation and cultural adaptation of a mental health outcome measure: the BASIS
      R(c).
AB  - Culturally and linguistically appropriate outcome measures are needed to address
      the needs of Latino consumers of mental health services. The revised Behavior and
      Symptom Identification Scale (BASIS-R(c)) is an English-language consumer self
      report measure designed to assess outcome of behavioral health or substance abuse
      treatment. This study sought to develop a culturally and linguistically
      appropriate version of the BASIS-R(c) for Spanish-speaking Latinos. To achieve
      this goal, the English instrument was translated and adapted into Spanish by an
      international bilingual committee and tested in four focus groups and 45
      cognitive interviews with Puerto Ricans, Dominicans, and Mexicans living in the
      United States and Puerto Rico. Focus groups and cognitive interviews provided
      qualitative and quantitative information about the instrument's content and
      format, and respondents' understanding of the instructions, questionnaire items,
      time frame, and response options. Respondents' ratings of the clarity and
      importance of each item were also obtained. Analyses of focus group and cognitive
      interview data identified items that were confusing or difficult for
      participants. Findings suggest that the Spanish version of the BASIS-R(c)
      incorporated the cultural diversity of the three groups of Latinos in this study
      without compromising the validity of the English version of the BASIS.

PMID- 17219080
TI  - Environmental correlates of gambling behavior in urban adolescents.
AB  - The present study considered the relation between adolescent gambling behavior
      and the perceived environment, the component of Jessor and Jessor's (1977)
      Problem Behavior Theory that assesses the ways that adolescents perceive the
      attitudes and behaviors of parents and peers. The predominantly African-American
      sample included 188 sophomores from two urban public high schools. Using the
      South Oaks Gambling Screen-Revised for Adolescents to assess gambling risk, rates
      of both at-risk (20.7%) and problem (12.8%) gambling were found to be high. Boys
      displayed more gambling problems than did girls. The perceived environment
      accounted for significant variance in gambling problems and frequency, with
      proximal components displaying stronger relationships than distal components.
      Perceiving parent gambling and friend models for problem behavior were positively
      correlated with gambling problems, and friend models were positively related to
      gambling frequency. Among girls, family support was positively related to
      gambling problems. Among boys, this relation was negative.

PMID- 17219079
TI  - Parent and child agreement for acute stress disorder, post-traumatic stress
      disorder and other psychopathology in a prospective study of children and
      adolescents exposed to single-event trauma.
AB  - Examining parent-child agreement for Acute Stress Disorder (ASD) and Post
      Traumatic Stress Disorder (PTSD) in children and adolescents is essential for
      informing the assessment of trauma-exposed children, yet no studies have examined
      this relationship using appropriate statistical techniques. Parent-child
      agreement for these disorders was examined by structured interview in a
      prospective study of assault and motor vehicle accident (MVA) child survivors,
      assessed at 2-4 weeks and 6 months post-trauma. Children were significantly more
      likely to meet criteria for ASD, as well as other ASD and PTSD symptom clusters,
      based on their own report than on their parent's report. Parent-child agreement
      for ASD was poor (Cohen's kappa = -.04), but fair for PTSD (Cohen's kappa = .21).
      Agreement ranged widely for other emotional disorders (Cohen's kappa = -.07-.64),
      with generalised anxiety disorder found to have superior parent-child agreement
      (when assessed by phi coefficients) relative to ASD and PTSD. The findings
      support the need to directly interview children and adolescents, particularly for
      the early screening of posttraumatic stress, and suggest that other anxiety
      disorders may have a clearer presentation post-trauma.

PMID- 17219081
TI  - Mitochondrial DNA distinction of northeastern China roe deer, Siberian roe deer,
      and European roe deer, to clarify the taxonomic status of northeastern China roe
      deer.
AB  - Partial sequences of the mitochondrial control region of northeastern China roe
      deer were analyzed to determine the degree of genetic diversity. Fourteen
      haplotypes were observed. The haplotype diversity was high (h = 0.872),
      nucleotide diversity was medium (p ( i ) = 0.0108), and the average Tamura-Nei
      nucleotide distance among them was 1.9%, indicating that genetic diversity of roe
      deer from northeastern China was relatively high and that the effective
      population size was large historically. To clarify the northeastern China roe
      deer's taxonomic status, these 14 haplotypes were compared with 31 haplotypes
      published in Genbank from Europe, Siberia, and Korea. The average genetic
      distance between haplogroups of northeastern China and European roe deer (5.8%)
      was more than twice that between northeastern China and Siberian roe deer (2.7%),
      indicating sufficient variation to consider roe deer of northeastern China and
      Siberia as a single species (Capreolus pygargus), distinct from European roe deer
      (Capreolus capreolus). This is the first presentation of mtDNA data for roe deer
      in northeastern China, which will be helpful in investigations of genetic
      diversity and clarifications of the taxonomic status of roe deer in the whole of
      China.

PMID- 17219082
TI  - The relationship between gene polymorphism and CRP level in a Chinese Han
      population.
AB  - We investigated the relationships among the +1444C/T polymorphism in the C
      reactive protein (CRP) gene and the concentration of CRP and the risk of coronary
      heart disease. Using polymerase chain reaction-restriction fragment length
      polymorphism, we analyzed the frequency distribution of genotypes and alleles of
      the +1444C/T polymorphism in samples from 128 patients with coronary heart
      disease (coronary stenosis more than 50%) and 119 unrelated normal individuals.
      The plasma levels of CRP and lipids in the subjects were also measured. The
      frequencies of the genotypes were CC 89.1%, CT 10.9%, and TT 0% in patients and
      CC 89.9%, CT 10.1%, and TT 0% in controls. The frequency of allele C was 94.5% in
      patients and 95.0% in controls, and allele T was 5.5% in patients and 5.1% in
      controls. The distribution of genotypes and alleles in the Chinese Han population
      was significantly different from that of the Caucasian population. There were no
      significant differences between frequencies of genotype and allele of controls
      and those of patients (P>0.05), but in controls the concentrations of CRP in the
      CC genotype subgroup were significantly higher than those in the CT genotype
      subgroup (P<0.05). This suggests that the +1444C/T variant in the CRP gene
      influences the basal CRP level in normal people. These findings imply that there
      may eventually be a need to establish genotype-specific risk thresholds of the
      CRP level.

PMID- 17219083
TI  - Computational modeling of factor Xa inhibition by immobilized tissue factor
      pathway inhibitor.
AB  - Coating surfaces of implanted devices with anticoagulants can reduce thrombosis
      and studies using a recombinant form of endogenous tissue factor pathway
      inhibitor (rTFPI) are promising. The anticoagulant function of immobilized rTFPI
      is thought to occur primarily by its inhibition of plasma clotting factor Xa
      (FXa); however the kinetics of this reaction at a surface are as yet unknown. To
      better understand the surface inhibition reaction under flow conditions, a
      theoretical model was developed delineating the roles of mass transport and
      reaction kinetics for an in vitro parallel plate device used in prior
      experimental studies [Hall et al., J. Biomech. Eng. 120:484-490, 1998]. As a
      first approximation, the kinetics of inhibition of FXa by rTFPI reported for
      static, homogeneous systems was considered. The unsteady convection-diffusion
      equation was solved for different wall-shear rates and inlet concentrations of
      FXa using the computational fluid dynamics software CFD-ACE (ESI Software Group).
      The results show that the heterogeneous inhibition reaction is diffusion
      controlled prior to saturation of the rTFPI. The experimental results compare
      favorably with the model at the lower shear rates (100-400 s(-1)). At higher
      shear rates (>400 s(-1)) the theoretical results follow the same trend as the
      experimental results but show a greater inhibition of FXa, implying an effect of
      flow or shear on the inhibition reaction.

PMID- 17219084
TI  - Incorporation of myofilament activation mechanics into a lumped model of the
      human heart.
AB  - The success and usefulness of lumped cardiovascular models are directly dependent
      on the physiological fidelity of their formulation. In most existing lumped
      formulations for the heart, the compliance of the chamber is modeled based on its
      electrical analog, the capacitor. This has traditionally resulted in the use of a
      pre-described time-varying stiffness modulus for simulating the cardiac
      contractions. Unfortunately, such a time-varying stiffness does not include any
      physiological contractile machinery and thus no dependency on fiber sarcomere
      length and intracellular calcium concentrations, key mechanisms responsible for
      proper cardiac function. In this paper a lumped cardiovascular model is presented
      that is based on the incorporation of detailed myofilament activation for
      simulating the ventricular calcium binding and cross-bridging mechanism. Upon
      validation against experimental data, it is shown that the new myofilament
      activation-based model considerably increases the physiological validity and
      internal consistency of the cardiovascular simulations in comparison to the
      traditional variable compliance-based models. It is also shown, through specific
      case studies, that the present model can serve as a quick response tool for
      testing various hypotheses concerning the impact of the calcium binding and
      crossbridge kinetics on the overall performance of the cardiovascular system.

PMID- 17219085
TI  - Sex steroid receptor evolution and signalling in aquatic invertebrates.
AB  - In vertebrate reproductive endocrinology sex steroids play a pivotal role via
      binding to receptors. However, information on the origin and relevance of sex
      steroids in invertebrates is limited. This review highlights current literature
      on steroid receptors in aquatic invertebrates and reports on some new findings.
      It has been shown that invertebrates of the deuterostome clade, such as Acrania
      and Echinodermata, respond to estrogens and androgens and, at least in
      Branchiostoma, an estrogen receptor has been cloned. Within the protostomes, most
      findings are related to aquatic molluscs. Sex steroid receptor-like proteins are
      abundant in gastropods, bivalves and cephalopods and also sex hormone signalling
      shows partial similarity to the deuterostomes. In ecdysozoans, however, the
      impact of sex steroids is still a matter of debate even though there is evidence
      on the presence of estrogen receptor-like proteins in Crustacea and on
      physiological effects of estrogens in both Nematoda and Crustacea. Recent
      findings suggest the presence of an estrogen receptor alpha-like protein of
      unclear physiological role in Gammarus fossarum (Crustacea). Binding studies
      revealed the crustacean Hyalella azteca to possess specific binding sites only
      for androgens but not for estrogens suggesting a possible limitation to
      functional androgen receptors in this species. Further studies have to be
      conducted to shed more light into the discussion about the controversy about sex
      steroid receptors in invertebrates.

PMID- 17219086
TI  - Sex steroids and potential mechanisms of non-genomic endocrine disruption in
      invertebrates.
AB  - The review reports on the presence and metabolism of sex steroids in several
      invertebrate species and provides detailed information on possible mechanisms of
      endocrine disruption other than the interaction with nuclear receptors. The
      presence of most vertebrate sex steroids in invertebrate tissues has been
      demonstrated by liquid or gas chromatography coupled to mass spectrometry. In
      addition, enzymatic pathways involved in the steroidogenic pathway have been
      described in at least some invertebrate phyla. Some endocrine disruptors induce
      alterations in these metabolic pathways and might lead to changes in steroid
      levels. Growing evidence suggests that estradiol can act through non-genomic
      pathways in molluscs, and that xenobiotics can as well interfere in these
      signalling cascades. In spite of these recent advances, most question marks on
      the action and function of sex steroids in invertebrates remain to be answered.

PMID- 17219087
TI  - Endocrine disruption in prosobranch molluscs: evidence and ecological relevance.
AB  - Prosobranch snails represent almost 50% of all recent molluscs, are ubiquitously
      distributed, play important roles in various ecosystems and exhibit a variety of
      reproductive modes and life-cycle-strategies. Many of them attain life spans of
      several years, which in combination with their limited ability to metabolize
      organic chemicals, may contribute to the fact that prosobranchs constitute one of
      the most endangered taxonomic groups in aquatic ecosystems. Although it is not
      yet known to what extent endocrine disrupting chemicals (EDCs) contribute to this
      situation, the case of tributyltin (TBT) and its population-level impact on
      prosobranchs demonstrates the general susceptibility of these invertebrates. The
      existing evidence for comparable population-level effects in prosobranch snails
      by other androgens, antiandrogens, and estrogens is critically reviewed. The
      example of TBT demonstrates the difficulty to prove an endocrine mode of action
      for a given chemical. Although it is generally accepted that TBT causes imposex
      and intersex in prosobranch snails as a result of endocrine disruption, the
      detailed biochemical mechanism is still a matter of debate. The strengths and
      weaknesses of the five competing hypotheses are discussed, together with
      previously unpublished data. Finally, the ecological relevance of EDC effects on
      the population and community level and the application of prosobranchs for the
      assessment of EDCs are addressed.

PMID- 17219088
TI  - Endocrine disruption in nematodes: effects and mechanisms.
AB  - This paper reviews the current knowledge on endocrine disruption in nematodes.
      These organisms have received little attention in the field of ecotoxicology, in
      spite of their important role in aquatic ecosystems. Research on endocrine
      regulation and disruption in nematodes, especially the more recent studies,
      concentrate mainly on one species, Caenorhabditis elegans. Although an endocrine
      system is not known in nematodes, there is evidence that many processes are
      regulated via hormonal pathways. As vertebrate hormones, such as steroids, may
      have endocrine functions in nematodes as well, endocrine disrupting chemicals
      (EDCs) defined for vertebrates may also be able to influence nematodes. The
      studies that are reviewed here, and own data showed that potential EDCs can
      affect nematodes on all organizational levels, from molecules to communities. It
      is concluded that nematodes, notably its prominent species C. elegans, are a
      promising organism group for the development of biomonitoring tools, provided
      that more mechanistic evidence is gathered on hormonal processes within these
      animals.

PMID- 17219089
TI  - Small is useful in endocrine disrupter assessment--four key recommendations for
      aquatic invertebrate research.
AB  - As we enter the 21st "biocentury", with issues such as biodiversity and
      biotechnology growing in public profile, it is important to reflect on the
      immense ecological, medical and economic importance of invertebrates. Efforts to
      understand the diverse biology of invertebrates come from many directions,
      including Nobel Prize winning developmental biology, research to control insects
      that threaten human health and food supplies, aquaculture opportunities and also
      within ecotoxicology. In the latter context, this special journal volume
      highlights the importance of addressing endocrine disruption in aquatic
      invertebrates, from molecular and cellular biomarkers to population-relevant
      adverse effects. The contributors to this special volume have provided an
      excellent assessment of both the fundamental endocrinology and applied
      ecotoxicology of many aquatic invertebrate groups. On the premise that
      reproductive success is ultimately the vital population parameter, this chapter
      gives a personal view of key gaps in knowledge in invertebrate reproductive and
      developmental endocrinology and ecotoxicology. Based on current knowledge, there
      are four key issues that need to be prioritised within aquatic ecotoxicology: (1)
      a wider assessment of the reproductive status of invertebrates in both freshwater
      and coastal ecosystems; (2) prioritisation of laboratory studies in OECD and
      other regulatory test organisms, including basic endocrinology and ADME
      (absorption, distribution, metabolism and excretion) research; (3) development
      and validation of mechanistic biomarkers that can be used as "signposts" to help
      prioritise species and chronic test endpoint selection, and help link data from
      laboratory and field studies; and (4) develop a comparative invertebrate
      toxicology database utilising the prioritised reference chemicals from the EDIETA
      workshop, encompassing the diverse modes-of-action pertinent to endocrine
      disrupter testing in both aquatic arthropod and non-arthropod invertebrates.

PMID- 17219090
TI  - Prosobranch snails as test organisms for the assessment of endocrine active
      chemicals--an overview and a guideline proposal for a reproduction test with the
      freshwater mudsnail Potamopyrgus antipodarum.
AB  - Recently, prosobranch snails have been recommended as promising candidates for
      test organisms for the assessment of endocrine active chemicals. Three
      prosobranch snail species, the freshwater mudsnail Potamopyrgus antipodarum, the
      freshwater ramshorn snail Marisa cornuarietis, and the marine netted whelk
      Nassarius reticulatus are portrayed and their respective biotests are presented
      together with results of laboratory experiments and biological effect monitoring
      surveys in the field. All characterized species are highly sensitive toward xeno
      androgens [triphenyltin (TPT), tributyltin (TBT), methyltestosterone (MT) and
      fenarimol (FEN)], and xeno-estrogens [bisphenol A (BPA), octylphenol (OP),
      ethinylestradiol], and show effects at environmentally relevant, rather low
      concentrations in laboratory experiments. For exposure to the xeno-androgen TPT,
      EC(10) values range between 15.9 and 29.0 ng as Sn/L (sediment 0.03 mug as
      Sn/kg), for TBT, EC(10) values are found between 3.42 and 37.8 ng as Sn/L
      (sediment 2.98 microg as Sn/kg) and effect concentrations for FEN are calculated
      as 18.6 ng/L (EC(10)) and 0.19 microg/kg (EC(50) sediment; EC(10) not
      calculable). Exposure to xeno-estrogens yielded EC(10 )values of 13.9 ng/L (0.19
      microg/kg) for BPA, a NOEC of <1 microg/L (EC(10) of 0.004 microg/kg) for OP and
      a NOEC of 1 ng/l (EC(10) sediment of 2.2 microg/kg) for ethinylestradiol.
      Responses to androgens comprised the development of imposex and the reduction of
      fertility or embryo production, effects of estrogens included the stimulation of
      egg production and embryo production, and the increased weight of glands. Also,
      biological effect monitoring studies with P. antipodarum and N. reticulatus in
      several rivers or estuarine areas revealed the capacity of the biotests to detect
      an androgenic or estrogenic potential of sediment samples. A comparison of the
      three test species with regard to sensitivity and practical aspects in routine
      application favors the freshwater mudsnail P. antipodarum for a standardized
      procedure, and this reproduction test will be introduced into the OECD guideline
      program for standardization in the near future.

PMID- 17219091
TI  - Developing Test Guidelines on invertebrate development and reproduction for the
      assessment of chemicals, including potential endocrine active substances- the
      OECD perspective.
AB  - The Organisation for Economic Co-operation and Development (OECD) Test Guidelines
      Programme is involved in the international harmonization and validation of test
      methods to evaluate effects of chemicals, including potential endocrine active
      substances. To meet their existing and foreseen regulatory needs in this area,
      OECD member countries have encouraged the development of test methods and their
      emergence at the OECD level. Validation activities are underway in countries and
      industry to ascertain the relevance and reliability of these tests to enable
      future regulatory acceptance. This includes work on development and (sexual)
      reproduction of aquatic invertebrates. What is the importance of mechanistic
      information in regulating chemicals, and how to address the issue of possible
      endocrine disruption in invertebrates while integrating these tests in a
      regulatory scheme are the current questions faced by the OECD countries.

PMID- 17219092
TI  - Cloned blastocysts produced by nuclear transfer from somatic cells in cynomolgus
      monkeys (Macaca fascicularis).
AB  - In nonhuman primates (NHPs), there have so far been few reports about nuclear
      transfer (NT), especially using adult somatic cells. The objective of this study
      was to determine the developmental competence of NT embryos derived from various
      somatic cells embryonic stem (ES), amniotic epithelial, cumulus, or fetal
      fibroblast cells] and the nuclear transfer method, such as electro fusion or
      piezo microinjection, activation with chemical reagent [ionomycine/6
      dimethylaminopurine (DMAP), calcium ionophore A23187/DMAP, or cycloheximide
      (CHX)] and reprogramming time (1, 2, or 4 h; in this study, the duration from
      injection or fusion to activation was defined as the reprogramming time). Our
      results showed that a 1-h reprogramming and activation with ionomycin/DMAP are
      suitable for NT in monkeys. Developing cleaved embryos up to the six-cell stage
      was similar among all experiments. However, beyond the eight-cell stage,
      developmental rates were higher in NT embryos reconstructed with fetal fibroblast
      cells and amniotic epithelial cells, and we were able to produce NT blastocysts
      from these cells. Interestingly, electro fusion is sufficient for amniotic
      epithelial cells and piezo microinjection is better suited for fetal fibroblast
      cells to produce NT blastocysts, thus suggesting that the best method for somatic
      cell NT may be different between cell types.

PMID- 17219093
TI  - Copulation behavior within one-male groups of wild Rhinopithecus roxellana in the
      Qinling Mountains of China.
AB  - This study was conducted using focal animal sampling on the west ridge group of
      the Sichuan snub-nosed monkey (Rhinopithecus roxellana) located in the Zhouzhi
      National Nature Reserve on the north slope of the Qinling Mountains, from 8 July
      2003 to 24 May 2004. The difference in the average frequency of copulations for
      each focal male for each month was significant (F=3.068, P=0.016, one-way ANOVA
      test) with the majority of copulations occurring between September and November.
      Duration of intromission ranged from 2 to 39 s, with a mean of 16.0+/-0.4 s.
      Females initiated 627 courtship attempts (96.2%), while males only initiated
      3.8%. Both adult females (72.8%) and sub-adult females (27.2%) were involved in
      sexual interference acts. Females who gave birth in 2004 performed more sexual
      interference acts than would be expected by chance in the reproductive period of
      2003 (X2=13.73>X2(0.005,2), df=2, P<0.005). Male response to female interference
      was equally divided into "solicitor mounting" and "interrupter mounting". The
      resident males of one-male units were not observed to mount both the solicitor
      and the interrupter or mount neither following female solicitation interruptions.
      Three post-conception copulations were also observed in this study. These results
      suggest a skewed sexual competition, with multiple females competing for a single
      male, which was shown by courtship attempts and female interference.

PMID- 17219094
TI  - Features discriminating SARS from other severe viral respiratory tract
      infections.
AB  - This study investigated the discriminatory features of severe acute respiratory
      syndrome (SARS) and severe non-SARS community-acquired viral respiratory
      infection (requiring hospitalization) in an emergency department in Hong Kong. In
      a case-control study, clinical, laboratory and radiological data from 322
      patients with laboratory-confirmed SARS from the 2003 SARS outbreak were compared
      with the data of 253 non-SARS adult patients with confirmed viral respiratory
      tract infection from 2004 in order to identify discriminatory features. Among the
      non-SARS patients, 235 (93%) were diagnosed as having influenza infections
      (primarily H3N2 subtype) and 77 (30%) had radiological evidence of pneumonia. In
      the early phase of the illness and after adjusting for baseline characteristics,
      SARS patients were less likely to have lower respiratory symptoms (e.g. sputum
      production, shortness of breath, chest pain) and more likely to have myalgia (p <
      0.001). SARS patients had lower mean leukocyte and neutrophil counts (p < 0.0001)
      and more commonly had "ground-glass" radiological changes with no pleural
      effusion. Despite having a younger average age, SARS patients had a more
      aggressive respiratory course requiring admission to the ICU and a higher
      mortality rate. The area under the receiver operator characteristic curve for
      predicting SARS when all variables were considered was 0.983. Using a cutoff
      score of >99, the sensitivity was 89.1% (95%CI 82.0-94.0) and the specificity was
      98.0% (95%CI 95.4-99.3). The area under the receiver operator characteristic
      curve for predicting SARS when all variables except radiological change were
      considered was 0.933. Using a cutoff score of >8, the sensitivity was 80.7%
      (95%CI 72.4-87.3) and the specificity was 94.5% (95%CI 90.9-96.9). Certain
      clinical manifestations and laboratory changes may help to distinguish SARS from
      other influenza-like illnesses. Scoring systems may help identify patients who
      should receive more specific tests for influenza or SARS.

PMID- 17219095
TI  - Surface anchorage of superantigen SEA promotes induction of specific antitumor
      immune response by tumor-derived exosomes.
AB  - Tumor-derived exosomes have been regarded as a new kind of cancer vaccine;
      however, their therapeutic efficacy needs to be further improved. Superantigen
      staphylococcal enterotoxin A (SEA)-coated tumor cells have been shown to potently
      induce tumor-specific T cell response. To increase efficacy of tumor-derived
      exosomes to induce antitumor immune response, we modified the exosomes by protein
      transfer of SEA tailed with a highly hydrophobic transmembrane domain (SEA-TM)
      and designated those SEA-TM-anchored exosomes as Exo/SEA-TM. We found the
      exosomes secreted from murine lymphoma E.G7-OVA cell line were round vesicles
      with the sizes of 40-100 nm limited by a bilayer membrane. Interestingly, the
      inner structure of the exosomes were visible under the transmission electron
      microscope; those "honeycomb-like" inner structure has not been described by
      other labs. Immunization with Exo/SEA-TM inhibited tumor growth and prolonged
      survival of the mice challenged with parental tumor cells more significantly than
      with exosomes (Exo) and even more than with the mixture of exosomes and SEA-TM.
      The results of mixed lymphocyte-tumor reaction (MLTR) showed that the increased
      IL-2, IFN-gamma secretion, and specific cytotoxic T lymphocyte (CTL) could be
      effectively induced from the splenic lymphocytes of the mice immunized with
      Exo/SEA-TM. In vivo depletion experiments showed that CD8(+) T cells are the main
      effector cells, and both CD4(+) T cells and NK cells are also involved in the
      antitumor effect of Exo/SEA-TM immunization. Therefore, tumor-derived exosomes
      surface anchored with SEA-TM can efficiently induce tumor-specific CTL thereby
      resulting in more potent inhibition of tumor growth. Our data provide an
      efficient and novel approach to tumor immunotherapy by protein modification of
      tumor-derived exosomes.

PMID- 17219097
TI  - Development and implementation of the CCME Reference Method for the Canada-Wide
      Standard for Petroleum Hydrocarbons (PHC) in soil: a case study.
AB  - Petroleum hydrocarbons have historically been analyzed by a wide variety of test
      methods. Interlaboratory studies have shown that standardization of both
      extraction and gas chromatographic analysis improved interlaboratory variability
      in hydrocarbon analysis. The Canadian Council of Ministers of the Environment has
      required a reference method for use with the Canada-wide standard for petroleum
      hydrocarbons. The process for developing and validating this method is described.
      This method requires the determination of 4 hydrocarbon fractions, namely, F1
      (nC6 to nC10), F2 (>nC10 to nC16), F3 (>nC16 to nC34) and, F4 (nC35+), using GC
      FID or gravimetry. The Tier 1 method was validated in a single laboratory study.
      This validated method was subjected to interlaboratory studies to determine its
      applicability and precision.

PMID- 17219096
TI  - Effect of adenoviral mediated overexpression of fibromodulin on human dermal
      fibroblasts and scar formation in full-thickness incisional wounds.
AB  - Fibromodulin, a member of the small leucine-rich proteoglycan family, has been
      recently suggested as a biologically significant mediator of fetal scarless
      repair. To assess the role of fibromodulin in the tissue remodeling, we
      constructed an adenoviral vector expressing human fibromodulin cDNA. We evaluated
      the effect of adenovirus-mediated overexpression of fibromodulin in vitro on
      transforming growth factors and metalloproteinases in fibroblasts and in vivo on
      full-thickness incisional wounds in a rabbit model. In vitro, we found that Ad
      Fibromodulin induced a decrease of expression of TGF-beta(1) and TGF-beta(2)
      precursor proteins, but an increase in expression of TGF-beta(3) precursor
      protein and TGF-beta type II receptor. In addition, fibromodulin overexpression
      resulted in decreased MMP-1 and MMP-3 protein secretion but increased MMP-2, TIMP
      1, and TIMP-2 secretion, whereas MMP-9 and MMP-13 were not influenced by
      fibromodulin overexpression. In vivo evaluation by histopathology and tensile
      strength demonstrated that Ad-Fibromodulin administration could ameliorate wound
      healing in incisional wounds. In conclusion, although the mechanism of scar
      formation in adult wounds remains incompletely understood, we found that
      fibromodulin overexpression improves wound healing in vivo, suggesting that
      fibromodulin may be a key mediator in reduced scarring.

PMID- 17219098
TI  - Novel approaches to the analysis of steroid estrogens in river sediments.
AB  - A wide range of estrogenic contaminants has been detected in the aquatic
      environment. Among these, natural and synthetic steroid estrogens, typically
      present in municipal sewage-treatment plant (STP) effluents, are the most potent.
      In this study a new GC-MS method has been developed for direct analysis of five
      major steroid estrogens (estrone, 17beta-estradiol, 17alpha-ethinylestradiol,
      dienestrol, and diethylstilbestrol) in river sediments. Four GC-MS systems used
      for analysis of underivatized analytes in purified extracts were compared.
      Relatively low detection limits (1.5-5 ng g(-1) dried sediment) and good
      repeatability of GC splitless injection (RSD 1-2%) were achieved by use of a
      system combining low-pressure gas chromatography with a single-quadrupole mass
      analyzer (LP-GC-MS). Use of orthogonal gas chromatography (GCxGC) hyphenated with
      high-speed time-of-flight mass spectrometry (HSTOF-MS) enabled not only
      significantly better resolution of target analytes, and their unequivocal
      identification, but also further improvement (decrease) of their detection
      limits. In addition to these outcomes, use of this unique GCxGC-TOF-MS system
      enabled identification of several other non-target chemicals, including
      pharmaceutical steroids, present in purified sediment extracts.

PMID- 17219099
TI  - GC-MS-MS analysis of bacterial fatty acids in heavily creosote-contaminated soil
      samples.
AB  - Phospholipid fatty acid profiles of soil samples enable rapid and reproducible
      measurement and characterization of the dominant soil microbial communities. When
      extensive polycyclic aromatic hydrocarbon (PAH) pollution is present in the soil
      it is very difficult, or even impossible, to distinguish specific fatty acids in
      GC-MS chromatograms in full-scan mode, because of the PAHs which, because of
      their lipophilic character, are co-extracted with the lipids. Selected ions in
      the samples were scanned in MS-MS mode to eliminate the aromatic hydrocarbon
      signals and obtain clear chromatograms of the fatty acids. By using this
      technique it was possible to clearly distinguish at least eleven fatty acids in
      heavily creosote-contaminated soil samples (PAH concentration approximately 15 g
      kg(-1) dry weight of soil).

PMID- 17219100
TI  - Development of a novel nitrate-selective composite sensor based on doped
      polypyrrole.
AB  - The manufacture and evaluation of a novel sensor built with a composite material,
      highly selective to nitrate ions using doped polypyrrole as a recognition agent,
      are presented. When the ratio of recognition agent to graphite was optimized at
      1:1, and the sensitivities found closely approached nernstian behavior. The
      stability times attained were less than 14 min with response times also below 20
      s. Batch characterization of the sensor displayed a sensitivity of 57.1 mV/decade
      of nitrate ion activity (alphaNO3-) and a detection limit of 5.37 x 10(-5) M,
      which are comparable to those reported for commercial sensors. Evaluation of the
      selectivity coefficients showed high affinity to nitrate ion, superior to that of
      commercial sensors and others reported in the literature. The composite material
      gives the sensor a prolonged service life with the added capability of allowing
      the regeneration of its active surface. Coupling the sensor and a solid state,
      composite-type, reference electrode to a flow injection analysis system (FIA)
      permitted to achieve an effective overall assessment of the system. A nitrate
      determination test was conducted on real samples. A comparison of the results
      obtained, either with stationary measurements or with FIA, indicated that there
      were no significant differences from the values from manufacturer's
      specifications.

PMID- 17219101
TI  - An improved method for the analysis of volatile polyfluorinated alkyl substances
      in environmental air samples.
AB  - This article describes the optimisation and validation of an analytical method
      for the determination of volatile polyfluorinated alkyl substances (PFAS) in
      environmental air samples. Airborne fluorinated telomer alcohols (FTOHs) as well
      as fluorinated sulfonamides and sulfonamidoethanols (FOSAs/FOSEs) were enriched
      on glass-fibre filters (GFFs), polyurethane foams (PUFs) and XAD-2 resin by means
      of high-volume air samplers. Sensitive and selective determination was performed
      using gas chromatography/chemical ionisation-mass spectrometry (GC/CI-MS). Five
      mass-labelled internal standard (IS) compounds were applied to ensure the
      accuracy of the analytical results. No major blank problems were encountered.
      Recovery experiments were performed, showing losses of the most volatile
      compounds during extraction and extract concentration as well as strong signal
      enhancement for FOSEs due to matrix effects. Breakthrough experiments revealed
      losses of the most volatile FTOHs during sampling, while FOSAs/FOSEs were
      quantitatively retained. Both analyte losses and matrix effects could be
      remediated by application of adequate mass-labelled IS. Method quantification
      limits (MQLs) of the optimised method ranged from 0.2 to 2.5 pg/m(3) for
      individual target compounds. As part of the method validation, an interlaboratory
      comparison of instrumental quantification methods was conducted. The
      applicability of the method was demonstrated by means of environmental air
      samples from an urban and a rural location in Northern Germany.

PMID- 17219102
TI  - Isolation of cold stress-responsive genes in the reproductive organs, and
      characterization of the OsLti6b gene from rice (Oryza sativa L.).
AB  - During their reproductive stage, rice crops often are exposed to cold stress,
      which leads to sterility and reduced yields. To understand the cold response
      mechanism at that stage, we used an mRNA differential display method to isolate
      cold-responsive genes from pre-anthesis flowers. Approximately 5,000 transcripts
      were identified here, of which 123 were found to be displayed differentially
      between the control (30 degrees C) and cold-treated (12 degrees C) flowers. Among
      them, 26 were analyzed by northern analysis; 8 of those clones were confirmed as
      cold-responsive. OsLti6b, encoding a hydrophobic protein homologous to
      Arabidopsis RCI2, was analyzed in detail. RNA blot analysis revealed that its
      transcript is increased by cold, salt, drought, or ABA treatments. In situ
      hybridization indicated that this transcript is highly accumulated in the ovaries
      and stamens of cold-treated flowers, particularly in the anther walls and
      vascular tissues of the filaments. Over-expression of OsLti6b increased cold
      tolerance as revealed by seedling wilting rates and ion leakages of mature
      leaves, demonstrating that the extent of the tolerance correlates well with its
      expression level.

PMID- 17219103
TI  - Overexpression of the chimeric gene of the floral regulator CONSTANS and the EAR
      motif repressor causes late flowering in Arabidopsis.
AB  - The transcription factor CONSTANS (CO) plays a central role in the photoperiod
      pathway by integrating the circadian clock and light signals into a control for
      flowering time. CO induces flowering locus T (FT) and suppressor of
      overexpression of CO 1 (SOC1) expression, and thereby promotes flowering. The
      ethylene-responsive element-binding factor associated amphiphilic repression
      (EAR) motif was used to construct a CONSTANS-EAR motif repressor gene (CO-Rep),
      which was overexpressed in Arabidopsis under the control of the Cauliflower
      mosaic virus 35S promoter in order to test its potential for flowering time
      regulation under inductive long day conditions. Morphological abnormalities in
      the root and cotyledon formation, and dwarfness were frequently seen in the
      transgenic plants, suggesting that the proper timing, location, and/or level of
      CO-Rep expression are important for its application. In morphologically normal CO
      Rep plants, both bolting and flowering times under inductive long day conditions
      were twofold greater than in controls. As a result of the delay in flowering,
      rosette leaf number at bolting, and rosette and cauline leaf number at flowering
      increased significantly in CO-Rep plants. RT-PCR analysis demonstrated that FT
      expression was greatly reduced in the CO-Rep plants, while endogenous CO and SOC1
      expression levels were not markedly affected. Conservation of CO among a diverse
      range of plant species, and its involvement in a variety of photoperiodic
      responses including flowering, suggests a high potential for use of CO-Rep to
      manipulate such responses in an agronomically desirable manner.

PMID- 17219104
TI  - Plant regeneration from cell suspension-derived protoplasts of Phalaenopsis.
AB  - Protoplasts isolated from cell suspension culture of Phalaenopsis "Wataboushi"
      were cultured by (a) embedding in gellan gum-solidified hormone-free 1/2 New
      Dogashima medium (1/2 NDM) containing 0.44 M sorbitol, 0.06 M sucrose and 0.1 g/l
      L-glutamine (standard method) and (b) beads method using beads of gellan gum or
      sodium alginate as the gelling agents which were surrounded by liquid NDM.
      Although, the two beads methods gave less frequency of initial protoplast
      division than the standard method, the former finally resulted in higher
      frequency of microcolony formation than the latter. The highest frequency of
      microcolony formation (23%) was obtained when protoplasts were embedded in 1% Ca
      alginate beads and subcultured every two weeks by replacing the surrounding
      liquid culture medium with a decrease in sorbitol concentration by 0.1 M.
      Colonies visible to the naked eyes were observed within 2 months of culture and
      the regenerated calluses were transferred onto hormone-free NDM supplemented with
      10 g/l maltose and 0.3% (w/v) gellan gum, on which PLBs were formed and
      proliferated profusely. The PLBs were regenerated into plantlets after changing
      the carbon source to 10 g/l sorbitol and successfully acclimatized to greenhouse
      conditions.

PMID- 17219105
TI  - Enolase autoantibodies and retinal function in multiple sclerosis patients.
AB  - BACKGROUND: Electroretinographic (ERG) abnormalities have been reported in
      multiple sclerosis (MS), as well as the presence of circulating antiretinal
      antibodies. We and others have reported cases of impaired vision and diminished
      ERGs in MS patients with alpha-enolase autoantibodies. Anti-enolase antibodies
      have been implicated in autoimmune retinopathy. We performed this study to
      further explore the relationship between antiretinal antibodies and ERG changes
      in patients with MS. METHODS: Patients with clinically definite MS and normal
      visual acuity were recruited for this study, along with healthy controls. All
      patients and controls had ERG testing done according to ISCEV standards. Patient
      and control sera were analyzed for the presence of antiretinal antibodies using
      Western blot and ELISA techniques, and HLA class II typing was performed using
      polymerase chain reaction. RESULTS: We found a statistically significant
      difference between MS patients and controls in the rod-cone b-wave implicit time
      (p < 0.005). We found autoantibodies against alpha-enolase in 38% of MS patients
      and 11% of controls (p < 0.02). There was no statistically significant difference
      between ERG parameters of MS patients with alpha-enolase autoantibodies compared
      to those without alpha-enolase antibodies. Furthermore, the presence of alpha
      enolase did not associate with a particular HLA haplotype. CONCLUSIONS: Factors
      affecting the retina other than alpha-enolase antibodies may account for the
      delayed rod-cone b-wave implicit times observed in MS patients in this study.
      Anti-enolase antibodies are likely an epiphenomenon of autoimmune disease, and
      are not causing retinopathy in MS patients with normal visual acuity. However,
      the possibility of rare cases of patients with pathogenic alpha-enolase
      autoantibodies can not be excluded. The pathogenic contribution of these
      antibodies in MS patients with visual impairment deserves further investigation.

PMID- 17219106
TI  - Full macular translocation versus photodynamic therapy with verteporfin in the
      treatment of neovascular age-related macular degeneration: 1-year results of a
      prospective, controlled, randomised pilot trial (FMT-PDT).
AB  - BACKGROUND: The purpose of this study was to compare full macular translocation
      (FMT) with photodynamic therapy (PDT) in the treatment of neovascular age-related
      macular degeneration (AMD). METHODS: In a prospective, randomised, non-masked,
      mono-center, pilot-trial, 50 eyes of 50 patients were assigned to either FMT or
      PDT. Baseline and control examinations in 3-monthly intervals over a 12-month
      period included standardized protocol refraction, visual acuity testing and
      fluorescein angiography. Primary outcome measurements were made to establish the
      change in distant visual acuity from the baseline to the 12-month examination.
      The statistical analyses were carried out on the intent-to-treat principle.
      RESULTS: The improvement of one or more ETDRS lines was 56% (14/25) of the eyes
      in the FMT and 16% (4/25) of the eyes in the PDT arm (P = 0.007). Twenty eyes
      (80%) in the FMT and 16 eyes (64%) in the PDT group had less than three ETDRS
      lines of vision loss (P = 0.35). Retinal detachment (six eyes) and diplopia (five
      patients) were recorded in the FMT group. None of the eyes treated in the FMT
      group had phtysis. CONCLUSION: This pilot study showed that no statistically
      significant difference existed between the FMT and PDT in terms of the vision
      loss of less than three ETDRS lines in eyes with neovascular AMD. The chance of
      vision improvement was significantly higher for the patients in the FMT group.
      However, in the era of promising therapy with anti-vascular endothelial growth
      factor for neovascular AMD, FMT should not be offered as a standard primary
      procedure for neovascular AMD.

PMID- 17219107
TI  - The reflection of retinal light response information onto the superior colliculus
      in the rat.
AB  - BACKGROUND: The functional principles of mediation of retina-encoded visual
      information through the optic nerve to the superior colliculus (SC) of the
      contralateral brain hemisphere were investigated in non-drugged and unrestrained
      albino rats by considering the following issues: (1) the type of information
      transmitted, (2) the response components of the retina and SC involved in
      encoding the transmitted information, and (3) the timing of related processes.
      METHODS: The field potential responses for different intensities of flashes,
      under different background illuminations, were simultaneously recorded from the
      sclera area of the eye and the optic layer of the contralateral SC. RESULTS: It
      was found that the b-wave crest of the retinal electroretinogram (ERG) and the
      peak-1 or peak-2 of the SC correlate by their amplitude, while the a-wave trough
      of the retinal ERG and the peak-1 of the SC correlate by their latency. The
      values of these mutually correlating response components were invariably
      determined by the given light response bias of the retina (photoreceptors), the
      change in the photon flux of the light stimulus and, obviously, the change in the
      wavelength of the light stimulus. The a-wave trough, peak-1, b-wave crest and
      peak-2 were invariably induced in this time-order. CONCLUSIONS: The data suggest
      that the information properties of (a) intensity, (b) presentation time and,
      obviously, (c) colour of the light stimulus, such as are shed on the retina, and
      information about the light response bias of the retina are mediated
      correlatively and quantitatively to the cell network system of the SC through the
      optic nerve. These processes must happen during the a-to-b-wave phases of the
      ERG. The data indicate that the random-type variations in the activity of the
      related cellular systems may actually be harnessed in mediating the defined
      information properties of the visual stimulus from the retina to the SC of the
      brain through the optic nerve. This study shows a method of measuring the
      function of the optic nerve.

PMID- 17219108
TI  - Surgical induction of choroidal neovascularization in a porcine model.
AB  - PURPOSE: To develop a reproducible surgical technique for the induction of
      choroidal neovascularization (CNV) in the subretinal space of porcine eyes and to
      analyse the resulting CNV clinically and histologically. METHODS: Two different
      modifications of a surgical technique previously described were compared with the
      original method. In ten porcine eyes retinal pigment epithelial (RPE) cells were
      removed using a silicone tipped cannula, in ten porcine eyes Bruch's membrane was
      perforated once with a retinal perforator without prior RPE removal and in ten
      eyes RPE removal was followed by a single perforation of Bruch's membrane.
      Fifteen of the eyes, five from each group, were enucleated 30 minutes after
      surgery, while the remaining eyes were enucleated after 14 days. Prior to
      enucleation, at day 14, fundus photographs and fluorescein angiograms were
      obtained. Eyes were examined by light microscopy and by immunohistochemical
      staining. In addition to these 30 eyes, two eyes underwent surgery with the
      purpose of subsequent scanning electron microscopic (SEM) examination. RESULTS:
      In eyes enucleated immediately after surgery neuroretinas overlying the induced
      lesions were intact without apparent atrophy of cells regardless of the surgical
      technique applied. The process of RPE removal was found to induce breaks in
      Bruch's membrane and both the size and the number of breaks varied between eyes.
      CNV membranes were identified in 15 of 15 eyes enucleated after 14 days. CNV
      membranes induced by perforation of Bruch's membrane without prior RPE removal
      were significantly thicker than membranes from eyes undergoing both RPE removal
      and Bruch's perforation (p = 0.03) and also thicker than membranes from eyes with
      only RPE-removal (p < 0.01). CNV membranes from eyes with perforation of Bruch's
      membrane without prior RPE removal had a higher cellular content and were more
      richly vascularized and also exhibited the highest propensity to leak in
      fluorescense angiograms. CONCLUSION: All three surgical techniques were capable
      of inducing CNV, but the one applying perforation of Bruch's membrane without RPE
      removal was easier to reproduce and involved fewer variables than the techniques
      utilizing RPE removal. The presence of RPE cells seems to affect both the
      morphology and cellular composition of induced CNV.

PMID- 17219110
TI  - A novel oculoplastic surgery for exposed glaucoma drainage shunt by using
      autologous graft.

PMID- 17219109
TI  - Muller cells as players in retinal degeneration and edema.
AB  - BACKGROUND: Under normal conditions, Muller cells support neuronal activity and
      the integrity of the blood-retinal barrier, whereas gliotic alterations of Muller
      cells under pathological conditions may contribute to retinal degeneration and
      edema formation. A major function of Muller cells is the fluid absorption from
      the retinal tissue, which is mediated by transcellular water transport coupled to
      currents through potassium channels. METHODS: Alterations of retinal Muller cells
      under pathological conditions were investigated by immunohistochemistry and
      recording their behavior under osmotic stress. RESULTS: In animal models of
      various retinopathies, e.g., retinal ischemia, ocular inflammation, retinal
      detachment, and diabetes, it was found that Muller cells decrease the expression
      of their major potassium channel (Kir4.1). This alteration is associated with an
      impairment of the rapid water transport across Muller cell membranes, as
      recognizable in the induction of cellular swelling under hypoosmolar conditions.
      Osmotic swelling of Muller cells is also induced by oxidative stress and by
      inflammatory mediators such as arachidonic acid and prostaglandins. CONCLUSIONS:
      The data suggest that a disturbed fluid transport through Muller cells is (in
      addition to vascular leakage) a pathogenic factor contributing to the development
      of retinal edema. Pharmacological re-activation of the retinal water clearance by
      Muller cells may represent an approach to the development of new edema-resolving
      drugs. Triamcinolone acetonide, which is clinically used to resolve edema,
      prevents osmotic swelling of Muller cells as it induces the release of endogenous
      adenosine and subsequent A1 receptor activation which results in the opening of
      ion channels. Apparently, triamcinolone resolves edema by both inhibition of
      vascular leakage and stimulation of retinal fluid clearance by Muller cells.

PMID- 17219111
TI  - Investigation of thermal effects of infrared lasers on the rabbit retina: a study
      in the course of development of an active subretinal prosthesis.
AB  - BACKGROUND: Retinal implants are intended to replace photoreceptors in patients
      suffering from degenerative retinal diseases such as retinitis pigmentosa. Data
      show that photodiodes in subretinal implants are not powerful enough to stimulate
      overlying retinal tissue by simply transforming light energy into electrical
      energy. Therefore, infrared (IR) irradiation has been envisioned to supply
      additional energy. While epiretinal implants mostly use induction coils for
      wireless energy transfer, IR irradiation seems to be an additional option. This
      study investigated the feasibility of an IR energy supply for an active
      subretinal implant by assessing thermal effects of IR irradiation onto the rabbit
      retina. METHODS: Polyimide foil strips carrying an optical sensor as well as a
      thermal sensor were implanted into the subretinal space of the eyes of nine
      rabbits using a transchoroidal surgical approach. The area of the thermal sensor
      was irradiated by an IR laser (830 nm) focused on the device. The sensor provided
      simultaneous real-time measurements of absolute temperature and irradiation
      density, allowing direct correlation of the temperature increase to different
      intensities of IR irradiation. Possible IR-related damage to the retina was
      examined in histological sections. Temperature changes in living and dead animals
      were evaluated as a function of IR irradiation power of between 0.1 mW and 40 mW
      (0.03 mW/mm2-12.7 mW/mm2). RESULTS: We found an exponential relationship between
      IR irradiation power and temperature increase over the whole range (up to 12.7
      mW/mm2) in the living animal. The maximum temperature increase caused by IR
      irradiation of 40 mW (12.7 mW/mm2) was 4.5 degrees C. The ratio of temperature
      increase to IR irradiation density postmortem (i.e., without ocular blood flow)
      was linear over the whole range, with 1.15 degrees C per 1 mW/mm2. Thus, the
      cooling effect of ocular blood flow varied depending on IR irradiance density. In
      histological sections, no IR-induced damage to the retina was detected.
      CONCLUSIONS: A temperature increase of 3.2 degrees C in the living rabbit eye is
      to be expected when powering a subretinal implant with 15 mW (4.8 mW/mm2) IR
      power, the wattage used in an external power supply for an active implant with
      1,500 electrodes. This appears to be a tolerable increase for ocular tissue.

PMID- 17219112
TI  - Weak transient response of chronic uveitic macular edema to intravitreal
      bevacizumab (Avastin).

PMID- 17219113
TI  - Indocyanine green angiographic findings of Dalen-Fuchs nodules in Vogt-Koyanagi
      Harada disease.
AB  - PURPOSE: The purpose of this study was to analyze indocyanine green (ICG)
      angiographic findings of Dalen-Fuchs nodules in Vogt-Koyanagi-Harada (VKH)
      disease. METHODS: ICG angiograms of 15 patients (30 eyes) with Dalen-Fuchs
      nodules in VKH disease of between 2 months and 5 years after the initial
      diagnosis were retrospectively studied. Findings of ICG angiography were compared
      with features of fundus fluorescein angiography (FFA). RESULTS: Dalen-Fuchs
      nodules were easily found in the inferior (30 eyes, 100%) and temporal periphery
      (22 eyes, 73%) and showed two kinds of fluorescence in ICG angiography. In ten
      patients (20 eyes), the nodules showed small round hypofluorescent dark dots in
      the whole process of angiography, and the dark dots were larger in size than the
      nodules in FFA. Disease course in these patients was relatively long-between 1
      year and 5 years. On clinical examination, the nodules were atrophic, and
      hyperpigmentation was found around them. In another five patients (ten eyes),
      parts of the nodules showed small hyperfluorescent dots in the early phase, but
      they were faint in the intermediate phase and became large, hypofluorescent dark
      dots in the late phase. Disease course in these patients was between 2 and 8
      months. The nodules were bright yellow, fresh, and much larger than those in the
      first kind of ICG fluorescence. CONCLUSIONS: Dalen-Fuchs nodules in VKH are
      mostly present in the inferior and temporal periphery. The two kinds of
      fluorescence of Dalen-Fuchs in ICG angiography may reflect obliteration of
      choriocapillaris under the nodules and different quantities of lipofuscin in the
      nodules at different time points of the disease.

PMID- 17219114
TI  - Successful treatment of a large choroidal abscess in an immunocompetent child.
      Treatment of a choroidal abscess.
AB  - BACKGROUND: We report the case of a systemically well 4-year-old Aboriginal boy
      who developed a choroidal abscess after being poked in the left eye with a blunt
      object. CASE REPORT: This boy presented with redness and reduced vision in the
      left eye after a blunt object was poked into his eye by his sibling. He was noted
      to have a choroidal mass which finally manifested as a choroidal abscess.
      RESULTS: His initial visual acuity was 6/60, and dilated fundus examination
      demonstrated a localised solid-appearing choroidal elevation involving the
      posterior pole, including the macula. An ultrasound of the eye revealed a
      choroidal haematoma with an atypical appearance, whose height was 8 mm with a
      base of 12 mm x 10 mm. The lesion failed to resolve, and eventually resulted in
      orbital cellulitis that did not respond to intravenous and topical antibiotic
      treatment. He then went on to achieve complete visual recovery after successful
      management by transcleral incision, drainage and systemic antibiotic therapy.
      CONCLUSION: Choroidal abscess has been described in patients who are debilitated,
      immunocompromised or suffer with systemic disease such as cystic fibrosis or
      endocarditis. This case represents a unique report of staphylococcal choroidal
      abscess in a healthy child that completely resolved after transcleral drainage
      and systemic antibiotics.

PMID- 17219115
TI  - Horseshoe-like macular tear following recurrent branch retinal vein occlusion.
AB  - BACKGROUND: A macular hole can develop as a late complication secondary to a
      branch retinal vein occlusion (BRVO). We report about an atypical horseshoe-like
      tear occurring in the fovea after recurrent BRVO. METHODS: An interventional case
      report. RESULTS: In 1997, a 53-year-old man was seen with an occlusion of macular
      part of inferior temporal vein of the retina on the left eye. After experiencing
      several recurrent BRVO in this eye, 6 years later he presented with a horseshoe
      like tear in the fovea. Visual acuity was 20/200. The patient underwent standard
      three-port vitrectomy and installation of C3F8 16%. Intraoperatively, massive
      traction of the vitreous was detected on the edges of the tear. Six months after
      the operation, the tear remained attached. The visual acuity was 20/200.
      CONCLUSIONS: The uniqueness of the presented case is the occurrence of a macular
      tear following recurrent BRVO, its horseshoe-like shape and foveal location. To
      the best of our knowledge, this is the first report on a horseshoe-like tear seen
      in the fovea secondary to BRVO. We assume that chronic macular edema and retinal
      ischemia following BRVO were additional factors beside the vitreous traction,
      contributing to the formation of the macular tear. Anatomical closure of the tear
      and stabilisation of visual acuity can be achieved by vitreoretinal surgery.

PMID- 17219116
TI  - Quantification of metamorphopsia in patients with epiretinal membranes before and
      after surgery.
AB  - BACKGROUND: To evaluate quantification of metamorphopsia before and after the
      removal of unilateral epiretinal membrane (ERM). METHODS: One hundred and four
      consecutive patients with unilateral ERM scheduled for membrane peeling were
      prospectively enrolled. A complete ophthalmologic examination was performed.
      Metamorphopsia was evaluated, with standard Amsler grids and a laser grid
      generated with a scanning laser ophthalmoscope (SLO). The SLO procedure
      determined the area of distortion and was performed twice at a 30-minute interval
      to evaluate its reproducibility. The result was considered to be reliable when
      the area of distortion was identical in both SLO test sessions. One year after
      surgery, a complete ophthalmologic examination was performed. Metamorphopsia was
      again quantified with the SLO procedure. RESULTS: Before surgery, a reliable
      quantification of metamorphopsia (defined as area of distortion) could be
      performed in 98 patients (94%). Among these patients, 85 completed the follow-up
      of 12 months after surgery. Of these 85 patients, visual distortions had been
      detected preoperatively in 48 patients (56%). One year after surgery, visual
      distortions were detected in only 11 patients (13%). In 48 patients with
      preoperative distortions, the decrease of the area of distortion correlated with
      the change in visual acuity (r = -0.460, p = 0.011). CONCLUSIONS: SLO-based
      evaluation of metamorphopsia made it possible to provide a fast and reliable
      method for preoperative and post-operative quantification of visual distortion in
      patients undergoing ERM removal.

PMID- 17219117
TI  - Treatment of exposed explants with donor sclera and amniotic membrane.

PMID- 17219118
TI  - Treatment of central retinal vein occlusion by radial optic neurotomy in 107
      cases.
AB  - BACKGROUND: To evaluate the potential role of radial optic neurotomy (RON), a new
      surgical technique has been recently proposed for treating central retinal vein
      occlusion (CRVO). It is hypothesized that CRVO constitutes a neurovascular
      compartment syndrome at the site of the lamina cribrosa, which can be alleviated
      by performing a radial incision at the nasal part of the optic nerve head,
      relaxing the cribriform plate and the adjacent sclera. METHODS: One hundred and
      seven patients were treated with RON for CRVO at five collaborating
      ophthalmologic centers. All patients were evaluated by a standardized protocol.
      For analysis of the angiographic and fundus findings, reference images were used.
      Intraoperative and postoperative complications were reviewed. RESULTS: On 55
      right and 52 left eyes of 107 patients (55.6% male, 44.4% female) with a median
      age of 68 years (range 21-91 years), RON was performed. The median follow-up time
      was 6 months (range 1-24 months). The median preoperative visual acuity (VA) was
      0.05 (logMAR 1.3), increasing to a median postoperative VA of 0.08 (logMAR 1.1).
      Patients with an interval of more than 90 days between RON and onset of CRVO
      showed no significant change in VA at the 6-month follow-up. Severe peripapillary
      swelling of the optic nerve head prior to RON resulted in an average increase of
      4.2 lines in VA at the 6-month follow-up. Angiographic findings of shunt vessels
      were seen in 18/30 cases after 12 months and were accompanied by an average
      improvement of VA of six lines. Visual field tests showed various defects in
      86.8% of all cases. In one patient an iatrogenic injury of the central retinal
      artery occurred (0.9%). CONCLUSION: Despite the potential risk of visual field
      defects, RON seems to be a quite safe procedure. The majority of patients showed
      rapid normalization of the morphologic fundus findings, with an improvement in VA
      uncommon for the natural history of CRVO. No significant change in VA was seen in
      patients with an interval of more than 90 days between the onset of CRVO and RON.
      A prospective study is warranted for further investigation.

PMID- 17219120
TI  - 18-FDG PET/CT staging of ocular sebaceous cell carcinoma.

PMID- 17219119
TI  - Structural alterations of the erythrocyte membrane proteins in diabetic
      retinopathy.
AB  - BACKGROUND: Several rheological disorders of the erythrocytes, such as increased
      aggregation and decreased deformability, have been observed in diabetes mellitus
      and have been implicated in the development of diabetic microangiopathy.
      Structural alterations of the erythrocyte membrane proteins caused by the
      diabetic process may be at the origin of those observations. In the present
      study, we searched for erythrocyte membrane protein alterations in diabetic
      retinopathy. METHODS: We examined peripheral blood samples from 40 type-2
      diabetic patients with diabetic retinopathy of variable severity (19 males and 21
      females, mean age 66.8 years, Group A) and we compared them with samples from 19
      type-2 diabetic patients without diabetic retinopathy (13 males and six females,
      mean age 66.5 years, Group B) and 16 healthy volunteers (eight males and eight
      females, mean age 65.6 years, Group C). Erythrocyte membrane ghosts from all
      samples were subjected to SDS-PAGE, and the electrophoretic pattern of
      transmembrane and cytoskeletal proteins was analysed for each sample. The protein
      quantification of each electrophoretic band was accomplished through scanning
      densitometry. RESULTS: No significant deviations from normal electrophoresis were
      observed in Groups B and C, apart from an increase in band 8 in two samples from
      Group B (11%). In contrast, in 14 samples from Group A (35%) we detected
      increases in protein band 8 and/or membrane-bound haemoglobin along with a
      decrease in spectrin. Moreover, increased mobility of band 3, an aberrant high
      molecular weight (MW) (> 255 kDa) band and a low MW (42 kDa) band were evident in
      ten samples from Group A (25%). Glycophorins were altered in 46% of Group-A
      patients versus 38% of Group-B patients. Females and patients with long duration
      of diabetes presented more electrophoretic abnormalities. CONCLUSIONS: Structural
      alterations of the erythrocyte membrane proteins are shown for the first time in
      association with diabetic retinopathy. Their detection may serve as a blood
      marker for the development of diabetic microangiopathy. Further studies are
      needed to assess whether pharmaceutical intervention to the rheology of
      erythrocytes can prevent or alleviate microvascular diabetic complications.

PMID- 17219121
TI  - High-density silicone oil (Densiron) as a primary intraocular tamponade: 12-month
      follow up.
AB  - BACKGROUND: The high-density silicone oil (Densiron 68), a mixture of F6H8 with
      silicone oil, seems to be a therapeutic option, at least in selected patients
      with complex inferior retinal re-detachment, where standard procedures have
      already failed. In an interventional case series we used Densiron as a primary
      endotamponade. METHODS: Twelve eyes of 12 patients aged 31 years to 85 years with
      inferior complex rhegmatogenous retinal detachment with secondary proliferative
      vitreoretinopathy (PVR) grades CP2 to CA8 were included. Surgical techniques
      (pars plana vitrectomy, membrane peeling, retinotomy, retinectomy,
      endophotocoagulation, cryocoagulation, endotamponade) did not include a scleral
      buckling procedure (except one eye). Mean duration of the Densiron endotamponade
      was 78.3 +/- 29.74 days, with a mean follow up after removal of 400.6 +/- 85.4
      days. RESULTS: After Densiron removal, four patients (33.3%) showed a stable
      reattached retina without further interventions, while, in six patients (50%),
      recurrent retinal re-detachment appeared during endotamponade, generally within 2
      months. One patient (8.3%) developed re-detachment 5 months after Densiron
      removal. One eye (8.3%) lost light perception due to severe intraretinal fibrosis
      with chronic hypotonia, despite complete retinal re-attachment. Visual acuity
      improved from mean logarithm of the minimum angle of resolution (logMAR) of 2.95
      +/- 1.21 to 1.87 +/- 1.32 (statistically significant, P = 0.022). Side effects
      included temporary inflammatory reaction/fibrin accumulation (n = 2/2), moderate
      to-severe intraretinal fibrosis (n = 3), elevated intraocular pressure (IOP) (n =
      3), emulsification (n = 2), sterile hypopyon (n = 1), vitreous haemorrhage (n =
      1) and chronic hypotony (n = 1). CONCLUSION: Primary anatomical success rate of
      33.3% was less encouraging than as expected. Especially, re-detachments within
      the posterior staphyloma in highly myopic patients were common during Densiron
      endotamponade. However, the surgical success increased to 75% after
      reintervention, even without the use of an additional encircling band. The
      observed adverse effects and the functional outcomes do not contraindicate the
      use of Densiron as an internal tamponade for a period of 3 months.

PMID- 17219122
TI  - The tale and molecular trail of a disseminated ocular adnexal malt lymphoma.
AB  - PURPOSE: To report a case of a MALT lymphoma of the eyelid, which recurred in
      several sites over a time period of 14 years, and where the identical B-cell
      clone could be demonstrated in most samples using polymerase chain reaction (PCR)
      and GeneScan analysis. METHODS: Clinical, histologic, immunohistochemical, PCR
      and GeneScan analysis findings are presented. RESULTS: A 58-year-old woman
      presented with a swelling of the left lower lid. Excisional biopsy of the tumour
      revealed a low-grade malignant B-cell Non-Hodgkin lymphoma (NHL) of MALT type.
      Despite localized radiochemotherapy, the patient developed recurrences occurring
      in the pharynx, in the right orbit, in the skin of the right foot, and in the
      bone marrow 1, 7, 11 and 14 years, respectively, after establishment of the first
      diagnosis. PCR for a rearrangement of the immunoglobulin heavy chains (IgH) and
      GeneScan analysis of the samples produced amplificates identical in size at most
      sites, indicating derivation from the same B-cell clone. CONCLUSIONS: It is
      generally assumed that ocular adnexal MALT lymphoma is associated with an
      indolent clinical course. Using IgH-PCR and GeneScan analysis, we demonstrate
      that the current case illustrates that these lymphomas do indeed require regular
      control examinations following treatment, as they often recur and disseminate in
      some patients in an unpredictable manner.

PMID- 17219123
TI  - Optic disc edema in non-arteritic anterior ischemic optic neuropathy.
AB  - We investigated the clinical characteristics, time to resolution and the factors
      that influence it, and evolutionary pattern of optic disc edema (ODE) in non
      arteritic anterior ischemic optic neuropathy (NA-AION). Our study was conducted
      in 591 consecutive patients (749 eyes) with NA-AION who fulfilled our inclusion
      criteria. On their first visit to our clinic, all patients had a detailed
      ophthalmic and medical history, a comprehensive ophthalmic evaluation, and
      stereoscopic color fundus photography and fluorescein fundus angiography. On each
      follow-up visit, the same ophthalmic evaluation was performed, except for
      fluorescein fundus angiography. The effect of steroid therapy on ODE was
      evaluated in a "patient choice study" in 723 eyes, i.e., patients who voluntarily
      opted to have (343 eyes) or not have (380 eyes) this therapy. To identify the
      factors that influence time to ODE resolution, parametric regression models for
      interval-censored data were fitted by maximum likelihood estimation using an SAS
      procedure. Our results indicate that the overall median time (25-75th percentile)
      to spontaneous resolution of ODE from the onset of visual loss was 7.9 (5.8-11.4)
      weeks. The ODE resolution time was longer in diabetics than in non-diabetics (p =
      0.003) in the single factor model. Multi-factor analysis showed that worse
      initial visual field defects (p < 0.0001) and worse visual acuity (p = 0.04) were
      associated with a faster resolution of ODE. Those treated with steroid therapy
      within 2 weeks after onset of NA-AION had significantly (p = 0.0006) faster ODE
      resolution than untreated cases. Severity of initial visual loss and systemic
      diseases were identical in steroid treated and untreated patients. A
      characteristic evolutionary pattern of ODE in NA-AION was observed. In
      conclusion, our study showed that in NA-AION the time course for resolution of
      ODE is shorter with greater severity of initial visual field and visual acuity
      loss, which may relate to the number of axons permanently damaged during the
      acute stage. Steroid therapy was associated with shorter time to resolution of
      ODE. Resolution of ODE goes through a characteristic evolutionary process.

PMID- 17219124
TI  - Rate of epithelialisation and re-operations in corneal ulcers treated with
      amniotic membrane transplantation combined with botulinum toxin-induced ptosis.
AB  - OBJECTIVE: To examine the efficacy of amniotic membrane transplantation (AMT)
      and/or botulinum toxin type A-induced ptosis (Dysport) in the treatment of
      corneal ulcerations of different entities. METHODS: Retrospective evaluation of
      137 cases of corneal ulcers which have been treated with AMT, botulinum toxin
      type A and perforating keratoplasty (pKP). Regarding corneal ulcerations the
      patients were divided into three groups: group A, patients initially having
      received an AMT (92 eyes eventually followed by AMT or pKP as a second
      intervention); group B, patients initially having received an AMT (32 eyes
      followed by botulinum toxin type A injection in the upper lid as a second
      intervention); group C, patients initially treated only by botulinum toxin type A
      injection (13 eyes followed occasionally by AMT or pKP or additional botulinum
      toxin type A injection). Additionally, we analysed the complete epithelialisation
      rate of the ocular surface in respect to different ocular and systemic diseases
      and compared the frequency of re-operations in each group. RESULTS: The overall
      follow-up was 14.2 (+/-14.7 months; range from 1 to 60 months). The total
      frequency of re-operations was 45.3% (overall time until complete
      epithelialisation 12.7 (+/-6.1) days). If the patient was initially treated with
      an AMT (group A), the re-operation rate was 44.6%. Treating affected eyes in this
      group with a subsequent amniotic membrane resulted in a reduction of re-operation
      rate to 30.4%. In cases with induced ptosis by injecting botulinum toxin type A
      in the M. levator palpebrae (group B), the re-operation frequency could be
      reduced to 34.4% with similar times of epithelialisation [group A: 12.0 (+/-6.5)
      days and group B: 11.7 (+/-5.5) days]. In group C, with botulinum toxin type A
      alone initially, the re-operation rate of 69.2% was the highest one compared with
      groups A and B; this rate could be drastically reduced by a following AMT to
      23.1%. Surprisingly, in the few successful cases with botulinum toxin type A
      alone a quite low epithelialisation time of 6.5 (+/-1.3) days was achieved, but
      turned out to be similar after additional interventions if compared with the
      other groups (botulinum toxin type A + AMT: 15.7 (+/-4.9) day). CONCLUSION: AMT
      alone and combined with botulinum toxin type A-induced ptosis is an effective
      surgical approach for managing severe corneal ulcerations by promoting wound
      healing and stabilizing ocular surface homeostasis.

PMID- 17219125
TI  - The Freiburg Visual Acuity Test-variability unchanged by post-hoc re-analysis.
AB  - BACKGROUND: The Freiburg Visual Acuity and Contrast Test (FrACT) has been further
      developed; it is now available for Macintosh and Windows free of charge at
      http://www.michaelbach.de/fract.html . The present study sought to reduce the
      test-retest variability of visual acuity on short runs (18 trials) by post-hoc re
      analysis. METHODS: The FrACT employs advanced computer graphics to present
      Landolt Cs over the full range of visual acuity. The sequence of optotypes
      presented follows an adaptive staircase procedure, the Best-PEST algorithm. The
      Best-PEST threshold obtained after 18 trials was compared to the result of a post
      hoc re-analysis of the acquired data, where both threshold and slope of the
      psychometric function were estimated via a maximum-likelihood fit. RESULTS:
      Testing time was 1.7 min per run on average. Test-retest reproducibility was +/-2
      lines (or +/-0.2 logMAR) for a 95% confidence band (using 18 optotype
      presentations per test run). Post-hoc psychometric fitting reproduced the Best
      PEST result within 1%, although the individual slopes varied widely; test-retest
      reproducibility was not improved. CONCLUSIONS: The FrACT offers advantages over
      traditional chart testing with respect to objectivity and reliability. The
      similarity between the results of the Best-PEST vs. post-hoc analysis, fitting
      both slope and threshold, suggest that there is no disadvantage to the constant
      slope assumed by Best PEST. Furthermore, since variability was not reduced by
      post-hoc analysis, for high reliability more trials should be employed than the
      18 trials per run used here.

PMID- 17219126
TI  - Cyclodialysis ab interno as a surgical approach to intractable glaucoma.
AB  - PURPOSE: In glaucoma filtration surgery, the problem of subconjunctival scarring
      has still not been satisfactorily solved. Suprachoroidal drainage of aqueous
      humour offers a promising, alternative option for intractable glaucoma. We here
      present a clinical study on the surgical approach of gonioscopic cyclodialysis ab
      interno. PATIENTS AND METHODS: Twenty-eight eyes of 20 patients with intractable
      glaucoma were included in this prospective, consecutive, case-control study. The
      eyes had had a mean of 4.4 +/- 2.4 previous antiglaucomatous interventions.
      Baseline intraocular pressure (IOP) was 34.3 +/- 10.5 mmHg despite maximum
      therapy. Under gonioscopic control, cyclodialysis ab interno was performed over
      two clock times to gain access to the suprachoroidal space. No additional
      trabecular meshwork surgery was performed. Success was defined as a lowering of
      IOP to below 21 mmHg without the need for further medication or intervention.
      RESULTS: Mean postoperative IOP was 14.6 +/- 12.4 mmHg. Mean follow-up (FU) for
      all eyes was 121.8 days. After a mean of 60 days, 21 eyes (75%) needed further
      surgical intervention. Qualified success was seen in four eyes (14.3%), with a
      mean FU of 383.6 days. Three eyes (10.7%) showed absolute success after a mean FU
      period of 202.7 days. In our series, we obtained the best results for phakic
      eyes, followed by pseudophakic and aphakic eyes. CONCLUSION: The results of this
      study do not provide convincing evidence of the functional efficacy of
      cyclodialysis ab interno. Nevertheless, the technique is easy to perform and
      offers safe and atraumatic access to the resorptive capability of the choroid.
      Conjunctival manipulation is avoided. Contrary to reports in the current
      literature, in our series, the best results were obtained for phakic eyes, though
      the small number of eyes included does not allow reliable statistics. Further
      studies will need to focus on the use of different space-retaining substances or
      a widening of the cyclodialysis cleft to improve surgical outcome.

PMID- 17219127
TI  - Primary cutaneous anaplastic large cell lymphoma in a young child.

PMID- 17219128
TI  - PHACES syndrome with small, late-onset hemangiomas.
AB  - Although hemangiomas are the hallmark of the PHACES syndrome, they may be
      nonexistent at birth and may not develop until later in early infancy. We report
      an infant who presented initially with cardiac defect, sternal nonunion,
      supraumbilical raphe, and congenital hypothyroidism without any hemangioma, and
      who subsequently developed facial hemangiomas at 2 months of age. We noted that
      there is a possibility that hemangiomas may subsequently develop later in early
      infancy and congenital hypothyroidism may be associated with the PHACES syndrome.

PMID- 17219129
TI  - Paediatric multiple sclerosis and acute disseminated encephalomyelitis in
      Germany: results of a nationwide survey.
AB  - The aim of this study was to evaluate the incidence of paediatric multiple
      sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) in Germany. In a
      prospective nationwide survey carried out between 1997 and 1999, all registered
      new cases of paediatric MS and ADEM with an onset before the age of 16 years were
      evaluated using a standardised questionnaire. A total of 132 patients with
      suspected or definite MS and 28 patients with an assumed diagnosis of ADEM were
      reported. Among these, 82% of the MS patients were 10 years of age or older, as
      opposed to 18% in the ADEM-cohort. The female-to-male ratio was 1.2:1 in the MS
      cohort and 0.8:1 in the ADEM-cohort. Manifestation was polysymptomatic in 67% of
      the MS patients compared to 86% of the ADEM patients. The most frequent primary
      symptoms in the MS-cohort were cerebellar (44%), sensory (39%) or visual (36%),
      followed by brainstem (30%), pyramidal (29%) and cerebromental (22%) complaints.
      CONCLUSION: The incidence of paediatric MS in Germany is more than fourfold
      higher than that of paediatric ADEM; in addition, it shows a strikingly different
      age-distribution. With an estimated minimum of 50 new cases per year, the
      incidence of paediatric MS in Germany is much more frequent than previously
      believed.

PMID- 17219130
TI  - Behavioural versus physiological mediation of life history under predation risk.
AB  - Predator-generated variation in prey energy intake remains the dominant
      explanation of adaptive response to predation risk in prey life history,
      morphology and physiology across a wide range of taxa. This "behavioural
      hypothesis" suggest that chemical or visual signals of predation risk reduce prey
      energy intake leading to a life history characterized by a small size and late
      age at maturity. However, size-selective predation can induce either smaller size
      early age or large size-late age life history. The alternative "physiological
      hypothesis" suggests that size-selective cues decouple the relationship between
      energy and life history, acting instead directly on development. Here we use a
      series of experiments in a fish-daphnid predator-prey system to ask whether size
      selective predator cues induce a physiological mediation of development,
      overshadowing behaviourally based changes in food intake. We found fish chemical
      cues reduce the net energy intake in Daphnia magna, suggesting a behaviourally
      mediated reduction in energy. Experimental manipulation of food levels show
      further that reductions in food lead to later but smaller size at maturity.
      However, in line with the physiological hypothesis, we show that D. magna matures
      earlier and at a smaller size when exposed to fish predation cues. Furthermore,
      our data shows that they do this by increasing their development rate (earlier
      maturity) for a given growth rate, resulting in a smaller size at maturity. Our
      data, from a classic size-selective predation system, indicate that predator
      induced changes in this system are driven by physiological mediation of
      development rather than behavioural mediation of energy intake.

PMID- 17219131
TI  - Ecosystem controls on nitrogen fixation in boreal feather moss communities.
AB  - N fixation in feather moss carpets is maximized in late secondary successional
      boreal forests; however, there is limited understanding of the ecosystem factors
      that drive cyanobacterial N fixation in feather mosses with successional stage.
      We conducted a reciprocal transplant experiment to assess factors in both early
      and late succession that control N fixation in feather moss carpets dominated by
      Pleurozium schreberi. In 2003, intact microplots of moss carpets (30 cm x 30 cm x
      10-20 cm deep) were excavated from three early secondary successional (41-101
      years since last fire) forest sites and either replanted within the same stand or
      transplanted into one of three late successional (241-356 years since last fire)
      forest sites and the transverse was done for late successional layers of moss.
      Moss plots were monitored for changes in N-fixation rates by acetylene reduction
      (June 2003-September 2005) and changes in the presence of cyanobacteria on moss
      shoots by microscopy (2004). Forest nutrient status was measured using ionic
      resin capsules buried in the humus layer. Late successional forests exhibit high
      rates of N fixation and consistently high numbers of cyanobacteria on moss
      shoots, but low levels of available N. Conversely, early successional forests
      have higher N availability and have low rates of N fixation and limited presence
      of cyanobacteria on moss shoots. Transplantation of moss carpets resulted in a
      significant shift in presence and activity of cyanobacteria 1 year after
      initiation of the experiment responding to N fertility differences in early
      versus late successional forests.

PMID- 17219132
TI  - Brain reserve capacity in frontotemporal dementia: a voxel-based 18F-FDG PET
      study.
AB  - PURPOSE: The association of the regional cerebral metabolic rate of glucose
      utilisation (rCMRglc) and years of schooling has been extensively studied in
      Alzheimer's disease (AD). The results suggest that brain reserve capacity (BRC)
      allows patients with more years of schooling to cope better with AD pathology.
      The objective of this study was to provide initial evidence for BRC in
      frontotemporal dementia (FTD). METHODS: Twenty-nine patients with FTD and 16
      healthy age- and education-matched controls underwent PET imaging of the brain
      with 18F-fluoro-2-deoxy-glucose. A group comparison of rCMRglc was conducted
      between patients and controls and the output was saved as region of interest
      (ROI). A linear regression analysis with education as the independent and rCMRglc
      as the dependent variable, adjusted for age, gender and total score on the CERAD
      neuropsychological battery, was conducted in SPM2 over the pre-assigned ROI.
      RESULTS: Patients showed a reduced rCMRglc in almost the entire prefrontal cortex
      and the anterior cingulate cortex as compared with controls (p < 0.05 corrected
      for multiple comparisons). The regression analysis revealed a significant
      negative association between years of schooling and rCMRglc in the bilateral
      inferior frontal cortex (p < 0.001, uncorrected for multiple comparisons), which
      was independent of demographic variables and cognitive performance level. There
      was a strong negative correlation of rCMRglc and education (r = -0.45).
      CONCLUSION: The study provides initial evidence for BRC in FTD. The findings
      suggest that interindividual differences in educational level affect BRC by
      partially mediating the relationship between neurodegeneration and the clinical
      manifestation of FTD.

PMID- 17219133
TI  - Normal limits of ejection fraction and volumes determined by gated SPECT in
      clinically normal patients without cardiac events: a study based on the J-ACCESS
      database.
AB  - PURPOSE: Quantitative gated single-photon emission computed tomography (SPECT) is
      known to have high accuracy and precision for measurement of the principal
      cardiac functional parameters. We hypothesised that normal values for EF and LV
      volumes may differ among nationalities, and that optimal threshold values
      specific to the study population are required. METHODS: Among 4,670 consecutively
      registered patients for a J-ACCESS (Japanese investigation regarding prognosis
      based on gated SPECT) study from 117 hospitals, a total of 268 (149 women, 119
      men) were selected who had no baseline cardiac diseases and had experienced no
      cardiac events during the preceding 3-year period. A gated SPECT study was
      performed with 99mTc-tetrofosmin and analysed with Cedars Sinai Medical Center's
      quantitative gated SPECT (QGS) software. The results in respect of ejection
      fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV) and stroke
      volume (SV), and EDV, ESV and SV normalised by body surface area (EDVI, ESVI and
      SVI), were calculated and summarised to obtain normal limits. RESULTS: EF for
      women and men was 74 +/- 9% and 63 +/- 7%, respectively (p < 0.0001). EDV, ESV
      and SV were significantly smaller in women than in men. Based on multiple
      regressions for linear models, the primary and secondary predictors of EF, EDVI,
      ESVI were gender and age. By stepwise multiple regression analysis, a
      statistically significant third predictor for EDV, ESV, SV and SVI was body
      weight. No colinearity was found between age and body weight. Important factors
      for the studied Japanese population included a high incidence of small hearts in
      women and the relatively advanced age of the population (the mean age +/-SD was
      64.1 +/- 10.0 years for women and 60.9 +/- 11.7 years for men). CONCLUSION: EF
      and volumes determined by gated SPECT with QGS were significantly affected by
      gender and age, with body weight as a third predictor for volumes. Moreover, the
      normal limits were so specific for the population studied that standards
      appropriate for the study in question should be utilised.

PMID- 17219134
TI  - Assessment of quantitative FDG PET data in primary colorectal tumours: which
      parameters are important with respect to tumour detection?
AB  - PURPOSE: The impact of quantitative parameters on the differentiation of primary
      colorectal tumours from normal colon tissue was assessed. Dynamic PET data (DPET)
      were acquired, and compartment and non-compartment modelling applied. The
      discriminant power of single parameters and the combination of PET parameters was
      assessed. All lesions were confirmed by histology. METHODS: FDG DPET studies were
      acquired in 22 patients with colorectal tumours prior to surgery. Five of these
      patients also had liver metastases at the time of the PET study. The SUV 56-60
      min p.i. was included in the evaluation. A two-tissue compartment model was
      applied and the parameters k1-k4 as well as the fractional blood volume (VB) were
      obtained. The FDG influx was calculated from the compartment data. Non
      compartment modelling was used to calculate the fractal dimension (FD) of the
      time-activity data. RESULTS: FD, SUV, influx and k3 were the most important
      single parameters for lesion differentiation. The highest accuracy was achieved
      for FD (88.78%). The overall tracer uptake was mainly dependent on k3 and not on
      k1 or VB. The support vector machines (SVM) algorithm was used to predict the
      classification based on the combination of individual PET parameters. The overall
      accuracy was 97.3%, with only one false positive case and no false negative
      results. The analysis of the subgroup of five patients with primary tumours and
      synchronous metastases revealed no significant differences for the individual PET
      parameters. However, VB tended to be lower while k1 and k2 were higher in
      patients with synchronous metastases. The SVM classification analysis predicted
      the presence of metastases based on the PET data of the primary tumour in three
      of five patients. CONCLUSION: Quantitative FDG PET studies provide very accurate
      data for the differentiation of primary colorectal tumours from normal tissue.
      The use of quantitative data has the advantage that the detection of a colorectal
      tumour is not primarily dependent on the individual assessment and experience of
      the physician evaluating the FDG PET data only visually. The results suggest that
      the presence of metastatic lesions may be predicted by analysis of the dynamic
      PET data of the corresponding primary tumour. Further studies are needed to
      assess this aspect in detail.

PMID- 17219135
TI  - Molecular imaging of vascular cell adhesion molecule-1 expression in experimental
      atherosclerotic plaques with radiolabelled B2702-p.
AB  - PURPOSE: VCAM-1 plays a major role in the chronic inflammatory processes present
      in vulnerable atherosclerotic plaques. The residues 75-84 (B2702-p) and 84-75/75
      84 (B2702-rp) of the major histocompatibility complex-1 (MHC-1) molecule B2702
      were previously shown to bind specifically to VCAM-1. We hypothesised that
      radiolabelled B2702-p and B2702-rp might have potential for the molecular imaging
      of vascular cell adhesion molecule-1 (VCAM-1) expression in atherosclerotic
      plaques. METHODS: Preliminary biodistribution studies indicated that 125I-B2702
      rp was unsuitable for in vivo imaging owing to extremely high lung uptake. 123I-
      or 99mTc-labelled B2702-p was injected intravenously to Watanabe heritable
      hyperlipidaemic rabbits (WHHL, n=6) and control animals (n=6). After 180 min,
      aortas were harvested for ex vivo autoradiographic imaging, gamma-well counting,
      VCAM-1 immunohistology and Sudan IV lipid staining. RESULTS: Robust VCAM-1
      immunostaining was observed in Sudan IV-positive and to a lesser extent in Sudan
      IV-negative areas of WHHL animals, whereas no expression was detected in control
      animals. Significant 2.9-fold and 1.9-fold increases in 123I-B2702-p and 99mTc
      B2702-p aortic-to-blood ratios, respectively, were observed between WHHL and
      control animals (p<0.05). Tracer uptake on ex vivo images co-localised with
      atherosclerotic plaques. Image quantification indicated a graded increase in 123I
      B2702-p and 99mTc-B2702-p activities from control to Sudan IV-negative and to
      Sudan IV-positive areas, consistent with the observed pattern of VCAM-1
      expression. Sudan IV-positive to control area tracer activity ratios were 17.0+/
      9.0 and 5.9+/-1.8 for 123I-B2702-p and 99mTc-B2702-p, respectively. CONCLUSION:
      Radiolabelled B2702-p is a potentially useful radiotracer for the molecular
      imaging of VCAM-1 in atherosclerosis.

PMID- 17219136
TI  - Accuracy of 64-slice CT angiography for the detection of functionally relevant
      coronary stenoses as assessed with myocardial perfusion SPECT.
AB  - PURPOSE: CT angiography (CTA) offers a valuable alternative for the diagnosis of
      CAD but its value in the detection of functionally relevant coronary stenoses
      remains uncertain. We prospectively compared the accuracy of 64-slice CTA with
      that of myocardial perfusion imaging (MPI) using (99m)Tc-tetrofosmin-SPECT as the
      gold standard for the detection of functionally relevant coronary artery disease
      (CAD). METHODS: MPI and 64-slice CT were performed in 100 consecutive patients.
      CTA lesions were analysed quantitatively and area stenoses > or =50% and > or
      =75% were compared with the MPI findings. RESULTS: In 23 patients, MPI perfusion
      defects were found (12 reversible, 13 fixed). A total of 399 coronary arteries
      and 1,386 segments was analysed. Eighty-four segments (6.1%) in 23 coronary
      arteries (5.8%) of nine patients (9.0%) were excluded owing to insufficient image
      quality. In the remaining 1,302 segments, quantitative CTA revealed stenoses > or
      =50% in 57 of 376 coronary arteries (15.2%) and stenoses > or =75% in 32 (8.5%)
      coronary arteries. Using a cut-off at > or =75% area stenosis, CTA yielded the
      following sensitivity, specificity, negative (NPV) and positive predictive value
      (PPV), and accuracy for the detection of any (fixed and reversible) MPI defect:
      by patient, 75%, 90%, 93%, 68% and 87%, respectively; by artery, 76%, 95%, 99%,
      50% and 94%, respectively. CONCLUSION: Sixty-four-slice CTA is a reliable tool to
      rule out functionally relevant CAD in a non-selected population with an
      intermediate pretest likelihood of disease. However, an abnormal CTA is a poor
      predictor of ischaemia.

PMID- 17219137
TI  - Effects of MDMA on blood glucose levels and brain glucose metabolism.
AB  - PURPOSE: This study was designed to assess changes in glucose metabolism in rats
      administered single or repeated doses of MDMA. METHODS: Two different experiments
      were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40
      mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving
      three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a
      dedicated small-animal PET scanner 1 h after single-dose administration or 7 days
      after repeated doses. Glucose metabolism was measured in 12 cerebral regions of
      interest. Rectal temperature and blood glucose were monitored. RESULTS: Peak body
      temperature was reached 1 h after MDMA administration. Blood glucose levels
      decreased significantly after MDMA administration. In the single-dose experiment,
      brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation
      in the hippocampus, amygdala and auditory cortex. In the repeated-dose
      experiment, brain glucose metabolism did not show any significant change at day
      7. CONCLUSION: These results are the first to indicate that MDMA has the
      potential to produce significant hypoglycaemia. In addition, they show that MDMA
      alters glucose metabolism in components of the motor, limbic and somatosensory
      systems acutely but not on a long-term basis.

PMID- 17219138
TI  - Nicotine moderates the effects of macronutrient balance on nutrient intake by
      parasitized Manduca sexta L.
AB  - Effects of dietary nicotine and macronutrient ratio on M. sexta larvae were
      examined. Larvae were fed a carbohydrate-biased, protein-biased or diet having
      equal amounts of casein and sucrose, with and without nicotine. Without nicotine,
      larvae displayed compensatory feeding on the low protein diet, but despite
      consuming more, grew least on this diet. Nicotine at 0.5% had no effect on
      nutrient consumption. Nicotine at 1.0 and 2.0% reduced overall consumption and
      thereby also reduced nicotine consumption. Larvae parasitized by C. congregata
      displayed reduced nutrient intake and growth on all diets. Parasitized larvae
      responded to 1% nicotine similarly to unparasitized larvae. At 0.5% nicotine,
      they displayed reduced consumption on all diets, possibly due to altered
      chemoreceptor sensitivity to nicotine. When offered a choice of two diets having
      different macronutrient ratios, one with and the other without 0.1% nicotine, all
      larvae preferred the diet lacking nicotine and failed to regulate nutrient intake
      such that the nutrient intake target, a ratio of nutrients supporting optimal
      growth, was achieved. Parasitized larvae consumed less nicotine on a fresh weight
      basis than unparasitized insects, suggesting that the feeding response of
      parasitized larvae to nicotine minimizes the exposure of nicotine to developing
      parasites.

PMID- 17219139
TI  - Metabolic and ionoregulatory responses of the Amazonian cichlid, Astronotus
      ocellatus, to severe hypoxia.
AB  - We examined the metabolic and ionoregulatory responses of the Amazonian cichlid,
      Astronotus ocellatus, to 20 h exposure to severe hypoxia (0.37 +/- 0.19 mg
      O(2)/l; 4.6% air saturation) or 8 h severe hypoxia followed by 12 h recovery in
      normoxic water. During 20 h exposure to hypoxia, white muscle [ATP] was
      maintained at normoxic levels primarily through a 20% decrease in [creatine
      phosphate] (CrP) and an activation of glycolysis yielding lactate accumulation.
      Muscle lactate accumulation maintained cytoplasmic redox state ([NAD(+)]/[NADH])
      and was associated with an inactivation of the mitochondrial enzyme pyruvate
      dehydrogenase (PDH). The inactivation of PDH was not associated with significant
      changes in cytoplasmic allosteric modulators ([ADP(free)], redox state, or
      [pyruvate]). Hypoxia exposure caused an approximately 65% decrease in gill
      Na(+)/K(+) ATPase activity, which was not matched by changes in Na(+)/K(+) ATPase
      alpha-subunit protein abundance indicating post-translational modification of
      Na(+)/K(+) ATPase was responsible for the decrease in activity. Despite decreases
      in gill Na(+)/K(+) ATPase activity, plasma [Na(+)] increased, but this increase
      was possibly due to a significant hemoconcentration and fluid shift out of the
      extracellular space. Hypoxia caused an increase in Na(+)/K(+) ATPase alpha
      subunit mRNA abundance pointing to either reduced mRNA degradation during
      exposure to hypoxia or enhanced expression of Na(+)/K(+) ATPase alpha-subunit
      relative to other genes.

PMID- 17219140
TI  - Predicting patterns of glioma recurrence using diffusion tensor imaging.
AB  - Although multimodality therapy for high-grade gliomas is making some improvement
      in outcome, most patients will still die from their disease within a short time.
      We need tools that allow treatments to be tailored to an individual. In this
      study we used diffusion tensor imaging (DTI), a technique sensitive to subtle
      disruption of white-matter tracts due to tumour infiltration, to see if it can be
      used to predict patterns of glioma recurrence. In this study we imaged 26
      patients with gliomas using DTI. Patients were imaged after 2 years or on
      symptomatic tumour recurrence. The diffusion tensor was split into its isotropic
      (p) and anisotropic (q) components, and these were plotted on T(2)-weighted
      images to show the pattern of DTI abnormality. This was compared to the pattern
      of recurrence. Three DTI patterns could be identified: (a) a diffuse pattern of
      abnormality where p exceeded q in all directions and was associated with diffuse
      increase in tumour size; (b) a localised pattern of abnormality where the tumour
      recurred in one particular direction; and (c) a pattern of minimal abnormality
      seen in some patients with or without evidence of recurrence. Diffusion tensor
      imaging is able to predict patterns of tumour recurrence and may allow better
      individualisation of tumour management and stratification for randomised
      controlled trials.

PMID- 17219141
TI  - Uncinate fasciculus fiber tracking in mesial temporal lobe epilepsy. Initial
      findings.
AB  - In temporal lobe epilepsy (TLE) due to hippocampal sclerosis (HS), ictal
      discharge spread to the frontal and insulo-perisylvian cortex is commonly
      observed. The implication of white matter pathways in this propagation has not
      been investigated. We compared diffusion tensor imaging (DTI) measurements along
      the uncinate fasciculus (UF), a major tract connecting the frontal and temporal
      lobes, in patients and controls. Ten right-handed patients referred for
      intractable TLE due to a right HS were investigated on a 1.5-T MR scanner
      including a DTI sequence. All patients had interictal fluorodeoxyglucose PET
      showing an ipsilateral temporal hypometabolism associated with insular and
      frontal or perisylvian hypometabolism. The controls consisted of ten right-handed
      healthy subjects. UF fiber tracking was performed, and its fractional anisotropy
      (FA) values were compared between patients and controls, separately for the right
      and left UF. The left-minus-right FA UF asymmetry index was computed to test for
      intergroup differences. Asymmetries were found in the control group with right
      greater-than-left FA. This asymmetrical pattern was lost in the patient group.
      Right FA values were lower in patients with right HS versus controls. Although
      preliminary, these findings may be related to the preferential pathway of seizure
      spread from the mesial temporal lobe to frontal and insulo-perisylvian areas.

PMID- 17219142
TI  - Staging of carcinoma of the uterine cervix and endometrium.
AB  - Carcinoma of the uterine cervix and endometrium are common gynecologic
      malignancies. Both carcinomas are staged and managed by means of the
      International Federation of Gynecology and Obstetrics (FIGO) staging system. In
      uterine cervical cancer, the FIGO staging system is determined preoperatively by
      limited conventional procedures. Although this system is effective for early
      stage disease, it has inherent inaccuracies in advanced stage diseases and does
      not address nodal involvement. CT and MR imaging are widely used as comprehensive
      imaging modalities to evaluate tumor size and extent, and nodal involvement. MR
      imaging is an excellent modality for depicting invasive cervical carcinoma and
      can provide objective measurement of tumor volume, and provides high negative
      predictive value for parametrial invasion and stage IVA disease. In contrast,
      endometrial cancer is surgically staged. Beside recognition of the important
      prognostic factors, including histologic subtype and grade, accurate assessment
      of the tumor extent on preoperative MR imaging is expected to greatly optimize
      surgical procedure and therapeutic strategy. Contrast-enhanced MR imaging can
      offer "one stop" examination for evaluating the depth of myometrial invasion
      cervical invasion and nodal metastases. Evaluation of myometrial invasion on MR
      imaging may be an alternative to gross inspection of the uterus during the
      surgery.

PMID- 17219143
TI  - Interventional management of gastroduodenal lesions complicating intra-arterial
      hepatic chemotherapy.
AB  - Herein we report the efficacy of embolization of small patent gastric or duodenal
      vessels for treating gastroduodenal complications after hepatic arterial infusion
      therapy (HAIC). Catheter ports were implanted percutaneously from a femoral
      approach in three cases or surgically in the gastroduodenal artery in two cases.
      Acute abdominal pain developed on average after four HAIC courses of 5FU
      oxaliplatin, mytomycin, oxaliplatin or fotemustine. Esophagogastroduodenoscopy
      showed gastroduodenal lesions (gastroduodenitis with or without ulcerations) in
      all cases. Despite the interruption of the HAIC, symptoms persisted and led to
      selective hepatic arteriography showing a patent right gastric artery (n = 4) or
      a recanalized gastroduodenal artery (n = 1) responsible for gastroduodenal
      misperfusion. Successful embolizations of the arteries responsible for
      gastroduodenal misperfusion (right gastric artery in four cases and
      gastroduodenal artery in one case) using 0.018 platinium coils relieved the
      patients' symptoms and allowed the HAIC to continue. In gastroduodenal
      complications of HAIC, a selective hepatic arteriography should be performed to
      search any artery responsible for the misperfusion of the toxic agent in the
      gastroduodenal area. Embolization of these arteries allowed the HAIC to be
      restored.

PMID- 17219144
TI  - Reliable 5-min real-time MR technique for left-ventricular-wall motion analysis.
AB  - The aim of this study was to investigate the value of a real-time magnetic
      resonance imaging (MRI) approach for the assessment of left-ventricular-wall
      motion in patients with insufficient transthoracic echocardiography in terms of
      accuracy and temporal expenditure. Twenty-five consecutive patients were examined
      on a 1.5-Tesla whole-body MR system (ACS-NT, Philips Medical Systems, Best, NL)
      using a real-time and ECG-gated (the current gold standard) steady-state free
      precession (SSFP) sequence. Wall motion was analyzed by three observers by
      consensus interpretation. In addition, the preparation, scanning, and overall
      examination times were measured. The assessment of the wall motion demonstrated a
      close agreement between the two modalities resulting in a mean kappa coefficient
      of 0.8. At the same time, each stage of the examination was significantly
      shortened using the real-time MR approach. Real-time imaging allows for accurate
      assessment of left-ventricular-wall motion with the added benefit of decreased
      examination time. Therefore, it may serve as a cost-efficient alternative in
      patients with insufficient echocardiography.

PMID- 17219145
TI  - The effect of dose reduction and feasibility of edge-preserving noise reduction
      on the detection of liver lesions using MSCT.
AB  - The purpose of this study was to assess the effect of dose reduction and the
      potential of noise reduction filters on image quality and the detection of liver
      lesions using MSCT. Twenty-nine patients with a total of 40 liver lesions
      underwent 16-slice CT (120 kV; 180 mAs). Virtual noise was added to CT raw
      datasets simulating effective mAs levels of 155, 130, 105, 80, 55, 30 and 10 mAs.
      All datasets were post-processed with an edge-preserving noise-reduction filter
      (ANR-3D), yielding a total of 15 datasets per patient. Ten radiologists performed
      independent evaluations of image quality, the presence of liver lesions and
      diagnostic confidence. Quantitative noise and contrast-to-noise ratios (CNR) were
      obtained. Superior image quality (P < 0.02), reduction of image noise (P < 0.001)
      and the increase of lesion-to-liver CNR (P < 0.001) were observed in images
      processed with the ANR-3D filter. Sensitivity for lesion detection remained
      unchanged down to 105 mAs (CTDI(w) 6.6 mGy) without filter and 80 mAs (CTDI(w)
      5.1 mGy) with ANR-3D. Confidence was rated significantly higher for datasets
      reconstructed with ANR-3D. The use of a noise-reducing, but edge-preserving
      filter (ANR-3D) is a promising option to reduce further the radiation dose in
      liver CT.

PMID- 17219147
TI  - High-resolution MRI of the wrist and finger joints in patients with rheumatoid
      arthritis: comparison of 1.5 Tesla and 3.0 Tesla.
AB  - The goal of this study was to compare magnetic resonance (MR) image quality at
      different field strengths for evaluating lesions in wrist and finger joints of
      patients with rheumatoid arthritis (RA) in order to determine whether the higher
      field strength provides diagnostic gain. The hand mainly affected in 17 RA
      patients was examined at 1.5 Tesla (T) and 3.0 T with comparable MR imaging (MRI)
      protocols. MR images were reviewed twice by two experienced radiologists using
      the Rheumatoid Arthritis MRI Scoring System (RAMRIS) of the OMERACT (Outcome
      Measures in Rheumatoid Arthritis Clinical Trials) group. Image quality was rated
      on a five-point scale using Friedmann's test and Kendall's W-test for statistical
      analysis. Image comparison revealed better image quality at higher field
      strength. Image quality of T1-weighted images was rated 14-22% better at 3.0 T
      compared with 1.5 T by both readers. Moreover, the rating for the T2-weighted
      images acquired at 3.0 T was one point better in the five-point scale used. Inter
      reader correlation for image quality, bone erosions/defects, edema and synovitis
      ranged between 0.6 and 0.9 at 3.0 T and between 0.6 and 0.8 at 1.5 T. Intra
      reader correlation for these parameters was high at 0.8-1.0. MRI image quality of
      RA hands is superior at 3.0 T, while an acceptable image quality is achieved at
      1.5 T, which improves the evaluation of extent of bone edema, synovitis and
      identification of small bone erosions.

PMID- 17219146
TI  - Imaging of aortic abnormalities with contrast-enhanced ultrasound. A pictorial
      comparison with CT.
AB  - Aortic abnormalities are commonly encountered and may represent a diagnostic
      challenge in patients with acute or chronic clinical symptoms. Contrast-enhanced
      ultrasound (CEUS) with low mechanical index (low MI) is a new promising method in
      the diagnosis and follow-up of pathological aortic lesions. CEUS with SonoVue
      allows a more rapid and noninvasive diagnosis, especially in critical patients
      because of its bedside availability. This review compares CEUS findings with
      those documented on computed tomography angiography (CTA), allowing the reader to
      appreciate the usefulness of CEUS in this clinical situation.

PMID- 17219148
TI  - Mechanism of antitumor effect on mouse hepatocellular carcinoma by intratumoral
      injection of OK-432, a streptococcal preparation.
AB  - Intratumoral (i.t.) injection of OK-432, a streptococcal preparation, into
      implanted tumors of mouse hepatocellular carcinoma (MIH-2) showed antitumor
      effect including tumor eradication. Intraperitoneal administration of same dose
      OK-432 did not exhibit tumor suppressive effect. In vitro cytotoxic test
      suggested that direct cytotoxic effect of OK-432 was not associated with
      antitumor activity by i.t.-OK-432 treatment. It was also found that Toll-like
      receptor 4 signaling was not involved in i.t.-OK-432 treatment. Three mice out of
      five, which had shown tumor eradication by i.t.-OK-432 treatment did not reject
      re-challenge of MIH-2 cells. Splenocytes from i.t.-OK-432 treated mice did not
      produce IFN-gamma by stimulation with MIH-2 cells in vitro, but produced abundant
      IFN-gamma by stimulation with OK-432. Immunofluorescence microscopy demonstrated
      that CD4+T cells, but not CD8+T cells, infiltrated to i.t.-OK-432 treated tumor
      tissue produced IFN-gamma. Tumor-infiltrating CD4+T cells from i.t.-OK-432
      treated tumor tissue produced IFN-gamma by in vitro stimulation with OK-432
      higher than those from untreated tumor tissue. IFN-gamma directly induced
      apoptosis of MIH-2 cells in vitro. Collectively, i.t.-OK-432 treatment induced
      priming of CD4+T cells to antigenecity of OK-432, and repetitive i.t.-OK-432
      treatment induced IFN-gamma production from OK-432-sensitized CD4+T cells in
      tumor site, leading to apoptosis of MIH-2 cells susceptible to IFN-gamma.

PMID- 17219149
TI  - Monoclonal antibody 2C5-modified doxorubicin-loaded liposomes with significantly
      enhanced therapeutic activity against intracranial human brain U-87 MG tumor
      xenografts in nude mice.
AB  - Liposomes, modified with monoclonal antibodies, are suitable carriers for
      targeted delivery of chemotherapeutic drugs into brain tumors. Here, we
      investigate the therapeutic efficacy of monoclonal anticancer antibody 2C5
      modified long-circulating liposomes (LCL) loaded with doxorubicin (2C5-DoxLCL)
      for the treatment of U-87 MG human brain tumors in an intracranial model in nude
      mice. In vitro, 2C5-DoxLCL is significantly more effective in killing the U-87 MG
      tumor cells than Doxil (commercial doxorubicin-loaded PEGylated LCL) or DoxLCL
      modified with a non-specific IgG. 2C5-immunoliposomes also demonstrate a
      significantly higher accumulation in U-87 MG tumors compared to all controls in a
      subcutaneous model. The treatment of intracranial U-87 MG brain tumors in nude
      mice with 2C5-DoxLCL provides a significant therapeutic benefit over control
      formulations, substantially reducing the tumor size and almost doubling the
      survival time. Thus, monoclonal antibody 2C5-modified LCL can specifically target
      the anticancer drugs to brain tumors, leading to improved therapeutic treatment
      of brain tumor in an intracranial model, in vivo.

PMID- 17219150
TI  - Efficacy of an osmotic pump delivered, GM-CSF-based tumor vaccine in the
      treatment of upper aerodigestive squamous cell carcinoma in rats.
AB  - PURPOSE: Upper aerodigestive tract (UADT) cancer has not experienced significant
      overall survival improvement for over 20 years, and no successful treatments for
      systemic disease exist. Most patients with UADT cancer experience immune
      suppression, therefore immune restorative therapies may offer promise for these
      patients. We presently tested the efficacy of granulocyte macrophage-colony
      stimulating factor (GM-CSF) delivered via 28-day continuous infusion pump, in
      combination with irradiated tumor cells, in a flank model of UADT cancer.
      METHODS: Five groups of rats were inoculated with syngeneic mucosally derived
      squamous carcinoma cells (FAT-7). Osmotic minipumps were implanted in the
      contralateral flank to deliver GM-CSF at 0 (PBS), 0.1, 1, 10, or 100 ng/day (n =
      6 per group) for 28 days; 10(6) irradiated FAT-7 cells (ITC) were injected at the
      site of the GM-CSF infusion on days 0, 3, 7, 14, and 21 immune infiltrates in
      tumors were analyzed. RESULTS: Rats that received 10 or 100 ng/day GM-CSF/ITC had
      a significantly slower tumor growth rate compared to those who received 0, 0.1,
      or 1 ng/day (ANOVA, P < 0.01). There were increased CD 4+, CD 8+, and CD 68+
      cells in tumors of GM-CSF/ITC treated animals over controls. CONCLUSION: GM-CSF
      (10 or 100 ng/day) delivered locally via osmotic pump with ITC slows the growth
      rate of mucosally derived squamous cell carcinoma in rats while improving immune
      cell infiltrates. The efficacy of locally delivered GM-CSF immunotherapy in this
      model may be a first step toward this immunotherapy strategy for humans.

PMID- 17219151
TI  - An MVA vaccine overcomes tolerance to human p53 in mice and humans.
AB  - BACKGROUND: The cellular regulatory protein p53 is overexpressed by almost 50% of
      all malignancies making it an attractive target for a vaccine approach to cancer.
      A number of immunotherapy approaches targeting p53 have been evaluated
      successfully in murine models, but translation of these preclinical findings to
      the clinic has been unsuccessful. Prior studies in our laboratory employing
      murine models demonstrated that a modified vaccinia virus Ankara (MVA) vaccine
      expressing murine p53 could stimulate p53 specific immunity. Systemic
      administration of the MVA vaccine was able to effect the rejection of established
      tumors. To better understand the immunologic mechanisms that underlie the vaccine
      function of human p53, we utilized a murine model in which the murine germ line
      copy of p53 was replaced with a modified human one. These mice, referred to as
      Hupki, were evaluated as a tolerant model to explore the capacity of MVA
      expressing human p53 to overcome tolerance and reject human p53-expressing
      tumors. RESULTS: MVAp53 immunization of Hupki mice resulted in the generation of
      p53-specific CD8(+) T cells and the rejection of a highly aggressive murine
      mammary carcinoma cell line 4T1(H-2d) transfected with human p53 (4T1p53). An
      immunologic correlate of tumor protection was evaluated utilizing an overlapping
      peptide library spanning the full length of human p53. This reagent was also used
      in combination with MVAp53 to stimulate p53-specific CD8(+) T cell responses in
      cancer patients. CONCLUSION: These studies demonstrate the potential of MVAp53 to
      overcome tolerance to p53 for cancer immunotherapy.

PMID- 17219152
TI  - Comparison between an event-by-event Monte Carlo code, NOREC, and ETRAN for
      electron scaled point kernels between 20 keV and 1 MeV.
AB  - An event-by-event Monte Carlo code called NOREC, a substantially improved version
      of the Oak Ridge electron transport code (OREC), was released in 2003, after a
      number of modifications to OREC. In spite of some earlier work, the
      characteristics of the code have not been clearly shown so far, especially for a
      wide range of electron energies. Therefore, NOREC was used in this study to
      generate one of the popular dosimetric quantities, the scaled point kernel, for a
      number of electron energies between 0.02 and 1.0 MeV. Calculated kernels were
      compared with the most well-known published kernels based on a condensed history
      Monte Carlo code, ETRAN, to show not only general agreement between the codes for
      the electron energy range considered but also possible differences between an
      event-by-event code and a condensed history code. There was general agreement
      between the kernels within about 5% up to 0.7 r/r (0) for 100 keV and 1 MeV
      electrons. Note that r/r (0) denotes the scaled distance, where r is the radial
      distance from the source to the dose point and r (0) is the continuous slowing
      down approximation (CSDA) range of a mono-energetic electron. For the same range
      of scaled distances, the discrepancies for 20 and 500 keV electrons were up to 6
      and 12%, respectively. Especially, there was more pronounced disagreement for 500
      keV electrons than for 20 keV electrons. The degree of disagreement for 500 keV
      electrons decreased when NOREC results were compared with published EGS4/PRESTA
      results, producing similar agreement to other electron energies.

PMID- 17219153
TI  - Prediction of air temperature for thermal comfort of people in outdoor
      environments.
AB  - Current thermal comfort indices do not take into account the effects of wind and
      body movement on the thermal resistance and vapor resistance of clothing. This
      may cause public health problem, e.g. cold-related mortality. Based on the energy
      balance equation and heat exchanges between a clothed body and the outdoor
      environment, a mathematical model was developed to determine the air temperature
      at which an average adult, wearing a specific outdoor clothing and engaging in a
      given activity, attains thermal comfort under outdoor environment condition. The
      results indicated low clothing insulation, less physical activity and high wind
      speed lead to high air temperature prediction for thermal comfort. More accurate
      air temperature prediction is able to prevent wearers from hypothermia under cold
      conditions.

PMID- 17219154
TI  - Initial investigation of the infertile couple. Pre-clinic request of
      investigations to facilitate diagnosis: utilising the waiting time to minimise
      delay.
AB  - OBJECTIVE: To evaluate the effectiveness of pre-clinic request of investigations
      to facilitate diagnosis in couples referred to the infertility clinic and to
      assess patient satisfaction of the concept. STUDY DESIGN: Prospective cohort
      study with analysis of patient satisfaction questionnaire. Investigation packs
      were sent to patients in advance of their clinic appointment. These contained
      written explanation about various fertility tests to enable patients to have
      investigations before their first clinic appointment. The results should then be
      available at the time of consultation enabling a diagnosis to be made at their
      first clinic visit. RESULTS: Eighty percent (43/54) of couples had completed all
      the investigations requested by the time of their clinic appointment. The full
      investigation results of 41 couples were available at the time of consultation.
      From the available results, a diagnosis could be reached in 76% of couples at the
      first clinic visit. Twenty-three percent of couples were not happy with the
      concept of pre-clinic investigation and would prefer to come to clinic first to
      discuss these tests, even if that meant a delay in diagnosis. There appears to be
      a trend in age, with those who were satisfied with the concept of pre-clinic
      investigation being older. Older women seem to have an increasing sense of
      urgency with advancing age. CONCLUSION: While the concept of pre-clinic request
      of investigations may not be suitable for every couple it does allow for early
      initiation of treatment in selected patients.

PMID- 17219155
TI  - Efficacy and safety of six hourly vaginal misoprostol versus intracervical
      dinoprostone: a randomized controlled trial.
AB  - OBJECTIVE: To compare the efficacy and safety of intravaginal misoprostol versus
      dinoprostone cervical gel for cervical ripening and labour induction. METHODS: We
      carried out an experimental clinical trial in which we enrolled 130 cervical
      consecutive patients with cervical ripening, randomly assigned to one of the
      following two treatment groups: (1) intravaginal misoprostol and (2)
      intracervical dinoprostone gel. A total of 50 microm of misoprostol was placed in
      the posterior vaginal fornix every 6 h for a maximum period of 24 h and 0.5 mg of
      dinoprostone was administrated in the uterine cervix every 6 h, for a maximum
      period of 24 h. The primary outcome measure was the number (rate) of women who
      went to vaginally deliver within 24 h of the protocol initiation. RESULTS: Among
      130 patients evaluated, 65 were allocated to the misoprostol group and 65 to the
      dinoprostone group. The proportion of vaginal delivery within 24 h was
      significantly higher in the misoprostol group (75%) than in the dinoprostone
      group (53.8%) (RR = 1.40, 95% CI [1.07-1.45], P = 0.02). There was no significant
      difference between the mean time interval of delivery in the misoprostol group
      and the dinoprostone group (14.9 vs.15.8 h) (P = 0.51). The Bishop score was
      significantly higher in the misoprostol group, 6 h after the onset of the study
      (1.38; relative risk, 95% CI [1.02-1.85], P = 0.03). The Caesarean delivery rate
      for fetal distress was higher in the dinoprostone group (21 vs. 10.8%, P = 0.15).
      The tachysystole (Misoprostol 6.1% vs. dinoprostone 4.6%, relative risk 1.15, 95%
      CI [0.6-2.24]) and hyperstimulation syndrome rates (Misoprostol 7.6% vs.
      dinoprostone 4.6%, relative risk 1.26, 95% CI [0.72-2.24]) were slightly
      increased in the misoprostol group than in the dinoprostone group without
      reaching the level of statistical signification. CONCLUSION: Misoprostol as used
      in this protocol is more effective than cervical dinoprostone gel application in
      the cervical ripening and labour induction. There is a tendency for an increase
      in the rate of tachysystole and hyperstimulation syndrome.

PMID- 17219156
TI  - XI VOCAL (eXtended Imaging VOCAL): a new modality for three-dimensional
      sonographic volume measurement.
AB  - INTRODUCTION: The important technological evolutions that three-dimensional
      ultrasonography devices have gone through in the last years have brought great
      benefits for the volumetric measurement of fetal organs and structures. In
      clinical practice, three-dimensional volumetry has helped to identify
      abnormalities in fetal compartment and other related organs, assisting in the
      diagnosis and risk estimation of several pathological conditions in fetal
      medicine. AIM: The authors describe a new methodology for volumetric calculation
      through three-dimensional ultrasonography called eXtended Imaging VOCAL (XI
      VOCAL), which is part of the software Three-dimensional eXtended Imaging (3DXI).
      This software virtualizes real organs, by analyzing the volume through a diagram
      of slice sections (Multi-slice view) that simultaneously shows a sequence of
      images in parallel planes, and establishes the volume of the organ. Because of
      the importance of accurate volumetric measurements in obstetric ultrasonography,
      a new method allowing this measurement should be regarded as of great interest.

PMID- 17219157
TI  - Successful outcome following pre-viability amniorrhexis.
AB  - A 34-years-old primigravida conceived following a fourth attempt at in vitro
      fertilization and embryo transfer for severe bilateral tubal disease and grade IV
      endometriosis. Pregnancy progressed well until 17 weeks gestation when she
      spontaneously ruptured her membranes. She elected to continue with the pregnancy
      despite the significant risks associated with prolonged rupture of membranes
      (PROM) and anhydramnion at extremes of viability. Pregnancy was carried to 28
      weeks gestation, when delivery was necessitated by a major antepartum haemorrhage
      following abruption placentae. A male infant weighing 1,100 g was delivered by
      emergency caesarean section in good condition, and with no features
      oligohydramnion tetrad (Potter's features, skeletal deformities, intrauterine
      growth restriction, and pulmonary hypoplasia). This case adds to the small number
      of cases in the literature of successful outcome following prolonged pre
      viability PROM. Counselling and psychological support to the parents in this
      situation is extremely important since the anxiety and uncertainty associated
      with expectant management of PROM does not end with the "successful" delivery of
      the baby but persists all through the neonatal period and for several years
      later.

PMID- 17219158
TI  - Perinatal outcomes of pregnancies with borderline amniotic fluid index.
AB  - OBJECTIVE: Our aim was to determine whether a borderline amniotic fluid index
      observed during antepartum testing confers a significant risk of adverse
      perinatal outcome. METHODS: Between April 2001 and May 2005, uncomplicated
      gestations with a singleton non-anomalous fetus, who underwent weekly monitoring
      of amniotic fluid index (AFI) until delivery during the last trimester and who
      gave birth at our hospital, were identified for our study. Normal amniotic fluid
      volume and borderline amniotic fluid were defined as AFI of >10 and <24 cm and >5
      and <10 cm, respectively. The groups were compared on maternal data, mode of
      delivery and perinatal outcomes such as fetal distress, intrauterine growth
      restriction and meconium fluid. RESULTS: A total of 90 cases were identified as
      borderline amniotic fluid and 277 cases as normal AFI. We observed significant
      increased incidences of admission to neonatal intensive care unit, intrauterine
      growth restriction, meconium-stained amniotic fluid, intrapartum fetal distress
      in the group with borderline amniotic index (P < 0.05). CONCLUSIONS: A borderline
      amniotic fluid index observed in antepartum testing during the last trimester
      carries an increased risk of adverse perinatal outcomes. These patients should be
      followed up carefully during the antepartum and intrapartum period.

PMID- 17219159
TI  - Trauma in pregnancy.

PMID- 17219160
TI  - Polymyositis in a patient with recurring ovarian cancer and history of unrelated
      breast cancer.
AB  - BACKGROUND: Polymyositis (PM) is an idiopathic inflammatory myopathy.
      Occasionally, it may present as a paraneoplastic syndrome and it is strongly
      associated with ovarian and weakly with breast cancer. We present here a case of
      a 60-year-old patient with sequential breast and ovarian (second primary)
      carcinomas followed by PM as a paraneoplastic disorder. CASE REPORT: The patient
      had been diagnosed with stage I breast carcinoma 3 years ago and had been treated
      with conservative surgery followed by radiotherapy and six cycles of chemotherapy
      (CMF). One and a half year later an ovarian carcinoma was diagnosed for which the
      patient underwent abdominal hysterectomy oophorectomy and omentectomy. The
      pathological report characterized it as second primary. Adjuvant chemotherapy
      with carboplatin and taxol was administered. Fourteen months after the initial
      laparotomy, the patient was re-operated due to ovarian carcinoma recurrence which
      was involving all lesser pelvis organs. After a successful radical removal of the
      recurrence the patient developed a fully expressed PM. This case serves to remind
      that this disease can occur as a paraneoplastic disorder.

PMID- 17219161
TI  - Diagnosis of uteroperitoneal fistula through color Doppler hysterosonography.
AB  - INTRODUCTION: Uterine fistulas are infrequent pathologic entities characterized
      by abnormal communication of the uterus with any other organ or structure through
      a perforation formed due to traumatic and infectious conditions among others. The
      use of hysterosonography as method of diagnosis for that pathologic entity has
      few descriptions in medical literature. MEDLINE search resulted in only two cases
      reporting the use of HS in the diagnosis of uterine fistula. OBJECTIVE: Our
      objective is to report a case of uteroperitoneal fistula caused by uterine trauma
      during curettage, diagnosed by color Doppler hysterosonogrphy. The importance of
      our report lies on HS as a simple, safe and low cost method, which can be used
      for the diagnosis of fistulous processes involving the uterus.

PMID- 17219162
TI  - Transfascial vaginal tape (TFT): a simple, safe and cost-effective procedure for
      stress urinary incontinence. A preliminary study.
AB  - OBJECTIVE: To analyse prospectively the effectiveness of a new simple, minimally
      invasive, and cost-effective technique for the treatment of female urinary stress
      incontinence: the transfascial vaginal tape (TFT). MATERIALS AND METHODS: In a
      prospective study, we enrolled 45 women undergoing TFT with or without
      hysterectomy and/or another pelvic reconstructive procedure between 1st December
      2003 and 31st December. TFT consists of a tension-free urethrosuspension using a
      sling located at the mid-urethral level and placed laterally in the endopelvic
      fascia previously perforated. Follow-up evaluations were established at 3 and 6
      months and at 1 year after the operation. During each follow-up, women underwent
      cough stress test and they answered to the "Incontinence quality of life
      questionnaire" (I-QOL), to the Patient Global Impression of Severity (PGI-S) and
      of Improvement (PGI-I) questions. RESULTS: Thirty-nine patients (88.9%) had a
      follow-up examination 1 year after surgery. Of these, 30 (76.9%) were defined
      cured, 6 (15.4%) improved and 3 (7.7%) failed. CONCLUSIONS: TFT procedure can be
      considered a simple, safe and cost-effective procedure for the treatment of
      stress urinary incontinence and can be an alternative to tension-free vaginal
      tape or transobturator route for sub-urethral tape procedures.

PMID- 17219163
TI  - Arias-Stella reaction in upper genital tract in pregnant and non-pregnant women:
      a study of 120 randomly selected cases.
AB  - AIMS: 1. To study the diagnostic importance of the Arias-Stella reaction. 2. To
      study tubal epithelial changes in ectopic pregnancy. 3. To study the occurrence
      of Arias-Stella reaction in non-pregnant women receiving hormonal treatment.
      METHODS: A prospective study was conducted on 120 patients who underwent
      endometrial curettage and/or salpingectomy. The patients were divided into four
      groups, each comprising of 30 patients. Groups 1 and 4 included non-pregnant
      patients who were being evaluated for infertility and dysfunctional uterine
      bleeding respectively, while pregnant patients were included in Group 2 (intra
      uterine abortions) and Group 3 (ectopic tubal gestation). The endometrial
      curettings and fallopian tube lining epithelial cells were examined for the
      changes described by Arias-Stella. Cases which showed the presence of the Arias
      Stella reaction were further classified. RESULTS: The changes of the Arias-Stella
      reaction in endometrial glands were observed in 80% cases of intra-uterine
      abortions. Secretory/hypersecretory pattern was the most commonly observed type
      (36.67%). The reaction was seen in 3.33% each of patients evaluated for
      infertility and patients on hormonal therapy with oral progestational agents for
      the management of dysfunctional uterine bleeding. Although uncommon, the Arias
      Stella reaction was noted in the epithelium of fallopian tubes (16.67%) from
      patients with ectopic tubal gestation. CONCLUSION: The findings of the present
      study emphasize the diagnostic importance of the Arias-Stella reaction. The
      changes of the reaction are a histological clue to the presumptive diagnosis of
      the presence of chorial tissue in cases in which the chorionic material is not
      found in the endometrial biopsy. The morphological features can be mistaken for
      malignancy if the pathologist is not aware of the patient's pregnancy or history
      of hormonal intake.

PMID- 17219164
TI  - Safe fertility-preserving management in gynecological malignancies.
AB  - OBJECTIVE: To provide a review in the available literature about the safe
      fertility-preserving management in gynecological malignancies, focusing on the
      selection criteria of the patients, treatment options and follow-up. DESIGN:
      Literature survey. RESULTS: The incidence of cancer in women who still want to
      get pregnant is increasing significantly. An early detection in gynecological
      malignancies allows less aggressive approaches to cure such disorders. A more
      conservative management, which preserves fertility, is considered safe and an
      option for those who have not completed their child-bearing. CONCLUSIONS:
      Selected patients with cervical, endometrial and ovarian cancer may be candidates
      to a safe fertility-preserving management. A careful stage and follow-up of the
      patients is essential to achieve success with this practice.

PMID- 17219165
TI  - An investigation of the peroxidase activity of Vitreoscilla hemoglobin.
AB  - In order to investigate the ability of the Vitreoscilla hemoglobin (VHb) to act
      as a peroxidase, the protein was overexpressed in Escerichia coli and purified
      using a 6xHis-tag. The peroxidase activity of VHb was studied using 2,2'
      azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferrocene carboxylic
      acid (FcCOOH) dopamine and L-dopa as substrates. The effects of external agents
      such as pH, salt concentration/ionic strength, and the thermal stability of VHb
      on the catalytic activity were assessed. The optimum pH for VHb using ABTS as a
      substrate was estimated to be 6-7. The VHb protein proved to be stable up to 80
      degrees C, as judged by its peroxidase activity. Furthermore, NaCl concentrations
      up to 100 mM did not exert any significant effect on the activity. The catalytic
      activity against ABTS and FcCOOH was similar to that measured for horseradish
      peroxidase, whereas in the case of the phenolic substrates dopamine and L-dopa
      the activity was several orders of magnitude lower. The Michaelis constants,
      KmH2O2, were in good agreement with the data for human and bovine hemoglobin. No
      activity could be detected for the negative controls lacking VHb. These results
      demonstrate that VHb exhibits peroxidase activity, a finding in line with the
      hypothesis that VHb has cellular functions beyond the role as an oxygen carrier.

PMID- 17219166
TI  - Intense hypoxic cycle exercise does not alter lung density in competitive male
      cyclists.
AB  - We tested the hypothesis that intense short duration hypoxic exercise would
      result in an increase in extravascular lung water (EVLW), as evidenced by an
      increase in lung density. Using computed tomography (CT), baseline lung density
      was obtained in eight highly trained male cyclists (mean +/- SD: age = 28 +/- 8
      years; height = 180 +/- 9 cm; mass = 71.6 +/- 8.2 kg; VO2max= 65.0 +/- 5.2 ml kg
      min(-1)). Subjects then completed an intense hypoxic exercise challenge on a
      cycle ergometer and metabolic data, HR and %S(p)O2 were recorded throughout.
      While breathing 15% O2, subjects performed five 3 km cycling intervals (mean
      power, 286 +/- 20 W; HR = 91 +/- 4% HRmax) separated by 5 min of recovery. From a
      resting hypoxic S(p)O2 of 92 +/- 4%, subjects further desaturated during exercise
      to 76 +/- 3%. CT scans were repeated 76 +/- 10 min (range 63-88 min) following
      the completion of exercise. There was no change in lung density from pre (0.18 +/
      0.02 g ml(-1)) to post-exercise (0.18 +/- 0.04 g ml(-1)). The substantial
      reduction in S(p)O2 may be explained by a number of potential mechanisms,
      including decreased pulmonary diffusion capacity, alveolar hypoventilation,
      reduced red cell transit time, ventilation/perfusion inequality or a temperature
      and pH induced rightward-shift in the oxyhaemoglobin dissociation curve.
      Alternatively, the integrity of the blood gas barrier may have been disrupted
      without any measurable increase in lung density.

PMID- 17219167
TI  - Small trials focusing on surrogate end points may be uninformative.

PMID- 17219168
TI  - Relations between psychometric profiles and cardiovascular autonomic regulation
      in physical education students.
AB  - This study was designed to investigate physical education (PE) students the link
      between mood disturbances, caused by psychological or physical stressors
      associated with studying, and the autonomic nervous system modifications. PE
      students completed the profile of mood state (POMS) questionnaire at the end of
      the university year. Heart rate variability (HRV) was then measured during a head
      up tilt test (HUT) in those with the highest and lowest total mood disturbance
      (TMD) scores on three successive POMS. Among the 218 students who completed the
      POMS (85 female and 137 male), 65 had high TMD scores, suggesting mood
      disturbances and fatigue. The final sample included 12 subjects in the
      potentially overtrained (POT) group and 16 subjects in the control (CTL) group. A
      greater decrease of two indices of the autonomic system (SD1 and RMSSD) was
      observed during the HUT in the POT than in the CTL group (P < 0.05). The
      depression (Dep) and vigor (Vig) subscales of POMS were correlated with several
      HRV indices. More specifically, in the POT group, the Vig score was correlated
      with autonomous activity in the supine position, and the Dep score with
      percentages of change of sympatho-vagal activity during the HUT. This suggests
      that (1) POT students could present a weaker autonomic response to HUT, (2) Dep
      and Vig subscales of the POMS questionnaire may indicate autonomic
      dysregulations.

PMID- 17219169
TI  - Cold-induced vasodilatation is not homogenous or generalizable across the hand
      and feet.
AB  - Cold-induced vasodilatation (CIVD), a paradoxical cyclical increase in finger
      temperature upon cold exposure, is assumed to serve against cold injury. Most
      existing research has focused on hand and finger responses, yet most cold
      injuries occur in the feet. We investigated if CIVD responses of one finger can
      predict the responses of other fingers, and also whether the fingers could
      predict CIVD responses of the feet and toes. Ten subjects immersed their left
      hand up to the wrist in 8 degrees C water for 30 min. They passively rewarmed for
      15 min, followed by immersion of the left foot to the ankle in 8 degrees C water
      for 30 min. Digit temperature at the edge of the nail bed was recorded on all
      fingers and toes and on the hand and feet. In all subjects, toe and foot
      temperature gradually decreased exponentially from approximately 31 to
      approximately 9 degrees C. No subject exhibited CIVD in any toe or on the foot
      itself. Eight subjects exhibited CIVD (>1 degrees C temperature increase) in at
      least one digit of the hand, but no consistent pattern existed in finger response
      to cold. No subject had strong (>2.0 degrees C) CIVD in all fingers. Five had
      strong CIVD in some but not all digits, with magnitudes ranging 1.4-7.5 degrees
      C, while three had weak (<2 degrees C) CIVD in some but not all digits. Four
      exhibited asynchronous CIVD in the fingers, with cycles beginning at different
      times. We conclude that CIVD is highly variable across the fingers, and is not a
      generalizable response across digits or limbs.

PMID- 17219170
TI  - The effect of rate of force development on maximal force production: acute and
      training-related aspects.
AB  - The force generated during a maximal voluntary contraction (MVC) is known to
      increase by resistance training. Although this increase cannot be solely
      attributed to changes in the muscle itself, many studies examining muscle
      activation at peak force failed to detect neural adaptations with resistance
      training. However, the activation prior to peak force can have an impact on
      maximal force generation. This study aims at investigating the role of rate of
      force development (RFD) on maximal force during resistance training. Fourteen
      subjects carried out 5 days of isometric resistance training with dorsiflexion of
      the ankle with the instruction to generate maximal force. In a second experiment,
      18 subjects performed the same task with the verbal instruction to generate
      maximal force (instruction I) and to generate force as fast and forcefully as
      possible (instruction II). The main findings were that RFD increased twice as
      much as the 16% increase in maximal force with training, with a positive
      association between RFD and force within the last session of training and between
      training sessions. Instruction II generated a higher RFD than instruction I, with
      no difference in maximal force. These findings suggest that the positive
      association between RFD and maximal force is not causal, but is mediated by a
      third factor. In the discussion, we argue for the third factor to be
      physiological changes affecting both aspects of a MVC or different processes
      affecting RFD and maximal force separately, rather than a voluntary strategic
      change of both aspects of MVC.

PMID- 17219171
TI  - Favorable effects of non-instrumental resistance training on fat distribution and
      metabolic profiles in healthy elderly people.
AB  - This study examined the effect of a 12-week non-instrumental resistance training
      program using body weight as a load (RT-BW) on body composition, fat distribution
      and metabolic profiles in elderly males and females. Healthy, non-diabetic,
      elderly volunteers (22 males and 30 females) aged 65-82 years were non-randomly
      divided into RT-BW (12 males and 20 females) and control (10 males and 10
      females) groups. The RT-BW subjects were trained three times per week for 12
      weeks according to a specified protocol involving a combination of upper and
      lower body weight and rubber tubing exercises. We evaluated body composition and
      fat distribution using anthropometry, dual energy X-ray absorptiometry and
      ultrasonography, and measured serum lipid levels and HbA(1c) at baseline and
      after 12 weeks of training. Changes over 12 weeks were significantly greater in
      the RT-BW group compared with the control group, with a decrease in waist
      circumference, pre-peritoneal (visceral) fat thickness and thigh fat thickness,
      and an increase in thigh muscle thickness. On the other hand, the changes in body
      weight, fat mass and fat free mass were no different between the groups. Further,
      there were significantly greater changes of metabolic profiles in the RT-BW group
      with an increase in HDL cholesterol and a decrease in triglyceride and HbA(1c).
      There was a significant between-group difference in diastolic blood pressure.
      Relatively short-term, non-instrumental resistance training using body weight as
      a load was effective in improving fat distribution and metabolic profiles in
      healthy elderly people without weight loss.

PMID- 17219172
TI  - Supplemental oxygen and muscle metabolism in mitochondrial myopathy patients.
AB  - Patients with mitochondrial myopathy (MM) have a reduced capacity to perform
      exercise due to a reduced oxidative capacity. We undertook this study to
      determine whether skeletal muscle metabolism could be improved with oxygen
      therapy in patients with MM. Six patients with MM and six controls, matched for
      age, gender and physical activity, underwent (31)P-magnetic resonance
      spectroscopy ((31)P-MRS) examination. (31)P-MR spectra were collected at rest and
      in series during exercise and recovery whilst breathing normoxic (0.21 O(2)) or
      hyperoxic (1.0 O(2)) air. At rest, MM showed an elevated [ADP] (18 +/- 3
      micromol/l) and pH (7.03 +/- 0.01) in comparison to the control group (12 +/- 1
      micromol/l, 7.01 +/- 0.01) (P < 0.05) consistent with mitochondrial dysfunction.
      Oxygen supplementation did not change resting metabolites in either MM or the
      control group (P > 0.05). Inferred maximal ATP synthesis rate improved by 33%
      with oxygen in MM (21 +/- 3 vs. 28 +/- 5 mmol/(l min), P < 0.05) but only
      improved by 5% in controls (40 +/- 3 vs. 42 +/- 3 mmol/(l min), P > 0.05). We
      conclude that oxygen therapy is associated with significant improvements in
      muscle metabolism in patients with MM. These data suggest that patients with MM
      could benefit from therapies which improve the provision of oxygen.

PMID- 17219173
TI  - Biologically relevant sex differences for fitness-related parameters in active
      octogenarians.
AB  - The number of elderly people is growing in western populations, but only few
      maximal performance data exist for people >75 years, in particular for European
      octogenarians. This study was performed to characterize maximal performance of 55
      independently living subjects (32 women, 81.1 +/- 3.4 years; 23 men, 81.7 +/- 2.9
      years) with a focus on sex differences. Maximal performance was determined in a
      ramp test to exhaustion on a bicycle ergometer with ergospirometry,
      electrocardiogram and blood lactate measurements. Maximal isometric extension
      strength of the legs (MEL) was measured on a force platform in a seated position.
      Body composition was quantified by X-ray absorptiometry. In >25% of the subjects,
      serious cardiac abnormalities were detected during the ramp test with men more
      frequently being affected than women. Maximal oxygen consumption and power output
      were 18.2 +/- 3.2 versus 25.9 +/- 5.9 ml min(-1) kg(-1) and 66 +/- 12 versus 138
      +/- 40 W for women versus men, with a significant sex difference for both
      parameters. Men outperformed women for MEL with 19.0 +/- 3.8 versus 13.6 +/- 3.3
      N kg(-1). Concomitantly, we found a higher proportion of whole body fat in women
      (32.1 +/- 6.2%) compared to men (20.5 +/- 4.4%). Our study extends previously
      available maximal performance data for endurance and strength to independently
      living European octogenarians. As all sex-related differences were still apparent
      after normalization to lean body mass, it is concluded that it is essential to
      differentiate between female and male subjects when considering maximal
      performance parameters in the oldest segment of our population.

PMID- 17219174
TI  - Monitoring for overreaching in rugby league players.
AB  - The aim of this study was to identify indicators of non-functional overreaching
      (NFOR) in team sport athletes undertaking intensive training loads. Eighteen semi
      professional rugby league players were randomly assigned into two pair matched
      groups. One group completed 6 weeks of normal training (NT) whilst the other
      group was deliberately overreached through intensified training (IT). Both groups
      then completed the same 7-day stepwise training load reduction taper. Multistage
      fitness test (MSFT) performance, VO2 (max), peak aerobic running velocity (V
      (max)), maximal heart rate, vertical jump, 10-s cycle sprint performance and body
      mass were measured pre- and post-training period and following the taper.
      Hormonal, haematological and immunological parameters were also measured pre
      training and following weeks 2, 4 and 6 of training and post-taper. MANOVA for
      repeated measures with contrast analysis indicated that MSFT performance and VO2
      (max) were significantly reduced in the IT group over time and condition,
      indicating that a state of overreaching was attained. However, the only
      biochemical measure that was significantly different between the IT and NT group
      was the glutamine to glutamate (Gln/Glu) ratio even though testosterone,
      testosterone to cortisol (T/C) ratio, plasma glutamate, and CK activity were
      significantly changed after training in both groups. Positive endurance and power
      performance changes were observed post-taper in the IT group confirming NFOR.
      These changes were associated with increases in the T/C ratio and the Gln/Glu
      ratio and decreases in plasma glutamate and CK activity. These results indicate
      that although there was no single reliable biochemical marker of NFOR in these
      athletes, the Gln/Glu ratio and MSFT test may be useful measures for monitoring
      responses to IT in team sport athletes.

PMID- 17219175
TI  - Developmentally regulated histone modifications in Drosophila follicle cells:
      initiation of gene amplification is associated with histone H3 and H4
      hyperacetylation and H1 phosphorylation.
AB  - We have used gene amplification in Drosophila follicle cells as a model of
      metazoan DNA replication to address whether changes in histone modifications are
      associated with replication origin activation. We observe that replication
      initiation is associated with distinct histone modifications. Acetylated lysines
      K5, K8, and K12 on histone H4 and K14 on histone H3 are specifically enriched
      during replication initiation at the amplification origins. Strikingly, H4
      acetylation persists at an amplification origin well after replication forks have
      progressed significantly outward from the origin, indicating that H4 acetylation
      is associated with origin regulation and not histone deposition at the
      replication forks. Origin recognition complex subunit 2 (orc2) mutants with
      severe amplification defects do not abolish H4 acetylation, whereas the dup/cdt1
      mutant delays the appearance of acetylation foci, and mutants in rbf result in
      temporal persistence. These data indicate that core histone acetylation is
      associated with origin activity. Furthermore, follicle cells undergoing gene
      amplification exhibit high levels of histone H1 phosphorylation. The patterns of
      H1 phosphorylation provide insights into cell cycle states during amplification,
      as H1 kinase activity in follicle cells is responsive to high Cyclin E activity,
      and it can be abolished by overexpressing the retinoblastoma homolog, Rbf, that
      represses Cyclin E. These data suggest that amplification origins are able to
      initiate when the cells are in a late S-phase, when the genome is normally not
      licensed for replication.

PMID- 17219176
TI  - Comparison of the Z and W sex chromosomal architectures in elegant crested
      tinamou (Eudromia elegans) and ostrich (Struthio camelus) and the process of sex
      chromosome differentiation in palaeognathous birds.
AB  - To clarify the process of avian sex chromosome differentiation in palaeognathous
      birds, we performed molecular and cytogenetic characterization of W chromosome
      specific repetitive DNA sequences for elegant crested tinamou (Eudromia elegans,
      Tinamiformes) and constructed comparative cytogenetic maps of the Z and W
      chromosomes with nine chicken Z-linked gene homologues for E. elegans and ostrich
      (Struthio camelus, Struthioniformes). A novel family of W-specific repetitive
      sequences isolated from E. elegans was found to be composed of guanine- and
      cytosine-rich 293-bp elements that were tandemly arrayed in the genome as
      satellite DNA. No nucleotide sequence homologies were found for the
      Struthioniformes and neognathous birds. The comparative cytogenetic maps of the Z
      and W chromosomes of E. elegans and S. camelus revealed that there are partial
      deletions in the proximal regions of the W chromosomes in the two species, and
      the W chromosome is more differentiated in E. elegans than in S. camelus. These
      results suggest that a deletion firstly occurred in the proximal region close to
      the centromere of the acrocentric proto-W chromosome and advanced toward the
      distal region. In E. elegans, the W-specific repeated sequence elements were
      amplified site-specifically after deletion of a large part of the W chromosome
      occurred.

PMID- 17219177
TI  - [Introduction to the topic: bacterial keratitis. From the proven to the new].

PMID- 17219178
TI  - [Retinal angiomatosis. Ocular manifestation of von Hippel-Lindau disease].
AB  - Von Hippel-Lindau disease (VHL disease) is a rare multisystem disorder of
      autosomal dominant inheritance with high penetrance. Inactivation of the VHL
      protein leads to an increased expression of hypoxia induced growth factors.
      Predilection sites for tumor growth are the retina, the central nervous system
      and various visceral organs. Retinal capillary hemangioblastoma is one of the
      earliest manifestations of VHL disease. The lifetime risk of permanent visual
      loss defined as a visual acuity of 0.5 or less is about 35% in gene carriers. It
      increases to 60% if there is already retinal capillary hemangioblastoma. If VHL
      disease is suspected, a careful ophthalmological examination should be included
      in the clinical screening program. Having confirmed the diagnosis, regular
      ophthalmoscopic monitoring is essential in order to detect developing tumors at
      an early stage. Therapeutic options for small to medium sized peripheral tumors
      are laser or cryocoagulation; larger- hemangioblastomas can be treated by
      brachytherapy using ruthenium plaques, while asymptomatic juxtapapillary tumors
      can be observed at regular intervals.

PMID- 17219179
TI  - [Bacterial keratitis. Current diagnostic aspects].
AB  - Keratitis remains the third most common etiology for blindness worldwide. Whereas
      bacteria still predominate as causative organisms in temperate climates, fungal
      and mixed infections are more common in tropical and semitropical areas. In
      recent years, a shift in the causative organisms, as well as predisposing
      factors, has been reported. Risk factors that may have gained in importance, such
      as wearing contact lenses and corneal surgery, have been identified.
      Microorganisms, especially Pseudomonas spp. and mycobacteria have been frequently
      isolated in these patients. A changing pattern in microorganism infection has
      been observed that might be caused by inappropriate use of potent antimicrobial
      agents. Because of the sight threatening nature of bacterial keratitis, proper
      diagnosis and antibiotic selection are required. Management should be guided by
      the appropriate diagnosis, severity of clinical symptoms and underlying risk
      factors. Molecular techniques, such as polymerase chain reaction, have increased
      our diagnostic options, even when they cannot replace established procedures.
      This article reviews the current data and procedures available for the diagnosis
      of bacterial keratitis.

PMID- 17219180
TI  - [Ocular toxocariasis. From biology to therapy].
AB  - Ocular toxocariasis represents an organ manifestation of the systemic infection
      with the Nematode larva Toxocara canis. The infection can provoke very different
      changes in the eye. Especially posterior uveitis, vitreous body infiltrates,
      epiretinal membranes and suberetinal granulomas can occur. The diagnosis of these
      changes can be difficult due to the variety of the symptoms and on the other side
      by the absence of characteristic specific changes. Moreover unclear findings can
      occur when only serological examinations are performed. In unclear cases the
      antibody-detection by means of ELISA from the vitreous body fluid can be useful.
      The examination of vitreous body material can prove toxocara infection when no
      systemic signs of infection are present and no antibodies are detectable in the
      serum. Besides the systemic anti-helminthic therapy with Albendazol the pars
      plana vitrectomy is a substantial therapeutic option in ocular toxocariasis when
      vitreo-retinal complications are present. A well timed adequate therapy can
      stabilize the visual acuity in many cases.

PMID- 17219181
TI  - Fatigue, emotional exhaustion and perceived health complaints associated with
      work-related characteristics in employees with and without chronic diseases.
AB  - OBJECTIVES: Ageing of the Dutch working force and increasingly more stringent
      restrictions regarding early retirement and disability benefits are leading to
      higher numbers of workers with ill health. Until now, only a few studies have
      explored how employees with ill health perceive their work. This study
      investigated possible differences in scores on fatigue, emotional exhaustion,
      perceived health complaints and various work-related characteristics between
      chronically ill (CIWs) and non-chronically ill workers (NCIWs), as well as
      differences in associations between work- and health-related characteristics.
      METHODS: A questionnaire was sent to all employees of a Dutch university to
      collect data on perceived work-related and health-related characteristics
      (response 49.1%). Differences in various scores were analysed using chi (2)-tests
      and the general linear model. Associations between the work- and the health
      related characteristics were determined by multiple linear regression analyses in
      the CIWs (n = 444) and NCIWs (n = 1,347) separately. Interaction terms were
      included to detect differences between the two groups. RESULTS: The results
      indicated that the CIWs had less favourable scores on the three health-related
      characteristics. Also, the CIWs scored less favourably than the NCIWs on almost
      all the work-related characteristics. In the two groups, negative work-related
      aspects, such as higher work pressure, contributed most to explaining the
      variance in the health-related characteristics. However, in the CIWs, fatigue was
      not explained by the work-related aspects as much as in the NCIWs. In the CIWs,
      the association between unpleasant treatment and the health-related
      characteristics was stronger than in the NCIWs, but there were indications that
      autonomy, possibilities for learning and social support from superiors also
      played an important role. CONCLUSIONS: CIWs perceived more fatigue, emotional
      exhaustion and health complaints than NCIWs. There were different patterns of
      associations between work- and health-related characteristics in the NCIWs and
      CIWs. Future studies on associations between work-related characteristics and
      health should take the presence of chronic disease into account.

PMID- 17219182
TI  - Transplacental exposure of neonates to perfluorooctanesulfonate and
      perfluorooctanoate: a pilot study.
AB  - OBJECTIVES: Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) can be
      released of perfluorinated compounds by biotic and/or metabolic decomposition.
      Due to their ubiquitous occurrence, persistence and bioaccumulative properties
      they can be found in blood of the general population all over the world. In
      animal studies PFOS and PFOA provoked cancer and showed developmental toxic
      potential besides other adverse health effects. On the basis of the comparison of
      maternal and umbilical cord plasma sample pairs we wanted to examine whether
      infants are exposed to PFOS and PFOA via their mothers' blood. METHODS: We
      determined PFOS and PFOA in 11 plasma samples of mothers and the 11 corresponding
      cord plasma samples of neonates. An analytical method based on plasma protein
      precipitation followed by HPLC with MS/MS-detection was employed. As internal
      standards we used 1,2,3,4-(13)C(4)-PFOS and 1,2-(13)C(2)-PFOA. RESULTS: We found
      PFOS and PFOA in every plasma sample analysed. In maternal plasma samples PFOS
      concentrations were consistently higher compared to those of the related cord
      plasma samples (median: 13.0 microg/l vs. 7.3 microg/l). In the case of PFOA we
      observed only minor differences between PFOA concentrations within the analysed
      sample pairs (median: 2.6 microg/l vs. 3.4 microg/l for maternal and cord plasma
      samples, respectively). DISCUSSION: For both substances a crossing of the
      placental barrier could be shown. For PFOS we observed a decrease from maternal
      to cord plasma concentrations by a factor of 0.41-0.80. To the contrary, PFOA
      crosses the placental barrier obviously unhindered. These findings show that
      neonates are exposed to PFOS and PFOA via their mothers' blood. Given the current
      situation that only little is known about the consequences of PFOS and PFOA
      exposure in the early state of development of humans and the fact that in animal
      studies both substances showed developmental toxic effects further research
      regarding human health effects is indispensable.

PMID- 17219183
TI  - European dissemination of a web- and case-based learning system for occupational
      medicine: NetWoRM Europe.
AB  - OBJECTIVE: Occupation has a large impact on health in Europe. In order to prevent
      and recognize occupational diseases, medical students and physicians should know
      about the potentially causal relationship between profession and diseases as well
      as the basic legal aspects of occupational medicine (OM). However, the
      opportunity of bedside teaching, the students' most favoured way of teaching, is
      limited. METHODS: One possibility to complete and improve traditional training in
      OM is computer-oriented case-based learning. Using the authoring system "CASUS"
      (INSTRUCT AG) cases can be created and handled without knowledge in computer
      sciences. RESULTS: So far, 19 cases have been created and evaluated by students
      of German universities. Due to the great efforts arising from the creation of
      such multimedia cases it is desirable and cost-effective to use the existing
      cases at several medical universities. Therefore, the Net-based Training in Work
      Related Medicine (NetWoRM) project shares cases on an international base. In
      February and April 2005, 13 case-authors from 12 centres were trained in the
      basics of case creation during a 3 week programme in Munich. The overall
      evaluation of the participants indicated that this way of teaching case creation
      is very efficient. Up to now, nine cases were translated into English and five
      into Spanish. First implementation of the cases in Spain and Finland showed a
      good acceptance by the students but more evaluation has still to be done.
      CONCLUSION: Based on these results we conclude that exchange of case-based e
      learning in OM is feasible and rewarding on an international base.

PMID- 17219184
TI  - Familial steroid-sensitive nephrotic syndrome in Southern Israel: clinical and
      genetic observations.
AB  - Reports on genetically informative steroid-responsive (sensitive) idiopathic
      nephrotic syndrome (SSNS) families are lacking. We studied an extended SSNS
      Bedouin (B) family with a high rate of consanguinity. The clinical presentation
      and steroid response of its 11 affected individuals were similar to those of
      sporadic SSNS (spontaneous remission towards puberty and minimal change disease
      by kidney biopsy). Genome-wide linkage analysis, using a 382 microsatellite
      markers mapping set and additional markers adjacent to 80 candidate genes of the
      index family, did not support linkage to any chromosomal locus. Retrospective
      analysis of all additional children with SSNS treated by our institution in the
      past 20 years (n=96, 50% of them of Jewish origin) revealed another five non
      related B families with 2-3 first-degree cousins affected with SSNS in each. The
      overall familial SSNS rate among the B population (excluding the index family)
      was 28%, compared with 4% among Jews (Js) (OR 1.8-64, P<0.005). There were more
      Bs with simple SSNS than there were Js (71% and 40%, respectively; OR 3.58, 95%
      CI 1.41-9.23, P<0.01). In summary, SSNS in this index family was not linked to
      any of the presently known chromosomal loci nor predicted to be caused by
      mutation in any one of a list of genes associated with nephrotic syndrome (NS).
      The presence of other B families affected by SSNS supports the role for
      susceptibility genes enrichment, exposing highly consanguineous populations to an
      increased incidence of SSNS.

PMID- 17219185
TI  - Metabolic processes and carbon nutrient exchanges between host and pathogen
      sustain the disease development during sunflower infection by Sclerotinia
      sclerotiorum.
AB  - Interactions between the necrotrophic fungus Sclerotinia sclerotiorum and one of
      its hosts, Helianthus annuus L., were analyzed during fungal colonization of
      plant tissues. Metabolomic analysis, based on (13)C- and (31)P-NMR spectroscopy,
      was used to draw up the profiles of soluble metabolites of the two partners
      before interaction, and to trace the fate of metabolites specific of each partner
      during colonization. In sunflower cotyledons, the main soluble carbohydrates were
      glucose, fructose, sucrose and glutamate. In S. sclerotiorum extracts, glucose,
      trehalose and mannitol were the predominant soluble carbon stores. During
      infection, a decline in sugars and amino acids was observed in the plant and
      fungus total content. Sucrose and fructose, initially present almost exclusively
      in plant, were reduced by 85%. We used a biochemical approach to correlate the
      disappearance of sucrose with the expression and the activity of fungal
      invertase. The expression of two hexose transporters, Sshxt1 and Sshxt2, was
      enhanced during infection. A database search for hexose transporters homologues
      in the S. sclerotiorum genome revealed a multigenic sugar transport system.
      Furthermore, the composition of the pool of reserve sugars and polyols during
      infection was investigated. Whereas mannitol was produced in vitro and
      accumulated in planta, glycerol was exclusively produced in infected tissues and
      increased during colonization. The hypothesis that the induction of glycerol
      synthesis in S. sclerotiorum exerts a positive effect on osmotic protection of
      fungal cells and favors fungal growth in plant tissues is discussed. Taken
      together, our data revealed the importance of carbon-nutrient exchanges during
      the necrotrophic pathogenesis of S. sclerotiorum.

PMID- 17219186
TI  - [Coagulopathy in multiple trauma: new aspects of therapy].
AB  - Coagulopathy after trauma is a major cause for uncontrolled hemorrhage in trauma
      victims. Approximately 40% of trauma related deaths are attributed to or caused
      by exsanguination. Therefore the prevention of coagulopathy is regarded as the
      leading cause of avoidable death in these patients. Massive hemorrhage after
      trauma is usually caused by a combination of surgical and coagulopathic bleeding.
      Coagulopathic bleeding is multifactorial, including dilution and consumption of
      both platelets and coagulation factors, as well as dysfunction of the coagulation
      system. Because of the high mortality associated with hypothermia, acidosis and
      progressive coagulopathy, this vicious circle is often referred to as the lethal
      triad, potentially leading to exsanguination. To overcome this coagulopahty
      related bleeding an empiric therapy is often instituted by replacing blood
      components. However, the use of transfusion of red blood cells has been shown to
      be associated with post-injury infection and multiple organ failure. In the
      management of mass bleeding it is therefore crucial to have a clear strategy to
      prevent coagulopathy and to minimize the need for blood transfusion.

PMID- 17219187
TI  - [Septic shock due to vancomycin-resistant enterococci infection. Tigecycline
      monotherapy].
AB  - Adequate antimicrobial therapy is of crucial importance for the survival of
      critically ill patients with severe nosocomial infections. Tigecycline is an
      important therapeutic option for the treatment of infections caused by multi
      resistant Gram-positive and Gram-negative bacteria including vancomycin-resistant
      enterococci (VRE). A large randomised study (patients with APACHE-II-score >30
      excluded/mean APACHE-II-score 6) demonstrated that tigecycline is not inferior to
      imipenem/cilastatin for treatment of complicated intra-abdominal infections.
      However, no case has been reported with microbiological eradication and clinical
      cure in a patient with septic shock due to peritonitis caused by VRE and
      treatment with tigecycline monotherapy. Clinical details of a patient suffering
      from postoperative peritonitis are presented. The patient developed severe septic
      shock after pancreatic surgery (multiple organ failure, APACHE-II-score 34). As
      the site of anastomotic leakage was very small and could not be exactly
      identified, irrigation-suction drains were placed followed by closed
      postoperative continuous lavage. The pathogen responsible was identified as a
      vancomycin-resistant Enterococcus faecium, therefore monotherapy with tigecycline
      was started which resulted in microbiological response and clinical cure.
      Tigecycline is a new therapeutic option for the treatment of intra-abdominal
      infections and from an economic point of view financially rewarding when used as
      monotherapy.

PMID- 17219188
TI  - [The influence of transportation mode on mortality in polytraumatized patients.
      An analysis based on the German Trauma Registry].
AB  - BACKGROUND: Thirty years after its introduction in Germany, the benefits of the
      helicopter emergency medical service (HEMS) compared to ground ambulances (GA)
      still remain unclear. The aim of this study was to evaluate the influence of
      helicopter transport on rescue time and mortality based on the data of the German
      Trauma Registry. METHODS: Data from patients with multiple injuries were
      documented prospectively between 1993 and 2003 in different trauma centers in
      Germany, Switzerland, Austria and The Netherlands. From these data, patients with
      an injury severity score (ISS)<16 were excluded. Patients who were transported to
      the hospital without a physician were also excluded. The data from included
      patients were evaluated for time to hospital and influence of transportation
      service on mortality. RESULTS: A total of 7,534 patients with multiple injuries
      were included. Of these, 3,870 patients were transported by HEMS and 3,664
      reached the hospital by GA. There were 74.9% male patients in the HEMS group, and
      71.3% male patients in the GA group. The mean ISS was higher in the HEMS group
      (31.4 vs 30.7; P<0.01); patients transported by GA were older (HEMS: 39.2;
      NEF:41.3; P<0.01). The GA arrived on the scene after 14.33 min, the HEMS after
      18.18 min (P<0.01). Time at the scene was longer in the HEMS group (HEMS: 26:26
      min; NEF: 22:29 min; P<0.01). Intubation rate in the HEMS group was about 80%,
      while patients transported by GA were intubated in 60% of cases. The overall
      mortality was 30.9%. Evaluation of the TRISS prediction of survival showed a
      benefit for patients transported with HEMS. In a multivariate analysis, intubated
      patients with ISS<or=60 had a lower mortality rate if transported with HEMS (NEF:
      40.1%; HEMS 34.9%; P<0.01). CONCLUSIONS: Only minor differences in age and ISS
      were found between the groups. The time between the accident and arrival of the
      physician was longer in the HEMS group. The HEMS group also remained on the scene
      for longer, but had a higher rate of intervention. According to our analysis of
      the German Trauma Registry, patients with multiple injuries benefit from HEMS
      transportation.

PMID- 17219189
TI  - [The use of bisphosphonates in arthroplasty].
AB  - The use of bisphosphonates in joint arthroplasty is the latest field of
      application for these agents. The mechanism of action of bisphosphonates suggests
      that they may optimize long-term survival of the implant. Most important is their
      potency in suppressing periprosthetic osteolysis due to the inflammatory foreign
      body reaction of wear debris, to decrease periprosthetic osteopenia caused by
      stress-shielding and to improve the osseointegration of cementless metal
      implants. The present review provides the latest information on definite and
      presumed mechanisms of action of bisphosphonates and their clinical importance.

PMID- 17219190
TI  - Purification and characterization of two sugarcane bagasse-absorbable
      thermophilic xylanases from the mesophilic Cellulomonas flavigena.
AB  - We report the purification and characterization of two thermophilic xylanases
      from the mesophilic bacteria Cellulomonas flavigena grown on sugarcane bagasse
      (SCB) as the only carbon source. Extracellular xylanase activity produced by C.
      flavigena was found both free in the culture supernatant and associated with
      residual SCB. To identify some of the molecules responsible for the xylanase
      activity in the substrate-bound fraction, residual SCB was treated with 3 M
      guanidine hydrochloride and then with 6 M urea. Further analysis of the eluted
      material led to the identification of two xylanases Xyl36 (36 kDa) and Xyl53 (53
      kDa). The pI for Xyl36 was 5.0, while the pI for Xyl53 was 4.5. Xyl36 had a Km
      value of 1.95 mg/ml, while Xyl53 had a Km value of 0.78 mg/ml. In addition to
      SCB, Xyl36 and Xyl53 were also able to bind to insoluble oat spelt xylan and
      Avicel, as shown by substrate-binding assays. Xyl36 and Xyl53 showed optimal
      activity at pH 6.5, and at optimal temperature 65 and 55 degrees C, respectively.
      Xyl36 and Xyl53 retained 24 and 35%, respectively, of their original activity
      after 8 h of incubation at their optimal temperature. As far as we know, this is
      the first study on the thermostability properties of purified xylanases from
      microorganisms belonging to the genus Cellulomonas.

PMID- 17219191
TI  - Temperature sensing across species.
AB  - The ability to detect changes in temperature is a fundamental sensory mechanism
      for every species and provides organisms with a detailed view of the environment.
      This review focuses on what is known of the neuronal and molecular substrates for
      thermosensation across species, focusing on the three robust model systems
      extensively used to study sensory signaling, the nematode Caenorhabditis elegans,
      the fruit fly Drosophila melanogaster, and the laboratory mouse. Nematodes
      migrate to thermal climes that are amenable to their survival, a behavior that is
      regulated primarily through a single sensory neuron. Additionally, nematodes
      "learn" to seek out this temperate zone based upon their prior experience, a
      robust model of learning and memory. Drosophila larvae also prefer select thermal
      zones that are optimal for growth and have also developed vigorous mechanisms to
      avoid unfavorable conditions. In mammals, the transduction mechanisms for
      thermosensation have been identified primarily due to the fact that naturally
      occurring plant products evoke distinct psychophysical sensation of temperature
      change. More remarkably, the elucidation of the molecular sensors in mammals,
      along with those in Drosophila, has demonstrated conservation in the molecular
      mediators of temperature sensation across diverse species.

PMID- 17219192
TI  - The effect of shear stress on the basolateral membrane potential of proximal
      convoluted tubule of the rat kidney.
AB  - As consequence of glomerular filtration the viscosity of blood flowing through
      the efferent arteriole increases. Recently, we found that shear stress modulates
      proximal bicarbonate reabsorption and nitric oxide (NO.) was the chemical
      mediator of this effect. In the present work, we found that agonists of NO.
      production affected basolateral membrane potential (V (blm)) of the proximal
      convoluted tubule (PCT) epithelium. Using paired micropuncture experiments, we
      perfused peritubular capillaries with solutions with different viscosity while
      registering the V (blm). Our results showed that a 50% increment in the
      viscosity, or the addition of bradykinin (10(-5) M) to the peritubular perfusion
      solution, induced a significant and similar hyperpolarization of the V (blm) at
      the PCT epithelium of 6 +/- 0.7 mV (p < 0.05). Both hyperpolarizations were
      reverted by L-NAME (10(-4) M). Addition of 2,2'-(hydroxynitrosohydrazino) bis
      ethanamine (NOC-18) 3 x 10(-4) M to the peritubular perfusion solution induced a
      hyperpolarization of the same magnitude of that high viscosity or bradykinin.
      These results strongly suggest the involvement of NO. in the effect of high
      viscosity solutions. This effect seems to be mediated by activation of K+(ATP)
      channels as glybenclamide (5 x 10(-5) M) added to peritubular solutions induced a
      larger depolarization of the V (blm) with high viscosity solutions. Acetazolamide
      (5 x 10(-5) M) added to high viscosity solutions induced a larger
      hyperpolarization (8 +/- 1 mV; p < 0.05), suggesting that depolarizing current
      due to HCO(-)3 exit across the basolateral membrane damps the hyperpolarizing
      effect of high viscosity. Considering that Na(+) and consequently water
      reabsorption is highly dependent on electrical gradient, the present data suggest
      that the endothelium of kidney vascular bed interacts in paracrine fashion with
      the epithelia, affecting V (blm) and thus modulating PCT reabsorption.

PMID- 17219193
TI  - Ubiquitinated pathological lesions in frontotemporal lobar degeneration contain
      the TAR DNA-binding protein, TDP-43.
AB  - We have investigated the extent and pattern of immunostaining for the TAR DNA
      binding protein, TDP-43, in 37 patients with frontotemporal lobar degeneration
      with ubiquitin (UBQ) pathology (FTLD-U). We confirm that TDP-43 protein is a
      component of the UBQ immunoreactive (UBQ-ir) neuronal cytoplasmic inclusions
      (NCI), neuronal intranuclear inclusions (NII) and neurites of the cerebral cortex
      and hippocampus in FTLD-U. We further show that the same three histological
      patterns, previously identified by us according to the form, number and
      distribution of the UBQ-ir NCI, NII and neurites are equivalently present in TDP
      43 immunohistochemistry. TDP-43 immunoreactive (TDP-43-ir) NCI with rounded,
      spicular or skein-type appearance were seen in motor neurones of the trigeminal
      or facial cranial nerve nuclei in one patient with frontotemporal dementia (FTD)
      and in the spinal cord in three patients with FTD + motor neurone disease (MND).
      In patients with MND alone, TDP-43-ir NCI are common in anterior horn cells of
      the spinal cord, and occasionally seen in neurones of the hypoglossus nucleus. We
      show that TDP-43-ir NCI are also present within neurones in the superior and
      inferior olives in FTLD-U, and in some patients with MND. Although TDP-43 is
      normally seen as a nuclear protein, nuclear TDP-ir was not observed in neurones
      of the cerebral cortex, brainstem and spinal cord in FTLD-U or MND when NCI were
      present. We conclude that the UBQ-ir lesions of FTLD and MND are defined by the
      presence of TDP-43, and that these disorders can be subsumed into a single
      disease entity under the umbrella of TDP-43 proteinopathy.

PMID- 17219195
TI  - Gender disparity in radial and femoral arterial size: an ultrasound study.

PMID- 17219196
TI  - Inhaled nitric oxide increases endothelial permeability in Pseudomonas aeruginosa
      pneumonia.
AB  - OBJECTIVE: Pneumonia is a frequent cause of acute respiratory distress syndrome
      (ARDS), and Pseudomonas aeruginosa is a leading pathogen in nosocomial pneumonia.
      The management of ARDS remains a major problem, and only a limited number of
      options can improve the oxygenation. Inhaled nitric oxide (iNO) has been widely
      used, although this molecule is a free radical potentially harmful through the
      generation of toxic radical derivatives. The goal of our study was to assess the
      consequences of iNO (10 ppm) in a rat model of P. aeruginosa-induced lung injury.
      DESIGN: The animals were exposed for 24 h to iNO after instillation of the
      pathogen. Distal alveolar fluid clearance (DAFC) and epithelial and endothelial
      permeability were measured with a double flux of radio-labeled albumin. RESULTS:
      DAFC and epithelial permeability were increased in pneumonia but not influenced
      by iNO. In contrast, endothelial permeability was statistically significantly
      higher in the pneumonic animals exposed to iNO than in the pneumonic group
      without iNO (0.24+/-0.03 vs 0.47+/-0.1, p<0.05). This increase was not related to
      the production of nitrate/nitrite, nor to the increase of the inflammatory
      response evaluated by cytokine levels in the bronchoalveolar lavage fluid (TNF
      alpha, IL-6, IL-10). The alveolar recruitment of polymorphonuclear neutrophils
      was comparable in the pneumonic group exposed to iNO and the pneumonic group
      without iNO. CONCLUSION: iNO increases the endothelial permeability in P.
      aeruginosa pneumonia. The mechanism is not related to the production of
      nitrate/nitrite or to a greater inflammatory response.

PMID- 17219198
TI  - Increased induction of antitumor response by exosomes derived from interleukin-2
      gene-modified tumor cells.
AB  - PURPOSE: Tumor-derived exosomes (TEX) have been proposed as a new kind of cancer
      vaccine; however, their in vivo antitumor effects are not satisfactory. In order
      to further improve the efficacy of vaccination with TEX, we investigated whether
      interleukin-2 (IL-2) genetic modification of tumor cells can make IL-2 presence
      in the exosomes, thus increasing antitumor effects of the TEX. METHODS: E.G7-OVA
      tumor cells expressing Ovalbumin (OVA) as a tumor model antigen were used to
      prepare TEX by serial centrifugation and sucrose gradients ultracentrifugation.
      To demonstrate their antitumor effects, IL-2-containing exosomes (Exo/IL-2) were
      injected subcutaneously into C57BL/C mice: either bearing tumor or followed by
      tumor inoculation. RESULTS: We found IL-2 within those exosomes as detected by
      both ELISA and Western blot. Vaccination with these Exo/IL-2 could induce antigen
      specific Th1-polarized immune response and Cytotoxic T lymphocytes (CTL) more
      efficiently, resulting in more significant inhibition of tumor growth. CD8(+) T
      cells are the main effector cells, however, CD4(+) T cells, and NK cells are also
      involved in the induction of antitumor response of this approach. CONCLUSIONS:
      Our results demonstrate that IL-2 genetic modification of tumor cells can make
      the TEX contain IL-2 with the increased antitumor effects, representing a
      promising way of exosome-based tumor vaccine.

PMID- 17219197
TI  - Clinical significance of aromatase protein expression in axillary node negative
      breast cancer.
AB  - PURPOSE: Aromatase catalyzes the conversion of androgens to estrogens; its high
      expression in breast cancers may be responsible for the local high levels of
      estrogen and may promote tumor growth and progression; however, the clinical
      importance of aromatase remains unclear and needs to be further researched.
      METHODS: By immunochemistry, we detected aromatase, MMP2 and MMP9
      immunoreactivity in 244 axillary lymph node negative breast cancers. RESULTS:
      Aromatase immunoreactivity was positively associated with co-expression of MMP2
      and MMP9 (MMP2/9) in the estrogen receptor and/or progestin receptor- (ER/PR)
      positive patients (P < 0.05), but not in the ER and PR negative patients (P >
      0.05); aromatase status positively associated with tumor size in the
      postmenopausal patients (P < 0.05) but not in the premenopausal patients (P >
      0.05). The proportional hazards assumption was violated for aromatase status
      (global test, P < 0.05), and aromatase was an unfavorable prognostic factor for
      disease-free survival (DFS) (P = 0.04) in multivariate analysis of time-dependent
      non-proportional Cox regression. In the ER/PR-positive patients, positive
      aromatase staining was significantly associated with decreased overall survival
      (OS) (P = 0.04), but there was no such association in the ER and PR negative
      patients (P > 0.05). CONCLUSIONS: Our study suggested that local estrogen
      production by aromatase plays important roles in the growth and invasiveness of
      breast cancer; tumor aromatase status may be indicative of breast cancer
      prognosis in some patients.

PMID- 17219199
TI  - A glycoproteome database of normal human liver tissue.
AB  - PURPOSE: To extensively investigate the glycoproteins of normal human liver
      tissue, constructing the glycoprotein profile and database of the normal human
      liver tissue. METHODS: The total proteins were extracted from the normal human
      liver tissue and then subjected to two-dimensional electrophoresis (2-DE).
      Finally, 2-DE gels were stained according to the methods of multiplexed
      proteomics (MP) technology. Glycoprotein spots were excised from 2-DE gel and
      then characterized by matrix assisted laser desorption/ionization-time of flight
      mass spectrometry (MALDI-TOF-MS). RESULTS: The PDQuest software detected 1,011
      glycoprotein spots and 1,923 total protein spots in the 2-DE gels of sample from
      the normal human liver tissue. Furthermore, 116 species of glycoproteins were
      successfully identified via peptide mass profiling using MALDI-TOF-MS/MS and
      annotated to our databases. In addition, we also applied bioinformatics softwares
      to predict N- or O-glycosylation sites of identified glycoproteins. CONCLUSION:
      This study demonstrates the feasibility of a novel technological platform to
      contruct glycoprotein databases. These results lay the foundation for future
      physiological and pathological studies of the human liver.

PMID- 17219200
TI  - MYH mutations are rare in prostate cancer.
AB  - PURPOSE: Oxidative stress is considered a risk factor for prostate cancer
      development and is associated with the production of reactive oxygen species
      (ROS). The base excision repair gene MYH protects against ROS-mediated damage to
      DNA. Inherited MYH mutations predispose to colorectal adenomas and cancer. A
      compromised base-excision repair function due to defective MYH may contribute to
      prostate carcinogenesis. Here, we examine the genetic contribution of MYH to
      prostate cancer risk. METHODS: Patients diagnosed with high-grade prostatic
      intraepithelial neoplasia (HGPIN) alone (n = 45), prostate cancer alone (n = 123)
      or both (n = 82) were screened for the two most common mutations in the MYH gene
      using PCR-based RFLP analysis. A single patient with an inherited MYH mutation as
      well as a subset of 26 patients presenting with a family history of colorectal
      cancer were screened for additional MYH mutations by direct sequencing of the
      entire coding region. RESULTS: Biallelic germline mutations in MYH were not
      detected among prostate cancer patients. Only a single patient was a heterozygous
      carrier for the Y165C missense mutation. Allelic deletion or somatic mutation of
      the remaining MYH allele was not identified in this patient's tumor DNA. Two
      patients harbored V22M polymorphism and three patients were carriers of Q324H
      polymorphism. CONCLUSIONS: MYH mutations are unlikely to contribute to prostate
      cancer risk.

PMID- 17219201
TI  - Molecular genetic defects in endometrial carcinomas: microsatellite instability,
      PTEN and beta-catenin (CTNNB1) genes mutations.
AB  - PURPOSE: The present study aims to assess the incidence of microsatellite
      instability (MSI) and mutations in the PTEN and beta-catenin (CTNNB1) genes in
      endometrial carcinomas and to analyze the detected defects in these factors in
      relation to each other and to the clinico-pathological features of tumors.
      MATERIALS AND METHODS: In a series of 56 endometrioid endometrial carcinomas, the
      status of MSI was determined using nine polymorphic markers, and mutations in all
      exons of the PTEN gene and in exon 3 of the CTNNB1 gene were evaluated by SSCP
      and sequencing methods. RESULTS: Microsatellite instability was found in 18
      carcinomas (32.1%, MSI+); the remaining 38 tumors were microsatellite stable (MSI
      ). In 15 cases (26.8%), a loss of heterozygosity (LOH) at the studied
      microsatellite markers also occurred. In 29 carcinomas (51.8%), mutations were
      found in the PTEN gene and in nine tumors (16.1%) in the CTNNB1 gene. PTEN
      mutations occurred significantly more frequently in MSI+ than in MSI- tumors
      (77.8 vs. 39.5%, p = 0.007), but, except for one, none of them was attributable
      to MSI. In contrast, incidence of CTNNB1 mutations in MSI+ and MSI- tumors no
      significantly differed between themselves (16.7 vs. 15.8%, p = 0.760).
      Interestingly, mutations in the CTNNB1 gene most frequently coexisted with
      mutations in the PTEN gene (7/9, 77.8%). However, this finding requires future
      verification on a larger group of cases. The incidence of MSI and PTEN, but not
      CTNNB1 mutations, was significantly more common in poorly, than in well-to
      moderately, differentiated tumors (G3 vs. G1 + G2; p = 0.042, 0.039 and 0.958,
      respectively). CONCLUSION: We conclude that most frequently occurring mutations
      in the PTEN gene may be a key event for the tumorigenesis of endometrioid
      endometrial carcinomas, while coexistence or absence of microsatellite
      instability or mutations in the CTNNB1 gene may reflect the heterogeneity of
      molecular mechanisms contributing to the development of these tumors.

PMID- 17219202
TI  - Effect of lycopene on insulin-like growth factor-I, IGF binding protein-3 and IGF
      type-I receptor in prostate cancer cells.
AB  - PURPOSE: Prostate cancer is the second most common cancer that leads to death in
      elderly men. The risk of prostate cancer prevalence is often associated with the
      elevated level of insulin-like growth factor-I (IGF-I) and decreased level of IGF
      binding protein 3 (IGFBP-3). Lycopene, a carotenoid, reduces the proliferation of
      cancer cells and induces apoptosis. Hence, higher intake of lycopene can be
      associated with the lower risk of prostate cancer. However, the mechanism of
      action of lycopene in the prevention of prostate cancer is still unclear. The
      present study was carried out to study the effects of lycopene on the components
      of IGF system and apoptosis in androgen-independent prostate cancer cells (PC-3
      cells). METHODS: PC-3 cells were treated with various concentrations of lycopene,
      (20, 40 and 60 microM) for 24, 48, 72 and 96 h. IGF-I, IGFBP-3 and IGF-I receptor
      (IGF-IR) levels in lycopene-treated cells were evaluated. Annexin V and propidium
      iodide (PI) binding studies were done to assess apoptosis. RESULTS: PC-3 cells
      treated with lycopene showed a significant decrease in cell proliferation.
      Lycopene, at a dose of 40 microM, significantly increased the level of IGFBP-3.
      Lycopene-induced apoptosis was confirmed by annexin V and PI binding. Lycopene
      induced DNA fragmentation was absent after 24 h treatment whereas the same was
      observed after 48 h treatment. There was a significant decrease in the IGF-IR
      expression after the cells were treated with lycopene and IGF-I. CONCLUSION: The
      data obtained suggest that the components of the IGF system may act as a positive
      regulator of lycopene-induced apoptosis in PC-3 cells. Thus, the observed
      lycopene-induced biological effects and their associated mechanisms are
      encouraging and may lead to the development of a highly successful drug for the
      treatment of prostate cancer.

PMID- 17219203
TI  - Molecular characterization of the canine mitochondrial DNA control region for
      forensic applications.
AB  - The canine mitochondrial DNA (mtDNA) control region of 133 dogs living in the
      area around Innsbruck, Austria was sequenced. A total of 40 polymorphic sites
      were observed in the first hypervariable segment and 15 in the second, which
      resulted in the differentiation of 40 distinct haplotypes. We observed five
      nucleotide positions that were highly polymorphic within different haplogroups,
      and they represent good candidates for mtDNA screening. We found five point
      heteroplasmic positions; all located in HVS-I and a polythymine region in HVS-II,
      the latter often being associated with length heteroplasmy. In contrast to human
      mtDNA, the canine control region contains a hypervariable 10 nucleotide repeat
      region, which is located between the two hypervariable regions. In our population
      sample, we observed eight different repeat types, which we characterized by
      direct sequencing and fragment length analysis. The discrimination power of the
      canine mtDNA control region was 0.93, not taking the polymorphic repeat region
      into consideration.

PMID- 17219204
TI  - Quantitative trait loci and candidate gene mapping of aluminum tolerance in
      diploid alfalfa.
AB  - Aluminum (Al) toxicity in acid soils is a major limitation to the production of
      alfalfa (Medicago sativa subsp. sativa L.) in the USA. Developing Al-tolerant
      alfalfa cultivars is one approach to overcome this constraint. Accessions of wild
      diploid alfalfa (M. sativa subsp. coerulea) have been found to be a source of
      useful genes for Al tolerance. Previously, two genomic regions associated with Al
      tolerance were identified in this diploid species using restriction fragment
      length polymorphism (RFLP) markers and single marker analysis. This study was
      conducted to identify additional Al-tolerance quantitative trait loci (QTLs); to
      identify simple sequence repeat (SSR) markers that flank the previously
      identified QTLs; to map candidate genes associated with Al tolerance from other
      plant species; and to test for co-localization with mapped QTLs. A genetic
      linkage map was constructed using EST-SSR markers in a population of 130
      BC(1)F(1) plants derived from the cross between Al-sensitive and Al-tolerant
      genotypes. Three putative QTLs on linkage groups LG I, LG II and LG III,
      explaining 38, 16 and 27% of the phenotypic variation, respectively, were
      identified. Six candidate gene markers designed from Medicago truncatula ESTs
      that showed homology to known Al-tolerance genes identified in other plant
      species were placed on the QTL map. A marker designed from a candidate gene
      involved in malic acid release mapped near a marginally significant QTL (LOD
      2.83) on LG I. The SSR markers flanking these QTLs will be useful for
      transferring them to cultivated alfalfa via marker-assisted selection and for
      pyramiding Al tolerance QTLs.

PMID- 17219205
TI  - BARCSoySNP23: a panel of 23 selected SNPs for soybean cultivar identification.
AB  - This report describes a set of 23 informative SNPs (BARCSoySNP23) distributed on
      19 of the 20 soybean linkage groups that can be used for soybean cultivar
      identification. Selection of the SNPs to include in this set was made based upon
      the information provided by each SNP for distinguishing a diverse set of soybean
      genotypes as well as the linkage map position of each SNP. The genotypes included
      the ancestors of North American cultivars, modern North American cultivars and a
      group of Korean cultivars. The procedure used to identify this subset of highly
      informative SNP markers resulted in a significant increase in the power of
      identification versus any other randomly selected set of equal number. This
      conclusion was supported by a simulation which indicated that the 23-SNP panel
      can uniquely distinguish 2,200 soybean cultivars, whereas sets of randomly
      selected 23-SNP panels allowed the unique identification of only about 50
      cultivars. The 23-SNP panel can efficiently distinguish each of the genotypes
      within four maturity group sets of additional cultivars/lines that have identical
      classical pigmentation and morphological traits. Comparatively, the 13
      trinucleotide SSR set published earlier (BARCSoySSR13) has more power on a per
      locus basis because of the multi-allelic nature of SSRs. However, the assay of bi
      allelic SNP loci can be multi-plexed using non-gel based techniques allowing for
      rapid determination of the SNP alleles present in soybean genotypes, thereby
      compensating for their relatively low information content. Both BARCSoySNP23 and
      BARCSoySSR13 were highly congruent relative to identifying genotypes and for
      estimating population genetic differences.

PMID- 17219206
TI  - Molecular mapping of resistance genes to tan spot [Pyrenophora tritici-repentis
      race 1] in synthetic wheat lines.
AB  - Synthetic wheat lines (2n = 6x = 42, AABBDD), which are amphiploids developed
      from the hybrid between tetraploid wheat (Triticum turgidum L., 2n = 4x = 28,
      AABB) and Aegilops tauschii Coss. (2n = 2x = 14, DD), are important sources of
      resistance against tan spot of wheat caused by Pyrenophora tritici-repentis. In
      the present study, inheritance, allelism and genetic linkage analysis in
      synthetic wheat lines have been carried out. Segregation analysis of the
      phenotypic and molecular data in F(2:3) populations of CS/XX41, CS/XX45, and
      CS/XX110 has revealed a 1:2:1 segregation ratio indicating that resistance of tan
      spot in these synthetic lines is controlled by a single gene. Allelism tests
      detected no segregation for susceptibility among F(1) and F(2) plants derived
      from intercrosses of the resistance lines XX41, XX45 and XX110 indicating that
      the genes are either allelic or tightly linked. Linkage analysis using SSR
      markers showed that all the three genes: tsn3a in XX41, Tsn3b in XX45 and tsn3c
      in XX110 are clustered in the region around Xgwm2a, located on the short arm of
      chromosome 3D. The linked markers and genetic relationship of these genes will
      greatly facilitate their use in wheat breeding and deployment of cultivars
      resistant to tan spot.

PMID- 17219207
TI  - Analysis of an introgressed Nicotiana tomentosa genomic region affecting leaf
      number and correlated traits in Nicotiana tabacum.
AB  - Germplasm from closely related diploid relatives of tobacco (Nicotiana tabacum
      L.) could be of value for continued genetic modification of this species and for
      mapping quantitative trait loci (QTLs). We examined near isogenic tobacco lines
      and hybrids differing for an introgressed genomic region from N. tomentosa Ruiz
      and Pavon designated as Many Leaves that exhibits a large influence on leaf
      number and correlated traits. Within a 'Red Russian' genetic background, the
      region acted in an additive to partially dominant fashion to delay flowering
      time, and increase leaf number, plant height, and green leaf yield. Evidence of
      epistasis was observed as the region affected these traits to varying degrees in
      diverse near isogenic hybrids. Fifteen amplified fragment length polymorphism
      (AFLP) markers of N. tomentosa origin were mapped within a single linkage group
      of 34.5 cM using a population of 207 BC(1)F(1) individuals segregating for Many
      Leaves. Composite interval mapping produced 2-LOD confidence intervals for likely
      QTL positions influencing leaf number (3.1 cM region), plant height (2.9 cM
      region), and days to flowering (3.3 cM region). These intervals were overlapping.
      Results demonstrate that genomic regions with large genetic effects can be
      transferred to tobacco from closely related diploid relatives, and that
      sufficient recombination within these regions may permit mapping of genes
      controlling quantitative traits. Materials and results described here may be
      useful in future research to gain insight on the genetic control of the
      transition from vegetative to reproductive development in Nicotiana.

PMID- 17219208
TI  - A 1,000-loci transcript map of the barley genome: new anchoring points for
      integrative grass genomics.
AB  - An integrated barley transcript map (consensus map) comprising 1,032 expressed
      sequence tag (EST)-based markers (total 1,055 loci: 607 RFLP, 190 SSR, and 258
      SNP), and 200 anchor markers from previously published data, has been generated
      by mapping in three doubled haploid (DH) populations. Between 107 and 179 EST
      based markers were allocated to the seven individual barley linkage groups. The
      map covers 1118.3 cM with individual linkage groups ranging from 130 cM
      (chromosome 4H) to 199 cM (chromosome 3H), yielding an average marker interval
      distance of 0.9 cM. 475 EST-based markers showed a syntenic organisation to known
      colinear linkage groups of the rice genome, providing an extended insight into
      the status of barley/rice genome colinearity as well as ancient genome
      duplications predating the divergence of rice and barley. The presented barley
      transcript map is a valuable resource for targeted marker saturation and
      identification of candidate genes at agronomically important loci. It provides
      new anchor points for detailed studies in comparative grass genomics and will
      support future attempts towards the integration of genetic and physical mapping
      information.

PMID- 17219209
TI  - Generation and characterization of low phytic acid germplasm in rice (Oryza
      sativa L.).
AB  - Phytic acid (PA, myo-inositol 1,2,3,4,5,6-hexakisphosphate), or its salt form,
      phytate, is commonly regarded as the major anti-nutritional component in cereal
      and legume grains. Breeding of low phytic acid (lpa) crops has recently been
      considered as a potential way to increase nutritional quality of crop products.
      In this study, eight independent lpa rice mutant lines from both indica and
      japonica subspecies were developed through physical and chemical mutagenesis.
      Among them, five are non-lethal while the other three are homozygous lethal. None
      of the lethal lines could produce homozygous lpa plants through seed germination
      and growth under field conditions, but two of them could be rescued through in
      vitro culture of mature embryos. The non-lethal lpa mutants had lower PA content
      ranging from 34 to 64% that of their corresponding parent and four of them had an
      unchanged total P level. All the lpa mutations were inherited in a single
      recessive gene model and at least four lpa mutations were identified mutually non
      allelic, while the other two remain to be verified. One mutation was mapped on
      chromosome 2 between microsatellite locus RM3542 and RM482, falling in the same
      region as the previously mapped lpa1-1 locus did; another lpa mutation was mapped
      on chromosome 3, tightly linked to RM3199 with a genetic distance of 1.198 cM.
      The latter mutation was very likely to have happened to the LOC_Os03g52760, a
      homolog of the maize myo-inositol kinase (EC 2.7.1.64) gene. The present work
      greatly expands the number of loci that could influence the biosynthesis of PA in
      rice, making rice an excellent model system for research in this area.

PMID- 17219210
TI  - Large-scale DNA polymorphism study of Oryza sativa and O. rufipogon reveals the
      origin and divergence of Asian rice.
AB  - Polymorphism over approximately 26 kb of DNA sequence spanning 22 loci and one
      region distributed on chromosomes 1, 2, 3 and 4 was studied in 30 accessions of
      cultivated rice, Oryza sativa, and its wild relatives. Phylogenetic analysis
      using all the DNA sequences suggested that O. sativa ssp. indica and ssp.
      japonica were independently domesticated from a wild species O. rufipogon. O.
      sativa ssp. indica contained substantial genetic diversity (pi = 0.0024), whereas
      ssp. japonica exhibited extremely low nucleotide diversity (pi = 0.0001)
      suggesting the origin of the latter from a small number of founders. O. sativa
      ssp. japonica contained a larger number of derived and fixed non-synonymous
      substitutions as compared to ssp. indica. Nucleotide diversity and genealogical
      history substantially varied across the 22 loci. A locus, RLD15 on chromosome 2,
      showed a distinct genealogy with ssp. japonica sequences distantly separated from
      those of O. rufipogon and O. sativa ssp. indica. Linkage disequilibrium (LD) was
      analyzed in two different regions. LD in O. rufipogon decays within 5 kb, whereas
      it extends to approximately 50 kb in O. sativa ssp. indica.

PMID- 17219211
TI  - Synchronisation of tibial rotational alignment with femoral component in total
      knee arthroplasty.
AB  - The rotational axis of the tibial component in total knee arthroplasty described
      by Insall is generally accepted, but rotational mismatch between the femoral and
      the tibial components can occur because the alignment of each component is
      determined separately. We developed a connecting instrument to synchronise the
      axis of the tibia to the axis of the femur. We compared the rotational axis of
      the tibial component using our method and medial one third of tibial tuberosity
      (Insall's reference) in 70 consecutive TKAs. The rotational axis of the tibial
      component from the femoro-tibial synchronisation was rotated internally 13.8
      degrees +/- 5.8 degrees (range, 2 degrees - 24 degrees ) more than the axis of
      Insall's reference. Eighty three percent of patellae tracked centrally and the
      patellae tilt measured 2.2 degrees on average. More attention should be given to
      the rotational congruency between the femoro-tibial components, because the
      recent prosthetic design has more conforming articular surfaces.

PMID- 17219212
TI  - The treatment of transtrochanteric fractures of the femur with a minimally
      invasive technique using an extramedullary implant MINUS System.
AB  - We report here the results of a retrospective study on 120 patients treated for
      transtrochanteric fractures of the femur using a minimally invasive technique
      with an extramedullary sliding pin as implant - which we denoted the MINUS
      System. The evaluation was carried out in in the postoperative period, and the
      levels of haemoglobin (Hb) and haematocrit (Ht), surgical time, radiological
      screening time and pain levels were recorded. Prior to the operation, mean Hb and
      Ht were 11.69 g/dl and 35.72%, respectively; in the immediate postoperative
      period, they were 10.35 g/dl and 32.4%, respectively. Mean operating time was
      39.35 min. Average postoperative pain was assessed at 4.44 (on a scale of 1 to
      10). The average time for screening was 1.07 min. Based on these criteria, we
      conclude that the minimally invasive technique of the MINUS System allows for a
      shorter operating time and a minimal blood loss in the treatment of
      transtrochanteric fractures of the femur.

PMID- 17219213
TI  - Effect of surgical delay on outcome in hip fracture patients: a retrospective
      multivariate analysis of 192 patients.
AB  - Previous studies have not demonstrated consistent results on the effect of
      surgical delay on outcome. This study investigated the association between the
      delay to surgery and the development of postoperative complications, length of
      hospital stay (LOS) and one-year mortality. Patients that underwent surgery for a
      hip fracture in a two-year period were included in a retrospective study. Uni-
      and multivariate regression analysis was performed in 192 hip fracture patients.
      There was a trend towards fewer postoperative complications (P = 0.064;
      multivariate regression, MR) and shorter LOS (P = 0.088; MR) in patients with a
      delay of less than one day to surgery. No association between surgical delay and
      one-year mortality was found in the population as a whole (P = 0.632; univariate
      regression, UR). Delay to surgery beyond one day was associated with an increased
      risk of infectious complications (P = 0.004; MR). In ASA I and II class patients,
      operation beyond one day from admission was associated with an increased risk of
      one-year mortality (P = 0.03; MR) and more postoperative infectious complications
      (P = 0.02; MR). The trends towards fewer complications and shorter LOS suggest
      that early surgery (within one day from admission) is beneficial for hip fracture
      patients who are able to undergo an operation.

PMID- 17219214
TI  - Biological effects of the PINK1 c.1366C>T mutation: implications in Parkinson
      disease pathogenesis.
AB  - PINK1 gene mutations are a cause of recessively inherited, early-onset
      Parkinson's disease. In some patients, a single heterozygous mutation has been
      identified, including the recurrent c.1366C>T transition. The interpretation of
      this finding remains controversial. Furthermore, the c.1366C>T mutation is
      associated with lower levels of PINK1 transcript, raising the question of whether
      mRNA levels correlate with the clinical status. We sequenced genomic DNA and copy
      DNA (cDNA) from 20 subjects carrying the c.1366C>T mutation in the homozygous (n
      = 5) or heterozygous (n = 15) state. In 17 mutation carriers, messenger RNA
      (mRNA) was quantified by real-time PCR using four different assays (PINK1 exon 5
      6 or exon 7-8 relative to control genes SDHA or YWHAZ). Genomic sequencing
      confirmed the presence and zygosity of PINK1 mutations. cDNA sequencing in
      heterozygous mutation carriers revealed a strong wild-type and a much weaker or
      almost absent mutant signal, whereas in the homozygous patients, only the mutant
      signal was detected. Homozygous and heterozygous carriers showed PINK1 mRNA
      levels relative to a reference gene in the range of 0.1-0.2 and 0.5-0.6,
      respectively, compared with values of 0.9-1.0 in mutation-negative individuals.
      Treatment of lymphoblasts from a heterozygous mutation carrier with cycloheximide
      markedly increased the mutant transcript signal. We conclude that the recurrent
      PINK1 c.1366C>T mutation exerts a major effect at the mRNA level (80-90%
      reduction), most likely via nonsense-mediated mRNA decay. The absence of
      correlation between PINK1 mRNA levels and clinical status in heterozygous
      mutation carriers suggests that other genetic or environmental factors play a
      role in determining the phenotypic variability associated with the c.1366C>T
      mutation.

PMID- 17219215
TI  - Asymmetric localization of Notch2 on the microvillous surface in choroid plexus
      epithelial cells.
AB  - Notch family molecules are transmembrane receptors that play various roles in
      contact-dependent cell-cell interactions in a wide range of organs. In the brain,
      Notch2, but not the other members of Notch, is expressed in the choroid plexus at
      an exceptionally high level. We immunohistochemically examined the cellular and
      subcellular localization of Notch2 protein in the choroid plexus using confocal
      and electron microscopy. Unexpectedly, Notch2 was asymmetrically localized on the
      microvillous surface of epithelial cells in the choroid plexus of both postnatal
      and adult rats. This localization pattern of Notch2 suggests its novel and
      unknown role independent of contact with adjacent cells in the choroid plexus. In
      organotypic cultures of the choroid plexus, the addition of anti-Notch2 antibody
      resulted in deformation of microvilli in epithelial cells, which suggests a role
      of Notch2 in the maintenance of the microvillous structure in choroid plexus
      epithelial cells.

PMID- 17219216
TI  - Acute effects of nocturnal doses of MDMA on measures of impulsivity and
      psychomotor performance throughout the night.
AB  - INTRODUCTION: Previous studies on the acute effects of MDMA on psychomotor
      performance and impulsivity showed that MDMA acts as a stimulant. These studies
      assessed performance during daytime, whereas in real life, dance-attendees
      leaving a party use the drug during the night. OBJECTIVES: The present study
      aimed to assess the effects of nocturnal doses of MDMA on psychomotor performance
      and impulsivity during the night and after a night of sleep deprivation.
      MATERIALS AND METHODS: Fourteen healthy subjects participated in a double-blind,
      placebo-controlled, two-way within-subject study. The treatment was MDMA (75 and
      50 mg) divided over the evening or double placebo. Psychomotor and impulsivity
      tasks were conducted four times throughout the evening and night. A vigilance
      test was conducted once, at 5 A.M.,: and a sleepiness scale was presented to the
      subjects ten times throughout the evening and night. RESULTS: MDMA impaired
      tracking performance in a simple tracking task. Divided attention task
      performance was also impaired as indicated by a decrease in secondary task
      performance under the influence of MDMA compared with placebo. MDMA did not
      affect impulsivity measures. Vigilance performance decreased as a function of
      time on task, but this decrement was less during MDMA treatment compared to
      placebo. After the administration of MDMA, the sleepiness scale scores were lower
      during the night when compared with placebo. This difference between MDMA and
      placebo disappeared in the morning. CONCLUSION: It is concluded that nocturnal
      doses of MDMA may produce impairments of tracking performance and divided
      attention throughout the night that are additive to performance impairment
      produced by sleep loss.

PMID- 17219217
TI  - Cognitive, psychomotor and actual driving performance in healthy volunteers after
      immediate and extended release formulations of alprazolam 1 mg.
AB  - RATIONALE: Alprazolam extended-release (XR) is approved for the treatment of
      panic disorder. This sustained formulation is absorbed in a delayed manner and is
      therefore expected to produce fewer and less severe side effects than its
      immediate release equivalent (alprazolam IR). The effect of alprazolam XR on
      potentially dangerous daily activities, such as driving a car, is expected to be
      less as compared to alprazolam IR. OBJECTIVES: The present study was designed to
      compare the effects of alprazolam XR (1 mg) and alprazolam IR (1 mg) on actual
      driving ability and cognitive function. METHOD: Eighteen healthy volunteers (aged
      20-45 years) participated in a double-blind, placebo-controlled, three-way
      crossover study. At 4 h post-dose, subjects performed a standardized driving test
      on a primary highway in normal traffic. Cognitive and psychomotor tests were
      assessed 1, 2.5, and 5.5 h post-dose. Memory functioning was measured only 1 h
      after administration. RESULTS: Both formulations severely impaired driving
      performance between 4 and 5 h after administration. The magnitude of impairment
      in the driving test observed with alprazolam XR was about half that observed with
      alprazolam IR. Laboratory test results were in line with the driving data.
      CONCLUSIONS: The acute impairing effects of alprazolam XR 1 mg on driving and
      psychomotor functions were generally less, as compared to its immediate-release
      equivalent, but still of sufficient magnitude to increase the risk of becoming
      involved in traffic accidents.

PMID- 17219218
TI  - The supramammillo-septal-hippocampal pathway mediates sensorimotor gating
      impairment and hyperlocomotion induced by MK-801 and ketamine in rats.
AB  - RATIONALE: Ketamine or MK-801 induced sensorimotor gating deficit, but the
      underlying neural mechanisms are not completely known. We have previously
      demonstrated that the medial septum (MS) mediated the phencyclidine-induced
      deficit in prepulse inhibition of the acoustic startle (PPI) in rats. OBJECTIVES:
      We investigated the involvement of the supramammillary area (SUM) to MS pathway
      in PPI impairment and behavioral hyperlocomotion induced by MK-801 or ketamine in
      rats and correlated the behavioral deficits with hippocampal gamma wave increase.
      MATERIALS AND METHODS: Ketamine (6 mg/kg, s.c.) or MK-801 (0.5 mg/kg, i.p.) was
      administered after infusion of saline or the GABA(A) receptor agonist, muscimol
      (0.25 microg), into the MS or SUM. Locomotion, PPI, and hippocampal
      electroencephalogram (EEG) were recorded. RESULTS: MK-801 or ketamine induced PPI
      impairment and behavioral hyperlocomotion, accompanied by an increase in
      hippocampal gamma waves (30-100 Hz). The changes in behavior and gamma waves
      induced by ketamine or MK-801 were antagonized by pre-infusion of muscimol, but
      not saline, into the SUM or MS. Infusion of muscimol into the SUM alone did not
      significantly affect PPI, but it suppressed spontaneous locomotor behavior and
      hippocampal EEG. Infusion of ionotropic glutamate receptor antagonists into the
      MS did not affect the PPI deficit or the gamma wave increase after MK-801.
      CONCLUSIONS: A non-glutamatergic component of the supramammillo-septal pathway
      mediates the hyperlocomotion and the deficits in PPI induced by MK-801 or
      ketamine. Inactivation of the MS or SUM normalized both the hippocampal gamma
      waves and the behavioral deficits (PPI impairment and hyperlocomotion).

PMID- 17219219
TI  - Effects of acute and chronic antidepressant treatments on memory performance: a
      comparison between paroxetine and imipramine.
AB  - RATIONALE: The cognitive impairments apparent in many depressed patients appear
      to be alleviated by chronic treatments with antidepressants. However, evaluation
      of antidepressant treatments in rodents rarely includes investigation of their
      effects on cognitive performance. OBJECTIVES: The aim of this study was to
      investigate in rat the effects of paroxetine, a selective serotonin reuptake
      inhibitor antidepressant, and imipramine, a tricyclic antidepressant, on learning
      and memory in spatial and non-spatial tasks. MATERIALS AND METHODS: Adult male
      Sprague-Dawley rats weighing 230-250 g were used in two sets of experiments.
      RESULTS: Spatial working memory was first tested in a radial-arm maze using the
      delayed spatial win-shift task. During the course of a 10-day treatment,
      paroxetine-treated rats (10 mg/kg) did not show any deficit in memory
      performance. Conversely, imipramine-treated rats (10 mg/kg) made significantly
      more errors than controls. Secondly, we tested temporal order memory for objects.
      Rats received one injection or chronic injections (28 days) of imipramine (10
      mg/kg), paroxetine (10 mg/kg) or saline. In contrast to controls, on the day
      after the acute injection, both imipramine- and paroxetine-treated rats were
      unable to discriminate the old from the recent objects. After chronic treatment,
      the imipramine-treated rats were unable to differentiate between the two objects,
      whereas paroxetine-treated rats, as controls, spent more time exploring the old
      one. When the delay before the test phase was increased to 4 h, controls could
      not discriminate the objects, whereas rats treated for 28 days with paroxetine
      were able to distinguish the old from the recent object. CONCLUSIONS: In contrast
      to the persistent harmful effects of imipramine, chronic treatment with
      paroxetine does not alter spatial working memory performance and appears to
      improve temporal order memory performance.

PMID- 17219220
TI  - Hallucinatory and rewarding effect of salvinorin A in zebrafish: kappa-opioid and
      CB1-cannabinoid receptor involvement.
AB  - RATIONALE: The hallucinatory effect and potential abuse of salvinorin A, the
      major ingredient of Salvia divinorum, has not been documented in animals.
      OBJECTIVE: The effects of salvinorin A on the zebrafish (Danio rerio) model,
      through its swimming behavior and conditioned place preference (CPP) task, was
      studied. MATERIALS AND METHODS: Swimming activity was determined in a squared
      observational chamber after an i.m. treatment of salvinorin A (0.1-10 microg/kg).
      For the CPP test, zebrafish were given salvinorin A (0.2 and 1 microg/kg) or
      vehicle and evaluated in a two-compartment chamber. RESULTS: Salvinorin A (0.1
      and 0.2 microg/kg) induced accelerated swimming behavior in comparison with
      vehicle, whereas a "trance-like" effect, at doses as 5 and 10 microg/kg, was
      obtained. Pretreatment with the kappa-opioid antagonist, nor-binaltorphimine (nor
      BNI; 10 mg/kg) and the cannabinoid type 1 (CB(1)) antagonist, rimonabant (1
      mg/kg), blocked salvinorin A-induced both stimulating and depressive effects
      obtained at a dose of 0.2 and 10 microg/kg, respectively. In the CPP test,
      salvinorin A (0.2 and 0.5 microg/kg) produced an increase in the time spent in
      the drug-associated compartment. A dose of 1 microg/kg produced no effect,
      whereas a dose of 80 microg/kg induced aversion. Pretreatment with nor-BNI or
      rimonabant fully reversed the reinforcing properties of salvinorin A (0.5
      microg/kg). CONCLUSIONS: Taken together, these results indicate that salvinorin
      A, as is sometimes reported in humans, exhibits rewarding effects, independently
      from its motor activity, suggesting the usefulness of the zebrafish model to
      study addictive behavior. These effects appear mediated by activation of both
      kappa-opioid and cannabinoid CB(1) receptors.

PMID- 17219221
TI  - Immunocytochemistry of Psoroptes cuniculi stained by sera from naive and infested
      rabbits: preliminary results.
AB  - Immunocytochemistry was used to identify possible target antigens in the
      digestive system of Psoroptes cuniculi. Sera from three recently acutely infested
      rabbits, from rabbits with a mild long lasting infestation, and from a rabbit
      with repeated mite infestations and no longer able to maintain a population of P.
      cuniculi were used to determine any antibody specificity to the mite digestive
      system. The reactivity of these sera was compared with sera from three un
      infested animals. The different pool of sera targeted different mite antigens; in
      particular, sera from the resistant rabbit and the chronically infested rabbits
      reacted with gut cells, faecal material and cuticle, while sera from the recently
      infested rabbits reacted with gut contents, faecal material and cuticle of the
      parasites but not with gut cells. Finally, sera from un-infested rabbits did not
      demonstrate any specificity to P. cuniculi antigens reacting only with mite gut
      contents in a weak manner. These preliminary data suggest the presence of
      antibodies induced in the host blood by infection, which act against the parasite
      by binding to antigen at the surface of its gut.

PMID- 17219222
TI  - Crustacean fish parasites from Segara Anakan Lagoon, Java, Indonesia.
AB  - The present study is the first investigation on ectoparasites of commercial
      important fish from Segara Anakan, a brackish water lagoon located at the
      southern coast of Java, Indonesia. Eight economically important marine fish
      species (Mugil cephalus, Siganus javus, Scatophagus argus, Caranx sexfasciatus,
      Lutjanus johnii, Eleutheronema tetradactylum, Johnius coitor, and Epinephelus
      coioides) were examined for crustacean parasites. Prevalence and intensity data
      for each parasite species are given, together with an analysis of the origin and
      possible transmission pathways. A highly divers copepod fauna consisting of 23
      different species and two isopods was found. All fish species were at least
      infested with two copepod species, with the exception of L. johnii, S. argus, and
      M. cephalus. With seven and six species, respectively, they harboured the most
      species-rich ectoparasite fauna. The copepods Ergasilus sp. 3 and Caligus
      acanthopagri on S. argus showed the highest prevalence (78.6) and intensity [17.8
      (1-233) and 5.3 (1-22)] of infestation. The recorded parasite fauna is
      represented by marine, brackish water, and probably also freshwater components.
      The brackish water environment of Segara Anakan does not prevent disease
      outbreaks due to parasitic copepods by preventing pathogenic marine or freshwater
      species to enter the lagoon. This might cause fish health problems if the Segara
      Anakan Lagoon would be developed for finfish mariculture in future.

PMID- 17219223
TI  - Language evolution as a Darwinian process: computational studies.
AB  - This paper presents computational experiments that illustrate how one can
      precisely conceptualize language evolution as a Darwinian process. We show that
      there is potentially a wide diversity of replicating units and replication
      mechanisms involved in language evolution. Computational experiments allow us to
      study systemic properties coming out of populations of linguistic replicators:
      linguistic replicators can adapt to specific external environments; they evolve
      under the pressure of the cognitive constraints of their hosts, as well as under
      the functional pressure of communication for which they are used; one can observe
      neutral drift; coalitions of replicators may appear, forming higher level groups
      which can themselves become subject to competition and selection.

PMID- 17219224
TI  - Hamstring tendons or patellar tendon as graft for ACL reconstruction?

PMID- 17219225
TI  - The effect of surface incongruity of grafted plugs in osteochondral grafting: a
      report of five cases.
AB  - Although grafted osteochondral plugs should ideally have a smooth surface for
      mosaicplasty, surface incongruity is sometimes evident at the time of surgery.
      There may be no problem if there is depression of the grafted plugs, but graft
      protuberance may have an adverse effect. We studied five knees in five patients
      who had incongruity (protuberance or depression) of grafted osteochondral plugs
      at the time of mosaicplasty. The mean age at surgery was 36.6 years (range, 15-65
      years), and the mean follow-up period was 32.9 months (range, 24-49 months). All
      patients underwent second-look arthroscopy after a mean post-surgical period of
      14.8 months (range, 3-18 months). We divided the cases so that there were two in
      the protuberant group (P) and three in the depressed group (D). In P, all
      patients had a catching sensation about 4 months after surgery, and sometimes
      pain in the knee joint. Second-look arthroscopy revealed fissuring of the plugs
      and fibrillation around the recipient site. In D, there were no symptoms due to
      the depressed plugs. Second-look arthroscopy showed that the depressed areas were
      covered with fibrocartilage-like tissue, and that the joint surface was smooth.
      In conclusion, our clinical results and second-look arthroscopic evaluation
      suggest that isolated osteochondral plug depressions of not greater than 1 mm
      could still promote acceptable cartilage healing leading to good clinical
      outcomes. However, plug protuberance at mosaicplasty should always be avoided.

PMID- 17219226
TI  - Early versus late start of open kinetic chain quadriceps exercises after ACL
      reconstruction with patellar tendon or hamstring grafts: a prospective randomized
      outcome study.
AB  - The purpose of the present investigation was to evaluate physical outcome after
      anterior cruciate ligament (ACL) reconstruction with early versus late initiation
      of open kinetic chain (OKC) exercises for the quadriceps in patients operated on
      either patellar tendon or hamstring grafts. Sixty-eight patients, 36 males and 32
      females, with either patellar tendon graft (34 patients) or hamstring graft (34
      patients) were enrolled in this study. All patients were randomly allocated to
      either early (the 4th postoperative week) or late (the 12th postoperative week)
      start of OKC exercises for the quadriceps, resulting in four subgroups: patellar
      tendon reconstruction, early start (P4) or late start (P12) of OKC quadriceps
      exercises, hamstring tendon reconstruction, early start (H4) or late start (H12)
      of quadriceps OKC exercises. Prior to surgery and 3, 5 and 7 months later,
      assessments of range of motion (goniometer), anterior knee laxity (KT-1000),
      postural sway (KAT 2000), thigh muscle torques (Kin-Com dynamometer) and anterior
      knee pain (anterior knee pain score) were evaluated. No significant group
      differences were found in terms of range of motion 3, 5 and 7 months
      postoperatively. The H4 group showed a significantly higher mean difference of
      laxity over time of 1.0 mm (CI: 0.18-1.86) than the P4 group (P=0.04). Within the
      same type of surgery, the H4 against the H12, the mean difference over time was
      1.2 mm (0.37-2.1) higher in the H4 group than in the H12 group (P=0.01). There
      were no significant group differences in terms of postural sway or anterior knee
      pain at the different test occasions. Significant differences in trends (changes
      over time) were found when comparing the four groups, for both quadriceps muscle
      torques (P<0.001) and hamstring muscle torques (P<0.001). All groups, except the
      P4 group, reached preoperative values of quadriceps muscle torques at the 7
      months follow-up. In the H4 and the H12 groups, significantly lower hamstring
      muscle torques at the 7 months follow-up compared with preoperative values were
      found. In conclusion, early start of OKC quadriceps exercises after hamstring ACL
      reconstruction resulted in significantly increased anterior knee laxity in
      comparison with both late start and with early and late start after bone-patellar
      tendon-bone ACL reconstruction. Furthermore, the early introduction of OKC
      exercises for quadriceps did not influence quadriceps muscle torques neither in
      patients operated on patellar tendon nor hamstring tendon grafts. On the
      contrary, it appears as if the choice of graft affected the strength of the
      specific muscle more than the type of exercises performed. Our results could not
      determine the appropriate time for starting OKC quadriceps exercises for patients
      who have undergone ACL reconstruction with hamstring tendon graft. Future studies
      of long-term results of anterior knee laxity and functional outcome are needed.

PMID- 17219227
TI  - Mathematical neuroscience.

PMID- 17219228
TI  - Measuring muscle lipids with 1H-MR spectroscopy.

PMID- 17219229
TI  - Transoral vertebral augmentation with polymethylmethacrylate in the treatment of
      a patient with a dens fracture nonunion and subarticular vertebral body fracture
      of C2.
AB  - The injection of polymethylmethacrylate (PMMA) is a minimally invasive, image
      guided procedure used to treat vertebral fractures due to osteoporosis,
      metastatic lesions, multiple myeloma, and benign but destabilizing bone tumors.
      The injection of PMMA into the C2 vertebral body using the transoral technique
      has been reported in three separate patients for treatment of benign tumors (a
      vertebral hemangioma and an aneurysmal bone cyst) and for multiple myeloma in the
      third patient. Although the injection of PMMA into the vertebral body is most
      commonly performed to treat benign vertebral compression fractures, a transoral
      C2 approach has not been reported in the English literature as a treatment for a
      benign fracture of C2. We report the treatment of a fracture and nonunion of the
      base of the dens and a subarticular fracture of the vertebral body of C2 using a
      bilateral transoral approach.

PMID- 17219230
TI  - Prospective evaluation of contrast-enhanced MR imaging after uncomplicated lumbar
      discography.
AB  - OBJECTIVE: Postdiscography infection is an uncommon complication. Magnetic
      resonance (MR) imaging is often the modality of choice for evaluating spinal
      infection. Discography entails disc access and fluid injection that could alter
      the baseline MR imaging appearance of the spine and be confounded for infection.
      Our purpose was to describe the MR imaging findings of the lumbar spine
      subsequent to uncomplicated discography and to determine if this may mimic
      infection. DESIGN AND PATIENTS: In a prospective cohort study of eight adults
      (age 22-64 years, mean 45 years) with 22 intradiscal injections, all subjects
      underwent routine unenhanced and contrast-enhanced MR imaging during the 2-3 week
      interval postdiscography. A subset of four returned for additional MR imaging
      during the 4-8 week interval postdiscography. MR images were reviewed for
      intradiscal, endplate, marrow, and epidural findings and then compared with
      prediscography examinations. Infection was excluded by clinical documentation.
      RESULTS: Postdiscography MR imaging showed that almost all levels were similar to
      baseline prediscography examinations. No levels developed new vertebral marrow
      edema, fluid-like intradiscal signal, endplate irregularity, or epidural
      abnormality. Two subjects simulated potential discitis, but these findings were
      unchanged from prediscography and were related to prior surgery. CONCLUSIONS:
      Uncomplicated lumbar spine discography does not cause MR imaging changes that
      simulate discitis.

PMID- 17219231
TI  - Longitudinal in vivo reproducibility of cartilage volume and surface in
      osteoarthritis of the knee.
AB  - OBJECTIVE: The aim of this study was to evaluate the longitudinal reproducibility
      of cartilage volume and surface area measurements in moderate osteoarthritis (OA)
      of the knee. MATERIALS AND METHODS: We analysed 5 MRI (GE 1.5T, sagittal 3D SPGR)
      data sets of patients with osteoarthritis (OA) of the knee (Kellgren Lawrence
      grade I-II). Two scans were performed: one baseline scan and one follow-up scan 3
      months later (96 +/- 10 days). For segmentation, 3D Slicer 2.5 software was used.
      Two segmentations were performed by two readers independently who were blinded to
      the scan dates. Tibial and femoral cartilage volume and surface were determined.
      Longitudinal and cross-sectional precision errors were calculated using the
      standard deviation (SD) and coefficient of variation (CV%=100x[SD/mean]) from the
      repeated measurements in each patient. The in vivo reproducibility was then
      calculated as the root mean square of these individual reproducibility errors.
      RESULTS: The cross-sectional root mean squared coefficient of variation (RMSE-CV)
      was 1.2, 2.2 and 2.4% for surface area measurements (femur, medial and lateral
      tibia respectively) and 1.4, 1.8 and 1.3% for the corresponding cartilage
      volumes. Longitudinal RMSE-CV was 3.3, 3.1 and 3.7% for the surface area
      measurements (femur, medial and lateral tibia respectively) and 2.3, 3.3 and 2.4%
      for femur, medial and lateral tibia cartilage volumes. CONCLUSION: The
      longitudinal in vivo reproducibility of cartilage surface and volume measurements
      in the knee using this segmentation method is excellent. To the best of our
      knowledge we measured, for the first time, the longitudinal reproducibility of
      cartilage volume and surface area in participants with mild to moderate OA.

PMID- 17219232
TI  - Myxoid chondrosarcoma in the calcaneus: a case report with MR imaging findings.
AB  - Skeletal myxoid chondrosarcoma is an extraordinarily rare neoplasm with a
      distinct histological morphology. Herein, we report a case of a myxoid
      chondrosarcoma in the calcaneus of a 20-year-old man with a description of its MR
      imaging (MRI) and histological findings.

PMID- 17219233
TI  - Pediatric concussions in sports; a simple and rapid assessment tool for
      concussive injury in children and adults.
AB  - BACKGROUND: We established a routine protocol for concussion evaluation in
      athletes for nonmedical personnel. The evaluation, management guidelines, and
      return-to-play recommendations were summarized with a memorable mnemonic on a
      convenient handheld card. MATERIALS AND METHODS: The ability to remember the
      return-to-play mnemonic and effectively apply it to corresponding guidelines was
      evaluated in 194 sports personnel without medical training. The participants were
      given three clinical scenarios, each including age, pertinent history, sporting
      event, description of an injury, symptoms, signs, and a brief neurological exam.
      Subsequently, the subject's ability to recall the return-to-play mnemonic and the
      Standard Assessment of Concussion, to describe the corresponding guidelines, and
      to advise return-to-play was evaluated. CONCLUSION: Our "return-to-play" mnemonic
      was found to be simple and memorable, allowing for a high recall percentage and
      accurate evaluation of concussion cases. High intersubject agreement suggests
      that this method has both standardization and generalization potential.

PMID- 17219234
TI  - Cystic angiomatosis of the craniocervical junction associated with Chiari I
      malformation: case report and review of the literature.
AB  - INTRODUCTION: Cystic angiomatosis of the skull and spine is an exceptionally
      rare, benign vascular lesion. Both the vertebral bones and the skull may be
      affected. Diagnosis and treatment of this disease is multidisciplinary.
      DISCUSSION: Histological examination is ultimately required to make a diagnosis.
      When the craniocervical junction is involved, the site of biopsy should be
      carefully selected so as to reduce procedure-related morbidity, including
      cerebrospinal fluid leakage and spinal deformity. We present a case report of a 4
      year-old boy with cystic angiomatosis of the skull base and upper cervical spine
      associated with a Chiari I malformation and provide a review of the pertinent
      literature.

PMID- 17219235
TI  - Restricted diffusion in Canavan disease.
AB  - INTRODUCTION: Canavan disease is a megalencephalic leukodystrophy due to
      deficiency of the enzyme aspartoacylase. Proton MR spectroscopy finding of
      elevated N-acetyl-L: -aspartate is considered diagnostic of Canavan disease. CASE
      REPORT: We report a case of Canavan disease, which showed restricted diffusion in
      diffusion-weighted imaging and discuss the cause of it.

PMID- 17219236
TI  - Accumulation of endosulfan in wild rat, Rattus norvegious as a result of
      application to soya bean in Mazoe (Zimbabwe).
AB  - An assessment of levels of endosulfan and endosulfan sulphate in rats collected
      from a plot sprayed with endosulfan was carried out for a period of four months.
      The analysis was carried out in the livers, muscles and fatty tissues of the rats
      using Gas Chromatography. Samples were ground with sodium sulphate and aluminium
      oxide and the analyte soxhlet extracted with hexane. The extract was then cleaned
      by florisil column chromatography. Levels of endosulfan in rats were found to
      range in livers from 0.356 to 5.807 ppb, in muscles from 0.089 to 5.167 ppb and
      in fatty tissues from 0.083 to 4.785 ppb. Levels of endosulfan sulphate
      correlated well with those of endosulfan and ranged in livers from 0.00 to 3.96
      ppb, in muscles from 0.00 to 3.37 ppb and in fatty tissue from 0.00 to 2.93 ppb.
      In the control rats samples, collected from an unsprayed area in the city of
      Harare (University of Zimbabwe), no endosulfan could be detected.

PMID- 17219237
TI  - Optimizing the monitoring strategy of wastewater treatment plants by
      multiobjective neural networks approach.
AB  - This paper applies artificial neural network (ANN) to model the observed effluent
      quality data. The ANN's structure, involving the number of hidden layer and node
      and their connection, is determined endogenously by resorting to the compromise
      of data cost minimization and prediction accuracy maximization. To obtain the
      best compromise possible, the model introduces an aspiration variable (micro)
      that represents the level of aspiration achieved in one objective and the
      conjugate of micro, (1 - micro), represents level of aspiration achieved in the
      other objective. Because a massive amount of calculation is required, the model
      applies genetic algorithm (GA) for its computational flexibility and capability
      to ensure global solution. Feasibility and practicality of the model is tested by
      a case study with a set of 150 daily observations on 17 operational variables and
      quality parameters at an industrial wastewater treatment plant (WTP) located in
      southern Taiwan. Of these 17 variables open to selection, only 6 variables,
      wastewater flow rate (Q), CN(-), SS, MLSS, pH and COD are selected by the model
      to achieve the maximum accuracy of prediction, 0.94, with a total cost of 5,950
      NT$. By constraining budget availability, the variables included in the model are
      reduced in number, causing a concomitant reduction in prediction accuracy, that
      is, by varying micro (aspiration level of accuracy), a trajectory of cost and
      accuracy is generated. The calculation results a cost of 3,650 NT$ and 0.54
      accuracy for the case with variables including flow rate, SCN(-) and SS in
      equalization basin; aeration tank hydraulic retention time (HRT) and percentage
      of returned sludge (R%) are selected for building the prediction model when the
      importance of required budget is equal to the accuracy of prediction model. In
      addition, when required cost for building ANN model is between 3,650 NT$ and
      3,900 NT$, the marginal return of budget input is highest in the entire range of
      calculation.

PMID- 17219238
TI  - Overview and forecast on forestry productions worldwide.
AB  - Our world is largely dependent upon the forestry productions. Through the
      exploitation of forest reserves, we manufacture various industrial products,
      furniture, and obtain fuel and energy. Forestry productions should be conducted
      without large-scale deforestation and environmental degradation. In present study
      we perform a review and forecast analysis on forestry productions worldwide, with
      the objectives of providing an insight into the trend for several types of
      forestry productions in the future, and providing referential data for
      sustainable forestry productions and environmental management. Polynomial
      functions are used to fit trajectories of forestry productions since 1961 and
      forecasts during the coming 20 years are given in detail. If the past pattern
      continues, world fibreboard production would dramatically grow and reach
      224,300,000 +/- 44,400,000 m(3) by the year 2020, an increase up to 240.7 to
      408.9% as compared to the present level. Roundwood production of the world would
      change by -55.5 to 70.4% and reach 3,526,600,000 +/- 2,066,800,000 m(3) by 2020.
      In 2020 world production of sawlogs and veneer logs would change by -100 to
      164.6% and reach 1,212,900,000 +/- 1,242,600,000 m(3). Global wood fuel
      production would change by -68.9 to 1.4% and reach 1,130,900,000 +/- 600,800,000
      m(3) by 2020. Forestry productions in developed countries would largely surpass
      productions in developing countries in the near future. World forestry production
      grew since 1961 excluding wood fuel. Roundwood and wood fuel account for the
      critical proportions in the forestry productions. Wood fuel production has being
      declined and rapid growing of roundwood production has slowed in recent years.
      Widespread use of regenerative wood substitutes and worldwide afforestation
      against deforestation will be among the most effective ways to reduce
      deforestation and environment degradation associated with forestry productions.

PMID- 17219239
TI  - Metal pollution assessment of surface sediments along a new gas pipeline in the
      Niger Delta (Nigeria).
AB  - Chromium, nickel, copper, zinc and cadmium were determined in sediments of the
      Niger Delta (Nigeria) in order to discriminate between natural metal sources and
      anthropogenic ones. Surface sediments were collected at seven sites along a new
      gas pipeline near Port Harcourt, between the New Calabar River and the Bonny
      River towards Bonny town. Chemical characterisation is obtained by hydrofluoric
      nitric acid digestion procedure, providing the 'total' ('residual') metal
      contents. Information about the anthropogenic metal fraction was obtained by cold
      diluted hydrochloric acid extraction procedure. This 'labile' acid soluble
      fraction of metals, perhaps due to relatively recent inputs in the sediments,
      constitutes the fraction more likely to be available to marine organisms, and
      furnishes a first evaluation of the possible toxicity of sediments of this
      sensitive ecosystem. Zinc appears to be the most available of all the heavy
      metals: its 'labile' fraction attains 40-50% of the 'total' zinc in sediment.
      Sites near Port Harcourt city are the most contaminated. All the examined metals
      are one order of magnitude below the respective values proposed as a limit for
      toxicity and are comparable with those observed by other authors in similar Niger
      Delta areas. Some anomalous data found near Port Harcourt city suggest that zinc
      and cadmium are the metals that require further monitoring. Their anthropogenic
      source could be derived from urban and industrial sewage.

PMID- 17219240
TI  - Useful plants of the semi-arid northeastern region of Brazil--a look at their
      conservation and sustainable use.
AB  - The use of native plants was examined in three rural communities in the semi-arid
      of the state of Pernambuco, in northeastern Brazil. The techniques employed in
      the present study combined a number of different techniques of data-gathering,
      including semi-structured interviews, guided tour, key-informants, and
      participating observation, and sampling of the vegetation to evaluate the
      biodiversity of useful plants. A total of 61 woody species were cataloged, mostly
      used for construction purposes or fuel. Among the species that stood out for
      their local importance and multiplicity of uses were: Myracrodruon urundeuva
      (Engl.) Fr. All., Schinopsis brasiliensis Engl., and Anadenanthera colubrina
      (Vell.) Brenan. The first two species are included in Brazilian lists of
      threatened species. Arguments are presented for strategies of management and
      conservation of plant resources in the semi-arid region that seek alternatives to
      the use of timber species and the development of alternative non-timber
      resources.

PMID- 17219241
TI  - Monitoring of biofilm-associated Legionella pneumophila on different substrata in
      model cooling tower system.
AB  - Cooling towers have the potential to develop infectious concentrations of
      Legionella pneumophila. Legionella counts increases where biofilm and warm water
      temperatures are present. In this study, biofilm associated L. pneumophila and
      heterotrophic bacteria were compared in terms of material dependence. Model
      cooling tower system was experimentally infected by L. pneumophila standard
      strain and monthly monitored. Different materials were tested for a period of 180
      days. The lowest L. pneumophila and heterotrophic plate counts were measured on
      plastic polymers, whereas L. pneumophila and heterotrophic bacteria were
      accumulated rapidly on galvanized steel surfaces. It can be concluded that
      selection of plastic polymers, as a manufacturing material, are suitable for
      recirculating water systems.

PMID- 17219242
TI  - Monitoring the trihalomethanes present in water after treatment with chlorine
      under laboratory condition.
AB  - In this work assays involving chlorinated water samples, which were previous
      spiked with humic substances or algae blue green and following the production of
      the THMs for 30 days is described. To implement the assays, five portions of
      1,000 ml of water were stored in glass bottles. The water samples were treated
      with solutions containing 2, 3, 4 and 5 mg l(-1) chlorine. The samples aliquots
      (60 ml) were transferred into the glass vials, 10 ml were removed to have a
      headspace and 100 microl of the 10 mg l(-1) pentafluortoluene bromide solution
      was added to each vial. The extraction step was performed by adding 10 g of
      Na(2)SO(4) followed by 5 ml of n-pentane. The vials were stopped with a TFE-faced
      septum and sealed with aluminum caps. The generated THMs were determined by gas
      chromatography with electron capture detector using reference solutions with
      concentration ranging from 8 to 120 microg l(-1) THMs. Three assays were
      monitored during 30 days and chloroform was the predominant compound found in the
      water samples, while other species of THMs were not detected. The results showed
      that when the chlorine concentration was increased in water samples containing
      algae the concentration of THM varied randomly. Nevertheless, in water samples
      containing humic substances the increase of the THM concentration presented a
      relationship with the chlorine concentration. It was also observed that
      chloroform concentration increased with the elapsed time up to one and six days
      to water samples spiked with humic substances and algae blue green, respectively
      and decreased along 30 days. By other hand, assays performed using water samples
      containing decanted algae material showed that THM was not generated by the
      chlorine addition.

PMID- 17219243
TI  - Air quality assessment in Delhi: before and after CNG as fuel.
AB  - A number of policy measures have been activated in India in order to control the
      levels of air pollutants such as particulate matter, sulphur dioxide (SO(2)) and
      nitrogen dioxide (NO(2)). Delhi, which is one of the most polluted cities in the
      world, is also going through the implementation phase of the control policies.
      Ambient air quality data monitored during 2000 to 2003, at 10 sites in Delhi,
      were analyzed to assess the impact of implementation of these measures,
      specifically fuel change in vehicles. This paper presents the impact of policy
      measures on ambient air quality levels and also the source apportionment. CO and
      NO(2) concentration levels in ambient air are found to be associated with the
      mobile sources. The temporal variation of air quality data shows the significant
      effect of shift to CNG (Compressed Natural Gas) in vehicles.

PMID- 17219244
TI  - Serial correlation and inter-annual variability in relation to the statistical
      power of monitoring schemes to detect trends in fish populations.
AB  - We studied the effects of inter-annual variability and serial correlation on the
      statistical power of monitoring schemes to detect trends in biomass of bream
      (Abramis brama) in Lake Veluwemeer (The Netherlands). In order to distinguish
      between 'true' system variability and sampling variability we simulated the
      development of the bream population, using estimates for population structure and
      growth, and compared the resulting inter-annual variabilities and serial
      correlations with those from field data. In all cases the inter-annual
      variability in the field data was larger than in simulated data (e.g. for total
      biomass of all assessed bream sigma = 0.45 in field data, and sigma = 0.03-0.14
      in simulated data) indicating that sampling variability decreased statistical
      power for detecting trends. Moreover, sampling variability obscured the inter
      annual dependency (and thus the serial correlation) of biomass, which was
      expected because in this long-lived population biomass changes are buffered by
      the many year classes present. We did find the expected serial correlation in our
      simulation results and concluded that good survey data of long-lived fish
      populations should show low sampling variability and considerable inter-annual
      serial correlation. Since serial correlation decreases the power for detecting
      trends, this means that even when sampling variability would be greatly reduced,
      the number of sampling years to detect a change of 15%.year(-1) in bream
      populations (corresponding to a halving or doubling in a six-year period) would
      in most cases be more than six. This would imply that the six-year reporting
      periods that are required by the Water Framework Directive of the European Union
      are too short for the existing fish monitoring schemes.

PMID- 17219245
TI  - In-vehicle measurement of ultrafine particles on compressed natural gas,
      conventional diesel, and oxidation-catalyst diesel heavy-duty transit buses.
AB  - Many metropolitan transit authorities are considering upgrading transit bus
      fleets to decrease ambient criteria pollutant levels. Advancements in engine and
      fuel technology have lead to a generation of lower-emission buses in a variety of
      fuel types. Dynamometer tests show substantial reductions in particulate mass
      emissions for younger buses (<10 years) over older models, but particle number
      reduction has not been verified in the research. Recent studies suggest that
      particle number is a more important factor than particle mass in determining
      health effects. In-vehicle particle number concentration measurements on
      conventional diesel, oxidation-catalyst diesel and compressed natural gas transit
      buses are compared to estimate relative in-vehicle particulate exposures. Two
      primary consistencies are observed from the data: the CNG buses have average
      particle count concentrations near the average concentrations for the oxidation
      catalyst diesel buses, and the conventional diesel buses have average particle
      count concentrations approximately three to four times greater than the CNG
      buses. Particle number concentrations are also noticeably affected by bus idling
      behavior and ventilation options, such as, window position and air conditioning.

PMID- 17219246
TI  - Chemical characteristics and source implications of petroleum hydrocarbon
      contaminants in the sediments near major drainage outfalls along the coastal of
      Laizhou Bay, Bohai Sea, China.
AB  - The associated industrial and urban developments are located to a large extent
      along the Laizhou Bay, Bohai Sea coastal and raw sewage is often discharged into
      near shore waters with little treatment. To find out chemical characteristics and
      pollution source of the petroleum related contaminations in sediments near the
      major drainage outfalls located in the coastal, in this study, 10 surface
      sediment samples were collected during June. Sediment samples were extracted by
      organic solvents, separated by silica gel column chromatography and the
      concentrations and the profiles of n-alkane, biomarker and PAH in sediments were
      analyzed by gas chromatography-mass selective detector (GC-MSD). The use of
      several molecular markers and related indexes derived for n-alkane and PAHs has
      been proposed for assessing the relative contributions to the environment of
      hydrocarbon sources. As a result, n-alkanes reflect that the sea area of paper
      mill (Station ZZ08) is dominated by vascular plant. DY petroleum oil field and
      outer shore of the paper mill (Station ZZ02) have some degrees of petroleum
      related hydrocarbon contamination. Whereas the contamination of the sea area of
      TH River may be ascribed to different sources such as territorial non-point
      pollution source, domestic sewages, and stormwater runoff. Judged by their PAH
      ratios, the sediments near the paper mill (Station ZZ02) and the outer station of
      the oil field (Staion TH2) were pyrolytic. The estuary of Tiao River including
      the inner Station THX, TH10 and TH05 are petrogenic. The marine sediment near DY
      drainage outfall may have a mixture source of PAH both pyrolytic and petrogenic.

PMID- 17219247
TI  - A passage through in vitro culture leads to efficient production of marker-free
      transgenic plants in Brassica juncea using the Cre-loxP system.
AB  - The Cre-loxP site-specific recombination system was deployed for removal of
      marker genes from Brassica juncea (Indian mustard). Excision frequencies,
      monitored by removal of nptII or gfp genes in F(1) plants of crosses between LOX
      and CRE lines, were high in quiescent, differentiated somatic tissues but
      extremely poor in the meristematic regions (and consequently the germinal cells)
      thus preventing identification and selection of marker-free transgenic events
      which are devoid of both the marker gene as well as the cre gene, in F(2)
      progeny. We show that a passage through in vitro culture of F(1 )leaf explants
      allows efficient development of marker-free transgenics in the F(2) generation
      addressing current limitations associated with efficient use of the Cre/loxP
      technology for marker gene removal.

PMID- 17219249
TI  - Phylogenetic analysis of LipL32 gene sequence of different pathogenic serovars of
      Leptospira.

PMID- 17219250
TI  - Transimmortalized proximal tubule and collecting duct cell lines derived from the
      kidneys of transgenic mice.
AB  - This review summarizes the strategy of cellular immortalization based on the
      principle of targeted oncogenesis in transgenic mice, used to establish models of
      transimmortalized renal proximal tubule cells, referred to as PKSV-PCT and PKSV
      PR-cells, and collecting duct principal cells, referred to as mpkCCD(cl4) cells.
      These cell lines have maintained for long-term passages the main biochemical and
      functional properties of the parental cells from which they were derived.
      Proximal tubule PKSV-PCT and PKSV-PR cells have been proved to be suitable cell
      systems for toxicological and pharmacological studies. They also permitted the
      establishment of a model of multidrug-resistant (MDR) renal epithelial tubule
      cells, PKSV-PR(col50), which have served for the study of both MDR-dependent
      extrusion of chemotherapeutic drugs and inappropriate accumulation of weak base
      anthracyclines in intracellular acidic organelles. The novel collecting duct cell
      line mpkCCD(cl4), which has maintained the characteristics of tight epithelial
      cells, in particular Na(+) absorption stimulated by aldosterone, has been
      extensively used for pharmacological studies related to the regulation of ion
      transport. These cells have permitted the identification of several aldosterone
      induced proteins playing a key role in the regulation of Na(+) absorption
      mediated by the epithelial Na(+) channel ENaC. Recent studies have also provided
      evidence that these cell lines represent valuable cell systems for the study of
      host-pathogen interactions and the analysis of the role of renal tubule
      epithelial cells in the induction of inflammatory response caused by uropathogens
      that may lead to severe renal damage.

PMID- 17219248
TI  - In vivo functions of mitogen-activated protein kinases: conclusions from knock-in
      and knock-out mice.
AB  - Multicellular organisms achieve intercellular communication by means of
      signalling molecules whose effect on the target cell is mediated by signal
      transduction pathways. Such pathways relay, amplify and integrate signals to
      elicit appropriate biological responses. Protein kinases form crucial
      intermediate components of numerous signalling pathways. One group of protein
      kinases, the mitogen-activated protein kinases (MAP kinases) are kinases involved
      in signalling pathways that respond primarily to mitogens and stress stimuli. In
      vitro studies revealed that the MAP kinases are implicated in several cellular
      processes, including cell division, differentiation, cell survival/apoptosis,
      gene expression, motility and metabolism. As such, dysfunction of specific MAP
      kinases is associated with diseases such as cancer and immunological disorders.
      However, the genuine in vivo functions of many MAP kinases remain elusive.
      Genetically modified mouse models deficient in a specific MAP kinase or
      expressing a constitutive active or a dominant negative variant of a particular
      MAP kinase offer valuable tools for elucidating the biological role of these
      protein kinases. In this review, we focus on the current status of MAP kinase
      knock-in and knock-out mouse models and their phenotypes. Moreover, examples of
      the application of MAP kinase transgenic mice for validating therapeutic
      properties of specific MAP kinase inhibitors, and for investigating the role of
      MAP kinase in pathogen-host interactions will be discussed.

PMID- 17219251
TI  - Osteopontin in metastatic lesions as a prognostic marker in ovarian cancers.
AB  - Osteopontin (OPN) is expressed in various human cancers and associated with tumor
      progression, invasion and metastasis in many manners. The purpose of this study
      is to investigate the clinical significance of OPN expression in metastatic
      lesions of ovarian cancers, since the prognosis of the patients with peritoneal
      dissemination is extremely poor. In primary tumors and peritoneal metastatic
      lesions from 40 patients with stage III ovarian cancers, the protein levels of
      OPN and histoscores were determined by enzyme immunoassay and
      immunohistochemistry, respectively. Immunohistochemical staining revealed OPN was
      distributed in the cytoplasm and nuclear compartments of the cancer and stromal
      cells within and around the tumor. The OPN level was significantly (p < 0.05)
      increased in 32 of 40 metastatic lesions of ovarian cancers. The OPN increased
      cases identified by immunohistochemical staining were consistent with those
      identified by the sandwich immunoassay. The prognosis of the 32 patients with
      significant increase of OPN in ovarian cancers was extremely poor, whereas the 36
      month survival rate of the 8 patients with no increase of OPN was 75%.
      Multivariate analysis revealed that the levels of OPN were independent predictors
      of prognosis from clinical characteristics (age, lesion size, histological
      types). OPN might be associated with peritoneal metastasis and its advancement,
      and that the OPN level in metastatic lesion may be a prognostic indicator in
      ovarian cancers.

PMID- 17219252
TI  - Follow-up after polypropylene mesh repair of anterior and posterior compartments
      in patients with recurrent prolapse.
AB  - To retrospectively analyze the outcome of surgery in women followed up for 1 year
      after vaginal repair with the Apogee (support of posterior vaginal wall) or
      Perigee (support of anterior vaginal wall) system. A total of 120 patients with
      recurrent cystocele and/or rectocele or with combined vaginal vault prolapse were
      treated by either posterior or anterior mesh interposition depending on the
      defect. Follow-up after 1 year (+/-31 days) comprised a vaginal examination with
      prolapse grading using the POP-Q system, measurement of vaginal length,
      evaluation of the vaginal mucosa, and exploration for mesh erosions.
      Postoperatively, 112 (93%) women were free of vaginal prolapse, whereas 8 (7%)
      had level 2 defects. Erosions occurred significantly more often (p = 0.042) in
      patients treated with the Perigee system. Our results suggest that the Apogee and
      Perigee repair systems (monofilament polypropylene mesh) yield excellent short
      term results after 1 year.

PMID- 17219253
TI  - The effect of mode of delivery, parity, and birth weight on risk of urinary
      incontinence.
AB  - To examine the relationship between symptoms of urinary incontinence (UI) and
      mode of delivery, parity, and birth weight, data were obtained from a population
      based random sample of 3,205 black, Hispanic, and white women age 30-79 in the
      Boston Area Community Health Survey. Measures include UI symptoms [>or=3
      (moderate/severe) Sandvik's severity index]; reproductive history [live birth(s),
      no live births, never pregnant]; mode of delivery for live births (>or=1 vaginal
      birth, cesarean delivery only); parity (1, 2, >or=3); and maximum birth weight of
      live births (<4,000 g, >or=4,000 g). Using logistic regression, women having
      >or=1 vaginal delivery had twice the odds of UI compared to women with no
      pregnancies (P = 0.002) or only cesarean deliveries (P = 0.032). There was no
      difference in odds of UI between cesarean delivery only and never pregnant, by
      parity or birth weight. Vaginal delivery contributes to risk of UI for black,
      Hispanic, and white women.

PMID- 17219254
TI  - A simple teaching tool for training the pelvic organ prolapse quantification
      system.
AB  - The pelvic organ prolapse quantification (POPQ) system is currently the most
      common and specific system describing different prolapse stages. Nevertheless,
      its use is not yet accepted worldwide in routine care. Our aim was to develop a
      simple teaching tool for the POPQ system capable of simulating different stages
      of uterovaginal prolapse for use in medical education with hands on training. We
      constructed a moveable and flexible tool with an inverted Santa Claus' cap, which
      simulated the vaginal cuff and the tassel at the end representing the cervix. A
      wooden embroidery frame fixed the cap and served as the hymen, the reference
      point for all measurements. Inside the cap, we sewed buttons to define the
      anatomic landmark points Aa and Ap located 3 cm distal from the frame. After
      explaining the device to the students, we used the three-by-three grid for
      recording the quantitative description of the pelvic organ support. First, each
      student had to demonstrate a specific prolapse with his cap device. Then, a
      prolapse was simulated on the cap, and the student had to take the relevant
      measurements and record them in the POPQ grid. The main training effect to
      understand the POPQ system seems to be the possibility for each trainee to
      simulate a three-dimensional prolapse with this flexible vagina model.

PMID- 17219256
TI  - Combined cytoreductive laser therapy and immunotherapy for palliation of
      metastatic renal cell carcinoma to the head and neck.
AB  - Interleukin-2 (IL-2) remains the mainstay of treatment for metastatic renal cell
      carcinoma (RCC), but minimally invasive surgical techniques have provided new
      options for the combined treatment of RCC. Two patients with metastatic RCC to
      the head and neck treated by combined laser-induced thermal therapy and IL-2 were
      described in this case report. Both patients had an extended survival compared to
      the historical survival of 10 months for metastatic RCC but eventually succumbed
      to progressive disease. The authors' initial experience with metastatic RCC
      suggests that laser thermoablation and immunotherapy in selected patients with
      metastatic RCC is warranted as a palliative treatment, but a larger study with
      long-term follow-up is necessary to determine the effectiveness of this approach.

PMID- 17219257
TI  - Distribution of diatoms in relation to land use and pH in blackwater coastal
      plain streams.
AB  - We compared the composition of diatom assemblages collected from New Jersey
      Pinelands blackwater streams draining four different land uses, including forest
      land, abandoned-cranberry bogs, active-cranberry bogs, and developed and upland
      agricultural land. Over a 2-year period (2002-2003), we collected 132 diatom taxa
      at 14 stream sites. Between-year variability in the composition of stream samples
      was high. Most diatom species were rarely encountered and were found in low
      abundance. Specific conductance and pH were higher at developed/agricultural
      sites compared with all other site types. Neither species richness nor genus
      richness was significantly different between stream types. However, clear
      community patterns were evident, and a significant difference in species
      composition existed between the developed/agricultural sites and both cranberry
      and forest sites. The primary community gradient, represented by the first axis
      of a DCA ordination, was associated with variations in pH and specific
      conductance. Although community patterns revealed by ordinating the data
      collected in 2002 differed from those obtained using the 2003 data, both
      ordinations contrasted the developed/agricultural sites and the other sites.
      Acidobiontic and acidophilous diatoms characterized the dominant species at
      forest, abandoned-bog, and cranberry sites, whereas indifferent species dominated
      the developed/agricultural samples. Although our study demonstrated a
      relationship between the composition of diatom assemblages and watershed
      conditions, several factors, including taxonomic problems, the large number of
      diatom species, incomplete pH classifications, and year-to-year variability may
      limit the utility of diatom species as indicators of watershed conditions in the
      New Jersey Pinelands.

PMID- 17219255
TI  - Er:YAG laser therapy for peri-implant infection: a histological study.
AB  - The purpose of this study was to evaluate the effects of Er:YAG laser on
      degranulation and implant surface debridement in peri-implant infection. The peri
      implant infection was experimentally induced in dogs, and the treatment was
      performed using an Er:YAG laser or a plastic curet. Animals were sacrificed after
      24 weeks, and undecalcified histological sections were prepared and analyzed.
      Degranulation and implant surface debridement were obtained effectively and
      safely by Er:YAG laser. Histologically, a favorable formation of new bone was
      observed on the laser-treated implant surface, and the laser group showed a
      tendency to produce greater bone-to-implant contact than the curet group. These
      results indicate that the Er:YAG laser therapy has promise in the treatment of
      peri-implantitis.

PMID- 17219258
TI  - Human impacts on land cover and water balances in a coastal Mediterranean county.
AB  - We analyzed the effects of changes in land cover on the water balance in Spain's
      Marina Baixa County, on the Mediterranean coast. To reveal how different land
      management strategies have affected the area's environment, four municipalities
      within the same catchment were studied: Benidorm, Callosa d'en Sarria, Beniarda,
      and Guadalest. In the municipalities of Callosa and Benidorm, the proportion of
      the area covered by woodland declined by 4.2% and 30.2%, respectively, and
      woodland was replaced by agriculture and urban development. The abandonment of
      farmland produced a 17% increase in the proportion of the area covered by
      vegetation in Guadalest and Beniarda, where frequent forest fires have
      exacerbated a decrease in the area of pine woodland. Tourism development in
      Benidorm has been accompanied by an increase in the transportation infrastructure
      and by an expansion of areas with an impermeable surface, with the lowest level
      of infiltration into the aquifer system. These changes have generated a net water
      deficit in Callosa and Benidorm of more than 6 Mm(3)/year, creating a high demand
      for water imported from other municipalities (Guadalest and Beniarda) or from
      outside of the county to maintain the sustainability of the current water
      management strategies. The Marina Baixa case study is representative of many of
      the world's coastal areas that are undergoing rapid urban development based on an
      inappropriate understanding of human progress based mainly on economic
      development and thus provides insights into water management in other areas.

PMID- 17219264
TI  - Pyloroplasty with fundoplication in the treatment of combined gastroesophageal
      reflux disease and bloating.
AB  - BACKGROUND: Although gastroparesis does not influence gastroesophageal reflux
      disease (GERD) or antireflux surgery, many patients with GERD will also suffer
      from gastroparesis-related bloating as a distinct symptom different from GERD
      related symptoms. The purpose of this study was to assess whether a pyloroplasty
      with a fundoplication will improve bloating symptoms in these patients. METHODS:
      A prospectively gathered database of all patients undergoing antireflux surgery
      was reviewed. All patients underwent history, physical examination, upper
      gastrointestinal endoscopy, esophageal manometry, 24-hour esophageal pH
      monitoring, and, selectively, contrast upper gastrointestinal radiography.
      Patients with symptoms of bloating also underwent gastric emptying scintigraphy.
      All patients completed the GERD-Health Related Quality of Life (HRQL) symptom
      severity questionnaire. One of the items of this instrument relates to bloating.
      The item is scored from 0 (asymptomatic) to 5 (incapacitating) based on
      descriptive anchors. Patients with symptomatic GERD and objective findings by
      physiologic testing were offered antireflux surgery. Those with delayed gastric
      emptying (defined as T(1/2) > 120 minutes) were also offered a pyloroplasty.
      Operations performed included a laparoscopic or open Nissen or Toupet
      fundoplication with a Heineke-Mickulicz pyloroplasty. Postoperatively, patients
      completed the GERD-HRQL and had a gastric emptying scintigraphy performed.
      RESULTS: Three-hundred and sixty-nine patients underwent antireflux surgery; of
      these, 35 patients also had a pyloroplasty. Twenty-eight (80%) of these patients
      reported significant symptomatic improvement. The median preoperative bloating
      score improved from 4 to 1 postoperatively (P < 0.05), and the median gastric
      emptying scintigraphy T(1/2) improved from 244 to 112 minutes (P < 0.05).
      CONCLUSIONS: Although gastroparesis may not contribute to symptoms of GERD, it
      can contribute to symptoms of bloating. Bloating symptoms improved in 80% of
      patients with the addition of a pyloroplasty. Therefore, addition of pyloroplasty
      to a fundoplication in patients with gastroparesis-related bloating can improve
      bloating symptoms.

PMID- 17219267
TI  - Experimental comparison of monofile light and heavy polypropylene meshes: less
      weight does not mean less biological response.

PMID- 17219265
TI  - Lateral and mediastinal lymph node dissection in differentiated thyroid
      carcinoma: indications, benefits, and risks.
AB  - BACKGROUND: There are 3 compartments of regional lymph nodes to which thyroid
      carcinoma metastasizes: central, lateral, and mediastinal compartments. The
      central compartment is the nearest to the thyroid and usually dissected
      routinely. However, the indication for dissection of the lateral and mediastinal
      compartments for differentiated thyroid carcinoma remains an open question.
      METHODS: The indication for dissection of lateral and mediastinal compartments is
      evaluated based on previous reports, including those from our department.
      RESULTS: There is nothing controversial about the indication for therapeutic
      lateral node dissection for tumors with clinically apparent lateral node
      metastasis. Such cases are more likely to show recurrence, especially in
      previously dissected compartments, and surgeons must perform dissection
      carefully. Although there are no randomized studies on the indication for
      prophylactic lateral node dissection, it is recommended for papillary carcinoma
      with aggressive characteristics such as large size and massive extrathyroid
      extension. Prophylactic mediastinal dissection via median sternotomy is not
      recommended. CONCLUSIONS: Node dissection of the lateral and mediastinal
      compartments must be performed aggressively and radically to prevent recurrence
      in previously dissected regions.

PMID- 17219270
TI  - Malignant nonfunctioning endocrine tumors of the pancreas: predictive factors for
      survival after surgical treatment.
AB  - BACKGROUND: There are scant studies that have analyzed the prognostic factors for
      malignant nonfunctioning endocrine tumors of the pancreas. We identified the
      predictive factors associated with long-term survival after surgical resection
      for malignant nonfunctioning endocrine tumors. METHODS: Among the 25 patients
      seen at our hospital with a diagnosis of malignant nonfunctioning endocrine
      tumor, a review was performed on 22 of these patients who were surgically treated
      at our institution over the last 10 years. The following factors were evaluated
      for disease-specific mortality: age, gender, tumor location, tumor size,
      histological differentiation, status of the resection margin, and status of lymph
      node involvement. RESULTS: Tumor recurrence was noted in 9 cases (40.9%) among
      the 22 operated patients. Of the 9 recurrent cases, 7 patients (77.8%) had liver
      metastases. The median follow-up period was 24.8 (range: 3.7-121.4) months. The
      overall actuarial 1-, 2- and 5-year survival rates were 84.1%, 72.5%, and 52.8%,
      respectively. The factor shown to have a favorable independent prognostic
      significance was a negative resection margin (odds ratio = 19.44, 95% confidence
      interval = 1.22-310.54, P = 0.036). CONCLUSIONS: Definitive surgical resection of
      the primary tumor was a predictor of long-term survival after surgical resection
      for malignant nonfunctioning endocrine tumor.

PMID- 17219271
TI  - Safety and efficacy of surgical management of hyperthyroidism: 15-year experience
      from a tertiary care center in a developing country.
AB  - BACKGROUND: Ideal management of toxic goiter still remains elusive. Though
      surgical management of toxic multinodular goiter (MNG) is well accepted, surgical
      treatment of Graves' disease (GD) is still controversial in view of the presumed
      increased incidence of complications. In this paper, we discuss the experience of
      the surgical management of hyperthyroidism at a specialized tertiary care
      endocrine center in a developing country, highlighting the minimal morbidity and
      satisfactory outcome in experienced hands. MATERIALS AND METHODS: We
      retrospectively reviewed 325 consecutive patients with hyperthyroidism managed
      surgically from 1990 to 2005. The etiologic diagnoses were Graves' disease (185),
      toxic MNG (105), and autonomously functioning thyroid nodules (AFTN) (n = 35).
      The indications for surgery in Graves' patients were large goiter, relapse after
      antithyroid drug therapy (ATD), Graves' ophthalmopathy, and presence of nodule.
      The indications for surgery in toxic MNG were retrosternal extension (n = 15),
      compressive symptoms (n = 20), and large size (grade II). Among the AFTN nodule
      size, those greater than 4 cm (85%) formed the major indication for surgery.
      Subjects with GD and toxic MNG were subjected to subtotal thyroidectomy (n = 93
      prior to 1995) or total thyroidectomy (n = 205 post-1995). Hemithyroidectomy was
      the procedure of choice in patients with AFTN. RESULTS: Patients with Graves'
      disease were younger in age, with shorter mean duration of goiter when compared
      with the other 2 groups. Eight percent of patients with Graves' disease without a
      clinically palpable nodule and 25% of those with nodules had associated
      differentiated carcinoma, including papillary, follicular, and medullary thyroid
      cancer. Four percent of patients with toxic MNG had malignancy. Complications
      included temporary hypocalcemia (24%), permanent hypocalcemia (3%), and permanent
      vocal-cord palsy (1%). CONCLUSIONS: Surgery for hyperthyroidism has negligible
      mortality and acceptable morbidity in experienced hands. It is a definite option
      in selected cases. Immediate and permanent cure of hyperthyroidism is achieved,
      with no recurrences, after total thyroidectomy. The cosmetic outcome is good,
      with excellent patient satisfaction and acceptance.

PMID- 17219272
TI  - Ethical misconduct in publishing: the authors' perspective.

PMID- 17219273
TI  - Mechanisms of hepatic regeneration following portal vein embolization and partial
      hepatectomy: a review.
AB  - BACKGROUND: Portal vein embolization (PVE) improves outcome following major
      hepatectomy, and basic studies have presented evidence related to the mechanisms
      responsible for hepatic regeneration. Hemodynamic changes following PVE are
      similar to, but slightly different from, those of partial hepatectomy (PH)
      because arterial flow to the embolized lobe is preserved. However, the process of
      hepatic regeneration is essentially the same after both PVE and PH. A number of
      mediators are involved in PVE or PH-induced hepatic regeneration. These include
      inflammatory cytokines, vasoregulators, growth factors, eicosanoids, and various
      hormones. These mediators activate a complex network of signal transduction that
      promotes hepatic regeneration. A variety of conditions have been shown to
      modulate the function of these mediators and inhibit regeneration. These include
      biliary obstruction, diabetes, chronic ethanol consumption, malnutrition, gender,
      aging, and infection. CONCLUSION: Optimizing these factors, where possible,
      before PVE or PH, is essential to maximize hypertrophy of the liver. A fuller
      understanding of hepatic physiology and pathophysiology following PVE or PH may
      lead to greater functional capacity of the remaining liver and extend the
      indications for hepatectomy in patients who require large liver volume resection.

PMID- 17219274
TI  - Clinicopathologic features of hepatocellular carcinoma patients with compensated
      cirrhosis surviving more than 10 years after curative hepatectomy.
AB  - BACKGROUND: The aim of this study was to clarify the clinicopathologic features
      of hepatocellular carcinoma (HCC) patients with compensated cirrhosis surviving
      more than 10 years after initial hepatectomy. STUDY DESIGN: Among 250 patients
      who underwent hepatectomy for HCC between 1987 and 1994 at our institute, 145
      patients who had Child-Pugh class A liver function and who underwent curative
      resection were included in this study. Clinicopathologic factors in 10-year
      survivors and patients who died within 10 years (nonsurvivors) were compared, and
      the prognostic factors affecting survival were identified. RESULTS: There were 29
      patients who survived for more than 10 years after initial hepatectomy, and 9 of
      those patients survived without cancer recurrence. The 3-, 5-, and 10-year
      survival rates were 76.2%, 53.0%, and 26.9% respectively. The corresponding
      disease-free survival rates were 43.1%, 25.7%, and 9.9% respectively. In
      multivariate analysis, liver fibrosis grade F0-2, female gender, ICG-R15 value of
      less than 15%, and absence of microscopic vascular invasion were favorable
      independent factors associated with 10-year survival. Disease-free interval after
      initial hepatectomy in 10-year survivors with recurrence was significantly longer
      than that in nonsurvivors with recurrence, 5.1 and 1.9 years respectively (P =
      0.0004). The number of intrahepatic recurrent nodules in 10-year survivors tended
      to be fewer than that in nonsurvivors. CONCLUSIONS: Based on the results of our
      study, liver fibrosis grade F0-2, female gender, ICG-R15 value of less than 15%
      and absence of microscopic vascular invasion at initial hepatectomy might be
      biologically favorable conditions for long-term survival. Close follow-up as well
      as multimodal treatment could contribute to prolongation of survival in such
      patients, even if HCC recurrence develops.

PMID- 17219275
TI  - Lymph node ratio is more valuable than level III involvement for prediction of
      outcome in node-positive breast carcinoma patients.
AB  - BACKGROUND: We examined the relationship between different expressions of
      positive axillary lymph nodes (PN) and the outcomes of node-positive breast
      carcinoma patients to determine the best predictor(s) among these expressions and
      to assess whether anatomic high level involvement is an independent prognostic
      factor. STUDY DESIGN: In this retrospective study, the primary endpoints were
      distant recurrence (DR), locoregional recurrences (LRR), and disease-free
      survival (DFS). Univariate and multivariate prognostic factor analyses were
      carried out using survival and regression methods in the data of 704 patients
      with PN. RESULTS: In multivariate analysis, the number of PN, ratio of PN, log
      odds of PN, and level III (L-III) involvement, separately, were significant
      factors for DR in addition to age, tumor size, and lymphovascular invasion (LVI).
      In the final model including all expressions of nodal involvement, age
      (continuous P = 0.001; hazard ratio [HR]: 0.98; 95% confidence Interval [95% CI]:
      0.96-0.99), tumor size (continuous: P < 0.0001; HR: 1.3; 95% CI, 1.2-1.5), LVI
      (yes vs. no: P = 0.005; HR: 1.6; 95% CI, 1.2-2.2), and ratio of PN (continuous: P
      = 0.02; HR: 1.03; 95% CI, 1.01-1.06) were the independent prognostic factors for
      DR. For LRR, ratio of PN (continuous: P = 0.001; HR: 1.02; 95% CI, 1.01-1.03) was
      the most important factor in addition to age (continuous: P = 0.02; HR: 0.98; 95%
      CI, 0.97-0.99) and tumor size (continuous: P = 0.04; HR: 1.3; 95% CI, 1.1-1.6).
      When patients were stratified by number categories of PN (1-3 vs. 4-9 vs. >/=
      10), there was no difference between DFSs of patients with and without L-III
      involvement. In contrast, when patients were stratified by L-III involvement,
      DFSs according to the number categories were statistically different.
      CONCLUSIONS: Ratio of PN was more valuable than number of PN for predicting
      outcome in node-positive breast carcinoma patients. Level III involvement was not
      an independent prognostic indicator either for locoregional or for distant
      recurrences.

PMID- 17219276
TI  - Positron emission tomography in relation to Noguchi's classification for
      diagnosis of peripheral non-small-cell lung cancer 2 cm or less in size.
AB  - BACKGROUND: F-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET)
      scanning has become a critically important tool in diagnosis and management of
      non-small-cell lung cancer. However, the effectiveness of (18)F-FDG-PET as a
      diagnostic tool for small-sized lung cancer is controversial. The purpose of this
      study was to examine the accuracy of( 18)F-FDG-PET in relation to Noguchi's
      classification in the diagnosis of small peripheral non-small-cell lung cancer.
      METHODS: Between January 2003 and April 2006, 150 patients with peripheral lung
      lesions who were undergoing chest computed tomography (CT),( 18)F-FDG-PET, and
      operation were analyzed. RESULTS: Eighty-three patients had malignant lesions,
      and 67 patients had benign lesions. PET had a sensitivity, specificity, positive
      predictive value, and negative predictive value of 75.9%, 64.1%, 72.4%, and
      68.3%, respectively. In 37 patients with peripheral lung cancer measuring 2.0 cm
      or less in the greatest diameter, the sensitivity was 51.4% and the specificity
      was 51.9%. Among them, all 4 cases of Noguchi type A adenocarcinoma [localized
      bronchioloalveolar carcinoma (LBAC)], 4 of 5 type B and 8 of 17 type C were false
      negative, while 9 of 11 (81.8%) types D, E, and F (invasive carcinomas without a
      BAC component) were true positive. CONCLUSION: The accuracy of( 18)F-FDG-PET is
      generally low in distinguishing malignancy from benign lesions in small lesions
      (<2.0-cm diameter). The significance of PET as a diagnostic tool is small,
      especially when the tumor has a ground-glass component at a high rate. The
      sensitivity of PET is high in small invasive carcinomas without a BAC component,
      but it is difficult to distinguish carcinoma from benign tumor from its image.

PMID- 17219277
TI  - Impact of lymph node micrometastasis in patients with pancreatic head cancer.
AB  - PURPOSE: The purpose of this study was to investigate the clinical significance
      of nodal micrometastasis in patients who underwent a curative operation for
      pancreatic cancer. EXPERIMENTAL DESIGN: Fifty-eight patients underwent a
      macroscopically curative resection with extended lymph node dissection for
      pancreatic cancer. The total number of resected lymph nodes was 1,058, and 944
      histologically negative lymph nodes were subjected to immunohistochemical
      staining to detect occult micrometastases. RESULTS: Nodal micrometastases were
      detected immunohistochemically in 147 out of 944 resected histologically negative
      lymph nodes (15.6%). Forty-four of all 58 patients (75.9%) and 13 of the 23
      histologically node-negative patients (56.5%) had nodal micrometastases. Nodal
      micrometastases existed in the N1 lymph node area most frequently, followed by
      the N2 and N3 lymph node areas. The distribution was similar to that of
      histologically metastatic lymph nodes. Ten out of 16 patients (62.5%) with
      histological N1, and 5 out of 16 patients (31.3%) with histological N2 had nodal
      micrometastases beyond the histological lymph node status. Three and 5-year
      survival rates of pN0 patients without lymph node nodal micrometastases were both
      60.0%, while those with nodal micrometastases were 19.2% and 0%, respectively.
      There was statistically significant difference between the both groups (P =
      0.041). CONCLUSIONS: Nodal micrometastasis in pancreatic cancer existed in wider
      and more distant areas than histological lymph node status, and it was an
      unfavorable predictive factor, even in N0 patients.

PMID- 17219278
TI  - Special anoscope for easy purse-string suture application in stapled
      hemorrhoidopexy.
AB  - BACKGROUND: Internal hemorrhoids and loose rectal mucosa may block exposure
      during the purse-string suturing in stapled hemorrhoidopexy, and this may lead to
      complications. MATERIALS AND METHODS: To retract the prolapsing rectal mucosa, we
      modified the purse-string anoscope of the PPH01 kit (Ethicon-Endosurgery,
      Cincinnati, OH, USA) and produced a special anoscope. The open part of the purse
      string suture anoscope is covered by transparent acrylic (Orthoacryl, Dentaurum,
      Pforzheim, Germany). The covering had completely cylindrical outer and inner
      surfaces and was thin enough to let the anoscope easily rotate in the anal
      dilator and to let the 26 mm curved, round-bodied needle of the 2/0 polypropylene
      suture move in the anoscope. A window, 3 cm long and 3-4 mm wide, was opened at
      the angled part of the anoscope 2 cm to the tip. This special anoscope was used
      for the purse-string suture during the stapled hemorrhoidopexy procedure in five
      patients. RESULTS AND CONCLUSIONS: No postoperative complications, early or late,
      were encountered, and we propose that stapled hemorrhoidopexy procedure can be
      applied more easily by using this special anoscope.

PMID- 17219279
TI  - Recurrent renal hyperparathyroidism caused by parathyromatosis.
AB  - BACKGROUND: Parathyromatosis is defined as multiple foci of benign
      hyperfunctioning parathyroid tissue in the neck or mediastinum. Parathyromatosis
      is a problematic cause of recurrent hyperparathyroidism (HPT). In renal HPT, the
      stimuli of the parathyroid cells persist after parathyroidectomy (PTx), and for
      this reason, parathyromatosis might be important in renal HPT. METHODS: Between
      July 1973 and December 2005, 1,932 patients underwent PTx for advanced renal HPT
      in our department. We evaluated the frequency, clinical findings and the
      prognosis of this kind of parathyroid disorder. RESULTS: After total PTx with
      forearm autograft for renal HPT, which was performed initially in our department,
      the risk for developing parathyromatosis was 0.11% (2/1837); after sub-total PTx,
      it was 5% (1/20). The risk for developing parathyromatosis was lower after total
      PTx with forearm autograft than after sub-total PTx (P < 0.05). In patients who
      developed persistent or recurrent HPT and were referred to our department for
      neck re-operation, parathyromatosis occurred in 12.1% (7/58); in those originally
      operated on at our hospital, the corresponding figure was 7.1% (3/42). This
      difference was not significant (P = 0.42). Only in 4 of 10 patients was
      parathyromatosis suggested before re-operation. However, in spite of several re
      operations, high parathyroid hormone (PTH) levels persisted in 6 of 10 patients
      with parathyromatosis. CONCLUSION: Parathyromatosis is a non-negligible cause of
      recurrent renal HPT in patients who require neck re-exploration. Parathyromatosis
      is difficult to diagnose pre-operatively and completely controlled by re
      operation. Parathyromatosis should be kept in mind when performing neck re
      exploration for recurrent renal HPT.

PMID- 17219280
TI  - Assessment of anal sphincter function by Sengstaken-Blakemore tube anal
      manometry.
AB  - BACKGROUND: Anal manometry is a useful tool for testing the effectiveness of
      surgical treatment. However, most techniques for anal pressure measurement are
      not easily available because of high cost. The aim of the present study was to
      introduce an easy and reproducible method for measuring anal pressures in testing
      the effectiveness of surgical procedures. MATERIALS AND METHODS: We used a
      Sengstaken-Blakemore tube connected to a mercury manometer. After calibration of
      the system by inflating the distal (gastric) balloon and filling connection lines
      to the mercury manometer with 0.9% NaCl solution, resting and squeezing anal
      pressures were measured. The system was used on 50 human subjects (35 with anal
      fissure and 15 normal volunteers). Left lateral internal sphincterotomy had been
      performed in the anal fissure cases. Anal pressures were measured preoperatively
      and on postoperative days (POD) 2 and 20. RESULTS: Preoperative resting anal
      pressures in the group with anal fissure (83.4 +/- 1 mmHg) were significantly
      higher than those in the group of normal individuals (52 +/- 1.2 mmHg; p =
      0.001). Resting anal pressures after the sphincterotomy (29 +/- 1 mmHg) were
      found to be significantly lower on POD 2, and resting anal pressure measurements
      (47 +/- 1 mmHg) on POD 20 were lower than the corresponding preoperative values.
      These values are closer to those of normal volunteers (p = 0.016). CONCLUSIONS:
      Anal manometry can be performed with this easily constructible and inexpensive
      system. This reproducible method can be used in the assessment of the results of
      surgical treatment in patients with anal and perianal diseases.

PMID- 17219281
TI  - Laparoscopic appendectomy: differences between male and female patients with
      suspected acute appendicitis.
AB  - BACKGROUND: The role of laparoscopy in the management of patients with suspected
      acute appendicitis remains controversial. It has been suggested that laparoscopy
      is useful mainly in young women of reproductive age because of the high incidence
      of wrong diagnosis in these patients. METHODS: Different management protocols for
      patients with suspected acute appendicitis were prospectively used in male and
      female patients; women of reproductive age were treated laparoscopically, while
      men were randomised to open or laparoscopic appendectomy. RESULTS: From September
      2002 to September 2005, 132 patients-54 women and 78 men-with suspected acute
      appendicitis were treated according to the protocol. The incidence of wrong
      diagnosis in female patients was high (26% and the conversion rate low (5.5%). In
      contrast, in the laparoscopic male subgroup, these rates showed a reverse
      relationship (5.2% and 18.5%, respectively). Morbidity did not differ between
      female and male patients or between the 2 arms of the male group. Laparoscopic
      appendectomy took longer to perform without affecting significantly the needs for
      postoperative analgesia, the duration of hospital stay and the time to return to
      normal activities when compared with open appendectomy in men. CONCLUSION:
      Laparoscopic appendectomy is at least as safe as the open procedure in the male
      population, although it does not appear to offer any obvious advantage over the
      open procedure. The diagnostic advantage that laparoscopy offers to fertile women
      makes the procedure attractive for this population.

PMID- 17219282
TI  - Clinical significance of large tenascin-C spliced variant as a potential
      biomarker for colorectal cancer.
AB  - BACKGROUND: Tenascin-C is an extracellular matrix protein forming various types
      of spliced variants. Low molecule variants are transiently present, but large
      spliced variants are predominantly overexpressed in proliferative processes or
      tumorigenesis in some varieties of cancer. However, the detection of the plasma
      level of large tenascin-C spliced variant (L-Tn-CSV) in colorectal cancer (CRC)
      has not been clarified. This study was performed to validate elevated plasma L-Tn
      CSV levels as a possible biomarker for CRC. MATERIALS AND METHODS: Plasma samples
      were obtained before resection and from time to time postoperatively and stored
      at -80 degrees C until assay. Plasma L-Tn-CSV levels were evaluated in patients
      with primary (n = 162) and with recurrent (n = 20) CRC, including 48 healthy
      volunteers, measured by ELISA. RESULTS: The average plasma L-Tn-CSV
      concentrations of patients with primary CRC were 5,260 +/- 3,243.3 pg/ml and of
      patients with recurrent CRC 4,106 +/- 2,261.1 pg/ml, which were significantly
      elevated in comparison with those of healthy volunteers (2,364.3 +/- 7,49.6). The
      sensitivity for detecting CRC using plasma L-Tn-CSV was 56.6%, based on the mean
      +/- 2 SD of the concentrations of healthy controls (3,863.5), which was
      significantly higher than CEA (40.1%) and CA19-9 (23.6%). No obvious associations
      were evident between plasma L-Tn-CSV status and values of CEA and CA19-9
      respectively. Statistically significant differences in plasma L-Tn-CSV were
      observed depending on tumor depth, lymph node metastasis, and TNM stage. Negative
      conversions of plasma L-Tn-CSV levels 6 months after resection were significantly
      higher in the completely curative resection group than in the non-curative groups
      (P < 0.001). CONCLUSION: The plasma L-Tn-CSV may serve very well as a useful
      biomarker for tumor staging and postoperative monitoring of preoperatively
      positive CRC that is independent and exceeds conventional tumor markers.

PMID- 17219283
TI  - Rural surgery in southern Sudan.

PMID- 17219285
TI  - High expression of plasminogen activator inhibitor-2 (PAI-2) is a predictor of
      improved survival in patients with pancreatic adenocarcinoma.
AB  - OBJECTIVE: Recent findings suggest that the urokinase-type plasminogen activator
      (uPA), its receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and -2
      (PAI-2) play key roles in cancer invasion. The prognostic value of components of
      this system is well established in breast cancer. However, little is known of its
      involvement in pancreatic cancer (PC). METHODS: Quantitative real-time polymerase
      chain reaction (Q-RT-PCR) was used on tissue-banked specimens and
      immunohistochemistry (IHC) on paraffin specimens was used to measure expression
      of uPA, uPAR, PAI-1, and PAI-2 proteins in 46 PC and 12 cystadenoma specimens.
      Results were related to survival using Cox's proportional hazards testing.
      RESULTS: Increased expression of uPA, uPAR, and PAI-1 in PC tissue were
      independently associated with a higher Union Internationale Contre le Cancer
      [International Union Against Cancer (UICC)] tumor stage (P < 0.001) and were
      intercorrelated (P < 0.001). Overexpression of uPAR indicated reduced survival (P
      = 0.03). Conversely, PAI-2 messenger ribonucleic acid (mRNA) overexpression,
      which occurred in 21 of 46 tumors, negatively correlated with tumor size (P =
      0.008) and survival (P < 0.007) but not with uPA, uPAR, or tumor stage. There was
      good agreement between PAI-2 mRNA value and IHC score (P < 0.001). Using Cox's
      stepwise analysis, PAI-2 mRNA value (HR = 0.24; P = 0.001) and UICC tumor stage
      (HR = 2.014; P = 0.001) independently predicted survival. An IHC score for PAI-2
      of 3+ or 4+ also independently predicted improved survival (HR = 2.72; P =
      0.025). CONCLUSIONS: The uPA/uPAR/PAI-1 system is activated in advanced
      pancreatic cancer and may account for the tumor's aggressive behavior, whereas
      PAI-2 expression appears to be independent of uPA/uPAR/PAI-1 and is associated
      with improved prognosis. Because of its intercorrelation with mRNA expression,
      PAI-2 IHC may be used as an indicator of survival.

PMID- 17219286
TI  - Critical appraisal on the role and outcome of emergency colectomy for
      uncomplicated right-sided colonic diverticulitis.
AB  - BACKGROUND: Emergency colectomy is well accepted for treating complicated right
      sided colonic diverticulitis. However, the role of colectomy for uncomplicated
      diverticulitis is not well defined. The aim of this study was to evaluate the
      short-term and long-term surgical outcome of uncomplicated right-sided
      diverticulitis in our locality. PATIENTS AND METHODS: Retrospective chart review
      of patients operated for right-sided diverticulitis over a 20-year period was
      conducted. Recurrent attacks of right-sided diverticulitis, re-operation rate and
      re-hospitalisation rate were the long-term parameters of interest. An updated
      telephone interview was carried out for all surviving patients. RESULTS: Seventy
      four patients (35 males and 39 females), median age 35.5 (range 16-70) years,
      were operated for uncomplicated diverticulitis. Thirty patients underwent
      colectomy, whereas the others underwent appendectomy with diverticulectomy (n =
      8) or appendectomy alone (n = 36). All short-term parameters were less favourable
      for the colectomy group, including higher complication rate, slower return of
      gastrointestinal function, higher requirement of parenteral analgesic and longer
      hospital stay. Without colectomy, only 2 patients developed recurrent
      diverticulitis necessitating hospitalisation, both of whom resolved on
      conservative treatment. On the other hand, 1 patient required re-operation after
      colectomy because of intestinal obstruction. The overall re-hospitalisation rate
      was comparable between the colectomy and the non-colectomy group (16.7% vs.
      13.6%). CONCLUSIONS: Emergency colectomy can eradicate suspicious lesions and
      eliminate risk of recurrent diverticulitis but at the expense of higher morbidity
      rates. As the natural course of uncomplicated right-sided colonic diverticulitis
      is usually benign, conservative treatment with minimal surgery may be a better
      therapeutic option.

PMID- 17219287
TI  - Impact of obesity on outcome and changes in quality of life after coronary artery
      bypass grafting.
AB  - BACKGROUND: An increasing proportion of patients undergoing coronary artery
      bypass grafting (CABG) are obese and are thought to carry a higher mortality and
      morbidity in association with surgery, but data on whether health-related quality
      of life (QOL) improves similarly after CABG in obese and non-obese patients are
      limited. We assessed in detail the effect of obesity on changes in health-related
      QOL (RAND-36 Health Survey) during the first year following CABG. METHODS:
      Comprehensive data on 508 CABG patients were prospectively collected. One hundred
      patients (19.7%) were categorized as obese (body mass index >or= 30 kg/m(2)). The
      RAND-36 Health Survey was used as an indicator of quality of life. Assessments
      were made preoperatively and repeated 12 months later. RESULTS: The obese group
      fared significantly worse than the non-obese group with regard to the likelihood
      of superficial wound infection (19.0% versus 7.1%, P < 0.001), impaired renal
      function (31.7% versus 14.4%, P = 0.01), and required on average 2 days longer in
      hospital (P < 0.05). The incidence of mediastinitis was not significantly higher
      among the obese patients (2.0% versus 1.2%, P = 0.55), and they less frequently
      needed postoperative red cell transfusions (29.0% versus 44.9%, P = 0.004). The
      obese improved significantly (P < 0.001) in 7, and the non-obese (P < 0.001) in
      all 8 RAND-36 dimensions. Physical Component Summary and Mental Component Summary
      scores on the RAND-36 improved significantly (P < 0.001) in obese as well as in
      non-obese patients. CONCLUSIONS: Although obese patients differ from non-obese
      patients in that they had inferior QOL before and in the year following CABG,
      they gain a similar improvement in QOL 1 year after surgery compared with non
      obese patients. Excluding superficial wound infection, transient impaired renal
      function, and slightly longer hospital stay, obesity does not significantly
      increase the risk of other adverse outcomes during the first year following CABG.

PMID- 17219288
TI  - Renal and perinephric abscesses: analysis of 65 consecutive cases.
AB  - OBJECTIVE: The objective was to describe the last 10 years' experience of the
      diagnosis and treatment of renal, perinephric, and mixed abscesses in an academic
      reference center. PATIENTS AND METHODS: The medical records of 65 patients with
      renal, perinephric, and mixed abscesses treated at our hospital from January 1992
      to December 2002 were reviewed. The data collected included predisposing factors,
      symptoms, physical examination, initial diagnosis, laboratory and radiologic
      evaluation, treatment, and clinical outcome. RESULTS: Perinephric abscesses were
      found in 33 (50.8%) patients, renal abscesses were found in 16 (24.6%), and 16
      (24.6%) had mixed abscesses. Urolithiasis (28%) and diabetes mellitus (28%) were
      the most common predisposing conditions. The duration of symptoms before hospital
      admission ranged from 2 to 180 days (mean 20 days). Urine culture was positive in
      43% of patients and blood culture was positive in 40% of patients. Most of the
      perinephric abscesses received an interventional treatment: surgical drainage
      (24%), percutaneous drainage (42%) or nephrectomy (24%). Most patients were cured
      (73.3%) on discharge from hospital. Mixed (renal and perinephric) abscess
      treatment was similar: percutaneous drainage (37.5%), surgical drainage (18.75%)
      or nephrectomy (37.5%). Most patients were cured (60%) on discharge from
      hospital. Renal abscesses, however, were treated medically in 69% of patients and
      73% were cured on discharge from hospital. CONCLUSIONS: Perinephric and mixed
      abscesses are successfully managed by interventional treatment. Renal abscesses
      can be managed by medical treatment only, reserving interventional treatment for
      large collections or patients with clinical impairment. Early diagnosis is an
      important factor in the outcome of renal and perinephric abscesses.

PMID- 17219289
TI  - Preoperative chemotherapy and the outcome of liver resection for colorectal
      metastases.
AB  - BACKGROUND: Neoadjuvant systemic chemotherapy is being increasingly used prior to
      liver resection for colorectal metastases. Oxaliplatin has been implicated in
      causing structural changes to the liver parenchyma, and such changes may increase
      the morbidity and mortality of surgery. PATIENTS AND METHODS: A retrospective
      study was undertaken of 101 consecutive patients who had undergone liver
      resection for colorectal metastases in two HPB centers. Preoperative demographic
      and premorbid data were gathered along with liver function tests and tumor
      markers. A subjective assessment of the surgical procedure was noted, and in
      hospital morbidity and mortality were calculated. The effect of preoperative
      chemotherapy on short-term and long-term outcome was analyzed, and actuarial 1
      and 3 year survival was determined. RESULTS: Patients who received neoadjuvant
      chemotherapy had a higher number of metastases (median 2, range 1-8 versus median
      1, range 1-5; P = 0.019) and more had synchronous tumors (24 patients versus 8; P
      < 0.001). Overall morbidity was 37% and hospital mortality was 3.9%. Operative
      and in-hospital outcome was not influenced by chemotherapy. Long-term survival
      was worse in patients who had received preoperative chemotherapy (actuarial 3
      year survival 62% versus 80%; P = 0.04). CONCLUSIONS: This study shows no
      evidence that neoadjuvant chemotherapy, and in particular oxaliplatin, increases
      the risk associated with liver resection for colorectal metastases. Long-term
      outcome is reduced in patients receiving preoperative chemotherapy, although they
      have more advanced disease.

PMID- 17219290
TI  - Method of biopsy and incidence of positive margins in primary melanoma.

PMID- 17219291
TI  - Laparoscopic parenchymal division of the liver in a porcine model: comparison of
      the efficacy and safety of three different techniques.
AB  - BACKGROUND: Bleeding is a known and CO2 embolization a suggested risk factor for
      increased morbidity after laparoscopic liver resection. Devices for laparoscopic
      liver parenchymal transection must be evaluated for safety in this context.
      METHOD: Twelve piglets underwent laparoscopic surgery during CO2
      pneumoperitoneum, each animal receiving three 6 cm long transections into the
      liver parenchyma made with ultrasonic dissector, ultrasonic shears and vessel
      sealing system, respectively. Endpoints were bleeding, operation time and gas
      embolization. The transections and embolization events, evaluated with
      transesophageal echocardiography, were video recorded. Bleeding and embolization
      were also assessed on video tapes and operating time measured. Arterial blood
      gases were recorded on line. RESULTS: The ultrasonic dissector was least
      advantageous in terms of bleeding and operation time. Gas embolization was more
      frequent with the vessel sealing system than with the ultrasonic dissector and
      ultrasonic shears. During two episodes of gas embolization, pCO2 increased and
      pO2 and pH decreased. CONCLUSIONS: Use of all three devices is feasible. Bleeding
      and operation time are greatest with the ultrasonic dissector. Gas embolization
      occurs during transection, though in most instances it is completely harmless.
      Laparoscopic liver surgery with these techniques used may pose a risk of gas
      embolization with clinical implications. Monitoring for such events is probably
      to be recommended.

PMID- 17219292
TI  - Effects of prior endoluminal gastroplication on subsequent laparoscopic Nissen
      fundoplication.
AB  - BACKGROUND: The long-term results of endoluminal gastroplication (ELGP) for
      gastroesophageal reflux disease (GERD) are still under investigation.
      Laparoscopic Nissen fundoplication (LNF) has unquestionable results in the
      treatment of GERD and, therefore, it would be unfortunate to compromise this
      treatment option by performing alternative therapies such as ELGP. METHODS: Six
      patients underwent ELGP for the treatment of GERD symptoms. After symptoms
      returned, these patients elected to have a LNF. RESULTS: There was no sign of
      periesophagitis or intraperitoneal adhesion formation found at hiatal dissection
      that hindered or complicated the LNF procedure. Recent follow-up has shown that
      the patient's GERD symptom scores have decreased, as expected after a de novo
      LNF. CONCLUSION: ELGP does not alter the surgical dissection or results of a
      subsequent LNF.

PMID- 17219293
TI  - Antifogging effects of a socket-type device with the superhydrophilic, titanium
      dioxide-coated glass for the laparoscope.
AB  - BACKGROUND: Lens fogging during laparoscopic surgery extensively deteriorates
      operative field visibility and may provoke serious complications. METHODS: A
      simulation model study was conducted using a conventional laparoscope, a
      conventional laparoscope plus heating (100 degrees C, 10 s), a conventional
      laparoscope plus surfactant, and a conventional laparoscope plus both a titanium
      dioxide (TiO2)-coated glass (with > or = 15 h of preoperative ultraviolet
      irradiation) and a water supply. For each, the time from laparoscope insertion
      into the peritoneal cavity to fogging-induced interruption of surgery was
      measured. RESULTS: The TiO2-coated glass had unique verified properties of
      exerting antifogging effects on the oil film after 15 or more hours of previous
      ultraviolet irradiation, and of inversely accelerating fogging after less than 15
      h of previous ultraviolet irradiation. The clinical study showed later fogging
      with the TiO2-coated glass model, which successfully completed surgery without
      retraction of the laparoscope from the peritoneal cavity, as compared with the
      other models. CONCLUSION: An antifogging device using superhydrophilic TiO2
      coated glass was very effective in preventing fogging during laparoscopic
      surgery.

PMID- 17219294
TI  - Heating and humidifying carbon dioxide is indicated.

PMID- 17219295
TI  - Evaluation of a fluorescent method for measuring cholinesterase activity in
      mammalian blood and tissue.

PMID- 17219296
TI  - Prediction of gas chromatographic retention indices of benzene dicarboxylic
      diesters using novel topological indices.

PMID- 17219297
TI  - Characterization of gas and particle emission from smoldering incenses with
      various diameters.

PMID- 17219298
TI  - Type and amount of asbestos in floor tile and mastic.

PMID- 17219299
TI  - Dissipation of chlorfenapyr residue in pakchoi and soil.

PMID- 17219300
TI  - Binding and water solubility enhancement of 14C-benzo[a]pyrene by dissolved
      organic matter in freshwater in Kenya.

PMID- 17219301
TI  - Removal of alachlor and pretilachlor by laboratory-synthesized zerovalent iron in
      pesticide formulation solution.

PMID- 17219302
TI  - Atmospheric dry deposition on leaves at an urban location.

PMID- 17219303
TI  - Distribution of epiphytic lichens and air pollution in the city of Trabzon,
      Turkey.

PMID- 17219304
TI  - Selective bioaccumulation of metals by different parts of some fish species from
      crude oil polluted water.

PMID- 17219305
TI  - Bioaccumulation of mercury in fish exposed to experimentally contaminated water
      and sediment.

PMID- 17219306
TI  - Effect of aerobic sludge with increasing level of adaptation on abietic acid
      biodegradation.

PMID- 17219307
TI  - Distribution and sources of polyaromatic hydrocarbons (PAHs) in surface sediments
      of Great Kwa River, Nigeria.

PMID- 17219308
TI  - Speciation distribution of lead and zinc in soil profiles of the Shenyang
      smeltery in Northeast China.

PMID- 17219309
TI  - Dehalogenation of lindane by Penicillium camemberti.

PMID- 17219310
TI  - White-tailed eagles (Haliaeetus albicilla) in Schleswig-Holstein no longer
      endangered by organochlorines.

PMID- 17219311
TI  - Effect of fungicide seed treatments on N2-fixation and nodulation in pea, Pisum
      sativum L.

PMID- 17219312
TI  - Toxicity assessment of contaminated sediments after dredging.

PMID- 17219313
TI  - Metals in shrimp farm sediments, Sinaloa, Northwest Mexico.

PMID- 17219314
TI  - Acute toxicity of the pesticides chlorpyrifos and atrazine to the Chinese mitten
      handed crab, Eriocheir sinensis.

PMID- 17219315
TI  - Immunological response of the freshwater fish Colossoma macropomum as a biomarker
      of copper exposure.

PMID- 17219316
TI  - Behavioral alterations in juvenile Cyprinus carpio (Linnaeus, 1758) exposed to
      sublethal waterborne cadmium.

PMID- 17219317
TI  - [Listing in the journal citation reports and impact factor--a milestone for the
      journal].

PMID- 17219318
TI  - [Apoptosis and its role in plastic surgery].
AB  - Apoptosis and cell proliferation are the main mechanisms of cell homeostasis. The
      pathogenesis of approximately 70 % of all diseases results from an imbalance
      between these two counterparts. Therefore, research on apoptosis is a main target
      in biological and clinical fields. Many signalling pathways and proteins involved
      in their regulation have been characterized. In order to evaluate the relevance
      of apoptosis in plastic surgery, the literature was reviewed for its impact on
      ischemia and reperfusion concerning flap surgery as well as wound healing and
      angiogenesis. Furthermore, the relevance of apoptosis in ageing,
      allotransplantation and tumors was investigated. In all subsections of plastic
      surgery, a high impact was identified. More studies on the influence and
      regulation of apoptosis can bring further understanding on the disease patterns
      of plastic surgery and other specialties as well as the development of new
      therapeutic options. Research focusing on apoptosis is therefore an essential
      means for the advancement of and future trends in plastic surgery.

PMID- 17219319
TI  - [Complications after dermal fillers and their treatment].
AB  - All dermal fillers are associated with the risk of both early and late
      complications. Early side effects such as swelling, redness, and bruising occur
      after intradermal or subdermal injections. The patient has to be aware of these
      risks and be prepared to accept them. Adverse events that last longer than 2
      weeks can be attributable to technical shortcomings (e.g., the implantation of a
      long-lasting filler substance was too superficial). Such adverse events can be
      treated with intradermal 5-fluorouracil and steroid injections, vascular lasers,
      or intense pulsed light, and later with dermabrasion or shaving. Late adverse
      events also include immunological phenomena such as late-onset allergy and non
      allergic foreign body granulomas. Both react well to intralesional steroid
      injections, which often have to be repeated to establish the right dose. Surgical
      excisions should remain the last option and are indicated for hard lumps in the
      lips and visible hard nodules or hard granulomas in the subcutaneous fat.

PMID- 17219320
TI  - [Anatomic considerations to improve vasculature of the nipple-areola complex in
      vertical mammaplasty].
AB  - AIM: This anatomic study is intended to point out the most regular and
      reproducible vessels supplying the nipple-areola complex (NAC) for use in
      vertical mammaplasty. BACKGROUND: The superior pedicle technique routinely
      performed within the context of vertical mammaplasty procedures bears some risk
      for vascular dependent complications of the NAC especially in large breasts.
      Concerning vasculature, the supposedly most eligible pedicle to use should meet
      equally the best vascular requirements and technical demands necessary for
      maintaining both viability of the NAC and plasticity of the entire breast tissue.
      METHODS: Based on an anatomic microdissection study of the thoracic vessel system
      of seven female corpses, a modification of the superior pedicle approach to carry
      the NAC was anatomically evaluated and tailored to vertical mammaplasty performed
      in the L-technique. RESULTS: Out of six vascular sources responsible for the
      blood supply to the breast the branches originating from the lateral thoracic
      artery and concomitant veins appeared to reflect the major source of blood supply
      to the NAC due to their regularity and reproducibility. Especially the full
      thickness glandular-dermal superolaterally-based pedicle should safely enclose
      these dominant branches, as well as supplementary vessels deriving from minor
      important sources in this region, while keeping plasticity of the vertically
      reduced breast. CONCLUSION: The superolaterally-based full-thickness glandular
      dermal pedicle mobilized epipectorally to carry the NAC proves to be anatomically
      a safe and reliable procedure eligible as an integral part of vertical
      mammaplasty.

PMID- 17219321
TI  - [Tissue engineering of peripheral nerves].
AB  - BACKGROUND: In spite of considerable progress in microsurgical techniques, the
      treatment of long distance defects in peripheral nerves remains challenging for
      the surgeon. Autologous nerve grafting has been the only applicable procedure to
      overcome such defects in the past. Due to the known disadvantages of this
      procedure (neuroma formation and sensory deficits at the donor-site, limited
      availability of donor-material, etc.) and impaired regenerative results,
      different tubulisation techniques are discussed more frequently as alternatives
      to the autologous nerve grafts. AIM OF THE STUDY: In this work, the authors
      summarise their experiences and results with different synthetically developed
      materials, cellular and acellular tubes and venous conduits for the
      reconstruction of peripheral nerve defects. MATERIAL AND METHODS: To analyse
      peripheral nerve regeneration, we utilised a median nerve model in rats. In these
      studies nerve gaps up to 40 mm were induced. Guiding tubes of various materials
      (trimethylene carbonate-epsilon-caprolactone, polyethylene, veins, and collagen)
      were employed. Furthermore, we introduced Schwann cells as cellular elements into
      some of the trimethylene carbonate-epsilon-caprolactone tubes. The longest
      postoperative observation period was nine months. RESULTS: The results
      demonstrated that only in the case of cellular filled tubes (syngenic Schwann
      cells) did regeneration occur across the 20 mm gap. This regeneration was
      comparable to that induced after autologous grafting. Across a 40 mm gap the
      autologous graft demonstrated the best results.

PMID- 17219322
TI  - [The infragluteal perforator flap].
AB  - PURPOSE: Pressure sores of the ischial tuberosities are mostly covered with
      fascio- or myocutaneous flaps of the posterior thigh. In doing so, vascular
      territories of adjacent flaps are violated, which are not available any more in
      case of ulcer recurrences. In consideration of the high recurrence rates of
      pressure sores in paraplegics, we developed an infragluteal perforator flap that
      spares adjacent vascular territories. PATIENTS/MATERIAL AND METHOD: Infragluteal
      perforator flaps were dissected in five fresh human cadavers to investigate the
      anatomic relations of the cutaneous branches of the inferior gluteal artery and
      the inferior clunial nerves and to define the anatomic landmarks for clinical
      application of an innervated flap. In six paraplegic patients with primary (5/6)
      and secondary (1/6) pressure sores of the ischial tuberosity, infragluteal
      perforator flaps were used for wound coverage. The donor defect was closed
      primarily and postoperative care and patient mobilisation followed a standardised
      protocol. RESULTS: In eleven infragluteal perforator flaps that were dissected in
      cadavers and patients, we found one or two cutaneous branches of the descending
      branch of the inferior gluteal artery at the lower border of the gluteus maximus
      muscle that supplied the infragluteal skin. Infragluteal perforator flaps could
      be harvested on these perforator vessels and transferred to the ischial defects
      without tension due to the excellent mobility of the skin island. The descending
      branch of the inferior gluteal artery could be spared in all cases for future
      flaps. In one patient with multiple recurrences of an ischial pressure sore flap
      necrosis occurred due to venous congestion. The other five infragluteal
      perforator flaps healed without complications. CONCLUSION: The infragluteal
      perforator flap is suitable for the closure of pressure sores of the ischial
      tuberosities and can be used as a sensitised flap by inclusion of the inferior
      clunial nerves. Compared to traditional pedicled flaps of the posterior thigh,
      the infragluteal perforator flap reduces donor site morbidity and spares the
      vascular territories of adjacent flaps for future recurrent ulcers.

PMID- 17219323
TI  - [Oropharyngeal reconstruction with a free jejunum graft after tumour and stenosis
      resection: an analysis of 53 cases].
AB  - The surgical therapy of oropharyngeal carcinoma by means of a free jejunum graft
      is an established procedure. The application of a monitor segment for
      postoperative flow control turned out to be a reasonable modification. In this
      study, we examine the results over a period of 16 years retrospectively. Between
      1988 and 2004, 53 patients underwent oropharyngeal reconstructions by means of 58
      free jejunum grafts at the clinic for reconstructive surgery in cooperation with
      the clinic for otorhinolaryngology. All patients were examined postoperatively
      with the help of a small jejunum loop in the function of a monitor segment to
      survey flap vitality. Between the 7th and 11th postoperative day the patients
      were administered Gastrografin to evaluate oesophagojejunal anastomoses. The
      survival ratio of the transplants in this series amounted to 90.6 %. All
      anastomoses were initially passable and leak-proof. After a complete loss of the
      first graft, five patients were successfully reconstructed with a second jejunum
      graft. In one patient, the vessel anastomoses had to be revised. In two patients,
      newly formed stenoses were postoperatively treated with a bougie during
      hospitalisation. In four patients, fistula formation was detected in the follow
      up examination. Substantial advantages of the free jejunum graft compared to
      other alternative free or local tissue transfers are the excellent functional
      results, the simple local tumour monitoring and the low complication rate.

PMID- 17219324
TI  - [Clinical impact of operative multidisciplinarity for severe defect injuries of
      the lower extremity].
AB  - BACKGROUND: The aim of this study was to examine the impact of our
      multidisciplinary therapeutical concept (MTC) on the clinical outcome in
      posttraumatic defect injuries of the lower extremity. PATIENTS AND METHODS: Since
      1999, we have performed a free tissue transfer in 37 patients. In group 1 (n =
      21), our MTC was started more than two weeks (range: 17 to 83 days) after trauma
      and in group 2 (n = 16) within two weeks (range: four to twelve days) after
      trauma. Both groups were comparable with respect to trauma severity. RESULTS: 100
      % patients of group 1 and 25 % patients of group 2 had clinical and
      microbiological manifestations of wound infection after admission in our clinic.
      Significantly more operations were necessary in group 1 compared to group 2 (7.3
      +/- 2.6 versus 2.9 +/- 0.8; p < 0.05), until definitive wound closure could be
      achieved. The postoperative course was uneventful in 35 cases. All injured
      extremities could be salvaged. Multistaged bone reconstructions by means of
      spongious or tricortical bone from the iliac crest were successful in all cases.
      Hospital stay after admission to our clinic was significantly longer in group 1
      compared to group 2 (57 +/- 12 days versus 31 +/- 7 days, p < 0.05). CONCLUSIONS:
      In our study, the early start of MTC significantly reduced the risk for wound
      infection, the number of surgical revisions before definite wound closure and
      time until bone and wound healing was completed.

PMID- 17219325
TI  - [Patients' satisfaction and social reintegration after breast reconstruction with
      the DIEP/TRAM flap].
AB  - The aim of the study was to evaluate social reintegration and patients'
      perception after breast reconstruction with the free TRAM/DIEP flap. Between 2004
      and 2006, 100 patients with an average age of 48 years with breast cancer,
      capsular contracture and lymphangioma underwent single or second stage autologous
      tissue transfer. In 7 patients reconstruction was performed on both sides
      (altogether 107 flaps). The patients were seen for postoperative evaluation and
      were asked for their personal acceptance after reconstruction. Postoperatively,
      no instability of the abdominal wall was seen. 3 patients had a total flap loss,
      in 2 patients a partial loss was evident, 1 had a hematoma, 2 showed successfully
      treated thrombosis of the flap vein, and 2 patients suffered from wound healing
      problems at the flap and 4 patients at the abdomen. Aesthetic results concerning
      natural feeling and breast symmetry were graded as excellent and patients'
      satisfaction was high.

PMID- 17219326
TI  - [Commentary on the article of V. L. Moser et al.: Is a differentiated treatment
      depending on the degree of severity justified in cubital tunnel syndrome?
      Handchir Mikrochir Plast Chir 2006; 38: 172-177].

PMID- 17219327
TI  - [Commentary on the article of V. L. Moser et al.: Is a differentiated treatment
      depending on the degree of severity justified in cubital tunnel syndrome?
      Handchir Mikrochir Plast Chir 2006; 38: 172-177].

PMID- 17219328
TI  - [Commentary on the article of V. L. Moser et al.: Is a differentiated treatment
      depending on the degree of severity justified in cubital tunnel syndrome?
      Handchir Mikrochir Plast Chir 2006; 38: 172-177].

PMID- 17219330
TI  - [Current status of head and neck cancer therapy in the elderly].
AB  - In the years to come health care systems of western industrialized nations are
      going to be increasingly faced with the results of demographic changes.
      Especially the part of elderly citizens will grow steadily. Thus, also an
      increasing number of malignant diseases not only in the head & neck area is
      expected. Decision-making in cancer therapy for elderly patients is challenging
      for medical professional since this subject is accompanied by a high rate of
      uncertainness. For fear of aggressive therapy regimens with subsequent increase
      of morbidity, in many cases only incomplete diagnostic and therapeutic measures
      are taken. Reviewing the literature there is almost complete international
      consensus, that patients suffering from squamous cell cancer of the head & neck
      should be treated with curative intention, if thorough preoperative assessment of
      present comorbidities is performed. Furthermore aggressive treatment options
      should not be excluded. An optimal medical adjustment of relevant concomitant
      diseases clearly improves the starting point. In comparison to younger control
      groups therapy associated complications do not occur significantly higher. For
      this reason elderly patients should be treated with curative intention. Age
      itself should never be a sole factor deciding which curative therapy should be
      undertaken. Exceptions could be made in patients with severe general comorbidity.

PMID- 17219331
TI  - [Results after lidloading with rigid gold weights--a meta-analysis].
AB  - INTRODUCTION: For the surgical therapy of lagophthalmos rigid gold implants were
      used. There are a lot of studies using rigid gold implants with widely different
      complications. In the primary study the small amount of patients is often a
      problem. The aim of our study was to survey the postoperative results and
      complications after insertion of rigid gold implants and to statistically compare
      the results with a meta-analysis. MATERIAL AND METHODS: 38 publications on 1000
      rigid gold implants were analyzed in the context of a meta-analysis of the
      postoperative results. RESULTS: Complete lid closure can be obtained in 84.5 %
      with the rigid gold implants. The postoperative complication rates were 13.4 %
      for bulging, 6.4 % for migration, 6.8 % for extrusion, 11.5 % for corneal
      astigmatism and 7.0 % postoperative infections. DISCUSSION: Lidloading is a very
      simple and reversible procedure for the surgical treatment of lagophthalmos. The
      statistical analysis in using rigid gold implants showed a significant rate of
      postoperative complications. To increase the effectivity of the treatment method
      these results should be taken into account for alternative implants.

PMID- 17219332
TI  - [Conventional tomographic investigations of the reconstructed middle ear in
      temporal bone specimen].
AB  - BACKGROUND: In modern reconstructive middle ear surgery imaging plays an
      essential role as a diagnostic tool, especially in pre-operative planning.
      Nowadays imaging of surgical results as a matter of quality control in post
      operative follow-up becomes more important. MATERIAL AND METHODS: Conventional
      tomography was performed in 10 temporal bone specimen using the CommCat IS 2000
      system in order to evaluate anatomical structures and inserted middle ear
      prostheses (PORP/TORP). This imaging technique has not been used in middle ear
      surgery beforehand. RESULTS: Using conventional tomography characterization of
      anatomical structures of the temporal bone as e. g. the semicircular canals
      appeared to be of superior quality to comparable conventional radiographic
      imaging. Concerning imaging quality (contrast; resolution) conventional
      tomography allowed similar findings like computed tomography (CT)-scans in some
      of the investigated specimen while showing inferior sharpness quality due to
      technical reasons. Further advantages of conventional tomography in contrast to
      CT were the requirement of just 2.5 % of the CT's irradiation exposure, lack of
      metallic artefacts caused by implanted prostheses and the feasibility of distance
      and angle-measurement of inserted prostheses towards the tympanic membrane which
      coincided extensively with the temporal bone preparation. CONCLUSIONS:
      Conventional tomography enables detailed anatomical imaging of the temporal bone
      region which outperforms conventional radiographic imaging, requires less
      irradiation dose than CT and helps avoid problems like metallic artefacts. This
      technique enhances immediate quality-control and seems to be therefore a
      promising tool for postoperative evaluation after reconstructive middle ear
      surgery.

PMID- 17219333
TI  - [Glottal and supraglottal configuration during whispering].
AB  - BACKGROUND: The purpose of the study was to assess glottal and supraglottal
      configurations during whispering in comparison to habitual phonation and to
      visually estimate to what extent force is exerted onto the vocal fold epithelium
      during whispering. Is whispering a good compromise between preservation of
      epithelium and permission to communicate orally, e. g. postoperatively? PATIENTS
      AND METHODS: We investigated on 100 patients with organic or non-organic voice
      disorders. Patients with vocal fold immobility and patients with organic lesions
      large enough to impede glottal closure were excluded. Videolaryngoscopy and
      stroboscopy was performed via flexible endoscopy. During fiberoscopy the patients
      were asked (i) to phonate and then whisper a series of vowels in various loudness
      levels and (ii) to count to 10 voiced and whispered in various loudness levels.
      The extent of vocal fold adduction and supraglottal configuration were assessed
      and whispering compared with voiced phonation. RESULTS: Interindividual
      differences in glottal and supraglottal configuration during whispering were
      seen. The two different and most frequently seen glottal area patterns were
      determined by the position of the vocal processes - either adducted or abducted.
      Adduction resulted in sole cartilaginous triangle formation or 'kissing
      processes', abduction in ligamentous and cartilaginous triangle. Another
      surprising result was that with increasing loudness either a narrowing or
      widening of glottal and supraglottal structures was visible. CONCLUSIONS: There
      are different patterns of glottal and supraglottal configuration during
      whispering. Although the vocal folds can show partial or total contact over the
      membranous parts, the lack of additional vibration of the vocal folds suggests
      that epithelial forces are smaller than with additional vibratory shear stress.
      Thus, whispering may be considered and allowed for postoperative communication
      purposes, when patients follow instructions for low-effort whispering.

PMID- 17219334
TI  - [Wegener's granulomatosis and orbital complications of sino-nasal origin].
AB  - Wegener's granulomatosis is an idiopathic, granulomatous disease with the
      potential for multiple head and neck manifestations (80 % of the patients).
      Sinonasal symptoms are observed in more than 60 % of the patients. Due to these
      facts the otorhinolaryngologist plays an essential role in the multidisciplinary
      team involved in establishing the diagnosis early, initiating immunosuppressive
      therapy and providing ongoing care. The treatment is based on medical therapy
      consisting of corticosteroids and immunosuppressive agents, whereas surgery is
      reserved for selected head and neck manifestations. By means of 3 patients
      presenting with distinct visual loss in consequence of orbital complications with
      sinonasal origin the course of disease and theoretical background are reviewed.
      In our patients Wegener's granulomatosis was diagnosed by histopathological
      examination and serological detection of ANCA, cANCA. The progression of the
      granulomatous process and an additional purulent inflammation in 2 cases led to a
      temporary amaurosis and in another case to a visual loss of 50 %. Immediate
      orbital decompression in combination with sufficient systemic immunosuppressive
      treatment relieved the compression of the optical nerve and preserved vision. We
      conclude that early orbital decompression either by external or endonasal
      approach and concomitant immunosuppression is necessary to determine or improve
      rapidly decreasing vision subsequent to high intraorbital pressure produced by a
      granulomatous process and inflammation.

PMID- 17219335
TI  - [High duplication of an internal jugular vein].
AB  - The internal jugular vein is an important landmark in most cervical operations.
      The surgeon should know the exact position and possible variations to prevent
      complications. We report on a duplicated internal jugular vein, which is a rare
      anatomic anomaly and discuss aetiology and appearance of this malformation and
      the possible affecting of the accessory nerve.

PMID- 17219336
TI  - [Recurrent facial paresis with facial neurinoma].
AB  - PATIENT: A clinical case of a 49-year-old man is described who presented with a
      right facial paresis for 4 weeks. The patient had undergone a decompression of
      facial nerve and a radical mastoidectomy elsewhere in 1998 because of a facial
      paresis and acute mastoiditis. In the following years a complete right facial
      paresis occurred several times improving with prednisolone. In addition to
      topognostic examinations a high resolution computed tomography of the temporal
      bone was made. CT showed a mass in the right tympanic cavity with close contact
      to the ossicular chain. Diagnostic tympanotomy disclosed a tumor of the tympanic
      segment of the facial nerve. Pathological examination indicated a diagnosis of
      neurinoma with an Antoni B architecture. In a second operation the tumor was
      resected totally and a facial nerve reconstruction was performed by a greater
      auricular nerve interposition graft. Seven month postoperative beginning nerve
      reinnervation was seen proceeding continually until the control examination after
      1 1/2 year. DISCUSSION: Facial neurinoma are a rare course of facial paresis.
      There are no specific symptoms. That's why the diagnosis is difficult. But it is
      necessary to think of with differential diagnosis of facial paresis.

PMID- 17219337
TI  - [Desmoid tumors of the head and neck].
AB  - Desmoid tumors of the head and neck, also known as aggressive fibromatoses, are
      rare. They are soft tissue neoplasms arising from musculoaponeurotic structures
      and characterized of locally aggressive infiltration and recurrences. Complete
      surgical excision of desmoid tumors is considered to be the only effective method
      of cure. It is likewise important to make a function-preserving surgery. In
      addition to the radicality this aspect should be a primary goal to minimize
      morbidity. MRI is the first choice in the preoperative evaluation of neck
      desmoids. We describe the successful treatment of desmoid tumors in two cases (M.
      sternocleidomastoideus, M. levator scapulae). Intraoperative neuromonitoring was
      very helpful for identification and protection of the motor nerves.

PMID- 17219338
TI  - [Multiple primary pleomorphic adenomas of the unilateral parotid gland].
AB  - BACKGROUND: Classical lateral parotidectomy is the standard surgical procedure
      for the management of lateral lobe parotid pleomorphic adenomas in most clinical
      centres. Extracapsular dissection and subtotal lateral parotidectomy are
      alternatively discussed in current literature and preferred by many authors.
      CASE: We report on a 20-year-old patient with multiple primary pleomorphic
      adenomas in the unilateral parotid gland, which preoperatively presented as a
      solitary tumour node. CONCLUSION: Considering this case we focus on the
      distinctive surgical procedures for the management of parotid pleomorphic
      adenomas. We work out, why lateral or even total parotidectomy are justified in
      the treatment of solitary palpable tumours and why we account lateral
      parotidectomy as the standard surgical procedure for the management of lateral
      lobe parotid pleomorphic adenomas.

PMID- 17219339
TI  - [Otogenic cerebellar abscess - two case histories].
AB  - OBJECTIVE: The otogenic brain abscess remains a serious intracranial complication
      of otitis media despite advantages in diagnostics and antibiotic treatment during
      the last decades. We discuss the clinical picture and the possible ways of
      treatment by the example of two case histories. CASE HISTORIES: Case 1: We report
      about a 38-year-old man, who was suffering in cholsteatoma since 30 years. The
      surgical revision was restricted by the patient since this time. The acute
      symptoms of meningitis were caused by intracranial involvement and cerebellar
      abscess due to cholesteatoma. After surgical revision we observed a period of
      clinical improvement. A repeated surgery became necessary because of renewed
      brain abscess at the cerebellar region five weeks after primary operation. Case
      2: A 6-year-old girl was already treated with antibiotics because of subacute
      mastoiditis since three weeks. She was entering the ENT department because of
      headache and otorrhoea. During mastoidectomy the bone destruction leads to a
      cerebellar abscess. The neurological symptoms were regredient immediately after
      the surgical revision. CONCLUSION: Both case histories underline the importance
      of cerebellar abscess as an intracranial complication of chronic otitis media.
      The neurologic symptoms and the CT-scan were essential for the exact diagnosis.
      The following treatment includes the surgical revision of the middle ear, the
      abscess-drainage as well as the lavage of the cavity with antibiotics.

PMID- 17219340
TI  - [Effect of candesartan cilexetil with hydrochlorothiazide on blood pressure and
      ST-segment depression in patients with arterial hypertension].
AB  - OBJECTIVE: To examine the effect of candesartan cilexetil with
      hydrochlorothiazide (6 mg and 12.5 mg, respectively) on blood pressure and ST
      segment depression during daily life of patients with treated but not controlled
      arterial hypertension (blood pressure taken at doctor's practice (3)140/90 mmHg,
      despite being on at least two antihypertensive drugs) PATIENTS AND METHODS: 51
      patients (45 men, 17 women) with treated but reportedly uncontrolled hypertension
      were placed on self-measurement of blood pressure for 4 weeks of a run-in period
      and 8 weeks as a follow-up period. Combined 24-hour automatic blood pressure
      measurement (ABPM) and electrocardiography were done at the end of the run-in and
      the follow-up periods. Ten patients proved to be normotensive according to the
      self-measurement and ABPM after the run-in period (group A), while 41 were still
      uncontrolled according to both methods (group B). In group B the least
      efficacious component of the antihypertensive medication was replaced by
      candesartan with hydrochlorothiazide (C + HCT) and any changes in blood pressure
      and ST-segment depression analysed after 8 weeks of follow-up in both groups.
      RESULTS: In group A no significant blood pressure change was observed between run
      in- and follow-up periods. But in group B (n=41) the self-measured systolic blood
      pressure had significantly decreased (155/84 mmHg compared with [vs] 147/81 mmHg;
      p<0.0073) as had the systolic 24-h ABPM (148/81 mmHg vs 137/753 mmHg; p<0.0015)
      after C + HCT had replaced the previous noneffective medication. After the run-in
      period 15 patients of group B had ST-segment depression (1 mm of horizontal or
      descending depression for at least 1 minute). In 16 other patients of group B and
      in all patients of group A no ST depressions were recorded. At the end of the
      follow-up period significant reduction of mean ischemic burden per patient (106
      vs 72 minutes), of total ischemic events (228 vs 153) and of mean duration of ST
      depression (372 vs 210 seconds) had occurred. CONCLUSIONS: Replacing candesartan
      + hydrochlorothiazide for previously ineffective antihypertensive drugs in
      patients with uncontrolled arterial hypertension significantly reduced both blood
      pressure and ST-segment depression during daily life.

PMID- 17219341
TI  - [The "broken heart" syndrome--a rare clinical phenomenon].
AB  - BACKGROUND AND OBJECTIVE: A clinical entity that mimics acute coronary syndrome
      with reversible left ventricular systolic dysfunction and is triggered by
      emotional stress was identified in 6 patients by screening a database of > 1000
      patients with the ICD-10 coding of acute coronary syndrome. The search criteria
      were acute coronary syndrome, normal coronary anatomy, absence of coronary
      lesions and transient left ventricular dysfunction, triggered by emotional
      stress. PATIENTS AND METHODS: We analyzed 6 patients, who fulfilled the criteria
      of (1) acute substernal chest pain with ST-segment elevation and/or T-wave
      inversion; (2) absence of significant coronary arterial narrowing on angiography,
      (3) systolic dysfunction with abnormal regional wall motion ("apical ballooning")
      in the context of (4) severe psychological stress immediately before and
      triggering the cardiac events. RESULTS: The primary diagnosis for all 6 acutely
      ill patients accorded with the ICD-code of acute coronary syndrome. All patients
      had survived and eventually recovered with an LV ejection fraction of 60 +/- 5 %;
      P = 0.03 and had had recovered normal levels of physical activity at hospital
      discharge. Of note is the number of women of postmenopausal age. CONCLUSIONS: A
      transient cardiomyopathy triggered by major emotional stress may mimic an acute
      coronary syndrome but without significant coronary artery disease. This condition
      is characterized by reversible cardiac dysfunction and may be more frequent in
      women. It has a favorable clinical outcome.

PMID- 17219342
TI  - [Werner's syndrome].
AB  - HISTORY AND CLINICAL FINDINGS: A 49-year-old man of German parentage with
      Werner's syndrome (including insulin-dependent type 2 diabetes mellitus) was
      treated in our department for extensive ulcers on his lower legs. GENETICS:
      Genetic analysis detected a novel compound heterozygous defect (1396delA and
      2334delAC) of the WRN gene. TREATMENT AND FURTHER COURSE: The ulcer clearly
      decreased in size on local and antibiotic treatment as well as autologous
      fibroplast transplantation. The most severely affected right small finger
      required amputation with exarticulation. The severe pain caused by the ulcer was
      successfully treated with temporary blockage of the stellate ganglion and
      permanent sympathetic blockage at the level of the 2nd thoracic and lumbar
      vertebrae. CONCLUSION: Werner's syndrome is a rare form of progeria with an
      autosomal recessive mode of inheritance mimicking the symptoms of accelerated
      aging. The reduced life expectancy is caused by the increased incidence and early
      onset of atherosclerosis and malignant tumors. The detection of underlying
      molecular mechanisms will have an important impact in the field of anti-aging
      research.

PMID- 17219343
TI  - [Reactivation of varicella-zoster-virus in the area of the left vagus nerve
      (herpes zoster)].

PMID- 17219344
TI  - [Reconstructive techniques for valvular heart disease].

PMID- 17219345
TI  - [Pulmonary hypertension in sickle cell disease--epidemiology, pathogenesis,
      diagnosis and treatment].

PMID- 17219346
TI  - [The 12th German Drug Law (AMG) amendment: an obstruction for non-commercial
      clinical trials?].

PMID- 17219347
TI  - The interplay between behavior and morphology in the evolutionary dynamics of
      resource specialization.
AB  - We analyze the consequences of diet choice behavior for the evolutionary dynamics
      of foraging traits by means of a mathematical model. The model is characterized
      by the following features. Consumers feed on two different substitutable
      resources that are distributed in a fine-grained manner. On encounter with a
      resource item, consumers decide whether to attack it so as to maximize their
      energy intake. Simultaneously, evolutionary change occurs in morphological traits
      involved in the foraging process. The assumption here is that evolution is
      constrained by a trade-off in the consumer's ability to forage on the alternative
      resources. The model predicts that flexible diet choice behavior can guide the
      direction of evolutionary change and mediate coexistence of different consumer
      types. Such polymorphisms can evolve from a monomorphic population at
      evolutionary branching points and also at points where a small genetic change in
      a trait can provoke a sharp instantaneous and nongenetic change in choice
      behavior. In the case of weak trade-offs, the evolutionary dynamics of a
      dimorphic consumer population can lead to alternative evolutionarily stable
      communities. The robustness of these predictions is checked with individual-based
      simulations and by relaxing the assumption of optimally foraging consumers.

PMID- 17219348
TI  - Nexialism and translational research.

PMID- 17219349
TI  - Evaluation of the PRISMA M10 circuit in critically ill infants with acute kidney
      injury: A report from the Prospective Pediatric CRRT Registry Group.
AB  - Currently available extracorporeal circuits in the US often require blood priming
      to prevent hypotension/anemia in smaller pediatric patients. The PRISMA M10
      circuit, available in other countries has not received extensive study and has
      not been cleared for use in the US. We performed an FDA mandated study of the M10
      circuit in the US for use in critically ill pediatric patients with acute kidney
      injury <15 kg in size. FDA guidelines allowed for maximal blood pump flow of 20
      ml/min. Fifteen pts (9 M, 6 F, mean size 5.8+/-2.8 kg, range 2.6-12.5 kg, age 4 d
      - 13 mo, mean creatinine =1.2+/-0.7 mg/dL) were studied at 4 ppCRRT centers.
      Sixty-one filters (range 1-4 circuits per pt) were used (mean circuit life 28.6+/
      22.5 h, range 1 to 74.5 h, 55%>24 h). No blood leaks occurred. All circuits
      achieved Qb 20 ml/min. Forty-two out of 61 filters clotted and mean circuit life
      was lower for these filters than those changed for other reasons (23+/-17 vs.
      41+/-28 h, <0.005). Circuits using larger access demonstrated significantly
      longer survival. We conclude that the M10 filter can serve well for CRRT in small
      pediatric patients. Further study is needed to determine in higher blood flow
      rates would decrease clotting rates and increase filter life span and
      ultrafiltration rates.

PMID- 17219350
TI  - Long-term peritoneal dialysis experience in Portugal.
AB  - Peritoneal dialysis (PD) penetration varies widely. Since the beginning of this
      therapy, indications have changed and outcomes have improved. In Portugal, PD
      still remains clearly underutilized. The results of a 20 year PD programme were
      evaluated: 312 cumulative patients, 48+/-16 years, 27%>60 years old, 27%
      diabetic, 59% with prior hemodialysis (HD). The main reason for admission was
      vascular access failure (48.7%). Admission due to patient preference has
      increased significantly between first and second decades of the programme (33% vs
      47% (P<0.001)); 98 patients (31.4%) were treated with automated PD but this
      prescription increased to 43% of the active patients.A total of 376 Tenckhoff
      catheters were surgically implanted, recently by the Popovich-Moncrief technique
      (77 catheters): the cumulative survival was 82%, 64% and 50% at 1, 3 and 5
      years,respectively. A better catheter survival was found in the last decade
      (85.7%, 69.6%, 54.8% versus 77.3%, 55.5%, 40.2%, at 1, 3 and 5 years,
      respectively (P=0.007). The patient and technique cumulative survivals were 91,
      74, 55% and 85, 67, 41%, at 1, 3, and 5 years, respectively. The main drop-out
      was to hemodialysis (35.8%), followed by death (23.7%), and transplantation
      (21.5%). Peritonitis and access-related infections caused 35% of the transfer to
      HD. Cardiovascular events caused 58% of deaths. The median PD retention was 35.5
      months. The rate of peritonitis has decreased to one episode /30 patient months.
      Hospital admission has also decreased to 4.8 days/patient year. This is a first
      report on long-term PD experience in Portugal. It has been an effective modality
      of renal replacement therapy, reflected by the growing patient preference in our
      PD programme.Experience, knowledge and new technical solutions have improved the
      outcomes.

PMID- 17219352
TI  - Autopsy findings in patients on postcardiotomy extracorporeal membrane
      oxygenation (ECMO).
AB  - OBJECTIVES: To assess the clinical sensitivity of causes of death, concomitant
      diseases and postoperative complications including thromboembolic events in ECMO
      patients. METHODS: Between January 2000 and December 2004 154/202 patients
      (76.2%) died after postcardiotomy ECMO circulatory support. Autopsy was performed
      in 78 (50.6%) consecutive patients. Clinical and post-mortem data were
      prospectively recorded and compared concerning causes of death and postoperative
      complications including venous and arterial thromboembolisms and significant
      comorbidities. RESULTS: Mean age was 62.1+/-11.3 years, ejection fraction was
      43.4+/-17.3%. 39.7% were emergency operations including acute coronary syndrome
      in 25.6% and preoperative cardiogenic shock in 28.2%. Successful ECMO weaning
      rate was 43.6%. Mean postoperative survival was 11.3 days. Premortem unknown
      concomitant diseases were found in 63 patients (80.8%) with clinical relevance in
      9 patients (11.5%). Clinically unrecognized postoperative complications were
      found in 59 patients (75.6%) including acute cerebral infarction (n=7), acute
      bowel ischemia (1), intestinal perforation (3), pneumonia (4), venous thrombus
      formation (25) and systemic thromboembolic events (24). Clinically based causes
      of death were cardiac in 62.8%, multi-organ failure in 10.3%, cerebral in 5.1%,
      respiratory in 10.3%, fatal pulmonary embolism in 2.6%, technical in 5.1%, and
      others in 3.8%. Unexpected causes of death were found by autopsy in 22 patients
      (28.2%) including myocardial infarction (n=5), acute heart failure (4), fatal
      pulmonary embolism (2), pneumonia (2), ARDS (1), lung bleeding (1), fatal
      cerebrovascular event (4) and multiorgan failure (3). CONCLUSIONS: In ECMO
      patients major discrepancies between clinical and post-mortem examination were
      found. The true incidence of thromboembolic events is highly underestimated by
      clinical evaluation.

PMID- 17219351
TI  - Microcirculation as a novel marker of membrane biocompatibility.
AB  - BACKGROUND: It is possible to consider microcirculation as a kind of OwitnessO of
      the complex biological reactions triggered by the dialytic treatment. The
      reactivity of microcirculation to the dialytic stress may represent a measure of
      the overall biocompatibility of the membrane. In this study we tested the
      hypothesis that different synthetic membranes may have different biological
      effects, particularly related to microcirculation. SUBJECTS AND METHODS: In this
      crossover study, we observed 16 chronically hemodialyzed patients. All patients
      were treated with the EVAL membrane; we recorded the TcPO2 during the second
      treatment of the week. All patients were then switched to the hf-PS membrane.
      During the study observation we did not change the dialytic prescription or the
      pharmacologic treatment. RESULTS: From the beginning of the session until 90O,
      the behavior of TcPO2 is similar for both the membranes. From 120O to the end of
      the treatment in sessions with the EVAL membrane, the TcPO2 values come back to
      the starting level, whereas in the treatments with hf-PS the TcPO2, the values
      remain at a lower level; there was a significant difference between EVAL and hf
      PS in the values recorded. Arterial blood gas values of paO2 and paCO2 are quite
      similar in the treatments with both the membranes, without any significant
      difference. CONCLUSIONS: The analysis of microcirculation by means of TcPO2
      measurement is a useful tool to obtain a OclinicalO measure of biocompatibility
      of the dialytic treatment and different membranes may have different impacts on
      TcPO2.

PMID- 17219353
TI  - CFD simulation of a novel bileaflet mechanical heart valve prosthesis: an
      estimation of the Venturi passage formed by the leaflets.
AB  - The aim of this study was to validate the flow characteristics of the novel
      Helmholtz-Institute Aachen Bileaflet (HIA-BL) heart valve prosthesis. The curved
      leaflets of the HIA-BL valve form a Venturi passage between the leaflets at peak
      systole. By narrowing the cross section the flow accelerates and the static
      pressure at the central passage decreases according to the Venturi effect. The
      low-pressure zone between the leaflets is expected to stabilize the leaflets in
      fully open position at peak systole. To investigate the Venturi passage, the flow
      fields of two valve geometries were investigated by CFD (Computational Fluid
      Dynamics): one geometry exhibits curved leaflets resulting in a Venturi passage;
      the other geometry features straight leaflets. The flow profiles, pressure
      distribution and resulting torque of both passages were compared and
      investigated. Although flow profiles downstream of both valves were similar, the
      flow passages between the leaflets were different for the investigated leaflet
      geometries. The straight leaflet passage showed a large boundary layer separation
      zone near the leaflets and the lowest pressure at the leading edge of the
      leaflet. The Venturi passage showed a reduction of the boundary layer separation
      zones and the lowest pressure between the leaflets could be found in the
      narrowest flow cross section of the Venturi passage. Additionally, the resulting
      torque showed that the Venturi passage produced an opening momentum. The results
      demonstrate that the Venturi passage stabilizes the leaflets in open position at
      peak systole.

PMID- 17219354
TI  - Comparison of specific adsorbents for tumor necrosis factor-alpha and therapeutic
      anti-tumor necrosis factor-alpha antibodies: an in vitro sepsis model.
AB  - BACKGROUND: Tumor necrosis factor alpha (TNF-alpha), as a key mediator,
      represents a major point of attack in sepsis. Since it has been shown that
      systemic anti-TNF-alpha antibodies do not improve the situation of septic
      patients, the use of specific adsorption technology in the treatment of sepsis
      could have beneficial effects. METHODS: Magnetic beads coated with polyclonal or
      with monoclonal anti-TNF-alpha antibodies were investigated in vitro in order to
      analyze their ability to prevent TNF-alpha induced adhesion of peripheral blood
      mononuclear cells (PBMCs) at human umbilical vein endothelial cells (HUVECs).
      Additionally, therapeutical monoclonal anti-TNF-alpha antibodies were proofed for
      inhibitory effects of TNF-alpha mediated activation of HUVECs. RESULTS: We have
      shown, in vitro, that beads coated with polyclonal or monoclonal anti-TNF-alpha
      antibodies were able to significantly reduce monocyte adhesion. It was possible
      to decrease monocyte adhesion from nearly 9% to 3% within 2 hours and from 18% to
      2% within 6 hours of TNF-alpha treatment by the simultaneous use of beads coated
      with polyclonal anti-TNF-alpha antibodies. Beads coated with monoclonal anti-TNF
      alpha antibodies could even prevent monocyte adhesion within the first 2 hours,
      and reduced monocyte adhesion to 2% during 6 hours of incubation with TNF-alpha.
      On the other hand, application of therapeutic anti-TNF-alpha antibodies showed no
      significant difference compared to the measured monocyte adhesion values of
      activated endothelial cells. CONCLUSION: Adsorption techniques using specific
      adsorbents, possibly used in MDS (Microspheres-Based Detoxification System), are
      efficient in specific reduction of TNF-alpha and pathophysiological consequences,
      since monocyte adhesion at activated HUVECs was shown to be reduced.

PMID- 17219355
TI  - Promotion of angiogenesis in tissue engineering: developing multicellular
      matrices with multiple capacities.
AB  - One of the aims of tissue engineering is to be able to develop multi-tissue
      organs in the future. This requires the optimization of conditions for the
      differentiation of multiple cell types and maintenance of the differentiated
      phenotype within complex engineered tissues. The goal of this study was to
      develop prototype tissue engineered matrices to support the simultaneous growth
      of different cell types with a particular focus on the angiogenic process. We
      examined two different matrix compositions for the promotion of blood vessel and
      tube formation. A fibrin-based matrix with the addition of a combination of
      growth factors supported vascular growth and the invasion of inflammatory cells.
      Using this fibrin matrix, in combination with a collagen-based hydrogel, a simple
      in vitro model of the cornea with adjacent sclera was developed that was complete
      with innervation and vascular structures. In addition, we showed that collagen
      based matrices were effective in delivering mononuclear endothelial progenitor
      cells to ischemic tissue in vivo, and allowing these cells to incorporate into
      vascular structures. It is anticipated that with further development, these
      matrices have potential for use as delivery matrices for cell transplantation and
      for in vitro study purposes of multiple cell types.

PMID- 17219356
TI  - Autonomously contracting human cardiomyocytes generated from adult pancreatic
      stem cells and enhanced in co-cultures with myocardial biopsies.
AB  - Myocardial regeneration with artificially applied cardiomyocytes is emerging as a
      promising issue of significant scientific and clinical impact. Nevertheless the
      source of cells for human cardiomyocyte differentiation especially from adult
      tissue is still unclear. We hypothesized that human pancreatic stem cells may
      differentiate into cardiomyocyte-like cells and may increase in number when co
      cultured with myocardial tissue. Adult stem cells were harvested from pancreatic
      tissue of patients undergoing operative procedures including the pancreas. The
      cells were selected, cultured and passaged. To promote self-differentiation into
      cardiomyocytes, human pancreatic stem cells were co-cultered with biopsies of
      human myocardium. After co-culture and breeding, cells were phenotyped as well
      with respect to RNA, protein and cardiomyocyte specificity at the electron
      microscopic level.Pancreatic stem cells have already differentiated spontaneously
      into cardiomyocyte-like cells performing netlike cell clusters with rare but
      distinct multilocular cellular autonomous contractions with a frequency of about
      20 beats per minute. The number of contracting areas however could be enhanced by
      co-culture with human myocardial biopsies. On RNA and protein levels as well as
      in electron-microscopy, evidence for cardiomyocyte specificity is shown. To the
      best of our knowledge this is the first report demonstrating the feasibility of
      generating autonomously contracting cardiomyocyte-like cells from adult human
      pancreatic stem cells and their enhancement by myocardial co-culture. This
      procedure might prove to be an alternative source and method for myocardial
      regenerative medicine.

PMID- 17219357
TI  - Enhanced dermal regeneration using modified collagen scaffolds: experimental
      porcine study.
AB  - Ongoing research has achieved much progress towards the development of new
      artificial skin substitute products. However, effective implant material for
      correcting full-thickness defects (such as those arising from extensive burns,
      tumor resection, hereditary or congenital defects and chronic wounds) has not yet
      become available. Following split-thickness skin grafting, contraction and scar
      formation are unavoidable. These phenomena are believed to be due to poor dermis
      regeneration. Collagen dermis substitute has been developed for the treatment of
      deep, poorly vascularized tissue defects. However, their application is
      problematic, because scaffolds of this kind fail to adequately induce the
      neoangiogenesis needed for regeneration. To overcome these shortcomings a number
      of matrices have been chemically modified. Furthermore, these matrices first
      require implantation and follow-up by skin grafting 3 to 5 weeks later. In this
      article we describe new materials made of modified collagen which enhance dermal
      regeneration and neoangiogenesis. The procedure was applied in successfully
      dealing with full-thickness defects in pigs, with subsequent split-thickness skin
      grafting being performed immediately afterwards. Histological findings revealed
      that the neodermis obtained resembles a normal dermis structure. These scaffolds
      have the potential of serving as an off-the-shelf skin replacement in the
      reconstruction of deep wounds, thus supporting wound-healing processes.

PMID- 17219358
TI  - Tribological characterization of surface-treated commercially pure titanium for
      femoral heads in total hip replacement: a feasibility study.
AB  - Most noncemented total hip replacements combine a titanium alloy stem, a CoCrMo
      femoral head and an ultra-high molecular weight polyethylene (UHMWPE) acetabular
      cup. In spite of its nickel content of up to 1% and the resulting
      biocompatibility issues in some clinical situations, the higher cost and some
      difficulties in machining, CoCrMo alloy is preferred to titanium alloys thanks to
      its outstanding tribological properties, higher hardness and elastic modulus.
      Nowadays most of the heads of hip prostheses use CoCrMo as bearing material. The
      present study investigates the effect of various surface treatments and
      combinations of treatments, such as electrochemical oxidation (anodization),
      laser surface melting and barrel polishing, on the tribological properties of
      commercially pure grade 2 titanium. The aim of the study was to characterize
      surface treatments capable of improving the tribological properties of titanium
      surface to the same extent as CoCrMo. The tribological properties were
      characterized by multidirectional pin-on-flat screening wear tests, using UHMWPE
      pins as bearing surface. The experiments showed the possibility of improving the
      wear resistance of titanium to the degree of CoCrMo. Although further efforts
      will be required to optimize the treatments studied, the results are encouraging
      enough to warrant pursuing this direction of investigation.

PMID- 17219359
TI  - Hemolysis evaluation of centrifugal pumps using microcapsule suspension.
AB  - OBJECTIVES: Bovine and human blood has been widely used for in vitro hemolysis
      testing to evaluate centrifugal cardiac assist pumps. However, results from such
      tests are complicated by variations in the susceptibility of individual red blood
      cells to shear. The objective of this study was to evaluate the use of
      microcapsule suspension as an alternative to bovine or human blood for hemolysis
      testing. METHODS: Microcapsule suspensions of 100 micro m maximal diameter
      (average 79.1 micro m) with a polyurethane membrane were used. Each microcapsule
      contained a leuco dye, which was used to measure "hemolysis" in the suspension
      after exposure to mechanical stress. Six centrifugal pumps were used to measure
      and compare the hemolysis values of microcapsule suspensions, bovine blood and
      human blood. RESULTS: Correlations were significant between the hemolysis values
      measured using microcapsule suspensions and those using bovine blood (R = 0.965,
      p = 0.002) and human blood (R = 0.940, p = 0.005). CONCLUSIONS: Microcapsule
      suspension can be successfully used instead of blood to compare the relative
      hemolytic performance of centrifugal blood pumps.

PMID- 17219360
TI  - The "French Hemodiafe Trial": this study is neither decisive nor definitive in
      resolving the controversy on renal replacement therapy in ICU.
AB  - This short review paper addresses a recently published study on the controversy
      concerning the type of renal replacement therapy (RRT) used in ICU. It proposes a
      somewhat different point of view regarding this study, based on the numerous
      problems that have been identified with it. Indeed, given these shortcomings, the
      study conclusions are somewhat misleading and are not effectively supported by
      the trial data. If the treatment doses were comparable and kept constant in the
      OIHDO group, then the results may well have been strikingly different. In keeping
      with all drugs used in medicine, dose is crucial and should have remained
      unchanged by the investigators during the study in order to be able to draw valid
      conclusions based on the evidence. There is a need for a further study comparing
      CRRT and IHD. This should be better designed in terms of the exclusion criteria,
      delivered dose of CVVH (35 ml/kg/h) and IHD, timing of treatment and should also
      examine more secondary endpoints. This may answer many of the outstanding issues
      and provide a balanced opinion about this study and its real importance in ICU
      practice. Finally, this study does not have the scientific power (as explained by
      the accompanying editorial by Kellum) to put an end to the ICU controversy
      regarding the choice of RRT in acute renal failure while in ICU. Therefore, there
      is an urgent need for a better designed study regarding this controversy.

PMID- 17219361
TI  - An improved algorithm for analytical gradient evaluation in resolution-of-the
      identity second-order Moller-Plesset perturbation theory: application to alanine
      tetrapeptide conformational analysis.
AB  - We present a new algorithm for analytical gradient evaluation in resolution-of
      the-identity second-order Moller-Plesset perturbation theory (RI-MP2) and
      thoroughly assess its computational performance and chemical accuracy. This
      algorithm addresses the potential I/O bottlenecks associated with disk-based
      storage and access of the RI-MP2 t-amplitudes by utilizing a semi-direct batching
      approach and yields computational speed-ups of approximately 2-3 over the best
      conventional MP2 analytical gradient algorithms. In addition, we attempt to
      provide a straightforward guide to performing reliable and cost-efficient
      geometry optimizations at the RI-MP2 level of theory. By computing relative
      atomization energies for the G3/99 set and optimizing a test set of 136
      equilibrium molecular structures, we demonstrate that satisfactory relative
      accuracy and significant computational savings can be obtained using Pople-style
      atomic orbital basis sets with the existing auxiliary basis expansions for RI-MP2
      computations. We also show that RI-MP2 geometry optimizations reproduce molecular
      equilibrium structures with no significant deviations (>0.1 pm) from the
      predictions of conventional MP2 theory. As a chemical application, we computed
      the extended-globular conformational energy gap in alanine tetrapeptide at the
      extrapolated RI-MP2/cc-pV(TQ)Z level as 2.884, 4.414, and 4.994 kcal/mol for
      structures optimized using the HF, DFT (B3LYP), and RI-MP2 methodologies and the
      cc-pVTZ basis set, respectively. These marked energetic discrepancies originate
      from differential intramolecular hydrogen bonding present in the globular
      conformation optimized at these levels of theory and clearly demonstrate the
      importance of long-range correlation effects in polypeptide conformational
      analysis.

PMID- 17219364
TI  - Activation of dendritic cells by the Gal-lectin of Entamoeba histolytica drives
      Th1 responses in vitro and in vivo.
AB  - Amebiasis is a human disease caused by the protozoan intestinal parasite
      Entamoeba histolytica. Vaccine development has focused on the parasite's surface
      galactose-N-acetyl-D-galactosamine inhibitable lectin (Gal-lectin) as a
      protective antigen. The Gal-lectin is immunogenic and has been shown to induce
      Th1 cytokines in vitro and in vivo. The immunological basis of the protective
      immune response elicited by the Gal-lectin is unknown. In this study, we
      investigated the response of BALB/c bone marrow-derived DC to E. histolytica Gal
      lectin. Incubation of immature DC with Gal-lectin resulted in activation and
      maturation after 24 h. FACS analysis demonstrated an up-regulation of DC
      maturation markers CD80, CD86, CD40 and MHC class II upon exposure to Gal-lectin.
      The Gal-lectin also induced DC production of IL-12, indicating a Th1 response.
      Gal-lectin-activated DC were able to stimulate T cell proliferation in an
      allogeneic mixed leukocyte reaction and adoptive transfer of Gal-lectin-treated
      DC into naive mice resulted in IFN-gamma-producing Gal-lectin-sensitized T cells.
      The activation of DC by Gal-lectin was mediated by MAPK and NF-kappaB. These
      findings indicate that E. histolytica Gal-lectin is a potent vaccine antigen
      capable of directly initiating DC maturation and activation characterized by Th1
      cytokine production.

PMID- 17219365
TI  - IL-18, but not IL-12, is required for optimal cytokine production by influenza
      virus-specific CD8+ T cells.
AB  - The potent innate cytokines IL-12 and IL-18 are considered to be important
      antigen-independent mediators of IFN-gamma production by NK cells and T
      lymphocytes. The present analysis addresses the physiological role of IL-12 and
      IL-18 in the generation of virus-specific CD8+ T cells. Both wt C57BL/6J (B6)
      mice and mice with disrupted IL-12p40 (IL-12p40(-/-)) or IL-18 (IL-18(-/-)) genes
      were infected with an influenza A virus and the characteristics of the resultant
      epitope-specific CD8+ T cell responses were compared. While IL-12 appeared to
      have no notable effect on either virus growth or on CD8+ T cell response
      profiles, the absence of IL-18 was associated with delayed virus clearance from
      the lung and, despite normal numbers, a significantly reduced production of IFN
      gamma, TNF-alpha, and IL-2 by epitope-specific CD8+ T cells. While this cytokine
      phenotype was broadly maintained in IL-12p40/IL-18 double-knockout mice, no
      evidence was seen for any additive effect. Together, our results suggest that IL
      18, but not IL-12, induces optimal, antigen-specific production of key cytokines
      by CD8+ T cells for the efficient clearance of influenza virus from the lungs of
      infected mice.

PMID- 17219366
TI  - Erosion of interaction networks in reduced and degraded genomes.
AB  - Unlike eukaryotes, which often recruit duplicated genes into existing protein
      protein interaction (PPI) networks, the low levels of gene duplication coupled
      with the high probability of lateral transfer of novel genes alters the manner in
      which PPI networks can evolve in bacteria. By inferring the PPIs present in the
      ancestor to contemporary Gammaproteobacteria, we were able to trace the changes
      in gene repertoires, and their consequences on PPI network evolution, in several
      bacterial lineages that have independently undergone reductions in genome size
      and genome contents. As genomes degrade, virtually all multi-partner proteins
      have lost interactors; however, the overall average number of connections
      increases due to the preferential elimination of proteins that interact with only
      one other protein partner. We also studied the effect of lateral gene transfer on
      PPI network evolution by analyzing the connectivity of genes that have been
      gained along the Escherichia coli lineage, as well as those acquired genes
      subsequently silenced in Shigella flexneri, since diverging from the
      gammaproteobacterial ancestor. The situation in PPI networks, in which newly
      acquired genes preferentially attach to the hubs of the network, contrasts that
      observed in metabolic networks, which evolve by the peripheral gain and loss of
      genes, and in regulatory networks, in which high connectivity increases the
      propensity of loss.

PMID- 17219367
TI  - Phylogeographic inferences from the mtDNA variation of the three-toed skink,
      Chalcides chalcides (Reptilia: Scincidae).
AB  - Genetic diversity was analyzed in Chalcides chalcides populations from peninsular
      Italy, Sardinia, Sicily and Tunisia by sequencing 400 bp at the 5' end of the
      mitochondrial gene encoding cytochrome b (cyt b) and by restriction fragment
      length polymorphism (RFLP) analysis of two mitochondrial DNA segments (ND-1/2 and
      ND-3/4). The results of the phylogenetic analysis highlighted the presence of
      three main clades corresponding with three of the four main geographical areas
      (Tunisia, Sicily and the Italian peninsula), while Sardinia proved to be closely
      related to Tunisian haplotypes suggesting a colonization of this island from
      North Africa by human agency in historical times. On the contrary, the splitting
      times estimated on the basis of cyt b sequence data seem to indicate a more
      ancient colonization of Sicily and the Italian Peninsula, as a consequence of
      tectonic and climatic events that affected the Mediterranean Basin during the
      Pleistocene. Finally, the analysis of the genetic variability of C. chalcides
      populations showed a remarkable genetic homogeneity in Italian populations when
      compared to the Tunisian ones. This condition could be explained by a rapid post
      glacial expansion from refugial populations that implied serial bottlenecking
      with progressive loss of haplotypes, resulting in a low genetic diversity in the
      populations inhabiting the more recently colonized areas.

PMID- 17219368
TI  - First-trimester uterine artery Doppler and spontaneous preterm delivery.
AB  - OBJECTIVES: To assess the relationship between first-trimester uterine artery
      Doppler measurements and spontaneous preterm delivery. METHODS: This was a
      retrospective analysis of uterine artery Doppler findings at 11-14 weeks in 73
      singleton pregnancies with spontaneous preterm labor and 2417 pregnancies
      delivered at term. RESULTS: The uterine artery mean resistance index (RI) was
      0.68 (coefficient of variation 19%) and 0.69 (17%) in the preterm and term
      delivery groups, respectively (P = 0.35). The mean pulsatility index (PI) was
      1.42 (39%) and 1.42 (46%) in the term and preterm delivery groups, respectively
      (P = 0.95). Bilateral diastolic notches were present in 34% of preterm deliveries
      and 33% of controls (P = 0.84). Restricting the analysis to the 19 pregnancies
      with preterm delivery before 34 weeks of gestation, no significant difference
      from controls was observed for RI (mean 0.71, coefficient of variation 11%, P =
      0.41), PI (mean 1.56, coefficient of variation 29%, P = 0.27) or the number of
      bilateral notches (42%, P = 0.41). CONCLUSIONS: Despite pathological evidence
      suggesting that defective placentation is associated with spontaneous preterm
      delivery, first trimester uterine artery resistance, as assessed by Doppler
      ultrasound investigation, is not different in pregnancies subsequently
      complicated by preterm labor compared to pregnancies delivered at term. This
      finding may be explained by a late failure of trophoblast development in cases
      destined to deliver preterm.

PMID- 17219369
TI  - Insights from diploblasts; the evolution of mesoderm and muscle.
AB  - The origin of both mesoderm and muscle are central questions in metazoan
      evolution. The majority of metazoan phyla are triploblasts, possessing three
      discrete germ layers. Attention has therefore been focused on two outgroups to
      triploblasts, Cnidaria and Ctenophora. Modern texts describe these taxa as
      diploblasts, lacking a mesodermal germ layer. However, some members of Medusozoa,
      one of two subphyla within Cnidaria, possess tissue independent of either the
      ectoderm or endoderm referred to as the entocodon. Furthermore, members of both
      Cnidaria and Ctenophora have been described as possessing striated muscle, a
      mesodermal derivative. While it is widely accepted that the ancestor of Eumetazoa
      was diploblastic, homology of the entocodon and mesoderm as well as striated
      muscle within Eumetazoa has been suggested. This implies a potential
      triploblastic ancestor of Eumetazoa possessing striated muscle. In the following
      review, I examine the evidence for homology of both muscle and mesoderm. Current
      data support a diploblastic ancestor of cnidarians, ctenophores, and triploblasts
      lacking striated muscle.

PMID- 17219370
TI  - Explaining the freemartin: Tandler and Keller vs. Lillie and the question of
      priority.
AB  - The correct explanation for the freemartin phenotype in the female twin of a
      female-male pair in cattle was first reported by Tandler and Keller (1911.
      Deutsche Tierarzt Wochenschr 19:148-149). This same explanation for the
      freemartin was independently discovered by Lillie (1916. Science 43:611-613).
      Today both set of scientists are given credit for this discovery; it is the basis
      for much of the subsequent work on the developmental basis for sex
      differentiation in vertebrates. Even though Lillie published after Keller and
      Tandler, he gets credit for this discovery because: (1) Keller and Tandler
      published in a veterinary journal and as a consequence their work was not
      disseminated as broadly throughout the larger scientific community; this problem
      was compounded by the fact that their definitive 1916 paper was published under
      wartime conditions during World War I, and (2) Lillie was an influential
      scientist with a group of graduate students who could elaborate on and extend his
      work; they published a number of papers on the freemartin. At some point while
      Lillie was doing his initial work on the freemartin he may have become aware that
      Keller and Tandler were also working on the freemartin problem; this information
      may have shaped his decision on when to publish.

PMID- 17219371
TI  - Postpartum evaluation of the anal sphincter by transperineal three-dimensional
      ultrasound in primiparous women after vaginal delivery and following surgical
      repair of third-degree tears by the overlapping technique.
AB  - OBJECTIVE: Intrapartum damage to the anal sphincter is an important factor in
      fecal incontinence. Recognized lacerations occur in 0.36-8.4% of vaginal
      deliveries, and occult sphincter damage in up to 35% of primiparous women. We
      examined the role of three-dimensional transperineal ultrasound (3DTUS) in the
      evaluation of the anal sphincter in primiparous women after vaginal delivery and
      after surgical repair of third-degree intrapartum tears by the overlapping
      technique. METHODS: During 2004-2005 139 primiparous women without clinically
      recognized third- to fourth-degree anal sphincter tears were prospectively
      studied 24-72 h postpartum (Group 1) and 13 primiparous women were examined 48 h
      to 4 months following surgical repair of third-degree tears with the overlapping
      technique (Group 2). A 3D 5-9-MHz transvaginal probe was placed in the area of
      the fourchette and perineal body in transverse and sagittal planes and 2-4
      volumes were stored. The parameters studied were: examination duration;
      continuity of the internal and external sphincters; occult sphincter damage;
      internal sphincter and external sphincter width-measured 1.5 cm from the distal
      margin of the anus-at the '12, 3, 6 and 9 o'clock positions'; length of the
      posterior internal sphincter. RESULTS: Scanning was possible in all women and the
      stored volumes were adequate in 127/139 (91.4%) cases. Mean examination time was
      3.5 min. In Group 1, occult sphincter defect was suspected in 10/127 women
      (7.9%). These patients were excluded from measurement calculations, leaving 117
      cases for analysis. The internal sphincter was consistently visualized in all the
      remaining patients (n = 117), while the external sphincter was fully visualized
      in 99/117 women (84.6%), and partially visualized in the remainder. Mean internal
      sphincter thickness was 2.60, 2.55, 2.60 and 2.72 mm at the 12, 3, 6 and 9
      o'clock positions, respectively, and mean internal sphincter length was 3.34 cm.
      Mean external sphincter thickness was 4.15, 4.20, 4.21 and 4.20 mm at the 12, 3,
      6 and 9 o'clock measurement points. In Group 2, 3DTUS confirmed anatomic
      abnormalities in all the women in the area surrounding the 12 o'clock position.
      Evaluation of sphincter tears and their position and length was possible using
      the longitudinal view. Thinning of the internal sphincter in the area of damage
      and thickening on the opposite side, the 'half moon sign', sphincter
      discontinuity, thickening of the external sphincter in the area of repair and
      abnormality of mucous folds, seemed to be common signs of third-degree
      intrapartum sphincter tears, even after repair. CONCLUSIONS: 3DTUS is an
      accessible and promising method for postpartum sphincter evaluation, that is
      apparently well tolerated by patients. Reference data for sphincter anatomy
      representative of findings at transperineal ultrasound in primiparous women in
      the postpartum period have been established.

PMID- 17219372
TI  - Maternal control of pattern formation in Xenopus laevis.
AB  - We review the essential role of maternal factors in pattern formation for Xenopus
      laevis, focusing on VegT, Vg1, and Wnt11. Results from loss of function
      experiments demonstrate a clear requirement for these genes in germ layer
      specification, dorsal-ventral axis formation, and convergence extension. We also
      discuss these genes in the broader context of metazoan development, exploring
      whether and how their functions in the X. laevis model organism may or may not be
      conserved in other species. Wnt11 signaling in particular provides a classic
      example where understanding context in development is crucial to understanding
      function. Genomic sequencing, gene expression, and functional screening data that
      are becoming available in more species are providing invaluable aid to decoding
      and modeling signaling pathways. More work is needed to develop a comprehensive
      catalog of the Wnt signaling, T-box, and TGF-beta genes in metazoans both near
      and far in evolutionary distance. We finally discuss some specific experimental
      and modeling efforts that will be needed to understand the behavior of these
      signaling networks in vivo so that we can interpret these critical pathways in an
      evolutionary framework.

PMID- 17219373
TI  - Late stent thrombosis: considerations and practical advice for the use of drug
      eluting stents: a report from the Society for Cardiovascular Angiography and
      Interventions Drug-eluting Stent Task Force.

PMID- 17219374
TI  - A haplotype-linkage analysis method for estimating recombination rates using
      dense SNP trio data.
AB  - Meiotic recombination is an important evolution force in shaping human genomes
      and creating human diversity. Recent explorations suggest that meiotic
      recombination events tend to happen in certain regions of the genome, leading to
      the hypothesis of recombination hot spots. To identify such hot spots, we
      describe an empirical method for estimating the recombination rate, which
      reflects both historical and current meiotic events, using unphased genotypes
      from nuclear families, in particular, parents-child trios. The key idea is that
      use of the haplotypic polymorphisms with multiple adjacent SNPs will increase the
      number of informative meioses and hence would improve the power of linkage
      analysis. Since haplotypes of individuals are not directly observed, e.g., in
      HapMap data, we infer the haplotypes simultaneously while estimating
      recombination rate. We refer this described method as haplotype-linkage (HALIN)
      method. Our simulation results show that HALIN gives unbiased estimates of
      recombination rate. We apply HALIN to analyze the genotype data of chromosome 20
      from HapMap data and compare the results to the results using two existing
      methods, Bayesian coalescent method described by McVean et al. [2004] science
      304:581-584 and empirical method by Clarke and Cardon ([2005] Genetics). Results
      suggest that HALIN identified 75 hot spots on chromosome 20, and 85% of them are
      also identified by the method by McVean et al. ([2004] science 304:581-584), in
      addition to a few new hot spots. In comparison with Clarke and Cardon's result,
      estimated recombination rates (RRs) under these 75 hot spots are significantly
      greater than those outside of hot spots, which support the general consistency in
      discovering recombination hot spots between two methods.

PMID- 17219375
TI  - Type I error rates in association versus joint linkage/association tests in
      related individuals.
AB  - Positional gene discovery on pedigree data typically involves initial gross
      localization by linkage analysis with subsequent finer localization by
      association analysis in areas that show evidence of linkage. We examine the
      effect of including linkage information when testing for association in the
      context of variance-components-based pedigree analysis. We present simulation
      experiments showing that, at least in the extreme case of a rare private allele,
      failing to include the linkage variance component in the association model
      results in excessive Type I error that increases with allele copy number and/or
      quantitative trait locus (QTL) effect size. Joint estimation of the linkage
      variance component in the association model reduces Type I error to nominal
      expectations. This holds whether allele-sharing probabilities are estimated from
      a polymorphic marker or from the very single-nucleotide polymorphism (SNP) being
      tested for association, although the latter provides much less power. These
      results support the idea that an appropriate association analysis must test both
      the random effect of shared marker alleles (linkage) and the mean effects of the
      marker genotypes (association).

PMID- 17219376
TI  - Analysis on binary responses with ordered covariates and missing data.
AB  - We consider the situation of two ordered categorical variables and a binary
      outcome variable, where one or both of the categorical variables may have missing
      values. The goal is to estimate the probability of response of the outcome
      variable for each cell of the contingency table of categorical variables while
      incorporating the fact that the categorical variables are ordered. The
      probability of response is assumed to change monotonically as each of the
      categorical variables changes level. A probability model is used in which the
      response is binomial with parameters p(ij) for each cell (i, j) and the number of
      observations in each cell is multinomial. Estimation approaches that incorporate
      Gibbs sampling with order restrictions on p(ij) induced via a prior distribution,
      two-dimensional isotonic regression and multiple imputation to handle missing
      values are considered. The methods are compared in a simulation study. Using a
      fully Bayesian approach with a strong prior distribution to induce ordering can
      lead to large gains in efficiency, but can also induce bias. Utilizing isotonic
      regression can lead to modest gains in efficiency, while minimizing bias and
      guaranteeing that the order constraints are satisfied. A hybrid of isotonic
      regression and Gibbs sampling appears to work well across a variety of scenarios.
      The methods are applied to a pancreatic cancer case-control study with two
      biomarkers.

PMID- 17219377
TI  - Prenatal diagnosis of malformations of cortical development by dedicated
      neurosonography.
AB  - OBJECTIVE: Malformations of cortical development (MCD) are rarely diagnosed in
      utero. We describe and compare the ultrasonographic and pathology findings in a
      cohort of fetuses with MCD. METHODS: Fetuses with MCD were identified among all
      fetuses evaluated for suspected brain anomalies at the Fetal Neurology Clinic,
      and the ultrasonographic findings were compared with the results of the pathology
      examination. RESULTS: We suspected the presence of MCD by ultrasonography in 23
      fetuses. The mean gestational age at the time of ultrasound diagnosis was 26.2
      (range, 18-40) weeks. The ultrasonographic findings leading to the diagnosis of
      MCD were abnormally overdeveloped gyri and sulci for gestational age (n = 7),
      delay in sulcation (n = 5), abnormally thin cortex (n = 5) abnormally wide and
      broad sulci (n = 3), bulging into the lateral ventricle (n = 1), cortical cleft
      (n = 1), and multiple intraparenchymal echogenic nodules (n = 1). All fetuses had
      associated central nervous system (CNS) and/or non-CNS anomalies. Pathology
      examination (performed in 17 fetuses) confirmed MCD in 16. CONCLUSIONS: Cortical
      malformations can be diagnosed in utero by ultrasonography based on the presence
      of specific deviations from the normal pattern of development. The identified
      cases may represent the more severe forms in the MCD spectrum. The pathology
      findings do not always conform to the current classification systems of MCD but
      help in differentiating between possible genetic and acquired etiologies and in
      some cases provide a definitive syndromic diagnosis.

PMID- 17219378
TI  - Rapid, non-destructive, cell-based screening assays for agents that modulate
      growth, death, and androgen receptor activation in prostate cancer cells.
AB  - BACKGROUND: We developed non-invasive, cell-based screening assays to rapidly and
      biologically assess factors that modulate prostate cancer growth and affect
      androgen receptor (AR) activity. METHODS: LNCaP cells, which stably express
      enhanced green fluorescent protein (EGFP) either constitutively or upon AR
      activation, were treated with a variety of agents, and then monitored by
      fluorescence and MTS assays for dose-dependent changes in cell number and AR
      activity. RESULTS: The assays were validated for rapid, fluorescence-based,
      quantitative measurement for the presence of growth and AR modulators. Using
      these assays, we found that osteoblast conditioned media (CM) enhanced prostate
      cancer cell growth, but not AR activity. After priming with androgen (<1 nM
      R1881), forskolin or the pesticide dichlorvos enhanced AR activation, whereas
      interleukin-6 (IL-6) inhibited it. CONCLUSION: These non-destructive, cell-based
      assays enable rapid systematic monitoring of the effects of drugs or complex
      mixtures on prostate cancer cell growth and/or AR activity.

PMID- 17219379
TI  - Ten-year survival and cardiovascular mortality in patients with advanced prostate
      cancer primarily treated by intramuscular polyestradiol phosphate or orchiectomy.
AB  - BACKGROUND: The aim of the study was to evaluate overall and prostate cancer
      (PCa) specific survival with special attention to cardiovascular (CV) mortality
      in patients primarily treated by parenteral polyestradiol phosphate (PEP) 240
      mg/month or with orchiectomy (OE), taking into account the effect of pretreatment
      diseases and medication, and later PCa therapies. METHODS: The present
      Finnprostate 6 study (10-year follow-up) consisted of 244 patients with locally
      advanced PCa (T3-4 M0) and 200 patients with metastatic PCa (T1-4 M1). Patients
      were randomized to OE or PEP therapy. The T3-4 M0 and T1-4 M1 patients were
      analyzed separately. RESULTS: There was no difference in overall or PCa specific
      survival between the primary therapy groups in T3-4 M0 or T1-4 M1 patients. In
      the T3-4 M0 patients the primary treatment (PEP vs. OE) was statistically
      significantly associated with a risk of CV deaths (P = 0.001). Such an
      association was not found in the T1-4 M1 patients. CONCLUSIONS: The primary PEP
      and OE therapies are equal in terms of overall and PCa specific survival in
      patients with T3-4 M0 or T1-4 M1 disease. In T3-4 M0 patients PEP increases the
      risk of CV deaths compared to OE but not in T1-4 M1 patients.

PMID- 17219381
TI  - Gain of chromosome X in prostatic atrophy detected by CGH and FISH analyses.
AB  - BACKGROUND: Focal atrophy is presumed to be an indirect forerunner of prostate
      cancer. The aim of this study was to examine genetic alterations in prostate
      epithelia deriving from atrophic areas and compare these findings with those of
      cells deriving from paired prostate cancer in the same patient. METHODS: Formalin
      fixed paraffin wax-embedded prostatectomy specimens from 20 prostate cancer
      patients were utilized in this study. Comparative Genomic Hybridization (CGH) was
      performed on atrophic areas. To validate the CGH results, Fluorescence in Situ
      Hybridization (FISH) analysis was performed on atrophic areas and paired cancer
      tissue. RESULTS: Gain of the whole chromosome X was found as sole aberration in
      seven (70%) atrophic tissues by CGH. A gain of centromere X was observed in 13
      (68.4%) atrophic areas and in 18 (90%) cancer tissues using FISH. CONCLUSIONS:
      Our investigation reconfirms the genetical instability of cells of the atrophic
      acini and attention of relevance of gain of chromosome X in atrophic areas.

PMID- 17219380
TI  - Prothrombotic effect of prostasomes of metastatic cell and seminal origin.
AB  - BACKGROUND: Prostasomes are secretory granules produced by the glandular
      epithelial cells of the prostate. Seminal prostasomes contain high amounts of
      Tissue Factor (TF) but no studies of TF on malignant cell prostasomes have been
      made. Here we compare the expression, phosphorylation, and function of TF on
      prostasomes of different origin. METHODS: TF was detected on prostasomes isolated
      from seminal fluid and human prostate cancer cell lines (PC-3, DU145, and LNCaP)
      using FACS and enzyme immunoassay (EIA). Incubation of prostasomes with
      radioactive ATP under conditions favoring protein kinase A activity led to
      phosphorylation of TF as detected by immunoprecipitation and SDS-PAGE. The
      prothrombotic effect of prostasomes was investigated in whole blood and
      recalcified plasma. Blocking experiments were performed using anti-TF antibodies
      and corn trypsin inhibitor. RESULTS: TF was expressed on all tested prostasome
      preparations with lowest values found for seminal ones. Prostasomal TF was the
      main endogenous substrate for prostasomal protein kinase A. All tested prostasome
      preparations greatly enhanced the rate of clot formation in a dose-dependent
      fashion, that is, the clotting capability of prostasomes seemed to be related to
      the extent of their expression of TF. In addition, the density of the clot varied
      between different prostasome preparations. When incubated in whole blood,
      prostasomes were found to associate to WBC thereby inducing them to express and
      release TF. CONCLUSIONS: These data show that TF is overexpressed and also
      subjected to phosphorylation by malignant cell prostasomes. This suggests major
      roles for prostasomes in thrombotic events that occur in some advanced cases of
      prostate cancer.

PMID- 17219382
TI  - Characterization of human prostate and breast cancer cell lines for experimental
      T cell-based immunotherapy.
AB  - BACKGROUND: In order to develop experimental immunotherapy for prostate and
      breast cancer it is of outmost importance to have representative target cell
      lines that through human leukocyte antigen (HLA) class I molecules present
      relevant levels of peptides from tumor-associated antigens for cytotoxic T
      lymphocyte (CTL) recognition. METHODS: We sequenced the HLA-A and HLA-B loci of
      eight commonly used prostate and breast cancer cell lines and analyzed the
      surface expression of HLA-ABC, HLA-DR, CD40, CD80, CD86, and CD54 by flow
      cytometry. We also analyzed the cell lines for mRNA expression from 25 genes
      reported to be specifically or preferentially expressed by prostate cells.
      RESULTS: Among the analyzed cell lines we found that LNCaP, PC-346C and MCF-7 are
      HLA-A*0201 positive. However, the HLA-A2 expression level is low and only MCF-7
      upregulates HLA-A2 in response to IFN-gamma stimulation. MCF-7 also expresses
      high levels of CD54, which further improve its value as a CTL target cell line.
      On the other hand, LNCaP and PC-346C express 25 and 23 out of 25 prostate-related
      genes, respectively, while MCF-7 expresses 16 out of 25 genes. CONCLUSIONS: None
      of the analyzed prostate cancer cell lines are optimal CTL target cells. However,
      MCF-7 could in many cases be used as a complement to HLA-A*0201 positive prostate
      cancer cells. The LNCaP and PC-346C cell lines are rich sources of prostate
      related antigens that may be valuable for cancer vaccine development.

PMID- 17219383
TI  - Favorable indications for hepatectomy in patients with liver metastasis from
      gastric cancer.
AB  - BACKGROUND: The prognosis of patients with liver metastasis from gastric cancer
      (LMGC) is dismal. The purpose of this study was to review our recent outcomes of
      hepatectomy for LMGC and to determine the suitable candidates for surgery. STUDY
      DESIGN: The outcomes of 37 patients with LMGC who underwent hepatectomy between
      1990 and 2005 were assessed. No extrahepatic distant metastasis and feasibility
      of macroscopic curative resection were requisite indications for surgery. The
      prognostic values of clinicopathological factors were assessed by univariate and
      multivariate analyses. RESULTS: There was no in-hospital mortality. The median
      survival time and overall 5-year survival rate after hepatectomy of the patients
      with LMGC were 31 months and 11%, respectively. Intrahepatic recurrence following
      hepatectomy was found in 23 patients (62%). Variables independently associated
      with poor survival were bilobar metastasis (P = 0.002, CI = 1.9-16.3) and a
      maximum tumor diameter of >or= 4 cm (P = 0.006, CI = 1.4-7.7). The depth of the
      primary tumor and the timing of metastasis were not associated with survival.
      CONCLUSIONS: Surgical resection for LMGC may be indicated in patients with
      unilobar metastasis and/or tumors less than 4 cm in diameter. Synchronous
      metastasis is not a contraindication for hepatectomy.

PMID- 17219384
TI  - "No one else sees the difference: "family members' perceptions of changes in
      persons with preclinical Huntington disease.
AB  - Manifestations of Huntington disease (HD) prior to clinical diagnosis are not
      well understood. This study documents adult family members' perceptions of
      changes and their attempts to manage these changes in persons who had received a
      positive predictive molecular HD test prior to clinical diagnosis. Data were
      obtained from 19 adult family members in six focus groups in the US and Canada
      and one individual interview in the US. Changes reported by family members
      included problems in cognition and behavior, which are consistent with prior
      reports. In addition, family members observed changes in motor functioning, the
      ability to complete usual activities at work or at home, and interpersonal
      relationships with family and friends. Family members attempted to manage these
      changes by taking on new responsibilities and preparing for future caregiving.
      Lack of information about preclinical HD, difficulty in understanding changes
      that may represent early stages of HD, and efforts to maintain secrecy of the
      preclinical HD situation contribute to compromising the abilities of family
      members to respond to changes in the person with preclinical HD. Findings provide
      insights into alterations in cognition, behavior, and functioning observed by the
      family members prior to clinical diagnosis. Findings further support the need for
      a more comprehensive assessment and management of early HD symptoms as well as
      support for family members.

PMID- 17219385
TI  - Germline MYH mutations in a clinic-based series of Canadian multiple colorectal
      adenoma patients.
AB  - OBJECTIVES: MYH is a member of the DNA base excision repair (BER) pathway and
      mutations of this gene predispose to the development of colorectal neoplasia in
      an autosomal recessive transmission pattern. Our objective was to determine the
      significance of MYH mutations in a series of Canadian patients with multiple
      adenomas. METHODS: We screened for germline MYH mutations (by dHPLCO) in 20
      clinic-based multiple adenoma patients who were adenomatous polyposis coli (APC)
      mutation-negative. Suspected mutations were confirmed by sequence analysis.
      RESULTS: Six of 20 (30%) patients carried pathogenic biallelic MYH mutations, 1
      Y165C homozygote and 5 compound heterozygotes of other sequence variants. We
      identified three novel variants, Q377X, 1314delA, and P281L, which are likely
      pathogenic. Twenty-nine relatives of the Y90X/1103delC compound heterozygous
      carrier were also screened for germline MYH mutations, and 1 homozygous and 14
      heterozygous carriers were identified. CONCLUSIONS: Among patients with multiple
      adenomas, biallelic MYH mutations account for approximately 30% of APC mutation
      negative cases and two thirds of these carry mutations other than the "common"
      Y165C and G382D variants. Clinical screening algorithms which focus only on the
      Y165C and G382D alleles are inadequate since additional pathogenic mutations may
      be identified by screening the entire gene.

PMID- 17219386
TI  - Informative phenotypes for genetic studies of psychiatric disorders.
AB  - Despite its initial promise, there has been both progress and some set backs in
      genetic studies of the major psychiatric disorders of childhood and adulthood.
      Finding true susceptibility genes may be delayed because the most genetically
      informative phenotypes are not being used on a regular basis in linkage analysis
      and association studies. It is highly likely that using alternative phenotypes
      instead of DSM diagnostic categories will lead more rapid success in the search
      for these susceptibility genes. The objective of this paper is to describe the
      different types of informative phenotypes that can be employed in psychiatric
      genetic studies, to clarify their uses, to identify several methodologic issues
      the design and conduct of linkage and association studies that use alternative
      phenotypes and finally to suggest possible solutions to those difficulties. This
      is a conceptual review with a focus on methodological issues that may arise in
      psychiatric genetics and examples are taken from the literature on autism,
      schizophrenia, bipolar disorder, and alcoholism.

PMID- 17219387
TI  - Different criteria for radioactive sentinel lymph nodes has different impact on
      sentinel node biopsy in breast cancer patients.

PMID- 17219388
TI  - Clinical significance of the RT-PCR positive sentinel node in melanoma.
AB  - BACKGROUND: The clinical relevance of RT-PCR positivity for melanoma markers in
      the sentinel node remains controversial. Our purpose was to determine whether
      patients with a histologically negative but RT-PCR positive node were at an
      increased risk for recurrence than their RT-PCR negative counterparts. METHODS:
      Thirty-nine adult patients underwent sentinel node biopsies for melanoma between
      1998 and 2000. Each sentinel node was bivalved. Half was serially sectioned and
      examined by routine hematoxylin and eosin (H&E) and immunohistochemistry (IHC;
      S100, HMB-45, melanA, and tyrosinase). The other half was analyzed by a nested RT
      PCR assay for tyrosinase. RESULTS: Patients were followed for recurrence with a
      mean follow-up of 71.1 months. The odds ratio of recurrence for RT-PCR positive
      versus RT-PCR negative patients was 1.39 (0.34, 5.62; p = 0.73). Within the
      histology negative subgroups, the risk of recurrence in the RT-PCR positive group
      (26.7%) was not significantly different from the risk of recurrence in the RT-PCR
      negative group (22.2%) (p = 0.33 chi-squared). RT-PCR of the sentinel node was
      not a predictor for recurrence on multivariate analysis (p = 0.65). CONCLUSION:
      Sentinel node RT-PCR positivity did not risk stratify histologically negative
      melanoma patients beyond routine pathologic examination in this series.

PMID- 17219389
TI  - Fetal and maternal MTHFR C677T genotype, maternal folate intake and the risk of
      nonsyndromic oral clefts.
AB  - The association between maternal folate intake and risk of nonsyndromic oral
      clefts has been studied among many populations with conflicting results. The
      methylenetetrahydrofolate reductase gene (MTHFR) plays a major role in folate
      metabolism, and several polymorphisms, including C677T, are common in European
      populations. Data from a French study (1998-2001) let us investigate the roles of
      maternal dietary folate intake and the MTHFR polymorphism and their interaction
      on the risk of cleft lip with/without cleft palate (CL/P) and cleft palate only
      (CP). We used both case-control (164 CL/P, 76 CP, 236 controls; 148, 59, 168 of
      whom, respectively, had an available genotype) and case-parent (143 CL/P and 56
      CP families) study designs and distinguished the role of the child's genotype and
      maternally mediated effects on risks. This study observed a beneficial effect of
      mothers' dietary folate intake on their offspring's risk (odds ratio (OR)(< or =
      230 microg/day) = ref; for CL/P, OR([230-314 microg/day]) = 0.56, 95% confidence
      interval = 0.3-0.9, OR(>314 microg/day) = 0.64, 0.4-1.1; for CP, OR([230-314
      microg/day]) = 1.15, 0.6-2.2, OR(>314 microg/day) = 0.70, 0.3-1.4). We observed a
      reduced risk associated with the TT genotype of the child in the case-control
      analysis (OR(CC) = ref; for CL/P, OR(TT) = 0.54, 0.3-1.1; for CP, OR(TT) = 0.33,
      0.1-1.0); this genotype, either fetal or maternal, was not statistically
      significant in the case-parent analysis. A frequency of TT genotype higher in our
      control group than previously reported in France can partly explain the risk
      reduction observed in case-control comparison. Interactions were not
      statistically significant. Stratified case-parent analysis showed, however,
      slight heterogeneity in the role of TT genotype according to folate intake. The
      modest sample size limits this study, which nonetheless provides new estimate of
      the possible impact of dietary folate intake and MTHFR polymorphism on oral
      clefts.

PMID- 17219390
TI  - Hypoparathyroidism[corrected]-retardation-dysmorphism (HRD): is there a new
      variant not caused by a TBCE mutation?

PMID- 17219391
TI  - Prenatal manifestation of pancytopenia in Pearson marrow-pancreas syndrome caused
      by a mitochondrial DNA deletion.

PMID- 17219392
TI  - A new case of de novo 11q duplication in a patient with normal development and
      intelligence and review of the literature.
AB  - A new case of 11q interstitial duplication is reported in a patient with mild
      dysmorphic features but normal development. Chromosome analysis revealed a de
      novo 11q dup(11)(q14.1q21) on G banding and FISH studies. Additional molecular
      genetic studies revealed a similar but more distal duplication at the level of
      11q21q23.1. Previous cases of isolated 11q duplication that overlapped with this
      case were associated with a wide variety of clinical findings and variable
      developmental disability. These cases all included additional material not
      duplicated in this patient. The current case represents the first de novo case of
      11q duplication with normal development suggesting that the segment between
      11q14.1 and 11q21 contains few genes that are dose sensitive. Review of other
      cases that have used conventional cytogenetic resolution studies suggests that
      the band 11q13.5 may contain genes contributing to the developmental disabilities
      in the cases previously reported with proximal 11q duplication. Differences
      between conventional cytogenetic techniques and newer molecular genetic studies
      are expected. These newer techniques will help refine prognosis and counseling
      for families in the future.

PMID- 17219393
TI  - Helicobacter pylori infection, iNOS, and gastric cancer: the impact of another
      possible link.

PMID- 17219394
TI  - Serum cytokine levels in response to hepatic cryoablation.
AB  - BACKGROUND AND OBJECTIVES: Cryogenic treatment sometimes stimulates the immune
      system by releasing intracellular antigens. We evaluated anti-tumor immune
      response by analyzing alterations in serum cytokine levels. METHODS: Percutaneous
      cryosurgery was performed in 13 patients with unresectable tumors. Serum levels
      of interleukin (IL) -4, -6, and -10, tumor necrosis factor (TNF)-alpha, and
      interferon (IFN)-gamma were measured by enzyme-linked immunosorbent assay
      (ELISA). The Th1/Th2 ratio was estimated from the IFN-gamma/IL-4 ratio. RESULTS:
      Levels of serum factors in the immune reaction (IR) group, in which tumor
      necrosis was identified not only in the treated area but also away from the
      treated area, were compared with those in the local effect (LE) group. Serum
      amyloid A (SAA), C-reactive protein (CRP), and IL-6 levels were increased in both
      groups after three treatments. The serum IL-10 level tended to increase with the
      number of treatments. Pretreatment IL-10 levels in the LE group were
      significantly greater than those in the IR group, and the maximum value in the LE
      group (59.5 +/- 13.2 pg/ml) was greater than that in the IR group (47.0 +/- 15.0
      pg/ml). The TNF-alpha level was increased in the IR group. Pretreatment TNF-alpha
      levels and maximum levels in response to treatment were significantly greater in
      the IR group than in the LE group (P = 0.0313). The Th1/Th2 ratio was increased
      in the IR group, and the maximum ratio was significantly greater in the IR group
      than in the LE group. CONCLUSION: It might be possible to evaluate the appearance
      of immune responses to cryosurgery by monitoring serum cytokine levels.

PMID- 17219395
TI  - Germinal mosaicism and familial recurrence of a SOX2 mutation with highly
      variable phenotypic expression extending from AEG syndrome to absence of ocular
      involvement.

PMID- 17219396
TI  - Postresection hepatic failure: successful treatment with liver transplantation.
AB  - Postoperative liver failure (PLF) is a rare but often fatal complication of major
      hepatic resection. Use of orthotopic liver transplantation (OLT) for PLF remains
      undefined. We conducted a retrospective review of 435 patients who underwent
      hepatic resection between 1990 and 2004; 9 of them (2.0%) developed PLF.
      Indications for resection included primary hepatic malignancies (8), colonic
      metastases (2), and echinococcic cyst (1); all resections were multisegmental, 6
      were extended, and 2 were lobectomies. A total of 7 patients underwent OLT at a
      mean of 25 days after resection. Patients developing PLF had significantly lower
      preoperative platelet counts and significant elevations of total bilirubin,
      direct bilirubin, prothrombin time, and international normalized ratio (INR) by
      postoperative day 2. Pathological cirrhosis and extended right lobectomy were
      associated with significantly increased risk of PLF. Following OLT, there were no
      in-hospital deaths, but 1 patient required retransplantation for primary
      nonfunction. Mean survival with and without OLT was 42.2 and 1.4 months,
      respectively (P = 0.03). Following OLT, 1- and 5-yr patient survivals were 88%
      and 40%, respectively; 1- and 5-yr graft survivals were 75% and 34%,
      respectively. In conclusion, patients with low platelets, biopsy-proven
      cirrhosis, or those undergoing extended resection are at increased risk for PLF.
      OLT for PLF has significant morbidity but allows salvage of an otherwise fatal
      condition.

PMID- 17219397
TI  - Role of aromatic amino acids in protein-nucleic acid recognition.
AB  - Statistical analysis of structures from the PBD has been used to examine the role
      that the aromatic amino acids play in protein-nucleic acid recognition. In
      protein-DNA complexes, the residues Phe and His are found to bind selectively to
      the DNA chain--Phe to A and T, and His to T and G. The preferred binding modes
      are identified, and the interactions involving Phe are shown to be important in
      the transcription process. In protein-RNA complexes, Phe is found to occur far
      less often and is instead replaced by Trp, which binds selectively to C and G,
      offering a possible mechanism for differentiation between the two nucleic acids.
      SASA analysis of the two sets of complexes suggests that all of the aromatic
      amino acids are more heavily involved in binding than would be expected on the
      balance of probability. Phe and Tyr occur approximately equal in both sets of
      data, whereas the proportions of His and Trp vary considerably, supporting the
      idea that these residues may be involved in differentiating between the two
      nucleic acids.

PMID- 17219398
TI  - Optimism and life events as predictors of fear appraisals in mothers of children
      undergoing hematopoietic stem cell transplantation.
AB  - Although mothers' fear appraisals about their child's future health and well
      being affect their own psychological adjustment to their child's hematopoietic
      stem cell transplantation (HSCT), little is known about antecedents of maternal
      fear appraisals. This longitudinal study investigated several potential
      antecedents of these fear appraisals: maternal optimism, recent negative life
      events, lifetime history of traumatic events, and medical characteristics of the
      child's disease and HSCT course. One hundred-forty mothers were interviewed
      during their child's hospitalization for HSCT and at 3-and 6-months post-HSCT.
      Structural equation modeling was used to test a model of hypothesized relations.
      Consistent with predictions, lower optimism and a greater number of negative life
      events were independently associated with greater maternal fear appraisals.
      Contrary to expectations, lifetime history of trauma was not associated with
      maternal fear appraisals. Mothers' fear appraisals during their child's
      hospitalization were, in turn, associated with their fear appraisals up to 6
      months later. These data identify a subset of mothers who may be particularly in
      need of an intervention to increase optimistic coping strategies, improve coping
      with negative life events, and reduce fear appraisals to improve their adjustment
      following their child's HSCT.

PMID- 17219399
TI  - Passive coping and psychological distress in women adhering to regular breast
      cancer surveillance.
AB  - Since 2000 the MRISC study evaluates the psychological consequences of regular
      breast cancer surveillance for women at increased risk for hereditary breast
      cancer. Coping style may influence these psychological consequences. In a cohort
      of 357 women at increased risk for hereditary breast cancer, the impact of coping
      styles on the course, divided into level and trend of psychological distress
      (general and breast cancer specific) was examined, around two consecutive
      surveillance appointments. With structural equation modelling we found passive
      coping to be associated with higher levels of both general and breast cancer
      specific distress. Seeking social support, expression of emotions and thinking
      comforting thoughts were associated with lower levels of psychological distress.
      Coping style was not associated with the trend of psychological distress around
      the two surveillance appointments. It is recommendable to take coping styles into
      account when counselling these high-risk women.

PMID- 17219400
TI  - Bladder outlet obstruction index and maximal flow rate during urodynamic study as
      powerful predictors for the detection of urodynamic obstruction in women.
AB  - AIMS: To evaluate whether bladder outlet obstruction index (BOOI), a mathematical
      index of outlet resistance, in association with maximal flow rate (Qmax) obtained
      during multichannel urodynamics (UDS) or detrusor pressure at maximal flow rate
      (PdetQmax) could help the identification of obstruction in women. METHODS: From
      January 2004 to February 2005, 401 women were assessed in our urodynamic unit. Of
      these, 133 were neurologically intact women, referred symptoms suggestive of
      voiding disorders and had an abnormal non-intubated uroflussometry (NIF) (BOO
      group). A normal NIF was defined as a bell-shaped curve in presence of a Qmax >15
      ml/sec and a PVR <50 ml. Symptoms of voiding disorders were ascertained by
      interview and rated positive if they occurred more than occasionally. Thirty
      seven women were enrolled as unobstructed if they presented a normal NIF and
      symptoms suggestive of voiding disorders less than occasionally (unobstructed
      group). RESULTS: ROC curve demonstrated similar diagnostic accuracy in the
      diagnosis of urodynamic obstruction for Qmax obtained during UDS (AUC = 0.908; P
      < 0.0001; CI99% = 0.831 to 0.985) and BOOI (AUC = 0.879; P < 0.0001; CI99% =
      0.794 to 0.918) and the least was seen for PdetQmax (AUC = 0.706; P = 0.001;
      CI99% = 0.620 to 0.830). A Qmax obtained during UDS cut-off < or =15 ml/sec
      provides specificity of 85.9% and sensitivity of 78.9%. A BOOI cut-off > or = -8
      provides a sensitivity of 80.8% and specificity of 86.1%. The weakest sensitivity
      (64.2%) and specificity (64.6%) was recorded for PdetQmax > or =28 cmH(2)O.
      CONCLUSIONS: BOOI and Qmax obtained during UDS appears to be the most
      discriminating urodynamic parameters of female BOO. The use of these cutoff might
      facilitate the identification of women with functional and anatomical
      obstruction.

PMID- 17219401
TI  - Selective expression of Bhlhb5 in subsets of early-born interneurons and late
      born association neurons in the spinal cord.
AB  - Accumulating evidence has suggested that the basic helix-loop-helix transcription
      factors play important roles in controlling neuronal fate specification and
      differentiation in the developing central nervous system. In this study, we
      report a detailed immunological study on the expression of Bhlhb5 in embryonic
      mouse spinal cord with a newly developed antibody. At the early stage of neural
      development, Bhlhb5 is specifically expressed in dI6 dorsal interneurons and in
      V1 and V2 ventral interneurons. At late stages of development, Bhlhb5 expression
      is detected in a subset of late-born dorsal association interneurons that migrate
      into the uppermost layer of the dorsal horn.

PMID- 17219402
TI  - fgf1 is required for normal differentiation of erythrocytes in zebrafish
      primitive hematopoiesis.
AB  - Hematopoiesis in vertebrate development involves an embryonic, primitive wave and
      a later, definitive wave in which embryonic blood cells are replaced with adult
      blood cells. We here show that zebrafish fgf1 is involved in vivo in primitive
      hematopoiesis. Fibroblast growth factor-1 (FGF1) morpholino knockdown leads to
      abnormal accumulation of blood cells in the posterior intermediate cell mass at
      32 hr postfertilization. Expression of the erythroid markers gata1 and ika,
      normally diminishing in differentiating erythrocytes at this stage, is maintained
      at abnormally high levels in primitive blood cells. The onset of erythrocyte
      differentiation as assessed by o-dianisidine staining is severely delayed. Most
      fgf1 morphants later recover to wild-type appearance, and primitive erythrocytes
      eventually differentiate. Zebrafish fgf1 is syntenic to human FGF1, which maps to
      a critically deleted region in human del(5q) syndrome posing an increased risk of
      leukemia to patients. As its knockdown in zebrafish changes expression of gata1,
      a gene involved in hematopoietic stem cell decisions, FGF1 should be considered
      to play a role in the pathogenesis of del(5q) syndrome.

PMID- 17219403
TI  - Estimation of the period prevalence of inflammatory bowel disease among nine
      health plans using computerized diagnoses and outpatient pharmacy dispensings.
AB  - BACKGROUND: There are few contemporary estimates of prevalence rates for
      inflammatory bowel disease (IBD) in diverse North American communities. METHODS:
      We estimated the period prevalence of IBD for January 1, 1999, through June 30,
      2001, among 1.8 million randomly sampled members of nine integrated healthcare
      organizations in the US using computerized diagnoses and outpatient
      pharmaceutical dispensing. We also assessed the positive predictive value (PPV)
      and sensitivities of 1) the case-finding algorithm, and 2) the 30-month sampling
      period using medical chart review and linkage to a 78-month dataset,
      respectively. RESULTS: The PPV of the case-finding algorithm was 81% (95%
      confidence interval [CI], 78-87) and 84% (95% CI, 79-89) in two different
      organizations. In both, the sensitivity of the optimal algorithm, compared with
      the most inclusive, exceeded 90%. The sensitivity of the 30-month sampling period
      compared with 78 months was 61% (95% CI, 57-64) in one organization. Applying a
      slightly more sensitive case-finding algorithm, the average period prevalence of
      IBD across the nine organizations, standardized to the age- and gender
      distribution of the US population, 2000 census, was 388 cases (95% CI, 378-397)
      per 100,000 persons (range 209-784 per 100,000; average follow-up 26 months). The
      prevalence of Crohn's disease, ulcerative colitis, and unspecified IBD was 129,
      191, and 69 per 100,000, respectively. CONCLUSIONS: The observed average
      prevalence was similar to prevalence proportions reported for other North
      American populations (369-408 per 100,000). Additional research is needed to
      understand differences in the occurrence of IBD among diverse populations as well
      as practice variation in diagnosis and treatment of IBD.

PMID- 17219404
TI  - Fatty acid-induced defects in insulin signalling, in myotubes derived from
      children, are related to ceramide production from palmitate rather than the
      accumulation of intramyocellular lipid.
AB  - The elevation of free fatty acids (FFAs), observed in childhood obesity results
      in intramyocellular lipid (IMCL) accumulation with consequent insulin resistance.
      Using in vitro differentiated myotubes from normal weight pre-pubertal children
      (n = 8), we examined the effects of saturated (palmitate) and unsaturated
      (oleate) FFAs on insulin-stimulated AKT phosphorylation (pAKT) and IMCL
      accumulation. Palmitate decreased pAKT (Mean [SEM] % change pAKT with palmitate
      750 microM vs. control; pThr308 site -50.5% [28.7] and pSer473 site -38.7%
      [11.7]; P < 0.001) with no effect on IMCL formation. Equimolar bromopalmitate did
      not effect pAKT and blocking ceramide production abolished the palmitate-induced
      reduction in signalling, suggesting that ceramide synthesis is critical for
      palmitate's actions. Oleate did not effect pAKT (1,000 microM oleate; pSer473
      site -3.4% [11.4]; P = NS) but increased IMCL accumulation (+32.3% [7.1%]; P <
      0.001). Co-administration of oleate diminished the reduction in pAKT seen with
      palmitate (+36.4% [23.6] vs. -13.3% [13.6]; P = 0.28), with similar IMCL levels
      to oleate alone. Co-administration also caused a significant reduction in 14C
      ceramide synthesis from 14C-palmitate (101.6 [21.6] vs. 371.5 [122.4] DPM/mg
      protein; P < 0.001). In summary, palmitate appears to cause insulin resistance in
      children's myotubes via its metabolism to ceramide, and this process appears
      unrelated to IMCL formation and is ameliorated by oleate.

PMID- 17219405
TI  - Downregulation of TLR4-dependent ATP production is critical for estrogen-mediated
      immunoprotection in Kupffer cells following trauma-hemorrhage.
AB  - Toll-like receptor 4 (TLR4) mediates mitochondrial DNA (mtDNA) damage and
      biogenic responses. Mitochondrial transcription factor A (Tfam) is an essential
      regulator for mtDNA transcription and ATP production. Increased ATP levels were
      associated with normalization of immune function following trauma-hemorrhage.
      Moreover, administration of 17beta-estradiol following trauma-hemorrhage
      upregulates cardiac Tfam and ATP levels. We therefore hypothesized that the
      salutary effect of 17beta-estradiol on Kupffer cell function following trauma
      hemorrhage is mediated via negative regulation of TLR4, which downregulates iNOS,
      upregulates Tfam and mtDNA-encoded gene cytochrome c oxidase I (mtCOI), and
      consequently increases cellular ATP levels. Male C3H/HeN, C3H/HeOuJ (intact
      TLR4), and C3H/HeJ (TLR4 mutant) mice were subjected to trauma-hemorrhage (mean
      BP 35 +/- 5 mmHg approximately 90 min, then resuscitation) or sham operation. At
      the beginning of resuscitation, mice received 17beta-estradiol (25 microg/25 g)
      or vehicle intravenously and were sacrificed 2 h thereafter. Kupffer cell TLR4,
      iNOS, IL-6 and TNF-alpha production capacities were increased, and ATP, Tfam, and
      mtCOI levels were decreased following trauma-hemorrhage. Administration of 17beta
      estradiol following trauma-hemorrhage prevented the increase in Kupffer cell
      TLR4, iNOS, and cytokine production. This was accompanied by normalized ATP,
      Tfam, and mtCOI levels. Furthermore, the decreased Kupffer cell ATP and mtCOI
      levels were not observed in TLR4 mutant mice following trauma-hemorrhage. Taken
      together, these findings suggest that downregulation of TLR4-dependent ATP
      production is critical to 17beta-estradiol-mediated immunoprotection in Kupffer
      cells following trauma-hemorrhage.

PMID- 17219406
TI  - Regulation of PDGF-stimulated SHIP2 tyrosine phosphorylation and association with
      Shc in 3T3-L1 preadipocytes.
AB  - In 3T3-L1 and human preadipocytes, insulin results in the isolated rise in
      phosphatidylinositol (PI)-3,4,5-P3, whereas PDGF produces PI(3,4)P2 in addition
      to PI(3,4,5)P3. SH2 domain-containing inositol 5-phosphatase 2 (SHIP2) converts
      PI(3,4,5)P3 into PI(3,4)P2. PDGF, but not insulin, stimulates SHIP2 tyrosine
      phosphorylation and its association with Shc in human and 3T3-L1 preadipocytes.
      We now demonstrate that SHIP2 tyrosine phosphorylation and association with Shc
      in PDGF-treated 3T3-L1 preadipocytes was reduced by bisindolylmaleimide I (BisI),
      an inhibitor of conventional/novel protein kinase C (PKC). However, the
      production of PI(3,4)P2 and PI(3,4,5)P3 by PDGF was unaffected by BisI.
      Activation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) was not
      sufficient to induce SHIP2 tyrosine phosphorylation. Furthermore, we identified
      threonine 958 (T958) as a novel PDGF-responsive SHIP2 phosphorylation site.
      Mutation of T958 to alanine reduced PDGF-stimulated SHIP2 tyrosine
      phosphorylation and association with Shc, but did not alter its anti
      proliferative effect on preadipocytes. This study demonstrates that SHIP2
      tyrosine phosphorylation and Shc association can be regulated by serine/threonine
      signaling pathways, either indirectly (via PKC), or directly (via T958).
      Interestingly, the anti-proliferative effect of SHIP2 T958A, as well as another
      SHIP2 mutant (Y986F, Y987F) that also displays defective tyrosine phosphorylation
      and Shc association, does not depend on these molecular events.

PMID- 17219407
TI  - Classical Xenopus laevis progesterone receptor associates to the plasma membrane
      through its ligand-binding domain.
AB  - During the last decade, considerable evidence is accumulating that supports the
      view that the classic progesterone receptor (xPR-1) is mediating Xenopus laevis
      oocyte maturation through a non-genomic mechanism. Overexpression and depletion
      of oocyte xPR-1 have been shown to accelerate and to block progesterone-induced
      oocyte maturation, respectively. In addition, rapid inhibition of plasma membrane
      adenylyl cyclase (AC) by the steroid hormone, supports the idea that xPR-1 should
      be localized at the oocyte plasma membrane. To test this hypothesis, we
      transiently transfected xPR-1 cDNA into Cos-7 cells and analyzed its subcellular
      distribution. Through Western blot and immunofluorescence analysis, we were able
      to detect xPR-1 associated to the plasma membrane of transfected Cos-7 cells.
      Additionally, using Progesterone-BSA-FITC, we identified specific progesterone
      binding sites at the cell surface of xPR-1 expressing cells. Finally, we found
      that the receptor ligand-binding domain displayed membrane localization, in
      contrast to the N-terminal domain, which expressed in similar levels, remained
      cytosolic. Overall, these results indicate that a fraction of xPR-1 expressed in
      Cos-7 cells, associates to the plasma membrane through its LBD.

PMID- 17219408
TI  - Tiam1 and betaPIX mediate Rac-dependent endothelial barrier protective response
      to oxidized phospholipids.
AB  - Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC)
      exhibits potent barrier protective effects on pulmonary endothelium, which are
      mediated by small GTPases Rac and Cdc42. However, upstream mechanisms of OxPAPC
      induced small GTPase activation are not known. We studied involvement of
      Rac/Cdc42-specific guanine nucleotide exchange factors (GEFs) Tiam1 and betaPIX
      in OxPAPC-induced Rac activation, cytoskeletal remodeling, and barrier protective
      responses in the human pulmonary endothelial cells (EC). OxPAPC induced membrane
      translocation of Tiam1, betaPIX, Cdc42, and Rac, but did not affect intracellular
      distribution of Rho and Rho-specific GEF p115-RhoGEF. Protein depletion of Tiam1
      and betaPIX using siRNA approach abolished OxPAPC-induced activation of Rac and
      its effector PAK1. EC transfection with Tiam1-, betaPIX-, or PAK1-specific siRNA
      dramatically attenuated OxPAPC-induced barrier enhancement, peripheral actin
      cytoskeletal enhancement, and translocation of actin-binding proteins cortactin
      and Arp3. These results show for the first time that Tiam1 and betaPIX mediate
      OxPAPC-induced Rac activation, cytoskeletal remodeling, and barrier protective
      response in pulmonary endothelium.

PMID- 17219409
TI  - ANG II-stimulated DNA synthesis is mediated by ANG II receptor-dependent
      Ca(2+)/PKC as well as EGF receptor-dependent PI3K/Akt/mTOR/p70S6K1 signal
      pathways in mouse embryonic stem cells.
AB  - Effect of angiotensin II (ANG II) on mouse embryonic stem (ES) cell proliferation
      was examined. ANG II increased [(3)H] thymidine incorporation in a time- (>4 h)
      and dose- (>10(-9) M) dependent manner. The ANG II-induced increase in [(3)H]
      thymidine incorporation was blocked by inhibition of ANG II type 1 (AT(1))
      receptor but not by ANG II type 2 (AT(2)) receptor, and AT(1) receptor was
      expressed. ANG II increased inositol phosphates formation and [Ca(2+)](i), and
      translocated PKC alpha, delta, and zeta to the membrane fraction. Consequently,
      the inhibition of PLC/PKC suppressed ANG II-induced increase in [(3)H] thymidine
      incorporation. The inhibition of EGF receptor kinase or tyrosine kinase prevented
      ANG II-induced increase in [(3)H] thymidine incorporation. ANG II phosphorylated
      EGF receptor and increased Akt, mTOR, and p70S6K1 phosphorylation blocked by AG
      1478 (EGF receptor kinase blocker). ANG II-induced increase in [(3)H] thymidine
      incorporation was blocked by the inhibition of p44/42 MAPKs but not by p38 MAPK
      inhibition. Indeed, ANG II phosphorylated p44/42 MAPKs, which was prevented by
      the inhibition of the PKC and AT(1) receptor. ANG II increased c-fos, c-jun, and
      c-myc levels. ANG II also increased the protein levels of cyclin D1, cyclin E,
      cyclin-dependent kinase (CDK) 2, and CDK4 but decreased the p21(cip1/waf1) and
      p27(kip1), CDK inhibitory proteins. These proteins were blocked by the inhibition
      of AT(1) receptor, PLC/PKC, p44/42 MAPKs, EGF receptor, or tyrosine kinase. In
      conclusion, ANG II-stimulated DNA synthesis is mediated by ANG II receptor
      dependent Ca(2+)/PKC and EGF receptor-dependent PI3K/Akt/mTOR/p70S6K1 signal
      pathways in mouse ES cells.

PMID- 17219410
TI  - Versican modulates gap junction intercellular communication.
AB  - Versican is a large chondroitin sulfate proteoglycan and belongs to the family of
      lecticans. Versican possesses two globular domains, G1 and G3 domain, separated
      by a CS-attachment region. The CS-attachment region present in the middle region
      is divided into two spliced domains named CSalpha and beta. Alternative splicing
      of versican generates at least four versican isoforms named V0, V1, V2, and V3.
      We have successfully cloned the full-length cDNA of chick versican isoforms V1
      and V2 and found that versican isoform V1 induced mesenchymal-epithelial
      transition in NIH3T3 cells. Mesenchymal-epithelial transition induced by V1 in
      NIH3T3 cells is characterized by expression of E-cadherin and occludin, two
      epithelial markers, and reduced expression of fibroblastic marker vimentin (Sheng
      et al., 2006, Mol Biol Cell. 17, 2009-2020). In the present studies, we found
      that versican V1 isoform not only induced cell transition, but also increased
      intercellular communication via gap junction channels composed of connexin
      proteins. Our results showed that V1 induces plasma membrane localization of
      connexin 43, resulting in increased cell communication. This was further
      confirmed by blocking assays. Gap junctions mediated the transfer of small
      cytoplasmic molecules and the diffusion of second messenger molecules between
      adjacent cells. The ability of versican in regulating gap junction implied a
      potential role of versican in coordinating functions.

PMID- 17219411
TI  - Amelioration of inflammation, angiogenesis and CTGF expression in an arthritis
      model by a TSP1-derived peptide treatment.
AB  - OBJECTIVE: To evaluate the effect of a thrombospondin 1 (TSP1)-derived peptide on
      inflammation and angiogenesis in an animal model of erosive arthritis and to
      assess the relationship between TSP1 and connective tissue growth factor (CTGF)
      in the pathophysiology of rheumatoid arthritis. METHODS: Erosive arthritis in
      Lewis rats was induced by peptidoglycan-polysaccharide (PG-PS). Animals were
      divided into four groups: (1) negative control and groups receiving, (2) no
      treatment, (3) treatment with a TSP1-derived peptide, and (4) treatment with a
      scrambled peptide. Samples obtained from ankle joint, spleen and liver were
      studied using histology, histomorphometry, immunohistochemistry and RT-PCR.
      RESULTS: Histological data indicated that the TSP1-derived peptide treatment
      decreased neovascularization, leukocyte infiltration and thickening of the
      synovial lining of the joint, and reduced granuloma formation in the spleen and
      liver when compared to control groups. Higher concentrations of CTGF and TSP1
      proteins were observed in the affected areas of animals which did not receive
      TSP1-derived peptide treatment. Also, immunofluorescence and RT-PCR analyses
      showed an increase in CTGF protein expression and regulation, respectively, in
      the tissues of untreated animals when compared to the TSP1-derived peptide
      treated animals. By immunofluorescence, TSP1 expression was decreased in the TSP1
      derived peptide treated animals. Moreover, macrophage/monocyte-specific staining
      revealed a decrease in cell infiltration in the articular tissue of the TSP1
      derived peptide treated animals. CONCLUSION: Both inflammation and angiogenesis
      were decreased after TSP1-derived peptide treatment indicating a potential
      pathway by which TSP1 interaction with neutrophils induces CTGF in RA affected
      tissues.

PMID- 17219412
TI  - Activation of caspase-8 and Erk-1/2 in domes regulates cell death induced by
      confluence in MDCK cells.
AB  - Under normal culture conditions, cells adhere to culture dish, spread out,
      proliferate, and finally cover all areas and reach confluence. During the
      confluent stage, cell proliferation ceases and differentiation is enhanced.
      Meanwhile, cell death also appears as the monolayer confluence proceeds. To
      delineate the mechanism of cell death induced by the confluent process, we
      employed Madin-Darby canine kidney (MDCK) cells. When approaching confluence,
      MDCK cells exhibited increase the levels of caspase-2 and enhanced the activity
      of caspase-8. Using various caspase inhibitors to block apoptosis, we found that
      only z-VAD-fmk and z-IETD-fmk can inhibit confluent cell death, indicating that
      confluent cell death is mediated by activation of caspase-8. Overexpression of
      Bcl-2 inhibited confluent cell death, suggesting the involvement of mitochondria
      dependent pathway in confluent cell death. Interestingly, the activity of phospho
      Erk (p-Erk) was initially decreased before confluence, but markedly increased
      after confluence. Immunofluorescence staining studies showed that p-Erk was
      expressed exclusively on dome-forming cells that underwent apoptosis. Treatment
      of confluent MDCK cells with PD98059 and UO126, the inhibitors of MEK, enhanced
      apoptosis as well as activity of caspase-8. These data indicate that elevation of
      p-Erk activity during confluence may serve to suppress confluent cell death.
      Taken together, activation of caspase-8 contributes to and results in confluent
      cell death, whereas elevated p-Erk activity serves to prevent confluent cell
      death by regulating activation of caspase-8.

PMID- 17219413
TI  - Activating transcription factor 2 controls Bcl-2 promoter activity in growth
      plate chondrocytes.
AB  - Activating transcription factor 2 (ATF-2) is expressed ubiquitously in mammals.
      Mice deficient in ATF-2 (ATF-2 m/m) are slightly smaller than their normal
      littermates at birth. Approximately 50% of mice born mutant in both alleles die
      within the first month. Those that survive develop a hypochondroplasia-like
      dwarfism, characterized by shortened growth plates and kyphosis. Expression of
      ATF-2 within the growth plate is limited to the resting and proliferating zones.
      We have previously shown that ATF-2 targets the cyclic AMP response element (CRE)
      in the promoters of cyclin A and cyclin D1 in growth plate chondrocytes to
      activate their expression. Here, we demonstrate that Bcl-2, a cell death
      inhibitor that regulates apoptosis, is expressed within the growth plate in
      proliferative and prehypertrophic chondrocytes. However, Bcl-2 expression
      declines in hypertrophic chondrocytes. The Bcl-2 promoter contains a CRE at 
      1,552 bp upstream of the translation start. Mutations within this CRE cause
      reduced Bcl-2 promoter activity. We show here that the absence of ATF-2 in growth
      plate chondrocytes corresponds to a decline in Bcl-2 promoter activity, as well
      as a reduction in Bcl-2 protein levels. In addition, we show that ATF-2 as well
      as CREB, a transcription factor that can heterodimerize with ATF-2, bind to the
      CRE within the Bcl-2 promoter. These data identify the Bcl-2 gene as a novel
      target of ATF-2 and CREB in growth plate chondrocytes.

PMID- 17219414
TI  - DNA methylation and immunohistochemical analysis of the S100A4 calcium binding
      protein in human prostate cancer.
AB  - BACKGROUND: The role of DNA methylation in the transcriptional regulation of
      S100A4 is unknown in human prostate cancer. METHODS: Critical CpG sites within
      intron 1 of S100A4 were sequenced in DNA obtained from prostatic adenocarcinoma,
      non-malignant epithelium, and prostate cancer cell lines. S100A4 protein
      expression was assessed by immunohistochemistry and Western blotting. RESULTS:
      Methylation was seen in all cases of cancer, non-malignant epithelium, and in
      prostate cancer cell lines, but was absent in all cases of blood DNA. S100A4
      immunoexpression was absent in all cases of malignant and non-malignant
      epithelium, while strong-moderate expression was seen in the stroma and
      lymphocytes. Western blotting showed absent S100A4 expression in LNCaP and Du145
      cells and low levels in PC-3 cells. CONCLUSIONS: S100A4 protein is not expressed
      in benign or malignant prostatic epithelium nor in LNCaP and Du145 cells. The
      mechanism underlying absent S100A4 expression in prostatic epithelium and cell
      lines may involve methylation.

PMID- 17219415
TI  - Cyclooxygenase-2 expression is critical for chronic UV-induced murine skin
      carcinogenesis.
AB  - While it has been established that both the constitutive and inducible forms of
      cyclooxygenase (COX-1 and COX-2, respectively) play important roles in chemical
      initiation-promotion protocols with phorbol ester tumor promoters, the
      contribution of these two enzymes to ultraviolet (UV) light-induced skin tumors
      has not been fully assessed. To better understand the contribution of COX-1 and
      COX-2 to UV carcinogenesis, we transferred the null allele for each isoform onto
      the SKH-1 hairless strain of mouse. Due to low viability on this background with
      complete knockout of COX-2, heterozygous mice were used in UV carcinogenesis
      experiments. While the lack of one allele of COX-1 had no effect on tumor
      outcome, the lack of one allele of COX-2 resulted in a 50-65% reduction in tumor
      multiplicity and a marked decrease in tumor size. Additionally, transgenic SKH-1
      mice that overexpress COX-2 under the control of a keratin 14 promoter developed
      70% more tumors than wild-type SKH-1 mice. The lack of one allele of either COX-1
      or COX-2 reduced prostaglandin (PG) E2 levels in response to a single UV
      treatment. The proliferative response to UV was significantly reduced in COX-2,
      but not COX-1, heterozygous mice. UV-induced apoptosis, however, was greater in
      COX-2 heterozygous mice. Collectively, these results clearly establish the
      requirement for COX-2 in the development of skin tumors.

PMID- 17219416
TI  - Mouse skin chemical carcinogenesis is inhibited by antizyme in promotion
      sensitive and promotion-resistant genetic backgrounds.
AB  - Elevated polyamine content and increased ornithine decarboxylase (ODC) activity
      have been associated with neoplastic growth in numerous animal models and human
      tissues. Antizyme (AZ) is a negative regulator of polyamine metabolism that
      inhibits ODC activity, stimulates ODC degradation, and suppresses polyamine
      uptake. Preliminary evidence, obtained from transgenic mice with tissue specific
      overexpression of AZ indicates that tumor development can be suppressed by AZ. To
      extend these studies, we have examined the effect of keratin 5 (K5)- or K6-driven
      AZ transgenes on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol
      13-acetate (TPA) chemical carcinogenesis of the skin, in promotion-resistant
      C57BL/6 and promotion-sensitive DBA/2 mice. On both genetic backgrounds, K6-AZ
      mice showed a reduction in tumor multiplicity, with 85% fewer tumors than wild
      type controls on the C57BL/6 background and 50% fewer tumors on the DBA/2
      background. K5-AZ mice developed 50% fewer tumors than controls on both
      backgrounds. The percent of mice with tumors and tumor size were also reduced in
      the K5-AZ and K6-AZ groups. Tumor and TPA-treated skin sections from K6-AZ mice
      exhibited the strongest AZ expression, with localization mainly in suprabasal
      keratinocytes. K6-AZ mice also had slightly reduced cell proliferation rates in
      tumors and TPA-treated skin. The lack of a more pronounced effect on cell
      proliferation is probably explained by the observation that AZ staining did not
      colocalize with proliferating cell nuclear antigen (PCNA), a marker for the
      proliferative compartment. These studies demonstrate a tumor-suppressive effect
      of AZ in C57BL/6 and DBA/2 mice, and confirm the importance of ODC and polyamines
      in tumor development.

PMID- 17219417
TI  - Potentiation of chemotherapeutics by the Hsp90 antagonist geldanamycin requires a
      steady serum condition.
AB  - Inhibition of Hsp90 potentiates diverse chemotherapeutics, but it is not clear if
      this applies only to specific agents, tumor types or conditions. The aim of this
      report is to determine the effect of serum starvation (SS) on potentiation. SUIT2
      cells were cultured with and without the presence of serum and 3-[4,5
      dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays were carried
      out at time intervals. Cytotoxic agents were added individually or in
      combination. Immunohistochemistry of tumor samples and immunofluorescence of
      cultured cells were used to examine Hsp90 localization. In the presence of serum
      an at least additive effect of combining the Hsp90 inhibitor geldanamycin (GA)
      with 5-fluorouracil (5FU) was demonstrated. Following pretreatment with GA, 5FU
      and GA were synergistic. However, during SS GA was protective against 5FU.
      Geldanamycin also protected cells from 12-O-tetradecanoylphorbol-13-acetate (TPA)
      during SS. Protection of cells is transitory, as after 24 h of SS GA again has an
      at least additive negative effect on vitality with 5FU or TPA. Serum starvation
      of pancreatic cancer cell lines causes normally largely cytoplasmic Hsp90 to
      become predominantly nuclear localized. Hsp90 nuclear localization was observed
      in pancreatic and prostate tumors. Hsp90 binding to a pro-apoptotic client could
      explain the transitory protection of cells by Hsp90 inhibition during SS.
      Although potentiation of chemotherapeutics by Hsp90 inhibition is probably a
      general phenomenon, design of clinical trials should take into account that
      continuous co-administration may be ineffective because of a balance of synergy
      of the drugs in some cells and mutual inhibition of the two drug activities in
      other cells.

PMID- 17219418
TI  - Altered mRNA expression patterns in bovine blastocysts after fertilisation in
      vitro using flow-cytometrically sex-sorted sperm.
AB  - Sperm-sexing has been used to produce embryos and offspring of a pre-determined
      sex in a number of species. However, the fertility of sex-sorted sperm is reduced
      and the full effects of sperm-sexing remain to be elucidated. The purpose of the
      present study was to investigate the potential effects of sex-sorted sperm on
      mRNA expression patterns of developmentally important genes employing in vitro
      produced bovine embryos. Bovine embryos were produced in vitro with unsorted and
      sex-sorted sperm and mRNA expression patterns were determined for glucose-3
      transporter (Glut-3), glucose-6-phosphate dehydrogenase (G6PD), X-inactive
      specific transcript (X-ist) and Heat shock protein 70.1 (Hsp) using semi
      quantitative endpoint reverse transcriptase-PCR in male and female, day-7 and 8
      embryos. The relative abundance (RA) of Glut-3 was higher for day-7 male than
      female embryos, and day-7 embryos derived from unsorted compared with sex-sorted
      sperm. The RA of G6PD was higher for embryos derived from unsorted than sex
      sorted sperm, and for day-8 female compared with male embryos. The RA of Xist was
      higher for female than male embryos, and for day-7 female embryos derived from
      unsorted than sex-sorted sperm. Hsp RA was higher for female compared with male
      embryos, was similar for day-7 and 8 embryos, and unsorted and sex-sorted sperm
      derived embryos. These results demonstrate differential expression of
      developmentally important genes between male and female embryos, and embryos
      derived from unsorted and sex-sorted sperm.

PMID- 17219419
TI  - Expression of follicle stimulating hormone and luteinizing hormone receptors
      during follicular growth in the domestic cat ovary.
AB  - In order to better understand the pituitary regulation of follicular growth in
      the domestic cat, follicle stimulating hormone (FSH) and luteinizing hormone (LH)
      receptors (R) were localized and quantified in relation to follicle diameter and
      atresia using in situ ligand binding on ovarian sections. Expression of FSHR was
      homogeneous and restricted to follicle granulosa cells from the early antral
      stage onwards, whereas expression of LHR was heterogeneous on theca cells of all
      follicles from the early antral stage onward, and homogeneous on granulosa cells
      of healthy follicles larger than 800 microm in diameter and in corpora lutea. LHR
      were also widely expressed as heterogeneous aggregates in the ovarian
      interstitial tissue. Atretic follicles exhibited significantly reduced levels of
      both FSHR and LHR on granulosa cells, compared with healthy follicles whatever
      the follicular diameter, whereas levels of LHR on theca cells were lower only for
      atretic follicles larger than 1,600 microm in diameter. In healthy follicles,
      levels of FSHR and LHR in all follicular compartments increased significantly
      with diameter. Although generally comparable to that observed in other mammals,
      the expression pattern of gonadotropin receptors in the cat ovary is
      characterized by an early acquisition of LHR on granulosa cells of growing
      follicles and islets of LH binding sites in the ovarian interstitial tissue.

PMID- 17219420
TI  - Suppression of connexin 43 and E-cadherin transcripts in in vitro derived bovine
      embryos following culture in vitro or in vivo in the homologous bovine oviduct.
AB  - In this study, a combination of RNAi and endoscopic transfer to the oviduct of
      synchronized heifers has been used to investigate the effect of suppression of
      Cx43 and E-cadherin on the development, mRNA and protein expression of bovine
      blastocysts cultured in vitro or in vivo. In vitro matured and fertilized bovine
      zygotes were randomly assigned to one of four groups namely: Connexin43 dsRNA
      injected (n = 790), E-cadherin dsRNA-injected (n = 775), water-injected (n =
      774), and noninjected controls (n = 652). Following 2 days in vitro culture, 4-
      and 8-cell stage embryos from each treatment group were used for culture in vitro
      or in vivo. About half of the 4-8-cell stage embryos from each treatment group
      were transferred to the oviduct of synchronized heifers, while the remainder were
      further cultured in vitro. Embryos from in vivo culture were flushed from
      recipients on the fourth day post transfer (= Day 7 post insemination).
      Blastocyst stage embryos from both culture systems were used for mRNA and protein
      expression analysis. Irrespective of treatment or culture conditions,
      microinjection resulted in a decline in the proportion of embryos reaching the
      blastocyst stage. Significantly, lower blastocyst development was observed in E
      cadherin and water-injected embryos following in vivo culture compared to the
      noninjected controls, while intermediate results were obtained following
      injection with Cx43 dsRNA. Both mRNA and protein products of the target genes
      were suppressed but the efficiency of suppression of the target genes varied
      depending on the initial level of transcript abundance, which is known to be
      greatly affected by the culture environment.

PMID- 17219421
TI  - Protein kinase C delta enhances proliferation and survival of murine mammary
      cells.
AB  - Protein kinase C (PKC) delta, a member of the novel family of PKC serine
      threonine kinases, has been implicated in negative regulation of proliferation
      and apoptosis in a large number of cell types, including breast cancer cell
      lines, and postulated as a tumor suppressor gene. In this study we show that in
      murine NMuMG mammary cells PKCdelta promotes a mitogenic response. Overexpression
      of PKCdelta in NMuMG cells leads to a significant increase in [3H]-tymidine
      incorporation and cell proliferation, as well as enhanced extracellular signal
      regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) activation.
      Activation of PKCdelta with a phorbol ester leads to elevated cyclin D1
      expression and an hyperphosphorylated Rb state. Surprisingly, ectopic expression
      of PKCdelta conferred anchorage-independent growth capacity to NMuMG cells.
      PKCdelta overexpressors showed enhanced resistance to apoptotic stimuli, such as
      serum deprivation or doxorubicin treatment, an effect that correlates with
      hyperactivation of the Akt survival pathway. Our results provide evidence for a
      role of PKCdelta as a positive modulator of proliferative and survival signals in
      immortalized mammary cells. The fact that PKCdelta exerts differential responses
      depending on the cell context not only highlights the necessity to carefully
      understand the signaling events controlled by this PKC in each cell type but also
      suggests that we should be cautious in considering this kinase a target for
      cancer therapy.

PMID- 17219422
TI  - Retinol decreases beta-catenin protein levels in retinoic acid-resistant colon
      cancer cell lines.
AB  - The beta-catenin signaling pathway is dysregulated in most cases of colon cancer
      resulting in an accumulation of nuclear beta-catenin and increased transcription
      of genes involved in tumor progression. This study examines the effect of retinol
      on beta-catenin protein levels in three all-trans retinoic acid (ATRA)-resistant
      human colon cancer cell lines: HCT-116, WiDr, and SW620. Each cell line was
      treated with increasing concentrations of retinol for 24 or 48 h. Retinol reduced
      beta-catenin protein levels and increased ubiquitinated beta-catenin in all cell
      lines. Treatment with the proteasomal inhibitor MG132 blocked the retinol-induced
      decrease in beta-catenin indicating retinol decreases beta-catenin by increasing
      proteasomal degradation. Multiple pathways direct beta-catenin to the proteasome
      for degradation including a p53/Siah-1/adenomatous polyposis coli (APC), a
      Wnt/glycogen synthase kinase-3beta/APC, and a retinoid "X" receptor (RXR)
      mediated pathway. Due to mutations in beta-catenin (HCT-116), APC (SW620), and
      p53 (WiDr), only the RXR-mediated pathway remains functional in each cell line.
      To determine if RXRs facilitate beta-catenin degradation, cells were treated with
      the RXR pan-antagonist, PA452, or transfected with RXRalpha small interfering RNA
      (siRNA). The RXR pan-antagonist and RXRalpha siRNA reduced the ability of retinol
      to decrease beta-catenin protein levels. Nuclear beta-catenin induces gene
      transcription via interaction with T cell factor/lymphoid enhancer factor
      (TCF/LEF) proteins. Retinol treatment decreased the transcription of a TOPFlash
      reporter construct and mRNA levels of the endogenous beta-catenin target genes,
      cyclin D1 and c-myc. These results indicate that retinol may reduce colon cancer
      cell growth by increasing the proteasomal degradation of beta-catenin via a
      mechanism potentially involving RXR.

PMID- 17219423
TI  - Association between Aurora-A kinase polymorphisms and age of onset of hereditary
      nonpolyposis colorectal cancer in a Caucasian population.
AB  - Aurora-A kinase is considered a potential cancer susceptibility gene that encodes
      a centrosome-associated, cell cycle-regulated serine/threonine kinase. We studied
      two single nucleotide polymorphisms (SNP) in the coding region of Aurora-A, 91T
      to-A (F31I) and 169G-to-A (V57I). We studied the influence of these two
      polymorphisms on age of onset of hereditary nonpolyposis colorectal cancer
      (HNPCC). Genotyping of the Aurora-A polymorphisms was carried out on 125
      Caucasian with mismatch repair (MMR) gene mutations with real-time pyrophosphate
      DNA sequencing. For the 91T-to-A polymorphism, we found that patients with HNPCC
      who were homozygous for the wild-type allele developed colorectal cancer (CRC) 7
      years earlier than patients who were homozygous or heterozygous for the mutant
      allele. The169G-to-A polymorphism did not have a significant influence on risk
      for HNPCC. However, when we did haplotype analysis for these two polymorphisms,
      the 91A-169G haplotype was associated with protection from HNPCC at an earlier
      age.

PMID- 17219424
TI  - Colorectal carcinoma development in inducible nitric oxide synthase-deficient
      mice with dextran sulfate sodium-induced ulcerative colitis.
AB  - The overproduction of reactive oxygen and nitrogen species (RONS) may play an
      important role in ulcerative colitis (UC)-associated carcinogenesis. In order to
      study the role of nitric oxide (NO) in UC-associated colorectal carcinogenesis,
      the development of colorectal carcinoma was studied using the DSS-induced and
      iron-enhanced model of chronic UC in inducible nitric oxide synthase (iNOS)
      deficient mice. Female wild-type C57BL/6 (iNOS+/+) and iNOS-/- mice were
      administered 1% DSS (w/v) through the drinking fluid for 15 DSS cycles and fed
      twofold iron-enriched diet. Colorectal inflammation and mucosal ulceration of
      moderate severity were observed in both iNOS+/+ and iNOS-/- mice. Similar tumor
      incidence and multiplicity in the colon were observed that 15 out of 23 (65.2%)
      iNOS+/+ mice developed colorectal tumors with a tumor multiplicity of 1.47+/-0.17
      (mean+/-SE) after 15 DSS cycles, and 13 out of 19 (68.4%) iNOS-/- mice developed
      colorectal tumors with a tumor multiplicity of 2.08+/-0.21. Histopathologically,
      the tumors were confirmed to be well-differentiated adenocarcinomas.
      Nitrotyrosine, an indicator of peroxynitrite-caused protein modification, was
      detectable by immunohistochemistry in inflammatory cells and epithelial cells of
      the colon in iNOS+/+ and iNOS-/- mice, and no difference in staining intensity
      was observed between the two groups. Immunostaining for endothelial NOS (eNOS)
      was observed in lamina propria macrophages and colonic blood vessels, and eNOS
      protein levels were increased in the inflamed colon. These results show that
      there is no difference in UC-associated cancer development in iNOS+/+ and iNOS-/-
      mice, and suggest that in the absence of iNOS, other factors, such as eNOS, may
      play a role in nitrosative stress and UC-associated carcinogenesis in this model
      system.

PMID- 17219425
TI  - Atypical localization of membrane type 1-matrix metalloproteinase in the nucleus
      is associated with aggressive features of hepatocellular carcinoma.
AB  - Membrane type 1-matrix metalloproteinase (MT1-MMP) is a versatile proteinase and
      recent studies indicated it could be internalized. Our earlier study found that
      it is overexpressed in hepatocellular carcinoma (HCC) and could promote
      intrahepatic metastasis. The present study was conducted to examine its
      subcellular localization and its clinicopathological significance in HCC after
      curative partial hepatectomy. Localization of MT1-MMP in 101 pairs of HCCs and
      their adjacent liver tissues, and 8 normal liver tissues was examined by the
      immunohistochemical method. MT1-MMP protein was localized at membrane and
      cytoplasm of hepatocytes in the normal and tumor adjacent liver tissues. In
      contrast, the HCCs were highly heterogeneous with variable degrees of membrane,
      cytoplasmic, and even nuclear staining. Interestingly, patients with presence of
      nuclear MT1-MMP were associated with poor overall survival (log-rank test,
      P=0.043) and large tumor size (>5 cm) (Fisher's exact test, P=0.031). Subcellular
      distribution was further demonstrated by Western blotting and immunofluorescence
      with Hep3B stable transfectant overexpressing MT1-MMP. Western blot analyses of
      subcellular fractions confirmed a differential partitioning of various post
      translationally modified MT1-MMP in these fractions. Different antibodies
      corroborated the presence of MT1-MMP in the nuclear fraction. Concomitant nuclear
      presence of MMP2 with MT1-MMP further indicated its potential involvement in the
      nuclear functions. MT1-MMP co-localized with caveolin-1 at the perinuclear
      region, suggesting nuclear translocation of MT1-MMP via caveolae-mediated
      endocytosis. In summary, the association of nuclear MT1-MMP with aggressive tumor
      features including poor prognosis and large tumor expands its functional
      repertoire and further indicates a new functional role of MMPs within nuclei of
      tumor cells.

PMID- 17219426
TI  - Epigenetic reprogramming of liver cells in tamoxifen-induced rat
      hepatocarcinogenesis.
AB  - Tamoxifen, a nonsteroidal anti-estrogen, is a potent genotoxic hepatocarcinogen
      in rats, with both tumor initiating and promoting properties. Recently it has
      been demonstrated that genotoxic carcinogens, in addition to exerting genotoxic
      effects, often cause epigenetic alterations and these induced epigenetic changes
      may play important mechanistic role in carcinogenesis. In the present study, we
      investigated the role of tamoxifen-induced epigenetic changes in
      hepatocarcinogenic process. The results of the study showed that exposure of
      female F344 rats to tamoxifen resulted in progressive loss of CpG methylation in
      regulatory sequences of long interspersed nucleotide elements (LINE-1) and
      prominent increase in expression of LINE-1 elements and c-myc proto-oncogene. The
      accumulation of tamoxifen-induced DNA lesions was accompanied by the decreased
      level of Rad51, Ku70, and DNA polymerase beta (Polbeta) proteins that play a
      crucial role in maintenance of genomic stability. Furthermore, feeding rats with
      tamoxifen-containing diet led to increased regenerative cell proliferation, as
      indicated by the increased level of Ki-67 and proliferating cell nuclear antigen
      (PCNA) proteins. These data indicate that exposure of animals to genotoxic
      hepatocarcinogen tamoxifen led to early phenotypical alterations in livers
      characterized by emergence of epigenetically reprogrammed cells with a specific
      cancer-related epigenetic phenotype prior to tumor formation.

PMID- 17219427
TI  - HnRNP E2 is downregulated in human oral cancer cells and the overexpression of
      hnRNP E2 induces apoptosis.
AB  - Human hnRNP genes have been reported to be involved in human malignancies and
      several hnRNPs are promising biomarkers of lung, head and neck, colon, breast,
      and pancreatic cancers. The present study investigated the clinicopathologic and
      biological significance of hnRNP E2 gene expression in oral cancer. Human hnRNP
      E2 was significantly downregulated in oral cancer tissues compared to normal one
      (P<0.0001) as determined by quantitative real-time reverse transcription PCR. The
      expression of hnRNP E2 is correlated with histology, being lower in moderate and
      poorly differentiated squamous cell carcinoma (SCC) compared to well
      differentiated SCC. Transient transfection of hnRNP E2 in cancerous cell lines
      resulted in reduced cell viability and increased apoptotic nuclei. Compared to
      control transfectants, cells with higher expression showed an increase in the
      number of apoptotic cells by annexin-PI staining and an increase in caspase
      activity. The present study thus implicates downregulation of hnRNP E2 as a novel
      mechanism to enhance the resistance of cancer cells to apoptosis.

PMID- 17219428
TI  - Dominant manifestation of pluripotency in embryonic stem cell hybrids with
      various numbers of somatic chromosomes.
AB  - Developmental potential was assessed in 8 intra-specific and 20 inter-specific
      hybrid clones obtained by fusion of embryonic stem (ES) cells with either
      splenocytes or fetal fibroblasts. Number of chromosomes derived from ES cells in
      these hybrid clones was stable while contribution of somatic partner varied from
      single chromosomes to complete complement. This allowed us to compare
      pluripotency of the hybrid cells with various numbers of somatic chromosomes.
      Three criteria were used for the assessment: (i) expression of Oct-4 and Nanog
      genes; (ii) analyses of teratomas generated by subcutaneous injections of the
      tested cells into immunodeficient mice; (iii) contribution of the hybrid cells in
      chimeras generated by injection of the tested cells into C57BL blastocysts. All
      tested hybrid clones showed expression of Oct-4 and Nanog at level comparable to
      ES cells. Histological and immunofluorescent analyses demonstrated that most
      teratomas formed from the hybrid cells with different number of somatic
      chromosomes contained derivatives of three embryonic layers. Tested hybrid clones
      make similar contribution in various tissues of chimeras in spite of significant
      differences in the number of somatic chromosomes they contained. The data
      indicate that pluripotency is manifested as a dominant trait in the ES hybrid
      cells and does not depend substantially on the number of somatic chromosomes. The
      latter suggests that the developmental potential derived from ES cells is
      maintained in ES-somatic cell hybrids by cis-manner and is rather resistant to
      trans-acting factors emitted from the somatic one.

PMID- 17219429
TI  - Temporal expression of transcripts related to embryo quality in bovine embryos
      cultured from the two-cell to blastocyst stage in vitro or in vivo.
AB  - The post-fertilization embryo culture environment can have a dramatic effect on
      the pattern of gene expression in the embryo and it is widely acknowledged that
      bovine embryos derived from in vitro culture are of inferior quality to those
      derived in vivo. The objective of this study was to examine temporal variation in
      the mRNA abundance of several transcription and translation factors known to
      differ between blastocysts produced following culture in vitro and in vivo.
      Embryos were recovered from two in vitro culture systems SOF1 or SOF2 at five
      developmental stages: 2- to 4-cell, 8-cell, 16-cell, morula, and blastocyst. In
      vivo embryos were produced from superovulated and artificially inseminated
      heifers and recovered at approximately 40 hr or 3, 4, 5, and 7 days
      postinsemination. Blastocysts were also produced following in vitro maturation,
      in vitro fertilization and culture in the ewe oviduct. Analysis of relative
      transcript abundance for FOXO3A, EEF1G, HMG2, and REA was performed using
      quantitative real-time PCR. Irrespective of culture environment each transcript
      followed, approximately the same general pattern of expression where relative
      abundance decreased dramatically from the 2- to 4-cell stage to 8-cell stage and
      increased from the morula to blastocyst stage (P < 0.05). Transcripts for GNBL2
      were not observed between the 2- and 16-cell stage of development. Relatively
      high expression at the 2- to 4-cell indicated that these transcripts are most
      likely of maternal origin produced in the oocyte during growth and final
      maturation. A culture-induced change in mRNA abundance of transcription and
      translation factors was evident in embryos that were produced not only between in
      vivo and in vitro culture environments but also between different in vitro
      culture systems.

PMID- 17219430
TI  - Inactivation of MAPK affects centrosome assembly, but not actin filament
      assembly, in mouse oocytes maturing in vitro.
AB  - Mitogen-activated protein kinase (MAPK) plays a crucial role in meiotic
      maturation of mouse oocytes. In order to understand the mechanism by which MAPK
      regulates meiotic maturation, we examined the effects of the MAPK pathway
      inhibitor U0126 on microtubule organization, gamma-tubulin and nuclear mitotic
      apparatus protein (NuMA) distribution, and actin filament assembly in mouse
      oocytes maturing in vitro. Western blotting with antibodies that detect active,
      phosphorylated MAPK revealed that MAPK was inactive in fully grown germinal
      vesicle (GV) oocytes. Phosphorylated MAPK was first detected 3 hr after the
      initiation of maturation cultures, was fully active at 6 hr, and remained active
      until metaphase II. Treatment of GV stage oocytes with 20 microM U0126 completely
      blocked MAPK phosphorylation, but did not affect GV breakdown (GVBD). However,
      the oocytes did not progress to the Metaphase I stage, which would normally occur
      after 9 hr in the maturation cultures. The inhibition of MAPK resulted in
      abnormal spindles and abnormal distributions of gamma-tubulin and NuMA, but did
      not affect actin filament assembly. In oocytes treated with U0126 after GVBD,
      polar body extrusion was normal, but the organization of the metaphase plate and
      chromosome segregation were abnormal. In conclusion, the meiotic abnormalities
      caused by U0126, a specific inhibitor of MAPK signaling, indicate that MAPK plays
      an important regulatory role in microtubule and centrosome assembly, but not
      actin filament assembly.

PMID- 17219431
TI  - Estrogen-dependent expression of the tissue kallikrein gene (Klk1) in the mouse
      uterus and its implications for endometrial tissue growth.
AB  - Tissue kallikrein mK1 is a serine protease involved in the generation of
      bioactive kinins for normal cardiac and arterial function in the mouse. In the
      present study, the tissue kallikrein gene Klk1, which codes for mK1, was shown to
      be one of the most prevalent of the Klk gene species in the uteri of adult mice,
      and its mRNA level was significantly higher at estrus than at diestrus. Klk1 mRNA
      expression was enhanced in the uteri of ovariectomized mice receiving estradiol
      17beta treatment. Both endometrial epithelial and stromal cells isolated from the
      mice exhibited Klk1 expression at detectable levels when cultured in the presence
      of estradiol-17beta. mK1 was characterized using the recombinant active enzyme.
      mK1 had trypsin-like activity with a strong preference for Arg over Lys in the P1
      position, and its activity was inhibited by typical serine protease inhibitors.
      Casein, gelatin, fibronectin, collagen type IV, and high-molecular-weight
      kininogen were degraded by mK1. The single-chain tissue-type plasminogen
      activator was converted to the two-chain form by mK1. In addition, mK1 degraded
      insulin-like growth factor binding protein-3. The present data suggest that mK1
      may be implicated in the growth of uterine endometrial tissues during the
      proliferative phase.

PMID- 17219432
TI  - Expression of estrogen receptors alpha and beta in the corpus luteum and uterus
      from non-pregnant and pregnant llamas.
AB  - Because estrogen may be involved in maternal recognition of pregnancy and
      embryonic migration in llamas, expression of estrogen receptor subtypes alpha
      (ERalpha) and beta (ERbeta) was evaluated in corpus luteum (CL), endometrium, and
      uterus using relative RT-PCR. Tissues were recovered from sterile-mated (SM) and
      pregnant (PG) females during Days 7-11 and 7-13 (Day 0 = day of mating),
      respectively, and follicular phase and juvenile females. Luteal expression of
      ERalpha and beta was similar (P > 0.10) in SM and PG females and within Days 7
      11, however, expression of ERalpha in ovarian tissue from follicular phase
      females was greater (P < 0.05) than Days 7 and 9 CL. Uterus expressed less
      ERalpha and beta compared to endometrium (P = 0.07 and P < 0.01, respectively).
      Expression of ERalpha was greater (P < 0.05) in Day 7 and follicular phase uteri
      than Days 9 and 11, Day 13 PG and juvenile uteri. Uterine ERbeta expression was
      greater (P = 0.09) in PG versus SM females and in mated compared to follicular
      phase females (P < 0.05). Endometrial expression of ERalpha and beta did not
      differ (P > 0.10) between SM and PG females or by day. The presence of luteal ER
      during this period may mean a role for estradiol in maternal recognition of
      pregnancy. Observed increases in uterine ER expression with no changes in
      endometrium suggest expression increased in myometrium and/or perimetrium.
      Upregulation of myometrial ERbeta in PG females may be involved in supporting
      uterine migration of the embryo.

PMID- 17219433
TI  - A gene trap mutation of a murine homolog of the Drosophila stem cell factor
      Pumilio results in smaller testes but does not affect litter size or fertility.
AB  - Members of the Pumilio (also called PUF) gene family belong to a class of highly
      conserved developmental regulators that are present in both flies and humans.
      Much is known about the function of Pumilio genes in invertebrate development, in
      particular their role as stem cell factors required for maintenance and/or self
      renewal of germline stem cells in Drosophila and Caenorhabditis elegans. It
      remains unknown whether Pumilio genes are also required for development in
      mammals; however, several lines of evidence suggest similar functions based on
      extensive sequence homology, similar RNA-binding properties to their invertebrate
      counterparts and well-documented interactions with germ cell factors required for
      fertility. Here we report characterization of a gene trap mutation that disrupts
      the mouse Pumilio-2 (Pum2) gene. Our data confirm that Pumilio-2 is expressed
      most abundantly in germ cells with the highest expression in undifferentiated
      gonocytes and spermatogonia. Furthermore, the mutation in Pum2 results in
      significantly smaller testes although the mutants are otherwise viable and
      fertile. In addition, we observed no stronger reproductive defects on a genetic
      background homozygous for a Pum2 null mutation and heterozygous for a Dazl
      mutation than Pum2 mutant alone. Thus, as in C. elegans where single members of
      the Pumilio gene family are dispensable for reproductive development and
      viability, this individual member of the Pumilio gene family in mice is also not
      essential for reproduction or viability.

PMID- 17219434
TI  - PP2Cdelta (Ppm1d, WIP1), an endogenous inhibitor of p38 MAPK, is regulated along
      with Trp53 and Cdkn2a following p38 MAPK inhibition during mouse preimplantation
      development.
AB  - Preimplantation embryos utilize mitogen-activated protein kinase signaling (MAPK)
      pathways to relay signals from the external environment to prepare appropriate
      responses and adaptations to a changing milieu. It is therefore important to
      investigate how MAPK pathways are regulated during preimplantation development.
      This study was conducted to investigate whether PP2Cdelta (Ppm1d, WIP1) is
      expressed during mouse preimplantation development and to determine the
      influences of p38 MAPK inhibition on expression of Trp53 (p53), Ppm1d, (WIP1),
      and Cdkn2a (p16) during mouse preimplantation development. Our results indicate
      that Trp53, Ppm1d, and Cdkn2a mRNAs and TRP53 and PP2Cdelta proteins are
      expressed throughout mouse preimplantation development. Treatment of 2-cell
      embryos with SB220025 (potent inhibitor of p38 MAPK alpha/beta/MAPK 14/11)
      significantly increased Trp53, Ppm1d and Cdkn2a and Mapk14 mRNA levels at 12 and
      24 hr. Treatment of 8-cell embryos with SB220025 for 12 hr increased Trp53,
      Ppm1d, and Cdkn2a mRNA levels, but not Mapk14 mRNA levels. Treatment of 8-cell
      embryos for 24 hr increased Trp53, and Ppm1d mRNA levels, but decreased Cdkn2a
      and Mapk14 mRNA levels. Therefore, blockade of p38 MAPK activity is associated
      with embryo stage specific influences on Trp53, Ppm1d, Cdkn2a, and Mapk14
      expression during mouse preimplantation development. These results define
      downstream targets of p38 MAPK during preimplantation development and indicate
      that the p38 MAPK pathway regulates Trp53, Ppm1d, and Cdkn2a expression. This
      study increases our understanding of the mechanisms controlling preimplantation
      development and of the interactions between preimplantation embryos and their
      culture environments.

PMID- 17219435
TI  - Morphologic and histologic comparisons between in vivo and nuclear transfer
      derived porcine embryos.
AB  - Nuclear transfer (NT) is an inefficient but invaluable tool of the biotechnology
      industry. This study looked at abnormalities associated with peri-implantation NT
      porcine embryos. Four experimental groups were examined: nonpregnant animals, in
      vivo pregnant animals, NT recipients, and manipulation control embryos (MC).
      Embryos (Day 10, 12, or 14) were evaluated for embryonic disc diameter, gross
      morphology, nucleoli density, and mitotic figure index. Day 12 (P < or = 0.03)
      and Day 14 (P < or = 0.01) NT embryos had increased numbers of nucleoli, and Day
      14 NT embryos had an increased (P < or = 0.03) mitotic index compared to in vivo
      and MC embryos. In vivo produced Day 14 embryos had increased (P < or = 0.01)
      disk diameters when compared to other embryos except for MC Day 14, which also
      showed increases (P < or = 0.01) in disk diameter except when compared to in vivo
      produced Day 12 and Day 14 embryos. In vivo produced Day 12 had greater (P < or =
      0.03) disk diameters when compared to NT and MC embryos except for MC Day 14, and
      in vivo produced Day 14 embryos, which had a significantly increased (P < or =
      0.01) disk diameter. In vivo produced Day 14 embryos were morphologically more
      advanced (P < or = 0.01) than Day 14 NT and MC counterparts. NT embryos develop
      at a slower rate than their in vivo produced counterparts. The increase in
      nucleoli and mitotic index of NT embryos suggest the cell cycle may be affected
      or the NT embryos are employing other means to compensate for slow development.
      The techniques used during NT also appear to compromise embryo development.

PMID- 17219436
TI  - MMP-7 (matrilysin) expression in human brain tumors.
AB  - Matrix metalloproteinases (MMP) which degrades protein components of the extra
      cellular matrix and basement membrane seems to be largely involved in cancer
      invasiveness. MMP proteolitic activity essentially comes from stromal cells but
      matrilysin (MMP-7) is produced by the tumor itself. Thus, MMP-7 is investigated
      to address the particular invasive behavior of human glioma. Both MMP-7 mRNA and
      protein were clearly identified in human glioma. MMP-7 mRNA expression was highly
      variable within our glioma population. When analyzing MMP-7 mRNA expression in
      different primary brain tumors, we found highly variable levels of expression not
      related to their invasive behavior. In successive biopsies obtained in the same
      patients with glioblastoma, MMP-7 mRNA was quantified and appeared variable, but
      intra-individual variations were lower than inter-individual differences. With a
      xenograft model of U87 human tumors in RAG2/gamma(c) immune-deficient mice, the
      strict tumor origin of MMP-7 was shown. Additionally, MMP-7 expression by U87
      cells which is low in culture was stimulated by these cells while forming tumors
      and the level of expression was higher when the tumor cells were implanted within
      the brain. These data provide some consistent information about cross-talk
      occurring between the tumor and the surrounding stroma to regulate MMP-7
      expression.

PMID- 17219437
TI  - Carbonic anhydrase-related protein VIII promotes colon cancer cell growth.
AB  - Increased expression of carbonic anhydrase-related protein (CA-RP) VIII has
      previously been shown in colorectal carcinoma. Since CA-RP has no catalytic
      carbonic anhydrase (CA) activity, the present study attempted to elucidate its
      biological significance in colon cancer cells. From a colon cancer cell line
      (LoVo), we established clones that overexpressed CA-RP VIII (LoVo-CA8) and a
      control transfectant with a vector alone (LoVo-pCIneo) and studied alterations in
      the biological behaviors of the tumor cells both in vitro and in vivo. LoVo-CA8
      cells showed significantly increased mRNA and protein expressions of CA-RP VIII
      as compared to LoVo-pCIneo cells. Cell proliferation, colony formation, and cell
      invasion assays showed that LoVo-CA8 cells had significantly higher cell
      proliferative and invasive abilities as compared to parental LoVo and LoVo-pCIneo
      cells in vitro. In an in vivo xenograft assay, LoVo-CA8 cells showed a higher
      tumor growth rate than parental LoVo cells. Further, small interfering RNA
      (siRNA)-mediated knockdown of CA-RP VIII revealed significant inhibition in cell
      proliferation and colony formation of a colon cancer cell line HCT116, which
      showed high endogenous expression of CA-RP VIII. These findings indicated that CA
      RP VIII plays a role in the growth of colon cancer cells.

PMID- 17219438
TI  - Structure-activity relationship of flavonoids for inhibition of epidermal growth
      factor-induced transformation of JB6 Cl 41 cells.
AB  - We found that quercetin, myricetin, quercetagetin, fisetin, (-)-epigallocatechin
      gallate (EGCG), and theaflavins, among 24 flavonoids examined, markedly inhibited
      epidermal growth factor (EGF)-induced cell transformation of mouse epidermal JB6
      Cl 41 cells. The six flavonoids suppressed the EGF-induced activation of
      activator protein 1 (AP-1). In addition, myricetin, quercetagetin, EGCG, and
      theaflavins directly inhibited EGF-induced phosphatidylinositol 3-kinase (PI3K)
      activation. The important structural features of flavonoids for cell
      transformation-inhibitory activity are 3'- and 4'-OH on the B-ring, 3-OH on the C
      ring, C2=C3 double bond in the C-ring, and the phenylchromone (C6-C5-C6) skeleton
      in the flavonols, and the galloyl group in EGCG and theaflavins. Our results
      provide new insight into possible mechanisms of the anti-carcinogenic effects of
      flavonoids, and could help to provide a basis for the design of novel cancer
      chemopreventive agents.

PMID- 17219439
TI  - A novel low-molecular weight inhibitor of focal adhesion kinase, TAE226, inhibits
      glioma growth.
AB  - Glioblastomas are highly lethal cancers that resist current therapies. Novel
      therapies under development target molecular mechanisms that promote glioblastoma
      growth. In glioblastoma patient specimens, the non-receptor tyrosine kinase focal
      adhesion kinase (FAK) is overexpressed. Upon growth factor receptor stimulation
      or integrin engagement, FAK is activated by phosphorylation on critical tyrosine
      residues. Activated FAK initiates a signal transduction cascade which promotes
      glioma growth and invasion by increasing cellular adhesion, migration, invasion,
      and proliferation. We find that human glioma cell lines express different levels
      of total FAK protein and activating phosphorylation of tyrosine residues Tyr397,
      Tyr861, and Tyr925. As all glioma cell lines examined expressed phosphorylated
      FAK, we examined the efficacy of a novel low-molecular weight inhibitor of FAK,
      TAE226, against human glioma cell lines. TAE226 inhibited the phosphorylation of
      FAK as well as the downstream effectors AKT, extracellular signal-related kinase,
      and S6 ribosomal protein in multiple glioma cell lines. TAE226 induced a
      concentration-dependent decrease in cellular proliferation with an associated
      G(2) cell cycle arrest in every cell line and an increase in apoptosis in a cell
      line-specific manner. TAE226 also decreased glioma cell adhesion, migration, and
      invasion through an artificial extracellular matrix. Together, these data
      demonstrate the potential benefit of TAE226 for glioma therapy.

PMID- 17219440
TI  - Association of the EGFR intron 1 CA repeat length with lung cancer risk.
AB  - Epidermal growth factor receptor (EGFR) plays an important role in the
      development and progression of lung cancer. A previous report noted that an
      increased number of polymorphic CA repeats in the first intron of the EGFR gene
      results in decreased transcriptional activity. To estimate the association of the
      length of polymorphic CA repeats in intron 1 of the EGFR gene with lung cancer, a
      case-control study of 176 lung cancer patients and 161 controls was conducted in
      Caucasians. This case-control study is based on two existing prospective cohorts:
      the Early Detection Research Network (EDRN) and the Lung Cancer Specialized
      Program of Research Excellence (SPORE) at the University of Pittsburgh. The
      frequencies of the SL (one allele>16 repeats), and SS (both allele<or=16 repeats)
      genotypes were statistically higher among the cases than in the controls (OR:
      1.94 and 3.04, 95% CI: 1.16-3.23 and 1.53-6.04, P-value: 0.01 and 0.001,
      respectively). When the length of EGFR-CA repeat was analyzed by the sum of the
      number of repeats in two alleles, the frequency of the shorter repeats
      (sum<or=36) was 79.6% versus 63.4%, respectively, and the frequency of the longer
      repeats (sum>36) was 20.5% versus 36.7%, for lung cancer cases versus controls.
      The lower sum of EGFR-CA repeats associated with the risk of lung cancer; the
      estimated odds ratio was 2.25 with 95% confidence interval: 1.38-3.66 (P=0.001).
      Associations involving EGFR-CA repeat genotype and EGFR-CA repeat sum remained
      significant when adjusted for age, gender, and tobacco exposure. Our study, which
      is preliminary, demonstrates for the first time that shorter EGFR-CA repeats
      associate with lung cancer risk. The number of EGFR-CA repeats identifies a
      possible susceptible population to lung cancer.

PMID- 17219441
TI  - Secondary cytoreductive surgery for localized, recurrent epithelial ovarian
      cancer: analysis of prognostic factors and survival outcome.
AB  - BACKGROUND: The objective of this study was to evaluate the role of secondary
      cytoreductive surgery in the outcome of patients who had recurrent epithelial
      ovarian carcinoma that was limited to <or=5 recurrence sites within the abdomen
      or pelvis on preoperative imaging studies and attempt to define selection
      criteria associated with improved survival, with specific attention to the number
      of lesions suspicious for recurrent disease. METHODS: : Patients who underwent
      secondary surgical cytoreduction for recurrent epithelial ovarian cancer between
      September 1997 and March 2005 were identified retrospectively from tumor registry
      databases. Study inclusion criteria required a complete clinical response to
      primary therapy, >or=12 months between initial diagnosis and recurrence, and
      <or=5 recurrence sites on preoperative imaging studies. Univariate and
      multivariate logistic regression analyses were used to evaluate the effect of
      clinicopathologic variables on overall postrecurrence survival. RESULTS: Fifty
      five patients met the study inclusion criteria. The median patient age at
      recurrence was 57.7 years, and the median diagnosis-to-recurrence interval was 32
      months (range, 12-164 months). Complete cytoreduction was achieved in 41 patients
      (74.5%). On multivariate analysis, the statistically significant and independent
      predictors of overall survival were a diagnosis-to-recurrence interval >or=18
      months (median survival, 49 months vs 3 months; P < .01), the number of
      radiographic recurrence sites (median survival, 50 months for patients with 1 or
      2 sites vs 12 months for patients with 3 to 5 sites; P < .03), and residual
      disease (median survival, 50 months for patients with no macroscopic residual
      disease vs 7.2 months for patients with macroscopic residual disease; P < .01).
      Age, tumor grade, histology, CA-125 level, ascites, and tumor size were not
      associated significantly with survival. CONCLUSIONS: : The current data supported
      the definition of localized recurrent ovarian cancer as patients with 1 or 2
      radiographic recurrence sites. In this select population, a diagnosis-to
      recurrence interval >or=18 months and complete secondary surgical cytoreduction,
      which was achievable in the majority of patients, were associated with a median
      postrecurrence survival of approximately 50 months.

PMID- 17219443
TI  - A pilot study of the vulnerable elders survey-13 compared with the comprehensive
      geriatric assessment for identifying disability in older patients with prostate
      cancer who receive androgen ablation.
AB  - BACKGROUND: Impairments in geriatric domains adversely affect health outcomes of
      the elderly. The Comprehensive Geriatric Assessment (CGA) is a key component of
      the treatment approach for older cancer patients, but it is time consuming. In
      this pilot study, the authors evaluated the validity of a brief, functionally
      based screening tool, the Vulnerable Elders Survey-13 (VES-13), for identifying
      older patients with prostate cancer (PCa) with impairment in the oncology clinic
      setting. METHODS: Patients with PCa aged >or=70 years who actively were receiving
      androgen ablation treatment and who were followed within the clinics at the
      University of Chicago were eligible. Patients self-completed the VES-13 and CGA
      instruments and repeated the VES-13 1 month later. Physical performance and
      cognitive assessments were administered by a research assistant. RESULTS: Of 50
      participating patients, 50% were identified as impaired by the VES-13 (score
      >or=3). Sixty percent of patients scored as impaired on >or=2 tests within the
      CGA, exhibiting deficits in multiple domains. The reliability of the VES-13
      (Pearson correlation coefficient) was 0.92. The cut-off score of 3 on the VES-13
      had 72.7% sensitivity and 85.7% specificity for CGA deficits and was highly
      predictive for identifying impairment (area under the receiver operating
      characteristic curve, 0.90). Patients who had mean VES-13 scores >or=3 performed
      significantly worse on evaluations of activities of daily living (P = .001),
      physical performance (P = .002), comorbidity (P = .004), and cognitive impairment
      (P = .003). CONCLUSIONS: Functional and cognitive impairments are highly
      prevalent among older patients with PCa who receive androgen ablation in oncology
      clinics. The current results indicated that the brief VES-13 performed nearly as
      well as a conventional CGA in detecting geriatric impairment in this population.

PMID- 17219444
TI  - Activity of decitabine, a hypomethylating agent, in chronic myelomonocytic
      leukemia.
AB  - BACKGROUND: Hypomethylating agents have activity in myelodysplastic syndrome
      (MDS) and have received approval for the treatment of both MDS and chronic
      myelomonocytic leukemia (CMML). The specific efficacy in CMML has not been
      detailed in a large number of patients. The aim of the study was to evaluate the
      activity and safety of decitabine in CMML. METHODS: Nineteen adults with a
      diagnosis of CMML treated on decitabine studies were analyzed. Decitabine was
      given at 100 mg/m(2) per course every 4 weeks. The median number of courses given
      was 9 (range, 1-18). RESULTS: Overall, 11 patients (58%) achieved complete
      response (CR) and 2 (11%) had hematologic improvement (HI), for an overall
      response rate of 69% according to the modified International Working Group (IWG)
      criteria. Median survival was 19 months. Severe (grade 3-4) extramedullary side
      effects were rare. CONCLUSIONS: Decitabine is active in CMML. Studies of
      combinations of decitabine with topoisomerase I inhibitors or other active anti
      CMML agents are indicated.

PMID- 17219445
TI  - Adjuvant and neoadjuvant chemotherapy for Ewing sarcoma family tumors in patients
      aged between 40 and 60: report of 35 cases and comparison of results with 586
      younger patients treated with the same protocols in the same years.
AB  - BACKGROUND: The clinical and pathologic features of 46 patients 40 to 60 years
      old with Ewing sarcoma family tumor (ESFT) diagnosed at the authors' institute
      between 1972 and 2000 were reviewed. METHODS: Ten patients with metastatic tumors
      at presentation went elsewhere for treatment; 35 of 36 remaining cases with
      localized disease were treated at the authors' institution according to different
      chemotherapy protocols activated in successive years. In patients with
      nonmetastatic tumors local treatment was surgery in 9 patients, radiotherapy in
      16, and surgery followed by radiotherapy in 10. RESULTS: At follow-up times
      ranging from 6 and 34 years (mean, 17.8 years), 15 patients (42.9%) remained
      continuously disease-free, 19 experienced recurrence, and 1 died of chemotherapy
      related toxicity. The 5- and 10-year event-free survivals were 42.9% and 35.2%,
      respectively, and the 5- and 10-year overall survivals were 46.1% and 42.8%,
      respectively. Comparing this group of patients with 586 cases of younger patients
      seen in the same period at Rizzoli, the only difference between the 2 groups was
      a significantly higher rate of tumors located in the soft tissues with a larger
      volume in the older group. The results achieved were comparable in the 2 groups,
      although the older group had a lower chemotherapy dose-intensity and a higher
      rate of WHO grade 4 hematologic toxicity. CONCLUSIONS: For patients with
      localized disease treated with adjuvant and neoadjuvant chemotherapy the results
      were essentially comparable in the 2 groups. It is concluded that patients 40
      years or older with ESFT should be treated in the same way as younger patients
      and included in treatment trials for these tumors.

PMID- 17219446
TI  - Effect of obesity on survival in epithelial ovarian cancer.

PMID- 17219448
TI  - Human papillomavirus testing and molecular markers of cervical dysplasia and
      carcinoma.
AB  - Cervical cancer is the second most common cancer in women worldwide. Human
      papillomavirus (HPV) is the etiologic agent for the vast majority of premalignant
      and malignant lesions, and high-risk HPV types can be detected in almost all
      cases of cervical dysplasia and carcinoma. HPV testing has been widely adopted
      for the triage of patients after a cervical cytology screening test (Papanicolaou
      smear or liquid-based cervical cytology such as ThinPrep or SurePath)
      interpretation of atypical squamous cells of undetermined significance (ASCUS),
      and HPV testing is increasingly used for screening in conjunction with cervical
      cytology. Although cervical cytology is a highly effective screening test for
      cancer, it has limited specificity for clinically significant lesions in cases
      with low-grade cytologic abnormalities. Up to a quarter of all patients may have
      a false-negative result on the basis of cervical cytology testing alone. This
      review focuses on HPV testing methods and molecular markers and their clinical
      relevance. HPV testing and surrogate molecular markers of HPV infection
      (p16INK4a) may help identify cases that are associated with underlying high-grade
      premalignant or malignant lesions and may also reduce aggressive treatment of
      patients with low-grade lesions.

PMID- 17219447
TI  - Inactivation of human mutL homolog 1 and mutS homolog 2 genes in head and neck
      squamous cell carcinoma tumors and leukoplakia samples by promoter
      hypermethylation and its relation with microsatellite instability phenotype.
AB  - BACKGROUND: A subset of head and neck squamous cell carcinoma (HNSCC) exhibits a
      microsatellite instability (MIN) phenotype. The authors correlated alterations in
      the mismatch-repair genes human mutL homolog 1 (hMLH1) and human mutS homolog 2
      (hMSH2) in primary head and neck squamous cell carcinoma (HNSCC) tumors and in
      samples of leukoplakia with the MIN phenotype. METHODS: One hundred twenty-three
      paired HNSCC normal and tumor tissues and 27 leukoplakia samples were examined
      for hypermethylation of hMLH1 and hMSH2 promoters. The hypermethylation status of
      the tissues was confirmed by expression studies. Sixty-three of 123 randomly
      selected tumors and all 27 leukplakia samples were genotyped with 8
      microsatellite markers to determine MIN. RESULTS: Fifty percent of HNSCC tumors
      and 63% of leukoplakia samples harbored hypermethylation at either or both hMLH1
      and hMSH2 promoters. Normal tissues adjacent to methylation-positive tumors also
      demonstrated hypermethylation of both promoters at a high frequency (25%). A
      positive correlation between tobacco habit and promoter hypermethylation was
      observed (P = .001). A correlation was observed between MIN and the frequency of
      promoter hypermethylation in the leukoplakia samples, but no such trend was
      observed in the HNSCC tumors. It is noteworthy that patients who had a high
      frequency of MIN-positive tumors exhibited hypermethylation in both the affected
      tissues and the adjacent normal tissues (P = .007). Patients with a tobacco habit
      who had promoter hypermethylation at both the affected tissues and the adjacent
      normal tissues had tumors that mostly were MIN positive (P = .047). CONCLUSIONS:
      The current results suggested that tobacco-addicted individuals are more
      susceptible to promoter hypermethylation of hMLH1 and hMSH2 and that, if such
      hypermethylation occurs in the normal squamous epithelium of the head and neck
      region, then those tissues are likely to develop into tumors that involve the MIN
      pathway.

PMID- 17219450
TI  - Oxidative cleavage of 3-alkoxy-2,5-dihydrofurans and its application to the de
      novo synthesis of rare monosaccharides as exemplified by L-cymarose.

PMID- 17219449
TI  - Nasal inoculation of an adenovirus vector encoding 11 tandem repeats of Abeta1-6
      upregulates IL-10 expression and reduces amyloid load in a Mo/Hu APPswe PS1dE9
      mouse model of Alzheimer's disease.
AB  - BACKGROUND: One of the pathological hallmarks of Alzheimer's disease (AD) is
      deposits of amyloid beta-peptide (Abeta) in neuritic plaques and cerebral
      vessels. Immunization of AD mouse models with Abeta reduces Abeta deposits and
      improves memory and learning deficits. Because recent clinical trials of
      immunization with Abeta were halted due to brain inflammation that was presumably
      induced by a T-cell-mediated autoimmune response, vaccination modalities that
      elicit predominantly humoral immune responses are currently being developed.
      METHODS: We have nasally immunized a young AD mouse model with an adenovirus
      vector encoding 11 tandem repeats of Abeta1-6 fused to the receptor-binding
      domain (Ia) of Pseudomonas exotoxin A (PEDI), AdPEDI-(Abeta1-6)(11), in order to
      evaluate the efficacy of the vector in preventing Abeta deposits in the brain. We
      also have investigated immune responses of mice to AdPEDI-(Abeta1-6)(11).
      RESULTS: Nasal immunization of an AD mouse model with AdPEDI-(Abeta1-6)(11)
      elicited a predominant IgG1 response and reduced Abeta load in the brain. The
      plasma IL-10 level in the AD mouse model was upregulated after immunization and,
      upon the stimulation with PEDI-(Abeta1-6)(11), marked IL-10 responses were found
      in splenic CD4(+) T cells from C57BL/6 mice that had been immunized with AdPEDI
      (Abeta1-6)(11). CONCLUSIONS: These results suggest that the induction of Th2
      biased responses with AdPEDI-(Abeta1-6)(11) in mice is mediated in part through
      the upregulation of IL-10, which inhibits activation of dendritic cells that
      dictate the induction of Th1 cells.

PMID- 17219451
TI  - Assessment of chelatable mitochondrial iron by using mitochondrion-selective
      fluorescent iron indicators with different iron-binding affinities.
AB  - Chelatable cellular iron, and chelatable mitochondrial iron in particular, has
      yet to be well characterized, so the overall strength with which these "loosely
      bound" iron ions (presumably mainly Fe(II)) are
      intracellularly/intramitochondrially bound is unclear. We have previously
      reported the first selective mitochondrial iron indicator: rhodamine B 4-[(1,10
      phenanthrolin-5-yl)aminocarbonyl]benzyl ester (RPA). With this compound as a
      model, we have now developed two additional mitochondrial iron indicators with
      very different iron-binding affinities and have applied these to the study of the
      chelatable iron pool in the mitochondria of isolated rat liver cells. With the
      new indicator rhodamine B 4-[(2,2'-bipyridin-4-yl)aminocarbonyl]benzyl ester
      (RDA), with 2,2'-bipyridine as chelating unit (log beta(3)=17.5), essentially the
      same iron concentration (16.0+/-1.9 microM) was determined as with RPA (log
      beta(3)=21.1), despite the four orders of magnitude difference in Fe(II)-binding
      affinity. This not only demonstrates the reliability of the procedure, but also
      confirms that iron complexation by these indicators does not induce any
      significant release of iron from the iron-storage proteins on the timescale of
      the experiment. In contrast, the indicator rhodamine B 4-[bis(pyridin-2
      ylmethyl)aminomethyl]benzyl ester (PIRO), with an N,N-bis(pyridin-2
      ylmethyl)amine group as chelating component (log beta(2)=12.2), could not compete
      against the array of endogenous ligands. The intramitochondrial concentrations of
      the three indicators were determined to be in the range of 100 microM: that is,
      about three orders of magnitude lower than the total concentration of endogenous
      compounds that might chelate iron ions. It is therefore estimated that chelatable
      mitochondrial iron ions are bound by endogenous ligands with apparent stability
      constants (log K(app)) of between 9 and 14.

PMID- 17219452
TI  - Highly efficient chemoenzymatic synthesis of novel branched thiooligosaccharides
      by substrate direction with glucansucrases.

PMID- 17219453
TI  - A new mechanism for ethanol oxidation mediated by cytochrome P450 2E1: bulk
      polarity of the active site makes a difference.

PMID- 17219454
TI  - Hydrogen-atom transfer in open-shell organometallic chemistry: the reactivity of
      Rh(II)(cod) and Ir(II)(cod) radicals.
AB  - A series of new metalloradical rhodium and iridium complexes [M(II)(cod)(N
      ligand)](2+) in the uncommon oxidation state +II were synthesized by one-electron
      oxidation of their [M(I)(cod)(N-ligand)](+) precursors (M=Rh, Ir; cod=(Z,Z)-1,5
      cyclooctadiene; and N-ligand is a podal bis(pyridyl)amine ligand: N,N-bis(2
      pyridylmethyl)amine (dpa), N-(2-pyridylmethyl)-N-(6-methyl-2-pyridylmethyl)amine
      (pla), or N-benzyl-N,N-bis(6-methyl-2-pyridylmethyl)amine (Bn-dla). EPR
      spectroscopy, X-ray diffraction, and DFT calculations reveal that each of these
      [M(II)(cod)(N-ligand)](2+) species adopts a square-pyramidal geometry with the
      two cod double bonds and the two pyridine fragments in the basal plane and the
      N(amine) donor at the apical position. The unpaired electron of these species
      mainly resides at the metal center, but the apical N(amine) donor also carries a
      considerable fraction of the total spin density (15-18 %). Density functional
      calculations proved a valuable tool for the analysis and simulation of the
      experimental EPR spectra. Whereas the M(II)(olefin) complexes are quite stable as
      solids, in solution they spontaneously transform into a 1:1 mixture of
      M(III)(allyl) species and protonated M(I)(olefin) complexes (in the forms
      [M(I)(olefin)(protonated N-ligand)](2+) for M=Rh and [M(III)(H)(olefin)(N
      ligand)](2+) for M=Ir). Similar reactions were observed for the related propene
      complex [M(II)(propene)(Me(2)tpa)](2+) (Me(2)tpa=N,N,N-tris(6-methyl-2
      pyridylmethyl)amine). The decomposition rate of the [M(II)(cod)(N-ligand)](2+)
      species decreases with increasing N-ligand bulk in the following order:
      dpa>pla>Bn-dla. Decomposition of the most hindered [M(II)(cod)(Bn-dla)](2+)
      complexes proceeds by a second-order process. The kinetic rate expression
      v=k(obs)[M(II)](2) in acetone with k(obs)=k'[H(+)][S], where [S] is the
      concentration of additional coordinating reagents (MeCN), is in agreement with
      ligand-assisted dissociation of one of the pyridine donors. Solvent coordination
      results in formation of more open, reactive species. Protonation of the
      noncoordinating pyridyl group increases the concentration of this species, and
      thus [H(+)] appears in the kinetic rate expression. The kinetic data are in
      agreement with bimolecular hydrogen-atom transfer from M(II)(cod) to another
      M(II) species (DeltaH( not equal)=11.5+/-2 kcal mol(-1), DeltaS( not equal)=-27+/
      10 cal K(-1) mol(-1), and DeltaG( not equal)(298 K)=19.5+/-5 kcal mol(-1)).

PMID- 17219455
TI  - The complete structure and pro-inflammatory activity of the lipooligosaccharide
      of the highly epidemic and virulent gram-negative bacterium Burkholderia
      cenocepacia ET-12 (strain J2315).
AB  - Members of genus Burkholderia include opportunistic Gram-negative bacteria that
      are responsible for serious infections in immunocompromised and cystic fibrosis
      (CF) patients. The Burkholderia cepacia complex is a group of microorganisms
      composed of at least nine closely related genomovars. Among these, B. cenocepacia
      is widely recognized to cause epidemics associated with excessive mortality.
      Species that belong to this strain are problematic CF pathogens because of their
      high resistance to antibiotics, which makes respiratory infections difficult to
      treat and impossible to eradicate. Infection by these bacteria is associated with
      higher mortality in CF and poor outcomes following lung transplantation. One
      virulence factor contributing to this is the pro-inflammatory lipopolysaccharide
      (LPS) molecules. Thus, the knowledge of the lipopolysaccharide structure is an
      essential prerequisite to the understanding of the molecular mechanisms involved
      in the inflammatory process. Such data are instrumental in aiding the design of
      antimicrobial compounds and for developing therapeutic strategies against the
      inflammatory cascade. In particular, defining the structure of the LPS from B.
      cenocepacia ET-12 clone LMG 16656 (also known as J2315) is extremely important
      given the recent completion of the sequencing project at the Sanger Centre using
      this specific strain. In this paper we address this issue by defining the pro
      inflammatory activity of the pure lipopolysaccharide, and by describing its full
      primary structure. The activity of the lipopolysaccharide was tested as a
      stimulant in human myelomonocytic U937 cells. The structural analysis was carried
      out by compositional analysis, mass spectrometry and 2D NMR spectroscopy on the
      intact lipooligosacchride (LOS) and its fragments, which were obtained by
      selective chemical degradations.

PMID- 17219456
TI  - New branched DNA constructs.
AB  - The Watson-Crick base pairing of DNA is an advantageous phenomenon that can be
      exploited when using DNA as a scaffold for directed self-organization of
      nanometer-sized objects. Several reports have appeared in the literature that
      describe the generation of branched DNA (bDNA) with variable numbers of arms that
      self-assembles into predesigned architectures. These bDNA units are generated by
      using cleverly designed rigid crossover DNA molecules. Alternatively, bDNA can be
      generated by using synthetic branch points derived from either nucleoside or non
      nucleoside building blocks. Branched DNA has scarcely been explored for use in
      nanotechnology or from self-assembling perspectives. Herein, we wish to report
      our results for the synthesis, characterization, and assembling properties of
      asymmetrical bDNA molecules that are able to generate linear and circular bDNA
      constructs. Our strategy for the generation of bDNA is based on a branching point
      that makes use of a novel protecting-group strategy. The bDNA units were
      generated by means of automated DNA synthesis methods and were used to generate
      novel objects by employing chemical and biological techniques. The entities
      generated might be useful building blocks for DNA-based nanobiotechnology.

PMID- 17219457
TI  - Inherently chiral molecular clips: synthesis, chiroptical properties, and
      application to chiral discrimination.
AB  - Inherently chiral molecular clips (MCs), pseudoenantiomeric anti-1 and anti-2, as
      well as mesoid syn-3, were synthesized by diastereodifferentiating repetitive
      Diels-Alder reactions of the achiral bisdienophile 6 with chiral diene 5
      generated in situ from (-)-menthyl 3,4-bis(dibromomethyl)benzoate 4. These MCs
      were successfully separated by chiral HPLC to give optically active anti-1 and
      anti-2 and almost optically inactive syn-3. The structures of anti-1, anti-2, and
      syn-3 were assigned by high-resolution NMR and the absolute configurations of
      anti-1 and anti-2 were determined by the exciton-chirality method. Optically
      active anti-2 can serve as a chiral host. It binds the HCl adduct of D-tryptophan
      methyl ester (D-TrpOMeHCl) 3.5 times stronger than the L-enantiomer (KD/KL=3.5).

PMID- 17219459
TI  - Study and improvement of the conditions for production of a novel alkali stable
      catalase.
AB  - Catalase (CAT) is an enzyme capable of catalyzing the conversion of H(2)O(2) to
      O(2) and H(2)O. It has recently acquired interest due to its attractive potential
      application in the textile industries. In a previous study, a bacterium with
      slight halophilic and alkaliphilic characteristics, Bacillus sp. F26, was
      isolated and found to produce high-level alkaline CAT. In the present study, the
      effects of culture conditions on the CAT production were investigated. The
      results showed that the highest activity of CAT (13.9 U/mg protein) was obtained
      when glucose (15 g/L) was used as carbon source. The utilization of the mixture
      of corn steep liquid and beef extract stimulated both bacterial growth and CAT
      synthesis. The highest biomass (4.5 g/L) and activity of CAT (16.5 U/mg protein)
      were found synchronously when 10 g/L corn steep liquid and 10 g/L beef extract
      were used as nitrogen source. The addition of H(2)O(2) as an oxidative stress was
      used to enhance CAT production in the flasks. It was found that the activity of
      CAT was increased by 51.3-22.8 U/mg protein compared with the control when 2
      mmol/L H(2)O(2) was added at later exponential phases (16 h), although the cell
      growth was significantly inhibited. Based on the above, an exponential H(2)O(2)
      feed strategy was developed, in which the feed rate of H(2)O(2) was controlled
      according to specific cell growth rate (mu). In this way, the maximum CAT
      production (29.9 U/mL) was obtained, which was 92.8 and 20.7% higher than that in
      batch and constant rate fed-batch fermentation, respectively.

PMID- 17219458
TI  - Analysis of the products from enzymatic scouring of cotton.
AB  - This article discusses the analysis of the hydrolysis products from one-step
      scouring of cotton using pectinase and two-step scouring of cotton using lipase
      then cellulase, protease then cellulase, or lipase/protease then cellulase, to
      improve water absorbency of cotton. UV spectrophotometric analysis indicated that
      the pectinase scouring process produced approximately 18-fold higher amounts of
      reducing sugars and galacturonic acid than any of the two-step scouring
      processes. The production rate of reducing sugars and galacturonic acid from most
      of the scouring processes showed a decrease with an increase in time. HPLC
      analysis revealed that the lipase/protease/cellulase scouring processes produced
      approximately 5-fold higher amounts of 17 amino acids than the pectinase scouring
      process. GC analysis for 18 fatty acids (C(8)-C(24)) revealed that three major
      fatty acids, palmitic acid, stearic acid, and behenic acid, were found on both
      the scoured and the unscoured fabrics. Scoured fabrics were tested for content of
      proteins, extractable components, waxes, and anionic components including
      pectins, and some differences among the fabric scoured with different enzyme
      combinations were found.

PMID- 17219460
TI  - Wax removal for accelerated cotton scouring with alkaline pectinase.
AB  - A rational approach has been applied to design a new environmentally acceptable
      and industrially viable enzymatic scouring process. Owing to the substrate
      specificity, the selection of enzymes depends on the structure and composition of
      the substrate, i.e. cotton fibre. The structure and composition of the outer
      layers of cotton fibre has been established on the basis of thorough literature
      study, which identifies wax and pectin removal to be the key steps for successful
      scouring process. Three main issues are discussed here, i.e. benchmarking of the
      existing alkaline scouring process, an evaluation of several selected acidic and
      alkaline pectinases for scouring, and the effect of wax removal treatment on
      pectinase performance. It has been found that the pectinolytic capability of
      alkaline pectinases on cotton pectin is nearly 75% higher than that of acidic
      pectinases. It is concluded that an efficient wax removal prior to pectinase
      treatment indeed results in improved performance in terms of hydrophilicity and
      pectin removal. To evaluate the hydrophilicity, the structural contact angle
      (theta) was measured using an auto-porosimeter.

PMID- 17219461
TI  - Fluorogenic substrates for lipases, esterases, and acylases using a TIM-mechanism
      for signal release.
AB  - 3-Acyloxyl-2-oxopropyl ethers of umbelliferone were investigated as new
      fluorogenic substrates for lipases and esterases. The aliphatic primary alcohol
      leaving group released the fluorescent product umbelliferone by an
      enolization/beta-elimination reaction similar to the triose phosphate isomerase
      (TIM) reaction. A similarly designed phenylacetamide provided a fluorescent probe
      for penicillin G acylase, whereby the enolization/beta-elimination sequence from
      the intermediate aminoketone was very fast and spontaneous even under acidic
      conditions. The corresponding epoxyketone was not fluorogenic with epoxide
      hydrolases (EH). These substrates represent periodate-free Clips-otrade mark
      substrates.

PMID- 17219463
TI  - Hospital medicine: an important player in comprehensive care.

PMID- 17219464
TI  - Palliative care and hospitalists: a partnership for hope.

PMID- 17219465
TI  - Effectiveness of ceftriaxone plus doxycycline in the treatment of patients
      hospitalized with community-acquired pneumonia.
AB  - BACKGROUND: Limited data exist on the effectiveness of ceftriaxone plus
      doxycycline in the treatment of patients hospitalized with community-acquired
      pneumonia (CAP). METHODS: We performed a retrospective cohort study of all adults
      hospitalized for pneumonia between January 1999 and July 2001 at an academic
      medical center. Outcomes were compared for patients with CAP treated with
      ceftriaxone plus doxycycline versus other appropriate initial empiric antibiotic
      therapies. Outcomes were adjusted with the use of a propensity score to account
      for differences in patient characteristics and illness severity between groups.
      RESULTS: A total of 216 patients were treated with ceftriaxone plus doxycycline
      and 125 received other appropriate initial empiric antibiotic therapies. After
      adjustment, use of ceftriaxone plus doxycycline was associated with reduced
      inpatient mortality (OR = 0.26, 95% CI: 0.08-0.81) and 30-day mortality (OR =
      0.37, 95% CI: 0.17-0.81), but not with length of stay or readmission rates.
      Analysis of a subset of the sample that excluded patients admitted from nursing
      homes, patients admitted to the ICU, and patients diagnosed with aspiration also
      showed reduced inpatient mortality with the use of ceftriaxone plus doxycycline.
      CONCLUSIONS: The use of ceftriaxone plus doxycycline as an initial empiric
      therapy for patients hospitalized with CAP appears safe and effective, and its
      potential superiority should be evaluated prospectively.

PMID- 17219466
TI  - Hospital-acquired gastrointestinal bleeding outside the critical care unit: risk
      factors, role of acid suppression, and endoscopy findings.
AB  - BACKGROUND: Risk factors for hospital-acquired gastrointestinal bleeding in the
      intensive care unit are established, and acid-suppressive prophylaxis has been
      advocated for certain subsets of critically ill patients. In contrast, risk
      factors and appropriate prevention strategies are not yet established for general
      medical patients. The objective of this study was to identify risk factors for
      nosocomial gastrointestinal bleeding (GIB) in non-critically ill medical
      patients, to evaluate the utility of prophylactic gastric acid suppression, and
      to characterize the endoscopic lesions. METHODS: This was a retrospective case
      control study that took place at a U.S. tertiary care center. All patients
      admitted to the General Medicine ward for nongastrointestinal disorders who
      developed clinically relevant gastrointestinal bleeding during admission or
      within 4 weeks of discharge were considered cases. Clinically relevant bleeding
      was defined as any bleeding requiring esophagogastroduodenoscopy (EGD). Random
      controls were matched to cases by date of hospitalization in a 1:1 ratio.
      Clinical information was extracted by chart review. RESULTS: Of 17,707 patients
      admitted to the General Medicine ward over a 4-year period, 73 (0.41%) met the
      case definition. The main risk factor for nosocomial GIB was treatment with full
      dose anticoagulants or clopidogrel (OR = 5.4; 2.6-11.7; P < .0001). Use of
      aspirin, nonsteroidal anti-inflammatory medications, and glucocorticoids did not
      differ significantly between cases and controls. De novo acid-suppressive
      prophylaxis was not protective (OR = 1.0; 95% CI: 0.4-2.4; P = 0.97). Endoscopic
      abnormalities were noted in 74% of patients; many cases had lesions unlikely to
      be prevented by acid blockade. CONCLUSIONS: Hospital-acquired gastrointestinal
      bleeding is uncommon in non-critically ill patients. Anticoagulation appears to
      be the most important risk factor for nosocomial GIB. Routine use of acid
      suppressant medications for prophylaxis is unnecessary in most hospitalized
      patients.

PMID- 17219467
TI  - Palliative care in hospitals.
AB  - Palliative care is medical care focused on the relief of suffering and support
      for the best possible quality of life for patients facing serious, life
      threatening illness and their families. It aims to identify and address the
      physical, psychological, and practical burdens of illness. Palliative care may be
      delivered simultaneously with all appropriate curative and life-prolonging
      interventions. In practice, palliative care practitioners provide assessment and
      treatment of pain and other symptom distress; employ communication skills with
      patients, families, and colleagues; support complex medical decision making and
      goal setting based on identifying and respecting patient wishes and goals; and
      promote medically informed care coordination, continuity, and practical support
      for patients, family caregivers, and professional colleagues across healthcare
      settings and through the trajectory of an illness. The field of hospital
      palliative care has grown rapidly in recent years in response to patient need and
      clinician interest in effective approaches to managing chronic life-threatening
      illness. The growth in the number and needs of seriously and chronically ill
      patients who are not clearly terminally ill has led to the development of
      palliative care services outside the hospice benefit provided by Medicare (and
      other insurers). This article reviews the clinical, educational, demographic, and
      financial imperatives driving this growth, describes the clinical components of
      palliative care and the range of service models available, defines the relation
      of hospital-based palliative care to hospice, summarizes the literature on
      palliative care outcomes, and presents practical resources for clinicians seeking
      knowledge and skills in the field.

PMID- 17219468
TI  - Is there a geriatrician in the house? Geriatric care approaches in hospitalist
      programs.
AB  - BACKGROUND: The rapid growth of the hospitalist movement presents an opportunity
      to reconsider paradigms of care for hospitalized older patients. METHODS: To
      determine the impact of the hospitalist movement on acute care geriatrics, we
      conducted a cross-sectional survey of the hospitalist community in 2003 and 2004.
      RESULTS: We identified innovations in geriatric hospital care in only 11
      hospitalist programs. These innovations varied widely in complexity, goals,
      structure, and staffing. The majority targeted patients using age as a criterion
      and incorporated geriatrics training for nurses or physicians. Several
      innovations had one or more of the following features: geriatrician-hospitalists
      or gerontology nurse-practitioners, perioperative management for complex older
      patients, specialized geriatric services such as skilled nursing units or acute
      care for elders units, and quality improvement initiatives targeted to the older
      patient. A case study of the Hospital Internal Medicine group at the Mayo Clinic
      is presented as an example of a complex innovation highlighting several of these
      features. CONCLUSIONS: The scarcity of geriatric care approaches among
      hospitalist groups highlights the need for collaboration between hospitalists and
      geriatricians, with the goals of rethinking staffing models and organization of
      care and focusing on quality-improvement activities. In particular, perioperative
      care and postdischarge care are two clinical areas where innovation in hospital
      care may particularly benefit older patients. Significant opportunities remain
      for collaboration, coordination, and research to improve the care of acutely ill
      older patients at the intersection of geriatric and hospital medicine.

PMID- 17219469
TI  - "Above or below?".

PMID- 17219470
TI  - Care of hospitalized older patients: opportunities for hospital-based physicians.
AB  - BACKGROUND: Half of patients admitted to hospital for reasons unrelated to
      childbirth are age 65 years or older. Nonetheless, few hospital-based physicians
      have received training in geriatric medicine, and few geriatricians practice in
      the hospital. This paper describes the state of the science of hospital care for
      older patients, and identifies opportunities and barriers to improving their
      care. METHODS: General medical journals from 1980 to the present were selectively
      reviewed to identify original articles on the treatment of specific diseases and
      syndromes on hospitalized persons age 65 years or older. Information was
      synthesized to describe the course of these patients during and after
      hospitalization, and to identify effective management strategies and gaps in
      knowledge. RESULTS: Older persons in hospitals pose substantial clinical
      challenges: they have high rates of cognitive impairment, delirium, disability,
      and difficulty walking, and they often require increased attention, longer
      lengths of stay, and higher hospital costs than younger patients with the same
      diagnoses. Disease-specific interventions have not been studied extensively in
      those older than 75 years. Multicomponent interventions can reduce short-term
      rates of disability and delirium without increasing costs, but they have not been
      widely disseminated. Interventions to treat or prevent other common conditions in
      hospitalized older patients have not been proven effective. CONCLUSIONS:
      Fundamental discoveries in the science of hospital medicine are needed to prevent
      or treat geriatric syndromes, to treat common diseases in the very old, and to
      put into practice what is known. Hospital-based physicians can address these gaps
      in knowledge and practice with geriatricians, building from their shared
      perspectives on the care of the aged in complex health systems.

PMID- 17219471
TI  - Core competencies in hospital medicine: development and methodology.
AB  - BACKGROUND: The hospitalist model of inpatient care has been rapidly expanding
      over the last decade, with significant growth related to the quality and
      efficiency of care provision. This growth and development have stimulated a need
      to better define and characterize the field of hospital medicine. Training and
      developing curricula specific to hospital medicine are the next step in the
      evolution of the field. METHODS: The Core Competencies in Hospital Medicine: A
      Framework for Curriculum Development (the Core Competencies), by the Society of
      Hospital Medicine, introduces the expectations of hospitalists and provides an
      initial structural framework to guide medical educators in developing curricula
      that incorporate these competencies into the training and evaluation of students,
      clinicians-in-training, and practicing hospitalists. This article outlines the
      process that was undertaken to develop the Core Competencies, which included
      formation of a task force and editorial board, development of a topic list, the
      solicitation for and writing of chapters, and the execution of multiple reviews
      by the editorial board and both internal and external reviewers. RESULTS: This
      process culminated in the Core Competencies document, which is divided into three
      sections: Clinical Conditions, Procedures, and Healthcare Systems. The chapters
      in each section delineate the core knowledge, skills, and attitudes necessary for
      effective inpatient practice while also incorporating a systems organization and
      improvement approach to care coordination and optimization. CONCLUSIONS: These
      competencies should be a common reference and foundation for the creation of
      hospital medicine curricula and serve to standardize and improve inpatient
      training practices.

PMID- 17219472
TI  - How to use The Core Competencies in Hospital Medicine: a framework for curriculum
      development.
AB  - BACKGROUND: The seminal article that coined the term hospitalist, published in
      1996, attributed the role of the hospitalist to enhancing throughput and cost
      reduction, primarily through reduction in length of stay, accomplished by having
      a dedicated clinician on site in the hospital. Since that time the role of the
      hospitalist has evolved, and hospitalists are being called upon to demonstrate
      that they actually improve quality of care and the education of the next
      generation of physicians. A companion article in this issue describes in detail
      the rationale for the development of the Core Competencies document and the
      methods by which it was created. METHODS: Specific cases that hospitalists may
      encounter in their daily practice are used to illustrate how the Core
      Competencies can be applied to curriculum development. The cases illustrate 1) a
      specific problem and the need for improvement; 2) a needs assessment of the
      targeted learners (hospitalists and clinicians in training); 3) goals and
      specific measurable objectives; 4) educational strategies using the competencies
      to provide structure and guidance; 5) implementation (applying competencies to a
      variety of training opportunities and curricula); 6) evaluation and feedback; and
      7) remaining questions and the need for additional research. RESULTS: This
      article illustrates how to utilize The Core Competencies in Hospital Medicine to
      educate trainees and faculty, to prioritize educational scholarship and research
      strategies, and thus to improve the care of our patients. CONCLUSIONS: Medical
      educators should compare their learning objectives to the Core Competencies to
      ensure that their trainees have achieved competency to practice hospital medicine
      and improve the hospital setting.

PMID- 17219473
TI  - Can't buy him love.

PMID- 17219474
TI  - Hospitals foreign soil for those who don't work there.

PMID- 17219476
TI  - The status of hospital medicine groups in the United States.
AB  - BACKGROUND: Hospitalists, defined as hospital-based physicians who take
      responsibility for managing the medical needs of inpatients, represent a
      significant trend in physician specialization. However, only limited anecdotal
      data quantifying the status of hospital medicine groups around the country is
      available. OBJECTIVE: To better understand the extent and nature of the
      hospitalist movement, utilizing data from the 2003 Annual Survey of the American
      Hospital Association (AHA). STUDY POPULATION: 4895 acute care hospitals in the
      United States. MEASUREMENTS: Number and percentage of hospitals with hospital
      medicine groups; mean number of hospitalists per group; hospitalists per average
      daily census (ADC) of 100 patients; distribution of groups by employment model.
      DESCRIPTIVE VARIABLES: Census region; rural/urban status; number of beds;
      organizational control; teaching status. RESULTS: There are approximately 1415
      hospital medicine groups and 11,159 hospitalists in the United States. The
      overall penetration of hospital medicine groups at hospitals is 29% (55% at
      hospitals with 200 or more beds), and the in-hospital impact at hospitals with
      hospital medicine groups is 3.93 hospitalists per 100 ADC. The average hospital
      medicine group has 7.9 hospitalists. There is a fairly equal distribution among
      the 3 major employment models for hospital medicine groups: hospital employees,
      independent provider groups, and physician groups. All these measures can vary
      substantially, depending on the characteristics of individual hospitals.
      CONCLUSIONS: Hospital medicine appears to have become part of the mainstream
      delivery of health care in the United States. No employment model of hospital
      medicine group appears to dominate this specialty. We expect there will continue
      to be growth and diversity in the implementation of hospital medicine groups.

PMID- 17219477
TI  - Impact of reliance on CT pulmonary angiography on diagnosis of pulmonary
      embolism: a Bayesian analysis.
AB  - BACKGROUND: Spiral computed tomographic pulmonary angiography (CTPA) has become
      the primary test used to investigate suspected pulmonary embolism (PE) at many
      institutions, despite uncertainty regarding its sensitivity and specificity.
      Although CTPA-based diagnostic algorithms focus on minimizing the false-negative
      rate, we hypothesized that increasing use of CTPA also might lead to false
      positive diagnoses. OBJECTIVE: Determine the frequency of possible false-positive
      diagnoses of PE when CTPA is the primary diagnostic test. DESIGN: Retrospective
      cohort study. SETTING: Two academic teaching hospitals. PARTICIPANTS: 322
      patients with suspected PE evaluated with CTPA. MEASUREMENTS: We used a validated
      prediction rule to determine the pretest probability of PE in each patient. We
      combined these pretest probabilities with published estimates of CTPA test
      characteristics to generate expected posttest probabilities of PE. We compared
      these posttest probabilities to actual treatment decisions to determine the rate
      of false-positive diagnoses of PE. RESULTS: Among 322 patients investigated for
      PE, 37 (12%) had high pretest probability, 101 (32%) moderate, and 184 (57%) low.
      CT scans were interpreted as positive for PE in 57 patients (17.8%). Regardless
      of the pretest probability of PE, 96.5% of patients with a positive CTPA were
      treated with anticoagulants. Even under an optimistic assumption of CTPA test
      characteristics, as many as 25.4% of these patients may have been treated
      unnecessarily as a result of a false-positive diagnosis. Most of these patients
      had a low pretest probability of PE. CONCLUSIONS: Failure to utilize Bayesian
      reasoning when interpreting CTPA may lead to false-positive diagnoses of
      pulmonary embolism in a substantial proportion of patients.

PMID- 17219478
TI  - How hospitalists spend their time: insights on efficiency and safety.
AB  - BACKGROUND: Despite the dramatic growth of hospitalists, no studies have
      evaluated the type and frequency of activities that hospitalists perform. To
      evaluate the types and frequency of activities that hospitalists perform during
      routine work, we conducted a time-motion study of hospitalist physicians at our
      institution. DESIGN: A research assistant shadowed hospitalist physicians for 3-
      to 5-hour periods. Observation periods were distributed in order to sample all
      parts of a typical day of a hospitalist, including both admitting and
      nonadmitting periods. Activities were recorded on a standardized data collection
      form in 1-minute intervals. Incoming pages were recorded as well. RESULTS: Ten
      hospitalists were shadowed by a single research assistant for a total of 4467
      minutes. Hospitalists spent 18% of their time on direct patient care, 69% on
      indirect patient care, 4% on personal activities, and 3% each on professional
      development, education, and travel. Communication accounted for 24% of the total
      minutes. Multitasking, performing more than one activity at the same time, was
      done 21% of the time. Hospitalists received an average of 3.4 +/- 1.5 pages per
      hour. CONCLUSIONS: Hospitalists spent most of their time on indirect patient care
      activities and relatively little time on direct patient care. Hospitalists spent
      a large amount of time on communication, underscoring the need for hospitalists
      to have outstanding communication skills and systems that support efficient
      communication. Multitasking and paging interruptions were common. The inherent
      distraction caused by interruptions and multitasking is a potential contributor
      to medical error and warrants further study.

PMID- 17219479
TI  - Acute aortic dissection.
AB  - Acute aortic dissection is an uncommon but lethal cause of acute chest, back, and
      abdominal pain. Establishing a timely diagnosis is paramount, as mortality from
      acute aortic dissection rises by the hour. Physical findings are protean and may
      include acute aortic valve insufficiency, peripheral pulse deficits, a variety of
      neurologic deficits, or end-organ ischemia. The keys to establishing a timely
      diagnosis are maintaining a high index of suspicion and quickly obtaining a
      diagnostic study. CT angiography, magnetic resonance imaging, transesophageal
      echocardiography, and, to a lesser extent, aortography are all highly accurate
      imaging modalities. The choice of study should be driven by the clinical
      stability of the patient, the information required and the resources available at
      presentation. Proximal dissections are surgical emergencies, but distal
      dissections are generally treated medically. Endovascular stents are gaining
      favor for use in the repair of both acute and chronic distal dissections. Long
      term outcome data for endovascular stenting are still limited, and it remains
      unclear when stenting should be favored over surgery or medical therapy.

PMID- 17219480
TI  - Routine rapid HIV testing in hospitals: another opportunity for hospitalists to
      improve care.
AB  - BACKGROUND: The Centers for Disease Control and Prevention recommends routinely
      offering HIV testing to inpatients at hospitals with an HIV seroprevalence rate
      of greater than 1% or an AIDS diagnosis rate of greater than 1.0 per 1000
      discharges. This recommendation has not been widely adopted, perhaps because of
      one of several barriers: the cost of implementing a counseling and testing
      program; the logistics of HIV counseling and testing on a hospital ward
      particularly with respect to privacy; concern about the follow-up of HIV test
      results necessitating patients to return after discharge; and the cultural
      mindset of screening as an outpatient modality complicated by the fear of raising
      the possibility of HIV testing and therefore eliciting a negative reaction from a
      patient who has not requested it. PURPOSE: This article focuses on these barriers
      and some possible solutions, emphasizing the role of FDA-approved rapid HIV
      tests, which may decrease follow-up issues for HIV testing programs. It also
      considers hospitalists, given their frontline status and ability to coordinate
      the multidisciplinary services and system-wide approach required to implement
      such a program, as leaders in this area.

PMID- 17219481
TI  - A negative test of aneurysmal proportions.

PMID- 17219482
TI  - Pandemic influenza and the hospitalist: apocalypse when?
AB  - Beginning with a cluster of human cases in Hong Kong in 1997, avian influenza
      (H5N1) has spread progressively through, and beyond, Asia in poultry and other
      birds; and has resulted in sporadic cases of human disease associated with high
      mortality. The potential for H5N1 influenza to cause a pandemic of human disease
      continues to be the subject of intense scrutiny by both the media and the
      scientific community. While the likelihood of such a prospect is uncertain, the
      inevitability of future pandemics of influenza is clear. Planning for the
      eventuality of a virulent influenza pandemic at the local, national and global
      level is critical to limiting the mortality and morbidity of such an occurrence.
      Hospitalists have a key role to play in institutional efforts to prepare for a
      influenza pandemic, and should be aware of lessons that my be applied from both
      the response to Hurricane Katrina, as well as the severe acute respiratory
      syndrome (SARS) epidemic.

PMID- 17219483
TI  - Curriculum development: the venous thromboembolism quality improvement resource
      room.
AB  - BACKGROUND: The role of the hospitalist has evolved over the last decade, with
      hospitalists increasingly being asked to lead systems-based initiatives to
      improve the quality of inpatient care. The educational strategy of the Society of
      Hospital Medicine (SHM) includes development of practice-based resources to
      support hospitalist-led improvement in clinically important measures of hospital
      care quality. OBJECTIVE: To develop a resource at the SHM Web site to present
      quality improvement (QI) principles for systems-based care in the hospital and to
      help individual hospitalists improve specific patient outcomes. DESIGN: The SHM
      defined the role of the hospitalist in QI, performed an assessment of the
      educational needs of hospitalists, and executed a Web-based educational strategy
      to address these needs. The organization identified the most common cause of
      preventable inpatient deaths, hospital-acquired venous thromboembolism (VTE), and
      prioritized the need to improve prophylaxis. RESULTS: This new resource at the
      SHM Web site presents principles for conducting QI in the hospital. To enable
      learning that is practice based, the VTE Quality Improvement Resource Room (QI
      RR) features Ask the Expert, an interactive discussion community, and an original
      Improvement Workbook, a downloadable project outline and tutorial that
      hospitalists can use to guide and document steps in an effort aimed at reducing
      hospital-acquired VTE. CONCLUSIONS: This QI resource serves as a template for the
      development of subsequent hospital-based resources. User feedback will refine the
      QI RR and its format so that similar offerings can target other significant
      inpatient problems. Additional research is needed to evaluate learning and the
      clinical impact of this quality improvement resource on hospital performance
      measures and patient outcomes.

PMID- 17219484
TI  - Death is a crafty adversary.

PMID- 17219485
TI  - Uncharted waters.

PMID- 17219487
TI  - Glycemic chaos (not glycemic control) still the rule for inpatient care: how do
      we stop the insanity?

PMID- 17219488
TI  - Inpatient management of diabetes and hyperglycemia among general medicine
      patients at a large teaching hospital.
AB  - BACKGROUND: Because of the relationship between inpatient hyperglycemia and
      adverse patient outcomes, current guidelines recommend glucose levels less than
      180 mg/dL in the non-ICU inpatient setting and the use of effective insulin
      protocols for appropriate patients. OBJECTIVE: To determine the current state of
      glucose management on an academic hospitalist service and the relationship
      between insulin-ordering practices and glycemic control. DESIGN: Prospective
      cohort study. SETTING: Hospitalist-run general medicine service of an academic
      teaching hospital. PATIENTS: 107 consecutive patients with diabetes mellitus or
      inpatient hyperglycemia. MEASUREMENTS: We collected data on up to 4 bedside
      glucose measurements per day, detailed clinical information, and all orders
      related to glucose management. The primary outcomes were rate of hyperglycemia
      (glucose > 180 mg/dL) per patient and mean glucose level per patient-day.
      RESULTS: The mean rate of hyperglycemia was 31% of measurements per patient.
      Basal insulin was ordered for 43% of patients, and scheduled rapid- or short
      acting insulin was ordered for 4% of patients. Sixty-five percent of patients who
      had at least 1 episode of hyper- or hypoglycemia had no change made to any
      insulin order during the first 5 days of the hospitalization. When adjusted for
      clinical factors, the use of sliding-scale insulin by itself was associated with
      a 20 mg/dL higher mean glucose level per patient-day. CONCLUSIONS: Management of
      diabetes and hyperglycemia on a general medicine service showed several
      deficiencies in process and outcome. Possible targets for improvement include
      increased use of basal and nutritional insulin and daily insulin adjustment in
      response to hyperglycemia.

PMID- 17219489
TI  - Diabetes care in the hospital: is there clinical inertia?
AB  - BACKGROUND: Effective control of hospital glucose improves outcomes, but little
      is known about hospital management of diabetes. OBJECTIVE: Assess hospital-based
      diabetes care delivery. DESIGN: Retrospective chart review. SETTING: Academic
      teaching hospital. PATIENTS: Inpatients with a discharge diagnosis of diabetes or
      hyperglycemia were selected from electronic records. A random sample (5%, n = 90)
      was selected for chart review. MEASUREMENTS: We determined the percentage of
      patients with diabetes or hyperglycemia documented in admission, daily progress,
      and discharge notes. We determined the proportion of cases with glucose levels
      documented in daily progress notes and with changes in hyperglycemia therapy
      recorded. The frequency of hypoglycemic and hyperglycemic events was also
      determined. RESULTS: A diabetes diagnosis was recorded at admission in 96% of
      patients with preexisting disease, but daily progress notes mentioned diabetes in
      only 62% of cases and 60% of discharge notes; just 20% of discharges indicated a
      plan for diabetes follow-up. Most patients (86%) had bedside glucose measurements
      ordered, but progress notes tracked values for only 53%, and only 52% had a
      documented assessment of glucose severity. Hypoglycemic events were rare (11% of
      patients had at least one bedside glucose < 70 mg/dL), but hyperglycemia was
      common (71% of cases had at least one bedside glucose > 200 mg/dL). Despite the
      frequency of hyperglycemia, only 34% of patients had their therapy changed.
      CONCLUSIONS: Practitioners were often aware of diabetes at admission, but the
      problem was often overlooked during hospitalization. The low rate of
      documentation and therapeutic change suggests the need for interventions to
      improve provider awareness and enhance inpatient diabetes care.

PMID- 17219490
TI  - If asked, hospitalized patients will choose whether to receive life-sustaining
      therapies.
AB  - BACKGROUND: No national policy requires health care providers to discuss with
      hospitalized patients whether the latter would want cardiopulmonary resuscitation
      (CPR) or mechanical ventilation (MV) in the event of cardiopulmonary failure.
      OBJECTIVE: To determine whether hospitalized patients are willing to discuss end
      of-life issues and choose whether to receive CPR and MV. DESIGN: Prospective
      randomized trial. PARTICIPANTS: 297 patients admitted to the medicine service of
      a 350-bed community teaching hospital. INTERVENTION: Patients were randomized to
      receive routine care or a scripted intervention, delivered by research
      physicians, that included detailed information about CPR, MV, and advance
      directives. MEASUREMENTS: Number of patients who welcomed the scripted
      intervention, number who chose to receive or reject CPR/MV, and number of advance
      directives created during hospitalization. RESULTS: Of the 297 patients studied,
      136 were in the intervention group and 161 were in the control group. Baseline
      characteristics and severity of illness were similar in the 2 groups. Of the 136
      patients in the intervention group, 133 (98%) willingly discussed CPR and
      mechanical ventilation, and 112 (82%) found the information useful. One hundred
      and twenty-five (92%) clarified their preferences regarding CPR and MV after
      receiving the intervention; of the 48 patients who were initially documented as
      wanting CPR/MV, 3 requested no CPR/MV after the intervention. Of the 87 patients
      in the intervention group who had no documentation of code status on admission, 5
      asked for no CPR/MV. Of the 161 patients in the control group, 55 had
      documentation of their code status on admission. Of the 106 patients without
      documentation, 6 were later documented to receive no CPR/MV. Thirteen of the 102
      patients who had no advance directive on admission created one after the
      intervention, whereas only 1 of the 128 patients in the control group did so (P <
      .001). CONCLUSIONS: Patients are willing to discuss and give informed consent for
      CPR and mechanical ventilation early in hospitalization. Only a minority drafted
      advance directives during hospitalization. Larger studies that include patients
      at other centers are required to determine whether these findings are
      reproducible and whether this approach is clinically feasible.

PMID- 17219491
TI  - Cost utility of substituting enoxaparin for unfractionated heparin for
      prophylaxis of venous thrombosis in the hospitalized medical patient.
AB  - BACKGROUND: Both heparin and enoxaparin are effective for the prevention of
      venous thromboembolism (VTE) in medical patients. On the basis of price, heparin
      appears preferable because it is less expensive. However, choosing enoxaparin may
      have greater cost utility when the outcomes of heparin-induced thrombocytopenia
      (HIT) and heparin-induced thrombocytopenia with thrombosis (HITT) are considered.
      OBJECTIVE: To determine the cost utility of substituting enoxaparin for heparin
      from payer and institutional perspectives. DESIGN: A decision analysis model was
      used. Cost data were based on Medicare reimbursement and the medication and
      laboratory costs for a multi-institutional healthcare system. Quality-adjusted
      life years (QALYs) saved by preventing HIT/HITT through the use of enoxaparin
      were based on published data. Costs are expressed on a per-day basis, and the
      incremental cost of enoxaparin over that of heparin was used in the calculation
      of cost/QALY. A sensitivity analysis also was performed. SETTING: Inpatient
      medicine. PATIENTS: All medical patients for whom VTE prophylaxis was
      appropriate. INTERVENTIONS: Substitution of enoxaparin for heparin. MEASUREMENT:
      Cost/QALY. RESULTS: From a payer perspective, using enoxaparin resulted in a
      decrease in cost of 28.61 dollars over that of heparin and saved 0.00629 QALYs in
      the base case, resulting in a savings of 4550.17 dollars/QALY. The sensitivity
      analysis showed this finding of decreased cost and increased effectiveness to be
      consistent. From an institutional perspective, the use of heparin generally
      appeared less costly but was dependent on medication price, length of stay
      required, and bed utilization. CONCLUSIONS: From a payer and, by extrapolation, a
      societal perspective, cost-utility analysis supports the use of enoxaparin in
      place of heparin for the prevention of VTE in medical inpatients. From an
      institutional perspective, the decision is more complicated, but in most cases,
      the use of enoxaparin also is supported.

PMID- 17219492
TI  - Community-acquired pneumonia: a practical approach to management for the
      hospitalist.
AB  - Community-acquired pneumonia (CAP) is common, and inpatient physicians should be
      familiar with the most current evidence about and guidelines for CAP management.
      Our conclusions and recommendations include: Streptococcus pneumoniae is the most
      common identified cause of CAP requiring hospitalization, whereas Legionella
      pneumophila is a common cause of severe CAP. The chest radiograph remains an
      essential initial test in the diagnosis of CAP and should be supplemented by
      blood cultures sampled prior to antibiotic therapy and sputum for gram stain and
      culture if a high-quality specimen can be rapidly processed. Once the diagnosis
      is made, the Pneumonia Severity Index (PSI) should be used to optimize the
      location of treatment and to provide prognostic information. Absent other
      mitigating factors, patients in PSI risk classes I, II, and III can safely be
      treated as outpatients. Hospitalized patients with CAP should be treated promptly
      with empiric antibiotics. Nonsevere pneumonia should be treated with a parenteral
      beta-lactam plus either doxycycline or a macrolide. Patients admitted to the
      intensive care unit should be treated with a beta-lactam plus either a macrolide
      or a fluoroquinolone as well as be evaluated for pseudomonal risk factors. Most
      patients with nonsevere CAP reach clinical stability in 2-3 days and should be
      considered for a switch to oral therapy and discharge shortly thereafter.
      Patients should receive pneumococcal vaccination, influenza vaccination, and
      tobacco cessation counseling prior to discharge if eligible. Multiple quality
      indicators are measured and publicly reported in the management of CAP, which
      provides hospitals with an opportunity to improve care processes and patient
      outcomes.

PMID- 17219493
TI  - Lean health care: what can hospitals learn from a world-class automaker?
AB  - BACKGROUND: With health care costs continuing to rise, a variety of process
      improvement methodologies have been proposed to address the reported
      inefficiencies in health care delivery. Lean production is one such method. The
      management philosophy and tools of lean production come from the manufacturing
      industry, where they were pioneered by Toyota Motor Corporation, which is viewed
      as the leader in utilizing these performance improvement methods. Lean has
      already enjoyed tremendous success in improving quality and efficiency in both
      the manufacturing and the service sector industries. RESULTS: Health care systems
      have just begun to utilize lean methods, with reports of improvements just
      beginning to appear in the literature. We describe some of the basic philosophy
      and principles of lean production methods and how these concepts can be applied
      in the health care environment. We describe some of the early success stories and
      ongoing endeavors of lean production in various health care organizations. We
      believe the hospital is an ideal setting for use of the lean production method,
      which could significantly affect how health care is delivered to patients.
      CONCLUSIONS: We conclude by discussing some of the potential challenges in
      introducing and implementing lean production methods in the health care
      environment. Lean production is a novel approach to delivering high-quality and
      efficient care to patients, and we believe that the health care sector can
      anticipate the same high level of success that the manufacturing and service
      industries have achieved using this approach. Hospitalists are primed to take
      action in delivering care of greater quality with more efficiency by applying
      these new principles in the hospital setting.

PMID- 17219494
TI  - A midlife crisis.

PMID- 17219495
TI  - Heroes.

PMID- 17219497
TI  - Our last date.

PMID- 17219499
TI  - Hospitalists and geriatrics.

PMID- 17219500
TI  - Universal acceptance of computerized physician order entry: what would it take?

PMID- 17219502
TI  - Lipid assessment and treatment patterns in hospitalized TIA and ischemic stroke
      patients.
AB  - BACKGROUND: Identification of dyslipidemia and treatment with lipid-lowering
      agents are established targets for quality performance during hospitalization for
      ischemic stroke and transient ischemic attack (TIA). We aimed to study the
      frequency and predictors of lipid assessment and discharge utilization of lipid
      lowering therapies among patients hospitalized for stroke and TIA. METHODS:
      Demographics, clinical findings, and laboratory data were documented as part of
      the California Acute Stroke Prototype Registry (CASPR). Frequency of low-density
      lipoprotein cholesterol (LDL-C) testing and the frequency and appropriate use of
      lipid-lowering treatment according to national cholesterol guidelines were
      determined. Multivariate models were generated to determine the contribution of
      clinical variables to LDL testing and prescription of lipid-lowering medications
      at discharge. RESULTS: Data were collected on 764 consecutive patients with
      ischemic stroke or TIA treated at 11 hospitals over a 2-year period. LDL-C
      measurements were performed in only 50.1% during hospitalization. Measurement of
      LDL-C was most strongly and independently associated with diagnosis of ischemic
      stroke (vs. TIA, P = .02) and history of dyslipidemia (P = .05). Overall, 48.4%
      of the CASPR cohort received lipid-lowering medications at discharge. Independent
      predictors for being prescribed lipid-lowering agents at discharge were diagnosis
      of ischemic stroke (P = .0009), LDL-C testing (P = .0002), high risk of future
      coronary events according to national guidelines (P = .02), and history of
      dyslipidemia (P< .0001). Only 59% of patients at high risk for future coronary
      events were discharged on a lipid-lowering medication. CONCLUSIONS: Serum
      cholesterol testing and treatment are underutilized during hospitalization for
      ischemic stroke or TIA.

PMID- 17219503
TI  - Physician characteristics, attitudes, and use of computerized order entry.
AB  - BACKGROUND: Computerized physician order entry (CPOE) is a widely advocated
      patient safety intervention, yet little is known about its adoption by attending
      physicians or community hospitals. METHODS: We calculated the order entry rates
      of attending physicians at 2 hospitals by measuring the number of orders entered
      directly and dividing this by the sum of orders entered directly and those
      written by hand. These findings were paired with the results of a survey that
      assessed attitudes concerning the impact of CPOE on personal efficiency, quality
      of care, and patient safety. RESULTS: Three hundred and fifty-six (71%) of the
      502 surveys were returned by physicians, whose median order entry rate was 66%.
      Forty-two percent of respondents placed at least 80% of their orders
      electronically (high use), 26% placed 21%-79% of their orders electronically
      (intermediate use), and 32% placed 20% or less of their orders electronically
      (low use). Sex, years since medical school graduation, years in practice at the
      study institution, and use of computers in the outpatient arena were not
      meaningfully different among the 3 groups. However, use of the system to place
      orders varied by specialty, and those with intermediate or high use of the system
      were more likely than low users to have used CPOE during training and to be
      regular users of computers for personal activities. These physicians were more
      likely to believe that CPOE enabled orders to be placed efficiently, that
      directly entered orders were carried out more rapidly, and that such orders were
      associated with fewer errors. CONCLUSIONS: The adoption of CPOE by attending
      physicians at community hospitals varies widely. In addition to purchasing
      systems that support physician work flow, hospitals intent on successfully
      implementing CPOE should emphasize the benefits in safety and quality of this new
      technology.

PMID- 17219504
TI  - Discussing resuscitation preferences with patients: challenges and rewards.
AB  - Discussing preferences regarding resuscitation is a challenging and important
      task for any physician. Understanding patients' wishes at the end of life allows
      physicians to provide the type of care patients want, to avoid unwanted
      interventions, and to promote patient autonomy and dignity. Hospitalists face an
      even greater challenge because they are often meeting a patient for the first
      time in a crisis situation. Despite the frequency with which clinicians have
      these conversations, they typically fall short when discussing code status with
      patients. In this evidence-based review, we discuss physician barriers to
      conducting effective discussions, offer a variety of approaches to enhancing
      these conversations, and review important communication techniques.

PMID- 17219505
TI  - More steroids or less? That is the question!

PMID- 17219506
TI  - Reflections: the hospitalist movement a decade later.
AB  - August 2006 marks the 10th anniversary of the publication of an article in the
      New England Journal of Medicine in which Lee Goldman and I coined the term
      hospitalist-an event that many people characterize as the start of the
      hospitalist movement in the United States. The present article describes the
      history of those early days, highlighting some of the choices the field's initial
      leaders made to nurture the new specialty. In retrospect, although there were
      many examples of fortunate serendipity, there were also several key strategic
      choices, including the focus on gathering research data to demonstrate the value
      of the field to external stakeholders; the forceful rejection of mandatory
      hospitalist systems, particularly those promoted by managed care organizations;
      and the purposeful linking of our new field to the burgeoning movements to
      improve quality and patient safety in hospitals. Most of all, the field's
      spectacular growth and successes can be attributed to the daily work of thousands
      of hospitalists in clinical care, education, research, and systems improvement.
      These individuals have given life to our theoretical notion a decade ago that a
      new model for inpatient care would improve the American health care system and
      the care of inpatients.

PMID- 17219507
TI  - AHRQ: present and future activities impacting hospital medicine.

PMID- 17219509
TI  - A tasty stew: a tale that changed my practice.

PMID- 17219508
TI  - Managing discontinuity in academic medical centers: strategies for a safe and
      effective resident sign-out.
AB  - BACKGROUND: Restrictions in the hours residents can be on duty have resulted in
      increased sign-outs, that is, transfer of patient care information and
      responsibility from one physician to a cross-coverage physician, leading to
      discontinuity in patient care. This sign-out process, which occurs primarily in
      the inpatient setting, traditionally has been informal, unstructured, and
      idiosyncratic. Although studies show that discontinuity may be harmful to
      patients, this is little data to assist residency programs in redesigning systems
      to improve sign-out and manage the discontinuity. PURPOSE: This article reviews
      the relevant medical literature, current practices in non-health professions in
      managing discontinuity, and summarizes the existing practice and experiences at 3
      academic internal medicine hospitalist-based programs. CONCLUSIONS: We provide
      recommendations and strategies for best practices to design safe and effective
      sign-out systems for residents that may also be useful to hospitalists working in
      academic and community settings.

PMID- 17219512
TI  - Analysis of strategies to improve cost effectiveness of blood cultures.
AB  - BACKGROUND: Approximately 90% of all blood cultures grow no organisms (ie, are
      true negatives), and 5% are thought to represent contaminants (ie, are false
      positives). The cost effectiveness of blood cultures could therefore be improved
      by developing rules that safely decreased the number of cultures drawn from
      patients with a low likelihood of having bacteremia and/or by improving the
      process of obtaining cultures, thereby decreasing the number of contaminants. We
      analyzed the potential effects of these two approaches. METHODS: We annualized
      the hospital costs and lengths of stay for patients with true-negative and false
      positive blood cultures from a retrospective analysis of 939 sets of cultures
      drawn in January 2002. RESULTS: Of the 939 blood culture sets, 816 (87%) were
      true negatives and generated annualized costs of approximately 750,000 dollars.
      Although only 56 (6%) of the blood culture sets were false positives, they
      resulted in annualized costs of 1.4-1.8 million dollars and added an estimated
      1450-2200 extra hospital days/year. CONCLUSIONS: Despite there being nearly 15
      times as many true-negative blood cultures as false positive ones, far greater
      improvements in resource utilization would result from reducing the number of
      contaminated blood cultures than by reducing the number of true negatives. The
      potential savings from this approach are of sufficient magnitude to justify
      investing considerable resources to attaining this goal.

PMID- 17219514
TI  - Evidence-based sepsis therapy: a hospitalist perspective.
AB  - BACKGROUND: Severe sepsis and septic shock are common and associated with a 30
      50% mortality rate. Evidence-based therapies for severe sepsis supported by
      international critical care and infectious disease societies exist, but are
      inconsistently employed. METHODS: The epidemiology and definitions of sepsis
      syndromes are reviewed; sepsis therapies supported by definitive studies in the
      field, along with the supporting literature, are summarized and presented from a
      hospitalist perspective. CONCLUSIONS: Compelling observational data supports the
      importance of early, effective antibiotics. Well-designed randomized controlled
      trials and/or meta-analyses demonstrate the impact of activated protein C, early
      goal-directed therapy, stress-dose steroids, and intensive insulin in well
      defined subgroups of patients. These therapies reduce the absolute mortality risk
      associated with severe sepsis by 9.5-16%; the corresponding numbers needed to
      treat to save one life are 6.25-10.5. While major trials are ongoing and the
      evidence for several sepsis therapies are limited to single trials, the available
      evidence indicates that appropriate use of these treatments can substantially
      reduce mortality from severe sepsis.

PMID- 17219513
TI  - Predictors of regaining ambulatory ability during hospitalization.
AB  - BACKGROUND: Loss of ambulatory ability with acute hospitalization is common and
      often does not improve by discharge. OBJECTIVES: To define admission predictors
      of regaining ambulatory ability during hospitalization in patients with expected
      activity limitations. DESIGN: Prospective cohort study. SETTING: University
      teaching hospital. PARTICIPANTS: Two hundred and eighty-six patients at least 55
      years of age whose activity was expected to be limited to a bed or chair for at
      least the first 5 days of hospitalization or who had a hip fracture, who were
      ambulatory in the 4 weeks prior to hospital admission, and whose length of stay
      in the hospital was less than 32 days. MEASUREMENTS: Baseline data collected from
      admission physician and nurse interviews and abstracted from the medical records
      included length of stay, demographic characteristics, global health measures,
      presence of specific diseases, and hospital-related factors hypothesized to
      affect ambulation. Nurses were asked weekly if patient activity was still
      expected to be limited to a bed or chair. RESULTS: Despite initially being
      limited to a bed or chair, 42% had regained ambulatory ability by discharge.
      Recovery of ambulatory ability was independently associated with not being
      married (odds ratio [OR] = 3.0, 95% confidence interval [CI] 1.4-6.2), higher
      physician-rated life expectancy (OR = 1.9, 95% CI 1.3-2.8), absence of restraints
      (OR = 2.5, 95% CI 1.2-5.5), having a urinary catheter (OR = 2.2, 95% CI 1.2-5.5),
      having deep vein thrombosis (OR = 11.4, 95% CI 1.2-105.1), and having a higher
      level of bed mobility at admission (OR = 1.7, 95% CI 1.1-2.6). CONCLUSIONS:
      Recovery of ambulatory ability is closely associated with physician-rated life
      expectancy and hospital-related factors, particularly those that affect mobility.
      Early recognition of who will recover ambulatory ability may help with discharge
      planning and potential interventions.

PMID- 17219515
TI  - Establishing a rapid response team (RRT) in an academic hospital: one year's
      experience.
AB  - BACKGROUND: Rapid response teams and medical emergency teams have been utilized
      to rapidly manage seriously ill patients at risk of cardiopulmonary arrest and
      other high-risk conditions but have not been extensively described in the
      American medical literature. OBJECTIVES: To describe a full year's experience of
      implementing a rapid response team (RRT) in an academic medical center. DESIGN:
      Retrospective analysis of our hospital's RRT database and description of the
      implementation process from July 2004 to July 2005. SETTING: Urban, academic
      medical center. RESULTS: The RRT system was activated for 307 potentially
      unstable patients. The most common reasons for an RRT activation were cardiac,
      respiratory, and neurological conditions. At least 37% of RRT calls were for off
      unit inpatients and to outpatient/common areas frequented by outpatients and
      visitors, whereas at least 42% occurred in inpatient units. Most RRT calls,
      82.9%, occurred during daytime hours. In the opinion of RRT leaders 98% of the
      evaluated calls were appropriate and 85% of the RRT responses resulted in the
      prevention of further clinical deterioration. CONCLUSIONS: An RRT was introduced
      into an academic medical center, and the results suggested it is capable of
      preventing clinical deterioration in unstable patients and may have the potential
      to decrease the frequency of cardiac arrests. The RRT also may fill a gap in
      patient safety by enabling rapid triage and expedited treatment of off-unit
      inpatients, outpatients, and visitors. The keys to the early success of our
      implementation of an RRT were multidisciplinary input and improvements made in
      real time.

PMID- 17219516
TI  - Don't just do something, stand there!

PMID- 17219517
TI  - Infected pneumatocele.

PMID- 17219518
TI  - A case of bronchopulmonary carcinoid tumor: the role of octreotide scanning in
      localization of an ectopic source of ACTH.
AB  - BACKGROUND: Bronchopulmonary carcinoids are neuroendocrine tumors. They can
      present with Cushing's syndrome secondary to ectopic adrenocorticotropic hormone
      (ACTH) secretion. Curative resection is possible only after adequate localization
      of the ectopic source. OBJECTIVE: To describe a case that illustrates the role of
      octreotide scanning in the management of a bronchopulmonary carcinoid. RESULTS:
      The use of preoperative and postoperative octreotide scanning aided in performing
      a limited resection, thereby preserving the lung parenchyma. CONCLUSIONS: We
      propose that octreotide scanning can be a very important and informative test in
      the management of carcinoid tumors. In situations when conventional imaging is
      not conclusive, octreotide scanning may be of help in determining the source of
      ectopic ACTH syndrome.

PMID- 17219519
TI  - Outpatient physicians' satisfaction with discharge summaries and perceived need
      for an electronic discharge summary.
AB  - BACKGROUND: Deficits in information transfer between inpatient and outpatient
      physicians are common and potentially dangerous. OBJECTIVE: To evaluate
      satisfaction with current discharge summaries, perceptions of preventable adverse
      events related to suboptimal information transfer, and the perceived need for the
      electronic discharge summary we plan to design. DESIGN AND PARTICIPANTS: : Survey
      of Department of Medicine physicians with an outpatient practice. MEASUREMENTS:
      Satisfaction with timeliness and quality of discharge summaries was assessed
      using a 5-point Likert scale. Respondents estimated the number of patients with
      preventable adverse events related to suboptimal information transfer at
      discharge. RESULTS: Of the 416 eligible respondents, 226 completed the survey
      (54%). Only 19% of the participants were satisfied or very satisfied with
      timeliness, and only 32% were satisfied or very satisfied with the quality of
      discharge summaries. Overall, 41% believed that at least 1 of their patients
      hospitalized in the previous 6 months had experienced a preventable adverse event
      related to poor transfer of information at discharge. CONCLUSIONS: Physicians
      were not satisfied with the timeliness or quality of discharge summaries.
      Physicians indicated that suboptimal transfer of information at hospital
      discharge contributed to preventable adverse events.

PMID- 17219522
TI  - Ghost story.

PMID- 17219524
TI  - The language of quality improvement: therapy classes.

PMID- 17219525
TI  - Improved use of thromboprophylaxis for deep vein thrombosis following an
      educational intervention.
AB  - BACKGROUND: We evaluated venous thromboembolism (VTE) prophylaxis rates in
      hospitalized medical patients in a teaching hospital, the State University of New
      York-Downstate Medical Center-University Hospital of Brooklyn, before and after
      implementation of a multifaceted VTE prophylaxis quality improvement intervention
      that combined regular education, dissemination of a decision support tool, and
      regular audit-and-feedback to resident physicians. METHODS: The charts of 312
      hospitalized medical patients were retrospectively reviewed to assess baseline
      rates of appropriate VTE prophylaxis. Rates of appropriate VTE prophylaxis were
      then determined 12 and 18 months after implementation of the quality improvement
      intervention. Data collected included risk factors for VTE, contraindications to
      anticoagulant prophylaxis, type of VTE prophylaxis prescribed, and whether the
      prophylaxis was appropriate. RESULTS: Most of the hospitalized medically ill
      patients had 3 or more risk factors for VTE. At baseline, the proportion of
      patients receiving any form of VTE prophylaxis, primarily unfractionated heparin,
      was 47%. The proportion of patients for whom a physician provided appropriate
      prophylaxis was 43%. After the intervention, the proportion of patients receiving
      prophylaxis significantly increased, to 86% at 12 months, and this level was
      maintained at 18 months. The rate of appropriate prophylaxis increased to 68% and
      85% after 12 and 18 months, respectively. CONCLUSIONS: The proportion of
      hospitalized medical patients receiving appropriate VTE prophylaxis as
      recommended by evidence-based guidelines can be increased significantly by
      combining regular education, a decision support tool, and regular audit-and
      feedback.

PMID- 17219526
TI  - What effect does an educational intervention have on interns' confidence and
      knowledge regarding acute dyspnea management? A randomized controlled trial.
AB  - BACKGROUND: Though acute dyspnea is commonly encountered in hospitalized
      patients, interns often receive only informal instruction in managing such
      patients. We hypothesized that formal instruction would improve interns'
      knowledge and confidence in managing patients with acute dyspnea. METHODS: Twenty
      six internal medicine interns were randomized to receive either standard
      education or standard education plus the educational intervention. The
      educational intervention included two small-group, case-based discussions on
      acute dyspnea management. All participants completed pre- and post-intervention
      surveys over four months that assessed their knowledge and confidence in managing
      patients with acute dyspnea. RESULTS: Of the 16 interns in the intervention
      group, 14 attended one of the two small-group sessions while seven attended both
      sessions. Mean confidence increased by 21.2% in the intervention group and 14.4%
      in the control group. The trend over time for both groups was significant (P <
      .001); the effect of the intervention was not (P = .19). Mean knowledge scores
      increased 7.6% in the intervention group and 5.5% in the control group. Again,
      the trend over time for both groups was significant (P < .01), but the effect of
      the intervention was not (P = .65). A per-protocol analysis revealed a trend
      toward significance with mean scores increasing 15.6% (P = .067). CONCLUSIONS:
      Our trial found that intern confidence and knowledge about acute dyspnea
      management increased significantly over time; however, no significant differences
      between the intervention and control groups were seen. The complete intervention
      was not administered to the majority of the intervention group, thereby skewing
      results to the null. The per-protocol analysis suggests attendance at educational
      sessions may improve knowledge. Future interventions should use a more sensitive
      testing instrument, a larger sample, and a more powerful intervention.

PMID- 17219527
TI  - Community-acquired pneumonia: defining quality care.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is one of 3 initial conditions for
      which the Joint Commission for Accreditation of Healthcare Organizations and the
      Centers for Medicare & Medicaid Services have defined quality measures. Eight
      "core measures" of pneumonia care have been targeted for reporting by U.S.
      hospitals to facilitate performance monitoring. METHODS: A review of the
      literature supporting the core measures was performed. RESULTS: Indicators
      encouraging influenza vaccination and appropriate antibiotic selection had the
      most robust evidence. Rapid delivery of antibiotics also showed significant
      reduction in mortality, though the actual timing (4 versus 8 hours) varied
      between studies. Other measures, such as performance of blood cultures,
      pneumococcal vaccination, smoking cessation, and oxygenation assessment,
      demonstrated less obvious clinical benefit. CONCLUSIONS: There is inherent value
      in setting standards of care for high-impact conditions such as CAP, but these
      standards should be chosen on the basis of high-quality research. Public
      reporting of the current measures is problematic, as it implies they represent
      best practices for CAP despite relatively weak evidence.

PMID- 17219529
TI  - A frayed knot.

PMID- 17219528
TI  - Transition of care for hospitalized elderly patients--development of a discharge
      checklist for hospitalists.
AB  - BACKGROUND: Discharge from the hospital is a critical transition point in a
      patient's care. Incomplete handoffs at discharge can lead to adverse events for
      patients and result in avoidable rehospitalization. Care transitions are
      especially important for elderly patients and other high-risk patients who have
      multiple comorbidities. Standardizing the elements of the discharge process may
      help to address the gaps in quality and safety that occur when patients
      transition from the hospital to an outpatient setting. METHODS: The Society of
      Hospital Medicine's Hospital Quality and Patient Safety committee assembled a
      panel of care transition researchers, process improvement experts, and
      hospitalists to review the literature and develop a checklist of processes and
      elements required for ideal discharge of adult patients. The discharge checklist
      was presented at the Society of Hospital Medicine's Annual Meeting in April 2005,
      where it was reviewed and revised by more than 120 practicing hospitalists and
      hospital-based nurses, case managers, and pharmacists. The final checklist was
      endorsed by the Society of Hospital Medicine. RESULTS: The finalized checklist is
      a comprehensive list of the processes and elements considered necessary for
      optimal patient handoff at hospital discharge. This checklist focused on
      medication safety, patient education, and follow-up plans. CONCLUSIONS: The
      development of content and process standards for discharge is the first step in
      improving the handoff of care from the inpatient to the posthospital setting.
      Refining this checklist for patients with specific diagnoses, in specific age
      categories, and with specific discharge destinations may further improve
      information transfer and ultimately affect patient outcomes.

PMID- 17219530
TI  - Moxibustion burns.

PMID- 17219531
TI  - Preparing for "diastole": advanced training opportunities for academic
      hospitalists.
AB  - Academic hospital medicine can be described as comprising periods of "systole,"
      during which hospitalists provide clinical care, and periods of "diastole," the
      portion of a hospitalist's time spent in nonclinical activities. Far from being a
      period of relaxation, diastole is an active component of a hospitalist's work,
      the time devoted to the pursuit of career advancement. This period is a critical
      opportunity for career development in terms of medical research, education,
      quality improvement, or administration. An appropriate balance of systole and
      diastole may potentially prevent burnout and allow hospitalists opportunities to
      focus on academic advancement. Although an increasing number of residency
      graduates opt for a career in academic hospital medicine, few are prepared for
      the period of diastole. This article describes several career options in academic
      hospital medicine, specifically, opportunities in education, research, quality
      improvement, and administrative opportunities. By informing future hospitalists
      about the career opportunities within academic hospital medicine possible through
      managing their diastolic time, we hope that future generations of trainees will
      be better prepared to enter this field.

PMID- 17219532
TI  - Rites of passage.

PMID- 17219533
TI  - Unfractionated- versus low-molecular-weight-heparin-associated HIT in
      hospitalized medical patients.

PMID- 17219535
TI  - Management of hyperglycemia.

PMID- 17219539
TI  - Pneumonia: 3 days of antibiotics for uncomplicated course.

PMID- 17219542
TI  - The core competencies in hospital medicine: a framework for curriculum
      development by the society of hospital medicine.

PMID- 17219569
TI  - Core competencies in hospital medicine: development and methodology.
AB  - BACKGROUND: The hospitalist model of inpatient care has been rapidly expanding
      over the last decade, with significant growth related to the quality and
      efficiency of care provision. This growth and development have stimulated a need
      to better define and characterize the field of hospital medicine. Training and
      developing curricula specific to hospital medicine are the next step in the
      evolution of the field. METHODS: The Core Competencies in Hospital Medicine: A
      Framework for Curriculum Development (the Core Competencies), by the Society of
      Hospital Medicine, introduces the expectations of hospitalists and provides an
      initial structural framework to guide medical educators in developing curricula
      that incorporate these competencies into the training and evaluation of students,
      clinicians-in-training, and practicing hospitalists. This article outlines the
      process that was undertaken to develop the Core Competencies, which included
      formation of a task force and editorial board, development of a topic list, the
      solicitation for and writing of chapters, and the execution of multiple reviews
      by the editorial board and both internal and external reviewers. RESULTS: This
      process culminated in the Core Competencies document, which is divided into three
      sections: Clinical Conditions, Procedures, and Healthcare Systems. The chapters
      in each section delineate the core knowledge, skills, and attitudes necessary for
      effective inpatient practice while also incorporating a systems organization and
      improvement approach to care coordination and optimization. CONCLUSIONS: These
      competencies should be a common reference and foundation for the creation of
      hospital medicine curricula and serve to standardize and improve inpatient
      training practices.

PMID- 17219599
TI  - Abstracts of the Society of Hospital Medicine annual meeting, May 4-5, 2006,
      Washington, DC, USA.

PMID- 17219574
TI  - How to use the core competencies in hospital medicine: a framework for curriculum
      development.
AB  - BACKGROUND: The seminal article that coined the term hospitalist, published in
      1996, attributed the role of the hospitalist to enhancing throughput and cost
      reduction, primarily through reduction in length of stay, accomplished by having
      a dedicated clinician on site in the hospital. Since that time the role of the
      hospitalist has evolved, and hospitalists are being called upon to demonstrate
      that they actually improve quality of care and the education of the next
      generation of physicians. A companion article in this issue describes in detail
      the rationale for the development of the Core Competencies document and the
      methods by which it was created. METHODS: Specific cases that hospitalists may
      encounter in their daily practice are used to illustrate how the Core
      Competencies can be applied to curriculum development. The cases illustrate 1) a
      specific problem and the need for improvement; 2) a needs assessment of the
      targeted learners (hospitalists and clinicians in training); 3) goals and
      specific measurable objectives; 4) educational strategies using the competencies
      to provide structure and guidance; 5) implementation (applying competencies to a
      variety of training opportunities and curricula); 6) evaluation and feedback; and
      7) remaining questions and the need for additional research. RESULTS: This
      article illustrates how to utilize The Core Competencies in Hospital Medicine to
      educate trainees and faculty, to prioritize educational scholarship and research
      strategies, and thus to improve the care of our patients. CONCLUSIONS: Medical
      educators should compare their learning objectives to the Core Competencies to
      ensure that their trainees have achieved competency to practice hospital medicine
      and improve the hospital setting.

PMID- 17219604
TI  - Spintronics: a challenge for materials science and solid-state chemistry.
AB  - Spintronics is a multidisciplinary field involving physics, chemistry, and
      engineering, and is a new research area for solid-state scientists. A variety of
      new materials must be found to satisfy different demands. The search for
      ferromagnetic semiconductors and stable half-metallic ferromagnets with Curie
      temperatures higher than room temperature remains a priority for solid-state
      chemistry. A general understanding of structure-property relationships is a
      necessary prerequisite for the design of new materials. In this Review, the most
      important developments in the field of spintronics are described from the point
      of view of materials science.

PMID- 17219607
TI  - Anti-HIV agents. Once-daily anti-HIV therapy in people co-infected with TB.

PMID- 17219606
TI  - Detection of Delta9-tetrahydrocannabinolic acid A in human urine and blood serum
      by LC-MS/MS.
AB  - Delta9-tetrahydrocannabinolic acid A (Delta9-THCA-A) is the precursor of Delta9
      tetrahydrocannabinol (Delta9-THC) in hemp plants. During smoking, the non
      psychoactive Delta9-THCA-A is converted to Delta9-THC, the main psychoactive
      component of marihuana and hashish. Although the decarboxylation of Delta9-THCA-A
      to Delta9-THC was assumed to be complete--which means that no Delta9-THCA-A
      should be detectable in urine and blood serum of cannabis consumers--we found
      Delta9-THCA-A in the urine and blood serum samples collected from police controls
      of drivers suspected for driving under the influence of drugs (DUID). For LC
      MS/MS analysis, urine and blood serum samples were prepared by solid-phase
      extraction. Analysis was performed with a phenylhexyl column using gradient
      elution with acetonitrile. For detection of Delta9-THCA-A, the mass spectrometer
      (MS) (SCIEX API 365 triple-quadrupole MS with TurboIonSpray source) was operated
      in the multiple reaction monitoring (MRM) mode using the following transitions:
      m/z357 --> 313, m/z357 --> 245 and m/z357 --> 191. Delta9-THCA-A could be
      detected in the urine and blood serum samples of several cannabis consumers in
      concentrations of up to 10.8 ng/ml in urine and 14.8 ng/ml in serum. The
      concentration of Delta9-THCA-A was below the Delta9-THC concentration in most
      serum samples, resulting in molar ratios of Delta9-THCA-A/Delta9-THC of
      approximately 5.0-18.6%. Only in one case, where a short elapsed time between the
      last intake and blood sampling is assumed, the molar ratio was 18.6% in the
      serum. This indicates differences in elimination kinetics, which need to be
      investigated in detail.

PMID- 17219608
TI  - Anti-HIV agents. Saquinavir--switching from Fortovase to Invirase.

PMID- 17219609
TI  - Anti-HIV agents. Saquinavir with fosamprenavir.

PMID- 17219610
TI  - Anti-HIV agents. Atazanavir and saquinavir.

PMID- 17219611
TI  - Report from the 4th International Workshop on Clinical Pharmacology of HIV
      Therapy. Efavirenz levels in the blood found higher in women.

PMID- 17219612
TI  - Report from the 4th International Workshop on Clinical Pharmacology of HIV
      Therapy. Monitoring levels of non-nukes considered important by some doctors.

PMID- 17219613
TI  - Report from the 4th International Workshop on Clinical Pharmacology of HIV
      Therapy. Atazanavir--booster of the future?

PMID- 17219614
TI  - Anti-HIV agents. How long will a first regimen last?

PMID- 17219615
TI  - Anti-HIV agents. Who gets abacavir allergies?

PMID- 17219616
TI  - Effect of daily repetitive transcranial magnetic stimulation on motor performance
      in Parkinson's disease.
AB  - Previous studies in patients with Parkinson's disease have reported that a single
      session of repetitive transcranial magnetic stimulation (rTMS) can improve some
      or all of the motor symptoms for 30 to 60 minutes. A recent study suggested that
      repeated sessions of rTMS lead to effects that can last for at least 1 month.
      Here we report data that both confirm and extend this work. Fifty-five
      unmedicated PD patients were classified into four groups: two groups (early and
      late PD) received 25 Hz rTMS bilaterally on the motor arm and leg areas; other
      groups acted as control for frequency (10 Hz) and for site of stimulation
      (occipital stimulation). All patients received six consecutive daily sessions
      (3,000 pulses for each session). The first two groups then received a further
      three booster sessions (3 consecutive days of rTMS) after 1, 2, and 3 months,
      while the third group had only one additional session after the first month.
      Unified Parkinson's Disease Rating Scale (UPDRS), walking time, key-tapping
      speed, and self-assessment scale were measured for each patient before and after
      each rTMS session and before and after the monthly sessions. Compared to
      occipital stimulation, 25 Hz rTMS over motor areas improved all measures in both
      early and late groups; the group that received 10 Hz rTMS improved more than the
      occipital group but less than the 25 Hz groups. The effect built up gradually
      during the sessions and was maintained for 1 month after, with a slight reduction
      in efficacy. Interestingly, the effect was restored and maintained for the next
      month by the booster sessions. We conclude that 25 Hz rTMS can lead to cumulative
      and long-lasting effects on motor performance.

PMID- 17219617
TI  - [External ear duplication, a rare branchial arch abnormality].

PMID- 17219618
TI  - Five-year data out on Viread.

PMID- 17219619
TI  - Fuzeon combination highly effective.

PMID- 17219620
TI  - Collaboration to develop MIV-170.

PMID- 17219621
TI  - Advisory issued for Epzicom.

PMID- 17219622
TI  - Recent publications in Hematological Oncology.

PMID- 17219623
TI  - Traveler's diarrhea: a 50-year perspective. Proceedings of a conference organized
      by the International Society of Travel Medicine. June 12-14, 2004. Jackson Hole,
      Wyoming, USA.

PMID- 17219624
TI  - Low-vision device.

PMID- 17219625
TI  - Actin structure in the outflow tract of normal and glaucomatous eyes.
AB  - To characterize the in situ distribution of actin in Schlemm's canal endothelium
      (SCE) and juxtacanalicular tissue (JCT) cells in glaucomatous human eyes, and
      compare to the distribution in normal eyes. Fresh human eye bank eyes were
      perfused and fixed at pressure (n=27 normal eyes and 22 confirmed glaucomatous
      eyes). Schlemm's canal was opened by microdissection and outflow tissues were
      labelled for confocal microscopy to visualize F-actin, nuclei, laminin and/or
      CD31. Images were acquired in Z-series from the inner wall of Schlemm's canal,
      juxtacanalicular tissue and outer corneoscleral meshwork. In normal eyes, inner
      wall Schlemm's canal endothelial (SCE) cells showed a dense peripheral F-actin
      band, as previously described. JCT cells showed a more random and amorphous F
      actin distribution. In glaucoma eyes, peripheral F-actin bands were less common
      in inner wall SCE cells; instead, F-actin was more centrally located within the
      cell and appeared "tangled". These actin tangles were also prominent in JCT cells
      of glaucoma eyes. Glaucoma eyes also demonstrated structures with features of
      cross-linked actin networks (CLANs), and more frequent occurrence of punctuate
      actin concentrations. There was a significant degree of heterogeneity, with some
      regions from glaucomatous eyes appearing normal and vice versa. F-actin
      architecture in human outflow pathway cells in situ differs between normal and
      glaucoma eyes, with glaucomatous tissue showing a more "disordered" actin
      architecture overall. Some of these changes are likely due to effects secondary
      to administration of anti-glaucoma medications. Most of the changes that we
      observed could potentially affect the biomechanical properties of the outflow
      pathway tissues in glaucoma, but their role in the pathogenesis of ocular
      hypertension remains unclear.

PMID- 17219626
TI  - The test of public scrutiny.

PMID- 17219627
TI  - Tuberculous intrathoracic lymphadenitis without paranchymal involvement:
      diagnostic challenges.

PMID- 17219628
TI  - [Top 100 hospitals: varying lists, varying reputations].

PMID- 17219630
TI  - Outreach. Active audience.

PMID- 17219631
TI  - Cancer survival improving. Treatments, early diagnosis key.

PMID- 17219632
TI  - Health tips. Lighten your holiday meal.

PMID- 17219633
TI  - Visualizing and treating the small intestine without surgery.

PMID- 17219634
TI  - Coenzyme Q10. Is it worth the expense?

PMID- 17219635
TI  - Persistent itching. A stubborn problem.

PMID- 17219636
TI  - How do I know when I should see a doctor for a sprained ankle? What's the unusual
      treatment?

PMID- 17219637
TI  - How you can aim for an ideal lifestyle. Take as many of these 5 steps as you can-
      simultaneously--to slash heart risks.

PMID- 17219638
TI  - Recipe for a heart-protective cake: hold the saturated fat.

PMID- 17219639
TI  - How to respond to cardiac arrest. 6 key steps you can take to save a life--even
      if you're untrained and alone.

PMID- 17219640
TI  - A new look at 3D heart imaging. A non-invasive way to reveal cardiac disease
      still errs, but is improving fast.

PMID- 17219641
TI  - Treat heart attack symptoms seriously. First heart attacks are often fatal in
      women. Here are 5 tips to tilt the odds in your favor.

PMID- 17219642
TI  - 5 easy ways to better heart health. Eating smart will reduce your cholesterol,
      blood sugar and risk of heart attack.

PMID- 17219643
TI  - Studies show aspirin affects women differently than men.

PMID- 17219644
TI  - Ever since I started menopause, my heart flutters from time to time. I t usually
      lasts several seconds. Is this normal?

PMID- 17219645
TI  - Should you get a CRP test to predict heart attack risks?

PMID- 17219646
TI  - Cracking the food label codes. For the sake of your heart, develop the fine art
      of reading the fine print.

PMID- 17219647
TI  - Go back to basics to avoid another bypass procedure.

PMID- 17219648
TI  - I recently went to the hospital with chest pains and was told that I hand't had a
      heart attack. Instead, my doctor said I had pericarditis. I'd like to hear from
      you about what that means and what the best treatment is.

PMID- 17219649
TI  - Infection fighters. LGV: an old infection resurges.

PMID- 17219650
TI  - Infection fighters. Key facts about LGV.

PMID- 17219651
TI  - Addictions. Crystal meth: understanding its allure.

PMID- 17219652
TI  - Addictions. Sex, lies and crystal.

PMID- 17219653
TI  - Anti-HIV agents. Coming soon: new protease inhibitors.

PMID- 17219654
TI  - Anti-HIV agents. TMC114--an overview.

PMID- 17219655
TI  - Anti-HIV agents. Interactions with TMC114.

PMID- 17219656
TI  - Anti-HIV agents. What the future holds for TMC114.

PMID- 17219657
TI  - Anti-HIV agents. Kaletra + atazanavir.

PMID- 17219658
TI  - Anti-HIV agents. Continuing or stopping 3TC.

PMID- 17219659
TI  - Anti-HIV agents. Abacavir once or twice daily.

PMID- 17219660
TI  - Anti-HIV agents. Needle-free T-20.

PMID- 17219662
TI  - Side effects. Using metabolomics for predicting side effects.

PMID- 17219661
TI  - Anti-HIV agents. Is FOTO a treatment interruption that works?

PMID- 17219663
TI  - Anti-HIV agents. Some American women don't reap a large benefit from HAART.

PMID- 17219664
TI  - Immune boosters. Italian study finds immune booster useful against genital warts.

PMID- 17219665
TI  - Anti-HIV agents. New and different drugs tested in people.

PMID- 17219666
TI  - Anti-HIV agents. Low rate of early virologic failure seen with a combination of
      Trizivir and tenofovir.

PMID- 17219667
TI  - Anti-HIV agents. Once-daily lopinavir/ritonavir (Kaletra).

PMID- 17219668
TI  - Complications & side effects. Supplements and CD4+ counts: study finds surprising
      results.

PMID- 17219669
TI  - Complications & side effects. Diabetes risk found higher for HAART users.

PMID- 17219670
TI  - Complications & side effects. Disappointing result for rosiglitazone and
      lipodystrophy.

PMID- 17219671
TI  - Nutrition and herbs. Tropical fruit juices and drug interactions.

PMID- 17219672
TI  - Nutrition and herbs. Researchers study marijuana users in Ontario.

PMID- 17219673
TI  - Nutrition and herbs. Cholesterol drug side effects may be linked to low nutrient
      levels.

PMID- 17219674
TI  - Cancer. Trends in cancer risk among women with HIV/AIDS.

PMID- 17219675
TI  - Cancer. Cancer risk in older people with HIV/AIDS.

PMID- 17219676
TI  - Co-infections. Hepatitis C virus linked to thyroid problems.

PMID- 17219677
TI  - Vaccines for HIV--looking to the future.

PMID- 17219678
TI  - Vaccines for HIV--Remune returns.

PMID- 17219679
TI  - Vaccines. Response to hepatitis A vaccine weak in some PHAs.

PMID- 17219680
TI  - Nutrition. Pilot study suggests high-dose niacin is safe and effective for some
      PHAs.

PMID- 17219681
TI  - Complications & side effects. Increase in blood clots found.

PMID- 17219682
TI  - Adherence. Harvard study finds adherence advice can sometimes backfire.

PMID- 17219683
TI  - Complications & side effects. Lipodystrophy: yesterday, today and tomorrow.

PMID- 17219684
TI  - Complications & side effects. Can TH9057 reduce fat deposits?

PMID- 17219685
TI  - Complications & side effects. Filling the face: some possible options.

PMID- 17219687
TI  - Complications & side effects. Cholesterol-lowering drugs and mitochondria.

PMID- 17219686
TI  - Complications & side effects. Clinical trial compares three face fillers.

PMID- 17219688
TI  - Complications & side effects. Do statins affect CD4+ cell counts?

PMID- 17219689
TI  - Complications & side effects. Can statins be used as anti-HIV drugs?

PMID- 17219690
TI  - Aspirin modified dendritic cells are potent inducers of allo-specific regulatory
      T-cells.
AB  - Salicylic acid (aspirin) is a widely used pharmacological agent with
      immunodmodulatory properties. Dendritic cells are key regulators of the immune
      response, and are capable of inducing hyporesponsiveness and regulatory activity
      in CD4+ T-cells. We have demonstrated that aspirin-treated dendritic cells are
      effective at antigen processing and presentation, and possess a unique potency
      for inducing regulatory activity in responder T-cells. Unlike immature dendritic
      cells, aspirin DCs are resistant to the effects of maturational stimuli, as
      determined by low levels of CD40, CD80, CD83 and CD86 expression. Aspirin DCs
      were demonstrated to express high levels of the co-inhibitor of T-cell activation
      ILT-3. Aspirin DCs themselves produce less IL-10 and more IL-12 than immature
      DCs, but no specific cytokine is necessary for their tolerogenic capacity. When
      naive CD4+ T-cells are exposed to aspirin DCs they produce significant levels of
      IFNgamma but these same T-cells are hypo-proliferative. Aspirin-treated DCs
      demonstrate the characteristics of a potential immunotherapy for controlling
      unwanted immune-responses such as the indirect pathway of allo-recognition that
      drives chronic allograft rejection.

PMID- 17219691
TI  - Tacrolimus in combination with FTY720--an analysis of renal and blood parameters.
AB  - Calcineurin inhibitors (CNIs) are routinely used in immunosuppressive therapy and
      both Cyclosporine (CsA) and Tacrolimus (FK506) show similar efficacies to prevent
      rejection and death within the first year after organ transplantation. However,
      their use is limited by side effects such as kidney damage, hypertension, onset
      of diabetes and hyperlipidemia. It is a consensus that compared with CsA, FK506
      causes less changes in blood pressures, serum lipids and renal function.
      Nevertheless, FK506 use is associated with a higher incidence of post-transplant
      diabetes mellitus (PTDM). FTY720 is a new compound that has shown a protective
      effect in animal models with respect to rejection in transplantation, ischemia
      reperfusion injury, autoimmune diseases and tumor development. FTY720 acts by
      altering lymphocytes homing from blood to peripheral lymphoid organs. In mice,
      FTY720 administered in combination with CsA during 21 days has prolonged skin
      allograft survival without causing significant renal changes. In a model of CsA
      induced chronic nephropathy in rats, FTY720 administration prevented renal injury
      suggesting benefit from using a combination of these drugs. In a canine kidney
      allograft model, FTY720 in combination with low doses of CsA or FK506 showed an
      addictive anti-rejection effect without causing critical adverse effects. We
      therefore, investigated whether 21 days of FTY720 administration in association
      with FK506 could prevent renal damage and development of diabetes in mice. Mice
      receiving FK506 alone or FTY720 + FK506 during 21 days showed changes in kidney
      function and structure besides an increase in blood glucose and lymphopenia. The
      FTY720 + FK506 combination requires further investigation with an aim toward
      understanding the mechanisms involved with respect to side effects.

PMID- 17219692
TI  - Heme oxygenase 1 and renal ischemia and reperfusion injury: the impact of
      immunosuppressive drug.
AB  - Ischemia and reperfusion injury (IRI) is the main etiology of acute renal failure
      in native and transplanted kidneys. In the transplantation field,
      immunosuppressive drugs may play an additional role in acute graft dysfunction.
      Acute cyclosporine nephrotoxicity (ATN) can result from vasoconstriction of the
      afferent arterioles, which may exacerbate deceased renal transplantation. HO-1 is
      a protective gene with anti-inflammatory and anti-apoptotic actions. We
      investigated whether HO-1 played a role in cyclosporine-induced renal dysfunction
      in an established model of IRI. METHODS: Cyclosporine (100 mg/kg) was
      administered to mice before being subjected to 45 min of ischemia. Blood and
      kidney samples were collected at 24, 48 and 120 h after surgery. Acute tubular
      necrosis and tubular regeneration were quantified. HO-1 gene transcripts were
      amplified by real-time PCR. RESULTS: Animals subjected to IRI presented with
      impaired renal function that peaked at 24 h (2.05 +/- 0.23 mg/dL), decreasing
      thereafter. Treatment with cyclosporine caused even more renal dysfunction at 48
      h, sustained up to 120 h after reperfusion (1.53 +/- 0.6 mg/dL), when compared to
      the controls (0.63 +/- 0.09 mg/dL, p < 0,05). Cyclosporine delayed tubular
      regeneration that was normally higher in controls at day 5 (67.0% vs. 37.6%, p <
      0.05). HO-1 was markedly up-regulated after IRI, and its expression was decreased
      by cyclosporine (2.06 folds). However, prior induction of HO-1 by cobalt
      protoporphyrin improved renal dysfunction. CONCLUSIONS: These results
      demonstrated that cyclosporine used in ischemic injured organs might also
      negatively affect post-transplantation recovery.

PMID- 17219693
TI  - Meeting of the immunization Strategic Advisory Group of Experts, November 2006-
      conclusions and recommendations.

PMID- 17219694
TI  - The present and future interface of technology and medical education.

PMID- 17219696
TI  - No ifs, ands, or butts: save the skin and stop the sore.

PMID- 17219697
TI  - Use of an atraumatic dressing in the treatment of a painful wound resulting from
      herpes zoster.

PMID- 17219698
TI  - Is a rose always a rose?

PMID- 17219699
TI  - A continence care champion for research. Interview by Barbara Zeiger.

PMID- 17219700
TI  - The use of botulinum toxin in the treatment of refractory overactive bladder.

PMID- 17219701
TI  - [The fertility of mines and the sexuality of stones in Greco-Roman antiquity].

PMID- 17219702
TI  - Horticultural classics.

PMID- 17219703
TI  - Proceedings, 104th Annual Meeting Medical Library Association, Inc., Washington,
      DC, May 21-26, 2004.

PMID- 17219704
TI  - [Life is short, art long: the proem of Seneca's De brevitate vitae].

PMID- 17219706
TI  - Findings of research misconduct.

PMID- 17219705
TI  - Acute fractures of the scaphoid.

PMID- 17219707
TI  - Nantes Actualite Transplantation 2006 Summary Report: innovative therapeutics in
      transplantation.

PMID- 17219708
TI  - The baby lab: how Elizabeth Spelke peers into the infant mind.

PMID- 17219709
TI  - The lunchroom rebellion: an haute-cuisine chef goes back to school.

PMID- 17219710
TI  - [The "Limophoros": Polybius III, 87, 2].
AB  - The word "limophoros", a hapax legomenon appearing in Polybius' Histories, does
      not mean scurvy, but rather scabies. Polybius created the word to describe an
      illness he believed was derived from a nutritional deficit, but can really only
      be seen as an attempt to describe an illness the etiology of which he was wholly
      unfamiliar.

PMID- 17219711
TI  - More underwater finds of Roman medical equipment.

PMID- 17219712
TI  - "Sede in tuo loco": a fourth-century uterine phylactery in Latin from Roman
      Britain.

PMID- 17219713
TI  - Sallust's Historiae, Dioskorides and the sites of the Korykos captured by P.
      Servilius Vatia.

PMID- 17219714
TI  - [From the library of Giovanni di Marco da Rimini, the Galen manuscript D XXV 2 in
      the Malatestiana Library in Cesena].

PMID- 17219715
TI  - [Galen's contribution to the medical method].

PMID- 17219716
TI  - Mesenchymal stem cells: characteristics and clinical applications.
AB  - Mesenchymal stem cells (MSCs) are bone marrow populating cells, different from
      hematopoietic stem cells, which possess an extensive proliferative potential and
      ability to differentiate into various cell types, including: osteocytes,
      adipocytes, chondrocytes, myocytes, cardiomyocytes and neurons. MSCs play a key
      role in the maintenance of bone marrow homeostasis and regulate the maturation of
      both hematopoietic and non-hematopoietic cells. The cells are characterized by
      the expression of numerous surface antigens, but none of them appears to be
      exclusively expressed on MSCs. Apart from bone marrow, MSCs are located in other
      tissues, like: adipose tissue, peripheral blood, cord blood, liver and fetal
      tissues. MSCs have been shown to be powerful tools in gene therapies, and can be
      effectively transduced with viral vectors containing a therapeutic gene, as well
      as with cDNA for specific proteins, expression of which is desired in a patient.
      Due to such characteristics, the number of clinical trials based on the use of
      MSCs increase. These cells have been successfully employed in graft versus host
      disease (GvHD) treatment, heart regeneration after infarct, cartilage and bone
      repair, skin wounds healing, neuronal regeneration and many others. Of special
      importance is their use in the treatment of osteogenesis imperfecta (OI), which
      appeared to be the only reasonable therapeutic strategy. MSCs seem to represent a
      future powerful tool in regenerative medicine, therefore they are particularly
      important in medical research.

PMID- 17219717
TI  - Protein 4.1, a component of the erythrocyte membrane skeleton and its related
      homologue proteins forming the protein 4.1/FERM superfamily.
AB  - The review is focused on the domain structure and function of protein 4.1, one of
      the proteins belonging to the membrane skeleton. The protein 4.1 of the red blood
      cells (4.1R) is a multifunctional protein that localizes to the membrane skeleton
      and stabilizes erythrocyte shape and membrane mechanical properties, such as
      deformability and stability, via lateral interactions with spectrin, actin,
      glycophorin C and protein p55. Protein 4.1 binding is modulated through the
      action of kinases and/or calmodulin-Ca2+. Non-erythroid cells express the 4.1R
      homologues: 4.1G (general type), 4.1B (brain type), and 4.1N (neuron type), and
      the whole group belongs to the protein 4.1 superfamily, which is characterized by
      the presence of a highly conserved FERM domain at the N-terminus of the molecule.
      Proteins 4.1R, 4.1G, 4.1N and 4.1B are encoded by different genes. Most of the
      4.1 superfamily proteins also contain an actin-binding domain. To date, more than
      40 members have been identified. They can be divided into five groups: protein
      4.1 molecules, ERM proteins, talin-related molecules, protein tyrosine
      phosphatase (PTPH) proteins and NBL4 proteins. We have focused our attention on
      the main, well known representatives of 4.1 superfamily and tried to choose the
      proteins which are close to 4.1R or which have distinct functions. 4.1 family
      proteins are not just linkers between the plasma membrane and membrane skeleton;
      they also play an important role in various processes. Some, such as focal
      adhesion kinase (FAK), non-receptor tyrosine kinase that localizes to focal
      adhesions in adherent cells, play the role in cell adhesion. The other members
      control or take part in tumor suppression, regulation of cell cycle progression,
      inhibition of cell proliferation, downstream signaling of the glutamate
      receptors, and establishment of cell polarity; some are also involved in cell
      proliferation, cell motility, and/or cell-to-cell communication.

PMID- 17219718
TI  - Expression of insulin-like growth factor-I (IGF-I) in alveolar macrophages and
      lymphocytes obtained by bronchoalveolar lavage (BAL) in interstitial lung
      diseases (ILD). Assessment of IGF-I as a potential local mitogen and
      antiapoptotic cytokine.
AB  - Little is known about IGF-I expression in the alveolar lymphocytes (AL), and
      about local role of IGF-I in physiological conditions and in interstitial lung
      diseases. Bronchoalveolar lavage was carried out in patients with silicosis,
      asbestosis, idiopathic pulmonary fibrosis (IPF) and sarcoidosis, as well as in
      control subjects (n = 13, 9, 12, 56, 15, resp). Alveolar macrophages (AM) and
      lymphocytes (AL) were studied for (1) IGF-I, BCL-2, Fas and Fas Ligand expression
      and (2) cell cycle (incl. sub-G1 peak of late apoptosis) with propidium iodide
      (PI). Flow cytometry (FC) and immunocytochemistry were used. AL early apoptosis
      was detected by Annexin V FITC/PI staining. IGF-I was present in AL of all tested
      groups. The number of IGF-I positive AL was significantly higher in IPF (52 +/-
      6.7%) and in later (II and III) stages of sarcoidosis (39 +/- 7.8 vs 16 +/- 4.0%
      in controls, p < 0.05). Increased BCL-2 expression in AL was detected in IPF and
      sarcoidosis. In all tested groups, AL were almost exclusively Fas+ T cells.
      Generally, a low number of AL entered apoptosis; no significant differences were
      found between patient groups, except decreased apoptosis rate in sarcoidosis
      (0.60 +/- 0.17 vs 1.15 +/- 0.33% in controls, p < 0.05). Proportion of AL
      positive for IGF-I was significantly correlated with parameters reflecting AL and
      AM cell proliferation and BCL-2 expression (e.g. AL IGF-I+ vs AM in S phase of
      cell cycle: r(S) = +0.50, p = 0.001), but not with apoptosis. The results show
      that human alveolar lymphocytes express IGF-I in normal conditions, as well as in
      ILD. The proportion of IGF-I+ lymphocytes was significantly increased in IPF and
      at later stages of sarcoidosis. In our material there was no evidence for
      profibrogenic or antiapoptotic activity of IGF-I. We suggest that IGF-I
      originating from AL may be locally active as a mitogen for alveolar macrophages
      and lymphocytes in ILD.

PMID- 17219719
TI  - Effect of Trichostatin A on CD4 surface density in peripheral blood T cells.
AB  - Acetylation level of chromatin histones is maintained by histone acetylases
      (HATs) and deacetylases (HDACs) and correlates with transcriptional activity of
      genes. Trichostatin A (TSA) is HDAC inhibitor that causes various effects in
      cells, including immunomodulation. The CD4 antigen is a key coreceptor involved
      in activation of T helper cells. Using quantitative real-time PCR (RQ-PCR) and
      flow cytometry techniques, we estimated CD4 transcript level and density of CD4
      antigen on the surface of TSA-treated stimulated and unstimulated peripheral T
      cells. We observed a dose dependent decrease in CD4 mRNA level and antigen
      density on surface of TSA-treated stimulated T cells. However, we did not observe
      any significant TSA effect on CD4 mRNA and protein expression in unstimulated T
      cells. Our data suggest that TSA may induce biosynthesis of factors responsible
      for negative regulation of CD4 antigen expression in stimulated T cells. Our
      investigation may support previous observation that this drug has
      immunosuppresive effect on primary T cells and may be useful in treatment of
      certain autoimmune disorders.

PMID- 17219720
TI  - Expression of the membrane complement regulatory proteins (CD55 and CD59) in
      human thymus.
AB  - CD59 is one of the key molecules involved in cell protection against autologus
      complement. The fact that complement regulatory proteins are able to prevent
      hyperacute rejection of organs in pig to primate model, raises the question of
      possible complement regulatory protein (CRP) involvement in the maturation of
      immunological system. We report here that in foetal and postnatal human thymus,
      CD59 and CD55 are primarily located on Hassall's corpuscles and medullary
      epithelial cells. This localization highly correlates with the expression of
      CD30L, which is the member of the tumour necrosis factor superfamily.
      Additionally, TUNEL technique was used to visualize distribution of apoptotic
      cells in the thymus, which revealed the presence of apoptotic cells closely
      associated with the Hassall's corpuscles. The observed co-localization of CD59,
      CD55 and CD30L might suggest an involvement of the complement system in thymic
      selection in humans.

PMID- 17219721
TI  - Immunohistochemical localization of proliferating cell nuclear antigen (PCNA) in
      the pig ovary.
AB  - The aim of the study was to determine the expression of proliferating cell
      nuclear antigen protein (PCNA) in the pig ovary. The localization of PCNA was
      demonstrated in paraffin sections of pig ovarian tissue using primary mouse
      monoclonal anti-PCNA antibody. In primordial follicles, no remarkable staining
      for PCNA either in granulosa cells or in the oocytes was observed. In primary to
      secondary follicles, positive staining in oocytes and in some granulosa cells was
      detected. The advanced preantral and particularly actively growing small to large
      antral follicles showed extensive PCNA labeling in the layers of granulosa and
      theca cells and in the cumulus cells encircling the oocyte. PCNA labeling was
      expressed in nuclei of oocytes in preantral and small antral follicles. In
      atretic follicles, the level of PCNA protein expression was dependent on the
      stage of atresia. Follicles demonstrating advanced atresia showed only limited or
      no PCNA labeled granulosa and theca cells. The results of the study demonstrate
      that follicular growth and development in pig ovary may be effectively monitored
      by determining the granulosa cell expression of PCNA.

PMID- 17219722
TI  - Riboflavin content in autofluorescent earthworm coelomocytes is species-specific.
AB  - We have recently shown that a large proproportion of earthworm coelomocytes
      exhibit strong autofluorescence in some species (Dendrobaena veneta,
      Allolobophora chlorotica, Dendrodrilus rubidus, Eisenia fetida, and Octolasion
      spp.), while autofluorescent coelomocytes are very scarce in representatives of
      Lumbricus spp. and Aporrectodea spp. Riboflavin (vitamin B2) was identified as a
      major fluorophore in Eisenia jetida coelomocytes. The main aim of the present
      experiments was to quantify riboflavin content in autofluorescent coelomocytes
      (eleocytes) from several earthworm species through a combination of flow
      cytometric and spectrofluorometric measurements. Spectrofluorometry of
      coelomocyte lysates showed that riboflavin was non-detectable in the coelomocytes
      of Aporrectodea spp. and Lumbricus spp., but was a prominent constituent of
      lysates from species with autofluorescent eleocytes. In the latter case,
      riboflavin content was the highest in E. fetida, followed by Octolasion spp. > A.
      chlorotica > D. rubidus. The riboflavin content of coelomocytes correlates
      positively with eleocyte autofluorescence intensity measured by flow cytometry
      and visible with fluorescence microscopy.

PMID- 17219723
TI  - Symptom occurrence, symptom distress, and quality of life in renal transplant
      recipients.
AB  - The growing number of persons who have successful renal transplants and the
      challenges they undergo as they adjust to changed lifestyles increases the need
      for knowledge of the recipient's view of the changes resulting from the
      transplantation process. One area for exploration is the recipient's perception
      of the symptoms that occur after transplantation. The purpose of this study was
      to determine symptom occurrence and symptom distress following renal
      transplantation and their relationships to quality of life in patients with renal
      transplants.

PMID- 17219724
TI  - A preceptor training program model for the hemodialysis setting.
AB  - The implementation of a preceptor training program is an integral step to
      improving the education of nurses entering the specialty of nephrology nursing.
      This preceptor training model integrates the components of the preceptor,
      orientee, educational support, administrative support, and incentives to form a
      basis for an effective preceptor program model This model was piloted in a group
      of outpatient dialysis facilities. Benefits were achieved from the program,
      including nursing growth, leadership development, and anticipated improved nurse
      recruitment and retention.

PMID- 17219725
TI  - Narrative literature review: sexual dysfunction in the patient on hemodialysis.
AB  - Sexual dysfunction is common in patients on hemodialysis. This narrative
      literature review utilized Roy's Adaptation Model to identify sexual dysfunction
      and its effect on adaptive modes in patients on hemodialysis. The majority of
      studies reviewed indicated a physiologic effect in men (78%). Fewer studies
      reported an effect on self-concept (66%), intimate relationship (21%), or
      family/social roles (less than 1%). Findings also revealed minimal patient
      expression of sexual dysfunction to health care providers.

PMID- 17219727
TI  - Erythropoietin claims monitoring policy: implications of the October 2006 update
      continuing.
AB  - The Centers for Medicare and Medicaid Services issued a revised erythropoietin
      claims monitoring policy that governs reimbursement for Epoetin alfa and
      darbepoetin alfa in patients on dialysis effective October 1, 2006. The new
      policy reinforces the upper Hb target level of 12.0 g/dL. However, the new
      provisions also allow increased latitude for making timely dose adjustments in
      response to the variability in Hb levels that occurs due to changes in patient
      status.

PMID- 17219729
TI  - Using normalized protein nitrogen appearance (nPNA) in assessing nutrition.

PMID- 17219728
TI  - Chronic kidney disease and cardiovascular disease--using the ANNA Standards and
      Practice Guidelines to improve care. Part 1: the epidemiology of chronic kidney
      disease: the risk factors and complications that contribute to cardiovascular
      disease.
AB  - Recent National Kidney Foundation Kidney Disease Outcome Quality Initiative
      Guidelines for cardiovascular disease recommend that patients with chronic kidney
      disease be considered at highest risk for development of cardiovascular disease
      and that cardiac risk factor reduction begin with diagnosis of chronic kidney
      disease. Risk factors for cardiovascular disease in patients with chronic kidney
      disease include both traditional and nontraditional renal-related cardiac risk
      factors. The ANNA Nephrology Nursing Standards of Practice and Guidelines for
      Care can provide the foundation for planning care to patients with CKD and not
      only slow the progression of CKD but reduce exposure to cardiac risk factors.
      This article, on the epidemiology of chronic kidney disease and the risk factors
      and complications that contribute to cardiovascular disease, is the first in a
      series of three articles on the risk factors and complications related to chronic
      kidney disease and its impact on cardiovascular disease.

PMID- 17219730
TI  - The "cushion cannulation" technique.

PMID- 17219731
TI  - Is the burden worth the benefit of the Doctorate of Nursing (DNP) for NPs? Doctor
      of Nursing Practice: the time is now.

PMID- 17219732
TI  - Online mentoring: ANNAConnections.
AB  - As the number of patients with chronic kidney disease (CKD) rises exponentially,
      there is an increased demand for nephrology nurses with expertise in all areas of
      practice. At this time of a serious nursing shortage, professional associations
      are needful of members able to assume leadership positions and prepare the
      organizations for the future. Novices to nursing, to nephrology or to leadership
      present a challenge to all areas of practice, from CKD clinics to dialysis units
      to transplant units, and to the maintenance and growth of professional
      associations. The purpose of this article is to introduce an innovative mentoring
      program that allows facilitation of the growth and development of nephrology
      nurses from novice to expert in multiple areas of career or leadership
      development.

PMID- 17219733
TI  - Novel drug resistance mutations in HIV: recognition and clinical relevance.
AB  - During its spread among humans, HIV-1 has developed an extraordinary degree of
      genetic diversity. The pol region encoding for viral enzymes such as the reverse
      transcriptase and the protease, and the env region encoding for the viral
      glycoprotein gp41 are subjected not only to natural variation, but also to the
      selection pressure imposed by the pharmacologic treatment. Under these conditions
      in HIV-1 infected people, the virus is able to escape from antiviral drugs by
      accumulating mutations, either alone or in clusters. The patterns of mutations
      accumulated by HIV-1 under drug pressure are quite variable, depending on the
      backbone of virus strains, the level and type of pharmacologic pressure, and the
      length of therapy. To date, a high number of mutations in protease, reverse
      transcriptase, and gp41 have been associated with reduced susceptibility to the
      antiretroviral drugs currently available. However, a number of studies
      continuously highlight the existence of additional mutations beyond those
      currently known to be involved in the development of drug resistance in vivo.
      Most of these so-called "novel" mutations are involved in agonistic correlations
      with the classical drug resistance mutations on divergent evolutionary pathways,
      and are associated with an increased resistance to specific drugs. At the same
      time, the presence of some novel mutations at therapeutic failure has also been
      significantly associated with an increase of viremia, thus suggesting that they
      may also play a compensatory role leading to improved viral replication.
      Interestingly, some natural polymorphisms in drug-naive patients have been
      significantly associated with the development of drug resistance mutations at
      failure, thus suggesting their ability to decrease the genetic barrier to the
      development of drug resistance. In contrast, other novel mutations are negatively
      associated with specific antiviral treatment, showing negative interactions with
      relevant drug resistance mutations, and are associated with increased
      susceptibility to specific drugs. This article reviews the importance of
      recognition and the clinical relevance of novel mutations involved in resistance
      to the currently used antiretroviral drugs, discussing in particular the role of
      novel drug resistance mutations in the reverse transcriptase enzyme. Such novel
      mutations should be considered for improved prediction of clinical response to
      antiretroviral drugs and for assessing the efficacy of next-generation drugs.

PMID- 17219734
TI  - Switching strategies to improve lipid profile and morphologic changes.
AB  - Metabolic alterations and body fat changes are well-recognized limitations of
      protease inhibitor-based regimens. Strategies of replacing protease inhibitors
      with nonnucleoside reverse transcriptase inhibitors or abacavir have been shown
      to improve metabolic abnormalities, particularly by decreasing cholesterol and
      triglyceride levels, and reducing cardiovascular risk. The various therapeutic
      options show differences in efficacy, tolerability, and metabolic outcomes.
      Abacavir seems to be better tolerated, at least in the only randomized trial in
      which the three options were compared face-to-face, but it is associated with
      higher virologic failure in patients with prior suboptimal nucleoside therapy.
      Nonnucleoside reverse transcriptase inhibitors, particularly nevirapine, result
      in a better lipid profile with a greater increase in HDL cholesterol and in the
      HDUtotal cholesterol ratio, one of the most important parameters associated with
      a reduction in cardiovascular risk. Efavirenz has been associated with increased
      triglyceride levels in some studies. Although protease inhibitor compounds as a
      family have been linked to metabolic and body fat alterations, new drugs such as
      atazanavir seem to be associated with a more favorable lipid profile. Lipoatrophy
      is a stigmatizing complication in HIV-infected patients receiving HAART. There is
      strong evidence suggesting a prominent role of thymidine analogs, mainly
      stavudine, in its development. Substitution of stavudine or zidovudine for
      abacavir or tenofovir partially improves peripheral fat loss. In addition, the
      lipid profile significantly improves. Finally, although the extended use of non
      thymidine nucleoside analogs and the development of new families of
      antiretroviral drugs will probably result in a lower impact in lipids and
      morphologic changes, many patients are currently under treatment with these
      compounds. In this setting, switching strategies may be useful to minimize
      clinical and psychological consequences, improving the quality of life of HIV
      infected patients treated with HAART.

PMID- 17219735
TI  - Atherosclerosis in HIV patients: a new face for an old disease?
AB  - As we have become more familiar with the pathogenesis of atheroma, it has become
      recognized atherogenesis is mainly an inflammatory disease. Therefore, it is not
      surprising that a body of evidence demonstrates that endothelium injury is
      associated with the progression and severity of HIV infection. Another important
      question is: do antiretroviral drugs increase or reduce endothelial injury?
      Various studies support the hypothesis that HAART does induce activation of
      endothelial function. Thus, HIV virus as well as immune reconstitution and HAART
      itself promote premature endothelial activation. Such a prominent role played by
      inflammatory events could affect the structure of the arterial lesions in HIV
      patients that could present different characteristics with respect to the
      classical atheroma. In fact, in two HIV patients with severe stenosis of the
      carotid, histology revealed extensive inflammatory infiltration of the vascular
      wall. The characteristics of these lesions were similar to those of arteritis.
      Another study evidenced that the ultrasonographic structure of the lesions in HIV
      patients substantially differ from those found in atherosclerosis, sharing
      similar characteristics with arteritis. We hypothesize that the atherosclerotic
      lesions in HIV patients develop in two distinct phases: the first one
      characterized by an inflammation of the vascular wall, and subsequently, the
      lesions could evolve towards the classic feature of the atheroma. The lesions in
      the first phase are probably determined by immunodeficiency, immune
      reconstitution, and the same effect of HAART. In the second phase they could be
      maintained by the classic risk factors.

PMID- 17219736
TI  - Clinical implications of HIV drug resistance to nucleoside and nucleotide reverse
      transcriptase inhibitors.
AB  - This review focuses on issues pertinent to the epidemiology and clinical
      interpretation of resistance to nucleos(t)ide reverse transcriptase inhibitors.
      Nucleoside reverse transcriptase inhibitor resistance mutations, and especially
      thymidine analog mutations, remain the most common form of resistance detected in
      drug-naive patients. At the same time, improved treatment strategies, changes in
      prescribing policies, and prompt management of treatment failure are changing the
      prevalence and patterns of nucleoside reverse transcriptase inhibitor resistance
      in treatment-experienced patients. The clinical interpretation of nucleoside
      reverse transcriptase inhibitor resistance is being increasingly refined, helped
      by improved understanding of resistance pathways, development of sophisticated
      methods of analysis of genotypic resistance patterns, and introduction of
      clinically relevant cutoffs. Correlation of genotypic and phenotypic resistance
      data to clinical outcomes is essential to allow appropriate interpretation. In
      some cases, phenotypic data, either obtained directly by phenotypic tests or
      extrapolated from genotypic results, provide the most immediate predictors of
      virologic response. In other cases, genotypic analyses identify mutations that
      impact on responses without showing a marked effect on the phenotype, by either
      acting as "sentinel" markers for the presence of resistance undetectable by
      standard methods, or by lowering the genetic barrier to the evolution of
      resistance. The potential benefits of nucleoside reverse transcriptase inhibitor
      resistance, through hypersusceptibility and fitness effects, are also
      increasingly understood and exploited in clinical practice. Although progress has
      been significant, there remain many challenges. It is often questioned whether
      genotypic scores and clinical cutoffs obtained by various methods and from
      frequently small datasets can be reliably extrapolated to the general population
      of treated patients. At the same time, there is a need to define the role of
      reverse transcriptase mutations that are identified by statistical analyses as
      being associated with nucleoside reverse transcriptase inhibitor exposure, but
      have unknown effects on virus phenotype and clinical outcome. Novel mechanisms
      have also been proposed to play a role in nucleoside reverse transcriptase
      inhibitor resistance, including changes in RNaseH that are not targeted by
      routine testing at present. One additional, currently unresolved issue is the
      clinical relevance of minority resistant species and the feasibility of
      introducing ultra-sensitive resistance tests in routine diagnostic settings. The
      most appropriate viral-load cutoff for performing resistance tests and the
      reliability of results obtained at low copy numbers are similarly controversial.
      In spite of these limitations, resistance testing with appropriate interpretation
      provides an important guide to successful treatment outcomes and necessary
      support to the introduction of new treatment strategies.

PMID- 17219737
TI  - Mechanisms of CD4 T-cell depletion triggered by HIV-1 viral proteins.
AB  - Infection with HIV-1 leads to progressive CD4 T-cell death, resulting in AIDS
      development. The mechanisms that trigger this CD4 T-cell death are still not
      fully understood, but a lot of data indicates that apoptosis plays a major role
      in this cell demise. Both infected and uninfected CD4 T-cells can die during HIV
      1 infection by different cell-death pathways, but HIV-1-induced, bystander, CD4 T
      cell killing is now recognized as central to immunodeficiency. The HIV-1 directly
      modulates CD4 T-cell death using multiple different strategies in which several
      viral proteins have an essential role. Recent data demonstrate that relationships
      can exist between the three main types of programmed cell death, i.e. apoptosis,
      autophagic programmed cell death, and necrosis-like programmed cell death. Almost
      nothing is currently known about the role of necrosis-like programmed cell death
      in CD4 T-cell death induced by the viral proteins, but a very recent study
      demonstrates that autophagy is needed to trigger apoptosis of bystander CD4 T
      cells, further increasing the level of complexity of this pathology. This review
      presents an overview of the major types of programmed cell death and details the
      mechanisms by which the HIV-1 viral proteins control both infected and uninfected
      CD4 T-cell death.

PMID- 17219738
TI  - Nevirapine-associated hepatotoxicity in virologically suppressed patients--role
      of gender and CD4+ cell counts.

PMID- 17219739
TI  - The problems with histopathological verification of breast microcalcification
      clusters in the stereotactic mammotome biopsy specimens.
AB  - The aim of the study was analysis of the cases, where histopathological
      examination failed to confirm the presence of breast microcalcifications in the
      SMB (stereotactic mammotome biopsy) specimens. Between 2000-2004, 242 patients
      underwent SMB under the guidance of digital mammography to verify breast
      microcalcification clusters of BI-RADS (Breast Imaging Reporting and Data System)
      3-5 categories. In 39 of these patients histopathological examination did not
      confirm microcalcifications despite visualization on the radiograms. All such
      cases were additionally evaluated under polarized light microscope to detect
      microcalcifications containing birefringent calcium oxalate deposits. In all 39
      patients only benign breast abnormalities were detected. In none of these cases
      breast microcalcifications were revealed in the additional evaluation under
      polarized light microscope. In some cases histopathological examination of the
      SMB specimens of breast microcalcifications may not confirm their presence
      despite visualization on the radiograms. The bioptates sent for the examination
      should he placed in the order of sampling at the same level and in such form
      embedded in the paraffin blocks. Radiograms confirming the location of
      microcalcifications should accompany the specimens. If standard assessment does
      not demonstrate microcalcifications, serial cutting and additional evaluation
      under polarized light microscope are recommended.

PMID- 17219740
TI  - MMAC/PTEN gene expression in endometrial cancer: RT-PCR studies.
AB  - Mutations in the MMAC/PTEN (phosphatase and tensin homologue deleted on
      chromosome 10) gene are documented in cancers of the breast, prostate, ovary,
      colon, melanoma, glioblastoma, lymphoma and endometrium. In the present work
      MMAC/PTEN gene expression in women with endometrial adenocarcinoma (n=70) in RNA
      samples obtained from cancer tissue were investigated. Control DNA was obtained
      from 68 normal endometrial tissue. The MMAC/PTEN expression was determined by RT
      PCR analysis. The expression of MMAC/PTEN gene in endometrial adenocarcinoma
      cases was significantly reduced compared to the expression in the normal samples
      (P < 0.05). Furthermore the significant difference (P < 0.05) was observed
      between the expression of MMAC/PTEN in stage III versus lower stages of
      endometrial cancer. The results support the hypothesis that the MMAC/PTEN gene
      expression may be associated with the incidence of endometrial cancer.

PMID- 17219741
TI  - Immunophenotype of sporadic and familial adenomatous polyposis associated fundic
      gland polyps: a mucin and MIB1 study.
AB  - BACKGROUND: Fundic Gland Polyps (FGPs) are small sessile (2-5 mm) usually
      multiple polyps arising in the gastric, acid-secreting mucosa, described both in
      a sporadic form, prevalently in middle aged females, and associated with familial
      adenomatosis coli (FAP)-Gardner's syndrome and their attenuated variants
      (syndromic form). AIMS: We performed an immunohistochemical study on 5 syndromic
      (4 cases without and 1 case with dysplasia) and 28 sporadic FGPs, using
      monoclonal antibodies (MoAbs) against normal epitopes of fundic mucosa (Ck20, the
      surface gastric mucin M1, EMA, ChA), H. pylori and HLA-DR(Ia) antigens, CEA and
      mucin epitopes, and the Ki67 (MIB1) proliferation antigen, in order to establish
      the immunophenotype of FGPs; find any possible differences between sporadic and
      syndromic polyps. RESULTS: Ck20 and M1 were positive on surface and foveolar
      epithelium of controls, whereas sporadic and syndromic FGPs showed an enhanced
      deep positivity below foveolar necks ("foveolar metaplasia"); EMA was strongly
      positive on parietal cells, highlighting intracytoplasmic canaliculi.
      Chromogranin-positive cells in FGPs were alike controls, except for a sporadic
      case with micronodular hyperplasia. Ck7, as expected, was negative in controls,
      whereas the 5 syndromic FGPs and 25 of 28 sporadic FGPs showed a diffuse
      superficial and deep expression. H. pylori anti-serum gave negative results on
      all cases, and only 3 sporadic FGPs showed epithelial expression of HLA-DR(Ia).
      Syndromic FGPs were CEA negative, whereas 32% of sporadic FGPs expressed it. FGPs
      showed a neoexpression of the mucin oncofetal epitopes syalil-Tn (3/5 syndromic,
      82% sporadic) CA19.9 and CA50 (4/5 syndromic, 14% sporadic). MIB1-labelling index
      of surface (30.5%) and deep (37.1%) compartments of the 4 syndromic FGPs without
      dysplasia was enhanced, with high statistical significance (p < 0.0001) both in
      comparison to controls (16.9% superficial stain only) and sporadic FGPs (15.8%
      surface, 19.5% deep labeling indexes). Moreover, the MIB1 labeling-index of the
      syndromic case with dysplasia (60.8% surface, 56.6% deep labeling indexes) was
      further enhanced in comparison with the other 2 syndromic cases. CONCLUSIONS:
      Sporadic and syndromic FGPs showed a neoexpression of Ck7, CEA, and mucin
      epitopes. As these markers are normal antigens of fetal stomach, FGPs showed a
      fetal, "immature" immunophenotype. The only difference we found between syndromic
      and sporadic polyps was a statistically significant enhanced MIB1-labelling index
      expression by syndromic FGPs, further enhanced in the syndromic FGP with
      dysplasia.

PMID- 17219742
TI  - Immunohistochemical expression of bcl-2 in UICC stage I and III colorectal
      carcinoma patients: correlation with c-erbB-2, p53, ki-67, CD44, laminin and
      collagen IV in evaluating prognostic significance.
AB  - BACKGROUND: The objective of this study was to evaluate the expression of bcl-2
      in UICC stage I and stage III (Dukes's stage B and C) colorectal adenocarcinoma
      and to examine its association with clinicopathological features, c-erbB-2, p53,
      ki-67, CD44, laminin and collagen IV and long term outcome. METHODS: Paraffin
      embedded specimens from 61 patients with UICC stage I (Dukes's stage B) and 39
      patients with UICC stage III (Dukes's stage C) colorectal adenocarcinoma who were
      treated with surgery were assessed. We determined by immunohistochemistry the
      expression of bcl-2, c-erB-2, p53, ki-67, CD44, laminin and collagen IV with 5
      year follow up. RESULTS: Cytoplasmic staining of the bcl-2 gene product was seen
      in the tumour cells of 27 cases (27%). Expression of bcl-2 protein was unrelated
      to patient sex, age, tumour site or tumour grade, but was related to tumour stage
      (p = 0.012). No significant association was demonstrated between bcl-2 and c-erbB
      2, p53 or CD44. However, there was very strong evidence of correlation between
      bcl-2 staining and ki-67, laminin and collagen IV. There was a trend towards
      increased survival in patients whose tumours expressed bcl-2 protein. When a
      correlation between bcl-2 and the other markers had been made the positive
      expression of bcl-2 was beneficial. CONCLUSIONS: The results from this study
      would suggest that expression of bcl-2 appear to be useful in selecting a group
      of colorectal cancer patients with a better prognosis.

PMID- 17219743
TI  - Metastases to the breast from extramammary malignancies: a clinicopathologic
      study of 12 cases.
AB  - Along with a brief review of the literature, we report the clinicopathologic
      features of 12 cases of extramammary malignancies metastatic to the breast.
      Histological diagnoses of the primary tumor were as follows: non-Hodgkin diffuse
      large B-cell lymphoma (3 patients), acute mycloid leukemia (3 patients), serous
      papillary adenocarcinoma, well-differentiated adenocarcinoma, squamous cell
      carcinoma, undifferentiated neoplasm, mesothelioma, and melanoma. The most common
      mammographic finding was a well-circumscribed mass with increased density but
      without speculation, calcifications or other signs that characterize the majority
      of primary carcinomas. Ultrasound revealed well-circumscribed masses without
      retrotumor acoustic shadowing. The interval between diagnosis of primary cancer
      and the appearance of breast metastasis ranged from 0 to 108 months (mean: 17,
      median: 1). Survival after the detection of the breast metastases ranged from 0.2
      to 144 months (mean: 23, median: 9.5). In conclusion, metastasis can mimic either
      benign disease or primary malignancy and is often an unexpected diagnosis in a
      patient presenting with a breast mass. Thus, an accurate diagnosis is important
      to avoid unnecessary mutilating surgery. These masses generally indicate
      disseminated metastatic disease, with a very poor survival rate.

PMID- 17219744
TI  - Choriocarcinoma within the third trimester placenta--a case report.
AB  - A small focus of choriocarcinoma has been incidentally found within an otherwise
      normal, third trimester placenta which was sent to the pathomorphological
      examination because of the stillbirth of the child at 31st week of gestation. The
      autopsy of the child was not performed. Macroscopically focus of choriocarcinoma
      has looked as a small infarct and was indistinguishable from the second lesion,
      which was microscopically confirmed to be a real infarct. beta-hCG level was
      increased at the time of delivery, but come back to normal very quickly. There
      were no metastases in the mother at the time of delivery and the follow-up did
      not show any evidence of metastatic disease either.

PMID- 17219745
TI  - Liposarcoma of the uterine corpus coexisting with preinvasive cervical cancer--a
      case report.
AB  - Case report of isolated liposarcoma of the uterine corpus coexisting with
      preinvasive cervix cancer in 71-year-old woman, who 41 years ago underwent the
      enucleation of the uterine corpus myomas. In tumor histogenesis the malignant
      transformation of fat cells, which might have been previously transferred to
      myometrium, was taken into consideration. The 8 year long follow-up revealed
      neither recurrence nor metastases.

PMID- 17219746
TI  - Women and suicidal behavior.

PMID- 17219747
TI  - Monitoring deliberate self-harm presentations to general hospitals.
AB  - Monitoring of deliberate self-harm (DSH) presentations to hospitals (and in other
      settings) is receiving increased attention in many countries. This is due to
      greater recognition of the size of the problem and awareness of its relevance to
      suicide prevention policy initiatives, because of the strong association between
      DSH and suicide. A system for monitoring all DSH presentations has been in place
      in the general hospital in Oxford for 30 years. Based on our experience, in this
      paper we describe procedures for monitoring, including case definition and
      identification, linkage of persons and episodes in order to investigate
      repetition of DSH and other outcomes (including deaths), and data protection and
      ethical issues. We also provide details of how to carry out monitoring, including
      different models of data collection, and what data to collect. Finally we
      consider the potential uses of the data for both clinical and research purposes,
      including evaluation of national suicide prevention initiatives.

PMID- 17219748
TI  - Personality and repeated suicide attempts in dependent adolescents and young
      adults.
AB  - This study compared personality characteristics of subjects with dependence
      disorders who had previously made a suicide attempt. The population, recruited in
      France, Belgium, and Switzerland, was composed of 570 subjects (225 females, 345
      males, mean age = 27.3, SD = 8.5). The subjects' psychological dimensions were
      investigated by means of several self-report questionnaires including: BDI-13
      (Beck), Sensation-Seeking Scale (Zuckerman), Toronto Alexithymia Scale (Taylor),
      Interpersonal Dependency Inventory (Hirschfeld), MMPI-2, and some additional
      scales. For most dimensions, repeat attempters, both past and recent, but more
      specifically the recent repeaters, had a more severe psychological profile
      compared to the other suicide attempters.

PMID- 17219749
TI  - Reaching suicidal people with media campaigns: new challenges for a new century.
AB  - Five variables were investigated in the evaluation of Suicide Prevention Weeks
      (SPW) held in 1999, 2000, and 2001 in Quebec, Canada: exposure to the campaign,
      previous suicide ideation, knowledge, attitudes, and intentions. After the year
      2000 campaign, a telephone survey conducted on a representative sample of 1020
      men revealed that only those actually exposed to the SPW had gained more
      knowledge of suicide facts and resources. However, the SPW did not influence
      attitudes or intentions to seek help. Results are not surprising, considering the
      low intensity of the campaign, especially in the media. Campaigns aimed at
      changing suicidal behaviors must be intensive.

PMID- 17219750
TI  - Gender and cultural patterns of suicidal behavior: young Hindustani immigrant
      women in the Netherlands.
AB  - Patterns of suicidal behavior vary among cultures and along gender. Young
      Hindustani immigrant women attempt suicide four times more often than young Dutch
      women. This article explores multi-disciplinary explanations for suicidal
      behavior in this group. The interconnection of Durkheimian concepts of social
      integration and regulation with ecological insights into family relations and
      psychological and psychiatric theories on individual distress are relevant. It is
      suggested that young Hindustani women who display suicidal behavior possess
      certain personality and cognitive constellations that are interlocked with
      specific parenting styles in stressful family environments. These families are
      embedded in a context of moral transformations resulting from migration to a
      Western culture and may be facing difficulties accompanying the transitional
      processes encountered in the West, particularly those regarding gender roles.
      Durkheimian fatalistic and anomic suicides elucidate this. The Hindustani women
      who appear most at risk are those facing contradictory norms and overregulation,
      which prevent them from developing autonomy.

PMID- 17219751
TI  - A review of the literature on rural suicide: risk and protective factors,
      incidence, and prevention.
AB  - BACKGROUND: Suicide is a major cause of mortality worldwide. Differences in rates
      of suicide exist between urban and rural areas; however, little rigorous research
      has examined the phenomena of rural suicide. OBJECTIVE: This review examines the
      current body of literature on rural suicide and investigates differences between
      rural and urban suicide, including socioeconomic, psychological, and cultural
      variables. Prevention and intervention strategies specific to rural communities
      are discussed. DESCRIPTION OF STUDIES: All empirical and epidemiological studies
      of rural suicide were included in the review regardless of study design or
      methodology. RESULTS: Although findings are mixed, research and epidemiological
      data indicate that suicide is a public health concern in rural areas, with
      suicide rates often greater than in urban areas. DISCUSSION: Rural locale may
      create geographic, psychological, and sociocultural barriers to treatment of
      suicide. A better understanding of the role of rurality in the development and
      maintenance of suicidal thoughts and behaviors is needed and may inform
      prevention and intervention efforts.

PMID- 17219752
TI  - Should suicide prevention programs target individuals or society as a whole?
AB  - The issue of whether it is more useful to focus on societal interventions to
      prevent suicide or individual-centered approaches is discussed. The advantages
      and drawbacks of each approach are explored.

PMID- 17219753
TI  - Statistical and regulatory issues with the application of propensity score
      analysis to nonrandomized medical device clinical studies.
AB  - Propensity score analysis is a versatile statistical method used mainly in
      observational studies for improving treatment comparison by adjusting for up to a
      relatively large number of potentially confounding covariates. Recently, there
      has been an increased interest in applying this method to nonrandomized medical
      device clinical studies. In the application of the methodology, some statistical
      and regulatory issues arise in both study design and analysis of study results,
      such as the need for pre-specifying clinically relevant covariates to be
      measured, appropriate patient populations, and the essential elements of
      statistical analysis, planning sample size in the context of propensity score
      methodology, handling missing covariates in generating propensity scores, and
      assessing the success of the propensity score method by evaluating treatment
      group overlap in terms of the distributions of propensity scores. In this paper,
      the advantages and limitations of this methodology will be revisited, and the
      above issues will be discussed and illustrated with examples from a regulatory
      perspective.

PMID- 17219754
TI  - A note on sample size calculation based on propensity analysis in nonrandomized
      trials.
AB  - In nonrandomized trials, patients are not randomly assigned to treatment groups
      with equal probability. Instead, the probability of assignment varies from
      patient to patient depending on patients baseline covariates. This often results
      in a non-comparable treatment groups due to treatment imbalance. As a result, the
      United States Food and Drug Administration (FDA) recommended that the method of
      propensity score analysis be employed to overcome this problem. In this note, a
      formula for sample size calculation is developed based on a proposed weighted
      Mantel-Haenszel test on the strata defined by the propensity score analysis. It
      was shown that the sample size formula derived by Nam (1998) based on the test
      statistic proposed by Gart (1985) is a special case of the sample size formula
      derived in this note.

PMID- 17219755
TI  - Predictive probability of success and the assessment of futility in large
      outcomes trials.
AB  - We consider a class of futility rules based on a Bayesian approach for computing
      the predictive probability of success for large clinical trials, given a certain
      amount of observed data. This paper focuses on outcomes trials in particular,
      thus we are concerned with binary response variables. The proposed method
      determines the likelihood of observing a statistically significant treatment
      effect at the end of a study, conditional on the data observed at an interim time
      point and assuming that event rates governing future observations follow beta
      distributions. In particular, the prior distributions for the event rates of
      interest are updated based on the observed data at an interim time point, such
      that means and variances are intuitive functions of the data. Computational
      aspects will be discussed for the case in which event counts are functions of
      sample size and event rates only, and for situations in which they are functions
      of sample size, event rates, and exposure duration. We will discuss appropriate
      thresholds for declaring futility based on this approach, and the potential
      impact of overdispersion, a common phenomenon particularly in global outcomes
      trials.

PMID- 17219756
TI  - The application of a Bayesian approach to the analysis of a complex,
      mechanistically based model.
AB  - The Bayesian approach has been suggested as a suitable method in the context of
      mechanistic pharmacokinetic-pharmacodynamic (PK-PD) modeling, as it allows for
      efficient use of both data and prior knowledge regarding the drug or disease
      state. However, to this day, published examples of its application to real PK-PD
      problems have been scarce. We present an example of a fully Bayesian re-analysis
      of a previously published mechanistic model describing the time course of
      circulating neutrophils in stroke patients and healthy individuals. While priors
      could be established for all population parameters in the model, not all
      variability terms were known with any degree of precision. A sensitivity analysis
      around the assigned priors used was performed by testing three different sets of
      prior values for the population variance terms for which no data were available
      in the literature: "informative", "semi-informative", and "noninformative",
      respectively. For all variability terms, inverse gamma distributions were used.
      It was possible to fit the model to the data using the "informative" priors.
      However, when the "semi-informative" and "noninformative" priors were used, it
      was impossible to accomplish convergence due to severe correlations between
      parameters. In addition, due to the complexity of the model, the process of
      defining priors and running the Markov chains was very time-consuming. We
      conclude that the present analysis represents a first example of the fully
      transparent application of Bayesian methods to a complex, mechanistic PK-PD
      problem with real data. The approach is time-consuming, but enables us to make
      use of all available information from data and scientific evidence. Thereby, it
      shows potential both for detection of data gaps and for more reliable predictions
      of various outcomes and "what if" scenarios.

PMID- 17219757
TI  - Bayesian estimation of intervention effect with pre- and post-misclassified
      binomial data.
AB  - We consider studies in which an enrolled subject tests positive on a fallible
      test. After an intervention, disease status is re-diagnosed with the same
      fallible instrument. Potential misclassification in the diagnostic test causes
      regression to the mean that biases inferences about the true intervention effect.
      The existing likelihood approach suffers in situations where either sensitivity
      or specificity is near 1. In such cases, common in many diagnostic tests,
      confidence interval coverage can often be below nominal for the likelihood
      approach. Another potential drawback of the maximum likelihood estimator (MLE)
      method is that it requires validation data to eliminate identification problems.
      We propose a Bayesian approach that offers improved performance in general, but
      substantially better performance than the MLE method in the realistic case of a
      highly accurate diagnostic test. We obtain this superior performance using no
      more information than that employed in the likelihood method. Our approach is
      also more flexible, doing without validation data if necessary, but accommodating
      multiple sources of information, if available, thereby systematically eliminating
      identification problems. We show via a simulation study that our Bayesian
      approach outperforms the MLE method, especially when the diagnostic test has high
      sensitivity, specificity, or both. We also consider a real data example for which
      the diagnostic test specificity is close to 1 (false positive probability close
      to 0).

PMID- 17219758
TI  - Use of prior information for Bayesian evaluation of bridging studies.
AB  - The ICH E5 guideline defines a bridging study as a supplementary study conducted
      in the new region to provide pharmacodynamic or clinical data on efficacy,
      safety, dosage, and dose regimen to allow extrapolation of the foreign clinical
      data to the population of the new region. Therefore, a bridging study is usually
      conducted in the new region only after the test product has been approved for
      commercial marketing in the original region based on its proven efficacy and
      safety. In this paper we address the issue of analysis of clinical data generated
      by the bridging study conducted in the new region to evaluate the similarity for
      extrapolation of the foreign clinical data to the population of the new region.
      Information on efficacy, safety, dosage, and dose regimen of the original region
      cannot be concurrently obtained from the local bridging studies but available in
      the trials conducted in the original region. Liu et al. (2002) have proposed a
      Bayesian approach to synthesize the data generated by the bridging study and
      foreign clinical data generated in the original region for assessment of
      similarity based on superior efficacy of the test product over a placebo control.
      However, the results of the bridging studies using their approach will be
      overwhelmingly dominated by the results of the original region due to an
      imbalance of sample sizes between the regions. Therefore, in this paper we
      propose a Bayesian approach with the use of a mixture prior for assessment of
      similarity between the new and original region based on the concept of positive
      treatment effect. Methods for sample size determination for the bridging study
      are also proposed. Numerical examples illustrate applications of the proposed
      procedures in different scenarios.

PMID- 17219759
TI  - Closed-form confidence intervals on measures of precision for an interlaboratory
      study.
AB  - Within the pharmaceutical industry it is common practice to transfer analytical
      methods from one laboratory to other laboratories. An experiment or
      interlaboratory study is performed to estimate the repeatability, the
      intermediate precision, and the reproducibility of the analytical method. These
      measures of precision are quantified by appropriate sums of variance components
      from an analysis of variance model describing the structure of the data. In the
      literature, several methods have been described for calculating approximate
      (closed-form) confidence intervals on sums of variance components, i.e., Welch,
      Satterthwaite, and modified large-sample (MLS). Comparisons between these methods
      have been performed for one-way and two-way classification analysis of variance
      models only. Interlaboratory studies though often need higher order
      classifications. Therefore, these methods for constructing confidence intervals
      are compared on the measures of precision from a specfic three-way classification
      analysis of variance model that is frequently used for method transfer studies.
      Using a simulation study, the coverage probability for these methods is evaluated
      in situations where variance components may be estimated negatively with the
      standard moment estimates and where either the standard moment estimates are
      adjusted to zero or remain unadjusted. The MLS method is superior to the other
      two methods in case the standard moment estimates are used. If the adjusted
      moment estimates are used, then the method of Satterthwaite performs similar to
      the MLS method for many settings of the variance components and sample sizes but
      much better for some particular settings. The method of Satterthwaite performs
      better than the method of Welch for all the selected settings of variance
      components and sample sizes, irrespective of the standard or adjusted moment
      estimates.

PMID- 17219760
TI  - Parametric two-stage sequential quality assurance test of dose content
      uniformity.
AB  - The United States Pharmacopeia (USP) content uniformity sampling acceptance plan
      consisting of a two-stage sampling plan with criteria on sample mean and number
      of out-of-range tablets is the standard for compendium. It is, however, often
      used mistakenly for lot quality assurance. In comparison to the Japan Phamacopeia
      (JP) procedure, USP procedure is less discriminative between lots with on-target
      mean and small variance and lots with off-target mean and large variance. The new
      European Pharmacopeia (EP) and USP harmonized test adopted a tolerance interval
      approach. But the "no-difference zone" criteria modification for off-target
      products make the approaches biased in favor of off-target products. We propose a
      parametric tolerance interval procedure to test a two-sided specification that is
      equivalent to the test of two one-sided hypotheses. Testing against a lower
      specification is to assure that the drug product is not under-dosed for the sake
      of efficacy. On the other hand, testing against an upper specification is to
      assure that the drug product is not over-dosed for the sake of safety. The
      operating curves of the proposed procedure are compared with those of the USP
      test to illustrate the difference in acceptance probability against the mean and
      variance of the lot.

PMID- 17219761
TI  - Missing data imputation in two phase III trials treating HIV1 infection.
AB  - In most longitudinal clinical trials, some patients drop out before the end of
      the planned follow-up, and, in order to allow an all-patient intent-to-treat
      analysis to be performed, it is common practice to use some method of imputation
      to estimate values for missing data. However, different imputation methods may
      provide different results, and it is essential to investigate the sensitivity of
      the analysis using different imputation rules. In our analysis of two trials of
      the new HIV1 fusion inhibitor enfuvirtide, we compared some standard methods of
      imputing and analyzing HIV1-RNA data with two novel alternatives, to check the
      robustness of the primary endpoint results. The standard methods were: (1) last
      observation-carried-forward, (2) baseline carried forward, and (3) multiple
      imputation. These were compared with a nearest-neighbour hot-deck method,
      specifically proposed for imputation of missing HIV1-RNA data, and with a
      heuristic approach: censored regression analysis of the last-observation-carried
      forward. To supplement this analysis of real clinical trial data, we investigated
      the performance of the same imputation methods on simulated datasets designed to
      cover a broader range of missing data patterns.

PMID- 17219762
TI  - Dose-time-response cumulative multinomial generalized linear model.
AB  - In toxicological and pharmaceutical experiments, a type of quantal bioassay
      experiment is designed in which a response, such as mortality, in a group of
      animals is recorded over time points under different dose levels in the course of
      the experiment. The application of the typical logit and probit analyses is no
      longer valid in this situation because it neglects the dependency on time and
      also the possible interaction of time and dose concentration on the response in
      the experiment. In this paper, a dose-time-response model is proposed for this
      type of experiment and a cumulative multinomial generalized linear model that
      incorporates time and the other experimental conditions as covariates is
      developed by the theory of maximum likelihood estimation. Both the point
      estimator and confidence bands for ED50(t), the concentration of a toxicant that
      will kill 50% of the animals by a specific time, t; as well as LT50(d), the time
      to 50% mortalities for a specific concentration, d, is then formulated in closed
      form from the newly proposed dose-time-response model. Finally, the newly
      proposed model is considered for a real data set to demonstrate the application.

PMID- 17219763
TI  - [Mortality study in a cohort of workers employed in a plant producing sulphuric
      acid ].
AB  - BACKGROUND: In 1992, the International Agency for Research on Cancer (IARC)
      classified sulphuric acid mists as human carcinogen, based primarily on human
      data showing increased risk for larynx cancer. Uncertainties still exist about
      other respiratory cancers. OBJECTIVES: We carried out a historical mortality
      study among workers ofa plant producing sulphuric acid in Tuscany, Italy.
      METHODS: We reconstructed a cohort of 1372 male and 37female workers with at
      least one year of employment at the plant in the period 1962-97; 46% ofthe
      workers had previously been working in pyrite mines in the area where rocks have
      a high silica content. Environmental measurements of sulphuric acid and sulphur
      dioxide from the 1970's were generally below the TLVs. Mortality was investigated
      as of August 2000; Standardized Mortality Ratios (SMR) were calculated using
      Tuscany reference rates. RESULTS: Overall mortality was below expectation (SMR
      77). In labourers, larynx cancer deaths were 4 vs 3.1 expected (SMR 130, 95% CI
      35-333), while mortality from lung cancer was below expectation (27/32.8, SMR 82,
      95% CI 54-120). An excess of myeloid leukaemia was observed mainly in workers
      without previous experience in mines (3/0.6, SMR 523, 95% CI 108-1527). Mortality
      from silicosis, but not from lung cancer, was remarkably high among workers with
      previous employment in mines. CONCLUSIONS: Among workers employed in sulphuric
      acid production, with or without previous experience in mines, we did not observe
      increased mortality from larynx or lung cancer. The increased mortality from
      myeloid leukaemia cannot be attributed to any of the exposures documented in the
      study plant and requires further investigation.

PMID- 17219764
TI  - [Noise and office work].
AB  - BACKGROUND: The problem of the assessment of noise annoyance in the workplace has
      long been a topic of discussion. Several studies led to the definition of a set
      of descriptors suitable to describe noise in the workplace and its effects in
      terms of annoyance of the subjects exposed. OBJECTIVES: The aim of the study was
      to analyse the performance of different indices in terms of correlation with
      subjective sensation, taking into account those indices which combine both the
      intensity and the spectral quality of noise. METHOD: A noise survey was carried
      out in ten ofice buildings, covering 85 rooms. Objective measurements of
      environmental noise were made together with subjective evaluations collected
      through questionnaires. Subjective ratings were then averaged and correlated with
      objective parameters. Linear regression analyses were performed in order to
      assess the reliability of objective noise indices. RESULTS: The most important
      sources of noise were face-to-face and telephone conversations. All spectra had
      excess high frequency content. Regression analysis showed that under these
      conditions most noise indics provide a reliable prediction of subjective
      annoyance. However, the best performing parameter was the A-weighted equivalent
      sound pressure level followed by the Combined Noise Index which combines noise
      intensity and its spectral quality.

PMID- 17219765
TI  - Management of impaired physicians in Europe.
AB  - INTRODUCTION: A significant percentage of physicians may be impaired at some
      point in their career by substance dependence, psychiatric and neurological
      disease. MATERIALS AND METHODS: Literature review. RESULTS: While the United
      States and a few other countries have addressed the problem since the 70's, most
      European countries still have no national or hospital policy to deal with
      impaired physicians. DISCUSSION: According to European directives on workers'
      health and safety, the occupational health physician entrusted with medical
      surveillance of hospital workers is often mandated to manage impaired
      professionals. CONCLUSIONS: Strategies for early identification, treatment and
      rehabilitation of impaired physicians are reviewed and suggestions for preventive
      action in European countries are given.

PMID- 17219766
TI  - [Cluster of malignant mesothelioma cases in a thermostat manufacturing industry].
AB  - BACKGROUND: Malignant mesothelioma is a rare disease and the identification of a
      cluster of cases suggests a possible presence of an asbestos contamination
      source. OBJECTIVES: To describe 3 cases of malignant mesothelioma (2 pleural and
      1 peritoneal) that occurred in workers employed in the same thermostat factory.
      METHODS: Since this occupational sector is not traditionally known for asbestos
      exposure the Lombardy Mesothelioma Registry proposed to Local Occupational Health
      Unit to investigate this industry. RESULTS: From the first inspection of the
      plant, an environmental asbestos contamination (ropes covering oven handle and
      gasket) was found. But the greatest source of exposure was identified in the
      melamine resin reinforced with asbestos that constituted some internal parts of
      thermostats and that were sheared and perforated by the workers. So the 3 cases
      were defined as occupational diseases and legal procedures were initiated.
      CONCLUSION: The results underline the importance of a close cooperation within
      Local Occupational Health Units and Mesothelioma Registry in the identification
      and evaluation of asbestos occupational exposure otherwise not recognized,
      determining thus the loss of precious information.

PMID- 17219767
TI  - [Usefulness of a questionnaire and RAST in screening of health care workers
      allergic to latex].
AB  - BACKGROUND: The prevalence of latex mediated IgE allergy in health care workers
      varies, according to the various studies, from 0.5% to 16. 7%. The onset of latex
      allergy involves aspects concerning the worker's health, the need for job
      transfer and possible retraining. In any case, the use of latex gloves in health
      care environments cannot be discarded, since they offer more efficacious
      protection from biological agents, compared to gloves of different materials.
      OBJECTIVES: Our objectives were to verify the prevalence of latex allergy in a
      sample of 515 health care workers and evaluate the usefulness of RAST and a
      questionnaire especially organized to identify potentially allergic subjects, at
      the same time limiting the number of false positive and false negative results.
      METHODS: 515 health care workers of the ASUR Zone7-Ancona local health unit
      accepted to answer to a questionnaire and to undergo a RAST testfor latex. Those
      with positive responses to the questionnaire or to RAST were later invited to
      undergo further allergological tests (prick and prick by prick). The
      questionnaire was revised according to the results obtained, thus increasing its
      positive predictiveness. RESULTS: Prevalence of latex allergy in our sample was
      1, 7%, positive predictiveness of RAST was rather low (31.3%), but increased
      considerably if combined with the modified questionnaire (62.5%). The Prick by
      Prick test gave more specific results than the Prick test. CONCLUSIONS: The
      proposed questionnaire can reduce the number of false positive workers needing to
      undergo further allergological tests and may be usefully applied in the screening
      of latex mediated IgE allergy in health care workers.

PMID- 17219769
TI  - Fast CYP2E1 genotyping using automated fluorescent detection.
AB  - BACKGROUND: Among polymorphic genes coding for xenobiotic-metabolizing enzymes,
      the ethanol-inducible CYP2E1 gene (1667 bp) is known to play a major role in the
      metabolism ofseveral chemicals. OBJECTIVES: In order to apply large-scale
      genotyping, we explored the use of a Single Nucleotide Primer Extension (SNuPE)
      assay coupled with automated fluorescent detection to assess the presence of low
      frequency CYP2E1*5B (c2) allele. METHODS: a classic PCR-RFLP (Polymerase Chain
      Reaction-Restriction Fragment Length Polymorphism) method specific for
      polymorphic5'-flanking region of CYP2E1 gene was tested in conjunction with a
      newly developed accelerated SNuPE assay. RESULTS: compared to the classic PCR
      RFLP method, the accelerated SNuPE assay proved to be both sensitive and specific
      for fast CYP2E1 genotyping. CONCLUSIONS: automated fluorescent methods as SNuPE
      assay are usefulfor public health perspectives, allowing rapid genotyping of
      metabolic genes in large population studies in clinical or epidemiological
      settings.

PMID- 17219768
TI  - [Occupational accidents among immigrant workers in the Fabriano areas].
AB  - BACKGROUND: The growing contribution of immigrant workers to the national economy
      particularly affects the trend of accidents at work. OBJECTIVES: The aim of this
      study was to describe the trend of work accidents in the Local Health Area No. 6 
      Fabriano (Marche Region), during the period 2000-2003; to define the frequency
      for each job sector, age, gender, type of work, severity, month, day and week and
      time of day; to calculate the incidence rate for each year taken into
      consideration. METHODS: The sources of information used were: 1) The "New
      Informative Flows" database set up by Italian National Institute of Insurance for
      Occupational Injury (INAIL), Italian Superior Institute for Work Prevention and
      Safety (ISPESL) and Regional Governments, and the "EPIWORK software", for the
      total number of occupational accidents among immigrant workers. 2) The local Jobs
      and Training Centre of Fabriano. We used three different correction indexes to
      evaluate the number of hired workers so as to estimate the rate of accident
      incidence among immigrant workers. RESULTS: The total number of occupational
      accidents reached its peak in 2001 as a result of the rise in the number of
      employed people. After this date, the trend started to reverse and in 2002 an
      increase in the number of employed people--although smaller compared to the
      previous year--was accompanied by a reduction in the overall number of accidents,
      a reduction that became even more evident in 2003. Occupational accidents among
      immigrant workers gradually rose and peaked in 2002. The sectors with high rates
      of accidents were the mechanical engineering and metallurgic sectors and the
      construction industry. Accidents occurred mainly among young people (18 to
      34years old). As for gender, there was a marked prevalence of men (83.3%) over
      women (16.7%). Most accidents had a prognosis of 8 to 30 days. The number
      ofoccupational accidents with a prognosis of 8 to 30 days fell progressively for
      workers in general but gradually rose for immigrant workers with a peak in 2001.
      The overall number of occupational accidents that caused permanent invalidity
      fell by 52.3% for the workforce in general, and by 25% among immigrant workers.
      CONCLUSIONS: This study shows that immigrant workers employed in the Fabriano
      area had a higher risk of accidents at work.

PMID- 17219770
TI  - [Noise damage, report to the judicial authority and natural history of the
      report].

PMID- 17219771
TI  - [Systematic research and etiological diagnosis of lung tumors].

PMID- 17219772
TI  - Centennial Declaration of the International Commission on Occupational Health,
      ICOH.

PMID- 17219773
TI  - The Declaration of Brescia on Prevention of the Neurotoxicity of Metals Brescia,
      Italia 17-18 June 2006.

PMID- 17219774
TI  - Lodi Declaration on Healthy Villages--Adopted by the 16th International Congress
      of Agricultural Medicine and Rural Health, Lodi, Italy, 18 - 21 June 2006.

PMID- 17219775
TI  - Dietary prevention of hormone refractory prostate cancer in Lobund-Wistar rats: a
      review of studies in a relevant animal model.
AB  - Lobund-Wistar (LW) rats, which have high testosterone levels, are predisposed to
      develop hormone-refractory prostate cancer (HRPC) spontaneously and by
      methylnitrosourea (MNU) induction, and the development of HRPC progresses through
      2 stages. This paper reviews several studies in which LW rats were placed on soy
      containing diets and were evaluated for development of either spontaneous or MNU
      induced prostate cancer. The premalignant, testosterone-dependent stage is
      inhibited by testosterone deprivation. In the absence of testosterone
      deprivation, tumorigenesis progresses spontaneously to the testosterone
      independent refractory stage. In LW rats: moderate caloric restriction prevented
      development of spontaneous prostate cancer; dietary 4-hydroxyphenylretinamide
      prevented MNU-induced prostate cancer; and dietary supplementation with soy
      protein isolate with high isoflavones prevented spontaneous and induced tumors
      and led to moderate reduction of serum testosterone. In rats 12 mo of age and
      younger, changing from the control diet to the soy+isoflavone diet significantly
      prevented progression of spontaneous tumors to the refractory stage of disease.
      Tumors that developed spontaneously and after MNU induction showed similar
      developmental stages and morphology, but MNU-induced tumors had shorter latency
      periods before development. The accumulated data indicate that soy-based diets
      are effective in the prevention of prostate cancer.

PMID- 17219776
TI  - Heritable, diet-induced hyperlipidemia in California mice (Peromyscus
      californicus) is due to increased hepatic secretion of very low density
      lipoprotein triacylglycerol.
AB  - California mice (Peromyscus californicus) develop type II diabetes mellitus when
      fed a high-fat diet. We undertook the current studies to determine whether
      hyperlipidemia precedes the development of insulin resistance and to establish
      breeding colonies of hyperlipidemic and normolipidemic mice. For 6 wk, mice (n =
      24) received a diet containing 25.8% of energy from fat. Mice representing the
      upper and lower quartiles of serum triacylglycerol (TAG) response (mean, >1000
      mg/dl versus <300 mg/dl, respectively; 6 mice per group) were designated as high
      (HR) and low (LR) responders, respectively, and were used for further study.
      After 12 wk of consuming the high-fat diet, HR mice remained hypertriglyceridemic
      and developed hyperinsulinemia (5.1 +/- 1.3 ng/ml), hypercholesterolemia (309.3
      +/- 31.0 mg/dl), and hyperglycemia (205.9 +/- 30.3 mg/dl) compared with LR mice.
      HR mice were not hyperphagic or obese. Offspring of HR x HR mice had elevated
      serum TAG concentrations (mean, 1752.2 +/- 209.7 mg/dl), hypercholesterolemia,
      hyperinsulinemia, and mild hyperglycemia by 5.5 mo of age. Mating HR male and LR
      female mice produced HR, intermediate, and LR progeny. HR mice had elevated serum
      concentrations of cholesterol, and plasma concentrations of high density
      lipoprotein cholesterol, and the very low density lipoprotein TAG compared with
      LR mice. Lipoprotein lipase and hepatic lipase activities did not differ between
      HR and LR mice. Studies of in vivo hepatic TAG production indicated that the
      hyperlipidemia of HR mice is a consequence of TAG hypersecretion.

PMID- 17219777
TI  - The circling mouse (C57BL/6J-cir) has a 40-kilobase genomic deletion that
      includes the transmembrane inner ear (tmie) gene.
AB  - The circling mouse (C57BL6-cir) shows deafness and circling behavior in
      homozygotes. The mutation is transmitted with 100% penetrance by an autosomal
      recessive gene on chromosome 9. In the present study, we characterized the
      circling mutation as a 40-kilobase deletion that includes the transmembrane inner
      ear (tmie) gene. The tmie gene was first identified because its mutation causes
      deafness and circling behavior in spinner mice. We suggest that the genomic
      deletion of circling mice is a different, but allelic, mutation to that of
      spinner mice. In addition, during general behavioral investigations for
      complementation tests of the 2 strains, we found that circling and spinner mice
      may differ in their behavioral responses to a new environment.

PMID- 17219778
TI  - Validation of high-throughput methods for measuring blood urea nitrogen and
      urinary albumin concentrations in mice.
AB  - Chronic kidney disease is a substantial medical and economic burden. Animal
      models, including mice, are a crucial component of kidney disease research;
      however, recent studies disprove the ability of autoanalyzer methods to
      accurately quantify plasma creatinine levels, an established marker of kidney
      disease, in mice. Therefore, we validated autoanalyzer methods for measuring
      blood urea nitrogen (BUN) and urinary albumin concentrations, 2 common markers of
      kidney disease, in samples from mice. We used high-performance liquid
      chromatography to validate BUN concentrations measured using an autoanalyzer, and
      we utilized mouse albumin standards to determine the accuracy of the autoanalyzer
      over a wide range of albumin concentrations. We observed a significant, linear
      correlation between BUN concentrations measured by autoanalyzer and high
      performance liquid chromatography. We also found a linear relationship between
      known and measured albumin concentrations, although the autoanalyzer method
      underestimated the known amount of albumin by 3.5- to 4-fold. We confirmed that
      plasma and urine constituents do not interfere with the autoanalyzer methods for
      measuring BUN and urinary albumin concentrations. In addition, we verified BUN
      and albuminuria as useful markers to detect kidney disease in aged mice and mice
      with 5/6-nephrectomy. We conclude that autoanalyzer methods are suitable for high
      throughput analysis of BUN and albumin concentrations in mice. The autoanalyzer
      accurately quantifies BUN concentrations in mouse plasma samples and is useful
      for measuring urinary albumin concentrations when used with mouse albumin
      standards.

PMID- 17219779
TI  - A single dose of liposome-encapsulated hydromorphone provides extended analgesia
      in a rat model of neuropathic pain.
AB  - Opioids have been shown to relieve thermal hyperalgesia associated with
      neuropathic pain. We used a novel technique to produce liposome-encapsulated
      hydromorphone (LEH), which we then tested in a chronic constriction injury (CCI)
      thermal hyperalgesia model of neuropathic pain. Rats were divided into sham
      operated and CCI groups. Treatments consisted of LEH or standard hydromorphone,
      administered at surgery or 3 d after surgery, when thermal hyperalgesia had
      developed in the CCI rats. We measured thermal withdrawal latencies on days 0, 3,
      and 5. CCI rats given liposome-encapsulated vehicle or standard hydromorphone at
      surgery developed full thermal hyperalgesia. CCI rats given LEH at surgery
      exhibited no significant change compared with baseline values in thermal
      withdrawal latency, indicating that this preparation prevented hyperalgesia after
      a single injection. CCI rats given LEH on day 3 (that is, after they had
      developed hyperalgesia) showed reversal of hyperalgesia that persisted to day 5,
      whereas CCI rats given standard hydromorphone on day 3 showed only brief
      (approximately 90 min) reversal of hyperalgesia. Preemptive injection of LEH
      prevented hyperalgesia in this model for as long as 5 d. In addition,
      hyperalgesia was alleviated for at least 2 d after injection of a single dose of
      LEH. These results suggest that liposome-encapsulation of hydromorphone offers a
      convenient and effective means to provide relief from neuropathic pain in this
      rodent model.

PMID- 17219780
TI  - Sodium ascorbate and basic fibroblast growth factor protect muscle-derived cells
      from H2O2-induced oxidative stress.
AB  - Engraftment of muscle-derived cells (MDCs) into the urethral sphincter may cure
      urinary incontinence. However, poor cell survival after injection prompted us to
      evaluate whether 24-h preincubation with sodium ascorbate (ASC) or basic
      fibroblast growth factor (bFGF) prior to cell transfer improves the survival of
      MDCs facing oxidative stress in vitro. We examined MDCs isolated from female rats
      for the presence of myogenic markers and for the ability to differentiate and
      respond to growth factors. Isolated cells were positive for desmin, M-cadherin,
      and myogenin. The fusion index exceeded 29%, and Akt kinase was phosphorylated at
      Ser473 residue upon exposure to insulin-like growth factor 1 (100 ng/ml). We then
      autologously transplanted MDCs transfected with lacZ marker gene into urethral
      wall of the rats; 2 wk later, the urethra and caudal wall of the urinary bladder
      were harvested from these animals. Serial cryosections revealed that transplanted
      cells formed multinuclear clusters at injection sites. In addition, we found that
      the viability of MDCs exposed to a cytotoxic concentration of H2O2 was higher
      after preincubation with 0.1 mM ASC (2.6-fold), 10 ng/ml bFGF (2.9-fold), or 20
      ng/ml bFGF (3.5-fold) than that after exposure to H2O2 only. We conclude that
      preincubation with ASC or bFGF increases the resistance of MDCs to oxidative
      stress in vitro. Pretreatment with either agent might be used to enhance survival
      of MDCs after transplantation.

PMID- 17219781
TI  - Oral treatment with retinoic acid decreases bone mass in rats.
AB  - 13-cis-retinoic acid (13-cis-RA, isotretinoin) is used to treat severe
      recalcitrant acne. Other retinoids have adverse effects on bone. Recent studies
      of human patients treated with 13-cis-RA have had varying results, perhaps
      because of variability among patients and the lack of control groups. The effects
      of retinoids have been studied in rodents, but little information is available
      regarding the effects of clinically relevant retinoid doses as evaluated by use
      of bone densitometric techniques. We treated rats for 15 or 20 wk with 13-cis-RA,
      all-trans-RA, or soybean oil (control) by gavage. We used dual-energy X-ray
      absorptiometry, histomorphometry, and histologic evaluation to evaluate effects
      on bone. Spontaneous long bone fractures occurred in some rats treated with 15
      mg/kg all-trans-RA daily. Bone mineral density, bone mineral content, bone
      diameter, and cortical thickness of the femur were reduced in rats treated daily
      with 10 or 15 mg/kg all-trans-RA or 30 mg/kg 13-cis-RA. The lumbar spine was not
      affected. Although the effects of 13-cis-RA were not as dramatic as those of all
      trans-RA, further study of the effects of 13-cis-RA on long bones is warranted.

PMID- 17219782
TI  - Electrocardiogram abnormalities in captive chimpanzees (Pan troglodytes).
AB  - Although cardiovascular disease is the leading cause of death in the captive
      chimpanzee population, little is known about the prevalence and etiology of heart
      disease in this species. We reviewed the physical exam records of 265 common
      chimpanzees (Pan troglodytes) for electrocardiogram abnormalities. During the 24
      mo period reviewed (August 2003 through August 2005), 34 animals were diagnosed
      with cardiac arrhythmias consisting of ventricular arrhythmias, supraventricular
      arrhythmias, conduction disturbances, mixed arrhythmias, and bradycardia. The
      incidence of cardiac arrhythmia was significantly higher in male animals,
      chimpanzees 20 to 39 y old, and those with structural heart disease. Incidence of
      cardiac arrhythmia was not significantly higher in animals with hypertension,
      hyperlipidemia, or chronic viral infections. During the retrospective period, 7
      animals with cardiac arrhythmias died or were euthanized. Mortality was
      significantly higher in animals with ventricular arrhythmias compared with those
      without ventricular arrhythmias. We conclude that in the common chimpanzee, age,
      male gender, and structural heart disease are risk factors for developing cardiac
      arrhythmias and that ventricular arrhythmias are risk factors for mortality.

PMID- 17219783
TI  - AALAS position stement on the humane care and use of laboratory animals.

PMID- 17219784
TI  - Acute mountain sickness: influence of fluid intake.
AB  - OBJECTIVE: High altitude and exposure to cold are associated with significant
      levels of dehydration because of cold-altitude urine output, high energy
      expenditures, and poor access to water. The aims of the present study were to
      measure the fluid intake and urine output among military mountaineers during
      their stay at high altitude and to study the level of fluid intake and decrease
      in urine output in relation with acute mountain sickness (AMS). METHODS: This
      study used an analytic prospective follow-up design of hydration-dehydration
      conditions of a group of mountaineers with similar characteristics (military
      group). Data collected each day included quantity and type of fluid intake, urine
      output in 24 hours, other fluid output (as diarrhea or vomiting), and symptoms or
      signs of AMS according to the Lake Louise consensus score. Values are given as
      mean +/- SE. A 1-factor analysis of variance procedure and t test were used to
      compare variables. RESULTS: The mountaineers consumed a variety of fluids,
      including water, tea, coffee, soup, Isostar, and milk. Daily fluid intake was
      2800 +/- 979 mL, with a maximum intake of 4700 mL. Daily urine output was 1557 +/
      758 mL. When we stratify our sample at the median by fluid intake, a significant
      correlation is detected with mean balance and mean urine output. Mountaineers
      developing AMS demonstrated reduced urine output (mean 1336 mL) when compared
      with those without AMS (mean 1655 mL). CONCLUSIONS: We found that fluid intake
      was associated but insignificantly correlated with incidence and degree of AMS.
      Past research suggests that vigorous hydration decreases incidence and severity
      of AMS and other altitude illnesses. Our results also imply that aggressive fluid
      intake is protective, but our limited sample size yielded insufficient power to
      demonstrate a statistically significant difference.

PMID- 17219785
TI  - Variables contributing to acute mountain sickness on the summit of Mt Whitney.
AB  - OBJECTIVE: The interaction of 15 variables representing physical characteristics,
      previous altitude exposure, and ascent data was analyzed to determine their
      contribution to acute mountain sickness (AMS). METHODS: Questionnaires were
      obtained from 359 volunteers upon reaching the summit of Mt Whitney (4419 m).
      Heart rate and arterial oxygen saturation were measured with a pulse oximeter,
      and AMS was identified by Lake Louise Self-Assessment scoring. Multiple logistic
      regression analysis was used to identify significant protective and risk factors
      for AMS. RESULTS: Thirty-three percent of the sample met the criteria for AMS.
      The odds of experiencing AMS were greater for those who reported a previous
      altitude illness (adjusted odds ratio [OR] = 2.00, P < .01) or who were taking
      analgesics during the ascent (adjusted OR = 2.09, P < .01). Odds for AMS
      decreased with increasing age (adjusted OR = 0.82, P < .0001), a greater number
      of climbs above 3000 m in the past month (adjusted OR = 0.92, P < .05), and use
      of acetazolamide during the ascent (adjusted OR = 0.33, P < .05). CONCLUSIONS:
      The significant determinants of AMS on the summit of Mt Whitney were age, a
      history of altitude illness, number of climbs above 3000 m in the past month, and
      use of acetazolamide and analgesics during ascent.

PMID- 17219786
TI  - Risk factors associated with fatal animal-vehicle collisions in the United
      States, 1995-2004.
AB  - OBJECTIVE: Animal-vehicle collisions are a significant public health concern in
      the United States. The annual economic cost currently exceeds $1 billion from
      injuries and property damage. A recent study by the Centers for Disease Control
      and Prevention evaluated nonfatal injuries from animal-vehicle collisions, but
      information on fatal animal-vehicle collisions is limited. This study evaluates
      risk factors associated with fatal animal-vehicle collisions. METHODS: This study
      evaluates characteristics of fatal animal-vehicle collisions in the United States
      from 1995-2004 by using the Fatality Accident Reporting System database of the
      National Highway Traffic Safety Administration. RESULTS: An average of 165 deaths
      occurred each year during this 10-year time period. Most deaths occurred in rural
      areas, during the fall months, on straight roads, and in clear weather, and an
      increasing trend for deaths was noted over this time period. CONCLUSION: The
      number of fatal animal-vehicle collisions is increasing. Various methods to
      reduce such collisions are described, with fencing appearing to be the most
      effective. The use of personal restraints such as seat belts in passenger
      vehicles and helmets for motorcycle and all-terrain-vehicle riders may decrease
      fatalities during a collision.

PMID- 17219787
TI  - Heart rate, mean arterial blood pressure, and pulmonary function changes
      associated with an ultraendurance triathlon.
AB  - OBJECTIVE: We studied 8 triathletes competing in the 3-day World Ultraman
      Championships (day 1: 10-km swim, 165-km bike; day 2: 261-km bike; day 3: 85-km
      run) to determine the effect of extreme physical exertion on heart rate (HR),
      mean arterial blood pressure (MAP) and pulmonary function, and their relation to
      overall athletic performance. METHODS: Baseline HR, MAP and pulmonary function
      measurements were made 2 days before the start of competition. During the
      competition, HR and MAP measurements were made less than 30 minutes before the
      start and 10 minutes after the finish each race day. Pulmonary function was
      measured within 5 minutes of the finish each race day. RESULTS: Forced vital
      capacity and forced expiratory volume in 1 second (FEV1.0) were reduced from
      baseline at the end of each race day. Peak expiratory flow (PEF) was reduced from
      baseline on days 1 and 3. Lower baseline resting HR was correlated (r = 0.77, P =
      .021) with faster total race times. The decreases in FEV1.0 and PEF over the
      whole race also correlated with performance (r = 0.77 and 0.93). Multiple
      regression analysis of baseline data indicated that HR and MAP had the strongest
      association with total race time prediction (54% and 19% of total). However, when
      declines in pulmonary function over the total race were also included, PEF was
      found to be associated with 87% of the total race time prediction. CONCLUSIONS:
      The strong association in the decline in PEF to race time, though just
      correlative, suggests a link between pulmonary function and ultratriathlon
      performance.

PMID- 17219788
TI  - Venomous adversaries: a reference to snake identification, field safety, and bite
      victim first aid for disaster-response personnel deploying into the hurricane
      prone regions of North America.
AB  - Each hurricane season, emergency-preparedness deployment teams including but not
      limited to the Office of Force Readiness and Deployment of the US Public Health
      Service, Federal Emergency Management Agency, Deployment Medical Assistance
      Teams, Veterinary Medical Assistance Teams, and the US Army and Air Force
      National Guard are at risk for deploying into hurricane-stricken areas that
      harbor indigenous hazards, including those posed by venomous snakes. North
      America is home to 2 distinct families of venomous snakes: 1) Viperidae, which
      includes the rattlesnakes, copperheads, and cottonmouths; and 2) Elapidae, in
      which the only native species are the coral snakes. Although some of these snakes
      are easily identified, some are not, and many rank among the most feared and
      misunderstood animals. This article specifically addresses all the native species
      of venomous snakes that inhabit the hurricane-prone regions of North America and
      is intended to serve as a reference to snake identification, basic field safety
      procedures, and the currently recommended first-aid measures for snakebite
      casualties.

PMID- 17219789
TI  - Caiman bite.
AB  - Caiman crocodilus, commonly called the spectacled caiman, is a very widely
      distributed resident of the western-hemisphere wetlands. Caiman bites to humans
      can cause trauma and infection. There are few reports of caiman bites; however,
      there is information about bites by other members of the same family, including
      Alligator mississippiensis. A case of acute caiman bite to the hand is described,
      including initial treatment and outcome. The bite resulted in multiple
      lacerations, interarticular fracture, and infection. One of the lacerations was
      closed, and the patient was started on moxifloxacin hydrochloride. Preventive
      care and treatment including wound care and antibiotics are discussed. The
      patient recovered with only a slight long-term functional deficit.

PMID- 17219790
TI  - Airway mucociliary function at high altitude.
AB  - Despite the presence of a number of anecdotal reports in the mountaineering
      literature, mucociliary dysfunction at high altitude has received little
      scientific attention. However, the dry, cold, thin air at high altitude has the
      potential to undermine normal mucociliary function. This seems increasingly
      likely in mountaineers who also experience dehydration, nasal obstruction, and
      extremes of aerobic respiration when climbing in such environments. These factors
      may result in a number of clinical conditions that range from sore throats and
      coughs commonly seen at altitude to rarer cases of bronchiolar collapse and lung
      atelectasis. The purpose of this review is to discuss the etiology of mucociliary
      dysfunction at altitude and outline a number of potential solutions to the
      problems this phenomenon presents.

PMID- 17219791
TI  - Human influenza A (H5N1): a brief review and recommendations for travelers.
AB  - Although avian influenza A (H5N1) is common in birds worldwide, it has only
      recently led to disease in humans. Humans who are infected with the disease
      (referred to as human influenza A [H5N1]) have a greater than 50% mortality rate.
      Currently there has not been documented sustained human-to-human transmission;
      however, should the virus mutate and make this possible, the world could
      experience an influenza pandemic. Probable risk factors for infection include
      slaughtering, defeathering, and butchering fowl; close contact with wild birds or
      caged poultry; ingestion of undercooked poultry products; direct contact with
      surfaces contaminated with poultry feces; and close contact with infected humans.
      Possible risk factors include swimming in or ingesting water contaminated with
      bird feces or dead birds and the use of unprocessed poultry feces as fertilizer.
      Clinically, early human influenza A (H5N1) resembles typical influenza illnesses,
      with fever and a preponderance of lower respiratory tract symptoms. Often,
      patients develop rapidly progressive respiratory failure and require ventilatory
      support. Treatment is primarily supportive care with the addition of antiviral
      medications. Currently, travelers to countries with both human and avian
      influenza A (H5N1) have a low risk of developing the disease. There are no
      current recommended travel restrictions. Travelers are advised to avoid contact
      with all birds, especially poultry; avoid surfaces contaminated with poultry
      feces; and avoid undercooked poultry products. The use of prophylactic antiviral
      medications is not recommended.

PMID- 17219792
TI  - Trench foot: the medical response in the first World War 1914-18.
AB  - The approaching 90-year anniversary of United States entry into the Great War is
      an apt time to examine the response to trench foot (now called nonfreezing cold
      injury [NFCI]) in this conflict. Trench foot appeared in the winter of 1914,
      characterized by pedal swelling, numbness, and pain. It was quickly recognized by
      military-medical authorities. There was little debate over whether it was
      frostbite or new condition, and it was quickly accepted as a specific disease.
      The major etiologies proposed were exposure, diet, and infection. The opinion
      emerged that it was caused by circulatory changes in the foot caused by cold,
      wet, and pressure. Predisposing factors included dietary inadequacy and fatigue.
      A number of labels were first given to the disease. However, the name "trench
      foot" was eventually officially sanctioned. Trench foot became a serious problem
      for the Allies, leading to 75 000 casualties in the British and 2000 in the
      American forces. Therapy for trench foot involved a number of conventional, tried
      and-tested, and conservative methods. Some more innovative techniques were used.
      Amputation was only used as a last resort. Prevention involved general measures
      to improve the trench environment; modification of the footwear worn by the men;
      and the provision of greases to protect them from moisture. The medical reaction
      to this condition seems to have been relatively effective. The causation was
      identified, and prophylactic measures were introduced to fit this model; these
      seem to have been successful in reducing the prevalence of the condition by 1917
      18.

PMID- 17219793
TI  - Importance of piloting a questionnaire on sexual health research.

PMID- 17219794
TI  - [Cervix uteri cancer in Poland--epidemiological opening balance and
      perspectives].
AB  - Cancer is one of the main causes of death among young and middle-aged females. In
      case of some cancer sites there is a possibility of undertaking an intervention,
      which would diminish the risk of death--to this group belongs first of all
      malignant neoplasm of cervix uteri. The date of beginning first cervix uteri
      cancer screening in Poland is approaching, therefore presenting epidemiological
      opening balance and possible scenarios of changes it worthwhile. This work uses
      data on morbidity and mortality due to malignant neoplasm of cervix uteri cancer
      in Polish population. Time trends analysis was based on so-called "breakpoint"
      (joinpoint analysis). Cervix uteri cancer mortality trend is characterized by two
      breakpoints (1971 and 1993). In the period of 1963-1970 there was an increase of
      mortality and then after the trend reversed: percentage decline was estimated at
      the level of 0.8% yearly in 1971-1992 and 2.4% yearly in 1993-2002. Hypothetical
      scenarios of changes in cervix uteri cancer mortality show, that lack of
      intervention will cause mortality among Polish females at the level recorded in
      Finland 25 years ago. Optimistic variant would allow on diminishing mortality in
      Poland down to the level observed currently in Finland, in around 30 years.
      Implementing preventive cervix uteri cancer screening is currently the most
      urgent challenge of public health. If the preventive screening program will still
      be in the phase of plans and projects, then in 30 years time Poland will be in
      the point which Finland reached in the end of 1970s, and our civilizing
      underdevelopment will reach half a century.

PMID- 17219795
TI  - [Sexual behaviour among adolescents aged 16- and 18-years in Poland in 2005].
AB  - OBJECTIVES: Presentation of: frequency of sexual debut and its age among 16- and
      18-year-olds; number of sexual partners and use contraception methods among
      sexually active adolescents. MATERIAL AND METHOD: Representative sample of
      adolescents aged 16 and 18 years in Poland, students of different type of high
      schools (N=2893; 1490 boys, 1403 girls) was used. Four questions concerning
      sexual behaviour were included in anonymous questionnaire and were derived from
      U.S. the Youth Risk Behavior Survey (YRBS). RESULTS: Among 18-year-olds 49.9% of
      boys and 47.3% of girls reported sexual debut with mean age 16.5 and 16.8 years
      respectively. 26.4% of students have had sexual intercourse at age 15 years or
      earlier. The frequency of sexual initiation increased with age, was higher among
      adolescents living in towns than in villages and was the highest among vocational
      school students. 26.3% of adolescents had three or more and 8,8% had six or more
      sexual partners. 11.1% of sexually active adolescents reported that either they
      or their partners had use any method of contraception during their last sexual
      intercourse. The most common contraception methods used was condom (it was
      reported by 82.9% of boys and 75.2% of girls). 41.1% of adolescents used
      ineffective methods: withdrawal and "natural methods". CONCLUSIONS: Approximately
      half of 18-year-olds started their sexual life. There is not gender differences
      in sexual debut frequency. The risk of unwanted pregnancy, STDs infections and
      other sexual and reproductive health problems is the highest among girls living
      in towns and students of vocational schools. The development of family planning
      and sexual and reproductive health services for young people in Poland is
      necessary.

PMID- 17219796
TI  - [Effectiveness and safety of the treatment of menopausal syndrome with Cimicifuga
      racemosa dry extract].
AB  - OBJECTIVES: Phytoestrogens could be an alternative method of the treatment of
      menopausal syndrome in women with contraindications to hormonal replacement
      therapy. DESIGN: The aim of the study was to evaluate efficacy and safety of the
      therapy with Cimicifuga racemosa dry extract. MATERIAL AND METHODS: Twenty women
      aged mean 52.4 +/- 4.9 years with climacteric syndrome were treated with
      Cimicifuga racemosa dry extract in a dose of 40 mg a day during 6 months.
      Kupperman's Index, biochemical parameters and hormonal profile were estimated
      before and after 3 and 6 months of the therapy. RESULTS: Mean values of
      Kuppermen's Index were decreased from 30.2 +/- 5.7 points before the therapy to
      8.5 +/- 6.3 points after 3 months and to 2.6 +/- 2.1 points after 6 months of the
      therapy (p < 0.05). No statistical differences in biochemical parameters'
      concentrations and hormonal profile were observed. CONCLUSIONS: Cimicifuga
      racemosa dry extract was an effective and safe therapy of climacteric women with
      contraindications to hormonal replacement therapy.

PMID- 17219797
TI  - [Inflammatory mediators and hematological parameters in cord blood in labor
      complicated by meconium-stained amniotic fluid].
AB  - OBJECTIVE: Meconium-stained amniotic fluid at term gestation is a predictor for
      adverse perinatal outcome and is associated with increased peripartum infections,
      independent of other risk factors. The aim of our study was to evaluate
      concentrations of inflammatory mediators (such as cytokine IL-6 and intracellular
      adhesion molecule ICAM-1) and values of hematological parameters of cord blood in
      presence or absence of meconium in amniotic fluid in term labor. MATERIAL AND
      METHODS: Cord blood samples were obtained from 66 term normal neonates
      immediately after birth, Soluble ICAM-1 and IL-6 concentrations were measured
      with ELISA R&D Systems kits. The umbilical blood specimen was analyzed using an
      automated hematology cell analyzer. Blood films were stained using May-Grunwald
      Giemsa method. RESULTS: There were no difference in concentrations of ICAM-1 and
      IL-6 in cord blood in groups with or without meconium-stained amniotic fluid. The
      mean count of umbilical nucleated red blood cells and white blood cells was
      significantly higher in meconium group. There was no correlation between the cord
      blood hematological values and ICAM-1 or IL-6. There was also no correlation
      between IL-6 and ICAM-I and duration of labor. The mode of delivery influenced
      cord blood IL-6 levels. CONCLUSIONS: There was no influence of meconium-stained
      amniotic fluid on cord blood IL-6 and ICAM-1 levels. Changes in hematological
      parameters in cord blood in meconium passage can suggest either fetus hypoxia or
      infection. Significant differences of concentrations of fetal IL-6 were
      associated with the mode of delivery.

PMID- 17219798
TI  - [Obstetrical results in women who underwent intrauterine invasive procedures
      during the pregnancy].
AB  - OBJECTIVE: The aim of this study was retrospective analysis of the results of
      pregnancies among women who had intrauterine invasive procedures (IIP)-
      amnioinfusion, amnioreduction, cordocentesis and shunts, based on the materials
      from Polish Mother's Memorial Hospital Research Institute in 2000-2003. MATERIAL
      AND METHODS: 320 women performed IIP: amnioinfusions due to the oligohydramnion
      (frequently connected with congenital fetal abnormalities) or premature rupture
      of membranes. Amnioreduction due to the polihydramnion (also in a twin pregnancy
      with TTTS syndrome). Implantation of shunts in fetal abnormalities-
      hydrocephalus, megabladder, CALM. Cordocentesis--diagnostic or therapeutic in a
      fetal immunisatio anty-Rh factor and fetal arrhythmias. RESULTS: The total
      percentage of pregnancy failure after IIP was 53.2%. The best results were in the
      groups with hydrocephalus and immunisatio anty Rh factor, the worst in the group
      of patients with severe oligohydramnion due to the congenital abnormalities of
      fetuses' kidney. The most frequent early complications after IIP were premature
      rupture of membranes (12.2%), fetal hypoxia (13.7%) and premature constrictions
      of uterus (8.4%). 21.3% of patients delivered in less than 5 days after IIP (
      delivery or abortion) due to the early complications or after resolving the
      obstetrical situation, e.g. the genetic reason of fetal abnormalities or lethal
      abnormalities. More complications were connected with amnioinfusion than with
      amnioreduction. Cordocentesis seemed not to be connected with more often
      appearing of fetal hypoxia. CONCLUSION: (1) IIP are connected with a big
      percentage of pregnancy failure, but it is more a result of fetal serious disease
      than a intrauterine procedure. (2) Performing an amnioinfusion or cordocentesis
      in severe oligohydramnion gives a quick diagnosis of fetal potential
      abnormalities and makes it possible to outlook the fetal prognosis. (3) Patients
      should be as early as possible qualificated to IIP to avoid complications caused
      by the primary fetal disease. (4) Patients for IIP should be carefully selected
      and prepared. They need very strict observation for a fetal well-being and
      monitoring the infective factors after the procedure.

PMID- 17219799
TI  - [The analisys of complications in forceps delivery in Institutute of Obsterics
      and Women Disease Medical University of Gdansk].
AB  - INTRODUCTION: The forceps are the oldest obstetrics instrument using to quickly
      finishing delivery in situation of imminent fetal death. Forceps delivery
      increase the risk of new-born and women complications AIM OF STUDY: The aim of
      the study was retrospective analysis of 215 forceps deliveries in Institute of
      Obstetrics and Gynecology, Medical University of Gdansk between years 1991 and
      2004. MATERIAL AND METHODS: 26653 deliveries took place in Institute of
      Obstetrics and Gynecology, Medical University of Gdansk between years 1991 and
      2004 and in 215 cases deliveries finished by forceps operations. The fetal and
      mothers complications were assessed. RESULTS: Percentage of forceps delivery was
      low 0.81%. About 30% of new-borns were born with different types of birth's
      complications. 16.7% of new-borns had extravasations of skin and 14.8% had
      subperiosteal haematoma. More than half of examined women had various injuries of
      their birth canal and the more common was unilateral rupture of cervix--18.6%.
      CONCLUSIONS: The risk of complications after forceps delivery in rather high.
      37.2% of newborn and 58,1% of women had various complications after forceps
      delivery. Our results indicate that percentage of forceps deliveries is decreased
      and in the 14 years periods was only 0.81%.

PMID- 17219800
TI  - [Frequency and layout of congenital defects in infants born from 1991 to 1995 and
      from 2000 to 2004 at the Obstetrics and Gynecology Department of Wolomin District
      Hospital].
AB  - OBJECTIVE: The aim of the study was an evaluation of the frequency and
      distribution of congenital malformations in infants born at the Obstetrics and
      Gynecology Department of Wolomin District Hospital in the years 1991-95 and 2000
      2004 and a comparison of occurrence frequency of defects' types in the analyzed
      periods. METHODS: The study comprises an evaluation of documentations of 5649
      infants born in the years 1991-1995 and 6049 infants born in the years 200-2004,
      11698 infants in total. In the study groups of infants, the frequency of
      congenital malformation occurrence was analyzed. RESULTS: The majority of
      congenital malformation diagnosis in the years 1991-1995 were CNS defects with
      21% and the second most frequent group were facial skeleton defects with 16% The
      majority of congenital malformation diagnosis in the years 2000-2004 were
      osteoarticular system defects (25%) and the second most frequent group were
      organic heart diseases with 14%. CONCLUSIONS: The frequency and distribution of
      congenital defects was comparable with data provided by other authors. The most
      frequent defects were osteoarticular system defects, congenital hart dsefects and
      CNS. An increase in number of defects of the osteoarticular system was observed.

PMID- 17219802
TI  - [Umbilical cord entanglement in monoamniotic twin preganacy--case presentation
      and literature review].
AB  - Monoamniotic twins are at most increased risk of perinatal complications with
      perinatal mortality of 28-60 % reported in literature. The most specific
      complication to monoamniotic twins is entanglement and (or) knotting of the cords
      leading to intrauterine death of both (more often) or one twin. In first
      presented case 1, 23-year-old primigravida in 33wks of twin monoamniotic
      gestation was reffered to our Institute due to intrauterine death of one co-twin
      caused by umbilical cord entanglement. In second case, 26-year-old multigravida
      in monoamniotic twin gestation was admitted to our institution. A serious
      umbilical cord entanglement was observed and a presence of true knot of umbilical
      cord was suspected. Presented cases indicate that establishing a chorionicity and
      amniocity in twin pregnancy is an essential part of ultrasound examination. The
      diagnosis of cord entanglement in monoamniotic twin pregnancy enables a
      forecasting of possible complications. According to the established diagnosis
      future protocols of perinatal management could be proposed. Due to possible
      complications counseling and management of monoamniotic twins should be performed
      in tertiary medical centers.

PMID- 17219801
TI  - [Pregnancy complicated with thrombocytopenia].
AB  - OBJECTIVE: Evaluation of the influence of the sort of thrombocytopenia and count
      of platelets on the course of pregnancy, maternal and neonatal outcomes. DESIGN:
      Retrospective analysis of 45 women, threatened of thrombocytopenia. MATERIALS AND
      METHODS: The trial population consisted of 45 women, where the following
      parameters were evaluated: age of laboring women, gestational age, the mode of
      delivery, count of platelets, bleeding complications, the need of treatment with
      steroids and platelets transfusions, as well as the birth weight of newborns, the
      Apgar score in the 1st minute, thrombocytopenia and bleeding complications in
      neonates. RESULTS: There were 27 women with gestational-induced thrombocytopenia
      and 18 women had immune thrombocytopenia. Moreover 14 had severe and 31--moderate
      thrombocytopenia. Premature labor (<37 week of pregnancy) were observed more
      often in patients with severe than in moderate thrombocytopenia (6/14-42,85% vs.
      4/31-16,13%; p < 0.05). Lower neonatal body weight (2774.28 +/- 28 vs. 3120.32 +/
      788.22; p < 0.05), Apgar score in the 1st minute (7.42 +/- 3.56 vs. 9.13 +/-
      1.56; p < 0.01), as well as neonatal complications (71.42% vs. 28.58; p < 0.01),
      were also observed more often in severe than in moderate thrombocytopenia group.
      CONCLUSIONS: The presence of antiplatelet antiobodies were associated with
      platelets count <50 x 10(3)/MICROL, the necessity of treatment with steroids and
      platelet infusions to the mother, as well as delivery of neonates with lower
      Apgar score in the 1st minute and neonatal thrombocytopenia. Severe
      thrombocytopenia was associated with the necessity of treatment with steroids and
      platelet infusions, preterm delivery, lower Apgar score in the 1st minute and
      neonatal thrombocytopenia.

PMID- 17219803
TI  - [Preconceptional and prenatal exposure to tobacco smoke and risk of childhood
      cancer].
AB  - The aim of the paper was to evaluate the association between preconceptional and
      prenatal exposure to tobacco smoke and the risk of all cancers combined and
      separately, for brain tumors, leukemias, lymphomas and other childhood cancers.
      We conducted systematic search of the literature using PUBMED, MEDLINE and EBSCO
      database to identify all publications dealing with environmental tobacco smoke
      exposure and childhood cancer.

PMID- 17219804
TI  - [Sexuality of pregnant women].
AB  - Over the time when the sexual intercourse has been considered merely one of a
      number of forms of sexual contact, views on sexuality during pregnancy have
      undergone considerable transformation. A great many of authors emphasise, that
      the pregnancy is a stimulus for partners to search for ways to maintain mutual
      emotional bond, close physical affinity and satisfy sexual needs not necessarily
      finished with an intercourse. The fact, that one of the two partners is pregnant,
      imposes some restrictions on sexual life. Not rarely, in particular in the first
      trimester of pregnancy, a female is little interested in sex. It is due to, inter
      alia, hormonal changes resulting in nausea, fatigue and increased nervosity.
      These symptoms contribute to general feebleness and reduction of the level of
      sexual needs and difficulty to become aroused and sexually ready. In spite of
      that, a lot of women have the need to keep physical and emotional contact with
      their partners. For a number of couples, pregnancy becomes a stimulus to search
      for new ways of pleasing each other in love play, that does not necessarily leads
      with an intercourse. Most studies concerning sexuality during pregnancy focus on
      observing sexual activity, physiological changes, mutual relationship of
      partners, analysis of sexual intercourses and investigation of so-called sexual
      satisfaction. Examination of sexual satisfaction ruchedes the frequency of sexual
      contacts, intercourses, foreplay, concurrence of orgasms in the two partners,
      partners' happiness, sexual satisfaction and mutual heartiness. In some
      researchers' opinion, sexual satisfaction correlates with the feeling of
      happiness resulting form being pregnant, pregnant woman's feeling still
      attractive and experience of orgasm. However, some researchers observe reduced
      sexual activity during pregnancy, except for the second trimester, when sexual
      activity is similar to the one outside pregnancy. Pregnant women prefer the
      following types of sexual activity: non-genital fondling, stimulation of the
      clitoris, vagina and breasts, oral and anal stimulation and masturbation. Females
      and their partners are underinformed on sexual life in pregnancy. The research
      indicates that 68% young mothers were not informed during pregnancy by a
      gynaecologist or midwife about sexual problems in pregnancy and, in particular,
      about possibility to derive sexual satisfaction. The research makes it evident,
      that experiencing sexual satisfaction by pregnant women improves their self
      esteem, facilitates mutual relationship between partners and tightens the marital
      bond.

PMID- 17219805
TI  - [The value of FDG PET/CT, ultrasound and CT in diagnosing recurrent ovarian
      carcinoma].
AB  - The diagnosis of recurrent ovarian cancer can be complicated and variable
      sensitivities, specificities and accuracies have been reported for integrated
      positron emission tomography and computed tomography (PET/CT). The aim of the
      study was to evaluate the sensitivity, specificity and accuracy of PET/CT,
      ultrasound and CT in the diagnosing recurrent ovarian cancer. MATERIALS AND
      METHODS: 27 women in the follow-up after cytoreductive surgery and chemotherapy
      of ovarian cancer, underwent ultrasound, CT and PET/CT to assess for possible
      recurrence. RESULTS: Recurrence of ovarian cancer was detected in 22 patients
      (laparotomy or cytology of ascites or pleural effusion). 5 disease-free patients
      were followed-up for 8-14 months. FDG-PET, ultrasound and CT had sensitivities of
      81,82%, 45,45%, 55.56%, specificities of 60%, 60%, 60% and accuracies 77,78%,
      48,15%, 52,17% respectively. CONCLUSIONS: 1. FDG PET/CT is a useful technique to
      in diagnosing recurrent ovarian cancer. 2. PET/CT depicts/detects recurrent
      ovarian cancer with higher diagnostic accuracy comparing to the standard imaging
      and provides the chance to detect disease at an earlier stage during follow-up.

PMID- 17219806
TI  - [The efficacy of transobturator tape procedure in management of stress urinary
      incontinence in women].
AB  - OBJECTIVES: The purpose of the study is to present the early outcome of stress
      urinary incontinence treatment in women using a new transobturator tape
      technique. METHODS: Between March 2004 and June 2005 67 women were operated on
      for stress urinary incontinence using the transobturator tape procedure. In 24
      patients concomitant surgery for pelvic organ prolapse was performed. The
      patients were selected to the procedure after a thorough clinical and urodynamic
      examination. During the follow-up the cure rate and postoperative complications
      were assessed after an interview and clinical examination. RESULTS: The mean
      follow-up was 13,0 months (7,2-20,7 months). In 63 out of 67 patients the stress
      urinary incontinence was completely cured. In 3 patients the procedure failed. In
      one patient with preoperative mixed urinary incontinence the bladder
      hyperreactivity did not improve. Two patients presented with early postoperative
      voiding problems demanding prolonged catheterization. CONCLUSIONS: The early
      outcome of stress urinary incontinence treatment using the transobturator tape
      procedure is very encouraging. The technique seems very effective and the
      complication risk is low. Further evaluation for long term results is of great
      interest.

PMID- 17219807
TI  - [Clinical value of the measurement of blood flow in uterine arteries and
      endometrial vessels in women with postmenopausal bleeding using "power" angio
      Doppler technique].
AB  - OBJECTIVES: The aim of the study was the measurement of blood flow in uterine
      arteries and endometrial vessels in women with postmenopausal bleeding using
      "power" angio Doppler technique MATERIALS AND METHODS: 256 patients diagnosed and
      treated because of postmenopausal bleeding participated in this study. Using
      doppler technique blood flow indices: pulsatility index (PI), resistance index
      (RI) and time average maximal velocity were measured. RESULTS: Neovascular
      arteries in endometrium were found in 87,7% patients with endometrial carcinoma,
      21,9% cases of endometrial hyperplasia and in 5,7% women with normal endometrium.
      A significantly lower PI and RI in endometrial vessels and uterine arteries were
      obtained in endometrial cancer cases than in patients with endometrial
      hyperplasia. TAMXV measured in endometrial vessels and uterine arteries was
      significantly higher in patients with endometrial cancer when compared to the
      patients with endometrial hyperplasia. CONCLUSIONS: Transvaginal ultrasonography
      with the "power" angio Doppler is a valuable diagnostic method in cases of early
      endometrial pathologies. The measurement of blood flow indices in endometrial
      vessels and uterine arteries is useful to differentiate benign and malignant
      endometrial pathologies.

PMID- 17219808
TI  - [Natural history of fetal/newborn ovarian cyst].
AB  - OBJECTIVE: Fetal and neonatal ovarian cysts are detected freguently by
      ultrasonography. Prenatal ovarian cysts have a follicular or luteal origin. Their
      natural history is a spontaneous involution. Pre- and postnatal changes in the
      sonographic aspects allow to choose the appropriate therapeutical indications:
      conservative approach, surgery, or percutaneous aspiration. MATERIALALS AND
      METHODS: In retrospective review from 1992-2004 authors present 26 patients with
      ovarian cysts. RESULTS: Fifteen patients were diagnosed by prenatal
      ultrasonography carried out between 33 and 39 weeks of gestation. Postnatally 14
      were observed only and their cysts regressed, 10 with cysts larger than 4 cm, had
      surgical exploration, 2 patients with cysts between 2 to 4 cm were candidates for
      percutaneous aspiration. CONCLUSION: 1. The conservative treatment and clinical
      observation using ultrasonography is recommended when the ovari cystic is 40 mm
      in diameter. 2. When the ovari cystic is bigger then 40 mm in diameter it is
      recommended to perform puncture and fluid aspiration from the cystis under
      ultrasonography control. 3. The surgical intervention was planned when the ovari
      cystis was heterogenous and has been growing for a few months.

PMID- 17219809
TI  - [Gastroschisis prenatally and postnatally].
AB  - OBJECTIVE: The aims of the study were: 1) evaluation of progress in surgical
      treatment of gastroschisis between 1990 and 2004 including the impact of prenatal
      diagnosis; 2) evaluation of mortality and coexisting congenital abnormalities in
      fetuses and newborns with gastroschisis. MATERIAL AND METHODS: Between 1990 and
      2004 in Polish Mother's Health Institute gastroschisis was diagnosed in 108
      cases. Basing on information from the Department of Pathology, Department of
      Pediatric Surgery and Department of Fetal Therapy, the patients were divided into
      2 groups: 1) miscarried fetuses, still born neonates and non-operated live
      newborns who died within several hours after delivery (31 cases); 2) live born
      operated on newborns (77 cases). RESULTS: Until 1999 gastroschisis was diagnosed
      prenatally only in 30% of patients, while after 1999 the defect was diagnosed in
      70% of cases. From the year 2000, due to close cooperation with obstetricians,
      newborns with gastroschisis have been operated on directly after delivery at the
      same theatre. In this period there were only 2 deaths due to prematurity (both
      twin deliveries)--5,4%. Main causes of deaths were: in group I--congenital
      defects of the cardiovascular and respiratory tracts and multiple defects; in
      group II--peritonitis, ileus due to adhesions and multiorgan failure.
      CONCLUSIONS: 1. Prenatal diagnostics and close cooperation between
      gyneacologists, obstetricians, neonatologists and pediatric surgeons
      significantly decreased mortality of newborns operated for gastroschisis in our
      Institute from 30% in 1990-1999 to 5,4 % in 2000-2004. 2. If miscarried or
      premature deliveries and deaths prior to operation are included, the mortality is
      41%. 3. Deaths in the group of non-operated patients were caused by serious
      congenital defects not connected with gastroschisis.

PMID- 17219810
TI  - [Comparison between computerized cardiotocography analysis in triplet and
      singleton pregnancies].
AB  - OBJECTIVES: Triplet pregnancies have higher perinatal morbidity and mortality
      rates than singleton pregnancies. In modern perinatology computer
      cardiotocography is one of the best methods of fetus state assessment. DESIGN:
      The research was based on computer analysis of cardiotocograph printouts.
      MATERIALS AND METHODS: The studies were made on 39 pregnant women in 27-36 week
      of gestation. The women were hospitalized in the Clinic of Perinatology I
      Department of Gynecology and Obstetrics, Medical University of Lodz and divided
      into two groups. First consisted of 30 singleton, second of 9 triplet
      pregnancies. RESULTS: Computer analysis of cardiotocograph printouts was
      performed and compared between the triplet and singleton pregnancy groups and
      presented in forms of tables. CONCLUSIONS: In the studded group of triplet
      pregnancy statistically significant higher number of high episodes,
      accelerations, fetal movements and signal loss were observed. The Apgar score and
      arterial cord pH was not different between the both groups.

PMID- 17219811
TI  - [Monitoring of labour and delivery in the presence of meconium stained amniotic
      fluid by pulse oximetry].
AB  - OBJECTIVES: Evidence of meconium-stained amniotic fluid during labor suggests
      implementation of close monitoring of fetal well-being. DESIGN: Our purpose was
      to compare fetal oxygen saturation between cases with normal and meconium stained
      amniotic fluid. MATERIALS AND METHODS: Fetal oxygen saturation was continuously
      recorded with use of Nellcor N-400 fetal pulse oximeter in 30 control cases of
      term labour of normal, and 30 cases of meconium stained amniotic fluid.
      Distribution of fetal oxygen saturation values during 5 periods of labour was
      analyzed and compared between the examined groups, and presented in forms of
      Tables, together with neonatal umbilical artery pH values, Apgar score, birth
      weight and percentage of caesarian sections performed. RESULTS: No significant
      differences in fetal oxygen saturation, neonatal umbilical artery pH, birth
      weight and caesarian sections rate were observed between analyzed groups.
      Newborns 1-th minute Apgar score (mean value) and base excess was lower in
      meconium group compared to control group. CONCLUSIONS: Our data demonstrate, that
      fetal oxygen saturation trends to decrease during labour in fetuses in both
      groups.

PMID- 17219812
TI  - [Ectopic pregnancy--still a live clinical issue --a case report].
AB  - We report a case of a 23-year old patient with extrauterine (tubal) pregnancy at
      14 weeks gestational age. The patient was admitted to the Clinic with growing
      abdominal pain lasting few hours, with worsening general condition with no
      previous symptoms. In ultrasound examination a normal size uterus was described.
      On the right and behind the uterus the structures of an alive fetus, 13 weeks
      gestational age according to biometry (BPD, FL) and a large amount of blood clots
      were seen. Laparotomy was performed and 1500 ml of blood with clots were
      evacuated from the peritoneal cavity. The right fallopian tube, bulged in isthmal
      region (close to its intramural part) was ruptured about 2 cm from the uterine
      corn. The 10 cm long fetus and afterbirth were born into the peritoneal cavity.
      Right salpingectomy was performed with no complications in the postoperative
      period.

PMID- 17219813
TI  - [Acute, hemorrhagic, overgrowing vaginal inflammation caused by Streptococcus
      agalacitae--case study].
AB  - The aim of this study was to discuss a case of an acute, hemorrhagic, overgrowing
      vaginal inflammation caused by Streptococcus agalacitae. Intravaginal globules
      based on methylcellulose and gelatin, containing a lactic acid and chitosan
      complex in mole relation 1:1 to 4:1 and, in succesion, an addition of
      hydrophilisating substances like: PEG-200, propylene-1,2 glycol or glycerol, were
      applied in the treatment process. The technology was invented in Fac. of
      pharmacy. Dep. of Pharmaceutical Technology, Wroclaw Medical Univ, Poland (recipe
      patent-protected).

PMID- 17219814
TI  - [Superfecundation in etiology of twin pregnancy].
AB  - Superfecundation is the fertilisation of two or more ova from the same cycle by
      sperm from separate acts of sexual intercourse. The term is also sometimes used
      to refer to the instances of two different males fathering fraternal twins,
      though this is more accurately known as heteropaternal superfecundation. This
      therefore leads to the possibility of twins also being half-siblings. This way of
      formation of multiply pregnancy aroused and it arouses still among doctors on
      whole world. This problem aroused large interest also among Polish doctors. For
      example, we found mention of superfecundation in first Polish medical journal, in
      Primitiae physico-medicae..., given in Leszno in years 1750-1753. Authors
      introduced relate opinion of superfecundation in aetiology of multiple
      pregnancies in historical aspect, as early as from Old Testament to present times
      as well as current state of medical knowledge of such a situation.

PMID- 17219815
TI  - [Viral hepatitis during pregnancy].
AB  - Viral hepatitis is one of the most common liver diseases appearing during
      pregnancy. Prevention against hepatotropic viruses is restricted due to lack of
      vaccines being effective in induction of efficient immunization in the majority
      of these microorganisms. In general, there is no possibility of active
      immunization against hepatotropic viruses except type A and B viral hepatitis. An
      issue of viral hepatitis in pregnancy as an aspect of potential risk factor
      connected with infection of pregnant women and a fetus has been described in this
      paper. Furthermore, the most important topics in the field of the epidemiology,
      prophylaxis and possible treatment options of viral hepatitis A, B, C, D, E and G
      have been discussed. The newest reports of pregnant women lamivudine therapy as a
      preventive treatment against vertical transmission during delivery have been
      reviewed. Rarly diagnosed viral hepatitis caused by herpes simplex virus,
      cytomegalovirus, Epstein-Barr virus and adenoviruses have been characterized as
      well.

PMID- 17219816
TI  - [Headaches in women].
AB  - Headaches are the most frequent condition in humans. Some of the primary
      headaches e.g. migraine, tension type headache and chronic paroxysmal hemicrania
      are more prevalent in women than in men. Pregnancy, lactation, breast feeding,
      withdrawal, intensify some of the primary headaches. These periods supply to some
      diseases such as eclampsia or cerebral venous thrombosis, in which headache is
      one of the main symptoms. Differential diagnosis of those headaches are very
      important, because the pharmaceutical treatment is restricted. Menstruation and
      menopause periods also cause headaches.

PMID- 17219817
TI  - Prognostic indicators.

PMID- 17219818
TI  - Progesterone and estrogen receptors: opposing prognostic indicators in
      meningiomas.
AB  - OBJECT: The preponderance of progesterone receptors (PRs) and the scarcity of
      estrogen receptors (ERs) in meningiomas are well known. The expression of PRs may
      relate to tumor grade and recurrence. Cytogenetic abnormalities are associated
      with aggressive behavior, recurrence, and progression. In this study, the authors
      focus on the prognostic implications of hormone receptors in meningiomas to help
      determine the clinical and biological aggressiveness of tumors and their
      correlations with cytogenetic abnormalities. METHODS: Two hundred thirty-nine
      patients with meningiomas were separated into three groups. Group 1 (PR-positive
      group) comprised patients whose meningiomas displayed expression of PRs alone.
      Group 2 (receptor-negative group) included patients whose lesions did not have
      receptors for either progesterone or estrogen. Group 3 (ER-positive group)
      included patients whose tumors displayed expression of ERs. Clinical and
      histological findings, proliferative indices, tumor recurrence, and cytogenetic
      findings were analyzed by performing the Fisher exact test. Compared with the
      receptor-negative (Group 2) and ER-positive (Group 3) groups, the PR-positive
      group (Group 1) had a statistically significant lower proliferative index and a
      smaller number of patients in whom there were aggressive histopathological
      findings or changes in karyotype. In Groups 1, 2, and 3, the percentages of cases
      with aggressive histopathological findings were 10, 31, and 33%, respectively;
      the percentages of cases with chromosomal abnormalities were 50, 84, and 86%,
      respectively; and the percentages of cases in which there initially was no
      residual tumor but recurrence was documented were 5, 30, and 27%, respectively. A
      statistically significant increase in the involvement of chromosomes 14 and 22
      was identified in receptor-negative and ER-positive de novo meningiomas, when
      compared with the PR-positive group. Abnormalities on chromosome 19 were
      statistically significantly higher in receptor-negative meningiomas than in PR
      positive tumors. CONCLUSIONS: The expression of the PR alone in meningiomas
      signals a favorable clinical and biological outcome. A lack of receptors or the
      presence of ERs in meningiomas correlates with an accumulation of qualitative and
      quantitative karyotype abnormalities, a higher proportional involvement of
      chromosomes 14 and 22 in de novo tumors, and an increasing potential for
      aggressive clinical behavior, progression, and recurrence of these lesions. Sex
      hormone receptor status should routinely be studied for its prognostic value,
      especially in female patients, and should be taken into account in tumor grading.
      The initial receptor status of a tumor may change in progression or recurrence of
      tumor.

PMID- 17219819
TI  - Neurostimulation for chronic noncancer pain.

PMID- 17219820
TI  - Neurostimulation for chronic noncancer pain: an evaluation of the clinical
      evidence and recommendations for future trial designs.
AB  - OBJECT: Neurostimulation to treat chronic pain includes approved and
      investigational therapies directed at the spinal cord, thalamus, periaqueductal
      or periventricular gray matter, motor cortex, and peripheral nerves. Persistent
      pain after surgery and work-related or neural injuries are common indications for
      such treatments. In light of the risks, efforts, costs, and expectations
      associated with neurostimulation therapies, a careful reexamination of the
      methods used to gather evidence for this treatment's long-term efficacy is in
      order. METHODS: The authors combed English-language publications to determine the
      nature of the evidence supporting the efficacy of neurostimulation therapies for
      chronic noncancer pain. To formulate recommendations for the design of future
      studies, the results of their analysis were compared with established guidelines
      for the evaluation of medical evidence. Evidence supporting the efficacy of
      neurostimulation has been collected predominantly from retrospective series or
      from prospective studies whose design or methods of analysis make them subject to
      limited interpretation. To date, there has been no successful clinical study
      focused on establishing the efficacy of neurostimulation for pain and
      incorporating sufficient numbers of participants, matched control groups, sham
      stimulation, randomization, prospectively defined end points, and methods for
      controlling experimental bias. Currently available data provide little support
      for the common practices of psychological or pharmacological screening or trial
      stimulation to predict and/or improve long-term results. CONCLUSIONS: These
      findings do not diminish the value of previous investigations or positive patient
      experiences and do not mean that the treatments are ineffective; rather, they
      reveal that new data are required to answer the questions raised in and by
      previous study data. Future analyses of emerging neurostimulation modalities for
      pain should, whenever feasible, require unambiguous diagnoses as an entry
      criterion and should involve the use of randomization, parallel control groups
      that receive sham stimulation, and blinding of patients, investigators, and
      device programmers. Given the chronicity of patient symptoms and stimulation
      therapies, efficacy should be studied for 1 year or longer after device
      implantation. Meticulous study methods are especially important to evaluate new
      therapies like motor cortex and occipital nerve stimulation.

PMID- 17219821
TI  - Early experience with Matrix detachable coils.

PMID- 17219822
TI  - Initial clinical experience with matrix detachable coils for the treatment of
      intracranial aneurysms.
AB  - OBJECT: The Matrix detachable coil is a new bioactive, bioabsorbable coil used in
      the endovascular embolization of intracranial aneurysms. It has a platinum core
      covered with a bioactive, bioabsorbable polymer (polyglycolic acid/lactide). The
      authors report on their initial midterm clinical experience with the first
      generation Matrix detachable coil. METHODS: One hundred twelve patients harboring
      118 aneurysms were treated using Matrix coils. Forty-nine aneurysms (41.5%) were
      associated with acute subarachnoid hemorrhage (SAH). Twenty-four lesions (49%)
      were harbored by patients with Hunt and Hess Grade I, 11 (23.4%) by patients with
      Grade II, eight (16.3%) by those with Grade III, and six (12.2%) by those with
      Grade IV. Four aneurysms (3.4%) were harbored by patients who had presented with
      nonacute SAH. Sixty-five aneurysms (55%) were unruptured. Fifty-seven lesions
      (48.3%) were small with a small neck, 29 (24.6%) were small with a wide neck, 30
      (25.4%) were large, and two (1.7%) were giant. All patients were followed up to
      obtain angiography and clinical outcome data. Technical complications occurred in
      six patients: two thromboembolic complications and four aneurysm perforations. Of
      these six patients, the status of two deteriorated because of aneurysm
      perforation and another two because of thrombus formation (morbidity 3.6%). There
      were five deaths--one due to rerupture after embolization. Angiography follow-up
      studies of 87 aneurysms were obtained. Seventy aneurysms demonstrated progressive
      occlusion or a stable neck (80.5%), and 17 had some degree of recanalization
      (19.5%). The aneurysms originally diagnosed as a neck remnant showed a 15% rate
      of recanalization. CONCLUSIONS: Matrix coils can be delivered into aneurysms with
      technical complications similar to those encountered using GDCs. Midterm
      anatomical outcomes to date have shown moderate improvement in the recanalization
      rate when compared with those realized using the GDC system. Because of the
      increased friction associated with the first-generation Matrix coil, the packing
      density in most aneurysms was less than that achieved with GDCs. Prolonged
      angiography follow-up evaluations are needed to document long-term efficacy.

PMID- 17219823
TI  - Vascular complications of vestibular schwannoma surgery: a comparison of the
      suboccipital retrosigmoid and translabyrinthine approaches.
AB  - OBJECT: Vascular complications of the surgery for vestibular schwannomas (VSs)
      can have devastating consequences; however, there is scant literature on the
      systematic analysis of the different types of complications. In this context, the
      authors of this study analyzed these complications, with particular interest in
      the role of surgical approach in their occurrence. METHODS: The charts of 391
      patients who had undergone 413 procedures for VS during a 24-year period were
      reviewed retrospectively. A suboccipital retrosigmoid (RS) approach was used in
      338 procedures, and the translabyrinthine (TL) route in 75. Postoperative
      hemorrhage or infarction was identified and stratified according to the
      complication type and surgical approach. Postoperative vascular complications
      were encountered in 11 procedures (2.7%), and their incidence was the same for
      both the RS and TL approaches. Of these complications, eight were hemorrhagic
      (two cerebellopontine angle, one intracerebellar, and five epidural hematomas)
      and three were ischemic in nature. Five patients (45.4%) had a complete recovery,
      and four patients (36.4%) a partial recovery; two patients (18.2%) died. The
      overall procedure-related mortality rate was 0.5% (two of 413 procedures): 0.3%
      (one of 338 procedures) for the RS approach and 1.3% (one of 75 procedures) for
      the TL approach (p > 0.05). CONCLUSIONS: In this study, the overall incidences of
      vascular complications in VS surgery were similar for the RS and TL approaches.
      Regardless of the preferred surgical route, this group of complications carries a
      significant risk of morbidity and therefore warrants special consideration in the
      management of VSs.

PMID- 17219824
TI  - Surgery for large vestibular schwannomas: how patients and surgeons perceive
      quality of life.
AB  - OBJECT: The aim of this study was to assess the consequences of total removal of
      a large vestibular schwannoma on the patient's symptoms and quality of life
      (QOL). METHODS: A questionnaire regarding preoperative and postoperative symptoms
      with measures of both daily and global QOL and a modified 36-Item Short Form
      Health Survey (SF-36) QOL instrument were sent to 103 patients who had undergone
      surgery via a retrosigmoid approach for total removal of a Grade III or IV
      vestibular schwannoma. In addition, 48 patients underwent follow-up clinical
      examinations to assess their conditions. Seventy-two of the 103 patients
      completed and returned the questionnaire. Forty-six (64%) of the schwannomas were
      Grade IV and 26 (36%) were Grade III. The patients' pre- and postoperative
      symptoms were similar to those reported in other studies. The patients'
      perceptions of facial movement were likely to be worse than the clinicians'
      estimation based on the House-Brackmann classification. All scores in the QOL
      categories were significantly reduced when compared with normative data. Patients
      with large vestibular schwannomas had lower scores in all SF-36 categories except
      pain compared with data from other studies. Psychological problems were the
      preponderant symptoms, and their presence was the most powerful predictive
      variable for global and daily QOL. CONCLUSIONS: Surgery for a large vestibular
      schwannoma has a significant impact on the patient's QOL. To improve QOL
      postoperatively, the patient should be prepared and well informed of the
      consequences of such a surgery on QOL. Clinicians must be aware that early
      involvement of a clinical psychologist may be very helpful.

PMID- 17219826
TI  - Effects of balloon angioplasty on perfusion- and diffusion-weighted magnetic
      resonance imaging results and outcome in patients with cerebral vasospasm.
AB  - OBJECT: The aim of this study was to analyze the effects and outcome of
      transluminal balloon angioplasty (TBA) on brain tissue perfusion by using
      combined perfusion- and diffusion-weighted (PW/DW) magnetic resonance (MR)
      imaging in patients with cerebral vasospasm after subarachnoid hemorrhage.
      METHODS: Ten consecutive patients with cerebral vasospasm treated using TBA were
      included in this prospective study. Hemodynamically relevant vasospasm was
      diagnosed using a standardized PW/DW MR imaging protocol. Digital subtraction
      angiography was used to confirm vasospasm, and TBA was performed to dilate
      vasospastic arteries. The PW/DW imaging protocol was repeated after TBA. The
      evaluation of the passage of contrast medium after standardized application using
      the bolus tracking method allowed for the calculation of the time to peak (TTP)
      before and after TBA. Tissue at risk was defined based on perfusion delays in
      individual vessel territories compared with those in reference territories. In
      cases with proximal focal vasospasm, TBA could dilate spastic arteries. Follow-up
      PW/DW MR imaging showed the disappearance of, or a decrease in, the mismatch. A
      TBA-induced reduction in the perfusion delay of 6.2 +/- 1 seconds (mean +/-
      standard error of the mean) to 1.5 +/- 0.45 seconds resulted in the complete
      prevention of infarction; a reduction in the delay of 6.2 +/- 2.7 to 4.1 +/- 1.9
      seconds resulted in the preservation of those brain tissue parts having only
      small infarcts in the vessel territories. Without TBA, however, the perfusion
      delay remained or even increased (11.1 +/- 3.7 seconds), and the complete
      infarction of a territory occurred. CONCLUSIONS: Angioplasty of vasospastic
      arteries leads to hemodynamic effects that can be quantified using PW/DW MR
      imaging. In cases of a severe PW/DW imaging mismatch successful TBA improved
      tissue perfusion and prevented cerebral infarction. The clinical significance of
      PW/DW MR imaging and the concept of tissue at risk is shown by cerebral
      infarction in vessels not accessible by TBA.

PMID- 17219825
TI  - Gamma knife surgery for metastatic brainstem tumors.
AB  - OBJECT: The authors review imaging and clinical outcomes in patients with
      metastatic brainstem tumors treated using Gamma Knife surgery (GKS). METHODS:
      Between March 1989 and March 2005, 53 patients (24 men and 29 women) with
      metastatic brainstem lesions underwent GKS. The metastatic deposits were located
      in the midbrain in eight patients, the pons in 42, and the medulla oblongata in
      three. Lung cancer was the most common primary malignancy, followed by breast
      cancer, melanoma, and renal cell carcinoma. The mean volume of the metastatic
      deposits at the time of treatment was 2.8 cm3 (range 0.05-21 cm3). The
      prescription doses varied from 9 to 25 Gy (mean 17.6 Gy). Imaging follow-up
      studies were not completed in 16 patients, because of the short-term survival in
      11 and patient refusal in five. Of the remaining 37 patients, who underwent an
      imaging follow-up evaluation at a mean of 9.8 months (range 1-25 months), the
      tumors disappeared in seven, shrank in 22, remained unchanged in three, and grew
      in five. All but one of 18 patients with asymptomatic brainstem deposits remained
      free of symptoms. In 35 patients with symptomatic brainstem deposits,
      neurological symptoms improved in 21, remained stable in 11, and worsened in
      three. At the time of this study, 10 patients were alive, and their survival
      ranged from 3 to 52 months after treatment. Thirty-four patients died of
      extracranial disease, three of the progressing metastatic brainstem lesion, and
      six of additional progressing intracranial deposits in other parts of the brain.
      The overall median survival period was 11 months after GKS. In terms of survival,
      the absence of active extracranial disease was the only favorable prognostic
      factor. Neither previous whole-brain radiation therapy nor a single brainstem
      metastasis was statistically related to the duration of survival. CONCLUSIONS:
      Compared with allowing a metastatic brainstem lesion to take its natural course,
      GKS prolongs survival. The risks associated with such treatment are low. The
      severity of systemic diseases largely determines the prognosis of metastases to
      the brainstem.

PMID- 17219827
TI  - Magnetic resonance angiography and clinical evaluation of third nerve palsies and
      posterior communicating artery aneurysms.
AB  - OBJECT: The authors conducted a study to determine the utility of the clinical
      profile and magnetic resonance (MR) angiography in evaluating patients with
      isolated third cranial nerve palsies or posterior communicating artery (PCoA)
      aneurysms. METHODS: Three-dimensional time-of-flight MR angiography was performed
      in a consecutive series of patients with isolated acute third cranial nerve palsy
      not due to a ruptured aneurysm and in patients with unruptured PCoA aneurysms. A
      neuroradiologist, masked to the identities of the patients, interpreted
      reformatted maximum intensity projection (MIP) and source images of the PCoAs and
      aneurysms. The investigators assessed clinical features of oculomotor nerve
      dysfunction and focal head pain. Cases involving cranial third nerve palsy
      without aneurysms were classified as Group 1 (no case entailed catheter-based
      angiography), and cases involving PCoA aneurysms seen on MR angiography (42 cases
      confirmed by catheter-based angiography) were classified as Group 2. The mean age
      of the 73 patients in Group 1 was 60.1 years and that of the 45 patients in Group
      2 was 59.1 years (p = 0.37). The pattern and severity of oculomotor (p = 0.61)
      and lid (p = 0.83) dysfunction and pain frequency (p = 0.2) were similar for the
      73 patients with vasculopathy in Group 1 and the 15 symptomatic patients in Group
      2. Abnormal pupils were observed in 38% of the patients in Group 1 and 80% of
      those in Group 2 (p = 0.016). In cases of complete external third nerve palsy,
      nine of 22 in Group 1 and none of four in Group 2 had normal pupil function. For
      all patients, source imaging showed 206 PCoAs (85%) and MIP imaging demonstrated
      120 PCoAs (49%). Of 48 aneurysms (three bilateral), MIP imaging showed 44 (92%)
      and source imaging showed 47 (98%). Only a 2-mm aneurysm seen on catheter-based
      angiography was missed by MR angiography. Symptomatic aneurysms were equal or
      greater than 4 mm in size. CONCLUSIONS: Only the presence of complete external
      third nerve palsy and normal pupil function allowed ischemia to be clinically
      distinguished from a PCoA aneurysm in a patient with isolated third nerve palsy
      and no subarachnoid hemorrhage. When source image MR angiography demonstrates
      normal findings, catheter-based angiography need not be performed in these
      patients, even if pupil function is abnormal.

PMID- 17219828
TI  - Primary stent therapy for symptomatic intracranial atherosclerotic stenosis: 1
      year follow-up angiographic and midterm clinical outcomes.
AB  - OBJECT: The aim of this study was to report 1-year angiographic follow-up results
      and midterm clinical outcomes in patients with symptomatic intracranial
      atherosclerotic lesions treated with stent placement. METHODS: Ten patients with
      ischemic symptoms referable to stenotic intracranial atherosclerotic arteries,
      with greater than 60% stenosis, underwent elective surgery in which a primary
      stent was placed. All patients underwent pretreatment (> or =1 week) combination
      oral antiplatelet (clopidogrel and aspirin) therapy and long-term (6-month)
      combination oral antiplatelet (clopidogrel and aspirin) therapy after stents were
      placed. The procedure involved selecting stents of the same size as the diameter
      of the target vessel and slowly inflating the balloon to its nominal pressure.
      One-year angiography and midterm clinical follow-up data were obtained. The
      stents were successfully placed in all patients without any perioperative
      complication. The mean preoperative stenosis rate of 81% decreased to 4% after
      the stent was placed. Nine patients who underwent follow-up angiography (one
      patient refused) at a mean of 12.3 months (range 10-19 months) had no changes in
      luminal diameter compared with the immediate postoperative luminal diameter.
      Luminal narrowing increased, from 15 to 38%, in one case in which there was
      comparatively greater residual stenosis (15%). No patient suffered new ischemic
      symptoms during a mean clinical follow-up period of 21 months (range 12-36
      months). CONCLUSIONS: Elective stent surgery can provide good angiographic and
      clinical midterm outcomes in patients with symptomatic intracranial
      atherosclerotic stenosis, and the procedure is associated with a high degree of
      technical success. Reassessment of these promising results is needed in a larger
      population and in a randomized prospective comparison study.

PMID- 17219829
TI  - Surgical shunt infection: significant reduction when using intraventricular and
      systemic antibiotic agents.
AB  - OBJECT: Infection represents the most common serious complication of shunt
      surgery, and typically its incidence ranges between 5 and 15%, despite the use of
      systemic antibiotic agents. Because systemic antibiotic medications generally
      penetrate the cerebrospinal fluid (CSF) poorly, the authors investigated, in a
      controlled study, whether the addition of intraventricular antibiotic treatment
      decreases the incidence of perioperative infection in adult patients. METHODS:
      Data pertaining to all CSF shunt procedures conducted at the authors' institution
      during an 11-year period were reviewed. Perioperative infection was defined as
      culture-positive CSF and the clinical presence of infection-related symptoms
      occurring within 90 days of surgery. All patients underwent intraoperative
      systemic antistaphylococcal antibiotic therapy. Before May 16, 1999, the senior
      author (R.H.S.) also administered 4 mg of gentamicin intraventricularly at
      surgery (Group I); thereafter, 10 mg of vancomycin was additionally administered
      (Group II). Other neurosurgeons at this institution did not use intraventricular
      antibiotic therapy, and their patients served as additional controls in identical
      time periods (Groups III and IV). A total of 802 shunt procedures were performed
      in 534 patients. Control infection rates were 5.4% (eight of 147) in Group I;
      6.2% (nine of 145) in Group III; and 6.7% (18 of 267) in Group IV. With the
      combination of systemic antibiotic and intraventricular gentamicin and vancomycin
      (Group II), the infection rate fell significantly to 0.4% (one of 243). No
      complications were noted in association with intraventricular antibiotic
      administration. CONCLUSIONS: The combination of intraventricular gentamicin and
      vancomycin with systemic antibiotic therapy significantly decreased the incidence
      of perioperative shunt infection. It is presumed that intraventricular antibiotic
      therapy extends prophylactic antibiotic coverage into the CSF and prevents
      bacterial seeding.

PMID- 17219830
TI  - Long-term natural history of hemangioblastomas in patients with von Hippel-Lindau
      disease: implications for treatment.
AB  - OBJECT: In the course of their lives most patients with von Hippel-Lindau (VHL)
      disease require treatment for several symptom-producing hemangioblastomas of the
      cerebellum, brainstem, or spinal cord. However, many tumors never produce
      symptoms and do not require treatment. Detection at an early stage of lesions
      that will later produce symptoms and ultimately require treatment would allow for
      earlier excision of hemangioblastomas of the spinal cord, brainstem, or
      cerebellum, and may identify cerebellar hemangioblastomas that can be treated
      with radiosurgery at a stage before treatment is contraindicated because of tumor
      size or the presence of an associated cyst. METHODS: To identify features
      predictive of symptom development that might allow for earlier treatment of
      smaller, presymptomatic hemangioblastomas in patients with VHL disease, the
      authors reviewed and analyzed the serial clinical and imaging findings in all
      patients with VHL disease who were followed up at the National Institutes of
      Health for more than 10 years. Features predictive of symptom formation were
      determined by recursive partition and regression analyses. Nineteen patients (10
      men and nine women; mean age 32.6 +/- 11.6 years) harboring a total of 143
      hemangioblastomas were identified (mean follow-up duration 12.4 +/- 1.4 years).
      Hemangioblastomas were located in the cerebellum (68 hemangioblastomas, 48% of
      patients), brainstem (17 hemangioblastomas, 12% of patients), and spinal cord (58
      hemangioblastomas, 40% of patients). Despite measurable growth in almost all
      hemangioblastomas (138 lesions, 97% of patients), only 58 (41% of patients)
      became symptomatic. Hemangioblastomas grew in a stuttering pattern. (mean growth
      period 13 +/- 15 months, mean quiescent period 25 +/- 19 months). Twenty-six
      (45%) of the hemangioblastomas that eventually produced symptoms were not among
      the tumors that were apparent on the initial MR imaging study. Depending on
      location, the hemangioblastoma size and/or tumor and cyst growth rates predicted
      symptom development and the need for treatment (p < 0.05). Cerebellar
      hemangioblastomas growing faster than 112 mm3/ month or larger than 69 mm3 with
      associated tumor and cyst growth rates greater than 14 mm3/month became
      symptomatic (100% sensitivity, 72% specificity). Brainstem hemangioblastomas
      larger than 245 mm3 with growth rates greater than 0.1 mm3/month became
      symptomatic (75% sensitivity, 89% specificity). Spinal hemangioblastomas larger
      than 22 mm3 became symptomatic (79% sensitivity, 94% specificity). CONCLUSIONS:
      Because hemangioblastomas exhibit a stuttering growth pattern, frequently remain
      asymptomatic, and do not require treatment for long intervals, unqualified
      radiographic progression is not an indication for treatment. Basing the decision
      to intervene in individual tumors solely on radiographic progression would have
      resulted in approximately four additional procedures per patient during the 10
      year study period. Threshold values are presented for tumor size and/or tumor and
      cyst growth rates that can be used to predict symptom formation and future need
      for treatment.

PMID- 17219831
TI  - Metastases to hemangioblastomas in von Hippel-Lindau disease.
AB  - OBJECT: Patients with hereditary cancer syndromes may be at increased risk for
      the development of tumor-to-tumor metastases. To gain insight into the biological
      nature of these lesions in the central nervous system (CNS), to determine their
      prevalence in a familial neoplasia syndrome, and to better define their
      management, the authors retrospectively examined a series of cases in which
      metastatic lesions developed within hemangioblastomas in patients with von Hippel
      Lindau (VHL) disease. METHODS: The study included all cases of VHL disease in
      which patients underwent resection of a CNS hemangioblastoma that contained a
      metastasis or were found at autopsy to have a metastasis to a hemangioblastoma
      between January 2002 and December 2005 at the National Institute of Neurological
      Disorders and Stroke (NINDS). Clinical, histopathological, imaging, and surgical
      and/or autopsy findings were analyzed. Metastasis to a CNS hemangioblastoma was
      found in six resected tumors (8% of all hemangioblastomas resected from patients
      with VHL disease at the NINDS during the study period) from six patients (five
      women, one man; mean age at surgery 42.5 years). The primary site of metastatic
      disease was the kidney in five patients (renal cell carcinoma) and the pancreas
      in one (a pancreatic neuroendocrine tumor). Only one patient had systemic
      metastases at the time of resection of the hemangioblastoma containing the
      metastasis. Neurologically, all patients had remained at baseline or were
      improved at last clinical follow-up examination (mean follow-up duration 16.5
      months, range 3-40 months). In all cases, postoperative imaging revealed that the
      hemangioblastoma resection was complete, and there was no evidence of recurrence
      in any of the patients at the last follow up. Two patients (including one who was
      also in the surgical group) were found at autopsy to have CNS metastases
      exclusively to spinal hemangioblastomas. CONCLUSIONS: Hemangioblastomas are an
      early and preferred site for metastasis in VHL disease. Emerging
      histopathological techniques may lead to recognition of an increasing number of
      cases of tumor-to-hemangioblastoma metastasis. Management of cases involving
      tumor-to-hemangioblastoma metastases in VHL disease should be based on the
      histological characteristics of the primary tumor, extent of the primary disease,
      and completeness of the resection.

PMID- 17219832
TI  - Tako-tsubo cardiomyopathy in aneurysmal subarachnoid hemorrhage: an
      underappreciated ventricular dysfunction.
AB  - OBJECT: Neurogenic stunned myocardium in aneurysmal subarachnoid hemorrhage (SAH)
      is associated with a wide spectrum of reversible left ventricular wall motion
      abnormalities and includes a subset of patients with a pattern of apical akinesia
      and concomitant sparing of basal segments called "tako-tsubo cardiomyopathy".
      METHODS: After obtaining institutional review board approval, the authors
      retrospectively identified among all patients admitted to the Mayo Clinic's
      Neurological Intensive Care Unit between January 1990 and January 2005 those with
      aneurysmal SAH who had met the echocardiographic criteria for tako-tsubo
      cardiomyopathy. Among 24 patients with SAH-induced reversible cardiac
      dysfunction, the authors identified eight with SAH-induced tako-tsubo
      cardiomyopathy. All eight patients were women with a mean age of 55.5 years
      (range 38.6-71.1). Seven patients presented with a poor-grade SAH, reflected by a
      Hunt and Hess grade of III or IV. Four patients underwent aneurysm clip
      application, and four underwent endovascular coil occlusion. The initial mean
      ejection fraction (EF) was 38% (range 25-55%), and the mean EF at recovery was
      55% (range 40-68%). Cerebral vasospasm developed in six patients, but cerebral
      infarction developed in only three patients. CONCLUSIONS: The authors describe
      the largest cohort with aneurysmal SAH-induced tako-tsubo cardiomyopathy. In the
      SAH population, tako-tsubo cardiomyopathy predominates in postmenopausal women
      and is often associated with pulmonary edema, prolonged intubation, and cerebral
      vasospasm. Additional studies are warranted to understand the complex mechanism
      involved in tako-tsubo cardiomyopathy and its intriguing relationship to
      neurogenic stunned myocardium.

PMID- 17219833
TI  - Endoscopic resection of solid intraventricular brain tumors.
AB  - OBJECT: Endoscopic removal of intraventricular brain tumors is well established
      for cystic tumors such as colloid cysts. Aspiration followed by removal or
      ablation of the membranous wall is possible given the constituent features of
      these tumors. It is generally expected that endoscopic removal of solid brain
      tumors from the intraventricular compartment would impose additional technical
      demands. In this paper, the feasibility and safety of endoscopic removal of solid
      intraventricular brain tumors is evaluated. METHODS: Eighty-one patients who
      underwent endoscopic management of an intraventricular brain tumor were
      identified from a prospective database. Of these patients, seven underwent
      attempted endoscopic surgical removal of a solid primary brain tumor. Patient
      selection, surgical technique, procedure-related morbidity, and extent of removal
      were reviewed. Five patients underwent complete resection of a solid
      intraventricular brain tumor, a treatment option that was based on intraoperative
      assessment and confirmed by postoperative imaging. No patient experienced any
      procedure-related morbidity. Of the individuals in whom a total endoscopic
      resection was successful, there has been no symptomatic or radiological evidence
      of recurrence (mean follow up 20 months). Maximum tumor diameter ranged from 0.5
      to 1.8 cm for patients who underwent complete resection, whereas maximum tumor
      diameter measured 2.4 and 2.5 cm in the two patients in whom a subtotal excision
      was performed. CONCLUSIONS: In select patients, complete endoscopic removal of
      solid intraventricular brain tumors is possible and safe. Factors that influence
      the ability of a surgeon to perform a complete endoscopic resection include tumor
      size, composition, and vascularity. The procedure requires careful patient
      selection, the use of refined endoscopic instrumentation, and a disciplined
      surgical technique.

PMID- 17219834
TI  - Three-tesla magnetic resonance imaging of the ventrolateral thalamus: a
      correlative anatomical description.
AB  - OBJECT: Surgery for tremor targets the ventrolateral nuclei of the thalamus. An
      initial radiological estimation of this target can be further refined through
      intraoperative physiological confirmation. Direct visualization of these nuclei
      has not yet been described. The improved signal-to-noise ratio associated with 3
      tesla (3T) magnetic resonance (MR) imaging makes increased spatial resolution
      possible, which may aid in the identification of subtle morphological features.
      This study was conducted to describe the anatomy of the nuclei and fiber
      projections within the ventral thalamus by using 3T MR imaging. METHODS: Using a
      commercially available 3T MR unit, the authors obtained images of a formalin
      fixed, paraffin-embedded brain. Slices with a 2-mm thickness and 0.2-mm gap were
      obtained parallel to the anterior commissure-posterior commissure (AC-PC) line.
      The brain was then sectioned through the cerebral hemispheres to obtain tissue
      slices encompassing the same levels. Adjacent 10-microm paraffin sections from
      the middle of each level were stained with Luxol fast blue and cresyl violet. The
      MR image and histological sections at the level of the AC-PC line were then
      compared in detail. In a separate study, the human thalamus was scanned in vivo
      using 3T and 1.5T MR imaging for anatomical comparison. CONCLUSIONS: The anatomy
      of the nuclei and fiber projections within the ventrolateral thalamus in humans
      can be described using 3T MR imaging. The findings were reproducible in vivo with
      3T but not 1.5T MR imaging. Additional studies are needed to confirm the accuracy
      of this observation for clinical purposes.

PMID- 17219835
TI  - Effect of subthalamic nucleus lesions in a 6-hydroxydopamine-induced rat
      parkinsonian model: behavioral and biochemical studies.
AB  - OBJECT: The purpose of this study was to determine whether subthalamic nucleus
      (STN) ablation caused by kainic acid can restore dopaminergic neurotransmission
      and improve motor deficits in a 6-hydroxydopamine (6-OHDA)-induced
      hemiparkinsonian model. METHODS: The authors investigated behavioral changes in
      rats displaying parkinsonian symptoms (6-OHDA-lesioned rats) after an STN lesion
      was created using kainic acid. They also measured levels of dopamine and its
      metabolites following tissue dissection. The results of this study showed that
      STN ablation led to behavioral improvement in parkinsonian motor deficits.
      Increased levels of dopamine were also observed in the striatum and globus
      pallidus externus (GPE). CONCLUSIONS: The results indicate that creation of an
      STN lesion in this hemiparkinsonian rat model may counteract some of the
      neurochemical changes within the striatum and GPE caused by the 6-OHDA, and
      influence striatal dopaminergic metabolism.

PMID- 17219836
TI  - Involvement of phospholipase C in endothelin 1-induced stimulation of Ca++
      channels and basilar artery contraction in rabbits.
AB  - OBJECT: Endothelin 1 (ET-1) is a major cause of cerebral vasospasm after
      subarachnoid hemorrhage (SAH), and extracellular Cal++ influx plays an essential
      role in ET-1-induced vasospasm. The authors recently demonstrated that ET-1
      activates two types of Ca"-permeable nonselective cation channels (designated
      NSCC-1 and NSCC-2) and a store-operated Cal++ channel (SOCC) in vascular smooth
      muscle cells located in the basilar arteries (BAs) of rabbits. In the present
      study, they investigate the effects of phospholipase C (PLC) on ET-1-induced
      activation of these Ca++ channels and BA contraction by using the PLC inhibitor
      U73122. Methods. To determine which Cal++ channels are activated via a PLC
      dependent pathway, these investigators monitored the intracellular free Cal++
      concentration ([Ca++]i). The role of PLC in ET-1-induced vascular contraction was
      examined by performing a tension study of rabbit BA rings. The U73122 inhibited
      the ET-1-induced transient increase in [Ca++]i, which resulted from mobilization
      of Ca++ from the intracellular store. Phospholipase C also inhibited ET-1-induced
      extracellular Ca++ influx through the SOCC and NSCC-2, but not through the NSCC
      1. The U73122 inhibited the ET-1-induced contraction of the rabbit BA rings,
      which depended on extracellular Cal++ influx through the SOCC and NSCC-2.
      Conclusions. These results indicate the following. (1) The SOCC and NSCC-2 are
      stimulated by ET-1 via a PLC-dependent cascade whereas NSCC-1 is stimulated via a
      PLC-independent cascade. (2) The PLC is involved in the ET-1-induced contraction
      of rabbit BA rings, which depends on extracellular Ca++ influx through the SOCC
      and NSCC-2.

PMID- 17219837
TI  - Optic radiations: a microsurgical anatomical study.
AB  - OBJECT: In this study, the authors used a fiber-dissection technique to describe
      the optic radiation. They focused on the morphological characteristics (length
      and breadth) of this structure, its course, and its relationships with
      neighboring fasciculi and the lateral ventricle. METHODS: The authors dissected
      10 previously frozen, formalin-fixed human brains with the aid of an operating
      microscope by following the fiber dissection technique described by Klingler in
      1960. Lateral, inferior, and medial approaches were made. The optic radiation,
      also known as the Gratiolet radiation, extended from the lateral geniculate body
      to the calcarine fissure. The average distance from the tip of the anterior Meyer
      loop to the calcarine sulcus was 105 mm (range 95-114 mm). The breadth of the
      optic radiations, one on each side of the brain, averaged 17 mm at the level of
      the inferior horn (range 15-18 mm). This tract could be divided into three main
      segments: the anterior or Meyer loop, the body, and the end of the optic
      radiation. Adjacent anatomical structures included: laterally, the inferior
      longitudinal fasciculi; medially, the tapetum of the corpus callosum; and the
      ependyma of the inferior horn of the lateral ventricle. CONCLUSIONS: Various
      practical surgical approaches are discussed. The knowledge gained by studying
      this particular anatomy will help prevent injury to the optic radiations during
      neurosurgery.

PMID- 17219838
TI  - Anatomical analysis of transoral surgical approaches to the clivus.
AB  - OBJECT: The authors conducted a cadaveric anatomical study to quantify and
      compare the area of surgical exposure and the freedom available for instrument
      manipulation provided by the following four surgical approaches to the
      extracranial periclival region: simple transoral (STO), transoral with a palate
      split (TOPS), Le Fort I osteotomy (LFO), and median labioglossomandibulotomy
      (MLM). METHODS: Twelve unembalmed cadaveric heads with normal mouth opening
      capacity were serially dissected. For each approach, quantitation of extracranial
      periclival exposure and freedom for instrument manipulation (known here as
      surgical freedom) was accomplished by stereotactic localization. To quantify the
      extent of extracranial clival exposure obtained, anatomical measurements of the
      extracranial clivus were performed on 17 dry skull bases. The values (means +/-
      standard deviations in mm2) for periclival exposure and surgical freedom,
      respectively, for the surgical approaches studied were as follows: STO = 492 +/-
      229 and 3164 +/- 1900; TOPS = 743 +/- 319 and 3478 +/- 2363; LFO = 689 +/- 248
      and 2760 +/- 1922; and MLM 1312 +/- 384 and 8074 +/- 6451. The extent of linear
      midline clival exposure and the percentage of linear midline clival exposure
      relative to the total linear midline exposure were as follows, respectively: STO
      = 0.6 +/- 4.9 mm and 7.8 +/- 11%; TOPS = 8.9 +/- 5.5 mm and 24.2 +/- 16.7%; LFO =
      32.9 +/- 10.2 mm and 85.0 +/- 18.7%; and MLM = 2.1 +/- 4.4 mm and 6.7 +/- 11.1%.
      CONCLUSIONS: The choice of approach and the resulting degree of complexity and
      associated morbidity depends on the location of the pathological entity. The
      authors found that the MLM approach, like the STO approach, provided good
      exposure of the craniocervical junction but limited exposure of the clivus. The
      TOPS approach, an approach attended by a lesser risk of morbidity, provided
      adequate exposure of the extracranial inferior clivus. Maximal exposure of the
      extracranial clivus proper was provided by the LFO approach.

PMID- 17219839
TI  - Concurrent lymphocytic hypophysitis and pituitary adenoma. Case report and review
      of the literature.
AB  - Lymphocytic hypophysitis (LyH) is an uncommon intrasellar lesion characterized by
      lymphocytic infiltration of the adenohypophysis. Evidence suggests that the cause
      is autoimmune, and the symptoms are usually related to either a mass effect or
      endocrine dysfunction. Lymphocytic hypophysitis has been described rarely in the
      setting of other simultaneous pathological processes that involve the pituitary
      and sella turcica, and is postulated to arise from an intrinsic inflammatory
      response. The authors report the case of a 43-year-old woman who presented with a
      2-month history of galactorrhea and pseudohyperprolactinemia secondary to a 10-mm
      lesion within an enlarged pituitary gland. She was nulliparous and had no
      contributory medical history. Serial neuroimaging performed over a 2-year period
      demonstrated lesion growth, and visual deficits had developed; together these
      warranted surgical intervention. A transsphenoidal resection was performed.
      Microscopic and immunohistopathological examinations revealed a nonsecreting
      pituitary adenoma with concurrent lymphocytic adenohypophysitis. This is the
      first documented case of LyH in the setting of a null-cell pituitary adenoma. The
      authors review the related literature and outline potential mechanisms for the
      concurrent development of LyH and a pituitary adenoma.

PMID- 17219840
TI  - Subdural hemorrhage in the posterior fossa caused by a ruptured cavernous carotid
      artery aneurysm after a balloon occlusion test. Case report.
AB  - Given the relatively benign natural history of cavernous carotid artery aneurysms
      and based on anecdotal reports in the literature of subarachnoid hemorrhage (SAH)
      or subdural hemorrhage (SDH) from these aneurysms, observation is warranted and
      typically recommended. In this case report, the authors describe a woman who
      harbored a partially thrombosed, giant cavernous aneurysm that ruptured after she
      underwent a balloon occlusion test (BOT) and predominately led to an SDH. The
      authors believe that this occurrence is the first such report in the English
      literature. They discuss possible mechanisms for this event and the literature
      related to SAH or SDH from cavernous aneurysms, including why cavernous aneurysms
      cause such hemorrhages. The authors also recommend that attention be paid to such
      lesions regarding the possibility of aneurysmal rupture following a BOT.

PMID- 17219841
TI  - Spontaneous bacterial peritonitis causing Serratia marcescens and Proteus
      mirabilis ventriculoperitoneal shunt infection. Case report.
AB  - The authors report their experience treating a polymicrobial ventriculoperitoneal
      (VP) shunt infection in a developmentally delayed 21-year-old woman.
      Cerebrospinal fluid (CSF) cultures grew Serratia marcescens and Proteus
      mirabilis. On admission and throughout her hospitalization, results of physical
      examination of her abdomen were normal, and radiographic studies showed no
      evidence of bowel perforation or pseudocyst formation. Contrast-enhanced computed
      tomography of the abdomen revealed a small fluid collection. After a course of
      intravenous gentamicin and imipenem with cilastatin in conjunction with
      intrathecal gentamicin, the infection was resolved and the VP shunt was
      reimplanted. Although VP shunt infections are not uncommon, S. marcescens as a
      causative agent is exceedingly rare and potentially devastating. Only two
      previous cases of S. marcescens shunt infection have been reported in the
      literature. Authors reporting on S. marcescens infections in the central nervous
      system (CNS) have observed significant morbidity and death. Although more common,
      the presence of P. mirabilis in the CSF is still rare and highly suggestive of
      bowel perforation, which was absent in this patient. Spontaneous bacterial
      peritonitis was the likely source from which these bacteria gained entrance into
      the VP shunt system, eventually causing ventriculitis in this patient. The
      authors conclude that in light of the high morbidity associated with S.
      marcescens infection of the CNS, intrathecal administration of gentamicin should
      be strongly considered as part of first-line therapy for S. marcescens infections
      in VP shunts.

PMID- 17219842
TI  - Gamma knife surgery-induced meningioma. Report of two cases and review of the
      literature.
AB  - Gamma Knife surgery (GKS) is a minimally invasive neurosurgical technique. During
      the past 30 years, radiosurgery has been performed for a number of intracranial
      disorders with a generally low incidence of side effects. Although radiation
      induced neoplasia following radiotherapy is well documented, there are few
      reports of this complication following radiosurgery. The authors are engaged in
      an ongoing project in which they are studying the delayed adverse effects of
      radiosurgical changes in 2500 patients with arteriovenous malformations (AVMs)
      treated within a 30-year period. The cases of 1333 patients treated by the senior
      author (L.S.) have been reviewed thus far. A subset of 288 patients in this group
      underwent neuroimaging and participated in clinical follow up for at least 10
      years. The authors report two cases of radiosurgically induced neoplasia. In both
      cases the patient was treated with GKS for an AVM. Longer than 10 years after
      GKS, each of the patients was found to have an incidental, uniformly enhancing,
      dura-based mass lesion near the site of the AVM. These lesions displayed the
      imaging characteristics of a meningioma. Because in both cases the lesion has
      displayed no evidence of a mass effect, they continue to be followed using serial
      neuroimaging. These are the fifth and sixth cases meeting the criteria for
      radiation-induced neoplasms defined by Cahan, et al., in 1998. Although
      radiosurgery is generally considered quite safe, the incidence of radiation
      induced neoplasms is not known. These cases and the few others detailed in the
      literature emphasize the need for long-term neurosurgical follow-up review in
      patients after radiosurgery.

PMID- 17219843
TI  - Primary cerebellopontine angle craniopharyngioma in a patient with gardner
      syndrome. Case report and review of the literature.
AB  - The authors report on the case of a craniopharyngioma arising in the
      cerebellopontine angle (CPA) in a patient with Gardner syndrome. Although
      familial adenomatous polyposis (FAP) is associated with intracranial neoplasms,
      the current case is only the third reported craniopharyngioma in a patient with
      Gardner syndrome. Two of these tumors, including that of the current case,
      originated in the CPA, an unusual location for craniopharyngiomas. The literature
      concerning FAP and its associations with intracranial neoplasia, as well as the
      pathogenesis of craniopharyngiomas in the posterior fossa, is discussed.

PMID- 17219844
TI  - Transpetrosal approach.

PMID- 17219845
TI  - Intracerebral hemorrhage.

PMID- 17219846
TI  - Chronic brain ischemia and revascularization.

PMID- 17219847
TI  - Parasitic infections and maternal awareness of preschool children in Karmouz
      district, Alexandria.
AB  - Intestinal parasitic infections are widespread especially among preschool
      children living in poor areas. Also pediculosis has been perceived as a public
      health nuisance for decades. A cross-sectional study was conducted on 256
      children and their mothers in a poor urban district to assess mothers' knowledge
      and practices as regards parasitic infections and infestations that may be
      present in her preschool child, and to correlate the presence of these infections
      with her awareness. A pre-designed questionnaire that included socio-demographic
      data, items to assess mothers' knowledge of sources and preventive measures of
      parasitic infections and infestations and her practices was completed. A stool
      sample was collected from children and examined using formol-ether technique and
      Sellotape technique was used to detect Enterobius vermicularis. Pediculus capitis
      was diagnosed by inspection of the scalp and was found to be the most prevalent
      parasite found in 58.9% of those children followed by Enterobius vermicularis in
      46%. A strong positive association between pediculosis and enterobiasis was
      detected (phi coefficient = 0.956, p < 0.001). Socioeconomic level affected both
      knowledge and practices scores where one point change in knowledge score or
      socioeconomic score caused an increase in practice score of 0.279 and 0.071,
      respectively. Also higher risk of pediculosis was found to be significantly
      associated with female sex and low socioeconomic level. An increase of one point
      in practice score showed a decrease in the log likelihood ratio of enterobiasis
      of 14.3%. The majority of mothers (77.3%) were found to be aware that their
      children had a parasitic infection, which was significantly associated with
      results of stool analysis. This indicates that awareness building is not enough
      to be of practical benefit. Appropriate and detailed control methods of parasitic
      infections and pediculosis must be taught and applied by parents and community.
      Socio-economic development, organized health programs and motivation should be
      undertaken to help today's children.

PMID- 17219848
TI  - Premarital counseling: view of the target group.
AB  - Premarital counseling is one of the most important strategies for prevention of
      genetic disorders, congenital anomalies and several medical, psychosocial marital
      problems. Nursing students as a target group are in a unique position to provide
      prospective couples with information and guidance regarding premarital
      counseling. The aim of this study is to assess knowledge and attitude of
      secondary technical nursing school students towards premarital counseling in
      Alexandria. The study was conducted at four secondary technical nursing schools.
      200 students from the chosen schools participated in the study. Questionnaire
      sheet was developed to assess student's knowledge and a 3-point Likert-like scale
      was used to assess the student's attitude. The results revealed that 46.5% of the
      study sample had an average score in knowledge, while 65.5% of the students had a
      positive attitude towards premarital counseling. The recommendations focused on
      dissemination of information through formal and informal education and media
      publicity.

PMID- 17219849
TI  - Solidification as low cost technology prior to land filling of industrial
      hazardous waste sludge.
AB  - The aim of this study is to stabilize and solidify two different treated
      industrial hazardous waste sludges, which were selected from factories situated
      close to Alexandria. They were selected to ensure their safe transportation and
      landfill disposal by reducing their potential leaching of hazardous elements,
      which represent significant threat to the environment, especially the quality of
      underground water. The selected waste sludges have been characterized. Ordinary
      Portland Cement (OPC), Cement Kiln Dust (CKD) from Alexandria Portland Cement
      Company, and Calcium Sulphate as a by-product from the dye industry were used as
      potential solidification additives to treat the selected treated waste sludges
      from tanning and dyes industry. Waste sludges as well as the solidified wastes
      have been leach-tested, using the General Acid Neutralization Capacity (GANC)
      procedure. Concentration of concerning metals in the leachates was determined to
      assess changes in the mobility of major contaminants. The treated tannery waste
      sludge has an acid neutralization capacity much higher than that of the treated
      dyes waste sludge. Experiment results demonstrated the industrial waste sludge
      solidification mix designs, and presented the reduction of contaminant leaching
      from two types of waste sludges. The main advantages of solidification are that
      it is simple and low cost processing which includes readily available low cost
      solidification additives that will convert industrial hazardous waste sludges
      into inert materials.

PMID- 17219850
TI  - Effect of occupational lead-exposure on blood pressure, serum aldosterone level
      and plasma renin activity.
AB  - Numerous observations have indicated a relationship between lead exposure and
      elevated blood pressure. The present study aims to investigate the association
      between occupational lead-exposure and elevated blood pressure as well as serum
      aldosterone level and plasma renin activity as parameters affecting blood
      pressure. Fifty occupationally lead-exposed (16 males and 34 females) and 50 non
      exposed (15 males and 34 females) workers were selected after application of
      certain exclusion criteria. All workers were admitted to complete clinical
      examination, including standard blood pressure measurement. Also, blood lead
      level, serum aldosterone concentration and plasma renin activity were estimated.
      The results of both occupationally lead-exposed males and females demonstrated no
      significant differences regarding age, work duration, systolic and diastolic
      blood pressures when compared to occupationally non-exposed males and females;
      respectively. In addition, occupationally lead-exposed males and females revealed
      a significant increase in blood lead level and serum aldosterone concentration in
      comparison to their controls. Moreover, plasma renin activity is significantly
      decreased among the lead-exposed male workers while it is significantly increased
      among the lead-exposed female workers in comparison to their controls. It is
      concluded that serum aldosterone level and plasma renin activity are affected by
      occupationally low-level of lead exposure, and the present study provide further
      support for the association between blood lead exposure and blood pressure
      related hormones.

PMID- 17219851
TI  - Discriminant analysis of free fatty acids of some Egyptian snails as a step for
      schistosomiasis control: new trends.
AB  - Schistosomiasis is still the most common occupational health problem of rural
      workers in Egypt. The use of molluscicides, either chemical or biological, and
      environmental changing are the most successful methods of snail control. The new
      trend in Schistosoma control programs is to study the ecological factors that
      attract miracidium Schistosoma specific snails, to emphasizing to find out new
      environmental safe control methods. Since Schistosoma worms do not make fatty
      acids de novo, they require host lipids for survival and to complete their life
      cycle. Discriminate analysis of the estimated free fatty acids was done in this
      study in Biomphalaria alexandrina, Biomphalaria glabrata, and Bulinus truncatus,
      viz. Lymnaea truncatula and Physa acuta (Schistosoma intermediate and non
      intermediate respectively). With the objective of determination of the
      biochemical difference that attract the infestation of Schistosoma miracidium to
      the target snails, as a step of the new control trends. Caprylic acid (C8:0), and
      Oleic acid (C18:1) are significantly lower in the tissues of Schistosoma
      intermediate snails compared to the non-intermediate snails. While, Capric acid
      (C10:0), Margaric acid (C17:0), and Lenoleic acid (C18:2) of the intermediate
      snails are significantly higher than that of non-intermediate snails. The percent
      of correct medical classification of snails are more than 80% according to
      Caprylic acid, Margaric acid, and Lenoleic acid, the other 15 fatty acids are
      less than 80%. These three free fatty acids could be chemoattractive of
      Schistosoma miracidium, and could be used as safe environmental control
      compounds, which needs further research.

PMID- 17219852
TI  - Some epidemiological aspects of patients with end stage renal diseases.
AB  - This study was carried out to describe End Stage Renal Disease (ESRD) among
      Egyptian patients and to identify the possible risk factors of their disease. A
      case-control study was conducted with 2 control groups (patient or hospital
      control group and normal community control group) compared with ESRD cases on
      haemodialysis. The study revealed that hypertension, followed by obstructive
      uropathy, are the leading causes of ESRD. Conducting the multiple logistic
      regression analysis, the following factors were found to act independently as
      risk factors for ESRD, in that order of importance: past history of hypertension,
      family history of renal failure, past history of renal pain, smoking, urban
      origin of birth, past history of renal or urinary stones, past history of
      schistosomiasis, the presence of a near-by residential factory and past history
      of frequent hospitalization. A quality of life score has been invented. Women
      experienced a bad quality of life in relation to men and the score correlated
      positively with age. A number of recommendations have been generated.

PMID- 17219853
TI  - Comparison between aerobic and anaerobic co-composting of agricultural residues.
AB  - Fertile soil is the most important resource for food production. The agricultural
      area in Egypt is limited to 6 million faddans. This limited area has derived many
      farmers to use several types of chemical fertilizers, to enhance the fertility of
      the land and hence the productivity. Excessive application of chemical fertilizer
      lead to the build up of these residuals because they are superfluous. This will
      cause waste of money and also soil pollution. Ultimately, this would adversely
      affect the ecological system in the soil and surrounding environment, especially
      water bodies. Composting of organic solid wastes will address some of the
      problems of solid waste disposal and gives a beneficial product which may replace
      the expensive chemical fertilizers. Other organic compostable solid wastes could
      be utilized to produce this compost. Agricultural residues are cheap raw
      materials for such compost and are available in vast quantities as well. This
      compost can be used as a soil conditioner to improve soil characteristics and its
      productivity. Crop residues mixed with manure, may be co-composted to give a soil
      conditioner. Agricultural residues, about 106 million tons/year, may produce
      about 55 million tons/year of compost. Three co-composting were carried out at
      the experimental station of the Faculty of Agriculture in Abis. Two aerobic co
      composting of winter and summer crop residues and one anaerobic co-composting
      inter rop esidue were produced. The development of the co-composting processes
      controlled by the temperature, moisture content, and chemical composition was
      studied. The aerobic co-composting of winter crop residues was found to be the
      best experiment as it complied with the standards of the Ministry of Agriculture
      Decree No. 100/1967. This co-compost is expected to be free from pathogenic
      microorganisms as the dominant temperature was almost about 50 degrees C from the
      42nd day till the 101st day of the experiment.

PMID- 17219854
TI  - Sociodemographic determinations of management behavior of diabetic patients
      attending a diabetic clinic in Alexandria. Part III: Relation between diabetics'
      sociodemographic background and health belief model variables.
AB  - The present work aims to study the relation between patient's health beliefs and
      psychological perception and demographic variables. The same subjects and methods
      applied in part I and II was adopted. It was found that a minority (1.7%) had a
      weak overall perceived susceptibility. However the rest were categorized as
      having either moderate (36.3%) or strong perception (62.0%). None of the diabetic
      patients was graded as having a weak overall perceived severity level. The
      remaining diabetics were graded as having either moderate (50.7%) or strong
      perception (49.3%). The majority (98.3%) had a strong perception and the rest had
      a moderate one. None of diabetic patients had weak overall internal cues to
      action towards their health. They had either moderate (59.7%) or strong cues
      (40.3%). Age of diabetic patients was linearly associated with the overall
      perceived severity level (X2 (MH) = 10.49). The younger the patients the more
      likely that they were classified as having a strong perception. Moreover, a
      significant linear association was observed between age and exposure to external
      cues to action (X2(MH) = 8.17), where the older the patients the more likely that
      they were exposed to external cues to action. It was observed that a significant
      relation was observed between gender and exposure to external cues to action (X2
      = 4.60), where females were more likely to be exposed than males to external cues
      to action. A statistical significant linear association was observed between the
      education of diabetics and exposure to external cues to action (X2(MH) = 9.26).
      Diabetics without any educational certificates were more likely to be exposed to
      external cues to action. The present study provides data on the level of
      perception of diabetic patients in order to plan for a diabetic education
      programme.

PMID- 17219855
TI  - Anxiety among school age children suffering from asthma.
AB  - The aim of the present work was to study anxiety among school age students
      suffering from asthma. The study was conducted on a total number of 146 asthmatic
      preparatory school students, attending the asthma clinic in Sporting Students'
      Hospital in Alexandria Governorate. The study was performed during the period
      from June to September 1997. A matching control of 223 non-asthmatic students
      from the preparatory school in the East educational zone in Alexandria
      Governorate were also included in the study. The study was carried out through a
      cross-sectional approach. A structured self-administered questionnaire was used
      to collect data about, the general characteristics of the sample, interpersonal
      and inter-parental relationships, school performance and the attitude and
      behavior of mothers towards their asthmatic children. The Arabic version of State
      Trait Anxiety Inventory (STAI) was used to identify children with anxiety state.
      The present result revealed that 24.7% of the asthmatic students were anxious,
      with a higher preponderance among boys than girls (26.6%, 21.2%, respectively).
      Bad interpersonal and inter-parental relationships had increased the risk of
      occurrence of anxiety state among asthmatic children. Also, poor scholastic
      achievement was more encountered among asthmatics who had anxiety. The
      development of asthma education programs to increase parents', children's and
      teachers' awareness of asthma symptoms and asthma trigger events was recommended.

PMID- 17219856
TI  - Study of nosocomial respiratory infections and nurses' performance related to
      infection control measures in artificially ventilated patients.
AB  - The aim of this study was to assess nurses' performance related to control and
      prevention of nosocomial respiratory infection in artificially ventilated
      patients and to estimate incidence and the causative microorganisms of such
      infection. The study was conducted on 30 ventilated patients and 30 nurses who
      were responsible for their care. An observation checklist was used to assess
      nurses' practices regarding daily care activities, ventilator decontamination,
      use of universal infection control measures and maintenance of the patients' care
      environment. A second sheet was developed to estimate incidence of nosocomial
      respiratory infection and identification of the causative microorganisms. A third
      sheet was designed to help in daily assessment of the patient's health condition.
      The study revealed a high incidence of nosocomial respiratory infections (83.3%)
      and pseudomonas was the causative agents in more than one-fourth of the cases.
      Moreover, nurses' infection control practices were inadequate.

PMID- 17219857
TI  - Examination for hepatitis E virus in wastewater treatment plants and workers by
      nested RT-PCR and ELISA.
AB  - Water and sera were collected from 4 sewage treatment plants whose workers were
      exposed to raw untreated sewage samples, which may accumulate the HEV virus. Two
      methods of water concentration were used (PEG and U-APB) and samples analyzed by
      nested RT-PCR. The 24 samples (inlet and outlet) of sewage treatment plants were
      negative for virus. HEV IgG was detected in 205 workers sera, the age of 20-40
      years old, exhibited the highest HEV IgG infection (50.9% - 50.4), between 41-50
      and 51-60 years old were lower and almost the same (43.2%, 46.2%, respectively).
      The highest infections between workers were in Balaks sewage treatment plant, and
      the persistence of HEV IgG was until 60 years old.

PMID- 17219858
TI  - Intestinal tuberculosis in patients with fever of unknown origin in Egypt.
AB  - Nineteen patients with intestinal tuberculosis were admitted to the Abbassia
      Fever Hospital in the period 1991-1997. Fever, abdominal pain, diarrhea, and
      weight loss were the most common symptoms. Small bowel radiology and colonoscopy
      were helpful in establishing the diagnosis. The difficulties in diagnosing
      tuberculous enteritis and the need to consider seriously the possibility of this
      disease in such patients is most important and is discussed.

PMID- 17219859
TI  - Extra-pulmonary tuberculosis in patients with fever of unknown origin: clinical
      features and diagnosis.
AB  - One hundred twenty-nine patients with extra-pulmonary tuberculosis admitted at
      the Abbassia Fever Hospital, NAMRU-3 during a seven year period (1991 to 1997)
      are described. Tuberculous peritonitis was diagnosed in 35 patients, tuberculous
      lymphadenitis in 32, intestinal tuberculosis in 19, genito-urinary tuberculosis
      in 14, skeletal tuberculosis in 13, disseminated miliary tuberculosis in 11, and
      splenic tuberculosis in 5 patients. The clinical picture included fever, and
      weight loss accompanied by anaemia and an elevated erythrocyte sedimentation rate
      in all patients.

PMID- 17219861
TI  - A study of pattern of gastrointestinal malignant neoplasms in the last decade
      (1987-1996) in Alexandria.
AB  - The present study was conducted to reveal the pattern of different
      gastrointestinal malignant neoplasms in Alexandria in the last decade (1987
      1996). All registered cases of GIT cancers in Alexandria. Main University
      Hospital in the last decade were included in the study. The results revealed that
      the total number of cases was 2184, 58.6% were males and 41.4% were females. The
      mean age of registered cases was significantly older among males than females (t
      = 2.43). The highest percentage (47.2%) of cases were in the age group (40- < 60
      years). Less than quarters (73.3%) of the total cases have had malignant
      neoplasms of digestive organs and 26.7% have had malignant neoplasms of lips,
      oral cavity and pharynx. Of the latter category cancer pharynx came first in both
      sexes (49.9%) with the youngest mean age (45.65 +/- 15.79 years), followed by
      cancer tongue (24.9%) with the oldest mean age (58.56 +/- 12.4). Among cases of
      malignant neoplasms of digestive organs, cancer colon came first in both sexes
      (26.9%) with the youngest mean age (44.11 +/- 14.08 years). Cancer gall bladder
      came last (1.2%) with the oldest mean age (55.80 +/- 10.20 years). Over the last
      decade trend of malignant neoplasms of colon, rectum, liver and pancreas were
      increasing while the reverse was observed for cancer oesophagus and stomach. So
      it is necessary to plan for GIT cancer control programme.

PMID- 17219860
TI  - Chromium induced contact dermatitis and indices for diagnosis.
AB  - Chromium exposure plays an important role in development of contact dermatitis.
      The prevalence of contact dermatitis among tannery workers and cement-exposed
      workers is high. This study was designed to determine the prevalence of contact
      dermatitis among some Egyptian workers exposed to chromium and to investigate the
      role of patch test and IgE immunoassay in diagnosis of contact dermatitis. Eighty
      three male workers who were exposed to chromium were selected after application
      of certain exclusion criteria to be the target population of this study. Forty
      male workers away from exposure to chromium were taken to be the controls. All
      the exposed and non exposed workers were investigated through an interview
      questionnaire, clinical examination, patch test and determination of blood and
      urine chromium levels, absolute eosinophilic count and total IgE level. The
      results showed that there was no significant difference between exposed workers
      with clinically diagnosed contact dermatitis and the clinically free exposed
      workers regarding age and work duration. 7.7% of exposed workers with positive
      patch test suffered from contact dermatitis while 31.6% of exposed workers with
      negative patch test suffered from contact dermatitis. There was no statistically
      significant difference between clinically diagnosed contact dermatitis workers
      and clinically free workers regarding blood and urine chromium levels. IgE level
      and absolute eosinophilic count were statistically higher among exposed workers
      with contact dermatitis than among clinically free exposed workers. According to
      the results of this study, it is concluded that the diagnosis of skin
      hypersensitivity to chromium should depend upon the history of chromium exposure,
      clinical examination and a battery of investigations including IgE level,
      eosinophilic count and patch test.

PMID- 17219862
TI  - Prevalence of juvenile chronic arthritis in school children aged 10 to 15 years
      in Alexandria.
AB  - The study was conducted using a cross sectional design to determine the
      prevalence of Juvenile chronic arthritis (JCA) among 10 to 15 years old school
      children in Alexandria, and to develop (if possible) a tool for screening
      children for arthritis. The study included 1500 children selected by using a
      multistage stratified random sample of students enrolled in the primary and
      preparatory schools in Alexandria Governorate. The results of this study
      indicated that the prevalence of JCA was 3.3 per 1000. Also a simple tool,
      composed of some questions, could effectively identify children with JCA.
      However, clinical examination supported by a history from the child provides the
      best reliable means of diagnosis. The present study recommended the use of
      community rather than hospital based surveys for estimating the true prevalence
      of the disease.

PMID- 17219863
TI  - Breast cancer in relation to some reproductive factors.
AB  - Breast cancer is one of the most commonly occurring cancers in females in the
      Eastern Mediterranean Region. In Egypt women's breast cancer had the highest
      frequency. The present study was conducted to study the association between
      breast cancer and some reproductive factors as well as to find out (if possible)
      predictors for occurrence of breast cancer. A hospital based case control study
      was carried out in Alexandria Main University Hospital where, 129
      histopathologically confirmed incident primary breast cancer cases were included.
      An equal number of a control group matched by age were selected from the visitors
      of the same hospital. Data related to women's reproductive period were collected
      from both cases and controls. The results revealed that there was no
      statistically significant difference between cases and controls as regards
      menopausal status, menstruation span, number of births, spontaneous and induced
      abortion, twin birth, breast feeding and use of oral contraceptives. There was an
      increasing risk of breast cancer, with the presence of positive family history of
      breast cancer decreasing age at menarche, increasing age at first full-term
      pregnancy, widening of the interval between menarche and first full-term
      pregnancy, increasing age at last full-term pregnancy and shortening of the
      interval since last birth. Multiple logistic regression analysis revealed that
      positive family history of breast cancer, young age at menarche, late age at last
      full-term pregnancy and wide inter-birth interval were significant predictors for
      occurrence of breast cancer. The results of the study pinpoint that conduction of
      public health education programmes focusing on the modifiable risk factors are
      required.

PMID- 17219864
TI  - Assessment of health and nutritional status of infants in relation to breast
      feeding practices in Karmouz area, Alexandria.
AB  - Infants are most precious part of nation's life. Infant health is a reflection of
      the health of the mother and it gives an indication of the health of the adult
      population of the future. The present work was designed to study the health and
      nutritional status of infants in Karmouz area in Alexandria as well as the effect
      of breast feeding practices on the health status of infants. Accordingly, a house
      to house survey was conducted through cluster sampling technique. The total
      sample amounted to 396 mothers and 409 infants. Data were collected about infants
      health status and their feeding practices. Weight and length were measured for
      all infants. Stool samples were collected and examined. The results revealed that
      55.3% of infants had acute respiratory tract infections (ARI); 16.4% had
      bronchitis and 4.9% had pneumonia, 44% of the infants suffered from diarrhea,
      13.2% were infected with parasites, Gardia lamblia was the most commonly found
      parasite (9.0%). High proportion of infants was found to be stunted (22.7%), 8.6%
      were wasted and 7.6% were underweight, 40.3% of mothers were in partial practice
      level. Infants below six months of age who received solid foods at three months
      or less had a significantly higher percentage of diarrhea (70.6%) compared to
      51.5% among those of late weaning (four months or later). The diarrhea was
      significantly more common among infants aged 12 - < 18 months with about two
      times of risk relative to those aged < 6 months. A significantly higher risk of
      diarrhea was found for infants of bottle--or complementary feeding (OR = 2.05,
      2.07 respectively, model X2 = 9.71, P < 0.01), in addition the protective effect
      of breast feeding persisted after adjustment of confounders by multiple logistic
      regression. High proportion of mothers (63.8%) continued to breast-feed their
      babies during diarrheal episodes. On the other hand breast-feeding was not
      significantly protective against the acute respiratory tract infection. Stunting
      of the infants increases rapidly with age from 12.6% among infants under six
      months to 30.4% among those aged from 9 - < 12 months. The percentage of stunted
      infants varied greatly by education of the mothers, it was doubled from 14.7%
      among those of mothers of high level of education to 28.9% of non educated
      mothers with a significant high risk of 2.31 times. The repeated attacks of
      diarrhea throughout the two years of life was still significantly associated with
      stunting even after adjustment of confounders by multiple logistic regression;,
      those with three attacks or more had about three times of risk relative to those
      without the disease (OR = 2.56, 95% CL = 1.12-5.81, model X2 = 19.03, P < 0.01).
      Health education program should be emphasized to all mothers to improve their
      knowledge and practice about breast-feeding and its importance in prevention of
      diarrhea.

PMID- 17219865
TI  - Do elderly clubs in Alexandria meet the needs of their consumers?
AB  - The rapid rise in the number of the independent elderly persons in the community
      has become a world-wide phenomenon. Recently, more attention has been devoted to
      community based programs for the elderly. One type of these programs offering
      multiple services is the elderly clubs. These clubs may provide health and
      physical care beside social interaction and peer group support for the
      independent elderly in the community. In Alexandria, elderly health and social
      care provided are not coping with the increasing numbers of the aged population
      and consequently with their needs and problems. So the aim of this study was to
      describe the health profile of the consumers of the elderly clubs in Alexandria
      and to determine the preferred activities needed by the consumers of the elderly
      clubs in Alexandria. To fulfil this aim, a sample of 163 elderly representing the
      consumers from all (five) elderly clubs in Alexandria were interviewed. The
      results revealed that almost one third (30.67%) of the elderly consumers had no
      health complaints, 35.58% had only one health complaint and 33.74% had more than
      one complaint. The most health complaints stated by the consumers were
      cardiovascular diseases/hypertension followed by diabetes mellitus then rheumatic
      diseases/arthritis. The results also revealed that all the elderly consumers had
      one or more minor signs and symptoms during the last six months of the interview.
      These signs and symptoms varied from amnesia, low concentration, constipation,
      dizziness and dyspepsia. The majority of the elderly consumers preferred the
      recreational trips and attending religious seminars/reading Quraan. Walking and
      checking on blood pressure were the most preferred activities mentioned by nearly
      half the consumers. The results of this study can be considered as a base line
      data to help policy makers in taking decisions during planning and providing the
      needed services to the elderly.

PMID- 17219866
TI  - The effects of a training program on knowledge, attitude and practice of the
      staff of primary health care centers towards growth monitoring: an intervention
      study.
AB  - This study was carried out aiming at assessing the effects of a training program
      on the knowledge, attitude and practices (KAP) of health care workers (HCWs) in
      primary health care centers (PHCCs) regarding growth monitoring (GM). It included
      148 health care workers (30 General Practitioners (GPs) and 118 nurses), from 17
      PHCCs in Jeddah city, Kingdom of Saudi Arabia (KSA). Tests on KAP were held
      before and six months following a training program on GM conducted by the
      investigators. Results showed significant improvements in the KAP of the trained
      health care workers after training, the 44 trained HCWs obtained higher mean
      comprehension score (7.9 +/- 1.2), higher mean practice score (11.6 +/- 3.0), and
      higher mean general scores (32.3 +/- 4.6) compared to the mean scores they
      obtained in the pre-test (5.7 +/- 1.5; 7.4 +/- 2.2 and 25.7 +/- 4.4,
      respectively). These differences were statistically significant (P < 0.001).
      However; the difference in the mean knowledge scores, before and after the GM
      training program was not significant. The training has also led to the
      disappearance of the significant knowledge gap between GPs and nurses. And also,
      the 44 trained HCWs had higher mean comprehension score (7.9 +/- 1.2), mean
      practice score (11.6 +/- 3.0), and mean general scores (32.3 +/- 4.6) compared to
      those among untrained group (controls) (6.3 +/- 2.1; 8.5 +/- 3.7, and 27 +/- 6.1,
      respectively). These differences were statistically significant (P < 0.0005).
      Nevertheless, the difference in the mean knowledge scores, between the two
      groups, was not statistically significant. It also has led to some changes in the
      attitude of the trained HCWs towards GM compared to the untrained group. In
      conclusion, We credit the significant improvements in KAP of HCWs to the training
      program and recommend its adoption by the national MCH program in KSA. We also
      recommend new methods of teaching and training based on sound educational concept
      of active participation and practical work as well as supportive supervision and
      evaluation.

PMID- 17219867
TI  - RT-PCR and cell culture infectivity assay to detect enteroviruses during drinking
      water treatment processes.
AB  - In this study, 62 water samples were collected from two water treatment plants
      (WTPs) in Suez Canal cities (Port Said and Ismaillia) and one plant in Cairo
      (Giza WTP) in addition to the beginning of the two Nile river branches (Rosetta
      and Damietta). Viruses were concentrated by adsorption-elution ethod sing 142 mm
      diameter nitrocellulose membrane of 0.45 microm pore size and eluted with 3% beef
      extract at pH 9.5. The concentrated samples were inoculated for 3 successive
      passages in three cell culture types (Vero, BGM and RD). Enterovirus RNAs in CPE
      induced samples were extracted by guanidinium thiocyanate/ phenol/chloroform and
      heat shock methods and detected by RT-PCR and neutralization test. The results
      showed that eight samples [14.5% (8/62)] contained enteroviruses most of them
      were polioviruses [87.5% (7/8)] and coxsackievirus type B2 [12.5% (1/8)]. The
      three cell cultures were of the same sensitivity to detect the isolated viruses.
      Also, RT-PCR followed by neutralization assay facilitates and accelerate the
      results. The guanidinium thiocyanate extraction method was more sensitive than
      heat shock method. The results turned our attention to review our technology of
      water treatment and disinfection step in addition to the selection of suitable
      intake for the drinking water treatment plants.

PMID- 17219869
TI  - Bionomics of the anopheline vectors in an endemic area in Fayoum Governorate,
      Egypt.
AB  - A one-year longitudinal entomological study was carried out at Kafr Fazara
      village, Sinnuris District, Faiyoum Governorate from January to December 1996.
      The results revealed that three species of anophelines were found. A. sergenti
      was the most prevalent species followed by A. multicolor and the least prevalent
      one was A. pharoensis. The influence of climatic conditions on anopheline
      abundance was also studied. The mean monthly temperature has a significant effect
      on larvae abundance, while no significant correlation was found concerning
      relative humidity or wind speed for both larvae and adult anophelines. The
      transmission season of P. falciparum in Faiyoum Governorate extended to more than
      eight months a year which could explain the persistence of malaria up there. The
      bionomics of the recorded vectors were discussed.

PMID- 17219868
TI  - An outbreak of hepatitis A associated with treated waste water used for
      irrigation.
AB  - Hepatitis A virus (HAV) infection is endemic in developing countries and remains
      a public health problem elsewhere. This study was conducted to investigate an
      outbreak of HAV infection, which occurred during a period of almost 5 months
      (January-May 1996) in the National Guard Iskan (Housing Authority) in Jeddah,
      Saudi Arabia. Ninety four cases were found to be positive for IgM antibody to
      HAV. A case control study was done to identify possible risk factors. For every
      case, 3 controls have been selected from the same household matched for age and
      sex. Information about reported cases was obtained by attending physicians
      through an interview questionnaire from adult cases and parents of young cases
      and controls (<12 y). It included questions regarding symptoms, demographics and
      possible source of the infection. Results showed that the attack rate of the
      whole population was 1.03 %, while that for children <10 years was twofold higher
      (2.05 %) than the total population. The risk of acquiring infection among them
      was found to be five times that among those aged 40 years and higher (R.R=5.32).
      There was a lack of association between developing hepatitis A and any of the
      food items or milk used in the studied area during the time of the outbreak. On
      the other hand exposure to irrigation water among cases was found to be
      significantly higher than among controls especially among children below 10 years
      (O.R=2.26). Analysis of the available data suggests a strong association between
      illness and exposure to waste water used for irrigation of gardens through
      playing with it, or through occasional drinking especially among children below
      10 years. The prolonged course of the outbreak (5 months) may be attributed to
      subsequent person to person transmission from index cases to intimate contacts
      especially among the same household.

PMID- 17219870
TI  - Satisfaction of clients attending out-patient clinics at Ain Shams University
      Hospitals.
AB  - The current study was conducted to assess client quality at Ain Shams University
      Hospitals Out-Patient clinics. The clients included were 484 subjects selected
      systematically and represented different clinics. Included clients were subjected
      to an interviewing questionnaire after completing contact with the service. The
      study showed that, 7% faced difficulties in getting tickets, 46.7% waited for
      long time. Also, 86.8% stated that the seats were adequate in number, 82.0% were
      satisfied with ventilation, 68.2% reported that W.C. and lavatories were clean
      and convenient, and that examination couches were satisfactory by 57.6%. The
      doctors were patient and listened to clients' complaint in 99%, and 98.6% of
      clients stated that doctors were kind and friendly. Physical safety was
      considered in 96.7% of cases and confidentiality in 68.4%. It was found that
      98.2% of clients trust doctors. Investigations were required for 23.6% of
      clients, and 45.8% reported that the prescribed drugs were not available in the
      Out-Patient pharmacy. The overall satisfaction of the clients was 95.9%. It was
      recommended to shorten the contact time, improve physical environment and promote
      lab. facilities and drug supplies.

PMID- 17219871
TI  - Quality assessment of the primary health care services provided for ARI control
      in Alexandria.
AB  - The aim of the present study was to assess the quality of services provided for
      acute respiratory infections (ARI) control in Alexandria after about five years
      of its integration into primary health care (PHC). The ARI training coverage of
      actively practicing physicians was only 35% and of nurses 37.5%, due to
      inappropriate allocation of trained human resources. The knowledge of trained PHC
      physicians was slightly better than that of untrained staff and both were
      unsatisfactory. The main deficiency was in detecting the dangerous signs and in
      classifying "cough or difficult breathing", which resulted in missing all cases
      of "severe pneumonia" and "very severe disease" needing referral to higher
      levels, in order to reduce the ARI specific mortality rates. The rate of oral
      antibiotic abuse reached about 55%, which was much higher than that found in the
      ARI annual report 1997 and is more likely to be the true figure. On the other
      hand, long acting penicillin was underutilized, due to fear of its allergic
      reaction and oral antibiotics were used instead of it. Therefore, the later were
      unavailable at the PHC facilities for about 7 months, mainly during winter and
      spring time.

PMID- 17219872
TI  - Predictive model of coronary heart disease in Egypt (a disease with multiple risk
      factors).
AB  - As a multifactorial disease and with the need of primordial prevention coronary
      heart disease (CHT), a risk scoring system for the prediction of CHD was devised
      at Community Medicine Department Ain Shams University, Cairo, EGYPT. In this
      matched case-control study of 119 cases and 121 age and sex matched controls,
      current cigarette smoking, lack of siesta, hypertension, diabetes mellitus, low
      occupational physical activity, hypercholesterolemia, marital status, urban
      residence, level of education, work index, coffee consumption, positive family
      history, BMI, elevated W/H ratio, low HDL and elevated TC/HDL were studied for
      association with CHD. The additive risk scoring system based on the results of
      conditional multiple logistic regression identified the first six factors with
      statistical weights of 1, 5, 10, 6, 6, 11, respectively. On back validation
      receiver operating characteristic (ROC) curve, a total score of 17 was found to
      be the cut off point above which there was increased risk of CHD. The overall
      predictive accuracy of this system--equivalent to the area under the ROC curve-
      was 0.873. Future studies need to assess the risk scoring system in population
      based studies.

PMID- 17219873
TI  - Hepatitis C virus transmission in family members of Egyptian patients with HCV
      related chronic liver disease.
AB  - Hepatitis C virus (HCV) infection in Egypt has become a major public health
      problem. In the present study, sexual and intrafamilial transmission of HCV
      infection were assessed in the family members of 200 Egyptian patients (index
      patients) with HCV-RNA positive and biopsy ascertained chronic hepatitis C. Index
      patients were 139 men (mean age 55+/-11 years) and 61 women (mean age 48+/-8
      years). Family members consisted of 200 spouses; 139 women (mean age 45+/-12
      years) and 61 men (mean age 58+/-9 years); and 355 children (183 males and 172
      females, mean age 11.8+/-10 years). All the family members were tested for the
      presence of antibodies to HCV in their sera. Thereafter, HCV-RNA detection by PCR
      and HCV serotype determination were performed in antibody positive contacts.
      Hepatitis C virus antibodies were detected in 28 (14%) spouses, all of them were
      also positive for HCV-RNA. Hepatitis C virus serotypes were identical in HCV
      seropositive patient-spouse pairs (Serotype 4). None of the 355 children involved
      in this study showed HCV antibodies in their sera. No significant difference was
      found between the prevalence of male-to-female and female-to-male transmission of
      HCV. A highly significant association was found between both the age of the
      spouse and the duration of marriage to index patient and HCV seropositivity in
      spouses. Moreover, HCV seropositivity in spouses was significantly related to
      increased serum ALT and HCV-RNA levels, histological severity of chronic
      hepatitis C and to a history of dental care, as a risk factor for HCV
      acquisition, in index patients. It was concluded that spouses of patients with
      HCV viremia and chronic liver disease have an increased risk for acquiring HCV,
      while intrafamilial acquisition of HCV in non sexual contacts seems to be rare.
      The authors suggest that spouses of HCV viraemic patients should be followed
      routinely for markers of HCV infection and liver disease.

PMID- 17219874
TI  - Adult depression in Alexandria, Egypt, 1998.
AB  - The objectives of this population based study were to quantify the prevalence of
      depression among adults in Alexandria, to identify some of its determinants as
      well as to reveal gender differences in its presentation. 300 adults were
      surveyed in their households (10 from each of 30 clusters of the governorate).
      The self administered Beck's inventory for usage in primary care settings was
      used for identifying the depression state. The prevalence rate was 11% with a non
      significant higher proportion among males. Mean age of depressed subjects was
      higher than the free Age interval with highest percentage of cases was 50-60
      years Epidemiologic variables that were found to be significantly associated with
      a higher rate of the condition were being divorced or widowed, a positive recent
      history of stressful life events and having a positive personal history of
      psychological troubles. On the other hand, examined factors like financial state,
      working status and whether the person is a bread earner or dependent in the
      family had no association with the state of depression. Male cases were younger
      than female ones, they also had a higher mean score on the depression scale. The
      genders differed significantly in scores of psychopathological parameters related
      to hopelessness, low self esteem, loss of sexual interest, loss of pleasure,
      guilt, self reproach and suicidal ideation. The authors recommend active case
      finding for depression at the primary care level, instituting counseling services
      for marriage and family relations, intensifying mass media health education
      directed to mechanisms of coping with life stresses and restudying the gender
      differences in epidemiology of depression in a large scale community research.

PMID- 17219875
TI  - Raw wastewater agricultural re-use and risk of protozoal infection in Beni
      Mellal, Morocco.
AB  - This study was carried out to determine the potential risk of protozoal infection
      associated with raw wastewater use for agricultural purposes, among children of
      Beni-Mellal, Morocco. In a randomly-selected sample of 1343 children 740 from 5
      regions which use raw wastewater for agriculture (exposed), while 603 were from 4
      control regions that do not practice wastewater irrigation (unexposed). A
      questionnaire-interview with children and parents was used to collect data on
      demographic, hygienic, and risky water contact risk factors One or more protozoal
      infection was identified among 276(37.2%) of children living in the wastewater re
      use regions, versus only among 22 (3.6%) living in control regions. The overall
      prevalence of 40.1% was observed among boys, and 33.3% among girls residing in
      exposed areas. The two identified protozoa were Entaemoeba histolytica and
      Giardia intestinalis, which infected 34.3% and 5.1% in the exposed population
      compared to only 3.3% and 0.3% in the control population, respectively. We also
      noted that the G. intestinalis prevalence was more than 40% among the children
      under 9 years, but less than 17% for those who were more than 12 years. Also, a
      significant excess of protozoal infection was observed among children who had
      risky contact with agricultural lands (p<0.001). In conclusion, raw wastewater
      use in Beni-Mellal can lead to a high risk of protozoal infections. Adequate
      treatment of wastewater prior to re-use, as well as public health education are
      highly recommended.

PMID- 17219876
TI  - Categorical analysis of factors affecting needs and demands for removable
      dentures among Alexandria Dental Research Center clientele.
AB  - An accurate assessment of dental needs is important to public health planners.
      With this information, it is possible to assess future treatment needs and
      demands for services including those for removable dentures. The present work
      aimed to estimate the magnitude and types of needs, and demands for partial or
      complete removable dentures, to study some factors that may affect the identified
      needs and demands for removable dentures, in addition to studying the factors
      that may affect satisfaction with the dentures. The present study was conducted
      in "Alexandria Dental Research Center". Data were collected by means of interview
      questionnaire, followed by dental examination of all patients attending the
      center for the sake of removable dental restorations for a period of 6 months. A
      further follow up over a period of three months was undertaken to the 330 cases
      recorded. About one third of the cases demanded partial and/or complete dentures
      and were above 60 years old. The first purpose for construction of new dentures
      was mastication, followed by cosmetics. Only one quarter of cases decided to have
      delayed immediate dentures. Diabetics and those having chronic diseases showed
      more demand for complete dentures. The most discriminating variable between the
      demand for different dentures was the missing in the lower anterior teeth
      followed by missing in the upper both anterior and posterior and then missing in
      the upper anterior teeth. Satisfaction score increased with advance of age, among
      males, among those for complete dentures, and those who had had previous
      dentures. Stepwise logistic regression revealed that the best predictor for
      overall satisfaction was the history of having previous dentures. Results of the
      present study, suggest that early screening and treatment of diabetic patients,
      gathering detailed information by means of a questionnaire before new dentures
      fabrication may be an important tool for the dentist in predicting and
      consequently enhancing patient satisfaction with the dentures. Health education
      should stress on the value of restoring missing teeth and all available options
      around this.

PMID- 17219877
TI  - Measurement of KAP concerning hepatitis B among secondary school students in
      Alexandria.
AB  - Hepatitis B infection is a serious health problem throughout the world. Success
      in the prevention of this disease with its fatal consequences depends to a large
      extent on the adolescents' level of knowledge and their awareness about it. As
      well as their attitude and different risk behavior they might practice at this
      age. The aim of the present study was to assess the secondary school students'
      level of knowledge about hepatitis B and to record their perceptions, attitudes
      and practices towards it. Also to identify their health locus of control towards
      the disease. The studied sample included 643 students of both sexes representing
      different senior levels in one educational sector in Alexandria. The used
      technique was self-administered questionnaire. Results revealed that (55.2%) of
      the studied sample had fair level of knowledge about hepatitis B Girls had more
      negative attitude towards the disease than boys. About one half of the students
      (50.4%) were not vaccinated against the disease. Also, the majority of students
      had internal health locus of control regarding hepatitis B. It is recommended to
      integrate knowledge about hepatitis B within formal and informal school programs.
      Community campaigns for vaccinating the adolescents against the disease should be
      carried out.

PMID- 17219878
TI  - Cognitive predictors of self-management behavior of asthmatic children and their
      families in Alexandria.
AB  - The aim of this work was to study self-management behavior (SMB) of asthmatic
      children and their parents, its cognitive predictors as well as its effect on the
      child stress and health care utilization. Data was collected by interviewing 500
      asthmatic children aged 9-18 years and 500 of their parents. The study revealed
      that very low percentage of the respondents had good asthma management behavior.
      The most frequent behaviors were taking medication, going to doctor and avoiding
      asthma triggers. The least practiced behaviors were breathing exercises and
      bronchial hygiene practices. The main predictor for children's SMB which
      constituted 36.3% of its variance was parental management behavior. Most of the
      studied cognitive factors were proved as predictors for children's SMB including
      knowledge, self-efficacy, health locus of control, perceived seriousness and
      barriers. Socioeconomic status was the main predictor of parental SMB, together
      with knowledge, powerful others health locus of control, health value, perceived
      barriers and father's education shared by 46.4% in explanation of its variance.
      Child knowledge, parental SMB, and socioeconomic status were significantly
      predicting health care utilization and level of child stress. A need was
      highlighted for initiation an asthma management educational program to families
      of asthmatic children.

PMID- 17219879
TI  - Materno-foetal transmission of hepatitis B infection.
AB  - A cross-sectional study was carried out on 352 pregnant women, chosen randomly
      from those admitted to the labour ward of Ain Shams University Hospitals,
      Abbassia, Cairo, Egypt. This study was conducted to determine the prevalence of
      HBsAg among pregnant women and estimate the materno-foetal transmission. The
      prevalence of HBsAg among studied women was 15.3%, however, 7.1% showed
      inconclusive positive results. The materno-foetal transmission was documented in
      51.8% of positive HBSAg women. Hepatitis B infection among studied women was
      usually acquired after 20 years of age. Logistic regression model with stepwise
      forward selection, demonstrated that maternal age, past history of blood
      transfusion and abortions were contributing factors for +ve HBsAg maternal
      status, while parity and past history of abortions were contributing factors in
      materno-foetal transmission.

PMID- 17219880
TI  - Gastric mucosal Helicobacter pylori distribution and its implications.
AB  - In tile present study the clinicopathological aspects of H. pylori infection in
      different parts of the stomach were investigated in 36 patients. The results
      showed that 28 patients (77.8%) were H. pylori positive and 8 patients (22.2%)
      were H. pylori negative by histopathology and confirmation with modified Giemsa
      stain. There was no statistically significant difference belween H. pylori
      positive and negative patients regarding dyspeptic symptoms or intestinal
      metaplasia histopathologically. Histopathological examination revealed chronic
      gastritis with mononuclear cell infiltration in all studied patients. According
      to the degree of cell infiltration, chronic gastritis was graded as mild,
      moderate and severe. There was a statistically significant difference between H.
      pylori positive and H. pylori negative patients regarding both severity and
      activity of chronic gastritis in the antrum and body compared to the fundus.
      Also, there was significant correlation between the grade of H. pylori
      colonization and the grade of chronic active gastritis on one hand and between H.
      pylori infection and atrophic gastritis. The serum anti-H. Pylori - IgG positive
      cases who were H pylori negative by history, showed atrophic gastritis acid
      intestinal metaplasia. This may be due to the fact that the mucosa has become
      inhospitable for H. pylori.

PMID- 17219881
TI  - Hypertension control indicators among rural population in Egypt.
AB  - This study was designed to be a house to house survey to fulfill an interview
      questionnaire and measure blood pressure for 1927 rural inhabitant at "Bany
      Magdoul" village located at Imbaba district of Giza governorate. The response
      rate was 96.4%. The prevalence of hypertension among study sample was 27.9%; only
      15.5% were aware of being hypertensives. Among the hypertensive patients only
      25.9% were receiving regular treatment. Also, the proportion of controlled
      hypertension among known hypertensives was 24.2%. It was concluded that
      hypertension is an emerging problem in rural areas and the control indicators are
      low in comparison to other surveys.

PMID- 17219883
TI  - Nutritional status of institutionalized and free-living elderly in Alexandria.
AB  - Because of an increase in the number of elderly and the problems of nutrition
      associated with them, it is of interest to study the nutritional status of
      elderly persons in Alexandria City. The purpose of this study was to assess the
      nutritional status of elderly population and to compare between the nutritional
      status of those institutionalized and those living free. The study was conducted
      on 240 elderly persons (120 institutionalized and 120 free living) selected
      randomly from institutions and from different sites. The basic data, weight,
      height, body mass index (BMI) of each were recorded. Dietary intake study was
      done by using 24 hours recall for 3 consecutive days and food frequency were used
      to obtain the best estimate of food intake. Energy and nutrient intakes were
      obtained and compared with the recommended dietary allowance (RDAs). The main
      findings of the study revealed that the mean age of the institutionalized elderly
      was greater than those living free. Percent of obesity among females was 71.7%
      among free living and 45% among institutionalized. Under-nutrition was present in
      11.7% and 8.3% of institutionalized males and females respectively. Food habits
      showed that institutionalized subjects consume more amounts of many food items
      than free-living. Total daily energy intake was found to be below the
      recommendation for all subjects, with higher intake among institutionalized than
      free living. Nutrient intakes among institutionalized and free living elderly
      were inadequate except thiamin, riboflavin, vitamin C and iron. The nutrients
      least adequately supplied in the diets of elderly are vitamin A and calcium along
      with energy deficits. In conclusion both institutionalized and free living are at
      risk for developing nutrient deficiencies. Deficient energy, calcium and vitamin
      A are common problems among most subjects. The composition of the diet among free
      living subjects seem to be also poor in some micronutrients. We recommended a
      nutrition intervention program and nutrition education to improve nutritional
      status of elderly people.

PMID- 17219882
TI  - Community perceptions of dietary and environmental factors as cardiovascular
      diseases risk determinants.
AB  - This work was carried out to assess the community's perception of the relative
      importance of various dietary, environmental and lifestyle factors as CVDs risk
      determinants and to investigate the beliefs of the community on issues related to
      CVDs. A household cluster sample survey was conducted in Alexandria city. The
      total sample was 600 persons aged > or = 18 years Results of this work revealed
      that public awareness of the magnitude of CVDs in the community was high. There
      appeared from the large percentages of incorrect or unsure responses that the
      community tended not to perceive the importance of different lifestyle habits
      specific to CVDs. 'Sociodemographic variables that were significantly associated
      with good perception were higher educational and occupational levels of the
      subjects. It was also revealed, that although the community has confidence in
      advice on preventive behaviours, it was reluctant to ask about screening tests.
      Moreover, the community is receiving some information about issues related to
      CVDs and, a desire for more health information from doctors and health agencies
      was evident. In spite of the majority of the subjects were willing to follow
      advice aimed to reduce their risk of getting CVDs, they were not sure what that
      advice might be. Studies of this type clearly have the ability to provide a range
      of information which ought to be available to those responsible for the planning
      of health promotion and education initiatives.

PMID- 17219884
TI  - Respiratory enzymatic changes among workers in glue industries.
AB  - The aim of this study was to investigate the respiratory enzymatic changes among
      workers in glue industries. Blood and urine samples were collected from 30
      exposed workers and 30 age and sex matched control subject from the
      administrative department of the same factory. Different respiratory enzymes were
      analyzed in blood. The level of urinary phenol was also determined. The median
      level of different respiratory enzymes (catalase, glutathione peroxidase,
      glutathione reductase and carbonic unhydrase) were significantly higher in the
      exposed workers compared to control subjects. Also the median level of urinary
      phenol was significantly higher in exposed workers compared with that of
      controls. Attention should be paid to the different occupational health hazard,
      existing in different types of glue industries.

PMID- 17219885
TI  - Health and lifestyle survey: community's attitudes to health and barriers toward
      lifestyle change.
AB  - The study was carried out in Alexandria City. A household cluster sample survey
      was conducted. The total sample was 300 subjects. The objectives of this work
      were to assess the community's attitude of specific health issues, examine the
      relationship between subjects' determined level of risk and their beliefs about
      and desire to modify smoking, current diet and level of exercise as well as to
      portray the possible barriers to adopting healthier lifestyle. The survey results
      revealed that generally the community reflects positive attitude to health that
      was significantly associated with younger age, higher educational and
      occupational levels and absence of risk factors. The significant predictors of
      subjects' perception of the health risk of current diet were smoking, obesity,
      high dietary fat intake and physical inactivity. All the studied risk factors
      were found to be significant predictors of the subjects' attempt to change their
      current diet. In investigating the main barriers to diet change, subjects' lack
      of knowledge on how to make their diet healthy topped the list, while lack of
      will power topped the list of barriers against quitting smoking. Pressure of time
      was stated first as a barrier against changing subjects' exercise level. Further
      researches of this type are required to yield detailed information for the whole
      nation to guide for health and lifestyle intervention strategies.

PMID- 17219886
TI  - Falls among institutionalized elderly in Alexandria.
AB  - Falls are a common geriatric problem causing considerable morbidity, mortality,
      and affecting the quality of life of many elderly people. A cross sectional study
      was conducted to determine the prevalence and risk factors of falls among elderly
      people living in geriatric institutions in Alexandria. The total sample included
      103 elderly females and 62 elderly males from six institutions. All participants
      were subjected to interviewing questionnaire to collect data about history,
      circumstances, outcome of falls, previous falls and history of diseases and drug
      intake It included also data about activities of daily living. Anthropometric
      measurements, blood pressure, postural hypotension assessment, complete physical
      examination and Tinetti scale for balance and gait could be completed for a sub
      sample. The prevalence of falls was 32.1%. Most of the falls occurred during the
      daytime (77.4%), mainly in the bedroom or in the way from bed to bathroom (37.7%
      each). The most likely causes were slip/trip (41.5%) followed by
      dizziness/vertigo (32.1%). Fractures occurred in 20.8% of falls. Advanced age (70
      79, 80 years and above), history of three or more falls, history of disability
      from previous falls, history of visual problem, history of cardiac and
      antihypertensive drug use, and mild impairment of balance and gait were
      significant risk factors for falls in the univariate analysis. All these factors
      except for the impairment of balance and gait were also significant predictors of
      falls in the multivariate analysis.

PMID- 17219887
TI  - Screening for hepatitis A virus antibodies among a disadvantaged group of
      preschool children in Alexandria.
AB  - Hepatitis A virus (HAV) immunity in a group of socially and economically
      deficient preschool children in Alexandria has been investigated. A total of 228
      randomly selected children were enrolled. Saliva was collected from every child
      using a cotton wool swab. Anti-HAV was investigated in the collected saliva by a
      competitive ELISA technique utilizing a commercially available kit. The results
      revealed that among the investigated children 60 (26.3%) were anti-HAV positive.
      The mean age of anti-HAV positive children was 4.43 years +/- 0.21 years. Ten
      (33.3%) couples were siblings, 2 (3.3%) children gave a positive history of
      jaundice. As regards housing conditions; 34 (56.7%) of anti-HAV positive children
      had indoor sources of water supply and 26 (43.3%) had outdoor ones. The mean
      crowding index was 3.35 +/- 1.72. Positive anti-HAV was significantly more
      prevalent among older (P < 0.05) and among female children (P < 0.02). In
      conclusion, the routine administration of hepatitis A vaccine, combined with
      improvements in sanitation should reduce the incidence of acute illness and
      complications associated with the disease thereby decreasing the spread of HAV in
      developing countries.

PMID- 17219888
TI  - Smoking-related behaviour and attitudes among medical students in Alexandria.
AB  - As a preliminary step toward incorporating a tobacco education and intervention
      program into our undergraduate medical curriculum, this study was designed to
      assess students' smoking-related behaviour, knowledge and attitudes towards
      tobacco, and perceptions of their future role as doctors in smoking intervention.
      A cross-sectional, study was conducted in the university year 2001/2002 on a
      representative sample of male medical students enrolled in 4th and 5th years at
      Alexandria University. A total of 320 students across the 2 years completed the
      survey. The smoking rate among medical students was 17.5% (10.9% smoked daily and
      6.6% occasionally). The awareness of harmful effects of smoking and knowledge
      about the causal role of tobacco in the development of specific diseases were
      deficient. The intention to perform smoking intervention in the future as doctors
      seemed unsatisfactory. About 85% of the students thought that doctors should
      carry out smoking cessation advice depending on the disease, while the rate of
      those who thought so irrespective of the disease did not reach 44%. Current
      smokers thought less actively about smoking intervention than non-smokers. Nearly
      two-thirds of students (65.3%) felt they were not sufficiently prepared for
      caring or counseling smokers, and only 31.9% of students were convinced of the
      effectiveness of the doctor's advice to stop smoking. Seventy-seven and half
      percent of them desired specific training in smoking intervention. Non-smokers
      were more in favour of legislative actions to discourage tobacco use than current
      smokers. These findings suggest that medical school authorities should design and
      implement an appropriate basic training aimed at better preparing medical
      students for their future role in prevention of smoking. Specific teaching of
      medical students about smoking-related diseases and a patient-centered smoking
      cessation intervention is required to provide future medical practitioners with
      the knowledge and skills they need to effectively intervene with smokers.

PMID- 17219889
TI  - Impact of life style on the nutritional status of medical students at Ain Shams
      University.
AB  - This cross sectional study was carried out to assess the nutritional status of
      medical students and to determine its relation to their life style. The study
      involved 317 students at, Am Shams University. Anthropometric measurements such
      as weight, height, mid-arm circumference, triceps skin fold thickness and body
      mass index were measured. The students completed a self-administered
      questionnaire including data about some life style factors and food-frequency
      consumption. The study revealed that 41.3% of the students were of normal weight
      while 9.5% of the sample were underweight, 36.9% were overweight and 12.5% were
      obese. The mean mid upper arm circumference (MUAC) and mid arm muscle
      circumference (MAMC) of males was significant higher than that of females, while
      the mean triceps skin fold (TSF) of females was significant higher than that of
      males. The food frequency questionnaire analysis showed that most of students
      consume all food groups items faire. There was no statistical significant
      difference between the body mass index (BMI) of students and different types of
      food consumption. About two thirds of the students used to practice exercise,
      26.9% of the students practiced exercise for less than 2 hours per week, while
      33.9% of them for more than 2 hours. There was no statistical significant
      difference between the BMI of students and different types of exercise. However,
      there was significant higher percentage of males play sports and practice running
      (44.7% and 19.4% respectively) compared to (11.7% and 8.1%) of females. Sixty
      four percent of the students usually have regular meals. About 87.2% of obese
      compared to 64.9% of normal weight students eat snacks between meals, the
      difference was statistically significant. Obese individuals eat more during
      watching television and during feeling of stress compared to non-obese and the
      difference was statistically significant. The duration of practicing exercise,
      sports and playing computer was significantly higher in males than females.
      However, the duration of watching television was significantly higher in females
      than males. Logistic regression analysis results showed that family history of
      obesity and some life style factors as duration of computer use, eating more
      during stress time and snacking between meals were important risk factors for
      obesity. We concluded that about half of medical students were overweight and
      obese. The most important life style factors responsible for obesity were longer
      time spent using computer, eating more during time of stress and snacking between
      meals. Also, genetic factors played an important role in development of obesity.
      It is recommended to develop nutritional education and physical activities
      programs to face the problem of increasing the rate of overweight and obesity
      among university students.

PMID- 17219890
TI  - Mental health knowledge and skills among preschool nurseries' staff in Alexandria
      and the effect of an in-service training programme.
AB  - Day care centres and kindergartens, have potential effects on children's
      physical, social and mental developments. The present study was carried out to
      assess the knowledge and skills of nurseries' staff in Alexandria as regard child
      mental health, and to evaluate the outcome of an in-service child mental health
      training programme. For this purpose 10% of the registered nurseries in
      Alexandria were selected by the stratified random sampling technique using
      proportional allocation (n = 54) to represent the six districts of Alexandria.
      Data were collected from all staff members of selected nurseries present during
      the visits to the nurseries (n = 172). A self-administered questionnaire was used
      and including general information about the respondents, and their knowledge and
      skills regarding child mental health. From the total sample, 52 were randomly
      selected to attend a 2-day in-service mental health training programme. Results
      of the study revealed deficiency of knowledge and skills of the staff in most of
      the tested items. However, staff who were graduates of Faculties of Kindergarten,
      Education and Arts were significantly better than other educational categories
      regarding the number of correct or partially correct answers. The training
      programme proved to cause a significant improvement in knowledge and skills of
      the staff in most of the items. It was recommended to increase the staff who have
      educational background of kindergarten and education, to give more attention to
      continuous evaluation of nurseries' staff knowledge and skills, and to apply a
      maintained system of pre and in-service child mental health training programmes
      for them.

PMID- 17219891
TI  - Accident prevention program in a glass factory in Shoubra El Khema district.
AB  - BACKGROUND: An accident can be defined as an unplanned event that results in or
      suggests the possibility of personal injury, property damage production
      interruption diminished health or environmental damage. The accidents have a cost
      impact on the employees and the company itself. OBJECTIVE: This intervention
      study was carried out to decrease the accident rate in a glass factory in Shoubra
      El-Khema district. METHODS: A glass factory in Shoubra El-Khema was selected to
      implement an intervention program. The program was done through three phases. 1.
      A preliminary interview questionnaire. 2. Seminars of health education were done
      to all workers and managers with availability of health education posters,
      establishment of accident committee and a new reporting system, contract with a
      housekeeping company was done and also training of some leaders. 3. Concurrent
      and final evaluation of the program was done. RESULTS: The incidence rate,
      frequency and severity rate of accidents were decreased at the end of the year
      after the intervention program. The differences were statistically significant.
      The opinions of the workers and managers about the different causes of accidents
      were changed. The belief of the workers and managers about efficiency of health
      educatio program was changed. Some leaders were trained on skills of health
      education. Modification of reporting and notification system was done.
      CONCLUSION: This intervention study succeeded in decreasing accidents rates and
      increasing the awareness of the managers to decrease accident rates. The beliefs
      and thoughts o both workers and managers became near to each other. The
      production loss due to days lost by accidents was reduced. RECOMMENDATIONS:
      Upgrading process in the factory are recommended to eliminate the hazards at
      source. Sustaining and continuation of the established preventive program should
      be done. Trying to apply the program in similar factories is also recommended.

PMID- 17219892
TI  - Partial sequence at 2BC region of HAV isolated from stool of acute sporadic HAV
      patients.
AB  - More than 20 hepatitis A virus (HAV) strains that can be distinguished from each
      other are known till now. In the present study, a cytopathic strain of HAV (HA
      10) was isolated in Egypt from stool of acute sporadic cases. The isolated strain
      showed CPE in early stages of adaptation in cell culture. Accordingly, the first
      step in the work was to confirm the presence of HAV, the second step was to prove
      that no enteric virus is associated with the isolate and finally to try to know
      the reason for that rapid adaptation in cell culture. So, RT-PCR was carried out
      for different regions of the viral RNA (5'ntr, VP1, VP1/2A, 2B and 2B/2C) also,
      enterovirus primers (5'ntr) were used. Reference HAV strains such as HM-175, HAS
      15, MBB and 18F were used for comparison. Segment of 2BC region of the viral RNA
      was sequenced and compared with the nucleotide sequence of the reference HAV
      strains at the same region. The results revealed that HA-10 isolate react with
      all HAV primers and similar in this behavior with 18F and HM-175 strains. The
      nucleotide sequencing showed that there are 16 mutations in HA-10, two of them in
      2B and the others in 2C region which may explain the reason for the highly
      adaptation of HA-10 isolate than 18F. As a result of this study, HA-10 may give
      us a highlight on HAV replication and also, the isolated strain may be useful for
      vaccine development.

PMID- 17219893
TI  - Occupational risks for preschool teachers in Alexandria.
AB  - We studied the occupational hazards facing the preschool teachers in Alexandria.
      The study included 106 preschool teachers working in kindergarten in Alexandria.
      They were all in the childbearing age. Their ages ranged from 20-30 years. The
      occupational health risks were studied by questionnaire including data about
      communicable diseases, occupational stress and ergonomic hazards leading to
      musculoskeletal problems. There was a significant increase of respiratory illness
      in unhealthy places (X2 = 24.22, p < 0.05), a significant increase of bone ache
      among preschool teachers in the presence of several jobs (X2 = 27.09, p < 0.05).
      The study also revealed a significant increase of bone ache in teachers having
      psychological stress (X2 = 35.34, p < 0.05) and teachers having job stress (X2 =
      28.36, p < 0.05). There was a significant association between type of education
      and both headache (X2 = 20.48, p < 0.05) and psychological stress (X2 = 11.90, p
      < 0.05). Proper management of the environment will decrease occupational risks
      for preschool teachers.

PMID- 17219894
TI  - The potential role of rattus rattus in enzootic cycle of Rift Valley Fever in
      Egypt 2-application of reverse transcriptase polymerase chain reaction (RT-PCR)
      in blood samples of Rattus rattus.
AB  - A reverse transcriptase -polymerase chain reaction (RT-PCR) was applied to detect
      Rift Valley Fever Virus (RVF-V) in blood samples of Rattus rattus (R. rattus)
      collected from 3 different governorates of Egypt, Alexandria, Behira and Minia
      governorates (one hundred each). Out of 300 blood samples 29(9.67%) were positive
      for RVF-Virus by RT-PCR with higher percent in Behira governorate rural areas
      (16%), followed by Minia governorate rural areas (13.85%) while the lowest
      percent was in Alexandria governorate urban areas (0.00%). The overall percent in
      rural areas were (13.5%) while it was only (2.0%) in urban areas. Our Study
      suggests that, this R. rattus play an important role in the maintenance cycle of
      RVF-V in rural areas of Egypt.

PMID- 17219895
TI  - Mortality stastistics as indicators of quality of hospital care.
AB  - Death rates have always been important information for hospitals to provide a
      solid base for the evaluation of the quality of their medical care. This study
      was carried out to find out the gross death rate (GDR) as well as net death rate
      (NDR) in King Fahad hospital, Jeddah, Kingdom of Saudi Arabia (KSA) in the period
      from 1994-2000 and also to find out demographic characteristics of deaths in the
      year 2000 according to ICD-10 as indicators of quality of hospital care. Medical
      records of discharged patients including deaths during the year 2000 were
      reviewed (13386). Complete data about deaths were obtained. Results of the
      studied hospital showed gradual decrease in GDR from 5.8% to 4.5% (1994-1998)
      then slight increase from 4.9% to 5.0% (1999-2000) but still below the year 1994
      (5.8%) and also there is gradual decrease in NDR from 4.6% to 3.6% in the studied
      period. GDR in different departments of the hospital during the year 2000 showed
      that Medical ICU was the highest (24.5%) followed by Surgical ICU (17.9%)
      followed by Cardiac ICU (14.3%) while GDR in the Medical department was found to
      be (12.9 %) of the discharged subjects. According to nationality; proportional
      mortality rate (PMR) of Saudis represented 62% of total deaths followed by
      Yemenis (8.2%) meanwhile Egyptians represented 3.7% of total deaths in the
      studied year. As concerned to age groups; the highest PMR was found among those
      aged 65-74 years (21.9%) while the lowest PMR was found among those aged 13-24
      years (4.2%). The highest PMR of deaths during the studied year was reported in
      March (10.4%) followed by April (9.7%) then February (9.4%) which are the months
      of pilgrimage season while the lowest frequency was found in December (6.9%).
      Also PMR was found to be higher among females (57%) compared to males (43%).
      According to International Classification of Diseases (ICD-10); diseases of the
      circulatory system were found to be the commonest underlying cause of death in
      the studied year. It represented 35.5% of all deaths followed by neoplasms
      (11.2%) while the lowest cause reported was mental and behavioral disorders
      (0.1%). In conclusion, combination of the previous indicators and comparing the
      results with other hospitals in different countries indicates good quality of
      medical care in the studied hospital.

PMID- 17219896
TI  - Risk factors of febrile seizures among preschool children in Alexandria.
AB  - The study design was a case control study to identify the risk factors of febrile
      seizures. Total sample of 28 children, their ages ranging from 12 to 60 months,
      with febrile seizure were matched with control group of 60 children of the same
      age group with fever without seizure. The peak age of first febrile seizure was
      between 6 and 12 months. The significant risk factors were upper respiratory
      tract infection (p < 0.05), family history of febrile seizures (p < 0.0001).
      Prematurity (p < 0.005), problems during gestation (p < 0.005), family history of
      epilepsy (p < 0.005) and problem during labour (p < 0.0005).

PMID- 17219897
TI  - HIV/AIDS perceptions and risky behaviors in squatter areas in Cairo, Egypt.
AB  - The aim of this work was to assess HIV/AIDS perceptions and risky behaviors of
      adults living in squatter areas in order to take decisions about the relevant
      messages and health education methods that should be used to prevent HIV
      transmission in the studied communities. Two methods were used to collect data in
      this cross sectional study, focus group discussion and structured interview. The
      study was carried out in six squatter areas in Cairo, four of them located in
      west Cairo and two in east Cairo. RESULTS: 237 community members and community
      leaders shared in the study, 44.7% were males and 55.3% females, 64.1% were
      married and 34% single. Community members represented two-thirds of the sample
      while one-third were community leaders. Participants expressed strong eagerness
      to know more about HIV/AIDS. Poor knowledge and misconception about HIV/AIDS was
      remarkable. The study revealed several misconceptions regarding modes of
      transmission and preventive measures that could be used to protect oneself from
      HIV/AIDS. Heterosexual extramarital relationships and i.v. drug transmission were
      the HIV/AIDS risky behaviors considered to be prevalent in these communities.
      AIDS risky behaviors appear to be more prevalent in the four squatter areas in
      west Cairo than in the two squatter areas located in east Cairo. Adolescents were
      considered at high risk of contracting AIDS because of the risky behaviors they
      practice. Social non-acceptance of females who practice HIV/AIDS risky behaviors
      is much stronger than non-acceptance of males who practice the same risky
      behaviors. TV movies were the main source of information about HIV/AIDS. Parents
      played no role in providing adolescents with information about AIDS. The possible
      role of teachers in HIV/AIDS education is unclear because of the negative
      attitude of people towards teachers.

PMID- 17219898
TI  - Recurrent abdominal pain among a sample of Egyptian children in relation to
      family and school related problems.
AB  - Recurrent Abdominal pain (RAP) is a common feature of growing children especially
      above the age of five. It may be experienced for either organic or non-organic
      (psychogenic) reasons. The main objective of the present study is to investigate
      the possible relation between the occurrence of RAP and some family and school
      related problems. It is a descriptive cross sectional study designed to assess
      children aged 7-12 years, of both sexes, attending El-Salam health insurance
      clinic (Eastern Cairo) for their RAP. Seven hundred children (400 boys and 300
      girls) suffering from RAP were investigated. They were subjected to routine
      investigations (urine and stool analysis, complete blood picture, x-ray abdomen)
      to exclude the possible organic cause for their RAP. A specially designed
      questionnaire for the purpose of the present study was applied after testing its
      validity (it was judged by 10 professors of Psychology, Psychiatry and community
      medicine before its use). It was applied individually on each child (or his/her
      caregiver). Data were collected from each subject as regard: His/her personal
      history, socio-demographic characteristics, characters of RAP (its type,
      severity, onset, duration, frequency, site and its relation to other symptoms),
      some organic and psychological symptoms and history of family troubles and school
      related problems. Data were collected, tabulated and analyzed using Chi- square
      test to compare children of organic and non-organic RAP. Results revealed that
      RAP was mostly non-organic in origin (65.7%). It was commonly associated with
      family troubles (59.7%) and school related problems (40.3%). Children with non
      organic RAP expressed many psychological symptoms especially; tantrums (41.1%),
      phobias related to school (17.4%) as well as continuous crying (13%) and appetite
      loss (14%). There was significant female predominance (p = 0.0000) in expressing
      RAP in direct relation to family troubles and school related problems compared to
      boys. Non-organic RAP was described as mild (68.2%), gradual (64.3%), poorly
      localized (79.6%) pain, that was experienced more or less on daily basis (79%),
      and lasts for shorter duration (68.5%) [less than 15 minutes]. It was commonly
      associated with headaches (46.9%), diarrhea (36.9%), and other pains all over the
      body (13.4%). It was related neither to meals or to sleep (71.1%). On the other
      hand, RAP (both organic and non-organic) was not significantly related to child's
      socio-demographic background. Results were discussed and interpreted with results
      of other researchers. Many recommendations were introduced for proper assessment
      and management of such children.

PMID- 17219899
TI  - Distortion of the used plastic syringes by hot air ovens.

PMID- 17219900
TI  - The inhibitory effect of garlic (Allium sativum) on growth of some
      microorganisms.
AB  - The aim of the present study was to compare between the anti-microbial activity
      of fresh garlic bulbs and that of its water extract against the potent food
      pathogens Staphylococcus aureus, Esherichia coil, Salmonella typhi and Bacillus
      cereus. Garlic segments with different concentrations (1%, 5%, and 10%) were
      used. Another 100 gms of garlic segments were weighed and mixed with 100 ml
      distilled water to prepare water extract of garlic, then 1000, 500 and 100
      microg/ml were prepared. These concentrations of garlic were mixed with prepared
      cultures of E. coli, Staph. aureus, Bacillus cereus, and Salmonella typhi. The
      inhibitory effect of garlic was determined using Spectrophotometer for garlic
      segments and by comparing with control plates for the water extract of garlic.
      Results showed that the higher the garlic concentration, the higher was the
      microbial reduction percent. Water extract of garlic exhibited a higher microbial
      reduction percentage than fresh garlic.

PMID- 17219901
TI  - The effect of bread making steps on the degradation of aflatoxins produced as a
      result of single inoculation with Aspergillus flavus and combined inoculation
      with Aspergillus flavus and Aspergillus ochraceus.
AB  - This study aimed to determine the effect of bread making steps on the stability
      of aflatoxin. Sakha 8 wheat and Gemaiza 5 wheat cultivars, were used in the
      present study. They were inoculated with a dense spore suspension of toxigenic
      fungal species of Aspergillus flavus and a non toxigenic species of Aspergillus
      ochraceus singly and combined. Aflatoxin concentration was determined in the
      whole wheat grain, after milling, after fermentation, and after bread-baking
      process. Results showed that the highest reduction percentage for the total
      aflatoxins (81, G1 and G2), was in Sakha 8 (32.96%) (single treatment), Gemaiza 5
      (19.54%) (single treatment ), Gemaiza 5 (18.65%) (combined treatment), and
      finally in Sakha 8 (16.49%) (combined treatment). There was no significant
      difference (p < 0.05) in aflatoxins content between Sakha 8 and Gemaiza 5 treated
      singly and in a combined way before and after milling process. In the mean time,
      the percentage of AFB1, AFG1 and AFG2 were reduced by 31.98%, 44.53% and 35.35%,
      respectively, while the total aflatoxins concentration were reduced by 41.17%
      after baking. Results also showed the presence of a significant difference at p <
      0.05 among the whole grain, after milling and after baking concerning AFG1, AFG2
      and the total aflatoxins content. No significant difference was found in case of
      AFB1.

PMID- 17219902
TI  - Occupational stress among paramedical staff working in primary health care
      centers in Abha, Saudi Arabia.
AB  - Occupational stress among paramedical staff in Primary Health care centers was
      not extensively studied as in medical or hospital nursing staff. The aim of the
      present study was to reveal the work characteristics in the PHC centers in Abha
      city, Saudi Arabia, with its stressful hazardous conditions as perceived by the
      working paramedical staff. The study revealed that this staff is facing heavy
      workload with low decision and control latitude. This is the most hazardous
      condition generating stress among working populations. As most of them are
      foreigners the language barrier compounds the problem. It was noticed however
      that most of them enjoy good social support from both colleagues and home members
      that might play a modifying role alleviating stress. This group of workers needs
      special care and continuous evaluation of mental stress induced by their working
      conditions.

PMID- 17219903
TI  - Development of mortality statistics at governmental hospitals, Egypt.
AB  - Mortality statistics are of crucial importance to epidemiological research.
      Sources of mortality data in Egypt are many. The first records are hospital
      records, which submit its data to health office records and lastly civil register
      office records. Hospital records include hospital death notification certificate
      and hospital mortician register. Health office records include mortality
      register, death certificate and death notification report to civil register
      office. The latter is designed to have a coded data and cause of death according
      to ICD-10. It is supposed that the death notification report that originates from
      the hospital is the source of data for the rest of records and registers. So, all
      these data for the same dead person must be the same. Quality of the original
      data will reflect itself on the rest of data. This study aims at establishment
      and assessment of automated system for management of mortality data at (hospital
      1, affiliated to Ministry of Scientific Research) and comparing this system and
      its output with another one (hospital 2, affiliated to the Ministry of Health).
      The tools of this study are review of the above mentioned records and registers
      and personal interviews. Death certificate itself is not reviewed, as it is not
      found in the health office. One-year data sample was chosen for the study.
      Development of the system at hospital 1 is based on system analysis, design,
      implementation, and evaluation. Results showed that automated system of hospital1
      have the values of automation as timely retrieval and decreasing the error of
      transcription. Epi-Info software package gives easy statistical analysis and the
      potential for record linkage. Comparison between hospital death notification
      certificate that originated from the hospital and health office register showed
      97.4% matching for words or expressions in hospital 1 and 50.0% in hospital 2.
      Comparing hospital death notification report with that originated from health
      office to related civil office, showed 100.0% matching for hospital1 and 86.7%
      for hospital 2. As regards correctness of reporting the cause of death, 97.4% of
      deaths in hospital1, and 29.9% in hospital 2 showed non-specific cause of death
      reported as circulatory and respiratory distress, that is the actual cause of
      death is not reported. It is concluded that, unification and automation of the
      systems is a requirement. Record linkage between different locations of mortality
      data is recommended. Training on reporting and coding the cause of death is also
      recommended.

PMID- 17219904
TI  - Pattern of water contact activities in relation to S. mansoni infection in rural
      area in Giza Governorate, Egypt.
AB  - Schistosomiasis is associated with human behavior in relation to water. Study of
      different patterns of water contact activities would help in planning strategies
      for control. This study aims to describe patterns of water contact activities in
      relation to S. mansoni infection in El-Shobak El-Sharki village in Giza
      governorate, in Egypt. A sample of 695 households was taken from about 127
      houses. They provided stools samples and a water contact questionnaire for
      different activities, regions, sites, time of the day, duration of activities,
      patterns in different age and sex groups. Univariate and multivariate analysis of
      data was done. It was found that, adult males had the highest prevalence rate,
      then adult females while children had the least (33.5%, 27.5% and 17.4%
      respectively, p-value < 0.0001). Infection rate is higher in those having water
      contact activities, with Odds Ratio (OR) 2.01 and 95% Confidence Intervals (CI)
      (.94-4.24). Other significant factors are, the site of activities, time of the
      day and duration of contact, with p-value < 0.05. The highest score for the
      different patterns of activities in adult males are mainly occupational as
      agriculture and irrigation, their OR (95% CI) are 2.82 (.91-5.94) and 2.58 (.89
      5.41), respectively. As regards females, the highest score is for domestic daily
      activities as washing infant clothes and utensils, their OR (95% CI) is 2.19 (.91
      4.73) and 1.83 (.80-4.16) respectively. Children have the least score, their
      activities is mainly recreational as swimming, OR (95% CI) is 1.77 (.79-4.02).
      Multiple logistic regression analysis revealed that, male's activities and their
      longer duration are highly significant factors with prevalence as the dependant
      variable, OR (95% CI) is 3.07 (.73-8.19) for activities, and is 3.67 (.31-9.38)
      for duration. It is concluded that, human exposure pattern, in general, favors
      the transmission of S. mansoni. Prevalence of infection coincides with water
      contact activities in different age, sex and farming occupation. So, the control
      of S. mansoni in Egypt is not a pure medical affair. It needs multidisciplinary
      upgrading actions to be taken in different sectors of agriculture and irrigation
      reform in Egypt.

PMID- 17219905
TI  - Impact of health education program about reproductive health on knowledge and
      attitude of female Alexandria University students.
AB  - In Egypt, adolescents don't have enough and/or correct knowledge regarding
      reproductive health. Health education interventions are widely seen as the most
      appropriate strategy for promoting young people's sexual health. The aim of the
      present work was to assess the impact of a short-term health education program
      about reproductive health on knowledge and attitude of female Alexandria
      university students. Quasi-experimental study (pre-post testing control group)
      was carried out among 682 female university students living in the university
      hostels, 354 students represented the intervention group (Ezbet-Saad hostel) who
      received the program and 328 students constituted the control group (El-Shatby
      hostel). The study revealed that no one had satisfactory knowledge level while
      61.7 % and 38.3% respectively had fair and poor levels. The low knowledge level
      was more evident regarding the questions about: the meaning of the term
      'reproductive health' (only 5.1% gave correct complete answer), the benefits of
      premarital examination (only 37.9% reported complete answer), the investigations
      done for the pregnant woman (only 28.3% gave complete answer) the benefits of
      breast feeding (only 8.2% reported complete answer), methods of family planning
      (only 36.4% gave complete answer), side effects of female genital mutilation
      (only 4% reported complete answer), sexually transmitted diseases and methods of
      protection (only 11.9% and 3.9% reported complete answer). It was evident that
      32.6% had an overall positive attitude level, 46.3% were in the neutral level and
      21.1% had a negative level. It was also found that students of highly or
      moderately educated mothers and of high social class reported significantly
      higher knowledge score about premarital examination, age of marriage and breast
      feeding than those of non-educated mothers and of low social class. After the
      intervention program there was a significant improvement in the majority of
      knowledge questions from pre to post test in the intervention group and no
      absolute changes were detected in the control group. The highest percentage of
      gain scores (33.3%) was detected for knowledge about the term 'reproductive
      health' and female genital mutilation. A significant gain score of 25% was
      observed for the knowledge about sexually transmitted diseases. Also there was a
      gain of 20% in the median score concerning the knowledge about breast feeding and
      family planning. A significant shift towards a positive attitude was found among
      the intervention group.

PMID- 17219906
TI  - Risk assessment for obstetric interventions.
AB  - AIM: This study was conducted to reveal the determinants of obstetric
      interventions in El Shatby maternity hospital, the only obstetric care facility
      providing tertiary care in Alexandria METHODS: Parturient admitted to the
      delivery room during the morning and afternoon shifts between April and February
      2002 were enrolled in the study. Data were obtained by interview questionnaire
      complemented by thorough obstetric examination and close monitoring of the labor
      progress. Data were analyzed using the univariate and multivariate regression
      analyses. RESULTS: out of the 3201 parturient who attended the hospital, 1302
      were included in the study. Nearly three-fifths (61.7%) of parturient had a
      vaginal delivery. For the remaining proportion, delivery was accomplished by an
      elective (20.3%) or emergency (17.1%) cesarean section while few (0.9%) had an
      instrumental vaginal delivery. Operative obstetric intervention was determined by
      both maternal and fetal factors. For both primiparae and multiparae, the risk of
      elective cesarean delivery was independently predicted by abnormal fetal
      presentation, signs of fetal distress, toxemia of pregnancy and frequent
      antenatal visits of more than four. In addition, it is independently predicted by
      post date for primiparae and prolonged rupture of the membranes, history of still
      birth as well as previous obstetric intervention for multiparae. As for emergency
      cesarean delivery, it is independently predicted by prolonged rupture of the
      membrane, signs of fetal distress, ante-partum hemorrhage in both primiparae and
      multiparae. In addition, for primiparae, it is independently predicted by
      abnormal fetal presentation and a birth weight of more than 3500 grams while for
      multiparae, it is predicted by previous obstetric intervention as well as the non
      use of contraception following the delivery of the previous child. CONCLUSION:
      Both elective and emergency cesarean deliveries are independently predicted by
      fetal as well as maternal factors, though a proportion may not be medically
      justified considering models' predictive value. The extent of obstetric
      interventions reflects only that of specialized tertiary facility. There is a
      need for an extensive study including different level of health facilities in
      order to illustrate the whole scope of obstetric intervention and to develop a
      better understanding of its determinants.

PMID- 17219907
TI  - Studying the help seeking behavior among a group of administrative personnel in
      Theodor Bilharz Institute.
AB  - BACKGROUND: Improving the health level of the individuals requires changes in the
      behavior of the people concerned and in the structure of health service
      organization. This can be achieved by working with people to accept measures
      which will improve their health, by exploring people's health behavior, by
      providing preventive services, and by improving people's satisfaction with
      medical consultation. AIM OF THE STUDY: To provide preventive services in the
      newly established Health Education/Promotion Unit in Theodor Bilharz Research
      Institute (TBRI), relying on exploring the help seeking behavior and some related
      factors, among a group of administrative employee. SUBJECTS AND METHODS: Out of
      152 administrative employees, 80 accepted to participate, who were subjected to a
      pre-tested specially designed questionnaire soliciting information regarding help
      seeking behavior and some possible factors influencing it such as: socio
      demographic variables, knowledge about disease prevention, needed health
      information, disease perception, and some aspects of doctor patient relationship.
      RESULTS: In 80 studied administrative personnel composed of 60 (75%) females and
      20 (25%) males, with a mean age of 41.3 +/- 5.5 years, most of the participants
      were married 74 (92.5%), most of them 75 (93.8%) possessed a diploma degree in
      various administrative specialties, and nearly 2/3rd of the sample 49 (61.3%) had
      more than three children. Our study highlighted that the belief in preventive
      medicine is minimal, as only 5 (6.2%) do believe in it and male participants do
      believe more in preventive service than females (20.0% versus 1.7%, P = 0.00).
      Factors which are highly associated with the belief in preventive medicine were
      related to individual satisfaction with medical consultation (20.8% versus 0.0%,
      P = 0.00), which was mainly attributed to doctor's positive attitude towards
      their patients (13.3% versus 2.0%, P = 0.04). Illness behavior in our studied
      sample varied from going to the doctor, self treatment, and doing nothing which
      accounted for 66.3%, 25.0%, and 8.7% respectively. The only significant factor
      which affected the decision of seeking medical help was the doctor's ability to
      discuss the diagnosis with their patients (97.9% versus 18.8%, P = 0.00). Nearly
      2/3rd of the examined group reported their dissatisfaction with medical
      consultation 70%, dissatisfaction was attributed to doctor's and patient's
      attitude, which accounted for 62.5% and 37.5% respectively. CONCLUSION: Health
      care practitioners have an important role in promoting healthy behavior provided
      they have better communication skills. Understanding the help seeking behavior
      has a great reflection on the proper provision of both preventive and curative
      medicine services.

PMID- 17219908
TI  - Impact of lead exposure on health status and scholastic achievement of school
      pupils in Alexandria.
AB  - Lead exposure among children is a serious health problem affecting virtually
      every system in their bodies. Affection of their cognitive function with its
      implication of poor school performance, is one of the serious outcomes of such
      exposure. In an attempt to arrive to an adequate knowledge about the impact of
      lead exposure on the health status and scholastic achievement in school age, a
      cross sectional study was carried out on 250 primary school pupils aged from 8 to
      10 years in Wassat region in Alexandria. The concentration, visual and hearing
      acuity and the cognitive function. Moreover, laboratory investigation of blood
      lead level of the pupils was carried out. Their final scholastic achievement at
      the end of the year were recorded. The results indicated that the mean blood lead
      level among the studied pupils was 17.36 +/- 10.67 microg/dl, more than one third
      of the sample (36.00%) were highly exposed to lead with blood level of 20
      microg/dl and more. A significant negative correlation was found between blood
      lead level and the 50th percentile of weight for height (r = -0.4488),
      haemoglobin concentration (r = -0.6133) and IQ scores (r = -0.8150) of the
      pupils. While a significant positive correlation was observed with the functional
      visual and hearing loss (r = 0.1390 and 0.2189 respectively). Moreover, the
      multiple regression analysis determined that age, blood lead level, crowding
      index, IQ score and number of missed school days were the significant
      contributing variables to the final scholastic achievement of the pupils from all
      the studied factors.

PMID- 17219909
TI  - Bulimic forms of anorexia nervosa--case report no.1.
AB  - The problem remains still controversial whether anorexia nervosa and bulimia are
      disease entities or only symptom syndromes. In my patient detailed psychiatric
      examination ruled out schizophrenic process and other psychoses. It confirmed
      obsessive-compulsive syndrome. The author choosing sertraline as the basic drug
      in the treatment of the patient, took into account good therapeutic effects of
      the drug in obsessive-compulsive syndrome, reported by other authors. In the
      choice of the drug, the author of the paper followed the reports by some authors
      who obtained after sertraline body weight gain in their patients. Sertraline was
      evidently better tolerated by patients than tricyclic antidepressants. The
      cholinolytic effect of sertraline is minimal.

PMID- 17219910
TI  - Anemia in pregnancy at South Sharqiya health centers, Oman.
AB  - Despite the improvement in some indicators of maternal health, the rate of anemia
      in pregnancy in South Sharqiya Region, Oman was not satisfactory. The aim of this
      work was to study the correlates of anemia in pregnancy and its outcomes at the
      ANC clinics in South Sharqiya health centers. A health facility-based follow up
      study was designed in 1998. In randomly selected 5 health centers representing
      all wilayats of South Sharqiya Region, Oman, a form for monthly data collection
      from the ANC registers was used to follow up 852 pregnant women till their
      pregnancies ended. Hemoglobin estimation was done four times monthly apart for
      pregnant women and data was entered into the computer using EPI info program. The
      data of 852 pregnant females was analyzed where 43.6% of the sample were anemic.
      Logistic Regression showed that mother age and weight were significantly
      associated with anemia in pregnancy. Follow up of pregnant anemic women was not
      satisfactory. Anemic pregnant women showed response to iron supplement and folic
      acid received. No significant association between anemia in pregnancy whatever
      its grade and LBW or still birth. The follow-up system of anemia in pregnancy
      should be stricter. Good dietary history has to be taken from pregnant females
      for better nutritional education and to rule out unhealthy nutritional practices.

PMID- 17219911
TI  - Women empowerment and marital fertility in Oman.
AB  - International studies have the inverse relationship of women education and
      empowerment on fertility. Our aim is to study the association of women education
      and empowerment with some of fertility indicators or determinants namely; total
      number of children ever-born, age of women at her first birth and the last closed
      birth interval length in a community based survey (National Health Survey, 2000)
      A cross-sectional survey of the health status of Omani community was designed.
      Face to face interview to 2037 ever married women including demographic data,
      fertility patterns, family planning, two women empowerment indices (decision
      making and freedom of movement), and other reproductive health modules. About 31%
      of the sample was considered highly empowered in decision- making and the mean
      number of decisions taken in the household was 4.46 for the overall sample. For
      freedom of movement, 29% of the sample was highly empowered with a mean number of
      3.88 for the overall sample. The mean values of both indices varied significantly
      according to age, residence, level of education and work status. Higher freedom
      of movement score women was more likely to have less number of children in the
      first 20 years of marriage. Women of 'higher score of decision making index were
      more likely to have longer closed birth interval. Those scored low in the
      decision making index were more likely to get a child at an earlier age. In
      developing countries where fertility limitation depend on "modern" methods,
      women's education and autonomy are considered as strong tools to make changes in
      demographic transition.

PMID- 17219912
TI  - Study of serum zinc in relation to nutritional status among thalassemia patients
      in Damanhour Medical National Institute.
AB  - Thalassemia results from an imbalance between two proteins in hemoglobin called
      alpha and beta globin that interferes with cell maturation and function resulting
      in an ineffective erythropoeisis and hemolysis. Zinc is an essential element that
      supports normal growth and development. In thalassemia, the expected low serum
      zinc level is due to hemolysis, loss in urine and inadequate dietary intake. To
      evaluate serum zinc levels among thalassemia patients and study its relation to
      nutritional status and growth, a case control study was conducted at Damanhour
      Medical National Institute. Forty-six thalassemia patients were randomly selected
      from the attendants of the Hematology Unit and were compared to 20 control
      children. They were subjected to medical history and examination, anthropometric
      measurements, assessment of dietary profile, laboratory investigations for CBC,
      total serum protein, serum albumin, serum zinc. The mean age was 8.29 +/- 3.96
      years for cases and 8.45 +/- 3.52 years for controls. Thalassemia patients showed
      significant lower serum zinc level when compared to and 8.45 +/- 3.52 years for
      controls. Thalassemia patients showed significant lower serum zinc level when
      compared to control (88.28 +/- 17.76 microg/dl), and (113.5 +/- 15.39 microg/dl)
      respectively A positive correlation was found between their serum level and
      height/age (r = 0.392). Zinc supplementation and nutrition education program are
      recommended to improve growth rate among thalassemia patients with retarded
      growth ad low serum zinc levels.

PMID- 17219913
TI  - Biochemical changes and environmental factors in manual and semiautomatic
      bakeries.
AB  - The bread-making industry involves a combination of hazardous exposures. A
      biochemical and environmental study was conducted on manual and semi-automatic
      bakeries. The aim of this study was to investigate different biochemical changes
      and environmental factors among bakery workers. Blood samples were collected from
      25 exposed workers and 25 age and sex matched control subjects, determination of
      circulating IgE (immunoglobulin E), carbonic anhydrase and catalase enzyme were
      analyzed in the blood Environmental measurements (respirable dust, total
      suspended particulate TSP). Heat stress, noise and relative humidity were
      analyzed in manual and semi automatic bakeries. A significant increase in the
      level of IgE catalase and carbonic anhydrase were significantly higher among
      exposed workers in comparison with control group either in manual and semi
      automatic bakeries Environmental factors were significantly higher especially in
      manual bakeries Where higher contaminates and heat stress exposure than automatic
      ones due to nature of work type of fuel. age of oven etc and most of contaminants
      exceeded the TLV Attention should be paid to the health of the bakery workers and
      it has been recommended to completely mechanize manual bakeries.

PMID- 17219914
TI  - Biomonitoring of genotoxic risks and haematological changes in workers in rubber
      industry.
AB  - Several substances used in rubber processing are known to be of genotoxins and
      haematotoxins. Such as benzene, phenols, amines amides, naphthalene and
      benzo(a)pyrene. Twenty-five exposed workers from a rubber factory were compared
      with twenty-five controls working as administrative staff in the same factory. An
      elevated level of urinary thioether (mercapturic acid derivatives) a significant
      elevation in the level of DNA SSB was found among exposed workers in comparison
      with control group (p < 0.01). A significant increase in the absolute numbers of
      peripheral leukocytes and in erthrocyte mean cell volume was observed among
      exposed workers in comparison with controls (p < 0.01), while a significant
      decrease in the percentage of lymphocytes and eosinophils was found among exposed
      workers in comparison with controls. However, the percentage of monocytes was not
      altered. The reported results have justified the use of genotoxic biomarkers in
      assessing levels of genotoxic exposure in human population groups and as a
      screening biomarkers in periodic medical examination as a protective measure.

PMID- 17219915
TI  - Identification of causes of neonatal mortality using the ICD-10 classification: a
      study in neonatal intensive care units in Alexandria Governorate (MOHP).
AB  - In most developing countries, neonatal care has remained static or neglected for
      decades where neonatal mortality was 38/1000 live births compared to 6/1000 in
      developed countries. According to the World Health Organization (who) neonatal
      causes of death were infections (34%), asphyxia (28%), problems linked with
      preterm birth (23%) and congenital anomalies (10%). In Alexandria govemorate
      (A.R.E.) causes of death of,admitted neonates in neonatal intensive care units
      (NICU) were not recorded. The aim of the present study is to identify causes of
      neonatal deaths based on the International classification of diseases-10 (ICD-10)
      among admitted neonates in the NICU in MOHP hospitals in Alexandria so as to set
      preventive strategies to decrease the neonatal mortality. A descriptive cross
      sectional study was conducted on 2424 neonates admitted through one year (April
      2001-March 2002) in eight hospitals of MOHP. Certain modifications in the
      routinely collected monthly reports were necessary and a new computer program was
      developed in the Alexandria information center. Results revealed that hyaline
      membrane disease was the 1st cause of neonatal deaths (16.5%) followed by causes
      related to prematurity (15.8%). It was also the 1st causes of death of preterm
      neonates (27.5%). Birth asphyxia and congenital anomalies were the 1st and 2nd
      causes of death among full term neonates (21.7% each). Single dose of
      corticosteroid injection could be recommended for mothers expected to have a
      premature labor to decrease the incidence of hyaline membrane disease among
      preterm neonates.

PMID- 17219916
TI  - Biological monitoring of occupational exposure to electrophilic compound during
      rubber industry.
AB  - Electrophilic compounds are widely used in industry. Rubber processing is the
      famous example of sites where workers are exposed to electrophilic compounds.
      Besides their immediate effect on different body systems, electrophilic compounds
      include most mutagenic and carcinogenic substances. The present study was carried
      out to elucidate the possibility of using non selective assays in the biological
      monitoring of occupational exposure to electrophilic compounds. The study
      included a total number of 40 workers exposed to chemicals during rubber industry
      (n=25 exposed) and comparison group (n=15). The biochemical tests carried out on
      each subject included: (1) Estimation of thioether levels in urine as a
      biological indices of electrophilic compounds. (2) Non selective assays as
      urinary RNase and alpha esterase, glutathione-S-transferase and aryl sulphatase.
      Their determination is recommended in the biological monitoring of workers
      exposed to such agents beside the medical surveillance of workers exposed to such
      chemicals. The study finding showed significant increase in the levels of
      thioether and all the non-selective assays among exposed workers rather than the
      comparison group.

PMID- 17219917
TI  - Life style of adult diabetics of patients attending outpatient clinics.
AB  - The present study was carried out to determine the points of shortage regarding
      knowledge and lifestyle pattern of adult diabetics towards diet regimen, weight
      control, exercise, complications prevention and self management. A cross
      sectional study was conducted in two health centers in two areas, with two
      different social classes, in Helliopolis District. It included 300 the better the
      knowledge score but the practice score did not differ. The present study revealed
      that attendants to EI-Nozha and Hykstep health unit outpatient clinics had
      deficient knowledge related to diabetes management and prevention of
      complications. They also had low levels of self-care practices, which might
      adversely affect the course of the disease. The fact that knowledge affects
      behavior predicts that they will acquire higher levels self-care practices once
      they acquire sound knowledge.

PMID- 17219918
TI  - Hepatitis G virus in Egyptians infected with other parenterally transmitted
      hepatitis viruses.
AB  - A novel hepatitis-associated virus, hepatitis G virus (HGV) has recently been
      identified. The virus is known to be parenterally transmitted and has been found
      frequently in subjects chronically infected with hepatitis C virus (HCV). We
      investigated the seroprevalence of HGV infection in 91 Egyptians infected with
      hepatitis C and/or B virus including 52 patients with chronic liver disease and
      39 asymptomatic subjects. A newly developed immunoassay was used to detect
      antibody to HGV envelope protein E2. The overall prevalence of anti-HGV in study
      subjects was 34.1%. Hepatitis G virus antibody was more frequent in patients with
      chronic liver disease (36.4%-43.9%) than in asymptomatic persons (23.1%).
      Analysis of demographic features, risk factors and clinical history of the study
      population revealed that older age and history of schistosomiasis were the
      factors significantly associated with anti-HGV positivity. The study demonstrated
      that HGV is highly prevalent in individuals infected with other parenterally
      transmitted hepatitis viruses. The impact of such observation rises in view of
      the endemicity of hepatitis C and B viruses in Egypt.

PMID- 17219919
TI  - A high hepatitis E virus (HEV) seroprevalence among unpaid blood donors and
      haemodialysis patients in Egypt.
AB  - BACKGROUND/AIMS: The aim of this study was to determine the frequency of
      hepatitis E virus (HEV) infection among unpaid blood donors and haemodialysis
      patients in Egypt and to find out any possible relationship between HEV and HCV.
      METHODS: Serum samples collected from 95 unpaid blood donors and 96 haemodialysis
      patients were screened for HEV and HCV antibodies by enzyme immunoassay
      techniques. RESULTS: The prevalence of anti-HEV IgG was 45.2% (43/95) in blood
      donors and 39.6% (38/96) in haemodialysis patients. Anti-HEV IgG was found in
      69.2% (18/26) and 28.6% (20/70) in haemodialysis patients positive and negative
      for HCV, respectively. CONCLUSION: This study emphasizes that HEV is endemic in
      Egypt and tends to accumulate in certain groups showing evidence of hepatitis C
      virus infection as in haemodialysis patients suggesting either shared parenteral
      risk or increased sensitivity to HEV coinfection; that is to say a possibility of
      combined route of transmission for HEV.

PMID- 17219920
TI  - Prevalence of certain sexually transmitted viruses in Egypt.
AB  - The magnitude of Sexually Transmitted Diseases (STD) in the Eastern Mediterranean
      Region is not exactly known but considered to be not insignificant. A realistic
      estimate of the problem is necessary, to design an effective control program.
      This present study aimed to identify the most prevalent sexually transmitted
      viral agents among patients attending the STD clinic at Cairo Hospital for Skin
      and Venereal Diseases (El-Haud El-Marsoud). From persons attending this clinic
      whether complaining or visiting for screening, between October 1993 to April
      1995, 95 cases were studied by history taking, clinical examination,
      bacteriological and serological examination for the detection of the most
      prevalent sexually transmitted organisms. Certain demographic and socio-economic
      factors interacting with sexual attitudes and practices were also studied. All
      the collected data for each patient were recorded. Antibodies (IgG) to
      cytomegalovirus (CMV) were detected in 86.3%, HBsAg in 10.5%, and antibodies to
      HBcAg were detected in 45.3%. Antibodies to HCV were detected in 8.4%, and
      antibodies to HIV in 5.3%.

PMID- 17219921
TI  - The application of the hazard analysis and control points (HACCP) in an ice cream
      production plant.
AB  - The HACCP system is applied in the present study as a preventive food safety
      approach to control some hazards appearing in one of the ice cream production
      plants in Egypt. The problem comprised the presence of bacteriological and some
      chemical contamination in most of the company products. Before applying the HACCP
      system, the samples examination showed high total mesophilic plat count in 50% of
      the samples and high coliform count in all samples compared to the level
      recommended in the Egyptian standards. The highest staphylococcal count (negative
      for coagulase test) obtained was that of chocolate (1.3 x 10(4) CFU/g) followed
      by mango ice cream (l.0 x 10(4) CFU/g). Faecal coliform was only positive in
      mango ice cream. Additionally, the levels of lead, iron and copper have been
      determined. Copper was higher than the recommended level in all samples and
      ranged between 0.46 ppm in pistachio ice cream and 2.48 ppm in chocolate ice
      cream. Most of the CCPs in the ice cream production were mainly due to improper
      handling and practices throughout the processing steps and also related to the
      lack of food hygiene knowledge of the workers. The application of HACCP system
      has successfully reduced the bacteriological hazards in all samples. After
      applying the corrective actions, the highest total aerobic plate count (8.0 x
      10(4)) was that of Swiss chocolate ice cream which corresponds to 50% of the
      recommended level by the Egyptian standards. Coliform count was less than 10 in
      all samples except mango ice cream (43 MPN). A significant decrease in
      staphylococcal count, faecal coliform and trace metal contamination was also
      recorded in all samples.

PMID- 17219922
TI  - Schistosomes as parasites of man and animals.

PMID- 17219923
TI  - Prevalence of rheumatic heart disease among school children in Alexandria, Egypt:
      a prospective epidemiological study.
AB  - The aim of this work was to study the epidemiologic features of Rheumatic Heart
      Disease (RHD) among basic education students in Alexandria, including the
      demographic and clinical profiles as well as risk factors for RHD development. A
      stratified random sampling technique was used to allocate 5465 school children in
      the six educational zones of Alexandria. Clinical RHD cases were confirmed by
      using chest X-ray, ECG and echocardiography. Factors related to occurrence of RHD
      were studied using a case control design. Thirty four RHD cases (with an
      estimated prevalence of 6.2/1000 students) were diagnosed. Low socioeconomic
      status, chronic tonsillitis, positive family history of acute rheumatic fever/RHD
      and paternal consanguinity were significantly associated with the occurrence of
      RHD. Almost all previously diagnosed cases were enrolled in a prophylaxis
      program, with a defaulter rate of 31%. More than half of the identified cases had
      moderately severe valvular lesions. We recommend the implementation of an
      educational program targeted to both parents and teachers; the training of
      upgrading of school health physicians, and the standardization of secondary
      prophylaxis programs nationwide, with emphasis on assurance of compliance.

PMID- 17219924
TI  - Personal factors and working conditions as predictors of work injuries among
      industrial workers.
AB  - The purpose of this study was to determine the personal factors and working
      conditions that predict work injuries among industrial workers. To fulfill this
      aim, a case control study was conducted including 2003 industrial workers who
      sustained a work injury and an equal number of controls. All were subjected to an
      interview questionnaire to collect relevant information. Moreover, records were
      reviewed to obtain the medical history of enrolled workers. Data revealed that
      workers in the index and control groups are comparable in respect to their
      sociodemographic characteristics. The multivariate logistic regression analysis
      pointed out that safety training significantly reduces the risk of work accidents
      among industrial workers. On the other hand, work accidents are more likely to
      occur in the main working shift. Moreover, workers who suffer from chronic health
      problems calling for surgical treatment, as well as those who reported family
      problems, are more likely to experience work accidents. These workers should
      receive considerable attention to reduce the extent of work injuries. More
      importantly, safety-training programs are mandatory for accident prevention in
      industrial settings.

PMID- 17219925
TI  - Health status assessment of drug addicts in Alexandria.
AB  - The case-control study was conducted among addicts in Alexandria to determine the
      different health problems among them, as well as to study the correlation between
      addiction and these problems. One hundred drug addicts and eighty apparently
      healthy controls were included in this study. The whole sample was subjected to
      the following: filling a predesigned questionnaire sheet, clinical and
      electrocardiogram (ECG) examination, measurements of Body Mass Index (BMI),
      complete blood picture and antistreptolysin O titre (ASO), testing for hepatitis
      B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti HBc),
      skin scrapings from superficial fungal lesions in addition to complete urine and
      stool examination. The results revealed that chest rhonchi, hepatomegaly, central
      nervous system (CNS) abnormalities, skin lesions lymphadenopathy, underweight and
      anaemia were significantly higher among addicts than the controls. Hepatitis B
      virus (HBV) exposure and HBsAg seropositivity were found 48.0% and 21.0%,
      respectively among addicts compared to 26.3% and 5.0%, respectively among the
      controls. The intravenous injections and tattooing were the most risky routes for
      HBV infection among addicts. A positive correlation was revealed between HBV
      exposure and both the duration and the number of daily injections. Chest X-ray
      suggestive of pulmonary tuberculosis were found in 7.0% of the addicts. Addiction
      potentiated the risk of fungal infection among low social class, but it had no
      effect on the relationship between anaemia and social class nor on that between
      loss of appetite and underweight.

PMID- 17219926
TI  - Sister chromatid exchanges and chromosome aberrations in lymphocytes of medical
      personnel handling cytostatic drugs.
AB  - Many anticancer drugs, including cytostatic drugs, are genotoxic. Evidence on
      human carcinogenicity has been conclusive. Persons handling these drugs might be
      exposed to an occupational health hazard, as they cause chromosomal damage in the
      lymphocytes. This study was conducted on 30 Egyptian medical personnel handling
      cytostatic drugs, working in the Medical Research Institute, Alexandria
      University and Gamal Abd El Naser Hospital in Alexandria. A control group
      comprised 30 normal healthy individuals matched for age and sex and had no
      contact with cytostatic drugs. Also, they were not exposed to any mutagenic
      agents. The workers and controls were interviewed to exclude exposure to any
      mutagenic agents other than anticancer drugs in case of medical workers.
      Cytogenetic methods were done to all subjects to assess chromosomal aberrations
      (CA) and sister chromatid exchanges (SCE). Significantly increased frequencies of
      CA and SCEs were found in exposed personnel as compared to the controls.
      Chromosomal aberrations and SCEs frequencies were not correlated with the age of
      exposed personnel and duration of exposures to cytostatic drugs. There was no
      increased risk of malformed children in exposed females and no history of
      repeated abortion. The results of this study point to the handling of cytostatic
      drugs as a possible genotoxic hazard. Therefore, effective protection and care in
      handling must be further emphasized to prevent adverse effects.

PMID- 17219927
TI  - Quality assessment of medical care in chest dispensaries in Alexandria.
AB  - Eight million new cases of tuberculosis are merging annually, worldwide, of which
      an estimated three million are dying. The quality of medical care rendered by
      chest clinics (dispensaries) to tuberculous patients is crucial. The present
      study was conducted in order to assess quality of medical care rendered to
      tuberculous patients in all chest clinics in Alexandria (n=7). To achieve this
      aim, three checklists were developed in relation to the three dimensions of
      medical care, namely, structure, process of care and outcome. They were validated
      and rated by ten medical experts working in the field of tuberculosis and chest
      diseases. Accordingly for the process of care, each item was scored using
      weighted scores for physicians' performance. Unit weighted scoring was also used
      for physicians, nurses, as well as social workers. Direct observation was
      conducted for assessment of structure and process of care rendered by physicians,
      nurses and social workers. On the other hand, outcome was measured by cure or
      treatment completion rate, treatment failure rate, defaulter rate, as well as
      death rate. The results revealed that percentage of recommended structure items
      ranged between 77.8% and 94.4%. Regarding process of care, it was found that the
      overall weighted physicians' performance index (PPI) expressed in percentage was
      36.97+/-13.65%, while the mean unit weighted PPI was 35.26+/-13.5%. For the
      different areas of care, the mean weighted and unit weighted PPI, respectively,
      were 27.86+/-20.83% and 28.6+/-21.7% in history taking, 54.65+/-11.92% and
      42.83+/-13.83% for examination, 31.64+/-19.61% and 37.10+/-19.40% for educating
      patients, while it was 36.36+/-16.0% and 37.90+/-16.20% for measures applied to
      contacts. Moreover, assessment of nurses and social workers' performance revealed
      that they had carried out 91.86% and 86.60% of their recommended activities,
      respectively. Outcome indices among the different clinics showed that cure or
      treatment completion rate ranged from 47.48% to 81.51%, while treatment failure
      rate ranged between 1.71% and 11.54%. On the other hand, the defaulter rate
      showed a minimum of 13.70% and a maximum of 44.86%. From the present study it
      could be recommended that quality of medical care in chest clinics should be
      emphasized specially as regards process of care given by physicians.

PMID- 17219928
TI  - Sanitation characteristics of some food processing industries.
AB  - The present investigation was carried out to evaluate the sanitary conditions
      surrounding the food throughout the production stages in some food plants.
      Observation of the sanitary measures of the studied plants revealed that only 3
      out of the 7 plants (42.9%) have acceptable sanitation that complies with the
      sanitary requirements specified by WHO. Personal hygiene and storage conditions
      were the most critical problems found in the studied plants. Laboratory
      examination of nasal and throat swabs and stool samples of workers was carried
      out to uncover the chronic carriers. Among the food handlers examined 46.3% were
      positive for intestinal parasites. Bacteriological examination of stool specimens
      revealed that 4.3% of carriers of Salmonella paratyphi and none were carriers of
      Vibreo species. Nasal swabs were also positive for Staph. aureus in 29.8% of all
      the examined swabs. Analysis of the main products of the studied plants revealed
      generally that the bacterial load of the products of plants having acceptable
      sanitary conditions was lower than that of the products of the other plants. The
      frozen vegetable products had a total aerobic mesophilic plate count ranging from
      8.1 x 10(4) cfu/g in okra and 3.7 x 10(5) cfu/g in mixed vegetables. The total
      aerobic plate count of the ice cream (1 x 10(3) cfu/g) complies with specified
      Egyptian standards. However, the coliform count (9 x 10(1) MPN) was higher than
      the recommended limit. Lead and cadmium levels were also investigated in all
      products. The maximum detected level of lead was that of cream wafer (0.94 ppm)
      followed by banana wafer (0.82 ppm). The two detected levels were higher than
      Egyptian standards. The lead level in ice cream (0.19 ppm) was also higher than
      the specified standards. The relatively high levels of lead in cream wafer and
      ice cream may be attributed to more than one factor; the added color and the old
      machinery used in some production steps are the most accursed factors. On the
      other hand, the observed level of cadmium ranged between 0.046 ppm in raw mil and
      0.3 ppm in soft cheese.

PMID- 17219929
TI  - Abdominal ultra sonographic findings detected in the course of a hepatitis survey
      in an Egyptian rural area.
AB  - The objective of this study was to determine the prevalence of abnormal findings
      detected by abdominal ultrasonography (US) in an Egyptian rural area. This study
      was a part of a community based cross sectional survey for virus hepatitis
      carried out at Kalama village in Nile Delta, 40 kilometers north of Cairo. People
      above 10 years of age living in a 10% systemic random sample of houses in the
      village were subjects of this study. A member of the team carried out US
      examination of the liver, biliary tree, spleen, kidneys, pancreas, para aortic
      areas and the pelvis. Examination included morphological assessment and
      organometry. All results are recorded on images by videoprinter. Abnormalities in
      abdominal US was detected in 34% of examined cases. Abnormal liver impressions
      were detected in 28.3% of cases. Ascites was detected in 13 cases (1.8%).
      Diseases of the gall bladder and kidneys were detected in 2.7% and 2.1%,
      respectively. US diagnosed pregnancy in 5 women, one of them had a blighted ovum.
      Some of these abnormalities were detected in subjects with no complaint. It is
      concluded that abdominal US may be a tool for early detection of asymptomatic
      disease.

PMID- 17219930
TI  - Manufacture and characterization of an air pollutants' adsorbent from agrowastes.
AB  - The by-products of some agricultural industries and activities might perform a
      problem as regards to their disposal. The present study is devoted to make a good
      use of these wastes and consequently, the solution of the disposal problem. The
      results of activation and characterization of date stones, residual cake after
      squeezing olive oil and charcoal are presented in this study. These preliminary
      results, which are based on original, simple and accelerated characterization
      criteria, reveal the validity of the used precursors to produce air pollutants'
      adsorbent.

PMID- 17219931
TI  - Assessment of students' knowledge, attitude and practice concerning cancer and
      its prevention. Part I.
AB  - Cancer is a serious public health issue, but it is increasingly regarded as
      preventable. The present study was conducted to assess students' knowledge,
      attitude and practice about cancer. A questionnaire was developed by the
      researchers and completed by 896 secondary school students from the middle zone
      of Alexandria Governorate. Females had a significantly higher awareness than
      males as regards the relationship between not eating vegetables and fruits,
      environmental effects, exposure to irradiation or to the sun for long periods and
      the hazards of getting cancer. Third grade students were significantly more
      knowledgeable than the other two grades (H=11.43, p<0.01). Only 4.5% of the
      participants had satisfactory levels of knowledge. Students in general expressed
      strong fear of cancer. Females were more worried than males either about
      themselves getting cancer or about others having it. More than 50% of the females
      liked to be friendly with children having cancer as compared to 37% of males.
      Only 12.3% of the students had a positive attitude towards cancer prevention.
      Males tended to consume healthier foods than females. Furthermore, 57% of the
      students demonstrated good practice. School education on cancer is extremely
      needed for these adolescents in order to correct misconceptions, provide accurate
      information and to develop a positive attitude towards cancer.

PMID- 17219932
TI  - Symptom experience and emotional distress after traumatic brain injury.
AB  - Traumatic brain injury (TBI) is unexpected and affects nearly 1.5 million
      Americans annually. Many with seemingly minor injuries incur long-lasting
      symptoms without clear explanation. This study examined the symptom experience
      and emotional response of persons with mild-to-moderate TBI and was guided by the
      University of California San Francisco (UCSF) symptom management model. Using a
      cross-sectional design with persons recruited from outpatient rehabilitation
      settings, we found a positive and significant relationship between postinjury
      symptom frequency and tension/anxiety, anger/hostility and perceived chronic
      stress, implying a need to understand these relationships over time in order to
      implement symptom management strategies.

PMID- 17219933
TI  - Medicare drug coverage 101: everything you need to know about the new Medicare
      prescription drug benefit.

PMID- 17219934
TI  - We create the path by walking: Maryknoll Sisters health care--long-term care.
AB  - Religious groups like the Maryknoll Sisters have been examining their
      demographics for years and seeking ways to deal with the aging of their
      communities while facing diminishing numbers of new members. In 1999, the Sisters
      projected that in the year 2010, they would number 447, and 359 of them would be
      over the age of 65 years; 228 would be over the age of 75! Each Sister and the
      Maryknoll community as a whole deal with aging using the strengths of their
      lifestyle, spirituality, and support systems. They have learned that they must
      discern their future with a notion inspired by St. Augustine, "solvitur
      ambulando,"--it is solved by walking. This article considers one religious
      community's approach to long-term care at the beginning of the 21st century using
      personal stories and highlighting some of the options the Maryknoll Sisters have
      developed.

PMID- 17219935
TI  - Palliative care/physician-assisted dying: alternative or continuing care?
AB  - End-of-life care for dying patients has become an issue of importance to
      physicians as well as patients. The debate centers around whether the option of
      physician-assisted suicide cuts off, or diminishes the value of palliative care.
      This ongoing attention makes the crafting of advance directives from patients
      detailing their end-of-life choices essential. Equally important is the
      appointment of a health care surrogate. The surrogate, when the patient is too
      ill to make decisions, should be empowered to make them in his stead. No American
      court has found a clinician liable for wrongful death for granting a request to
      refuse life support. An entirely separate issue is that of legalized physician
      assisted suicide. As of this writing, only Oregon has made this legal (see
      Gonzales v. Oregon). It is likely that this issue will be pursued slowly through
      the state courts, making advance directives and surrogacy all the more crucial.

PMID- 17219936
TI  - The University of New Mexico Visiting Physicians Program: helping older New
      Mexicans stay at home.
AB  - New Mexico is a rural state with unique barriers to health service delivery to
      homebound elderly. The University of New Mexico's Visiting Physicians Program
      allows these patients to stay in their homes by bringing physicians to them. The
      physicians use community agencies to provide nursing, lab, X-ray, and physical
      therapy services. The University of New Mexico has also integrated home visits
      into the medical students, residents and geriatric fellows' educational programs.
      By involving medical students, residents and fellows in home care, future
      physicians who practice in New Mexico will incorporate this valuable service into
      care for the homebound elderly in their practice communities.

PMID- 17219937
TI  - The process of ethical decision making.
AB  - This chapter discusses a framework for and process of ethical decision making in
      the context of the discipline, theories, and principles of ethics. Daily decision
      making within the Hospital Ethics Committee is considered and some of the
      emerging ethical issues in anaesthesia are discussed.

PMID- 17219938
TI  - Informing and consenting for anaesthesia.
AB  - Public expectations of healthcare have changed dramatically over the last 10-20
      years, particularly in relation to the involvement of patients in determining
      treatment options and the selection of the most appropriate treatment plan.
      Paternalistic actions of doctors, which involved telling the patient what
      treatment they were going to receive, without discussing risks and benefits of
      various options, are no longer acceptable. This has been reflected in decisions
      reached by the courts in cases in which patients have entered litigation on the
      basis that inadequate information was given to them before treatment, and that
      they were unaware of risks of complications which subsequently materialised. If
      such claims are successful, the patient is entitled to financial compensation
      even if the treatment was carried out to the highest standard. Although most
      claims of this nature are brought against surgeons, similar claims are likely in
      relation to anaesthetic procedures. Complaints about lack of information or
      inadequate consent can also result in a doctor being reported to regulatory
      authorities. It is therefore necessary for anaesthetists to be aware of current
      issues surrounding provision of information and obtaining consent for anaesthesia
      in various categories of patient. This article summarises these issues.

PMID- 17219939
TI  - Confidentiality, 'no blame culture' and whistleblowing, non-physician practice
      and accountability.
AB  - Confidentiality is a core tenet of medical professionalism, which enables the
      maintenance of trust in a doctor-patient relationship. However, both the amount
      of personal data stored and the number of third parties who might access this
      data have increased dramatically in the digital age, necessitating the
      introduction of various national data protection acts. Paradoxically, the Freedom
      of Information Act 2000 allows United Kingdom citizens to access information held
      by public bodies, including hospitals. Furthermore, the Public Interest
      Disclosure Act 1998 actively protects physicians who breach their duty of
      confidentiality in the name of public interest ('whistleblowing'). This article
      explores the evolution of the law and ethics in this area, and draws attention to
      the difficulties in balancing confidentiality against freedom of information. In
      addition, the role and responsibilities of the non-physician anaesthetist are
      examined.

PMID- 17219940
TI  - Patients who challenge.
AB  - Individuals have different values. They seek to express their individuality even
      when receiving medical care. It is a part of modern medical practice and respect
      for patient autonomy to show respect for different values. We give an account of
      what it means to respect different values and challenging patients in medical
      practice. Challenging choices are often choices which are perceived by many to be
      either irrational or against a person's interests, such as engaging in harmful or
      excessively risky activities. When the medical profession is involved in such
      choices, the basic medical principle of acting in a person's best interests is
      challenged. Often doctors refuse to respect controversial choices on
      paternalistic grounds. We should all respect and facilitate the controversial
      choices of competent individuals, subject to resource limitations, our own and
      others well-being and autonomy, and the public interest. But more importantly,
      sometimes such choices make for a better, more autonomous life. Sometimes, such
      choices reflect considerations of global well-being or altruism, or idiosyncratic
      attitudes to risk. Sometimes, they reflect unusual values. However, in some other
      cases, controversial choices are irrational and are not expressions of our
      autonomy. Doctors should assist patients to make rational if individual choices.
      The patient also bears the responsibility for bringing his beliefs to the
      attention of the clinician.

PMID- 17219941
TI  - The pregnant and the parturient.
AB  - Society and the culture of health care delivery have radically changed over the
      last thirty years, the rate of change increasing exponentially towards the
      present time. Maternity care has been part of that change. Previously
      paternalistic obstetricians told women whether they should or should not become
      pregnant, advised hospital confinements, kept women in hospital for days after
      their confinements, and discussed little of their management with the women
      themselves. Now women have choice and they exercise that choice. There is choice
      as to the kind of antenatal care women wish to have, where they will deliver
      their baby and who will look after them during their pregnancy and delivery. This
      was, and to a certain extent still is, threatening to obstetricians. But there
      are also genuine concerns as to whether these changes will adversely influence
      the morbidity and mortality of mother and child. This chapter deals with issues
      of maternal choice from pre conception through to the post natal period, looking
      at how the exercise of maternal choice may conflict with the advice of the
      medical profession, potentially leaving accountability and responsibility a very
      grey area and how all this impinges on the anaesthetist.

PMID- 17219942
TI  - Limiting and rationing treatment in paediatric and neonatal intensive care.
AB  - In this chapter I consider the ethical decisions surrounding the provision and
      limitation of treatment offered to children requiring intensive care. I focus on
      the processes surrounding end of life decision making and consider how the
      concepts of futility, burden and uncertainty should impact upon these decisions.
      I also examine resource allocation to children's critical care services. The
      discussion does not provide a structure that will solve any given situation. It
      does take a practical approach to the issues faced by considering why we should
      engage in life limiting discussions; When they should occur; Who should be
      involved; How they should be carried out; and where and by what means withholding
      or withdrawal should occur. I have drawn the discussions closer to clinical
      practice with the intention of making them more useful, for those engaged in
      direct patient care, than those focused around philosophical principles.

PMID- 17219943
TI  - Ethics and law in the intensive care unit.
AB  - Intensive Care Medicine epitomises the difficulties inherent in modern medicine.
      In this chapter we examine some key medicolegal and ethical areas that are
      evolving. The principles of autonomy and consent are well established, but
      developments in UK caselaw have shown that the courts may be moving away from
      their traditional deference of the medical profession. We examine some recent
      cases and discuss the impact that these cases may have on practice in Intensive
      Care.

PMID- 17219944
TI  - Recent thinking about end of life issues.
AB  - Frequently, ethical dilemmas for clinicians in ICU focus on the conflict between
      the sanctity of life principle and other important ethical principles, such as
      patient autonomy or quality of life. Therefore, this chapter seeks to reveal the
      ethical tension between the sanctity of life and other competing ethical
      obligations, clearly outlining how the law in reality is making decisions and
      what a clinician's duties are in end of life issues.

PMID- 17219945
TI  - Trainee and training issues.
AB  - This chapter deals with the obligations of trainers and trainees to each other,
      the responsibilities of the programme and the conflicts of providing a service
      while training. Management of trainees with differing needs, such as those
      working part-time or returning to training after sickness, is reviewed.
      Assessment of performance and the obligation of consultants to identify, manage
      and support struggling trainees are discussed. Ethical discussion is based on the
      principles of autonomy, non-maleficence, beneficence, and justice to which
      fidelity is added. Case studies illustrating the application of ethical
      principles to work and decision-making are presented to stimulate debate.
      Opinions vary as to which principle carries more weight in individual cases, and
      how best to balance the conflicting requirements of the parties involved
      (patient, trainee,.trainer, employer, society). For all healthcare practitioners,
      the needs of patients remain our first concern. Acting in a consequentialist way,
      we must "maximise the good" and minimise the attendant harms in training.
      However, deontology states that certain sacrosanct rules and principles should
      never be breached. Doctors must abide by the duties of a doctor described in Good
      Medical Practice, maintaining standards in a way that ensures professional
      qualifications are respected. For the patient, there are advantages and
      disadvantages to receiving care in an educational setting. A 'teaching
      environment' tends to encourage and maintain high standards of practice from
      senior clinicians, but it also exposes patients to new learners, who are less
      efficient and polished and perhaps more prone to make errors. Learning has to fit
      round and complement the clinical and emotional needs of patients.

PMID- 17219946
TI  - Substance abuse and dependence in anaesthetists.
AB  - The incidence of substance abuse amongst anaesthetists in the United Kingdom is
      unknown. In the interests of patient safety, it is essential that the dependent
      doctor is identified and entered into a treatment regime. No national strategy is
      in place to treat and, where possible, return the anaesthetist in recovery to
      work. It is important therefore, that individual employers have a standing
      operating procedure to deal with the addicted doctor. It is essential that the
      initial approach is made by a competent panel, each of whom has experience of
      dealing with dependent doctors. This is an extremely stressful time for the
      doctor involved; it is therefore essential that active support is given. It is
      not always necessary to suspend the doctor from work whilst treatment is
      undertaken. In the dependent doctor sudden withdrawal of the substance of
      addiction can be life-threatening. It is therefore essential that the supervising
      physician has specialist knowledge of the treatment of addiction. Residential
      care probably provides the greatest hope of success. In the United States,
      Canada, Australia and New Zealand 'impaired physician' programmes are in place
      which allow some doctors to return to work, initially under strict supervision.
      Registration with a self-help organisation is essential; a list of such groups in
      the United Kingdom is appended.

PMID- 17219947
TI  - The older anaesthetist.
AB  - It is not possible to generalise about the way in which increasing years affect
      the performance of an individual anaesthetist. Physical and mental deterioration
      occurs as we age; most anaesthetists will be able to reach the normal retirement
      age of 65 years without that deterioration affecting their clinical practice. In
      some, however, decreasing competence and an unwillingness to embrace a continuing
      education regime may offer a direct threat to patient safety. Stress and
      'burnout' are common in anesthetists; clinical depression can often be one of the
      factors involved. Continuing involvement in the on-call rota is a potent
      stressor. Airline pilots are required to retire at 60 years; the feasibility and
      desirability of applying this process to anaesthetists are discussed. Employers
      have a duty to provide employees with adequate and achievable demands in relation
      to their agreed hours of work and to have in place policies and procedures to
      offer adequate support.

PMID- 17219948
TI  - Research audit and publication.
AB  - The ethics of research, audit and publication have developed mainly within the
      last fifty years. The Declaration of Helsinki is the universally accepted code of
      conduct for researchers worldwide. All research has to be approved by an ethics
      committee, all of which are governed by a centralised structure which is the
      Central Office for Research Ethics Committees (COREC) in the UK. This
      standardised system has been developed to oversee all research activity across
      the whole of Europe and every European county will have an equivalent
      organisation. The committees concern themselves with research but the differences
      between audit and research are difficult to discern in many places. If there is
      any doubt then the advice of the local research ethics committee should be
      sought. Only the individual him/herself can give consent. This may produce
      difficulties in cases of certain groups especially unconscious patients and
      children. The outcome of every study should be published whatever the results and
      the ongoing development of centralised (national) research trial databases will
      promote this philosophy. Publication of results thought to be of lesser
      importance may prove difficult, however, and so there is a temptation to falsify
      or modify data to make it more attractive. This, together with other activities
      such as the fabrication of data, plagiarism, dual publication, salami
      publication, conflicts of interest and irregularities in authorship, have given
      Editors of journals a number of problems. Many of these issues around publication
      ethics may prove difficult to detect but the fear of sanctions from employers and
      professional organisations is a useful deterrent.

PMID- 17219949
TI  - Construction and expression of bivalent membrane-anchored DNA vaccine encoding
      Sjl4FABP and Sj26GST genes.
AB  - In order to construct a eukaryotic co-expression plasmid containing membrane
      anchored Sjcl4FABP and Sjc26GST genes and identify their expression in vitro,
      Sj14 and Sj26 genes were obtained by RT-PCR with total RNA of Schistosoma
      japonicum adult worms as the template and cloned into eukaryotic expression
      plasmid pVAC to construct recombinant plasmids pVAC-Sj14 and pVAC-Sj26. Then a 23
      amino-acid signal peptide of human interleukin-2 (IL-2) upstream Sj14 or Sj26
      gene and a membrane-anchored sequence containing 32 amino-acids of carboxyl
      terminal of human placental alkaline phosphatase (PLAP) downstream were amplified
      by PCR as the template of plasmid pVAC-Sj14 or pVAC-Sj26 only to get two gene
      fragments including Sj14 gene and Sj26 gene. The two modified genes were
      altogether cloned into a eukaryotic co-expression plasmid pIRES, resulting in
      another new recombinant plasmid pIRES-Sj26-Sj14. The expression of Sj14 and Sj26
      genes was detected by RT-PCR and indirect immunofluorescent assays (IFA) when the
      plasmid pIRES-Sj26-Sj14 was transfected into eukaryotic Hela cells. Restriction
      enzyme analysis, PCR and sequencing results revealed that the recombinant
      plasmids pVAC-Sj14, pVAC-Sj26 and plRES-Sj26-Sj14 were successfully constructed
      and the expression of modified Sj14 and Sj26 genes could be detected by RT-PCR
      and IFA. A bivalent membrane-anchored DNA vaccine encoding Sj14 and Sj26 genes
      was acquired and expressed proteins were proved to be mostly anchored in cellular
      membranes.

PMID- 17219950
TI  - Construction of human ScFv phage display library against ovarian tumor.
AB  - In order to construct a single chain fragment variable (ScFv) phage display
      library against ovarian tumor, by using RT-PCR, the human heavy chain variable
      region genes (VH) and light chain variable region genes (VL) were amplified from
      lymphocytes of ovarian tumor patients and subsequently assembled into ScFv genes
      by SOE. The resulting ScFv genes were electrotransformed into E. coli TG1 and
      amplified with the co-infection of helper phage M13KO7 to obtain phage display
      library. The capacity and titer of the resulting library were detected. The phage
      antibody library with a capacity of approximately 3 x 10(9) cfu/microg was
      obtained. After amplification with helper phage, the titer of antibody library
      reached 5 x 10(12) cfu/mL. Human ScFv library against ovarian tumor was
      constructed successfully, which laid a foundation for the screening of ovarian
      tumor specific ScFv for the radioimmunoimaging diagnosis of ovarian tumor.

PMID- 17219951
TI  - Inhibition of RAW264.7 macrophage inflammatory cytokines release by small hairpin
      RNAi targeting TLR4.
AB  - In order to construct an expression vector carrying small hairpin (sh) RNA
      (shRNA) for toll-like receptor 4 mRNA and a reporter gene of enhanced green
      fluorescence protein (EGFP) and study the inhibition of cytokine release by
      RAW264.7 cell induced by lipopolysaccharide (LPS) stimulation through
      transfection and expression of shRNA targeting TLR4 gene via the RNAi mechanism,
      the reporter gene plasmid pEGFP-C1 (4.7 kb) and psiRNA-hHlneo (2979 bp) were
      used. The H1 promotor and double Bbs I restrict endoenzyme site were cloned from
      plasmid psiRNA-hH1neo and reconstructed them into plasmid pEGFP-C1 in the Mlu I
      restrict endoenzymic site, forming plasmid pEGFP-H1/siRNA, which contained Bbs
      site and reporter EGFP gene. Then an oligonuclear hairpin sequence targeting TLR4
      gene was designed by internet tool and inserted into the plasmid pEGFP-H1/siRNA
      forming plasmid pEGFP-H1/TLR4-siRNA. After transfection of pEGFP-H1/TLR4-siRNA
      into RAW264.7 cells, tumor necrosis factor-alpha (TNF-alpha) release by the cells
      after stimulation by LPS was detected. The results showed that the constructed
      pEGFP-H1/TLR4-siRNA carrying hairpin RNA for TLR4 gene and reporter EGFP gene
      were proven to be right by restriction endonuclease analysis. The expression of
      EGFP gene was (50.37+/-8.23) % and after transfection of the plasmid pEGFP-H1/
      TLR4-siRNA the level of TNF-alpha released by RAW264.7 cell was down regulated.
      It was concluded that shRNA targeting TLR4 gene could inhibit the TNF-alpha
      release by RAW264.7 cells evoked by LPS.

PMID- 17219952
TI  - Expression of survivin in human non-Hodgkin lymphoma and its correlation with
      proliferation and angiogenesis.
AB  - In order to investigate the expression change of survivin in non-Hodgkin lymphoma
      (NHL) and its possible effects on NHL development, the expression of survivin, Ki
      67, caspase3 and FVIIIRAg in reactive lymphoid hyperplasia (RH) and NHL was
      detected by immunohistochemical assay, and apoptosis index (AI) in RH and NHL by
      TUNEL analysis. The results showed that the expression of survivin is
      significantly higher in aggressive NHL than in indolent NHL (P<0.01), while there
      was no statistically significant difference between RH and indolent NHL (P>0.05).
      The expression of survivin had a significantly positive correlation with the
      expression of Ki-67 and FVIIIRAg (r=0.6495, 0.6635, respectively, both P<0.01),
      and a negative correlation with the expression of caspase3 and AI (r=-0.5820, 
      0.6013, respectively, P<0.01). It was suggested that survivin may contribute to
      the progression of NHL by playing an important role in promoting cell
      proliferation, inhibiting cell apoptosis and enlisting angiogenesis. Survivin
      expression is closely related to malignant grade and therefore may be considered
      an important prognostic factor of NHL.

PMID- 17219953
TI  - Low-dose ATRA supplementation abolishes PRM formation in rat liver and
      ameliorates ethanol-induced liver injury.
AB  - The effects of all-trans-retinoic acid (ATRA) in low doses supplementation on
      concentrations of polar retinoid metabolites (PRM) and retinoids in the ethanol
      fed rat liver, and on hepatocyte injury were investigated. The rat model of
      alcoholic liver disease (ALD) was induced by intragastric infusion of ethanol,
      and then the rats were administrated with ATRA in two different doses (150
      microg/kg body weight and 1.5 mg/kg body weight) for 4 weeks. Concentrations of
      retinoids in rat liver and plasma were determined by using HPLC. Liver tissues
      pathologic changes were observed under the light microscopy and electron
      microscopy. The serum transaminases concentrations were measured. The results
      showed that the HPLC analysis of retinoids revealed that retinoids (vitamin A,
      RA, retinyl palmitate) concentrations in ethanol-fed rat liver and RA
      concentration in ethanol-fed rat plasma were markedly diminished (P<0.01) after
      ethanol feeding for 12 weeks. Furthermore, obvious peaks of PRM were formed in
      livers of ethanol-fed rats. ATRA 150 microg/kg supplementation in ethanol-fed
      rats for 4 weeks raised RA concentration in both liver and plasma, and also
      raised vitamin A concentration in liver to control levels, partially restored
      retinyl palmitate concentration (P<0.05) in liver. ATRA 1.5 mg/kg supplementation
      raised not only RA concentrations in liver and plasma but also retinyl palmitate
      concentrations in liver. However, the vitamin A concentration in liver of ATRA
      supplemented rats (1.5 mg/kg) was higher than that of controls (P<0.05). The
      histologic observation of liver tissues indicated that ATRA treatment notably
      alleviated hepatocellular swelling, steatosis, the swelling of mitochondria and
      proliferation of smooth endoplasmic reticulum (SER). ATRA treatment greatly
      decreased levels of serum transaminases as compared with the only ethanol-fed
      group (P<0.05). It was concluded that low-dose ATRA treatment could restore
      retinoids concentrations and abolish the PRM formation in liver of ALD rats, and
      then ameliorate the injury of liver cells.

PMID- 17219954
TI  - A RGD-containing oligopeptide (K)16GRGDSPC: a novel vector for integrin-mediated
      targeted gene delivery.
AB  - A 23 amino acid, bifunctional integrin-targeted synthetic oligopeptide was
      evaluated for ex vivo gene delivery to rabbit bone marrow stromal cells (BMSCs).
      Synthesis of the peptide (K)16GRGDSPC was performed on a solid-phase batch
      peptide synthesizer. BMSCs were transfected with plasmid DNA coding for
      luciferase by (K)16GRGDSPC and the transfection efficiency was assayed. The
      influences of chloroquine and polyethyleneimine on the transfection efficiency
      were also examined. The target specificity of (K)16GRGDSPC to mediate exogenous
      gene into BMSCs was analyzed using cell attachment test and gene delivery
      inhibition test. The results showed that the transfection efficiency of the
      oligopeptide vector was lower than that of Lipofectamine. But in the presence of
      endosomal buffer chloroquine or endosomal disrupting agent polyethyleneimine, the
      transfection efficiency of the vector was greatly enhanced. In addition, RGD
      containing peptides inhibited BMSCs' attachment to the 96-well plates pretreated
      with fibronectin or vitronectin and significantly decreased the transfection
      efficiency of the oligopeptide vector. These studies demonstrated that
      oligopeptide (K)16GRGDSPC was an ideal novel targeted non-viral gene delivery
      vector, which was easy to be synthesized, high efficient and low cytotoxicity.
      The vector could effectively deliver exogenous gene into rat BMSCs.

PMID- 17219955
TI  - Transcription activity of ectogenic human carcinoembryonic antigen promoter in
      lung adenocarcinoma cells A549.
AB  - The transcription activity of ectogenic human carcinoembryonic antigen (CEA)
      promoter in lung adenocarcinoma cells A549 was investigated for the further gene
      targeting therapy. The reporter gene green fluorescent protein (GFP) driven by
      CEA promoter and human cytomegalovirus (CMV) promoter were relatively constructed
      and named plasmid pCEA-EGFP and pCMV-GFP respectively. The intensity of
      fluorescence was detected by fluorescence microscope and flow cytometry analysis
      after the pCEA-GFP and pSNAV-GFP plasmids were transfected into A549 cells
      through liposome respectively. The results showed (4.08+/-0.63) % of the A549
      cells transfected with pCEA-AFP plasmid expressed, significantly lower than that
      of the A549 cells transfected with pCMV-GFP [(43.27+/-3.54) %]. It was suggested
      that ectogenic human CEA promoter in lung adenocarcinoma cells A549 was weakly
      expressed. The distinct specificity of CEA promoter in CEA high expression cells
      was regarded as a tool in selective gene therapy, but the transcription activity
      of ectogenic human CEA promoter was needed to increase in the future.

PMID- 17219956
TI  - Hypoxia-inducible factor-1alpha suppressing apoptosis and increasing tolerance of
      lung cancer cells to chemotherapy.
AB  - In order to construct plasmid of hypoxia-inducible factor-1alpha (HIF-1alpha),
      and transfect into human lung cancer cells A549, the change in sensitivity of
      lung cancer cells A549 to chemotherapy was observed. HIF-1alpha mRNA structure
      region was amplified by RT-PCR and inserted into plasmid pcDNA3. The expression
      plasmid pcDNA3/HIF-1alpha was transfected into A549 with Lipofec-tAMINE2000. The
      expression of HIF-1alpha protein was detected by Western blot. After A549 cells
      were transfected with HIF-1alpha prior to addition of 5-Fu, the growth activity
      was measured by growth curve, apoptosis was detected by flow cytometry at 48 h,
      and the levels of caspase3 and MDR-1 were determined by Western blot. The results
      showed that the constructed expression plasmid was analyzed with restriction
      enzymes and gel electrophoresis. Two DNA lanes at 2.55 kb and 5.4 kb respectively
      were found, which were consistent with that expected. The growth rate in 5-Fu
      group was significantly inhibited, and the apoptosis index and caspase3 activity
      were increased significantly as compared with control group. After HIF-1alpha
      being transfected into A549, the activity of MDR-1 was increased and the effect
      of 5-Fu was weakened. In conclusion, HIF-1alpha can promote chemoresistance by
      increasing the activation of MDRI and suppressing apoptosis during lung cancer
      cells A549 induced with 5-Fu.

PMID- 17219958
TI  - ANP T2238C, C-664G gene polymorphism and coronary heart disease in Chinese
      population.
AB  - The association between atrial natriuretic peptide (ANP) polymorphism and
      coronary heart disease (CHD) was studied in Chinese population. The genotypes of
      ANP T2238C and ANP C-664G were detected by polymerase chain reaction and
      restriction fragment length polymorphism (PCR-RFLP) methods in 158 consecutive
      CHD patients and 165 controls. It was found that the distribution of A2A2
      genotype in CHD group was significantly higher than that in control group
      (P<0.05). Stepwise Logistic regression analysis revealed that male, smoking,
      history of hypertension, history of diabetes, family history of hypertension,
      high level of serum cholesterol, and ANP T2238C polymorphism were the possible
      risk factors in patients with CHD (P<0.05). However, there was no significant
      difference between the patients with CHD and the control group in the
      distribution of ANP C-664G polymorphism (P>0.05). The results suggest that A2A2
      T2238C genotype could be one of the risk factors for CHD (P<0.05, OR: 1.80, 95 %
      CI: 1.03-3.15).

PMID- 17219957
TI  - Influence of L-arginine on the expression of eNOS and COX2 in experimental
      pulmonary thromboembolism.
AB  - The influence of L-arginine on endothelial nitric oxide synthase (eNOS) and
      cyclooxygenase 2 (COX2) was observed in experimental pulmonary thromboembolism
      and the action mechanism on pulmonary thromboembolism was explored. Wistar rats
      were randomly divided into control group, model group and treatment group.
      Pulmonary thromboembolism models were established by auto-blood back transfusion,
      and L-Arg 100 mg/kg was intraperitoneally injected after successful model
      preparation. The animals were sacrificed at 3 h, 1 day, 3 days and 7 days after
      embolism. Plasma NO, TXB2 and 6-Keto-PGFla were detected. The expression of eNOS
      and COX2 protein and mRNA in pulmonary tissues was detected by
      immunohistochemistry and RT-PCR respectively. The results showed that pulmonary
      thrombosis could be seen post pulmonary embolism and inflammatory reaction was
      significant. Plasma NO was decreased (P<0.01), and the levels of TXB2, 6-Keto
      PGF1alpha and T/P ratio were all elevated. The expression of eNOS protein and
      mRNA in the pulmonary tissue was down-regulated (P<0.05), while that of COX2
      protein and mRNA was upregulated (P<0.01). In treatment group, the level of NO
      was increased, the levels of TXB2 and T/P ratio were decreased, but the level of
      6-Keto-PGF1alpha was increased. The expression of eNOS protein and mRNA in
      pulmonary tissue was upregulated (P<0.05), while that of COX2 protein and mRNA
      was down-regulated (P<0.05). In conclusion, L-arginine can educe the role of
      pulmonary tissue protection through up-regulating the expression of intra
      pulmonary NOS and down -regulating COX2 in pulmonary thromboembolism.

PMID- 17219959
TI  - Effects of trichostatin A on HDAC8 expression, proliferation and cell cycle of
      Molt-4 cells.
AB  - The effects of Trichostatin A (TSA) on histone deacetylase 8 (HDAC8) expression,
      proliferation and cell cycle arrest in T-lymphoblastic leukemia cell line Molt-4
      cells in vitro were investigated. The effect of TSA on the growth of Molt-4 cells
      was studied by MTT assay. Flow cytometry was used to examine the cell cycle. The
      expression of HDAC8 was detected by using immunocytochemistry and Western blot.
      The results showed that proliferation of Molt-4 cells was inhibited in TSA
      treated group in a time- and dose-dependent manner. The IC50 of TSA exposures for
      24 h and 36 h were 254.3236 and 199.257 microg/L respectively. The cell cycle
      analysis revealed that Molt-4 was mostly in G0/G1 phase, and after treatment with
      TSA from 50 to 400 microg/L for 24 h, the percents of G0/G1 cells were decreased
      and cells were arrested in G2/M phase. Treatment of TSA for 24 h could
      significantly inhibit the expression of HDAC8 protein in Molt-4 cells (P<0.01).
      It was concluded that TSA could decrease the expression of HDAC8 in Molt-4 cells,
      which contributed to the inhibition of proliferation and induction of cell cycle
      arrest in Molt-4 cells.

PMID- 17219960
TI  - Trichostatin A regulates hGCN5 expression and cell cycle on Daudi cells in vitro.
AB  - The expression of human general control of amino acid synthesis protein 5 (hGCN5)
      in human Burkitt's lymphoma Daudi cells in vitro, effects of Trichostatin A (TSA)
      on cell proliferation and apoptosis and the molecular mechanism of TSA inhibiting
      proliferation of Daudi cells were investigated. The effects of TSA on the growth
      of Daudi cells were studied by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H
      tetrazolium (MTT) assay. The effect of TSA on the cell cycle of Daudi cells was
      assayed by a propidium iodide method. Immunochemistry and Western blot were used
      to detect the expression of hGCN5. The proliferation of Daudi cells was decreased
      in TSA-treated group with a 24 h IC50 value of 415.3979 microg/L. TSA induced
      apoptosis of Daudi cells in a time- and dose-dependent manner. Treatment with TSA
      (200 and 400 microg/L) for 24 h, the apoptosis rates of Daudi cells were (14.74+/
      2.04) % and (17.63+/-1.25) %, respectively. The cell cycle was arrested in G0/G1
      phase (50, 100 microg/L) and in G2/M phase (200 microg/L) by treatment with TSA
      for 24 h. The expression of hGCN5 protein in Daudi cells was increased in 24 h
      TSA-treated group by immunochemistry and Western blot (P<0.05). It was suggested
      that TSA as HDACIs could increase the expression of hGCN5 in Daudi cells, and
      might play an important role in regulating the proliferation and apoptosis of B
      NHL cell line Daudi cells.

PMID- 17219961
TI  - Anticancer activities of trichostatin A on maligant lymphoid cells.
AB  - The anticancer activity of trichostain A (TSA) on human B cell non-Hodgkin's
      lymphoma and its mechanism were explored. The effect of TSA on the growth of Raji
      cells and normal peripheral blood mononuclear cells (NPBMNC) was studied by MTT
      assay. The effect of TSA on the apoptosis of Raji cells and NPBMNC was studied by
      flow cytometry and TDT-mediated dUTP nick end labeling (TUNEL). The effect of TSA
      on the cell cycle of Raji cells was studied by propidium iodide method. The
      results showed that TSA potently inhibited proliferation of Raji cells at
      microgram concentrations and induced apoptosis of Raji cells in a time- and
      concentration-dependent manner. Treatment with TSA induced accumulation of cells
      in G0/G1 or G2/M and a concomitant decrease of cell population in S phase.
      However, NPBMNC was less sensitive to the cytotoxic effect of TSA than Raji
      cells. It was concluded that TSA may inhibit the proliferation of Raji cells by
      regulating the cell cycle and inducing the cell apoptosis. Moreover, TSA
      demonstrates low toxicity in NPBMNC but selectively induces apoptosis of Raji
      cells.

PMID- 17219962
TI  - Effect of antisense FosB and CREB on the expression of prodynorphin gene in rats
      with levodopa-induced dyskinesias.
AB  - The effects of antisense FosB and CREB intra-striatum injection on the expression
      of prodynorphin (PDyn) gene in striatal neurons of Levodopa-induced dyskinesias
      (LID) rats with Parkinson disease (PD) were explored. PD model in rats was
      established by 6-OHDA microinjection stereotaxically. The rats were treated with
      chronic intermittent Levodopa celiac injection for 28 days to get the LID rats.
      Antisense FosB and cAMP response element-binding protein (CREB) were injected
      into striatum of all rats respectively. In situ hybridization was used to measure
      the changes in the expression of PDyn mRNA in striatum and behavior changes were
      observed. The results showed after administration of antisense FosB, abnormal
      involuntary movement (AIM) was decreased and the expression of PDyn mRNA in
      striatum was increased in LID rats as compared with sense FosB group (P<0.01,
      respectively). As compared with the control group, the expression of PDyn mRNA in
      striatum was decreased by antisense CREB-treated LID group (P<0.01) and compared
      with sense CREB treated LID group, antisense CREB-treated LID group showed no
      changes in AIM scores and the expressions of PDyn mRNA (both P>0.05). In
      conclusion, FosB protein, which replaced the CREG, could regulate the expression
      of PDyn mRNA and play critical role in the pathogenesis of LID.

PMID- 17219963
TI  - Changes of regulatory T cells in Graves' disease.
AB  - The immune mechanism of Graves' diseases (GD) and the roles of regulator T cells
      were investigated. In 32 patients with GD (GD group) and 20 healthy volunteers
      (control group), flow cytometry was used to detect the proportion of CD4+CD25+
      cells, MACS to isolate CD4+ CD25+ cells, RT-PCR to assay the expression of FOXP3,
      and ELISA to test the level of IL-10, respectively. It was found that there was
      no significant change in the proportion of CD4+CD25+ T cells between GD group and
      control group (P>0.05), while secretion of IL-10 and expression of FOXP3 in GD
      group were lower than control group (P<0.01 and P<0.05, respectively). In
      conclusion, though the proportion of regulatory T cells of peripheral blood
      lymphocytes in the patients with GD, the functions of them were significantly
      weakened, which might be a pathogenic factor in GD.

PMID- 17219964
TI  - CD4+CD25high regulatory cells in peripheral blood of NSCLC patients.
AB  - The proportion and changes of CD4+CD25high regulatory T cells (Trs) in peripheral
      blood of non-small cell lung cancer (NSCLC) patients were analyzed and their
      clinical significance explored. The peripheral blood was collected from 61
      patients with NSCLC and 15 healthy controls. By using monoclonal antibodies, the
      blood samples were evaluated with the flow cytometry for lymphocyte subsets
      (CD3+, CD4+ and CD8+) and CD4+CD25high Tr cells. The results showed that the
      proportion of CD4+CD25high Tr cells in NSCLC group was significantly higher than
      in control group [(4.36 +/-2.07) % vs (2.04+/-1.03) %, P<0.01]. The proportion of
      CD4+CD25 high Tr cells in late stage was higher than that in early stage [stages
      I +II (2.26+/-0.6) %; stage III (3.28+/-1.38) %; stage IV (6.06 +/-4.08) %]
      (P<0.05). Kaplan-Meier survival analysis revealed that the prognosis of the
      patients who had higher proportion of CD4+CD25high Tr cells in peripheral blood
      was worse (P=0.0026). In conclusion, the relative increase in CD4+CD25high Tr
      cells in peripheral blood may be related to immunosuppression and tumor
      progression in patients with NSCLC. This finding suggests that CD4+CD25+high Tr
      cells in peripheral blood of NSCLC may be positive for prognosis analysis. The
      use of depletion of the CD4+CD25high Tr cell therapy to treat NSCLC patients may
      be an effective strategy.

PMID- 17219965
TI  - Expression of survivin, CDK4, Ki-67 and clinical significance in pediatric acute
      leukemia.
AB  - The expression of Survivin, CDK4 and Ki-67 and the clinical significance in
      pediatric acute leukemia (AL) were investigated. The expression of Survivin, CDK4
      and Ki-67 proteins was detected by using immunohistochemical assay in 37 children
      with AL and 10 children with normal bone marrow as controls. The positive
      expression rate of Survivin, CDK4 and Ki-67 was 45.9 %, 56.8 %, and 40.5 %
      respectively in 37 AL children, which was significantly higher than in control
      group accordingly (P<0.05). The expression of Survivin was positively correlated
      with CDK4 (P=0.007) and Ki-67 (P=0.008). In conclusion, all Survivin, CDK4 and Ki
      67 proteins are over-expressed in pediatric AL and involved in the modulation of
      apoptosis and proliferation in pediatric AL.

PMID- 17219966
TI  - Direct infection of colony forming unit-megakaryocyte by human cytomegalovirus
      contributes the pathogenesis of idiopathic thrombocytopenic purpura.
AB  - Human cytomegalovirus (HCMV) late mRNA expression in megakaryoblast and in turn
      the pathogenesis of idiopathic thrombocytopenic purpura (ITP) patients with HCMV
      infection, and effectiveness of ganciclovir were investigated. Colony forming
      unit-megakaryocytes (CFU-MK) of 46 ITP patients with HCMV infection were
      incubated from patients' bone marrow mononuclear cells (MNC). Reverse
      transcriptase-polymerase chain reaction (RT-PCR) was subsequently used for CFU-MK
      for HCMV-late mRNA detection. Ganciclovir therapy was given to both HCMV-late
      mRNA positive and negative groups for comparison of therapeutic effectiveness.
      The results in 19 of 46 CFU-MK culture cells specimens with positive HCMV-DNA by
      PCR or positive CMV-IgM by enzyme linked immunosorbent assay (ELISA) in the
      correspondent serum of peripheral blood were positive for HCMV-late mRNA. Sixteen
      out of 19, patients with positive HCMV-late mRNA CFU-MK had a positive response
      to ganciclovir. Amongst 27 patients with negative HCMV-late mRNA CFU-MK, only 4
      positive responders to ganciclovir therapy were observed. Curative effectiveness
      of ganciclovir in HCMV-late mRNA positive group was significantly higher than
      that in HCMV-late mRNA negative group (P<0.01). It was suggested that HCMV could
      directly infect CFU-MK, which might be one of the mechanisms responsible for HCMV
      related ITP. The ganciclovir is an effective therapy in resulting in the
      increases in thrombocyte in the ITP patients whose HCMV- late mRNA was positive
      in their CFU-MK.

PMID- 17219967
TI  - Efficacy of subcutaneous administration of gonadotropin-releasing hormone agonist
      on idiopathic central precocious puberty.
AB  - In order to assess the feasibility of subcutaneous administration of Triptorelin
      with 6-week intervals for the suppression of pituitary-gonadal axis and changes
      of clinical signs in girls with idiopathic central precocious puberty (ICPP), 46
      girls with ICPP were treated with GnRHa. Triptorelin (Decapeptyl, 3.75 mg) was
      administered subcutaneously (SC) at 6-weeks intervals or intramuscularly (IM) at
      4-weeks intervals randomly for more than 12 months consecutively. During GnRHa
      therapy, clinical parameters and laboratory data, including height, weight,
      pubertal stage, bone age, uterine volume and ovarian size, serum levels of
      luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2),
      were monitored and analyzed. It was found that both treatment regimes led to
      regression of precocious puberty and reversal of secondary sexual
      characteristics. Breast developments regressed. Uterine volume was decreased
      after treatment, but there was no statistically significant difference. Mean
      ovarian volume did not change significantly during treatment. The height velocity
      was decreased significantly from 6.3+/-1.4 cm/year to 5.8+/-1.2 cm/year in group
      SC and 6.7+/-1.3 cm/year to 5.4+/-1.0 cm/year in group IM, respectively. The rate
      of bone maturation was reduced significantly during treatment. The ratio of
      deltaBA/deltaCA was 1.2+/-0.2 or 1.3+/-0.3 at the onset of therapy and decreased
      significantly after the treatment to 0.7+/-0.2 or 0.9+/-0.1, respectively. The
      predicted adult height was increased significantly and progressively during
      therapy. The levels of serum LH, FSH and E2 returned to the prepubertal
      condition. No significant side effects of therapy were noted. The most common
      side effect during SC treatment was that a non-irritating, 1 cm in diameter mass
      was palpated at the site of subcutaneous injection in the abdominal wall of
      patients, which disappeared after 6-12 weeks. Two girls had minimal withdrawal
      vaginal bleeding episodes after the first injection. It was concluded that both
      IM and SC triptorelin administrations were clinically effective. They induce
      profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing
      height velocity, slowing bone maturation and increasing predicted adult height.
      These results suggest that subcutaneous injection of triptorelin in 6-weeks
      intervals at a dosage of 3.75 mg be a safe and acceptable regimen for ICPP

PMID- 17219968
TI  - Effect of HIF-1alpha on VEGF-C induced lymphangiogenesis and lymph nodes
      metastases of pancreatic cancer.
AB  - The effect of hypoxia inducible factor-1alpha (HIF-1alpha) on vascular
      endothelial growth factor C (VEGF-C) and the correlation between HIF-1alpha and
      lymphangiogenesis and lymph nodes metastases (LNM) in pancreatic cancer were
      investigated. Immunohistochemical SP method was used to detect the protein
      expression of HIF-1alpha and VEGF-C, and Lymphatic vessel density (LVD) was
      determined by stain of VEGFR-3, collagen type IV in 75 pancreatic head cancers
      from regional pancreatectomy (RP) during Dec. 2001 to Dec. 2003. The relationship
      between HIF-1alpha and VEGF-C, lymphangiogenesis, LNM was analyzed statistically.
      The results showed that the positive expressionrate of HIF-1alpha and VEGF-C in
      pancreatic cancer tissues was 48.00 % (36/75) and 65.33 % (49/75) respectively.
      In positive group of HIF-1alpha, the positive rate of VEGF-C and LVD, and LVD
      rate was 80.56 % (29/36), 13.22+/-3.76 and 88.89 % (32/36) respectively, and in
      negative group of HIF-1alpha, positive rate of VEGF-C and LVD was 51.28 %
      (20/39), 5.98+/-2.17 and 66.67 % (26/39) respectively (P<0.01 or P<0.05). It was
      suggested that HIF-1alpha could promote the expression of VEGF-C,
      lymphangiogenesis and LNM in pancreatic cancer.

PMID- 17219969
TI  - Cyclin E expression and chemotherapeutic sensitivity in breast cancer cells.
AB  - The effects of the cyclin E expression levels on chemotherapeutic sensitivity of
      breast cancer cell line were explored. After the cyclin E expression was
      knockdown in MDA-MB-435 by RNA interference, FACS analysis and SA-beta-gal
      staining were used to evaluate the response sensitivity of breast cancer cells to
      DNA damage drugs (adriamycin, etc.). Adriamycin could induce G1 arrest in cyclin
      E knockdown MDA-MB-435 breast cell line and increase the percentage of cell
      senescence in cyclin E knockdown MDA-MB-435 cells. It was suggested that cyclin E
      knockdown could increase the chemotherapeutic sensitivity of breast cancer cells
      to DNA damage drugs.

PMID- 17219970
TI  - Proliferation and differentiation of duct epithelial cells after partial
      pancreatectomy in rats.
AB  - The proliferation and differentiation of pancreatic duct epithelial cells in
      remnant pancreas during regeneration after partial pancreatectomy in rats were
      studied, and the source of pancreatic stem cells was characterized. Partial (90
      %) pancreatectomy was performed on 4- to 5-week-old Sprague-Dawley rats, and
      different duct epithelial cells and acinar cells were detected by
      immunohistrochemical stain method and scored using 5-bromo-2'-deoxyuridine (BrdU)
      labeling index (LI) at various time points after partial pancreatectomy. It was
      found that at 24 h after partial pancreatectomy proliferation started in the
      main, large and small duct cells, and persisted in small duct cells to day 5.
      There was significant difference between the experimental group and the control
      group (P<0.001). Acinar cells positive for BrdU were greatly increased and
      reached the peak LI on day 5. The destroyed lobular architecture almost totally
      recovered on day 7, and the newly islet cells appeared around the pancreatic
      ducts. These results suggest that regeneration after partial pancreatectomy is
      involved in proliferation and differentiation of pancreatic stem cells, and
      pancreatic stem cells may locate in the pancreatic ductules.

PMID- 17219971
TI  - Expression and significance of toll-like receptor 2,4 of peripheral blood
      mononuclear cells in acute abdomen patients associated with systemic inflammatory
      response syndrome.
AB  - The changes of Toll-like receptor (TLR) 2, 4 of peripheral blood mononuclear
      cells (PBMCs) in the acute abdomen patients associated with systemic inflammatory
      response syndrome (SIRS) and their potential significance were explored. A
      clinical study was performed on 103 acute abdomen patients in whom 65 were
      associated with SIRS. Forty healthy individuals served as normal controls. The
      mRNA expression of TLR2, 4 was detected by RT-PCR, and the expression of TNF
      alpha and IL-6 by ELISA. The level of plasma endotoxin, hospital stay and
      mortality were measured. It was found that the endotoxin level was increased to
      varying degrees in all the acute abdomen patients, and the endotoxin level was
      and hospital stay longer in SIRS group than in non-SIRS group (P<0.01). TLR2
      mRNA, TLR4 mRNA, IL-6 and TNF-alpha could be detected with low value in normal
      controls, but they were up-regulated markedly on the 1st day after admission.
      Then TLR4 mRNA, IL-6 and TNF-alpha were decreased gradually, but TLR2 mRNA
      maintained at a high level till the 5th day. These indexes above in SIRS group
      were higher than those in non-SIRS group (P<0.01). The results of correlation
      analysis revealed the expression of TLR2, 4 mRNA was positively correlated with
      the levels of TNF-alpha and IL-6, and the hospital stay. The results of Logistic
      regression demonstrated that overexpression of TLR2, 4 mRNA might result in
      higher risk of multiple organ dysfunction syndrome (MODS). It was concluded that
      in the acute abdomen patients associated with SIRS, the expression of TLR2, 4 in
      PBMCs was increased markedly, suggesting that TLR might play an important role in
      the pathogenesis of acute abdomen associated with SIRS.

PMID- 17219972
TI  - Association between up-regulation of Fas ligand expression and apoptosis of tumor
      infiltrating lymphocytes in human breast cancer.
AB  - In order to study the significance of FasL expression in immune escape of breast
      cancer, FasL protein expression and the number of tumor-infiltrating lymphocytes
      (TILs) in 40 specimens of breast cancer were detected by immunohistochemitry. The
      expression of FasL mRNA was measured by in situ hybridization in the consecutive
      tissue slices of 40 breast cancers respectively. By using terminal
      deoxynucleotidyl transferase-mediaed dUTP nick end labeling (TUNEL), apoptotic
      cells were detected in 40 specimens of breast cancer. The expression of FasL was
      detected in all 40 specimens to varying degrees. In the consecutive tissue
      slices, the location of expression of FasL protein corresponded with that of FasL
      mRNA. In those with FasL extensive expression, the number of TILs was less
      (P<0.05), the apoptotic index (AI) of TILs was higher and the AI of tumor cells
      was lower (P<0.01) than those with FasL weak expression respectively. The AI of
      TILs was correlated with that of tumor cells (r= -0.629, P<0.01). In conclusion,
      breast cancer cells can induce the apoptosis of TILs through the expression of
      FasL, which can counterattack the immune system. This may be a mechanism of
      immune evasion in breast cancer.

PMID- 17219973
TI  - A novel frequent BRCA1 allele in Chinese patients with breast cancer.
AB  - The whole length of exon 11 of BRCA1 was sequenced (total 3427 bp) in 59 patients
      and 10 healthy female blood donors. To allow a rapid determination of the
      different BRCA1 alleles, a sequence-specific primer PCR method (PCR-SSP) was
      established and was applied to 57 additional female donors. Finally, the full
      length coding region of BRCA1 was analyzed through reversed-transcriptase PCR (RT
      PCR) and cDNA sequencing (total 5554 bp) in one donor with wild-type allele and 2
      patients with one or two mutated alleles. By genomic DNA sequencing, 5 homozygous
      polymorphisms were observed in 18 patients: 2201C>T, 2430T>C, 2731C>T, 3232A>G
      and 3667A>G All of them were previously observed in Caucasians, Malay and
      Chinese, but for the first time the mutations were found in one allele (GenBank
      AY304547). Twenty-six patients and 4 donors were heterozygous at these 5
      nucleotide positions. The remaining 15 patients and 6 donors showed a sequence
      identical with the standard BRCA1 gene. Combined the PCR-SSP results and in a
      summary, 6 of 67 (9.0 %) healthy individuals were homozygous for the mutated
      allele, whereas 18 of 59 (30.5 %) breast cancer patients were homozygous. A Chi
      square test showed a significant correlation between homozygous mutated BRCA1
      allele and breast cancer. The cDNA sequencing showed that 2 additional mutations,
      4427T>C in exon 13 and 4956A>G in exon 16, were found. A new BRCA1 allele, which
      is BRCAI-2201T/2430C/2731T/3232G/3667G/4427C/4956G (GenBank AY751490), was found
      in Chinese. And the homozygote of this mutated allele may implicate a disease
      association in Chinese.

PMID- 17219974
TI  - The role of sICAM-1 detection in the diagnosis of acute rejection following liver
      transplantation.
AB  - In order to evaluate the applied value of soluble intracellular adhesion molecule
      1 (sICAM-1) in acute rejection (AR) following liver transplantation, the
      expression of sICAM-1 protein was sequentially detected by using ELISA in serum
      and bile of 43 patients receiving liver transplantation. In AR group, the
      expression levels of sICAM-1 protein were increased 3 days before and immediately
      on the establishment of AR diagnosis, and there was significant difference in the
      expression of bile between AR group and control group (P<0.01). After reversion
      of AR with hormone intensive therapy, there was significant difference in the
      sICAM-1 protein expression of serum and bile between AR group and control group.
      It was concluded that the sequential detection of sICAM-1 protein level in serum
      and bile was a reliable and noninvasive method for the early diagnosis of AR
      after liver transplantation and was valuable to observe the curative effects of
      anti-AR therapy.

PMID- 17219975
TI  - Expression of cytokines in acute heart transplantation rejection.
AB  - The expression and changes of local cytokines network were detected in heart
      transplantation in rats, so as to determine the role of cytokines in the acute
      rejection of rats of heart transplantation. Allografts were divided into 4 groups
      (n=12 in each group): group A (control), group B (IL-2 monoclonal antibody
      treated), group C (CsA-treated) and group D (IL-2 monoclonal antibody+CsA
      treated). Hearts from DA rats were transplanted into a cervical location in
      Wistar recipients. The local expression of IL-1beta, IL-2, CD25, IL-4, IL-5, IL
      6, 1L-10, TNFalpha and INFgamma was detected at day 1, 3, 5, 7, 9, 11 and 14 by
      reverse transcription polymerase chain reaction. The results showed that the
      survival time of allografts was 8.3+/-1.7, 29.2+/-7.1 (P<0.05), 26.4+/-5.7
      (P<0.05) and 55.0+/-10.6 (P<0.01) days respectively in groups A, B, C and D. The
      expression of IL-1beta, IL-4, IL-10 and IFNgamma was up-regulated, and that of IL
      2, CD25, IL-5, IL-6 and TNFalpha was significantly inhibited in group A; The
      expression of IL-10, IL-5, IL-6, IL-10 and IFNgamma was up-regulated, and that of
      IL-2, L-4 and TNFalpha was significantly down-regulated in group B; The
      expression of IL-1beta, IL-2, CD25, IL-5, TNFalpha and IFNgamma was up-regulated,
      and that of IL-4, IL-6 and IL-10 was significantly down-regulated in group C; The
      expression of IL-14, 11-5, IL-6 and 11-10 was up-regulated, and that of IL-10, IL
      2, CD25, TNFalpha and IFNgamma was significantly down-regulated in group D. In
      conclusion, cytokines play an important role in the development of acute
      transplantation rejection. Different cytokines play different roles in different
      local environments.

PMID- 17219976
TI  - Clinical significance of VEGF-C and VEGFR-3 expression in non-small cell lung
      cancer.
AB  - The relationship between vascular endothelial growth factor-C (VEGF-C)/vascular
      endothelial growth factor receptor 3 (VEGFR-3) expression and clinicopathologic
      features of the patients with non-small cell lung cancer (NSCLC) was
      investigated. The expression of VEGF-C and VEGFR-3 was assessed in 65 patients
      with NSCLC by immunohistochemistry. The significance of VEGF-C and VEGFR-3
      expression was analyzed statistically. The results showed that VEGF-C and VEGFR-3
      were highly expressed in cytoplasm and membrane in lung cancer tissues with the
      positive rate being 55.4 % and 52.3 % respectively, while there was no expression
      in the normal lung tissues. The expression of VEGF-C was significantly increased
      in adenocacinoma as compared to other types of NSCLC (P<0.05). The VEGFR-3
      expression was closely related with lymph node metastasis (P<0.01) and TNM stage
      (P<0.05). There was a positive correlation between the VEGF-C and VEGFR-3
      expression in NSCLC patients (r=0.658, P<0.01). It is suggested that VEGFR-3
      plays an important role in the lymphatic metastasis of NSCLC. The interaction
      between VEGF-C and VEGFR-3 may be deeply involved in the mechanism of lung cancer
      metastasis.

PMID- 17219977
TI  - Inhibitory effect of pulmonary carcinoma by adenovirus-mediated CD/UPRT gene.
AB  - The cell killing effects and bystander effects of double suicide gene on
      pulmonary carcinoma cells were explored. Lung adenocarcinoma cells (A549) were
      transfected with different titers of adenovirus vector and followed with
      different concentrations of 5-FC after a recombinant adenovirus vector carrying
      CD/UPRT gene (Ad-CD/UPRT) was constructed. The cell viability was measured by MTT
      assay 4 days later. The cell viability was dropped to 30.57 %-8.62 % after 10 MOI
      of Ad-CD/UPRT transfected and 5-FC (10-1000 microg/mL) administration.
      Furthermore, Ad-CD/UPRT-infected A549 cells showed a profound neighbor cell
      killing effect in the same methods. These results suggested that Ad-CD/UPRT/5-FC
      system can effectively suppress growth of lung adenocarcinoma cells, which may
      provide a novel and powerful candidate for lung cancer gene therapy strategies.

PMID- 17219978
TI  - Self-assembled IKVAV peptide nanofibers promote adherence of PC12 cells.
AB  - Lack of biocompatibility and bioactivity is a big problem for the synthetic
      materials that have been generated for neural tissue engineering. To get around
      the problem and generate better scaffold for neural tissue repair, we intended to
      generate nano-fibers by self-assembly of polypeptide IKVAV. Bioactive IKVAV
      Peptide-Amphiphile (IKVAV-PA) was first synthesized and purified, the property of
      which was analyzed and determined by high-performance liquid chromatography
      (HPLC) and mass spectrometry (MS). Then, by addition of hydrogen chloride (HCl),
      self-assembly of IK-VAV-PA was induced in vitro and nano-fibers formed as shown
      by transmission electron microscopy (TEM). The effect of IKVAV nanofibers on
      adherence of PC12 cells was assayed in cell culture and the results showed that
      the rates of adherence of PC12 increased significantly when the density of IKVAV
      was within a certain range (0.58 microg/cm2 to 15.6 microg/cm2). However, its
      effect on the rates of adherence did not significantly alter with time, whether
      after 1 hour or 3 hours of culture. In general, we showed that IKVAV-PA can
      successfully self-assemble to form nanofiber, and promote rapid and stable
      adherence of PC12 cells, and the effect of the self-assembled IKVAV to promote
      PC12 cells adherence is dosage-dependent within a certain range of densities.

PMID- 17219979
TI  - Experimental study on low intensity ultrasound and tissue engineering to repair
      segmental bone defects.
AB  - In order to evaluate the efficacy of low intensity ultrasound and tissue
      engineering technique to repair segmental bone defects, the rabbit models of 1.5
      cm long rabbit radial segmental osteoperiosteum defects were established and
      randomly divided into 2 groups. All defects were implanted with the composite of
      calcium phosphate cement and bone mesenchymal stem cells, and additionally those
      in experimental group were subjected to low intensity ultrasound exposure, while
      those in control group to sham exposure. The animals were killed on the
      postoperative week 4, 8 and 12 respectively, and specimens were harvested. By
      using radiography and the methods of biomechanics, histomorphology and bone
      density detection, new bone formation and material degradation were observed. The
      results showed that with the prolongation of time after operation, serum alkaline
      phosphatase (AKP) levels in both groups were gradually increased, especially in
      experimental group, reached the peak at 6th week (experimental group: 1.26
      mmol/L; control group: 0.58 mmol/L), suggesting the new bone formation in both
      two group, but the amount of new bone formation was greater and bone repairing
      capacity stronger in experimental group than in control group. On the 4th week in
      experimental group, chondrocytes differentiated into woven bone, and on the 12th
      week, remodeling of new lamellar bone and absorption of the composite material
      were observed. The mechanical strength of composite material and new born density
      in experimental group were significantly higher than in control group, indicating
      that low intensity ultrasound could not only effectively increase the formation
      of new bone, but also accelerate the calcification of new bone. It was concluded
      that low intensity ultrasound could evidently accelerate the healing of bone
      defects repaired by bone tissue engineering.

PMID- 17219980
TI  - Inhibition of cell growth and telomerase activity in osteosarcoma cells by DN
      hTERT.
AB  - In order to study the effects of dominant negative human telomerase reverse
      transcriptase (DN-hTERT) on cell growth and telomerase activity in osteosarcoma
      cell line MG63, MG63 cells were transfected with DN-hTERT-IRES2-EGFP9 (DN) or
      IRES2-EGF (I, blank vector) with lipofectamine 2000. The stably transfected cells
      were selected with G-418. Cell growth properties were examined under a
      fluorescence microscope. The hTERT mRNA expression was detected by reverse
      transcription-polymerase chain reaction (RT-PCR). Telomerase activities were
      measured by TRAP-ELISE. The tumorigenicity was studied with tumor xenografts by
      subcutaneous injection of cancer cells into nude mice. The results showed that
      cell growth was suppressed in MG63 cells transfected with DN-hTERT. The hTERT
      mRNA was increased in N-hTERT transfected-MG63 cells (MG63/DN). The telomerase
      activity was 2.45-0.11 in MG63/DN cells, while 3.40+/-0.12 in the cells
      transfected with blank vector (MG63/I), (P<0.05); DN-hTERT-expressing clones did
      not form tumors in 2 weeks, but the ratio of tumorigenesis was 30 % in nude mice
      bearing MG63/I (P<0.01). It was concluded that DN-hTERT could specifically
      inhibit the cell growth and telomerase activity in MG63 cells.

PMID- 17219981
TI  - Effect and mechanism of epidermal growth factor on proliferation of GL15 gliomas
      cell line.
AB  - The effects of epidermal growth factor (EGF) on proliferation of G15 glioma cells
      and the possible mechanisms were investigated. GFAP and EGFR expression was
      detected by immunohistochemical method. After the cells were treated with EGF at
      different concentrations, cell count method was used to determine the
      proliferation of glioma cells, cell cycle and apoptosis were analyzed by flow
      cytometry (FCM), and laser scan confocal microscope (LSCM) was used to measure
      the cytoplasmic free calcium. The results showed that GFAP was diffusedly
      expressed in GL15 cells and EGFR was over-expressed. EGF at doses of < or =1
      ng/mL could significantly stimulate cell proliferation, cells in phase G0/G1
      decreased, and those in phase S increased. EGF at doses of 10 and 100 ng/ml could
      inhibit the cell proliferation significantly, and the apoptosis ratio in high
      dose of EGF group was higher than in control group. EGF could significantly
      induce a quick rise of intracellular free calcium, but the peak value of
      intracellular free calcium activated by high dose of EGF was higher than by low
      dose of EGF. It was suggested that EGF had a dual effect on gliomas: low dose of
      EGF could stimulate the cell proliferation of gliomas, but high dose of EGF could
      induce the cell apoptosis and inhibit the proliferation of gliomas, which might
      be contributed to the difference of intracellular free calcium.

PMID- 17219982
TI  - Pharmacological investigation of voltage-dependent Ca2+ channels in human
      ejaculatory sperm in vitro.
AB  - The types of the voltage-dependent calcium channels (VDCCs) in human ejaculatory
      sperm and the effects of calcium channel blocker (CCB) on human sperm motility
      parameters in vitro were investigated. The human sperm motility parameters in
      vitro in response to the pharmacological agents nifedipine (NIF, inhibitor of L
      type VDCC) and co-conotoxin (GVIA, inhibitor of N-type VDCC) were compared and
      analyzed statistically. The results showed that NIF (1, 5, 10 micromol/L) could
      not only significantly affect human sperm's shape but also spermatozoa motility
      after incubated at least 10 min in vitro (P<0.001). GVIA (0.1, 0.5 and 1
      micromol/L) could just only significantly affect human sperm's progressive
      motility (a %+b %) after incubated for 20 min in vitro (P<0.01), but they both
      could not significantly affect spermic abnormality rate. It is suggested that L
      type VDCC, non L-type VDCCs and isoform of L-type VDCC exist in the cell membrane
      of human sperm solely or together, and they participate in the spermic
      physiological processes especially the spermic motility.

PMID- 17219983
TI  - Cooperative therapeutic effects of herpes simplex virus thymidine kinase
      gene/ganciclovir system and chemotherapeutic agents on prostate cancer in vitro.
AB  - The killing effects of herpes simplex virus thymidine kinase gene/ganciclovir
      (HSV-tk/GCV) approach by the addition of several commonly clinical
      chemotherapeutic agents on hormone refractory prostate cancer (HRPC) cells PC-3m
      were investigated. After transferring of the HSV-tk gene into PC-3m cells, mRNA
      and protein expression of HSV-tk was detected by reverse-transcript polymerase
      chain reaction (RT-PCR) and strept avidin-biotin complex (SABC)
      immunohistochemical method. The killing effect of GCV, cisplatin (CDDP),
      etoposide (VP-16), vincristine (VCR), methotrexate (MTX), 5-fluorouracil (5-Fu),
      and suramin on PC-3m cells was evaluated by morphological assessment analysis,
      trypan blue exclusion assay and MTT assay respectively. Additionally, the
      cooperative effect of HSV-tk/GCV system combined with the above agents on the
      target cancer cells was determined by MTT. Furthermore, apoptosis and necrosis
      induced by GCV plus 5-Fu or suramin was analyzed by flow cytometry (FCM). The
      results showed that that there was HSV-tk mRNA and protein expression in pDR2-tk
      plasmid transduced PC-3m cell. Combination of GCV with VP-16, VCR, 5-Fu or
      suramin led to an enhanced cellular killing effect, but with CDDP resulted in a
      reduced one and with MTX in an approximate one. FCM revealed that synergistic use
      of GCV and 5-fu or suramin resulted in a rather large proportion of apoptosis and
      necrosis with the apoptosis index being 36.38% and 35.51%, and the proportion of
      necrosis being 33.05% and 28.87%, respectively. In conclusion, HSV-tk/CGV
      approach by addition of certain clinical available chemotherapeutic drugs brings
      on statistically significant enhanced cell killing over single-agent treatment.
      Our results highlight the potential for such new combination therapies for future
      treatments of HRPC.

PMID- 17219984
TI  - Effects of shRNA targeting survivin on apoptosis of human retinoblastoma cell
      line Hxo-rb44 in vitro.
AB  - In order to construct a recombinant plasmid containing short hairpin RNA (shRNA)
      targeting survivin and to investigate its effect on survivin expression and cell
      apoptosis of human retinoblastoma cell line Hxo-rb44 in vitro, RNA interference
      plasmid pSIRENS that can express shRNA of survivin was designed, constructed, and
      transfected into human retinoblastoma cell line Hxo-rb44. Survivin and c-Myc
      expression was detected by reverse transcription polymerase chain reaction (RT
      PCR) and Western blot. Apoptosis of Hxo-rb44 cells was assayed by Honchest33258
      staining and cell growth curve was drawn. The results showed that the
      oligonucleotide targeting survivin was identified in pSIRENS plasmid. After
      pSIRENS plasmid transfected, survivin and c-Myc expression in Hxo-rb44 cells was
      decreased significantly. Apoptotic rate of cells was up-regulated from (3.5+/
      1.29) % to (36.1+/-19.66) %. The proliferation ability of Hxo-rb44 cells was
      inhibited. No significant effects on survivin expression and apoptosis of the
      cells were found when negative control plasmid was transfected. In conclusion,
      the plasmid containing shRNA targeting survivin was constructed successfully. It
      could inhibit efficiently the expression of survivin and c-Myc in human
      retinoblastoma cell Hxo-rb44 in vitro. The inhibition of the expression of c-Myc
      might be involved in the apoptosis of Hxo-rb44 cells.

PMID- 17219985
TI  - Resection and cryotherapy combined with amniotic membrane transplantation for the
      treatment of vernal keratoconjunctivitis with giant papillae.
AB  - To evaluate the efficacy and safety of resection and cryotherapy combined with
      amniotic membrane transplantation (AMT) for the treatment of vernal
      keratoconjunctivitis (VKC) with giant papillae (GP). Eight patients (16 eyes
      involved) with VKC, characterized by GP on the upper tarsal conjunctiva,
      underwent resection and cryotherapy in combination with AMT. The follow-up lasted
      for 3-22 months. The results showed that corneal shield ulcers and superficial
      punctuate keratitis healed during the first week after surgery and did not recur.
      Fourteen eyes (87.5 %) were symptom-free 1 month after surgery, and no GP,
      ectropion, trichiasis and other complications were noted, but the blood vessels
      of upper tarsal conjunctiva could not be clearly seen and a little conjunctival
      scar was observed. Recurrence of GP was observed in 2 eyes (12.5 %), with the
      area being less and irritation milder as compared with those before the
      operation. Among the two eyes, one eye was treated by cyclosporine eyedrops with
      improvement, but the other eye showed no improvement after the treatment, and
      underwent a second surgery with a cotton patch soaked in fluorouracil applied
      onto the supratarsal area after resection and cryotherapy. Four months after the
      treatment the patient presented no symptoms and GP did not recur. It is concluded
      that the resection and cryotherapy combined with AMT is an effective and safe
      treatment for VKC with GP.

PMID- 17219986
TI  - Vascular endothelial growth factor165-regulated nasopharyngeal carcinoma cell
      lines invasion and migration involve expression and activation of matrix
      metalloproteinase-2.
AB  - The effect of vascular endothelial growth factor (VEGF) overexpression on matrix
      metalloproteinase-2 (MMP-2) in nasopharyngeal carcinoma (NPC) cells in vitro and
      the possible mechanism involved were investigated, and the correlation between
      the expression of VEGF and MMP-2 in NPC evaluated. The NPC cells were transfected
      with PAd-trackVEGF165 plasmid. The expression levels of VEGF and MMP-2 mRNA and
      protein in NPC cells were detected by semi-quantitative RT-PCR and Western blot
      respectively. It was found that the expression of VEGF and MMP-2 mRNA and protein
      was significantly increased in NPC cells after transfection of VEGF165. It was
      concluded that the expression of VEGF was correlated to the in vitro invasion of
      NPC cells, and the induction of MMP-2 by VEGF was a key process of NPC cell
      invasion.

PMID- 17219987
TI  - Real-time three-dimensional echocardiography in assessment of congenital double
      orifice mitral valve.
AB  - The application of real-time three-dimensional echocardiography (RT 3DE) in the
      diagnosis of double orifice mitral valve (DOMV) was explored. Five cases of DOMV
      were examined by using 2-dimensional echocardiography (2DE) and RT 3DE. The
      spatial morphology of malformed mitral valve and its change in hemodynamics were
      observed. DOMV associated with partial atrioventricular septal defect was found
      in 3 cases (in which 2 cases had cleft mitral valve) and isolated DOMV in 2
      cases; and moderate to severe mitral regurgitation was detected in 3 cases, and
      mild mitral regurgitation in 1, and no regurgitation in 1 case; 1 case had
      complicated rhumatic heart disease. Three cases were preoperatively discovered by
      2DE, while 2 missed (1 case was discovered postoperatively). Four cases were
      diagnosed by RT 3DE preoperatively, and 1 case was diagnosed postoperatively (not
      examined by RT 3DE preoperatively). It was suggested that RT 3DE is a reliable
      technique in the diagnosis of DOMV; it permitted comprehensive and noninvasive
      assessment of mitral valve and may supplement 2D TTE in the assessment of DOMV.

PMID- 17219988
TI  - Ultrasonographic evaluation of osteosarcomas.
AB  - The ultrasonographic appearances of osteosarcomas and the roles of
      ultrasonography in the diagnosis and surgical staging of osteosarcomas were
      investigated. A comparative study was performed on 45 cases of osteosarcomas by
      ultrasonography and radiography. Bony changes, periosteal reaction and soft
      tissue mass were evaluated for each lesion. The results showed that
      ultrasonography revealed a solid mass around bone in 42 patients, bone
      destruction in 24 patients and periosteal reaction in 16 patients. Plain
      radiographs showed bony changes in 44 patients and no bony change in remaining
      one patient, shadowing of soft tissue swelling in 30 patients, and pulmonary
      metastases in 3 patients. Surgical biopsy and pathological examination confirmed
      osteosarcoma in all 45 patients. Soft tissue mass was confirmed in 42 patients
      surgically. The diagnostic accuracy of soft tissue masses by ultrasonography and
      radiography was 100 % (42/42) and 71.4 % (30/42), respectively. The positive rate
      of ultrasonography and radiography in displaying bony changes was 53.3 % (24/45)
      and 97.8 % (44/45), respectively. In conclusion, in the detection of soft tissue
      mass of osteosarcoma, ultrasonography is superior to radiography, and in
      displaying bony changes of osteosarcomas, radiography is superior to
      ultrasonography. So it may come to a conclusion that plain radiography combined
      with ultrasonography can completely display the bony and soft tissue lesion of
      osteosarcomas.

PMID- 17219989
TI  - Molecular characterization of duck hepatitis B virus isolated from Hubei brown
      ducks.
AB  - The objective of this study was to characterize the genome structure of duck
      hepatitis B virus (DHBV) isolated from Hubei brown ducks. The natural carrier
      rate of DHBV in adult ducks from Hubei area was investigated and the DHBV DNA
      positive serum screened out. The complete genome of a DHBV strain was amplified
      by polymerase chain reaction (PCR) and cloned into T vector and sequenced. The
      results showed that the carrier rate of DHBV in Hubei brown ducks was 10 %. This
      strain (GenBank accession number DQ276978) had a genome of 3024 nucleotides with
      three overlapping open reading frames encoding the surface, core and polymerase
      proteins respectively. Comparison of the strain with 17 DHBV strains registered
      in GenBank revealed a homology from 89.3 % to 93.5 % at the nucleotide level. The
      sequences of the structural and functional domains of these proteins were highly
      conserved. The strain was found to share more signature amino acids in the
      polymerase genes with the "Chinese" DHBV strains than those of the "Western"
      country strains. This finding was also corroborated by a phylogenetic tree
      analysis. Therefore, the DQ276978 might belong to a subtype of the Chinese DHBV
      strains.

PMID- 17219990
TI  - [Expression of telomerase reverse transcriptase and its relationship with
      expression of c-myc in laryngeal squamous cell carcinomas].
AB  - OBJECTIVE: To investigate the expression of human telomerase reverse
      transcriptase (hTERT) and c-myc and their relationship with clinicopathological
      parameter in laryngeal squamous cell carcinoma (LSCC). METHOD: The expression of
      hTERT protein and c-myc protein in 39 LSCC specimens and 10 vocal cord polyp
      specimens were detected by immunohistochemistry. The correlation between the
      expression of hTERT protein and c-myc protein and their relationship with
      clinicopathological parameter were analyzed. RESULT: The positive rate of hTERT
      protein and c-myc protein expression in 39 LSCC was 84.6% (33/39) and 82.1%
      (32/39), respectively. The positive rate of hTERT protein and c-myc protein
      expression in 10 vocal cord polyps was 0 (0/10) and 10.0% (1/10) respectively.
      Statistical tests showed that hTERT and c-myc protein expression was
      significantly higher in LSCC than that in vocal cord polyps. Spearman rank
      correlation analysis revealed that the expression of c-myc protein was great
      significantly related to that of hTERT protein (correlation coefficient r =
      0.541, P < 0.01). No statistically association was observed among the frequency
      of hTERT expression and TNM stages, degree of differentiation or lymph nodes
      metastases. CONCLUSION: The activation of hTERT may be a key step in the
      pathogenesis of LSCC and the expression of hTERT was associated significantly
      with that of c-myc gene. C-myc is probably an important control factor in the
      activation and regulation of hTERT expression.

PMID- 17219991
TI  - [Expression of Survivin and its correlation with tumor angiogenesis in
      differentiated thyroid carcinomas].
AB  - OBJECTIVE: To identify the expression of Survivin and its relationship with tumor
      angiogenesis in differentiated thyroid carcinomas. METHOD: The expression of
      Survivin, VEGF and MVD were detected by immuno-histochemical staining (SP
      methods) in 47 differentiated thyroid carcinomas, 10 thyroid adenoma and 10
      normal thyroid tissues and their content were measured by pathological image
      analysis system. RESULT: The expression of Survivin and VEGF in differentiated
      thyroid carcinomas was 46.8% and 61.7%, respectively. No expression of Survivin
      was detected in thyroid adenoma and normal thyroid tissues. The expression of
      Survivin was significantly correlated with the expression of VEGF and MVD in
      differentiated thyroid carcinomas. The expression of Survivin was significantly
      associated with clinical stages, tumor complete capsule and lymph node
      metastasis. CONCLUSION: The up-regulation of Survivin expression and its close
      relationship with angiogenesis may play an important role in carcinogenesis and
      development of differentiated thyroid carcinomas.

PMID- 17219992
TI  - [Quantitative evaluation of the focus range of juvenile onset recurrent
      respiratory papillomatosis].
AB  - OBJECTIVE: To investigate the clinical application of quantitative evaluation of
      the focus range of juvenile onset recurrent respiratory papillomatosis (JO-RRP).
      METHOD: Disease severity was scored as the sum of ratings of 1 (minimal), 2
      (moderate), or 3 (severe) for involvement of 22 areas of the respiratory tract
      and digestive tract. Sixty-eight cases with JO-RRP patients underwent 238
      procedures were removed papillomas. A Storz laryngoscope was used to exposed and
      suspend the larynx, and an endoscope video system was used to display the
      pathological changes. RESULT: The score of these cases range from 2 to 20, most
      of them range from 7 to 14. Papillomas were found in the larynx in each case,
      vocal cords and false vocal cords were the most common places involved. Nose,
      pharynx, hard palate, lung or esophagus involved was seldom found. The score
      declined as the patients underwent more procedures. It is in accord with the
      clinical characteristic of JO-RRP. CONCLUSION: We concluded that our means of JO
      RRP focus range quantitative evaluation could evaluate the severity and clinical
      curative effect objectively. It was a scientific and convenient way, and worth to
      be generalized.

PMID- 17219993
TI  - [Congenital unilateral malformations of lung referred as bronchial foreign
      bodies].
AB  - OBJECTIVE: To investigate the resemblances and differences of congenital
      unilateral malformations of lung and bronchial foreign bodies in clinical
      manifestation, physical sign and radiological examination, and to summarize the
      characteristics and to introduce diagnostic methods of the congenital unilateral
      malformations of lung. METHOD: Ten patients with the congenital unilateral
      malformation of lung, who were diagnosed the pulmonary atelectasis or the
      bronchial foreign body initially, were analyzed. Three typical cases were
      analyzed in details. RESULT: Four patients were confirmed by rigid bronchoscope.
      Four patients were confirmed by X-ray and high resolution CT of lung, one patient
      by high- resolution CT and 3D stereographs of lung, one patient by autopsy. Six
      cases were the congenital malformations of the right lung and 4 cases were the
      left lung. Three cases of them combined with congenital cardiovascular diseases
      and other malformations. CONCLUSION: There are many resemblances between the
      congenital unilateral malformation of lung and the bronchial foreign body in
      clinical manifestation and physical sign. The congenital unilateral malformation
      of lung was referred as the bronchial foreign body easily. Although it can be
      confirmed by rigid bronchoscope, the risk of the operation for these children was
      very high. So if the disease was considered, high resolution CT and 3D 
      stereographs of lung can make a definite diagnosis.

PMID- 17219994
TI  - [The combined treatment of juvenile outset recurrent respiratory papillomatosis].
AB  - OBJECTIVE: To explore the effective treatment of juvenile outset recurrent
      respiratory papillomatosis (JO-RRP). METHOD: Thirty six patients of JO-RRP from
      1993 to 2004 were analyzed retrospectively. Twenty seven patients were underwent
      laser excision by laryngoscope and nine patients were underwent laser excision
      through laryngostomy. Twenty eight patients who recurrenced more than two times
      in one year or involved extent of disease more than two anatomical subregion were
      give interferon after operation one week in addition. RESULT: All patients had
      normal deglutition, 28 cases (77.8%) had been succeed in decannulation. The
      complications included hoarseness in 8 cases, laryngeal stenosis in 6 cases and
      pulmonary infection in 3 cases. CONCLUSION: The laser surgery by larynoscope and
      laryngostomy are two kinds of effective treatments for JO-RRP. The interferon
      therapy after the operation can restrain the recrudescence effectively.

PMID- 17219995
TI  - [Preservation of laryngeal function in surgical treatment of T3 supraglottic
      laryngeal carcinoma].
AB  - OBJECTIVE: To explore the feasibility,surgical techniques and the clinical
      curative effect of preservation of laryngeal function in surgical treatment of T3
      supraglottic laryngeal carcinoma (SLC). METHOD: A retrospective review of 70
      cases with T3 SLC that we treated from 1994 to 2003 were accomplished. All of the
      cases were treated with partial laryngectomy. Among them, 42 cases underwent
      supraglottic horizontal partial laryngectomy, 19 supraglottic horizontovertical
      laryngectomy, 8 supracricoid partial laryngectomy and 1 near total laryngectomy.
      All patients were received postoperation radiotherapy with the dosage for 50-60
      Gy. RESULT: The 3 year and 5 year-survival rates were 79.2% and 68.4%,
      respectively. Out of the 70 cases, 60 cases were decannulated with a
      decannulation rate of 85.7%. The normal diet was resumed in all patients, no
      buckling and dysphagia obviously. All patients had their successful phonation, no
      one failure for laryngotracheal atresia. CONCLUSION: It is feasibility to
      preservative laryngeal function in surgical treatment of T3 SLC, if surgeons
      master indications correctly, use many kinds restorative procedure expertly and
      improve surgical skill.

PMID- 17219996
TI  - [In situ preservation of parathyroid glands in total or near total
      thyroidectomy].
AB  - OBJECTIVE: To investigate the preservation of parathyroid glands and its function
      during total or near-total thyroidectomy. METHOD: One hundred and thirty one
      patients underwent total thyroidectomy, near total thyroidectomy,
      hemithyroidectomy and isthmectomy. In operation, the parathyroid glands were
      exposed, or were identified under microscope when necessary. The third rank of
      inferior thyroid arteries was ligated to preserve parathyroid glands in situ, and
      the parathyroid function was observed after thyroidectomy. RESULT: Four patients
      (3%) had a transient hypoparathyroidism after thyroidectomy, 26 patients (20%)
      had a obviously biochemical hypocalcemia with no symptoms, 73 patients (56%) had
      a lower calcium level in the first 3 days after surgery compared with
      preoperative level, 28 (21%) patients who underwent ipsilateral total and
      contralateral subtotal isthmectomy were all normocalcemic after surgery. There
      were no permanent hypoparathyroidism and death in our study population.
      CONCLUSION: In total or near-total thyroidectomy, parathyroid glands and its
      artery blood-supply should be exposed and preserved. Vasodilator and calcium
      supplementation should be given to patients with obviously lower serum calcium
      level after surgery to prevent permanent hypoparathyroidism.

PMID- 17219997
TI  - [The value of spiral CT scan to diagnose the respiratory tract foreign body with
      negative chest X-rays].
AB  - OBJECTIVE: To study the value of spiral CT scan in diagnosis of the respiratory
      tract foreign body in children. METHOD: Eighty-four patients with negative chest
      X-rays who were considered to have respiratory tract foreign body were done chest
      spiral CT scans. RESULT: All cases were found foreign body under spiral CT scans.
      CONCLUSION: Spiral CT scan is a special and valuable diagnostic method for
      respiratory tract foreign body. It can make up for the lack of chest X-rays.

PMID- 17219998
TI  - [Suppression of proliferation of Hep-2 cells by stable expression of anti-sense
      perlecan cDNA].
AB  - OBJECTIVE: To study the suppression of proliferation of Hep-2 cells by stable
      expression of anti-sense perlecan cDNA. METHOD: In this study, the plasmids of
      recombination eukaryotic expression vector perlecan anti-sense cDNA (pAP) were
      transfected into Hep-2 cells by using cationic liposome (lipofectamine 2000) and
      divided into three groups: non-transfected group, WT group; transfection with no
      load carrier, neo group; and transfection with the pAP plasmid, pAP group. Semi
      quantify RT-PCR, western blot assay and MTT assay were used to detected the
      expression of perlecan mRNA and protein in the three groups; the level of cell
      proliferation; and the responsivity of basic fibroblast growth factor (bFGF).
      RESULT: It was showed that the expression of perlecan mRNA and protein were
      significantly reduced in the pAP group compared with WT group and ph beta Apr
      neol transfected group ( P < 0.01). In the presence of 1 microg/L of bFGF in low
      serum (0.1% FCS), the pAP transfected cells showed a reduced proliferation rate
      (MTT assay) while the wild type cells and ph beta Apr-neol transfected cells grew
      rapidly. CONCLUSION: The growth of Hep-2 cells could be inhibited significantly
      by perlecan anti-sense cDNA plasmids transfection.

PMID- 17219999
TI  - [Effect of inhibiting aquaporin-1 on proliferation and apoptosis of the Hep-2
      cell].
AB  - OBJECTIVE: To explore the effect of inhibiting aquaporin-1 (AQP-1) on
      proliferation and apoptosis of the Hep-2 cell. METHOD: The expression of AQP-1 in
      Hep-2 cell was identified through immunohistochemistry. After using
      acetazolamide, an antagonist of AQP-1, the assay of cell proliferation, apoptosis
      and the expression of AQP-1 were performed by microculture tetrazolium salt(MTT)
      and flow cytometry, TUNEL respectively. RESULT: The expression of AQP-1 is mainly
      found on membrane of Hep-2 cell and the expression is significantly reduced when
      the concentration of acetazolamide is 5 x 10(-5) mol/L. Noteworthily, inhibiting
      AQP-1 by acetazolamide, the rate of cell growth and cell apoptosis significantly
      increases with the time prolong. It showed time-dependent phenomena. There is
      positive relationship obviously between cell apoptosis rate and inhibition rate
      of the AQP-1 protein expression. CONCLUSION: The inhibiting AQP-1 with
      acetazolamide may significantly induce apoptosis of Hep-2 cell. It suggest that
      AQP-1 may be as new target of therapy of laryngeal cancer.

PMID- 17220000
TI  - Metaplasia of chondrocytes into osteoblasts.
AB  - Hypertrophic chondrocytes, commonly considered as terminal cells responsible for
      apoptotic elimination in endochondral osteogenesis, have the potential to switch
      their metabolic role and enter osteoblastic differentiation, based on
      histochemical, immunohistochemical, biochemical and cytological analysis. During
      endochondral osteogenesis, some osteocytes are derived from hypertrophic
      chondrocytes. Also non-hypertrophic chondrocytes are able to transform into
      osteogenic cells, and the bone thus formed is termed "transchondroid bone". In
      this review a summary and discussion of reports on chondrocyte
      transdifferentiation is given.

PMID- 17220001
TI  - DMRT1/Dmrt1, the sex determining or sex differentiating gene in Vertebrata.
AB  - Although the phenomenon of sexual dimorphism is widespread in vertebrates, the
      molecular mechanism of sex-determination is not the same across animal phyla, in
      contrast to other areas of developmental biology. Recent extensive studies,
      however, have given proof of evolutionarily conserved function in genes which
      share a novel DNA binding DM domain, primarily identified in two invertebrate sex
      regulatory genes: doublesex of Drosophila melanogaster and mab-3 of
      Caenorhabditis elegans. Their mammalian autosomal homologue, DMRT1, first
      isolated in humans, was further discovered in genomes of various vertebrate
      species and appears to be involved in similar aspects of sexual development. Its
      precise role is still speculated, thus identification of sex reversal mutations,
      functional studies as well as determination of the sex-specific expression
      profile during embryogenesis are still being undertaken. Is this a sex
      determining rather than a sex differentiating gene? Is it involved in a dosage
      sensitive mechanism? On what level does it function in the hierarchy of the
      sexual regulatory gene cascade? Recent results are discussed in this paper.

PMID- 17220002
TI  - A cytogenetic study on three Chilean species of Chrysomelinae (Coleoptera,
      Chrysomelidae).
AB  - Three species of Chilean leaf beetles were chromosomally analyzed. The endemic
      Araucanomela wellingtonensis displays a male meioformula of 13 + Xyp with 2n = 28
      chromosomes and an asymmetric karyotype with two large autosome pairs and 12
      medium/small pairs of autosomes and sex-chromosomes, a diploid number which had
      not been found among the other species of the subtribe Paropsina sensu lato
      studied to date. Strichosa eburata presents a meioformula of 11 + Xyp, 2n = 24
      chromosomes, as occurs in many species of chrysomelines belonging to different
      subtribes. Furthermore, Phaedon cyanopterum has a 16 + Xyp meioformula, that is
      2n = 34 chromosomes, of small size mostly, also in agreement with the
      karyological findings obtained in all the other congeneric species so far
      examined. These cytogenetic data are discussed with respect to the previous ones
      in this subfamily and with other characters of taxonomic and evolutionary value.

PMID- 17220003
TI  - Roles of thyroid, adrenal and pancreatic hormones on thyroid activity of the soft
      shelled turtles Lissemys punctata punctata Bonnoterre.
AB  - The effects of some exogenous peripheral hormones (thyroxine, corticosterone,
      epinephrine, norepinephrine and insulin) on thyroid activity were investigated in
      juvenile female soft-shelled turtles, Lissemys punctata punctata. Each hormone
      was injected in three different doses (25 microg, 50 microg or 100 microg each
      per 100 g body weight, once daily at 9 AM) for 10 consecutive days. Thyroid
      activity was evaluated by gravimetry, histology (epithelial height) and
      thyroperoxidase assay. The findings revealed that thyroxine in low dose (25
      microg) stimulated thyroid activity by increasing the relative thyroid weight,
      epithelial height and thyroperoxidase activity, but inhibited gland activity at a
      high dose (100 microg) by decreasing the values of all these parameters. The
      medium dose (50 microg) had no significant effect. All other hormones, in all
      doses, significantly decreased thyroid activity by decreasing the values of all
      the parameters. Thyroid responses to exogenous hormones are generally dose
      dependent in turtles. The mechanisms of actions of the hormones administered are
      suggested.

PMID- 17220004
TI  - Resistance of two planarian species to UV-irradiation.
AB  - The aim of this work was to determine the effects of 20, 25 and 30 minute UV
      irradiation periods lambda = 253.5 nm to two planarian species Dugesia tigrina
      (Gir.) and Polycelis felina (Daly.). In vivo, UV light effects have been reported
      to affect intracellular receptors and disrupt simple behaviour. The effects of UV
      rays on mortality and behavior as well as morphological, cytological and
      histological changes in the two planarian species were assessed, and the course
      and the dynamics of regenerative processes were compared between them.
      Experimental populations of Dugesia tigrina and Polycelis felina species were
      maintained in laboratory conditions at room temperature. Mortality, behavioral
      and morphological changes were monitored daily by means of a light
      stereomicroscope. For cytological and histopathological analysis, planarians were
      fixed in Bouine fixative on the first, second, third, fifth and seventh day after
      exposure to UV-irradiation, respectively. They were embedded in paraffin, cut on
      a microtome, stained with toluidin blue and embedded in Canada-balsam. UV-rays
      caused mortality, behavioral, morphological, cytological and histological changes
      in each planarian species. In regeneration of damaged body parts reticular cells
      and neoblasts played the main role. Neoblasts as totipotent cells extremely
      increased in number in the area of damaged tissue, immediately after UV-exposure.
      Dugesia tigrina was more sensitive to UV-rays than Polycelis felina due to
      possession of less pigmented cells. The course of regeneration in both species
      was similar. Most individuals of both species regenerated in 5 to 12 days after
      UV-irradiation.

PMID- 17220005
TI  - The effect of serotonin on epinephrine modulation of transepithelial ion
      transport in isolated frog skin.
AB  - The aim of this study was to examine the effect of serotonin and epinephrine on
      ion transport of isolated frog skin. The addition of serotonin after incubation
      in Ringer solution (RH), bumetanide (BUME), and after initial incubation in
      amiloride and subsequently in RH, reduced hyperpolarization and did not effect
      the mechanosensitivity of frog skin. Following incubation of the frog skin with
      amiloride (AMI), serotonin did not affect the value of hyperpolarization and
      increased mechanosensitivity. The addition of epinephrine (EPI) on frog skin
      incubated in RH and AMI did not affect hyperpolarization, but repeated
      application of this compound after serotonin increased hyperpolarization. After
      incubation with bumetanide, addition of EPI before and after application of
      serotonin did not affect the value of the examined parameters of the frog skin.
      Initial incubation with AMI and later in RH caused a drop in reaction to EPI and
      no effect on mechanosensitivity. Repeated addition of epinephrine in this group
      did not affect the reaction value, while it decreased the reaction value during
      mechanical stimulation. The experimental data presented in this study indicate
      that serotonin inhibits the sodium ion current. Epinephrine inhibits the chloride
      ion current, however, after the application of serotonin, EPI stimulates sodium
      ion transport.

PMID- 17220006
TI  - The electrical potential difference through the foot epithelium of the snail
      Achatina achatina, Lameere during mechanical and chemical stimulation.
AB  - An important electrophysiological variable--the transepithelial potential
      difference reflects the electrogenic transepithelial ion currents, which are
      produced and modified by ion transport processes in polarized cells of
      epithelium. These processes result from coordinated function of transporters in
      apical and basolateral cell membranes and have been observed in all epithelial
      tissues studied so far. The experiments were performed on isolated specimens of
      snail foot. In the experiments, the baseline transepithelial electrical potential
      difference--PD, changes of transepithelial difference during mechanical
      stimulation--dPD and the transepithelial resistance were measured with an Ussing
      apparatus. A total of 60 samples of foot ventral surface of 28 snails were
      studied. The transepithelial electrical potential difference of isolated foot
      ranged from -6.0 to 10.0 mV under different experimental conditions. Mechanical
      stimulation of foot ventral surface caused changes of electrogenic ion transport,
      observed as transient hyperpolarization (electrical potential difference became
      more positive). When the transepithelial electrical potential difference
      decreased during stimulation, the reaction was described as depolarization. When
      amiloride and bumetanide were added to the stimulating fluid so that the sodium
      and chloride ion transport pathways were inhibited, prolonged depolarization
      occurred. Under the influence of different stimuli: mechanical (gentle rinsing),
      chemical (changes of ion concentrations) and pharmacological (application of ion
      inhibitors), transient changes of potential difference (dPD) were evoked, ranging
      from about -0.7 to almost 2.0 mV. Changes in transepithelial potential difference
      of the pedal surface of the snail's foot related to these physiological stimuli
      are probably involved in the locomotion of the animal and are under control of
      the part of the nervous system in which tachykinin related peptides (TRP) act as
      transmitters.

PMID- 17220007
TI  - Occurrence of Paramecium species in Western Siberia, Russia.
AB  - Paramecium strains collected in Central Russia, Western Siberia (the West
      Siberian Lowland and the Altai Mountains in the south) were studied. The presence
      of P. caudatum, P. bursaria, P. multimicronucleatum, P. polycaryum, and four
      species of the P. aurelia complex, i.e. P. primaurelia (in Omsk), P. biaurelia
      (in Krasnoyarsk and the Altai Mountains), P. triaurelia (in Krasnoyarsk), and P.
      pentaurelia (in Novosibirsk, Altai Foreland, and Altai Mountains) was revealed.
      P. triaurelia and P. pentaurelia were found for the first time in Asia.

PMID- 17220008
TI  - Structure traits of Longissimus lumborum muscle in wild boar/domestic pig
      hybrids.
AB  - The structure of musculus longissimus lumborum (m.l.l.) was evaluated with
      respect to proportion of three muscle fiber types and their diameters, in gilts
      and barrows of wild boar/domestic pig hybrids. The experiment was carried out on
      29 hybrids (21 barrows and 8 gilts) which originated from crossing Duroc sows
      with wild boar (Sus scrofa ferus). The diameter of the "red" fibres in barrows
      was 48.42 microm, significantly greater than in gilts--43.71 microm. The
      diameters of the remaining two types of fibres in barrows and gilts were similar
      and amounted to: "intermediate" fibres--39.08 and 40.79 microm, "white" fibres-
      51.42 and 51.03, respectively. In respect to sex no statistical differences in
      proportion of any types of fibers were found, which in barrows came to: "red"-
      12.93%, "intermediate"--30.17% and "white"--57.32%, and in gilts to: 12.50, 27.04
      and 60.45%, respectively. In conclusion, in m.l.l. of wild boar/domestic pig
      hybrids, smaller diameters of all muscle fibers types were identified as well as
      a higher proportion of intermediate fibers in comparison to m.l.l. of various pig
      breeds. An increased proportion of the intermediate fibers probably results from
      the interaction between factors such as age (8-months), physical activity (open
      air for running) and the influence of wild boar genes.

PMID- 17220009
TI  - Lipopolysaccharide aggravates cerebral pathology in B10.PL-derived CD1-/-, beta2m
      /-, TCRalpha-/-, and TCRdelta-/- knockout mice.
AB  - Adult B10.PL-derived immunological genes knockout mice injected with 100 microg
      lipopolysaccharide (LPS) showed severe hydrocephalus and meningitis. A
      consequence of the hydrocephalus is pineal hyperplasia, sponginess of
      periventricular parenchyma, gliosis and, at the last stage of hydrocephalus
      formation, disappearance of the ependymal layer and the Gomori-positive
      subependymal astrocytes. Possible mechanisms for the aggravation of cerebral
      pathology induced by LPS are discussed.

PMID- 17220010
TI  - Analysis of the laying rhythm and reproductive traits of geese.
AB  - The aim of the performed investigations was to analyse the laying rhythm and
      reproductive traits of Koluda white geese from the W11 reproduction strain and to
      determine the heritability of these traits as well as correlations between the
      laying rhythm traits and reproductive traits. The total number of geese
      participating in the experiment included 383 one-year old layers from the control
      flock (the first year of reproductive utilisation). The following traits
      characterizing the laying rhythm were assessed individually for each layer: the
      number of 2 and 3-egg clutches or more, length (in days) of 2- or more egg
      clutches as well as the length of intervals between the laid eggs during the
      entire laying period. The following reproductive traits were also assessed
      individually for each bird: age at sexual maturity, initial number of eggs (eggs
      laid during the period from January, 1st to April, 30th), number of eggs during
      the whole laying period, laying intensity (the total number of eggs x 100/length
      of the laying period in days) as well as the length of the reproductive period.
      It was found that Koluda white geese laid most of their eggs (on average 70.2%)
      singly and not in clutches. With regard to egg clutches, it was found that 2-egg
      clutches constituted 85.3% of eggs laid in clutches. Moderate or high variability
      of traits associated with the laying rhythm and reproduction were demonstrated.
      The observed moderate heritability of the laying rhythm traits indicate that they
      may be utilised in the selection programs for geese. On the other hand, the
      reported high, positive genetic correlation coefficients between the number of
      egg clutches and the initial and total egg number as well as laying intensity
      confirm the existence of interactions between these traits. This fact may be
      helpful in breeding programs for determining the optimal selection systems for
      geese.

PMID- 17220011
TI  - Toxicity of essential oils extracted from Origanum onites L. and Citrus aurentium
      L. against the pine processionary moth, Thaumetopoea wilkinsoni Tams.
AB  - The pine processionary moth (PPM), Thaumetopoea wilkinsoni Tams. (Lepidoptera:
      Thaumetopoeidae), is an important forest pest in the Mediterranean area,
      additionally urticating hairs of the caterpillars of this species cause strong
      allergic reactions on skin of humans and animals. In the present study, essential
      oils extracted from aerial parts of Origanum onites L. and fruit peels of Citrus
      aurentium L. were tested at three doses (0.1, 0.5 and 1%) against 4th and 5th
      instar larvae of the pest. The results showed that the activities were
      concentration dependent. The LD50 and LD90 values were 0.288 and 0.926% for O.
      onites, 0.530 and 2.306% for C. aurentium, respectively.

PMID- 17220012
TI  - Season dependent response of the Marsh frog (Rana ridibunda) to cadmium exposure.
AB  - Cadmium toxicity related to cysteine metabolism and glutathione levels in several
      tissues of the Marsh frog (Rana ridibunda) collected in late spring were
      investigated after exposure to 80 mg CdCl2 L(-1) for 168 h. The results were
      compared to those obtained in a previous experiment carried out in autumn. The
      most striking changes involved the brain which could not maintain a proper
      glutathione level and the testes in which neither GSH nor sulfane sulfur levels
      recovered. Substantial damage is expected in the presence of Cd which decreases
      the antioxidant status of these tissues. It seems that in spring, frogs had
      lesser tolerance for Cd in comparison with frogs in autumn. This may be caused by
      the transition to aerobic respiration after hibernation.

PMID- 17220013
TI  - An examination of pathways from childhood victimization to violence: the role of
      early aggression and problematic alcohol use.
AB  - Using prospective data from a cohort design study involving documented cases of
      child abuse and neglect and a matched control group, we examine two potential
      pathways between childhood victimization and violent criminal behavior: early
      aggressive behavior and problematic drinking. Structural equation models,
      including controls for race/ethnicity, socioeconomic status, parental alcoholism,
      and parental criminality, revealed different pathways for men and women. For men,
      child maltreatment has direct and indirect (through aggressive behavior and
      problematic alcohol use) paths to violence. For women, problematic alcohol use
      mediates the relationship between childhood victimization and violence, and,
      independent of child maltreatment, early aggression leads to alcohol problems,
      which lead to violence. Interventions for victims of childhood maltreatment need
      to recognize the role of early aggressive behavior and alcohol problems as risk
      factors for subsequent violence.

PMID- 17220014
TI  - Adding insult to injury: development and initial validation of the Partner
      Directed Insults Scale.
AB  - Women who are verbally abused by their intimate male partners suffer serious
      mental health consequences and often experience physical violence in their
      relationship. Despite the importance of studying verbal abuse, no previous
      research has investigated the specific content of the insults men use to derogate
      their partners. We present the development and initial validation of a new
      measure designed to assess the specific content of insults used by men against
      their intimate partners. In a preliminary study, we used feedback from battered
      women, along with a review of the relevant literature, to identify specific
      insults for inclusion in the Partner-Directed Insults Scale (PDIS). We
      administered the PDIS to a sample of United States participants (Study 1) and a
      sample of New Zealand participants (Study 2), allowing for a cross-national
      investigation of the specific insults that men use to derogate their partners.
      The results demonstrate the practical need for such a scale and provide evidence
      for the discriminant validity of the PDIS by documenting that men's use of
      insults predicts their use of controlling behaviors and physical violence.

PMID- 17220015
TI  - Gender and multiple forms of peer victimization: how do they influence adolescent
      psychosocial adjustment?
AB  - This study explores the relationship among multiple forms of peer victimization
      (e.g., direct physical/verbal, relational, and sexual harassment) and
      psychosocial adjustment among urban students and uses cluster analysis to
      identify subgroups of victims. Students in sixth, seventh, and eighth grade
      completed self-report surveys about their psychosocial adjustment, peer
      victimization experiences, and the gender of the other person involved. Results
      reveal that both physical/verbal victimization and sexual harassment were related
      to internalizing behavior, and sexual harassment was related to externalizing
      behavior. Cluster analysis revealed preliminary subgroups of victims. In
      addition, being victimized by a boy was more strongly related to behavior
      problems for both boys and girls than the experience of being victimized by a
      girl. Results suggest that the gender of perpetrators and victims should be
      considered, and there is a need to include sexual harassment in the study of peer
      victimization when developmentally appropriate.

PMID- 17220016
TI  - Correlates of comorbid PTSD and polysubstance use in sexual assault victims.
AB  - A diverse sample of community-residing women in a large metropolitan area who had
      experienced adult sexual assault was surveyed using standardized measures in an
      NIAAA-funded study (2003-2004). Four groups (N = 503) of victims: (1) post
      traumatic stress disorder (PTSD)-only, (2) PTSD and illicit drug use, (3) PTSD
      and drinking problems, and (4) PTSD and polysubstance use were compared using
      bivariate analyses. Victims with PTSD/polysubstance use had lower socioeconomic
      status, more extensive trauma histories, worse current psychological functioning,
      more problematic post-assault psychosocial experiences, and more sexual
      revictimization at follow-up than those with PTSD only. Implications for future
      research are discussed.

PMID- 17220017
TI  - Early abuse experiences and subsequent gender differences in couple adjustment.
AB  - The main purpose of the current study was to evaluate the relationship between
      early abusive experiences (sexual abuse, parental violence, and witnessing
      parental violence) and subsequent couple adjustment with a theoretical model that
      incorporates attachment and psychological distress as mediator variables. We
      specifically examined the variability in long-term psychosocial characteristics
      of child abuse survivors across women and men. A representative sample of French
      Canadian couples composed of 632 men and women completed measures of child abuse,
      attachment, psychological distress, and dyadic adjustment. Structural equation
      analyses showed that, for both women and men, sexual abuse was related to dyadic
      adjustment through anxiety about abandonment and psychological distress. For men,
      experiencing physical or psychological violence was associated with dyadic
      adjustment through psychological distress. For women, there was an indirect
      relationship between witnessing physical violence and dyadic adjustment through
      abandonment anxiety. Differences between men and women in the long-term
      adjustment to childhood sexual abuse were small and not consistent with a gender
      specific model of psychosocial repercussions.

PMID- 17220018
TI  - Rape acknowledgment and postassault experiences: how acknowledgment status
      relates to disclosure, coping, worldview, and reactions received from others.
AB  - Many rape victims are unacknowledged. These victims do not label their experience
      as rape; instead they give the experience a more benign label, such as a
      miscommunication. The current study examined the relationship between victims'
      acknowledgment status and post-assault behaviors, moving beyond prior research.
      Analyses of covariance were conducted comparing the post-assault experiences of
      unacknowledged and acknowledged college rape victims (n = 256), controlling for
      differences in victims' assault characteristics, multiple victimization, and post
      traumatic stress symptoms. Results supported that unacknowledged and acknowledged
      victims differed in their coping, disclosure, belief in justice, and receipt of
      egocentric reactions following disclosure. Implications for future work examining
      the dynamic interplay among assault characteristics, sexual scripts,
      acknowledgment status, and post-assault factors are discussed.

PMID- 17220019
TI  - Domestic violence beliefs and perceptions among college students.
AB  - This study builds on current research, investigating the relationships between
      sociodemographic variables and domestic violence attitudes and beliefs among
      college students. Data from the Relationship Characteristics Study conducted in
      2001, which includes a sample of 1,938 college students, are used to replicate
      and extend the research of Carlson and Worden (2001, 2005), the developers of the
      attitudes and beliefs items. In addition, the research portends to analyze
      factors associated with domestic violence causation endorsement, physical and
      sexual abuse, stalking, and verbal abuse beliefs, including gender, race and
      ethnicity, university year, parents' education, family income, parents' marital
      status, and relationship status. Results are consistent with the rates reported
      by the item developers. Further, results demonstrate that sociodemographic
      variables are correlated with physical and sexual abuse and verbal abuse beliefs
      and causation endorsement.

PMID- 17220020
TI  - Inflammatory effects and immune system correlates of rape.
AB  - The purpose of this study was to evaluate the feasibility of measuring stress
      hormones and immunity following rape. The long-term goal is to evaluate the
      predictive value of stress-immune-inflammatory responses to later health
      outcomes. Fifteen women reporting rape were compared with 16 control
      participants. Serum stress hormones, proinflammatory cytokines, acute phase
      proteins, functional assays, and lymphocyte subsets were measured in blood
      samples. Women reporting rape had higher cytotoxic cells, lower B lymphocyte
      counts, higher proinflammatory biomarkers, and decreased lymphocyte proliferation
      compared to the control group. This finding suggests that rape produces
      activation of the innate immunity and suppression of some aspects of adaptive
      immunity. If these immune changes persist, they may contribute to the
      pathophysiology of long-term health sequelae by provoking chronic inflammation
      and decreased cellular immunocompetence.

PMID- 17220021
TI  - [Is there an increase in the incidence of gbs carrier rates among pregnant women
      in northern Israel?].
AB  - BACKGROUND: Group B Streptococci (GBS) asymptomatically colonize the vaginal or
      rectal areas of about 20% of pregnant women (4-40%). About 50% of infants to
      mothers with GBS colonization also become colonized at rectal, umbilical or oral
      sites. GBS is a leading bacterial cause of neonatal illness and death. The
      present prevalence rate of GBS carriers among parturients in the western Galilee
      in Israel is unknown. AIM: A prospective study of the GBS carrier rate according
      to origin and gestational age in the western Galilee in Israel. METHODS: A
      prospective study including 700 pregnant women. All women were screened for
      carriage of GBS by vaginal and rectal cultures. RESULTS: Sixteen percent of the
      parturients were found to be GBS colonized. The prevalence of GBS was 13.7% in
      Jewish women and 19% in Arab women, P=0.038. The women were also divided into two
      groups according to the gestational age one group included 414 women in 24-37
      weeks gestation, and the other group included 286 women in term pregnancy. No
      difference was found in the rate of GBS carriers between the two gestational age
      groups. CONCLUSIONS: In the present study we found a significant increase in the
      incidence of GBS colonization in pregnant women in northern Israel. We also found
      an increased rate of GBS carriers in Arab women relative to Jewish women.

PMID- 17220022
TI  - [Levels of fibrinogen compared to crp in plasma as new marker in diagnosis of
      pulmonary edema of non septic origin].
AB  - INTRODUCTION: Community-acquired pneumonia, that requires hospitalization, is a
      severe illness with high mortality rates, especially in cases of delay of
      appropriate treatment. At times, the correct diagnosis of the disease is
      difficult due to equivocal clinical picture or chest film, accompanying diseases
      that could mask or simulate the pneumonia. THE AIMS OF OUR STUDY WERE: 1. follow
      up levels of fibrinogen throughout hospitalization in the group of patients
      admitted to the hospital due to pneumonia and pulmonary edema of non-infectious
      origin; 2. an estimation opportunity using them as possible new markers for
      diagnosis of pneumonia and for following response to treatment. METHODS: Three
      groups of patients were studied: a group of 15 patients admitted due to
      pneumonia, a group of 15 patients admitted due to pulmonary edema, and a control
      group 15 healthy subjects. The blood samples for white blood cells count,
      erythrocyte sedimentation rates, levels of fibrinogen, C-reactive protein,
      albumin, were taken for each patient on admission, 48 and 72 hours following
      admission and on discharge day. The received dates were compared using Student t
      test. RESULTS: The levels of fibrinogen were higher on admission, in the patients
      with pneumonia, maximally after 48 and 72 hours (P<0.001) in comparison to the
      control group. In pulmonary edema the fibrinogen levels were also high but less
      than those with pneumonia (P=0.0044), with gradual declining throughout
      hospitalization period (P> 0.027 for both groups in discharge day). The
      comparison of fibrinogen levels between groups of patients with pneumonia and
      pulmonary edema reveal statistically significant results at time of admission,
      after 48 and 72 hours but not on discharge day. CONCLUSION: Fibrinogens can be
      used as reliable markers for primary diagnosing of pneumonia or differential
      diagnosis from pulmonary edema, on admission and until 72 hours but not for
      patient follow-up throughout hospitalization period. Additional studies are
      needed for discovering other new markers for patient follow-up throughout
      hospitalization period.

PMID- 17220023
TI  - [The significance of troponin T in hemodialysis patients].
AB  - INTRODUCTION: Troponin T and I are located in the myocardium. Monitoring blood
      Troponin levels is advantageous in evaluating unstable angina over measuring CPK
      MB, previously serving as a "golden standard" for urgent evaluation of myocardial
      infarct. AIM: To measure blood troponin T levels in hemodialysis patients without
      severe cardiovascular events, following its distribution according to various
      risk factors. METHODS: Sera were collected from 68 hemodialysis (HD) patients
      before starting dialysis sessions and compared to 10 age- and gender-matched
      healthy volunteers (NC). Troponin T levels were measured using Troponin T STAT
      Elecsys-Roche kits. RESULTS: Blood Troponin T levels were significantly higher in
      HD patients compared to NC (0.126 +/- 0.016 vs. 0.005 +/- 0 ng/dL, respectively;
      P=0.026). HD patients with ischemic heart disease (IHD) showed significantly
      higher levels of Troponin T, compared to HD patients without IHD (0.17+/-0.036
      vs. 0.081 +/- 0.015 ng/dL, respectively; P=0.012). Diabetic (DM) HD patients
      showed higher levels of Troponin T, compared to non-DM HD patients (0.168+/-0.034
      vs. 0.068+/-0.012 ng/dL, respectively; P= 0.002). CONCLUSION: Troponin T may
      efficiently serve as a diagnostic, monitoring and prognostic parameter in HD
      patients.

PMID- 17220024
TI  - [Severe hypercapnia in asthmatic attack].
AB  - This is an unusual case, of an adult man who was hospitalized with a severe
      asthmatic attack and severe hypercapnia, refractory to intensive medical
      treatment, which responded to pressure mechanical ventilation. We advise to
      consider this mode of treatment in similar cases.

PMID- 17220025
TI  - [Catheter lock solution--taurolock for prevention of catheter-related bacteremia
      in hemodialysis patients].
AB  - BACKGROUND: Bacteremia and thrombosis are the major complications of tunneled
      cuff central vein catheters (TCC) used for haemodialysis. Bacterial biofilm is
      the source of catheter related bacteremia (CRB). Instillation of catheter lock
      solution (CLS) containing antibiotic-anticoagulant solution can cure and prevent
      CRB. The aim of this publication is to report our experience with the use of CLS 
      TauroLock (Taurolidine and 4% citrate) in the prevention of catheter related
      bacteremia in hemodialysis patients. METHODS: Thirteen patients with TCC on
      chronic hemodialysis were included in the study. Group A: 5 patients with
      previous inserted catheters and history of at least one bacteremia episode before
      the study. Group B: 8 patients with new catheters. At the end of each dialysis
      the catheters were locked with TauroLock until the next dialysis session.
      RESULTS: In Group A, the catheter related bacteremia (CRB) was reduced from 9.5
      episodes?1000 patients days prior to the study to 1.15 episodes?1000 patients
      days through 867 days of treatment. In Group B, there were not any CRB during
      1179 treatment days in the 8 patients. Due to catheter patency problems, 2500 IU
      of heparin was added to the TauroLock solution in 3 patients (60%) of group A and
      in 7 patients (87.5%) of group B and Urokinase instillation in 1 and 3 patients
      of group A and B respectively. CONCLUSION: The catheter lock solution TauroLock
      significantly decreased the rate of CRB in HD patients with TCC, to complete
      prevention in new TCC. Addition of heparin to the TauroLock solution should be
      considered to maintain catheter patency.

PMID- 17220026
TI  - [Osteoid osteoma of the wrist joint resembling tenosynovitis].
AB  - Osteoid osteoma of bones of the wrist joint is a relatively rare lesion. This
      article presents a series of three patients, one with osteoid osteoma of the
      styloid process of the radius and two with osteoid osteoma of the capitate bone.
      All of them had clinical symptoms resembling those of stenosing tenosynovitis of
      the wrist joint. X-rays, tomography and bone scan revealed the characteristic
      findings of osteoid osteoma. Histological examination confirmed the diagnosis.
      Treatment consisted of "en bloc" excision of these tumors. Following surgery
      patients were asymptomatic and had normal mobility of the affected wrist. In the
      first patient this has been maintained for the succeeding 27 years. It is
      suggested that in any case of persistent unexplained pain of the wrist or
      clinical symptoms resembling those of tenosynovitis, osteoid osteoma of the
      styloid process of the radius or of the carpal bones should also be included in
      the differential diagnosis. The recommended treatment of osteoid osteoma is "en
      bloc" excision of this tumour in the affected bone, resulting in complete relief
      of pain and absence of functional disturbances.

PMID- 17220027
TI  - [Clinical, biochemical and molecular characterization of rare genetic disorders,
      related to nucleotide excision repair (NER) system].
AB  - All living organisms are equipped with DNA repair systems that can cope with a
      wide variety of DNA lesions. Among these repair pathways, nucleotide excision
      repair (NER) is quite versatile, involved in the removal of a variety of bulky
      DNA lesions induced by ultraviolet light and chemical carcinogens and mutagens.
      The importance of NER for human health is illustrated mainly by the occurrence of
      rare life-threatening disorders such as Xeroderma Pigmentosum (XP), Cockayne
      Syndrome (CS) and Trichthiodystrophy (TTD). XP, CS and most TTD patients exhibit
      increased sensitivity to UV light and premature aging. XP is associated with a
      high incidence of skin tumors, CS is primarily a developmental disorder
      associated with failure to thrive, and psychomotor retardation. The authors
      report the clinical, biochemical and molecular aspects of the NER pathway in
      individuals suspected to have a DNA repair, NER type-related disease. These
      diseases are rare worldwide, but are frequent in Israel, probably due to the high
      rate of consanguinity among certain Arab, Druze and Jewish populations. Our
      laboratory is the only one in Israel, and one of very few labs world-wide that is
      performing DNA repair evaluation as a diagnostic test for DNA repair-deficient
      inherited diseases. Identification of the causative genes and proteins in
      suspected families will facilitate accurate diagnosis, genetic counseling,
      identification of couples at risk and prenatal diagnosis.

PMID- 17220028
TI  - [The effect of calcium channel blocker lercanidipine on lowgrade inflammation
      parameters in essential hypertension patients].
AB  - INTRODUCTION: Oxidative stress (OS), inflammation and insulin resistance are
      among the mechanisms that have been recently implicated in pathogenesis of
      essential hypertension (EH). Peripheral polymorphonuclear leukocytes (PMNLs) are
      primed in EH patients, releasing uncontrolled superoxide anion contributing to OS
      and chronic low-grade inflammation in these patients. PMNL priming correlates
      with insulin resistance and with PMNL intracellular calcium ([Ca2+]i). Recent
      studies have attributed additional anti-oxidative characteristics to the anti
      hypertensive drug Lercanidipine (Vasodip), a third generation calcium-channel
      blocker. AIM: To evaluate possible novel effects of two months of Lercanidipine
      treatment on systemic and PMNL-related inflammation and on insulin resistance in
      EH patients. METHODS: Fifteen non-smoking EH patients with untreated mild to
      moderate high blood pressure (BP) and age- and gender-matched healthy controls
      (HC) were included in the study. Low-grade inflammation was expressed by PMNL
      counts and apoptosis, by plasma fibrinogen, CRP and albumin (as a negative acute
      phase reactant) levels. Fasting serum insulin levels served as a marker of
      insulin resistance. RESULTS: Inflammation parameters and insulin levels were
      higher in EH compared to HC. PMNL counts, fibrinogen and insulin levels
      positively correlated with mean arterial blood pressure values. Two months of
      Lercanidipine treatment showed a significant decrease in BP, PMNL counts and
      apoptosis, CRP and serum insulin levels and a significant increase in serum
      albumin levels. CONCLUSION: The authors imply that the low-grade systemic
      inflammation and insulin resistance detected in EH patients may be attenuated by
      the use of Lercanidipine, adding new unknown anti-inflammatory properties to this
      calcium channel blocker.

PMID- 17220029
TI  - [Polymorphonuclear leukocyte priming and counts are in correlation with blood
      pressure parameters].
AB  - BACKGROUND: In hypertensive patients, the polymorphonuclear leukocytes (PMNLs)
      are primed, concomitantly contributing to oxidative stress and chronic low-grade
      inflammation. Furthermore, in the Sabra rat model of salt-induced hypertension,
      priming of PMNLs, oxidative stress and inflammation antecede the development of
      hypertension. In the present study we tested the hypothesis that PMNL priming and
      PMNL and white blood cells (WBC) counts are interrelated with blood pressure
      values. Therefore, we have evaluated the correlation between WBC and PMNL counts,
      PMNL priming parameters and blood pressure in untreated essential hypertension
      patients (EH) and age and gender healthy controls. METHODS: Diastolic blood
      pressure (DBP), systolic blood pressure (SBP) and mean arterial pressure (MAP)
      values were correlated by linear regression analysis with the rates of superoxide
      release from separated PMNLs and with WBC and PMNL counts. RESULTS: The rate of
      superoxide release from PMNLs was higher in EH patients compared to their healthy
      controls. The rate of superoxide release from PMNLs correlated with SBP, DBP and
      MAP. WBC and PMNL counts were all significantly correlated with blood pressure
      values. CONCLUSION: The results of the study offer an additional mechanism
      involving primed PMNLs and elevated PMNL counts in the pathogenesis of
      hypertension and its late cardiovascular complications.

PMID- 17220030
TI  - [Limb fractures in organ transplanted patients].
AB  - Patients that have had organ transplantation receive immunosuppressive therapy to
      prevent organ rejection. Along with this therapy comes a higher incidence of
      osteoporosis, which may lead to an increased frequency of fractures in post
      transplant patients. This article presents three patients who underwent organ
      transplantation and had subsequent fractures: subcapital fracture of the femoral
      neck treated with hemiarthroplasty of the hip, in a patient 8 years post cardiac
      transplantation; minimally displaced intertrochanteric fracture treated by
      percutaneous pinning, in a patient one year post lung transplantation; minimally
      displaced subcapital fracture treated by percutaneous pinning, in a patient 3
      months post liver transplantation. Each patient was operated upon successfully
      and without complications. The three patients were able to resume their
      activities of sitting and walking after only a few days. In our opinion,
      preventive treatment for osteoporosis is crucial for candidates of solid organ
      transplantation. This treatment should be initiated prior to surgery and
      continued after as well. Transplant patients receiving immunosupression therapy
      with subsequent osteoporotic fractures of the extremities should undergo early
      surgical intervention in order to enable a short and quick rehabilitation and
      early return to normal activities of daily living.

PMID- 17220031
TI  - [Support as an impetus for helping women cope with breast cancer].
AB  - Breast cancer is the most common malignant illness in Israel and the western
      world; it accounts for 30% of all women with cancer. The woman suffering from
      breast cancer confronts and experiences surgery, loss, and long-term treatment
      that necessitate strenuous coping on her part, both physically and mentally. This
      research study examined the correlation between the degree of support that
      Jewish, Arab, and immigrant women from the former Soviet Union, who have cancer
      and live in the Galilee area of Israel, receive from their immediate surroundings
      especially from their husbands, families, friends, and the healthcare treatment
      staff, and their ability to cope with the illness. This study was a quantitative,
      correlative-prospective study and was conducted using an anonymous self-reporting
      questionnaire comprised of 50 questions ranked according to the Likert scale from
      1 (never) to 5 (always). The questionnaire was distributed to 45 women with
      breast cancer and all of the participants completed and returned the
      questionnaires for analysis. FINDINGS: The findings showed a weak, positive, and
      significant correlation between the support that a woman received and her
      emotional coping with the illness; the average variable was 2.36, standard
      deviation was 0.94, the median was 2.33. There was a significant difference in
      the degree of support that Jewish women received; it was greater than the support
      that Arab women received (Jewish women SD=0.74, M=3.87; Muslim women SD=0.38, M =
      3.32). Women from the former Soviet Union received more support from their
      husbands than Israeli-born women. The findings show that husbands are a major
      source of support for women who cope with breast cancer and the treatment staff
      is a more significant source of support than friends. RECOMMENDATIONS: The
      authors believe that this study can contribute in shaping new treatment
      strategies for women with breast cancer treated at the Western Galilee hospital
      in Nahariya. Since there is a paucity of comparative research based on ethnicity
      and national origin, in Israel and throughout the world, related to how women
      with cancer cope, it is possible that this study can assist the Israeli
      healthcare system on a national scale to reconsider its treatment policy for
      breast cancer patients.

PMID- 17220032
TI  - [Western Galilee Hospital in Nahariya--50+ years].
AB  - Initially beginning as a small birthing center, the Western Galilee Hospital
      (WGH) in Nahariya is now the largest hospital in Galilee. It serves a
      demographically mixed Israeli population of more then 400,000, the Galilee's
      mosaic of Jews, Moslems, Christians, Druze and large immigrant populations from
      the former Soviet Union and Ethiopia. The hospital is also a treatment center for
      IDF and UN soldiers. The staff, which reflects the ethnically mixed population of
      the region, is a long-standing model of cooperation and peaceful coexistence.
      Doctors and nurses of different faiths and cultural backgrounds work together in
      harmony and with respect to achieve a mutual goal: to provide the best and finest
      medical treatment to all in need. The hospital's proximity to the Lebanese
      border, together with its previous experience as the target of Katyusha rocket
      fire, has forced management to construct underground facilities for emergency
      situations. Five-hundred beds and eight modern operating rooms that are fully
      protected from conventional, biological and chemical warfare are an integral part
      of the preparedness program. The entire staff participates in preparatory drills
      for mass casualty events. WGH is a forerunner in quality of medical care. To date
      it is the only Israeli hospital to meet the demanding standards for ISO 9000 2000
      certification for quality management, and has now adopted the standards of the
      European Federation of Quality Management (EFQM). The hospital won the Rabin
      National Award for Quality in 1995.

PMID- 17220033
TI  - [Prenatal diagnosis for chromosomal abnormality: time to change the Israeli
      policy].
AB  - Down syndrome is the most common serious chromosomal abnormality among live
      births. Safe, inexpensive, and accurate prenatal screening, with a high detection
      rate (DR) and low false positive rate (FPR) is needed for prevention. Second
      trimester screening, based on three maternal serum markers (free betaHCG, uE3,
      AFP) has a 59-75% DR with a 5% FPR. The addition of Inhibin-A to this panel
      (Quadruple test), increases DR to 70-85%. First trimester screening combining two
      serum markers (free betaHCG, PAPP-A), with ultrasound nuchal translucency (NT)
      has a 80-90% DR, allows reassurance or early diagnosis and pregnancy termination
      in a relatively simple and safe technique. Testing sequentially in both
      trimesters (NT, PAPP-A, then Quadruple markers), but withholding results until
      all markers are measured, allows a 92-94% DR with a low FPR, although the
      clinical and human advantages of early testing are lost. Three alternative
      approaches are presented in this review, which achieve a high DR and low FPR
      without this disadvantage. Based on recently published data, we propose a change
      in the current policy practiced in Israel whereby women above 35 are referred for
      invasive prenatal diagnosis paid by the government. Instead, awareness of modern
      screening methods should be enhanced and invasive diagnosis only offered to women
      whose risk based on screening exceeds an agreed cutoff. This would achieve better
      and safer prevention acceptable to a wide spectrum of ethnicities, religions and
      cultures in Israeli society, at a reasonable cost to the public health system in
      Israel.

PMID- 17220034
TI  - [Cycling after operation for total hip or total knee replacement].
AB  - Relatively few elderly people used to practice intensive and competitive sports
      activities. Following operations on joints of the lower extremity, such as total
      hip or knee replacement, most patients decrease their physical activity.
      Sometimes they are even unable to walk without an assisting device. The
      activation of the hip joint articulation among cyclists is very restricted, since
      the pelvis does not have practically any mobility. Lowering of the pedal, which
      requires the more important effort, is carried out by the extensors of the hip,
      but especially by those of the knee as well as the foot flexors. In cycling, the
      load on the articulations of the hips is practically reduced, in spite of the
      great effort. The load placed by the body weight on the hip joint, even in
      ascents, is reduced during this exercise, though the risk of prosthesis loosening
      is apparently very small. Knee joints are much more engaged during biking, but it
      is still considered as low-impact sport, compared to weight-bearing activities
      such as jogging and even walking.

PMID- 17220035
TI  - [Theory of mind in schizophrenia].
AB  - The term "theory of mind" (ToM) refers to the capacity to infer one's own and
      other persons' mental states (e.g. their beliefs, feelings, intentions or
      knowledge). It was found that children in the autistic spectrum have deficits in
      ToM. One of the suggestions was that unlike autistic people, ToM skills are
      normally developed in schizophrenia patients, but "lost" in the first psychotic
      episode. The deficit may disappear on remission from the acute phase, as
      described in some studies. A substantial body of research has highlighted the
      impaired ToM in schizophrenia. There is good empirical evidence that ToM is
      specifically impaired in schizophrenia and that many psychotic symptoms--for
      instance, delusions of alien control and persecution, the presence of thought and
      language disorganization, and other behavioral symptoms--may best be understood
      in light of a disturbed capacity in patients to relate their own intentions to
      executing behavior, and to monitor others' intentions. However, it is still under
      debate how an impaired ToM in schizophrenia is associated with other aspects of
      cognition, how the impairment fluctuates with acuity or chronicity of the
      schizophrenic disorder, and if it is a state or trate marker. The paper reviews
      the current literature and suggests potential implications and future research
      areas.

PMID- 17220036
TI  - [Bacteria: able to learn and adapt. Disease pathogens protect themselves through
      various resistance mechanisms].

PMID- 17220037
TI  - [Pharmacotherapy of obesity].
AB  - Long-term success in obesity therapy is difficult to obtain, therefore drug
      therapy appears to be helpful. Until today, end-point studies for obesity drugs
      beyond the improvement of individual surrogate parameters are still missing. For
      all available drugs, medical treatment can be recommended only for a limited
      period of time due to the data of the studies and under consideration of side
      effects. Although a weight reduction leads to an improvement of cardiovascular
      risk factors and hence a reduction of cardiovascular morbidity and mortality
      should be expected, no study could prove it so far. Despite the positive
      influence on individual surrogate parameters, the use of the present available
      therapies appears underwhelming. In this overview the approved substances and
      perspectives of new therapeutic concepts are represented.

PMID- 17220038
TI  - [Rational use of oral antibiotics in adults and school children (children above 6
      years). Findings of an expert commission of the Paul Ehrlich Society for
      Chemotherapy. V].

PMID- 17220039
TI  - [Honey for wound healing?].

PMID- 17220040
TI  - [Alternative therapy for menopausal complaints].

PMID- 17220042
TI  - [Protection by dietary fiber from colorectal cancer?].

PMID- 17220041
TI  - [Green tea for reduction of plaque development].

PMID- 17220043
TI  - [Local chemotherapy for brain tumors].

PMID- 17220044
TI  - [Actions and safety of a 7-valent pneumococcal vaccine].

PMID- 17220045
TI  - [Dental amalgam in children. Little indication of neurologic or renal damage].

PMID- 17220047
TI  - [Diabetes mellitus type 2. A basic text for preventive measures].

PMID- 17220046
TI  - [Metabolic syndrome. What is the definition in practice?].

PMID- 17220048
TI  - Bioequivalence study of two losartan formulations administered orally in healthy
      male volunteers.
AB  - The bioavailability of a new losartan preparation (2-butyl-4-chloro-1-[p-(o-1H
      tetrazol-5-ylphenyl)benzyl]imidazole-5-methanol monopotassium salt, CAS 114798-26
      4) was compared with the reference preparation of the drug in 24 healthy male
      volunteers, aged between 19 and 32. The open, randomized, single-blind two
      sequence, two-period crossover study design was performed. Under fasting
      conditions, each subject received a single oral dose of 100 mg losartan as a test
      or reference formulation. The plasma concentrations of losartan and its active
      metabolite were analyzed by a rapid and sensitive HPLC method with UV detection.
      The pharmacokinetic parameters included AUC0-36h, AUC0-infinity, Cmax, t1/2, and
      Ke. Values of AUC0-infinity demonstrate nearly identical bioavailability of
      losartan from the examined formulations. The AUC0-infinity of losartan was
      2019.92+/-1002.90 and 2028.58+/-837.45 ng x h/ml for the test and reference
      formulation, respectively. The AUC0-infinity of the metabolite was 10851.52+/
      4438.66 and 11041.18 +/-5015.81 ng x h/ml for test and reference formulation,
      respectively. The maximum plasma concentration (Cmax) of losartan was 745.94+/
      419.75 ng/ml for the test and 745.74+/-329.99 ng/ml for the reference product and
      the Cmax of the metabolite was 1805.77+/-765.39 and 1606.22 +/-977.22 ng/ml for
      the test and reference product, respectively. No statistical differences were
      observed for Cmax and the area under the plasma concentration-time curve for both
      losartan and its active metabolite. 90 % confidence limits calculated for Cmax
      and AUC from zero to infinity (AUC0-infinity) of losartan and its metabolite were
      included in the bioequivalence range (0.8-1.25 for AUC). This study shows that
      the test formulation is bioequivalent to the reference formulation for losartan
      and its main active metabolite.

PMID- 17220049
TI  - Phase III long-term study and comparative clinical study of nipradilol ophthalmic
      solution in patients with primary open-angle glaucoma and ocular hypertension.
AB  - Nipradilol (CAS 81486-22-8) is a non-selective beta-blocker with alpha-1 blocking
      and nitroglycerin-like vasodilating activities. In the present communication, the
      long-term efficacy and safety of nipradilol were investigated and the efficacy,
      safety and utility of topical nipradilol and timolol (CAS 91524-16-2) were
      compared in patients with primary open-angle glaucoma or ocular hypertension. In
      the long-term study, nipradilol for 1 year (52 weeks) was performed by
      registration method. 67 out of 68 patients were subjected to analysis and 57
      patients (83.8 %) completed 52-week instillation. 0.25 % nipradilol was applied
      twice daily to patients. As a result, intraocular pressure (IOP) decreased
      significantly by 4.0 mmHg to 4.8 mmHg compared with the baseline without
      tachyphylaxis. The incidence of adverse events was 12.5 % at 52 weeks by analysis
      with Kaplan-Meier life-table method. It showed no significant trend of increase
      after 3 months. In the multi-centered double-masked comparative randomized study,
      0.25 % nipradilol was assigned to 96 patients and 0.5 % timolol to 100 patients.
      Each patient was instilled nipradilol or timolol twice daily for 8 weeks. IOP
      significantly decreased by 4.2 mmHg and by 4.7 mmHg at 8 weeks and the incidence
      of adverse events was 10.5 % and 12.1 % in the nipradilol and timolol group,
      respectively. No significant between-group difference in IOP reduction or
      incidence of adverse events was seen. Topical nipradilol showed long-term ocular
      hypotensive effects and clinical safety in a 52-week study, and its efficacy and
      safety equivalent to timolol was confirmed in a 8-week comparative study.

PMID- 17220050
TI  - Effect of food on bioavailability of a single oral dose of clopidogrel in healthy
      male subjects.
AB  - OBJECTIVE: The present study aimed at investigating the effects of concomitant
      food intake on the bioavailability of a single oral dose of clopidogrel (CAS
      113665-84-2). METHODS: Clopidogrel was given under two conditions separated by a
      14-day washout period: fasted and fed (after a standardized high fat breakfast).
      Concentrations of clopidogrel in plasma were quantified by a validated liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) with positive ion electro
      spray ionization using multiple reaction monitoring (MRM). Pharmacokinetic
      parameters such as Cmax, Tmax, AUC0-t, AUC0-inf and tl/2z were estimated using a
      noncompartmental model. RESULTS: The pharmacokinetic parameters were
      significantly affected by food intake. Specifically, Cm, and AUC0-inf of
      clopidogrel increased 6.1-fold and 9.2-fold, respectively, in the fed condition
      compared to the fasted condition. The t1/2 increased from 2.5 h in the fasted
      state to 5.0 h in the fed state. The limit of quantification was 5 pg/mL for
      plasma clopidogrel analysis. CONCLUSION: Food substantially enhanced the
      bioavallability of clopidogrel in healthy subjects.

PMID- 17220051
TI  - Bioequivalence evaluation of two rosiglitazone tablet formulations.
AB  - A randomized, two-period, two-sequence, crossover study was conducted on 28
      healthy male volunteers to compare the bioavailability of two rosiglita-zone (CAS
      122320-73-4) tablet formulations, a test and a commercially available original
      preparation (reference), under fasting conditions. The two preparations were
      given in a dose of 8 mg with a 7-day washout period between the two preparations.
      Eighteen blood samples were collected over 24 h, plasma rosiglitazone
      concentrations were determined by locally validated high performance liquid
      chromatography (HPLC) assay, and pharmacokinetic parameters were analyzed by the
      standard non-compartmental method. The mean+/-SD of AUC0-->t, AUC0-->infinity,
      Cmax, Tmax, and t1/2 were 4.80+/-1.89 and 4.76 +/-1.94 microg x h/ml, 5.17+/-2.11
      and 5.08 +/- 2.27 microg x h/ml, 0.93+/-0.24 and 0.99+/-0.34 microg/ml, 1.0 +/
      0.4 and 0.8+/-0.5 h, and 5.0+/-2.0 and 5.0+/-2.0 h for the test and reference
      formulation, respectively. ANOVA did not show significant formulation, period, or
      sequence effect for any of the pharmacokinetic parameters. The 90 % confidence
      intervals of the mean differences between log-transformed values of the two
      formulations were 93.09 % to 109.73 %, 94.04 % to 111.70 %, and 89.70 % to 103.24
      % for AUC0-->t, AUC-->infinity, and Cmax, respectively. It is concluded that the
      two formulations are equivalent in relation to the rate and extent of absorption.

PMID- 17220052
TI  - Synthesis, stability studies, anti-inflammatory activity and ulcerogenicity of
      morpholinoalkyl ester prodrugs of niflumic acid.
AB  - In search for potential prodrugs for anti-inflammatory drug candidates in the
      niflumate series, novel morpholinoalkyl ester prodrugs of niflumic acid (CAS 4394
      00-7) 5a-b were prepared by esterification of appropriate morpholinylalkyl
      alcohols 3a-b with niflumic acid 4 in the presence of dicyclohexyl carbodiimide
      (DCC) and catalyst dimethylamino pyridine (DMAP) at 0-5 degrees C. The structures
      were confirmed by elemental and spectral data (UV, IR, 1H-NMR, 13C-NMR, and EI
      MS). The ester prodrugs 5a-b showed better solubility than the parent drug
      niflumic acid 4 in simulated gastric fluid (SGF) and phosphate buffer (pH 7.4).
      The in vitro hydrolysis studies were conducted at pH 1.3 (SGF), phosphate buffer
      (pH 7.4) and in human plasma diluted with phosphate buffer (pH 7.4) at 37+/-0.5
      degrees C using HPLC with UV detection. The ester prodrugs 5a-b were
      quantitatively hydrolyzed to the parent drug niflumic acid 4 by enzymatic and/or
      chemical means. It is observed that an increase in the carbon chain length
      rendered the prodrugs 5a-b more stable in phosphate buffer (pH 7.4) than in pH
      1.3 (SGF), but they were rapidly hydrolyzed in human plasma at 37+/-0.5 degrees
      C. They exhibited longer hydrolytic half-lives of 16.11-53.30 h in aqueous buffer
      solutions (pH 1.3 and 7.4) and 1.63-2.73 min in human plasma, respectively. The
      title compounds were evaluated in vivo for anti-inflammatory activity in
      carrageenan induced rat paw oedema model in rats at the doses 45, 90, 150 mg/kg
      b.w. The test compounds exhibited good anti-inflammatory activity (46.6-53.2 % at
      the dose of 150 mg/kg b. w.) with respect to niflumic acid (78.7 % at the dose of
      90 mg/kg b.w.). The compounds were also screened for in vivo ulcerogenicity, it
      was observed that the prodrug 5b was significantly less irritating to gastric
      mucosa than compound 5a and the parent drug niflumic acid 4 following single and
      chronic oral administration in rats.

PMID- 17220053
TI  - Ligand-based design, synthesis and primary in vivo screening of pyrrole
      derivatives as potential tricyclic anti-inflammatory agents.
AB  - Twelve new compounds were designed as 5-aryl-1H-pyrrole analogs of celecoxib (CAS
      169590-42-5) and were synthesized by Paal-Knorr cyclization in three series
      according to 1H-substitution: derivatives with salicylic acid, pyrazolone or
      isonicotinamide residues. The average physico-chemical and steric similarity
      between the prototype and the new analogs (completed with two previously
      synthesized related products) was assessed to be 82 % and therefore considered as
      a reliable prerequisite for spatial compatibility and effective binding to the
      cyclooxygenase (COX) enzymes. The anti-inflammatory effects were determined in
      acute inflammation model using the carrageenan-induced rat paw edema assay on
      male Wistar rats (180-200 g) at doses of 10, 20 and 40 mg/kg, i.p. Six of the new
      products showed higher percent of inhibition (up to 100 %) compared to the highly
      selective COX-2 inhibitor celecoxib and the nonselective indometacin (CAS 53-86
      1) used as reference compounds. Ethyl 1-(1,5-di-methyl-3-oxo-2-phenyl-2,3-dihydro
      1H-4-pyrazolyl)-2-methyl-5-phenyl-1H-3-pyrrolecarboxylate (2b), ethyl 5-(4-chlor
      ophenyl)-2-methyl-1-[(4-pyridylcarbonyl) amino]-1H-3-pyrrolecarboxylate (3c) and
      5-[3-acetyl-2-methyl-5-(4-methylphenyl)-1H-1-pyrrolyl] -2-hydroxybenzoic acid
      (4b) were pointed out as the most active representatives of each of the three
      tested sub-series.

PMID- 17220054
TI  - Effect of sodium fluoride administration to rats on bone phosphorous content and
      phosphatemia.
AB  - Fluoride (F) has a known mitogenic effect on bone cells. The daily administration
      of 40 micromol NaF per 100 g of body weight (bw) increases bone mass in rats.
      Nevertheless, the quality and composition of bone formed under F stimulus is
      still matter of study. The objective of this work was to investigate the effect
      of sodium fluoride (NaF, CAS 7681-49-4) administration on phosphate metabolism
      and its impact on bone. Experiments were carried out in female fasted 50-day-old
      rats. Unless otherwise stated, NaF dose was 40 micromol NaF/day . 100 g bw,
      administered by gastric tube. Four groups of 4 rats each were given the following
      daily NaF doses: Group A: 0, B: 20, C: 40 and D: 60 micromol NaF/day x 100 g bw.
      After 30 days rats were killed saving their femora and plasma. Bone phosphorous
      contents (BPC) and phosphatemia (mg/dl) were measured. BPC decreased
      significantly as a function of NaF dose. A: 93.3+/-14.1; B: 78.7+/-15.5; C:
      61.1+/-14.7**; D: 59.6+/-8.6 **mg P/g dry bone (** significant difference to
      group A, p < 0.01). Phosphatemia (mg/dl) increased significantly with a peak at
      90 min after NaF dose (basal: 5.34+/-0.06; 90 min: 8.15 +/-0.43, p < 0.001).
      Phosphaturia (microg/min) increased though differences were not significant
      (basal: 46.7+/-42.8; 4 h: 1275 +/-757, p > 0.05). In thyroparathyroidectomized
      rats, plasma phosphate increased continuously for at least 240 min. Renal
      plasmatic flow, glomerular filtration rate and renal blood flow were not affected
      by NaF treatment. In isolated perfused rat kidneys, urinary phosphate excretion
      remained unaffected after NaF administration. Phosphate concentration was
      measured in the plasma and erythrocytes of rats after one dose of NaF (n = 8).
      Phosphate content of erythrocyte was not affected by NaF, in spite of the
      concurrent increase in phosphatemia. It is concluded that the treatment with NaF
      causes a transitory increase in plasma phosphate levels. Neither renal
      hemodynamic factors nor the inhibitory effect on parathormone actions appear to
      be the causes of hyperphosphatemia. Efflux of phosphate from cells might not be
      the cause of the increase in phosphatemia. The loss of phosphorous from bone
      appears as the most probable determinant of hyperphosphatemia after fluoride
      administration.

PMID- 17220055
TI  - It is (sort of) a boy and (sort of) a girl. You have (sort of) a say and you
      (sort of) don't? The uneasiness of genital restoration surgery.

PMID- 17220056
TI  - Newborn screening for congenital hypothyroidism.
AB  - Most neonates born with congenital hypothyroidism (CH) have normal appearance and
      no detectable physical signs. Hypothyroidism in the newborn period is almost
      always overlooked and delayed diagnosis leads to the most severe outcome of CH,
      mental retardation, emphasizing the importance of neonatal screening. Blood spot
      T4 or TSH or both can be used in neonatal screening for CH. The latter, which is
      more sensitive, is not cost effective, so the first two are used in different
      programs in the world. TSH screening was shown to be more specific in the
      diagnosis of CH; T4 screening is more sensitive in detecting newborns especially
      with rare hypothalamic-pituitary hypothyroidism, but less specific with a high
      frequency of false positives mainly in low birth weight and premature infants.
      The time at which the sample is taken may vary between centers, with the majority
      taking blood from a heel prick after 24 hours of age to minimize the false
      positive high TSH due to the physiological neonatal TSH surge that elevates TSH
      levels and causes dynamic T4 and T3 changes in the first 1 or 2 days after birth.
      Early discharge of mothers postpartum has increased the ratio of false positive
      TSH elevations. Although transient hypothyroidism may occur frequently, all
      suspected infants should be treated as having CH for the first 3 years of life,
      taking into account the risks of mental retardation. A reevaluation after 3 years
      is needed in such patients. The goal of initial therapy in CH is to minimize
      neonatal central nervous system exposure to hypothyroidism by normalizing thyroid
      function, as reflected by T4 and TSH levels, as rapidly as possible. Iodine
      deficiency is the most important cause of CH worldwide. Iodine is essential for
      thyroid hormone synthesis and is present in soil, water and air. Prevention of
      iodine deficiency can be by iodized salt, iodized oil, iodized bread or iodine
      tablets.

PMID- 17220057
TI  - The adrenal life cycle: the fetal and adult cortex and the remaining questions.

PMID- 17220058
TI  - Persistent high activity of the fetal adrenal cortex in preterm infants: is there
      a clinical significance?
AB  - BACKGROUND: In preterm infants, the activity of the fetal adrenal cortex
      continues until term. Dehydroepiandrosterone sulphate can block the synthesis of
      surfactant in vitro. The incidence of pulmonary disease is higher in male than in
      female preterm infants. OBJECTIVE: To investigate the relationship between
      urinary excretion of fetal zone steroids (3beta-OH-5-ene-steroids) and the
      severity of lung disease in preterm infants with respect to gender. PATIENTS AND
      METHODS: 3beta-OH-5-ene-steroids were profiled by gas chromatography-mass
      spectrometry in 24-h urinary samples in 61 preterm infants of less than 30 weeks
      gestational age. RESULTS: The incidence of respiratory distress syndrome treated
      with surfactant in females (n = 30) was 47% and in males (n = 31) 71%, p = 0.07.
      Medians of total excretion rates of fetal zone steroids (microg/kg/d) in female
      (male) preterm infants were at day 1: 1,317 (895); day 2: 3,154 (7,723), p =
      0.03; day 3: 5,502 (9,494), p = 0.08; day 5: 7,140 (10,407); week 2: 8,731
      (9,720); week 3: 8,571 (10,079); week 4: 7,620 (7,825). Regression analysis did
      not reveal a significant influence of maximum excretion rates of fetal zone
      steroids or gender on the incidence of respiratory distress syndrome treated with
      surfactant. CONCLUSIONS: Excretion rates of fetal zone steroids were 4-fold
      higher than previously reported indicating a persistent high activity of the
      fetal adrenal zone in preterm infants. Excretion rates of fetal zone steroids
      were significantly higher in male preterm infants compared to females at day 2
      (trend at day 3) but did not have a significant influence on the incidence of
      respiratory distress syndrome.

PMID- 17220059
TI  - Growth hormone-IGF-I axis and growth velocity in Chinese children with type 1
      diabetes mellitus.
AB  - OBJECTIVE: To elucidate hormonal disturbances in patients with type 1 diabetes
      mellitus (DM1) with and without growth retardation. METHODS: Patients with DM1
      were divided into two groups, group A consisted of 14 patients with poor growth,
      and group B consisted of 24 patients with normal growth. Serum IGF-I, IGFBP-3,
      basal and stimulated GH, and HbA1c were measured. RESULTS: Serum IGF-I and IGFBP
      3 concentrations were significantly decreased in group A versus both groups B and
      controls in Tanner stages I-III; in addition, these measurements in group B were
      significantly lower compared to controls in Tanner stages II and III, but there
      was no significant difference in prepuberty. Both basal and peak serum GH were
      attenuated significantly in group A versus group B. Basal serum GH in group B
      (normal growth DM1) was significantly elevated versus the controls. There was an
      unambiguous negative linear regression between IGF-I and mean HbA1c in patients
      with DM1. CONCLUSIONS: Growth retardation in patients with DM1 is associated with
      an abnormal GH-IGF-I axis and poor glycemic control.

PMID- 17220060
TI  - Evaluation of glucose intolerance in adolescents relative to adults with type 2
      diabetes mellitus.
AB  - AIM: There is an increasing trend in the prevalence of type 2 diabetes mellitus
      (DM2) in childhood and adolescence, while positive family history of DM2 and
      obesity are the most important risk factors. To study the influence of family
      history and obesity on glucose intolerance in our country was the aim of this
      study. STUDY DESIGN AND METHODS: A total of 105 children and adolescents aged 10
      18 years (mean 13.3 +/- 2.5 years) were included in the study. All children and
      adolescents were divided into three groups according to positive family history
      of DM2 and obesity, and an oral glucose tolerance test (OGTT) was performed for
      all. Prediabetes was defined as impaired glucose tolerance (IGT) and/or impaired
      fasting glucose (IFG). Insulin secretion and insulin resistance were estimated
      using the insulinogenic index; and the homeostatic model assessment for insulin
      resistance (HOMA-IR) and Matsuda index, respectively. RESULTS: The prevalence of
      prediabetes was 15.2% in the whole group, while it was 25.5% in obese children
      who also had a positive family history of DM2. The frequency of hyperinsulinism
      was 57.1% in all groups. Prediabetic children had significant insulin resistance
      (HOMA-IR 11.5 +/- 7.1 and 4.1 +/- 6.4, respectively, p = 0.034). CONCLUSIONS:
      Obesity and glucose intolerance are also a problem in developing countries. The
      risk of prediabetes in children is highest in obese children who also have a
      positive family history of DM2. There is a need for a lifelong preventive program
      starting in childhood to avoid DM2 and decrease cardiovascular risk factors

PMID- 17220061
TI  - Weight evolution in girls treated for idiopathic central precocious puberty with
      GnRH analogues.
AB  - Data concerning the effects of GnRHa on weight gain are scarce. OBJECTIVE: To
      assess the variation of the body mass index (BMI) in girls during GnRHa treatment
      for idiopathic central precocious puberty (CPP). PATIENTS AND METHODS: Semestral
      anthropometric data from 176 girls treated with goserelin or leuprorelin were
      analyzed. RESULTS: BMI z-score increased from 1.5 +/- 0.1 SD before treatment (n
      = 176) to 1.7 +/- 0.2 SD after 24 months (n = 61, p = 0.008). In girls with
      normal weight before treatment, this variation was greater (n = 112, 0.2 +/- 0.1
      SD, p = 0.01) than in those who were overweight (n = 63, -0.9 +/- 0.2 SD, p =
      0.7). In the goserelin group the weight change adjusted for bone age was greater
      (n = 28, 0.4 +/- 0.1 SD) than in the leuprorelin group (n = 5, 0.04 +/- 0.1 SD, p
      = 0.05). CONCLUSIONS: A slight increase in BMI was noted, mainly in girls with
      normal weight before treatment. The influence of different GnRHa on weight must
      be further investigated.

PMID- 17220062
TI  - Chelation therapy and bone metabolism markers in thalassemia major.
AB  - The aim of our study was to investigate the effects of subcutaneous
      desferrioxamine (DFX) and oral deferiprone (L1) therapy on bone metabolism
      markers in patients with thalassemia major. We studied 17 patients with
      thalassemia receiving long-term treatment with desferrioxamine, 20 patients
      receiving long-term treatment with deferiprone, and 15 healthy age-matched
      controls. The following investigations were performed: a) intact parathyroid
      hormone (PTH), 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D
      [1,25(OH)2D] as endocrine parameters; b) alkaline phosphatase (ALP), bone
      alkaline phosphatase (BALP), osteocalcin (OC); c) bone resorption biochemical
      markers in serum and urine pyridinium crosslinks: hydroxylysyl-pyridinoline (HP)
      and lysyl-pyridinoline (LP); d) serum levels of cytokines and growth factors:
      transforming growth factor-beta1 (TGFbeta1), insulin-like growth factor-I (IGF
      I), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-a
      (TNFalpha); e) serum levels of IGF binding protein-3 (IGFBP-3). No significant
      differences among all studied variables were found in patients with thalassemia
      treated with desferrioxamine or deferiprone. In contrast, significant differences
      were found between patients with thalassemia and the control group: intact PTH
      was significantly lower in patients with thalassemia than in the controls (p <
      0.0005), and a significant increase in ALP and BALP (p < 0.0005), but not in OC,
      was found in the patient group. With regard to bone resorption and remodeling
      markers, the urinary excretion of pyridinium crosslinks was higher in patients
      with thalassemia for HP fraction (p < 0.0005) and LP fraction (p = 0.002), as
      well as TGFbeta (p = 0.001). In contrast, IGF-I and IGFBP-3 were reduced when
      compared with controls. In conclusion, the study of bone metabolism markers in
      adult patients with thalassemia reveals a complex behavior with an increase in
      bone resorption indexes. Bone formation did not appear to be impaired. In
      particular, TGFbeta1 was higher in patients with thalassemia receiving L1
      treatment.

PMID- 17220063
TI  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in the
      Irish population.
AB  - OBJECTIVE: To determine the Irish prevalence of autoimmune polyendocrinopathy
      candidiasis-ectodermal dystrophy (APECED), the AIRE mutations involved and
      clinical features of this population. METHODS: All patients were identified
      through paediatricians and endocrinologists in Ireland. Patients were invited to
      attend a multidisciplinary clinic. RESULTS: Thirty-one patients (2-56 years), 18
      female, were identified from 19 families giving an Irish prevalence of 1:130,000.
      Twenty-six patients had hypoparathyroidism, 21 had adrenal insufficiency (AI) and
      10 of 16 had ovarian failure. Three affected patients have died. Many with
      hypoparathyroidism were resistant to 1-alpha-vitamin D. Two needed daily PTH
      injections. Mineralocorticoid deficiency as the first manifestation of AI was
      common. Chronic intra-oral candidiasis affected 25 patients and three had
      leukoplakia. Two had keratoconjuntivitis. Of 22 with AIRE gene analysis, three
      different mutations were identified, one of which is novel. CONCLUSION: APECED is
      rare in Ireland. We saw a significant amount of non-endocrine disease but no
      ectodermal dystrophy. AIRE gene analysis reassured many siblings and identified
      individuals with APECED prior to any symptoms.

PMID- 17220064
TI  - Transient neonatal diabetes mellitus in an infant with paternal uniparental
      disomy of chromosome 6 including heterodisomy for 6q24.
AB  - We describe a female infant who developed transient neonatal diabetes mellitus
      (TNDM) (MIM 601410). At birth she presented with growth retardation and
      macroglossia. Diabetes was diagnosed on the fourth day of life and it resolved
      after two months of insulin therapy. Genetic testing revealed the presence of
      paternal uniparental disomy of chromosome 6 (UPD6) including heterodisomy of
      6q24. This is the first documented case of uniparental heterodisomy for
      chromosome 6.

PMID- 17220065
TI  - Infantile presentation of MODY 3 diabetes.

PMID- 17220066
TI  - Neuroendocrine abnormalities in a neonate with congenital toxoplasmosis.
AB  - The central nervous system is often affected in patients with congenital
      toxoplasmosis. However, hypothalamo-pituitary dysfunction has rarely been
      reported in children with congenital toxoplasmosis, and no case with prolonged
      fever of central origin has been documented so far. We describe a newborn with
      congenital toxoplasmosis who presented with fever due to hypothalamo-pituitary
      dysregulation and combined hypothalamo-pituitary deficiencies consisting of
      central diabetes insipidus, hypothyroidism and ACTH deficiency.

PMID- 17220067
TI  - Osler-Weber-Rendu syndrome as a cause of poor growth during adolescence.
AB  - We report an adolescent boy with poor growth and delayed skeletal age who was
      found to have pulmonary arteriovenous malformations (PAVMs) consistent with
      hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome). While a host
      of chronic diseases, including a number of cardiopulmonary diseases, have
      previously been associated with poor growth or short stature, to our knowledge
      this is the first documented case of PAVM presenting with poor growth,
      manifesting as weight loss and delayed adolescence. This case highlights the
      importance of a thorough physical examination for identifying rare, occult,
      chronic diseases in patients who present with poor growth.

PMID- 17220068
TI  - Klinefelter syndrome presenting with precocious puberty due to a human chorionic
      gonadotropin (hCG)-producing mediastinal germinoma.

PMID- 17220069
TI  - The President's Council on Bioethics: overview and assessment.

PMID- 17220070
TI  - For richer or poorer? Evaluating the President's Council on Bioethics.

PMID- 17220071
TI  - Engineering, gerrymandering and expertise in public bioethics.

PMID- 17220072
TI  - Beyond therapy beyond the beltway: an opening argument for a public debate on
      enhancement biotechnologies.

PMID- 17220073
TI  - Begetting, cloning and being human: two national commission reports against human
      cloning from Italy and the U.S.A.

PMID- 17220074
TI  - Cloning, begetting, and making children.

PMID- 17220075
TI  - Use of a parallel artificial membrane system to evaluate passive absorption and
      elimination in small fish.
AB  - A parallel artificial lipid membrane system was developed to mimic passive mass
      transfer of hydrophobic organic chemicals in fish. In this physical model system,
      a membrane filter-supported lipid bilayer separates two aqueous phases that
      represent the external and internal aqueous environments of fish. To predict
      bioconcentration kinetics in small fish with this system, literature absorption
      and elimination rates were analyzed with an allometric diffusion model to
      quantify the mass transfer resistances in the aqueous and lipid phases of fish.
      The effect of the aqueous phase mass transfer resistance was controlled by
      adjusting stirring intensity to mimic bioconcentration rates in small fish.
      Twenty-three simple aromatic hydrocarbons were chosen as model compounds for
      purposes of evaluation. For most of the selected chemicals, literature
      absorption/elimination rates fall into the range predicted from measured membrane
      permeabilities and elimination rates of the selected chemicals determined by the
      diffusion model system.

PMID- 17220076
TI  - Epifluorescence microscopy and image analysis of high-level polycyclic aromatic
      hydrocarbon contamination in soils.
AB  - Interactions between polycyclic aromatic hydrocarbons (PAHs) and soil are an
      important determinant of their chemical availability and transport. Laboratory
      examination of microscale PAH-soil interaction is limited by the availability of
      methods for particle-scale observation. Inverted epifluorescence microscopy,
      combined with digital photography and computer image analysis, was evaluated for
      specificity and linearity using dissolved PAHs. A pyrene filter (excitation
      wavelength, 360-400 nm; emission wavelength, 450-520 nm) gave nonspecific PAH
      fluorescence, and bias for fluoranthene, benzo[b]fluoranthene,
      benzo[g,h,i]perylene, and benz[a]anthracene was quantified in comparison to that
      for pyrene. Concentrations ranging from 1 to 10 mM for anthracene, fluoranthene,
      and pyrene and from 1 to 50 mM for naphthalene produced a linear response with
      low interpixel variability. Liquid-phase analyses validated use of the technique
      for the descriptive analysis of PAH distribution in solid samples, but liquid
      phase calibration was not quantitative for spiked or field-contaminated soils.
      The mean luminance for three field soils was proportional to the values predicted
      from their chemically measured concentrations and to values from spiked, aged,
      uncontaminated materials. Image analysis of laboratory- and field-contaminated
      samples determined the area distribution of fluorescent intensity and the size of
      fluorescent areas exceeding a threshold luminance. These qualitative descriptions
      of the microscale spatial distribution of PAH contamination are presented as
      potential endpoints for future research on biogeochemical interactions in heavily
      contaminated solids.

PMID- 17220077
TI  - Volatile organic sulfur compounds in anaerobic sludge and sediments:
      biodegradation and toxicity.
AB  - A variety of environmental samples was screened for anaerobic degradation of
      methanethiol, ethanethiol, propanethiol, dimethylsulfide, and dimethyldisulfide.
      All sludge and sediment samples degraded methanethiol, dimethylsulfide, and
      dimethyldisulfide anaerobically. In contrast, ethanethiol and propanethiol were
      not degraded by the samples investigated under any of the conditions tested.
      Methanethiol, dimethylsulfide, and dimethyldisulfide were mainly degraded by
      methanogenic archaea. In the presence of sulfate and the methanogenic inhibitor
      bromoethane sulfonate, degradation of these compounds coupled to sulfate
      reduction occurred as well, but at much lower rates. Besides their
      biodegradability, also the toxicity of methanethiol, ethanethiol, and
      propanethiol to methanogenesis with methanol, acetate, and H2/CO2 as the
      substrates was assessed. The 50% inhibition concentration of methanethiol on the
      methane production from these substrates ranged between 7 and 10 mM. The 50%
      inhibition concentration values of ethanethiol and propanethiol for the
      degradation of methanol and acetate were between 6 and 8 mM, whereas hydrogen
      consumers were less affected by ethanethiol and propanethiol, as indicated by
      their higher 50% inhibition concentration (14 mM). Sulfide inhibited methanethiol
      degradation already at relatively low concentrations: methanethiol degradation
      was almost completely inhibited at an initial sulfide concentration of 8 mM.
      These results define the operational limits of anaerobic technologies for the
      treatment of volatile organic sulfur compounds in sulfide-containing wastewater
      streams.

PMID- 17220078
TI  - Chemical and biological pollution contribute to the immunological profiles of
      free-ranging harbor seals.
AB  - Polychlorinated biphenyls and other persistent organic pollutants have been
      associated with immunotoxicity and outbreaks of (infectious) disease in marine
      mammals by rendering them vulnerable to infection by pathogens such as viruses
      and bacteria. In an immunotoxicological study of free-ranging harbor seals (Phoca
      vitulina), we obtained samples of blood and blubber from seal pups that were live
      captured from two remote and two near-urban sites in British Columbia, Canada,
      and Washington state, USA. Using these samples, we quantified hematology, innate
      immune function, adaptive immune function, and polychlorinated biphenyl
      accumulation. While controlling for confounding factors (age, sex, and
      condition), univariate correlations between phagocytosis (r2 = 0.30, p = 0.002),
      respiratory burst (r2 =0.45, p= 0.000), T-lymphocyte function (r2 = 0.16, p =
      0.028), lymphocyte signaling (r2 = 0.17, p = 0.025), and lymphocyte counts (r2 =
      0.29, p = 0.002), and polychlorinated biphenyl concentrations suggested chemical
      associated immunotoxicity. Principal component analysis of immunological
      endpoints provided additional evidence of immunotoxic effects in seals. However,
      principal component analysis also identified a noncontaminant-related factor by
      distinguishing between seals inhabiting urban versus remote sites, with results
      being consistent with increased pathogen exposure. Elevated fecal coliform
      concentrations in water, and observations of terrestrial spill-over pathogens in
      local seals, further support the notion of biological pollution at these sites.
      Although our study highlights the role that environmental contaminants might play
      in rendering marine mammal populations vulnerable to disease through
      immunotoxicity, it also suggests that biological pollution represents an emerging
      conservation concern.

PMID- 17220079
TI  - Arsenate sorption on two Chinese red soils evaluated with macroscopic
      measurements and extended X-ray absorption fine-structure spectroscopy.
AB  - Arsenic sorption is the primary factor that affects the bioavailability and
      mobility of arsenic in soils. To elucidate the characteristics and mechanisms of
      arsenate, As(V), sorption on soils, a combination of sorption isotherms, zeta
      potential measurements, and extended X-ray absorption fine-structure (EXAFS)
      spectroscopy was used to investigate As(V) sorption on two Chinese red soils.
      Arsenate sorption increased with increasing As(V) concentration and was
      insensitive to ionic strength changes at pH 6.0. Arsenate, mainly as H2AsO4- in
      soil solution at pH 6.0, was strongly sorbed mainly through ligand exchange by
      the two soils. The sorption capacity was affected by the iron and aluminum
      mineral contents in the soils. The zeta potential measurements showed that As(V)
      sorption lowered the zeta potential and the points of zero charge of the soils.
      The EXAFS data indicate that adsorbed As(V) forms inner-sphere complexes with
      bidentate-binuclear configurations, as evidenced by an As-Fe bond distance of
      3.28 +/- 0.04 A and an As-Al bond distance of 3.17 +/- 0.03 A. The two As(V)
      complexes were stable at different As(V) loadings, whereas the proportions were
      related to the aluminum and iron mineral contents in the soils. This study
      illuminated the importance of inclusion of microscopic and macroscopic
      experiments to elucidate sorption behavior and mechanisms.

PMID- 17220080
TI  - Gibbs free energies for dual Langmuir-like adsorption onto hard carbon materials
      in sediment and soils.
AB  - Adsorption of organic compounds onto hard carbon constituents of soils and
      sediments may be described by a dual Langmuir-like equation for adsorption onto
      high-energy sites and low-energy sites. To describe quantitatively the sorbate
      sorbent interactions on these high-energy sites and low-energy sites, Gibbs free
      energies for adsorption onto several soils and sediments were calculated using
      suitable experimental sorption data from the literature. A large part of the
      variation in these Gibbs free energies relative to the pure solid state appeared
      to be related to differences in sorbate molecular symmetry. Generally, for a
      broad range of nonpolar organic compounds, from substituted benzenes to five-ring
      polycyclic aromatic hydrocarbons and hexachlorinated biphenyls, sorbate molecular
      symmetry-corrected Gibbs free energies for high-energy and low-energy adsorption
      relative to the pure solid state were within a narrow range or approximately -23
      and -11 kJ/mol, respectively. These two average values for the geosorbents were
      comparable to corresponding values for adsorption onto activated carbon.

PMID- 17220081
TI  - Modeling biphasic sorption and desorption of hydrophobic organic contaminants in
      sediments.
AB  - A model was developed to predict biphasic sorption and desorption of hydrophobic
      organic compounds in contaminated sediments. The model was based on relatively
      rapid porous diffusion in amorphous organic carbon and slow solid-phase diffusion
      in condensed-phase organic carbon. The model was used to simulate measured solid
      fluid phase desorption (rates and pore-water concentrations) for four polycyclic
      aromatic hydrocarbons exhibiting a range of hydrophobicities (phenanthrene,
      anthracene, pyrene, and benzo[a]pyrene) in two field-contaminated sediments from
      Utica Harbor (Utica, NY, USA) and Rouge River (Detroit, MI, USA). Pore-water
      concentrations have been related to bioavailability, indicating the potential
      usefulness of the model to predict bioavailability. Key model parameters included
      the fraction of condensed-phase carbon (estimated by combustion at 375 degrees
      C), partition coefficient to the condensed-phase carbon (estimated by desorption
      measurements on coal-like particles physically separated from Utica Harbor
      sediments), and diffusivity and ratio of volume to surface area of the condensed
      phase organic matter (fitted to measured desorption data on both sediments and
      for the measured polycyclic aromatic hydrocarbons). Best fit for the diffusion
      coefficient in the condensed-phase organic matter was 8.5 x 10(-20) m2/s, and
      ratio of volume to surface area was 2 microm. These parameters estimated measured
      pore-water concentrations of all polycyclic aromatic hydrocarbons in both
      sediments with an average error of 46% and a correlation coefficient of 0.76 and
      the fast-desorbing fractions (as measured by the fraction removed with a nonpolar
      polymeric sorbent XAD-2) with an average error of approximately 30% and a
      correlation coefficient of 0.54 (14% and 0.76, respectively, for all but
      benzo[a]pyrene). Modeling results were relatively insensitive to the two fitted
      parameters, with changes of an order of magnitude or more being required to
      affect the correlation between the model and observations significantly.

PMID- 17220082
TI  - Activation of the aryl hydrocarbon receptor by carbaryl: Computational evidence
      of the ability of carbaryl to assume a planar conformation.
AB  - It has been accepted that aryl hydrocarbon receptor (AhR) ligands are compounds
      with two or more aromatic rings in a coplanar conformation. Although general
      agreement exists that carbaryl is able to activate the AhR, it has been proposed
      that such activation could occur through alternative pathways without ligand
      binding. This idea was supported by studies showing a planar conformation of
      carbaryl as unlikely. The objective of the present work was to clarify the
      process of AhR activation by carbaryl. In rat H4IIE cells permanently transfected
      with a luciferase gene under the indirect control of AhR, incubation with
      carbaryl led to an increase of luminescence. Ligand binding to the AhR was
      studied by means of a cell-free in vitro system in which the activation of AhR
      can occur only by ligand binding. In this system, exposure to carbaryl also led
      to activation of AhR. These results were similar to those obtained with the AhR
      model ligand beta-naphthoflavone, although this compound exhibited higher potency
      than carbaryl in both assays. By means of computational modeling (molecular
      mechanics and quantum chemical calculations), the structural characteristics and
      electrostatic properties of carbaryl were described in detail, and it was
      observed that the substituent at C-1 and the naphthyl ring were not coplanar.
      Assuming that carbaryl would interact with the AhR through a hydrogen bond, this
      interaction was studied computationally using hydrogen fluoride as a model H-bond
      donor. Under this situation, the stabilization energy of the carbaryl molecule
      would permit it to adopt a planar conformation. These results are in accordance
      with the mechanism traditionally accepted for AhR activation: Binding of ligands
      in a planar conformation.

PMID- 17220083
TI  - Time dependence of phase distribution of pyrethroid insecticides in sediment.
AB  - Synthetic pyrethroids are strongly hydrophobic compounds, and their toxicity in
      sediment is regulated by phase distribution among the sediment, dissolved organic
      matter, and water phases. In the present study, we spiked and equilibrated four
      pyrethroids in two sediments, and we characterized their phase distribution as a
      function of contact time. The freely dissolved concentration measured by solid
      phase microextraction was only a small fraction (<16.3%) of the total pore-water
      concentration as determined by liquid-liquid extraction. The fraction of the
      freely dissolved concentration was significantly greater in the freshwater
      sediment (1.7-16.3%) than in the marine sediment (1.1-4.2%) following 9 d of
      equilibration, and it decreased substantially with contact time to less than 5%
      at 30 d after sediment dosing. Consequently, the apparent organic carbon
      partition coefficient (Koc) and dissolved organic carbon partition coefficient
      (Kdoc) values increased significantly over the contact time, especially in the
      freshwater sediment, suggesting that phase distribution was not at equilibrium
      after 9 d of equilibration. If only the freely dissolved concentration is
      bioavailable, these observations suggest that contact time after sediment dosing
      may greatly affect the bioavailability and, hence, the toxicity of pyrethroids.
      Therefore, a long contact time (> or = 30 d) is recommended for sediment toxicity
      testing of this class of compounds. The dependence of bioavailability on contact
      time also implies that test conditions must be standardized to allow comparison
      between laboratory-dosed samples and field samples.

PMID- 17220084
TI  - Toxicity of four veterinary parasiticides on larvae of the dung beetle Aphodius
      constans in the laboratory.
AB  - The environmental risk assessment of veterinary pharmaceuticals for dung beetles
      is strongly hampered because no standardized test method is available so far.
      Therefore, a test with the temperate dung beetle species Aphodius constans was
      developed. The survival of beetle larvae was determined after exposure to four
      veterinary parasitical pharmaceuticals (ivermectin, moxidectin, dicyclanil, and
      praziquantel) representing different treatment regimes, modes of action, and
      effect levels. The test was performed in the laboratory (three week duration)
      with fresh dung, as well as formulated (dried, ground, and rewetted) dung as test
      substrate (i.e., at least one range-finding test, two definitive test runs per
      pharmaceutical). Ivermectin was the most toxic substance (median lethal
      concentration [LC50] = 0.88-0.98 mg of active substance per kilogram of dung dry
      weight [mg a.s./kg dung (dry wt)] followed by dicyclanil (LC50 = 1.5-6.0 mg
      a.s./kg dung [dry wt]) and moxidectin (LC50 = 4.0-5.4 mg a.s./kg dung [dry wt]),
      whereas praziquantel showed very low toxicity (LC50 > 1,000 mg a.s./kg dung [dry
      wt]). The toxicity in fresh and formulated dung differed by a factor of between
      1.1 and 4. The comparison with literature data on toxic effects of these
      substances on dung beetles in the laboratory or in the field is difficult because
      no results for praziquantel and dicyclanil have been published so far. With the
      use of data from ivermectin and moxidectin, the test results are on the same
      order of magnitude as those known from other studies. On the basis of the
      experiments reported here, it is recommended that this test be standardized in an
      international ring test so that it can be incorporated into the risk assessment
      process as described in the respective international guidelines for the
      registration of veterinary pharmaceuticals.

PMID- 17220085
TI  - Toxicity of six pesticides to common frog (Rana temporaria) tadpoles.
AB  - Amphibian species inhabiting agricultural areas may be exposed to pesticides
      during their aquatic larval phase. We tested the toxicity of six commonly used
      pesticides on Rana temporaria spawn and tadpoles. In acute tests, tadpoles were
      exposed to relatively high concentrations of azoxystrobin, cyanazine,
      esfenvalerate, MCPA ([4-chloro-2-methylphenoxy] acetic acid), permethrin, and
      pirimicarb for 72 h. Chronic exposure tests were performed from fertilization to
      metamorphosis with azoxystrobin, cyanazine, and permethrin at concentrations
      similar to those found in surface waters in agricultural areas in Sweden. The
      most lethal pesticides in the acute exposure were azoxystrobin, permethrin, and
      pirimicarb. Also, negative effects on the growth of the tadpoles were observed
      with azoxystrobin, cyanazine, and permethrin. The chronic exposure at lower
      pesticide concentrations did not result in increased mortality or impaired
      growth. However, we found a positive effect of permethrin on growth and size at
      metamorphosis. The results suggest that the examined pesticides can inflict
      strong negative effects at high concentrations but have no or relatively weak
      effects on R. temporaria spawn or tadpoles at concentrations found in Swedish
      surface waters.

PMID- 17220086
TI  - Cellular physiological effects of the MV Kyowa violet fuel-oil spill on the hard
      coral, Porites lobata.
AB  - The grounding of the Merchant Vessel (MV) Kyowa Violet on a coral reef near Yap,
      Federated States of Micronesia, in December 2002 resulted in the release of an
      estimated 55,000 to 80,000 gallons of intermediate fuel oil grade 180. The
      immediate impact was the widespread coating of mangroves and the intertidal zone
      along more than 8 km of coastline. Of greater concern, however, was the
      partitioning of the fuel oil in the water column, leading to chronic exposure of
      organisms in the ecosystem for a considerable period after the initial event.
      Herein, we report on our examination of one coral species, Porites lobata, nearly
      three months after the initial exposure. We investigated whether changes in
      cellular physiology were consistent with the pathological profile that results
      from the interaction of corals with polycyclic aromatic hydrocarbons, the
      principal constituent of fuel oil. Specifically, we document, to our knowledge
      for the first time, changes in the cellular physiological condition of an exposed
      coral population affected by a fuel-oil spill. We also provide evidence that the
      observed changes are consistent with a recent exposure to fuel oil, as evidenced
      by the presence of characteristic cellular lesions attributed to polycyclic
      aromatic hydrocarbons. Finally, our data support a model for a mechanistic
      relationship between the cellular pathological profile of the coral and a recent
      petroleum exposure, such as the MV Kyowa Violet fuel oil spill.

PMID- 17220087
TI  - Alteration of normal cellular profiles in the Scleractinian coral (Pocillopora
      damicornis) following laboratory exposure to fuel oil.
AB  - Petroleum contamination from oil spills is a continuing threat to our ocean's
      fragile ecosystems. Herein, we explored the effects of the water-soluble fraction
      of crude oil on a stony coral, Pocillopora damicornis (Linneaeus 1758). We
      developed methods for exposing corals to various concentrations of crude oil and
      for assessing the potential molecular responses of the corals. Corals were
      exposed to water-accommodated fraction solutions, and appropriate cellular
      biomarkers were quantified. When compared to the "healthy" control specimens,
      exposed corals exhibited shifts in biomarker concentrations that were indicative
      of a shift from homeostasis. Significant changes were seen in cytochrome P450 1
      class, cytochrome P450 2-class, glutathione-S-transferase-pi, and cnidarian
      multixenobiotic resistance protein- biomarkers, which are involved the cellular
      response to, and manipulation and excretion of, toxic compounds, including
      polycyclic aromatic hydrocarbons. A shift in biomarkers necessary for porphyrin
      production (e.g., protoporphyrinogen oxidase IX and ferrochelatase) and porphyrin
      destruction (e.g., heme oxygenase-1 and invertebrate neuroglobin homologue)
      illustrates only one of the cellular protective mechanisms. The response to
      oxidative stress was evaluated through measurements of copper/zinc superoxide
      dismutase-1 and DNA glycosylase MutY homologue-1 concentrations. Likewise,
      changes in heat shock protein 70 and small heat shock proteins indicated an
      adjustment in the cellular production of proteins. Finally, the results of this
      laboratory study were nearly identical to what we observed previously among
      corals of a different species, Porites lobata, exposed to an oil spill in the
      field after the grounding of the Merchant Vessel Kyowa Violet.

PMID- 17220088
TI  - Plasma membrane surface potential (psiPM) as a determinant of ion
      bioavailability: A critical analysis of new and published toxicological studies
      and a simplified method for the computation of plant psiPM.
AB  - Plasma membranes (PMs) are negatively charged, and this creates a negative PM
      surface electrical potential (psiPM) that is also controlled by the ionic
      composition of the bathing medium. The psiPM controls the distribution of ions
      between the PM surface and the medium so that negative potentials increase the
      surface activity of cations and decrease the surface activity of anions. All
      cations reduce the negativity of psiPM, and these common ions are effective in
      the following order: Al3+ > H+ > Cu2+ > Ca2+ = Mg2+ > Na+ = K+. These ions,
      especially H+, Ca2+, and Mg2+, are known to reduce the uptake and biotic
      effectiveness of cations and to have the opposite effects on anions.
      Toxicologists commonly interpret the interactions between toxic cations (commonly
      metals) and ameliorative cations (commonly H+, Ca2+, and Mg2+) as competitions
      for binding sites at a PM surface ligand. The psiPM is rarely considered in this
      biotic ligand model, which incorporates the free ion activity model. The thesis
      of this article is that psiPM effects are likely to be more important to
      bioavailability than site-specific competition. Furthermore, psiPM effects could
      give the false appearance of competition even when it does not occur. The
      electrostatic approach can account for the bioavailability of anions, whereas the
      biotic ligand model cannot, and it can account for interactions among cations
      when competition does not occur. Finally, a simplified procedure is presented for
      the computation of psiPM for plants, and the possible use of psiPM in a general
      assessment of the bioavailability of ions is considered.

PMID- 17220089
TI  - Assimilation of cadmium in a european lacertid lizard: Is trophic transfer
      important?
AB  - Apart from analyses for elemental contaminants in field-collected specimens, very
      little is known about the assimilation and accumulation of inorganic contaminants
      in reptiles. Recent dietary studies with reptiles (and some other vertebrates and
      invertebrates) have taken care to incorporate the principles of trophic transfer
      by pre-exposing prey items to the elemental contaminant of interest. However,
      there are conflicting data in the literature as to whether biologically
      incorporated metals are more bioavailable to consumers in a food chain than
      simple salts added to the diet, and this study examines this issue in a lacertid
      lizard. Adult individuals of Podarcis carbonelli were exposed to cadmium (Cd) in
      a 21-week dietary study to determine whether the form in which the Cd is provided
      influences assimilation efficiency for this metal. Lizards were provided with Cd
      that had either been biologically incorporated into crickets or as Cd(NO3)2 added
      superficially to crickets just prior to feeding. Radiospectrometric analysis for
      109Cd in animal tissues and fecal material was used to follow Cd accumulation
      over the duration of exposure. The highest levels of accumulation were found
      within the gut. This, combined with the observation of higher rates of
      assimilation over the first five weeks, strongly suggests a rapid accumulation of
      Cd within the gut tissue followed by a slower redistribution to other tissues. No
      statistically different levels of Cd assimilation efficiency were detected
      between the two treatment groups, nor were there any statistically significant
      differences between the two treatment groups in relation to the proportional
      distribution to the gut, liver, or kidneys.

PMID- 17220090
TI  - Utility of in vitro test methods to assess the activity of xenoestrogens in fish.
AB  - The results of the present study have demonstrated the utility of an estrogen
      receptor (ER) competitive ligand-binding assay, a hepatocyte vitellogenin (VTG)
      induction bioassay, and an ER reporter gene bioassay in characterizing the
      activity of model estrogen agonists (17beta-estradiol [E2], ethynylestradiol, and
      nonylphenol) and antagonists (tamoxifen and ZM 189154) in rainbow trout
      (Oncorhynchus mykiss). The in vitro results were validated against in vivo trout
      waterborne exposures to E2 and tamoxifen. The results showed that all three in
      vitro assays were capable of detecting the hormonal activities of the selected
      model compounds in a dose-dependent manner, with the exception of nonylphenol in
      the ER reporter gene bioassay. However, the relative potency rankings of the
      model compounds were not consistent between these assays, which suggests that the
      relative potencies obtained within assays may have limited predictive value
      between assays. Discrepancies in potencies most likely can be attributed to the
      different levels of cellular organization in each assay. In addition to model
      compounds, we also evaluated the responses of the ER-binding assay and the
      hepatocyte VTG induction bioassay to complex mixtures associated with endocrine
      effects in fish, specifically extracts of pulp mill effluent. Of the 14 pulp mill
      effluent extracts tested, only six showed activity in both assays, whereas the
      remaining eight samples showed activity in only one of the two assays. The
      hepatocyte VTG induction bioassay consistently showed that the pulp mill effluent
      extracts were antiestrogenic, which to our knowledge has not been reported in
      previous studies. Collectively, these results suggest that a combination of in
      vitro assays that depend on differing endpoints is required to identify potential
      xenoestrogens and to characterize their modes of action.

PMID- 17220091
TI  - Assessment of inshore/offshore tributyltin pollution gradients in the northwest
      Portugal continental shelf using Nassarius reticulatus as a bioindicator.
AB  - Imposex and organotin tissue contamination were assessed in Nassarius reticulatus
      (L.) populations in the northwest Portuguese continental shelf between 2002 and
      2005 over an area of 735 km2, involving 366 sampling sites. The objective was to
      evaluate the dispersion of tributyltin (TBT) from inshore sources inside the Ria
      de Aveiro estuary into the adjacent deeper sea and to assess endocrine disruption
      in the netted whelk N. reticulatus, using imposex as a biomarker. The highest
      levels of TBT tissue contamination and imposex were found in the whelks inside
      the Ria de Aveiro, and these declined logarithmically with distance from the
      mouth of this estuary. Remarkably, we found that offshore populations were also
      extensively affected: TBT (the dominant organotin) tissue concentration was above
      the detection limits at all sites where whelks were analyzed (12-356 ng TBT-Sn/g
      dry wt), and imposex occurred at 80% of the sampling stations, with relatively
      high values at some sites from the deepest area surveyed. This work shows clearly
      that TBT pollution is not restricted to the Ria de Aveiro but affects a
      significant part of the adjacent continental shelf as well. The ecological
      impacts of TBT pollution on offshore ecosystems are discussed.

PMID- 17220092
TI  - In vitro degradation of hexanitrohexaazaisowurtzitane (CL-20) by cytosolic
      enzymes of Japanese quail and the rabbit.
AB  - Hexanitrohexaazaisowurtzitane (CL-20) is a polycyclic nitramine explosive and
      propellant, currently being considered as a potential replacement for existing
      cyclic nitramine explosives. Earlier studies have provided evidence suggestive of
      adverse liver effects in adult Coturnix spp. exposed to CL-20, yet analysis of
      tissue samples (plasma, liver, brain, heart, or spleen) indicated that CL-20 was
      not detectable in these treated animals. The present study was conducted to
      identify and purify the enzymes capable of CL-20 biotransformation. Results
      indicate that the hepatic biotransformation of CL-20 in vitro was inhibited by
      ethacrynic acid (93%) and by the glutathione (GSH) analogue S-octylglutathione
      (80%), suggesting the involvement of glutathione-S-transferase (GST). Partially
      purified cytosolic alpha- and mu-type GST (requiring presence of GSH as a
      cofactor) from quail and rabbit liver was capable of CL-20 biotransformation. The
      degradation of CL-20 (0.30 +/- 0.05 and 0.40 +/- 0.02 nmol/min/mg protein for
      quail and rabbit, respectively) was accompanied with the formation of nitrite and
      consumption of GSH. Using liquid chromatography/mass spectrometry, we detected
      two intermediates, that is, open-ring, monodenitrated GSH-conjugated CL-20
      biotransformation product with the same deprotonated molecular mass ion at 699
      Da, suggesting isomeric forms of the intermediate metabolites. Identity of the
      conjugated metabolites was confirmed by using ring-labeled [15N]CL-20 and the
      nitro group-labeled [15NO2]CL-20. These data suggest that the in vitro
      biotransformation of CL-20 by GST under the conditions tested may be a key
      initial step in the in vivo degradation of CL-20 in the quail and resulted in the
      formation of more biologically reactive intermediates than the parent compound.
      These data will aid in our understanding of the biotransformation processes of CL
      20 in vivo.

PMID- 17220093
TI  - Physiological modes of action of toxic chemicals in the nematode Acrobeloides
      nanus.
AB  - To gain a better understanding of the mechanisms through which a chemical exerts
      toxicity, a deeper insight is needed regarding the physiological processes that
      take place during a toxic stress. This issue can have important benefits for risk
      assessment, because it can contribute to a better interpretation of toxicity
      data. Here, we study the physiological mode of action of three different
      compounds (cadmium, carbendazim, and pentachlorobenzene) with an experimental
      data-based approach using whole life-cycle toxicity data from the nematode
      Acrobeloides nanus. We use a process-based model, based on the dynamic energy
      budget theory, to study the fluxes of energy related to physiological processes
      and their variation throughout the life cycle. With this approach, we unravel the
      physiological modes of action based on resource allocation, and we model the
      effects of the different modes of action at the population level. The mode of
      action of carbendazim was through a decrease in assimilation, with an additional
      effect on the production of reactive oxygen species (ROS). Cadmium increased the
      costs of growth, with an extra effect on ROS production, and pentachlorobenzene
      decreased assimilation. We compared the present results with those of previous
      studies using the nematode Caenorhabditis elegans, and we found that the modes of
      action for the three compounds differed from those found in A. nanus, showing
      that the life-history characteristics of each organism have a clear influence on
      the resulting modes of action. This highlights the importance of the interactions
      between a chemical and the biological characteristics of the organism in
      determination of the resulting physiological modes of action.

PMID- 17220094
TI  - Toxic effects and oxidative stress in higher plants exposed to polycyclic
      aromatic hydrocarbons and their N-heterocyclic derivatives.
AB  - N-heterocyclic derivatives of polycyclic aromatic hydrocarbons (NPAHs) are
      widespread concomitantly with their parent analogues and have been detected in
      air, water, sediments, and soil. Although they were shown to be highly toxic to
      some organisms, our understanding of their occurrence, environmental fate,
      biological metabolism, and effects is limited. This study evaluated toxic effects
      of three homocyclic aromatic hydrocarbons (PAHs-phenanthrene, anthracene,
      fluorene) and their seven N-heterocyclic derivates on higher terrestrial plants
      Sinapis alba, Triticum aestivum, and Phaseolus vulgaris. Germinability,
      morphological endpoints, parameters of detoxification, and antioxidant components
      of plant metabolism as well as lipid peroxidation were studied in acute
      phytotoxicity tests. Phytotoxicity of NPAHs was generally more pronounced than
      the effects of parent PAHs, and it significantly differed with respect to the
      structure of individual NPAHs. Sinapis alba and T. aestivum were more sensitive
      plant species than P. vulgaris. Chemicals with the strongest inhibition effect on
      germination and growth of plants were phenanthridine, acridine,
      benzo[h]quinoline, and 1,10- and 1,7-phenanthroline. All tested chemicals
      significantly induced activities of detoxification and antioxidant enzymes
      (glutathione reductase, glutathione peroxidase, and glutathione-S-transferase) at
      nanomolar to low micromolar concentrations. Levels of reduced glutathione were
      induced by all tested chemicals except 1,10- and 4,7-phenanthroline. Furthermore,
      fluorene, carbazole, acridine, phenanthrene, phenanthridine, benzo[h]quinoline,
      and 1,7-phenanthroline significantly increased lipid peroxidation. The results of
      our study newly demonstrate significant toxicity of NPAHs to plants and
      demonstrate suitability of multiple biomarker assessment to characterize
      mechanisms of oxidative stress and to serve as an early warning of phytotoxicity
      in vivo.

PMID- 17220095
TI  - Hydrobia ulvae feeding rates: A novel way to assess sediment toxicity.
AB  - Standard acute toxicity tests are widely used to assess contaminated sediments.
      However, such tests last 10 d or more and only provide information regarding
      lethality. Here, we present data concerning the use of a 28-d growth test and a
      24-h test using feeding rate, as measured by egestion rate, of the marine snail
      Hydrobia ulvae. The test was used to assess the toxicity of estuarine sediments
      from a gradient of heavy metal contamination, and its sensitivity and ease of use
      were compared with those of 10-d tests using the amphipod crustacean Corophium
      volutator. Mortality of C. volutator and H. ulvae in 10-d lethal toxicity tests
      showed similar patterns of sensitivity. Lethality tests with both species showed
      no effects when carried out using sediments from a number of sites at which
      ecological impacts are known to occur. By contrast, growth over 28 d in H. ulvae
      was reduced at all sites where other studies have detected adverse ecological
      effects. Feeding rate after 24 h also was decreased at moderately contaminated
      sites where sediments were not acutely toxic, and it was a very good predictor of
      28-d growth (r2 = 0.74). Both tests were straightforward to carry out, so H.
      ulvae has considerable potential as a test organism for chronic toxicity.

PMID- 17220096
TI  - Toxicity and bioaccumulation of 2,4,6-trinitrotoluene in fathead minnow
      (Pimephales promelas).
AB  - Few studies have determined the toxicity and bioaccumulation potential of
      explosive compounds in freshwater fish. In the present study, fathead minnow
      (Pimephales promelas) were exposed to a range of 2,4,6-trinitrotoluene (TNT)
      concentrations (0.44-44 micromol/L [0.1-10 mg/L] and 4.4-22.0 micromol/L [1.0-5.0
      mg/L] in 4- and 10-d experiments, respectively). Median lethal concentrations of
      11.93 micromol/L (2.7 mg/L; 95% confidence limit [CL], 10.29-13.83 micromol/L)
      and 9.68 micromol/L (2.20 mg/L; 95% CL, 9.17-10.22 micromol/L) were calculated in
      the 4- and 10-d experiments, respectively, and median lethal body residue of
      101.0 micromol/kg (95% CL, 86.0-118.7 micromol/kg) was calculated in 4-d
      experiments. To study bioaccumulation, fish were exposed to 4.4 micromol/L (1
      mg/L) of TNT for 12 h. Rapid bioaccumulation of TNT occurred within the first 10
      min of exposure (ku = 30.4 L/kg/ h). Elimination of sigmaTNT (molar sum of TNT
      and degradation products 2- and 4-aminodinitrotoluenes) was fast, with an
      elimination rate (ke) of 2.24/h and a short half-life (0.31 h). The
      bioconcentration factors determined using 6-h mean tissue and water
      concentrations of sigmaTNT were 8.40 and 4.68 L/kg for the uptake experiment and
      the uptake portion of the elimination experiments, respectively. To determine the
      target organ for TNT in fish, juvenile fathead minnow were exposed to 2.2
      micromol/L (0.5 mg/L) of [14C]TNT for 10 d. Radiolabeled compounds primarily
      bioaccumulated in the visceral tissues and spleen in comparison to gill, brain,
      muscle, and remainder tissue groups. The present study demonstrates the low
      bioaccumulation potential and rapid uptake of TNT in the fathead minnow.

PMID- 17220097
TI  - Examining multiple sublethal contaminants on the gray treefrog (Hyla versicolor):
      Effects of an insecticide, herbicide, and fertilizer.
AB  - We examined the single and interactive effects of an insecticide, an herbicide,
      and a fertilizer on gray treefrog (Hyla versicolor) tadpoles. Tadpoles were
      reared in mesocosms from hatching through metamorphosis and were exposed to the
      presence or absence of as many as three contaminants. Tadpoles did not appear to
      be more susceptible to single versus multiple contaminants, which may result from
      positive changes in food resources that compensate for the effects of other
      contaminants.

PMID- 17220098
TI  - Phototoxicity of oil sands-derived polycyclic aromatic compounds to Japanese
      medaka (Oryzias latipes) embryos.
AB  - Alkylated polycyclic aromatic compounds (PACs), which are rich in
      dibenzothiophenes, are present in natural and reclaimed aquatic environments in
      the oil sands region of northern Alberta (Canada). An oil sands-derived PAC
      extract has been shown to induce signs of blue sac disease in Japanese medaka
      (Oryzias latipes) embryos. Information regarding exposure to and effects of oil
      sands PACs is available, but little of this information concerns the impact of
      modifying factors. The present study focuses on the effect of simulated solar
      radiation on oil sands-derived PAC toxicity to Japanese medaka embryos.
      Photomodification of the oil sands PAC extract caused reduced toxicity with an
      increase in the duration of ultraviolet (UV) exposure. Generally, mortality and
      developmental endpoints and, to a lesser extent, growth were affected by
      photomodification. Coexposures of the PAC mixture and UV caused slight increases
      in toxicity for mortality and embryonic developmental endpoints at the longest
      duration of UV exposure tested (16 h). Based on the modest phototoxicity of the
      oil sands PAC extract to Japanese medaka embryos, enhanced toxicity associated
      with UV irradiation may not be a concern for embryos of fish species that are
      common to the oil sands region. However, testing the effects of differing levels
      of UV irradiation on larval fish and invertebrates that may differ in their PAC
      bioaccumulation would improve our understanding concerning the importance of UV
      irradiation as a modifying factor in oil sands environmental risk assessment.

PMID- 17220099
TI  - Aquatic macroinvertebrates in the altes land, an intensely used orchard region in
      Germany: Correlation between community structure and potential for pesticide
      exposure.
AB  - To assess the impact of pesticides on aquatic organisms under realistic worst
      case conditions, a macroinvertebrate community of small ditches was sampled at 40
      sites of the orchard region Altes Land near Hamburg, Germany. To differentiate
      between pesticide impact and other variables, the ditches selected for sampling
      were located at different distances along grassland, unused apple orchards, and
      orchards managed with integrated and/or organic crop protection methods. Samples
      of macroinvertebrates were taken on five dates over two years. In addition to
      biological data, water chemistry and structural parameters were measured. For
      each sampling site, a potential for exposure was calculated on the basis of the
      distance of the ditch to the nearest row of trees and the depth and width of the
      ditch. The neighborhood to either grassland or orchards turned out to have a
      larger impact on the macroinvertebrate community than the potential for exposure.
      Therefore, grassland sites were omitted from further evaluation. Remaining sites
      were grouped into low exposure (sites at unused orchards), medium exposure
      (distance of 3-5 m [track] between trees and ditch), and high exposure (trees
      close to the ditch, mean distance < or = 1.5 m). Principal response curves showed
      differences in community structure between the three exposure groups over time.
      Whereas for sites from the high exposure group significant differences from low
      exposure was observed in all seasons, significant differences between low and
      medium were observed only occasionally. Effects were less pronounced in samples
      taken at springtime before the starting pesticide applications, suggesting some
      community recovery. Species richness was negatively correlated to exposure
      potential. Isopoda, Eulamellibranchiata, and insects, especially Ephemeroptera,
      showed a high negative correlation with the potential for pesticide exposure,
      suggesting that these taxa are sensitive to the pesticide use in the orchards.

PMID- 17220100
TI  - Non-invasive mechanical ventilation: a practice not for all seasons.

PMID- 17220101
TI  - Use of office spirometers in Flemish general practice: results of a telephone
      survey.
AB  - BACKGROUND: While office spirometry is seen as potentially useful and feasible in
      general practice, little is known about its use in Flemish general practice. Our
      aim was to describe the use of spirometers by Flemish GPs, characteristics of
      their spirometry practice, training needs and preferences, and attitudes towards
      office spirometry. METHODS: A telephone survey was set up in a random sample of
      Flemish GPs. Interviews were carried out by a GP researcher using a structured
      piloted questionnaire. RESULTS: 197 out of 243 eligible GPs (81%) were
      interviewed. Most GPs (66%) had never used an office spirometer, 17.3% were using
      one and 16.7% stopped using one. Time constraints (54%) and insufficient
      knowledge and skills (27%) were the main reasons for not using an office
      spirometer (any longer). GPs particularly used their spirometer to diagnose COPD
      and asthma, and less frequently in follow-up. GPs (67.9%), especially current
      users (91.2%), considered spirometry as a GP task. Spirometry training should be
      provided (86%) and spirometry by GPs should be reimbursed (79.5%). More
      information on spirometry would be very useful (62.3%), with a marked preference
      for training in small groups (86.8%). CONCLUSION: Although office spirometry is
      not widespread in Flemish general practice, GPs show an undoubted interest in it.
      They need educational and financial support to overcome prevailing barriers in
      establishing office spirometry on a routine basis.

PMID- 17220102
TI  - Exacerbations and associated healthcare cost in patients with COPD in general
      practice.
AB  - BACKGROUND: Acute exacerbations are a characteristic clinical expression of
      chronic obstructive pulmonary disease (COPD). The objective of this study was to
      investigate the occurrence rate, management, and healthcare costs of
      exacerbations in patients with COPD in Dutch general practice. METHODS: Baseline
      data set from the COPD on Primary Care Treatment (COOPT) trial was used. Details
      on the occurrence and management of exacerbations were collected by systematic
      medical record review for the 2-year period preceding trial inclusion. RESULTS:
      The mean age of the 286 study subjects involved was 59.2 (SD 9.6) years,
      postbronchodilator FEV1 67.1% (SD 16.2) of predicted. Following ERS criteria,
      subjects suffered from: no (26%); mild (19%); moderate (40%); or severe (15%)
      airflow obstruction. The overall mean and median annual exacerbation rates were
      0.88 (SD 0.79) and 0.5 (IQR 1.0), respectively. Exacerbation rate was not related
      to severity of airflow obstruction (p=0.628). Mean annual exacerbation costs per
      subject were 40 Euro, 53 Euro, 61 Euro and 92 Euro for the respective severity
      subgroups (p=0.012). The increase of costs in the more severe subgroups was
      mainly attributable to more physician consultations, diagnostic procedures, and
      prescription of reliever medication (e.g., bronchodilators, cough preparations).
      CONCLUSIONS: Occurrence of exacerbations did not depend on the severity of
      airflow obstruction, whereas the healthcare cost associated with exacerbations
      increased along with the severity of the disease.

PMID- 17220103
TI  - Clearance of technetium-99m-DTPA in pulmonary sarcoidosis.
AB  - BACKGROUND: The aim of this study was to explore the possible association of the
      lung clearance of 99mTc-DTPA scan with HRCT lung abnormalities and with the
      pulmonary function tests [PFTs] in patients with sarcoidosis. METHODS: We studied
      prospectively 15 patients [5 males, 10 females] of median age 46yr [range 27-67]
      with histologically proved sarcoidosis. HRCT scoring included the sum of the
      severity and extent of lymph node enlargement and parenchymal involvement.
      RESULTS: The mean DTPA clearance half-time [tau 1/ <40 min] was found [mean [SD]]
      38.3+/-4.5min. The lymph node enlargement was found 34% and the parenchymal
      involvement 12%. DTPA clearance was negatively correlated with the parenchymal
      involvement [r= -0.651, p=0.0091]. The HRCT parenchymal abnormalities were found
      significantly correlated with PFTs [FVC [r= -0.65, p=0.008] and TLCO [r= -0.76,
      p=0.02]. CONCLUSIONS: Our data suggest a moderate association between 99mTc-DTPA
      scan and HRCT in pulmonary sarcoidosis. However, further studies in large scale
      of sarcoid patients are needed to clarify the role of this novel methodology in
      the evaluation and follow-up of this disorder.

PMID- 17220104
TI  - Staff training influence on non-invasive ventilation outcome for acute
      hypercapnic respiratory failure.
AB  - BACKGROUND: Although non-invasive ventilation (NIV) efficacy in the treatment of
      acute hypercapnic respiratory failure (AHRF) have been previously demonstrated,
      not all the studies reveal this fact in the same degree, with some variability in
      the results. This study aimed to analyse variables related to NIV outcome for
      AHRF. METHODS: A group of consecutive patients requiring NIV due to AHRF were
      included in a prospective observational cohort study performed in conventional
      wards. Variables considered included those reported in the literature, as well as
      staff problems during the management of the ventilators. The study aimed to
      include all patients during one year, but after the initial results, it had to be
      suspended. RESULTS: Fifteen patients were included in the study: 10 males, mean
      age 68+/-12. APACHE-II score was 17.6+/-6.5. pH and pCO2 before NIV were 7.22+/
      0.11 and 110+/-72 mmHg respectively. pH, corticosteroids use, APACHE score, and
      EPAP were found to influence outcome. Besides, an inadequate use of NIV due to
      lack of personnel training was detected in all patients with NIV failure (RR 3.5;
      95% CI: 1.08-11.2; p = 0.007). In the light of these results, the study had to be
      suspended and patients were transferred to the respiratory ward. CONCLUSIONS: NIV
      is a life-saving respiratory treatment influenced by several factors, of which
      staff training is a key one. Centres attending acute respiratory patients should
      have an area in which this requirement is fulfilled.

PMID- 17220105
TI  - Why act early in COPD?

PMID- 17220106
TI  - Smoking habits among the hospital staff of a General Hospital in northern Greece:
      a long way for smoke-free hospitals.
AB  - BACKGROUND AND AIM: The aim of the study was to evaluate the smoking habits of
      all staff working in a General Hospital, and to examine whether these habits
      comply with the introduction of a tobacco law in July 2002, where smoking in
      enclosed public areas, including hospital buildings, has been forbidden in
      Greece. METHODS: All hospital staff in Serres General Hospital was asked to
      complete and return a questionnaire about their smoking habits. The questionnaire
      was voluntary and anonymous. The survey was conducted from October 2003 to
      January 2004. RESULTS: Six hundred and twenty three (74%) of the 847 members of
      staff responded; 310 (50%) were current smokers and 313 (50%) were non-smokers of
      whom 101 (32%) were ex-smokers. The prevalence of current smokers was the highest
      among nurses (57%) and the lowest among doctors (31%). Male smokers (42%) were
      outnumbered by female smokers (54%) in all age groups up to the age of 60 years
      (p<0,01), although the reverse is the trend in Greek population (47% and 29%,
      respectively). The highest rate of smokers was found at the age group of 31-40
      years (60%), while these above sixty years had the smallest (29%). Seventy
      percent of current smokers had at least one family member who was current smoker
      vs 49% of non-smokers (p<0,001). The vast majority of smokers (94%) continued to
      smoke in hospital, of whom 62% smoke more than 5 cigarettes while at work.
      CONCLUSIONS: The high rate of smokers among the health professionals compared to
      those in the general population would probably have a negative influence on the
      development, implementation and inspection of workplace smoking bans in Greece.
      Increased efforts to promote tobacco education and intervention among doctors and
      nurses and to establish specialist smoking cessation services throughout the
      National Health Service should be the standard component of antismoking policy
      for the law to be effective.

PMID- 17220107
TI  - Pedunculated solitary fibrous tumours arising from the pleura.
AB  - Solitary fibrous tumour (SFT) is one of the rare tumours which arise from
      visceral pleura. Klemperer and Rabin first described SFT as a distinct clinical
      entity among primary pleural tumoUrs in 1931. Approximately 820 cases have been
      reported in literature to date. The management of patients with SFT is complete
      resection of the tumour and follow up of the patient to detect any possible late
      recurrence. In the present paper, we report two cases of pedunculated solitary
      fibrous tumours of the pleura that appeared as a wandering chest nodule to which
      surgical resection undertaken at our hospital. The aim is to summarise our
      experience in the management of solitary fibrous tumour.

PMID- 17220108
TI  - Primary alveolar hypoventilation and XXXXY chromosopathy.
AB  - The association of primary alveolar hypoventilation (PAH) and chromosomic
      diseases has not been described previously. A 19 year-old man with Fraccaro's
      syndrome (XXXXY karyotype) was admitted to evaluate chronic hypercapnic
      respiratory failure, pulmonary arterial hypertension and cor pulmonale. PAH was
      diagnosed. As effective treatment, such as non-invasive positive pressure
      ventilation (NIPPV), is available for this disorder we should intensify the
      search for PAH in patients with chromosome disease.

PMID- 17220109
TI  - Hemomediastinum and bilateral hemothorax with extensive angiomatosis of anterior
      mediastinum.
AB  - Angiomatosis is a rare, benign but clinically extensive and serious vascular
      lesion of soft tissue. Hereby, we report a case of diffuse angiomatosis of
      mediastinum, presenting with hemomediastinum and bilateral massive hemothorax in
      a 19-year old boy. On medical imaging, mediastinal widening along with enhanced
      small vessels and capillaries were detected. On operation, hemorrhagic sponge
      like vascular tissue patches were seen extensively in pericardium, pleura, lymph
      node and thymus as well. The lesion was debulked. The pathologic evaluation
      revealed characteristic features of soft tissue angiomatosis involving thymus,
      lymph node, pleura, pericardium and its fibrofatty tissue. Diffuse angiomatosis
      should be considered for differential diagnosis of vascular lesions of anterior
      mediastinum.

PMID- 17220110
TI  - What does it mean to be relational? A framework for assessment and practice.
AB  - The authors begin with a question regarding how to better draw upon relational
      thinking in making case assessments and treatment plans. They first address
      issues regarding the cultural construction of self and relationships, integrating
      women's psychology, family systems, and collectivist culture literatures within a
      discussion of power. Then they present a heuristic framework for how individuals
      orient themselves within relationships that includes two dimensions--focus and
      power--and evolves out of the social context. From these two dimensions, a
      typology of four basic relational orientations is presented: position directed,
      rule directed, independence directed, and relationship directed. Case examples
      from couple's therapy and suggestions for practice are provided.

PMID- 17220111
TI  - Negotiated nonmonogamy and male couples.
AB  - One issue that has the potential to confound family or couples therapists working
      with male couples is the issue of nonmonogamy. For many therapists, sexual
      nonexclusivity challenges fundamental clinical assumptions that "affairs," or
      extra-relationship sex or romantic involvements, are symptoms of troubled
      relationships and are always a form of "sexual acting out." This article explores
      the issue of sexual exclusivity and nonexclusivity within male couples. In order
      to achieve both clinical and cultural competency in work with male couples,
      therapists need to challenge their cultural biases regarding monogamy.

PMID- 17220112
TI  - I. Genotype-environment interaction in the schizophrenia spectrum: genetic
      liability and global family ratings in the Finnish Adoption Study.
AB  - In the Finnish Adoption Study, a national sample of adoptees with high versus low
      genetic liability for schizophrenia spectrum disorders was indexed by DSM-III-R
      diagnoses of their biological, adopting-away mothers. The rearing-family
      environments of the adoptees were independently evaluated from global ratings of
      directly observed adoptive family relationships. The interaction of high genetic
      liability and dysfunction of the rearing families predicted highly significantly
      to schizophrenia spectrum disorder of the adoptees at 21-year follow-up. Either
      low genetic liability or healthy rearing protected against a spectrum outcomes
      for the adoptees. Initial adoptive parent diagnosis, as a proxy for rearing
      family dysfunction, predicted to adoptee outcome only as a trend.

PMID- 17220113
TI  - II. Genotype-environment interaction in the schizophrenia spectrum: qualitative
      observations.
AB  - Previous reports from the Finnish Adoptive Family Study of Schizophrenia have
      documented significant interplay between genetics (G) and family rearing (E),
      leading to adoptee outcomes of schizophrenia spectrum disorders. Quantitative
      evidence for this interplay is significantly enhanced when both high genetic
      liability and severe environmental dysfunction are present. However, when either
      genetic liability is low or the rearing environment is healthy, the adoptees
      appear to be resiliently protected against a pathologic outcome. Nevertheless,
      exceptions to this pattern do occur. Six qualitative vignettes, together with
      quantitative measures and categorical diagnoses from the same families,
      illustrate how multiple methods partially confirm one another and also suggest
      where further exploration of gene-environment interaction is needed.

PMID- 17220114
TI  - Processes linked to contact changes in adoptive kinship networks.
AB  - The purpose of this study was to reveal underlying processes in adoptive kinship
      networks that experienced increases or decreases in levels of openness during the
      child's adolescent years. Intensive case study analyses were conducted for 8
      adoptive kinship networks (each including an adoptive mother, adoptive father,
      adopted adolescent, and birth mother), half of whom had experienced an increase
      in openness from indirect (mediated) to direct (fully disclosed) contact and half
      of whom had ceased indirect contact between Waves 1 and 2 of a longitudinal
      study. Adoptive mothers tended to be more involved in contact with the birth
      mother than were adoptive fathers or adopted adolescents. Members of adoptive
      kinship networks in which a decrease in level of contact took place had
      incongruent perspectives about who initiated the stop in contact and why the stop
      took place. Birth mothers were less satisfied with their degree of contact than
      were adoptive parents. Adults' satisfaction with contact was related to feelings
      of control over type and amount of interactions and permeability of family
      boundaries. In all adoptive kinship networks, responsibility for contact had
      shifted toward the adopted adolescent regardless of whether the adolescent was
      aware of this change in responsibility.

PMID- 17220115
TI  - To rebuild lives: a longitudinal study of the influences of the Holocaust on
      relationships among three generations of women in one family.
AB  - The current article presents an analysis of the life stories of three generations
      of women within a family headed by a Holocaust survivor. Its uniqueness lies in
      its double analysis of the stories told by these women, with an interval of 12
      years between telling. The first series of interviews were conducted in the early
      1990s within the framework of a pioneering study in which, for the first time,
      three generations in each of 20 families were interviewed and their narratives
      analyzed. The current analyses are based on the perspective that, through life
      narratives, it is possible to view the transformations of relationships over time
      and that these transformations in relationships are central to personal
      development. We will examine the relationships of the women in these three
      generations, both with significant others and with each other. We will trace
      processes of development and changes in these relationships over the 12 years.
      Finally, we will discuss the social and methodological implications of our study.

PMID- 17220116
TI  - Play with me at my speed: describing differences in the tempo of parent-infant
      interactions in the Lausanne Triadic Play paradigm in two cultures.
AB  - The goal of the present study was to examine the tempo of triadic play in Swedish
      and American families through a comparison of 20 families from each culture. When
      infants were approximately 3 months old, families in both cultures participated
      in the Lausanne Triadic Play (LTP), a paradigm that facilitates the examination
      of the triad as a whole and an organization of its parts. All family play
      sessions were coded separately in Sweden and America using coding systems that
      had been developed in each country. Dynamics within the triadic play were
      compared across cultures, and also across coding systems. Results indicated that
      both coding systems described a distinct difference in the tempo of play between
      American and Swedish Families. Overall, although there were many similarities
      between countries, American families were found to have a faster pace in triadic
      play than Swedish families. This difference in tempo is explored in the data
      analyses and the discussion of this article.

PMID- 17220118
TI  - Vamping on ultrafractal.

PMID- 17220117
TI  - Can spouses provide knowledge of each other's communication patterns? A study of
      self-reports, spouses' reports, and observational coding.
AB  - The purposes of this study were (1) to assess individuals' self-reports of
      communication and their reports about their spouses' communication in order to
      examine the congruence of spousal views and (2) to investigate whether each
      report provided unique information about observed marital interactions. These
      associations were evaluated in a sample of 119 longtime married couples. The
      Verbal Aggression and Cooperation subscales from the Conflicts and Problem
      Solving Scales were used as measures of negative and positive aspects of
      communication. The findings indicated that self-reports of both verbal aggression
      and cooperation were strongly associated with the same individual's report of his
      or her spouse's verbal aggression and cooperation. Conversely, self-reports were
      only moderately associated with reports made by spouses (e.g., the husband's
      report of his wife's communication). Hence, within-reporter agreement was higher
      than between-reporter agreement about marital communication. When entered into
      regression models, reports made by spouses, but not self-reports, explained
      unique variance in observations of marital hostility and affection. There was one
      exception: Wife self-report of verbal aggression explained unique variance in
      coders' ratings of wife hostility, controlling for husband report of wife verbal
      aggression. Findings indicate the importance of assessing partners' views of one
      another's communication for the most accurate portrayal of marital interactions.
      Implications for research and clinical work are discussed.

PMID- 17220119
TI  - FieldVis: a tool for visualizing astrophysical magnetohydrodynamic flow.

PMID- 17220120
TI  - Physically based sound synthesis for large-scale virtual environments.

PMID- 17220121
TI  - Dynamic sharing of large-scale visualization.

PMID- 17220122
TI  - Sketch-based interaction.

PMID- 17220123
TI  - Sketch interpretation using multiscale models of temporal patterns.

PMID- 17220124
TI  - Advances in mathematical sketching: moving toward the paradigm's full potential.

PMID- 17220125
TI  - Free-form sketching of self-occluding objects.

PMID- 17220126
TI  - Sketch-based 3D-shape creation for industrial styling design.

PMID- 17220127
TI  - A sketch-based interface for clothing virtual characters.

PMID- 17220128
TI  - Using a GPU to accelerate die and mold fabrication.

PMID- 17220129
TI  - The digital chameleon principle: computing invisibility by rendering
      transparency.

PMID- 17220130
TI  - How to solve a cubic equation, part 4: the 111 case.

PMID- 17220131
TI  - Electrocardiology of atrial fibrillation. Current knowledge and future
      challenges.

PMID- 17220132
TI  - Atrial fibrillation and waveform characterization. A time domain perspective in
      the surface ECG.

PMID- 17220133
TI  - Detection and feature extraction of atrial tachyarrhythmias. A three stage method
      of time-frequency analysis.

PMID- 17220134
TI  - Processing of intracardiac electrograms in atrial fibrillation. Diagnosis of
      electropathological substrate of AF.

PMID- 17220135
TI  - Management of atrial tachyarrhythmias. Rhythm control using implantable devices.
AB  - Presently, most devices with atrial diagnostic and therapeutic features are
      implanted in patients for electrical treatment of bradyarrhythmias and
      ventricular tachyarrhythmias. The painless electrical strategies for prevention
      and termination of ATa have not demonstrated significant clinical effectiveness
      in the general population with ATa. The effectiveness of ATP in reducing burden
      may be significantly higher in a subgroup of patients with a high incidence of
      stable ATa, but this needs to be evaluated prospectively. Smart sensing and
      detection schemes will also help provide accurate information and determine when
      ATa can be terminated with ATP. Although electrical defibrillation is effective,
      the discomfort associated with atrial shocks has limited the widespread use of
      this technology. Recent technological advances have increased the capabilities of
      implantable devices to store large amounts of diagnostic information. In the near
      future, implantable devices without transvenous leads may be implanted to monitor
      a variety of physiologic signals. This could help improve clinical outcomes and
      determine which therapies (pharmacologic, ablative, or electrical) would be most
      effective as well as monitor their safety and efficacy. Frequent monitoring from
      home and the availability of this data to the physician/nurse on the Internet can
      potentially improve the management of patients' ATa at a much lower cost.

PMID- 17220136
TI  - Linear and nonlinear coupling between atrial signals. Three methods for the
      analysis of the relationships among atrial electrical activities in different
      sites.

PMID- 17220137
TI  - Descriptors of wavefront propagation. Endocardial mapping of atrial fibrillation
      with basket catheter.

PMID- 17220138
TI  - Analysis of electrocardiograms during atrial fibrillation. A biophysical model
      approach.

PMID- 17220139
TI  - Design projects.

PMID- 17220140
TI  - The first experiments on electrical safety.

PMID- 17220141
TI  - Vacation: all I ever wanted.

PMID- 17220142
TI  - Sex and stem cell research.

PMID- 17220143
TI  - Expressions of vascular endothelial growth factor and CD34 in oral aphthous
      lesions of Behcet's disease.
AB  - OBJECTIVE: Behcet's disease (BD) is an immunoin-flammatory vasculitis with an
      unknown etiopathogenesis. Vascular endothelial growth factor (VEGF) is a cytokine
      stimulating angiogenesis. It has been suggested to play a role in inflammation
      and pathogenesis of vasculitic processes. STUDY DESIGN: VEGF and CD34 expressions
      were assessed in samples taken from oral aphthous lesions. The patients were
      evaluated for disease activity, duration of lesions, serum C-reactive protein
      (CRP) levels and erythrocyte sedimentation rate (ESR). RESULTS: Twenty-six
      patients were included. Fourteen (53.9%) had increased CRP levels and 12 (46.1%)
      had increased ESR levels. Positive VEGF and CD34 staining were detected in 46.2%
      and 69.2% of biopsy samples, respectively. There was good positive correlation
      between them. The frequency of positive VEGF and CD34 staining was statistically
      higher in lesions with a duration of more than 6 days. No correlation was found
      between positive VEGF staining and serum CRP level, ESR and disease activity.
      CONCLUSION: Increased VEGF expression in correlation with CD34 positivity in oral
      aphthous lesions may show the role of VEGF in pathogenesis of these vasculitic
      lesions. We have concluded that VEGF may play a role during the course of oral
      aphthous lesions in BD.

PMID- 17220144
TI  - Automatic image segmentation with linear clustering for quantification of
      neointimal formation after surgical vein grafting.
AB  - OBJECTIVE: To identify extracellular matrix deposition on combined Masson elastin
      stains from cross-sectional, fixed vein grafts. STUDY DESIGN: Source vectors from
      RGB components of color images are transformed into new vectors with most of the
      energy concentrated in fewer coefficients based on the eigenvalues and
      eigenvectors of their co-variance matrix so their dimension can be reduced for
      efficient computation and analysis. The vectors are distributed in a triangular
      shape in which most vectors are located in a long, narrow strip that can be
      approximated by a straight line while a separate group of vectors from collagen
      areas form a loose cluster away from the line. An iterative procedure has been
      developed for the representative vectors in the 2 centroids for linear and
      circular clusters. The linear centroid consists of all vectors in a straight
      line, and the centroid of the circular cluster is a single vector. Vector
      classification is based on the measure of its distance to each of the 2
      centroids. RESULTS: The automatic segmentation of the collagen content pixels in
      green-blue matches the image background color. CONCLUSION: The procedure
      automatically quantifies and characterizes the neointimal deposition after
      surgical vein grafting in mice.

PMID- 17220145
TI  - Flow cytometry and spectral imaging multiphoton microscopy analysis of CD36
      expression with quantum dots 605 of untreated and 7-ketocholesterol-treated human
      monocytic cells.
AB  - OBJECTIVE: To evaluate CD36 expression with quantum dots 605 (QDs 605) on
      untreated and 7-ketocholesterol (7KC)-treated monocytic U937 cells by flow
      cytometry (FCM) and confocal and multiphoton laser scanning microscopy (CLSM).
      STUDY DESIGN: Cells were analyzed by CLSM, following flow cytometric
      quantification of CD36 expression and 7KC uptake. Image sequences were obtained
      by spectral analysis in monophoton and multiphoton CLSM and analyzed by the
      factor analysis of medical image sequences (FAMIS) algorithm to differentiate
      emission spectra. In CLSM analysis, cell deposits were screened in ultraviolet
      excitation modes to optimize the possibilities of QDs 605 and have the benefit of
      nuclei counterstaining by DAPI. RESULTS: FCM and CLSM reveal the expression of
      CD36 by means of QDs 605. FCM provides information on 7KC uptake. CLSM provides
      the localization of 7KC vs. DAPI. As factor curves and images show the red,
      narrow emission of QDs 605 vs. violet and blue emissions of 7KC and DAPI,
      respectively, a reliable identification of CD36 is obtained. CONCLUSION: QDs 605
      are useful tools to perform antigenic expression in FCM and CLSM. Moreover, CLSM
      and subsequent spectral analysis provide a more specific characterization of QDs
      605 fluorescent emission in the UV excitation mode and a simultaneous
      identification of 7KC.

PMID- 17220146
TI  - Clinical value of cell counts and indices in testicular fine needle aspiration
      cytology in primary infertility: diagnostic performance compared with histology.
AB  - OBJECTIVE: To compare the diagnostic value of testicular fine needle aspiration
      (FNA) cytology with that of open biopsy in primary infertility and nonobstructive
      azospermia or severe oligozoospermia, to evaluate the reliability of percentage
      cell counts and cell indices. STUDY DESIGN: Thirty patients (21 azospermic and 9
      severe oligozoospermic) who had samples for testicular FNA obtained from both
      testis (mean age = 28.7) and open biopsy were included in the prospective study.
      Primary infertility, history, complete physical examination, hormonal assay and
      testicular ultrasound data were evaluated. One case was excluded because of an
      unsatisfactory result in aspiration cytology. The percentage population of
      Sertoli cells and spermatogenetic cells, in addition to spermatic index, sertoli
      cell index and sperm-Sertoli cell indexes, was calculated. The statistical
      analysis was determined using the paired t test. RESULTS: Progressively
      increasing values of the Sertoli cell index and progressively decreasing values
      of the sperm--Sertoli cell index were seen in maturation arrest,
      hypospermatogenesis and Sertoli cell-only syndrome. The difference between mean
      counts and indices in normal spermatogenesis and other histologic categories was
      statistically significant (p < 0.05). CONCLUSION: Percentage cell counts and cell
      indices in testicular FNA significantly correlate with histological categories.
      In primary male infertility, testicular FNA can be performed instead of open
      biopsy.

PMID- 17220147
TI  - "Field cancerization" in the urothelium of the bladder.

PMID- 17220148
TI  - Urothelial changes induced by therapeutic procedures for bladder cancer.

PMID- 17220149
TI  - Noninvasive urothelial neoplasms: which classification?

PMID- 17220150
TI  - Difference between mean and threshold as a measure of intensity in confocal
      microscopy images.

PMID- 17220151
TI  - Utility of prostate biopsy morphometric sum optical density for identifying
      extraprostatic extension on subsequent prostatectomy.

PMID- 17220152
TI  - Sampling of sentinel nodes: a simulation study.

PMID- 17220153
TI  - An interview with Donald Berwick. Interview by Paul M Schyve.

PMID- 17220154
TI  - An interview with Jerry Gurwitz. Interview by David Bates.

PMID- 17220155
TI  - Promoting collaboration and transparency in patient safety.
AB  - BACKGROUND: The Minnesota Alliance for Patient Safety (MAPS) collaborative was
      founded in 2000 by the Minnesota Hospital Association (MHA), the Minnesota
      Medical Association, and the Minnesota Department of Health. CREATING A CULTURE
      OF LEARNING, JUSTICE, AND ACCOUNTABILITY: MAPS made it a priority to make the
      health care workplace one that encourages learning from adverse events. MAPS is
      pioneering a statewide model of a "just" culture--one that supports learning yet
      holds individuals accountable for errors. LEGISLATIVE CHANGES: In 2001, MAPS
      helped revise the Minnesota peer review law to allow hospitals to share key
      safety information through electronic databases such as the MHA Patient Safety
      Registry. The revisions paved the way for the 2003 landmark Minnesota Adverse
      Health Care Event Reporting Act, which encourages reporting of root cause
      investigations and steps taken by facilities to prevent recurrence. In 2003 the
      Patient Safety Registry, an electronic database, was expanded to serve as a
      confidential clearinghouse for facilities' reporting of adverse events. PATIENT
      SAFETY TOPICS: MAPS serves as catalyst for developing and disseminating best
      practices on topics such as health literacy, falls prevention, culture of safety,
      engaging patients, and consumers' medication tracking. CONCLUSION: The six-year
      collaborative effort by the many organizations comprising MAPS has led to a
      transformation in Minnesota's health care safety culture.

PMID- 17220156
TI  - Translating patient safety legislation into health care practice.
AB  - BACKGROUND: An independent state agency, the Authority is charged with taking
      steps to reduce and eliminate medical errors by identifying problems and
      recommending solutions that promote patient safety. PENNSYLVANIA PATIENT SAFETY
      REPORTING SYSTEM (PA-PSRS): The Authority implemented PA-PSRS, a mandatory
      reporting and analysis system for both adverse events and near-misses, among 450
      hospitals, birthing centers, and ambulatory surgical facilities. Pennsylvania is
      the only state to require the reporting of both adverse events and near-misses.
      THE PATIENT SAFETY ADVISORY: The Patient Safety Advisory is a quarterly
      publication containing articles about trends in reports submitted to PA-PSRS. The
      peer-reviewed articles include analysis of and lessons learned from PA-PSRS
      reports and evidence-based risk reduction strategies based on research in the
      clinical literature. To complement and reinforce the effectiveness of certain
      Advisory articles, the Authority has introduced electronic, educational tool kits
      on its Web site that can be downloaded. They include posters, draft policies,
      audio-slide presentations for staff training, and other materials related to
      clinical implementation of patient safety interventions and protocols. SUMMARY
      AND CONCLUSION: In just over two years, the Authority has developed a program
      that turns reports into actionable items through the analysis and research of
      adverse events and near-misses.

PMID- 17220157
TI  - A cooperative approach to standardizing care for patients with AMI or heart
      failure.
AB  - BACKGROUND: In fall 2003 the five hospitals in Wichita, Kansas, formed a
      collaborative to improve care for patients presenting with acute myocardial
      infarction or heart failure (HF). Standard order sets were developed from
      guidelines developed by the American College of Cardiology and the American Heart
      Association. THE WICHITA CITYWIDE HEART CARE COLLABORATIVE GETS TO WORK: The
      order sets, which highlighted the appropriate interventions and made their
      implementation a "checkbox" activity, were placed in the progress note section of
      the medical record. Booklets for patient education on heart care were developed.
      RESULTS: All five hospitals have experienced significant improvement in core
      measure data. For example, for angiotension-converting enzyme inhibitor for left
      ventricular systolic dysfunction, the overall compliance score improved from 70%
      to 85%, a 15% improvement in 18 months. Compliance for HF was perhaps more
      successful, given the low level of initial compliance (50%). DISCUSSION:
      Physician compliance was enhanced by incorporating the guidelines into
      practitioners' daily workflow needs, providing prompt feedback on their
      performance, incorporating their suggestions made at the point of care, and using
      process measurements.

PMID- 17220158
TI  - Evaluating sample medications in primary care: a practice-based research network
      study.
AB  - BACKGROUND: No reports have objectively evaluated safety of samples in primary
      care practices. A study was conducted to determine adherence to the Institute for
      Safe Medication Practices (ISMP) recommendations for safe distribution of
      medication samples to minimize medication errors. METHODS: In 2004, 17 urban and
      rural primary care practices participated in a two-phase observational study: (1)
      a site visit to collect inventory data and perform assessment of medication
      sample dispensing procedures and (2) a survey questionnaire for providers and
      patients upon sample medication provision. RESULTS: No practices were compliant
      with all seven ISMP recommendations. Twelve of 17 practices had policies for
      sample medication dispensing, and 7 had policies for labeling. Sample medication
      use was evaluated for 585 office visits and 27 patient surveys. Fifty-eight
      sample medications were dispensed during 55 of 585 patient visits. Common reasons
      for using sample medications included availability and need for a short-term
      trial for a chronic medication. Verbal communication only was provided most of
      the time for patient education regarding appropriate sample medication use and
      side effects. DISCUSSION: Primary care practices in this research network did not
      follow safe and appropriate sample medication dispensing procedures as outlined
      by ISMP. Both labeling and patient instructions were inadequate and may increase
      the risk for medication errors.

PMID- 17220159
TI  - Prioritizing patient safety interventions in small and rural hospitals.
AB  - BACKGROUND: A study was conducted in 2004 to determine if 26 interventions-
      distributed among nine patient safety areas and as recommended by an expert panel
      as relevant to rural hospitals--would be validated in terms of relevance and
      implementability for small and rural facilities. METHODS: The chief executive
      officers (CEOs) and/or key managers responsible for patient safety activities in
      a diverse group of 29 small and rural hospitals assessed the potential
      effectiveness and feasibility of the 26 interventions. Representatives of 25
      hospitals participated in structured, follow-up phone discussions. RESULTS:
      Adverse drug events were the highest-priority area for 14 hospitals, followed by
      patient falls (selected by 5 hospitals). Some hospitals had already implemented
      intervention 1 (use at least two patient identifiers) and intervention 6 (read
      back of verbal orders) and thus ranked them highly, especially for
      implementability. Intervention 3 (24-hour pharmacist coverage) was ranked low,
      especially on implementability. Interventions involving health information
      technology were ranked lower by the hospitals than by the expert panel.
      DISCUSSION: Safety interventions should reflect the general state of the science
      of safe practices while incorporating relevant contextual issues unique to rural
      hospitals. The results have important implications for survey and accreditation
      activity, and the focus of technical assistance and research efforts.

PMID- 17220160
TI  - The Hospital Overall Flow Scorecard: an innovative tool in patient flow.

PMID- 17220161
TI  - Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive
      summary. The Task Force on Diabetes and Cardiovascular Diseases of the European
      Society of Cardiology (ESC) and of the European Association for the Study of
      Diabetes (EASD).

PMID- 17220162
TI  - Combined effect of pH and concentration on the activities of gentamicin and
      oxacillin against Staphylococcus aureus in pharmacodynamic models of
      extracellular and intracellular infections.
AB  - BACKGROUND: Staphylococcus aureus survives in acid media, including
      phagolysosomes. Conflicting in vitro/in vivo data exist on its susceptibility to
      antibiotics in such environments. METHODS: Oxacillin and gentamicin activities
      against methicillin-susceptible S. aureus ATCC 25923 were compared
      extracellularly (broth; different pH) and assessed intracellularly (THP-1
      macrophages), using a pharmacological approach (antibiotic concentrations: 0.01
      1000 x MIC). Antibiotic cellular contents were determined by microbiological
      assay. RESULTS: MICs and MBCs increased 72-fold for gentamicin, and decreased 8
      fold for oxacillin between pH 7.4 and 5.0. Plots of log(10) colony-forming unit
      changes at 24 h versus log(10) of antibiotic concentration followed sigmoidal
      shapes, allowing calculation of EC(50) (relative potency) and apparent E(max)
      (relative efficacy) in all conditions. In broth, the EC(50) of gentamicin rose
      316-fold and that of oxacillin decreased 15-fold with unchanged apparent E(max) [
      5 log (limit of detection)] between pH 7.4 and 5. Intracellularly, EC(50)s were
      similar to those observed extracellularly at pH 7.4, but E(max) values were much
      lower (-1 log) for both antibiotics. Calculations based on the assumed pH in
      phagolysosomes (5.4) and on local accumulation of antibiotics (gentamicin, 23
      fold; oxacillin, 0.05-fold) suggest that the contrasting effects of acid pH on
      relative potencies of gentamicin and oxacillin could be almost exactly
      compensated for by differences in accumulation. CONCLUSIONS: The weak activity of
      gentamicin and oxacillin towards intraphagocytic S. aureus compared with
      extracellular forms is not related to an overall decrease of their relative
      potencies but to impaired efficacy, suggesting the need for new approaches to
      improve the eradication of intracellular S. aureus.

PMID- 17220163
TI  - Concentration-dependent effects of a selective estrogen receptor modulator
      raloxifene on proliferation and apoptosis in human uterine leiomyoma cells
      cultured in vitro.
AB  - BACKGROUND: This study was conducted to elucidate the effects of raloxifene on
      proliferation and apoptosis in cultured human uterine leiomyoma cells. METHODS:
      The monolayer cultures were treated with graded concentrations (10(-9), 10(-8)
      and 10(-7) M) of raloxifene and 10(-7) M 17beta-estradiol (E(2)). Cell viability,
      percentage of proliferating cell nuclear antigen (PCNA)-positive cells,
      percentage of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'
      triphosphate nick-end labelling (TUNEL)-positive cells and the expression of PCNA
      and Bcl-2 proteins were assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxylphenyl)-2-(4-sulphophenyl)-2H-tetraz olium assay,
      immunocytochemistry, TUNEL assay and western blot analysis, respectively.
      RESULTS: Compared with untreated cultures, the number of viable cultured cells,
      percentage of PCNA-positive cells and PCNA protein expression were significantly
      decreased by treatment with 10(-9) M raloxifene, but increased by treatment with
      either 10(-8) M or 10(-7) M raloxifene. In contrast, the percentage of TUNEL
      positive cells was significantly increased and Bcl-2 protein expression was
      significantly decreased by treatment with 10(-9) M raloxifene, whereas they were
      not affected by treatment with either 10(-8) or 10(-7) M raloxifene. CONCLUSIONS:
      In cultured leiomyoma cells, low concentration (10(-9) M) of raloxifene may
      inhibit the growth of leiomyoma cells, whereas high concentrations (10(-8) M, 10(
      7) M) of raloxifene may promote their growth.

PMID- 17220164
TI  - Psychosocial adjustment during pregnancy for older couples conceiving through
      assisted reproductive technology.
AB  - BACKGROUND: The trend to older maternal age at first birth is well established in
      Western countries and biological risk factors, particularly declining fertility,
      are well documented. Less is known, however, about the psychosocial well-being of
      older first time parents. This study explores differences in psychosocial
      adjustment during pregnancy in older (maternal age >or= 38 years) and younger
      (maternal age < 35 years) couples after assisted reproductive technology (ART)
      conception. METHODS: Questionnaire data were collected from a consecutive cohort
      of pregnant nulliparous women and their partners recruited over a 12-month period
      from ART clinics in Sydney, Australia. RESULTS: There were more similarities than
      differences when comparing older and younger couples. Older couples took longer
      to conceive and were more likely to use donor eggs. Older pregnant women scored
      higher on a measure of psychological hardiness/resilience and reported a lower
      identification with motherhood compared with younger pregnant women. Older men
      differed only in reporting a less satisfying social orientation during pregnancy
      (lower satisfaction with sex life, relationship with partner and social life).
      CONCLUSIONS: Findings do not indicate problematic adjustment during pregnancy in
      older couples, but differences found need further investigation using larger
      samples and prospective designs.

PMID- 17220165
TI  - High prevalence of testicular cancer in azoospermic men without spermatogenesis.
AB  - BACKGROUND: An increased risk of testicular cancer in men with infertility and
      poor semen quality has been reported. Our aim was to investigate the prevalence
      of testicular nodules and cancer in azoospermic subjects with different
      spermatogenetic patterns. METHODS: A total of 1443 consecutive infertile men were
      investigated, out of which 145 (10.0%) were found to be azoospermic. By using
      clinical examination and testicular ultrasound, 11 out of the 145 patients showed
      testicular nodules (2.8-26 mm). To obtain spermatozoa for assisted reproduction,
      97 subjects required testicular sperm extraction (TESE) and biopsy, including the
      11 patients with nodules. They were divided into two groups according to biopsy
      results: Group A (n = 38) with complete Sertoli cell-only syndrome (SCOS) and
      Group B (n = 59) with varying spermatogenetic patterns. Ten nodules were found in
      Group A and one in Group B. RESULTS: In azoospermic men, the overall prevalence
      of nodules was 7.5%. In complete SCOS, the prevalence of nodules and cancer was
      10/38 (26.3%) and 4/38 (10.5%), respectively. Amongst the cancers, one embryonal
      carcinoma, one seminoma and two in-situ carcinomas were found. CONCLUSION: The
      prevalence of testicular nodules and cancer in azoospermic men with complete SCOS
      is very high. In these subjects, the role of clinical evaluation, ultrasound and
      biopsy should be emphasized.

PMID- 17220166
TI  - Assessment of vascular calcification with computed tomography and simple imaging
      tools.

PMID- 17220167
TI  - Does erythropoetin improve survival in ESRD haemodialysis patients?

PMID- 17220168
TI  - From the heart to the soul.

PMID- 17220169
TI  - Extreme context specificity in differential allelic expression.
AB  - Variability in cis-regulation of gene expression has been implicated in the
      phenotypic manifestation of complex traits including common, multifactorial
      diseases. The differential expression of alleles due to polymorphism in cis
      regulatory elements is common in the human genome, but there is a paucity of
      information about the context specificity of these control elements. In this
      study, we examined the differential allelic expression (DAE) of BMP5 in human
      mesenchymal tissues obtained from 16 donors undergoing joint replacement for
      treatment of osteoarthritis. We observed significant differences in BMP5 allelic
      output, with allelic ratios greater than 4:1 (P < 10(-20)) in the tissues of some
      donors. We also discovered a significant variability in allelic expression within
      the different tissues of donors. For 12 of our donors, we examined the allelic
      expression of BMP5 in two different regions of cartilage: cartilage adjacent to
      the site of the osteoarthritic lesion and cartilage distal from the lesion. Five
      of these 12 donors demonstrated highly significant differences (P < or = 10(-8))
      in allelic expression between the different regions of their cartilage. Using DAE
      as a phenotype, we attempted to map tissue-specific cis-regulatory polymorphisms,
      and we identified a single nucleotide polymorphism located downstream of BMP5,
      which was significantly associated with DAE in some but not all of the examined
      tissues. These findings suggest that allelic expression can be highly context
      specific and that when interrogating the cis-regulatory control of a particular
      gene, one cannot necessarily assume that allelic expression is conserved across
      different tissues or even across different regions of the same tissue.

PMID- 17220170
TI  - The ongoing adaptive evolution of ASPM and Microcephalin is not explained by
      increased intelligence.
AB  - Recent studies have made great strides towards identifying putative genetic
      events underlying the evolution of the human brain and its emergent cognitive
      capacities. One of the most intriguing findings is the recurrent identification
      of adaptive evolution in genes associated with primary microcephaly, a
      developmental disorder characterized by severe reduction in brain size and
      intelligence, reminiscent of the early hominid condition. This has led to the
      hypothesis that the adaptive evolution of these genes has contributed to the
      emergence of modern human cognition. As with other candidate loci, however, this
      hypothesis remains speculative due to the current lack of methodologies for
      characterizing the evolutionary function of these genes in humans. Two primary
      microcephaly genes, ASPM and Microcephalin, have been implicated not only in the
      adaptive evolution of the lineage leading to humans, but in ongoing selective
      sweeps in modern humans as well. The presence of both the putatively adaptive and
      neutral alleles at these loci provides a unique opportunity for using normal
      trait variation within humans to test the hypothesis that the recent selective
      sweeps are driven by an advantage in cognitive abilities. Here, we report a large
      scale association study between the adaptive alleles of these genes and normal
      variation in several measures of IQ. Five independent samples were used, totaling
      2393 subjects, including both family-based and population-based datasets. Our
      overall findings do not support a detectable association between the recent
      adaptive evolution of either ASPM or Microcephalin and changes in IQ. As we enter
      the post-genomic era, with the number of candidate loci underlying human
      evolution growing rapidly, our findings highlight the importance of direct
      experimental validation in elucidating their evolutionary role in shaping the
      human phenotype.

PMID- 17220171
TI  - Stat5 constitutive activation rescues defects in spinal muscular atrophy.
AB  - Proximal spinal muscular atrophy (SMA) is a motor neuron degeneration disorder
      for which there is currently no effective treatment. Here, we report three
      compounds (sodium vanadate, trichostatin A and aclarubicin) that effectively
      enhance SMN2 expression by inducing Stat5 activation in SMA-like mouse embryonic
      fibroblasts and human SMN2-transfected NSC34 cells. We found that Stat5
      activation enhanced SMN2 promoter activity with increase in both full-length and
      deletion exon 7 SMN transcripts in SMN2-NSC34 cells. Knockdown of Stat5
      expression disrupted the effects of sodium vanadate on SMN2 activation but did
      not influence SMN2 splicing, suggesting that Stat5 signaling is involved in SMN2
      transcriptional regulation. In addition, constitutive activation of Stat5 mutant
      (Stat5A1*6) profoundly increased the number of nuclear gems in SMA-patient
      lymphocytes and reduced SMA-like motor neuron axon outgrowth defects. These
      results demonstrate that Stat5 signaling could be a possible pharmacological
      target for treating SMA.

PMID- 17220172
TI  - A new inborn error of glycosylation due to a Cog8 deficiency reveals a critical
      role for the Cog1-Cog8 interaction in COG complex formation.
AB  - The hetero-octameric conserved oligomeric Golgi (COG) complex is essential for
      the structure/function of the Golgi apparatus through regulation of membrane
      trafficking. Here, we describe a patient with a mild form of a congenital
      disorder of glycosylation type II (CDG-II), which is caused by a homozygous
      nonsense mutation in the hCOG8 gene. This leads to a premature stop codon
      resulting in a truncated Cog8 subunit lacking the 76 C-terminal amino acids. Mass
      spectrometric analysis of the N- and O-glycan structures identified a mild
      sialylation deficiency. We showed that the molecular basis of this defect in N-
      and O-glycosylation is caused by the disruption of the Cog1-Cog8 interaction due
      to truncation. As a result, Cog1 deficiency accompanies the Cog8 deficiency,
      preventing assembly of the intact, stable complex and resulting in the appearance
      of smaller subcomplexes. Moreover, levels of beta1,4-galactosytransferase were
      significantly reduced. The defects in O-glycosylation could be fully restored by
      transfecting the patient's fibroblasts with full-length Cog8. The Cog8 defect
      described here represents a novel type of CDG-II, which we propose to name as CDG
      IIh or CDG caused by Cog8 deficiency (CDG-II/Cog8).

PMID- 17220173
TI  - Effects of genome-wide heterozygosity on a range of biomedically relevant human
      quantitative traits.
AB  - The dramatic changes in human population structure over the last 200 years have
      resulted in significant levels of outbreeding, which, in turn, is predicted to
      lead to increased levels of individual genetic diversity (genome-wide
      heterozygosity, h). To investigate possible effects of these large demographic
      changes on global health, we studied the effect of h, measured as relative
      heterozygosity, h(R), on 15 disease-related traits in four groups of individuals
      with widely differing ancestral histories (ranging from outbred to inbred) from
      the Dalmatian islands in Croatia. Higher levels of h(R), estimated using 1184
      STR/indel markers, were found in the outbred group (P < 0.0001) and were
      associated with lower blood pressure (BP) and total/LDL cholesterol (P = 0.01 and
      0.01, respectively) after controlling for other factors, with BP showing a strong
      sex effect (males P > 0.5 and females P = 0.002). These findings, if replicated,
      suggest that h(R) be considered as a genetic risk factor in genetic
      epidemiological studies on common disease traits. They are consistent with the
      well-known effects of heterosis (hybrid vigour) described when outcrossing
      animals and plants. Outbreeding resulting from urbanization and migration from
      traditional population subgroups may be leading to increasing h(R) and may have
      beneficial effects on a range of traits associated with human health and disease.
      Other traits, such as age at menarche, IQ and lifespan, which have been changing
      during the decades of urbanization, may also have been influenced by demographic
      factors.

PMID- 17220174
TI  - Cohort profile: the Florey Adelaide Male Ageing Study (FAMAS).

PMID- 17220177
TI  - Endogenous and exogenous NO attenuates conduction of vasoconstrictions along
      arterioles in the microcirculation.
AB  - Vascular coordination in the microcirculation depends on gap junctional
      intercellular communication (GJIC), which is reflected by the conduction of
      locally initiated vasomotor responses. However, little is known about the
      regulation of GJIC in vivo. We hypothesized that endothelial NO regulates GJIC
      and therefore studied whether conduction of constrictions and dilations along the
      vessel wall is modulated by modifying the level of microcirculatory NO.
      Arterioles were focally stimulated using high K(+) or acetylcholine in the
      cremaster muscle in situ, and diameter changes were assessed at the local and
      remote upstream sites by intravital microscopy. Local stimulation with K(+)
      initiated a constriction that conducted along the arteriole with diminishing
      amplitude (length constant lambda: 371 +/- 42 mum). After N(omega)-nitro-l
      arginine (l-NNA), lambda increased to 507 +/- 30 mum, indicating that GJIC is
      attenuated by endogenous NO. Exogenous NO, but not adenosine, reduced lambda
      after l-NNA in a reversible, concentration-dependent, and mainly cGMP-dependent
      manner as assessed by inhibition of soluble guanylate cyclase. In endothelial NO
      synthase-deficient mice, lambda was 530 +/- 80 mum and thus similar to that in
      wild-type mice after l-NNA. Exogenous NO likewise reduced lambda in these mice.
      The effects of NO were comparable to those of wild-type animals in Cx40-deficient
      mice, which excludes Cx40 as a specific target of NO. In contrast to
      constrictions, the amplitude of conducted dilations on acetylcholine did not
      diminish up to 1,300 mum and were not altered by l-NNA or exogenous NO. We
      conclude that endogenously released NO attenuates the conduction of
      vasoconstrictions most likely due to a modulation of gap junctional conductivity.
      We suggest that this effect is specific for smooth muscle cells, which probably
      transmit constricting signals, and involves connexins other than Cx40. This
      mechanism may support the dilatory potency of NO by preventing the conduction of
      remote vasoconstrictions into areas with basal or activated NO release.

PMID- 17220176
TI  - Rho kinase activation plays a major role as a mediator of irreversible injury in
      reperfused myocardium.
AB  - Intracellular signal transduction events in reperfusion following ischemia
      influence myocardial infarct development. Here we investigate the role of Rho
      kinase (ROCK) activation as a specific injury signal during reperfusion via
      attenuation of the reperfusion injury salvage kinase (RISK) pathway
      phosphatidylinositol 3-kinase (PI3K)/Akt/endothelial nitric oxide (NO) synthase
      (eNOS). Rat isolated hearts underwent 35 min of left coronary artery occlusion
      and 120 min of reperfusion. Phosphorylation of the ROCK substrate protein complex
      ezrin-radixin-moesin, assessed by immunoblotting and immunofluorescence, was used
      as a marker of ROCK activation. Infarct size was determined by tetrazolium
      staining, and terminal dUTP nick-end labeling (TUNEL) positivity was used as an
      index of apoptosis. The ROCK inhibitors fasudil or Y-27632 given 10 min before
      ischemia until 10 min after reperfusion reduced infarct size (control, 34.1 +/-
      3.8%; 5 microM fasudil, 18.2 +/- 3.1%; 0.3 microM Y-27632, 19.4 +/- 4.4%; 5
      microM Y-27632, 9.2 +/- 2.9%). When 5 microM Y-27632 was targeted specifically
      during early reperfusion, robust infarct limitation was observed (14.2 +/- 2.6%
      vs. control 33.4 +/- 4.4%, P<0.01). The protective action of Y-27632 given at
      reperfusion was attenuated by wortmannin (29.2 +/- 6.1%) and N(omega)-nitro-L
      arginine methyl ester (30.4 +/- 5.7%), confirming a protective mechanism
      involving PI3K/Akt/NO. Ezrin-radixin-moesin phosphorylation in risk zone
      myocardium confirmed early and sustained ROCK activation during reperfusion and
      its inhibition by Y-27632. Inhibition of ROCK activation at reperfusion reduced
      the proportion of TUNEL-positive nuclei in the infarcted region. In conclusion,
      ROCK activation occurs specifically during early reperfusion. Inhibition of ROCK
      at reperfusion onset limits infarct size through an Akt/eNOS-dependent mechanism,
      suggesting that ROCK activation at reperfusion may be deleterious through
      suppression of the RISK pathway.

PMID- 17220178
TI  - Targeted gene transfer increases contractility and decreases oxygen cost of
      contractility in normal rat hearts.
AB  - The aim of this study was to examine how global cardiac gene transfer of
      sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) can influence left ventricular
      (LV) mechanical and energetic function, especially in terms of O(2) cost of LV
      contractility, in normal rats. Normal rats were randomized to receive an
      adenovirus carrying the SERCA2a (SERCA) or beta-galactosidase (beta-Gal) gene or
      saline by a catheter-based technique. LV mechanical and energetic function was
      measured in cross-circulated heart preparations 2-3 days after the infection. The
      end-systolic pressure-volume relation was shifted upward, end-systolic pressure
      at 0.1 ml of intraballoon water volume was higher, and equivalent maximal
      elastance, i.e., enhanced LV contractility, was higher in the SERCA group than in
      the normal, beta-Gal, and saline groups. Moreover, the LV relaxation rate was
      faster in the SERCA group. There was no significant difference in myocardial O(2)
      consumption per beat-systolic pressure-volume area relation among the groups.
      Finally, O(2) cost of LV contractility was decreased to subnormal levels in the
      SERCA group but remained unchanged in the beta-Gal and saline groups. This
      lowered O(2) cost of LV contractility in SERCA hearts indicates energy saving in
      Ca(2+) handling during excitation-contraction coupling. Thus overexpression of
      SERCA2a transformed the normal energy utilization to a more efficient state in
      Ca(2+) handling and superinduced the supranormal contraction/relaxation due to
      enhanced Ca(2+) handling.

PMID- 17220179
TI  - Resveratrol increases vascular oxidative stress resistance.
AB  - Epidemiological studies suggest that Mediterranean diets rich in resveratrol are
      associated with reduced risk of coronary artery disease. However, the mechanisms
      by which resveratrol exerts its vasculoprotective effects are not completely
      understood. Because oxidative stress and endothelial cell injury play a critical
      role in vascular aging and atherogenesis, we evaluated whether resveratrol
      inhibits oxidative stress-induced endothelial apoptosis. We found that oxidized
      LDL and TNF-alpha elicited significant increases in caspase-3/7 activity in
      endothelial cells and cultured rat aortas, which were prevented by resveratrol
      pretreatment (10(-6)-10(-4) mol/l). The protective effect of resveratrol was
      attenuated by inhibition of glutathione peroxidase and heme oxygenase-1,
      suggesting a role for antioxidant systems in the antiapoptotic action of
      resveratrol. Indeed, resveratrol treatment protected cultured aortic segments
      and/or endothelial cells against increases in intracellular H(2)O(2) levels and
      H(2)O(2)-mediated apoptotic cell death induced by oxidative stressors (exogenous
      H(2)O(2), paraquat, and UV light). Resveratrol treatment also attenuated UV
      induced DNA damage (comet assay). Resveratrol treatment upregulated the
      expression of glutathione peroxidase, catalase, and heme oxygenase-1 in cultured
      arteries, whereas it had no significant effect on the expression of SOD isoforms.
      Resveratrol also effectively scavenged H(2)O(2) in vitro. Thus resveratrol seems
      to increase vascular oxidative stress resistance by scavenging H(2)O(2) and
      preventing oxidative stress-induced endothelial cell death. We propose that the
      antioxidant and antiapoptotic effects of resveratrol, together with its
      previously described anti-inflammatory actions, are responsible, at least in
      part, for its cardioprotective effects.

PMID- 17220180
TI  - Restoration of coronary endothelial function in obese Zucker rats by a low
      carbohydrate diet.
AB  - A popular diet used for weight reduction is the low-carbohydrate diet, which has
      most calories derived from fat and protein, but effects of this dietary regimen
      on coronary vascular function have not been identified. We tested the hypothesis
      that obesity-induced impairment in coronary endothelial function is reversed by a
      low-carbohydrate diet. We used four groups of male Zucker rats: lean and obese on
      normal and low-carbohydrate diets. Rats were fed ad libitum for 3 wk; total
      caloric intake and weight gain were similar in both diets. To assess endothelial
      and vascular function, coronary arterioles were cannulated and pressurized for
      diameter measurements during administration of acetylcholine or sodium
      nitroprusside or during flow. When compared with lean rats, endothelium-dependent
      acetylcholine-induced vasodilation was impaired by approximately 50% in obese
      rats (normal diet), but it was restored to normal by the low-carbohydrate diet.
      When the normal diet was fed, flow-induced dilation (FID) was impaired by >50% in
      obese compared with lean rats. Similar to acetylcholine, responses to FID were
      restored to normal by a low-carbohydrate diet. N(omega)-nitro-L-arginine methyl
      ester (10 microM), an inhibitor of nitric oxide (NO) synthase, inhibited
      acetylcholine- and flow-induced dilation in lean rats, but it had no effect on
      acetylcholine- or flow-induced vasodilation in obese rats on a low-carbohydrate
      diet. Tetraethylammonium, a nonspecific K(+) channel antagonist, blocked flow
      dependent dilation in the obese rats, suggesting that the improvement in function
      was mediated by a hyperpolarizing factor independent of NO. In conclusion,
      obesity-induced impairment in endothelium-dependent vasodilation of coronary
      arterioles can be dramatically improved with a low-carbohydrate diet most likely
      through the production of a hyperpolarizing factor independent of NO.

PMID- 17220175
TI  - Ubiquitin, hormones and biotic stress in plants.
AB  - BACKGROUND: The covalent attachment of ubiquitin to a substrate protein changes
      its fate. Notably, proteins typically tagged with a lysine48-linked polyubiquitin
      chain become substrates for degradation by the 26S proteasome. In recent years
      many experiments have been performed to characterize the proteins involved in the
      ubiquitylation process and to identify their substrates, in order to understand
      better the mechanisms that link specific protein degradation events to regulation
      of plant growth and development. SCOPE: This review focuses on the role that
      ubiquitin plays in hormone synthesis, hormonal signalling cascades and plant
      defence mechanisms. Several examples are given of how targeted degradation of
      proteins affects downstream transcriptional regulation of hormone-responsive
      genes in the auxin, gibberellin, abscisic acid, ethylene and jasmonate signalling
      pathways. Additional experiments suggest that ubiquitin-mediated proteolysis may
      also act upstream of the hormonal signalling cascades by regulating hormone
      biosynthesis, transport and perception. Moreover, several experiments demonstrate
      that hormonal cross-talk can occur at the level of proteolysis. The more recently
      established role of the ubiquitin/proteasome system (UPS) in defence against
      biotic threats is also reviewed. CONCLUSIONS: The UPS has been implicated in the
      regulation of almost every developmental process in plants, from embryogenesis to
      floral organ production probably through its central role in many hormone
      pathways. More recent evidence provides molecular mechanisms for hormonal cross
      talk and links the UPS system to biotic defence responses.

PMID- 17220181
TI  - Role of interleukin-6 in cardiac inflammation and dysfunction after burn
      complicated by sepsis.
AB  - To examine the role of myocardial interleukin-6 (IL-6) in myocardial inflammation
      and dysfunction after burn complicated by sepsis, we performed 40% total body
      surface area contact burn followed by late (7 days) Streptococcus pneumoniae
      pneumonia sepsis in wild-type (WT) mice, IL-6 knockout (IL-6 KO) mice, and
      transgenic mice overexpressing IL-6 in the myocardium (TG). Twenty-four hours
      after sepsis was induced, isolated cardiomyocytes were harvested and cultured in
      vitro, and supernatant concentrations of IL-6 and tumor necrosis factor (TNF)
      alpha were measured. Cardiomyocyte intracellular calcium ([Ca(2+)](i)) and sodium
      ([Na(+)](i)) concentrations were also determined. Separate mice in each group
      underwent in vivo global hemodynamic and cardiac function assessment by
      cannulation of the carotid artery and insertion of a left ventricular pressure
      volume conductance catheter. Hearts from these mice were collected for
      histopathological assessment of inflammatory response, fibrosis, and apoptosis.
      In the WT group, there was an increase in cardiomyocyte TNF-alpha, [Ca(2+)](i),
      and [Na(+)](i) after burn plus sepsis, along with cardiac contractile
      dysfunction, inflammation, and apoptosis. These changes were attenuated in the IL
      6 KO group but accentuated in the TG group. We conclude myocardial IL-6 mediates
      cardiac inflammation and contractile dysfunction after burn plus sepsis.

PMID- 17220183
TI  - Frequency-dependent effects of various IKr blockers on cardiac action potential
      duration in a human atrial model.
AB  - Rapidly activating K(+) current (I(Kr)) blockers prolong action potential (AP)
      duration (APD) in a reverse-frequency-dependent manner and may induce
      arrhythmias, including torsade de pointes in the ventricle. The I(Kr) blocker
      dofetilide has been approved for treatment of atrial arrhythmias, including
      fibrillation. There are, however, a limited number of studies on the action of
      I(Kr) blockers on atrial AP. When we tested a mathematical model of the human
      atrial AP (M Courtemanche, RJ Ramirez, S Nattel. Am J Physiol Heart Circ Physiol
      275: H301-H321, 1998) to examine the effects of dofetilide-type I(Kr) blockade,
      this model could not reproduce the reverse-frequency-dependent nature of I(Kr)
      blockade on atrial APD. We modified the model by introducing a slowly activating
      K(+) current activation parameter. As the slow time constant was increased,
      dofetilide-type blockade induced more prominent reverse-frequency-dependent APD
      prolongation. Using the modified model, we also examined the effects of two more
      types of I(Kr) blockade similar to those of quinidine and vesnarinone. Voltage-
      and time-dependent block of I(Kr) through the onset of inhibition by quinidine is
      much faster than by vesnarinone. When we incorporated the kinetics of the effects
      of these drugs on I(Kr) into the model, we found that quinidine-type blockade
      caused a reverse-frequency-dependent prolongation of APD that was similar to the
      effect of dofetilide-type blockade, whereas vesnarinone-type blockade did not.
      This finding coincides with experimental observations. The lack of the reverse
      frequency dependence in vesnarinone-type blockade was accounted for by the slow
      development of I(Kr) blockade at depolarized potentials. These results suggest
      that the voltage- and time-dependent nature of I(Kr) blockade by drugs may be
      critical for the phenotype of the drug effect on atrial AP.

PMID- 17220184
TI  - E-wave deceleration time may not provide an accurate determination of LV chamber
      stiffness if LV relaxation/viscoelasticity is unknown.
AB  - Average left ventricular (LV) chamber stiffness (Delta P(avg)/Delta V(avg)) is an
      important diastolic function index. An E-wave-based determination of Delta
      P(avg)/Delta V(avg) (Little WC, Ohno M, Kitzman DW, Thomas JD, Cheng CP.
      Circulation 92: 1933-1939, 1995) predicted that deceleration time (DT) determines
      stiffness as follows: Delta P(avg)/Delta V(avg) = N(pi/DT)(2) (where N is
      constant), which implies that if the DTs of two LVs are indistinguishable, their
      stiffness is indistinguishable as well. We observed that LVs with
      indistinguishable DTs may have markedly different Delta P(avg)/Delta V(avg)
      values determined by simultaneous echocardiography-catheterization. To elucidate
      the mechanism by which LVs with indistinguishable DTs manifest distinguishable
      chamber stiffness, we use a validated, kinematic E-wave model (Kovacs SJ,
      Barzilai B, Perez JE. Am J Physiol Heart Circ Physiol 252: H178-H187, 1987) with
      stiffness (k) and relaxation/viscoelasticity (c) parameters. Because the
      predicted linear relation between k and Delta P(avg)/Delta V(avg) has been
      validated, we reexpress the DT-stiffness (Delta P(avg)/Delta V(avg)) relation of
      Little et al. as follows: DT(k) approximately pi/(2k). Using the kinematic model,
      we derive the general DT-chamber stiffness/viscoelasticity relation as follows:
      DT(k,c) = pi/(2skrt[k])+c/(2k)(where c and k are determined directly from the E
      wave), which reduces to DT(k) when c << k. Validation involved analysis of 400 E
      waves by determination of five-beat averaged k and c from 80 subjects undergoing
      simultaneous echocardiography-catheterization. Clinical E-wave DTs were compared
      with model-predicted DT(k) and DT(k,c). Clinical DT was better predicted by
      stiffness and relaxation/viscoelasticity (r(2) = 0.84, DT vs. DT(k,c)) jointly
      rather than by stiffness alone (r(2) = 0.60, DT vs. DT(k)). Thus LVs can have
      indistinguishable DTs but significantly different Delta P(avg)/Delta V(avg) if
      chamber relaxation/viscoelasticity differs. We conclude that DT is a function of
      both chamber stiffness and chamber relaxation viscoelasticity. Quantitative
      diastolic function assessment warrants consideration of simultaneous stiffness
      and relaxation/viscoelastic effects.

PMID- 17220182
TI  - NADPH oxidase modulates myocardial Akt, ERK1/2 activation, and angiogenesis after
      hypoxia-reoxygenation.
AB  - Recent studies have demonstrated that reactive oxygen species (ROS) mediate
      myocardial ischemia-reperfusion (I/R) and angiogenesis via the mitogen-activated
      protein kinases and the serine-threonine kinase Akt/protein kinase B pathways.
      NADPH oxidases are major sources of ROS in endothelial cells and cardiomyocytes.
      In the present study, we investigated the role of NADPH oxidase-derived ROS in
      hypoxia-reoxygenation (H/R)-induced Akt and ERK1/2 activation and angiogenesis
      using porcine coronary artery endothelial cells (PCAECs) and a mouse myocardial
      I/R model. Our data demonstrate that exposure of PCAECs to hypoxia for 2 h
      followed by 1 h of reoxygenation significantly increased ROS formation.
      Pretreatment with the NADPH oxidase inhibitors, diphenyleneiodonium (DPI, 10
      microM) and apocynin (Apo, 200 and 600 microM), significantly attenuated H/R
      induced ROS formation. Furthermore, exposure of PCAECs to H/R caused a
      significant increase in Akt and ERK1/2 activation. Exposure of PCAEC spheroids
      and mouse aortic rings to H/R significantly increased endothelial spheroid
      sprouting and vessel outgrowth, whereas pharmacological inhibition of NADPH
      oxidase or genetic deletion of the NADPH oxidase subunit, p47(phox) (p47(phox-/
      )), significantly suppressed these changes. With the use of a mouse I/R model,
      our data further show that the increases in myocardial Akt and ERK1/2 activation
      and vascular endothelial growth factor (VEGF) expression were markedly blunted in
      the p47(phox-/-) mouse subjected to myocardial I/R compared with the wild-type
      mouse. Our findings underscore the important role of NADPH oxidase and its
      subunit p47(phox) in modulating Akt and ERK1/2 activation, angiogenic growth
      factor expression, and angiogenesis in myocardium undergoing I/R.

PMID- 17220185
TI  - Effect of simultaneous intracoronary guidewires on the predictive accuracy of
      functional parameters of coronary lesion severity.
AB  - The aim of this study was to assess the influence of a second guidewire on the
      diagnostic accuracy of functional parameters of coronary lesion severity. Sixty
      five patients with intermediate coronary lesions underwent myocardial perfusion
      scintigraphy. Fractional flow reserve (FFR), coronary flow velocity reserve
      (CFVR), and hyperemic stenosis resistance (HSR) index (HSR = stenosis pressure
      gradient / velocity) were determined in 77 lesions. Distal pressure and velocity
      were acquired simultaneously (dual wire) and sequentially (single wire) with two
      sensor-equipped guidewires. Overall, functional parameters deteriorated from
      single- to dual-wire assessment. In patients without ischemia, the good
      diagnostic performance of FFR, CFVR, and HSR deteriorated significantly (P <
      0.001) when assessed by dual wires, with an increase in the number of false
      positive results. This trend was more pronounced for HSR, since the presence of a
      second wire reduced maximal velocity and increased the pressure gradient. The
      presence of two guidewires, especially across a myocardial perfusion scintigraphy
      induced nonsignificant lesion, is associated with overestimation of the
      hemodynamically assessed lesion severity and, therefore, is likely to have a
      major impact on clinical decision making. This underscores the advantage of a
      dual-sensor-equipped guidewire for the evaluation of stenosis severity by
      combined pressure and velocity measurements.

PMID- 17220186
TI  - p22phox in the macula densa regulates single nephron GFR during angiotensin II
      infusion in rats.
AB  - Angiotensin II (ANG II) infusion increases renal superoxide (O(2)(-)) and
      enhances renal vasoconstriction via macula densa (MD) regulation of
      tubuloglomerular feedback, but the mechanism is unclear. We targeted the
      p22(phox) subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      (NOX) with small-interfering RNA (siRNA) to reduce NADPH oxidase activity and
      blood pressure response to ANG II in rats. We compared single nephron glomerular
      filtration rate (SNGFR) in samples collected from the proximal tubule (PT), which
      interrupts delivery to the MD, and from the distal tubule (DT), which maintains
      delivery to the MD, to assess MD regulation of GFR. SNGFR was measured in control
      and ANG II-infused rats (200 ng.kg(-1).min(-1) for 7 days) 2 days after
      intravenous injection of vehicle or siRNA directed to p22(phox) to test the
      hypothesis that p22(phox) mediates MD regulation of SNGFR during ANG II. The
      regulation of SNGFR by MD, determined by PT SNGFR-DT SNGFR, was not altered by
      siRNA in control rats (control + vehicle, 13 +/- 1, n = 8; control + siRNA, 12 +/
      2 nl/min, n = 8; not significant) but was reduced by siRNA in ANG II-treated
      rats (ANG II + vehicle, 13 +/- 2, n = 7; ANG II + siRNA, 7 +/- 1 nl/min, n = 8; P
      < 0.05). We conclude that p22(phox) and NADPH oxidase regulate the SNGFR during
      ANG II infusion via MD-dependent mechanisms.

PMID- 17220187
TI  - Effects of hypercapnia and hypoxemia on respiratory sinus arrhythmia in conscious
      humans during spontaneous respiration.
AB  - Normally, at rest, the amplitude of respiratory sinus arrhythmia (RSA) appears to
      correlate with cardiac vagal tone. However, recent studies showed that, under
      stress, RSA dissociates from vagal tone, indicating that separate mechanisms
      might regulate phasic and tonic vagal activity. This dissociation has been linked
      to the hypothesis that RSA improves pulmonary gas exchange through preferential
      distribution of heartbeats in inspiration. We examined the effects of hypercapnia
      and mild hypoxemia on RSA-vagal dissociation in relation to heartbeat
      distribution throughout the respiratory cycle in 12 volunteers. We found that
      hypercapnia, but not hypoxemia, was associated with significant increases in
      heart rate (HR), tidal volume, and RSA amplitude. The RSA amplitude increase
      remained statistically significant after adjustment for respiratory rate, tidal
      volume, and HR. Moreover, the RSA amplitude increase was associated with a
      paradoxical rise in HR and decrease in low-frequency-to-high-frequency mean
      amplitude ratio derived from spectral analysis, which is consistent with RSA
      vagal dissociation. Although hypercapnia was associated with a significant
      increase in the percentage of heartbeats during inspiration, this association was
      largely secondary to increases in the inspiratory period-to-respiratory period
      ratio, rather than RSA amplitude. Additional model analyses of RSA were
      consistent with the experimental data. Heartbeat distribution did not change
      during hypoxemia. These results support the concept of RSA-vagal dissociation
      during hypercapnia; however, the putative role of RSA in optimizing pulmonary
      perfusion matching requires further experimental validation.

PMID- 17220188
TI  - Alpha1-adrenoceptor-dependent vascular hypertrophy and remodeling in murine
      hypoxic pulmonary hypertension.
AB  - Excessive proliferation of vascular wall cells underlies the development of
      elevated vascular resistance in hypoxic pulmonary hypertension (PH), but the
      responsible mechanisms remain unclear. Growth-promoting effects of catecholamines
      may contribute. Hypoxemia causes sympathoexcitation, and prolonged stimulation of
      alpha(1)-adrenoceptors (alpha(1)-ARs) induces hypertrophy and hyperplasia of
      arterial smooth muscle cells and adventitial fibroblasts. Catecholamine trophic
      actions in arteries are enhanced when other conditions favoring growth or
      remodeling are present, e.g., injury or altered shear stress, in isolated
      pulmonary arteries from rats with hypoxic PH. The present study examined the
      hypothesis that catecholamines contribute to pulmonary vascular remodeling in
      vivo in hypoxic PH. Mice genetically deficient in norepinephrine and epinephrine
      production [dopamine beta-hydroxylase(-/-) (DBH(-/-))] or alpha(1)-ARs were
      examined for alterations in PH, cardiac hypertrophy, and vascular remodeling
      after 21 days exposure to normobaric 0.1 inspired oxygen fraction (Fi(O(2))). A
      decrease in the lumen area and an increase in the wall thickness of arteries were
      strongly inhibited in knockout mice (order of extent of inhibition: DBH(-/-) =
      alpha(1D)-AR(-/-) > alpha(1B)-AR(-/-)). Distal muscularization of small
      arterioles was also reduced (DBH(-/-) > alpha(1D)-AR(-/-) > alpha(1B)-AR(-/-)
      mice). Despite these reductions, increases in right ventricular pressure and
      hypertrophy were not attenuated in DBH(-/-) and alpha(1B)-AR(-/-) mice. However,
      hematocrit increased more in these mice, possibly as a consequence of impaired
      cardiovascular activation that occurs during reduction of Fi(O(2)). In contrast,
      in alpha(1D)-AR(-/-) mice, where hematocrit increased the same as in wild-type
      mice, right ventricular pressure was reduced. These data suggest that
      catecholamine stimulation of alpha(1B)- and alpha(1D)-ARs contributes
      significantly to vascular remodeling in hypoxic PH.

PMID- 17220189
TI  - Macromolecular transport in heart valves. II. Theoretical models.
AB  - This paper proposes a new, two-dimensional convection-diffusion model for
      macromolecular transport in heart valves based on horseradish peroxidase (HRP)
      experiments on rats presented in the first of the papers in this series (Part I;
      Zeng Z, Yin Y, Huang AL, Jan KM, Rumschitzki DS. Am J Physiol Heart Circ Physiol
      292: H2664-H2670, 2007). Experiments require two valvular intimae, one underneath
      each endothelium. Tompkins et al. (Tompkins RG, Schnitzer JJ, Yarmush ML. Circ
      Res 64: 1213-1223, 1989) found large variations in shape and magnitude in
      transvalvular (125)I-labeled low-density lipoprotein (LDL) profiles from
      identical experiments on four squirrel monkeys. Their one-dimensional, uniform
      medium diffusion-only model fit three parameters independently for each profile;
      data variability resulted in large parameter spreads. Our theory aims to explain
      their data with one parameter set. It uses measured parameters and some aortic
      values but fits the endothelial mass transfer coefficient (k(a)=k(v)=1.63 x 10(
      8) cm/s, where subscripts a and v indicate aortic aspect and ventricular aspect,
      respectively) and middle layer permeability (K(p(2))=2.28 x 10(-16)cm(2)) and LDL
      diffusion coefficient [D(2)(LDL)=5.93 x 10(-9) cm(2)/s], using one of Tompkins et
      al.'s profiles, and fixes them throughout. It accurately predicts Part I's rapid
      localized HRP leakage spot growth rate in rat leaflets that results from the
      intima's much sparser structure, dictating its far larger transport parameters
      [K(p(1))= 1.10 x 10(-12)cm(2), D(1)(LDL/HRP)=1.02/4.09 x 10(-7)cm(2)/s] than the
      middle layer. This contrasts with large arteries with similarly large HRP spots,
      since the valve has no internal elastic lamina. The model quantitatively explains
      all of Tompkins et al.'s monkey profiles with these same parameters. Different
      numbers and locations of isolated macromolecular leaks on both aspects and
      different section-leak(s) distances yield all profiles.

PMID- 17220190
TI  - Angiotensin II type 1 receptor signaling contributes to platelet-leukocyte
      endothelial cell interactions in the cerebral microvasculature.
AB  - Angiotensin II type 1 (AT(1)) receptor signaling has been implicated in cerebral
      microvascular alterations associated with ischemia, diabetes mellitus,
      hypercholesterolemia, and atherosclerosis. Platelets, which express AT(1)
      receptors, also appear to contribute to the thrombogenic and inflammatory
      responses that are elicited by these pathological conditions. This study assesses
      the role of AT(1) receptor activation on platelet-leukocyte-endothelial cell
      interactions elicited in cerebral microvasculature by ischemia and reperfusion.
      Intravital microscopy was used to monitor the adhesion of platelets and
      leukocytes that were labeled with different fluorochromes, whereas
      dihydrorhodamine-123 was used to quantify oxygen radical production in cerebral
      surface of mice that were either treated with the AT(1) receptor agonist Val
      angiotensin II (ANG II) or subjected to bilateral common carotid artery occlusion
      (BCCAO) followed by reperfusion. ANG II elicited a dose- and time- dependent
      increase in platelet-leukocyte-endothelial cell interactions in cerebral venules
      that included rolling platelets, adherent platelets on the leukocytes and the
      endothelial cells, rolling leukocytes, and adherent leukocytes. All of these
      interactions were attenuated by treatment with either P-selectin or P-selectin
      glycoprotein ligand 1 (PSGL-1) antibody. The AT(1) receptor antagonist
      candesartan and losartan as well as diphenyleneiodonium, an inhibitor of
      flavoproteins including NAD(P)H oxidase, significantly reduced the platelet
      leukocyte-endothelial cell interactions elicited by either ANG II administration
      or BCCAO/reperfusion. The increased oxygen radical generation elicited by
      BCCAO/reperfusion was also attenuated by candesartan. These findings are
      consistent with an AT(1) receptor signaling mechanism, which involves oxygen
      radical production and ultimately results in P-selectin- and PSGL-1-mediated
      platelet-leukocyte-endothelial cell interactions in the cerebral
      microcirculation.

PMID- 17220191
TI  - Leptin induces elongation of cardiac myocytes and causes eccentric left
      ventricular dilatation with compensation.
AB  - One of the major manifestations of obesity is an increased production of the
      adipocyte-derived 16-kDa peptide leptin, which acts mainly on hypothalamic leptin
      receptors. Leptin receptors are widely distributed in various tissues, including
      the heart. Whereas increased plasma leptin levels have been reported in patients
      with congestive heart failure, systemic alterations induced by obesity can affect
      cardiac hypertrophy, and the direct effects of leptin on cardiac structure and
      function still remain to be determined. We first exposed primary cardiac myocytes
      from neonatal rats to leptin for 48 h. This resulted in a significant increase in
      myocyte long-axis length (P < 0.05 at 50 ng/ml) but not in the short-axis width.
      Leptin induced the rapid phosphorylation of STAT3 and its DNA binding in cardiac
      myocytes. Administration of a JAK2 inhibitor, AG-490, completely inhibited all of
      these effects by leptin. Furthermore, we examined the effect of continuous
      infusion of leptin for 4 wk following myocardial infarction in mice.
      Echocardiography demonstrated that left ventricular fractional shortening in the
      leptin-infused group (28.4 +/- 2.8%) was significantly higher than that in the
      PBS-infused group (18.4 +/- 2.2%) following myocardial infarction. Interestingly,
      left ventricular diastolic dimension in the leptin-infused group (4.56 +/- 0.12
      mm) was also higher than that in the PBS-infused group (4.13 +/- 0.09 mm). These
      results demonstrate that leptin induces the elongation of cardiac myocytes via a
      JAK/STAT pathway and chronic leptin infusion causes eccentric dilatation with
      augmented systolic function after myocardial infarction.

PMID- 17220192
TI  - Impaired NO-mediated vasodilation with increased superoxide but robust EDHF
      function in right ventricular arterial microvessels of pulmonary hypertensive
      rats.
AB  - Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and,
      according to the extent of pressure overload, eventual heart failure. We tested
      the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of
      the RV coronary microvessels of different sizes with increased superoxide levels.
      Five-week-old male Sprague-Dawley rats were injected with monocrotaline (n=126)
      to induce PH or with saline as controls (n=114). After 3 wk, coronary arterioles
      (diameter = 30-100 microm) and small arteries (diameter = 100-200 microm) in the
      RV were visualized using intravital videomicroscopy. We evaluated ACh-induced
      vasodilation alone, in the presence of N(omega)-nitro-L-arginine methyl ester (L
      NAME), in the presence of tetraethylammonium (TEA) or catalase with or without L
      NAME, and in the presence of SOD. The degree of suppression in vasodilation by L
      NAME and TEA was used as indexes of the contributions of endothelial nitric oxide
      (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH
      rats, ACh-induced vasodilation was significantly attenuated in both arterioles
      and small arteries, especially in arterioles. This decreased vasodilation was
      largely attributable to reduced NO-mediated vasoreactivity, whereas the EDHF
      mediated vasodilation was relatively robust. The suppressive effect on arteriolar
      vasodilation by catalase was similar to TEA in both groups. Superoxide, as
      measured by lucigenin chemiluminescence, was significantly elevated in the RV
      tissues in PH. SOD significantly ameliorated the impairment of ACh-induced
      vasodilation in PH. Robust EDHF function will play a protective role in
      preserving coronary microvascular homeostasis in the event of NO dysfunction with
      increased superoxide levels.

PMID- 17220193
TI  - W-7 modulates Kv4.3: pore block and Ca2+-calmodulin inhibition.
AB  - Ca(+)-calmodulin (Ca(2+)-CaM)-dependent protein kinase II (Ca(2+)/CaMKII) is an
      important regulator of cardiac ion channels, and its inhibition may be an
      approach for treatment of ventricular arrhythmias. Using the two-electrode
      voltage-clamp technique, we investigated the role of W-7, an inhibitor of Ca(2+)
      occupied CaM, and KN-93, an inhibitor of Ca(2+)/CaMKII, on the K(v)4.3 channel in
      Xenopus laevis oocytes. W-7 caused a voltage- and concentration-dependent
      decrease in peak current, with IC(50) of 92.4 muM. The block was voltage
      dependent, with an effective electrical distance of 0.18 +/- 0.05, and use
      dependence was observed, suggesting that a component of W-7 inhibition of K(v)4.3
      current was due to open-channel block. W-7 made recovery from open-state
      inactivation a biexponential process, also suggesting open-channel block. We
      compared the effects of W-7 with those of KN-93 after washout of 500 muM BAPTA
      AM. KN-93 reduced peak current without evidence of voltage or use dependence.
      Both W-7 and KN-93 accelerated all components of inactivation. We used wild-type
      and mutated K(v)4.3 channels with mutant CaMKII consensus phosphorylation sites
      to examine the effects of W-7 and KN-93. In contrast to W-7, KN-93 at 35 muM
      selectively accelerated open-state inactivation in the wild-type vs. the mutant
      channel. W-7 had a significantly greater effect on recovery from inactivation in
      wild-type than in mutant channels. We conclude that, at certain concentrations,
      KN-93 selectively inhibits Ca(2+)/CaMKII activity in Xenopus oocytes and that the
      effects of W-7 are mediated by direct interaction with the channel pore and
      inhibition of Ca(2+)-CaM, as well as a change in activity of Ca(2+)-CaM-dependent
      enzymes, including Ca(2+)/CaMKII.

PMID- 17220194
TI  - Impact of acute and enduring volume overload on mechanotransduction and
      cytoskeletal integrity of canine left ventricular myocardium.
AB  - It is poorly understood how mechanical stimuli influence in vivo myocardial
      remodeling during chronic hemodynamic overload. Combined quantitation of
      ventricular mechanics and expression of key proteins involved in
      mechanotransduction can improve fundamental understanding. Adult anesthetized
      dogs (n = 20) were studied at sinus rhythm (SR) and 0, 3, 10, and 35 days of
      complete atrioventricular block (AVB). Serial left ventricular (LV) myofiber
      mechanics were measured. Repeated LV biopsies were analyzed for mRNA and/or
      protein expression of beta(1D)-integrin, melusin, Akt, GSK3beta, muscle LIM
      protein (MLP), four-and-a-half LIM protein 2 (fhl2), desmin, and calpain. Upon
      AVB, increased ejection strain (0.29 +/- 0.01 vs. 0.13 +/- 0.02, SR) and end
      diastolic stress (4.8 +/- 1.1 vs. 2.7 +/- 0.4 kPa) dominated mechanical changes.
      Brain natriuretic peptide plasma levels were correspondingly high (33 +/- 4 vs.
      19 +/- 1 pg/ml, SR). beta(1D)-Integrin protein expression increased chronically
      after AVB. Melusin was temporarily overexpressed (+33 +/- 9%, 3 days AVB vs. SR),
      followed by elevated ratios of phosphorylated (P)-Akt to Akt and P-GSK3beta to
      GSK3beta (+26 +/- 6% and +30 +/- 8% at 10 days AVB vs. SR). These changes
      corresponded to peak hypertrophic growth at 3 to 10 days. MLP increased gradually
      to maxima at chronic AVB (+36 +/- 7%). In contrast, fhl2 (-22 +/- 3%, 3 days) and
      desmin (-30 +/- 9%, 10 days AVB) transiently declined but recovered at chronic
      AVB. Calpain protein expression remained unaltered. In conclusion, volume
      overload after AVB causes a transient compromise of cytoskeletal integrity based,
      at least partly, on transcriptional downregulation. Subsequent cytoskeletal
      reorganization coincides with the upregulation of melusin, P-Akt, P-GSK3beta, and
      MLP, indicating a strong drive to compensated hypertrophy.

PMID- 17220196
TI  - Repression of flowering in Arabidopsis requires activation of FLOWERING LOCUS C
      expression by the histone variant H2A.Z.
AB  - The histone variant H2A.Z has been implicated in numerous chromatin-mediated
      processes, including transcriptional activation, euchromatin maintenance, and
      heterochromatin formation. In yeast and humans, H2A.Z is deposited into chromatin
      by a conserved protein complex known as SWR1 and SRCAP, respectively. Here, we
      show that mutations in the Arabidopsis thaliana homologs of two components of
      this complex, ACTIN-RELATED PROTEIN6 (ARP6) and PHOTOPERIOD-INDEPENDENT EARLY
      FLOWERING1 (PIE1), produce similar developmental phenotypes and result in the
      misregulation of a common set of genes. Using H2A.Z-specific antibodies, we
      demonstrate that ARP6 and PIE1 are required for the deposition of H2A.Z at
      multiple loci, including the FLOWERING LOCUS C (FLC) gene, a central repressor of
      the transition to flowering. Loss of H2A.Z from chromatin in arp6 and pie1
      mutants results in reduced FLC expression and premature flowering, indicating
      that this histone variant is required for high-level expression of FLC. In
      addition to defining a novel mechanism for the regulation of FLC expression,
      these results support the existence of a SWR1-like complex in Arabidopsis and
      show that H2A.Z can potentiate transcriptional activation in plants. The finding
      that H2A.Z remains associated with chromatin throughout mitosis suggests that it
      may serve an epigenetic memory function by marking active genes and poising
      silenced genes for reactivation.

PMID- 17220197
TI  - A novel transcriptional cascade regulating expression of heat stress proteins
      during seed development of Arabidopsis.
AB  - Within the Arabidopsis thaliana family of 21 heat stress transcription factors
      (Hsfs), HsfA9 is exclusively expressed in late stages of seed development. Here,
      we present evidence that developmental expression of HsfA9 is regulated by the
      seed-specific transcription factor ABSCISIC ACID-INSENSITIVE3 (ABI3).
      Intriguingly, ABI3 knockout lines lack detectable levels of HsfA9 transcript and
      protein, and further ectopic expression of ABI3 conferred the ability to
      accumulate HsfA9 in response to abscisic acid in transgenic plantlets.
      Consequently, the most abundant heat stress proteins (Hsps) in seeds (Hsp17.4-CI,
      Hsp17.7-CII, and Hsp101) were not detectable in the ABI3 knockout lines, but
      their expression could be detected in plants ectopically expressing HsfA9 in
      vegetative tissues. Furthermore, this seed-specific transcription factor cascade
      was reconstructed in transient beta-glucuronidase reporter assays in mesophyll
      protoplasts by showing that ABI3 could activate the HsfA9 promoter, whereas HsfA9
      in turn was shown to be a potent activator on the promoters of Hsp genes. Thus,
      our study establishes a genetic framework in which HsfA9 operates as a
      specialized Hsf for the developmental expression of Hsp genes during seed
      maturation.

PMID- 17220198
TI  - The kinesin ATK5 functions in early spindle assembly in Arabidopsis.
AB  - During cell division, the mitotic spindle partitions chromosomes into daughter
      nuclei. In higher plants, the molecular mechanisms governing spindle assembly and
      function remain largely unexplored. Here, live cell imaging of mitosis in
      Arabidopsis thaliana plants lacking a kinesin-14 (ATK5) reveals defects during
      early spindle formation. Beginning during prophase and lasting until late
      prometaphase, spindles of atk5-1 plants become abnormally elongated, are
      frequently bent, and have splayed poles by prometaphase. The period of spindle
      elongation during prophase and prometaphase is prolonged in atk5-1 cells. Time
      lapse imaging of yellow fluorescent protein:ATK5 reveals colocalization with
      perinuclear microtubules before nuclear envelope breakdown, after which it
      congresses inward from the poles to the midzone, where it becomes progressively
      enriched at regions of overlap between antiparallel microtubules. In vitro
      microtubule motility assays demonstrate that in the presence of ATK5, two
      microtubules encountering one another at an angle can interact and coalign,
      forming a linear bundle. These data indicate that ATK5 participates in the search
      and capture of antiparallel interpolar microtubules, where it aids in generating
      force to coalign microtubules, thereby affecting spindle length, width, and
      integrity.

PMID- 17220199
TI  - The PEROXIN11 protein family controls peroxisome proliferation in Arabidopsis.
AB  - PEROXIN11 (PEX11) is a peroxisomal membrane protein in fungi and mammals and was
      proposed to play a major role in peroxisome proliferation. To begin understanding
      how peroxisomes proliferate in plants and how changes in peroxisome abundance
      affect plant development, we characterized the extended Arabidopsis thaliana
      PEX11 protein family, consisting of the three phylogenetically distinct
      subfamilies PEX11a, PEX11b, and PEX11c to PEX11e. All five Arabidopsis PEX11
      proteins target to peroxisomes, as demonstrated for endogenous and cyan
      fluorescent protein fusion proteins by fluorescence microscopy and
      immunobiochemical analysis using highly purified leaf peroxisomes. PEX11a and
      PEX11c to PEX11e behave as integral proteins of the peroxisome membrane.
      Overexpression of At PEX11 genes in Arabidopsis induced peroxisome proliferation,
      whereas reduction in gene expression decreased peroxisome abundance. PEX11c and
      PEX11e, but not PEX11a, PEX11b, and PEX11d, complemented to significant degrees
      the growth phenotype of the Saccharomyces cerevisiae pex11 null mutant on oleic
      acid. Heterologous expression of PEX11e in the yeast mutant increased the number
      and reduced the size of the peroxisomes. We conclude that all five Arabidopsis
      PEX11 proteins promote peroxisome proliferation and that individual family
      members play specific roles in distinct peroxisomal subtypes and environmental
      conditions and possibly in different steps of peroxisome proliferation.

PMID- 17220200
TI  - PIP5K9, an Arabidopsis phosphatidylinositol monophosphate kinase, interacts with
      a cytosolic invertase to negatively regulate sugar-mediated root growth.
AB  - Phosphatidylinositol monophosphate 5-kinase (PIP5K) plays an essential role in
      coordinating plant growth, especially in response to environmental factors. To
      explore the physiological function of PIP5K, we characterized Arabidopsis
      thaliana PIP5K9, which is constitutively expressed. We found that a T-DNA
      insertion mutant, pip5k9-d, which showed enhanced PIP5K9 transcript levels, had
      shortened primary roots owing to reduced cell elongation. Transgenic plants
      overexpressing PIP5K9 displayed a similar root phenotype. Yeast two-hybrid assays
      identified a cytosolic invertase, CINV1, that interacted with PIP5K9, and the
      physiological relevance of this interaction was confirmed by
      coimmunoprecipitation studies using plant extracts. CINV1-deficient plants,
      cinv1, had reduced activities of both neutral and acid invertases as well as
      shortened roots. Invertase activities in pip5k9-d seedlings were also reduced,
      suggesting a negative regulation of CINV1 by PIP5K9. In vitro studies showed that
      PIP5K9 interaction indeed repressed CINV1 activities. Genome-wide expression
      studies revealed that genes involved in sugar metabolism and multiple
      developmental processes were altered in pip5k9-d and cinv1, and the altered sugar
      metabolism in these mutants was confirmed by metabolite profiling. Together, our
      results indicate that PIP5K9 interacts with CINV1 to negatively regulate sugar
      mediated root cell elongation.

PMID- 17220201
TI  - Methylation of gibberellins by Arabidopsis GAMT1 and GAMT2.
AB  - Arabidopsis thaliana GAMT1 and GAMT2 encode enzymes that catalyze formation of
      the methyl esters of gibberellins (GAs). Ectopic expression of GAMT1 or GAMT2 in
      Arabidopsis, tobacco (Nicotiana tabacum), and petunia (Petunia hybrida) resulted
      in plants with GA deficiency and typical GA deficiency phenotypes, such as
      dwarfism and reduced fertility. GAMT1 and GAMT2 are both expressed mainly in
      whole siliques (including seeds), with peak transcript levels from the middle
      until the end of silique development. Within whole siliques, GAMT2 was previously
      shown to be expressed mostly in developing seeds, and we show here that GAMT1
      expression is also localized mostly to seed, suggesting a role in seed
      development. Siliques of null single GAMT1 and GAMT2 mutants accumulated high
      levels of various GAs, with particularly high levels of GA(1) in the double
      mutant. Methylated GAs were not detected in wild-type siliques, suggesting that
      methylation of GAs by GAMT1 and GAMT2 serves to deactivate GAs and initiate their
      degradation as the seeds mature. Seeds of homozygous GAMT1 and GAMT2 null mutants
      showed reduced inhibition of germination, compared with the wild type, when
      placed on plates containing the GA biosynthesis inhibitor ancymidol, with the
      double mutant showing the least inhibition. These results suggest that the mature
      mutant seeds contained higher levels of active GAs than wild-type seeds.

PMID- 17220202
TI  - Regulation of telomerase in Arabidopsis by BT2, an apparent target of TELOMERASE
      ACTIVATOR1.
AB  - Telomerase, an enzyme essential for the synthesis and maintenance of telomeric
      DNA and the long-term stability of the genome, is developmentally regulated in
      plants. Telomerase activity is abundant in reproductive organs but low or
      undetectable in vegetative organs. Treatment with exogenous auxin, however,
      overrides this developmental control and induces telomerase in mature leaves. The
      Arabidopsis thaliana transcription factor TELOMERASE ACTIVATOR1 (TAC1)
      potentiates some responses to auxin, including the induction of telomerase
      activity in leaves. Here, we report that BT2, a protein with BTB, TAZ, and
      calmodulin binding domains, is an essential component of the TAC1-mediated
      telomerase activation pathway. Steady state concentration of BT2 mRNA increases
      in response to TAC1 expression, and TAC1 specifically binds the BT2 promoter both
      in vitro and in yeast one-hybrid assays. Constitutive expression of BT2 induces
      telomerase activity in leaves, whereas a null mutation of BT2 blocks TAC1
      mediated telomerase induction, indicating that BT2 acts downstream of TAC1 to
      regulate telomerase activity in mature vegetative organs.

PMID- 17220203
TI  - Chlamydomonas reinhardtii has multiple prolyl 4-hydroxylases, one of which is
      essential for proper cell wall assembly.
AB  - Prolyl 4-hydroxylases (P4Hs) catalyze formation of 4-hydroxyproline (4Hyp), which
      is found in many plant glycoproteins. We cloned and characterized Cr-P4H-1, one
      of 10 P4H-like Chlamydomonas reinhardtii polypeptides. Recombinant Cr-P4H-1 is a
      soluble 29-kD monomer that effectively hydroxylated in vitro both poly(l-Pro) and
      synthetic peptides representing Pro-rich motifs found in the Chlamydomonas cell
      wall Hyp-rich glycoprotein (HRGP) GP1. Similar Pro-rich repeats that are likely
      to be Cr-P4H-1 substrates are also present in the cell wall HRGP GP2 and probably
      GP3. Suppression of the gene encoding Cr-P4H-1 by RNA interference led to a
      defective cell wall consisting of a loose network of fibrils resembling the inner
      and outer W1 and W7 layers of the wild-type wall, while the layers forming the
      dense central triplet were absent. The lack of Cr-P4H-1 most probably affected
      4Hyp content of the major HRPGs of the central triplet, GP1, GP2, and GP3. The
      reduced 4Hyp levels in these HRGPs can also be expected to affect their
      glycosylation and, thus, the interactive properties and stabilities of their
      fibrous shafts. Interestingly, our RNA interference data indicate that the nine
      other Chlamydomonas P4H-like polypeptides could not fully compensate for the lack
      of Cr-P4H-1 activity and are therefore likely to have different substrate
      specificities and functions.

PMID- 17220204
TI  - Characterization of the SP11/SCR high-affinity binding site involved in
      self/nonself recognition in brassica self-incompatibility.
AB  - In Brassica self-incompatibility, the recognition of self/nonself pollen grains,
      is controlled by the S-locus, which encodes three highly polymorphic proteins: S
      locus receptor kinase (SRK), S-locus protein 11 (SP11; also designated S-locus
      Cys-rich protein), and S-locus glycoprotein (SLG). SP11, located in the pollen
      coat, determines pollen S-haplotype specificity, whereas SRK, located on the
      plasma membrane of stigmatic papilla cells, determines stigmatic S-haplotype
      specificity. SLG shares significant sequence similarity with the extracellular
      domain of SRK and is abundant in the stigmatic cell wall, but its function is
      controversial. We previously showed that SP11 binds directly to its cognate SRK
      with high affinity (K(d) = 0.7 nM) and induces its autophosphorylation. We also
      found that an SLG-like, 60-kD protein on the stigmatic membrane forms a high
      affinity binding site for SP11. Here, we show that the 60-kD stigmatic membrane
      protein is a truncated form of SRK containing the extracellular domain,
      transmembrane domain, and part of the juxtamembrane domain. A transiently
      expressed, membrane-anchored form of SRK exhibits high-affinity binding to SP11,
      whereas the soluble SRK (eSRK) lacking the transmembrane domain exhibits no high
      affinity binding, as is the case with SLG. The different binding affinities of
      the membrane-anchored SRK and soluble eSRK or SLG will be significant for the
      specific perception of SP11 by SRK.

PMID- 17220206
TI  - Isolated tumour cells in pathological node-negative lymph nodes adversely affect
      prognosis in cancer of the oesophagus or oesophagogastric junction.
AB  - AIMS: To determine the prevalence of isolated tumour cells (ITC) in lymph nodes
      of patients with pathological node-negative (pN0) tumours and to assess their
      impact on disease-free and overall survival. METHODS: Paraffin embedded lymph
      nodes from oesophagogastrectomy specimens were examined immunohistochemically
      using monoclonal anti-cytokeratin antibody (MNF118). Clinical and pathological
      features were summarised and overall and relapse-free survival were estimated.
      RESULTS: Isolated tumour cells were detected in 12 of 146 patients (8%), and 24
      of 1694 (1%) lymph nodes. With a median follow-up time of 28 months (range 0-160
      months), both relapse-free and overall survival were significantly (p<0.05)
      associated with the presence of ITC in pN0 lymph nodes. There was no significant
      difference in the prevalence of ITC between patients who underwent multimodal
      therapy and those treated with surgery alone. CONCLUSIONS: ITC in pN0 lymph nodes
      may be less frequent than previously considered, but their presence is associated
      with poorer outcomes compared with true node negative disease.

PMID- 17220205
TI  - Endoscopic ultrasound guided fine needle aspiration of non-pancreatic lesions: an
      institutional experience.
AB  - BACKGROUND: Endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA)
      has proven to be an effective diagnostic modality for the detection and staging
      of pancreatic malignancies. In recent years EUS-FNA has also been used to
      diagnose lesions of non-pancreatic sites such as structures in close proximity to
      the gut wall within the mediastinum, abdomen, pelvis and retro-peritoneum. AIMS:
      To evaluate experience with EUS-FNA of non-pancreatic sites at a large university
      medical centre. METHODS: The study cohort included 234 patients who underwent EUS
      FNA of 246 lesions in non-pancreatic sites (122 peri-pancreatic and coeliac lymph
      nodes; 9 peri-pancreatic masses; other sites: mediastinum 12, gastric 25, liver
      27, oesophagus 17, duodenum/colon/rectum 15, retro-peritoneum 8, lung 7,
      miscellaneous 4). RESULTS: The cytology diagnoses were classified as non
      neoplastic/reactive in 82 (33%), atypical/suspicious for malignancy in 25 (10%),
      malignant in 86 (35%) and non-diagnostic in 53 (22%) cases. Surgical pathology
      follow-up was available in 75 (31%) cases. Excluding the non-diagnostic cases
      there were 7 false negative and 3 false positive cases. The sensitivity,
      specificity and positive predictive value of EUS-FNA in the diagnosis of lesions
      of non-pancreatic sites was 92%, 98% and 97%, respectively. CONCLUSIONS: EUS-FNA
      can be effectively used as a diagnostic modality in the diagnosis of lesions from
      non-pancreatic sites.

PMID- 17220207
TI  - Immunohistochemical study of nuclear factor-kappaB activity and interleukin-8
      abundance in oesophageal adenocarcinoma; a useful strategy for monitoring these
      biomarkers.
AB  - AIMS: To determine if immunohistochemistry (IHC) could be used to monitor nuclear
      factor-kappaB (NF-kappaB) activity in oesophageal adenocarcinoma and pre
      malignant (Barrett's) oesophageal tissues, relative to normal oesophageal mucosa.
      The pro-inflammatory cytokine interleukin-8 (IL-8), a transcriptional target of
      NF-kappaB, was also studied to better understand NF-kappaB functionality; its RNA
      and protein levels were assessed in oesophageal tissues. METHODS: IHC was
      employed using an antibody against the nuclear localisation sequence (NLS) of the
      p65 subunit as well as an antibody against IL-8. To assess NF-kappaB function,
      changes in gene expression of NF-kappaB controlled genes (IL-8 and I-kappaB) were
      also assessed in the histological sequence using real-time PCR. More global
      expression changes were also studied using membrane arrays. RESULTS: IHC was
      effective at monitoring overall NF-kappaB activity and IL-8 abundance. This
      method also allowed NF-kappaB activity and IL-8 abundance to be pinpointed in
      specific cell types. There were significant increases in nuclear NF-kappaB
      activity and IL-8 abundance across the histological series. Gene expression
      analysis also showed consistent up-regulation of IL-8, confirming the IHC data
      and showing enhanced transcriptional NF-kappaB activity. I-kappaB (another NF
      kappaB target) showed down-regulation in dysplastic and adenocarcinoma tissues.
      Down-regulation of I-kappaB gene expression may partly explain increased NF
      kappaB activity. CONCLUSION: IHC, using antibodies against the NLS of p65, may be
      useful in monitoring overall NF-kappaB activity in oesophageal tissues. As IHC is
      amenable to high-throughput screening (whereas traditional electrophoretic
      mobility shift assay methods are not), this may lead to the development of a
      better screening tool for early cancer risk.

PMID- 17220208
TI  - Pure red cell aplasia associated with type I autoimmune polyglandular syndrome
      successful response to treatment with mycophenolate mofetil: case report and
      review of literature.

PMID- 17220209
TI  - Borate transporter SLC4A11 mutations cause both Harboyan syndrome and non
      syndromic corneal endothelial dystrophy.
AB  - Harboyan syndrome, or corneal dystrophy and perceptive deafness (CDPD), consists
      of congenital corneal endothelial dystrophy and progressive perceptive deafness,
      and is transmitted as an autosomal recessive trait. CDPD and autosomal recessive,
      non-syndromic congenital hereditary endothelial corneal dystrophy (CHED2) both
      map at overlapping loci at 20p13, and mutations of SLC4A11 were reported recently
      in CHED2. A genotype study on six families with CDPD and on one family with
      either CHED or CDPD, from various ethnic backgrounds (in the seventh family,
      hearing loss could not be assessed because of the proband's young age), is
      reported here. Novel SLC4A11 mutations were found in all patients. Why some
      mutations cause hearing loss in addition to corneal dystrophy is presently
      unclear. These findings extend the implication of the SLC4A11 borate transporter
      beyond corneal dystrophy to perceptive deafness.

PMID- 17220210
TI  - Osteopoikilosis, short stature and mental retardation as key features of a new
      microdeletion syndrome on 12q14.
AB  - This report presents the detection of a heterozygous deletion at chromosome 12q14
      in three unrelated patients with a similar phenotype consisting of mild mental
      retardation, failure to thrive in infancy, proportionate short stature and
      osteopoikilosis as the most characteristic features. In each case, this
      interstitial deletion was found using molecular karyotyping. The deletion
      occurred as a de novo event and varied between 3.44 and 6 megabases (Mb) in size
      with a 3.44 Mb common deleted region. The deleted interval was not flanked by low
      copy repeats or segmental duplications. It contains 13 RefSeq genes, including
      LEMD3, which was previously shown to be the causal gene for osteopoikilosis. The
      observation of osteopoikilosis lesions should facilitate recognition of this new
      microdeletion syndrome among children with failure to thrive, short stature and
      learning disabilities.

PMID- 17220212
TI  - Integrin beta3 Leu33Pro polymorphism increases BRCA1-associated ovarian cancer
      risk.
AB  - Integrins are heterodimeric transmembrane glycoproteins that function as key
      adhesion and cell signalling receptors. A functional polymorphism in the integrin
      beta3 subunit encoded by the ITGB3 gene, Leu33Pro, has been shown to modify a
      variety of traits of beta3-expressing cells. To analyse the role of this
      functional polymorphism in modifying BRCA1-associated ovarian and breast cancer
      risks, a case-control study was performed among Polish BRCA1 mutation carriers
      including 319 breast cancer cases, 146 ovarian cancer cases and 290 controls
      unaffected by breast and ovarian cancer, in situ breast cancer or any other kind
      of cancer. Genotyping analysis was performed using PCR-based restriction fragment
      length polymorphism analysis. Odds ratios were calculated using univariate and
      multivariate logistic regression, taking into account a series of confounding
      variables, including the presence of related study subjects, that potentially
      could have biased any association. The results revealed that the ITGB3_Leu33Pro
      polymorphism was associated with a 2.5-fold increased risk of ovarian cancer,
      whereas no association with breast cancer risk was found. Thus, it appears that
      the ITGB3_Leu33Pro polymorphism may potentially increase the risk of ovarian
      cancer in Polish women with an inherited BRCA1 mutation.

PMID- 17220211
TI  - Environmental influence on the worldwide prevalence of a 776C->G variant in the
      transcobalamin gene (TCN2).
AB  - BACKGROUND: A 776C-->G variant (dbSNP ID: rs1801198) in the transcobalamin gene
      (TCN2; MIM# 275350) decreases the cellular and plasma concentration of
      transcobalamin and thereby influences the cellular availability of vitamin B(12).
      OBJECTIVE: To evaluate the worldwide prevalence of this variant and its
      association with homocysteine plasma level. METHODS: The study was performed in
      1433 apparently healthy subjects, including Afro-Americans and Afro-Africans and
      in 251 Afro-Africans participants with severe malaria. RESULTS: The frequencies
      of the 776G allele were the highest in China (0.607; 95% CI 0.554 to 0.659), low
      in West Africa (Benin and Togo, 0.178; 0.154 to 0.206), and intermediate in
      France (0.445; 0.408 to 0.481), Italy (0.352; 0.299 to 0.409), Morocco (0.370;
      0.300 to 0.447) and Mexico (0.374; 0.392 to 0.419). The 776G genotype was more
      frequent in Afro-Americans from New York (16.7; 8.4 to 30.7) and in Afro-African
      patients with severe malaria (6.0%; 95% CI 3.7 to 9.6) than in healthy Afro
      African volunteers (p = 0.0004 and p = 0.033, respectively), while no difference
      was observed for MTHFR 677TT and 677T alleles. A disequilibrium of TCN2 genotype
      distribution was recorded in patients with severe malaria, with a twofold higher
      GG genotype than expected (p = 0.010). An association between the TCN2
      polymorphism and homocysteine was observed only in Mexico and France, the two
      countries with the highest rate of low plasma concentration of vitamin B(12)
      (<100 pmol/l). CONCLUSION: Given the dramatic heterogeneity of the 776G allele
      frequency worldwide, this polymorphism may be prone to a selective pressure or
      confers an evolutionary advantage in confronting environmental factors, one of
      which is malaria.

PMID- 17220213
TI  - Phenotypic and population differences in the association between CILP and lumbar
      disc disease.
AB  - BACKGROUND: Lumbar disc disease (LDD) is one of the leading causes of disability
      in the working-age population. A functional single-nucleotide polymorphism (SNP),
      +1184T-->C, in exon 8 of the cartilage intermediate layer protein gene (CILP) was
      recently identified as a risk factor for LDD in the Japanese population (odds
      ratio (OR) 1.61, 95% CI 1.31 to 1.98), with implications for impaired
      transforming growth factorbeta1 signalling. AIM: To validate this finding in two
      different ethnic cohorts with LDD. METHODS: This SNP and flanking SNPs were
      analysed in 243 Finnish patients with symptoms of LDD and 259 controls, and in
      348 Chinese subjects with MRI-defined LDD and 343 controls. RESULTS AND
      CONCLUSION: The results showed no evidence of association in the Finnish (OR =
      1.35, 95% CI 0.97 to 1.87; p = 0.14) or the Chinese (OR = 1.05, 95% CI 0.77 to
      1.43; p = 0.71) samples, suggesting that cartilage intermediate layer protein
      gene is not a major risk factor for symptoms of LDD in Caucasians or in the
      general population that included individuals with or without symptoms.

PMID- 17220214
TI  - The human GIMAP5 gene has a common polyadenylation polymorphism increasing risk
      to systemic lupus erythematosus.
AB  - BACKGROUND: Several members of the GIMAP gene family have been suggested as being
      involved in different aspects of the immune system in different species.
      Recently, a mutation in the GIMAP5 gene was shown to cause lymphopenia in a rat
      model of autoimmune insulin-dependent diabetes. Thus it was hypothesised that
      genetic variation in GIMAP5 may be involved in susceptibility to other autoimmune
      disorders where lymphopenia is a key feature, such as systemic lupus
      erythematosus (SLE). MATERIAL AND METHODS: To investigate this, seven single
      nucleotide polymorphisms in GIMAP5 were analysed in five independent sets of
      family-based SLE collections, containing more than 2000 samples. RESULT: A
      significant increase in SLE risk associated with the most common GIMAP5 haplotype
      was found (OR 1.26, 95% CI 1.02 to 1.54, p = 0.0033). In families with probands
      diagnosed with trombocytopenia, the risk was increased (OR 2.11, 95% CI 1.09 to
      4.09, p = 0.0153). The risk haplotype bears a polymorphic polyadenylation signal
      which alters the 3' part of GIMAP5 mRNA by producing an inefficient
      polyadenylation signal. This results in higher proportion of non-terminated mRNA
      for homozygous individuals (p<0.005), a mechanism shown to be causal in
      thalassaemias. To further assess the functional effect of the polymorphic
      polyadenylation signal in the risk haplotype, monocytes were treated with several
      cytokines affecting apoptosis. All the apoptotic cytokines induced GIMAP5
      expression in two monocyte cell lines (1.5-6 times, p<0.0001 for all tests).
      CONCLUSION: Taken together, the data suggest the role of GIMAP5 in the
      pathogenesis of SLE.

PMID- 17220215
TI  - Genetic heterogeneity in Rubinstein-Taybi syndrome: delineation of the phenotype
      of the first patients carrying mutations in EP300.
AB  - BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a congenital disorder
      characterised by growth retardation, facial dysmorphisms, skeletal abnormalities
      and mental retardation. Broad thumbs and halluces are the hallmarks of the
      syndrome. RSTS is associated with chromosomal rearrangements and mutations in the
      CREB-binding protein gene (CREBBP), also termed CBP, encoding the CREB-binding
      protein. Recently, it was shown that mutations in EP300, coding for the p300
      protein, also cause RSTS. CBP and EP300 are highly homologous genes, which play
      important roles as global transcriptional coactivators. OBJECTIVE: To report the
      phenotype of the presently known patients with RSTS (n = 4) carrying germline
      mutations of EP300. RESULTS: The patients with EP300 mutations displayed the
      typical facial gestalt and malformation pattern compatible with the diagnosis of
      RSTS. However, three patients exhibited much milder skeletal findings on the
      hands and feet than typically observed in patients with RSTS. CONCLUSIONS: Part
      of the clinical variability in RSTS is explained by genetic heterogeneity. The
      diagnosis of RSTS must be expanded to include patients without broad thumbs or
      halluces.

PMID- 17220216
TI  - A hexanucleotide repeat upstream of eotaxin gene promoter is associated with
      asthma, serum total IgE and plasma eotaxin levels.
AB  - BACKGROUND: Eotaxin (CCL11) is a small protein produced in the lungs of patients
      with asthma, and is a potent chemoattractant for eosinophils. AIM: To elucidate
      the role of eotaxin in asthma by an association study of functional and novel
      eotaxin polymorphisms in case-control and family-based study designs. METHODS:
      Eotaxin +67G/A, -384A/G and -426C/T single-nucleotide polymorphisms and a
      hexanucleotide (GAAGGA)(n) repeat 10.9 kb upstream of the gene were genotyped in
      a cohort of age, sex and ethnically matched patients with asthma (n = 235) and
      healthy controls (n = 239), and also in a study population of 230 families with
      asthma recruited from north/northwest India. Total serum IgE (TsIgE) and plasma
      eotaxin levels were measured using ELISA. RESULTS: +67G/A polymorphism was found
      to be significantly associated with asthma in case-control (p = 0.009) and family
      based studies (p = 0.006). Its functional role, as it was correlated with plasma
      eotaxin levels (p = 0.006), was also demonstrated. Further, -384C/T single
      nucleotide polymorphism was found to be significantly associated with log(10)
      TsIgE (p = 0.016 in case-control and p = 0.018 in families) and eotaxin levels (p
      = 0.007). Most interestingly, for the first time, a highly significant
      association of the newly studied (GAAGGA)(n) hexanucleotide repeat with asthma (p
      = 3x10(-6)), log(10)TsIgE (p = 0.006) and eotaxin levels (p = 0.004) was
      observed. G_A_C_8 was also identified as an important risk haplotype associated
      with high TsIgE and plasma eotaxin levels. CONCLUSIONS: This study provides
      further evidence that eotaxin polymorphisms are associated with the development
      of asthma by regulating eotaxin levels and reinforces towards the scanning of
      other chemokine genes present at 17q21 locus for their association with asthma
      and related phenotypes.

PMID- 17220217
TI  - The orphan response regulator HP1021 of Helicobacter pylori regulates
      transcription of a gene cluster presumably involved in acetone metabolism.
AB  - Helicobacter pylori is a gastric pathogen for which no nonhuman reservoir is
      known. In accordance with the tight adaptation to its unique habitat, the human
      stomach, H. pylori is endowed with a very restricted repertoire of regulatory
      proteins. Nevertheless, the three complete two-component systems of H. pylori
      were shown to be involved in the regulation of important virulence traits like
      motility and acid resistance and in the control of metal homeostasis. HP1021 is
      an orphan response regulator with an atypical receiver domain whose inactivation
      has a considerable impact on the growth of H. pylori. Here we report the
      identification of HP1021-regulated genes by whole-genome transcriptional
      profiling. We show that the transcription of the essential housekeeping genes
      nifS and nifU, which are required for the assembly of Fe-S clusters, is activated
      by HP1021. Furthermore, we demonstrate that the expression of a gene cluster
      comprising open reading frames hp0690 to hp0693 and hp0695 to hp0697 which is
      probably involved in acetone metabolism is strongly upregulated by HP1021.
      Evidence is provided for a direct regulation of the hp0695-to-hp0697 operon by
      the binding of HP1021 to its promoter region.

PMID- 17220218
TI  - The rbmBCDEF gene cluster modulates development of rugose colony morphology and
      biofilm formation in Vibrio cholerae.
AB  - Vibrio cholerae, the causative agent of cholera, can undergo phenotypic variation
      generating rugose and smooth variants. The rugose variant forms corrugated
      colonies and well-developed biofilms and exhibits increased levels of resistance
      to several environmental stresses. Many of these phenotypes are mediated in part
      by increased expression of the vps genes, which are organized into vps-I and vps
      II coding regions, separated by an intergenic region. In this study, we generated
      in-frame deletions of the five genes located in the vps intergenic region, termed
      rbmB to -F (rugosity and biofilm structure modulators B to F) in the rugose
      genetic background, and characterized the mutants for rugose colony development
      and biofilm formation. Deletion of rbmB, which encodes a protein with low
      sequence similarity to polysaccharide hydrolases, resulted in an increase in
      colony corrugation and accumulation of exopolysaccharides relative to the rugose
      variant. RbmC and its homolog Bap1 are predicted to encode proteins with
      carbohydrate-binding domains. The colonies of the rbmC bap1 double deletion
      mutant and bap1 single deletion mutant exhibited a decrease in colony
      corrugation. Furthermore, the rbmC bap1 double deletion mutant was unable to form
      biofilms at the air-liquid interface after 2 days, while the biofilms formed on
      solid surfaces detached readily. Although the colony morphology of rbmDEF mutants
      was similar to that of the rugose variant, their biofilm structure and cell
      aggregation phenotypes were different than those of the rugose variant. Taken
      together, these results indicate that vps intergenic region genes encode proteins
      that are involved in biofilm matrix production and maintenance of biofilm
      structure and stability.

PMID- 17220219
TI  - Enhancement of the synthesis of RpoN, Cra, and H-NS by polyamines at the level of
      translation in Escherichia coli cultured with glucose and glutamate.
AB  - Proteins whose synthesis is enhanced by polyamines at the level of translation
      were identified in a polyamine-requiring mutant cultured in the presence of 0.1%
      glucose and 0.02% glutamate instead of 0.4% glucose as an energy source. Under
      these conditions, enhancement of cell growth by polyamines was almost the same as
      that in the presence of 0.4% glucose. It was found that synthesis of RpoN, Cra,
      and H-NS was enhanced by polyamines at the level of translation at the early
      logarithmic phase of growth (A(540) of 0.15). The effects of polyamines on
      synthesis of RpoN, H-NS, and Cra were due to the existence of unusual Shine
      Dalgarno sequences (RpoN and H-NS) and an inefficient GUG initiation codon (Cra)
      in their mRNAs. Thus, rpoN, cra, and hns genes were identified as new members of
      the polyamine modulon. Because most of the polyamine modulon genes thus far
      identified encode transcription factors (RpoS [sigma(38)], Cya, FecI [sigma(18)],
      Fis, RpoN [sigma(54)], Cra, and H-NS), DNA microarray analysis of mRNA expressed
      in cells was performed. At the early logarithmic phase of growth, a total of 97
      species of mRNAs that were up-regulated by polyamines more than twofold were
      under the control of seven polyamine modulon genes mentioned above.

PMID- 17220220
TI  - A novel two-component signaling system that activates transcription of an
      enterohemorrhagic Escherichia coli effector involved in remodeling of host actin.
AB  - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is responsible for worldwide
      outbreaks of bloody diarrhea, hemorrhagic colitis, and life-threatening hemolytic
      uremic syndrome. After colonizing the large intestine, EHEC forms attaching and
      effacing (AE) lesions on intestinal epithelial cells. These lesions cause
      destruction of the microvilli and elicit actin rearrangement to form pedestals
      that cup each bacterium individually. EHEC responds to a signal produced by the
      intestinal microbial flora, autoinducer-3 (AI-3), and the host hormones
      epinephrine and norepinephrine to activate transcription of the genes involved in
      AE lesion formation. These three signals, involved in interkingdom communication,
      are sensed by bacterial sensor kinases. Here we describe a novel two-component
      system, QseEF (quorum-sensing E. coli regulators E and F), which is part of the
      AI-3/epinephrine/norepinephrine signaling system. QseE is the sensor kinase and
      QseF the response regulator. The qseEF genes are cotranscribed, and transcription
      of qseEF is activated by epinephrine through the QseC sensor. A qseF mutant does
      not form AE lesions. QseF activates transcription of the gene encoding EspFu, an
      effector protein translocated to the host cell by the EHEC, which mimics a
      eukaryotic SH2/SH3 adapter protein to engender actin polymerization during
      pedestal formation. Expression of the espFu gene from a plasmid restored AE
      lesion formation to the qseF mutant, suggesting that lack of espFu expression in
      this mutant was responsible for the loss of pedestal formation. These findings
      suggest the QseEF is a two-component system involved in the regulation of AE
      lesion formation by EHEC.

PMID- 17220221
TI  - Mutagenesis of hetR reveals amino acids necessary for HetR function in the
      heterocystous cyanobacterium Anabaena sp. strain PCC 7120.
AB  - HetR is the master regulator of heterocyst differentiation in the filamentous
      cyanobacterium Anabaena sp. strain PCC 7120. Genetic selection was used to
      identify 33 amino acid substitutions in HetR that reduced the proportion of cells
      undergoing heterocyst differentiation to less than 2%. Conservative substitutions
      in the wild-type HetR protein revealed three mutations that dramatically reduced
      the amount of heterocyst differentiation when the mutant allele was present in
      place of the wild-type allele on a replicating plasmid in a mutant lacking hetR
      on the chromosome. An H69Y substitution resulted in heterocyst formation among
      less than 0.1% of cells, and D17E and G36A substitutions resulted in a Het-
      phenotype, compared to heterocyst formation among approximately 25% of cells with
      the wild-type hetR under the same conditions. The D17E substitution prevented DNA
      binding activity exhibited by wild-type HetR in mobility shift assays, whereas
      G36A and H69Y substitutions had no affect on DNA binding. D17E, G36A, and H69Y
      substitutions also resulted in higher levels of the corresponding HetR protein
      than of the wild-type protein when each was expressed from an inducible promoter
      in a hetR deletion strain, suggesting an effect on HetR protein turnover.
      Surprisingly, C48A and S152A substitutions, which were previously reported to
      result in a Het- phenotype, were found to have no effect on heterocyst
      differentiation or patterning when the corresponding mutations were introduced
      into an otherwise wild-type genetic background in Anabaena sp. strain PCC 7120.
      The clustering of mutations that satisfied the positive selection near the amino
      terminus suggests an important role for this part of the protein in HetR
      function.

PMID- 17220222
TI  - Inferring a population structure for Staphylococcus epidermidis from multilocus
      sequence typing data.
AB  - Despite its importance as a human pathogen, information on population structure
      and global epidemiology of Staphylococcus epidermidis is scarce and the relative
      importance of the mechanisms contributing to clonal diversification is unknown.
      In this study, we addressed these issues by analyzing a representative collection
      of S. epidermidis isolates from diverse geographic and clinical origins using
      multilocus sequence typing (MLST). Additionally, we characterized the mobile
      element (SCCmec) carrying the genetic determinant of methicillin resistance. The
      217 S. epidermidis isolates from our collection were split by MLST into 74 types,
      suggesting a high level of genetic diversity. Analysis of MLST data using the
      eBURST algorithm revealed the existence of nine epidemic clonal lineages that
      were disseminated worldwide. One single clonal lineage (clonal complex 2)
      comprised 74% of the isolates, whereas the remaining isolates were clustered into
      8 minor clonal lineages and 13 singletons. According to our evolutionary model,
      SCCmec was acquired at least 56 times by S. epidermidis. Although geographic
      dissemination of S. epidermidis strains and the value of the index of association
      between the alleles, 0.2898 (P < 0.05), support the clonality of S. epidermidis
      species, examination of the sequence changes at MLST loci during clonal
      diversification showed that recombination gives rise to new alleles approximately
      twice as frequently as point mutations. We suggest that S. epidermidis has a
      population with an epidemic structure, in which nine clones have emerged upon a
      recombining background and evolved quickly through frequent transfer of genetic
      mobile elements, including SCCmec.

PMID- 17220223
TI  - The sugar phosphotransferase system of Vibrio fischeri inhibits both motility and
      bioluminescence.
AB  - Magnesium-dependent induction of Vibrio fischeri flagellar (Mif) biogenesis
      depends upon two diguanylate cyclases, suggesting an inhibitory role for cyclic
      di-GMP. Here, we report that cells defective for the sugar phosphotransferase
      system (PTS) exhibited a magnesium-independent phenotype similar to that of
      mutants of the Mif pathway. Unlike Mif mutants, PTS mutants also were
      hyperbioluminescent.

PMID- 17220224
TI  - Multiple roles of biosurfactants in structural biofilm development by Pseudomonas
      aeruginosa.
AB  - Recent studies have indicated that biosurfactants produced by Pseudomonas
      aeruginosa play a role both in maintaining channels between multicellular
      structures in biofilms and in dispersal of cells from biofilms. Through the use
      of flow cell technology and enhanced confocal laser scanning microscopy, we have
      obtained results which suggest that the biosurfactants produced by P. aeruginosa
      play additional roles in structural biofilm development. We present genetic
      evidence that during biofilm development by P. aeruginosa, biosurfactants promote
      microcolony formation in the initial phase and facilitate migration-dependent
      structural development in the later phase. P. aeruginosa rhlA mutants, deficient
      in synthesis of biosurfactants, were not capable of forming microcolonies in the
      initial phase of biofilm formation. Experiments involving two-color-coded mixed
      strain biofilms showed that P. aeruginosa rhlA mutants were defective in
      migration-dependent development of mushroom-shaped multicellular structures in
      the later phase of biofilm formation. Experiments involving three-color-coded
      mixed-strain P. aeruginosa biofilms demonstrated that the wild-type and rhlA and
      pilA mutant strains formed distinct subpopulations on top of each other dependent
      on their ability to migrate and produce biosurfactants.

PMID- 17220225
TI  - An unusual response regulator influences sporulation at early and late stages in
      Streptomyces coelicolor.
AB  - WhiI, a regulator required for efficient sporulation septation in the aerial
      mycelium of Streptomyces coelicolor, resembles response regulators of bacterial
      two-component systems but lacks some conserved features of typical
      phosphorylation pockets. Four amino acids of the abnormal "phosphorylation
      pocket" were changed by site-directed mutagenesis. Unlike whiI null mutations,
      these point mutations did not interfere with sporulation septation but had
      various effects on spore maturation. Transcriptome analysis was used to compare
      gene expression in the wild-type strain, a D27A mutant (pale gray spores), a D69E
      mutant (wild-type spores), and a null mutant (white aerial mycelium, no spores)
      (a new variant of PCR targeting was used to introduce the point mutations into
      the chromosomal copy of whiI). The results revealed 45 genes that were affected
      by the deletion of whiI. Many of these showed increased expression in the wild
      type at the time when aerial growth and development were taking place. About half
      of them showed reduced expression in the null mutant, and about half showed
      increased expression. Some, but not all, of these 45 genes were also affected by
      the D27A mutation, and a few were affected by the D69E mutation. The results were
      consistent with a model in which WhiI acts differently at sequential stages of
      development. Consideration of the functions of whiI-influenced genes provides
      some insights into the physiology of aerial hyphae. Mutation of seven whiI
      influenced genes revealed that three of them play roles in spore maturation.

PMID- 17220226
TI  - Ligand-controlled proteolysis of the Escherichia coli transcriptional regulator
      ZntR.
AB  - Proteases play a crucial role in remodeling the bacterial proteome in response to
      changes in cellular environment. Escherichia coli ZntR, a zinc-responsive
      transcriptional regulator, was identified by proteomic experiments as a likely
      ClpXP substrate, suggesting that protein turnover may play a role in regulation
      of zinc homeostasis. When intracellular zinc levels are high, ZntR activates
      expression of ZntA, an ATPase essential for zinc export. We find that ZntR is
      degraded in vivo in a manner dependent on both the ClpXP and Lon proteases.
      However, ZntR degradation decreases in the presence of high zinc concentrations,
      the level of ZntR rises, and transcription of the zntA exporter is increased.
      Mutagenesis experiments reveal that zinc binding does not appear to be solely
      responsible for the zinc-induced protection from proteolysis. Therefore, we
      tested whether DNA binding was important in the zinc-induced stabilization of
      ZntR by mutagenesis of the DNA binding helices. Replacement of a conserved
      arginine (R19A) in the DNA binding domain both enhances ZntR degradation and
      abolishes zinc-induced transcriptional activation of zntA. Biochemical and
      physical analysis of ZntR(R19A) demonstrates that it is structurally similar to,
      and binds zinc as well as does, the wild-type protein but is severely defective
      in binding DNA. Thus, we conclude that two different ligands-zinc and DNA
      function together to increase ZntR stability and that ligand-controlled
      proteolysis of ZntR plays an important role in fine-tuning zinc homeostasis in
      bacteria.

PMID- 17220227
TI  - RR06 activates transcription of spr1996 and cbpA in Streptococcus pneumoniae.
AB  - Streptococcus pneumoniae colonizes at the nasopharynx of humans and is able to
      disseminate and cause various infections. The hallmark of pneumococcal disease is
      rapid bacterial replication in different tissue sites leading to intense
      inflammation. The genetic basis of pneumococcal adaptation to different host
      niches remains sketchy. In this study, we investigated the regulatory effect of
      RR06, a response regulator protein, on gene expression of S. pneumoniae.
      Microarray and Northern blot analyses showed that RR06 is specifically required
      for transcription of spr1996 and cbpA. While the function of Spr1996 is unknown,
      CbpA has been well characterized as a surface-exposed protective antigen and a
      virulence factor of S. pneumoniae. A recombinant form of RR06 was able to bind to
      a 19-bp conserved sequence shared by the spr1996 and cbpA promoter regions.
      Furthermore, inactivation of rr06 resulted in loss of CbpA expression as detected
      by antibody staining and bacterial adhesion. CbpA expression was restored in
      trans by the intact rr06 gene. However, a mutant, RR06(D51A), with a point
      mutation in the aspartate residue at position 51 (a predicted major
      phosphorylation site) of RR06, completely abolished the CbpA expression,
      suggesting that RR06 phosphorylation is required for transcriptional activation
      of spr1996 and cbpA. Finally, inactivation of rr06 in additional pneumococcal
      strains also led to the loss of CbpA expression. These data implicate that RR06
      activates the expression of spr1996 and cbpA in many other pneumococcal strains.

PMID- 17220228
TI  - The HP0165-HP0166 two-component system (ArsRS) regulates acid-induced expression
      of HP1186 alpha-carbonic anhydrase in Helicobacter pylori by activating the pH
      dependent promoter.
AB  - The periplasmic alpha-carbonic anhydrase of Helicobacter pylori is essential for
      buffering the periplasm at acidic pH. This enzyme is an integral component of the
      acid acclimation response that allows this neutralophile to colonize the stomach.
      Transcription of the HP1186 alpha-carbonic anhydrase gene is upregulated in
      response to low environmental pH. A binding site for the HP0166 response
      regulator (ArsR) has been identified in the promoter region of the HP1186 gene.
      To investigate the mechanism that regulates the expression of HP1186 in response
      to low pH and the role of the HP0165-HP0166 two-component system (ArsRS) in this
      acid-inducible regulation, Northern blot analysis was performed with RNAs
      isolated from two different wild-type H. pylori strains (26695 and 43504) and
      mutants with HP0165 histidine kinase (ArsS) deletions, after exposure to either
      neutral pH or low pH (pH 4.5). ArsS-dependent upregulation of HP1186 alpha
      carbonic anhydrase in response to low pH was found in both strains. Western blot
      analysis of H. pylori membrane proteins confirmed the regulatory role of ArsS in
      HP1186 expression in response to low pH. Analysis of the HP1186 promoter region
      revealed two possible transcription start points (TSP1 and TSP2) located 43 and
      11 bp 5' of the ATG start codon, respectively, suggesting that there are two
      promoters transcribing the HP1186 gene. Quantitative primer extension analysis
      showed that the promoter from TSP1 (43 bp 5' of the ATG start codon) is a pH
      dependent promoter and is regulated by ArsRS in combating environmental acidity,
      whereas the promoter from TSP2 may be responsible for control of the basal
      transcription of HP1186 alpha-carbonic anhydrase.

PMID- 17220229
TI  - FNR is a global regulator of virulence and anaerobic metabolism in Salmonella
      enterica serovar Typhimurium (ATCC 14028s).
AB  - Salmonella enterica serovar Typhimurium must successfully transition the broad
      fluctuations in oxygen concentrations encountered in the host. In Escherichia
      coli, FNR is one of the main regulatory proteins involved in O2 sensing. To
      assess the role of FNR in serovar Typhimurium, we constructed an isogenic fnr
      mutant in the virulent wild-type strain (ATCC 14028s) and compared their
      transcriptional profiles and pathogenicities in mice. Here, we report that, under
      anaerobic conditions, 311 genes (6.80% of the genome) are regulated directly or
      indirectly by FNR; of these, 87 genes (28%) are poorly characterized. Regulation
      by FNR in serovar Typhimurium is similar to, but distinct from, that in E. coli.
      Thus, genes/operons involved in aerobic metabolism, NO. detoxification, flagellar
      biosynthesis, motility, chemotaxis, and anaerobic carbon utilization are
      regulated by FNR in a fashion similar to that in E. coli. However, genes/operons
      existing in E. coli but regulated by FNR only in serovar Typhimurium include
      those coding for ethanolamine utilization, a universal stress protein, a ferritin
      like protein, and a phosphotransacetylase. Interestingly, Salmonella-specific
      genes/operons regulated by FNR include numerous virulence genes within Salmonella
      pathogenicity island 1 (SPI-1), newly identified flagellar genes (mcpAC, cheV),
      and the virulence operon (srfABC). Furthermore, the role of FNR as a positive
      regulator of motility, flagellar biosynthesis, and pathogenesis was confirmed by
      showing that the mutant is nonmotile, lacks flagella, is attenuated in mice, and
      does not survive inside macrophages. The inability of the mutant to survive
      inside macrophages is likely due to its sensitivity to the reactive oxygen
      species generated by NADPH phagocyte oxidase.

PMID- 17220230
TI  - A novel lipolytic enzyme, YcsK (LipC), located in the spore coat of Bacillus
      subtilis, is involved in spore germination.
AB  - The predicted amino acid sequence of Bacillus subtilis ycsK exhibits similarity
      to the GDSL family of lipolytic enzymes. Northern blot analysis showed that ycsK
      mRNA was first detected from 4 h after the onset of sporulation and that
      transcription of ycsK was dependent on SigK and GerE. The fluorescence of the
      YcsK-green fluorescent protein fusion protein produced in sporulating cells was
      detectable in the mother cell but not in the forespore compartment under
      fluorescence microscopy, and the fusion protein was localized around the
      developing spores dependent on CotE, SafA, and SpoVID. Inactivation of the ycsK
      gene by insertion of an erythromycin resistance gene did not affect vegetative
      growth or spore resistance to heat, lysozyme, or chloroform. The germination of
      ycsK spores in a mixture of L-asparagine, D-glucose, D-fructose, and potassium
      chloride and LB medium was also the same as that of wild-type spores, but the
      mutant spores were defective in L-alanine-stimulated germination. In addition,
      zymogram analysis demonstrated that the YcsK protein heterologously expressed in
      Escherichia coli showed lipolytic activity. We therefore propose that ycsK should
      be renamed lipC. This is the first study of a bacterial spore germination-related
      lipase.

PMID- 17220231
TI  - A single residue change in Vibrio harveyi hemolysin results in the loss of
      phospholipase and hemolytic activities and pathogenicity for turbot (Scophthalmus
      maximus).
AB  - Vibrio harveyi hemolysin, an important virulence determinant in fish
      pathogenesis, was further characterized, and the enzyme was identified as a
      phospholipase B by gas chromatography. Site-directed mutagenesis revealed that a
      specific residue, Ser153, was critical for its enzymatic activity and for its
      virulence in fish.

PMID- 17220232
TI  - Interrelationships between colonies, biofilms, and planktonic cells of
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is a gram-negative bacterium and an opportunistic human
      pathogen that causes chronic infections in immunocompromised individuals. These
      infections are hard to treat, partly due to the high intrinsic resistance of the
      bacterium to clinically used antibiotics and partly due to the formation of
      antibiotic-tolerant biofilms. The three most common ways of growing bacteria in
      vitro are as planktonic cultures, colonies on agar plates, and biofilms in
      continuous-flow systems. Biofilms are known to express genes different from those
      of planktonic cells, and biofilm cells are generally believed to closely resemble
      planktonic cells in stationary phase. However, few, if any, studies have examined
      global gene expression in colonies. We used a proteomic approach to investigate
      the interrelationships between planktonic cells, colonies, and biofilms under
      comparable conditions. Our results show that protein profiles in colonies
      resemble those of planktonic cells. Furthermore, contrary to what has been
      reported previously, the protein profiles of biofilms were found to more closely
      resemble those of exponentially growing planktonic cells than those of planktonic
      cells in the stationary phase. These findings raise some intriguing questions
      about the true nature of biofilms.

PMID- 17220233
TI  - Mutagenesis and repair in Bacillus anthracis: the effect of mutators.
AB  - We have generated mutator strains of Bacillus anthracis Sterne by using directed
      gene knockouts to investigate the effect of deleting genes involved in mismatch
      repair, oxidative repair, and maintaining triphosphate pools. The single-knockout
      strains are deleted for mutS, mutY, mutM, or ndk. We also made double-knockout
      strains that are mutS ndk or mutY mutM. We have measured the levels of mutations
      in the rpoB gene that lead to the Rif(r) phenotype and have examined the
      mutational specificity. In addition, we examined the mutational specificity of
      two mutagens, 5-azacytidine and N-methyl-N'-nitro-N-nitroso-guanidine. The mutY
      and mutM single knockouts are weak mutators by themselves, but the combination of
      mutY mutM results in very high mutation rates, all due to G:C --> T:A
      transversions. The situation parallels that seen in Escherichia coli. Also, mutS
      knockouts are strong mutators and even stronger in the presence of a deletion of
      ndk. The number of sites in rpoB that can result in the Rif(r) phenotype by
      single-base substitution is more limited than in certain other bacteria, such as
      E. coli and Deinococcus radiodurans, although the average mutation rate per
      mutational site is roughly comparable. Hotspots at sites with virtually identical
      surrounding sequences are organism specific.

PMID- 17220234
TI  - Glucuronidation of antiallergic drug, Tranilast: identification of human UDP
      glucuronosyltransferase isoforms and effect of its phase I metabolite.
AB  - Tranilast is an oral antiallergic agent widely used in Japan. Recently, in
      Western populations, hyperbilirubinemia induced by tranilast was suspected during
      clinical trials. Tranilast has been reported to be mainly metabolized to a
      glucuronide and a phase I metabolite, 4-demethyltranilast (N-3). In the present
      study, we investigated the in vitro metabolism of tranilast in human liver and
      jejunum microsomes and recombinant UDP-glucuronosyltransferases (UGTs). The
      glucuronidation of tranilast was clarified to be mainly catalyzed by UGT1A1 in
      human liver and intestine. The K(m) values of tranilast glucuronosyltransferase
      activity were 51.5, 50.6, and 38.0 microM in human liver microsomes, human
      jejunum microsomes, and recombinant UGT1A1, respectively. The V(max) values were
      10.4, 42.9, and 19.7 pmol/min/mg protein in human liver microsomes, human jejunum
      microsomes, and recombinant UGT1A1, respectively. When the intrinsic clearance
      was calculated using the in vitro kinetic parameters, microsomal protein content,
      and weight of tissues, tranilast glucuronosyltransferase activity was 2.5-fold
      higher in liver than in intestine. Tranilast glucuronosyltransferase activity was
      strongly inhibited by bilirubin, a typical UGT1A1 substrate, and N-3, indicating
      that the phase I metabolite could affect the tranilast glucuronosyltransferase
      activity. In the case of N-3 formation, the K(m) and V(max) values were 37.1
      microM and 27.6 pmol/min/mg protein in human liver microsomes. The bilirubin
      glucuronosyltransferase activity was strongly inhibited by both tranilast and N
      3, suggesting that tranilast-induced hyperbilirubinemia would be responsible for
      the inhibition by tranilast and N-3 of the bilirubin glucuronosyltransferase
      activity, as would the UGT1A1 genotype.

PMID- 17220235
TI  - Formation and uptake of arylhydroxylamine-haptenated proteins in human dendritic
      cells.
AB  - Bioactivation of sulfonamides and the subsequent formation of haptenated proteins
      is believed to be a critical step in the development of hypersensitivity
      reactions to these drugs. Numerous lines of evidence suggest that the presence of
      such adducts in dendritic cells (DCs) migrating to draining lymph nodes is
      essential for the development of cutaneous reactions to xenobiotics. Our
      objective was to determine the ability of human DCs to form drug-protein covalent
      adducts when exposed to sulfamethoxazole (SMX), dapsone (DDS), or their
      arylhydroxylamine metabolites [sulfamethoxazole hydroxylamine (S-NOH) and dapsone
      hydroxylamine (D-NOH)] and to take up preformed adduct. Naive and immature CD34+
      KG-1 cells were incubated with SMX, DDS, or metabolites. Formation of haptenated
      proteins was probed using confocal microscopy and ELISA. Cells were also
      incubated with preformed adduct (drug-bovine serum albumin conjugate), and uptake
      was determined using confocal microscopy. Both naive and immature KG-1 cells were
      able to bioactivate DDS, forming drug-protein adducts, whereas cells showed very
      little protein haptenation when exposed to SMX. Exposure to S-NOH or D-NOH
      resulted in protein haptenation in both cell types. Both immature and naive KG-1
      cells were able to take up preformed haptenated proteins. Thus, DCs may acquire
      haptenated proteins associated with drugs via intracellular bioactivation, uptake
      of reactive metabolites, or uptake of adduct formed and released by adjacent
      cells (e.g., keratinocytes).

PMID- 17220236
TI  - Zonal gene expression in mouse liver resembles expression patterns of Ha-ras and
      beta-catenin mutated hepatomas.
AB  - Hepatocytes of the periportal and perivenous zones of the liver lobule differ in
      their levels and activities of various enzymes and other proteins. We have
      recently suggested that beta-catenin- and Ras-dependent signaling pathways play
      an important role in the regulation of perivenous and periportal gene expression
      profiles. This hypothesis was primarily based on similarities in zonal
      differences in gene expression of hepatocytes from normal liver with gene
      expression patterns of liver tumors: several proteins and mRNAs preferentially
      expressed in periportal hepatocytes were often overexpressed in Ha-ras mutated
      mouse liver tumors, whereas perivenous markers were overexpressed in Ctnnb1
      (encoding beta-catenin) mutated tumors. We have now extended this work by use of
      data from two previously conducted microarray analyses aimed to analyze 1) global
      gene expression patterns of Ha-ras and Ctnnb1 mutated mouse liver tumors and 2)
      transcriptome differences between periportal and perivenous mouse hepatocytes. By
      comparison of the datasets, 134 genes or expressed sequences were identified that
      were present in both datasets. Gene expression patterns in perivenous hepatocytes
      and Ctnnb1 mutated hepatoma cells were strongly correlated: 96.5% of the genes
      present in both datasets were regulated in the same direction. In analogy,
      expression of 74.1% of the genes deregulated in Ha-ras mutated tumors was
      correlated with the respective expression patterns in periportal hepatocytes.
      These findings favor the hypothesis that gene expression patterns in periportal
      and perivenous hepatocytes are regulated, at least in part, by Ras- and beta
      catenin-dependent signaling pathways.

PMID- 17220237
TI  - Identification and functional characterization of genetic variants of human
      organic cation transporters in a Korean population.
AB  - Genetic variants of three human organic cation transporter genes (hOCTs) were
      extensively explored in a Korean population. The functional changes of hOCT2
      variants were evaluated in vitro, and those genetic polymorphisms of hOCTs were
      compared among different ethnic populations. From direct DNA sequencing, 7 of 13
      coding variants were nonsynonymous single-nucleotide polymorphisms (SNPs),
      including four variants from hOCT1 (F160L, P283L, P341L, and M408V) and three
      from hOCT2 (T199I, T201M, and A270S), whereas 6 were synonymous SNPs. The linkage
      disequilibrium analysis presented for three independent LD blocks for each hOCT
      gene showed no significant linkage among all three hOCT genes. The transporter
      activities of MDCK cells that overexpress the hOCT2-T199I, -T201M, and -A270S
      variants showed significantly decreased uptake of [(3)H]methyl-4-phenylpyridinium
      acetate (MPP(+)) or [(14)C]tetraethylammonium compared with those cells that
      overexpress wild-type hOCT2, and the estimated kinetic parameters of these
      variants for [(3)H]MPP(+) uptake in oocytes showed a 2- to 5-fold increase in
      K(m) values and a 10- to 20-fold decrease in V(max) values. The allele
      frequencies of the five functional variants hOCT1-P283L, -P341L, and hOCT2-T199I,
      -T201M, and -A270S were 1.3, 17, 0.7, 0.7, and 11%, respectively, in a Korean
      population; the frequency distributions of these variants were not significantly
      different from those of Chinese and Vietnamese populations. These findings
      suggest that genetic variants of hOCTs are not linked among three genes in a
      Korean population, and several of the hOCT genetic variants cause decreased
      transport activity in vitro compared with the wild type, although the clinical
      relevance of these variants remains to be evaluated.

PMID- 17220238
TI  - Regional distribution of solute carrier mRNA expression along the human
      intestinal tract.
AB  - Intestinal absorption of drugs, nutrients, and other compounds is mediated by
      uptake transporters expressed at the apical enterocyte membrane. These compounds
      are returned to the intestinal lumen or released into portal circulation by
      intestinal efflux transporters expressed at apical or basolateral membranes,
      respectively. One important transporter superfamily, multiple members of which
      are intestinally expressed, are the solute carriers (SLCs). SLC expression levels
      may determine the pharmacokinetics of drugs that are substrates of these
      transporters. In this study we characterize the distribution of 15 human SLC
      transporter mRNAs in histologically normal biopsies from five regions of the
      intestine of 10 patients. The mRNA expression levels of CNT1, CNT2, apical sodium
      dependent bile acid transporter (ABST), serotonin transporter (SERT), PEPT1, and
      OCTN2 exhibit marked differences between different regions of the intestine: the
      first five are predominantly expressed in the small intestine, whereas OCTN2
      exhibits strongest expression in the colon. Two transporter mRNAs studied (OCTN1,
      OATP2B1) are expressed at similar levels in all gut sections. In addition, ENT2
      mRNA is present at low levels across the colon, but not in the small intestine.
      The other six SLC mRNAs studied are not expressed in the intestine. Quantitative
      knowledge of transporter expression levels in different regions of the human
      gastrointestinal tract could be useful for designing intestinal delivery
      strategies for orally administered drugs. Furthermore, changes in transporter
      expression that occur in pathological states, such as inflammatory bowel disease,
      can now be defined more precisely by comparison with the expression levels
      measured in healthy individuals.

PMID- 17220239
TI  - Metabolism and excretion of the dipeptidyl peptidase 4 inhibitor [14C]sitagliptin
      in humans.
AB  - The metabolism and excretion of [(14)C]sitagliptin, an orally active, potent and
      selective dipeptidyl peptidase 4 inhibitor, were investigated in humans after a
      single oral dose of 83 mg/193 muCi. Urine, feces, and plasma were collected at
      regular intervals for up to 7 days. The primary route of excretion of
      radioactivity was via the kidneys, with a mean value of 87% of the administered
      dose recovered in urine. Mean fecal excretion was 13% of the administered dose.
      Parent drug was the major radioactive component in plasma, urine, and feces, with
      only 16% of the dose excreted as metabolites (13% in urine and 3% in feces),
      indicating that sitagliptin was eliminated primarily by renal excretion.
      Approximately 74% of plasma AUC of total radioactivity was accounted for by
      parent drug. Six metabolites were detected at trace levels, each representing <1
      to 7% of the radioactivity in plasma. These metabolites were the N-sulfate and N
      carbamoyl glucuronic acid conjugates of parent drug, a mixture of hydroxylated
      derivatives, an ether glucuronide of a hydroxylated metabolite, and two
      metabolites formed by oxidative desaturation of the piperazine ring followed by
      cyclization. These metabolites were detected also in urine, at low levels.
      Metabolite profiles in feces were similar to those in urine and plasma, except
      that the glucuronides were not detected in feces. CYP3A4 was the major cytochrome
      P450 isozyme responsible for the limited oxidative metabolism of sitagliptin,
      with some minor contribution from CYP2C8.

PMID- 17220240
TI  - Characterization of two cyclic metabolites of sitagliptin.
AB  - Two novel metabolites of the dipeptidyl peptidase inhibitor sitagliptin (MK-0431,
      (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)
      yl]-1-(2,4,5-trifluorophenyl)-butan-2-amine), were identified after purification
      from dog urine. The metabolites (referred to as M2 and M5) were characterized by
      hydrogen/deuterium exchange tandem mass spectrometry and NMR spectroscopy nuclear
      Overhauser effect experiments as the cis and trans stereoisomers formed by
      cyclization of the primary amino group with the alpha carbon of the piperazine
      ring, following oxidative desaturation.

PMID- 17220241
TI  - Disposition of the dipeptidyl peptidase 4 inhibitor sitagliptin in rats and dogs.
AB  - The pharmacokinetics, metabolism, and excretion of sitagliptin [MK-0431; (2R)-4
      oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1
      (2,4,5-trifluorophenyl)butan-2-amine], a potent dipeptidyl peptidase 4 inhibitor,
      were evaluated in male Sprague-Dawley rats and beagle dogs. The plasma clearance
      and volume of distribution of sitagliptin were higher in rats (40-48 ml/min/kg, 7
      9 l/kg) than in dogs ( approximately 9 ml/min/kg, approximately 3 l/kg), and its
      half-life was shorter in rats, approximately 2 h compared with approximately 4 h
      in dogs. Sitagliptin was absorbed rapidly after oral administration of a solution
      of the phosphate salt. The absolute oral bioavailability was high, and the
      pharmacokinetics were fairly dose-proportional. After administration of
      [(14)C]sitagliptin, parent drug was the major radioactive component in rat and
      dog plasma, urine, bile, and feces. Sitagliptin was eliminated primarily by renal
      excretion of parent drug; biliary excretion was an important pathway in rats,
      whereas metabolism was minimal in both species in vitro and in vivo.
      Approximately 10 to 16% of the radiolabeled dose was recovered in the rat and dog
      excreta as phase I and II metabolites, which were formed by N-sulfation, N
      carbamoyl glucuronidation, hydroxylation of the triazolopiperazine ring, and
      oxidative desaturation of the piperazine ring followed by cyclization via the
      primary amine. The renal clearance of unbound drug in rats, 32 to 39 ml/min/kg,
      far exceeded the glomerular filtration rate, indicative of active renal
      elimination of parent drug.

PMID- 17220243
TI  - Metabolism and excretion of RWJ-333369 [1,2-ethanediol, 1-(2-chlorophenyl)-, 2
      carbamate, (S)-] in mice, rats, rabbits, and dogs.
AB  - The in vivo metabolism and excretion of RWJ-333369 [1,2-ethanediol, 1-(2
      chlorophenyl)-, 2-carbamate, (S)-], a novel neuromodulator, were investigated in
      mice, rats, rabbits, and dogs after oral administration of (14)C-RWJ-333369.
      Plasma, urine, and feces samples were collected, assayed for radioactivity, and
      profiled for metabolites. In almost all species, the administered radioactive
      dose was predominantly excreted in urine (>85%) with less than 10% in feces.
      Excretion of radioactivity was rapid and nearly complete at 96 h after dosing in
      all species. Unchanged drug excreted in urine was minimal (<2.3% of the
      administered dose) in all species. The primary metabolic pathways were O
      glucuronidation (rabbit > mouse > dog > rat) of RWJ-333369 and hydrolysis of the
      carbamate ester followed by oxidation to 2-chloromandelic acid. The latter
      metabolite was subsequently metabolized in parallel to 2-chlorophenylglycine and
      2-chlorobenzoic acid (combined hydrolytic and oxidative pathways: rat > dog >
      mouse > rabbit). Other metabolic pathways present in all species included chiral
      inversion in combination with O-glucuronidation and sulfate conjugation (directly
      and/or following hydroxylation of RWJ-333369). Species-specific pathways,
      including N-acetylation of 2-chlorophenylglycine (mice, rats, and dogs) and arene
      oxidation followed by glutathione conjugation of RWJ-333369 (mice and rats), were
      more predominant in rodents than in other species. Consistent with human
      metabolism, multiple metabolic pathways and renal excretion were mainly involved
      in the elimination of RWJ-333369 and its metabolites in animal species. Unchanged
      drug was the major plasma circulating drug-related substance in the preclinical
      species and humans.

PMID- 17220242
TI  - Detection of human CYP2C8, CYP2C9, and CYP2J2 in cardiovascular tissues.
AB  - The cytochrome P450 (P450) enzymes CYP2C8, CYP2C9, and CYP2J2 metabolize
      arachidonic acid to epoxyeicosatrienoic acids, which are known to be vital in
      regulation of vascular tone and cardiovascular homeostasis. Because there is
      limited information regarding the relative expression of these P450 enzymes in
      cardiovascular tissues, this study examined the expression of CYP2C8, CYP2C9, and
      CYP2J2 mRNA and protein in human heart, aorta, and coronary artery samples by
      real-time polymerase chain reaction, immunoblotting, and immunohistochemistry.
      CYP2J2 and CYP2C9 mRNA levels were highly variable in human hearts, whereas
      CYP2C8 mRNA was present in lower abundance. CYP2J2 mRNA was approximately 10(3)
      times higher than CYP2C9 or CYP2C8 in human heart. However, CYP2C9 mRNA was more
      abundant than CYP2J2 or CYP2C8 in one ischemic heart. In human aorta, mean CYP2C9
      mRNA levels were approximately 50 times higher than that of CYP2J2 and 5-fold
      higher than that of CYP2C8. In human coronary artery, mean values for CYP2C9 mRNA
      were approximately 2-fold higher than that of CYP2J2 mRNA and 6-fold higher than
      that of CYP2C8 mRNA. Immunoblotting results show relatively high levels of CYP2J2
      and CYP2C8 protein in human hearts, which was confirmed by immunohistochemistry.
      CYP2C9 protein was also detected at high levels in one ischemic heart by
      immunoblotting. CYP2C9 was present at higher levels than CYPJ2 in aorta and
      coronary artery, whereas CYP2C8 protein was below the limits of detection. The
      expression of CYP2J2 and CYP2C8 in human heart, and CYPC9 and CYP2J2 in aorta and
      coronary artery is consistent with a physiological role for these enzymes in
      these tissues.

PMID- 17220244
TI  - Interactions of cyclosporin a with breast cancer resistance protein.
AB  - The objective of this study was to investigate whether cyclosporin A (CsA) is a
      modulator for breast cancer resistance protein (BCRP). The interactions between
      CsA and BCRP were evaluated by using both membrane- and cell-based assays. CsA
      inhibited BCRP or BCRP R482T mutant-associated ATPase with an IC(50) of 26.1 and
      7.3 microM (31,388 and 8779 ng/ml), respectively, indicating that CsA is a
      modulator for BCRP and its R482T mutant. The apparent permeability (P(app)) of
      CsA was not affected by the BCRP-specific inhibitor Ko143 in both apical-to
      basolateral (A-to-B) and basolateral-to-apical (B-to-A) directions in hBCRP- or
      mBcrp-transfected MDCKII cells, whereas CsA at 50 microM significantly increased
      the A-to-B transport and decreased B-to-A transport of BCRP substrates,
      [(3)H]estrone-3-sulfate ([(3)H]E3S) and [(3)H]methotrexate ([(3)H]MTX), in hBCRP-
      and mBcrp1-trasfected MDCKII cells. Similar to cellular transport studies, CsA
      did not exhibit ATP-dependent uptake in BCRP-expressed membrane vesicles but
      inhibited the ATP-mediated E3S and MTX uptake in the same vesicles. The
      inhibitory constant (K(i)) of CsA toward BCRP was 6.7 microM (8507 ng/ml) and 7.8
      microM (9380 ng/ml) when using E3S or MTX, respectively, as a BCRP substrate. The
      inhibitory potency of CsA on BCRP wild type or its R482T mutant was lower than
      that on P-glycoprotein. The present studies demonstrate that CsA is an inhibitor
      but not a substrate for BCRP, and has low potential to cause drug-drug
      interactions with BCRP substrate drugs due to its weak inhibitory effect on BCRP
      and BCRP R482T mutant at its normal therapeutic blood concentrations (200-400
      ng/ml) (Blood 91:362-363, 1998).

PMID- 17220245
TI  - Role of P-glycoprotein in the intestinal absorption of glabridin, an active
      flavonoid from the root of Glycyrrhiza glabra.
AB  - Glabridin is a major constituent of the root of Glycyrrhiza glabra, which is
      commonly used in the treatment of cardiovascular and central nervous system
      diseases. This study aimed to investigate the role of P-glycoprotein (PgP/MDR1)
      in the intestinal absorption of glabridin. The systemic bioavailability of
      glabridin was approximately 7.5% in rats, but increased when combined with
      verapamil. In single-pass perfused rat ileum with mesenteric vein cannulation,
      the permeability coefficient of glabridin based on drug disappearance in luminal
      perfusates (P(lumen)) was approximately 7-fold higher than that based on drug
      appearance in the blood (P(blood)). Glabridin was mainly metabolized by
      glucuronidation, and the metabolic capacity of intestine microsomes was 1/15 to
      1/20 of that in liver microsomes. Polarized transport of glabridin was found in
      Caco-2 and MDCKII monolayers. Addition of verapamil in both apical (AP) and
      basolateral (BL) sides abolished the polarized transport of glabridin across Caco
      2 cells. Incubation of verapamil significantly altered the intracellular
      accumulation and efflux of glabridin in Caco-2 cells. The transport of glabridin
      in the BL-AP direction was significantly higher in MDCKII cells overexpressing
      PgP/MDR1 than in the control cells. Glabridin inhibited PgP-mediated transport of
      digoxin with an IC(50) value of 2.56 microM, but stimulated PgP/MDR1 ATPase
      activity with a K(m) of 25.1 microM. The plasma AUC(0-24h) of glabridin in mdr1a(
      /-) mice was 3.8-fold higher than that in wild-type mice. These findings indicate
      that glabridin is a substrate for PgP and that both PgP/MDR1-mediated efflux and
      first-pass metabolism contribute to the low oral bioavailability of glabridin.

PMID- 17220246
TI  - Recombinant polycistronic structure of hydantoinase process genes in Escherichia
      coli for the production of optically pure D-amino acids.
AB  - Two recombinant reaction systems for the production of optically pure D-amino
      acids from different D,L-5-monosubstituted hydantoins were constructed. Each
      system contained three enzymes, two of which were D-hydantoinase and D
      carbamoylase from Agrobacterium tumefaciens BQL9. The third enzyme was hydantoin
      racemase 1 for the first system and hydantoin racemase 2 for the second system,
      both from A. tumefaciens C58. Each system was formed by using a recombinant
      Escherichia coli strain with one plasmid harboring three genes coexpressed with
      one promoter in a polycistronic structure. The D-carbamoylase gene was cloned
      closest to the promoter in order to obtain the highest level of synthesis of the
      enzyme, thus avoiding intermediate accumulation, which decreases the reaction
      rate. Both systems were able to produce 100% conversion and 100% optically pure D
      methionine, D-leucine, D-norleucine, D-norvaline, D-aminobutyric acid, D-valine,
      D-phenylalanine, D-tyrosine, and D-tryptophan from the corresponding hydantoin
      racemic mixture. For the production of almost all D-amino acids studied in this
      work, system 1 hydrolyzed the 5-monosubstituted hydantoins faster than system 2.

PMID- 17220247
TI  - Significance of fomites in the spread of respiratory and enteric viral disease.

PMID- 17220248
TI  - Effects of abiotic factors on the phylogenetic diversity of bacterial communities
      in acidic thermal springs.
AB  - Acidic thermal springs offer ideal environments for studying processes underlying
      extremophile microbial diversity. We used a carefully designed comparative
      analysis of acidic thermal springs in Yellowstone National Park to determine how
      abiotic factors (chemistry and temperature) shape acidophile microbial
      communities. Small-subunit rRNA gene sequences were PCR amplified, cloned, and
      sequenced, by using evolutionarily conserved bacterium-specific primers, directly
      from environmental DNA extracted from Amphitheater Springs and Roaring Mountain
      sediment samples. Energy-dispersive X-ray spectroscopy, X-ray diffraction, and
      colorimetric assays were used to analyze sediment chemistry, while an optical
      emission spectrometer was used to evaluate water chemistry and electronic probes
      were used to measure the pH, temperature, and E(h) of the spring waters.
      Phylogenetic-statistical analyses found exceptionally strong correlations between
      bacterial community composition and sediment mineral chemistry, followed by
      weaker but significant correlations with temperature gradients. For example,
      sulfur-rich sediment samples contained a high diversity of uncultured organisms
      related to Hydrogenobaculum spp., while iron-rich sediments were dominated by
      uncultured organisms related to a diverse array of gram-positive iron oxidizers.
      A detailed analysis of redox chemistry indicated that the available energy
      sources and electron acceptors were sufficient to support the metabolic potential
      of Hydrogenobaculum spp. and iron oxidizers, respectively. Principal-component
      analysis found that two factors explained 95% of the genetic diversity, with most
      of the variance attributable to mineral chemistry and a smaller fraction
      attributable to temperature.

PMID- 17220249
TI  - Redirection of metabolism for biological hydrogen production.
AB  - A major route for hydrogen production by purple photosynthetic bacteria is
      biological nitrogen fixation. Nitrogenases reduce atmospheric nitrogen to ammonia
      with the concomitant obligate production of molecular hydrogen. However, hydrogen
      production in the context of nitrogen fixation is a rather inefficient process
      because about 75% of the reductant consumed by the nitrogenase is used to
      generate ammonia. In this study we describe a selection strategy to isolate
      strains of purple photosynthetic bacteria in which hydrogen production is
      necessary for growth and independent of nitrogen fixation. We obtained four
      mutant strains of the photosynthetic bacterium Rhodopseudomonas palustris that
      produce hydrogen constitutively, even in the presence of ammonium, a condition
      where wild-type cells do not accumulate detectable amounts of hydrogen. Some of
      these strains produced up to five times more hydrogen than did wild-type cells
      growing under nitrogen-fixing conditions. Transcriptome analyses of the hydrogen
      producing mutant strains revealed that in addition to the nitrogenase genes, 18
      other genes are potentially required to produce hydrogen. The mutations that
      caused constitutive hydrogen production mapped to four different sites in the
      NifA transcriptional regulator in the four different strains. The strategy
      presented here can be applied to the large number of diverse species of
      anoxygenic photosynthetic bacteria that are known to exist in nature to identify
      strains for which there are fitness incentives to produce hydrogen.

PMID- 17220250
TI  - Microbial diversity within early-stage cultured Panulirus ornatus phyllosomas.
AB  - A thorough understanding of the microorganisms and pathogens associated with the
      larval stage of the tropical ornate rock lobster, Panulirus ornatus, is required
      to overcome disease outbreaks that currently block aquaculture attempts. This
      study used microscopy in addition to culture and molecularly based
      microbiological techniques to characterize the bacterial community associated
      with cultured, developmental stage PI to PII P. ornatus phyllosomas. Scanning
      electron microscopy demonstrated colonization of phyllosomas by filamentous, rod
      shaped, and coccus-shaped bacteria. A clone library constructed from dead
      phyllosomas sampled from the larval rearing tank on day 10 was dominated by
      Thiothrix-affiliated sequences (56% of clones). A comparable library from live
      phyllosomas also contained Thiothrix-affiliated sequences, though these only
      represented 19% of clones within the library. Fluorescent in situ hybridization
      (FISH) confirmed identification of the filamentous bacteria as Thiothrix sp.,
      being present on dead phyllosomas. FISH also identified Leucothrix sp. and Vibrio
      sp., as well as a range of other rod- and coccus-shaped bacteria, colonizing both
      live and dead phyllosomas. The development of the microbial community associated
      with phyllosomas was monitored through a standard larval rearing run using
      denaturing gradient gel electrophoresis (DGGE). Vibrio sp.-affiliated bands
      dominated the profiles of live animals through the rearing period and dead
      phyllosomas sampled on selected days. The population of Vibrio sp. associated
      with phyllosomas was monitored with culture-based analysis on selective media and
      demonstrated to increase significantly on day 7, coinciding with the beginning of
      the larval molt. An isolated Vibrio harveyi strain demonstrated an identical 16S
      rRNA sequence with retrieved DGGE and clone library sequences. Colonization of
      phyllosomas with filamentous bacterial species potentially hinders the ability of
      the animals to molt and, combined with the added stress of the molt process,
      likely results in reduced immune function, allowing opportunistic pathogenic
      Vibrio sp. to cause larval mortalities.

PMID- 17220251
TI  - A portable anaerobic microbioreactor reveals optimum growth conditions for the
      methanogen Methanosaeta concilii.
AB  - Conventional studies of the optimum growth conditions for methanogens (methane
      producing, obligate anaerobic archaea) are typically conducted with serum bottles
      or bioreactors. The use of microfluidics to culture methanogens allows direct
      microscopic observations of the time-integrated response of growth. Here, we
      developed a microbioreactor (microBR) with approximately 1-microl microchannels
      to study some optimum growth conditions for the methanogen Methanosaeta concilii.
      The microBR is contained in an anaerobic chamber specifically designed to place
      it directly onto an inverted light microscope stage while maintaining a N2-CO2
      environment. The methanogen was cultured for months inside microchannels of
      different widths. Channel width was manipulated to create various fluid
      velocities, allowing the direct study of the behavior and responses of M.
      concilii to various shear stresses and revealing an optimum shear level of
      approximately 20 to 35 microPa. Gradients in a single microchannel were then used
      to find an optimum pH level of 7.6 and an optimum total NH4-N concentration of
      less than 1,100 mg/liter (<47 mg/liter as free NH3-N) for M. concilii under
      conditions of the previously determined ideal shear stress and pH and at a
      temperature of 35 degrees C.

PMID- 17220252
TI  - Evaluation of genetic markers and molecular typing methods for prediction of
      sources of Campylobacter jejuni and C. coli infections.
AB  - Campylobacter jejuni and C. coli isolates from poultry, cattle, and humans were
      studied using pulsed-field gel electrophoresis (PFGE) and PCR of candidate
      livestock-associated marker genes. Human isolates showed 5.7 and 61% overlap with
      cattle and poultry isolates, respectively, by use of PFGE. No unambiguous
      association was found between marker genes (the Cj1321 and Cj1324 genes) and
      livestock-associated isolates.

PMID- 17220253
TI  - Screening marine fungi for inhibitors of the C4 plant enzyme pyruvate phosphate
      dikinase: unguinol as a potential novel herbicide candidate.
AB  - A total of 2,245 extracts, derived from 449 marine fungi cultivated in five types
      of media, were screened against the C(4) plant enzyme pyruvate phosphate dikinase
      (PPDK), a potential herbicide target. Extracts from several fungal isolates
      selectively inhibited PPDK. Bioassay-guided fractionation of one isolate led to
      the isolation of the known compound unguinol, which inhibited PPDK with a 50%
      inhibitory concentration of 42.3 +/- 0.8 muM. Further kinetic analysis revealed
      that unguinol was a mixed noncompetitive inhibitor of PPDK with respect to the
      substrates pyruvate and ATP and an uncompetitive inhibitor of PPDK with respect
      to phosphate. Unguinol had deleterious effects on a model C(4) plant but no
      effect on a model C(3) plant. These results indicate that unguinol inhibits PPDK
      via a novel mechanism of action which also translates to an herbicidal effect on
      whole plants.

PMID- 17220254
TI  - Characterization of the prokaryotic diversity in cold saline perennial springs of
      the Canadian high Arctic.
AB  - The springs at Gypsum Hill and Colour Peak on Axel Heiberg Island in the Canadian
      Arctic originate from deep salt aquifers and are among the few known examples of
      cold springs in thick permafrost on Earth. The springs discharge cold anoxic
      brines (7.5 to 15.8% salts), with a mean oxidoreduction potential of -325 mV, and
      contain high concentrations of sulfate and sulfide. We surveyed the microbial
      diversity in the sediments of seven springs by denaturing gradient gel
      electrophoresis (DGGE) and analyzing clone libraries of 16S rRNA genes amplified
      with Bacteria and Archaea-specific primers. Dendrogram analysis of the DGGE
      banding patterns divided the springs into two clusters based on their geographic
      origin. Bacterial 16S rRNA clone sequences from the Gypsum Hill library (spring
      GH-4) were classified into seven phyla (Actinobacteria, Bacteroidetes,
      Firmicutes, Gemmatimonadetes, Proteobacteria, Spirochaetes, and Verrucomicrobia);
      Deltaproteobacteria and Gammaproteobacteria sequences represented half of the
      clone library. Sequences related to Proteobacteria (82%), Firmicutes (9%), and
      Bacteroidetes (6%) constituted 97% of the bacterial clone library from Colour
      Peak (spring CP-1). Most GH-4 archaeal clone sequences (79%) were related to the
      Crenarchaeota while half of the CP-1 sequences were related to orders
      Halobacteriales and Methanosarcinales of the Euryarchaeota. Sequences related to
      the sulfur-oxidizing bacterium Thiomicrospira psychrophila dominated both the GH
      4 (19%) and CP-1 (45%) bacterial libraries, and 56 to 76% of the bacterial
      sequences were from potential sulfur-metabolizing bacteria. These results suggest
      that the utilization and cycling of sulfur compounds may play a major role in the
      energy production and maintenance of microbial communities in these unique, cold
      environments.

PMID- 17220255
TI  - Survey of genomic diversity among Enterococcus faecalis strains by microarray
      based comparative genomic hybridization.
AB  - We have compared nine Enterococcus faecalis strains with E. faecalis V583 by
      comparative genomic hybridization using microarrays (CGH). The strains used in
      this study (the "test" strains) originated from various environments. CGH is a
      powerful and promising tool for obtaining novel information on genome diversity
      in bacteria. By CGH, one obtains clues about which genes are present or divergent
      in the strains, compared to a reference strain (here, V583). The information
      obtained by CGH is important from both ecological and systematic points of view.
      CGH of E. faecalis showed considerable diversity in gene content: Compared to
      V583, the percentage of divergent genes in the test strains varied from 15% to
      23%, and 154 genes were divergent in all strains. The main variation was found in
      regions corresponding to exogenously acquired or mobile DNA in V583. Antibiotic
      resistance genes, virulence factors, and integrated plasmid genes dominated among
      the divergent genes. The strains examined showed various contents of genes
      corresponding to the pTEF1, pTEF2, and pTEF3 genes in V583. The extensive
      transport and metabolic capabilities of V583 appeared similar in the test
      strains; CGH indicated that the ability to transport and metabolize various
      carbohydrates was similar in the test strains (verified by API 50 CH assays). The
      contents of genes related to stress tolerance appeared similar in V583 and the
      nine test strains, supporting the view of E. faecalis as an organism able to
      resist harsh conditions.

PMID- 17220256
TI  - Impact of the direct application of therapeutic agents to the terminal recta of
      experimentally colonized calves on Escherichia coli O157:H7 shedding.
AB  - Enterohemorrhagic Escherichia coli O157:H7 is an important intestinal pathogen of
      humans with a main reservoir of domesticated ruminants, particularly cattle. It
      is anticipated that the risk of human infection can be reduced by controlling the
      organism within its reservoir hosts. Several options for the control of E. coli
      O157:H7 in cattle have been proposed, but none have been demonstrated to be
      successful in the field. Here we describe a novel experimental method, based on
      the terminal-rectum-restricted colonization described previously, to eliminate
      fecal carriage of E. coli O157:H7. In experimentally challenged calves, direct
      application to the rectal mucosa of either of two therapeutic agents, polymyxin B
      or chlorhexidine, greatly reduced bacterial shedding levels in the immediate
      posttreatment period. The most efficacious therapeutic agent, chlorhexidine, was
      compared in orally and rectally challenged calves. The treatment eliminated high
      level shedding and reduced low-level shedding by killing bacteria at the terminal
      rectum. A rapid-detection system based on the ability to identify E. coli O157:H7
      from swabs of the rectal mucosa was also assessed. This test was sufficiently
      sensitive to identify high-level bacterial carriage. Thus, a combination of the
      detection method and treatment regimens could be used in the field to eliminate
      high-level fecal excretion of E. coli O157:H7, so greatly reducing its prevalence
      within this host and the risk of human infection.

PMID- 17220257
TI  - Effect of superoxide dismutase gene inactivation on virulence of Pseudomonas
      aeruginosa PAO1 toward the silkworm, Bombyx mori.
AB  - To investigate the role of superoxide dismutase (SOD) in virulence against the
      silkworm, Bombyx mori, mutants of Pseudomonas aeruginosa PAO1 lacking manganese
      SOD (PAO1sodM), iron-SOD (PAO1sodB), or both (PAO1sodMB) were generated. The
      mutants were injected into the hemocoel of B. mori. The virulence decreased in
      the order PAO1=PAO1sodM>PAO1sodB>PAO1sodMB. In particular, PAO1sodMB was
      avirulent at a dose of 10(5) cells or less. The sod double mutant PAO1sodMB was
      then complemented with either pSodM or pSodB in trans. In both the complemented
      strains, the virulence was partially restored. Of the two plasmids, pSodB
      contributed more to the virulence of P. aeruginosa against B. mori. The results
      of growth in B. mori hemolymph broth and microscopic analysis suggested that a
      longer lag phase and superoxide sensitivity correlated with decreased virulence
      in sod mutants. In conclusion, the SODs are required for full virulence of P.
      aeruginosa against B. mori and Fe-SOD is more important than Mn-SOD in the
      infection process.

PMID- 17220258
TI  - In planta horizontal transfer of a major pathogenicity effector gene.
AB  - Xanthomonas citri pv. citri is a clonal group of strains that causes citrus
      canker disease and appears to have originated in Asia. A phylogenetically
      distinct clonal group that causes identical disease symptoms on susceptible
      citrus, X. citri pv. aurantifolii, arose more recently in South America. Genomes
      of X. citri pv. aurantifolii strains carry two DNA fragments that hybridize to
      pthA, an X. citri pv. citri gene which encodes a major type III pathogenicity
      effector protein that is absolutely required to cause citrus canker. Marker
      interruption mutagenesis and complementation revealed that X. citri pv.
      aurantifolii strain B69 carried one functional pthA homolog, designated pthB,
      that was required to cause cankers on citrus. Gene pthB was found among 38 open
      reading frames on a 37,106-bp plasmid, designated pXcB, which was sequenced and
      annotated. No additional pathogenicity effectors were found on pXcB, but 11 out
      of 38 open reading frames appeared to encode a type IV transfer system. pXcB
      transferred horizontally in planta, without added selection, from B69 to a
      nonpathogenic X. citri pv. citri (pthA::Tn5) mutant strain, fully restoring
      canker. In planta transfer efficiencies were very high (>0.1%/recipient) and
      equivalent to those observed for agar medium with antibiotic selection,
      indicating that pthB conferred a strong selective advantage to the recipient
      strain. A single pathogenicity effector that can confer a distinct selective
      advantage in planta may both facilitate plasmid survival following horizontal
      gene transfer and account for the origination of phylogenetically distinct groups
      of strains causing identical disease symptoms.

PMID- 17220259
TI  - Evolutionary relationships of "Candidatus Riesia spp.," endosymbiotic
      enterobacteriaceae living within hematophagous primate lice.
AB  - The primary endosymbiotic bacteria from three species of parasitic primate lice
      were characterized molecularly. We have confirmed the characterization of the
      primary endosymbiont (P-endosymbiont) of the human head/body louse Pediculus
      humanus and provide new characterizations of the P-endosymbionts from Pediculus
      schaeffi from chimpanzees and Pthirus pubis, the pubic louse of humans. The
      endosymbionts show an average percent sequence divergence of 11 to 15% from the
      most closely related known bacterium "Candidatus Arsenophonus insecticola." We
      propose that two additional species be added to the genus "Candidatus Riesia."
      The new species proposed within "Candidatus Riesia" have sequence divergences of
      3.4% and 10 to 12% based on uncorrected pairwise differences. Our Bayesian
      analysis shows that the branching pattern for the primary endosymbionts was the
      same as that for their louse hosts, suggesting a long coevolutionary history
      between primate lice and their primary endosymbionts. We used a calibration of
      5.6 million years to date the divergence between endosymbionts from human and
      chimpanzee lice and estimated an evolutionary rate of nucleotide substitution of
      0.67% per million years, which is 15 to 30 times faster than previous estimates
      calculated for Buchnera, the primary endosymbiont in aphids. Given the evidence
      for cospeciation with primate lice and the evidence for fast evolutionary rates,
      this lineage of endosymbiotic bacteria can be evaluated as a fast-evolving marker
      of both louse and primate evolutionary histories.

PMID- 17220260
TI  - Carbon conversion efficiency and limits of productive bacterial degradation of
      methyl tert-butyl ether and related compounds.
AB  - The utilization of the fuel oxygenate methyl tert-butyl ether (MTBE) and related
      compounds by microorganisms was investigated in a mainly theoretical study based
      on the Y(ATP) concept. Experiments were conducted to derive realistic maintenance
      coefficients and K(s) values needed to calculate substrate fluxes available for
      biomass production. Aerobic substrate conversion and biomass synthesis were
      calculated for different putative pathways. The results suggest that MTBE is an
      effective heterotrophic substrate that can sustain growth yields of up to 0.87 g
      g(-1), which contradicts previous calculation results (N. Fortin et al., Environ.
      Microbiol. 3:407-416, 2001). Sufficient energy equivalents were generated in
      several of the potential assimilatory routes to incorporate carbon into biomass
      without the necessity to dissimilate additional substrate, efficient energy
      transduction provided. However, when a growth-related kinetic model was included,
      the limits of productive degradation became obvious. Depending on the maintenance
      coefficient m(s) and its associated biomass decay term b, growth-associated
      carbon conversion became strongly dependent on substrate fluxes. Due to slow
      degradation kinetics, the calculations predicted relatively high threshold
      concentrations, S(min), below which growth would not further be supported. S(min)
      strongly depended on the maximum growth rate mu(ma)(x), and b and was directly
      correlated with the half maximum rate-associated substrate concentration K(s),
      meaning that any effect impacting this parameter would also change S(min). The
      primary metabolic step, catalyzing the cleavage of the ether bond in MTBE, is
      likely to control the substrate flux in various strains. In addition, deficits in
      oxygen as an external factor and in reduction equivalents as a cellular variable
      in this reaction should further increase K(s) and S(min) for MTBE.

PMID- 17220261
TI  - Identification of a sterol Delta7 reductase gene involved in desmosterol
      biosynthesis in Mortierella alpina 1S-4.
AB  - Molecular cloning of the gene encoding sterol Delta7 reductase from the
      filamentous fungus Mortierella alpina 1S-4, which accumulates cholesta-5,24
      dienol (desmosterol) as the main sterol, revealed that the open reading frame of
      this gene, designated MoDelta7SR, consists of 1,404 bp and codes for 468 amino
      acids with a molecular weight of 53,965. The predicted amino acid sequence of
      MoDelta7SR showed highest homology of 51% with that of sterol Delta7 reductase
      (EC 1.3.1.21) from Xenopus laevis (African clawed frog). Heterologous expression
      of the MoDelta7SR gene in yeast Saccharomyces cerevisiae revealed that MoDelta7SR
      converts ergosta-5,7-dienol to ergosta-5-enol (campesterol) by the activity of
      Delta7 reductase. In addition, with gene silencing of MoDelta7SR gene by RNA
      interference, the transformant accumulated cholesta-5,7,24-trienol up to 10% of
      the total sterols with a decrease in desmosterol. Cholesta-5,7,24-trienol is not
      detected in the control strain. This indicates that MoDelta7SR is involved in
      desmosterol biosynthesis in M. alpina 1S-4. This study is the first report on
      characterization of sterol Delta7 reductase from a microorganism.

PMID- 17220262
TI  - Detection of Vibrio cholerae by real-time nucleic acid sequence-based
      amplification.
AB  - A multitarget molecular beacon-based real-time nucleic acid sequence-based
      amplification (NASBA) assay for the specific detection of Vibrio cholerae has
      been developed. The genes encoding the cholera toxin (ctxA), the toxin
      coregulated pilus (tcpA; colonization factor), the ctxA toxin regulator (toxR),
      hemolysin (hlyA), and the 60-kDa chaperonin product (groEL) were selected as
      target sequences for detection. The beacons for the five different genetic
      targets were evaluated by serial dilution of RNA from V. cholerae cells. RNase
      treatment of the nucleic acids eliminated all NASBA, whereas DNase treatment had
      no effect, showing that RNA and not DNA was amplified. The specificity of the
      assay was investigated by testing several isolates of V. cholerae, other Vibrio
      species, and Bacillus cereus, Salmonella enterica, and Escherichia coli strains.
      The toxR, groEL, and hlyA beacons identified all V. cholerae isolates, whereas
      the ctxA and tcpA beacons identified the O1 toxigenic clinical isolates. The
      NASBA assay detected V. cholerae at 50 CFU/ml by using the general marker groEL
      and tcpA that specifically indicates toxigenic strains. A correlation between
      cell viability and NASBA was demonstrated for the ctxA, toxR, and hlyA targets.
      RNA isolated from different environmental water samples spiked with V. cholerae
      was specifically detected by NASBA. These results indicate that NASBA can be used
      in the rapid detection of V. cholerae from various environmental water samples.
      This method has a strong potential for detecting toxigenic strains by using the
      tcpA and ctxA markers. The entire assay including RNA extraction and NASBA was
      completed within 3 h.

PMID- 17220263
TI  - Rectoanal junction colonization of feedlot cattle by Escherichia coli O157:H7 and
      its association with supershedders and excretion dynamics.
AB  - Feedlot cattle were observed for fecal excretion of and rectoanal junction (RAJ)
      colonization with Escherichia coli O157:H7 to identify potential "supershedders."
      RAJ colonization and fecal excretion prevalences were correlated, and E. coli
      O157:H7 prevalences and counts were significantly greater for RAJ samples. Based
      on a comparison of RAJ and fecal ratios of E. coli O157:H7/E. coli counts, the
      RAJ appears to be preferentially colonized by the O157:H7 serotype. Five
      supershedders were identified based on persistent colonization with high
      concentrations of E. coli O157:H7. Cattle copenned with supershedders had
      significantly greater mean pen E. coli O157:H7 RAJ and fecal prevalences than
      noncopenned cattle. Cumulative fecal E. coli O157:H7 excretion was also
      significantly higher for pens housing a supershedder. E. coli O157:H7/E. coli
      count ratios were higher for supershedders than for other cattle, indicating
      greater proportional colonization. Pulsed-field gel electrophoresis analysis
      demonstrated that isolates from supershedders and copenned cattle were highly
      related. Cattle that remained negative for E. coli O157:H7 throughout sampling
      were five times more likely to have been in a pen that did not house a
      supershedder. The data from this study support an association between levels of
      fecal excretion of E. coli O157:H7 and RAJ colonization in pens of feedlot cattle
      and suggest that the presence of supershedders influences group-level excretion
      parameters. An improved understanding of individual and population transmission
      dynamics of E. coli O157:H7 can be used to develop preslaughter- and slaughter
      level interventions that reduce contamination of the food chain.

PMID- 17220264
TI  - Autotransporter-encoding sequences are phylogenetically distributed among
      Escherichia coli clinical isolates and reference strains.
AB  - Autotransporters are secreted bacterial proteins exhibiting diverse virulence
      functions. Various autotransporters have been identified among Escherichia coli
      associated with intestinal or extraintestinal infections; however, the specific
      distribution of autotransporter sequences among a diversity of E. coli strains
      has not been investigated. We have validated the use of a multiplex PCR assay to
      screen for the presence of autotransporter sequences. Herein, we determined the
      presence of 13 autotransporter sequences and five allelic variants of antigen 43
      (Ag43) among 491 E. coli isolates from human urinary tract infections,
      diarrheagenic E. coli, and avian pathogenic E. coli (APEC) and E. coli reference
      strains belonging to the ECOR collection. Clinical isolates were also classified
      into established phylogenetic groups. The results indicated that Ag43 alleles
      were significantly associated with clinical isolates (93%) compared to commensal
      isolates (56%) and that agn43K12 was the most common and widely distributed
      allele. agn43 allelic variants were also phylogenetically distributed. Sequences
      encoding espC, espP, and sepA and agn43 alleles EDL933 and RS218 were
      significantly associated with diarrheagenic E. coli strains compared to other
      groups. tsh was highly associated with APEC strains, whereas sat was absent from
      APEC. vat, sat, and pic were associated with urinary tract isolates and were
      identified predominantly in isolates belonging to either group B2 or D of the
      phylogenetic groups based on the ECOR strain collection. Overall, the results
      indicate that specific autotransporter sequences are associated with the source
      and/or phylogenetic background of strains and suggest that, in some cases,
      autotransporter gene profiles may be useful for comparative analysis of E. coli
      strains from clinical, food, and environmental sources.

PMID- 17220265
TI  - Adaptation of a luciferase gene reporter and lac expression system to Borrelia
      burgdorferi.
AB  - The development of new genetic systems for studying the complex regulatory events
      that occur within Borrelia burgdorferi is an important goal of contemporary Lyme
      disease research. Although recent advancements have been made in the genetic
      manipulation of B. burgdorferi, there still remains a paucity of basic molecular
      systems for assessing differential gene expression in this pathogen. Herein, we
      describe the adaptation of two powerful genetic tools for use in B. burgdorferi.
      The first is a Photinus pyralis firefly luciferase gene reporter that was codon
      optimized to enhance translation in B. burgdorferi. Using this modified reporter,
      we demonstrated an increase in luciferase expression when B. burgdorferi
      transformed with a shuttle vector encoding the outer surface protein C (OspC)
      promoter fused to the luciferase reporter was cultivated in the presence of fresh
      rabbit blood. The second is a lac operator/repressor system that was optimized to
      achieve the tightest degree of regulation. Using the aforementioned luciferase
      reporter, we assessed the kinetics and maximal level of isopropyl-beta-D
      thiogalactopyranoside (IPTG)-dependent gene expression. This lac-inducible
      expression system also was used to express the gene carried on lp25 required for
      borrelial persistence in ticks (bptA). These advancements should be generally
      applicable for assessing further the regulation of other genes potentially
      involved in virulence expression by B. burgdorferi.

PMID- 17220266
TI  - The presence of the internalin gene in natural atypically hemolytic Listeria
      innocua strains suggests descent from L. monocytogenes.
AB  - The atypical hemolytic Listeria innocua strains PRL/NW 15B95 and J1-023 were
      previously shown to contain gene clusters analogous to the pathogenicity island
      (LIPI-1) present in the related foodborne gram-positive facultative intracellular
      pathogen Listeria monocytogenes, which causes listeriosis. LIPI-1 includes the
      hemolysin gene, thus explaining the hemolytic activity of the atypical L. innocua
      strains. No other L. monocytogenes-specific virulence genes were found to be
      present. In order to investigate whether any other specific L. monocytogenes
      genes could be identified, a global approach using a Listeria biodiversity DNA
      array was applied. According to the hybridization results, the isolates were
      defined as L. innocua strains containing LIPI-1. Surprisingly, evidence for the
      presence of the L. monocytogenes-specific inlA gene, previously thought to be
      absent, was obtained. The inlA gene codes for the InlA protein which enables
      bacterial entry into some nonprofessional phagocytic cells. PCR and sequence
      analysis of this region revealed that the flanking genes of the inlA gene at the
      upstream, 5'-end region were similar to genes found in L. monocytogenes serotype
      4b isolates, whereas the organization of the downstream, 3'-end region was
      similar to that typical of L. innocua. Sequencing of the inlA region identified a
      small stretch reminiscent of the inlB gene of L. monocytogenes. The presence of
      two clusters of L. monocytogenes-specific genes makes it unlikely that PRL/NW
      15B95 and J1-023 are L. innocua strains altered by horizontal transfer. It is
      more likely that they are distinct relics of the evolution of L. innocua from an
      ancestral L. monocytogenes, as postulated by others.

PMID- 17220267
TI  - Histidine decarboxylases and their role in accumulation of histamine in tuna and
      dried saury.
AB  - Histamine-producing bacteria (HPB) such as Photobacterium phosphoreum and
      Raoultella planticola possess histidine decarboxylase (HDC), which converts
      histidine into histamine. Histamine fish poisoning (HFP) is attributable to the
      ingestion of fish containing high levels of histamine produced by HPB. Because
      freezing greatly decreases the histamine-producing ability of HPB, especially of
      P. phosphoreum, it has been speculated that HFP is caused by HDC itself from HPB
      cells autolyzing during frozen storage, even when HPB survive frozen storage.
      Here we constructed recombinant HDCs of P. phosphoreum, Photobacterium damselae,
      R. planticola, and Morganella morganii and investigated the ability of HDCs to
      produce sufficient histamine to cause HFP. To elucidate the character of these
      HDCs, we examined the specific activity of each recombinant HDC at various
      temperatures, pH levels, and NaCl concentrations. Further, we also investigated
      the stability of each HDC under different conditions (in reaction buffer, tuna,
      and dried saury) at various temperatures. P. damselae HDC readily produced
      sufficient histamine to cause HFP in fish samples. We consider that if HDC is
      implicated as an independent cause of HFP in frozen-thawed fish, the most likely
      causative agent is HDC of P. damselae.

PMID- 17220268
TI  - Quantitative and qualitative beta diversity measures lead to different insights
      into factors that structure microbial communities.
AB  - The assessment of microbial diversity and distribution is a major concern in
      environmental microbiology. There are two general approaches for measuring
      community diversity: quantitative measures, which use the abundance of each
      taxon, and qualitative measures, which use only the presence/absence of data.
      Quantitative measures are ideally suited to revealing community differences that
      are due to changes in relative taxon abundance (e.g., when a particular set of
      taxa flourish because a limiting nutrient source becomes abundant). Qualitative
      measures are most informative when communities differ primarily by what can live
      in them (e.g., at high temperatures), in part because abundance information can
      obscure significant patterns of variation in which taxa are present. We
      illustrate these principles using two 16S rRNA-based surveys of microbial
      populations and two phylogenetic measures of community beta diversity: unweighted
      UniFrac, a qualitative measure, and weighted UniFrac, a new quantitative measure,
      which we have added to the UniFrac website (http://bmf.colorado.edu/unifrac).
      These studies considered the relative influences of mineral chemistry,
      temperature, and geography on microbial community composition in acidic thermal
      springs in Yellowstone National Park and the influences of obesity and kinship on
      microbial community composition in the mouse gut. We show that applying
      qualitative and quantitative measures to the same data set can lead to
      dramatically different conclusions about the main factors that structure
      microbial diversity and can provide insight into the nature of community
      differences. We also demonstrate that both weighted and unweighted UniFrac
      measurements are robust to the methods used to build the underlying phylogeny.

PMID- 17220269
TI  - The crystal structure of the Escherichia coli AmtB-GlnK complex reveals how GlnK
      regulates the ammonia channel.
AB  - Amt proteins are ubiquitous channels for the conduction of ammonia in archaea,
      eubacteria, fungi, and plants. In Escherichia coli, previous studies have
      indicated that binding of the PII signal transduction protein GlnK to the ammonia
      channel AmtB regulates the channel thereby controlling ammonium influx in
      response to the intracellular nitrogen status. Here, we describe the crystal
      structure of the complex between AmtB and GlnK at a resolution of 2.5 A. This
      structure of PII in a complex with one of its targets reveals physiologically
      relevant conformations of both AmtB and GlnK. GlnK interacts with AmtB almost
      exclusively via a long surface loop containing Y51 (T-loop), the tip of which
      inserts deeply into the cytoplasmic pore exit, blocking ammonia conduction. Y51
      of GlnK is also buried in the pore exit, explaining why uridylylation of this
      residue prevents complex formation.

PMID- 17220271
TI  - Fast marching methods for the continuous traveling salesman problem.
AB  - We consider a problem in which we are given a domain, a cost function which
      depends on position at each point in the domain, and a subset of points
      ("cities") in the domain. The goal is to determine the cheapest closed path that
      visits each city in the domain once. This can be thought of as a version of the
      traveling salesman problem, in which an underlying known metric determines the
      cost of moving through each point of the domain, but in which the actual shortest
      path between cities is unknown at the outset. We describe algorithms for both a
      heuristic and an optimal solution to this problem. The complexity of the
      heuristic algorithm is at worst case M.N log N, where M is the number of cities,
      and N the size of the computational mesh used to approximate the solutions to the
      shortest paths problems. The average runtime of the heuristic algorithm is linear
      in the number of cities and O(N log N) in the size N of the mesh.

PMID- 17220270
TI  - Serum proteome profiling detects myelodysplastic syndromes and identifies CXC
      chemokine ligands 4 and 7 as markers for advanced disease.
AB  - Myelodysplastic syndromes (MDS) are among the most frequent hematologic
      malignancies. Patients have a short survival and often progress to acute myeloid
      leukemia. The diagnosis of MDS can be difficult; there is a paucity of molecular
      markers, and the pathophysiology is largely unknown. Therefore, we conducted a
      multicenter study investigating whether serum proteome profiling may serve as a
      noninvasive platform to discover novel molecular markers for MDS. We generated
      serum proteome profiles from 218 individuals by MS and identified a profile that
      distinguishes MDS from non-MDS cytopenias in a learning sample set. This profile
      was validated by testing its ability to predict MDS in a first independent
      validation set and a second, prospectively collected, independent validation set
      run 5 months apart. Accuracy was 80.5% in the first and 79.0% in the second
      validation set. Peptide mass fingerprinting and quadrupole TOF MS identified two
      differential proteins: CXC chemokine ligands 4 (CXCL4) and 7 (CXCL7), both of
      which had significantly decreased serum levels in MDS, as confirmed with
      independent antibody assays. Western blot analyses of platelet lysates for these
      two platelet-derived molecules revealed a lack of CXCL4 and CXCL7 in MDS. Subtype
      analyses revealed that these two proteins have decreased serum levels in advanced
      MDS, suggesting the possibility of a concerted disturbance of transcription or
      translation of these chemokines in advanced MDS.

PMID- 17220272
TI  - Six-rowed barley originated from a mutation in a homeodomain-leucine zipper I
      class homeobox gene.
AB  - Increased seed production has been a common goal during the domestication of
      cereal crops, and early cultivators of barley (Hordeum vulgare ssp. vulgare)
      selected a phenotype with a six-rowed spike that stably produced three times the
      usual grain number. This improved yield established barley as a founder crop for
      the Near Eastern Neolithic civilization. The barley spike has one central and two
      lateral spikelets at each rachis node. The wild-type progenitor (H. vulgare ssp.
      spontaneum) has a two-rowed phenotype, with additional, strictly rudimentary,
      lateral rows; this natural adaptation is advantageous for seed dispersal after
      shattering. Until recently, the origin of the six-rowed phenotype remained
      unknown. In the present study, we isolated vrs1 (six-rowed spike 1), the gene
      responsible for the six-rowed spike in barley, by means of positional cloning.
      The wild-type Vrs1 allele (for two-rowed barley) encodes a transcription factor
      that includes a homeodomain with a closely linked leucine zipper motif.
      Expression of Vrs1 was strictly localized in the lateral-spikelet primordia of
      immature spikes, suggesting that the VRS1 protein suppresses development of the
      lateral rows. Loss of function of Vrs1 resulted in complete conversion of the
      rudimentary lateral spikelets in two-rowed barley into fully developed fertile
      spikelets in the six-rowed phenotype. Phylogenetic analysis demonstrated that the
      six-rowed phenotype originated repeatedly, at different times and in different
      regions, through independent mutations of Vrs1.

PMID- 17220273
TI  - Rapid evolution of flowering time by an annual plant in response to a climate
      fluctuation.
AB  - Ongoing climate change has affected the ecological dynamics of many species and
      is expected to impose natural selection on ecologically important traits.
      Droughts and other anticipated changes in precipitation may be particularly
      potent selective factors, especially in arid regions. Here we demonstrate the
      evolutionary response of an annual plant, Brassica rapa, to a recent climate
      fluctuation resulting in a multiyear drought. Ancestral (predrought) genotypes
      were recovered from stored seed and raised under a set of common environments
      with descendant (postdrought) genotypes and with ancestorxdescendant hybrids. As
      predicted, the abbreviated growing seasons caused by drought led to the evolution
      of earlier onset of flowering. Descendants bloomed earlier than ancestors,
      advancing first flowering by 1.9 days in one study population and 8.6 days in
      another. The intermediate flowering time of ancestorxdescendant hybrids supports
      an additive genetic basis for divergence. Experiments confirmed that summer
      drought selected for early flowering, that flowering time was heritable, and that
      selection intensities in the field were more than sufficient to account for the
      observed evolutionary change. Natural selection for drought escape thus appears
      to have caused adaptive evolution in just a few generations. A systematic effort
      to collect and store propagules from suitable species would provide biologists
      with materials to detect and elucidate the genetic basis of further evolutionary
      shifts driven by climate change.

PMID- 17220274
TI  - Deception point: peptidoglycan modification as a means of immune evasion.

PMID- 17220275
TI  - The hypoxia-inducible factor 2alpha N-terminal and C-terminal transactivation
      domains cooperate to promote renal tumorigenesis in vivo.
AB  - Hypoxia-inducible factor (HIF) is a heterodimeric transcription factor,
      consisting of an alpha subunit and a beta subunit, that controls cellular
      responses to hypoxia. HIFalpha contains two transcriptional activation domains
      called the N-terminal transactivation domain (NTAD) and the C-terminal
      transactivation domain (CTAD). HIFalpha is destabilized by prolyl hydroxylation
      catalyzed by EglN family members. In addition, CTAD function is inhibited by
      asparagine hydroxylation catalyzed by FIH1. Both hydroxylation reactions are
      linked to oxygen availability. The von Hippel-Lindau tumor suppressor protein
      (pVHL) is frequently mutated in kidney cancer and is part of the ubiquitin ligase
      complex that targets prolyl hydroxylated HIFalpha for destruction. Recent studies
      suggest that HIF2alpha plays an especially important role in promoting tumor
      formation by pVHL-defective renal carcinoma cells among the three HIFalpha
      paralogs. Here we dissected the relative contribution of the two HIF2alpha
      transactivation domains to hypoxic gene activation and renal carcinogenesis and
      investigated the regulation of the HIF2alpha CTAD by FIH1. We found that the
      HIF2alpha NTAD is capable of activating both artificial and naturally occurring
      HIF-responsive promoters in the absence of the CTAD. Moreover, we found that the
      HIF2alpha CTAD, in contrast to the HIF1alpha CTAD, is relatively resistant to the
      inhibitory effects of FIH1 under normoxic conditions and that, perhaps as a
      result, both the NTAD and CTAD cooperate to promote renal carcinogenesis in vivo.

PMID- 17220277
TI  - Physical and functional interactions between homeodomain NKX2.1 and winged
      helix/forkhead FOXA1 in lung epithelial cells.
AB  - NKX2.1 is a homeodomain transcription factor that controls development of the
      brain, lung, and thyroid. In the lung, Nkx2.1 is expressed in a proximo-distal
      gradient and activates specific genes in phenotypically distinct epithelial cells
      located along this axis. The mechanisms by which NKX2.1 controls its target genes
      may involve interactions with other transcription factors. We examined whether
      NKX2.1 interacts with members of the winged-helix/forkhead family of FOXA
      transcription factors to regulate two spatially and cell type-specific genes, SpC
      and Ccsp. The results show that NKX2.1 interacts physically and functionally with
      FOXA1. The nature of the interaction is inhibitory and occurs through the NKX2.1
      homeodomain in a DNA-independent manner. On SpC, which lacks a FOXA1 binding
      site, FOXA1 attenuates NKX2.1-dependent transcription. Inhibition of FOXA1 by
      small interfering RNA increased SpC mRNA, demonstrating the in vivo relevance of
      this finding. In contrast, FOXA1 and NKX2.1 additively activate transcription
      from Ccsp, which includes both NKX2.1 and FOXA1 binding sites. In electrophoretic
      mobility shift assays, the GST-FOXA1 fusion protein interferes with the formation
      of NKX2.1 transcriptional complexes by potentially masking the latter's
      homeodomain DNA binding function. These findings suggest a novel mode of
      selective gene regulation by proximo-distal gradient distribution of and
      functional interactions between forkhead and homeodomain transcription factors.

PMID- 17220276
TI  - Genome maintenance defects in cultured cells and mice following partial
      inactivation of the essential cell cycle checkpoint gene Hus1.
AB  - Cell cycle checkpoints are evolutionarily conserved signaling pathways that
      uphold genomic integrity. Complete inactivation of the mouse checkpoint gene Hus1
      results in chromosomal instability, genotoxin hypersensitivity, and embryonic
      lethality. To determine the functional consequences of partial Hus1 impairment,
      we generated an allelic series in which Hus1 expression was incrementally reduced
      by combining a hypomorphic Hus1 allele, Hus1(neo), with either wild-type or null
      (Hus1(Delta1)) alleles. Primary Hus1(neo/Delta1) embryonic fibroblasts exhibited
      spontaneous chromosomal abnormalities and underwent premature senescence, while
      higher Hus1 expression in Hus1(neo/neo) cells allowed for normal proliferation.
      Antioxidant treatment almost fully suppressed premature senescence in
      Hus1(neo/Delta1) cultures, suggesting a critical role for Hus1 in oxidative
      stress responses. Treatment of Hus1(neo/neo) and Hus1(neo/Delta1) cells with the
      DNA adducting agent benzo(a)pyrene dihydrodriol epoxide resulted in a loss of
      cell viability that was associated with S-phase DNA damage checkpoint failure.
      Likewise, the DNA polymerase inhibitor aphidicolin triggered increased cell
      death, chromosomal aberrations, and H2AX phosphorylation, a marker for double
      stranded DNA breaks, in Hus1(neo/neo) and Hus1(neo/Delta1) cultures compared to
      controls. Despite these pronounced genome maintenance defects in cultured
      Hus1(neo/Delta1) and Hus1(neo/neo) cells, mice of the same genotypes were born at
      expected frequencies and appeared grossly normal. A significant increase in
      micronucleus formation was observed in peripheral blood cells from
      Hus1(neo/Delta1) mice, but reduced Hus1 expression did not cause an elevated
      predisposition to spontaneous tumor development or accelerate tumorigenesis in
      p53-deficient mice. These results identify differential effects of altered Hus1
      gene dosage on genome maintenance during in vitro culture, genotoxic stress
      responses, embryonic development, and adult homeostasis.

PMID- 17220278
TI  - Glucocorticoid and growth factor synergism requirement for Notch4 chromatin
      domain activation.
AB  - The Notch signaling pathway modulates cell fate in diverse contexts, including
      vascular development. Notch4 is selectively expressed in vascular endothelium and
      regulates vascular remodeling. The signal-dependent transcription factor
      activator protein 1 (AP-1) activates Notch4 transcription in endothelial cells,
      but other factors/signals that regulate Notch4 are largely unknown. We
      demonstrate that, unlike the established transrepression mechanism in which the
      glucocorticoid receptor (GR) antagonizes AP-1, AP-1 and GR synergistically
      activated Notch4 transcription in endothelial cells. Fibroblast growth factor 2
      (FGF-2) and cortisol induced AP-1 and GR occupancy, respectively, at a Notch4
      promoter composite response element consisting of an imperfect half
      glucocorticoid response element and an AP-1 motif, which mediated signal
      dependent activation. Analysis of Notch4 promoter complex assembly provided
      evidence that GR and AP-1 independently occupy the composite response element,
      but AP-1 stabilizes GR occupancy. In multipotent 10T1/2 cells, FGF-2 and cortisol
      induced a histone modification pattern at the Notch4 locus mimicking that present
      in endothelial cells and reprogrammed Notch4 from a repressed to an active state.
      These results establish the molecular basis for a novel AP-1/GR-Notch4 axis in
      vascular endothelium.

PMID- 17220279
TI  - hDREF regulates cell proliferation and expression of ribosomal protein genes.
AB  - Although ribosomal proteins (RPs) are essential cellular constituents in all
      living organisms, mechanisms underlying regulation of their gene expression in
      mammals remain unclear. We have established that 22 out of 79 human RP genes
      contain sequences similar to the human DREF (DNA replication-related element
      binding factor; hDREF) binding sequence (hDRE) within 200-bp regions upstream of
      their transcriptional start sites. Electrophoretic gel mobility shift assays and
      chromatin immunoprecipitation analysis indicated that hDREF binds to hDRE-like
      sequences in the RP genes both in vitro and in vivo. In addition, transient
      luciferase assays revealed that hDRE-like sequences act as positive elements for
      RP gene transcription and cotransfection of an hDREF-expressing plasmid was found
      to stimulate RP gene promoter activity. Like that of hDREF, expression of RP
      genes is increased during the late G(1) to S phases, and depletion of hDREF using
      short hairpin RNA-mediated knockdown decreased RP gene expression and cell
      proliferation in normal human fibroblasts. Knockdown of the RPS6 gene also
      resulted in impairment of cell proliferation. These data suggest that hDREF is an
      important transcription factor for cell proliferation which plays roles in cell
      cycle-dependent regulation of a number of RP genes.

PMID- 17220280
TI  - Impaired adipogenesis caused by a mutated thyroid hormone alpha1 receptor.
AB  - Thyroid hormone (T3) is critical for growth, differentiation, and maintenance of
      metabolic homeostasis. Mice with a knock-in mutation in the thyroid hormone
      receptor alpha gene (TRalpha1PV) were created previously to explore the roles of
      mutated TRalpha1 in vivo. TRalpha1PV is a dominant negative mutant with a
      frameshift mutation in the carboxyl-terminal 14 amino acids that results in the
      loss of T3 binding and transcription capacity. Homozygous knock-in
      TRalpha1(PV/PV) mice are embryonic lethal, and heterozygous TRalpha1(PV/+) mice
      display the striking phenotype of dwarfism. These mutant mice provide a valuable
      tool for identifying the defects that contribute to dwarfism. Here we show that
      white adipose tissue (WAT) mass was markedly reduced in TRalpha1(PV/+) mice. The
      expression of peroxisome proliferator-activated receptor gamma (PPARgamma), the
      key regulator of adipogenesis, was repressed at both mRNA and protein levels in
      WAT of TRalpha1(PV/+) mice. Moreover, TRalpha1PV acted to inhibit the
      transcription activity of PPARgamma by competition with PPARgamma for binding to
      PPARgamma response elements and for heterodimerization with the retinoid X
      receptors. The expression of TRalpha1PV blocked the T3-dependent adipogenesis of
      3T3-L1 cells and repressed the expression of PPARgamma. Thus, mutations of
      TRalpha1 severely affect adipogenesis via cross talk with PPARgamma signaling.
      The present study suggests that defects in adipogenesis could contribute to the
      phenotypic manifestation of reduced body weight in TRalpha1(PV/+) mice.

PMID- 17220281
TI  - Positive and negative regulation of Tetrahymena telomerase holoenzyme.
AB  - Telomerase replenishes the telomeric repeats that cap eukaryotic chromosome ends.
      To perform DNA synthesis, the active site of telomerase reverse transcriptase
      (TERT) copies a template within the integral telomerase RNA (TER). In vivo, TERT
      and TER and additional subunits form a telomerase holoenzyme capable of telomere
      elongation. We previously purified epitope-tagged Tetrahymena thermophila TERT
      and characterized two of the associated proteins. Here we characterize the
      remaining two proteins that were enriched by TERT purification. The primary
      sequence of the p75 polypeptide lacks evident homology with other proteins,
      whereas the p20 polypeptide is the Tetrahymena ortholog of a conserved
      multifunctional protein, Skp1. Genetic depletion of p75 induced telomere
      shortening without affecting the accumulation of TER or TERT, suggesting that p75
      promotes telomerase function at the telomere. Affinity purification of p75
      coenriched telomerase activity and each other known telomerase holoenzyme
      protein. On the other hand, genetic depletion of Skp1p induced telomere
      elongation, suggesting that this protein plays a negative regulatory role in the
      maintenance of telomere length homeostasis. Affinity purification of Skp1p did
      not detectably enrich active telomerase but did copurify ubiquitin ligase
      machinery. These studies reveal additional complexity in the positive and
      negative regulation of Tetrahymena telomerase function.

PMID- 17220283
TI  - It is too early to know if intelligence determines cancer incidence and survival.

PMID- 17220284
TI  - IQ in early adulthood and later cancer risk: cohort study of one million Swedish
      men.
AB  - BACKGROUND: While several studies have reported an inverse relation between IQ
      and total mortality rates, little is known about the association, if any, between
      IQ and disease-specific outcomes, particularly cancer. METHODS: A cohort of
      959,540 Swedish men who underwent IQ testing at military conscription at around
      19 years of age, and who were followed for incident cancer. Hazards ratios for
      the relation between IQ and 20 cancer outcomes were computed using Cox
      regression. RESULTS: During an average of 19.5 years of follow-up, there were 10
      273 new cancer cases. IQ showed few associations with the cancer end points
      studied. There was a suggestion that IQ was positively associated with lung
      cancer, and inversely related to stomach, oesophageal and liver malignancies,
      although effects were modest. The only robust gradient was found for IQ in
      relation to skin cancer (HRper one standard deviation advantage in IQ; 95%
      confidence interval 1.18; 1.13, 1.24; P value for trend across categories:
      <0.01), which was attenuated but retained statistical significance after
      adjustment for indices of socioeconomic position across the life course.
      CONCLUSIONS: In this large cohort of Swedish men followed into middle age, IQ was
      related to very few of the cancer outcomes under investigation. This indicates
      that the recent observation that low IQ is related to increased mortality rates
      may not be generated by an IQ-cancer gradient. Given that the present analyses
      are among the first to examine these associations, replication is required.

PMID- 17220285
TI  - EGFR mutations in exons 18-21 in sporadic breast cancer.

PMID- 17220286
TI  - Early prediction of the long term evolution of multiple sclerosis: the Bayesian
      Risk Estimate for Multiple Sclerosis (BREMS) score.
AB  - AIM: To propose a simple tool for early prediction of unfavourable long term
      evolution of multiple sclerosis (MS). METHODS: A Bayesian model allowed us to
      calculate, within the first year of disease and for each patient, the Bayesian
      Risk Estimate for MS (BREMS) score that represents the risk of reaching secondary
      progression (SP). RESULTS: The median BREMS scores were higher in 158 patients
      who reached SP within 10 years compared with 1087 progression free patients (0.69
      vs 0.30; p<0.0001). The BREMS value was related to SP risk in the whole cohort
      (p<0.0001) and in the subgroup of 535 patients who had never been treated with
      immune therapies, thus reasonably representing the natural history of the disease
      (p<0.000001). CONCLUSIONS: The BREMS score may be useful both to identify
      patients who are candidates for early or for more aggressive therapies and to
      improve the design and analysis of clinical therapeutic trials and of
      observational studies.

PMID- 17220288
TI  - Human immunodeficiency virus associated intracranial aneurysms: report of three
      adult patients with an overview of the literature.
AB  - BACKGROUND AND PURPOSE: Aneurysms have been described in HIV infected patients.
      These involve predominantly extracranial blood vessels with specific histological
      and clinical features. Intracranial aneurysms are rare and have been identified
      mainly in children. METHODS: Case reports and literature review. RESULTS: Three
      black South African HIV positive adult patients with intracranial aneurysms were
      identified. The clinical, laboratory and radiological features are described.
      CONCLUSIONS: Intracranial aneurysms occur in both adults and children infected
      with HIV. More information is required on this association. The frequency in
      terms of numbers of cases indicates that it is an uncommon association or
      manifestation of HIV. The characteristics of the aneurysms suggest that they are
      distinctive and not a chance or coincidental co-occurrence of congenital or
      arteriosclerotic aneurysms.

PMID- 17220287
TI  - Accuracy of the bedside head impulse test in detecting vestibular hypofunction.
AB  - OBJECTIVE: To determine the accuracy of the bedside head impulse test (bHIT) by
      direct comparison with results from the quantitative head impulse test (qHIT) in
      the same subjects, and to investigate whether bHIT sensitivity and specificity
      changes with neuro-otological training. METHODS: Video clips of horizontal bHIT
      to both sides were produced in patients with unilateral and bilateral peripheral
      vestibular deficits (n = 15) and in healthy subjects (n = 9). For qHIT, eye and
      head movements were recorded with scleral search coils on the right eye and the
      forehead. Clinicians (neurologists or otolaryngologists) with at least 6 months
      of neuro-otological training ("experts": n = 12) or without this training ("non
      experts": n = 45) assessed video clips for ocular motor signs of vestibular
      deficits on either side or of normal vestibular function. RESULTS: On average,
      bHIT sensitivity was significantly (t test: p<0.05) lower for experts than for
      non-experts (63% vs 72%), while bHIT specificity was significantly higher for
      experts than non-experts (78% vs 64%). This outcome was a consequence of the
      experts' tendency to accept bHIT with corresponding borderline qHIT values as
      still being normal. Fitted curves revealed that at the lower normal limit of
      qHIT, 20% of bHIT were rated as deficient by the experts and 37% by the non
      experts. CONCLUSIONS: When qHIT is used as a reference, bHIT sensitivity is
      adequate and therefore clinically useful in the hands of both neuro-otological
      experts and non-experts. We advise performing quantitative head impulse testing
      with search coils or high speed video methods when bHIT is not conclusive.

PMID- 17220289
TI  - Carotid body autotransplantation in Parkinson disease: a clinical and positron
      emission tomography study.
AB  - BACKGROUND: Carotid body (CB) glomus cells are highly dopaminergic and express
      the glial cell line derived neurotrophic factor. The intrastriatal grafting of CB
      cell aggregates exerts neurotrophic actions on nigrostriatal neurons in animal
      models of Parkinson disease (PD). OBJECTIVE: We conducted a phase I-II clinical
      study to assess the feasibility, long term safety, clinical and neurochemical
      effects of intrastriatal CB autotransplantation in patients with PD. METHODS:
      Thirteen patients with advanced PD underwent bilateral stereotactic implantation
      of CB cell aggregates into the striatum. They were assessed before surgery and up
      to 1-3 years after surgery according to CAPIT (Core Assessment Programme for
      Intracerebral Transplantation) and CAPSIT-PD (Core Assessment Programme for
      Surgical Interventional Therapies in Parkinson's Disease) protocols. The primary
      outcome measure was the change in video blinded Unified Parkinson's Disease
      Rating Scale III score in the off-medication state. Seven patients had 18F-dopa
      positron emission tomography scans before and 1 year after transplantation.
      RESULTS: Clinical amelioration in the primary outcome measure was observed in 10
      of 12 blindly analysed patients, which was maximal at 6-12 months after
      transplantation (5-74%). Overall, mean improvement at 6 months was 23%. In the
      long term (3 years), 3 of 6 patients still maintained improvement (15-48%). None
      of the patients developed off-period dyskinesias. The main predictive factors for
      motor improvement were the histological integrity of the CB and a milder disease
      severity. We observed a non-significant 5% increase in mean putaminal 18F-dopa
      uptake but there was an inverse relationship between clinical amelioration and
      annual decline in putaminal 18F-dopa uptake (r = -0.829; p = 0.042). CONCLUSIONS:
      CB autotransplantation may induce clinical effects in patients with advanced PD
      which seem partly related to the biological properties of the implanted glomus
      cells.

PMID- 17220290
TI  - Risk factors for acute ischaemic stroke in young adults in South India.
AB  - BACKGROUND: Stroke is a leading cause of death and disability in developing
      countries, afflicting individuals at a young age. The contribution of established
      vascular risk factors to ischaemic stroke in young adults has not been evaluated
      systematically in Indians. METHODS: We conducted a case control study in 214
      South Indian patients with first acute ischaemic stroke that occurred between the
      ages of 15 and 45 years, 99 age and sex matched hospital controls and 96
      community controls. We compared the prevalence of the following risk factors:
      smoking, elevated blood pressure, high fasting blood glucose and abnormal lipids.
      RESULTS: Compared with community controls, stroke patients had a higher
      prevalence of smoking (multivariable adjusted odds ratio (OR) 7.77, 95% CI 1.93
      to 31.27), higher systolic blood pressure (OR per SD increment of 1.88, 95% CI
      1.01 to 3.49) and fasting blood glucose (OR per SD increment of 4.55, 95% CI 1.63
      to 12.67), but lower high density lipoprotein (HDL) cholesterol (OR per SD
      increment of 0.17, 95% CI 0.09 to 0.30). Compared with hospital controls, stroke
      patients had a higher prevalence of smoking (OR 3.95, 95% CI 1.61 to 9.71) and
      lower HDL cholesterol (OR per SD increment 0.27, 95% CI 0.17 to 0.44). The
      presence of > or = 3 metabolic syndrome components was associated strongly with
      stroke (OR 4.76, 95% CI 1.93 to 11.76; OR 2.09, 95% CI 1.06 to 4.13) compared
      with community and hospital controls. CONCLUSIONS: Key components of the
      metabolic syndrome and smoking are associated with ischaemic stroke in young
      South Indian adults. Our observations underscore the importance of targeting
      adolescents and young adults for screening and prevention to reduce the burden of
      ischaemic stroke in young adults.

PMID- 17220291
TI  - Cervical dystonia in spinocerebellar ataxia type 2: clinical and polymyographic
      findings.
AB  - Eighteen patients from three large multigenerational families with genetically
      established spinocerebellar ataxia type 2 (SCA2) were examined, with special
      attention to the presence of dystonic features. Cervical dystonia (CD) was
      diagnosed according to standardised clinical criteria. CD was scored using the
      Tsui score. Polymyography was performed in six cases using bilateral surface
      electrode recordings of the sternocleidomastoid and trapezius muscles together
      with needle electrode recordings of the splenius capitis muscles bilaterally. CD
      was found in 11 of 18 patients (61%), and was the presenting symptom in one case.
      Severity of CD was mild to moderate, with Tsui scores ranging from 5 to 12
      points. Polymyography in 6 of 11 SCA2 patients with CD showed the typical pattern
      of dystonia with spontaneous, involuntary muscle activation at rest in at least
      one neck muscle with disturbed reciprocal inhibition of antagonistic neck
      muscles. CD appears to be a common clinical feature in SCA2 and may precede
      ataxia and gait disturbance. By contrast, none of the 18 patients had dystonic
      features in other body regions. CD has probably been underreported in patients
      with the ataxic SCA2 phenotype and should be considered as an additional clinical
      manifestation in patients with hereditary ataxia.

PMID- 17220292
TI  - Clinicoradiological features of tuberculous meningitis in patients over 50 years
      of age.
AB  - BACKGROUND AND AIMS: Tuberculous meningitis (TBM) is a debilitating form of CNS
      tuberculosis with a high morbidity and mortality in spite of treatment. The
      diagnosis is based on clinical, radiological and laboratory features. The
      classical CT features of basal exudates, hydrocephalus, infarcts and granulomas
      have been mostly reported in younger individuals. Our aim was to study imaging
      features of TB meningitis in adults over the age of 50 years. MATERIALS AND
      METHODS: Clinical, imaging and laboratory features of 53 adult patients over the
      age of 50 years (sixth to eighth decades) were studied retrospectively. Diagnosis
      of TBM was based on clinical and laboratory features. RESULTS: Imaging features
      were the conspicuous absence of typical features of TBM (ie, basal meningeal
      enhancement, hydrocephalus, infarcts/granulomas were seen in only a minority of
      patients). CONCLUSIONS: CT features of TBM in elderly patients were few, atypical
      and non-contributory for diagnosis, probably because of age related immune
      senescence. Strong clinical suspicion and correlation with laboratory findings is
      necessary for early diagnosis.

PMID- 17220293
TI  - Polymorphisms of the renin-angiotensin system are associated with blood pressure,
      atherosclerosis and cerebral white matter pathology.
AB  - BACKGROUND: The renin-angiotensin system is involved in the development of
      hypertension, atherosclerosis and cardiovascular disease. We studied the
      association between the M235T polymorphism of the angiotensinogen gene (AGT) and
      the C573T polymorphism of the angiotensin II type 1 receptor (AT1R) and blood
      pressure, carotid atherosclerosis and cerebrovascular disease. METHODS: We
      genotyped over 6000 subjects from the Rotterdam Study and more than 1000 subjects
      from the Rotterdam Scan Study. We used logistic regression and univariate
      analyses, adjusting for age and sex with, for AGT, the MM and, for AT1R, the TT
      genotype as reference. RESULTS: We found that AGT-235T increased systolic (p for
      trend = 0.03) and diastolic blood pressure (p for trend = 0.04). The prevalence
      of carotid plaques was increased 1.25-fold (95% CI 1.02-1.52) in AGT-TT carriers.
      There was a significant increase in mean volume deep subcortical white matter
      lesions (WML) for AGT-TT carriers (1.78 ml vs 1.09 ml in the reference group; p =
      0.008). A significant interaction was found between AGT and AT1R, further
      increasing the effect on periventricular and subtotal WML (p for interaction =
      0.02). We found a non-significant increased risk of silent brain infarction for
      AGT-TT carriers and AT1R-CC carriers, but no effect on stroke. CONCLUSION: We
      found an association between AGT and blood pressure, atherosclerosis and WML.
      Also, we found synergistic effects between AGT and AT1R on the development of
      WML. These findings raise the question of whether the renin-angiotensin system
      may be a therapeutic target for the prevention of cerebral white matter
      pathology.

PMID- 17220294
TI  - The risk of recurrent stroke after intracerebral haemorrhage.
AB  - BACKGROUND AND AIM: The risks of recurrent intracerebral haemorrhage (ICH) vary
      widely (0-24%). Patients with ICH also have risk factors for ischaemic stroke
      (IS) and a proportion of ICH survivors re-present with an IS. This dilemma has
      implications for prophylactic treatment. This study aims to determine the risk of
      recurrent stroke events (both ICH and IS) following an index bleed and whether
      ICH recurrence risk varies according to location of index bleed. PATIENTS AND
      METHODS: All patients diagnosed with an acute ICH presenting over an 8.5 year
      period were identified. Each ICH was confirmed by reviewing all of the radiology
      results and, where necessary, the clinical case notes or post-mortem data.
      Recurrent stroke events (ICH and IS) were identified by reappearance of these
      patients in our stroke database. Coronal post-mortem results for the same period
      were also reviewed. Each recurrent event was reviewed to confirm the diagnosis
      and location of the stroke. RESULTS: Of the 7686 stroke events recorded, 768
      (10%) were ICH. In the follow-up period, there were 19 recurrent ICH and 17 new
      IS in the 464 patients who survived beyond the index hospital stay. Recurrence
      rate for ICH was 2.1/100 in the first year but 1.2/100/year overall. This
      compares with 1.3/100/year overall for IS. Most recurrences were "lobar-lobar"
      type. CONCLUSION: The cumulative risk of recurrent ICH in this population is
      similar to that of IS after the first year.

PMID- 17220295
TI  - Clostridium difficile toxin B causes apoptosis in epithelial cells by thrilling
      mitochondria. Involvement of ATP-sensitive mitochondrial potassium channels.
AB  - Targeting to mitochondria is emerging as a common strategy that bacteria utilize
      to interact with these central executioners of apoptosis. Several lines of
      evidence have in fact indicated mitochondria as specific targets for bacterial
      protein toxins, regarded as the principal virulence factors of pathogenic
      bacteria. This work shows, for the first time, the ability of the Clostridium
      difficile toxin B (TcdB), a glucosyltransferase that inhibits the Rho GTPases, to
      impact mitochondria. In living cells, TcdB provokes an early hyperpolarization of
      mitochondria that follows a calcium-associated signaling pathway and precedes the
      final execution step of apoptosis (i.e. mitochondria depolarization).
      Importantly, in isolated mitochondria, the toxin can induce a calcium-dependent
      mitochondrial swelling, accompanied by the release of the proapoptogenic factor
      cytochrome c. This is consistent with a mitochondrial targeting that does not
      require the Rho-inhibiting activity of the toxin. Of interest, the mitochondrial
      ATP-sensitive potassium channels are also involved in the apoptotic response to
      TcdB and appear to be crucial for the cell death execution phase, as demonstrated
      by using specific modulators of these channels. To our knowledge, the involvement
      of these mitochondrial channels in the ability of a bacterial toxin to control
      cell fate is a hitherto unreported finding.

PMID- 17220296
TI  - Structure-function analysis of the cuprous oxidase activity in Fet3p from
      Saccharomyces cerevisiae.
AB  - The Fet3 protein from Saccharomyces cerevisiae is a multicopper oxidase with
      specificity toward Fe(II) and Cu(I). Fet3p turnover of Fe(II) supports high
      affinity iron uptake across the yeast plasma membrane, whereas its turnover of
      Cu(I) contributes to copper resistance in yeast. The structure of Fet3p has been
      used to identify possible amino acid residues responsible for this protein's
      reactivity with Cu(I), and structure-function analyses have confirmed this
      assignment. Fet3p Met(345) is required for the enzyme's reactivity toward Cu(I).
      Although the Fet3pM345A mutant exhibits wild type spectral and electrochemical
      behavior, the kinetic constants for Cu(I) turnover and for single-turnover
      electron transfer from Cu(I) to the enzyme are significantly reduced. The
      specificity constant with Cu(I) as substrate is reduced by one-fifth, whereas the
      electron transfer rate from Cu(I) is reduced 50-fold. This mutation has little
      effect on the reactivity toward Fe(II), indicating that Met(345) contributes
      specifically to Fet3p reactivity with the cuprous ion. These kinetic defects
      render the Fet3pM345A unable to support wild type cellular copper resistance,
      suggesting that there is a finely tuned copper redox balance at the yeast plasma
      membrane.

PMID- 17220297
TI  - Tumor necrosis factor receptor 2 signaling induces selective c-IAP1-dependent
      ASK1 ubiquitination and terminates mitogen-activated protein kinase signaling.
AB  - TRAF2 and ASK1 play essential roles in tumor necrosis factor alpha (TNF-alpha)
      induced mitogen-activated protein kinase signaling. Stimulation through TNF
      receptor 2 (TNFR2) leads to TRAF2 ubiquitination and subsequent proteasomal
      degradation. Here we show that TNFR2 signaling also leads to selective ASK1
      ubiquitination and degradation in proteasomes. c-IAP1 was identified as the
      ubiquitin protein ligase for ASK1 ubiquitination, and studies with primary B
      cells from c-IAP1 knock-out animals revealed that c-IAP1 is required for TNFR2
      induced TRAF2 and ASK1 degradation. Moreover, in the absence of c-IAP1 TNFR2
      mediated p38 and JNK activation was prolonged. Thus, the ubiquitin protein ligase
      activity of c-IAP1 is responsible for regulating the duration of TNF signaling in
      primary cells expressing TNFR2.

PMID- 17220298
TI  - The luminal Vps10p domain of sortilin plays the predominant role in targeting to
      insulin-responsive Glut4-containing vesicles.
AB  - In fat and skeletal muscle cells, insulin-responsive vesicles, or IRVs, deliver
      glucose transporter Glut4 and several associated proteins to the plasma membrane
      in response to hormonal stimulation. Although the protein composition of the IRVs
      is well studied, the mechanism of their formation is unknown. It is believed,
      however, that the cytoplasmic tails of the IRV component proteins carry targeting
      information to this compartment. To test this hypothesis, we have studied
      targeting of sortilin, one of the major IRV constituents. We have found that the
      reporter protein consisting of the cytoplasmic tail of sortilin and EGFP is co
      localized with ectopically expressed Glut4 in the perinuclear compartment of
      undifferentiated 3T3-L1 cells that do not form insulin-responsive vesicles. Upon
      cell differentiation, this reporter protein does not enter the IRVs; moreover, it
      loses its perinuclear localization and becomes randomly distributed throughout
      the whole intracellular space. In contrast, the tagged luminal Vps10p domain of
      sortilin demonstrates partial co-localization with Glut4 in both undifferentiated
      and differentiated cells and is targeted to the IRVs upon cell differentiation.
      Using chemical cross-linking and the yeast two-hybrid system, we show that
      sortilin interacts with Glut4 and IRAP in the vesicular lumen. Our results
      suggest that luminal interactions between component proteins play an important
      role in the process of IRV biogenesis.

PMID- 17220299
TI  - Thioredoxin 1 and thioredoxin 2 have opposed regulatory functions on hypoxia
      inducible factor-1alpha.
AB  - Hypoxia inducible factor 1 (HIF-1), a key regulator for adaptation to hypoxia, is
      composed of HIF-1alpha and HIF-1beta. In this study, we present evidence that
      overexpression of mitochondria-located thioredoxin 2 (Trx2) attenuated hypoxia
      evoked HIF-1alpha accumulation, whereas cytosolic thioredoxin 1 (Trx1) enhanced
      HIF-1alpha protein amount. Transactivation of HIF-1 is decreased by
      overexpression of Trx2 but stimulated by Trx1. Inhibition of proteasomal
      degradation of HIF-1alpha in Trx2-overexpressing cells did not fully restore HIF
      1alpha protein levels, while HIF-1alpha accumulation was enhanced in Trx1
      overexpressing cells. Reporter assays showed that cap-dependent translation is
      increased by Trx1 and decreased by Trx2, whereas HIF-1alpha mRNA levels remained
      unaltered. These data suggest that thioredoxins affect the synthesis of HIF
      1alpha. Trx1 facilitated synthesis of HIF-1alpha by activating Akt, p70S6K, and
      eIF-4E, known to control cap-dependent translation. In contrast, Trx2 attenuated
      activities of Akt, p70S6K, and eIF-4E and provoked an increase in mitochondrial
      reactive oxygen species production. MitoQ, a mitochondria specific antioxidant,
      reversed HIF-1alpha accumulation as well as Akt activation under hypoxia in Trx2
      cells, supporting the notion of translation control mechanisms in affecting HIF
      1alpha protein accumulation.

PMID- 17220300
TI  - Regulation of s6 kinase 1 activation by phosphorylation at ser-411.
AB  - Ribosomal S6 kinase 1 (S6K1), as a key regulator of mRNA translation, plays an
      important role in cell cycle progression through the G(1) phase of proliferating
      cells and in the synaptic plasticity of terminally differentiated neurons.
      Activation of S6K1 involves the phosphorylation of its multiple Ser/Thr residues,
      including the proline-directed sites (Ser-411, Ser-418, Thr-421, and Ser-424) in
      the autoinhibitory domain near the C terminus. Phosphorylation at Thr-389 is also
      a crucial event in S6K1 activation. Here, we report that S6K1 phosphorylation at
      Ser-411 is required for the rapamycin-sensitive phosphorylation of Thr-389 and
      the subsequent activation of S6K1. Mutation of Ser-411 to Ala ablated insulin
      induced Thr-389 phosphorylation and S6K1 activation, whereas mutation mimicking
      Ser-411 phosphorylation did not show any effect. Furthermore, phosphomimetic
      mutation of Thr-389 overcame the inhibitory effect of the mutation S411A. Thus,
      Ser-411 phosphorylation regulates S6K1 activation via the control of Thr-389
      phosphorylation. In nervous system neurons, Cdk5-p35 kinase associates with S6K1
      via the direct interaction between p35 and S6K1 and catalyzes S6K1
      phosphorylation specifically at Ser-411. Inhibition of the Cdk5 activity or
      suppression of Cdk5 expression blocked S6K1 phosphorylation at Ser-411 and Thr
      389, resulting in S6K1 inactivation. Similar results were obtained by treating
      asynchronous populations of proliferating cells with the CDK inhibitor compound
      roscovitine. Altogether, our findings suggest a novel mechanism by which the CDK
      mediated phosphorylation regulates the activation of S6K1.

PMID- 17220301
TI  - The MicroRNA let-7a modulates interleukin-6-dependent STAT-3 survival signaling
      in malignant human cholangiocytes.
AB  - The inflammation-associated cytokine interleukin-6 (IL-6) can contribute to tumor
      growth and resistance to therapy by the activation of survival mechanisms. In
      several human cancers, IL-6-activated survival signaling involves the signal
      transducers and activators of transcription (Stat) factors or protein kinase
      cascades. microRNAs (miRNAs) are endogenous regulators of gene expression that
      are altered in expression in many cancers. However, the effect of inflammatory
      cytokines on miRNA expression and the role of miRNA in modulating IL-6-mediated
      cell survival are unknown. We investigated the involvement of miRNA in malignant
      cholangiocytes stably transfected to overexpress IL-6, which enhances tumor
      growth in vivo by inhibition of apoptosis. We provide evidence that (i) miRNA
      expression both in vitro and in vivo is altered by overexpression of IL-6; (ii)
      selective miRNAs including let-7a are up-regulated and contribute to the survival
      effects of enforced IL-6 activity; and (iii) let-7a contributes to the
      constitutively increased phosphorylation of Stat-3 by a mechanism involving the
      neurofibromatosis 2 (NF2) gene. These findings reveal a novel mechanism by which
      IL-6 mediates tumor cell survival that may be therapeutically targeted and
      emphasize the presence of complex interrelationships between deregulated
      expression of miRNA and transcription factors in human cancers.

PMID- 17220302
TI  - A novel role of the actin-nucleating Arp2/3 complex in the regulation of RNA
      polymerase II-dependent transcription.
AB  - It has been well documented that actin is present in the nucleus and involved in
      numerous nuclear functions including regulation of transcription. The actin
      nucleating Arp2/3 complex is an essential, evolutionarily conserved seven-subunit
      protein complex that promotes actin cytoskeleton assembly in the cytoplasm upon
      stimulation by WASP family proteins. Our recent study indicates that the nuclear
      localized neural Wiskott-Aldrich syndrome protein (N-WASP) can induce de novo
      actin polymerization in the nucleus, and this function is important for the role
      of N-WASP in the regulation of RNA polymerase II-dependent transcription. Here,
      we have presented evidence to show that the Arp2/3 complex is also localized in
      the nucleus and plays an essential role in mediating nuclear actin polymerization
      induced by N-WASP. We have also demonstrated that the Arp2/3 complex physically
      associates with RNA polymerase II and is involved in the RNA polymerase II
      dependent transcriptional regulation both in vivo and in vitro. Together, these
      data provide strong support for the hypothesis that N-WASP and the Arp2/3 complex
      regulate transcription, at least in part, through the regulation of nuclear actin
      polymerization in a manner similar to their function in the cytoplasm.

PMID- 17220303
TI  - Regulation of the transport and protein levels of the inositol phosphorylceramide
      mannosyltransferases Csg1 and Csh1 by the Ca2+-binding protein Csg2.
AB  - Complex sphingolipids in yeast are known to function in cellular adaptation to
      environmental changes. One of the yeast complex sphingolipids, mannosylinositol
      phosphorylceramide (MIPC), is produced by the redundant inositol
      phosphorylceramide (IPC) mannosyltransferases Csg1 and Csh1. The Ca2+-binding
      protein Csg2 can form a complex with either Csg1 or Csh1 and is considered to act
      as a regulatory subunit. However, the role of Csg2 in MIPC synthesis has remained
      unclear. In this study, we found that Csg1 and Csh1 are N-glycosylated with core
      type and mannan-type structures, respectively. Further identification of the
      glycosylated residues suggests that both Csg1 and Csh1 exhibit membrane topology
      with their C termini in the cytosol and their mannosyltransferase domains in the
      lumen. After complexing with Csg2, both Csg1 and Csh1 function in the Golgi, and
      then are delivered to the vacuole for degradation. However, uncomplexed Csh1
      cannot exit from the endoplasmic reticulum. We also demonstrated that Ca2+
      stimulates IPC-to-MIPC conversion, because of a Csg2-dependent increase in Csg1
      levels. Thus, Csg2 has several regulatory functions for Csg1 and Csh1, including
      stability, transport, and gene expression.

PMID- 17220304
TI  - Immunostimulatory properties of the emerging pathogen Stenotrophomonas
      maltophilia.
AB  - Stenotrophomonas maltophilia is a multiple-antibiotic-resistant opportunistic
      pathogen that is being isolated with increasing frequency from patients with
      health-care-associated infections and especially from patients with cystic
      fibrosis (CF). While clinicians feel compelled to treat infections involving this
      organism, its potential for virulence is not well established. We evaluated the
      immunostimulatory properties and overall virulence of clinical isolates of S.
      maltophilia using the well-characterized opportunistic pathogen Pseudomonas
      aeruginosa PAO1 as a control. The properties of CF isolates were examined
      specifically to see if they have a common phenotype. The immunostimulatory
      properties of S. maltophilia were studied in vitro by stimulating airway
      epithelial and macrophage cell lines. A neonatal mouse model of pneumonia was
      used to determine the rates of pneumonia, bacteremia, and mortality, as well as
      the inflammatory response elicited by S. maltophilia infection. Respiratory and
      nonrespiratory S. maltophilia isolates were highly immunostimulatory and elicited
      significant interleukin-8 expression by airway epithelial cells, as well as tumor
      necrosis factor alpha (TNF-alpha) expression by macrophages. TNF-alpha signaling
      appears to be important in the pathogenesis of S. maltophilia infection as less
      than 20% of TNFR1 null mice (compared with 100% of wild-type mice) developed
      pneumonia and bacteremia following intranasal inoculation. The S. maltophilia
      isolates were weakly invasive, and low-level bacteremia with no mortality was
      observed. Despite the lack of invasiveness of S. maltophilia, the
      immunostimulatory properties of this organism and its induction of TNF-alpha
      expression specifically indicate that it is likely to contribute significantly to
      airway inflammation.

PMID- 17220305
TI  - Pneumolysin, PspA, and PspC contribute to pneumococcal evasion of early innate
      immune responses during bacteremia in mice.
AB  - The pneumococcal virulence factors include capsule, PspA, PspC, and Ply.
      Cytometric analysis demonstrated that the greatest levels of C3 deposition were
      on a Deltaply PspA(-) PspC(-) mutant. Also, Ply, PspA, and PspC expression
      resulted in C3 degradation in vitro and in vivo. Finally, blood clearance assays
      demonstrated that there was enhanced clearance of Deltaply PspA(-) PspC(-)
      pneumococci compared to the clearance of nonencapsulated pneumococci.

PMID- 17220306
TI  - Interleukin-12 drives the Th1 signaling pathway in Helicobacter pylori-infected
      human gastric mucosa.
AB  - In this study we examined mechanisms that regulate T-helper lymphocyte 1 (Th1)
      commitment in Helicobacter pylori-infected human gastric mucosa. The levels of
      gamma interferon (IFN-gamma), interleukin-4 (IL-4), and IL-12 in total extracts
      of gastric biopsies taken from H. pylori-infected and uninfected patients were
      determined by an enzyme-linked immunosorbent assay. The levels of signal
      transducer and activator of transcription 4 (STAT4), STAT6, and T-box expressed
      in T cells (T-bet) in total proteins extracted from gastric biopsies were
      determined by Western blotting. Finally, the effect of a neutralizing IL-12
      antibody on expression of Th1 transcription factors and the levels of IFN-gamma
      in organ cultures of H. pylori-infected biopsies was examined. Increased levels
      of IFN-gamma and IL-12 were found in gastric biopsy samples of H. pylori-infected
      patients compared to the levels in uninfected patients. In addition, H. pylori
      infected biopsies exhibited high levels of expression of phosphorylated STAT4 and
      T-bet. Higher levels of IFN-gamma and expression of Th1 transcription factors
      were associated with greater infiltration of mononuclear cells in the gastric
      mucosa. By contrast, production of IL-4 and expression of phosphorylated STAT6
      were not associated with the intensity of mononuclear cell infiltration. In ex
      vivo organ cultures of H. pylori-infected biopsies, neutralization of endogenous
      IL-12 down-regulated the expression of phosphorylated STAT4 and T-bet and reduced
      IFN-gamma production. Our data indicated that IL-12 contributes to the Th1 cell
      commitment in H. pylori-infected human gastric mucosa.

PMID- 17220307
TI  - Native microbial colonization of Drosophila melanogaster and its use as a model
      of Enterococcus faecalis pathogenesis.
AB  - Enterococci are commensal organisms of the gastrointestinal (GI) tracts of a
      broad range of mammalian and insect hosts, but they are also leading causes of
      nosocomial infection. Little is known about the ecological role of enterococci in
      the GI tract consortia. To develop a tractable model for studying the roles of
      these organisms as commensals and pathogens, we characterized the Drosophila
      melanogaster microflora and examined the occurrence of enterococci in the
      gastrointestinal consortium of Drosophila. In a survey of laboratory-reared
      Drosophila and wild-captured flies, we found that Drosophila was naturally
      colonized by representatives of five bacterial phyla. Among these organisms were
      several species of enterococci, including Enterococcus faecalis, Enterococcus
      faecium, Enterococcus gallinaraum, and Enterococcus durans, as well as a
      previously detected but uncultured Enterococcus species. Drosophila could be
      cured of enterococcal carriage by antibiotic treatment and could be reassociated
      with laboratory strains. High-level colonization by a well-characterized strain
      expressing the enterococcal cytolysin was found to be detrimental to Drosophila
      compared to the effect of an isogenic, noncytolytic control. The anatomical
      distribution of enterococci in the Drosophila GI tract was determined by
      immunohistochemical staining of thin sections of naturally colonized and
      reassociated flies.

PMID- 17220308
TI  - Surfactant protein A2 (SP-A2) variants expressed in CHO cells stimulate
      phagocytosis of Pseudomonas aeruginosa more than do SP-A1 variants.
AB  - Surfactant protein A (SP-A) enhances phagocytosis of Pseudomonas aeruginosa. Two
      functional genes, SP-A1 and SP-A2, encode human SP-A. As we showed before,
      baculovirus-mediated insect cell-expressed SP-A2 enhances the association of P.
      aeruginosa with rat alveolar macrophages (rAMs) more than does SP-A1. However,
      true phagocytosis (internalization) was not shown, and insect cell derived
      proteins lack or are defective in certain mammalian posttranslational
      modifications that may be important for SP-A1 and SP-A2 activity and specificity.
      Here we used SP-A1 (6A(2), 6A(4)) and SP-A2 (1A(0), 1A(1)) allele variants
      expressed by CHO (Chinese hamster ovary) mammalian cells to study their effect on
      association and/or internalization of P. aeruginosa by rAMs and/or human AMs
      (hAMs) and to study if phagocytosis can be modulated differentially and/or more
      effectively by CHO cell-expressed SP-A variants than by insect-cell expressed SP
      A variants. For cell association and internalization assessments, light
      microscopy and fluorescence-activated cell sorter analyses were used,
      respectively. We found the following for the first time. (i) SP-A2 variants
      enhanced phagocytosis (cell association and/or internalization) of P. aeruginosa
      more than SP-A1 variants did, and the cell association correlated with
      internalization. (ii) Differences in the activities of SP-A variants were
      observed in the following order: 1A(1)>1A(0)>6A(2)>6A(4). (iii) rAMs, although
      more active than hAMs, are an appropriate model, as SP-A2 variants exhibited
      activity higher than that seen for SP-A1 variants with either rAMs or hAMs. (iv)
      CHO cell-expressed SP-A was considerably more active than insect cell-expressed
      variants. We conclude that SP-A2 variants stimulate phagocytosis of P. aeruginosa
      more effectively than SP-A1 variants and that posttranslational modifications
      positively influence the phagocytic activity of SP-A.

PMID- 17220309
TI  - Pneumococcal capsular polysaccharide vaccine-mediated protection against serotype
      3 Streptococcus pneumoniae in immunodeficient mice.
AB  - Pneumococcal capsular polysaccharide (PPS) vaccines are less immunogenic in
      immunocompromised than immunocompetent individuals. However, neither the efficacy
      of PPS vaccines in immunocompromised individuals nor the host cellular subsets
      required for vaccine efficacy against pneumococcal disease have been directly
      investigated. In this study, we vaccinated CD4-deficient (CD4(-/-)), CD8
      deficient (CD8(-/-)), and secretory immunoglobulin M-deficient (sIgM(-/-)) mice
      and wild-type C57BL/6 (Wt) mice with a conjugate of PPS of serotype 3 and tetanus
      toxoid (PPS3-TT) and determined the antibody response and efficacy of vaccination
      against systemic and pulmonary challenge with serotype 3 pneumococcus in
      immunized and control mice. Our results showed that the isotype and predominant
      IgG subclass of the PPS3 response differed between immunodeficient mouse strains
      and between immunodeficient and Wt mice, with CD8(-/-) mice having the most
      robust response. Vaccination protected Wt, CD4(-/-), and sIgM(-/-) mice from
      death resulting from both systemic and pulmonary challenge, whereas CD8(-/-) mice
      were protected only from systemic and not from pulmonary challenge. Passive
      vaccination with PPS3-TT-induced sera from Wt, CD4(-/-), CD8(-/-), and sIgM(-/-)
      mice protected naive Wt mice from death due to pulmonary challenge; however, CD8(
      /-) mice were not protected by sera from Wt or CD8(-/-) mice. Our findings
      suggest that PPS-based vaccines can be effective in the setting of CD4 T-cell
      deficiency but that CD8 T cells could be required for vaccine-mediated protection
      against pulmonary challenge with serotype 3 pneumococcus.

PMID- 17220311
TI  - Potential role for Toll-like receptor 4 in mediating Escherichia coli maltose
      binding protein activation of dendritic cells.
AB  - The Escherichia coli maltose-binding protein (MBP) is used to increase the
      stability and solubility of proteins in bacterial protein expression systems and
      is increasingly being used to facilitate the production and delivery of subunit
      vaccines against various pathogenic bacteria and viruses. The MBP tag is presumed
      inert, with minimum effects on the bioactivity of the tagged protein or its
      biodistribution. However, few studies have characterized the immunological
      attributes of MBP. Here, we analyze the phenotypic and functional outcomes of MBP
      treated dendritic cells (DCs) and show that MBP induces DC activation and
      production of proinflammatory cytokines (interleukin-1beta [IL-1beta], IL-6, IL
      8, tumor necrosis factor alpha, and IL-12p70) within 24 h and strongly increases
      Ikappabeta phosphorylation in treated cells. Interestingly, phosphorylation of
      Ikappabeta was largely abrogated by the addition of anti-human Toll-like receptor
      4 (TLR4) antibodies, indicating that MBP activates signaling for DC maturation
      via TLR4. Consistent with this hypothesis, MBP activated the TLR4-expressing cell
      line 293-hTLR4A but not control cultures to secrete IL-8. The observed data were
      independent of lipopolysaccharide contamination and support a role for TLR4 in
      mediating the effects of MBP. These results provide insight into a mechanism by
      which MBP might enhance immune responses to vaccine fusion proteins.

PMID- 17220310
TI  - Burkholderia cenocepacia requires a periplasmic HtrA protease for growth under
      thermal and osmotic stress and for survival in vivo.
AB  - Burkholderia cenocepacia, a member of the B. cepacia complex, is an opportunistic
      pathogen that causes serious infections in patients with cystic fibrosis. We
      identified a six-gene cluster in chromosome 1 encoding a two-component regulatory
      system (BCAL2831 and BCAL2830) and an HtrA protease (BCAL2829) hypothesized to
      play a role in the B. cenocepacia stress response. Reverse transcriptase PCR
      analysis of these six genes confirmed they are cotranscribed and comprise an
      operon. Genes in this operon, including htrA, were insertionally inactivated by
      recombination with a newly created suicide plasmid, pGPOmegaTp. Genetic analyses
      and complementation studies revealed that HtrA(BCAL2829) was required for growth
      of B. cenocepacia upon exposure to osmotic stress (NaCl or KCl) and thermal
      stress (44 degrees C). In addition, replacement of the serine residue in the
      active site with alanine (S245A) and deletion of the HtrA(BCAL2829) PDZ domains
      demonstrated that these areas are required for protein function. HtrA(BCAL2829)
      also localizes to the periplasmic compartment, as shown by Western blot analysis
      and a colicin V reporter assay. Using the rat agar bead model of chronic lung
      infection, we also demonstrated that inactivation of the htrA gene is associated
      with a bacterial survival defect in vivo. Together, our data demonstrate that
      HtrA(BCAL2829) is a virulence factor in B. cenocepacia.

PMID- 17220312
TI  - Yersiniabactin is a virulence factor for Klebsiella pneumoniae during pulmonary
      infection.
AB  - Iron acquisition systems are essential for the in vivo growth of bacterial
      pathogens. Despite the epidemiological importance of Klebsiella pneumoniae, few
      experiments have examined the importance of siderophores in the pathogenesis of
      this species. A previously reported signature-tagged mutagenesis screen
      identified an attenuated strain that featured an insertional disruption in ybtQ,
      which encodes a transporter for the siderophore yersiniabactin. We used this
      finding as a starting point to evaluate the importance of siderophores in the
      physiology and pathogenesis of K. pneumoniae. Isogenic strains carrying in-frame
      deletions in genes required for the synthesis of either enterobactin or
      yersiniabactin were constructed, and the growth of these mutants was examined
      both in vitro and in vivo using an intranasal infection model. The results
      suggest divergent functions for each siderophore in different environments, with
      enterobactin being more important for growth in vitro under iron limitation than
      in vivo and the reverse being true for the yersiniabactin locus. These
      observations represent the first examination of isogenic mutants in iron
      acquisition systems for K. pneumoniae and may indicate that the acquisition of
      nonenterobactin siderophores is an important step in the evolution of virulent
      enterobacterial strains.

PMID- 17220314
TI  - Role of unsaturated fatty acid biosynthesis in virulence of Streptococcus mutans.
AB  - An insertionally inactivated fabM strain of Streptococcus mutans does not produce
      unsaturated membrane fatty acids and is acid sensitive (E. M. Fozo and R. G.
      Quivey, Jr., J. Bacteriol. 186:4152-4158, 2004). In this study, the strain was
      shown to be poorly transmissible from host to host. Animals directly infected
      with the fabM strain exhibited fewer and less severe carious lesions than those
      observed in the wild-type strain.

PMID- 17220313
TI  - SiiE is secreted by the Salmonella enterica serovar Typhimurium pathogenicity
      island 4-encoded secretion system and contributes to intestinal colonization in
      cattle.
AB  - Here we report that Salmonella enterica serovar Typhimurium pathogenicity island
      4 carries a type I secretion system (siiCDF) which secretes an approximately 600
      kDa protein (encoded by siiE). SiiE is surface expressed, and its production is
      regulated by HilA. SiiE and SiiF influence colonization in cattle and the
      invasion of bovine enterocytes.

PMID- 17220315
TI  - Kgp and RgpB, but not RgpA, are important for Porphyromonas gingivalis virulence
      in the murine periodontitis model.
AB  - The contributions of three proteinase genes (rgpA, rgpB, and kgp) to the
      virulence of Porphyromonas gingivalis W50 were investigated in the murine
      periodontitis model. Mice were orally inoculated with eight doses (1 x 10(10)
      cells per dose) of rgpA, rgpB, kgp, rgpA rgpB, or rgpA rgpB kgp isogenic mutants,
      and the level of alveolar bone loss, immune response induced, and number of
      bacterial cells per half maxilla were compared with those of animals inoculated
      with wild-type P. gingivalis. The kgp, rgpB, rgpA rgpB, and rgpA rgpB kgp
      isogenic mutants induced significantly (P < 0.05) less bone loss than the rgpA
      isogenic mutant and the wild type did, and the virulence of the rgpA isogenic
      mutant and the wild type were not significantly different. Mice inoculated with
      the wild type or the rgpA isogenic mutant exhibited significantly (P < 0.01) more
      P. gingivalis cells per half maxilla than mice inoculated with rgpB, kgp, rgpA
      rgpB, and rgpA rgpB kgp isogenic mutants or nonchallenged mice did, as determined
      using real-time PCR. A significant positive correlation was found between the
      number of P. gingivalis cells detected per half maxilla and the amount of
      alveolar bone loss induced. Enzyme-linked immunosorbent assay results showed that
      each isogenic mutant and the wild type induced a predominant P. gingivalis
      antigen-specific immunoglobulin G3 (IgG3) response. Furthermore, the kgp and rgpA
      rgpB kgp isogenic mutants induced significantly (P < 0.05) lower IgG3 antibody
      responses than the responses induced by the wild type or the rgpA, rgpB, and rgpA
      rgpB isogenic mutants. The results suggest that the order in which the
      proteinases contribute to the virulence of P. gingivalis in the murine
      periodontitis model is Kgp > or = RgpB >> RgpA.

PMID- 17220316
TI  - A UspA2H-negative variant of Moraxella catarrhalis strain O46E has a deletion in
      a homopolymeric nucleotide repeat common to uspA2H genes.
AB  - Moraxella catarrhalis strains can express either a UspA2 protein or a UspA2H
      protein. The latter protein is encoded by a gene that possesses a homopolymeric
      nucleotide tract containing eight adenine (A) residues [i.e., a poly(A) tract]
      which is located near the 5' end. A spontaneous UspA2H-negative variant of M.
      catarrhalis strain O46E, designated O46E.U2V, was found to have a uspA2H poly(A)
      tract that contained seven A residues. Northern blot analysis of total RNA from
      the O46E parent strain revealed a readily detectable uspA2H mRNA transcript,
      whereas little or no uspA2H transcript was detectable in total RNA from the
      UspA2H-negative variant O46E.U2V. The 5' end of the uspA2H genes from both the
      O46E parent strain and the O46E.U2V variant were ligated to a promoterless lacZ
      gene to prepare translational fusions for use as reporter constructs. The level
      of beta-galactosidase activity expressed by the fusion construct containing eight
      A residues in its poly(A) tract was 200-fold greater than that obtained with the
      construct that had seven A residues. Site-directed mutagenesis of the 5' end of
      the uspA2H gene confirmed that translation was initiated at a GTG codon located
      21 nucleotides (nt) upstream of the poly(A) tract. Primer extension analysis
      determined that the transcriptional start site of the uspA2H gene was located 291
      nt upstream from the GTG translational start codon. This poly(A) tract was also
      found to be present in the uspA2H genes of other M. catarrhalis strains.

PMID- 17220317
TI  - Human immunoglobulin G2 (IgG2) and IgG4, but not IgG1 or IgG3, protect mice
      against Cryptococcus neoformans infection.
AB  - The encapsulated yeast Cryptococcus neoformans is a significant cause of
      meningitis and death in patients with AIDS. Some murine monoclonal antibodies
      (MAbs) against the glucuronoxylomannan (GXM) component of the C. neoformans
      capsular polysaccharide can prolong the lives of infected mice, while others have
      no effect or can even shorten survival. To date, no one has systematically
      compared the efficacies of antibodies with the same variable regions and
      different human constant regions with their unique combination of effector
      functions in providing protection against murine C. neoformans infection. In the
      present study, we examined the efficacies of anti-GXM MAbs of the four human
      immunoglobulin G (IgG) subclasses, which have identical variable regions but
      differ in their capacities to bind the three types of Fc receptors for IgG
      (FcgammaR), their abilities to activate complement, and their half-lives. IgG2
      and IgG4 anti-GXM prolonged the lives of infected BALB/c mice, IgG3 anti-GXM did
      not affect animal survival, while mice treated with IgG1 anti-GXM died earlier
      than mice treated with phosphate-buffered saline or irrelevant isotype-matched
      MAbs. All MAbs decreased serum GXM in infected animals. Effector pathways
      traditionally believed to be important in defense against microbes, such as
      opsonophagocytosis and complement binding, negatively correlated with antibody
      efficacy. It is generally accepted that human IgG1 has the most favorable
      combination of effector functions for therapeutic use against infections.
      Therefore, our findings have significant implications for humanization of the
      mouse IgG1 currently in clinical trials for cryptococcal meningitis and for the
      design of antibody therapeutics to treat other infectious diseases as well.

PMID- 17220319
TI  - Evidence for distinctive mechanisms of S-nitrosoglutathione metabolism by AdhC in
      two closely related species, Neisseria gonorrhoeae and Neisseria meningitidis.
AB  - The adhC gene from 11 strains of Neisseria gonorrhoeae was distinguished from its
      homologue in Neisseria meningitidis by the presence of a premature stop codon
      caused by a single base insertion. Mutational analysis showed that NADH S
      nitrosoglutathione oxidoreductase activity was associated with adhC in Neisseria
      meningitidis but not in Neisseria gonorrhoeae.

PMID- 17220318
TI  - In vitro induction of immunoglobulin A (IgA)- and IgM-secreting plasma blasts by
      cholera toxin depends on T-cell help and is mediated by CD154 up-regulation and
      inhibition of gamma interferon synthesis.
AB  - Cholera toxin (CT) and the type II heat-labile enterotoxins (LT-IIa and LT-IIb)
      are potent immunological adjuvants which are hypothesized to enhance the
      production of antibody (Ab)-secreting cells, although their mechanisms of action
      are not fully understood. The treatment of splenic cells with concanavalin A
      (ConA) plus CT enhanced the production of immunoglobulin A (IgA) and IgM by
      dividing cells that expressed high levels of major histocompatibility complex
      class II (MHC-II), CD19, and CD138 and low levels of B220 a phenotype
      characteristic of plasma blasts. LT-IIa or LT-IIb moderately enhanced IgA and IgM
      production without enhancing plasma blast differentiation. CT up-regulated CD25,
      CD69, CD80, CD86, and MHC-II in isolated B cells but failed to induce
      proliferation or differentiation. The treatment of unfractionated splenic cells
      with ConA plus CT induced B-cell proliferation and differentiation, but the
      elimination of CD4(+) T cells inhibited this effect. CT treatment of ConA
      activated CD4(+) T cells up-regulated CD134 and CD154, whereas the blockage of
      CD40-CD154 interactions inhibited the induction of plasma blasts and Ig
      synthesis. The treatment of unfractionated splenic cells with CT, LT-IIa, or LT
      IIb enhanced the production of interleukin-6 (IL-6) and IL-10, whereas the
      production of gamma interferon was inhibited in both CD4(+) and CD8(+) T cells
      mostly by CT. Thus, major regulatory effects of CT on lymphocytes are likely
      exerted early during the induction of immune responses when B and T cells
      initially encounter antigen. Neither LT-IIa or LT-IIb had these effects,
      indicating that type II enterotoxins augment Ab responses by other mechanisms.

PMID- 17220320
TI  - Monocyte chemoattractant protein 1, macrophage inflammatory protein 1 alpha, and
      RANTES recruit macrophages to the kidney in a mouse model of hemolytic-uremic
      syndrome.
AB  - The macrophage has previously been implicated in contributing to the renal
      inflammation associated with hemolytic-uremic syndrome (HUS). However, there is
      currently no in vivo model detailing the contribution of the renal macrophage to
      the kidney disease associated with HUS. Therefore, renal macrophage recruitment
      and inhibition of infiltrating renal macrophages were evaluated in an established
      HUS mouse model. Macrophage recruitment to the kidney was evident by
      immunohistochemistry 2 h after administration of purified Stx2 and peaked at 48 h
      postinjection. Mice administered a combination of Stx2 and lipopolysaccharide
      (LPS) showed increased macrophage recruitment to the kidney compared to mice
      treated with Stx2 or LPS alone. Monocyte chemoattractants were induced in the
      kidney, including monocyte chemoattractant protein 1 (MCP-1/CCL2), macrophage
      inflammatory protein 1alpha (MIP-1alpha/CCL3), and RANTES (CCL5), in a pattern
      that was coincident with macrophage infiltration as indicated by
      immunohistochemistry, protein, and RNA analyses. MCP-1 was the most abundant
      chemokine, MIP-1alpha was the least abundant, and RANTES levels were
      intermediate. Mice treated with MCP-1, MIP-1alpha, and RANTES neutralizing
      antibodies had a significant decrease in Stx2 plus LPS-induced macrophage
      accumulation in the kidney, indicating that these chemokines are required for
      macrophage recruitment. Furthermore, mice exposed to these three neutralizing
      antibodies had decreased fibrin deposition in their kidneys, implying that
      macrophages contribute to the renal damage associated with HUS.

PMID- 17220321
TI  - Leishmania donovani-induced ceramide as the key mediator of Akt dephosphorylation
      in murine macrophages: role of protein kinase Czeta and phosphatase.
AB  - Leishmania donovani is an intracellular protozoan parasite that impairs the host
      macrophage immune response to render it suitable for its survival and
      establishment. L. donovani-induced immunosuppression and alteration of host cell
      signaling is mediated by ceramide, a pleiotropic second messenger playing an
      important role in regulation of several kinases, including mitogen-activated
      protein kinase and phosphatases. We observed that the endogenous ceramide
      generated during leishmanial infection led to the dephosphorylation of protein
      kinase B (PKB) (Akt) in infected cells. The study of ceramide-mediated Akt
      phosphorylation revealed that Akt was dephosphorylated at both Thr308 and Ser473
      sites in infected cells. Further investigation demonstrated that ceramide was
      also responsible for the induction of PKCzeta, an atypical Ca-independent stress
      kinase, as well as the ceramide-activated protein phosphatases (e.g., protein
      phosphatase 2A [PP2A]). We found that Akt dephosphorylation was mediated by
      ceramide-induced PKCzeta-Akt association and PP2A activation. In addition,
      treatment of L. donovani-infected macrophages with PKCzeta-specific inhibitor
      peptide could restore the translocation of phosphorylated Akt to the cell
      membrane. This study also revealed that ceramide is involved in the inhibition of
      proinflammatory cytokine tumor necrosis factor alpha release by infected
      macrophages. These observations strongly suggest the importance of ceramide in
      the alteration of normal cellular functions, impairment of the kinase/phosphatase
      balance, and thereby establishment of leishmaniasis in the hostile macrophage
      environment.

PMID- 17220324
TI  - A first-degree relative with colorectal cancer: what are we missing?

PMID- 17220322
TI  - Genome-wide analysis of cellular response to bacterial genotoxin CdtB in yeast.
AB  - The cytolethal distending toxins (CDTs) are secreted virulence proteins produced
      by several bacterial pathogens, and the subunit CdtB has the ability to create
      DNA lesions, primarily DNA single-strand breaks (SSBs) in vitro, and cause cell
      cycle arrest, cellular distension, and cell death in both mammalian and yeast
      cells. To elucidate the components of the mechanisms underlying the response to
      CdtB-induced DNA lesions, a CdtB expression plasmid was transformed into a series
      of diploid yeast strains harboring deletions in 4,708 nonessential genes. A total
      of 4,706 of these clones were successfully transformed, which we have now
      designated as a systematic transformation array (STA), and were subsequently
      screened. We identified 61 sensitive strains from the STA whose deleted genes can
      be categorized into a number of groups, including DNA metabolism, chromosome
      segregation, vesicular traffic, RNA catabolism, protein translation,
      morphogenesis, and nuclear transport, as well as one unknown open reading frame.
      However, only 28 of these strains were found to be sensitive to HO endonuclease,
      which is known to create a DNA double-strand break (DSB), suggesting that CdtB
      induced DNA lesion is not similar to the direct DSB. Amazingly, CdtB expression
      elicits severe growth defects in haploid yeast cells, but only marginal defects
      in diploid yeast cells. The presence and absence of genes known to be involved in
      DNA repair in these genome-wide data reveal that CdtB-induced DNA damage is
      specifically repaired well in the diploid by homologous recombination but not by
      other repair mechanisms. Our present results provide insights into how CdtB
      pathogenesis is linked to eukaryotic cellular functions.

PMID- 17220323
TI  - Phagocytosis of Borrelia burgdorferi and Treponema pallidum potentiates innate
      immune activation and induces gamma interferon production.
AB  - We examined the interactions of live and lysed spirochetes with innate immune
      cells. THP-1 monocytoid cells were activated to comparable extents by live
      Borrelia burgdorferi and by B. burgdorferi and Treponema pallidum lysates but
      were poorly activated by live T. pallidum. Because THP-1 cells poorly
      internalized live spirochetes, we turned to an ex vivo peripheral blood
      mononuclear cell system that would more closely reflect spirochete-mononuclear
      phagocyte interactions that occur during actual infection. In this system, B.
      burgdorferi induced significantly greater monocyte activation and inflammatory
      cytokine production than did borrelial lysates or T. pallidum, and only B.
      burgdorferi elicited gamma interferon (IFN-gamma) from NK cells. B. burgdorferi
      was phagocytosed avidly by monocytes, while T. pallidum was not, suggesting that
      the enhanced response to live B. burgdorferi was due to phagocytosis of the
      organism. When cytochalasin D was used to block phagocytosis of live B.
      burgdorferi, cytokine production decreased to levels comparable to those induced
      by B. burgdorferi lysates, while the IFN-gamma response was abrogated altogether.
      In the presence of human syphilitic serum, T. pallidum was efficiently
      internalized and initiated responses resembling those observed with live B.
      burgdorferi, including the production of IFN-gamma by NK cells. Depletion of
      monocytes revealed that they were the primary source of inflammatory cytokines,
      while dendritic cells (DCs) directed IFN-gamma production from innate
      lymphocytes. Thus, phagocytosis of live spirochetes initiates cell activation
      programs in monocytes and DCs that differ qualitatively and quantitatively from
      those induced at the cell surface by lipoprotein-enriched lysates. The greater
      stimulatory capacity of B. burgdorferi versus T. pallidum appears to be explained
      by the successful recognition and phagocytosis of B. burgdorferi by host cells
      and the ability of T. pallidum to avoid detection and uptake by virtue of its
      denuded outer membrane rather than by differences in surface lipoprotein
      expression.

PMID- 17220325
TI  - Risk for high-grade cervical intraepithelial neoplasia associated with variants
      of human papillomavirus types 16 and 18.
AB  - BACKGROUND: Although the variant lineages of human papillomavirus (HPV) types 16
      and 18 are well established, their individual associations with high-grade
      cervical intraepithelial neoplasia (CIN) have not been extensively evaluated.
      METHODS: Study subjects were women participating in the Atypical Squamous Cells
      of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage
      Study who were positive for HPV16 or HPV18 at enrollment. These women were
      followed every 6 months for 2 years. Viral isolates from enrollment samples were
      characterized by DNA sequencing and classified as variant lineages. RESULTS: Over
      a 2-year study period, CIN3 was histologically diagnosed in 291 of the 779 HPV16
      positive women and 47 of the 275 HPV18-positive women. Among women without CIN2-3
      at enrollment, the risk of subsequent CIN3 was 2.7-fold greater for those with
      HPV16 African-2 [95% confidence interval (95% CI), 1.0-7.0] and 3.1-fold greater
      for those with HPV16 Asian American (95% CI, 1.6-6.0), compared with European
      variants. Relative to infection with HPV18 African variants, the risk associating
      subsequent CIN3 was 3.8 (95% CI, 0.9-17.2) for infection with HPV18 European
      variants and 4.8 (95% CI, 1.0-23.6) for infection with HPV18 Asian American
      variants. Similar associations were observed when the 2-year prevalence of CIN3
      was used as the end point. Further, for those with HPV16 European variants, the 2
      year prevalence of CIN3 was higher in White women than in African American women
      (P = 0.01); this trend was reversed for those with HPV16 African-1 variants (P =
      0.22). A similar pattern was present for infections with HPV18 European versus
      African variants. CONCLUSIONS: The lineages of HPV16 and HPV18 variants are
      associated with differing risks for high-grade CIN.

PMID- 17220326
TI  - Viral determinants of human papillomavirus persistence following loop electrical
      excision procedure treatment for cervical intraepithelial neoplasia grade 2 or 3.
AB  - BACKGROUND: Persistent infection with carcinogenic human papillomavirus (HPV)
      causes cervical precancer (cervical intraepithelial neoplasia grade 2+) which, in
      the United States, is commonly treated using the loop electrical excision
      procedure (LEEP). Data from Atypical Squamous Cells of Undetermined Significance
      Low-Grade Squamous Intraepithelial Lesion Triage Study were used to evaluate HPV
      persistence and reappearance after LEEP. METHODS: Cervical specimens, collected
      before LEEP and at 6-month study visits, were tested by L1-PCR for detection of
      >or=27 HPV types. HPV persistence, defined as the same HPV type being present
      before and 6 months after LEEP, was evaluated by: (a) genotype, (b)
      carcinogenicity, and (c) phylogenetic species. HPV infections that cleared post
      LEEP (the complement of persistence) were followed for reappearance of the same
      type. RESULTS: HPV infections (n = 1,130) were detected among 481 women who
      underwent LEEP. Overall, 20.4% [95% confidence interval (95% CI), 18.2-22.9%] of
      infections persisted. Assessment of heterogeneity within the three
      categorizations of HPV showed that phylogenetic species best fit the data.
      Persistence was significantly greater by HPV types in the alpha3 species [all are
      noncarcinogenic; 40.9% (95% CI, 31.8-50.4%)] compared with HPV types in the
      alpha9 (HPV16 and related types) and alpha7 species (HPV18 and related types;
      17.6% and 17.9%, respectively; P < 0.001 for both). HPV reappeared in 7.8% (95%
      CI, 6.1-9.9%) of infections that cleared after LEEP. Infections in the alpha3
      species (22.6%) were the most likely to reappear compared with HPV types in the
      alpha9 (7.5%) and alpha7 (6.8%) species. CONCLUSIONS: Patterns of HPV persistence
      and reappearance following LEEP were better explained by phylogenetic rather than
      standard classifications. HPV types likely to persist after LEEP as well as those
      likely to repopulate the cervical/vaginal epithelium were those in the alpha3
      species, which are in effect not treated, but are not associated with cervical
      cancer and are unlikely to cause disease.

PMID- 17220327
TI  - Type-specific persistence of high-risk human papillomavirus infections in the New
      Independent States of the former Soviet Union Cohort Study.
AB  - BACKGROUND: Prospective follow-up studies have recently suggested that persistent
      high-risk human papillomavirus (HPV) infections play a key role in the
      progression of CIN lesions and in the development of cervical cancer. However,
      data on type-specific persistence, viral integration, and the role of multiple
      infections are scanty. MATERIALS AND METHODS: A cross-sectional/cohort study was
      conducted between 1998 and 2002 in three New Independent States of the former
      Soviet Union comprising a cohort of 3,187 women, of whom 854 women were followed
      up for a mean of 17 months (SD, 11.6). HPV genotyping was done with real-time
      PCR, detecting HPV types 16, 18/45, 31, 33/52/58, 35, and 39. The integration
      status of HPV16 was examined by using a novel Taqman-based PCR method. RESULTS:
      The mean clearance time for the individual high- risk-type infection was 16.5
      months (range = 0.9-34.9 months). HPV16 and HPV31 were the most persistent
      infections (clearance times = 18.1 and 16.2 months, respectively), whereas HPV39
      infections cleared most rapidly. The mean copies per cell in HPV18/45, HPV31,
      HPV33/52/58, and HPV39 infections were higher in persisting HPV infections than
      in HPV infections that cleared, but the difference was not significant.
      Integration of HPV16 was not found to correlate with HPV persistence.
      CONCLUSIONS: A large proportion of women remained high-risk HPV positive after 18
      months. Coinfection with multiple HPV types, viral load, or integration status
      did not correlate with persistence of high-risk HPV infections.

PMID- 17220328
TI  - Endogenous androgens and risk of epithelial ovarian cancer: results from the
      European Prospective Investigation into Cancer and Nutrition (EPIC).
AB  - Few epidemiologic studies have examined the hypothesis that circulating androgens
      are involved in the development of ovarian cancer. We investigated the
      association between prediagnostic serum levels of androgens and sex hormone
      binding globulin (SHBG) and ovarian cancer risk in a case-control study nested
      within the European Prospective Investigation into Cancer and Nutrition cohort.
      One hundred and ninety-two ovarian cancer cases and 346 matched controls not
      using exogenous hormones at baseline blood donation were eligible for the study.
      Serum levels of testosterone, androstenedione, dehydroepiandrosterone sulfate,
      and SHBG were measured by direct immunoassays. Free testosterone (fT) was
      calculated according to mass action laws. Multivariate conditional logistic
      regression was used to estimate odds ratios adjusted for possible confounders.
      Overall, there was no association between serum concentrations of androgens or
      SHBG and ovarian cancer risk. In postmenopausal women, fT concentrations were
      inversely related to risk [highest versus lowest tertile odds ratio 0.45 (0.24
      0.86); P(trend) = 0.01]. Among women diagnosed before the age of 55 years, there
      was a negative association with SHBG and a positive association with fT and
      ovarian cancer risk, although these associations were not statistically
      significant. The present study suggests that circulating androgens and SHBG
      levels are not strongly associated with ovarian cancer risk, although levels of
      fT may be associated with an increased risk among women diagnosed at relatively
      young age. The heterogeneity of results on the associations of fT with ovarian
      cancer risk in postmenopausal women deserves further investigation.

PMID- 17220329
TI  - Incessant ovulation, mucin 1 immunity, and risk for ovarian cancer.
AB  - BACKGROUND: Risk for ovarian cancer correlates directly with "ovulatory years or
      cycles" estimated from time not pregnant, breast-feeding, or using oral
      contraceptives. Recently, we reported that several factors known to reduce
      ovarian cancer risk may operate by inducing antibodies against mucin 1 (MUC1), a
      glycoprotein overexpressed in ovarian cancer. Conversely, other events might
      increase risk by interfering with the development of protective immunity. In this
      study, we examined whether the total number of ovulatory cycles decreases the
      likelihood of anti-MUC1 antibodies and provides an immune basis for the
      association between "incessant ovulation" and ovarian cancer risk. METHODS: From
      1998 to 2003, we enrolled 668 epithelial ovarian cancer cases and 721 controls
      residing in eastern Massachusetts or New Hampshire, collected information on
      menstrual and reproductive events, and obtained blood samples from controls to
      measure anti-MUC1 antibodies. Using logistic regression, we calculated odds
      ratios to evaluate the influence of reproductive factors, including the estimated
      lifetime number of ovulatory cycles on ovarian cancer risk and on the presence of
      MUC1 antibodies in controls. RESULTS: Overall, we observed that early age at
      first birth, cycle lengths >or=30 days, and oral contraceptive use increased the
      likelihood of having anti-MUC1 antibodies. Estimated ovulatory cycles were
      correlated positively with ovarian cancer risk and inversely with the presence of
      anti-MUC1 antibodies among controls ages 46 to 60 years. CONCLUSIONS: These data
      suggest that suppression of MUC1-specific immunity should be considered as an
      additional explanation for the observation that ovarian cancer risk increases
      with the lifetime number of ovulatory cycles.

PMID- 17220330
TI  - Mammographic breast density as a general marker of breast cancer risk.
AB  - Mammographic breast density is a strong risk factor for breast cancer but whether
      breast density is a general marker of susceptibility or is specific to the
      location of the eventual cancer is unknown. A study of 372 incident breast cancer
      cases and 713 matched controls was conducted within the Mayo Clinic mammography
      screening practice. Mammograms on average 7 years before breast cancer were
      digitized, and quantitative measures of percentage density and dense area from
      each side and view were estimated. A regional density estimate accounting for
      overall percentage density was calculated from both mammogram views. Location of
      breast cancer and potential confounders were abstracted from medical records.
      Conditional logistic regression was used to estimate associations, and C
      statistics were used to evaluate the strength of risk prediction. There were
      increasing trends in breast cancer risk with increasing quartiles of percentage
      density and dense area, irrespective of the side of the breast with cancer
      (P(trends) < 0.001). Percentage density from the ipsilateral side [craniocaudal
      (CC): odds ratios (ORs), 1.0 (ref), 1.7, 3.1, and 3.1; mediolateral oblique
      (MLO): ORs, 1.0 (ref), 1.5, 2.2, and 2.8] and the contralateral side [CC: ORs,
      1.0 (ref), 1.8, 2.2, and 3.7; MLO: ORs, 1.0 (ref), 1.6, 1.9, and 2.5] similarly
      predicted case-control status (C-statistics, 0.64-65). Accounting for overall
      percentage density, density in the region where the cancer subsequently developed
      was not a significant risk factor [CC: 1.0 (ref), 1.3, 1.0, and 1.2; MLO: 1.0
      (ref), 1.1, 1.0, and 1.1 for increasing quartiles]. Results did not change when
      examining mammograms 3 years on average before the cancer. Overall mammographic
      density seems to represent a general marker of breast cancer risk that is not
      specific to breast side or location of the eventual cancer.

PMID- 17220332
TI  - Insulin-like growth factor and mammographic density in postmenopausal Norwegian
      women.
AB  - Insulin-like growth factor-I (IGF-I) is associated with breast cancer risk among
      premenopausal women but rarely among postmenopausal women. Recent data from two
      European studies suggested an increased risk of breast cancer with increasing
      levels of IGF-I among women >50 years old or among postmenopausal hormone therapy
      users >or=55 years old. Mammographic density is one of the strongest risk
      factors, and possibly an intermediate marker, for breast cancer. We examined the
      relationship between IGF and mammographic density among postmenopausal women
      overall and according to hormone therapy use. Altogether, 977 postmenopausal
      participants in the Norwegian governmental mammographic screening program had IGF
      concentrations measured by ELISA. Mammograms were classified according to percent
      and absolute mammographic densities using a previously validated computer
      assisted method. After adjustment for age, number of children, age at menopause,
      body mass index, and hormone therapy use, both plasma IGF-I concentration
      (P(trend) = 0.02) and IGF-I/IGF binding protein 3 ratio (P(trend) = 0.02) were
      positively associated with percent mammographic density. The magnitudes of
      differences in percent mammographic density between women in the lowest and
      highest quartiles of IGF-I concentrations were 1.5% absolute difference and 21%
      relative difference. These associations were similar with absolute mammographic
      density as the outcome variable. When the analyses were stratified according to
      hormone therapy use, the associations between IGF-I and mammographic density were
      significant among noncurrent users (P(trend) = 0.03). In conclusion, we found a
      positive but weak association between plasma IGF-I concentrations and both
      percent and absolute mammographic densities among postmenopausal women. These
      associations were found among noncurrent hormone therapy users but not among
      current users.

PMID- 17220331
TI  - Hypermethylation of the breast cancer-associated gene 1 promoter does not predict
      cytologic atypia or correlate with surrogate end points of breast cancer risk.
AB  - Mutation of the breast cancer-associated gene 1 (BRCA1) plays an important role
      in familial breast cancer. Although hypermethylation of the BRCA1 promoter has
      been observed in sporadic breast cancer, its exact role in breast cancer
      initiation and association with breast cancer risk is unknown. The frequency of
      BRCA1 promoter hypermethylation was tested in (a) 14 primary breast cancer
      biopsies and (b) the initial random periareolar fine-needle aspiration (RPFNA)
      cytologic samples obtained from 61 asymptomatic women who were at increased risk
      for breast cancer. BRCA1 promoter hypermethylation was assessed from nucleotide 
      150 to nucleotide +32 relative to the transcription start site. RPFNA specimens
      were stratified for cytologic atypia using the Masood cytology index. BRCA1
      promoter hypermethylation was observed at similar frequency in nonproliferative
      (normal; Masood <or=10: 18%, 2 of 11), hyperplastic (Masood 11-13: 15%, 6 of 41),
      and atypical cytology (Masood 14-17: 22%, 4 of 18; P = 0.79). BRCA1 promoter
      hypermethylation was not associated with (a) family history of breast or ovarian
      cancer or (b) calculated Gail or BRCAPRO risk score. BRCA1 promoter
      hypermethylation was associated with (a) age (P = 0.028) and (b) the combined
      frequency of promoter hypermethylation of the retinoic acid receptor-beta2 (RARB)
      gene, estrogen receptor-alpha (ESR1) gene, and p16 (INK4A) gene (P = 0.003).
      These observations show that BRCA1 promoter hypermethylation (a) is not
      associated with breast cancer risk as measured by mathematical risk models and
      (b) does not predict mammary atypia in RPFNA cytologic samples obtained from high
      risk women.

PMID- 17220333
TI  - A case-control investigation of immune function gene polymorphisms and risk of
      testicular germ cell tumors.
AB  - There is reason to suspect that testicular germ cell tumor (TGCT) development may
      be influenced by cytokines, secreted proteins that modulate tumor immune
      surveillance activity as well as a variety of processes in the testis. To address
      this hypothesis, we conducted a case-control analysis (508 cases, 608 controls)
      of 32 putatively functional single-nucleotide polymorphisms (SNP) in 16 immune
      function genes among non-Hispanic Caucasian participants in the U.S. Servicemen's
      Testicular Tumor Environmental and Endocrine Determinants Study. The TGFB1 Ex5
      73C>T variant was positively associated with TGCT (CT/TT versus CC: odds ratio,
      1.73; 95% confidence interval, 1.01-2.95; P(trend) = 0.05); additionally,
      haplotypes of the assessed TGFB1 SNPs (-509C>T, 327C>T, Ex1-282C>G, and Ex5
      73C>T) differed in frequency between cases and controls (all TGCT, P 0.07;
      seminoma, P 0.04; nonseminoma, P 0.11). We also observed excess frequencies among
      TGCT cases versus controls of LTA 252G (P(trend) = 0.08) and of the TNF variants 
      1042C (P(trend) = 0.06), -1036T (P(trend) = 0.07), and -238G (P(trend) = 0.09).
      Analyses of haplotypes for LTA-TNF SNPs (LTA -91C>A, LTA 252A>G, TNF -863C>A, TNF
      -857C>T, TNF -308G>A, and -238G>A) were similarly suggestive of an association
      with TGCT (P = 0.06) and nonseminoma (P = 0.04), but not seminoma (P = 0.21).
      Polymorphisms in other genes were found to be associated only with seminoma (IL2)
      or nonseminoma (IFNGR2 and IL10). However, none of the associations remained
      noteworthy after applying the false discovery rate method to control for multiple
      testing. In conclusion, our findings suggest that polymorphisms in TGFB1 and
      LTA/TNF, and possibly other immune function genes, may influence susceptibility
      to TGCT.

PMID- 17220334
TI  - High-order interactions among genetic variants in DNA base excision repair
      pathway genes and smoking in bladder cancer susceptibility.
AB  - Cancer is a common multifactor human disease resulting from complex interactions
      between many genetic and environmental factors. In this study, we used a
      multifaceted analytic approach to explore the relationship between eight single
      nucleotide polymorphisms in base excision repair (BER) pathway genes, smoking,
      and bladder cancer susceptibility in a hospital-based case-control study.
      Overall, we did not find an association between any single BER gene single
      nucleotide polymorphism and bladder cancer risk. However, in stratified analysis,
      the OGG1 S326C variant genotypes in ever smokers (odds ratio, 0.74; 95%
      confidence interval, 0.56-0.99) and ADP-ribosyltransferase (ADPRT) V762A variant
      genotypes in never smokers (odds ratio, 0.58; 95% confidence interval, 0.37-0.91)
      conferred a significantly reduced risk. Using logistic regression, we observed
      that there was a two-way interaction between ADPRT V762A and smoking status. We
      next used classification and regression tree analysis to explore high-order gene
      gene and gene-environment interactions. We found that smoking is the most
      important influential factor for bladder cancer risk. Consistent with the above
      findings, we found that the ADPRT V762A was only significantly involved in
      bladder cancer risk in never smokers and the OGG1 S326C was only significantly
      involved in ever smokers. We also observed gene-gene interactions among OGG1
      S326C, XRCC1 R194W, and MUTYH H335Q in ever smokers. Using multifactor
      dimensionality reduction approach, the four-factor model, including smoking
      status, OGG1 S326C (rs1052133), APEX1 D148E (rs3136820), and ADPRT762
      (rs1136410), had the best ability to predict bladder cancer risk with the highest
      cross-validation consistency (100%) and the lowest prediction error (37.02%; P <
      0.001). These results support the hypothesis that genetic variants in BER genes
      contribute to bladder cancer risk through gene-gene and gene-environmental
      interactions.

PMID- 17220335
TI  - Polymorphisms of catechol-O-methyltransferase in men with renal cell cancer.
AB  - The estrogen metabolite, 4-hydroxy-estrogen, has been shown to play a role in
      malignant transformation of male kidneys. To counteract the effects of this
      catechol-estrogen, the catechol-O-methyltransferase (COMT) enzyme is capable of
      neutralizing the genotoxic effects of this compound. A polymorphic variant of
      COMT has been shown to have a reduced enzyme activity, and thus, we hypothesize
      that single nucleotide polymorphisms of the COMT gene can be a risk factor for
      renal cell cancer (RCC). To determine this hypothesis, a study of a Japanese male
      population was used and the genetic distributions of COMT polymorphisms at codons
      62 (C-->T), 72 (G-->T), and 158 (G-->A) were analyzed in 157 normal healthy
      subjects and 123 sporadic RCC (clear cell type) samples by using a sequence
      specific PCR technique. These experiments show that the variant genotype (P =
      0.025) and allele (P = 0.011) at codon 62 is a risk factor for RCC. The odds
      ratio and 95% confidence interval for cancer were 3.16 and 1.29 to 7.73,
      respectively, for the T/T genotype as compared with wild-type. No associations
      for renal cancer were found at either codons 72 or 158 in this Japanese male
      population. However, codons 62 and 158 were observed to be in linkage
      disequilibrium, and haplotype analysis shows the combined forms of T-A, T-G, and
      C-A to be associated with RCC as compared with C-G (P < 0.001). When evaluating
      the risk of COMT polymorphisms with grade of cancer, no associations were
      observed for any of the genotypes. This study is the first to report COMT
      polymorphism to be associated with RCC. These results are important in
      understanding the role of COMT polymorphisms in the pathogenesis of RCC.

PMID- 17220336
TI  - Flavonoids and the risk of renal cell carcinoma.
AB  - Intake of flavonoids has been inversely related to the risk of various common
      neoplasms, but limited data exist on renal cell carcinoma (RCC). We used data
      from a case-control study conducted between 1994 and 2002 in four Italian areas
      to study the relation between major flavonoid classes and RCC. The study included
      767 cases with incident, histologically confirmed RCC and 1,534 hospital controls
      admitted for acute, nonneoplastic conditions and matched with cases by study
      center, sex, and quinquennia of age. We applied published data on food and
      beverage content of six major classes of flavonoids to dietary information
      collected through a validated food frequency questionnaire. After adjustment for
      major recognized confounding factors and total energy intake, the odds ratios for
      subjects in the highest versus the lowest quintile of intake were 0.80 [95%
      confidence interval (95% CI), 0.58-1.11] for total flavonoids, 0.76 (95% CI, 0.56
      1.03) for isoflavones, 0.94 (95% CI, 0.60-1.47) for anthocyanidins, 0.77 (95% CI,
      0.56-1.06) for flavan-3-ols, 0.90 (95% CI, 0.67-1.21) for flavanones, 0.68 (95%
      CI, 0.50-0.93) for flavones, and 0.69 (95% CI, 0.50-0.95) for flavonols.
      Allowance for vegetable and fruit consumption only partly explained these inverse
      relations. Thus, flavonoids, and particularly flavones and flavonols, may
      account, at least in part, for the favorable role of plant foods on RCC.

PMID- 17220337
TI  - Early detection of head and neck cancer: development of a novel screening tool
      using multiplexed immunobead-based biomarker profiling.
AB  - Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease
      that has been linked to altered immune, inflammatory, and angiogenesis responses.
      A better understanding of these aberrant responses might improve early detection
      and prognosis of SCCHN and provide novel therapeutic targets. Previous studies
      examined the role of multiplexed serum biomarkers in small cohorts or SCCHN sera.
      We hypothesized that an expanded panel comprised of multiple cytokines,
      chemokines, growth factors, and other tumor markers, which individually may show
      some promising correlation with disease status, might provide higher diagnostic
      power if used in combination. Thus, we evaluated a novel multianalyte LabMAP
      profiling technology that allows simultaneous measurement of multiple serum
      biomarkers. Concentrations of 60 cytokines, growth factors, and tumor antigens
      were measured in the sera of 116 SCCHN patients before treatment (active disease
      group), 103 patients who were successfully treated (no evidence of disease
      group), and 117 smoker controls without evidence of cancer. The multimarker panel
      offering the highest diagnostic power was comprised of 25 biomarkers, including
      epidermal growth factor, epidermal growth factor receptor, interleukin (IL)-8,
      tissue plasminogen activator inhibitor-1, alpha-fetoprotein, matrix
      metalloproteinase-2, matrix metalloproteinase-3, IFN-alpha, IFN-gamma, IFN
      inducible protein-10, regulated on activation, normal T-cell expressed and
      secreted (RANTES), macrophage inflammatory protein-1alpha, IL-7, IL-17, IL-1
      receptor-alpha, IL-2 receptor, granulocyte colony-stimulating factor, mesothelin,
      insulin-like growth factor binding protein 1, E-selectin, cytokeratin-19,
      vascular cell adhesion molecule, and cancer antigen-125. Statistical analysis
      using an ADE algorithm resulted in a sensitivity of 84.5%, specificity of 98%,
      and 92% of patients in the active disease group correctly classified from a cross
      validation serum set. The data presented show that simultaneous testing using a
      multiplexed panel of serum biomarkers may present a promising new approach for
      the early detection of head and neck cancer.

PMID- 17220338
TI  - Global DNA methylation level in whole blood as a biomarker in head and neck
      squamous cell carcinoma.
AB  - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is commonly associated
      with tobacco and alcohol exposures, although dietary factors, particularly
      folate, and human papillomavirus, are also risk factors. Epigenetic alterations
      are increasingly implicated in the initiation and progression of cancer. Genome
      wide (global) hypomethylation seems to occur in early neoplasia and is a feature
      of genomic DNA derived from solid tumor tissues, including HNSCC. This study
      aimed to determine whether global methylation in DNA derived from whole blood, a
      proxy tissue, is associated with HNSCC and to assess potential modification of
      this property by environmental or behavioral risk factors. METHODS: Global DNA
      methylation levels were assessed using a modified version of the combined
      bisulfite restriction analysis of the LRE1 sequence in a population-based case
      control study of HNSCC from the Boston area. RESULTS: Hypomethylation lead to a
      significant 1.6-fold increased risk for disease (95% confidence interval, 1.1
      2.4), in models controlled for other HNSCC risk factors. Smoking showed a
      significant differential effect (P < 0.03) on blood relative methylation between
      cases and controls. Furthermore, in cases, variant genotype in the MTHFR gene and
      low folate intake showed relationships with decreased global methylation, whereas
      in controls, antibody response to human papillomavirus 16 was associated with an
      increased global methylation level. DISCUSSION: DNA hypomethylation in nontarget
      tissue was independently associated with HNSCC and had a complex relationship
      with the known risk factors associated with the genesis of HNSCC.

PMID- 17220339
TI  - Genetic polymorphisms in folate metabolism and the risk of stomach cancer.
AB  - Folate deficiency has been implicated in the etiology of stomach cancer through
      abnormal DNA methylation and disrupted DNA synthesis and repair. Enzyme-coding
      genes involved in folate metabolism are often polymorphic. In a population-based
      study of 305 cases and 427 controls in Warsaw, Poland, we evaluated the risk of
      stomach cancer in relation to polymorphisms in folate-metabolizing genes,
      including MTHFR (Ex5+79C>T and Ex8-62A>C), MTR (Ex26-20A>G), and MTRR (Ex2-64A>G,
      Ex5+123C>T, Ex15+572C>T, Ex15-405A>T, Ex9-85C>T, Ex15-526G>A, and Ex14+14C>T).
      Polymorphisms in the MTHFR gene were not associated with stomach cancer risk. No
      notable effect was found for polymorphisms in MTR or MTRR either, although MTR
      Ex26-20 A>G and MTRR Ex5+123C>T polymorphisms were associated with a borderline
      increased risk of stomach cancer (MTR Ex26-20A>G, AG/GG versus AA: odds ratio,
      1.35; 95% confidence interval, 0.96-1.90; MTRR Ex5+123C>T, CT/TT versus CC: odds
      ratio, 1.30; 95% confidence interval, 0.93-1.82). We did not find significant
      interactions between polymorphisms in MTHFR, MTR, and MTRR genes and dietary
      folate and alcohol consumption. Our study did not identify strong genetic
      determinants in the folate metabolism pathway for stomach cancer risk.

PMID- 17220340
TI  - Common melanocytic nevi in 7-year-old schoolchildren residing at different
      latitudes in Sweden.
AB  - BACKGROUND: Current epidemiologic research shows consistently that increased
      number of acquired common melanocytic nevi (CMN) is an important risk factor for
      cutaneous malignant melanoma. The purpose of this study was to investigate the
      number of CMN in relation to tanning habits and complexion among 7-year-old
      children residing at different latitudes in Sweden. METHODS: Two municipalities
      were chosen at latitude 65 degrees N to 68 degrees N in the north of Sweden and
      two at latitude 57 degrees N in the south. Children born in 1994 and registered
      in the municipalities were to be included (N = 1,676). A questionnaire was sent
      to their parents asking about the child's tanning habits. A body examination of
      CMN of size >or=2 mm was done by the same trained nurse in 1,380 (82.3%) of the
      children. RESULTS: CMN was significantly less prevalent among children living in
      the north with a prevalence of 5.6 [95% confidence interval (95% CI), 4.8-6.5]
      inland and 6.2 (95% CI, 5.3-7.2) coastal compared with the south with a
      prevalence of 9.5 (95% CI, 8.2-11.0) inland and 10.4 (95% CI, 8.9-12.0) coastal.
      In addition, blond hair, blue/gray/green eyes, holidays at seaside resorts
      abroad, more frequent sunburns, and parents fancying tanning were significant
      predictors of higher prevalence of CMN. CONCLUSIONS: These findings support
      previous evidence that the development of CMN is related to the level of sun
      exposure in childhood expressed as latitude of residence, holidays at seaside
      resort abroad, and number of sunburns. To reduce the incidence of cutaneous
      malignant melanoma, a change in attitude and behavior must start with young
      children and their parents.

PMID- 17220341
TI  - Birth characteristics, maternal reproductive history, and the risk of infant
      leukemia: a report from the Children's Oncology Group.
AB  - Leukemias with MLL gene rearrangements predominate in infants (<1 year of age),
      but not in older children, and may have a distinct etiology. High birth weight,
      higher birth order, and prior fetal loss have, with varying consistency, been
      associated with infant leukemia, but no studies have reported results with
      respect to MLL status. Here, we report for the first time such an analysis.
      During 1999 to 2003, mothers of 240 incident cases (113 MLL(+), 80 MLL(-), and 47
      indeterminate) and 255 random digit dialed controls completed a telephone
      interview. Odds ratios and 95% confidence intervals for quartile of birth weight,
      birth order, gestational age, maternal age at delivery, prior fetal loss, pre
      pregnancy body mass index, and weight gain during pregnancy were obtained using
      unconditional logistic regression; P for linear trend was obtained by modeling
      continuous variables. There was a borderline significant linear trend of
      increasing birth weight with MLL(+) (P = 0.06), but not MLL(-) (P = 0.93), infant
      leukemia. Increasing birth order showed a significant inverse linear trend,
      independent of birth weight, with MLL(+) (P = 0.01), but not MLL(-) (P = 0.18),
      infant leukemia. Other variables of interest were not notably associated with
      infant leukemia regardless of MLL status. This investigation further supports the
      contention that molecularly defined subtypes of infant leukemia have separate
      etiologies.

PMID- 17220342
TI  - Familial effects of BRCA1 genetic mutation testing: changes in perceived family
      functioning.
AB  - This study expands recent research that examines how the receipt of BRCA1 genetic
      test results affects family adaptability and cohesion 1 year after genetic risk
      notification. Study participants were members of a large Utah-based kindred with
      an identified mutation at the BRCA1 locus. The final sample, 90 men and 132
      women, contributed information before genetic testing (baseline) and 4 months
      and/or 1 year after receipt of genetic test results. After controlling for other
      factors such as family coping resources (Family Crises-Oriented Personal
      Evaluation Scale) and strains (Family Strains Index) and the tested individual's
      anxiety levels before genetic testing (state anxiety subscale), men and women
      reported significant declines in family cohesion 1 year after genetic risk
      notification (P < 0.01). There is suggestive evidence that carrier men reported
      increasing adaptability 1 year after risk notification (+0.21 points per month; P
      < 0.10). Having a carrier sister had a positive influence on women's perceived
      family cohesion and adaptability levels, whereas a personal history of cancer,
      having a great deal of caregiving involvement for a female relative with cancer,
      anxiety, and some types of coping resources had a negative effect on men's
      perceived family cohesion and adaptability levels. Although results showed that
      tested parents are perceiving a decline in family functioning after genetic risk
      notification, there is no evidence to suggest that the decline is due to carrier
      status. In fact, it is other life circumstances that exist at the time of the
      genetic testing process that seem to influence the degree to which families
      adjust to the experience and test results.

PMID- 17220343
TI  - Genetic admixture among Hispanics and candidate gene polymorphisms: potential for
      confounding in a breast cancer study?
AB  - Hispanics in the U.S. Southwest have genetic ancestry from Europeans and from
      American Indians, two groups with markedly different breast cancer incidence
      rates. Genetic admixture may therefore bias estimates of associations between
      candidate cancer susceptibility genes and breast cancer in Hispanics. We
      estimated genetic admixture using 15 ancestry-informative markers for 1,239
      Hispanics and 2,505 non-Hispanic Whites in a breast cancer case-control study in
      the Southwest, the Four Corners Study. Confounding risk ratios (CRR) were
      calculated to quantify potential bias due to admixture. Genetic admixture was
      strongly related to self-reported race and ethnic background (P < 0.0001). Among
      Hispanic controls, admixture was significantly associated with allele frequency
      for 5 of 11 candidate gene single nucleotide polymorphisms (SNP) examined.
      Hispanics in the highest versus the lowest quintile of American Indian admixture
      had higher mean body mass index at age 30 years (25.4 versus 23.6 kg/m(2); P =
      0.003), shorter mean height (1.56 versus 1.58 m; P = 0.01), higher prevalence of
      diabetes (14.8% versus 7.2%; P = 0.04), and a larger proportion with less than a
      high school education (38.5% versus 23.2%; P = 0.001). Admixture was not
      associated with breast cancer risk among Hispanics (P = 0.65). CRRs for potential
      bias to candidate SNP-breast cancer risk ratios ranged from 0.99 to 1.01. Thus,
      although genetic admixture in Hispanics was associated with exposures,
      confounding by admixture was negligible due to the null association between
      admixture and breast cancer. CRRs from simulated scenarios indicated that
      appreciable confounding by admixture would occur only when within-group candidate
      SNP allele frequency differences are much larger than any that we observed.

PMID- 17220344
TI  - Detection of aminophenylnorharman, a possible endogenous mutagenic and
      carcinogenic compound, in human urine samples.
AB  - Mutagenic/carcinogenic 9-(4'-aminophenyl)-9H-pyrido[3,4-b]indole
      [aminophenylnorharman (APNH)] is formed from norharman and aniline in the
      presence of cytochrome P450 3A4/1A2. Because both precursors are widely
      distributed in the environment, human exposure is unavoidable. To clarify APNH
      formation in the human body, amounts of the compound in 24-h human urine
      collected from smokers and nonsmokers, eating a normal diet, were analyzed by
      liquid chromatography/electrospray ionization tandem mass spectrometry. In
      addition, norharman and aniline were also analyzed by high-performance liquid
      chromatography and gas chromatography, respectively. APNH could be detected in
      all urine samples at levels 49 to 449 pg for smokers and 21 to 594 pg for
      nonsmokers per 24-h urine, respectively. The amounts of norharman and aniline
      were 46 to 185 ng and 0.70 to 8.10 microg for smokers and 52 to 447 ng and 0.49
      to 5.72 microg for nonsmokers, respectively, per 24-h urine (none of the levels
      differing significantly between smokers and nonsmokers). To exclude exogenous
      exposure to norharman and aniline, we analyzed the levels of APNH, norharman, and
      aniline in urine samples collected from inpatients receiving parenteral
      alimentation. Similar to the healthy volunteers, all urine samples contained 12
      to 338 pg of APNH, 6 to 75 ng of norharman, and 0.33 to 1.86 microg of aniline
      per 24-h urine. These results suggest that APNH should be considered as a novel
      endogenous mutagen/carcinogen; thus, it is very important to determine the
      biological significance of this carcinogen for human cancer development.

PMID- 17220345
TI  - Effect of the Women's Health Initiative study publication on hormone replacement
      therapy use among women who have undergone BRCA1/2 testing.
AB  - BACKGROUND: Since the publication, in July 2002, of the Women's Health Initiative
      (WHI) study, use of hormone replacement therapy (HRT) has decreased substantially
      in the general population. However, little is known about the effect of WHI study
      results on HRT use among women at high risk of breast cancer. The purpose of this
      study is to compare HRT use, prepublication versus postpublication of the WHI
      study, among women tested for BRCA1/2 mutations. METHODS: Participants were >35
      years of age and had received their result of genetic testing (delivered within
      the interdisciplinary research program Interdisciplinary Health Research
      International Team on Breast Cancer Susceptibility), no later than February 28,
      2005. HRT use was reported in self-administered questionnaires, 1 year after
      result disclosure. Women returning their questionnaire before July 17, 2002 were
      classified as pre-WHI, whereas those returning it after October 15, 2002
      comprised the post-WHI group. RESULTS: Four hundred fifty-seven women (199 and
      258 in the pre-WIH and post-WHI groups, respectively) were included in this
      analysis. Globally, there was no difference in HRT use between prepublication and
      postpublication of the WHI study (8% and 11%, respectively; prevalence ratio,
      0.74; 95% confidence interval, 0.43-1.28). However, noncarriers of the familial
      mutation were less likely to use HRT after publication of the WHI study results
      (9%) than before (21%; P = 0.03). CONCLUSIONS: Overall, HRT use among women
      tested for BRCA1/2 mutations is relatively low and apparently uninfluenced by the
      WHI study findings. However, the HRT use reduction among noncarriers is similar
      to that of women in the general population and consistent with the Canadian
      Cancer Society's recent HRT use recommendations.

PMID- 17220346
TI  - Circulating insulin and c-peptide levels and risk of breast cancer among
      predominately premenopausal women.
AB  - Insulin and insulin resistance have been hypothesized to increase the risk of
      breast cancer as insulin increases breast cell proliferation and inhibits sex
      hormone binding globulin. Although insulin is directly related to body weight,
      adiposity is inversely associated with breast cancer risk in premenopausal women
      but directly related to risk in postmenopausal women. To explore the association
      between insulin and c-peptide levels and breast cancer risk, we conducted a
      nested case-control study of predominantly premenopausal women within the Nurses'
      Health Study II cohort. From 1996 to 1999, blood samples were collected from
      29,611 participants. A total of 317 cases were diagnosed after blood collection
      and before June 2003 and matched to 634 controls; 75% of these women were
      premenopausal at blood collection. Logistic regression models, controlling for
      breast cancer risk factors, were used to calculate relative risks (RR) and 95%
      confidence intervals (95% CI). Among women with fasting blood samples (n = 211
      cases), insulin was suggestively inversely associated with breast cancer risk
      (highest versus lowest quartile: RR, 0.5; 95% CI, 0.3-1.0; P(trend) = 0.06).
      Among all women, c-peptide was not associated with breast cancer risk (highest
      versus lowest quartile: RR, 1.1; 95% CI, 0.7-1.7; P(trend) = 0.79); results were
      similar among fasting samples. These associations did not differ by age, body
      mass index, or waist-to-hip ratio. Overall, higher levels of insulin and c
      peptide were not associated with a higher risk of breast cancer among
      predominantly premenopausal women.

PMID- 17220347
TI  - Variant in sex hormone-binding globulin gene and the risk of prostate cancer.
AB  - Sex hormones have been implicated in prostate carcinogenesis and are thought to
      modulate cell proliferation and growth. To investigate the association between
      polymorphisms in hormone-related genes and prostate cancer risk, we conducted a
      two-stage, case-control study within the screening arm of the Prostate, Lung,
      Colorectal, and Ovarian Cancer Screening Trial. Using DNA extracted from blood
      specimens, we initially genotyped 14 single nucleotide polymorphisms in genes
      involved in hormone regulation or metabolism (AKR1C3, CYP1A1, CYP1B1, CYP3A4,
      ESR1, GNRH1, HSD173B, HSD3B2, SHBG, and SRD5A2) in 488 prostate cancer cases and
      617 matched controls. Heterozygotes at SHBG D356N were found to be associated
      with an increased risk of prostate cancer compared with the homozygous wild type,
      particularly among non-Hispanic whites (odds ratio, 1.54; 95% confidence
      interval, 1.13-2.09; P = 0.006). No significant associations were observed with
      the other polymorphisms. The SHBG D356N polymorphism, which has potential
      functional significance, was subsequently genotyped in additional 769 cases and
      1,168 controls. Overall, SHBG D356N heterozygotes were found to have an increased
      risk of prostate cancer among whites (odds ratio, 1.34; 95% confidence interval,
      1.10-1.63; P = 0.0007). This study suggests that genetic variation in SHBG may
      influence prostate cancer susceptibility.

PMID- 17220348
TI  - Haplotype-based analysis of common variation in the growth hormone receptor gene
      and prostate cancer risk.
AB  - The growth hormone receptor (GHR) is potentially involved in prostate cancer
      through its role in stimulating insulin-like growth factor I production and its
      cellular effects on prostate epithelium. We have used a haplotype-based tagging
      approach within CAncer Prostate Sweden, a large retrospective case-control study
      of 2,863 cases and 1,737 controls to investigate if genetic variation in the GHR
      gene influences prostate cancer risk. One haplotype in the 3' region of the GHR
      gene was found associated with prostate cancer risk in elderly men (>65 years old
      at the time of diagnosis), with heterozygote haplotype carriers having an odds
      ratio of 1.65 (95% confidence interval, 1.21-2.16; P = 0.0009, P(corrected) =
      0.03). GHR function has been implicated in the determination of body mass index.
      Interestingly, the same haplotype associated with risk in the 3' end of the GHR
      gene was also associated with a decrease in body mass index in controls (P =
      0.003, P(corrected) = 0.05), possibly indicating some functionality with this
      haplotype. These results suggest that whereas genetic variation in the GHR gene
      does not seem to play a major role in prostate cancer etiology, one haplotype in
      the 3' region may be potentially relevant to cases with later onset of prostate
      cancer.

PMID- 17220349
TI  - Papillary thyroid cancer and polymorphic variants in TSHR- and RET-related genes:
      a nested case-control study within a cohort of U.S. radiologic technologists.
AB  - Several variants in the TSHR and RET signaling pathways genes have been reported
      to be related to cancer risk. We hypothesized that polymorphic variants in these
      genes are associated with the risk of papillary thyroid cancer. A nested case
      control study was conducted within the U.S. Radiologic Technologists cohort.
      Eligible validated papillary thyroid cancer cases (n = 167) and frequency-matched
      (by sex and birth year) controls (n = 491) donated blood for analysis. There were
      no statistically significant associations between papillary thyroid cancer and 10
      selected polymorphic variants in analyses of men and women combined. A borderline
      significant increasing risk was found for RET G691S (P(trend) = 0.05) and was
      especially pronounced among young women. For women under 38 years (the median age
      at diagnosis), the odds ratios were 2.1 (95% confidence interval, 1.2-3.7) for
      those heterozygous for the RET G691S polymorphism and 3.7 (95% confidence
      interval, 1.1-11.8) for those who were homozygous (P(trend) = 0.001). Our data
      provide limited evidence that TSHR- and RET-related genes are related to
      papillary thyroid cancer risk.

PMID- 17220350
TI  - Role of GSTM3 polymorphism in the risk of developing esophageal cancer.
AB  - GSTM3 is involved in detoxification of carcinogens and may be important in
      modulating cancer susceptibility. GSTM3 genotype frequencies were determined in
      peripheral blood DNA of 149 esophageal cancer patients and 200 nonmalignant
      controls using the PCR followed by PAGE. Patients who were heterozygous carriers
      of GSTM3 AB genotype had an enhanced risk for developing esophageal cancer [odds
      ratio (OR), 2.1; 95% confidence interval (95% CI), 1.1-3.7; P = 0.01]. In males,
      the risk due to GSTM3 AB genotype increased further (OR, 3.4; 95% CI, 1.7-6.8; P
      = 0.000). Interaction of GSTM3 AB + BB and GSTM1 null genotypes marginally
      modulated risk (OR, 2.3; 95% CI, 1.1-3.7; P = 0.01). Association with histology
      (adenocarcinoma: OR, 3.4; 95% CI, 1.1-10.9; P = 0.03) and tumor site (middle
      third location: OR, 2.2; 95% CI, 1.1-4.4; P = 0.01; lower third location: OR,
      2.6; 95% CI, 1.2-5.6; P = 0.01) was also documented. Our results suggest that
      GSTM3 polymorphism may influence esophageal cancer susceptibility, in particular
      modulating the risk for adenocarcinoma histology and tumors of the mid and lower
      third region.

PMID- 17220351
TI  - The food frequency questionnaire.

PMID- 17220352
TI  - Vitamin D and Cancer Risk among American Indians.

PMID- 17220353
TI  - The alpha1b-adrenoceptor exists as a higher-order oligomer: effective
      oligomerization is required for receptor maturation, surface delivery, and
      function.
AB  - Approaches to identify G protein-coupled receptor oligomers rather than dimers
      have been lacking. Using concatamers of fluorescent proteins, we established
      conditions to monitor sequential three-color fluorescence resonance energy
      transfer (3-FRET) and used these to detect oligomeric complexes of the alpha(1b)
      adrenoceptor in single living cells. Mutation of putative key hydrophobic
      residues in transmembrane domains I and IV resulted in substantial reduction of
      sequential 3-FRET and was associated with lack of protein maturation, prevention
      of plasma membrane delivery, and elimination of signaling function. Although
      these mutations prevented cell surface delivery, bimolecular fluorescence
      complementation studies indicated that they did not ablate protein-protein
      interactions and confirmed endoplasmic reticulum/Golgi retention of the
      transmembrane domain I plus transmembrane domain IV mutated receptor. The
      transmembrane domain I plus transmembrane domain IV mutated receptor was a
      "dominant-negative" in blocking cell surface delivery of the wild-type receptor.
      Mutations only in transmembrane domain I did not result in a reduction in 3-FRET,
      whereas restricting mutation to transmembrane domain IV did result in reduced 3
      FRET. Mutations in either transmembrane domain I or transmembrane domain IV,
      however, were sufficient to eliminate cell surface delivery. Terminal N
      glycosylation is insufficient to determine cell surface delivery because both
      transmembrane domain I and transmembrane domain IV mutants matured as effectively
      as the wild-type receptor. These data indicate that the alpha(1b)-adrenoceptor is
      able to form oligomeric rather than only simple dimeric complexes and that
      disruption of effective oligomerization by introducing mutations into
      transmembrane domain IV has profound consequences for cell surface delivery and
      function.

PMID- 17220354
TI  - RGS4 modulates serotonin signaling in prefrontal cortex and links to serotonin
      dysfunction in a rat model of schizophrenia.
AB  - Regulator of G protein signaling 4 (RGS4) has recently been identified as one of
      the genes linked to the susceptibility of schizophrenia. However, the functional
      roles of RGS4 and how it may be involved in the pathophysiology of schizophrenia
      remain largely unknown. In this study, we investigated the possible impact of
      RGS4 on the function of serotonin and dopamine receptors, two main targets for
      schizophrenia treatment. Activation of serotonin 5-HT(1A) receptors or dopamine
      D(4) receptors down-regulates the function of NMDA receptor (NMDAR) channel, a
      key player controlling cognition and emotion, in pyramidal neurons of prefrontal
      cortex (PFC). Blocking RGS4 function significantly potentiated the 5-HT(1A)
      regulation of NMDAR current; conversely, overexpression of RGS4 attenuated the 5
      HT(1A) effect. In contrast, the D(4) regulation of NMDAR current was not altered
      by RGS4 manipulation. Moreover, the 5-HT(1A) regulation of NMDA receptors was
      significantly enhanced in a subset of PFC pyramidal neurons from rats treated
      with subchronic phencyclidine, an animal model of schizophrenia, which was found
      to be associated with specifically decreased RGS4 expression in these cells.
      Thus, our study has revealed an important coupling of RGS4 to serotonin signaling
      in cortical neurons and provided a molecular and cellular mechanism underlying
      the potential involvement of RGS4 in the pathophysiology of schizophrenia.

PMID- 17220355
TI  - Vitamin E analogs, a novel group of "mitocans," as anticancer agents: the
      importance of being redox-silent.
AB  - The search for a selective and efficient anticancer agent for treating all
      neoplastic disease has yet to deliver a universally suitable compound(s). The
      majority of established anticancer drugs either are nonselective or lose their
      efficacy because of the constant mutational changes of malignant cells. Until
      recently, a largely neglected target for potential anticancer agents was the
      mitochondrion, showing a considerable promise for future clinical applications.
      Vitamin E (VE) analogs, epitomized by alpha-tocopheryl succinate, belong to the
      group of "mitocans" (mitochondrially targeted anticancer drugs). They are
      selective for malignant cells, cause destabilization of their mitochondria, and
      suppress cancer in preclinical models. This review focuses on our current
      understanding of VE analogs in the context of their proapoptotic/anticancer
      efficacy and suggests that their effect on mitochondria may be amplified by
      modulation of alternative pathways operating in parallel. We show here that the
      analogs of VE that cause apoptosis (which translates into their anticancer
      efficacy) generally do not possess antioxidant (redox) activity and are
      prototypical of the mitocan group of anticancer compounds. Therefore, by analogy
      to Oscar Wilde's play The Importance of Being Earnest, we use the motto in the
      title "the importance of being redox-silent" to emphasize an essentially novel
      paradigm for cancer therapy, in which redox-silence is a prerequisite property
      for most of the anticancer activities described in this communication.

PMID- 17220356
TI  - N-terminal residues control proteasomal degradation of RGS2, RGS4, and RGS5 in
      human embryonic kidney 293 cells.
AB  - Regulator of G protein signaling (RGS) proteins modulate G protein-coupled
      receptor (GPCR) signaling. The N termini of some RGS4-family proteins provide
      receptor specificity and also contain an N-end rule determinant that results in
      ubiquitylation and decreased protein expression. The relevance of these
      mechanisms to other RGS proteins is not fully understood. Thus we examined
      function, receptor specificity, and expression of R4 subfamily RGS proteins
      (RGS2, -3, -4, -5, and -8). Although the N terminus plays a key role in protein
      stability in human embryonic kidney (HEK) 293 cells, we were unable to
      demonstrate specificity of RGS2, -3, -4, -5, or -8 for muscarinic receptors
      (M(1), M(3), and M(5)). However, cellular RGS activity (8 = 3 > 2) was strongly
      correlated with expression; RGS4 and -5 had minimal expression and activity.
      Stabilizing mutations of RGS4 and -5 (C2S) enhanced expression and function with
      a greater influence on RGS4 than on RGS5. We were surprised to find that a
      predicted destabilizing mutation in RGS8 (A2C) did not markedly affect expression
      and had no effect on function. In contrast, a destabilizing mutation in RGS2
      (RGS2-Q2L) recently identified as a rare N-terminal genetic variant in a Japanese
      hypertensive cohort (J Hypertens 23:1497-1505, 2005) showed significantly reduced
      expression and inhibition of angiotensin II (AT(1)) receptor-stimulated
      accumulation of inositol phosphates. We were surprised to find that RGS2-Q2R,
      also predicted to be destabilizing, showed nearly normal expression and function.
      Thus, proteasomal regulation of RGS expression in HEK293 cells strongly controls
      RGS function and a novel RGS2 mutation with decreased protein expression could be
      relevant to the pathophysiology of hypertension in humans.

PMID- 17220357
TI  - Glutathione S-transferase interacting with far-red insensitive 219 is involved in
      phytochrome A-mediated signaling in Arabidopsis.
AB  - Far-red (FR) insensitive 219 (FIN219) was previously shown to be involved in
      phytochrome A-mediated FR light signaling. To further understand its function and
      regulatory relation with other light-signaling components, a yeast two-hybrid
      approach was used to isolate FIN219-interacting partners. Here, we demonstrate
      that FIN219-interacting protein 1 (FIP1) interacts with FIN219 in vitro and in
      vivo and is composed of 217 amino acids that belong to the tau class of the large
      glutathione S-transferase gene family. FIP1 was further shown to have glutathione
      S-transferase activity. The gain of function and partial loss of function of FIP1
      resulted in a hyposensitive hypocotyl phenotype under continuous FR (cFR) light
      and a delayed flowering phenotype under long-day conditions, which suggests that
      FIP1 may exist in a complex to function in the regulation of Arabidopsis
      (Arabidopsis thaliana) development. In addition, FIP1 mRNA was down-regulated in
      the suppressor of phytochrome A-105 1 mutant and differentially expressed in
      constitutive photomorphogenic 1-4 (cop1-4) and cop1-5 mutants under cFR.
      Intriguingly, FIP1 expression was up-regulated in the fin219 mutant under all
      light conditions, except cFR. Furthermore, promoter activity assays revealed that
      FIP1 expression was light dependent, mainly associated with vascular tissues, and
      developmentally regulated. Subcellular localization studies revealed that the
      beta-glucuronidase-FIP1 fusion protein was localized in the nucleus and
      cytoplasm. Taken together, these data indicate that FIP1 may interact with FIN219
      to regulate cell elongation and flowering in response to light.

PMID- 17220358
TI  - Pterin and folate salvage. Plants and Escherichia coli lack capacity to reduce
      oxidized pterins.
AB  - Dihydropterins are intermediates of folate synthesis and products of folate
      breakdown that are readily oxidized to their aromatic forms. In trypanosomatid
      parasites, reduction of such oxidized pterins is crucial for pterin and folate
      salvage. We therefore sought evidence for this reaction in plants. Three lines of
      evidence indicated its absence. First, when pterin-6-aldehyde or 6
      hydroxymethylpterin was supplied to Arabidopsis (Arabidopsis thaliana), pea
      (Pisum sativum), or tomato (Lycopersicon esculentum) tissues, no reduction of the
      pterin ring was seen after 15 h, although reduction and oxidation of the side
      chain of pterin-6-aldehyde were readily detected. Second, no label was
      incorporated into folates when 6-[(3)H]hydroxymethylpterin was fed to cultured
      Arabidopsis plantlets for 7 d, whereas [(3)H]folate synthesis from p
      [(3)H]aminobenzoate was extensive. Third, no NAD(P)H-dependent pterin ring
      reduction was found in tissue extracts. Genetic evidence showed a similar
      situation in Escherichia coli: a GTP cyclohydrolase I (folE) mutant, deficient in
      pterin synthesis, was rescued by dihydropterins but not by the corresponding
      oxidized forms. Expression of a trypanosomatid pterin reductase (PTR1) enabled
      rescue of the mutant by oxidized pterins, establishing that E. coli can take up
      oxidized pterins but cannot reduce them. Similarly, a GTP cyclohydrolase I (fol2)
      mutant of yeast (Saccharomyces cerevisiae) was rescued by dihydropterins but not
      by most oxidized pterins, 6-hydroxymethylpterin being an exception. These results
      show that the capacity to reduce oxidized pterins is not ubiquitous in folate
      synthesizing organisms. If it is lacking, folate precursors or breakdown products
      that become oxidized will permanently exit the metabolically active pterin pool.

PMID- 17220359
TI  - Dual lipid modification of Arabidopsis Ggamma-subunits is required for efficient
      plasma membrane targeting.
AB  - Posttranslational lipid modifications are important for proper localization of
      many proteins in eukaryotic cells. However, the functional interrelationships
      between lipid modification processes in plants remain unclear. Here we
      demonstrate that the two heterotrimeric G-protein gamma-subunits from Arabidopsis
      (Arabidopsis thaliana), AGG1 and AGG2, are prenylated, and AGG2 is S-acylated. In
      wild type, enhanced yellow fluorescent protein-fused AGG1 and AGG2 are associated
      with plasma membranes, with AGG1 associated with internal membranes as well. Both
      can be prenylated by either protein geranylgeranyltransferase I (PGGT-I) or
      protein farnesyltransferase (PFT). Their membrane localization is intact in
      mutants lacking PFT activity and largely intact in mutants lacking PGGT-I
      activity but is disrupted in mutants lacking both PFT and PGGT-I activity. Unlike
      in mammals, Arabidopsis Ggammas do not rely on functional Galpha for membrane
      targeting. Mutation of the sixth to last cysteine, the putative S-acylation
      acceptor site, causes a dramatic change in AGG2 but not AGG1 localization
      pattern, suggesting S-acylation serves as an important additional signal for AGG2
      to be targeted to the plasma membrane. Domain-swapping experiments suggest that a
      short charged sequence at the AGG2 C terminus contributes to AGG2's efficient
      membrane targeting compared to AGG1. Our data show the large degree to which PFT
      and PGGT-I can compensate for each other in plants and suggest that differential
      lipid modification plays an important regulatory role in plant protein
      localization.

PMID- 17220360
TI  - The Arabidopsis aleurone layer responds to nitric oxide, gibberellin, and
      abscisic acid and is sufficient and necessary for seed dormancy.
AB  - Seed dormancy is a common phase of the plant life cycle, and several parts of the
      seed can contribute to dormancy. Whole seeds, seeds lacking the testa, embryos,
      and isolated aleurone layers of Arabidopsis (Arabidopsis thaliana) were used in
      experiments designed to identify components of the Arabidopsis seed that
      contribute to seed dormancy and to learn more about how dormancy and germination
      are regulated in this species. The aleurone layer was found to be the primary
      determinant of seed dormancy. Embryos from dormant seeds, however, had a lesser
      growth potential than those from nondormant seeds. Arabidopsis aleurone cells
      were examined by light and electron microscopy, and cell ultrastructure was
      similar to that of cereal aleurone cells. Arabidopsis aleurone cells responded to
      nitric oxide (NO), gibberellin (GA), and abscisic acid, with NO being upstream of
      GA in a signaling pathway that leads to vacuolation of protein storage vacuoles
      and abscisic acid inhibiting vacuolation. Molecular changes that occurred in
      embryos and aleurone layers prior to germination were measured, and these data
      show that both the aleurone layer and the embryo expressed the NO-associated gene
      AtNOS1, but only the embryo expressed genes for the GA biosynthetic enzyme GA3
      oxidase.

PMID- 17220361
TI  - Neural network analyses of infrared spectra for classifying cell wall
      architectures.
AB  - About 10% of plant genomes are devoted to cell wall biogenesis. Our goal is to
      establish methodologies that identify and classify cell wall phenotypes of
      mutants on a genome-wide scale. Toward this goal, we have used a model system,
      the elongating maize (Zea mays) coleoptile system, in which cell wall changes are
      well characterized, to develop a paradigm for classification of a comprehensive
      range of cell wall architectures altered during development, by environmental
      perturbation, or by mutation. Dynamic changes in cell walls of etiolated maize
      coleoptiles, sampled at one-half-d intervals of growth, were analyzed by chemical
      and enzymatic assays and Fourier transform infrared spectroscopy. The primary
      walls of grasses are composed of cellulose microfibrils, glucuronoarabinoxylans,
      and mixed-linkage (1 --> 3),(1 --> 4)-beta-D-glucans, together with smaller
      amounts of glucomannans, xyloglucans, pectins, and a network of polyphenolic
      substances. During coleoptile development, changes in cell wall composition
      included a transient appearance of the (1 --> 3),(1 --> 4)-beta-D-glucans, a
      gradual loss of arabinose from glucuronoarabinoxylans, and an increase in the
      relative proportion of cellulose. Infrared spectra reflected these dynamic
      changes in composition. Although infrared spectra of walls from embryonic,
      elongating, and senescent coleoptiles were broadly discriminated from each other
      by exploratory principal components analysis, neural network algorithms (both
      genetic and Kohonen) could correctly classify infrared spectra from cell walls
      harvested from individuals differing at one-half-d interval of growth. We tested
      the predictive capabilities of the model with a maize inbred line, Wisconsin 22,
      and found it to be accurate in classifying cell walls representing developmental
      stage. The ability of artificial neural networks to classify infrared spectra
      from cell walls provides a means to identify many possible classes of cell wall
      phenotypes. This classification can be broadened to phenotypes resulting from
      mutations in genes encoding proteins for which a function is yet to be described.

PMID- 17220362
TI  - Recent proliferation and translocation of pollen group 1 allergen genes in the
      maize genome.
AB  - The dominant allergenic components of grass pollen are known by immunologists as
      group 1 allergens. These constitute a set of closely related proteins from the
      beta-expansin family and have been shown to have cell wall-loosening activity.
      Group 1 allergens may facilitate the penetration of pollen tubes through the
      grass stigma and style. In maize (Zea mays), group 1 allergens are divided into
      two classes, A and B. We have identified 15 genes encoding group 1 allergens in
      maize, 11 genes in class A and four genes in class B, as well as seven
      pseudogenes. The genes in class A can be divided by sequence relatedness into two
      complexes, whereas the genes in class B constitute a single complex. Most of the
      genes identified are represented in pollen-specific expressed sequence tag
      libraries and are under purifying selection, despite the presence of multiple
      copies that are nearly identical. Group 1 allergen genes are clustered in at
      least six different genomic locations. The single class B location and one of the
      class A locations show synteny with the rice (Oryza sativa) regions where
      orthologous genes are found. Both classes are expressed at high levels in mature
      pollen but at low levels in immature flowers. The set of genes encoding maize
      group 1 allergens is more complex than originally anticipated. If this situation
      is common in grasses, it may account for the large number of protein variants, or
      group 1 isoallergens, identified previously in turf grass pollen by
      immunologists.

PMID- 17220363
TI  - Plant Gene and Alternatively Spliced Variant Annotator. A plant genome annotation
      pipeline for rice gene and alternatively spliced variant identification with
      cross-species expressed sequence tag conservation from seven plant species.
AB  - The completion of the rice (Oryza sativa) genome draft has brought unprecedented
      opportunities for genomic studies of the world's most important food crop.
      Previous rice gene annotations have relied mainly on ab initio methods, which
      usually yield a high rate of false-positive predictions and give only limited
      information regarding alternative splicing in rice genes. Comparative approaches
      based on expressed sequence tags (ESTs) can compensate for the drawbacks of ab
      initio methods because they can simultaneously identify experimental data
      supported genes and alternatively spliced transcripts. Furthermore, cross-species
      EST information can be used to not only offset the insufficiency of same-species
      ESTs but also derive evolutionary implications. In this study, we used ESTs from
      seven plant species, rice, wheat (Triticum aestivum), maize (Zea mays), barley
      (Hordeum vulgare), sorghum (Sorghum bicolor), soybean (Glycine max), and
      Arabidopsis (Arabidopsis thaliana), to annotate the rice genome. We developed a
      plant genome annotation pipeline, Plant Gene and Alternatively Spliced Variant
      Annotator (PGAA). Using this approach, we identified 852 genes (931 isoforms) not
      annotated in other widely used databases (i.e. the Institute for Genomic
      Research, National Center for Biotechnology Information, and Rice Annotation
      Project) and found 87% of them supported by both rice and nonrice EST evidence.
      PGAA also identified more than 44,000 alternatively spliced events, of which
      approximately 20% are not observed in the other three annotations. These novel
      annotations represent rich opportunities for rice genome research, because the
      functions of most of our annotated genes are currently unknown. Also, in the PGAA
      annotation, the isoforms with non-rice-EST-supported exons are significantly
      enriched in transporter activity but significantly underrepresented in
      transcription regulator activity. We have also identified potential lineage
      specific and conserved isoforms, which are important markers in evolutionary
      studies. The data and the Web-based interface, RiceViewer, are available for
      public access at http://RiceViewer.genomics.sinica.edu.tw/.

PMID- 17220364
TI  - DELLAs contribute to plant photomorphogenesis.
AB  - Plant morphogenesis is profoundly influenced by light (a phenomenon known as
      photomorphogenesis). For example, light inhibits seedling hypocotyl growth via
      activation of phytochromes and additional photoreceptors. Subsequently,
      information is transmitted through photoreceptor-linked signal transduction
      pathways and used (via previously unknown mechanisms) to control hypocotyl
      growth. Here we show that light inhibition of Arabidopsis (Arabidopsis thaliana)
      hypocotyl growth is in part dependent on the DELLAs (a family of nuclear growth
      restraining proteins that mediate the effect of the phytohormone gibberellin [GA]
      on growth). We show that light inhibition of growth is reduced in DELLA-deficient
      mutant hypocotyls. We also show that light activation of phytochromes promotes
      the accumulation of DELLAs. A green fluorescent protein (GFP)-tagged DELLA (GFP
      RGA) accumulates in elongating cells of light-grown, but not dark-grown,
      transgenic wild-type hypocotyls. Furthermore, transfer of seedlings from light to
      dark (or vice versa) results in rapid changes in hypocotyl GFP-RGA accumulation,
      changes that are paralleled by rapid alterations in the abundance in hypocotyls
      of transcripts encoding enzymes of GA metabolism. These observations suggest that
      light-dependent changes in hypocotyl GFP-RGA accumulation are a consequence of
      light-dependent changes in bioactive GA level. Finally, we show that GFP
      accumulation and quantitative modulation of hypocotyl growth is proportionate
      with light energy dose (the product of exposure duration and fluence rate).
      Hence, DELLAs inhibit hypocotyl growth during the light phase of the day-night
      cycle via a mechanism that is quantitatively responsive to natural light
      variability. We conclude that DELLAs are a major component of the adaptively
      significant mechanism via which light regulates plant growth during
      photomorphogenesis.

PMID- 17220365
TI  - The coronatine-insensitive 1 mutation reveals the hormonal signaling interaction
      between abscisic acid and methyl jasmonate in Arabidopsis guard cells. Specific
      impairment of ion channel activation and second messenger production.
AB  - Methyl jasmonate (MeJA) elicits stomatal closing similar to abscisic acid (ABA),
      but whether the two compounds use similar or different signaling mechanisms in
      guard cells remains to be clarified. We investigated the effects of MeJA and ABA
      on second messenger production and ion channel activation in guard cells of wild
      type Arabidopsis (Arabidopsis thaliana) and MeJA-insensitive coronatine
      insensitive 1 (coi1) mutants. The coi1 mutation impaired MeJA-induced stomatal
      closing but not ABA-induced stomatal closing. MeJA as well as ABA induced
      production of reactive oxygen species (ROS) and nitric oxide (NO) in wild-type
      guard cells, whereas MeJA did not induce production of ROS and NO in coi1 guard
      cells. The experiments using an inhibitor and scavengers demonstrated that both
      ROS and NO are involved in MeJA-induced stomatal closing as well as ABA-induced
      stomatal closing. Not only ABA but also MeJA activated slow anion channels and
      Ca(2+) permeable cation channels in the plasma membrane of wild-type guard cell
      protoplasts. However, in coi1 guard cell protoplasts, MeJA did not elicit either
      slow anion currents or Ca(2+) permeable cation currents, but ABA activated both
      types of ion channels. Furthermore, to elucidate signaling interaction between
      ABA and MeJA in guard cells, we examined MeJA signaling in ABA-insensitive mutant
      ABA-insensitive 2 (abi2-1), whose ABA signal transduction cascade has some
      disruption downstream of ROS production and NO production. MeJA also did not
      induce stomatal closing but stimulated production of ROS and NO in abi2-1. These
      results suggest that MeJA triggers stomatal closing via a receptor distinct from
      the ABA receptor and that the coi1 mutation disrupts MeJA signaling upstream of
      the blanch point of ABA signaling and MeJA signaling in Arabidopsis guard cells.

PMID- 17220366
TI  - The lipopolysaccharide of Sinorhizobium meliloti suppresses defense-associated
      gene expression in cell cultures of the host plant Medicago truncatula.
AB  - In the establishment of symbiosis between Medicago truncatula and the nitrogen
      fixing bacterium Sinorhizobium meliloti, the lipopolysaccharide (LPS) of the
      microsymbiont plays an important role as a signal molecule. It has been shown in
      cell cultures that the LPS is able to suppress an elicitor-induced oxidative
      burst. To investigate the effect of S. meliloti LPS on defense-associated gene
      expression, a microarray experiment was performed. For evaluation of the M.
      truncatula microarray datasets, the software tool MapMan, which was initially
      developed for the visualization of Arabidopsis (Arabidopsis thaliana) datasets,
      was adapted by assigning Medicago genes to the ontology originally created for
      Arabidopsis. This allowed functional visualization of gene expression of M.
      truncatula suspension-cultured cells treated with invertase as an elicitor. A
      gene expression pattern characteristic of a defense response was observed.
      Concomitant treatment of M. truncatula suspension-cultured cells with invertase
      and S. meliloti LPS leads to a lower level of induction of defense-associated
      genes compared to induction rates in cells treated with invertase alone. This
      suppression of defense-associated transcriptional rearrangement affects genes
      induced as well as repressed by elicitation and acts on transcripts connected to
      virtually all kinds of cellular processes. This indicates that LPS of the
      symbiont not only suppresses fast defense responses as the oxidative burst, but
      also exerts long-term influences, including transcriptional adjustment to
      pathogen attack. These data indicate a role for LPS during infection of the plant
      by its symbiotic partner.

PMID- 17220368
TI  - Acute alcohol intoxication increases interleukin-18-mediated neutrophil
      infiltration and lung inflammation following burn injury in rats.
AB  - In this study, we examined whether IL-18 plays a role in lung inflammation
      following alcohol (EtOH) and burn injury. Male rats ( approximately 250 g) were
      gavaged with EtOH to achieve a blood EtOH level of approximately 100 mg/dl before
      burn or sham injury ( approximately 12.5% total body surface area). Immediately
      after injury, rats were treated with vehicle, caspase-1 inhibitor AC-YVAD-CHO to
      block IL-18 production or with IL-18 neutralizing anti-IL-18 antibodies. In
      another group, rats were treated with anti-neutrophil antiserum approximately 16
      h before injury to deplete neutrophils. On day 1 after injury, lung tissue IL-18,
      neutrophil chemokines (CINC-1/CINC-3), ICAM-1, neutrophil infiltration, MPO
      activity, and water content (i.e., edema) were significantly increased in rats
      receiving a combined insult of EtOH and burn injury compared with rats receiving
      either EtOH intoxication or burn injury alone. Treatment of rats with caspase-1
      inhibitor prevented the increase in lung tissue IL-18, CINC-1, CINC-3, ICAM-1,
      MPO activity, and edema following EtOH and burn injury. The increase in lung IL
      18, MPO, and edema was also prevented in rats treated with anti-IL-18 antibodies.
      Furthermore, administration of anti-neutrophil antiserum also attenuated the
      increase in lung MPO activity and edema, but did not prevent the increase in IL
      18 levels following EtOH and burn injury. These findings suggest that acute EtOH
      intoxication before burn injury upregulates IL-18, which in turn contributes to
      increased neutrophil infiltration. Furthermore, the presence of neutrophils
      appears to be critical for IL-18-meditaed increased lung tissue edema following a
      combined insult of EtOH and burn injury.

PMID- 17220367
TI  - Auxin biosynthesis by the YUCCA genes in rice.
AB  - Although indole-3-acetic acid (IAA), the predominant auxin in plants, plays a
      critical role in various plant growth and developmental processes, its
      biosynthesis and regulation have not been clearly elucidated. To investigate the
      molecular mechanisms of IAA synthesis in rice (Oryza sativa), we identified seven
      YUCCA-like genes (named OsYUCCA1-7) in the rice genome. Plants overexpressing
      OsYUCCA1 exhibited increased IAA levels and characteristic auxin overproduction
      phenotypes, whereas plants expressing antisense OsYUCCA1 cDNA displayed defects
      that are similar to those of rice auxin-insensitive mutants. OsYUCCA1 was
      expressed in almost all of the organs tested, but its expression was restricted
      to discrete areas, including the tips of leaves, roots, and vascular tissues,
      where it overlapped with expression of a beta-glucuronidase reporter gene
      controlled by the auxin-responsive DR5 promoter. These observations are
      consistent with an important role for the rice enzyme OsYUCCA1 in IAA
      biosynthesis via the tryptophan-dependent pathway.

PMID- 17220369
TI  - Regulation of interleukin-8 via an airway epithelial signaling cascade.
AB  - Airways function as an innate immune organ against airborne bacteria that are
      inhaled and deposited in airways. One of the mechanisms of host defense is to
      recruit neutrophils into airways to clear the invaders. Airway epithelial cells
      produce neutrophil chemoattractant interleukin (IL)-8 in response to invading
      bacteria. In this study we show a signaling pathway on the plasma surface of
      human airway epithelial NCI-H292 cells that regulate IL-8 production in response
      to a model inflammatory stimulus, phorbol 12-myristate 13-acetate, and a
      pathophysiological stimulus, gram-negative bacterial lipopolysaccharide. First,
      we show that EGF receptor (EGFR) and MAP kinase ERK1/2 are involved in IL-8
      expression by these stimuli. Second, we show that EGFR ligand transforming growth
      factor (TGF)-alpha mediates IL-8 production. Third, we show that tumor necrosis
      factor-alpha-converting enzyme (TACE) is required for IL-8 production by cleaving
      EGFR proligand proTGF-alpha into soluble TGF-alpha, activating EGFR. Last, we
      show that dual oxidase 1 (Duox1), a homolog of NADPH oxidase in airways, mediates
      TACE activation and IL-8 expression via generation of reactive oxygen species. In
      summary, we describe a signaling pathway, Duox1-TACE-TGF-alpha-EGFR, on the
      surface of airway epithelial (NCI-H292) cells that mediates airway epithelial
      defense against bacterial infection by producing IL-8. This pathway, which also
      regulates mucin production in human airways, provides mechanisms for killing
      foreign organisms and for their clearance.

PMID- 17220370
TI  - The alcoholic lung: epidemiology, pathophysiology, and potential therapies.
AB  - Epidemiological evidence gathered only in the past decade reveals that alcohol
      abuse independently increases the risk of developing the acute respiratory
      distress syndrome by as much as three- to fourfold. Experimental models and
      clinical studies are beginning to elucidate the mechanisms underlying this
      previously unrecognized association and are revealing for the first time that
      chronic alcohol abuse causes discrete changes, particularly within the alveolar
      epithelium, that render the lung susceptible to acute edematous injury in
      response to sepsis, trauma, and other inflammatory insults. Recent studies in
      relevant animal models as well as in human subjects are identifying common
      mechanisms by which alcohol abuse targets both the alveolar epithelium and the
      alveolar macrophage, such that the risks for acute lung injury and pulmonary
      infections are inextricably linked. Specifically, chronic alcohol ingestion
      decreases the levels of the antioxidant glutathione within the alveolar space by
      as much as 80-90%, and, as a consequence, impairs alveolar epithelial surfactant
      production and barrier integrity, decreases alveolar macrophage function, and
      renders the lung susceptible to oxidant-mediated injury. These changes are often
      subclinical and may not manifest as detectable lung impairment until challenged
      by an acute insult such as sepsis or trauma. However, even otherwise healthy
      alcoholics have evidence of severe oxidant stress in the alveolar space that
      correlates with alveolar epithelial and macrophage dysfunction. This review
      focuses on the epidemiology and the pathophysiology of alcohol-induced lung
      dysfunction and discusses potential new treatments suggested by recent
      experimental findings.

PMID- 17220371
TI  - Bleomycin treatment causes enhancement of virus replication in the lungs of SHIV
      infected macaques.
AB  - Pneumonia is a major complication of human immunodeficiency virus (HIV)
      pathogenesis but it develops only after prolonged infection. We used the macaque
      model to explore a hypothesis that the disease is a two-stage process, the first
      stage being establishment of the viral infection in the lung and the second being
      amplification of virus replication by host factors induced by chemical agents or
      opportunistic pathogens in the lung. Bleomycin, a chemical known to induce
      diffuse alveolar damage and pulmonary fibrosis with accumulation of macrophages
      and a rich T helper type 2 (Th2) cytokine environment, was inoculated
      intratracheally into five of eight SHIV 89.6P-infected macaques and into one
      uninfected macaque. Three additional simian HIV (SHIV)-infected macaques without
      bleomycin treatment served as untreated virus controls. Although none of the
      animals became clinically ill, bleomycin induced classical host responses in the
      lungs of all the treated, virus-infected macaques. There was enhanced production
      of the chemokine, monocyte chemotactic protein-1 (MCP-1), that had previously
      been shown to cause enhanced replication of the virus. Four of the five treated
      animals developed more productive SHIV infection in the lungs compared with the
      infected untreated animals. Enhanced virus replication was found primarily in
      infiltrating macrophages. Enhanced replication of the virus in the lungs was
      associated with host factors induced by the drug and supported the hypothesis for
      a two-stage process of pulmonary pathogenesis.

PMID- 17220372
TI  - Human bronchial epithelial cell transcriptome: gene expression changes following
      acute exposure to whole cigarette smoke in vitro.
AB  - Cigarette smoke is a complex mixture of more than 4,000 constituents. Its effects
      on cell biology are poorly understood, partly because whole smoke exposure in
      vitro is technically challenging. To investigate the effects of smoke on cell
      signaling and function, a three-dimensional air-liquid interface model of
      tracheobronchial epithelium, grown from primary human lung epithelial cells, was
      exposed to air or whole mainstream cigarette smoke for 1 h in a purpose-designed
      chamber. Gene expression profiles were then determined at 1, 6, and 24 h
      postexposure using Affymetrix HGU133-2 Plus microarrays. Cells from three
      different donors were used in the study, and the experiment was performed in
      triplicate for each donor. Genes significantly regulated by smoke, compared with
      the air control, in all experiments were determined. Genes exhibiting
      differential expression were assigned to functional categories and mapped to
      signaling pathways. Effects were observed on many cellular processes including
      xenobiotic metabolism, oxidant/antioxidant balance, and DNA damage and repair.
      Notably, there was marked downregulation of the transforming growth factor-beta
      pathway, which has not been previously reported. This study provides important
      data on the acute effects of whole cigarette smoke on mucociliary epithelium and
      may be used to gain a greater understanding of smoke toxicity.

PMID- 17220373
TI  - Protective effect of orally administered carnosine on bleomycin-induced lung
      injury.
AB  - Carnosine is an endogenously synthesized dipeptide composed of beta-alanine and L
      histidine. It acts as a free radical scavenger and possesses antioxidant
      properties. Carnosine reduces proinflammatory and profibrotic cytokines such as
      transforming growth factor-beta (TGF-beta), IL-1, and TNF-alpha in different
      experimental settings. In the present study, we investigated the efficacy of
      carnosine on the animal model of bleomycin-induced lung injury. Mice were
      subjected to intratracheal administration of bleomycin and were assigned to
      receive carnosine daily by an oral bolus of 150 mg/kg. One week after fibrosis
      induction, bronchoalveolar lavage (BAL) cell counts and TGF-beta levels, lung
      histology, and immunohistochemical analyses for myeloperoxidase, TGF-beta,
      inducible nitric oxide synthase, nitrotyrosine, and poly(ADP-ribose) polymerase
      were performed. Finally, apoptosis was quantified by terminal
      deoxynucleotidyltransferase-mediated UTP end-labeling assay. After bleomycin
      administration, carnosine-treated mice exhibited a reduced degree of lung damage
      and inflammation compared with wild-type mice, as shown by the reduction of 1)
      body weight, 2) mortality rate, 3) lung infiltration by neutrophils
      (myeloperoxidase activity and BAL total and differential cell counts), 4) lung
      edema, 5) histological evidence of lung injury and collagen deposition, 6) lung
      myeloperoxidase, TGF-beta, inducible nitric oxide synthase, nitrotyrosine, and
      poly(ADP-ribose) polymerase immunostaining, 7) BAL TGF-beta levels, and 8)
      apoptosis. Our results indicate that orally administered carnosine is able to
      prevent bleomycin-induced lung injury likely through its direct antioxidant
      properties. Carnosine is already available for human use. It might prove useful
      as an add-on therapy for the treatment of fibrotic disorders of the lung where
      oxidative stress plays a role, such as for idiopathic pulmonary fibrosis, a
      disease that still represents a major challenge to medical treatment.

PMID- 17220374
TI  - Extracellular proteasome in the human alveolar space: a new housekeeping enzyme?
AB  - We hypothesized that 20S proteasome is present and functional in the
      extracellular alveolar space in humans. Proteasomal activity was measured in
      bronchoalveolar lavage (BAL) supernatant from eight humans using specific
      proteasomal fluorogenic substrates and I(125)-albumin with and without specific
      proteasome inhibitors. Furthermore, gelfiltration, Western blot technique, and
      mass spectrometry were applied for proteasome characterization. All proteasomal
      fluorogenic substrates were hydrolyzed by BAL supernatant, with hydrolysis
      inhibited by epoxomicin (P = 0.024) and other proteasome inhibitors as well. E64,
      a lysosomal inhibitor, did not inhibit enzyme activity. The majority of
      proteolytic activity was detected in BAL supernatant rather than in the cell
      pellet. No correlation was found between proteasomal hydrolysis in BAL
      supernatant and lactate dehydrogenase activity, the total cell count in the cell
      pellet, and the fraction of avital cells in the cell pellet, ruling out cell
      lysis as a major source of proteasomal activity. Gelfiltration revealed
      hydrolyzing activity in the supernatant at 660 kDa and proteasome core proteins
      after analysis by ESI-QqTOF mass spectrometry. Furthermore, Western blots using a
      polyclonal antibody against proteasomal alpha-/beta-subunits detected proteasomal
      proteins in the typical 20- to 30-kDa range in BAL supernatant. Incubation of BAL
      supernatant with I(125)-albumin showed a high mean cleavage rate (101.8 microg/ml
      x h lavage +/- 46 SD) that was inhibited by epoxomicin (P = 0.013) and was ATP
      and ubiquitin independent. We identified for the first time extracellular,
      biologically active, ATP- and ubiquitin-independent 20S proteasome in the human
      alveolar space, with a high albumin cleavage rate. Possibly, the proteasome
      assists in maintenance of a low intra-alveolar oncotic pressure and/or alveolar
      protein degradation.

PMID- 17220375
TI  - Yin Yang 1 enhances cyclooxygenase-2 gene expression in macrophages.
AB  - Expression of cyclooxygenase-2 (COX-2) is associated with the pathogenesis of
      inflammation and various cancers, including lung cancer. Yin Yang 1 (YY1) is a
      zinc-finger transcription factor that interacts with histone acetyltransferases
      and deacetylases for its transcriptional activity and also is involved in
      inflammation and tumorigenesis. We investigated whether YY1 regulates COX-2
      expression. We located a possible YY1 binding site proximal to the transcription
      initiation site of the COX-2 promoter. Electrophoretic mobility shift assays show
      that YY1 bound to the putative YY1 site in vitro. To show biological relevance,
      we performed chromatin immunoprecipitation assays showing that lipopolysaccharide
      (LPS) treatment induced YY1 binding to the cognate site in the endogenous COX-2
      promoter. Overexpression of YY1 in macrophages treated with either LPS or live
      Pseudomonas aeruginosa increased COX-2 transcriptional activity. Furthermore, YY1
      enhanced COX-2 protein expression and prostaglandin D(2) production elicited by
      LPS treatment. Mechanistically, we observed that LPS treatment resulted in
      disruption of an interaction between YY1 and p300, a histone acetyltransferase,
      but did not affect the interaction between YY1 and histone deacetylase 1/2. These
      data suggest that in response to LPS, YY1 dissociates from p300 and binds to the
      COX-2 promoter, contributing to COX-2 expression in an inflammatory milieu.

PMID- 17220376
TI  - Atropine pretreatment enhances airway hyperreactivity in antigen-challenged
      guinea pigs through an eosinophil-dependent mechanism.
AB  - Airway hyperreactivity in antigen-challenged animals is mediated by eosinophil
      major basic protein (MBP) that blocks inhibitory M(2) muscarinic receptors on
      parasympathetic nerves, increasing acetylcholine release onto M(3) muscarinic
      receptors on airway smooth muscle. Acutely, anticholinergics block
      hyperreactivity in antigen-challenged animals and reverse asthma exacerbations in
      the human, but are less effective in chronic asthma. We tested whether atropine,
      given before antigen challenge, affected hyperreactivity, M(2) receptor function,
      eosinophil accumulation, and activation. Sensitized guinea pigs received atropine
      (1 mg/kg ip) 1 h before challenge and 6 h later. Twenty-four hours after
      challenge, animals were anesthetized, vagotomized, paralyzed, and ventilated.
      Airway reactivity to electrical stimulation of the vagi and to intravenous
      acetylcholine was not altered by atropine pretreatment in nonsensitized animals,
      indicating that atropine was no longer blocking postjunctional muscarinic
      receptors. Antigen challenge induced airway hyperreactivity to vagal stimulation
      that was significantly potentiated by atropine pretreatment. Bronchoconstriction
      induced by acetylcholine was not changed by antigen challenge or by atropine
      pretreatment. M(2) receptor function was lost in challenged animals but protected
      by atropine pretreatment. Eosinophils in bronchoalveolar lavage and within airway
      tissues were significantly increased by challenge but significantly reduced by
      atropine pretreatment. However, extracellular MBP in challenged airways was
      significantly increased by atropine pretreatment, which may account for reduced
      eosinophils. Depleting eosinophils with antibody to IL-5 before challenge
      prevented hyperreactivity and significantly reduced MBP in airways of atropine
      pretreated animals. Thus atropine pretreatment potentiated airway hyperreactivity
      by increasing eosinophil activation and degranulation. These data suggest that
      anticholinergics enhance eosinophil interactions with airway nerves.

PMID- 17220378
TI  - Distinguished Contribution to Family Nursing Award: Dr. Lorraine M. Wright and
      Dr. Maureen Leahey for: Wright, L. M., & Leahey, M. Nurses and families: a guide
      to family assessment and intervention (1984, 1994, 2000, 2005).

PMID- 17220377
TI  - A murine respiratory-inducing niche displays variable efficiency across human and
      mouse embryonic stem cell species.
AB  - Human embryonic stemlike cells (hESCs) are pluripotent cells derived from
      blastocysts. Differentiating hESCs into respiratory lineages may benefit
      respiratory therapeutic programs. We previously demonstrated that 24% of all
      mouse embryonic stem cell (mESC) derivatives cocultured with embryonic day 11.5
      (E11.5) mouse lung rudiments display immunoreactivity to the pneumonocyte II
      specific marker surfactant-associated protein C (Sftpc). Here we further
      investigate the effects of this inductive niche in terms of its competence to
      induce hESC derivative SFTPC immunoreactivity and the expression of other markers
      of terminal lung secretory units. When hESCs were cocultured as single cells,
      clumps of approximately 10 cells or embryoid bodies (EBs), hESC derivatives
      formed pan-keratin-positive epithelial tubules at high frequency (>30% of all
      hESC derivatives). However, human-specific SFTPC immunoreactivity associated with
      tubule formation only at low frequency (<0.1% of all hESC derivatives). Human
      specific SFTPD and secretoglobin family 1A member 1 (SCGB1A1, also known as CC10)
      transcripts were detected by PCR after prolonged culture. Expression of other
      terminal lung secretory unit markers (TITF1, SFTPA, and SFTPB) was not detected
      at any time point analyzed. On the other hand, hESC derivatives cultured as
      plated EBs in media previously demonstrated to induce Sftpc expression in
      isolated mouse fetal tracheal epithelium expressed all terminal lung secretory
      unit markers examined. mESCs and hESCs thus display fundamental differences in
      their response to the E11.5 mouse lung inductive niche, and these data provide an
      important step in the delineation of signaling mechanisms capable of efficiently
      inducing hESC differentiation into terminal secretory units of the lung.

PMID- 17220379
TI  - Distinguished Contribution to Family Nursing Award: Dr. Lorraine M. Wright and
      Dr. Maureen Leahey for: Wright, L. M., & Leahey, M. Nurses and families: a guide
      to family assessment and intervention (1984, 1994, 2000, 2005).

PMID- 17220380
TI  - Mother-adult daughter relationships within dementia care: a critical analysis.
AB  - Evidence suggests that intergenerational caregiving between mothers and daughters
      will become increasingly common, and yet, we know very little about the specific
      relationships between adult daughters and their mothers with dementia. Guided by
      socialist-feminist theory and a life-course perspective, 15 mother-adult daughter
      dyads participated in two individual, semistructured interviews. Data analysis
      revealed four dynamic types of mother-daughter relationships: custodial,
      combative, cooperative, and cohesive. Custodial and cooperative relationships
      mainly focused on the provision of and receipt of tasks, whereas combative and
      cohesive are emotion focused. At the same time, custodial and combative
      relationships are based on deficits compared with strength based cohesive and
      cooperative relationships. In addition, certain contextual factors, such as
      expectations of care and levels of support, shaped the development of these
      relationships. Moreover, study findings highlight a number of implications for
      practice, policy, and research necessary to support individuals with dementia and
      their families.

PMID- 17220381
TI  - Meaning and action in employed mothers' health work.
AB  - The purpose of this critical feminist study was to examine employed mothers'
      meanings of family and personal health as they frame the context of daily
      experience in caring for their families' and their own health. Twenty mothers
      employed in support staff positions with a large institution in Western Canada
      participated in repeat interviews over 2 years. Women considered individual
      family members and the family group as they emphasized everyday function and
      satisfaction, and the presence or absence of various attributes of health as a
      multifaceted and dynamic experience. Women's health work included keeping track,
      constructing routines, facing challenges, setting priorities, being there for
      each other, finding joy and fulfillment, and fostering personal development. A
      preliminary typology of four orientations to family health work is suggested.
      Common themes between women's and family health and congruence between women's
      health meanings and actions provide guidance to nurses in family health promotion
      practice.

PMID- 17220382
TI  - Imposing order: a process to manage day-to-day activities in two-earner families
      with preschool children.
AB  - This study investigated how English and Canadian families with preschool children
      used strategies to impose varying levels of order to manage day-to-day
      activities. This grounded theory study is a secondary analysis of 55 hours of
      participant observation and interviews with 58 individuals and 29 couples.
      Constant comparative analysis and theoretical sampling were used to construct
      categories. To attempt to impose order, strategies used by families included
      organizing and planning, establishing routines, setting limits, setting
      standards, purchasing services and technology, and delegating tasks. Most
      families used these strategies successfully; costs outweighed benefits where
      families concentrated inflexibly on a few strategies in particular spheres of
      activity or had difficulty using strategies. Families using a variety of
      strategies flexibly were better at balancing personal and family goals, promoting
      fulfillment, health, and happiness for each family member, and fostering family
      development and commitment. Imposing order links everyday family dynamics and
      concerns to long-term goals.

PMID- 17220383
TI  - Parent as proxy reporting: implications and recommendations for quality of life
      research.
AB  - Improved disease management in children has resulted in an increased interest in
      the quality of life in children. Quality of life research in children may enlist
      either the substitute or complementary perspective. Much of the quality of life
      literature has been guided by the substitute perspective, which infers that
      parents may best report their child's quality of life. However, the complementary
      perspective values both parent and child perspectives equally. The purpose of
      this article was to critically review the quality of life literature with respect
      to children with diabetes. Limitations in the literature were addressed as
      conceptual and methodological, demographic, and underlying proxy perspectives.
      Benefits and limitations of quality of life measurements and perspectives were
      also discussed. Recommendations and future implications for quality of life
      research in children extend current understanding from both substitute and
      complementary perspectives.

PMID- 17220384
TI  - Restructuring life: preparing for and beginning a new caregiving role.
AB  - Family caregivers of stroke survivors who are just beginning their role must
      learn new skills and incorporate new knowledge into their daily activities. This
      can be a time of increased anxiety and stress for them. Nurses and other health
      professionals need more knowledge about this transition from the perspective of
      the caregivers. The purpose of this grounded theory study was to describe the
      process associated with preparing for and beginning a new caregiving role
      following a family member's stroke. Caregivers who were new to the role were
      interviewed prior to the stroke survivor's discharge and 4 weeks after discharge.
      The grounded theory, Restructuring Life for Caregiving, was associated with five
      dimensions of participants' lives: daily life, managing multiple roles,
      relationship with the stroke survivor, future hopes and plans, and time for self.
      The process of waiting, rearranging, and stabilizing further explained the timing
      and elements of restructuring activities.

PMID- 17220385
TI  - The soul of sorrow work: grief and therapeutic interventions with families.
AB  - The courage and willingness to walk alongside families in grief calls forth
      particular beliefs and practices in nurses and other health care professionals.
      In this second phase of a study on grief and grief interventions, the researchers
      examine experiences of bereaved family members who received care in a grief
      support program and explore program clinicians'explanations of the work that they
      do with the bereaved. Findings of this interpretive study suggest that it is not
      so much models of grief intervention but maps that most guide the clinicians-
      maps that are drawn out of experience and with awareness of their limitations.
      The family members and the clinicians bring us to an understanding that, often,
      it is the willingness to step off of the map that makes for the best traveling
      companion in the spiritual walk of grief.

PMID- 17220386
TI  - Quantitative influences on the presentation of qualitative articles.

PMID- 17220387
TI  - Men, masculinities, and prostate cancer: Australian and Canadian patient
      perspectives of communication with male physicians.
AB  - Patient-physician communication is vital in cancer care, and aspects of the
      patients' experiences provide insight into what constitutes effective cancer
      communication. Complexities inherent in prostate cancer regarding screening,
      treatment(s) efficacy, and side effects commonly form the basis of patient
      physician discussions. However, the specificities of patient-physician
      communications, particularly in the male dyad, and the connections to masculinity
      are poorly understood. The authors used secondary analysis of data from two
      interview studies of 19 Canadian and 33 Australian prostate cancer survivors who
      were treated by male general practitioners and prostate cancer specialists.
      Participants acknowledged that physician expertise and compassion underpinned the
      development of trust, and both reassurance and humor were effective communication
      strategies. Participants were often self-directed in researching prostate cancer,
      consistently using biomedical language and numerical markers when discussing
      their disease. Analysis of findings enabled interpretations regarding what might
      be considered prostate cancer communication competencies in the male patient
      physician dyad.

PMID- 17220388
TI  - Identity and resilience among persons with HIV: a rural African American
      experience.
AB  - In this article, the author contrasts the disruption model proposed by Becker
      (1997) against the life trajectories of two persons who used and sold drugs;
      considers the impact of engagement and discontinuation of substance use on their
      respective lives; and examines the process of life reorganization they put into
      motion after testing positive for HIV. Their departure from the world of drugs
      removed each from an unwanted lifestyle, facilitated the process of building
      resilience against the social adversity they faced in relation to their
      seropositivity, assisted them with securing care and services through
      institutional mechanisms, and generated a forum for new ideas on family
      continuity versus the ideal of individualism that grounds mainstream society. A
      process of identity reaffirmation further deepened their understanding of
      themselves as African Americans in the southern United States.

PMID- 17220389
TI  - Spirituality in African Americans with diabetes: self-management through a
      relationship with God.
AB  - The purpose of this study was to develop a theoretical model about how the
      spirituality of African Americans affects their self-management of diabetes. The
      sample consisted of 29 African American men and women, ages 40 to 75, with type 2
      diabetes. The authors used a grounded theory design and collected data using
      minimally structured interviews. The method of analysis was constant comparison.
      The core concept identified was Self-Management Through a Relationship With God.
      Participants fell into one of three typologies: (a) Relationship and
      Responsibility: God Is in Background; (b) Relationship and Responsibility: God Is
      in Forefront: (c) Relationship and Relinquishing of Self-Management: God Is
      Healer. These typologies varied according to how participants viewed their
      relationship with God and the impact of this relationship on their self
      management. The spirituality of these African Americans was an important factor
      that influenced the self-management of their diabetes.

PMID- 17220390
TI  - Negotiating sexual agency: postmenopausal women's meaning and experience of
      sexual desire.
AB  - The purpose of this feminist grounded theory study was to understand the meaning
      and experience of postmenopausal women's sexual desire. Data collection from 22
      postmenopausal women who were ongoing participants of the TREMIN Research Program
      on Women's Health occurred via audiotaped, telephone-based, semistructured
      interviews. Women's descriptions of their sexual needs and desires led to the
      discovery of the core category, negotiating sexual agency, which refers to
      women's ability to act on behalf of their sexual needs, desires, and wishes.
      Women negotiated their sexual agency within three main domains (or axial codes):
      their own sexual self, their partners, and the medical system. An important
      finding was women's internalization of sociocultural assumptions that privilege
      their male partners' sexual needs over their own. The findings of this study,
      especially the contexts in which women negotiate their sexual agency, are
      important for women, women's health care providers, and women's life partners to
      understand.

PMID- 17220391
TI  - Adolescents' perceptions of inpatient postpartum nursing care.
AB  - The authors used a transcendental phenomenological approach to describe
      adolescent mothers' satisfactory and unsatisfactory inpatient postpartum nursing
      care experiences. They analyzed data from 14 in-depth interviews and found that
      adolescent mothers' satisfaction is dependent on their perceptions of the nurse's
      ability to place them "at ease." Nursing care qualities that contributed to
      satisfactory experiences included nurses' sharing information about themselves,
      being calm, demonstrating confidence in mothers, speaking to adolescent and adult
      mothers in the same way, and anticipating unstated needs. Nursing care was
      perceived to be unsatisfactory when it was too serious, limited to the job
      required, or different from care to adult mothers, or when nurses failed to
      recognize individual needs. In extreme cases, unsatisfactory experiences hindered
      development of an effective nurse-client relationship. These findings illustrate
      the value of qualitative inquiry for understanding patients' satisfaction with
      care, can be used for self-reflection, and have implications for nursing
      education programs.

PMID- 17220392
TI  - Experiences of living with non-cancer-related lymphedema: implications for
      clinical practice.
AB  - Lymphedema is a chronic medical condition caused by lymphatic insufficiency that
      can lead to extreme swelling and susceptibility to infection. Physical and
      psychosocial effects of the condition can have a significant impact on an
      individual's life and level of participation. Research about experiences of
      individuals living with lymphedema has focused primarily on women with breast
      cancer, yet individuals with non-cancer-related lymphedema are a distinct group.
      In this study, the authors used qualitative description to explore the experience
      of 7 individuals living with advanced and complicated cases of lymphedema who had
      been treated in an inpatient setting. Findings reveal the extensive impact
      lymphedema has on those who live with it. Participants spoke of difficulty
      finding a correct diagnosis and effective treatment, the importance of their
      inpatient experiences, and the challenges of daily self-management. The authors
      make recommendations to increase lymphedema awareness, promote inpatient
      treatment programs, and create effective self-management techniques.

PMID- 17220393
TI  - Community social support for Cuban refugees in Texas.
AB  - Social support has been linked to positive health outcomes for many populations
      across multiple health issues. The interactional approach defines social support
      as a complex, transactional process between the person and his or her social
      environment. Being part of a community enhances the likelihood of social bonding,
      leading to increased perceived support. In this study, the authors describe
      recently arrived adult Cuban refugees' perceptions of community-level support in
      Texas. Practical and emotional support needs included jobs and companionship away
      from everyday problems. The two major sources of practical support were
      resettlement agencies and other Cubans. The two major sources of emotional
      support were other Cubans and English-speaking friends. There were no local Cuban
      clubs or associations where Cubans could meet. Besides receiving support, many
      Cubans were also supporting other Cubans locally and in Cuba, and some
      experienced discrimination.

PMID- 17220394
TI  - Children talking: emerging perspectives and experiences of cigarette smoking.
AB  - Despite efforts to prevent the onset of smoking, the rate among older children
      remains high. In this article, the authors report on a longitudinal, qualitative
      study of 11 to 16-year-old children describing children's construction of what it
      means to be a smoker, the reasons given for children smoking, and their views of
      smoking behavior. Findings indicate that children adopt broad interpretations of
      what constitutes smoking behavior; although they strongly disapprove of children
      who smoke, they are less disapproving of older children or adult smokers and are
      increasingly tolerant of smoking behavior as they get older. Children's
      disapproval of smoking acts as a protective mechanism against smoking for younger
      participants. Participants' broad interpretation of what it means to be a
      cigarette smoker, their association of smoking with adulthood, and their
      increasing tolerance of and exposure to smoking behavior as they move into
      adolescence appears to increase susceptibility to becoming cigarette smokers.

PMID- 17220395
TI  - Children's attitudes toward people with AIDS in Puerto Rico: exploring stigma
      through drawings and stories.
AB  - AIDS stigma refers to prejudice and discrimination directed at people or groups
      perceived to have HIV/AIDS (Herek, 1999). Although AIDS stigma has been found in
      adolescent and adult populations, few researchers have explored it among
      children. Misconceptions about people with AIDS (PWA) might lead to negative
      attitudes toward PWA and obstruct HIV prevention efforts. The authors assessed
      110 Puerto Rican children's attitudes toward PWA using drawings (n=65) and
      stories (n=45). Although participants held stigmatizing attitudes toward PWA
      across both methods, the approaches captured different beliefs and attitudes.
      Drawings depicted PWA as physically deteriorated and performing socially
      condemned behaviors, whereas stories describing PWA highlighted children's fear
      of contagion and death. Stigma toward PWA was more pronounced than toward other
      illnesses (e.g., cancer). The study highlights the importance of assessing
      children's attitudes through creative data collection procedures.

PMID- 17220396
TI  - Confidentiality and autonomy: the challenge(s) of offering research participants
      a choice of disclosing their identity.
AB  - In this article, the authors present one of the key ethical features of research:
      confidentiality as maintained by nondis-closure of participants' identities. In
      light of (a) the contingency that certain participants might vest interest in
      research studies through their identity and (b) the concept of respect for
      participants' autonomy, the authors consider the possibilities of offering
      research participants the choice of nonconfidentiality, afforded as an autonomous
      (negative) right of refusal of nondisclosure of identity. They address the issue
      that this possibility generates within the context(s) of current codes of ethics
      related to health research and the manifest responsibilities of the institutional
      review process. In this way, they attempt to elucidate potential benefits and
      consequences that arise from confidentiality and nonconfidentiality.

PMID- 17220397
TI  - Learning from the grandmothers: incorporating indigenous principles into
      qualitative research.
AB  - In this article, the author describes the process she undertook to incorporate
      Indigenous principles into her doctoral research about the midlife health
      experiences of elder Aboriginal women in Nova Scotia, Canada. By employing
      qualitative methods within the context of an Indigenous worldview, she gained
      knowledge of and developed competence in Aboriginal health research. The emergent
      partnership among Aboriginal community research facilitators, participating
      Mi'kmaq women, and the researcher provided many opportunities for the researcher
      to incorporate the paradigmatic and methodological traditions of Western science
      and Indigenous cultures. The application of these principles to this study might
      provide a useful example for other health researchers who are attempting to
      incorporate diverse methodological principles.

PMID- 17220398
TI  - ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium
      scoring by computed tomography in global cardiovascular risk assessment and in
      evaluation of patients with chest pain: a report of the American College of
      Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing
      Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed
      Tomography).

PMID- 17220399
TI  - Combination of tigecycline and N-acetylcysteine reduces biofilm-embedded bacteria
      on vascular catheters.
AB  - To assess the efficacy of an antibiofilm/antimicrobial agent combination, we
      incubated catheter segments colonized with one of six studied bacterial organisms
      in N-acetylcysteine, tigecycline, N-acetylcysteine-tigecycline, or saline.
      Segments were washed, sonicated, and cultured. N-acetylcysteine-tigecycline
      significantly decreased all viable biofilm-associated bacteria and was
      synergistic for methicillin-resistant Staphylococcus aureus and Staphylococcus
      epidermidis.

PMID- 17220400
TI  - In vitro inhibition of Streptococcus mutans biofilm formation on hydroxyapatite
      by subinhibitory concentrations of anthraquinones.
AB  - We report that certain anthraquinones (AQs) reduce Streptococcus mutans biofilm
      formation on hydroxyapatite at concentrations below the MIC. Although AQs are
      known to generate reactive oxygen species, the latter do not underlie the
      observed effect. Our results suggest that AQs inhibit S. mutans biofilm formation
      by causing membrane perturbation.

PMID- 17220401
TI  - Gamma interferon loaded onto albumin nanoparticles: in vitro and in vivo
      activities against Brucella abortus.
AB  - The aim of this study was to evaluate the activity of gamma interferon (IFN
      gamma) when it was either adsorbed onto or loaded into albumin nanoparticles.
      Brucella abortus-infected macrophages and infected BALB/c mice were selected as
      the models for testing of the therapeutic potentials of these cytokine delivery
      systems, in view of the well-established role of IFN-gamma-activated macrophages
      for the control of Brucella sp. infections. Whereas the encapsulation of IFN
      gamma inside the matrix of nanoparticles completely abrogated its activity,
      adsorbed IFN-gamma increased by 0.75 log unit the bactericidal effect induced by
      RAW macrophages activated with free IFN-gamma, along with a higher level of
      production of nitric oxide. In infected BALB/c-mice, IFN-gamma adsorbed onto
      nanoparticles was also more active than free cytokine in reducing the number of
      bacteria in the spleens, and the effect was mediated by an increased ratio of IFN
      gamma-secreting (Th1) to interleukin-4-secreting (Th2) cells. Overall, albumin
      nanoparticles would be suitable as carriers that target IFN-gamma to macrophages
      and, thus, potentiate their therapeutic activity.

PMID- 17220402
TI  - Activity of daptomycin alone and in combination with rifampin and gentamicin
      against Staphylococcus aureus assessed by time-kill methodology.
AB  - The synergistic effects of daptomycin plus gentamicin or rifampin were tested
      against 50 Staphylococcus aureus strains, with daptomycin MICs ranging between
      0.25 and 8 microg/ml. Daptomycin sub-MICs combined with gentamicin concentrations
      lower than the MIC yielded synergy in 34 (68%) of the 50 strains. Daptomycin
      combined with rifampin yielded synergy in one vancomycin-intermediate S. aureus
      strain only, and virtually all synergy occurred between daptomycin and
      gentamicin.

PMID- 17220403
TI  - Zidovudine inhibits thymidine phosphorylation in the isolated perfused rat heart.
AB  - Zidovudine (AZT; 3'-azido-3'-deoxythymidine), a thymidine analog, has been a
      staple of highly active antiretroviral therapy. It is phosphorylated in the host
      to the triphosphate and functions by inhibiting the viral reverse transcriptase.
      However, long-term use of AZT is linked to various tissue toxicities, including
      cardiomyopathy. These toxicities are associated with mitochondrial DNA depletion,
      which is hypothesized to be caused by AZT triphosphate inhibition of
      mitochondrial DNA polymerase gamma. In previous work with isolated heart
      mitochondria, we demonstrated that AZT phosphorylation beyond the monophosphate
      was not detected and that AZT itself was a potent inhibitor of thymidine
      phosphorylation. This suggests an alternative hypothesis in which depletion of
      the TTP pool may limit mitochondrial DNA replication. The present work extends
      these studies to the whole cell by investigating the metabolism of thymidine and
      AZT in the intact isolated perfused rat heart. [3H]thymidine is converted to
      [3H]TTP in a time- and concentration-dependent manner. The level of [3H]TMP is
      low, suggesting that the reaction catalyzed by thymidine kinase is the rate
      limiting step in phosphorylation. [3H]AZT is converted in a time- and
      concentration-dependent manner to AZT monophosphate, the only phosphorylated
      product detected after 3 h of perfusion. Both compounds display negative
      cooperativity, similar to the observations with cloned and purified mitochondrial
      thymidine kinase 2. The presence of AZT in the perfusate inhibits the
      phosphorylation of [3H]thymidine with a 50% inhibitory concentration of 24+/-4
      microM. These data support the hypothesis that AZT-induced mitochondrial
      cardiotoxicity may be caused by a limiting pool of TTP that lowers mitochondrial
      DNA replication.

PMID- 17220404
TI  - Increased genome instability in Escherichia coli lon mutants: relation to
      emergence of multiple-antibiotic-resistant (Mar) mutants caused by insertion
      sequence elements and large tandem genomic amplifications.
AB  - Thirteen spontaneous multiple-antibiotic-resistant (Mar) mutants of Escherichia
      coli AG100 were isolated on Luria-Bertani (LB) agar in the presence of
      tetracycline (4 microg/ml). The phenotype was linked to insertion sequence (IS)
      insertions in marR or acrR or unstable large tandem genomic amplifications which
      included acrAB and which were bordered by IS3 or IS5 sequences. Five different
      lon mutations, not related to the Mar phenotype, were also found in 12 of the 13
      mutants. Under specific selective conditions, most drug-resistant mutants
      appearing late on the selective plates evolved from a subpopulation of AG100 with
      lon mutations. That the lon locus was involved in the evolution to low levels of
      multidrug resistance was supported by the following findings: (i) AG100 grown in
      LB broth had an important spontaneous subpopulation (about 3.7x10(-4)) of
      lon::IS186 mutants, (ii) new lon mutants appeared during the selection on
      antibiotic-containing agar plates, (iii) lon mutants could slowly grow in the
      presence of low amounts (about 2x MIC of the wild type) of chloramphenicol or
      tetracycline, and (iv) a lon mutation conferred a mutator phenotype which
      increased IS transposition and genome rearrangements. The association between lon
      mutations and mutations causing the Mar phenotype was dependent on the medium (LB
      versus MacConkey medium) and the antibiotic used for the selection. A previously
      reported unstable amplifiable high-level resistance observed after the prolonged
      growth of Mar mutants in a low concentration of tetracycline or chloramphenicol
      can be explained by genomic amplification.

PMID- 17220405
TI  - Resistance to glycopeptide antibiotics in the teicoplanin producer is mediated by
      van gene homologue expression directing the synthesis of a modified cell wall
      peptidoglycan.
AB  - Glycopeptide resistance has been studied in detail in enterococci and
      staphylococci. In these microorganisms, high-level resistance is achieved by
      replacing the C-terminal D-alanyl-D-alanine of the nascent peptidoglycan with D
      alanyl-D-lactate or D-alanyl-D-serine, thus reducing the affinities of
      glycopeptides for cell wall targets. Reorganization of the cell wall is directed
      by the expression of the van gene clusters. The identification of van gene
      homologs in the genomes of several glycopeptide-producing actinomycetes suggests
      the involvement of a similar self-resistance mechanism to avoid suicide. This
      report describes a comprehensive study of self-resistance in Actinoplanes
      teichomyceticus ATCC 31121, the producer of the clinically relevant glycopeptide
      teicoplanin. A. teichomyceticus ATCC 31121 showed a MIC of teicoplanin of 25
      microg/ml and a MIC of vancomycin of 90 microg/ml during vegetative growth. The
      vanH, vanA, and vanX genes of A. teichomyceticus were found to be organized in an
      operon whose transcription was constitutive. Analysis of the UDP-linked
      peptidoglycan precursors revealed the presence of UDP-glycomuramyl
      pentadepsipeptide terminating in D-alanyl-D-lactate. No trace of precursors
      ending in d-alanyl-d-alanine was detected. Thus, the van gene complex was
      transcribed and expressed in the genetic background of A. teichomyceticus and
      conferred resistance to vancomycin and teicoplanin through the modification of
      cell wall biosynthesis. During teicoplanin production (maximum productivity, 70
      to 80 microg/ml), the MIC of teicoplanin remained in the range of 25 to 35
      microg/ml. Teicoplanin-producing cells were found to be tolerant to high
      concentrations of exogenously added glycopeptides, which were not bactericidal
      even at 5,000 microg/ml.

PMID- 17220406
TI  - Mosaic structure of p1658/97, a 125-kilobase plasmid harboring an active amplicon
      with the extended-spectrum beta-lactamase gene blaSHV-5.
AB  - Escherichia coli isolates recovered from patients during a clonal outbreak in a
      Warsaw, Poland, hospital in 1997 produced different levels of an extended
      spectrum beta-lactamase (ESBL) of the SHV type. The beta-lactamase
      hyperproduction correlated with the multiplication of ESBL gene copies within a
      plasmid. Here, we present the complete nucleotide sequence of plasmid p1658/97
      carried by the isolates recovered during the outbreak. The plasmid is 125,491 bp
      and shows a mosaic structure in which all modules constituting the plasmid core
      are homologous to those found in plasmids F and R100 and are separated by
      segments of homology to other known regions (plasmid R64, Providencia rettgeri
      genomic island R391, Vibrio cholerae STX transposon, Klebsiella pneumoniae or E.
      coli chromosomes). Plasmid p1658/97 bears two replication systems, IncFII and
      IncFIB; we demonstrated that both are active in E. coli. The presence of an
      active partition system (sopABC locus) and two postsegregational killing systems
      (pemIK and hok/sok) indicates that the plasmid should be stably maintained in E.
      coli populations. The conjugative transfer is ensured by the operons of the tra
      and trb genes. We also demonstrate that the plasmidic segment undergoing
      amplification contains the blaSHV-5 gene and is homologous to a 7.9-kb fragment
      of the K. pneumoniae chromosome. The amplicon displays the structure of a
      composite transposon of type I.

PMID- 17220407
TI  - Population structure and resistance genes in antibiotic-resistant bacteria from a
      remote community with minimal antibiotic exposure.
AB  - In a previous study, we detected unexpectedly high levels of acquired antibiotic
      resistance in commensal Escherichia coli isolates from a remote Guarani Indian
      (Bolivia) community with very low levels of antibiotic exposure and limited
      exchanges with the exterior. Here we analyzed the structure of the resistant E.
      coli population from that community and the resistance mechanisms. The E. coli
      population (113 isolates from 72 inhabitants) showed a high degree of genetic
      heterogeneity, as evidenced by phylogenetic grouping (77% group A, 10% group B1,
      8% group D, 5% group B2) and genotyping by randomly amplified polymorphic DNA
      (RAPD) analysis (44 different RAPD types). The acquired resistance genes were
      always of the same types as those found in antibiotic-exposed settings [blaTEM,
      blaPSE-1, catI, cmlA6, tet(A), tet(B), dfrA1, dfrA7, dfrA8, dfrA17, sul1, sul2,
      aphA1, aadA1, aadA2, aadA5, aadB, and sat-1]. Class 1 and class 2 integrons were
      found in 12% and 4% of the isolates, respectively, and harbored arrays of gene
      cassettes similar to those already described. The cotransferability of multiple
      resistance traits was observed from selected isolates and was found to be
      associated with resistance conjugative plasmids of the F, P, and N types.
      Overall, these data suggest that the resistance observed in this remote community
      is likely the consequence of the dissemination of resistant bacteria and
      resistance genes from antibiotic-exposed settings (rather than of an independent
      in situ selection) which involved both the clonal expansion of resistant strains
      and the horizontal transfer/recombination of mobile genetic elements harboring
      resistance genes.

PMID- 17220408
TI  - The Anti-Trypanosoma cruzi activity of posaconazole in a murine model of acute
      Chagas' disease is less dependent on gamma interferon than that of benznidazole.
AB  - We have investigated the influences of gamma interferon (IFN-gamma) and
      interleukin-12 (IL-12) on the efficacy of posaconazole (POS) treatment of acute
      experimental infections with Trypanosoma cruzi; the standard drug, benznidazole
      (BZ), was used as a positive control. Wild-type (WT) mice infected with T. cruzi
      and treated with POS or BZ had no parasitemia, 100% survival, and cure rates of
      86 to 89%. IFN-gamma-knockout (KO) mice infected with T. cruzi and treated with
      BZ controlled the infection during treatment but relapsed after the drug pressure
      ceased and had 0% survival, while those receiving POS better controlled the
      infection after the end of treatment and had 70% survival (P<0.0001 compared to
      the results for both untreated and BZ-treated animals). IL-12-KO mice infected
      and treated with POS or BZ had intermediate results, displaying enhanced
      parasitemia, decreased survival (77 to 83%), and reduced cure rates (35 to 39%)
      compared with those of the WT animals. Our results demonstrate that either IFN
      gamma or IL-12 deficiency reduces the efficacy of POS or BZ in this experimental
      model but also indicate that the anti-T. cruzi activity of POS is much less
      dependent on the activity of IFN-gamma than that of BZ is.

PMID- 17220409
TI  - Population pharmacokinetic model for gatifloxacin in pediatric patients.
AB  - The broad spectrum of antimicrobial activity, oral bioavailability, extensive
      tissue distribution, and once-daily intravenous or oral dosing of gatifloxacin,
      an expanded-spectrum 8-methoxy fluoroquinolone, make it a potentially useful
      agent for the treatment of pediatric infections. A population pharmacokinetic
      model was developed to describe the pharmacokinetics of gatifloxacin in children.
      Data for analysis were obtained from a single-dose safety/pharmacokinetic study
      utilizing intensive blood sampling in patients aged 6 months to 16 years. Each
      subject received a single oral dose of gatifloxacin as a suspension, at doses of
      5, 10, or 15 mg/kg of body weight. A total of 845 samples were obtained from 82
      patients. A one-compartment model with first-order absorption and elimination was
      the most appropriate to describe the gatifloxacin concentrations. Covariate
      analysis using forward selection and backward elimination found that apparent
      clearance was related to body surface area, and apparent volume of distribution
      was related to body weight. No effect of age on drug clearance could be
      identified once clearance was corrected for body surface area. Based on
      pharmacokinetic simulations, the 10-mg/kg (maximum, 400 mg) once-daily dose of
      gatifloxacin is expected to provide drug exposure similar to that in healthy
      adults. The population pharmacokinetic model described herein will be used for
      Bayesian analyses of sparse pharmacokinetic sampling in phase II/III clinical
      trials and for Monte Carlo simulation experiments. The success of this strategy
      provides a model for future pediatric drug development programs.

PMID- 17220410
TI  - Use of novel boronic acid transition state inhibitors to probe substrate affinity
      in SHV-type extended-spectrum beta-lactamases.
AB  - Boronic acid transition state inhibitors (BATSIs) with R1 side chains of
      cefotaxime and ceftazidime were assayed against SHV-1, SHV-2, SHV-5, D104K, and
      D104K G238S beta-lactamases. The D104K variant was the most susceptible to
      inhibition by the ceftazidime BATSI (Ki, 730+/-80 nM), while the D104K G238S
      variant was the most susceptible to the cefotaxime BATSI (Ki, 1.1+/-0.2 microM).

PMID- 17220411
TI  - Bactericidal activity and resistance development profiling of dalbavancin.
AB  - Dalbavancin, a semisynthetic lipoglycopeptide being developed for the treatment
      of skin and skin structure infections (SSSIs), has a half-life of 5 to 7 days in
      humans and offers promise for a convenient weekly dosing regimen. We studied the
      in vitro bactericidal activity of dalbavancin against target organisms, using the
      concentrations that are maintained in human blood with the proposed dosage
      regimen. Dalbavancin minimal bactericidal concentrations (MBCs) were<or=0.5
      microg/ml for eight staphylococcal isolates; and for six of these strains,
      including one vancomycin-intermediate Staphylococcus aureus (VISA) isolate, the
      MBCs were equal to or within 1 doubling dilution of the MIC. Dalbavancin MICs for
      all three Streptococcus pyogenes strains were 0.008 microg/ml, as were the MBCs
      for two of the isolates. In time-kill studies conducted with a different set of
      seven strains (two methicillin-susceptible S. aureus isolates, three methicillin
      resistant S. aureus isolates, one VISA isolate, and one S. pyogenes isolate), all
      strains exhibited a>or=3-log10 decrease in their viable counts when they were
      exposed to>or=1 microg/ml of dalbavancin for 24 h. Resistance development studies
      by both direct selection (resistance frequency, <10(-10)) and serial passage
      failed to produce stable mutants with decreased susceptibility to dalbavancin.
      These observations suggest that dalbavancin will be an effective choice for the
      management of patients with SSSIs.

PMID- 17220412
TI  - Evolution of TEM-type enzymes: biochemical and genetic characterization of two
      new complex mutant TEM enzymes, TEM-151 and TEM-152, from a single patient.
AB  - Two clinical isolates of Escherichia coli, CF1179 and CF1295, were isolated from
      a patient hospitalized in the hematology unit of the University Hospital of
      Clermont-Ferrand, Clermont-Ferrand, France. They were resistant to penicillin
      clavulanate combinations and to ceftazidime. The double-disk synergy test was
      positive only for isolate CF1179. Molecular comparison of the isolates showed
      that they were clonally related. E. coli recombinant strains exhibiting the
      resistance phenotype of the clinical strains were obtained by cloning. The clones
      corresponding to strains CF1179 and CF1295 produced TEM-type beta-lactamases with
      pI values of 5.7 and 5.3, respectively. Sequencing analysis revealed two novel
      blaTEM genes encoding closely related complex mutant TEM enzymes, designated TEM
      151 (pI 5.3) and TEM-152 (pI 5.7). These two genes also harbored a new promoter
      region which presented a 9-bp deletion. The two novel beta-lactamases differed
      from the parental enzyme, TEM-1, by the substitution Arg164His, previously
      observed in extended-spectrum beta-lactamases (ESBLs), and by the substitutions
      Met69Val and Asn276Asp, previously observed in the inhibitor-resistant
      penicillinase TEM-36/IRT-7. They differed by two amino acid substitutions: TEM
      152 harbored a Glu240Lys ESBL-type substitution and TEM-151 had an Ala284Gly
      substitution. Functional analysis of TEM-151 and TEM-152 showed that both enzymes
      had hydrolytic activity against ceftazidime (kcat, 5 and 16 s-1, respectively).
      TEM-152 was more resistant than TEM-151 to the inhibitor clavulanic acid (50%
      inhibitory concentrations, 1 versus 0.17 microM). These results confirm the
      evolution of TEM-type enzymes toward complex enzymes harboring the two kinds of
      substitutions which confer an extended spectrum of action against beta-lactam
      antibiotics and resistance to inhibitors.

PMID- 17220413
TI  - Reduced susceptibility of Haemophilus influenzae to the peptide deformylase
      inhibitor LBM415 can result from target protein overexpression due to amplified
      chromosomal def gene copy number.
AB  - Previous genetic analysis of Haemophilus influenzae revealed two mechanisms
      associated with decreased susceptibility to the novel peptide deformylase
      inhibitor LBM415: AcrAB-TolC-mediated efflux and Fmt bypass, resulting from
      mutations in the pump repressor gene acrR and in the fmt gene, respectively. We
      have isolated an additional mutant, CDS23 (LBM415 MIC, 64 microg/ml versus 4
      microg/ml against the parent strain NB65044) that lacks mutations in the acrR or
      fmt structural genes or in the gene encoding Def, the intracellular target of
      LBM415. Western immunoblot analysis, two-dimensional gel electrophoresis, and
      tryptic digestion combined with mass spectrometric identification showed that the
      Def protein was highly overexpressed in the mutant strain. Consistent with this,
      real-time reverse transcription-PCR revealed a significant increase in def
      transcript titer. No mutations were found in the region upstream of def that
      might account for altered expression; however, pulsed-field gel electrophoresis
      suggested that a genetic rearrangement of the region containing def had occurred.
      Using a combination of PCR, sequencing, and Southern blot analyses, it was
      determined that the def gene had undergone copy number amplification, explaining
      the high level of target protein expression. Inactivation of the AcrAB-TolC
      efflux pump in this mutant increased susceptibility 16-fold, highlighting the
      role of efflux in exacerbating the overall reduced susceptibility resulting from
      target overexpression.

PMID- 17220414
TI  - Sequencing and analysis of the biosynthetic gene cluster of the lipopeptide
      antibiotic Friulimicin in Actinoplanes friuliensis.
AB  - Actinoplanes friuliensis produces the lipopeptide antibiotic friulimicin, which
      is a cyclic peptide with one exocyclic amino acid linked to a branched-chain
      fatty acid acyl residue. The structural relationship to daptomycin and the
      excellent antibacterial performance of friulimicin make the antibiotic an
      attractive drug candidate. The complete friulimicin biosynthetic gene cluster of
      24 open reading frames from A. friuliensis was sequenced and analyzed. In
      addition to genes for regulation, self-resistance, and transport, the cluster
      contains genes encoding peptide synthetases, proteins involved in the synthesis
      and linkage of the fatty acid component of the antibiotic, and proteins involved
      in the synthesis of the nonproteinogenic amino acids pipecolinic acid,
      methylaspartic acid, and 2,3-diaminobutyric acid. By using heterologous gene
      expression in Escherichia coli, we provide biochemical evidence for the
      stereoselective synthesis of L-pipecolinic acid by the deduced protein of the
      lysine cyclodeaminase gene pip. Furthermore, we show the involvement of the dabA
      and dabB genes in the biosynthesis of 2,3-diaminobutyric acid by gene
      inactivation and subsequent feeding experiments.

PMID- 17220415
TI  - Poly(D,L-lactide-coglycolide) particles containing gentamicin: pharmacokinetics
      and pharmacodynamics in Brucella melitensis-infected mice.
AB  - Drug delivery systems containing gentamicin were studied as a treatment against
      experimental brucellosis in mice. Micro- and nanoparticles prepared by using
      poly(D,L-lactide-coglycolide) (PLGA) 502H and microparticles made of PLGA 75:25H
      were successfully delivered to the liver and the spleen, the target organs for
      Brucella melitensis. Both polymers have the same molecular weight but have
      different lactic acid/glycolic acid ratios. Microparticles of PLGA 502H and
      75:25H released their contents in a sustained manner, in contrast to PLGA 502H
      nanoparticles, which were degraded almost completely during the first week
      postadministration. The values of the pharmacokinetic parameters after
      administration of a single intravenous dose of 1.5 mg/kg of body weight of loaded
      gentamicin revealed higher areas under the curve (AUCs) for the liver and the
      spleen and increased mean retention times (MRTs) compared to those for the free
      drug, indicating the successful uptake by phagocytic cells in both organs and the
      controlled release of the antibiotic. Both gentamicin-loaded PLGA 502H and 75:25H
      microparticles presented similar pharmacokinetic parameter values for the liver,
      but those made of PLGA 75:25 H were more effective in targeting the antibiotic to
      the spleen (higher AUCs and MRTs). The administration of three doses of 1.5 mg/kg
      significantly reduced the load associated with the splenic B. melitensis
      infection. Thus, the formulation made with the 75:25H polymer was more effective
      than that made with 502H microspheres (1.45-log and 0.45-log reductions,
      respectively, at 3 weeks posttreatment). Therefore, both, pharmacokinetic and
      pharmacodynamic parameters showed the suitability of 75:25H microspheres to
      reduce the infection of experimentally infected mice with B. melitensis.

PMID- 17220416
TI  - EthA, a common activator of thiocarbamide-containing drugs acting on different
      mycobacterial targets.
AB  - Many of the current antimycobacterial agents require some form of cellular
      activation unmasking reactive groups, which in turn will bind to their specific
      targets. Therefore, understanding the mechanisms of activation of current
      antimycobacterials not only helps to decipher mechanisms of drug resistance but
      may also facilitate the development of alternative activation strategies or of
      analogues that do not require such processes. Herein, through the use of
      genetically defined strains of Mycobacterium bovis BCG we provide evidence that
      EthA, previously shown to activate ethionamide, also converts isoxyl (ISO) and
      thiacetazone (TAC) into reactive species. These results were further supported by
      the development of an in vitro assay using purified recombinant EthA, which
      allowed direct assessment of the metabolism of ISO. Interestingly, biochemical
      analysis of [(14)C]acetate-labeled cultures suggested that all of these EthA
      activated drugs inhibit mycolic acid biosynthesis via different mechanisms
      through binding to specific targets. This report is also the first description of
      the molecular mechanism of action of TAC, a thiosemicarbazone antimicrobial agent
      that is still used in the treatment of tuberculosis as a second-line drug in many
      developing countries. Altogether, the results suggest that EthA is a common
      activator of thiocarbamide-containing drugs. The broad specificity of EthA can
      now be used to improve the activation process of these drugs, which may help
      overcome the toxicity problems associated with clinical thiocarbamide use.

PMID- 17220417
TI  - MexAB-OprM- and MexXY-overproducing mutants are very prevalent among clinical
      strains of Pseudomonas aeruginosa with reduced susceptibility to ticarcillin.

PMID- 17220418
TI  - In vitro activity of API-1252, a novel FabI inhibitor, against clinical isolates
      of Staphylococcus aureus and Staphylococcus epidermidis.

PMID- 17220419
TI  - In vitro studies with DQ-113 and comparison fluoroquinolones to determine
      propensities to select resistance in gram-positive cocci.
AB  - DQ-113 was compared in vitro to sitafloxacin, moxifloxacin, levofloxacin, and
      ciprofloxacin for potential to select mutational resistance in multiresistant
      staphylococci, pneumococci, and enterococci. Its ability to select less
      susceptible mutants varied according to species, being lowest with staphylococci,
      intermediate with pneumococci, and greatest with enterococci.

PMID- 17220420
TI  - Daptomycin susceptibility of unusual gram-positive bacteria: comparison of
      results obtained by the Etest and the broth microdilution method.
AB  - MICs of daptomycin, linezolid, and vancomycin against 212 isolates, including
      Listeria monocytogenes and Pediococcus, Leuconostoc, Rhodococcus, and Nocardia
      spp., were determined by the broth microdilution method; daptomycin MICs were
      also determined by the Etest. Except with those for Leuconostoc spp., daptomycin
      Etest MICs showed >90% agreement with MICs obtained by the broth microdilution
      method.

PMID- 17220421
TI  - In vitro activity of aurein 1.2 alone and in combination with antibiotics against
      gram-positive nosocomial cocci.
AB  - This study was performed to evaluate the in vitro activity of the amphibian
      peptide aurein 1.2 and to investigate its interaction with six antibiotics
      against nosocomial gram-positive cocci. All isolates were inhibited at
      concentrations of 1 to 16 mg/liter. Synergy was demonstrated when aurein 1.2 was
      combined with clarithromycin and minocycline.

PMID- 17220422
TI  - Genetics and expression of the carbapenem-hydrolyzing oxacillinase gene blaOXA-23
      in Acinetobacter baumannii.
AB  - The genetic structures surrounding the plasmid-carried blaOXA-23 oxacillinase
      gene, encoding resistance to carbapenems, were studied in Acinetobacter
      baumannii. ISAba1 and the novel element ISAba4 were detected upstream of the
      blaOXA-23 gene, providing promoter sequences for its expression. These insertion
      elements were likely involved in transposition processes at the origin of
      acquisition of this beta-lactamase gene.

PMID- 17220423
TI  - Universal in vitro antifungal resistance of genetic clades of the Fusarium solani
      species complex.
AB  - Eleven antifungal drugs were tested against representative isolates of the four
      phylogenetic clades of the Fusarium solani species complex obtained in a
      multilocus sequence analysis. They all showed very poor activity, with no
      differences among the clades. Amphotericin B was the most active drug.

PMID- 17220424
TI  - Comparison of a SYBR green I-based assay with a histidine-rich protein II enzyme
      linked immunosorbent assay for in vitro antimalarial drug efficacy testing and
      application to clinical isolates.
AB  - In vitro drug susceptibility testing with the malaria parasite has been used to
      assess the antimalarial activities of new compounds and to monitor drug
      resistance in field isolates. We investigated the validity of a SYBR green I
      fluorescent-based assay under various culture conditions and compared the assay
      results to those of previously published histidine-rich protein II (HRPII) enzyme
      linked immunosorbent assay (ELISA) methods. Reference strains of Plasmodium
      falciparum were cultured in vitro by using standard conditions in complete medium
      with and without phenol red before they were dispensed into 96-well plates
      predosed with chloroquine, mefloquine, or quinine. Following incubation, the
      culture supernatants were divided and the 50% inhibitory concentrations (IC50s)
      were determined by using a SYBR green I-based method and the HRPII capture ELISA
      method. There were no significant differences in IC50 values when phenol red was
      included in the medium. The IC50s and the IC90s of the antimalarials tested by
      both methods were similar or identical for each of the reference strains. Fresh
      clinical isolates of P. falciparum collected from imported cases of malaria in
      Lyon, France, were tested for in vitro resistance to chloroquine and mefloquine
      by using the validated SYBR green I and HRPII ELISA methods. The SYBR green I
      based method was able to calculate IC50 and IC90 values similar or identical to
      those calculated by the HRPII assay with fresh clinical samples without removal
      of white blood cells. The SYBR green I-based method for determination of drug
      sensitivity levels produced results comparable to those produced by other
      methods, showing that this method can be used routinely to conduct surveillance
      for drug resistance in P. falciparum with fresh or cultured parasites.

PMID- 17220425
TI  - First report of plasmid-mediated qnrA1 in a ciprofloxacin-resistant Escherichia
      coli strain in Latin America.
AB  - Among 144 ciprofloxacin-resistant Escherichia coli isolated in Brazil, one
      (0.69%) QnrA1-producing isolate was detected. The qnrA1 gene was associated with
      ISCR1. The QnrA1 determinant was carried on a 41-kb conjugative plasmid, which
      also carried a FOX-type cephalosporinase encoding gene and a class 1 integron
      with the aadB and catB3 cassettes. This is the first report of a qnrA-carrying
      isolate in a Latin American country.

PMID- 17220426
TI  - Heterologous production of albicidin: a promising approach to overproducing and
      characterizing this potent inhibitor of DNA gyrase.
AB  - The phytotoxin and polyketide antibiotic albicidin produced by Xanthomonas
      albilineans is a highly potent DNA gyrase inhibitor. Low yields of albicidin
      production have slowed studies of its chemical structure. Heterologous expression
      of albicidin biosynthetic genes in X. axonopodis pv. vesicatoria resulted in a
      sixfold increase in albicidin production, offering promising strategies for
      engineering overproduction.

PMID- 17220427
TI  - Thienorphine: receptor binding and behavioral effects in rhesus monkeys.
AB  - Thienorphine is an oripavine with long-lasting antinociceptive effects in mice
      that are thought to be mediated by mu-opioid receptors. This study examined the
      receptor binding of thienorphine in cell membrane homogenates and its behavioral
      effects in rhesus monkeys (Macaca mulatta). Affinity and potency were determined
      using radioligand displacement and stimulation of guanosine 5'-O-(3
      [35S]thio)triphosphate binding in C6 (mu, delta) and Chinese hamster ovary
      (kappa) cell membranes. Thienorphine displayed high affinity for kappa-, mu-, and
      delta-opioid receptors with K(i) values of 0.14, 0.22, and 0.69 nM, respectively.
      Thienorphine partially stimulated kappa-opioid (75%) and mu-opioid (19%)
      receptors and not delta-opioid receptors. Thienorphine dose-dependently increased
      tail-withdrawal latency for 50 degrees C water and not 55 degrees C water with
      effects lasting for more than 7 days. The kappa-opioid receptor antagonist nor
      binaltorphimine (nor-BNI) (3.2 mg/kg) and a large dose (1.0 mg/kg) of naltrexone
      prevented thienorphine-induced antinociception. Thienorphine enhanced the
      antinociceptive effects of morphine and U50,488 [trans-3, 4-dichloro-N-methyl-N
      [2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide] with 50 degrees C water; with
      55 degrees C water, thienorphine enhanced the effects of morphine and attenuated
      the effects of U50,488. In other monkeys, thienorphine decreased responding in
      both components of a multiple schedule of food presentation and stimulus shock
      termination for up to 8 days; naltrexone and nor-BNI partially prevented these
      rate-decreasing effects. In morphine-treated monkeys discriminating naltrexone,
      thienorphine, and U50,488 neither substituted for nor modified the naltrexone
      discriminative stimulus. Thienorphine and U50,488 produced the same directly
      observable signs. These results show that thienorphine has long-lasting effects
      that seem to be mediated by low-efficacy agonism at kappa-opioid receptors, both
      in vitro and in vivo.

PMID- 17220428
TI  - Regulation of oxidant-induced intestinal permeability by metalloprotease
      dependent epidermal growth factor receptor signaling.
AB  - Inflammatory bowel disease (IBD) affects more than 1 million Americans with more
      than 30,000 new cases diagnosed each year. IBD increases patient morbidity and
      susceptibility to colorectal cancer, yet its etiology remains unknown. Current
      models identify two key determinants of IBD pathogenesis: hyperpermeability of
      the gut epithelial barrier to bacterial products and an abnormal immune response
      to these products. Two factors seem critical for hyperpermeability: oxidant
      induced stress and proinflammatory cytokines (e.g., tumor necrosis factor-alpha).
      The aim of this study was to investigate the role of oxidant stress-mediated
      transactivation of the epidermal growth factor receptor (EGFR) in intestinal
      hyperpermeability. This study used the Caco-2 human colonic epithelial cell in
      vitro model of intestinal epithelium. Cells were grown on inserts for
      permeability and signaling studies and glass coverslips for microscopy studies.
      show that oxidant-induced intestinal hyperpermeability can be blocked by specific
      inhibitors of the EGFR, tumor necrosis factor convertase (TACE) metalloprotease,
      transforming growth factor (TGF)-alpha, and mitogen-activated protein kinases,
      especially extracellular signal-regulated kinase 1/2. We also show that oxidant
      initiates these signaling events, in part by causing translocation of TACE to
      cell-cell contact zones. In this study, our data identify a novel mechanism for
      oxidant-induced intestinal hyperpermeability relevant to IBD. We propose a new
      intestinal permeability model in which oxidant transactivates EGFR signaling by
      activation of TACE and cleavage of precursor TGF-alpha. These data could have a
      significant effect on our view of IBD pathogenesis and provide new therapeutic
      targets for IBD treatment.

PMID- 17220429
TI  - Validation list no. 113. 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, or an electronic copy of
      the published paper, 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- 17220430
TI  - Notification that new names and new combinations have appeared in volume 56, part
      10, 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- 17220431
TI  - List of changes in taxonomic opinion no. 5. Notification of changes in taxonomic
      opinion previously published outside the IJSEM.
AB  - The Bacteriological Code deals with the nomenclature of prokaryotes. This may
      include existing names (the Approved Lists of Bacterial Names) as well as new
      names and new combinations. In this sense the Code is also dealing indirectly
      with taxonomic opinions. However, as with most codes of nomenclature there are no
      mechanisms for formally recording taxonomic opinions that do not involve the
      creation of new names or new combinations. In particular, it would be desirable
      for taxonomic opinions resulting from the creation of synonyms or emended
      descriptions to be made widely available to the public. In 2004, the Editorial
      Board of the International Journal of Systematic and Evolutionary Microbiology
      (IJSEM) agreed unanimously that it was desirable to cover such changes in
      taxonomic opinions (i.e. the creation of synonyms or the emendation of
      circumscriptions) previously published outside the IJSEM, and to introduce a List
      of Changes in Taxonomic Opinion [Notification of changes in taxonomic opinion
      previously published outside the IJSEM; Euzeby et al. (2004). Int J Syst Evol
      Microbiol 54, 1429-1430]. Scientists wishing to have changes in taxonomic opinion
      included in future lists should send one copy of the pertinent reprint or a
      photocopy or a PDF file thereof to the IJSEM Editorial Office or to the Lists
      Editor. It must be stressed that the date of proposed taxonomic changes is the
      date of the original publication not the date of publication of the list.
      Taxonomic opinions included in the List of Changes in Taxonomic Opinion cannot be
      considered as validly published nor, in any other way, approved by the
      International Committee on Systematics of Prokaryotes and its Judicial
      Commission. The names that are to be used are those that are the "correct names"
      (in the sense of Principle 6) in the opinion of the bacteriologist, with a given
      circumscription, position and rank. A particular name, circumscription, position
      and rank does not have to be adopted in all circumstances. Consequently, the List
      of Changes in Taxonomic Opinion must be considered as a service to bacteriology
      and it has no "official character", other than providing a centralized point for
      registering/indexing such changes in a way that makes them easily accessible to
      the scientific community.

PMID- 17220432
TI  - Paenibacillus sabinae sp. nov., a nitrogen-fixing species isolated from the
      rhizosphere soils of shrubs.
AB  - Five novel endospore-forming, nitrogen-fixing bacterial strains were isolated
      from the rhizosphere soils of plants of the species Sabina squamata, Weigela
      florida and Zanthoxylum simulans. A phylogenetic analysis based on 16S rRNA gene
      sequences revealed that the five strains formed a distinct cluster within the
      genus Paenibacillus. These novel strains showed the highest levels (96.2-98.2 %)
      of 16S rRNA gene sequence similarity with Paenibacillus azotofixans. However, the
      DNA-DNA relatedness between these novel strains and P. azotofixans was 12.9-29.5
      %. The DNA G+C contents of the five strains were found to be 51.9-52.9 mol%.
      Phenotypic analyses showed that a significant feature of the novel strains
      (differentiating them from P. azotofixans and other Paenibacillus species) is
      that all of them were unable to produce acid and gas from various carbohydrates
      such as glucose, sucrose, lactose and fructose. Anteiso-branched C(15 : 0) was
      the major fatty acid present in the novel type strain. On the basis of these
      data, the five novel strains represent a novel species of the genus
      Paenibacillus, for which the name Paenibacillus sabinae sp. nov. is proposed. The
      type strain is T27(T) (=CCBAU 10202(T)=DSM 17841(T)).

PMID- 17220433
TI  - Pseudoalteromonas marina sp. nov., a marine bacterium isolated from tidal flats
      of the Yellow Sea, and reclassification of Pseudoalteromonas sagamiensis as
      Algicola sagamiensis comb. nov.
AB  - Two Gram-negative, motile and strictly aerobic marine bacteria were isolated from
      a tidal flat sediment sample obtained from Dae-Chun, Chung-Nam, Korea. They were
      preliminarily identified as Pseudoalteromonas-like bacteria, based on 16S rRNA
      gene sequence analysis showing nearly identical sequences (>99.7 % sequence
      similarity) and the highest similarity (98.4 %) to the species Pseudoalteromonas
      undina. Some phenotypic features of the newly isolated strains were similar to
      those of members of the genus Pseudoalteromonas, but several physiological and
      chemo-taxonomical properties readily distinguished the new isolates from
      previously described species. DNA-DNA hybridization with type strains of
      phylogenetically closely related species demonstrated that the isolates represent
      a novel Pseudoalteromonas species, for which the name Pseudoalteromonas marina
      sp. nov. is proposed, with the type strain mano4(T) (=KCTC 12242(T)=DSM
      17587(T)). In addition, on the basis of this study and polyphasic data obtained
      from previous work, it is proposed that the species Pseudoalteromonas sagamiensis
      should be reclassified as Algicola sagamiensis comb. nov. and that strain B-10
      31(T) (=DSM 14643(T)=JCM 11461(T)) be designated the type strain.

PMID- 17220434
TI  - Haladaptatus paucihalophilus gen. nov., sp. nov., a halophilic archaeon isolated
      from a low-salt, sulfide-rich spring.
AB  - Two novel strains of halophilic archaea, DX253(T) and GY252, were isolated from
      Zodletone Spring, a low-salt, sulfide- and sulfur-rich spring in south-western
      Oklahoma, USA. The cells were cocci or coccobacilli and occurred singly or in
      pairs. The two strains grew in a wide range of salt concentrations (0.8-5.1 M)
      and required at least 5 mM Mg(2+) for growth. The pH range for growth was 5-7.5
      and the temperature range was 25-45 degrees C. In addition to having the capacity
      to grow at relatively low salt concentrations, cells remained viable in distilled
      water after prolonged incubation. The two diether phospholipids that are typical
      of members of the order Halobacteriales, phosphatidylglycerol and
      phosphatidylglycerol phosphate methyl ester, were present. Phosphatidylglycerol
      sulfate and two unidentified glycolipids were also detected. Each strain had two
      distinct 16S rRNA gene sequences that were only 89.5-90.8 % similar to sequences
      from the most closely related cultured and recognized species within the order
      Halobacteriales. The DNA G+C content of the type strain was found to be 60.5
      mol%. The closest relatives were clones and uncharacterized isolates obtained
      from coastal salt-marsh sediments with salinities equivalent to that of seawater.
      The physiological, biochemical and phylogenetic differences between strains
      DX253(T) and GY252 and other previously described genera of extremely halophilic
      archaea suggest that these novel strains represent a novel species and genus
      within the family Halobacteriaceae, for which the name Haladaptatus
      paucihalophilus gen. nov., sp. nov. is proposed. The type strain is DX253(T)
      (=JCM 13897(T)=DSM 18195(T)=ATCC BAA-1313(T)=KCTC 4006(T)).

PMID- 17220435
TI  - dnaJ gene sequence-based assay for species identification and phylogenetic
      grouping in the genus Staphylococcus.
AB  - In the last few years, many attempts have been made to use conserved gene
      sequences for identification and for phylogenetic studies of Staphylococcus
      species. In an effort to identify a more reliable approach, a dnaJ gene sequence
      based database was created. In this study, an approximately 883 bp portion of the
      dnaJ gene sequence from 45 staphylococcal type strains was compared with 16S rRNA
      and other conserved gene (hsp60, sodA and rpoB) sequences available in public
      databases. Nucleotide sequence comparisons revealed that the staphylococcal dnaJ
      gene showed higher discrimination (mean similarity 77.6 %) than the 16S rRNA
      (mean similarity 97.4 %), rpoB (mean similarity 86 %), hsp60 (mean similarity 82
      %) and sodA (mean similarity 81.5 %) genes. Analysis of the dnaJ gene sequence
      from 20 Staphylococcus isolates representing two clinically important species
      showed <1 % sequence divergence. Phylogenetic data obtained from the dnaJ gene
      sequence were in general agreement with those of 16S rRNA gene sequence analysis
      and DNA-DNA reassociation studies. In conclusion, the dnaJ gene sequence-based
      assay is an effective alternative to currently used methods, including 16S rRNA
      gene sequencing, for identification and taxonomical analysis of Staphylococcus
      species.

PMID- 17220436
TI  - Simplicispira limi sp. nov., isolated from activated sludge.
AB  - A Gram-negative, motile, rod-shaped bacterium, designated strain EMB325(T), was
      isolated from activated sludge that performed enhanced biological phosphorus
      removal in a sequencing batch reactor. The predominant fatty acids of strain
      EMB325(T) were summed feature 3 (C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH),
      C(16 : 0), C(18 : 1)omega7c and C(18 : 1)omega7c 11-methyl. The strain contained
      phosphatidylethanolamine and diphosphatidylglycerol as polar lipids. The G+C
      content of the genomic DNA was 63.3 mol%. The major quinone was Q-8. Phylogenetic
      analysis of 16S rRNA gene sequences showed that strain EMB325(T) formed a
      phyletic lineage with members of the genus Simplicispira and was most closely
      related to Simplicispira psychrophila LMG 5408(T) and Simplicispira metamorpha
      DSM 1837(T) with similarities of 98.1 and 97.9 %, respectively. Levels of DNA-DNA
      relatedness between strain EMB325(T) and S. psychrophila LMG 5408(T) and S.
      metamorpha DSM 1837(T) were 28 and 23 %, respectively. On the basis of
      chemotaxonomic data and molecular characteristics, strain EMB325(T) is considered
      to represent a novel species within the genus Simplicispira, for which the name
      Simplicispira limi sp. nov. is proposed. The type strain is EMB325(T) (=KCTC
      12608(T)=DSM 17964(T)).

PMID- 17220437
TI  - Nocardioides furvisabuli sp. nov., isolated from black sand.
AB  - A Gram-positive, rod-shaped, yellow-pigmented actinomycete, designated strain SBS
      26(T), was isolated from a sample of black sand from Samyang Beach on Jeju Island
      (Republic of Korea) and was subjected to polyphasic characterization to unravel
      its taxonomic status. Phylogenetic analyses based on 16S rRNA gene sequences
      revealed that the organism belongs to the genus Nocardioides but forms a distinct
      branch at the base of a Nocardioides ganghwensis-Nocardioides oleivorans cluster.
      The 16S rRNA gene sequence of strain SBS-26(T) showed the highest levels of
      similarity to those of N. ganghwensis JC2055(T) (97.7 %) and N. oleivorans DSM
      16090(T) (97.6 %). The levels of 16S rRNA gene sequence similarity between strain
      SBS-26(T) and other members of the genera Nocardioides and Marmoricola were in
      the range 93.0-96.2 %. The following chemotaxonomic characteristics support the
      phylogenetic association of strain SBS-26(T) with members of the genus
      Nocardioides: ll-diaminopimelic acid as the principal diamino acid of the
      peptidoglycan, MK-8(H(4)) as the major menaquinone, iso-C(16 : 0) as the
      predominant fatty acid and a DNA G+C content of 69.1 mol%. The polar lipids
      contained phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and an
      unknown phospholipid. On the basis of the phenotypic, chemotaxonomic and
      phylogenetic data, strain SBS-26(T) represents a novel species of the genus
      Nocardioides, for which the name Nocardioides furvisabuli sp. nov. is proposed.
      The type strain is strain SBS-26(T) (=JCM 13813(T)=NRRL B-24465(T)).

PMID- 17220438
TI  - Petrotoga halophila sp. nov., a thermophilic, moderately halophilic, fermentative
      bacterium isolated from an offshore oil well in Congo.
AB  - A novel thermophilic, moderately halophilic, rod-shaped bacterium, strain MET
      B(T), with a sheath-like outer structure (toga) was isolated from an offshore oil
      producing well in Congo, West Africa. Strain MET-B(T) was a Gram-negative
      bacterium with the ability to reduce elemental sulfur, but not sulfate,
      thiosulfate or sulfite into sulfide. The optimum growth conditions were 60
      degrees C, pH 6.7-7.2 and 4-6 % NaCl. The DNA G+C content was 34.6 mol%. Strain
      MET-B(T) was phylogenetically related to members of the genus Petrotoga;
      Petrotoga miotherma, Petrotoga olearia and Petrotoga mexicana were the closest
      relatives, with type strains exhibiting more than 99 % identity in an analysis of
      small-subunit rRNA gene sequences. The values for DNA-DNA relatedness between the
      type strains of these three species and strain MET-B(T) were less than 42 %. As
      MET-B(T) was found to be genetically and physiologically different from other
      species of the genus Petrotoga, this strain is proposed as representing a novel
      species, for which the name Petrotoga halophila sp. nov. is proposed. The type
      strain is MET-B(T) (=DSM 16923(T)=CCUG 50214(T)).

PMID- 17220439
TI  - Actinomadura rudentiformis sp. nov., isolated from soil.
AB  - As part of an antibiotic-screening programme, the actinomycete strain HMC1(T) was
      isolated from soil collected from the banks of the Gamka River in the Swartberg
      Nature Reserve, Western Cape Province, South Africa. The isolate produced
      branching vegetative mycelia, which entwined to form rope-like structures. It
      exhibited antibiosis against Enterococcus faecium VanA (a vancomycin-resistant
      clinical strain) and Mycobacterium aurum A+. Organic solvent extracts of the
      culture filtrate and mycelial mass of strain HMC1(T) exhibited moderate
      antibiosis against Mycobacterium aurum A+, Mycobacterium bovis BCG (Tokyo) and
      Mycobacterium tuberculosis H37Rv(T). The chemotaxonomic characteristics of strain
      HMC1(T) corresponded with those of members of the genus Actinomadura.
      Furthermore, phylogenetic analysis based on the 16S rRNA gene showed that the
      strain was closely related to members of the genus Actinomadura. Phenotypic and
      16S rRNA gene sequence analyses indicated that strain HMC1(T) represents a novel
      species of the genus Actinomadura, for which the name Actinomadura rudentiformis
      sp. nov. is proposed. The type strain is HMC1(T) (=DSM 44962(T)=NRRL B-24458(T)).

PMID- 17220440
TI  - Terribacillus saccharophilus gen. nov., sp. nov. and Terribacillus halophilus sp.
      nov., spore-forming bacteria isolated from field soil in Japan.
AB  - Three strains, 002-048(T), RB589 and 002-051(T), isolated from field soil in
      Japan, were characterized using a polyphasic approach. The isolates were Gram
      positive, strictly aerobic, non-motile rods that formed ellipsoidal, subterminal
      endospores. The chemotaxonomic characteristics of these isolates included the
      presence of meso-diaminopimelic acid as the cell-wall peptidoglycan, anteiso-C(15
      : 0) and anteiso-C(17 : 0) as the major cellular fatty acids and MK-7 as the
      predominant menaquinone. The DNA G+C content was 44-46 mol%. Phylogenetic
      analyses based on 16S rRNA gene sequences revealed that the isolates represented
      an independent lineage that is distinct from related taxa and exhibited less than
      94.3 % sequence similarity with respect to those taxa. Moreover, a DNA-DNA
      hybridization analysis showed that the three isolates represented two species. On
      the basis of their phenotypic and phylogenetic distinctiveness, the isolates
      represent two species within a novel genus, for which the names Terribacillus
      saccharophilus gen. nov., sp. nov. and Terribacillus halophilus sp. nov. are
      proposed. The type strain of T. saccharophilus is 002-048(T) (=IAM 15309(T)=KCTC
      13936(T)) and the type strain of T. halophilus is 002-051(T) (=IAM 15310(T)=KCTC
      13937(T)).

PMID- 17220441
TI  - Humicoccus flavidus gen. nov., sp. nov., isolated from soil.
AB  - A Gram-positive, non-motile, spherical, non-spore-forming bacterial strain, DS
      52(T), was isolated from soil from Dokdo, Korea, and its taxonomic position was
      investigated by using a polyphasic approach. It grew optimally at 25 degrees C
      and pH 6.0-7.0. Strain DS-52(T) had meso-diaminopimelic acid as the diagnostic
      diamino acid in the cell-wall peptidoglycan, and galactose, mannose, xylose and
      rhamnose as whole-cell sugars. It contained MK-8(H(4)) and MK-9(H(4)) as the
      predominant menaquinones and anteiso-C(15 : 0), iso-C(15 : 0) and C(17 : 0) as
      major fatty acids. Major polar lipids were diphosphatidylglycerol,
      phosphatidylethanolamine and phosphatidyldimethylethanolamine. Phylogenetic
      analyses based on 16S rRNA gene sequences showed that strain DS-52(T) is most
      closely related to the genus Nakamurella of the suborder Frankineae. Strain DS
      52(T) exhibited 16S rRNA gene sequence similarity values of 96.5 % to Nakamurella
      multipartita JCM 9543(T) and 92.0-93.9 % to other members of the suborder
      Frankineae. The diagnostic diamino acid type and polar lipid profile of strain DS
      52(T) were the same as those of the genus Nakamurella. However, strain DS-52(T)
      could be clearly distinguished from the genus Nakamurella by differences in
      predominant menaquinones, major fatty acids and cell-wall sugars. Accordingly,
      based on combined phenotypic, chemotaxonomic and phylogenetic data, strain DS
      52(T) (=KCTC 19127(T)=CIP 108919(T)) is proposed as the type strain of a novel
      species in a new genus, Humicoccus flavidus gen. nov., sp. nov.

PMID- 17220442
TI  - Shewanella psychrophila sp. nov. and Shewanella piezotolerans sp. nov., isolated
      from west Pacific deep-sea sediment.
AB  - Two Shewanella-like bacterial strains, WP2(T) and WP3(T), which were isolated
      from west Pacific deep-sea sediment, were studied to determine their taxonomic
      position. Cells of the two bacteria were facultatively anaerobic, Gram-negative
      rods and motile by means of a single polar flagellum. Strain WP2(T) was
      psychrophilic, growing optimally at about 10-15 degrees C, whereas strain WP3(T)
      was psychrotolerant, growing optimally at 15-20 degrees C. The two strains grew
      in the pressure range 0.1-50 MPa, with optimal growth at 20 MPa. Strain WP3(T)
      was able to use nitrate, fumarate, trimethylamine N-oxide (TMAO), DMSO and
      insoluble Fe(III) as terminal electron acceptors during anaerobic growth, whereas
      strain WP2(T) was able to use only nitrate, TMAO and DMSO. The 16S rRNA gene
      sequences of strains WP2(T) and WP3(T) were 97 % identical, and showed highest
      similarity (97 %) to those of Shewanella fidelis KMM 3589 and Shewanella benthica
      ATCC 43992(T), respectively. The gyrB gene sequences of strains WP2(T)and WP3 (T)
      were also determined, and showed highest similarity to those of Shewanella
      violacea JCM 10179(T) (90 %) and Shewanella sairae SM2-1(T) (87 %), respectively.
      Contrary to the 16S rRNA gene sequence results, the phylogeny based on gyrB gene
      sequence analysis placed strain WP2(T), S. violacea and S. benthica in one group,
      while strain WP3(T) grouped with S. fidelis and S. sairae. DNA-DNA hybridization
      experiments supported the placement of strain WP2(T) with S. violacea and S.
      benthica. Phylogenetic evidence, together with DNA-DNA relatedness and phenotypic
      characteristics, indicated that the two new strains represented two novel deep
      sea Shewanella species. The names Shewanella psychrophila sp. nov. (type strain
      WP2(T)=JCM 13876(T)=CGMCC 1.6159(T)) and Shewanella piezotolerans (type strain
      WP3(T)=JCM 13877(T)=CGMCC 1.6160(T)) are proposed.

PMID- 17220443
TI  - Micrococcus flavus sp. nov., isolated from activated sludge in a bioreactor.
AB  - Bacterial strain LW4(T) was isolated from activated sludge of a wastewater
      treatment bioreactor. Cells of strain LW4(T) were Gram-positive cocci, with a
      diameter of 0.7-1.0 microm. Colonies produced on LB agar plates were yellow,
      smooth, circular and 0.5-1.5 mm in diameter. Strain LW4(T) was aerobic and grew
      over the temperature range 26-34 degrees C and pH range 5-9, with optimal growth
      at 30.5-31.5 degrees C and pH 6.0-6.2. The cell-wall peptidoglycan of strain
      LW4(T) contained amino acid residues of lysine, glutamic acid, alanine, glycine
      and aspartic acid. The most abundant cellular fatty acids of strain LW4(T) were
      anteiso-C(15 : 0) (32.15 %) and iso-C(15 : 0) (31.65 %). Major respiratory
      quinones were MK-8(H(2)) (57.3 %) and MK-7(H(2)) (32.9 %). The DNA G+C content
      was 71.4 mol% (T(m)). 16S rRNA gene sequence analysis indicated that strain
      LW4(T) was phylogenetically related to members of the genus Micrococcus, with
      similarities ranging from 96.5 to 97.3 %. Levels of DNA-DNA relatedness of strain
      LW4(T) to Micrococcus luteus DSM 20030(T), Micrococcus lylae DSM 20315(T) and
      Micrococcus antarcticus AS 1.2372(T) were 55, 48 and 36 %, respectively. Based on
      these results, it is concluded that strain LW4(T) represents a novel species of
      the genus Micrococcus, for which the name Micrococcus flavus sp. nov. is
      proposed. The type strain is strain LW4(T) (=CGMCC 1.5361(T)=JCM 14000(T)).

PMID- 17220444
TI  - Paenibacillus terrigena sp. nov., isolated from soil.
AB  - A novel Gram-positive bacterium, strain A35(T), was isolated from coastal soil at
      Chiba, Japan, and was identified as a member of the genus Paenibacillus on the
      basis of phenotypic and phylogenetic analyses. The bacterium was found to be a
      facultatively anaerobic and endospore-forming rod. The predominant menaquinone
      was MK-7, the major cellular fatty acid was anteiso-C(15 : 0) and the DNA G+C
      content was 48.1 mol%. The levels of 16S rRNA gene sequence similarity between
      strain A35(T) and Paenibacillus species with validly published names were less
      than 94 %. Strain A35(T) was clearly distinguishable from reference species for
      the genus Paenibacillus. Therefore, on the basis of these data, a novel species
      of the genus Paenibacillus, Paenibacillus terrigena sp. nov., is proposed. The
      type strain is A35(T) (=IAM 15291(T)=CCTCC AB206026(T)).

PMID- 17220445
TI  - Donghicola eburneus gen. nov., sp. nov., isolated from seawater of the East Sea
      in Korea.
AB  - A Gram-negative, aerobic, slightly halophilic, non-motile and coccoid- or rod
      shaped bacterial strain, SW-277(T), was isolated from seawater, Korea, and
      subjected to a polyphasic taxonomic study. Strain SW-277(T) was catalase- and
      oxidase-positive and grew optimally at pH 7.0-8.0 and 37 degrees C in the
      presence of 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene
      sequences showed that strain SW-277(T) belongs to the Alphaproteobacteria as part
      of the clade comprising the genera Roseivivax and Salipiger with a bootstrap
      resampling value of 72.5 %. 16S rRNA gene sequence similarity values between
      strain SW-277(T) and members of the genera Roseivivax and Salipiger were between
      93.8 and 94.7 %. Strain SW-277(T) contained Q-10 as the predominant ubiquinone
      and C(18 : 1)omega7c and C(16 : 0) as the major fatty acids. The DNA G+C content
      was 59.7 mol%. Strain SW-277(T) could be distinguished from members of the
      phylogenetically related genera Salipiger and Roseivivax by phenotypic
      differences and low 16S rRNA gene similarity values. On the basis of phenotypic,
      chemotaxonomic, genotypic and phylogenetic data, strain SW-277(T) (=KCTC
      12735(T)=JCM 13604(T)) should be classified as a representative of a novel
      species in a new genus, Donghicola eburneus gen. nov., sp. nov.

PMID- 17220446
TI  - Marinobacterium halophilum sp. nov., a marine bacterium isolated from the Yellow
      Sea.
AB  - A moderately halophilic, aerobic, Gram-negative bacterium was isolated from a
      tidal flat area of Dae-Chun, Chung-Nam, Korea. The strain, designated mano11(T),
      comprised rod-shaped cells that were motile by means of polar flagella. It grew
      with 3-12 % NaCl and at 4-37 degrees C and pH 5.3-9.3. The predominant
      menaquinone present in this strain was Q-8 [corrected] and diaminopimelic acid
      was not found in the cell-wall peptidoglycan. A phylogenetic analysis based on
      16S rRNA gene sequences showed that strain mano11(T) belongs to the genus
      Marinobacterium. Strain mano11(T) exhibited 92.8-98.3 % 16S rRNA gene sequence
      similarity when compared with the type strains of three other species of the
      genus Marinobacterium. DNA-DNA hybridization between strain mano11(T) and
      Marinobacterium georgiense DSM 11526(T), its closest relative in terms of 16S
      rRNA gene sequence similarity, was 13 %. On the basis of the phenotypic, genetic
      and phylogenetic data, strain mano11(T) represents a novel species of the genus
      Marinobacterium, for which the name Marinobacterium halophilum sp. nov. is
      proposed. The type strain is mano11(T) (=KCTC 12240(T)=DSM 17586(T)).

PMID- 17220447
TI  - DNA-DNA hybridization values and their relationship to whole-genome sequence
      similarities.
AB  - DNA-DNA hybridization (DDH) values have been used by bacterial taxonomists since
      the 1960s to determine relatedness between strains and are still the most
      important criterion in the delineation of bacterial species. Since the extent of
      hybridization between a pair of strains is ultimately governed by their
      respective genomic sequences, we examined the quantitative relationship between
      DDH values and genome sequence-derived parameters, such as the average nucleotide
      identity (ANI) of common genes and the percentage of conserved DNA. A total of
      124 DDH values were determined for 28 strains for which genome sequences were
      available. The strains belong to six important and diverse groups of bacteria for
      which the intra-group 16S rRNA gene sequence identity was greater than 94 %. The
      results revealed a close relationship between DDH values and ANI and between DNA
      DNA hybridization and the percentage of conserved DNA for each pair of strains.
      The recommended cut-off point of 70 % DDH for species delineation corresponded to
      95 % ANI and 69 % conserved DNA. When the analysis was restricted to the protein
      coding portion of the genome, 70 % DDH corresponded to 85 % conserved genes for a
      pair of strains. These results reveal extensive gene diversity within the current
      concept of "species". Examination of reciprocal values indicated that the level
      of experimental error associated with the DDH method is too high to reveal the
      subtle differences in genome size among the strains sampled. It is concluded that
      ANI can accurately replace DDH values for strains for which genome sequences are
      available.

PMID- 17220448
TI  - Agrococcus casei sp. nov., isolated from the surfaces of smear-ripened cheeses.
AB  - Seven Gram-positive, coryneform bacteria with virtually identical whole-organism
      protein patterns were isolated from the surface of smear-ripened cheeses.
      Representatives of these strains were the subject of a polyphasic study designed
      to establish their taxonomic status. The organisms formed a distinct branch in
      the Microbacteriaceae 16S rRNA gene tree and were most closely related to members
      of the genus Agrococcus, sharing sequence similarities of 95.4-98.7 %. The
      chemotaxonomic profiles of the strains were consistent with their classification
      in the genus Agrococcus. The combined genotypic and phenotypic data show that the
      isolates should be classified in the genus Agrococcus as representatives of a
      novel species. The name Agrococcus casei sp. nov. is proposed for this taxon.
      Isolate R-17892t2(T) (=DSM 18061(T)=LMG 22410(T)) is the type strain of
      Agrococcus casei sp. nov.

PMID- 17220449
TI  - Desulfovirgula thermocuniculi gen. nov., sp. nov., a thermophilic sulfate-reducer
      isolated from a geothermal underground mine in Japan.
AB  - A thermophilic, Gram-positive, endospore-forming, sulfate-reducing bacterial
      strain, designated RL80JIV(T), was isolated from a geothermally active
      underground mine in Japan. Cells were rod-shaped and motile. The temperature and
      pH ranges for growth were 61-80 degrees C (optimum at 69-72 degrees C) and pH 6.4
      7.9 (optimum at pH 6.8-7.3), and the strain tolerated up to 0.5 % NaCl. Strain
      RL80JIV(T) utilized sulfate, sulfite, thiosulfate and elemental sulfur as
      electron acceptors. Electron donors utilized were H(2) in the presence of CO(2),
      and carboxylic acids. Fermentative growth occurred on lactate and pyruvate. The
      cell wall contained meso-diaminopimelic acid and the major respiratory isoprenoid
      quinone was menaquinone MK-7. Major whole-cell fatty acids were iso-C(15 : 0),
      iso-C(17 : 0) and C(16 : 0). Strain RL80JIV(T) was found to be affiliated with
      the thiosulfate-reducer Thermanaeromonas toyohensis DSM 14490(T) (90.9 % 16S rRNA
      gene sequence similarity) and with the sulfate-reducer Desulfotomaculum
      thermocisternum DSM 10259(T) (90.0 % similarity). Strain RL80JIV(T) is therefore
      considered to represent a novel species of a new genus, for which the name
      Desulfovirgula thermocuniculi gen. nov., sp. nov. is proposed. The type strain of
      Desulfovirgula thermocuniculi is RL80JIV(T) (=DSM 16036(T)=JCM 13928(T)).

PMID- 17220450
TI  - Haloarcula amylolytica sp. nov., an extremely halophilic archaeon isolated from
      Aibi salt lake in Xin-Jiang, China.
AB  - A starch-hydrolysing and extremely halophilic archaeon (strain BD-3(T)), isolated
      from Aibi salt lake in Xin-Jiang, China, was characterized phenotypically and
      genotypically in order to determine its taxonomic status. On the basis of its
      polar lipid composition, nucleotide sequences of its 16S rRNA genes, genomic DNA
      G+C content (62.4 mol%) and growth characteristics, the organism could be
      assigned to the genus Haloarcula. Phenotypic differences and low DNA-DNA
      hybridization values to related Haloarcula species distinguished strain BD-3(T)
      from recognized Haloarcula species. It is therefore concluded that strain BD-3(T)
      represents a novel species, for which the name Haloarcula amylolytica sp. nov. is
      proposed. The type strain is BD-3(T) (=CGMCC 1.5335(T)=JCM 13557(T)).

PMID- 17220451
TI  - Description of Sphingosinicella xenopeptidilytica sp. nov., a beta-peptide
      degrading species, and emended descriptions of the genus Sphingosinicella and the
      species Sphingosinicella microcystinivorans.
AB  - A Gram-negative, rod-shaped bacterium, strain 3-2W4(T), was isolated from the
      aeration tank of a wastewater treatment plant in Zurich and was found to have the
      exceptional capacity to degrade synthetic beta-peptides. 16S rRNA gene sequence
      analysis showed that strain 3-2W4(T) is closely related to Sphingosinicella
      microcystinivorans Y2(T), but DNA-DNA hybridization experiments between these two
      strains revealed that they belong to two different species. The two strains
      displayed different fingerprints after PCR analysis using the repetitive primers
      BOX, ERIC and REP. Strain 3-2W4(T) did not degrade microcystin, which is a
      characteristic trait of Sphingosinicella microcystinivorans Y2(T). Like
      Sphingosinicella microcystinivorans Y2(T), strain 3-2W4(T) had the following
      characteristics: fatty acids comprising mainly C(18 : 1)omega7c, summed feature 3
      (C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH) and C(16 : 0), the presence of
      ubiquinone Q-10 and sym-homospermidine as the predominant polyamine compound. The
      polar lipid profiles of the two strains were almost identical, consisting of
      phosphatidylethanolamine, phosphatidylmonomethylethanolamine,
      phosphatidylglycerol and sphingoglycolipid. Strain 3-2W4(T) and Sphingosinicella
      microcystinivorans Y2(T) utilized the beta-peptides H-betahVal-betahAla-betahLeu
      OH and H-betahAla-betahLeu-OH as sole carbon and energy sources and shared beta
      peptidyl aminopeptidase activity in common, which distinguishes them from
      Sphingomonas and Sphingopyxis type strains. On the basis of these results, strain
      3-2W4(T) represents a novel species of the genus Sphingosinicella, for which the
      name Sphingosinicella xenopeptidilytica sp. nov. is proposed. The type strain is
      3-2W4(T) (=DSM 17130(T)=CCUG 52537(T)). The descriptions of the genus
      Sphingosinicella and the species Sphingosinicella microcystinivorans are emended.

PMID- 17220452
TI  - Sneathiella chinensis gen. nov., sp. nov., a novel marine alphaproteobacterium
      isolated from coastal sediment in Qingdao, China.
AB  - The taxonomic position of strain LMG 23452(T), which was isolated from coastal
      sediment from an aquaculture site near Qingdao, China, in 2000, was determined.
      Strain LMG 23452(T) comprised Gram-negative, non-spore-forming, motile rods and
      was found to be a halotolerant, aerobic, chemoheterotroph that produces catalase
      and oxidase. Comparative 16S rRNA gene sequence analysis revealed that strain LMG
      23452(T) shared approximately 89 % sequence similarity with members of the genera
      Devosia, Hyphomonas, Ensifer and Chelatococcus, which belong to two different
      orders within the Alphaproteobacteria. Further phylogenetic analysis of the 16S
      rRNA gene sequence showed that strain LMG 23452(T) formed a separate branch
      within the order Rhizobiales, falling between the genera Devosia and Ensifer of
      the families Hyphomicrobiaceae and Rhizobiaceae, respectively. Strain LMG
      23452(T) could be differentiated from its closest phylogenetic neighbours on the
      basis of several phenotypic features, including hydrolysis of the substrates
      starch and casein and assimilation of the carbohydrates d-glucose, d-mannose,
      mannitol, maltose and l-arabinose, and chemotaxonomically by the presence of the
      fatty acids C(14 : 0) 3-OH, C(16 : 1)omega11c, C(16 : 1)omega5c and C(18 :
      1)omega5c. The major fatty acids detected in strain LMG 23452(T) were C(18 :
      1)omega7c, C(16 : 0), C(19 : 0) cyclo omega8c, C(16 : 1)omega7c and C(17 :
      1)omega6c and the G+C content of the genomic DNA was 57.1 mol%. Therefore, the
      polyphasic data support the placement of strain LMG 23452(T) within a novel genus
      and species, for which the name Sneathiella chinensis gen. nov., sp. nov. is
      proposed. The type strain is LMG 23452(T) (=CBMAI 737(T)).

PMID- 17220453
TI  - Burkholderia soli sp. nov., isolated from soil cultivated with Korean ginseng.
AB  - A polyphasic study was carried out to clarify the taxonomic position of a Gram
      negative bacterium isolated from soil cultivated with Korean ginseng in the
      Eumseong region of Korea. The novel strain, GP25-8(T), grew optimally at pH 6-7,
      28 degrees C and 0-1 % NaCl (w/v). The major fatty acids were C(18 : 1)omega7c,
      summed feature 3 (C(16 : 1)omega7c/C(15 : 0) iso 2-OH) and C(16 : 0) (together
      representing 71.2 % of the total). The 16S rRNA gene sequence similarities
      between strain GP25-8(T) and members of the genus Burkholderia ranged from 94.7
      to 97.4 %, indicating that this novel strain was phylogenetically related to
      members of that genus. The novel strain showed the highest sequence similarities
      to Burkholderia caryophylli ATCC 25418(T) (97.4 %) and Burkholderia phenazinium
      LMG 2247(T) (97.2 %); the levels of DNA-DNA hybridization with these strains were
      28 and 12 %, respectively. These results support the conclusion that strain GP25
      8(T) represents a novel species within the genus Burkholderia, for which the name
      Burkholderia soli sp. nov. is proposed. The type strain is GP25-8(T) (=KACC
      11589(T)=DSM 18235(T)).

PMID- 17220454
TI  - Geobacter pickeringii sp. nov., Geobacter argillaceus sp. nov. and Pelosinus
      fermentans gen. nov., sp. nov., isolated from subsurface kaolin lenses.
AB  - The goal of this project was to isolate representative Fe(III)-reducing bacteria
      from kaolin clays that may influence iron mineralogy in kaolin. Two novel
      dissimilatory Fe(III)-reducing bacteria, strains G12(T) and G13(T), were isolated
      from sedimentary kaolin strata in Georgia (USA). Cells of strains G12(T) and
      G13(T) were motile, non-spore-forming regular rods, 1-2 mum long and 0.6 mum in
      diameter. Cells had one lateral flagellum. Phylogenetic analyses using the 16S
      rRNA gene sequence of the novel strains demonstrated their affiliation to the
      genus Geobacter. Strain G12(T) was most closely related to Geobacter pelophilus
      (94.7 %) and Geobacter chapellei (94.1 %). Strain G13(T) was most closely related
      to Geobacter grbiciae (95.3 %) and Geobacter metallireducens (95.1 %). Based on
      phylogenetic analyses and phenotypic differences between the novel isolates and
      other closely related species of the genus Geobacter, the isolates are proposed
      as representing two novel species, Geobacter argillaceus sp. nov. (type strain
      G12(T)=ATCC BAA-1139(T)=JCM 12999(T)) and Geobacter pickeringii sp. nov. (type
      strain G13(T)=ATCC BAA-1140(T)=DSM 17153(T)=JCM 13000(T)). Another isolate,
      strain R7(T), was derived from a primary kaolin deposit in Russia. The cells of
      strain R7(T) were motile, spore-forming, slightly curved rods, 0.6 x 2.0-6.0
      microm in size and with up to six peritrichous flagella. Strain R7(T) was capable
      of reducing Fe(III) only in the presence of a fermentable substrate. 16S rRNA
      gene sequence analysis demonstrated that this isolate is unique, showing less
      than 92 % similarity to bacteria of the Sporomusa-Pectinatus-Selenomomas phyletic
      group, including 'Anaerospora hongkongensis' (90.2 %), Acetonema longum (90.6 %),
      Dendrosporobacter quercicolus (90.9 %) and Anaerosinus glycerini (91.5 %). On the
      basis of phylogenetic analysis and physiological tests, strain R7(T) is proposed
      to represent a novel genus and species, Pelosinus fermentans gen. nov., sp. nov.
      (type strain R7(T)=DSM 17108(T)=ATCC BAA-1133(T)), in the Sporomusa-Pectinatus
      Selenomonas group.

PMID- 17220455
TI  - Nocardioides insulae sp. nov., isolated from soil.
AB  - A Gram-positive, rod-shaped or coccoid bacterial strain, DS-51(T), was isolated
      from a soil in Dokdo, Korea, and its taxonomic position was investigated by using
      a polyphasic approach. Strain DS-51(T) grew optimally at pH 8.0 and 30 degrees C
      without NaCl. Phylogenetic analyses based on 16S rRNA gene sequences showed that
      strain DS-51(T) forms a distinct line of descent within the radiation enclosed by
      the genus Nocardioides. The chemotaxonomic properties of strain DS-51(T) were
      consistent with those of the genus Nocardioides: the cell-wall peptidoglycan type
      was based on ll-2,6-diaminopimelic acid, MK-8(H(4)) was the predominant
      menaquinone and iso-C(16 : 0) was the major fatty acid. The DNA G+C content was
      71.1 mol%. The 16S rRNA gene sequence of strain DS-51(T) had similarity levels of
      92.5-95.1 % with the sequences of the type strains of Nocardioides species.
      Strain DS-51(T) could be distinguished from other Nocardioides species by
      differences in some phenotypic characteristics. On the basis of the phenotypic,
      chemotaxonomic and phylogenetic data, strain DS-51(T) represents a novel species
      of the genus Nocardioides, for which the name Nocardioides insulae sp. nov. is
      proposed. The type strain is DS-51(T) (=KCTC 19180(T)=DSM 17944(T)).

PMID- 17220456
TI  - Chryseobacterium caeni sp. nov., isolated from bioreactor sludge.
AB  - A Gram-negative, non-spore-forming, yellow-pigmented bacterium, strain N4(T), was
      isolated from a nickel-complexed cyanide-degrading bioreactor and subjected to a
      polyphasic taxonomic study. Phylogenetic analyses based on 16S rRNA gene
      sequences showed that strain N4(T) is affiliated to the genus Chryseobacterium of
      the family Flavobacteriaceae. The levels of 16S rRNA gene sequence similarity
      between strain N4(T) and the type strains of all known Chryseobacterium species
      were 93.2-95.8 %, suggesting that strain N4(T) represents a novel species within
      the genus Chryseobacterium. The strain contained iso-C(15 : 0) and summed feature
      4 as the major fatty acids and menaquinone MK-6 as the predominant respiratory
      quinone. The G+C content of the genomic DNA was 38.2 mol%. On the basis of its
      phenotypic properties and phylogenetic distinctiveness, strain N4(T) represents a
      novel species of the genus Chryseobacterium, for which the name Chryseobacterium
      caeni sp. nov. is proposed. The type strain is N4(T) (=KCTC 12506(T)=CCBAU
      10201(T)=DSM 17710(T)).

PMID- 17220457
TI  - Paenibacillus soli sp. nov., a xylanolytic bacterium isolated from soil.
AB  - Two novel polysaccharide-degrading bacteria (strains DCY03(T) and DCY04) were
      isolated from a soil sample of a ginseng field in the Republic of Korea and were
      identified as representing members of the genus Paenibacillus on the basis of
      phenotypic characteristics and phylogenetic inference based on 16S rRNA gene
      sequences. Cells of the two isolates were Gram-positive, spore-forming, non
      motile, straight rods. Based on DNA-DNA relatedness data, the strains were
      considered to belong to the same species. The DNA G+C content ranged from 56.6 to
      57.0 mol%. The predominant cellular fatty acid was anteiso-C(15 : 0) (63.8-62.8
      %). Levels of 16S rRNA gene sequence similarity between the two novel isolates
      and the type strains of recognized Paenibacillus species were 91.4-96.5 %.
      Strains DCY03(T) and DCY04 could clearly be distinguished from phylogenetically
      closely related Paenibacillus species on the basis of DNA-DNA relatedness data
      and phenotypic characteristics. Therefore, on the basis of these data, the two
      isolates are considered to represent a novel species of the genus Paenibacillus,
      for which the name Paenibacillus soli sp. nov. is proposed. The type strain is
      DCY03(T) (=KCTC 13010(T)=LMG 23604(T)).

PMID- 17220458
TI  - Demequina aestuarii gen. nov., sp. nov., a novel actinomycete of the suborder
      Micrococcineae, and reclassification of Cellulomonas fermentans Bagnara et al.
      1985 as Actinotalea fermentans gen. nov., comb. nov.
AB  - An actinobacterial strain containing demethylmenaquinone DMK-9(H(4)) as the
      diagnostic isoprenoid quinone was isolated from a tidal flat sediment sample,
      from South Korea. Phylogenetic analyses based on 16S rRNA gene sequences showed
      that strain JC2054(T) represents a distinct phyletic line within the suborder
      Micrococcineae of the order Actinomycetales. The closest phylogenetic neighbour
      was Cellulomonas fermentans, with 94.7 % 16S rRNA gene sequence similarity. The
      novel isolate was strictly aerobic and slightly halophilic, with optimum growth
      occurring in 2-4 % (w/v) NaCl. Cells were non-motile, non-sporulating and rod
      shaped. The peptidoglycan type was of the A-type of cross-linkage. l-ornithine
      was the diamino acid and d-glutamate represented the N-terminus of the
      interpeptide bridge. The predominant fatty acids were anteiso-branched and
      straight-chain fatty acids. The major polar lipids were phosphatidylinositol,
      diphosphatidylglycerol and an unknown phospholipid. The menaquinone composition
      of C. fermentans was determined to be MK-10(H(4)), MK-9(H(4)) and MK-8(H(4)) in
      the ratio 56 : 2 : 1. On the basis of the polyphasic evidence presented in this
      study, it is proposed that strain JC2054(T) should be classified as representing
      a novel genus and species of the suborder Micrococcineae, with the name Demequina
      aestuarii gen. nov., sp. nov. The type strain is JC2054(T) (=IMSNU 14027(T)=KCTC
      9919(T)=JCM 12123(T)). In addition, it was clear from the phylogenetic analysis
      and chemotaxonomic data that C. fermentans does not belong to the genus
      Cellulomonas or any other recognized genera. Therefore, C. fermentans should be
      reclassified as representing a novel genus, for which the name Actinotalea
      fermentans gen. nov., comb. nov. is proposed, with strain DSM 3133(T) (=ATCC
      43279(T)=CFBP 4259(T)=CIP 103003(T)=NBRC 15517(T)=JCM 9966(T)=LMG 16154(T)) as
      the type strain.

PMID- 17220459
TI  - Oceanicola nanhaiensis sp. nov., isolated from sediments of the South China Sea.
AB  - A Gram-negative, non-motile, rod-shaped bacterium, strain SS011B1-20(T), was
      isolated from sediments of the South China Sea. Growth occurred at NaCl
      concentrations between 0 and 10 % and at temperatures between 10 and 37 degrees
      C. Strain SS011B1-20(T) contained Q-10 as the major respiratory quinone and C(18
      : 1)omega7c (81.2 %), C(16 : 0) (7.0 %) and C(18 : 1) methyl (4.3 %) as the
      predominant fatty acids. The G+C content of the genomic DNA was 64.7 mol%. A
      phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain
      SS011B1-20(T) belonged to a clade within the genus Oceanicola in the
      Alphaproteobacteria, the highest sequence similarities being found with respect
      to Oceanicola batsensis (96.3 %) and with Oceanicola granulosus (94.9 %). Strain
      SS011B1-20(T) could be clearly distinguished from other Oceanicola species on the
      basis of the genotypic, phenotypic and phylogenetic data. Thus, it is proposed
      that strain SS011B1-20(T) represents a novel species of the genus Oceanicola,
      with the name Oceanicola nanhaiensis sp. nov. The type strain is SS011B1-20(T)
      (=LMG 23508(T)=CGMCC 1.6293(T)).

PMID- 17220460
TI  - Metschnikowia cerradonensis sp. nov., a yeast species isolated from ephemeral
      flowers and their nitidulid beetles in Brazil.
AB  - A novel yeast species, Metschnikowia cerradonensis sp. nov., is described from 12
      strains isolated from flowers of Ipomoea carnea and from beetles of the genus
      Conotelus in the Cerrado ecosystem in the region of Jalapao, Tocantins State,
      Brazil. Analysis of the sequences of the rRNA gene cluster suggested that M.
      cerradonensis is closely related to Metschnikowia santaceciliae, Metschnikowia
      continentalis and an undescribed species represented by strain UWOPS 00-154.1.
      These species mate together but ascospores are very rarely formed, showing that
      they represent distinct biological species. M. cerradonensis is apparently
      endemic to the Cerrado ecosystem of the Jalapao area. The type strain of M.
      cerradonensis is UFMG 03-T67.1(T) (h(+)) (=CBS 10409(T)=NRRL Y-48067(T)) and the
      designated allotype is UFMG 03-T68.1 (h(-)) (=CBS 10410=NRRL Y-48068).

PMID- 17220461
TI  - Proposed minimal standards for the description of genera, species and subspecies
      of the Pasteurellaceae.
AB  - Principles and guidelines are presented to ensure a solid scientific standard of
      papers dealing with the taxonomy of taxa of Pasteurellaceae Pohl 1981. The
      classification of the Pasteurellaceae is in principle based on a polyphasic
      approach. DNA sequencing of certain genes is very important for defining the
      borders of a taxon. However, the characteristics that are common to all members
      of the taxon and which might be helpful for separating it from related taxa must
      also be identified. Descriptions have to be based on as many strains as possible
      (inclusion of at least five strains is highly desirable), representing different
      sources with respect to geography and ecology, to allow proper characterization
      both phenotypically and genotypically, to establish the extent of diversity of
      the cluster to be named. A genus must be monophyletic based on 16S rRNA gene
      sequence-based phylogenetic analysis. Only in very rare cases is it acceptable
      that monophyly can not be achieved by 16S rRNA gene sequence comparison.
      Recently, the monophyly of genera has been confirmed by sequence comparison of
      housekeeping genes. In principle, a new genus should be recognized by a distinct
      phenotype, and characters that separate the new genus from its neighbours should
      be given clearly. Due to the overall importance of accurate classification of
      species, at least two genotypic methods are needed to show coherence and for
      separation at the species level. The main criterion for the classification of a
      novel species is that it forms a monophyletic group based on 16S rRNA gene
      sequence-based phylogenetic analysis. However, some groups might also include
      closely related species. In these cases, more sensitive tools for genetic
      recognition of species should be applied, such as DNA-DNA hybridizations. The
      comparison of housekeeping gene sequences has recently been used for genotypic
      definition of species. In order to separate species, phenotypic characters must
      also be identified to recognize them, and at least two phenotypic differences
      from existing species should be identified if possible. We recommend the use of
      the subspecies category only for subgroups associated with disease or similar
      biological characteristics. At the subspecies level, the genotypic groups must
      always be nested within the boundaries of an existing species. Phenotypic
      cohesion must be documented at the subspecies level and separation between
      subspecies and related species must be fully documented, as well as association
      with particular disease and host. An overview of methods previously used to
      characterize isolates of the Pasteurellaceae has been given. Genotypic and
      phenotypic methods are separated in relation to tests for investigating diversity
      and cohesion and to separate taxa at the level of genus as well as species and
      subspecies.

PMID- 17220462
TI  - Proposal to replace the illegitimate genus name Schineria Toth et al. 2001 with
      the genus name Ignatzschineria gen. nov. and to replace the illegitimate
      combination Schineria larvae Toth et al. 2001 with Ignatzschineria larvae comb.
      nov.
AB  - The prokaryotic, generic name Schineria Toth et al. 2001 is illegitimate owing to
      the prior existence of the name Schineria for a genus within the Diptera
      [Principle 2, Rule 51b(4) of the Bacteriological Code (1990 Revision)].
      Therefore, a new genus name, Ignatzschineria gen. nov., is proposed for this
      taxon. As a result, a new combination is required for the type species,
      Ignatzschineria larvae comb. nov., to replace the illegitimate combination
      Schineria larvae Toth et al. 2001.

PMID- 17220463
TI  - A 368-base-pair cis-acting HWP1 promoter region, HCR, of Candida albicans confers
      hypha-specific gene regulation and binds architectural transcription factors Nhp6
      and Gcf1p.
AB  - To elucidate the molecular mechanisms controlling the expression of the hypha
      specific adhesin gene HWP1 of Candida albicans, its promoter was dissected and
      analyzed using a green fluorescent protein reporter gene. A 368-bp region, the
      HWP1 control region (HCR), was critical for activation under hypha-inducing
      conditions and conferred developmental regulation to a heterologous ENO1
      promoter. A more distal region of the promoter served to amplify the level of
      promoter activation. Using gel mobility shift assays, a 249-bp subregion of HCR,
      HCRa, was found to bind at least four proteins from crude extracts of yeasts and
      hyphae with differing binding patterns dependent on cell morphology. Four
      proteins with DNA binding activities were identified by using sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis after separation by anion-exchange and
      heparin-Sepharose chromatography. One protein with high similarity to Nhp6, an
      HMG1 family member in Saccharomyces cerevisiae, and another with weak similarity
      to an HMG-like condensation factor from Physarum polycephalum implicated changes
      in chromatin structure as a critical process in hypha-specific gene regulation.
      Proteins with strong homology to histones were also found. These studies are the
      first to identify proteins that bind to a DNA segment that confers developmental
      gene regulation in C. albicans and suggest a new model for hypha-specific gene
      regulation.

PMID- 17220464
TI  - Molecular cloning of apicoplast-targeted Plasmodium falciparum DNA gyrase genes:
      unique intrinsic ATPase activity and ATP-independent dimerization of PfGyrB
      subunit.
AB  - DNA gyrase, a typical type II topoisomerase that can introduce negative
      supercoils in DNA, is essential for replication and transcription in prokaryotes.
      The apicomplexan parasite Plasmodium falciparum contains the genes for both
      gyrase A and gyrase B in its genome. Due to the large sizes of both proteins and
      the unusual codon usage of the highly AT-rich P. falciparum gyrA (PfgyrA) and
      PfgyrB genes, it has so far been impossible to characterize these proteins, which
      could be excellent drug targets. Here, we report the cloning, expression, and
      functional characterization of full-length PfGyrB and functional domains of
      PfGyrA. Unlike Escherichia coli GyrB, PfGyrB shows strong intrinsic ATPase
      activity and follows a linear pattern of ATP hydrolysis characteristic of dimer
      formation in the absence of ATP analogues. These unique features have not been
      reported for any known gyrase so far. The PfgyrB gene complemented the E. coli
      gyrase temperature-sensitive strain, and, together with the N-terminal domain of
      PfGyrA, it showed typical DNA cleavage activity. Furthermore, PfGyrA contains a
      unique leucine heptad repeat that might be responsible for dimerization. These
      results confirm the presence of DNA gyrase in eukaryotes and confer great
      potential for drug development and organelle DNA replication in the deadliest
      human malarial parasite, P. falciparum.

PMID- 17220465
TI  - Use of bimolecular fluorescence complementation to study in vivo interactions
      between Cdc42p and Rdi1p of Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae Cdc42p functions as a GTPase molecular switch,
      activating multiple signaling pathways required to regulate cell cycle
      progression and the actin cytoskeleton. Regulatory proteins control its GTP
      binding and hydrolysis and its subcellular localization, ensuring that Cdc42p is
      appropriately activated and localized at sites of polarized growth during the
      cell cycle. One of these, the Rdi1p guanine nucleotide dissociation inhibitor,
      negatively regulates Cdc42p by extracting it from cellular membranes. In this
      study, the technique of bimolecular fluorescence complementation (BiFC) was used
      to study the dynamic in vivo interactions between Cdc42p and Rdi1p. The BiFC data
      indicated that Cdc42p and Rdi1p interacted in the cytoplasm and around the
      periphery of the cell at the plasma membrane and that this interaction was
      enhanced at sites of polarized cell growth during the cell cycle, i.e., incipient
      bud sites, tips and sides of small- and medium-sized buds, and the mother-bud
      neck region. In addition, a ring-like structure containing the Cdc42p-Rdi1p
      complex transiently appeared following release from G1-phase cell cycle arrest. A
      homology model of the Cdc42p-Rdi1p complex was used to introduce mutations that
      were predicted to affect complex formation. These mutations resulted in altered
      BiFC interactions, restricting the complex exclusively to either the plasma
      membrane or the cytoplasm. Data from these studies have facilitated the temporal
      and spatial modeling of Rdi1p-dependent extraction of Cdc42p from the plasma
      membrane during the cell cycle.

PMID- 17220466
TI  - De novo sphingolipid synthesis is essential for viability, but not for transport
      of glycosylphosphatidylinositol-anchored proteins, in African trypanosomes.
AB  - De novo sphingolipid synthesis is required for the exit of
      glycosylphosphatidylinositol (GPI)-anchored membrane proteins from the
      endoplasmic reticulum in yeast. Using a pharmacological approach, we test the
      generality of this phenomenon by analyzing the transport of GPI-anchored cargo in
      widely divergent eukaryotic systems represented by African trypanosomes and HeLa
      cells. Myriocin, which blocks the first step of sphingolipid synthesis (serine +
      palmitate --> 3-ketodihydrosphingosine), inhibited the growth of cultured
      bloodstream parasites, and growth was rescued with exogenous 3
      ketodihydrosphingosine. Myriocin also blocked metabolic incorporation of
      [3H]serine into base-resistant sphingolipids. Biochemical analyses indicate that
      the radiolabeled lipids are not sphingomyelin or inositol phosphorylceramide,
      suggesting that bloodstream trypanosomes synthesize novel sphingolipids.
      Inhibition of de novo sphingolipid synthesis with myriocin had no adverse effect
      on either general secretory trafficking or GPI-dependent trafficking in
      trypanosomes, and similar results were obtained with HeLa cells. A mild effect on
      endocytosis was seen for bloodstream trypanosomes after prolonged incubation with
      myriocin. These results indicate that de novo synthesis of sphingolipids is not a
      general requirement for secretory trafficking in eukaryotic cells. However, in
      contrast to the closely related kinetoplastid Leishmania major, de novo
      sphingolipid synthesis is essential for the viability of bloodstream-stage
      African trypanosomes.

PMID- 17220467
TI  - Cdc37p is required for stress-induced high-osmolarity glycerol and protein kinase
      C mitogen-activated protein kinase pathway functionality by interaction with
      Hog1p and Slt2p (Mpk1p).
AB  - The yeast Saccharomyces cerevisiae utilizes rapidly responding mitogen-activated
      protein kinase (MAPK) signaling cascades to adapt efficiently to a changing
      environment. Here we report that phosphorylation of Cdc37p, an Hsp90 cochaperone,
      by casein kinase 2 controls the functionality of two MAPK cascades in yeast.
      These pathways, the high-osmolarity glycerol (HOG) pathway and the cell integrity
      (protein kinase C) MAPK pathway, mediate adaptive responses to high osmotic and
      cell wall stresses, respectively. Mutation of the phosphorylation site Ser14 in
      Cdc37p renders cells sensitive to osmotic stress and cell wall perturbation by
      calcofluor white. We found that levels of the MAPKs Hog1p and Slt2p (Mpk1p) in
      cells are reduced in a cdc37-S14A mutant, and consequently downstream responses
      mediated by Hog1p and Slt2p are compromised. Furthermore, we present evidence
      that Hog1p and Slt2p both interact in a complex with Cdc37p in vivo, something
      that has not been reported previously. The interaction of Hsp90, Slt2p, and Hog1p
      with Cdc37p depends on the phosphorylation status of Cdc37p. In fact, our
      biochemical data show that the osmosensitive phenotype of the cdc37-S14A mutant
      is due to the loss of the interaction between Cdc37p, Hog1p, and Hsp90. Likewise,
      during cell wall stress, the interaction of Slt2p with Cdc37p and Hsp90 is
      crucial for Slt2p-dependent downstream responses, such as the activation of the
      transcription factor Rlm1p. Interestingly, phosphorylated Slt2p, but not
      phosphorylated Hog1p, has an increased affinity for Cdc37p. Together these
      observations suggest that Cdc37p acts as a regulator of MAPK signaling.

PMID- 17220468
TI  - Hypokalemia, cardiac failure, and reporting NXY-059 safety for acute stroke.
AB  - NXY-059, an alpha-phenyl-N-tert-butyl nitrone derivative, is a free radical
      trapping agent presently in late clinical trials as a potential neuroprotectant
      limiting reperfusion injury following acute stroke. Two recent trials suggest
      that NXY-059 causes hypokalemia and associated cardiac disturbances. With regard
      to the mechanism of such association, most investigators agree that potent
      trapping of free radicals leads to the 11 beta-hydroxysteroid dehydrogenase
      blockade in kidneys, diminishing renal hydrocortisone oxidation and increasing
      K(+) ion urine excretion. Importantly, potassium deficiency represents the major
      avoidable cause of the array of serious cardiac adverse reactions: QT
      prolongation, Torsades de pointes and other life-threatening arrhythmias, and
      higher risks for perioperative cardiopulmonary resuscitation and cardiac death.
      Because a prime target for NXY-059 use will likely be acute strokes in the
      emergency room environment, the potential combination of the drug with intensive
      therapy including fluid infusions, particularly with diuretics, might be
      especially harmful because of the synergic depletion of potassium, which might
      also jeopardize the fate of the novel nitrone neuroprotectant.

PMID- 17220469
TI  - A case and review of acromegaly-induced cardiomyopathy and the relationship
      between growth hormone and heart failure: cause or cure or neither or both?
AB  - Growth hormone plays an integral role in the development and maintenance of
      structure and function of the heart. Specific involvement of the heart in
      acromegaly is termed acromegalic cardiomyopathy, manifested as concentric left
      ventricular hypertrophy and diastolic dys-function. Left untreated, it ultimately
      progresses to systolic heart failure. Heart failure from acromegalic
      cardiomyopathy is one of the most common causes of death in acromegaly. Current
      treatment options include different approaches to lower elevated growth hormone
      levels with improvement in symptoms, exercise tolerance, and echocardiographic
      improvement in regression of left ventricular hypertrophy and indices of
      diastolic dysfunction. On the other hand, growth hormone is essential for cardiac
      growth and function and exerts beneficial and protective effects on the
      cardiovascular system. Its potential role as adjunctive therapy in the treatment
      of heart failure as derived from experimental studies and clinical trials is
      discussed.

PMID- 17220470
TI  - Evolving perspectives on clopidogrel in the treatment of ischemic stroke.
AB  - Antiplatelet therapy is indicated for the treatment of ischemic stroke or
      transient ischemic attack (TIA). Aspirin reduces subsequent occlusive vascular
      events, including recurrent stroke, by about 25%. In such patients, clopidogrel
      has been evaluated in an effort to further reduce risk. In the Management of
      Atherothrombosis with Clopidogrel in High-risk Patients trial, the combination of
      clopidogrel plus aspirin was compared with clopidogrel alone, and the Clopidogrel
      for High Atherothrombotic Risk and Ischemic Stabilization, Management, and
      Avoidance trial tested the addition of clopidogrel to aspirin. Combination
      therapy with aspirin plus clopidogrel provided no significant incremental benefit
      compared with aspirin or clopidogrel alone. In addition, combination therapy
      increased the risk of serious bleeding. On the basis of the current totality of
      evidence for long-term treatment of survivors of ischemic stroke or TIA,
      clopidogrel is an effective alternative for patients who are intolerant to
      aspirin.

PMID- 17220471
TI  - Ranolazine, an inhibitor of the late sodium channel current, reduces postischemic
      myocardial dysfunction in the rabbit.
AB  - Ranolazine is a selective inhibitor of the late sodium current relative to peak
      sodium channel current, and via this mechanism, it may decrease sodium-dependent
      intracellular calcium overload during ischemia and reperfusion. Ranolazine
      reduces the frequency of angina attacks, but there is little information on its
      effects on myocardial stunning after short-term ischemia. The objective of this
      study was to test the effects of ranolazine on left ventricular (LV) function and
      myocardial stunning after ischemia/reperfusion in rabbits. Myocardial stunning
      was induced in rabbits by 15 minutes of coronary artery occlusion (CAO) followed
      by 3 hours reperfusion. Ten minutes before CAO, rabbits were randomly assigned to
      vehicle (n = 15) or ranolazine (2 mg/kg bolus plus 60 microg/kg/min infusion, IV,
      n = 15). Myocardial stunning was assessed by LV 2-dimensional echocardiography
      using, as a marker of severity, ischemic free-wall fractional thickening (FWft;
      systolic wall thickness - diastolic wall thickness/diastolic wall thickness).
      Regional ejection fraction (EF) was also assessed. During CAO, FWft was depressed
      in both groups, indicating an ischemic insult (FWft was reduced from 0.62 +/-
      0.05 at baseline to 0.10 +/- 0.04 in vehicle and from 0.73 +/- 0.05 to 0.26 +/-
      0.07 in ranolazine, P < 0.05, ranolazine vs vehicle). After reperfusion,
      previously ischemic myocardium remained stunned; however, FWft recovered
      significantly better in ranolazine (0.51 +/- 0.05) than in vehicle (0.35 +/-
      0.04, P = .027). Baseline EF was 0.65 +/- 0.02 in the ranolazine and 0.68 +/-
      0.02 in vehicle (P = ns). During CAO, EF was reduced by 36% +/- 6% in vehicle
      versus only 20% +/- 6% in ranolazine (P < .05). At the end of reperfusion, EF
      remained depressed in both groups, but the reduction in the vehicle group (25% +/
      5%) was significantly worse than in ranolazine (9% +/- 4%, P = .017).
      Improvement in function was independent of necrosis (negligible) or differences
      in hemodynamics (no differences between groups). Ranolazine treatment reduced
      myocardial stunning following brief ischemia/reperfusion suggesting that
      inhibiting the late sodium channel current may be a novel approach to treating
      stunning independent of effects on hemodynamics.

PMID- 17220472
TI  - Effect of barnidipine on blood pressure and serum metabolic parameters in
      patients with essential hypertension: a pilot study.
AB  - The effect of barnidipine, a calcium channel blocker, on metabolic parameters is
      not well known. The authors conducted the present pilot study to evaluate the
      possible effects of barnidipine on parameters involved in atherogenesis,
      oxidative stress, and clotting activity. This open-label intervention study
      included 40 adult patients with essential hypertension who received barnidipine
      10 mg once daily. Barnidipine significantly reduced systolic and diastolic blood
      pressure as well as isoprostane levels, which represent a reliable marker of
      oxidative stress. In contrast, barnidipine had a neutral effect on lipid profile
      and apolipoprotein levels, did not influence glucose homeostasis, had no effect
      on renal function, and did not cause any changes in electrolyte levels. Moreover,
      barnidipine did not affect either the clotting/fibrinolytic status (evaluated by
      measurement of fibrinogen, total plasminogen activator inhibitor, tissue
      plasminogen activator, and a2 antiplasmin) or the enzymatic activity of the
      inflammatory/anti-inflammatory mediators lipoprotein-associated phospholipase A2
      and paraoxonase 1, respectively. Barnidipine should be mainly considered as an
      antihypertensive agent with neutral effects on most of the studied metabolic
      parameters in hypertensive patients. Any antioxidant effect of barnidipine needs
      further investigation.

PMID- 17220473
TI  - Effect of atorvastatin on type 2 diabetic dyslipidemia.
AB  - Hyperlipidemia is commonly observed in patients with type 2 diabetes and is an
      independent risk factor for cardiovascular disease. The authors tested the effect
      of atorvastatin (10 mg/d) on 110 hyperlipidemic type 2 diabetes patients with low
      density lipoprotein cholesterol (LDL-C) levels exceeding 130 mg/d. The primary
      efficacy end point was the percentage change in LDL-C and high-density
      lipoprotein cholesterol (HDL-C), and secondary efficacy included the percentage
      change in apolipoproteins at weeks 6, 12, and 24. The tertiary goal was
      percentage change in free radical scavenger enzymes and oxidative stress. LDL-C
      was reduced by 25%, 39.3%, and 49.2%. A similar trend was observed in total
      cholesterol, triglyceride, non-HDL-C, and apolipoprotein (apo) B-100. HDL-C was
      raised by 3.2%, 6%, and 8.2%. A similar trend was seen in apo A-1. Copper zinc
      superoxide dismutase and glutathione were raised significantly (P < .001);
      however, changes in glutathione-S-transferase and glutathione peroxidase
      activities were nonsignificant. Malondialdehyde was decreased significantly (P <
      .001). Atorvastatin improves the lipoprotein profile and oxidative status in
      patients with type 2 diabetes.

PMID- 17220474
TI  - Enhanced external counterpulsation: a new modality in the treatment of angina and
      heart failure.

PMID- 17220475
TI  - An isotope-diagnostic approach to Erdheim-Chester's disease of the heart.
AB  - Erdheim-Chester's disease is a form of histiocytic granulomatosis afflicting the
      skeletal system and various inner organs. Apart from incidental findings of
      involvement of various structures and tissues, a complete diagnostic workup to
      evaluate afflicted bodily parts is not known. The authors we present several
      specific isotope-diagnostic techniques of a case to support the identification of
      this rare multisystem infiltrative disease.

PMID- 17220476
TI  - Dietary patterns and diabetes incidence in the Melbourne Collaborative Cohort
      Study.
AB  - The authors investigated the association of dietary patterns and type 2 diabetes
      in a 4-year prospective study of 36,787 adults in the Melbourne Collaborative
      Cohort Study (1990-1994). A total of 31,641 (86%) participants completed follow
      up, and 365 cases were identified. Four factors with eigenvalues of greater than
      2 were identified using the principal factor method with 124 foods/beverages,
      followed by orthogonal rotation. Variables with factor loadings having absolute
      values of 0.3 or greater were used in interpreting the factors. Odds ratios for
      diabetes incidence across quintiles of factor scores were computed by use of
      logistic regression, adjusting for age, energy intake, family history of
      diabetes, country of birth, and other factor scores. Factor 1, characterized by
      olive oil, salad vegetables, and legumes and by avoidance of sweet bakery items,
      margarine, and tea, was associated with country of birth but not with diabetes.
      Factor 2, characterized by salad and cooked vegetables, was inversely associated
      with diabetes. Factor 3, characterized by meats and fatty foods, was associated
      with increased diabetes risk. A range of fruits loaded strongly on factor 4,
      which showed little association with diabetes. Avoidance of a dietary pattern
      including meats and fatty foods, as well as adherence to a pattern including
      salad and cooked vegetables, is recommended.

PMID- 17220477
TI  - Large scale identification of proteins, mucins, and their O-glycosylation in the
      endocervical mucus during the menstrual cycle.
AB  - The mucus filling the human cervical opening blocks the entry to the uterus, but
      this has to be relative and allow for the sperm to penetrate at ovulation. We
      studied this mucus, its content of proteins and mucins, and the mucin O
      glycosylation in cervical secretions before, during, and after ovulation.
      Cervical mucosal secretions from 12 subjects were collected, reduced-alkylated,
      separated with polyacrylamide or agarose/polyacrylamide gel electrophoresis, and
      stained with silver, Alcian blue, or Coomassie Blue stain. Protein and mucin
      bands from before and during ovulation were digested and subsequently analyzed by
      nano-LC-FT-ICR MS and MS/MS. We identified 194 proteins after searches against
      the NCBI non-redundant protein database and an in-house mucin database. Three gel
      forming (MUC5B, MUC5AC, and MUC6) and two transmembrane mucins (MUC16 and MUC1)
      were identified. For the analysis of mucin O-glycosylation, separated mucins from
      six individuals were blotted to PVDF membranes, and the O-glycans were released
      by reductive beta-elimination and analyzed with capillary HPLC-MS and -MS/MS. At
      least 50 neutral, sialic acid-, and sulfate-containing oligosaccharides were
      found. An increase of GlcNAc-6GalNAcol Core 2 structures and a relative decrease
      of NeuAc residues are typical for ovulation, and NeuAc-6GalNAcol and NeuAc-3Gal-
      epitopes are typical for the non-ovulatory phases. The cervical mucus at
      ovulation is thus characterized by a relative increase in neutral fucosylated
      oligosaccharides. This comprehensive characterization of the mucus during the
      menstrual cycle suggests mucin glycosylation as the major alteration at
      ovulation, but the relation to the altered physicochemical properties and sperm
      penetrability is still not understood.

PMID- 17220478
TI  - Proteomics analysis of the interactome of N-myc downstream regulated gene 1 and
      its interactions with the androgen response program in prostate cancer cells.
AB  - NDRG1 is known to play important roles in both androgen-induced cell
      differentiation and inhibition of prostate cancer metastasis. However, the
      proteins associated with NDRG1 function are not fully enumerated. Using
      coimmunoprecipitation and mass spectrometry analysis, we identified 58 proteins
      that interact with NDRG1 in prostate cancer cells. These proteins include nuclear
      proteins, adhesion molecules, endoplasmic reticulum (ER) chaperons, proteasome
      subunits, and signaling proteins. Integration of our data with protein-protein
      interaction data from the Human Proteome Reference Database allowed us to build a
      comprehensive interactome map of NDRG1. This interactome map consists of several
      modules such as a nuclear module and a cell membrane module; these modules
      explain the reported versatile functions of NDRG1. We also determined that serine
      330 and threonine 366 of NDRG1 were phosphorylated and demonstrated that the
      phosphorylation of NDRG1 was prominently mediated by protein kinase A (PKA).
      Further, we showed that NDRG1 directly binds to beta-catenin and E-cadherin.
      However, the phosphorylation of NDRG1 did not interrupt the binding of NDRG1 to E
      cadherin and beta-catenin. Finally, we showed that the inhibition of NDRG1
      expression by RNA interference decreased the ER inducible chaperon GRP94
      expression, directly proving that NDRG1 is involved in the ER stress response.
      Intriguingly, we observed that many members of the NDRG1 interactome are androgen
      regulated and that the NDRG1 interactome links to the androgen response network
      through common interactions with beta-catenin and heat shock protein 90.
      Therefore we overlaid the transcriptomic expression changes in the NDRG1
      interactome in response to androgen treatment and built a dual dynamic picture of
      the NDRG1 interactome in response to androgen. This interactome map provides the
      first road map for understanding the functions of NDRG1 in cells and its roles in
      human diseases, such as prostate cancer, which can progress from androgen
      dependent curable stages to androgen-independent incurable stages.

PMID- 17220479
TI  - CD2 and TCR synergize for the activation of phospholipase Cgamma1/calcium pathway
      at the immunological synapse.
AB  - Upon conjugation with cognate antigen-presenting cells (APCs), T lymphocytes
      undergo a sustained [Ca(2+)](i) increase resulting from the engagement of TCR and
      of accessory molecules with ligands expressed on the surface of APCs. We
      investigated the contribution of the accessory molecule CD2 to the activation of
      phospholipase Cgamma1 (PLCgamma1)/calcium pathway in antigen-stimulated T cells.
      We show that CD2 binding with its ligand CD58 expressed on the surface of APCs
      augments and sustains antigen-induced [Ca(2+)](i) increase in individual T cells
      interacting with APCs. We also show that in conditions in which CD2-CD58
      interaction is impeded, the recruitment of PLCgamma1 to the immunological synapse
      (IS) is reduced. Interestingly, in these conditions PLCgamma1 phosphorylation in
      the regulatory tyrosine 783 is also defective. Our results indicate that TCR- and
      CD2-derived signals converge for the recruitment and activation of PLCgamma1 at
      the IS and shed new light on the accessory function of CD2 in T cell activation
      by specific antigen.

PMID- 17220480
TI  - Unique and conserved functions of B cell-activating factor of the TNF family
      (BAFF) in the chicken.
AB  - The chicken represents the best-characterized animal model for B cell development
      in the so-called gut-associated lymphoid tissue (GALT) and the molecular
      processes leading to B cell receptor diversification in this species are well
      investigated. However, the mechanisms regulating B cell development and
      homeostasis in GALT species are largely unknown. Here we investigate the role
      played by the avian homologue of B cell-activating factor of the tumor necrosis
      factor family (BAFF). Flow cytometric analysis showed that the receptor for
      chicken B cell-activating factor of the tumor necrosis factor family (chBAFF) is
      expressed by mature and immature B cells. Unlike murine and human BAFF, chBAFF is
      primarily produced by B cells both in peripheral lymphoid organs and in the bursa
      of Fabricius, the chicken's unique primary lymphoid organ. In vitro and in vivo
      studies revealed that chBAFF is required for mature B cell survival. In addition,
      in vivo neutralization with a decoy receptor led to a reduction of the size and
      number of B cell follicles in the bursa, demonstrating that, in contrast to
      humans and mice, in chickens BAFF is also required for the development of
      immature B cells. Collectively, we show that chBAFF has phylogenetically
      conserved functions in mature B cell homeostasis but displays unique and thus far
      unknown properties in the regulation of B cell development in birds.

PMID- 17220481
TI  - Evidence for in situ ethanolamine phospholipid adducts with hydroxy-alkenals.
AB  - Hydroxy-alkenals, such as 4-hydroxy-2(E)-nonenal (4-HNE; from n-6 fatty acids),
      are degradation products of fatty acid hydroperoxides, including those generated
      by free radical attack of membrane polyunsaturated fatty acyl moieties. The
      cytotoxic effects of hydroxy-alkenals are well known and are mainly attributable
      to their interaction with different molecules to form covalent adducts. Indeed,
      ethanolamine phospholipids (PEs) can be covalently modified in a cellular system
      by hydroxy-alkenals, such as 4-HNE, 4-hydroxy-2(E)-hexenal (4-HHE; from n-3 fatty
      acids), and 4-hydroxy-dodecadienal (4-HDDE; from the 12-lipoxygenase product of
      arachidonic acid), to form mainly Michael adducts. In this study, we describe the
      formation of PE Michael adducts in human blood platelets in response to oxidative
      stress and in retinas of streptozotocin-induced diabetic rats. We have
      successfully characterized and evaluated, for the first time, PEs coupled with 4
      HHE, 4-HNE, and 4-HDDE by gas chromatography-mass spectrometry measurement of
      their ethanolamine moieties. We also report that aggregation of isolated human
      blood platelets enriched with PE-4-hydroxy-alkenal Michael adducts was altered.
      These data suggest that these adducts could be used as specific markers of
      membrane disorders occurring in pathophysiological states with associated
      oxidative stress and might affect cell function.

PMID- 17220482
TI  - Veterinary medical education for modern food systems: setting a vision and
      creating a strategic plan for veterinary medical education to meet its
      responsibilities.

PMID- 17220483
TI  - Veterinarians in the production setting: where do veterinarians fit in? What can
      they provide? What skills do they need?
AB  - This article examines the changing direction of needed competencies for the
      veterinary medical professional in food-supply veterinary medicine.

PMID- 17220484
TI  - The future of veterinary medicine in poultry production.
AB  - The poultry industry is a highly complex food-animal production system. Its
      success is dependent upon sophisticated techniques and systems to ensure disease
      prevention and product quality. Poultry veterinarians play a key role in the
      overall business and are typically the only individuals within poultry companies
      who are involved in the entire production process, including production
      management, health management, product quality, nutrition, and economics.
      Preparing veterinarians to work effectively in the poultry industry can no longer
      be accomplished within the DVM instructional program. Post-DVM training programs
      specializing in poultry medicine are now producing the veterinarians entering the
      North American poultry industry. Regionalization of training in poultry medicine
      has already taken place. These training programs are very important to food
      animal production in North America; in the future, they must be nurtured and
      supported in order to remain able to supply the veterinary workforce for our
      dynamic poultry industry.

PMID- 17220485
TI  - Animal health: foundation of a safe, secure, and abundant food supply.
AB  - During the past century, reductions in animal diseases have resulted in a safer,
      more uniform, and more economical food supply. In the United States, the passage
      of the 1906 Federal Meat Inspection Act mandated better sanitary conditions for
      slaughter and processing, as well as inspection of live animals and their
      processed products. Following World War II, Congress passed the Poultry Products
      Inspection Act. Both acts are regulated by the Food Safety and Inspection Service
      (FSIS) of the US Department of Agriculture (USDA). The USDA's Animal and Plant
      Health Inspection Service (APHIS) is responsible for regulations governing the
      health of live animals prior to slaughter. This article is a brief overview of
      the ways in which the current predominance of zoonotics among emerging diseases
      underscores the importance of veterinary health professionals and the need for
      continued coordination between animal-health and public-health officials.
      Examples of intersections between animal- and public-health concerns include
      bovine spongiform encephalopathy (BSE) and Johne's disease, as well as extending
      beyond food safety to diseases such as avian influenza (AI). In the United
      States, we have in place an extensive public and private infrastructure to
      address animal-health issues, including the necessary expertise and resources to
      address animal-health emergencies. However, many challenges remain, including a
      critical shortage of food-animal veterinarians. These challenges can be met by
      recruiting and training a cadre of additional food-supply veterinarians, pursuing
      new technologies, collaborating with public-health officials to create solutions,
      and sending a clear and consistent message to the public about important animal
      health issues.

PMID- 17220486
TI  - Veterinarians and the animal-health industry: a complex dimension of opportunity.
AB  - The animal-health industry continues to offer many different opportunities for
      veterinarians interested in business applications for products and ideas vested
      in animal health and animal husbandry. These opportunities are expanding rapidly
      and becoming more diverse every day. Successful animal-health companies are
      increasing the recruiting and retention of business-savvy veterinary
      professionals. Employment earnings and broad offerings of employment extras in
      the animal health industries are in the top strata of the many veterinary
      professional options.

PMID- 17220487
TI  - Food-supply veterinary medicine and veterinary medical education: an Australian
      perspective.
AB  - Food-supply veterinary medicine has been an essential part of veterinary degree
      programs in Australia since the first veterinary school opened in the late
      nineteenth century. Australian veterinary schools, like others internationally,
      are being challenged by the relevance of material in current curricula for modern
      food-supply veterinary medicine. Additionally, student aspirations are a major
      issue, as curriculum designers balance companion-animal training with the
      herd/flock-based issues that focus on productivity and profitability. One of the
      challenges is to examine the relative balance of education in generic skills
      (self-knowledge, change management, teamwork, leadership, negotiation) with more
      technically or scientifically based education. An ongoing process of curriculum
      review and renewal, which involves input from both external and internal
      stakeholders and allows regular review and assessment, is needed to ensure
      continuing curriculum relevance.

PMID- 17220488
TI  - Work conditions, job preparation, and placement strategies for food-animal
      veterinarians.
AB  - This study examines the responses of 1,047 human-resources personnel who recruit
      veterinarians for positions in their organizations. Work conditions in the
      organization, lifestyle and time-management issues, job benefits, job
      expectations, supervisor relations, and the physical demands of veterinary work
      are studied. Comparisons are made between four different occupational areas: food
      animals, mixed animals, companion animals, and industry positions in veterinary
      medicine. The findings portray a career in food animal medicine as very positive.
      Recruiters also make recommendations to colleges of veterinary medicine for
      strategies to improve the preparation and placement of their graduates.

PMID- 17220489
TI  - Academic food-supply veterinarians: future demand and likely shortages.
AB  - The future demand for and potential shortages of food-supply veterinarians have
      been the subject of much concern. Using the Delphi forecasting method in a three
      phase Web-based survey process, a panel of experts identified the trends and
      issues shaping the demand for and supply of academic food-animal veterinarians,
      then forecasted the likely future demand and shortages of food-supply
      veterinarians employed in academic institutions in the United States and Canada
      through 2016. The results indicate that there will be increasing future demand
      and persistent shortages of academic food-supply veterinarians unless current
      trends are countered with targeted, strategic action. The Delphi panel also
      evaluated the effectiveness of several strategies for reversing current trends
      and increasing the number of food-supply veterinarians entering into academic
      careers. Academic food-supply veterinarians are a key link in the system that
      produces food-supply veterinarians for all sectors (private practice, government
      service, etc.); shortages in the academic sector will amplify shortages wherever
      food-supply veterinarians are needed. Even fairly small shortages have
      significant public-health, food-safety, animal-welfare, and bio-security
      implications. Recent events demonstrate that in an increasingly interconnected
      global economic food supply system, national economies and public health are at
      risk unless an adequate supply of appropriately trained food-supply veterinarians
      is available to counter a wide variety of threats ranging from animal and
      zoonotic diseases to bioterrorism.

PMID- 17220490
TI  - Importance-performance analysis of food-supply veterinary medicine career
      commitment.
AB  - This study presents the results of an analysis that identifies factors important
      to veterinary students in making a lifetime commitment to a particular career
      area. Using an importance-performance framework, the study evaluated 28
      veterinary career attributes. Results indicate that to develop greater lifetime
      commitment among students, careers in food-supply veterinary medicine need to
      improve in the areas of health care and retirement benefits, free time available
      for family, opportunities to become authorities in the field, opportunities for
      advancement, and more contact with peer veterinarians.

PMID- 17220491
TI  - Veterinary medical education for modern food systems: past, present, and
      brainstorming a future.
AB  - Concepts presented here were derived from breakout sessions constituted by the 90
      attendees of the Veterinary Medical Education for Modern Food Systems symposium,
      held in Kansas City, Missouri, USA, in October 2005. The attendees were food
      animal educators, veterinary faculty, college deans and administrators, and
      veterinarians employed in government, industry, and private practice. Discussions
      at these breakout sessions focused on four primary areas: (1) determining the
      data needed to document the current demand for food-supply veterinarians (FSVs);
      (2) defining the information/skills/abilities needed within veterinary school
      curricula to address the current demands on FSVs; (3) outlining pre-DVM
      educational requirements needed to support FSVs; and (4) considering the role of
      post-DVM programs in meeting the demand for FSVs.

PMID- 17220492
TI  - Education and the food-systems veterinarian: the impact of new information
      technologies.
AB  - Food systems educators face a double challenge: (1) the inherent change in scope
      and perspective from raising animals to producing safe food in an environmentally
      conscientious manner; and (2) the unprecedented demand for higher education, both
      nationally and internationally. In the modern world, small numbers of producers
      are capable of feeding a growing population. As demographics have shifted from
      rural to urban areas, more global livelihoods are derived from manufacturing and
      services than from agriculture. Education, as one of those services, is
      accounting for an increasing percentage of world trade, through the physical
      translocation of students and, more recently, through online education. Within
      the veterinary realm, colleges outside the United States seek accreditation to
      better compete for students, and there is increasing pressure from private
      schools. Today's food systems require a high level of veterinary expertise, with
      specialization in a particular production system as well as the ability to
      contribute as part of a larger team that can address economic, bio-security,
      biological-waste, animal-welfare, food-safety, and public-health concerns. The
      need for different expertise from food systems specialists (indeed, shortages of
      all types of veterinary specialists), combined with global competition in
      education, is a call to action for the veterinary profession. This is an
      opportunity to revisit and reorganize the delivery of veterinary education,
      making use of new collaborative technologies for greater efficiency and
      effectiveness.

PMID- 17220493
TI  - Veterinary school consortia as a means of promoting the food-supply veterinary
      medicine pipeline.
AB  - Ideas about centers of emphasis and veterinary medical teaching consortia have
      resurfaced to attract students into food-supply veterinary medicine (FSVM). From
      1988 to 2000 a multiple veterinary school consortium approach to food-animal
      production medicine (FAPM) teaching was conducted to handle regional differences
      in case load, faculty strengths, and student interests. Six universities
      developed a memorandum of understanding to provide a wide variety of in-depth,
      species-specific clinical experiences in FAPM to balance their individual
      strengths and weakness in addressing food-animal agriculture, to provide for
      student exchange and faculty development, and to conduct research in food safety.
      Changes in leadership, redirection of funds, failure to publicize the program to
      faculty and students, and a focus on research as opposed to teaching led to
      dissolution of the consortium. However, this approach could work to improve
      recruitment and retention of students in FSVM if it focused on student exchange,
      fostered a more integrated curriculum across schools, encouraged faculty
      involvement, garnered institutional support, and used modern technology in
      teaching. Private veterinary practices as well as public/corporate practices
      could be integrated into a broader food-animal curriculum directed at building
      competency among FSVM students by providing the in-depth training they require.
      Requirements for the success of this type of program will include funding,
      marketing, leadership, communication, coordination, integration, and dedicated
      people with the time to make it work.

PMID- 17220494
TI  - Consortia and centers of excellence: issues and answers.
AB  - As the demand for food-supply veterinarians changes, while the level of expertise
      necessary in this field markedly increases, there is a need to examine
      alternative modalities for delivering food-supply veterinary education. It seems
      clear that not all veterinary schools in the United States can sustain optimally
      sized facilities for the broad-based training in all species of food animals that
      the current and future food-supply veterinarian needs. An alternative model is
      for select schools to establish consortial centers of excellence in specific food
      animal species, to which students from other schools can go for optimum final
      year education. This alternative mode of food supply-veterinary medical education
      is discussed here.

PMID- 17220495
TI  - The concept of rural community practice (RCP).
AB  - The need to devote more human resources to veterinary public practice to cope
      with escalating threats to biological security, public health, and economic
      prosperity, while also addressing societal value changes, has been widely
      recognized and supported. Most envisage increasing the numbers of veterinarians
      in government employment. Why not at least combine this initiative, wherever
      possible, with far greater involvement of rural practitioners to deliver
      contractual public-practice services and provide an enhanced community interface?
      This could make the difference between having a local practice in a community or
      none at all, as well as promising to be more cost effective. The concept of rural
      community practice (RCP) envisages combining traditional services provided in a
      "mixed-animal" veterinary practice with an expanded portfolio of public-practice
      and communication services that meet the emerging animal, public, and ecosystem
      health needs of the collective community, not just those of animal owners. These
      services could include those involving active sentinel surveillance programs for
      both domestic animal and wildlife diseases; on-farm food safety; bio-security;
      traceability and export certification and audit programs; disease investigation,
      including foreign animal diseases; surge capacity emergency response; managing
      for ecosystem health; and client and community education. An expanded practice
      team of animal-health professionals and technologists, led by veterinarians,
      would deliver these services. This RCP approach should have the potential to make
      rural practice more attractive from economic, lifestyle, and job-satisfaction
      perspectives; to enhance the visibility and recognition of the profession; and to
      respond to changing and new societal needs. It also promises to maintain a stable
      network of veterinary practices in rural communities. In addition, the
      recognition of veterinary medicine as a public good should provide for
      consideration of increased investment by levels of government. At the same time,
      this new model could help meet the demands of animal and public-health government
      agencies that face expanding responsibilities during a sustained climate of
      reduced budgetary resources.

PMID- 17220496
TI  - Families, females, and food animals: can we do it all?

PMID- 17220497
TI  - Career opportunities in public health: one veterinarian's experience.
AB  - The veterinary profession is rich in opportunities that are ignored. The
      veterinary profession should evolve to a new level--to more broadly include all
      aspects of public health. Veterinary education, even in its current classical
      mode, provides a rich base for multiple careers. With expansion, there will be a
      wealth of opportunities for veterinarians to be leaders in many phases of
      business and society.

PMID- 17220498
TI  - Hidden costs of food production: the veterinarian's role.
AB  - Veterinarians who work in food-animal production and food safety help to deliver
      food policy by enabling farmers to supply safe, affordable food. However,
      existing food policy reflects a production bias and is increasingly being
      criticized for its hidden costs. These costs include reduced animal welfare, the
      inflated risk of anti-microbial resistance, and the current pandemic of human
      obesity and overweight. Veterinarians do not generally recognize that this is the
      context within which they do their work. In this article, I review this context
      and argue that veterinary students should be taught about it. I also argue that
      the profession should join with food-policy analysts, ethicists, and others who
      are already calling for a rethinking of food policy, so that new policy might
      meet the full wealth of problems and not just some.

PMID- 17220499
TI  - Aspects of future animal health: the Animal Health Foresight Project.
AB  - Against a background of social, political, and environmental change, the
      challenge to provide the most appropriate education for future veterinarians is
      daunting. A consideration of the multiple roles of veterinarians in our future
      society indicates that a different perspective is essential for progress to be
      made. One example of an approach to reach such a perspective is the Animal Health
      Foresight Project, which was jointly sponsored in 2005 by the Canadian Food
      Inspection Agency and the US Department of Agriculture. A new paradigm emerged
      from this study. This article explores the conclusions of this project and their
      potential implications for the future of animal health and for veterinary medical
      education. Outcomes of the Foresight Project led to the development of a new
      paradigm. The implications for and the possible influence on future animal health
      and on veterinary medical education are contemplated.

PMID- 17220500
TI  - The Objective Structured Clinical Examination: three decades of development.
AB  - The Objective Structured Clinical Examination (OSCE) has become a standard for
      performance-based assessment in many health professions. Originally developed for
      assessment in medical schools, the OSCE has been widely adopted for teaching,
      assessment, and certification purposes in most health professions. This article
      outlines the reasons for the rapid uptake of OSCEs and explores some of the key
      features of OSCE development that have implications for use in veterinary
      medicine.

PMID- 17220501
TI  - The Objective Structured Clinical Examination (OSCE) as a determinant of
      veterinary clinical skills.
AB  - The Objective Structured Clinical Examination (OSCE) has become an excellent tool
      to evaluate many elements of a student's clinical skills, especially including
      communication with the patient (human medicine) or client (veterinary medicine);
      eliciting clinical information from these conversations; some aspects of the
      physical examination; and many areas of clinical evaluation and assessment. One
      key factor is that the examination can be structured to compare different
      students' abilities.

PMID- 17220502
TI  - The use of the Objective Structured Clinical Examination (OSCE) in small-animal
      internal medicine and surgery.
AB  - The Objective Structured Clinical Examination (OSCE) has been used extensively to
      evaluate clinical skill of medical students. This article reports on its
      adaptation to veterinary medicine.

PMID- 17220503
TI  - Broadening the public perception of veterinarians: can we keep what we've got
      while transforming ourselves?

PMID- 17220504
TI  - Why veterinary medicine and veterinary medical education needs an accurate census
      of companion animals by household for the United States.

PMID- 17220505
TI  - A philosophy and approach to teaching the epidemiology of food-borne, waterborne,
      and zoonotic diseases.
AB  - Faculty members from veterinary colleges that teach courses on food-borne,
      waterborne, and zoonotic diseases to non-veterinary students face unique
      challenges. The diversity of students' backgrounds, skills, and goals and the
      public nature of the science require some ingenuity in combining good science
      with the ability to communicate clearly in a variety of public forums. Drawing on
      pedagogical theory, the nature of the material, and the diverse abilities of the
      students, we have put together an effective teaching package for non-veterinary
      courses on these subjects, which includes a range of methods from outbreak
      investigations to town hall meetings and food diaries.

PMID- 17220506
TI  - Survey of the large-animal diplomates of the American College of Veterinary
      Internal Medicine regarding knowledge and clinical use of polymerase chain
      reaction: implications for veterinary education.
AB  - A questionnaire was developed to document the knowledge base of large-animal
      diplomates of the American College of Veterinary Internal Medicine (ACVIM)
      regarding polymerase chain reaction (PCR) technology and to identify the common
      use of this technology in equine practice. Ninety-three of the 278 mailed
      questionnaires were returned, for an overall response rate of 33.4%. Ninety
      respondents (99%) reported being familiar with the general principles of nucleic
      acid probe technology; however, only 52 (57%) knew the difference between
      conventional (traditional) and real-time (second-generation) PCR. The majority of
      the respondents (88%) emphasized the need for continuing education on molecular
      diagnostics. Eighty-four (92%) of the respondents regularly use PCR (conventional
      and/or real-time) for the detection of equine pathogens, and 80 (88%) commonly
      submit their samples to university/state veterinary laboratories. Blood, nasal
      swabs, and feces are the three equine specimens most commonly submitted for PCR
      analysis of Streptococcus equi, Lawsonia intracellularis, Neorickettsia risticii,
      equine herpesvirus 1/4, Rhodococcus equi, Sarcocystis neurona, and equine
      influenza virus. Diplomates reported costs associated with molecular diagnostics
      and unreliability of PCR as the most common limitations of PCR. Didactic training
      in veterinary curricula and during continuing-education opportunities continues
      to be necessary to produce veterinarians who have an understanding of the
      clinical applications of molecular diagnostics.

PMID- 17220507
TI  - Hawaii veterinarians' bioterrorism preparedness needs assessment survey.
AB  - The purpose of this study was to assess the objective bioterrorism-related
      knowledge base and the perceived response readiness of veterinarians in Hawaii to
      a bioterrorism event, and also to identify variables associated with knowledge
      based test performance. An anonymous survey instrument was mailed to all licensed
      veterinarians residing in Hawaii (N = 229) up to three times during June and July
      2004, using numeric identifiers to track non-respondents. The response rate for
      deliverable surveys was 59% (125 of 212). Only 12% (15 of 123) of respondents
      reported having had prior training on bioterrorism. Forty-four percent (55 of
      125) reported being able to identify a bioterrorism event in animal populations;
      however, only 17% (21 of 125) felt able to recognize a bioterrorism event in
      human populations. Only 16% (20 of 123) felt they were able to respond
      effectively to a bioterrorist attack. Over 90% (106 of 116) expressed their
      willingness to provide assistance to the state in its response to a bioterrorist
      event. Veterinarians scored a mean of 70% correct (5.6 out of 8 questions) on the
      objective knowledge-based questions. Additional bioterrorism preparedness
      training should be made available, both in the form of continuing educational
      offerings for practicing veterinarians and as a component of the curriculum in
      veterinary schools.

PMID- 17220508
TI  - Medical Imaging Resource Center (MIRC) for veterinary medicine: a digital image
      teaching file.
AB  - RATIONALE FOR THE STUDY: Veterinary radiology has a need for software to
      facilitate the creation of digital image teaching files. The Medical Imaging
      Resource Center (MIRC) is widely used in medicine to create teaching cases and
      store data from clinical trials. This open-source software was identified as a
      solution for use in veterinary medicine. METHODOLOGY: The additional fields
      needed to adapt the system for veterinary use were identified as sex, species,
      and breed. Breed and species codes from the Matthew J. Ryan Veterinary Hospital
      of the University of Pennsylvania and from the Standard Nomenclature of
      Veterinary Diseases and Operations (SNVDO) were gathered and correlated. RESULTS:
      The sex fields added were male, male neutered, female, and female neutered. The
      breed and species codes were combined into a single term. These were coded in
      eXtensible Markup Language (XML) and added to the software's veterinary document
      template and search capabilities. CONCLUSIONS: MIRC was successfully adapted for
      use in creating digital teaching files for veterinary medicine.

PMID- 17220510
TI  - Solving the distal reward problem through linkage of STDP and dopamine signaling.
AB  - In Pavlovian and instrumental conditioning, reward typically comes seconds after
      reward-triggering actions, creating an explanatory conundrum known as "distal
      reward problem": How does the brain know what firing patterns of what neurons are
      responsible for the reward if 1) the patterns are no longer there when the reward
      arrives and 2) all neurons and synapses are active during the waiting period to
      the reward? Here, we show how the conundrum is resolved by a model network of
      cortical spiking neurons with spike-timing-dependent plasticity (STDP) modulated
      by dopamine (DA). Although STDP is triggered by nearly coincident firing patterns
      on a millisecond timescale, slow kinetics of subsequent synaptic plasticity is
      sensitive to changes in the extracellular DA concentration during the critical
      period of a few seconds. Random firings during the waiting period to the reward
      do not affect STDP and hence make the network insensitive to the ongoing activity
      the key feature that distinguishes our approach from previous theoretical
      studies, which implicitly assume that the network be quiet during the waiting
      period or that the patterns be preserved until the reward arrives. This study
      emphasizes the importance of precise firing patterns in brain dynamics and
      suggests how a global diffusive reinforcement signal in the form of extracellular
      DA can selectively influence the right synapses at the right time.

PMID- 17220511
TI  - Analysis of p53 protein expression levels on ovarian cancer tissue microarray
      using automated quantitative analysis elucidates prognostic patient subsets.
AB  - BACKGROUND: p53 protein is regarded as a valuable prognostic marker in cancer
      with a potential use as a molecular target. Here, we sought to determine the
      prognostic value of p53 in ovarian cancer using a novel method of
      compartmentalized in situ protein analysis. PATIENTS AND METHODS: A tissue array
      composed of 141 advanced stage ovarian cancers uniformly treated was constructed.
      For evaluation of p53 protein expression, we used an immunofluorescence-based
      method of automated in situ quantitative measurement of protein analysis (AQUA).
      RESULTS: High nuclear p53 expression levels were associated with better outcome
      for overall survival (OS) (P = 0.0023) and disease-free survival (P = 0.0338) at
      5-years. High cytoplasmic p53 expression levels were associated with better
      outcome for OS (P = 0.0002). In multivariable analysis, high nuclear and high
      cytoplasmic p53 level with International Federation of Gynecology and Obstetrics
      (FIGO) stage were the most significant predictor variables for OS and high
      nuclear p53 level with FIGO stage were the significant predictor variables for
      disease-free survival. CONCLUSIONS: Assessment of the prognostic value of p53
      protein levels using conventional immunohistochemistry is limited by the
      nonquantitative nature of the method. AQUA provides precise estimation of p53
      protein levels and was able to elucidate the association of p53 protein levels
      and ovarian cancer prognosis.

PMID- 17220512
TI  - The effect of Glc6P uptake and its subsequent oxidation within pea root plastids
      on nitrite reduction and glutamate synthesis.
AB  - In roots, nitrate assimilation is dependent upon a supply of reductant that is
      initially generated by oxidative metabolism including the pentose phosphate
      pathway (OPPP). The uptake of nitrite into the plastids and its subsequent
      reduction by nitrite reductase (NiR) and glutamate synthase (GOGAT) are
      potentially important control points that may affect nitrate assimilation. To
      support the operation of the OPPP there is a need for glucose 6-phosphate (Glc6P)
      to be imported into the plastids by the glucose phosphate translocator (GPT).
      Competitive inhibitors of Glc6P uptake had little impact on the rate of Glc6P
      dependent nitrite reduction. Nitrite uptake into plastids, using (13)N labelled
      nitrite, was shown to be by passive diffusion. Flux through the OPPP during
      nitrite reduction and glutamate synthesis in purified plastids was followed by
      monitoring the release of (14)CO(2) from [1-(14)C]-Glc6P. The results suggest
      that the flux through the OPPP is maximal when NiR operates at maximal capacity
      and could not respond further to the increased demand for reductant caused by the
      concurrent operation of NiR and GOGAT. Simultaneous nitrite reduction and
      glutamate synthesis resulted in decreased rates of both enzymatic reactions. The
      enzyme activity of glucose 6-phosphate dehydrogenase (G6PDH), the enzyme
      supporting the first step of the OPPP, was induced by external nitrate supply.
      The maximum catalytic activity of G6PDH was determined to be more than sufficient
      to support the reductant requirements of both NiR and GOGAT. These data are
      discussed in terms of competition between NiR and GOGAT for the provision of
      reductant generated by the OPPP.

PMID- 17220513
TI  - Cell division in the unicellular microalga Dunaliella viridis depends on
      phosphorylation of extracellular signal-regulated kinases (ERKs).
AB  - In mammalian cells, MAPKs are involved in both stress response (JNK and p38
      pathways) and cell proliferation and differentiation [extracellular signal
      regulated kinase (ERK)] through protein kinase cascades. Exposure of Dunaliella
      viridis cell cultures to PD98059, a very specific inhibitor of the ERK signalling
      pathway, resulted in a total arrest of cell proliferation and a complete
      dephosphorylation of ERK. As shown by flow cytometry analysis of propidium iodide
      stained cells, PD98059 stopped mitosis at the G(2) phase after the S phase has
      been completed. Multiple physiological parameters such as cell motility and
      reducing power generation (NADPH) clearly indicate that the treated cells are
      wholly viable. Exposure of D. viridis to environmental stresses that impair cell
      division, such as hyperosmotic shock, nitrogen starvation, or sublethal UV
      irradiation, caused a marked decrease in the phospho-ERK levels as detected by
      western blot. Two 400 bp polynucleotides from D. viridis with high homologies to
      published sequences of ERK1 and ERK2 were cloned, sequenced, and submitted to
      GenBank. Northern blot analysis revealed two mRNA bands of approximately 1.9 kb,
      consistent with the expected size of ERK proteins ( approximately 40 kDa).
      Sequence analysis showed that they contained several mitogen-activated protein
      kinase (MAPK) conserved domains, including II, III, VIb, VII, and the double
      phosphorylation motif. Interestingly, in D. viridis, this motif was T*DY* instead
      of the canonic T*EY*. Based on this finding, ERK plant sequences can be divided
      into two groups, one termed the T*DY* branch and the other termed the T*EY*
      branch. The molecular and functional data presented here suggest that ERK is a
      very ancient signalling pathway and that it was already present in the last
      common ancestor of all eukaryotic cells.

PMID- 17220514
TI  - Microarray gene expression profiling of developmental transitions in Sitka spruce
      (Picea sitchensis) apical shoots.
AB  - The apical shoot drives the yearly new stem growth of conifer trees, is the
      primary site for the establishment of chemical and physical defences, and is
      important in establishing subsequent perennial growth. This organ presents an
      interesting developmental system, with growth and development progressing from a
      meristematic tip through development of a primary vascular system, to a base with
      fully differentiated and lignified secondary xylem on the inside and bark tissue
      with constitutive defence structures such as resin, polyphenolic phloem
      parenchyma cells, and sclereids on the outside. A spruce (Picea spp.) microarray
      containing approximately 16.7K unique cDNAs was used to study transcript profiles
      that characterize the developmental transition in apical shoots of Sitka spruce
      (Picea sitchensis) from their vegetative tips to their woody bases. Along with
      genes involved in cell-wall modification and lignin biosynthesis, a number of
      differentially regulated genes encoding protein kinases and transcription factors
      with base-preferred expression patterns were identified, which could play roles
      in the formation of woody tissues inside the apical shoot, as well as in
      regulating other developmental transitions associated with organ maturation.
      Preferential expression of known conifer defence genes, genes encoding defence
      related proteins, and genes encoding regulatory proteins was observed at the
      apical shoot tip and in the green bark tissues at the apical shoot base,
      suggesting a commitment to constitutive defence in the apical shoot that is co
      ordinated with rapid development of secondary xylem.

PMID- 17220515
TI  - Quantification of plant stress using remote sensing observations and crop models:
      the case of nitrogen management.
AB  - Remote sensing techniques offer a unique solution for mapping stress and
      monitoring its time-course. This article reviews the main issues to be addressed
      for quantifying stress level from remote sensing observations, and to mitigate
      its impact on crop production by managing cultural practices. The case of
      nitrogen fertilization is used here as a paradigm. The derivation of canopy state
      variables such as the leaf area index (LAI) and chlorophyll content (C(ab)) is
      first addressed. It is demonstrated that the inversion of radiative transfer
      models leads to useful estimates of these variables. However, because of the ill
      posed nature of the inverse problem, better accuracy is achieved when using prior
      information on the distribution of the variables and when multiplying LAI by
      C(ab) to get canopy level chlorophyll content. This variable, LAIxC(ab) is well
      suited for quantifying canopy level nitrogen content. It is used for nitrogen
      stress evaluation by comparison with a reference unstressed situation which is,
      however, not easy to get in practice. The combination of remote sensing
      observations with crop models provides an elegant solution for stress
      quantification through assimilation approaches. It fuses several sources of
      information within our knowledge of the processes involved and accounts for the
      environmental budget which can be integrated when making decisions about cultural
      practices. Conclusions are drawn on the issues related to the retrieval of canopy
      state variables from remote sensing data, to the link between these observables
      and crop models, and to the assimilation approaches. Avenues for further research
      are finally discussed along with the required observation system.

PMID- 17220516
TI  - Compensatory evolution in response to a novel RNA polymerase: orthologous
      replacement of a central network gene.
AB  - A bacteriophage genome was forced to evolve a new system of regulation by
      replacing its RNA polymerase (RNAP) gene, a central component of the phage
      developmental pathway, with that of a relative. The experiment used the obligate
      lytic phage T7 and the RNAP gene of phage T3. T7 RNAP uses 17 phage promoters,
      which are responsible for all middle and late gene expression, DNA replication,
      and progeny maturation, but the enzyme has known physical contacts with only 2
      other phage proteins. T3 RNAP was supplied in trans by the bacterial host to a T7
      genome lacking its own RNAP gene and the phage population was continually
      propagated on naive bacteria throughout the adaptation. Evolution of the T3 RNAP
      gene was thereby prevented, and selection was for the evolution of regulatory
      signals throughout the phage genome. T3 RNAP transcribes from T7 promoters only
      at low levels, but a single mutation in the promoter confers high expression,
      providing a ready mechanism for reevolution of gene expression in this system.
      When selected for rapid growth, fitness of the engineered phage evolved from a
      low of 5 doublings/h to 33 doublings/h, close to the expected maximum of 37
      doublings/h. However, the experiment was terminated before it could be determined
      accurately that fitness had reached an obvious plateau, and it is not known
      whether further adaptation could have resulted in complete recovery of fitness.
      More than 30 mutations were observed in the evolved genome, but changes were
      found in only 9 of the 16 promoters, and several coding changes occurred in genes
      with no known contacts with the RNAP. Surprisingly, the T7 genome adapted to T3
      RNAP also maintained high fitness when using T7 RNAP, suggesting that the extreme
      incompatibility of T7 elements with T3 RNAP is not an invariant property of
      divergence in these expression systems.

PMID- 17220517
TI  - Numerical modeling of odorant uptake in the rat nasal cavity.
AB  - An anatomically accurate 3-dimensional numerical model of the right rat nasal
      cavity was developed and used to compute low, medium, and high flow rate
      inspiratory and expiratory mucosal odorant uptake (imposed patterning) for 3
      odorants with different mucus solubilities. The computed surface mass flux
      distributions were compared with anatomic receptor gene expression zones
      identified in the literature. In general, simulations predicted that odorants
      that were highly soluble in mucus were absorbed dorsally and medially,
      corresponding roughly to receptors from one of the gene expression zones.
      Insoluble odorants tended to be absorbed more peripherally in the rat olfactory
      region corresponding to the other 2 zones. These findings also agreed in general
      with the electroolfactogram measurements and the voltage-sensitive dye
      measurements reported in the literature. This numerical approach is the first to
      predict detailed odorant flux information across the olfactory mucosa in the rat
      nasal cavity during inspiratory and expiratory flow and to relate it to anatomic
      olfactory receptor location, physiological function, and biochemical experiment.
      This numerical technique can allow us to separate the contributions of imposed
      and inherent patterning mechanisms on the rat olfactory mucosa.

PMID- 17220518
TI  - A complex relationship among chemical concentration, detection threshold, and
      suprathreshold intensity of bitter compounds.
AB  - Detection thresholds and psychophysical curves were established for caffeine,
      quinine-HCl (QHCl), and propylthiouracil (PROP) in a sample of 33 subjects (28
      female mean age 24 +/- 4). The mean detection threshold (+/-standard error) for
      caffeine, QHCl, and PROP was 1.2 +/- 0.12, 0.0083 +/- 0.001, and 0.088 +/- 0.07
      mM, respectively. Pearson product-moment analysis revealed no significant
      correlations between detection thresholds of the compounds. Psychophysical curves
      were constructed for each bitter compound over 6 concentrations. There were
      significant correlations between incremental points of the individual
      psychophysical curves for QHCl and PROP. Regarding caffeine, there was a specific
      concentration (6 mM) below and above which the incremental steps in bitterness
      were correlated. Between compounds, analysis of psychophysical curves revealed no
      correlations with PROP, but there were significant correlations between the
      bitterness of caffeine and QHCl at higher concentrations on the psychophysical
      curve (P<0.05). Correlation analysis of detection threshold and suprathreshold
      intensity within a compound revealed a significant correlation between PROP
      threshold and suprathreshold intensity (r=0.46-0.4, P<0.05), a significant
      negative correlation for QHCl (r=-0.33 to -0.4, P<0.05), and no correlation for
      caffeine. The results suggest a complex relationship between chemical
      concentration, detection threshold, and suprathreshold intensity.

PMID- 17220519
TI  - Modeling inspiratory and expiratory steady-state velocity fields in the Sprague
      Dawley rat nasal cavity.
AB  - Distribution patterns of odorant molecules in the rat nasal olfactory region
      depend in large part on the detailed airflow patterns in the nasal cavity, which
      in turn depend on the anatomical structure. To investigate these flow patterns,
      we constructed an anatomically accurate finite element model of the right nasal
      cavity of the Sprague-Dawley rat based on horizontal (anterior-posterior) nasal
      cast cross sections. By numerically solving the fluid mechanical momentum and
      continuity equations using the finite element method, we studied the flow
      distribution and the complete velocity field for both inspiration and expiration
      throughout the nasal cavity under physiological flow rates of resting breathing
      and sniffing. Detailed velocity profiles, volumetric flow distributions, and
      streamline patterns for quasi-steady airflow are presented. S-shaped streamlines
      passing through the olfactory region are found to be less prevalent during
      expiratory than inspiratory flow leading to trapping and an increase in odorant
      molecule retention in the olfactory region during sniffing. The rat nasal
      velocity calculations will be used to study the distribution of odorant uptake
      onto the rat olfactory mucosa and compare it with the known anatomic location of
      some types of rat olfactory receptors.

PMID- 17220520
TI  - Compatibility of a bivalent modified-live vaccine against Bordetella
      bronchiseptica and CPiV, and a trivalent modified-live vaccine against CPV, CDV
      and CAV-2.
AB  - Eight puppies (group 1) were vaccinated once with a bivalent modified-live
      vaccine against infectious tracheobronchitis by the intranasal route and at the
      same time with an injectable trivalent vaccine against canine parvovirus, canine
      distemper virus and canine adenovirus; a second group of eight puppies (group 2)
      was vaccinated only with the intranasal bivalent vaccine, and a further eight
      puppies (group 3) were vaccinated only with the injectable trivalent vaccine.
      Three weeks later they were all challenged with wildtype Bordetella
      bronchiseptica and canine parainfluenza virus by the aerosol route, and their
      antibody responses to the five vaccine organisms were determined. Oronasal swabs
      were taken regularly before and after the challenge for the isolation of bacteria
      and viruses, and the puppies were observed for clinical signs for three weeks
      after the challenge. There were no significant differences in the puppies' titres
      against canine parvovirus, canine distemper virus and canine adenovirus type 2
      between the groups vaccinated with or without the bivalent intranasal vaccine.
      After the challenge the mean clinical scores of the two groups vaccinated with
      the intranasal vaccine were nearly 90 per cent lower (P=0.001) than the mean
      score of the group vaccinated with only the trivalent injectable vaccine, and the
      puppies in this group all became culture-positive for B bronchiseptica and canine
      parainfluenza virus. There were only small differences between the rates of
      isolation of B bronchiseptica from groups 1, 2 and 3, but significantly lower
      yields of canine parainfluenza virus were isolated from groups 1 and 2 than from
      group 3.

PMID- 17220521
TI  - Behavioural responses of poultry during kosher slaughter and their implications
      for the birds' welfare.
AB  - Measurements were made during Shechita (kosher) slaughter of 692 meat chickens,
      including the behaviour of the birds during the procedure and the times from
      their removal from the crate, to neck cutting, bleed-out and shackling. Four of
      100 birds showed a mild physical response to neck cutting but the others showed
      no response. Approximately 60 per cent of the birds showed a physical response to
      touching the eye or eyelid at up to 5 seconds after neck cutting, but by 15
      seconds none showed this response. The birds became unable to retain their
      posture and suffered involuntary muscular contractions at 12 to 15 seconds after
      neck cutting and had lost approximately 40 per cent of their total blood volume
      by 30 seconds after neck cutting.

PMID- 17220522
TI  - Exploratory study of Mycoplasma suis (Eperythrozoon suis) on four commercial pig
      farms in southern Brazil.
AB  - Mycoplasma suis (Eperythrozoon suis) was detected by PCR and Southern blot in 186
      pigs (121 sows, 61 piglets and four boars) on four farms in southern Brazil. DNA
      was extracted from blood samples and a 16S rRNA gene fragment of M suis was
      amplified by PCR; Southern blot analysis was then performed on all the samples.
      Twenty-two of the sows (18.2 per cent) were positive by PCR, and 40 (33.1 per
      cent) were positive by Southern blot; only one piglet and one boar were positive.
      The packed cell volume and total plasma protein of the pigs and their PCR and
      Southern blot results were not significantly different on the four farms, but
      higher proportions of the pigs were positive by Southern blot than by PCR
      (P<0.05). The packed cell volume and total plasma protein concentrations of the M
      suis positive and negative sows were not significantly different.

PMID- 17220523
TI  - Assessing the risk of windborne spread of bluetongue in the 2006 outbreak of
      disease in northern Europe.

PMID- 17220524
TI  - Transitional cell papilloma and leiomyoma of the urinary bladder in two goats.

PMID- 17220525
TI  - Detection of African swine fever virus genomic DNA in a Nigerian red river hog
      (Potamochoerus porcus).

PMID- 17220526
TI  - Rameshwarotrema uterocrescens trematode parasitism of the oesophageal glands in
      green sea turtles (Chelonia mydas).

PMID- 17220527
TI  - BVA/KC hip and elbow dysplasia schemes.

PMID- 17220528
TI  - FMD and the contiguous cull.

PMID- 17220529
TI  - Communication skills.

PMID- 17220530
TI  - Lysosomal unesterified cholesterol content correlates with liver cell death in
      murine Niemann-Pick type C disease.
AB  - Niemann-Pick type C (NPC) disease is a multisystem disorder resulting from
      mutations in the NPC1 gene that encodes a protein involved in intracellular
      cholesterol trafficking. Significant liver dysfunction is frequently seen in
      patients with this disease. The current studies used npc1 mutant mice to
      investigate the association between liver dysfunction and unesterified
      cholesterol accumulation, a hallmark of NPC disease. Data from 92 npc1(-/-) mice
      (age range, 9-56 days) revealed a significant positive correlation between the
      plasma activities of alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) and whole liver cholesterol content. In 56 day old npc1(-/
      ) mice that had been fed from 35 days of age a rodent diet or the same diet
      containing either cholesterol (1.0%, w/w) or ezetimibe (a sterol absorption
      inhibitor; 0.0125%, w/w), whole liver cholesterol content averaged 33.5 +/- 1.1,
      87.9 +/- 1.7, and 20.8 +/- 0.9 mg, respectively. Again, plasma ALT and AST
      activities were positively correlated with hepatic cholesterol content. In
      contrast, plasma transaminase levels remained in the normal range in npc1(+/+)
      mice, in which hepatic esterified cholesterol content had been increased by 72
      fold by feeding a high-cholesterol, high-fat diet. These studies suggest that the
      late endosomal/lysosomal content of unesterified cholesterol correlates with cell
      damage in NPC disease.

PMID- 17220531
TI  - Myelin-associated glycoprotein-mediated signaling in central nervous system
      pathophysiology.
AB  - The myelin-associated glycoprotein (MAG) is a type I membrane-spanning protein
      expressed exclusively in oligodendrocytes and Schwann cells. It has two generally
      known pathophysiological roles in the central nervous system (CNS): maintenance
      of myelin integrity and inhibition of CNS axonal regeneration. The subtle CNS
      phenotype resulting from genetic ablation of MAG expression has made mechanistic
      analysis of its functional role in these difficult. However, the past few years
      have brought some major revelations, particularly in terms of mechanisms of MAG
      signaling through the Nogo-66 receptor (NgR) complex. Although apparently
      converging through NgR, a readily noticeable fact is that the neuronal growth
      inhibitory effect of MAG differs from that of Nogo-66. This may result from the
      influence of coreceptors in the form of gangliosides or from MAG-specific
      neuronal receptors such as NgR2. MAG has several other neuronal binding partners,
      and some of these may modulate its interaction with the NgR complex or downstream
      signaling. This article discusses new findings in MAG-forward and -reverse
      signaling and its role in CNS pathophysiology.

PMID- 17220532
TI  - Nicotine and hippocampus-dependent learning: implications for addiction.
AB  - Addiction is a complex disorder because many factors contribute to the
      development and maintenance of addiction. One factor is learning. For example,
      drug-context associations that develop during drug use could facilitate drug
      craving upon re-exposure to contexts previously associated with drugs.
      Additionally, deficits in cognitive processes associated with withdrawal could
      precipitate relapse in attempts to ameliorate those deficits. Because addiction
      and learning involve common neural areas and cell signaling cascades, addiction
      related changes in processes underlying plasticity may contribute to addiction.
      This article examines similarities between addiction and learning at the
      behavioral, neural, and cellular levels, with emphasis on the neural substrates
      underlying the effects of acute nicotine, chronic nicotine, and withdrawal from
      chronic nicotine on hippocampus-dependent contextual learning.

PMID- 17220534
TI  - Ever-expanding network of dynamin-interacting proteins.
AB  - Clathrin-mediated endocytosis is a major cellular pathway for internalization of
      proteins and lipids and for recycling of synaptic vesicles. The GTPase dynamin
      plays a key role in this process, and the proline-rich domain of dynamin
      participates in various protein-protein interactions to ensure a proper
      coordination of endocytic processes. Although dynamin is not directly associated
      with actin, several dynamin-binding proteins can interact with actin or with
      proteins that regulate actin assembly, thereby coordinately regulating actin
      assembly and trafficking events. This article summarizes dynamin interactions
      with various Src homology 3-containing proteins, many of which are actin-binding
      proteins. It also discusses the recently identified two new dynamin binding
      proteins, SH3 protein interacting with Nck, 90 kDa/Wiskott-Aldrich syndrome
      protein interacting with SH3 protein (SPIN90/WISH) and sorting nexin 9, and
      outlines their potential role as a link between endocytosis and actin dynamics.

PMID- 17220533
TI  - Molecular profiling of antipsychotic drug function: convergent mechanisms in the
      pathology and treatment of psychiatric disorders.
AB  - Despite great progress in antipsychotic drug research, the molecular mechanisms
      by which these drugs work have remained elusive. High-throughput gene profiling
      methods have advanced this field by allowing the simultaneous investigation of
      hundreds to thousands of genes. However, different methodologies, choice of brain
      region, and drugs studied have made comparisons across different studies
      difficult. Because of the complexity of gene expression changes caused by drugs,
      teasing out the most relevant expression differences is a challenging task. One
      approach is to focus on gene expression changes that converge on the same systems
      that were previously deemed important to the pathology of psychiatric disorders.
      From the microarray studies performed on human postmortem brain samples from
      schizophrenics, the systems most implicated to be dysfunctional are synaptic
      machinery, oligodendrocyte/myelin function, and mitochondrial/ubiquitin
      metabolism. Drugs may act directly or indirectly to compensate for underlying
      pathological deficits in schizophrenia or via other mechanisms that converge on
      these pathways. Side effects, consisting of motor and metabolic dysfunction
      (which occur with typical and atypical drugs, respectively), also may be mediated
      by gene expression changes that have been reported in these studies. This article
      surveys both the convergent antipsychotic mechanisms and the genes that may be
      responsible for other effects elicited by antipsychotic drugs.

PMID- 17220536
TI  - Cytisine for the treatment of nicotine addiction: from a molecule to therapeutic
      efficacy.
AB  - Cytisine, a natural plant alkaloid, has been marketed in Central and Eastern
      Europe for over 40 years for the clinical management of smoking cessation.
      Despite the fact that cytisine has been used by millions of smokers, its
      characteristics have not been reviewed in scientific literature in English, and
      presently existing clinical studies on its effectiveness and safety are
      insufficient to warrant licensing by modern standards. Understanding of the
      mechanism of cytisine action as a smoking cessation aid provides a necessary
      basis for conducting clinical trials to confirm its efficacy as an optimal
      antismoking therapy. Hereafter, we present a review of current knowledge about
      the pharmacokinetics, pharmacodynamics, toxicity, therapeutic efficacy and safety
      of cytisine, and about its derivatives that are under development. Recent
      pharmacological research has elucidated that the drug is a low efficacy partial
      agonist of alpha4beta2 nicotinic acetylcholine receptors, which are believed to
      be central to the effect of nicotine (NIC) on the reward pathway. The drug
      reduces the effects of NIC on dopamine release in the mesolimbic system when
      given alone, while simultaneously attenuating NIC withdrawal symptoms that
      accompany cessation attempts. Clinical studies on cytisine as a smoking cessation
      aid have demonstrated that the drug is effective and safe. Our recent
      uncontrolled trial has shown that a 12-month carbon monoxide-verified continuous
      abstinence rate following a standard course of treatment with cytisine with
      minimal behavioral support is similar (13.8%; N = 436) to that observed following
      treatment with NIC replacement therapy. Since cytisine exhibits a desirable
      pharmacological profile which makes it an attractive smoking cessation drug, it
      should be advanced to randomized clinical trials. However, more detailed
      preclinical studies on its pharmacokinetics and safety profile are required.

PMID- 17220535
TI  - Running to stand still: ionotropic receptor dynamics at central and peripheral
      synapses.
AB  - For synapses to form and function, neurotransmitter receptors must be recruited
      to a location on the postsynaptic cell in direct apposition to presynaptic
      neurotransmitter release. However, once receptors are inserted into the
      postsynaptic membrane, they are not fixed in place but are continually exchanged
      between synaptic and extrasynaptic regions, and they cycle between the surface
      and intracellular compartments. This article highlights and compares the current
      knowledge about the dynamics of acetylcholine receptors at the vertebrate
      peripheral neuromuscular junction and AMPA, N-methyl-D-aspartate, and gamma
      aminobutyric acid receptors in central synapses.

PMID- 17220537
TI  - Transforming growth factor beta and cardiovascular diseases: the other facet of
      the 'protective cytokine'.
AB  - Transforming growth factor beta (TGF-beta) is a cytokine engaged in a wide range
      of diverse and often contradictory functions. Its effect on the cardiovascular
      system is also ambiguous; on the one hand, there is a strong evidence for so
      called 'protective cytokine hypothesis'considering TGF-beta to be an anti
      atherogenic and plaque-stabilizing factor, but on the other hand, TGF-beta has
      been proven to exert some proinflammatory effects. Moreover, besides the positive
      aspect of a profibrotic and reparative action of TGF-beta, there are also some
      disadvantages: TGF-beta plays a significant role in postangioplasty restenosis,
      post-infarction myocardial remodeling (resulting in the development of heart
      failure) and in numerous other circulatory disorders where fibrosis and vascular
      remodeling takes part in pathology. The aim of the paper was to review and
      discuss the unwanted effects of TGF-beta in the circulatory system, and to
      outline the possible pharmacological strategies to interfere with TGF-beta
      dependent pathways and prevent these disturbances.

PMID- 17220538
TI  - Involvement of cannabinoid CB1 receptors in drug addiction: effects of rimonabant
      on behavioral responses induced by cocaine.
AB  - A lot of evidence indicate that endocannabinoids and cannabinoid CB(1) receptors
      are implicated in drug addiction. In the present study, we investigated the
      effect of the cannabinoid CB(1) receptor antagonist/partial agonist rimonabant on
      the cocaine-maintained reinforcement and relapse to cocaine seeking as well as on
      the cocaine challenge-induced hyperactivity in sensitized rats and on
      discriminative stimulus effects of cocaine in rats. We found that
      endocannabinoids were not involved in maintenance of cocaine reinforcement and
      its subjective effects since pharmacological blockade of cannabinoid CB(1)
      receptors altered neither self-administration nor discriminative stimulus effects
      of cocaine. On the other hand, withdrawal from repeated access or exposure to
      cocaine and then a reinstatement of cocaine-seeking behavior or a sensitized
      locomotor response to a single cocaine challenge, respectively, was potently
      reduced by pretreatment with rimonabant. The latter observations may show that
      repeated cocaine treatment and the drug withdrawal produce--apart from behavioral
      effects--also different neural consequences in the endocannabinoid systems in
      rats.

PMID- 17220539
TI  - Anxiolytic-like effects of group III mGlu receptor ligands in the hippocampus
      involve GABAA signaling.
AB  - Recent literature data and the results of our earlier pharmacological studies,
      have provided evidence that antagonists of group I metabotropic glutamate
      receptors (mGluRs) and agonists of group II mGluRs show anxiolytic-like
      properties in preclinical and clinical studies. Out of all glutamate receptors,
      the role of group III mGluRs in anxiety-like states is the least investigated
      because of the lack of specific pharmacological tools, moreover all group III
      receptor ligands synthesized so far are not systemically active, so they have to
      be administered centrally. In the present study, we investigated the anxiolytic
      like activity of group III mGlu receptor ligands including a nonselective group
      III mGlu receptor agonist (1S,3R,4S)-1-aminocyclopentane-1,3,4-tricarboxylic acid
      (ACPT-I), group III mGlu receptor antagonist, (RS)-alpha -cyclopropyl-4
      phosphonophenylglycine (CPPG) and a positive allosteric modulator of mGluR4 (-)-N
      phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC). The Vogel
      conflict drinking test in rats was used to test the anxiolytic-like effects. The
      hippocampus was chosen as a site of the injection of drugs, as this brain regions
      is involved in the regulation of anxiety-related behavior. Intrahippocampal
      injections (CA1 region of the hippocampus) of PHCCC (12 nmol) but not of CPPG (75
      nmol ) produced an anxiolytic-like response, moreover, the effect of PHCCC was
      totally blocked by CPPG. The anxiolytic-like effects of ACPT-I (7.5 nmol) or
      PHCCC (12 nmol) were significantly attenuated by flumazenil (10 mg/kg),
      indicating an involvement of GABAergic system in the anxiolytic-like response.

PMID- 17220540
TI  - Effect of cocaine sensitization on alpha1-adrenoceptors in brain regions of the
      rat: an autoradiographic analysis.
AB  - We investigated the effects of repeated intermittent cocaine treatment, resulting
      in behavioral sensitization, on the density of alpha(1)-adrenoceptors in the rat
      brain measured by quantitative in vitro autoradiography of [(3)H]prazosin.
      Animals were decapitated following a short (2 h) and long (48 h) withdrawal
      period after an injection of cocaine (10 mg/kg) on day 10 given to either cocaine
      naive (saline daily, days 1-5) or cocaine-sensitized (cocaine 10 mg/kg daily,
      days 1-5) rats. In cocaine-naive rats, significant decreases in alpha(1)
      adrenoceptors 2 h after a single dose of cocaine were observed in the amygdaloid
      nuclei and hippocampus; the decreases in the centromedial nucleus of the amygdala
      persisted until 48th hour of withdrawal. On the contrary, increases in alpha(1)
      adrenoceptors after 2-h withdrawal were seen in the nucleus accumbens core and
      retrosplenial cortex. In cocaine-sensitized rats, the density of alpha(1)
      adrenoceptors 2 h after the challenge with cocaine increased in the centrolateral
      amygdala, while in the granular retrosplenial cortex and in the most of thalamic
      nuclei, the densities of alpha(1)-adrenoceptors decreased. After 48-h withdrawal,
      the density of alpha(1)-adrenoceptors increased in the nucleus accumbens core and
      shell (by 21% and 58%, respectively), and in the amygdaloid centromedial and
      basolateral nuclei (by ca. 24%), while the decline was still observed in some
      thalamic nuclei. Our study shows for the first time that cocaine sensitization
      produces significant (dependent on the withdrawal time) alterations in the
      alpha(1)-adrenoceptor density, and the changes in some parts of the thalamus seem
      to be related to processes of cocaine relapses.

PMID- 17220541
TI  - Nicotine potentiates imipramine-induced effects on catecholamine metabolism:
      possible relation to antidepressant activity.
AB  - Following our behavioral studies demonstrating augmentation of imipramine action
      by concomitant administration of nicotine, we investigated the effects of one or
      14 days of treatment (twice daily) with imipramine and nicotine on dopamine
      metabolism in various brain areas of rat and noradrenaline in the brain stem. In
      addition, we evaluated the responses of this metabolism to apomorphine challenge
      in the rat. Generally, chronic treatment of imipramine and nicotine produced
      opposite effects to acute administration. As revealed by HPLC, dopamine
      metabolism in the nucleus accumbens was slightly decreased after 14 days of
      treatment with imipramine, and co-administration of nicotine resulted in a
      significant and much more pronounced depression of dopamine metabolism in all
      investigated dopaminergic structures. Such biochemical effects suggested the
      development of a compensatory mechanism related with hypersensitivity of dopamine
      D(2) receptors in the mesolimbic and nigrostriatal system. Chronic administration
      of imipramine produced an opposite effect to the acute one in the brain stem
      noradrenergic system, like it was observed in dopaminergic structures.
      Significant inhibition of noradrenaline metabolism after acute administration of
      imipramine may be explained by its inhibitory effect on noradrenaline reuptake
      process. In contrast, chronic imipramine administration had no effect on
      noradrenaline metabolism what indicated the development of subsensitivity of (2)
      adrenoceptors in the brain stem responsible for the rate of noradrenaline
      metabolism. Apomorphine alone decreased metabolism of both catecholamine,
      dopamine and noradrenaline through activation of dopamine D(2) receptors which
      are located also on noradrenergic neurons. The biochemical response to
      apomorphine in terms of dopamine metabolism was not changed by chronic
      administration of the investigated drugs but noradrenaline metabolism in the
      brain stem was strongly attenuated after a combined treatment of imipramine and
      nicotine. The present data demonstrate facilitation and potentiation of
      biochemical antidepressant-like effects of imipramine by nicotine co-treatment.
      We suggest that nicotine may potentiate the antidepressant-like effects of
      imipramine by promoting some plastic changes in the brain within dopamine and
      noradrenaline system considerably more strongly than imipramine alone.

PMID- 17220542
TI  - Neuroprotective effects of MTEP, a selective mGluR5 antagonists and neuropeptide
      Y on the kainate-induced toxicity in primary neuronal cultures.
AB  - The majority of studies on neuroprotection tested potentially protective
      compounds given before, simultaneously or shortly after damage. Such procedures
      are greatly different from the situation faced in clinical practice. In the
      present study, we tried to find out whether two compounds, a selective mGluR5
      antagonist 3-[(2-methyl-1, 3-thiazol-4-yl) ethynyl]-pyridine (MTEP) and neuro
      peptide Y (NPY) elicit neuroprotective action against excitotoxic damage in the
      mouse neocortical and hippocampal neuronal cultures after delayed treatment. In
      order to evoke toxic effects, primary cultures were exposed to 150 munic acid
      (KA) for 24 h (hippocampus) or for 48 h (neocortex). MTEP (1, 10 and 100 microM),
      or NPY (0.5 microM and 1 microM) were applied 30 min before, or 30 min, 1 h, 3 h
      or 6 h after KA. Kainate neurotoxicity was measured by lactate dehydrogenase
      (LDH) efflux from the damaged cells into the culture media. The results of our
      studies showed that MTEPor NPY treatment attenuated the kainate-induced LDH
      release in mouse neocortical and hippocampal cultures. The effect was observed
      when the compounds were added not only before, but also 30 min to 6 h after KA.
      Moreover, both MTEP and NPY displayed antiapoptotic activity as they prevented
      the KA-induced increase in the expression of caspase-3 activity in the cultures
      under study. Summing up, our data showed that MTEP and NPY were neuroprotective
      in wide time schedule. The effectiveness of late treatment with these compounds
      opens a new perspective for their potential therapeutic use.

PMID- 17220543
TI  - Frequency-dependent inhibition of antidromic hippocampal compound action
      potentials by anti-convulsants.
AB  - Using rat hippocampal slices, extracellularly recorded antidromic compound action
      potentials (cAP) were produced in CA1 pyramidal cell populations by electrical
      stimulation of the alveus at 0.5 Hz. These responses were additionally examined
      across a range of stimulus frequencies between 0.5 and 100 Hz. Anticonvulsant
      drugs in clinical use were applied via perfusion of the recording chamber. Three
      anticonvulsants produced a concentration-dependent inhibition of the cAP evoked
      at low frequency (0.5 Hz). The following IC(50) values were observed:
      lamotrigine, 210 microM (interpolated); carbamazepine, 210 microM (interpolated);
      phenytoin, 400 microM (extrapolated). The extent of inhibition produced was
      increased when trains of 30 cAPs were evoked at frequencies > or 30 Hz. This
      frequency dependence was quantified by measuring a response integral for a range
      of compound concentrations. Three other compounds valproate (5 mM), topiramate
      (500 microM) and levetiracetam (500 microM) produced no clear effect at any
      stimulus frequency tested. Using this simple neurophysiological assay it has been
      possible to compare the use-dependent inhibition of hippocampal action potentials
      by a range of anticonvulsants, providing a useful adjunct to patch clamp studies
      of such molecules at Na(+) channels. There is no clear correlation between the
      activity in this model and the clinical efficacy of these drugs in different
      forms of epilepsy.

PMID- 17220544
TI  - In vitro effects of CB1 receptor ligands on lipid peroxidation and antioxidant
      defense systems in the rat brain.
AB  - The in vitro effects of arachidonyl-2-chloroethylamide (ACEA; a selective CB(1)
      receptor agonist) and N-piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-cochlorophenyl)
      4-methyl-1H-pyrazole-3-carboxamide (SR141716A; a selective CB(1)-receptor
      antagonist) on lipid peroxidation (spontaneous and Fe (2+)-induced), total
      glutathione (GSH)-level and activity of antioxidant enzymes (superoxide
      dismutase, glutathione peroxidase and glutathione reductase) in the rat brain
      were studied. The effects of these CB(1)-induced), total glutathione (GSH)-level
      and activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase
      and glutathione reductase) in the rat brain were studied. The effects of these
      CB(1)-ligands in Fenton system (generating *OH radicals) were also examined. The
      cannabinoids did not change the total GSH-level and were without effects on the
      activity of antioxidant enzymes in the rat brain. These results proved a lack of
      in vitro pro-oxidant activity of the CB(1)-receptor ligands, as well as a lack of
      direct effects on GSH and enzyme molecules. ACEAand SR141716A were without effect
      on spontaneous lipid peroxidation, but decreased the Fe(2+)-induced brain lipid
      peroxidation and OH-provoked deoxyribose degradation in Fenton system. It can be
      suggested that the tested cannabinoids possess a metal-chelating activity, which
      might contribute to an antioxidant activity. The data, obtained in this study
      offer a background for investigation of the in vivo effects of these CB(1)
      receptor ligands on antioxidant defense systems in the brain of healthy animals
      and animals, previously subjected to oxidative stress.

PMID- 17220545
TI  - In vivo effects of CB1 receptor ligands on lipid peroxidation and antioxidant
      defense systems in the rat brain of healthy and ethanol-treated rats.
AB  - In vivo experiments were conducted to study the effects of N-(piperidin-l-yl)-5
      (4-chlorophenyl)-1-(2,4-cochlo-rophenyl)-4-methyl-1H-pyrazole-3-carboxamide
      (SR141716A; a potent and selective CB(1)-receptor antagonist) and ara-chidonyl-2
      chloroethylamide (ACEA; a selective CB(1)-receptor agonist) on spontaneous lipid
      peroxidation, glutathione (GSH) level and activities of antioxidant enzymes in
      rat tissues. Single doses of SR141716A(3 mg/kg, ip) and ACEA(10 mg/kg, ip) had no
      effect on all indices, studied in the brain, except for a decrease in GSH level
      by 10 mg/kg of SR141716A. The effects of repeated administration of the CB(1)
      receptor ligands (3 mg/kg, ip, once daily for 2 days) on the above indices in the
      brain and liver of control and ethanol-treated animals were also studied. Two
      weeks after ethanol exposure, the rats lost weight (by 41%), which correlated
      with their decreased water and food consumption (by 52% and 33%, respectively).
      The time of ethanol action was not sufficient to change the biochemical
      parameters in the brain, except for the lipid peroxidation. However, a decrease
      in GSH level and superoxide dismutase activity, as well as an increase in lipid
      peroxidation and glucose-6-phosphate dehydrogenase activity were registered in
      the liver. The repeated administration of CB(1) receptor ligands restored some of
      ethanol-induced changes. The present results suggested lack of pro-oxidant
      activity and potential antioxidant ability of the studied CB(1) receptor ligands,
      which might contribute to their beneficial effects.

PMID- 17220546
TI  - Cyclic AMP generating system in human microvascular endothelium is highly
      responsive to adrenaline.
AB  - We have tested cultured human microvascular endothelial cells (HMEC-1) for their
      ability to synthesize cyclic adenosine 3',5'-monophosphate (cAMP) in the absence
      or presence of various drugs. The accumulation of cAMP was only slightly affected
      by the addition of a phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine
      (IBMX) to the incubation medium. A direct stimulator of adenylyl cyclase
      forskolin and adrenergic drugs, such as adrenaline and noradrenaline, strongly
      increased cAMP accumulation in IBMX-treated HMEC-1 cells, whereas some other
      drugs known to stimulate the nucleotide synthesis in different cell/tissues were
      inactive (dopamine, histamine). Adrenaline was significantly more potent than
      noradrenaline. The effect of adrenaline on cyclic AMP production was reproduced
      by a selective beta-adrenoceptor agonist isoprenaline, antagonized by beta
      blocker propranolol, and was not influenced by both alpha(1) and alpha(2)
      selective antagonists, prazosin and yohimbine, respectively. Adrenaline did not
      significantly affect the ability of HMEC-1 cells to produce vascular endothelial
      growth factor (VEGF) or interleukin-8 (IL-8), the major angiogenic mediators. The
      results indicate that under basal (non-stimulated) conditions, the cAMP
      generating system of HMEC-1 cells maintained in culture remains rather quiescent,
      yet it can strongly respond to the hormone adrenaline acting on beta-adrenergic
      receptors.

PMID- 17220547
TI  - Effect of combined administration of ethanol and tiagabine on rabbit EEG.
AB  - Tiagabine is a new generation antiepileptic drug, a specific inhibitor of gamma
      aminobutiric acid (GABA) reuptake from the synaptic space to neurons and glia.
      Central effect of ethanol is mainly connected with its effect on GABAergic,
      glutamatergic, serotonergic and opioid transmission. The mechanism of tiagabine
      effect suggests that it may alleviate the rewarding effect of ethanol, which can
      be applied in the treatment of addiction. There are only a few studies discussing
      interactions of tiagabine and ethanol. In this study we have decided to examine
      interaction of ethanol with tiagabine by the use of pharmaco-EEG method. The
      influence of tiagabine on the effect of ethanol on EEG of rabbits (midbrain
      reticular formation, hippocampus, frontal cortex) was tested. Tiagabine was
      administered at a single dose (5 and 20 mg/kg) (po) or repeatedly twice a day at
      a total dose of 5 mg/kg for 14 days. Ethanol was injected (iv) at a dose of 0.8
      g/kg 60 min after tiagabine treatment. Ethanol caused an increase in the slow
      frequencies (0.5-4 Hz) in the recording, as well as a marked decrease of the
      fastest frequencies (30-45 and 13-30 Hz in cortex). Tiagabine leads to changes in
      rabbit EEG-recording suggesting their depressant-effect on the central nervous
      system (CNS) (increase in slow and decrease in fast frequencies). They are less
      pronounced after repeated doses, which may indicate the adaptative changes in the
      receptors. A single dose of tiagabine markedly increases the effect of ethanol on
      rabbit EEG, which indicates a synergistic inhibitory effect of these agents on
      the CNS. Repeated doses of tiagabine decrease the sensitivity of the hippocampus
      to the effect of ethanol, which may be important for the treatment of addictions.

PMID- 17220548
TI  - Involvement of PI3-K in neuroprotective effects of the 1,25-dihydroxyvitamin D3
      analogue - PRI-2191.
AB  - The active form of 1,25-dihydroxyvitamin D(3) prevents neuronal damage in vitro
      and in vivo , however, it induces also hypercalcemia and hyperphosphatemia. Side
      chain-modified analogues of 1,25-dihydroxyvitamin D(3), which show low calcemic
      activity, may be potentially useful in the treatment of some neurodegenerative
      diseases. Previously, we have found that PRI-2191 more potently than 1,25
      dihydroxyvitamin D(3) protects human neuroblastoma (SH-SY5Y) cells against
      hydrogen-peroxide-induced toxicity. In the present study, we evaluated effects of
      two other 1,25-dihydroxyvitamin D(3) analogues - PRI-1890 and PRI-1901 on the
      neuronal degeneration in the same cell model. In line with the previous study, 24
      h incubation with hydrogen peroxide (0.5 mM) was toxic to cells, as evidenced by
      an enhanced efflux of lactate dehydrogenase into the culture medium, and these
      effects were prevented by PRI-1890 and PRI-1901 at concentration of 5, 50 and 500
      nM. Comparing the neuroprotective effects of secosteroids, we found that all
      three analogues were efficient at lower concentration than 1,25-dihydroxyvitamin
      D(3) and among them the PRI-2191 showed the most evident concentration-dependent
      effect. In the second part of this study, an involvement of mitogen-activated
      protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3-K), kinases which
      play a crucial role in neurodegenerative processes, in neuroprotective action of
      1,25 dihydroxyvitamin D(3) and its the most potent analogue PRI-2191 has been
      investigated. The inhibitor of c-Jun N-terminal kinase (JNK)-MAPK (SP600125, 1
      microM), inhibitor of p38-MAPK (SB-203580, 1 and 10 microM) and inhibitor of
      extracellular signal-regulated kinase (ERK)-MAPK (PD-98059, 15 and 30 microM)
      attenuated the hydrogen peroxide-induced toxicity. Moreover, PD-98059 (30 microM)
      enhanced neuroprotective effects of 1,25 dihydroxyvitamin D(3) but not that of
      PRI-2191. In contrast, the inhibitor of PI3-K (wortmannin, 10, 100 nM) did not
      affect hydrogen peroxide-induced cell damage itself, however, it significantly
      antagonized the effect of PRI-2191. On the other hand, wortmannin did not affect
      the neuroprotective effects of 1,25 dihydroxyvitamin D(3) This suggests that the
      activation of PI3-K/Akt signaling pathway plays an important role in the
      mechanism of inhibitory action of PRI-2191 on hydrogen peroxide-evoked toxicity
      in SH-SY5Y cells. Furthermore, these data point to differential involvement of
      ERK-MAPK and PI3-K in neuroprotective effects of 1,25 dihydroxyvitamin D(3) and
      its low-calcemic analogue - PRI-2191.

PMID- 17220549
TI  - Effects of catecholamines on blood pressure in the femoral bone marrow cavity in
      ovariectomized rats.
AB  - Menopausal women display changes in the osseous tissue (osteoporosis, pathologic
      fractures) and disorders in the function of cardiovascular system (hypertension,
      cardiovascular disease, arteriosclerosis, calcification). Additionally,
      interdependence was observed between the loss of osseous tissue and disordered
      circulation, but the mechanism of the interdependence has never been fully
      recognized. In order to clarify this problem, the present study concentrated on
      the effects of catecholamines on blood pressure in the femoral bone marrow cavity
      in ovariectomized rats. The Ficat-Arlet method was used to examine blood pressure
      in marrow cavity. Norepinephrine, epinephrine, isoprenaline as well as
      adrenoceptor antagonists (phentolamine and propranolol) were administered to the
      controls and the ovariectomized rats. The examinations demonstrated that
      ovariectomized rats displayed decreased blood pressure in the marrow cavity. In
      addition, an intensified effect of catecholamines on blood pressure in the marrow
      cavity of osteoporotic bone in ovariectomized rats was observed.

PMID- 17220550
TI  - Effect of methylprednisolone treatment on expression of sPECAM-1 and CXCL10
      chemokine in serum of MS patients.
AB  - In order to elucidate the mechanism of intravenous methylprednisolone (IVMP)
      therapy of relapses in multiple sclerosis (MS) patients, we have undertaken a
      study on the expression of the chemokines: soluble platelet endothelial cell
      adhesion molecule (sPECAM-1) and interferon gamma-inducible protein (CXCL10),
      before and after treatment. As more becomes known about the mechanism of
      methylprednisolone (MP) action, it may be possible to find a more specific
      treatment as well for the individual patients as the phase of the disease. The
      mean level of sPECAM-1 in our material was almost identical in either the MS and
      control subjects. After a 5-day therapy with IVMP, no changes were found in
      comparison with the starting value. The serum concentration of CXCL10 in MS
      patients was found to be higher compared to that in sera from control subjects.
      After therapy with IVMP the mean level of CXCL10 was diminished to the initial
      value and occasionally was even lower than in the control group. The findings
      established in our present study indicate that IVMP diminished significantly the
      elevated expression of CXCL10, which seems to be an important factor in the
      mechanism of this drug action on MS relapses. It is important to stress that the
      reaction is not a general one because there was no effect on the expression of
      sPECAM-1.

PMID- 17220551
TI  - Neuraminidase inhibitors reduce nitric oxide production in influenza virus
      infected and gamma interferon-activated RAW 264.7 macrophages.
AB  - The influenza virus (influenza) infection causes an intense infiltration of
      pulmonary tissues by macrophages, which abundantly generate a free radical,
      nitric oxide (NO) resulting in lung damage. Neuraminidase inhibitors (NIs)
      restrict influenza virus replication but whether they can suppress NO production
      within macrophages is unknown. RAW 264.7 macrophages were exposed to interferon
      gamma (IFN-gamma), live influenza (A/PR/8/34) or a combination of both and were
      treated with NIs (oseltamivir or zanamivir). Results revealed that the drugs
      reduced a synergy between influenza and IFN-gamma in NO synthesis within the
      cells at all of the used concentrations (0.01, 0.1, 1 microg/ml). In contrast to
      zanamivir, this effect occurred in a concentration-dependent manner with
      oseltamivir treatment. On the other hand, all concentrations of zanamivir
      significantly suppressed NO production in comparison to that upon the combined
      exposure only (p < 0.05). Both compounds also considerably decreased NO
      generation in the IFN-gamma-stimulated macrophages, and zanamivir in the
      influenza-infected cells as well. However, neither of the drugs inhibited iNOS
      mRNA expression in the cells containing these stimulants. Additionally, the data
      indicate that a prodrug oseltamivir can be activated in vitro within the
      macrophage cultures. These findings are important for designing treatment
      approaches to limit pulmonary inflammation during influenza infection.

PMID- 17220552
TI  - Operant self-administration of ethanol in Warsaw high-preferring (WHP) and Warsaw
      low-preferring (WLP) lines of rats.
AB  - The results of the present experiment demonstrate that ethanol-preferring line of
      rats (WHP), and ethanol-nonpreferring line of rats (WLP) are able to acquire and
      maintain lever pressing reinforced by EtOH (oral operant EtOH self
      administration) under FR-1 and FR-2 schedule of reinforcement. On the other hand,
      WHP rats but not WLP rats, displayed the high ability to acquire and maintain
      robust lever pressing for EtOH under FR-3 procedure. These data suggest that EtOH
      possesses stronger reinforcing properties in WHP rats. Nevertheless, WLP rats are
      able to acquire operant self-administration of EtOH when response demand of the
      reinforcement schedule is lower. Thus, both lines of rats can differ
      substantially in the amount of EtOH intake when its access is continuous and
      freely available, but less fundamentally when they respond for EtOH reward under
      low-demand schedules of partial reinforcement.

PMID- 17220553
TI  - Anticonvulsant and antidepressant activity of the selected terpene GABA
      derivatives in experimental tests in mice.
AB  - The present study was designed to investigate the central nervous system activity
      of terpene GABA (and piracetam) derivatives designated as BF-1, BF-2, BF-3, BF-4,
      BF-5, BF-6. We assessed their anticonvulsant activity in the two main mouse
      models of seizures (MES-test, PTZ-test), an antidepressant-like effect in the
      forced swim test (FST), as well as an influence on spontaneous locomotor
      activity. Our study demonstrated the strong anticonvulsant activity of (1S,3R,7R)
      (-)-3,8,8-trimethyl-4-aza-bicyclo[5.1.0]acetate-5-one hydrochloride (compound BF
      2) in the PTZ-test. Activity of BF-2 was equipotent to ethosuximide (380 mg/kg,
      po) in the PTZ-test, when used at a dose of 100 mg/kg, po. No neurotoxic effects
      were demonstrated by administration of all tested compounds. Moreover, BF-2, BF
      3, BF-6 compounds significantly reduced the immobility time in FST at both doses
      (by 21-50%), while BF-5 induced a significant anti-immobility effect only when
      used at a dose of 100 mg/kg (by 39%). The compound BF-6 used at the dose of 30
      mg/kg was the most active (50% reduction), and the effect was similar to the
      result obtained with classical antidepressant--imipramine. The motor stimulatory
      activity was demonstrated by BF-1 compound at the dose of 100 mg/kg with no
      effect at a lower (30 mg/kg) dose. On the other hand, the BF-3 at 30 mg/kg
      significantly decreased spontaneous activity during 30 min observation period,
      while no alteration in this activity during 6-min observation was detected. At
      present, it is not possible to indicate which mechanisms of novel, active terpene
      GABA derivatives are involved in the demonstrated antidepressant-like activity.
      Although further studies are needed to solve this issue, these data suggest a
      potential value of the examined terpene GABA derivatives.

PMID- 17220554
TI  - Gabapentin synergistically interacts with topiramate in the mouse maximal
      electroshock seizure model: an isobolographic analysis.
AB  - The anticonvulsant effects produced by topiramate (TPM) and gabapentin (GBP)--two
      second-generation antiepileptic drugs, in numerous fixed-ratio combinations of
      8:1, 4:1, 2:1, 1:1, 1:2, 1:4 and 1:8 were examined by isobolographic analysis in
      the mouse maximal electroshock seizure (MES) model. Results indicate that the
      combinations of TPM and GBP at the fixed-ratios of 2:1, 1:1, 1:2, 1:4 and 1:8
      resulted in supra-additive (synergistic) interaction against MES-induced
      seizures. Moreover, the combinations of TPM and GBP (at their median effective
      doses) did not affect motor performance of animals challenged with the chimney
      test and had no impact on neuromuscular tone in the grip-strength test.
      Additionally, GBP had no impact on total brain TPM concentrations, and
      simultaneously, TPM did not alter brain GBP concentrations, indicating that the
      interaction between drugs was pharmacodynamic in nature. In conclusion, supra
      additive interaction of TPM with GBP against MES-induced seizures, lack of motor
      coordination and neuromuscular tone impairments as well as lack of
      pharmacokinetic interactions between TPM and GBP in preclinical study, strongly
      support the combined application of both antiepileptic drugs in patients with
      refractory partial epilepsy.

PMID- 17220555
TI  - Influence of NG-nitro-L-arginine on the anticonvulsant and acute adverse effects
      of some newer antiepileptic drugs in the maximal electroshock-induced seizures
      and chimney test in mice.
AB  - Overwhelming evidence indicates that nitric oxide (NO) plays an important role in
      epileptogenesis and seizure activity in the brain. The results of experimental
      studies on animals provide, however, discrepant information reporting that NO has
      both anti- and pro-convulsant action in the brain. The objective of this study
      was to determine the effect of N(G)-nitro-L-arginine (L-NA--a non-specific NO
      synthase inhibitor) on the anticonvulsant and acute adverse-effect profiles of
      four second-generation antiepileptic drugs (felbamate [FBM], lamotrigine [LTG],
      oxcarbazepine [OXC] and topiramate [TPM]) in the maximal electroshock (MES)
      induced seizure model and the chimney test in mice. Results indicated that L
      NA(at 40 mg/kg, ip) did not affect significantly the antiseizure activity of all
      examined drugs. However, the antielectroshock action of FBM and LTG after co
      administration of L-NA was attenuated by 36% and 28%. In contrast, the
      anticonvulsant effects of TPM and OXC were almost unchanged after L-NA
      administration. Moreover, the NO synthase inhibitor (40 mg/kg, ip) did not
      enhance the acute adverse-effect profiles of the studied antiepileptic drugs in
      the chimney test. In conclusion, the observed reduction of the anticonvulsant
      effects of FBM and LTG after co-administration of L-NA may suggest a pro
      convulsant activity of L-NA and the cooperation of NO with the antiseizure
      properties of FBM and LTG in the MES test in mice.

PMID- 17220556
TI  - Antinociceptive effect of lidocaine in rats.
AB  - Lidocaine, a local anesthetic drug, exerts its effect by blocking sodium channels
      in peripheral sensory neurons. It is commonly used in clinical practice as a
      local anesthetic drug. This study was undertaken in order to determine the effect
      of lidocaine on sodium channels in neurons of the central nervous system and its
      modulatory effect on the pain perception in rats. Therefore, the effect of direct
      lidocaine administration icv on pain perception in rats exposed to noxious
      thermal stimuli was determined. A significant long-lasting antinociceptive effect
      of lidocaine injected at the doses ranging between 0.065-1.3 micromol (17.5-351
      microg, respectively) was documented. It was concluded that intracerebral
      administration of sodium channel blockers might be a useful method in the study
      of pain perception in the brain.

PMID- 17220557
TI  - Amifostine improves hemodynamic parameters in doxorubicin-pretreated rabbits.
AB  - Amifostine reduces nephrotoxicity and myelotoxicity of alkylating agents. Little
      is known about its role in preventing cardiotoxicity. We studied if amifostine
      could affect the hemodynamic parameters in doxorubicin-pretreated rabbits. The
      animals were divided into six groups consisting of 6 rabbits each. Group 1-
      doxorubicin iv 2 mg/kg of body weight 4 times every 14 days (cumulative dose 8
      mg/kg); group 2--a dose of doxorubicin was 3 mg/kg (cumulative dose 12 mg/kg);
      groups 3 and 4--amifostine iv 30 mg/kg 15 min prior to doxorubicin 2 and 3 mg/kg,
      respectively, groups 5 and 6--amifostine- and physiological saline-treated
      controls. Two-three weeks after the last dose the animals were anesthetized and
      cardiac index (CI) i.e. cardiac output/body weight, and total peripheral
      resistance (TPR) were calculated using the method of human I(125) albumin
      dilution. Mean CI was 71.4 +/- 40.5 ml/min/kg in group 2, 135.8 +/- 41.2 in group
      5 (p < 0.001), and 116.4 +/- 47.8 in group 6 (p < 0.001), TPR was 4.7 +/- 3.3 kPa
      x s/l, 1.1 +/- 1.2 (p < 0.001), and 1.9 +/- 1.1 (p < 0.001), respectively. In
      group 4, CI was 135.4 +/- 33.2, and TPR was 1.1 +/- 0.6. The differences in CI
      and TPR between groups 2 and 4 were statistically significant (p < 0.001). In
      conclusion, pretreatment with doxorubicin at the total dose of 12 mg/kg
      significantly reduced CI and increased TPR. Amifostine improved CI and TPR in
      doxorubicin-pretreated rabbits.

PMID- 17220558
TI  - Thiopurine S-methyltransferase phenotype-genotype correlation in hemodialyzed
      patients.
AB  - Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme, catalyzing S
      methylation of thiopurine drugs. TPMT exhibits autosomal codominant polymorphism.
      Patients carrying a variant genotype have low TPMT activity, and produce elevated
      levels of 6-thioguanine nucleotides (6-TGN) in their red blood cells (RBC). 6-TGN
      accumulation may result in azathioprine (AZA)-induced bone marrow
      myelosuppression in the course of treatment with the drug in a standard dosage
      regimen in patients following renal transplantation. In the current study, TPMT
      activity (phenotype) and genotype were determined in dialyzed patients, qualified
      for renal transplantation. TPMT activity was measured in RBC after dialysis by
      HPLC method. Patients were genotyped for TPMT *2, *3A and *3C variant alleles
      using PCR-RFLP and allele-specific PCR methods. TPMT activity ranged between 12.2
      and 45.5 nmol 6-mMP/g Hb/h (median value 30.6). A significant correlation between
      TPMTphenotype and genotype was noted: the heterozygous patients (11.5%)
      demonstrated significantly lower mean TPMT activity as compared to the wild
      homozygotes (17 +/- 3.6 vs. 32.4 +/- 4.8 nmol 6-mMP/g Hb/h, p < 0.0003). No
      overlap in TPMT activity values between the group of heterozygous (range 12.2
      20.6) and wild-type homozygous patients (range 22.7-45.5) was noted. TPMT
      activity, established after hemodialysis and TPMT genotyping results seem to be
      convergent in dialyzed patients, so both methods can be used for the
      identification of patients with lower TPMT activity. Such tests could be helpful
      in AZA dose individualization, and thus in reducing the risk of myelosuppression
      during AZA therapy following renal transplantation.

PMID- 17220559
TI  - Effect of mirtazapine on the CYP2D activity in the primary culture of rat
      hepatocytes.
AB  - Our previous studies carried out on rats showed that mirtazapine given
      intraperitoneally at a dose of 3 mg/kg, twice a day for two weeks, increased the
      activity of CYP2D measured as ethylmorphine O-deethylation in liver microsomes.
      The aim of the present work was to find out whether the mirtazapine-induced
      increase in the CYP2D activity observed in vivo is connected with the central
      action of mirtazapine or the drug acts directly on hepatocytes. For this purpose,
      we studied the influence of pharmacological concentrations of mirtazapine (0.1,
      1.0, 10 microM for 96 h) on the activity of CYP2D measured as the rates of
      ethylmorphine O-deethylation and dextromethorphan O-demethylation in the primary
      culture of rat hepatocytes. Additionally, we tested the ability of CYP isoforms
      to catalyze ethylmorphine O-deethylation, using cDNA-expressed CYPs and CYP
      inhibitors applied to liver microsomes. The obtained results indicate that
      mirtazapine applied at pharmacological concentrations can moderately increase the
      activity of rat CYP2D in hepatocytes, and CYP2D2 isoform contributes mostly to
      this effect. Similar result was previously obtained after in vivo administered
      mirtazapine in liver microsomes, but not in brain microsomes, the latter
      containing mainly CYP2D4 isoform. Mirtazapine appears to act directly on
      hepatocytes and its effect does not seem to depend on the central pharmacological
      action of the antidepressant. CYP2D2 is the main isoform catalyzing ethylmorphine
      O-deethylation while CYP2A2, CYP2C6 and CYP2C11 are of minor importance.

PMID- 17220560
TI  - Nuclear receptor-mediated transcriptional regulation in Phase I, II, and III
      xenobiotic metabolizing systems.
AB  - Studies of the genetic regulation involved in drug metabolizing enzymes and drug
      transporters are of great interest to understand the molecular mechanisms of drug
      response and toxic events. Recent reports have revealed that hydrophobic ligands
      and several nuclear receptors are involved in the induction or down-regulation of
      various enzymes and transporters involved in Phase I, II, and III xenobiotic
      metabolizing systems. Nuclear receptors (NRs) form a family of ligand-activated
      transcription factors (TFs). These proteins modulate the regulation of target
      genes by contacting their promoter or enhancer sequences at specific recognition
      sites. These target genes include metabolizing enzymes such as cytochrome P450s
      (CYPs), transporters, and NRs. Thus it was now recognized that these NRs play
      essential role in sensing processing xenobiotic substances including drugs,
      environmental chemical pollutants and nutritional ingredients. From literature,
      we picked up target genes of each NR in xenobiotic response systems. Possible
      cross-talk, by which xenobiotics may exert undesirable effects, was listed. For
      example, the role of NRs was comprehensively drawn up in cholesterol and bile
      acid homeostasis in human hepatocyte. Summarizing current states of related
      research, especially for in silico response element search, we tried to elucidate
      nuclear receptor mediated xenobiotic processing loops and direct future research.

PMID- 17220561
TI  - Histogram analysis of pharmacokinetic parameters by bootstrap resampling from one
      point sampling data in animal experiments.
AB  - A bootstrap method is proposed for assessing statistical histograms of
      pharmacokinetic parameters (AUC, MRT, CL and V(ss)) from one-point sampling data
      in animal experiments. A computer program, MOMENT(BS), written in Visual Basic on
      Microsoft Excel, was developed for the bootstrap calculation and the construction
      of histograms. MOMENT(BS) was applied to one-point sampling data of the blood
      concentration of three physiologically active proteins ((111)In labeled Hsp70,
      Suc(20)-BSA and Suc(40)-BSA) administered in different doses to mice. The
      histograms of AUC, MRT, CL and V(ss) were close to a normal (Gaussian)
      distribution with the bootstrap resampling number (200), or more, considering the
      skewness and kurtosis of the histograms. A good agreement of means and SD was
      obtained between the bootstrap and Bailer's approaches. The hypothesis test based
      on the normal distribution clearly demonstrated that the disposition of (111)In
      Hsp70 and Suc(20)-BSA was almost independent of dose, whereas that of (111)In
      Suc(40)-BSA was definitely dose-dependent. In conclusion, the bootstrap method
      was found to be an efficient method for assessing the histogram of
      pharmacokinetic parameters of blood or tissue disposition data by one-point
      sampling.

PMID- 17220562
TI  - Evaluation of human CYP1A2 and CYP3A4 mRNA expression in hepatocytes from
      chimeric mice with humanized liver.
AB  - We investigated and compared the expression of human CYPs mRNA in primary
      cultures of cryopreserved human hepatocytes and in chimeric mice constructed by
      transplanting hepatocytes from the same human donors. Analysis was performed by
      real-time reverse-transcription polymerase chain reaction. Initial expression
      levels for the 12 human CYPs mRNA in chimeric mouse hepatocytes were higher than
      those in human hepatocytes, but a low correlation coefficient was observed
      (r=0.690). After 24 h of culture, the correlation remained low (r=0.699). The
      medium was replaced with fresh medium without human epidermal growth factor, and
      after 48 h of culture, expression of the 12 human CYPs mRNA were very similar in
      human hepatocytes and chimeric mouse hepatocytes, and a higher correlation
      coefficient was observed (r=0.809). After 72 h of culture, the correlation
      remained high (r=0.873). The ratio of human CYP1A2 mRNA to beta-actin mRNA in
      chimeric mouse hepatocytes decreased quickly during the first 24 h of culture,
      and then remained constant. Expression profiles of human CYP1A2 mRNA in chimeric
      mouse hepatocytes were similar to those in human hepatocytes after exposure of
      beta-naphthoflavone. CYP3A4 mRNA expression was increased significantly by
      rifampicin (Rif) exposure in human hepatocytes, whereas Rif-induced increases in
      CYP3A4 mRNA expression in chimeric mouse hepatocytes was seen for two of the
      three donors. In conclusion, we demonstrated that expression and induction of
      human CYPs in human hepatocytes can be reproduced in chimeric mouse hepatocytes.

PMID- 17220563
TI  - In vivo evaluation of coumarin and nicotine as probe drugs to predict the
      metabolic capacity of CYP2A6 due to genetic polymorphism in Thais.
AB  - The association between the distribution characteristics of CYP2A6 catalytic
      activities toward nicotine and coumarin, and the frequency distribution of CYP2A6
      variant alleles reported was estimated in 120 healthy Thais. The distributions of
      the subjects as classified by the amounts of 7-hydroxycoumarin (7-OHC) excreted
      in the urine and by cotinine/nicotine ratio in the plasma were clearly bimodal.
      However, the numbers of apparently poor metabolizers for coumarin and nicotine
      were different. The inter-individual variability in the in vivo dispositions of
      coumarin and nicotine closely related to the CYP2A6 genetic polymorphism. There
      was a close correlation between the rate of 7-OHC excretion in the urine and
      cotinine/nicotine ratio in the plasma among subjects (R=0.92, p<0.001). The
      frequency of CYP2A6 allele found in the present study was: CYP2A6*1A=32% (95% CI,
      22.1-39.4%), CYP2A6*1B=27% (95% CI, 19.4-33.5%), CYP2A6*9=20% (95% CI, 17.6
      23.3%), CYP2A6*4=14% (95% CI, 9.6-17.8%), CYP2A6*7=5% (95% CI, 3.7-9.4%),
      CYP2A6*10=2% (95% CI, 0.8-5.1%). Subjects having CYP2A6*1A/*1B were found to have
      a higher rate of 7-OHC excretion, as well as a higher cotinine/nicotine ratio in
      the plasma compared with those of the other genotypes. In contrast, subjects with
      CYP2A6*4/*7 and CYP2A6*7/*7 almost lacked any cotinine formation, whereas urinary
      7-OHC was still detectable. CYP2A6*9 allele clearly resulted in reduced enzyme
      activities. Despite the absence of the homozygote for CYP2A6*10 allele, the
      presence of CYP2A6*10 allele significantly decreased the enzyme activities. The
      results of the present study demonstrate that in vivo phenotyping of CYP2A6 using
      nicotine and coumarin are not metabolically equivalent. Nicotine is a better
      probe according to its specificity, while coumarin is still valuable to be used
      for a routine CYP2A6 phenotyping since the test employs a non-invasive method.

PMID- 17220564
TI  - In vivo-in vitro relationship of methotrexate 7-hydroxylation by aldehyde oxidase
      in four different strain rats.
AB  - The in vivo metabolism of methotrexate (MTX) to 7-hydroxymethotrexate (7-OH-MTX)
      was studied using four strains of rats. When MTX was administered to these rats,
      7-OH-MTX was detected as the major in vivo metabolite, mainly in bile and feces,
      and also slightly in the urine. There were marked strain differences in the
      amounts of 7-OH-MTX excreted in bile, feces and urine. The highest recovery of 7
      OH-MTX in bile, feces and urine was observed in Sea:SD rats (6.2%, 4.2% and 0.8%
      of dose, respectively), followed by Jcl:SD and Crj:SD rats. The lowest recovery
      (0.02%, 0.2% and 0.003%, respectively) was observed in WKA/Sea rats. The
      variations of excreted amount of 7-OH-MTX were closely correlated with the strain
      differences of cytosolic MTX 7-hydroxylase and benzaldehyde oxidase activities.
      Our results indicate that variation of formation of 7-OH-MTX from MTX in vivo in
      rats is due primarily to variation of aldehyde oxidase.

PMID- 17220565
TI  - Temporal decline in sirolimus elimination immediately after pancreatic islet
      transplantation.
AB  - Pancreatic islet transplantation is a curable treatment for type 1 diabetes and
      has been put into practice in various countries. In this study, we analyzed the
      pharmacokinetic characteristics of sirolimus and tacrolimus in six Japanese
      patients with pancreatic islet transplants immediately after surgery, and
      monitored efficacy and toxicity. The patients were treated with immunosuppressive
      therapy based on the Edmonton protocol, that is, sirolimus and low-dose
      tacrolimus. Pharmacokinetic analyses were performed using the nonlinear mixed
      effects modeling program NONMEM. Large inter- and intra-individual variability
      was observed in the pharmacokinetics of sirolimus and tacrolimus. A model with
      increased apparent clearance in the postoperative period explained well the intra
      individual variability in the pharmacokinetics of both drugs. The most frequent
      drug-induced toxicity was a decrease in the white blood cell count, and two of
      six patients required the administration of granulocyte colony-stimulating
      factor. Clinical laboratory tests immediately before the transplantation and
      cytochrome P450 3A5 genotype were not related to the high blood concentrations of
      sirolimus after the loading dose. From these results, the apparent clearance of
      sirolimus and tacrolimus might temporally decline immediately after pancreatic
      islet transplantation. A high trough concentration of sirolimus might increase
      the risk of hematological toxicy, and adjustment of the dosage for
      immunosuppressive treatment will be necessary in Japanese patients.

PMID- 17220566
TI  - Effect of amiodarone on the serum concentration/dose ratio of metoprolol in
      patients with cardiac arrhythmia.
AB  - Amiodarone has pharmacokinetic interactions with a number of therapeutic drugs,
      including warfarin, phenytoin, flecainide, and cyclosporine. Metoprolol is mainly
      metabolized by CYP2D6, and desethylamiodarone, a metabolite of amiodarone, has a
      markedly greater inhibitory effect on CYP2D6 than amiodarone. Therefore, the goal
      of this study was to evaluate the effect of amiodarone and desethylamiodarone on
      the serum concentration/dose ratio (C/D) of metoprolol in 120 inpatients with
      cardiac arrhythmias that received either metoprolol and amiodarone (MET+AMD
      group, n=30) or metoprolol alone (MET group, n=90). The ratio of administered
      metoprolol was compared between the MET and the MET+AMD groups. The dose of
      metoprolol and patient age were significantly higher in the MET group when
      compared with the MET+AMD group (1.00+/-0.480 versus 0.767+/-0.418 mg/kg/day,
      p<0.050; 68.6+/-10.6 versus 57.6+/-14.1 years, p<0.001, respectively), but the
      C/D ratio was significantly lower in the MET group than in the MET+AMD group
      (90.8+/-64.0 versus 136+/-97.8, p<0.01). Furthermore, a significant correlation
      was found between the C/D ratio and desethylamiodarone concentration (n=30,
      r=0.371, p<0.01). The results suggest that there is a significant interaction
      between amiodarone and metoprolol via desethylamiodarone-induced inhibition of
      CYP2D6. Therefore, careful monitoring of metoprolol concentrations/bioactivity of
      CYP2D6 is required in the context of co-administration of amiodarone and
      metoprolol.

PMID- 17220567
TI  - Allele and genotype frequency of MDR1 C3435T in Tamilian population.
AB  - The allele and genotype frequencies of MDR1 C3435T polymorphism were determined
      in 185 unrelated healthy Tamilians. The genomic DNA was extracted from peripheral
      leucocytes using phenol chloroform method and genotyped by PCR-RFLP method. The
      frequencies of MDR1 C3435 and T3435 alleles in Tamilian population were 0.46 and
      0.54 respectively. The distribution of T3435 in this population was found to be
      greater than Africans and almost similar to Caucasians and Orientals. The
      distribution of CC, CT and TT genotypes was 0.18, 0.56 and 0.26 respectively. The
      frequency distribution of the CC genotype was lower in them when compared with
      Chinese and Africans whereas CT genotype was higher in comparison with all the
      major ethnic groups.

PMID- 17220568
TI  - Fourteen novel genetic variations and haplotype structures of the TYMS gene
      encoding human thymidylate synthase (TS).
AB  - Forty genetic variations including 14 novel ones were found in the human TYMS
      gene, which encodes thymidylate synthase, in 263 Japanese cancer patients who
      received 5-fluorouracil (FU)-based chemotherapy. Three novel variations were
      located within the 28-bp tandem repeat sequence in the 5'-untranslated region
      (UTR) and were designated 5Rc, 3Rc-ins and 4Rc. Allele frequencies were 0.021 for
      5Rc, 0.006 for 3Rc-ins and 0.002 for 4Rc. Other novel variations included -133G>C
      and -125G>C in the 5'-UTR; IVS1-278G>A, IVS2-68C>T, IVS2-23T>C,
      IVS4+122_+123insATTG, IVS4-141G>A, IVS5-100A>T and IVS6-111G>A in the introns;
      and 1244(*302)A>G and 1264(*322)G>A in the 3'-UTR. The allele frequencies were
      0.34 for IVS4+122_+123insATTG, 0.042 for -133G>C, 0.011 for IVS4-141G>A, 0.006
      for -125G>C, 0.004 for IVS1-278G>A, IVS2-68C>T, 1244(*302)A>G and 1264(*322)G>A,
      and 0.002 for IVS2-23T>C, IVS5-100A>T and IVS6-111G>A. Using the detected
      polymorphisms, linkage disequilibrium (LD) analysis was performed, which divided
      the TYMS gene into three LD blocks. The 28-bp tandem repeat sequence in the 5'
      UTR was assigned as Block 2 with a total of 7 alleles. In Blocks 1 and 3, 7 and
      19 haplotypes were determined/inferred, respectively. Our findings provide
      fundamental and useful information for genotyping TYMS in the Japanese and
      probably other Asian populations.

PMID- 17220569
TI  - [Animal experiments recommended by the Japanese Pharmacological Society
      (evaluation and decrease of pain): introduction and new guidelines for animal
      experiments for the Japanese Pharmacological Society].

PMID- 17220570
TI  - [Pharmacology of pain].

PMID- 17220571
TI  - [Assessment and criteria of pain, distress, and euthanasia].

PMID- 17220572
TI  - [Animal experiment ethics committee of Showa University].

PMID- 17220573
TI  - [Inspection of laboratory animal facilities].

PMID- 17220574
TI  - [Recent and potential drugs for treatment of insomnia].

PMID- 17220575
TI  - [Pharmacotherapy of insomnia in clinical medicine].

PMID- 17220576
TI  - [Perspectives on genome-based drug discovery].

PMID- 17220577
TI  - [Current status, problems, and future directions of bioinformatics for drug
      discovery].

PMID- 17220578
TI  - Visualization of antigen-specific T cell in living arthritic mice.

PMID- 17220579
TI  - Myelodysplastic syndromes: recent progress in diagnosis and understanding of
      their pathophysiology.
AB  - Myelodysplastic syndromes (MDS) are common malignant disorders with a poor
      prognosis. MDS are a group of highly heterogeneous disorders but show certain
      universal findings including a high incidence in the elderly population,
      cytopenia, dysplastic myeloid cells, and frequent transformation to acute myeloid
      leukemia. Until recently, the vast majority of MDS patients were treated with
      supportive therapy alone, such as transfusions. Allogeneic stem cell
      transplantation (SCT) has the potential for cure, although due to the age and
      comorbidity of MDS patients, the role of allogeneic SCT in MDS has been limited.
      Recently, research in MDS has shown substantial advances that have deepened our
      understanding of MDS pathophysiology and changed our approach to MDS patients.
      This review touches on some recent developments in the diagnosis and
      pathophysiology of MDS.

PMID- 17220580
TI  - Cyclo-oxygenase-2 over-expression is associated with human esophageal squamous
      cell carcinoma.
AB  - Cyclo-oxygenase (COX)-2 is not usually detectable in normal tissues but is
      induced in inflammation and carcinogenesis. The level of COX-2 is elevated in
      cancer tissues of the colon, bladder, and skin. In the esophagus, squamous cell
      carcinoma and adenocarcinoma are known to express COX-2. The purpose of this
      study was to clarify the association of COX-2 expression with clinicopathological
      factors of squamous cell carcinoma. The immunohistochemical expression of COX-2
      was examined in 48 surgical specimens of esophageal squamous cell carcinoma.
      Although COX-2 over-expression was more frequently observed in tumors invading
      the submucosa (T1b, 76.4%), muscularis propria (T2, 57.1%), adventitia, or
      adjacent organs (T3 approximately 4, 83.3%), even 33.3% of mucosal cancers, such
      as T1a, showed COX-2 over-expression. COX-2 over-expression was present in 82.3%
      of lymph node-negative patients but in only 54.8% of lymph node positive
      patients. There was no difference in COX-2 over-expression between the earlier
      stages (0 and I, 60%) and more advanced stages (II approximately IV, 69.6%). COX
      2 over-expression did not correlate with survival during 3 years of follow-up.
      These findings suggest that COX-2 is associated with the phenotype of the
      esophageal squamous cell carcinoma cells, including superficial cancer cells, and
      may be related to tumor growth in esophageal squamous cell carcinoma.

PMID- 17220581
TI  - Analysis of risk factors for postpneumonectomy bronchopleural fistulas in
      patients with lung cancer.
AB  - BACKGROUND: Bronchopleural fistula is a potentially fatal complication of
      pulmonary resections, especially pneumonectomy. METHODS: Univariate and
      multivariate analyses of the development of bronchopleural fistula were performed
      in 12 patients with bronchopleural fistula and 102 patients without
      bronchopleural fistula who had undergone pneumonectomy from January 1983 through
      December 2005. RESULTS: Bronchopleural fistula developed after pneumonectomy in
      12 patients (8.5%). Seven (58.7%) of the 12 patients died of bronchopleural
      fistula. Univariate analysis showed that preoperative infection, right
      pneumonectomy, and pathological N2, 3 disease significantly contributed to the
      development of postpneumonectomy bronchopleural fistula (p=0.0002, p=0.0043, and
      p=0.0387, respectively). Multivariate analysis also showed that preoperative
      infection, right pneumonectomy, and pathological N2, 3 disease were significant
      risk factors for postpneumonectomy bronchopleural fistula. CONCLUSIONS:
      Bronchopleural fistula is strongly associated with preoperative infection, right
      pneumonectomy, and pathological N2, 3 disease. Bronchial stump coverage with
      pedicled tissue flaps and preservation of the bronchial arteries during
      mediastinal lymph node dissection are recommended to maintain the blood supply to
      the bronchial stump in patients at risk.

PMID- 17220582
TI  - Video-assisted breast surgery: reconstruction after resection of more than 33% of
      the breast.
AB  - BACKGROUND: Improvements in reconstructive mammoplasty methods have made it
      possible to resect more of the mammary gland while achieving good esthetic
      results in breast-conserving surgery. We report the esthetic results of extended
      wide resection of the breast with reconstruction procedures. METHODS: Breast
      conserving surgery was performed using a video-assisted breast surgery (VABS)
      technique. Breast reconstruction was simultaneously performed using the following
      three methods: mobilization of the remnant mammary gland, transplantation of the
      lateral tissue flap, and filling with an absorbent synthetic fiber mesh or
      cotton. The cosmetic results were evaluated with an original five-item-by-four
      step scoring system: ABNSW-assessing asymmetry, breast shape, nipple shape, skin
      condition, and wound scar. RESULTS: From December 2001 through March 2006, we
      performed endoscopic VABS in 130 patients with breast diseases. The candidates
      were 29 patients with breast cancer who required resection of more than 33% of
      the mammary gland because of ductal carcinoma in situ (1 patient), multiple
      cancers (6 patients), widely extended lesions (20 patients), and lesions after
      preoperative systemic therapy (2 patients). Twenty-one patients underwent
      resection of 33% to 50% of the breast, and 8 underwent resection of more than 50%
      of the breast. All surgical margins were negative on examination of permanent
      histological preparations. The original shape of the breast was preserved. There
      was no local recurrence after follow-up times of 33 months (maximum) and 19
      months (average). CONCLUSIONS: The newly devised reconstruction methods with VABS
      can markedly increase the mammary gland resection volume while achieving a good
      esthetic outcome, ensuring a precise disease-free surgical margin, and expanding
      the indications for breast-conserving therapy.

PMID- 17220583
TI  - Two cases of subacute combined degeneration: magnetic resonance findings.
AB  - We report two cases of subacute combined degeneration. Both patients had
      undergone total gastrectomy. The chief complaints were numbness in both upper
      extremities in case 1 and numbness in both the upper and lower extremities and
      gait disturbance in case 2. The pain, temperature, and vibration senses of both
      patients were decreased. Laboratory examinations showed macrocytic anemia and a
      decreased serum vitamin B12 level in both cases. In both cases T2-weighted
      magnetic resonance images showed an area of hyperintensity in the dorsal columns
      of the cervical spinal cord. The patients were treated with vitamin B12. The
      abnormal signals had disappeared on follow-up magnetic resonance examination 1
      year later in case 1 and 3 months later in case 2. These patients showed
      neurological improvement, but the numbness in the upper extremities persisted
      even after the area of abnormal signal intensity had disappeared in case 1.

PMID- 17220584
TI  - Does a bone deformity of the distal phalanx undergo remodeling after removal of a
      congenital ectopic nail?: A case with periodic radiographic follow-up.
AB  - BACKGROUND: Congenital ectopic nails are rare and are characterized by the
      presence of nail-like tissue mainly at the tip of a finger or toe. OBJECTIVE:
      Although the accompanying bone deformity might undergo remodeling after removal
      of the ectopic nail, it remains unknown whether complete bone remodeling can be
      eventually achieved, and whether such remodeling is necessary to improve the
      final cosmetic appearance of the concerned fingertip. METHODS AND RESULTS: Follow
      up with periodic radiographic examination for 1 year after surgery in a child
      with congenital ectopic nail revealed no bone remodeling, despite the
      satisfactory cosmetic result. CONCLUSION: We conclude that residual bone
      deformity does not affect the final appearance.

PMID- 17220585
TI  - Computed tomography-guided mediastinal drainage for iatrogenic perforation of the
      esophagus.
AB  - We report a case of perforation of the esophagus associated with mediastinitis
      and pneumomediastinum during endoscopic treatment. The patient was successfully
      treated by means of nonsurgical computed tomography-guided mediastinal drainage.
      Esophagoscopy demonstrated a scar on the 14th day at the perforation site. This
      nonsurgical treatment with computed tomography-guided mediastinal drainage is
      proposed as a less invasive treatment for iatrogenic perforation of the
      esophagus.

PMID- 17220586
TI  - Boerhaave syndrome treated conservatively following early endoscopic diagnosis: a
      case report.
AB  - We report on a 41-year-old man with hematemesis and severe epigastric pain. Three
      hours after the onset of symptoms, we carefully performed upper gastrointestinal
      endoscopy for suspected upper gastrointestinal perforation. Endoscopy revealed a
      2.5-cm-long longitudinal laceration of the lower esophagus without active gastric
      or duodenal ulcers. The laceration could be partially closed with endoscopic
      clipping. Computed tomography of the chest revealed a small amount of
      extraluminal air in the mediastinum. Neither pleural effusion nor pneumothorax
      was detected. We treated the patient conservatively on the basis of the following
      factors: a stable general condition without sepsis, limitation of the esophageal
      disruption to the mediastinum, and early diagnosis. The treatment course was
      uneventful, and the patient was discharged from the hospital after we had
      confirmed with endoscopy that the esophageal ulcer was completely healed.
      Although Boerhaave syndrome is generally considered to have poor prognosis,
      conservative therapy may be effective in select cases with early detection of the
      perforation.

PMID- 17220587
TI  - Pancreatic arteriovenous malformation involving adjacent duodenum with
      gastrointestinal bleeding: report of a case.
AB  - A 54-year-old man was admitted to our hospital with the symptoms of palpitation,
      dyspnea, and tarry stool. Upper gastroduodenal endoscopy revealed submucosal
      lesions with vascular ectasia in the second part of the duodenum. Dynamic
      computed tomography (CT) detected a hypervascular lesion in the pancreatic head
      and the duodenum. Selective angiography showed proliferation of a vascular
      network and early filling of the portal vein at the early arterial phase. With a
      diagnosis of pancreatic arteriovenous malformation (AVM), we performed pylorus
      preserving pancreaticoduodenectomy. At laparotomy, localized and meandering
      vessels were seen on the surface of the head of the pancreas. Histological
      examination showed dilated tortuous vessels accompanied by severed elastic fibers
      in the vessel media and blood clot formation. The incidence of pancreatic AVM
      remains extremely low, and recurrent gastrointestinal bleeding is a frequent
      complication. To prevent recurrent bleeding and progressive portal hypertension,
      surgery may be the definitive management of symptomatic AVM.

PMID- 17220588
TI  - Influence of placental position on outcome in patients with placental abruption.
AB  - We retrospectively analyzed the clinical significance of placental position in
      patients with placental abruption by comparing cases in which the placenta was
      implanted on the anterior wall of the uterus (n=17) and those in which the
      placenta was on the posterior wall (n=12). There were no significant differences
      in clinical features of patients or pregnancy outcomes between the two groups. In
      this study, all patients with an anterior-wall placenta received a diagnosis of
      placental abruption prenatally, whereas only 8 patients (67%, p=0.01) with
      posterior-wall placenta received a diagnosis of placental abruption prenatally.
      Serious consideration should be given to the diagnosis of placental abruption in
      patients with a posterior-wall placenta.

PMID- 17220592
TI  - Prostaglandin E2 has no effect on two components of tetrodotoxin-resistant Na+
      current in mouse dorsal root ganglion.
AB  - One possible mechanism underlying inflammation-induced sensitization of the
      primary afferent neuron is the upregulation of tetrodotoxin-resistant (TTX-R)
      Na(+) current by inflammatory mediators such as prostaglandins. This notion is
      based on reports that showed an augmentation of TTX-R Na(+) current following an
      application of prostaglandin E(2) (PGE(2)) in dorsal root ganglion (DRG) neurons.
      However, no information was available on the properties of the novel type of TTX
      R Na(+) channel, Na(V)1.9, at times when these reports were published. Hence, the
      contribution of Na(V)1.9 to the PGE(2)-induced upregulation of TTX-R Na(+)
      current remains to be elucidated. To further examine the modulation of TTX-R
      Na(+) current by PGE(2), we recorded two components of TTX-R Na(+) current in
      isolation from small (<25 microm in diameter) DRG neurons using wild-type and
      Na(V)1.8 knock-out mice. Unexpectedly, neither the component mediated by Na(V)1.8
      nor the persistent component mediated by Na(V)1.9 was affected by PGE(2) (1 and
      10 microM). Our results raise a question regarding the well-known modulatory role
      of PGE(2) on TTX-R Na(+) current in inflammatory hyperalgesia.

PMID- 17220593
TI  - Muscarinic receptor subtypes mediating positive and negative inotropy in the
      developing chick ventricle.
AB  - The inotropic response to muscarinic receptor stimulation of isolated chick
      ventricular myocardium was examined at various developmental stages, and the
      receptor subtype involved was pharmacologically characterized. In embryonic chick
      ventricles, carbachol (CCh) produced positive inotropy at micromolar
      concentrations. In hatched chick ventricles, CCh produced negative inotropy at
      nanomolar concentrations. Neither positive nor negative inotropy was observed in
      the 19 - 21-day-old embryos. Both positive and negative inotropy were also
      observed with acetylcholine and oxotremoline-M. The CCh-induced positive inotropy
      in 7 - 9-day-old embryonic ventricles and the negative inotropy in 1 - 3-day-old
      hatched chick ventricles were antagonized by muscarinic receptor antagonists;
      pA(2) values for the positive and negative responses of pirenzepine were 7.5 and
      7.2, those of AF-DX116 (11-[(2-[(diethylamino)methyl]-1-piperidinyl)acetyl]-5,11
      dihydro-6H-pyrido[2,3-b][1,4] benzodiazepine-6-one) were 6.8 and 6.9, those of 4
      diphenylacetoxy-N-methylpiperidine (4-DAMP) were 9.0 and 8.5, and those of
      himbacine were 7.0 and 8.0, respectively. CCh had no effect on action potential
      configuration. In conclusion, the positive inotropy is most likely mediated by
      muscarinic M(1) receptors and the negative inotropy is mostly likely mediated by
      muscarinic M(4) receptors.

PMID- 17220594
TI  - Role of mouse organic anion transporter 3 (mOat3) as a basolateral prostaglandin
      E2 transport pathway.
AB  - Renal organic anion transporters play an important role in the handling of a
      number of endogenous and exogenous anionic substances in the kidney. In this
      study, we investigated prostaglandin E(2) (PGE(2)) transport properties and
      intrarenal localization of mouse organic anion transporter 3 (mOat3). When
      expressed in Xenopus oocytes, mOat3 mediated the time- and concentration
      dependent transport of PGE(2) (K(m): 1.48 microM). PGE(2) transport mediated by
      mOat3 was trans-stimulated by intracellular glutarate injected into the oocytes.
      PGE(2) efflux via mOat3 was also trans-stimulated by extracellular glutarate.
      Thus, mOat3 was shown to mediate the bidirectional transport of PGE(2), partly
      coupled to the dicarboxylate exchange mechanism. Immunohistochemical study
      revealed that mOat3 protein was localized at the basolateral membrane of renal
      proximal and distal tubules. Furthermore, diffuse expression of mOat3, including
      expression in the basolateral membrane in macula densa (MD) cells, was observed.
      These results indicate that mOat3 plays an important role as a basolateral
      transport pathway of PGE(2) in the distal nephron including MD cells that may
      constitute one of the indispensable steps for renin release and regulation of the
      tubuloglomerular feedback mechanism.

PMID- 17220595
TI  - Blockade of leukotriene B4 signaling pathway induces apoptosis and suppresses
      cell proliferation in colon cancer.
AB  - We investigated whether leukotriene B(4) (LTB(4)) and its signaling pathway play
      an important role in the progression of human colon cancer via a direct
      stimulation of cancer cell proliferation. Remarkable expression of LTB(4)
      receptor 1 (BLT1) in human colon cancer tissues was detected by
      immunohistochemistry, and Western blot analysis revealed the BLT1 expression in
      cultured human colon cancer cell lines, Caco2 and HT29. The 5-lipoxygenase
      inhibitor AA-861 and LTB(4)-receptor antagonist U75302 showed negative effects on
      survival and proliferation of both Caco2 and HT-29 cells. The inhibition of cell
      proliferation is due to the apoptosis because nuclear condensation and increased
      annexin V expression were observed in the cells treated with AA-861 and U75302.
      Knockdown of BLT1 by small interfering RNA caused the suppression of BLT1
      protein, resulting in the inhibition of cancer cell proliferation. Blockade of
      BLT1 by the receptor antagonist significantly suppresses the LTB(4)-stimulated
      extracellular signal-regulated kinase (ERK) activation in colon cancer cells.
      These results indicate that the blockade of the LTB(4)-signaling pathway induces
      apoptosis via the inhibition of ERK activation in colon cancer cells. The LTB(4)
      signaling pathway might be a new therapeutic target for colon cancer.

PMID- 17220596
TI  - Manipulation of fish germ cell: visualization, cryopreservation and
      transplantation.
AB  - Germ-cell transplantation has many applications in biology and animal husbandry,
      including investigating the complex processes of germ-cell development and
      differentiation, producing transgenic animals by genetically modifying germline
      cells, and creating broodstock systems in which a target species can be produced
      from a surrogate parent. The germ-cell transplantation technique was initially
      established in chickens using primordial germ cells (PGCs), and was subsequently
      extended to mice using spermatogonial stem cells. Recently, we developed the
      first germ-cell transplantation system in lower vertebrates using fish PGCs and
      spermatogonia. During mammalian germ-cell transplantation, donor spermatogonial
      stem cells are introduced into the seminiferous tubules of the recipient testes.
      By contrast, in the fish germ-cell transplantation system, donor cells are
      microinjected into the peritoneal cavities of newly hatched embryos; this allows
      the donor germ cells to migrate towards, and subsequently colonize, the recipient
      genital ridges. The recipient embryos have immature immune systems, so the donor
      germ cells can survive and even differentiate into mature gametes in their
      allogeneic gonads, ultimately leading to the production of normal offspring. In
      addition, implanted spermatogonia can successfully differentiate into sperm and
      eggs, respectively, in male and female recipients. The results of transplantation
      studies in fish are improving our understanding of the development of germ-cell
      systems during vertebrate evolution.

PMID- 17220597
TI  - Smiling face in the heart.

PMID- 17220598
TI  - Anomalous origin of the right coronary artery.

PMID- 17220599
TI  - Metastatic serous adenocarcinoma arising in the adnexa uteri and forming pleural
      cysts on the diaphragmatic pleura.

PMID- 17220600
TI  - Cutaneous involvement in Hodgkin's disease.

PMID- 17220601
TI  - Segmental muscular atrophy in a patient with post polio syndrome.

PMID- 17220602
TI  - 1. COPD pathogenesis from the viewpoint of risk factors.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by irreversible
      airflow limitation in the lungs. Smoking is one of the amongst major risk factors
      for the development of COPD. Environmental pollution, age, and airway
      hyperreactivity are also the risk factors. The protease-antiprotease imbalance
      and the oxidant-antioxidant imbalance cause airway inflammation and destruction.
      The genes related to these balances may contribute to development of COPD
      pathology. Candidate gene-association studies and linkage analyses have been
      reported for COPD patients. The alpha-1 antitrypsin, glutathione S-transferase,
      microsomal epoxide hydrolase, and matrix metalloproteinase, are candidate genes.
      In acquired factors for COPD pathology, the adenoviral latent infection may
      enhance airway inflammation, leading to airflow obstruction. The current progress
      and future visions of genetic predisposition of COPD are discussed.

PMID- 17220603
TI  - 2. Advances in pharmacotherapy for COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is the most common chronic lung
      disease in the world. In 1999, COPD ranked sixth among the most common causes of
      death and twelfth as a worldwide burden of disease. It has been estimated that by
      the year 2020 COPD will be the third leading cause of death and fifth as a
      worldwide burden of disease. Thus, COPD is a major medical problem and there is
      evidence that it is increasing throughout the world. Despite recognition of COPD
      as an important international health problem, COPD has been neglected among
      common diseases, with little investment in research on its underlying cellular
      and molecular mechanisms. Recently, global and Japanese guidelines for COPD have
      been published. These guidelines seem to be useful to improve the underdiagnosis
      and undertreatment of COPD. In this review, I describe briefly the current
      recommendation for pharmacological therapy of stable COPD according to the global
      and Japanese guidelines for COPD.

PMID- 17220604
TI  - 3. COPD: non-pharmacologic treatment.

PMID- 17220606
TI  - 2. All-trans retinoic acid in the treatment of acute promyelocytic leukemia.

PMID- 17220605
TI  - 1. Molecular target drug discovery.
AB  - Cancer is caused by genetic abnormalities: activation of oncogenes and functional
      inactivation of tumor-suppressor genes. Direct correction of these abnormalities
      should be the essential treatment for cancer; however, we have not developed any
      techniques to effectively fix the genome to date. Molecular biological analyses
      have demonstrated the cancer function of abnormal gene products, activated signal
      transduction pathways, and cancer-specific cell surface antigens. Molecular
      target drugs have been designed to suppress these molecules, important for
      maintaining cancer status, at stages of mRNA and protein. Some targets
      contributing to cancer progression are even within host cells such as angiogenic
      factor receptors. Differing from conventional chemotherapeutic agents screened
      and developed with cytotoxicity to tumor cells, molecular target drugs show
      higher specificity for cancer and sometimes simply stabilize the tumor. The
      effect of such drugs depends on the expression and functional importance of the
      target in cancer, and prediction of the effect using molecular techniques such as
      DNA microarray may be necessary for appropriate use.

PMID- 17220607
TI  - 3. Imatinib therapy in chronic myelogenous leukemia.

PMID- 17220608
TI  - 4. Antibody therapy for malignant lymphoma.
AB  - Rituximab, a genetically engineered, chimeric anti-CD20 monoclonal antibody,
      induces the apoptosis of B-lymphoma cells, in addition to the lyses by complement
      dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity
      (ADCC), as shown in Fig. 1. A Japanese phase I study of rituximab in relapsed or
      refractory patients with B-cell non-Hodgkin's lymphoma (B-NHL) showed an overall
      response rate (ORR) of 64% (7/11) with minimal toxicities. Elimination half-life
      (T(1/2)) of serum rituximab was 445+/-361 hours, and the serum rituximab was
      detectable at three months. In the subsequent phase II study, 90 relapsed or
      refractory patients with indolent B-NHL or mantle cell lymphoma (MCL) were
      treated with rituximab at 375 mg/m2x4 weekly infusions. ORRs in indolent B-NHL
      and MCL were 61% (37/61) and 46% (6/13), respectively. In this presentation, the
      results of clinical trials of antibody therapy of malignant lymphoma are
      summarized, focusing on the two recent Japanese multicenter trials of rituximab
      and a Japanese feasibility study of anti-CD20 radioimmunotherapy with yttrium-90
      lableled ibritumomab tiuxetan.

PMID- 17220609
TI  - 1. Fatty liver and non-alcoholic steatohepatitis.
AB  - Although steatohepatitis can be induced by an excessive intake of alcohol, it can
      also arise through various other causes, in which case it is known as non
      alcoholic fatty liver disease (NAFLD). NAFLD is classified into two
      categories:simple fatty liver with a favorable clinical outcome, and non
      alcoholic steatohepatitis (NASH), which is intractable and progressive. Recently
      in Japan, there has been an increase in the number of individuals at risk of
      lifestyle-related diseases, due to increased insulin resistance and visceral fat
      obesity. The metabolic syndrome (MS) is associated with several risk factors for
      atherosclerosis, including diabetes mellitus (DM), hypertension, and
      hyperlipidemia. Visceral fat obesity is the prime cause of NASH in the liver, and
      is therefore considered to be one of the phenotypic features of MS. Furthermore,
      most chronic liver diseases are associated with hepatitis C virus (HCV)
      infection. Fatty degeneration of hepatocytes is often observed in the liver of
      HCV-infected individuals, and results from viral suppression of mitochondrial
      beta-oxidation of fatty acid. The natural outcome of HCV infection is worse in
      patients with lifestyle-related high insulin resistance and visceral fat obesity.
      In this review, we describe the recent advances in research on progressive liver
      diseases that are the result of fat accumulation in the liver, with special
      reference to MS.

PMID- 17220610
TI  - 2. Lifestyle-related diseases and Helicobacter pylori infection.

PMID- 17220611
TI  - 3. Metabolic syndrome and inflammatory bowel disease.

PMID- 17220612
TI  - 4. Chronic pancreatitis and pancreatic cancer, lifestyle-related diseases.
AB  - In Japan, the number of patients with both chronic pancreatitis (CP) and
      pancreatic cancer (PC) is increasing. A nationwide survey on CP revealed that the
      total number of patients treated for CP in Japan in 2002 was estimated as 45,200
      (95% confidence interval, 35,600-54,700), and 20,137 patients died of PC in 2002.
      Alcoholic pancreatitis was the most common type of pancreatitis (67.5 %).
      Cigarette smoking was an independent and significant risk factor for CP. The
      risks of pancreatic and nonpancreatic cancers increased in the course of CP.
      While alcohol consumption may increase the risk of PC via CP, smoking was
      important as a risk factor for both CP and PC. The increasing incidence of PC was
      closely related to the increasing intake of animal fat. Lifestyle in patients
      with CP appeared to be the same as that in patients with PC. Environmental
      factors such as lifestyle in combination with genetic factors may increase the
      risk for both CP and PC. Therefore, changing and improving lifestyle habits such
      as drinking, smoking and nutrition may reduce the risks for both CP and PC.

PMID- 17220613
TI  - Oral pyogenic granuloma: a review.
AB  - Pyogenic granuloma is one of the inflammatory hyperplasias seen in the oral
      cavity. This term is a misnomer because the lesion is unrelated to infection and
      in reality arises in response to various stimuli such as low-grade local
      irritation, traumatic injury or hormonal factors. It predominantly occurs in the
      second decade of life in young females, possibly because of the vascular effects
      of female hormones. Clinically, oral pyogenic granuloma is a smooth or lobulated
      exophytic lesion manifesting as small, red erythematous papules on a pedunculated
      or sometimes sessile base, which is usually hemorrhagic. The surface ranges from
      pink to red to purple, depending on the age of the lesion. Although excisional
      surgery is the treatment of choice for it, some other treatment protocols such as
      the use of Nd:YAG laser, flash lamp pulsed dye laser, cryosurgery, intralesional
      injection of ethanol or corticosteroid and sodium tetradecyl sulfate
      sclerotherapy have been proposed. Because of the high frequency of pyogenic
      granuloma in the oral cavity, especially during pregnancy, and necessity for
      proper diagnosis and treatment, a complete review of published information and
      investigations about this lesion, in addition to knowledge about new approaches
      for its treatment is presented.

PMID- 17220614
TI  - Screening of periodontitis with salivary enzyme tests.
AB  - The purpose of this study was to determine the usefulness of salivary biochemical
      markers for the screening of periodontal disease and examine the agreement
      between the results of saliva enzyme tests and those of probing depth. The
      present study included a total of 187 subjects who underwent annual medical check
      ups at the Comprehensive Health Care Center, Honjo, Saitama Prefecture, Japan.
      Periodontal pocket probing was performed with a WHO probe, and various enzymes
      and biochemical parameters in saliva were measured. For lactate dehydrogenase
      (LDH), the proportions of the five isoenzymes were calculated. To decide the cut
      off point for each enzymatic activity, receiver operating characteristic curves
      (ROC curves) were constructed and the points of minimum difference between
      sensitivity and specificity were decided. Among the biochemical markers tested,
      salivary LDH level had the highest sensitivity and specificity (sensitivity 0.66,
      specificity 0.67), while salivary levels of aspartate aminotransferase (AST) and
      blood urea nitrogen (BUN) also had sensitivity and specificity above 0.60. Among
      the LDH isoenzymes, LDH4 and LDH5 dominated in whole saliva samples. Salivary LDH
      may be a feasible and useful parameter for the screening of periodontal disease,
      while salivary AST and BUN also appear to be potentially useful for this purpose.

PMID- 17220615
TI  - Histochemical analysis of pathological alterations in oral lichen planus and oral
      lichenoid lesions.
AB  - Lichen planus is a dermatologic disease of unknown etiology characterized by
      keratotic plaques on the skin. Many patients also harbor white lesions of the
      oral mucosa. The literature contains numerous reports of lichen planus-like
      lesions evolving in conjunction with the administration of a variety of
      pharmacologic agents. It is difficult, if not impossible, to distinguish such
      lesions from one another. The present study evaluated the epithelial and basement
      membrane thickness, mast cells (intact cells and degranulated cells
      subepithelially) and the presence or absence of blood vessels in oral lichen
      planus and oral lichenoid lesions. The evaluation was done using the periodic
      acid-schiff (PAS) and toluidine blue staining techniques on 20 cases each of oral
      lichen planus and oral lichenoid lesions and 5 control specimens of normal buccal
      mucosa. The results showed an increased number of degranulated mast cells in
      areas of basement membrane degeneration, increased vascularity and increased PAS
      positive basement membrane thickness in oral lichen planus as compared with oral
      lichenoid lesions. Reduced epithelial thickness was found in oral lichen planus.
      The present study emphasizes the importance of these parameters in
      differentiating oral lichen planus from oral lichenoid lesions using special
      staining techniques.

PMID- 17220616
TI  - Diabetes and its effects on dental pulp.
AB  - Uncontrolled or poorly controlled diabetes mellitus may be a risk factor for the
      development of oral complications. The objective of this investigation was to
      determine the effect of diabetes mellitus progression on inflammatory and
      structural components of dental pulp. Male Wistar rats were given a single
      injection of Streptozotocin (STZ), and induction of diabetes was confirmed 24 h
      later. Dental pulp tissue samples were taken from central incisors and molars of
      diabetic rats 30 and 90 days after the STZ treatment. Plasma glucose levels in
      diabetic rats 30 and 90 days after STZ treatment were significantly increased
      when compared to control rats (P < 0.001). Nitrite and kallikrein levels in
      dental pulp tissue were higher in diabetic rats 30 days after STZ treatment than
      in controls, while only nitrite were decreased 90 after of STZ treatment.
      Myeloperoxidase activity showed changes 30 and 90 days after STZ injection when
      compared to controls. The activity of alkaline phosphatase showed significant
      changes 30 and 90 days after STZ treatment. On the other hand the concentration
      of collagen was decreased in diabetic rats 30 and 90 days after STZ injection.
      These results suggest that diabetes is a critical factor that has profound
      effects upon oral tissues, resulting in expression of inflammatory mediators and
      modifications of structural components of dental pulp.

PMID- 17220617
TI  - Biocompatibility of natural latex implanted into dental alveolus of rats.
AB  - The present study investigated the biocompatibility of a biopolymer based on
      vegetable latex extracted from the Hevea brasiliensis rubber tree, implanted into
      the bony alveolar cavity after dental extraction in rats. A granule of latex
      (area = 0.25 +/- 0.04 mm(2)) was implanted inside the alveolus immediately after
      extraction of the upper right incisor, and the animals were sacrificed 7, 21 and
      42 days after the procedure. The hemi-maxillas were decalcified and processed for
      embedding in paraffin to obtain semi-serial longitudinal sections 5 mum thick,
      and then stained with hematoxylin-eosin. The latex granule was observed in the
      cervical third of the alveolus without any foreign body reaction, or persistence
      of the initial acute inflammatory reaction. Bone repair in the areas adjacent to
      the material was quantified, and a decrease was noted in the thickness of the
      fibrous capsule surrounding the implants from 92.8 +/- 9.3 microm on day 7 to 9.4
      +/- 1.8 microm on day 42 (ANOVA, P = 0.01). The quantitative data confirmed
      acceleration of bone formation (statistically significant at 5%) in parallel with
      a decrease of connective tissue in the areas around the implants. These results
      show that the tested material is biologically compatible, and progressively
      integrated into the alveolar bone, simultaneously accelerating bone formation and
      playing an important role in the healing process.

PMID- 17220618
TI  - Histological analysis of effects of 24% EDTA gel for nonsurgical treatment of
      periodontal tissues.
AB  - The aim of this study was to investigate, by means of histological and
      histomorphometric analysis, the effects of 24% ethylenediaminetetraacetic acid
      (EDTA) gel in periodontal tissue when used in combination with conventional
      periodontal treatment. Periodontitis was induced in the 2nd upper left permanent
      molars of 45 male Wistar rats by means of ligature. After 5 weeks, this was
      removed and debridement was performed. The animals were then randomly divided
      into 3 groups; group 1: mechanical treatment, group 2: mechanical treatment and
      EDTA gel application for 2 min, and group 3: mechanical treatment and placebo gel
      application for 2 min. After the treatment, rinsing was done with 0.9% saline
      solution for 1 min in all cases, followed by root notching in the deepest part of
      the pocket. After 4, 10, and 28 days the animals were sacrificed. The averages
      obtained were evaluated by means of test two-way analysis of variance (ANOVA) and
      Tukey statistical tests (P < 0.05). The results showed that with respect to the
      type of treatment employed, there were no statistically significant differences
      in the vitality of the periodontal tissue. It was concluded that 24% EDTA gel did
      not interfere with periodontal tissue repair when used in combination with
      conventional periodontal treatment.

PMID- 17220619
TI  - Effect of metal priming agents on bonding characteristics of an acrylic resin
      joined to SUS XM27 steel.
AB  - The purpose of the current study was to evaluate the effect of functional
      monomers contained in the primers on adhesive bonding of a steel alloy. SUS XM27
      steel was primed with one of the following materials; Alloy Primer, Estenia
      Opaque Primer, and V-Primer. The functional monomers in the primers were a
      phosphate (10-methacryloyloxydecyl dihydrogen phosphate; MDP) and a thione (6-(4
      vinylbenzyl-n-propyl) amino-1,3,5-triazine-2,4-dithione, -dithiol tautomer; VTD)
      for Alloy Primer, MDP alone for Estenia, and VTD alone for V-Primer. The steel
      disks were bonded with an acrylic resin (Unifast Trad), and bond strength was
      determined. Of the three primers, both the Alloy Primer (33.3 MPa) and Estenia
      Opaque Primer (33.9 MPa) materials exhibited far better post-thermocycling bond
      strength than V-Primer (0 MPa). It can be concluded that the phosphate MDP is
      effective, whereas the thione VTD is ineffective for bonding SUS XM27 steel.

PMID- 17220620
TI  - Physico-chemical characterization and biocompatibility evaluation of
      hydroxyapatites.
AB  - The aim of this study was to evaluate the physico-chemical and biocompatibility
      characteristics of two different hydroxyapatites. Physical and chemical
      properties were analyzed using granulometric analysis, scanning electron
      microscopy (SEM), X-ray energy-dispersion (EDX), X-ray fuorescence (XRF) and X
      ray diffraction (XRD). Biomaterials were implanted into the subcutaneous tissue
      on the dorsum of 36 Wistar rats, divided into the following groups: Group 1 - Gen
      Ox (natural); Group 2 - HA-U (synthetic) and Group 3 - Control (Sham). After 15
      and 30 days, 6 animals/period were sacrificed and the subcutaneous tissue was
      taken for histological and histometric analysis, giving consideration to
      inflammatory reaction and granule area. The granulometric test results showed a
      mean granule diameter of 161.6 microm (min = 19.0 microm; max = 498.0 microm) and
      48.7 microm (min = 7.0 microm; max = 256.0 microm) for groups 1 and 2
      respectively. Analysis with SEM demonstrated irregular and sharp-edge particles
      in group 1 (3332.8 +/- 274.3 microm(2)) and irregular and rounded particles in
      group 2 (1320.8 +/- 83.0 microm(2)) (P < 0.0001; Student's t test). EDX and XRF
      revealed calcium, carbon, oxygen, sodium and phosphorus in both groups. XRD
      indicated that both biomaterials were pure and crystalline. There was a
      statistically significant difference in granule area between the two groups after
      15 days (P = 0.022; Student's t-test). After 15 days, an increased inflammatory
      response was seen in group 2 (P < 0.0001; ANOVA and Tukey's post hoc test)
      whereas it was more pronounced in group 1 after 30 days (P < 0.0001; ANOVA and
      Tukey's post hoc test). It was concluded that these biomaterials have similar
      physical, chemical and biocompatibility characteristics.

PMID- 17220621
TI  - Inhibition of Porphyromonas gingivalis hemagglutinating activity by IgY against a
      truncated HagA.
AB  - Porphyromonas gingivalis has been implicated as an important pathogen in the
      development of periodontitis. Hemagglutinins have been identified as important
      adhesion molecules, allowing Porphyromonas gingivalis to adhere to gingival
      tissue cells, and to attach and lyse erythrocytes in order to uptake Fe ions as
      essential nutrition. One hemagglutinin, hemagglutinin A (HagA), has been
      molecularly cloned via functional screening for hemagglutinating activity. We
      previously cloned the gene encoding the 200-kDa cell-surface antigenic protein
      that was reacted by sera from periodontitis patients and was identified as a
      truncated protein of HagA by nucleotide sequence analysis. We further subcloned
      the gene encoding an 122-kDa protein (122k-HagA) which is a fusion protein
      composed of an 80-kDa truncated HagA containing the functional motif PVQNLT and a
      42-kDa maltose binding protein. Passive immunization against infectious pathogens
      by specific antibodies produced from hen egg yolk antibody (IgY) has been
      extensively developed. In the present study, to develop passive immunotherapy
      against periodontal disease, we purified the recombinant 122k-HagA and used this
      to immunize hens and produce IgY. The purified IgY reacted with the recombinant
      122k-HagA and the synthetic peptide containing PVQNLT, and inhibited
      hemagglutinating activity of Porphyromonas gingivalis. Thus, the novel IgY may be
      useful in the development of a passive immunization against periodontal diseases
      caused by P. gingivalis infection.

PMID- 17220622
TI  - Employing dmft score as a risk predictor for caries development in the permanent
      teeth in Japanese primary school girls.
AB  - The aim of this study was to examine the significance of evaluating dmft for
      predicting the incidence of permanent teeth caries in Japanese girls. The
      subjects were two birth cohorts in a Primary girls' school: cohort I composed of
      45 girls born in 1981 and 1982 and cohort II composed of 53 girls born in 1989
      and 1990. In both cohorts, there was a significant correlation between the dmft
      score in the first grade and the DMFT score in the sixth grade. The validity of
      employing dmft score was examined by receiver operating characteristic (ROC)
      curve and risk ratios. The shape of the curve and areas under the curve were
      similar in the two cohorts. In cohort II, sensitivity and specificity for the
      optimal cut-off level (dmft >or= 5) were 0.519 and 0.923, respectively. The
      positive and negative predictive values for that level were 0.875 and 0.649,
      respectively. In cohort I, sensitivity and specificity were 0.741 and 0.722 for
      that level and positive and negative predictive values were 0.800 and 0.650,
      respectively. In both cohorts, the risk ratio for permanent teeth caries was
      significant for many cut-off levels of dmft. The results indicated that the dmft
      score is a useful predictor of the permanent teeth caries in Japanese primary
      school girls.

PMID- 17220623
TI  - Multicentric peripheral ossifying fibroma.
AB  - Peripheral ossifying fibroma (POF) is a common solitary gingival growth thought
      to arise from the periodontal ligament. Though the etiology of POF remains
      unknown, some investigators consider it an inflammatory or reactive process,
      while others suggest it is a neoplastic process. In this report, we present and
      discuss a unique case of multicentric POF, affecting the maxillary and mandibular
      gingiva of a 49-year-old Caucasian female with meticulous oral hygiene and
      routine dental care. Though biopsy samples from multiple sites revealed similar
      histopathologic features, consistent with POF, the fact that there was a
      multicentric presentation is a unique phenomenon for this lesion. Multicentric
      lesions presenting in the oral and maxillofacial region are not typical, but have
      been observed in conditions associated with known genetic mutations, such as
      nevoid basal cell carcinoma syndrome (multiple odontogenic keratocysts), multiple
      endocrine neoplasia type II (multiple neuromas), neurofibromatosis (multiple
      neurofibromas) and Gardner syndrome (multiple neoplasms). This case is the first
      one to demonstrate that there may be a multicentric variant of POF that has not
      been previously recognized, and given the clinical presentation and multifocal
      nature of disease, the lesions in this patient are likely the result of genetic
      mutation(s) that predisposes to gingival soft tissue overgrowths containing
      mineralized product.

PMID- 17220624
TI  - Correlation of cariogenic bacteria and dental caries in adults.
AB  - Many studies suggest that mutans streptococci (MS), Lactobacillus (LB), and
      salivary buffering capacity are important risk factors for dental caries.
      However, target populations for most studies were children. In adult patients,
      the same risk factors affect the number of fillings or prostheses or secondary
      caries. It is therefore important to investigate these risk factors as predictors
      of caries in adults. In the present study, we evaluated the oral conditions of
      adult subjects at private dental offices using bite-wing radiographs. Detection
      of salivary LB level using Dentocult LB had a statistically significant
      correlation with the number of flat surface caries and approximal caries (P <
      0.001). Detection of salivary MS level using Dentocult MS and salivary buffering
      capacity did not predict dental caries. Thus, detection of salivary LB level
      using Dentocult LB may be a useful tool for detecting approximal and secondary
      caries.

PMID- 17220625
TI  - Pigmented mucoepidermoid carcinoma, a case report and review of the literature on
      melanin-pigmented salivary gland tumors.
AB  - This paper reports a well-differentiated mucoepidermoid carcinoma containing
      numerous melanocytes in the parenchyma in a middle-aged Japanese man. In addition
      to the characteristic histopathologic features of well-differentiated
      mucoepidermoid carcinoma, various-formed and -sized, pigmented cells were widely
      distributed in the parenchyma. Many of these were considered to be melanocytes
      containing melanin in their cytoplasm. Perusal of the English-language literature
      revealed only four cases of salivary gland tumors with parenchymal pigmentation:
      three mucoepidermoid carcinomas and one pleomorphic adenoma. The possible
      histogenesis of melanocytes in the salivary gland lesions is discussed, although
      no firm conclusion could be drawn.

PMID- 17220626
TI  - Papillon-Lefevre syndrome: a highly-suspected case.
AB  - Papillon-Lefevre syndrome (PLS) is characterized by severe periodontal disease
      extending to destruction of the alveolar bone surrounding deciduous teeth and
      palmoplantar hyperkeratosis of the skin. Increased susceptibility to infection
      has been reported among individuals with the cathepsin C (CTSC) gene mutation.
      This article reports a 7-year-old Japanese girl who presented with deciduous
      tooth mobility and was diagnosed as having PLS. Radiographic examination revealed
      loosening of deciduous incisors and the right second molar of the maxilla, and
      destruction of the alveolar bone around the residual deciduous dentition.
      However, there was no destruction of the alveolar bone around the permanent
      molars. The patient did not show the typical signs of CTSC polymorphism, which
      almost always negatively impacts certain activating enzymes. With respect to
      immune function, analysis of the patient's leukocytes indicated that H(2)O(2),
      chemotactic and phagocytotic functions were within the normal range. However, the
      special precautions normally applied to prevent infections in PLS patients
      undergoing dental treatment were taken.

PMID- 17220627
TI  - Porcelain laminate veneer restorations bonded with a three-liquid silane bonding
      agent and a dual-activated luting composite.
AB  - This clinical report describes the fabrication and bonding of porcelain laminate
      veneer restorations in a patient with anterior open spaces. Laminate veneer
      restorations made of feldspathic porcelain were etched with 5% hydrofluoric acid,
      rinsed under tap water, ultrasonically cleaned with methanol, and primed with a
      chemically activated three-liquid silane bonding agent (Clearfil Porcelain Bond).
      The enamel surfaces were etched with 40% phosphoric acid, rinsed with water, and
      primed with a two-liquid bonding agent (Clearfil New Bond) that contained a
      hydrophobic phosphate (10-methacryloyloxydecyl dihydrogen phosphate; MDP). The
      restorations were bonded with a dual-activated luting composite (Clapearl DC).
      The veneers have been functioning satisfactorily for an observation period of one
      year. Combined use of the Clearfil bonding agents and Clapearl DC luting
      composite is an alternative to conventional materials for seating porcelain
      laminate veneer restorations, although the system is inapplicable to dentin
      bonding.

PMID- 17220628
TI  - Clinical and neuropsychological features associated with structural imaging
      patterns in patients with mild cognitive impairment.
AB  - AIM: To describe the clinical and neuropsychological features of mild cognitive
      impairment (MCI) patients with medial temporal atrophy (MTA), white matter
      hyperintensities (WMH), both, and neither and to assess whether the rate of
      progression differs among groups. METHODS: Ninety-five MCI patients were divided
      into 4 groups based on the presence of MTA and WMH: 29 were MTA- WMH-, 11 MTA-
      WMH+, 23 MTA+ WMH-, and 32 MTA+ WMH+. MCI patients were compared with 30 normal
      subjects. MTA and WMH were assessed with MR-based visual rating scales. Subjects
      underwent an extensive clinical and neuropsychological investigation. Fifty-six
      underwent follow-up evaluation. RESULTS: MTA- WMH- had relatively good
      neuropsychological performance, little vascular and physical comorbidity. MTA-
      WMH+ performed poorly only on executive neuropsychological tests. MTA+ WMH-
      patients had poor neuropsychological performances (mainly on memory tests), high
      physical and vascular comorbidity. MTA+ WMH+ were impaired in neuropsychological
      performances, had a high number of physical diseases and severe vascular
      comorbidity. On follow-up, 25% of MTA+ WMH- and 32% of MTA+ WMH+ and none in MTA-
      WMH- and in MTA- WMH+ converted to dementia (p = 0.05, log rank test).
      CONCLUSION: Structural neuroimaging can identify subgroups of MCI patients with
      specific clinical and neuropsychological features.

PMID- 17220629
TI  - Utility of behavioral versus cognitive measures in differentiating between
      subtypes of frontotemporal lobar degeneration and Alzheimer's disease.
AB  - We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI
      mod), along with a few cognitive tests, would be clinically useful in
      distinguishing between clinically defined Alzheimer's disease (AD) and subtypes
      of frontotemporal lobar degeneration (FTLD): frontotemporal dementia
      (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We
      studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the
      basis of a comprehensive neuropsychological battery, imaging, neurological
      examination, and history. We found significant between-group differences on the
      FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning
      and delayed recall), and the Trail Making Test Part B (one measure of 'executive
      functioning'). AD was characterized by relatively severe impairment in verbal
      learning, delayed recall, and executive functioning, with relatively normal
      scores on the FBI-mod. Frontotemporal dementia was characterized by relatively
      severe impairment on the FBI-mod and executive functioning in the absence of
      severe impairment in verbal learning and recall. Progressive nonfluent aphasia
      was characterized by severe impairment in executive functioning with relatively
      normal scores on verbal learning and recall and FBI-mod. Finally, semantic
      dementia was characterized by relatively severe deficits in delayed recall, but
      relatively normal performance on new learning, executive functioning, and on FBI
      mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction
      with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B
      categorized the majority of patients as subtypes of FTLD or AD in the same way as
      a full neuropsychological battery, neurological examination, complete history,
      and imaging. These tests may be useful for efficient clinical diagnosis, although
      progressive nonfluent aphasia and semantic dementia are likely to be best
      distinguished by language tests not included in standard neuropsychological test
      batteries.

PMID- 17220630
TI  - Stomach and gallbladder under fat control?

PMID- 17220631
TI  - Role of free fatty acids in regulating gastric emptying and gallbladder
      contraction.
AB  - The limited effectiveness of orlistat, an inhibitor of gastrointestinal lipases,
      in inhibiting fat digestion is not completely understood. Therefore we studied
      the effect of orally and duodenally administered orlistat on gastric emptying,
      cholecystokinin (CCK) secretion, and gallbladder contraction. In healthy males,
      gastric emptying of solids and fat were quantified scintigraphically, gallbladder
      contraction by ultrasound and CCK release by radioimmunoassay. Three studies were
      performed: (1) oral and (2) duodenal orlistat with a fat-containing meal, and (3)
      duodenal orlistat with a fat-free meal. Gastric emptying rates of solids and fat
      (T50% accelerated by 16 and by 22%, p < 0.05, respectively) were significantly
      faster after duodenal perfusion of orlistat; gallbladder contraction and CCK
      release were reduced under these conditions (p < 0.005, respectively). With oral
      orlistat no significant effect was documented on these parameters. We conclude
      that fat hydrolysis is essential in the regulation of fat-induced gastric
      emptying and gallbladder contraction.

PMID- 17220632
TI  - Steroid-dependent ACTH-produced thymic carcinoid: regulation of POMC gene
      expression by cortisol via methylation of its promoter region.
AB  - AIMS: Metyrapone causes a decrease in the serum cortisol level without affecting
      ACTH production in ectopic tumors. We report a case who presented with Cushing's
      syndrome due to an ectopic ACTH-producing thymic carcinoid. In the present case,
      it was demonstrated that metyrapone administration resulted in a significant
      decrease in the plasma ACTH and serum cortisol levels. We hypothesized that the
      steroid hormone may promote proopiomelanocortin (POMC) gene expression in the
      carcinoid cells. METHODS: An 11-year-old boy presented with Cushing's syndrome.
      Prior to the detection of a thymic tumor, metyrapone was administered to
      ameliorate the symptoms of Cushing's syndrome. Interestingly, plasma ACTH as well
      as serum cortisol levels immediately decreased after metyrapone administration.
      The levels of cortisol and ACTH were observed to be normal after complete
      surgical resection of the tumor. Biological characterization of the tumor cells
      was by in vitro analysis. RESULTS: Thein vitro culture of the tumor cells showed
      an increased expression of POMC in the presence of cortisol. A CpG methylation
      assay showed that the demethylation of the POMC promoter was induced by a steroid
      hormone. CONCLUSION: These findings suggest that the ectopic ACTH-producing tumor
      may partly be regulated by the elevated levels of cortisol.

PMID- 17220633
TI  - Longitudinal study of the simultaneous secretion of melatonin and leptin during
      normal puberty.
AB  - BACKGROUND/AIMS: Pubertal changes are a consequence of the activation of the
      hypothalamic-pituitary-gonadal axis due to an increase in the frequency and
      magnitude of pulses of gonadotropin-releasing hormone (GnRH), which may depend on
      the intrinsic properties of the neurons of the hypothalamic arcuatus nucleus, or
      on the influence of neurotransmitters and/or neuromodulators. We evaluated the
      serum concentrations of melatonin and leptin in healthy prepubertal and
      adolescent subjects of both sexes, to define their participation at the initial
      stages and during the progression of pubertal development. METHODS: 80 pediatric
      subjects (47 females and 33 males), aged 6-18 years, were divided into 2 groups,
      prepubertal (n = 25) and adolescent (n = 55), according to the absence or
      presence, respectively, of physical signs of pubertal development. The subjects
      were assessed on two occasions: at the time of their inclusion in the study, and
      12-18 months later when the subject had advanced one pubertal stage according to
      the Tanner classification. Blood was obtained in fasting for clinical purposes
      and for the hormonal study. Melatonin and leptin were measured by
      radioimmunoanalysis. RESULTS: As described previously, melatonin decreases at the
      onset of puberty and during pubertal development. Both the absolute melatonin
      value and the decrease between evaluations tended to be greater in females; the
      variations were correlated with neither an increase in body weight nor with the
      degree of pubertal development. The concentration of leptin increased in both
      sexes with the progression of puberty, this value being 40% greater in women, and
      correlated with the indicators of an increase in body volume and fat
      accumulation. Although its concentration remained stable between evaluations for
      both sexes, among the males the association between leptin and pubertal
      development took place at the start of the process, while for the females we
      observed a significant overall association between pubertal stage and leptin
      concentration, this association being stronger at more advanced Tanner stages.
      Neither at the onset of puberty nor during its course did we observe any
      significant relation between melatonin concentration and any of the Tanner
      stages, whether for males or for females. Neither was there any correlation
      between the absolute values or rates of modification of melatonin and leptin.
      CONCLUSION: According to the evolutionary dynamics of their respective
      concentrations, both initially and during pubertal progress, melatonin and leptin
      do not interact in the initiation or progression of human pubertal development,
      and do not seem to play a key role in this process.

PMID- 17220634
TI  - Preserved bone health in adolescent elite rhythmic gymnasts despite
      hypoleptinemia.
AB  - BACKGROUND/AIMS: Leptin is linked to hormonal disturbances occurring in anorexia
      and positively linked with bone mineral density. The aim of this study was to
      determine whether hypoleptinemia occurring in rhythmic gymnasts may affect bone
      health. METHOD: Leptin, insulin, cortisol, IGF1 levels and bone markers were
      determined in 36 rhythmic gymnasts (EG) and 20 controls (C). Body composition,
      BMD at the whole body (WBBMD), lumbar spine (LSBMD) and bone ultrasound
      properties (SOS, BUA) were measured. RESULTS: The rhythmic gymnasts had lower fat
      mass and leptin level than the controls. There was no difference for IGF1,
      cortisol and insulin levels. Bone turnover rate was higher in elite gymnasts. The
      uncoupling index showed that remodeling favored the bone formation. LSBMD, WBBMD,
      SOS and BUA were higher in elite gymnasts after adjustment for fat mass. Leptin
      correlated positively with fat mass and negatively with physical activity.
      CONCLUSION: High impact training is able to counterbalance bone effects usually
      encountered in hormonally disturbed subjects. Our results suggest that
      hypoleptinaemia might be related to direct osteogenic effects and indirect
      hormonal mechanisms including preservation of IGF and cortisol levels.

PMID- 17220635
TI  - Puberty, exercise and bone health.

PMID- 17220636
TI  - Association between haptoglobin gene variants and diabetic nephropathy:
      haptoglobin polymorphism in nephropathy susceptibility.
AB  - BACKGROUND/AIMS: The Hp(1)/Hp(2) DNA polymorphism has previously been implicated
      in susceptibility to diabetic nephropathy in some but not all studies. In an
      attempt to clarify these conflicting findings, we conducted a case-control
      association study in a Caucasian population. METHODS: We recruited 224 and 285
      type 1 diabetic patients with (cases) and without (controls) nephropathy,
      respectively, from 2 centres based in Northern Ireland and the Republic of
      Ireland. Hp(1)/Hp(2) genotyping was performed using a combination of long-range
      and multiplex PCR. Allele and genotype frequencies in cases and controls were
      compared using the chi(2) test. RESULTS: There was a statistically significant
      increase in the frequency of the Hp(2) allele in cases compared to controls (65.6
      vs. 58.6%, OR = 1.35, 95% CI: 1.04-1.76, p = 0.03). The distributions of
      genotypes were in Hardy-Weinberg equilibrium for both cases and controls, and the
      overall frequency of the Hp(1) allele was 38.3%, which is similar to that found
      in other Western European populations. CONCLUSIONS: The results suggest that the
      Hp(2) allele may confer susceptibility to nephropathy in patients with type 1
      diabetes.

PMID- 17220637
TI  - Opioids induce renal abnormalities in tumor-bearing mice.
AB  - BACKGROUND/AIMS: The etiology of renal dysfunction in cancer patients is likely
      to be multifactorial. A large proportion of these patients receive opioid
      analgesics, but whether opioids contribute to renal dysfunction remains
      uncertain. In a murine cancer model, we examined the effects of chronic opioid
      administration on renal function and pathology, and the molecular mechanisms
      involved. METHODS: C3H/HeJ mice implanted with 2472 tumor cells were treated with
      either morphine or hydromorphone in clinically relevant doses, or PBS (controls).
      Renal function was assessed by blood and urine chemistry as well as by measuring
      mean arterial pressure (MAP) and kidney perfusion. Pathological changes in the
      kidneys were examined by routine histology. Molecular changes were examined by
      assessing eNOS, iNOS, HO-1 and COX-2 expression in whole-kidney lysates by
      Western immunoblotting, and cellular colocalization of these enzymes was
      determined using immunofluorescence microscopy. RESULTS: Three weeks of opioid
      treatment resulted in increased kidney weight, elevated BUN and proteinuria, and
      decreased MAP. This was accompanied by histological abnormalities including
      glomerular enlargement, hypercellularity, peritubular congestion, vasodilatation
      and tubular casts. The vasoregulatory molecules iNOS, eNOS, HO-1 and COX-2 were
      upregulated in the kidneys. The NOS inhibitor L-NAME prevented the morphine
      induced increase in perfusion and kidney weight. CONCLUSIONS: The chronic use of
      clinically relevant doses of opioidsleads to structural kidney abnormalities,
      upregulates NOS, COX-2 and HO-1, and results in renal dysfunction in a murine
      model of cancer.

PMID- 17220638
TI  - Phosphate salivary secretion in hemodialysis patients: implications for the
      treatment of hyperphosphatemia.
AB  - BACKGROUND/AIMS: Hyperphosphatemia is recognized as contributing to the increased
      risk of cardiac death in end-stage renal disease (ESRD) and hemodialysis (HD)
      patients. Currently available pharmacologic treatment for hyperphosphatemia is
      based on phosphate binders but, despite treatment, only half of the patients fall
      within the range for serum phosphorus of the K/DOQI guidelines. Therefore, there
      is a need to identify other therapeutic approaches in order to reduce serum
      phosphate. Salivary fluid contains phosphate which, if related to the daily
      salivary secretion (1,000-1,880 ml), may raise interest in order to identify
      further additive approaches to phosphorus removal in uremic patients, while data
      about salivary phosphate secretion in ESRD patients are controversial. METHODS:
      This study evaluates salivary phosphate secretion in 68 HD patients compared with
      30 healthy subjects. Saxon's test confirmed normal salivary function in patients
      and controls. Salivary calcium and serum phosphate, calcium and PTH were also
      measured. RESULTS: HD patients had significantly higher salivary phosphorus
      levels compared with healthy controls: 30.35 (26.5-34.6) vs. 12.1 (10.58-14.73)
      mg/dl (p < 0.0001), and this significantly correlated (p < 0.0001) with serum
      phosphorus. Multiple regression analysis confirmed serum phosphorus as the only
      predictor (p < 0.0001) of salivary phosphorus. CONCLUSIONS: Given the functional
      secretive similarity between salivary glands and the kidneys, this increased
      salivary phosphate secretion might be interpreted as being compensatory in the
      presence of renal failure. Absorption of the increased salivary phosphate
      secretion, however, may worsen hyperphosphatemia; therefore, the binding of
      salivary phosphate might be considered as a further therapeutic approach to
      hyperphosphatemia in ESRD.

PMID- 17220639
TI  - Activity of rituximab plus cyclophosphamide, doxorubicin/mitoxantrone,
      vincristine and prednisone in patients with relapsed MALT lymphoma.
AB  - BACKGROUND: Various chemotherapeutic agents as well as the anti-CD20 antibody
      rituximab (R) have been tested in patients with mucosa-associated lymphoid tissue
      (MALT) lymphoma, but no standard chemotherapeutic regimen has emerged so far.
      Judging from the data obtained in various types of lymphoma, the activity of R
      appears to be enhanced by combination with chemotherapy. As no data on this topic
      exist for MALT lymphoma, we have retrospectively analysed our experience with R
      plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone (R
      CHOP/R-CNOP) in patients with relapsed MALT lymphoma. PATIENTS AND METHODS: A
      total of 26 patients were identified, 15 were administered R-CHOP while 11
      patients were given R-CNOP due to age >65 years or pre-existing cardiac
      conditions. Cycles were repeated every 21 days, and restaging was performed after
      4 cycles of therapy. In case of complete remission, 2 further cycles were
      administered for consolidation while patients achieving partial remission or
      stable disease after restaging were given 4 further courses. RESULTS: A total of
      170 cycles were administered to our patients (median 6, range 2-8). Twenty of the
      26 patients (77%) achieved a complete remission and 6 (23%) a partial remission.
      Toxicities were mainly haematological, with WHO grade III/IV leukocytopenia
      occurring in 5 patients. After a median follow-up of 19 months (range 10-45), all
      patients are alive: 22 are in ongoing remission, while 4 have relapsed between 12
      and 19 months after treatment. CONCLUSIONS: Our data demonstrate a high activity
      of R-CHOP/R-CNOP in relapsing MALT lymphoma irrespective of prior therapy.

PMID- 17220640
TI  - DNA image cytometry is a useful adjunct tool in the prediction of disease outcome
      in patients with stage II and stage III colorectal cancer.
AB  - BACKGROUND: We assessed the prognostic value of the nuclear DNA content measured
      in the primary tumours of 123 patients with stage II or stage III colorectal
      cancer (CRC). METHODS: Isolated nuclei from paraffin sections were stained with
      the Feulgen reaction, and DNA was measured using a computer-assisted image
      analysis cytometry system. We applied 4 different approaches in the analysis of
      DNA histograms: the ABCDE approach, histogram range, peak evaluation and DNA cut
      off values. RESULTS: Using the histogram range, the narrow range was rare (3.7%)
      in patients who died of disease (n = 28) as compared with 16.4% among those alive
      (n = 74; p = 0.017). Modal peak evaluation was a significant predictor of disease
      free survival (DFS; Kaplan-Meier log-rank p = 0.0235). In the range evaluation,
      the 1st set (low-start gates) was a significant predictor of DFS (log-rank p =
      0.0121), where disease recurrence was closely associated with the widest range
      (1.8->10c; c = haploid DNA content) gates. Recurrence-free survival was 3 times
      better in narrow-gate histograms than wide-range histograms (p < 0.03). The 1st
      set also proved to be a significant predictor of disease-specific survival (DSS;
      log-rank p = 0.0045), which was markedly better (77.8-90.0%) among the patients
      with the narrow-gate histograms. Grading of the histogram range into 2 categories
      (with 6.0c as cut-off), was a powerful predictor of both DSS (log-rank p =
      0.0092) and 5-year DFS (p = 0.0106) in the whole series, and separately in stage
      III (but not stage II) disease, with p = 0.0131 and p = 0.0201, respectively.
      CONCLUSION: The DNA image cytometry with careful analysis of the histograms may
      provide valuable prognostic information in CRC, with potential clinical
      implications in patient management, particularly in predicting the patients at
      high risk for recurrence who should be considered as candidates for adjuvant
      therapy.

PMID- 17220641
TI  - Combination of multiple mRNA markers (PTTG1, Survivin, UbcH10 and TK1) in the
      diagnosis of Taiwanese patients with breast cancer by membrane array.
AB  - OBJECTIVE: Early detection is a prerequisite to the effective reduction of
      morbidity and mortality from breast cancer. The present study intended to employ
      a high-throughput membrane array to detect a panel of mRNA markers expressed by
      circulating tumor cells (CTCs) in the peripheral blood of female patients with
      breast cancer. METHODS: Peripheral blood was sampled from 92 breast cancer
      patients and 100 normal persons. CTCs were detected by using a membrane array
      technique. The markers used included the pituitary tumor transforming gene 1,
      survivin, UbcH10 and thymidine kinase 1. RESULTS: The results showed that the
      membrane array could positively detect 5 cancer cells per 1 ml of peripheral
      blood in breast cancer cell dilution experiments. For the panel of 4 mRNA
      markers, sensitivity and specificity were elevated up to 86 and 88%,
      respectively. Furthermore, it was found that the patients' clinicopathological
      characteristics tumor size (p = 0.006), histologic grade (p = 0.012), lymph node
      metastasis (p = 0.001) and TNM stage (p = 0.006) significantly correlated with
      the positive detection rate of the multimarker panel. CONCLUSIONS: These findings
      demonstrated that our multimarker membrane array method could detect CTCs in the
      circulation of breast cancer patients with considerably high sensitivity and
      specificity.

PMID- 17220642
TI  - [Arthroscopic treatment of type 2 superior labrum anterior posterior lesions].
AB  - OBJECTIVES: We retrospectively evaluated patients who underwent arthroscopic
      repair for isolated type 2 superior labrum anterior posterior (SLAP) lesions.
      METHODS: Isolated type 2 SLAP lesions were treated with arthroscopic repair with
      suture anchors in eight patients (5 males, 3 females; mean age 48.5 years; range
      27 to 60 years) with shoulder pain unresponsive to conservative treatment. The
      mean duration of symptoms was 18.6 months (range 2 to 48 months). Initial
      diagnoses were based on patients' complaints and findings of physical examination
      and radiologic imaging, and were confirmed at diagnostic arthroscopy. Two suture
      anchors were used in six patients. Patients were evaluated with physical
      examination, radiographs, and the UCLA (University of California at Los Angeles)
      score. The mean follow-up was 30.8 months (range 14 to 48 months). RESULTS: The
      mean preoperative and postoperative UCLA scores were 13.3 (range 10 to 18) and
      30.8 (range 24 to 33), respectively (p<0.05). The results were good in seven
      patients (87.5%), and fair in one patient (12.5%). The mean preoperative active
      forward elevation was 136.3 degrees (range 90 degrees to 170 degrees), adduction
      external rotation was 42.5 degrees (range 40 degrees to 60 degrees), and
      adduction-internal rotation was at T7 in three patients, and at L1 in five
      patients. At final follow-ups, the mean active forward flexion increased to 164.3
      degrees (range 150 degrees to 170 degrees), adduction-external rotation was 40
      degrees (range 30 degrees to 60 degrees), and adduction-internal rotation was at
      T7 in four patients, and at T12 in four patients. CONCLUSION: The results of
      arthroscopic fixation of type 2 SLAP lesions with suture anchors are successful
      in the majority of patients, provided that an appropriate arthroscopic technique
      is performed to re-establish the stability of the biceps anchor.

PMID- 17220643
TI  - [The results of calcaneal lengthening osteotomy for the treatment of flexible pes
      planovalgus and evaluation of alignment of the foot].
AB  - OBJECTIVES: We evaluated the results of calcaneal lengthening using the modified
      Evans osteotomy technique in patients with flexible pes planovalgus and the
      effectiveness of this technique in restoring the alignment of the foot. METHODS:
      Calcaneal lengthening osteotomy was performed using the modified Evans technique
      in 22 feet of 11 patients (6 males, 5 females; mean age at the end of follow-up,
      10 years 10 months; range 5 years 6 months to 14 years 8 months) with flexible
      pes planovalgus deformity. Etiologies were cerebral palsy (n=5), sequela of
      myelomeningocele (n=1), and sensorimotor polyneuropathy (n=1); four patients were
      evaluated as idiopathic. All the patients received long-term conservative therapy
      preoperatively, and, except for one patient, none had undergone surgery for the
      deformity. All patients but one were operated on bilaterally at a single session.
      Clinical assessment was based on 10 parameters, and radiographic assessment was
      based on seven parameters on standard anteroposterior and lateral radiographs.
      The mean follow-up was 18 months (range 13 to 75 months). RESULTS:
      Radiographically, union was achieved in all the patients after a mean of seven
      weeks (range 6 to 8 weeks). Clinical results were perfect in 17 feet (77.3%),
      good in three feet (13.6%), fair in one foot (4.6%), and poor in one foot.
      Radiographically, five feet (22.7%), 13 feet (59.1%), and four feet (18.2%) were
      assessed as perfect, good, and fair, respectively. An average of 7.3 mm (range 4
      to 9 mm) of calcaneal lengthening was obtained (p<0.05). Malpositioning of the
      graft or overcorrection did not occur. Before surgery, five patients could walk
      on the heel with (n=3) or without (n=2) support; postoperatively, all the
      patients but one could perform this without support. CONCLUSION: Calcaneal
      lengthening osteotomy for symptomatic pes planovalgus provides pain relief and
      significant clinical and radiographic correction in the hind foot and forefoot.

PMID- 17220644
TI  - [Seroprevalences of hepatitis B, hepatitis C, and HIV in patients admitted to
      orthopedic and traumatology department].
AB  - OBJECTIVES: Orthopedic surgeons are at a higher occupational risk for blood-borne
      infections because of frequent handling of sharp instruments and bone fragments.
      We investigated the seroprevalences of hepatitis B, hepatitis C, and human
      immunodeficiency virus (HIV) among patients treated at orthopedic and
      traumatology department. METHODS: Data on age, sex, diagnoses, and the
      seroprevalences of HBsAg, anti-HCV and anti-HIV were reviewed in 1,040 patients
      hospitalized between September 2003 and December 2004. The patients were divided
      into two groups as orthopedics (n=646; mean age 37.8 years) or trauma (n=394;
      mean age 38.3 years) according to the initial cause of presentation. The results
      were compared with those of 28,642 blood donations during the same period.
      RESULTS: HBsAg positivity was similar in the patients (2.3%) and the controls
      (2.1%). HBsAg was detected in 16 patients (2.5%) in the orthopedics group and
      eight patients (2%) in the trauma group (p>0.05), three of whom were younger than
      one year. Similarly, the prevalences of anti-HCV antibodies were similar in the
      patient (0.6%) and control (0.3%) groups. Four patients (0.6%) in the orthopedics
      group and two patients (0.5%) in the trauma group were positive for anti-HCV
      (p>0.05), and all had a past history of operations. Anti-HIV positivity was not
      detected in the patient group, whereas it was 0.2% in the control group.
      CONCLUSION: The similarities between patients admitted to orthopedic and
      traumatology department and blood donors in the prevalences of HBsAg, and anti
      HCV and anti-HIV antibodies suggest that data obtained from blood banks can be
      used for risk calculations.

PMID- 17220645
TI  - [Arthroscopic treatment of symptomatic loose bodies in osteoarthritic elbows].
AB  - OBJECTIVES: We evaluated functional and clinical results of patients who
      underwent arthroscopic surgery for symptomatic loose bodies in osteoarthritic
      elbow joint. METHODS: Arthroscopic surgery was performed in 10 patients (6 males,
      4 females; mean age 47 years; range 30 to 59 years) for symptomatic loose bodies
      in osteoarthritic elbow joint. Eight patients had a history of trauma.
      Involvement was on the right in seven patients, and on the left in three
      patients. Preoperatively, six patients had limited joint movements and locking,
      and five patients had pain. The presence and the number of loose bodies were
      investigated by standard radiographs and computed tomography preoperatively, and
      by radiographs and magnetic resonance imaging postoperatively. The range of
      motion was measured with a goniometer. Functional assessment was made with the
      use of the Broberg and Morrey's scoring system, and pain was assessed with a
      visual analog scale. The mean follow-up was 31 months (range 7-59 months).
      RESULTS: The mean range of motion of the elbows increased from 100 degrees (range
      55 degrees to 160 degrees) preoperatively to 115 degrees (range 70 degrees to 160
      degrees) at the end of the follow-up (p=0.05). None of the patients developed
      valgus or varus instability. The mean preoperative and postoperative Broberg and
      Morrey's scores were 59 (range 45 to 80) and 86 (range 59 to 100), respectively
      (p<0.01). The results were excellent in five patients, good in three patients,
      and poor in two patients. The mean visual analog score decreased from 7 (range 5
      to 10) preoperatively to 1 (range 0-4) postoperatively (p<0.01). Eight patients
      were satisfied with surgery and returned to normal activities after a mean of 16
      days (range 1 to 60 days). CONCLUSION: Arthroscopic surgery is effective in
      reducing pain in selected patients with symptomatic loose bodies in
      osteoarthritic elbows, with the advantages of low morbidity and rapid functional
      recovery.

PMID- 17220646
TI  - [Knowledge and attitude of nursing and midwifery college students on
      developmental dysplasia of the hip].
AB  - OBJECTIVES: It is of special importance to educate families and health care
      providers, in particular midwives and nurses who are in close and frequent
      contact with families, for the prevention and early diagnosis of developmental
      dysplasia of the hip (DDH). A knowledge and attitude study was conducted
      concerning DDH among students of Nursing and Midwifery College of Kahramanmaras
      Sutcu Imam University. METHODS: A structured form was prepared consisting of 28
      statements about medical and practical knowledge and traditional attitudes with
      regard to DDH and was administered to 232 voluntary students before and after an
      educational session of 60 minutes by a specialist in orthopedics. Prior to the
      study, the students of grade I and II had not received any theoretical or
      practical lectures about DDH, which were included in the curriculum of grades III
      and IV. RESULTS: The knowledge of the students about risk factors and prevention
      strategies for DDH was of a moderate level. They were not sufficiently furnished
      with information about traditional attitudes and applications that predispose
      infants to DDH. The mean test scores before and after training were 51.52+/-13.90
      and 87.86+/-5.90, respectively (p=0.000). Compared to grade III and IV students,
      grade I students performed significantly less in the former test (p=0.00);
      however, the scores of the latter test did not differ significantly between the
      grades (p>0.05). CONCLUSION: The curriculum during the license education of
      midwives and nurses should include essential information on traditional
      attitudes. With sufficient knowledge and application skills, midwives and nurses
      may play an important role in the primary and secondary prevention of DDH in our
      country.

PMID- 17220647
TI  - [The frequency and distribution of fractures in children presenting to the
      emergency service].
AB  - OBJECTIVES: We investigated the frequency and distribution of childhood fractures
      seen at the emergency service of Tepecik Education and Research Hospital, Izmir,
      Turkey. METHODS: This prospective study included fractures of 1,706 children (992
      boys, 714 girls; age range 0 to 14 years) who presented to the emergency
      department on even-numbered days. Data forms including information about
      characteristics of the patients and fractures were filled in for each case. Age
      and sex of the patients, date and time of fractures together with mechanism,
      site, and type were recorded. RESULTS: The most frequent ages for fractures were
      7 (9%) and 3 (8%) years for boys, and 4 (9%) and 5 (8.5%) years for girls. The
      most common cause was domestic accidents (53%), followed by school (22%), traffic
      (17%), and sport (8%) accidents. Fractures occurred most frequently in summer
      (35%) especially in July, followed by autumn (24%), winter (21%), and spring
      (20%). The most frequent time intervals of presentation were between 16 and 20
      hours (32%) and between 20 and 24 hours (25%). The most common site of
      involvement was the distal radius (26%), followed by the elbow (19%), forearm
      (17%), hand-foot (12%), clavicle (9%), tibia (7%), and the femur (6%). The
      humerus (1%) was the least affected site. Treatment included conservative methods
      in 84%, and surgical methods in 16%. CONCLUSION: In our area, child fractures
      generally result from falls in summer and spring months and at play hours and are
      generally treated with conservative methods. Distal radius fractures are the most
      frequent and, inconsistent with the relevant literature data, occur at younger
      ages.

PMID- 17220648
TI  - [Thumb duplication: an analysis of 72 thumbs].
AB  - OBJECTIVES: The aim of this study was to evaluate patients who were operated on
      for a duplicated thumb. METHODS: Sixty-seven patients (41 females, 26 males; mean
      age 2.5 years; range 6 months to 20 years) underwent surgery for a total of 72
      duplicated thumbs between 1982 and 2003. Five patients had bilateral involvement.
      The anomaly was on the right in 39 cases, and on the left in 33 cases. Clinical
      and radiographic evaluations were made according to the Wassel classification.
      The Bilhaut-Cloquet technique was used in 13 symmetrically duplicated thumbs,
      while simple excision of the unserviceable part was performed in the remaining.
      Patient satisfaction was assessed with the use of a visual analog scale after a
      mean follow-up period of 3.6 years (range 1 to 10 years). RESULTS: Nail deformity
      was present in all cases treated by the Bilhaut-Cloquet technique. These thumbs
      did not exhibit growth retardation, but interphalangeal joint motion was limited
      in five, while seven had a larger size compared to the normal side. Limited range
      of motion was detected in eight cases (11.9%), affecting the metacarpophalangeal
      joint in one, and the interphalangeal joint in the others. Seventeen patients
      (25.4%) developed an angulation of more than 10 degrees in the alignment of the
      thumb. Secondary procedures were necessary in 25 cases (37.3%), including
      collateral ligament reconstruction (n=12; 17.9%), tendon rerouting (n=3; 4.5%),
      corrective osteotomy (n=5; 7.5%), and arthrodesis of the interphalangeal joint
      (n=5; 7.5%). Patient satisfaction with the surgical outcome was 85% (n=57).
      CONCLUSION: It is important to evaluate and treat the skin, nail, bone, and the
      ligaments in a simultaneous manner in order to obtain a good reconstruction and
      to decrease both the complications and the need for subsequent operations.

PMID- 17220649
TI  - [Evaluation of pediatric patients with traumatic hip dislocation].
AB  - OBJECTIVES: We evaluated pediatric patients who were treated for traumatic
      dislocation of the hip. METHODS: Traumatic dislocation of the hip was detected in
      five children (all boys; mean age 9 years; range 7 to 13 years) between 1991 and
      2005. Dislocations occurred in the right hip in four cases, and in the left hip
      in one, all of which had posterior localization. Etiology was fall during play in
      two children, and fall from height or car crash in three. One patient had
      posterior wall avulsion fracture of the acetabulum. Early radiologic follow-ups
      included conventional radiographs and computed tomography. Functional results
      were assessed with the Harris hip scoring system. Four patients had a sufficient
      follow-up period with a mean of 44 months (range 19 to 64 months). RESULTS: All
      the patients were treated with closed reduction under general anesthesia after a
      mean of 6.4 hours (range 2 to 16 hours) following trauma. Functional results were
      excellent in all the patients, with a mean Harris hip score of 92 (range 84 to
      96). Based on early postoperative radiologic control with computed tomography, no
      surgical intervention was considered for posterior wall avulsion fracture of the
      acetabulum in one patient. At 40-month follow-up, he had no complaints, had a
      full range of motion and a hip score of 92. While no complications were observed
      in patients undergoing early reduction, one patient whose dislocation was reduced
      16 hours after trauma developed avascular necrosis of the femur head 18 months
      after treatment, at which time his hip score was 84. CONCLUSION: Early reduction
      is of particular importance for the follow-up course of traumatic hip
      dislocations in childhood.

PMID- 17220650
TI  - [Assessment of the vulnerability of the proximal tibiofibular joint to injury
      during osteotomies].
AB  - OBJECTIVES: We evaluated the dimensions and anatomic localization of the proximal
      tibiofibular joint (PTFJ) in human cadaver and amputated knees. In addition, we
      assessed the relation between the osteotomy line and the PTFJ and its
      vulnerability to injury on radiographs of patients after proximal tibial medial
      open wedge osteotomy (PT-MOWO). METHODS: In the first phase, dimensions of the
      tibial part of the PTFJ lying between the lateral tibial condyle and the fibular
      head were measured by digital calipers in six human cadaver and six fresh amputed
      tibiae (4 females, 8 males; mean age 57 years) to evaluate the relation between
      the tibial surface of the PTFJ and the posterior part of the lateral tibial
      plateau. In the second phase, anteroposterior, lateral, and medial oblique
      radiographs were assessed with respect to the relation of the osteotomies with
      the PTFJ following PT-MOWO in 46 knees of 44 consecutive patients (38 females, 6
      males; mean age 51 years). RESULTS: On cadaver and fresh amputation materials,
      the mean long and short axis dimensions of the ellipsoidal articular surface of
      the PTFJ in the posterolateral aspect of the tibial plateau measured 18.8 mm
      (range 13 mm to 20 mm) and 14.9 mm (13 mm-17 mm), respectively. The upper
      articular border lied at a mean of 6.3 mm (2 mm to 11 mm) distal to the posterior
      border of the articular surface of the lateral tibial plateau. Medial oblique
      radiographs showed that the osteotomy line extended to the PTFJ in cases in which
      it was proximally located, particularly in three cases (6.5%) where lateral
      cortex continuity was interrupted. CONCLUSION: The osteotomy line may encroach
      upon the PTFJ unless preoperative oblique radiographs are evaluated and a
      parallel course to the tibial slope of the lateral tibial plateau is followed. In
      addition, insufficient evaluation of PT-MOWO candidates may result in damage to
      the lateral cortex, which increases the risk for injury to the PTFJ.

PMID- 17220651
TI  - [An unusual cause of hip pain: pelvic granulocytic sarcoma].
AB  - A 27-year-old male patient presented with right-sided hip pain. Magnetic
      resonance imaging of the hip joint revealed an extensive intrapelvic mass
      adjacent to the iliopsoas muscle. Laboratory tests showed severe leukocytosis and
      a differential WBC count enabled the diagnosis of chronic myeloid leukemia (CML).
      The pelvic mass was then assessed as granulocytic sarcoma developing from CML. It
      should be kept in mind that the initial presenting feature of hematological
      diseases such as CML may be hip pain arising from CML-associated granulocytic
      sarcoma.

PMID- 17220652
TI  - [An analysis of genetic transmission in a father and son with osteosarcoma].
AB  - Familial osteosarcoma is a rare hereditary disease. We present a 37-year-old
      father and a 17-year-old son who developed osteosarcoma in the left and right
      distal femurs, respectively, at a three-year interval. They were treated with
      chemotherapy followed by surgery. Both had positive immunostaining for p53 tumor
      suppressor gene and HER-2/neu oncogene. The son also exhibited deletion of the
      retinoblastoma 1 gene. Pulmonary metastasis was detected in the father at the
      time of diagnosis and 13 months after primary treatment, whereas no distant
      metastasis was present in the child. The father died 39 months after the
      diagnosis from primary symptoms, but the son led a disease-free survival a year
      after completion of treatment. Genetic abnormalities documented in the father and
      son corroborate the presence of specific genetic alterations in the pathogenesis
      of osteosarcoma.

PMID- 17220653
TI  - [Atraumatic bilateral patellar tendon rupture in a patient receiving steroid
      therapy].
AB  - Atraumatic bilateral patellar tendon rupture is a rare entity. It is usually due
      to systemic or local disorders causing tendon degeneration. Early diagnosis and
      surgical treatment are crucial for recovery of knee functions. Atraumatic
      bilateral patellar tendon rupture was diagnosed in a 31-year-old female patient
      who had been receiving steroid therapy for seven years due to systemic lupus
      erythematosus. She underwent patellar tendon reconstruction with the use of
      semitendinosus and gracilis tendons. After a follow-up of six months, she could
      walk without crutches and had a full range of motion.

PMID- 17220654
TI  - [Petrous bone lesions].
AB  - OBJECTIVES: We evaluated the results of treatment and follow-up of patients with
      petrous bone lesions. PATIENTS AND METHODS: We retrospectively evaluated 13
      patients (5 females, 8 males; mean age 33.8+/-17.4 years; range 4.5 to 65 years)
      who were treated and followed-up for petrous bone lesions between 1990 and 2004.
      The diagnoses were cholesterol granuloma (n=2; 15.4%), chondrosarcoma (n=1;
      7.7%), and cholesteatoma (n=10; 76.9%). RESULTS: Patients with cholesterol
      granuloma had complaints of cephalgia and diplopia while those with cholesteatoma
      complained of otorrhea and hearing loss. One patient with cholesterol granuloma
      and eight patients with cholesteatoma underwent surgical operations with the use
      of middle skull base approach (n=1), transcochlear approach (n=2),
      translabyrinthine approach (n=1), and tympanopetrosectomy (n=5). Two cases with
      congenital cholesteatoma and one patient with cholesterol granuloma refused
      surgical intervention and were only followed-up. CONCLUSION: Besides surgical
      intervention, follow-up by computed tomography or magnetic resonance imaging may
      be considered in patients with incidental petrous bone lesions, presenting with
      limited symptoms.

PMID- 17220655
TI  - Experimental autogenous cartilaginous grafts for laryngotracheoplasty: a
      comparison of two techniques and two different types of grafts.
AB  - OBJECTIVES: This experimental work was performed to compare the results of
      laryngotracheoplasty with the use of autogenous cartilaginous grafts harvested
      either from the auricula or costal cartilage using two techniques, anterior or
      posterior graft placement. STUDY DESIGN: This study was carried out in 20 healthy
      dogs of both sexes and varying ages, weighing about 12-15 kg. The animals were
      divided into two groups (A and B), equal in number. We used costal cartilage
      grafts in group A, and auricular cartilage grafts in group B. The anterior and
      posterior laryngeal walls were vertically divided and the cartilage grafts were
      sutured in place. RESULTS: Microscopic examination of laryngeal specimens showed
      a higher rate of graft displacement in group B (40% vs 20%) and in those placed
      posteriorly (50% vs 10%) (p<0.05). Auricular cartilages showed more resorption
      and degeneration than costal cartilages. Severe to complete resorption was
      detected in 30% in group B, which was twice as much in anteriorly placed grafts,
      whereas no resorption occurred in group A. CONCLUSION: The use of auricular
      grafts and posterior placement was significantly associated with more graft
      displacement.

PMID- 17220656
TI  - Karyometric analysis of nasal polyps.
AB  - OBJECTIVES: Nuclear characteristics of epithelial cells in nasal polyps were
      analyzed. PATIENTS AND METHODS: The slides of 35 patients who underwent surgery
      for nasal polyposis and 18 slides of normal mucosa were examined. The specimens
      were stained with hematoxylin-eosin. Tissue sections were analyzed by a CCD
      camera and the Karyotype Program of Human Cytogenetics Nomenclature System on a
      Macintosh computer (OS 9). Fifty epithelial cells in each slide were randomly
      selected and transferred to the automated karyotyping system and photographed.
      The diameters of the nuclei were measured and some peculiar nuclear features were
      examined, including unsmooth appearance of the nuclear membrane, anaphase-bridge,
      and binucleation. RESULTS: There were significant differences between nasal polyp
      and normal mucosa groups in terms of nuclear diameter, perimeter, and volume,
      with all variables being greater in the nasal polyp group (p=0.001). Unusual
      nuclear features differed significantly (unsmooth nuclear membrane appearance,
      p<0.001; anaphase-bridge, p=0.041; binucleation, p=0.018), as well. CONCLUSION:
      Epithelial cells of nasal polyps exhibit nuclear instability.

PMID- 17220657
TI  - [Comparison between tympanoplasties with cartilage-perichondrium composite graft
      and temporal fascia graft in terms of hearing levels and healing].
AB  - OBJECTIVES: We compared the extent of healing and hearing improvement following
      tympanoplasties performed with the use of cartilage-perichondrium composite
      grafts and temporalis muscle fascia grafts. PATIENTS AND METHODS: Fifty
      consecutive patients (22 males, 28 females; mean age 30+/-14 years; range 11 to
      63 years) with chronic otitis media were divided into two groups to receive
      cartilage-perichondrium composite grafts or temporal muscle fascial grafts. All
      the patients were evaluated by pure-tone audiometry and otomicroscopic
      examination in the 1st, 3rd, 6th, and 12th months. RESULTS: At the end of the
      first year, graft survival was 92% in the cartilage group, and 85% in the fascia
      group. Hearing levels improved at the end of the first year; however, the two
      groups did not differ significantly in terms of hearing improvement and graft
      survival. Hearing gains were greater in central and subtotal perforations. In
      comparison with a steady increase in the cartilage group, hearing levels remained
      unchanged after the sixth month in the fascia group. CONCLUSION: Cartilage
      perichondrium composite grafts may be easily and safely used in type I
      tympanoplasties, with successful results including hearing improvement.

PMID- 17220658
TI  - [Frontoethmoidal sinus mucocele as a rare finding in a patient with craniofacial
      fibrous dysplasia].
AB  - Fibrous dysplasia is a benign developmental skeletal disorder characterized by
      bony expansion secondary to replacement of the medullary cavity by fibroosseous
      connective tissue. A 16-year-old male patient underwent magnetic resonance
      imaging for headache, left proptosis, and a thrill over the left temporal artery.
      T1- and T2-weighted images showed extensive bone involvement of typical low
      signal intensity in the left hemicalvarium, skull base, and facial bones. Another
      striking finding was the presence of a frontoethmoidal sinus mucocele, which
      demonstrated high signal intensity both on T1- and T2-weighted images. The
      diagnosis was made as fibrous dysplasia after bone biopsy and histopathological
      evaluation.

PMID- 17220659
TI  - [Iatrogenic nasal meningocele: a cause of recurrent meningitis].
AB  - We present a 35-year-old male patient with an eight-year history of endoscopic
      nasal polypectomy followed by five episodes of meningitis (4 episodes in the past
      3 years). His major complaints were right-sided nasal obstruction, frequent
      watery nasal discharge, headache, and fever. Physical examination revealed a mass
      in the right nasal cavity. Computed tomography and magnetic resonance imaging
      demonstrated a defect in the cribriform plate and an ethmoidal meningocele. The
      patient was referred to the neurosurgery department for surgical reparation.

PMID- 17220660
TI  - Endonasal approach for frontobasal malignant nerve sheath tumor: a case report.
AB  - Malignant peripheral nerve sheath tumors (MPNST) are rarely encountered in the
      paranasal sinuses and frontal skull base. We present histopathological findings,
      cytometric DNA measurements, and the preliminary results of comparative genomic
      hybridization analysis of a 46-year-old male patient with a frontobasal MPNST.
      The tumor was resected via the endonasal approach. No tumor recurrence was
      detected during a follow-up of three years. Rhinologists are being more
      frequently involved in endonasal tumor resection.

PMID- 17220661
TI  - [Molecular mechanism and potential targets for bone metastasis].
AB  - The incidence of bone metastasis has been increasing in all cancers in recent
      years. Bone metastasis is associated with substantial morbidity, including bone
      pain, pathological fracture, neurological deficit and/or hypercalcemia. Thus, the
      management of bone metastasis in patients is a clinically significant issue. In
      the process of bone metastasis, the primary mechanism responsible for bone
      destruction is cancer cell-mediated stimulation of osteoclastic bone resorption,
      which results in osteolysis and release of various growth factors from the bone
      matrix. These growth factors are prerequisites for successful colonization and
      subsequent invasive growth of cancer cells in bone, which is called a "vicious
      cycle." Thus, it is important to elucidate what molecules are involved in this
      step of bone destruction, and the understanding of these molecular mechanisms
      could lead to develop molecular-target therapies for bone metastasis.
      Bisphosphonates introduced in the treatment for bone metastasis have been shown
      to reduce skeletal morbidity. In Japan, the most potent bisphosphonate,
      zoledronate (ZOMETA), was introduced in this past April, and a phase III clinical
      trial of humanized anti-RANKL monoclonal antibody (Denosumab) against bone
      metastasis is under way as a global study. These new agents, which are targeted
      to osteoclasts, are considered to be standard management in the care of bone
      metastasis patients in combination with chemotherapy and/or hormone therapy.

PMID- 17220662
TI  - [Gastric cancer and eradication of H. pylori].
AB  - Diagnosis and treatment of gastric cancer has now been established, and
      prevention is thought to be of importance to overcome this disease. Many
      experimental and clinical researches have clarified the pivotal role of H. pylori
      infection in gastric carcinogenesis. Therefore, prevention of gastric
      carcinogenesis by H. pylori eradication seems to be promising, and the
      possibility has been suggested by experimental and clinical studies. The issues
      to be solved are to select the candidates for eradication and to assess the
      timing of eradication. Development of new diagnostic methods and biomarkers for
      H. pylori eradication is required.

PMID- 17220663
TI  - [Endoscopic resection for early gastric cancers by EMR/ESD].
AB  - The key issue in the field of therapeutic endoscopy in recent years is the
      development of a new therapeutic strategy for early gastric cancers using
      endoscopic submucosal dissection (ESD) technique. ESD was developed to overcome
      the problem of remnant or recurrent tumors after incomplete resection by
      conventional endscopic mucosal resection (EMR). Ever since after the emergence of
      ESD, indication criteria for endoscopic resection of early gastric cancers were
      extended through expansion of both theoretical and technical conditions. Complete
      en bloc resection rates were 96.7% and 62.6% in the ESD group and the EMR group,
      respectively, in our institution. ESD is a highly effective technique enabling us
      to resect much larger and difficult lesions, which cannot be resected by
      conventional EMR techniques. However, it involves a much higher complication rate
      and requires much higher skills. A small lesion less than 20 mm located in a good
      position can be resected completely, without any difficulties using conventional
      EMR techniques. Therefore, we must consider the approach to treatment, when
      conducting an endoscopic resection,it terms of the situation and skills of the
      endoscopist.

PMID- 17220664
TI  - [The advances of laparoscopic treatment for gastric cancer].
AB  - Recently, laparoscopic surgery for gastric cancer is very interesting topic in
      the treatment of gastric cancer. Therefore,many surgeons are attempting
      laparoscopic surgery. However, the technique of this surgery has never been
      established yet. From July 1997 to July 2006, we performed laparoscopic surgeries
      for 420 cases of gastric cancer with lymph node dissection. We have describe our
      technical advances in laparoscopic treatment for gastric cancer along with the
      clinical outcomes.

PMID- 17220665
TI  - [Evaluation of the preserved function of the remnant stomach in pylorus
      preserving-gastrectomy by gastric emptying scintigraphy].
AB  - This study evaluated the preserved function of the remnant stomach by gastric
      emptying scintigraphy 1 year postoperatively in 49 patients who underwent pylorus
      preserving gastrectomy (PPG), and it investigated whether this examination method
      is a useful tool for evaluation. The residual stomach function was classified as
      rapid, intermediate, and delayed emptying types according to gastric emptying
      curves. Then, the relationships were examined between the gastric emptying types
      and postprandial symptoms, food intake status, body weight changes, and
      endoscopic findings. Seventy-three percent of the PPG patients were classified as
      belonging to the intermediate emptying type, and the remainder (27%) to the
      delayed type. The frequencies of complaints such as epigastric fullness, nausea,
      and vomiting were high in the delayed emptying-type patients. The intermediate
      emptying-type patients consumed larger amounts of food and gained more weight
      than the delayed emptying-type patients. In conclusion, gastric function was
      evaluated by gastric emptying scintigraphy in PPG patients. This method might be
      useful not only for evaluating the motor function of the remnant stomach, but
      also for predicting postoperative status. Although PPG is a function-preserving
      operation, it should be considered that a quarter of the patients showed delayed
      emptying type which related to poor quality of life.

PMID- 17220666
TI  - [Chemotherapy in advanced gastric cancer--to ensure timely and appropriate switch
      to subsequent treatment options].
AB  - Since irinotecan, S-1, docetaxel, and paclitaxel were approved, therapeutic
      options for chemotherapy in the treatment of gastric cancer have increased. It is
      suggested that the efficient use of the primary drugs prolongs life in the
      treatment of progressive colorectal cancer. Also, physicians have discussed ways
      to take full advantage of the drugs in the treatment of gastric cancer. In first
      line treatment in other countries, combination therapy usually includes the
      administration of two drugs, while in Japan, where therapies based on S-1 have
      been developed, the most appropriate strategy must be determined after reporting
      the results of phase III trials in 2007. In the clinic, treatment must be
      selected on the basis of solid evidence in consideration of the organ dysfunction
      associated with progressive gastric cancer. The timing of any changes in the
      treatment should be considered because the cancer easily metastasizes to the
      peritoneum. Throughout the world, various regimens have been developed that
      replace cisplatin with oxaliplatin or mainly use oral fluoropyrimidine. Molecular
      target drugs, now being evaluated in phase II trials, will also be used in the
      treatment of gastric cancer in the near future. Novel therapies will be developed
      in Asia and Japan where the incidence of gastric cancer is high.

PMID- 17220667
TI  - [Diagnostic procedure combination in gastric cancer treatment].
AB  - Present status and problems in diagnostic procedure combination (DPC) for
      treatment of gastric cancer are reviewed in this article. DPC for gastric
      malignancies are subgrouped by the presence or absence of operation, operative
      procedures and adjuvant treatment such as intensive care, radiotherapy and
      chemotherapy. In a comparison between prospective payment and medical cost
      invested, most investments can be recovered by DPC in patients who underwent
      mucosal resection or gastrectomy without major complications. However, in
      patients with postoperative complications who required intensive
      treatment,considerable investments can not be recovered by DPC. In patients given
      chemotherapy, most of the investments in conventional chemotherapy can be
      recovered by current DPC. The clinical pathway appears to be a useful tool to
      control homogeneously well-qualified investments in DPC.

PMID- 17220668
TI  - [Phase I/II clinical trial of induction chemotherapy with nedaplatin (CDGP),
      docetaxel (DOC) and 5-fluorouracil (5-FU) for squamous cell carcinoma of head and
      neck].
AB  - In a phase I study, we determined the maximum tolerated dose (MTD) and the
      recommended dose (RD) of nedaplatin (CDGP) in combination chemotherapy with
      Docetaxel (DOC) and 5-fluorouracil (5-FU) for treatment of carcinoma of the head
      and neck. Then, in a phase II study, we examined the efficacy and safety of the
      RD of chemotherapy. Fresh patients with squamous cell carcinoma of the head and
      neck were enrolled in the study. The dosage of chemotherapy was as follows: DOC
      60 mg/m(2) on day 1 by infusion over 2 hours; CDGP 20-30 mg/m(2)/day on day 1 to
      5 by infusion over 1 hour, and 5-FU 600 mg/m(2)/day on day 1 to 5 by 5 days
      continuous infusion. For CDGP, an initial dose level was set at 20 mg/m(2), and 3
      patients were enrolled for each level of dose escalation. The DLT was defined
      here as grade 4 neutropenia or grade> or =3 non-hematotoxic reactions. The dose
      at which DLT was observed in overall 33% cases was taken as MTD. The RD for phase
      II study was estimated to be DOC 60 mg/m(2), CDGP 20 mg/m(2)/day, 5-FU 600
      mg/m(2)/day. Forty patients were enrolled in the phase II study. DLT of
      neutropenia was noted in 2 of 38 cases. DLT of non-hematotoxic reactions was
      found in less than 33% of the cases; 17 cases showed CR, and 12 cases showed PR.
      The response rate was 76.3%. The overall response rate in histological assessment
      was 55.3%. The combination chemotherapy with Low-Divided Dose of CDGP, DOC and 5
      FU was suggested to be safe and effective.

PMID- 17220669
TI  - [Evaluation of docetaxel, CDDP and 5-FU combined therapy as second-line
      chemotherapy for esophagus cancer].
AB  - The combined therapy of docetaxel (70 mg/m(2), day 1), CDDP (80 mg/m(2), day 1)
      and 5-FU (800 mg/m(2), day 1-5) is used as second-line chemotherapy for esophagus
      cancer. First-line chemotherapy for 32 advanced squamous cell carcinomas of the
      esophagus is not effective, and early recurrences after chemotherapy were
      examined. Pretreatment surgery was used in 20 cases,radiation therapy in 19 and
      chemotherapy by 3.1 courses (1-9) on average. PR was found in 16 patients
      (response rate 50%) in the first course, MR in 2, NC in 6, and PD in 7 cases.
      Among 16 patients,one was discontinued due to aspiration pneumonia and two by
      leukopenia. Thirteen patients received 3-5 courses. The operation was
      continuously enforced in three patients among 13, radiation therapy was added in
      three, and they survived for one year or more. Five for whom imaging became
      virtually impossible lived for six months or more. Additional treatment proved
      ineffective in 2, so it was discontinued. There were 18 lymph node examples of
      lesions effectively treated, 6 main lesions, 1 pulmonary metastasis and 1 bone
      metastasis. As for deleterious events, leukopenia was admitted in 95%. G-CSF was
      needed by 68% during use and 3 days on average. The CDDP+5-FU+docetaxel therapy
      was comparatively safe in patients with much pre-treatment and demonstrated a
      maximum effect at more than the expected rate.

PMID- 17220670
TI  - [Stratification with respect to hormone receptor and HER 2/neu in the treatment
      of metastatic breast cancer; sensitivity to taxane].
AB  - Of 231 patients with recurrent or metastatic breast cancer treated in Hiei
      Hospital between January 2001 and March 2005, for whom data on hormone receptor
      (HR) and HER 2/neu were available, we retrospectively analyzed the association of
      the response rate with HR and HER 2 in 172 patients treated with taxane in whom
      the treatment response could be evaluated. Among the patients treated with taxane
      alone,the response rates were 37.5% (n=67) in the HR (+) patients and 14.6%
      (n=41) in the HR (-) patients (p=0.0131). In particular, taxane resistance was
      suggested in the HR (-)/HER 2 (-) patients (response rate: 4.2%, n=24).
      Concerning combination therapy with trastuzumab and taxane, the response rate
      were 52.8% in the HR (+)/HER 2 (+) patients and 60.4% in the HR (-)/HER 2 (+)
      patients. In 27 of these patients, single therapy with taxane was switched to
      combination therapy with taxane and trastuzumab after they became resistant to
      taxane, and 8.3% of the HR (+)/HER 2 (+) patients and 53.3% of the HR (-)/HER 2
      (+) patients responded to this combination therapy (p=0.0192), suggesting the
      synergistic effects of the two agents in HR (-)/HER 2 (+) patients. Therefore, HR
      and HER 2 were associated with the sensitivity to a chemotherapeutic agent,
      taxane. Stratification with respect to HR and HER 2 is important in the treatment
      of metastatic breast cancer. In particular, therapeutic strategies for HR (-)/HER
      2 (-) patients with a poor prognosis must be established in the future.

PMID- 17220671
TI  - [New porous gelatin particles for hepatic arterial embolization--investigation of
      passage through current microcatheters].
AB  - Hepatic arterial embolization (HAE) has been widely performed for unresectable
      hepatocellular carcinoma (HCC) in a selective manner using a microcatheter.
      Gelatin sponge is exclusively used as an embolic agent, though it has not yet
      been approved for an arterial blockade. Recently, new porous gelatin particles
      (GP) have been approved and are clinically available. In this study, passage of
      GP through microcatheters was investigated, as it is an important requirement for
      a new agent. Both 1-mm and 2-mm GP were injected through each of six current 2.0
      Fr-2.7 Fr microcatheters by five board-certified interventional radiologists. In
      general, use of a 2.5 mL lock syringe was associated with higher subjective
      resistance score (5-10/10), longer injection time (20-30 sec), and lower
      injection pressure (1.0-2.5 MPa) with difficulty. When it was impossible to
      inject GP with a 2.5-mL lock syringe,injection was retested with a 1 mL lock
      syringe resulting in lower resistance score (1-6), shorter injection time (6-10
      sec), and higher injection pressure (1.5-2.5 MPa) regardless of particle size.
      Thus,it is recommended to use a 1 mL lock syringe for injection of GP through a
      microcatheter. After passing through a 2.0 Fr microcatheter, 2 mm particles
      showed no significant deformation or fragmentation under observation by
      stereomicroscopy.

PMID- 17220672
TI  - [Preoperative therapy with trastuzumab and paclitaxel in a stage IV advanced
      breast cancer with complete pathologic response].
AB  - A 53-year-old woman had a 105x100 mm tumor on her right breast with a 55x36 mm
      sized bleeding ulcer of the skin and ipsilateral axillary and cervical lymph
      nodes swelling (T4bN3cM1, Stage IV). Core needle biopsy and immunohistochemistry
      of breast tumor showed invasive ductal carcinoma with negative hormone receptor
      (ER-, PgR-) and overexpression of HER 2 (Hercep Test score 3+). She was treated
      with weekly trastuzumab (initially 4 mg/kg followed by 2 mg/kg every week), and a
      combination of tri-weekly paclitaxel (175 mg/m(2), 6 courses). After 3 courses of
      administration, the breast tumor subsided, the ulcer became flat, and axillary
      and cervical nodes completely disappeared. Clinical CR was obtained after 6
      courses of treatment, and mastectomy with axillary clearance was then performed.
      Histopathology of the breast and lymph nodes showed complete disappearance of
      cancer cells (pCR, Grade 3+3 (d) +3 (n)). The combination of trastuzumab and
      paclitaxel is a promising regimen for HER 2 positive advanced breast cancer.

PMID- 17220673
TI  - [A patient with advanced breast cancer refractory to chemotherapy accompanied by
      carcinomatous pleurisy and multiple bone metastasis that responded to combination
      therapy with high-dose toremifene and docetaxel].
AB  - The patient was a 76-year-old woman, who found a mass in her left breast around
      summer of 2003 but ignored it. She visited our hospital in April 2004 because of
      dyspnea and low-back pain. As there was a mass accompanied by partial ulceration
      all over the left precordium and bilateral pleural effusion, she was admitted for
      further evaluation and treatment. The patient was judged to be almost in a life
      threatening condition, and thus thoracentesis was performed to remove pleural
      fluid, and chemotherapy with FEC was also performed. In addition, the patient was
      placed on oral exemestane (EXE). After four courses of therapy with FEC were
      completed, the drug was changed to paclitaxel (PTX) and chemotherapy was
      continued for another 3 months. It was confirmed that the tumor size had been
      reduced markedly and that the volume of pleural effusion had not increased. The
      patient was in a state of remission for a short time, but subsequently the tumor
      size increased again and the tumor bled continually in small amounts. The
      chemotherapeutic drug was changed to capecitabine, while EXE, which had been
      continued, was withdrawn and oral administration of 120 mg/day of toremifene
      (TOR) was started. However, the tumor size was not reduced. TOR was continued,
      while capecitabine was changed to docetaxel (DOC). Then, the tumor size was
      reduced again, until the breast became almost flat after 3 months and the patient
      no longer bled from the tumor. The volume of pleural effusion did not increase,
      nor did the patient have any more dyspnea. At present, she has been in a state of
      remission and is living at home with a certain QOL.

PMID- 17220674
TI  - [Locally advanced breast cancer with a good response to sequential endocrine
      monotherapy--a case report].
AB  - An 81-year-old woman with a right breast tumor exposed through the skin surface
      visited our clinic in June 2004. Pathological findings of the resected tumor
      specimen indicated invasive ductal carcinoma of the breast,positive ER/PgR
      status,and negative HER 2/neu status. The enlarged right axillary lymph nodes
      were palpable. Ultrasonography and computed tomography revealed that the tumor
      invaded the chest wall without any metastasis to remote organs. On July 5, 2004,
      we started anastrozole treatment. Its effects were confirmed in the first
      month,and the treatment was continued for 8 months. Substituting anastrozole with
      exemestane was not effective. However, the exposed part of the tumor completely
      responded to tamoxifen that was administered for 2 months. The effect of
      tamoxifen continued until February 2006, and most of the subcutaneous part of the
      tumor became nonpalpable. Thus, sequential endocrine monotherapy proved useful
      for an elderly woman with locally advanced breast cancer.

PMID- 17220675
TI  - [A case of inflammatory breast cancer achieving pathological complete response by
      primary systemic therapy with CEF (cyclophosphamide, epirubicin, 5-fluorouracil)
      followed by docetaxel].
AB  - A 48-year-old woman noticed her right breast swelling since a few weeks earlier.
      Rigidity in the AC area, hotness, swelling and peau d'orange appearance of the
      right whole breast were recognized. She was diagnosed as inflammatory breast
      cancer clinically and invasive ductal carcinoma with lymphatic invasion
      pathologically. The patient underwent primary systemic therapy with 4 cycles of
      CEF (cyclophosphamide 500 mg/m(2), epirubicin 100 mg/m(2), 5-fluorouracil 500
      mg/m(2)) followed by 4 cycles of docetaxel (70 mg/m(2)). The effect of
      chemotherapy showed a partial response evaluated by mammography and
      ultrasonography, and complete response by MRI before surgery. Right mastectomy
      with level II lymph node dissection was performed. Pathologically, complete
      response was confirmed (pCR). Although IBC has been known for its poor outcome,
      this case suggests IBC will show a better prognosis by chemotherapy such as CEF
      followed by docetaxel.

PMID- 17220676
TI  - [Superficial small cell carcinoma of esophagus treated by endoscopic mucosal
      resection combined with chemoradiotherapy--a case report].
AB  - The patient was a 70-year-old woman who was admitted to our hospital for positive
      fecal occult blood. Upper gastrointestinal endoscopy revealed a superficial
      plateau-type (0- I sep) submucosal cancer on the right wall of the esophagus 28
      cm from the incisor. Biopsy revealed small cell carcinoma. CT scan detected
      neither lymph node metastasis, nor distant organ metastasis. Endoscopic mucosal
      resection (EMR) was performed. Post-EMR chemoradiotherapies were conducted. The
      patient has lived with no evidence of cancer recurrence for 40 months. This was
      the first case of esophageal small cell carcinoma treated by EMR combined with
      chemoradiotherapy.

PMID- 17220677
TI  - [A case report of advanced gastric cancer with carcinomatous ascites successfully
      treated by outpatient chemotherapy].
AB  - The patient was a 54-year-old male with peritoneal dissemination and
      carcinomatous ascites of advanced gastric cancer. Although 4 months of temporary
      partial responses were obtained by a combination chemotherapy with TS-1 and DOC,
      retention of ascites appeared. Second-line combination chemotherapy with 5-FU and
      PTX was not effective, and we attempted to use intraperitoneal chemotherapy of
      low-dose CDDP. After 100 mg of CDDP had been administered, ascites almost
      disappeared. Then,intraperitoneal injection of low-dose CDDP and intravenous
      injection of 5-FU were given. Tumor marker decreased remarkably, and CT revealed
      reduction of peritoneal dissemination. These regimens seem to be effective in
      ambulant patients with advanced gastric cancer with peritoneal dissemination and
      carcinomatous ascites.

PMID- 17220678
TI  - [A case of stage IV gastric cancer treated sequentially for over two years by TS
      1, paclitaxel, and CPT-11].
AB  - We report a patient with advanced stage IV gastric cancer treated by chemotherapy
      for over two years. The patient was a 69-year-old man with paraaortic lymph node
      metastasis of gastric cancer. He underwent a distal gastrectomy in non-curative
      resection. After surgery, chemotherapy with TS-1 (100 mg/body/day) was performed.
      At 7 months after surgery, progression of lymph node metastasis in porta hepatis
      was recognized, and paclitaxel was administered at a weekly dose of 80 mg/m(2)
      for 3 weeks followed by one week rest. He remained stable for 12 months under
      paclitaxel treatment. At 26 months after surgery, progression of lymph node
      metastasis in porta hepatis was recognized again, and CPT-11 was administered at
      a bi-weekly dose of 80 mg/m(2). Although the patient died two years seven months
      after surgery, the chemotherapy with sequential administration of TS-1,
      paclitaxel and CPT-11 was thought to be effective for advanced gastric cancer.

PMID- 17220679
TI  - [A case of stage IV advanced gastric cancer responding to TS-1/CDDP neoadjuvant
      chemotherapy which leads to a pathological complete response].
AB  - A 72-year-old male with advanced gastric cancer (cT3N2M0H0P0CY1, cStage IV) was
      treated with TS-1/CDDP as neoadjuvant chemotherapy. TS-1 (60 mg/m(2)/day) was
      orally administered for 3 weeks followed by 2 drug free weeks as a course, and
      CDDP (60 mg/m(2)) was administered by intravenous drip on day 8. After the fourth
      course,a significant tumor reduction was obtained. Total gastrectomy,
      splenectomy, and D 2 type nodal dissection were performed. The histological
      diagnosis revealed complete disappearance of cancer cells in the stomach and all
      of the lymph nodes, which is a so-called pathological complete response. The
      patient has now been in good health without a recurrence for 24 months after
      surgery. This case suggests that neoadjuvant chemotherapy with TS-1/CDDP is a
      potential regimen for advanced gastric cancer.

PMID- 17220680
TI  - [A case of recurrent gastric cancer with obstructive jaundice successfully
      treated by docetaxel].
AB  - Recently, treatment by taxane regimen for advanced gastric cancer as second-line
      chemotherapy has been increasingly reported. A 58-year-old man underwent distal
      gastrectomy for advanced gastric cancer on November 25, 2002. There was
      permeation through the duodenum side, and a Billroth II operation was done for
      repair. Although a relapse was not clear from the picture image, due to the tumor
      marker increase since July 2004, chemotherapy using TS-1 100 mg/day was given. On
      February 2005, liver dysfunction and obstructive jaundice appeared, and the
      patient was diagnosed with a recurrence in the hilar lymph node of the liver
      through PET and CT. Because of the Billroth II operation for repair, ERBD was
      impossible, and we performed PTCD to decrease jaundice. Treatment by docetaxel 60
      mg/m(2) every three weeks was given since March 15. After two courses of
      chemotherapy with docetaxel, the insertion of the guide wire was possible from
      the part of PTCD. Implantation of the stent became possible after four courses.
      PTCD could be removed, and the patient QOL has effectively improved. Outpatient
      treatment became possible for him in January 2006.

PMID- 17220681
TI  - [Weekly paclitaxel therapy effective for gastric cancer with obstructive jaundice
      due to peritoneal dissemination--a case report].
AB  - The patient was a 61-year-old man who suffered from advanced gastric cancer, and
      a distal gastrectomy was performed (T3N2P1CY1, Stage IV). He was treated with
      chemotherapy of TS-1 alone (100 mg/day, days 1-28 with two weeks rest). Six
      months later he complained of lumbago and appetite loss, then was admitted to the
      hospital with obstructive jaundice. Total bilirubin (T-Bil) was increased to 11.3
      mg/dl. CT scan examination revealed peritoneal dissemination with much ascites
      and dilatation of intrahepatic bile ducts. Endoscopic drainage was tried, but was
      discontinued due to stenosis of gastroduodenal anastomosis. Ultimately, T-Bil was
      elevated to 25.2 mg/dl, and he could not sleep comfortably because of a severe
      itch and an irritating feeling. Weekly paclitaxel therapy was started (70
      mg/m(2), day 1, 8, 15, once a week for 3 weeks followed by a week rest as one
      cycle). One month after the first infusion therapy, the obstructive jaundice was
      notably improved and the ascites disappeared completely, so he was discharged.
      For about one year, he was treated with this chemotherapy as an outpatient. The
      toxic events were anemia (grade 3) and alopecia (grade 1).

PMID- 17220682
TI  - [Successful CPT-11 treatment in a patient with pancreatic cancer associated with
      multiple liver metastases and chronic renal failure].
AB  - A 56-year-old woman, who had been receiving treatment for chronic renal failure,
      was admitted to our Department because of a tumor of the pancreas head and
      multiple liver masses diagnosed by abdominal CT scans. Gastroduodenoscopy
      revealed a tumor which had invaded the Vater's papilla; the lesion was
      histopathologically pancreatic adenocarcinoma. Due to the presence of multiple
      metastases to the liver, we therefore performed general chemotherapy after
      obtaining the patient's informed consent (IC). CPT-11 was selected as the
      carcinostatic agent because the patient suffered from renal failure. The initial
      dose of CPT-11 was 80 mg, and we thereafter made minor adjustments in the dosage
      depending on the occurrence of side effects. After four courses of the treatment,
      a CT scan revealed both the tumor of the pancreas head and the multiple liver
      masses to have almost completely disappeared. Our clinical results indicate that
      CPT-11 may therefore be a strong candidate for first-line chemotherapy for the
      treatment of pancreatic cancer, especially in patients with renal failure.

PMID- 17220683
TI  - [A case of recurrent colon cancer with urinary bladder, para-aortic lymph nodes,
      and spleen metastases successfully treated with CPT-11].
AB  - The patient was a 71-year-old woman with sigmoid colon cancer with urinary
      bladder invasion, for which sigmoidectomy with D 3 lymphadenectomy and partial
      cystectomy was performed. After surgery, the patient was started on 4 courses of
      6-week systemic chemotherapy (500 mg/m(2) 5-FU and 200 mg/m(2) l-LV weekly).
      However, 4 months later, CT revealed local recurrence in the urinary bladder and
      recurrence in the para-aortic lymph nodes and spleen. Therefore, low-dose CPT-11
      therapy (40 mg/m(2) once per week) was instituted, which achieved a complete
      response as revealed by CT for response evaluation 5 months after the start of
      therapy. Up to the present, after 8 months no recrudescence or recurrent lesions
      in other organs have been observed. The patient developed mild side effects such
      as grade 1 nausea, anorexia, and leukopenia, but has a well-maintained QOL.

PMID- 17220684
TI  - [CR of rectal cancer and synchronous liver and lung metastases obtained with TS-1
      plus CPT-11 combination therapy--case report].
AB  - The patient was a 44-year-old male in whom low anterior resection of the rectum,
      partial pneumonectomy, and liver biopsy were performed because of suspicion of
      synchronous liver and pulmonary metastases of rectal cancer which caused familial
      adenomatous polyposis. Because anticancer drug sensitivity testing by the HDRA
      method performed on tissue collected from the cancer immediately postoperatively
      revealed sensitivity to 5-FU and CPT-11, and measurement of nucleic acid
      metabolizing enzymes showed a high level of DPD, a 5-FU metabolizing enzyme,
      combination therapy with TS-1 and CPT-11 was started. TS-1, 120 mg/body, was
      administered on 14 consecutive days followed by a 7-day rest period, and CPT-11,
      120 mg/body, was administered on day 1 and day 8. One cycle was defined as 3
      weeks,and cycles were repeated. Grade 2 diarrhea occurred, but the CPT-11 dose
      was reduced to 100 mg/body, and treatment was continued. CR was achieved when the
      4th course had been completed. Thoracic and abdominal CT was performed after 4
      courses, but no recurrent foci were detected in the residual lung tissue, and all
      of the metastatic liver foci had resolved. To date 6 courses have been completed,
      and no relapses have been detected by thoracic CT. We report a case in which it
      was possible to predict efficacy as a result of treatment based on anticancer
      drug sensitivity testing and measurements of nucleic acid metabolizing enzymes.

PMID- 17220685
TI  - [Advanced ovarian cancer with Sister Mary Joseph's nodule--a case report].
AB  - A metastatic umbilical tumor,which we call Sister Mary Joseph's nodule (SMJN), is
      a sign of poor prognosis despite the primary site of malignant tumor. We describe
      here a patient with an advanced ovarian cancer and SMJN. A 51-year-old woman was
      referred to our department for evaluation of an umbilical tumor. As a result of
      systemic examination, the patient was diagnosed as stage IV ovarian cancer and
      rapidly underwent an optimal operation. Postoperatively, the chemotherapy for
      advanced ovarian tumors was begun (paclitaxel 180 mg/m(2) and carboplatin AUC 5,
      10 courses every 3 weeks). The patient is well without signs of tumor recurrence
      or metastasis 10 months after the operation. Forty percent of all navel neoplasms
      are malignant tumors. It is important to perform a pathological examination of a
      navel neoplasm or a systemic examination as fast as possible.

PMID- 17220686
TI  - [Four cases of therapy-related leukemia in multiple myeloma].
AB  - We have experienced 4 cases of therapy-related leukemia (TRL) in 119 patients
      with multiple myeloma (MM) who had received combination chemotherapy including
      alkylating agents between 1988 and 1998. All 4 cases were acute myelogenous
      leukemia, 3 were males and 1 was female. Median age at diagnosis of MM was 60
      years, and median time to TRL from diagnosis of MM was 5.5 years. The chromosome
      abnormalities were found in 3 of those cases. All 4 cases were resistant to
      antileukemic chemotherapy, and median survival time from TRL was only 5.5 months.
      The TRL in MM is thought to be a more important problem, because recently the
      treatment for this disease has become more intensive, including high-dose
      chemotherapy supported by autologous stem cell transplantation.

PMID- 17220687
TI  - [Concurrent chemo-radiotherapy for localized refractory non-Hodgkin's lymphoma-
      report of two cases].
AB  - Localized refractory diffuse large B-cell lymphomas (DLBCL) were treated with
      concurrent chemo-radiotherapy. Case 1 had right cervical lymphadenopathy.
      Lymphoma enlarged even after the fourth courses of chemotherapy consisting of
      cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). The second
      case had a pharyngeal tumor and bilateral cervical lymphadenopathy. A lymphoma
      enlarged after eighth courses of CHOP. Both cases were treated with concurrent
      chemo-radiotherapy. Chemotherapy consisted of mitoxantrone, methotrexate,
      ifosfamide,and prednisolone (MMIP). The dose of radiation to the involved sites
      was 40 Gy. The first case received chemotherapy three days after radiotherapy was
      started. The second case was treated with chemotherapy, and radiotherapy was
      begun one day after. Both cases show mucositis and leukopenia. One case received
      two courses of chemotherapy after chemo-radiotherapy, and the other received no
      additional chemotherapy. Both cases achieved complete remission after the
      combined therapy, however, lymphoma in one case recurred three months after the
      therapy. It is possible that this concurrent chemo-radiotherapy is effective for
      localized DLBCL which did not disappear after standard chemotherapy.

PMID- 17220688
TI  - Animal and human tissue Na,K-ATPase in obesity and diabetes: A new proposed
      enzyme regulation.
AB  - BACKGROUND: Na,K-ATPase is a membrane enzyme that energizes the Na-pump,
      hydrolyzing ATP and wasting energy as heat. It may play a role in thermogenesis,
      energy balance, and obesity development. Regulation of the enzyme by insulin is
      controversial. METHODS: In animal and human obesity, tissue Na,K-ATPase was
      assayed by colorimetric measurement of released Pi. RESULTS: Na,K-ATPase of
      hyperglycemic-hyperinsulinemic ob/ob mice (compared with lean control animals)
      was reduced in liver (-63%) and in kidney (-47%) (P < 0.001 in both instances).
      In contrast, in streptozotocin-treated hypoinsulinemic-diabetic Swiss mice,
      versus untreated animals, we found an increase of liver (+54%, P < 0.01) and
      kidney (+94%, P < 0.001) Na,K-ATPase. The enzyme was also increased (+99%, P <
      0.05) in kidney from ob/ob mice made diabetic-hypoinsulinemic with streptozotocin
      (versus untreated obese animals). This is contrary to the occurrence of a genetic
      enzymatic defect and suggests regulation by hyperinsulinemia, present in ob/ob
      mice. A positive correlation between tissue enzyme activity and glycemia existed
      in both ob/ob and Swiss mice. In adipose tissue from obese patients (compared
      with lean subjects), Na,K-ATPase was reduced (-65%, P < 0.001) and negatively
      correlated with body mass index, oral glucose tolerance test-insulinemic area,
      and mean blood pressure. In vitro, in human liver tissue, 3 mug/mL glucagon
      exerted a statistically inhibitory effect on Na,K-ATPase (-44%). CONCLUSION: We
      hypothesize that animal and human obesity is associated with reduction of tissue
      Na,K-ATPase, linked to hyperinsulinemia, which may repress or inactivate the
      enzyme, influencing thermogenesis and energy balance.

PMID- 17220689
TI  - The Pro12Ala polymorphism in PPARgamma2 gene affects lipid parameters in Greek
      primary school children: A case of gene-to-gender interaction.
AB  - BACKGROUND: In the present study we sought to evaluate the impact of the PPAR
      gamma2 Pro12Ala polymorphism on blood lipid levels of primary school children.
      METHODS: 81 male and 92 female schoolchildren were genotyped. Biochemical,
      anthropometric, and lifestyle variables were assessed. RESULTS: 14.1% females and
      14.8% males were heterozygotes, while the rest of the subjects were homozygotes
      for the Pro allele. A significant interaction between the PPARgamma-2 gene and
      gender on blood lipid levels was detected. In particular, Pro/Pro females
      exhibited higher values of total cholesterol (194 +/- 32 vs 180 +/- 28 mg/dL, P =
      0.06) and triglycerides (94 +/- 31 vs 77 +/- 11 mg/dL, P = 0.045) compared to
      Pro/Ala individuals. The gene-to-gender interaction term was highly significant
      (P < 0.001). On the other hand, Pro/Pro males showed higher values of HDL
      cholesterol (47 +/- 8 vs 43 +/- 9 mg/dL, P = 0.001), lower total cholesterol/HDL
      ratio (4.04 +/- 0.59 vs 4.45 +/- 0.61, P = 0.031), lower values of apoB (59.8 +/-
      11.3 vs 66.8 +/- 6.6 mg/dL, P = 0.007) and lower values of apoB/apoA1 ratio (0.41
      +/- 0.09 vs 0.48 +/- 0.08, P = 0.019) compared with Pro/Ala. Even after adjusting
      for body mass index (BMI), total energy intake, total fat intake and saturated
      fat intake, differences in total cholesterol/high-density lipoprotein (HDL)
      cholesterol and the apoB/apoA1 ratios remained significant. Regarding females, no
      differences were observed among genotypes concerning total cholesterol/HDL levels
      (P for gene-to-gender interaction = 0.001) and the apoB/apoA1 levels (P for gene
      to-gender interaction = 0.029). CONCLUSION: We show for the first time a gene-to
      gender interaction on total cholesterol/HDL and apoB/apoA1 ratios, in male
      schoolchildren genotyped for PPAR-gamma2 Pro12Ala.

PMID- 17220690
TI  - Proteomics on the diagnostic horizon: Lessons from rheumatology.
AB  - Rheumatology abounds in diseases that are relatively poorly understood or
      diseases that are not easily managed clinically. Recently DNA microarray and
      proteomic-based approaches have made steady inroads into the study of various
      rheumatic diseases. Herein we review recent proteomic approaches that have been
      applied to the study of rheumatic diseases. These methods include two-dimensional
      gel electrophoresis/mass spectrometry (MS), multidimensional high-pressure liquid
      chromatography-MS/MS, capillary electrophoresis-MS/MS, surface-enhanced laser
      desorption/ionization-time of flight-MS/MS, and a variety of targeted antibody
      based protein arrays. Although each of these different methods has its own
      advantages and disadvantages, the application of these proteomic tools to
      rheumatology has given birth to a steadily increasing panel of molecules that may
      have the potential to serve as early biomarkers in various rheumatic diseases.

PMID- 17220691
TI  - The cost-effectiveness of two strategies for vaccinating US veterans with
      hepatitis C virus infection against hepatitis A and hepatitis B viruses.
AB  - OBJECTIVES: Although hepatitis A and B vaccinations are recommended for patients
      with chronic hepatitis C virus (HCV), the ideal vaccination strategy has not been
      determined. Our objective was to model the cost-effectiveness of two strategies
      for vaccinating patients with HCV infection against hepatitis A (HAV) and
      hepatitis B (HBV) viruses. The strategies evaluated were: universal vaccination
      with the combined HAV and HBV vaccine, and selective vaccination based on
      immunity determined by blood testing. METHODS: A decision tree model was
      constructed to compare the cost-effectiveness of the two vaccination strategies
      from the New Mexico Veterans Affairs Health Care System (NMVAHCS) perspective. A
      retrospective review of all HCV patients (2517 subjects) at the NMVAHCS was
      performed to extract prevalence of immunity to HAV and HBV, and prevalence of
      decompensated liver disease. Literature review was performed to obtain other
      probabilities for the model. Only direct medical costs were considered; the
      effectiveness measure was the number of patients immune to both HAV and HBV.
      Sensitivity analyses were performed to test robustness of the results to changes
      in input variables. All costs were in 2004 US dollars. RESULTS: The selective
      strategy was less costly but less effective, with a cost-effectiveness ratio of
      105 dollars per patient immune to HAV and HBV. The universal strategy was more
      effective but more expensive with a cost-effectiveness ratio of 112 dollars per
      patient immune to HAV and HBV. Compared with the selective strategy, universal
      strategy was associated with an incremental cost-effectiveness (ICE) ratio of 154
      dollars per additional patient immune to HAV and HBV. The universal strategy
      would become more cost-effective if 1) the cost of combined vaccine was reduced
      to less than 30.75 dollars (9.7% reduction), 2) the cost of HBV vaccine increased
      to greater than 34.50 dollars (25% increase), 3) the cost of blood tests for
      immunity increased to more than 25.25 dollars (23% increase), or (4) the
      prevalence of anti-HBs decreased to less than 24%. CONCLUSIONS: The selective
      vaccination strategy for HAV and HBV in our sample of patients with HCV is more
      cost-effective. However, the universal strategy is more effective and its ICE is
      minimal, thus it may be worth the additional cost.

PMID- 17220692
TI  - Management of diabetes in older adults.
AB  - Enhanced life expectancy and the aging of society have conspired with rising
      rates of obesity and physical inactivity to cause an unprecedented increase in
      diabetes prevalence worldwide. The disease and its chronic complications have
      unique presentations and challenges in the elderly. Postprandial hyperglycemia
      may be the predominant manifestation, comorbid health conditions are often
      present, and the risk of cardiovascular disease is vastly increased. Periodic
      screening is essential for early diagnosis and proper treatment. The principles
      of multidisciplinary management emphasizing nutrition, exercise, education,
      psychosocial care, attention to concomitant metabolic risk factors, and prudent
      use of pharmacologic agents are the mainstay of therapy for older adults.
      Treatment should be tailored to the individual patient, and the assistance of
      family and caregivers should be combined with rational utilization of community
      resources. An evidence-based, comprehensive, and proactive approach is needed to
      reduce the burden of morbidity and mortality from diabetes in the elderly.

PMID- 17220693
TI  - Symptomatic ascites in a patient with hypothyroidism of short duration.
AB  - Symptomatic ascites as a presenting symptom of hypothyroidism is quite rare. In
      most of the case reports, patients with ascites requiring therapeutic abdominal
      paracentesis have long-standing hypothyroidism. We present a case of symptomatic
      ascites in a subject with hypothyroidism following radioiodine therapy for Graves
      disease. A 70-year-old African-American man presented with increasing weakness,
      shortness of breath, weight gain, constipation, and abdominal distention. Past
      history was significant for coronary artery disease, diabetes, hypertension and
      history of radioiodine therapy for Graves disease 9 months prior to the
      presentation. He was taking levothyroxine at 50 microg per day for 3 months prior
      to the presentation. Physical examination findings were significant for puffiness
      around the eyes, decreased breath sounds at the lung bases, and distended abdomen
      with free fluid, hung-up reflexes, and cold extremities. The thyroid-stimulating
      hormone level at the time was 64 with a free T4 less than 0.4 ng/dL. Analysis of
      the ascitic fluid revealed an exudative effusion with a serum to ascitic fluid
      albumin gradient of 1.2. The patient required therapeutic abdominal paracentesis
      twice, with 4 L each time, to relieve the symptoms. Work-up to rule out other
      causes did not reveal any other relevant abnormality. After initiation of thyroid
      hormone replacement, the patient responded very well and the ascites resolved
      within 2 months. We conclude that ascites associated with hypothyroidism is rare
      but must be recognized early, since thyroid replacement is the definitive
      therapy.

PMID- 17220694
TI  - Refractive hypotension in a patient with disulfiram-ethanol reaction.
AB  - Disulfiram (Antabuse) is used for aversive treatment of alcohol dependence with
      good effects. Through inhibition of aldehyde dehydrogenase, disulfiram heightens
      serum aldehyde concentration after alcohol ingestion and causes aversive
      disulfiram-ethanol reaction. Typical symptoms of this reaction include flushing,
      nausea, dyspnea, tremor, and confusion, which are usually self-limiting. However,
      severe life-threatening arterial hypotension sometimes develops. We report here a
      patient with generalized flushing, tremor, and refractive hypotension after
      ingestion of alcohol 18 hours after disulfiram treatment. Initial volume
      resuscitation and dopamine infusion failed to restore the blood pressure.
      Noradrenaline was given and the blood pressure returned to normal range. This
      case illustrates the intensity of disulfiram-ethanol reaction and underscores the
      advantageous use of noradrenaline in patients in such a critical condition.

PMID- 17220695
TI  - Herpes zoster ophthalmicus and syndrome of inappropriate antidiuretic hormone
      secretion.
AB  - Presented here is a case of syndrome of inappropriate antidiuretic hormone
      secretion (SIADH) that developed in an elderly woman with single dermatomal
      herpes varicella zoster ophthalmicus without evidence of varicella-zoster
      encephalitis or dissemination. This is only the third such case reported in the
      English language literature to date, and it affirms that SIADH can develop in
      patients with herpetic involvement of just a single dermatome and corrects with
      resolution of the herpetic lesions.

PMID- 17220696
TI  - Osteomalacia and secondary hyperparathyroidism after kidney transplantation:
      Relationship to vitamin D deficiency.
AB  - Secondary hyperparathyroidism is highly prevalent in patients with end-stage
      renal disease. After successful kidney transplantation, however, parathyroid
      glands gradually involute to normal size with subsequent normalization of intact
      parathyroid hormone (PTH), serum calcium, and phosphorous concentrations. This
      report describes a 48-year-old diabetic end-stage renal disease patient who
      underwent a successful cadaveric kidney transplant. Serum calcium and phosphorous
      concentrations normalized within 6 months. Three years later, he presented with
      complaints of proximal muscle weakness that was progressively worsening. Physical
      examination revealed temporal wasting and proximal muscle weakness. Detailed
      neurologic examination was unremarkable except for decreased vibratory sensation
      in both feet. Laboratory data showed stable allograft function (serum creatinine,
      1.3 mg/dL), hypocalcemia, and hypophosphatemia with markedly elevated alkaline
      phosphatase level (726 IU/L) and intact PTH level (947 pg/mL). Further laboratory
      evaluation revealed poor nutritional status and severe deficiency of 25(OH)D (4.0
      ng/mL). Past medical history included remote episodes of acute pancreatitis due
      to prior alcohol abuse. Computed tomography of the abdomen showed calcific
      atrophic pancreas, and steatorrhea was confirmed on stool studies. Decreased bone
      mineral density was noted by computed tomography bone density scan. Secondary
      hyperparathyroidism and osteomalacia had developed due to severe vitamin D
      deficiency, occurring as a result of previously unrecognized, minimally
      symptomatic pancreatic exocrine insufficiency. Treatment with vitamin D, calcium,
      and pancreatic enzyme replacement led to remarkable resolution of clinical
      symptoms and secondary hyperparathyroidism (intact PTH, 65 pg/mL after therapy)
      and resulted in significant improvement in bone mineralization. Factors
      associated with vitamin D deficiency in the chronic kidney disease and post
      transplant patient population are reviewed.

PMID- 17220697
TI  - A rare case of clear cell adenocarcinoma of the bladder with unique pathological
      features.
AB  - Clear cell adenocarcinomas of the urinary bladder are rare tumors with an unknown
      histogenesis. Since these tumors appear histologically similar to clear cell
      tumors of the female genital tract, a mullerian histogenesis has been proposed.
      Several publications have examined the immunohistochemical properties of clear
      cell adenocarcinomas to improve understanding of the cause and pathogenesis of
      this tumor. While specific criteria for a diagnosis of clear cell adenocarcinoma
      have not been defined, there are consistent staining patterns suggested for
      characterization. We present an important case of clear cell adenocarcinoma of
      the bladder with a unique staining pattern. We review the literature and discuss
      the differential diagnosis and various theories concerning the origin of this
      rare tumor.

PMID- 17220698
TI  - Changing sites of colorectal cancer in the Israeli Jewish ethnic populations and
      its clinical implications.
AB  - Countries at risk for colorectal cancer noted an increase in right-sided
      colorectal cancer. We examined this in the Israeli Jewish populations. Israel
      Cancer Registry data, 1982-2001, were computed by sex, age, ethnic group and
      colorectal cancer site: 'rectal cancer' included the recto-sigmoid junction,
      'right-sided' colorectal cancer included proximal colon up to and including the
      splenic flexure. In both sexes, colorectal cancer trends increased significantly
      owing to colonic cancer (P<0.01) whereas rectal cancer decreased (P<0.01). Left
      and right colorectal cancer trends decreased in Israel born people (P<0.01), but
      in Asia-Africa born people increases were seen at both sites in the male (P=0.02
      and 0.06, respectively) and female (P=0.03 and 0.01, respectively) population. In
      those > or =65 years old, right colorectal cancer trends increased in all men
      (P=0.05) and women (P=0.01). On comparing data from 1982-1986 with that from 1997
      2001 right colorectal cancer showed an increase in both sexes (P<0.01): to 32.7%
      of male colorectal cancer and 57.6% of female colorectal cancer. In the period
      1997-2001, the total male population > or =65 years had increased relatively by
      7.5% (P<0.01), and women by 22.6% (P<0.01) and the proportion of right colorectal
      cancer in > or =65 years olds increased relatively by 10.9% in the male
      population, and 18.2% in the female population, with one-third of this increase
      occurring in Russian immigrants arriving after 1990. In conclusion, there is a
      trend for right colorectal cancer in Jews aged > or =65 years. The proportion and
      amount of colorectal cancer increased most significantly in older women, which
      was partially explained by their increasing numbers and by colorectal cancer
      occurring in recent immigrants from Russia, who were at high-risk for colorectal
      cancer. These results should influence colorectal cancer screening and diagnostic
      methodologies used.

PMID- 17220699
TI  - Colorectal cancer incidence, mortality and survival in South-east England between
      1972 and 2001.
AB  - We report incidence, mortality and survival from colorectal cancer in South-east
      England using data from 162,022 incident cases and 97,697 deaths collected
      between 1972 and 2001 at the Thames Cancer Registry, which currently covers 14
      million people. Overall, there was an increase in the incidence of colorectal
      cancer among men aged 50 years and over, and a decrease among the youngest age
      groups. In women, there was a clear decrease in incidence among those aged less
      than 60 years but a slight increase among those aged 60-79 years. Furthermore,
      there has been a steady decrease in mortality for all ages, larger in women than
      in men, and an increase in the 10-year relative survival for both sexes from just
      over 30% among those followed-up during 1981-1986 to just over 45% among those
      followed-up during 1997-2001.

PMID- 17220700
TI  - Effects of lifestyle on the onset of puberty as determinant for breast cancer.
AB  - Breast cancer is more than ever the leading cause of death in women. In this
      article, we investigate the influence of lifestyle factors, and in particular
      nutrition (i.e. soft drinks), on physical development, puberty, breast growth and
      menarche to understand the potential impact of these environmental and lifestyle
      factors on the induction of breast cancer susceptibility. A questionnaire was
      obtained from 1146 girls of 10 schools in Belgian Limburg, attending the second
      year of secondary school. Their mean age was about 13 years. The analyses of the
      data were performed with 'survival analysis', in particular with the 'Cox
      regression' model for menarche. This project was conducted in the school year of
      1999-2000. In the univariate and multivariate analysis investigating the most
      important variables of the period from birth to the age of menarche, there was
      clear evidence that lifestyle factors, including nutrition, have an effect on
      breast development and menarche. The following variables were significantly
      related to breast development and menarche: body mass index, drinking high
      carbohydrate drinks, i.e. soft drinks, height of the father and the mother,
      weight of the mother at the start of pregnancy, history of mononucleosis, origin
      and education of the parents and physical activity. Lifestyle factors, including
      nutrition (i.e. soft drinks), affect the age at puberty and menarche. The same
      factors are known to be related to breast cancer risk. Better control of these
      variables during puberty might reduce breast cancer risk later in life.

PMID- 17220701
TI  - Evaluation of a combined screening programme for breast, cervical and colorectal
      cancers in France.
AB  - A combined breast, cervical and colorectal cancer screening programme was set up
      in 1990 in Isere, for women aged 50-69 years (target population 100,000)
      comprising an initial medical visit. The programme was evaluated in 1997. The
      evaluation covered uptake results, sensitivity, specificity, two opinion surveys
      among 1025 physicians and 400 women to measure the impact, and three surveys
      regarding radiologists', gastroenterologists' and pathologists' attitudes.
      Sensitivity and specificity rates were 74 and 87% for breast, 83 and 99% for
      cervical and 43 and 97% for colorectal screening. The number of cervical smears
      completed by women aged 60-69 years doubled with the programme. Acceptability of
      the faecal occult blood test was 88%. Eighty percent of physicians were in favour
      of the programme but 67% said that they often prescribed outside the programme.
      Overall, 71% of the interviewed women said they had had a breast screen, 69% a
      Pap smear and 53% a faecal occult blood test when only 25-35% of the target
      population was actually recorded in the programme. This programme increased the
      uptake of women not previously screened both within and outside the programme. It
      showed discrepancies between beliefs and practices of physicians. Protocol
      changes were implemented after this evaluation.

PMID- 17220702
TI  - A comparison of trends in incidence and mortality rates of breast cancer,
      incidence to mortality ratio and stage at diagnosis between Arab and Jewish women
      in Israel, 1979-2002.
AB  - In Israel, breast cancer is the most common malignancy in women, but there are
      large intra-population differences. The aim of this study was to compare the
      incidence and mortality, incidence to mortality rate ratio and stage at diagnosis
      of breast cancer between Arab and Jewish women in Israel. Data on all cases of
      breast cancer, stage at diagnosis and mortality were obtained from the National
      Cancer Registry and the Central Bureau of Statistics. Trends in age-specific and
      age-adjusted incidence and mortality rates, rate ratios and stage at diagnosis
      were examined for Arab and Jewish women during 1979-2002. Five-year survival
      rates for 1995-1999 were compared by stage. Among Arab women, age-adjusted
      incidence rates increased by 202.1%, from 14.1 per 100,000 in 1979-1981 to 42.6
      in 2000-2002. Among Jewish women, the rates increased by 45.7%, from 71.1 per
      100,000 women in 1979-1981 to 103.6 in 2000-2002. Incidence to mortality rate
      ratio increased for both population groups, but it is still lower among Arab
      women. In every age group, Arab women were more likely to be diagnosed at a more
      advanced stage of the disease. The rise in breast cancer incidence and mortality
      rates and the later stage of diagnosis among Arab women emphasize the urgent need
      for increasing early detection of breast cancer in the Arab population by
      improving rates of compliance with screening mammography.

PMID- 17220703
TI  - Family history of breast cancer and compliance with mammography in Israel:
      findings of the National Health Survey 2003-2004 (EUROHIS).
AB  - A positive family history of breast cancer is an established risk factor for the
      disease. In Israel, screening is recommended annually for high-risk women aged >
      or =40 years and biennially for average-risk women aged > or =50 years. The
      current study aimed to assess the effect of having a positive breast cancer
      family history on performing screening mammography in Israeli women. This study
      is a cross-sectional survey based on a random sample of the Israeli population,
      conducted in 2003. The study was carried out by means of telephone interviews
      that included questions on the use of preventive medical services. The current
      study population consists of 1605 Israeli women aged 40-74 years. A positive
      family history for breast cancer was reported by 153 (9.5%) of the participants.
      A mammogram in the previous year was reported by 43.1 and 24.7% of the positive
      and negative family history subgroups, respectively (P<0.0001). Rates increased
      with age. Among women with a positive family history, only being married was a
      significant correlate for a mammography in the previous year. Over 60% and around
      55% of high-risk women aged 40-49 and > or =50 years, respectively, are
      inadequately screened for breast cancer. Screening rates are not optimal in the
      average-risk group as well.

PMID- 17220704
TI  - Melanoma incidence in central Italy will go on increasing also in the near
      future: a registry-based, age-period-cohort analysis.
AB  - The aim of the study was to evaluate malignant melanoma incident trends in
      central Italy by means of an age-period-cohort approach. A total of 1977
      malignant melanoma (15-84 years) incidents in the area of the Tuscany Cancer
      Registry between 1987 and 2001 were analysed. Poisson regression has been used to
      estimate age, cohort and period effect. A nonlinear regression model was used to
      estimate the expected number of new cases in the period 2002-2006. Incidence
      rates increased in all age, period and cohort groups. The model that best fitted
      the data included age and 'drift'. The linear effect ('drift') showed, in each
      age group, an increase of the risk of malignant melanoma diagnosis of about 36.6%
      every 5 years of period or cohort. For the period 2002-2006, 1112 new cases were
      predicted with a standardized rate (age 15-84 years) of 19.2x100.000. In the
      Tuscany Cancer Registry area, no clues for malignant melanoma incidence rates
      levelling off were documented. Growing rates and number of malignant melanoma are
      expected in the near future.

PMID- 17220705
TI  - Hypothesis of the cause and development of neoplasms.
AB  - Cancer, in general, is considered a disease of genetic mutation. Many questions
      are, however, unanswered. How exactly do mutations occur in the cells? How do
      gene mutations interface with the cell microenvironment and macroenvironment to
      create cancer phenotypes? Is mutation the cause of cancer or the consequence of
      special adaptive responses to aging; hormonal imbalance; physical, chemical and
      biologic stresses and damage? What makes cancer spread in the body and invade
      other organs causing death to the patient? In this paper, we hypothesize that the
      cellular hyperexcitability via stimulation of mineral channels (e.g. sodium
      voltage-gated channels) and ligand excitatory receptors (e.g. glutamate and other
      neuron and non-neuronal excitatory receptors) could be a significant causative
      and pathogenic factor of cancer. Managing hyperexcitatory states of the cells
      through lifestyle, nutritional changes, phytochemical and pharmaceutical
      medications theoretically could be a prospective direction in cancer prevention
      and therapy.

PMID- 17220706
TI  - Time trends and geographic variations for thyroid cancer in New Caledonia, a very
      high incidence area (1985-1999).
AB  - Thyroid cancer incidence in New Caledonia is the highest reported in the world
      and is approximately 10-fold higher than in most developed countries. We describe
      the incidence patterns in this country according to histological and
      sociodemographic characteristics to give clues about potential etiologic factors.
      Another objective is to see whether the incidence figures are related to enhanced
      detection of small size carcinomas. The study included all 498 cases of thyroid
      cancer diagnosed in 1985-1999. Pathology reports were systematically reviewed to
      determine the histological type of the tumor and the size of the cancerous
      nodules. The incidence of carcinomas < or =10 mm was taken as an indicator of
      enhanced detection due to improved screening procedures. The age-standardized
      incidence rates in 1985-1999 were exceptionally high in Melanesian women
      (71.4/100,000) and men (10.4/100,000). The incidence increased three-fold in
      women from 1995 onwards. The increase in incidence was more striking for
      papillary carcinomas < or =10 mm than for large size carcinomas, but an increased
      incidence of carcinomas >10 mm was also observed among women. The analysis by
      municipality of residence in Melanesian women showed that the incidence was twice
      as high in 1995-1999 in the Loyalty Islands as in the rest of the country. The
      sharp increase of thyroid cancer incidence in 1985-1999 in New Caledonia was
      partly related to enhanced detection of small size carcinomas. The elevated
      incidence of thyroid cancers, as well as the ethnic and geographic disparities,
      may result from common environmental or lifestyle risk factors that need to be
      identified.

PMID- 17220707
TI  - Adverse health indicators correlating with sparsely populated areas in Sweden.
AB  - Earlier studies on health characteristics in Sweden have pointed at a sudden
      trend change in general health indicators around 1997. The decline was worse in
      areas with less estimated coverage by the mobile phone system; that is, areas
      where the average output power from mobile phone handsets is expected to be
      higher. In this study, health parameters were related to the population density,
      which is a well defined, rather than an estimated variable. Statistics were
      obtained from different authorities in Sweden. Data were correlated to the
      population densities in the 21 different counties of Sweden as well as to
      estimates of average mobile phone output power. Several health quality measures
      showed that people in sparsely populated counties in Sweden (as well as in
      Denmark and Norway) have suffered more illness, and lengthier recovery than
      people in more densely populated areas since 1997. This is in strong contrast to
      the situation 20 years ago, when the countryside was the healthiest place in
      which to live. The indicators strongly correlated with estimated mobile phone
      area coverage and estimated power output. The indicator statistics suggest that
      the decline in health in Sweden is not a primary consequence of low population
      density by itself, but that other factors related to population density are
      causative. The two factors having the strongest correlation with decreased health
      quality were the estimated average power output from mobile phones (positive
      correlation) and the reported coverage from the global system for mobile
      communication base stations (negative correlation) in each county.

PMID- 17220708
TI  - Cellular telephone use and time trends in brain tumour mortality in Switzerland
      from 1969 to 2002.
AB  - A rising concern exists that with the widespread use of mobile communication
      technologies, the incidence of brain tumours may increase. On the basis of data
      from the Swiss national mortality registry from 1969 to 2002, annual age
      standardized brain tumour mortality rates per 100,000 person-years were
      calculated using the European standard population. Time trend analyses were
      performed by the Poisson regression for six different age groups in men and women
      separately. The study period was divided into two intervals: before and after
      1987, when the analogue mobile technology was introduced in Switzerland. Age
      standardized brain tumour mortality rates ranged between 3.7 and 6.7 for men and
      2.5 and 4.4 for women per 100,000 person-years. For the whole study period, a
      significant increase in brain tumour mortality was observed for men and women in
      the older age groups (60-74 and 75+ years) but not in the younger ones in whom
      mobile phone use was more prevalent. Time trend analyses restricted to data from
      1987 onwards revealed relatively stable brain tumour mortality rates in all age
      groups. For instance, the annual change in brain tumour mortality rate for the 45
      59-year age group was -0.3% (95% confidence interval: -1.7; 1.1) for men and 
      0.4% (95% confidence interval:-2.2; 1.3) for women. We conclude that after the
      introduction of mobile phone technology in Switzerland, brain tumour mortality
      rates remained stable in all age groups. Our results suggest that mobile phone
      use is not a strong risk factor in the short term for mortality from brain
      tumours. Ecological analyses like this, however, are limited in their ability to
      reveal potentially small increases in risk for diseases with a long latency
      period.

PMID- 17220709
TI  - Diabetes and cancer risk for all and specific sites among Japanese men and women.
AB  - Associations between diabetes and multisite cancer risk were examined in a case
      control study of 11,672 incident cancer cases (5341 men and 6331 women) and
      47,768 cancer-free controls (14,199 men and 33,569 women). Using an unconditional
      logistic regression model and controlling for potential confounding factors, a
      past/present history of diabetes was associated with cancer risks for all sites
      in both men and women (odds ratios=1.44 and 1.39, 95% confidence intervals=1.28
      1.62 and 1.19-1.62), respectively. Significantly increased risk was found for
      cancers of the pharynx, esophagus, colorectum, liver, pancreas, larynx and lung
      among men, and of the stomach, liver, lung and cervix uteri among women. Among
      participants with a family history of diabetes, a past/present history of
      diabetes was also associated with cancer risks of all sites among men and women
      (odds ratios=1.41 and 1.96, 95% confidence intervals=1.04-1.93 and 1.44-2.68,
      respectively). The associations were highest for pancreatic cancer among men and
      the stomach, colorectum and corpus uteri among women. Our findings support the
      conclusion that diabetes is associated with the etiology of cancer development,
      and we suggest that a family history of diabetes should be considered as a risk
      factor for several cancer sites among participants with a past/present history of
      diabetes.

PMID- 17220710
TI  - Detection of tumour thrombus by 18F-FDG-PET/CT imaging.
AB  - Tumour thrombus is a rare complication of many solid cancers including renal cell
      carcinoma, Wilms' tumour, testicular tumour, adrenal cortical carcinoma,
      lymphoma, pancreatic cancer, osteosarcoma and Ewing's sarcoma. We describe six
      patients who harboured occult tumour thrombus detected by fluorine-18
      fluorodeoxyglucose (F-FDG) positron emission tomography (PET)/X-ray computerized
      tomography (CT) imaging as part of the staging investigations. Recognition of
      this rare complication by PET/CT can change the management plan and prevent
      unnecessary long-term anti-coagulation treatment because of wrong diagnosis of
      cancer-related venous thrombus.

PMID- 17220711
TI  - The Hanford Thyroid Disease Study: an alternative view of the findings.
AB  - The Hanford Thyroid Disease Study (HTDS) is one of the largest and most complex
      epidemiologic studies of the relation between environmental exposures to I and
      thyroid disease. The study detected no dose-response relation using a 0.05 level
      for statistical significance. The results for thyroid cancer appear inconsistent
      with those from other studies of populations with similar exposures, and either
      reflect inadequate statistical power, bias, or unique relations between exposure
      and disease risk. In this paper, we explore these possibilities, and present
      evidence that the HTDS statistical power was inadequate due to complex
      uncertainties associated with the mathematical models and assumptions used to
      reconstruct individual doses. We conclude that, at the very least, the confidence
      intervals reported by the HTDS for thyroid cancer and other thyroid diseases are
      too narrow because they fail to reflect key uncertainties in the measurement
      error structure. We recommend that the HTDS results be interpreted as
      inconclusive rather than as evidence for little or no disease risk from Hanford
      exposures.

PMID- 17220712
TI  - Extremity dosimetry for radiation workers handling unsealed radionuclides in
      nuclear medicine departments in India.
AB  - In India, for the past five decades, whole body radiation dose of radiation
      workers has been monitored by means of film and thermoluminescent dosimeter (TLD)
      badges worn on the body. However, there are no provision/regulatory requirements
      to monitor doses received at the extremities, i.e., to fingers. Finger dose
      monitoring is essential for controlling the extremity dose limits for
      occupational personnel handling unsealed radioactive sources. In order to
      estimate the doses received in various types of procedures using unsealed
      sources, finger dose monitoring was carried out in 54 major institutions in the
      country using a specially designed plastic finger ring embedded with a TLD. The
      maximum finger dose of occupational workers involved in handling Tc in such
      activities as extraction and radiopharmacy work is 0.35 mSv GBq; during injection
      of radiopharmaceuticals and scintigraphy, the doses were observed to be 1 and
      0.95 mSv GBq, respectively. Similarly, while handling F-FDG, the maximum doses
      received during dispensing, injection, and scintigraphy were 0.098, 0.324, and
      0.56 mSv GBq, respectively. The maximum radiation dose received during Re/Re
      balloon angioplasty and while handling Sm was 3.92 and 6.5 mSv GBq, respectively.
      All the doses recorded were well within the prescribed limit. However, monitoring
      of these doses periodically would help in compiling the feedback regarding the
      work practices followed in institutions handling radioisotopes in the country and
      would also help in maintaining a record of safe work procedures while handling
      radioisotopes.

PMID- 17220713
TI  - Age dependence of natural uranium and thorium concentrations in bone.
AB  - The age dependence of the natural concentration of uranium and thorium in the
      skeleton was investigated using human vertebrae bone collected from two Canadian
      locations (Winnipeg, Manitoba, and Regina, Saskatchewan). The concentration of
      both radioelements in digested ashed bone samples was determined using sector
      field inductively coupled plasma mass spectrometry. The geometric means for
      uranium level in bones showed a significant statistical difference between the
      two locations studied. Similarly for thorium, a statistical difference was
      observed, although this difference was considered marginal. The thorium
      concentration differed only marginally with respect to age group, indicating that
      its behavior in the body could be age-independent. Conversely, the uranium level
      in bones was found to change for the age groups tested, an indication of age
      specific deposition. The age profile for uranium was comparable to the calcium
      turn-over rate, indicating that uranium deposition is probably, in part, dictated
      by this metabolic process, showing the role of present uptake into the uranium
      concentration in bones for populations exposed to significant uranium intake.

PMID- 17220714
TI  - Factors affecting dose estimates for long-term performance assessments: case
      study-Armagosa Valley.
AB  - The purpose of this study was to review and evaluate some of the factors that
      influence the dose estimates to members of the public due to chronic, long-term
      releases of radioactive materials into the environment. Although the examples
      discussed are based on data from the Amargosa Valley located near the proposed
      Yucca Mountain high-level radioactive waste repository, the factors evaluated are
      common to any such assessment. While it is recognized that such factors include
      those related to both the environmental transport of radionuclides from the point
      of release through the environmental media to the receptor, and the influence of
      his/her location and living habits, the assessments that follow are primarily
      limited to the latter. The specific goal in all cases was to illustrate how the
      assumptions and input values relative to certain factors influence the dose
      estimates and to quantify, to the extent possible, their relative significance.
      At the same time, it must be recognized that the assessments presented here were
      limited to doses due to the ingestion of food and water; those due to the
      inhalation of airborne radionuclides and external exposures were not considered.
      The factor that proved most important from the standpoint of the overestimation
      of doses (i.e., conservatism) was the implementation of the regulatory
      requirements pertaining to the withdrawal of groundwater from the local aquifer.
      Another significant source of conservatism was the dose estimates provided by the
      U.S. Department of Energy, assuming that the Reasonably Maximally Exposed
      Individual (RMEI) resided at the U.S. EPA designated site, 18 km from the
      repository, vs. the Amargosa Valley, about 35 km away. Also important, for
      selected radionuclides, was the impact of their effective half-lives on the
      committed doses, as estimated, in comparison to those that would actually be
      received. Having lesser impacts were the status of a local aquaculture farm on
      the intake of C, and the intake of stable iodine on dose estimates for I. On the
      basis of these evaluations, one can reasonably conclude that the overall
      conservatism in the dose assessments, based on these sources that were
      identified, approaches an order of magnitude. The sole factor that led to an
      underestimation of the doses (i.e., non-conservatism) was the regulatory
      requirement that the concept of the RMEI, as defined by U.S. EPA, in contrast to
      that of the Critical Group (CG), as recommended by the International Commission
      on Radiological Protection, be applied in estimating the doses to potentially
      affected population groups. Rather than dwell on the differences in the impacts
      of the application of each of these two concepts, the next step should be to
      subject each concept to a systematic and rigorous analysis, the goal being to
      gain an understanding of the range of dose estimates that would be yielded, the
      underlying reasons for the differences that are observed, and the lessons to be
      learned in terms of improving the methodologies for estimating doses due to
      environmental radionuclide releases.

PMID- 17220715
TI  - Assessment of current exposure of the population living in the Techa River basin
      from radioactive releases of the Mayak facility.
AB  - Current doses arising from external and internal pathways have been estimated for
      the residents of two villages, Muslumovo and Brodokalmak, alongside the Techa
      River, which was contaminated by radioactive releases from the Mayak production
      facility. The dose estimates are based on numerous environmental measurements
      supplemented by further human whole body measurements and studies on occupational
      and dietary habits of Slavic and Turkish ethnic groups. Estimated doses arise
      mainly from use of the contaminated floodplains alongside the Techa River. The
      current average annual effective dose attributable to Cs and Sr in the
      environment, under conditions where restrictions on some river-related activities
      are in place, may exceed the Russian national action level of 1 mSv only in the
      hypothetical critical group of herdsmen in Muslumovo. The dose to this critical
      group in Brodokalmak is assessed to be 3 times less than that in Muslumovo and 2
      fold below the action level. The external and internal exposures give comparable
      contributions to the total dose in both settlements and population groups: 47%
      and 53% in Muslumovo and 40% and 60% in Brodokalmak, respectively. About one
      quarter to one half of the internal dose in adults arises from the intake of Sr.
      In order to avoid substantial increases in the dose received by Muslumovo
      residents, it is expedient to prolong the current policy of restriction of some
      river-related population activities in this village.

PMID- 17220716
TI  - An experimental analysis of some of the factors affecting gross alpha-particle
      activity with an emphasis on 226Ra and its progeny.
AB  - This work presents an experimental investigation of the measurement of the gross
      alpha-particle activity of water samples by EPA Method 900.0. The residue
      produced in Method 900.0 is modeled by a BaSO4 precipitate distributed over a
      planchet. The dependence of the gross alpha-particle activity on the activity of
      Ra and its progeny, on the residue mass and geometry, and on the time between
      sample preparation and analysis is studied. It is shown that these factors can
      cause the gross alpha-particle activity of a sample to vary by more than a factor
      of three for replicate samples and to significantly overestimate the alpha
      activity of the residue. For a given sample geometry, the gross-alpha particle
      activity generally increases as the residue mass increases owing to the presence
      of the radium progeny.

PMID- 17220717
TI  - Radon and lung cancer risk: an extension of the mortality follow-up of the
      Newfoundland fluorspar cohort.
AB  - Radon is a well-recognized cause of lung cancer, and studies of underground
      miners have provided invaluable insights on the mechanisms of radon
      carcinogenesis. Given the dramatic decreases in occupational exposures and the
      latent interval between the time of exposure and the development of lung cancer,
      continued follow-up of these cohorts is needed to address uncertainties in risk
      estimates. Here, we report on the relationship between radon and lung cancer
      mortality in a cohort of 1,742 Newfoundland fluorspar miners between 1950 and
      2001; follow-up has been extended 11 y from previous analyses. The standardized
      mortality ratio (SMR) was used to compare the mortality experience of the cohort
      to similarly aged Newfoundland males. Poisson regression methods were used to
      characterize the radon-lung cancer relationship with respect to: age at first
      exposure, attained age, time since last exposure, interactions with cigarette
      smoking, and exposure rate. In total, 191 lung cancers were observed among
      underground miners (SMR = 3.09; 95% CI = 2.66, 3.56). ERR/WLMs decreased with
      attained age and time since last exposure. An inverse dose-rate effect was
      observed, while age at first exposure was not associated with lung cancer risk.
      An important strength of this study is that the effects of gamma radiation,
      thoron, and radioactive dust, common exposures in other miner studies, can be
      ruled out because the source of radon was from water running through the mine.
      However, the results should be interpreted cautiously due to uncertainties
      associated with the estimation of radon exposure levels before ventilation was
      introduced into the mine, and the relatively small number of lung cancer deaths
      that precluded joint modeling of multiple risk factors.

PMID- 17220718
TI  - The standfast whole body counter and the sliced BOMAB phantom: efficiency as a
      function of number of sources and energy modeled by MCNP5.
AB  - Previously, using Monte Carlo simulations, this laboratory conceptualized a new
      phantom: the sliced Bottle Manikin Absorber (BOMAB) phantom. It was intended for
      calibration or performance testing of whole body counters and the HML
      subsequently built and tested that phantom. Also, this laboratory tested another
      phantom used for the calibration of the StandFast whole body counter and
      identified some deficiencies. This paper investigates the use of the sliced BOMAB
      phantom as an alternative for the calibration of the StandFast and shows how the
      165 sources required for a full loading of the sliced BOMAB can be reduced to a
      much smaller number without compromising the calibration. The agreement of the
      sliced BOMAB with eight sources is approximately 1% when compared with a
      conventional BOMAB phantom.

PMID- 17220719
TI  - An absorbed dose map of bone tissue treated with a radiopharmaceutical in vivo.
AB  - A beagle humerus treated with Ho-chelate radiopharmaceutical in vivo was examined
      by electron paramagnetic resonance (EPR) dosimetry. The bone was sectioned and
      the absorbed dose to each bone fragment was determined by additive re-irradiation
      of the bone tissue with calibrated doses of gamma radiation. The measured doses
      ranged from 4.3 Gy to 62 Gy. The highest doses were recorded in the predominately
      trabecular bone tissue and the lowest doses in the predominately cortical bone
      tissue. The mean absorbed dose for the entire bone was 17 Gy. The data from 50
      bone fragments were combined to create an absorbed dose map of the interior bone
      surface.

PMID- 17220720
TI  - Photon extremity absorbed dose and kerma conversion coefficients for calibration
      geometries.
AB  - Absorbed dose and dose equivalent conversion coefficients are routinely used in
      personnel dosimetry programs. These conversion coefficients can be applied to
      particle fluences or to measured air kerma values to determine appropriate
      operational monitoring quantities such as the ambient dose equivalent or personal
      dose equivalent for a specific geometry. For personnel directly handling
      materials, the absorbed dose to the extremities is of concern. This work presents
      photon conversion coefficients for two extremity calibration geometries using
      finger and wrist/arm phantoms described in HPS N13.32. These conversion
      coefficients have been calculated as a function of photon energy in terms of the
      kerma and the absorbed dose using Monte Carlo techniques and the calibration
      geometries specified in HPS N13.32. Additionally, kerma and absorbed dose
      conversion coefficients for commonly used x-ray spectra and calibration source
      fields are presented. The kerma values calculated in this work for the x-ray
      spectra and calibration sources compare well to those listed in HPS N13.32. The
      absorbed dose values, however, differ significantly for higher energy photons
      because charged particle equilibrium conditions have not been satisfied for the
      shallow depth. Thus, the air-kerma-to-dose and exposure-to-dose conversion
      coefficients for Cs and Co listed in HPS N13.32 overestimate the absorbed dose to
      the extremities. Applying the conversion coefficients listed in HPS N13.32 for
      Cs, for example, would result in an overestimate of absorbed dose of 62% for the
      finger phantom and 55% for the wrist phantom.

PMID- 17220725
TI  - Coronary artery stenosis quantification using multislice computed tomography.
AB  - RATIONALE AND OBJECTIVES: Reliable noninvasive detection of stenoses with
      multislice computed tomography (MSCT) is feasible. This study's aim was to
      analyze the agreement, correlation, and reliability of MSCT with conventional
      coronary angiography as the reference standard for quantification of coronary
      artery stenoses. MATERIALS AND METHODS: A total of 118 significant (at least 50%)
      coronary artery stenoses with a reference vessel diameter of at least 1.5 mm in
      62 patients were analyzed by MSCT using 16 detector rows (Aquilion, Toshiba,
      Otawara, Japan), multisegment reconstruction, and voxel sizes of 0.35x0.35x0.5
      mm. The degree of stenosis on MSCT and quantitative coronary angiography (QCA)
      was measured by correlating the difference between the reference vessel diameter
      (average of 2 measurements directly proximal and distal to the stenosis) and the
      stenotic vessel diameter to the reference vessel diameter. RESULTS: Correlation
      between the percent diameter stenosis determined by MSCT (78.2+/-13.6%) and QCA
      (76.0+/-14.8%) was significant (P<0.001) but only moderately so (R=0.51). Bland
      Altman analysis revealed no systematic under- or overestimation with MSCT but
      large limits of agreements (+/-27.6%). Also the limits of agreement for
      interobserver agreement (reliability) of MSCT data were considerably large (+/
      24.8%). Among the 27 coronary artery stenoses with a reference diameter of at
      least 3.5 mm, there was improved correlation (R=0.80) and the limits of agreement
      between MSCT and QCA were significantly smaller (+/-17.3%, P<0.008). The
      agreement between MSCT and QCA was not significantly different for stenoses with
      no calcification or only calcium spots (+/-28.2%) as compared with those with
      moderate-or-severe calcifications (+/-27.3%; P=0.8). MSCT allowed correct
      classification of coronary stenoses into low-grade (below 75%) and high-grade
      stenoses (at least 75%), in 62% (73 of 118). CONCLUSIONS: The accuracy and
      reliability of coronary artery stenosis quantification with MSCT using isotropic
      voxel sizes and multisegment reconstruction is still too low to recommend routine
      clinical application because of rather low agreement, correlation, and
      reliability. Despite these limitations, the current results demonstrate the
      potential of MSCT for reliable and accurate quantification of coronary artery
      stenoses in the near future provided that further improvements in spatial and
      temporal resolution will be achieved.

PMID- 17220724
TI  - Cardiovascular safety of gadoterate meglumine (Gd-DOTA).
AB  - OBJECTIVES: Gadolinium complexes are not considered to be a drug class at high
      risk for prolonging cardiac repolarization, which can lead to potentially life
      threatening arrhythmias such as torsade de pointes. However, only limited robust
      data are available on these compounds despite their extensive use as contrast
      enhancers in magnetic resonance imaging. We present an overview of recent
      cardiovascular safety data obtained on gadoterate meglumine (Gd-DOTA). MATERIALS
      AND METHODS: Cardiovascular safety was evaluated by "state-of-the-art"
      nonclinical ex vitro (dog Purkinje fibers) and in vivo studies in both normal
      (dogs) and sensitized animal models (rabbits) and in patients with various
      diseases in a specific clinical trial. RESULTS: In all of these studies, Gd-DOTA
      did not show any direct deleterious effect on cardiac electrophysiology and
      especially on ventricular repolarization. CONCLUSION: These results confirmed the
      good safety profile of Gd-DOTA derived from postmarketing evaluations.
      Nonspecific gadolinium complexes used for magnetic resonance contrast enhancement
      do not constitute a class-at-risk for drug-related arrhythmias.

PMID- 17220726
TI  - Fast retrospectively gated quantitative four-dimensional (4D) cardiac micro
      computed tomography imaging of free-breathing mice.
AB  - OBJECTIVE: We sought to demonstrate retrospectively gated dynamic 3D cardiac
      micro computed tomography (CT) of free-breathing mice. MATERIALS AND METHODS:
      Five C57Bl6 mice were scanned using a cone-beam scanner with a slip-ring-mounted
      flat-panel detector. After the injection of an intravascular iodinated contrast
      agent, projection images were acquired over the course of 50 seconds, while the
      scanner rotated through 10 complete rotations. The mouse respiratory and
      electrocardiogram signals were recorder simultaneously with image acquisition.
      After acquisition, the projection images were retrospectively sorted into
      projections belonging to different cardiac time points, occurring only during
      expiration. RESULTS: Dynamic 3D cardiac images, with isotropic 150-microm voxel
      spacing, were reconstructed at 12-millisecond intervals throughout the cardiac
      cycle in all mice. The average ejection fraction and cardiac output were 58.2+/
      4.6% and 11.4+/-1.3 mL/min, respectively. The measured entrance dose for the
      entire scan was 28 cGy. Repeat scans of the same animals showed that intrasubject
      variability was smaller than intersubject variability. CONCLUSIONS: We have
      developed a high-resolution micro computed tomography method for evaluating the
      cardiac function and morphology of free-breathing mice in acquisition times
      shorter than 1 minute.

PMID- 17220727
TI  - Experimental investigations of nonlinearities and destruction mechanisms of an
      experimental phospholipid-based ultrasound contrast agent.
AB  - OBJECTIVES: We sought to characterize the acoustical behavior of the experimental
      ultrasound contrast agent BR14 by determining the acoustic pressure threshold
      above which nonlinear oscillation becomes significant and investigating
      microbubble destruction mechanisms. MATERIALS AND METHODS: We used a custom
      designed in vitro setup to conduct broadband attenuation measurements at 3.5 MHz
      varying acoustic pressure (range, 50-190 kPa). We also performed granulometric
      analyses on contrast agent solutions to accurately measure microbubble size
      distribution and to evaluate insonification effects. RESULTS: Attenuation did not
      depend on acoustic pressure less than 100 kPa, indicating this pressure as the
      threshold for the appearance of microbubble nonlinear behavior. At the lowest
      excitation amplitude, attenuation increased during insonification, while, at
      higher excitation levels, the attenuation decreased over time, indicating
      microbubble destruction. The destruction rate changed with pressure amplitude
      suggesting different destruction mechanisms, as it was confirmed by granulometric
      analysis. CONCLUSIONS: Microbubbles showed a linear behavior until 100 kPa,
      whereas beyond this value significant nonlinearities occurred. Observed
      destruction phenomena seem to be mainly due to gas diffusion and bubble
      fragmentation mechanisms.

PMID- 17220728
TI  - Evaluation of a novel time-efficient protocol for gadobenate dimeglumine (Gd
      BOPTA)-enhanced liver magnetic resonance imaging.
AB  - OBJECTIVE: We sought to evaluate gadobenate dimeglumine for the detection and
      characterization of focal liver lesions in the unenhanced and already pre
      enhanced liver. MATERIALS AND METHODS: Sixty patients were evaluated
      prospectively. Unenhanced T1-weighted gradient echo (T1wGRE) and T2-weighted
      turbo spin echo (T2wTSE) images were acquired followed by contrast-enhanced
      T1wGRE images during the dynamic, equilibrium, and delayed phases after the bolus
      injection of 0.05 mmol/kg gadobenate dimeglumine. An identical series of dynamic
      images was then acquired after the delayed scan following a second 0.05 mmol/kg
      bolus of gadobenate dimeglumine. Images were evaluated randomly in 2 sessions by
      3 independent blinded readers. Evaluated images in the first session comprised
      the unenhanced images, the first or second set of dynamic images, and the delayed
      images. The second session included the unenhanced images, the dynamic images not
      yet evaluated in the first session, and the delayed images. The 2 reading
      sessions were compared for lesion characterization and diagnosis, and kappa
      (kappa) values for interobserver agreement were determined. Quantitative
      evaluation of lesion contrast enhancement was also performed. RESULTS: The
      enhancement behavior in the second dynamic series was similar to that in the
      first series, although pre-enhancement of the normal liver resulted in reduced
      lesion-liver contrast-to-noise ratios and the visualization of some lesions only
      on arterial phase images. Typical imaging features for the lesions included in
      the study were visualized clearly in both series. Strong agreement (kappa=0.56
      0.89; all evaluations) between the 2 images sets was noted by all readers for
      differentiation of benign from malignant lesions and for definition of specific
      diagnosis, and between readers for diagnoses established based on images acquired
      in the unenhanced and pre-enhanced liver. CONCLUSION: Dynamic imaging in the
      hepatobiliary phase gives similar information as dynamic imaging of the
      unenhanced liver. This might prove advantageous for screening protocols involving
      same session imaging of primary extrahepatic tumors and liver.

PMID- 17220729
TI  - Standardized threshold approach using three-dimensional proton magnetic resonance
      spectroscopic imaging in prostate cancer localization of the entire prostate.
AB  - OBJECTIVES: We sought to determine the localization accuracy using 3-dimensional
      (3D) proton magnetic resonance spectroscopic imaging (MRSI) of the entire
      prostate with a standardized thresholds approach in prostate cancer patients.
      MATERIALS AND METHODS: In a prospective study, 32 consecutive patients were
      examined. Mean age and prostate specific antigen level were 61 years and 7.8
      ng/mL, respectively. Median biopsy Gleason score was 6. T2-weighted MRI and 3D
      MRSI of the entire prostate were performed. Three readers recorded the location
      of suspicious peripheral zone and central gland cancer nodules on a standardized
      division of the prostate (14 regions of interest [ROI]) using a standardized
      thresholds approach. The degree of diagnostic confidence for each ROI was
      recorded on a 5-point scale. Reconstructed whole-mount section histopathology was
      the standard of reference. The sensitivity, specificity, positive, and negative
      predictive value, overall accuracy and interobserver agreement were calculated.
      Areas under the ROI-based receiver operating characteristic curve (AUC) and
      diagnostic performance parameters were determined. RESULTS: The standardized
      thresholds approach had an accuracy of 81% and an AUC of 0.85-0.86 for
      differentiation between benign and malignant ROIs in the peripheral zone and an
      accuracy of 87% and an AUC of 0.86-0.91 for this differentiation in the central
      gland, respectively. Specificities of 81% to 88% were achieved with accompanying
      sensitivities of 75% to 92% for both peripheral zone and central gland,
      respectively. Moderate to near-perfect interobserver agreement was demonstrated
      (kappa=0.42-0.91). CONCLUSION: Our data indicate that a standardized zone
      specific threshold approach in MRSI of the prostate is able to prospectively
      differentiate between benign and malignant tissues in the peripheral zone and the
      central gland with good accuracy and interobserver agreement.

PMID- 17220730
TI  - Low tube voltage improves computed tomography imaging of delayed myocardial
      contrast enhancement in an experimental acute myocardial infarction model.
AB  - OBJECTIVE: We sought to evaluate the influence of tube voltage on the
      visualization of acute myocardial infarction (MI) in cardiac multislice spiral
      computed tomography (MSCT). MATERIALS AND METHODS: Acute MI was induced in 12
      domestic pigs by a 45-minute balloon occlusion of the left anterior descending
      artery. Delayed enhancement magnetic resonance imaging was performed 15 minutes
      after the injection of 0.2 mmol/kg Gd-DTPA. On the same day, retrospectively ECG
      gated MSCT was performed at 120, 100, and 80 kV (16x0.75mm, 550mAseff.) 15
      minutes after the injection of 140 mL of iopromide (1 g/iodine/kg). The pigs were
      killed and the hearts were excised and stained with 2,3,5-triphenyltetrazolium
      chloride. The area of acute MI, contrast-to-noise ratio (CNR), and percent signal
      difference were compared among the different imaging techniques by applying Bland
      Altman plots and 2-way analysis of variance. RESULTS: On MSCT at 120, 100, and 80
      kV, the respective mean acute MI sizes were 18.4+/-11.4%, 19.3+/-11.5%, and
      20.5+/-11.6%. The mean MI sizes were 20.8+/-12.2% and 20.1+/-12.4% on magnetic
      resonance imaging and 2,3,5-triphenyltetrazolium chloride staining. Analysis of
      variance did not show any statistically significant differences between the
      different techniques with respect to the size of acute MI (P=0.9880). Comparing
      the different kV settings on MSCT, the highest percent signal difference (74.7+/
      12.1%) and the highest CNR (6.7+/-1.8) between infarcted and healthy remote
      myocardium were achieved at 80 kV. CONCLUSIONS: When compared with routine scan
      protocols, low tube voltage MSCT allows for the assessment of the MI size with an
      improved CNR and contrast resolution. This technique appears to be advantageous
      for assessing myocardial viability from contrast enhanced late-phase MSCT.

PMID- 17220731
TI  - Comparison between functional magnetic resonance imaging at 1.5 and 3 Tesla:
      effect of increased field strength on 4 paradigms used during presurgical work
      up.
AB  - OBJECTIVES: We sought to evaluate the benefit of 3 T compared with 1.5 T during
      presurgical functional magnetic resonance imaging. MATERIALS AND METHODS: Six
      participants performed a motor, a visual, and 2 language paradigms both at 1.5
      and 3 T. The number of activated voxels, mean t-value, and assessment of language
      dominancy were compared between both field strengths. Group analysis was
      performed to evaluate the influence of field strength on the cortical language
      activation patterns. RESULTS: The number of activated voxels and mean t-values
      were significantly higher at 3 T for all paradigms. Using the same statistical
      threshold, language activation was significantly less lateralized, and more
      activation zones were depicted at 3 T compared with 1.5 T. CONCLUSIONS:
      Sensitivity associated with visual, motor and language functional magnetic
      resonance imaging increased significantly at 3 T. Additional cortical areas were
      depicted during language processing at 3 T. For assessment of language dominancy,
      usage of more stringent statistical thresholds at 3 T is suggested.

PMID- 17220732
TI  - Nephrogenic systemic fibrosis: a review of 6 cases temporally related to
      gadodiamide injection (omniscan).
AB  - OBJECTIVES: Nephrogenic systemic fibrosis (NSF) is a rare acquired disorder that
      was first recognized in 1997. Presented is a retrospective review of 6 cases of
      NSF diagnosed by skin biopsy in our institution during the past 4 years and their
      relationship to gadodiamide exposure. METHODS AND RESULTS: Patient age ranged
      from 23 to 71 years. The onset of symptoms consistent with NSF was between 19
      days and 2 months after gadodiamide exposure. Five patients had severe renal
      impairment and started dialysis around the period of gadodiamide exposure (1 day
      before the 37 days after contrast administration). The sixth patient had a
      clotted access at the time of a contrast-enhanced magnetic resonance venogram and
      was hence not being adequately dialyzed. The dose of gadodiamide ranged from 16
      to 40 mL (0.11 to 0.36 mmol/kg). Despite having normal serum bicarbonate, 5 of
      the 6 patients had an elevated anion gap metabolic acidosis. CONCLUSIONS: In our
      6 patients, all had either failing native or transplant kidneys at the time of
      gadodiamide exposure. The development of NSF was temporally related to
      gadodiamide injection, suggesting as the etiology dechelation of the agent and
      thus emphasizing the need for change in clinical practice.

PMID- 17220733
TI  - Then melancholy, now depression: a modern interpretation of Rembrandt's mental
      state in midlife.
AB  - The authors identify two Rembrandt etchings of 1642, Saint Jerome in a Dark
      Chamber and A Scholar at a Table by Candlelight, as self-portraits. Considered
      with biographical data, the prints suggest that Rembrandt suffered from a bipolar
      personality disorder, manifest in exuberance and lavish spending in the 1630s,
      and then, after the death of the artist's wife, in clinical depression in the
      early 1640s. Depression is depicted in the prints by their dark ambiance, and the
      figure's pose is traditional in art to represent melancholia, one of the four
      classical humors conventionally ascribed to artistic genius. In addition, the
      authors identify as a portrait of his wife the object at which the "scholar" is
      looking. Although the panel is turned away from the viewer of the etching, its
      size, shape, and material suggest that it is a painting that survives in Kassel,
      Germany.

PMID- 17220734
TI  - Diagnosing major depressive disorder XI: a taxometric investigation of the
      structure underlying DSM-IV symptoms.
AB  - Psychopathologists have long debated the latent structure of mental disorders,
      and a number of researchers have suggested that depression may be best
      characterized as a continuous, rather than categorical, phenomenon. Nonetheless,
      attention has been drawn to limitations permeating existing research and the need
      for studies using more appropriate statistical methods developed expressly to
      tease apart taxonic (categorical) and dimensional (continuous) structural models.
      The present study examined the structure underlying the DSM-IV symptoms of major
      depressive disorder in a large outpatient sample rigorously assessed using
      semistructured clinical interviews. The results of a series of taxometric
      procedures and consistency tests supported a taxonic structural model, consistent
      with the only previous taxometric study of DSM-IV symptoms in an adult outpatient
      sample. In addition to the need for further replication and clarification, these
      results have implications for the assessment and diagnosis of major depressive
      disorder. Suggestions for several additional avenues of research are discussed.

PMID- 17220735
TI  - Cross-cultural validation of the DMI-10 measure of state depression: the
      development of a Chinese language version.
AB  - Depression measurement tools in cross-cultural research require careful design
      and thorough validation to ensure that cognitive concepts in one culture can be
      appropriately translated and applied to a differing culture. The aim of this
      study was to validate the Chinese version of a screening measure of state
      depression, the 10-item Depression in Medically Ill (DMI-10), and we report three
      interdependent studies. An initial bilingual test-retest study identified four
      (of the 10) items as having poor cross-cultural validity. A second study involved
      focus groups participants exploring the meaning of translated items with Chinese
      speakers. The third study repeated the bilingual test-retest analyses on the
      modified DMI-10 form and demonstrated improved correlation coefficients on all
      items and an excellent overall correlation (r=0.87) between the Chinese and
      English versions. The Chinese DMI-10 should prove useful as a tool in cross
      cultural research to understand the Chinese experience of depression. The
      findings of this study have methodological implications for cross-cultural
      research on depression.

PMID- 17220736
TI  - Parental control, partner dependency, and complicated grief among widowed adults
      in the community.
AB  - Data from the Yale Bereavement Study, a community-based longitudinal study, were
      used to investigate the association of 192 widowed individuals' recollections of
      parenting affection and control during childhood with dependency on the deceased
      spouse and the development of severe grief symptoms following bereavement. The
      hypothesis that dependency on the deceased spouse mediates the association of
      parental affection and control during childhood with the development of severe
      grief following bereavement was investigated. Findings indicated that a high
      level of perceived parental control during childhood was associated with elevated
      levels of dependency on the deceased spouse and with symptoms of complicated
      grief. Dependency on the deceased spouse mediated the association of perceived
      parental control with the development of complicated grief following bereavement.

PMID- 17220738
TI  - Television watching and the risk of incident probable posttraumatic stress
      disorder: a prospective evaluation.
AB  - The relation between viewing television coverage of a mass disaster and the
      development of posttraumatic stress disorder (PTSD) is poorly understood. A
      cohort of New Yorkers without baseline probable PTSD (N=1787) was assessed 1 year
      following the September 11, 2001, attacks. The primary outcome was new-onset
      probable PTSD assessed through a validated scale, and the primary exposure was
      number of hours of September 11 anniversary news coverage viewed. A total of 99
      (5.6%) of participants had developed probable PTSD at the 1-year follow-up.
      Watching 12 or more hours of September 11 attack anniversary news coverage was
      associated with a 3.4-fold increased risk of new-onset probable PTSD (p=0.004).
      Exposure to television coverage of the September 11 anniversary was associated
      with new-onset probable PTSD among a cohort of New Yorkers with no probable PTSD
      at baseline.

PMID- 17220737
TI  - Psychological distress of rescue workers eight and one-half years after
      professional involvement in the Amsterdam air disaster.
AB  - This study examined specific and general psychological distress 8.5 years
      following the 1992 cargo aircraft crash in Amsterdam. Participants included 334
      occupationally exposed fire fighters and 834 occupationally exposed police
      officers compared with reference groups of 194 fire fighters and 634 police
      officers who were exposed to duty-related stressors other than the disaster. On
      the standardized instruments of psychological distress, exposed fire fighters
      reported more somatic complaints and fatigue, while exposed police officers
      reported higher psychological distress on all aspects. The degree and type of
      exposure at the disaster site and other background factors were associated with
      several outcomes of psychological distress levels of exposed rescue workers. The
      disasters' aftermath of rumors about potential health consequences due to toxic
      exposure likely contributed to the long-lasting psychological distress of some of
      the rescue workers as well.

PMID- 17220739
TI  - Profiling posttraumatic functional impairment.
AB  - Many individuals who have been exposed to psychological trauma suffer from
      impaired functioning, regardless of whether they have PTSD. Our purpose was to
      identify a subset of PTSD symptoms linked to functional impairment to a) improve
      the likelihood that individuals with posttraumatic impairment receive treatment,
      and b) offer a method to assess cost-burden of trauma history in epidemiological
      studies. We examined patterns of trauma-related symptoms in two independent
      community surveys (N=1002 and 630). Rank ordering of symptoms and their
      associations with impairment guided construction of an impairment-related profile
      in the first data set. The profile was then tested in the second data set. The
      derived symptom profile, consisting of intense recollections and/or emotional
      symptoms upon exposure to reminders, plus one or more of numbing/detachment,
      avoidance, sleep problems, concentration problems, or hypervigilance, detected
      the majority (88% and 74%) of persons with posttraumatic functional impairment.
      The symptom profile can help identify traumatized individuals who may benefit
      from treatment but do not necessarily meet criteria for PTSD.

PMID- 17220740
TI  - Trajectory of traumatic stress symptoms in the aftermath of extreme natural
      disaster: a study of adult thai survivors of the 2004 Southeast Asian earthquake
      and tsunami.
AB  - This study investigated the trajectory of traumatic stress symptoms in the
      aftermath of the 2004 Southeast Asian earthquake-tsunami. A total of 265 adult
      Thai survivors were assessed at 2 weeks and 6 months following the earthquake
      tsunami. The percentages of survivors reporting traumatic stress symptoms were
      22% at 2 weeks and 30% at 6 months postdisaster. Four trajectories of traumatic
      stress symptoms were identified: 12% of survivors presented with chronic stress
      symptoms, 18% had a delayed onset, 10% showed improvement, and the remaining 60%
      maintained a stable emotional equilibrium. Among survivors, the chronic group was
      the oldest, the delayed group reported the lowest level of perceived government
      support, and the resilient group experienced the fewest postdisaster psychiatric
      symptoms. Results pointed to the need to broaden the conceptualization of
      postdisaster stress responding as well as to establish disaster psychiatry and
      related mental health activities in the region.

PMID- 17220741
TI  - Positive schizotypy and trauma-related intrusions.
AB  - The current study extends previous investigation of schizotypy as a vulnerability
      factor for trauma-related intrusions through the use of a clinical sample. Fifty
      people seeking psychological interventions after experiencing a distressing or
      traumatic event completed measures of positive schizotypy, posttraumatic stress
      disorder symptomatology, peritraumatic dissociation, and mood. Individuals
      scoring high in positive schizotypy were vulnerable to experiencing more frequent
      trauma-related intrusions along with wider posttraumatic stress disorder
      symptomatology, including hypervigilance, avoidance, and low mood. Results are
      discussed within a theoretical context, suggesting that certain information
      processing styles associated with high schizotype individuals may account for a
      vulnerability to trauma-related intrusions.

PMID- 17220742
TI  - Relationship satisfaction and psychological distress among concerned significant
      others of pathological gamblers.
AB  - This study explores correlates of psychological distress and relationship
      satisfaction among concerned significant others (CSOs) of pathological gamblers.
      CSOs often seek help in dealing with the gambling problem and are influential in
      recovery, but little is known about the sources of their distress. A sample of
      186 CSOs responded to media announcements offering telephone and bibliotherapy
      support. In multivariate models, CSOs who were spouses and who were younger
      reported more personal distress, and higher distress was associated with a
      greater number of CSO emotional and behavioral consequences. Lower relationship
      satisfaction was associated with more CSO emotional consequences, fewer gambler
      consequences, and greater severity of gambling problem. Implications for
      treatment are discussed.

PMID- 17220743
TI  - Association between exposure to childhood and lifetime traumatic events and
      lifetime pathological gambling in a twin cohort.
AB  - The present study seeks to estimate the strength of the association between
      exposure to lifetime traumatic events and gambling problems while accounting for
      the potential contribution of psychiatric disorders, genetic factors, and family
      environmental influences. In 2002, structured diagnostic interviews were
      conducted with 1675 male twins to obtain data on exposure to traumatic events and
      pathological gambling. Multinomial regression tested for associations between
      each traumatic event and three levels of problem gambling (1-2 symptoms, at risk;
      3-4 symptoms, problem gambling, and 5 or more symptoms, pathological gambling).
      Analyses of data from twin pairs discordant for gambling behavior controlled for
      genetic and family environmental factors. After adjustment for covariates, child
      abuse (relative risk [RR]=2.31), child neglect (RR=5.53), witnessing someone
      badly hurt or killed (RR=2.83), and physical attack (RR=3.39) were associated
      with pathological gambling. Genetic and family environmental factors
      significantly contributed to the association between exposure to traumatic events
      and one or more symptoms of problem gambling. Exposure to childhood and lifetime
      traumatic events are significantly associated with problem and pathological
      gambling. These associations are partially accounted for by psychiatric
      covariates and genetic and family environmental factors.

PMID- 17220744
TI  - Reported maltreatment in childhood in relation to the personality features of
      Norwegian adult psychiatric outpatients.
AB  - To explore long-term associations between maltreatment in childhood and
      personality features in adulthood, 160 consecutive adult psychiatric outpatients
      completed self-administered questionnaires. Maltreatment was defined as either
      child abuse or neglect exerted by parents or other adults, coldness and
      overprotection by parents, or bullying by peers. The Childhood Trauma
      Questionnaire was used to detect childhood abuse by parents or other adults,
      while dimensions of parental coldness and overprotection were captured by the
      Parental Bonding Instrument. Bullying by peers was measured by an inventory used
      in schools. Personality variables were covered by the 5-PFa related to the "Big
      Five," The Rosenberg Self-Esteem Scale, and the Locus of Control of Behavior.
      Reports of bullying by peers were linked to poor self-esteem and external locus
      of control. Child maltreatment by parents or other adults were linked to the Big
      Five personality dimensions; bullying by peers was not.

PMID- 17220745
TI  - Impact of supported housing on clinical outcomes: analysis of a randomized trial
      using multiple imputation technique.
AB  - In 1992, the US Department of Housing and Urban Development (HUD) and the US
      Department of Veterans Affairs (VA) established the HUD-VA Supported Housing (HUD
      VASH) Program to provide integrated clinical and housing services to homeless
      veterans with psychiatric and/or substance abuse disorders at 19 sites. At four
      sites, 460 subjects were randomly assigned to one of the three groups: (1) HUD
      VASH, with both Section 8 vouchers and intensive case management; (2) case
      management only; and (3) standard VA care. A previous publication found HUD-VASH
      resulted in superior housing outcomes but yielded no benefits on clinical
      outcomes. Since many participants missed prescheduled visits during the follow-up
      period and follow-up rates were quite different across the groups, we reanalyzed
      these data using multiple imputation statistical methods to account for the
      missing observations. Significant benefits were found for HUD-VASH in drug and
      alcohol abuse outcomes that had not previously been identified.

PMID- 17220746
TI  - Familiarity with mental illness and approval of structural discrimination against
      psychiatric patients in Germany.
AB  - Structural discrimination against psychiatric patients may occur as a result of
      distribution of resources in the health system. We examine whether familiarity
      with mental illness, which reduces discrimination on the individual level, also
      moderates the approval of structural discrimination in health care funding. We
      conducted a representative survey of the German population (N=5025) in 2001 using
      a fully structured personal interview, including a measure of preferences for the
      allocation of health resources and an assessment of familiarity with mental
      illness. The approval of structural discrimination was inversely related to the
      individual's familiarity with mental illness in depression and, to a lesser
      extent, in schizophrenia. This relationship was absent for alcoholism and
      generally weak for contacts to mentally ill persons outside one's own family.
      Strategies successful in reducing individual discrimination are thus not
      necessarily suitable for combating structural discrimination and need to be
      tailored to their specific target.

PMID- 17220747
TI  - Gender differences in bipolar disorder type 1: a 48-week prospective follow-up of
      72 patients treated in an Italian tertiary care center.
AB  - To explore gender differences in bipolar I disorder, we compared the longitudinal
      treatment outcome and baseline demographic and clinical characteristics of 27
      male and 45 female adult subjects who were treated for an acute affective episode
      and longitudinally followed for a period of up to 48 weeks. Females were more
      likely to report a history of suicidal gestures and a comorbid panic disorder;
      males were more likely to present with a comorbid obsessive-compulsive disorder,
      and there was a trend for a more frequent history of alcohol or substance abuse.
      No significant differences were found between the genders for the time to
      remission from the index episode, number of recurrences, and time spent with any
      clinical or subclinical mood symptom during the 48 weeks of maintenance
      treatment. Although differences may exist between bipolar I male and female
      subjects, prospective course does not seem to reveal differences in a 48-week
      period, at least when similar treatment strategies are adopted.

PMID- 17220751
TI  - Pulmonary arteriovenous malformations in hereditary hemorrhagic telangiectasia: a
      series of 126 patients.
AB  - Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized
      by epistaxis, telangiectasia, and visceral vascular manifestations. Infectious
      and ischemic central nervous system (CNS) manifestations due to embolism through
      pulmonary arteriovenous malformations (PAVMs) represent the main causes of
      morbidity. To improve the phenotypic characterization of HHT with PAVM, we
      conducted a retrospective multicenter study of patients with HHT and at least 1
      PAVM detected by chest computed tomography (CT) and/or pulmonary angiography,
      with particular attention to CNS and infectious manifestations. The study
      included 126 patients (47 men, 79 women), with a mean age of 43.1 +/- 17.4 years;
      45 patients had a mutation of the ENG gene and 16 had a mutation of ACVRL1. PAVMs
      were diagnosed as a result of systematic screening procedures (29%), incidental
      imaging findings (15%), dyspnea (22%), or CNS symptoms (13%). The PAVMs were
      diagnosed at a mean age of 43 +/- 17 years, with a linear distribution of
      diagnosis between 20 and 75 years. Dyspnea on exertion was present in 56% of
      patients. Four patients had a hemothorax, including 1 during pregnancy. Fifty
      three CNS events directly related to HHT (excluding migraine) were observed in
      35% of patients: cerebral abscess (19.0%), ischemic cerebral stroke (9.5%),
      transient cerebral ischemic attack (6.3%), and cerebral hemorrhage (2.4%). The
      median age of onset was 33 years for cerebral abscesses (range, 11-66 yr), and
      53.5 years for ischemic cerebral events (range, 2-72 yr). Migraine was reported
      in 16% of patients. The diagnoses of PAVM and HHT were made at the time of the
      cerebral abscess in 13 cases (54%). Forty-three percent of patients were
      hypoxemic at rest. Contrast echocardiography showed intrapulmonary right-to-left
      shunting in 87% of tested patients. PAVMs were seen on chest radiograph in 54% of
      patients, and on the CT scan in all patients. One hundred five patients (83%)
      underwent treatment of the PAVM, by percutaneous embolization (71%) and/or by
      surgical resection (23%). A high frequency of CNS and infectious complications
      was observed in this large series of patients with HHT-related PAVM. Physicians
      may not be sufficiently aware of the clinical manifestations of this orphan
      disorder. Patients diagnosed with HHT should be informed by physicians and
      patient associations of the risk of PAVM-related complications, and systematic
      screening for PAVM should be proposed, regardless of a patient's symptoms,
      familial history, or genetic considerations.

PMID- 17220752
TI  - Fever after a stay in the tropics: diagnostic predictors of the leading tropical
      conditions.
AB  - Differential diagnosis of fever in travelers returning from the tropics is
      extremely diverse. Apart from the travel destination, other diagnostic predictors
      of tropical infections are poorly documented in returning travelers. From April
      2000 to December 2005, we prospectively enrolled all patients presenting at our
      referral centers with fever within 1 year after visiting a tropical or
      subtropical area. For clinical relevance, the diagnostic predictors of the
      leading tropical conditions were particularly investigated in the febrile
      episodes occurring during travel or within 1 month after return (defined as early
      onset fever). In total, 2071 fever episodes were included, occurring in 1962
      patients. Most patients were western travelers (60%) or expatriates (15%).
      Regions of exposure were mainly sub-Saharan Africa (68%) and southern
      Asia/Pacific (14%). Early-onset fever accounted for 1619 episodes (78%). Most
      tropical infections were related to specific travel destinations. Malaria (mainly
      Plasmodium falciparum) was strongly predicted by the following features: enlarged
      spleen, thrombocytopenia (platelet count <150 x 10(3)/microL), fever without
      localizing symptoms, and hyperbilirubinemia (total bilirubin level >or=1.3
      mg/dL). When malaria had been ruled out, main predictors were skin rash and skin
      ulcer for rickettsial infection (mainly African tick bite fever); skin rash,
      thrombocytopenia, and leukopenia (leukocyte count <4 x 10(3)/microL) for dengue;
      eosinophil count >or=0.5 x 10(3)/microL for acute schistosomiasis; and enlarged
      spleen and elevated alanine aminotransferase level (>or=70 IU/L) for enteric
      fever. The initial clinical and laboratory assessment can help in selecting
      appropriate investigations and empiric treatments for patients with imported
      fever.

PMID- 17220753
TI  - A prospective multicenter study on fever of unknown origin: the yield of a
      structured diagnostic protocol.
AB  - We conducted a prospective study to update our knowledge of fever of unknown
      origin (FUO) and to explore the utility of a structured diagnostic protocol. From
      December 2003 to July 2005, 73 patients with FUO were recruited from 1 university
      hospital (n = 40) and 5 community hospitals (n = 33) in the same region in The
      Netherlands. FUO was defined as a febrile illness of >3 weeks' duration, a
      temperature of >38.3 degrees C on several occasions, without a diagnosis after
      standardized history-taking, physical examination, and certain obligatory
      investigations. Immunocompromised patients were excluded. A structured diagnostic
      protocol was used. Patients from the university hospital were characterized by
      more secondary referrals and a higher percentage of periodic fever than those
      referred to community hospitals. Infection was the cause in 16%, a neoplasm in
      7%, noninfectious inflammatory diseases in 22%, miscellaneous causes in 4%, and
      in 51%, the cause of fever was not found (no differences between university and
      community hospitals). There were no differences regarding the number and type of
      investigations between university and community hospitals. Significant predictors
      for reaching a diagnosis included continuous fever; fever present for <180 days;
      elevated erythrocyte sedimentation rate, C-reactive protein, or lactate
      dehydrogenase; leukopenia; thrombocytosis; abnormal chest computed tomography
      (CT); and abnormal F-fluorodeoxyglucose positron emission tomography (FDG-PET).
      For future FUO studies, inclusion of outpatients and the use of a set of
      obligated investigations instead of a time-related criterion are recommended.
      Except for tests from the obligatory part of our protocol and cryoglobulins in an
      early stage, followed by FDG-PET, and in a later stage by abdominal and chest CT,
      temporal artery biopsy in patients aged 55 years or older, and possibly bone
      marrow biopsy, other tests should not be used as screening investigations.

PMID- 17220754
TI  - Disseminated tuberculosis: a 10-year experience in a medical center.
AB  - Disseminated tuberculosis remains a diagnostic challenge because the
      presentations are nonspecific. In the current retrospective study we describe the
      clinical characteristics and outcome of disseminated tuberculosis. From January
      1995 to December 2004, patients with culture-confirmed tuberculosis who fulfilled
      the criteria for disseminated tuberculosis were selected and their medical
      records reviewed. Their clinical isolates were genotyped. Of the 3058 patients
      with culture-confirmed tuberculosis, 164 (5.4%) had disseminated disease; 14.0%
      of patients had acquired immunodeficiency syndrome. The most common radiographic
      finding was miliary lung lesions (47.0%); 31.1% of patients died at the end of
      the study. Poor prognostic factors included hypoalbuminemia, hyperbilirubinemia,
      renal insufficiency, and delayed antituberculosis treatment. Clinical findings
      suggestive of disseminated tuberculosis were miliary lung lesions, serum ferritin
      >1000 microg/L, infiltrative liver disease, and adjusted calcium >2.6 mmol/L.
      Simultaneously performing mycobacterial culture and histopathologic examination
      of bone marrow biopsy was more sensitive and faster than just performing
      mycobacterial blood culture in diagnosing disseminated tuberculosis. Of the 64
      preserved Mycobacterium tuberculosis isolates, 47 (73.4%) were clustered and 27
      (42.2%) were Beijing family. Since prognosis was worse in patients with delayed
      treatment, a high index of suspicion is required, especially in those with
      clinical findings suggestive of disseminated tuberculosis.

PMID- 17220755
TI  - Emphysematous cystitis: illustrative case report and review of the literature.
AB  - Emphysematous cystitis is a rare disease characterized by primary infection of
      the urinary bladder with gas-producing pathogens. There is a paucity of
      information on this entity in the English-language literature covering the last
      45 years, and the clinical picture is poorly outlined. We carried out a
      comprehensive, retrospective review of the English-language literature from 1986
      to 2006, searching for reports describing cases of emphysematous cystitis. The
      demographic, clinical, laboratory, imaging, and outcome characteristics of every
      eligible patient were excerpted. In the present report, we describe a typical
      case of emphysematous cystitis, followed by an analysis of the literature. Of the
      53 eligible cases, most were elderly women with diabetes mellitus (62.2%).
      Classic symptoms of urinary tract infection were present in only 53.3% of cases.
      Abdominal tenderness and hematuria were noted in 65.6% and 82.3% of cases,
      respectively. Plain abdominal X-ray was highly sensitive (97.4%), while abdominal
      computerized tomography was the most sensitive and specific diagnostic tool. A
      complicated course attributable to emphysematous cystitis was described in 18.8%
      of cases. The exact mechanism contributing to the formation of gas in such cases
      is unknown. Various theories have been suggested, including fermentation of
      glucose in urine, with emphasis on disequilibrium between gas formation and
      clearance. Emphysematous cystitis has a highly variable presentation and course,
      with a considerable potential for complications. Further diagnostic imaging is
      highly recommended in diabetic patients with urinary tract infection who present
      with abdominal pain and hematuria. Knowledge of this rare entity may lead to
      early diagnosis and appropriate management.

PMID- 17220756
TI  - Catheter-related Staphylococcus aureus bacteremia in cancer patients: high rate
      of complications with therapeutic implications.
AB  - Risk factors for complications of catheter-related Staphylococcus aureus
      bacteremia (CRSAB) have been studied in the general patient population but have
      not been well defined in cancer patients. We investigated potential risk factors
      for intravascular and extravascular complications in these patients. We
      retrospectively reviewed the records of patients with CRSAB hospitalized at our
      institution between January 2001 and December 2004. Demographic, clinical,
      laboratory, and microbiologic characteristics were extracted for the period of
      hospitalization and up to 3 months thereafter. Intravascular complications were
      defined as infective endocarditis and/or septic thrombosis. Extravascular
      complications included septic arthritis, deep tissue abscess, osteomyelitis,
      septic pulmonary emboli, septic shock, and CRSAB-related death. Ninety-one
      patients were included in the current study; 63% had solid tumors and the
      remainder had hematologic malignancies. The incidence of overall complications
      was 40% (n = 36); 19% (n = 17) were intravascular. On multivariate analysis,
      renal failure was associated with an increased risk of overall complications
      (odds ratio [OR], 12.78; 95% confidence interval [CI], 1.43-114.29; p = 0.0226).
      Patients with solid tumors were more likely to have intravascular complications
      (OR, 5.47; 95% CI, 1.11-27.01; p = 0.04369). Risk factors for extravascular
      complications included hematologic malignancy (OR, 9.56; 95% CI, 2.36-38.77; p =
      0.0016) and female sex (OR, 5.25; 95% CI, 1.2-22.99; p = 0.0279). Renal failure
      is a risk factor for CRSAB complications in patients with cancer. Patients with
      solid tumors and CRSAB tend to develop intravascular complications, while
      patients with hematologic malignancies are prone to develop extravascular
      complications. Hence consideration should be given to extending the duration of
      therapy beyond 2 weeks.

PMID- 17220758
TI  - 5 steps to jump start faculty research.
AB  - Many new nursing leaders assuming deanships or assistant or interim deanships
      have limited education, experience, or background to prepare them for the job. To
      assist new deans and those aspiring to be deans, the authors of this department,
      2 deans, offer survival tips based on their personal experiences and insights.
      They address common issues, challenges, and opportunities that face academic
      executive teams, such as negotiating an executive contract, obtaining faculty
      lines, building effective work teams, managing difficult employees, and creating
      nimble organizational structure to respond to changing consumer, healthcare
      delivery, and community needs. The authors welcome counterpoint discussions with
      readers.

PMID- 17220759
TI  - Student perceptions of the impact of double testing.

PMID- 17220760
TI  - The podium as a stage: a one-woman act.

PMID- 17220761
TI  - Writing context-dependent item sets that reflect critical thinking learning
      outcomes.
AB  - Faculty in a medical-surgical nursing course developed learning outcomes to
      foster critical thinking skills involved in clinical reasoning. To facilitate
      students' abilities to make effective clinical judgments, direct teaching of
      thinking skills was incorporated into nursing content instruction. This
      instructional design challenged faculty to develop test items that would permit
      direct observation of students' thought processes. The author describes how
      context-dependent item sets were developed to meet this evaluation need.

PMID- 17220762
TI  - How to read, interpret, and understand evidence-based literature statistics.
AB  - To implement best practices through research utilization, nurses need to read,
      interpret, and understand literature formatted with evidence-based practice
      language and statistics. Hypothetical examples highlight 7 terms and their
      formulas. A scenario to personally calculate such evidence-based practice
      statistics can be used to enhance personal effectiveness and to teach others.

PMID- 17220763
TI  - Educating a new generation: teaching baby boomer faculty about millennial
      students.
AB  - This review examines the impact of generational influences on the faculty-student
      relationship. Specifically, the baby boomer faculty-millennial learner dyad is
      explored, as these two generations are most representative of the faculty-student
      demographic. Teaching and learning preferences are emphasized, and implications
      and recommendations for nursing faculty are presented.

PMID- 17220764
TI  - Friday night in the pediatric emergency department: a simulated exercise to
      promote clinical reasoning in the classroom.
AB  - High acuity in client populations has placed increasing demands on novice nurses
      to apply concepts of clinical reasoning to nursing practice. To assist nursing
      students in developing clinical reasoning skills, an exercise called "Friday
      Night in the Pediatric Emergency Department" was designed to give students real
      time experiences in triage situations using a simulated clinical experience in a
      classroom setting. The author describes the exercise and its impact on the
      clinical reasoning skills of undergraduate nursing students.

PMID- 17220765
TI  - The curriculum vitae sending the right message.
AB  - When reviewing curriculum vitae (CV), it becomes clear that some CV information
      provides a better reflection of work completed than others do. The authors
      provide a description of common CV errors, propose strategies to avoid such
      problems, and suggest methods for developing an accurate and clear CV that
      highlights accomplishments and clearly represents the work. Tips for updating CV
      and suggestions for electronic formats are also provided.

PMID- 17220766
TI  - Joy stealing: 10 mean games faculty play and how to stop the gaming.
AB  - This article opens with an exemplar of Wendy, a nurse educator, whose exuberance
      is drained by conflicted relationships with faculty colleagues. Corroborating
      Wendy's story are 10 joy-stealing faculty games that surfaced from the
      spontaneous writings of 261 nurse educators attending the National League for
      Nursing's 2005 Summit. Educational research that describes the sociopolitical
      context and the psychoemotional fallout from such games elucidates why turning
      nurse educators into passionate scholars may stop the gaming.

PMID- 17220767
TI  - Tracking clinical use of personal digital assistant reference resources.
AB  - Mechanisms are needed to evaluate the effectiveness of ever-increasing
      technological resources for nursing student use. The authors tracked the use of
      personal digital assistants versus textbook resources by junior-level
      baccalaureate nursing students throughout 1 semester. The authors discuss the
      results of that activity and provide a starting point for the evaluation of the
      use of personal digital assistants by nursing students.

PMID- 17220768
TI  - Longitudinal evaluation of a live interactive video baccalaureate nursing
      program.
AB  - Beginning with a brief history of a community-inspired distance education
      initiative, the authors describe how one college of nursing offers an entire
      generic bachelor of science in nursing program over live interactive video for
      nursing students at 2 distance sites. The 10-year longitudinal evaluation of
      student and program outcomes is presented. Student and program success is
      evidenced by congruence of grades and National Council Licensure Exam (NCLEX)
      pass rates between sites.

PMID- 17220769
TI  - Paraxial optics of astigmatic systems: relations between the wavefront and the
      ray picture approaches.
AB  - PURPOSE: The paraxial propagation of astigmatic wavefronts through astigmatic
      optical systems can be described by the augmented step-along method (ASAM). Its
      equivalence to the linear ray optics approach is considered in detail. METHODS:
      The ASAM is exploited to derive paraxial ray paths through a general coaxial
      astigmatic system. RESULTS: Starting from the information inherent in the ASAM
      all 2x2 submatrices rendering the general 4x4 transference of linear optics can
      be generated. This proves the complete equivalence of both approaches.
      Additionally, we show that the symplectic relations are automatically obeyed in
      the ASAM. CONCLUSIONS: The ASAM offers a complete alternative to describe the
      paraxial optics of astigmatic optical systems. According to the ASAM, an optical
      system is fully characterized by the back vertex vergence and the angular
      magnification matrix. Hence, a complete description of the paraxial optics of an
      eye should not only report the state of refraction but the angular magnification
      matrix as well, although it is not yet very common. The magnification matrix
      might be important in cases of anisometropia or the design of progressive
      addition lenses. Yet, a simple clinical procedure to determine the angular
      magnification matrix is missing.

PMID- 17220771
TI  - The academy and future change.

PMID- 17220774
TI  - Reading with optical magnifiers: page navigation strategies and difficulties.
AB  - PURPOSE: To read efficiently with a simple hand or stand magnifier, people with
      visual impairment have to move (navigate) the device along each line (forward
      phase) and back to the correct position at the start of the next line (retrace
      phase). Page navigation difficulties have been implicated as limiting factors
      when reading with hand and stand magnifiers, but have not been objectively
      measured. METHODS: Magnifier movements were recorded using a 3SPACE Isotrak
      system for 43 participants with age-related macular degeneration (AMD) who read
      two short stories using their habitual hand or stand magnifier. Page navigation
      was quantified in terms of magnifier movements and navigation errors for the
      forward and retrace phases. Visual acuities and visual fields were measured, and
      magnifier usage and page navigation difficulties were surveyed. RESULTS: During
      the forward phase, participants primarily used either a straight (47%) or
      diagonal downward (46%) movement, whereas during the retrace phase, the majority
      (56%) used a downward movement. On average, forward navigation time was four
      times longer than retrace navigation time (p<0.001). The most common navigation
      error was incorrect positioning of the magnifier at the end of the retrace
      movement. Near word acuity correlated strongly with forward time (r=0.78), and
      moderately with retrace time (r=0.53) and forward errors (r=0.50). Vertical field
      of view correlated with retrace errors (r=-0.53). Participants' estimates of page
      navigation difficulties were not predictive of objective measures of performance.
      CONCLUSIONS: We quantified page navigation strategies and difficulties of people
      with AMD reading with magnifiers. Retrace, which presents the most common
      difficulty, is not well predicted by vision measures or magnifier
      characteristics; future studies should investigate the relationship between motor
      skills and navigation performance, and the impact of training or devices on
      reducing retrace navigation difficulties.

PMID- 17220775
TI  - Myopia prevalence in Chinese-Canadian children in an optometric practice.
AB  - PURPOSE: The high prevalence of myopia in Chinese children living in urban East
      Asian countries such as Hong Kong, Taiwan, and China has been well documented.
      However, it is not clear whether the prevalence of myopia would be similarly high
      for this group of children if they were living in a Western country. This study
      aims to determine the prevalence and progression of myopia in ethnic Chinese
      children living in Canada. METHODS: Right eye refraction data of Chinese-Canadian
      children aged 6 to 12 years were collated from the 2003 clinical records of an
      optometric practice in Mississauga, Ontario, Canada. Myopia was defined as a
      spherical equivalent refraction (SER) equal or less than -0.50 D. The prevalence
      of myopia and refractive error distribution in children of different ages and the
      magnitude of refractive error shifts over the preceding 8 years were determined.
      Data were adjusted for potential biases in the clinic sample. A questionnaire was
      administered to 300 Chinese and 300 Caucasian children randomly selected from the
      clinic records to study lifestyle issues that may impact on myopia development.
      RESULTS: Optometric records of 1468 children were analyzed (729 boys and 739
      girls). The clinic bias adjusted prevalence of myopia increased from 22.4% at age
      6 to 64.1% at age 12 and concurrently the portion of the children that were
      emmetropic (refraction between -0.25 and +0.75 D) decreased (68.6% at 6 years to
      27.2% at 12 years). The highest incidence of myopia for both girls (
      approximately 35%) and boys ( approximately 25%) occurred at 9 and 10 years of
      age. The average annual refractive shift for all children was -0.52+/-0.42 D and 
      0.90+/-0.40 D for just myopic children. The questionnaire revealed that these
      Chinese-Canadian children spent a greater amount of time performing near work and
      less time outdoors than did Caucasian-Canadian children. CONCLUSIONS: Ethnic
      Chinese children living in Canada develop myopia comparable in prevalence and
      magnitude to those living in urban East Asian countries. Recent migration of the
      children and their families to Canada does not appear to lower their myopia risk.

PMID- 17220776
TI  - Optic disc tomography and perimetry in controls, glaucoma suspects, and early and
      established glaucomas.
AB  - PURPOSE: To analyze the priority of morphological and functional defects in
      glaucoma. METHODS: Nine-hundred seventy-three eyes of 973 subjects were examined
      with Heidelberg retinal tomograph (HRT II) and Octopus 311 perimeter (TOP
      strategy). These included 72 controls (C), 659 early and suspect open angle
      glaucoma (ESG) with perimetric mean defect (MD) lower than 6 dB, and 242
      confirmed moderate and advanced glaucomas (AG) with perimetric MD>or=6 dB.
      RESULTS: I. (Control group): Age was significantly correlated with mean
      sensitivity (MS) (r=0.50, p<0.00001) and nasal cup shape measure (r=0.33,
      p=0.005). II. (C and ESG groups): For 95.8% specificity, the best sensitivity was
      obtained with square root of loss variance (sLV) (ROC area=69.7%,
      sensitivity=33.7%) and maximum contour elevation (ROC area=69.6%,
      sensitivity=29.0%). Maximum contour elevation and sLV coincided in diagnosis in
      12.4% of cases. An equation using 64 HRT II indices predicted MS with a standard
      error of estimate (SEE) of 1.87 dB (r=0.67, p<0.00001) and MD (SEE=1.88 dB,
      r=0.47, p<0.00001). III. (All cases): RB discriminant function value was the best
      HRT II index to estimate MS values (SEE=5.4 dB, r=0.52, p<0.0001), MD (SEE=5.2
      dB, r=0.50, p<0.0001), sLV (SEE=1.9 dB, r=0.41, p<0.0001) and Number of
      Pathological Points (NPP; SEE=21.3 dB, r=0.49, p<0.0001). Sector correlation of
      the optic nerve and visual field was high (maximum r=0.66) in cases with superior
      visual field defects and low in the rest of cases. More than 95% of cases with
      established glaucoma had abnormal sLV, but <60% had abnormal optic disc indices.
      DISCUSSION: Perimetry reveals age-related defects slightly more than HRT II. HRT
      II indices correlated better with MS than with MD, probably because none of them
      was age corrected. Good correlation between anatomical and functional data in C
      and ESG, and sensitivity results indicated small differences in early development
      between both methods. Perimetry identifies defects more clearly than structural
      measures in established glaucoma.

PMID- 17220777
TI  - Changes of ocular higher order aberration in on- and off-eye of rigid gas
      permeable contact lenses.
AB  - PURPOSE: To investigate ocular higher order aberration (HOA) changes caused by
      rigid gas permeable (RGP) contact lens (CL) wear. METHODS: Twenty-two eyes of 22
      myopic patients and 14 eyes of 14 keratoconic patients who were fitted with an
      RGP CL were enrolled to examine ocular HOAs using a Hartmann-Shack wavefront
      sensor before and after RGP wear. Root mean square (RMS) values and Zernike
      coefficients in RGP-on and RGP-off eyes were compared for both myopic and
      keratoconic eyes, or between patient groups divided according to their prefitted
      total HOA value (RMS<0.33 microm or>or=0.33 microm in myopic eyes and RMS<0.46
      microm or>or=0.46 microm in keratoconic eyes). All HOA values were recomputed for
      a 4-mm pupil for comparison purposes. RESULTS: In keratoconic eyes, RGP CL
      changed the direction of vertical coma from -0.185 to 0.134 microm (p=0.024). In
      the low HOA myopic group, total HOA increased from 0.23 to 0.35 microm (p=0.006)
      by RGP CL wear, mainly due to increased coma aberration from 0.0951 to 0.2146
      microm (p=0.006). The direction of vertical coma changed from the inferior to
      superior cornea in the low HOA group (p=0.020). In the high HOA keratoconic
      group, total HOA decreased from 0.54 to 0.36 microm (p=0.049), and the direction
      of the vertical coma changed from the inferior to superior cornea (p=0.049).
      CONCLUSIONS: RGP CL wear may enhance or reduce HOA based on original existing
      ocular aberration mainly through directional changes in vertical coma.

PMID- 17220778
TI  - Regional repeatability measures of corneal thickness: Orbscan II and ultrasound.
AB  - PURPOSE: To compare repeatability of the measures of corneal thickness obtained
      by slit-scanning light method (Orbscan II) with those obtained by an ultrasound
      pachymeter, with special interest in the peripheral region of the cornea.
      METHODS: On 24 normal adults, aged 20 to 58 years (average 36 years) with up to 
      8.5 DS refractive error, three measures of corneal thickness were taken using
      Orbscan II and then by ultrasound pachymetry (under topical anesthesia with
      benoxinate 0.4%). The Orbscan central sample zone of 1 mm was selected, or the
      numerical maps were used to extract single point data along the horizontal
      corneal meridian to the nasal and temporal sides out to 4.5 mm. Ultrasound
      readings were taken from the central cornea and at the periphery just inside the
      limbus (4.5 mm from center) with a 2.4-mm diameter probe. RESULTS: For a central
      1-mm diameter zone, the coefficient of variation (CV) for three consecutive
      corneal thickness measures was 0.81%+/-0.44%, but was marginally higher
      (p=0.004), if just the central single point data was taken with Orbscan (0.86%+/
      0.45%). Similar repeatability was noted for the numerical output across the
      temporal side along the horizontal meridian out to 2.5 mm from the center, but
      farther out to 4 mm and on the nasal side the repeatability was slightly less and
      around 1.0% (p<0.001). Orbscan point readings of thickness could only sometimes
      be obtained at 4.5 mm temporally (with a poorer CV of 1.32%) and very rarely at
      4.5 mm on the nasal side. No absolute differences in Orbscan repeatability were
      noted when comparing emmetropic with myopic subjects (p>or=0.5). Ultrasound
      pachymetry readings across the central zone were repeatable to 0.82%+/-0.67%.
      When measured with the edge of the ultrasound probe just touching the limbus, the
      repeatability of ultrasound readings was 1.37%+/-1.10% temporally and 1.49%+/
      1.02% nasally, but neither was statistically worse that the most peripheral
      readings for Orbscan (p>or=0.210). However, it was also noted that the absolute
      values of corneal thickness, even with the application of the 0.92 acoustic
      factor, were 0.010 mm greater for Orbscan at the center and 0.040 mm in the
      corneal periphery. CONCLUSIONS: Orbscan II provides the clinician with a
      repeatable noninvasive method of measuring corneal thickness that is not
      necessarily any better than ultrasound pachymetry, and should not be considered
      as interchangeable with that for ultrasound.

PMID- 17220779
TI  - Nomogram, corneal topography, and final prescription relations for corneal
      refractive therapy.
AB  - PURPOSE: To analyze the relationships between the first diagnostic lens and the
      lens finally prescribed for corneal refractive therapy with Paragon CRT and to
      correlate them with corneal topography, and refractive parameters. METHODS: The
      files of 86 patients who were successfully fitted with corneal refractive therapy
      using Paragon CRT were reviewed. Differences between diagnostic vs. finally
      prescribed lens parameters of base curve radius (BCR), return zone depth (RZD)
      and landing zone angle (LZA), as well as the number of lenses required to achieve
      the final fit were correlated with corneal topographic parameters and attempted
      refraction. RESULTS: There were statistically significant differences between CRT
      parameters for the first lens suggested by the nomograms and the lens finally
      prescribed (Wilcoxon signed ranks, p<0.05). On average, those changes did not
      achieve 1 full step difference (i.e., 0.10 mm for BCR and 25 microm for RZD).
      Only LZA achieved a full step change (1 degrees). According to our data, 92% of
      the fittings were achieved by changing only two parameters or less. The majority
      of changes required were within+/-1 step of the initially selected (96% for BCR,
      99% for RZD, and 100% for LZA). Changes in lens parameters are related with some
      ocular parameters, but mainly with first lens parameters. RZD was the parameter
      requiring more changes. The amount of change in RZD was correlated with steep
      keratometry, BCR, and RZD of the first lens. CONCLUSIONS: Nomograms used for lens
      selection with Paragon CRT have a high first-fitting success with a relatively
      simple fitting procedure. Correlations between final lens parameters and ocular
      and initial lens parameters obtained in this study can assist clinicians to
      anticipate the level of difficulty in achieving optimal fitting with Paragon CRT
      sigmoid contact lens for corneal refractive therapy and the most frequent changes
      needed to achieve it.

PMID- 17220780
TI  - A pre-application drop containing carboxymethylcellulose can reduce multipurpose
      solution-induced corneal staining.
AB  - PURPOSE: Use of polyhexanide based multipurpose solutions (MPSs) for contact lens
      disinfection has been linked to low-grade corneal staining. In vitro data suggest
      that carboxymethylcellulose (CMC) may neutralize polyhexanides. The purpose of
      this investigation was to determine whether a pre-application drop of CMC reduces
      polyhexanide staining in vivo. METHODS: Thirty adapted soft contact lens (SCL)
      wearers participated in this investigator-masked, randomized, two-way cross-over
      study. Subjects wore a new Group II lens (alphafilcon A, 66% water) daily for 4
      weeks and disinfected lenses using a MPS containing 0.0001% polyaminopropyl
      biguanide. A lens lubricant containing either CMC or povidone as the primary
      viscolyzer was applied to the lens each day before lens wear. Biomicroscopic
      signs and symptomatology were assessed. The difference in scores, 0 to 4 weeks
      and the difference between lubricants were analyzed. RESULTS: The cumulative
      fluorescein staining scores for combined eyes demonstrated a significant increase
      over time (e.g., cumulative staining score; p=0.004 and p<0.001 for CMC and
      povidone, respectively, matched pairs t-test, two-tailed), suggesting that for
      both lubricants the staining worsened with wear. This effect was expected and
      likely driven by the MPS. However, the mean cumulative staining scores for CMC
      and povidone were 2.8 and 2.6 out of 20 possible at baseline, increasing to 4.9
      and 7.1 at 4 weeks, respectively. The increases were significantly different
      (p=0.003, matched pairs t-test, two-tailed) suggesting a greater increase in
      corneal staining for the povidone lubricant. The symptom scores were not
      significantly different, 0 to 4 weeks by regimen or between preinstillation
      drops. CONCLUSIONS: These results suggest that a CMC-containing preapplication
      drop can reduce corneal staining resulting from disinfection with a polyhexanide
      MPS. This result is consistent with a proposed mechanism for CMC to neutralize
      cationic disinfectants and may offer clinicians another means to reduce this type
      of corneal staining.

PMID- 17220781
TI  - Current status of transplantation of the small intestine.
AB  - The evolution of small bowel transplantation has been significant over the past
      20 years to the point at which it can now be considered a viable and often
      successful option in the treatment of many forms of short bowel syndrome. A
      refinement of surgical techniques, improved immunosuppression, enhanced
      understanding of gut immunology, and better treatment and prevention of
      complications have contributed to a marked improvement in graft and patient
      survival. Whereas this transplant population is still beset with many potential
      complications after isolated bowel or multivisceral transplantation and long-term
      graft survival (like with other solid organ transplants) remains a challenge, the
      future holds promise for a continuation of the current positive trend of
      improvement in several areas.

PMID- 17220782
TI  - Factors influencing the collagenase digestion phase of human islet isolation.
AB  - Substantial advances in human islet isolation technology have occurred during the
      past decade. However, it is still difficult to recover the entire quantity of
      islets contained in a pancreas. A major obstacle to successful human islet
      isolation has been the variability of the collagenase digestion phase of islet
      isolation. Future advances in enzyme technology will make it possible to
      optimally liberate islets with enzyme blends "tailor-made" for each individual
      donor pancreas. Such innovative strategies will be advantageous in improving
      islet isolation efficiency, recovery, viability, and ultimately posttransplant
      function.

PMID- 17220783
TI  - A population-based study of cancer incidence in solid organ transplants from
      donors at various risk of neoplasia.
AB  - A population-based cohort study of recipients of organs from donors with a
      recognized history or active cancer has been conducted by linking the Italian
      National Registry of Transplanted Patients and the National Registry of Donors
      with Neoplasia Risk. Between 2002 and 2004, 8,198 solid organ transplants have
      been performed in Italy, 108 of them with organs from 59 cadaveric donors with
      various risk of neoplasia. There were two reported cases of nonmelanoma skin
      cancer during the follow up of the transplanted patients, which lasted 27.6+/
      11.3 months (234 patient-years). In our study, recipients of organs from donors
      with various degree of neoplasia risk are exposed to a low risk of cancer
      transmission.

PMID- 17220784
TI  - Why nondocumented residents should have access to kidney transplantation:
      arguments for lifting the federal ban on reimbursement.
AB  - Current U.S. legislation restricts reimbursement for organ transplantation for
      nondocumented residents, which makes it difficult for many immigrants, including
      children, to access the transplants they need. In this article, we offer moral,
      economic, and legal reasons that nondocumented immigrants deserve the same access
      to kidney transplantation as do legal residents. We argue that the current
      reasoning for such a ban is based on unjustified fears and unsupported
      assumptions, which are not a solid basis for determining eligibility for
      lifesaving therapy for the neediest members of our society.

PMID- 17220785
TI  - Illegal aliens are not entitled to federally funded organ transplants.

PMID- 17220786
TI  - Effect of exenatide on beta cell function after islet transplantation in type 1
      diabetes.
AB  - BACKGROUND: Islet transplantation can reduce or eliminate the need for insulin in
      patients with type 1 diabetes. Exenatide is a long acting analogue of Glucagon
      like peptide-1 (GLP-1) that augments glucose induced insulin secretion, and may
      increase beta cell mass. We evaluated the effect of exenatide on insulin
      secretion after islet transplantation. METHODS: Eleven C-peptide positive islet
      cell recipients with elevated glucose levels were treated with exenatide for
      three months. Response was assessed by insulin requirements, meal tolerance
      tests, and hyperglycemic glucose clamps. RESULTS: Ten patients responded to
      exenatide. Two patients who had not restarted insulin achieved good glycemic
      control and one patient who had received 5500 IE/kg in first islet infusion was
      able to stop insulin. Seven other patients decreased their insulin dose by 39% on
      exenatide. Hyperglycemic clamp studies showed a rise in second phase insulin
      release (before exenatide: 246+/-88 pM; during exenatide: 644+/-294 pM, P<0.01).
      Meal tolerance studies before and one month after stopping exenatide did not show
      a difference in glucose or C-peptide values. Nausea and vomiting were the major
      side effects. CONCLUSIONS: Exenatide stimulates insulin secretion in islet
      transplant recipients. It reduces insulin dose in some patients and may delay the
      need to resume insulin in others. We did not find any evidence of a trophic
      effect on islets.

PMID- 17220787
TI  - Determinants of insulin resistance in renal transplant recipients.
AB  - BACKGROUND: Insulin resistance is considered to play an important role in the
      development of cardiovascular disease, which limits long-term renal transplant
      survival. Renal transplant recipients are more insulin-resistant compared with
      healthy controls. It is not known to date which factors relate to this excess
      insulin resistance. Therefore, we investigated which factors are related to
      insulin resistance long-term after renal transplantation. METHODS: All renal
      transplant recipients at our outpatient clinic with a functioning graft for more
      than one year were invited to participate. We excluded diabetic recipients.
      Recipient, donor, and transplant characteristics were collected as putative
      determinants. We used fasting insulin, homeostasis model assessment index, and
      McAuley's index as valid estimates of insulin resistance. Linear regression
      models were created to investigate independent determinants of all indexes.
      RESULTS: A total of 483 recipients (57% male, 50+/-12 years) were analyzed at a
      median (interquartile range) time of 6.0 (2.6-11.6) years posttransplant. The
      most consistent determinants across all three indices were body mass index
      (P<0.001), waist-to-hip ratio (P<0.001), and prednisolone dose (P<0.05).
      Independent associations were present for total cholesterol (P<0.001), high
      density lipoprotein cholesterol (P<0.001), creatinine clearance (P<0.05),
      recipient age (P<0.001), and gender (P< or =0.002). No independent associations
      were present for transplant-related factors such as acute rejection treatment or
      cytomegalovirus seropositivity. CONCLUSIONS: Our results indicate that obesity,
      distribution of obesity, and prednisolone treatment are the predominant
      determinants of insulin resistance long term after transplantation. Insulin
      resistance after renal transplantation could be managed favorably by weight and
      prednisolone dose reduction, which may reduce cardiovascular disease.

PMID- 17220788
TI  - Polycystic kidney disease is a risk factor for new-onset diabetes after
      transplantation.
AB  - BACKGROUND: Data from matched historical cohort studies suggest that autosomal
      dominant polycystic kidney disease (ADPKD) may be a risk factor for new-onset
      diabetes after transplantation (NODAT). METHOD: A retrospective study of 429
      renal allografts transplanted from 1990 through 2004 in nondiabetic patients was
      performed. A multivariate analysis of risk factors for NODAT was performed with
      focus on ADPKD. RESULTS: A total of 6.5% of all patients developed NODAT and a
      further 11% developed impaired glucose tolerance. NODAT developed in 13.4% of
      patients with ADPKD compared with 5.2% of non-ADPKD patients (P=0.01). There were
      significant univariate associations between NODAT and recipient age (P=0.001) and
      weight (P<0.0001). There was no association between NODAT and recipient gender,
      human leukocyte antigen mismatch, acute rejection, or cumulative
      methylprednisolone dose. In a multivariate analysis, ADPKD was a strong risk
      factor for the development of NODAT (odds ratio [OR]=2.41, P=0.035) after
      correction for recipient age, weight, gender, ethnicity, and tacrolimus use. Age
      (OR=1.06), weight (OR=1.04), and nonwhite race (OR=5.04) were the other
      significant variables. CONCLUSION: We conclude that ADPKD is a significant risk
      factor for the development of NODAT. This may influence the follow up and
      management choices of these patients in the future.

PMID- 17220789
TI  - Comparison of laparoscopic versus hand-assisted live donor nephrectomy.
AB  - BACKGROUND: The aim of the present study was to compare hand-assisted
      laparoscopic live donor nephrectomy with the classic laparoscopic method, using
      meta-analytical techniques. METHODS: A literature search was performed for
      studies comparing hand-assisted laparoscopic nephrectomy with classic
      laparoscopic nephrectomy for live kidney donation between 1999 and 2005. The
      following end points were evaluated: operative time, warm ischemia time,
      intraoperative adverse events, donor and recipient postoperative complications,
      and length of hospital stay. RESULTS: Nine comparative studies matched the
      selection criteria, reporting on 376 patients, of whom 202 (53.7%) had hand
      assisted laparoscopic nephrectomy and 174 (46.3%) had the classic laparoscopic
      technique. Conversion to open surgery was 2.97% in the hand-assisted group and
      4.60% in the laparoscopic group (P=0.35). Total operative and warm ischemia times
      were significantly shorter for hand-assisted laparoscopy by 30.03 minutes
      (P=0.02) and 1.14 minutes (P<0.001), respectively. The intraoperative blood loss
      was less for the hand-assisted laparoscopy group by 34.16 mL (P=0.008), although
      intraoperative (3.46% vs. 7.47%; P=0.24) and postoperative (5.94% vs. 10.34%;
      P=0.30) donor complications and recipient complications (including delayed graft
      function and primary nonfunction, 8.41% vs. 7.42%; P=0.32) were similar between
      the hand-assisted and laparoscopic groups. CONCLUSION: Hand-assisted laparoscopic
      nephrectomy appeared to have the same donor and recipient complication rate with
      standard laparoscopy but offered substantial advantages in terms of shortened
      operative and warm ischemia time as well as decreased intraoperative bleeding.

PMID- 17220790
TI  - Mycophenolate mofetil and C-reactive protein in renal transplant recipients.
AB  - BACKGROUND: C-reactive protein (CRP) is a strong predictor of cardiovascular
      disease, all-cause mortality, and renal allograft loss. Little is known about the
      effects of immunosuppressive and cardiovascular risk-modifying drugs on CRP in
      renal transplant recipients. METHODS: We retrospectively identified stable
      patients with > or =1 highly sensitive CRP measurements between January 1 and
      August 31, 2005. Variables collected included patient demographics; transplant,
      dialysis, and cardiovascular disease-related variables; and medication profiles.
      Univariate correlations with CRP were assessed by unpaired Student t testing,
      analysis of variance, or chi analysis and followed by multivariate linear
      regression with stepwise backward elimination until a final stable model was
      attained. RESULTS: CRP levels were obtained in 298 recipients. In univariate
      analysis, body mass index (P<0.0001) and systolic blood pressure (P=0.009) showed
      a positive correlation, whereas number of immunosuppressive drugs (P=0.05) and
      use of mycophenolate mofetil (MMF) (P=0.003) were negatively correlated with CRP
      levels. By multivariate analysis, only body mass index (P<0.0001) and MMF dose
      (P<0.0001) were independently and opposingly correlated with CRP. Mean CRP level
      was 5.18+/-5.7 mg/L in patients not taking MMF compared with 3.13+/-3.5 mg/L in
      those on 2000 mg per day (P=0.002). CONCLUSIONS: MMF use correlates inversely
      with CRP levels in renal transplant recipients, suggesting that immunosuppressive
      regime design may alter allograft and cardiovascular disease risk in these
      patients. Prospective study of the effects of MMF on novel cardiovascular disease
      risk factors such as CRP is warranted.

PMID- 17220791
TI  - Analysis of HLA class I specific antibodies in patients with failed allografts.
AB  - BACKGROUND: The goals of this study are first to determine the epitope
      specificity of donor specific antibody (DSA) in the serum of alloimmunized
      transplant patients with a failed renal graft; and second to understand the
      correlation between the development of DSA and nondonor specific antibody (NDSA).
      METHODS: The sera of 35 pretransplant panel reactive antibody (PRA)-negative
      patients with failed allografts were examined with single-antigen (SA) luminex
      beads to identify human leukocyte antigen (HLA)-A and -B antibodies. Potential
      HLA antibody epitopes were identified by using computer software and verified by
      absorption and elution from single-antigen cell lines. RESULTS: Twenty-seven
      patients developed donor-specific HLA-A and/or -B antibodies, while the remaining
      eight patients had only nondonor-specific HLA-A and/or -B antibodies. The DSA
      positive patients also had a long list of NDSA. Sixty-eight percent of the
      reactions found in 27 recipients with DSA were attributable to 66 epitopes on the
      mismatched donor HLA molecule. All 39 NDSA in eight patients with only NDSA
      shared 17 epitopes within positive allele specificities. By absorption and
      elution using recombinant cell lines having a single HLA specificity, we
      confirmed the epitopes involved in three patients. CONCLUSION: Development of
      most NDSA in patients with failed allografts is likely due to sharing epitopes
      with DSA and/or other NDSA.

PMID- 17220792
TI  - Genomewide expression profiles of rat model renal isografts from brain dead
      donors.
AB  - BACKGROUND: It has been well documented that two factors, brain death (BD) and
      ischemia/reperfusion (I/R) injury, have distinct but overlapping adverse
      influences on the clinical outcome of renal transplantation. METHOD: We
      previously established a rat model of renal isografting from brain dead donors.
      In the present study, we performed genomic expression profiling with a high
      density oligonucleotide microarray to identify genes that were upregulated or
      downregulated by BD and/or I/R injury. RESULTS: Among a total of 20,550 genes,
      most of those upregulated by BD were genes for adhesion molecules and cytokines
      or for chemokines such as Gro1 and IP-10. When overexpression of these genes was
      assessed by real-time reverse transcriptase-polymerase chain reaction, it was
      only observed one hr after the engraftment of kidneys from BD donors and returned
      to baseline thereafter, indicating the presence of an acute systemic inflammatory
      response to BD. Analysis of biologic networks demonstrated the activation of
      specific pathways that were clearly different for BD and I/R injury. The p53 and
      NFkappaB pathway was involved in the acute response to BD, whereas the Myc, Jun,
      and c-fos pathway was involved in I/R injury. Investigation of secretory protein
      genes identified LCN2 and SPP1 as candidate genes for biologic markers.
      CONCLUSION: Because our experimental system is a good model of renal
      transplantation from brain dead or living human donors, our data may be useful
      for elucidating the pathologic processes involved and for identification of novel
      markers for graft dysfunction of renal transplantation.

PMID- 17220796
TI  - 'Prope' tolerance in a noncompliant living related small bowel transplant
      recipient after severe rejection.
AB  - Advances in immunosuppression and surgical technique have greatly improved
      patient outcomes after intestinal transplantation. However, the procedure remains
      one of the most challenging among solid organ transplantation as a result of the
      high rate of acute rejection, sepsis, and posttransplantation lymphoproliferative
      disorder. Recently, clinical trials to explore tolerance protocols in humans have
      been initiated, including small bowel transplant recipients, with results not
      always reproducible. The concept of operational tolerance is more meaningful in
      the clinical setting when physiological stability of graft function is achieved
      in the absence of maintenance immunosuppression. We report the intriguing case of
      a living related small bowel transplant recipient who developed clinical "prope"
      tolerance to the graft after treatment of severe acute rejection despite
      continuous noncompliance with immunosuppressive therapy.

PMID- 17220794
TI  - Mesenchymal stem cells inhibit dendritic cell differentiation and function by
      preventing entry into the cell cycle.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) play a crucial role in hematopoietic
      development and have been shown to exert a powerful immunosuppressive effect. In
      this study, we investigated the effect of bone marrow MSC on the differentiation
      and function of peripheral blood monocytes into dendritic cells (DCs). METHODS:
      Human MSCs, generated from normal bone marrow, were added to peripheral blood
      monocytes stimulated in vitro with granulocyte-macrophage colony stimulating
      factor and interleukin-4 to become DCs. Monocytes were then examined for the
      expression of markers characteristic of DCs and their ability to stimulate
      allogeneic T cells. In addition, the effect of MSCs on the cell cycle of monocyte
      derived DCs and the expression of various cell cycle proteins were analyzed by
      cytometric analysis and Western blotting with specific antibodies. RESULTS: MSCs
      blocked the differentiation of monocytes into DCs and impaired their antigen
      presenting ability. This resulted from a block of monocytes from entering the G1
      phase of the cell cycle with a progressive number of cells accumulating in the G0
      phase. Cyclin D2 was downregulated. However, differently from what was observed
      in T-cells stimulated in the presence of MSCs, the expression of p27 was found
      decreased, suggesting the involvement of similar but not identical pathways.
      CONCLUSIONS: We conclude that MSCs impair monocyte differentiation and function
      by interfering with the cell cycle. These findings imply that MSC-induced
      immunosuppression might be a side product of a more general antiproliferative
      effect.

PMID- 17220797
TI  - Increased incidence of cytomegalovirus retinitis after allogeneic hematopoietic
      stem cell transplantation.
AB  - Six cases of cytomegalovirus retinitis (CMVR) after allogeneic hematopoietic stem
      cell transplantation were diagnosed between 2002 and 2005 in our center, whereas
      only one case was diagnosed between 1985 and 2001. Cumulative incidence reaches
      2.2%, whereas this complication has been rarely described after hematopoietic
      stem cell transplantation. We aimed to describe clinical and biologic features of
      CMVR and search for risk factors associated with CMVR. CMVR was diagnosed on
      specific funduscopic examination in all patients either on visual symptoms (n=3)
      or on systematic ophthalmologic examination (n=3). CMVR occurred in the context
      of unrelated transplantation in patients with profound immune defect and multiple
      episodes of cytomegalovirus (CMV) reactivation. The combination of a CMV
      seropositive recipient and CMV-seronegative donor was the leading risk factor.

PMID- 17220798
TI  - Complete reversal of glycogen hepatopathy with pancreas transplantation: two
      cases.
AB  - Glycogen hepatopathy is the pathological overloading of hepatocytes with glycogen
      that is associated with poorly controlled diabetes mellitus. Clinically, it
      presents with abdominal discomfort, tender hepatomegaly and elevated
      transaminases. In this report, we describe our experience with two cases of type
      I diabetes mellitus and glycogen hepatopathy. The patients underwent isolated
      pancreas transplantation, following which, we have been able to demonstrate
      complete histological resolution of glycogen hepatopathy associated with control
      of glucose metabolism.

PMID- 17220799
TI  - Gene expression of porcine lymphotrophic herpesvirus-1 in miniature Swine with
      posttransplant lymphoproliferative disorder.
AB  - Porcine lymphotropic herpesvirus-1 (PLHV-1) is a gamma-herpesvirus related to
      Epstein-Barr virus (EBV) and associated with development of posttransplant
      lymphoproliferative disorder (PTLD) following allogeneic stem cell or spleen
      transplantation in miniature swine. Oligonucleotide microarrays were designed
      based on known open reading frames (ORFs) of PLHV-1. Expression was compared by
      cohybridization of cDNA from lymph nodes of PLHV-1+ swine after allogeneic spleen
      transplantation between either: 1) PTLD-affected and PTLD-unaffected swine; or 2)
      PTLD-affected swine vs. samples from the same animal prior to diagnosis. In PTLD
      affected animals, consistent upregulation (nine ORFs) and downregulation (four
      ORFs) of PLHV-1 mRNA was observed in comparison to those without PTLD. No
      differences in gene expression were discovered at the time of clinical PTLD
      diagnosis compared to six to nine days prior to diagnosis in the same animals.
      This model provides insights into the pathogenesis of PTLD and, by extension,
      potential diagnostic and therapeutic tools for human EBV-associated PTLD.

PMID- 17220800
TI  - The effect of trophic factor supplementation on cold ischemia-induced early
      apoptotic changes.
AB  - We have previously shown that trophic factor supplementation (TFS) of University
      of Wisconsin (UW) solution enhanced kidney viability after cold storage. Here, we
      use an in vitro model to study the effect of TFS on early apoptotic changes after
      cold ischemic storage. Mitochondrial membrane potential was determined by
      fluorescence intensity in primary canine kidney tubule cells, Madin-Darby canine
      kidney cells, and human umbilical vein endothelial cells. In addition, caspase 3
      enzyme activity assay and immunofluorescence staining were performed to evaluate
      apoptosis. There was a 15% increase in mitochondrial membrane potential in human
      umbilical vein endothelial cells stored in trophic factor supplemented University
      of Wisconsin solution after four-hour rewarming (P<0.05). TFS suppressed caspase
      3 enzyme activity and activation in human umbilical vein endothelial cells. We
      confirmed that the presence of TFS in UW solution has a beneficial effect by
      protecting mitochondrial function and reducing early apoptotic changes in
      vascular endothelial cells.

PMID- 17220801
TI  - A pooled analysis of posttransplant survival following combined heart-liver
      transplantation.
AB  - Because no single center has accumulated a large experience with this complex
      operation, the effectiveness of combined orthotopic heart transplantation (OHT)
      and orthotopic liver transplantation (OLT) in achieving long-term survival has
      been unknown. Cases of OHT-OLT were pooled from a U.S. transplant recipient
      registry and from previously published literature. Aggregate data from these
      sources was used for survival analysis. Thirty-six patients having undergone OHT
      OLT were listed in the national registry; the one- and five-year patient survival
      rates of these patients were 88% and 78%, respectively. Many patients remain
      alive at 8+ years after transplantation. An analysis of the pooled results of
      previously-published cases estimated a one-year patient survival rate of 84%. In
      selected disease processes, OHT-OLT can correct underlying metabolic
      deficiencies. While rarely indicated, OHT-OLT is a successful treatment for
      patients with end-stage heart and liver disease, with survival comparable to that
      seen after isolated orthotopic heart or orthotopic liver transplantation.

PMID- 17220802
TI  - Successful rescue of refractory, severe antibody mediated rejection with
      splenectomy.
AB  - Antibody-mediated rejection (AMR) commonly occurs after transplantation of ABO
      incompatible and sensitized renal transplant. Treatment regimens commonly include
      a combination of plasmapheresis (PL) and intravenous immunoglobulin (IVIG).
      However, some cases of AMR remain refractory to treatment. We report a case
      series of four patients with AMR refractory to standard therapy (ST) who resolved
      after splenectomy. Four living donor kidney transplant recipients were diagnosed
      with AMR. Two patients were ABO incompatible, one was cross-match positive and
      one had no obvious predisposing factors. After failure of therapy with
      corticosteroids, PL, IVIG, Thymoglobulin, and Rituximab (three patients) or
      Campath (one patient), AMR was treated with laparoscopic splenectomy. After an
      average of 11 days of ST, laparoscopic splenectomy was performed for rescue. The
      urinary output improved immediately in all patients, serum creatinine levels
      decreased within 48 hr, and ABO titers fell in the ABO-incompatible patient and
      the cross-match became negative in the two sensitized patients. Splenectomy may
      play a role in the treatment of AMR refractory to ST.

PMID- 17220803
TI  - High incidence of delayed renal graft function.

PMID- 17220804
TI  - Failure of IL-8 induction in pre-implantation cadaveric biopsies.

PMID- 17220805
TI  - Large granular lymphocyte leukemia after renal transplantation: an immunologic,
      immunohistochemical, and genotypic study.

PMID- 17220806
TI  - Pretransplant bilirubin concentration does not correlate with early reperfusion
      injury following liver transplantation.

PMID- 17220807
TI  - Transplantation of en bloc pediatric kidneys when the proximal vascular cuff is
      too short.

PMID- 17220808
TI  - Sirolimus does not reduce receptor-mediated endocytosis of albumin in proximal
      tubule cells.

PMID- 17220809
TI  - Donor DNA is present in recipient tissues after grafting also in graft-versus
      host disease-free individuals.

PMID- 17220810
TI  - Osteotome technique for removal of symptomatic ear canal exostoses.
AB  - OBJECTIVES/HYPOTHESIS: This study was undertaken to assess a transcanal osteotome
      technique for removing symptomatic ear canal exostoses. Outcome measures included
      healing rates and the rate of complications. STUDY DESIGN: Prospective study in a
      private practice. METHODS: A straight 1-mm osteotome and a curved 1-mm osteotome
      were used by way of a transcanal approach to incrementally remove obstructive ear
      canal exostoses. If anterior or superior bone growths were closely approximating
      the tympanic membrane, they were partially removed with a 1.5 mm cylindrical end-
      and side-cutting burr. Healing rates were monitored with weekly postoperative
      visits. RESULTS: Two hundred twenty-one ear canals (140 patients) were
      consecutively treated with this technique. Healing was achieved at 2 to 8
      (average 3.50) weeks, with 90% healed by 4 weeks. There were 4 mobilizations of a
      full-thickness segment of anterior bony canal wall; 3 exposures of periosteum
      anterior to the anterior bony wall; 1 tear of the tympanic membrane requiring a
      tympanoplasty; 18 anterior and 11 posterior tympanic membrane tears that healed
      spontaneously; 3 instances of sensorineural hearing decrease; 3 cases of new
      onset postoperative tinnitus; and 1 instance of postoperative positioning
      vertigo. There were no lacerations of the tympanic membrane by an osteotome, no
      facial nerve injuries, no soft tissue stenoses of an ear canal, and no skin
      grafting of an ear canal. CONCLUSIONS: The described technique of using
      osteotomes transcanal for removal of symptomatic obstructive ear canal exostoses
      promoted rapid healing and was effective and safe.

PMID- 17220811
TI  - Contact-tracing outcomes among male syphilis patients in Fulton County, Georgia,
      2003.
AB  - OBJECTIVES: Contact tracing may be less effective in populations with casual sex
      partners such as male syphilis patients who report sex with men; this opinion is
      widely held, but few quantitative comparisons are available. GOAL: The goal of
      this study was to compare contact-tracing outcomes among male syphilis patients
      reporting sex with men (MSM) or with women only (MSWO). STUDY DESIGN: The authors
      conducted a record review of cases of early syphilis among MSM and MSWO comparing
      contact-tracing outcomes. RESULTS: Interviews of MSM case-patients resulted in
      higher mean numbers of contacts named and located per case than interviews of
      MSWO. Mean numbers of contacts of MSM and MSWO diagnosed with syphilis per case
      were not significantly different. The mean number of unlocatable sex partners per
      case was slightly higher for MSM than MSWO. CONCLUSION: This study comparing
      contact tracing by the same trained health department personnel demonstrated that
      outcomes of contact tracing were similar for MSM and MSWO.

PMID- 17220813
TI  - Low-dose doxycycline (Oracea) for rosacea.

PMID- 17220812
TI  - Analysis of the operational costs of using rapid syphilis tests for the detection
      of maternal syphilis in Bolivia and Mozambique.
AB  - OBJECTIVE: The objective of this study was to compare the costs of antenatal
      syphilis screening with the rapid plasma reagin (RPR) test and the
      immunochromatographic strip (ICS) test in low-resource settings. GOAL: The goal
      of this study was to assess the costs of introducing rapid syphilis tests to
      reduce maternal and congenital syphilis. STUDY DESIGN: Cost data were collected
      from participating study hospitals and antenatal clinics during 4 field visits to
      the 2 countries in 2003 and 2004. Health utilization outcome data on the number
      of women screened and treated routinely during the demonstration projects were
      used with unit cost data to estimate the incremental costs and average cost per
      woman screened and treated for maternal syphilis. RESULTS: In Mozambique, the
      average cost per woman screened was U.S. $0.91 and U.S. $1.05 for the RPR and ICS
      tests, respectively. In Bolivia, the average cost of screening was U.S. $1.48 and
      U.S. $1.91 using the RPR and ICS test, respectively. In health centers without
      laboratories, the cost per woman screened using the ICS test ranged from U.S.
      $1.02 in Mozambique to U.S. $2.84 in Bolivia. CONCLUSIONS: It is feasible to
      introduce rapid syphilis testing in settings without laboratory services at a
      small incremental cost per woman screened. In settings with laboratories, the
      cost of ICS is similar to that of RPR.

PMID- 17220814
TI  - Dasatinib (Sprycel) for CML and Ph + ALL.

PMID- 17220816
TI  - Poststress left ventricular ejection fraction is an independent predictor of
      major cardiac events in patients with coronary artery disease and impaired left
      ventricular function.
AB  - AIM: The aim of this study was to investigate the prognostic value of myocardial
      perfusion and function SPECT imaging in patients with coronary artery disease
      (CAD) and poor left ventricular (LV) function. METHODS: We studied 261 patients
      (231 men, age 66+/-10 years) with CAD and a resting LV ejection fraction (LVEF)
      <or= 40% assessed during myocardial gated SPECT. Perfusion defect extent was
      calculated using 4D-MSPECT software (Michigan University). Ischemia scoring was
      performed visually. Considered end points were: 1) major adverse cardiac events
      (MACE) (cardiac death, non-fatal myocardial infarction or late
      revascularization), 2) MACE or the need for hospitalization due to heart failure
      (MACE-HF) and 3) cardiac death or non-fatal myocardial infarction. RESULTS:
      During a median follow-up of 31 months, 52 patients (20%) died (35 cardiac
      deaths), 50 (19%) developed a MACE and 69 (26%) a MACE-HF. In a clinical model,
      diabetes and angina status were the only predictors of MACE (chi-squared=19.3;
      P<0.001). By multivariate analysis, poststress LVEF (chi-squared-gain of 6.4;
      P=0.008) and presence of ischemia (chi-squared-gain of 5.8; P=0.018) were
      predictive of MACE. Similarly, diabetes mellitus (chi-squared=12.1; P<0.001),
      poststress LVEF (chi-squared-gain of 5.5; P=0.019) and presence of ischemia (chi
      squared-gain of 4.3; P=0.044) were independent predictors of MACE-HF. Diabetes
      mellitus (chi-squared=17.8; P<0.001), presence of angina complaints (chi-squared
      gain of 6.8; P=0.028) and poststress LVEF (chi-squared-gain of 6.3; P=0.008) were
      independent predictors of cardiac death or non-fatal myocardial infarction.
      CONCLUSION: In patients with impaired LV function and CAD, poststress LVEF is an
      independent predictor of future cardiac events.

PMID- 17220817
TI  - 99mTc-HMPAO and 99mTc-ECD brain uptake correlates of verbal memory in Alzheimer's
      disease.
AB  - AIM: Technetium-99m hexamethylpropylene amine oxime ((99m)Tc-HMPAO) and
      technetium-99m N,N-1,2-ethylene diylbis-Lcysteine diethyl ester dihydrochloride
      ((99m)Tc-ECD) SPECT are widely used in Dementia Clinics for early and
      differential diagnosis. They have been shown to perform differently in
      Alzheimer's disease (AD), but the impact of such differences on both research and
      clinical work is unknown. We investigated the differences between the 2 compounds
      in research work by assessing correlation between performance on a verbal memory
      task and cerebral perfusion in 2 matched groups of AD patients. METHODS: Nineteen
      pairs of patients with mild to moderate AD undergoing SPECT with either 99mTc
      HMPAO or (99m)Tc-ECD were retrospectively selected in a Memory Clinic. Patients
      were matched for sex, age (+/-3 years) and the Mini-Mental State Examination
      score (+/-2 points) with a case-control procedure, thus obtaining 2 well-matched
      groups. The score on the Grober-Buschke selective reminding test (SRT) was
      correlated with SPECT in each group by means of statistical parametric mapping 99
      (height threshold: P<0.01). RESULTS: (99m)Tc-HMPAO SPECT yielded 3 significant
      correlation clusters involving inferior and middle frontal gyri, para-hippocampal
      gyrus and putamen in the right hemisphere; the middle and superior temporal gyri,
      insula and claustrum in the left hemisphere. (99m)Tc-ECD gave a significant
      cluster of correlation in left postcentral gyrus and inferior parietal lobule.
      CONCLUSION: (99m)Tc-HMPAO SPECT correlation sites seem more consistent than
      (99m)Tc-ECD ones with the neurophysiological models of verbal memory, as designed
      both in normal individuals and in pathological conditions. The demonstration of
      such relevant differences introduces a source of variability among studies
      performed with either of the 2 compounds, which must be considered when
      interpreting results.

PMID- 17220819
TI  - Hepatobiliary scintigraphy and gamma-GT levels in the differential diagnosis of
      extrahepatic biliary atresia.
AB  - AIM: The aim of this paper is to identify extrahepatic biliary atresia (EHBA) as
      the cause of cholestasis in neonates with prolonged jaundice and thus accelerate
      the decision for surgical intervention, which is critical for prognosis. METHODS:
      We retrospectively studied 21 infants (13 girls, 8 boys) aged 2-16 weeks who have
      undergone( 99m)Tc-mebrofenin iminodiacetate ((99m)Tc-BrIDA) scintigraphy. They
      were referred because of direct hyperbilirubinemia and jaundice persisting beyond
      the 2nd postnatal week. They had received phenobarbitone premedication prior to
      scintigraphy. Dynamic images for 30 min and then static images (if required) at
      1, 2 and 24 h postinjection were acquired. Images were evaluated visually and
      semiquantitatively, by calculating the liver-to-heart (L/H) ratio. Age, L/H
      ratios, and serum gamma glutamyl transpeptidase (gamma-GT) levels were compared
      (Mann-Whitney U test) between infants with EHBA (Group A) and infants without
      (Group B). The L/H ratios were correlated with age in each group and with gamma
      GT in the entire population. RESULTS: A total of 7/21 infants were classified in
      Group A and 14/21 in Group B. The L/H ratios were significantly lower in Group A.
      The correlation between L/H ratio and age was negative in EHBA and positive in
      non-atretic infants. The gamma-GT levels were inversely correlated with the L/H
      ratios in the entire population, being significantly higher in Group A.
      CONCLUSION: In long-standing neonatal direct hyperbilirubinemia, (99m)Tc-BrIDA
      scintigraphy and the L/H ratio index seem to give useful information in the
      differential diagnosis of EHBA, especially when associated with markedly elevated
      serum gamma-GT levels.

PMID- 17220820
TI  - Pulmonary clearance of aerosolized 99mTc-DTPA in sarcoidosis I patients.
AB  - AIM: Sarcoidosis frequently affects the lungs of patients. Pulmonary clearance
      scintigraphy with Technetium-99m-diethylenetriaminepentaacetic acid ((99m)Tc
      DTPA) aerosol may assess pulmonary involvement of sarcoidosis patients. The study
      investigated early pulmonary involvement of sarcoidosis I patients by assessing
      the pulmonary clearance of inhaled (99m)Tc-DTPA aerosol and the character of
      pulmonary clearance though systemic steroid therapy. METHODS: The pulmonary
      clearance of (99m)Tc-DTPA aerosol was investigated in 24 patients with suspected
      stage I sarcoidosis and 20 non-smoking healthy controls over 18 months. The
      radiological finding was evaluated by chest computed radiography (CR) and high
      resolution computed tomography (HRCT) and the histological diagnosis was
      performed by transbronchial lung biopsy and/or Scalen node biopsy. The
      sarcoidosis I patients with ocular involvement underwent 1 year-systemic steroid
      therapy and were followed up over totally 18 months. RESULTS: The histological
      diagnosis was proved in 13 out of the 24 patients that had no lung filed
      involvement on CR and HRCT. Accelerated pulmonary clearance of (99m)Tc-DTPA was
      observed in 10 out of the 13 sarcoidosis I patients. Nine out of 13 sarcoidosis I
      patients underwent systemic steroid therapy due to ocular involvement and the
      accelerated pulmonary clearance responded to therapy and improved in all of the 9
      over 18 months. CONCLUSIONS: Acceleration of (99m)Tc-DTPA pulmonary clearance may
      be observed in sarcoidosis I patients and the acceleration will respond to
      systemic steroid therapy. Pulmonary clearance scintigraphy with (99m)Tc-DTPA
      aerosol may be useful for assessing pulmonary involvement before radiological
      changes emerge and sarcoidosis I patients with accelerated pulmonary clearance
      may undergo systemic steroid treatment.

PMID- 17220821
TI  - 99mTc-HYNIC Annexin-V imaging of tumors and its relationship to response to
      radiotherapy and/or chemotherapy.
AB  - AIM: The aim of this study was to report on the relationship between
      preradiotherapy and prechemotherapy 99mTc-HYNIC Annexin-V tumor uptake values,
      reflecting ongoing apoptosis, and outcome to radiotherapy and/or chemotherapy.
      METHODS: Twenty-three cancer patients underwent staging examinations and a 99mTc
      HYNIC Annexin-V scintigraphy and subsequent radiotherapy and/or chemotherapy.
      Tumor-to-background ratios derived from tomographic 99mTc-HYNIC Annexin-V images
      were related to treatment outcome as assessed by RECIST criteria. RESULTS: Six
      patients underwent radiotherapy or radiochemotherapy: 4 exhibited response to
      treatment, 1 had stable, and 1 progressive disease. Corresponding tumor-to
      background ratio's were respectively >or=2.3 (in responders), 1.2 in the patient
      presenting with stable disease and 1 in the patient presenting with progressive
      disease. Seventeen patients were treated by chemotherapy alone: 8 were
      progressive, 1 patient presented with stable disease and 8 responded to
      treatment. In 1/8 progressive patients a tumor-to-background ratio of 1.4 was
      found, the others showed no uptake. In the patient presenting with stable disease
      a ratio of 0.1 was found. In the 8 responders, 7 patients had a tumor-to
      background ratio >or=1.3 whereas in 1 patient a ratio of 0.3 was found. Tumor-to
      background ratios in responders (complete plus partial) (median 2.5, range: 0.3
      4.2) were significantly higher when compared to those obtained in non-responders
      (stable plus progressive disease) (median 1, range: 0.1-1.4) (P<0.001).
      CONCLUSION: The findings presented suggest that 99mTc-HYNIC Annexin-V
      pretreatment uptake may be useful to predict response to chemo- and radiotherapy.

PMID- 17220822
TI  - Impact of instrumentation on DaTSCAN imaging: how feasible is the concept of
      cross-systems correction factor?
AB  - AIM: The aim of this investigation was to study the impact of applying different
      camera emission computed tomography (ECT) systems on semi-quantitative analysis
      of the novel dopamine transporter (DaT) radioligand [123I]-ioflupane (DaTSCAN)
      and whether applying a system-dependent correction factor is feasible to allow a
      migration of a ''normal'' reference data set between systems. METHODS: Two triple
      head systems, PrismXP-3000 equipped with high resolution Fan-Beam (PRISM) and
      Irix (Philips Medical Systems, Europe) equipped with high resolution parallel
      whole collimators (IRIX), were compared in phantom and patient studies.
      Acquisition and quantification parameters were standardized. The anthropometric
      striatal calibration phantom (RSD Inc., CA, USA) at rising striatum: background
      ratios between 2-11 was studied. Fifty-one consecutive patients (25 females, age
      64.5+/-11.9 years, and 26 males, age 60.6+/-12.7 years) were randomized to both
      cameras for acquisition time typically beginning 3.5 to 4.5 h after i.v.
      injection of 123I-Joflupane at 2.06+/-0.47 MBq/kg. Striatal uptake of the
      radioligand was categorized as normal or abnormal, and abnormal images were
      further subdivided into 3 severity levels. Striatum: cerebellum ratio (SCr) was
      determined by applying a fixed circular or rectangular striatal and fuzzy
      cerebellar regions. The effect of introducing scatter compensation (Sc) on
      quantification and on SCr was investigated. RESULTS: The regression coefficient
      (Rc) of SCr computed for both systems was close to identity (IRIX=0.999x
      (PRISM)+0.48 and 1.01x(PRISM)+0.86 for right and left striatum). Rc of SCr values
      in the phantom studies was closer to identity when Sc was added (IRIX=0.982x
      [PRISM]+0.724 with Sc vs 1.22x[PRISM]-0.32 without Sc). SCr values were higher
      for IRIX by 5-10%. Including Sc increased the percent recovery and the linear
      dynamic range for both systems; however, fan beam recovery decreased at low SCr
      values. The delineation of the striatal boundaries improved after applying Sc.
      Identifying the cerebellar region was easier with PRISM owing to significantly
      higher count statistics. Both systems performed equally well with respect to
      image quality. Visual scoring by 2 observers correlated significantly on the k
      test (K: 0.883, T: 10, P<0.0001). CONCLUSION: A simple linear correction is
      applicable to ''normal'' reference data set to migrate from one system to
      another; however, data acquisition and quantification parameters need to be
      standardized. Higher recovery values are dependent on system resolution. The
      spatial distribution and image quality of DaTSCAN on different high-resolution
      systems applying standardized acquisition and reconstruction protocols is less
      operator dependent and does not affect visual rating of striatal DaT loss.

PMID- 17220823
TI  - Near work, education, family history, and myopia in Greek conscripts.
AB  - AIMS: To investigate potential factors associated with the presence of myopia in
      a cohort of young adult men carrying out their military service in Greece.
      METHODS: A nested case-control study of 200 conscripts (99 myopes and 101 non
      myopes). The cohort consisted of approximately 1000 conscripts in compulsory
      national service. All cohort members had been screened for refractive errors by
      Snellen visual acuity measurement at presentation to military service;
      individuals not achieving visual activity 6/6 underwent noncycloplaegic
      refraction. The study sample consisted of the first 99 myopic and 101 nonmyopic
      conscripts who attended the study. In-person interviews of these 200 conscripts
      were conducted to obtain information on family history, occupation, level of
      education, near-work activities, and sleeping behaviour. chi(2) and Mann-Whitney
      tests were used as univariate analysis methods to identify the potential factors
      associated with the presence of myopia. Multiple logistic regression was used to
      estimate the adjusted relative risk of myopia. RESULTS: Univariate analysis
      showed that parental family history (P<0.001), older age (P<0.001), tertiary
      education (P<0.001), hours of reading per day (P<0.001), hours of computer use
      per day (P<0.001), and higher social classes (P<0.001) were associated with
      myopia. Sleeping in artificial or ambient light was not associated with myopia
      (P=0.75). Multiple logistic regression analysis showed that older age (OR=1.25,
      95% CI 1.05-1.49), tertiary education (OR=12.67, 95% CI 3.57-44.88) and parental
      family history (OR=3.39, 95% CI 1.56-7.36) were independently associated with
      myopia. CONCLUSION: In young Greek conscripts, parental family history, older
      age, and education level are independently associated with myopia.

PMID- 17220824
TI  - Lack of benefit of early awareness to age-related macular degeneration.
AB  - AIMS: To assess the rate of early awareness to the presence of age-related
      macular degeneration (AMD) and whether it enables early detection of transition
      to neovascular AMD (NVAMD) as compared with patients whose first presentation to
      an ophthalmologist is already at the neovascular stage of disease. METHODS: A
      retrospective analysis of 268 eyes of 268 consecutive patients with newly
      diagnosed NVAMD that were treated in a tertiary referral centre was performed.
      Patients were classified into those who were unaware (Group 1), or aware (Group
      2), of the fact that they had AMD before diagnosis of NVAMD. Visual acuity,
      lesion size and composition, and demographics were compared between both groups.
      RESULTS: In all, 185 patients (69%) and 83 patients (31%) were classified to
      Groups 1 and 2, respectively. Patients in Groups 1 and 2 had similar demographic
      characteristics, presenting visual acuity and lesion size, and lesion
      compositions. Group 1 patients were more likely to have a positive history for
      smoking (41 vs26% in Group 2, P=0.03), whereas Group 2 patients were more likely
      to have positive family history for AMD (20 vs10%, P=0.02). CONCLUSIONS: These
      data suggest that current screening methods fail to identify the majority of
      patients with AMD before the development of NVAMD. The findings also demonstrate
      that in the routine clinical setting, prior awareness of AMD may not facilitate
      early detection of treatable choroidal neovascularization lesions.

PMID- 17220825
TI  - Steroid-induced ptosis: case studies and histopathologic analysis.
AB  - PURPOSE: The purpose of this study was to review patients who developed ptosis
      after subtenon's steroid injection and to study the mechanism of steroid-induced
      ptosis in an animal model. METHODS: Part 1. Twenty-two patients with uveitis who
      had received posterior subtenon's triamcinolone acetonide injections were
      retrospectively reviewed. Demographics, type of uveitis, type and number of
      surgeries, pre and postoperative marginal reflex distance (MRD1), and clinical
      outcomes were evaluated. Part 2. Study of rabbit levator muscle and aponeurosis
      histopathology after subtenon's triamcinolone injection was performed. RESULTS:
      Part 1. The average age was 44.6 years (range: 14-85 years) with a mean follow-up
      of 14 months. The most common causes of uveitis included uveitis after cataract
      extraction (five), pars planitis (three), multifocal choroiditis (three), and
      juvenile rheumatoid arthritis (three). The average time to documented onset of
      ptosis was 13.9 months (range: 0-49 months). In patients who received only one
      steroid injection, the average time to ptosis recorded was 2.7 months (range: 0-6
      months). Seventeen patients underwent ptosis repair. Part 2. No ptosis was noted
      in the experimental and control groups. Histopathologic analysis of levator
      tissues revealed no significant difference in atrophy or degree of inflammation
      between experimental and control groups. CONCLUSIONS: Ptosis following subtenon's
      steroid injection ranged from mild to moderate and occurred a few months after
      steroid injection. Prior studies of muscles and periocular tissues exposed to
      corticosteroids demonstrated degenerative muscle changes; our studies revealed no
      histopathologic changes in the levator muscle or aponeurosis.

PMID- 17220826
TI  - Effect of immersion disinfection with Perform-ID on alginate, an alginate
      alternative, an addition-cured silicone and resultant type III gypsum casts.
AB  - OBJECTIVE: This study investigated the effect of a commonly used immersion
      disinfectant upon three different impression materials and any subsequent effects
      on the abrasion resistance, hardness and surface detail reproduction of gypsum
      casts. DESIGN: A laboratory study. MATERIALS AND METHODS: Under standardised
      conditions a total of 120 impressions were made of a ruled test block using
      irreversible hydrocolloid (Alginoplast), an 'alginate alternative' addition-cure
      silicone (Position Penta) and a conventional addition-cure silicone (President).
      The impressions were examined for surface detail reproduction prior to and after
      disinfection with Perform-ID. The type III casts were evaluated for surface
      detail reproduction, surface hardness and abrasion resistance. RESULTS: (1) None
      of the disinfected alginate specimens could reproduce the 50 microm line. (2)
      Casts produced from the disinfected alginate were significantly less hard than
      from disinfected Position Penta and President (P <0.001). (3) Disinfection
      significantly affected the abrasion resistance of casts made from Position Penta
      (P = 0.029). (4) Disinfection did not significantly affect President or its
      subsequent casts (P >0.05). CONCLUSION: If disinfecting with Perform-ID, the
      impression should be made with a conventional addition-cured silicone if good
      surface detail reproduction of the impression material and a hard and abrasion
      resistant type III gypsum cast are required.

PMID- 17220827
TI  - TMD and occlusion part I. Damned if we do? Occlusion: the interface of dentistry
      and orthodontics.
AB  - OBJECTIVES: To review how occlusion, facial growth, TM disc position and
      malocclusion may relate to TMD; to review clinical studies investigating TMD pre-
      and post-orthodontic treatment as well as other studies linking occlusal features
      with TMD highlighting their limitations; and to make suggestions for improved
      study designs in the future in order to provide an evidence-base for clinical
      practice. DESIGN: Review article. METHODS: Electronic databases (MEDLINE and the
      Cochrane Database of Systematic Reviews) were used to select relevant and
      frequently cited studies (mean: 28 citations). Citation rate was confirmed using
      the Web of Science. Study designs are reviewed and weaknesses discussed. RESULTS:
      Evidence is lacking to suggest static occlusal factors cause TMD. CONCLUSIONS:
      Poor study designs have led to much of the controversy over whether occlusal
      factors (including orthodontics) 'cause' TMD. In order to provide an evidence
      base for future clinical practice, suggestions to improve study designs are made.

PMID- 17220828
TI  - TMD and occlusion part II. Damned if we don't? Functional occlusal problems: TMD
      epidemiology in a wider context.
AB  - OBJECTIVES: To review studies investigating how functional occlusion may relate
      to TMD and how bruxism may relate to TMD; to review the epidemiology of TMD and
      relate this to the context of clinical occlusal studies and other aetiological
      factors. Deficiencies in study design are highlighted and suggestions made to
      improve future study designs in order to provide an evidence-base for clinical
      practice. DESIGN: Review article. METHODS: Electronic databases (MEDLINE and the
      Cochrane Database of Systematic Reviews) were used to select relevant and
      frequently cited studies (mean: 40 citations). Citation rate was confirmed using
      the Web of Science. Study designs are reviewed and weaknesses and implications
      discussed. RESULTS: Evidence is lacking to suggest functional occlusal factors
      cause TMD. Investigation of other aetiological factors has been relatively
      neglected. CONCLUSIONS: Neither static nor dynamic occlusal factors (including
      orthodontics) can be said to 'cause' TMD. However, other potential aetiological
      factors exist which would benefit from more investigation. This, together with
      improved study designs, would help provide a stronger evidence-base for clinical
      practice in the future.

PMID- 17220829
TI  - Verifiable CPD paper: factors that influence the dental attendance pattern and
      maintenance of oral health for people with multiple sclerosis.
AB  - OBJECTIVE: To determine the impact of multiple sclerosis (MS) on patient
      attendance at dental practices and maintenance of oral health. DESIGN: A cross
      sectional postal questionnaire-based study. SETTING: Leicestershire, United
      Kingdom. SUBJECTS AND METHODS: People with MS in Leicestershire identified from
      local health authority records (n = 476). MAIN OUTCOME MEASURES: Number
      registered at dental practice, frequency of attendance, issues and perspectives
      relating to attendance and maintenance of oral health. RESULTS: A response rate
      of 61% (n = 289) was obtained. When compared to the general population, a higher
      number of people with MS were registered with a dentist (49%:88%) and displayed
      more frequent practice attendance (71%:81%) in the past year. People with MS
      reported difficulties in attending a dentist and maintaining oral health, which
      were exacerbated by deterioration in general health. Problems relating to reduced
      personal mobility had the greatest impact on attendance. CONCLUSIONS: MS has a
      negative impact on perceived patient attendance and maintenance of oral health.
      Patients with a progressive disability could benefit greatly from the provision
      of preventive oral health care. The importance of seeking care earlier rather
      than later needs to be emphasised to both professionals and patients alike.
      Further efforts are required to increase awareness of the importance of oral
      health to the quality of life of people with MS and ensure that individuals with
      physical disabilities receive the same access to dental services as the able
      bodied.

PMID- 17220830
TI  - Dental education--where it needs to be. Dentistry for the community.

PMID- 17220831
TI  - Review the evidence.

PMID- 17220832
TI  - Dental patients in A&E.

PMID- 17220833
TI  - Fear and anxiety.

PMID- 17220834
TI  - Change the policy.

PMID- 17220835
TI  - Welcoming discussion.

PMID- 17220836
TI  - An arcane policy.

PMID- 17220847
TI  - An interdisciplinary approach to treatment planning in implant dentistry.
AB  - The practice of implant dentistry requires an interdisciplinary approach that
      integrates the knowledge, skills and experience of all the disciplines of
      dentistry into a comprehensive treatment plan. This article outlines a
      comprehensive interdisciplinary treatment philosophy designed for developing the
      foundation of optimal aesthetics in implant dentistry. Cases are presented to
      illustrate the utility of interdisciplinary treatment in which specialists are
      recruited to enhance and improve a patient's dental function and aesthetics.

PMID- 17220848
TI  - Verifiable CPD paper: introduction, history of lasers and laser light production.
AB  - The word laser conjures in the mind's eye many aspects of what might be described
      as 'modern' life. The words 'powerful', 'precise' and 'innovative' complement our
      conception of the world in terms of technology, whereas patients often associate
      the words 'magical' and 'lightening quick' with the use of lasers in medical
      practice. The purpose of this series of articles is to explore the history and
      development of lasers, the integration of lasers into clinical dentistry and the
      safeguards as to their regulated use.

PMID- 17220849
TI  - Upper lip blanching and diplopia associated with local anaesthesia of the
      inferior alveolar nerve.
AB  - A case of transient left lateral rectus nerve palsy, following an inferior
      alveolar nerve block to enable the surgical removal of a permanent mandibular
      left third molar tooth, is reported. The anatomy related to this case is
      considered together with suggestions for management of such patients.

PMID- 17220873
TI  - Structural biology: pass the protein.

PMID- 17220874
TI  - Foxp3-dependent programme of regulatory T-cell differentiation.
AB  - Regulatory CD4+ T cells (Tr cells), the development of which is critically
      dependent on X-linked transcription factor Foxp3 (forkhead box P3), prevent self
      destructive immune responses. Despite its important role, molecular and
      functional features conferred by Foxp3 to Tr precursor cells remain unknown. It
      has been suggested that Foxp3 expression is required for both survival of Tr
      precursors as well as their inability to produce interleukin (IL)-2 and
      independently proliferate after T-cell-receptor engagement, raising the
      possibility that such 'anergy' and Tr suppressive capacity are intimately linked.
      Here we show, by dissociating Foxp3-dependent features from those induced by the
      signals preceding and promoting its expression in mice, that the latter signals
      include several functional and transcriptional hallmarks of Tr cells. Although
      its function is required for Tr cell suppressor activity, Foxp3 to a large extent
      amplifies and fixes pre-established molecular features of Tr cells, including
      anergy and dependence on paracrine IL-2. Furthermore, Foxp3 solidifies Tr cell
      lineage stability through modification of cell surface and signalling molecules,
      resulting in adaptation to the signals required to induce and maintain Tr cells.
      This adaptation includes Foxp3-dependent repression of cyclic nucleotide
      phosphodiesterase 3B, affecting genes responsible for Tr cell homeostasis.

PMID- 17220876
TI  - Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3
      expression.
AB  - The naturally occurring regulatory T cell (T(r)) is the pivotal cell type that
      maintains self-tolerance and exerts active immune suppression. The development
      and function of T(r) cells is controlled by Foxp3 (refs 1, 2), a lack of which
      results in loss of T(r) cells and massive multi-organ autoimmunity in scurfy mice
      and IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked)
      patients. It is generally thought that, through a binary mechanism, Foxp3
      expression serves as an on-and-off switch to regulate positively the physiology
      of T(r) cells; however, emerging evidence associates decreased Foxp3 expression
      in T(r) cells with various immune disorders. We hypothesized that Foxp3 regulates
      T(r) cell development and function in a dose-dependent, non-binary manner, and
      that decreased Foxp3 expression can cause immune disease. Here, by generating a
      mouse model in which endogenous Foxp3 gene expression is attenuated in T(r)
      cells, we show that decreased Foxp3 expression results in the development of an
      aggressive autoimmune syndrome similar to that of scurfy mice, but does not
      affect thymic development, homeostatic expansion/maintenance or transforming
      growth-factor-beta-induced de novo generation of Foxp3-expressing cells. The
      immune-suppressive activities of T cells with attenuated Foxp3 expression were
      nearly abolished in vitro and in vivo, whereas their anergic properties in vitro
      were maintained. This was accompanied by decreased expression of T(r) cell
      'signature genes'. Notably, T cells expressing decreased Foxp3 preferentially
      became T-helper 2 (T(h)2)-type effectors even in a T(h)1-polarizing environment.
      These cells instructed T(h)2 differentiation of conventional T cells, which
      contributed to the immune diseases observed in these mice. Thus, decreased Foxp3
      expression causes immune disease by subverting the suppressive function of T(r)
      cells and converting T(r) cells into effector cells; these findings are important
      for understanding the regulation of T(r) cell function and the aetiology of
      various human immune diseases.

PMID- 17220875
TI  - Basis for a ubiquitin-like protein thioester switch toggling E1-E2 affinity.
AB  - Ubiquitin-like proteins (UBLs) are conjugated by dynamic E1-E2-E3 enzyme
      cascades. E1 enzymes activate UBLs by catalysing UBL carboxy-terminal
      adenylation, forming a covalent E1 throught UBL thioester intermediate, and
      generating a thioester-linked E2 throught UBL product, which must be released for
      subsequent reactions. Here we report the structural analysis of a trapped UBL
      activation complex for the human NEDD8 pathway, containing NEDD8's heterodimeric
      E1 (APPBP1-UBA3), two NEDD8s (one thioester-linked to E1, one noncovalently
      associated for adenylation), a catalytically inactive E2 (Ubc12), and MgATP. The
      results suggest that a thioester switch toggles E1-E2 affinities. Two E2 binding
      sites depend on NEDD8 being thioester-linked to E1. One is unmasked by a striking
      E1 conformational change. The other comes directly from the thioester-bound
      NEDD8. After NEDD8 transfer to E2, reversion to an alternate E1 conformation
      would facilitate release of the E2 throught NEDD8 thioester product. Thus,
      transferring the UBL's thioester linkage between successive conjugation enzymes
      can induce conformational changes and alter interaction networks to drive
      consecutive steps in UBL cascades.

PMID- 17220877
TI  - Complementation of placental defects and embryonic lethality by trophoblast
      specific lentiviral gene transfer.
AB  - Placental dysfunction underlies many complications during pregnancy, and better
      understanding of gene function during placentation could have considerable
      clinical relevance. However, the lack of a facile method for placenta-specific
      gene manipulation has hampered investigation of placental organogenesis and the
      treatment of placental dysfunction. We showed previously that transduction of
      fertilized mouse eggs with lentiviral vectors leads to transgene expression in
      both the fetus and the placenta. Here we report placenta-specific gene
      incorporation by lentiviral transduction of mouse blastocysts after removal of
      the zona pellucida. All of the placentas analyzed, but none of the fetuses, were
      transgenic. Application of this method substantially rescued mice deficient in
      Ets2, Mapk14 (also known as p38alpha) and Mapk1 (also known as Erk2) from
      embryonic lethality caused by placental defects. Ectopic expression of Mapk11
      also complemented Mapk14 deficiency during placentation.

PMID- 17220878
TI  - High-throughput mapping of the chromatin structure of human promoters.
AB  - Our understanding of how chromatin structure influences cellular processes such
      as transcription and replication has been limited by a lack of nucleosome
      positioning data in human cells. We describe a high-resolution microarray
      approach combined with an analysis algorithm to examine nucleosome positioning in
      3,692 promoters within seven human cell lines. Unlike unexpressed genes without
      transcription-preinitiation complexes at their promoters, expressed genes or
      genes containing preinitiation complexes exhibit characteristic nucleosome-free
      regions at their transcription start sites. The combination of these nucleosome
      data with chromatin immunoprecipitation-chip analyses reveals that the melanocyte
      master regulator microphthalmia-associated transcription factor (MITF)
      predominantly binds nucleosome-free regions, supporting the model that
      nucleosomes limit sequence accessibility. This study presents a global view of
      human nucleosome positioning and provides a high-throughput tool for analyzing
      chromatin structure in development and disease.

PMID- 17220879
TI  - Chemotaxis in shallow gradients is mediated independently of PtdIns 3-kinase by
      biased choices between random protrusions.
AB  - Current models of eukaryotic chemotaxis propose that directional sensing causes
      localized generation of new pseudopods. However, quantitative analysis of
      pseudopod generation suggests a fundamentally different mechanism for chemotaxis
      in shallow gradients: first, pseudopods in multiple cell types are usually
      generated when existing ones bifurcate and are rarely made de novo; second, in
      Dictyostelium cells in shallow chemoattractant gradients, pseudopods are made at
      the same rate whether cells are moving up or down gradients. The location and
      direction of new pseudopods are random within the range allowed by bifurcation
      and are not oriented by chemoattractants. Thus, pseudopod generation is
      controlled independently of chemotactic signalling. Third, directional sensing is
      mediated by maintaining the most accurate existing pseudopod, rather than through
      the generation of new ones. Finally, the phosphatidylinositol 3-kinase (PI(3)K)
      inhibitor LY294002 affects the frequency of pseudopod generation, but not the
      accuracy of selection, suggesting that PI(3)K regulates the underlying mechanism
      of cell movement, rather than control of direction.

PMID- 17220880
TI  - Interaction between beta-catenin and HIF-1 promotes cellular adaptation to
      hypoxia.
AB  - Aberrant activation of beta-catenin promotes cell proliferation and initiates
      colorectal tumorigenesis. However, the expansion of tumours and the inadequacy of
      their local vasculature results in areas of hypoxia where cell growth is
      typically constrained. Here, we report a novel diversion in beta-catenin
      signalling triggered by hypoxia. We show that hypoxia inhibits beta-catenin-T
      cell factor-4 (TCF-4) complex formation and transcriptional activity, resulting
      in a G1 arrest that involves the c-Myc-p21 axis. Additionally, we find that
      hypoxia inducible factor-1alpha (HIF-1alpha) competes with TCF-4 for direct
      binding to beta-catenin. DNA-protein interaction studies reveal that beta-catenin
      HIF-1alpha interaction occurs at the promoter region of HIF-1 target genes.
      Furthermore, rigorous analyses indicate that beta-catenin can enhance HIF-1
      mediated transcription, thereby promoting cell survival and adaptation to
      hypoxia. These findings demonstrate a dynamic role for beta-catenin in colorectal
      tumorigenesis, where a functional switch is instigated to meet the ever-changing
      needs of the tumour. This study highlights the importance of the microenvironment
      in transcriptional regulation.

PMID- 17220881
TI  - Cortical microtubule arrays undergo rotary movements in Arabidopsis hypocotyl
      epidermal cells.
AB  - Plant-cell expansion is controlled by cellulose microfibrils in the wall with
      microtubules providing tracks for cellulose synthesizing enzymes. Microtubules
      can be reoriented experimentally and are hypothesized to reorient cyclically in
      aerial organs, but the mechanism is unclear. Here, Arabidopsis hypocotyl
      microtubules were labelled with AtEB1a-GFP (Arabidopsis microtubule end-binding
      protein 1a) or GFP-TUA6 (Arabidopsis alpha-tubulin 6) to record long cycles of
      reorientation. This revealed microtubules undergoing previously unseen clockwise
      or counter-clockwise rotations. Existing models emphasize selective shrinkage and
      regrowth or the outcome of individual microtubule encounters to explain
      realignment. Our higher-order view emphasizes microtubule group behaviour over
      time. Successive microtubules move in the same direction along self-sustaining
      tracks. Significantly, the tracks themselves migrate, always in the direction of
      the individual fast-growing ends, but twentyfold slower. Spontaneous sorting of
      tracks into groups with common polarities generates a mosaic of domains. Domains
      slowly migrate around the cell in skewed paths, generating rotations whose
      progressive nature is interrupted when one domain is displaced by collision with
      another. Rotary movements could explain how the angle of cellulose microfibrils
      can change from layer to layer in the polylamellate cell wall.

PMID- 17220882
TI  - Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and
      axonal microtubules.
AB  - To understand the functions of NIPA1, mutated in the neurodegenerative disease
      hereditary spastic paraplegia, and of ichthyin, mutated in autosomal recessive
      congenital ichthyosis, we have studied their Drosophila melanogaster ortholog,
      spichthyin (Spict). Spict is found on early endosomes. Loss of Spict leads to
      upregulation of bone morphogenetic protein (BMP) signaling and expansion of the
      neuromuscular junction. BMP signaling is also necessary for a normal microtubule
      cytoskeleton and axonal transport; analysis of loss- and gain-of-function
      phenotypes indicate that Spict may antagonize this function of BMP signaling.
      Spict interacts with BMP receptors and promotes their internalization from the
      plasma membrane, implying that it inhibits BMP signaling by regulating BMP
      receptor traffic. This is the first demonstration of a role for a hereditary
      spastic paraplegia protein or ichthyin family member in a specific signaling
      pathway, and implies disease mechanisms for hereditary spastic paraplegia that
      involve dependence of the microtubule cytoskeleton on BMP signaling.

PMID- 17220883
TI  - Presynaptic Ca2+ buffers control the strength of a fast post-tetanic
      hyperpolarization mediated by the alpha3 Na(+)/K(+)-ATPase.
AB  - The excitability of CNS presynaptic terminals after a tetanic burst of action
      potentials is important for synaptic plasticity. The mechanisms that regulate
      excitability, however, are not well understood. Using direct recordings from the
      rat calyx of Held terminal, we found that a fast Na(+)/K(+)-ATPase (NKA)-mediated
      post-tetanic hyperpolarization (PTH) controls the probability and precision of
      subsequent firing. Notably, increasing the concentration of internal Ca(2+)
      buffers or decreasing Ca(2+) influx led to larger PTH amplitudes, indicating that
      an increase in [Ca(2+)](i) regulates PTH via inhibition of NKAs. The
      characterization for the first time of a presynaptic NKA pump current, combined
      with immunofluorescence staining, identified the alpha3-NKA isoform on calyx
      terminals. Accordingly, the increased ability of the calyx to faithfully fire
      during a high-frequency train as it matures is paralleled by a larger expression
      of alpha3-NKA during development. We propose that this newly discovered Ca(2+)
      dependence of PTH is important in the post-burst excitability of nerve terminals.

PMID- 17220884
TI  - Notch signal organizes the Drosophila olfactory circuitry by diversifying the
      sensory neuronal lineages.
AB  - An essential feature of the organization and function of the vertebrate and
      insect olfactory systems is the generation of a variety of olfactory receptor
      neurons (ORNs) that have different specificities in regard to both odorant
      receptor expression and axonal targeting. Yet the underlying mechanisms that
      generate this neuronal diversity remain elusive. Here we demonstrate that the
      Notch signal is involved in the diversification of ORNs in Drosophila
      melanogaster. A systematic clonal analysis showed that a cluster of ORNs housed
      in each sensillum were differentiated into two classes, depending on the level of
      Notch activity in their sibling precursors. Notably, ORNs of different classes
      segregated their axonal projections into distinct domains in the antennal lobes.
      In addition, both the odorant receptor expression and the axonal targeting of
      ORNs were specified according to their Notch-mediated identities. Thus, Notch
      signaling contributes to the diversification of ORNs, thereby regulating multiple
      developmental events that establish the olfactory map in Drosophila.

PMID- 17220885
TI  - Synaptic vesicles recycling spontaneously and during activity belong to the same
      vesicle pool.
AB  - Recently, it has been claimed that vesicles recycling spontaneously and during
      activity belong to different pools. Here we simultaneously measured, using
      spectrally separable styryl dyes, the release kinetics of vesicles recycled
      spontaneously or upon stimulation and the effects of the v-ATPase blocker
      folimycin on the frequency of miniature postsynaptic currents in rat hippocampal
      neurons. Our results provide evidence as to the identities of the vesicle pools
      recycling at rest and during stimulation.

PMID- 17220886
TI  - Hippocampal cellular and network activity in freely moving echolocating bats.
AB  - The hippocampus is crucial for episodic and spatial memory. In freely moving
      rodents, hippocampal pyramidal neurons show spatially selective firing when the
      animal passes through a neuron's 'place-field', and theta-band oscillation is
      continuously present during locomotion. Here we report the first hippocampal
      recordings from echolocating bats, mammals phylogenetically distant from rodents,
      which showed place cells very similar to those of rodents. High-frequency
      'ripple' oscillations were also rodent-like. Theta oscillation, however, differed
      from rodents in two important ways: (i) theta occurred when bats explored the
      environment without locomoting, using distal sensing through echolocation, and
      (ii) theta was not continuous, but occurred in short intermittent bouts. The
      intermittence of theta suggests that models of hippocampal function that rely on
      continuous theta may not apply to bats. Our data support the hypothesis that
      theta oscillation in the mammalian hippocampus is involved in sequence learning
      and hence, theta power should increase with sensory-input rate-which explains why
      theta power correlates with running speed in rodents and with echolocation call
      rate in bats.

PMID- 17220887
TI  - Sharpened cochlear tuning in a mouse with a genetically modified tectorial
      membrane.
AB  - Frequency tuning in the cochlea is determined by the passive mechanical
      properties of the basilar membrane and active feedback from the outer hair cells,
      sensory-effector cells that detect and amplify sound-induced basilar membrane
      motions. The sensory hair bundles of the outer hair cells are imbedded in the
      tectorial membrane, a sheet of extracellular matrix that overlies the cochlea's
      sensory epithelium. The tectorial membrane contains radially organized collagen
      fibrils that are imbedded in an unusual striated-sheet matrix formed by two
      glycoproteins, alpha-tectorin (Tecta) and beta-tectorin (Tectb). In Tectb(-/-)
      mice the structure of the striated-sheet matrix is disrupted. Although these mice
      have a low-frequency hearing loss, basilar-membrane and neural tuning are both
      significantly enhanced in the high-frequency regions of the cochlea, with little
      loss in sensitivity. These findings can be attributed to a reduction in the
      acting mass of the tectorial membrane and reveal a new function for this
      structure in controlling interactions along the cochlea.

PMID- 17220888
TI  - A multistep epigenetic switch enables the stable inheritance of DNA methylation
      states.
AB  - In many prokaryotes and eukaryotes, DNA methylation at cis-regulatory sequences
      determines whether gene expression is on or off. Stable inheritance of these
      expression states is required in bacterial pathogenesis, cancer and developmental
      pathways. Here we delineate the factors that control the stability of these
      states by using the agn43 gene in Escherichia coli as a model system. Systematic
      disruption of this system shows that a functional switch requires the presence of
      several, rarely occupied, intermediate states that separate the 'on' and 'off'
      states. Cells that leave the on and off state enter different intermediate
      states, where there is a strong bias that drives cells back to their original
      state. The intermediate states therefore act as buffers that prevent back and
      forth switching. This mechanism of generating multiple states is an alternative
      to feedback regulation, and its general principle should be applicable to the
      analysis of other epigenetic switches and the design of synthetic circuits.

PMID- 17220889
TI  - Zebrafish miR-214 modulates Hedgehog signaling to specify muscle cell fate.
AB  - Numerous microRNAs (miRNAs) have been discovered in the genomes of higher
      eukaryotes, and functional studies indicate that they are important during
      development. However, little is known concerning the function of individual
      miRNAs. We approached this problem in zebrafish by combining identification of
      miRNA expression, functional analyses and experimental validation of potential
      targets. We show that miR-214 is expressed during early segmentation stages in
      somites and that varying its expression alters the expression of genes regulated
      by Hedgehog signaling. Inhibition of miR-214 results in a reduction or loss of
      slow-muscle cell types. We show that su(fu) mRNA, encoding a negative regulator
      of Hedgehog signaling, is targeted by miR-214. Through regulation of su(fu), miR
      214 enables precise specification of muscle cell types by sharpening cellular
      responses to Hedgehog.

PMID- 17220890
TI  - The neuronal sortilin-related receptor SORL1 is genetically associated with
      Alzheimer disease.
AB  - The recycling of the amyloid precursor protein (APP) from the cell surface via
      the endocytic pathways plays a key role in the generation of amyloid beta peptide
      (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1
      neuronal sorting receptor are associated with late-onset Alzheimer disease. These
      variants, which occur in at least two different clusters of intronic sequences
      within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific
      expression of SORL1. We also show that SORL1 directs trafficking of APP into
      recycling pathways and that when SORL1 is underexpressed, APP is sorted into
      Abeta-generating compartments. These data suggest that inherited or acquired
      changes in SORL1 expression or function are mechanistically involved in causing
      Alzheimer disease.

PMID- 17220891
TI  - The quantitative trait gene latexin influences the size of the hematopoietic stem
      cell population in mice.
AB  - We mapped quantitative trait loci that accounted for the variation in
      hematopoietic stem cell (HSC) numbers between young adult C57BL/6 (B6) and DBA/2
      (D2) mice. In reciprocal chromosome 3 congenic mice, introgressed D2 alleles
      increased HSC numbers owing to enhanced proliferation and self-renewal and
      reduced apoptosis, whereas B6 alleles had the opposite effects. Using
      oligonucleotide arrays, real-time PCR and protein blots, we identified latexin
      (Lxn), a gene whose differential transcription and expression was associated with
      the allelic differences. Expression was inversely correlated with the number of
      HSCs; therefore, ectopic expression of Lxn using a retroviral vector decreased
      stem cell population size. We identified clusters of SNPs upstream of the Lxn
      transcriptional start site, at least two of which are associated with potential
      binding sites for transcription factors regulating stem cells. Thus, promoter
      polymorphisms between the B6 and D2 alleles may affect Lxn gene expression and
      consequently influence the population size of hematopoietic stem cells.

PMID- 17220892
TI  - Maintenance of the Foxp3-dependent developmental program in mature regulatory T
      cells requires continued expression of Foxp3.
AB  - The transcription factor Foxp3 is required for the development of regulatory T
      cells (T(reg) cell). Here we report that induced ablation of a loxP-flanked Foxp3
      allele in mature T(reg) cells resulted in the loss of their suppressive function
      in vivo and acquisition of the ability to produce interleukin 2 and T helper type
      1 cytokines. Furthermore, after adoptive transfer in the absence of functional
      T(reg) cells into lymphopenic hosts, T(reg) cells with deletion of Foxp3
      proliferated and were predominant among tissue-infiltrating T cells. In agreement
      with those results, we found deregulation of Foxp3 target gene expression after
      Foxp3 deletion. Thus, continued Foxp3 expression in mature T(reg) cells is needed
      to maintain the transcriptional and functional program established during T(reg)
      cell development.

PMID- 17220893
TI  - Small-molecule mimics of an alpha-helix for efficient transport of proteins into
      cells.
AB  - We designed and synthesized small-molecule mimics of an alpha-helical peptide
      protein transduction domain (PTD). These small-molecule carriers, which we termed
      SMoCs, are easily coupled to biomolecules, and efficiently deliver dye molecules
      and recombinant proteins into a variety of cell types. We designed the SMoCs
      using molecular modeling techniques. As an example of a protein cargo, we applied
      this new technology to the internalization of the DNA replication licensing
      repressor geminin, in vitro, providing evidence that extracellularly delivered
      SMoC-geminin can have an antiproliferative effect on human cancer cells. Uptake
      of SMoC-geminin was inhibited at 4 degrees C and by chlorpromazine, a compound
      that induces misassembly of clathrin-coated pits at the cell surface. Thus the
      mechanism of uptake is likely to be clathrin-mediated endocytosis.

PMID- 17220894
TI  - Transposon-tagged mutagenesis in the rat.
AB  - Although the laboratory rat (Rattus norvegicus) is an indispensable experimental
      animal for biomedical research and drug development, the lack of embryonic stem
      cell lines hampers gene-knockout studies. Here we report the successful
      generation of insertional mutant rats using the Sleeping Beauty (SB) transposon
      system. This would benefit a variety of biomedical research fields for which the
      rat model is better suited than the mouse model.

PMID- 17220895
TI  - The guanylate kinase domain of the MAGUK PSD-95 binds dynamically to a conserved
      motif in MAP1a.
AB  - The postsynaptic density protein PSD-95 and related membrane-associated guanylate
      kinases are scaffolding proteins, whose modular interaction motifs organize
      protein complexes at cell junctions. The signature guanylate kinase domain (GK)
      contains elements of the protein's GMP-binding site but does not bind nucleotide.
      Instead, the GK domain has evolved from an enzyme to a protein-protein
      interaction motif. Here, we show that this canonical GMP-binding region interacts
      with microtubule-associated protein-1a (MAP1a) and we present a structural model.
      We determine the consensus GK-binding sequence in MAP1a and demonstrate that PSD
      95 can use a similar interaction mode to bind diverse protein partners.
      Furthermore, we show that PSD-95 GK has adopted the conformational flexibility of
      the ancestral enzyme to bind its varied ligands, which suggests a mechanism of
      regulation.

PMID- 17220896
TI  - A general amphipathic alpha-helical motif for sensing membrane curvature.
AB  - The Golgi-associated protein ArfGAP1 has an unusual membrane-adsorbing
      amphipathic alpha-helix: its polar face is weakly charged, containing mainly
      serine and threonine residues. We show that this feature explains the specificity
      of ArfGAP1 for curved versus flat lipid membranes. We built an algorithm to
      identify other potential amphipathic alpha-helices rich in serine and threonine
      residues in protein databases. Among the identified sequences, we show that three
      act as membrane curvature sensors. In the golgin GMAP-210, the sensor may serve
      to trap small vesicles at the end of a long coiled coil. In Osh4p/Kes1p, which
      transports sterol between membranes, the sensor controls access to the sterol
      binding pocket. In the nucleoporin Nup133, the sensor corresponds to an exposed
      loop of a beta-propeller structure. Ser/Thr-rich amphipathic helices thus define
      a general motif used by proteins of various functions for sensing membrane
      curvature.

PMID- 17220897
TI  - Crystal structure of a complete ternary complex of TCR, superantigen and peptide
      MHC.
AB  - 'Superantigens' (SAgs) trigger the massive activation of T cells by simultaneous
      interactions with MHC and TCR receptors, leading to human diseases. Here we
      present the first crystal structure, at 2.5-A resolution, of a complete ternary
      complex between a SAg and its two receptors, HLA-DR1/HA and TCR. The most
      striking finding is that the SAg Mycoplasma arthritidis mitogen, unlike others,
      has direct contacts not only with TCR Vbeta but with TCR Valpha.

PMID- 17220898
TI  - A topological mechanism for TRF2-enhanced strand invasion.
AB  - Telomeres can fold into t-loops that may result from the invasion of the 3'
      overhang into duplex DNA. Their formation is facilitated in vitro by the
      telomeric protein TRF2, but very little is known regarding the mechanisms
      involved. Here we reveal that TRF2 generates positive supercoiling and condenses
      DNA. Using a variety of TRF2 mutants, we demonstrate a strong correlation between
      this topological activity and the ability to stimulate strand invasion. We also
      report that these properties require the combination of the TRF-homology (TRFH)
      domain of TRF2 with either its N- or C-terminal DNA-binding domains. We propose
      that TRF2 complexes, by constraining DNA around themselves in a right-handed
      conformation, can induce untwisting of the neighboring DNA, thereby favoring
      strand invasion. Implications of this topological model in t-loop formation and
      telomere homeostasis are discussed.

PMID- 17220899
TI  - Adenovirus type 11 binding alters the conformation of its receptor CD46.
AB  - Adenoviruses (Ads) are important human pathogens and valuable gene delivery
      vehicles. We report here the crystal structure of the species B Ad11 knob
      complexed with the Ad11-binding region of its receptor CD46. The conformation of
      bound CD46 differs profoundly from its unbound state, with the bent surface
      structure straightened into an elongated rod. This mechanism of interaction is
      likely to be conserved among many pathogens that target CD46 or related
      molecules.

PMID- 17220900
TI  - Two interconverting Fe(IV) intermediates in aliphatic chlorination by the
      halogenase CytC3.
AB  - Enzymatic incorporation of a halogen atom is a common feature in the biosyntheses
      of more than 4,500 natural products. Halogenation of unactivated carbon centers
      in the biosyntheses of several compounds of nonribosomal peptide origin is
      carried out by a class of mononuclear nonheme iron enzymes that require alpha
      ketoglutarate (alphaKG, 1), chloride and oxygen. To investigate the ability of
      these enzymes to functionalize unactivated methyl groups, we characterized the
      chlorination of the gamma-methyl substituent of L-2-aminobutyric acid (L-Aba, 2)
      attached to the carrier protein CytC2 by iron halogenase (CytC3) from soil
      Streptomyces sp. We identified an intermediate state comprising two high-spin
      Fe(IV) complexes in rapid equilibrium. At least one of the Fe(IV) complexes
      abstracts hydrogen from the substrate. The demonstration that chlorination
      proceeds through an Fe(IV) intermediate that cleaves a C-H bond reveals the
      mechanistic similarity of aliphatic halogenases to the iron- and alphaKG
      dependent hydroxylases.

PMID- 17220901
TI  - Bioinformatic discovery of novel bioactive peptides.
AB  - Short synthetic oligopeptides based on regions of human proteins that encompass
      functional motifs are versatile reagents for understanding protein signaling and
      interactions. They can either mimic or inhibit the parent protein's activity and
      have been used in drug development. Peptide studies typically either derive
      peptides from a single identified protein or (at the other extreme) screen random
      combinatorial peptides, often without knowledge of the signaling pathways
      targeted. Our objective was to determine whether rational bioinformatic design of
      oligopeptides specifically targeted to potentially signaling-rich juxtamembrane
      regions could identify modulators of human platelet function. High-throughput in
      vitro platelet function assays of palmitylated cell-permeable oligopeptides
      corresponding to these regions identified many agonists and antagonists of
      platelet function. Many bioactive peptides were from adhesion molecules,
      including a specific CD226-derived inhibitor of inside-out platelet signaling.
      Systematic screens of this nature are highly efficient tools for discovering
      short signaling motifs in molecular signaling pathways.

PMID- 17220902
TI  - Total body irradiation and granulocyte colony-stimulating factor-combined high
      dose cytarabine as a conditioning regimen in allogeneic hematopoietic stem cell
      transplantation for advanced myelodysplastic syndrome: a single-institute
      experience.
AB  - In this study, we retrospectively evaluated the efficacy and safety of total body
      irradiation (TBI) and granulocyte colony-stimulating factor (G-CSF)-combined high
      dose cytarabine as a conditioning regimen for allogeneic hematopoietic stem cell
      transplantation (HSCT) in patients with advanced myelodysplastic syndrome (MDS).
      We evaluated 22 patients with advanced MDS, including refractory anemia with
      excess blasts (RAEB; n=10), RAEB in transformation (n=2), acute myelogenous
      leukemia transformed from MDS (n=6) and chronic myelomonocytic leukemia (n=4).
      The conditioning regimen consisted of 12 Gy of TBI and high-dose cytarabine (3
      g/m(2)) every 12 h for 4 days, and the cytarabine was combined with continuous
      administration of G-CSF. The stem cell sources were bone marrow or peripheral
      blood stem cells from human leukocyte antigen (HLA)-identical siblings (n=12) and
      bone marrow from HLA serologically matched unrelated donors (n=10). Three
      patients experienced disease relapse, two of whom died of disease progression. Of
      22 patients, 16 are currently alive and disease-free. The 5-year estimated
      overall survival, disease-free survival, relapse and non-relapse mortality rates
      are 76.7, 72.2, 16.6 and 14.1%, respectively. These results suggest that G-CSF
      combined high-dose cytarabine could be a promising component of the conditioning
      regimen of allogeneic HSCT for advanced MDS, providing a low incidence of both
      relapse and treatment-related mortality.

PMID- 17220903
TI  - Toxic epidermal necrolysis after allogeneic haematopoietic stem cell
      transplantation.

PMID- 17220904
TI  - Biochemical monitoring after haemopoietic stem cell transplant for Hurler
      syndrome (MPSIH): implications for functional outcome after transplant in
      metabolic disease.
AB  - Hurler Syndrome is corrected by allogeneic BMT by the action of donor enzyme on
      recipient tissue. In this paper, we describe monitoring of 39 patients
      transplanted in two centres to determine donor chimerism, enzyme level and
      residual substrate - expressed as dermatan sulphate to chondroitin sulphate
      ratio. We show that in fully engrafted recipients, the enzyme level, expressed as
      mumol/g total protein/h, post-transplant is 24.2 from an unrelated donor and 10.2
      from a heterozygote family donor (P<0.0001). There is a tight relationship
      between mean post-transplant enzyme level and residual substrate - Spearman's
      rank correlation coefficient (Rho) was -0.76 and -0.80 at 12 and 24 months,
      respectively (P<0.0001). We propose that these differences affect patient
      outcome. As unrelated donor transplant outcomes improve and especially given the
      higher levels of donor cell engraftment following cord transplants, our data
      might influence donor selection where only heterozygote-matched family members
      are available.

PMID- 17220905
TI  - Fludarabine vs cladribine plus busulfan and low-dose TBI as reduced intensity
      conditioning for allogeneic hematopoietic stem cell transplantation: a
      prospective randomized trial.
AB  - Purine analogs are often used for conditioning preceding allogeneic hematopoietic
      stem cell transplantation (HCT). We prospectively tested fludarabine (Flu) 40
      mg/m(2)/day x 5 days vs cladribine (Clad) 10 mg/m(2)/day x 5 days plus oral
      busulfan (1 mg/kg q6 h x 2 days) and total body irradiation 200 cGy in 32
      recipients of matched sibling and unrelated donor (URD) HCT. Patients were
      similar in age (median 52 years), diagnosis, extensive pre-HCT therapy (56 vs
      63%), and high-risk disease status (81 vs 93%). Neutrophil engraftment was prompt
      (median 11 vs 12 days), but early graft failure using Clad halted randomization.
      Platelet recovery was prompt (median Flu 18 vs Clad 24 days). Graft-versus-host
      disease (GVHD) after Flu vs Clad was similar; (acute grade II/IV 56 vs 69%,
      P=0.26; chronic 50 vs 31%, P=0.27). Nonrelapse mortality (Flu 25 vs Clad 38%,
      P=0.47) and progression-free survival at 3 years were similar as well.
      Multivariate analyses showed slightly, but not significantly lower relative risk
      (RR) of neutrophil engraftment with Clad (RR 0.6 (95% CI 0.2-1.3) P=0.16) and
      with URD RR 0.4 (0.2-1.0) P=0.04). Older patients with advanced hematologic
      malignancies achieve satisfactory outcomes using either of these reduced
      intensity conditioning regimens.

PMID- 17220907
TI  - The synthetic TRH analogue taltirelin exerts modality-specific antinociceptive
      effects via distinct descending monoaminergic systems.
AB  - BACKGROUND AND PURPOSE: Exogenously administered thyrotropin-releasing hormone
      (TRH) is known to exert potent but short-acting centrally-mediated
      antinociceptive effects. We sought to investigate the mechanisms underlying these
      effects using the synthetic TRH analogue taltirelin, focusing on the descending
      monoaminergic systems in mice. EXPERIMENTAL APPROACH: The mice received systemic
      or local injections of taltirelin combined with either central noradrenaline (NA)
      or 5-hydroxytryptamine (5-HT) depletion by 6-hydroxydopamine (6-OHDA) or DL-p
      chlorophenylalanine (PCPA), respectively, or blockade of their receptors. The
      degree of antinociception was determined using the tail flick and tail pressure
      tests. KEY RESULTS: Subcutaneously (s.c.) administered taltirelin exhibited dose
      dependent antinociceptive effects in the tail flick and tail pressure tests.
      These effects appeared to be primarily supraspinally mediated, since
      intracerebroventricularly (i.c.v.) but not intrathecally (i.t.) injected
      taltirelin generated similar effects. Depletion of central NA abolished only the
      analgesic effect of taltirelin (s.c. and i.c.v.) on mechanical nociception. By
      contrast, depletion of central 5-HT abolished only its analgesic effect on
      thermal nociception. Intraperitoneal (i.p.) and i.t. injection of the alpha2
      adrenoceptor antagonist yohimbine respectively reduced the analgesic effect of
      taltirelin (s.c. and i.c.v.) on mechanical nociception. By contrast, the 5-HT1A
      receptor antagonist WAY-100635 (i.p. and i.t.) reduced the effect of taltirelin
      (s.c. and i.c.v.) on thermal nociception. Neither the 5-HT2 receptor antagonist
      ketanserin nor the opioid receptor antagonist naloxone altered the
      antinociceptive effect of taltirelin. CONCLUSIONS AND IMPLICATIONS: These
      findings suggest that taltirelin activates the descending noradrenergic and
      serotonergic pain inhibitory systems, respectively, to exert its analgesic
      effects on mechanical and thermal nociception.

PMID- 17220908
TI  - Long-term treatment with TGFbeta1 impairs mechanotransduction in bovine aortic
      endothelial cells.
AB  - BACKGROUND AND PURPOSE: Vascular endothelial cells play a role in the
      physiological response to mechanical stress. Transforming growth factor beta1
      (TGFbeta1) induces morphological changes in endothelial cells, and this may alter
      their mechanosensitive responses. The aim of this study was to examine the
      effects of TGFbeta1 on hypotonic stress (HTS)-induced responses in bovine aortic
      endothelial cells (BAECs). EXPERIMENTAL APPROACH: Cultured BAECs were treated
      with 3 ng ml(-1) TGFbeta1 for 24 h (24h-TGFbeta1) or 7 days (7d-TGFbeta1).
      Cytosolic actin fibres were stained with rhodamine-phalloidin. Intracellular Ca2+
      concentration was measured using fura2. Tyrosine phosphorylation and RhoA
      expression were assessed by Western blotting. Expression of RhoA mRNA was
      assessed by real-time PCR. KEY RESULTS: BAECs developed pseudopod-like processes
      within 24 h and showed a fibroblast-like appearance after 7 days. HTS induced
      Ca2+ transients via endogenous ATP release in both control and 24h-TGFbeta1 BAECs
      but not in 7d-TGFbeta1 BAECs. We have previously shown that HTS-induced ATP
      release is mediated by sequential activation of RhoA and tyrosine kinases. The
      basal amount of membrane-bound RhoA was significantly lower in 7d-TGFbeta1 than
      in 24h-TGFbeta1 or control BAECs. HTS increased the membrane-bound RhoA to the
      same fractional level in 24h-TGFbeta1 and control BAECs, but its net maximal
      amount was significantly lower in 7d-TGFbeta1. HTS-induced downstream signals of
      RhoA activation, i.e. the tyrosine phosphorylation of FAK and paxillin, were
      markedly suppressed in 7d-TGFbeta1 BAECs. CONCLUSIONS AND IMPLICATIONS: These
      results indicate that long-term treatment with TGFbeta1 does not impair
      mechanoreception in BAECs but impairs mechanotransduction by affecting RhoA
      membrane translocation.

PMID- 17220909
TI  - Involvement of Na+-Ca2+ exchanger in cAMP-mediated relaxation in mice aorta:
      evaluation using transgenic mice.
AB  - BACKGROUND AND PURPOSE: Although vascular smooth muscle cells are known to
      express the Na+-Ca2+ exchanger (NCX), its functional role has remained unclear,
      mainly because of its relatively low expression. We thus investigated the
      involvement of NCX in the mechanism for the forskolin-induced vaso-relaxation,
      using wild type (WT) and transgenic (TG) mice that specifically over-express
      NCX1.3 in smooth muscle. EXPERIMENTAL APPROACH: We examined the relaxing effect
      of forskolin during the pre-contraction induced by 100 nM U46619, a thromboxane
      A2 analogue in the mouse isolated thoracic aorta. We also measured the
      intracellular Ca2+ concentration ([Ca2+]i) in fura-PE3-loaded aortic strips. KEY
      RESULTS: The forskolin-induced decreases in [Ca2+]i and tension were much greater
      in aortas from TG mice than in those from WT mice. In a low Na+ solution,
      forskolin-induced decreases in [Ca2+]i and tension were greatly inhibited in both
      groups of aortas. In WT aortas, the presence of 100 nM SEA0400, an NCX inhibitor,
      had only a little effect on the forskolin-induced decreases in [Ca2+]i, but
      inhibited the forskolin-induced relaxation. However, in TG aortas, the presence
      of SEA0400 greatly inhibited the forskolin-induced decreases in [Ca2+]i and
      tension. CONCLUSIONS AND IMPLICATIONS: The NCX was involved in the forskolin
      induced reduction of [Ca2+]i and tension in the mouse thoracic aorta. Measurement
      of [Ca2+]i and tension in aortas of the TG mouse is thus considered to be a
      useful tool for evaluating the role of NCX in vascular tissue.

PMID- 17220910
TI  - Number of nitrate groups determines reactivity and potency of organic nitrates: a
      proof of concept study in ALDH-2-/- mice.
AB  - BACKGROUND AND PURPOSE: Mitochondrial aldehyde dehydrogenase (ALDH-2) has been
      shown to provide a pathway for bioactivation of organic nitrates and to be prone
      to desensitization in response to highly potent, but not to less potent,
      nitrates. We therefore sought to support the hypothesis that bioactivation by
      ALDH-2 critically depends on the number of nitrate groups within the
      nitrovasodilator. EXPERIMENTAL APPROACH: Nitrates with one (PEMN), two (PEDN;
      GDN), three (PETriN; glyceryl trinitrate, GTN) and four (pentaerithrityl
      tetranitrate, PETN) nitrate groups were investigated. Vasodilatory potency was
      measured in isometric tension studies using isolated aortic segments of wild type
      (WT) and ALDH-2-/- mice. Activity of the cGMP-dependent kinase-I (reflected by
      levels of phosphorylated VAsodilator Stimulated Phosphoprotein, P-VASP) was
      quantified by Western blot analysis, mitochondrial dehydrogenase activity by
      HPLC. Following incubation of isolated mitochondria with PETN, PETriN-chromophore
      and PEDN, metabolites were quantified using chemiluminescence nitrogen detection
      and mass spectrometry. KEY RESULTS: Compared to WT, vasorelaxation in response to
      PETN, PETriN and GTN was attenuated about 10fold in ALDH-2-/- mice, identical to
      WT vessels preincubated with inhibitors of ALDH-2. Reduced vasodilator potency
      correlated with reduced P-VASP formation and diminished biotransformation of the
      tetranitrate- and trinitrate-compounds. None of these findings were observed for
      PEDN, GDN and PEMN. CONCLUSIONS AND IMPLICATIONS: Our results support the crucial
      role of ALDH-2 in bioactivating highly reactive nitrates like GTN, PETN and
      PETriN. ALDH-2-mediated relaxation by organic nitrates therefore depends mainly
      on the number of nitrate groups. Less potent nitrates like PEDN, GDN and PEMN are
      apparently biotransformed by other pathways.

PMID- 17220911
TI  - Statins induce S1P1 receptors and enhance endothelial nitric oxide production in
      response to high-density lipoproteins.
AB  - BACKGROUND AND PURPOSE: Sphingosine 1-phosphate (S1P) is a serum-borne naturally
      occurring sphingolipid, specifically enriched in high-density lipoprotein (HDL)
      fractions. S1P binds to G-protein-coupled S1P1 receptors to activate endothelial
      NO synthase (eNOS) in vascular endothelial cells. We explored whether and how
      statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors,
      modulate expression of S1P1 receptors and endothelial responses for subsequent
      stimulation with S1P or with HDL. EXPERIMENTAL APPROACH: Protein expression and
      phosphorylation and mRNA expression in cultured bovine aortic endothelial cells
      (BAEC) were determined using immunoblots and reverse transcription PCR analyses,
      respectively. NO synthesis was assessed as nitrite production. KEY RESULTS:
      Stimulation of BAEC with pitavastatin or atorvastatin led to significant
      increases in S1P1-receptors, at levels of protein and mRNA, in a dose-dependent
      manner. When BAEC were treated with pitavastatin prior to stimulation with S1P or
      with normal human HDL, phosphorylation and activation of eNOS evoked by S1P or by
      HDL was enhanced. These effects of statins were counteracted by L-mevalonate and
      were mimicked by an inhibitor of geranylgeranyl transferase I, suggesting that
      inhibition of HMG-CoA reductase activity and subsequent decreases in protein
      geranylgeranylation may contribute to these actions of statins. Specific knock
      down of S1P1 receptors by small interfering RNA led to attenuation of eNOS
      responses to HDL. CONCLUSIONS AND IMPLICATIONS: Statins induce S1P1 receptors and
      potentiate responses of endothelial cells to HDL-associated sphingolipids,
      identifying a novel aspect of the pleiotropic actions of statins through which
      they may exert NO-dependent vascular protective effects.

PMID- 17220912
TI  - JP-1302: a new tool to shed light on the roles of alpha2C-adrenoceptors in brain.
AB  - The discovery of JP-1302 as a selective, high affinity antagonist at the alpha2C
      adrenoceptor will enable researchers to probe the functional role and address the
      therapeutic utility of this potentially highly important adrenoceptor subtype.

PMID- 17220913
TI  - Pharmacological characterization and CNS effects of a novel highly selective
      alpha2C-adrenoceptor antagonist JP-1302.
AB  - BACKGROUND AND PURPOSE: Pharmacological validation of novel functions for the
      alpha2A-, alpha2B-, and alpha2C-adrenoceptor (AR) subtypes has been hampered by
      the limited specificity and subtype-selectivity of available ligands. The current
      study describes a novel highly selective alpha2C-adrenoceptor antagonist, JP-1302
      (acridin-9-yl-[4-(4-methylpiperazin-1-yl)-phenyl]amine). EXPERIMENTAL APPROACH:
      Standard in vitro binding and antagonism assays were employed to demonstrate the
      alpha2C-AR specificity of JP-1302. In addition, JP-1302 was tested in the forced
      swimming test (FST) and the prepulse-inhibition of startle reflex (PPI) model
      because mice with genetically altered alpha2C-adrenoceptors have previously been
      shown to exhibit different reactivity in these tests when compared to wild-type
      controls. KEY RESULTS: JP-1302 displayed antagonism potencies (KB values) of
      1,500, 2,200 and 16 nM at the human alpha2A-, alpha2B-, and alpha2C-adrenoceptor
      subtypes, respectively. JP-1302 produced antidepressant and antipsychotic-like
      effects, i.e. it effectively reduced immobility in the FST and reversed the
      phencyclidine-induced PPI deficit. Unlike the alpha2-subtype non-selective
      antagonist atipamezole, JP-1302 was not able to antagonize alpha2-agonist-induced
      sedation (measured as inhibition of spontaneous locomotor activity), hypothermia,
      alpha2-agonist-induced mydriasis or inhibition of vas deferens contractions,
      effects that have been generally attributed to the alpha2A-adrenoceptor subtype.
      In contrast to JP-1302, atipamezole did not antagonize the PCP-induced prepulse
      inhibition deficit. CONCLUSIONS AND IMPLICATIONS: The results provide further
      support for the hypothesis that specific antagonism of the alpha2C-adrenoceptor
      may have therapeutic potential as a novel mechanism for the treatment of
      neuropsychiatric disorders.

PMID- 17220915
TI  - Systemic infections and inflammation affect chronic neurodegeneration.
AB  - It is well known that systemic infections cause flare-ups of disease in
      individuals with asthma and rheumatoid arthritis, and that relapses in multiple
      sclerosis can often be associated with upper respiratory-tract infections. Here
      we review evidence to support our hypothesis that in chronic neurodegenerative
      diseases such as Alzheimer's disease, with an ongoing innate immune response in
      the brain, systemic infections and inflammation can cause acute exacerbations of
      symptoms and drive the progression of neurodegeneration.

PMID- 17220916
TI  - Activating and inhibitory functions of DAP12.
AB  - When associated with different receptors, the signalling adaptor DAP12 has been
      shown to both potentiate and attenuate the activation of leukocytes. But how can
      a protein with a single signalling motif elicit qualitatively different cellular
      responses? We describe a model of DAP12 function, whereby the quality of the
      cellular response (activation or inhibition) is modulated by the avidity of the
      interaction between the DAP12-associated receptor and its ligand. This model
      extends from previous studies of inhibitory signalling mediated by other
      adaptors, such as the Fc-receptor gamma-chain and CD3zeta, and provides a
      potential mechanism for the conflicting phenotypes observed in studies of DAP12
      deficient mice.

PMID- 17220914
TI  - Control of spasticity in a multiple sclerosis model is mediated by CB1, not CB2,
      cannabinoid receptors.
AB  - BACKGROUND AND PURPOSE: There is increasing evidence to suggest that cannabis can
      ameliorate muscle-spasticity in multiple sclerosis, as was objectively shown in
      experimental autoimmune encephalomyelitis models. The purpose of this study was
      to investigate further the involvement of CB1 and CB2)cannabinoid receptors in
      the control of experimental spasticity. EXPERIMENTAL APPROACH: Spasticity was
      induced in wildtype and CB1-deficient mice following the development of
      relapsing, experimental autoimmune encephalomyelitis. Spastic-hindlimb stiffness
      was measured by the resistance to flexion against a strain gauge following the
      administration of CB1 and CB2 agonists. KEY RESULTS: As previously suggested,
      some CB2-selective agonists (RWJ400065) could inhibit spasticity. Importantly,
      however, the anti-spastic activity of RWJ400065 and the therapeutic effect of non
      selective CB1/CB2 agonists (R(+)WIN55,212-2 and CP55, 940) was lost in spastic,
      CB1-deficit mice. CONCLUSIONS AND IMPLICATIONS: The CB1 receptor controls
      spasticity and cross-reactivity to this receptor appears to account for the
      therapeutic action of some CB2 agonists. As cannabinoid-induced psychoactivity is
      also mediated by the CB1 receptor, it will be difficult to truly dissociate the
      therapeutic effects from the well-known, adverse effects of cannabinoids when
      using cannabis as a medicine. The lack of knowledge on the true diversity of the
      cannabinoid system coupled with the lack of total specificity of current
      cannabinoid reagents makes interpretation of in vivo results difficult, if using
      a purely pharmacological approach. Gene knockout technology provides an important
      tool in target validation and indicates that the CB1 receptor is the main
      cannabinoid target for an anti-spastic effect.

PMID- 17220917
TI  - Lung function, oxygen saturation and symptoms among street sweepers in calabar
      Nigeria.
AB  - Chronic inhalation of dust impairs lung function and may cause respiratory
      symptoms. However, knowledge about the type of dust that can cause these problems
      is uncertain. Very little attention has been paid to the health of workers
      chronically exposed to dust raised by street sweeping without precautionary
      measures. Therefore, a study of lung function, oxygen saturation and symptoms
      among female street sweepers and their control groups in Calabar, Nigeria was
      carried out. Ventilatory function tests were done using 200 female street
      sweepers whose length of service was less than two years and 200 sex, age,
      weight, and height - matched external controls who were not exposed to any known
      air pollutant. The percentage of oxygen saturation (SPO((2)) of both the subjects
      and their control population was determined using a pulse oximeter. Respirable
      dust level in the test sites was 0.194 +/- 0.002 mu g/m3 and it was significantly
      higher (P < 0.001) than in control sites, which was 0.015 +/- 0.003 mu g/m3.There
      was no significant difference in the mean values of SPO((2))between the test and
      control subjects. However, there was also a significantly higher [P < 0.001]
      prevalence of back pain, cough, chest pain , catarrh and sneezing among the
      street sweepers compared to control. Lung function values, namely; FVC, FEV((1)),
      FEV((1)) % and PEFR were not significantly different in the two groups. Street
      sweeping; without precautionary measures may predispose to respiratory and non
      respiratory symptoms.

PMID- 17220918
TI  - Effect of Volume Loading with Water, Normal Saline, Palm Wine and Lipton Tea on
      Urinary Output, pH, Specific Gravity, Sodium and Potassium Concentrations in
      Human Subjects.
AB  - A comparative study of the diuretic effect of water, normal saline, palm wine and
      Lipton tea was carried out on forty (40) randomly selected, apparently normal
      undergraduate students of Medicine and Pharmacy at the University of Uyo,
      Nigeria. One and a half (1.5) litres of water, normal saline, palm wine and
      Lipton tea were given on separate days to the same subjects. The subjects were
      made to void their bladder before ingesting these substances and the urine sample
      collected was taken as control sample at the time zero. Thereafter, all the
      subjects emptied their bladder hourly for 3 hours. The urinary output, pH,
      specific gravity, sodium and potassium concentrations were determined. The
      results showed that water, palm wine and Lipton tea produced diuresis. Normal
      saline did not. Reduction of specific gravity and pH of urine accompanied these
      diuretic effects. Administration of normal saline and Lipton tea caused
      natriuresis. Potassium sparing diuresis was seen with Lipton tea and palm wine,
      whereas, water diuresis led to increased levels of potassium in urine. Volume
      loading with the above substances affected not only urinary output but also renal
      handling of sodium and potassium ions.

PMID- 17220919
TI  - The effects of environmental assaults on human physiology (1).

PMID- 17220920
TI  - Innovative strategies in teaching of biomedical sciences to health professionals.
AB  - Knowledge and skills in biomedical sciences have reached a level, which is
      difficult to pass on to students in the traditional one to two years by
      traditional lecture methods and are still expanding. Recently, innovative methods
      of enabling the students to acquire the knowledge and skills have been evolved,
      and include student-centered and problem-based learning strategies, among others.
      These are strategies in which the student is taught how to learn for him/her self
      and then becomes responsible for his/her own learning with a certain minimum
      amount of guidance from the teachers. Other advantages of using these strategies
      of learning and teaching include development of competencies in continuous self
      and peer evaluation, self-directed learning leading to continuing medical
      education for life, team work, professionalism and professional ethics. These
      strategies also increase the chances of attitudinal molding, enhancing good
      personal characteristics while discouraging bad ones. Communication skills are
      greatly enhanced.

PMID- 17220921
TI  - The effects of environmental assaults on human physiology (2).

PMID- 17220922
TI  - Current developments in the physiology and management of asthma.

PMID- 17220923
TI  - Effect of Ingestion of Ethanol Extract of Garcinia Kola Seed on Erythrocytes in
      Wistar rats.
AB  - The objective of this study is to investigate the effect of ingestion of crude
      ethanol extract of Garcinia kola seed on erythrocytes. Fifty male Wistar rats
      with average weight of 200g were divided into 5 treatment groups of 10 rats per
      group. Group A, served as the control and was fed with standard animal feed only
      while groups B, C, D and E which were the treatment groups, in addition were
      force-fed 2 g/kg/rat/day of the Ethanol extract of Garcinia kola seed for 1, 2,
      3, and 4 weeks respectively by means of an endogastric tube and syringe. At the
      end of the experimental period for each group the animals were sacrificed and the
      erythrocyte number, packed cell volume (PCV), and heamogloin concentration values
      were determined. The result on analysis showed that erythrocyte-count, PCV and
      haemoglobin concentration values showed significantly decreased values [P < 0.05]
      between group B (week 1) and Group A, but groups C, D and E values showed a
      steady rise which were not significant [P < 0.05] when compared with Group A.
      None of the values fell below the normal physiological range of the experimental
      animals. This shows that Garcinia kola seed which has flavonoids as its active
      constituent has no long term significant toxicological implication with respect
      to the concentration given on the erythrocytes of mammals.

PMID- 17220924
TI  - Sex variations in the haemorheological parameters of some hypertensive nigerians
      as compared to normotensives.
AB  - Sex variations in some haemorheological parameters: Haematocrit (Hct),
      Erythrocyte Sedimentation Rate (ESR), Hemoglobin concentration (Hbc), Fibrinogen
      concentration (FC), Relative Plasma Viscosity (RPV) and Whole Blood Relative
      Viscosity (WBRV) were determined in 30 male and 20 female hypertensive subjects
      without complications, aged between 30 and 70 years. 30 male and 20 female
      normotensive subjects aged between 29 and 71 years, matched for age, weight and
      height with the hypertensive group served as control. In both groups all the
      parameters were determined using methods previously described by various workers.
      Results obtained in normotensives showed a significantly lower systolic blood
      pressure, mean arterial pressure, haematocrit and whole blood relative viscosity
      and a significantly higher erythrocyte sedimentation rate in female subjects
      compared to male subjects, no significant correlation was found between any of
      the haemorheological parameters and the blood pressure indices in both sexes. In
      the hypertensives, only whole blood relative viscosity was found to be
      significantly higher in females compared to males. In male hypertensives
      significant positive correlations were found between erythrocyte sedimentation
      rate and all the blood pressure parameters and between relative plasma viscosity
      and systolic and mean arterial pressures; negative correlations were found
      between haematocrit and systolic and mean arterial pressures. In female
      hypertensives there were positive correlations between relative plasma viscosity
      and all the blood pressure parameters and between whole blood relative viscosity
      and systolic blood pressure. The present study confirms that significant sex
      variations occur in the various haemorheological parameters in both normotensive
      and hypertensive Nigerian subjects.

PMID- 17220925
TI  - Efficacy of aqueous leaf extract of vernonia amygdalina on plasma lipoprotein and
      oxidative status in diabetic rat models.
AB  - Many minor components of foods, such as secondary plant metabolites, have been
      shown to posses antioxidant activities, improving the effects of oxidative stress
      on diabetes and other disease conditions. This study evaluates the effect of
      aqueous extracts from Vernonia amygdalina leaves on lipid profiles and oxidative
      stress in streptozotocin induced diabetic rats. The results showed that the
      streptozotocin induced diabetic rats were subjected to oxidative stress as was
      shown by the extent of lipid peroxidation (high malondialdehyde levels) present
      in the plasma. The aqueous extract of V. amygdalina leaves possessed antioxidant
      activity as shown by decreases in malondialdehyde levels. High values of LDL
      cholesterol and triglycerides levels, which are typical of the diabetic
      condition, were also found in streptozotocin induced diabetic rats. The aqueous
      extract also significantly reduced triglyceride levels and normalized cholesterol
      concentrations. This shows that the aqueous extract of V. amygdalina leaves have
      both hypolipidaemic and antioxidant properties.

PMID- 17220926
TI  - Exercise performance in relation to glucose drink and their effect on some
      biochemical parameters.
AB  - This study was designed to determine the effect of glucose drink on marathon
      running and on some biochemical parameters. Seven untrained athletes (male
      students) participated in this study and were engaged in marathon running with
      and without intake of glucose drink (1 g/kg body weight) in a double blind
      procedure. Blood samples were collected at 0, 30, 60 and 150 minutes for serum
      glucose, triglyceride, cholesterol and PCV estimation. There were significant
      increases in serum glucose (F=13.01) [P < 0.01]; and triglyceride (F=6.87); [P <
      0.01] following pre-exercise glucose drink, while PCV remained unchanged with or
      without pre-exercise glucose drink. Greater than 80 % of the subjects covered
      more distance with glucose intake, than without glucose drink. It is concluded
      that carbohydrate intake prior to exercise may enhance exercise performance and
      spares glycogen and lipid utilization.

PMID- 17220927
TI  - The effects of menopause on the serum lipid profile of normal females of South
      East Nigeria.
AB  - Dyslipidemia in menopause is a known feature in women, whether it leads to
      significant increase in the development of coronary heart disease (CHD) is still
      controversial, more so in our environment where little work has been done. The
      present study is aimed at comparing the level of total serum cholesterol,
      including its subunits in premenopausal with that of their postmenopausal
      counterparts. This is to enable us ascertain the relative risk of developing
      cardiovascular disease in postmenopausal women in our environment. One hundred
      and twenty six (126) apparently healthy, non-pregnant females (74 premenopausal
      and 52 postmenopausal) were recruited for the study. Serum total cholesterol and
      their subfractions- high-density lipoproteins (HDL), low-density lipoproteins
      (LDL), very low-density lipoproteins (VLDL) and triglycerides (TG) were estimated
      using enzymatic and established mathematical methods. There was no significant
      difference in the total serum cholesterol and triglyceride between the two
      groups. There was however, a significant reduction of HDL and VLDL in the
      postmenopausal group [P < 0.005] and a significant increase in the level of LDL
      in the postmenopausal group [P < 0.005]). The elevated LDL and the reduction of
      cardio protective HDL and VLDL is an indication that menopause is an independent
      risk factor for developing cardiovascular disease in our environment.

PMID- 17220928
TI  - The reproductive dysfunction effects of gasoline inhalation in albino rats.
AB  - Daily exposure to fuel vapour may pose significant health risk to exposed
      individuals. Fifteen each of male and female albino rats weighing between 110
      230g were divided into test (10) and control (5) groups each. The test animals;
      were exposed to inhalation gasoline for one hour daily for twenty-one consecutive
      days. All animals were then bled and the serum levels of the reproductive
      hormones determined. The results showed significant [P < 0.05] reduction in the
      serum levels of all the hormones of reproduction in both the male and female test
      animals. The results suggest that inhalation gasoline exposure significantly [P <
      0.05] lowers the levels of reproductive hormones in albino rats and may thus
      interfere with reproduction.

PMID- 17220929
TI  - Effects of garcinia kola seed extract on ovulation, oestrous cycle and foetal
      development in cyclic female sprague-dawley rats.
AB  - The effects of Garcinia kola (G. kola) seed extract on oestrous cycle, ovulation
      and foetal development were studied in adult female Sprague-Dawley (S-D) rats.
      Cyclic female rats weighing 150 to 200 g were divided into three experimental
      groups and a control group. Group 1 was fed with 200 mg/kg body weight of the
      extract on proestrous. Group 2 received 200 mg/kg body weight of the extract
      daily for six weeks, while group 3, consisted of pregnant rats which received the
      same dose of the extract on days 1-5, 7-9 (th), 13 (th), and 14 (th), day of
      gestation. In groups 1 and 2, vaginal lavage was taken daily to monitor the
      oestrous cycle and ovulation. In group 3, gestational parameters monitored were
      number of total implants, resorption and dead foetuses. Live foetuses were
      weighed and examined for external malformation and variation. The results showed
      that the oestrous cycle was altered for the first two weeks after commencement of
      extract but returned to normal from the third week. This was indicated by the
      irregular pattern of oestrous with a prolonged dioestrus observed in the treated
      rats. Ovulation was partially blocked as shown by the reduced number of ova
      observed in the oviduct from the treated rats compared with control [P < 0.05].
      There was a significant decrease in the weight of foetuses from the treated rats
      [P < 0.05]; while foetuses from pregnant rats (7 %) which received treatment for
      the first five days of gestation, had malformed left upper limb. Results suggest
      that G. kola seed at 200 mg/kg body weight administered alters oestrous cycle in
      rats, partly inhibits ovulation and may produce duration dependent teratogenicity
      in foetal rats.

PMID- 17220930
TI  - Factors Influencing the Incidence of Pre-term Birth in Calabar, Nigeria.
AB  - Women who had pre-term birth in the University of Calabar Teaching Hospital,
      Calabar, over a two and a half year period were studied. The aim was to establish
      the factors influencing the incidence of pre-term birth in Calabar. Factors which
      significantly increase the incidence of pre-term delivery included: previous
      induced abortion [P < 0.0001], nulliparity [P < 0.001], out of wedlock birth [P <
      0.05] and lack of antenatal care [P < 0.01]. Women with multiple pregnancy [P <
      0.001] or previous pre-term delivery [P < 0.01], have a significantly high risk
      for pre-term birth. Antenatal complications [P < 0.0001] particularly anaemia [P
      < 0.001] or malaria [P < 0.05] in the index pregnancy constitute risk factors for
      pre-term delivery. However, educational status, social class and previous
      spontaneous abortion did not seem to significantly influence the incidence of pre
      term birth in this study [P < 0.05]. Wider use of family planning, less
      restrictive abortion laws and training of doctors and nurses on the use of manual
      vacuum aspiration in the management of post-abortion complications may help
      reduce the incidence of pre-term birth in Calabar. Replacing pyrimethamine
      chemoprophylaxis for malaria in pregnancy by intermittent treatment of malaria
      with sulphadoxine-pyrimethamine and deworming our women during antenatal care may
      also help reduce the incidence of pre-term birth in our community.

PMID- 17220931
TI  - Preliminary studies on effect of chloroquine phosphate on gastric acid secretion
      in rats.
AB  - It is not certain whether chloroquine-induced pruritus is mainly attributable to
      the liberation of histamine, a powerful gastric acid secretagogue from mast
      cells, which may not be beneficial in peptic ulceration. Therefore, the aim of
      this study was to find out whether chloroquine (CQ) can stimulate gastric acid
      secretion in the rat. Gastric acid output was measured by the continuous
      perfusion of rats stomachs under anaesthesia with normal saline at the rate of
      1ml per minutes. Thirty albino rats were divided into five groups of six rats
      each. Three groups had intraperitoneal administration of the following; normal
      saline (1 ml/kg control), CQ (3 microgram/kg; test) and Histamine H2 receptor
      antagonist, Ranitidine [4 microgram/kg] following CQ administration respectively.
      The other two groups had subcutaneous administration of histamine (100
      microgram/kg) alone and histamine following CQ administration respectively. The
      basal acid secretion, (4.71+/- +/- 0.05 mMol/10mins) in a group of rats was not
      significantly increased in comparison with the peak acid output [P < 0.05]
      following normal saline administration (1 ml; ml/kg; i.p.). Administration of CQ
      in a second group;significantly increased acid secretion to a peak of 7.2 +/- 1.7
      mMol/10mins [P < 0.05]. Ranitidine blocked CQ -induced acid secretion in a third
      group. Histamine significantly increased acid secretion from control level of
      4.85 +/- 0.14 mMol/10mins to 51.67 +/- 5.07 mMol/10mins [P < 0.001] in a fourth
      group, while CQ administered 2mins after histamine administration significantly
      increased acid level from 4.72 +/- 0.12 mMol/10mins to peak at 20.63 +/- 3.28
      mMol/10mins [P< 0.001] in a fifth group of rats. The peak acid output in the
      fifth group was significantly lower than that obtained with histamine alone. In
      conclusion, chloroquine is a weak stimulant of gastric acid secretion rats. It
      inhibits histamine-stimulated acid secretion probably by occupying histamine H
      (2) receptors in rats.

PMID- 17220932
TI  - Influence of nitric oxide on histamine and carbachol-induced gastric Acid
      secretion in the common african toad - bufo regularis.
AB  - The study aimed to determine the influence of nitric oxide (NO) on the action of
      histamine and carbachol on acid secretion in the common African toad - Bufo
      regularis. Gastric acidity was determined by titration method. The acid secretion
      was determined when nitric oxide was absent following administration of NO
      synthase inhibitor; N-nitro-L-arginine methyl ester (L-NAME) and when nitric
      oxide was in excess by administration of exogenous NO donor, sodium nitroprusside
      (SNP). Histamine or carbachol increased acid secretion in the toad. Acid output
      increased from 0.32 +/- 0.04 mEq/15min to 0.56 +/- 0.08 and 0.61 +/- 0.05
      mEq/15min for histamine and carbachol respectively [P < 0.05]. Pretreatment of
      the toad with L-NAME produced further increases in histamine (0.62 +/- 0.06
      mEq/15min) or carbachol (0.74 +/- 0.06 mEq/15min) induced acid secretion
      respectively. SNP however, completely abolished the acid secretion stimulated by
      either histamine or carbachol. It was therefore concluded that nitric oxide has a
      negative influence on the histamine or carbachol-stimulated acid secretion in the
      toad - Bufo regularis.

PMID- 17220933
TI  - Variations of peak expiratory flow rate with anthropometric determinants in a
      population of healthy adult nigerians.
AB  - Peak expiratory flow rate (PEFR) was measured in 300 healthy adult male and
      female staff and students of the University of Benin, Benin City, and the College
      of Education, Ekiadolor, near Benin. The variations of Peak Expiratory Flow Rate
      with respect to height (ht), weight (wt) and chest circumference (cc) were
      determined in these subjects. PEFR values fell within the middle to the lower
      limits of the range for the general male and female populations. There was a
      linear increase in PEFR with respect to the three anthropometric variables (ht,
      wt and cc) only in the young adult males, whereas in the older adult males and
      females, PEFR fluctuated considerably with the variables. PEFR correlates more
      with height, weight and chest circumference in young adults than in older adults.
      Respiratory function indices collected from healthy young adults may be more
      reliable and predictable than those from older adults.

PMID- 17220934
TI  - Effect of ovariectomy on the level of plasma sex hormones in albino rats.
AB  - The study was carried out to evaluate the levels of sex hormones (testosterone,
      progesterone and estradiol), six weeks post normal ovariectomy as against
      estimating the levels immediately or less 48 hours after operation. 28 adult
      female albino rats of Wistar strain were used. They were fed twice a day with
      Guinea pellets and tap water was offered ad libitum. The animals were grouped
      into three. Group one was sham operated and served as the control, group two was
      unilaterally ovariectomised (right removed), group three was bilaterally
      ovariectomised. The animals were sacrificed at the end of the study by
      decapitation and the blood collected and assayed for sex hormones. The levels of
      the sex hormones were measured using radioimmunoassay technique. The results
      showed significant increase in testosterone level in group 3 with decrease in
      group 2 which was not significant when compared to group 1. On the progesterone
      levels, there were significant decrease in group 3 and not 2 when compared to
      group 1. Estradiol level showed significant decrease in only group 3. The
      decrease in group 2 was not significant when compared with the control. This work
      therefore does not propose a longer period of hormonal estimation beyond 48 hours
      following ovariectomy as the results obtained 6 weeks post ovariectomy did not
      differ or alter significantly beyond 48 hours when compared with the work of Bast
      and Greenwald 1977, Bulcher 1977, De Jong et al 1978. It is therefore concluded
      that sex hormone values obtained 6 weeks after normal ovariectomy did not differ
      significantly as was observed by various workers and confirmed by the present
      study.

PMID- 17220935
TI  - Dependence of calcium on thyroid hormone for the regulation of cellular
      functions.
AB  - Recently, the thyroid hormone has been shown to cause increase in calcium ion
      (Ca(2+)) concentration by mobilizing intracellular calcium((2+)). The
      mobilization of intracellular calcium((2+)) in the absence of transmembrane
      calcium((2+)) influx has been accepted as evidence for a cell-surface Ca((2+))
      receptor. The possible role of thyroid hormone in the regulation of cellular
      functions by ca((2+)-channel was investigated using parameters proven to
      indispensably involve Ca(2+). Bleeding and clotting times and rat uterine muscle
      activity in Ca(2+)-free Tyrode's solution. Adult female Wistar rats divided into
      four groups, namely; (i) Control, (ii) Thyroidectomized, (iii) Throidectomized
      treated with thyroxine and (iv) Thyroxine-treated; were fed on rat chow. While
      groups i and ii were allowed access to tap water ad libitum for 60 days, groups
      iii and iv received tyroxine (10 mg/kg body weight) every alternate day and tap
      water ad libitum for 60 days. All groups were kept in an air-conditioned room
      till they were euthanized. The results showed that thyroxine elicited biphasic
      contraction in Ca (2+)-depletion and potentiated uterine contraction during
      Ca(2+)-loading (P < 0.001). Inhibition of contractions in thyroidectomy, showed
      dependency of Ca (2+) on thyroid hormones for the regulation of cellular
      functions.

PMID- 17220936
TI  - The role of GABA(A) and GABA(B) receptors in the control of GnRH release in
      anestrous ewes.
AB  - The paper reviews data concerning the involvement of GABA(A) and GABA(B)
      receptors in the control of GnRH secretion in anestrous ewes. Generally, GABA
      influences the GnRH release through GABA(A) and GABA(B) receptors located on
      perikaria of the GnRH neurons in the preoptic area (MPOA) or through the
      influence on beta-endorphinergic and catecholaminergic systems activity in MPOA
      and in ventromedial-infundibular region of the hypothalamus (VEN/NI). Stimulation
      of GABA(A) receptors in VEN/NI and MPOA attenuates GnRH release, while activation
      of GABA(B) receptors in MPOA decreases GnRH secretion, and in VEN/NI increases
      concentration of GnRH. The different neural mechanisms could be involved in this
      process: direct ligand action on the GABA(A) and GABA(B) receptors located on
      GnRH cells and axon terminals or indirect effect through the changes in the beta
      endorphinergic and catecholaminergic systems activity in these structures of the
      brain.

PMID- 17220937
TI  - Effects of dietary fat on androgen secretion and metabolism.
AB  - In humans and animals, food composition, especially dietary fat, affects androgen
      secretion and metabolism. On the other hand, disturbances of sex steroid
      metabolism play an important role in the etiology of hormone-related cancers. In
      this report the roles of dietary fat, its quantity, fatty acid composition and
      feeding period on androgens metabolism was described. In conclusion, it should be
      stated that the amount of dietary fat, and its composition, (i.e. the content of
      individual fatty acids and/or their groups), as well as the period during which
      the nutrient is fed to animals affect significantly the secretion and metabolism
      of androgens.

PMID- 17220938
TI  - Neuropeptide Y--a neuromodulatory link between nutrition and reproduction at the
      central nervous system level.
AB  - The deficiency of nutrients in mammals' diets results in impaired gonadal
      function, especially in restraining of processes leading to puberty and
      disturbances in the course of the estrous cycle. The decreased GnRH/LH pulsatile
      secretion has been proposed as the most important etiological factor for
      nutritionally induced suppression of pituitary-ovarian functions. Although the
      relationship between nutrition and reproduction has been extensively
      investigated, little information exists about the exact mechanism connecting
      these two processes. One of the candidates is neuropeptide Y (NPY), synthesized
      in the hypothalamus. In the present paper, we reviewed the distribution of the
      NPY neurons, its receptors, contacts with other hypothalamic centers and its
      orexigenic properties. Next, we discussed the participation of NPY in the
      regulation of GnRH/LH secretion and underlined its dual role in the control of
      the reproductive system and nutritional state of organism. This information
      confirmed the hypothesis that NPY can be a candidate for a link between nutrition
      and reproduction at the level of the central nervous system.

PMID- 17220939
TI  - Orexin A and its role in the regulation of the hypothalamo-pituitary axes in the
      rat.
AB  - Orexin A (OxA), a recently discovered neuropeptide, is synthesized mainly by
      neurons located in the posterolateral hypothalamus and is a 33 amino acid peptide
      with N-terminal pyroglutamyl residue and two inter-chain disulfide bonds. It is a
      potent agonist for both the orexin-1 (OxR1) and orexin-2 (OxR2) receptors. Orexin
      A and its receptors are widely distributed in the central nervous system (CNS)
      and peripheral organs suggesting the pleiotropic functions of this peptide.
      Orexin A is involved in food intake and energy expenditure in many species, but
      also plays an important role in the regulation of the hypothalamo-pituitary axes.
      The role of orexin A in the regulation of the hypothalamo-pituitary-adrenal, 
      thyroid, -somatotropic, and -gonadal axes has been inadequately investigated.
      Orexinergic fibres project to the septal-preoptic and arcuate nucleus-median
      eminence regions--two areas of the brain directly involved in the synthesis and
      release of gonadotropin-releasing hormone (GnRH). Contentious opinions concerning
      the influence of orexin A over the hypothalamo-gonadotropic axis have been
      reported in both in vivo and in vitro studies. Further studies are necessary to
      clarify relationships between orexin A and the hypothalamo-pituitary hormones
      involved in reproduction.

PMID- 17220940
TI  - Effect of prolonged progesterone treatment on the proenkephalin mRNA gene
      expression and enkephalins concentration in the sheep brain.
AB  - The opioids modulate reproduction in sheep mostly by inhibiting the activity of
      the hypothalamo-pituitary-gonadal axis. However, the mechanism by which the
      negative feedback control systems regulate opioid synthesis and secretion in
      sheep is still not recognized. As a part of a research dealing with interaction
      between opioids and steroids, the effect of prolonged administration of
      progesterone (P4) and opioid receptor agonist or antagonist on the Met-enkephalin
      synthesis and concentration was examined in sheep brain. Long term P4 treatment
      significantly decreased the synthesis and the concentration of the opioid peptide
      in the hypothalamus and pituitary, however, the effect was more pronounced in the
      hypothalamus. Injections of Met-enkephalin completely or partially reversed the
      effect of P4. Naltrexone given together with opioid peptide modulated the
      response to the opioid agonist. The results show that there is an interaction
      between P4 and endogenous opioids in the central nervous system of cyclic sheep.

PMID- 17220941
TI  - Phytoestrogen action in Leydig cells of Bilgoraj ganders (Anser anser).
AB  - The mechanism of phytoestrogen action in gonadal cells of ganders has not been
      elucidated. The aim of the study was to investigate in Bilgoraj ganders the
      possibility of phytoestrogen action via estrogen or androgen receptors or via
      protein tyrosine kinase pathways in Leydig cells. Genistein and daidzein (5 and
      50 microM) as well as equol (50 microM) inhibited testosterone (T) secretion by
      incubated Leydig cells (1x10(5)/ml; 20 h; 37 degrees C). The effects of
      hydroxytamoxifen (estrogen receptor inhibitor) and cyproterone acetate (androgen
      receptor antagonist) on phytoestrogen inhibition of T release by Leydig cells
      were not observed. Lavendustin A (protein tyrosine kinases inhibitor) did not
      change T production. The influence of phytoestrogens seems not to be conducted
      via estrogen and androgen receptors or protein tyrosine kinases system in these
      cells, but further studies are required to completely examine the mechanism of
      phytoestrogens action in testes of ganders.

PMID- 17220942
TI  - Acid glycosidases in the isthmus of the hen oviduct and egg shell membranes.
AB  - Specific activities of seven acid glycosidases: beta-hexosaminidase, alpha- and
      beta-galactosidase, alpha- and beta-mannosidase, alpha-glucosidase and alpha
      fucosidase were determined in various parts of the domestic hen oviduct
      (infundibulum, isthmus, shell gland and vagina). The activity of most enzymes was
      the highest in the isthmus. Multiple forms of all acid glycosidases from the
      isthmus were separated by strong anion exchange chromatography at pH 6.0. The
      isoelectric points of the isthmus forms of beta-hexosaminidase, beta
      galactosidase and alpha- and beta-mannosidase were determined by
      chromatofocusing. For the first time the high beta-galactosidase activity was
      found in hen egg shell membranes.

PMID- 17220943
TI  - Distribution of acid glycosidases in the male genital tract of the pheasant.
AB  - The distribution of the activity of seven acid glycosidases in the reproductive
      organs of the pheasant (Phasianus colchicus) was studied. The study was carried
      out on seven mature birds at the age of 11 months during the reproductive season
      (May). Significant (p<0.01) differences in acid glycosidase activity dependent on
      enzyme origin were observed. Generally, the highest activity of acid glycosidases
      was found in the epididymis, intermediate in the ductus deferens and the lowest
      in the testes. Exceptionally, alpha-mannosidase had the highest activity in the
      ductus deferens. Anion-exchange chromatography elution profiles of most enzymes
      from the tested reproductive organs were similar, however evident differences
      were observed for beta-mannosidase forms.

PMID- 17220944
TI  - Ovulation level and prolificacy in ewes depending on their age, birth type and
      percentage of prolific genotype.
AB  - During December mating periods of 2000-2003, wool and meat breeds crossed with
      East Friesian milk sheep and rams of prolific breeds (Finn or Romanov) were
      examined laparoscopically. Ovine ovaries were examined between 4 and 9 days after
      mating. The litter size was recorded and compared with the number of ovulations.
      The fertility of the analyzed animals was 69.6%, with 192.6% prolificacy. The
      difference between the average number of corpora lutea found on ovaries and the
      mean number of lambs born was 0.35 and ranged from 0.32 to 0.41 according to age
      group, from 0.22 to 0.41 according to sheep birth type, and from 0 to 0.52 lamb
      per ewe according to percentage of prolific breeds.

PMID- 17220946
TI  - Morphometrical studies of reproductive system of birds after treatment with
      dopamine receptor blockers and melatonin.
AB  - Male Japanese quails were treated with melatonin alone or melatonin combined with
      D1 and D2 dopamine receptor blockers. Following the treatment, hypothalamus,
      pituitary glands and testes were analyzed morphometrically. The results suggest
      the existence of an interaction between melatonin and dopaminergic system in the
      brain in the regulation of reproductive processes in immature birds. The
      character of this interaction alters according to the time of the treatment
      (morning, afternoon, evening, night).

PMID- 17220947
TI  - Evaluation of males spermiogram in domestic pigs.
AB  - A microscopic assessment was used to estimate sperm morphological structure in
      405 ejaculates from 70 boars according to Blom classification. The classification
      of spermiogram quality according to a new 6-degree scale was also established. We
      found, that male spermiograms in domestic pigs were characterized by a large
      variability both between and within breeds. The estimation of semen quality, only
      with regard to the mean frequency of occurrence of particular morphological forms
      of spermatozoa, was not effective for evaluation of individual boar or group of
      boars. However, the method was effective to evaluate individual ejaculates. The
      quality classification of the spermiogram enabled to evaluate usefulness of
      ejaculates graded as good and average for insemination.

PMID- 17220945
TI  - The interaction of the thyroid gland, pineal gland and immune system in chicken.
AB  - The interaction of immunological system, thyroid and pineal gland was studied in
      5-week old males of Gallus domesticus. Several morphometrical parameters in
      pineal and thyroid glands were measured after bird immunization with human red
      blood cells and/or treatment with melatonin or seduxen, melatonin receptor
      blocker. The peak of the thyroid activity was found on Day 7 after immunization.
      The immune system appears to directly activate the thyroid gland only in the
      presence of certain level of melatonin. We suggest that the melatonin mechanism
      of action includes the enhancement of thyroid gland sensitivity to immune
      factors. Seduxen prevented the stimulatory influence of the immune system on the
      thyroid gland.

PMID- 17220948
TI  - Sperm morphology of cattle and domestic pigs.
AB  - Sperm morphology was evaluated (using Blom classification) in 44 ejaculates of 11
      bulls and 44 ejaculates of 11 boars. Significant differences in sperm morphology
      were found between bulls and boars. In addition, the correlations between
      frequency of morphological changes and morphometrical traits of boar spermatozoa
      were demonstrated. More morphological anomalies of spermatozoa were recorded in
      ejaculates containing longer spermatozoa.

PMID- 17220949
TI  - Localization of chorionic pregnancy-associated glycoprotein family in the pig.
AB  - The objective of this study was to localize the immuno-positive porcine PAG
      (pPAG) proteins within chorionic cells throughout the intensive placenta
      development as pregnancy advances (16-61 days post coitum - dpc). Placental
      sections were used for double fluorescent histochemistry with selected primary
      rabbit anti-pPAG sera. The polyclonals were created against recombinant pPAG2
      antigen or various secretory porcine native chorionic antigens produced in vitro.
      Among placental cells stained with fluorescent propidium iodine, the positive
      pPAG immuno-complexes were visualized by Alexa 488 fluorochrom - conjugated to
      secondary anti-rabbit goat immunoglobulins. This is the first report concerning
      cellular localization of the pPAG protein family within diffuse epitheliochorial
      placenta development throughout the first half of pregnancy in the pig.
      Fluorescent immuno-positive pPAG signals have been restricted to chorionic cell
      layers (branched mushroom-like and finger-like structures) that generate a
      epitheliochorial feto-maternal surface augmented by maternal endometrium
      interdigitations with the gestation progress in the pig. These results suggest
      that the pPAG proteins robustly expressed in chorionic cells are involved in the
      regulation of intensive development of diffuse porcine placenta during the first
      half of pregnancy.

PMID- 17220950
TI  - Effects of dietary supplementation with omega-3 polyunsaturated fatty acids on
      some reproductive characteristics in gilts.
AB  - The main objective of this study was to determine the effects of dietary
      supplementation with omega-3 polyunsaturated fatty acids on ovulation rate and
      litter size at day 27 post-mating in gilts. Estrous cycles were synchronized in
      crossbred gilts (n=48) using a progestin (Matrix; Intervet America Inc.,
      Millsboro, DE, USA), fed at a rate of 15 mg/day for 18 days. Following progestin
      withdrawal, gilts were checked for estrus twice daily and mated by artificial
      insemination. At 27 days post-mating, gilts were killed and reproductive tracts
      collected and examined. Beginning 17 days before the initiation of progestin
      therapy and continuing until slaughter, gilts were fed 2.27 kg of a basal diet
      (n=24) or the basal diet supplemented with 1% Fertilium (JBS United, Inc.,
      Sheridan, IN) (n=24), a source of omega-3 polyunsaturated fatty acids. All gilts
      in the treatment and control groups were pregnant as evidenced after examination
      of dissected reproductive tracts at approximately 27 days post-mating. Ovulation
      rate (17.5 vs. 17.9; SEM=0.5; p=0.61), number of embryos (14.5 vs. 14.3; SEM=0.6;
      p=0.77), embryo weight (1.11 vs. 1.14 g; SEM=0.02; p=0.45), and crown-rump length
      (26.4 vs. 26.9 mm; SEM=0.27; p=0.28), were similar for control and Fertilium-fed
      gilts, respectively. Backfat thickness at day 27 post-mating was greater (p<0.01)
      for Fertilium-fed gilts (14.0+/-0.5 mm) compared with controls (12.3+/-0.5 mm).
      The present treatment with Fertilium for the period of approximately 61 days did
      not alter ovulation rate and litter size at day 27 post-mating in gilts.

PMID- 17220951
TI  - Follicular wave status at the beginning of the FSH treatment modifies
      reproductive features in superovulated sheep.
AB  - In the current study we investigated whether the developmental status of the two
      largest follicles (LF1 and LF2) at the time of administration of the first two
      doses (0 and 12 h) of FSH of a superovulatory treatment influences periovulatory
      events and embryo yields in sheep. A larger size of LF1 was negatively correlated
      with embryo recovery (r=-0.608 for 0 h and r=-523 for 12 h, p<0.05),
      fertilization (r=-0.464 for 12 h, p<0.05) and viability (r=-0.775 for 12 h,
      p<0.005). Embryo viability rates were also lower when a higher difference between
      LF1 and LF2 (r=-0.839 for 0 h and r=-0.761 for 12 h, p<0.01) and a smaller size
      of LF2 (r=0.877 for 0 h and r=0.622 for 12 h, p<0.01) were observed. This
      indicates the existence of a limit in the follicular size that will be able to
      give rise a viable embryo. Conversely, a larger size of LF2 at the time of
      administration of the first two FSH doses was correlated with reduced recovery
      rates (r=-0.884 for 0 h and r=-0.706 for 12 h, p<0.01), whilst a decreasing size
      of LF1 and LF2 was correlated with an increased ovulation rate and recovered
      embryos. The dominance effect appeared to affect the timing of the preovulatory
      LH surge. Ewes with a higher difference between LF1 and LF2 displayed earlier LH
      surges (r=-0.420 for 0 h and r=-0.401 for 12 h, p<0.05) which were related to a
      higher number of non viable embryos (r=-0.777, p<0.05). The fact that
      superovulatory yields were affected by, both LF1 and LF2 supports the hypothesis
      of co-dominance effects in sheep.

PMID- 17220952
TI  - Serum concentrations of immunoglobulins and acute phase proteins in Nigerian
      women with preeclampsia.
AB  - Preeclampsia is a pregnancy-specific condition that increases maternal and infant
      mortality and morbidity. It is diagnosed based on a triad of hypertension,
      significant proteinuria and rapidly increasing edema during gestation. The
      factors that initiate preeclampsia are unknown and still a subject of intense
      clinical research. The objective of this study is to provide additional
      immunological information about preeclampsia. To achieve this, humoral
      immunochemical parameters such as three classes of immunoglobulin (IgA, IgG and
      IgM) and three acute phase proteins (alpha 2-macroglobulin, haptoglobin and
      transferrin) were measured by single radial immunodifussion method in 32 pregnant
      women with preeclampsia, 36 pregnant women without preeclampsia and 24 non
      pregnant women (controls). Total protein in the urine was also determined by
      spectrophotometric method. In women with preeclampsia, the levels of IgG, IgA,
      transferrin and alpha 2-macroglobulin were significantly reduced compared with
      subjects with normal pregnancy, but the level of haptoglobin was significantly
      raised in preeclampsia compared with women having normal pregnancy. Urinary total
      protein and IgG were significantly raised in Nigerian women with preeclampsia
      compared with non-pregnant controls. There were significant negative correlations
      between serum IgG, IgA and urinary protein. The possible involvement of
      immunoglobulins and acute phase proteins in preeclampsia is discussed.

PMID- 17220953
TI  - Differential effects of soy-containing diets on the reproductive tissues growth
      and reproductive hormone secretion in male rats.
AB  - The effects of feeding a breeding diet containing soy products to pregnant and
      lactating females on reproductive tissues and secretion of the reproductive
      hormones in their male progeny, immediately after weaning (postnatal day - PND
      22) and after reaching puberty (PND 60) were studied. Similarly, the response of
      adult males to a soy maintenance diet over shorter (PND 160) and longer (PND 280)
      periods of time was examined. The relative weights (standardized by body weight)
      of the testes, epididymis and prostate, and the concentrations of luteinizing
      hormone (LH), testosterone and prolactin (PRL) were used as the examined
      endpoints. In rats on PND 22, no significant differences in the relative organs
      weights and the plasma hormones concentrations were found between the
      experimental and control groups. In rats on PND 60 which continued consuming a
      soy breeding diet, the relative tissue weights did not differ significantly,
      while the mean plasma LH and PRL concentrations were higher (p<0.01-0.001)
      compared to the controls. In rats on PND 160 fed soy maintenance diet, the higher
      relative testes (p<0.01) and epididymis (p<0.05) weights as well as plasma
      testosterone (p<0.001) concentration were recorded compared to the controls. In
      rats on PND 280 fed a soy maintenance diet, the relative weights of all
      reproductive tissues were similar to those of controls, however, the weight of
      the body and the real weights of the reproductive tissues were lower (p<0.05)
      than in controls. The mean plasma concentrations of the reproductive hormones did
      not differ significantly between the two groups. In conclusion, a supplement of
      soy in the rat diet may affect growth and/or development of the reproductive
      tissues in male rats and also affect concentrations of reproductive hormones. The
      effects depend on the period of life when the soy diet is applied.

PMID- 17220954
TI  - New bradykinin analogues acylated on the N-terminus: effect on rat uterus and
      blood pressure.
AB  - Our previous studies suggested that acylation of the N-terminus of several known
      B2 antagonists with various kinds of bulky acyl groups consistently improved
      their antagonistic potency in rat blood pressure assay. On the other hand, our
      earlier observations also seemed to suggest that the effects of acylation on the
      contractility of isolated rat uterus depended substantially on the chemical
      character of the acyl group, as we observed that this modification might either
      change the range of antagonism or even transform it into agonism. Bearing all
      this in mind, we decided to synthesize seven new analogues of bradykinin by N
      terminal acylation with various acyl groups of a moderately potent B2 antagonist,
      previously synthesized by Stewart's group, D-Arg-Arg-Pro-Hyp-Gly-Thr-Ser-D-Phe
      Thi-Arg. The analogues were tested in vitro for their blood pressure-lowering and
      uterotonic activities. The modifications either preserved or increased the
      antagonistic potency in the rat blood pressure test. On the other hand, all seven
      substituents negatively influenced the interaction with the rat uterine
      receptors. Our results may be helpful for designing new B2 agonists and
      antagonists.

PMID- 17220955
TI  - Oxidative damage to DNA and antioxidant status in aging and age-related diseases.
AB  - Aging is a complex process involving morphologic and biochemical changes in
      single cells and in the whole organism. One of the most popular explanations of
      how aging occurs at the molecular level is the oxidative stress hypothesis.
      Oxidative stress leads in many cases to an age-dependent increase in the cellular
      level of oxidatively modified macromolecules including DNA, and it is this
      increase which has been linked to various pathological conditions, such as aging,
      carcinogenesis, neurodegenerative and cardiovascular diseases. It is, however,
      possible that a number of short-comings associated with gaps in our knowledge may
      be responsible for the failure to produce definite results when applied to
      understanding the role of DNA damage in aging and age-related diseases.

PMID- 17220956
TI  - Rho-kinase as a potential therapeutic target for the treatment of pulmonary
      hypertension.
AB  - Pulmonary hypertension (PH) is a cardiovascular disorder characterized by
      vasoconstriction and vascular remodeling. Recently, rapidly increasing evidence
      from various rat models of PH and patients with PH suggest that small GTPase Rho
      and its downstream effector, Rho-kinase, play a key role in the pathogenesis of
      PH. Activation of the Rho/Rho-kinase pathway is important for pulmonary
      endothelial dysfunction, pulmonary vascular smooth muscle cell contractility,
      proliferation and apoptosis in PH. A greater Rho-kinase expression and an
      enhanced Rho-kinase activity have been observed in pulmonary arteries of PH rats,
      such as hypoxia-induced, monocrotaline-induced and genetic spontaneous PH rats.
      Moreover, Y-27632 or fasudil, the selective Rho-kinase inhibitors, significantly
      attenuated PH in various pulmonary hypertensive model rats and patients with PH,
      but did not reduce systemic blood pressure. Therefore, Rho-kinase inhibitors may
      have therapeutic potential for the treatment of PH.

PMID- 17220957
TI  - Stroke biomarkers: Can they help us to guide stroke thrombolysis?
AB  - The use of blood biomarkers is getting increasingly popular in the field of
      cerebrovascular diseases, since biomarkers might aid physicians in several steps
      of stroke evaluation. We will discuss whether stroke diagnosis might be possible
      using some specific brain biomarkers and if this approach will permit rapid
      referral of stroke patients to hospitals with acute treatments such as tissue
      plasminogen activator (t-PA) available. Although thrombolytic therapy in acute
      stroke is effective since it accelerates clot lyses and earlier restoration of
      blood flow, up to 40-50% of treated patients do not recanalize or do it too late,
      and between 6 and 15% suffer hemorrhagic transformations with high death rates.
      In the context of the neurovascular unit, t-PA may degrade extracellular matrix
      integrity and increase risks of neurovascular cell death, blood-brain barrier
      leakage, edema and hemorrhage. In humans, biomarkers such as matrix
      metalloproteinase-9 (MMP-9) or fibronectin, which might be used to select
      patients at higher risk of hemorrhagic transformation, and high plasminogen
      activator inhibitor-1 (PAI-1) interfering with tPA-induced recanalization, thus
      predicting clot-lyses resistance and poor outcome, have been recently identified.
      Moreover, high levels of MMP-9 and MMP-13 are involved in DWI lesion growth in
      spite of thrombolytic therapy suggesting its ultra-early role in brain injury.
      Other biomarkers such as C-reactive protein may accurately predict stroke
      mortality following reperfusion therapies. Finally, we will also show that
      genetic background of stroke patients may condition plasma levels of some of
      these biomarkers and influence therapeutic response in t-PA-treated patients.

PMID- 17220958
TI  - Personalizing gene therapy in gastric cancer.
AB  - Gene therapy was proposed many decades ago as a more straightforward and
      definitive way of curing human diseases, but only recently technical advancements
      and improved knowledge have allowed its active development as a broad and
      promising research field. After the first successes in the cure of genetic and
      infectious diseases, it has been actively investigated as a means to decrease the
      burden and suffering generated by cancer. The field of gastric cancer is
      witnessing an impressive flourishing of studies testing the possibilities and
      actual efficacy of the many different strategies employed in gene therapy, and
      overall results seem to be two-sided: while original ideas and innovative
      protocols are providing extremely interesting contributions with great potential,
      more advanced-phase studies concluded so far have fallen short of expectations
      regarding efficacy, although invariably demonstrating little or no toxicity. An
      overview of the major efforts in this field is provided here, and a critical
      discussion is presented on the single strategies undertaken and on the overall
      balance between potentiality and pitfalls.

PMID- 17220959
TI  - Signaling mechanisms of axon growth inhibition.
AB  - Generally, the axons in the adult mammalian central nervous system (CNS) do not
      regenerate after injuries. This lack of regeneration results in partial
      disability or complete paralysis. To date, several axon growth inhibitors that
      are known to inhibit axon regeneration in the CNS have been identified in the
      myelin. Recent research has revealed the molecular mechanisms underlying the
      action of these inhibitors. RhoA and Rho-kinase--a downstream effector of RhoA-
      are key signals that elicit axon inhibition. These findings provide a number of
      promising strategies to promote axon regeneration after CNS injuries. Some
      strategies such as Rho/Rho-kinase inhibition have proved effective in animal
      models. Elucidation of the complete mechanism of the signal transduction will be
      useful for the development of efficient therapeutic strategies against injuries
      of the CNS.

PMID- 17220960
TI  - Potential therapeutic targets for idiopathic inflammatory myopathies.
AB  - The inflammatory myopathies essentially comprise three diseases with different
      immunopathologic features. Dermatomyositis (DM) is a complement-mediated
      microangiopathy. The immune response in polymyositis (PM) and sporadic inclusion
      body myositis (IBM) is a CD8+ T-cell-mediated cellular reaction against an
      unknown muscle fiber antigen. The multiple immune factors that guide inflammatory
      cell diapedesis and trafficking have been elucidated over the past two decades.
      Many of these molecules can now be targeted by monoclonal antibodies and other
      pharmacologic approaches. Randomized controlled trials are being started on a
      number of new agents to find out whether more specific immune interventions than
      the currently used glucocorticosteroids can treat DM and PM patients with fewer
      side effects, and may represent a first treatment modality for IBM, an entity
      unresponsive to all currently available pharmacological treatments.

PMID- 17220961
TI  - Clinical development of levetiracetam for amyotrophic lateral sclerosis.
AB  - This month's Spotlight on... focuses on the current clinical development of the
      antiepileptic drug levetiracetam for amyotrophic lateral sclerosis. We highlight
      the experimental rationale behind its progress into patient cohorts with regards
      to targeting three currently untreatable aspects of human amyotrophic lateral
      sclerosis: cramps, spasticity and disease progression.

PMID- 17220962
TI  - Molecule of the Month: Conivaptan hydrochloride.

PMID- 17220963
TI  - Systems biology: Potential to improve decision making in pharmaceutical
      development.
AB  - On October 5, 2006, the New England Systems Biology Association held its first
      annual meeting at Bentley College, Waltham, Massachusetts. The meeting was
      organized under the title "Systems Biology in Drug Discovery" and was devoted to
      the presentation of current status and advances in this new and ever-expanding
      field in medical sciences. It brought together biologists, biochemists,
      physicians, physicists and engineers, as well as leaders in biopharmaceutical
      industry interested in this field of science and its possible impact on
      anticancer drug discovery. The meeting consisted of two sessions, one in the
      morning and one in the afternoon and a panel discussion at noon. Each session
      hosted four speakers and a panel discussion featuring five discussants. Each
      session also included keynote speakers. Systems biology can help to identify
      disease-specific molecules and drug-specific targets. This is especially useful
      as a new tool in diagnostic approaches and drug discovery. Using specific
      techniques like gene profiling, marker detection and kinase-specific substrate
      definition, and combining them with large databases and computational methods it
      is possible to look at the organism as a complex association of gene activation
      and control networks, and their products, and thus gain better and more realistic
      insights into disease processes and into drug mechanisms.

PMID- 17220965
TI  - Molecular diversity through gold catalysis with alkynes.
AB  - In this feature article we cover most recent efforts in gold-catalysed
      transformations, highlighting the wide molecular diversity that can be achieved,
      in particular with regard to the formation of C-C bonds. Mechanistic
      interpretations of some cyclisations are based on our own work on the skeletal
      rearrangement of 1,6-enynes.

PMID- 17220964
TI  - Biomolecule-nanoparticle hybrids as functional units for nanobiotechnology.
AB  - Biomolecule-metal or semiconductor nanoparticle (NP) hybrid systems combine the
      recognition and catalytic properties of biomolecules with the unique electronic
      and optical properties of NPs. This enables the application of the hybrid systems
      in developing new electronic and optical biosensors, to synthesize nanowires and
      nanocircuits, and to fabricate new devices. Metal NPs are employed as nano
      connectors that activate redox enzymes, and they act as electrical or optical
      labels for biorecognition events. Similarly, semiconductor NPs act as optical
      probes for biorecognition processes. Double-stranded DNA or protein chains that
      are modified with metallic nanoclusters act as templates for the synthesis of
      metallic nanowires. The nanowires are used as building blocks to assemble nano
      devices such as a transistor or a nanotransporter.

PMID- 17220966
TI  - Increased crystal porosity and enhanced gas adsorption by intracolumnar gliding
      for broadband gas detection.
AB  - A new three-level structural approach based on anion-induced intracolumnar
      gliding of stacked coordinatively unsaturated units is described for design of
      metal-organic crystals which exhibit concentration- and gas-specific adsorption
      of a variety of small molecules and could be employed for multiple and rapid
      qualitative and quantitative broadband detection of gases or gaseous mixtures.

PMID- 17220967
TI  - A single-crystal imprints macroscopic orientation on xenon atoms.
AB  - A porous single-crystal collects xenon atoms from the gas phase and orients them
      macroscopically, as highlighted by hyperpolarized xenon NMR.

PMID- 17220968
TI  - Site-specific labeling of DNA-protein conjugates by means of expressed protein
      ligation.
AB  - Site-specific bioconjugation of protein thioesters with a DNA oligonucleotide was
      achieved by Expressed Protein Ligation (EPL) and the new thiol group formed upon
      EPL in the conjugate was selectively coupled with small molecule labels using
      maleimide chemistry.

PMID- 17220969
TI  - A trinucleating ligand based on 1,8-naphthalenediol: synthesis, structural and
      magnetic properties of a linear Cu(II)Cu(II)Cu(II) complex.
AB  - The extension of Robson-type ligands from dinucleating based on 2,6
      diformylphenol to trinucleating based on 2,7-diformyl-1,8-naphthalenediol is
      demonstrated by the synthesis, structural and magnetic characterization of the
      first trinuclear Cu(II) complex using a 1,8-naphthalenediol derived ligand.

PMID- 17220970
TI  - New insight into the mechanism of methyl transfer during the biosynthesis of
      fosfomycin.
AB  - Hydroxyethylphosphonate is a required intermediate in fosfomycin biosynthesis.

PMID- 17220972
TI  - Alternative donor substrates for inverting and retaining glycosyltransferases.
AB  - By the use of glycosyl donors containing aromatic leaving groups linked with
      opposite anomeric configurations compared to those of the natural donor
      substrates, an inverting (Cst II) and a retaining (LgtC) glycosyltransferase were
      found to catalyse glycosylation reactions of natural acceptor substrates in the
      presence of the corresponding nucleotide.

PMID- 17220971
TI  - Synthesis of well-defined Locust Bean Gum-graft-copolymers using ambient aqueous
      atom transfer radical polymerisation.
AB  - The first atom transfer radical graft copolymerisation at ambient temperature in
      water from a soluble polysaccharide is demonstrated for a range of monomer types.

PMID- 17220973
TI  - The first naturally occurring aromatic isothiocyanates, rapalexins A and B, are
      cruciferous phytoalexins.
AB  - The discovery of the first naturally occurring aromatic isothiocyanates, indole-3
      isothiocyanates, their first synthesis, antimicrobial activity and proposed
      biogenetic origin in canola plants are reported.

PMID- 17220974
TI  - Formation of left-handed helices in hybrid peptide oligomers with cis beta-sugar
      amino acid and L-Ala as building blocks.
AB  - Residue based control of specific helical folding is explored in hybrid peptide
      oligomers consisting of alternating L-Ala and cis-beta-furanoid sugar amino acid
      (FSAA) residues as building blocks; two series of these hybrid oligomers are
      designed, synthesized and extensively characterized by using NMR, CD, FT-IR and
      MD simulation studies; results show the co-existence of left-handed 11- and 14/15
      helical conformations in these short oligomers of Boc-(alpha/beta) and Boc
      (beta/alpha) series.

PMID- 17220975
TI  - Synthesis and characterization of difluoromethylene-homo[60]fullerene, C60(CF2).
AB  - Refluxing of the o-DCB solution of C60 with CF2ClCOONa and 18-crown-6 leads to
      formation of C60(CF2)n (n = 1-3); the monoadduct C60(CF2) has been found to
      consist of the main [6,6]- and minor [5,6]-isomers, both having an open
      structure.

PMID- 17220976
TI  - Characterizing the structure and dynamics of folded oligomers: Pulsed ESR studies
      of peptoid helices.
AB  - Helical peptoid oligomers were synthesized in which the positions of nitroxide
      radical spin probes along the backbone were systematically varied, allowing
      evaluation of intra-molecular distances and dynamics by electron spin resonance
      spectroscopy.

PMID- 17220977
TI  - Tri- and hexavalent mannoside clusters as potential inhibitors of type 1
      fimbriated bacteria using pentaerythritol and triazole linkages.
AB  - Several oligomannoside clusters having a hundred-fold increase in affinities
      toward E. coli were synthesized by Cu(I)-catalyzed [1,3]-dipolar cycloadditions
      using pentaerythritol scaffolds bearing either alkyne or azide functionalities.

PMID- 17220978
TI  - Towards improved gene delivery: Flip of cationic lipids in highly polarized
      liposomes.
AB  - Hyperpolarization of cationic liposomes improves their stability in the presence
      of human serum albumin.

PMID- 17220979
TI  - Magnetic Fe nanoparticle functionalized water-soluble multi-walled carbon
      nanotubules towards the preparation of sorbent for aromatic compounds removal.
AB  - Magnetic Fe nanoparticle functionalized water-soluble multi-walled carbon
      nanotubules (MWNTs) were prepared, characterized and used for the removal of
      aromatic compounds in water and re-use.

PMID- 17220980
TI  - Alpha-amino acid Troger base derivatives, possible conformationally restricted
      scaffolds?
AB  - The first synthesis of innovative alpha-amino acid conjugates of Troger base is
      reported; their potential application as conformationally restricted scaffolds is
      proposed and has been investigated using high level ab initio calculations.

PMID- 17220981
TI  - Chiral discrimination of alpha-amino acids by the DNA triplet GCA.
AB  - The DNA triplet GCA is successfully used for the first time as a chiral selector
      for the chiral discrimination and optical purity measurement of some alpha-amino
      acids by investigating the collision-induced dissociation spectra of the sodiated
      ternary complex ion formed by electrospray ionization.

PMID- 17220982
TI  - Tris(2,2'-bipyridyl)ruthenium(II) chemiluminescence enhanced by silver
      nanoparticles.
AB  - Mixtures of silver(I) and citrate that are used to produce silver nanoparticles
      evoke intense chemiluminescence with tris(2,2'-bipyridyl)ruthenium(II) and
      cerium(IV), which can be exploited for the determination of citrate ions and
      other analytes over a wide concentration range.

PMID- 17220983
TI  - One-pot preparation of coenzyme A analogues via an improved chemo-enzymatic
      synthesis of pre-CoA thioester synthons.
AB  - Coenzyme A analogues are synthesized in a one-pot preparation by
      biotransformation of pantothenate thioesters through the simultaneous use of
      three CoA biosynthetic enzymes, followed by aminolysis.

PMID- 17220984
TI  - An enzymatic method for site-specific labeling of recombinant proteins with
      oligonucleotides.
AB  - DNA was site-specifically conjugated to a substrate peptide of microbial
      transglutaminase fused to the N- or C-terminus of target proteins without the
      loss of the proteins' functions of interest.

PMID- 17220986
TI  - Unprecedented 3D entanglement of 1D zigzag coordination polymers leading to a
      robust microporous framework.
AB  - One-dimensional zigzag coordination chains in four different directions are
      hierarchically entangled to generate an unprecedented 3D interwoven framework,
      which exhibits permanent porosity and guest selectivity.

PMID- 17220985
TI  - Enzyme-quantum dots architecture for highly sensitive electrochemiluminescence
      biosensing of oxidase substrates.
AB  - A simple strategy for the fabrication of the first biosensor based on the
      intrinsic electrochemiluminescence of quantum dots coupled with an enzymatic
      reaction is proposed with glucose oxidase as a model, which could be applied in
      more bioanalytical systems for oxidase substrates.

PMID- 17220987
TI  - Vancomycin-induced morphological transformation of self-assembled amphiphilic
      diacetylene supramolecules.
AB  - Reversible ribbon-sphere microstructural transformation of dipeptide-containing
      diacetylene supramolecules was observed by specific ligand-receptor interactions.

PMID- 17220988
TI  - The P(bth)2- anion as a Janus head staple between lithium and manganese (bth =
      benzothiazol-2-yl, C7H4NS).
AB  - Deprotonation of HP(bth)2 (1) affords the lithium phosphanide [(Et2O)2Li(bth)2P],
      (2) with both nitrogen atoms coordinated to the lithium atom while in the
      heterobimetallic complex [Li(bth)2P{Mn(CO)2Cp}2](n) (3) additionally the
      phosphorus atom micro-bridges two Mn(CO)2Cp residues.

PMID- 17220989
TI  - Fluorescent CXCR4 chemokine receptor antagonists: metal activated binding.
AB  - The copper(II) complex of a novel rhodamine-azamacrocycle conjugate binds to the
      CXCR4 chemokine receptor and competes effectively against anti-CXCR4 monoclonal
      antibodies. The copper macrocycle unit adopts a trans-II configuration in the
      solid state.

PMID- 17220990
TI  - Development of a pharmaceutical cocrystal of a monophosphate salt with phosphoric
      acid.
AB  - We report the first case of a pharmaceutical cocrystal formed between an
      inorganic acid and an active pharmaceutical ingredient (API), which enabled us to
      develop a stable crystalline and bioavailable solid dosage form for
      pharmaceutical development where otherwise only unstable amorphous free form or
      salts could have been used.

PMID- 17220992
TI  - Preliminary evaluation of the endovascular treatment of intracranial aneurysms
      with detachable coils in vigil patients.
AB  - Endovascular treatment of intracranial aneurysms with coil embolization became
      the most important therapeutic option with better morbidity and mortality rates
      and quality of life. Following immobility, patients are treated with general
      anaesthesia. OBJECTIVE: To test viability of endovascular treatment on wake
      patients. METHOD: Considering clinical symptoms, psychological characteristics
      and aneurysmal morphology, four patients with five intracranial aneurysms were
      selected. RESULTS: Four among five cases were completed with this technique.
      Patient 1 was partially treated after 75 minutes presenting vesical stress.
      Patient 2 presented subarachnoid hemorrhage after aneurysmal re-rupture, and the
      procedure was completed under general anaesthesia. The other three patients
      presented no intercurrences during the treatment. CONCLUSION: Endovascular
      treatment on wake patients with intracranial aneurysm can be an alternative to a
      selected group of patients.

PMID- 17220991
TI  - Quantitative aspects of brain perfusion dynamic induced by BOLD fMRI.
AB  - The increase of relative cerebral blood flow (rCBF) may contribute for a change
      in blood oxygenation level dependent signal (BOLD). The main purpose of this
      study is to investigate some aspects of perfusional alterations in the human
      brain in response to a uniform stimulation: hypercapnia induced by breath
      holding. It was observed that the BOLD signal increased globally during
      hypercapnia and that it is correlated with the time of breath holding. This
      signal increase shows a clear distinction between gray and white matter, being
      greater in the grey matter.

PMID- 17220993
TI  - The role of the irritative zone and of the number and distribution of
      calcifications in the severity of epilepsy associated with intracranial
      calcifications.
AB  - OBJECTIVE: To determine the influence of the location of the irritative zone, and
      the number and the distribution of the intracranial calcifications in the
      severity of epilepsy associated with intracranial calcifications. METHOD: We
      studied 47 patients with epilepsy and intracranial calcifications, 24 with normal
      (Group A) and 23 with abnormal interictal EEGs (Group B), a control group (n=21)
      with abnormal interictal EEGs and normal CT-scans (Group C). Clinical,
      electroencephalographic and neuroradiological features were compared among
      groups. RESULTS: Temporal lobe interictal EEG abnormalities were found in 23/24
      Group B patients, and in all Group C patients. Most Group B and Group C patients
      presented temporal lobe seizure symptomatology, whereas in most Group A patients
      symptomatology was rolandic (p=0.0001). Epilepsy was more severe in Group B and
      Group C patients than in Group A patients (p=0.0001 and p=0.0054). No
      relationship was found between the number of calcifications and epilepsy
      severity. CONCLUSION: An irritative zone at the temporal lobe is more relevant in
      determining the severity, symptomatology and frequency of seizures than the
      number and location of calcifications.

PMID- 17220994
TI  - Residual signal auto-correlation to evaluate speech in Parkinson's disease
      patients.
AB  - OBJECTIVE: To evaluate the maximum residual signal auto-correlation also known as
      pitch amplitude (PA) values in patients with Parkinson's disease (PD) patients.
      METHOD: The signals of 21 Parkinson's patients were compared with 15 healthy
      individuals, divided according age and gender. RESULTS: Statistical difference
      was seen between groups for PA, 0.39 for controls and 0.25 for PD. Normal value
      threshold was set as 0.3; (p<0.001). In the Parkinson's group 80.77%, and in the
      control group only 12.28%, had a PA<0.3 demonstrating an association between
      these variables. The dispersion diagram for age and PA for PD individuals showed
      p=0.01 and r=0.54. There was no significant difference in relation to gender and
      PA between groups. CONCLUSION: The significant differences in pitchs amplitude
      between PD patients and healthy individuals demonstrate the methods specificity.
      The results showed the need of prospective controlled studies to improve the use
      and indications of residual signal auto-correlation to evaluate speech in PD
      patients.

PMID- 17220995
TI  - Central nervous system abnormalities on midline facial defects with hypertelorism
      detected by magnetic resonance image and computed tomography.
AB  - The aim of this study were to describe and to compare structural central nervous
      system (CNS) anomalies detected by magnetic resonance image (MRI) and computed
      tomography (CT) in individuals affected by midline facial defects with
      hypertelorism (MFDH) isolated or associated with multiple congenital anomalies
      (MCA). The investigation protocol included dysmorphological examination, skull
      and facial X-rays, brain CT and/or MRI. We studied 24 individuals, 12 of them had
      an isolated form (Group I) and the others, MCA with unknown etiology (Group II).
      There was no significative difference between Group I and II and the results are
      presented in set. In addition to the several CNS anomalies previously described,
      MRI (n=18) was useful for detection of neuronal migration errors. These data
      suggested that structural CNS anomalies and MFDH seem to have an intrinsic
      embryological relationship, which should be taken in account during the clinical
      follow-up.

PMID- 17220996
TI  - Growth status and academic performance in Brazilian school age children: growth
      retardation impairs mathematical, but not reading and spelling abilities.
AB  - AIM: To assess the effect of child growth status on academic achievement and the
      association between child growth and academic standing. METHOD: The heights of
      722 middle-school children were measured using standard procedures and height-for
      age z (HAZ) scores were calculated based on an international reference. Academic
      performance was assessed by an adaptation of the Wide Range Achievement Test
      (WRAT3) composed of Reading, Arithmetic and Spelling. RESULTS: Children in the
      group with higher HAZ scores performed better than children in the group with
      lower HAZ scores only on the Arithmetic subtest. This finding was confirmed by a
      multiple regression model analysis of the data. In addition, only performance on
      the Arithmetic subtest was positively associated with HAZ. CONCLUSION: These
      results indicate that growth retardation impacts specifically on the development
      of arithmetic (numeracy) skills and are consistent with a three-fold model of
      life course influences on health including latency, cumulative and pathway
      effects.

PMID- 17220997
TI  - Clinical assessment of language development in children at age 3 years that were
      born preterm.
AB  - OBJECTIVE: To evaluate the influence of gestational age and birth weight on
      language development and neurodevelopmental outcome at age 3 years in children
      born preterm. METHOD: Cross sectional study including 69 children followed in our
      developmental outpatient clinic. Patients were consecutively included at the time
      of the 3 years of age appointment and stratified for birth weight (<1500 grams
      and between 1500-2500 grams). All patients were assessed for receptive and
      expressive language , Denver II and Bayley II tests and clinical neurological
      examination. For analysis patients were divided in two groups normal language
      acquisition (NLA) and delay in language acquisition (DLA). RESULTS: NLA children
      had higher scores on mental and psychomotor (p=<0.01, p=0.012) indexes of Bayley
      II. Newborns with less than 1500 grams had lower scores on all Bayley scale at
      age 36 months (p=0.002, p=0.007 and p<0.001). Multivariate analysis suggests an
      association between gestational age (p=0.032), abnormal behavior (p<0.001) and
      delay in language acquisition. Denver test at 12 and 24 months of age was a good
      predictor of delayed receptive and expressive language at three years of age
      (p=<0.01 and p=<0.01). CONCLUSION: Children born prematurely with low birth
      weight had an increased risk of language acquisition delay, and those had also
      lower cognitive and behavior scores when compared to NLA.

PMID- 17220998
TI  - ECI-4 screening of attention deficit-hyperactivity disorder and co-morbidity in
      Mexican preschool children: preliminary results.
AB  - OBJECTIVE: To examine prospectively usefulness of Early Childhood Inventory-4
      (ECI-4) in identifying attention deficit-hyperactivity disorder (ADHD),
      oppositional defiant disorder (ODD), and conduct disorder (CD). METHOD: A sample
      of children <6 years of age were evaluated in school settings with ECI-4 and
      results compared with those of Conners Rating Scales-Revised (CRS-R) 6 months
      later. Sample consisted of 34 healthy children (20 boys, 14 girls) prospectively
      followed-up. RESULTS: Frequency of children fulfill DSM-IV AD-HD criteria in ECI
      4 parent scale was 17%, and in teacher scale was 32%. Frequency of children
      fulfill DSM-IV AD-HD criteria in parent CRS-R was 20%, and for teacher
      questionnaire was 23%. Correlations were significant among teacher ECI-4 and both
      teacher and parent CRS-R scales. Sensitivity and specificity of teacher and
      parent ECI-4 scales were not good. Frequency of ODD identified in parent ECI-4
      scale was 5%, and for teacher 17%. Frequency of ODD in CRS-R for parents and
      teachers questionnaires was 17%. CD was not identified by parents in ECI-4 scale,
      but in teacher scale frequency was 14%. CONCLUSION: These facts support partially
      the use of ECI-4 screening of ADHD in Spanish-speaking preschool children.

PMID- 17220999
TI  - Thinner abuse alters peak of frequency of EEG spectra analyses.
AB  - STUDY OBJECTIVE: The aim of the investigation was to use electroencephalography
      (EEG) to study whether long-term thinner abuse may result in the slowing,
      disorganization and asymmetry of the EEG cortical rhythms. METHOD: Twenty-two
      patients attending with antecedent of thinner abuse only, and twenty two controls
      without alcohol, smoking, and drug abuse in the same age range and gender were
      studied. EEG recording were compared by means of the analyses of peak of
      frequency (POF), frequency of disorganization, and asymmetry of the background
      activity in patients and controls at rest eyes-closed condition in electrodes P3,
      P4, O1, and O2. RESULTS: Significant differences in POF among groups was observed
      in P3 and P4 location showing lower values in thinner abusers, but not in O1 and
      O2 locations. Frequencies of disorganization and asymmetry showed significantly
      higher proportions in thinner abusers. Bivariate correlations among POF at the
      four electrode location and time of thinner abuse showed significant values.
      However after partial correlation calculation correcting for age, significant
      values disappeared. CONCLUSION: Thus thinner abuse relates with slowing of POF in
      the EEG of patients with thinner abuse associated with disorganization, and
      asymmetry depending on time of abuse.

PMID- 17221000
TI  - Alzheimer's disease in Brazilian elderly has a relation with homocysteine but not
      with MTHFR polymorphisms.
AB  - OBJECTIVE: To investigate the association between total plasma homocysteine
      concentration, C677T and A1298C polymorphisms in MTHFR gene and Alzheimer's
      disease (AD) development. METHOD: Forty-three patients with probable (63%) and
      possible (37%) AD and 50 non-demented controls were evaluated. Groups did not
      differ as to gender, age, scholar years, diabetes, alcohol and coffee intake and
      physical activity. Total plasma homocysteine (Hcy) levels were determined by HPLC
      and genotyping for MTHFR by PCR/RFLP. Mann-Whitney "U" test was used to compare
      quantitative variable, Fisher-Freeman-Halton test to compare genotypes and allele
      proportions and Chi-square test to other qualitative variables. RESULTS: AD
      patients presented higher total plasma Hcy levels than controls and the
      difference was statistically significant. No differences in the C677T and A1298C
      MTHFR polymorphisms distributions were found between patients and controls.
      Plasma homocysteine concentration did not change with MTHFR genotypes.
      CONCLUSION: Our data confirms the association between increased plasma Hcy
      concentration and AD and suggests that neither C677T nor A1298C MTHFR
      polymorphisms contributed to genetic susceptibility for AD in elderly individuals
      in the Northeast of Brazil.

PMID- 17221001
TI  - Absence of dementia in late-onset schizophrenia: a one year follow-up of a
      Brazilian case series.
AB  - BACKGROUND: Cognitive deficits of late-onset schizophrenia (LOS) patients have
      been reported as stable, although some prospective studies show that a sub-group
      develop a significant cognitive decline. Data on LOS from developing countries
      are scarce. OBJECTIVE: To evaluate the cognitive performance of Brazilian
      patients with LOS over the course of one year. METHOD: Thirteen LOS patients were
      evaluated at baseline and after one year with the Mini-Mental State Examination
      (MMSE), the CAMCOG, the Positive and Negative Symptoms Scale, the Pfeffers
      Activities of Daily Living (ADL), and the Neuropsychiatric Inventory (NPI).
      RESULTS: Cognition and activities of daily living remained stable over the course
      of one year [baseline MMSE= 21.31 (4.87) and CAMCOG=80.31 (16.68); end-point
      MMSE=20.77 (3.86) and CAMCOG=82.92 (14.42) (Z=-0.831; p=0.40); baseline ADL=4.31
      (5.65); end-point ADL= 5.92 (3.86) (Z=-0.831; p=0.40)]; end-point NPI=10.54
      (10.69) (Z=-0.737; p=0.46]. CONCLUSION: Like patients from developed countries,
      Brazilian patients with LOS do not seem to develop dementia, at least over the
      course of one year.

PMID- 17221002
TI  - Phobias, other psychiatric comorbidities and chronic migraine.
AB  - BACKGROUND: Comorbidity of chronic migraine (CM) with psychiatric disorders,
      mostly anxiety and mood disorders, is a well-recognized phenomenon. Phobias are
      one of the most common anxiety disorders in the general population. Phobias are
      more common in migraineurs than non-migraineurs. The clinical profile of phobias
      in CM has never been studied. METHOD: We investigated the psychiatric profile in
      56 patients with CM using the SCID I/P interview. RESULTS: Lifetime criteria for
      at least one mental disorder was found in 87.5% of the sample; 75% met criteria
      for at least one lifetime anxiety disorder and 60.7% of our sample fulfilled DSM
      IV criteria for lifetime phobic avoidant disorders. Mood and anxiety scores were
      higher in phobic patients than in non-phobic CM controls. Number of phobias
      correlated with higher levels of anxiety and depression. CONCLUSION: Phobias are
      common in CM. Its recognition may influence its management. Early treatment may
      lead to better prognosis.

PMID- 17221003
TI  - Prevalence and impact of headache and migraine among Pomeranians in Espirito
      Santo, Brazil.
AB  - This is the first study to assess the prevalence of headache and migraine among
      Pomeranian descendents in Brazil. A high prevalence of headache in the last 6
      months was found (53.2%). Most headache sufferers were diagnosed as having
      migraine (55%). More women reported to have headache than men (65% and 33.8%,
      respectively). Migraine was the most common headache found among women (62.2%).
      Among men migraine was responsible for only 37.8% of the cases of headache. A
      high impact of headache was found, especially among migraineurs. Most of the
      headache sufferers declared to seek medical assistance for headache (67%) and
      most of them used to take common analgesics for headache relief. None of them was
      under prophylactic therapy.

PMID- 17221004
TI  - Comparative analysis of multiple sleep latency tests (MSLT) parameters and
      occurrence of dreaming in patients with daytime sleepiness of narcoleptic and non
      narcoleptic origin.
AB  - OBJECTIVE: To compare MSLT parameters in two groups of patients with daytime
      sleepiness, correlated to the occurrence and onset of dreams. METHOD: Patients
      were submitted to the MSLT between January/1999 and June/2002. Sleep onset
      latency, REM sleep latency and total sleep time were determined. The occurrence
      of dreams was inquired following each MSLT series. Patients were classified as
      narcoleptic (N) or non-narcoleptic (NN). RESULTS: Thirty patients were studied,
      12 were classified as narcoleptics (N group; 40%), while the remaining 18 as non
      narcoleptic (NN group; 60%). Thirty MSLT were performed, resulting in 146 series.
      Sleep was detected in 126 series (86%) and dreams in 56 series (44.44%). Mean
      sleep time in the N group was 16.0+/-6.3 min, while 10.5+/-7.5 min in the NN
      group (p<0.0001). Mean sleep latency was 2.0+/-2.2 min and 7.2+/-6.0 min in the N
      and NN group, respectively (p<0.001). Mean REM sleep latency in the N group was
      3.2+/-3.1min and 6.9+/-3.7 min in the NN group (p=0.021). Dreams occurred in
      56.9% of the N group series and 28.4% in that of the NN group (p=0.0009). Dream
      frequency was detected in 29.8% and 75% of the NREM series of the N and NN
      groups, respectively (p=0.0001). CONCLUSION: Patients from the N group, compared
      to the NN group, slept longer and earlier, demonstrated a shorter REM sleep onset
      and greater dream frequency. NN patients had a greater dream frequency in NREM
      series. Thus, the occurrence of dreams during NREM in the MSLT may contribute to
      differentially diagnose narcolepsy and daytime sleepiness.

PMID- 17221005
TI  - Strategies for resection of lesions in the motor area: preliminary results in 42
      surgical patients.
AB  - In recent years considerable technological advances have been made with the
      purpose of improving the surgical results in the treatment of eloquent lesions.
      The overall aim of this study is to evaluate the postoperative surgical outcome
      in 42 patients who underwent surgery to remove lesions around the motor cortex,
      in which preoperative planning by using neuroimaging exams, anatomical study,
      appropriate microsurgery technique and auxiliary methods such as cortical
      stimulation were performed. Twenty-two patients (52.3%) presented a normal motor
      function in the preoperative period. Of these, six developed transitory deficit.
      Twenty patients (47.6%) had a motor deficit preoperatively, nevertheless 90% of
      these improved postoperatively. Surgery in the motor area becomes safer and more
      effective with preoperative localization exams, anatomical knowledge and
      appropriate microsurgery technique. Cortical stimulation is important because it
      made possible to maximize the resection reducing the risk of a motor deficit.
      Stereotaxy method was useful in the location of subcortical lesions.

PMID- 17221006
TI  - Intrasellar pressure and tumor volume in pituitary tumor: relation study.
AB  - OBJECTIVE: To determine if there was a relationship between intrassellar pressure
      (ISP) and pituitary tumor volume. METHOD: Between August 2002 and May 2004, 60
      patients aged between 13 and 75 years old (39 males), having a pituitary adenoma
      were submitted to an endoscope transseptal approach. During the surgery and
      before tumor resection, 2 mm of the sellas floor were removed and a 1.5 mm dural
      opening made to place a transducer into the pituitary adenoma. The transducer was
      connected to a pressure monitor. RESULTS: The intrasellar pressure, ranged from 2
      51 mmHg and was measured based on the classification of Hardy-Vezina. The most
      elevated was in the type II macro adenomas with 32.6 mmHg, sharply superior to
      the value of a normal intracranial pressure. CONCLUSION: These values showed that
      the macroadenomas confined to the sella, without destruction of the floor and
      integrity of the diaphragm, type II of Hardy-Vezina, presented a value of ISP
      much higher than intra-extrasellar macroadenoma's.

PMID- 17221007
TI  - Primary lymphoma of the central nervous system: a clinical-pathological and
      immunohistochemical study of ten autopsy cases.
AB  - CONTEXT: Primary central nervous system lymphomas (PCNSL) are a rare subgroup of
      lymphomas generally associated with HIV and EBV. OBJECTIVE: To study ten autopsy
      cases of PCNSL, to describe the neuropathological findings, to characterize the
      phenotype of the neoplastic cells, to detect EBV in the lesion and to compare the
      findings with the clinical and laboratory data of the patients. METHOD: The
      clinical, histological and immunohistochemical data of ten cases of PCNSL, eight
      cases from patients with AIDS, identified among 265 autopsies of these patients
      were analyzed. RESULTS: Seven patients were males and the mean age was 40.9
      years. The most frequent symptomatology was focal neurologic deficit (70%). Six
      patients presented with only one lesion. Histologically, densely cellular and
      polymorphous neoplasms with angiocentrism were observed, in 90% of cases. An
      association with other diseases was observed in four cases. Most patients had
      diffuse large B cell non-Hodgkins lymphoma. EBV was detected by
      immunohistochemistry in only one case. The lack of detection of the virus might
      have been due to the long time of fixation of the brain which might have
      inactivate epitopes therefore compromising the testing. CONCLUSION: In the
      present series, PCNSL presented with focal symptoms, with unifocal or multifocal
      lesions, with a predominant B-cell CD20 positive phenotype, rarely associated
      with EBV.

PMID- 17221008
TI  - Percutaneous radiofrequency rhizotomy and neurovascular decompression of the
      trigeminal nerve for the treatment of facial pain.
AB  - OBJECTIVE: To determine the outcomes of 354 radiofrequency rhizotomies and 21
      neurovascular decompressions performed as treatment for 367 facial pain patients
      (290 idiopathic trigeminal neuralgia, 52 symptomatic trigeminal neuralgia, 16
      atypical facial pain, 9 post-herpetic neuralgia). METHOD: Clinical findings and
      surgery success rate were considered for evaluation. A scale of success rate was
      determined to classify patients, which considered pain relief and
      functional/sensorial deficits. RESULTS: Radiofrequency rhizotomy was performed in
      273 patients with idiopathic trigeminal neuralgia and in all other patients,
      except for trigeminal neuropathy; neurovascular decompression was performed in 18
      idiopathic trigeminal neuralgia patients; 100% idiopathic trigeminal neuralgia,
      96.2% symptomatic trigeminal neuralgia, 37.5% atypical facial pain and 88.9% post
      herpetic neuralgia had pain relief. CONCLUSION: Both techniques for idiopathic
      trigeminal neuralgia are usefull. Radiofrequency rhizotomy was also efficient to
      treat symptomatic facial pain, and post-herpetic facial pain, but is not a good
      technique for atypical facial pain.

PMID- 17221009
TI  - [Neonatal treatment effect with selective inhibitor of 5-HT recapture on
      [corrected] the cranium-encephalic anatomic development].
AB  - Neonatal repercussion researched of the serotonin selective recapture inibitor
      (SSRI) chronic treatment about the somatic growth, of the encephalon and skull.
      Male rats were divided into groups: control (NaCl) and Cit (10 microL/Kg
      citalopram 10 mg). In 21 post birth days were measured body weight, side axle ,
      front and rear and skull circle. At 8, 15, 22 days after birth, animals were
      sacrified for the encephalon withdrawal to evaluate the measurements mentioned
      above. SSRI use caused body growth deficit, skull and encephalon reduction. The
      retard is possibly caused by the magnitude change of the trophic serotonin action
      over the skull-facial morphogenesis, reinforcing the serotoninergic system
      participation over the somatic and ontogenic growth. The SSRI possible hypophagic
      effects are not discarded.

PMID- 17221010
TI  - [Traumatic brain injury in children and adolescents at Salvador City, Bahia,
      Brazil].
AB  - OBJECTIVE: To verify the frequency of traumatic brain injury (TBI) in the people
      between 0 and 19 years of age, in accordance to gender, age and cause of trauma.
      METHOD: Descriptive study made through a period of a year, in all TBI victims,
      aged until 19 years admitted in a reference trauma center. RESULTS: The sample
      had a total of 390 patients; 280 (71.8%) were boys. The main age of the victims
      was between 10 to 19 years (adolescents) with 177 patients (45.4%). The most
      common cause of trauma was height falls (34.4%). According to the Glasgow Coma
      Scale, 89% had suffered mild TBI. CONCLUSION: The main group of victims was the
      adolescents; the most important cause of TBI was height fall, with masculine
      predominance and mild trauma.

PMID- 17221011
TI  - [Pain and numbness in the arms and hands and carpal tunnel syndrome diagnosis].
AB  - We studied the frequency and localization of pain and numbness in patients with
      carpal tunnel syndrome (CTS), in comparison with individuals of the general
      population, matched for sex and age, and we determined the sensitivity and the
      specificity of these symptoms for the CTS diagnosis. Pain was a common symptom in
      the two groups of patients. Numbness occurred more frequently in CTS group
      (p<0.05). In CTS patients, pain complaints were present in neck (42.8%), arms
      (36.8%) and hands (82.8%). Among controls, pain was more common in head (11.4%),
      trunk (37.1%), legs (22.8%). In our casuistics, in relation to the CTS diagnosis,
      the presence of pain and numbness have low sensitivity and high specificity when
      they occur in the arms, and high sensitivity and specificity when they occur in
      the hands.

PMID- 17221012
TI  - [Management of deep wound infections in spinal lumbar fusions].
AB  - The rate of deep wound infections in spinal lumbar fusions is around 0.7% to
      11.6%, being one of the causes of morbidity in acute phase. The aim of this study
      was to evaluate the management of spinal infection after internal lumbar fusions.
      Two hundred and sixty patients, who underwent to spinal surgery with lumbar
      fusion and iliac bone grafting, were analized, from January 1997 to January 2005.
      Wound infection was observed in eight (3%) cases. The average of age was 56
      years, with a higher prevalence in males (5 patients). Most prevalent was
      Staphylococcus aureus in 6 patients. The treatment was done by intravenous
      antibiotic therapy folowed by oral therapy and local irrigation. The average time
      of hospitalization was 35.8 days. It was possible to erradicate infection without
      removal of instrumentation in all patients.

PMID- 17221013
TI  - [Comparison of intravenous dipyrone to intravenous metoclopramide in the
      treatment of acute crisis of migraine: randomized clinical trial].
AB  - INTRODUCTION: Migraine is one of the commonest diseases of clinical practice.
      OBJECTIVE: [corrected] To compare the analgesic effect of dipyrone to
      metoclopramide in the relief of pain. METHOD: We conducted a pilot randomized
      study comparing intravenous dipyrone to intravenous metoclopramide in 27 patients
      presenting acute crisis of migraine. The primary end point was to compare
      reduction of intensity of pain up to 2 hours, as well as the development of
      collateral effects. RESULTS: The groups had similar ages, but there were
      difference between the sexes. In men, metoclopramide reduced pain in 80.0%
      compared with 55.0% from dipyrone (p=0.052). In women, there was a reduction of
      65.0% with metoclopramide and 71.2% with dipyrone (p=0.748). The small number of
      patients in the study might have influenced these results. Significant collateral
      effects were not found. CONCLUSION: There was no difference about the intensity
      of pain reduction neither about the development of collateral effects comparing
      dipyrone to metoclopramide.

PMID- 17221014
TI  - [Relation between clinical evaluation of deglutition and the computed tomography
      in acute ischemic stroke patients].
AB  - Stroke is one of the main causes of permanent lesions in adults and can provoke
      global motor sequels, speech and language alterations, and swallowing. During the
      acute phase, the detection of aspiration risks is essential to prevent lung
      complications and to allow appropriate therapeutic interventions, making possible
      precocious oral feeding. In the literature, the correlations between the
      disturbance of the deglutition and the location of the lesion in patients with
      stroke are not specific. This way, the objective of the present study was to
      determine if correlation exists between the location of the vascular lesion and
      dysphagia in acute ischemic stroke patients. Bedside clinical evaluation of
      deglutition was made in 27 patients with acute ischemic stroke and the results
      were compared with the computed tomography findings. In the clinical evaluation,
      48% patients were dysphagic and 52% had functional deglutition. In dysphagic
      patients, 84% had lesion in carotid territory, with 76% in the middle cerebral
      artery. In patients with functional deglutition, 57% had lesion in the middle
      cerebral artery and 22% in the posterior cerebral artery. In 50% of the patients
      with functional deglutition and in 46% of the dysphagics the lesion was in the
      left hemisphere. In conclusion, the hemispherical location is not associated with
      the presence or not of dysphagia, however most of the dysphagic patients
      presented alterations in the carotid territory, especially in the middle cerebral
      artery.

PMID- 17221015
TI  - Central neurocytomas of uncommon locations: report of two cases.
AB  - We report two patients with central neurocytomas at an uncommon location in the
      brain. The first, a 58-year-old man presenting with signs and symptoms of
      increased intracranial pressure, had a tumor located at the pineal region. The
      second, a 21-year-old woman with tumor in the aqueductal region had worsening
      migraine-like headaches and diplopia. Both patients had obstructive hydrocephalus
      treated by neuroendoscopic third ventriculostomy and biopsy of the tumors. No
      additional treatment was done. We conclude that neurocytomas should be considered
      in the differential diagnosis of tumors located in the pineal and aqueductal
      regions.

PMID- 17221016
TI  - Dopamine dysregulation syndrome in Parkinson's disease: case report.
AB  - We report a 67-year-old man with Parkinson's disease for 9 years who developed
      compulsive use of levodopa. This phenomenon is the main feature of the dopamine
      dysregulation syndrome. Other related symptoms presented by our patient were mood
      fluctuation and increased writing activity suggestive of punding.

PMID- 17221017
TI  - Lissencephaly, abnormal genitalia and refractory epilepsy: case report of XLAG
      syndrome.
AB  - INTRODUCTION: X-linked lissencephaly with ambiguous genitalia (XLAG) is a
      recently described genetic disorder caused by mutation in the aristaless-related
      homeobox (ARX) gene (Xp22.13). Patients present with lissencephaly, agenesis of
      the corpus callosum, refractory epilepsy of neonatal onset, acquired microcephaly
      and male genotype with ambiguous genitalia. CASE REPORT: Second child born to
      healthy nonconsanguineous parents, presented with seizures within the first hour
      of life that remained refractory to phenobarbital, phenytoin and midazolam.
      Examination identified microcephaly, axial hypotonia, pyramidal signs and
      ambiguous genitalia. EEG showed disorganized background activity and seizures
      starting at the right midtemporal, central and occipital regions. MRI showed
      diffuse pachygyria, moderate thickening of the cortex, enlarged ventricles,
      agenesis of the corpus callosum and septum pellucidum. Karyotype showed a 46,XY
      genotype. Additional findings were hypercalciuria, vesicoureteral reflux, patent
      ductus arteriosus and chronic diarrhea.

PMID- 17221019
TI  - Fatal intracerebral hemorrhage secondary to Lonomia obliqua caterpillar
      envenoming: case report.
AB  - The case of a 70 year-old, previously healthy woman who developed a severe
      bleeding diathesis shortly after touching a Lonomia obliqua caterpillar and
      finally died from multiple intracerebral hemorrhages is described. Brain
      hemorrhages are the leading cause of death in patients envenomed by the Lonomia
      species. The pertinent literature is reviewed and the most relevant clinical
      features highlighted, with emphasis on diagnosis. The use of new therapeutic
      options such as anti-Lonomia serum is discussed.

PMID- 17221018
TI  - Botulinum-A toxin in the treatment of painful post-stroke nocturnal paroxysmal
      dystonia triggered by periodic limb movements of sleep: case report.
AB  - INTRODUCTION: Sleep disorders presenting involuntary movements may be very
      annoying to patients, apart from their negative influence on sleep. OBJECTIVE: To
      report the use of botulinum type-A toxin (BoNT-A) to manage the case of a patient
      whose sleep was severely disrupted by episodes of dystonic posturing of the right
      lower limb triggered by periodic limb movements of sleep (PLMS). METHOD: A 79
      year-old woman with mild post-stroke right hemiparesis presented with recurrent
      painful episodes of dystonia of the right lower limb, which disrupted her sleep.
      The dystonic episodes could also be voluntarily triggered by extension of the
      right hallux. Polysomnography confirmed that the dystonic episodes were triggered
      by PLMS. Twenty units of BoNT-A (20U/500U vial) were injected into her right
      extensor hallucis longus. RESULTS: Shortly after BoNT-A was injected, the
      dystonic symptoms abated, and the patient achieved better sleep efficiency.
      CONCLUSION: The PLMS-related involuntary extension of the hallux was probably
      triggering the nocturnal post-stroke lower limb dystonic paroxysms. BoNT-A
      injection into the right extensor hallucis longus was effective in managing this
      condition and thus resolved the associated disruption of sleep.

PMID- 17221020
TI  - Cerebral X-linked adrenoleukodystrophy: follow-up with magnetic resonance
      imaging.
AB  - OBJECTIVE: To report a case of childhood cerebral X-linked adrenoleukodystrophy
      (X-ADL), emphasizing the magnetic resonance imaging (MRI) findings at initial
      evaluation and at the follow-up. CASE REPORT: Five year-old boy, who was
      asymptomatic, presented with diagnosis of X-ADL for MRI evaluation. The initial
      brain MRI showed a focal area of enhancement at the splenium of the corpus
      calosum. One year later, the follow-up MRI showed a progression of the corpus
      calosus lesion, as well as other lesions in the parietal and occipital lobes.
      CONCLUSION: The brain MRI follow-up of patients with X-ADL is important to show
      the progression of the lesions.

PMID- 17221021
TI  - Intoxication with oral hypoglycemics as a cause of diffuse brain injury: case
      report.
AB  - OBJECTIVE: To present the imaging findings of a patient with diffuse brain injury
      secondary to intoxication with oral hypoglycemics. CASE REPORT: A nine years-old
      boy presented with generalized tonic-clonic convulsions and decreased
      consciousness. Laboratory investigation demonstrated blood glucose level of 21
      mg/dL. The magnetic resonance imaging showed cortical and subcortical temporo
      parieto-occipital areas of high signal on T2 and low signal on T1, with high
      signal on the diffusion-weighted images and low signal on apparent diffusion
      coefficient maps. CONCLUSION: Cortical and subcortical temporal, parietal and
      occipital ischemic lesions may be seen in patients with intoxication by oral
      hypoglycemics.

PMID- 17221022
TI  - Guillain-Barre syndrome after brachial plexus trauma: case report.
AB  - The Guilllain-Barre syndrome (GBS) is an acute predominantly demyelinating
      polyneuropathy. In many cases GBS is preceding by infection, immunization,
      surgery or trauma. Although there are a few reports of GBS after head trauma,
      there is no report of this syndrome after brachial plexus injury. We report on a
      51 years-old man who presented GBS fifteen days after a brachial plexus trauma.
      The polineuropathy resolved completely in a few weeks. We believe that GBS was
      triggered by the trauma that evoked an immune mediated disorder producing
      inflammation and demyelination of the peripheral nerves.

PMID- 17221023
TI  - Cerebral venous thrombosis and hepatitis: case report.
AB  - Among the many infective causes of cerebral venous thrombosis (CVT), viral
      hepatitis is been regarded as a rare associated condition. We report on a 56
      years-old man presenting CVT associated with hepatitis B and C coinfections
      outlining probable pathogenic mechanisms. We suggest that virus B and C serology
      should be performed in the cases of cerebral venous thrombosis with unknown
      etiology.

PMID- 17221024
TI  - [Primary amebic meningoencephalitis: two new cases report from Venezuela].
AB  - Primary amebic menigoencephalitis (PAM) is rare. Two cases of PAM in Venezuelan
      patients are described. Case 1, a 10 year-old male with headache, fever,
      vomiting. The patient swam in a water reservoir before the onset of his disease.
      He died during his third hospital day. Case 2, a 23 year-old male with a history
      of headache, fever, vomiting, drowsiness, and behavioral disturbances. The
      patient died on his second hospital day. The diagnosis in both cases was PAM due
      to Naegleria fowleri. Central nervous system infection by free-living amebas
      should be considered in meningoencephalitides with bacterial-free cerebro-spinal
      fluid.

PMID- 17221025
TI  - [Spontaneous internal carotid artery dissection with paralysis of lower cranial
      nerves: case report].
AB  - Spontaneous internal carotid artery dissection is a rare event that strikes
      patients at their productive age. As early intervention frequently determines a
      significant improvement, it is important to broaden the knowledge of the
      clinical, pathogenic and pathophysiological aspects of this disease. The
      objective is making an early diagnosis and treatment to avoid a bad outcome. We
      report the case of a 46 years-old man with spontaneous carotid artery dissection
      that had an atypical manifestation characterized by sudden paralysis of lower
      cranial nerves.

PMID- 17221026
TI  - Basilar impression associated with impacted cisterna magna, spastic paraparesis
      and distress of balance.

PMID- 17221028
TI  - Evaluation of coronary stent by cardiac computed tomography.

PMID- 17221029
TI  - Periodontal disease as a potential risk factor for acute coronary syndromes.

PMID- 17221030
TI  - The signal-averaged electrocardiogram of atrial activation in patients with or
      without paroxysmal atrial fibrillation.
AB  - OBJECTIVE: To analyze the parameters of the time domain P-wave signal-averaged
      electrocardiogram (P-SAECG) and compare them with the P-wave duration on the
      conventional electrocardiogram (P on ECG) as well as the left atrium diameter
      (LAD) and left ventricular ejection fraction (EF) obtained on the echocardiogram
      in order to evaluate patients with paroxysmal atrial fibrillation (PAF). METHODS:
      One hundred and eighty-one patients were included in the study: 117 with
      confirmed PAF and 64 without PAF. The P-SAECG parameters used were: the filtered
      P-wave duration (FPD), the root mean square (RMS) voltages in the last 40, 30 and
      20 ms of the filtered P-wave (RMS 40, RMS 30 and RMS 20), the root mean square
      voltage of the filtered P-wave potentials (RMS P), the integral of the potentials
      during the filtered P-wave (Integral P) and the filtered P-wave late potential
      durations below 3 microV (PL<3). RESULTS: The parameters that presented
      significant statistical differences between the groups were: FPD, RMS 40, 30 and
      20, PL<3, P on ECG and LAD. The ROC curve calculations demonstrated the best cut
      off points and performance estimates for each parameter: sensitivity,
      specificity, area under the curve and p-value (p). CONCLUSION: The time domain P
      SAECG proved to be a superior method to identify patients with paroxysmal atrial
      fibrillation than the conventional electrocardiogram and echocardiogram.

PMID- 17221031
TI  - Syncope in patients with right ventricle outflow tract premature beats and no
      apparent structural cardiopathy.
AB  - OBJECTIVE: Study the prevalence of neurocardiogenic etiology in patients with
      unexplained syncope and ventricular premature beats, with right ventricle outflow
      tract morphology (RVOT) and no apparent structural cardiopathy. METHODS: Ninety
      patients (66 women, mean age 40.2 +/- 16.95 years of age) with monomorphic
      premature beats originated at RVOT were evaluated prospectively. Fifty-four
      patients reported syncopes or near-syncopes associated to palpitations or not;
      twenty-seven presented palpitations with no pre-syncope or syncope, and nine were
      asymptomatic. All patients were submitted to echocardiogram, high resolution ECG
      and cardiac MRI to rule out structural cardiopathy, to exertion test to rule out
      adrenergic dependent ventricular tachycardia, and ECG prolonged outpatient
      monitoring (Holter and symptomatic events monitor) to correlate symptoms and
      ventricular arrhythmias. Investigation on the susceptibility to neurocardiogenic
      syncope was evaluated by Tilt Table Test (TTT). Groups were compared regarding
      gender, age, premature beats frequency and complexity, at exertion or not, TTT
      results and clinical course. RESULTS: In the syncope and pre-syncope groups, TTT
      was positive for 38% of cases, and in groups with palpitations and
      assymptomatics, it was positive for 11% (p = 0.0257). After recommendations and
      treatment of neurocardiogenic syncope, 85% of syncope and pre-syncope patients
      and positive TTT was asymptomatic along the 40-month follow-up. Two patients with
      syncope and negative TTT presented spontaneous, sustained ventricular tachycardia
      during clinic course. CONCLUSION: The prevalence of neurocardiogenic syncope in
      patients with idiopathic RVOT premature beats is high. Patients with recurrent,
      unexplained syncope and idiopathic VE must be kept under investigation.

PMID- 17221032
TI  - Late outcome of sirolimus-eluting stents: comparison of multidetector computed
      tomography with quantitative coronary angiography and intravascular ultrasound.
AB  - OBJECTIVE: To assess the performance of multidetector computed tomography in
      determining late clinical outcomes of patients undergoing sirolimus-eluting stent
      implantation. METHODS: Thirty patients, successfully submitted to sirolimus
      eluting stent implantation for more than six months, were selected to participate
      in the study. All underwent invasive angiography and intravascular ultrasound
      following CT angiography using iodinated contrast medium at a dose of 1.5 ml/kg.
      RESULTS: Mean proximal reference diameter was 3.01 +/- 0.31 mm by tomography and
      3.14 +/- 0.31 mm by angiography (p = 0.04). When the left circumflex artery was
      excluded from the analysis, the difference between both examinations was no
      longer significant (tomography = 3.01 +/- 0.32 mm; angiography = 3.10 +/- 0.30
      mm, p = 0.65). Mean distal reference diameter was 2.86 +/- 0.30 mm by tomography
      and 2.92 +/- 0.32 by angiography (p = 0.25). Mean in-stent minimal lumen diameter
      was 2.85 +/- 0.25 mm by tomography and 2.85 +/- 0.29 mm by angiography (p =
      0.27). Mean minimal in-stent cross-sectional area was 7.19 +/- 1.47 mm(2) by
      tomography and 6.90 +/- 1.52 mm(2) by intravascular ultrasound (p = 0.36), but
      there was only a weak correlation between these measurements (r = 0.33).
      CONCLUSION: Computed tomography allows the qualitative assessment of sirolimus
      eluting stents, accurate estimate of proximal and distal reference diameters of
      the target vessel, and in-stent minimal lumen diameter. Its correlation with
      measurements performed using intravascular ultrasound, however, is less strong.

PMID- 17221033
TI  - Ten-year experience with the Ross operation.
AB  - OBJECTIVE: To evaluate the 10-year outcomes of the Ross Operation, analyzing
      survival rate, incidence of reoperations, and late performance of pulmonary
      autografts and homografts in the reconstruction of the right ventricular outflow
      tract. METHODS: Two hundred and twenty seven patients with a mean age of 29.1 +/-
      11 years underwent Ross operation from May 1995 to February 2005. The most
      prevalent etiology was rheumatic disease in 61% of the cases. Autografts were
      implanted using the total root replacement technique in 202 cases, with
      intraluminal cylinder in 20, and in the subcoronary position in 5. The right
      ventricular outflow tract was conventionally reconstructed with cryopreserved
      homografts (n = 160), with proximal extension of the homograft with pericardium
      (n = 41), and with decellularized homografts (n = 26). The postoperative follow
      up ranged from 1 to 118 months (mean = 45.5 months). RESULTS: Hospital mortality
      was 3.5%, and long-term survival was 96.9% at ten years. No episodes of
      thromboembolism and only two cases of endocarditis occurred. Eleven patients
      underwent reoperation because of problems related to the auto and/or homograft,
      progression of rheumatic mitral valve disease, and iatrogenic coronary
      insufficiency. After 10 years, 96.4% and 96.2% of the patients were free from
      reoperation in the autograft and homograft groups, respectively. No late
      autograft dilatation was observed. Reconstruction of the left ventricular outflow
      tract with decellularized homografts significantly reduced the incidence of
      gradients on late follow-up. CONCLUSION: Late outcomes with the Ross Operation
      were associated with an excellent long-term survival and a low incidence of
      reoperations and late morbidity. We consider this procedure the best option for
      the surgical treatment of aortic valve disease in children and young adults.

PMID- 17221034
TI  - Periodontal disease as a potential risk factor for acute coronary syndromes.
AB  - OBJECTIVE: To investigate whether there is a relationship between active
      periodontal disease (PD) and acute coronary syndromes (ACS). METHODS: Three
      hundred and sixty-one patients (57,3% male), ages ranging from 27 to 89 (mean +/-
      DP = 60.5 +/- 12.2), were admitted to the Intensive Care Unit of a Teaching
      Hospital with symptoms and complementary examinations consistent with acute
      coronary syndrome. All the patients had a complete periodontal examination in the
      ICU setting, and 325 (90.9%) underwent coronary angiography for diagnostic
      confirmation and/or treatment planning. Periodontal examination included
      evaluation of all the teeth in the oral cavity and the following parameters:
      probing depth, clinical attachment level, plaque index, and gingival index.
      RESULTS: Of the 325 patients, 91 (28%) had coronary arteries free of obstruction
      or with mild obstructions (< 50% diameter stenosis), and the remaining 72% had
      severe obstructions. Fisher's exact text yielded a p value of 0.0245 with an odds
      ratio of 2.571 (95% CI 1.192 to 5.547), meaning that the group with ACS and
      significant obstructive coronary artery disease was 2.5-fold more likely to have
      active PD. CONCLUSION: A significant association was found between active
      periodontal disease and severe obstructive coronary artery in patients with acute
      coronary syndrome, underscoring the importance of prevention and adequate
      treatment of periodontal disease, which should be considered as a potential risk
      factor in the etiology and instability of the atherosclerotic plaque.

PMID- 17221035
TI  - Acute coronary syndrome registry at a cardiology emergency center.
AB  - OBJECTIVE: Describe clinical characteristics of patients (P) admitted to hospital
      with suspected acute coronary syndrome (ACS), identifying medical treatment and
      in-hospital mortality. METHODS: Evaluated were 860 patients with ACS from January
      through December, 2003. We evaluated baseline characteristics, ACS mode of
      presentation, medication during hospital stay, indication for clinical treatment
      or myocardial revascularization (MR) and in-hospital mortality. RESULTS: Five
      hundred and three (58.3%) were male, mean age 62.6 years ( +/- 11.9). Seventy
      eight (9.1%) were discharged with the diagnosis of acute ST-elevation myocardial
      infarction (STEMI), 238 (27.7%) with non-ST-elevation myocardial infarction (non
      STEMI), 516 (60%) with unstable angina (UA), two (0.2%) with atypical
      manifestations of ACS and 26 (3%) with non-cardiac chest pain. During
      hospitalization, 87.9% of patients were given a beta-blocker, 95.9%
      acetylsalicylic acid, 89.9% anti-thrombin therapy, 86.2% intravenous
      nitroglycerin, 6.4% glycoprotein (GP) IIb/IIIa receptor inhibitor, 35.9%
      clopidogrel, 77.9% angiotensin-converting enzyme inhibitor, and 70,9% statin
      drugs. Coronary arteriography was performed in 72 patients (92.3%) with STEMI,
      and in 452 (59.8%) with non-STEMI ACS (p< 0.0001). Myocardial revascularization
      (MR) surgery was indicated for 12.9% and percutaneous coronary intervention for
      26.6%. In-hospital mortality was 4.8%, and no difference was recorded between the
      proportion of deaths among patients with STEMI and non-STEMI ACS (6.4% versus
      4.8%; p = 0.578). CONCLUSION: In this registry, we provide a description of ACS
      patient, which allows the evaluation of the demographic characteristics, medical
      treatment prescribed, and in-hospital mortality. A greater awareness of our
      reality may help the medical community to adhere more strictly to the procedures
      set by guidelines.

PMID- 17221036
TI  - Clonidine in cineangiocardiography: sedative effects on blood pressure and heart
      rate.
AB  - OBJECTIVE: To evaluate the effects of clonidine on heart rate (HR), and blood
      pressure (BP) as well as its sedative effect on patients submitted to a
      cineangiocardiography. METHODS: A randomized, controlled, double blind,
      prospective clinical trial was conducted on 62 patients submitted to an elective
      cineangiocardiography. The patients were divided in two groups: the clonidine
      group, that were administered a 0.8 microg/kg dose of this drug and the control
      group, that were administered a 0.9% saline solution. Sedation was evaluated
      based on the Ramsay Scale and the administration of a 0.04 mg/kg dose of
      meperidine that was given to the patients who were agitated or anxious during the
      procedure. The invasive BP, HR and sedation score based on the Ramsay Scale were
      analyzed every 5 minutes and four different intervals were considered for the
      assessment: I1- start of the test; I2- 5 minutes after the start of the test; I3-
      median time of the test and I4- end of the test. RESULTS: The clonidine group
      presented better BP and HR stability and sedation efficacy while the control
      group presented a higher intake of meperidine (p<0.05). In the statistical
      analysis, the inference of the continuous variables was calculated using the
      Student's t-test or Mann-Whitney test and the chi2 or Fisher Exact Probability
      test was used for the categorical variables. CONCLUSION: This study demonstrated
      that clonidine was an efficient means to control BP and HR and provided a
      conscious sedation for patients submitted to a cineangiocardiography.

PMID- 17221037
TI  - Intima-media thickness in the origin of right subclavian artery as an early
      marker of cardiovascular risk.
AB  - OBJECTIVE: Common carotid artery intima-media thickness (IMT) is considered a
      factor of cardiovascular risk and an early marker of coronary artery disease.
      This study aimed to investigate the existence of a correlation between IMT in the
      carotid arteries and at the origin of the right subclavian artery, as well as to
      evaluate IMT in the subclavian artery as an earlier marker of cardiovascular
      risk. METHODS: One hundred and six consecutive patients, 52 males and 54 females,
      average age 51 years, underwent color Doppler ultrasonography to evaluate carotid
      and right subclavian arteries. The relationship between carotid IMT and right
      subclavian IMT was assessed using the Pearson's correlation coefficient analysis
      and a 95% confidence interval. Reliability of right subclavian artery IMT
      measurement for the diagnosis of early thickening (considering a > 0.8 mm carotid
      thickness as reference) was described as to sensitivity, specificity, positive
      predictive value, negative predictive value, and accuracy. Cut-off values for the
      right subclavian IMT were indicated by the ROC curve, and p values < or = 0.05
      were considered statistically significant. RESULTS: Out of the 41 patients whose
      carotid arteries were IMT-free, 30 (73%) had right subclavian artery IMT values >
      0.8 mm. The mean IMT value for the carotid artery was 0.87 mm (SD = 0.23) and for
      the subclavian artery, 1.17 mm (SD = 0.46), with a 0.31 correlation coefficient
      (95% CI: 0.12; 0.47). The ROC curve analysis indicated a cut-off value of 0.7 mm
      for the right subclavian artery IMT, using as reference a 0.8 mm cut-off value
      for the carotid artery (91% sensitivity, 27% specificity, 66% PPV, 65% NPV, and
      66% accuracy). CONCLUSION: Our study showed that carotid artery IMT correlates
      well with right subclavian artery IMT. With a 0.7 mm cut-off value, it is
      possible to detect IMT in the right subclavian artery earlier than in the carotid
      arteries. The IMT at the origin of the right subclavian artery can be considered
      an earlier marker for the assessment of cardiovascular risk.

PMID- 17221038
TI  - Evolutive echocardiographic study of the structural and functional heart
      alterations in obese individuals after bariatric surgery.
AB  - OBJECTIVE: To evaluate with Doppler echocardiography the reversibility of
      structural and hemodynamic changes in obeses after bariatric surgery. METHODS:
      Twenty-three patients (19 women = 82.6%) were studied. Mean age was 37.9 years.
      All subjects had Class III or Class II obesity with comorbidity and were
      submitted to bariatric surgery. Clinical and echocardiographic evaluation were
      performed preoperatively, in 6 months and 3 years after surgery. RESULTS:
      Preoperatively, the mean weight and blood pressure (BP) were respectively 128.7
      +/- 25.8 kg and 142.2 +/- 16.2 / 92.2 +/- 10.4 mmHg. Postoperatively, they showed
      important body weight reduction in 6 months (97.6 +/- 18.3 kg) and 3 years (83.6
      +/- 13.5 kg), and BP reduction in 6 months (128.5 +/- 16.1/80.7 +/- 9.9 mmHg)
      that remain stable in 3rd year. On echocardiogram, preoperatively, there was
      hypertrophy of the septum and posterior wall associated with normal diastolic
      dimension; the predominant LV geometric pattern was concentric remodeling (74%).
      At six months, thinning of the ventricular septum and LV posterior wall, and
      increase in LV diastolic dimension were demonstrated. At 3rd year, the
      predominant LV pattern was normal (69%), with reduction of LV mass and LV
      mass/height2 index. We noticed improved diastolic function, with an increased E/A
      ratio and a decreased LV isovolumic relaxation time. The Myocardial Performance
      Index was obtained retrospectively in 13 patients and improved in 6 months. There
      was an increase of the ejection time in 6 months and an elevation of the ejection
      fraction in 3rd year, suggesting improvement of the LV systolic function.
      CONCLUSION: The weight loss obtained with bariatric surgery promotes both
      structural and functional myocardial changes that improve cardiac performance.

PMID- 17221039
TI  - Cardiac morphofunctional injuries in patients with hepatitis C virus: doppler
      echocardiographic evaluation.
AB  - OBJECTIVE: To evaluate the possible morphological and functional heart injuries
      in hepatitis C virus patients. METHODS: Control-case study analyzing Doppler
      echocardiographic aspects in 31 hepatitis C virus patients and 20 controls.
      RESULTS: There were no significant difference in relation to the myocardial
      thickening, left ventricular diameters, circumferential shortening, ejection
      fraction, mitral valve flow velocities, tissue sistolic and diastolic mitral
      annular ones. CONCLUSION: Individuals with hepatitis C virus in the initial
      phases of the disease did not show morpho-functional abnormalities of the heart
      when evaluated by Doppler echocardiography.

PMID- 17221040
TI  - Increase in systolic blood pressure during exercise testing after heart
      transplantation: correlation with the clinical condition and ventricular function
      assessed by dobutamine stress echocardiography.
AB  - OBJECTIVE: Patients who underwent heart transplantation (HTX) experience a
      reduction in the elevation that is usual in systolic blood pressure during
      exercise testing. Of unknown origin, this phenomenon varies in frequency and
      intensity. The aim of this study was to analyze the relationship between systolic
      blood pressure increase (delta SBP) and clinical aspects, as well as variables
      measured during exercise testing (ET) and dobutamine stress echocardiography
      (DSE) in patients in the late post-transplantation course. METHODS: Forty-five
      men, mean age 49.04 +/- 10.19, underwent clinical assessment, ET and DSE 40.91 +/
      27.46 months after heart transplantation. Left ventricular wall motion score
      index and ejection fraction were assessed. Delta SBP < 35 mmHg during ET was
      considered abnormal (SBC,1995). RESULTS: No significant correlation was found
      between delta SBP and post-transplantation time, graft ischemic time, history of
      rejection, diltiazem dosage, oxygen uptake, ejection fraction, and wall motion
      score index (WMSI). Delta SBP was normal in 17 patients (Group I) and abnormal in
      28 (Group II). Patients of both groups did not differ significantly in regard to
      clinical features and ET and DSE results. CONCLUSION: Unlike other populations,
      no correlation was found between delta SBP during exercise testing and clinical
      condition or left ventricular function in heart transplant patients.
      Pathophysiological factors associated with delta SBP reduction during exercise
      testing remain unknown.

PMID- 17221041
TI  - Assessment of the general knowledge of emergency physicians from the hospitals of
      the city of Salvador (Brazil) on the care of cardiac arrest patients.
AB  - OBJECTIVE: To identify the proportion of emergency physicians certified in
      immersion courses (ACLS--Advanced Cardiac Life Support and ATLS--Advanced Trauma
      Life Support) correlating the variables of age, gender, medical specialty,
      academic title, and type of hospital with the level of theoretical knowledge on
      the care of Cardiac Arrest (CA) victims. METHODS: Emergency physicians from
      public and private hospitals of the city of Salvador, State of Bahia--Brazil,
      were consecutively evaluated from November, 2003 to July, 2004. They volunteered
      to participate in the study, and responded to a questionnaire consisting of
      information on the following variables of interest: professional profile,
      participation or not in ACLS and ATLS immersion courses, and cognitive assessment
      with 22 objective questions on Cardiopulmonary Resuscitation (CPR). A score of
      correct answers was calculated for each participant, and then designated as score
      variable. This questionnaire was validated based on the result of the score
      obtained by ACLS course instructors in Salvador, BA. RESULTS: Of the 305
      physicians who responded to the questionnaire, 83 (27.2%) had attended the ACLS
      course and had a mean score variable of 14.9+3.0 compared with the 215 physicians
      (70.5%) who had not attended the course and whose mean was 10.5+ 3.5 (p=0.0001).
      The mean score of the 65 cardiologists (21.5%) was 14.1+3.3 compared with the
      mean of 9.7+3.7(p=0.0001) of the 238 physicians (78.5%) from other specialties.
      No difference was observed in the mean scores between physicians who had attended
      the ATLS course or not (p=0.67). CONCLUSION: In the sample studied, theoretical
      knowledge on CPR was higher among physicians who had attended the ACLS course, as
      opposed to those who had attended the ATLS course. Cardiologists who had attended
      the ACLS demonstrated a higher theoretical knowledge on the care of CA patients
      when compared to physicians from other specialties taken as whole--Internal
      Medicine, Surgery, and Orthopedics.

PMID- 17221042
TI  - Trends in the risk of death from cardiovascular, cerebrovascular and ischemic
      diseases in thirteen States of Brazil from 1980 to 1998.
AB  - OBJECTIVE: Analyze the trends in the risk of death from circulatory diseases (CD)
      in thirteen states in Brazil between 1980 and 1998. METHODS: Data on mortality
      from CD, ischemic heart diseases (IHD), and cerebrovascular diseases (CVD) in
      thirteen states were obtained from the Ministry of Health data base. Populational
      estimates from 1980 to 1998 were calculated through interpolation, using the
      Lagrange method, based on data from the 1970, 1980, 1991 censuses, and 1996
      populational count. The trends were analyzed by multiple linear regression model.
      RESULTS: Mortality due to CD showed a trend towards decrease in most states. In
      Pernambuco state males presented increase in all age ranges, whereas in Goias
      increase was shown from 40 years of age on, and in Bahia and Mato Grosso, from 50
      years of age. Females showed increase starting at 30 in Mato Grosso, at 40 in
      Pernambuco, and in Goias, in the age ranging from 30 to 49 years of age. In
      Goias, increase was discreet in all other age ranges. As for IHD, mortality
      increase was reported in all age ranges in Mato Grosso and Pernambuco; in Bahia,
      Goias and Para, from 40 on. As for CVD, mortality increase was reported in all
      age ranges in Mato Grosso and Pernambuco; and from 40 on in Bahia and Goias.
      CONCLUSION: Significant increase in the risk of death from circulatory diseases
      could be observed in less developed states in Brazil.

PMID- 17221043
TI  - Hypertrophic cardiomyopathy: the importance of arrhythmic events in patients at
      risk for sudden cardiac death.
AB  - OBJECTIVE: To evaluate, in patients with hypertrophic cardiomyopathy and risk for
      SCD who underwent implantable cardioverter-defibrillator (ICD) implantation: a-
      the occurrence of arrhythmic events; b- the occurrence of clinical events and
      their correlation with arrhythmic events; c- the occurrence of ICD shock therapy
      and clinical and functional correlations; d- clinical and functional predictors
      of prognosis. METHODS: Twenty six patients with hypertrophic cardiomyopathy and
      risk factors for SCD undergoing ICD implantation from May, 2000 to January, 2004
      (mean follow-up = 20 months) were studied. Fourteen patients (53.8%) were females
      and the mean age was 42.7 years. ICD was indicated for primary prevention of
      sudden cardiac death in 16 patients (61.5%), and for secondary prevention in 10
      patients (38.5%). Twenty patients (76.9%) presented syncope prior to ICD
      implantation; half of them were related to ventricular fibrillation or sustained
      ventricular tachycardia, 15 (57.7%) had a history of familial sudden death, 12
      patients (46.2%) had nonsustained ventricular tachycardia on the 24-hour Holter
      monitoring, and five (19.2%) had an interventricular septal thickness greater
      than 30 mm. RESULTS: Four shock therapies were recorded by the ICD in potentially
      lethal arrhythmias (three patients with sustained ventricular tachycardia and one
      patient with ventricular fibrillation) during the follow-up. One death occurred,
      probably due to a thromboembolic stroke. Four patients had recurrence of syncope
      with no arrhythmic event recorded by the ICD. The statistical analysis showed a
      significant difference in early ICD shock therapy in patients whose
      interventricular septal thickness was greater than 30 mm. CONCLUSION: 1-
      occurrence of arrhythmic events in 50% of the patients; most of them (62%) were
      ventricular tachycardia, whether sustained (31%) or nonsustained (31%); in the
      remaining patients paroxysmal supraventricular tachycardia was observed. 2-
      recurrent syncope in the minority of the patients (16%), however not associated
      with the presence of arrhythmic events. 3- the presence of an interventricular
      septal thickness greater than 30 mm in the echocardiogram was associated with
      early shock therapy (p = 0.003). 4- absence of clinical or functional predictors.

PMID- 17221044
TI  - Case 4/2006: thirteen-year-old teenager with single left ventricle, ventriculo
      arterial discordance with left aorta, pulmonary stenosis and previous pulmonary
      systemic shunt.

PMID- 17221045
TI  - Postprandial hyperglycemia: treating its atherogenic potential.

PMID- 17221046
TI  - High-density lipoproteins: metabolic, clinical, epidemiological and therapeutic
      intervention aspects. An update for clinicians.

PMID- 17221047
TI  - Inserting otorhinolaryngology in the medical course.

PMID- 17221048
TI  - Hearing impairment diagnosis in Pernambuco: services of intermediate complexity-
      2003.
AB  - Universal and equal access to health care, granted to the population as of the
      brazilian constitution of 1988, made it easier the early diagnosis of hearing
      impairment. Thus, through the sistema unico de saude (sus), public and private
      health care providers granted this health coverage to the whole brazilian
      population, in the different levels of complexity. AIM: this paper aims at
      studying the supply of intermediate complexity hearing impairment diagnosis in
      pernambuco in the first semester of 2003. MATERIALS AND METHODS: a study of
      series analyzed 17669 procedures and 372 professionals in the field of hearing
      impairment in the 185 municipalities in the state of Pernambuco--Brazil--data
      taken from the outpatient information system of the ministry of health. RESULTS:
      the results showed that the procedures are being carried out in only five
      municipalities, most of them managed in municipal units. We also identified an
      unequal distribution of diagnostic procedures. CONCLUSION: we then concluded that
      much is still necessary to provide hearing impairment diagnostic in a horizontal
      fashion, considering the community differences through an universal, integrated
      and efficient model, as the one proposed by the sistema unico de saude.

PMID- 17221049
TI  - Prevalence of Streptococcus pyogenes as an oropharynx colonizer in children
      attending daycare: a comparative study of different regions in Brazil.
AB  - Thirty percent of acute pharyngotonsillitis is caused by Streptococcus pyogenes,
      which increased the risk of glomerulonephritis and rheumatic fever. Children
      attending daycare centers have a higher incidence of these infections. AIM: to
      identify and compare the prevalence of Streptococcus pyogenes in the oropharynx
      of children who are enrolled and who are not enrolled in daycare centers in
      different regions of Brazil. MATERIALS AND METHODS: A prospective study of two
      hundred children from Sao Paulo/SP and Porto Velho/RO. Children from each city
      were divided into two groups: those attending, and those not attending daycare
      centers. Swabs of the oropharynx were taken for bacteriological culture and
      identification. RESULTS: The prevalence of Streptococcus pyogenes in the Sao
      Paulo groups were 8% and 2% for daycare and control groups, which was
      statistically significant (p=0.02). The prevalence in children from Porto
      Velho/RO was 24% and 16% for daycare and control groups, which was statistically
      significant (p=0.015). Statistical analysis also showed a significant difference
      between the corresponding groups in the two locations (p<0.01). CONCLUSION: These
      results show that daycare attendance is a risk factor for oropharyngeal
      streptococcal colonization; this was seen in different populations, but was
      statistically significance in only one of the two samples.

PMID- 17221050
TI  - Subperiosteal facelift: a 5-year experience.
AB  - In classic rhytidectomy, there is little improvement in the center portion of the
      face. Aesthetic correction of malar prominence ptosis, accentuated nasolabial
      line, and jawl line, in most of the cases, require different approaches, such as
      the subperiosteal facelift. AIM: to show the cases and to evaluate the results
      and complications of subperiosteal facelift in the our service. PATIENTS AND
      METHODS: From January of 2001 to December of 2005, 25 patients, ranging from 44
      to 60 years, 24 females, were submitted to subperiosteal facelift. Results and
      complications were retrospectively appraised. RESULTS: Of these, 20 presented
      satisfactory results, 4 presented aesthetic deficits noticed both by the patients
      and by the surgeon, and 1 presented aesthetic deficit needing revision surgery.
      All the patients presented improvement of nasolabial line, malar prominence and
      better definition of the jawl line. Revision surgery was necessary in one patient
      that referred little improvement. Four patients presented skin retraction in
      malar area due to the suspension sutures. A patient presented transitory
      paralysis of the front branch of the facial nerve. CONCLUSION: Subperiosteal
      facelift with temporal access has shown satisfactory results in the great
      majority of the cases.

PMID- 17221051
TI  - Topical mitomycin C effect on swine vocal folds healing.
AB  - Several adjuvant therapies to surgery have been used to modulate the healing
      process of vocal folds, including topic mitomycin (MTC). AIM: to evaluate the
      effect of topical MTC in the healing process of vocal folds 30 days after the
      exeresis of a mucosal fragment with CO2 laser in a swine model (control group
      without mitomycin and study group with topical MTC), with collagen deposition
      measurement. STUDY TYPE: prospective experimental in swine. METHODS: two groups
      of 6 swine each were subjected to exeresis of a mucosal fragment of the vocal
      fold with CO2 laser. Immediately after the procedure MTC was applied topically
      for three minutes on the study group. Thirty days later the animals were
      slaughtered and samples of the vocal folds were collected for histological
      analysis, with the purpose of quantifying collagen deposition by Picrosirius Red
      stain. RESULTS: the average area of total collagen in the vocal folds in the
      control group was 2.648,03 microm2, whereas in the study group it was 2.200,30
      microm2 (p=0.0043). CONCLUSION: topical application of MTC after the exeresis of
      a mucous fragment of vocal fold with CO2 laser in swine significantly decreased
      total collagen deposition.

PMID- 17221052
TI  - Clinical and ultrastructural study after partial inferior turbinectomy.
AB  - We report clinical and histological results obtained after partial inferior
      turbinectomy (PIT), surgery indicated for the treatment of chronic nasal
      obstruction. METHODS: Twenty patients were divided into two groups submitted to
      PIT plus septoplasty and PIT alone. The patients were reassessed clinically and
      histologically by means of a biopsy of the regenerated areas in the inferior
      turbinates at two different times after PIT, i.e., after 8 to 12 months (group A)
      and after two years (group B). RESULTS: The clinical results proved to be
      satisfactory for the relief of nasal obstruction in group A and unsatisfactory in
      group B. However, better histological results with better recovery and epithelial
      differentiation of the regenerated mucosa of the inferior turbinates after PIT
      were observed in group B. CONCLUSION: Surgery proved to be effective on a short
      term but not on a long-term basis, and histological recovery did not accompany
      improvement of clinical signs and symptoms.

PMID- 17221053
TI  - Hearing: a pediatricians approach.
AB  - Hearing plays a fundamental role in a child's global development; however, some
      professionals do not realize how much they may contribute to mitigate the
      sequelae caused by hearing impairment. AIM: to collect data on pediatricians
      approaches in a city in the country side of Santa Catarina State, regarding the
      early detection of hearing impairment and identify the methodology utilized for
      its diagnosis. STUDY DESIGN: Historical Cohort with Cross-Sectional Cohort.
      MATERIALS AND METHODS: Analysis of questionnaires with nine multiple choice
      questions and ten open questions. RESULTS: 62% reported that their training in
      hearing disorders happened during their medical course; high risk patients are
      referred to the otorhinolaryngologist (92%); 83% said they are aware of the
      evaluation techniques; 55% stated they were not aware of the different types of
      hearing loss; only 25% reported they knew about the levels of hearing loss and
      42% of the interviewees believe a child may have fruitful use of a hearing aid
      before six months of age. CONCLUSION: There is the need of more information about
      the importance of early diagnosis, as well as the methods used for this end.

PMID- 17221054
TI  - Endoscopic frontoplasty: 3-year experience.
AB  - Endoscopic forehead lift (EFL) represents a significant progress, even replacing
      the classic coronal and pretriquial techniques. AIM: To demonstrate a series of
      cases and to evaluate results and complications with EFL in the Department of
      Otorhinolaryngology of the Federal University of Uberlandia. MATERIALS AND
      METHODS: From January 2001 to January 2004, 67 patients were submitted to EFL,
      and 7 of these were submitted to the so called "triangles technique". Their ages
      ranged between 38 and 59 years; and 65 (97%) were females. RESULTS: Of these, 56
      patients presented satisfactory result and 2 presented aesthetic deficits noticed
      by the surgeon and the patient. Of the 7 patients submitted to the "triangles
      technique", all showed satisfactory results. All the patients had improvements on
      their ptosis of the lateral and glabellar third of the brows and reduction in
      vertical and frontal wrinkles. Revision surgery was necessary in 2 patients that
      had ptosis recurrence. There was one unilateral paralysis of the front branch of
      the facial nerve. With the "triangles technique", 5 patients presented visible
      scars. CONCLUSION: EFL is a technique that produces satisfactory results in the
      great majority of patients, with low complication rates.

PMID- 17221055
TI  - Temporomandibular joint arthrocententesis: evaluation of results and review of
      the literature.
AB  - AIM: This study was designed to investigate the effects of arthrocentesis on the
      improvement of internal derangement symptoms and jaw function in a series of
      patients with anterior disc displacement and closed lockjaw. PATIENTS AND
      METHODS: The study was based on a review of patients records before and after
      treatment using clinical examinations and radiographs. Visual analog scales were
      used to measure pain before and after arthrocentesis. Six patients (12
      temporomandibular joints) with closed lock symptoms (2 cases) and internal
      derangements (4 cases) were treated at the Oswaldo Cruz Hospital. The mean follow
      up was 11.5 months. RESULTS: The mean maximum vertical opening before treatment
      was 31.83 mm and after arthrocentesis was 36.50 mm. The visual analog scale for
      pain before treatment was 7 points (mean) and after arthrocentesis the mean was
      4.3. CONCLUSION: Arthrocentesis was shown to be effective in reducing pain and
      increasing jaw motion in this series of cases.

PMID- 17221056
TI  - Histologic description of acquired cholesteatomas: comparison between children
      and adults.
AB  - Cholesteatoma is constituted of matrix, perimatrix and cystic content. Some
      authors affirm that, in children, its clinical behavior is more aggressive of the
      than in adults. AIMS: Histologic compared cholesteatomas of children and adults.
      METHODOLOGY: 74 cholesteatomas been analyzed, being 35 of pediatrics patients
      (<18 years). The average number of cellular layers and hyperplasia in the matrix
      had been evaluated; thickness, delimitante epithelium, fibrosis, inflammation and
      granuloma in the perimatrix. The analysis statistics was carried through with
      program SPSS 10.0, using the coefficients of Pearson and Spearman, test of chi
      square and t test. The number of cellular layers in the matrix was of 8.2+/-4.2.
      The hyperplasia appears in 17%, fibrosis in 65%, granuloma in 12% and the
      delimitante epithelium in 21%. The perimatrix presented a medium one of 80
      micrometers (37 the 232), minimum value zero and maximum value 1.926. The
      histological degree of inflammation was considered of moderate the accented one
      in 60%. When applying the coefficient of Spearman enters the inflammation degree
      and average of cellular layers of the matrix with the variables of the measure of
      thickness of the perimatrix we find correlations, significant, with moderate
      magnitudes of the great ones (rs=0.5 and P<0.0001). CONCLUSION: Adults
      colesteatomas of and child had not been identified to morphologic differences
      between. We find correlation enters the intensity of the inflammation and of the
      average of cellular layers of the matrix with the thickness of the perimatrix,
      what it can predict its aggressiveness, more studies are necessary to define the
      paper of this finding in pathogenesis of cholesteatoma.

PMID- 17221057
TI  - Endoscopic findings in children with stridor.
AB  - Congenital and acquired airway diseases are responsible for upper respiratory
      distress and stridor in children. In neonatal intensive care units, we have seen
      increased survival in premature babies, but also a high incidence of airway
      complications related to intubation, which present as stridor. AIM: To review
      endoscopic findings in children with stridor. STUDY DESIGN: a cross-sectional
      cohort study. METHODS: A retrospective analysis was done of 55 cases of children
      with stridor who underwent endoscopic exams, between January 1997 and December
      2003. RESULTS: 69% were aged below one year. The main indications for endoscopy
      were post-extubation stridor (63.63%) and evaluation of neonatal stridor
      (21.82%). Many associated diseases were seen, including lung diseases (60%),
      neurological condition (45.4%), and GERD (40%). The main endoscopic findings and
      indications for tracheotomy were subglottic stenosis (27.27%) and airway
      inflammatory process (21.82%) occurring in children under five years old.
      Congenital disorders were more frequent in children under age one year.
      CONCLUSION: Neonatal stridor has many causes; those related to tracheal
      intubation are more frequent in hospitals that treat more complex diseases.
      Pediatricians and otorhinolaryngologists should know the main causes of stridor
      and perform detailed clinical evaluations to determine case severity. The
      endoscopic examination, must be meticulous.

PMID- 17221058
TI  - GSTT1 and GSTM1 polymorphism in cigarette smokers with head and neck squamous
      cell carcinoma.
AB  - Gene variability related to carcinogen activation and detoxification may
      interfere with susceptibility to head and neck cancer. AIM: To investigate the
      relation between GSTT1 and GSTM1 null polymorphisms and the risk of head and neck
      squamous cell carcinoma in cigarette smokers. MATERIAL AND METHOD: A case-control
      study conducted at the Sao Jose do Rio Preto Medical School, Brazil. GSTM1 and
      GSTT1 null genotype frequencies were evaluated by multiplex PCR in 45 cigarette
      smokers with head and neck squamous cell carcinomas and 45 cigarette smokers
      without this disease. RESULTS: The oral cavity was the most prevalent tumor site
      for squamous cell carcinoma. The GSTT1 null genotype was found in 33.3% of the
      Experimental Group and 23.3% of the Control Group (p= 0.311). Experimental and
      Control Groups had GSTM1 null genotype frequencies of 35% and 48.3% (p=0.582). No
      association between alcohol consumption and GSTT1 and GSTMI null genotypes was
      found in these groups (p-values>0.05). There were more men, and alcohol
      consumption was prevalent in both groups. CONCLUSION: In this study we were
      unable to show a correlation between GSTM1 and GSTT1 genotypes and the
      development of head and neck squamous cell carcinomas in cigarette smokers.

PMID- 17221059
TI  - Standardization of acoustic measures for normal voice patterns.
AB  - Studies have established that normative data is necessary for acoustic analysis.
      The aim of the present study is to standardize fundamental frequency measures
      (fo), jitter, shimmer and harmonic-noise ratio (HNR) for young adults with normal
      voice. METHOD: 20 males and 20 females, between 20 and 45 years, without signs
      and symptoms of vocal problems; CSL-4300 Kay-Elemetrics; vowels /a/ and /e/.
      RESULTS: for females, vowels /a/ and /e/ had average measures of: fo 205.82 Hz
      and 206.56 Hz; jitter of 0.62% and 0.59%; shimmer of 0.22 dB and 0.19 dB; PHR of
      10.9 dB and 11.04 dB, respectively. For males, vowel /a/ and /e/ had average
      measures of: fo 119.84 Hz and 118.92 Hz; jitter of 0.49% and 0.5%; shimmer of
      0.22 dB and 0.21 dB; HNR 9.56 dB and 9.63 dB, respectively. Both fo and NHR
      female measures were significantly higher than their male counterparts.
      CONCLUSION: our results differ from the literature; therefore, it is important to
      standardize the program in use.

PMID- 17221060
TI  - High-frequency audiometry in young and older adults when conventional audiometry
      is normal.
AB  - High-frequency audiometry can detect early changes in auditory sensitivity
      resulting from processes such as aging. Nonetheless its use is still limited, and
      additional studies are required to establish its use, particularly among older
      adults. AIM: To compare pure tone thresholds for frequencies from 250 Hz to 16
      kHz in young and older adults, with or without audiologic complaints. METHOD:
      Pure tone sensitivity to 250 Hz to 16 kHz was assessed with an AC-40 audiometer
      in 64 adults, evenly distributed in young (25 to 35 years-old) and older (45 to
      55 years-old) adults of both sexes. This is a cross-sectional study. RESULTS:
      Although all participants presented normal audiometry in frequencies from 250 Hz
      to 8 kHz, according to clinical parameters, older adults had significantly higher
      thresholds compared to young adults, according to statistical parameters, with
      greater significance in higher frequencies (8 to 16 kHz). Presence or absence of
      clinical complaints did not distinguish thresholds. CONCLUSIONS: The process of
      auditory aging, including loss of sensitivity to higher frequencies, can be
      detected at earlier ages than those usually investigated. High frequency
      audiometry is an important instrument to distinguish auditory sensitivity in
      young and older adults, even for those considered as audiologically normal.

PMID- 17221061
TI  - Identifying dead regions in the cochlea through the TEN test.
AB  - An audiogram is not sufficient to indicate cochlear dead regions. AIM: To
      investigate cochlear dead regions in sensorineural hearing loss subjects using
      the TEN test. SITE: CEDALVI/ HRAC-USP-Bauru/Sao Paulo/Brazil, August 2003 to
      February 2004. STUDY DESIGN: A contemporary cross-sectional cohort study.
      MATERIAL AND METHODS: The TEN test was applied in three groups: G1(5 women with
      pure-tone thresholds within normal limits); G2(4 women and 5 men with moderate
      sensorineural flat hearing loss); G3(19 women and 24 men with mild to severe
      sloping sensorineural hearing loss). RESULTS: In the G1 group the TEN value
      required to eliminate the test tone was, on average, close to the absolute
      threshold for all frequencies. No dead regions were found in the ears tested in
      group G2. 76 ears were tested in group G3, and six showed no evidence of dead
      regions in the cochlea. CONCLUSIONS: The TEN test was an effective test to
      indicate a dead region in the cochlea of subjects with sloping sensorineural
      hearing loss. There is evidence that pure-tone detection is different for
      subjects with high frequency sensorineural hearing loss and flat hearing loss; we
      observed a significant difference between the masked threshold and the absolute
      threshold only in sloping hearing loss and not for flat hearing loss.

PMID- 17221062
TI  - Functional balance associated factors in the elderly with chronic vestibular
      disorder.
AB  - Daily activities can be challenging for the elderly. AIM: To study the
      association between functional balance, evaluated by the Berg Balance Scale
      (BBS), sociodemographics, clinical and mobilility (Timed up and go test-TUGT,
      Dynamic Gait Index-DGI) variables in the elderly with chronic vestibular
      disorder. MATERIALS AND METHODS: A series study with one hundred and twenty
      elderly with chronic vestibular disorder. We performed the Mann-Whitney test, the
      Kruskal-Wallis test followed by Dunn test and the Spearman Coefficient ([FORMULA:
      SEE TEXT]). RESULTS: Statistically significant associations and correlations were
      observed between total BBS score and age ([FORMULA: SEE TEXT]=-0.354; p<0.001),
      age group (p<0.001), number off illnesses (p=0.030), number of illnesses
      ([FORMULA: SEE TEXT]=-0.287; p=0.001), number of medications (p=0.014), number of
      medications ([FORMULA: SEE TEXT]=-0.274; p=0.002), recurrent falls (p=0.010),
      tendency to fall (p=0.002), topographic diagnosis of central vestibular disorder
      (p<0.001) and periodicity of dizziness (p=0.039), TUGT ([FORMULA: SEE TEXT]=
      0.709; p<0.001) and DGI ([FORMULA: SEE TEXT]=-0.748; p<0.001). CONCLUSIONS:
      Functional balance in the elderly with chronic vestibular disorders evaluated by
      the BBS is worse when associated with aging, with a more advanced age group (80
      years or more), increasing number of illnesses, presence of five or more
      illnesses, use of multiple medications, recurrent falls, tendency to fall,
      central vestibular syndromes, daily dizziness, mobility and gait impairments.

PMID- 17221063
TI  - Phone positioning influence in high-frequency audiometry.
AB  - Research considers high frequency tonal audiometry as a tool for the early
      diagnosis of auditory alterations derived from etiological agents. AIM: to
      investigate possible differences in high frequency audiometry of individuals with
      normal hearing, based on the person who places the earphone. PATIENTS AND METHOD:
      clinical and experimental study with 55 undergraduate students from a country
      side branch of the Sao Paulo State University, with normal hearing, underwent two
      tests each; for the first, the evaluator positioned the earphone on the
      participant; for the second one, the participant did it by him/herself. An AC40
      audiometer calibrated to emit pure tone was used in the frequencies of 10, 12.5,
      and 16 kHz. RESULTS: The kappa(k) coefficient statistical analysis was used to
      verify the agreement between the two ways of earphone positioning of earphone,
      bearing a [FORMULA: SEE TEXT]0.70 kappa value as a criterion. Results attained
      for both ears were below this criterion, with k average of 0.50. DISCUSSION:
      results indicate a risk of compromising the exam reliability when the patient
      him/herself adjusts phone to his/her own ear. CONCLUSION: when performing
      audiometric assessment, this variable must be considered in order to attain
      reliable results.

PMID- 17221064
TI  - Treatment of obstructive sleep apnea and hipoapnea syndrome with oral appliances.
AB  - Obstructive sleep apnea and hipoapnea syndrome (OSAHS) is a disorder that affects
      about 4% of the adult population, and besides the social problems associated to
      snoring and extreme day time sleepiness, it is preoccupying since it may cause
      pulmonary hypertension and cardiac failure. REVIEW AND DISCUSSION: Through a
      literature review, we discuss the use of oral appliances to treat this condition,
      in regards of therapy effectiveness and limitations, main clinical symptoms,
      major occlusal side effects, rate of improvement and patient satisfaction.
      CONCLUSIONS: We concluded that the use of oral appliances should be a first
      choice treatment for mild to moderate OSAHS, being dental, joint and muscular
      discomforts, hypersalivation and xerostomia, the most frequent clinical symptoms,
      with light occlusal side effects that normally do not bother the patients, with a
      good degree of improvement and high satisfaction index.

PMID- 17221065
TI  - Oral complications of radiotherapy in the head and neck.
AB  - Radiotherapy is a treatment modality largely used for head and neck malignancies.
      However, high doses of radiation in large areas, including the oral cavity,
      maxilla, mandible and salivary glands may result in several undesired reactions.
      Mucositis, candidosis, disgeusia, radiation caries, osteoradionecrosis, soft
      tissue necrosis and xerostomia are some of radiotherapys complications. AIM: The
      aim of this study is to briefly review the side effects that may be seen in the
      oral cavity during or after radiotherapy treatment in the head and neck region.
      BASIC METHOD USED: Review of relevant literature. STUDY DESIGN: Literature
      review. RESULTS: Radiotherapy is still associated with several side effects,
      significantly affecting patients quality of life. CONCLUSIONS: A
      multidisciplinary treatment, including physicians, dentists, speech therapists,
      nutritionists, and psychologists, is the best alternative to minimize, or even
      prevent such reactions.

PMID- 17221066
TI  - "Hybrid" lesion of desmoplastic and conventional ameloblastoma:
      immunohistochemical aspects.
AB  - Ameloblastoma is a benign epithelial odontogenic tumor and is the most commonly
      encountered odontogenic tumor in the jaws. Histologically, ameloblastomas occur
      in different patterns, including plexiform pattern and follicular pattern.
      "Hybrid" lesion of ameloblastoma is a tumor variant in which histologically,
      areas of follicular or plexiform ameloblastoma coexist with characteristic areas
      of ameloblastoma exhibiting pronounced stromal desmoplasia (desmoplastic
      ameloblastoma). The purpose of this article is to present a case of "hybrid"
      lesion of desmoplastic ameloblastoma (AD) and conventional, and investigate
      extracellular matrix proteins such as tenascin, fibronectin, and type I collagen.

PMID- 17221067
TI  - Nasal schwannoma.

PMID- 17221068
TI  - Painful tongue leiomyoma.

PMID- 17221069
TI  - Primary malignant orbit melanoma.

PMID- 17221070
TI  - Auricular perichondritis by piercing complicated with pseudomonas infection.

PMID- 17221071
TI  - Nasal resistance and OSA.

PMID- 17221074
TI  - Evaluation of graduate studies in public health in Brazil.

PMID- 17221075
TI  - [Evolution of the international intellectual property rights system: patent
      protection for the pharmaceutical industry and access to medicines].
AB  - This article discusses the evolution of the international intellectual property
      rights system in three phases and the implications for public health, especially
      for the implementation of policies for access to medicines. During the first
      phase, characterized by the Paris and Berne Convention, signatory countries
      defined which technological fields should be protected (or not). Under the second
      phase, with the enforcement of the WTO TRIPS Agreement, countries are obliged to
      grant patent protection for all technological fields, including for the
      pharmaceutical industry. Within their national legislations, countries also have
      the opportunity to implement access to TRIPS flexibilities for medicines. With
      the third phase, characterized by the negotiation and signing of bilateral and
      regional free trade agreements, countries will have to implement TRIPS-plus
      provisions which may have negative implications for the TRIPS flexibilities as
      well as for policies for access to medicines. The authors conclude that the
      currently proposed international intellectual property rights system favors
      patent-holder rights and that a balance is needed between patent holders' and
      health rights.

PMID- 17221076
TI  - [Effect of food fortification with iron on childhood anemia: a review study].
AB  - A systematic review was conducted to identify studies assessing the effect of
      food fortification with iron on childhood anemia. The MEDLINE, LILACS, and PubMed
      databases and WHO and PAHO sites were searched with no time limitation, including
      articles published in Portuguese, English, or Spanish, using the following key
      words and their combination: food fortification, iron, effectiveness, efficacy,
      anemia, flour, staple foods, interventions, and children. Of 21 studies reviewed,
      only one failed to report a positive, favorable effect of iron fortification,
      indicating the possibility of publication bias. The studies showed important
      methodological limitations. The two studies with the best methodological scores
      showed opposite results, highlighting the need for larger trials with better
      planning to explore this hypothesis.

PMID- 17221077
TI  - Ecosystem approaches and health in Latin America.
AB  - Important environmental changes that have become increasingly pronounced in the
      last two centuries and that are seriously affecting human health require the
      development of integrated and participatory scientific approaches that can result
      in proposals for institutional and public policy changes. The purpose of this
      article is to offer some elements that can contribute to a line of reflection
      based on studies with ecosystem approaches in the Latin America context. The
      authors begin with a brief description of current scientific literature in public
      health that links ecosystems and human health in Latin America; next, they
      describe and compare the two prevailing trends that form the basis for the
      theoretical and methodological debates on ecosystem approaches; they also review
      the empirical research in Latin America or concerning Latin American countries in
      which an ecosystem approach has been adopted. The results point to limited
      scientific output on the interface between ecosystems and human health; aspects
      involving public participation and implementation of institutional changes and
      public policies are still in a rather incipient stage.

PMID- 17221078
TI  - Which body mass index is best associated with risk of diabetes mellitus and
      hypertension in a Japanese-Brazilian population?
AB  - The objective of this study was to evaluate the impact of different body mass
      index (BMI) ranges associated with the risk of diabetes and hypertension in
      Japanese-Brazilians. This cross-sectional study was based on data from 1,330
      Japanese-Brazilians > 30 years of age who participated in a population-based
      survey on the prevalence of diabetes mellitus and associated diseases. Glucose
      tolerance status was classified according to WHO criteria and blood pressure
      levels according to the VI-JNC. Odds ratios for diabetes and hypertension were
      calculated for different BMI ranges; for different BMIs, sensitivity and
      specificity for percentiles 25, 50, 75, 90 and 95 were obtained. Increased odds
      ratios for diabetes mellitus and hypertension were observed with BMI values > 25
      kg/m(2). The 50th percentile corresponded to the highest sensitivity and
      specificity for the identification of risk for both diseases. Our results suggest
      that BMI values proposed by WHO should also be useful for this group of Japanese
      descendants in the assessment of risk for DM and hypertension.

PMID- 17221079
TI  - Health inequalities based on ethnicity in individuals aged 15 to 64, Brazil,
      1998.
AB  - This study aimed to analyze inequalities in health status and utilization of
      medical consultations and hospital services by Brazilian young and adult
      populations according to ethnicity. The survey analyzes a representative sample
      of the Brazilian population aged 15 to 64 years, except those living in the rural
      area of the Amazon. The prevalence of fair or poor health status was
      substantially higher among black men, white women, and black women. The influence
      of gender and ethnicity remains significant after adjusting for age and
      socioeconomic conditions (OR = 1.11; 1.49 and 1.86 respectively). Differences
      between blacks and whites decrease with age, but increase with socioeconomic
      status. There were 10% more medical consultations among white individuals. The
      differences were more striking among young people who reported good health
      status. For individuals with fair or poor health, no differences were observed in
      frequency of medical consultations between blacks and whites. There were no
      significant differences in hospitalization rates. With regard to health status,
      differences between blacks and whites were striking. However, the same was not
      true for utilization of health services.

PMID- 17221080
TI  - Mini-Mental State Examination norms in a community-dwelling sample of elderly
      with low schooling in Brazil.
AB  - The objective of this study was to assess Mini-Mental State Examination norms of
      a functionally normal sample of community-dwelling elderly. Illiterate and low
      educated subjects who scored less than 5 on the Pfeffer Functional Activities
      Questionnaire (PFAQ) [n = 397; female = 269; mean age = 72.15 (SD = 7.24) years]
      had the 5th, 25th, 50th, and 75th percentiles calculated according to age (65-74;
      75-84 years). Overall MMSE score was 21.97 (SD = 4.48). Mean MMSE for illiterate
      younger individuals was 19.46 (SD = 3.47), and the quartile distribution was 14,
      17, 19, and 21. MMSE of subjects with 1-8 years of schooling was 23.90 (3.87),
      and the distribution was 15, 22, 24, and 27. MMSE of older illiterate subjects
      was 18.11 (SD = 3.63), and the distribution of scores was 13, 16, 18, and 20,
      whereas subjects with 1-8 years of schooling scored 23.81 (SD = 4.01) and the
      distribution was 15, 22, 24, and 27. These MMSE normative data may help improve
      the detection of cognitive impairment in Brazil, mainly in the primary clinical
      setting.

PMID- 17221081
TI  - [The epidemiological approach to health inequalities at the local level].
AB  - What are the advantages and limitations of epidemiology for decreasing health
      inequalities at the local level? To answer this question, the current article
      discusses the role of epidemiology. The hypothesis is that epidemiology produces
      useful knowledge for local management of interventions aimed at reducing health
      inequalities, expressed in spaces built by human communities through social and
      historical processes. Local production of epidemiological knowledge should
      support action by social actors in specific situations and contexts, thus
      renewing the appreciation for ecological designs and georeference studies. Such
      knowledge output and application are also an organizational phenomenon.
      Organizations can be seen as "conversational networks". In conclusion, strategic
      and communicative actions by health workers should provide the central thrust for
      defining new health care and management models committed to decreasing health
      inequalities, with epidemiology playing a key role.

PMID- 17221082
TI  - [Receptiveness and changes in the nursing work process in healthcare units in
      Campinas, Sao Paulo, Brazil].
AB  - This article describes changes in the nursing work process resulting from
      implementation of the process referred to as "receptiveness", following
      introduction of the Paideia Family Health Program in health care units in
      Campinas, Sao Paulo, Brazil, since 2001. Data were collected through participant
      observation and semi-structured interviews to examine the nursing work process,
      specifically in relation to "receptiveness". The analysis was based on two
      possible definitions of "receptiveness": as an attitude towards users and their
      needs, and as a device for reorganizing the work process. The study also analyzes
      "receptiveness" in relation to: organization of the work process, guarantee of
      accessibility, expanded demands on the health service and health team, changes in
      the nursing work process, humanization, and bonding.

PMID- 17221083
TI  - Gender differences in self-reported morbidity: evidence from a population-based
      study in southern Brazil.
AB  - This paper aims to assess variations in self-reported morbidity between men and
      women using six different measures of reported illness. The cross-sectional study
      was conducted in the municipality of Rio Grande, southern Brazil. Demographic,
      socioeconomic, and morbidity data were collected from a probabilistic sample of
      1,260 persons aged 15 years or over, using a specific questionnaire. Statistical
      analysis included a multivariate Poisson regression analysis. Prevalence Ratios
      (PR) with 95% confidence intervals (95%CI) were calculated. After adjusting for
      some confounding variables (age, race, unemployment, marital status, income,
      social class, and education), women showed greater risk of any symptom (PR =
      3.21; 95%CI: 2.71-3.83), three or more symptoms (PR = 4.22; 95%CI: 2.97-5.98),
      potentially serious symptoms (PR = 1.75; 95%CI: 1.31-2.34), poor/fair health (PR
      = 1.78; 95%CI: 1.37-2.32), and minor psychiatric disorders (PR = 1.76; 95%CI:
      1.31-2.37). The study revealed dissimilarity in self-reported morbidity between
      men and women in southern Brazil, but with different degrees depending on type of
      morbidity. This excess can be explained by gender difference in health-seeking
      behavior for perceiving or reporting health problems.

PMID- 17221084
TI  - Early determinants of smoking in adolescence: a prospective birth cohort study.
AB  - In a prospective birth cohort study in Brazil, the prevalence and early risk
      factors for smoking in adolescence were investigated. All 1982 hospital-born
      children in Pelotas, Rio Grande do Sul, Brazil, were enrolled in a birth cohort
      study (N = 5,914; boys: 3,037; girls: 2,877). All male participants were searched
      in 2000 when enrolling in the national army, and 78.8% were traced. In 2001, a
      systematic sample of 473 girls was interviewed, representing a follow-up rate of
      69.1%. Among males, 48.6% (95%CI: 46.6-50.7) had ever tried smoking and 15.8%
      (95%CI: 14.3-17.3) were daily smokers. Among females, 53.1% (95%CI: 48.6-57.6)
      had ever tried smoking and 15.4% (95%CI: 12.1-18.7) were daily smokers. Boys born
      to single mothers and those with fathers with low schooling were more likely to
      smoke in adolescence. Girls from low-income families, with mothers who smoked
      during pregnancy, and fathers with alcohol-related problems were more likely to
      smoke. Although the smoking prevalence was similar in boys and girls, risk
      factors for smoking were different between the sexes. Social environment appears
      to be the strongest predictor of tobacco use in adolescence.

PMID- 17221085
TI  - [The implementation of decentralized health systems: a comparative study of five
      cases in Bahia, Brazil].
AB  - Understanding the effects of health decentralization policies in Brazil requires
      different methodological approaches to capture the issue's complexity from
      distinct angles. Five case studies were thus performed to evaluate the degree of
      implementation of components related to decentralization of the health system
      management in selected municipalities (counties) in Bahia State, Brazil. A
      logical model was elaborated with definitions related to policy goals. A
      comparative study of the five municipalities, considered "exemplary cases",
      showed that decentralization alone does not explain the organizational changes in
      the municipal health systems. Local government characteristics such as the
      municipal master plan, governing capacity, and governance proved important for
      heath care changes. The main problems and insufficiencies were found in the
      system's management and quality of healthcare delivered to the population. The
      authors discuss their findings and identify critical areas for future
      interventions with special emphasis on the institutionalization of planning and
      evaluation and the development of inter-sector projects.

PMID- 17221086
TI  - ["Birth weakness": cultural meanings of maternal impressions for infant health in
      Northeast Brazil].
AB  - Pregnancy encompasses socio-cultural, historical, and affective dimensions that
      process various meanings in women's bodies. Each society constructs popular
      concepts, practices, and explanatory models that differ from the biomedical model
      and aim to protect the mother and fetus and foster a healthy pregnancy. This
      qualitative study, based on interpretative anthropology, unveils the experiences
      of 27 poor women and their repercussions on the malnutrition of their infants,
      treated at a Childhood Malnutrition Treatment Center in Fortaleza, Northeast
      Brazil. From January to June 2004, ethnographic and narrative interviews were
      conducted on so-called "birth weakness", in addition to participant observation
      of outpatient, nursing, and home childcare. The mothers believed that their own
      physical and emotional suffering and precarious nutritional status were
      "imprinted" on the fetus, resulting in the child's malnutrition. While the ethno
      etiology of "weakness" points to factors outside the body that involuntarily
      affect the pregnant mother, the medical view tended to incriminate the mother
      herself. It is necessary to understand the mothers' narratives, sympathize with
      their suffering, and spawn a closer approach between the popular and biomedical
      concepts.

PMID- 17221087
TI  - [Prevalence of fracture risk estimated by quantitative ultrasound of the
      calcaneus in a population of postmenopausal women].
AB  - A strong aging tendency is currently being observed in the world population,
      leading to an increase n the prevalence of such diseases as osteoporosis and
      fractures. This study aimed to determine the prevalence of fracture risk,
      estimated by quantitative ultrasound of the calcaneus in a population of
      postmenopausal women residing in the Ilha de Paqueta neighborhood of Rio de
      Janeiro, Brazil. We conducted anthropometric measurements and quantitative
      ultrasound of the calcaneus using Sonost 2000 in 385 postmenopausal women. Some
      59.22% of the sample showed a T-score < -1, while 16.88% had T-score < -2.5. The
      test parameters varied with increasing age, with a statistically significant
      difference (p < 0.05) between fracture risk groups according to age, time since
      menopause, weight, BMI, and body fat. There was a correlation between sound
      velocity and BMI (r = 0.155; p = 0.002). We concluded that some 60% of the female
      study population showed some degree of fracture risk. The women at highest risk
      (T-score < -2.5) were older, with more time since menopause, and had higher
      weight and BMI as compared to the other groups.

PMID- 17221088
TI  - Waist circumference in the prediction of obesity-related adverse pregnancy
      outcomes.
AB  - The aim of this study is to evaluate the diagnostic properties of waist
      circumference in the prediction of obesity-related gestational outcomes. Pregnant
      women 20 years or older were consecutively enrolled in six Brazilian State
      capitals from 1991 to 1995. Weight, height, and waist circumference were measured
      and an oral glucose tolerance test was performed. Patients were followed through
      childbirth by chart review. Diagnostic performance for the different outcomes, as
      measured by area under the receiver operating characteristic (ROC) curve, was
      estimated through logistic regression. Areas under the ROC curve (95%CI) for
      waist circumference were 0.621(0.589-0.652) for gestational diabetes, 0.640
      (0.588-0.692) for preeclampsia, and 0.645(0.617-0.673) for macrosomia. These
      areas were similar to those for BMI (p > 0.05). A waist circumference of 82 cm
      jointly maximized sensitivity (63%) and specificity (57%). Cutoff points of 23
      kg/m(2) for pre-pregnancy BMI and 26 kg/m(2) for BMI at enrollment produced
      similar diagnostic properties. In conclusion, waist circumference predicts
      obesity-related adverse pregnancy outcomes at least as well as BMI.

PMID- 17221089
TI  - [Matrix support and reference team: a methodology for interdisciplinary health
      work management].
AB  - The authors discuss a theoretical and conceptual management methodology based on
      reference teams and matrix support. Reference team is a structural organization
      intended to combine managerial power and interdisciplinary work. Matrix support
      changes the way traditional health systems work, with specialists organically
      linked to other teams who periodically require specialized consultation. Besides
      care support, there is another goal: to build new knowledge for each health
      professional through a continuing education process. The article analyzes the
      structural, political, cultural, theoretical, and subjective obstacles to this
      new model.

PMID- 17221090
TI  - [Spatial analysis of Biomphalaria glabrata foci and human cases of mansoni
      schistosomiasis in Porto de Galinhas, Pernambuco State, Brazil, in the year
      2000].
AB  - This article provides information on the spatial distribution of schistosomiasis,
      correlating snail foci with human cases using spatial analysis. The locations
      studied were Merepe III, Pantanal, Salinas, and Soco, comprising 70% of the
      populated area of Porto de Galinhas. Malacological and parasitological surveys by
      a CPqAM/ FIOCRUZ team at the location where an epidemic occurred in 2000
      identified 15 foci of infected B. glabrata. Human cases were also diagnosed and
      recorded according to residential block. Spatial analysis was performed using the
      TerraView computer program and Kernel intensity estimation. Total infection
      rates, considering all collection stations marked out per location, varied from
      15% to 32.4%. The 15 infected B. glabrata foci included 9 in Merepe, 2 in Soco, 3
      in Salinas, and 1 in Pantanal. The results suggest a strong spatial trend in the
      risk of schistosomiais transmission in Salinas and Soco. In Merepe, with the most
      foci and where foci were closer together, individual focal infection rates were
      lower. Spatial analysis thus showed less concentration of risk as compared to
      other locations studied. As for human cases, two high-intensity areas were
      observed, shown on the map in darker colors.

PMID- 17221092
TI  - Prevalence and spatial distribution of intestinal parasitic infections in a rural
      Amazonian settlement, Acre State, Brazil.
AB  - A population-based survey of the prevalence and spatial distribution of
      intestinal parasitism was carried out in an agricultural settlement in the Amazon
      Basin of Brazil (Granada, Acre State). More than half (53.4%) of the 429 stool
      specimens from subjects in all age groups, living in 113 households, had cysts,
      ova, or larvae of intestinal parasites. The most prevalent parasites were Giardia
      duodenalis (19.6%) and soil-transmitted helminths (12.7%); 105 (24.5%) subjects
      were infected with more than one species of parasite. Significant age-related
      differences in prevalence were only found for G. duodenalis (children < 1 year
      and adults > 30 years were less affected). Six households (5.3%), situated within
      a radius of 690m, comprised 48.1% of all subjects harboring soil-transmitted
      helminths in our study area. Households within this cluster were poorer and more
      crowded than those outside the cluster. The observed spatial clustering of
      infections with soil-transmitted helminths provides valuable information for the
      spatial targeting of sanitary interventions in this area.

PMID- 17221091
TI  - Military rank and AIDS proportionate mortality in the Brazilian Navy.
AB  - This study describes AIDS mortality and occupational factors among servicemen in
      the Brazilian Navy. This is a proportional mortality study of 2,586 servicemen's
      death certificates (20-72 years of age) recorded from 1991 to 1995. Death
      certificates and occupational histories came from the Brazilian Navy Insurance
      System archives. Association was measured using proportionate mortality odds
      ratios obtained with unconditional logistic regression. AIDS proportionate
      mortality was estimated at 4.8% (n = 125) and increased during the study period,
      particularly among servicemen under 50 years of age and those with low rank. As
      compared to other occupations, there was relative excess AIDS in the "management"
      (proportionate mortality odds ratio, PMORage-adjusted = 2.45; 95%CI: 1.27-4.71),
      "secretarial" (PMORage-adjusted = 2.49; 95%CI: 1.22-5.08), and "janitorial"
      (PMORage-adjusted = 2.61; 95%CI: 1.10-6.16) occupational groups. AIDS
      proportionate mortality was higher among male than female military members.
      Higher rates were observed in some occupational groups when the members were low
      ranking. Power distribution, gender issues, and low socioeconomic status require
      further investigation using more appropriate methods.

PMID- 17221093
TI  - [Prevalence of enamel defects and the relationship to dental caries in deciduous
      and permanent dentition in Indaiatuba, Sao Paulo, Brazil].
AB  - The aim of this study was to determine the prevalence of hypoplasia, demarcated
      opacity and dental fluorosis among schoolchildren with deciduous and permanent
      dentition. The association between enamel defects and dental caries was also
      verified. The sample consisted of 624 schoolchildren aged 5 and 309 aged 12. The
      dmft and DMFT indexes were used to assess dental caries prevalence, DDE to assess
      enamel defects, and Dean to assess fluorosis. Chi-squared test was used to test
      significance (p < 0.05) and odds ratio to analyze prevalence of dental caries and
      enamel defects. A positive association between dental caries and enamel defects
      (hypoplasia, demarcated opacity and dental fluorosis) was observed for
      schoolchildren aged 5. However, only hypoplasia and demarcated opacity were
      associated with caries experience in permanent dentition. The results of this
      study indicated that children had increased odds of dental caries when enamel
      defect was present, both in deciduous and permanent dentition; further studies
      are needed to give evidence to this association.

PMID- 17221094
TI  - [Tuberculosis in Salvador, Bahia, Brazil, in the 1990s].
AB  - The characteristics of tuberculosis (TB) cases and deaths were analyzed in order
      to characterize the epidemiological profile of TB (incidence and mortality) in
      Salvador, Bahia, Brazil, in the 1990s. Annual incidence and mortality rates were
      calculated by gender, age bracket, and clinical forms of the disease using
      databases from the Tuberculosis Information System of the Bahia State Health
      Secretariat and the Mortality Information System of the Brazilian Ministry of
      Health. TB spatial distribution was analyzed according to health district. Cases
      and deaths were predominantly in males in the 15 to 39 year group. The pulmonary
      form showed the highest incidence and mortality. The existing data did not
      corroborate the hypothesis that AIDS/TB co-infection might contribute to
      maintaining the high mortality rates. The greater occurrence of tuberculosis in
      certain health districts may be associated with population density and
      unfavorable living conditions.

PMID- 17221095
TI  - [Forum: Sexual violence and health. Introduction].
AB  - This forum focuses on the health sector's response to sexual violence against
      women, analyzing the policies formulated by the Brazilian Ministry of Health and
      the protocol in two academic health centers. The premise is that an approach to
      sexual violence requires the discussion of women's autonomy in relation to their
      bodies and thus their right to abortion. This intrinsic link between sexual
      violence and morally and politically loaded issues has contributed to the
      relatively slow response by the public health sector in Brazil. However, the
      pioneering experience of two academic health centers in treating rape victims
      demonstrates the importance of these issues in the training of health
      professionals and the need to guarantee women's expanded and ongoing access to
      these services.

PMID- 17221096
TI  - [Multidisciplinary care for victims of sexual assault: the experience at the
      Federal University in Sao Paulo, Brazil].
AB  - This article discusses the importance of multidisciplinary care for victims of
      sexual assault in order to mitigate the respective physical, psychological, and
      social harm. The article begins with a brief description of the activities by
      various professionals involved in the care of victims treated at the Women's
      Health Center of the Federal University in Sao Paulo, and presents the outcome of
      some cases treated at this institution in its five years of experience. The
      article provides the socio-demographic profile of female rape victims since the
      beginning of this women's health service, with the number of women who became
      pregnant, those who underwent abortion, and the number of court suits filed.

PMID- 17221097
TI  - [Comprehensive healthcare for female victims of sexual violence: the experience
      of the Women's Comprehensive Healthcare Center, State University in Campinas,
      Brazil].
AB  - The Women's Comprehensive Healthcare Center (CAISM) has provided care for women
      who have suffered sexual violence since 1986. Since 1998, a special
      multidisciplinary team has been in charge of emergency and long-term care for
      victims of sexual violence. From August 1998 to May 2006, 1,174 women were
      treated, with an average of 150 per year in the last five years. During the same
      period, 71/109 women who became pregnant after rape had their pregnancies
      terminated, 23/109 continued the pregnancy to term, and 15/109 did not undergo
      abortion due to gestational age greater than 20 weeks. In Brazil, there are not
      enough public services to treat female victims of sexual violence who require
      legal abortion. Nationwide implementation of new services should be encouraged,
      in addition to all measures known to reduce the problem such as sex education in
      schools and widespread information and easy access to effective contraception.

PMID- 17221098
TI  - [Advances and challenges in treatment for female victims of sexual violence].
AB  - This article analyzes treatment for female victims of sexual violence, with a
      focus on partnerships between government and the organized women's movement. The
      central references are the specific literature and testimony by key social actors
      who have participated in this process. The results show that despite the real and
      symbolic importance of care for rape victims, the government and the women's
      movement have not succeeded in guaranteeing the expansion of these services or
      adequately linking the discussion of sexual violence to women's right to abortion
      under any circumstances. It is thus necessary to step up the measures on this
      agenda.

PMID- 17221099
TI  - [Forum: Sexual violence and health. Postscript].

PMID- 17221100
TI  - [Vulnerability of men who have sex with men in the context of AIDS].
AB  - The number of AIDS cases in men who have sex with men (MSM) decreased in the
      initial years of the epidemic, but the percentage of cases in this group has
      remained unaltered in the last five years. This study, aimed to improve knowledge
      on the impact of AIDS in the daily lives of MSM, was conducted in Campo Grande,
      Mato Grosso do Sul State, Brazil, using a questionnaire and interviews. The
      results show that MSM perceive their vulnerability to HIV infection, referring to
      inconsistent condom use and multiple sex partners, given that 65% of homosexuals,
      75% of bisexuals, and 33% of transvestites reported up to 5 partners in the
      previous month and emphasizing that 59% of the group reported more than 11
      partners during the same period. The susceptibility of certain groups and the
      identification and understanding of their specificities pose a major challenge in
      any geographic context where such conditions are present.

PMID- 17221102
TI  - [Fighting promise].

PMID- 17221103
TI  - [Molecular aspects of glucocorticoid sensitivity].
AB  - Glucocorticoids play an essential role in maintaining basal and stress-related
      homeostasis. Most known effects of glucocorticoids are mediated by the
      intracellular glucocorticoid receptors. The glucocorticoid sensitivity seems to
      depend on the amount of receptors expressed and the efficiency of glucocorticoid
      receptor-mediated signal transduction. Glucocorticoid resistance or
      hypersensitivity, seen in autoimmune-inflammatory diseases and in metabolic
      syndrome respectively, can represent the variability of several steps that
      influence the signaling cascade of glucocorticoid action. The recognition of
      these steps could provide the understanding of the clinical phenotype and course
      of such diseases as well as their responsiveness to glucocorticoid therapy. The
      comprehension of these pathophysiological mechanisms can also improve the
      possible therapeutic interventions. In this review, we have summarized the
      multiple factors that have been shown to be involved in this signaling cascade
      and, thus, to influence glucocorticoid sensitivity.

PMID- 17221104
TI  - [Radiosurgery for pituitary adenomas].
AB  - Pituitary adenomas represent nearly 15% of all intracranial tumors. Multimodal
      treatment includes microsurgery, medical management and radiotherapy.
      Microsurgery is the primary recommendation for nonfunctioning and most of
      functioning adenomas, except for prolactinomas that are usually managed with
      dopamine agonist drugs. However, about 30% of patients require additional
      treatment after microsurgery for recurrent or residual tumors. In these cases,
      fractionated radiation therapy has been the traditional treatment. More recently,
      radiosurgery has been established as a treatment option. Radiosurgery allows the
      delivery of prescribed dose with high precision strictly to the target and spares
      the surrounding tissues. Therefore, the risks of hypopituitarism, visual damage
      and vasculopathy are significantly lower. Furthermore, the latency of the
      radiation response after radiosurgery is substantially shorter than that of
      fractionated radiotherapy. The goal of this review is to define the efficacy,
      safety and role of radiosurgery for treatment of pituitary adenomas and to
      present the preliminary results of our institution.

PMID- 17221105
TI  - [Physiological effects of exercise training in patients with type 1 diabetes].
AB  - Insulin therapy, regular physical activity and an individualized dietary plan are
      considered to be the ideal approach for the treatment plan of type 1 diabetes
      mellitus (T1DM) patients. Clinical and experimental studies have shown the
      benefits of exercise training in T1DM, as demonstrated by insulin sensitivity
      improvement, reduction in insulin requirement and an attenuation of autonomic and
      cardiovascular dysfunction. This review explores the physiological adaptations to
      exercise training in T1DM, and discuss the guidelines for physical activity
      recommendations and prescription in this setting.

PMID- 17221106
TI  - Aspirin therapy is still underutilized among patients with type 2 diabetes.
AB  - The daily use of aspirin in patients with type 2 diabetes mellitus (DM2) reduces
      significantly cardiovascular events (CVE). In the absence of contraindications,
      American Diabetes Association (ADA) recommends the use of aspirin to all DM2
      patients older than 40 years of age. To evaluate aspirin use among 636 out
      patients with DM2 who participate in a regional multicenter study in Southern
      Brazil, a standard questionnaire was used. Patients also underwent a physical
      examination and laboratorial tests. All patients were older than 40 years (mean
      58 +/- 11 years old; 42% male) and by ADA guidelines most of them should be using
      aspirin. However, only 177 (27.5%) were on this medication. The use of aspirin
      was higher when any CVE were present. However, the percentage of users was still
      below the expected, not even reaching 50%. In conclusion, even though the use of
      aspirin is greater in patients with CVE, and its benefits are well documented, it
      is still underutilized. Strategies to enhance the use of aspirin should be
      developed to reduce the morbidity and mortality from cardiovascular diseases in
      patients with DM2.

PMID- 17221107
TI  - Tolerability and effectiveness of fluoxetine, metformin and sibutramine in
      reducing anthropometric and metabolic parameters in obese patients.
AB  - The aim of this study is to assess the effects of sibutramine (S) 15 mg/day,
      fluoxetine (F) 60 mg/day, and metformin (M) 1,700 mg/day, as an adjunct therapy
      to a 1,500 kcal/day diet, in reducing anthropometric and metabolic parameters. S
      (n= 8), F (n= 9), and M (n= 8) were compared to placebo (n= 10) in 35 obese
      patients in a 90-day trial. Side effects were also studied during the treatment.
      The data demonstrated that F therapy resulted in a greater average reduction in
      BMI (11.0%), weight (10.0%), abdominal circumference (11.0%) and %fatty-tissue
      (12.8). An elevation in HDL-cholesterol (25.8%) and a reduction in average
      triglyceride levels (28.3%) were also shown. S presented a 7.91% reduction in the
      abdominal circumference and a 9.65 reduction in %fatty-tissue was also found. M
      group presented reductions in BMI (4.03%), waist circumference (6.92%), HOMA
      (23.5%) and blood pressure (6.08% in systolic and 2.08% in diastolic). In
      general, the three drugs can be considered well tolerated. We concluded that F
      and S demonstrated a greater mean reduction in anthropometric and metabolic
      parameters when compared to M, however all of them are useful for that purpose,
      when the subjects characteristics are considered.

PMID- 17221108
TI  - [Insulin resistance and metabolic profile in lean and overweight/obese polycystic
      ovary syndrome patients].
AB  - OBJECTIVE: To evaluate insulin sensitivity and the metabolic features in normal
      weight and overweight/obese patients with PCOS. SUBJECTS AND METHODS: Forty-nine
      (49) patients from 18 to 45 years were retrospectively evaluated and divided into
      2 groups, according to the body mass index (BMI): group 1 (18.5-24.9 kg/m(2)) and
      group 2 (25-40 kg/m(2)). Collected data: systolic and diastolic blood pressure;
      fasting and after OGTT glucose, insulin and glucose/insulin ratio; area under the
      curve for glucose and insulin; HOMA-IR and HOMA-beta; lipidic profile; free (FT)
      and total testosterone (T) levels. RESULTS: Greater averages of pressoric levels,
      insulin resistance (IR) indices, triglycerides and the FT levels, in addition to
      lower HDL levels, were found in group 2. Neither correlation between the IMC with
      none of data nor of the FT and IR indices with the lipid profile were found.
      CONCLUSIONS: Obesity is associated with insulin resistance and diabetes mellitus
      in PCOS, independently on familiar history of DM. The absence of correlation
      between the IR indices and the FT with the lipidic profile suggests that other
      factors, such as the free fatty acids, can be involved in the pathogenesis of
      dyslipidemia in PCOS.

PMID- 17221109
TI  - [Centripetal distribution of body fat, overweight and cardiorespiratory fitness:
      association with insulin sensitivity and metabolic alterations].
AB  - The purpose of this paper was to investigate associations between the centripetal
      distribution of the body fat and serum lipid-lipoproteins, blood pressure and the
      index Homa-IR of insulin resistance, adjusting for indicators of overweight and
      cardiorespiratory fitness. Eighty-nine voluntaries were analyzed (44 men and 45
      women). The centripetal distribution of the body fat was analyzed through waist
      circumference (CC) and the overweight by the body mass index (BMI). The
      cardiorespiratory fitness was followed by the estimate VO(2)max by test of
      walking. After adjusted for BMI values were found significant coefficient of
      correlation between CC and levels of blood pressure and ApoB in men, and between
      CC and index Homa-IR and triglycerides in women. After adjusted for VO(2)max
      values were verified significant correlations between CC and ApoB and index Homa
      IR in men, and between CC and index Homa-IR in women. In conclusion, depending on
      the sex, the quantity and distribution of the body fat can present different
      actions in the insulin resistance and associated dysfunctions. The
      cardiorespiratory fitness per se seems not to contribute on the minimization of
      the association between the centripetal distribution of the body fat and the
      index Homa-IR; but presents a considerable impact on the association between the
      centripetal distribution of the body fat and the lipid metabolism and the levels
      of blood pressure, mainly in men.

PMID- 17221110
TI  - [Dietary assessment of the patients detected with hiperglycemia in the "Detection
      of Diabetes in Suspect Cases Campaign" in Vicosa, MG].
AB  - The purpose of this work is to assess the current, qualitative and quantitative
      alimentary consumption of patients detected with hiperglycemia in the "Detection
      of Diabetes in Suspect Cases Campaign" in Vicosa, MG. 256 patients were detected
      with hiperglycemia in 2001; however, 156 (60.9%) were assessed in 2004. The
      remaining people were dead, had changed their address, did not accept to
      participate in the study or did not have diagnosed diabetes. The hiperglycemic
      patients answered an alimentary frequency questionnaire for assessing their
      dietary intake and their usual diet recall, both previously tested in pilot
      population. The most daily consumed foods were vegetable oil (99%), bean (94%),
      rice (90%), artificial sweetener (80%), leaf vegetables (63%), milk (61%), and
      French bread (54%). Most of the patients said they avoid sugar, sugary foods and
      animal fats. The largest percentiles of nutrients inadequacy happened for energy
      (85%), fibers (87%), calcium (94%), carbohydrates (82%), monounsaturated fats
      (91%) and proteins (58%). These last three happened in relation to total energy
      intake values. The current data allowed us to know about the alimentary habits of
      these people and also to stimulate nutrition intakes, being useful to the
      nutritional counseling, suggesting specific orientations in order to provide a
      more appropriate feeding, contributing to better health conditions and well
      being.

PMID- 17221111
TI  - [Resting energy expenditure measured vs. estimated and this relationship with
      body composition in women].
AB  - OBJECTIVES: To compare the resting energy expenditure (REE, kcal/d) measured to
      the disposable equation of literature and to associate this to body composition.
      METHODS: Twenty-eight sedentary women were volunteers [weight: 79 +/- 12 kg;
      stature: 164 +/- 5 cm; age: 36 +/- 11 years; body mass index (BMI, kg/m(2)): 29
      +/- 4]. The body composition was estimated with anthropometry methods; REE was
      measured by indirect calorimetry and was estimated by the main equations of the
      literature. Equations were developed to estimate REE and the best of them was REE
      Our. RESULTS: The different time of harvest produced a similar result to REE
      measured. The Harris and Benedict, FAO/WHO/UNO only weight, and weight plus
      height, Schofield and REE-Our equations results were statistically similar to REE
      measured. The Siervo and Falconi, Schofield and Henry and Rees equations did not
      have correlation with the measured calorimetry. The best-isolated predictor of
      the REE was the body mass and the best association when adjusted to unit (kg) was
      lean body mass. The equation developed in the present work was: REE(kcal/d)=
      21837 - 14,448 * Weight(kg) + 54,963 * Lean Mass(kg)--9,341 * Stature(cm)--4,349
      * Age(years)--19753 * Body Density(g/ml). CONCLUSION: The REE prediction
      equations can prompt to errors and seem to be population specific. The best
      prediction result was with the equation developed with anthropometrics variables
      of the volunteers (measured= 1617 +/- 237 kcal/d; REE-Our= 1616 +/- 167 kcal/d).

PMID- 17221113
TI  - [Analysis on the association of physical activity with metabolic syndrome in a
      population-based study of Japanese-Brazilians].
AB  - Sedentary behavior-related diseases can be prevented by lifestyle changes. Part
      of the cardiovascular benefits of physical activity (PA) may be due to low-grade
      inflammation. This study describes the PA of a population of Japanese and
      analyses its association with metabolic syndrome (MS) adjusted a number of
      variables. This was based on a database previously created following a population
      based study of Japanese-Brazilians. 1,330 subjects aged > or = 30 years, of both
      sexes, living in Bauru, were included and they were submitted to interviews,
      being obtained sociodemographic, health, physical activity and dietary data, as
      well as clinical and laboratory data. Physical activity assessment focused on
      activities during work and leisure times. Diagnosis of MS was based on an
      adaptation of NCEP criteria for Asians. Non-conditional logistic regression had
      MS as the dependent variable. Men (46.1%) and women showed similar mean ages
      (57.0 +/- 12.8 and 56.9 +/- 12.2 years, respectively). A slight preponderance of
      females was observed. Men had a higher level of education and more frequently
      were smokers (p< 0.001); their mean values of BMI, waist and blood pressure (p<
      0.001) were higher than the womens. For both sexes, the majority referred light
      and moderate activities (81.2% of men and 86.6% of women). As far as work time is
      concerned, 87.8% of men classified their effort as light or moderate versus 96.1%
      of women. Distribution by PA levels showed that women were always less active
      than men (p= 0.01). Stratifying by the presence of MS, men and women with MS were
      significantly older and showed greater anthropometric values. Considering the
      walking duration for work, there was a tendency of shorter periods among those
      with MS (p< 0.078). As expected, subjects with MS showed significantly higher
      levels of blood pressure, plasma glucose, lipids and HOMA-IR when compared to
      those without MS. HDL levels were lower in the MS group, being significant for
      the female sex. The mean values of CRP were higher in subjects with MS. In
      logistic regression, age, BMI, HOMA-IR and CRP were shown to be independently
      associated with MS, but not parameters used to measure physical activity. Our
      findings do not allow to state that physical inactivity is associated with MS in
      a Japanese-Brazilian population. High frequencies of physical inactivity should
      have contributed to the negative findings concerning protective effects of
      physical activity. The association of MS and serum CRP favors the hypothesis that
      a low-grade inflammatory state may participate in this syndrome.

PMID- 17221112
TI  - [Evaluation of MTHFR C677T gene polymorphism and homocysteine level in coronary
      atherosclerotic disease].
AB  - OBJECTIVE: The aim of this study is to determine the prevalence of C677T
      methylenetetrahydrofolate reductase (MTHFR) polymorphism and correlate it with
      plasma homocysteine levels in coronary artery disease (CAD). METHODS: Ninety
      three patients with documented CAD from Hospital Universitario Oswaldo Cruz
      (Recife, PE, Brazil) and 108 healthy controls were evaluated. Homocysteine and
      folate levels were determined by HPLC and chemoluminescence, respectively, and
      lipid profile was considered. Genotyping was done by RFLP/PCR. RESULTS: The
      groups were homogeneous for the C677T polymorphisms. The homocysteine level in
      cases (11.7 micromol/L) was statistically different from that observed in
      controls (8.84 micromol/L, p< 0.05). It was also observed that 72% of the
      patients had homocysteine values above 12 micromol/L while the control group
      presented only 32% in this range. There was no relationship between homozygosity
      for the C677T polymorphism and the homocysteine level (p= 0.634). We noticed
      statistical differences between folate levels from patients and controls (6.22
      and 7.69 ng/dL, p< 0.05, respectively). However, there was no correlation between
      homocysteine and folate concentrations in the entire group (r= -0.202). Comparing
      cases and controls, the odds ratio (OR) when homocysteine is high and folate is
      low was OR= 11.9; CI 95%= 4.16-34.42, p< 0.01. CONCLUSION: A lack of correlation
      between C677T mutation and homocysteine level suggests that environmental factors
      and others genetic factors seem to exert more influence on homocysteine level in
      this population.

PMID- 17221114
TI  - [Polymorphism on codon 98 of the galectin-3 gene is not associated to benign and
      malignant thyroid tumors].
AB  - Galectin-3 is a multifunctional protein highly expressed in thyroid cancer. The
      galectin-3 gene (LGALS3) has several annotated candidates SNPs, however the
      relationship between galectin-3 SNPs and specific phenotypic variations relevant
      to health has not been evaluated. In this study, we investigated SNPs in the
      galectin-3 gene and a putative association with thyroid tumorigenesis. The
      presence of LGALS3 SNPs in thyroid carcinoma cell lines (NPA, TPC-1, WRO, ARO),
      thyroid tissues of 55 patients with multinodular goiter or papillary carcinoma
      diagnosis and lymphocytes of peripheral blood of 45 healthy individuals was
      evaluated by sequencing and SSCP. The analysis of LGALS3 coding sequence showed
      that the T98P site presents a great genotypic variation, since we observed both
      homozygous (AA or CC) and heterozygous (AC) patterns. In thyroid carcinoma cell
      lines, the genotype of NPA in the LGALS3 T98P site is CC, while TPC-1, WRO and
      ARO are AC. The genotypic frequency of T98P SNP observed in multinodular goiter
      (AC= 67%; AA= 23%; CC= 10%) and papillary carcinoma (AC= 68%; AA= 20%; CC= 12%)
      were similar to the frequency observed in the control population (AC= 60%, AA=
      24%, CC= 16%). In conclusion, no association between LGALS3 T98P genotype and the
      phenotype of the benign or malignant thyroid tumor was observed.

PMID- 17221115
TI  - [Divergent responses of serum testosterone and cortisol in athlete men after a
      marathon race].
AB  - Physical exercise alters homeostasis, as it requires prompt mobilization of
      metabolic sources. In this study, we measured serum testosterone (T) and cortisol
      (C) levels and the muscle-wastage enzymes CK, CKMB and LDH in 20 healthy male
      athletes (ages 25 to 40 years) in response to a marathon race (42.2 km). Venous
      blood samples were drawn in 3 different periods: (i) in the morning, 48 h before
      the competition (control), (ii) at the end of the race (end), and (iii) in the
      next morning, 20 h after the race (recovery). At the end, T was significantly
      lower (from 673 to 303 ng/dl) and C higher (from 20.3 to 42.5 microg/dl) as
      compared to the control period. At recovery, both were virtually identical to
      control levels. CK, CKMB and LDH were significantly higher at the end of the
      competition and even higher in the recovering period (except for CKMB),
      characterizing muscle wastage. CK and LDH disclosed a significant negative
      correlation with T (-0.412 and -0.546, respectively), whereas CKMB correlated
      positively with C (0.4521). We conclude that the inverse correlation observed
      between T and C levels, and the pattern of CK, CKMB and LDH increase, allow us to
      confirm that a marathon race may cause a marked physical stress, resulting in a
      distinct hormonal imbalance and severe cellular damage.

PMID- 17221117
TI  - [Clinical treatment with anti-thyroid drugs or iodine-131 therapy to control the
      hyperthyroidism of graves disease: a cost-effectiveness analysis].
AB  - In this study, we set out to evaluate the costs and effectiveness of the 2 most
      used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a
      mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women,
      mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving
      ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI
      group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate
      the costs of each therapy, we analyzed the number of visits during this period,
      the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The
      group treated only with ATD needed a higher number of visits and laboratory
      measurements, with the mean total cost of R dollars 1,345.81, while the RAI group
      spent a mean amount of R dollars 622.94. Therefore, the costs of the RAI
      treatment were 53.5% lower than clinical therapy with ATD. The present study
      demonstrates that RAI treatment has a lower cost than ATD, being very effective
      in controlling the hyperthyroidism of Graves disease.

PMID- 17221116
TI  - [The effect of propylthiouracil on the efficacy of radioiodine (I-131) therapy in
      graves hyperthyroidism].
AB  - Aiming at evaluating the effect of antithyroid drugs on the efficacy of
      radioiodine treatment (RAI) we retrospectively analyzed 226 patients with Graves
      disease hyperthyroidism submitted to RAI between 1990 and 2001: 58 patients
      without any antithyroid drug (ATD) prior to RAI, 119 patients using
      propylthiouracil (PTU) and 49 patients using methimazole (MMI) prior to RAI.
      Clinical and laboratory parameters 1 year after RAI defined their clinical status
      (cured or not cured). High serum free T4 and 131-iodine uptake were negatively
      related with cure as well as lower RAI doses (mCi) and larger goiters (p< 0.05).
      The percentage of cured patients on PTU prior to RAI was 70.2% (84/119), while
      those on MMI was 85.7% (42/49), and 84.5% (49/58) of those without ATD prior to
      RAI (p= 0.034). On logistic regression analysis, free T4 > 4 ng/dl, large goiter,
      RAI dose < 10 mCi and PTU prior to RAI were related to lower cure rates. Compared
      to patients with no ATD prior to RAI, we concluded that the previous use of PTU
      implies in higher failure rates after RAI (OR= 3.13), an effect not observed in
      patients on MMI (OR= 1.28).

PMID- 17221118
TI  - [MicroRNAs: novel class of gene regulators involved in endocrine function and
      cancer].
AB  - MicroRNAs (miRNAs) represent a novel class of endogenous approximately 22
      nucleotide RNAs that negatively regulate gene expression by inhibiting
      translation of target RNAs. Discovered just over a decade ago in Caenorhabditis
      elegans, miRNAs are now recognized as one of the major regulatory gene families
      in plants and animals. In the human genome, 462 miRNA genes have been discovered
      and the estimated number of miRNAs is as high as 1000. Bioinformatics analysis
      indicated that a unique miRNA acts on several mRNA, influencing multiple
      signaling pathways concomitantly, thus presenting enormous regulatory potential.
      Although the biology of miRNAs is not well understood, recent evidences have
      linked these molecules to diverse biological processes. Moreover, aberrant
      expression of miRNAs has been associated to human disease, including that related
      to the endocrine system and cancer.

PMID- 17221119
TI  - [Hirsutism: differential diagnosis].
AB  - Hirsutism is one of the manifestations of the hyperandrogenic syndromes. A
      practical approach consists of dividing the hyperandrogenic syndromes into
      virilizing and non-virilizing, in accordance to the presence or absence of
      virilization symptoms. A case of a patient with hirsutism and a high basal and
      post-ACTH stimulation concentration of 17-OHP is presented. The absence of
      virilization and of clinical history discarded as etiology the virilizing
      neoplasias and hyperthecose of the ovary. Among the causes of non-virilizing
      syndromes, the presence of the menstrual disturbance and hyperandrogenemia
      discarded idiopathic hirsutism. In accordance to the Consensus of Rotterdam, the
      diagnosis of polycystic ovary syndrome was considered. For to exclude the non
      classic form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency,
      the patient was submitted to a short ACTH-(1-24) stimulation test. The 17-OHP
      concentrations after stimuli were 14 ng/dL, being that, in the dependence of the
      limit of considered cut-off, it would be compatible with this illness. Although
      the promoter region had not been studied, we can consider that this diagnosis was
      excluded through the sequencing of CYP21A2 gene, since mutation on the promoter
      region is a rare event.

PMID- 17221120
TI  - [Localized granuloma annulare in patient with graves hyperthyroidism: case
      report].
AB  - Granuloma annulare (GA) is a begin dermatosis characterized, in general, for
      papular lesions with annular configuration. Its clinical forms comprehend
      localized GA, generalized GA, perforating GA and subcutaneous GA. With unknown
      etiology many factors have been responsible, including autoimmune diseases. We
      describe a case of a 45-year-old man, with characteristic dermatological injuries
      of localized GA, associated to systemic alterations, compatible with
      hyperthyroidism (Graves disease). The patient was submitted to an endocrine and
      dermatological treatment with control of the clinical state. The unusual
      association of localized GA with hyperthyroidism, not found in the medical
      literature, stimulated us to publish the case.

PMID- 17221121
TI  - [Pituitary abscess simulating apoplexy].
AB  - A pituitary abscess is a rare pathology, but it must be considered when
      evaluating sellar masses, since its prognosis depends on surgical drainage and on
      the use of specific antibiotics. The main clinical manifestation is chronic
      headache, and it is not always associated with the identification of a site of
      infection, which diminishes the probability of including it in diagnostic
      hypotheses. The case is presented of a patient with a pituitary abscess and a
      previous history of adenoma that had been operated on, recent onset headache and
      acquired hypopituitarism whose initial diagnosis was pituitary apoplexy.

PMID- 17221122
TI  - [Case report: recently diagnosed celiac disease as aggravating factor of
      osteoporosis in an old woman].
AB  - Sixty-three-year-old woman requested medical attention for osteoporosis. Bone
      densitometry revealed: T(spine (L1-L4))= -3.5 SD [Bone mineral density (BMD):
      0.766 g/cm(2)]. T(femoral neck) = -2.4 SD (BMD: 0.716 g/cm(2)). She has been in
      calcium and vitamin D supplementation for 2 years. She informed a 5-year-history
      of hypothyroidism in levothyroxine replacement. Alendronate sodium 70 mg/week was
      initiated with significant increase in BMD in the first year (6.1% equally in
      spine and femoral neck). After a 5-year follow-up, the patient presented with
      weight loss, anemia and decrease in BMD (12.6% in spine and 20.9% in femoral
      neck). Clinical history revealed intermittent diarrhea episodes for 2 years and
      the hypothesis of celiac disease was suspected. Anti-gliadin and anti-endomysium
      antibodies were positive: 25.3 U/mL (< 20) e 1/5 U/mL (RV: negative),
      respectively. Bone biochemical parameters revealed normal levels of calcium and
      phosphate, increased parathyroid hormone: 283 pg/mL (10-65) and increased levels
      of bone reabsortion markers, consistent with secondary hyperparathyroidism in
      response to malabsorptive syndrome. One year after gluten-free diet, patient
      improved of malabsorptive symptoms and gained BMD (47.3% in spine and 31.6% in
      femoral neck), confirming the hypothesis of celiac disease as aggravating factor
      of osteoporosis in this patient.

PMID- 17221124
TI  - [The metabolic syndrome and psychiatric disorders: an association that cannot be
      forgotten].

PMID- 17221123
TI  - [Cerebral calcifications due to hypoparathyroidism: considerations about cases
      diagnosed many years after partial thyroidectomy].
AB  - The diagnosis of hypoparathyroidism with neurological findings occurring years
      after thyroid surgery is considered to be rare. The authors describe 3 cases of
      hypoparathyroidism associated to brain calcifications diagnosed many years after
      partial thyroidectomy. Two patients were admitted to Emergency Services
      presenting with seizures, without a previous diagnosis of hypoparathyroidism. The
      diagnosis was suspected adding the biochemical analysis to the scar on the neck.
      The CT, which was performed more than 20 years after surgery, showed large
      cerebral calcifications in both cases. The third patient did not have
      neurological symptoms, but presented basal and cerebellar calcifications that
      were demonstrated in the CT. All patients were treated with calcium and vitamin D
      with great improvement of clinical status. Adding to a case published previously,
      we count 4 cases from the same region. Thyroidectomies were very common in this
      region poor in dietary iodide. Since the clinical follow up was inadequate, we
      suspect that undetected cases similar to these may exist in the present moment.

PMID- 17221125
TI  - Survey of chicken abattoir for the presence of Campylobacter jejuni and
      Campylobacter coli.
AB  - The genus Campylobacter is of great importance to public health because it
      includes several species that may cause diarrhea. These species may be found in
      water, food and in the intestinal tract of chickens. This study investigated the
      presence of Campylobacter jejuni and Campylobacter coli in chicken abattoirs in
      Sao Paulo State, Brazil. A total of 288 samples of feces, feathers, scald water,
      evisceration water, chiller water, and the rinse water of eviscerated, not
      eviscerated and chilled carcasses were collected in six chicken abattoirs.
      Polymerase Chain Reaction (PCR) was performed in Campylobacter spp.-positive
      isolates using the gene HIP, specific for hippuricase enzyme from Campylobacter
      jejuni and aspartokinase gene, specific to detect Campylobacter coli. The
      percentage of positive isolates of Campylobacter jejuni was 4.9% (14/288).
      Isolation was greater in feces samples (22%, 8/36). One sample was positive for
      the species C. coli. In conclusion, the results indicate that it is necessary to
      improve quality control for Campylobacter spp. in chicken abattoirs.

PMID- 17221126
TI  - An evaluation of manual and mechanical methods to identify Candida spp. from
      human and animal sources.
AB  - To compare two yeast identification methods, i. e, the manual and the VITEK
      mechanical methods, 62 clinical samples from hemocultures and animal sources were
      analyzed. After identification as Candida yeasts by the VITEK method, the strains
      were recharacterized using manual assimilation methods and sugar fermentation
      tests. Our findings reveal 58% concurrent identification between the two methods
      for animal strains, and 51% for human hemoculture strains.

PMID- 17221127
TI  - Frequency of soil contamination by Toxocara canis eggs in the south region of Sao
      Paulo municipality (SP, Brazil) in a 18 month period.
AB  - Soil contamination by embryonic eggs of Toxocara canis is the main source of
      human infection by this ascarid larvae resulting, sometimes, in the occurrence of
      visceral larva migrans syndrome. The objective of the present research is to
      determine the frequency of T. canis eggs in soil samples monthly collected in
      nine public places, located at the South Region of Sao Paulo municipality in a 18
      month period, from February 2004 to July 2005. The soil samples collected were
      treated with a 30% antiformine solution and with a sodium dichromate solution (d
      = 1.40) and microscopic slides were prepared and examined under light microscopy
      for searching T. canis eggs. Two peaks of higher frequency had been found, one in
      February-May 2004 and the other in April-July 2005.

PMID- 17221128
TI  - Serological markers and risk factors for hepatitis B and C viruses in patients
      infected with human immunodeficiency virus.
AB  - Both hepatitis B and hepatitis C viruses (HBV and HCV) infection are common in
      HIV-infected individuals as a result of shared risk factors for acquisition. A
      serological study for HBV and HCV was performed in 251 HIV-positive individuals
      from Medellin, Colombia. A qualitative RT-PCR for HCV was done in 90 patients
      with CD4+ T-cell count < 150 per mm(3). Serological markers for HBV infection
      were present in 97 (38.6%) patients. Thirty six of them (37.1%) had isolated anti
      HBc. A multivariate analysis indicated that the following risk factors were
      significantly associated with the presence of these markers: age (OR = 1.05, 95%
      CI: 1.01-1.08), pediculosis pubis (OR = 1.83, 95% CI: 1.01-3.33), men who have
      sex with men and women (OR = 3.23, 95% CI: 1.46-7.13) and men who have sex only
      with men (OR = 3.73, 95% CI: 1.58-8.78). The same analysis restricted to women
      showed syphilis as the only significant risk factor. Thus, HBV infection was
      considerably associated with high risk sexual behavior. HCV was present in only
      two (0.8%) of HIV patients. Both of them were positive by RT-PCR and anti-HCV.
      This low frequency of HIV/HCV coinfection was probably due to the uncommon
      intravenous drug abuse in this population. The frequent finding of isolated anti
      HBc warrants molecular approaches to rule out the presence of cryptic HBV
      infection.

PMID- 17221129
TI  - Sharing of antigens between Plasmodium falciparum and Anopheles albimanus.
AB  - The presence of common antigens between Plasmodium falciparum and Anopheles
      albimanus was demonstrated. Different groups of rabbits were immunized with:
      crude extract from female An. albimanus (EAaF), red blood cells infected with
      Plasmodium falciparum (EPfs), and the SPf66 synthetic malaria vaccine. The
      rabbit's polyclonal antibodies were evaluated by ELISA, Multiple Antigen Blot
      Assay (MABA), and immunoblotting. All extracts were immunogenic in rabbits
      according to these three techniques, when they were evaluated against the
      homologous antigens. Ten molecules were identified in female mosquitoes and also
      in P. falciparum antigens by the autologous sera. The electrophoretic pattern by
      SDS-PAGE was different for the three antigens evaluated. Cross-reactions between
      An. albimanus and P. falciparum were found by ELISA, MABA, and immunoblotting.
      Anti-P. falciparum and anti-SPf66 antibodies recognized ten and five components
      in the EAaF crude extract, respectively. Likewise, immune sera against female An.
      albimanus identified four molecules in the P. falciparum extract antigen. As far
      as we know, this is the first work that demonstrates shared antigens between
      anophelines and malaria parasites. This finding could be useful for diagnosis,
      vaccines, and the study of physiology of the immune response to malaria.

PMID- 17221130
TI  - Adrenal function in 23 children with paracoccidioidomycosis.
AB  - Adrenal involvement by Paracoccidioides brasiliensis was described at necropsies
      and in many clinical studies, but only in adults. Therefore, the aim of this
      study was to evaluate adrenal function in children with paracoccidioidomycosis.
      Twenty-three children with the systemic form of paracoccidioidomycosis were
      evaluated and divided in two Groups: Group A (n = 8) included children before
      treatment and Group B (n = 15) children after the end of treatment. Plasma
      cortisol (basal and after ACTH test), ACTH, renin activity, aldosterone, sodium
      and potassium were measured. They were within normal range in all cases, except
      for renin activity and aldosterone, which were elevated in some cases. Group A
      patients showed basal and post-ACTH cortisol levels significantly greater than
      Group B patients. The results showed that adrenal function was not compromised in
      these children with paracoccidioidomycosis.

PMID- 17221131
TI  - Kinetics of growth of Leishmania (Leishmania) chagasi cycle in McCoy cell
      culture.
AB  - The kinetics of growth of Leishmania performed in vitro after internalization of
      the promastigote form in the cell and the occurrence of the transformation of the
      parasite into the amastigote form have been described by several authors. They
      used explants of macrophages in hamster spleen cell culture or in a human
      macrophage lineage cell, the U937. Using microscopy, the description of
      morphologic inter-relationship and the analysis of the production of specific
      molecules, it has been possible to define some of the peculiarities of the
      biology of the parasite. The present study shows the growth cycle of Leishmania
      chagasi during the observation of kinetic analysis undertaken with a McCoy cell
      lineage that lasted for a period of 144 hours. During the process, the
      morphologic transformation was revealed by indirect immunofluorescence (IF) and
      the molecules liberated in the extra cellular medium were observed by SDS-PAGE at
      24-hour intervals during the whole 144-hour period. It was observed that in the
      first 72 hours the promastigote form of L. chagasi adhered to the cell membranes
      and assumed a rounded (amastigote-like) form. At 96 hours the infected cells
      showed morphologic alterations; at 120 hours the cells had liberated soluble
      fluorescent antigens into the extra cellular medium. At 144 hours, new elongated
      forms of the parasites, similar to promastigotes, were observed. In the SDS-PAGE,
      specific molecular weight proteins were observed at each point of the kinetic
      analysis showing that the McCoy cell imitates the macrophage and may be
      considered a useful model for the study of the infection of the Leishmania/cell
      binomial.

PMID- 17221132
TI  - Serodiagnosis of neurocysticercosis in patients with epileptic seizure using
      ELISA and immunoblot assay.
AB  - Sera from 88 patients from Santa Catarina and Sao Paulo states of Brazil, with
      epileptic seizures who underwent cerebral computed tomography (CT) were analyzed
      for the detection of antibodies to T. solium cysticercus by ELISA and Immunoblot
      (IB) with the following antigens: Taenia solium cysticercus total saline (Tso),
      Taenia crassiceps cysticercus vesicular fluid (Tcra-vf) and T. crassiceps
      cysticercus glycoproteins (Tcra-gp). ELISA carried out with Tso, Tcra-vf and Tcra
      gp antigens showed 95%, 90% and 80% sensitivities, respectively, and 68%, 85% and
      93% specificities, respectively. In the epileptic patients group, ELISA
      positivity was 30%, 51% and 35% with Tso, Tcra-vf and Tcra-gp antigens
      respectively. Considering the IB as the confirmatory test, the positivity was 16%
      (14/88) in the epileptic patients total group and 22% (12/54) in the epileptic
      patients with positive CT and signals of cysticercosis. We found a significant
      statistical correlation among ELISA or IB results and the phase of the disease
      when any antigens were used (p < 0.05). We emphasize the need to introduce in the
      laboratory routine the search for neurocysticercosis (NC) in patients presenting
      with epileptic seizures because of the high risk of acquiring NC in our region
      and its potential cause of epilepsy.

PMID- 17221133
TI  - Methylene blue vital staining for Trypanosoma cruzi trypomastigotes and
      epimastigotes.
AB  - The morphological identification of Trypanosoma cruzi is currently considered to
      have a high specificity, but its sensitivity, which depends on the volume of the
      sample examined, is rather low. Trypanosome developmental stages suspended in
      blood, reduviid feces, and culture media are routinely searched for by means of
      fresh film examination (about 2 microL). High speed centrifugation of blood
      samples separates the buffy coat, where most trypomastigotes concentrate. As the
      parasites are transparent and colorless, their detection is mostly dependent on
      their motility. The fluorescent vital stain acridine orange has been used to
      enhance image contrast, as exemplified by the QBC (Quantitative Buffy Coat)
      technique. Staining blood, buffy coat, reduviid feces, and culture media samples
      with methylene blue (also a vital dye) is a means of producing sharp, well
      contrasted images of motile or non-motile T. cruzi developmental stages, only
      standard laboratory microscopes being required. Slides previously coated with a
      thin layer of methylene blue are used to stain fresh blood films.
      Photomicrographs exemplify the results of methylene blue staining applied to
      living and fixed parasites.

PMID- 17221134
TI  - Microsporidiosis in a Brazilian University Hospital: case report.
AB  - This is the report on a patient with chronic diarrhea caused by microsporidia. He
      is married, infected with HIV and has low CD4 cell count. The diagnosis was
      established through stool parasite search using concentration methods and Gram
      chromotrope staining technique. Ileum biopsy was also performed in this case. The
      etiological diagnosis may be established in a clinical laboratory, by chromotrope
      staining technique in routine microscopic examination of stool specimens.

PMID- 17221135
TI  - Disseminated cutaneous cryptococcosis in a patient with AIDS.
AB  - The authors study a patient carrying AIDS, with exuberant dermatological
      manifestations of cryptococcosis. They stress the therapeutic effectiveness of
      short-term amphotericin B. The authors reviewed cases of cutaneous infection with
      Cryptococcus reported in the national and international literature, verifying
      that the frequency has increased with the AIDS epidemic. Also, they discuss about
      the differential diagnosis with some cases of dermatosis, particularly with the
      disseminated giant molluscum contagiosum. In relation to the therapy, they affirm
      that the choice of drug depends on the organ involved, as well as the immune
      state of the patient.

PMID- 17221136
TI  - Toxoplasma gondii genotyping in a dog co-infected with distemper virus and
      ehrlichiosis rickettsia.
AB  - This paper reports a toxoplasmosis, ehrlichiosis and distemper co-infection in a
      dog with an exuberant neuropathological clinical picture. Primary involvement was
      discussed based on information collected in the analysis of the clinical case,
      such as neurological impairment, epidemiological data, poor immunoprophylactic
      scheme of the dog affected and the role of these diseases on immunosuppression.
      Canine distemper and ehrlichiosis were diagnosed based on epidemiologic data,
      clinical signs, hematological and cytological evaluation. Toxoplasma gondii was
      isolated and genetically characterized as Type I using restriction analysis
      (RFLP) with SAG-2 genes. Immunosuppression features of both dogs and human beings
      are discussed, as well as implications on animal and public health. This is the
      first report on toxoplasmosis, ehrlichiosis and distemper co-infection in a dog
      in Brazil, associated with genotyping determination of the T. gondii strain
      involved.

PMID- 17221137
TI  - Acholeplasma laidlawii PG8 culture adapted to unfavorable growth conditions shows
      an expressed phytopathogenicity.
AB  - Mycoplasmas are the smallest, self-replicating, prokaryotic organisms with avid
      biochemical potential and spreading in higher eukaryotes in nature. In this
      study, Acholeplasma laidlawii PG8 cells were cultivated on a deficient medium for
      480 days resulting in a mycoplasma culture that was adapted in vitro to
      unfavorable growth conditions. Cells that survive this condition had decreased
      sizes (about 0.2 microm) and increased phytopathogenicity. This resulted in more
      frequent appearance of various morphological alterations when plants of vinca
      (Vinca minor L.) were infected by adapted mycoplasma cells. The increasing
      pathogenicity was accompanied by changes in genome expression in these adapted
      cells. Further studies are needed to explore the exact mechanisms that permit
      adaptation to unfavorable growth conditions and changes in phytopathogenic
      potential.

PMID- 17221138
TI  - Quality physical intervention activity for persons with Down syndrome.
AB  - Persons with Down syndrome (DS) are at risk for a life of inactivity that can
      result in a multitude of medical problems including heart and vascular diseases.
      This review presents findings regarding the physical status of individuals with
      DS, as well as proper interventions found to improve the physical fitness and
      general health for this population. This review was written with the intent to
      suggest practical directions in planning and implementing quality physical
      intervention programs for this population.

PMID- 17221139
TI  - Therapy for children with henoch-schonlein purpura nephritis: a systematic
      review.
AB  - Although severe kidney involvement in children with Henoch-Shonlein purpura (HSP)
      is rarer than that in adults, morbidity should not be underevaluated and follow
      up is mandatory. Some drugs are introduced as well-defined treatment options,
      others can be promising therapeutic alternatives. Therapy of HSP nephritis in
      children can range from simply steroids to combined immunosuppressant treatments.
      The prophylactic treatment for renal complication of patients with HSP has been
      sometimes suggested, but with conflicting results and ultimately not clearly
      proven. The treatment of overt HSP nephritis includes steroids and other
      immunosuppressant drugs. Methylprednisolone pulse therapy and prednisone per os
      are tested drugs. These steroids could be used in combination with other
      immunosuppressant drugs, such as cyclosporin A and cyclophosphamide.
      Unfortunately, of these two drugs, only cyclophosphamide is demonstrated as
      effective in a recent randomized controlled trial. However, since there are
      insufficient data and unstructured study designs, ACE-I, azathioprine,
      mycophenolate mofetil, and urokinase need to be more tested in childhood HSP
      nephritis. In addition to drugs, other techniques are used to treat the severe
      form of nephritis. Of these, in a multicenter study, plasmapheresis demonstrated
      efficacy in delaying the progression of kidney disease. However, no convincing
      studies have been made to date concerning either intravenous immunoglobulin,
      factor XIII administration, antioxidant vitamin E, and fish oil to treat HSP
      nephritis.

PMID- 17221140
TI  - Mechanisms of action of probiotics in intestinal diseases.
AB  - Intestinal microbiota is a positive health asset that exerts a conditioning
      effect on intestinal homeostasis. Resident bacteria deliver regulatory signals to
      the epithelium and instruct mucosal immune responses. Recent research has
      revealed a potential therapeutic role for the manipulation of the microbiota and
      exploitation of host-microbial signalling pathways in the maintenance of human
      health and treatment of various mucosal disorders. A variety of pharmabiotic
      strategies, such as the use of specific members of the microbiota, their surface
      components, or metabolites, as well as genetically modified commensal bacteria,
      are being investigated for their ability to enhance the beneficial components of
      the microbiota. It is clear that engagement with host cells is central to
      pharmabiotic action, and several strain-specific mechanisms of action have been
      elucidated. However, the molecular details underpinning these mechanisms remain
      almost entirely unknown. Understanding how pharmabiotics exert their beneficial
      effects is critical for the establishment of definitive selection criteria for
      certain pharmabiotic strategies for specific clinical conditions. Scientifically
      accredited evidence of efficacy and studies to elucidate the molecular mechanisms
      of host-microbiota interactions are needed to lend credence to the use of
      pharmabiotic strategies in clinical medicine.

PMID- 17221141
TI  - Reasons why medicines are returned to Swedish pharmacies unused.
AB  - OBJECTIVE: To identify the reasons and their relative importance why medicines
      are returned to Swedish pharmacies unused. SETTING: A random sample of the
      pharmacies in Sweden. METHOD: Interviews using a semi-structured interview form
      with pharmacy customers returning unused medicines to the pharmacy. MAIN OUTCOME
      MEASURE: Reasons given by patients/relatives/carers for returning unused
      medicines to the pharmacy. RESULTS: The four main reasons for returning unused
      medicines to the pharmacy were: (1) the medicines were too old, (2) the user had
      died, (3) there was no need for the medicine anymore, and (4) therapy changes.
      These reasons made up 75% of all reported reasons. CONCLUSION: Hoarding or over
      supply of prescribed medicines may explain a large part of the volume of
      medicines that remain unused. Actions aiming to reduce waste of prescribed
      medicines ought to focus on those patients who contribute to a substantial part
      of all unused medicines.

PMID- 17221143
TI  - Vigabatrin, a GABA transaminase inhibitor, reversibly eliminates tinnitus in an
      animal model.
AB  - Animal models have facilitated basic neuroscience research investigating the
      pathophysiology of tinnitus. It has been hypothesized that partial
      deafferentation produces a loss of tonic inhibition in the auditory system that
      may lead to inappropriate neuroplastic changes eventually expressed as tinnitus.
      The pathological down-regulation of gamma-amino butyric acid (GABA) provides a
      potential mechanism for this loss of inhibition. Using an animal model previously
      demonstrated to be sensitive to treatments that either induce or attenuate
      tinnitus, the present study examined the effect of the specific GABA agonist
      vigabatrin on chronic tinnitus. It was hypothesized that vigabatrin would
      decrease the evidence of tinnitus by restoring central inhibitory function
      through increased GABA availability. Vigabatrin has been demonstrated to elevate
      central GABA levels (Mattson et al. 1995). Tinnitus was induced in rats using a
      single 1-h unilateral exposure to band-limited noise, which preserved normal
      hearing in one ear. Psychophysical evidence of tinnitus was obtained using a free
      operant conditioned-suppression method: Rats lever-pressed for food pellets and
      were trained to discriminate between the presence and absence of sound by
      punishing lever pressing with a mild foot shock (0.5 mA; 1 s) at the conclusion
      of randomly introduced silent periods (60 s) inserted into background low-level
      noise. Additional random insertion of pure tone and noise periods of variable
      intensity enabled the derivation of psychophysical functions that reflected the
      presence of tinnitus with features similar to 20-kHz tones. Vigabatrin was
      chronically administered via drinking water at 30 and 81 mg kg-1 day-1, with each
      dose level tested over 2 weeks, followed by a 0-mg washout test. Vigabatrin
      completely and reversibly eliminated the psychophysical evidence of tinnitus at
      both doses. Although vigabatrin has serious negative side effects that have
      prevented its clinical use in the USA, it is nevertheless a potentially useful
      tool in unraveling tinnitus pathophysiology.

PMID- 17221144
TI  - A dual-process integrator-resonator model of the electrically stimulated human
      auditory nerve.
AB  - A phenomenological dual-process model of the electrically stimulated human
      auditory nerve is presented and compared to threshold and loudness data from
      cochlear implant users. The auditory nerve is modeled as two parallel processes
      derived from linearized equations of conductance-based models. The first process
      is an integrator, which dominates stimulation for short-phase duration biphasic
      pulses and high-frequency sinusoidal stimuli. It has a relatively short time
      constant (0.094 ms) arising from the passive properties of the membrane. The
      second process is a resonator, which induces nonmonotonic functions of threshold
      vs frequency with minima around 80 Hz. The ion channel responsible for this trend
      has a relatively large relaxation time constant of about 1 ms. Membrane noise is
      modeled as a Gaussian noise, and loudness sensation is assumed to relate to the
      probability of firing of a neuron during a 20-ms rectangular window. Experimental
      psychophysical results obtained in seven previously published studies can be
      interpreted with this model. The model also provides a physiologically based
      account of the nonmonotonic threshold vs frequency functions observed in biphasic
      and sinusoidal stimulation, the large threshold decrease obtained with biphasic
      pulses having a relatively long inter-phase gap and the effects of asymmetric
      pulses.

PMID- 17221145
TI  - Reflex sympathetic dystrophy: a retrospective epidemiological study of 168
      patients.
AB  - This is a retrospective epidemiological study. The objective is to determine the
      epidemiological characteristics including the patient demographics, etiological
      factors, duration of symptoms, treatment modalities applied and clinical outcome
      of the treatment in reflex sympathetic dystrophy (RSD). Medical records of the
      168 patients managed in two tertiary hospitals with the diagnosis of RSD that was
      made according to both IASP criteria and three-phase bone scan were reviewed. The
      upper limb was affected 1.5 times as commonly as the lower limb. Of the 168
      cases, 10.7% were non-traumatic. In 89.3% of the patients, RSD developed after a
      traumatic inciting event with a predominance of fracture. In 75.6% of the
      patients, RSD developed due to job-related injuries. The percentage of successful
      clinical outcome was 72%. The percentage of the patients that did not respond to
      therapy was 28%. The management period is long and this causes higher therapeutic
      costs in addition to loss of productive effort. However, response to therapy is
      good. On the other hand, in approximately one third of the patients, RSD does not
      improve despite all therapeutic interventions. In addition to compensation costs,
      this potentially debilitating feature causes RSD to appear as a socioeconomic
      problem.

PMID- 17221146
TI  - Efficacy prediction of cevimeline in patients with Sjogren's syndrome.
AB  - The objective of this study was to examine the clinical and immunological factors
      influencing the efficacy of cevimeline hydrochloride hydrate (cevimeline) for the
      treatment of xerostomia in patients with Sjogren's syndrome (SS). Thirty primary
      SS patients who were medicated with cevimeline were enrolled in this study. Whole
      stimulated sialometry (WSS) was compared between pre- and posttreatment points (4
      weeks after oral cevimeline administration) and the increment rate of WSS was
      calculated. Multiple regression was employed to examine the relative
      contributions of the clinical and immunological factors, including age,
      pretreatment WSS, duration of disease, sialography, minor salivary gland biopsy,
      anti-Ro/SS-A antibodies, anti-La/SS-B antibodies, and antibodies to muscarinic
      type 3 receptors to the posttreatment WSS. Patients with normal sialography
      findings, negative minor salivary gland biopsy, and absence of anti-La/SS-B
      antibodies had significantly higher increment rates of WSS compared with those
      with positive findings (p=0.042, 0.002, and 0.018, respectively). Results of the
      multiple regression analysis showed that sialography (coefficient=-0.867,
      p=0.004) and minor salivary gland biopsy (coefficient=-0.869, p=0.003) had
      significant associations with the posttreatment WSS. Our preliminary results
      demonstrated the relationship between the effect of cevimeline on saliva
      secretion and the degree of salivary gland destruction evaluated by sialography
      and histopathological findings in the labial minor salivary glands. These
      diagnostic approaches could provide useful prognostic information on the efficacy
      of cevimeline in SS patients.

PMID- 17221147
TI  - External iliac artery injury during insertion of tension-free vaginal tape: a
      case report and literature review.
AB  - Although rare, serious vascular injuries after tension-free vaginal tape (TVT)
      insertion have been well known. We present a case of external iliac artery injury
      after TVT insertion, managed successfully by surgical intervention. This article
      also reviews the literature regarding major vascular injuries and their
      management. We conclude that clinicians should be able to suspect rare but
      serious vascular injuries, and patients have to be fully counselled regarding
      their potential consequences.

PMID- 17221148
TI  - A radiological study on the anatomical proximity of the ureters and the cervix.
AB  - In order to evaluate risk factors for anatomical proximity between the cervix and
      the ureters the distance between the ureters and the cervix was measured in 499
      computerized tomography (CT) studies at the most dorsal reflection of the
      ureters. The relationship between the ureter-cervical distance and the presence
      of pelvic pathology was assessed by correlation tests and regression analysis. Of
      the 499 CT studies, 252 demonstrated radiographic pathologies. Among abnormal
      scans, 126 (50%) involved cervical pathology. At least one ureter was within 0.5
      cm of the cervix in 3.6% of patients with normal CT scans and in 10.3% of
      patients with cervical pathology. Overall, the right ureter was significantly
      closer to the cervix than the left (2.0 +/- -0.8 cm vs. 2.2 +/- 1.0 cm, p <
      0.05). In cases were the pathology was limited to the cervix, the right ureter
      was more distant than the left (2.0 +/- 0.6 cm vs. 1.7 +/- 0.6 cm, p < 0.05). The
      distance between the ureters and the cervix was inversely correlated with the
      lateral diameter of the cervix (r = 0.18, p < 0.001) and its anterior-posterior
      diameter (r = 0.11, p < 0.001). Age did not correlate with the distance of the
      ureters from the cervix (r = 0.002, p = N.S). In conclusion, approximately 10% of
      patients with cervical pathology can be expected to have a ureter proximate less
      than 5 mm from the cervix. For patients with cervical pathology undergoing a
      planned hysterectomy, preoperative measurement of cervical-ureteric distance may
      be warranted. In these circumstances intra-operative measures to protect the
      ureter and ascertain its integrity may be invaluable.

PMID- 17221149
TI  - Translabial ultrasound assessment of the anal sphincter complex: normal
      measurements of the internal and external anal sphincters at the proximal, mid-,
      and distal levels.
AB  - The purpose of this study was to measure the internal and external anal
      sphincters using translabial ultrasound (TLU) at the proximal, mid, and distal
      levels of the anal sphincter complex. The human review committee approval was
      obtained and all women gave written informed consent. Sixty women presenting for
      gynecologic ultrasound for symptoms other than pelvic organ prolapse or urinary
      or anal incontinence underwent TLU. Thirty-six (60%) were asymptomatic and
      intact, 13 symptomatic and intact, and 11 disrupted. Anterior-posterior diameters
      of the internal anal sphincter at all levels and the external anal sphincter at
      the distal level were measured in four quadrants. Mean sphincter measurements are
      given for symptomatic and asymptomatic intact women and are comparable to
      previously reported endoanal MRI and ultrasound measurements.

PMID- 17221150
TI  - Breast duct anatomy in the human nipple: three-dimensional patterns and clinical
      implications.
AB  - BACKGROUND: The anatomy of the nipple has become clinically relevant. Diagnostic
      techniques access the breast through nipple ducts and surgeons offer nipple
      sparing mastectomy. There is variation in the number of ducts reported and little
      is known about the spatial location of ducts, their size, and their relationship
      to orifices on the surface. METHODS: Nipple specimens were taken from 129
      consecutive mastectomies. Each was sectioned coronally into 3 mm blocks and one
      section was prepared from each block. The number of ducts and cross-sectional
      areas of nipple and duct 'bundle' were recorded. Three nipples were sectioned at
      50 mum intervals and digitally reconstructed in three dimensions. RESULTS: The
      median number of ducts was 23 (interquartile range 19-28). Reconstructions and
      summary data from 25 nipples show a central duct bundle narrowing to form a
      'waist' as the ducts enter breast parenchyma. A three-dimensional reconstruction
      focusing on one nipple tip demonstrated 29 ducts arising from 15 orifices.
      Beneath the skin, most ducts are very narrow, gradually becoming larger deeper
      within the nipple. CONCLUSIONS: This work demonstrates that many ducts share a
      few common openings onto the surface of the nipple, explaining the observed
      discrepancy between number of ducts and of orifices. Neither duct diameter nor
      position predicts whether a duct system will terminate close to the nipple or
      pass deeper into the breast. These new insights into nipple anatomy will be of
      use in considering the reliability of a ductal approach to diagnosis and in
      planning nipple-sparing mastectomy.

PMID- 17221151
TI  - Predictive factors for late normal tissue complications following radiotherapy
      for breast cancer.
AB  - BACKGROUND AND PURPOSE: Radiotherapy after breast-conserving surgery is commonly
      applied to reduce recurrence of breast cancer but may cause acute and late side
      effects. To identify prognostic factors for the development of late toxicity
      after radiotherapy, we conducted a prospective study of breast cancer patients.
      PATIENTS AND METHODS: We assessed late complications of radiotherapy and
      collected information on epidemiologic factors in a cohort of breast cancer
      patients who had received radiotherapy after breast-conserving surgery. Among 416
      patients with complete follow-up data, the association between possible risk
      factors and development of late complications was evaluated using multivariate
      logistic regression analysis. RESULTS: After a median follow-up time of 51
      months, 131 (31.4%) patients presented with telangiectasia and 28 (6.7%) patients
      with fibrosis. We observed a strong association between development of
      telangiectasia and fibrosis (p < 0.01). Increasing age of the patient was a risk
      factor for both telangiectasia and fibrosis (p-value for trend <0.01 and 0.03,
      respectively). Patients with acute skin toxicity (odds ratio (OR) 1.8, 95%
      confidence interval (CI) 1.0-3.1) were at higher risk to develop telangiectasia.
      Long-term smoking was associated with a significant increase in risk of
      telangiectasia compared to non-smokers (OR 2.3, 95% CI 1.2-4.6). CONCLUSIONS: Our
      study revealed several factors other than radiation dose that may predispose to
      late complications following radiotherapy. Further understanding of differences
      in response to irradiation may advance individualized treatment and improve
      cosmetic outcome.

PMID- 17221152
TI  - Reduction in proliferation with six months of letrozole in women on hormone
      replacement therapy.
AB  - The objective of this study was to determine if 6 months of the aromatase
      inhibitor letrozole, administered to postmenopausal women taking a stable dose of
      hormone replacement remedy, would be safe and would modulate biomarkers of breast
      cancer risk. The intent was to reduce the proliferation marker Ki-67 while
      maintaining adequate systemic levels of estradiol so as to avoid perimenopausal
      symptoms. Postmenopausal women at high risk for development of breast cancer and
      taking a stable dose of estrogen or estrogen plus progestin were screened by
      random periareolar fine needle aspiration (RPFNA). To be eligible, the acquired
      breast epithelial cells had to be characterized as cytologic atypia or borderline
      atypia with > or =1,000 epithelial cells on the cytomorphology slide; plus > or
      =500 epithelial cells on a slide processed for Ki-67 immunocytochemistry. Forty
      two women were enrolled in the one arm study and received 2.5 mg letrozole per
      day for 6 months, followed by repeat assessment of biomarkers. Ki-67 was reduced
      by a median relative value of 66%. There was no significant change in breast cell
      cytomorphology; ER weighted index score; serum estradiol, testosterone, or IGF
      1:IGFBP-3 ratio; mammographic breast density, or frequency or severity of
      perimenopausal symptoms. Given the dramatic reduction in proliferation, the
      effect of letrozole on risk and response biomarkers should be explored further in
      a randomized, placebo-controlled Phase IIB breast cancer chemoprevention trial.

PMID- 17221153
TI  - Insulin receptor is an independent predictor of a favorable outcome in early
      stage breast cancer.
AB  - Fasting insulin is related to outcome in early breast cancer. We evaluated the
      expression of insulin receptor (IR) and its prognostic significance in patients
      with early stage breast cancer. Tumors from 191 patients with T1-3, N0-1, M0
      breast cancer who were enrolled at a single center of a multicenter cohort study
      were used to construct microarrays with subsequent immunohistochemical evaluation
      of IR, IGF-IR, ER, PgR and HER2/neu. Correlation of biomarker expression with
      traditional prognostic factors, serum biochemistry (notably insulin) and clinical
      outcome was assessed. IR was strongly positive (Allred score = 8) in 54% of
      tumors. High IR expression significantly correlated with favorable prognostic
      markers (low tumor grade, lymph node negativity and progesterone receptor
      positivity) but not with fasting levels of circulating insulin. At a median
      follow-up of 9.1 years, high vs. low IR expression (an Allred score of 8 vs. 0-7)
      was associated with statistically significant improved distant disease-free
      survival (multivariate hazard ratio (HR) = 0.4; P = 0.027) and overall survival
      (multivariate HR = 0.26; P = 0.005). IR is highly expressed in the majority of
      early stage breast cancers but this expression is not clearly down-regulated in
      the presence of high insulin levels. Furthermore, high expression of IR is
      independently and significantly associated with more favorable clinical outcomes.
      Follow-up intervention research is recommended.

PMID- 17221154
TI  - Changes in shoulder muscle size and activity following treatment for breast
      cancer.
AB  - BACKGROUND: Morbidity of the shoulder after breast cancer is a well-known
      phenomenon. MRI studies have shown muscle morbidity in cervical cancer and
      prostate cancer. In breast cancer clinical observations and patient reports
      include muscle morbidity in a number of muscles acting at the shoulder. Several
      of these muscles lie in the field of surgery and radiotherapy. Timed interaction
      between muscles that stabilise the shoulder and those acting as prime movers is
      essential to achieve a smooth scapulohumeral rthythm during functional elevation
      of the arm. METHOD: CROSS-SECTIONAL STUDY: Seventy-four women treated for
      unilateral carcinoma of the breast were included in the study. All patients
      filled out the Shoulder Pain and Disability Index (SPADI). EMG activity of four
      muscles was recorded during scaption on the affected and unaffected side. Muscle
      cross sectional area and signal intensity was determined from MRI scans. The
      association between EMG and covariates was determined using multiple linear
      regression techniques. RESULTS: Three of the 4 muscles on the affected side
      demonstrated significantly less EMG activity, particularly when lowering the arm.
      Upper trapezius demonstrated the greatest loss in activity. Decreased activity in
      both upper trapezius and rhomboid were significantly associated with an increase
      in SPADI score and increased time since surgery. Pectoralis major and minor were
      significantly smaller on the affected side. CONCLUSION: Muscles affected in the
      long term are the muscles associated with pain and disability yet are not in the
      direct field of surgery or radiotherapy. Primary muscle shortening and secondary
      loss of muscle activity may be producing a movement disorder similar to the
      'Dropped Shoulder Syndrome'. Exercise programmes should aim not only for range of
      movement but also for posture correction and education of potential long-term
      effects.

PMID- 17221155
TI  - Leukemia following breast cancer: an international population-based study of
      376,825 women.
AB  - PURPOSE: To quantify long-term temporal trends in the excess absolute risk (EAR)
      of secondary leukemia among breast cancer (BC) survivors, using multivariate
      analyses to evaluate the effects of subtype, age at BC diagnosis, attained age,
      and calendar year. PATIENTS AND METHODS: We identified 376,825 1-year survivors
      of BC within 4 nationwide, population-based cancer registries in Sweden, Denmark,
      Finland, and Norway (1943-2001). Estimates of EAR (per 100,000 person-years) were
      modeled using Poisson regression methods and cumulative risks calculated using a
      competing risk model. RESULTS: A total of 687 non-chronic lymphocytic leukemias
      (EAR = 9.05; 95% confidence interval (CI) = 7.5-10.7) was reported. Significantly
      elevated risks were observed for the first time for chronic myeloid leukemia
      (CML) (EAR = 2.06; 95% CI = 1.3-2.9) and acute lymphoblastic leukemia (ALL) (EAR
      = 0.62; 95% CI = 0.2-1.1), in addition to acute myeloid leukemia (AML) (EAR =
      5.00; 95% CI = 3.9-6.2). Excesses of CML, ALL, AML and all leukemias combined
      persisted over 25 years after BC diagnosis. For all leukemias, EAR decreased with
      increasing calendar year (P = 0.04) of BC diagnosis. Risk for all leukemia and
      AML by calendar year of BC diagnosis depended on age at diagnosis. For women
      diagnosed with BC after 1985, the 10-year cumulative risk of leukemia for those
      diagnosed before and after age 50 was small, 0.10% and 0.14%, respectively.
      CONCLUSIONS: Although secondary leukemia is a rare event, BC survivors experience
      statistically significant excesses for at least 25 years after diagnosis,
      including CML and ALL. Decreasing leukemia risks in recent calendar years likely
      reflect changes in treatment.

PMID- 17221156
TI  - BRCA1 genetic testing in 106 breast and ovarian cancer families from Southern
      Italy (Sicily): a mutation analyses.
AB  - PURPOSE: To evaluate the contribution of germline BRCA1 mutations in the
      incidence of hereditary and familial Breast Cancer (BC) and/or Ovarian Cancer
      (OC) in patients from Southern Italy (in the region of Sicily) and to identify a
      possible association between the higher frequency of BRCA1 mutations and a
      specific familial profile. EXPERIMENTAL DESIGN: A consecutive series of 650
      patients with BC and/or OC diagnosed between 1999 and 2005 were recruited from
      the Southern Italian region of Sicily, after interview at the "Regional Reference
      Centre for the Characterization and Genetic Screening of Hereditary Tumors" at
      the University of Palermo. Genetic counselling allowed us to recruit a total of
      106 unrelated families affected with breast and/or ovarian cancer screened for
      mutations occurring in the whole BRCA1 gene by automatic direct sequencing.
      RESULTS: Germline BRCA1 mutations were found in 17 of 106 (16%) Sicilian
      families. The HBOC profile had a major frequency (66%) of mutations (P < 0.01). A
      total of 28 sequence variants was identified. Seven of these were pathogenic, 5
      unknown biological variant (UV) and 16 polymorphisms. We also identified a
      pathological mutation (4843delC) as a possible Sicilian founder mutation.
      CONCLUSIONS: The present study is the first BRCA1 disease-associated mutations
      analysis in Southern Italian families. The early age of onset of such tumors and
      the association with the HBOC familial profile could be two valid screening
      factors for the identification of BRCA1 mutation carriers. Finally, we identified
      a BRCA1 mutation with a possible founder effect.

PMID- 17221157
TI  - Type of TP53 mutation and ERBB2 amplification affects survival in node-negative
      breast cancer.
AB  - Alterations of TP53 and ERBB2 have been shown to play important roles in the
      prognosis of breast cancer. The primary objective of this study is to
      characterize TP53 mutation types in node negative breast cancer and investigate
      their prognostic value, alone and in combination with ERBB2 amplification status.
      TP53 mutational status (exons 2-10) and ERBB2 amplification status were
      determined in tumor specimens from a prospective cohort of 543 women with node
      negative breast cancer. During a median follow-up of 120 months, there were 111
      disease recurrences, and 81 disease-related deaths (3 with cancer; 78 from
      cancer). Of 543 women, 133 (24.5%) carried mutations in exons 4-9 of the TP53
      gene. Seventy-one (53.4%) of these mutations were missense; whereas 62 (46.6%)
      were protein-truncating mutations. Women whose tumors had missense TP53 mutations
      were found to be at significantly higher risk of recurrence and death compared to
      those with wild type TP53, and they also tended to have worse prognosis compared
      to those with truncating mutations. Those with short truncated proteins tended to
      have good prognosis compared to those with long truncated proteins, but the risk
      of recurrence and death did not differ between those whose tumors exhibited
      conserved versus non-conserved mutations. Missense mutations, in combination with
      ERBB2 amplification, were observed in 4.6% of the tumors and dramatically
      affected the disease-specific survival (DSS) and disease-free survival (DFS) of
      the breast cancer patients. Our study suggests that the type of TP53 mutation,
      especially missense mutation, is a strong prognostic indicator for DFS and DSS in
      node-negative breast cancer, particularly in combination with ERBB2
      amplification.

PMID- 17221158
TI  - Mesenchymal stem cells as a vehicle for targeted delivery of CRAds to lung
      metastases of breast carcinoma.
AB  - PURPOSE: Alternative and complementary therapeutic strategies need to be
      developed for metastatic breast cancer. Virotherapy is a novel therapeutic
      approach for the treatment of cancer in which the replicating virus itself is the
      anticancer agent. However, the success of virotherapy has been limited due to
      inefficient virus delivery to the tumor site. The present study addresses the
      utility of human mesenchymal stem cells (hMSCs) as intermediate carriers for
      conditionally replicating adenoviruses (CRAds) to target metastatic breast cancer
      in vivo. EXPERIMENTAL DESIGN: HMSC were transduced with CRAds. We used a SCID
      mouse xenograft model to examine the effects of systemically injected CRAd loaded
      hMSC or CRAd alone on the growth of MDA-MB-231 derived pulmonary metastases
      (experimental metastases model) in vivo and on overall survival. RESULTS:
      Intravenous injection of CRAd loaded hMSCs into mice with established MDA-MB-231
      pulmonary metastatic disease homed to the tumor site and led to extended mouse
      survival compared to mice treated with CRAd alone. CONCLUSION: Injected hMSCs
      transduced with CRAds suppressed the growth of pulmonary metastases, presumably
      through viral amplification in the hMSCs. Thus, hMSCs may be an effective
      platform for the targeted delivery of CRAds to distant cancer sites such as
      metastatic breast cancer.

PMID- 17221159
TI  - Psychometric properties of the simplified Chinese version of the EORTC QLQ-BR53
      for measuring quality of life for breast cancer patients.
AB  - A Simplified Chinese version of the EORTC QLQ-BR53 was evaluated using responses
      from 233 patients with breast cancer in China by assessing the construct and
      criterion-related validity, internal consistency and test-retest reliability, and
      responsiveness as measured by score changes of the scales. Internal consistency
      reliability measured by Cronbach's coefficient alpha is greater than 0.75 for
      most multi-item scales except cognitive functioning (0.41) and breast symptoms
      (0.71). Test-retest reliability coefficients for all domains are greater than
      0.80 with the exception of physical functioning (0.65), social functioning
      (0.75), appetite loss (0.75), diarrhea (0.72), and body image (0.72). Correlation
      and factor analysis among domains and items showed good construct validity for
      both QLQ-C30 and QLQ-BR23. Score changes over time were observed in most domains
      except emotional functioning, global health status/QOL, dyspnoea, constipation,
      diarrhea, financial difficulties, sexual functioning, sexual enjoyment, and
      breast symptoms. Therefore, the Simplified Chinese version of QLQ-BR53 shows
      reasonable validity, reliability, and responsiveness and can be used to measure
      QOL for Chinese patients with breast cancer.

PMID- 17221160
TI  - Pathologic examination of sentinel lymph nodes in breast cancer by a single
      haematoxylin-eosin slide versus serial sectioning and immunocytokeratin staining:
      clinical implications.
AB  - BACKGROUND: The objective was to determine the additional value of pathologic
      examination using three-level sectioning and immunocytokeratin (ICK) staining of
      sentinel lymph node (SN) biopsies in cT1-2N0M0 breast carcinoma patients
      regarding lymph node staging and eligibility of systemic therapy taking primary
      tumor characteristics in account. METHODS: SN slides of 277 patients out of a
      total group of 961 patients known to have tumor-positive SNs detected by three
      level sectioning and ICK staining were re-examined. Haematoxylin-eosin (HE) slide
      level three was scanned for tumor deposits, and when present, extra capsular
      extension, maximum tumor diameter and number of positive SNs was noted. In
      addition, slides of the axillary dissection of non-SNs were reviewed, with
      determination of metastasis size and number of positive non-SNs. Primary tumor
      characteristics (grade, diameter, estrogen receptor) were recorded. RESULTS: In
      the single-HE examination, 26 cases SN micrometastasis and 6 macrometastasis were
      missed, 3 cases of micrometastasis were incorrectly classified as isolated tumor
      cells, and 9 patients with macrometastasis were misclassified as micrometastasis.
      In addition, in the tumor-negative single-HE examination, additional axillary
      lymph node dissection (ALND) revealed 6 cases of non-SN metastasis. Taking
      primary tumor factors into account for adjuvant systemic therapy, 21 patients
      would have been denied the choice for systemic therapy if single-HE examination
      was carried out only. CONCLUSIONS: Single-HE examination of SN may result in a
      reduction of locoregional and systemic treatment according to treatment
      guidelines then current in the Netherlands.

PMID- 17221161
TI  - Enzymes and proteins from extremophiles as hyperstable probes in nanotechnology:
      the use of D-trehalose/D-maltose-binding protein from the hyperthermophilic
      archaeon Thermococcus litoralis for sugars monitoring.
AB  - The D-trehalose/D-maltose-binding protein (TMBP), a monomeric protein of 48 kDa,
      is one component of the trehalose and maltose (Mal) uptake system. In the
      hyperthermophilic archaeon Thermococcus litoralis, this is mediated by a protein
      dependent ATP-binding cassette system transporter. The gene coding for a
      thermostable TMBP from the archaeon T. litoralis has been cloned, and the
      recombinant protein has been expressed in E. coli. The recombinant TMBP has been
      purified to homogeneity and characterized. It exhibits the same functional and
      structural properties as the native one. In fact, it is highly thermostable and
      binds sugars, such as maltose, trehalose and glucose, with high affinity. In this
      work, we have immobilized TMBP on a porous silicon wafer. The immobilization of
      TMBP to the chip was monitored by reflectivity and Fourier Transformed Infrared
      spectroscopy. Furthermore, we have tested the optical response of the protein
      Chip complex to glucose binding. The obtained data suggest the use of this
      protein for the design of advanced optical non-consuming analyte biosensors for
      glucose detection.

PMID- 17221162
TI  - Continuous enrichment culturing of thermophiles under sulfate and nitrate
      reducing conditions and at deep-sea hydrostatic pressures.
AB  - A continuous culture bioreactor was developed to enrich for nitrate and sulfate
      reducing thermophiles under in situ deep-sea pressures. The ultimate objective of
      this experimental design was to be able to study microbial activities at chemical
      and physical conditions relevant to seafloor hydrothermal vents. Sulfide, sulfate
      and oxide minerals from sampled seafloor vent-chimney structures [East Pacific
      Rise (9 degrees 46'N)] served as source mineral and microbial inoculum for
      enrichment culturing using nitrate and sulfate-enriched media at 70 and 90
      degrees C and 250 bars. Changes in microbial diversity during the continuous
      reaction flow were monitored using denaturing gradient gel electrophoresis (DGGE)
      of PCR amplified 16S rRNA gene fragments. Time series changes in fluid chemistry
      were also monitored throughout the experiment to assess the feedback between
      mineral-fluid reaction and metabolic processes. Data indicate a shift from the
      dominance of epsilon Proteobacteria in the initial inoculum to the several
      Aquificales-like phylotypes in nitrate-reducing enrichment media and
      Thermodesulfobacteriales in the sulfate-reducing enrichment media. Methanogens
      were detected in the original sulfide sample and grew in selected sulfate
      enriched experiments. Microbial interactions with anhydrite and pyrrhotite in the
      chimney material resulted in measurable changes in fluid chemistry despite a
      fluid residence time only 75 min in the reactor. Changes in temperature rather
      than source material resulted in greater differences in microbial enrichments and
      mediated geochemical reactions.

PMID- 17221163
TI  - Cyclic AMP: swing that message!

PMID- 17221164
TI  - Two axes in platelet-derived growth factor signaling: tyrosine phosphorylation
      and reactive oxygen species.
AB  - The tyrosine phosphorylation cascade is a hallmark of platelet-derived growth
      factor (PDGF)- induced signal transduction. The amplitude and propagation of the
      tyrosine phosphorylation signal relies on the balance between tyrosine kinase and
      tyrosine phosphatase. The tyrosine kinase is latent in the absence of
      stimulation, whereas the tyrosine phosphatase is highly and constitutively
      active. Therefore, the kinase activation should be accompanied by temporal and
      spatial inactivation of tyrosine phosphatase to achieve the robust amplification
      of tyrosine phosphorylation. For the past decade, reactive oxygen species have
      been receiving a great deal of attention with regard to their ability to shut
      down tyrosine phosphatase activities in a reversible manner. In this article, the
      crosstalk between tyrosine phosphorylation and reactive oxygen species in PDGF
      signaling is discussed.

PMID- 17221165
TI  - Heat shock protein 60: regulatory role on innate immune cells.
AB  - Human heat shock protein 60 (Hsp60) exhibits immunoregulatory properties,
      primarily by inducing pro-inflammatory responses in innate immune cells.
      Extensive analyses identified specific receptor structures for the interaction of
      Hsp60 with these cells. The existence of distinct receptor structures responsible
      for Hsp60 binding and for Hsp60-induced release of pro-inflammatory mediators has
      been demonstrated, implying that the interaction of Hsp60 with innate immune
      cells is a multifaceted process. Distinct Hsp60 epitopes responsible for binding
      to innate immune cells and for the activation of these cells have been
      identified. Depending on the cell-type, the amino acid (aa) region 481-500 or the
      regions aa241-260, aa391-410 and aa461-480 are involved in Hsp60-binding to
      innate immune cells. An entirely different Hsp60-region, aa354-365 was found to
      bind lipopolysaccharide, thereby mediating the pro-inflammatory effects of Hsp60.
      Because of its immunoregulatory properties, Hsp60 has been proposed to act as
      intercellular danger signal, controlling innate and adaptive immune reactions.

PMID- 17221166
TI  - Enzymatic hydroxylation of aromatic compounds.
AB  - Selective hydroxylation of aromatic compounds is among the most challenging
      chemical reactions in synthetic chemistry and has gained steadily increasing
      attention during recent years, particularly because of the use of hydroxylated
      aromatics as precursors for pharmaceuticals. Biocatalytic oxygen transfer by
      isolated enzymes or whole microbial cells is an elegant and efficient way to
      achieve selective hydroxylation. This review gives an overview of the different
      enzymes and mechanisms used to introduce oxygen atoms into aromatic molecules
      using either dioxygen (O(2)) or hydrogen peroxide (H(2)O(2)) as oxygen donors or
      indirect pathways via free radical intermediates. In this context, the article
      deals with Rieske-type and alpha-keto acid-dependent dioxygenases, as well as
      different non-heme monooxygenases (di-iron, pterin, and flavin enzymes),
      tyrosinase, laccase, and hydroxyl radical generating systems. The main emphasis
      is on the heme-containing enzymes, cytochrome P450 monooxygenases and
      peroxidases, including novel extracellular heme-thiolate haloperoxidases
      (peroxygenases), which are functional hybrids of both types of heme-biocatalysts.

PMID- 17221167
TI  - Action and interactions at microtubule ends.
AB  - Microtubule dynamic instability is fundamentally important to the way cells
      respond to their environment and segregate their genetic material. A disparate
      class of proteins defined by their localisation to growing microtubule plus ends
      ('+TIPS') play a key role in controlling microtubule dynamics and organisation.
      They directly impact upon the behaviour of the microtubule tip and link this
      structure to interfaces that include kinetochores and the cortex of the cell.
      Surprisingly, some +TIPs also have important functions at the microtubule minus
      end. These properties contribute to the important roles played by +TIPs in
      processes such as mitosis and cell migration. This review examines how recent
      advances have impacted our understanding of +TIP function in mammalian cells,
      with emphasis on the emergence of the EB1 family as a core component of +TIP
      activities. An overview of the use of +TIP imaging as a tool for the cell
      biologist is also presented.

PMID- 17221168
TI  - Interferon-gamma inhibits collagen phagocytosis in human fibroblasts by inducing
      subcortical actin assembly and reducing ability of beta1 integrin to bind to
      collagen.
AB  - OBJECTIVE: We investigated the possible roles of interferon-gamma (IFN-gamma) in
      modulation of extracellular and intracellular routes of collagen digestion by
      human fibroblasts. METHODS: Human gingival fibroblasts were treated with IFN
      gamma, after which matrix metalloproteinase-1 (MMP-1) activation was determined.
      Following the IFN-gamma treatment, cells were further incubated with either
      activating antibody for beta1 integrin or actin monomer-sequestering agent
      latrunculin B before incubation with collagen-coated fluorescent beads.
      Thereafter, the binding and internalization of the beads were assessed. RESULTS:
      IFN-gamma had no significant effect on MMP-1 activation, however, it reduced the
      binding of collagen-coated beads in the minimum affinity range and, subsequently,
      internalization of the beads. The inhibitory effects of IFN-gamma were partially
      reversed by adding either the beta1 integrin activating antibody or latrunculin
      B. CONCLUSIONS: Although IFN-gamma does not appreciably moderate the
      extracellular route of collagen digestion by human fibroblasts, the reduced level
      of collagen phagocytosis by IFN-gamma in the cells may contribute to fibrosis in
      inflamed connective tissues. Further, IFN-gamma may decrease the binding of
      collagen and following phagocytosis in cells by inducing a subcortical actin
      assembly and reducing the ability of beta1 integrin to bind to collagen.

PMID- 17221169
TI  - Adjunctive low-dose doxycycline therapy effect on clinical parameters and
      gingival crevicular fluid tissue plasminogen activator levels in chronic
      periodontitis.
AB  - OBJECTIVE AND DESIGN: The present study examined effectiveness of low-dose
      doxycycline (LDD) in combination with nonsurgical therapy on gingival crevicular
      fluid (GCF) tissue plasminogen activator (t-PA) levels and clinical parameters in
      chronic periodontitis (CP) a over 12-month period. METHODS: GCF samples were
      collected, probing depth (PD), clinical attachment level (CAL), gingival index
      (GI) and plaque index were recorded at baseline, 3, 6, 9 and 12 months. CP
      patients (n = 65) were randomized to LDD or placebo groups. LDD group received
      LDD (20 mg) b.i.d for 3-months plus and root planing (SRP), while placebo group
      was given placebo capsules b.i.d for 3-months plus SRP. GCF t-PA levels were
      determined by ELISA. Friedman, Wilcoxon and Mann-Whitney test was used for
      statistical analysis. RESULTS: Significant improvement was observed in all
      clinical parameters in both groups over 12-month period (p < 0.01). LDD group had
      lower PD, CAL and GI scores than placebo group at 6, 9 and 12-months (p < 0.05).
      GCF t-PA levels reduced in both groups over 12-month period (p < 0.01). LDD group
      had lower GCF t-PA levels than placebo group at 6 and 9-months (p < 0.05).
      CONCLUSIONS: These results provide additional information about usefulness of LDD
      therapy as an adjunct to nonsurgical therapy in long-term management of
      periodontitis.

PMID- 17221170
TI  - Pro- and anti-inflammatory activities of the latex from Calotropis procera (Ait.)
      R.Br. are triggered by compounds fractionated by dialysis.
AB  - OBJECTIVES AND DESIGN: Previous studies have described pro- and anti-inflammatory
      activities displayed by the latex from Calotropis procera. This report aims to
      clarify these observations and shows that such activities can be segregated from
      the whole latex. METHODS: The latex was divided into water-soluble fractions
      devoid of poly-isoprene by centrifugation and dialysis and both the activities
      were assayed by the peritonitis model in rats. The drugs dexamethasone,
      thalidomide, meclizine, indomethacin and celecoxib were used to modulate the
      inflammatory stimuli. RESULTS: Inflammation in rats was observed 2 h after
      intraperitoneal administration of the stimulus (DL fraction) in a dose dependent
      manner. This activity was inhibited by previous intravenous injection of
      dexamethasone, thalidomide and meclizine. Indomethacin and celecoxib did not
      reverse inflammation. These results suggest the involvement of histamine release
      and TNF-alpha mediated inflammation while prostaglandins seem not to be required.
      The anti-inflammatory fraction (NDL) inhibited inflammation triggered by
      proinflammatory fraction (DL) suggesting that NDL ought to follow a similar
      pathway of action to that of the anti-inflammatory drugs that were able to
      inhibit inflammation triggered by DL. CONCLUSIONS: Pro- and anti-inflammatory
      activities of the latex are displayed by compounds suitable to be fractionated on
      the basis of their molecular size.

PMID- 17221171
TI  - Zymosan priming protects rats against pulmonary oxygen toxicity.
AB  - OBJECTIVE: To determine whether zymosan priming protects rats against oxygen
      toxicity. METHODS: 37 rats were used with 6 treatment groups. 11 received zymosan
      priming (3 daily i. v. injections with 15 mg zymosan and 2 days rest) before 52 h
      exposure to either normobaric hyperoxia (ZP group, 5 rats) or air (ZPA group, 6
      rats)]. Two other groups received saline (Saline group, 9 rats) or zymosan by i.
      p. injection (Zip group, 6 rats) before hyperoxia. A fifth group received a non
      priming (NP) treatment with zymosan before hyperoxia (ZNP group, 6 rats, single
      i. v. injection) and a final group received no treatment (Air group, 5 rats).
      Pleural effusions and lung injury were then assessed. RESULTS: Saline, Zip or ZNP
      rats developed massive, proteinaceous pleural effusions indicative of oxygen
      toxicity while ZP rats did not (0.02 +/- 0.01 ml). The ratios of effusion protein
      to plasma protein concentration and wet/dry lung weight were also significantly
      reduced in ZP rats following hyperoxia. CONCLUSIONS: Zymosan priming protects
      rats against pulmonary oxygen toxicity.

PMID- 17221172
TI  - Presence of D8/17 B-cell marker in patients with poststreptococcal reactive
      arthritis.
AB  - An elevated expression of the alloantigen D8/17 on B lymphocytes has been
      previously proposed as a susceptibility marker in rheumatic fever. The aim of the
      study was to investigate the presence of the D8/17 marker on B lymphocytes in
      poststreptococcal reactive arthritis (PSRA). The study sample included 19
      patients (15 boys, 4 girls; mean age 11.7 +/- 5.4 years) who were diagnosed with
      PSRA (mean age at diagnosis, 9.4 +/- 5.6 years) and 18 healthy controls (10 boys
      and 8 girls) matched for ethnic background. B-cell D8/17 expression was tested by
      flow cytometry assay using monoclonal antibodies. Laboratory results showed a
      higher expression of D8/17 in the patient group (23.1 +/- 10.4%, range 11.6
      51.9%) than in the control group (17.1 +/- 8.2%, range 7.1-35.7) in controls;
      this difference was statistically significant after log transformation of the
      data (P = 0.035). The high rate of expression of the D8/17 marker in patients
      with PSRA suggests that RF and PSRA share the same genetic susceptibility.

PMID- 17221174
TI  - Factors affecting sagittal malalignment due to cage subsidence in standalone cage
      assisted anterior cervical fusion.
AB  - Fusion of cervical spine in kyphotic alignment has been proven to produce an
      acceleration of degenerative changes at adjacent levels. Stand-alone cages are
      reported to have a relatively high incidence of implant subsidence with secondary
      kyphotic deformity. This malalignment may theoretically lead to adjacent segment
      disease in the long term. The prospective study analysed possible risk factors
      leading to cage subsidence with resulting sagittal malalignment of cervical
      spine. Radiographic data of 100 consecutive patients with compressive radiculo
      /myelopathy due to degenerative disc prolapse or osteophyte formation were
      prospectively collected in those who were treated by anterior cervical discectomy
      and implantation of single type interbody fusion cage. One hundred and forty four
      implants were inserted altogether at one or two levels as stand-alone cervical
      spacers without any bone graft or graft substitute. All patients underwent
      standard anterior cervical discectomy and the interbody implants were placed
      under fluoroscopy guidance. Plain radiographs were obtained on postoperative days
      one and three to verify position of the implant. Clinical and radiographic follow
      up data were obtained at 6 weeks, 3 and 6 months and than annually in outpatient
      clinic. Radiographs were evaluated with respect to existing subsidence of
      implants. Subsidence was defined as more than 2 mm reduction in segmental height
      due to implant migration into the adjacent end-plates. Groups of subsided and non
      subsided implants were statistically compared with respect to spacer distance to
      the anterior rim of vertebral body, spacer versus end-plate surface ratio, amount
      of bone removed from adjacent vertebral bodies during decompression and pre-
      versus immediate postoperative intervertebral space height ratio. There were 18
      (18%) patients with 19 (13.2%) subsided cages in total. No patients experienced
      any symptoms. At 2 years, there was no radiographic evidence of accelerated
      adjacent segment degeneration. All cases of subsidence occurred at the anterior
      portion of the implant: 17 cases into the inferior vertebra, 1 into the superior
      and 1 into both vertebral bodies. In most cases, the process of implant settling
      started during the perioperative period and its progression did not exceed three
      postoperative months. There was an 8.7 degrees average loss of segmental lordosis
      (measured by Cobb angle). Average distance of subsided intervertebral implants
      from anterior vertebral rim was found to be 2.59 mm, while that of non-subsided
      was only 0.82 mm (P < 0.001). Spacer versus end-plate surface ratio was
      significantly smaller in subsided implants (P < 0.001). Ratio of pre- and
      immediate postoperative height of the intervertebral space did not show
      significant difference between the two groups (i.e. subsided cages were not in
      overdistracted segments). Similarly, comparison of pre- and postoperative amount
      of bone mass in both adjacent vertebral bodies did not show a significant
      difference. Appropriate implant selection and placement appear to be the key
      factors influencing cage subsidence and secondary kyphotisation of box-shaped,
      stand-alone cages in anterior cervical discectomy and fusion. Mechanical support
      of the implant by cortical bone of the anterior osteophyte and maximal cage to
      end-plate surface ratio seem to be crucial in the prevention of postoperative
      loss of lordosis. Our results were not able to reflect the importance of end
      plate integrity maintenance; the authors would, however, caution against
      mechanical end-plate damage. Intraoperative overdistraction was not shown to be a
      significant risk factor in this study. The significance of implant subsidence in
      acceleration of degenerative changes in adjacent segments remains to be evaluated
      during a longer follow-up.

PMID- 17221175
TI  - [Techniques for wrist arthroscopy].

PMID- 17221173
TI  - Beneficial effect of treatment with cyclosporin A in a case of refractory
      antisynthetase syndrome.
AB  - We report a case of idiopathic inflammatory myopathy accompanied with the
      presence of anti-Jo1 antibodies and complicated by diffuse parenchymal lung
      disease (antisynthetase syndrome). Efficacy of different therapeutic agents,
      including corticosteroids, cyclophosphamide and cyclosporin A, is described. We
      present beneficial effect of cyclosporin A and corticosteroids regimen, and
      confirm no benefits of plasmapheresis. An interesting association of the disease
      onset with toxoplasmosis infection is discussed and difficulties regarding
      diagnosis of cardiac involvement are addressed. We also review other case reports
      of this rare disorder of poor prognosis.

PMID- 17221176
TI  - [Subdental synchondrosis. Computed tomographic and histologic investigation on
      morphological aspects of fracture at the base of the dens in 36 human axis
      specimens].
AB  - BACKGROUND: During development of the axis, four different ossification centers
      are formed. The two cranial ossification centers are demarcated from the
      ossification center of the vertebral corpus by a subdental synchondrosis. During
      further development the subdental synchondrosis--which is thought to close
      spontaneously--might not close completely, which leads to the necessity for
      differentiating synchondrotic remnants from a fracture at the base of the dens
      (type II according to Anderson and D'Alonzo). RESULTS: To characterize the
      architecture of the axis with particular attention to the subdental
      synchondrosis, the axis was harvested from 36 age- and gender-matched patients
      covering the human aging process from adolescence to senescence. In all specimens
      bone mineral density (BMD) was measured by peripheral quantitative computed
      tomography (pQCT). Morphological analysis after undecalcified processing of all
      specimens revealed a persistency of the subdental synchondrosis in 87% of all
      patients. Histological characterization of the subdental synchondrosis showed a
      cartilaginous structure interspersed with focal mineralization. Furthermore,
      static histomorphometric analysis revealed that trabecular bone volume and
      cortical thickness were significantly reduced within the base of the axis as
      compared to the dens and the corpus, respectively. CONCLUSION: Taken together,
      these results provide evidence that the base of the axis is a structurally
      distinct region. Besides well-recognized biomechanical aspects, these results
      suggest that the structure of the base of the axis might contribute to the
      occurrence of fractures of the axis and offer an additional explanation for the
      observation of nonunion after type II dens fractures.

PMID- 17221177
TI  - Pricing matrix model: dealing with uncertainty.
AB  - A previous publication in this journal showed that the pricing matrix model (PMM)
      allows an assessment of the pricing potential of a new innovative product. When
      the PMM is going to be used for the determination of a drug price for a new drug
      in the strategic product planning process, it is important that this methodology
      is reliable. In the initial paper the PMM only yielded an expected price for the
      new antidepressant without generating an estimate of the probability that the new
      drug would indeed be listed at this expected price. In this manuscript we present
      various methodologies to deal with uncertainty in the PMM. We introduce the
      concept of price acceptability curves. The conclusion of this paper is that the
      incorporation of uncertainty into the PMM will lead to a more accurate assessment
      of the pricing potential of a new drug.

PMID- 17221179
TI  - Vaccination versus "wait and treat": how to subsidize them?
AB  - In this paper we discuss the application of different co-payment rates to
      alternative medical strategies. Two such strategies are considered: a
      "vaccination strategy", in which patients apply preventive measures before
      knowing if they have the disease, and a "wait and treat" strategy, in which
      patients are treated later only if they contract the disease. We show the second
      approach should be more generously subsidized by the regulator. This is, at least
      at first sight, a surprising result.

PMID- 17221178
TI  - The impact of home hospitalization on healthcare costs of exacerbations in COPD
      patients.
AB  - Home-hospitalization (HH) improves clinical outcomes in selected patients with
      chronic obstructive pulmonary disease (COPD) admitted at the emergency room due
      to an exacerbation, but its effects on healthcare costs are poorly known. The
      current analysis examines the impact of HH on direct healthcare costs, compared
      to conventional hospitalizations (CH). A randomized controlled trial was
      performed in two tertiary hospitals in Barcelona (Spain). A total of 180
      exacerbated COPD patients (HH 103 and CH 77) admitted at the emergency room were
      studied. In the HH group, a specialized respiratory nurse delivered integrated
      care at home. The average direct cost per patient was significantly lower for HH
      than for CH, with a difference of euro 810 (95% CI, euro 418-1,169) in the mean
      cost per patient. The magnitude of monetary savings attributed to HH increased
      with the severity of the patients considered eligible for the intervention.

PMID- 17221180
TI  - Economic impact of shifting the locus of care for neuropathic pain from
      specialists to general practitioners.
AB  - We developed a decision-analytic model to examine the economic impact of shifting
      the locus of care for patients with painful neuropathies from specialists to GPs.
      The impetus for such a shift was assumed to be a formal education program,
      focusing on the recognition and treatment of neuropathic pain, conducted for GPs.
      In the model, all patients with neuropathic pain were assumed to initiate care
      with their GPs and then be referred to specialists and, ultimately, pain clinics
      as required for adequate pain control. Two alternative scenarios were examined-
      the "current" arrangement in which most patients were assumed to be referred for
      treatment by specialists and pain clinics and a "hypothetical" arrangement in
      which GPs were assumed to play an expanded role in the treatment of neuropathic
      pain and which, therefore, often precluded the need for referral. The model was
      populated with clinical, epidemiologic, and economic data from Norway. A total of
      34,951 persons in Norway were estimated to seek care for painful neuropathies
      each year. The formal education program was assumed to cost 1.5 million Kroner
      (NOK). Shifting the locus of care from specialists to GPs would result in 4,715
      additional GP visits, but 12,123 fewer specialist visits and 7,967 fewer visits
      to pain clinics. This change would result in estimated savings to the Norwegian
      health-care system in 2004 of 74.1 million NOK (approx. US $11.9 million). A
      partial shift in the locus of care of painful neuropathies from specialists to
      GPs may result in substantial cost savings to the Norwegian health-care system.

PMID- 17221181
TI  - Influence of bacterial resistances on the efficiency of antibiotic treatments for
      community-acquired pneumonia.
AB  - The objective of this paper is to perform a cost-effectiveness analysis of the
      oral antibiotics used in Spain for the ambulatory treatment of community-acquired
      pneumonia. Our analysis takes into account the influence of bacterial resistances
      on the cost-effectiveness ratio of antibiotic alternatives from the viewpoint of
      the public insurer. A deterministic decision analysis model is used to simulate
      the impact of treatment alternatives on both patients' health and resource
      consumption. Amoxicillin 1 g may be the most efficient therapy for treating
      typical pneumonia, as long as the physician is able to discriminate clinically
      the aetiology of the process with a high degree of reliability. However, for
      those pathological pictures in which the aetiology cannot be discriminated
      clinically, and for those in which the consequences of incorrect diagnosis are
      serious according to clinical criteria, moxifloxacin is the most effective and
      efficient option.

PMID- 17221182
TI  - The burden of type 2 diabetes in Serbia and the cost-effectiveness of its
      management.
AB  - The purpose of this study was to analyse whether the nationwide application of
      the national Serbian guideline for diabetes mellitus (NSGDM) would save a
      relevant amount of disability-adjusted life years (DALYs) and/or reduce the
      medical cost of treating diabetic patients in Serbia, as compared to the present
      situation. Disability-adjusted life years were calculated for Serbia and the cost
      effectiveness was analysed in eight population groups under ideal and present
      conditions; prevalent and incident cases were each split up for patients with
      blood glucose that was well controlled and that was uncontrolled. Under ideal
      conditions, i.e., according to the NSGDM, 8,031 DALYs could be saved with a
      potential cost reduction at the same time of approximately 19 million Euros. The
      implementation of the NSGDM in clinical practice bears a great potential to save
      lives and reduce years lived with lowered quality of life, but in addition it may
      reduce costs by about a quarter.

PMID- 17221183
TI  - Is it possible to predict renal function in small animals using a multi-pinhole
      SPECT system?

PMID- 17221184
TI  - Synthesis and in vivo evaluation of a novel 5-HT1A receptor agonist radioligand
      [O-methyl- 11C]2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4
      triazine-3,5(2H,4H)dione in nonhuman primates.
AB  - PURPOSE: Serotonin1A (5-HT1A) receptors exist in high- and low-affinity states,
      and agonist ligands bind preferentially to the high-affinity state of the
      receptor and provide a measure of functional 5-HT1A receptors. Although the
      antagonist tracers are established PET ligands in clinical studies, a successful
      5-HT1A receptor agonist radiotracer in living brain has not been reported.
      [11C]MPT, our first-generation agonist radiotracer, shows in vivo specificity in
      baboons; however, its utility is limited owing to slow washout and immeasurable
      plasma free fraction. Hence we performed structure-activity relationship studies
      of MPT to optimize a radiotracer that will permit valid quantification of 5-HT1A
      receptor binding. We now report the synthesis and evaluation of [11C]MMP as an
      agonist PET tracer for 5-HT1A receptors in baboons. METHODS: In vitro binding
      assays were performed in bovine hippocampal membranes and membranes of CHO cells
      expressing 5-HT1A receptors. [11C] labeling of MMP was performed by reacting
      desmethyl-MMP with [11C]CH(3)OTf. In vivo studies were performed in baboons, and
      blocking studies were conducted by pretreatment with 5-HT1A receptor ligands WAY
      100635 and (+/-)-8-OH-DPAT. RESULTS: MMP is a selective 5-HT1A receptor agonist
      (Ki 0.15 nM). Radiosynthesis of [11C]MMP was achieved in 30 +/- 5% (n = 15) yield
      at EOS with a specific activity of 2,600 +/- 500 Ci/mmol (n = 12). PET studies in
      baboons demonstrated specific binding of [11C]MMP to 5-HT1A receptor-enriched
      brain regions, as confirmed by blockade with WAY-100635 and (+/-)-8-OH-DPAT.
      CONCLUSION: We identified [11C]MMP as an optimal agonist PET tracer that shows
      quantifiable, specific binding in vivo to 5-HT1A receptors in baboons.

PMID- 17221185
TI  - Sulcus vocalis: a review.
AB  - Sulcus vocalis is described as a groove at the free edge of the vocal fold.
      Different types have been described: sulcus type I is superficial and may be
      considered as moreless physiologic. Sulcus type IIa corresponds to a kind of
      vergeture along the margin of the vocal fold. Its deepness is variable but sulcus
      vergeture may involve deeper layers of the lamina propria. Sulcus type IIb or
      pounch may be considered as an open cyst. Sulcus lead to a complex glottic
      dysfunction with, in the same time, a glottal leakage responsible for the breathy
      component of the dysphonia and a stiffness of the free edge responsible for the
      roughness. Diagnosis may be difficult even with the help of stroboscopy and
      finally is sometimes done only under general anesthesia. Etiology remains
      controversial and the authors present arguments for each theory, acquired or
      congenital. Treatment options include phonosurgery and speech therapy but
      phonosurgery gives results often disappointing and surgical treatment must be
      indicated prudently and patient must be intensively informed on what he or she
      can expect from the treatment that is mainly an increase of the loudness of the
      voice.

PMID- 17221186
TI  - Midkine as a prognostic marker for gastrointestinal stromal tumors.
AB  - PURPOSE: Midkine (MK), a heparin-binding growth factor, has an important role in
      cancer progression. The outcome of patients with gastrointestinal stromal tumors
      (GISTs) is correlated with tumor size and mitotic count. The aim of this study
      was to determine MK expression in GISTs. METHODS: Midkine was detected in 31
      (55%) of 57 surgically resected GISTs by immunohistochemistry with a rabbit
      antibody against MK and peroxidase method. RESULTS: A significant worse outcome
      of MK-positive patients was found (P < 0.05; log rank test). Multivariate Cox
      regression analysis showed an independent prognostic impact (relative risk for
      overall survival 3.64; P < 0.05). Interestingly, MK expression was significantly
      associated with mitotic rate (P < 0.05; Chi-squared test), but not with tumor
      size (P = 0.97). CONCLUSIONS: Taken together, MK is a prognostic marker for GIST
      patients. MK might also be a useful peripheral tumor marker since it can be
      detected in peripheral serum. Future studies should involve higher GIST patient
      numbers including tumor and serum samples for detection of MK.

PMID- 17221188
TI  - The search for "objective" criteria of ARDS.

PMID- 17221187
TI  - Year in review in Intensive Care Medicine, 2006. II. Infections and sepsis,
      haemodynamics, elderly, invasive and noninvasive mechanical ventilation, weaning,
      ARDS.

PMID- 17221190
TI  - Anaerobic glycerol production by Saccharomyces cerevisiae strains under
      hyperosmotic stress.
AB  - Glycerol formation is vital for reoxidation of nicotinamide adenine dinucleotide
      (reduced form; NADH) under anaerobic conditions and for the hyperosmotic stress
      response in the yeast Saccharomyces cerevisiae. However, relatively few studies
      have been made on hyperosmotic stress under anaerobic conditions. To study the
      combined effect of salt stress and anaerobic conditions, industrial and
      laboratory strains of S. cerevisiae were grown anaerobically on glucose in batch
      cultures containing 40 g/l NaCl. The time needed for complete glucose conversion
      increased considerably, and the specific growth rates decreased by 80-90% when
      the cells were subjected to the hyperosmotic conditions. This was accompanied by
      an increased yield of glycerol and other by-products and reduced biomass yield in
      all strains. The slowest fermenting strain doubled its glycerol yield (from 0.072
      to 0.148 g/g glucose) and a nearly fivefold increase in acetate formation was
      seen. In more tolerant strains, a lower increase was seen in the glycerol and in
      the acetate, succinate and pyruvate yields. Additionally, the NADH-producing
      pathway from acetaldehyde to acetate was analysed by overexpressing the stress
      induced gene ALD3. However, this had no or very marginal effect on the acetate
      and glycerol yields. In the control experiments, the production of NADH from
      known sources well matched the glycerol formation. This was not the case for the
      salt stress experiments in which the production of NADH from known sources was
      insufficient to explain the formed glycerol.

PMID- 17221191
TI  - Effect of dilution rate on the microbial structure of a mesophilic butyrate
      degrading methanogenic community during continuous cultivation.
AB  - We constructed two mesophilic anaerobic chemostats that were continuously fed
      with synthetic wastewater containing butyrate as the sole source of carbon and
      energy. Steady-state conditions were achieved at dilution rates between 0.025 and
      0.7 day(-1). Butyrate, fed into the chemostat, was almost completely mineralized
      to CH(4) and CO(2) at dilution rates below 0.5 day(-1). The butyrate-degrading
      methanogenic communities in the chemostats at dilution rates between 0.025 and
      0.7 day(-1) were monitored based on the 16S rRNA gene, using molecular biological
      techniques including clone library analysis, denaturing gradient gel
      electrophoresis, and quantitative real-time polymerase chain reaction. The
      aceticlastic methanogen Methanosaeta and the hydrogenotrophic methanogen
      Methanoculleus dominated in methanogens at low dilution rates, whereas the
      aceticlastic methanogen Methanosaeta, Methanosarcina, the hydrogenotrophic
      methanogen Methanoculleus, and Methanospirillum dominated at high dilution rates.
      Bacteria affiliated with the family Syntrophaceae in the phylum Proteobacteria
      predominated at the low dilution rate of 0.025 day(-1), whereas bacteria
      affiliated with the phylum Firmicutes and Candidate division OP3 predominated at
      high dilution rates. A significant quantity of bacteria closely related to the
      genus Syntrophomonas was detected at high dilution rates. Dilution rate showed an
      apparent effect on archaeal and bacterial communities in the butyrate-fed
      chemostats.

PMID- 17221189
TI  - Assessing pulmonary permeability by transpulmonary thermodilution allows
      differentiation of hydrostatic pulmonary edema from ALI/ARDS.
AB  - OBJECTIVE: To test whether assessing pulmonary permeability by transpulmonary
      thermodilution enables to differentiate increased permeability pulmonary edema
      (ALI/ARDS) from hydrostatic pulmonary edema. DESIGN: Retrospective review of
      cases. SETTING: A 24-bed medical intensive care unit of a university hospital.
      PATIENTS: Forty-eight critically ill patients ventilated for acute respiratory
      failure with bilateral infiltrates on chest radiograph, a PaO(2)/FiO(2) ratio <
      300 mmHg and extravascular lung water indexed for body weight >/= 12 ml/kg.
      INTERVENTION: We assessed pulmonary permeability by two indexes obtained from
      transpulmonary thermodilution: extravascular lung water/pulmonary blood volume
      (PVPI) and the ratio of extravascular lung water index over global end-diastolic
      volume index. The cause of pulmonary edema was determined a posteriori by three
      experts, taking into account medical history, clinical features,
      echocardiographic left ventricular function, chest radiography findings, B-type
      natriuretic peptide serum concentration and the time-course of these findings
      with therapy. Experts were blind for pulmonary permeability indexes and for
      global end-diastolic volume. MEASUREMENTS AND RESULTS: ALI/ARDS was diagnosed in
      36 cases. The PVPI was 4.7+/-1.8 and 2.1+/-0.5 in patients with ALI/ARDS and
      hydrostatic pulmonary edema, respectively (p<0.05). The extravascular lung water
      index/global end-diastolic volume index ratio was 3.0 x 10(-2)+/-1.2 x 10(-2) and
      1.4 x 10(-2)+/-0.4 x 10(-2) in patients with ALI/ARDS and with hydrostatic
      pulmonary edema, respectively (p<0.05). A PVPI >/= 3 and an extravascular lung
      water index/global end-diastolic index ratio >/= 1.8 x 10(-2) allowed the
      diagnosis of ALI/ARDS with a sensitivity of 85% and specificity of 100%.
      CONCLUSION: These results suggest that indexes of pulmonary permeability provided
      by transpulmonary thermodilution may be useful for determining the mechanism of
      pulmonary edema in the critically ill.

PMID- 17221192
TI  - An online monitoring system based on a synthetic sigma32-dependent tandem
      promoter for visualization of insoluble proteins in the cytoplasm of Escherichia
      coli.
AB  - The expression of heterologous proteins in the cytoplasm of Escherichia coli is
      often accompanied by limitations resulting in uncontrollable fermentation
      processes, increased rates of cell lysis, and thus limited yields of target
      protein. To deal with these problems, reporter tools are required to improve the
      folding properties of recombinant protein. In this work, the well-known sigma(32)
      dependent promoters ibpAB and fxsA were linked in a tandem promoter (ibpfxs),
      fused with the luciferase reporter gene lucA to allow enhanced monitoring of the
      formation of misfolded proteins and their aggregates in E. coli cells.
      Overexpression of MalE31, a folding-defective variant of the maltose-binding
      protein, and other partially insoluble heterologous proteins showed that the lucA
      reporter gene was activated in the presence of these misfolded proteins. Contrary
      to this, the absence of damaged proteins or overexpression of mostly soluble
      proteins led to a reduced level of luciferase induction. Through performing
      expression of aggregation-prone proteins, we were able to demonstrate that the
      ibpfxs::lucA reporter unit is 2.5-4.5 times stronger than the single reporter
      units ibp::lucA and fxs::lucA. Data of misfolding studies showed that this
      reporter system provides an adequate tool for in vivo folding studies in E. coli
      from microtiter up to fermentation scales.

PMID- 17221193
TI  - Molecular techniques for the early warning of toxic cyanobacteria blooms in
      freshwater lakes and rivers.
AB  - The aim of this work was to test the efficacy of molecular techniques for
      detecting toxigenic cyanobacteria in environmental water samples collected from
      freshwater lakes, rivers and reservoirs in Portugal. Of 26 environmental samples
      tested, 21 were found to contain Microcystis using a genus-specific polymerase
      chain reaction (PCR). Another primer pair was applied to the same DNA template to
      test for the presence of microcystin synthetase genes. This primer pair resulted
      in the formation of a PCR product in 15 of the samples containing Microcystis and
      one sample that did not give a positive result in the Microcystis genus-specific
      PCR. A restriction assay using the enzyme EcoRV was then applied to show that in
      most cases, the gene fragment was from toxigenic strains of Microcystis and, in
      one above-mentioned case, from a microcystin-producing strain of Planktothrix.
      All environmental samples were examined microscopically to confirm the presence
      of cyanobacteria species. Samples were also tested for the presence of
      microcystins using the ELISA plate assay. There was good agreement between the
      results obtained with molecular techniques and those obtained from microscopy and
      chemical methods. The PCR techniques applied in this paper were found to be
      useful, particularly when the concentration of the target organism was very low
      compared with other organisms. This technique can be used to detect inocula for
      cyanobacterial populations and therefore provide a useful tool for assessing
      under which conditions particular species can grow into bloom populations.

PMID- 17221194
TI  - Permeability issues in whole-cell bioprocesses and cellular membrane engineering.
AB  - Nutrient uptake and waste excretion are among the many important functions of the
      cellular membrane. While permitting nutrients into the cell, the cellular
      membrane system evolves to guide against noxious agents present in the
      environment from entering the intracellular milieu. The semipermeable nature of
      the membrane is at odds with biomolecular engineers in their endeavor of using
      microbes as cell factory. The cellular membrane often retards the entry of
      substrate into the cellular systems and prevents the product from being released
      from the cellular system for an easy recovery. Consequently, productivities of
      whole-cell bioprocesses such as biocatalysis, fermentation, and bioremediations
      are severely compromised. For example, the rate of whole-cell biocatalysis is
      usually 1-2 orders of magnitude slower than that of the isolated enzymes. When
      product export cannot keep pace with the production rate, intracellular product
      accumulation quickly leads to a halt of production due to product inhibition.
      While permeabilization via chemical or physical treatment of cell membrane is
      effective in small-scale process, large-scale implementation is problematic.
      Molecular engineering approach recently emerged as a much better alternative.
      Armed with increasingly sophisticated tools, biomolecular engineers are following
      nature's ingenuity to derive satisfactory solutions to the permeability problem.
      This review highlights these exciting molecular engineering achievements.

PMID- 17221195
TI  - L-tyrosine production by deregulated strains of Escherichia coli.
AB  - The excretion of the aromatic amino acid L: -tyrosine was achieved by
      manipulating three gene targets in the wild-type Escherichia coli K12: The
      feedback-inhibition-resistant (fbr) derivatives of aroG and tyrA were expressed
      on a low-copy-number vector, and the TyrR-mediated regulation of the aromatic
      amino acid biosynthesis was eliminated by deleting the tyrR gene. The generation
      of this L: -tyrosine producer, strain T1, was based only on the deregulation of
      the aromatic amino acid biosynthesis pathway, but no structural genes in the
      genome were affected. A second tyrosine over-producing strain, E. coli T2, was
      generated considering the possible limitation of precursor substrates. To enhance
      the availability of the two precursor substrates phosphoenolpyruvate and
      erythrose-4-phosphate, the ppsA and the tktA genes were over-expressed in the
      strain T1 background, increasing L: -tyrosine production by 80% in 50-ml batch
      cultures. Fed-batch fermentations revealed that L: -tyrosine production was
      tightly correlated with cell growth, exhibiting the maximum productivity at the
      end of the exponential growth phase. The final L: -tyrosine concentrations were
      3.8 g/l for E. coli T1 and 9.7 g/l for E. coli T2 with a yield of L: -tyrosine
      per glucose of 0.037 g/g (T1) and 0.102 g/g (T2), respectively.

PMID- 17221196
TI  - Susceptibility of staphylococcal biofilms to enzymatic treatments depends on
      their chemical composition.
AB  - Bacterial infections are serious complications after orthopaedic implant surgery.
      Staphylococci, with Staphylococcus epidermidis as a leading species, are the
      prevalent and most important species involved in orthopaedic implant-related
      infections. The biofilm mode of growth of these bacteria on an implant surface
      protects the organisms from the host's immune system and from antibiotic therapy.
      Therapeutic agents that disintegrate the biofilm matrix would release planktonic
      cells into the environment and therefore allow antibiotics to eliminate the
      bacteria. An addition of a biofilm-degrading agent to a solution used for washing
      draining procedures of infected orthopaedic implants would greatly improve the
      efficiency of the procedure and thus help to avoid the removal of the implant. We
      have previously shown that the extracellular staphylococcal matrix consists of a
      poly-N-acetylglucosamine (PNAG), extracellular teichoic acids (TAs) and protein
      components. In this study, we accessed the sensitivity of pre-formed biofilms of
      five clinical staphylococcal strains associated with orthopaedic prosthesis
      infections and with known compositions of the biofilm matrix to periodate,
      Pectinex Ultra SP, proteinase K, trypsin, pancreatin and dispersin B, an enzyme
      with a PNAG-hydrolysing activity. We also tested the effect of these agents on
      the purified carbohydrate components of staphylococcal biofilms, PNAG and TA. We
      found that the enzymatic detachment of staphylococcal biofilms depends on the
      nature of their constituents and varies between the clinical isolates. We suggest
      that a treatment with dispersin B followed by a protease (proteinase K or
      trypsin) could be capable to eradicate biofilms of a variety of staphylococcal
      strains on inert surfaces.

PMID- 17221197
TI  - Random segment deletion based on IS31831 and Cre/loxP excision system in
      Corynebacterium glutamicum.
AB  - A simple and random genome deletion method combining insertion sequence (IS)
      element IS31831 and the Cre/loxP excision system generated 42 Corynebacterium
      glutamicum mutants (0.2-186 kb). A total of 393.6 kb (11.9% of C. glutamicum R
      genome) coding for 331 genes was confirmed to be nonessential under standard
      laboratory conditions. The deletion strains, generated using only two vectors,
      varied not only in their lengths but also the location of the deletion along the
      C. glutamicum R genome. By comparing and analyzing the generated deletion
      strains, identification of nonessential genes, the roles of genes of hitherto
      unknown function, and gene-gene interactions can be easily and efficiently
      determined.

PMID- 17221198
TI  - The Arxula adeninivorans ATAL gene encoding transaldolase-gene characterization
      and biotechnological exploitation.
AB  - The yeast Arxula adeninivorans provides an attractive expression platform and can
      be exploited as gene source for biotechnologically interesting proteins. In the
      following study, a striking example for the combination of both aspects is
      presented. The transaldolase-encoding A. adeninivorans ATAL gene, including its
      promoter and terminator elements, was isolated and characterized. The gene
      includes a coding sequence of 963 bp encoding a putative 321 amino acid protein
      of 35.0 kDa. The enzyme characteristics analyzed from isolates of native strains
      and recombinant strains overexpressing the ATAL gene revealed a molecular mass of
      ca. 140 kDa corresponding to a tetrameric structure, a pH optimum of ca. 5.5, and
      a temperature optimum of 20 degrees C. The preferred substrates for the enzyme
      include D-erythrose-4-phosphate and D-fructose-6-phosphate, whereas D
      glyceraldehyde is not converted. The ATAL expression level under salt-free
      conditions was observed to increase in media supplemented with 5% NaCl rendering
      the ATAL promoter attractive for moderate heterologous gene expression under high
      salt conditions. Its suitability was assessed for the expression of a human serum
      albumin (HSA) reporter gene.

PMID- 17221199
TI  - Phospholipases and their industrial applications.
AB  - Phospholipids are present in all living organisms. They are a major component of
      all biological membranes, along with glycolipids and cholesterol. Enzymes aimed
      at modifying phospholipids, namely, phospholipases, are consequently widespread
      in nature, playing very diverse roles from aggression in snake venom to signal
      transduction and digestion in humans. In this review, we give a general overview
      of phospholipases A1, A2, C and D from a sequence and structural perspective and
      their industrial application. The use of phospholipases in industrial processes
      has grown hand-in-hand with our ability to clone and express the genes in
      microbial hosts with commercially attractive amounts. Further, the use in
      industrial processes is increasing by optimizing the enzymes by protein
      engineering. Here, we give a perspective on the work done to date to express
      phospholipases in heterologous hosts and the efforts to optimize them by protein
      engineering. We will draw attention to the industrial processes where
      phospholipases play a key role and show how the use of a phospholipase for oil
      degumming leads to substantial environmental benefits. This illustrates a very
      general trend: the use of enzymes as an alternative to chemical processes to make
      products often provides a cleaner solution for the industrial processes. In a
      world with great demands on non-polluting, energy saving technical solutions-
      white biotechnology is a strong alternative.

PMID- 17221200
TI  - Characterization of the new beta-glucuronidase from Streptococcus equi subsp.
      zooepidemicus.
AB  - Recently, a new gene encoding beta-glucuronidase from Streptococcus equi subsp.
      zooepidemicus (SEZ) was identified and expressed in Escherichia coli. In this
      paper, the characterization of the enzyme is described. Specific enzyme activity
      was 120,000 U/mg purified protein at 37 degrees C and pH = 7.0. The temperature
      and pH value, at which the enzyme has the highest specific activity, were
      determined and were found to be approximately 52 degrees C and 5.6, respectively.
      The mutant strain SEZ glcHis was designed for the efficient isolation of beta
      glucuronidase from S. equi subsp. zooepidemicus. It was observed that the
      specific activity of beta-glucuronidase in the cytoplasmic extract of a mutated
      strain was about 45% lower than in the cytoplasmic extract of a wild-type strain.
      The specific activity of purified beta-glucuronidase from SEZ glcHis was four
      times as low as beta-glucuronidase purified from E. coli. Comparing the specific
      activity of purified streptococcal beta-glucuronidase from E. coli with E. coli
      beta-glucuronidase (the enzyme with the highest specific activity was supplied by
      Sigma), the former is 1.8 higher than the latter.

PMID- 17221202
TI  - Purification and characterization of fibrinolytic alkaline protease from Fusarium
      sp. BLB.
AB  - Fusarium sp. BLB, which produces a strongly fibrinolytic enzyme, was isolated
      from plant leaf (Hibiscus). Fibrinolytic alkaline protease was purified from a
      culture filtrate of Fusarium sp. BLB by precipitation with (NH4)2(SO4) and column
      chromatography with CM-Toyopearl 650 M and Superdex 75. The purified enzyme was
      homogeneous on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS
      PAGE). The molecular weight was 27,000 by SDS-PAGE. Maximum activity of protease
      was observed at pH 9.5 and 50 degrees C. Purified protease was active between pH
      2.5 and 11.5 and was found to be stable up to 50 degrees C. The enzyme derived
      from Fusarium sp. BLB is useful for thrombolytic therapy because this enzyme
      showed pH resistance. The activity was inhibited by diisopropylfluorophosphate
      and phenylmethylsulfonyl fluoride. The N-terminal amino acid sequence of the
      enzyme showed a similarity to those of proteases from Fusarium sp., Streptomyces
      griseus, Bos taurus bovine, Katsuwo pelamis digestive tract, and Lumbricus
      rubellus.

PMID- 17221204
TI  - Nuclear beta-catenin accumulation associates with epithelial morphogenesis in
      craniopharyngiomas.
AB  - Activation of the Wnt/wingless signalling cascade is a key mechanism in
      developmental morphogenesis, whereas aberrant nuclear accumulation of beta
      catenin in adult tissues seems to be associated with neoplastic transformation
      and tumour progression. Adamantinomatous craniopharyngiomas carry activating
      mutations in exon 3 of the beta-catenin gene, which results in a distinct pattern
      of nuclear beta-catenin accumulation in up to 95% of respective tumour specimens.
      To better characterise the impact of nuclear beta-catenin aggregation in these
      neoplasms, we systematically examined epithelial differentiation and cell cycle
      associated molecules in accumulating compared to non-accumulating tumour cell
      clusters using a cohort of 65 adamantinomatous craniopharyngiomas. Monoclonal
      antibodies directed against cytokeratins 5/6 (CK5/6) were utilised to
      differentiate squamous from simple epithelium, the latter being identified by
      immunoreactivity for cytokeratins 8 and 18 (CK8/CK18). Intriguingly, nuclear beta
      catenin accumulation in whorl-like tumour cell clusters was always associated
      with a distinct CK8 and CK18 immunoreactivity, whereas surrounding non
      accumulating tumour cells showed exclusively squamous differentiation indicated
      by CK5/6 expression. In addition, a low proliferation activity combined with an
      increased expression of p21(WAF1/CIP1), a key control protein of the cell cycle,
      was observed in beta-catenin accumulating cells. Our data support an impact of
      nuclear beta-catenin on different cytoarchitectural and epithelial
      differentiation patterns in adamantinomatous craniopharyngiomas.

PMID- 17221205
TI  - Expression patterns of LIS1, dynein and their interaction partners dynactin,
      NudE, NudEL and NudC in human gliomas suggest roles in invasion and
      proliferation.
AB  - Diffusely infiltrating gliomas are the most common type of primary intracranial
      neoplasm in humans. One of the major obstacles to the effective treatment of
      these tumors is their highly infiltrative growth. However, mechanisms controlling
      their migration and proliferation are poorly understood. Glioma cells resemble
      neural progenitors, and we hypothesize that gliomas recapitulate the capacity of
      migration and proliferation of progenitors that takes place during brain
      development. Based on recent evidence implicating cytoplasmic dynein and its
      regulatory proteins in neural progenitor migration and division, we conducted
      immunohistochemical evaluation of surgically resected human glioma samples for
      the presence and distribution of these proteins. We examined expression of LIS1,
      the gene responsible for type I lissencephaly, cytoplasmic dynein and the dynein-
      and LIS1-interacting factors dynactin, NudE/NudEL and NudC, which play
      significant roles in neural progenitor cell behavior. We found that each of these
      proteins is expressed in all histological types and grades of human
      neuroectodermal tumors examined. Immunohistochemical analysis revealed that the
      levels of expression varied from cell to cell within each tumor, ranging from
      very high to undetectable. This stands in contrast to the low levels of diffuse
      staining seen in non-neoplastic brain tissue. Of particular interest, we noted
      tumor cells infiltrating the white matter and tumor cells undergoing cell
      division amongst the cells with notably high expression levels. These findings
      are compatible with the idea that LIS1 and its interacting proteins play a role
      in glioma migration and proliferation analogous to their role during brain
      development.

PMID- 17221203
TI  - A new clinico-pathological classification system for mesial temporal sclerosis.
AB  - We propose a histopathological classification system for hippocampal cell loss in
      patients suffering from mesial temporal lobe epilepsies (MTLE). One hundred and
      seventy-eight surgically resected specimens were microscopically examined with
      respect to neuronal cell loss in hippocampal subfields CA1-CA4 and dentate gyrus.
      Five distinct patterns were recognized within a consecutive cohort of
      anatomically well-preserved surgical specimens. The first group comprised
      hippocampi with neuronal cell densities not significantly different from age
      matched autopsy controls [no mesial temporal sclerosis (no MTS); n = 34, 19%]. A
      classical pattern with severe cell loss in CA1 and moderate neuronal loss in all
      other subfields excluding CA2 was observed in 33 cases (19%), whereas the vast
      majority of cases showed extensive neuronal cell loss in all hippocampal
      subfields (n = 94, 53%). Due to considerable similarities of neuronal cell loss
      patterns and clinical histories, we designated these two groups as MTS type 1a
      and 1b, respectively. We further distinguished two atypical variants
      characterized either by severe neuronal loss restricted to sector CA1 (MTS type
      2; n = 10, 6%) or to the hilar region (MTS type 3, n = 7, 4%). Correlation with
      clinical data pointed to an early age of initial precipitating injury (IPI < 3
      years) as important predictor of hippocampal pathology, i.e. MTS type 1a and 1b.
      In MTS type 2, IPIs were documented at a later age (mean 6 years), whereas in MTS
      type 3 and normal appearing hippocampus (no MTS) the first event appeared beyond
      the age of 13 and 16 years, respectively. In addition, postsurgical outcome was
      significantly worse in atypical MTS, especially MTS type 3 with only 28% of
      patients having seizure relief after 1-year follow-up period, compared to
      successful seizure control in MTS types 1a and 1b (72 and 73%). Our
      classification system appears suitable for stratifying the clinically
      heterogeneous group of MTLE patients also with respect to postsurgical outcome
      studies.

PMID- 17221206
TI  - Ehlers-Danlos syndrome (EDS) type IV: review of the literature.
AB  - Ehlers-Danlos syndrome (EDS) is a heterogeneous group of connective tissue
      heritable disorders. EDS type IV is a rare form that presents typical clinical
      signs, such as easy bruising and haematomas at sites of trauma, skin
      manifestations (translucent skin with visible veins), and joint hyperlaxity. To
      illustrate the dermatological features and describe an aggressive periodontitis,
      a symptom not yet reported in this EDS type, we present a case of a 23-year-old
      young man. This patient has been suffering from bruised skin, haematomas, and
      varicose veins in his legs. These lesions, typical of EDS type IV, were
      associated with trauma followed by slow and difficult cicatrization. Teeth loss
      and clinical attachment loss in all the remaining teeth, a symptom compatible
      with a severe destruction of the periodontal support, was reported after
      orthodontic treatment. The treatment is limited to control the disease and teeth
      loss. Considering this new clinical symptom associated with EDS type IV, we
      suggest that the use of orthodontic apparatus should be carefully considered in
      such patients.

PMID- 17221207
TI  - Imaging by multiple modalities of patients with a carotidynia syndrome.
AB  - The purpose of this article is to familiarize readers with the clinical syndrome
      of carotidynia. In the past, the International Headache Society (IHS) described
      idiopathic carotidynia as a diagnostic entity consisting of a self-limiting neck
      pain syndrome and tenderness over the carotid bifurcation without structural
      abnormality and then recently removed it from its classification. Although the
      clinical criteria of carotidynia in the former classification of the IHS included
      the absence of structural abnormality, several publications have demonstrated
      associated radiological findings and have described the usefulness of
      radiological investigations in diagnosing this syndrome. In this paper, we report
      four additional cases with a carotidynia clinical syndrome (according to the
      former classification) and the presence of abnormal soft tissue infiltration
      surrounding the symptomatic carotid artery as demonstrated by multiple imaging
      modalities, without any other underlying cause for the carotid pain syndrome. Our
      findings support the hypothesis that carotidynia could be a distinct disease
      entity, possibly caused by inflammation.

PMID- 17221201
TI  - Expressed sequence tags-based identification of genes in the biocontrol agent
      Chaetomium cupreum.
AB  - Chaetomium cupreum has a potential as biocontrol agent against a range of plant
      pathogens on the basis of production of antifungal metabolites, mycoparasitism,
      competition for space and nutrients, or various combinations of these. To explore
      genes expressed in C. cupreum, a cDNA library was constructed from mycelium and
      3,066 expressed sequence tags (ESTs) were generated. Clusters analysis enabled
      the identification of 1,471 unigenes with 392 contigs and 1,079 singleton
      sequences. Putative functions were assigned to 874 unigenes that exhibited strong
      similarity to genes/ESTs in public databases putatively containing genes involved
      in cellular component, molecular function, and biological process. Other 597 ESTs
      representing novel genes showed no significant similarity to public database
      resource of NCBI. A proportion of genes was identified related to degradation of
      pathogen cell wall, antifungal metabolite production, as was estimated in the
      biocontrol fungus. The paper described is a first step towards the knowledge of
      the C. cupreum genome. The results present the useful application of EST analysis
      on C. cupreum and provide a preliminary indication of gene expression putatively
      involved in biocontrol.

PMID- 17221209
TI  - Studies of the associations between functional beta2-adrenergic receptor variants
      and obesity, hypertension and type 2 diabetes in 7,808 white subjects.
AB  - AIMS/HYPOTHESIS: Functional and common Arg16Gly and Gln27Glu polymorphisms have
      been identified in ADRB2, the gene encoding the beta2-adrenergic receptor. These
      variants have previously been examined for association with obesity, hypertension
      and diabetes with inconclusive results. MATERIALS AND METHODS: We investigated
      both of these variants in 7,808 unrelated, middle-aged white people for their
      association with obesity in a case-control study, quantitative trait analysis and
      meta-analysis. Moreover, both variants were investigated for their potential
      influence on measures of hypertension and type 2 diabetes by case-control and
      quantitative trait analyses. RESULTS: The present study did not find consistent
      evidence for an association of these beta2-adrenergic receptor variants with
      obesity or hypertension; neither did the quantitative trait analyses show any
      effect of the variants on obesity-related traits. However, both the Gly allele of
      the Arg16Gly variant and the Glu allele of the Gln27Glu variant showed nominal
      association with systolic blood pressure. Furthermore, there was a nominal
      association of the Arg16 allele frequency and genotype distribution with type 2
      diabetes; however, no influence on quantitative biochemical phenotypes related to
      type 2 diabetes was found. A nominal association of the Arg/Gly genotype with the
      metabolic syndrome was also observed (p=0.003). Logistic regression analyses
      provided no evidence of a synergistic or an additive effect of these variants on
      obesity, hypertension or diabetes. CONCLUSIONS/INTERPRETATION: After studying
      7,808 middle-aged white subjects, we were unable to demonstrate any consistent
      associations between two common amino acid polymorphisms of the beta2-adrenergic
      receptor and obesity, hypertension or type 2 diabetes.

PMID- 17221208
TI  - Thioguanin-induced nodular regenerative hyperplasia of the liver-ROC analysis of
      different MR techniques.
AB  - The aim of this study was to evaluate the diagnostic value of different magnetic
      resonance (MR) techniques for the diagnosis of nodular regenerative hyperplasia
      (NRH). Thirty-one patients with inflammatory bowel disease, who received 6
      thioguanin, underwent liver biopsy and liver MRI on a 1.5-T MR system, with
      gadolinium and superparamagnetic iron oxide particles (SPIO). MR imaging (MRI)
      was evaluated independently as well as in consensus by two blinded readers, who
      received the following image sets: pre-contrast; pre-contrast and gadolinium
      enhanced; pre-contrast and SPIO-enhanced and all images. The results were
      correlated with histopathology and diagnostic efficacy parameters were
      calculated. NRH was found in 13/31 patients. The set "all images" showed the
      highest sensitivity (84.6%), accuracy (77.4%) and negative predictive value
      (86.7%). However, results for gadolinium were only slightly inferior. The highest
      specificity (76.5%) was found for SPIO. The A(z) values of both readers were
      highest for gadolinium (mean A(z) = 0.824). It can be concluded that gadolinium
      enhanced and SPIO-enhanced MRI enable an accurate diagnosis of NRH. Since
      gadolinium-enhanced MRI is very sensitive, it should be used for screening high
      risk patients. SPIO-enhanced MRI is less sensitive, but more specific. The
      combination of both guarantees a high sensitivity and specificity and, therefore,
      is the diagnostic procedure of choice.

PMID- 17221210
TI  - Regulation of pancreatic endocrine cell differentiation by sulphated
      proteoglycans.
AB  - AIMS/HYPOTHESIS: Epithelium-mesenchyme interactions play a major role in pancreas
      development. Recently, we demonstrated that embryonic pancreatic mesenchyme
      enhanced progenitor cell proliferation but inhibited endocrine cell
      differentiation. Here, we investigated the role played by sulphated
      proteoglycans, which are known to be essential to embryonic development, in this
      inhibitory effect. MATERIALS AND METHODS: We first determined the expression of
      the genes encoding glypicans, syndecans and the main glycosaminoglycan chain
      modifying enzymes in immature embryonic day (E) 13.5 and more differentiated
      E17.5 rat pancreases. Next, using an in vitro model of pancreas development, we
      blocked the action of endogenous sulphated proteoglycans by treating embryonic
      pancreases in culture with chlorate, an inhibitor of proteoglycan sulphation, and
      examined the effects on pancreatic endocrine cell differentiation. RESULTS: We
      first showed that expression of the genes encoding glypicans 1, 2, 3 and 5 and
      heparan sulphate 2-sulfotransferase decreased between E13.5 and E17.5. We next
      found that alteration of proteoglycan action by chlorate blocked the inhibitory
      effect of the mesenchyme on endocrine differentiation. Chlorate-treated
      pancreases exhibited a dramatic increase in beta cell number in a dose-dependent
      manner (169-and 375-fold increase with 30 mmol/l and 40 mmol/l chlorate,
      respectively) and in alpha cell development. Insulin-positive cells that
      developed in the presence of chlorate exhibited a phenotype of mature cells with
      regard to the expression of the following genes: pancreatic and duodenal homeobox
      gene 1 (Pdx1), proprotein convertase subtilisin/kexin type 1 (Pcsk1; previously
      known as pro-hormone convertase 1/3), proprotein convertase subtilisin/kexin type
      2 (Pcsk2; previously known as pro-hormone convertase 2) and solute carrier family
      2 (facilitated glucose transporter), member 2 (Slc2a1; previously known as
      glucose transporter 2). Finally, we showed that chlorate activated endocrine cell
      development by inducing neurogenin 3 (Neurog3) expression in early endocrine
      progenitor cells. CONCLUSIONS/INTERPRETATION: We demonstrated that sulphated
      proteoglycans control pancreatic endocrine cell differentiation. Understanding
      the mechanism by which sulphated proteoglycans affect beta cell development could
      be useful in the generation of beta cells from embryonic stem cells.

PMID- 17221211
TI  - Macrophages and dendritic cells infiltrating islets with or without beta cells
      produce tumour necrosis factor-alpha in patients with recent-onset type 1
      diabetes.
AB  - AIMS/HYPOTHESIS: Type 1A diabetes results from autoimmune destruction of
      pancreatic beta cells. We examined the involvement of TNF-alpha and IL-1beta, as
      well as of T cells, macrophages and dendritic cells, in the destruction of beta
      cells in patients with recent-onset type 1 diabetes. MATERIALS AND METHODS: We
      obtained pancreatic biopsy specimens from six patients with recent-onset type 1
      diabetes and analysed these by immunohistochemistry. RESULTS: T cell infiltration
      was less common in islets without beta cells (12.5 [0-33.3]%) than in those with
      beta cells (46.0 [17.4-83.3]%), while macrophages and dendritic cells showed a
      similar extent of infiltration into islets both with or without beta cells. TNF
      alpha was detected in 25.0 (4.3-46.9)% of macrophages and 11.8 (0-40.0)% of
      dendritic cells infiltrating the islets in samples from each patient, but not at
      all in T cells. IL-1beta was detected in 1.8 (0-11.3)% of T cells infiltrating
      the islets with beta cells, while it was found in 19.2 (0-35.3)% of macrophages
      or 10.7 (0-31.3)% of dendritic cells infiltrating the islets in samples from each
      patient (all values median [range]). CONCLUSIONS/INTERPRETATION: Macrophages and
      dendritic cells infiltrate the islets and produce inflammatory cytokines (TNF
      alpha and IL-1beta) during the development of type 1A diabetes.

PMID- 17221212
TI  - Adiposity, physical fitness and incident diabetes: the physical activity
      longitudinal study.
AB  - AIMS/HYPOTHESIS: The purpose of this study was to investigate the relationships
      among adiposity, physical activity, physical fitness and the development of
      diabetes in a diverse sample of Canadians. METHODS: The sample included 1,543
      adults (709 men and 834 women) from the Canadian Physical Activity Longitudinal
      Study who were free of diabetes at baseline (1988). Several indicators of
      adiposity (BMI, waist circumference, WHR, sum of skinfold thicknesses),
      musculoskeletal fitness (sit-ups, push-ups, grip strength, trunk flexibility),
      cardiorespiratory fitness (maximal metabolic equivalents [METs]) and leisure-time
      physical activity levels were measured at baseline. Participants were followed
      until 2002-2004 for the ascertainment of new cases of diabetes. RESULTS: The 15.5
      year cumulative incidence of diabetes was 5.0% (5.2% in men, 4.9% in women).
      Adiposity and physical fitness, but not physical activity, were significant
      predictors of diabetes after adjustment for age, sex and several covariates. For
      each standard deviation of the indicators of adiposity, the risk of diabetes was
      99-194% higher. Conversely, the risk was 70 and 61% lower for each standard
      deviation of maximal METs and composite musculoskeletal fitness score,
      respectively. Receiver operating characteristic curve analyses confirmed that
      neither adiposity nor physical fitness provided a superior prediction of incident
      diabetes. CONCLUSIONS/INTERPRETATION: Adiposity and physical fitness were both
      important predictors of the development of diabetes in this cohort of Canadians.

PMID- 17221213
TI  - How much insulin is enough? A quantitative assessment of the transdifferentiaton
      potential of liver.

PMID- 17221214
TI  - Adenoviral overproduction of interleukin-1 receptor antagonist increases beta
      cell replication and mass in syngeneically transplanted islets, and improves
      metabolic outcome.
AB  - AIMS/HYPOTHESIS: Interleukin-1 receptor antagonist (IL1RN, also known as IL1RA)
      is a naturally occurring inhibitor of IL-1 action and its overproduction protects
      pancreatic islets from the deleterious effects of IL-1beta on beta cell
      replication, apoptosis and function. The aim of this study was to determine
      whether viral gene transfer of the Il1rn gene into rat islets ex vivo had a
      beneficial effect on the outcome of the graft. MATERIALS AND METHODS:
      Streptozotocin-diabetic Lewis rats were syngeneically transplanted with 500 or
      800 Ad-Il1rn-infected or uninfected islets. Islet grafts were collected on day 3,
      10 or 28 after transplantation and beta cell apoptosis, replication, size and
      mass were determined. RESULTS: Animals transplanted with 500 islets remained
      hyperglycaemic throughout the follow-up, as expected. Beta cell replication
      increased in the Ad-Il1rn group on days 3, 10 and 28 after transplantation
      compared with normal pancreas. In uninfected islets, by contrast, beta cell
      replication was increased only on day 10. Beta cell apoptosis was increased in
      all transplanted groups; it was 25% lower in the Ad-Il1rn than in uninfected
      groups, but differences were not statistically significant. The initially
      transplanted beta cell mass was reduced on day 3, increasing subsequently in Ad
      Il1rn grafts, but not in uninfected grafts. When 800 islets were transplanted,
      all animals grafted with Ad-Il1rn-infected islets, but only 40% of those
      transplanted with uninfected islets, achieved normoglycaemia 14 days after
      transplantation. CONCLUSIONS/INTERPRETATION: Overproduction of IL1RN increased
      beta cell replication and mass of islet grafts and reduced the beta cell number
      required to achieve normoglycaemia.

PMID- 17221216
TI  - Angiogenic activity in patients with psoriasis is significantly decreased by
      Goeckerman's therapy.
AB  - Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy
      grade coal tar on affected skin with subsequent exposure to UV light.
      Goeckerman's therapy is still the first line therapy of psoriasis in the Czech
      Republic because of its low cost and long-term efficacy. Disturbances in
      angiogenic activity are characteristic for the immunopathogenesis of psoriasis.
      An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is
      produced by keratinocytes and inflammatory cells in patients suffering from the
      disease. The aim of this study was to evaluate the influence of GT of psoriasis
      on angiogenic activities by comparing serum levels of vascular endothelial growth
      factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with
      psoriasis in peripheral blood samples collected before and after therapy. Forty
      otherwise healthy blood donors serve as a control group. The efficacy of GT was
      delineated by psoriasis area and severity index (PASI). The disease activity was
      significantly diminished by GT (P < 0.001). The serum levels of both VEGF and
      bFGF were statistically significantly correlated to PASI value in patients before
      the treatment by GT. The serum levels of VEGF (329.4 +/- 125.5 microg/ml) and
      bFGF (10.2 +/- 5.04 pg/ml) in patients before GT were significantly higher than
      those measured in healthy blood donors (VEGF 236.4 +/- 55.9 pg/ml, bFGF 7.3 +/-
      3.7 pg/ ml). The serum levels of both VEGF and bFGF were significantly diminished
      by GT. The level of VEGF dropped from 329.4 +/- 125.5 pg/ml before GT to 278.5 +/
      109.9 pg/ml after GT (P = 0.0042) and the level of bFGF fell from 10.2 +/- 5.04
      to 7.78 +/- 4.5 pg/ml (P = 0.019). Comparing to healthy controls, the serum level
      of bFGF in psoriasis patients was normalised (P = 0.5723) after GT. In contrast,
      the serum level of VEGF remained significantly increased in psoriasis patients
      after GT in comparison with healthy blood donors (P = 0.0319). In conclusion, we
      found that the angiogenic potential which is abnormally increased in patients
      with psoriasis is significantly alleviated by GT.

PMID- 17221215
TI  - Serologic and immunohistochemical prognostic biomarkers of cutaneous
      malignancies.
AB  - Biomarkers are important tools in clinical diagnosis and prognostic
      classification of various cutaneous malignancies. Besides clinical and
      histopathological aspects (e.g. anatomic site and type of the primary tumour,
      tumour size and invasion depth, ulceration, vascular invasion), an increasing
      variety of molecular markers have been identified, providing the possibility of a
      more detailed diagnostic and prognostic subgrouping of tumour entities, up to
      even changing existing classification systems. Recently published gene expression
      or proteomic profiling data relate to new marker molecules involved in skin
      cancer pathogenesis, which may, after validation by suitable studies, represent
      future prognostic or predictive biomarkers in cutaneous malignancies. We, here,
      give an overview on currently known serologic and newer immunohistochemical
      biomarker molecules in the most common cutaneous malignancies, malignant
      melanoma, squamous cell carcinoma and cutaneous lymphoma, particularly
      emphasizing their prognostic and predictive significance.

PMID- 17221217
TI  - VEP asymmetry with ophthalmological and MRI findings in two achiasmatic children.
AB  - Achiasmia is a rarely diagnosed visual pathway maldevelopment where all or the
      majority of nasal retinal fibres fail to decussate at the optic chiasm. It has
      been identified by neuroimaging and also by visual evoked potential (VEP)
      asymmetry. VEP asymmetry has not been defined consistently in previous studies.
      The aim was to study VEP asymmetry to flash stimulation in two children with
      maldevelopment of the optic chiasm in comparison to control children. Both
      children had congenital nystagmus, optic nerve hypoplasia with a bilateral small
      double ring, bitemporal visual field defect and normal colour vision. In child 1
      visual acuity in both eyes was 0.1, in child 2 it was 0.2. MRI showed reduced
      chiasmal size in child 1, while in child 2 it was combined with other midline
      abnormalities. VEP to monocular flash stimulation showed in both children
      distinctive occipital distribution, which was not observed in control children.
      The N2 wave was distributed asymmetrically over the ipsilateral hemisphere to the
      stimulated eye, while the P2 wave was distributed over both hemispheres. The P2
      wave was however better defined over the ipsilateral hemisphere. Flash VEP
      occipital distribution remained similar in child 1, who was followed from 10
      months to 9 years. These cases of achiasmia demonstrate a distinctive VEP
      asymmetry in the distribution of the flash VEP N2 wave, as well as the expected
      structural defect determined by neuroimaging.

PMID- 17221218
TI  - The CCHCR1 (HCR) gene is relevant for skin steroidogenesis and downregulated in
      cultured psoriatic keratinocytes.
AB  - The HCR gene, officially called Coiled-Coil alpha-Helical Rod protein 1 (CCHCR1),
      located within the major psoriasis susceptibility locus PSORS1, is a plausible
      candidate gene for the risk effect. Recently, CCHCR1 was shown to promote
      steroidogenesis by interacting with the steroidogenic acute regulator protein
      (StAR). Here, we examined the role of CCHCR1 in psoriasis and cutaneous steroid
      metabolism. We found that CCHCR1 and StAR are expressed in basal keratinocytes in
      overlapping areas of the human skin, and CCHCR1 stimulated pregnenolone
      production in steroidogenesis assay. Overexpression of either the CCHCR1*WWCC
      risk allele or the non-risk allele enhanced steroid synthesis in vitro.
      Furthermore, the cytochrome P450scc enzyme was expressed in human keratinocytes
      and was induced by forskolin, a known activator of steroidogenesis, and forskolin
      also upregulated CCHCR1. CCHCR1 has an altered expression pattern in lesional
      psoriatic skin compared to normal healthy skin, suggesting its dysregulation in
      psoriasis. We found that the expression of CCHCR1 is downregulated twofold at the
      mRNA level in cultured non-lesional psoriatic keratinocytes when compared to non
      psoriatic healthy cells. Our results also suggest a connection between CCHCR1 and
      vitamin D metabolism in keratinocytes. The expression of the vitamin D receptor
      (VDR) gene was lower in non-lesional psoriatic keratinocytes than in healthy
      cells. Furthermore, Vdr expression was downregulated in the keratinocytes of mice
      overexpressing the CCHCR1*WWCC risk allele when compared to keratinocytes from
      mice with the non-risk allele of CCHCR1. Finally, we demonstrate that other
      agents relevant for psoriasis and/or the regulation of steroidogenesis influence
      CCHCR1 expression in keratinocytes, including insulin, EGF, cholesterol,
      estrogen, and cyclosporin A. Taken the role of steroid hormones, including
      vitamin D and estrogen, in cell proliferation, epidermal barrier homeostasis,
      differentiation, and immune response, our results suggest a role for CCHCR1 in
      the pathogenesis of psoriasis via the regulation of skin steroid metabolism.

PMID- 17221220
TI  - Vestibular inputs do not influence the fusimotor system in relaxed muscles of the
      human leg.
AB  - Descending vestibular pathways have been shown to influence recruitment
      thresholds of alpha motoneurones in both human and cat. However, whereas parallel
      connections to the fusimotor system have been shown in the cat, such connections
      have not yet been demonstrated in humans. In the present study we investigated
      whether vestibular inputs can influence the firing of spontaneously active muscle
      spindles in the leg via activation of gamma motoneurones. Unitary recordings were
      made from 30 muscle spindle afferents via tungsten microelectrodes inserted
      percutaneously into the common peroneal nerve of seated awake human subjects.
      Sinusoidal bipolar binaural galvanic vestibular stimulation (GVS; frequency 0.2,
      0.5, 0.8 Hz, amplitude +/-2 mA, 100 cycles) was applied to the mastoid processes.
      This continuous stimulation produced a sustained frequency-dependent illusion of
      "rocking in a boat" or "swinging in a hammock". Despite these robust illusions
      none of the spontaneously active muscle spindles exhibited phase-locked
      modulation of firing during sinusoidal GVS. We conclude that this dynamic
      vestibular input was not sufficient to recruit gamma motoneurones, which are
      known to have little spontaneous activity in relaxed human muscles.

PMID- 17221221
TI  - Travel distance estimation from visual motion by leaky path integration.
AB  - Visual motion can be a cue to travel distance when the motion signals are
      integrated. Distance estimates from visually simulated self-motion are imprecise,
      however. Previous work in our labs has given conflicting results on the
      imprecision: experiments by Frenz and Lappe had suggested a general
      underestimation of travel distance, while results from Redlick, Jenkin and Harris
      had shown an overestimation of travel distance. Here we describe a collaborative
      study that resolves the conflict by tracing it to differences in the tasks given
      to the subjects. With an identical set of subjects and identical visual motion
      simulation we show that underestimation of travel distance occurs when the task
      involves a judgment of distance from the starting position, and that
      overestimation of travel distance occurs when the task requires a judgment of the
      remaining distance to a particular target position. We present a leaky integrator
      model that explains both effects with a single mechanism. In this leaky
      integrator model we introduce the idea that, depending on the task, either the
      distance from start, or the distance to target is used as a state variable. The
      state variable is updated during the movement by integration over the space
      covered by the movement, rather than over time. In this model, travel distance
      mis-estimation occurs because the integration leaks and because the
      transformation of visual motion to travel distance involves a gain factor. Mis
      estimates in both tasks can be explained with the same leak rate and gain in both
      conditions. Our results thus suggest that observers do not simply integrate
      traveled distance and then relate it to the task. Instead, the internally
      represented variable is either distance from the origin or distance to the goal,
      whichever is relevant.

PMID- 17221219
TI  - The Fanconi anemia (FA) pathway confers glioma resistance to DNA alkylating
      agents.
AB  - DNA alkylating agents including temozolomide (TMZ) and 1,3-bis[2-chloroethyl]-1
      nitroso-urea (BCNU) are the most common form of chemotherapy in the treatment of
      gliomas. Despite their frequent use, the therapeutic efficacy of these agents is
      limited by the development of resistance. Previous studies suggest that the
      mechanism of this resistance is complex and involves multiple DNA repair
      pathways. To better define the pathways contributing to the mechanisms underlying
      glioma resistance, we tested the contribution of the Fanconi anemia (FA) DNA
      repair pathway. TMZ and BCNU treatment of FA-proficient cell lines led to a dose-
      and time-dependent increase in FANCD2 mono-ubiquitination and FANCD2 nuclear foci
      formation, both hallmarks of FA pathway activation. The FA-deficient cells were
      more sensitive to TMZ/BCNU relative to their corrected, isogenic counterparts. To
      test whether these observations were pertinent to glioma biology, we screened a
      panel of glioma cell lines and identified one (HT16) that was deficient in the FA
      repair pathway. This cell line exhibited increased sensitivity to TMZ and BCNU
      relative to the FA-proficient glioma cell lines. Moreover, inhibition of FA
      pathway activation by a small molecule inhibitor (curcumin) or by small
      interference RNA suppression caused increased sensitivity to TMZ/BCNU in the U87
      glioma cell line. The BCNU sensitizing effect of FA inhibition appeared additive
      to that of methyl-guanine methyl transferase inhibition. The results presented in
      this paper underscore the complexity of cellular resistance to DNA alkylating
      agents and implicate the FA repair pathway as a determinant of this resistance.

PMID- 17221222
TI  - Muscle modes and synergies during voluntary body sway.
AB  - We studied the coordination of muscle activity during voluntary body sway
      performed by human subjects at different frequencies. Subjects stood on the force
      platform and performed cyclic shifts of the center of pressure (COP) while being
      paced by the metronome. A major question was: does the makeup of muscle synergies
      and their ability to assure reproducible sway trajectory vary with the speed of
      the sway? Principal component analysis was used to identify three muscle groups
      (M-modes) within the space of integrated indices of muscle activity. M-mode
      vectors were similar across both subjects and sway frequencies. There were also
      similar relations between changes in the magnitudes of all three M-modes and COP
      shifts (the Jacobians) across the sway frequencies. Variance in the M-mode space
      across sway cycles was partitioned into two components, one that did not affect
      the average value of COP shift ("good variance") and the other that did. An index
      (DeltaV) was computed reflecting the relative amount of the "good variance"; this
      index has been interpreted as reflecting a multi-M-mode synergy stabilizing the
      COP trajectory. The average value of DeltaV was similar across all sway
      frequencies; DeltaV showed a within-a-cycle modulation at low but not at high
      sway frequencies. The modulation was mostly due to variations in the "good
      variance". We conclude that muscle modes and their mapping on COP shifts are
      robust across a wide range of rates of COP shifts. Multi-M-mode synergies
      stabilize COP shifts (assure its reproducibility) within a wide range of its
      speeds, but only during cyclic COP changes. Taken together with earlier studies
      that showed weak or absent multi-M-mode synergies during fast discrete COP
      shifts, the results suggest a basic difference between the neural control
      assuring stability of steady-state processes (postural or oscillatory) and
      transient processes (such as discrete actions). Current results provide the most
      comprehensive support for the notion of multi-M-mode synergies stabilizing time
      profiles of important performance variables in motor tasks involving large muscle
      groups.

PMID- 17221223
TI  - The contribution of the human PPC to the orienting of visuospatial attention
      during smooth pursuit.
AB  - Smooth pursuit eye movements function to stabilize the retinal image of small
      moving targets. In order for those targets to be foveated, however, they must
      first be "captured" by an attentional mechanism which then interacts with the
      oculomotor system. Cortical sites involved with producing smooth pursuit overlap
      with areas known to be involved in directing visuospatial attention, particularly
      the posterior parietal cortex (PPC). The goal of the current study was to
      characterize the contributions made by the left and right posterior parietal
      cortices (lPPC and rPPC) to the interaction between visuospatial attention and
      the generation of smooth pursuit eye movements. Transcranial magnetic stimulation
      (TMS) was used to temporarily disrupt each area at different times around target
      motion onset in a pursuit task that explicitly manipulated the covert orienting
      of attention. TMS over the lPPC, rPPC and a control site (the vertex) evoked a
      similar pattern of results, in that the earlier TMS delivery times caused a
      reduced pursuit latency compared to baseline measures, while TMS immediately
      prior to target motion onset resulted in latencies slower than baseline. In
      addition, however, TMS over the lPPC and rPPC (but not the vertex) preferentially
      influenced the generation of contralateral pursuit, with the lPPC doing so in a
      relatively time-independent manner, and the rPPC doing so in a time-dependent
      manner. This pattern of results implies that both the left and right PPC are
      directly involved in the interaction between attention and smooth pursuit
      preparation.

PMID- 17221224
TI  - Sugars proportionately affect artemisinin production.
AB  - Little is known about the effect of sugars in controlling secondary metabolism.
      In this study, sugars alone or in combination with their analogs were used to
      investigate their role in the production of the antimalarial drug, artemisinin,
      in Artemisia annua L. seedlings. Compared to sucrose, a 200% increase in
      artemisinin by glucose was observed. Different ratios of fructose to glucose
      yielded artemisinin levels directly proportional to increases in relative glucose
      concentration. When the glucose analog, 3-O-methylglucose, was added with
      glucose, artemisinin production was dramatically decreased, but hexokinase
      activity was significantly increased compared to glucose alone. In contrast,
      neither mannose nor mannitol had any significant effect on artemisinin yield. In
      comparison with 30 g/l sucrose, artemisinin levels were significantly reduced by
      80% in the presence of 27 g/l sucrose + 3 g/l palatinose, which cannot be
      transported into cells through the sucrose transporter. Together these results
      suggest that both monosaccharide and disaccharide sugars are likely acting not
      only as carbon sources but also as signals to affect the downstream production of
      artemisinin, and that the mechanism of these effects appears to be complex.

PMID- 17221225
TI  - Pyramiding transgenic resistance in elite indica rice cultivars against the
      sheath blight and bacterial blight.
AB  - Elite indica rice cultivars were cotransformed with genes expressing a rice
      chitinase (chi11) and a thaumatin-like protein (tlp) conferring resistance to
      fungal pathogens and a serine-threonine kinase (Xa21) conferring bacterial blight
      resistance, through particle bombardment, with a view to pyramiding sheath blight
      and bacterial blight resistance. Molecular analyses of putative transgenic lines
      by polymerase chain reaction, Southern Blot hybridization, and Western Blotting
      revealed stable integration and expression of the transgenes in a few independent
      transgenic lines. Progeny analyses showed the stable inheritance of transgenes to
      their progeny. Coexpression of chitinase and thaumatin-like protein in the
      progenies of a transgenic Pusa Basmati1 line revealed an enhanced resistance to
      the sheath blight pathogen, Rhizoctonia solani, as compared to that in the lines
      expressing the individual genes. A transgenic Pusa Basmati1 line pyramided with
      chi11, tlp, and Xa21 showed an enhanced resistance to both sheath blight and
      bacterial blight.

PMID- 17221226
TI  - Transgenic Campanula carpatica plants with reduced ethylene sensitivity.
AB  - Fertile transgenic Campanula carpatica Jacq. plants with flowers, which had
      reduced sensitivity to ethylene were obtained by Agrobacterium tumefaciens that
      mediated transformation. The construct used for transformation contained the etr1
      1 gene from Arabidopsis thaliana under control of the flower specific fbp1
      promoter from petunia. More than 100 flowering T0 lines were tested for their
      ethylene sensitivity using 2 microl l(-1) ethylene. The tolerance level to
      ethylene varied among the lines. While control plants stopped flowering within 3
      days of exposure to ethylene, one of the transformed lines flowered for up to 27
      days. The presence and the expression pattern of the transgene in various tissues
      were studied by polymerase chain reaction (PCR) and reverse transcription (RT)
      PCR techniques. The expression of etr1-1 was significant in flowers and buds.
      Transgenic lines did not differ morphologically from control plants. The selected
      transgenic T0 lines, which were re-established from in vitro cultures showed the
      same degree of tolerance to exogenous ethylene, confirming the stability of the
      transgene in in vitro cultures. The rooting ability of the transgenic plants was
      not affected by the presence of etr1-1. T1 progeny were produced by crossing the
      transgenic line, which showed the most significant reduction in ethylene
      sensitivity with a control plant, and the analysis of the T1 plants showed 1:1
      segregation in terms of ethylene sensitivity and the presence of the transgene.

PMID- 17221227
TI  - Unique chromosome behavior and genetic control in Brassica x Orychophragmus wide
      hybrids: a review.
AB  - Researchers recognized early that chromosome behavior, as other morphological
      characters, is under genetic control and gave some cytogenetical examples such as
      the homoeologous chromosome pairing in wheat. In the intergeneric sexual hybrids
      between cultivated Brassica species and another crucifer Orychophragmus
      violaceus, the phenomenon of parental genome separation was found under genetic
      control during mitosis and meiosis. The cytogenetics of these hybrids was species
      specific for Brassica parents. The different chromosome behavior of hybrids with
      three Brassica diploids (B. rapa, B. nigra and B. oleracea) might contribute to
      the different cytology of hybrids with three tetraploids (B. napus, B. juncea and
      B. carinata). The finding that genome-specific retention or loss of chromosomes
      in hybrids of O. violaceus with B. carinata and synthetic Brassica hexaploids
      (2n=54, AABBCC) is likely related to nucleolar dominance gives new insight into
      the molecular mechanisms regarding the cytology in these hybrids. It is proposed
      that the preferential expressions of genes for centromeric proteins from one
      parent (such as the well presented centromeric histone H3) are related with
      chromosome stability in wide hybrids and nucleolar dominance is beneficial to the
      production of centromere-specific proteins of the rRNAs-donor parent and to the
      stability of its chromosomes.

PMID- 17221228
TI  - Generation of transgenic Lolium temulentum plants by Agrobacterium tumefaciens
      mediated transformation.
AB  - Lolium temulentum L. (Darnel ryegrass) has been proposed to be used as a model
      species for functional genomics studies in forage and turf grasses, because it is
      a self-fertile, diploid species with a short life cycle and is closely related to
      other grasses. Embryogenic calluses were induced from mature embryos of a double
      haploid line developed through anther culture. The calluses were broken up into
      small pieces and used for Agrobacterium tumefaciens-mediated transformation. A.
      tumefaciens strain EHA105 harboring pCAMBIA1301 and pCAMBIA1305.2 vectors were
      used to infect embryogenic callus pieces. Hygromycin was used as a selection
      agent in stable transformation experiments. Hygromycin resistant calluses were
      obtained after 4-6 weeks of selection and transgenic plants were produced in 10
      13 weeks after Agrobacterium-mediated transformation. Fertile plants were readily
      obtained after transferring the transgenics to the greenhouse. Transgenic nature
      of the regenerated plants was demonstrated by Polymerase chain reaction (PCR),
      Southern hybridization analysis, and GUS staining. Progeny analysis showed
      Mendelian inheritance of the transgenes. The transformation system provides a
      valuable tool for functionality tests of candidate genes in forage and turf
      grasses.

PMID- 17221229
TI  - Gene expression in opening and senescing petals of morning glory (Ipomoea nil)
      flowers.
AB  - We isolated several senescence-associated genes (SAGs) from the petals of morning
      glory (Ipomoea nil) flowers, with the aim of furthering our understanding of
      programmed cell death. Samples were taken from the closed bud stage to advanced
      visible senescence. Actinomycin D, an inhibitor of transcription, if given prior
      to 4 h after opening, suppressed the onset of visible senescence, which occurred
      at about 9 h after flower opening. The isolated genes all showed upregulation.
      Two cell-wall related genes were upregulated early, one encoding an extensin and
      one a caffeoyl-CoA-3-O-methyltransferase, involved in lignin production. A
      pectinacetylesterase was upregulated after flower opening and might be involved
      in cell-wall degradation. Some identified genes showed high homology with
      published SAGs possibly involved in remobilisation processes: an alcohol
      dehydrogenase and three cysteine proteases. One transcript encoded a leucine-rich
      repeat receptor protein kinase, putatively involved in signal transduction.
      Another transcript encoded a 14-3-3 protein, also a protein kinase. Two genes
      have apparently not been associated previously with senescence: the first encoded
      a putative SEC14, which is required for Golgi vesicle transport, the second was a
      putative ataxin-2, which has been related to RNA metabolism. Induction of the
      latter has been shown to result in cell death in yeast, due to defects in actin
      filament formation. The possible roles of these genes in programmed cell death
      are discussed.

PMID- 17221231
TI  - Interpreting preoperative radiographs in displaced femoral neck fractures:
      observer variability in evaluating signs of poor outcome.
AB  - OBJECTIVE: To evaluate the reproducibility of four preoperative radiographic
      signs thought to be associated with negative prognosis in dislocated femoral neck
      fractures when treated with internal fixation. SETTING: University Hospital.
      DESIGN: Standard hip radiographs of ten patients with displaced subcapital
      femoral neck fractures were studied by five orthopaedic surgeons. The radiographs
      were studied twice; the second time on average 3 months after the first reading.
      Inter- and intra-observer reliability of four radiological parameters was
      estimated. RESULTS: Poor intra- and inter-observer reproducibility of all four
      signs tested was observed. CONCLUSIONS: The decision to treat an intracapsular
      femoral neck fracture with either prosthesis or internal fixation has to be based
      on other variables than the preoperative radiographic signs evaluated in this
      study.

PMID- 17221230
TI  - Use of the AO hook-plate for treatment of unstable fractures of the distal
      clavicle.
AB  - INTRODUCTION: We used a new internal fixative implant, the AO clavicle hook
      plate, for treatment of unstable fractures of the distal clavicle. This study
      describes the operative procedure and the clinical results obtained, as well as
      discussion of the advantages and problems encountered. PATIENTS AND METHODS:
      Fifteen consecutive patients with unstable fractures of the distal clavicle (Neer
      type II) were treated using AO clavicle hook-plates. The average age of patients
      was 47 years and there were 13 males and 2 females. The mean follow-up period was
      15.5 months. Plain radiographs of clavicles were used to assess bony union.
      Functional recovery of the shoulder joint was assessed using the Constant-Murley
      scoring system. RESULTS: All fractures eventually achieved solid bony union
      within 4 months after surgery. Thirteen patients (87%) showed hook migration into
      the acromion. Clinical results were excellent with a mean Constant-Murley score
      of 89 points at final follow-up. CONCLUSION: AO clavicle hook-plates are useful
      fixative implants for unstable fractures of the distal clavicle. Static fixation
      was achieved and physiotherapy can be started immediately after surgery. Early
      removal of the implant is recommended however because hooks inserted under the
      acromion migrated into the bone in most cases.

PMID- 17221232
TI  - Characterization of a stress responsive proteinase inhibitor gene with positive
      effect in improving drought resistance in rice.
AB  - A full-length cDNA gene, designated Oryza sativa chymotrypsin inhibitor-like 1
      (OCPI1), was characterized in rice. The predicted protein of OCPI1 shows very
      high sequence identity to reported chymotrypsin inhibitors from various plant
      species. Northern-blot analysis showed that the expression of OCPI1 was strongly
      induced by dehydration stresses and abscisic acid (ABA). The expression of beta
      glucuronidase (GUS) reporter gene under the control of OCPI1 promoter transformed
      into rice was strongly induced by drought and salt stresses. Interestingly,
      strong dehydration stress-induced GUS activity was also detected in the
      transgenic rice containing the reverse sequence of OCPI1 promoter fused to GUS
      gene, suggesting of a bidirectional transcriptional activity in the OCPI1
      promoter. OCPI1 gene was over-expressed in japonica cv. Zhonghua 11 and
      transgenic plants containing single copy of transgene were tested for drought
      resistance at reproductive stage. The positive transgenic plants (OCPI1 was over
      expressed) had significantly higher grain yield and seed setting rate than the
      wild type and the negative transgenic control (no over-expression of the
      transgene) under the severe drought stress conditions, whereas the potential
      yield of transgenic plants under normal growth conditions was not affected.
      Chymotrypsin-inhibitor activity assay showed that the crude protein of the
      positive transgenic plants had stronger inhibitory activity than the negative
      control. Transgenic plants had less decrease of total proteins than the wild type
      under drought stress. Taken together, these data indicate that OCPI1 might
      potentially be useful in the genetic improvement of drought resistance in rice.

PMID- 17221233
TI  - Arbuscular mycorrhizas and ectomycorrhizas of Uapaca bojeri L. (Euphorbiaceae):
      sporophore diversity, patterns of root colonization, and effects on seedling
      growth and soil microbial catabolic diversity.
AB  - The main objectives of this study were (1) to describe the diversity of
      mycorrhizal fungal communities associated with Uapaca bojeri, an endemic
      Euphorbiaceae of Madagascar, and (2) to determine the potential benefits of
      inoculation with mycorrhizal fungi [ectomycorrhizal and/or arbuscular mycorrhizal
      (AM) fungi] on the growth of this tree species and on the functional diversity of
      soil microflora. Ninety-four sporophores were collected from three survey sites.
      They were identified as belonging to the ectomycorrhizal genera Afroboletus,
      Amanita, Boletus, Cantharellus, Lactarius, Leccinum, Rubinoboletus, Scleroderma,
      Tricholoma, and Xerocomus. Russula was the most frequent ectomycorrhizal genus
      recorded under U. bojeri. AM structures (vesicles and hyphae) were detected from
      the roots in all surveyed sites. In addition, this study showed that this tree
      species is highly dependent on both types of mycorrhiza, and controlled
      ectomycorrhization of this Uapaca species strongly influences soil microbial
      catabolic diversity. These results showed that the complex symbiotic status of U.
      bojeri could be managed to optimize its development in degraded areas. The use of
      selected mycorrhizal fungi such the Scleroderma Sc1 isolate in nursery conditions
      could be of great interest as (1) this fungal strain is very competitive against
      native symbiotic microflora, and (2) the fungal inoculation improves the
      catabolic potentialities of the soil microflora.

PMID- 17221234
TI  - Translational regulation of neuronal electrical properties.
AB  - The nervous system has an in-built capability to adjust its responsiveness to
      excitation according to the history of electrical activity faced by the neurons
      embedded within its networks. This control over excitability represents a form of
      homeostasis and is exhibited at multiple stages in the flow of information from
      the genome to the expression and modification of protein products. Information on
      the nature of the homeostatic phenomenon at some of these stages is still limited
      and emerging. This article outlines the various stages at which such neuronal
      intrinsic plasticity has been observed and draws particular attention to the role
      of the translation repressor protein, Pumilio, as an important factor in the
      process. The study of this protein is providing insights into the regulation of
      neuronal excitability and offers an important research target with benefits to
      investigators in many areas of neuroscience.

PMID- 17221236
TI  - Liquid chromatography-tandem mass spectrometry of bioactive pharmaceutical
      compounds in the aquatic environment--a decade's activities.
AB  - The occurrence of bioactive pharmaceutical compounds in the aquatic environment
      is an emerging concern. Liquid chromatography, coupled with mass spectrometry (LC
      MS) or tandem mass spectrometry (LC-MS-MS) using an electrospray ionization
      interface, is a crucial tool for addressing this issue. We review in this
      manuscript LC-MS and LC-MS-MS studies on waterborne PhACs in the last decade,
      including research activity in different geographical areas and the current
      status of the technology used for sample preparation, chromatographic separation,
      and mass spectrometric detection. A detailed overview on quality-control and
      quality-assurance (QC/QA) procedures is also presented, with emphasis on the need
      for a concerted approach to determine the numerical values associated with
      detection limits, and the use of low-level data qualifiers.

PMID- 17221235
TI  - Evaluation of two proteomics technologies used to screen the membrane proteomes
      of wild-type Corynebacterium glutamicum and an L-lysine-producing strain.
AB  - The membrane proteomes of a wild-type Corynebacterium glutamicum and an L-lysine
      producing strain were quantitatively analyzed by two complementary proteomics
      techniques -- anion exchange chromatography AIEC/SDS-PAGE and 16BAC-PAGE/SDS-PAGE
      -- and the results were compared. Although both techniques allow for the fast
      screening of differences in protein abundance, AIEC/SDS-PAGE was superior to
      16BAC-PAGE/SDS-PAGE with respect to protein separation, it was more suitable for
      relative protein quantification, and allowed more differentially regulated
      proteins to be detected (the succinate dehydrogenase complex, an ABC-type
      cobalamin/Fe(3+) siderophore transport system, the maltose binding protein, and a
      subunit of the cytochrome bc-aa(3) supercomplex were upregulated, while a
      periplasmic component of an ABC-type transporter and an iron-regulated ABC-type
      transporter were downregulated in the producer). The results indicate the
      important role of tricarboxylic acid cycle enzymes as well as the adaptation of
      transport processes in L-lysine-producing cells. Since the only genetic
      differences between the wild type and the L-lysine producer occur between four
      central metabolic enzymes in the cytoplasm, our study illustrates the complex
      effects of metabolic engineering on cell physiology and the power of the new
      AIEC/SDS-PAGE proteomics approach to detect these effects.

PMID- 17221237
TI  - Preparation of Fe3O4-C18 nano-magnetic composite materials and their cleanup
      properties for organophosphorous pesticides.
AB  - Magnetic Fe3O4-C18 composite nanoparticles of approximately 5-10 nm in size were
      synthesized and characterized by IR spectroscopy, atomic absorption spectroscopy,
      X-ray diffraction, and transmission electron microscopy. The magnetic Fe3O4-C18
      composite nanoparticles were applied for cleanup and enrichment of
      organophosphorous pesticides. Comparative studies were carried out between
      magnetic Fe3O4-C18 composite nanoparticles and common C18 materials. Residues of
      organophosphorous pesticides were determined by gas chromatography in combination
      with a nitrogen/phosphorus detector. The cleanup and enrichment properties of
      magnetic Fe3O4-C18 composite nanoparticles are comparable with those of common
      C18 materials for enrichment of organophosphorous pesticides, but the cleanup and
      enrichment are faster and easier to perform.

PMID- 17221238
TI  - Hydride generation activity of arsenosugars and thioarsenicals.
AB  - The major arsenosugar compounds have been reported to be hydride-generation
      active, however to a lesser extent in comparison with the inorganic arsenicals.
      We report here for the first time the identity and quantity of the volatile
      arsenicals generated by As-sugar-SO(3), As-sugar-SO(4), dimethylarsinoyl acetic
      acid and dimethylarsinoyl ethanol. Only one major volatile compound was
      identified for all four compounds studied: dimethylarsine. This means that the As
      C bond to the longer carbon chain was cleaved during the hydride-generation
      process. Theoretical calculations at the RHF/6-31G(d,p) ab initio level confirm
      that this As-C bond is much weaker than the As-CH(3) bonds. Furthermore, it was
      revealed that the sulphur analogue of dimethylarsinic acid (DMAS ) is hydride
      generation-active at pH 7 in contrast to dimethylarsinic acid, despite the fact
      that arsenic is also pentavalent. This has been substantiated by the calculation
      of the change in susceptibility of the arsenic towards nucleophilic attack when
      oxygen is replaced by sulphur. Hence, DMAS can easily be mistaken for a trivalent
      arsenic species.

PMID- 17221239
TI  - Amperometric biosensor for the determination of creatine.
AB  - An amperometric biosensor for the determination of creatine was developed. The
      carbon rod electrode surface was coated with sarcosine oxidase (SOX) and creatine
      amidinohydrolase by cross-linking under glutaraldehyde vapour. The SOX from
      Arthrobacter sp. 1-1 N was purified and previously used for creation of a
      creatine biosensor. The natural SOX electron acceptor, oxygen, was replaced by an
      [Fe(CN)(6)](3-) /[ Fe(CN)(6)](4-) redox mediating system, which allowed
      amperometric detection of an analytical signal at +400-mV potential. The response
      time of the biosensor was less than 1 min. The biosensor showed a linear
      dependence of the signal vs. creatine concentration at physiological creatine
      concentration levels. The optimal pH in 0.1 M tris(hydroxymethyl)aminomethane
      (Tris)-HCl buffer was found to be at pH 8.0. The half-life of the biosensor was 8
      days in 0.1 M Tris-HCl buffer (pH 8.0) at 20 degrees C. Principal scheme of
      consecutively followed catalytic reactions used to design a biosensor for the
      determination of creatine.

PMID- 17221240
TI  - Comparison of different extraction methods for the determination of essential
      oils and related compounds from aromatic plants and optimization of solid-phase
      microextraction/gas chromatography.
AB  - Different extraction methods for the subsequent gas chromatographic determination
      of the composition of essential oils and related compounds from marjoram
      (Origanum majorana L.), caraway (Carum carvi L.), sage (Salvia officinalis L.),
      and thyme (Thymus vulgaris L.) have been compared. The comparison was also
      discussed with regard to transformation processes of genuine compounds,
      particularly in terms of expenditure of time. Hydrodistillation is the method of
      choice for the determination of the essential oil content of plants. For
      investigating the composition of genuine essential oils and related, aroma-active
      compounds, hydrodistillation is not very useful, because of discrimination and
      transformation processes due to high temperatures and acidic conditions. With
      cold solvent extraction, accelerated solvent extraction, and supercritical fluid
      extraction, discrimination of high and non-volatile aroma-active components as
      well as transformation processes can be diminished, but non-aroma-active fats,
      waxes, or pigments are often extracted, too. As solid-phase microextraction is a
      solvent-free fully automizable sample preparation technique, this was the most
      sparing to sensitive components and the most time-saving method for the rapid
      determination of the aroma compounds composition in marjoram, caraway, sage, and
      thyme. Finally, solid-phase microextraction could be successfully optimized for
      the extraction of the aroma components from the plants for their subsequent gas
      chromatographic determination.

PMID- 17221241
TI  - [Anti-interleukin-5 therapy for eosinophilic diseases].
AB  - In a number of diseases with eosinophilia, elevated interleukin (IL)-5 levels are
      detected in the peripheral blood and/or tissues. IL-5 plays an important role in
      regulating the production, differentiation, recruitment, activation, and survival
      of eosinophils. Therefore, neutralizing IL-5 by blocking antibodies seems a
      promising approach in the treatment of eosinophilic diseases. Clinical trials
      have demonstrated that anti-IL-5 therapy results in a rapid decrease in
      peripheral blood eosinophil numbers. Moreover, improvement of symptoms in
      patients with lymphocytic variants of hypereosinophilic syndromes, in
      eosinophilic esophagitis and chronic rhinitis with nasal polyposis has been
      observed. In contrast, in patients with bronchial asthma or atopic eczema, anti
      IL-5 therapy showed only moderate or no clinical effects. Future studies will
      have to identify those eosinophilic diseases in which anti-IL-5 antibodies are
      effective, perhaps with the help of newly developed biomarkers.

PMID- 17221242
TI  - [Radiological imaging of the upper gastrointestinal tract. Part II. The stomach].
AB  - CT, and multi-detector row computed tomography in particular, play a very
      important role in staging malignant tumors of the stomach. The optimized
      technique of so called "Hydro-CT", including distension to the gastric wall with
      1-1.5 l oral contrast media, mainly water, has fostered the diagnostic value of
      CT in the diagnosis of diseases of the stomach. By using the "Hydro-CT"
      technique, the detection rate for gastric carcinoma is now between 89% and 94%,
      and for liver metastasis between 85% and 92%. For overall T staging, the
      sensitivity is rather low at between 43% and 65%, and for the lymph nodes between
      64 and 88%. Depending on tumor type, multislice computed tomography (MSCT)
      supplies morphological details for defining the type of lesion (polyps,
      gastritis, lymphoma, gastrointestinal stromal tumours, carcinoma). Nevertheless,
      a definite differential diagnosis remains difficult. In addition, multiplanar
      reconstruction (MPR), derived from multi-detector row computed tomography data
      sets, is very helpful in localizing these pathologies and demonstrating their
      anatomic relationship to adjacent organs and vascular structures. MRI plays no
      major part in the diagnostic evaluation of the upper GI-tract.

PMID- 17221244
TI  - [Nephropexy in the course of time. Aspects of an historical surgical technique].
AB  - The first successful nephropexy was performed in the year 1881. From this time,
      surgical therapy of nephroptosis has always been a subject of discussion. A
      partly uncritical acceptance led to nephropexy being the most performed
      urological operation at the beginning of the 20th century, with up to 200
      different surgical variations. As early as the 15th century, a first description
      of ren mobilis was made by Alessius de Pedemontanus. The first surgical
      intervention for the treatment of nephroptosis was performed by Gilmore in 1870.
      In 1877, the American Dowell from New Orleans tried a fixation of the kidney
      through a seton, however, this operation failed. Eventually in 1881, Eugen Hahn
      from Berlin was able to perform the first successful nephropexy, he named this
      method "nephroraphy". In 1882, the first modification was made by Bassini with
      sutures through the renal capsule. Finally, the gynaecologist George Edebohl led
      nephropexy into a great popularity and secured the method through numerous
      technical innovations. By 1936, approximately 170 different surgical methods
      existed for fixation of the kidney. An accurate diagnosis is imperative before
      performing nephropexy. There were times in which this operation was carried out
      much too often and, therefore, had a bad reputation. However, it is not correct
      to drop nephropexy altogether as some would prefer. The statement by Professor
      Voelcker from Halle in the year 1911 that for all those who have a urinary
      obstruction and those with a beginning dilation, nephropexy is still justified
      and may - when correctly performed provide many blessings". Nothing needs to be
      added to this.

PMID- 17221243
TI  - [Macrophage specific MRI imaging for antigen induced arthritides. A potential new
      strategy for the diagnosis of rheumatoid arthritis].
AB  - PURPOSE: The present work describes the potential of iron oxides for the
      detection of macrophages in synovitis in experimental, antigen-induced arthritis.
      METHODS: The pivotal role of macrophages in rheumatoid arthritis (RA) in humans
      and in antigen-induced arthritis (AIA) in animal models is discussed. The latter
      appear to be very similar in many aspects to the human RA. We show the potential
      for iron oxide-enhanced magnetic resonance imaging (MRI) to determine the
      macrophage content in the arthritic synovial membranes. The results of our own
      research, as well as those of other research groups, are presented and discussed.
      RESULTS: MRI after the intravenous (i.v.) administration of iron oxides enables
      the depiction of macrophage content in arthritic synovial membranes in AIA
      through the effects of the intracellular compartmentalisation of iron oxide
      particles. These effects can be demonstrated in 24-h delayed images after i.v.
      contrast application, on T2-weighted spin-echo or turbo-spin-echo sequences, and
      especially on T2*-weighted gradient-echo sequences. The signal effects are not
      only apparent in high field strength (4.7 Tesla) but also on 1.5 Tesla clinical
      scanners. CONCLUSIONS AND PERSPECTIVES: The use of iron oxides enables the
      determination of the macrophage content in synovitis in animals with AIA. This
      parameter represents a potential marker to determine disease activity, and
      possibly represents a marker to evaluate the effectiveness of specific therapies
      in human RA. Current knowledge of iron oxide-enhanced MRI is limited to animal
      models. The clinical evaluation of this new method in patients with RA has not
      yet been performed. However, based on the considerations presented here,
      significant progress in the diagnostic work-up of RA can be expected.

PMID- 17221245
TI  - [Extracorporeal shock-wave lithotripsy induced ultrastructural changes to the
      renal parenchyma under aspirin use. Electron microscopic findings in the rat
      kidney].
AB  - BACKGROUND: The risk of hemorrhagic complications after extracorporeal shock-wave
      lithotripsy (ESWL) increases in patients with aspirin intake, but the hematoma
      inducing mechanism has not been understood completely at the ultrastructural
      level. METHODS: The effect off shock-waves on the kidneys of male Wistar-rats
      (n=24) was investigated in an experimental setting using a special ESWL device.
      Ultrastructural examination was performed by light-, transmission electron- and
      scanning electron microscopy. RESULTS: Shock-wave induced tissue damage appeared
      in all kidneys independently of aspirin intake. Endothelial detachment, lethal
      cell injury, gaps and mechanical disruption of the glomerular basement membrane
      were regularly found. After 1 week, repair processes were completed with evidence
      of permanent fibrosis in some cases. CONCLUSIONS: ESWL can induce modest as well
      as fatal damage to renal tissue cells. Therefore, after an ESWL-induced hematoma
      a second ESWL should not be performed within 1 week of the first treatment.

PMID- 17221246
TI  - [Renal arteriovenous fistula].
AB  - Arteriovenous malformations are important but uncommon differential diagnoses for
      space occupying renal lesions with unknown genesis. In the following case report,
      a 41-year-old patient complained about continuing right flank pain. Computer
      tomography indicated a possible renal cell carcinoma and the patient was admitted
      to our clinic. Further diagnostics, including contrast medium-enhanced bolus CT,
      colour coded duplex sonography, renovasography and MR-angiography, revealed a
      large arteriovenous fistula of the entire right kidney. Because of the size and
      aneurysmatic appearance of this fistula, we performed a nephrectomy. Since this
      operation the patient has been free of complaints.

PMID- 17221247
TI  - [Does cigarette smoking influence the survival of patients with prostate
      cancer?].
AB  - In the last few years, prostate cancer has become one of the most common causes
      of mortality worldwide. It is therefore important to detect possible risk factors
      for this malignant disease. Besides risk factors which increase incidence,
      attention should be paid to factors which have a possible influence on the course
      of the disease. In our analysis, we demonstrate a worse course for the disease in
      patients with prostate cancer who smoked cigarettes at the time of first
      diagnosis. In spite of comparable staging, grading and PSA values at the time of
      primary diagnosis, individuals who smoked had a threefold higher risk of dying
      from prostate cancer. This effect is probably caused by metabolic changes which
      are activated by cigarette smoking and promote tumor growth and the development
      of metastases.

PMID- 17221248
TI  - [Pelvic kidney in childhood. Specific features, concomitant pathologies and
      useful diagnostic investigations].
AB  - In a retrospective analysis we studied the case histories of 31 children who had
      been seen in our department for investigation of pelvic ectopic kidney between
      January 1994 and June 2005. The evaluation of each involved the medical history,
      ultrasound examination, VCUG, and DMSA scan or MAG3 diuresis renogram. Of the 31
      children, 21 (67.7%) had initially been referred to our department for further
      investigation and clarification because renal agenesis was suspected. In the
      remaining 10 (32.3%) children the pelvic kidney was an incidental finding
      observed during investigation of various other conditions. Overall, 7 (22.6%) of
      the 31 were symptomatic (recurrent urinary tract infections, abdominal pain,
      hypertension, hydronephrosis), while 77.4% (24/31) were completely free of
      symptoms at the time of follow-up. Ultrasound revealed that the ectopic kidney
      was on the left in 64.5% (20/31) of these cases. Nuclear scans performed both at
      the time of the initial diagnosis and at follow-up were available for 11 of the
      31 children and showed a mild improvement of the partial function of the pelvic
      kidney, from a mean of 25.6% to a mean of 34.6%. In conclusion, whenever renal
      agenesis is suspected on ultrasonographic examination, the investigator should
      first consider renal ectopia; ultrasound examination with the bladder full is the
      definitive diagnostic procedure. For asymptomatic cases we recommend regular
      ultrasound monitoring of the kidney -- at first every 6 months and later once a
      year. In cases with complex anatomy MRI is a suitable method for further
      diagnostic work-up.

PMID- 17221249
TI  - [The treatment of periprosthetic infections].
AB  - Periprosthetic infections are severe complications following total joint
      arthroplasty. The infection rate is estimated to be 0.5-2%. Systemic diseases
      such as rheumatoid arthritis and previous surgery are considered risk factors for
      infection. The infection rate in the present patient cohort was low (0.72%). The
      recurrence rate (23.4%) is due to patients with rheumatoid arthritis and septic
      total knee arthroplasties. Successful treatment is dependent on various factors,
      one of which involves accurate preoperative bacterial diagnostics. Joint fluid
      aspiration is the appropriate procedure. Open biopsy or arthroscopically guided
      biopsy can be performed in cases of unclear diagnostic results. Early infection
      can be treated with thorough joint debridement without exchanging fixed implant
      components; "low-grade" or late infections require revision with implant removal
      in a one or two stage septic revision according to clearly determined algorithms.
      Antibiotic therapy is mandatory, and a combination with rifampicin is a very
      useful basis.

PMID- 17221251
TI  - [Tendon ruptures in rheumatic patients].
AB  - In the course of rheumatoid arthritis, changes to tendons occur in different
      areas. This can lead to rupture if not prevented at an early stage. In
      particular, regions with extreme joint thickness, high mechanical wear and tear
      and narrow regions present a higher risk of synovitis. This primarily affects the
      tendons of the hand, where the extensor digitorum minimus tendon and the extensor
      and flexor pollicis tendons are most at risk. There is a high possibility of
      rotator cuff lesion in the shoulder area during the course of a secondary
      synovitis dependent raised shoulder, or by bursitis or tendonitis. A rupture of
      the biceps tendon is also increased by omarthritis or synovitis in the sulcus.
      For the foot, the posterior tibial tendon is most commonly effected, which if
      primarily or secondarily damaged can lead to a rheumatic flat foot. In addition,
      there can be partial or complete destruction in the Achilles tendon area, which
      is definitely pathognomonic. The narrow syndrome in the flexor hallucis and the
      extensor digitorum tendons are less common.

PMID- 17221252
TI  - [Revision of the recommendations of the Commission on Pharmacotherapy of the
      German Society for Rheumatology. Recommendations for supportive therapy for
      Sjogren's syndrome].
AB  - For the treatment of sicca symptoms as a manifestation of Sjogren's syndrome
      there are various tear substitutes as well as artificial saliva. The appropriate
      substances are discussed in this article. In addition to reducing symptoms, some
      of the effective compounds offer the advantage of infection prophylaxis in the
      form of better lubrication of the mucous membranes in the airways as well as
      reduced susceptibility to candidiasis. The presence of bromhexin in the catalogue
      of the statutory medical insurance agencies is recommended. Certain of the
      available drugs are still only available in foreign pharmacies.

PMID- 17221253
TI  - [Revision of the recommendations of the Commission on Pharmacotherapy of the
      German society for Rheumatology. Therapy with tumour necrosis factor blockers for
      inflammatory rheumatic illnesses].
AB  - Inflammatory rheumatic illnesses are associated with various types of pain as
      well as handicaps. The so called basic therapies are not sufficiently effective
      in many patients or are terminated due to side effects. This is where tumor
      necrosis factor blockers (TNF) can be used. In many cases, they lead to a
      substantial improvement of the symptoms, a reduction in disease related
      laboratory parameters, improvement in quality of life to stopping disease related
      damage when their effect is rapid. Common and severe side effects are few,
      although long-term data are still limited. The following contribution lists
      recommendations for the indications and symptomatology for the use of TNF
      blockers.

PMID- 17221254
TI  - Do terrestrial invertebrates experience floodplains as landscape mosaics?
      Immediate and longer-term effects of flooding on ant assemblages in a floodplain
      forest.
AB  - Considering the floodplain landscape as a mosaic of habitat patches at different
      successional stages is useful for understanding (1) the processes associated with
      individual floods and (2) the legacy of flood history. Here, we investigate the
      applicability of the mosaic model to opportunistic ant species inhabiting the
      floodplain. Ground-active ant assemblages in river red gum (Eucalyptus
      camaldulensis) floodplain forest in south-eastern Australia were sampled before
      and for two years after a major flood in 2000-2001 at 24 sites with different
      inundation histories. Despite the mobility and opportunistic life history traits
      of floodplain ants, flood history appeared to impose a persistent mosaic
      structure on ant assemblages. Increasing duration of inundation of the forest
      floor was associated with decreasing species richness. beta-diversity was low,
      with the ant species at the most inundation-prone sites being a subset of those
      at drier sites. Less extensive flooding occurred in 2002-2003, enabling the
      consistency of short-term responses to inundation to be assessed. Flooding acts
      as a resetting mechanism, creating a characteristic ant assemblage. After
      floodwaters receded, there was little evidence of convergence in the structure of
      ant assemblages through time between sites flooded for different durations. The
      persistence of dissimilarities in ant assemblages suggests that succession
      towards terrestrialization was either not occurring or that it was operating at a
      rate that was too slow to be detected.

PMID- 17221255
TI  - Investment in defense and cost of predator-induced defense along a resource
      gradient.
AB  - An organism's investment in different traits to reduce predation is determined by
      the fitness benefit of the defense relative to the fitness costs associated with
      the allocation of time and resources to the defense. Inherent tradeoffs in time
      and resource allocation should result in differential investment in defense along
      a resource gradient, but competing models predict different patterns of
      investment. There are currently insufficient empirical data on changes in
      investment in defensive traits or their costs along resource gradients to
      differentiate between the competing allocation models. In this study, I exposed
      tadpoles to caged predators along a resource gradient in order to estimate
      investment in defense and costs of defense by assessing predator-induced
      plasticity. Induced defenses included increased tail depth, reduced feeding, and
      reduced swimming activity; costs associated with these defenses were reduced
      developmental rate, reduced growth, and reduced survival. At low resource
      availability, these costs predominately resulted in reduced survival, while at
      high resource availability the costs yielded a reduced developmental rate.
      Defensive traits responded strongly to predation risk, but did not respond to
      resource availability (with the exception of feeding activity), whereas traits
      construed as costs of defenses showed the opposite pattern. Therefore, defensive
      traits were highly sensitive to predation risk, while traits construed as costs
      of defense were highly sensitive to resource allocation tradeoffs. This
      difference in sensitivity between the two groups of traits may explain why the
      correlation between the expression of defensive traits and the expression of the
      associated defense costs was weak. Furthermore, my results indicate that genetic
      linkages and mechanistic integration of multiple defensive traits and their
      associated costs may constrain time and resource allocation in ways that are not
      addressed in existing models.

PMID- 17221256
TI  - Density-dependent outcomes in a digestive mutualism between carnivorous Roridula
      plants and their associated hemipterans.
AB  - Recent studies have shown that mutualisms often have variable outcomes in space
      and time. In particular, the outcomes may be dependent on the density of the
      partners with unimodal or saturating outcomes providing stability to the
      mutualism. We examine density-dependent outcomes of an obligate, species-specific
      mutualism between a South African carnivorous plant (Roridula dentata) and a
      hemipteran (Pameridea) that facilitates prey digestion, but also sucks plant sap.
      Plants occur in sandy, leached, nitrogen-poor soils and have no digestive enzymes
      to digest prey. Instead they rely on obligately dependent hemipterans to supply
      nitrogen by digesting prey for them and defecating on their leaves. We documented
      the densities of Pameridea on Roridula in the field. In the greenhouse, we
      manipulated the hemipteran densities on Roridula and measured the mean relative
      growth rates of plants with differing hemipteran densities. Plants exhibited a
      unimodal response to the density of their mutualist partners. Those with no
      hemipterans had negative growth rates, suggesting that hemipterans are important
      in facilitating nitrogen absorption. Plants with intermediate hemipteran
      densities had positive growth rates but growth rates were negative under very
      high hemipteran densities. Our research provides support for variable and
      unimodal outcomes in mutualism. Unimodal outcomes may be particularly important
      in obligate mutualisms and this is one of the few studied outside of pollinating
      seed parasite mutualisms. In this system, extrinsic factors such as other
      predators may affect the mutualism by altering the numbers of hemipterans.

PMID- 17221257
TI  - A new intelligent distension system for hollow organs.
AB  - Controlled distension of hollow organs is an accepted technique for generating
      reproducible visceral stimuli. We have constructed a new, flexible and
      intelligent distension system in which discomfort, pain and autonomic responses
      are recorded online. These responses can be fed back into the system in a
      regulatory loop and be used to shape the distension paradigm. Consequently, it is
      possible to take all subjects to a state of equal, although subjective, level of
      discomfort or pain, even though pressure, tension and volume might be totally
      different. By using a variable airflow, this new distension system can be
      effectively used in all kinds of paradigms, e.g. phasic, tonic, or ramp
      distensions or customized combinations of them. The system can be used to control
      pressure, volume or tension. A refinement of the system is that it is possible to
      automatically change the controlled entity during a distension, e.g. from an
      isobaric ramp directly into an isovolumetric tonic phase. Furthermore, the
      distension device allows double distensions with independent distension
      paradigms.

PMID- 17221258
TI  - A matching pursuit-based signal complexity measure for the analysis of newborn
      EEG.
AB  - This paper presents a new relative measure of signal complexity, referred to here
      as relative structural complexity (RSC), which is based on the matching pursuit
      (MP) decomposition. By relative, we refer to the fact that this new measure is
      highly dependent on the decomposition dictionary used by MP. The structural part
      of the definition points to the fact that this new measure is related to the
      structure, or composition, of the signal under analysis. After a formal
      definition, the proposed RSC measure is used in the analysis of newborn
      electroencephalogram (EEG). To do this, firstly, a time-frequency decomposition
      dictionary is specifically designed to compactly represent the newborn EEG
      seizure state using MP. We then show, through the analysis of synthetic and real
      newborn EEG data, that the relative structural complexity measure can indicate
      changes in EEG structure as it transitions between the two EEG states; namely
      seizure and background (non-seizure).

PMID- 17221259
TI  - Wine grape (Vitis vinifera L.) color associates with allelic variation in the
      domestication gene VvmybA1.
AB  - During the process of crop domestication and early selection, numerous changes
      occur in the genetic and physiological make-up of crop plants. In grapevine
      (Vitis vinifera) numerous changes have occurred as a result of human selection,
      including the emergence of hermaphroditism and greatly increased variation in
      berry color. This report examines the effect of human selection on variable skin
      color by examining the variation present in the gene VvmybA1, a transcriptional
      regulator of anthocyanin biosynthesis. In over 200 accessions of V. vinifera, the
      insertion of the retroelement Gret1 in the promoter region of VvmybA1 was in
      strong association with the white-fruited phenotype. This retroelement was
      inserted at the same location for each individual in which it was present.
      Additional polymorphisms in the VvmybA1 gene were also strongly associated with
      red or pink fruited accessions, including variation that was generated by the
      excision of Gret1 from the promoter of VvmybA1. Differences in nucleotide
      diversity were observed between the white and pigmented alleles of VvmybA1,
      suggesting that the white allele arose only once or a limited number of times.
      Rarely, association of Gret1 with the white fruited phenotype was not observed,
      suggesting that the white phenotype can also be obtained through mutation in
      additional genes. These results provide evidence that variation in one
      transcriptional regulator has generated an allelic series strongly associated
      with fruit color variation in cultivated grapevine. These findings provide
      information about the evolution of grapes since domestication and have direct
      implications for the regulation of fruit and wine quality of this important crop
      plant.

PMID- 17221260
TI  - Effect of high-intensity interval training and detraining on extra VO2 and on the
      VO2 slow component.
AB  - To examine the effect of 6-week of high-intensity interval training (HIT) and of
      6-week of detraining on the VO2/Work Rate (WR) relationship and on the slow
      component of VO2, nine young male adults performed on cycle ergometer, before,
      after training and after detraining, an incremental exercise (IE), and a 6-min
      constant work rate exercise (CWRE) above the first ventilatory threshold (VT1).
      For each IE, the slope and the intercept of the VO2/WR relationship were
      calculated with linear regression using data before VT1. The difference between
      VO2max measured and VO2max expected using the pre-VT1 slope was calculated (extra
      VO2). The difference between VO2 at 6th min and VO2 at 3rd min during CWRE
      (DeltaVO2(6'-3')) was also determined. HIT induced significant improvement of
      most of the aerobic fitness parameters while most of these parameters returned to
      their pre-training level after detraining. Extra VO2 during IE was reduced after
      training (130 +/- 100 vs. -29 +/- 175 ml min(-1), P = 0.04) and was not altered
      after detraining compared to post-training. DeltaVO2(6'-3') during CWRE was
      unchanged by training and by detraining. We found a significant correlation (r2 =
      0.575, P = 0.02) between extra VO2 and DeltaVO2(6'-3') before training. These
      results show that an alteration of extra VO2 can occur without any change in the
      VO2 slow component, suggesting a possible dissociation of the two phenomena.
      Moreover, the fact that extra VO2 did not change after detraining could indicate
      that this improvement may remain after the loss of other adaptations.

PMID- 17221261
TI  - [Hip surgery immediately following stent revascularization of an acute myocardial
      infarction].
AB  - Due to the high risk of perioperative adverse events, elective surgery should be
      suspended for at least 4 weeks after myocardial infarction and coronary stent
      revascularization, as current guidelines suggest. This report describes the
      successful management of a patient who underwent urgent surgery for a displaced
      hip fracture immediately after stent revascularization of an acute myocardial
      infarction. No new perioperative ischemia was detected. The therapeutic options
      and the timing of surgical procedures after stent revascularization are
      discussed.

PMID- 17221262
TI  - Acetabular revisions using a cementless oblong cup: five to ten year results.
AB  - The purpose of this paper was to evaluate the results of acetabular revisions
      with the use of an oblong revision cup that is designed with its longitudinal
      diameter elongated relative to its transverse diameter. Between 1996 and 2001, 62
      hips in 60 patients underwent an acetabular revision with the insertion of a LOR
      acetabular component. Seven hips were lost to follow-up or the patients died; the
      remaining 55 hips (53 patients) remained in follow-up for an average of 7.2 years
      (range: 5.0-10.1 years). One socket was revised for aseptic loosening, and
      another was operated on for a late polyethylene liner dissociation. The average
      Harris hip score (HHS) improved from 34 to 79. Results were rated as excellent in
      16 hips, good in 28, fair in six and poor in three. Radiographic analysis
      demonstrated an improvement in the average vertical displacement of the hip
      centre: 49 hips had a well-fixed, bone-ingrown cup and four had a stable fibrous
      union. For large superolateral acetabular bone deficiencies, this implant
      facilitated a complex reconstruction without the need for bulk structural
      acetabular bone grafts, provided good clinical results and showed satisfactory
      stability at the midterm follow-up.

PMID- 17221263
TI  - Escape flight initiation in the fly.
AB  - Visually evoked escape flight initiation in Drosophila, according to the accepted
      account, involves a rapid extension of the middle legs that propels the fly into
      the air while the wings are still folded. This description has remained
      unchallenged and is accounted for in terms of the activation of a simple neural
      circuit, the Giant fibre (GF) system. The accepted description of escape is
      however inconsistent with the sequence of events recorded when the GF system is
      stimulated. Specifically, previous electrophysiological recordings have shown
      that the wing depressor muscles are activated before the wings are in a position
      to be depressed because they have not yet been elevated. Here we show that the
      accepted behavioural description is wrong. Escape flight initiation actually
      begins with wing elevation. The current model of the GF system is revised to
      account for the actual sequence of events that occur when a fly escapes.

PMID- 17221264
TI  - Direct cerebral oxygenation monitoring--a systematic review of recent
      publications.
AB  - This review has been compiled to assess publications related to the clinical
      application of direct cerebral tissue oxygenation (PtiO2) monitoring published in
      international, peer-reviewed scientific journals. Its goal was to extract
      relevant, i.e. positive and negative information on indications, clinical
      application, safety issues and impact on clinical situations as well as treatment
      strategies in neurosurgery, neurosurgical anaesthesiology, neurosurgical
      intensive care, neurology and related specialties. For completeness' sake it also
      presents some related basic science research. PtiO2 monitoring technology is a
      safe and valuable cerebral monitoring device in neurocritical care. Although a
      randomized outcome study is not available its clinical utility has repeatedly
      been clearly confirmed because it adds a monitoring parameter, independent from
      established cerebral monitoring devices. It offers new insights into cerebral
      physiology and pathophysiology. Pathologic values have been established in peer
      reviewed research, which are not only relevant to outcome but are treatable. The
      benefits clearly outweigh the risks, which remains unchallenged in all
      publications retrieved. It is particularly attractive because it offers
      continuous, real-time data and is available at the bedside.

PMID- 17221266
TI  - Intraoperative management to prevent cerebrospinal fluid leakage after
      microvascular decompression: dural closure with a "plugging muscle" method.
AB  - Our objective is to present surgical techniques used for the prevention of
      cerebrospinal fluid leakage after microvascular decompression (MVD). From January
      1996 to February 2006, microvascular decompression for hemifacial spasm or
      trigeminal neuralgia was performed in 678 consecutive patients. In order to
      achieve watertight dural closure, several pieces of muscle were interposed
      between the dura when the dura was sutured; the dura was stitched with the
      addition of muscle pieces to plug the dural defect. In cases where the mastoid
      air cell system was opened, bone wax was used to seal the opened surface of the
      cavity, and a muscle patch was applied for the secondary sealing. The
      cranioplasty was performed using polymethylmethacrylate (PMMA) bone cement. Only
      2 (0.29%) of 678 patients, who underwent MVD followed by dural closure using
      several muscle pieces to plug the potential dural defect, suffered from CSF
      leaks. Both were treated with lumbar subarachnoid drainage; neither patient
      required a lumbar peritoneal shunt or a revision operation. A watertight dural
      closure with the addition of muscle pieces in a "plugging" fashion, along with
      sealing the opened surface of the mastoid cavity using bone wax and cranioplasty
      using bone cement, provides a simple and effective technique for the prevention
      of CSF leakage after MVD.

PMID- 17221265
TI  - Combined motor and somatosensory evoked potentials for intraoperative monitoring:
      intra- and postoperative data in a series of 69 operations.
AB  - The primary objective of neurophysiologic monitoring during surgery is to avoid
      permanent neurological injury resulting from surgical manipulation. To prevent
      motor deficits, either somatosensory (SSEP) or transcranial motor evoked
      potentials (MEP) are applied. This prospective study was conducted to evaluate if
      the combined use of SSEP and MEP might be beneficial. Combined SSEP/MEP
      monitoring was attempted in 100 consecutive procedures, including intracranial
      and spinal operations. Repetitive transcranial electric motor cortex stimulation
      was used to elicit MEP from muscles of the upper and lower limb. Stimulation of
      the tibial and median nerves was performed to record SSEP. Critical SSEP/MEP
      changes were defined as decreases in amplitude of more than 50% or increases in
      latency of more than 10% of baseline values. The operation was paused or the
      surgical strategy was modified in every case of SSEP/MEP changes. Combined
      SSEP/MEP monitoring was possible in 69 out of 100 operations. In 49 of the 69
      operations (71%), SSEP/ MEP were stable, and the patients remained neurologically
      intact. Critical SSEP/ MEP changes were seen in six operations. Critical MEP
      changes with stable SSEP occurred in 12 operations. Overall, critical MEP changes
      were recorded in 18 operations (26%). In 12 of the 18 operations, MEP recovered
      to some extent after modification of the surgical strategy, and the patients
      either showed no (n = 10) or only a transient motor deficit (n = 2). In the
      remaining six operations, MEP did not recover and the patients either had a
      transient (n = 3) or a permanent (n = 3) motor deficit. Critical SSEP changes
      with stable MEP were observed in two operations; both patients did not show a new
      motor deficit. Our data again confirm that MEP monitoring is superior to SSEP
      monitoring in detecting impending impairment of the functional integrity of
      cerebral and spinal cord motor pathways during surgery. Detection of MEP changes
      and adjustment of the surgical strategy might allow to prevent irreversible
      pyramidal tract damage. Stable SSEP/MEP recordings reassure the surgeon that
      motor function is still intact and surgery can be continued safely. The combined
      SSEP/ MEP monitoring becomes advantageous, if one modality is not recordable.

PMID- 17221267
TI  - Gas-related impact of pneumoperitoneum on systemic wound healing.
AB  - INTRODUCTION: The aim of the present study was to investigate the gas-dependent
      effects of pneumoperitoneum on wound healing distant from the abdomen. MATERIALS
      AND METHODS: Dorsal skin incisions were performed in 54 male Sprague-Dawley rats.
      A CO(2) or a helium pneumoperitoneum of 3 mmHg was maintained before, with an
      overall duration of 30 min (each n = 18). Rats in the control group received
      laparotomy only (n = 18). Animals were killed after 5 and 10 days. The
      infiltration of macrophages (CD 68), expression of matrix metalloproteinase 13
      (MMP-13) and collagen I/III ratios were analysed in the dorsal skin wounds.
      RESULTS: Both after 5 and 10 days, infiltration of macrophages and expression of
      MMP-13 were greatest after helium pneumoperitoneum. After 5 days, collagen I/III
      ratio was significantly increased in the helium group. After 10 days, collagen
      I/III ratio was lowest in the CO(2) group. CONCLUSION: Our results suggest
      beneficial effects on systemic wound healing for helium pneumoperitoneum as
      compared to CO(2).

PMID- 17221270
TI  - Complete pancreatic encasement of the portal vein--surgical implications of an
      extremely rare anomaly.
AB  - BACKGROUND: Due to the complex embryologic development, pancreatic anatomy can be
      very variable. DISCUSSION: The authors present the second ever reported case in
      the literature of a complete pancreatic encasement of the portal vein which
      forced us to alter the standard operative procedure of pancreatic head resection,
      thus enabling possible dangerous complications.

PMID- 17221269
TI  - Surgery for cystic lymphangioma in Gorlin-Goltz syndrome.
AB  - INTRODUCTION: We present a case of three major lymphomesenteric cysts in a female
      patient with known basal cell nevus syndrome (BCNS or Gorlin-Goltz syndrome).
      DISCUSSION: Although those cysts have been reported to appear in this syndrome,
      the exact prevalence is not known. In this case, the patient suffered from severe
      and recurrent abdominal pain due to bowel obstruction. CONCLUSION: By causing
      severe symptoms, cystic lymphangiomas are an important complication of the BCNS
      despite of their seldom occurrence. Surgeons confronted with intraabdominal
      masses in a patient with BCNS should always be aware of this manifestation of the
      disorder and plan interdisciplinary operations.

PMID- 17221268
TI  - Specific topics and complications of parenteral nutrition.
AB  - BACKGROUND/AIMS: Total parenteral nutrition (TPN) has proven a tremendous advance
      in all disciplines in medicine but itself introduces a spectrum of possible
      complications related to both the parenteral nutritional solution as well as the
      technique of intravenous delivery. Our aim is to review the specific
      complications of TPN. MATERIALS AND METHODS: This article presents a critical
      literature review of relevant topics in TPN-related complications-metabolic,
      infections, and nutrition related. RESULTS: Special emphasis focuses on
      complications of TPN arising from thrombosis or infectious sequelae related to
      the central venous catheterization and metabolic complications involving the
      kidneys, bones, liver, and biliary tract. CONCLUSIONS: Awareness and surveillance
      of TPN-related complications can prevent, potentially, some of these
      complications related to parenteral nutritional support.

PMID- 17221271
TI  - Functional improvement in spinal cord injury-induced neurogenic bladder by
      bladder augmentation using bladder acellular matrix graft in the rat.
AB  - Spinal cord injury (SCI) rostral to the lumbosacral level causes bladder
      hyperreflexia and detrusor-sphincter dyssynergia (DSD), which are accompanied by
      bladder hypertrophy. We hypothesize that bladder augmentation using a bladder
      acellular matrix graft (BAMG) can improve the function of SCI-mediated neurogenic
      bladder. In female rats (n = 35), SCI was induced by transection of the spinal
      cord at the lower thoracic level. Eight weeks following spinalization, bladder
      augmentation using BAMG was performed after hemicystectomy of the hypertrophic
      bladder. Cystometrography was performed at 8 weeks after spinalization and again
      at 8 weeks after augmentation. Several urodynamic parameters were measured and
      the grafted bladder was histologically evaluated. Thirty one rats were alive 8
      weeks after spinalization. Twenty two (71%) rats developed hyperreflexic bladders
      and nine (29%) rats had underactive bladders before bladder augmentation. Twenty
      six rats survived until 8 weeks after augmentation. Urodynamic parameters showed
      improvement in some bladder functions in both hyperreflexic and underactive
      bladders after augmentation. In addition, bladder compliance was increased in
      hyperreflexic bladders and decreased in underactive bladders. Bladder
      augmentation decreased bladder capacity in high-capacity rats and increased it in
      low-capacity rats. Histological evaluation showed complete regeneration of BAMG
      in SCI-induced neurogenic bladder at 8 weeks after augmentation. This is the
      first report suggesting that the voiding function in SCI-induced neurogenic
      bladder can be improved by augmentation using BAMG. Improved voiding function was
      accompanied by histological regeneration of BAMG.

PMID- 17221272
TI  - Risk reduction of subdural collections following endoscopic third
      ventriculostomy.
AB  - OBJECT: To evaluate the efficacy and safety using fibrin glue and absorbable
      hemostats for packing the endoscopic tract in a pediatric population in the
      prevention of subdural fluid collections after endoscopic third ventriculostomy.
      MATERIALS AND METHODS: Twenty-one endoscopic third ventriculostomies were
      performed in 20 hydrocephalic children with a mean age of 22 months over a 4-year
      period using uniformly this technique. Six children, with age ranged 6 days to 22
      months (mean 9 months), had severe ventriculomegaly with thin brain mantle less
      than 10 mm. There was no mortality and no permanent morbidity related to the
      endoscopic procedure. One child developed an asymptomatic collection, which could
      be managed conservatively and was most likely attributed to the young age of the
      child and the assumed poor cerebrospinal fluid absorption ability. Lost
      compliance of the brain parenchyma may play an additional role, which was not
      related to the thickness of the brain mantle. No adverse effects regarding the
      material used for sealing were observed over a mean follow-up of 23 months.
      CONCLUSIONS: Subdural fluid collections could be prevented in 20 out of 21
      procedures by using this technique regardless of the thickness of the brain
      mantle, the application of mixture of fibrin glue and hemostatic agents seems to
      be safe, and we consider this technique effective in reducing the risk of this
      potential complication.

PMID- 17221273
TI  - Lhermitte-Duclos disease.
AB  - BACKGROUND: Lhermitte-Duclos disease (LDD; dysplastic gangliocytoma of the
      cerebellum) is a rare hamartoma of the cerebellum. It was first described by
      Lhermitte and Duclos in 1920 as "Sur un ganglioneurome diffus du cortex du
      cervelet" (Lhermitte and Duclos [Bull Assoc Fr Etude Cancer 9:99-107, 1920]).
      Since then, due to its rarity and the variability of its presentation, the
      diagnosis is often missed. It is not only important for the neurosurgeon and the
      pathologist to be aware of this entity so as to differentiate from malignant
      lesions but also to distinguish it from other cerebellar malformations, which may
      be hypoplastic or dysplastic, focal or diffuse in nature, with brain stem and
      cerebral involvement, and varied natural course. ILLUSTRATIVE CASE: We report a
      case of LDD in a 16-year-old boy. This case exemplifies the rarity of the disease
      leading to lack of awareness with which the diagnosis was easily missed. We also
      take this opportunity to discuss the clinical presentation, neuroradiological
      appearance, and a brief summary of histopathological findings, pathogenetic
      considerations, and neurogenetical aspects.

PMID- 17221275
TI  - Daytime polysomnography for early diagnosis and treatment of patients with
      suspected sleep-disordered breathing.
AB  - Excessive daytime sleepiness (EDS) is a common complaint among patients with
      sleep-disordered breathing (SDB). Population-based studies on traffic and
      industrial accidents suggest a relationship between EDS and life-threatening
      events, and adults with EDS have cognitive and memory problems. Nocturnal
      polysomnography (nPSG) is essential for diagnosing SDB but it is time and energy
      consuming. We examined the usefulness of daytime polysomnography (dPSG) for the
      early diagnosis and treatment of patients with suspected SDB. We studied 108
      consecutive patients aged 51.9 +/- 13.5 years (mean+/-SD). All patients underwent
      dPSG and nPSG. The number of apnea/hypopnea episodes per hour (apnea/hypopnea
      index: AHI) and the number of 3% desaturation episodes per hour (desaturation
      index: DSI) were calculated. All patients were classified into two groups. The
      REM group consisted of subjects who had an AHI < or = 25/h, AHI(REM)/AHI(NREM) >
      2, and AHI(NREM) < 15/h. Those who did not satisfy these criteria were placed in
      the NREM group. Continuous positive airway pressure (CPAP) titration was
      performed for patients whose AHI was > or =20/h on dPSG. Using the international
      classification of sleep disorders, 96 patients were diagnosed as obstructive
      sleep apnea [including five upper airway resistance syndrome (UARS) patients],
      six patients were snoring, four had idiopathic hypersomnia due to a medical
      condition, and two had circadian rhythm sleep disorders. The sensitivity of dPSG
      for AHI was 81.0%, specificity was 100%, and accuracy was 83.5%. The sensitivity
      and accuracy of dPSG for AHI in the REM group were considerably lower than in the
      NREM group. There was no significant difference for optimal CPAP between dPSG and
      nPSG. In the five patients with UARS, their AHI, DSI, and arousal index on dPSG
      were 0.92 +/- 1.2/h, 2.9 +/- 3.4/h, and 29.3 +/- 3.5/h, respectively, and their
      AHI and DSI on nPSG were 3.2 +/- 2.5/h and 2.8 +/- 2.4/h, respectively. However,
      their respiratory effort-related arousals were 37.9 +/- 7.4/h, and their arousal
      index was 33.2 +/- 6.3/h. The five patients with UARS were also treated with
      CPAP, and their daytime sleepiness was improved. Although dPSG has limitations,
      these results indicate that dPSG recording is clinically useful for the diagnosis
      of and determination of types of treatment in patients with suspected SDB.

PMID- 17221274
TI  - Association of physical activity with sleep-disordered breathing.
AB  - This study was performed to determine whether there is a protective association
      between participation in vigorous or vigorous/moderately vigorous physical
      activity and the prevalence of sleep-disordered breathing (SDB). Polysomnographic
      and questionnaire data from the baseline examination of 4,275 participants in the
      Sleep Heart Health Study (SHHS) were analyzed in relation to information on
      amount of physical activity and other potentially relevant factors collected from
      five SHHS parent cohorts (Atherosclerosis Risk in Communities Study,
      Cardiovascular Health Study, Framingham Heart Study, Strong Heart Study, and
      Tucson Epidemiologic Study of Airways Obstructive Diseases). Logistic regression
      models were fitted to determine if amount and strenuousness of physical activity
      was associated with the presence of SDB. At least 3 h per week of vigorous
      physical activity reduced the odds of SDB, defined as a respiratory disturbance
      index (RDI) of at least 15 apneas/hypopneas per hour (Adjusted OR, 0.68; 95%CI,
      0.51-0.91). A qualitatively similar but slightly weaker association was observed
      when SDB was defined as a RDI > or = 10 per hour (Adjusted OR, 0.81; 95%CI, 0.64
      1.02). These findings remained after adjustment for sleepiness and restricting
      analyses to participants with good health. Three or more hours of moderately
      vigorous or vigorous physical activity also appeared to confer some protection
      against SDB, but these associations were weaker. Gender- and obesity-stratified
      analyses suggested that the protective association between physical activity and
      SDB occurred primarily in men and those who were obese. A program of regular
      vigorous physical activity of at least 3 h per week may be a useful adjunctive
      treatment modality for SDB, but this association needs confirmation with a
      prospective clinical trial.

PMID- 17221276
TI  - Demographic characteristics of 3,659 Japanese patients with obstructive sleep
      apnea-hypopnea syndrome diagnosed by full polysomnography: associations with
      apnea-hypopnea index.
AB  - Information on obstructive sleep apnea-hypopnea syndrome (OSAHS) in Japan has
      been limited. The purposes of this clinical study were to evaluate the
      demographic characteristics of Japanese OSAHS patients and to assess how
      demographic factors are associated with OSAHS severity. We analyzed 3,659 OSAHS
      patients who underwent polysomnographic evaluation between January 2000 and
      December 2004 at 11 hospitals in Niigata Prefecture, Japan. Data consisted of
      apnea-hypopnea index (AHI) and demographic characteristics, including sex, age,
      and body-mass index, for statistical analysis. Levels of obesity were classified
      according to the WHO criteria. The male-to-female patient ratio for OSAHS was
      4.6, and male patients presented more severe OSAHS than female patients. High AHI
      and a high proportion of moderate to serious OSAHS (AHI > or = 15) were found
      among the patients in their 30s, as well as female patients in their 70s and male
      patients in their 80s. The AHI and the proportion of moderate-to-serious OSAHS
      (AHI > or = 15) were greater in patients classified as underweight than in normal
      weight patients. In conclusion, there is a higher male predominance in the
      prevalence of OSAHS, and in both sexes, the results suggest different
      pathophysiological mechanisms of deteriorating OSAHS between adults under age 55
      and adults 55 years or over. In addition, underweight patients exhibit more
      severe OSAHS than normal weight patients.

PMID- 17221277
TI  - Histological changes and apoptosis of cartilage layer in human anterior cruciate
      ligament tibial insertion after rupture.
AB  - The purpose of this study is to investigate the histological changes and
      apoptosis of cartilaginous layers in human anterior cruciate ligament (ACL)
      tibial insertion at different time periods after rupture. By using a core reamer,
      35 tibial insertions of ruptured ACLs were obtained during primary ACL
      reconstructions (number of days after injury: 19-206 days). A histological
      examination was performed and a terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining assay was
      carried out to detect apoptosis. The average thickness of the cartilage layer,
      the glycosaminoglycan-stained area and the number of chondrocytes per millimeter
      decreased with time. The percentage average of TUNEL-positive chondrocytes was
      42.0 +/- 16.2. The histological degenerative changes of the cartilage layer in
      the ruptured ACL tibial insertion progressed with time, especially in the first 2
      months. Moreover, chondrocyte apoptosis continued from 19 to 206 days after
      rupture. The results may help elucidate the etiology of the histological changes
      of the insertion, and may help in devising optimal treatment protocols for ACL
      injuries if apoptosis is controlled. Moreover, we consider that using a surviving
      ligament and minimizing a debridement of ACL remnant during ACL reconstruction
      may be important for ACL reconstruction to maintain cartilage layers in ACL
      insertions.

PMID- 17221278
TI  - Hibernoma: a case report demonstrating usefulness of MR angiography in
      characterizing the tumor.
AB  - Hibernoma is a rare, benign soft-tissue tumor composed of brown fat. In the past,
      there has been an extensive discussion of the CT attenuation and MRI signal
      characteristics of hibernomas. However, recent reports have focused upon the
      tumor vascularity of hibernomas. We describe the only case in the literature
      which utilizes state of the art contrast enhanced MR angiography to clearly
      characterize the surface and intratumoral vessels to help confirm the diagnosis
      of a hibernoma and aid in the preoperative planning.

PMID- 17221281
TI  - A trypsin inhibitor from Cassia obtusifolia seeds: isolation, characterization
      and activity against Pieris rapae.
AB  - A trypsin inhibitor was isolated from Cassia obtusifolia by ammonium sulfate
      precipitation, Sepharose 4B-trypsin affinity and Sephadex G-75 chromatography.
      The inhibitor consisted of a single polypeptide chain with a molecular mass of
      19, 812.55 Da. It was stable from pH 2 to 12 for 24 h, whereas it was unstable
      either above 70 degrees C for 10 min or under reduced conditions. The inhibitor,
      which inhibited trypsin activity with an apparent Ki of 0.3 microM, had one
      reactive site involving a lysine residue. The native inhibitor was resistant to
      pepsin digestion, whereas the heated inhibitor produced 40% degree of
      susceptibility. The disulfide linkage and lysine residue were important in
      maintaining its conformation. Partial amino acid sequence of the purified protein
      showed a high degree of homology with various members of the Kunitz inhibitor
      family. Moreover, the inhibitor showed significant inhibitory activity against
      trypsin-like proteases present in the larval midgut on Pieris rapae and could
      suppress the growth of larvae.

PMID- 17221282
TI  - Continuous ambulatory peritoneal dialysis in patients with renal failure due to
      multiple myeloma.
AB  - Continuous ambulatory peritoneal dialysis (CAPD) is being used only in limited
      number of patients with renal failure due to multiple myeloma, despite having
      better preservation of hemoglobin, higher clearance of paraproteins, and higher
      chances of recovery of renal function than maintenance hemodialysis. We are
      reporting our short-term experience of five patients with multiple myeloma who
      presented with renal failure and required long term continuous ambulatory
      peritoneal dialysis for the treatment of uremia.

PMID- 17221283
TI  - Tubularized incised plate urethroplasty for hypospadias reoperations in 100
      patients.
AB  - OBJECTIVES: To determine the key points for a successful redo hypospadias
      procedure using tubularized incised plate urethroplasty operation. METHODS: A
      retrospective chart review of a cohort of 100 patients (Mean age: 4.5 years,
      range: 2-12) who had undergone a redo tubularized incised plate urethroplasty
      operation was performed. Fischer exact and Chi square tests were used for
      statistical analysis. RESULTS: The incidence of complications of tubularized
      incised plate urethroplasty reoperation after failed repairs of meatal
      advancement and glanuloplasty procedure (n: 14), meatal based flap (n: 36), and
      tubularized incised plate urethroplasty (n: 50) were 29% (n: 4), 22% (n: 8) and,
      28% (n: 14) respectively (P > 0.05). The overall complication rate was 26% (n:
      26). Eighteen patients (18%) had fistula, five had meatal stenosis (5%), two had
      dehiscence (2%) and one had neourethral stenosis (1%). Postoperatively, fistula
      was closed in 18 patients and 5 underwent meatoplasty. Two patients with
      dehiscence and one with neourethral stenosis underwent an unsuccessful third redo
      tubularized incised plate urethroplasty reoperation and they were candidates for
      a complex hypospadias repair (3%). The ultimate success rate of tubularized
      incised plate urethroplasty reoperation after treatment of complications was 97%.
      CONCLUSION: Tubularized incised plate urethroplasty is a safe and efficacious
      alternative procedure for hypospadias reoperations if the urethral plate has no
      scars and outcome is favourable if the first failed hypospadias repair is a
      meatal based flap procedure. The complication rate increases if the urethral
      plate has been previously incised in the midline and a redo third redo must be
      avoided.

PMID- 17221284
TI  - A male patient with right-sided thoracic kidney, diabetes mellitus, hearing loss
      and renal dysfunction.
AB  - A 48-year-old man with diabetes mellitus and hypertension was found to have a
      thoracic right-sided ectopic kidney with a sensorineuronal hearing loss and
      tubular abnormalities such as hyponatremia, hypokalemia, metabolic alkalosis with
      microalbuminuria. He was treated with ACEI and sodium and potassium supplements.
      However, this only partially corrected his metabolic abnormalities.

PMID- 17221285
TI  - Incidence and risk factors of coronary heart disease in elderly patients on
      chronic hemodialysis.
AB  - AIM: To determine the incidence of coronary heart disease (CHD) in patients (pts)
      over 65 years (y) and its relation to common risk factors. METHODS: We
      retrospectively studied 128 hemodialysis (HD) pts (80 M and 48 F), mean age 73+/
      6.5 years, mean time on HD 44.4+/-26.4 months and BMI 25.4+/-3 kg/m2. They were
      evaluated for: age, sex, smoking, diabetes, hypertension, left ventricular
      hypertrophy, secondary hyperparathyroidism (SHP), inflammation, as evidence by
      elevated level of hsCRP, hyperhomocysteinemia (HOC), time on HD, fluid overload
      and adequacy of HD. Forty-eight pts (37%) had CAD diagnosed by coronary
      angiography in 22 (46%) and (201)TL-chloride dipyridamole stress test in 26
      (54%). RESULTS: There was a statistically significant correlation between CAD and
      increasing age (p<0.0001). The relative risk was significantly increased
      concerning: (1) male over female pts (RR: 1.95, p<0.01), (2) diabetic vs. non
      diabetic pts (RR: 2.09, p<0.001), (3) patients with SHP over pts with iPTH
      values<250 pg/ml (RR: 2.16, p<0.001), (4) hypertensive vs. non hypertensive pts
      (RR: 2.26, p=0.002), (5) smokers vs. non smokers (RR: 1.69, p<0.05), (6) pts with
      HOC over pts with normal homocysteine values (RR: 2.09, p<0.05), (7) pts with
      increased CRP levels over pts with normal CRP levels (RR: 1.8, p<0.01), (8) pts
      undergoing HD for 36 vs. 12 months (RR: 1.71, p=0.03), (9) between pts with
      inadequate or adequate HD (RR: 1.73, p=0.02). No significant correlation existed
      between CAD incidence and the other risk factors. CONCLUSIONS: Coronary heart
      disease incidence in elderly HD patients increases with age, male sex, diabetes,
      SHP, hypertension, increased CRP levels, HOC, smoking, time on HD and inadequacy
      of HD.

PMID- 17221286
TI  - Heme oxygenase 1 expression in rat liver during ageing and ethanol intoxication.
AB  - Heme oxygenase 1 (HO-1) expression is recognized as a marker of cellular response
      to oxidative stress; since ageing is believed to be related to oxidative "wear
      and tear", HO-1 may represent a candidate biomarker of ageing. In our study, the
      hepatic expression of HO-1 mRNA, evaluated by RT-PCR in 2.5-24 month-old rats,
      was higher at 6 months than at 2.5 months of age, but thereafter increased no
      further: on the contrary, a declining trend was observed. However, while 2.5
      month-old rats responded to acute ethanol intoxication by displaying increased
      expression of liver HO-1 mRNA, and 6 month-old rats exhibited a mild response, 18
      month-old rats did not show any response; this phenomenon suggests that during
      development and ageing the transcriptional response to oxidative stress
      decreases. In our view, the finding that HO-1 expression did not increase
      progressively during ageing may be explained by a decreased transcriptional
      ability to respond to stress in older animals, rather than by a reduction in
      oxidative stress.

PMID- 17221287
TI  - Identification of the RA response element and transcriptional silencer in human
      alphaCaMKII promoter.
AB  - The promoter of alpha subunit of the rat calcium/calmodulin-dependent protein
      kinase II (alphaCaMKII) gene was identified to contain an essential TATA element.
      Cell-based functional assay showed that the rat promoter displayed greater
      activity in neuronal cells than in non-neuronal cells. To characterize the human
      alphaCaMKII promoter, we have developed a promoter-reporter gene assay using
      different cell lines. A 2047 base pairs (bp) human alphaCaMKII gene promoter was
      cloned from human genomic DNA. Unlike the rat alphaCaMKII promoter, DNA sequence
      analysis showed that the human promoter was devoid of TATA element. We made
      series deletions of the promoter and fused the different sizes of the human
      promoter sequences to a luciferase reporter gene. The promoter-reporter
      constructs were transfected into human neuroblastoma SH-SY5Y, human neuroblastoma
      BE(2)-M17, and rat pheochromocytoma PC12 neuronal cell lines as well as human
      embryonic kidney HEK293 and human glioma U251 non-neuronal cell lines. The
      reporter gene assay demonstrated that the human alphaCaMKII promoter displayed
      high activity in the neuronal cell lines, while the activity was low in non
      neuronal cell lines. All-trans retinoic acid (RA) enhanced the promoter activity
      in SH-SY5Y cells. Further analysis showed that there were two RA response
      elements located between +11 and +136 and -1911 to -593. In addition, we have
      identified a potent silencer at position -179 to -244 of the human alphaCaMKII
      promoter.

PMID- 17221288
TI  - Use of biosynthetic fractional 13C-labeling for backbone NMR assignment of
      proteins.
AB  - We describe a simple approach to classify amino acid residue types in NMR spectra
      of proteins for supporting the backbone resonance assignments. It makes use of
      the differences in biosynthetic pathways of the 20 amino acids in Escherichia
      coli. Therefore, it is distinct from the parameters routinely exploited in the
      backbone resonance assignment such as chemical shifts and spin topology
      information. The combination of biosynthetically directed fractional 13C-labeling
      and uniform 15N-labeling enables us to obtain both residue-type specific
      information and sequential connectivities from a single protein sample. The
      residue-type classification exploiting biosynthetic pathways can be used for
      accelerating the conventional backbone assignment procedure.

PMID- 17221289
TI  - Coordinative organization of lingual propulsion during the normal adult swallow.
AB  - Lingual propulsion during swallowing is characterized by the sequential elevation
      of the anterior, middle, and dorsal regions of the tongue. Although lingual
      discoordination underlies many swallowing disorders, the coordinative
      organization of lingual propulsion during the typical and disordered swallow is
      poorly understood. The purpose of this investigation was to quantitatively
      describe the coordinative organization of lingual propulsion during the normal
      adult swallow. Tongue movement data were obtained from the X-Ray Microbeam
      Database at the University of Wisconsin. Movement of four pellets placed on
      specific tongue regions were tracked in 36 healthy adult participants while they
      swallowed 10 cc of water across five discrete trials. The propulsive action of
      the tongue during bolus transport was quantified using a cross-correlation
      analysis. Lingual transit time (LTT), which was defined as the interval (lag
      time) between the movements of the anterior- and posterior-most tongue regions,
      was determined to be approximately 168 ms. The average time interval (lag)
      between the movements of the posterior tongue regions was significantly shorter
      than the intervals between more anterior tongue regions. The results also suggest
      that during bolus transport movement patterns of the anterior tongue regions are
      distinct from those of the posterior tongue regions. Future work is needed to
      determine if the absence of the observed coordinative organization of lingual
      propulsion is indicative of oral stage dysphagia.

PMID- 17221290
TI  - Assessment of swallowing by oropharyngoesophageal scintigraphy in patients with
      amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron
      disease in adults, and dysphagia is one of its most frequent and disabling
      symptoms. Oropharyngoesophageal scintigraphy (OPES) permits a functional and
      semiquantitative study of the various stages of swallowing. We studied 28 ALS
      patients (12 females and 16 males; mean age = 63.57 +/- 10.39 yr SD), who were
      clinically rated against the ALSFRS scale (Amyotrophic Lateral Sclerosis
      Functioning Rating Scale) and underwent OPES with (99m)Tc-nanocolloid using
      either a liquid or a semisolid bolus. The semiquantitative parameters we analyzed
      were Oral Transit Time (OTT), Pharyngeal Transit Time (PTT), Esophageal Transit
      Time (ETT), Retention Index (RI), and Esophageal Emptying Rate (EER(10s)). Hence,
      the OPES performed with a semisolid bolus produced a higher proportion of
      pathologic values for the swallowing variables than when liquid bolus was used.
      Analyzed by grouping the patients into classes according to their bulbar ALSFRS
      scores, we found a significant increase in the OTT (p < 0.005), PTT (p < 0.02),
      and Oropharyngeal Retention Index (OPRI) (p < 0.0004) variables in ALS patients
      with more severe bulbar involvement. OPES has turned out to be a very important
      examination for detecting tracheal-bronchial inhalation and it also offers the
      possibility of acquiring a semiquantitative evaluation of the amount of food
      inhaled. In our experience, OPES in patients with ALS has been easy to use,
      economic, well tolerated, and capable of supplying precise indications with
      regard to the extent of the swallowing disorder, which permits a better clinical
      definition of the ALS patient.

PMID- 17221292
TI  - The first year of human life: coordinating respiration and nutritive swallowing.
AB  - This study provides the first documented report of the maturation of breathing
      swallowing coordination during feeding in ten healthy term human infants through
      the first year of life. A total of 15,073 swallows were obtained across ten
      assessments between 48 h and 12 months of age. Midexpiratory swallows represented
      the dominant pattern of breathing-swallowing coordination within the first 48 h
      (mean = 45.4%), but the prevalence of this pattern declined rapidly in the first
      week to 29.1% (p = 0.012). Inspiratory-expiratory swallows increased with age (p
      < 0.001), particularly between 9 (37.0%) and 12 months (50.4%). Between 72.6% and
      75.0% of swallows were followed by expiration in the latter 6 months, which is an
      adult-like characteristic. These data suggest that while postswallow expiration
      is a robust feature of breathing-swallowing coordination from birth, two major
      shifts in the precise patterns occur: the first after 1 week of postnatal feeding
      experience and the second between 6 and 12 months, most likely due to neural and
      anatomical maturation.

PMID- 17221294
TI  - Could a policy of provision of hip protectors to elderly nursing home residents
      result in cost savings in acute hip fracture care? The case of Ontario, Canada.
AB  - Hip fractures are an important problem in nursing homes. Hip protectors are
      external devices that decrease the risk of hip fracture in elderly nursing home
      residents. We estimated the overall healthcare cost savings from a hypothetical
      strategy of provision of hip protectors to elderly nursing home residents in
      Ontario, Canada. In a recent meta-analysis, we determined that a strategy of
      provision of hip protectors decreases the risk of hip fracture in nursing home
      residents. INTRODUCTION: Our objective was to determine whether the provision of
      hip protectors to all Ontario nursing home residents aged > or =65 years could
      result in cost savings, stemming from reductions in initial hospitalizations for
      hip fracture. METHODS: We conducted a cost analysis from a Ministry of Health
      perspective (one year cycle length). The efficacy of the intervention was
      estimated from a meta-analysis of randomized controlled trials. RESULTS: A
      strategy of provision of hip protectors to all 60,775 elderly Ontario nursing
      home residents could result in an overall mean cost savings of 6.0 million
      Canadian dollars in one year (95% credibility interval, -26.4 million, 39.7
      million), with a probability of cost savings of 0.63 (assuming no additional
      labor costs). In sensitivity analyses, decreasing hip protector price increased
      cost savings, whereas additional labor expenditures for application for hip
      protectors decreased cost savings. CONCLUSION: In conclusion, if hip protectors
      can be provided to elderly Ontario nursing home residents without additional
      labor expenditures, there is a reasonable probability that such a strategy may
      result in healthcare cost savings.

PMID- 17221295
TI  - Hospitalised osteoporotic vertebral fractures in Spain: analysis of the national
      hospital discharge registry.
AB  - This population-based study reveals clinical and epidemiologic characteristics of
      hospitalised osteoporosis-related vertebral fractures and indicates an
      association with a substantial hospital burden in Spain. These data provide a
      basis for assessing the impact of these fractures on the Spanish health-care
      system and to estimate future care requirements. INTRODUCTION: Vertebral
      fractures (VF) are recognised as the most frequent complication of osteoporosis.
      Our objective was to determine the clinico-epidemiological characteristics and
      health-care burden of hospitalised VF in Spain. METHOD: From the 2002 National
      Hospital Discharge Register, records for all osteoporosis-related VF in the
      Spanish population aged >or=30 years and over were retrieved. Diagnostic
      categories included the ICD-9-CM codes 805 and 733.xx. Population data were drawn
      from the National Statistics Institute. RESULTS: In total, 7,100 records were
      eligible for analysis. According to Deyo-adapted Charlson index, 62% of cases had
      no associated comorbidity. VF were the cause of hospitalisation in 52% of cases.
      Overall in-hospital mortality was 3.5%. Men had higher adjusted mortality than
      women. Mean hospital stay was 11.4+/-0.2 days. Identified cases amounted to a
      hospitalisation rate of 2.76 cases per 10,000 population aged >or=30 years.
      Direct inpatient hospital costs exceeded 41 million euros and accounted for
      0.078% of Spanish expenditure on hospitalisations and specialised care in 2002.
      CONCLUSIONS: The national discharge database reveals epidemiological features of
      hospitalised osteoporosis-attributable VF and indicates an association with a
      substantial hospital burden in Spain. Our data provide a basis for assessing the
      impact of these fractures on the Spanish health-care system and to estimate
      future care requirements.

PMID- 17221298
TI  - DNA fingerprinting and phylogenetic analysis of WNIN rat strain and its obese
      mutants using microsatellite markers.
AB  - Wistar is the oldest rat strain to be introduced in biomedical research, and
      various stocks of this strain are maintained in laboratories across the globe.
      The Wistar strain maintained in our facilities is 85 years old and is not typed
      genetically so far. Recently, two obese mutant rat strains evolved from this
      stock, one with euglycemia and the other with impaired glucose tolerance. These
      mutant rat strains, along with the parental Wistar stock and two other rat
      strains maintained in our facilities (WKY and F-344), were subjected to PCR-based
      DNA fingerprinting using microsatellite markers to evolve molecular signatures
      unique to them. Of the 96 markers screened, we identified a marker, leukosianin,
      that shows polymorphism between the strains tested and thus appears to be quite
      useful for rat strain identification. Also, the microsatellite data generated
      were subjected to hierarchical cluster analysis to generate a dendrogram and to
      estimate the phylogenetic closeness and distance between the rat strains tested.
      It was observed that the Wistar strain and its mutants maintained in our facility
      are genetically distinct and phylogenetically separate from the other two
      standard strains WKY and F-344.

PMID- 17221296
TI  - Risk of mortality during four years after substance detoxification in urban
      adults.
AB  - The objective of this analysis was to assess the mortality rate and risk factors
      in adults, with substance dependence, who are not receiving primary medical care
      (PC). Date and cause of death were identified using the National Death Index data
      and death certificates for 470 adults without PC over a period of almost 4 years
      after detailed clinical assessment after detoxification. Factors associated with
      risk of mortality were determined using stepwise Cox proportional hazards models.
      Subjects were 76% male, 47% homeless, and 47% with chronic medical illness; 40%
      reported alcohol, 27% heroin, and 33% cocaine as substance of choice. Median age
      was 35. During a period of up to 4 years, 27 (6%) subjects died. Median age at
      death was 39. Causes included: poisoning by any substance (40.9% of deaths),
      trauma (13%), cardiovascular disease (13.6%), and exposure to cold (9.1%). The
      age adjusted mortality rate was 4.4 times that of the general population in the
      same city. Among these individuals without PC in a detoxification unit, risk
      factors associated with death were the following: drug of choice [heroin: hazard
      ratio (HR) 6.9 (95% confidence interval (CI) 1.6-31.1]; alcohol: HR 3.7 (95% CI
      0.79-16.9) compared to cocaine); past suicide attempt (HR 2.1, 95% CI 0.96-4.5);
      persistent homelessness (HR 2.4, 95% CI 1.1-5.3); and history of any chronic
      medical illness (HR 2.1, 95% CI 0.93-4.7). Receipt of primary care was not
      significantly associated with death (HR 0.85, 95% CI 0.34-2.1). Risk of mortality
      is high in patients with addictions and risk factors identifiable when these
      patients seek help from the health care system (i.e., for detoxification) may
      help identify those at highest risk for whom interventions could be targeted.

PMID- 17221297
TI  - Dexamethasone damages the rat stomach but not small intestine during inhibition
      of COX-1.
AB  - We previously reported that inhibition of both COX-1 and COX-2 is required for
      the gastrointestinal ulcerogenic properties of nonsteroidal anti-inflammatory
      drugs (NSAIDs). Inhibition of COX-1 up-regulates COX-2 expression, and the
      prostaglandins (PGs) produced by COX-2 help to maintain the mucosal integrity
      during inhibition of COX-1. In the present study we investigated whether
      dexamethasone damages rat gastrointestinal mucosa during inhibition of COX-1 and
      further developed the idea that COX-2 expression is a key event in the
      ulcerogenic actions of NSAIDs. Dexamethasone was given p.o. in the absence or
      presence of SC-560 (a selective COX-1 inhibitor), and the stomach or intestine
      was examined 8 or 24 hr later, respectively. Neither dexamethasone nor SC-560
      alone damaged the gastrointestinal mucosa. In the presence of SC-560, however,
      dexamethasone damaged the stomach but not small intestine. SC-560 decreased
      PGE(2) levels in both tissues, with a gradual recovery accompanying the up
      regulation of COX-2 expression, and both the recovery of PGE(2) levels and the
      expression of COX-2 were inhibited by dexamethasone. In the animals treated with
      SC-560, iNOS expression was up-regulated in the intestinal but not the gastric
      mucosa, and this response was also inhibited by dexamethasone. These results
      suggest a risk from steroid therapy in the stomach when COX-2 expression is up
      regulated. Dexamethasone does not provoke damage in the intestine, despite
      inhibiting the up-regulation of COX-2 expression under conditions of PG
      deficiency; at least one of the reasons is that this agent prevents the
      expression of iNOS, a major factor in the pathogenesis of intestinal lesions.

PMID- 17221300
TI  - Phylogenetic analysis of AA-genome Oryza species (Poaceae) based on chloroplast,
      mitochondrial, and nuclear DNA sequences.
AB  - Species in the genus Oryza (Poaceae) contain 10 genomic types and are distributed
      in pan-tropics of the world. To explore phylogenetic relationships of Oryza
      species having the AA-genome, DNA sequences of the chloroplast trnL intron and
      trnL-trnF spacer, mitochondrial nad1 intron 2, and nuclear internal transcribed
      spacer were analyzed, based on materials from 6 cultivated (O. sativa and O.
      glaberrima) and 13 wild accessions, in addition to a CC-genome species (O.
      officinalis) that was used as an outgroup. Analyses of the combined sequence data
      set from different sources provide a much better resolution of the AA-genome
      species than the individual data set, indicating the limitation of a single gene
      in phylogenetic reconstruction. The phylogeny based on the combined data set
      demonstrated an apparent grouping of the AA-genome Oryza species that was well
      associated with their geographic origin, although the Australian O. meridionalis
      showed its affinity with the African species. The geographic pattern of the
      phylogenetic relationship was probably attributed to the frequent genetic
      exchange and introgression among the AA-genome species from the same continents.
      In addition, Asian cultivated rice O. sativa showed its close relation to O.
      rufipogon and O. nivara, whereas African cultivated rice O. glaberrima was
      closely linked to O. barthii and O. longistaminata, indicating the independent
      domestication of the two cultivated species in different geographic locations.

PMID- 17221299
TI  - UCP2 and 3 deletion screening and distribution in 15 pig breeds.
AB  - The uncoupling protein family is a mitochondrial anion carrier family. It plays
      an important role in the biological traits of animal body weight, basal metabolic
      rate and energy conversion. Using PCR and PCR-SSCP, we scanned the porcine
      uncoupling protein 2 gene (UCP2) and uncoupling protein 3 gene (UCP3) and found
      seven deletion sites, three in UCP2 and four in UCP3. The deletions in 15 pig
      breeds showed that deletion influenced weight. The genotype compounding of seven
      deletion sites in 15 pig breeds had significant effects on performance traits of
      the pig, such as body weight. We predicted the potential protein factor binding
      sites using the transcription factor analysis tool TFSearch version 1.3 online.
      Two deletions (1830 nt and 3219 nt) in UCP3 were found to change the
      transcriptional factor sites. The 16 bp deletion in 1830 nt added a SP1 site and
      a 6 bp deletion in 3219 nt removed two MZF1 sites. Seven deletion polymorphisms
      were covered in introns of linkage genes of UCP2 and UCP3, showing that UCPs have
      conservation and genetic reliability.

PMID- 17221301
TI  - Relationship between mRNA stability and length: an old question with a new twist.
AB  - The half-life of individual mRNA plays a central role in controlling the level of
      gene expression. However, the determinants of mRNA stability have not yet been
      well defined. Most previous studies suggest that mRNA length does not affect its
      stability. Here, we show significant negative correlations between mRNA length
      and stability in human and Escherichia coli, but not in Saccharomyces cerevisiae
      or Bacillus subtilis. This finding suggests the possibility that endonucleolytic
      attacks by RNA endonuclease and/or mechanical damage may strongly influence mRNA
      stability in both prokaryotes and eukaryotes.

PMID- 17221302
TI  - Evolution of the Spiroplasma P58 multigene family.

PMID- 17221305
TI  - Severe pulmonary toxicity in patients with leiomyosarcoma after treatment with
      gemcitabine and docetaxel.

PMID- 17221304
TI  - Intrastriatal injection of hypoxanthine reduces striatal serotonin content and
      impairs spatial memory performance in rats.
AB  - The aim of this study was to investigate the effects of intrastriatal injection
      of hypoxanthine, a metabolite accumulated in Lesch-Nyhan disease, on rats'
      performance in the Morris water maze tasks, along with the monoamine content in
      striatum of rats. Male adult Wistar rats were divided in two groups: (1) saline
      injected and (2) hypoxanthine-injected group. Seven days after solutions
      infusion, animals were trained in the Morris Water Maze or were sacrificed for
      evaluation of the striatal monoamine content. Results show that hypoxanthine
      administration caused impairment on spatial navigation in the acquisition phase
      in reference memory task in the Morris Water Maze, as well as in the latency to
      cross over the platform location in probe trial, when compared to the saline
      group (control). Hypoxanthine also altered rat performance in the working memory.
      Although striatal dopamine metabolites content did not change, treated animals
      showed a reduction of tissue levels of serotonin (5-HT) and 5- hydroxyl
      indoleacetic acid (5-HIAA). These results show that intra-striatal hypoxanthine
      administration provoked impairment of spatial learning/memory in rats without
      affecting striatal dopaminergic system, although serotonergic pathways seem to
      have been affected.

PMID- 17221303
TI  - Energy metabolism is compromised in skeletal muscle of rats chronically-treated
      with glutaric acid.
AB  - Glutaric acidemia type I (GA I) (GA I, McKusick 23167; OMIM # 231670) is an
      autosomal recessive metabolic disorder caused by glutaryl-CoA dehydrogenase
      deficiency (EC 1.3.99.7). Clinically, the disease is characterized by
      macrocephaly, hypotonia, dystonia and diskinesia. Since the pathophysiology of
      this disorder is not yet well established, in the present investigation we
      determined a number of energy metabolism parameters, namely (14)CO(2) production,
      the activities of the respiratory chain complexes I-IV and of creatine kinase, in
      tissues of rats chronically exposed to glutaric acid (GA). High tissue GA
      concentrations (0.6 mM in the brain, 4 mM in skeletal muscle and 6 mM in plasma)
      were induced by three daily subcutaneous injections of saline-buffered GA (5
      micromol x g(-1) body weight) to Wistar rats from the 5th to the 21st day of
      life. The parameters were assessed 12 h after the last GA injection in cerebral
      cortex and middle brain, as well as in skeletal muscle homogenates of GA-treated
      rats. GA administration significantly inhibited the activities of the respiratory
      chain complexes I-III and II and induced a significant increase of complex IV
      activity in skeletal muscle of rats. Furthermore, creatine kinase activity was
      also inhibited by GA treatment in skeletal muscle. In contrast, these
      measurements were not altered by GA administration in the brain structures
      studied. Taken together, it was demonstrated that chronic GA administration
      induced an impairment of energy metabolism in rat skeletal muscle probably due to
      a higher tissue concentration of this organic acid that may be possibly
      associated to the muscle weakness occurring in glutaric acidemic patients.

PMID- 17221306
TI  - Tests of independence for censored bivariate failure time data.
AB  - Bivariate failure time data is widely used in survival analysis, for example, in
      twins study. This article presents a class of chi2-type tests for independence
      between pairs of failure times after adjusting for covariates. A bivariate
      accelerated failure time model is proposed for the joint distribution of
      bivariate failure times while leaving the dependence structures for related
      failure times completely unspecified. Theoretical properties of the proposed
      tests are derived and variance estimates of the test statistics are obtained
      using a resampling technique. Simulation studies show that the proposed tests are
      appropriate for practical use. Two examples including the study of infection in
      catheters for patients on dialysis and the diabetic retinopathy study are also
      given to illustrate the methodology.

PMID- 17221307
TI  - Vasoactivity of blood vessels using a novel isovolumic myograph.
AB  - The vasoactivity of blood vessel is impaired by cardiovascular disease. The ex
      vivo measurements of vasoactivity (wire and pressure myographs) have some
      inherent difficulties in the characterization of pharmacodynamics and
      biomechanics. Here, we introduce a novel isovolumic myograph which allows
      simultaneous measurement of both dynamic pressure and dimensional changes during
      vasoconstriction or vasodilation. The principle of the isovolumic myograph is
      based on the utility of a hydraulically closed system with low compliance such
      that contraction against an incompressible fluid increases the pressure with the
      closed system while dilation decreases it. We demonstrate the sensitivity and
      utility of the new technique by the response of elastic (carotid), muscular
      (femoral) arteries, and femoral veins. The results show characteristic dynamic
      pressure response for each vessel type. Furthermore, our results show a Hill-type
      equation for the tension-velocity relation for smooth muscles as well as
      characteristic curves for each contraction. These novel findings for blood
      vessels will advance our knowledge of endothelium and vascular smooth muscle
      mechanics and pharmacodynamics.

PMID- 17221308
TI  - Unicorns or Tiger Woods: are lie detection experts myths or rarities? A response
      to on lie detection "wizards" by Bond and Uysal.
AB  - Bond and Uysal (this issue) complain that expert lie detectors identified by
      O'Sullivan and Ekman (2004) are statistical flukes. They ignore one class of
      experts we have identified and misrepresent the procedures we use to identify the
      others. They also question the psychometric validity of the measures and protocol
      used. Many of their points are addressed in the chapter they criticize. The
      fruitfulness of the O'Sullivan-Ekman protocol is illustrated with respect to
      improved identification of expert lie detectors, as well as a replicated pattern
      of errors made by experts from different professional groups. The statistical
      arguments offered confuse the theoretical use of the binomial with the empirical
      use of the normal distribution. Data are provided that may clarify this
      distinction.

PMID- 17221309
TI  - On lie detection "wizards".
AB  - M. O'Sullivan and P. Ekman (2004) claim to have discovered 29 wizards of
      deception detection. The present commentary offers a statistical critique of the
      evidence for this claim. Analyses reveal that chance can explain results that the
      authors attribute to wizardry. Thus, by the usual statistical logic of
      psychological research, O'Sullivan and Ekman's claims about wizardry are
      gratuitous. Even so, there may be individuals whose wizardry remains to be
      uncovered. Thus, the commentary outlines forms of evidence that are (and are not)
      capable of diagnosing lie detection wizardry.

PMID- 17221310
TI  - Reversible jump Markov chain Monte Carlo for deconvolution.
AB  - To solve the problem of estimating an unknown input function to a linear time
      invariant system we propose an adaptive non-parametric method based on reversible
      jump Markov chain Monte Carlo (RJMCMC). We use piecewise polynomial functions
      (splines) to represent the input function. The RJMCMC algorithm allows the
      exploration of a large space of competing models, in our case the collection of
      splines corresponding to alternative positions of breakpoints, and it is based on
      the specification of transition probabilities between the models. RJMCMC
      determines: the number and the position of the breakpoints, and the coefficients
      determining the shape of the spline, as well as the corresponding posterior
      distribution of breakpoints, number of breakpoints, coefficients and arbitrary
      statistics of interest associated with the estimation problem. Simulation studies
      show that the RJMCMC method can obtain accurate reconstructions of complex input
      functions, and obtains better results compared with standard non-parametric
      deconvolution methods. Applications to real data are also reported.

PMID- 17221311
TI  - The genetics of voting: an Australian twin study.
AB  - Previously we and others have shown evidence for genetic influences on political
      attitudes and sociodemographic indicators (Martin 1987; Posner et al. 1996;
      Truett et al. 1992; Eaves et al. 1999). However, the nature of the relationship
      between political attitudes, social indictors and voting behavior has not been
      investigated. While heritability estimates for social and political attitudes
      have been reported in previous research, the heritability for vote choice has
      not. Furthermore, if vote choice is heritable, it is unclear whether the
      heritable component can be accounted for through the genetic influence on related
      social and political traits, or if there exists a unique genetic component
      specific to voting behavior. In mailed surveys of adult Australian twins, we
      asked respondents to indicate their usual voting preference as well as attitudes
      on contemporary individual political items. When vote choice was dichotomized as
      Labor versus Conservative, twin correlations were r (mz) = 0.81 (1,661 pairs),
      and r (dz) = 0.69 (1,727 pairs) consistent with modest genetic influence (a (2) =
      0.24). However, multivariate genetic analysis showed no unique genetic
      contribution to voting preference; rather, the genetic influence in vote choice
      could be explained by shared genetic influences in perceived social class, church
      attendance and certain key political attitude items.

PMID- 17221312
TI  - Fibroblast interaction with carboxymethylchitosan-based hydrogels.
AB  - The interaction between L929 cells and carboxymethylchitosan (CM-chitosan)-based
      hydrogels, hydrogels from pure CM-chitosan and its blends, was examined in this
      study. Cytotoxicity of all materials was also assessed. The cellular morphology
      and behavior on the surfaces of the hydrogels were observed by scanning electron
      microscopy (SEM). The effects of various parameters, e.g., type and content of
      blended polymers, surface structure of hydrogels, and steaming condition used for
      the preparation of the hydrogels, on the cell-material response were
      investigated. The results of the cytotoxicity test revealed that all hydrogels
      were non-cytotoxic. The SEM micrographs demonstrated that the cells proliferated
      and spread onto a porous CM-chitosan sample. Better cell spreading was found on a
      flat surface of a CM-chitosan film. Rounded cells were observed when poly(vinyl
      alcohol) (PVA) was incorporated into CM-chitosan. Fewer cells were found when the
      content of PVA increased. Spherical clusters of the aggregated cells existed in
      the blends with ultra high viscosity carboxymethylcellulose (CM-cellulose). In
      contrast, with the use of low viscosity CM-cellulose, the cells appeared more
      spreading. The attached cells on the CM-chitosan film steamed at the highest
      temperature and longest period appeared to spread the most among all tested
      steaming conditions.

PMID- 17221313
TI  - In vitro biodegradation and biocompatibility of gelatin/montmorillonite-chitosan
      intercalated nanocomposite.
AB  - The intercalated nanocomposite of gelatin/montmorillonite-chitosan (Gel/MMT-CS)
      was prepared via the solution intercalation process. In vitro degradation tests
      showed that the nanocomposite had a lower degradation rate than Gel-CS composite.
      And the introduced intercalation structure endowed Gel/MMT-CS nanocomposite with
      a controllable degradation rate when changing the MMT content. Cells attachment,
      spread and proliferation on the Gel/MMT-CS membranes were investigated by
      scanning electron microscopy (SEM) and mitochondrial activity assay. The results
      provided evidences of good adhesion, proliferation and morphology of rat stromal
      stem cells on Gel/MMT-CS membranes compared to the tissue culture plates (TCPs),
      making the Gel/MMT-CS nanocomposite a promising candidate towards tissue
      engineering.

PMID- 17221314
TI  - The effect of oxide thickness on osteoblast attachment and survival on NiTi
      alloy.
AB  - NiTi alloy is used in various medical applications and the surface titanium oxide
      layer produced naturally or enhanced artificially has been thought to offer a
      protecting film against allergic and toxic effects of nickel (Ni). In this study,
      we investigated the effect of different oxide layer thicknesses on the survival
      and attachment of osteoblastic cells (ROS-17/2.8). AFM, X-ray diffraction and
      electrical resistance measurements were used to analyze the surface properties of
      oxidized NiTi samples and the effect of oxidation on material properties. The
      results clearly showed that straight correlation between oxide thickness and
      cellular well-being cannot be maid. However, the different thicknesses of oxide
      layer on NiTi had surprising impacts on cellular responses and also to the
      properties of the metal alloy.

PMID- 17221315
TI  - Biocompatible porous ceramics for the cultivation of hematopoietic cells.
AB  - Porous ceramics made of alumina and hydroxyapatite were created using a protein
      foaming method. Porosity and pore size distribution were successfully varied by
      means of chemical modification of the foaming protein Bovine serum albumin (BSA).
      The effectiveness of the BSA and of its chemical modifications as well as the
      influence of the dispersing agent were investigated using synchrotron tomography.
      Resulting porous ceramic materials were used as three-dimensional substrates for
      the cultivation of human peripheral stem cells. The cells proliferated and
      differentiated in culture. Five cell lines consistent with human blood cell lines
      were observed.

PMID- 17221316
TI  - Morphology and mechanical stability of amyloid-like peptide fibrils.
AB  - Synthetic, amyloid-like peptide fibrils have recently attracted interest as a
      novel, potentially biocompatible material for applications in biotechnology and
      tissue-engineering. In this paper, we report atomic force microscopy (AFM)
      studies of the morphology and mechanical stability of fibrils self-assembled in
      vitro from the short peptide TTR(105-115), which serves as a model system for
      amyloid fibrils. It forms predominantly straight rods of approximately 1 microm
      in length and of diameters between 7 nm and 12 nm. We found polymorphism, with
      some fibrils exhibiting an unstructured morphology and others showing a regular,
      longitudinal surface pattern of 90 nm periodicity. Contact mode AFM-imaging in
      air was utilised to perform mechanical tests of individual fibrils on the
      nanometer scale with a defined, vertical force in the nN-range applied by the AFM
      tip. Above 100 nN, all fibrils showed a permanent, mechanical deformation whereas
      below 40 nN, fibrils remained unaffected. Tapping-mode AFM-imaging in water led
      to fibril decomposition within 1.5 h whereas tapping-mode imaging in air left
      fibrils intact. Additional investigations by circular-dichroism spectroscopy
      showed that dispersed fibrils were structurally stable in aqueous solution
      between pH 3 and pH 8, and in sodium phosphate buffer of concentration between 50
      mM and 1 M.

PMID- 17221317
TI  - Preliminary work on the development of a novel detection method for osteoporosis.
AB  - Osteoporosis affects both the organic and mineral phases of bone resulting in a
      decrease in resistance to fracture. Dual x-ray absorptiometry (DEXA) scans are
      used for diagnosing osteoporosis, which is conventionally characterised by a
      decrease in mineral density. Unfortunately, some patients who suffer osteoporotic
      fractures have normal bone density, because both the organic and the mineral
      phase are affected. However, there are currently no methods of evaluating the
      health of the organic phase. Patients undergoing treatment for osteoporosis have
      reported hardening of their fingernails. As the properties of nail and bone may
      be linked in a comparable, measurable way, this work used both mechanical (nano
      indentation) and chemical (Raman spectroscopy) methods to evaluate differences
      between fingernails sourced from osteoporotic and non-osteoporotic patients. The
      difference in mean modulus between the nails sourced from the groups was 1.1 GPa.
      The disulphide bond content of fingernail samples from each group was measured by
      Raman spectroscopy and disulphide bond content of fingernail was found to be
      significantly lower in the osteoporotic group. It can be concluded that a
      relationship between the mechanical and chemical properties of nail and bone may
      exist in a measurable way. This work has suggested that changes in the organic
      phase of bone are reflected in similar proteins, such as keratin, from which
      fingernails are composed. Collagen and keratin are two distinct structural
      proteins, but they share the need for protein sulphation and disulphide bond
      formation, via cysteine, for their structural integrity. A disorder of either
      process should lead to disordered collagen and keratin synthesis.

PMID- 17221319
TI  - Parental smoking and adolescent smoking stages: the role of parents' current and
      former smoking, and family structure.
AB  - This study examined the role of parents' current and former smoking in predicting
      adolescent smoking acquisition stages. Participants were 7,426 students from 33
      schools in the Netherlands. Participants' survey data were gathered at baseline
      and at two-year follow-up. Logistic regression models showed that parental
      smoking status was not only predictive of transitions from never smoking to
      trying smoking, monthly smoking, or daily smoking, but also of the progression
      from trying smoking to daily smoking. Further, although parental former smoking
      was weaker associated with progressive adolescent smoking transitions than
      current parental smoking, however absence of parental smoking history was most
      preventive. Compared to the situation in which both parents had never smoked,
      cessation of parental smoking after the child was born was associated with an
      increased risk for children to smoke. Adolescents living in a single-parent
      family were at greater risk of smoking than adolescents living in an intact
      family with both mother and father. In sum, the role of parental smoking is not
      restricted to smoking onset and is present throughout different phases of the
      acquisition process. Results support the delayed modeling hypothesis that
      parental smoking affects the likelihood for children to smoke even when parents
      quit many years before. Children living in single-parent families are only
      exposed to the behaviour of one parent; in two-parent families the behaviour from
      one parent may magnify or buffer the behaviour of the other parent.

PMID- 17221318
TI  - Endothelins mediate neutrophil activation, ProMMP-9 release and endothelial cell
      detachment.
AB  - Neutrophils isolated from human peripheral blood added to a monolayer of human
      endothelial cells (ECV-304 cell line) stimulated with LPS (100 ng ml(-1))
      resulted in: (a) neutrophil activation, measured by spreading and release of
      leukotriene B(4) (LTB(4)); (b) neutrophil degranulation, measured by release of
      matrix pro-metalloproteinase-9 (proMMP-9) and (c) loss of the monolayer integrity
      due to detachment of the endothelial cells. Stimulation of endothelial cells with
      tumor necrosis factor-alpha (TNF-alpha 10 ng ml(-1)) or interleukin-1 (IL-1; 10
      ng ml(-1)) induced a similar dose-dependent increase in the neutrophil activation
      and endothelial cell detachment. Pre-treatment of LPS-activated ECV-304 cells
      with [Phe22]BigET-1(19-37) (10(-9) M; an inhibitor of endothelin converting
      enzyme (ECE)) or addition of BQ-123 (10(-6) M; a selective endothelin A (ET(A))
      receptor antagonist) to the co-cultures, significantly reduced neutrophil
      spreading (50-70% inhibition) as well as the levels of LTB(4) (70-100%
      inhibition) and proMMP-9 (40-50% inhibition) in the co-culture supernatants. In
      addition, the detachment of endothelial cells was also reduced (60-75%
      inhibition). Moreover, the exogenous addition of ET-1 (10(-9) M) to neutrophil
      suspensions induced neutrophil spreading and release of LTB(4) and proMMP-9.
      Taken together, these findings indicate that neutrophils added to stimulated
      endothelial cells in the co-culture system employed in this study, get activated
      by products of these cells and degranulate. In parallel, the detachment of
      endothelial cell monolayer from the culture plates, possibly by the action of
      neutrophil granule-derived gelatinases, is observed. Endothelins (ETs) produced
      by the endothelial cells are suggested to play an essential role in these
      phenomena.

PMID- 17221320
TI  - Looks aren't everything: pseudohomophones prime words but nonwords do not.
AB  - After examining literature that deals with phonological and orthographic effects
      associated with pseudohomophones, the current effort deviates from the norm by
      using fewer pseudohomophones (20%) and extending the lags between primes and
      targets (M = 8). Word and pseudohomophone primes were found to facilitate lexical
      decision response latencies to word targets. Response latencies to word targets
      were not influenced by nonword primes, however. The presence of pseudohomophone
      effects was demonstrated by longer response latencies and higher error rates for
      pseudohomophones (e.g., DREEM) that were equated in orthography to nonword
      controls (e.g., DROAM). Despite the frequency effect observed for base words, the
      pseudohomophones did not exhibit an effect of base word frequency. The results
      suggest that phonological codes exert an influence on lexical representation but
      are not frequency sensitive.

PMID- 17221322
TI  - A dramatic response to rituximab in a patient with resistant thrombotic
      thrombocytopenic purpura (TTP) who developed acute stroke.
AB  - BACKGROUND: Refractory condition can occur in 10-30% of all cases of thrombotic
      thrombocytopenic purpura despite increased frequency of total plasma exchange.
      Rituximab can affect the clinical outcome of the refractory cases. However,
      little is known about usefulness of rituximab on central nervous system
      involvement mimicking acute ischemic stroke. METHODS: We report the case of a
      woman with refractory thrombotic thrombocytopenic purpura who developed an acute
      onset right sided paralysis, dysarthria, and central facial paralysis, suggestive
      of cerebrovascular accident while under plasma exchange, corticosteroid, and
      vincristine therapy. RESULTS: After initiation of rituximab (375 mg/m(2) weekly
      for 4 weeks), a dramatic response occurred and the patient's neurologic function
      recovered fully within days. Sustained remission was achieved, and the patient
      was well 1 year after her admission, while she was on azathioprine treatment.
      CONCLUSION: This report suggests that rituximab can provide a good outcome of the
      dramatic central nervous system involvement in patients with thrombotic
      thrombocytopenic purpura.

PMID- 17221323
TI  - Lemierre syndrome variant: Staphylococcus aureus associated with thrombosis of
      both the right internal jugular vein and the splenic vein after the exploration
      of a river cave.
AB  - BACKGROUND: Lemierre syndrome is a rare and potentially fatal entity
      characterized by septic emboli from thrombosis of the internal jugular vein after
      oropharyngeal infection. The etiologic agent is not always an anaerobic
      bacterium. We report a patient with a Lemierre syndrome variant who presented
      with thrombosis of both the right internal jugular vein and the splenic vein as
      well as septic pulmonary emboli caused by Staphylococcus aureus, which proved
      resistant to methicillin, amoxicillin, and ciprofloxacin. The patient was thought
      to have acquired the infection during the exploration of a river cave in Turkey
      10 days before his admission to the hospital. Such caves are natural reservoirs
      of infectious microorganisms. METHODS: The patient had a physical examination,
      coagulation screening tests, tests of thrombin generation and fibrinolysis,
      coagulation inhibitors, activated protein C resistance, early and late
      serological tests (including autoantibodies), computed tomographic studies of the
      chest and abdomen, and bacterial examination of peripheral blood. Bacterial
      investigations were made on samples collected from the river cave. RESULTS: After
      having undergone a 6 week course of antimicrobial treatment and anticoagulant
      therapy, the patient recovered from the infection with no residual complications,
      and the signs and symptoms of Lemierre syndrome resolved. CONCLUSION: The results
      probably indicate an exposure of the patient to soil-based Staphylococcus aureus.
      This observation suggests the action of environmental factors that may contribute
      to the development of this rare syndrome.

PMID- 17221321
TI  - Relevance of donepezil in enhancing learning and memory in special populations: a
      review of the literature.
AB  - This review discusses the laboratory and clinical research supporting the
      rationale for the efficacy of donepezil (Aricept USA) in enhancing cognition in
      autism, Alzheimer disease, Down syndrome, traumatic brain injury, Attention
      Deficit Hyperactivity Disorder (ADHD), and schizophrenia. While preliminary
      animal models have shown effective, human studies exclusive of Alzheimer disease
      are sparse. Although attention and memory are unlikely a sole operation of the
      cholinergic system, evidence indicates a promising direction for further
      examination of this hypothesis in autism. Studies that examine changes in
      operationally defined behaviors and reliable and valid measure of changes in
      attention and memory are needed.

PMID- 17221325
TI  - Effects of low osmolar contrast (iomeprol) on haemorheology and platelet
      activation in patients with coronary artery disease.
AB  - BACKGROUND: Non-ionic low osmolar contrast agents are widely used during coronary
      angiography. As these agents cause activation of thrombotic pathways in vitro,
      this may have potentially significant clinical impact. However, limited evidence
      exists as to their in vivo effects from selective coronary cannulation. METHODS:
      We initially performed an in vitro experiment to assess the effect of serial
      contrast (Iomeprol 300, Bracco) dilution on platelet indices [mean platelet count
      (MPC), platelet volume (MPV), platelet granularity (MPG)]. The in vivo effect of
      contrast injection on platelet activation markers [soluble P-selectin (sPsel),
      soluble CD40 ligand (sCD40L)], MPC, MPV, MPG, haemoglobin and haematocrit was
      subsequently determined in 35 patients (mean age 58 +/- 11; 22 males) undergoing
      cardiac catheterisaton. RESULTS: No significant in vitro effect of contrast on
      MPC or MPV was seen but there was a significant increase in MPG (p = 0.40, 0.10
      and 0.01, respectively). In the in vivo study, there was a reduction in mean
      haemoglobin and haematocrit levels, suggesting an average increase in plasma
      volume of 6.5 +/- 5.8%. The in vivo effect of Iomeprol was associated with an
      unadjusted reduction in sPsel concentrations (p = 0.04) and MPV (p < 0.05), with
      denser platelets (p < 0.05). There was no difference in MPC or sCD40L
      concentration (both p = NS). After adjustment for the haemodilution effect, no
      significant reduction in P-sel levels was seen with contrast (p = 0.27), although
      the adjusted post-contrast change in MPG (p = 0.01), MPC (p = 0.01) and sCD40L (p
      < 0.05) levels were significant. CONCLUSION: Low osmolar contrast led to a
      minimal effect on soluble and physical indices of platelets within the coronary
      artery, primarily due to plasma volume expansion.

PMID- 17221324
TI  - Heparin resistance in acute coronary syndromes.
AB  - BACKGROUND: Maintaining a therapeutic level of anticoagulation with
      unfractionated heparin remains a major challenge for clinicians because of the
      wide variability of patient responses, which may be explained by variable binding
      of heparin to plasma proteins. Direct thrombin inhibitors may offer an advantage
      in more predictable anticoagulation. METHODS: Plasma samples from normal
      volunteers, stable coronary artery disease (CAD) patients, unstable angina
      patients, and acute myocardial infarction patients were obtained. A fixed
      concentration of heparin (.13 U/ml) or bivalirudin (1.6 microg/ml) was added to
      plasma from each of the four study groups and measurement of the APTT was
      performed. In addition, a pool of plasma from patients with acute MI was diluted
      in pooled normal plasma, and heparin or bivalirudin was added to the plasma
      preparation and APTT measurements performed. RESULTS: In heparin-treated plasma
      samples, mean APTT values were 443 +/- 137% baseline for normal volunteers, 347
      +/- 116% for patients with stable CAD, 290 +/- 124% for patients with unstable
      angina (p < 0.05), and 230 +/- 120% for patients with acute MI (p < 0.05). APTT
      did not differ across the four groups treated with bivalirudin. There was a much
      higher degree of variability in APTT values in heparin treated controls (272%
      671%, SD approximately 30%) compared to bivalirudin treated controls (284-499%,
      SD approximately 12%). When the "acute MI pool" was diluted in pooled normal
      plasma at fixed concentrations of either bivalirudin (1.6 mug/ml) or heparin
      (0.13 U/ml), there was a sharp decrease in heparin activity from 407% baseline
      (at 0% acute MI pool) to values as low as 126% baseline (at 100% acute MI pool).
      A markedly different pattern was seen in the bivalirudin treated samples, where a
      trend towards decreased APTT values was seen only at the 100% acute MI pool.
      CONCLUSION: Both heparin variability and resistance may limit optimal
      antithrombotic therapy with heparin in patients with ACS and constitutes a
      potential advantage of direct antithrombin blockade with bivalirudin.

PMID- 17221326
TI  - In vitro shear stress modulates antithrombogenic potentials of human endothelial
      progenitor cells.
AB  - BACKGROUND: Recent study suggested that endothelial progenitor cells (EPCs), a
      novel therapeutic approach for endothelial dysfunction, present limited
      antithrombogenic potentials. However, few attempts have been done to improve the
      antithrombogenic potentials of EPCs. Our previous study proved that in vitro
      shear stress contributes to the increase in t-PA production by human EPCs. Here,
      we further investigated whether in vitro shear stress contributes to the
      secretion of antithrombogenic substances including plasminogen activator
      inhibitor-1 (PAI-1) and prostaglandin I(2) (PGI(2)) by human EPCs. METHODS: The
      peripheral blood mononuclear cells of healthy subjects were induced into EPCs.
      Then the human EPCs were treated with four levels of shear stress including
      stationary condition low media and high flow shear stress. The production of PAI
      1 and 6-keto-prostaglandin F1(1alpha)(6-Keto-PGF(1alpha)) by human EPCs with
      shear stress treatment were measured. RESULTS: In vitro medium and high flow
      shear stress inhibited PAI-1 secretion by human EPCs, but low flow shear stress
      had no effect on PAI-1 secretion by human EPCs. All levels of shear stress
      significantly increased 6-Keto-PGF(1alpha )production by human EPCs in a dose
      dependent manner. CONCLUSIONS: The present study demonstrates that in vitro shear
      stress can promote PGI(2 )secretion and inhibit PAI-1 secretion by human EPCs,
      which improves the antithrombogenic potentials of human EPCs.

PMID- 17221327
TI  - The duration of anticoagulation bridging therapy in clinical practice may
      significantly exceed that observed in clinical trials.
AB  - BACKGROUND: Clinical trials involving frequent, standardized monitoring of the
      international normalized ratio (INR) demonstrated that a short course of low
      molecular-weight-heparin (LMWH) can successfully bridge patients to oral
      anticoagulation. However, rigidly performed INR testing is often not feasible in
      the outpatient setting in actual clinical practice. The purpose of this study was
      to determine if the anticoagulation results of clinical trials of LMWH bridging
      therapy are also achieved in a single-center clinical practice setting. METHODS:
      We conducted a retrospective analysis of 100 patients initiating warfarin while
      receiving LMWH under the care of a university-based anticoagulation management
      service. RESULTS: Mean patient age was 56.1 +/- 16.3 years. The commonest
      indications for anticoagulation were venous thrombosis (57%) and atrial
      fibrillation (25%). Mean initial warfarin dose was 5.1 +/- 1.8 mg/day; 30% of
      patients received antiplatelet therapy. The mean total duration of LMWH therapy
      was 12.0 +/- 8.2 days, of which 9.8 +/- 8.0 days (median 7.5 days; interquartile
      range 4.3-13.0 days) occurred in the outpatient setting. Forty-one percent of
      patients received outpatient LMWH for < 7 days, 40% for 7-14 days, and 19% for >
      14 days. A mean of 3.9 +/- 2.0 INRs were performed during LMWH therapy.
      Complications included 11 minor and 1 major bleeding episodes and 1 thrombotic
      event. CONCLUSIONS: The duration of LMWH bridging therapy in practice may be
      significantly greater than previously reported in clinical trials, and the
      incidence of patients requiring prolonged (>14 days) LMWH therapy is relatively
      high. Outpatient LMWH as employed in clinical practice safely bridges patients to
      oral anticoagulation. Strategies to shorten the duration of LMWH therapy are
      needed and are likely to improve clinical outcomes and reduce health care
      expenses. In prospective clinical trials low-molecular-weight-heparin (LMWH) has
      proven effective in transitioning patients with venous thromboembolic disease to
      therapeutic warfarin anticoagulation. However, it is unknown if the
      anticoagulation results obtained in these trials, which involved rigidly
      performed anticoagulation monitoring, are achieved in standard clinical practice
      involving patients with a variety of indications for anticoagulation. We
      conducted a retrospective analysis of 100 patients initiating warfarin while
      receiving LMWH under the management of a university-based anticoagulation
      management service. The mean total duration of LMWH therapy was 12.0 +/- 8.2
      days, of which 9.8 +/- 8.0 days (median 7.5 days; interquartile range 4.3-13.0
      days) occurred in the outpatient setting. Forty-one percent of patients received
      outpatient LMWH for <7 days, 40% for 7-14 days, and 19% for >14 days. We conclude
      that the duration of LMWH bridging therapy in practice may be significantly
      greater than previously reported in clinical trials, and the incidence of
      patients requiring prolonged (>14 days) LMWH therapy is relatively high.

PMID- 17221328
TI  - Descriptive analysis of the process and quality of oral anticoagulation
      management in real-life practice in patients with chronic non-valvular atrial
      fibrillation: the international study of anticoagulation management (ISAM).
AB  - BACKGROUND/OBJECTIVES: Expert oral anticoagulation management is the key to good
      outcomes and is performed variably in different health care systems throughout
      the world. We set out to assess the quality of anticoagulation management in five
      countries in patients receiving vitamin K antagonists (VKAs) for stroke
      prophylaxis in chronic non-valvular atrial fibrillation (NVAF), and to compare
      the anticoagulation management practices in these countries. METHODS AND RESULTS:
      This was a retrospective, multi-centre cohort study in the United States, Canada,
      France, Italy, and Spain. About 1,511 patients were randomly recruited from
      representative practices (routine medical care (RMC) in the US, Canada, and
      France; anticoagulation clinics in Italy and Spain) and data pertaining to their
      oral anticoagulation care were abstracted from their medical records. The
      predominant anticoagulant in use was warfarin in the US, Canada, and Italy;
      acenocoumarol in Spain; and fluindione in France. Documentation of care was poor
      in the US, Canada, and France, countries where RMC was studied. Percent INRs or
      time-in-therapeutic range was greater in the two anticoagulation clinic samples
      compared with the RMC samples. CONCLUSION: Oral anticoagulation care varies
      considerably from country to country. Findings suggest that anticoagulation
      clinic care (ACC) may provide better outcomes as assessed by international
      normalized ratio (INR) time-in-range. Physicians tend to under treat more than
      over treat. Finally, documentation of care is often inadequate. Condensed
      Abstract Oral anticoagulation management (routine medical care or anticoagulation
      clinic care) was retrospectively assessed in 5 countries using a uniform,
      structured assessment tool. Major management differences were detected,
      especially between anticoagulation clinic care and routine care. Documentation
      was often a problem in the latter setting. Less time in therapeutic INR range was
      noted in routine medical care. Findings suggest that anticoagulation clinic care
      may provide better outcomes as assessed by international normalized ratio (INR)
      time-in-range. Physicians tend to under treat more than over treat. Finally,
      documentation of care is often inadequate.

PMID- 17221329
TI  - The association of P-selectin glycoprotein ligand-1 VNTR polymorphisms with
      coronary stent restenosis.
AB  - BACKGROUND: P-selectin and P-selectin glycoprotein ligand-1 (PSGL-1) regulate the
      initial interactions between leukocytes, activated platelets and endothelial
      cells. Recently, a variable number of tandem repeats (VNTR) polymorphism in PSGL
      1 gene affecting the length of the extracellular domain of PSGL-1 and the
      distance of the P-selectin binding site to the cell surface has been described.
      There are limited numbers of studies reporting PSGL-1 polymorphism might affect
      the inflammatory response and thrombosis. We explored the association between
      PSGL-1 VNTR polymorphisms (especially AB genotype that has the most deformed
      configuration of the binding site) and the development of coronary stent
      restenosis and stent thrombosis in patients with coronary artery disease (CAD).
      MATERIALS AND METHODS: Eighty-seven patients with in-stent restenosis and 93
      patients with patent coronary stents were included into the study. The
      distributions of age, gender, hypertension, diabetes, smoking, total cholesterol
      and triglyceride levels were similar between the groups. Genomic DNAs were
      obtained by standard methods from whole blood samples. Specific primers were used
      to amplify PSGL-1 gene by polymerase chain reaction (PCR). RESULTS: Three alleles
      and 5 different genotypes were detected. In the in-stent restenosis group; allele
      frequencies were 79.5% for A allele, 18.1% for B allele and 2.4% for C allele and
      in the patent stent group; allele frequencies were 79.3% for A allele, 20.1% for
      B allele and 0.6% for C allele. The allele frequencies were similar between the
      in-stent restenosis group and patent stent group (P = 0.97 for A allele, P = 0.73
      for B allele and P = 0.19 for C allele). Genotype distributions were also similar
      between the groups. There were not any significant associations between PSGL-1 AB
      genotype and stent restenosis (31.3% vs. 27.2%, P = 0.54), repetitive stent
      restenosis (33.3% vs. 28.8%, P = 0.82) or in-stent thrombosis (44.4% vs. 28.2%, P
      = 0.37). In neither male patients nor female patients, there was any significant
      association between AB genotype and restenosis (32.2% vs. 24.3% P = 0.31 and
      29.2% vs. 38.9% P = 0.51, respectively). However, among patients with a family
      history of early CAD, significantly higher percentage of AB genotype was found in
      those with stent restenosis (41.4% vs. 18.8%, P = 0.03). CONCLUSIONS: No
      significant association was found between PSGL-1 VNTR polymorphisms and in-stent
      restenosis. However, in patients with a family history of early CAD presence of
      PSGL-1 AB genotype might increase the risk of in-stent restenosis.

PMID- 17221331
TI  - Chronic oral anticoagulant therapy for extrahepatic visceral thrombosis is safe.
AB  - BACKGROUND: Patients with hypercoagulability may thrombose visceral veins with
      resultant portal hypertension, esophagogastric varices, and hemorrhage. The role
      of chronic oral anticoagulant therapy in such patients is unclear. On the one
      hand, such patients are prone to significant hemorrhage and thus anticoagulant
      therapy may seem contraindicated. On the other hand, because the causal
      pathophysiology is typically hypercoagulability, it would seem rational to treat
      these patients with chronic anticoagulant therapy in order to both prevent other
      visceral and systemic thromboses and perhaps, over time, reduce the degree of
      portal hypertension. Experience and poor prognosis associated with the more
      common portal hypertension due to hepatic cirrhosis may bias judgment. METHODS:
      We retrospectively reviewed the course of chronic oral anticoagulant therapy
      regarding both the safety and effectiveness using our long-term follow-up of a
      cohort of seven patients with visceral thrombosis resulting in extrahepatic non
      cirrhotic portal hypertension. RESULTS: Seven consecutive patients encountered
      over the past 19 years were observed for 78 patient-years, the first 14 patient
      years prior to anticoagulant therapy and the latter 64 patient-years on oral
      anticoagulant therapy. No patients rethrombosed either visceral or systemic
      vessels while on oral anticoagulant therapy. There were no fatal or serious
      hemorrhagic events on oral anticoagulant therapy; in fact, upper gastrointestinal
      bleeding decreased from 1.2 to 0.2 bleeds/year. The endoscopic grade of
      esophageal varices decreased in four of five patients who underwent serial
      endoscopy, and platelet counts increased in all seven patients. CONCLUSIONS:
      Chronic oral anticoagulant therapy is safe and not associated with an increase in
      upper gastrointestinal bleeding in such patients. Additionally, and by inference,
      perhaps in conjunction with the natural history of portal hypertension, such
      therapy is possibly effective in reducing portal hypertension in patients with
      hypercoagulability-induced extrahepatic portal hypertension.

PMID- 17221330
TI  - Tenecteplase to treat pulmonary embolism in the emergency department.
AB  - Tenecteplase, a mutant form of alteplase, possesses pharmacological properties
      that might favor its use for emergent fibrinolysis of acute pulmonary embolism.
      Contemporaneous search of the World's literature reveals 14 humans with acute
      pulmonary embolism treated with tenecteplase. Here, we summarize those cases and
      report the presentation features, dosing details and outcomes of eight additional
      patients with acute pulmonary embolism treated with tenecteplase in an academic
      emergency department. None of our eight patients had a significant hemorrhagic
      event after tenecteplase, and the outcomes of all eight appear to be acceptable.
      Taken together, we submit that the present case report and prior case reports are
      sufficient to comprise a phase I study of the safety and efficacy of tenecteplase
      to treat acute pulmonary embolism.

PMID- 17221332
TI  - Diagnostic and prognostic value of ambulatory ECG (Holter) monitoring in patients
      with coronary heart disease: a review.
AB  - Silent ischemia, the most common expression of atherosclerotic heart disease,
      affects approximately 30-50% of patients during their activities of daily living.
      The present review provides a comprehensive and practical summary of current
      knowledge on perioperative myocardial ischemia through MEDLINE searches up to
      June 2005, using keywords including "silent ischemia," "transient ischemia," and
      "Holter monitoring." Holter monitoring (i.e., continuous ambulatory ST-segment
      monitoring) is an effective tool for assessing the frequency and duration of
      silent transient myocardial ischemia, particularly in patients who are post-acute
      myocardial infarction (MI), those with acute coronary syndromes (ACS), and in
      patients in the acute post-operative period. Holter monitoring allows for further
      risk stratification of patients who have a positive exercise ECG by collecting
      long-term ECG data on ischemic and arrhythmic events while patients perform
      routine activities. Both the presence and increased duration of transient
      ischemia as detected by continuous ST-segment Holter monitoring are associated
      with increased rates of coronary events and mortality. Holter monitoring may aid
      in the identification of patients and subgroups of patients with ACS who may
      derive the greatest benefit from antiplatelet and antithrombotic therapy. Indeed,
      many ongoing and upcoming trials of pharmacotherapy include ischemia on Holter
      monitoring as an endpoint.

PMID- 17221333
TI  - Tissue factor and nitric oxide: a controversial relationship!
AB  - Tissue factor (TF) is the primary physiological initiator of blood coagulation.
      TF has a high-affinity for factor (F) VII resulting in the formation of
      (TF:FVII:FVIIa) bimolecular complex which, in the presence of Ca(2+), increases
      the enzymatic activity of FVIIa towards its natural substrates, FIX and FX,
      generating their active forms FIXa and FXa, respectively. This eventually leads
      to thrombin generation and a fibrin clot formation. Up-regulation of TF in
      injured blood vessels and atherosclerotic plaque can lead to undesirable vascular
      thrombosis. Nitric oxide (NO) is a free radical synthesized from L-arginine and
      molecular oxygen by nitric oxide synthases (NOS). NO participates in diverse
      physiological and pathophysiological process as an intra or extracellular
      messenger. A relationship between TF and NO has been proposed. Thus, models of TF
      regulation by NO has been studied in different cells and experimental animal
      models, but the results have been conflicting. The premise that NO donors can
      prevent TF expression in vivo has provided the foundation for a broad field of
      pharmacotherapeutics in vascular medicine. A new class of drugs combining a
      statin (inhibitors of coenzyme A reductase) with an NO-donating moiety has been
      described. The resulting drug, nitrostatin, has been suggested to increase the
      antithrombotic effects of native statin. However, it is questionable if NO
      release from these drugs had any significant role on TF inhibition. In summary,
      care must be taken in drawing conclusions about the relationship between NO and
      TF. Interpretation of NO studies must take several factors into consideration,
      including NO bioavailability, its half-life and inactivation, as well as the cell
      type and experimental model used.

PMID- 17221334
TI  - Epigenetic control of nuclear architecture.
AB  - The cell nucleus is a highly structured compartment where nuclear components are
      thought to localize in non-random positions. Correct positioning of large
      chromatin domains may have a direct impact on the localization of other nuclear
      components, and can therefore influence the global functionality of the nuclear
      compartment. DNA methylation of cytosine residues in CpG dinucleotides is a
      prominent epigenetic modification of the chromatin fiber. DNA methylation, in
      conjunction with the biochemical modification pattern of histone tails, is known
      to lock chromatin in a close and transcriptionally inactive conformation. The
      relationship between DNA methylation and large-scale organization of nuclear
      architecture, however, is poorly understood. Here we briefly summarize present
      concepts of nuclear architecture and current data supporting a link between DNA
      methylation and the maintenance of large-scale nuclear organization.

PMID- 17221338
TI  - Predictors of treatment outcome in headache patients with the Millon Clinical
      Multiaxial Inventory III (MCMI-III).
AB  - The objective was to discover possible psychological factors influencing
      treatment outcome for headache patients referred to psychological treatment in a
      tertiary headache centre by initial assessment using the Millon Clinical
      Multiaxial Inventory III (MCMI-III). The MCMI-III was administered to 136
      referred patients. Patients with valid protocols who had completed their
      treatment by October 2003 were included. Multidisciplinary treatment was offered
      including psychological treatment, mainly pain and stress management,
      pharmacological treatment and physiotherapy. Medians of MCMI-III scales for
      patients with and without reduction in headache frequency were compared. All of
      the eligible 58 patients were included in the study. Patients with reduction in
      headache frequency after treatment had lower scores on the MCMI-III Somatoform,
      Major depression and Avoidant personality pattern scales and higher scores on the
      Alcohol Dependence, Self-Defeating personality pattern, Depressive personality
      pattern, Drug Dependence, Aggressive personality pattern and Bipolar: Manic
      scales before treatment compared to patients without effect. Patients with a
      positive treatment effect reported less symptoms of depression and seemed less
      inclined to somatisation than non-responders. Responders also appeared more
      likely to experience increased social or occupational distress and report
      difficulties with handling emotions and an enduring tendency to focus on negative
      aspects of the self-image. The results can give valuable information regarding
      treatment planning and development.

PMID- 17221336
TI  - Treatment of autoimmune disease: time for a paradigm shift?
AB  - Current treatment of human autoimmune diseases (AIDs) was developed empirically
      and relies mostly on non-selective suppression of the immune system. Traditional
      non-selective immunosuppressants such as corticosteroids, cyclophosphamide, and
      methotrexate and more novel means such as monoclonal antibodies to CD3, CD4, or
      CD25 do not discriminate between pathogenic and beneficial T cells. Importantly,
      the severe side effects seen with current therapies are related to the fact that
      these treatments not only suppress the pathogenic disease-inducing cells, but
      also cells influential in combating infections and killing malignant cells.
      Severe infections and malignancies are the inevitable result of non-selective
      immune suppression. Many of the novel forms of therapy of AID were developed in
      experimental animals, and their translation to the human disease was associated
      with the revelation of unexpected and sometimes catastrophic side effects. These
      surprises underscore the major differences between the relative simplicity of the
      experimental model and the complexity of the human disease. How can this current
      state of treatment of AID be improved? Which principles should guide us in the
      design of new treatments? This review attempts to offer a new look at these
      questions.

PMID- 17221335
TI  - Expression of interleukin-16 by tumor-associated macrophages/activated microglia
      in high-grade astrocytic brain tumors.
AB  - INTRODUCTION: Macrophages/microglial cells are considered as immune cells in the
      central nervous system. Interleukin (IL)-16 is a proinflammatory cytokine
      produced by activated monocytic cells. MATERIALS AND METHODS: Expression of IL-16
      was analyzed by immunohistochemistry in human astrocytic brain tumors and the rat
      C6 glioblastoma tumor model. IL-16 was detected in both human astrocytic brain
      tumors and rat C6 glioma. RESULTS: Compared with human control brains, a
      significant increase in the percentages of parenchymal IL-16+
      macrophages/microglia was observed already in grade II astrocytomas, indicating
      that IL-16+ immunostaining could be a descriptor of a macrophage/microglia subset
      in astrocytic brain tumors. A further increase was observed at the transition
      from grade II to III astrocytomas. This increase in IL-16 immunoreactivity
      correlated with WHO grades of human astrocytic brain tumors. CONCLUSIONS:
      Therefore, IL-16 might be a so far unknown factor in the regulation of the local
      inflammatory milieu of human and experimental astrocytomas.

PMID- 17221339
TI  - Atypical primary headache responding to finger pressure: possible involvement of
      the vagus nerve?
AB  - We describe a case of atypical primary headache strongly responsive to prolonged
      pressure in the anterior aspect of the neck. We hypothesize that, at least in
      this case, the trigemino-cervical system and its connections with the vagus nerve
      are involved.

PMID- 17221340
TI  - Sumatriptan 6 mg subcutaneous as an effective migraine treatment in patients with
      cutaneous allodynia who historically fail to respond to oral triptans.
AB  - The objective of the study was to assess the efficacy of 6 mg subcutaneous (s.c.)
      sumatriptan to treat migraine and the relationship between response of migraine
      and cutaneous allodynia in a population of migraine patients who historically
      failed to respond to oral triptan medications. This was an open-label study
      consisting of patients with migraines who historically failed to respond to oral
      triptan medications. Forty-three patients were asked to treat three migraine
      attacks with 6 mg s.c. sumatriptan. The primary efficacy endpoint was the
      percentage of patients achieving relief of headache at 2 h. Ninety-one percent of
      the patients responded to a single dose of s.c. sumatriptan 6 mg. Fifty percent
      of all patients were pain-free by 2 h and over 30% had a 24-h sustained pain-free
      response. When administered within 90 min from the onset of migraine (i.e.,
      during the developing phase of cutaneous allodynia), s.c. 6 mg sumatriptan proved
      to be effective despite the occurrence of allodynia in a group of patients, who
      historically had failed to respond to oral triptan medications. These findings
      suggest that the window of opportunity to treat allodynic patients with
      injectable triptans may be longer (up to 2 h) than with oral triptans (up to 1
      h).

PMID- 17221341
TI  - Patent foramen ovale and migraine: no reason to intervene.

PMID- 17221337
TI  - Eicosanoid regulation of pulmonary innate immunity post-hematopoietic stem cell
      transplantation.
AB  - Hematopoietic stem cell transplantation (HSCT) is a therapeutic option for a
      number of malignant and inherited disorders. However, the efficacy of this
      therapy is limited by a number of serious infectious and noninfectious
      complications. Pulmonary infections represent a significant cause of morbidity
      and mortality post-HSCT and can occur both pre- and post-hematopoietic
      reconstitution. Susceptibility to Gram-negative bacterial infections despite full
      hematopoietic engraftment suggests that innate immunity remains impaired months
      to years post-HSCT. This review will describe the process and complications of
      HSCT and will summarize what is known about innate immune reconstitution post
      HSCT. Data from the literature as well as our own laboratory will be presented to
      suggest that an eicosanoid imbalance characterized by over-production of
      prostaglandins and under-production of leukotrienes leads to impaired lung
      phagocyte function post-HSCT. Of therapeutic interest, strategies which limit
      production of prostaglandins can improve pulmonary host defense in animal HSCT
      models, which suggests that this may also be beneficial for human HSCT
      recipients.

PMID- 17221344
TI  - Present and previous psychopathology of juvenile onset migraine: a pilot
      investigation by Child Behavior Checklist.
AB  - The objective was to describe the premorbid state of migraine with juvenile
      onset. Thirty subjects with migraine and 30 healthy subjects were enrolled in a
      case-control study. A structured questionnaire (Child Behavior Checklist, CBCL)
      was administered to the mothers and ratings were obtained for the past two age
      periods (0-3 and 4-6 years) and for the present state. CBCL scores of the
      migraine group (MG) were compared to those of the control group (CG) during the
      three periods. A longitudinal study was performed to evaluate the evolution of
      psychopathology comparing CBCL scores of MG in the three age periods. During the
      premorbid period MG showed significantly higher mean scores on total,
      internalising, anxious-depressive scales. In the longitudinal perspective,
      internalising traits were present in the premorbid period in MG. Children later
      diagnosed as having migraine differ from CG in several scales during different
      age periods. Migraine could be considered as the expression of a previous
      vulnerability.

PMID- 17221343
TI  - How many migraine patients need prolonged (>1 year) preventive treatment?
      Experience with topiramate.
AB  - The usual recommended duration of preventive treatment for migraine is 3-6
      months. Our aim was to explore how many patients attending a specialised clinic
      need prolonged preventive treatment for longer than one year. Eighty consecutive
      migraine patients who received preventive treatment with topiramate for 3 months
      with good response and tolerability were included in this observational study.
      All patients continued on topiramate until they had completed 6 months, when this
      drug was stopped. Topiramate was reintroduced if there was a worsening.
      Topiramate was kept for 6 more months and then discontinued again. Those patients
      whose headaches became worse after this second withdrawal received topiramate
      again and were followed-up for at least half a year. Headaches did not worsen
      after the first withdrawal at 6 months in 40 patients (50%), while they clearly
      worsened in the remaining 40 patients. At the end of the first year only two
      patients out of these 40 (5%) discontinued topiramate and did not notice an
      increase in headache frequency after two months. In conclusion, around half of
      the patients attending a specialised clinic due to frequent headache need
      preventive treatment for more than one year. Our data suggest that the current
      practice recommending periods of preventive treatment of 3-6 months should be
      reconsidered for many patients.

PMID- 17221342
TI  - Personality in patients with migraine evaluated with the "Temperament and
      Character Inventory".
AB  - The objective of this study was to assess the personality profile of a sample of
      Mexican patients with migraine using the Temperament and Character Inventory
      (TCI). A cross-sectional study was performed including adult migraine patients
      identified from the outpatient neurology clinics of two large teaching hospitals
      in Mexico City. Patients were asked to voluntarily participate in the study. A
      physician conducted a standardised diagnostic interview adhering to the criteria
      of the International Headache Society (IHS). Patients were interviewed and
      administered the TCI. We used two healthy controls groups and a third group of
      non-migraine pain controls. One hundred and fortytwo subjects with migraine, 108
      healthy blood donors, 269 young healthy controls and 30 patients with non
      migraine pain (NMP) were included in the study. Patients with migraine had higher
      scores in the dimension harm avoidance (HA) and all its sub-dimensions (p<0.05)
      than healthy patients. Patients with non-migraine pain had high scores in HA and
      low scores in novelty seeking, self-directedness and cooperativeness. Blood
      donors had high scores in the following subdimensions: HA1, HA4 and C3
      (Cooperativeness). Personality features consistent with migraine are avoidance,
      rigidity, reserve and obsessivity. Our study shows that patients with chronic
      pain share some of the personality features of patients with migraine but their
      TCI profile could be indicative of cluster C avoidant personality. Blood donors
      were shown to have more energy, with a tendency to help other people and be more
      optimistic. The results support serotoninergic involvement as explaining the
      physiopathology of migraine.

PMID- 17221346
TI  - [Polymorphisms of MICA microsatellites in thyroidal autoimmunity].
AB  - BACKGROUND: The autoimmune thyropathies Graves' disease (GD) and Hashimoto's
      thyroiditis (HT) have multiple genetic and environmental backgrounds. Allele
      alterations of immune genes might contribute to the development of autoimmunity.
      PATIENTS AND METHODS: This study determined a triplet short tandem repeat (STR)
      polymorphism in the transmembrane region of the major histocompatibility complex
      (MHC) class I chain-related gene A (MICA) of 391 subjects (129 patients with GD,
      56 patients with HT, and 206 healthy controls). Five common alleles have been
      reported for MICA. Genotypes were determined by fragment-length analysis in an
      ABI PRISM automatic sequencer. RESULTS: The prevalence of the MICA allele A9 was
      raised in patients with HT compared to controls (22.4% vs. 13.1%; p = 0.016;
      Fisher's exact test). For MICA, the genotype A5.1/A5.1 occurred more frequently
      in patients with GD than in controls (24.0% vs. 13.6%, odds ratio [OR] = 2.0, 95%
      confidence interval [95% CI] = 1.1-3.6; p = 0.018). The genotype MICA A6/A9 was
      decreased in patients with GD in contrast to controls (1.6% vs. 5.8%, OR = 0.2,
      95% CI = 0.6-1.2; p = 0.089). Also, in patients with HT, the genotype A5.1/A9 was
      increased compared to controls (23.2% vs. 10.7%, OR = 2.5, 95% CI = 1.2-5.4; p =
      0.025). CONCLUSION: The genotype MICA A5.1/A5.1 may be regarded as a risk factor
      for the development of GD. Also, the MICA genotype A5.1/A9 could raise the risk
      for acquiring HT. Finally, the genotype MICA A6/A9 could be seen as a protective
      factor against GD.

PMID- 17221345
TI  - The rare, unilateral headaches. Vaga study of headache epidemiology.
AB  - In the Vaga study of headache epidemiology, 1838 parishioners in the age group 18
      65 years were included (88.6% of the relevant population). Each individual was
      questioned in a face-to-face situation. In this population, a search of rare
      unilateral headaches was also made, in spite of their presumed rarity. Trigeminal
      neuralgia was present in two cases. Two individuals with SUNCT traits were
      observed. Hemicrania continua may have been present in one individual. Also
      observed were: optic neuritis (n=1), herpes zoster (n=4); a case of unilateral
      headache upon neck rotation (chronic paroxysmal hemicrania variant? or "forme
      fruste" of the neck-tongue syndrome?); masseter muscle spasm (n=1); temporo
      mandibular joint dislocation (n=1); and possible carotidynia (n=3). A
      particularly intriguing form of headache was a unilateral, neuralgiform (?) pain,
      associated with ipsilateral, regular jabs and allodynia, a combination observed
      in eight females. A couple of conditions that entirely defy rubrication are also
      reported.

PMID- 17221347
TI  - [Diagnosis of primary hyperaldosteronism].
AB  - Primary hyperaldosteronism is the most common secondary form of hypertension.
      Diagnosis of this entity is recommended in hypokalemic hypertension, in therapy
      resistant hypertension (at least three 3 drugs and RR > 140/90 mmHg), and in
      adrenal incidentalomas (= incidentally discovered adrenal tumors). For screening,
      the ratio between plasma aldosterone (PAC) and plasma renin concentration (PRC)
      should be measured. In the assessment of PAC/PRC ratio, the discontinuation of
      some antihypertensive medication and assay-specific cutoff values must be
      noticed. After a positive screening test, saline infusion test should be done as
      confirmatory test. In contraindications/impracticability of this test, 24-h urine
      collection for aldosterone-18-glucuronide under high-sodium diet can be used as
      alternative confirmatory test. After confirmation of primary hyperaldosteronism,
      differential diagnosis between aldosterone-producing adenoma and idiopathic
      hyperaldosteronism has to be done. For this approach, adrenal CT or MRT, posture
      test and adrenal vein catheterization as gold standard test are available.
      Whereas therapy of aldosterone-producing adenoma is surgery, idiopathic
      hyperaldosteronism is to be treated medically by spironolactone.

PMID- 17221349
TI  - [Drug-eluting or bare-metal stents in interventional cardiology. Theory and
      practice].
AB  - Drug-eluting stents (DES) reduce the restenosis rate after coronary
      interventions. They became the third milestone of interventional cardiology after
      coronary angioplasty and stent implantation. However, studies with hard endpoints
      showing a beneficial effect of DES are still missing. Recent metaanalyses are
      even suggesting a higher mortality in patients with DES. Now, before DES become
      avoided, exact indications and limitations have to be defined.

PMID- 17221348
TI  - [Fibromyalgia. Diagnostics--disease approach--therapy].
AB  - Fibromyalgia is a complex of symptoms predominantly affecting females and
      consisting of widespread pain. Etiology and pathogenesis are not sufficiently
      known yet, however, there is the assumption that fibromyalgia is looked at as
      being an illness with biological, psychological, and social aspects. Therefore,
      the treatment of fibromyalgia calls for a multimodal therapy approach. The
      importance of fibromyalgia has been recognized within the German health system by
      creating the new ICD code M79.70 and by assigning fibromyalgia its own
      rheumatologic DRG (I79Z). In future research of fibromyalgia special attention
      needs to be placed upon gender-specific problems.

PMID- 17221350
TI  - [Improvement of medical care by supporting the intention to change health risk
      behavior].
AB  - A large proportion of disease and death cases could be prevented, if efficacious
      programs, particularly concerning tobacco smoking, obesity, and alcohol risk
      drinking, could be applied. Feasible approaches are based, among others, on the
      Transtheoretical Model of intentional health behavior change. This model allows
      to develop practical approaches to reduce risk factors of common diseases at the
      general population level. Evidence about the promotion of the intention to change
      health risk behaviors revealed successes, e. g., according to smoking cessation.
      The effects are growing by time. Intervention that is focused at the promotion of
      change of health risk behaviors can add to the improvement of health care.

PMID- 17221351
TI  - [Main symptom jaundice--differential diagnosis at the bedside].
AB  - In jaundice, tissues are yellow in color because of an excessive deposition of
      bilirubin secondary to hyperbilirubinemia. Bilirubin is the physiological end
      product of heme metabolism. Jaundice is one of the main symptoms of hepatobiliary
      disease. Besides that, it might occur in the setting of cardiac, hematologic or
      pancreatic disorders. The onset of jaundice varies from acute with severe
      impairment of general condition to chronic and not being noticed by the patient
      at all. In the first part of this review, the physiological and
      pathophysiological molecular mechanisms of heme and bile metabolism are described
      in detail on a scientific basis. The knowledge of the main principles of heme
      degradation, canalicular bile secretion and enterohepatic cycling of bile salts
      helps to understand, why clinicians differentiate between prehepatic (hemolytic),
      hepatocellular and obstructive jaundice. A detailed patient's history and a
      careful physical examination are essential for the clinical differential
      diagnosis of jaundice. In combination with routinely obtained lab results, it is
      often possible to find the right diagnosis already at the bedside. To demonstrate
      this, the second part of this review sets the focus on the analysis of three case
      reports from the clinical point of view. The differential diagnosis of jaundice
      is summarized in a table.

PMID- 17221352
TI  - [The German Program for Disease Management Guidelines: COPD Guideline 2006. Short
      review].
AB  - In Germany, the first national consensus on evidence-based recommendations for
      COPD prevention and disease management was reached in spring 2006. After a
      development period of 9 months, the National Disease Management Guideline COPD
      was finalized by nominal group process under the authorship of the scientific
      societies for pneumology (DGP and Atemwegsliga), general internal medicine
      (DGIM), family medicine (DEGAM), and the Drug Commission of the German Medical
      Association (AKDAE). The recommendations' main sources are the NICE COPD
      Guideline 2004, the GOLD Recommendations as well as existing German guidelines
      and reviews of recent scientific evidence. The article gives an overview on
      authors, sources, and key recommendations of the German National Disease
      Management Guideline COPD 2006 (www.copd.versorgungsleitlinien.de).

PMID- 17221353
TI  - [Endocarditis due to Granulicatella adiacens].
AB  - CASE REPORT: A prosthetic aortic valve was implanted in a 41-year-old patient
      with connatal aortic stenosis. 14 months later a bacterial endocarditis was
      diagnosed and treated with ceftriaxone. 6 weeks later he had a relapse. Satellite
      streptococci could be cultivated from three blood cultures, later identified as
      Granulicatella adiacens. The patient was treated with penicillin and gentamicin.
      REVIEW OF THE LITERATURE: In a short review of the literature the most important
      aspects of pathogenesis, diagnostics and therapy of endocarditis due to satellite
      streptococci are presented.

PMID- 17221354
TI  - [Charcoal smoke causes bronchial anthracosis and COPD].
AB  - BACKGROUND: Bronchopulmonary disease due to inhalation of smoke from open
      woodfires represents a major health problem in developing countries. Due to
      increasing migration such patients also present to medical services in Europe.
      CASE REPORT AND DISCUSSION: An 84-year-old Afghan housewife who never smoked nor
      has a history of exposure to inorganic dusts, presents with chronic obstructive
      pulmonary disease (COPD) in association with bronchial anthracosis and stenosis
      of a bronchus. The complaints are found to be caused by chronic inhalation of
      smoke from an open woodfire which was used for cooking. The main complaints of
      "woodsmoke-associated lung disease" are cough und dyspnea with bronchial
      obstruction. Radiology and bronchoscopy usually reveal changes which are similar
      to pneumoconiosis of miners but without patients' relevant exposure. There is a
      frequent association of anthracotic bronchial stenosis and infection with
      tuberculosis. CONCLUSION: Since patients rarely recognize the risks of woodsmoke
      inhalation, they hardly report their exposure. Thus, the anamnesis is crucial to
      establish the right diagnosis and guide the patient to the appropriate diagnostic
      and therapeutic procedures.

PMID- 17221355
TI  - [False admission yes or no: who's right?].

PMID- 17221356
TI  - [Clinical assessment of potential fields of application of recombinant factor
      VIIa in internal and pediatric diseases. Recommendations of an expert group].
AB  - Recombinant factor VIIa (rFVIIa) is increasingly used outside the labeled
      indications for treatment of life-threatening bleeding episodes after failure of
      the respective standard therapy. An interdisciplinary group of experts summarizes
      the state of knowledge of the use of rFVIIa in gastroenterology and hepatology,
      thrombocytopenia and -pathia, coagulation factor deficiencies, von Willebrand's
      disease, periinterventional bleeding without specific bleeding diathesis, drug
      induced bleeding, disseminated intravascular coagulation, and neonatology. The
      most commonly used dose is 90 microg/kg body weight rFVIIa as bolus, if necessary
      followed by additional injections at intervals of 2-3 h. In factor VII deficiency
      lower dosages of 15-30 microg/kg body weight of rFVIIa are given every 4-6 h,
      whereas higher doses of 150-200 microg/kg body weight are used in neonates.

PMID- 17221357
TI  - Complete tear of ventral penile skin and penile urethra: a rare infective
      complication of chronic urethral catheterization.
AB  - We report the case of a 93-year-old paraplegic male patient who presented with
      complete tear of penile urethra and ventral penile skin due to indwelling
      urethral catheter. Therefore, debilitating patients with chronic indwelling
      urethral catheters should be in surveillance and caregivers of these patients
      should be alerted for such potential complications.

PMID- 17221358
TI  - Schistosoma-induced amyloidosis in hamsters is gender-dependent.
AB  - BACKGROUND: A high serum level of female protein (FP), found to be a constituent
      of Syrian hamster amyloid was associated with enhanced amyloidosis. In this work,
      we studied the sex-limited factors in the induction of amyloidosis in Syrian
      hamsters infected with either Schistosoma mansoni or S. hematobium cercariae.
      METHODS: Hamsters were infected with different species of schistosome cercariae
      and sacrificed after different time periods of infection. Kidney and liver
      specimens were processed in paraffin, stained with Congo-red and examined by
      ordinary light and polarized light microscopy. RESULTS: Statistical analysis
      showed a significant difference in intensity of kidney and liver amyloid deposits
      (P<0.002 & <0.007 respectively) between females and male hamsters with extensive
      deposits in the former. Amyloid deposits were correlated significantly to the
      duration of infection (P<0.001) than the load of worm recovered. CONCLUSION: From
      this study, we conclude that, in hamster model, Schistosoma-induced amyloidosis
      is enhanced in females than male hamsters. This may be due to the high serum
      level of FP that is normally detected in females. As an experimental model for
      schistosomal nephropathy, we recommend to use male hamsters instead of females to
      minimize the effect of amyloid deposits, which may mask other pathological
      changes associated with schistosomal infection.

PMID- 17221359
TI  - Putrescine N-methyltransferases--a structure-function analysis.
AB  - Putrescine N-methyltransferase (PMT) is a key enzyme of plant secondary
      metabolism at the start of the specific biosynthesis of nicotine, of tropane
      alkaloids, and of calystegines that are glycosidase inhibitors with nortropane
      structure. PMT is assumed to have developed from spermidine synthases (SPDS)
      participating in ubiquitous polyamine metabolism. In this study decisive
      differences between both enzyme families are elucidated. PMT sequences were known
      from four Solanaceae genera only, therefore additional eight PMT cDNA sequences
      were cloned from five Solanaceae and a Convolvulaceae. The encoded polypeptides
      displayed between 76% and 97% identity and typical amino acids different from
      plant spermidine synthase protein sequences. Heterologous expression of all
      enzymes proved catalytic activity exclusively as PMT and K (cat) values between
      0.16 s(-1) and 0.39 s(-1). The active site of PMT was initially inferred from a
      protein structure of spermidine synthase obtained by protein crystallisation.
      Those amino acids of the active site that were continuously different between
      PMTs and SPDS were mutated in one of the PMT sequences with the idea of changing
      PMT activity into spermidine synthase. Mutagenesis of active site residues
      unexpectedly resulted in a complete loss of catalytic activity. A protein model
      of PMT was based on the crystal structure of SPDS and suggests that overall
      protein folds are comparable. The respective cosubstrates S-adenosylmethionine
      and decarboxylated S-adenosylmethionine, however, appear to bind differentially
      to the active sites of both enzymes, and the substrate putrescine adopts a
      different position.

PMID- 17221362
TI  - Computerized cytomorphometric analysis of nuclear area, nuclear perimeter and
      mean nuclear diameter in spontaneous canine mammary gland tumours.
AB  - Fifty-two spontaneous canine mammary gland tumours (fibroadenomas (n=8),
      tubulopapillary carcinomas (n=9), solid carcinomas (n=6), anaplastic carcinomas
      (n=7), fibrosarcomas (n=9), liposarcomas (n=9) and osteosarcomas (n=4) were
      analysed by computer-assisted nuclear morphometry in Hemacolor-stained
      cytological specimens. Computerized cytomorphometry was performed and the nuclear
      area, nuclear perimeter and mean nuclear diameter of investigated tumours were
      assessed. A minimum of 100 nuclei per lesion were examined. The statistical
      analysis revealed statistically significant differences between benign and
      malignant neoplasms. The results indicated that computer-assisted nuclear
      morphometry could be used as an additional method for differentiation of benign
      from malignant canine mammary gland tumours in cytological specimens.

PMID- 17221361
TI  - Amplicon-plus targeting technology (APTT) for rapid production of a highly
      unstable vaccine protein in tobacco plants.
AB  - High-level expression of transgenes is essential for cost-effective production of
      valuable pharmaceutical proteins in plants. However, transgenic proteins often
      accumulate in plants at low levels. Low levels of protein accumulation can be
      caused by many factors including post-transcriptional gene silencing (PTGS)
      and/or rapid turnover of the transgenic proteins. We have developed an Amplicon
      plus Targeting Technology (APTT), by using novel combination of known techniques
      that appears to overcome both of these factors. By using this technology, we have
      successfully expressed the highly-labile L1 protein of canine oral papillomavirus
      (COPV L1) by infecting transgenic tobacco plants expressing a suppressor of post
      transcriptional gene silencing (PTGS) with a PVX amplicon carrying a gene
      encoding L1, and targeting the vaccine protein into the chloroplasts. Further, a
      scalable "wound-and-agrospray" inoculation method has been developed that will
      permit high-throughput Agrobacterium inoculation of Nicotiana tabacum, and a
      spray-only method (named "agrospray") for use with N. benthamiana to allow large
      scale application of this technology. The good yield and short interval from
      inoculation to harvest characteristic of APTT, combined with the potential for
      high-throughput achieved by use of the agrospray inoculation protocol, make this
      system a very promising technology for producing high value recombinant proteins,
      especially those known to be highly labile, in plants for a wide range of
      applications including producing vaccines against rapidly evolving pathogens and
      for the rapid response needed to meet bio-defense emergencies.

PMID- 17221360
TI  - The dsRNA-binding protein DRB4 interacts with the Dicer-like protein DCL4 in vivo
      and functions in the trans-acting siRNA pathway.
AB  - Arabidopsis thaliana encodes four Dicer-like (DCL) proteins and five dsRNA
      binding (DRB) proteins. We have previously demonstrated that DCL4 specifically
      interacts with DRB4 in vitro. Here we describe the interaction between DCL4 and
      DRB4 in vivo. The phenotype of a mutant with a defect in DCL4 (dcl4-2) was
      similar to that of a mutant with a defect in DRB4 (drb4-1): both mutant plants
      had elongated and downwardly curled rosette leaves and over-accumulated
      anthocyanin. In immunoprecipitation experiments with either anti-DCL4 or anti
      DRB4 antibody and crude extracts of wild-type Arabidopsis plants, co
      immunoprecipitation of DCL4 and DRB4 was detected, indicating that DCL4 interacts
      with DRB4 in vivo. This interaction was confirmed by immunoprecipitation
      experiments using extracts from dcl4-2, drb4-1, or transgenic plants expressing
      the hemagglutinin-tagged version of DCL4 or DRB4. The results of
      immunoprecipitation experiments also suggest that most DCL4 is associated with
      DRB4, but that some DRB4 is free or associated with other proteins. Reduced
      accumulation of the TAS1 and TAS3 trans-acting siRNA (ta-siRNA) and over
      accumulation of their target mRNAs (At5g18040 and auxin response factors ARF3 and
      ARF4) were detected in both drb4-1 and dcl4-2 mutants. These results indicate
      that DRB4, together with DCL4, functions in the ta-siRNA biogenesis.

PMID- 17221363
TI  - Elevated plasma levels of interleukin 1 beta, tumour necrosis factor alpha and
      monocyte chemotactic protein 1 are associated with pregnancy toxaemia in ewes.
AB  - Pregnancy toxaemia is a metabolic disorder that results from an inadequate energy
      supply to the growing maternal-fetal unit. The mechanism underlying the
      pathogenesis of the syndrome has not been fully clarified; however, a key role
      for cytokines and chemokines including interleukin 1 beta (IL-1 beta), tumour
      necrosis factor alpha (TNF-alpha) and monocyte chemotactic protein 1 (MCP-1) has
      been indicated in women and experimental animals. However, information on the
      maternal plasma levels of IL-1 beta, TNF-alpha and MCP-1 in ewes with pregnancy
      toxaemia is limited. Thus, the present study was designed to determine plasma IL
      1 beta, TNF-alpha and MCP-1 concentrations in ewes with severe (n=6) and mild
      (n=4) naturally occurring pregnancy toxaemia and in uncomplicated pregnant ewes
      (n=10) using enzyme-linked immunosorbent assay (ELISA). All ewes with pregnancy
      toxaemia had significantly lower body temperature and respiratory rate than
      uncomplicated pregnant ewes (p<0.05). With the highest concentrations in severe
      cases, heart rate, proteinuria and serum uric acid levels as well as plasma IL-1
      beta, TNF-alpha and MCP-1 were significantly different among all three groups
      (p<0.05). The plasma concentrations of IL-1 beta in control ewes and ewes with
      mild and severe toxaemia were 15.81 +/- 3.90 pg/ml, 23.83 +/- 2.42 pg/ml and
      34.55 +/- 8.03 pg/ml, respectively. The plasma concentrations of TNF-alpha in
      control ewes and ewes with mild and severe toxaemia were 7.71 +/- 1.61 pg/ml,
      16.13 +/- 3.63 pg/ml, and 22.85 +/- 3.64 pg/ml, respectively. The plasma
      concentrations of MCP-1 in control ewes and ewes with mild and severe toxaemia
      were 101.70 +/- 9.86 pg/ml, 134.75 +/- 6.24 pg/ml, and 157.67 +/- 9.69 pg/ml,
      respectively. Moreover, plasma IL-1 beta, TNF-alpha and MCP-1 levels were
      positively correlated with clinical and well-establish biochemical parameters of
      pregnancy toxaemia, serum uric acid and proteinuria (p<0.01). Concomitant
      increase of plasma IL-1 beta, TNF-alpha and MCP-1 concentrations along with serum
      uric acid, proteinuria, and worsening of the clinical signs indicates that such
      cytokines are involved in the aetiopathogenesis and in perpetuation of the local
      and systemic inflammatory reactions in pregnancy toxaemia in ewes. Hence, plasma
      IL-1 beta, TNF-alpha and MCP-1 may potentially serve as markers to monitor
      prognosis of pregnancy toxaemia in ewes.

PMID- 17221365
TI  - Cloning and sequence analysis of the gene encoding LipL32 of Leptospira
      interrogans serovar Sejroe.
AB  - Leptospira, a member of the order Spirochaetales, is the causative agent of
      leptospirosis, an important zoonosis encountered worldwide. The Leptospira
      interrogans serovar Sejroe was grown in EMJH medium and its DNA was isolated
      using standard techniques. The LipL32 gene was amplified using the reported
      primer of Kirschneri of LipL32. The amplified product was found to comprise 756
      base pairs. This amplified gene fragment of LipL32 lipoprotein was cloned in E.
      coli (DH5 alpha) cells using pDrive plasmid as a vector. The recombinant cells
      were selected on LB agar medium containing ampicillin, X-gal and isopropyl-beta-D
      thiogalactopyranoside. Plasmid was extracted from the recombinant white colonies,
      and restriction endonuclease (RE) analysis was carried out using PstI and SalI.
      On partial sequence analysis, the product exhibited 756 base pairs, corresponding
      to 251 amino acids. The cloned gene could be further used for expression of
      recombinant protein for serodiagnosis of leptospirosis.

PMID- 17221364
TI  - Cloning and sequencing of a 21 kDa outer membrane protein gene of Leptospira
      interrogans serovar Canicola strain Hond Utrecht IV.

PMID- 17221368
TI  - Recent developments in the isolation and structure elucidation of naturally
      occurring iridoid compounds.
AB  - Naturally occurring iridoid compounds are widely distributed in sympetalous
      plants and they serve as important taxonomic markers. In this survey their
      classification is given from the biosynthetic point of view. The recent
      literature concerning isolation and structure elucidation is reviewed, data on
      chromatography and spectroscopy, new types of iridoids and secoiridoids as well
      as new sugar moieties as constituents of iridoid glycosides are presented.

PMID- 17221366
TI  - The effects of salivary gland extracts from Boophilus microplus ticks on mitogen
      stimulated bovine lymphocytes.
AB  - The effect of salivary gland extract (SGE) from the tick Boophilus microplus was
      examined in mitogen-stimulated lymphocytes in vitro. SGE was added to lymphocytes
      of seven cattle together with the mitogens concanavalin A (ConA),
      phytohaemagglutinin (PHA) and pokeweed mitogen (PWM). Semi-purified B cells from
      another seven cattle were stimulated with the mitogen lipopolysaccharide (LPS).
      PHA and ConA stimulated proliferation of lymphocytes to the same extent, but the
      inhibition due to SGE of Boophilus microplus on the proliferative response
      stimulated by PHA (39.0% +/- 9.3%) was less than the inhibition of proliferative
      response stimulated by ConA (75.4% +/- 6.9%). In contrast, SGE of B. microplus
      stimulated the proliferation of B cells in the presence of LPS in a dose
      dependent manner. Enhanced stimulation of B cells by SGE at >4 microg in culture
      was greater than twice that observed when B cells were stimulated by LPS alone.
      SGE does not have a direct suppressive effect on bovine B cell proliferation;
      however, in vivo the effectiveness of B cell responses might be influenced by
      other immune factors, such as cytokine profiles.

PMID- 17221369
TI  - Anti-inflammatory activity of ginsenoside ro.
AB  - Ginsenoside Ro, an oleanane-type saponin has been screened for activity in
      experimental models of inflammation. Ginsenoside Ro (10,50, and 200 mg/kg, P. O.)
      inhibited an increase in vascular permeability in mice induced by acetic acid and
      reduced an acute paw edema in rats induced by compound 48/80 or carrageenin.
      Ginsenoside Ro did not suppress a developing adjuvant-induced edema in arthritic
      rats. However, ginsenoside Ro was found to be effective in hypercoagulable state,
      increase of connective tissue in the artery and calcium effluence from the bone
      in adjuvant-induced arthritic rats.

PMID- 17221370
TI  - Formation of Digitalis lanata Clone Lines by Shoot Tip Culture.
AB  - Propagation of DIGITALIS LANATA by shoot tip culture made possible (a) the rapid
      multiplication of elite plants with the formation of plant clones and (b) the
      long-term cultivation of these plants which under normal growth conditions would
      die at the end of the second vegetation period. Optimum conditions were
      established for the regeneration of shoots from shoot tips, for daughter shoot
      formation and rooting as well as for the adaptation of the regenerated plants to
      the open ground. Gene banks of valuable clones were built by keeping shoots at 4
      degrees C on media with high sucrose concentration (maximum period of storage 2
      years) or by growing juvenile clone plants in the greenhouse at temperatures
      preventing the induction of flowering. The clone plants were in the juvenile
      state even if they were derived from flowering mother plants. They showed normal
      growth and development.

PMID- 17221371
TI  - Cytostatic and antibacterial activity of some compounds isolated from several
      lamiaceae species from the canary islands.
AB  - A chemotherapeutic study has been carried out on thirteen products Eeleven
      diterpenes, one lignan, (+)-sesamin, and a coumarin, siderin] isolated from
      SALVIA and SIDERITIS species considered endemic to the Canarian flora. The data
      obtained suggest that some diterpenoid compounds show an interesting cytostatic
      activity, specially galdosol ( 6) with an ID (50) value of 0.5 microg/ml. These
      compounds also evidence a moderate antibacterial activity against Gram positive
      bacteria.

PMID- 17221372
TI  - New Diterpenoids from the Roots of Salvia triloba.
AB  - Eight diterpenoids, trilobinol ( 1), trilobinone ( 2), ferruginol, horminone,
      7alpha-acetylroyleanone, 6beta-hydroxyroyleanone, virgatol and cryptanol were
      isolated from the roots of SALVIA TRILOBA L. fil. (Labiatae); Trilobinol and
      trilobinone are new compounds, their structures were established by spectral
      methods.

PMID- 17221373
TI  - Tricyclic Diterpenes from the Stem Bark of Azadirachta indica.
AB  - Two new diterpenoids, margosone and margosolone, have been isolated from the stem
      bark of AZADIRACHTA INDICA A. Juss (neem) and their structures established as
      12,13-dihydroxy-14-isoporpylpodocarpa-8,11,13-trien-7-one and 13-hydroxy-12
      methoxypodocarpa-8,11,13-trien-7-one, respectively, through chemical and
      spectroscopic studies.

PMID- 17221374
TI  - Trijuganone A and B: Two New Phenanthrenequinones from Roots of Salvia trijuga.
AB  - To new phenynthrenequinone diterpenoids, trijuganone A and B, were isolated from
      the roots of SALVIA TRIJUGA Diels (Labiatae). Their chemical structures have been
      established by spectral analysis.

PMID- 17221375
TI  - Lignans and other constituents from South and central american zanthoxylum
      species.
AB  - Eight lignans (+/-)-syringaresinol, (-)-pinoresinol, (+)-sesamin, (+)-eudesmin,
      (+)-epieudesmin, (-)-asarinin, (-)-matairesinol, (-)-kobusin, two terpenes
      lupeol, beta-sitosterol, one aliphatic unsaturated amide, hydroxy-gamma-sanshool,
      and one alkaloid, magnoflorine, were isolated from ZANTHOXYLUM species of Central
      and South America. Their structures were elucidated mainly by (1)H-, (13)C-NMR,
      and mass spectroscopy.

PMID- 17221376
TI  - Triterpenoid Saponins from Anemone flaccida.
AB  - From the rhizome of ANEMONE FLACCIDA Fr. Schmidt, used in Chinese folk medicine,
      four saponins of oleanolic acid-A,B,C,D were isolated. By means of spectroscopy
      and chemical transformation, saponins A, B, and D were identified as 3- O-[alpha-
      L-rhamnopyranosyl-(1-->2)-alpha- L-arabinopyrasyl]-oleanolic acid, 3- O-[alpha- L
      rhamnopyranosyl-(1-->2)-beta- D-xylopyranosyl]-oleanolic acid, and 3- O-[alpha- L
      rhamnopyranosyl-(1-->2)-beta- D-glucopyranosyl]-oleanolic acid. These three
      saponins are known compounds but isolated from ANEMONE plants for the first time.
      Saponin C was elucidated as 3- O-[beta- D-glucopyranosyl-(1-->2)-beta- D
      xylopyranosy1]-oleanolic acid, which has not been reported in the literature
      before, and is named as flaccidoside I.

PMID- 17221377
TI  - Triterpenoid Saponins from Primula denticulata.
AB  - Two triterpene glycosides denticin ( 1) and denticulatin ( 2) have been isolated
      from the whole plant of PRIMULA DENTICULATA Sm. and their structures were
      established by spectral and chemical studies as 3beta-{ O-beta- D-glucopyranosyl
      (1-->4)-[ O-beta- D-xylopyranosyl-(1-->2)]- O-(beta- D-glucopyranosyl-(1-->4)-[ O
      beta- D-glucopyranosyl-(1-->2)]-alpha- L-arabinopyranosyloxy}-16alpha-hydroxy
      13beta, 28-epoxyolean-30-al and 3beta-{ O-beta- D-glucopyranosyl-(1-->2)- O-beta-
      D-glucopyranosyl-(1-->4)-[ O-beta- D-xylopyranosyl-(1-->2)]- O-beta- D
      glucopyranosyl-(1-->4)-[ O-beta- D-glucopyranosyl-(1-->2)]-alpha-L
      arabinopyranosyloxy}-16alpha-hydroxy-13beta,28-epoxyolean-30-al, respectively.

PMID- 17221378
TI  - Structure of Tripterygic Acid A: A New Triterpene of Tripterygium wilfordii.
AB  - From roots of TRIPTERYGIUM WILFORDII used in Chinese folk medicine, a new ursane
      triterpene named tripterygic acid A was isolated along with a known triterpene
      and their structures were elucidated by means of spectral analysis and chemical
      transformation.

PMID- 17221379
TI  - A Secoiridoid Glucoside from Gentiana scabra var. buergeri.
AB  - A new bitter acylsecoiridoid glucoside, rindoside, has been isolated along with a
      known iridoid glucoside, loganic acid, from rhizomes and roots of GENTIANA SCABRA
      var. BUERGERI. The structure of rindoside was established by chemical and
      spectral evidence.

PMID- 17221380
TI  - [Germacranolides, Guaianolides, and Xanthanolides from the Flowers of Arnica
      mollis and an X-Ray Structure Analysis of Baileyin Acetate].
AB  - The flowers of ARNICA MOLLIS afforded, in addition to baileyin ( 1A), baileyin
      acetate ( 1B), xanthalongin ( 3), and 2-deacetoxy-11alpha,13-dihydroxanthuminol (
      6), the new 1,5- CIS-guaianolides arnimollin acetate ( 2A) and arnimollin
      tiglinate ( 2A) and the new xanthanolides 11beta3,13-dihydroxanthalongin ( 4) and
      11alpha,13-dihydroxanthalongin ( 5). No traces of helenanolides were discernible.
      The structures were elucidated mainly by high-field NMR spectroscopy. The
      stereochemistry of 1B has been revised on the basis of an X-ray crystallographic
      study to be a 4alpha,5beta-epoxygermacrolide instead of a 4alpha,5beta
      epoxymelampolide. The implications for the biosynthesis of CIS- and TRANS-fused
      guaianolides are discussed. The co-occurrence of 1A with CIS-fused guaianolides
      and xanthanolides (no helenanolides) in A. MOLLIS and with TRANS-fused
      guaianolides and helenanolides (no xanthanolides) in A. ACAULIS supports the
      hypothesis that germacrolides represent the biogenetic precursors for CIS- and
      TRANS- fused guaianolides.

PMID- 17221381
TI  - [Further Helenanolides from the Flowers of Arnica chamissonis subsp. foliosa].
AB  - A phytochemical study of the flowers of ARNICA CHAMISSONIS Less. subsp. FOLIOSA
      (Nutt.) Maguire (Asteraceae) has resulted in the identification of a further 23
      helenanolides. Six of them, 2alpha-hydroxy-6- O-angelicoyl-2,3-dihydrohelenalin (
      3B), 2alpha-hydroxy-6- O-senecioyl-2, 3-dihydrohelenalin ( 3C), 2alpha-hydroxy-6-
      O-tigloyl-2,3,11alpha,13-tetrahydrohelenalin ( 4A), 2alpha-hydroxy-6- O
      isovaleryl-2, 3,11alpha,13-tetrahydrohelenalin ( 4D), 6- O-acetylchamissonolide (
      5C), and 4,6-di- O-acetylchamissonolide ( 5D), were isolated for the first time
      as natural compounds. Their structures were established by GLC-MS studies and IR,
      (1)H- and (13)C-NMR spectroscopy.

PMID- 17221383
TI  - Two Phenol Compounds from Berchemia racemosa.

PMID- 17221382
TI  - [Alkaline Cleavage of Polymeric Phenols from Sargassum muticum and Pelvetia
      canaliculata].
AB  - Low-molecular phenolic cleavage products as well as dibenzofurans are obtained by
      treatment of polymeric polyphenols from SARGASSUM MUTICUM and PELVETIA
      CANALICULATA (brown algae) with hot aqueous alkali. Similar degradation products
      were observed in the analogous treatment of model substances (1). Statements
      about certain structure elements of polymeric material can now be made from rules
      derived at that time. The polyphenol fraction from S. MUTICUM seems to contain
      only phlorotannins of the fuhalol type and those from P. CANALICULATA, in
      addition to a large portion of non-cleavable substances, several compounds of the
      fucophlorethol type.

PMID- 17221384
TI  - [Flavonoid Aglycones from Flowers of Heterotheca inuloides].

PMID- 17221385
TI  - Narcissus nivalis: A New Source of Galanthamine1.

PMID- 17221386
TI  - Secologanin and Derivatives from Gentiana verna.

PMID- 17221387
TI  - Xanthone Derivatives from Polygala nitida.

PMID- 17221388
TI  - The Essential Oil of Magnolia officinalis.

PMID- 17221389
TI  - Clonal Propagation of Atractylodes japonica and A. ovata by Tip Tissue Culture
      and the Atractylon Content of Clonally Propagated Plants.

PMID- 17221390
TI  - Structures of glycosides of bai-hua quan-hu1.

PMID- 17221391
TI  - Alkaloids of Strychnos ignatii.

PMID- 17221392
TI  - A Further Contribution to the gamma-Pyrone Constituents of Ammi visnaga Fruits.

PMID- 17221393
TI  - Batch Cultures of Somatic Embryos of Digitalis lanata in Gaslift Fermenters.
      Development and Cardenolide Accumulation.
AB  - Somatic embryos of DIGITALIS LANATA STRAIN VII were successfully grown as batch
      cultures in gaslift fermenters. Embryo development and formation of cardenolides
      in the embryos resembled those of cultures grown in shake flasks. Both processes
      depended on the developmental stage of the embryos at the time point of
      inoculation, the homogeneity of the embryo structures, the density of the
      inoculum, the composition of the nutrient medium, the intensity of irradiation,
      and the composition of the gas mixtures used for agitation of the embryo
      suspension. The cultures contained 0.7&-1.0 (micro,mol digitoxin equivalents g (
      1) dry wt. (2.6-6.5 micromol digitoxin equivalents l (-1)) after a cultivation
      period of 28 d.

PMID- 17221394
TI  - On the accumulation of apigenin in chamomile flowers.
AB  - By preparing and analysing extracts of fresh chamomile flowers from outdoor and
      greenhouse cultures, it was possible to show that apigenin does not actually
      occur in living chamomile flowers. Apigenin is the result of post-harvest
      processes converting apigenin 7-glycoside and its derivatives into the aglycone.
      The different apigenin/apigenin 7-glycoside ratios reported in the literature for
      various chamomile samples can easily be explained as the result of different post
      harvest conditions. The accumulation of free apigenin in chamomile flowers must
      be ascribed to the enzymatic degradation of apigenin 7-glycoside and other
      glycosidic derivatives of apigenin. Thus, the selection of chamomile types
      yielding large amounts of apigenin seems to be based on a degradation product.

PMID- 17221395
TI  - Bufadienolides from Urginea pancration.
AB  - From bulbs of URGINEA PANCRATION (Steinh.) G. de Philippe (Hyacinthaceae) 5
      bufadienolides were isolated by a combination of column and droplet counter
      current chromatography; their structures were elucidated mainly by FAB-MS and
      (1)H- and (13)C-NMR spectroscopy. Besides the already known scilliglaucoside (
      1), scillirubroside ( 2), and scilliroside ( 3), two new bufadienolides were
      identified: 5alpha-4,5-dihydroscillirosidin- 3beta- O-alpha- L-thevetosido-4'
      beta- D-glucopyranoside and arenobufagin-3beta- O- L-rhamnopyranosido-4'-beta- D
      glucopyranoside.

PMID- 17221396
TI  - Products of Allicin Transformation: Ajoenes and Dithiins, Characterization and
      their Determination by HPLC*.
AB  - Constituents of crushed garlic bulbs ( ALLIUM SATIVUM L.), such as allicin, (
      E/Z)-ajoene, and the vinyldithiins, were synthesized and purified by an LC
      method. Purity was proved by TLC, HPLC, and GC systems. Identity was confirmed by
      comparison with spectral data from the literature. In order to establish external
      standards, silica gel adsorbates of the respective substances were prepared. For
      quantitative determination of allicin and its transformation products, an
      isocratic HPLC method was developed. Calibration was performed by the use of
      these external standards, and by comparison to an internal standard. The
      influence of different media on allicin transformation, including the ( E/Z)
      ratio of the ajoenes, has been elaborated.

PMID- 17221397
TI  - New Polyindolenine Alkaloids from Calycodendron milnei.
AB  - Four new alkaloids, representing the first members of new groups of polyindolinic
      alkaloids, have been isolated from the aerial parts of CALYCODENDRON MILNEI along
      with other alkaloids. The names vatine, its stereoisomer vatine A, vatamine, and
      vatamidine are proposed. They are polymers of six, seven, and eight N(b)
      methyltryptamine units, respectively.

PMID- 17221398
TI  - New Canthin-6-one Alkaloids from Quassia amara.
AB  - From the wood of QUASSIA AMARA L. (Simarubaceae) two new canthin-6-one alkaloids
      have been isolated and their structures determined as 3-methyl-4-methoxy-5
      hydroxycanthin-2,6-dione ( 1) and 4-methoxy-5-hydroxycanthin-6-one 3-, N-oxide (
      2) by spectroscopic and chemical methods. 3-Methylcanthin-5,6-dione ( 3) has been
      also isolated and identified for the first time from this source.

PMID- 17221399
TI  - Steroidal Sapogenins from Tacca leontopetaloides.
AB  - Diosgenin and its ring-F-hydroxylated derivatives isonarthogenin {spirost-5-ene
      3,27-diol {3beta, 22 R, 25 S)} and isonuatigenin {spirost-5-ene-3,25-diol (3beta,
      22 R, 25 S)}, together with the 22,25-epoxyfurost-5-ene isomer nuatigenin {furost
      5-ene-3,26-diol-22,25-epoxy (3beta, 22 R, 25 S)}, were identified as the major
      steroidal sapogenins of the acid hydrolysate of an extract of leaves of TACCA
      LEONTOPETALOIDES by IR, (1)H-NMR, (13)C-NMR, and mass spectroscopy. A diosgenin
      ester was isolated which apparently arose by ring closure of a glycosylated
      furostene during hydrolysis.

PMID- 17221400
TI  - Analysis of the Essential Oil of Solidago canadensis.
AB  - The analysis of the volatile compounds in the essential oil of SOLIDAGO
      CANADENSISL. sensu lato (Compositae) GC and GC-MS demonstrated the presence of at
      least 36 compounds, 18 of which were identified. The Major comonenets are gamma
      (2)- and delta-cadinenes.

PMID- 17221401
TI  - The Essential Oil of Poliomintha incana.
AB  - The essential oil content and composition of freshly gathered POLIOMINTHA INCANA
      (Torr.), A. Gray (Labiatae) have been determined using analytical-scale capillary
      GC, preparative-scale packed column GC, GC/ MS, (1)H-NMR, and (13)C-NMR
      techniques. A relatively high yield of volatiles (2.6% of the dried plant) was
      isolated. The primary component of the oil is pulegone (77%). Other important
      constituents are 1,8-cineole (3.9%), linalool (3.4%), isopulegone (2.3%), alpha
      terpineol (2.0%), and 8-hydroxy-4- P-menthen-3-one (1.4%).

PMID- 17221402
TI  - Myrianthiphyllin, The First Lignan Cinnamate from Myrianthus arboreus.
AB  - Studies of the methylated ethyl acetate extract of the trunk wood of MYRIANTHUS
      ARBOREUS (Cec-ropiaceae) have resulted in the isolation of five known pentacyclic
      triterpenes and a new lignan cinnamate. The structural elucidation of the new
      compound has been effected on grounds of the interpretation of spectroscopic data
      and alkaline hydrolysis.

PMID- 17221403
TI  - Umbelliferose from Cachrys ferulacea Seeds: Determination of the Sugar Sequence
      by NMR 2D-COLOC Technique.
AB  - Umbelliferose has been isolated from the fruits of CACHRYS FERULACEA (L.)
      Calestani and the sugar sequence has been determined by NMR spectroscopic 2D
      COLOC technique. The method of identification of the trisaccharide, which occurs
      only in the Umbelliferae family and may have a chemotaxonomic significance, is
      described and briefly discussed.

PMID- 17221404
TI  - The Volatile Constituents of Calamintha grandiflora.

PMID- 17221405
TI  - Two New Eudesmanolides from Artemisia caerulescens subsp. gargantae.

PMID- 17221406
TI  - (-)-Fargesol, A New Lignan from the Flowers Buds of Magnolia fargesii.

PMID- 17221407
TI  - Chemical Features and Productivity of a Geraniol-Rich Variety (GRL-1) of
      Cymbopogon flexuosus*.

PMID- 17221408
TI  - Canthin-6-one Alkaloids from Pierreodendron africanum Stem Barks.

PMID- 17221409
TI  - Triterpenes from Sebastiania schottiana.

PMID- 17221410
TI  - Triterpenoids of Salvia longystyla1.

PMID- 17221411
TI  - 7-Methylphyscion and Cassiamin A from the Root Bark of Cassia singueana.

PMID- 17221412
TI  - Toxic Sesquiterpenoid Lactones from the Leaves of Coriaria microphylla.

PMID- 17221414
TI  - Terminology concerning garlic research.

PMID- 17221413
TI  - Isolation of Phaeanthine from Cyclea burmanni.

PMID- 17221415
TI  - A review of "Lexikon der Zauberpflanzen" by Christian Ratsch.

PMID- 17221416
TI  - Glaucolide B, A Molluscicidal Sesquiterpene Lactone, and Other Constituents of
      Vernonia eremophila.
AB  - The sesquiterpene lactone glaucolide B was isolated from the molluscicidal
      extract of VERNONIA EREMOPHILA Mart, and shown to be responsible for the
      molluscicidal activity. Hydrogenolysis of glaucolide B resulted in the
      disappearance of the activity. Other inactive constituents of the extract were
      3,7-dimethoxy-5,3',4'-trihydroxyflavone and two transformation products, possibly
      artefacts, of glaucolide B. Glaucolide B exhibited strong antimicrobial activity
      against B, CEREUS and moderate activity against S. AURENS, but was inactive in
      several other systems.

PMID- 17221417
TI  - [New Prenylflavonoid Glycosides from Epimedium koreanum].
AB  - Two new prenylflavonol glycosides epimedokoreanoside I ( 7) and
      epimedokoreanoside II ( 8) were isolated from EPIMEDIUM KOREANUM Nakai
      (Berberidaceae) beside five other known prenylflavonol glycosides with
      hypotensive activity. The structures were elucidated by spectroscopic and
      chemical methods.

PMID- 17221418
TI  - Structure Elucidation of Inflexarabdonins G and H: Two New Diterpenoids from
      Rabdosia inflexa.
AB  - From the dried aerial parts of RABDOSIA INFLEXA, two new diterpenoids, named
      inflexarabdonin G and inflexarabdonin H were isolated and the structures were
      elucidated as ENT-1beta,3alpha,11alpha-trihydroxy-kaur-16-en-15-one 3,11
      diacetate and ENT-1beta,3alpha,11alpha-trihydroxy-kaur-16-ene-6,15-dione 1,3
      diacetate, respectively, on the basis of spectroscopic and chemical evidence.

PMID- 17221419
TI  - [Acinospesigenin: A New Triterpene from the Leaves of Phytolacca acinosa].
AB  - The investigation of the hydrolysed aqueous methanolic extract from the leaves of
      PHYTOLACCA ACINOSA Roxb. resulted in the isolation of phytolaccagenin ( 1)
      besides a new pentacyclic triterpenoid which was identified as 2beta,3beta
      dihydroxy-23,30-dimethoxycarbonyl-28-carboxy-olean-12-ene = acinospesigenin ( 2).

PMID- 17221420
TI  - Further Triterpenoids of Musanga cecropioides: The Structure of Cecropic Acid.
AB  - Six pentacyclic triterpenic acid methyl esters have been isolated from the
      methylated ethyl acetate extract of the trunk wood of MUSANGA CECROPIOIDES, as
      well as a triterpene saponin of the same group. One of them, cecropic acid methyl
      ester, is new. The structures of these compounds have been established from
      interpretation of spectral data or chemical transformations. The known
      triterpenes include euscaphic and tormentic acid methyl esters, already isolated
      from the root wood of the plant, methyl cecropiaceate, and methyl pomolate,
      already obtained from the stem bark, and methyl arjunolate and beta- D-glucosyl
      tormentate, encounted in this plant for the first time.

PMID- 17221421
TI  - Triterpenoidal Constituents of Diploclisia glaucescens.
AB  - The pentacyclic triterpenoids serjanic acid and phytolaccagenic acid as well as a
      new glycoside, 3- O-beta- D-glucopyranosylphytolaccagenic acid have been isolated
      from the stem of DIPLOCLISIA GLAUCESCENS (Bl.) Diels (Menispermaceae). New
      spectroscopic data are furnished for serjanic acid and phytolaccagenic acid.

PMID- 17221422
TI  - New Taxanes from Taxus chinensis.
AB  - Two new taxane diterpenes, decinnamoyltaxagifine ( 3) and decinnanioyltaxagifine
      acetate ( 2), have been isolated from the leaves and stems of TAXUS CHINENSIS.
      Their structures were elucidated by spectroscopic methods. Their (13)C-NMR
      chemical shifts were assigned.

PMID- 17221423
TI  - Ambrosanolides and other constituents of two rudbeckia species.
AB  - Aerial parts of RUDBECKIA SUBTOMENTOSA Pursh furnished four C-15 functionalized
      ambrosanolides, one of them new, as well as coumarin. Aerial parts of RUDBECKIA
      TRILOBA L. var. TRILOBA furnished coumarin and two closely related
      thiopheneacetylenes.

PMID- 17221424
TI  - A New Minor Saponin from the Leaves of Panax ginseng.
AB  - Seventeen compounds were isolated from the leaves of PANAX GINSENG C. A. Meyer.
      Among them, a new minor saponin was established as 3beta,6alpha,12beta-trihydroxy
      dammar-20(22), 24-diene-6- O-alpha- L-rhamno-pyranosyl-(1-->2)-beta- D
      glucopyranoside ( 2). Fourteen compounds were identified as 20( R)
      protopanaxadiol ( 1), 20( R)-protopanaxatriol, ginsenoside-Rh (3), 20( R)
      ginsenoside-Rh (2), 20( S)-ginsenoside-Rh (2), ginsenoside-Rh (1), -Rg (3), -Rg
      (2), -Rg (1), -Re, -Rd, -Rc, -Rb (2), -Rb (1); the others are still under
      investigation.

PMID- 17221425
TI  - New Coumarins from Pilocarpus goudotianus.
AB  - The leaves of PILOCARPUS GOUDOTIANUS afforded in addition to eight known
      coumarins three new ones, donatin, alloxanthoxyletol, and (+)-elisin. The
      structures were elucidated on the basis of spectroscopic evidence and chemical
      derivatives.

PMID- 17221426
TI  - Structures of Angular Pyranocoumarins of Bai-Hua Qian-Hu, the Root of Peucedanum
      praeruptorum1.
AB  - Three new angular-type dihydropyranocoumarins, peucedanocoumarin I ( 1),
      peucedanocou-marin II ( 2), peucedanocoumarin III ( 3), and a known coumarin
      having the same skeleton, pteryxin ( 4), were isolated from the crude drug "Bai
      Hua Qian-Hu" of the Q-II type series, which is the root of PEUCEDANUM
      PRAERUPTORUM Dunn. (Umbelliferae). The chemical structures of 1, 2, and 3 have
      been established by physicochemical methods to be 3' ( S)-2-methylbutyryloxy-4'-(
      R)-acetoxy-3',4'-dihydroseselin, 3'( S)-acetoxy-4'( R)-angeloyloxy-3',4'
      dihydroseselin, and 3'( S)-acetoxy-4'( R)-tigloyloxy-3',4'-dihydroseselin,
      respectively.

PMID- 17221427
TI  - [The Relative Configuration of Acetogenins Isolated from Annona squamosa: Annonin
      I (Squamocin) and Annonin VI].
AB  - Annonin I ( 1) and anonin VI ( 9) were isolated from the seeds of ANNONA SQUAMOSA
      L. (Annonaceae). The constitution of 1 is identical with that of squamocin,
      isolated by Fujimoto et al. (8). The relative configuration of 1 was elucidated
      by X-ray diffraction analysis of a derivative. The constitution and relative
      configuration of 9 was established by (13)C- and (1)H-NMR spectroscopy using data
      of derivatives.

PMID- 17221428
TI  - [Annonacins and Annonastatin from Annona squamosa].
AB  - Annonacin ( 1), annonacin A ( 6), and annonastatin ( 7) were isolated from the
      seeds of ANNONA SQUAMOSA L. (Annonaceae). Compounds 6 and 7 are described for the
      first time. The relative configuration of the tetrahydrofuran core of 1 (with
      hitherto unknown configuration), as well as those of compounds 6, and 7 were
      established by (13)C- and (1)H-NMR spectroscopy using data of the derivatives 8-
      11.

PMID- 17221429
TI  - Quantitative Determination of Allicin and Alliin from Garlic by HPLC*.
AB  - The procedure for allicin synthesis could be improved. The time for HPLC analysis
      of allicin was shortened by the application of different isocratic elution
      systems. Calibration was performed by use of an allicin/silica gel adsorbate as
      external standard and its allicin content could be confirmed by different
      methods. L-(+)-Alliin was synthesized and applied as external standard for the
      quantitative determination of alliin by HPLC. Diastereoisomers had been separated
      by repeated recrystallization. Fresh ALLIUM SATIVUM bulbs from different origins
      were analyzed with respect to allicin content after complete enzymatic conversion
      of alliin; allicin contents found were in the range of 0.4%. The corresponding
      alliin contents were in the range of 0.9%. For a comparative evaluation of the
      alliin- and the allicin-HPLC determination methods, commercially available garlic
      preparations were analyzed, demonstrating that both methods are appropriate.
      However, the application of the HPLC system for allicin determination, in
      addition to providing information on the alliin-dependent allicin-generating
      capacity, enables the simultaneous quantification of allicin transformation
      products, such as ajoenes, dithiins, and alkyl sulfides. It was found that, for
      quantitative GLC analysis of allicin, allicin has to be used as an external
      standard.

PMID- 17221430
TI  - A novel extraction procedure for psilocybin and psilocin determination in
      mushroom samples.

PMID- 17221431
TI  - Two New Diterpenoids from Salvia longipedicellata.

PMID- 17221432
TI  - Polyhydroxylated Triterpenes from Eriobotrya japonica.

PMID- 17221433
TI  - Sweet-Tasting Triterpene Glycoside Constituents of Abrus fruticulosus1.

PMID- 17221434
TI  - 6'-O-beta-D-Glucosylswertiamarine: A New Secoiridoid from Gentiana alpina.

PMID- 17221435
TI  - Isoflavones of Belamcanda chinensis.

PMID- 17221436
TI  - Structures of three new isoprenylated xanthones, cudraxanthones e, f, and g 1,2.
AB  - Three new isoprenylated xanthones, cudraxanthones E, F, and G along with a known
      xanthone, 6-deoxyisojacareubin, were isolated from the ethanol extract of the
      root bark of CUDRANIA TRICUSPIDATA (Moraceae), collected in China. The structures
      of cudraxanthones E, F, and G were shown to be 1-3, respectively, on the basis of
      spectral evidence.

PMID- 17221437
TI  - Lignans and Other Constituents of Centaurea sphaerocephala ssp. polyacantha.
AB  - Extraction of the aerial parts of CENTAUREA SPHAEROCEPHALA L. ssp. POLYACANTHA
      (Willd.) Dostal furnished the lignans (-)-matairesinol, (-)-arctigenin, and (-)
      arctiin, two sesquilignans lappaol A and a stereo- or structural isomer of
      lappaol A, and a new dithienylacetylene.

PMID- 17221438
TI  - Secoiridoid Glucosides Isolated from Gentiana gelida.
AB  - From the aerial parts of GENTIANA GELIDA two new strongly bitter acylsecoiridoid
      glucosides, gelidoside ( 1) and gentomoside ( 2), have been isolated along with
      five known secoiridoid glucosides, trifloroside ( 3), gentiopicroside ( 4),
      swertiamarin ( 5), eustomoside ( 6), and eustomorusside ( 7). The structures of
      the compounds were elucidated by a combination of spectroscopic methods (UV, IR,
      (1)H-NMR, 2D-NMR, EI- and FAB-MS).

PMID- 17221439
TI  - Flavonol Glycosides from Moghania faginea.
AB  - Five flavonol 3- O-glycosides were isolated from the leaves of MOGHANIA FAGINEA
      O. Ktze. Their structures were elucidated as quercetin-3-O-rhamnoside
      (quercitrin), myricetin-3-O-rhamnoside (myricitrin), quercetin-3-O-xyloxyl(1-
      >2)rhamnoside, myricetin-3-O-xylosyl(1-->2)rhamnoside and kaempferol-3-O-xylosyl
      (1-->2)rhamnoside by chromatographic methods (TLC, HPLC) and UV, IR, (1)H-NMR,
      (13)C-NMR and FAB-mass spectroscopy. These substances are described for the first
      time in MOGHANIA FAGINEA and some of them are new.

PMID- 17221440
TI  - Flavonoid Glycosides and Other Hydrophilic Compounds from Flowers of Heterotheca
      inuloides.
AB  - Ten flavonoid glycosides were identified in flowers of HETEROTHECA INULOIDES
      ("Mexican Arnica"). Their structures were established by spectral data (UV, (1)H
      NMR, (13)C-NMR, mass) and total acid hydrolysis as kaempferol 3-beta-glucoside, 3
      beta-galactoside, 3-beta-rutinoside, 3-beta-robinobioside, quercetin 3-beta
      glucoside, 3-beta-galactoside, 3-beta-glucuronide, 3-beta-glucuronide-6''
      methylester, 3-alpha- L-arabinoside, and 3-beta-rutinoside. Additionally,
      caffeic, protocatechuic, and chlorogenic acid as well as umbelliferone were
      found.

PMID- 17221441
TI  - 1H-NMR and 13C-NMR Assignments of Cryptolepine, A 3:4-Benz-delta-carboline
      Derivative Isolated from Cryptolepis sanguinolenta.

PMID- 17221442
TI  - Biphenyl Type Lignans and Costunolide from Manglietia garrettii.

PMID- 17221444
TI  - Errata.

PMID- 17221443
TI  - Alkaloids of Corydalis ramosa.

PMID- 17221445
TI  - [From the Gestaltkreis to synergetics: irreversible structural and dynamic
      functional couplings].
AB  - With the present contribution, we attempt to merge the work of several
      generations of physiology and psychosomatics. The common denominator in an array
      of observation levels appear in these works as the relationship between
      irreversible-structural and dynamic-functional couplings and synchronisations. In
      this context, studies on the level of the common brainstem system appear to be
      the base for a neuro-bio-psychic self-organisation. Studies culled from
      psychosomatics of Heidelberg, notably the Gestaltkreis theory, the Methodenkreis
      (methodological loop), the Bipersonalitat (bipersonality), and the
      Simultandiagnostik (simultaneous diagnostics) exhibit the origin of complex
      functions which have been analyzed and quantified employing nonlinear methods
      developed in synergetics. Relevance of coupling and synchronisation,
      desynchronisation, resp., is, however, not limited to the scope of psychosomatic
      medicine. Fixed or functional, they are essential constituents to
      neurophysiological processes, such as association, dissociation, resp. This
      equally holds for evidence based medicine which is to benefit from any dynamic
      process analysis.

PMID- 17221446
TI  - Cardenolides in Digitalis lanata Cells Transformed with Ti-Plasmids.
AB  - Crown galls were induced by transformation of leaves, leaf discs, and shoots of
      the plant DIGITALIS LANATA with the AGROBACTERIUM TUMEFACIENS strains C58 pTi
      C58, B6S3 pTi B6S3, and A136 pTi A6NCtmr-338::Tn5. Integration of plasmid DNA in
      the genome of D. LANATA was demonstrated by hybridization experiments. The
      transformed cells synthesized opines and showed hormone-autotrophic growth. The
      crown galls formed on leaves of D. LANATA plants contained digitoxigenin
      derivatives (up to 0.8 muimol digitoxin equivalents g (-1) dry weight).
      Transformed cell lines derived from the crown galls built cardenolides IN VITRO
      (ca. 0.03 mumol digitoxin equivalents g (-1) dry weight). The rate of cardenolide
      biosynthesis IN VITRO did not decrease during a cultivation period of 12 months.

PMID- 17221447
TI  - Studies on the Origin of (-)-alpha-Bisabolol and Chamazulene in Chamomile
      Preparations; Part I. Investigations by Isotope Ratio Mass Spectrometry (IRMS).
AB  - IRMS was used to determine the delta (13)C-and deltaD-values of dried plant
      material and essential oil fractions of CHAMOMILLA RECUTITA and VANILLOSMOPSIS
      ERYTHROPAPPA and of isolated components thereof. Both plants turned out to follow
      the same C (3) photosynthetic pathway. The carbon isotope ratios ( delta (13)C
      values) of chamomile-derived bisabolol ranged from -32 per thousando to -30 per
      thousand; the corresponding deltaD-values varied between -240 per thousand and 
      205 per thousand. VANILLOSMOPSIS bisabolol differed significantly, with delta
      (13)C-values of approximately -27 per thousand, and a deltaD-value of about -175
      per thousand. In addition, chamazulene of chamomiie was characterized by a delta
      (13)C-value of -31 per thousand, whereas in chamazulene from ACHILLEA MILLEFOLIUM
      lower carbon discrimination was found (delta (13)C = -30 per thousand). The delta
      (13)C-values allowed us to detect adulterations of chamomiie preparations. The
      isolation of bisabolol, a main ingredient of these preparations, and subsequent
      IRMS analysis is much more tedious than GC/IRMS, which makes it possible to
      determine the carbon isotope ratio of bisabolol without prior isolation. Only one
      commercial chamomiie preparation was completely free of non-chamomile admixtures.
      Our investigations clearly demonstrate that admixtures of natural compounds can
      be detected in chamomile oil and chamomile preparations even if there is no
      difference in the photosynthetic mechanism of the corresponding plants.

PMID- 17221448
TI  - 11-Acetyl-1,19-epoxydenudatine: A New Alkaloid from Aconitum barbatum.
AB  - A new diterpenoid alkaloid was isolated from the overground parts of ACONITUM
      BARBATUM Pers. (Ranuncluaceae). Its structure was elucidated by spectroscopic
      methods as 11-acetyl-1,19-epoxydenudatine.

PMID- 17221449
TI  - Essential oil polymorphism in finnish thymus species.
AB  - Chemical polymorphism concerning the essential oils of the genus THYMUS is a
      widespread phenomenon, especially in the northern species. The two Finnish
      species, T. SERPYLLUM ssp. SERPYLLUM and T. SERPYLLUM ssp. TANAENIS, turned out
      to form four different chemotypes each, with hedycaryol, germacra-1(10),5-dien-4
      ol, germacra-1(10),4-dien-6-ol, linalool, and linalyl acetate as type
      characterizing compounds. Otherwise the oils of the two subspecies were similar
      containing myrcene, TRANS-beta-ocimene, beta-caryophyllene, and germacrene D as
      the main terpene hydrocarbons. 1,8-Cineol and camphor represented another great
      portion in both oils. If Finland is regarded as an area of T. SERPYLLUM (s.l.), a
      total of six types of plants can be defined with regard to the essential oil
      chemistry only. Including the frequency of these six types at the four areas
      investigated, a certain gradient from the south to the north can be seen. A most
      interesting aspect is the fact that the most frequent, linalyl acetate containing
      chemotype of the northern Lapland has nearly the same oil composition as T.
      PRAECOX ssp. ARCTICUS in Island, Norway, and Greenland.

PMID- 17221450
TI  - Acetylenes from Atractylis koreana.
AB  - A reinvestigation of the rhizomes of ATRACTYLIS KOREANA afforded in addition to
      1,3-diacetoxytetradeca-6,12-diene-8,10-diyne reported previously (1) two new C
      (14)-polyacetylenes with an ene-diyn-ene-chromophor and one new C (14)
      polyacetylene beside two known compounds with an ene-diyne-diene-chromophor.
      Their structures were established by spectroscopic and chemical methods.

PMID- 17221451
TI  - New Furans from Cirsium chlorolepis.
AB  - From the roots of CIRSIUM CHLOROLEPIS (Compositae) two known compounds, 5
      hydroxymethyl-2-furancarboxaldehyde, and 5-methoxymethyl-2-furan-carboxaldehyde,
      and two new compounds, cirsiumal-dehyde ( 2), and cirsiumoside ( 3), were
      isolated. Their structures have been elucidated by means of UV, IR, (1)H-NMR,
      (13)C-NMR spectroscopy, and chemical reactions.

PMID- 17221452
TI  - Aromatic Constituents from Vladimiria souliei.
AB  - The polar parts of the title plant gave several lignans including six new ones
      named vladinol A-F. The structures were elucidated by high field (1)H-NMR
      spectroscopy and a few chemical reactions. The stereochemistry was determined by
      the observed NOE's and by comparison of the (1)H-NMR data with those of related
      lignans.

PMID- 17221453
TI  - Structures of four new isoprenylated xanthones, cudraxanthones h,i,j, and k1,2.
AB  - Four new isoprenylated xanthones, cudraxanthone H,I,J, and K were isolated from
      the ethanol extract of the root bark of CUDRANIA TRICUSPIDATA (Carr.) Bur.
      (Moraceae), collected in China. The structures of cudraxanthones H,I,J, and K
      were shown to be 1- 4, respectively, on the basis of chemical and spectral
      evidence.

PMID- 17221454
TI  - Comparative HPLC Analyses of Alkamides within the Achillea millefolium Group.
AB  - Petrol/Et (2)O extractable alkamides from the subterranean parts of different
      members of the ACHILLEA MILLEFOLIUM group were separated and compared by reversed
      phase HPLC. Apart from different retention times, each peak could be
      characterized by its typical UV spectrum obtained by on-line photodiode array
      detection. Based on previously isolated and identified alkamides, a library
      search program of UV spectra and corresponding retention times was prepared which
      greatly facilitated a general comparison of the different HPLC profiles. Apart
      from the dominating deca-2 E,4 E,6Z-trienoic piperideide in the European
      representatives ( A. MILLEFOLIUM, A. PANNONICA, A. COLLINA, A. ASPLENIIFOLIA, A.
      SETACEA), the different cytotypes may be characterized by various accumulation
      tendencies, mainly towards two isomeric decatetraenoic piperideides and (+)
      sesamin. The amide patterns of the Asian and North American members ( A.
      ASIATICA, A. LANULOSA) clearly deviate; the characteristic decatrienoic and
      decatetraenoic piperideides are replaced here by a preponderance of decadienoic
      acid-derived isobutylamide and piperideide. Since there are no diploid members
      known from North America, the striking chemical similarities with the diploid
      Asian members strongly suggest an Asian origin.

PMID- 17221455
TI  - (-)-5alpha-Hydroxysophocarpine, a New Lupin Alkaloid from the Seeds of Sophora
      flavescens var. angustifolia1.

PMID- 17221456
TI  - Accumulation of Rare Phenylpropanoids in Agrobacterium rhizogenes Transformed
      Root Cultures of Coreopsis tinctoria.

PMID- 17221457
TI  - Procyanidins in Callus and Multiple Shoot Cultures of Hypericum erectum1.

PMID- 17221458
TI  - Alkaloids of Siparuna tonduziana.

PMID- 17221818
TI  - [Clinical criteria of Parkinson's disease].
AB  - The clinical criteria of Parkinson's disease are akinesia in combination with at
      least one of the following three symptoms: tremor (asymmetrical resting tremor),
      rigidity, impairment of posture, gait and balance. Symptomatic and atypical
      parkinsonian syndromes are ruled out by history, clinical examination, cranial
      CT, MRI, SPECT or PET. Patients with Parkinson's disease respond to levodopa or
      dopaminagonists throughout the course of the disease. Parkinson's disease is also
      characterised by various vegetative symptoms, impairment of olfaction, anxiety,
      depression, and with increasing age also by cognitive deficits and dementia.

PMID- 17221819
TI  - [Differential diagnosis of Parkinson's disease].
AB  - For a long time the diagnosis of Parkinson's disease has been considered to be
      easy. The advantages in treatment in the last decennia have shown that a more
      sophisticated differentiation from certain syndromes, which will be shortly
      described, is mandatory in order to achieve optimal therapeutic responses and for
      giving a prognosis.

PMID- 17221820
TI  - [Medical treatment of Parkinson's disease].
AB  - Our understanding of Parkinson's disease (PD) has evolved. Parkinson's disease is
      no longer regarded a pure motor disorder, but a complex disease with motor as
      well as non-motor symptoms, the latter having a major impact on the quality of
      life of the patient as well as the caregiver. After a few years of suffering from
      PD, complications of therapy add invariably to the burden of the disease. Many of
      these complications are not volunteered by the patient or the caregiver, either
      due to their embarrassing nature or due to lack of insight of their causal
      relationship with PD or the treatment of PD. However, proper treatment of PD has
      to address the non-motor symptoms and the complications of therapy as well.

PMID- 17221821
TI  - [Surgery for Parkinson's disease].
AB  - Surgery for Parkinson's Disease (PD) is being increasingly used. The main reason
      for this renewal in surgical treatment for PD is the "deep brain stimulation"
      (DBS) that replaced the previously used stereotactic lesions in most centers. DBS
      allows a focal specific electrical stimulation of basal ganglia target instead of
      an irreversible lesion. Mainly bilateral DBS of the nucleus subthalamicus is now
      an established surgical treatment for PD. But DBS of the Globus pallidus internus
      and of the thalamus should still be considered in selected patients. DBS is an
      efficient treatment for motor complication of PD that can no longer be controlled
      by drug treatment. Dyskinesia, bradykinesia, tremor and rigor can be improved by
      DBS and the medication can be reduced. It is still unclear, however, how the
      improvement in motor symptoms affects quality of life in the long term.
      Furthermore, patients with severe cognitive and psychiatric symptoms as well as
      patients with severe axial symptoms should not be operated since these symptoms
      may worsen after surgery.

PMID- 17221822
TI  - [Rehabilitation of parkinsonian patients].
AB  - Although most parkinsonian patients greatly benefit from medical and/or surgical
      treatment, their clinical management should not be limited to these two
      interventions. Axial symptoms, freezing, postural instability, speech and
      swallowing problems may be drug-resistant, and disability may persist in spite of
      improvement of motor symptoms. A coordinate interdisciplinary approach
      facilitates the clinical management of the disease. Physiotherapy, occupational
      therapy and speech therapy may contribute to reduce impairment and improve
      quality of life; a psychological and social support of patients and caregivers
      helps them carrying the burden of the disease; counseling through a specialized
      nurse may give practical solutions to problems like bladder incontinence,
      symptomatic hypotension or hypersalivation. As sensory cueing may help patients
      bypassing the disease-specific motor control deficits, it should be included in
      training programs. Rehabilitatory interventions are part of the standards of care
      of Parkinson's disease and their efficacy is supported by several
      neurophysiological and clinical investigations. However, the poor methodological
      quality of most clinical studies as compared with the standard of pharmacological
      investigations fails to provide clear-cut evidence in favour of rehabilitation.

PMID- 17221823
TI  - [Tremor].
AB  - Tremor is one of the most frequent neurological signs. The correct clinical
      classification is mainly clinical. The most frequent primarily neurological
      tremor is essential tremor (prevalence 2 to 5%). It presents in most cases as a
      more or less symmetrical postural and kinetic tremor. In about 60% of cases an
      autosomal-dominant inheritance is found. Tremor may manifest not only in the
      hands but also in the head and voice. In about 60 to 70% of the patients alcohol
      may improve the tremor. Parkinsonian tremor is normally a tremor at rest and it
      starts asymmetrically. The legs and the face are frequently involved. Cerebellar
      tremor is intentional. Orthostatic tremor, which has a high frequency, mainly
      manifests in the legs and gives rise to postural instability. Dystonic tremor is
      an action tremor of the affected region of the body. Drug therapy, which is
      purely symptomatic, mostly depends on clinical manifestation. Postural and action
      tremors respond to non selective betablockers (propranolol), primidone, some
      antiepileptics (gabapentin, toparimate) and benzodiazepines. Classical rest
      tremors are improved by dopaminergic substances (levodopa, dopamine agonists) or
      anticholinergics. Dystonic tremor may successfully be treated by injections of
      botulinum toxin. Orthostatic tremor responds to gabapentin or benzodiazepines in
      some of the patients. In severely handicapped patients with refractory tremors
      the implantation of thalamic stimulation electrodes may be considered. This
      treatment may be very successful, however, its inherent risks have to be taken
      into account.

PMID- 17221824
TI  - [The dystonias--botulinum toxin, deep brain stimulation, pharmacotherapy, motor
      training].
AB  - Despite great advances in the understanding of the dystonias, treatment for most
      patients remains symptomatic. Botulinum neurotoxin (BoNT) is the treatment of
      choice for focal dystonias. Selected issues related to the use of BoNT are
      highlighted with pertinent illustrations. In certain focal, mainly in generalised
      dystonias BoNT may not be sufficient or appropriate. Besides BoNT
      pharmacotherapy, nowadays increasingly deep brain stimulation, psychotherapy,
      physio- and occupational therapy approaches can be included in the management of
      dystonic patients. The review focuses on experiences with established management
      guidelines and new developments in the treatment of dystonias.

PMID- 17221825
TI  - [Chorea].
AB  - Chorea (from the greek word "dance") is characterized by short, involuntary,
      irregular, nonrepetitive, adventitious muscular contractions. The resulting
      movements may occur abruptly at any part of the body, but may also spread from
      one body part to another. The most important condition showing chorea as its core
      symptom is Huntington's disease. It is inherited as an autosomal dominant trait.
      During its course it presents as an admixture of neurological and psychiatric
      features. Several rare neurodegenerative diseases and conditions of inborn errors
      of metabolism present with chorea mostly between childhood and adolescence. Among
      these, the paroxysmal choreoathetoses are important for the differential
      diagnosis of seizures and transitory ischaemic attacks later in life. In adults,
      symptomatic chorea may occur in many drug-induced, metabolic, infectious,
      immunological, toxic, and vascular conditions. In addition to the basic
      treatments of these illnesses there are selected drugs to provide satisfactory
      symptomatic relief from the abnormal movement.

PMID- 17221826
TI  - [Wilson's disease].
AB  - Wilson's disease is a rare autosomal recessive disorder of hepatic copper
      transport leading to a biliary excretion inhibition of copper. Overload of the
      metal mainly in liver and basal ganglia leads to hepatic but also to
      extrapyramidal motor as well as psychiatric clinical symptoms. Diagnosis is based
      on clinical suspicion, parameters of copper metabolism, ophthalmic examination
      and a liver biopsy. A radiocopper test is able to identify patients even with
      inconsistent laboratory results. For initial assessment and follow-up
      neurophysiological investigation and MRI are recommended additionally. Genetic
      analysis can be helpful to detect asymptomatic relatives of the index patient.
      Dependent on the stage of the disease for therapy chelating drugs and zinc are
      possible but must be given lifelong without longer interruptions. With early
      diagnosis and consequent treatment the prognosis of Wilson's disease is excellent
      and usually the need for liver transplantation can be prevented.

PMID- 17221827
TI  - [Sleep and movement disorders].
AB  - The three different states of being (wakefulness, NREM and REM sleep) are
      associated with profound neurophysiological and neurochemical changes in the
      brain. These changes explain the existence of movement disorders appearing only
      or preferentially during sleep, and the effects of sleep on movement disorders.
      Sleep-related movement disorders are of clinical relevance for multiple reasons:
      1) high frequency (e.g. restless legs syndrome (RLS)); 2) diagnostic relevance
      (e.g. REM sleep behavior disorder (RBD) as first manifestation of Parkinson
      disorder); 3) diagnostic uncertainty (e.g. parasomnias vs nocturnal epilepsy); 4)
      association with injuries (e.g. RBD, sleepwalking), sleep disruption/daytime
      sleepiness (e.g. RLS), and psycho-social burden (e.g. enuresis); 5) requirement
      of specific treatments (e.g. nocturnal epilepsy, stridor, RBD). This article
      gives an overview on clinical manifestations, pathophysiology, work-up and
      treatment of sleep-related movement disorders (e.g. RLS, bruxism), parasomnias
      (e.g. sleepwalking, RBD), sleep-related epilepsies, and on sleep-associated
      manifestations of movement disorders (e.g. Parkinson disease, multiple system
      atrophy).

PMID- 17221828
TI  - Opuntia ficus indica (L.) Mill. mucilages show cytoprotective effect on gastric
      mucosa in rat.
AB  - Opuntia ficus indica cladodes possess a protective action against ethanol-induced
      ulcer in the rat. The major components of cladodes are carbohydrate polymers,
      mainly mucilages and pectin. To clarify the cytoprotective effects of cladodes on
      experimental ethanol-induced ulcer in rat, mucilages and pectin were extracted
      and were administered instead of cladodes. The above mentioned effects induced by
      cladodes may be attributed to mucilages, and not significantly to pectin.

PMID- 17221829
TI  - In Vivo antimalarial activity of aqueous extracts from Kenyan medicinal plants
      and their chloroquine (CQ) potentiation effects against a blood-induced CQ
      resistant rodent parasite in mice.
AB  - Hot water extracts from eight medicinal plants representing five families, used
      for malaria treatment in Kenya were screened for their in vivo antimalarial
      activity in mice against a chloroquine (CQ) resistant Plasmodium berghei NK65,
      either alone or in combination with CQ. Extracts of three plants, Toddalia
      asiatica (root bark), Rhamnus prinoides (leaves and root bark) and Vernonia
      lasiopus (root bark) showed high chemosuppression in the range 51%-75%. Maytenus
      acuminata, M. heterophylla, M. senegalensis and Rhamnus staddo had moderate
      activities of 33%-49% parasitaemia suppression in the root bark and/or leaf
      extracts, while Withania somnifera (root bark) had a non-significant suppression
      (21%). In combination with CQ, extracts of V. lasiopus (all parts), leaf extracts
      of M. senegalensis, R. prinoides and T. asiatica as well as root barks of M.
      heterophylla, R. staddo and T. asiatica had improved parasitaemia suppression in
      the range 38%-66%, indicating synergistic interactions. Remarkable parasitaemia
      suppression by the extracts, either alone or in combination with CQ resulted into
      longer survival of mice relative to the controls, in some cases by more than 2
      weeks. Plants, which showed significant antimalarial activity including V.
      lasiopus, T. asiatica and R. prinoides, should further be evaluated in the search
      for novel agents against drug-resistant malaria.

PMID- 17221830
TI  - Toxicological studies on hydroalcohol extract of Calendula officinalis L.
AB  - The hydroalcohol extract (HAE) of Calendula officinalis L. was evaluated for its
      acute toxicity by the oral route in rats and mice and for the subacute effect on
      hematological, biochemical and morphologic parameters in rats. In the acute
      toxicity test, HAE failed to cause death in the animals after administration of
      oral doses up to 5.0 g/kg. Oral treatment with HAE at 0.025, 0.25, 0.5 and 1.0
      g/kg did not induce hematological alterations when compared with the control
      group. In the biochemical parameters, there was an increase in blood urea
      nitrogen (BUN) and in alanine transaminase (ALT) levels. Morphological
      examination of the brain, kidney and heart did not show any alteration. However,
      inflammatory sites were found in the lung and liver, which were associated,
      respectively, with oral gavage and a possible hepatotoxic effect. HAE was non
      toxic in rats, although there was evidence of renal and liver overload.

PMID- 17221831
TI  - The G51S purine nucleoside phosphorylase polymorphism is associated with
      cognitive decline in Alzheimer's disease patients.
AB  - Alzheimer's disease (AD) is a polygenic and multifactorial complex disease, whose
      etiopathology is still unclear, however several genetic factors have shown to
      increase the risk of developing the disease. Purine nucleotides and nucleosides
      play an important role in the brain. Besides their role in neurotransmission and
      neuromodulation, they are involved in trophic factor release, apoptosis, and
      inflammatory responses. These mediators may also have a pivotal role in the
      control of neurodegenerative processes associated with AD. In this report the
      distribution of the exonic G/A single nucleotide polymorphism (SNP) in purine
      nucleoside phosphorylase (PNP) gene, resulting in the amino acid substitution
      serine to glycine at position 51 (G51S), was investigated in a large population
      of AD patients (n=321) and non-demented control (n=208). The PNP polymorphism
      distribution was not different between patients and controls. The polymorphism
      distribution was also analyzed in AD patients stratified according to
      differential progressive rate of cognitive decline during a 2-year follow-up. An
      increased representation of the PNP AA genotype was observed in AD patients with
      fast cognitive deterioration in comparison with that from patients with slow
      deterioration rate. Our findings suggest that the G51S PNP polymorphism is
      associated with a faster rate of cognitive decline in AD patients, highlighting
      the important role of purine metabolism in the progression of this
      neurodegenerative disorder.

PMID- 17221832
TI  - Linked surveys of health services utilization.
AB  - The linked population/establishment survey (LS) of health services utilization is
      a two-phase sample survey that links the sample designs of the population sample
      survey (PS) and the health-care provider establishment sample survey (ES) of
      health services utilization. In Phase I, household respondents in the PS identify
      their health-care providers during a specified calendar period. In Phase II,
      health-care providers identified in Phase I report the variables of interest for
      all or a sample of their transactions with all households during the same
      calendar period. The LS has been proposed as a potential design alternative to
      the PS whenever the health-care transactions of interest are hard to find or
      enumerate in household surveys and as a potential design alternative to the ES
      whenever it is infeasible or expensive to construct or maintain complete sampling
      provider frames that list all health-care providers with good measures of
      provider size. Suppose that the non-sampling errors are ignorable, how do the LS,
      PS and ES sampling errors compare? This paper addresses that question by
      summarizing and extending recent research findings that compare expressions of
      the sampling variance of (1) the LS and PS of equivalent household sample size
      and (2) the LS and the ES of equivalent expected health-care provider and
      transaction sample sizes. The paper identifies the parameters contributing to the
      precision differences and assesses the conditions that favour the LS or one or
      the other surveys. Published in 2007 by John Wiley & Sons, Ltd.

PMID- 17221833
TI  - Using hierarchical models to attribute sources of variation in consumer
      assessments of health care.
AB  - The Consumer Assessments of Healthcare Providers and Systems (CAHPS) Medicare
      Advantage (MA-CAHPS) survey has provided extensive and uniform data for 8 years
      on the quality of Medicare health plans in the United States. The complex
      structure of the data makes hierarchical modelling an appropriate analytic tool.
      After describing the CAHPS survey and the analytic methods used in standard
      reports, we review research using two multilevel modelling strategies, each
      addressing a different aspect of the structure of the CAHPS data. The first fits
      a 2-level Fay-Herriott-type model to data aggregated by plan to estimate plan
      level correlations among summary scores on different items. By forming separate
      measures for healthier and sicker members of each plan, we were able to determine
      which items measured distinct dimensions of quality depending on health status.
      The second analysis evaluated the relative contributions of geography and
      organizational units to the various quality measures, and the amount of variation
      over time in each. Geographical variation predominated for aspects of member
      experiences that are not typically under the direct control of plans, and the
      geographical effects were very stable over time. Each of the two analyses can be
      regarded as a simplification for particular objectives of a larger underlying
      model. Further methodological development is needed to better characterize
      variation in quality.

PMID- 17221834
TI  - Renal protection by delayed ischaemic preconditioning is associated with
      inhibition of the inflammatory response and NF-kappaB activation.
AB  - Brief and sublethal ischaemia renders an organ tolerant to subsequent prolonged
      ischaemia, which is called ischaemic preconditioning (IPC). In regard to the
      beneficial effects and endogenous mechanisms of renal delayed IPC, few data are
      available. In this study, we aim at determining reno-protective effects of
      delayed IPC against ischaemia-reperfusion (I/R) injury, and illustrating whether
      these effects are associated with suppressing inflammation and nuclear factor
      kappaB (NF-kappaB) activation. I/R injury was induced by clamping both renal
      pedicles for 40 min, followed by 24 h of reperfusion. The rats were subjected to
      ischaemia for 20 min (preconditioning) or sham surgery (non- preconditioning) at
      day 4 before I/R. Functional and morphological parameters were evaluated at 24 h
      after reperfusion. At the same time, macrophage (ED-1(+)) infiltration, and the
      expression of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis
      factor-alpha (TNF-alpha) were assessed by immunohistochemistry. Moreover, I kappa
      B-alpha degradation and NF-kappaB/DNA binding activity were analyzed. Compared
      with rats exposed to I/R injury, preconditioned rats had a significant decrease
      in levels of serum creatinine (Scr, 384.3 +/- 21.8 micromol/L vs. 52.5 +/- 21.7
      micromol/L; p<0.001), blood urea nitrogen (BUN, 40.4 +/- 2.7 mmol/L vs. 15.9 +/-
      4.2 mmol/L; p<0.001) and serum aspartate aminotransferase (AST, 486.7 +/- 58.6
      IU/L vs. 267.3 +/- 43.9 IU/L; p<0.001). Parallel to the above changes,
      preconditioned rats preserved structural integrity and decreased
      tubulointerstitial damage scores (3.4 +/- 0.3 vs. 0.2 +/- 0.05; p<0.001) and ED
      1(+) cell infiltration (25.3 +/- 3.5 vs. 6.2 +/- 1.2 cells/HPF, p<0.01).
      Furthermore, our results showed that the expression of ICAM-1 and TNF-alpha, the
      degree of I kappa B-alpha degradation, and NF-kappaB/DNA binding activity were
      reduced by IPC. Taken together, our results demonstrated that delayed IPC offered
      both functional and histological protection, which may be related to suppression
      of inflammation in preconditioned kidneys.

PMID- 17221835
TI  - HIV viral dynamic models with dropouts and missing covariates.
AB  - In recent years HIV viral dynamic models have received great attention in AIDS
      studies. Often, subjects in these studies may drop out for various reasons such
      as drug intolerance or drug resistance, and covariates may also contain missing
      data. Statistical analyses ignoring informative dropouts and missing covariates
      may lead to misleading results. We consider appropriate methods for HIV viral
      dynamic models with informative dropouts and missing covariates and evaluate
      these methods via simulations. A real data set is analysed, and the results show
      that the initial viral decay rate, which may reflect the efficacy of the anti-HIV
      treatment, may be over-estimated if dropout patients are ignored. We also find
      that the current or immediate previous viral load values may be most predictive
      for patients' dropout. These results may be important for HIV/AIDS studies.

PMID- 17221836
TI  - When behavioral assessment detects frontotemporal dementia and cognitive testing
      does not: data from the Frontal Behavioral Inventory.

PMID- 17221837
TI  - Kallikrein 4 is a potential mediator of cellular interactions between cancer
      cells and osteoblasts in metastatic prostate cancer.
AB  - BACKGROUND: Prostate cancer (PCa) and bone cell interactions are critical in the
      metastatic phase. Kallikrein 4 (KLK4/hK4) is expressed in both PCa and
      mineralized tissues. We determined if KLK4/hK4 expression was associated with,
      and influenced by, the bone environment of metastatic PCa. METHODS:
      Immunohistochemistry, in vitro co-culture, cell migration, and attachment assays.
      RESULTS: hK4 was localized to tumor cells and osteoblasts in bone metastases.
      KLK4/hK4 increased in LNCaP and PC3 cells co-cultured with SaOs2 cells; SaOs2
      KLK4/hK4 was unchanged. Co-culture did not affect cell proliferation but altered
      alkaline phosphatase activity/mRNA levels in SaOs2 cells. KLK4-transfected PC3
      cells had increased migration towards SaOs2 conditioned medium and greater
      attachment to the bone-matrix proteins, collagens I and IV. CONCLUSIONS: hK4
      expression and interaction with both tumor cells and osteoblasts suggests a role
      for hK4 in PCa bone metastasis. Whether this observation is unique to bone
      metastasis or reflects a role for hK4 in PCa metastasis generally is yet to be
      established.

PMID- 17221838
TI  - Association of adenomatous polyposis coli (APC) gene polymorphisms with autism
      spectrum disorder (ASD).
AB  - We serendipitously identified a single nucleotide polymorphism (SNP), 8636C>A
      (rs1804197) in the 3'-untranslated region of the adenomatous polyposis coli (APC)
      gene to be associated with autism spectrum disorder (ASD). In order to gain
      further evidence for the association between the APC locus and ASD, we genotyped
      four additional adjacent common SNPs (rs2229992, rs42427, rs459552, and rs465899)
      in the coding regions within the APC gene in a set of Swedish ASDs and controls.
      One common haplotype TGAG was found to be associated with ASD after haplotype
      analysis using both Haploview v3.1.1 (P = 0.006) and COCAPHASE v2.403 (P =
      0.030). This result is the first to suggest that the genomic locus at APC is
      associated with ASD, and that the APC gene itself is a good predisposing
      candidate to be evaluated in future studies due to its important role in neuronal
      development and function.

PMID- 17221839
TI  - Association study of polymorphisms in the glutamate transporter genes SLC1A1,
      SLC1A3, and SLC1A6 with schizophrenia.
AB  - Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis,
      we have been performing systematic association studies of schizophrenia with the
      glutamate receptor and transporter genes. We report here association studies of
      schizophrenia with three glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6
      encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We
      initially performed the screening of the total 25 single nucleotide polymorphisms
      (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases
      and 100 out of 420 Japanese controls. After controlling the false discovery rate
      (FDR) at level 0.05, we observed significant associations of schizophrenia with a
      genotype of SNP4 (rs2097837, P = 0.007) and with haplotypes of SNP2-SNP5 (P = 7.5
      x 10(-5)) and SNP3-SNP5 (P = 9.0 x 10(-4)) in the SLC1A6 region. The haplotype of
      SNP2-SNP5 of SLC1A6 even showed marginally significant association with the
      disease in the full-size sample (400 cases and 420 controls, P = 0.031). We
      concluded that at least one susceptibility locus for schizophrenia may be located
      within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major
      susceptibility genes for schizophrenia in the Japanese population.

PMID- 17221840
TI  - Differential expression and parent-of-origin effect of the 5-HT2A receptor gene
      C102T polymorphism: analysis of suicidality in schizophrenia and bipolar
      disorder.
AB  - The serotonin 2A (5-HT2A) receptor gene has been implicated in the pathogenesis
      of suicidal behavior by a genetic association between the 5-HT2A C102T silent
      polymorphism and suicidality in patients with major depression. However, a recent
      meta-analysis failed to confirm this association. We developed an improved
      quantitative assay for the measurement of allele-specific expression of the 5
      HT2A gene, and find that the ratio of C/T allele expression in the pre-frontal
      cortex of heterozygous suicide victims (n = 10) was significantly decreased in
      comparison with the non-suicide group (n = 10) (P = 0.049). Because the 5-HT2A
      gene is subject to imprinting, the parent-of-origin may affect the inheritance of
      suicidal behavior. Thus we examined the parental origin of specific alleles for
      genetic association in a genetic family-based sample of major psychoses in which
      information on suicidal behavior was available. No association between the 5-HT2A
      C102T polymorphism and suicidal behavior in major psychoses was detected with the
      transmission/disequilibrium test (TDT).

PMID- 17221841
TI  - The Hsp90 inhibitor, 17-AAG, prevents the ligand-independent nuclear localization
      of androgen receptor in refractory prostate cancer cells.
AB  - BACKGROUND: Androgen receptor (AR) is the key molecule in androgen-refractory
      prostate cancer. Despite androgen ablative conditions, AR remains active and is
      necessary for the growth of androgen-refractory prostate cancer cells. Nuclear
      localization of AR is a prerequisite for its transcriptional activation. We
      examined AR localization in androgen-dependent and androgen-refractory prostate
      cancer cells. METHODS AND RESULTS: We demonstrate increased nuclear localization
      of a GFP-tagged AR in the absence of hormone in androgen-refractory C4-2 cells
      compared to parental androgen-sensitive human prostate cancer LNCaP cells.
      Analysis of AR mutants impaired in ligand-binding indicates that the nuclear
      localization of AR in C4-2 cells is truly androgen-independent. The hsp90
      inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), inhibits basal PSA
      expression and disrupts the ligand-independent nuclear localization of AR at
      doses much lower than required to inhibit androgen-induced nuclear import.
      CONCLUSIONS: Hsp90 is a key regulator of ligand-independent nuclear localization
      and activation of AR in androgen-refractory prostate cancer cells.

PMID- 17221842
TI  - Prostate-derived factor as a paracrine and autocrine factor for the proliferation
      of androgen receptor-positive human prostate cancer cells.
AB  - BACKGROUND: The expression of prostate-derived factor (PDF) is significantly
      elevated in human prostate tumors. We investigate the functional role and
      signaling of PDF in androgen receptor (AR)-positive human prostate cancer cells.
      METHODS: Transient or stable expression of PDF by cDNA transfection, antisense
      mediated gene silencing, media conditioned by PDF-elevated cells, and antibody
      (Ab) neutralization were employed. RESULTS: Elevated endogenous and exogenous
      expression of PDF and treatment of PDF-enriched media were associated with
      increased proliferation and clonogenic growth of the cells. On the contrary,
      knockdown of PDF or addition of PDF neutralizing Ab resulted in diminished
      proliferation and reduced anchorage-independent growth. Further, ERK1/2 and
      p90RSK, but not Smad2/3, were activated in PDF-elevated cells as well as in cells
      treated with PDF-enriched media, while inhibition of ERK1/2 decreased the growth
      of those cells. CONCLUSION: PDF promotes AR-positive prostate tumor progression
      through upregulating cell proliferation via ERK1/2 signal pathway.

PMID- 17221843
TI  - Vascular endothelial growth factor and angiopoietin are required for prostate
      regeneration.
AB  - BACKGROUND: The regulation of the prostate size by androgens may be partly the
      result of androgen effects on the prostatic vasculature. We examined the effect
      of changes in androgen levels on the expression of a variety of angiogenic
      factors in the mouse prostate and determined if vascular endothelial growth
      factor (VEGF)-A and the angiopoietins are involved in the vascular response to
      androgens. METHODS: Expression of angiogenic factors in prostate was quantitated
      using real-time PCR at different times after castration and after administration
      of testosterone to castrated mice. Angiopoietins were localized in prostate by
      immunohistochemistry and in situ hybridization. The roles of VEGF and the
      angiopoietins in regeneration of the prostate were examined in mice inoculated
      with cells expressing soluble VEGF receptor-2 or soluble Tie-2. RESULTS:
      Castration resulted in a decrease in VEGF-A, VEGF-B, VEGF-C, placenta growth
      factor, FGF-2, and FGF-8 expression after 1 day. In contrast, VEGF-D mRNA levels
      increased. No changes in angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2),
      hepatocyte growth factor, VEGF receptor-1, VEGF receptor-2, or tie-2 mRNA levels
      were observed. Administration of testosterone to castrated mice had the opposite
      effect on expression of these angiogenic factors. Ang-2 was expressed
      predominantly in prostate epithelial cells whereas Ang-1 was expressed in
      epithelium and smooth muscle. Inoculation of mice with cells expressing soluble
      VEGF receptor-2 or Tie-2 blocked the increase in vascular density normally
      observed after administration of testosterone to castrated mice. The soluble
      receptors also blocked the increase in prostate weight and proliferation of
      prostatic epithelial cells. CONCLUSION: VEGF-A and angiopoietins are required for
      the vascular response to androgens and for the ability of the prostate to
      regenerate in response to androgens.

PMID- 17221845
TI  - Genetic analysis of SCA 27 in ataxia and childhood onset postural tremor.

PMID- 17221846
TI  - Association of a serotonin receptor 2A gene polymorphism with cognitive functions
      in patients with schizophrenia.
AB  - The aim of this study was to investigate the association between the T102C
      polymorphism on the 5HT2A gene and cognitive function as well as clinical
      manifestations in patients with schizophrenia. Eighty-two outpatients with
      schizophrenia participated in this study. The Brief Psychiatric Rating Scale
      (BPRS) was used to assess the severity of each patient's symptoms. In order to
      evaluate their short-term attention capacity, a Digit Span Test was used. The
      Continuous Performance Test (CPT) was used to test the sustained attention span
      of each of the subjects. Cognitive flexibility was measured with the Wisconsin
      Card Sorting Test (WCST). The polymorphism of the 5-HT2A gene at codon 102 (T/C)
      was genotyped by sequence specific polymerase chain reaction. The T allele at
      codon 102 correlated with a lower hit rate and more commission errors in the CPT
      and patients with the heterogeneous genotype (TC) had more commission errors than
      those who were of homogeneous type (CC or TT). Patients with the TC genotype also
      had significantly fewer correct responses in the WCST compared to those who were
      type CC or TT. No relationship was found to exist between the C allele and
      cognitive variables. There was also no relationship established between the codon
      102 polymorphism and clinical parameters. These findings suggest that the TC
      genotype might be related to certain cognitive impairments in patients with
      schizophrenia.

PMID- 17221844
TI  - Dendritic cells program non-immunogenic prostate-specific T cell responses
      beginning at early stages of prostate tumorigenesis.
AB  - BACKGROUND: Prostate cancer promotes the development of T cell tolerance towards
      prostatic antigens, potentially limiting the efficacy of prostate cancer vaccines
      targeting these antigens. Here, we sought to determine the stage of disease
      progression when T cell tolerance develops, as well as the role of steady state
      dendritic cells (DC) and CD4(+)CD25(+) T regulatory cells (Tregs) in programming
      tolerance. METHODS: The response of naive HA-specific CD4(+) T cells were
      analyzed following adoptive transfer into Pro-HA x TRAMP transgenic mice
      harboring variably-staged HA-expressing prostate tumors on two genetic
      backgrounds that display different patterns and kinetics of tumorigenesis. The
      role of DC and Tregs in programming HA-specific CD4 cell responses were assessed
      via depletion. RESULTS: HA-specific CD4 cells underwent non-immunogenic responses
      at all stages of tumorigenesis in both genetic backgrounds. These responses were
      completely dependent on DC, but not appreciably influenced by Tregs. CONCLUSIONS:
      These results suggest that tolerogenicity is an early and general property of
      prostate tumors.

PMID- 17221847
TI  - The influence of four serotonin-related genes on decision-making in suicide
      attempters.
AB  - Genetic factors have been associated with the vulnerability to suicidal behavior.
      We previously reported decision-making impairment in suicide attempters and
      hypothesized that these cognitive alterations may represent an endophenotype of
      suicidal behavior. In this study, we aimed to investigate the influence of four
      serotonin-related genes relevant to suicidal behavior on decision-making, in a
      large population of suicide attempters. The Iowa Gambling Task was used to assess
      decision-making in 168 patients with a personal history of attempted suicide.
      Patients were genotyped for four serotonergic polymorphisms: 5HTTLPR, TPH1 A218C,
      MAOA u-VNTR, and TPH2 rs1118997. Patients carrying the 5HTTLPR-ll and -sl, TPH1
      CC and -AC, MAOA-HH (in women) and TPH2-AA genotypes significantly improved their
      performance during the task, suggesting a genetic modulation of the learning
      process required for advantageous decision-making. In contrast, genotypes
      previously associated with a higher risk of suicidal behavior, a greater
      sensitivity to the environment and a higher propensity to negative feelings are
      those conferring poorer learning abilities. We hypothesize that the influence of
      genetic factors on the vulnerability to suicidal behavior may partly be achieved
      through their modulation of decision-making and particularly its learning
      component.

PMID- 17221848
TI  - Actimetric evidence that CLOCK 3111 T/C SNP influences sleep and activity
      patterns in patients affected by bipolar depression.
AB  - Depressive insomnia and diurnal fluctuations of mood and activity are core
      clinical features of mood disorders. Here we studied the effect of CLOCK 3111 T/C
      SNP (rs1801260) on the actimetric recorded diurnal activity and nocturnal sleep
      of 39 bipolar depressed inpatients. Compared to T/T homozygotes, carriers of the
      C allele had a similar degree of severity of depression, but showed higher
      activity levels in the evening, a delayed sleep onset (mean 79 min later), and a
      reduced amount of sleep during the night (mean 75 min less). Ongoing lithium
      treatment significantly interacted with rs1801260 by enhancing activity levels in
      the evening and reducing the differences among genotype groups. Individual
      characteristics of the molecular clock can influence sleep symptoms in mood
      disorders.

PMID- 17221849
TI  - Investigation of drug-porous adsorbent interactions in drug mixtures with
      selected porous adsorbents.
AB  - The adsorption of drugs onto porous substrates may prove to be a convenient
      method by which to enhance the dissolution rate of certain poorly water-soluble
      drugs in body fluids. The purpose of this research is to provide a better
      understanding of the type of interactions occurring between drugs and certain
      pharmaceutically acceptable porous adsorbents that leads to enhanced drug
      dissolution rates. The interactions between ibuprofen (acidic drug),
      acetaminophen (acidic drug), dipyridamole (basic drug), and the porous adsorbents
      used (calcium silicate and silica gel) were investigated using differential
      scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier
      Transform infrared spectroscopy (FTIR). DSC and PXRD results indicated a
      significant loss of crystallinity of both ibuprofen and acetaminophen but not
      dipyridamole. In the case of ibuprofen, FTIR results indicated the ionization of
      the carboxylic group based on the shift in the FTIR carboxylic band. Dissolution
      of ibuprofen from its mixtures with porous adsorbents was found to be
      significantly higher compared to the neat drug, whereas dipyridamole dissolution
      from its mixtures with porous adsorbents was not significantly different from
      that of the neat drug.

PMID- 17221850
TI  - Faecal incontinence.
AB  - BACKGROUND: Faecal incontinence is a life style-limiting condition with multiple
      aetiologies. Surgical cure is not often possible. METHODS AND RESULTS: A review
      of the literature was undertaken using Medline, Cochrane database and standard
      textbooks. Advanced imaging techniques now inform the treatment algorithm and
      objectively assess success. The long-term outcome of anal surgery is uncertain.
      Modern approaches favour conservative measures, such as biofeedback, and less
      invasive surgical procedures. Stoma formation is a definitive option for some
      patients. CONCLUSION: Current treatment of faecal incontinence is evolving from a
      sphincter-focused view to a more holistic one, recognizing the influence of the
      pelvic floor and psyche in maintaining continence. Modern imaging modalities
      direct treatment strategies.

PMID- 17221851
TI  - The value of sentinel lymph node biopsy in the management of head and neck
      melanoma.

PMID- 17221852
TI  - Perioperative outcomes of cytoreductive surgery and perioperative intraperitoneal
      chemotherapy for non-appendiceal peritoneal carcinomatosis from a prospective
      database.
AB  - BACKGROUND: Cytoreductive surgery combined with perioperative intraperitoneal
      chemotherapy has expanded its application in the management of peritoneal
      carcinomatosis from gastrointestinal and ovarian malignancies. An accurate
      assessment of perioperative outcomes is crucial for integration of this combined
      procedure into clinical practice. METHODS: A prospective study of 80 patients
      undergoing the combined treatment for non-appendiceal peritoneal carcinomatosis
      was conducted. Forty-seven adverse events by eight organ-systems were rated from
      Grade I to IV with increasing severity. RESULTS: One patient (1.3%) died
      postoperatively. Postoperative adverse events affected genitourinary system
      (38%), hematological system (31%), gastrointestinal system (25%), infection
      (20%), intravenous catheters status (15%), pulmonary system (14%), cardiovascular
      system (11%) and neurological system (4%). Thirty-six patients (45%) experienced
      49 Grade III adverse events. Six patients (8%) experienced eight Grade IV adverse
      events. More than four peritonectomy procedures (P = 0.010), and length of
      hospital stay of more than 21 days (P = 0.007) were strongly associated with
      Grade III and/or Grade IV morbidity. CONCLUSION: The morbidity and mortality
      rates after the combined treatment for non-appendiceal peritoneal carcinomatosis
      were within the acceptable range of surgical treatments for other
      gastrointestinal cancers. A standardized prospective database is required for an
      accurate assessment of perioperative outcomes.

PMID- 17221853
TI  - Effects of salts on protein-surface interactions: applications for column
      chromatography.
AB  - Development of protein pharmaceuticals depends on the availability of high
      quality proteins. Various column chromatographies are used to purify proteins and
      characterize the purity and properties of the proteins. Most column
      chromatographies require salts, whether inorganic or organic, for binding,
      elution or simply better recovery and resolution. The salts modulate affinity of
      the proteins for particular columns and nonspecific protein-protein or protein
      surface interactions, depending on the type and concentration of the salts, in
      both specific and nonspecific manners. Salts also affect the binding capacity of
      the column, which determines the size of the column to be used. Binding capacity,
      whether equilibrium or dynamic (under an approximation of a slow flow rate),
      depends on the binding constant, protein concentration and the number of the
      binding site on the column as well as nonspecific binding. This review attempts
      to summarize the mechanism of the salt effects on binding affinity and capacity
      for various column chromatographies and on nonspecific protein-protein or protein
      surface interactions. Understanding such salt effects should also be useful in
      preventing nonspecific protein binding to various containers.

PMID- 17221854
TI  - Evaluation of tunable diode laser absorption spectroscopy for in-process water
      vapor mass flux measurements during freeze drying.
AB  - The goal of this work was to demonstrate the use of Tunable Diode Laser
      Absorption Spectroscopy (TDLAS) as a noninvasive method to continuously measure
      the water vapor concentration and the vapor flow velocity in the spool connecting
      a freeze-dryer chamber and condenser. The instantaneous measurements were used to
      determine the water vapor mass flow rate (g/s). The mass flow determinations
      provided a continuous measurement of the total amount of water removed. Full load
      runs of pure water at different pressure and shelf temperature settings and a 5%
      (w/w) mannitol product run were performed in both laboratory and pilot scale
      freeze dryers. The ratio of "gravimetric/TDLAS" measurements of water removed was
      1.02 +/- 0.06. A theoretical heat transfer model was used to predict the mass
      flow rate and the model results were compared to both the gravimetric and TDLAS
      data. Good agreement was also observed in the "gravimetric/TDLAS" ratio for the
      5% mannitol runs dried in both freeze dryers. The endpoints of primary and
      secondary drying for the product runs were clearly identified. Comparison of the
      velocity and mass flux profiles between the laboratory and pilot dryers indicated
      a higher restriction to mass flow for the lab scale freeze dryer.

PMID- 17221855
TI  - Circulatory transport and capillary-tissue exchange as determinants of the
      distribution kinetics of inulin and antipyrine in dog.
AB  - A pharmacokinetic model was developed to estimate physiologically meaningful
      parameters of distribution kinetics from plasma concentration-time data. The
      model is based on simultaneously measured disposition curves of drug and vascular
      marker. Employing residence time distribution theory, a recirculatory model with
      two subsystems, the pulmonary and systemic circulation, was constructed. In
      addition to intravascular mixing, the axially distributed model of the systemic
      circulation accounts for transcapillary transport of solutes, quantified by
      permeability-surface area product (PS) and diffusional equilibration time.
      Parameters of ICG, inulin, and antipyrine were estimated from disposition data
      obtained in awake dogs under control conditions and during an isoproterenol
      infusion or moderate hypovolemia. Results suggest that distribution kinetics is
      (1) governed by extravascular diffusion and (2) its dependency on cardiac output
      decreases with increasing diffusional resistance. Hemorrhage decreased the
      effective PS of inulin. In conclusion, this novel mechanistic model effectively
      described both the permeability-limited distribution of inulin into interstitial
      fluid and the flow-limited distribution of antipyrine into total body water and
      might be useful for other drugs.

PMID- 17221856
TI  - Esophageal Crohn's disease treated successfully with adalimumab.

PMID- 17221857
TI  - Autofluorescence imaging colonoscopy for the diagnosis of dysplasia in ulcerative
      colitis.

PMID- 17221858
TI  - Chiral discrimination and enantioselective analysis of drugs: an overview.
AB  - Molecular recognition of different enantiomers of a drug has become of increasing
      importance in the last decade due to the racemic switch strategy adapted by the
      pharmaceutical industry. Different analytical techniques to carry out
      enantioselective analysis of chiral compounds have been suggested in the
      literature. In the following, a brief overview of different techniques used for
      enantioselective analysis is given. Challenging aspects of these techniques, such
      as the quality of analytical information received from each technique,
      advantages, and disadvantages are discussed. Alternatives (enantioselective
      membranes, amperometric biosensors, molecularly imprinted polymers (MIPs)),
      capable of meeting the requirements of industrial processes, in terms of
      productivity, cost-effectiveness, and environmental issues are critically
      reviewed.

PMID- 17221860
TI  - Merkel cell carcinoma: if no breslow, then what?

PMID- 17221859
TI  - Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal
      myopathies.
AB  - Myofibrillar myopathy (MFM) encompasses a genetically heterogeneous group of
      human diseases caused by mutations in genes coding for structural proteins of
      muscle. Mutations in the intermediate filament (IF) protein desmin (DES), a major
      cytoskeletal component of myocytes, lead to severe forms of "desminopathy," which
      affects cardiac, skeletal, and smooth muscle. Most mutations described reside in
      the central alpha-helical rod domain of desmin. Here we report three novel
      mutations--c.1325C>T (p.T442I), c.1360C>T (p.R454W), and c.1379G>T (p.S460I)-
      located in desmin's non-alpha-helical carboxy-terminal "tail" domain. We have
      investigated the impact of these and four--c.1237G>A (p.E413K), c.1346A>C
      (p.K449T), c.1353C>G (p.I451M), and c.1405G>A (p.V469M)--previously described
      "tail" mutations on in vitro filament formation and on the generation of ordered
      cytoskeletal arrays in transfected myoblasts. Although all but two mutants
      (p.E413K, p.R454W) assembled into IFs in vitro and all except p.E413K were
      incorporated into IF arrays in transfected C2C12 cells, filament properties
      differed significantly from wild-type desmin as revealed by viscometric assembly
      assays. Most notably, when coassembled with wild-type desmin, these mutants
      revealed a severe disturbance of filament-formation competence and filament
      filament interactions, indicating an inherent incompatibility of mutant and wild
      type protein to form mixed filaments. The various clinical phenotypes observed
      may reflect altered interactions of desmin's tail domain with different
      components of the myoblast cytoskeleton leading to diminished biomechanical
      properties and/or altered metabolism of the individual myocyte. Our in vitro
      assembly regimen proved to be a very sensible tool to detect if a particular
      desmin mutation is able to cause filament abnormalities.

PMID- 17221861
TI  - A surgical perspective on positron emission tomography.

PMID- 17221862
TI  - Should all patients undergoing breast conserving therapy for DCIS receive
      radiation therapy? Yes. Radiation therapy, an important component of breast
      conserving treatment for patients with ductal carcinoma in situ of the breast.

PMID- 17221863
TI  - Incidence and clinical features of X-linked Cornelia de Lange syndrome due to
      SMC1L1 mutations.
AB  - Cornelia de Lange syndrome (CdLS) is a multisystem developmental disorder
      characterized by facial dysmorphism, growth and mental retardation, microcephaly,
      and various malformations. Heterozygous mutations in the NIPBL gene have been
      detected in approximately 45% of affected individuals. Recently, a second CdLS
      gene, mapping to the X chromosome, has been identified: SMC1L1 (structural
      maintenance of chromosomes 1-like 1; or SMC1A). In order to estimate the
      incidence and refine the clinical presentation of X-linked CdLS, we have screened
      a series of 11 CdLS boys carrying no NIPBL anomaly. We have identified two novel
      de novo SMC1L1 missense mutations (c.587G>A [p.Arg196His] and c.3254A>G
      [p.Tyr1085Cys]). Our results confirm that SMC1L1 mutations cause CdLS and support
      the view that SMC1L1 accounts for a significant fraction of boys with unexplained
      CdLS. Furthermore, we suggest that SMC1L1 mutations have milder effects than
      NIPBL mutations with respect to pre- and postnatal growth retardation and
      associated malformations. If confirmed, these data may have important
      implications for directing mutation screening in CdLS.

PMID- 17221864
TI  - HbVar database of human hemoglobin variants and thalassemia mutations: 2007
      update.
AB  - HbVar (http://globin.bx.psu.edu/hbvar) is a locus-specific database (LSDB)
      developed in 2001 by a multi-center academic effort to provide timely information
      on the genomic sequence changes leading to hemoglobin variants and all types of
      thalassemia and hemoglobinopathies. Database records include extensive phenotypic
      descriptions, biochemical and hematological effects, associated pathology, and
      ethnic occurrence, accompanied by mutation frequencies and references. In
      addition to the regular updates to entries, we report significant advances and
      updates, which can be useful not only for HbVar users but also for other LSDB
      development and curation in general. The query page provides more functionality
      but in a simpler, more user-friendly format and known single nucleotide
      polymorphisms in the human alpha- and beta-globin loci are provided
      automatically. Population-specific beta-thalassemia mutation frequencies for 31
      population groups have been added and/or modified and the previously reported
      delta- and alpha-thalassemia mutation frequency data from 10 population groups
      have also been incorporated. In addition, an independent flat-file database,
      named XPRbase (http://www.goldenhelix.org/xprbase), has been developed and linked
      to the main HbVar web page to provide a succinct listing of 51 experimental
      protocols available for globin gene mutation screening. These updates
      significantly augment the database profile and quality of information provided,
      which should increase the already high impact of the HbVar database, while its
      combination with the UCSC powerful genome browser and the ITHANET web portal
      paves the way for drawing connections of clinical importance, that is from genome
      to function to phenotype.

PMID- 17221866
TI  - Low proportion of whole exon deletions causing phenylketonuria in Denmark and
      Germany.
AB  - Phenylketonuria (PKU) is an autosomal recessive genetic disorder caused by
      mutations of the gene encoding phenylalanine hydroxylase (PAH). More than 500
      different PAH mutations have been identified and about 90% of these are single
      base mutations. Although the identification rate of the PAH mutations is
      generally very high, some variants remain unidentified. A fraction of these
      mutations are the result of genomic deletions or duplications, which are not
      recognized with standard PCR-based methods. Here we present the results of exon
      deletion or duplication analysis in a total of 34 families, in which two
      mutations had not been identified using conventional diagnostic screening
      techniques. Using multiplex ligation-dependent probe amplification (MLPA), we
      found a deletion covering exon 1 and exon 2 (c.1-?_168+?del) in one patient, a
      deletion of exon 3 (c.169-?_352+?del) in four patients, and a deletion of exon 5
      (c.442-?_509+?del) in two patients. A deletion was thus detected in about 20%
      (7/34) of the families tested. Out of a combined cohort of 570 independent PKU
      patients from Denmark and Germany, exon deletions were identified in a total of
      four patients. The estimated allelic frequency of exon deletions in PKU patients
      in these two populations is therefore below 0.5%.

PMID- 17221865
TI  - MID1 mutation screening in a large cohort of Opitz G/BBB syndrome patients:
      twenty-nine novel mutations identified.
AB  - Opitz G/BBB Syndrome (OS) is a multiple congenital anomaly disorder characterized
      by defects along the body midline. The disease is characterized by variable
      expressivity of signs that include hypertelorism, cleft lip and/or palate,
      laryngo-tracheo-esophageal abnormalities, cardiac defects, and hypospadias. OS
      patients also present with mental retardation and brain anatomical abnormalities.
      An autosomal dominant form mapping to chromosome 22 and an X-linked form of OS
      are known. The gene responsible for the X-linked form of OS, MID1, codes for a
      member of the Tripartite Motif family of E3 ubiquitin ligases. Here we report 29
      novel mutations in 29 unrelated patients of a cohort of 140 male OS cases. These
      mutations are found in both familial and sporadic cases. They are scattered along
      the entire length of the gene and are represented by missense and nonsense
      mutations, insertions and deletions causing frame shift mutations, and deletion
      of either single exons or the entire gene. The variety of the mutations found
      confirms that loss-of-function is the mechanism underlying the OS phenotype.
      Moreover, the low percentage of MID1-mutated OS patients, 47% of the familial and
      13% of the sporadic cases, suggests a wider genetic heterogeneity underlying the
      OS phenotype.

PMID- 17221867
TI  - Mutation frequencies of X-linked mental retardation genes in families from the
      EuroMRX consortium.
AB  - The EuroMRX family cohort consists of about 400 families with non-syndromic and
      200 families with syndromic X-linked mental retardation (XLMR). After exclusion
      of Fragile X (Fra X) syndrome, probands from these families were tested for
      mutations in the coding sequence of 90 known and candidate XLMR genes. In total,
      73 causative mutations were identified in 21 genes. For 42% of the families with
      obligate female carriers, the mental retardation phenotype could be explained by
      a mutation. There was no difference between families with (lod score >2) or
      without (lod score <2) significant linkage to the X chromosome. For families with
      two to five affected brothers (brother pair=BP families) only 17% of the MR could
      be explained. This is significantly lower (P=0.0067) than in families with
      obligate carrier females and indicates that the MR in about 40% (17/42) of the BP
      families is due to a single genetic defect on the X chromosome. The mutation
      frequency of XLMR genes in BP families is lower than can be expected on basis of
      the male to female ratio of patients with MR or observed recurrence risks. This
      might be explained by genetic risk factors on the X chromosome, resulting in a
      more complex etiology in a substantial portion of XLMR patients. The EuroMRX
      effort is the first attempt to unravel the molecular basis of cognitive
      dysfunction by large-scale approaches in a large patient cohort. Our results show
      that it is now possible to identify 42% of the genetic defects in non-syndromic
      and syndromic XLMR families with obligate female carriers.

PMID- 17221868
TI  - Interaction geometry involving planar groups in protein-protein interfaces.
AB  - The geometry of interactions of planar residues is nonrandom in protein tertiary
      structures and gives rise to conventional, as well as nonconventional (X--H...pi,
      X--H...O, where X = C, N, or O) hydrogen bonds. Whether a similar geometry is
      maintained when the interaction is across the protein-protein interface is
      addressed here. The relative geometries of interactions involving planar
      residues, and the percentage of contacts giving rise to different types of
      hydrogen bonds are quite similar in protein structures and the biological
      interfaces formed by protein chains in homodimers and protein-protein
      heterocomplexes--thus pointing to the similarity of chemical interactions that
      occurs during protein folding and binding. However, the percentage is
      considerably smaller in the nonspecific and nonphysiological interfaces that are
      formed in crystal lattices of monomeric proteins. The C--H...O interaction
      linking the aromatic and the peptide groups is quite common in protein structures
      as well as the three types of interfaces. However, as the interfaces formed by
      crystal contacts are depleted in aromatic residues, the weaker hydrogen bond
      interactions would contribute less toward their stability.

PMID- 17221869
TI  - Crosstalk between the subunits of the homodimeric enzyme triosephosphate
      isomerase.
AB  - Homodimeric triosephosphate isomerase (TIM) from Trypanosoma cruzi (TcTIM) and T.
      brucei (TbTIM) are markedly similar in amino acid sequence and three-dimensional
      structure. In their dimer interfaces, each monomer has a Cys15 that is surrounded
      by loop3 of the adjoining subunit. Perturbation of Cys15 by methylmethane
      thiosulfonate (MMTS) induces abolition of catalysis and structural changes. In
      the two TIMs, the structural arrangements of their Cys15 are almost identical.
      Nevertheless, the susceptibility of TcTIM to MMTS is nearly 100-fold higher than
      in TbTIM. To ascertain the extent to which the characteristics of the interface
      Cys depend on the dynamics of its own monomer or on those of the adjacent
      monomer, we studied MMTS action on mutants of TcTIM that had the interface
      residues of TbTIM, and hybrids that have only one interfacial Cys15 (C15ATcTIM
      wild type TbTIM). We found that the solvent exposure of the interfacial Cys
      depends predominantly on the characteristics of the adjoining monomer. The
      maximal inhibition of activity induced by perturbation of the sole interface Cys
      in the C15ATcTIM-TbTIM hybrid is around 60%. Hybrids formed with C15ATcTIM
      monomers and catalytically inert TbTIM monomers (E168DTbTIM) were also studied.
      Their activity drops by nearly 50% when the only interfacial Cys is perturbed.
      These results in conjunction with those on C15ATcTIM-wild type TbTIM hybrid
      indicate that about half of the activity of each monomer depends on the integrity
      of each of the two Cys15-loop3 portions of the interface. This could be another
      reason of why TIM is an obligatory dimer.

PMID- 17221870
TI  - Identification of seven novel germline mutations in the human E-cadherin (CDH1)
      gene.
AB  - Hereditary diffuse gastric cancer (HDGC) is a cancer predisposition syndrome
      caused by germline mutation of the gene encoding the tumour-suppressor E-cadherin
      (CDH1). We describe the search for CDH1 mutations in 36 new diffuse gastric
      cancer families. All 16 CDH1 exons, neighbouring intronic sequence and an
      essential promoter region were screened by DNA sequencing. We detected nine
      different mutations, seven of which were novel. Of the seven novel mutations,
      five were identified in families who met the IGCLC clinical criteria for HDGC.
      Two mutations resulted in a premature stop codon and truncation of the protein.
      Three mutations affected splice sites; two of the splice-site mutations were
      shown by RT-PCR to disturb normal CDH1 splicing, while the third splice-site
      mutation was present in two unrelated HDGC families. The remaining two mutations
      resulted in amino acid substitutions and impaired the ability of E-cadherin
      protein to form cellular aggregates and suppress invasion in vitro. Together with
      the occurrence of extra-gastric tumours such as lobular breast and colorectal
      cancer, these findings further extend the types of CDH1 mutations and the
      spectrum of tumours associated with HDGC.

PMID- 17221871
TI  - A proposed molecular diagnostic flowchart for myophosphorylase deficiency
      (McArdle disease) in blood samples from Spanish patients.
AB  - McArdle disease is a metabolic myopathy due to molecular defects in the
      myophosphorylase gene (PYGM), usually diagnosed in muscle biopsy. The aims of
      this study were to characterize genetically a large series of patients and to
      establish a protocol of molecular diagnosis on blood samples. We studied 55
      Spanish unrelated patients with McArdle disease. Screening for the three more
      frequent mutations in the PYGM gene in the Spanish population (c.148C>T, p.R50X;
      c.613G>A, p.G205S; and c.2392T>C, p.W798R) were performed with polymerase chain
      reaction and restriction fragment length polymorphism (PCR-RFLP) methods. To
      identify other mutant alleles, the coding region of PYGM gene was sequenced. The
      p.R50X mutation was observed in 38 patients, the p.G205S substitution in eight,
      and the p.W798R change in nine. Nine novel mutations, five missense (c.247A>T,
      p.I83F; c.521G>A, p.G174D; c.1094C>T, p.A365V; c.1468C>T, p.R490W; and c.1730A>G,
      p.Q577R), one nonsense mutation (c.2352C>A, p.C784X), three frameshift (c.402del,
      p.N134KfsX161; c.212_218dup, p.Q73HfsX7; c.1470dup, p.R491AfsX7), and nine
      previously reported mutations were found. In addition, we also updated the
      molecular data of 95 unrelated patients with McArdle disease studied thus far in
      our center. Of these patients, 56 were either homozygous or compound heterozygous
      for the p.R50X, p.G205S, or p.W798R mutation. By including in the molecular
      diagnosis protocol sequencing of the exons 1, 14, 17 and 18 of the PYGM gene, 16
      further patients were characterized, and therefore we were able to detect the
      molecular defect in 72 out of 95 patients. A proposed molecular diagnosis
      protocol of the disease based on blood DNA would avoid muscle biopsy in 75.8%
      [95% confidence interval (95% CI): 62.1%-78.6%] of patients with McArdle disease.

PMID- 17221872
TI  - Genotype-phenotype correlations of KCNJ2 mutations in Japanese patients with
      Andersen-Tawil syndrome.
AB  - Andersen-Tawil syndrome (ATS) is a rare inherited disorder characterized by
      periodic paralysis, mild dysmorphic features, and QT or QU prolongation with
      ventricular arrhythmias in electrocardiograms (ECGs). Mutations of KCNJ2,
      encoding the human inward rectifying potassium channel Kir 2.1, have been
      identified in patients with ATS. We aimed to clarify the genotype-phenotype
      correlations in ATS patients. We screened 23 clinically diagnosed ATS patients
      from 13 unrelated Japanese families. Ten different forms of KCNJ2 mutations were
      identified in the 23 ATS patients included in this study. Their ECGs showed
      normal QTc intervals and abnormal U waves with QUc prolongation and a variety of
      ventricular arrhythmias. Especially, bidirectional ventricular tachycardia (VT)
      was observed in 13 of 23 patients (57%). Periodic paralysis was seen in 13 of 23
      carriers (57%), dysmorphic features in 17 (74%), and seizures during infancy in 4
      (17%). Functional assays for the two novel KCNJ2 mutations (c. 200G>A (p. R67Q)
      and c. 436G>A (p. G146S)) displayed no functional inward rectifying currents in a
      heterologous expression system and showed strong dominant negative effects when
      co-expressed with wild-type KCNJ2 channels (91% and 84% reduction at -50 mV
      respectively compared to wild-type alone). Immunocytochemistry and confocal
      imaging revealed normal trafficking for mutant channels. In our study, all of the
      clinically diagnosed ATS patients had KCNJ2 mutations and showed a high
      penetrance with regard to the typical cardiac phenotypes: predominant U wave and
      ventricular arrhythmias, typically bidirectional VT.

PMID- 17221873
TI  - GM1 gangliosidosis: molecular analysis of nine patients and development of an RT
      PCR assay for GLB1 gene expression profiling.
AB  - The human GLB1 gene produces two alternatively spliced transcripts that encode
      the lysosomal enzyme beta-galactosidase (GLB1) and the elastin binding protein
      (EBP). Mutations at the GLB1 locus, which are responsible for the storage
      disorder GM1 gangliosidosis, may affect either both proteins or GLB1 only. The
      EBP, when affected, contributes to specific features of GM1 gangliosidosis
      patients, such as cardiomyopathy and connective-tissue abnormalities. Here we
      report the development of reliable and quantitative assays based on real-time PCR
      for assessing the levels of GLB1 and EBP transcripts in patients' samples. We
      also report the characterisation of GLB1 gene mutations in nine GM1
      gangliosidosis patients in order to correlate the genetic lesions with mRNA
      levels and phenotypes. Mutation analysis identified four new (c.1835_1836delCC;
      p.Arg148Cys; c.1068+1G>T; and p.Pro549Leu), five known (p.Arg59His; p.Arg201His;
      p.Gly123Arg; c.245+1G>A; and c.75+2insT) mutations and one new polymorphism
      (c.1233+8T>C). Comparative analysis of the patients' phenotypes enabled a more
      thorough correlation between GLB1 mutations and specific clinical manifestations.
      GLB1 and EBP mRNA levels were both reduced in three patients carrying the
      splicing defects. The accurate and fast method for the detection of alternatively
      spliced transcripts of the GLB1 gene could be applied to other disease-causing
      lysosomal genes that encode multiple mRNAs.

PMID- 17221874
TI  - Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial
      cases and refinement of the SALL1 hot spot region.
AB  - Townes-Brocks syndrome (TBS) is an autosomal dominant malformation syndrome
      characterized by renal, anal, ear, and thumb anomalies caused by SALL1 mutations.
      To date, 36 SALL1 mutations have been described in TBS patients. All but three of
      those, namely p.R276X, p.S372X, and c.1404dupG, have been found only in single
      families thereby preventing phenotype-genotype correlations. Here we present 20
      novel mutations (12 short deletions, five short duplications, three nonsense
      mutations) in 20 unrelated families. We delineate the phenotypes and report
      previously unknown ocular manifestations, i.e. congenital cataracts with
      unilateral microphthalmia. We show that 46 out of the now 56 SALL1 mutations are
      located between the coding regions for the glutamine-rich domain mediating SALL
      protein interactions and 65 bp 3' of the coding region for the first double zinc
      finger domain, narrowing the SALL1 mutational hotspot region to a stretch of 802
      bp within exon 2. Of note, only two SALL1 mutations would result in truncated
      proteins without the glutamine-rich domain, one of which is reported here. The
      latter is associated with anal, ear, hand, and renal manifestations, indicating
      that the glutamine-rich domain is not required for typical TBS.

PMID- 17221875
TI  - Assessment of the reliability of central and peripheral fatigue after sustained
      maximal voluntary contraction of the quadriceps muscle.
AB  - The aim of the present study was to further confirm the validity of measurements
      for characterizing neuromuscular alterations by establishing their reliability
      both before and after fatigue. Thirteen men (28 +/- 5 years) volunteered to
      participate in two separate identical sessions requiring the performance of a
      sustained maximal voluntary contraction (MVC) with the quadriceps muscle for 2
      min. MVC and transcutaneous electrical stimulations were used before and
      immediately after the fatiguing contraction to investigate the reliability of MVC
      torque, central activation, and peripheral variables (M-wave properties, peak
      twitch, peak doublet) within and between sessions. Based on previous and present
      results, we advise the use of (1) voluntary activation level with potentiated
      doublet as a reference to describe central fatigue, (2) electromyographic
      activity of vastus lateralis muscle as a surrogate for quadriceps for both
      voluntary and evoked contraction, and (3) potentiated peak doublet amplitude to
      investigate contractile fatigue. These findings can be useful in the choice of
      the parameters describing central and peripheral fatigue of the quadriceps muscle
      in future studies.

PMID- 17221877
TI  - Effects of intramuscular needle position on motor unit action potential metrics.
AB  - It is unclear whether there are clinically significant differences in amplitude,
      duration, and numbers of turns and phases if an electromyographic (EMG) study is
      performed near to, or far from, the end-plate zone. The effects of temporal
      dispersion of arriving muscle-fiber action potentials on quantitative motor unit
      action potential (MUAP) metrics were assessed in simulated and biologic muscles.
      Two muscle simulation models were studied with electrode recording positions near
      the motor end-plate zone and 50-75 mm away. When the electrode was moved away
      from the end-plate zone, averages of 20 MUAPs significantly decreased in
      amplitude and area, and increased in numbers of turns and phases, but there was
      no significant change in duration. In biologic muscles (both normal and
      pathologic), similar changes in average metrics were observed, but to lesser
      degrees; few were statistically significant. Zones of innervation in biologic
      muscles are broadly distributed and, during routine electrode studies, distances
      between random electrode placements and end-plate zones are therefore relatively
      short, leading to clinically insignificant changes in quantitative MUAP metrics
      with distance from the end-plate zone. Thus, electrode position within a muscle
      is unlikely to affect clinical MUAP interpretation.

PMID- 17221876
TI  - Sensory ataxic neuropathy and esophageal achalasia in a patient with Sjogren's
      syndrome.
AB  - We describe a patient who developed an ataxic sensory syndrome associated with
      xerophthalmia and progressive dysphagia with regurgitation. Electrophysiological
      findings were consistent with an axonal sensory neuropathy, and superficial
      peroneal nerve biopsy showed a reduction in number of myelinated fibers with
      epineurial inflammation. Rheumatoid factor, anti-SSA/SSB and antinuclear
      antibodies were positive and a diagnosis of Sjogren's syndrome was made. An
      endoscopic investigation revealed esophageal achalasia. We suggest that there may
      be a common autoimmune mechanism directed to different targets on the basis of
      this rare association.

PMID- 17221878
TI  - Polyglucosan body disease myopathy: an unusual presentation.
AB  - Polyglucosan body disease (PBD) is a slowly progressive adult-onset glycogen
      storage disorder that typically affects upper and lower neurons. Myopathy, as a
      complication of PBD has been reported rarely and clinically manifests as chronic
      limb-girdle muscle weakness. We report an unusual case of PBD myopathy presenting
      as an asymmetric motor syndrome that clinically overlapped with amyotrophic
      lateral sclerosis, further expanding the phenotype of this disorder.

PMID- 17221879
TI  - The effect of eccentric exercise on position sense and joint reaction angle of
      the lower limbs.
AB  - Impaired position sense and impaired joint reaction angle of the lower limbs
      after muscle-damaging activities is a serious functional limitation that may lead
      to an increased risk of injury, particularly in older populations. The purpose of
      the present study was to examine whether position sense and joint reaction angle
      to release can be affected by eccentric exercise-induced muscle damage. Twelve
      women underwent an isokinetic exercise session of the lower limb. Isometric peak
      torque, delayed-onset muscle soreness, serum creatine kinase, position sense, and
      knee joint reaction angle to release were examined before, immediately after, and
      24, 48, and 72 h post-exercise. Due to the effect of eccentric exercise, subjects
      persistently placed their lower limb at a more extended position, representing a
      shorter knee extensor muscle. Eccentric exercise increased the knee reaction
      angle of the lower limb after release from 0 degrees and 15 degrees but not from
      30 degrees and 45 degrees . Position sense and joint reaction to release were
      similarly affected by eccentric exercise and independently of visual feedback.
      Position sense was impaired only immediately post-exercise (probably due to
      muscle fatigue), whereas impairment of the reaction angle to release persisted up
      to 3 days post-exercise (probably due to muscle damage). Attenuation of position
      sense and joint reaction angle of the lower limbs after damaging activities is a
      serious functional limitation that may lead to an increase risk of injury,
      particularly in older populations.

PMID- 17221880
TI  - Time course of axonal regeneration in acute motor axonal neuropathy.
AB  - Patients with acute motor axonal neuropathy (AMAN) generally recover well. We
      reviewed clinical and electrophysiologic recovery in 13 patients for up to 5
      years. Twelve patients showed rapid recovery over 12 months, whereas in the
      remaining one the recovery was slow and incomplete at 5 years. In AMAN, axonal
      degeneration appears to develop predominantly in the motor nerve terminals, and
      only occasionally more proximally in the nerve roots. Nerve terminal degeneration
      regeneration presumably provides a mechanism for good recovery.

PMID- 17221881
TI  - Intraepidermal nerve fiber density as a marker of early diabetic neuropathy.
AB  - The purpose of the study was to reliably identify an early stage of diabetic
      polyneuropathy (DPN) by measuring injury to epidermal nerve fibers. We compared
      intraepidermal nerve fiber density (IENFD) at the ankle and thigh of 29 diabetic
      subjects who had no clinical or electrophysiological evidence of small- or large
      fiber neuropathy to that of 84 healthy controls. The mean ankle IENFD of diabetic
      subjects was 9.1+/-5.0 mm and that of controls, 13.0+/-4.8 mm (P<0.001). The
      thigh IENFD did not differ significantly. The IENFD ratio (thigh IENFD divided by
      ankle IENFD) was 2.39+/-1.30 in diabetic subjects and 1.77+/-0.58 in controls
      (P<0.001), indicating a length-dependent reduction of IENFD in diabetics. Ankle
      IENFD remained significantly lower and the IENFD ratio higher in diabetic
      subjects after adjusting for age. Two subjects had parasympathetic dysfunction,
      two had retinopathy, and two early nephropathy. Age, height, weight, duration of
      diabetes, and average HbA1c did not influence IENFD among diabetic subjects. We
      used receiver operating characteristic (ROC) curves to describe and compare the
      utility of various threshold values of ankle IENFD and IENFD ratio for the
      diagnosis of early DPN. The sensitivity and specificity of diagnosing DPN using
      ankle IENFD of less than 10 mm were 72.4% and 76.2%, respectively. Thus,
      asymptomatic diabetics have a measurable, length-dependent reduction of distal
      epidermal nerves. Analogous to microalbuminuria in diabetic nephropathy, reliable
      identification and quantitation of nascent diabetic neuropathy may have potential
      therapeutic implications.

PMID- 17221882
TI  - Single-fiber electromyography during menstrual exacerbation and ovulatory
      suppression in MuSK antibody-positive myasthenia gravis.
AB  - We report a patient with muscle-specific tyrosine kinase (MuSK) antibody-positive
      myasthenia gravis who experienced worsening of myasthenic weakness associated
      with alterations in estrogen and progesterone levels during the administration of
      oral contraceptive therapy. Single-fiber electromyography was performed to
      document changes in neuromuscular transmission associated with the clinical
      exacerbation and subsequent resolution of the menstrual exacerbation and clinical
      improvement experienced with continuous monophasic oral contraceptive therapy.
      The potential long-term benefit of ovulatory suppression in MuSK antibody
      positive myasthenia gravis is discussed.

PMID- 17221883
TI  - Motor cortex abnormalities in amyotrophic lateral sclerosis with transcranial
      direct-current stimulation.
AB  - The aim of this study was to identify a neurophysiological marker of upper
      motoneuron involvement in patients with sporadic amyotrophic lateral sclerosis
      (ALS). For this purpose we evaluated the after-effects of transcranial direct
      current stimulation (tDCS) on excitability of the motor cortex of eight ALS
      patients and eight healthy controls. Healthy controls showed a transient polarity
      specific change in corticospinal excitability of about +/-45%, with anodal tDCS
      inducing facilitation and cathodal tDCS leading to inhibition, whereas no change
      could be induced in ALS patients after either type of tDCS. It is likely that the
      lack of tDCS after-effects in ALS is the result of alterations of the
      motoneuronal membrane or, alternatively, may represent an electrophysiological
      correlate of disordered glutamate neurotransmission. Further studies are
      warranted to confirm these results. The present findings may lead to a new,
      reliable electrophysiological marker of upper motoneuronal involvement in ALS.

PMID- 17221884
TI  - Fibrillation potentials following spinal cord injury: improvement with
      neurotrophins and exercise.
AB  - Fibrillation potentials and positive sharp waves (spontaneous potentials) are the
      electrophysiological hallmark of denervated skeletal muscle, and their detection
      by intramuscular electromyography (EMG) is the clinical gold standard for
      diagnosing denervated skeletal muscle. Surprisingly, spontaneous potentials have
      been described following human and experimental spinal cord injury (SCI) in
      muscles innervated by spinal cord segments distal to the level of direct spinal
      injury. To determine whether electrophysiological abnormalities are improved by
      two therapeutic interventions for experimental SCI, neurotrophic factors and
      exercise training, we studied four representative hindlimb muscles in adult
      domestic short-hair cats following complete transection of the spinal cord at T11
      T12. In untreated cats, electrophysiological abnormalities persisted unchanged
      for 12 weeks postinjury, the longest duration studied. In contrast, fibrillations
      and positive sharp waves largely resolved in animals that underwent weight
      supported treadmill training or received grafts containing fibroblasts
      genetically modified to express brain-derived neurotrophic factor and
      neurotrophin-3. These findings suggest that neurotrophins and activity play an
      important role in the poorly understood phenomenon of fibrillations distal to
      SCI.

PMID- 17221885
TI  - NMR structure of YcgL, a conserved protein from Escherichia coli representing the
      DUF709 family, with a novel alpha/beta/alpha sandwich fold.

PMID- 17221886
TI  - Prediction of volumetric productivity of an outdoor photobioreactor.
AB  - Volumetric productivity of Monodus subterraneus cultivated in an outdoor pilot
      plant bubble column was predicted with a mathematical model. Two border cases to
      model the photobioreactor were chosen. Firstly, a model with no light integration
      in which it is assumed that microalgae can adapt immediately to local light
      conditions. Secondly, full light integration implicating that microalga can
      convert all absorbed light with a photosynthetic yield based on average light
      intensity. Because temperature and light conditions in our photobioreactor
      changed during the day, photosynthetic yields at any combination of temperature
      and light intensity were needed. These were determined in repeated-batch lab
      scale experiments with an experimental design. The model was evaluated in an
      outdoor bubble column at different natural light conditions and different
      temperatures. Volumetric productivities in the bubble column were predicted and
      compared with experimental volumetric productivities. The light integration model
      over-estimated productivity, while the model in which we assumed no light
      integration under-estimated productivity. Light integration occurred partly (47%)
      during the period investigated. The average observed biomass yield on light was
      0.60 g.mol(-1). The model of partly light integration predicted an average
      biomass yield on light of 0.57 g.mol(-1) and predicted that productivity could
      have been increased by 19% if culture temperature would have been maintained at
      24 degrees C.

PMID- 17221887
TI  - Design of highly efficient cellulase mixtures for enzymatic hydrolysis of
      cellulose.
AB  - An extremely highly active cellobiohydrolase (CBH IIb or Cel6B) was isolated from
      Chrysosporium lucknowense UV18-25 culture filtrate. The CBH IIb demonstrated the
      highest ability for a deep degradation of crystalline cellulose amongst a few
      cellobiohydrolases tested, including C. lucknowense CBH Ia, Ib, IIa, and
      Trichoderma reesei CBH I and II. Using purified C. lucknowense enzymes (CBH Ia,
      Ib, and IIb; endoglucanases II and V; beta-glucosidase, xylanase II), artificial
      multienzyme mixtures were reconstituted, displaying an extremely high performance
      in a conversion of different cellulosic substrates (Avicel, cotton, pretreated
      Douglas fir wood) to glucose. These mixtures were much or notably more effective
      in hydrolysis of the cellulosic substrates than the crude multienzyme C.
      lucknowense preparation and other crude cellulase samples produced by T. reesei
      and Penicillium verruculosum. Highly active cellulases are a key factor in
      bioconversion of plant lignocellulosic biomass to ethanol as an alternative to
      fossil fuels.

PMID- 17221888
TI  - Natural cellulose fibers from switchgrass with tensile properties similar to
      cotton and linen.
AB  - We report the production and characteristics of natural cellulose fibers obtained
      from the leaves and stems of switchgrass. In this paper, the composition,
      structure and properties of fibers obtained from the leaves and stem of
      switchgrass have been studied in comparison to the common natural cellulose
      fibers, such as cotton, linen and kenaf. The leaves and stems of switchgrass have
      tensile properties intriguingly similar to that of linen and cotton,
      respectively. Fibers were obtained from the leaves and stems of switchgrass using
      a simple alkaline extraction and the structure and properties of the fibers were
      studied. Fibers obtained from switchgrass leaves have crystallinity of 51%,
      breaking tenacity of 5.5 g per denier (715 MPa) and breaking elongation of 2.2%
      whereas the corresponding values for fibers obtained from switchgrass stems are
      46%, 2.7 g per denier and 6.8%, respectively. Switchgrass is a relatively easy to
      grow and high yield biomass crop that can be source to partially substitute the
      natural and synthetic fibers currently in use. We hope that this research will
      stimulate interests in using switchgrass as a novel fiber crop in addition to
      being promoted as a potential source for biofuels.

PMID- 17221889
TI  - Exploiting the pressure effect on lipase-catalyzed wax ester synthesis in dense
      carbon dioxide.
AB  - The present work focuses on the thermodynamic interpretation of the lauryl oleate
      biosynthesis in high-pressure carbon dioxide. Lipase-catalyzed lauryl oleate
      production by oleic acid esterification with 1-dodecanol over immobilized lipase
      from Rhizomucor miehei (Lipozyme RM IM) was successfully performed in a sapphire
      window batch stirred tank reactor (BSTR) using dense CO(2) as reaction medium.
      The experiments were planned to elucidate the pressure effect on the reaction
      performance. With increasing the pressure up to 10 MPa, the catalytic efficiency
      of the studied enzyme improved rising up to a maximum and decreased at higher
      pressure values. Kinetic observations, exhibiting that dense CO(2) expanded
      reaction mixture in subcritical conditions led to higher performance than when
      diluted in a single supercritical phase, were elucidated by phase-equilibrium
      arguments. The experimental results were justified with emphasis on thermodynamic
      interpretation of the studied system. Particularly, the different reaction
      performances obtained were related to the position of the operating point with
      respect to the location of liquid-vapor phase boundaries of the reactant fatty
      acid/alcohol/CO(2) ternary system. The outlook for exploitation of CO(2) expanded
      phase at lower pressure compared to supercritical phase, with heterogeneous
      system in which the solid catalyst particles are exposed to dense CO(2) expanded
      reaction mixture, in developing new biotransformation schemes is promising.

PMID- 17221890
TI  - Dibutyl phthalate biodegradation by the white rot fungus, Polyporus brumalis.
AB  - In this study, white rot fungus, Polyporus brumalis, was applied to degrade
      dibutyl phthalate (DBP), a major environmental pollutant. The degradation
      potential and resulting products were evaluated with HPLC and GC/MS. As DBP
      concentration increased to 250, 750, and 1,250 microM, the mycelial growth of P.
      brumalis was inhibited. However, growth was still observed in the 1,250 microM
      concentration. DBP was nearly eliminated from culture medium of P. brumalis
      within 12 days, with 50% of DBP adsorbed by the mycelium. Diethyl phthalate (DEP)
      and monobutyl phthalate (MBP) were detected as intermediate degradation products
      of DBP. In culture medium, the concentration of DEP was higher than that of MBP
      during the incubation period. After 12-15 days, the concentrations of both
      decreased rapidly in the culture medium. The primary final degradation product of
      DBP in culture medium was phthalic acid anhydride, as well as trace amounts of
      aromatic compounds, such as alpha-hydroxyphenylacetic acid, benzyl alcohol, and O
      hydroxyphenylacetic acid. According to these results, the degradation of DBP in
      culture medium by the white rot fungus, P. brumalis, may be completed through two
      pathways-transesterification and de-esterification-which successively combine
      into an intracellular degradation pathway.

PMID- 17221891
TI  - Exceptional affinity of nanostructured organic-inorganic hybrid materials towards
      dioxygen: confinement effect of copper complexes.
AB  - We report the exceptional reactivity towards dioxygen of a nanostructured organic
      inorganic hybrid material due to the confinement of copper cyclam within a silica
      matrix. The key step is the metalation reaction of the ligand, which can occur
      before or after xerogel formation through the sol-gel process. The incorporation
      of a Cu(II) center into the material after xerogel formation leads to a bridged
      Cu(I)/Cu(II) mixed-valence dinuclear species. This complex exhibits a very high
      affinity towards dioxygen, attributable to auto-organization of the active
      species in the solid. The remarkable properties of these copper complexes in the
      silica matrix demonstrate a high cooperative effect for O(2) adsorption; this is
      induced by close confinement of the two copper ions leading to end-on mu
      eta(1):eta(1)-peroxodicopper(II) complexes. The anisotropic packing of the
      tetraazamacrocycle in a lamellar structure induces an exceptional reactivity of
      these copper complexes. We show for the first time that the organic-inorganic
      environment of copper complexes in a silica matrix fully model the protecting
      role of protein in metalloenzymes. For the first time an oxygenated dicopper(II)
      complex can be isolated in a stable form at room temperature, and the reduced
      Cu(2) (I,I) species can be regenerated after several adsorption-desorption
      cycles. These data also demonstrate that the coordination scheme and reactivity
      of the copper cyclams within the solid are quite different from that observed in
      solution.

PMID- 17221892
TI  - Functionalized 3D oligothiophene dendrons and dendrimers--novel macromolecules
      for organic electronics.

PMID- 17221893
TI  - Controlled release of guest molecules from mesoporous silica particles based on a
      pH-responsive polypseudorotaxane motif.

PMID- 17221895
TI  - A general method for measurement of enantiomeric excess by using electrooptics in
      ferroelectric liquid crystals.

PMID- 17221894
TI  - A site- and stereoselective intermolecular alkene-alkyne coupling process.

PMID- 17221896
TI  - Small but effective: copper hydride catalyzed synthesis of alpha-hydroxyallenes.

PMID- 17221897
TI  - High-pressure synthesis of crystalline carbon nitride imide, C2N2(NH).

PMID- 17221898
TI  - Stereochemical and mechanistic investigations of a palladium-catalyzed annulation
      of secondary alkyl iodides.

PMID- 17221899
TI  - Crystalline Mo3VOx mixed-metal-oxide catalyst with trigonal symmetry.

PMID- 17221900
TI  - Direct synthesis of polymer nanocapsules with a noncovalently tailorable surface.

PMID- 17221901
TI  - Thin films composed of multiwalled carbon nanotubes, gold nanoparticles and
      myoglobin for humidity detection at room temperature.
AB  - Optically transparent and electrically conductive nanocomposite thin films
      consisting of multiwalled carbon nanotubes (MWCNTs), gold nanoparticles (GNPs)
      and myoglobin molecules that glue GNPs and MWCNTs together are fabricated for the
      first time on glass substrates from aqueous solution. The nanocomposite thin film
      is capable of varying its resistance, impedance or optical transmittance at room
      temperature in response to changes in ambient humidity. The conductometric
      sensitivity to relative humidity (RH) of the nanocomposite thin film is compared
      with those of the pure and Mb-functionalized MWCNT layers. The pure MWCNT layer
      shows a small increase in its resistance with increasing RH due to the effect of
      p-type semiconducting nanotubes present in the film. In contrast, a four times
      higher sensitivity to RH is observed for both the nanocomposite and Mb
      functionalized MWCNT thin films. The sensitivity enhancement is attributable to
      swelling of the thin films induced by water absorption in the presence of Mb
      molecules, which increases the inter-nanotube spacing and thereby causes a
      further increase of the film resistance. A humidity change as low as DeltaRH=0.3
      % has been readily detected by conductometry using the nanocomposite thin film.

PMID- 17221902
TI  - Geometry dependence of spin-spin couplings in cyanamide by DFT analysis.
AB  - There have been numerous theoretical and experimental investigations examining
      NMR parameters related to non-amino N-H...N H-bonded moieties in both biological
      and chemical contexts. In contrast, little information on the geometry dependence
      of NMR parameters related to the biologically important H-bond donor amino group
      is available. Herein, the geometric dependencies of the one-bond amino N-H spin
      spin coupling constants [(1)J(NH)] in the cyanamide monomer and dimer have been
      computed with B3LYP and the aug-cc-pVTZ-su0 basis set. In an isolated planar
      cyanamide molecule, the |(1)J(NH)| couplings were found to increase as the N-H
      bond lengthened. In contrast, in the planar cyanamide dimer the size of the H
      bonded amino N-H coupling (|(1)J(N(d)H(d))|) decreased with increasing N(d)H(d)
      bond length. The |(1)J(N(d)H(d))| coupling was larger than the
      |(1)J(N(d)H(free))| coupling for N(d)H(d) distances up to 1.18 A (for a fixed
      N(d)H(free) distance of 1.006 A). Hence, the decrease of |(1)J(NH)| with
      increasing N-H distance, as well as the larger value of |(1)J(N(d)H(d))| compared
      to |(1)J(N(d)H(free))|, were only observed for situations where the amino group
      is involved in an H-bonding interaction. This is attributed to electron
      redistribution induced by the presence of the second cyanamide molecule. Similar
      electron-redistribution effects are thought to be responsible for the observed
      distance dependence of computed (1)J(NH) couplings of H-bonded amino groups in
      near-planar G-quartet structures. Here, the |(1)J(NH)| couplings of the amino N-H
      bonds decreased with increasing N-H bond length whereas the |(1)J(N(d)H(d))|
      couplings are approximately 7 Hz larger than the |(1)J(N(d)H(free))| couplings,
      despite the longer N(d)-H(d) bond length.

PMID- 17221903
TI  - Controlling the electrons provides means for controlling chemistry.

PMID- 17221904
TI  - Oriented growth of single-crystalline Bi2S3 nanowire arrays.

PMID- 17221905
TI  - Complete 1H and 13C NMR assignments of the epimeric menthane-1-carboxylic acids.
AB  - Complete NMR analyses with full assignments for (1)H and (13)C NMR spectral data
      for both epimers of menthane-1-carboxylic acid are described. The NMR properties
      of the recently synthesized axial isomer had not been previously described, and
      through use of a variety of 1D and 2D techniques, additional information is
      provided for the equatorial isomer. As well as assignments of chemical shifts,
      homonuclear coupling constants were determined for the equatorial isomer and most
      of coupling constants were measured for the axial isomer.

PMID- 17221906
TI  - Semi-micro column high-performance liquid chromatography with UV detection for
      quantification of aspirin and salicylic acid and its application to patients'
      sera administered with low-dose enteric-coated aspirin.
AB  - A simultaneous determination of aspirin (ASA) and its metabolite, salicylic acid
      (SA), in human serum by a semi-micro column HPLC-UV was developed. A relatively
      small size of serum sample (100 microL) containing ASA and SA was cleaned up by a
      simple solid phase extraction. A good separation of ASA and SA could be achieved
      within 25 min using a semi-micro ODS column with an eluent of MeOH/0.7 mm
      phosphoric acid solution (pH 2.5) = 50:50 (v/v). The calibration curves for ASA
      and SA showed good linearity (r = 0.999) with the detection limits 114 and 38
      ng/mL at a signal-to-noise ratio of 3, respectively. ASA and SA in patients' sera
      administered with low-dose enteric-coated aspirin were determined, and the
      concentration ranges obtained for ASA and SA were 1.2-2.2 and 0.5-57.3 microg/mL,
      respectively.

PMID- 17221907
TI  - A solid-phase extraction method for high-performance liquid chromatographic
      determination of salvianolic acid B in rabbit plasma: application to
      pharmacokinetic study.
AB  - A sensitive solid-phase extraction/high-performance liquid chromatographic method
      with ultraviolet detection was established for the analysis of salvianolic acid B
      in rabbit plasma. The analyte was separated on a reversed-phase column with
      trifluoroacetic acid-methanol-acetonitrile (70:10:20, v/v/v) as mobile phase at a
      flow rate of 1 mL/min, and ultraviolet detection at 315 nm. The calibration curve
      for salvianolic acid B was linear over the range 35-1400 microg/L with
      coefficients of correlation >0.999. The inter-day and intra-day precisions of
      analysis were <15%, and assay accuracy ranged from 95.3 to 109.1%. This method is
      suitable for determining salvianolic acid B in plasma and thus investigating the
      pharmacokinetics of salvianolic acid B.

PMID- 17221908
TI  - Quantification of fexofenadine in human plasma by liquid chromatography coupled
      to electrospray tandem mass spectrometry using mosapride as internal standard.
AB  - A rapid high-performance liquid chromatography/positive ion electrospray tandem
      mass spectrometry method was developed and validated for the quantification of
      fexofenadine in human plasma using mosapride as internal standard. Following
      solid-phase extraction, the analytes were separated using an isocratic mobile
      phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction
      monitoring mode using the respective [M+H]+ ions, m/z 502/466 for fexofenadine
      and m/z 422/198 for the IS. The method exhibited a linear dynamic range of 1-500
      ng/mL for fexofenadine in human plasma. The lower limit of quantification was 1
      ng/mL with a relative standard deviation of less than 5% for fexofenadine.
      Acceptable precision and accuracy were obtained for concentrations over the
      standard curve range. The total chromatographic run time of 2 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- 17221909
TI  - An improved high-throughput liquid chromatographic/tandem mass spectrometric
      method for terbinafine quantification in human plasma, using automated liquid
      liquid extraction based on 96-well format plates.
AB  - A fully automated high-throughput liquid chromatography/tandem mass spectrometry
      (LC-MS/MS) method was developed for terbinafine quantification in human plasma.
      The plasma samples were treated by liquid-liquid extraction (LLE) in 2.2 mL 96
      deepwell plates. Terbinafine and the internal standard (IS) N-methyl-1
      naphthalenemethylamine were extracted from human plasma by LLE, using a mixture
      of methyl t-butyl ether (MTBE)-hexane (70:30, v/v) as the organic solvent. All
      liquid transfer steps, including preparation of calibration standards and quality
      control samples, as well as the addition of the IS, were performed automatically
      by using robotic liquid handling workstations. After vortexing, centrifugation
      and freezing, the supernatant organic solvent was evaporated and reconstituted in
      a small volume of a reconstitution solution. Sample analysis was performed by
      reversed-phase LC-MS/MS, with positive ion electrospray ionization, using
      multiple reaction monitoring (MRM). The method had a very short sample
      preparation time and a chromatographic run time of 2.2 min. It was proved to have
      excellent sensitivity, specificity, accuracy as well as inter- and intraday
      precision for the quantification of terbinafine in human plasma. The calibration
      curve was linear for the range of concentrations 5.0-2000.0 ng/mL. The proposed
      method was applied to the rapid and reliable determination of terbinafine in a
      bioequivalence study after per os administration of 250 mg tablet formulations of
      terbinafine.

PMID- 17221910
TI  - Rapid identification of Helicobacter pylori by capillary electrophoresis: an
      overview.
AB  - Helicobacter pylori can cause gastritis and peptic ulcers and is directly
      associated with the development of gastric cancer. There are many types of
      diagnostic methods used to identification H. pylori (invasive and non-invasive),
      but these methods usually require time-consuming and laborious procedures and
      therefore are not capable of fast diagnosis in cases of emergency. This
      contribution describes the new achievements, interdisciplinary significance and
      some future directions in the application of capillary electrophoresis for
      determination of H. pylori.

PMID- 17221911
TI  - A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method for the estimation of amlodipine in human plasma.
AB  - A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS)
      method has been developed and validated for the estimation of amlodipine in human
      plasma. Amlodipine was extracted from human plasma by using a solid-phase
      extraction technique. Imipramine was used as the internal standard. A Hypersil
      BDS C18 column provided chromatographic separation of analytes followed by
      detection with mass spectrometry. The method involves a rapid solid-phase
      extraction from plasma, simple isocratic chromatography conditions and mass
      spectrometric detection that enables detection at sub-nanogram levels. The
      proposed method has been validated for a linear range of 0.1-10.0 ng/mL with
      correlation coefficient >or=0.9990. The intrarun and interrun precision and
      accuracy were within 10.0%. The overall recovery for amlodipine was 63.67%. Total
      run time was 3.2 min only.

PMID- 17221912
TI  - Development of a LC-ESI/MS/MS assay for the quantification of vanillin using a
      simple off-line dansyl chloride derivatization reaction to enhance signal
      intensity.
AB  - Vanillin is responsible for producing the familiar smell of vanilla. Vanillin has
      many similarities with other flavor phenolic compounds and could potentially show
      similar pharmacological activity. A previously published analytical method was
      adapted, developed and tested. Vanillin was extracted from rat plasma using
      protein precipitation with acetone. Prior to LC-ESI/MS/MS analysis, an aliquot of
      the supernatant was used to proceed to the derivatization of vanillin and the
      internal standard with dansyl chloride to enhance signal intensity in positive
      electrospray mode. The chromatography was performed on a 100 x 2.1 mm C8 column
      and an isocratic mobile phase composed of 75:25 acetonitrile:0.5% formic acid in
      water with a flow rate fixed at 500 microL/min. A linear (weighted
      1/concentration) relationship was used to perform the calibration over an
      analytical range of 10-10,000 ng/mL. The intra-batch precision and accuracy at
      the limit of quantitation (10 ng/mL), medium (500 ng/mL) and high (10,000 ng/mL)
      concentrations were 10.7, 7.0 and 7.2% and 103.5, 108.0 and 100.1%, respectively.
      The observed recovery was greater than 87% and no significant ionization
      suppression or matrix effect was observed. This LC-ESI/MS/MS method for the
      determination of vanillin in rat plasma provided results within generally
      accepted criteria used for bioanalytical assay.

PMID- 17221913
TI  - A liquid chromatography-mass spectrometry assay method for simultaneous
      determination of amiodarone and desethylamiodarone in rat specimens.
AB  - A liquid chromatographic-mass spectrometry (LC/MS) assay method was developed for
      the determination of amiodarone and desethylamiodarone in rat specimens. Analytes
      were extracted using liquid-liquid extraction in hexane. The LC/MS system
      consisted of a Waters Micromass ZQtrade mark 4000 spectrometer with an
      autosampler and pump. A C(18) 3.5 microm (2.1 x 50 mm) column heated to 45
      degrees C was used for separation. The mobile phase consisted of methanol and
      0.2% aqueous formic acid pumped at 0.2 mL/min as a linear gradient. Components
      eluted within 12 min. The concentrations of ethopropazine (internal standard),
      desethylamiodarone and amiodarone were monitored for m/z of 313.10, combination
      of 546.9 and 617.73, and 645.83, respectively. In plasma (0.1 mL), linearity was
      achieved between the peak area ratios and concentrations over the range of 2.5
      1000 ng/mL for both amiodarone and desethylamiodarone (r(2) > 0.999). The
      intraday and interday CV were equal or less than 18%, and mean error was <12%.
      Similarly, in homogenates containing 0.1 g of rat tissue, linearity was observed
      in standards ranging from 5 to 5000 ng/g. The method was successfully used to
      measure tissue and plasma concentrations of drug. The validated lower limit of
      quantitation was 2.5 ng/mL for drug and metabolite, based on 0.1 mL of plasma.

PMID- 17221914
TI  - Determination of gambogic acid in dog plasma by high-performance liquid
      chromatography for a pharmacokinetic study.
AB  - A rapid, simple and sensitive high-performance liquid chromatography method for
      the quantification of gambogic acid in dog plasma was developed and validated.
      After acidification with hydrochloric acid, dog plasma was extracted with ethyl
      acetate and determined by HPLC. The analysis was carried out on a reversed-phase
      C(18) analytical column. The mobile phase consisted of a mixture of methanol
      0.05% phosphoric acid (94:6, v/v), and the column temperature was maintained at
      35 degrees C. A constant mobile phase flow rate of 1.0 mL/min was employed
      throughout the analyses. The ultraviolet detector was set at 360 nm.
      Chromatographic separation was achieved in less than 10 min and the calibration
      curve was linear over a concentration range of 0.156-20 microg/mL. The intra
      assay and inter-assay variability values were less than 10.0%. The accuracy
      ranged from 93.0 to 104.2%. The established method has been successfully applied
      to a pharmacokinetic study of gambogic acid in dogs.

PMID- 17221915
TI  - Determination of N-methyl-4-isoleucine-cyclosporin (NIM811) in human whole blood
      by high performance liquid chromatography-tandem mass spectrometry.
AB  - A liquid chromatographic method with tandem mass spectrometric detection (LC
      MS/MS) for the determination of N-methyl-4-isoleucine-cyclosporin (NIM811) was
      developed and validated over the concentration range 1-2500 ng/mL in human whole
      blood using a 0.05 mL sample volume. NIM811 and the internal standard, d(12)
      cyclosporin A (d(12)-CsA), were extracted from blood using MTBE via liquid-liquid
      extraction. After evaporation of the organic solvent and reconstitution, a 10
      microL aliquot of the resulting extract was injected onto the LC-MS/MS system.
      Chromatographic separation of NIM811 and internal standard was performed using a
      Waters Symmetry RP-8 (50 x 4.6 mm, 3 microm particle size) column. The mobile
      phase consists of 10 mm ammonium acetate in water (A) and acetonitrile (B), with
      45% B from 0 to 0.2 min, 45 to 85% B from 0.2 to 0.8 min and 85% B from 0.8 to
      2.2 min. The total run time was 3.5 min with a flow rate of 0.8 mL/min. The
      method was validated for sensitivity, linearity, reproducibility, stability,
      dilution integrity and recovery. The precision and accuracy of quality control
      samples at low (2.00 ng/mL), medium (20.0 and 400 ng/mL) and high (2000 ng/mL)
      concentrations were in the range 1.1-4.3% relative standard deviation (RSD) and 
      2.5-10.0% (bias), respectively, from three validation runs. The method has been
      used to measure the exposure of NIM811 in human subjects.

PMID- 17221916
TI  - The lipophilicity estimation of 5-arylidene derivatives of (2-thio)hydantoin with
      antimycobacterial activity.
AB  - The lipophilicity of antituberculotic 5-arylidene derivatives of (thio)hydantoin,
      thioacetazone and isoniazid has been determined by reversed-phase thin-layer
      chromatography (RP-TLC). Mixtures of acetone and water (with acetone content 60
      85%) were used as the mobile phase. The R(M) (relative lipophilicity) of each
      compound (except isoniazid) decreased linearly with the increasing concentration
      of acetone. The partition coefficients (log P) of the compounds were calculated
      by the use of eight computer programs (ClogP, KowWin, XlogP, AlogPs, CAChe,
      Pallas, Interactive analysis and Slipper) and compared with the experimental
      lipophilicity (R(M0)). According to the observations the best tools for in silico
      predicting log P of (2-thio)hydantoins are programs KowWin and AlogPs.

PMID- 17221917
TI  - Bifurcated hydrogen-bonding effect on the shielding and coupling constants in
      trifluoroacetyl pyrroles as studied by 1H, 13C and 15N NMR spectroscopy and DFT
      calculations.
AB  - According to the (1)H, (13)C and (15)N NMR spectroscopic data and DFT
      calculations, bifurcated N--H...N and N--H...O intramolecular hydrogen bond is
      shown to be present in 2-trifluoroacetyl-5-(2'-pyridyl)-pyrrole. This bifurcated
      hydrogen bond causes an increase in the absolute size of the (1)J(N,H) coupling
      constant by about 6 Hz, and the deshielding of the bridge proton by 2 ppm. DFT
      calculations show that the influence of the N--H...N and N--H...O intramolecular
      hydrogen bonds on the (1)J(N,H) coupling and proton shielding is almost additive,
      although the components of the bifurcated hydrogen bond slightly weaken each
      other. In 2-trifluoroacetyl-5-(2'-pyridyl)-pyrrole, the coupling constants
      involving the fluorine and the N--H covalent bond nuclei depend dramatically on
      the spatial position of the pyridine ring. The pyridine ring rotation operates as
      a quantum switch controlling the spin information transfer between the (19)F and
      (15)N nuclei, as well as the proton.

PMID- 17221918
TI  - Complete 1H and 13C NMR assignments of sesquiterpene glucosides from Ixeris
      sonchifolia.
AB  - Four sesquiterpene glucosides were isolated from Ixeris sonchifolia Hance. The
      structure of a new compound (1) was assigned as 9beta-monohydroxy-2,12-dioxo
      guaia-3,11(13)-dien-1alpha,5alpha,6beta,7alpha,9beta,10alphaH-12,6-olide-9-O-beta
      D- glucopyranoside (ixerinoside). In addition, unambiguous and complete
      assignments of (1)H NMR chemical shifts for crepidiaside A (2), ixerin Z (3), and
      11,13alpha-dihydroixerin Z (4) are presented. The assignments were achieved by
      two-dimensional NMR (gCOSY, gHSQC, gHMBC, NOESY) and one-dimensional nuclear
      Overhauser effect (NOE) experiments.

PMID- 17221919
TI  - Simultaneous determination of metformin and glipizide in human plasma by liquid
      chromatography-tandem mass spectrometry.
AB  - A method has been developed for the simultaneous quantification of metformin (I)
      and glipizide (II) in human plasma. It is based on high-performance liquid
      chromatography with electrospray ionization tandem mass (LC-ESI-MS/MS)
      spectrometric detection in positive ionization mode. Phenformin (III) and
      gliclazide (IV) were used as internal standards for I and II, respectively. The
      MS/MS detection was performed in multiple reaction monitoring (MRM) mode. The
      precursor-product ion combinations of m/z 130 --> 71, 446 --> 321, 206 --> 60 and
      324 --> 127 were used to quantify I, II, III and IV, respectively. This method
      was validated in the concentration ranges of 0.02-4 microg/mL for I and 0.004-0.8
      microg/mL for II. It was utilized to support a clinical pharmacokinetic study
      after single dose oral administration of a combination of I and II.

PMID- 17221920
TI  - A high-performance liquid chromatographic method for determination of mitragynine
      in serum and its application to a pharmacokinetic study in rats.
AB  - A simple HPLC technique for determining mitragynine levels in serum was
      developed. The separation system consisted of a C18 column heated to 35 degrees
      C, a methanol-water (80:20, v/v) mobile phase, a flow rate of 0.8 mL/min and
      detection in the ultraviolet at 225 nm. Mitragynine, with a retention time of
      10.09 min, was well resolved from any interferences in human serum and the
      internal standard peak. The calibration curve was linear from 0.1 to 10 microg/mL
      (r = 0.9995). Extraction of mitragy-nine from alkalinized serum using diethyl
      ether gave a high recovery (>or=85%). The intra- and inter-day precisions of the
      method were 4.29-5.88%RSD and 7.06-8.45%RSD, respectively. The accuracy ranged
      from -9.54 to +0.67%DEV. The limit of detection was 0.03 microg/mL and the lower
      limit of quantification was 0.1 microg/mL. Mitragynine in the stock solution was
      stable during 30 days of storage at 4 degrees C. This method was successfully
      applied to determine the pharmacokinetic characteristics of mitragynine levels in
      the serum of rats after it was administered orally.

PMID- 17221921
TI  - Development and validation of high-performance liquid chromatography-tandem mass
      spectrometry assay for 6-(3-benzoyl-ureido)-hexanoic acid hydroxyamide, a novel
      HDAC inhibitor, in mouse plasma for pharmacokinetic studies.
AB  - A liquid chromatography/tandem mass spectrometric method for the quantification
      of 6-(3-benzoyl-ureido)-hexanoic acid hydroxyamide (EX-2), a novel histone
      deacetylase (HDAC) inhibitor, in mouse plasma was developed to support in-house
      pharmacokinetic (PK) studies in the lead optimization stage. In order to
      determine the PK parameters for EX-2 in comparison to other HDAC inhibitors such
      as suberoylanilide hydroxamic acid (SAHA), PXD-101 and LBH-589, which are
      currently in different stages of clinical trials, research-grade bio-analytical
      method validations were carried out for EX-2 and these reference HDAC inhibitors,
      which were synthesized by in-house medicinal chemists. The components of
      validation consisted of specificity, extraction efficiency, signal-response of
      calibration standards, lower limit of quantification, autosampler stability and
      accuracy and precision of quality control samples. The validated LC/MS/MS methods
      were accurate and precise. The calibration curve ranged from 1 to 1600 ng/mL for
      all the analytes. The methods developed were used to quantify EX-2 and other HDAC
      inhibitors in mouse plasma obtained from pharmacokinetic studies. The results
      suggest that EX-2 has better PK parameters compared with the reference drugs and
      is a promising drug development candidate.

PMID- 17221922
TI  - In vivo evaluation of CYP1A2, CYP2A6, NAT-2 and xanthine oxidase activities in a
      Greek population sample by the RP-HPLC monitoring of caffeine metabolic ratios.
AB  - A RP-HPLC method was developed for the assessment of caffeine and its metabolites
      in urine and was used for the evaluation of the CYP1A2, CYP2A6, xanthine oxidase
      (XO) and N-acetyl-transferase-2 (NAT-2) in vivo activities in 44 Greek volunteers
      (21 men, 23 women). Spot urine samples were analyzed 6 h after 200 mg caffeine
      consumption, following a 30 h methylxantine-free diet. The major urinary caffeine
      metabolites are 1-methyluric acid (1U), 5-acetylamino-6-formylamino-3
      methyluracil (AFMU), 1-methylxanthine (1X), 1,7-dimethyluric acid (17U) and 1,7
      dimethylxanthine (17X). CYP1A2, CYP2A6, XO and NAT-2 activities were estimated
      from the metabolic ratios (AFMU + 1U + 1X)/17U, 17U/17X, 1U/(1X + 1U) and
      AFMU/(AFMU + 1U + 1X), respectively. Metabolites and internal standard were
      extracted with chloroform/isopropanol (85:15, v/v) and separated on a C18 column
      by an isocratic HPLC system using a two-step elution with manual switch from
      solvent A (0.1% acetic acid-methanol-acetonitrile, 92:4:5 v/v) to solvent B (0.1%
      acetic acid-methanol, 60:40, v/v), and detected at 280 nm. The method exhibited
      adequate metabolite separation (resolution factors >1.48), accuracy (94.1-106.3%)
      and intraday and interday precision <8.02 and <8.78%, respectively (n = 6).
      Smoking affected only CYP1A2, whereas gender had no effect in any enzyme
      activity. NAT-2 exhibited bimodal distribution, 63.6% of volunteers being slow
      acetylators. The developed RP-HPLC method was fully validated and successfully
      applied for the evaluation of CYP1A2, CYP2A6, XO and NAT-2 activities.

PMID- 17221923
TI  - Saturated amine oxides: Part 8. Hydroacridines: Part 27. Effects of N-oxidation
      and of N-quaternization on the 15N NMR chemical shifts of N-methylpiperidine
      derived mono-, bi-, and tricycloaliphatic tertiary amines.
AB  - The (15)N chemical shifts of 13 N-methylpiperidine-derived mono-, bi- and
      tricycloaliphatic tertiary amines, their methiodides and their N-epimeric pairs
      of N-oxides were measured, and the contributions of specific structural
      parameters to the chemical shifts were determined by multilinear regression
      analysis. Within the examined compounds, the effects of N-oxidation upon the
      (15)N chemical shifts of the amines vary from +56 ppm to +90 ppm (deshielding),
      of which approx. +67.7 ppm is due to the inductive effect of the incoming N(+)-
      O(-) oxygen atom, whereas the rest is due to the additive shift effects of the
      various C-alkyl substituents of the piperidine ring. The effects of
      quaternization vary from -3.1 ppm to +29.3 ppm, of which approx. +8.9 ppm is due
      to the inductive effect of the incoming N(+)--CH(3) methyl group, and the rest is
      due to the additive shift effects of the various C-alkyl substituents of the
      piperidine ring. The shift effects of the C-alkyl substituents in the amines, the
      N-oxides and the methiodides are discussed.

PMID- 17221924
TI  - NMR assignments of unusual flavonoids from the kino of Eucalyptus citriodora.
AB  - Two unusual flavonoids, 3,5,4',5''-tetrahydroxy-7-methoxy-6-[1-(p-hydroxy
      phenyl)ethyl]flavanone (1) and 3,5,7,4',5''-pentahydroxy-6-[1-(p-hydroxy
      phenyl)ethyl] flavanone (2), were isolated from the kino of Eucalyptus
      citriodora. Structural elucidation of the new compounds were established on the
      basis of spectral data, particularly by the use of 1D NMR and several 2D shift
      correlated NMR pulse sequences ((1)H, (1)H-COSY, HMQC, HMBC).

PMID- 17221925
TI  - Development and validation of an RP-HPLC-UV method for the determination of BOL
      303225-A, a new coumarin-based anti-inflammatory drug, in rat plasma.
AB  - A simple and rapid high-performance liquid chromatographic method was developed
      and validated for the analysis in rat plasma of BOL-303225-A, a new coumarin
      based anti-inflammatory drug. Liquid-liquid extraction was used for sample
      preparation. Chromatographic separation was achieved on a C(18) column using
      acetonitrile and water containing 1% triethylamine pH 3.5, adjusted with
      orthophosphoric acid (35.5:64.5 v/v) as mobile phase. The UV detector was set at
      324 nm. The method proved to be linear (r(2) > 0.99) and precise (RSD < 7%) over
      the concentration range 29-940 ng/mL, and was suitable for the support of
      pharmacokinetic studies in rats.

PMID- 17221926
TI  - Screening for pre-eclampsia and fetal growth restriction by uterine artery
      Doppler and PAPP-A at 11-14 weeks' gestation.
AB  - OBJECTIVE: To assess the role of maternal demographic characteristics, uterine
      artery Doppler velocimetry, maternal serum pregnancy-associated plasma protein-A
      (PAPP-A) and their combination in screening for pre-eclampsia and small-for
      gestational age (SGA) fetuses at 11-14 weeks. METHODS: This was a prospective
      study of 878 consecutive women presenting for a routine prenatal ultrasound
      examination at 11-14 weeks. Pulsed wave Doppler was then used to obtain uterine
      artery flow velocity waveforms and the mean pulsatility index (PI) of the uterine
      arteries was calculated. Maternal serum samples for PAPP-A were assayed. Along
      with maternal history, these measurements were compared in their ability to
      predict adverse outcome, defined as pre-eclampsia and/or SGA and/or placental
      abruption. RESULTS: Mean uterine artery PI > or = 95(th) centile and PAPP-A < or
      = 10(th) centile each predicted 23% of the women that developed pre-eclampsia and
      43% of cases of placental abruption. For SGA < or = 5(th) centile, mean uterine
      artery PI > or = 95(th) centile predicted 23% of cases and PAPP-A < or = 10(th)
      centile predicted 34%. Independent predictors for subsequent development of pre
      eclampsia were increased mean uterine artery PI > or = 95(th) centile (OR, 2.76;
      95% CI, 1.11-6.81) and maternal history of pre-eclampsia/hypertension (OR, 50.54;
      95% CI, 10.52-242.73). The predicting factors for SGA < or = 5(th) centile were
      increased mean uterine artery PI > or = 95(th) centile (OR, 2.0; 95% CI, 1.07
      3.74) and low PAPP-A (OR, 0.43; 95% CI, 0.20-0.93). Increased uterine artery PI
      was the only independent factor in the prediction of placental abruption (OR,
      8.49; 95% CI, 2.78-25.94). The combination of uterine artery PI and maternal
      history of pre-eclampsia/hypertension was better than was using uterine artery
      Doppler alone in predicting pre-eclampsia. Similarly, for the prediction of SGA <
      or = 5(th) centile, combining uterine artery Doppler and maternal serum PAPP-A
      was better than was uterine artery Doppler alone. In both cases, the difference
      approached statistical significance. CONCLUSIONS: The combination of maternal
      history with abnormal uterine artery Doppler and low PAPP-A level at 11-14 weeks
      achieves better results than does either test alone in the prediction of pre
      eclampsia and SGA.

PMID- 17221927
TI  - Automated mass correction and data interpretation for protein open-access liquid
      chromatography-mass spectrometry.
AB  - Characterization of recombinant protein purification fractions and final products
      by liquid chromatography-mass spectrometry (LC/MS) are requested more frequently
      each year. A protein open-access (OA) LC/MS system was developed in our
      laboratory to meet this demand. This paper compares the system that we originally
      implemented in our facilities in 2003 to the one now in use, and discusses, in
      more detail, recent enhancements that have improved its robustness, reliability,
      and data reporting capabilities. The system utilizes instruments equipped with
      reversed-phase chromatography and an orthogonal accelerated time-of-flight mass
      spectrometer fitted with an electrospray source. Sample analysis requests are
      accomplished using a simple form on a web-enabled laboratory information
      management system (LIMS). This distributed form is accessible from any intranet
      connected company desktop computer. Automated data acquisition and processing are
      performed using a combination of in-house (OA-Self Service, OA-Monitor, and OA
      Analysis Engine) and vendor-supplied programs (AutoLynx, and OpenLynx) located on
      acquisition computers and off-line processing workstations. Analysis results are
      then reported via the same web-based LIMS. Also presented are solutions to
      problems not addressed on commercially available, small-molecule OA-LC/MS
      systems. These include automated transforming of mass-to-charge (m/z) spectra to
      mass spectra and automated data interpretation that considers minor variants to
      the protein sequence-such as common post-translational modifications (PTMs).
      Currently, our protein OA-LC/MS platform runs on five LC/MS instruments located
      in three separate GlaxoSmithKline R&D sites in the US and UK. To date, more than
      8000 protein OA-LC/MS samples have been analyzed. With these user friendly and
      highly automated OA systems in place, mass spectrometry plays a key role in
      assessing the quality of recombinant proteins, either produced at our facilities
      or bought from external sources, without dedicating extensive amounts of analyst
      resource.

PMID- 17221928
TI  - A rapid method for quantitatively estimating metabolites in human plasma in the
      absence of synthetic standards using a combination of liquid chromatography/mass
      spectrometry and radiometric detection.
AB  - An approach to estimating the levels of drug-related metabolites in human plasma
      in the absence of synthesized chemical standards has been developed. High
      performance liquid chromatography/mass spectrometry (LC/MS) in combination with
      radiometric detection was used in this method. Biologically derived [(14)C]
      metabolites from preclinical in vitro and in vivo matrices are used as [(14)C]
      metabolite standards and their concentrations in matrices are calculated based on
      the corresponding radioactivity. The amount of drug-related metabolites in human
      plasma samples can be estimated by determining relative MS responses of
      metabolites between plasma and [(14)C] metabolite standards, and using the
      calculated concentrations of metabolite standards as calibrants. An example for
      the estimation of metabolites in human plasma was used to demonstrate the utility
      of this methodology.

PMID- 17221929
TI  - Oxygen-18 measurement of Andalusian olive oils by continuous flow
      pyrolysis/isotope ratio mass spectrometry.
AB  - We report a method for the determination of delta(18)O isotopic abundance in
      olive oils. The results obtained by applying the method to various Andalusian oil
      samples obtained in the 2004/05 and 2005/06 seasons are discussed in relation to
      olive variety, geographical origin, climate and ripeness index. Application of
      the method to samples of assured varietal purity exposed the influence of olive
      variety and origin but not of the ripeness index. The delta(18)O values for the
      2005/06 season are higher on average than those obtained in the colder 2004/05
      season. Results obtained for samples of the Picual and Hojiblanca varieties in
      Cordoba and Malaga in the 2005/06 season suggest a correlation between enrichment
      in heavy isotopes and latitude whereas no clear-cut effect of altitude was
      observed.

PMID- 17221931
TI  - Rapid protein identification using a disposable on-line clean-up/concentrating
      device and electrospray ionization mass spectrometry.
AB  - A simple, low-cost, expedient method has been developed for identification of
      proteins isolated from two-dimensional (2D) gels. The method described uses a
      disposable on-line clean-up device, a syringe infusion pump and electrospray
      ionization mass spectrometry (ESI-MS). The on-line clean-up and concentrating
      device is a tapered capillary column filled with 1.5 cm of 5 microm C18
      particles. The short column was easily prepared and was connected directly to the
      ESI source through a low-flow ESI sprayer. Peptides resulting from enzymatic
      digestion of proteins were eluted from the short column isocratically using a
      syringe infusion pump and analyzed by ESI-MS. This simple set-up was found useful
      in the analysis of proteins isolated from 2D gels. Compared to the more
      conventional micro-liquid chromatography/tandem mass spectrometry
      (microLC/MS/MS), this method can identify proteins rapidly without the need for
      an HPLC pump and removes the problem of cross-contamination caused by system
      carryover. These advantages make the method described competitive with
      conventional LC/MS even though the latter method gives slightly expanded sequence
      coverage.

PMID- 17221932
TI  - Determination of paclitaxel in human and rat blood samples after administration
      of low dose paclitaxel by HPLC-UV detection.
AB  - A simple and sensitive HPLC-UV method was developed for the determination of
      paclitaxel (TXL) in human and rat blood samples. 4-Hydroxybenzoic acid n-hexyl
      ester was used as an internal standard. TXL was extracted by a liquid-liquid
      extraction with tert-butylmethyl ether. The disturbing peaks in the case of serum
      sample were removed by pre-extraction with hexane. The separation of TXL was
      achieved within 25 min using an ODS column with 50% acetonitrile aqueous solution
      as a mobile phase at a flow rate of 1.0 mL/min. The eluent was monitored at 230
      nm, and the resulted retention times of TXL and IS were 11.2 and 20.4 min. The
      detection limits of TXL for human plasma, serum and rat plasma samples at a
      signal-to-noise ratio of 3 were 10, 9.5 and 7.5 ng/mL, respectively. The proposed
      methods were applicable to the determination of TXL in human patients' plasma
      ranging from 15 to 27 ng/mL. Furthermore, monitoring of the time course of TXL
      after its single administration to rat could be demonstrated.

PMID- 17221933
TI  - Determination of secnidazole in human plasma by high-performance liquid
      chromatography with UV detection and its application to the bioequivalence
      studies.
AB  - A simple, accurate, precise and sensitive HPLC-UV method was developed for the
      determination of secnidazole in human plasma. Secnidazole and tinidazole (IS)
      were extracted from 0.2 mL of human plasma by ethyl acetate. Secnidazole was then
      separated by HPLC on a Diamond C(18) column and quantified by ultraviolet
      detection at 319 nm. The mobile phase consisted of acetonitrile-aqueous 5 mm
      sodium acetate (30:70, v/v) containing of 0.1% acetic acid adjusted to pH 4.0,
      and the flow rate was 1.0 mL/min. The low limit of quantification was 0.1
      microg/mL. The method was linear over the concentration range 0.1-25.0 microg/mL
      (R(2) = 1.000). The recovery of secnidazole from human plasma ranged from 76.5 to
      89.1%. Inter- and intra-assay precision ranged from 3.3 to 10.7%. Secnidazole in
      plasma was stable when stored at ambient temperature for 8 h, at -20 degrees C
      for 2 weeks and at -20 degrees C for three freeze-thaw cycles. The developed
      method was successfully applied to the pharmacokinetic and bioequivalence studies
      between test and reference secnidazole tablets following a single 500 mg oral
      dosage to 20 healthy volunteers of both genders. Pharmacokinetics parameters
      T(max), C(max), AUC(0-)t, AUC(0-infinity), T(1/2) were determined of both
      preparations. The analysis of variance (ANOVA) did not show any significant
      difference between the two preparations and 90% confidence intervals fell within
      the acceptable range for bioequivalence. It was concluded that the two
      secnidazole preparations are bioequivalence and may be used interchangeably.

PMID- 17221934
TI  - Rapid quantification of lisinopril in human plasma by liquid
      chromatography/tandem mass spectrometry.
AB  - An assay based on protein precipitation and liquid chromatography/tandem mass
      spectrometry (LC-MS/MS) has been developed and validated for the quantitative
      analysis of lisinopril in human plasma. After the addition of enalaprilat as
      internal standard (IS), plasma samples were prepared by one-step protein
      precipitation using perchloric acid followed by an isocratic elution with 10 mm
      ammonium acetate buffer (pH adjusted to 5.0 with acetic acid)-methanol (70:30,
      v/v) on a Phenomenex Luna 5 mu C(18) (2) column. Detection was performed on a
      triple-quadrupole mass spectrometer utilizing an electrospray ionization (ESI)
      interface operating in positive ion and selected reaction monitoring (SRM) mode
      with the precursor to product ion transitions m/z 406 --> 246 for lisinopril and
      m/z 349 --> 206 for enalaprilat. Calibration curves of lisinopril in human plasma
      were linear (r = 0.9973-0.9998) over the concentration range 2-200 ng/mL with
      acceptable accuracy and precision. The limit of detection and lower limit of
      quantification in human plasma were 1 and 2 ng/mL, respectively. The validated LC
      MS/MS method has been successfully applied to a preliminary pharmacokinetic study
      of lisinopril in Chinese healthy male volunteers.

PMID- 17221935
TI  - Pharmacokinetic study of puerarin in rat serum by liquid chromatography tandem
      mass spectrometry.
AB  - A highly sensitive and specific atmospheric pressure chemical ionization liquid
      chromatography-tandem mass spectrometry method was developed for serum
      pharmacokinetic studies of puerarin in rats. Chromatography was carried out on a
      reversed-phase Phenomenex Synergi 4 microm Fusion-RP80 column (150 x 2.0 mm i.d.)
      using a mobile phase consisting of acetonitrile-water (10:90, v/v) in 10 mm
      NH(4)OAc with a flow rate of 0.2 mL/min. Puerarin was analyzed in the multiple
      reaction monitoring mode with a precursor/product ion transition of m/z 415/267.
      The method was demonstrated to be specific and sensitive, and a linear response
      was observed over a range of 2-5000 ng/mL in rat serum. The validated method was
      successfully applied to the characterization of the pharmacokinetics of puerarin
      in rat serum after oral administration to spontaneously hypertensive rats. The
      blood concentration-time profile of puerarin showed a rapid initial increase,
      reaching a maximum and then declining within 1 h. Puerarin could not be detected
      after 24 h. The main pharmacokinetic parameters for puerarin after oral
      administration were as follows: C(max) (3.54 +/- 2.03 mg/L), T(max) (0.68 +/-
      0.37 h), AUC(0-t) (7.29 +/- 3.79 mg h/L), AUC(0-infinity) (9.17 +/- 4.87 mg h/L),
      T(1/2) (1.7 +/- 0.6 h), CL/F (7.24 +/- 4.27 L/h/kg) and V/F (17.88 +/- 13.55
      L/h/kg).

PMID- 17221936
TI  - Determination of hydroxysafflor yellow A in rat plasma and tissues by high
      performance liquid chromatography after oral administration of safflower extract
      or safflor yellow.
AB  - A simple and reproducible HPLC method for quantification of hydroxysafflor yellow
      A (HSYA) in rat plasma and tissues after oral administration of safflower extract
      or safflor yellow (SY) was developed. Sample preparation was achieved by protein
      precipitation of plasma and tissue homogenates with three volumes of methanol. p
      Hydroxybenzaldehyde was used as the internal standard (IS). HSYA and IS were
      separated on a Hypersil BDS-C(18) column with a gradient elution system composed
      of acetonitrile and aqueous acetic acid. UV detection was used at 320 nm. The
      calibration curves were linear in all matrices (r(2) > 0.999) in the
      concentration ranges 0.51-101.36 microg/mL for plasma, 12.27-2454.46 microg/g for
      intestines and 0.96-192.20 microg/g for lung. The intra-day and inter-day
      precision were all less than 12.5%, and the extract recovery was in the range
      64.1-103.7% with RSD less than 15.6% for HSYA in all matrices. The method was
      used successfully to quantify HSYA in rat plasma and tissue samples to support a
      pharmacokinectic study.

PMID- 17221937
TI  - Quantitative characterization of hemodynamic properties and vasculature
      dysfunction of high-grade gliomas.
AB  - Aberrations in tumor and peritumoral vasculature may not be distinguishable by
      cerebral blood flow (CBF) or cerebral blood volume (CBV) alone. The relationships
      between CBF and CBV were examined to estimate vasculature-specific hemodynamic
      characteristics. Twenty glioma patients were studied with dynamic susceptibility
      T2*-weighted MRI [(dynamic contrast-enhanced magnetic resonance imaging (DSC
      MRI)] before and during week 1 and 3 of radiotherapy (RT). CBF and CBV were
      calculated from DSC-MRI, and relationships between the two were evaluated: the
      physiological measure of mean transit time (MTT) = CBV/CBF; empirical fitting
      using the power law CBV = constant x (CBF)(beta). Three different tissue types
      were assessed: the Gd-enhancing tumor volume (GEV); non-enhanced abnormal tissue
      located beyond GEV but within the abnormal hyperintense region on FLAIR images
      (NEV); normal tissue in the hemisphere contralateral to the tumor (CNT). The
      effects of tissue types, CBV magnitudes (low, medium and high), before and during
      RT, on MTT and beta were analyzed by analysis of variance (ANOVA). The MTT and
      beta for the three tissue types were significantly different (p < 0.009). MTT
      increased from CNT (1.60 s) to NEV (1.93 s) to GEV (2.28 s) (p < 0.0005). beta
      was significantly greater in GEV (1.079) and NEV (1.070) than in CNT (1.025).
      Beta increased with increasing CBV magnitude while MTT was independent of CBV
      magnitude. There was a significant decrease in MTT of NEV and GEV during week 3
      of RT compared with pre-RT values for all CBV magnitudes. There was a significant
      increase in beta during RT in the tumor and peritumor. Progressive abnormalities
      in vasculature and hemodynamic characteristics of the vascular bed were
      delineated, with significant disorder in the tumor but mild abnormality in
      peritumoral tissue.

PMID- 17221938
TI  - Atractylenolide I and atractylenolide III inhibit Lipopolysaccharide-induced TNF
      alpha and NO production in macrophages.
AB  - In order to clarify the mechanism involved in the antiinflammatory activity of
      atractylenolide I and atractylenolide III from the rhizomes of Atractylodes
      macrocephala Koidz, their effects on tumor necrosis factor-alpha (TNF-alpha) and
      nitric oxide (NO) production in peritoneal macrophages were examined.
      Atractylenolide I and atractylenolide III decreased the TNF-alpha level in LPS
      stimulated peritoneal macrophages in a dose-dependent manner, their IC(50) values
      were 23.1 microm and 56.3 microm, respectively. RT-PCR analysis indicated that
      they inhibited TNF-alpha mRNA expression. Furthermore, they inhibited NO
      production in LPS-activated peritoneal macrophages, the IC(50) value of
      atractylenolide I was 41.0 microm, and the inhibition ratio of 100 microm of
      atractylenolide III was 45.1% +/- 6.2%. The activity analysis of inducible nitric
      oxide synthase (iNOS) indicated that they could inhibit the activity of iNOS,
      their IC(50) values were 67.3 microm and 76.1 microm, respectively. Western blot
      analysis showed that atractylenolide I and atractylenolide III attenuated LPS
      induced synthesis of iNOS protein in the macrophages, in parallel. These results
      imply that the antiinflammatory mechanism of atractylenolide I and
      atractylenolide III may be explained at least in part, by the inhibition of TNF
      alpha and NO production. Atractylenolide I showed more potent inhibition than
      atractylenolide III in the production of TNF-alpha and NO in LPS-activated
      peritoneal macrophages. So, atractylenolide I could be a candidate for the
      development of new drugs to treat inflammatory diseases accompanied by the
      overproduction of TNF-alpha and NO.

PMID- 17221939
TI  - Screening of some medicinal plants from cameroon for beta-lactamase inhibitory
      activity.
AB  - In efforts to find new bioactive beta-lactamase inhibitors, this study
      investigated 16 Cameroonian plants belonging to 10 families which were evaluated
      for anti-beta-lactamase activity. The investigation showed that extracts 2, 6, 3
      and 5 of the 16 plants investigated presented interesting in vitro beta-lactamase
      inhibition (over 90%), respectively, of the beta-lactamases TEM-1, OXA-10, IMP-1
      and P99. These extracts were from Mammea africana (all beta-lactamases), Garcinia
      lucida, G. kola (OXA-10, IMP-1 and P99), Bridelia micrantha (OXA-10, P99), Ochna
      afzelii (OXA-10, P99), Prunus africana (IMP-1) and Adenia lobata (TEM-1). After
      elimination of tannins (according to the European Pharmacopoeia) the extracts
      from B. micrantha, G. lucida and M. africana were tested further for their anti
      beta-lactamase activity. The extracts from B. micrantha and G. lucida exhibited
      potent inhibitory activity, respectively, of beta-lactamase OXA-10 (IC(50) = 0.02
      mg/mL) and P99 (IC(50) = 0.01 mg/mL). The anti-beta-lactamase activity of M.
      africana extract was weak. The isolation and the structural elucidation of the
      active constituents of G. lucida and B. micrantha will provide useful leads in
      the development of beta-lactamase inhibitors.

PMID- 17221940
TI  - Issues in applied statistics for public health bioterrorism surveillance using
      multiple data streams: research needs.
AB  - The objective of this report is to provide a basis to inform decisions about
      priorities for developing statistical research initiatives in the field of public
      health surveillance for emerging threats. Rapid information system advances have
      created a vast opportunity of secondary data sources for information to enhance
      the situational and health status awareness of populations. While the field of
      medical informatics and initiatives to standardize healthcare-seeking encounter
      records continue accelerating, it is necessary to adapt analytic and statistical
      methodologies to mature in sync with sibling information science technologies.
      One major right-of-passage for statistical inference is to advance the optimal
      application of analytic methodologies for using multiple data streams in
      detecting and characterizing public health population events of importance. This
      report first describes the problem in general and the data context, then
      delineates more specifically the practical nature of the problem and the related
      issues. Approaches currently applied to data with time-series, statistical
      process control and traditional inference concepts are described with examples in
      the section on Statistics and the Role of the Analytic Surveillance Data Monitor.
      These are the techniques that are providing substance to surveillance
      professionals and enabling use of multiple data streams. The next section
      describes use of a more complex approach that takes temporal as well as spatial
      dimensions into consideration for detection and situational awareness regarding
      event distributions. The space-time statistic has successfully been used to
      detect and track public health events of interest. Important research questions
      which are summarized at the end of this report are described in more detail with
      respect to the methodological application in the respective sections. This was
      thought to help elucidate the research requirements as summarized later in the
      report. Following the description of the space-time scan statistical application;
      this report extends to a less traditional area of promise given what has been
      observed in recent application of analytic methods. Bayesian networks (BNs)
      represent a conceptual step with advantages of flexibility for the public health
      surveillance community. Progression from traditional to the more extending
      statistical concepts in the context of the dynamic status quo of responsibility
      and challenge, leads to a conclusion consisting of categorical research needs.
      The report is structured by design to inform judgment about how to build on
      practical systems to achieve better analytic outcomes for public health
      surveillance. There are references to research issues throughout the sections
      with a summarization at the end, which also includes items previously unmentioned
      in the report.

PMID- 17221941
TI  - Determination of antioxidant and radical scavenging activity of Basil (Ocimum
      basilicum L. Family Lamiaceae) assayed by different methodologies.
AB  - The antioxidant properties of plants have been investigated, in the light of
      recent scientific developments, throughout the world due to their potent
      pharmacological activities and food viability. Basil (Ocimum basilicum L. Family
      Lamiaceae) is used as a kitchen herb and as an ornamental plant in house gardens.
      In the present study, the possible radical scavenging and antioxidant activity of
      the water (WEB) and ethanol extracts (EEB) of basil was investigated using
      different antioxidant methodologies: 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free
      radical scavenging, scavenging of superoxide anion radical-generated non
      enzymatic system, ferric thiocyanate method, reducing power, hydrogen peroxide
      scavenging and metal chelating activities. Experiments revealed that WEB and EEB
      have an antioxidant effects which are concentration-dependent. The total
      antioxidant activity was performed according to the ferric thiocyanate method. At
      the 50 microg/mL concentration, the inhibition effects of WEB and EEB on
      peroxidation of linoleic acid emulsion were found to be 94.8% and 97.5%,
      respectively. On the other hand, the percentage inhibition of a 50 microg/mL
      concentration of BHA, BHT and alpha-tocopherol was found to be 97.1%, 98.5% and
      70.4% inhibition of peroxidation of linoleic acid emulsion, respectively. In
      addition, WEB and EEB had effective DPPH radical scavenging, superoxide anion
      radical scavenging, hydrogen peroxide scavenging, reducing power and metal
      chelating activities. Additionally, these various antioxidant activities were
      compared with BHA, BHT and alpha-tocopherol as reference antioxidants. The
      additional total phenolic content of these basil extracts was determined as the
      gallic acid equivalent and were found to be equivalent.

PMID- 17221942
TI  - Treatment decision difficulties and post-operative distress predict persistence
      of psychological morbidity in Chinese women following breast cancer surgery.
AB  - BACKGROUND: The patterns and determinants of longer-term psychological morbidity
      in women following breast cancer surgery have not been described for Chinese
      populations. METHODS: Chinese women were assessed at 3-days, 4-months and 8
      months following breast surgery, on treatment decision-making difficulty (TDMD),
      satisfaction with treatment outcome (E-OI), self efficacy (GSeS), optimism (C-LOT
      R), consultation satisfaction (C-MISS-R), physical symptom distress (PSD) and
      psychological morbidity (CHQ-12) and compared using polynomial logistic models.
      RESULTS: Of 303/405 women providing complete data, 33% received chemotherapy and
      26% radiotherapy. GSeS, CLOTR and TDMD scores were moderate. Though the
      proportion of women meeting psychological morbidity case-criteria declined from
      78% (95% Confidence Interval 73-83%) at Baseline to 64% (59-69%) at 8-months,
      almost 50% (44-54%) of women remained distressed over the 8-month period. After
      adjustment for demographic and clinical factors, severity of psychological
      morbidity at 4-months was predicted by PSD, disappointment and higher Baseline
      CHQ12, and among moderate/severe cases only, greater TDMD and pessimistic
      outlook. At 8-months, CHQ12 scores were predicted by PSD, Baseline CHQ-12, and
      difficulties with TDM. CONCLUSION: TDM difficulties, early post-surgical
      psychological and physical symptom distress indicate risk for prolonged distress
      in Chinese women following breast cancer surgery.

PMID- 17221943
TI  - Making patient-level estimates from medical encounter records using a
      multiplicity estimator.
AB  - The National Ambulatory Medical Care Survey (NAMCS) is a nationally
      representative survey of medical encounters in physician offices in the United
      States. Data from this survey and its counterpart in hospitals, the National
      Hospital Ambulatory Medical Care Survey (NHAMCS), have been used to investigate
      physician treatment and prescribing patterns. A limitation of these data,
      however, is that they represent visits rather than patients. Starting in 2001,
      the survey questionnaires began collecting information on the number of past
      visits the patient had to the sample provider during the one-year period prior to
      the sampled visit. This information was used to estimate number of patients from
      the NAMCS and NHAMCS visit data using a multiplicity estimator. The resulting
      distribution of patients by the number of annual visits is similar to the
      distribution of persons in the U.S. making ambulatory care visits from a
      population-based survey. This estimation technique may be useful in estimating
      patients with clinical characteristics that are difficult to collect from a
      population-based survey. Published in 2007 by John Wiley & Sons, Ltd.

PMID- 17221944
TI  - OEIS complex: prenatal ultrasound and autopsy findings.
AB  - OBJECTIVE: To describe prenatal ultrasound and autopsy findings in fetuses with
      OEIS (omphalocele, bladder exstrophy, imperforate anus, spina bifida) complex.
      METHODS: This was a retrospective study of the nine cases with OEIS complex
      diagnosed at our center using detailed fetal ultrasound during the last 10 years.
      We summarized the fetal ultrasound findings that led to the diagnosis and
      compared them with the autopsy results. RESULTS: All affected fetuses were
      diagnosed using detailed fetal ultrasound after 16 weeks' gestation. The main
      prenatal findings were omphalocele, skin-covered lumbosacral neural tube defect,
      non-visualized bladder and limb defects. Prenatal sonography failed to detect the
      abnormal genitalia, bladder exstrophy and anal atresia. All cases had
      abnormalities in a 'diaper distribution', which helped in making the prenatal
      diagnosis. Eight of the nine couples chose to terminate the pregnancies following
      multidisciplinary counseling. The pregnancy that was continued was a case with
      dizygotic twins discordant for OEIS, and the affected fetus died in utero.
      CONCLUSIONS: The combination of the following ultrasound findings: ventral wall
      defect, spinal defect and a non-visualized bladder with or without limb defects,
      are characteristic of OEIS complex. Diagnosis can be made with confidence as
      early as 16 weeks' gestation, although earlier diagnosis may be possible.

PMID- 17221945
TI  - Tetrahedral boron chemistry for the preparation of highly efficient "cascatelle"
      devices.
AB  - The replacement of the two fluorine atoms on the boron center of the well-known
      Bodipy fluorophore by functionalized acetylenic groups opens the way to a new
      family of highly luminescent, redox active, and stable fluorophores termed "E
      Bodipy" species. The substitution is effective for ethynyl-lithium reagents
      incorporating tolyl, naphthyl, pyrenyl, fluorenyl, and terpyridinyl units. The
      protocol also tolerates the presence of various functional groups in the
      dipyrromethene meso position such as pyrene, phenylethynylpyrene, 4'-terpyridine,
      and iodophenyl. The last of these is particularly useful for a further coupling
      reaction enabling introduction of a flexible arm bearing a succinimidyl unit
      reactive toward primary amines. X-ray structure determinations of two E-Bodipy
      compounds confirm the introduction of the ethynyl units and show the boron atoms
      to have a distorted tetrahedral environment, with B-C(ethynyl) approximately 1.59
      A and both boron atoms lying essentially in the mean planes of the dipyrromethene
      units. All the new compounds show intense electronic absorption bands (epsilon
      60,000-70,000 M-1 cm-1), high quantum yields (>80%), and slow rates of
      nonradiative decay. Absorption by the aromatic substituents results in a
      "cascatelle" process leading to emission exclusively through the
      boradiazaindacene entity and thus large virtual Stokes' shift (>10,000 cm-1). The
      new compounds are also redox active, with the formation of both Bodipy+* and
      Bodipy-* occurring more readily than for F-Bodipy species. The molecules in their
      excited states are strong reducing agents.

PMID- 17221946
TI  - Piperazimycins: cytotoxic hexadepsipeptides from a marine-derived bacterium of
      the genus Streptomyces.
AB  - Three potent cancer cell cytotoxins, piperazimycins A-C (1-3), have been isolated
      from the fermentation broth of a Streptomyces sp., cultivated from marine
      sediments near the island of Guam. The structures of these cyclic
      hexadepsipeptides were assigned by a combination of spectral, chemical, and
      crystallographic methods. The piperazimycins are composed of rare amino acids,
      including hydroxyacetic acid, alpha-methylserine, gamma-hydroxypiperazic acid,
      and gamma-chloropiperazic acid. The novel amino acid residues 2-amino-8-methyl
      4,6-nonadienoic acid and 2-amino-8-methyl-4,6-decadienoic acid were found as
      components of piperazimycins A and C, respectively. When screened in the National
      Cancer Institute's 60 cancer cell line panel, piperazimycin A exhibited potent in
      vitro cytotoxicity toward multiple tumor cell lines with a mean GI50 of 100 nM.

PMID- 17221947
TI  - Density functional theory investigations on sulfur ylide promoted
      cyclopropanation reactions: insights on mechanism and diastereoselection issues.
AB  - The mechanism and diastereoselectivity of synthetically useful sulfur ylide
      promoted cyclopropanation reactions have been studied using the density
      functional theory method. Addition of different substituted ylides (Me2S+CH-R) to
      enone ((E)-pent-3-en-2-one, MeHC=CH-COMe) has been investigated. The nature of
      the substituent on the ylidic carbon brings about subtle changes in the reaction
      profile. The stabilized (R=COMe) and semistabilized (R=Ph) ylides follow a cisoid
      addition mode, leading to 1,2-trans and 1,2-cis cyclopropanes, respectively, via
      syn and anti betaine intermediates. The simplest and highly reactive model ylide
      (R=H) prefers a transoid addition mode. Diastereoselectivity is controlled by the
      barrier for cisoid-transoid rotation in the case of stabilized ylides, whereas
      the initial electrophilic addition is found to be the diastereoselectivity
      determining step for semistabilized ylides. High selectivity toward trans
      cyclopropanes with stabilized ylides are predicted on the basis of the relative
      activation energies of diastereomeric torsional transition states. The energy
      differences between these transition states could be rationalized with the help
      of weak intramolecular as well as other stereoelectronic interactions.

PMID- 17221948
TI  - Spin system assignment of homo-o-phenylene ethynylene oligomers.
AB  - We previously reported the synthesis and solution characterization of short o
      phenylene ethynylene (oPE) foldamers. Proton correlation techniques are not
      adequate for NMR assignment in these compounds as the ethynylene linkers
      interrupt proton connectivity. In order to facilitate structural characterization
      and more fully harness the power of NMR, it is necessary to know the sequence of
      spin systems along the molecular backbone. For example, spin system assignment is
      required to unambiguously assign NOE correlations for structural determination of
      folded forms in solution. Therefore, we developed a method to assign the aromatic
      spin systems in these compounds using HMBC experiments. This has been performed
      for tetrameric (Es4), pentameric (Es5), and hexameric (Es6) oligomers and is
      expected to prove useful for this class of foldamers in general. The proton
      assignments obtained by this technique have been useful toward confirming the
      previous hypotheses of helical folding in oPE systems.

PMID- 17221949
TI  - Spin-polarized conceptual density functional theory study of the regioselectivity
      in ring closures of radicals.
AB  - The regioselectivity of ring-forming radical reactions is investigated within the
      framework of the so-called spin-polarized conceptual density functional theory.
      Two different types of cyclizations were studied. First, a series of model
      reactions of alkyl- and acyl-substituted radicals were investigated. Next,
      attention was focused on the radical cascade cyclizations of N-alkenyl-2
      aziridinylmethyl radicals (a three-step mechanism). In both of these reactions,
      the approaching radical (carbon or nitrogen centered) adds to a carbon-carbon
      double bond within the same molecule to form a radical ring compound. In this
      process, the number of electrons is changing from a local point of view (a charge
      transfer occurs from one part of the molecule to another one) at constant global
      spin number Ns (both the reactant and the product ring compound are in the
      doublet state). It is shown that the experimentally observed regioselectivities
      for these ring-closure steps can be predicted using the spin-polarized Fukui
      functions for radical attack, f0NN(r).

PMID- 17221950
TI  - Theoretical study on the mechanism of the [2+1] thermal cycloaddition between
      alkenes and stable singlet (phosphino)(silyl)carbenes.
AB  - The mechanism and the origins of the stereocontrol observed in the reaction
      between differently substituted alkenes and stable (phosphino)(silyl)carbenes
      giving cyclopropanes have been studied computationally. These cyclopropanation
      reactions proceed via asynchronous concerted mechanisms involving early
      transition structures with a significant charge transfer from the carbene to the
      alkene moiety. The geometric features of these transition structures preclude a
      significant overlap between the orbitals required for secondary orbital
      interactions between the reactants. The stereoselectivity observed experimentally
      stems from favorable electrostatic and steric interactions between the reactants
      leading to the stereoisomers in which the phosphanyl and carbonyl or aryl groups
      are cis to each other.

PMID- 17221951
TI  - Rearrangement of 1,3-dipolar cycloadducts derived from bis(phenylazo)stilbene: a
      DFT level mechanistic investigation.
AB  - The 1,3-dipolar cycloaddition of bis(phenylazo)stilbene with activated ethene and
      ethyne derivatives and the subsequent rearrangement of the cycloadducts have been
      studied using model compounds at the B3LYP/6-31G(d) level of density functional
      theory (DFT). From the structural and electronic features, a five-membered
      zwitterionic ring system 9 (1,2,3-triazolium-1-imide system) formed from
      bis(phenylazo)ethylene is confirmed as the active 1,3-dipole species in the
      reaction. Formation of the 1,3-dipolar cycloadduct from the alkyne derivative is
      found to be 26.0 kcal/mol exergonic, and it requires an activation free energy of
      19.4 kcal/mol. The 1,3-cycloadduct formed in the reaction undergoes a very facile
      migration of a nitrogen-bearing fragment, passing through a zwitterionic
      transition state. A small activation free energy of 8.2 kcal/mol is observed for
      this step of the reaction, and it is 19.6 kcal/mol exergonic. Further activation
      of the newly formed rearranged product is possible under elevated temperatures,
      again passing through a zwitterionic transition state and resulting in the
      formation of 2,5-dihydro-1,2,3-triazine derivatives. Such derivatives have been
      recently reported by Butler et al. (J. Org. Chem. 2006, 71, 5679). The charge
      separation in 9 and the zwitterionic transition states are stabilized through the
      pi-system of the phenyl rings and the carbonyl groups. Similar structural,
      electronic, and mechanistic features are obtained for the reaction of 9 with the
      ethylenic dipolarophile acrylonitrile. Molecular electrostatic potential analyses
      of the 1,3-dipole and the zwitterionic transitions states are found to be very
      useful for characterizing their electron delocalization features. The solvation
      effects can enhance the feasibility of these reactions as they stabilize the
      zwitterionic transition states to a great extent.

PMID- 17221952
TI  - Tripodal, cooperative, and allosteric transphosphorylation metallocatalysts.
AB  - Three artificial amino acids derived from l-serine by replacing the hydroxyl
      moiety with 1,4,7-triazacyclononane, 1,5,9-triazacyclododecane, and 1,4,7,10
      tetraazacyclododecane, respectively, have been connected to the three arms of the
      tetraamine tris(2-aminoethyl)amine, Tren, to obtain tripodal ligands. They are
      able to bind up to four metal ions (like CuII and ZnII), three with the
      polyazamacrocycles and one with the Tren platform. Some of the ZnII complexes of
      these tripodal ligands proved to be good catalysts for the cleavage of the RNA
      model substrate 2-hydroxypropyl-p-nitrophenylphosphate (HPNP). Studies of the
      catalytic activity in the presence of increasing amounts of ZnII show that the
      complexes represent minimalist examples of metallocatalysts with cooperativity
      between the metal centers and allosteric control by a metal ion. The Tren binding
      site constitutes the allosteric regulation unit, while the three ZnII-azacrown
      complexes provide the cooperative, catalytic site. The allosteric role of the
      ZnII ion located in the Tren binding site was unambiguously demonstrated by
      studying the catalytic activity of a derivative unable to complex ZnII in that
      site. In this case, the cooperativity between the three ZnII ions bound to the
      peripheral azacrowns was totally suppressed. The kinetic analysis has shown that
      cooperativity is due to neither the occurrence of general-acid/general-base
      catalysis nor a decreased binding of the substrate because of the deprotonation
      of a water molecule bound to the complex but, rather, stabilization of the
      complexed substrate in its transformation into the transition state.

PMID- 17221953
TI  - Studies toward the asymmetric synthesis of the right part of the mycalamides.
AB  - Described herein is the asymmetric synthesis of a functionalized, trioxadecalin
      unit that comprises the right-hand part of the mycalamides and related natural
      products. The synthetic route involves a 16-step sequence that accomplishes the
      formation of two heterocyclic rings and the generation of five stereocenters. The
      synthesis commenced with a C2-symmetric starting material, diethyl D-tartrate,
      and took advantage of a relay of diastereoselective reactions to extend this four
      carbon chain and introduce new chiral centers. Subsequent electrophile-mediated
      cyclization afforded the desired pyran ring, which was then transformed into the
      desired, functionalized trioxadecalin skeleton.

PMID- 17221954
TI  - Diastereocontrolled synthesis of enantioenriched 3,4-disubstituted beta-prolines.
AB  - Enantioenriched 3,4-disubstituted beta-prolines have been prepared with a high
      diastereocontrol through a carbometalation reaction or through a domino Michael
      addition/carbometalation reaction.

PMID- 17221955
TI  - Novel syntheses of chiral beta- and gamma-amino acid derivatives utilizing N
      protected (aminoacyl)benzotriazoles from aspartic and glutamic acids.
AB  - Friedel-Crafts reactions of N-protected (alpha-aminoacyl)benzotriazoles with
      hetero- and benzenoid- aromatics give alpha-amino ketones that can be reduced by
      either triethyl silane or sodium borohydride to form the corresponding beta- and
      gamma-amino acid derivatives. The preservation of chirality throughout this
      process is confirmed by chiral HPLC results.

PMID- 17221956
TI  - Highly selective double chalcogenation of isocyanides with disulfide-diselenide
      mixed systems.
AB  - A highly selective method for introducing thio and seleno groups into a variety
      of isocyanides has been developed based on the elucidation of the relative
      reactivities of organic dichalcogenides and chalcogen-centered free radicals.
      When the reactions of aromatic isocyanides (ArNC) with organic disulfides
      (R'SSR') and diselenides (R''SeSeR'') are conducted upon irradiation with a
      tungsten lamp through Pyrex (hnu>300 nm), simultaneous introduction of both thio
      and seleno groups into the isocyanides takes place to provide the corresponding
      thioselenation products (R'S-C(=NAr)-SeR'') in good yields with excellent
      selectivity. In the cases of aliphatic isocyanides (RCN), a novel diselenide
      assisted bisthiolation of RNC with diaryl disulfides (Ar'SSAr') proceeds
      successfully to give the corresponding bisthiolation products (Ar'S-C(=NR)-SAr'),
      although the same photoirradiated reaction of RNC with diaryl disulfides does not
      occur in the absence of diselenide. These double chalcogenation reactions are
      assumed to proceed via the formation of imidoyl radical intermediates by the
      reaction of isocyanides with relatively reactive thio radicals (compared with
      seleno radicals). The obtained thioselenation products can be employed as useful
      precursors for the construction of beta-lactam framework by the formal [2+2]
      cyclization with ketene equivalents.

PMID- 17221957
TI  - Double-stranded cycles: toward C84's belt region.
AB  - The reactivity of the double-stranded hydrocarbon cycle with two ether bridges
      (1) toward iodotrimethylsilane (TMSI) was investigated in some detail. The carbon
      skeleton of cycle 1 resembles the belt region of a C84 fullerene which makes it a
      potential precursor to the long sought after fully aromatic derivative. Upon
      exposure to TMSI, cycle 1 undergoes a cascade of reactions which involve
      different states of iodination/reduction which ultimately lead to the
      hydrogenated cycle 5a, whose structure was proven by single-crystal X-ray
      analysis. A deeper insight into mechanistic aspects of this sequence of
      conversions was gained by performing the reaction under dry and wet conditions,
      whereby the latter involved both normal and deuterated water. With the help of
      detailed NMR correlation studies and DFT computations, all important aspects were
      clarified including an unexpected selective H/D exchange at the naphthalenic
      moieties.

PMID- 17221959
TI  - Two-directional elaboration of hydroxyacetone under thermodynamically controlled
      conditions: allylation or 2-propynylation and aldol reaction.
AB  - Enolate generated from O-(tetrahydropyran-2-yl)hydroxyacetone under
      thermodynamically controlled conditions (1.3 equiv of NaH, THF, 0 degrees C to
      rt) was allylated at the carbon bearing the protected hydroxy group with very
      high regioselectively. When tert-BuOH, equivalent to the excessive portion of
      initially added NaH, was introduced into the mixture followed by addition of
      aldehyde, aldol reaction took place on the methyl group to give 1-substituted 4
      hydroxy-(1E),6-heptadien-3-one in acceptable yields after acidic treatment of the
      mixture for dehydration and deprotection. Introducing a chiral auxiliary
      protecting group into hydroxyacetone led to asymmetric allylation though
      stereoselectivity was around 50% ee. Thus, the hidden aspect of the
      chemoselective nature of protected hydroxyacetone-derived enolate generated under
      thermodynamically controlled conditions has opened a new avenue for two
      directional elaboration of hydroxyacetone that should be potentially useful in
      organic synthesis.

PMID- 17221960
TI  - Synthesis and structure of alkyl-substituted fused thiophenes containing up to
      seven rings.
AB  - We have established a series of synthetic methods to synthesize alkyl-substituted
      fused thiophenes with degrees of fusion from two to seven rings. These fused
      thiophene ring compounds have very good solubility in common organic solvents,
      making possible the solution processing of these compounds for electronic
      applications. The UV absorption of these fused thiophenes is blue-shifted when
      compared with their hydrocarbon counterparts. The larger band gaps result in much
      better stability. Single-crystal X-ray results for 3,6-didecanyldithieno[2,3
      d:2',3'-d']thieno[3,2-b:4,5-b'']dithiophene (FT5) and 3,7-didecanylthieno[3,2
      b]thieno[2',3':4,5]thieno[2,3-d]thiophene (FT4) demonstrate that both compounds
      form pi-stacking structures instead of a herringbone-type of packing motif. This
      more favorable pi-stacked structure may lead to better material electronic
      properties such as mobility in devices fabricated with these compounds.

PMID- 17221958
TI  - Single enantiomer epoxides by bromomandelation of prochiral alkenes.
AB  - A combination of mandelic acid and N-bromosuccinimide efficiently converts
      prochiral alkenes into a readily separable 1:1 mixture of the bromomandelates.
      The diastereomerically pure bromomandelates are then converted into a variety of
      enantiomerically pure products. Terminal alkenes are converted into
      enantiomerically pure epoxides. Cyclohexene is converted into enantiomerically
      pure cis-2-azidocyclohexanol and cis-2-phenylthiocyclohexanol.

PMID- 17221961
TI  - Templating photodimerization of trans-cinnamic acid esters with a water-soluble
      Pd nanocage.
AB  - A water-soluble octahedral Pd nanocage acting as a reaction vessel templates the
      photodimerization of substituted trans-cinnamic acid methyl esters in water.
      Irradiation of the host-guest complexes of trans-cinnamic acid methyl esters with
      the Pd nanocage resulted in selective formation of a syn head-head dimer in
      addition to the corresponding cis isomer. These results suggest that the guest
      molecules are preoriented in a selective fashion with the hydrophilic ester group
      facing water and the hydrophobic aryl group tucked within the cavity of the host.
      Such an orientation occurs at the hydrophobic-hydrophilic interface between the
      nanocage exterior and interior. Weak intermolecular C-H-pi and pi-pi interactions
      between the host and the guest(s) are likely to be responsible for the lack of
      mobility of the reactant olefins during their short excited-state lifetime.

PMID- 17221962
TI  - Preparation and properties of rotaxanes formed by dimethyl-beta-cyclodextrin and
      oligo(thiophene)s with beta-cyclodextrin stoppers.
AB  - Novel cyclodextrin rotaxanes with oligothiophene as an axis molecule have been
      prepared by the Suzuki coupling reaction of 6-O-(4-iodophenyl)-beta-CD (6-I-Ph
      beta-CD) with di(1,3,2-dioxaborolan-2-yl)-oligothiophene (oligothiophene diboric
      ethylene glycol esters) in aqueous solutions of dimethyl-beta-cyclodextrin (DM
      beta-CD). These reactions gave [2]rotaxanes and [3]rotaxanes, which were isolated
      by reversed phase chromatography. The fluorescence intensities of rotaxanes are
      higher than those of dumbbell-shaped molecules (without DM-beta-CD) in aqueous
      solutions. The inclusion ratio and chain length of rotaxanes have been found to
      relate to the emission properties and emission intensities of oligothiophene. In
      aqueous solutions, fluorescence quantum yields of rotaxanes are higher than those
      of dumbbell-shaped molecules. The increase in the fluorescence efficiency of
      rotaxane is caused by suppression of intermolecular interactions, indicating the
      effect of insulated oligothiophene with DM-beta-CD. beta-CD at the both ends of
      rotaxanes functions not only as bulky stoppers but also as the recognition site
      for guest molecules, as verified by fluorescence quenching experiments.

PMID- 17221963
TI  - Janus-AT bases: synthesis, self-assembly, and solid state structures.
AB  - The high yielding synthesis of heterocycles with defined H-bond accepting and
      donating capabilities provides for the design of self-assembling structures and
      specific recognition of biological targets. Herein we report the syntheses and
      solid-state structures of three self-complementary uracil/thymine derivatives
      where each presents the standard ADA face inherently complementary to adenine and
      a synthetically appended DAD face complementary to uracil/thymine. These
      heterocycles, which have never before been reported or characterized, represent
      diaminopurine-uracil/thymine hybrids that, in two of the three cases, relate to
      previously reported heterocyclic hybrids of G and C. All three heterocycles
      crystallized to afford the first X-ray crystal structures of self-complementary
      heterocycles capable of ADA-DAD pairing. The potential use in DNA and RNA
      recognition are briefly discussed.

PMID- 17221964
TI  - Oxidative and reductive carbodiazenylation of nonactivated olefins.
AB  - Procedures for the carbodiazenylation of nonactivated olefins with a wide range
      of aryldiazonium salts have been developed. The azo compounds obtained can serve
      as valuable precursors for beta-arylamines (carboamination products), beta-amino
      acids, ketones, and various heterocyclic structures.

PMID- 17221965
TI  - 1-(2,4,6-triisopropylphenyl)ethylamine: a new chiral auxiliary for the asymmetric
      synthesis of gamma-amino acid derivatives.
AB  - The title compound has proven to be an excellent chiral auxiliary for nitrones in
      SmI2-mediated reductive coupling with alpha,beta-unsaturated esters. A variety of
      such nitrones, prepared from aldehydes and enantiopure N-hydroxy-1-(2,4,6
      triisopropylphenyl)ethylamine, afforded gamma-N-hydroxyamino esters in high
      yields and diastereomeric purity. These adducts, readily available as either
      enantiomer, could be transformed into gamma-N-acetoxyamino esters, N-Boc-gamma
      amino esters, and gamma-lactams.

PMID- 17221966
TI  - Studies of the electron-promoted cope cyclization of 2,5-phenyl-substituted 1,5
      hexadiene radical anions.
AB  - This work describes studies of the electron-promoted Cope cyclization of 2,5
      phenyl-1,5-hexadiene radical anions in a flowing afterglow triple quadrupole mass
      spectrometer. The electronic properties of the hexadienes have been
      systematically modified by using aromatic substituents at the 2- and 5-positions
      of the hexedienes, including those with nitro, trifluoromethyl, fluoro, chloro,
      and acetyl groups. Ions were formed by the thermal attachment of electrons in the
      gas phase. Structures of the molecular radical anions were probed to determine
      whether they undergo cyclization to a cyclohexane-1,4-diyl anion structure by
      examining chemical reactivity with neutral reagents including carbon dioxide,
      carbon disulfide, and nitric oxide. First-order rate constants for the reactions
      of ions were measured, and the reaction efficiencies were determined. Based on
      the reactivity results, a thermochemical model has been developed, which predicts
      the reaction thermochemistry by using thermochemical properties of model systems.
      The observed reactivity from ion-molecule reactions and the study of reaction
      rates show that the ion of 2,5-dicyanohexadiene and 2,5-di(4,4'-trifluoromethyl
      phenyl)-1,5-hexadiene undergo Cope cyclization, whereas the radical anions having
      substituents such as the fluoro, nitro, chloro, and acetyl groups do not.

PMID- 17221967
TI  - Reactivity of indanedioneketene dimer with amines.
AB  - The highly reactive indanedioneketene 5, resulting from the thermal decomposition
      of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone (lawsone, 4), in the
      absence of nucleophiles dimerizes to the corresponding tetraoxo spiro oxetanone 6
      in quantitative yield. This oxetanone exhibits an interesting reactivity toward
      amines.

PMID- 17221968
TI  - Lewis-acid-catalyzed rearrangement of arylvinylidenecyclopropanes: significant
      influence of substituents and electronic nature of aryl groups.
AB  - Lewis-acid-catalyzed reactions of arylvinylidenecyclopropanes having three
      substituents at the corresponding cyclopropyl rings have been investigated
      thoroughly. The reaction products are highly dependent on the substituents at the
      corresponding cyclopropyl rings and the electronic nature of the aryl groups. For
      arylvinylidenecyclopropanes bearing two alkyl groups at the C-1 position (R1, R2,
      R3=aryl; R4=H; R5, R6=alkyl), naphthalene derivatives were formed in the presence
      of Lewis-acid Eu(OTf)3 in DCE at 40 degrees C. For arylvinylidenecyclopropanes in
      which R1, R2, R3=aryl and R4, R5=alkyl (syn/anti isomeric mixtures), the
      corresponding 6aH-benzo[c]fluorine derivatives were formed in the syn
      configuration via a double intramolecular Friedel-Crafts reaction when all of the
      aryl groups do not have electron-withdrawing groups or the corresponding indene
      derivatives were obtained via an intramolecular Friedel-Crafts reaction as long
      as one electron-deficient aryl group was attached. For
      arylvinylidenecyclopropanes in which R1, R2, R3, R4=aryl and R5=alkyl or H, the
      corresponding indene derivatives were obtained exclusively via a sterically
      demanding intramolecular Friedel-Crafts reaction. Lewis-acid effects and
      mechanistic insights have been discussed on the basis of experimental
      investigations.

PMID- 17221969
TI  - Imidazolium ionic liquids as solvents for cerium(IV)-mediated oxidation
      reactions.
AB  - Use of imidazolium ionic liquids as solvents for organic transformations with
      tetravalent cerium salts as oxidizing agents was evaluated. Good solubility was
      found for ammonium hexanitratocerate(IV) (ceric ammonium nitrate, CAN) and
      cerium(IV) triflate in 1-alkyl-3-methylimidazolium triflate ionic liquids.
      Oxidation of benzyl alcohol to benzaldehyde in 1-ethyl-3-methylimidazolium
      triflate was studied by in-situ FTIR spectroscopy and 13C NMR spectroscopy on
      carbon-13-labeled benzyl alcohol. Careful control of the reaction conditions is
      necessary because ammonium hexanitratocerate(IV) dissolved in an ionic liquid can
      transform benzyl alcohol not only into benzaldehyde but also into benzyl nitrate
      or benzoic acid. The selectivity of the reaction of cerium(IV) triflate with
      benzyl alcohol in dry ionic liquids depends on the degree of hydration of
      cerium(IV) triflate: anhydrous cerium(IV) triflate transforms benzyl alcohol into
      dibenzyl ether, whereas hydrated cerium(IV) triflate affords benzaldehyde as the
      main reaction product. Reactions of ammonium hexanitratocerate(IV) with organic
      substrates other than benzyl alcohol have been explored. 1,4-Hydroquinone is
      quantitatively transformed into 1,4-quinone. Anisole and naphthalene are
      nitrated. For the cerium-mediated oxidation reactions in ionic liquids, high
      reaction temperatures are an advantage because under these conditions smaller
      amounts of byproducts are formed.

PMID- 17221970
TI  - Oxidation of peptides by methyl(trifluoromethyl)dioxirane: the protecting group
      matters.
AB  - Representative Boc-protected and acetyl-protected peptide methyl esters bearing
      alkyl side chains undergo effective oxidation using
      methyl(trifluoromethyl)dioxirane (1b) under mild conditions. We observe a
      protecting group dependency in the chemoselectivity displayed by the dioxirane
      1b. N-Hydroxylation occurs in the case of the Boc-protected peptides, and side
      chain hydroxylation takes place in the case of acetyl-protected peptides. Both
      are attractive transformations since they yield derivatized peptides that serve
      as valuable synthons.

PMID- 17221971
TI  - Addition of difluorocarbene to 3',4'-unsaturated nucleosides: synthesis of 2'
      deoxy analogues with a 2-oxabicyclo[3.1.0]hexane framework.
AB  - Treatment of protected 2'-deoxy-3',4'-unsaturated nucleosides derived from
      adenosine and uridine with difluorocarbene [generated from
      bis(trifluoromethyl)mercury and sodium iodide] gave fused-ring 2,2
      difluorocyclopropane compounds. Stereoselective alpha-face addition to the
      dihydrofuran ring resulted from hindrance by the protected beta-anomeric
      nucleobases. A protected uracil compound was converted smoothly into the cytosine
      derivative via a 4-(1,2,4-triazol-1-yl) intermediate. Removal of the protecting
      groups gave new difluorocyclopropane-fused nucleoside analogues. The solid-state
      conformation of the nearly planar furanosyl ring in the uracil compound had a
      shallow 2E pucker, and a more pronounced 1E conformation was present in the
      furanosyl ring of the cytosine derivative.

PMID- 17221973
TI  - Remarkable efficiency of the aryne chemistry of
      (dehydro)octafluoro[2.2]paracyclophane when using the Cadogan method.
AB  - Generation of the aryne, (dehydro)octafluoro[2.2]paracyclophane, from its
      acetamide derivative utilizing the Cadogan method led to remarkable results with
      respect to Diels-Alder and ene reactivity. A comparison was made between this new
      and virtually unused method and our earlier reported results using Cram
      methodology (reaction of aryl iodide with potassium tert-butoxide). Surprisingly,
      no ene reactivity was observed with the Cram methodology. This mechanistic
      conundrum was examined extensively with no unambiguous explanation for the
      difference in reactivity being found.

PMID- 17221972
TI  - Acid-promoted cyclization reactions of tetrahydroindolinones. Model studies for
      possible application in a synthesis of selaginoidine.
AB  - The synthesis of various substituted bicyclic lactams by an acid-induced Pictet
      Spengler reaction of tetrahydroindolinones bearing tethered heteroaromatic rings
      is presented. The outcome of the cyclization depends on the position of the furan
      tether, tether length, nature of the tethered heteroaromatic ring, and the
      substituent group present on the 5-position of the tethered heteroaryl group. A
      one-pot procedure was developed to efficiently prepare tetrahydroindolinones
      containing tethered furan rings. In a typical example, the reaction of furanyl
      azide 26 with n-Bu3P delivered iminophosphorane 27, which was allowed to react
      with a 1-alkyl-(2-oxocyclohexyl)acetic acid to provide the desired furanyl
      substituted tetrahydroindolinone system 29. Treatment of 29 with trifluoroacetic
      acid afforded the tetracyclic lactam skeleton 30 found in the alkaloid (+/-)
      selaginoidine.

PMID- 17221974
TI  - Methyl substituent effects in radical cation Diels-Alder reactions.
AB  - The effect of methyl substitution on the Diels-Alder radical cation reaction was
      studied using B3LYP with a 6-31G* basis set. Five separate pathways, one
      concerted and four stepwise, were examined for each possible position of a methyl
      substituent. None of the concerted transition structures could be located without
      symmetry constraints, and all but one of the structures obtained under these
      conditions were destabilized by a second-order Jahn-Teller distortion. A
      concerted pathway with simultaneous bond formation at C1 and C4 is therefore
      excluded. Stepwise pathways that had the methyl group either on a carbon involved
      in the initial bond formation or in a position where it could not stabilize the
      radical/cation were a few kcal/mol above alternate pathways. High transition
      state energies for the formation of vinylcyclobutane derivatives cause it to be a
      minor product in general. The pathway that proceeds through an anti-intermediate
      is the most favored, while the pathways forming the gauche-out intermediate that
      converts to the anti-intermediate is also strongly represented. Both of the major
      pathways lead directly to the formation of the methylcyclohexene product.

PMID- 17221975
TI  - Dicobaltoctacarbonyl-mediated synthesis of tricyclic 5,6-diydropyran-2-one
      derivatives via tandem cycloaddition reaction between cis-epoxyalkynes, a
      tethered olefin, and carbon monoxide.
AB  - Cobalt carbonyl complex Co2(CO)8 implemented an intramolecular carbonylation of
      cis-epoxyalkynes to generate Co2(CO)6-stabilized gamma-lactonyl allene species.
      For 1,1,2-trisubstituted epoxyalkynes, this Co2(CO)6-allene species reacted with
      a tethered olefin to give [2+2]-cycloadducts, and with CO and a tethered olefin
      to produce [2+2+1]-cycloadducts. These resulting cycloadducts have a 5,6
      diydropyran-2-one core fused with a cyclobutane and a cyclopentanone ring,
      respectively. For 1,2-disubstituted cis-epoxyalkyne and 1,1,2-trisubstituted cis
      epoxyalkynes bearing a heteroatom constituent, cyclization of the corresponding
      epoxyalkyne with a tethered alkene is invariably accompanied by incorporation of
      CO to produce a [2+2+1]-cycloadduct, even in the absence of CO. We have prepared
      various 1,1,2-trisubstituted and 1,2-disubstituted cis-epoxyalkynes to generalize
      such cycloaddition pathways. Attempt to use an organic promoter to perform these
      tandem cycloadditions was unsuccessful because of a competing Pauson-Khand
      reaction. Cyclization of a 1,2-disubstituted epoxyalkyne with a tethered diene
      was achieved successfully in one case, but the yield was low (25%).

PMID- 17221978
TI  - Quantitative evaluation of the mechanism of electroreduction of benzoyl cyanides.
AB  - The mechanism of reduction of benzoyl cyanide, 6, p-methoxybenzoyl cyanide, 7,
      and p-chlorobenzoyl cyanide, 8, has been studied in acetonitrile (6 and 7), N,N
      dimethylformamide (6), and acetonitrile containing water (all three compounds).
      The reaction proceeds by initial reduction to form the anion radical followed by
      dimerization to produce an intermediate dianion, the dianion of the dicyanohydrin
      of benzil. The latter loses cyanide to give the anion of the monocyanohydrin of
      benzil, which undergoes two parallel reactions: expulsion of cyanide to give the
      corresponding benzil and rearrangement to the monoanion of mandelonitrile
      benzoate. The addition of water brings about an increase in the dimerization rate
      constant and an associated increase in the amount of benzil that is produced. The
      standard potentials for the initial reduction step have been evaluated, and their
      dependence on the substituent is discussed. The dimerization rate constants have
      also been evaluated.

PMID- 17221976
TI  - Aryl amidation routes to dihydropyrrolo[3,2-e]indoles and pyrrolo[3,2
      f]tetrahydroquinolines: total synthesis of the (+/-)-CC-1065 CPI subunit.
AB  - CC-1065 and the related duocarmycins are members of a structurally unique family
      of naturally occurring molecules and remain some of the most rigorously studied
      antitumor compounds to date. Herein we describe a total synthesis of the (+/-)-CC
      1065 CPI subunit in an overall yield of 9.3% from commercially available 5-fluoro
      2-nitrophenol. The key steps of this synthesis are a Diels-Alder reaction of an o
      benzoxy-monoimine quinoid and an intramolecular aryl triflate amidation, which
      formed the pyrrolo[3,2-f]tetrahydroquinoline intermediate en route to CPI.

PMID- 17221977
TI  - Synthesis of xanthones, thioxanthones, and acridones by the coupling of arynes
      and substituted benzoates.
AB  - The reaction of silylaryl triflates, CsF, and ortho-heteroatom-substituted
      benzoates affords a general and efficient way to prepare biologically interesting
      xanthones, thioxanthones, and acridones. This chemistry presumably proceeds by a
      tandem intermolecular nucleophilic coupling of the benzoate with an aryne and a
      subsequent intramolecular electrophilic cyclization.

PMID- 17221979
TI  - Synthesis and properties of benzophenone-spiropyran and naphthalene-spiropyran
      conjugates.
AB  - We have designed and synthesized four compounds integrating luminescent and
      photochromic components in their molecular skeletons. Two of them combine a
      nitrospiropyran photochrome with either one or two naphthalene fluorophores and
      can be prepared in three synthetic steps. The other two consist of a
      nitrospiropyran photochrome and a benzophenone phosphore connected by either
      ether or ester linkages and can be prepared in six or five, respectively,
      synthetic steps. The luminescent components of these assemblies are expected to
      transfer energy intramolecularly to the photochromic species upon excitation and
      encourage their photoisomerization. Consistently, the phosphorescence of the
      benzophenone units and the fluorescence of the naphthalene components are
      effectively quenched when these species are connected covalently to a
      nitrospiropyran. Nonetheless, the photoisomerization of the photochrome becomes
      significantly less efficient after the covalent attachment to the luminescent
      partner. The fraction of incident radiations absorbed by either the benzophenone
      or the naphthalene fragment does not promote the isomerization of the
      photochromic appendage. Instead, irreversible transformations occur upon
      irradiation of the luminophore-photochrome assemblies. Thus, the covalent
      attachment of a benzophenone or a naphthalene to a nitrospiropyran is not a
      viable strategy to improve the photocoloration efficiency of the photochromic
      component. Even although the very same luminophores are known to sensitize
      intermolecularly the isomerization of nitrospiropyrans, the transition to
      covalent luminophore-photochrome assemblies tends to promote degradation, rather
      than sensitization, upon irradiation.

PMID- 17221980
TI  - Telluroxides exhibit hydrolysis capacity.
AB  - It has long been known that tellurium compounds are rather toxic to living
      organisms, and tellurium has not been found in natural biomacromolecules to date.
      The principles of telluride toxicity in biological processes are still
      controversial partly because of the lack of information on the biochemical
      features of tellurium. In this contribution, we report our finding for the first
      time that telluroxides exhibit hydrolysis capacity. For instance, 6,6'-telluroxy
      bis(6-deoxy-beta-cyclodextrin) acts as a hydrolase mimic and shows a significant
      rate acceleration of 106,000 for the hydrolysis of 4,4'-dinitrodiphenyl
      carbonate.

PMID- 17221981
TI  - Multivalent macrocyclic hosts: histone surface recognition, guest binding, and
      delivery by cyclophane-based resorcinarene oligomers.
AB  - As a new class of host for both specific proteins and hydrophobic molecular
      guests, cyclophane-based resorcinarene oligomers were designed on the basis of a
      molecular design that allows the assembly of four or 12 anionic resorcinarenes on
      a cyclophane skeleton. We prepared a cyclophane-based resorcinarene tetramer (4),
      constructed with a tetraaza[6.1.6.1]-paracyclophane skeleton and four
      resorcinarenes bearing heptacarboxylic acid residues that connect to the
      macrocycle through amide linkages. In addition, we prepared an extended
      analogical dodecamer (12), which was constructed with a pentakis(cyclophane)
      skeleton and 12 resorcinarenes. The cyclophane-based resorcinarene oligomers
      exhibited potent recognition capabilities toward histone, a small basic protein
      of eukaryotic chromatins. The binding constants (K) of cyclophane-based
      resorcinarene tetramer 4 and dodecamer 12 with histone were determined to be
      1.3x107 and 8.4x107 M-1, respectively, by means of surface plasmon resonance
      measurements. The K values of 4 and 12 with histone were 31- and 200-fold larger
      than that of an untethered reference resorcinarene, reflecting the multivalency
      effects in resorcinarenes. In addition to that, cyclophane-based resorcinarene
      tetramer 4 and dodecamer 12 captured hydrophobic guests such as 6-p
      toluidinonaphthalene-2-sulfonate, with respective binding constants of 2.4x103
      and 2.5x104 M-1 in an aqueous HEPES buffer as evaluated by fluorescence
      spectroscopy. Furthermore, the resorcinarene oligomers were also found to act as
      guest carriers from the bulk aqueous phase to histone surfaces, as confirmed by
      fluorescence spectroscopy.

PMID- 17221982
TI  - Two-dimensional scaffolds for the parallel alignment of rod-shaped conjugated
      molecules.
AB  - Described is a method for creating two-dimensional, ordered arrays of linear,
      conjugated organic molecules on polyimide scaffolds. Key to the design was the
      enforcement of consecutive 90 degrees twist angles along the polyimide backbone.
      Rod molecules that are templated by such scaffolds are held parallel and in the
      same plane and have optical properties that are similar to those of monomeric
      analogues. As supporting evidence for the structures of the polymers, a series of
      model compounds were synthesized and characterized by X-ray crystallography. The
      polymeric materials are soluble and have been characterized by 1H NMR, 13C NMR,
      MALDI-TOF, and UV-vis spectroscopy.

PMID- 17221984
TI  - Facile synthesis of N-dialkylaminomethyl-substituted heterocycles.
AB  - Iminium ions are generated by treatment of aminals with succinic anhydride. These
      iminium ions are trapped by heterocycles, giving the corresponding N-dialkylamino
      methyl-substituted heterocycles, which are easily separated from the succinic
      acid monoamide byproducts by means of an aqueous base wash. The heterocyclic
      products are obtained in good yield and in a high state of purity without need of
      recrystallization or distillation.

PMID- 17221983
TI  - One-pot asymmetric synthesis of either diastereomer of tert-butanesulfinyl
      protected amines from ketones.
AB  - A one-pot method for the asymmetric synthesis of tert-butanesulfinyl-protected
      amines is described. Condensation of aryl alkyl and dialkyl ketones with tert
      butanesulfinamide followed by in situ reduction with the appropriate reagent
      provides either diastereomer of the sulfinamide products in good yields and with
      diastereomeric ratios of up to 99:1.

PMID- 17221985
TI  - Structures of the intermediates formed in the ring-opening reaction of 2-chloro-3
      nitropyridine.
AB  - The reaction of 2-chloro-3-nitropyridine with two equivalents of hydroxide ion
      was studied by NMR and X-ray crystallography. On the basis of NMR coupling
      constants, the originally formed ring-opened intermediate is the pseudo-cis form,
      as predicted by the SN(ANRORC) mechanism. However, the first intermediate is
      unstable and isomerizes to a second intermediate, which was isolated. The pseudo
      trans geometry of the second intermediate [3-pentenenitrile, 2-nitro-5-oxo, ion(
      1), sodium] explains why additional base does not lead to the ring-closing
      reaction as observed with 2-chloro-5-nitropyridine.

PMID- 17221987
TI  - Bidirectional, organocatalytic synthesis of lepidopteran sex pheromones.
AB  - Shuffling of two simple building blocks and a regioselective transfer
      hydrogenation allow for the rapid synthesis of a small collection of lepidopteran
      sex pheromones, e.g., 8E,10Z-tetradeca-8,10-dienal 5c, from the horse chestnut
      leafminer (Cameraria ohridella).

PMID- 17221986
TI  - Enforcing periodic secondary structures in hybrid peptides: a novel hybrid
      foldamer containing periodic gamma-turn motifs.
AB  - This note describes the design, synthesis, and conformational studies of a novel
      hybrid foldamer that adopts a definite compact, three-dimensional structure
      determined by a combined effect of the special conformational properties of the
      foldamer constituents. The striking feature of this de novo designed foldamer is
      its ability to display periodic gamma-turn conformations stabilized by
      intramolecular hydrogen bonds. Conformational investigations by single-crystal X
      ray studies, solution-state NMR, and ab initio MO theory at the HF/6-31G* level
      strongly support the prevalence of gamma-turn motifs in both the di- and
      tetrapeptide foldamers, which are presumably stabilized by bifurcated hydrogen
      bonds in the solid and solution states. The strategy disclosed herein for the
      construction of hybrid foldamers with periodic gamma-turn motifs has the
      potential to significantly augment the conformational space available for
      foldamer design with diverse backbone structures and conformations.

PMID- 17221988
TI  - Seven-membered cyclic sulfite eudesmane derivatives: partial synthesis,
      structural determination, and enzymatic resolution.
AB  - Two chromatographically inseparable, diastereomeric eudesmane cyclic sulfites
      have been semisynthesized from alpha-santonin. This diastereomeric mixture was
      resolved by enzymatic acetylation with CCL. Each cyclic sulfite derivative was
      individually characterized on the basis of its spectroscopic and crystallographic
      properties.

PMID- 17221989
TI  - Stereoselective formation of alpha-alkylidene cyclic carbonates via carboxylative
      cyclization of propargyl alcohols in supercritical carbon dioxide.
AB  - Carboxylative cyclization of propargyl alcohols in supercritical carbon dioxide
      (scCO2) containing P(n-C4H9)3 as a catalyst proceeded smoothly to give alpha
      alkylidene-1,3-dioxolan-2-ones. Internal propargyl alcohols afforded Z-alkyl
      idene cyclic carbonates exclusively. CO2 incorporation was markedly promoted
      under supercritical conditions, possibly due to the facile formation of a
      putative P(n-C4H9)3-CO2 adduct as a key intermediate.

PMID- 17221991
TI  - Amide bond cleavage: acceleration due to a 1,3-diaxial interaction with a
      carboxylic acid.
AB  - To independently assess the contribution of ground-state pseudoallylic strain to
      the enormous rates of amide bond cleavage in tertiary amide derivatives of Kemp's
      triacid, we have studied four amide derivatives of (1alpha-3alpha-5beta)-5-tert
      butyl-1,3-cyclohexanedicarboxylic acid. Our results demonstrate that absent
      pseudoallylic strain, a 1,3-diaxial interaction of an amide with a carboxylic
      acid leads to only a 2400-fold increase in the rate of amide bond cleavage as
      compared with the rate of hydrolysis of an unactivated peptide bond.

PMID- 17221990
TI  - 1,3-dipolar cycloadditions of trimethylsilyldiazomethane revisited: steric demand
      of the dipolarophile and the influence on product distribution.
AB  - The 1,3-dipolar cycloaddition of trimethylsilyldiazomethane with alpha,beta
      unsaturated esters was examined. The resulting 1-pyrazolines isomerize to
      regioisomeric 2-pyrazolines (a or b) or undergo desilylation (c). Acrylates yield
      only b or c. beta-Substituted dipolarophiles may yield all three types of
      products. This work demonstrates that the distribution of 2-pyrazoline products
      is highly dependent on the relative configuration of the substituents on the 1
      pyrazoline intermediate.

PMID- 17221992
TI  - Intermolecular electrophilic O-amination of alcohols.
AB  - We report the first examples of an intermolecular electrophilic O-amination of
      aliphatic alcohols. Thus, the new reagents, fluorenone oxime tosylate, 5a, or
      mesylate, 5b, permit O-amination of diverse alcohols in the presence of NaH under
      mild conditions. By following the formation of the resulting oxime ethers, 6, the
      reaction was shown to be sensitive to steric effects in the alcohol. Furthermore,
      the presence of an aromatic ring or of a double bond in the alcohol molecule
      (benzyl, allyl) was found to increase the reaction rate.

PMID- 17221993
TI  - o-Iodoxybenzoic acid- and tetraethylammonium bromide-mediated oxidative
      transformation of primary carboxamides to one-carbon dehomologated nitriles.
AB  - A clean and efficient method for the oxidative transformations of primary
      carboxamides to one-carbon dehomologated nitriles using the combination of o
      iodoxybenzoic acid and tetraethylammonium bromide has been developed. This method
      exhibits a broad scope and is expected to be of great utility in organic
      synthesis.

PMID- 17221994
TI  - Concise synthesis of rodgersinol and determination of the C-10 absolute
      configuration.
AB  - Rodgersinol was synthesized via seven linear steps in 31% overall yield, and the
      absolute configuration of the C-10 stereogenic center was elucidated. The key
      feature of the synthesis involves the efficient Cu(II)-mediated coupling of two
      aromatic moieties for the diaryl ether intermediate and the enantioselective
      construction of the hydroxypropyl substituent by a regio- and stereoselective
      methyl addition to the chiral aryloxiranes in an inversion manner.

PMID- 17221995
TI  - Spontaneous enzymatically mediated dynamic kinetic resolution of 8-amino-5,6,7,8
      tetrahydroquinoline.
AB  - A spontaneous dynamic kinetic resolution of 8-amino-5,6,7,8-tetrahydroquinoline 1
      was observed in the presence of Candida antarctica Lipase B, in which a >60%
      yield of (R)-acetamide [(R)-2] was isolated from the racemic amine. The
      spontaneous formation of ketone 3, followed by a condensation/hydrolysis sequence
      with the remaining (S)-amine 1, via enamine 4, provides the necessary
      racemization pathway.

PMID- 17221996
TI  - CuBr/rac-BINOL-catalyzed N-arylations of aliphatic amines at room temperature.
AB  - We have developed an efficient and readily available catalyst system CuBr/racemic
      BINOL (1,1'-binaphthyl-2,2'-diol) that catalyzes N-arylation of aliphatic amines
      at room temperature, and this inexpensive catalyst system is of high selectivity
      and tolerance toward various functional groups in the substrates.

PMID- 17221997
TI  - Synthesis of the isonicotinoylnicotinamide scaffolds of the naturally occurring
      isoniazid-NAD(P) adducts.
AB  - The first syntheses of the 1-hydroxy-1-(pyridin-4-yl)-1,2-dihydro-3H-pyrrolo[3,4
      c]pyridin-3-one heterocycle and the 3-aminocarbonyl-4-isonicotinoyl-1,4
      dihydropyridine framework present in the isoniazid-NAD(P) adducts are described.

PMID- 17221998
TI  - Practical synthesis of azobenzenophanes.
AB  - We devised a practical synthetic route to azobenzenophanes via successive Cu- and
      Pd-catalyzed coupling reaction of aryl hydrazide and aryl halide followed by
      Cu(I)-mediated oxidation reaction.

PMID- 17221999
TI  - Expedient synthesis of sulfinamides from sulfonyl chlorides.
AB  - Sulfinamides were synthesized from sulfonyl chlorides using a procedure involving
      in situ reduction of sulfonyl chlorides. The reaction is broad in scope and easy
      to perform.

PMID- 17222001
TI  - Genotyping of single-nucleotide polymorphisms by primer extension reaction in a
      dry-reagent dipstick format.
AB  - The primer extension (PEXT) reaction is the most widely used approach to
      genotyping of single-nucleotide polymorphisms (SNPs). Current methods for
      analysis of PEXT reaction products are based on electrophoresis, fluorescence
      resonance energy transfer, fluorescence polarization, pyrosequencing, mass
      spectrometry, microarrays, and spectrally encoded microspheres. We report the
      first dry-reagent dipstick method that enables rapid visual detection of PEXT
      products without instrumentation. The method is applied to the analysis of six
      SNPs in the mannose-binding lectin gene (MBL2). The genomic region that spans
      each SNP of interest is amplified by PCR. Two primer extension reactions are
      performed with allele-specific primers (for one or the other variant nucleotide),
      which contain an oligo(dA) segment at the 5'-end. Biotin-dUTP is incorporated in
      the extended strand. The product is applied to the strip followed by immersion in
      the appropriate buffer. As the DNA moves along the strip by capillary action, it
      hybridizes with oligo(dT)-functionalized gold nanoparticles, such that only
      extended products are captured by immobilized streptavidin at the test zone,
      generating a red line. A second red line is formed at the control zone of the
      strip by hybridization of the nanoparticles with immobilized oligo(dA). The
      dipstick test is complete within 10 min. We analyzed six SNPs of the mannose
      binding lectin gene (MBL2) using genomic DNA from 27 patients, representing a
      total of 74 variant nucleotide positions. Patient genotypes showed 100%
      concordance with direct DNA sequencing data. The described PEXT-dipstick assay is
      rapid and highly accurate; it does not require specialized instrumentation or
      highly trained technical personnel. It is appropriate for a diagnostic laboratory
      where a few selected SNP markers are examined per patient with a low cost per
      assay.

PMID- 17222002
TI  - Integrative metabolomics for characterizing unknown low-abundance metabolites by
      capillary electrophoresis-mass spectrometry with computer simulations.
AB  - Characterization of unknown low-abundance metabolites in biological samples is
      one the most significant challenges in metabolomic research. In this report, an
      integrative strategy based on capillary electrophoresis-electrospray ionization
      ion trap mass spectrometry (CE-ESI-ITMS) with computer simulations is examined as
      a multiplexed approach for studying the selective nutrient uptake behavior of E.
      coli within a complex broth medium. On-line sample preconcentration with
      desalting by CE-ESI-ITMS was performed directly without off-line sample
      pretreatment in order to improve detector sensitivity over 50-fold for cationic
      metabolites with nanomolar detection limits. The migration behavior of charged
      metabolites were also modeled in CE as a qualitative tool to support MS
      characterization based on two fundamental analyte physicochemical properties,
      namely, absolute mobility (muo) and acid dissociation constant (pKa). Computer
      simulations using Simul 5.0 were used to better understand the dynamics of
      analyte electromigration, as well as aiding de novo identification of unknown
      nutrients. There was excellent agreement between computer-simulated and
      experimental electropherograms for several classes of cationic metabolites as
      reflected by their relative migration times with an average error of <2.0%. Our
      studies revealed differential uptake of specific amino acids and nucleoside
      nutrients associated with distinct stages of bacterial growth. Herein, we
      demonstrate that CE can serve as an effective preconcentrator, desalter, and
      separator prior to ESI-MS, while providing additional qualitative information for
      unambiguous identification among isobaric and isomeric metabolites. The proposed
      strategy is particularly relevant for characterizing unknown yet biologically
      relevant metabolites that are not readily synthesized or commercially available.

PMID- 17222003
TI  - Method for stabilizing protein-ligand complexes in nanoelectrospray ionization
      mass spectrometry.
AB  - The interaction between the bovine pancrease trypsin (Tryp) and its competitive
      inhibitor benzamidine (1), in solution and the gas phase, is investigated using
      nanoflow electrospray ionization (nanoES) and Fourier transform ion cyclotron
      resonance mass spectrometry. In a recent study (Clark, S.M.; Konermann L. Anal.
      Chem. 2004, 76, 7077-7083), it was reported that the (Tryp + 1) complex could not
      be detected by ES-MS. Here, it is shown that, with gentle sampling conditions, it
      is possible to detect gaseous protonated ions of the (Tryp + 1) complex with
      nanoES-MS. However, the relative abundance of the detected (Tryp + 1)n+ ions is
      lower than expected, based on solution composition, which suggests that
      dissociation of (Tryp + 1)n+ ions occurs during MS sampling. The dissociation
      pathways and corresponding Arrhenius parameters for the protonated (Tryp + 1)n+
      ions, at n = 7-9, are determined from time-resolved thermal dissociation
      experiments, implemented with the blackbody infrared radiative dissociation
      technique. The gaseous (Tryp + 1)n+ ions are found to have short lifetimes, e.g.,
      <0.6 s, at temperatures of >100 degrees C. The use of solution additives,
      including polyols, carbohydrates, amino acids, and small organic molecules, to
      stabilize the (Tryp + 1)n+ ions during nanoES-MS analysis is investigated.
      Notably, the addition of imidazole to the nanoES solution is shown to preserve
      the (Tryp + 1)n+ ions. The Kassoc value, (1.9 +/- 0.2) x 104 M-1, determined for
      the (Tryp + 1) complex by the direct ES-MS method is in agreement with values
      determined by other analytical methods. The stabilizing effect of imidazole in
      nanoES-MS is further demonstrated for the interaction between carbonic anhydrase
      II and 5-(dimethylamino)naphthalene-1-sulfonamide. The stabilizing effect of
      imidazole may be due to enhanced evaporative cooling achieved by the dissociation
      of molecules of imidazole, bound nonspecifically, from the protein-ligand complex
      in the ion source.

PMID- 17222004
TI  - DNA detection on plastic: surface activation protocol to convert polycarbonate
      substrates to biochip platforms.
AB  - A mild and efficient surface activation protocol to convert polycarbonate (PC)
      substrates, e.g., plastic bases of compact disks, to biochip platforms for DNA
      probe immobilization and target detection is described. The preparation procedure
      (activation, patterning, and coupling) is simple and effective; the on-chip
      hybridization is sensitive and selective. Particularly, UV/ozone treatment of PC
      sheets produces a hydrophilic surface with a high density of reactive carboxylic
      acid groups [(4.8 +/- 0.2) x 10-10 mol/cm2] in less than 10 min at ambient
      conditions, and no significant aging or physical damage to the substrate is
      observed. Covalent immobilization of DNA probes via both passive (reagent-less
      photopatterning and coupling in bulk solution phase) and flow-through (creation
      of microarrays with microfluidic channel plates) procedures has been
      demonstrated. Subsequent hybridization shows uniform and strong fluorescent
      signals for complementary target DNA and allows clear discrimination between
      fully complementary targets and strands with a single base-pair mismatch. The
      surface chemistry described herein will facilitate the development of disposable
      plastic biochips (not limited to DNA microarrays) and the fabrication of
      biomedical devices that are readable with conventional optical drives.

PMID- 17222005
TI  - Small-molecule analysis with silicon-nanoparticle-assisted laser
      desorption/ionization mass spectrometry.
AB  - Silicon nanopowder (5-50 nm) was applied as a matrix for the analysis of small
      molecules in laser desorption/ionization mass spectrometry. In contrast with
      conventional matrix-assisted laser desorption/ionization (MALDI) time-of-flight
      mass spectrometry, the matrix background interference in the low mass range was
      significantly reduced. Effects of the particle size and sample preparation
      procedures on the background mass spectra and the analyte signal intensity have
      been investigated, and an optimized powder and sample preparation protocol was
      established. Several surface characterization tools have been applied as well.
      Both positive mode and negative mode laser desorption/ionization have been
      applied to different analytes including drugs, peptides, pesticides, acids, and
      others. Detection limits down to the low femtomole per microliter levels were
      achieved for propafenone and verapamil drugs. The method developed was found
      relatively tolerant to salt contamination, which allowed the direct analysis of
      morphine and propaphenone in untreated urine and triazine herbicides in a soil
      extract. The new silicon-nanoparticle-assisted laser desorption ionization method
      was found to be highly selective, which may be due to analyte-dependent
      precharging in solution, prior to vacuum laser desorption. Some aspects of the
      charge-transfer mechanism have been studied and discussed. In comparison with
      standard MALDI matrixes, the silicon nanopowder requires much lower laser fluence
      (contributing to a reduced background) has much better surface homogeneity, and
      is more tolerant to salt interference, which makes it an easily applicable
      practical tool at a potentially low cost.

PMID- 17222007
TI  - Detection of NADH and ethanol based on catalytic activity of soluble carbon
      nanofiber with low overpotential.
AB  - The excellent catalytic activity of a novel carbon nanomaterial, soluble carbon
      nanofiber (CNF) with good dispersion and wettability, to the oxidation of
      dihydronicotinamide adenine dinucleotide (NADH) was described for biosensing
      application. The edge plane sites and oxygen-rich groups presented on the CNF
      surface could be partially responsible for its electrocatalytic behavior, which
      induced a substantial decrease by 573 mV in the overpotential of NADH oxidation
      reaction (compared to a bare electrode). The CNF-coated electrode thus allowed
      highly sensitive amperometric detection of NADH with a low limit of detection
      (0.11 muM), low applied potential (+0.06 V), and minimization of surface fouling.
      Such ability of CNF to promote the electron transfer between NADH and the
      electrode suggested a new, promising biocompatible platform for development of
      dehydrogenase-based amperometric biosensors. With alcohol dehydrogenase (ADH) as
      a model, the ADH/CNF-modified electrode could be constructed by a simple casting
      process. The proposed biosensor showed rapid and highly sensitive amperometric
      response to ethanol with acceptable preparation reproducibility and excellent
      stability.

PMID- 17222006
TI  - Glucose recovery with bare and hydrogel-coated microdialysis probes: experiment
      and simulation of temporal effects.
AB  - In vitro microdialysis glucose sampling was used to test the transient and steady
      state suitability of antifouling hydrogel coatings, composed of 2-hydroxyethyl
      methacrylate, vinylpyrrolidinone, and poly(ethylene glycol). The in vitro glucose
      diffusion coefficients of bare microdialysis membranes and hydrogel coatings were
      determined experimentally to be 1.1 x 10-6 and 3.2 x 10-6 cm2/s, respectively.
      These values were used to numerically simulate the effect of the hydrogel on
      glucose transport across the microdialysis membrane using a convection-diffusion
      transport model. The times for dialysate at the exit of the bare and hydrogel
      coated microdialysis probes to reach 95% of steady state were calculated to be 20
      and 66 s, respectively. However, the experimental data showed that 95% of steady
      state glucose recoveries were reached after 4-5 min. Numerical simulations
      incorporating the Taylor dispersion in the outlet tubing showed the time
      difference was caused almost completely by convective transport in the outlet
      tubing with negligible contribution from analyte profile broadening. These data
      indicated that the hydrogel coatings imposed 44% reduction in glucose
      permeability and consequently 26% reduction in the percent recovery. The effect
      of hydrogel coatings on the time to reach the steady-state recovery was
      insignificant compared with the time required for convection of glucose in the
      outlet tubing.

PMID- 17222008
TI  - Electrogenerated chemiluminescence. 83. Immunoassay of human C-reactive protein
      by using Ru(bpy)3(2+)-encapsulated liposomes as labels.
AB  - Liposomes ( approximately 100-nm diameter) containing Ru(bpy)32+ (bpy = 2,2'
      bipyridine) were prepared as an electrogenerated chemiluminescent (ECL) tag for a
      sandwich-type immunoassay of human C-reactive protein (CRP). Polyclonal human CRP
      antibodies were introduced onto liposomes and magnetic beads through biotin
      streptavidin interaction. The antigen-antibody conjugates formed on addition of a
      CRP-containing sample were separated from unreacted species magnetically.
      Addition of 0.1 M tri-n-propylamine and 0.1 M phosphate buffer (pH 7.6)
      containing 0.1 M NaCl and 1% (v/v) Triton X-100 caused liberation of the
      Ru(bpy)32+ from the liposome. ECL obtained in this medium showed a detection
      limit of 100 ng/mL for human CRP with good linearity of ECL intensity versus
      antigen concentration over the range 100 ng/mL-10 microg/mL.

PMID- 17222009
TI  - Closed-loop, multiobjective optimization of two-dimensional gas
      chromatography/mass spectrometry for serum metabolomics.
AB  - Metabolomics seeks to measure potentially all the metabolites in a biological
      sample, and consequently, we need to develop and optimize methods to increase
      significantly the number of metabolites we can detect. We extended the closed
      loop (iterative, automated) optimization system that we had previously developed
      for one-dimensional GC-TOF-MS (O'Hagan, S.; Dunn, W. B.; Brown, M.; Knowles, J.
      D.; Kell, D. B. Anal. Chem. 2005, 77, 290-303) to comprehensive two-dimensional
      (GCxGC) chromatography. The heuristic approach used was a multiobjective version
      of the efficient global optimization algorithm. In just 300 automated runs, we
      improved the number of metabolites observable relative to those in 1D GC by some
      3-fold. The optimized conditions allowed for the detection of over 4000 raw
      peaks, of which some 1800 were considered to be real metabolite peaks and not
      impurities or peaks with a signal/noise ratio of less than 5. A variety of
      computational methods served to explain the basis for the improvement. This
      closed-loop optimization strategy is a generic and powerful approach for the
      optimization of any analytical instrumentation.

PMID- 17222011
TI  - Monolithic porous polymer layer for the separation of peptides and proteins using
      thin-layer chromatography coupled with MALDI-TOF-MS.
AB  - Plates for thin-layer chromatography (TLC) with an attached layer of porous
      polymer monolith have been prepared and used for the separation of small
      molecules, peptides, and proteins. The 50-200-mum. thin poly(butyl methacrylate
      co-ethylene dimethacrylate) layers were prepared in situ using UV-initiated
      polymerization. Precise control of the reaction conditions enables the
      preparation of monolithic layers with a well-defined porous structure that
      determines the chromatographic performance. Compared to conventional TLC and high
      performance TLC using precoated layers based on silica, the small layer thickness
      and absence of any binder is expected to improve both retention characteristics
      and separation efficiency of the polymer-based monolithic thin-layer
      chromatographic plates. Spots of the separated compounds were first detected
      using typical UV imaging. Since the monolithic thin layers can be also prepared
      directly on the stainless steel MALDI carrier plate, the separation in TLC format
      can be coupled with MALDI-TOF-MS. Application of a conventional MALDI matrix
      facilitated desorption and ionization of peptides and proteins for molecular
      weight determination of the separated compounds.

PMID- 17222010
TI  - Supplemental activation method for high-efficiency electron-transfer dissociation
      of doubly protonated peptide precursors.
AB  - Electron-transfer dissociation (ETD) delivers the unique attributes of electron
      capture dissociation to mass spectrometers that utilize radio frequency trapping
      type devices (e.g., quadrupole ion traps). The method has generated significant
      interest because of its compatibility with chromatography and its ability to: (1)
      preserve traditionally labile post-translational modifications (PTMs) and (2)
      randomly cleave the backbone bonds of highly charged peptide and protein
      precursor ions. ETD, however, has shown limited applicability to doubly
      protonated peptide precursors, [M + 2H]2+, the charge and type of peptide most
      frequently encountered in "bottom-up" proteomics. Here we describe a supplemental
      collisional activation (CAD) method that targets the nondissociated (intact)
      electron-transfer (ET) product species ([M + 2H]+*) to improve ETD efficiency for
      doubly protonated peptides (ETcaD). A systematic study of supplementary
      activation conditions revealed that low-energy CAD of the ET product population
      leads to the near-exclusive generation of c- and z-type fragment ions with
      relatively high efficiency (77 +/- 8%). Compared to those formed directly via
      ETD, the fragment ions were found to comprise increased relative amounts of the
      odd-electron c-type ions (c+*) and the even-electron z-type ions (z+). A large
      scale analysis of 755 doubly charged tryptic peptides was conducted to compare
      the method (ETcaD) to ion trap CAD and ETD. ETcaD produced a median sequence
      coverage of 89%-a significant improvement over ETD (63%) and ion trap CAD (77%).

PMID- 17222012
TI  - Effect of cluster size in kiloelectronvolt cluster bombardment of solid benzene.
AB  - Emission of benzene molecules by 5-keV cluster bombardment of a range of carbon
      projectiles from C6H6 to C180 is studied by a coarse-grained molecular dynamics
      (MD) technique. This approach permits calculations that are not feasible using
      more complicated potential energy functions, particularly as the interesting
      physics associated with the ion impact event approaches the mesoscale. These
      calculations show that the highest ejection yields are associated with clusters
      that deposit their incident energy 15-20 A below the surface. The highest yield
      for the projectiles is produced by the C20 and C60 projectiles. The results from
      the MD simulations are also compared favorably to an analytical model based on
      fluid dynamics to describe the energy deposition. The analytical model is then
      utilized to extend the range of the calculations to higher incident energies. The
      issue of the relative amount of chemical fragmentation and intact molecular
      desorption is also examined for the benzene crystal. These results show that
      damage accumulation at high-incident fluence should not be problematic and that
      it should be possible to perform molecular depth profiling via secondary ion mass
      spectrometry experiments. In general, the approach presented here illustrates the
      power of combining a simplified MD method with analytical strategies for
      describing a length scale that is difficult to achieve with traditional MD
      calculations.

PMID- 17222013
TI  - Reusable platinum nanoparticle modified boron doped diamond microelectrodes for
      oxidative determination of arsenite.
AB  - Boron doped diamond (BDD) macro- and microelectrodes were modified by
      electrodeposition of platinum nanoparticles using a multipotential step
      electrodeposition technique and used for the oxidative determination of arsenite,
      As(III). The formation of Pt nanoparticles was evident from cyclic voltammetry
      measurement, whereas AFM and SEM revealed the size and size distribution of
      deposited Pt nanoparticles. Raman spectroscopy illustrated a correlation between
      the typical BDD signature and the number of platinum deposition cycles. Linear
      sweep voltammetry performed with the modified BDD microelectrode outperformed its
      macrocounterpart and resulted in very low detecting currents with enhanced signal
      to-noise ratios. With linearity up to 100 ppb and a detection limit of 0.5 ppb,
      the electrochemical system was applicable for processing tap and river water
      samples. Over 150 repetitive runs could be performed, and electrochemical etching
      of platinum allowed the reuse of the BDD microelectrode. The presence of copper
      and chloride ions, the two most severe interferents at levels commonly found in
      groundwater, did not interfere with the assay.

PMID- 17222014
TI  - Detection of in situ derivatized peptides in microbial biofilms by laser
      desorption 7.87 eV postionizaton mass spectrometry.
AB  - A novel analytical method based on laser desorption postionization mass
      spectrometry (LDPI-MS) was developed to investigate the competence and
      sporulation factor-a pentapeptide of amino acid sequence ERGMT-within intact
      Bacillus subtilis biofilms. Derivatization of the neat ERGMT peptide with
      quinoline- and anthracene-based tags was separately used to lower the peptide
      ionization potential and permit direct ionization by 7.87-eV vacuum ultraviolet
      radiation. The techniques of mass shifting and selective ionization of the
      derivatized peptide were combined here to permit detection of ERGMT peptide
      within intact biofilms by LDPI-MS, without any prior extraction or
      chromatographic separation. Finally, imaging MS specific to the derivatized
      peptide was demonstrated on an intact biofilm using LDPI-MS. The presence of
      ERGMT in the biofilms was verified by bulk extraction/LC-MS. However, MALDI
      imaging MS analyses were unable to detect ERGMT within intact biofilms.

PMID- 17222016
TI  - Atmospheric pressure molecular imaging by infrared MALDI mass spectrometry.
AB  - An atmospheric pressure (AP) MALDI imaging interface was developed for an
      orthogonal acceleration time-of-flight mass spectrometer and utilized to analyze
      peptides, carbohydrates, and other small biomolecules using infrared laser
      excitation. In molecular imaging experiments, the spatial distribution of mock
      peptide patterns was recovered with a detection limit of approximately 1
      fmol/pixel from a variety of MALDI matrixes. With the use of oversampling for the
      image acquisition, a spatial resolution of 40 microm, 5 times smaller than the
      laser spot size, was achieved. This approach, however, required that the analyte
      was largely removed at the point of analysis before the next point was
      interrogated. Native water in plant tissue was demonstrated to be an efficient
      natural matrix for AP infrared laser desorption ionization. In soft fruit tissues
      from bananas, grapes, and strawberries, potassiated ions of the most abundant
      metabolites, small carbohydrates, and their clusters produced the strongest peaks
      in the spectra. Molecular imaging of a strawberry skin sample revealed the
      distribution of the sucrose, glucose/fructose, and citric acid species around the
      embedded seeds. Infrared AP MALDI mass spectrometric imaging without the addition
      of an artificial matrix enables the in vivo investigation of small biomolecules
      and biological processes (e.g., metabolomics) in their natural environment.

PMID- 17222015
TI  - Assessing the peak capacity of IMS-IMS separations of tryptic peptide ions in He
      at 300 K.
AB  - Two-dimensional ion mobility spectrometry (IMS-IMS) coupled with mass
      spectrometry is examined as a means of separating mixtures of tryptic peptides
      (from myoglobin and hemoglobin). In this study, we utilize two distinct drift
      regions that are identical in that each contains He buffer gas at 300 K. The two
      dimensional advantage is realized by changing the structures of the ions. As ions
      arrive at the end of the first drift region, those of a specified mobility are
      selected, exposed to energizing collisions, and then introduced into a second
      drift region. Upon collisional activation, some ions undergo structural
      transitions, leading to substantial changes in their mobilities; others undergo
      only slight (or no) mobility changes. Examination of peak positions and shapes
      for peptides that are separated in the first IMS dimension indicates experimental
      peak capacities ranging from approximately 60 to 80; the peak shapes and range of
      changes in mobility that are observed in the second drift region (after
      activation) indicate a capacity enhancement ranging from a factor of
      approximately 7 to 17. Thus, experimental (and theoretical) evaluation of the
      peak capacity of IMS-IMS operated in this fashion indicates that capacities of
      approximately 480 to 1360 are accessible for peptides. Molecular modeling
      techniques are used to simulate the range of structural changes that would be
      expected for tryptic peptide ions and are consistent with the experimental shifts
      that are observed.

PMID- 17222017
TI  - Macroporous ultramicroelectrodes for improved electroanalytical measurements.
AB  - Recent work on the preparation of highly organized macroporous electrodes and
      nanoporous ultramicroelectrodes has been combined and extended to elaborate
      macroporous ultramicroelectrodes (UMEs) by template synthesis using colloidal
      crystals and following two different and complementary methods. On the one hand,
      arched porous UMEs were prepared, and on the other hand, cylindrical porous UMEs
      were obtained by using cavity UMEs. These macroporous UMEs have an active surface
      area which is up to 2 orders of magnitude higher compared to that of a classical
      disk UME as characterized by cyclic voltammetry. To study their analytical
      performance, the macroporous UMEs have been modified with a redox-active thiol
      and also a model bioelectrocatalytical system containing a redox mediator, a
      cofactor, and glucose-dehydrogenase. In both cases the electrochemical signal is
      amplified by up to 2 orders of magnitude, which increases significantly the
      analytical performance of such electrodes and therefore opens up new applications
      for this kind of miniaturized electrochemical system.

PMID- 17222018
TI  - MicroSPE-nanoLC-ESI-MS/MS using 10-microm-i.d. silica-based monolithic columns
      for proteomics.
AB  - Silica-based monolithic capillary columns (25 cm x 10 microm i.d.) with
      integrated nanoESI emitters have been developed to provide high-quality and
      robust microSPE-nanoLC-ESI-MS analyses. The integrated nanoESI emitter adds no
      dead volume to the LC separation, allowing stable electrospray operation at flow
      rates of approximately 10 nL/min. In an initial application with a linear ion
      trap MS, we identified 5510 unique peptides that covered 1443 distinct Shewanella
      oneidensis proteins from a 300-ng tryptic digest sample in a single 4-h LC-MS/MS
      analysis. The use of an integrated monolithic ESI emitter provided enhanced
      resistance to clogging and provided good run-to-run reproducibility.

PMID- 17222019
TI  - Oriented immobilization of antibodies with GST-fused multiple Fc-specific B
      domains on a gold surface.
AB  - We have constructed a novel platform for the oriented buildup of immunoglobulins
      on a gold surface for a surface plasmon resonance imaging microarray. To this
      end, genetically engineered glutathione S-transferase proteins bearing one, two,
      and three Fc-specific B-domains in protein G from Streptococci (GST-GB1, -GB2,
      and -GB3, respectively) were produced. In order to tether these GST-GBx proteins
      specifically, a novel glutathione-derivatized ligand (LA-GSH) was also
      synthesized from a biaminated tri(ethylene glycol) backbone. Each end of the
      backbone was further functionalized with a maleimide group for a glutathione
      modification and a lipoic acid for surface immobilization. The glutathione ligand
      demonstrated a negligible nonspecific protein adsorption toward other spectator
      proteins while showing a strong specific association toward GST-GBx proteins.
      This Fc-specific surface exhibited at least a 2-fold enhancement in the
      immunoglobulin density (from human and mouse) with its antigen capture capability
      totally conserved compared to a covalently tethered GBx proteins. A single
      antibody tethered on the GST-GB3 is estimated to capture two antigens (enhanced
      green fluorescent protein), and this antigen capture ratio seems to be the most
      efficient value ever observed.

PMID- 17222020
TI  - Raman spectroscopic characterization of porcine brain tissue using a single fiber
      optic probe.
AB  - Accurate targeting of diseased and healthy tissue has significantly been improved
      by MRI/CT-based navigation systems. Recently, intraoperative MRI navigation
      systems have proven to be powerful tools for the guidance of the neurosurgical
      operations. However, the widespread use of such systems is held back by the
      costs, the time consumption during operation, and the need for MR-compatible
      surgical devices. Raman spectroscopy is a nondestructive optical technique that
      enables real-time tissue identification and classification and has proved to be a
      powerful diagnostic tool in a large number of studies. In the present report, we
      have investigated the possibility of distinguishing different brain structures by
      using a single fiber-optic probe to collect Raman scattered light in the high
      wavenumber region of the spectrum. For the Raman measurements, 7 pig brains were
      sliced in the coronal plain and Raman spectra were obtained of 11-19 anatomical
      structures. Adjacent brain structures could be distinguished based on their Raman
      spectra, reflecting the differences in their biochemical composition and
      illustrating the potential Raman spectroscopy holds as a guidance tool during
      neurosurgical procedures.

PMID- 17222021
TI  - Gradient elution moving boundary electrophoresis for high-throughput multiplexed
      microfluidic devices.
AB  - A novel method for performing electrophoretic separations is described-gradient
      elution moving boundary electrophoresis (GEMBE). The technique utilizes the
      electrophoretic migration of chemical species in combination with variable
      hydrodynamic bulk counterflow of the solution through a separation capillary or
      microfluidic channel. Continuous sample introduction is used, eliminating the
      need for a sample injection mechanism. Only analytes with an electrophoretic
      velocity greater than the counterflow velocity enter the separation channel. The
      counterflow velocity is varied over time so that each analyte is brought into the
      separation column at different times, allowing for high-resolution separations in
      very short channels. The new variable of bulk flow acceleration affords a new
      selectivity parameter to electrophoresis analogous to gradient elution
      compositions in chromatography. Because it does not require extra channels or
      access ports to form an injection zone and because separations can be performed
      in very short channels, GEMBE separations can be implemented in much smaller
      areas on a micro-fluidic chip as compared to conventional capillary
      electrophoresis. Demonstrations of GEMBE separations of small dye molecules,
      amino acids, DNA, and immunoassay products are presented. A low-cost, polymeric,
      eight-channel multiplexed microfluidic device was fabricated to demonstrate the
      reduced area requirements of GEMBE; the device was less than 1 in.2 in area and
      required only n + 1 fluidic access ports per n analyses (in this instance, nine
      ports for eight analyses). Parallel separations of fluorescein and
      carboxyfluorescein yielded less than 3% relative standard deviation (RSD) in
      interchannel migration times and less than 5% RSD in both peak and height
      measurements. The device was also used to generate a calibration curve for a
      homogeneous insulin immunoassay using each of the eight channels as a calibration
      point with less than 5% RSD at each point with replicate analyses.

PMID- 17222022
TI  - Multiplex biosensor using gold nanorods.
AB  - Gold nanorods (GNRs) with different aspect ratios were fabricated through seed
      mediated growth and surface activation by alkanethiols for the attachment of
      antibodies to yield gold nanorod molecular probes (GNrMPs). Multiplex sensing was
      demonstrated by the distinct response of the plasmon spectra of the GNrMPs to
      binding events of three targets (goat anti-human IgG1 Fab, rabbit anti-mouse IgG1
      Fab, rabbit anti-sheep IgG (H+L)). Plasmonic sensors are highly specific and
      sensitive and can be used to monitor refractive index changes caused by molecular
      interactions in their immediate vicinity with potential to achieve single
      particle biosensing. This technique can play a key role in developing novel
      optical biosensors for both in vivo and in vitro detection and single-receptor
      kinetics.

PMID- 17222023
TI  - Determination of the magneto-optical relaxation of magnetic nanoparticles as a
      homogeneous immunoassay.
AB  - The interaction between human eotaxin (hEotaxin) and its polyclonal antibody anti
      human eotaxin (anti-hEotaxin) was investigated by means of a novel liquid-phase
      immunoassay using the magneto-optical relaxation of ferrofluids. The binding
      quality as well as kinetic properties of the binding partners was determined
      using specifically binding magnetic probes. For this purpose, magnetic
      nanoparticles (MNP; DDM128N, Meito Sangyo, Japan) were initially functionalized
      with streptavidin. The biotin-nylated antibody was conjugated with streptavidin
      MNP applying the streptavidin-biotin binding system. Binding reactions were
      detected by measuring the relaxation of the optical birefringence signal
      occurring when a pulsed magnetic field is applied to the ferrofluid. The addition
      of hEotaxin to anti-hEotaxin conjugated MNP in different amounts yielded an
      enlargement of the mean relaxation time due to the formation of MNP aggregates.
      In order to express the observed increase of the particles' effective diameter in
      terms of elementary kinetic processes between antigen and antibody, a kinetic
      model was introduced. Here, the binding reactions are described by a process of
      stepwise polymerization. The obtained results were compared with data received
      from surface plasmon resonance biosensor analysis, a standard tool for
      biomolecular interaction analysis.

PMID- 17222024
TI  - Determination of phenolic metabolites of polycyclic aromatic hydrocarbons in
      human urine as their pentafluorobenzyl ether derivatives using liquid
      chromatography-tandem mass spectrometry.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental
      contaminants, and a number of them are carcinogenic. One approach for measuring
      exposure to them is to determine the concentrations of metabolites in urine. The
      pyrene metabolite 1-hydroxypyrene has been used as a biomarker for exposure in
      numerous studies. However, determination of exposure to several PAHs may be
      advantageous, since the relative amounts may vary depending upon the exposure
      source. We developed a liquid chromatography-tandem mass spectrometry method for
      the determination of phenolic metabolites of naphthalene, fluorene, phenanthrene,
      and pyrene in human urine. Following enzymatic cleavage of the glucuronide and
      sulfate conjugates, the phenolic metabolites are extracted from urine and
      converted to pentafluorobenzyl ethers. These derivatives greatly enhance the
      sensitivity of detection by atmospheric pressure chemical ionization in the
      negative ion mode. Lower limits of quantitation range from 0.01 to 0.5 ng/mL.
      Stable isotope-labeled internal standards were synthesized or obtained
      commercially. Data on urinary excretion of several PAH metabolites in urine of
      smokers and nonsmokers are presented.

PMID- 17222025
TI  - Triple oxygen isotope analysis of nitrate using the denitrifier method and
      thermal decomposition of N2O.
AB  - Interaction with ozone transfers its anomalous (non-mass-dependent) 17O
      enrichment to atmospheric nitrogen oxides and nitrate. The 17O anomaly (Delta17O)
      in nitrate can be used to identify atmospheric nitrate inputs into terrestrial
      and aquatic environments as well as to study the role of ozone in the
      atmosphere's reactive nitrogen cycle. We report here on an online method for
      analysis of the 17O anomaly, using a strain of denitrifiers to convert nitrate to
      N2O, which decomposes quantitatively to N2 and O2 in a gold furnace at 800
      degrees C, followed by gas chromatographic separation and isotope analysis of O2.
      This method requires approximately 50 nmol of nitrate, 2-3 orders of magnitude
      less than previous offline thermal decomposition methods to achieve a similar
      analytical precision of 0.5 per thousand for Delta17O. There is no significant
      memory effect, but calibration via nitrate or N2O reference materials is required
      for scale normalization. The N2O decomposition method is shown to be well-suited
      for nitrate analysis in freshwater and seawater samples from various
      environments.

PMID- 17222026
TI  - Application of raman spectroscopy and sequential injection analysis for pH
      measurements with water dispersion of polyaniline nanoparticles.
AB  - A novel method for pH measurements between pH 7.5 and 10.4 is reported in this
      paper. The method combines Raman spectroscopy and the automated sequential
      injection analysis system (SIA) and makes use of the acid-base properties of a
      commercially available water dispersion of polyaniline (PANI) nanoparticles with
      a mean particle size of 46 nm. The useful pH range of the PANI nanoparticles is
      broader than for conventional acid-base indicators, due to the 1:2 reaction
      stoichiometry of the proton-ligand complex of the nanoparticles. The pH
      measurements were conducted with the 633-nm laser excitation wavelength by
      calculating the difference between the Raman intensities of the primary and
      reference wavenumbers. In this study, the pH-sensitive CH=CH stretching band at
      1422 cm-1 and C-H in-plane bending band of the quinoid form at 1163 cm-1 were
      chosen as the primary wavenumbers. The presented method is fast and allows pH to
      be measured with a precision of 0.2 pH unit. The advantage of the proposed method
      is that the hysteresis effect, which is usually observed for PANI films, can be
      overcome with the PANI nanoparticles, because a fresh nanoparticle solution is
      used in each measurement. It should be pointed out, that this work is a
      fundamental study showing the applicability of Raman spectroscopy in combination
      with the SIA technique for pH measurements in specific applications, where the
      conventional glass pH electrode cannot be used.

PMID- 17222027
TI  - Quantitative measurement of cardiac markers in undiluted serum.
AB  - Two mycocardial infarction biomarkers, myoglobin (MG) and cardiac troponin I
      (cTnI), were quantified at biological levels and in undiluted serum without
      sample pretreatment using surface plasmon resonance (SPR) sensors. To achieve
      detection of biomarkers in undiluted serum (72 mg/mL total protein
      concentration), minimization of the nonspecific signal from the serum protein was
      achieved by immobilizing the antibody for the biomarkers on an N
      hydroxysuccinimide activated 16-mercaptohexadecanoic acid self-assembled
      monolayer. This monolayer reduces the nonspecific signal from serum proteins in
      such a manner that short exposure of the sensor to serum prior to analysis
      prevents any further nonspecific adsorption during analysis. Thus, sensing of MG
      and cTnI was achieved on the basis of the difference between signals from the
      active sensor and a reference sensor that captured background interference. This
      resulted in direct measurement of these biomarkers in undiluted serum. Detection
      limits for both markers were below 1 ng/mL, which is below the threshold needed
      to detect myocardial infarction. Detecting biomarkers in the low ng/mL range
      without signal amplification in such a complex matrix as serum corresponds to a
      selectivity of 108. The root-mean-square-error (RMSE) of calibration was below 2
      ng/mL.

PMID- 17222028
TI  - Direct extraction of double-stranded DNA into ionic liquid 1-butyl-3
      methylimidazolium hexafluorophosphate and its quantification.
AB  - Ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6), as a
      green solvent, was successfully used for the direct extraction of dsDNA. The
      extraction efficiency and the distribution coefficient values indicated that
      trace amounts of DNA at the levels of <5 ng microL-1 facilitate quantitative fast
      extraction, while proteins and metal species do not interfere. A total of 30% of
      the DNA in ionic liquid at approximately 20 ng microL-1 was back extracted into
      aqueous phase in phosphate-citrate buffer with a single-stage extraction. The
      extraction is demonstrated to be endothermic with an enthalpy of 34.3 kJ moL-1.
      The extraction mechanisms were proposed and verified by 31P NMR and FT-IR
      spectra. Interactions between cationic 1-butyl-3-methylimidazolium (Bmim+) and P
      O bonds of phosphate groups in the DNA strands take place both in the dissolved
      BmimPF6 in aqueous phase and at the interface of the two phases. This interaction
      consequently led to the transformation of DNA conformations, along with a
      reduction of ethidium resonance light scattering at 510 nm, and a procedure for
      DNA quantification in ionic liquid was developed based on this observation.

PMID- 17222029
TI  - Voltammetric monitoring of transient hydrodynamic flow profiles in microfluidic
      flow cells.
AB  - We consider the transition to steady-state flow in the inlet region of a
      hydrodynamic channel cell and show that a microelectrode positioned within this
      inlet region allows chronoamperometric results to be recorded, from which
      information about the extent of the development of the flow profile may be
      deduced as well as information about the precise dimensions of the microfluidic
      channel.

PMID- 17222030
TI  - Backside calibration potentiometry: ion activity measurements with selective
      supported liquid membranes by calibrating from the inner side of the membrane.
AB  - In direct potentiometry, the magnitude of the measured potentials is used to
      determine the composition of the sample. While this places rather formidable
      demands on the required reproducibility of the associated potential measurements,
      typically on the order of microvolts, in vitro clinical analyses of blood samples
      are today successfully performed with direct potentiometry using ion-selective
      electrodes (ISEs). Unfortunately, most other analytical situations do not permit
      the sensor to be recalibrated every few minutes, as in environmental monitoring
      or in vivo measurements, and direct potentiometry is often bound to fail as an
      accurate method in these circumstances. This paper introduces a novel direction
      for potentiometric sensing, termed backside calibration potentiometry. Chemical
      asymmetries across thin supported liquid ISE membranes are assessed by
      determining the direction of potential drift upon changing the stirring rate on
      either side of the membrane. Disappearance of this drift indicates the
      disappearance of concentration gradients across the membrane and is used to
      determine the sample composition if the solution composition at the backside of
      the membrane and the interfering ion concentration in the sample are known. For
      practical determinations, the concentration of either the primary or the
      interfering ion is varied in the reference solution until the stirring effect
      disappears. The procedure is demonstrated with a Ca2+-selective membrane using
      Ba2+ as the dominant interfering ion. Another example includes the determination
      of Pb2+ in environmental samples where the pH is adjusted to a known level. At pH
      4.0, H+ turns out to be the dominant interfering ion. The practical applicability
      of the method is shown with different environmental water samples, for which the
      results obtained with the novel method are compared with those obtained by
      traditional calibration using standard additions. The limitations of the novel
      method in terms of accuracy and applicable concentration ranges are discussed.

PMID- 17222031
TI  - Preparation and evaluation of a molecularly imprinted polymer derivatized silica
      monolithic column for capillary electrochromatography and capillary liquid
      chromatography.
AB  - A method for preparation of molecularly imprinted polymer (MIP) derivatized onto
      the surface of a monolithic silica capillary column was successfully developed.
      The vinyl groups were first introduced onto the silica monolith by immobilization
      of gamma-methacryloxypropyltrimethoxysilane. Then the MIP coating was
      copolymerized and anchored onto the surface of the silica monolith. Acetonitrile
      was selected as porogen (solvent). The other preparation conditions, such as
      monomer concentration, temperature, and time of polymerization, were
      systematically studied. The obtained MIP-derivatized silica monolith using l
      tetrahydropalmatine (l-THP) and (5S,11S)-(-)-Troger's base (S-TB) as the
      imprinted template, respectively, was characterized in terms of the retention
      behavior of thiourea and toluene. Under the optimized CEC conditions, baseline
      enantioseparations of THP and TB were achieved in 4 min though the effective
      length of the columns was 8.5 cm. The result indicates that enough recognition
      sites were on the surface of silica monolith, resulting in strong recognition
      ability. Compared with a MIP organic monolith, the MIP-derivatized silica
      monolith exhibits better column efficiency and stability in CEC. Additionally,
      the comparison of these two kinds of monolithic columns was performed by
      capillary liquid chromatography. The separation on MIP-derivatized silica
      monolith was superior to that on the organic monolith.

PMID- 17222032
TI  - Glycerin suppression of fluorescence self-quenching and improvement of
      heterogeneous fluoroimmunoassay sensitivity.
AB  - Fluorescent labels find wide application in immunoassays and immunosensors as
      well as in protein and DNA chips. However, the use of fluorescent labels in
      applications requiring high detection sensitivity is limited by fluorescence self
      quenching observed when a relatively high number of fluorescent compounds is
      introduced in the recognition molecule. Here we describe a simple method that
      suppresses effectively fluorescence self-quenching observed when highly labeled
      antibodies are used as labels in immunoassays. This was achieved by treating the
      microtitration wells after the completion of the immunoassay with a glycerin
      solution followed by 15-min incubation of the emptied wells at 37 degrees C. The
      remedial action of this method on self-quenching was studied through a
      noncompetitive immunofluorometric assay for rabbit gamma-globulins employing a
      sheep anti-rabbit gamma-globulin antibody labeled with fluorescein at molar
      ratios ranging from 1.0 to 17.4. The glycerin/thermal treatment increased the
      fluorescence signal measured directly onto the solid surface by 9.2-117% for the
      antibodies with molar ratios of 1.0-17.4, compared with the values obtained prior
      to treatment. Furthermore, fluorescence self-quenching was completely removed for
      labeling ratios up to 14.0. The assay sensitivity was improved 2-4 times by the
      glycerin/thermal treatment when heavily fluoresceinated antibodies are used as
      labels (molar ratio >/=5.6). The proposed method resulted also in increased
      fluorescence signals when labels other than fluorescein were used and improved
      considerably the detection of protein spots on silicon dies.

PMID- 17222033
TI  - Analysis of a model virus using residue-specific chemical cleavage and MALDI-TOF
      mass spectrometry.
AB  - A nonenzymatic proteomics strategy is applied to the rapid identification of
      viruses. The approach provides solubilization and subsequent digestion of viral
      coat proteins in under 30 s. Acid digestions were carried out using a laboratory
      quality microwave system equipped with temperature, pressure, and power controls,
      which allowed for precise optimization of experimental parameters. Under optimal
      conditions, this method provides an efficient alternative to traditional
      enzymatic digestion-based methods for virus identification. Following rapid
      microwave heating of a suspension of a model virus, RNA bacteriophage MS2, 13
      chemical digestion products were detected in parallel with the coat protein
      precursor using MALDI-TOF MS. Because of the high sequence coverage obtained, the
      bacteriophage MS2 coat protein was identified with high confidence and the
      specificity of the identification allowed for the discrimination between
      bacteriophage MS2 and other closely related RNA bacteriophages.

PMID- 17222034
TI  - Detection of functional ricin by immunoaffinity and liquid chromatography-tandem
      mass spectrometry.
AB  - The toxin ricin is a biological weapon that may be used for bioterrorist
      purposes. As a member of the group of ribosome-inactivating proteins (RIPs),
      ricin has an A-chain possessing N-glycosidase activity which irreversibly
      inhibits protein synthesis. In this paper, we demonstrate that provided
      appropriate sample preparation is used, this enzymatic activity can be exploited
      for functional ricin detection with sensitivity similar to the best ELISA and
      specificity allowing application to environmental samples. Ricin is first
      captured by a monoclonal antibody directed against the B chain and immobilized on
      magnetic beads. Detection is then realized by determination of the adenine
      released by the A chain from an RNA template using liquid chromatography coupled
      to tandem mass spectrometry. The immunoaffinity step combined with the enzymatic
      activity detection leads to a specific assay for the entire functional ricin with
      a lower limit of detection of 0.1 ng/mL (1.56 pM) after concentration of the
      toxin from a 500 microL sample size. The variability of the assay was 10%.
      Finally, the method was applied successfully to milk and tap or bottled water
      samples.

PMID- 17222035
TI  - Specific postcolumn detection method for HPLC assay of homocysteine based on
      aggregation of fluorosurfactant-capped gold nanoparticles.
AB  - Gold nanoparticles (GNPs) capped with nonionic fluorosurfactant molecules (Zonyl
      FSN) were synthesized, and with the colloidal solution as a probe reagent, a new
      postcolumn colorimetric detection method for HPLC assay of homocysteine (Hcy) has
      been developed. The FSN-capped GNPs exhibited excellent stability in aqueous
      solutions, even in the presence of high salt. The aggregation of the GNPs could
      be induced by either Hcy or cysteine, resulting in an absorption decrease of the
      colloidal solution at 525 nm and an absorption increase at longer wavelengths
      (600-700 nm); however, the GNPs did not respond to other amino acids and
      biomolecules such as glutathione, cysteinylglycine, and glucose. Under optimal
      conditions (i.e., high salt, neutral pH, and approximately 70 degrees C), the
      color change of the GNP solution could almost complete ( approximately 90%)
      within approximately 30 s upon the addition of Hcy. The high selectivity and very
      fast kinetics of the reaction make it a promising system for HPLC postcolumn
      detection. The new technique has been employed to determine total Hcy levels in
      human urine and plasma samples, and the results are satisfactory.

PMID- 17222037
TI  - Micropallet arrays for the separation of single, adherent cells.
AB  - The selection and collection of single cells from within a heterogeneous
      population is required to produce genetically engineered cell lines, to develop
      new stem cell lines, and for single-cell studies. We describe a new platform for
      the positive selection of single live mammalian cells while the cells remain
      adherent to their growth surface. Cells were grown on arrays of microfabricated,
      releasable elements composed of SU-8 polymer termed "cell pallets". The presence
      of air between the elements restricted the cells to the top surfaces of the
      pallets. Single pallets situated within large arrays of pallets were released on
      demand using a single, focused, laser pulse. The laser pulses were low in energy
      (2-5 muJ) and did not detach nearby, nontargeted pallets. Since the SU-8 pallets
      and the underlying glass substrate were optically transparent, the cells on the
      pallets could be visualized by microscopy before and after release. Over 90% of
      cells remained attached to the pallet during laser-based release. The feasibility
      of growing the cells from the released pallets into clonal colonies was
      demonstrated. The pallet array system permits adherent cells to be inspected
      using conventional microscopy and selected cells released for further analysis.
      The ability to assess cells while they remain adherent to a surface will broaden
      the number of attributes that can be utilized for cell separation, for example,
      cell shape, cytoskeletal properties, and other attributes.

PMID- 17222036
TI  - Methyl esterification assisted MALDI FTMS characterization of the orcokinin
      neuropeptide family.
AB  - Methyl esterification of a peptide converts carboxylic acids, such as those
      present on the side chains of aspartic (D) and glutamic acid (E) as well as the
      free carboxyl terminus, to their corresponding methyl esters. This method has
      been applied to peptide and protein quantitation, de novo sequencing, and
      reduction of nonspecific binding in immobilized metal affinity chromatography for
      enrichment of phosphorylated peptides. In this study, we investigate the
      application of this derivatization reaction to the identification and
      characterization of the orcokinin neuropeptide family by screening and localizing
      the acidic side chains in peptides. The methyl esterification reaction
      drastically improves the fragmentation efficiency of modified orcokinins due to
      blockage of the aspartate selective cleavage pathway of the native orcokinin
      peptides. With the improved sustained off-resonance irradiation-collisional
      induced dissociation spectra, the number and the locations of D and E residues
      are easily deduced. In addition, a side reaction that occurs at the carboxamide
      group of asparagine (N) is studied. The deamidation followed by subsequent methyl
      esterification reaction mechanism is proposed based on the study of an isotope
      labeled standard N*FDEIDR. Reaction kinetics is studied by elevating the
      temperature from room temperature to 37 degrees C. The deamidation-methyl
      esterification products are greatly enhanced with elevated reaction temperature.
      Furthermore, we also explore the utility of this side reaction for rapid
      screening and characterization of C-terminally amidated neuropeptides. This
      derivatization reaction is applied to both in situ direct tissue neuropeptide
      analysis and the analysis of HPLC fractions from the separation of complex
      neuronal tissue extracts. Overall, this study reports a simple and effective
      method for profiling and localizing acidic amino acid residues (D/E), amide
      containing residues (N/Q), and the C-terminal amide group in a peptide.

PMID- 17222038
TI  - Online standard additions calibration of transient signals for inductively
      coupled plasma mass spectrometry.
AB  - An online standard additions calibration method for transient signals in ICPMS is
      demonstrated in which a small volume of standard is injected as a spike into the
      sample/carrier stream, overlaying the analyte peak. This technique provides the
      advantages of conventional standard additions but requires only a single sample
      run. The method corrects for matrix effects and is suitable for transient signals
      in which the severity of the matrix effect changes over the analyte peak. The
      method uses a peak-fitting program to determine the area of the underlying peak
      and is shown to be effective for the determination of trace metal concentrations
      in both a high ionic strength matrix and in a biological matrix (urine). Eight
      analytes with concentrations in the range of 0.82-233.2 mug L-1 in urine were
      simultaneously determined using a standard spiking solution of 75 mug L-1
      injected through a 100-muL loop. The measured concentrations for analytes free of
      spectral interferences agreed with the certified values, and the precision
      achieved was comparable to that achieved by the certifying agency. Using a
      conventional cross-flow nebulizer and Scott-type spray chamber, the accuracy
      obtained for online standard additions calibration was within 2%, and the
      precision was within 5%.

PMID- 17222040
TI  - Differential surface plasmon resonance imaging for high-throughput bioanalyses.
AB  - A new imaging technique for high-throughput surface plasmon resonance (SPR)
      measurements is described. It is the application of a CCD camera for simultaneous
      processing of two images at two different wavelengths provided by two laser
      diodes. The two lasers are brought to resonance by tuning of the angle of
      incidence so that the detection power and the dynamic range are optimized for the
      wavelength pair selected. Applying a special differential processing of the two
      images, SPR measurements can be performed near the shot noise limit taking into
      account the number of CCD pixels involved. It is shown that the detection limit
      of imaging methods can be improved significantly if the working point is set near
      to the reflection minimum instead of choosing the angle with the steepest slope
      of the reflection curve. The technique is demonstrated by simultaneous
      measurement of hybridization reactions of three different types of thiolated
      oligonucleotides in 30 small areas set by a commercial spotter. A noise level of
      1.5 x 10(-6) refractive index units (RIU) was obtained for single, 500 x 500
      microm2 reaction areas. The noise level was about 6 x 10(-7) RIU when five areas
      were taken into account. The present arrangement and the particular spotter
      applied would allow simultaneous measurements of up to 400 binding reactions with
      a noise level of about 1.5 x 10(-6) RIU.

PMID- 17222039
TI  - Direct extraction of penicillin G and derivatives from aqueous samples using a
      stoichiometrically imprinted polymer.
AB  - A molecularly imprinted polymer (MIP) prepared using penicillin G procaine salt
      as the template (PENGp) and a stoichiometric quantity of urea-based functional
      monomer to target the single oxyanionic species in the template molecule has been
      applied to the development of a molecularly imprinted solid-phase extraction
      (MISPE) procedure for the selective preconcentration of beta-lactam antibiotics
      (BLAs) from environmental water samples. Various parameters affecting the
      extraction efficiency of the polymer have been evaluated to achieve the selective
      preconcentration of the antibiotics from aqueous samples and to reduce
      nonspecific interactions. This resulted in an MISPE-HPLC method allowing the
      direct extraction of the analytes from the sample matrix with a selective wash
      using just 10% (v/v) organic solvent. On the basis of UV detection only, the
      method showed good recoveries and precision, ranging between 93% and 100% (RSD
      3.8-8.9%, n = 3) for tap water and between 90% and 100% (RSD 4.2-9.1%, n = 3) for
      river water fortified with 30 or 60 microg L-1 (50 mL samples) penicillin G,
      penicillin V, nafcillin, oxacillin, cloxacillin, and dicloxacillin, suggesting
      that this MIP can be successfully applied to the direct preconcentration of BLAs
      in environmental water samples.

PMID- 17222041
TI  - Selective sample cleanup by reusable sol-gel immunoaffinity columns for
      determination of deoxynivalenol in food and feed samples.
AB  - The paper describes the development of a simple and highly selective method for
      the determination of deoxynivalenol (DON) in food and feed samples. It combines
      sample cleanup with sol-gel immunoaffinity columns containing monoclonal anti-DON
      antibodies and quantification of DON by high-performance liquid chromatography
      with ultraviolet detection. The sol-gel immunoaffinity columns are as selective
      as commercial DON immunoaffinity columns but superior with regard to production
      costs, storage stability, and reusability. In applying the method for the
      analysis of maize, wheat, and spaghetti samples, it offers detection limits (LOD,
      S/N = 3) of 240, 200, and 207 ng/g, and recoveries of 83, 99, and 97%,
      respectively.

PMID- 17222042
TI  - Structure-dependent response of a chemiluminescence nitrogen detector for organic
      compounds with adjacent nitrogen atoms connected by a single bond.
AB  - High-throughput screening (HTS) of chemical libraries is indispensable for drug
      discovery research. However, the HTS data quality for lead discovery, lead
      optimization, and quantitative structure activity relationship studies has been
      severely compromised due to the uncertain compound concentrations in screening
      plates. In order to address this issue, we compared various high-throughput
      technologies for quantification of compounds in microtiter plate format without
      the need for authentic compounds as standards and identified the
      chemiluminescence nitrogen detector (CLND) as the method of choice at the present
      time. However, the structure dependence of this detector has not been well
      studied. A proposed rule suggested that the only exception to equimolar response
      is for compounds that contain adjacent nitrogen atoms. The response should be
      zero when the adjacent nitrogen atoms are connected by a double bond and 0.5 when
      they are connected by a single bond. In this investigation, we studied a broad
      range of compounds with isolated and adjacent nitrogen atoms. We confirmed that
      compounds with isolated nitrogen atoms produce an equimolar response with a 15
      20% variation depending on structures and compounds with adjacent nitrogen atoms
      connected by a double bond giving nearly zero response. We discovered that the
      CLND response for compounds containing adjacent nitrogen atoms that are connected
      with a single bond is highly structure dependent. Substitutions on the nitrogen
      atoms or nearby in the molecule can increase the CLND response to approach a
      value higher than the predicted value 0.5 (maximal value 0.82/nitrogen atom).
      Without substitution, much lower values than predicted (minimal value 0.0
      0.08/nitrogen atom) are obtained. Therefore, the prediction of response of
      0.5/nitrogen atom for compounds with adjacent nitrogen atoms connected by a
      single bond should be abandoned. Compounds with similar structures should be used
      to generate calibration curves for quantification of this class of compounds.

PMID- 17222043
TI  - Identification of natural products using HPLC-SPE combined with CapNMR.
AB  - Two major development areas in HPLC-NMR hyphenation are postcolumn solid-phase
      extraction (HPLC-SPE-NMR) and capillary separations with NMR detection by means
      of solenoidal microcoils (CapNMR). These two techniques were combined off-line
      into HPLC-SPE-CapNMR, which combines the advantage of high loadability of normal
      bore HPLC columns with high mass sensitivity of capillary NMR probes with an
      active volume of 1.5 microL. The technique was used for rapid identification of
      complex sesquiterpene lactones and esterified phenylpropanoids present in an
      essentially crude plant extract (toluene fraction of an ethanolic extract of
      Thapsia garganica fruits). Elution profiles of 10 x 1 mm i.d. SPE cartridges
      filled with poly(divinylbenzene) resin were found to be only marginally broader
      than those observed upon direct injection of 6-microL samples into the probe.
      Thus, the technique focuses analytes emerging in the HPLC elution bands of 0.5-1
      mL into volumes of approximately 10 microL, compatible with the CapNMR probe.
      Using this technique, nine natural products (1-9) present in the plant extract in
      amounts varying from 0.1 to 20% were identified by means of 1D and 2D NMR
      spectra, supported by parallel HPLC-ESIMS measurements. Therefore, HPLC-SPE
      CapNMR should be regarded as an attractive alternative to other applications of
      CapNMR for mixture analysis.

PMID- 17222044
TI  - Enantioseparation and stacking of Cyanobenz[f]isoindole-amino acids by reverse
      polarity capillary electrophoresis and sulfated beta-cyclodextrin.
AB  - A capillary electrophoresis method with laser-induced fluorescence detection for
      the chiral separation of cyanobenz[f]isoindole (CBI) derivatives of amino acids
      was developed and optimized. The enantioseparations are accomplished with
      sulfated beta-CD (S-beta-CD) as chiral selector at low pH and reverse polarity.
      BGE conditions were optimized for CBI-serine and then applied to other CBI-amino
      acids. Baseline resolution of 13 CBI-amino acids was achieved using a single BGE
      formulation of 2 wt % S-beta-CD in 25 mM phosphate buffer at pH 2.00 and a
      voltage of -30 kV. pH is the most critical BGE parameter affecting resolution. At
      2 wt % S-beta-CD, CBI-serine enantiomers are baseline-resolved at pH 2.00 but no
      resolution is obtained at pH 3.00. l-Glutamate, l-aspartate and d-serine are
      simultaneously quantified in the microdialysate of an arctic ground squirrel to
      illustrate the application to biological samples. Dilute solutions of the CBI
      amino acids in water can be stacked by hydrodynamic injection with a 100-fold
      improvement in signal-to-noise ratio without loss of chiral resolution. The
      stacking is proposed to consist of field-amplified migration, pH-mediated
      stacking, and sweeping by S-beta-CD. The limit of detections for CBI-dl-serine
      and CBI-dl-glutamate are determined as 0.20 and 0.30 nM, respectively. The
      stacking method was not applicable to the high ionic strength microdialysates.

PMID- 17222045
TI  - Subsecond detection of physiological adenosine concentrations using fast-scan
      cyclic voltammetry.
AB  - Adenosine modulates blood flow and neurotransmission and may be protective during
      pathological conditions such as ischemia and stroke. A real-time sensor of
      adenosine concentrations is needed to understand its physiological actions and
      the extent of receptor activation. Microelectrodes are advantageous for in vivo
      measurements because they are small and can make fast measurements. The goal of
      this study was to characterize detection of physiological adenosine concentration
      changes at carbon-fiber microelectrodes with subsecond temporal resolution. The
      oxidation potential of adenosine is +1.3 V, so fast-scan cyclic voltammetry
      (FSCV) was performed with an applied potential from -0.4 to 1.5 V and back at 400
      V/s every 100 ms. Two oxidation peaks were detected for adenosine with T-650
      carbon fibers. The second oxidation peak at 1.0 V occurs after the initial
      oxidation at 1.5 V and is due to a sequential oxidation step. Adsorption was
      maximized to obtain detection limits of 15 nM, lower than basal adenosine
      concentrations in the brain. The electrode was insensitive to the metabolite
      inosine and seven times more sensitive to adenosine than ATP. The enzymatic
      degradation of adenosine was monitored with FSCV. This microelectrode sensor will
      be valuable for biological monitoring of adenosine.

PMID- 17222046
TI  - A new competitive fluorescence assay for the detection of patulin toxin.
AB  - Patulin is a toxic secondary metabolite of a number of fungal species belonging
      to the genera Penicillum and Aspergillus. It has been mainly isolated from apples
      and apple products contaminated with the common storage-rot fungus of apples,
      Penicillum expansum, but it has also been extracted from rotten fruits, moldy
      feeds, and stored cheese. Human exposure to patulin can lead to serious health
      problems, and according to a long-term investigation in rats, the World Health
      Organization has set a tolerable weekly intake of 7 ppb body weight. The content
      of patulin in foods has been restricted to 50 ppb in many countries. Conventional
      analytical detection methods involve chromatographic analyses, such as HPLC, GC,
      and, more recently, techniques such as LC/MS and GC/MS. However, extensive
      protocols of sample cleanup are required prior to the analysis, and to accomplish
      it, expensive analytical instrumentation is necessary. An immunochemical
      analytical method, based on highly specific antigen-antibody interactions, would
      be desirable, offering several advantages compared to conventional techniques,
      i.e., low cost per sample, high selectivity, high sensitivity, and high
      throughput. In this paper, the synthesis of two new derivatives of patulin is
      described, along with their conjugation to the bovine serum albumin for the
      production of polyclonal antibodies. Finally, a fluorescence competitive
      immunoassay was developed for the on-line detection of patulin.

PMID- 17222047
TI  - Decolorization of ionic liquids for spectroscopy.
AB  - It has been widely recognized that although ionic liquids should be colorless,
      they are frequently not. Colored samples appear to be pure by most analytical
      techniques (e.g., NMR spectroscopy, mass spectrometry, HPLC, and ion
      chromatography), and there have been many attempts to identify the source of
      color in our own laboratories and others-after 20 years the best that can be said
      is that the impurities are at a very low level (probably parts per billion) with
      very high molar extinction coefficients. In this paper, we do not identify these
      impurities but describe a practical method for removing them for spectrochemical
      applications. We clearly note that the method is not "green", but we anticipate
      that it will only be applied to the small volumes of ionic liquids required for
      fundamental spectroscopic studies in academia but not in industrial processes.

PMID- 17222048
TI  - Instrumentation for medium-throughput two-dimensional capillary electrophoresis
      with laser-induced fluorescence detection.
AB  - In two-dimensional capillary electrophoresis, a sample undergoes separation in
      the first dimension capillary by sieving electrophoresis. Fractions are
      periodically transferred across an interface into a second dimension capillary,
      where components are further resolved by micellar electrokinetic capillary
      electrophoresis. Previous instruments employed one pair of capillaries to analyze
      a single sample. We now report a multiplexed system that allows separation of
      five samples in parallel. Samples are injected into five first-dimension
      capillaries, fractions are transferred across an interface to 5 second-dimension
      capillaries, and analyte is detected by laser-induced fluorescence in a five
      capillary sheath-flow cuvette. The instrument produces detection limits of 940 +/
      350 yoctomoles for 3-(2-furoyl)quinoline-2-carboxaldehyde labeled trypsin
      inhibitor in one-dimensional separation; detection limits degrade by a factor of
      3.8 for two-dimensional separations. Two-dimensional capillary electrophoresis
      expression fingerprints were obtained from homogenates prepared from a lung
      cancer (A549) cell line, on the basis of capillary sieving electrophoresis (CSE)
      and micellar electrophoresis capillary chromatography (MECC). An average of 131
      spots is resolved with signal-to-noise greater than 10. A Gaussian surface was
      fit to a set of 20 spots in each electropherogram. The mean spot width, expressed
      as standard deviation of the Gaussian function, was 2.3 +/- 0.7 transfers in the
      CSE dimension and 0.46 +/- 0.25 s in the MECC dimension. The standard deviation
      in spot position was 1.8 +/- 1.2 transfers in the CSE dimension and 0.88 +/- 0.55
      s in the MECC dimension. Spot capacity was 300.

PMID- 17222049
TI  - Tailoring elution of tetraalkylammonium ions. Ideal electrostatic selectivity
      elution order on a polymeric ion exchanger.
AB  - Although ion exchange is often depicted as a process driven by electrostatic
      forces, ionic solvation or hydrophobic forces contribute greatly to ion exchange
      selectivity and is often the dominant factor. On a variety of commercial anion
      exchange columns, monovalent ClO4- elutes after doubly charged SO42- and even
      triply charged PO43-. For identically charged alkali metal ions, electrostatic
      charge densities based on crystal radii would suggest Li+ to be the most strongly
      retained on a cation exchanger. In practice, it is typically the least strongly
      held cation on most cation exchangers, because of its very high hydration energy
      and with most eluents its capacity factor approaches zero. Even when the ion is
      very poorly solvated, as with tetraalkylammonium (NR4+) cations, there has never
      been a report on a polymeric ion exchanger of an ideal electrostatic selectivity
      order where NR4+ cations elute in their increasing charge density order: R = n
      butyl first, followed by n-propyl, ethyl, and last, methyl. We show that this
      selectivity order is easily achieved on recently described methracrylate-based
      monolithic capillary cation exchange columns (Ueki, Y.; Umemura, T.; Li, J. X.;
      Odake, T; Tsunoda, K. Anal. Chem. 2004, 76, 7007-7012) with minor amounts of
      hydroorganic modifiers. Indeed, under such conditions, Li+ (and other alkali
      cations) elutes after NMe4+.

PMID- 17222050
TI  - Microarray-based kinase inhibition assay by gold nanoparticle probes.
AB  - We report on the development of a new class of kinase microarray for the
      detection of kinase inhibition based on marking peptide
      phosphorylation/biotinylation events by attachment of gold nanoparticles followed
      by silver deposition for signal enhancement. The alpha-catalytic subunit of
      cyclic adenosine 5'-monophosphate-dependent protein kinase (PKA), and its well
      known substrate, kemptide, were used for the purpose of monitoring
      phosphorylation and inhibition. As expected, highly selective inhibition of PKA
      is demonstrated with the four inhibitors: H89, HA1077, mallotoxin, and KN62.
      Furthermore, an inhibition assay demonstrates the ability to detect kinase
      inhibition as well as derive IC50 (half-maximal inhibitory concentration) plots.

PMID- 17222051
TI  - Detection of green fluorescent protein in a single bacterium by capillary
      electrophoresis with laser-induced fluorescence.
AB  - Green fluorescence protein (GFP) is a common reporter used to monitor protein
      expression in single cells. However, autofluorescence from endogenous components
      can mask the signal from GFP, particularly at low expression levels in
      prokaryotes. We employ capillary electrophoresis with laser-induced fluorescence
      for the analysis of the expression of green fluorescent protein in a single
      bacterium. Capillary electrophoresis separates GFP from native cellular
      autofluorescent components, reducing the background signal and improving
      detection limits. Our system provides 100 ymol (60 copies) limits of detection
      for GFP. To demonstrate the performance of this instrument, we employ a model
      system of Deinococcus radiodurans that has been engineered to express GFP under
      the control of the recA promoter. We report resolution and detection of GFP and
      autofluorescent components in a single D. radiodurans bacterium. This paper
      presents the first example of expression of GFP in D. radiodurans and the first
      detection of GFP in a single bacterium by capillary electrophoresis.

PMID- 17222052
TI  - Label-free protein biosensor based on aptamer-modified carbon nanotube field
      effect transistors.
AB  - We have fabricated label-free protein biosensors based on aptamer-modified carbon
      nanotube field-effect transistors (CNT-FETs) for the detection of immunoglobulin
      E (IgE). After the covalent immobilization of 5'-amino-modified 45-mer aptamers
      on the CNT channels, the electrical properties of the CNT-FETs were monitored in
      real time. The introduction of target IgE at various concentrations caused a
      sharp decrease in the source-drain current, and a gradual saturation was observed
      at lower concentrations. The amount of the net source-drain current before and
      after IgE introduction on the aptamer-modified CNT-FETs increased as a function
      of IgE concentration. The detection limit for IgE was determined as 250 pM. We
      have also prepared CNT-FET biosensors using a monoclonal antibody against IgE
      (IgE-mAb). The electrical properties of the aptamer- and antibody-modified CNT
      FETs were compared. The performance of aptamer-modified CNT-FETs provided better
      results than the ones obtained using IgE-mAb-modified CNT-FETs under similar
      conditions. Thus, we suggest that the aptamer-modified CNT-FETs are promising
      candidates for the development of label-free protein biosensors.

PMID- 17222053
TI  - Molecular engineering of dendritic polymers and their application as drug and
      gene delivery systems.
AB  - This review discusses the development of functional and multifunctional
      dendrimeric and hyperbranched polymers, collectively called dendritic polymers,
      with the objective of being applied as drug and gene delivery systems. In
      particular, using as starting materials known and well-characterized basic
      dendritic polymers, the review deals with the type of structural modifications to
      which these dendritic polymers were subjected for the development of drug
      carriers with low toxicity, high encapsulating capacity, a specificity for
      certain biological cells, and the ability to be transported through their
      membranes. Proceeding from functional to multifunctional dendritic polymers, one
      is able to prepare products that fulfill one or more of these requirements, which
      an effective drug carrier should exhibit. A common feature of the dendritic
      polymers is the exhibition of polyvalent interactions, while for multifunctional
      derivatives, a number of targeting ligands determine specificity, another type of
      group secures stability in biological milieu and prolonged circulation, while
      others facilitate their transport through cell membranes. Furthermore, dendritic
      polymers employed for gene delivery should be or become cationic in the
      biological environment for the formation of complexes with the negatively charged
      genetic material.

PMID- 17222054
TI  - Nitric oxide regulates input specificity of long-term depression and context
      dependence of cerebellar learning.
AB  - Recent studies have shown that multiple internal models are acquired in the
      cerebellum and that these can be switched under a given context of behavior. It
      has been proposed that long-term depression (LTD) of parallel fiber (PF)-Purkinje
      cell (PC) synapses forms the cellular basis of cerebellar learning, and that the
      presynaptically synthesized messenger nitric oxide (NO) is a crucial "gatekeeper"
      for LTD. Because NO diffuses freely to neighboring synapses, this volume learning
      is not input-specific and brings into question the biological significance of LTD
      as the basic mechanism for efficient supervised learning. To better characterize
      the role of NO in cerebellar learning, we simulated the sequence of
      electrophysiological and biochemical events in PF-PC LTD by combining established
      simulation models of the electrophysiology, calcium dynamics, and signaling
      pathways of the PC. The results demonstrate that the local NO concentration is
      critical for induction of LTD and for its input specificity. Pre- and
      postsynaptic coincident firing is not sufficient for a PF-PC synapse to undergo
      LTD, and LTD is induced only when a sufficient amount of NO is provided by
      activation of the surrounding PFs. On the other hand, above-adequate levels of
      activity in nearby PFs cause accumulation of NO, which also allows LTD in
      neighboring synapses that were not directly stimulated, ruining input
      specificity. These findings lead us to propose the hypothesis that NO represents
      the relevance of a given context and enables context-dependent selection of
      internal models to be updated. We also predict sparse PF activity in vivo
      because, otherwise, input specificity would be lost.

PMID- 17222055
TI  - Protein and DNA sequence determinants of thermophilic adaptation.
AB  - There have been considerable attempts in the past to relate phenotypic trait-
      habitat temperature of organisms--to their genotypes, most importantly
      compositions of their genomes and proteomes. However, despite accumulation of
      anecdotal evidence, an exact and conclusive relationship between the former and
      the latter has been elusive. We present an exhaustive study of the relationship
      between amino acid composition of proteomes, nucleotide composition of DNA, and
      optimal growth temperature (OGT) of prokaryotes. Based on 204 complete proteomes
      of archaea and bacteria spanning the temperature range from -10 degrees C to 110
      degrees C, we performed an exhaustive enumeration of all possible sets of amino
      acids and found a set of amino acids whose total fraction in a proteome is
      correlated, to a remarkable extent, with the OGT. The universal set is Ile, Val,
      Tyr, Trp, Arg, Glu, Leu (IVYWREL), and the correlation coefficient is as high as
      0.93. We also found that the G + C content in 204 complete genomes does not
      exhibit a significant correlation with OGT (R = -0.10). On the other hand, the
      fraction of A + G in coding DNA is correlated with temperature, to a considerable
      extent, due to codon patterns of IVYWREL amino acids. Further, we found strong
      and independent correlation between OGT and the frequency with which pairs of A
      and G nucleotides appear as nearest neighbors in genome sequences. This
      adaptation is achieved via codon bias. These findings present a direct link
      between principles of proteins structure and stability and evolutionary
      mechanisms of thermophylic adaptation. On the nucleotide level, the analysis
      provides an example of how nature utilizes codon bias for evolutionary adaptation
      to extreme conditions. Together these results provide a complete picture of how
      compositions of proteomes and genomes in prokaryotes adjust to the extreme
      conditions of the environment.

PMID- 17222057
TI  - Delayed goblet cell hyperplasia, acetylcholine receptor expression, and worm
      expulsion in SMC-specific IL-4Ralpha-deficient mice.
AB  - Interleukin 4 receptor alpha (IL-4Ralpha) is essential for effective clearance of
      gastrointestinal nematode infections. Smooth muscle cells are considered to play
      a role in the type 2 immune response-driven expulsion of gastrointestinal
      nematodes. Previous studies have shown in vitro that signal transducer and
      activator of transcription 6 signaling in response to parasitic nematode
      infection significantly increases smooth muscle cell contractility. Inhibition of
      the IL-4Ralpha pathway inhibits this response. How this response manifests itself
      in vivo is unknown. In this study, smooth muscle cell IL-4Ralpha-deficient mice
      (SM-MHC(Cre)IL-4Ralpha(-/lox)) were generated and characterized to uncover any
      role for IL-4/IL-13 in this non-immune cell type in response to Nippostrongylus
      brasiliensis infection. IL-4Ralpha was absent from alpha-actin-positive smooth
      muscle cells, while other cell types showed normal IL-4Ralpha expression, thus
      demonstrating efficient cell-type-specific deletion of the IL-4Ralpha gene. N.
      brasiliensis-infected SM-MHC(Cre)IL-4Ralpha(-/lox) mice showed delayed ability to
      resolve infection with significantly prolonged fecal egg recovery and delayed
      worm expulsion. The delayed expulsion was related to a delayed intestinal goblet
      cell hyperplasia, reduced T helper 2 cytokine production in the mesenteric lymph
      node, and reduced M3 muscarinic receptor expression during infection. Together,
      these results demonstrate that in vivo IL-4Ralpha-responsive smooth muscle cells
      are beneficial for N. brasiliensis expulsion by coordinating T helper 2 cytokine
      responses, goblet hyperplasia, and acetylcholine responsiveness, which drive
      smooth muscle cell contractions.

PMID- 17222056
TI  - Both ligand- and cell-specific parameters control ligand agonism in a kinetic
      model of g protein-coupled receptor signaling.
AB  - G protein-coupled receptors (GPCRs) exist in multiple dynamic states (e.g.,
      ligand-bound, inactive, G protein-coupled) that influence G protein activation
      and ultimately response generation. In quantitative models of GPCR signaling that
      incorporate these varied states, parameter values are often uncharacterized or
      varied over large ranges, making identification of important parameters and
      signaling outcomes difficult to intuit. Here we identify the ligand- and cell
      specific parameters that are important determinants of cell-response behavior in
      a dynamic model of GPCR signaling using parameter variation and sensitivity
      analysis. The character of response (i.e., positive/neutral/inverse agonism) is,
      not surprisingly, significantly influenced by a ligand's ability to bias the
      receptor into an active conformation. We also find that several cell-specific
      parameters, including the ratio of active to inactive receptor species, the rate
      constant for G protein activation, and expression levels of receptors and G
      proteins also dramatically influence agonism. Expressing either receptor or G
      protein in numbers several fold above or below endogenous levels may result in
      system behavior inconsistent with that measured in endogenous systems. Finally,
      small variations in cell-specific parameters identified by sensitivity analysis
      as significant determinants of response behavior are found to change ligand
      induced responses from positive to negative, a phenomenon termed protean agonism.
      Our findings offer an explanation for protean agonism reported in beta2-
      adrenergic and alpha2A-adrenergic receptor systems.

PMID- 17222058
TI  - A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice.
AB  - No single animal model for severe acute respiratory syndrome (SARS) reproduces
      all aspects of the human disease. Young inbred mice support SARS-coronavirus
      (SARS-CoV) replication in the respiratory tract and are available in sufficient
      numbers for statistical evaluation. They are relatively inexpensive and easily
      accessible, but their use in SARS research is limited because they do not develop
      illness following infection. Older (12- to 14-mo-old) BALB/c mice develop
      clinical illness and pneumonitis, but they can be hard to procure, and immune
      senescence complicates pathogenesis studies. We adapted the SARS-CoV (Urbani
      strain) by serial passage in the respiratory tract of young BALB/c mice. Fifteen
      passages resulted in a virus (MA15) that is lethal for mice following intranasal
      inoculation. Lethality is preceded by rapid and high titer viral replication in
      lungs, viremia, and dissemination of virus to extrapulmonary sites accompanied by
      lymphopenia, neutrophilia, and pathological changes in the lungs. Abundant viral
      antigen is extensively distributed in bronchial epithelial cells and alveolar
      pneumocytes, and necrotic cellular debris is present in airways and alveoli, with
      only mild and focal pneumonitis. These observations suggest that mice infected
      with MA15 die from an overwhelming viral infection with extensive, virally
      mediated destruction of pneumocytes and ciliated epithelial cells. The MA15 virus
      has six coding mutations associated with adaptation and increased virulence; when
      introduced into a recombinant SARS-CoV, these mutations result in a highly
      virulent and lethal virus (rMA15), duplicating the phenotype of the biologically
      derived MA15 virus. Intranasal inoculation with MA15 reproduces many aspects of
      disease seen in severe human cases of SARS. The availability of the MA15 virus
      will enhance the use of the mouse model for SARS because infection with MA15
      causes morbidity, mortality, and pulmonary pathology. This virus will be of value
      as a stringent challenge in evaluation of the efficacy of vaccines and
      antivirals.

PMID- 17222059
TI  - Bisphenol A exposure in utero disrupts early oogenesis in the mouse.
AB  - Estrogen plays an essential role in the growth and maturation of the mammalian
      oocyte, and recent studies suggest that it also influences follicle formation in
      the neonatal ovary. In the course of studies designed to assess the effect of the
      estrogenic chemical bisphenol A (BPA) on mammalian oogenesis, we uncovered an
      estrogenic effect at an even earlier stage of oocyte development--at the onset of
      meiosis in the fetal ovary. Pregnant mice were treated with low, environmentally
      relevant doses of BPA during mid-gestation to assess the effect of BPA on the
      developing ovary. Oocytes from exposed female fetuses displayed gross aberrations
      in meiotic prophase, including synaptic defects and increased levels of
      recombination. In the mature female, these aberrations were translated into an
      increase in aneuploid eggs and embryos. Surprisingly, we observed the same
      constellation of meiotic defects in fetal ovaries of mice homozygous for a
      targeted disruption of ERbeta, one of the two known estrogen receptors. This,
      coupled with the finding that BPA exposure elicited no additional effects in
      ERbeta null females, suggests that BPA exerts its effect on the early oocyte by
      interfering with the actions of ERbeta. Together, our results show that BPA can
      influence early meiotic events and, importantly, indicate that the oocyte itself
      may be directly responsive to estrogen during early oogenesis. This raises
      concern that brief exposures during fetal development to substances that mimic or
      antagonize the effects of estrogen may adversely influence oocyte development in
      the exposed female fetus.

PMID- 17222060
TI  - Scrambling eggs in plastic bottles.

PMID- 17222061
TI  - Distinct pigmentary and melanocortin 1 receptor-dependent components of cutaneous
      defense against ultraviolet radiation.
AB  - Genetic variation at the melanocortin 1 receptor (MC1R) is an important risk
      factor for developing ultraviolet (UV) radiation-induced skin cancer, the most
      common form of cancer in humans. The underlying mechanisms by which the MC1R
      defends against UV-induced skin cancer are not known. We used neonatal mouse skin
      (which, like human skin, contains a mixture of melanocytes and keratinocytes) to
      study how pigment cells and Mc1r genotype affect the genome-level response to UV
      radiation. Animals without viable melanocytes (Kit(W-v)/Kit(W-v)) or animals
      lacking a functional Mc1r (Mc1r(e)/Mc1r(e)) were exposed to sunburn-level doses
      of UVB radiation, and the patterns of large-scale gene expression in the basal
      epidermis were compared to each other and to nonmutant animals. Our analysis
      revealed discrete Kit- and Mc1r-dependent UVB transcriptional responses in the
      basal epidermis. The Kit-dependent UVB response was characterized largely by an
      enrichment of oxidative and endoplasmic reticulum stress genes, highlighting a
      distinctive role for pigmented melanocytes in mediating antioxidant defenses
      against genotoxic stresses within the basal epidermal environment. By contrast,
      the Mc1r-dependent UVB response contained an abundance of genes associated with
      regulating the cell cycle and oncogenesis. To test the clinical relevance of
      these observations, we analyzed publicly available data sets for primary melanoma
      and melanoma metastases and found that the set of genes specific for the Mc1r
      dependent UVB response was able to differentiate between different clinical
      subtypes. Our analysis also revealed that the classes of genes induced by UVB
      differ from those repressed by UVB with regard to their biological functions,
      their overall number, and their size. The findings described here offer new
      insights into the transcriptional nature of the UV response in the skin and
      provide a molecular framework for the underlying mechanisms by which melanocytes
      and the Mc1r independently mediate and afford protection against UV radiation.

PMID- 17222064
TI  - [New therapeutic perspectives in iron overload].

PMID- 17222063
TI  - Comparative genomics of large mitochondria in placozoans.
AB  - The first sequenced mitochondrial genome of a placozoan, Trichoplax adhaerens,
      challenged the conventional wisdom that a compact mitochondrial genome is a
      common feature among all animals. Three additional placozoan mitochondrial
      genomes representing highly divergent clades have been sequenced to determine
      whether the large Trichoplax mtDNA is a shared feature among members of the
      phylum Placozoa or a uniquely derived condition. All three mitochondrial genomes
      were found to be very large, 32- to 37-kb, circular molecules, having the typical
      12 respiratory chain genes, 24 tRNAs, rnS, and rnL. They share with the
      Trichoplax mitochondrial genome the absence of atp8, atp9, and all ribosomal
      protein genes, the presence of several cox1 introns, and a large open reading
      frame containing an intron group I LAGLIDADG endonuclease domain. The differences
      in mtDNA size within Placozoa are due to variation in intergenic spacer regions
      and the presence or absence of long open reading frames of unknown function.
      Phylogenetic analyses of the 12 respiratory chain genes support the monophyly of
      Placozoa. The similarities in composition and structure between the three
      mitochondrial genomes reported here and that of Trichoplax's mtDNA suggest that
      their uncompacted state is a shared ancestral feature to other nonmetazoans while
      their gene content is a derived feature shared only among the Metazoa.

PMID- 17222062
TI  - Repeated recruitment of LTR retrotransposons as promoters by the anti-apoptotic
      locus NAIP during mammalian evolution.
AB  - Neuronal apoptosis inhibitory protein (NAIP, also known as BIRC1) is a member of
      the conserved inhibitor of apoptosis protein (IAP) family. Lineage-specific
      rearrangements and expansions of this locus have yielded different copy numbers
      among primates and rodents, with human retaining a single functional copy and
      mouse possessing several copies, depending on the strain. Roles for this gene in
      disease have been documented, but little is known about transcriptional
      regulation of NAIP. We show here that NAIP has multiple promoters sharing no
      similarity between human and rodents. Moreover, we demonstrate that multiple,
      domesticated long terminal repeats (LTRs) of endogenous retroviral elements
      provide NAIP promoter function in human, mouse, and rat. In human, an LTR serves
      as a tissue-specific promoter, active primarily in testis. However, in rodents,
      our evidence indicates that an ancestral LTR common to all rodent genes is the
      major, constitutive promoter for these genes, and that a second LTR found in two
      of the mouse genes is a minor promoter. Thus, independently acquired LTRs have
      assumed regulatory roles for orthologous genes, a remarkable evolutionary
      scenario. We also demonstrate that 5' flanking regions of IAP family genes as a
      group, in both human and mouse are enriched for LTR insertions compared to
      average genes. We propose several potential explanations for these findings,
      including a hypothesis that recruitment of LTRs near NAIP or other IAP genes may
      represent a host-cell adaptation to modulate apoptotic responses.

PMID- 17222065
TI  - [Characterization of the leadership subject areas in the respiratory field in
      Spain].
AB  - OBJECTIVE: The aim of this study was to characterize the leading topics in
      respiratory system in Spain through a bibliometric analysis. MATERIAL AND METHOD:
      For identify and characterize the performance of the different research topics in
      respiratory system in Spain, we compile the production using a journal that turn
      out representative of a broad group of researcher. In this sense the journal
      Archivos de Bronconeumologia is the most important publication in Spanish
      language of this field. RESULTS: A total of 2198 articles published in Archivos
      Bronconeumologia from 1970 to 2000 were analyzed. In each three decades, we did
      not found differences except in the productivity index in oncology in the eighty
      decade and in respiratory failure and sleep disturbance (RFSD) and oncology areas
      in the ninetieth decade and in the Price index (consumption indicators) in the
      diagnostic and therapeutic techniques area in seventy decade. When we compare the
      productivity index of each subject areas between decades, we found a significant
      production increase in the ninetieth decade in asthma, RFSD, tuberculosis, non
      tuberculosis infection, circulation, oncology, pleural disease and interstitial
      areas versus the same in seventy decade, and also, we found significant
      differences between ninetieth and eighty decades in the asthma, RFSD, non
      tuberculosis infection, circulation and pleural disease areas. Tuberculosis area
      maintains an insularity index higher than the other areas. We also found a
      progressive increase in the insularity index of RFSD, non tuberculosis infection,
      oncology and interstitial disease areas. CONCLUSIONS: In general all the
      indicators maintains stable although the more productivity topics were
      respiratory failure and sleep disturbances, and oncology. The productivity has
      increased in asthma, respiratory failure and sleep disturbances, tuberculosis,
      non - tuberculosis respiratory infections, oncology, pulmonary circulation,
      pleura and interstitial disease.

PMID- 17222067
TI  - [Descriptive study of activity of the bone marrow donor registry and bank from
      the Murcia Region (southeast of Spain) (1994-2004)].
AB  - OBJECTIVE: To perform a descriptive study of the activity of the Bank of marrow
      donors from Murcia Region. SUBJECTS AND METHODS: All donors in the Bank of bone
      marrow from 1994 until 2004 (n=3137). This study analysed the number of donors,
      their origin and, performed donor searches activity. Donors were typed by
      serological microlymphocytotoxicity and molecular PCR-SSO and PCR-SSP techniques.
      RESULTS: The Bank of bone marrow has 3,137 voluntary donors typed in low- and
      high-resolution. A total of 680 donor searches have been realized. The origin of
      the donors according to several Areas of Health in which the Autonomous Community
      of Murcia is divided, is the following one: Area I (28%), Area II (18 %), Area
      III (23 %), Area IV (6 %), Area VI (10 %) and other provinces (12%). CONCLUSIONS:
      An increase is observed in the number of annual donors as well as an increase
      very marked of donor searches that are realized every year, especially in 2004.

PMID- 17222066
TI  - [Hospital morbidity in HIV infected patients].
AB  - BACKGROUND AND OBJECTIVE: With the increasing life expectancy in human
      immunodeficiency virus (HIV) infected patients since the highly active
      antiretroviral therapy (HAART), other underlying comorbilities such as chronic
      liver pathology, cardiovascular diseases or side effects of treatment may lead to
      hospitalization. The purpose of this study is to determine the clinical and
      epidemiological characteristics of these patients. MATERIAL AND METHODS: A
      descriptive-retrospective study. We reviewed the clinical records of patients
      with HIV infection admitted in our medical departments through a year. RESULTS:
      There were 125 hospitalizations of 82 patients. 77% were males and 71% had
      hepatitis C virus (HCV) infection. The median age was 42 years. 64% HIV infection
      had been acquired by sharing material for intravenous drug use. A 36% were
      receiving HAART and 51% had AIDS. The respiratory tract pathology (32%) and AIDS
      defining illnesses (22%) were the most frequent causes of hospitalization, and
      the main opportunistic disease was tuberculosis (TBC). Ten per cent were admitted
      in the Intensive Care Unit. Mortality rate was 11% patients/year. CONCLUSIONS:
      Most of the patients were male, drug users and HCV positive, and the admissions
      to hospital were mostly due to respiratory patology and opportunistic diseases.
      TBC remains like the most frequent AIDS-defining illness.

PMID- 17222068
TI  - [Prognostic factors in elderly patients with co-occurring disease in a medium
      long-term and chronic care hospital (MLT&CCH)].

PMID- 17222069
TI  - [Adrenocortical carcinoma. A retrospective analysis of five cases].
AB  - We present five cases of adrenal cortical carcinoma, diagnosed in our hospital
      and we describe the clinical presentation, diagnostic methods and treatment. It
      is a rare tumor, highly aggressive and prognosis is poor. The clinical
      presentation is characterized by a mass effect, symptoms caused by the invasion
      of the structures nearby or by a variety of hormonal changes, especially
      hypercortisolism and virilization. The diagnosis is based on the biochemical
      characterization of the hormonal profile and on imaging techniques, especially
      computed tomography and magnetic resonance. The treatment is generally surgical
      and the most effective chemotherapeutic agents are the adrenolytics (mitotane)
      alone or associated with doxorubicin, cisplatin and etoposide.

PMID- 17222070
TI  - [Pulmonary nocardiosis due to reagudizations in a COPD patient].
AB  - Pulmonary infection due to Nocardia sp. is an infrequent disease that affects
      principally to immunodefficient patients although it can be also seen in patients
      with normal immunity. Diagnosis is based in isolation of micro-organism in
      respiratory samples while clinical presentation and radiology are non specific.
      Treatment is made with trimethropim-sulfametoxazole (TMP/SMX), though resistance
      has developed in some patients. The recommended length of treatment is 6 weeks to
      12 months depending on the immunitaly status. We present the case of a male
      patient of 81 years old affected with COPD and treated with glucocorticoids in a
      chronic basis, who was admitted because relapsing fever episodes during 3 months
      before, weight loss and new hard pulmonary infiltrates with Nocardia sp. cultured
      sputum, and evolution to clinical, radiological and microbiologic resolution with
      TMP/SMX treatment.

PMID- 17222071
TI  - [Rapidly progressive myonecrosis by Aeromonas veronii biotype sobria].
AB  - Myonecrosis due to Aeromonas spp is exceptional. We report the case of a diabetic
      patient with liver cirrhosis who developed a rapidly progressive myonecrosis by
      Aeromonas veronii biotype sobria. The portal of entry was an injury after falling
      down in an irrigation canal. The outcome was not favourable and surgical
      amputation of left leg was performed in spite of antibiotic treatment with
      cefotaxime and tobramicin. Aeromonas spp can be very aggressive and this
      microorganism should be considered in the differential diagnosis of skin and soft
      tissue infections with myonecrosis, specially after posttraumatic wound
      infections with a history of freshwater exposure.

PMID- 17222072
TI  - [Abdominal Burkitt lymphoma in an adolescent].
AB  - We report the case of a male adolescent affected by Burkitt Lymphoma which
      presented as acute abdominal pain and rapid growth mass. It was characterized by
      computed tomography and diagnose was confirmed by bone marrow study. Two
      different chemotherapic regimens were used because of unfavourable evolution, but
      they were not successful. We consider some other causes of abdominal bulky in
      childhood, especially primary tumours and non tumoural diseases.

PMID- 17222073
TI  - [Monoclonal gammopathies differential diagnosis].
AB  - The presence of a monoclonal pike in blood is very habitual in our daily medical
      activity. There are a lot of causes of that. If we know which kind of pathology
      had originated the monoclonal pike, we could be able to bring a suitable
      treatment and to change the prognosis of the patient. If we are able to exclude a
      malignant disease, the patient will not suffer unnecessary aggressive tests. In
      this report, we describe the main diseases which are associated to monoclonal
      pike and the clues to get a definitive diagnosis.

PMID- 17222074
TI  - [Upon scientific accuracy scheme at clinical specialties].
AB  - Will be medical specialties like sciences in the future? Yes, progressively they
      will. Accuracy in clinical specialties will be dissimilar in the future because
      formal-logic mathematics, quantum physics advances and relativity theory
      utilities. Evidence based medicine is now helping to clinical specialties on
      scientific accuracy by the way of decision theory.

PMID- 17222076
TI  - Alternative splicing of pre-messenger RNAs in plants in the genomic era.
AB  - Primary transcripts (precursor-mRNAs) with introns can undergo alternative
      splicing to produce multiple transcripts from a single gene by differential use
      of splice sites, thereby increasing the transcriptome and proteome complexity
      within and between cells and tissues. Alternative splicing in plants is largely
      an unexplored area of gene expression, as this phenomenon used to be considered
      rare. However, recent genome-wide computational analyses have revealed that
      alternative splicing in flowering plants is far more prevalent than previously
      thought. Interestingly, pre-mRNAs of many spliceosomal proteins, especially
      serine/arginine-rich (SR) proteins, are extensively alternatively spliced.
      Furthermore, stresses have a dramatic effect on alternative splicing of pre-mRNAs
      including those that encode many spliceosomal proteins. Although the mechanisms
      that regulate alternative splicing in plants are largely unknown, several reports
      strongly suggest a key role for SR proteins in spliceosome assembly and regulated
      splicing. Recent studies suggest that alternative splicing in plants is an
      important posttranscriptional regulatory mechanism in modulating gene expression
      and eventually plant form and function.

PMID- 17222075
TI  - [Portal and mesenteric vein thrombosis in a patient with a mutation of the 20210
      gen of the prothrombin].

PMID- 17222077
TI  - Rationale and public health implications of changing CHD risk factor definitions.
AB  - The definition of disease is central to the practice of medicine and to public
      health policy. Practice guidelines set standards for disease identification and
      treatment. Quality care is often defined as adherence to these guidelines. Over
      the past few years, the diagnostic thresholds for several common medical
      conditions have been lowered, resulting in a substantial expansion in the market
      for health care. The most recent guidelines for high blood pressure, high
      cholesterol, and impaired fasting glucose each define a high percentage of the
      adult population as in need of regular medical attention. Under the latest
      proposed thresholds, virtually the entire adult population qualifies for a
      chronic condition diagnosis. We evaluate the health and financial outcomes
      associated with changes in diagnostic thresholds for the prevention of three risk
      factors for cardiovascular disease and stroke: blood pressure, serum cholesterol,
      and fasting plasma glucose. Estimates of the numbers of people affected, the cost
      implications, and the overall public health consequences are offered.

PMID- 17222078
TI  - Network analysis in public health: history, methods, and applications.
AB  - Network analysis is an approach to research that is uniquely suited to
      describing, exploring, and understanding structural and relational aspects of
      health. It is both a methodological tool and a theoretical paradigm that allows
      us to pose and answer important ecological questions in public health. In this
      review we trace the history of network analysis, provide a methodological
      overview of network techniques, and discuss where and how network analysis has
      been used in public health. We show how network analysis has its roots in
      mathematics, statistics, sociology, anthropology, psychology, biology, physics,
      and computer science. In public health, network analysis has been used to study
      primarily disease transmission, especially for HIV/AIDS and other sexually
      transmitted diseases; information transmission, particularly for diffusion of
      innovations; the role of social support and social capital; the influence of
      personal and social networks on health behavior; and the interorganizational
      structure of health systems. We conclude with future directions for network
      analysis in public health.

PMID- 17222079
TI  - Seasonality of infectious diseases.
AB  - Seasonality, a periodic surge in disease incidence corresponding to seasons or
      other calendar periods, characterizes many infectious diseases of public health
      importance. The recognition of seasonal patterns in infectious disease occurrence
      dates back at least as far as the Hippocratic era, but mechanisms underlying
      seasonality of person-to-person transmitted diseases are not well understood.
      Improved understanding will enhance understanding of host-pathogen interactions
      and will improve the accuracy of public health surveillance and forecasting
      systems. Insight into seasonal disease patterns may be gained through the use of
      autocorrelation methods or construction of periodograms, while seasonal
      oscillation of infectious diseases can be easily simulated using simple
      transmission models. Models demonstrate that small seasonal changes in host or
      pathogen factors may be sufficient to create large seasonal surges in disease
      incidence, which may be important particularly in the context of global climate
      change. Seasonality represents a rich area for future research.

PMID- 17222080
TI  - Lessons from cost-effectiveness research for United States public health policy.
AB  - The application of cost-effectiveness analysis to health care has been the
      subject of previous reviews. We address the use of economic evaluation methods in
      public health, including case studies of population-level policies, e.g.,
      environmental regulations, injury prevention, tobacco control, folic acid
      fortification, and blood product safety, and the public health promotion of
      clinical preventive services, e.g., newborn screening, cancer screening, and
      childhood immunizations. We review the methods used in cost-effectiveness
      analysis, the implications for cost-effectiveness findings, and the extent to
      which economic studies have influenced policy and program decisions. We discuss
      reasons for the relatively limited impact to date of economic evaluation in
      public health. Finally, we address the vexing question of how to decide which
      interventions are cost effective and worthy of funding. Policy makers have funded
      certain interventions with rather high cost-effectiveness ratios, notably nucleic
      acid testing for blood product safety. Cost-effectiveness estimates are a
      decision aid, not a decision rule.

PMID- 17222081
TI  - Risk communication for public health emergencies.
AB  - This review defines crisis risk communication, traces its origins to a number of
      applied fields, and then shows how basic principles have become incorporated into
      emergency preparedness and risk communication for public health. Literature from
      four different disciplines that inform crisis risk communications are reviewed.
      These are (a) environmental risk communication, (b) disaster management, (c)
      health promotion and communication, and (d) media and communication studies.
      Current curricula and training materials are briefly reviewed. Although this
      literature review suggests much progress has been made to incorporate and
      disseminate crisis risk communication principles into public health practice, and
      case studies suggest that public health workers have gained skills and
      experience, this emerging field still lacks in-depth evaluation of the
      effectiveness of event-specific crisis risk communication efforts.

PMID- 17222082
TI  - A new in vitro wound model based on the co-culture of human dermal microvascular
      endothelial cells and human dermal fibroblasts.
AB  - BACKGROUND INFORMATION: Different in vitro models, based on co-culturing
      techniques, can be used to investigate the behaviour of cell types, which are
      relevant for human wound and soft-tissue healing. Currently, no model exists to
      describe the behaviour of fibroblasts and microvascular endothelial cells under
      wound-specific conditions. In order to develop a suitable in vitro model, we
      characterized co-cultures comprising NHDFs (normal human dermal fibroblasts) and
      HDMECs (human dermal microvascular endothelial cells). The CCSWMA (co-culture
      scratch wound migration assay) developed was supported by direct visualization
      techniques in order to investigate a broad spectrum of cellular parameters, such
      as migration and proliferation activity, the differentiation of NHDFs into MFs
      (myofibroblasts) and the expression of endothelin-1 and ED-A-fibronectin (extra
      domain A fibronectin). The cellular response to hypoxia treatment, as one of the
      crucial conditions in wound healing, was monitored. RESULTS: The comparison of
      the HDMEC-NHDF co-culture with the respective mono-cultures revealed that HDMECs
      showed a lower proliferation activity when co-cultured, but their number was
      stable throughout a period of 48 h. NHDFs in co-culture were slightly slower at
      proliferating than in the mono-culture. The MF population was stable for 48 h in
      the co-culture, as well as in NHDF mono-culture. Co-cultures and HDMEC mono
      cultures were characterized by a slower migration rate than NHDF mono-cultures.
      Hypoxia decreased both cell proliferation and migration in the mono-cultures, as
      well as in the co-cultures, indicating the general suitability of the assay.
      Exclusively, in co-cultures well-defined cell clusters comprising HDMECs and MFs
      formed at the edges of the in vitro wounds. CONCLUSIONS: On the basis of these
      results, the CCSWMA developed using co-cultures, including HDMECs, NHDFs and MFs,
      proved to be an effective tool to directly visualize cellular interaction.
      Therefore, it will serve in the future to evaluate the influence of wound-healing
      related factors in vitro, as shown for hypoxia in the present study.

PMID- 17222083
TI  - Current knowledge of the large RhoGAP family of proteins.
AB  - The Rho GTPases are implicated in almost every fundamental cellular process. They
      act as molecular switches that cycle between an active GTP-bound and an inactive
      GDP-bound state. Their slow intrinsic GTPase activity is greatly enhanced by
      RhoGAPs (Rho GTPase-activating proteins), thus causing their inactivation. To
      date, more than 70 RhoGAPs have been identified in eukaryotes, ranging from yeast
      to human, and based on sequence homology of their RhoGAP domain, we have grouped
      them into subfamilies. In the present Review, we discuss their regulation,
      biological functions and implication in human diseases.

PMID- 17222084
TI  - Why is the microtubule lattice helical?
AB  - Microtubules polymerize from identical tubulin heterodimers, which form a helical
      lattice pattern that is the microtubule. This pattern always has left-handed
      chirality, but it is not known why. But as tubulin, similar to other proteins,
      evolved for a purpose, the question of the title of this artcile appears to be
      meaningful. In a computer simulation that explores the 'counterfactual biology'
      of microtubules without helicity, we demonstrate that these have the same
      mechanical properties as Nature's microtubules with helicity. Thus only a
      dynamical reason for helicity is left as potential explanation. We find that
      helicity solves 'the problem of the blind mason', i.e. how to correctly build a
      structure, guided only by the shape of the bricks. This answer in turn raises
      some new questions for researchers to address.

PMID- 17222086
TI  - Lifesaving decompressive craniectomy in 'malignant' cerebral venous infarction.

PMID- 17222085
TI  - Recommendations for the diagnosis and management of Alzheimer's disease and other
      disorders associated with dementia: EFNS guideline.
AB  - The aim of this international guideline on dementia was to present a peer
      reviewed evidence-based statement for the guidance of practice for clinical
      neurologists, geriatricians, psychiatrists, and other specialist physicians
      responsible for the care of patients with dementia. It covers major aspects of
      diagnostic evaluation and treatment, with particular emphasis on the type of
      patient often referred to the specialist physician. The main focus is Alzheimer's
      disease, but many of the recommendations apply to dementia disorders in general.
      The task force working group considered and classified evidence from original
      research reports, meta-analysis, and systematic reviews, published before January
      2006. The evidence was classified and consensus recommendations graded according
      to the EFNS guidance. Where there was a lack of evidence, but clear consensus,
      good practice points were provided. The recommendations for clinical diagnosis,
      blood tests, neuroimaging, electroencephalography (EEG), cerebrospinal fluid
      (CSF) analysis, genetic testing, tissue biopsy, disclosure of diagnosis,
      treatment of Alzheimer's disease, and counselling and support for caregivers were
      all revised when compared with the previous EFNS guideline. New recommendations
      were added for the treatment of vascular dementia, Parkinson's disease dementia,
      and dementia with Lewy bodies, for monitoring treatment, for treatment of
      behavioural and psychological symptoms in dementia, and for legal issues. The
      specialist physician plays an important role together with primary care
      physicians in the multidisciplinary dementia teams, which have been established
      throughout Europe. This guideline may contribute to the definition of the role of
      the specialist physician in providing dementia health care.

PMID- 17222087
TI  - Pulse-synchronous rotational and vertical pendular eye movements in superior
      canal dehiscence syndrome.

PMID- 17222088
TI  - Pure apraxic agraphia: a disconnection syndrome after left subcortical stroke.

PMID- 17222089
TI  - Dystonic head tremor associated with a parietal lesion.

PMID- 17222090
TI  - Unilateral progressive brain lesions confirmed as multiple sclerosis.

PMID- 17222091
TI  - Ischemic-type posterior inferior cerebellar artery dissection--a case report.

PMID- 17222092
TI  - Extensive neuroimaging of a transient lesion in the splenium of the corpus
      callosum.

PMID- 17222093
TI  - An unusual case of diplopia diagnosed as sarcoidosis on biopsy of testicular
      lump.

PMID- 17222094
TI  - Brain death confirmed with CT angiography.

PMID- 17222096
TI  - Quality of life is not impaired in patients with hereditary neuropathy with
      liability to pressure palsies.

PMID- 17222095
TI  - Repeated syncopes, orthostatic hypotension and progressive visual impairment
      heralding the presentation of an occult gastric adenocarcinoma.

PMID- 17222097
TI  - Hearing loss after cerebrospinal fluid shunt and its resolution following
      programmable valve adjustment.

PMID- 17222098
TI  - A rare case of Toxocara canis cerebral vasculitis.

PMID- 17222105
TI  - The association of post-stroke neurological improvement with risk of subsequent
      deterioration due to stroke events.
AB  - We sought to simultaneously confirm that substantial recovery at day 1 and day 7
      after acute ischaemic stroke onset is associated with subsequent neurological
      deterioration in patients of the Acute Stroke Therapy by Inhibition of
      Neutrophils randomized clinical trial. Substantial recovery was assessed by
      improvement in the National Institutes of Health Stroke Score (NIHSS).
      Neurological deterioration was defined as any stroke event or NIHSS worsening
      from recovery assessment to day 90. After adjusting for age, t-PA and day 1
      NIHSS, there was a non-significant tendency of substantial (pre-specified as 75%)
      recovery at day 1 to be associated with later deterioration [odds ratio (OR)
      2.47; 95% CI, 0.95-6.50]. The corresponding OR for substantial (pre-defined as
      65%) recovery at day 7 was 1.84 (0.85-3.96). Other thresholds for recovery were
      significantly associated with later deterioration: >50%, 80%, 90% and 100% for
      day 1 and >50%, 60%, 70%, 90% and 100% for day 7. The effect of recovery at day 1
      was more important than that of later recovery. This study confirms the
      association between recovery and subsequent neurological deterioration and is the
      first to indicate the greater importance of acute recovery at day 1 in comparison
      with later recovery.

PMID- 17222106
TI  - Screening for SNCA and LRRK2 mutations in Greek sporadic and autosomal dominant
      Parkinson's disease: identification of two novel LRRK2 variants.
AB  - Mutations in SNCA and LRRK2 genes, encoding alpha-synuclein and leucine-rich
      repeat kinase 2, respectively, cause autosomal dominant Parkinson's disease
      (AdPD). The LRRK2 G2019S (c.6055G > A) and R1441G (c.4321C > G) mutations have
      also been identified in sporadic PD (sPD). We studied 55 unrelated patients with
      AdPD, 235 patients with sPD, and 235 healthy age- and gender-matched controls all
      of Greek origin. Patients with AdPD were screened for SNCA and LRRK2 mutations by
      direct sequencing. SNCA gene dosage analysis was also performed for AdPD using
      quantitative duplex polymerase chain reaction of genomic DNA. In addition, we
      investigated the frequency of the LRRK2 G2019S mutation in sPD. We found no
      missense mutations or multiplications in the SNCA gene. Here we report two novel
      variants, A211V (c.632C > T) and K544E (c.1630A > G) in LRRK2 gene in two
      patients with AdPD that was not present in controls. We identified only one
      patient with sPD (1/235; 0.4%) carrying the G2019S mutation. LRRK2 mutations are
      present in AdPD and sPD patients of Greek origin.

PMID- 17222108
TI  - Peripheral large nerve fibre function in patients with chronic plaque psoriasis.
AB  - Accumulating evidence suggests the involvement of neurogenic inflammation in the
      pathogenesis of psoriasis. Moreover, the concomitant occurrence of peripheral
      neuropathy has been reported in several psoriatic patients. Thus, the aim of the
      present study was to answer the question whether an impairment of peripheral
      large nerve fibre function may exist in psoriasis. Thirty-two patients with
      severe and generalized chronic plaque psoriasis and 32 sex- and age-matched
      healthy controls were evaluated by detailed clinical neurological and standard
      neurophysiological examination. The latter included motor nerve conduction study
      of one nerve in the upper and one in the lower extremities and sensory nerve
      conduction study of one nerve in the upper and two in the lower extremities.
      Neurological examination failed to demonstrate any clinical evidence of large
      fibre neuropathy. Furthermore, all values of the examined neurophysiological
      parameters were within normal limits; comparisons of the corresponding mean
      values in the patient and the control group showed no statistically significant
      differences. These findings demonstrate no measurable abnormalities of the
      peripheral large nerve fibres in psoriatic patients and therefore an association
      of psoriasis with peripheral large fibre neuropathy cannot be suggested.

PMID- 17222107
TI  - Serial measurements of plasma homocysteine levels in early and late phases of
      ischemic stroke.
AB  - High plasma levels of homocysteine (Hcy) may predispose to ischemic stroke (IS),
      but results of previous studies have been conflicting. We decided to determine in
      IS patients whether their Hcy levels are elevated, whether levels vary at
      different time points following stroke, whether levels are associated with stroke
      severity, outcome, recurrence, etiology, infarct volume, or risk factors, and
      whether levels are correlated with hemostatic factors or C-reactive protein
      values. We measured plasma Hcy levels in 102 consecutive IS patients on admission
      and at 1 week, 1 month, and 3 months after stroke and once in 102 control
      subjects. Hemostatic factors were measured in 55 patients. Compared with
      controls, plasma Hcy levels in patients were significantly lower on admission but
      not at later time points, with levels increasing by week and remaining at this
      level for 3 months. Hcy levels showed a positive correlation with age and a
      negative correlation with Mini-Mental State Examination (MMSE) scores. Plasma Hcy
      levels inversely correlated with plasminogen activator inhibitor type-1.
      Decreased Hcy levels on admission may reflect the strength of the acute-phase
      response rather than a pathogenetic event. The negative correlation between Hcy
      levels and MMSE scores is more probably age-related than stroke-related.

PMID- 17222109
TI  - Prevention of deep venous thrombosis and pulmonary embolism following stroke: a
      systematic review of published articles.
AB  - We performed a systematic review of the literature on venous thromboembolism
      (VTE) prophylaxis following cerebral infarct (CI) and haemorrhagic stroke.
      MEDLINE, Cochrane, LILACS and SciELO databases were scanned, and the Abstracts
      from Brazilian, American and European Neurology and Stroke Congresses were
      scrutinized for clinical trials. Moreover, the reference lists of articles and
      reviews were searched. A pooled analysis of two large studies with aspirin was
      made. Both unfractionated heparin and low molecular weight heparins/heparinoids
      (LMWH) are partially effective for VTE prophylaxis after CI, and should be
      routinely used in patients with motor deficit and reduced mobility and no
      contraindications. Reduction of deep venous thrombosis is better established than
      the effect over pulmonary embolism or mortality. Some evidence points to a
      greater efficacy of LMWH. The available evidence does not support the use of
      mechanical methods or dextran. Aspirin may have a mild protective effect. Low
      dose Warfarin might be useful in the rehabilitation setting. Strict
      recommendations cannot be made in patients with haemorrhagic stroke but
      intermittent pneumatic compression merits further study. There are important
      limitations of current VTE preventive strategies following stroke. Additional
      studies on the combination of methods after CI and of low doses of anticoagulants
      following cerebral haemorrhage are urgently needed.

PMID- 17222110
TI  - Predictors of long-term neurological sequelae of tuberculous meningitis: a
      multivariate analysis.
AB  - There is paucity of studies on predictors of long-term sequelae of tuberculous
      meningitis (TBM). We report the neurological sequelae of TBM at 1 year and their
      predictors. Patients with TBM who were followed up for 1 year were included. The
      diagnosis of TBM was based on clinical, cerebrospinal fluid (CSF) and computed
      tomography (CT) scan findings. Detailed neurological examinations at admission
      and at 1 year were carried out. All the patients received four-drug
      antitubercular therapy. The frequency of sequelae at 1 year were noted and the
      role of various demographic (age, sex, duration of illness, BCG vaccination),
      clinical (weakness, seizure, extra central nervous system tuberculosis, Glasgow
      Coma Scale (GCS) score, cranial nerve palsy, stage, corticosteroid, drug-induced
      hepatitis, shunt surgery), and laboratory findings (erythrocyte sedimentation
      rate (ESR), CSF cell and protein, CT scan evidences of hydrocephalus, basal
      exudates, infarctions and tuberculoma) at presentation were evaluated employing
      logistic regression analysis. Sixty-five patients with TBM were included in this
      study whose age ranged between 13 and 80 years (mean 33.2), 27 of whom were
      females. Complete neurological recovery at 1 year occurred in 21.5% patients only
      although about 50% were independent for activities of daily living. Neurological
      sequelae were observed in 78.5% patients, which included cognitive impairment in
      55%, motor deficit in 40%, optic atrophy in 37% and other cranial nerve palsy in
      23%. On logistic regression analysis, focal motor deficit at admission was the
      most important predictor of neurologic deficits at 1 year. GCS score predicted
      the cognitive and motor sequelae. Neurological sequelae at year occurred in 78.5%
      patients with TBM in the form of cognitive impairment, motor deficit and optic
      atrophy. Sequelae were common in patients who had focal motor deficit and altered
      sensorium at admission.

PMID- 17222111
TI  - Myasthenia gravis in pregnancy and birth: identifying risk factors, optimising
      care.
AB  - Women with myasthenia gravis (MG) have increased risk of pregnancy complications
      and an adverse pregnancy outcome. This study examined risk factors for such
      complications in order to improve the care for pregnant MG women. Through the
      Medical Birth Registry of Norway, 73 MG mothers with 135 births were identified.
      Their obstetrical and clinical records were examined. Data on pregnancy, delivery
      and the newborn were combined with information on mother's disease. The risk for
      neonatal MG was halved if the mother was thymectomized (P = 0.03). Children with
      neonatal MG were more likely to display signs of foetal distress during delivery
      (P = 0.05). Only in one-third of the pregnancies did the patient see a
      neurologist during pregnancy. These patients used MG medication more often during
      pregnancy (P = 0.001), and were more likely to be thymectomized (P = 0.007). They
      also had a higher rate of elective sections (P = 0.009). Thymectomy may have a
      protective effect against neonatal MG. Neonatal MG can cause foetal distress
      during delivery. Most MG women benefit from being examined by a neurologist
      during pregnancy, to minimize risks and select the best delivery mode in
      collaboration with obstetricians.

PMID- 17222112
TI  - Mitochondrial DNA variants in Bulgarian patients affected by multiple sclerosis.
AB  - The occurrence of multiple sclerosis (MS) in subjects clustering to a particular
      mitochondrial DNA (mtDNA) haplogroup/haplotype or carrying mtDNA mutations
      associated with Leber's hereditary optic neuropathy (LHON) has suggested that
      mitochondrial genome may contribute to susceptibility to MS. In the present
      study, 58 unrelated Bulgarian patients with relapsing remitting form of MS and
      104 randomly selected healthy individuals were analysed for the presence of 14
      mtDNA polymorphisms determining major European haplogroups as well as three
      (4216, 14 798, 13 708) secondary LHON mutations. Restriction enzyme analysis used
      to screen patients and controls for the common haplogroup-associated
      polymorphisms showed that each of these changes was present in MS patients at a
      similar frequency to control subjects. However, 21 of the 58 patients (36.2%)
      were positive for T4 216C mutation, while only 11.3% of the controls carried this
      secondary LHON base change (P < 0.01; OR = 4.38). Our finding indicated that
      4216C base substitution could be considered as a predisposing marker for MS and
      supported the hypothesis that particular mtDNA variants could contribute to
      genetic susceptibility of MS, and merits further investigation.

PMID- 17222113
TI  - Saddle sensation is preserved in a few patients with cauda equina or conus
      medullaris lesions.
AB  - Although saddle sensory deficit seems the most useful clinical sign in the
      diagnosis of a cauda equina or conus medullaris lesion, findings of previous
      studies were controversial. The aim of the present study was to try to resolve
      this issue. The data from the author's series of patients with clinical,
      electrodiagnostic and radiological findings compatible with a cauda equina lesion
      were reviewed. Of the 117 patients in the series, 11 (10 men) did not have a
      saddle sensory deficit. These 11 patients had less severe sacral dysfunction than
      the others, and none of them needed urgent surgical intervention. They all had
      electromyographic (EMG) signs of a significant motor fibre lesion, and in seven
      men the sacral (penilo-cavernosus) reflex was clinically abnormal. The study
      revealed normal saddle sensation in approximately 10% of patients with cauda
      equina or conus medullaris lesions. Dissociation between preserved touch
      sensation and abnormal EMG findings, as well as dissociation between preserved
      touch sensation and a non-elicitable penilo-cavernosus reflex might be explained
      by preservation of the thinner sensory nerve fibres, which are more resistant to
      compression. Although, saddle sensory loss seems to identify patients who might
      benefit from urgent spinal imaging and surgery, further diagnostic evaluation is
      also indicated in patients with normal saddle sensation, particularly due to the
      increased frequency of spinal tumours found in this subgroup.

PMID- 17222114
TI  - Anosognosia versus unilateral neglect. Coexistence and their relations to age,
      stroke severity, lesion site and cognition.
AB  - The aim of this study was to examine the association between anosognosia and
      unilateral neglect (UN), with special focus on age, stroke severity, lesion
      location and pre-stroke dementia. The basis of this investigation was a
      population-based stroke incidence study. Anosognosia was assessed using a
      questionnaire, and UN using a three-item version of the Behaviour Inattention
      Test, the Baking Tray Task and a test of personal neglect. Stroke severity was
      assessed using the NIH stroke scale. Patients with anosognosia were older, and
      they more often had pre-stroke dementia than patients having UN only. No
      particular lesion localization was associated with anosognosia, while UN was
      strongly associated with previously defined lesion sites, often in the parietal
      lobe. There was a borderline significance regarding stroke severity in patients
      having anosognosia compared with those with UN only. Patients with anosognosia
      had higher mortality than patients without, but when controlled for age and
      stroke severity, this effect was not independent. While UN is closely associated
      with 'classical' lesion sites, anosognosia is a condition that more often occurs
      in a previously impaired brain. For anosognosia, lesion location appears to be
      less important. Anosognosia also tends to occur with larger strokes.

PMID- 17222115
TI  - Post-polio syndrome patients treated with intravenous immunoglobulin: a double
      blinded randomized controlled pilot study.
AB  - Post-polio syndrome (PPS) is characterized by new muscle weakness, atrophy,
      fatigue and pain developing several years after the acute polio. Some studies
      suggest an ongoing inflammation in the spinal cord in these patients. From this
      perspective, intravenous immunoglobulin (IvIg) could be a therapeutic option. We
      performed a double-blinded randomized controlled pilot study with 20 patients to
      investigate the possible clinical effects of IvIg in PPS. Twenty patients were
      randomized to either IvIg 2 g/kg body weight or placebo. Primary endpoints were
      changes in pain, fatigue and muscle strength 3 months after treatment. Surrogate
      endpoints were changes in cerebrospinal fluid (CSF) cytokine levels. Secondary
      endpoints were pain, fatigue and isometric muscle strength after 6 months.
      Patients receiving IvIg reported a significant improvement in pain during the
      first 3 months, but no change was noted for subjective fatigue and muscle
      strength. CSF levels of tumour necrosis factor-alpha (TNF-alpha) were increased
      compared with patients with non-inflammatory neurological disorders. In
      conclusion, in this small pilot study no effect was seen with IvIg treatment on
      muscle strength and fatigue, however IvIg treated PPS patients reported
      significantly less pain 3 months after treatment. TNF-alpha was increased in the
      CSF from PPS patients. The results are promising, but not conclusive because of
      the low number of patients studied.

PMID- 17222116
TI  - Progression of dysautonomia in multiple system atrophy: a prospective study of
      self-perceived impairment.
AB  - To assess severity and progression of self-perceived dysautonomia and their
      impact on health-related quality of life (Hr-QoL) in multiple system atrophy
      (MSA), twenty-seven patients were recruited by the European MSA Study Group (EMSA
      SG). At baseline, all patients completed the Composite Autonomic Symptom Scale
      (COMPASS) and the 36 item Short Form Health Survey (SF-36), and they were
      assessed using the 3-point global disease severity scale (SS-3) and the Unified
      MSA Rating Scale (UMSARS). After 6 months follow-up, the self completed COMPASS
      Change Scale (CCS), the SF-36, SS-3, and UMSARS were obtained. MSA patients
      showed marked self-perceived dysautonomia at baseline visit and pronounced
      worsening of dysautonomia severity on the CCS at follow-up. Severity and
      progression of dysautonomia did not correlate with age, disease duration, motor
      impairment and overall disease severity at baseline. There were no significant
      differences between genders and motor subtypes. Baseline COMPASS scores were,
      however, inversely correlated with SF-36 scores. Progression of self-perceived
      dysautonomia did not correlate with global disease progression. Hr-QoL scores
      were stable during follow-up. This is the first study to investigate self
      perceived dysautonomia severity in MSA and its evolution over time. Our data
      suggest that dysautonomia should be recognized as a key target for therapeutic
      intervention in MSA.

PMID- 17222117
TI  - Hormone replacement therapy and headache prevalence in postmenopausal women. The
      Head-HUNT study.
AB  - Conflicting evidence exists whether hormone replacement therapy (HRT) is a risk
      factor for headache. The aim of the study was to examine the prevalence of
      headache and migraine amongst postmenopausal women using HRT. In the Nord
      Trondelag Health Study 1995-97 (HUNT 2), 18,323 (62%) out of 29,679 women aged 40
      years or more responded to headache questions (Head-HUNT). Amongst the 6007
      postmenopausal women, 5507 (92%) responded to questions regarding use of HRT
      (2375 used or had used it) and questions related to headache (2407 had
      complaints). There was a significant association between headache and present use
      of HRT, both with local [odds ratio (OR) = 1.4, 95% confidence intervals (CI) 1.1
      1.7] and systemic (OR = 1.6, 95% CI 1.4-1.9) application. This was found for non
      migrainous headache (OR = 1.3, 95% CI 1.1-1.5) and migraine (OR = 1.6, 95% CI 1.4
      1.9). Both migraine and non-migrainous headache were more probably amongst users
      of postmenopausal HRT than amongst those who had never used HRT. Whether HRT
      caused headache or was used partly because of headache cannot be determined in
      this cross-sectional study.

PMID- 17222118
TI  - Telephone follow-up for patients with amyotrophic lateral sclerosis.
AB  - The relentless evolution of amyotrophic lateral sclerosis (ALS), a severe
      neurodegenerative disorder of the upper and lower motoneurons, leads to an
      increasing level of disability. Most patients, during the course of the disease,
      become unable to attend the tertiary clinical care center and are thus prevented
      from enrolling in clinical trials or benefiting from specialized care and
      management. The main objective of this study was to verify whether the ALS
      functional rating scale (ALSFRS) could be reliably administered by telephone to
      patients, when unable to attend the ALS clinic, or to their caregivers. ALSFRS is
      a validated instrument that assesses the functional status and the disease
      progression in ALS. We first administered the functional rating scale directly in
      the clinic to 30 patients, with definite or probable ALS, and to their respective
      caregivers, and found a very high agreement between the two groups for the total
      score and the majority of the rating items. Next, we showed, in both patients and
      caregivers, a high degree of correlation between the total score of the ALSFRS
      measured by telephone and that reported in the clinic. This indicates that ALSFRS
      is a reliable instrument for monitoring the disease progression in homebound
      patients, even when the person contacted by telephone is the caregiver. We also
      performed a telephone clinic, based on an unstructured interview, with 16 ALS
      patients at an advanced stage of the disease and unable to attend the ALS clinic.
      On some occasions, the person interviewed was the caregiver. The symptoms most
      frequently reported were a worsening of muscle strength, swallowing and breathing
      problems, constipation, and inability to clear lung secretions. Several patients
      asked for assistive and adaptive equipment. All patients and caregivers found the
      telephone clinic very useful and considered it a good complement to the
      management and care programme.

PMID- 17222119
TI  - Combination of IFN beta-1a (Avonex) and mycophenolate mofetil (Cellcept) in
      multiple sclerosis.
AB  - To determine the safety of a combination of mycophenolate mofetil (Cellcept, MMF)
      and IFNbeta-1a (Avonex) in relapsing-remitting multiple sclerosis (RRMS) and to
      evaluate the effects of the combination on clinical and magnetic resonance
      imaging (MRI) measures of disease activity. Secondary objectives were clinical
      and MRI data. An open-label, single-centre study including 30 RRMS patients was
      performed. Inclusion criteria were patients expanded disability status scale
      (EDSS) score <6.0, treated by Avonex for at least 6 months, with at least two
      relapses during the previous 2 years and at least one during the previous 6
      months. MMF at a progressive dose of 2 g per day orally was added to Avonex for a
      duration of 6 months. MRI data were obtained at baseline and at the end of the
      study. The pre-study annual relapse rate was 2.0 +/- 0.7 and the EDSS score at
      baseline was 2.9 +/- 1.3. Eleven patients had gadolinium (Gd)-enhanced lesions at
      baseline for a total number of 35 lesions. Two patients interrupted the
      combination, one after the first dose for personal reasons unrelated to the study
      and the other due to diarrhoea. A few of the patients also reported nausea and
      abdominal pains. Adverse events included benign infectious diseases, insomnia and
      dizziness. No significant biological abnormalities were noted. The annualized
      relapse rate was 0.57 +/- 0.3 at the end of the study (P < 0.001). The mean EDSS
      score was 2.6 +/- 1.5 and no Gd-enhanced lesions were detected on MRI at the end
      of the study. MMF and IFNbeta-1a (Avonex) combined therapy is safe and very well
      tolerated. Clinical and MRI data suggest that this combination may be beneficial.

PMID- 17222120
TI  - The seizure outcome after amygdalohippocampectomy and temporal lobectomy.
AB  - The aim of this study was to compare the seizure outcome of two different types
      of epilepsy surgery, selective amygdalohippocampectomy (AHE) and anterior
      temporal lobectomy (ATLE) in patients with temporal lobe epilepsy. We included
      114 patients who had mesio-temporal lobe epilepsy and hippocampal sclerosis or
      gliosis on histology. Patients had ATLE if the non-dominant hemisphere was
      affected or if the whole temporal lobe was atrophic. Patients had AHE if the
      dominant hemisphere was affected. Standardized seizure outcome at 1 year
      following surgery was used. Overall 40% of the 114 patients who had temporal lobe
      epilepsy surgery were seizure-free at 1-year (Engel's class Ia). A good outcome
      (Engel's classes I and II) was significantly more frequent in ATLE than in AHE.
      (66% and 44%, respectively, P = 0.03). ATLE had a better seizure outcome than
      AHE.

PMID- 17222121
TI  - Subinsular vascular lesions: an analysis of 119 consecutive autopsied brains.
AB  - The insula of Reil constitutes a functionally intriguing complex of the brain
      related to multifunctional activities. We examined the subinsular region in 119
      consecutively autopsied patients, as T2 hyperintense lesions are frequently
      observed in magnetic resonance diagnosis of this region. The patients were
      admitted in neurology wards and were diagnosed as having cerebrovascular disease
      in 55 patients (46%), other neurological diseases in 57 patients (48%) and non
      neurological diseases in seven patients (6%). Demyelination of the white matter
      was semi-quantified as a fiber density score (percent stained area/total area)
      with computer-assisted image analysis on Kluver-Barrera-stained sections.
      Astrogliosis was assessed by immunohistochemistry for glial fibrillary acidic
      protein. The lesion analysis showed a dilated perivascular space in 29 patients
      (24%), demyelination (fiber density score less than the mean - 1 SD) in 27
      patients (23%), slit-shaped lesion in six patients (5%), lacunar infarction in
      one patient (1%) and cerebral hemorrhage in one patient (1%). A histologic
      radiologic comparison in two patients with subcortical ischemic vascular dementia
      showed correspondence between subinsular hyperintensities, and demyelination,
      gliosis and a dilated perivascular space. These results indicate that subinsular
      lesions rarely signifies focal vascular lesions, and are consisted of
      demyelination, gliosis and a dilated perivascular space.

PMID- 17222122
TI  - The Category Cued Recall test in very mild Alzheimer's disease: discriminative
      validity and correlation with semantic memory functions.
AB  - Episodic memory tests that measure cued recall may be particularly effective in
      the diagnosis of early Alzheimer's disease (AD) because they examine both
      episodic and semantic memory functions. The Category Cued Recall (CCR) test
      provides superordinate semantic cues at encoding and retrieval, and high
      discriminative validity has been claimed for this test. The aim of this study was
      to investigate the discriminative validity for this test when compared with the
      10-word memory list from Alzheimer's Disease Assessment Scale (ADAS-cog) that
      measures free recall. The clinical diagnosis of AD was taken as the standard. It
      was also investigated whether the two episodic memory tests correlated with
      measures of semantic memory. The tests were administered to 35 patients with very
      mild AD (Mini Mental State Examination score >22) and 28 control subjects. Both
      tests had high sensitivity (>88%) with high specificity (>89%). One out of the
      five semantic memory tests was significantly correlated to performances on CCR,
      whereas delayed recall on the ADAS-cog memory test was significantly correlated
      to two semantic tests. In conclusion, the discriminative validity of the CCR test
      and the ADAS-cog memory test was equivalent in very mild AD. This may be because
      CCR did not tap more semantic processes, which are impaired in the earliest
      phases of AD, than a test of free recall.

PMID- 17222123
TI  - Middle cerebral artery dolichoectasia in a young woman with a previous stroke.
AB  - We observed a 32-year-old female who had suffered from a left hemisphere ischemic
      stroke with right hemiparesis at the age of seven. At that time, a CT scan
      demonstrated a left ischemic lesion in nucleo-capsular region and a cerebral
      angiogram documented a complete occlusion of the supraclinoid segment of the
      internal carotid artery. When we observed the patient neurological examination
      demonstrated a moderate right brachio-crural hemiparesis. A brain MRI showed an
      old ischemic lesion involving the left nucleo-capsular and 'flow voids'
      suggestive for a vascular malformation in the left sylvian region. A cerebral
      rotational angiogram with 3-D reconstructions demonstrated a dolichoectatic left
      middle cerebral artery with an unusual 'corkscrew' aspect. Middle cerebral artery
      dolichoectasia is a rare pathological condition that may manifest with a stroke.
      The patients with intracranial arterial dolichoectasia (IADE) are most often
      hypertensive elderly men, and, to the best of our knowledge, an ischemic stroke
      associated with IADE has never been reported in children.

PMID- 17222124
TI  - Avellis syndrome due to borreliosis.
AB  - Avellis syndrome is a rare form of alternating hemiparesis that is usually
      because of atherosclerosis. We report a 67-year-old man who developed
      paresthesiae of the left arm, dysphagia and dysphonia. The clinical picture,
      magnetic resonance imaging and cerebrospinal fluid findings were consistent with
      Avellis syndrome caused by brain stem arteritis because of late stage Borrelia
      burgdorferi infection, an extremely unusual aetiology for Avellis syndrome; this
      may well be the first such instance. It may be unrecognized in elderly patients
      with other risk factors for cerebrovascular disease.

PMID- 17222125
TI  - Bilateral hand amyotrophy with PMP-22 gene deletion.
AB  - Hereditary neuropathy with liability to pressure palsies (HNPP) phenotypes are
      heterogeneous. We report the case of a 52-year-old woman without medical history,
      who complained of bilateral hand weakness suggestive first of a motor neuron
      disorder. The presence of a diffuse predominant distal demyelinating neuropathy
      suggested a deletion of PMP-22 gene, which was confirmed by genetic analysis.
      This case report underlines a novel phenotype related to the deletion of PMP-22
      gene.

PMID- 17222126
TI  - rFVIIa--for acute rebleeding of a cerebral cavernous malformation.
AB  - Recurrent bleeding episodes of cavernomas especially in the brainstem can cause
      progressive neurological deficits. Therefore brainstem cavernomas are still a
      therapeutic dilemma and a treatment challenge for the neuro critical care
      community. We report a 39-year-old woman with spontaneous ataxia diplopia and
      vomiting, who has been treated for multiple intracerebral cavernomas during the
      last 10 years. A cerebral computed tomography (cCT) revealed a re-bleeding
      cavernoma in the left cerebral peduncle with consecutive obstructive
      hydrocephalus. As a result of the difficult anatomical location, no surgical
      approach was possible. As an off-label treatment, recombinant activated factor
      VII (rFVIIa) was administered to prevent possible further bleeding and especially
      further sequelae. The patient recovered well and no adverse events and especially
      no further bleeding of the cavernoma were observed. To our knowledge, this is the
      first report of the safe and successful use of rFVIIa to treat re-bleeding
      episodes in cavernomas. Further clinical studies are needed to specify the future
      potential of rFVIIa.

PMID- 17222127
TI  - Using archaeal genomics to fight global warming and clostridia to fight cancer.

PMID- 17222128
TI  - Key role of selective viral-induced mortality in determining marine bacterial
      community composition.
AB  - Viral infection is thought to play an important role in shaping bacterial
      community composition and diversity in aquatic ecosystems, but the strength of
      this interaction and the mechanisms underlying this regulation are still not well
      understood. The consensus is that viruses may impact the dominant bacterial
      strains, but there is little information as to how viruses may affect the less
      abundant taxa, which often comprise the bulk of the total bacterial diversity.
      The potential effect of viruses on the phylogenetic composition of marine
      bacterioplankton was assessed by incubating marine bacteria collected along a
      North Pacific coastal-open ocean transect in seawater that was greatly depleted
      of ambient viruses. The ambient communities were dominated by typical marine
      groups, including alphaproteobacteria and the Bacteroidetes. Incubation of these
      communities in virus-depleted ambient water yielded an unexpected and dramatic
      increase in the relative abundance of bacterial groups that are generally
      undetectable in the in situ assemblages, such as betaproteobacteria and
      Actinobacteria. Our results suggest that host susceptibility is not necessarily
      only proportional to its density but to other characteristics of the host, that
      rare marine bacterial groups may be more susceptible to viral-induced mortality,
      and that these rare groups may actually be the winners of competition for
      resources. These observations are not inconsistent with the 'phage kills the
      winner' hypothesis but represent an extreme and yet undocumented case of this
      paradigm, where the potential winners apparently never actually develop beyond a
      very low abundance threshold in situ. We further suggest that this mode of
      regulation may influence not just the distribution of single strains but of
      entire phylogenetic groups.

PMID- 17222129
TI  - Microbial communities in a porphyry copper tailings impoundment and their impact
      on the geochemical dynamics of the mine waste.
AB  - The distribution and diversity of acidophilic bacteria of a tailings impoundment
      at the La Andina copper mine, Chile, was examined. The tailings have low sulfide
      (1.7% pyrite equivalent) and carbonate (1.4% calcite equivalent) contents and are
      stratified into three distinct zones: a surface (0-70-80 cm) 'oxidation zone'
      characterized by low-pH (2.5-4), a 'neutralization zone' (70-80 to 300-400 cm)
      and an unaltered 'primary zone' below 400 cm. A combined cultivation-dependent
      and biomolecular approach (terminal restriction enzyme fragment length
      polymorphism and 16S rRNA clone library analysis) was used to characterize the
      indigenous prokaryotic communities in the mine tailings. Total cell counts showed
      that the microbial biomass was greatest in the top 125 cm of the tailings. The
      largest numbers of bacteria (10(9) g(-1) dry weight of tailings) were found at
      the oxidation front (the junction between the oxidation and neutralization
      zones), where sulfide minerals and oxygen were both present. The dominant iron
      /sulfur-oxidizing bacteria identified at the oxidation front included bacteria of
      the genus Leptospirillum (detected by molecular methods), and Gram-positive iron
      oxidizing acidophiles related to Sulfobacillus (identified both by molecular and
      cultivation methods). Acidithiobacillus ferrooxidans was also detected, albeit in
      relatively small numbers. Heterotrophic acidophiles related to Acidobacterium
      capsulatum were found by molecular methods, while another Acidobacterium-like
      bacterium and an Acidiphilium sp. were isolated from oxidation zone samples. A
      conceptual model was developed, based on microbiological and geochemical data
      derived from the tailings, to account for the biogeochemical evolution of the
      Piuquenes tailings impoundment.

PMID- 17222130
TI  - X-ray absorption spectroscopy (XAS) of toxic metal mineral transformations by
      fungi.
AB  - Fungi can be highly efficient biogeochemical agents and accumulators of soluble
      and particulate forms of metals. This work aims to understand some of the physico
      chemical mechanisms involved in toxic metal transformations focusing on the
      speciation of metals accumulated by fungi and mycorrhizal associations. The
      amorphous state or poor crystallinity of metal complexes within biomass and
      relatively low metal concentrations make the determination of metal speciation in
      biological systems a challenging problem but this can be overcome by using
      synchrotron-based element-specific X-ray absorption spectroscopy (XAS)
      techniques. In this research, we have exposed fungi and ectomycorrhizas to a
      variety of copper-, zinc- and lead-containing minerals. X-ray absorption
      spectroscopy studies revealed that oxygen ligands (phosphate, carboxylate) played
      a major role in toxic metal coordination within the fungal and ectomycorrhizal
      biomass during the accumulation of mobilized toxic metals. Coordination of toxic
      metals within biomass depended on the fungal species, initial mineral
      composition, the nitrogen source, and the physiological state/age of the fungal
      mycelium.

PMID- 17222131
TI  - Molecular characterization of Vibrio harveyi bacteriophages isolated from
      aquaculture environments along the coast of India.
AB  - Seven bacteriophages specific to Vibrio harveyi, the causative agent of luminous
      vibriosis in shrimp, were isolated from coastal aquaculture systems like shrimp
      farms, hatcheries and tidal creeks along the east and west coast of India. All
      the seven phages were found to have the typical head and tail morphology with
      double-stranded DNA as genetic material. Morphologically, six phages were grouped
      under family Siphoviridae and one under Myoviridae. These phages were further
      characterized with respect to host range, morphology and structural proteins.
      Genomic fingerprinting was carried out using restriction fragment length
      polymorphism (RFLP) and randomly amplified polymorphic DNA (RAPD). Major capsid
      proteins of all the phages detected by SDS-PAGE were distinct from one another.
      All the phages were found to be highly lytic for V. harveyi and had different
      lytic spectrum for the large number of isolates tested. Six of the seven phages
      isolated had a broad lytic spectrum and could be potential candidates for
      biocontrol of V. harveyi in aquaculture systems.

PMID- 17222132
TI  - Temporal gene-expression in Escherichia coli K-12 biofilms.
AB  - Analysis of the temporal development of Escherichia coli K-12 biofilms in complex
      medium indicates the greatest differential gene expression between biofilm and
      suspension cells occurred in young biofilms at 4 and 7 h (versus 15 and 24 h).
      The main classes of genes differentially expressed (biofilm versus biofilm and
      biofilm versus suspension cells) include 42 related to stress response (e.g.
      cspABFGI), 66 related to quorum sensing (e.g. ydgG, gadABC, hdeABD), 20 related
      to motility (e.g. flgBCEFH, fliLMQR, motB), 13 related to fimbriae (e.g. sfmCHM,
      fimZ, csgC), 24 related to sulfur and tryptophan metabolism (e.g. trpLBA, tnaLA,
      cysDNCJH), 80 related to transport (e.g. gatABC, agaBC, ycjJ, ydfJ, phoU,
      phnCJKM), and six related to extracellular matrix (e.g. wcaBDEC). Of the 93
      mutants identified and studied, 76 showed altered biofilm formation. Biofilm
      architecture changed from thin and dense to globular and dispersed to dense and
      smooth. The quorum-sensing signal AI-2 controls gene expression most clearly in
      mature biofilms (24 h) when intracellular AI-2 levels are highest. Sulfate
      transport and metabolism genes (cysAUWDN) and genes with unknown functions
      (ymgABCZ) were repressed in young (4, 7 h) biofilms, induced in developed
      biofilms (15 h), and repressed in mature (24 h) biofilms. Genes related to both
      motility and fimbriae were induced in biofilms at all sampling time points and
      colanic acid genes were induced in mature biofilms (24 h). Genes related to
      dihydroxyacetone phosphate synthesis from galactitol and galactosamine (e.g.
      gatZABCDR, agaBCY) were highly regulated in biofilms. Genes involved in the
      biosynthesis of indole and sulfide (tnaLA) are repressed in biofilms after 7 h
      (corroborated by decreasing intracellular indole concentrations in biofilms).
      Cold-shock protein transcriptional regulators (cspABFGI) appear to be positive
      biofilm regulators, and deletions in respiratory genes (e.g. hyaACD, hyfCG, appC,
      narG) increased biofilm formation sevenfold.

PMID- 17222133
TI  - Endosymbiosis in statu nascendi: close phylogenetic relationship between
      obligately endosymbiotic and obligately free-living Polynucleobacter strains
      (Betaproteobacteria).
AB  - Bacterial strains affiliated to the phylogenetically shallow subcluster C (PnecC)
      of the Polynucleobacter cluster, which is characterized by a minimal 16S rRNA
      gene sequence similarity of approximately 98.5%, have been reported to occur as
      obligate endosymbionts of ciliates (Euplotes spp.), as well as to occur as free
      living cells in the pelagic zone of freshwater habitats. We investigated if these
      two groups of closely related bacteria represent strains fundamentally differing
      in lifestyle, or if they simply represent different stages of a facultative
      endosymbiotic lifestyle. The phylogenetic analysis of 16S rRNA gene and 16S-23S
      ITS sequences of five endosymbiont strains from two different Euplotes species
      and 40 pure culture strains demonstrated host-species-specific clustering of the
      endosymbiont sequences within the PnecC subcluster. The sequences of the
      endosymbionts showed characteristics indicating an obligate endosymbiotic
      lifestyle. Cultivation experiments revealed fundamental differences in
      physiological adaptations, and determination of the genome sizes indicated a
      slight size reduction in endosymbiotic strains. We conclude that the two groups
      of PnecC bacteria represent obligately free-living and obligately endosymbiotic
      strains, respectively, and do not represent different stages of the same complex
      life cycle. These closely related strains occupy completely separated ecological
      niches. To our best knowledge, this is the closest phylogenetic relationship
      between obligate endosymbionts and obligately free-living bacteria ever revealed.

PMID- 17222135
TI  - Vibrio anguillarum colonization of rainbow trout integument requires a DNA locus
      involved in exopolysaccharide transport and biosynthesis.
AB  - Vibrio anguillarum, part of the normal flora of the aquatic milieu, causes a
      fatal haemorrhagic septicaemia in marine fish. In this study, a rainbow trout
      model was used to characterize the colonization of fish skin by V. anguillarum.
      Within 5 h after infection, the bacterium penetrated the skin mucosal layer,
      attached to the scales within 12 h, and formed a biofilm by 24-48 h. Two
      divergently transcribed putative operons, orf1-wbfD-wbfC-wbfB and wza-wzb-wzc,
      were shown to play a role in skin colonization and virulence. The first operon
      encodes proteins of unknown function. The wza-wzb-wzc genes encode a secretin,
      tyrosine kinase and tyrosine phosphatase, respectively, which are similar to
      proteins in polysaccharide transport complexes. Compared with the wild type,
      polar mutations in wza, orf1 and wbfD caused a decrease in exopolysaccharide
      biosynthesis but not lipopolysaccharide biosynthesis. The wza and orf1 mutants
      did not attach to fish scales; whereas, the wbfD mutant had a wild-type
      phenotype. Moreover, the wza and orf1 mutants had decreased exoprotease activity,
      in particular the extracellular metalloprotease EmpA, as well as mucinase
      activity suggesting that these mutations also affect exoenzyme secretion. Thus,
      the exopolysaccharide transport system in V. anguillarum is required for
      attachment to fish skin, possibly preventing mechanical removal of bacteria via
      natural sloughing of mucus.

PMID- 17222134
TI  - Synchronization of cell death in a dinoflagellate population is mediated by an
      excreted thiol protease.
AB  - Regulated programmed cell death (PCD) processes have been documented in several
      phytoplankton species and are hypothesized to play a role in population dynamics.
      However, the mechanisms leading to the coordinated collapse of phytoplankton
      blooms are poorly understood. We showed that the collapse of the annual bloom of
      Peridinium gatunense, an abundant dinoflagellate in Lake Kinneret, Israel, is
      initiated by CO2 limitation followed by oxidative stress that triggers a PCD-like
      cascade. We provide evidences that a protease excreted by senescing P. gatunense
      cells sensitizes younger cells to oxidative stress and may consequently trigger
      synchronized cell death of the population. Ageing of the P. gatunense cultures
      was characterized by a remarkable rise in DNA fragmentation and enhanced
      sensitivity to H2O2. Exposure of logarithmic phase (young) cultures to
      conditioning media from stationary phase (old) cells sensitized them to H2O2 and
      led to premature massive cell death. We detected the induction of specific
      extracellular protease activity, leupeptin-sensitive, in ageing cultures and in
      lake waters during the succession of the P. gatunense bloom. Partial purification
      of the conditioned media revealed that this protease activity is responsible for
      the higher susceptibility of young cells to oxidative stress. Inhibition of the
      protease activity lowered the sensitivity to oxidative stress, whereas
      application of papain to logarithmic phase P. gatunense cultures mimicked the
      effect of the spent media and enhanced cell death. We propose a novel mechanistic
      framework by which a population of unicellular phytoplankton orchestrates a
      coordinated response to stress, thereby determine the fate of its individuals.

PMID- 17222136
TI  - Bacterial degradation of airborne phenol in the phyllosphere.
AB  - Despite the vast surface area of terrestrial plant leaves and the large microbial
      communities they support, little is known of the ability of leaf-associated
      microorganisms to access and degrade airborne pollutants. Here, we examined
      bacterial acquisition and degradation of phenol on leaves by an introduced phenol
      degrader and by natural phyllosphere communities. Whole-cell gfp-based
      Pseudomonas fluorescens bioreporter cells detected phenol on leaves that had
      previously been transiently exposed to gaseous phenol, indicating that leaves
      accumulated phenol; moreover, they accumulated it in sites that were accessible
      to epiphytic bacteria and to concentrations that were at least 10-fold higher
      than those in the air. After inoculated leaves were exposed to gaseous 14C
      phenol, leaves harbouring the phenol-degrading Pseudomonas sp. strain CF600
      released eight times more 14CO2 than did leaves harbouring a non-degrading
      mutant, demonstrating that CF600 actively mineralized phenol on leaves. We
      evaluated phenol degradation by natural microbial communities on green ash leaves
      that were collected from a field site rich in airborne organic pollutants. We
      found that significantly more phenol was mineralized by these leaves when the
      communities were present than by these leaves following surface sterilization.
      Thus, phenol-degrading organisms were present in these natural communities and
      were metabolically capable of phenol degradation. Collectively, these results
      provide the first direct evidence that bacteria on leaves can degrade an organic
      pollutant from the air, and indicate that bacteria on leaves could potentially
      contribute to the natural attenuation of organic air pollutants.

PMID- 17222137
TI  - Ultrastructure of coccoid viable but non-culturable Vibrio cholerae.
AB  - Morphology of viable but non-culturable Vibrio cholerae was monitored for 2 years
      by scanning and transmission electron microscopy. Morphological changes included
      very small coccoid forms, after extended incubation at 4 degrees C and room
      temperature, and sequential transformation from curved rods to irregular
      (approximately 1 microm) rods to approximately 0.8 microm coccoid cells and,
      ultimately, to tiny coccoid forms (0.07-0.4 microm). Irregular rod-shaped and
      coccoid cells were equally distributed in microcosms during the first 30-60 days
      of incubation at both temperatures, but only coccoid cells were observed after
      incubation for 60 days at 4 degrees C. When V. cholerae O1 and O139, maintained
      for 30-60 days at both temperatures, were heated to 45 degrees C for 60 s, after
      serial passage through 0.45 microm and 0.1 microm filters, and plating on Luria
      Bertania (LB) agar, only cells larger than 1 microm yielded colonies on LB agar.
      Approximately 0.1% of heat-treated cultures were culturable. Cell division in the
      smallest coccoid cells was observed, yielding daughter cells of equal size,
      whereas other coccoid cells revealed bleb-like, cell wall evagination, followed
      by transfer of nuclear material. Coccoid cells of V. cholerae O1 and O139
      incubated at 4 degrees C for more than 1 year remained substrate responsive and
      antigenic.

PMID- 17222138
TI  - Diversity of the cadmium-containing carbonic anhydrase in marine diatoms and
      natural waters.
AB  - A recent report of a novel carbonic anhydrase (CDCA1) with Cd as its metal centre
      in the coastal diatom Thalassiosira weissflogii has led us to search for the
      occurrence of this Cd enzyme (CDCA) in other marine phytoplankton and in the
      environment. Using degenerate primers designed from the published sequences from
      T. weissflogii and a putative sequence in the genome of Thalassiosira pseudonana,
      we show that CDCA is widespread in diatom species and ubiquitous in the
      environment. All detected genes share more than 64% amino acid identity with the
      CDCA of T. pseudonana. Analysis of the amino acid sequence of CDCA shows that the
      putative Cd binding site resembles that of beta-class carbonic anhydrases (CAs).
      The prevalence of CAs in diatoms that presumably contain Cd at their active site
      probably reflects the very low concentration of Zn in the marine environment and
      the difficulty in acquiring inorganic carbon for photosynthesis. The cdca primers
      developed in this study should be useful for detecting cdca genes in the field,
      and studying the conditions under which they are expressed.

PMID- 17222139
TI  - Hypolithic community shifts occur as a result of liquid water availability along
      environmental gradients in China's hot and cold hyperarid deserts.
AB  - Hypolithic cyanobacterial communities occur in hot and cold hyperarid
      environments but the physical factors determining their diversity are not well
      understood. Here we report hypolithic diversity and colonization of a common
      quartz substrate at several hyperarid locations in the ancient deserts of north
      western China, that experience varying mean annual temperature, rainfall and
      concomitant availability of liquid water in soil. Microscopy and enrichment
      culture resulted only in Chroococcidiopsis morphotypes which were ubiquitous, but
      community phylogenetic analysis revealed considerable cyanobacterial and
      heterotrophic bacterial diversity. Species Richness and Shannon's Diversity Index
      displayed a significant positive linear correlation with availability of liquid
      water but not temperature or rainfall alone. Several taxonomic groups occurred
      only in specific climatically defined locations, while for Chroococcidiopsis,
      Deinococcus and Phormidium location specific lineages within these genera were
      also evident. Multivariate analysis was used to illustrate pronounced community
      shifts due to liquid water availability, although these did not significantly
      affect the predicted functional relationships within any given assemblage in
      either hot or cold, wet or dry hyperarid deserts. This study clearly demonstrates
      that availability of liquid water, rather than temperature or rainfall per se is
      the key determinant of hypolithic diversity in hyperarid locations, and
      furthermore that functionally similar yet taxonomically distinct communities
      occur, characterized by the presence of taxa that are specific to defined levels
      of aridity.

PMID- 17222140
TI  - Thioquinolobactin, a Pseudomonas siderophore with antifungal and anti-Pythium
      activity.
AB  - Under conditions of iron limitation Pseudomonas fluorescens ATCC 17400 produces
      two siderophores, pyoverdine, and a second siderophore quinolobactin, which
      itself results from the hydrolysis of the unstable molecule 8-hydroxy-4-methoxy-2
      quinoline thiocarboxylic acid (thioquinolobactin). Pseudomonas fluorescens ATCC
      17400 also displays a strong in vitro antagonism against the Oomycete Pythium,
      which is repressed by iron, suggesting the involvement of a siderophore(s). While
      a pyoverdine-negative mutant retains most of its antagonism, a thioquinolobactin
      negative mutant only slowed-down Pythium growth, and a double pyoverdine-,
      thioquinolobactin-negative mutant, which does not produce any siderophore,
      totally lost its antagonism against Pythium. The siderophore thioquinolobactin
      could be purified and identified from spent medium and showed anti-Pythium
      activity, but it was quickly hydrolysed to quinolobactin, which we showed has no
      antimicrobial activity. Analysis of antagonism-affected transposon mutants
      revealed that genes involved in haem biosynthesis and sulfur assimilation are
      important for the production of thioquinolobactin and the expression of
      antagonism.

PMID- 17222141
TI  - Isolation and characterization of hydrogen-oxidizing bacteria induced following
      exposure of soil to hydrogen gas and their impact on plant growth.
AB  - In many legumes, the nitrogen fixing root nodules produce H2 gas that diffuses
      into soil. It has been demonstrated that such exposure of soil to H2 can promote
      plant growth. To assess whether this may be due to H2-oxidizing microorganisms,
      bacteria were isolated from soil treated with H2 under laboratory conditions and
      from soils collected adjacent to H2 producing soybean nodules. Nineteen isolates
      of H2-oxidizing bacteria were obtained and all exhibited a half-saturation
      coefficient (Ks) for H2 of about 1 ml l(-1). The isolates were identified as
      Variovorax paradoxus, Flavobacterium johnsoniae and Burkholderia spp. using
      conventional microbiological tests and 16S rRNA gene sequence analysis. Seventeen
      of the isolates enhanced (57-254%) root elongation of spring wheat seedlings.
      Using an Arabidopsis thaliana bioassay, plant biomass was increased by 11-27%
      when inoculated by one of four isolates of V. paradoxus or one isolate of
      Burkholderia that were selected for evaluation. The isolates of V. paradoxus
      found in both H2-treated soil and in soil adjacent to soybean nodules had the
      greatest impact on plant growth. The results are consistent with the hypothesis
      that H2-oxidizing bacteria in soils have plant growth promoting properties.

PMID- 17222142
TI  - The bacterial storage compound poly-beta-hydroxybutyrate protects Artemia
      franciscana from pathogenic Vibrio campbellii.
AB  - Infections caused by antibiotic-resistant luminescent Vibrios can cause dramatic
      losses in aquaculture. In this study, the short-chain fatty acid beta
      hydroxybutyrate and its polymer poly-beta-hydroxybutyrate were investigated as
      possible new biocontrol agents. beta-Hydroxybutyrate was shown to completely
      inhibit the growth of pathogenic Vibrio campbelli at 100 mM. Moreover, the
      addition of 100 mM of this fatty acid to the culture water of Artemia nauplii
      infected with the V. campbelli strain significantly increased the survival of the
      nauplii. As Artemia is a non-selective and particle filter feeder, we also
      investigated whether poly-beta-hydroxybutyrate particles could be used to protect
      Artemia from the pathogenic V. campbellii. The addition of 100 mg l(-1) poly-beta
      hydroxybutyrate or more to the Artemia culture water offered a preventive and
      curative protection from the pathogen as a significantly enhanced survival was
      noticed. If added as a preventive treatment, a complete protection of infected
      nauplii (no significant mortality compared with uninfected nauplii) was observed
      at 1000 mg l(-1) poly-beta-hydroxybutyrate. Our data indicate that the use of
      poly-beta-hydroxybutyrate might constitute an ecologically and economically
      sustainable alternative strategy to fight infections in aquaculture.

PMID- 17222144
TI  - Plant-microbe association for rhizoremediation of chloronitroaromatic pollutants
      with Comamonas sp. strain CNB-1.
AB  - Comamonas sp. strain CNB-1, isolated from activated sludge and having a strong
      ability to degrade 4-chloronitrobenzene (4CNB), was applied for rhizoremediation
      of 4CNB-polluted soil through association with alfalfa. Confocal laser scanning
      microscopy revealed that strain CNB-1 successfully colonized alfalfa roots.
      Determination of strain CNB-1 populations by cultivation method and by
      quantitative competitive PCR technique targeting the chloronitrobenzene
      nitroreductase gene showed that the population of strain CNB-1 in the rhizosphere
      was about 10-100 times higher than that in the bulk soil. Gnotobiotic and outdoor
      experiments showed that pollutant 4CNB was completely removed within 1 or 2 days
      after 4CNB application into soil, and that its phytotoxicity to alfalfa was
      eliminated by inoculation of strain CNB-1. Results from PCR-denaturing gradient
      gel electrophoresis and analysis of 16S rRNA gene libraries revealed that the
      indigenous soil microbial community mainly consisted of alphaproteobacteria,
      betaproteobacteria, gammaproteobacteria, the CFB bacteria (Cytophaga
      Flavabacterium-Bacteriodes), and Acidobacteria. This microbial community was not
      significantly influenced by inoculation of strain CNB-1. Thus, this study has
      developed a Comamonas-alfalfa system for rhizoremediation of 4CNB.

PMID- 17222145
TI  - Spatial variation of active microbiota in the rice rhizosphere revealed by in
      situ stable isotope probing of phospholipid fatty acids.
AB  - This report is part of a serial study applying stable isotope labelling to rice
      microcosms to track the utilization of recently photosynthesized carbon by active
      microbiota in the rhizosphere. The objective of the present study was to apply
      phospholipid fatty acid-based stable isotope probing (PLFA-SIP) to detect the
      spatial variation of active microorganisms associated with rhizosphere carbon
      flow. In total, 49 pulses of 13CO2 were applied to rice plants in a microcosm
      over a period of 7 days. Rhizosphere soil was separated from bulk soil by a root
      bag. Soil samples were taken from rhizosphere and bulk soil, and the bulk soil
      samples were further partitioned both vertically (up layer and down layer) and
      horizontally with increasing distance to the root bag. Incorporation of 13C into
      PLFAs sharply decreased with distance to the roots. The labelling of 16:1omega9,
      18:1omega7, 18:1omega9, 18:2omega6,9 and i14:0 PLFAs was relatively stronger in
      the rhizosphere while that of i15:0 and i17:0 increased in the bulk soil. The
      microorganisms associated with 16:1omega9 were active in both up- and down-layer
      soils. The microorganisms represented by i14:0, 18:1omega7 and 18:2omega6,9
      exhibited a relatively higher activity in up-layer soil, whereas those
      represented by i15:0 and i17:0 were more active in down-layer soil. These results
      suggest that in the rhizosphere Gram-negative and eukaryotic microorganisms were
      most actively assimilating root-derived C, whereas Gram-positive microorganisms
      became relatively more important in the bulk soil. The active populations
      apparently differed between up- and down-layer soil and in particular changed
      with distance to the roots, demonstrating systematic changes in the activity of
      the soil microbiota surrounding roots.

PMID- 17222143
TI  - Analysis of environmental transcriptomes by DNA microarrays.
AB  - In this work we investigated the correlations between global gene expression
      patterns and environmental parameters in natural ecosystems. We studied the
      preferential gene expression of the iron oxidizer bacterium Leptospirillum
      ferrooxidans to adapt its physiology to changes in the physicochemical parameters
      in its natural medium. Transcriptome analysis by DNA microarrays can
      proportionate an instant picture about the preferential gene expression between
      two different environmental samples. However, this type of analysis is very
      difficult and complex in natural ecosystems, mainly because of the broad
      biodiversity and multiple environmental parameters that may affect gene
      expression. The necessity of high-quality RNA preparations as well as complicated
      data analysis are also technological limitations. The low prokaryotic diversity
      of the extremely acidic and iron-rich waters of the Tinto River (Spain)
      ecosystem, where L. ferrooxidans is abundant, allows the opportunity to achieve
      global gene expression studies and to associate gene function with environmental
      parameters. We applied a total RNA amplification protocol validated previously
      for the amplification of the environmental transcriptome (meta-transcriptome).
      The meta-transcriptome of two sites from the Tinto River mainly differing in the
      salt and oxygen contents were amplified and analysed by a L. ferrooxidans DNA
      microarray. The results showed a clear preferential induction of genes involved
      in certain physicochemical parameters like: high salinity (ectAB, otsAB), low
      oxygen concentration (cydAB), iron uptake (fecA-exbBD-tonB), oxidative stress
      (carotenoid synthesis, oxyR, recG), potassium (kdpBAC) or phosphate
      concentrations (pstSCAB), etc. We conclude that specific gene expression patterns
      can be useful indicators for the physiological conditions in a defined ecosystem.
      Also, the upregulation of certain genes and operons reveals information about the
      environmental conditions (nutrient limitations, stresses, etc.).

PMID- 17222146
TI  - Impact of carbon metabolism on 13C signatures of cyanobacteria and green non
      sulfur-like bacteria inhabiting a microbial mat from an alkaline siliceous hot
      spring in Yellowstone National Park (USA).
AB  - Alkaline siliceous hot spring microbial mats in Yellowstone National Park are
      composed of two dominant phototropic groups, cyanobacteria and green non-sulfur
      like bacteria (GNSLB). While cyanobacteria are thought to cross-feed low
      molecular-weight organic compounds to support photoheterotrophic metabolism in
      GNSLB, it is unclear how this could lead to the heavier stable carbon isotopic
      signatures in GNSLB lipids compared with cyanobacterial lipids found in previous
      studies. The two groups of phototrophs were separated using percoll density
      gradient centrifugation and subsequent lipid and stable carbon isotopic analysis
      revealed that we obtained fractions with a approximately 60-fold enrichment in
      cyanobacterial and an approximately twofold enrichment in GNSLB biomass,
      respectively, compared with the mat itself. This technique was used to study the
      diel cycling and 13C content of the glucose pools in and the uptake of 13C
      bicarbonate by the cyanobacteria and GNSLB, as well as the transfer of
      incorporated 13C from cyanobacteria to GNSLB. The results show that cyanobacteria
      have the highest bicarbonate uptake rates and accumulate glucose during the
      afternoon in full light conditions. In contrast, GNSLB have relatively higher
      bicarbonate uptake rates compared with cyanobacteria in the morning at low light
      levels. During the night GNSLB take up carbon that is likely derived through
      fermentation of cyanobacterial glucose enriched in 13C. The assimilation of 13C
      enriched cyanobacterial carbon may thus lead to enriched 13C-contents of GNSLB
      cell components.

PMID- 17222147
TI  - Linear relationship between Gaeumannomyces graminis var. tritici (Ggt) genotypic
      frequencies and disease severity on wheat roots in the field.
AB  - In order to investigate potential links existing between Gaeumannomyces graminis
      var. tritici (Ggt) population structure and disease development during polyetic
      take-all epidemics in sequences of Ggt host cereals, seven epidemics in fields
      with different cropping histories were monitored during the seasons 2001/2002
      (two fields), 2002/2003 (two fields) and 2003/2004 (three fields). Take-all
      incidence and severity were measured at stem elongation and Ggt populations were
      characterized. The 73 isolates collected in the two fields in 2001/2002 were
      distributed into two multilocus genotypes, G1 and G2 according to amplified
      fragment length polymorphism analysis. A monolocus molecular marker amplified by
      F-12 random amplification polymorphism DNA primer sizing between 1.9 and 2.0 kb
      that gave strictly the same distinction between the two multilocus genotypes was
      further applied to measure G1/G2 frequencies among Ggt populations in all fields
      (266 isolates). The ratios of G1 to G2 differed between fields with different
      cropping histories. A linear relationship between G2 frequency among Ggt
      populations and disease severity at stem elongation was measured during the three
      cropping seasons. When take-all decline was observed, G2 frequencies were low in
      first wheat crops, highest in short-term sequences and intermediate in longer
      sequences of consecutive crops of Ggt host cereals. This pattern could be the
      result of population selection by environmental conditions, in particular by
      microbial antagonism during the parasitic phase of the fungus. In order to better
      understand take-all epidemic dynamics, the distinction between these two
      genotypes could be a basis to develop models that link approaches of quantitative
      epidemiology and advances in population genetics of Ggt.

PMID- 17222148
TI  - Ecological control analysis: being(s) in control of mass flux and metabolite
      concentrations in anaerobic degradation processes.
AB  - Identification of the functional groups of microorganisms that are predominantly
      in control of fluxes through, and concentrations in, microbial networks would
      benefit microbial ecology and environmental biotechnology: the properties of
      those controlling microorganisms could be studied or monitored specifically or
      their activity could be modulated in attempts to manipulate the behaviour of such
      networks. Herein we present ecological control analysis (ECA) as a versatile
      mathematical framework that allows for the quantification of the control of each
      functional group in a microbial network on its process rates and concentrations
      of intermediates. In contrast to current views, we show that rates of flow of
      matter are not always limited by a single functional group; rather flux control
      can be distributed over several groups. Also, control over intermediate
      concentrations is always shared. Because of indirect interactions, through other
      functional groups, the concentration of an intermediate can also be controlled by
      functional groups not producing or consuming it. Ecological control analysis is
      illustrated by a case study on the anaerobic degradation of organic matter, using
      experimental data obtained from the literature. During anaerobic degradation,
      fermenting microorganisms interact with terminal electron-accepting
      microorganisms (e.g. halorespirers, methanogens). The analysis indicates that
      flux control mainly resides with fermenting microorganisms, but can shift to the
      terminal electron-accepting microorganisms under less favourable redox
      conditions. Paradoxically, halorespiring microorganisms do not control the rate
      of perchloroethylene and trichloroethylene degradation even though they catalyse
      those processes themselves.

PMID- 17222149
TI  - Passage through alternative hosts changes the fitness of Fusarium graminearum and
      Fusarium pseudograminearum.
AB  - Species of the necrotrophic fungal pathogen Fusarium that cause head blight and
      crown rot of cereals including wheat also infect a number of alternative host
      plants. This raises the prospect of more damaging pathogen strains originating
      and persisting as highly successful saprophytes on hosts other than wheat. The
      immediate impact on pathogenic (aggressiveness) and saprophytic (growth rate and
      fecundity) behaviour of six isolates with low, moderate or high initial
      aggressiveness was examined in two species of Fusarium after their passage
      through 10 alternative plant hosts. One passage through alternative hosts
      significantly reduced the pathogenic fitness of most isolates, but this change
      was not associated with a concomitant change in their overall saprophytic
      behaviour. The overall weak association between aggressiveness, fecundity and
      growth rate both before and after passage through the alternative hosts indicate
      that pathogenic and saprophytic fitness traits may be independently controlled in
      both Fusarium species. Thus, there was no trade-off between pathogenic and
      saprophytic fitness in these necrotrophic plant pathogens.

PMID- 17222150
TI  - Microbial community associated with the colonial ascidian Cystodytes
      dellechiajei.
AB  - The ascidian Cystodytes dellechiajei (Della Valle, 1877) (phylum Chordata, class
      Ascidiacea, family Polycitoridae) is a colonial tunicate that inhabits benthic
      rock environments in the Atlantic, Pacific and Indian Oceans, as well as the
      Mediterranean Sea. Its life cycle has two phases, the adult sessile colony and
      the free-living larva. Both adult zooids and larvae are surrounded by a
      protective tunic that contains several eukaryotic cell lines, is composed mainly
      of acidic mucopolysacharides associated with collagen and elastin-like proteins,
      and is covered by a thin cuticle. The microbiota associated with the tunic
      tissues of adult colonies and larva of C. dellechiajei has been examined by
      optical, confocal and electron microscopy and by fluorescence in situ
      hybridization (FISH), denaturing gradient gel electrophoresis (DGGE), and 16S
      rRNA gene clone library analysis. Microscopy analyses indicated the presence
      inside the tunic, both for the adult and the larva, of a dense community of
      Bacteria while only the external surface of colony cuticle was colonized by
      diatoms, rodophyte algae and prokaryotic-like epiphytes. Transmission electron
      microscopy showed tunic eukaryotic cells that were engulfing and lysing bacteria.
      16S rRNA gene analyses (DGGE and clone libraries) and FISH indicated that the
      community inside the tunic tissues of the adults and larvae was dominated by
      Alphaproteobacteria. Bacteria belonging to the phyla Gammaproteobacteria and
      Bacteroidetes were also detected in the adults. Many of the 16S rRNA gene
      sequences in the tunic tissues were related to known aerobic anoxygenic
      phototrophs (AAP), like Roseobacter sp. and Erythrobacter sp. In order to check
      whether the gene pufM, coding for the M subunit of the reaction centre complex of
      aerobic anoxygenic photosynthesis, was being expressed inside the ascidian
      tissues, two libraries, one for an adult colony and one for larva, of cDNA from
      the expressed pufM gene were also constructed. The sequences most frequently (64%
      for colony and 67% for larva) retrieved from these libraries presented > 90% aa
      identity with the pufM gene product of the Roseobacter-like group, a cluster of
      AAP widely detected in marine planktonic environments.

PMID- 17222151
TI  - Desulfurization of aromatic sulfonates by rhizosphere bacteria: high diversity of
      the asfA gene.
AB  - The plant growth-promoting effect of Pseudomonas putida S-313 is associated with
      its ability to desulfurize arylsulfonates. To understand this further, other
      plant-associated bacteria able to desulfurize a range of arylsulfonates were
      isolated from the rhizospheres of winter and spring barley. The isolates belonged
      to the beta-proteobacteria, including bacteria from the Variovorax paradoxus
      group and from the Acidovorax genus. They desulfurized toluenesulfonate to p
      cresol, and were found to contain orthologues of the P. putida S-313 asfA gene (>
      70% sequence identity to AsfA), which is required for aryldesulfonation in this
      species. Further putative asfA orthologues were identified in several bacteria
      and cyanobacteria whose genomes have been sequenced, but of these only
      Cupriavidus (Ralstonia) metallidurans was able to utilize arylsulfonates as
      sulfur source. Cultivation of V. paradoxus, C. metallidurans or P. putida S-313
      with toluenesulfonate as sulfur source led to a 100-fold increase in expression
      of the asfA homologues, which was largely repressed when sulfate was added.
      Polymerase chain reaction with degenerate primers was used to generate asfAB
      clone libraries from spring- and winter-barley rhizosphere DNA. Cluster analysis
      of 76 sequenced AsfA fragments revealed a broad diversity, with the majority of
      the sequences clustered together with AsfA from bacteria that are able to utilize
      toluenesulfonate as sulfur source. The diversity of asfA in barley rhizosphere
      underlines the importance of the desulfonation process for bacteria that inhabit
      the plant rhizosphere.

PMID- 17222152
TI  - Eukaryotic diversity associated with carbonates and fluid-seawater interface in
      Lost City hydrothermal field.
AB  - Lost City is a unique off-axis hydrothermal vent field characterized by highly
      alkaline and relatively low-temperature fluids that harbours huge carbonate
      chimneys. We have carried out a molecular survey based on 18S rDNA sequences of
      the eukaryotic communities associated with fluid-seawater interfaces and with
      carbonates from venting areas and the chimney wall. Our study reveals a variety
      of lineages belonging to eight major taxa: Metazoa, Fungi, Heterokonta
      (Stramenopiles), Alveolata, Radiolaria, Cercozoa, Heterolobosea and Euglenozoa.
      We detected one fungal lineage that appears to be widespread in hydrothermal
      systems both submarine and continental. Alveolates were the most abundant and
      diverse group in Lost City samples, although their distribution was very
      different in carbonate, where ciliates dominated, and in fluid-seawater
      libraries, where dinoflagellates, Group I and Group II (Syndiniales) marine
      alveolates were profuse. Similarly, Euglenozoa also displayed a differential
      distribution, kinetoplastids being present on carbonates and a novel group of
      diplonemids so far exclusively observed in the deep sea being dominant in fluid
      seawater libraries. Protist lineages identified in this ecosystem likely
      correspond to grazers, decomposers and parasites, playing key roles in the food
      web of the Lost City ecosystem.

PMID- 17222153
TI  - Residual polymerase activity-induced bias in terminal restriction fragment length
      polymorphism analysis.
AB  - Residual activity of polymerase chain reaction DNA polymerases in restriction
      analyses strongly affected genetic profiling based on terminal restriction
      fragment length polymorphisms. Artificial fragment sizes produced as a result of
      5'-overhang restriction site fill-in and addition of a terminal A may bias
      genetic profiling and genotyping of microbial communities. Efficient removal of
      polymerases retained original fragment sizes and significantly reduced this
      profiling bias in soil bacterial communities.

PMID- 17222155
TI  - Mental health screening in schools.
AB  - BACKGROUND: This article discusses the importance of screening students in
      schools for emotional/behavioral problems. METHODS: Elements relevant to planning
      and implementing effective mental health screening in schools are considered.
      Screening in schools is linked to a broader national agenda to improve the mental
      health of children and adolescents. Strategies for systematic planning for mental
      health screening in schools are presented. RESULTS: Mental health screening in
      schools is a very important, yet sensitive, agenda that is in its very early
      stages. Careful planning and implementation of mental health screening in schools
      offers a number of benefits including enhancing outreach and help to youth in
      need, and mobilizing school and community efforts to promote student mental
      health while reducing barriers to their learning. CONCLUSIONS: When implemented
      with appropriate family, school, and community involvement, mental health
      screening in schools has the potential to be a cornerstone of a transformed
      mental health system. Screening, as part of a coordinated and comprehensive
      school mental health program, complements the mission of schools, identifies
      youth in need, links them to effective services, and contributes to positive
      educational outcomes valued by families, schools, and communities.

PMID- 17222156
TI  - Children at risk: the association between perceived weight status and suicidal
      thoughts and attempts in middle school youth.
AB  - BACKGROUND: Suicide is one of the most common causes of death among young people.
      A report from the US Surgeon General called for strategies to prevent suicide,
      including increasing public awareness of suicide and risks factors, and enhancing
      research to understand risk and protective factors. Weight perception has been
      linked to depression and poor self-esteem in adolescents. The purpose of this
      study was to examine the relationship between perceived weight status and
      suicidal thoughts and actions by gender in middle school youth. METHODS: All
      public middle school students in 4 eastern North Carolina counties presented, and
      with parental permission (n = 5174), completed the Youth Risk Behavior Survey:
      Middle School Questionnaire. The 3 dependent variables were self-reported
      thinking, planning, and attempting suicide. Bivariate analyses describe suicidal
      thoughts and actions; multiple logistic regression models examined the
      relationship between weight description and suicidal thoughts and actions
      controlling for age, race, household composition, grades on report cards, and
      parents' education. RESULTS: Significantly more females than males reported
      thinking (26% vs 19%), planning (12% vs 9%), and attempting (11% vs 8%) suicide.
      For females, those who perceived themselves as overweight were significantly more
      likely to report suicidal thoughts and actions; while for males, perceptions of
      overweight and underweight were significantly associated with suicidal thoughts
      and actions. CONCLUSIONS: Controlling for personal and family characteristics,
      perceived weight status was significantly associated with suicidal thoughts and
      actions in middle school boys and girls.

PMID- 17222157
TI  - The contextual effect of school attachment on young adolescents' alcohol use.
AB  - BACKGROUND: The school is a primary context for social interaction, cultivation
      of interpersonal skills, formation of peer groups, self-expression, and
      development of self. Several studies have demonstrated that the social context of
      the school has important implications for determining the likelihood that an
      adolescent will follow a prosocial path through adolescence as opposed to
      becoming involved in delinquent behavior. METHODS: Using a data set of 4,216
      youth in 32 middle schools and junior high schools across the United States, this
      paper examines the effect of a student's own level of school attachment as well
      as the contextual level of school attachment (the normative level of school
      attachment in a school) on 5 alcohol-related measures: recent use of alcohol,
      intention to use alcohol, normative beliefs about peer use of alcohol, attitudes
      toward alcohol use, and aspirations consistent with alcohol use. RESULTS: This
      study demonstrates that regardless of a student's own level of school attachment,
      students who attend schools where the pupils overall tend to be well attached to
      school are less likely to use alcohol. In addition, they also have lower
      intentions to use alcohol, perceive that fewer of their peers at school use
      alcohol, and more strongly hold aspirations that are inconsistent with alcohol
      use. CONCLUSIONS: Our findings, along with the findings of related studies,
      provide support for the hypothesis that improvement of school climate may result
      in less substance use among students.

PMID- 17222158
TI  - A comparison of the Gatehouse Bullying Scale and the peer relations questionnaire
      for students in secondary school.
AB  - BACKGROUND: Bullying occurs in all schools. Measuring bullying in schools is
      complicated because both definitions of bullying and methods for measuring
      bullying vary. This study compared a brief 12-item Gatehouse Bullying Scale (GBS)
      with items drawn from the Peer Relations Questionnaire (PRQ), a well-established
      bullying questionnaire to measure the concurrent validity of the GBS. METHODS:
      Year 8 secondary school students (14 years of age) in metropolitan and regional
      Victoria, Australia, completed questionnaires assessing being teased, being
      deliberately left out, had rumors spread about oneself, and/or being physically
      threatened or hurt. RESULTS: The prevalence of bullying using GBS and PRQ was 57%
      and 61%, respectively. Percent agreement between the 2 measures was high.
      Agreement adjusted for chance was moderate (kappa 0.5). The GBS had good to
      moderate test-retest reliability (rho 0.65). CONCLUSIONS: The GBS is a short,
      reliable tool measuring the occurrence of bullying in schools. As well as a
      global estimate of bullying, the GBS provides estimates of 2 covert and 2 overt
      types of bullying which can be useful for schools to better plan interventions
      dealing with school bullying.

PMID- 17222159
TI  - Availability of high school extracurricular sports programs and high-risk
      behaviors.
AB  - BACKGROUND: The Surgeon General has called for an expansion of school-based
      extracurricular sports programs to address the obesity epidemic. However, little
      is known about the availability of and participation in high school
      extracurricular sports and how participation in these sports is related to high
      risk behaviors. METHODS: We surveyed Los Angeles County public high schools in
      2002 to determine the number of extracurricular sports programs offered and the
      percentage of students participating in those programs. We used community data on
      rates of arrests, births, and sexually transmitted diseases (STDs) among youth to
      examine associations between risk behaviors and participation in sports programs.
      RESULTS: The average school offered 14 sports programs, and the average
      participation rate was 39% for boys and 30% for girls. Smaller schools and
      schools with higher percentages of disadvantaged students offered fewer programs.
      The average school offering 13 or fewer programs had 14% of its students
      participating, while the average school offering 16 or more programs had 31% of
      its students participating in sports. Controlling for area-level demographics,
      juvenile arrest rates and teen birth rates, but not STD rates, were lower in
      areas where schools offered more extracurricular sports. CONCLUSIONS:
      Opportunities for participation in high school extracurricular sports are
      limited. Future studies should test whether increased opportunities will increase
      physical activity and impact the increasing overweight problem in youths.

PMID- 17222160
TI  - Assessment of health issues and concerns of Israeli seventh graders during school
      physician examinations: a pilot study.
AB  - BACKGROUND: The AMA Guidelines for Adolescent Preventive Services (GAPS)
      recommends annual medical evaluations during adolescence, emphasizing screening
      and counseling regarding psychosocial issues. In Israel, seventh graders undergo
      medical examinations within the school health services, focusing on the detection
      of physical conditions. We addressed the psychosocial issues of these students by
      introducing an expanded school physician evaluation. METHODS: Twelve school
      physicians performed structured expanded health evaluations for seventh graders
      in 11 schools. Each student completed a questionnaire (checklist) with 22 health
      topics "about which s/he may want to receive information." The physician then
      carried out a biomedical and psychosocial evaluation, physical examination, and
      offered counseling to the student. RESULTS: Two hundred and seventy-eight
      students were examined. The questionnaire required 1-2 minutes, and the
      physician's evaluation 20-25 minutes. Health behaviors revealed included:
      currently dieting (28%), no physical activity after school (35%), ever smoked
      cigarettes (3%), ever smoked a water pipe (9%), used alcoholic beverages (6%),
      and does not always use front (22%) or rear (55%) seat belt. Nine percent rated
      their mood as being less than 7 (on a scale from 1 to 10). The leading topics
      about which the students requested information were height (50%), acne (42%),
      weight (38%), nutrition/diet (37%), physical activity (35%), and menstrual period
      (29% of the girls). The physicians counseled the students on an average of 3.6
      topics per visit. CONCLUSIONS: An expanded school physician examination
      identifies students with psychosocial problems otherwise undetected during
      standard physical examinations, and provides the opportunity to address their
      personal concerns.

PMID- 17222161
TI  - Surveying students about controversial subjects.
AB  - BACKGROUND: Because of school districts' interest in best serving the health
      needs of students, many choose to administer surveys addressing controversial
      topics. Administering such surveys in a voluntary and anonymous manner may help
      reduce conflict. METHODS: This is a review of 2 recent federal court of appeals
      decisions regarding surveying students about controversial topics. RESULTS: The 2
      federal appellate cases examined whether mistakes and misperceptions were made
      when surveying students about controversial topics violated the US Constitution.
      Both courts wrestled with the tension between school and parental authority but
      ultimately ruled in favor of the defendant school district. In Fields v Palmdale
      School District, the Ninth Circuit stated that a parent's right to control a
      child's upbringing does not automatically supersede the school's authority to
      control what goes on during school, including surveying students. In C.N. v
      Ridgewood Board of Education, the Third Circuit decided that a parent's right to
      control a child's upbringing extends into school, but surveying students about
      controversial topics does not violate that right. This article explains the
      significance of these cases and provides 10 suggestions school districts can
      follow to avoid the threat of litigation when surveying students about
      controversial topics. CONCLUSIONS: School districts should ensure a student
      survey relates to the district's overall educational goals. Likewise, the
      district should adequately inform parents of a survey's contents, date of
      administration, and a parent's ability to opt out. Schools should make sure a
      survey is truly voluntary and anonymous. Finally, schools should carefully follow
      local policy and state and federal laws that apply to surveying students, such as
      the federal Protection of Pupil Rights Amendment.

PMID- 17222163
TI  - Membrane transport proteins in health and disease.

PMID- 17222164
TI  - Evidence for airway surface dehydration as the initiating event in CF airway
      disease.
AB  - Cystic fibrosis (CF) lung disease reflects persistent bacterial infection of
      airway lumens. Several hypotheses have been advanced to link mutations in the
      CFTR gene to the failure of the CF lung to defend itself against bacterial
      infection. Amongst the most productive hypotheses at present is the ''low airway
      surface liquid (ASL) volume'' or ''dehydration'' hypothesis. This hypothesis
      predicts that airway surface dehydration produces the mucus adhesion,
      inflammation, and bacterial biofilm formation characteristic of CF. Clinical
      trials of inhaled hypertonic saline have demonstrated therapeutic benefit of
      manoeuvres designed to rehydrate CF airway surfaces.

PMID- 17222165
TI  - Polycystic kidney disease: genes, proteins, animal models, disease mechanisms and
      therapeutic opportunities.
AB  - An increased understanding of the genetic, molecular and cellular mechanisms
      responsible for the development of polycystic kidney disease has laid out the
      foundation for the development of rational therapies. Many animal models where
      these therapies can be tested are currently available. This review summarizes the
      rationale for these treatments, the results of preclinical trials and the
      prospects for clinical trials, some already in early phases of implementation.

PMID- 17222166
TI  - Active sugar transport in health and disease.
AB  - Secondary active glucose transport occurs by at least four members of the SLC5
      gene family. This review considers the structure and function of two premier
      members, SGLT1 and SGLT2, and their role in intestinal glucose absorption and
      renal glucose reabsorption. Genetics disorders of SGLTs include Glucose-Galactose
      Malabsorption, and Familial Renal Glucosuria. SGLT1 plays a central role in Oral
      Rehydration Therapy used so effectively to treat secretory diarrhoea such as
      cholera. Increasing attention is being focused on SGLTs as drug targets for the
      therapy of diabetes.

PMID- 17222167
TI  - New roles for an old enzyme: Na,K-ATPase emerges as an interesting drug target.
AB  - Na,K-ATPase (NKA) is well known for its role as a maintainer of electrolyte and
      fluid balance in cells, organs and whole body. Exciting new findings have
      revealed additional fundamental roles for NKA as a signal transducer and
      modulator of growth, apoptosis, cell adhesion and motility. The signal
      transduction function can be triggered by the binding of ouabain, the mammalian
      analogue of digitalis to NKA. The catalytic subunit of NKA exists in different
      forms and mutations in two of the forms that are expressed in brain can give rise
      to migraine, epilepsy and Parkinsonism-like symptoms. This review will present
      these new aspects of NKA and their clinical implications.

PMID- 17222168
TI  - Regulation and dysregulation of aquaporins in water balance disorders.
AB  - The discovery of aquaporin-1 (AQP1) explained the long-standing biophysical
      question of how water specifically crosses biological membranes. These studies
      led to the identification of a whole new family of membrane proteins, the
      aquaporin water channels. At present, at least eight aquaporins are expressed at
      distinct sites in the kidney and four members of this family (AQP1-4) have been
      demonstrated to play pivotal roles in the physiology and pathophysiology for
      renal regulation of body water balance. In the present review, a number of
      inherited and acquired conditions characterized by urinary concentration defects
      as well as common diseases associated with severe water retention are discussed
      with relation to the role of aquaporins in regulation and dysregulation of renal
      water transport.

PMID- 17222169
TI  - Glomerular filtration rate as measured by serum cystatin C is an important
      determinant of plasma homocysteine and serum methylmalonic acid in the elderly.
AB  - OBJECTIVES: To explore the dependence of glomerular filtration rate (GFR) on
      plasma total homocysteine (tHcy) and serum methylmalonic acid (MMA), as well as
      the consequences for the diagnosis of cobalamin and/or folic acid deficiency in
      an elderly community-dwelling population. DESIGN AND SETTING: Population-based
      study of 209 community-dwelling subjects, mean age 76 years. INTERVENTIONS: Four
      months' treatment study with oral vitamin B(12), folic acid and B(6) or placebo.
      MAIN OUTCOME MEASURES: Determinants of tHcy and MMA: cystatin C as a marker of
      GFR and serum/plasma concentrations of vitamin B(12) and folate, age and sex.
      RESULTS: Elevated cystatin C (>1.55 mg L(-1)) was found in 31.3% (men) and 13.0%
      (women). Elevated tHcy (> or = 16 micromol L(-1)) occurred in 53% and elevated
      MMA (> or = 0.34 micromol L(-1)) in 11% of all subjects. When GFR was taken into
      consideration, the proportion of elevated tHcy was reduced to 10% (20/209),
      whilst the proportion of elevated MMA was unchanged. Cystatin C was correlated
      with tHcy (r = 0.45, P < 0.001) and with MMA (r =0.28, P < 0.001), independently
      of vitamin B(12)- and folate status. According to multiple regression,
      independent predictors for tHcy were plasma folate (15%), cystatin C (11%) and
      vitamin B(12) (4%), and for MMA, cystatin C (8%) and vitamin B(12) (2%).
      CONCLUSIONS: The prevalence of elevated tHcy may be overestimated in elderly
      populations unless GFR is taken into account. Nomograms for evaluation of tHcy
      and MMA in relation to both cystatin C and serum creatinine are presented.

PMID- 17222170
TI  - The association between the proximal extension of the clot and the severity of
      pulmonary embolism (PE): a proposal for a new radiological score for PE.
AB  - BACKGROUND: The aim of the study was to investigate the association between the
      proximal level of the clot and the severity of pulmonary embolism (PE). METHODS:
      The cohort consisted of 99 consecutive patients with PE diagnosed by multi
      detector computed tomography. A new score was constructed by calculating the mean
      value of the largest affected vessel [sub-segmental = 1, segmental = 2, lobar =
      3, main pulmonary artery (MPA) = 4] in each lung. RESULTS: A significant
      association was found between the most proximal level of PE and pulmonary artery
      obstruction index (PAOI) (P < 0.0001), right ventricular (RV)/left ventricular
      (LV) ratio (P < 0.0001), and PaO(2) (P = 0.004). No significant association was
      found between systolic blood pressure and the level of PE. Troponin-T was
      elevated in none of the sub-segmental, 5% of segmental, 20% of lobar, and in 56%
      of PEs in the MPA (P = 0.001). Significant association was found between the
      proposed score and PAOI (P < 0.0001), RV/LV ratio (P < 0.0001), PaO(2) (P <
      0.008). Troponin-T was elevated in 10% of level 1, 0% of level 2, 43% level of 3,
      66% of level 4 PE (P < 0.0001). Cut-off level score 4 yielded a sensitivity of
      84% and a specificity of 74% for the detection of elevated troponin-T.
      CONCLUSIONS: In conclusion, the study indicates that both the most proximal level
      of PE and the proposed score are related to the severity of PE as determined by
      blood oxygenation, biochemical and radiological parameters and could therefore be
      of value for rapid risk stratification of PE. However, the prognostic value of
      these classifications and their clinical significance needs to be evaluated in
      properly designed studies.

PMID- 17222171
TI  - Haemorheological, platelet and endothelial indices in relation to global measures
      of cardiovascular risk in hypertensive patients: a substudy of the Anglo
      Scandinavian Cardiac Outcomes Trial.
AB  - INTRODUCTION AND METHODS: We tested the hypothesis that there was a significant
      relationship between haemorheological markers [white blood cell count (WCC),
      plasma viscosity (PV), haematocrit (HCT) and fibrinogen], as well as plasma von
      Willebrand factor (vWf, an index of endothelial damage/dysfunction) and soluble P
      selectin (sP-sel, an index of platelet activation), to five global measures of
      cardiovascular risk [i.e. Framingham coronary heart disease (CHD), stroke and
      cardiovascular death score, the Pocock cardiovascular risk score and the sum of
      individual risk factors]. RESULTS: Men with a high (> or = median, n = 156)
      Framingham 10-year CHD risk score had higher levels of WBC (P = 0.027),
      fibrinogen (P = 0.012) and vWF (P = 0.002) than 153 men with results < median.
      Men with a high 10-year stroke risk score had significantly higher levels of
      fibrinogen (P = 0.01) and vWF (P < 0.0001). In stepwise linear regression
      analysis in men, vWF and fibrinogen were independent predictors of the number of
      risk factors (P < 0.0001), whilst WCC, vWF and fibrinogen emerged as independent
      predictors of Framingham CHD risk (P < 0.0001), and fibrinogen and vWF predicted
      Framingham stroke risk (R(2) = 0.089, P < 0.0001). vWF, PV and fibrinogen were
      predictors of Pocock cardiovascular death risk (P < 0.0001) but vWF was the only
      independent predictor of Framingham cardiovascular death risk (P = 0.001).
      CONCLUSIONS: Abnormal haemorheological factors (particularly high plasma
      fibrinogen levels) and endothelial damage/dysfunction (high vWF), but not
      platelet activation (sP-sel), are related to established cardiovascular and death
      risk scores. This relationship was most evident amongst male 'high-risk'
      hypertensive subjects.

PMID- 17222172
TI  - Extraintestinal focal infections in adults with nontyphoid Salmonella
      bacteraemia: predisposing factors and clinical outcome.
AB  - BACKGROUND: Nontyphoid Salmonella (NTS) isolates lead to not only self-limited,
      acute gastrointestinal infections, but also bacteraemia with or without
      extraintestinal focal infections (EFIs). The risk factors associated with EFIs in
      adults with NTS bacteraemia were not clearly elucidated. METHODS: In a medical
      center in southern Taiwan, patients aged > or = 18 years with NTS bacteraemia
      between January 1999 and June 2005 were included for analysis. RESULTS: Of 129
      patients, 51 (39.5%) were complicated with EFIs. The most common EFI was mycotic
      aneurysm, followed by pleuropulmonary infections and spinal osteomyelitis.
      Compared to patients with primary bacteraemia, those with EFIs had higher
      leucocyte counts (P = 0.004) and higher serum levels of C-reactive protein (P <
      0.0001). The development of EFIs was associated with a higher mortality, more
      severe septic manifestations, longer hospital stays and duration of antimicrobial
      therapy. Univariate analysis revealed that diabetes mellitus (P = 0.02),
      hypertension (P = 0.02) and chronic lung disease (P = 0.006) were significantly
      associated with EFIs. However, patients with malignancy (P = 0.01) and
      immunosuppressive therapy (P = 0.03) were less likely to develop EFIs. On the
      basis of multivariate analysis, an independent factor for the occurrence of EFIs
      was age [adjusted odds ratio (aOR) 1.05; 95% confidence interval (CI) 1.02-1.07;
      P < 0.0001], whilst malignancy was negatively associated with EFIs (aOR 0.16; 95%
      CI 0.14-0.78; P = 0.01). CONCLUSION: Amongst patients with NTS bacteraemia, EFIs
      often occurred in the aged, and were associated with a higher mortality and
      morbidity. Recognition of specific host factors is essential for identification
      of EFIs which often demand early surgical interventions and prolonged
      antimicrobial therapy.

PMID- 17222173
TI  - Osteonecrosis of the jaws: maxillofacial recommendations for bisphosphonate
      prescribers.

PMID- 17222174
TI  - Vitamin C. Biosynthesis, recycling and degradation in mammals.
AB  - Vitamin C, a reducing agent and antioxidant, is a cofactor in reactions catalyzed
      by Cu(+)-dependent monooxygenases and Fe(2+)-dependent dioxygenases. It is
      synthesized, in vertebrates having this capacity, from d-glucuronate. The latter
      is formed through direct hydrolysis of uridine diphosphate (UDP)-glucuronate by
      enzyme(s) bound to the endoplasmic reticulum membrane, sharing many properties
      with, and most likely identical to, UDP-glucuronosyltransferases. Non
      glucuronidable xenobiotics (aminopyrine, metyrapone, chloretone and others)
      stimulate the enzymatic hydrolysis of UDP-glucuronate, accounting for their
      effect to increase vitamin C formation in vivo. Glucuronate is converted to l
      gulonate by aldehyde reductase, an enzyme of the aldo-keto reductase superfamily.
      l-Gulonate is converted to l-gulonolactone by a lactonase identified as SMP30 or
      regucalcin, whose absence in mice leads to vitamin C deficiency. The last step in
      the pathway of vitamin C synthesis is the oxidation of l-gulonolactone to l
      ascorbic acid by l-gulonolactone oxidase, an enzyme associated with the
      endoplasmic reticulum membrane and deficient in man, guinea pig and other species
      due to mutations in its gene. Another fate of glucuronate is its conversion to d
      xylulose in a five-step pathway, the pentose pathway, involving identified
      oxidoreductases and an unknown decarboxylase. Semidehydroascorbate, a major
      oxidation product of vitamin C, is reconverted to ascorbate in the cytosol by
      cytochrome b(5) reductase and thioredoxin reductase in reactions involving NADH
      and NADPH, respectively. Transmembrane electron transfer systems using ascorbate
      or NADH as electron donors serve to reduce semidehydroascorbate present in
      neuroendocrine secretory vesicles and in the extracellular medium.
      Dehydroascorbate, the fully oxidized form of vitamin C, is reduced spontaneously
      by glutathione, as well as enzymatically in reactions using glutathione or NADPH.
      The degradation of vitamin C in mammals is initiated by the hydrolysis of
      dehydroascorbate to 2,3-diketo-l-gulonate, which is spontaneously degraded to
      oxalate, CO(2) and l-erythrulose. This is at variance with bacteria such as
      Escherichia coli, which have enzymatic degradation pathways for ascorbate and
      probably also dehydroascorbate.

PMID- 17222175
TI  - Cold stress defense in the freshwater sponge Lubomirskia baicalensis. Role of
      okadaic acid produced by symbiotic dinoflagellates.
AB  - The endemic freshwater sponge Lubomirskia baicalensis lives in Lake Baikal in
      winter (samples from March have been studied) under complete ice cover at near 0
      degrees C, and in summer in open water at 17 degrees C (September). In March,
      specimens show high metabolic activity as reflected by the production of gametes.
      L. baicalensis lives in symbiosis with green dinoflagellates, which are related
      to Gymnodinium sanguineum. Here we show that these dinoflagellates produce the
      toxin okadaic acid (OA), which is present as a free molecule as well as in a
      protein-bound state. In metazoans OA inhibits both protein phosphatase-2A and
      protein phosphatase-1 (PP1). Only cDNA corresponding to PP1 could be identified
      in L. baicalensis and subsequently isolated from a L. baicalensis cDNA library.
      The deduced polypeptide has a molecular mass of 36 802 Da and shares the
      characteristic domains known from other protein phosphatases. As determined by
      western blot analysis, the relative amount of PP1 is almost the same in March
      (under ice) and September (summer). PP1 is not inhibited by low OA concentrations
      (100 nm); concentrations above 300 nm are required for inhibition. A sponge cell
      culture system (primmorphs) was used to show that at low temperatures (4 degrees
      C) expression of hsp70 is strongly induced and hsp70 synthesis is augmented after
      incubation with 100 nm OA to levels measured at 17 degrees C. In the enriched
      extract, PP1 activity at 4 degrees C is close to that measured at 17 degrees C.
      Immunoabsorption experiments revealed that hsp70 contributes to the high protein
      phosphatase activity at 4 degrees C. From these data we conclude that the toxin
      OA is required for the expression of hsp70 at low temperature, and therefore
      contributes to the cold resistance of the sponge.

PMID- 17222176
TI  - High-resolution NMR studies of the zinc-binding site of the Alzheimer's amyloid
      beta-peptide.
AB  - Metal binding to the amyloid beta-peptide is suggested to be involved in the
      pathogenesis of Alzheimer's disease. We used high-resolution NMR to study zinc
      binding to amyloid beta-peptide 1-40 at physiologic pH. Metal binding induces a
      structural change in the peptide, which is in chemical exchange on an
      intermediate rate, between the apo-form and the holo-form, with respect to the
      NMR timescale. This causes loss of NMR signals in the resonances affected by the
      binding. Heteronuclear correlation experiments, (15)N-relaxation and amide proton
      exchange experiments on amyloid beta-peptide 1-40 revealed that zinc binding
      involves the three histidines (residues 6, 13 and 14) and the N-terminus, similar
      to a previously proposed copper-binding site [Syme CD, Nadal RC, Rigby SE, Viles
      JH (2004) J Biol Chem 279, 18169-18177]. Fluorescence experiments show that zinc
      shares a common binding site with copper and that the metals have similar
      affinities for amyloid beta-peptide. The dissociation constant K(d) of zinc for
      the fragment amyloid beta-peptide 1-28 was measured by fluorescence, using
      competitive binding studies, and that for amyloid beta-peptide 1-40 was measured
      by NMR. Both methods gave K(d) values in the micromolar range at pH 7.2 and 286
      K. Zinc also has a second, weaker binding site involving residues between 23 and
      28. At high metal ion concentrations, the metal-induced aggregation should mainly
      have an electrostatic origin from decreased repulsion between peptides. At low
      metal ion concentrations, on the other hand, the metal-induced structure of the
      peptide counteracts aggregation.

PMID- 17222177
TI  - Ascorbic acid-pretreated quartz enhances cyclo-oxygenase-2 expression in RAW
      264.7 murine macrophages.
AB  - Exposure to quartz particles induces a pathological process named silicosis.
      Alveolar macrophages initiate the disease through their activation, which is the
      origin of the later dysfunctions. Ascorbic acid is known to selectively dissolve
      the quartz surface. During the reaction, ascorbic acid progressively disappears
      and hydroxyl radicals are generated from the quartz surface. These observations
      may be relevant to mammalian quartz toxicity, as substantial amounts of ascorbic
      acid are present in the lung epithelium. We studied the inflammatory response of
      the murine macrophage cell line RAW 264.7 incubated with ascorbic acid-treated
      quartz, through the expression and activity of the enzyme cyclo-oxygenase-2 (COX
      2). COX-2 expression and prostaglandin secretion were enhanced in cells incubated
      with ascorbic acid-treated quartz. In contrast, no changes were observed in cells
      incubated with Aerosil OX50, an amorphous form of silica. Quantification of COX-2
      mRNA showed a threefold increase in cells incubated with ascorbic acid-treated
      quartz compared with controls. The transcription factors, NF-kappaB, pCREB and AP
      1, were all implicated in the increased inflammatory response. Reactive oxygen
      species (H(2)O(2) and OH(*)) were involved in COX-2 expression in this
      experimental model. Parallel experiments performed on rat alveolar macrophages
      from bronchoalveolar lavage confirmed the enhanced COX-2 expression and activity
      in the cells incubated with ascorbic acid-treated quartz compared with untreated
      quartz. In conclusion, the selective interaction with, and modification of,
      quartz particles by ascorbic acid may be a crucial event determining the
      inflammatory response of macrophages, which may subsequently develop into acute
      inflammation, eventually leading to the chronic pulmonary disease silicosis.

PMID- 17222178
TI  - Impact of alterations near the [NiFe] active site on the function of the H(2)
      sensor from Ralstonia eutropha.
AB  - In proteobacteria capable of H(2) oxidation under (micro)aerobic conditions,
      hydrogenase gene expression is often controlled in response to the availability
      of H(2). The H(2)-sensing signal transduction pathway consists of a heterodimeric
      regulatory [NiFe]-hydrogenase (RH), a histidine protein kinase and a response
      regulator. To gain insights into the signal transmission from the Ni-Fe active
      site in the RH to the histidine protein kinase, conserved amino acid residues in
      the L0 motif near the active site of the RH large subunit of Ralstonia eutropha
      H16 were exchanged. Replacement of the strictly conserved Glu13 (E13N, E13L)
      resulted in loss of the regulatory, H(2)-oxidizing and D(2)/H(+) exchange
      activities of the RH. According to EPR and FTIR analysis, these RH derivatives
      contained fully assembled [NiFe] active sites, and para-/ortho-H(2) conversion
      activity showed that these centres were still able to bind H(2). This indicates
      that H(2) binding at the active site is not sufficient for the regulatory
      function of H(2) sensors. Replacement of His15, a residue unique in RHs, by Asp
      restored the consensus of energy-linked [NiFe]-hydrogenases. The respective RH
      mutant protein showed only traces of H(2)-oxidizing activity, whereas its
      D(2)/H(+)-exchange activity and H(2)-sensing function were almost unaffected.
      H(2)-dependent signal transduction in this mutant was less sensitive to oxygen
      than in the wild-type strain. These results suggest that H(2) turnover is not
      crucial for H(2) sensing. It may even be detrimental for the function of the H(2)
      sensor under high O(2) concentrations.

PMID- 17222179
TI  - Leishmania donovani bisubunit topoisomerase I gene fusion leads to an active
      enzyme with conserved type IB enzyme function.
AB  - All eukaryotic topoisomerase I enzymes are monomeric enzymes, whereas the
      kinetoplastid family (Trypanosoma and Leishmania) possess an unusual bisubunit
      topoisomerase I. To determine what happens to the enzyme architecture and
      catalytic property if the two subunits are fused, and to explore the functional
      relationship between the two subunits, we describe here in vitro gene fusion of
      Leishmania bisubunit topoisomerase I into a single ORF encoding a new monomeric
      topoisomerase I (LdTOPIL-fus-S). It was found that LdTOPIL-fus-S is active. Gene
      fusion leads to a significant modulation of in vitro topoisomerase I activity
      compared to the wild-type heterodimeric enzyme (LdTOPILS). Interestingly, an N
      terminal truncation mutant (1-210 amino acids) of the small subunit, when fused
      to the intact large subunit [LdTOPIL-fus-Delta(1-210)S], showed reduced
      topoisomerase I activity and camptothecin sensitivity in comparison to LdTOPIL
      fus-S. Investigation of the reduction in enzyme activity indicated that the
      nonconserved 1-210 residues of LdTOPIS probably act as a 'pseudolinker' domain
      between the core and catalytic domain of the fused Leishmania enzyme, whereas
      mutational analysis of conserved His453 in the core DNA-binding domain (LdTOPIL)
      strongly suggested that its role is to stabilize the enzyme-DNA transition state
      through hydrogen bonding to one of the nonbridging oxygens. Taken together, our
      findings provide an insight into the details of the unusual structure of
      bisubunit topoisomerase I of Leishmania donovani.

PMID- 17222181
TI  - Modular metabolic control analysis of large responses.
AB  - Deciphering the laws that govern metabolic responses of complex systems is
      essential to understand physiological functioning, pathological conditions and
      the outcome of experimental manipulations of intact cells. To this aim, a
      theoretical and experimental sensitivity analysis, called modular metabolic
      control analysis (MMCA), was proposed. This field was previously developed under
      the assumptions of infinitesimal changes and/or proportionality between
      parameters and rates, which are usually not fulfilled in vivo. Here we develop a
      general MMCA for two modules, not relying on those assumptions. Control
      coefficients and elasticity coefficients for large changes are defined. These are
      subject to constraints: summation and response theorems, and relationships that
      allow calculating control from elasticity coefficients. We show how to determine
      the coefficients from top-down experiments, measuring the rates of the isolated
      modules as a function of the linking intermediate (there is no need to change
      parameters inside the modules). The novel formalism is applied to data of two
      experimental studies from the literature. In one of these, 40% increase in the
      activity of the supply module results in less than 4% increase in flux, while
      infinitesimal MMCA predicts more than 30% increase in flux. In addition, it is
      not possible to increase the flux by manipulating the activity of demand. The
      impossibility of increasing the flux by changing the activity of a single module
      is due to an abrupt decrease of the control of the modules when their
      corresponding activities are increased. In these cases, the infinitesimal
      approach can give highly erroneous predictions.

PMID- 17222180
TI  - Phosphatidylserine induces functional and structural alterations of the membrane
      associated pleckstrin homology domain of phospholipase C-delta1.
AB  - The membrane binding affinity of the pleckstrin homology (PH) domain of
      phospholipase C (PLC)-delta1 was investigated using a vesicle coprecipitation
      assay and the structure of the membrane-associated PH domain was probed using
      solid-state (13)C NMR spectroscopy. Twenty per cent phosphatidylserine (PS) in
      the membrane caused a moderate but significant reduction of the membrane binding
      affinity of the PH domain despite the predicted electrostatic attraction between
      the PH domain and the head groups of PS. Solid-state NMR spectra of the PH domain
      bound to the phosphatidylcholine (PC)/PS/phosphatidylinositol 4,5-bisphosphate
      (PIP(2)) (75 : 20 : 5) vesicle indicated loss of the interaction between the
      amphipathic alpha2-helix of the PH domain and the interface region of the
      membrane which was previously reported for the PH domain bound to PC/PIP(2) (95 :
      5) vesicles. Characteristic local conformations in the vicinity of Ala88 and
      Ala112 induced by the hydrophobic interaction between the alpha2-helix and the
      membrane interface were lost in the structure of the PH domain at the surface of
      the PC/PS/PIP(2) vesicle, and consequently the structure becomes identical to the
      solution structure of the PH domain bound to d-myo-inositol 1,4,5-trisphosphate.
      These local structural changes reduce the membrane binding affinity of the PH
      domain. The effects of PS on the PH domain were reversed by NaCl and MgCl(2),
      suggesting that the effects are caused by electrostatic interaction between the
      protein and PS. These results generally suggest that the structure and function
      relationships among PLCs and other peripheral membrane proteins that have similar
      PH domains would be affected by the local lipid composition of membranes.

PMID- 17222182
TI  - Two splicing isoforms of the Y-box protein ctYB-1 appear on the same mRNA
      molecule.
AB  - Y-box proteins constitute an evolutionarily conserved family of DNA- and RNA
      binding proteins involved in the regulation of transcription and translation. In
      the dipteran Chironomus tentans, a homologue to the vertebrate Y-box protein YB-1
      was recently characterized and designated ctYB-1. It is transferred from nucleus
      to cytoplasm bound to mRNA and is likely to affect translation. It appears in two
      size variants, p40 and p50. We further analysed the two size variants and their
      interaction with mRNA. Southern blot analysis, in situ hybridization and RT-PCR
      analysis suggested that there is just one YB-1 gene, and that the two size
      variants represent splicing isoforms. In a C. tentans epithelial cell line, only
      p40 is present, whereas both variants appear together in eight tissues from
      fourth-instar larvae, although in somewhat different proportions. Furthermore,
      the appearance of the two isoforms was studied in relation to a specific 35-40 kb
      mRNA transcript in the salivary glands, the Balbiani ring mRNA. Because of their
      exceptional size, Balbiani ring messenger ribonucleoprotein particles in
      nucleoplasm and Balbiani ring polysomes in cytoplasm could be identified and
      selectively studied. We were able to establish that both isoforms are associated
      with both nuclear and cytoplasmic Balbiani ring mRNA. In addition, a p50-specific
      antibody coimmunoprecipitated p40 from Balbiani ring polysomes, suggesting that
      the two splicing isoforms are located along the same Balbiani ring mRNA molecule.
      The functional significance of the two isoforms is being discussed.

PMID- 17222183
TI  - Induction of uPA gene expression by the blockage of E-cadherin via Src- and Shc
      dependent Erk signaling.
AB  - Loss of E-cadherin-mediated cell-cell adhesion and expression of proteolytic
      enzymes characterize the transition from benign lesions to invasive, metastatic
      tumor, a rate-limiting step in the progression from adenoma to carcinoma in vivo.
      A soluble E-cadherin fragment found recently in the serum and urine of cancer
      patients has been shown to disrupt cell-cell adhesion and to drive cell invasion
      in a dominant-interfering manner. Physical disruption of cell-cell adhesion can
      be mimicked by the function-blocking antibody Decma. We have shown previously in
      MCF7 and T47D cells that urokinase-type plasminogen activator (uPA) activity is
      up-regulated upon disruption of E-cadherin-dependent cell-cell adhesion. We
      explored the underlying molecular mechanisms and found that blockage of E
      cadherin by Decma elicits a signaling pathway downstream of E-cadherin that leads
      to Src-dependent Shc and extracellular regulated kinase (Erk) activation and
      results in uPAgene activation. siRNA-mediated knockdown of endogenous Src
      homology collagen protein (Shc) and subsequent expression of single Shc isoforms
      revealed that p46(Shc) and p52(Shc) but not p66(Shc) were able to mediate Erk
      activation. A parallel pathway involving PI3K contributed partially to Decma
      induced Erk activation. This report describes that disruption of E-cadherin
      dependent cell-cell adhesion induces intracellular signaling with the potential
      to enhance tumorigenesis and, thus, offers new insights into the
      pathophysiological mechanisms of tumor development.

PMID- 17222184
TI  - Thermodynamic characterization of interleukin-8 monomer binding to CXCR1 receptor
      N-terminal domain.
AB  - Chemokines elicit their function by binding receptors of the G-protein-coupled
      receptor class, and the N-terminal domain (N-domain) of the receptor is one of
      the two critical ligand-binding sites. In this study, the thermodynamic basis for
      binding of the chemokine interleukin-8 (IL-8) to the N-domain of its receptor
      CXCR1 was characterized using isothermal titration calorimetry. We have shown
      previously that only the monomer of IL-8, and not the dimer, functions as a high
      affinity ligand, so in this study we used the IL-8(1-66) deletion mutant which
      exists as a monomer. Calorimetry data indicate that the binding is enthalpically
      favored and entropically disfavored, and a negative heat capacity change
      indicates burial of hydrophobic residues in the complex. A characteristic feature
      of chemokine receptor N-domains is the large number of acidic residues, and
      experiments using different buffers show no net proton transfer, indicating that
      the CXCR1 N-domain acidic residues are not protonated in the binding process.
      CXCR1 N-domain peptide is unstructured in the free form but adopts a more defined
      structure in the bound form, and so binding is coupled to induction of the
      structure of the N-domain. Measurements in the presence of the osmolyte,
      trimethylamine N-oxide, which induces the structure of unfolded proteins, show
      that formation of the coupled N-domain structure involves only small DeltaH and
      DeltaS changes. These results together indicate that the binding is driven by
      packing interactions in the complex that are enthalpically favored, and are
      consistent with the observation that the N-domain binds in an extended form and
      interacts with multiple IL-8 N-loop residues over a large surface area.

PMID- 17222185
TI  - Comparative studies of endonuclease I from cold-adapted Vibrio salmonicida and
      mesophilic Vibrio cholerae.
AB  - Endonuclease I is a periplasmic or extracellular enzyme present in many different
      Proteobacteria. The endA gene encoding endonuclease I from the psychrophilic and
      mildly halophilic bacterium Vibrio salmonicida and from the mesophilic brackish
      water bacterium Vibrio cholerae have been cloned, over-expressed in Escherichia
      coli, and purified. A comparison of the enzymatic properties shows large
      differences in NaCl requirements, optimum pH, temperature stability and catalytic
      efficiency of the two proteins. The V. salmonicida EndA shows typical cold
      adapted features such as lower unfolding temperature, lower temperature optimum
      for activity, and higher specific activity than V. cholerae EndA. The
      thermodynamic activation parameters confirm the psychrophilic nature of V.
      salmonicida EndA with a much lower activation enthalpy. The optimal conditions
      for enzymatic activity coincide well with the corresponding optimal requirements
      for growth of the organisms, and the enzymes function predominantly as DNases at
      physiological concentrations of NaCl. The periplasmic or extracellular
      localization of the enzymes, which renders them constantly exposed to the outer
      environment of the cell, may explain this fine-tuning of biochemical properties.

PMID- 17222186
TI  - Elongation of polyunsaturated fatty acids in trypanosomatids.
AB  - Leishmania major synthesizes polyunsaturated fatty acids by using Delta6, Delta5
      and Delta4 front-end desaturases, which have recently been characterized [Tripodi
      KE, Buttigliero LV, Altabe SG & Uttaro AD (2006) FEBS J273, 271-280], and two
      predicted elongases specific for C18 Delta6 and C20 Delta5 polyunsaturated fatty
      acids, respectively. Trypanosoma brucei and Trypanosoma cruzi lack Delta6 and
      Delta5 desaturases but contain Delta4 desaturases, implying that trypanosomes use
      exogenous polyunsaturated fatty acids to produce C22 Delta4 fatty acids. In order
      to identify putative precursors of these C22 fatty acids and to completely
      describe the pathways for polyunsaturated fatty acid biosynthesis in
      trypanosomatids, we have performed a search in the three genomes and identified
      four different elongase genes in T. brucei, five in T. cruzi and 14 in L. major.
      After a phylogenetic analysis of the encoded proteins together with elongases
      from a variety of other organisms, we selected four candidate polyunsaturated
      fatty acid elongases. Leishmania major CAJ02037, T. brucei AAX69821 and T. cruzi
      XP_808770 share 57-52% identity, and group together with C20 Delta5
      polyunsaturated fatty acid elongases from algae. The predicted activity was
      corroborated by functional characterization after expression in yeast. T. brucei
      elongase was also able to elongate Delta8 and Delta11 C20 polyunsaturated fatty
      acids. L. major CAJ08636, which shares 33% identity with Mortierella alpinaDelta6
      elongase, showed a high specificity for C18 Delta6 polyunsaturated fatty acids.
      In all cases, a preference for n6 polyunsaturated fatty acids was observed. This
      indicates that L. major has, as predicted, Delta6 and Delta5 elongases and a
      complete pathway for polyunsaturated fatty acid biosynthesis. Trypanosomes
      contain only Delta5 elongases, which, together with Delta4 desaturases, allow
      them to use eicosapentaenoic acid and arachidonic acid, a precursor that is
      relatively abundant in the host, for C22 polyunsaturated fatty acid biosynthesis.

PMID- 17222187
TI  - Crystal structures of a bacterial 6-phosphogluconate dehydrogenase reveal aspects
      of specificity, mechanism and mode of inhibition by analogues of high-energy
      reaction intermediates.
AB  - Crystal structures of recombinant Lactococcus lactis 6-phosphogluconate
      dehydrogenase (LlPDH) in complex with substrate, cofactor, product and inhibitors
      have been determined. LlPDH shares significant sequence identity with the enzymes
      from sheep liver and the protozoan parasite Trypanosoma brucei for which
      structures have been reported. Comparisons indicate that the key residues in the
      active site are highly conserved, as are the interactions with the cofactor and
      the product ribulose 5-phosphate. However, there are differences in the
      conformation of the substrate 6-phosphogluconate which may reflect distinct
      states relevant to catalysis. Analysis of the complex formed with the potent
      inhibitor 4-phospho-d-erythronohydroxamic acid, suggests that this molecule does
      indeed mimic the high-energy intermediate state that it was designed to. The
      analysis also identified, as a contaminant by-product of the inhibitor synthesis,
      4-phospho-d-erythronamide, which binds in similar fashion. LlPDH can now serve as
      a model system for structure-based inhibitor design targeting the enzyme from
      Trypanosoma species.

PMID- 17222188
TI  - Inhibition of cobalamin-dependent methionine synthase by substituted benzo-fused
      heterocycles.
AB  - The cobalamin-dependent cytosolic enzyme, methionine synthase (EC.2.1.1.13),
      catalyzes the remethylation of homocysteine to methionine using 5
      methyltetrahydrofolate as the methyl donor. The products of this remethylation-
      methionine and tetrahydrofolate--participate in the active methionine and folate
      pathways. Impaired methionine synthase activity has been implicated in the
      pathogenesis of anaemias, cancer and neurological disorders. Although the need
      for potent and specific inhibitors of methionine synthase has been recognized,
      there is a lack of such agents. In this study, we designed, synthesized and
      evaluated the inhibitory activity of a series of substituted benzimidazoles and
      small benzothiadiazoles. Kinetic analysis revealed that the benzimidazoles act as
      competitive inhibitors of the rat liver methionine synthase, whilst the most
      active benzothiadiazole (IC(50) = 80 microm) exhibited characteristics of
      uncompetitive inhibition. A model of the methyltetrahydrofolate-binding site of
      the rat liver methionine synthase was constructed; docking experiments were
      designed to elucidate, in greater detail, the binding mode and reveal structural
      requirements for the design of inhibitors of methionine synthase. Our results
      indicate that the potency of the tested compounds is related to a planar region
      of the inhibitor that can be positioned in the centre of the active site, the
      presence of a nitro functional group and two or three probable hydrogen-bonding
      interactions.

PMID- 17222189
TI  - Biological systems of the host cell involved in Agrobacterium infection.
AB  - Genetic transformation of plants by Agrobacterium, which in nature causes
      neoplastic growths, represents the only known case of trans-kingdom DNA transfer.
      Furthermore, under laboratory conditions, Agrobacterium can also transform a wide
      range of other eukaryotic species, from fungi to sea urchins to human cells. How
      can the Agrobacterium virulence machinery function in such a variety of
      evolutionarily distant and diverse species? The answer to this question lies in
      the ability of Agrobacterium to hijack fundamental cellular processes which are
      shared by most eukaryotic organisms. Our knowledge of these host cellular
      functions is critical for understanding the molecular mechanisms that underlie
      genetic transformation of eukaryotic cells. This review outlines the bacterial
      virulence machinery and provides a detailed discussion of seven major biological
      systems of the host cell-cell surface receptor arrays, cellular motors, nuclear
      import, chromatin targeting, targeted proteolysis, DNA repair, and plant immunity
      -thought to participate in the Agrobacterium-mediated genetic transformation.

PMID- 17222191
TI  - Differential function of Listeria monocytogenes listeriolysin O and
      phospholipases C in vacuolar dissolution following cell-to-cell spread.
AB  - We investigated the role of listeriolysin O (LLO) and the bacterial
      phospholipases PI-PLC and PC-PLC in cell-to-cell spread of Listeria
      monocytogenes. We showed that LLO is essential for cell-to-cell spread in primary
      murine macrophages. Electron micrographs revealed that in the absence of
      continued LLO expression, bacteria remain trapped in secondary spreading vacuoles
      having either a double or single membrane. In bacteria lacking PI-PLC and PC-PLC,
      cessation of LLO expression after initiation of infection resulted in a
      significant increase in the proportion of bacteria trapped in double-membrane
      compartments. We propose that the bacterial phospholipases are involved in the
      dissolution of the inner membrane of the spreading vacuole, yet are not
      sufficient for disruption of the outer membrane. As a consequence, we identified
      LLO as a key factor in the disruption of the outer membrane. This model is
      consistent with the observation that LLO is dispensable for cell-to-cell spread
      from human macrophages into a cell type in which LLO is not required for vacuolar
      escape. These data suggest that during human infection, spreading of L.
      monocytogenes to distant organs is likely to occur even in the absence of LLO
      expression, and that the bacterial phospholipases may be sufficient to mediate
      continued cell-to-cell spread.

PMID- 17222190
TI  - FimH-mediated Escherichia coli K1 invasion of human brain microvascular
      endothelial cells.
AB  - Adhesion to brain microvascular endothelial cells, which constitute the blood
      brain barrier is considered important in Escherichia coli K1 bacterial
      penetration into the central nervous system. Type 1 fimbriae are known to mediate
      bacterial interactions with human brain microvascular endothelial cells (HBMEC).
      Here, we demonstrate that type 1 fimbriae, specifically FimH adhesin is not only
      an adhesive organelle that provides bacteria with a foothold on brain endothelial
      cells but also triggers signalling events that promote E. coli K1 invasion in
      HBMEC. This is shown by our demonstrations that exogenous FimH increases
      cytosolic-free-calcium levels as well as activates RhoA. Using purified
      recombinant mannose-recognition domain of FimH, we identified a
      glycosylphosphatidylinositol-anchored receptor, CD48, as a putative HBMEC
      receptor for FimH. Furthermore, E. coli K1 binding to and invasion of HBMEC were
      blocked by CD48 antibody. Taken together, these findings indicate that FimH
      induces host cell signalling cascades that are involved in E. coli K1 invasion of
      HBMEC and CD48 is a putative HBMEC receptor for FimH.

PMID- 17222192
TI  - A broad antiviral neutral glycolipid, fattiviracin FV-8, is a membrane fluidity
      modulator.
AB  - To screen for an effective antiviral compound which acts as a membrane fluidity
      modulator, dichotomous effects on human immunodeficiency virus type 1 (HIV-1)
      infection due to different treatments of several glycolipids and lipids were
      examined. Continuous treatment of infected cells with 40 microg ml(-1)
      fattiviracin FV-8, a neutral glycolipid isolated from Streptomycetes, inhibited
      HIV-1 infection by 96%, whereas pretreatment with 400 microg ml(-1) enhanced
      infectivity 4.7-fold. The glycolipid showed similar effects as glycyrrhizin; it
      inhibited infection by broad enveloped viruses, blocked cell-cell fusion, reduced
      the infectivity of treated virions and enhanced susceptibility to viral infection
      and cell-cell fusion of cells pretreated with high doses of the compound.
      Suppression and enhancement was correlated with decreased and increased fluidity
      of plasma membrane of the fattiviracin FV-8-treated cells. Restricted movement of
      membrane molecules might impede the formation of a wide fusion pore, and
      therefore be critical to the entry of viruses. Thus, this can be applied as a new
      strategy to inhibit viral infections.

PMID- 17222193
TI  - Systemic mastocytosis simulating osseous metastatic disease.

PMID- 17222194
TI  - Porphyria cutanea tarda complicating transfusion-dependent myelodysplastic
      syndrome.

PMID- 17222195
TI  - PGK deficiency.
AB  - Phosphoglycerate kinase (PGK) deficiency is one of the relatively uncommon causes
      of hereditary non-spherocytic haemolytic anaemia (HNSHA). The gene encoding the
      erythrocyte enzyme PGK1, is X-linked. Mutations of this gene may cause chronic
      haemolysis with or without mental retardation and they may cause myopathies,
      often with episodes of myoglobinuria, or a combination of these clinical
      manifestations. Twenty-six families have been described and in 20 of these the
      mutations are known. The reason for different clinical manifestations of
      mutations of the same gene remains unknown.

PMID- 17222196
TI  - Mechanisms of action of immune tolerance induction against factor VIII in
      patients with congenital haemophilia A and factor VIII inhibitors.
AB  - In its most severe form, haemophilia A is a life-threatening haemorrhagic
      bleeding disorder that is caused by mutations in the factor VIII (FVIII) gene.
      About 25% of patients who receive replacement therapy with intravenous FVIII
      products develop neutralising antibodies (FVIII inhibitors) that inhibit the
      function of substituted FVIII. Long-term application of high or low doses of
      FVIII has evolved as an effective strategy for eradicating antibodies and
      inducing long-lasting immune tolerance. Despite clinical experience with the
      therapy, little is known about the immunological mechanisms that cause the down
      modulation of FVIII-specific immune responses or the induction of long-lasting
      immune tolerance against FVIII. This review summarises current knowledge of the
      immunological mechanisms that might be involved in the induction of immune
      tolerance against FVIII in patients with haemophilia A who have FVIII inhibitors.
      In addition to data from patients with haemophilia A, data from patients who have
      had organ transplants or have immune-related disorders, such as autoimmune
      diseases, are considered as well as data from animal models.

PMID- 17222197
TI  - 6q deletion in Waldenstrom macroglobulinemia is associated with features of
      adverse prognosis.
AB  - Fluorescence in situ hybridisation (FISH) is an effective technique for the
      cytogenetic analysis of Waldenstrom macroglobulinemia (WM), but the potential
      impact of molecular cytogenetics on disease evolution and as a prognostic marker
      is still unknown. Deletion of the long arm of chromosome 6 (6q-) is the most
      frequent cytogenetic abnormality in WM. This study analysed the prevalence of
      this aberration in 102 WM patients, and correlated it with disease
      characteristics. The incidence of 6q21 deletion was 7% by conventional
      cytogenetics and 34% when analysed by FISH (54% when cytoplasmic immunoglobulin M
      FISH was used). Patients with deletion of 6q displayed features of adverse
      prognosis, such as higher levels of beta2-microglobulin and monoclonal
      paraprotein and a greater tendency to display anaemia and hypoalbuminemia.
      Interestingly, there was a correlation between the presence of 6q deletion and
      the International Staging System prognostic index (incidence of 6q- among
      patients stratified in stages 1, 2 and 3 was 24%, 42% and 67% respectively).
      Those patients diagnosed with smouldering WM who displayed the abnormality showed
      a trend to an earlier requirement of treatment. Finally, the survival analysis
      did not show differences between the two groups of patients, probably due to the
      short follow up of our series.

PMID- 17222198
TI  - Case-control study of multidrug resistance phenotype and response to induction
      treatment including or not fludarabine in newly diagnosed acute myeloid leukaemia
      patients.
AB  - One hundred and six patients aged </=60 years with newly diagnosed acute myeloid
      leukaemia (AML) treated with fludarabine-based regimens (cases) were matched with
      106 AML patients treated with conventional non-fludarabine-based regimens
      (controls). The cases and controls were matched by expression of the multidrug
      resistance P-glycoprotein (MDR-Pgp), measured by flow cytometry as mean
      fluorescence index (MFI), cytogenetics, and age. The complete remission (CR) rate
      of the cases was 61% among the MDR-Pgp-positive (pos(ve)) patients (MFI >/= 6)
      vs. 75% among the MDR-Pgp-negative (neg(ve)) ones (MFI < 6) (P = 0.16).
      Conversely, in the controls, the CR rate was 44% among the MDR-Pgp-pos(ve)
      patients vs. 67% among the MDR-Pgp-neg(ve) ones (P = 0.02). The 4-year disease
      free survival (DFS) and overall survival (OS) of MDR-Pgp-pos(ve) cases were
      significantly longer than those of MDR-Pgp-pos(ve) controls (DFS, 28.1% vs. 6.5%,
      P = 0.004; OS, 33.5% vs. 9.6%, P = 0.01). This difference was not found among the
      MDR-Pgp-neg(ve) patients. By univariate (P = 0.007) and multivariate (P = 0.007)
      analysis, the MDR-Pgp-pos(ve) phenotype was negatively correlated with CR and it
      emerged as the most important independent negative prognostic factor, after
      cytogenetics. Our study confirms the prognostic impact of the MDR phenotype in
      AML and strongly suggests fludarabine-based induction treatments as a promising
      strategy for MDR-Pgp-pos(ve) AML patients. In this setting of patients, large
      prospective randomised studies should be planned.

PMID- 17222199
TI  - Bortezomib disrupts tumour-dendritic cell interactions in myeloma and lymphoma:
      therapeutic implications.
AB  - Recent studies have shown that the interactions between tumour and dendritic
      cells (DCs) promote clonogenic growth of lymphoproliferative tumours,
      particularly myeloma. The present study showed that the proteasome inhibitor,
      bortezomib, disrupts this interaction. Targeting the drug to DCs was required for
      optimal suppression of tumour growth, including primary myeloma tumour
      progenitors in clonogenic assays. Bortezomib lead to dose-dependent induction of
      apoptosis in both myeloid and plasmacytoid DCs, and the sensitivity of DCs to
      bortezomib was comparable with that of tumour cells. These data suggest that
      disruption of tumour-DC interactions may contribute to the clinical effects of
      bortezomib.

PMID- 17222200
TI  - Reduced-intensity conditioning followed by T-cell depleted allogeneic stem cell
      transplantation for patients with chronic myeloid leukaemia and minimal residual
      disease at the time of transplant: high risk of molecular relapse.
AB  - A pilot trial was initiated for chronic myeloid leukaemia patients, which
      employed imatinib for remission induction, followed by reduced-intensity
      conditioning and an in vivo T-cell depleted graft. Out of nine patients, six
      experienced a molecular relapse and one patient had a haematological relapse at a
      median interval of 5 months after transplantation. Five relapsing patients
      achieved a 2nd molecular remission after treatment with either donor lymphocyte
      infusions (n = 4) or imatinib (n = 1). Two of nine patients died due to
      infectious complications. The probability of survival 2 years after transplant
      was 74% (95% CI 42-100%).

PMID- 17222201
TI  - In vitro kinetics of factor VIII activity in patients with mild haemophilia A and
      a discrepancy between one-stage and two-stage factor VIII assay results.
AB  - In some mild haemophilia A patients (discrepant haemophilia), factor VIII
      coagulant activity (FVIII:C) levels, by one-stage assay are more than double than
      those by two-stage assay. This may be due to the longer incubation times (10-12
      min) in the two-stage assay. This study aimed to determine the time course of the
      activation phase of the two-stage assay, using both classical coagulation and
      chromogenic detection methods. In both systems, for equivalent patients
      (equivalent FVIII:C levels by one-stage and two-stage assays, n = 6, all
      different mutations), similar FVIII:C results were obtained with short- or long
      incubation times. In contrast, plasma from discrepant patients (n = 8, five
      different mutations) showed higher FVIII:C at shorter incubation times than after
      longer incubation times. In the chromogenic assay, FVIII:C levels were higher
      after incubation for 2 min (23-56%, mean 41%) than after 10 min (19-41%, mean
      29%). In the classical coagulation assay, FVIII:C levels were higher at shorter
      incubation times (21-64%, mean 37%) than with the longer incubation times usually
      used (13-29%, mean 23%). These time-course experiments have verified that the
      longer incubation time used in the two-stage assay is at least partly responsible
      for the lower FVIII:C measured by that assay in discrepant haemophilia.

PMID- 17222202
TI  - A novel beta-delta globin gene fusion, anti-Lepore Hong Kong, leads to
      overexpression of delta globin chain and a mild thalassaemia intermedia phenotype
      when co-inherited with beta(0)-thalassaemia.
AB  - Anti-Lepore haemoglobins (Hb) are rare betadelta fusion variants that arise from
      non-homologous crossover during meiosis, resulting in a delta-betadelta-beta
      configuration. A novel anti-Lepore mutation (anti-Lepore Hong Kong) was found in
      two Chinese families with raised Hb A(2). Direct sequencing revealed a crossover
      within a 54-bp region spanning the junction of cap site (CAP) and exon 1, which
      predicted the production of normal delta-globin. Determination of alpha/beta-mRNA
      ratios by quantitative real-time polymerase chain reaction demonstrated
      downregulation of the beta gene in cis due to the interposed betadelta fusion
      gene. Although heterozygotes have normal red cell indices and are clinically
      silent, compound heterozygotes with beta(0) mutation in trans produce a mild
      thalassaemia intermedia phenotype with a markedly raised Hb A(2) level that may
      mimic clinically mild Hb E-beta(+)-thalassaemia. Awareness of the presence of
      anti-Lepore Hong Kong will help to resolve diagnostic problems in regions with
      significant prevalence of globin disorders.

PMID- 17222203
TI  - Cyclooxygenase-2 (COX-2) in multiple myeloma: prognostic factor or therapeutic
      target?

PMID- 17222205
TI  - Molecular characterisation of pyruvate kinase deficiency--concerns about the
      description of mutant PKLR alleles.

PMID- 17222208
TI  - Effect of Matrigel on adenoid cystic carcinoma cell line differentiation.
AB  - Adenoid cystic carcinoma (ACC) is a frequent malignant salivary gland neoplasm
      presenting different growth patterns described as tubular, cribriform and solid,
      which represent distinct differentiation stages. Cell lines originated from ACCs
      grown inside three-dimensional environments have not been capable to reproduce
      all in vivo ACC growth patterns. As ACC cells in vivo present replicated basement
      membrane, to mimic this situation in vitro ACC cells (CAC2 cells) were grown on
      the top of a reconstituted basement membrane (Matrigel). Phenotype differences
      were assessed by light, fluorescence and transmission electron microscopy. The
      cultures grown on the top of Matrigel presented three-dimensional arrangement of
      cells intercepted by cellular cords. At these, cell nests pseudocyst formations
      were observed. This morphological structure entirely reproduced the cribriform
      growth pattern of ACC. We suggest that the cribriform differentiation of ACC in
      culture is dependent of proteins and growth factors associated in a bi
      dimensional structure.

PMID- 17222209
TI  - Recovery of rat submandibular salivary gland function following removal of
      obstruction: a sialometrical and sialochemical study.
AB  - Functional recovery of the rat submandibular gland following ligation of the main
      excretory duct was examined. Rat submandibular glands were ligated for 1, 4 and 8
      weeks using a micro-clip with a plastic tube. Micro-clips were removed and glands
      were allowed to recover for periods of 8, 16 and 24 weeks. Submandibular glands
      were stimulated with autonomimetic drugs (methacholine and isoprenaline) and
      salivas were collected from atrophic or de-ligated and contralateral control
      glands. Glands recovered almost full size (92% of control gland) following 24
      weeks of de-ligation. Saliva volume secreted by ligated/de-ligated (RSM) and
      control (LSM) glands were similar with different doses of agonists. Protein
      output expressed per gram of tissue wet weight was similar from both ligated/de
      ligated and control glands with all doses of agonist. Sodium and chloride levels
      were higher from de-ligated glands than contralateral control glands. Protein
      electrophoresis showed similar profiles of salivary proteins in all samples with
      some minor differences. Acinar cells in de-ligated glands showed a normal
      morphology, as indicated by light microscopy, whilst granular ductal cells were
      fewer and contained fewer secretory granules. Sodium potassium ATPase staining of
      striated ducts in de-ligated glands was similar to that of control glands. It can
      be concluded that rat submandibular glands can regenerate following severe
      atrophy and secrete normal amounts of saliva containing broadly a full profile of
      secretory proteins. In contrast to acinar cells, ductal cells appear not to
      recover full function.

PMID- 17222210
TI  - Circumferential wall tension due to hypertension plays a pivotal role in aorta
      remodelling.
AB  - The present study was carried out to investigate the role of hypertension in the
      genesis and localization of intimal lesions and medial remodelling found in the
      prestenotic segment in relation to a severe stenosis of the abdominal aorta just
      below the diaphragm. Male young rats were divided randomly into operated group,
      animals submitted to surgical abdominal aorta stenosis, and sham-operated group,
      a control group of animals submitted to sham operation to simulate abdominal
      aorta stenosis. Aortas in the hypertensive prestenotic segment with increased
      circumferential wall tension associated with normal tensile stress, laminar
      flow/normal wall shear stress were characterized by enlarged heterogeneous
      endothelial cells elongated in the direction of the blood flow, diffusely
      distributed conspicuous neointimal plaques and medial thickening. The
      immunohistochemical analysis revealed an increased expression of eNOS, iNOS,
      nitrotyrosine and transforming growth factor-beta (TGF-beta) in endothelial cells
      and/or smooth muscle cells in this segment. Our findings suggest that increased
      circumferential wall tension due to hypertension plays a pivotal role in the
      remodelling of the prestenotic segment through biomechanical effects on oxidative
      stress and increased TGF-beta expression. Further studies are needed to clarify
      the intrinsic pathogenetic mechanism of focal distribution of the neointimal
      plaques in the hypertensive segment.

PMID- 17222211
TI  - Heart failure alters matrix metalloproteinase gene expression and activity in rat
      skeletal muscle.
AB  - Heart failure is associated with a skeletal muscle myopathy with cellular and
      extracellular alterations. The hypothesis of this investigation is that
      extracellular changes may be associated with enhanced mRNA expression and
      activity of matrix metalloproteinases (MMP). We examined MMP mRNA expression and
      MMP activity in Soleus (SOL), extensor digitorum longus (EDL), and diaphragm
      (DIA) muscles of young Wistar rat with monocrotaline-induced heart failure. Rats
      injected with saline served as age-matched controls. MMP2 and MMP9 mRNA contents
      were determined by RT-PCR and MMP activity by electrophoresis in gelatin
      containing polyacrylamide gels in the presence of SDS under non-reducing
      conditions. Heart failure increased MMP9 mRNA expression and activity in SOL, EDL
      and DIA and MMP2 mRNA expression in DIA. These results suggest that MMP changes
      may contribute to the skeletal muscle myopathy during heart failure.

PMID- 17222212
TI  - Immunohistochemical detection of myogenin and p21 in methylcholanthrene-induced
      mouse rhabdomyosarcomas.
AB  - 3-Methylcholanthrene (MC)-induced 10 embryonal (ERSs) and 24 pleomorphic
      rhabdomyosarcomas (PRSs) of the dermis in mouse were examined
      immunohistochemically for myogenin, p21 and proliferating cell nuclear antigen
      (PCNA) nuclear reactivity and myosin reactivity. ERSs had higher expression of
      myogenin and p21 compared with that of myosin. PRSs were divided into two groups
      having high (moderate or marked reactivity; HLM) and low (mild reactivity; LLM)
      levels of myosin expression. Expression of p21 was higher in HLM-PRSs than in LLM
      PRSs. Statistically significant association was observed between myosin and p21
      expression in PRSs, but not between myosin and myogenin expression. Myogenin and
      p21 reactivity were observed in myoblast-like cells, but rarely in multinucleated
      cells. In ERSs, small undifferentiated myogenic precursor cells were also
      positive for p21. No difference of PCNA reactivity was observed between HLM-PRSs
      and LLM-PRSs, although its reactivity was higher in PRSs than in ERSs. The
      results suggest that myogenin is related to myoblast-like cell differentiation in
      PRSs and that p21 plays essential roles in myotube formation and myosin
      expression. In ERSs, p21 may be involved in inhibition of myogenic precursor cell
      proliferation and differentiation.

PMID- 17222213
TI  - The effects of glucocorticoid therapy on the inflammatory and dendritic cells in
      muscular dystrophies.
AB  - Various clinical trials have documented the therapeutic benefit of
      glucocorticoids (GCs) in enhancing muscle strength and slowing disease
      progression of Duchenne and Becker muscular dystrophies (DMD/BMD). We
      hypothesized that GCs may have relevance to the differential anti-inflammatory
      effect on mononuclear inflammatory cells (MICs) and Dendritic cells (DCs)
      infiltrating the dystrophic muscles. In this prospective study, two muscle
      biopsies were obtained (before and after 6-month prednisone therapy) from 30
      patients with dystrophies (DMD = 18; BMD = 6; and limb girdle muscular
      dystrophies (LGMD) = 6). MICs and DCs infiltrating the muscles were examined
      using mouse monoclonal antibodies and immunoperoxidase staining methods. Muscle
      strength was evaluated monthly by manual testing, motor ability and timed tests.
      Prednisone therapy was associated with: (i) functional improvement of overall
      motor disability, in upper limbs of DMD (P < 0.001) and BMD (P < 0.01) and lower
      limbs of DMD (P < 0.001) and BMD (P < 0.05); (ii) histological improvement such
      as fibre size variation (DMD, P < 0.01; BMD, P < 0.05), internalization of nuclei
      (DMD, P < 0.05), degeneration and necrosis (DMD and BMD, P < 0.01), regeneration
      (DMD, P < 0.001; BMD, P < 0.01) and endomysial connective tissue proliferation
      (DMD, P < 0.01; BMD, P < 0.05) and (iii) reduction of total MICs (P < 0.01) and
      DCs (P < 0.01). There was a positive correlation between the degree of
      improvement in overall motor disability and reduction of DCs numbers (In upper
      limbs; r = 0.638, P < 0.01 for DMD and r = 0.725, P < 0.01 for BMD, in Lower
      limbs; r = 0.547, P < 0.05 for DMD and r = 0.576, P < 0.05 for BMD). Such
      improvements and changes of MICs/DCs were absent in LGMD. In DMD/BMD, prednisone
      therapeutic effect was associated with reduced MICs and DCs numbers. Whether this
      therapeutic effect reflects targeting of the deleterious immune response produced
      by these cells mandates further investigations.

PMID- 17222214
TI  - Transdifferentiation of pulmonary arteriolar endothelial cells into smooth muscle
      like cells regulated by myocardin involved in hypoxia-induced pulmonary vascular
      remodelling.
AB  - Myocardin gene has been identified as a master regulator of smooth muscle cell
      differentiation. Smooth muscle cells play a critical role in the pathogenesis of
      hypoxia-induced pulmonary hypertension (PH) and pulmonary vascular remodelling
      (PVR). The purpose of this study was to investigate the change of myocardin gene
      expression in the pulmonary vessels of hypoxia-induced PH affected by Sildenafil
      treatment and the involvement of endothelial cells transdifferentiation into
      smooth muscle cells in the process of hypoxia-induced PH and PVR. Myocardin and
      relative markers were investigated in animal models and cultured endothelial
      cells. Mean pulmonary artery pressure (mPAP) was measured. Immunohistochemistry
      and immunofluorescence were used to show the expression of smooth muscle alpha
      actin (SMA), in situ hybridization (ISH) and reverse transcription polymerase
      chain reaction (RT-PCR) were performed respectively to detect the myocardin and
      SMA expression at mRNA levels. Small interfering RNA (siRNA) induced suppression
      of myocardin in cultured cells. We confirmed that hypoxia induced the PH and PVR
      in rats. Sildenafil could attenuate the hypoxia-induced PH. We found that
      myocardin mRNA expression is upregulated significantly in the hypoxic pulmonary
      vessels and cultured cells but downregulated in PH with Sildenafil treatment. The
      porcine pulmonary artery endothelial cells (PAECs) transdifferentiate into smooth
      muscle-like cells in hypoxic culture while the transdifferentiation did not occur
      when SiRNA of myocardin was applied. Our results suggest that myocardin gene, as
      a marker of smooth muscle cell differentiation, was expressed in the pulmonary
      vessels in hypoxia-induced PH rats, which could be downregulated by Sildenafil
      treatment, as well as in hypoxic cultured endothelial cells. Hypoxia induced the
      transdifferentiation of endothelial cells of vessels into smooth muscle-like
      cells which was regulated by myocardin.

PMID- 17222215
TI  - MCP-1/CCR2 signalling pathway regulates hyperoxia-induced acute lung injury via
      nitric oxide production.
AB  - To clarify the role of the monocyte chemoattractant protein-1 (MCP-1)/C-C
      chemokine receptor 2 (CCR2) signalling pathway in hyperoxia-induced acute lung
      injury, CCR2-deficient (CCR2-/-) and wild-type (CCR2+/+) mice were exposed to 85%
      O(2) for up to 6 days. At day 3, body weight significantly decreased and total
      protein concentration in bronchoalveolar lavage fluid (BALF) was higher in CCR2-/
      mice compared with CCR2+/+ mice. Cumulative survivals were significantly lower
      in CCR2-/- mice than in CCR2+/+ mice. However, the two groups showed no
      significant differences in both histological changes and number of macrophages in
      BALF. Real-time reverse transcriptase-polymerase chain reaction revealed
      increased mRNA levels of MCP-1, interleukin-1beta thioredoxin-1, and inducible
      nitric oxide synthase (iNOS) in lung tissues in CCR2-/- mice compared with
      CCR2+/+ mice. Increased iNOS mRNA levels in alveolar macrophages exposed to 85%
      O(2) for 48 h in vivo or in vitro were significantly higher in CCR2-/- mice than
      in CCR2+/+ mice. These results suggest that the MCP-1/CCR2 signalling pathway is
      protective against hyperoxia-induced tissue injury by suppressing induction of
      iNOS and consequent production of reactive oxygen species by activated alveolar
      macrophages.

PMID- 17222216
TI  - Expression of cyclooxygenase-2, alpha 1-acid-glycoprotein and inducible nitric
      oxide synthase in the developing lesions of murine leprosy.
AB  - Murine leprosy is a chronic disease of the mouse, the most popular animal model
      used in biomedical investigation, which is caused by Mycobacterium lepraemurium
      (MLM) whose characteristic lesion is the macrophage-made granuloma. From onset to
      the end of the disease, the granuloma undergoes changes that gradually transform
      the environment into a more appropriate milieu for the growth of M. lepraemurium.
      The mechanisms that participate in the formation and maturation of the murine
      leprosy granulomas are not completely understood; however, microbial and host
      factors are believed to participate in their formation. In this study, we
      analysed the role of various pro-inflammatory and anti-inflammatory proteins in
      granulomas of murine leprosy after 21 weeks of infection. We assessed the
      expression of cyclooxygenase-2 (COX-2), alpha acid-glycoprotein (AGP), and
      inducible nitric oxide synthase (iNOS) at sequential stages of infection. We also
      looked for the nitric-oxide nitrosylation product, nitrotyrosine (NT) in the
      granulomatous lesions of murine leprosy. We found that a pro-inflammatory
      environment predominates in the early granulomas while an anti-inflammatory
      environment predominates in late granulomas. No obvious signs of bacillary
      destruction were observed during the entire period of infection, but
      nitrosylation products and cell alterations were observed in granulomas in the
      advanced stages of disease. The change from a pro-inflammatory to an anti
      inflammatory environment, which is probably driven by the bacillus itself,
      results in a more conducive environment for both bacillus replication and the
      disease progression.

PMID- 17222217
TI  - Immunological hormone atrophy by gonadotropin-based drug.
AB  - Luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin A (LHRH
      PE40) and sequence-modified LHRH-PE40 (mLHRH-PE40) are two anti-tumour drugs
      developed by fusing either native or modified LHRH with the same PE40. This study
      was designed to evaluate their toxicity on the male genital tract. Male rats were
      treated intravenously or intraperitoneally with either LHRH-PE40 or mLHRH-PE40 on
      alternate days for 12 weeks. Serum and testes were examined to detect anti-LHRH,
      anti-LHRH-PE40 or anti-mLHRH-PE40 using an ELISA assay, testosterone level was
      measured by radioimmunoassay, and testicular morphology was evaluated. Rats
      receiving LHRH-PE40 intraperitoneal injections had higher anti-LHRH antibody
      titres, lower serum testosterone concentration and remarkable testicular atrophy,
      whereas those administrated with intravenous injections of either LHRH-PE40 or
      mLHRH-PE40 demonstrated no such changes. We concluded that the testicular atrophy
      can be attributed to higher titre of anti-LHRH antibodies, which was affected by
      both drug delivery and the LHRH motif of the chimeric protein.

PMID- 17222218
TI  - White blood cell sister chromatid exchange among a sample of Thai subjects
      exposed to toluene, an observation.
AB  - There is a particular concern with toluene because some research has indicated
      that toluene exposure could result in chronic toxicity including mutagenesis and
      carcinogenesis. This study aimed to determine the rate of sister chromatid
      exchanges (SCE), a marker for genotoxicity, and its correlation to the classical
      urine biomarker for toluene exposure, urine hippuric acid, among a sample of Thai
      exposed subjects. A total of 26 police (all males) were included in this study.
      The average (mean +/- SD) urine hippuric acid level in these police was 0.8 +/-
      0.4 mg/g creatinine. The average (mean +/- SD) SCE level in these police was 4.5
      +/- 1.0/cell. The average SCE among the police with high urine hippuric acid
      levels was non-significantly higher than the average SCE level of those without
      (P = 0.41). This implies that the cytogenetic response to toluene was not
      different between the subjects with and without high toluene exposure. High
      exposure to toluene seems not to be related to high SCE.

PMID- 17222219
TI  - Aneuploidy and proliferation in keratinocytic intraepidermal neoplasias.
AB  - Cutaneous squamous (pre)malignancies can be classified according to the
      keratinocytic intraepidermal neoplasia (KIN) classification. Aneuploidy can be
      seen as the result of chromosomal aberrations leading to altered DNA content and
      has been strongly associated with malignancy. Hyperproliferation is also strongly
      associated with tumorigenesis. The aim of the study was to analyse the presence
      and the amount of aneuploidy and proliferation in the progression from
      intraepithelial neoplasm to microinvasive carcinoma (miSCC). For this purpose,
      nuclei were isolated from 116 formalin-fixed KIN lesions from 68 patients in
      which DNA content was measured by flow cytometry. Proliferation was assessed by
      immunohistochemical staining for Ki67 as well as by flow cytometry. Aneuploidy
      was increasingly found in higher KIN lesions, but not in normal skin. However, in
      miSCC aneuploidy was relatively less frequently found. DNA indices (mean +/- SE)
      of KIN III-lesions (1.57 +/- 0.05) were significantly lower compared with KIN
      I/II lesions (1.71 +/- 0.05). Ki67 expression was strongly positively correlated
      with KIN grade, and proved to be a good adjunct in the classification of KINs.
      Thus, aneuploidy occurred more frequently in higher KIN lesions, indicating
      cumulative damage during KIN progression. The lower frequency of aneuploidy in
      miSCC compared with KIN III may point at alternative routes towards invasive
      carcinoma besides serial progression through all three KIN stages. Ki67
      expression appears a valuable marker in the classification of KINs.

PMID- 17222221
TI  - Sweat gland epithelial and myoepithelial cells are vitamin D targets.
AB  - Nuclear receptor binding of 1,25(OH)(2)-vitamin D(3) (vitamin D) in skin
      keratinocytes of epidermis, hair sheaths and sebaceous glands was discovered
      through receptor microscopic autoradiography. Extended experiments with (3)H
      1,25(OH)(2)-vitamin D(3) and its analog (3)H-oxacalcitriol (OCT) now demonstrate
      nuclear receptor binding in sweat gland epithelium of secretory coils and ducts
      as well as in myoepithelial cells, as studied in paws of nude mice after i.v.
      injection. The results suggest genomic regulation of cell proliferation and
      differentiation, as well as of secretory and excretory functions, indicating
      potential therapies for impaired secretion as in hypohidrosis of aged and
      diseased skin.

PMID- 17222220
TI  - Elevated serum BAFF levels in patients with localized scleroderma in contrast to
      other organ-specific autoimmune diseases.
AB  - Serum levels of B-cell activating factor belonging to the tumor necrosis factor
      family (BAFF), a potent B-cell survival factor, are elevated in patients with
      systemic autoimmune diseases, such as systemic lupus erythematosus (SLE),
      rheumatoid arthritis and systemic sclerosis (SSc). The objective of this study
      was to determine serum BAFF levels and relate the results to the clinical
      features in patients with organ-specific autoimmune diseases of the skin, such as
      localized scleroderma and autoimmune bullous diseases. Serum BAFF levels were
      examined by enzyme-linked immunosorbent assay in 44 patients with localized
      scleroderma, 20 with pemphigus vulgaris/pemphigus foliaceus, 20 with bullous
      pemphigoid and 30 healthy controls. Twenty patients with SSc and 20 with SLE were
      also examined as disease controls. Serum BAFF levels were elevated in localized
      scleroderma patients compared with healthy controls. Concerning localized
      scleroderma subgroups, patients with generalized morphea, the severest form of
      localized scleroderma, had higher serum BAFF levels than linear scleroderma or
      morphea patients. The BAFF levels of generalized morphea were comparable with
      those of SSc or SLE. Furthermore, serum BAFF levels correlated positively with
      antihistone antibody levels and the severity of skin lesion as well as the number
      of skin lesions. By contrast, serum BAFF levels were not significantly elevated
      in patients with pemphigus or pemphigoid. These results suggest that BAFF may be
      contributing to autoimmunity and disease development in localized scleroderma.

PMID- 17222223
TI  - Expression of the corticotropin-releasing hormone-proopiomelanocortin axis in the
      various clinical types of psoriasis.
AB  - Psychological stress is known to aggravate inflammatory skin diseases such as
      atopic dermatitis, psoriasis and contact sensitivity by altering the cellular
      constituents of the immune system. The skin appendages function dually as
      prominent targets and sources of the peripheral corticotropin-releasing hormone
      proopiomelanocortin (CRH-POMC) axis. In this study, we examined the expression
      level of CRH-POMC axis constituents in psoriasis, a well-known stress-related
      inflammatory skin disease. The 15 psoriasis patients and six normal controls were
      retrospectively selected after extensive review of their clinical records and
      skin biopsy specimens. We immunohistochemically analysed the expressivity of CRH,
      adrenocorticotrophic hormone (ACTH) and alpha-melanocyte-stimulating hormone
      (alpha-MSH) in various types of psoriatic lesions and control skin. A significant
      increase of CRH expression was observed in psoriatic lesions, which involved the
      entire epidermis (upper layer in particular), hair follicles and sweat glands
      compared with controls. Expression of ACTH and alpha-MSH was clearly stimulated
      in a subset of psoriasis patients compared with controls, but on the whole,
      lacked statistical significance. The immunoreactivity of CRH, ACTH and alpha-MSH
      in psoriasis was not dependent on its clinical subtype, duration or number of
      previous treatments. Compared with the definite increase of CRH expression in
      psoriasis, the expression of the POMC peptides was heterogenous with no overall
      significance. From the findings, we suggest that CRH, a key stress hormone, may
      play an important role in the pathomechanism of psoriasis.

PMID- 17222222
TI  - Spectral karyotyping demonstrates genetically unstable skin-homing T lymphocytes
      in cutaneous T-cell lymphoma.
AB  - We initially established cell lines from skin biopsies from four patients (MF8,
      MF18, MF19 and MF31) in early stages of cutaneous T-cell lymphoma (CTCL) in 1999.
      After 3 weeks of culture, skin-homing T lymphocytes were stimulated with
      phytohaemagglutinin. Metaphase spreads were analysed using spectral karyotyping
      (SKY), a molecular cytogenetic technique. MF18 and MF19 had predominantly normal
      karyotypes. MF8 had recurrent numerical aberrations resulting in two T lymphocyte
      clones: one with trisomy 21 (12/20 cells) and the other with monosomy chromosome
      22 (3/20 cells). MF8 also exhibited a clonal deletion, del(5)(p15.1), as well as
      multiple non-clonal structural aberrations. MF31 had a clonal deletion,
      del(17)(p12) and other non-clonal deletions involving chromosomes 2, 5, 10, 11.
      MF18 had a single abnormal cell that contained two reciprocal translocations
      t(1;2)(q32;p21) and t(4;10)(p15.2;q24). In 2001, three of the original patients
      had new skin biopsies taken and cell lines were established. SKY analysis
      revealed the continued presence of a T-cell clone in MF8 with trisomy 21 (4/20
      cells). Additionally, a new clone was seen with a del(18)(p11.2) (17/20 cells).
      MF31 had only one aberrant cell with a del(17)(p12). MF18 had a clonal deletion,
      [del(1)(p36.1) in 3/20 cells] and non-clonal aberrations involving chromosomes 3,
      4, 5, 6, 12, 13, 17 and 18. Thus, three of four patients continued to show
      numerous numerical and structural aberrations, both clonal and non-clonal, with
      only MF8 having a recurring T lymphocyte clone (+21). Our findings demonstrate
      high genetic instability among skin-homing T lymphocytes even in early stages of
      CTCL. We did not see genetic instability or evidence of clones in cell lines from
      a patient with atopic dermatitis and one with psoriasis.

PMID- 17222224
TI  - Influence of N-glycan processing disruption on tyrosinase and melanin synthesis
      in HM3KO melanoma cells.
AB  - Tyrosinase, a type I membrane glycoprotein, is synthesized and glycosylated in
      the endoplasmic reticulum (ER) and Golgi. The enzyme is subsequently transported
      to melanosomes where it participates in melanogenesis. Previous studies showed
      that the disruption of early ER N-glycan processing by deoxynojirimycin (DNJ), an
      inhibitor of alpha-glucosidase, suppresses tyrosinase enzymatic activity and
      melanogenesis. However, the disruption of late glycan processing, mainly
      performed by ER and Golgi alpha-1,2-mannosidases, on tyrosinase enzymatic
      activity and melanogenesis remains to be investigated. Following treatment of
      HM3KO human melanoma cells with deoxymannojirimycin (DMJ), an inhibitor of alpha
      1,2-mannosidase, transport of tyrosinase to the melanosome, enzymatic activity,
      and melanogenesis were reduced in a dose-dependent manner. However, DMJ did not
      directly inhibit tyrosinase enzymatic activity and expression. Interestingly, an
      extract of Streptomyces subrutilus culture medium (ESSCM) containing DMJ and DNJ
      as the main components inhibited glycosylation and transport of tyrosinase to the
      melanosome as well as melanin synthesis, but with no negative effects on cell
      viability. These inhibitory effects of ESSCM were stronger than those of DMJ or
      DNJ alone. Tyrosinase glycosylation and melanogenesis in HM3KO melanoma cells
      were more effectively inhibited by DMJ and DNJ combined than DMJ or DNJ alone.
      Accordingly, we propose that ESSCM is a potential candidate for treating
      undesirable hyperpigmentation conditions, such as melasma, postinflammatory
      melanoderma, and solar lentigo.

PMID- 17222225
TI  - PPAR-gamma agonist, ciglitazone, increases pigmentation and migration of human
      melanocytes.
AB  - Peroxisome proliferator-activated receptors (PPARs) play an important role in
      cellular responses. It was reported that three subtypes of PPAR are expressed in
      human melanocytes. In this study, we investigated the effects of the PPAR-gamma
      agonist, ciglitazone, on pigmentation and migration of human melanocytes.
      Ciglitazone stimulated the melanin content of cells and cultured skin. This
      increase in pigmentation was due to the stimulation of tyrosinase activity and
      expression of tyrosinase and microphthalmia-associated transcription factor
      protein of the melanocytes. Migration was increased after ciglitazone treatment,
      which was observed by the Boyden chamber checkerboard analysis and a scratch
      motility assay. These results suggest the regulatory role of PPAR-gamma in
      pigmentation and migration of human melanocytes.

PMID- 17222227
TI  - Detection of down-regulated acetaldehyde dehydrogenase 1 in atopic dermatitis
      patients by two-dimensional electrophoresis.
AB  - We conducted the proteomic studies to detect the dysregulated proteins in the
      atopic dermatitis (AD) proteome obtained from the patient-derived primary
      cultured fibroblasts. Acetaldehyde dehydrogenase 1 (ALDH1) was detected as being
      significantly down-regulated at the pH ranges of 6-9 and 4-7. The transcriptional
      levels of ALDH1, as detected by RT-PCR and real-time PCR, further confirmed the
      down-regulated phenomena for all the AD-fibroblasts (n = 20). The expression
      levels of ALDH1 in the whole skin tissue samples were further supported by the
      results of the primary cultured samples. These findings clearly demonstrate that
      ALDH1 can be a dermal biomarker for AD disease.

PMID- 17222226
TI  - Staphylococcus aureus-derived enterotoxins enhance house dust mite-induced patch
      test reactions in atopic dermatitis.
AB  - BACKGROUND: Up to 65% of Staphylococcus aureus strains isolated from the skin of
      patients with atopic dermatitis (AD) produce exotoxins with superantigenic
      properties that may also act as allergens leading to an induction of exotoxin
      specific IgE antibodies. Staphylococcal enterotoxin B (SEB) applied
      epicutaneously in a concentration of 10 micro g/cm(2), i.e. 200 micro g/ml, under
      occlusion induces cutaneous inflammation in patients with AD and healthy
      individuals. METHODS: We performed patch tests in 32 adult patients with AD using
      different concentrations (i.e. 2-200 micro g/ml) of SEA, SEB and house dust mite
      (HDM) extract (500 micro g/ml). Furthermore, the respective enterotoxins and HDM
      extract were applied simultaneously to the same patch test site. Specific IgE
      levels to SEA, SEB and HDM were measured with the CAP FEIA. RESULTS: The rates of
      patch test reactions to SEA and SEB increased with rising enterotoxin
      concentrations. There were no differences in the rates of patch test reactions to
      SEA and SEB between patients sensitized to the corresponding enterotoxin and non
      IgE-sensitized patients. The number of patch test reactions to the mixture of
      enterotoxin and HDM extract was higher than the number of patch test reactions to
      either the enterotoxins or HDM extract. We identified 11 patients with AD who
      reacted neither to the enterotoxins nor to HDM extract, but who showed patch test
      reactions to the mixture. These reactions were not predicted by the presence of
      enterotoxin- or HDM-specific IgE. CONCLUSIONS: Colonization with exotoxin
      producing S. aureus may influence the outcome of patch tests in patients with AD.

PMID- 17222228
TI  - Development and characterization of a canine skin equivalent.
AB  - The development of a complex cellular model, which incorporates the basic cell
      components of the dog skin, would be a useful tool to investigate the biology and
      pathology of canine skin and also to replace animal testing partially. The aim of
      the present study was to develop and characterize a canine skin equivalent.
      Epidermal keratinocytes and dermal fibroblasts were freshly isolated from skin
      biopsies from healthy dogs. Fibroblasts were embedded into a bio-matrix from
      collagen type I matrix protein; this built the scaffold where the keratinocytes
      were seeded, at air exposed conditions. At 3, 7, 15 and 21 days of culture in
      special growth media, skin equivalents were analysed by histological,
      immunohistochemical and electron microscopical techniques. At 15 days,
      keratinocytes underwent differentiation to a multilayer epidermis with stratum
      basal, stratum spinosum, stratum granulosum and stratum corneum. Expression of
      epidermal cytokeratins in keratinocytes was detected by immunhistochemistry, and
      followed the same pattern than in the normal canine epidermis. Fibroblasts from
      the skin equivalent expressed vimentin as dermal fibroblasts do. A basement
      membrane (BM) was observed underneath the epidermis; ultrastructurally, it was
      similar to the normal canine BM and collagen IV and laminin 5 were detected
      immunohistochemically as major components of this structure. Skin equivalents
      developed from canine cutaneous cells presented a similar morphological structure
      than healthy canine skin. Moreover, the immunohistochemical analysis revealed the
      expression of the major markers of the epidermis (keratins), dermis (vimentin)
      and BM (collagen type IV, laminin 5).

PMID- 17222229
TI  - The combination of ubiquitous transcription factors AP-1 and Sp1 directs
      keratinocyte-specific and differentiation-specific gene expression in vitro.
AB  - Previous studies of epidermal-specific gene promoters suggested that a limited
      set of transcription factors regulate keratinocyte-specific and differentiation
      specific gene expression in the epidermis. In the present study, we investigated
      the functional importance of AP-1- and Sp1-binding elements in the determination
      of cell type-specific and differentiation-specific gene expression by transient
      transfection into undifferentiated and differentiated keratinocytes as well as
      into various non-epidermal cell lines. Synthesized short AP-1- and/or Sp1-binding
      elements were inserted into a minimal reporter vector, and the artificial
      promoter containing both AP-1 and Sp1 elements showed high levels of
      transcriptional activity only when transfected into differentiated keratinocytes.
      Promoters containing either the AP-1 or the Sp1 motif alone showed little
      activity in any of the cells examined. We also found that close proximity of the
      Sp1 and AP-1 sites is essential for transcriptional activity, suggesting that the
      physical interaction between Sp1 and AP-1 factors is important for functional
      activity. These results clearly demonstrate that the combination of ubiquitously
      expressed transcription factors AP-1 and Sp1 confers keratinocyte specificity and
      differentiation specificity on the gene expression. Our findings also provide a
      simple model of the mechanisms underlying regulation of cell type-specific and
      cell differentiation-specific gene expression by ubiquitously expressed
      transcription factors.

PMID- 17222230
TI  - Quantitative analysis of the synthesis and secretion of type VII collagen in
      cultured human dermal fibroblasts with a sensitive sandwich enzyme-linked
      immunoassay.
AB  - Type VII collagen is the major component of anchoring fibrils in the epidermal
      basement membrane. Its expression has been analyzed by immunostaining or Northern
      blotting, but rarely at the protein level. In this study, we have quantitatively
      examined the effects of ascorbic acid and various cytokines/growth factors on the
      protein synthesis and secretion of type VII collagen by human dermal fibroblasts
      in culture, using a developed, highly sensitive sandwich enzyme-linked
      immunoassay with two kinds of specific monoclonal antibodies against the non
      collagenous domain-1. Ascorbic acid and its derivative induced a twofold increase
      in type VII collagen synthesis, and markedly increased the secretion of type VII
      collagen into the medium when compared with the control culture. This effect was
      not influenced by the presence of transforming growth factor-beta1 (TGF-beta1).
      The synthesis of type VII collagen was elevated by TGF-beta1, platelet-derived
      growth factor, tumor necrosis factor-alpha, and interleukin-1beta, but not by TGF
      alpha. Thus, our data indicate that the synthesis and secretion of type VII
      collagen in human dermal fibroblasts are regulated by ascorbate and the
      enhancement of type VII collagen gene expression by cytokines/growth factors is
      accompanied with elevated production of type VII collagen at the protein level.

PMID- 17222233
TI  - Equine sweating and anhidrosis Part 2: anhidrosis.
AB  - The condition of anhidrosis is described in this review, and the latest theories
      on the causal factors are explored. The evidence supports the hypothesis that
      anhidrosis is an inappropriate response to prolonged climatic stress (generally
      combined heat and high humidity), which can be evoked in a small (approximately
      10 +/- 5%) proportion of the equine population. It is caused by gradual failure
      of the glandular secretory cell processes, initiated by desensitization and
      subsequent down-regulation of the cell receptors as a result of continued
      adrenaline-driven hyperactivity. It progresses through secretory failure and
      culminates in gradual, probably irreversible, glandular dedifferentiation and
      ultimate degeneration. There is a need for considerably more research on the
      secretory and transcriptional processes to document the changes arising within
      the glandular secretory mechanism as a prelude to development of a corrective
      treatment.

PMID- 17222234
TI  - Upregulation of c-Myc may contribute to the pathogenesis of canine pemphigus
      vulgaris.
AB  - The pathomechanism in human pemphigus vulgaris (PV) has recently been described
      to rely on generalized c-Myc upregulation in skin and oral mucosa followed by
      hyperproliferation. Here we assessed whether dogs suffering from PV present the
      same pathological changes as described for human patients with PV. Using
      immunofluorescence analysis on patients' biopsy samples, we observed marked
      nuclear c-Myc accumulation in all layers of the epidermis and oral mucosa in all
      (3/3) dogs analysed. In addition, c-Myc upregulation was accompanied by an
      increased number of proliferating Ki67-positive cells. These molecular changes
      were further paralleled by deregulated expression of wound healing and terminal
      differentiation markers as observed in human PV. Together these findings suggest
      a common pathomechanism for both species which is of particular relevance in the
      light of the recently discussed novel therapeutic strategies aiming at targeting
      PV antibody-induced signalling cascades.

PMID- 17222235
TI  - Use of selamectin for the treatment of psoroptic and sarcoptic mite infestation
      in rabbits.
AB  - Selamectin, a novel avermectin compound, was evaluated for its efficacy against
      naturally occurring infestations of Psoroptes cuniculi and Sarcoptes scabiei. A
      total of 42 New Zealand rabbits with psoroptic mange and 37 Angora rabbits with
      sarcoptic mange were used in the present study. On day 0, infested rabbits were
      treated topically with either selamectin at minimum dose of 6 mg kg(-1) (6-18 mg
      kg(-1) for New Zealand rabbits, n = 31 and 10-12 mg kg(-1) for Angora rabbits, n
      = 23) or vehicle only (control groups, n = 11 for New Zealand rabbits, n = 14 for
      Angora rabbits). The efficacy of selamectin was assessed both clinically and
      parasitologically by the presence or absence of viable mites. Rabbits were
      scraped for sarcoptic mites on days 7, 14, 28, 42 and 56 and had otoscopeic
      and/or microscopic examination for the detection of Psoroptes mites on days 7,
      14, 42 and 56. Fisher's exact test was used to assess differences between the
      vehicle and selamectin treatment in the number of rabbits without mites (cure
      rates) on each assessment date. It was found that significantly fewer selamectin
      treated rabbits had mites detected on skin scrapings (for S. scabiei) or
      otoscopeic and/or microscopic examination (for P. cuniculi) (P < 0.01) than the
      vehicle group. Results of the present study suggest that selamectin is effective
      against naturally infestations of P. cuniculi and S. scabiei in rabbits.

PMID- 17222236
TI  - Familial ichthyosiform keratoderma in newly out-of-pouch Bennett's wallabies
      (Macropus rufogriseus) and report of two cases.
AB  - Primary inherited disorders of cornification in veterinary medicine are uncommon
      and rarely reported. Herein described is a unique syndrome associated with
      keratoderma that occurred in two Bennett's wallaby siblings (Macropus
      rufogriseus), and was characterized by profound thickening of the pad skin of all
      feet, generalized scaling of haired skin, and death within 7 weeks of out-of
      pouch experience. The male also had depressed serum zinc levels. In addition, the
      male had, on electron microscopic exam of his skin, the presence of abnormal
      lipid deposits within the stratum corneum and stratum granulosum. The combination
      of clinical features and electron microscopic findings strongly suggests a
      syndrome analogous to harlequin ichthyosis or lamellar ichthyosis in humans.

PMID- 17222237
TI  - Staphylococcal and micrococcal adherence to canine and feline corneocytes:
      quantification using a simple adhesion assay.
AB  - In this paper a simple adhesion assay suitable for the assessment of bacterial
      adhesion to both canine and feline corneocytes is described. Using this assay
      Staphylococcus intermedius, Staphylococcus aureus and Staphylococcus chromogenes
      were shown to adhere well to both canine and feline corneocytes. The numbers of
      adherent bacteria were, however, generally lower for feline corneocytes. Both
      Staphylococcus hominis and a Micrococcus species adhered poorly to canine and
      feline corneocytes. This is the first report documenting bacterial adhesion to
      feline corneocytes.

PMID- 17222238
TI  - Clinical and pathological findings in a HERDA-affected foal for 1.5 years of
      life.
AB  - A Quarter horse filly bred from two horses affected with HERDA (hereditary equine
      regional dermal asthenia) was observed clinically and its skin histologically for
      the 1.5 years of its life. Severe signs of the disease did not manifest until 1.5
      years of age, and were not temporally related to saddling. Histological
      comparison to an age-, breed- and sex-matched control did not show any consistent
      diagnostic features. Monitoring of the proband substantiated previous reports of
      (i) the autosomal recessive nature of the disease, (ii) mares affected with HERDA
      being able to foal without damage to the skin or reproductive tract, (iii) HERDA
      foals appearing phenotypically normal throughout the first year of life, and (iv)
      demonstrated that histological interpretation of skin specimens from grossly
      normal skin may be insufficient to differentiate HERDA-affected horses from
      controls.

PMID- 17222239
TI  - Suspected toxic shock-like syndrome in a dog with closed-cervix pyometra.
AB  - Several cases of toxic shock-like syndrome (TSLS) have been reported in dogs but
      no inciting cause has been identified. TSLS associated with a closed-cervix
      pyometra was suspected in the reported bitch. The dog was evaluated for the
      complaint of generalized dermatopathy (erythema and oedema) and systemic signs
      with multiorganic involvement (depression, fever, immature neutrophilia,
      hypoalbuminaemia, renal disease, vomiting and diarrhoea). Histological features
      consistent with TSLS included superficial dermatitis with epidermal neutrophilic
      exocytosis and necrotic keratinocytes. The tentative diagnosis of TSLS was based
      on case history, clinical presentation, laboratory and histopathological
      findings, and the resolution of all clinical signs following surgical removal of
      the localized bacterial infection.

PMID- 17222240
TI  - Cutaneous and ocular adverse reactions in a dog following meloxicam
      administration.
AB  - The present report addresses the development of cutaneous and ocular reactions
      possibly related to meloxicam administration in a dog. Based on clinical signs
      and absence of laboratory data compatible with the other differential diagnoses
      considered, the possibility of an adverse drug reaction (ADR) due to meloxicam
      was considered. Skin biopsy revealed haemorrhage of the superficial and deep
      dermis, associated with hyperplasia of endothelial cells and epidermal sloughing.
      Vasculitis in the deep dermis was also noted. Such lesions were considered
      compatible with an ADR. Although the owner was not aware of any previous allergic
      reaction to drugs, the animal had a clinical history of atopic dermatitis.
      Meloxicam is a nonsteroid anti-inflammatory drug (NSAID) in the oxicam family,
      indicated for the control of inflammation and pain in acute and chronic
      musculoskeletal disorders in dogs. Although meloxicam is usually well tolerated,
      the present clinical case represents an alert to practitioners about the
      potential role of NSAIDS in ADRs in dogs with a history of allergic cutaneous
      diseases.

PMID- 17222241
TI  - Feline herpes dermatitis treated with interferon omega.
AB  - This case report describes the diagnosis, demonstration and treatment of feline
      herpes virus-induced facial dermatitis in a cat. The cat was successfully treated
      with interferon omega (IFN-omega).

PMID- 17222242
TI  - Use of isolated infected spores to determine the sporocidal efficacy of two
      commercial antifungal rinses against Microsporum canis.
AB  - In this study, isolated infective Microsporum canis spores were used in an in
      vitro test model to compare the sporocidal activity of two commercial topical
      antifungal rinses. The two commercial test solutions used in the study were a
      lime sulphur solution 97.8% (LymDyp) and miconazole base 5.2%/chlorhexidine
      gluconate 5.9% mixture (Malaseb Concentrate Rinse). Water and household bleach
      were used as controls. Isolated infective spores were harvested from infected
      hairs and 500 microL of the spore suspension was incubated with an equal volume
      of dilutions of lime sulphur or the miconazole/chlorhexidine gluconate
      combination for 5 min and 4 h followed by fungal culture. There were too many to
      count colonies on the water control plates. Lime sulphur was 100% sporocidal at
      all test dilutions at both times. Miconazole/chlorhexidine gluconate was 100%
      sporocidal at all but the 1 : 128 dilution after 5 min of incubation and 100%
      sporocidal when incubated with spores for 4 h. It is not known if the two
      products have similar antifungal activity against infective spores on or within
      hairs; however, based on the findings of this study there is good evidence to
      recommend either rinse as an adjuvant topical therapy in a dermatophyte treatment
      and control program.

PMID- 17222243
TI  - Efficacy of topical eprinomectin in the treatment of Chorioptes sp. infestation
      in alpacas and llamas.
AB  - Chorioptes sp. mite infestation is increasingly recognized as a cause of skin
      disease in New World camelids and there is a need for an effective treatment
      protocol to eliminate herd infestation. In this field trial, eprinomectin applied
      topically at the rate of 0.5 mg kg(-1) weekly for 10 weeks was found to be
      ineffective in a herd of 12 llamas and 16 alpacas.

PMID- 17222244
TI  - Oestrogen receptor antagonist and hair regrowth in dogs with hair cycle arrest
      (alopecia X).
AB  - An oestrogen receptor pathway that regulates the telogen-anagen hair follicle
      transition in mice has been described. The purpose of this study was to
      investigate whether fulvestrant, a pure oestrogen receptor antagonist, would
      cause hair regrowth in Pomeranian dogs with hair cycle arrest (alopecia X).
      Eleven Pomeranian dogs with hair cycle arrest were randomly assigned to receive
      two intramuscular injections of either 10 mg kg(-1) fulvestrant (n = 6) or an
      equal volume of saline (n = 5) 1 month apart. Complete blood count, chemistry
      panel, and urinalysis were monitored prior to the first injection and monthly for
      2 months. Dogs were evaluated each month for degree of hair growth, percentage of
      body affected, and quality of new hair growth. Three control dogs received
      fulvestrant after the completion of the study. In addition, one control dog and
      one treatment dog received two subcutaneous injections of 20 mg kg(-1)
      fulvestrant 1 month apart. No dogs that received 10 mg kg(-1) fulvestrant had any
      evidence of hair regrowth. The control dog that received 20 mg kg(-1) fulvestrant
      had substantial hair regrowth 1 month after the first injection. No adverse
      effects from the treatment were noted. Fulvestrant does not appear to be a
      feasible treatment for dogs with hair cycle arrest (alopecia X) when administered
      intramuscularly at 10 mg kg(-1). A higher dose of fulvestrant requires more
      investigation but may be cost-prohibitive.

PMID- 17222245
TI  - Straelensiosis in a dog in Spain.

PMID- 17222246
TI  - Interstitial cells of Cajal in health and disease. Part I: normal ICC structure
      and function with associated motility disorders.
AB  - Ramon y Cajal (1852-1934) is considered to be one of the founders of the field of
      neuroscience. In 1911, he described interstitial neurons in the gut, noting that
      they were primitive accessory components that perhaps modify smooth muscle
      contraction, themselves subject to regulation from principle neurons. The
      accuracy of his description of their appearance and activities has led to these
      cells now being called the interstitial cells of Cajal (ICC). Thuneberg and
      Faussone-Pellegrini were instrumental in bringing these cells to the attention of
      gastroenterologists and pathologists in the early 1980s. Subsequently, the
      development of antibodies to c-kit has allowed routine identification of the ICC
      in pathology specimens. c-Kit is a transmembrane protein kinase which has as
      ligand stem cell factor and is involved in cell development in a variety of cell
      lineages. In the gut musculature, ICC and mast cells are the only cells that have
      prominent c-kit expression. The ICC are now known to play an important role in
      gut motility and absent or disordered ICC networks have been identified in a
      variety of motility disorders.

PMID- 17222247
TI  - Interstitial cells of Cajal in health and disease. Part II: ICC and
      gastrointestinal stromal tumours.
AB  - Mesenchymal tumours in the gastrointestinal tract have long been problematic in
      terms of diagnosis, prognosis and therapy, but recent advances in
      immunohistochemistry and related therapies have allowed more specific diagnosis.
      In particular, the recognition that both the interstitial cells of Cajal (ICC)
      and many gastrointestinal stromal tumours (GISTs) are positive for c-kit and CD34
      and have other features similar to those of ICC has led to the use of imatinib, a
      novel small molecule therapy that blocks the CD117/c-kit tyrosine kinase
      receptor, which shows remarkable efficacy in treatment of malignant and
      metastatic GISTs as well as other malignancies.

PMID- 17222248
TI  - Association of COX-2 expression with corresponding active and chronic
      inflammatory reactions in Barrett's metaplasia and progression to cancer.
AB  - AIMS: Risk reduction for Barrett's cancer in individuals taking non-steroidal
      anti-inflammatory drugs has been reported. Cyclooxygenase (COX)-2, one of the
      inhibited enzymes, is putatively involved in Barrett's cancer pathogenesis. The
      aim of this study was to examine a possible association between COX-2 protein
      expression and the development and progression of the Barrett's metaplasia
      dysplasia-carcinoma sequence and the type and degree of associated inflammatory
      reaction. METHODS AND RESULTS: Squamous epithelium, metaplastic, low-grade, high
      grade dysplastic lesions and tumour tissue of 49 resection specimens from
      patients with Barrett's adenocarcinoma were immunohistochemically analysed.
      Active and chronic inflammatory reactions were classified according to the
      Updated Sydney System. Within the Barrett's sequence, a significant progressive
      increase in COX-2 expression was identified (P < 0.0001). The most significant
      differences were detected between squamous epithelium and Barrett's metaplasia (P
      < 0.001) and from low- to high-grade dysplasia (P < 0.0001). Active and chronic
      inflammation were significantly different between squamous epithelium and
      Barrett's metaplasia (P < 0.0001), but not during further progression in the
      sequence. CONCLUSIONS: Increasing COX-2 expression in Barrett's metaplasia is
      significantly associated with a change in the local inflammatory reaction, but
      not during further progression through dysplasia to cancer. This supports the
      potential of a chemoprevention strategy using COX-2 inhibitors independent of the
      extent and type of the inflammatory reaction in Barrett's oesophagus.

PMID- 17222249
TI  - Immunohistochemical variability of epidermal growth factor receptor (EGFR) in
      liver metastases from colonic carcinomas.
AB  - AIMS: To follow and compare immunohistochemical expression of epidermal growth
      factor receptor (EGFR) in tumour cells during the entire natural history of
      colonic carcinoma, from primary tumour to paired lymph node and sequentially
      resected liver metastases; and to test interobserver reproducibility of EGFR
      analysis. METHODS AND RESULTS: Forty patients had resection of colonic
      adenocarcinoma (27 with metastatic lymph nodes) and at least one partial
      hepatectomy (PH) for liver metastases; a second and a third PH were performed,
      respectively, in 14 and three patients; seven patients had tumour liver biopsy.
      EGFR immunohistochemistry (n = 130) was analysed independently by two
      pathologists. EGFR expression (membranous staining detected in > or = 1% of
      tumour cells) was detected in 38/40 colonic carcinomas, 23/26 lymph nodes and
      51/64 liver metastases. Both primary tumours and related metastases were EGFR+ in
      28 patients (73%). Discrepancies were found in EGFR status between liver and
      lymph node (23%) and among the different liver samples (31%). Interobserver
      agreement was very good (intraclass correlation coefficients of 0.81, 0.91 and
      0.85, respectively, for interpretation of staining in colon, lymph node and liver
      metastases). CONCLUSIONS: Since immunohistochemical detection of EGFR remains a
      prerequisite for EGFR-targeted therapy eligibility, different tumour samples
      should be tested to allow every patient a chance to take advantage of this
      treatment.

PMID- 17222250
TI  - Cytogenetic abnormalities in MALT lymphomas and their precursor lesions from
      different organs. A fluorescence in situ hybridization (FISH) study.
AB  - AIMS: To analyse the possible activation of distinct molecular pathways in mucosa
      associated lymphoid tissue (MALT) lymphoma, we determined the prevalence of
      trisomies 3, 12, 18 in MALT lymphomas from different organs, as well as the
      prevalence of translocations of the MALT1 gene in a subset of primary breast MALT
      lymphomas. We compared the numerical cytogenetic alterations in lymphomas,
      precursor lesions and in normal non-haematolymphoid tissue from the same organs.
      METHODS AND RESULTS: Forty-two samples of paraffin-embedded tissue (29 MALT
      lymphomas from stomach, breast, parotid and thyroid; two Sjogren's syndrome; two
      Hashimoto's thyroiditis and nine reactive samples) were studied by fluorescence
      in situ hybridization (FISH). Analysed together, the cases of gastric, parotid
      and thyroid MALT lymphomas presented trisomy 3 in 46%, trisomy 12 in 28% and
      trisomy 18 in 21% of the cases. In contrast to other locations, trisomy 3 was not
      present in the majority of the cases of primary breast MALT lymphomas. None of
      the nine breast cases presented MALT1 gene rearrangements. Half of the cases of
      preneoplastic lesions exhibited trisomy 3 and trisomy 12; none exhibited trisomy
      18. CONCLUSIONS: Trisomy 3 is the most frequent numerical abnormality in gastric,
      parotid and thyroid but not in primary breast MALT lymphomas. MALT1 gene
      rearrangements are also rare in this location, suggesting that distinct molecular
      pathways may be activated in breast cases.

PMID- 17222252
TI  - Whole-specimen histopathology: a method to produce whole-mount breast serial
      sections for 3-D digital histopathology imaging.
AB  - AIMS: To develop a method for preparing diagnostic-quality, whole-mount serial
      sections of breast specimens while preserving 3-D conformation. This required
      supporting the fresh specimen prior to breadloafing and refining the conventional
      tissue processing method. The overall goal is to use digital images of whole
      specimen histopathology to improve the estimation of extent of disease. METHODS
      AND RESULTS: To maintain a 3-D conformation, the specimen is suspended in 3.5%
      agar at 55 degrees C. The block is sliced at 5-mm intervals. Sectioning is
      performed after extended fixation in 4% formaldehyde from paraformaldehyde in 0.1
      m Millonig's buffer, followed by paraffin processing using a non-routine schedule
      and extended paraffin infiltration. Whole-mount serial breast sections are
      produced with features of equal or superior quality to that which can be achieved
      using conventional methods. The method is compatible with some
      immunohistochemical stains but requires further optimization for others.
      CONCLUSIONS: The technique is currently suitable for research applications. With
      the reduction in processing time achievable with microwave-assisted processing,
      there is the potential for its use as a routine clinical method. This tool may
      improve the accuracy of margin estimates and identification of multifocality in
      breast cancer; further evaluation is necessary.

PMID- 17222251
TI  - Clinical significance of RET/PTC and p53 protein expression in sporadic papillary
      thyroid carcinoma.
AB  - AIMS: Rearranged during Transfection (RET)/papillary thyroid carcinoma (PTC) and
      p53 are two genes involved in the pathogenesis of PTC. It has been suggested that
      RET/PTC expression is associated with higher rates of local extension and lymph
      node involvement, whereas p53 mutations are more frequent in poorly
      differentiated and anaplastic carcinomas. In addition, experimental studies have
      shown that p53 activity can modify the behaviour of PTC carrying RET/PTC. The aim
      of this study was to investigate the expression of both RET/PTC and p53 in order
      to evaluate their usefulness as prognostic factors. METHODS AND RESULTS: Resected
      specimens of 61 cases of PTC were studied immunohistochemically using a
      polyclonal antibody to RET and a monoclonal antibody to p53 protein. RET/PTC
      expression was associated with extrathyroid extension of PTC, at diagnosis (P <
      0.05). In contrast, no relationship between p53 immunoreactivity and clinical
      status was found. In addition, p53 expression was more prevalent among RET/PTC+
      patients, and significantly influenced the relationship observed between RET/PTC
      and extrathyroid extension of the disease. CONCLUSION: Our results suggest that
      immunohistochemistry for both PTC/RET and p53 could be useful in the clinical
      evaluation of patients with PTC.

PMID- 17222253
TI  - Heterogeneous expression of alpha-methylacyl-CoA racemase in prostatic cancer
      correlates with Gleason score.
AB  - AIMS: Alpha-methylacyl-CoA racemase (AMACR) is a sensitive and specific
      immunohistochemical marker of prostatic malignancy, staining 80-100% of prostatic
      cancers with absent staining in benign glands. However, positive staining in
      benign conditions as well as low rates of AMACR reactivity in prostatic cancer
      variants have been described. Preliminary use of AMACR immunohistochemistry in
      our institution has suggested lower specificity and sensitivity for prostatic
      cancer than initially proposed. The aim of this study was to establish true rates
      of AMACR reactivity in prostatic cancer and benign prostatic hyperplasia (BPH).
      METHODS AND RESULTS: AMACR immunohistochemistry was performed on sections from 57
      prostatic cancers and 44 BPH resections. Ninety-one percent of cancers were
      AMACR+, with diffuse (> 75%) tumour staining in 53% of cases. Thirty-eight
      percent of tumours showed heterogeneous expression (1-75% tumour staining). This
      was significantly correlated with increased Gleason score. High-grade prostatic
      intraepithelial neoplasia (PIN) was AMACR+ in 87% of cancers. Eleven percent of
      BPH showed moderate or strong staining in benign glands, focally mimicking the
      malignant staining pattern. CONCLUSIONS: This study confirms heterogeneous AMACR
      expression in prostatic cancer and shows a correlation with Gleason score.
      Positive staining in BPH is also documented, thus emphasizing the importance of
      interpreting AMACR immunohistochemistry in the context of other findings in a
      diagnostic setting.

PMID- 17222254
TI  - Chromosomal imbalances and NF2 mutational analysis in a series of 10 spinal nerve
      sheath myxomas.
AB  - AIMS: To report the demographic, clinical and molecular profile of a series of
      intraspinal nerve sheath myxomas. Nerve sheath myxomas are diagnostically
      challenging, mainly cutaneous spindle cell neoplasms exhibiting Schwann cell
      differentiation. They are frequently mistaken for neurothekeomas and their
      genetic features are essentially unknown. METHODS AND RESULTS: Ten spinal nerve
      sheath myxomas with a preferential location in the lumbar spine (70%) were
      investigated. Presenting symptoms consisted of sciatic pain (100%), muscle
      weakness and paraesthesia (60% each). Intraoperatively, all tumours were attached
      to a spinal nerve. Chromosomal imbalances by comparative genomic hybridization
      were found in 8/10 cases, consisting of -22q (80%) and -19 (30%). Polymerase
      chain reaction analysis of the NF2 gene (exons 1-16) revealed two tumours with
      mutations in exon 8 and 14, respectively. CONCLUSIONS: Although these 10 nerve
      sheath myxomas exhibited Schwann cell differentiation and frequently showed loss
      of chromosome 22q typically encountered in peripheral nerve tumours, only two
      cases demonstrated mutations of the NF2 gene. This may indicate involvement of
      other tumour suppressor genes on 22q in nerve sheath myxomas and shows that they
      are more closely related at the molecular level to sporadic schwannomas,
      underscoring the presumption that they are true nerve sheath tumours.

PMID- 17222255
TI  - Organizing pneumonia and lymphoplasmacytic inflammation predict treatment
      response in idiopathic pulmonary fibrosis.
AB  - AIMS: To identify individual histopathological features within usual interstitial
      pneumonia pattern that predict responsiveness to immunosuppressive therapy.
      METHODS AND RESULTS: Fifty-six retrospectively confirmed usual interstitial
      pneumonia pattern surgical lung biopsy specimens from subjects with idiopathic
      pulmonary fibrosis treated with corticosteroid and cytotoxic therapy were
      included. Eleven prospectively defined histopathological features were evaluated
      by two expert pulmonary pathologists. Regression analysis identified predictors
      of response to therapy, as defined by the change in percent predicted forced
      vital capacity over 6 months. Additional end-points were change in dyspnoea score
      over 6 months, and survival time. Improvement in percent predicted forced vital
      capacity was associated with lymphoplasmacytic inflammation, while worsening of
      percent predicted forced vital capacity was associated with the presence of
      organizing pneumonia and fibroblast foci. Worsening dyspnoea was associated with
      fibroblast foci. Survival time was associated with age and baseline percent
      predicted forced vital capacity, but not with any individual histopathological
      feature. CONCLUSIONS: In pathological usual interstitial pneumonia pattern, the
      presence of lymphoplasmacytic inflammation predicts responsiveness to
      immunomodulatory therapy, while airspace organization predicts lack of response.

PMID- 17222256
TI  - A randomized controlled trial of the diagnostic accuracy of internet-based
      telepathology compared with conventional microscopy.
AB  - AIMS: To compare the diagnostic accuracy of internet-based virtual microscopy
      with conventional light microscopy, in the context of renal biopsies assessed by
      participants in the UK National Renal Pathology External Quality Assessment (EQA)
      Scheme. METHODS AND RESULTS: 'Virtual slides' of current EQA cases were made
      available over the internet to participants in the scheme. The approach permitted
      what may reasonably be described as a randomized controlled trial of the
      diagnostic accuracy of this mode of telepathology, in the context of renal
      pathology. No significant difference in diagnostic accuracy could be detected
      between the diagnoses proffered on the basis of virtual slides and conventional
      slides; but using virtual slides took pathologists considerably longer.
      CONCLUSIONS: This result provides some encouragement for the implementation of
      such virtual slide-based telepathology systems. However, in failing to detect a
      difference, equivalence of diagnostic accuracy has not been proved; nor has the
      relevance of this result to other fields of histopathology been demonstrated. A
      decision to implement a diagnostic telepathology system requires consideration of
      numerous factors beyond diagnostic accuracy, including financial, legal,
      professional and ethical issues.

PMID- 17222258
TI  - The relationship between cytokeratin expression in bladder washings and resected
      tumour specimens.

PMID- 17222259
TI  - Inflammatory myofibroblastic tumour of the bladder may express anaplastic
      lymphoma kinase by translocation-dependent and translocation-independent
      mechanisms: a report of two cases.

PMID- 17222260
TI  - Differential expression of adhesion molecules in lung tumours.

PMID- 17222261
TI  - Apoptotic markers in the differential diagnosis of keratoacanthoma versus
      squamous cell carcinoma.

PMID- 17222262
TI  - Eye protection during microscopy in histopathology: a simple and effective
      method.

PMID- 17222264
TI  - The implications of recent findings on the link between cannabis and psychosis.

PMID- 17222265
TI  - A hard act to follow: assessing the consequences of licensing reform in England
      and Wales.

PMID- 17222266
TI  - Denicotinized cigarettes: a new tool to combat cigarette addiction?

PMID- 17222267
TI  - Viewing videotapes of one's own delirium tremens: renaissance of alcohol
      dependence as 'disease of the will'?

PMID- 17222268
TI  - Road to alcohol dependence: a commentary on Sartor et al. (2007).

PMID- 17222269
TI  - An important new phenotype and some next-step questions: commentary on Sartor et
      al. (2007).

PMID- 17222270
TI  - Early drinking and the development of alcoholism: a commentary on Sartor et al.
      (2007).

PMID- 17222273
TI  - Conversation with Hamid Ghodse: interview by Addiction.

PMID- 17222272
TI  - The Australasian Professional Society on Alcohol and Other Drugs: from a cottage
      industry to a regional player.

PMID- 17222274
TI  - Staff attitudes towards working with drug users: development of the Drug Problems
      Perceptions Questionnaire.
AB  - AIM: To evaluate the psychometric properties of an adaptation of the Alcohol and
      Alcohol Problems Perceptions Questionnaire to measure the attitudes of staff to
      working with drug users (the DDPPQ). DESIGN: Postal survey: a questionnaire was
      mailed to participants on two occasions. SETTING: A large urban National Health
      Service (NHS) mental health service. PARTICIPANTS: A stratified random sample of
      medical staff, clinical psychologists, occupational therapists and nurses (n =
      672) who work within generic mental health, adolescent psychiatry, forensic
      psychiatry and alcohol and drug services. Response rate at Time 1 was 56% and 68%
      at Time 2. MEASUREMENTS: A structured demographic questionnaire; individual item
      and total scores for the DDPPQ administered on two occasions 4 weeks apart; data
      relating to the content validity of the instrument. FINDINGS: A principal
      component analysis confirmed the DDPPQ's construct validity and participants
      confirmed its content validity. Following analysis of the instrument's test
      retest reliability and its principal component structure it was reduced to a 20
      item scale. Its five subscales related to role adequacy, role support, job
      satisfaction, role-specific self-esteem and role legitimacy. CONCLUSION: The
      refined DDPPQ was shown to be a valid and reliable tool which can be used to
      measure attitudes of people in relation to working with drug users.

PMID- 17222276
TI  - Viewing videotape of themselves while experiencing delirium tremens could reduce
      the relapse rate in alcohol-dependent patients.
AB  - AIMS: The aim of this prospective randomized controlled study was to determine
      whether viewing videotape of themselves while experiencing delirium tremens (DT)
      reduces the relapse rate in alcohol-dependent patients. Our hypothesis about the
      efficacy of videotapes exposure to DT is consistent with a cognitive behavior
      model. DESIGN: Sixty patients with DT and a minimum of 3 years of severe alcohol
      dependence [Diagnostic and Statistical Manual version IV (DSM-IV criteria] were
      included in this study. Patients were videotaped during the acute phase of DT and
      randomized into two groups: group A patients received individual exposure to
      their videotape and an explanation of the symptoms by a psychiatrist; and control
      group B patients, who were without videotape experience. Both groups received the
      same treatment during the acute and the maintenance phases, without aversive
      therapy or psychotherapy. The two groups did not differ significantly in number
      of drinks per day prior to admission, age, marital status, social environment,
      education, professional and financial status or family psychiatric history.
      SETTING: An in-patient crisis unit for patients with alcohol dependence.
      MEASUREMENTS: All patients were observed for 6 months during monthly visits.
      Outcomes included relapse, drinking days per week and number of drinks per
      drinking day. All patients and their families signed informed consent. FINDINGS:
      The patients with videotape experience had a significantly lower relapse rate
      after the first month (0% versus 20%), 2 months (13.33% versus 46.67%) and 3
      months (26.67% versus 53.33%). Patients with videotape experience had less severe
      relapses and consumed fewer units of alcohol than controls. CONCLUSIONS:
      Videotape exposure in delirium tremens is an original therapeutic method which
      seems to be effective in reducing relapse risk in patients with alcohol
      dependence.

PMID- 17222275
TI  - The role of childhood risk factors in initiation of alcohol use and progression
      to alcohol dependence.
AB  - AIMS: To identify childhood risk factors that predict (a) age of first drink and
      (b) time from first use to alcohol dependence (AD) onset, using survival
      analysis. PARTICIPANTS: The sample consisted of 1269 offspring (mean age = 20.1
      years) of male twins from the Vietnam Era Twin Registry; 46.2% were offspring of
      alcohol-dependent fathers. MEASUREMENTS: DSM-IV psychiatric diagnoses and
      substance use behaviors were assessed by structured telephone interview.
      FINDINGS: First drink occurred on average at 15.7 years; AD onset at 19.1 years.
      A Cox proportional hazard regression analysis revealed conduct disorder (CD) as
      the most potent predictor of early alcohol initiation (HR 2.48; CI 1.85-3.32).
      Attention deficit hyperactivity disorder (ADHD), maternal AD, paternal AD, male
      gender and parental divorce were also associated with early first use (HR 1.20
      1.52; CI 1.04-1.39-1.18-1.96). A Cox proportional hazard regression analysis
      modeling first drink to AD identified nicotine dependence (HR 3.91; CI 2.48-6.17)
      and generalized anxiety disorder (GAD) (HR 3.45; CI 2.08-5.72) as robust
      predictors of progression to AD. CD (HR 1.75; CI 1.10-2.77) and cannabis abuse
      (HR 1.88; CI 1.22-2.90) were also associated with rapid transition to AD.
      CONCLUSIONS: Results highlight the role of psychiatric and substance use
      disorders in progression from first drink to AD, underscore the continuity of
      risk associated with CD and indicate that (with the exception of CD) different
      factors play a role in transition to AD than in initiation of alcohol use.
      Distinctions between stages are interpreted in a developmental framework.

PMID- 17222277
TI  - Theory of mind, humour processing and executive functioning in alcoholism.
AB  - AIMS: Alcoholism is associated with cognitive deficits, which have been
      interpreted in terms of a specific vulnerability of the frontal lobes to the
      toxic effects of alcohol. While executive functions in alcoholism have been
      investigated extensively, only little work has been carried out on social
      cognition. The aim of the present study was to investigate the association
      between executive functions, theory of mind and humour processing in alcoholism.
      DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: A comprehensive
      neuropsychological test battery was administered to 29 alcoholic patients (Alc)
      and 29 healthy controls (HC). The test battery included measurements of affect,
      general intellectual abilities, executive functions, humour processing and theory
      of mind. The two groups were comparable with respect to affective variables, IQ,
      gender and age. FINDINGS AND CONCLUSIONS: Group comparisons revealed cognitive as
      well as affective humour processing deficits of alcoholics in comparison with HC.
      The observed impairments were related to theory of mind and executive functions.
      The deficits may contribute to interpersonal problems and are thus of relevance
      to rehabilitation.

PMID- 17222278
TI  - Controlled study of brief personalized assessment-feedback for drinkers
      interested in self-help.
AB  - AIMS: Brief alcohol interventions typically have been directed to heavy-drinking
      patients seeking primary health care and college students. This study examined
      the efficacy of mailing brief personalized assessment-feedback to interested
      drinkers recruited from the general public. We hypothesized that problem drinkers
      would benefit more from the intervention than individuals who were not problem
      drinkers. DESIGN: A two-arm, double-blinded, community-based randomized
      controlled trial with 6-month follow-up. SETTING AND PARTICIPANTS: A screening
      interview was administered to a stratified random sample of 10 014 Canadians 18
      years of age and older (5621 women and 4393 men; M age = 43.3 years, SD = 15.99;
      response rate = 65.4%). INTERVENTION: Current drinkers interested in receiving
      alcohol self-help materials (n = 1727) were assigned randomly to receive brief
      personalized assessment-feedback on male and female population drinking norms by
      mail, or to a delayed-treatment control group, and were contacted 6 months later
      (76% retention rate). MEASUREMENTS: Problem drinking status at baseline [using
      sex-specific Alcohol Use Disorders Identification Test (AUDIT) cut scores], and
      frequency and quantity of alcohol use at follow-up. FINDINGS: Analysis of
      covariance identified the hypothesized interaction of baseline problem drinking
      status and treatment condition (P < 0.01). Among problem drinkers identified at
      baseline the intervention caused a 10.1% reduction in per-occasion binge drinking
      compared to controls, whereas there was no difference in binge drinking across
      conditions for non-problem drinkers. CONCLUSIONS: The continuum of care for
      alcohol problems can be broadened by providing brief interventions to interested
      drinkers in the general population.

PMID- 17222279
TI  - Do alcohol restrictions reduce suicide mortality?
AB  - AIM: Blood alcohol concentration (BAC) at the time of suicide was examined in
      relation to the marked falls in suicide rates and per capita alcohol consumption
      in Estonia during the major Soviet anti-alcohol campaign from 1 June 1985. DESIGN
      AND PARTICIPANTS: In all, 5054 suicide cases (76% males, 24% females) were
      examined with respect to the official autopsy reports of the Estonian Bureau of
      Forensic Medicine (autopsy rates: 95% of males, 88% of females) before (1981-84),
      during (1986-88) and after (1989-92) the campaign. Cases were divided by gender
      and BAC level (0.5-1.49, 1.5-2.49 and > 2.5 per thousand). FINDINGS: During the
      campaign, annual per capita alcohol consumption in Estonia fell from 10.9 to 6.6
      l. Alcohol in blood was found in 47.9% before, 35.1% during and 40.9% after the
      campaign. During the intervention, BAC-positive, i.e. alcohol-positive, suicides
      decreased by 39.2% for males and 41.4% for females, with the largest fall
      occurring at the BAC 2.5 per thousand + level for both sexes. Changes in BAC
      negative suicides were modest. When the campaign ended suicide rates started to
      rise. CONCLUSIONS: Investigation on an individual level showed that alcohol
      consumption was a common precursor to suicide and that rigorous alcohol
      restrictions were accompanied particularly by a decrease in BAC-positive suicide
      mortality among both sexes. However, the 'natural experiment' does not, in terms
      of study design, demonstrate convincingly that the fall in the suicide rate was
      due specifically to the decrease in alcohol use as such.

PMID- 17222280
TI  - Excessive alcohol consumption is associated with reduced quality of life among
      methadone patients.
AB  - AIM: To evaluate the impact of excessive alcohol consumption on the health
      related quality of life of patients receiving methadone treatment for opioid
      dependence. DESIGN: A cross-sectional survey. PARTICIPANTS: One hundred and
      ninety-two patients attending out-patient methadone clinics in the south-east of
      England, United Kingdom. MEASUREMENTS: Quality of life (QoL) was assessed using
      the Medical Outcomes Study: General Health Survey, Short Form (SF-12). Alcohol
      consumption was assessed using the Alcohol Use Disorders Identification Test
      (AUDIT). FINDINGS: Approximately one-third of the sample (57/192) were AUDIT
      positive (score > or = 8) and 20 of the 135 AUDIT-negative patients reported past
      history of alcohol problems. AUDIT-positive patients were less satisfied with
      their methadone dose than AUDIT-negative patients (P = 0.002), despite having a
      higher dose. AUDIT-positive patients reported more physical (P = 0.020) and
      psychological (P = 0.034) health problems and poorer QoL (P = 0.008) with an
      estimated effect size of 0.46. Lower QoL scores for AUDIT-positive patients
      affected both 'physical' (P = 0.009) and 'psychological' (P = 0.012) health
      domains with poor role functioning ('role limitation' due to physical health, P <
      0.001 and to emotional health, P = 0.009), social functioning (P = 0.015) and
      self-perceived general health (P = 0.029). CONCLUSION: Excessive alcohol
      consumption may be associated with a distinctive pattern of QoL impairment in
      methadone patients. In addition to advising methadone patients regarding their
      alcohol consumption, comprehensive care plans should seek to restore normal
      personal, family and social role functioning through the provision of appropriate
      health and social care.

PMID- 17222281
TI  - Methadone in pregnancy: treatment retention and neonatal outcomes.
AB  - AIM: To examine the association between retention in methadone treatment during
      pregnancy and key neonatal outcomes. DESIGN: Client data from the New South Wales
      Pharmaceutical Drugs of Addiction System was linked to birth information from the
      NSW Midwives Data Collection and the NSW Inpatient Statistics Collection from
      1992 to 2002. MEASUREMENTS: Obstetric and perinatal characteristics of women who
      were retained continuously on methadone maintenance throughout their pregnancy
      were compared to those who entered late in their pregnancies (less than 6 months
      prior to birth) and those whose last treatment episode ended at least 1 year
      prior to birth. FINDINGS: There were 2993 births to women recorded as being on
      methadone at delivery, increasing from 62 in 1992 to 459 births in 2002. Compared
      to mothers who were maintained continuously on methadone throughout their
      pregnancy, those who entered treatment late also presented later to antenatal
      services, were more likely to arrive at hospital for delivery unbooked, were more
      often unmarried, indigenous and smoked more heavily. A higher proportion of
      neonates born to late entrants were born at less than 37 weeks gestation and were
      admitted to special care nursery more often. CONCLUSION: Continuous methadone
      treatment during pregnancy is associated with earlier antenatal care and improved
      neonatal outcomes. Innovative techniques for early engagement in methadone
      treatment by pregnant heroin using women or those planning to become pregnant
      should be identified and implemented.

PMID- 17222282
TI  - Effects of varying the monetary value of voucher-based incentives on abstinence
      achieved during and following treatment among cocaine-dependent outpatients.
AB  - AIMS: This study examined whether increasing the amount of abstinence achieved
      during outpatient treatment for cocaine dependence is an effective method for
      increasing longer-term cocaine abstinence. DESIGN: A two-condition, parallel
      groups, randomized controlled trial was conducted. SETTING: The trial was
      conducted in a university-based research clinic. PARTICIPANTS: A total of 100
      cocaine-dependent outpatients participated in the trial. INTERVENTION:
      Participants were assigned randomly to receive treatment based on the community
      reinforcement approach (CRA) plus voucher-based incentives set at a relatively
      high monetary value (maximal value = $1995/12 weeks) or CRA with vouchers set at
      a relatively low monetary value (maximal value = $499/12 weeks). Vouchers were
      earned contingent on cocaine-negative urinalysis results during the initial 12
      weeks of the 24-week outpatient treatment. MEASUREMENTS: Outcomes were evaluated
      using urine-toxicology testing, questionnaires and other self-report instruments.
      FINDINGS: Increasing voucher value increased the duration of continuous cocaine
      abstinence achieved during the 24-week treatment period. Point-prevalence cocaine
      abstinence assessed every 3 months throughout an 18-month follow-up period was
      greater in the high- than low-value voucher conditions. The duration of
      abstinence achieved during treatment predicted abstinence during follow-up,
      although that relationship weakened over time. CONCLUSIONS: Increasing the value
      of abstinence-contingent incentives during the initial weeks of treatment appears
      to represent an effective method for increasing during-treatment and longer-term
      cocaine abstinence, but the positive association of during-treatment abstinence
      with longer-term outcome dissipates with time.

PMID- 17222283
TI  - A database on treating drug addiction with traditional Chinese medicine.
AB  - AIMS: Traditional Chinese medicine (TCM) has been used to treat drug addiction
      for more than 160 years and valuable experiences have been accumulated with
      regard to patients' detoxification and rehabilitation. The aims of this project
      were (1) to establish a computerized, bilingual (Chinese-English) database on TCM
      for drug addiction; (2) to analyse the literature published in this field; and
      (3) to identify those Chinese herbs commonly used for drug addiction treatment.
      DESIGN: (1) Paper collection: related papers were collected through electronic
      databases and hand-searched materials; (2) data computerization: the Microsoft
      Access program and Delphi language were used as the major data management
      systems; (3) paper analysis: annual publications from 1989 to 2003 were
      classified and calculated; and (4) herbal analysis: the frequency of herbs used
      and herbal function categories were analysed. FINDINGS: (1) A special bilingual
      database that contained 340 works of professional literature, including 85 patent
      files on TCM for drug addiction, was established, in which more than 90% of the
      publications originated from mainland China; (2) the literature classification
      showed a significant increase in the number of publications on clinical and
      laboratory researches in this field over the past decade; (3) five functional
      categorizations of Chinese herbs and the 10 most frequently used Chinese herbs as
      well as three toxic herbs were identified from more than 200 herbs reported in
      150 original research articles and 85 patent files. CONCLUSIONS: For the first
      time, the published data on TCM in the treatment of drug addiction were analysed
      systematically by using a new database. The results are invaluable for further
      laboratory and clinical studies to obtain more direct evidence.

PMID- 17222284
TI  - Corrected-QT intervals as related to methadone dose and serum level in methadone
      maintenance treatment (MMT) patients: a cross-sectional study.
AB  - AIMS: To determine and evaluate QTc intervals in electrocardiograms (ECGs) of
      former heroin addicts, currently in methadone maintenance treatment (MMT), as
      previous reports suggest that methadone may prolong QTc intervals, thus possibly
      increasing the risk for Torsade de pointes (TdP). DESIGN: Cross-sectional study.
      SETTING: Between January 2003 and September 2004, patients on a steady dose of
      methadone for at least 2 weeks were studied. PARTICIPANTS: This study is a subset
      of 153 patients, of whom 151 patients participated in a study of high methadone
      doses and serum levels. A total of 138 patients in MMT for a minimum of 100 days
      up to 10.7 years, receiving 40-290 mg/day methadone dose, participated.
      MEASUREMENTS: Patients had an ECG at the time when blood was drawn for
      determination of serum methadone levels at around 24 hours after the last oral
      methadone dose. Corrected-QT intervals (QTc) were calculated using the Bazett
      formula. FINDINGS: Of 138 patients studied, 98 (71%) were male. Mean QTc interval
      was 418.3 +/- 32.8 milliseconds (ms). Mean methadone dose was 170.9 +/- 50.3
      mg/day and mean serum methadone level was 708.2 +/- 363.1 ng/ml. Methadone dose
      and serum levels did not correlate with QTc. Three patients had QTc intervals
      above 500 ms ('prolonged'). After 2 +/- 0.4 years of follow-up, two patients
      died; they were two of three patients with very prolonged QTc. Causes of death
      were not attributed to cardiac origin. An additional 19 patients had QTc
      intervals of between 450 and 499 ms ('possibly prolonged'). None of these QTc >
      or = 450 ms patients had any cardiac problems. Methadone doses of all 22 patients
      were > 120 mg/day. CONCLUSIONS: Methadone maintenance is generally safe; however,
      the possible toxicity of high dose (> 120 mg/day) should be monitored for QTc.

PMID- 17222285
TI  - Readiness for change and drug use outcomes after treatment.
AB  - AIMS: The present study represents the first large-scale test of the capacity to
      predict illicit drug treatment outcomes of an instrument [Stages of Change and
      Treatment Eagerness Scale (SOCRATES)] purporting to measure processes underlying
      stages of change. The main hypothesis was that 'taking steps' should be
      predictive of less frequent use of illicit opiates (heroin and non-prescribed
      methadone) at follow-up. DESIGN: The sample comprised 1075 people seeking
      treatment for drug abuse problems in 54 treatment agencies in England. The study
      uses a longitudinal, prospective cohort design. Structured interviews were
      conducted at treatment intake and at 1-year follow-up. Data were collected about
      illicit drug use (frequency of use of heroin, non-prescribed methadone, cocaine
      and amphetamines, and non-prescribed benzodiazepines) and other problems.
      FINDINGS: Results failed to support the hypothesis that taking steps should be
      associated with less frequent use of illicit opiates at follow-up. No
      statistically significant associations of any kind were found between readiness
      for change measures and use of opiates or stimulants at follow-up. A negative
      association was found between taking steps and benzodiazepine misuse. Readiness
      for change measures were correlated with heroin use and psychiatric symptom
      scores at treatment intake. CONCLUSIONS: Readiness for change measures were not
      associated with illicit drug use outcomes. Of the 12 hypothesized relationships
      between readiness for change measures and outcomes, our results show only one
      'hit' and 11 'misses'.

PMID- 17222286
TI  - What do we get for our money? Cost-effectiveness of adding contingency
      management.
AB  - AIMS: To assess the relative cost-effectiveness of lower versus higher cost prize
      based contingency management (CM) treatments for cocaine abuse. DESIGN: Cost
      effectiveness analyses based on resource utilization, unit costs and outcomes
      from a previous CM efficacy trial. SETTING: Two community-based treatment
      centers. PARTICIPANTS: Patients (n = 120) enrolled in out-patient treatment for
      cocaine abuse. INTERVENTION: Random assignment to one of three 12-week treatment
      conditions: standard treatment (STD) alone or two variants of STD combined with
      prize based CM. In CM, drawing for prizes was available to those submitting drug
      free urine samples and completing goal-related activities. There were two levels
      of pay-out (referred to as $80 versus $240) based on the potential value of
      prizes won. MEASUREMENTS: Costs per participant associated with counseling
      utilization, urine and breathalyzer testing, and operation of the prize-drawing
      procedure were derived from a survey conducted at 16 clinics that had
      participated in CM studies. The three measures of effectiveness were: (1) longest
      duration of consecutive abstinence; (2) percentage completing treatment; and (3)
      percentage of samples drug-free. FINDINGS: The higher magnitude CM produced
      outcomes at a lower per unit cost than did the lower magnitude prize CM
      treatment. This was the case for all three outcome measures examined and held
      across various assumptions in the sensitivity analysis. CONCLUSIONS: Cost
      effectiveness analyses can inform policy decisions regarding selection of one
      treatment model over another. Decisions on adoption of new evidence-based
      treatments would be aided by more information on society's willingness to pay for
      incremental gains in effectiveness.

PMID- 17222287
TI  - London audit of drug-related overdose deaths: characteristics and typology, and
      implications for prevention and monitoring.
AB  - OBJECTIVES: To describe the circumstances and draft a typology of drug-related
      overdose deaths. SETTING: London, 2003. METHODS: An audit of 148 drug overdose
      deaths (involving heroin, methadone, dihydrocodeine, cocaine, amphetamine or
      MDMA) investigated by coroners during 2003. Information extracted on toxicology,
      pathology and circumstances were used to identify drug(s) implicated in the
      death. RESULTS: Poly- or multiple drug use was detected in the majority of deaths
      with at least 69 different combinations, including 66% for heroin and 42% for
      cocaine. Six categories of death were identified involving an opiate (100, 68%);
      cocaine (14, 9%); other controlled drug (five, 3%); mixed drug overdose (18,
      12%); other prescribed drug (five, 3%); and other causes (seven, 5%). A witness
      was present and the death was not instantaneous in 92 (61%) cases, although
      evidence in the coronial file suggested that in the majority of cases the
      overdose went unnoticed until too late to intervene. In all, 15 (one in 10) of
      the deceased were released from prison within 3 months of death; and 37 (one in
      four) were reported as in receipt of a methadone prescription. CONCLUSIONS:
      Perhaps for the first time in the United Kingdom cocaine was detected in more
      drug overdose deaths than methadone. However, reducing heroin use is central to
      the prevention of drug-related deaths. We recommend that overdose prevention
      encompasses strategies to encourage a 'mutual duty of care' among problem drug
      users, and in the United Kingdom further investigation of the relationship of
      methadone treatment failures on overall trends in drug-related deaths is merited.

PMID- 17222289
TI  - Alcohol policy: who should sit at the table?

PMID- 17222288
TI  - Smoking in the absence of nicotine: behavioral, subjective and physiological
      effects over 11 days.
AB  - AIMS: Sensorimotor stimuli associated with tobacco smoking influence smoking
      behavior; however, current research has focused almost exclusively on the effects
      of brief, laboratory-based exposure to smoking-related stimuli. The purpose of
      this experiment was to characterize the effects of smoking stimuli delivered in
      the absence of nicotine over an extended (11-day) exposure. DESIGN, SETTING AND
      PARTICIPANTS: Thirty adult regular smokers participated in an in-patient study.
      After assessing preferred brand smoking, participants were assigned randomly to
      one of three groups corresponding to subsequent smoking conditions: nicotine
      containing cigarettes, de-nicotinized cigarettes or no smoking. MEASUREMENTS:
      Measures of smoking reinforcement, subjective effects, physiological effects,
      withdrawal/craving and puff topography were taken repeatedly during both periods
      of free access and controlled assessments during abstinence. FINDINGS: Daily de
      nicotinized cigarette use declined immediately by 1.7 cigarettes/day compared to
      the preferred brand baseline and declined by another 3.5 cigarettes over time;
      participants smoking de-nicotinized cigarettes also demonstrated a 31% decline in
      the number of puffs earned on a progressive ratio, a measure of the motivation to
      smoke, during the study. Subjective ratings of smoking were largely negative
      throughout the study in the de-nicotinized group, while the nicotine-containing
      condition reported increasingly positive subjective effects with repeated
      exposure. Acute craving suppression following smoking remained evident throughout
      the study regardless of nicotine content. CONCLUSIONS: These effects highlight
      the importance of non-nicotine sensorimotor stimuli as determinants of the
      maintenance of smoking behavior and suggests that extinction of conditioned
      reinforcement in the absence of nicotine progresses slowly.

PMID- 17222291
TI  - A comparison of the variability spectra of two genomic loci in a European group
      of individuals reveals fundamental differences pointing to selection or a
      population bottleneck.
AB  - Knowledge about the variability spectra of neutrally evolving sequences in a
      population is a prerequisite for the identification of genes, which may have been
      under positive selection during recent human evolution. Here, we report the
      results of a re-sequencing project of a presumably neutrally evolving chromosome
      22 locus with a severely reduced recombination frequency in a group of 24
      individuals of German origin. The comparison of these data with the results of a
      similar analysis of a chromosome 17 locus revealed striking differences, although
      the same group of individuals was used. For the chromosome 17 locus two well
      separated groups of sequences, a positive value of Tajima's D and a TMRCA of
      700,000 years were observed. In contrast, the sequences from the chromosome 22
      locus were found to be relatively homogeneous, with no deep splits between
      subgroups; the obtained value for Tajima's D was negative and the TMRCA was only
      260,000 years. These discrepancies may be explained by selection or demographic
      processes. Regarding demography, the most plausible explanation is the assumption
      of a severe bottleneck in the history of the European population: in the case of
      the chromosome 17 locus two ancient lineages passed this bottleneck; for the
      chromosome 22 locus it was only one ancient lineage.

PMID- 17222292
TI  - Common adiponectin gene variants show different effects on risk of cardiovascular
      disease and type 2 diabetes in European subjects.
AB  - Alterations in the secretion of adipokines may explain the link between obesity,
      type 2 diabetes (T2DM) and coronary artery disease (CAD). These conditions have
      been associated with variation in the adiponectin gene, although evidence for
      this relationship has been variable, with differences found even in similar
      samples. This study aims to clarify these inconsistencies by determining the
      impact of identified adiponectin gene (ADIPOQ) variants (-11391G>A,
      1377C>G[promoter] and +45T>G[exon 2] and +276G>T[intron 2]) on the prospective
      risk of CAD and T2DM in healthy men, and on adverse metabolic markers, in
      myocardial infarct survivors and controls from different parts of Europe. The
      hazard ratio for cardiovascular disease varied across the -11391GG/GA/AA(p =
      0.03) and -11371CC/CG/GG(p = 0.05) genotypes only. In contrast, only the +45T>G
      variant (3.80[1.76-8.24]) was associated with T2DM, while two haplotypes
      GCTT/GCGG (p < 0.05) and +276G>T(p = 0.01) increased risk in interaction with
      obesity. The variants were associated with a number of biomarkers in Southern but
      not Northern Europe (p = 0.01), despite no significant differences in allele or
      haplotype frequencies (p > 0.44). A risk haplotype could not be identified in
      either sample. Adiponectin gene variants are hence currently poor markers for the
      development of T2DM and CAD. Their influence on risk depends significantly on
      interactions that are not currently understood with either genetic variation
      elsewhere or the environment of the sample studied.

PMID- 17222293
TI  - Therapeutic options for Bowen's disease.
AB  - Multiple therapeutic options are available for treatment of Bowen's disease. The
      choice of therapy depends on clinical circumstance and medical practitioner
      experience. Newer therapies have more extensive support from the literature, but
      more established therapies may be preferred because of accessibility, cost and
      efficacy. An overview of the current therapeutic options for Bowen's disease is
      presented.

PMID- 17222294
TI  - Comparison of inpatient bed rest and home convalescence following split thickness
      skin grafting to the lower leg.
AB  - There has been a substantial move towards care of patients in an outpatient
      setting. This study was performed to determine if discharge home following split
      thickness skin grafting to the lower leg compromised graft results or morbidity
      compared with admission to hospital. Cases were reviewed retrospectively from the
      dermatology department's surgical records. All split thickness skin grafts to the
      lower legs over a 12-month period were included. All clinical notes were reviewed
      and phone calls made to patients and relatives. A total of 61 cases were
      included: 31 admitted as inpatients, 30 discharged home. There was no significant
      difference between the two groups' age, sex or comorbidities. A trend was seen in
      inpatients towards increased infection (P = 0.19) and venous thrombosis (P =
      0.34). There is a lack of significant difference between admitted and discharged
      patients in all outcomes including bleeding, number of dressing clinic follow ups
      and graft loss. These results suggest that home convalescence after split
      thickness skin grafting to the lower legs compares favourably with inpatient
      care.

PMID- 17222295
TI  - Retrospective review of primary melanomas excised at Waikato Hospital, New
      Zealand, 2002-2003.
AB  - The aim of this study was to review and compare melanomas referred by general
      practitioners and melanomas identified at specialist clinics. The medical records
      relating to 113 primary melanomas excised at Waikato Hospital (a specialist
      regional base hospital) during 2002 and 2003 were reviewed retrospectively. Forty
      seven melanomas (41%) were detected when patients attended specialist clinics
      (mainly plastic surgery and dermatology), and 66 melanomas (59%) were
      specifically referred by general practitioners. The melanomas detected at
      specialist clinics had a lower mean Breslow thickness than those referred by
      general practitioners (0.57 mm compared with 1.45 mm). Patients referred by
      general practitioners waited a mean of 26.5 days (range 0-94 days) for first
      specialist assessment. Following specialist assessment, patients waited a mean of
      24.2 days (0-81 days) before excision biopsy.

PMID- 17222296
TI  - Comparison of direct smear, culture and histology for the diagnosis of
      onychomycosis.
AB  - A sensitive and efficient diagnostic strategy is needed to confirm the clinical
      suspicion of onychomycosis. The purpose of this study was to compare the
      sensitivity of three most commonly used diagnostic methods for onychomycosis.
      Nail specimens of 96 patients with clinically suspected onychomycosis were
      evaluated using potassium hydroxide smear, culture and histology. A positive
      result of any of these tests was considered confirmatory for fungal infection and
      the sensitivity of each test as well as various combinations of them was
      calculated. The diagnosis of onychomycosis was confirmed in 47 patients (48.9%).
      Histology was the most sensitive single test for the diagnosis of onychomycosis,
      although its sensitivity (80.8%) was not statistically different from smear
      (76.5%). Both histology and smear were significantly more sensitive than culture
      (53.2%). The most sensitive combination of tests, smear plus histology, was 97.8%
      sensitive with 98% negative predictive value. In conclusion, direct smear
      combined with histological examination is the most sensitive diagnostic approach
      for onychomycosis.

PMID- 17222297
TI  - Dermatologist and family practitioner practice patterns for occupational contact
      dermatitis.
AB  - Medical practitioners have a role in the recognition of occupational contact
      dermatitis. The longer the duration of symptoms before diagnosis, the poorer the
      outcome. Our objective was to understand practice patterns, barriers and needs
      for early diagnosis of occupational contact dermatitis. A survey to obtain
      information on practice patterns was developed based on the literature and
      interviews with dermatologists and family practitioners. The survey was sent to
      all dermatologists and a random sample of 600 family practitioners in Ontario.
      Fifty-seven per cent of dermatologists and 9% of family practitioners report
      seeing more than 20 patients per year with occupational contact dermatitis. The
      majority of practitioners report taking a workplace exposure history. Barriers to
      taking a workplace exposure history include time constraints and lack of
      knowledge. Reasons for referral to specialists include a lack of expertise,
      testing facilities and knowledge about workers' compensation, time constraints
      and inadequate reimbursement, whereas lack of access to specialists is a barrier
      for referral. Although most practitioners identify a need for further education,
      a low volume of patients and time constraints are key barriers to continuing
      education. Opportunities are identified to improve educational initiatives and
      health services delivery for occupational contact dermatitis, tailored to each
      practitioner group.

PMID- 17222298
TI  - Clinical review of 202 patients with vulval lichen sclerosus: A possible
      association with psoriasis.
AB  - Two hundred and two patients with clinically typical or biopsy-confirmed vulval
      lichen sclerosus were reviewed either at consultation (75%) or by retrospectively
      examining their chart. At diagnosis, 79% were 50 years or older. Ninety-six per
      cent complained of itching, pain and/or dyspareunia. Lichen sclerosus most often
      affected the labia minora and perineum but 50% had perianal and 13% had
      extragenital disease. Thirty-five patients gave a history of psoriasis (17%),
      which affected the vulval area in 10. Thyroid disease was reported in 39 patients
      (19%), and 33 gave a family history of thyroid disease. Of those tested (142),
      20% had elevated thyroid antibodies. Topical clobetasol propionate was very
      effective but at least intermittent treatment was required long term in 85%. At
      follow up, 101 of 185 patients (56%) were asymptomatic but 22 (12%) continued to
      have moderate-to-severe symptoms. Thyroid disease and psoriasis are common
      associated conditions.

PMID- 17222299
TI  - Diffuse cutaneous leishmaniasis in an HIV-positive patient in western Africa.
AB  - A 36-year-old HIV1-positive woman presented with a 6-month history of a
      progressive papular and nodular eruption of the face and subsequent extensive
      spread to the rest of the skin. The diagnosis of diffuse cutaneous leishmaniasis
      was established by direct examination and skin biopsy. This atypical form had a
      dramatic improvement after a 21-day treatment with meglumine antimoniate. This
      clinical form may be confused with other endemic diseases in western Africa,
      especially leprosy.

PMID- 17222300
TI  - Photo-onycholysis due to indapamide.
AB  - Photo-onycholysis due to indapamide presented in a 75-year-old woman who was
      being treated with the diuretic for hypertension. The onset of her photo
      onycholysis was delayed because of inadvertent photoprotection in the form of
      artificial nails and occurred in the absence of a generalized photosensitive
      eruption. Her nails returned to normal after withdrawal of the drug and
      application of opaque nail polish.

PMID- 17222301
TI  - Unilateral limited scleroderma-like changes following formation of an
      arteriovenous fistula.
AB  - A 55-year-old man presented with a 1-year history of progressive skin thickening
      involving the right hand associated with Raynaud's phenomenon, sclerodactyly and
      painful cutaneous ulcers. An arteriovenous fistula for haemodialysis had been
      formed on the same arm 2 years previously. There were no symptoms or signs of
      systemic sclerosis or involvement of the contralateral arm. The limb was
      clinically ischaemic, attributed to a vascular steal phenomenon from the
      arteriovenous fistula, superimposed on occlusive arterial disease. A
      revascularization procedure was performed, which resulted in substantial
      improvement in the sclerodactyly, Raynaud's phenomenon and hand function. Tissue
      hypoxia is believed to be a contributing factor in the pathogenesis of
      scleroderma, and this case demonstrates scleroderma-like changes in the setting
      of limb ischaemia.

PMID- 17222302
TI  - Fabry disease in a heterozygote presenting as hand ischaemia and painful
      acroparaesthesia.
AB  - A 48-year-old woman presented with acute unilateral ischaemia of the left hand.
      She had a background of chronic peripheral neuropathic pain, palpitations,
      anaemia and an episode of superficial thrombophlebitis. Physical examination
      revealed non-blanching purple discoloration of her left fingers and her left
      thumb, index finger and thenar eminance appeared ischaemic. Digital subtraction
      angiography of the left hand demonstrated reduced flow. Skin punch biopsy
      histology was unremarkable. The diagnosis of Fabry disease was made on urine
      lipid profile analysis and confirmed by reduced peripheral blood leukocyte alpha
      galactosidase A activity.

PMID- 17222303
TI  - Treatment of female pattern hair loss with a combination of spironolactone and
      minoxidil.
AB  - A 53-year-old woman with clinical evidence of female pattern hair loss and
      histological evidence of androgenetic alopecia was initially treated with the
      oral antiandrogen spironolactone 200 mg daily. Serial scalp photography
      documented hair regrowth at 12 months; however, the hair regrowth plateaued, and
      at 24 months there had been no further improvement in hair density. Twice daily
      therapy with topical minoxidil 5% solution was then introduced and further
      regrowth documented, confirming the additive effect of combination therapy.

PMID- 17222304
TI  - A 30-year history of CD4+ vesiculo-bullous mycosis fungoides and multiple
      visceral malignancies.
AB  - An 83-year-old Caucasian woman presented with a 25-year history of an itchy,
      eczematous blistering eruption affecting her trunk and acral sites. She had a
      past history of adenocarcinoma of the lung, colorectal carcinoma and bladder
      carcinoma. Several skin biopsies consistently showed features of a spongiotic
      process. Direct and indirect immunofluorescence studies were repeatedly negative,
      excluding the possibility of an autoimmune blistering disorder. A skin biopsy
      several years later, however, showed histological and immunophenotypic features
      of mycosis fungoides. The literature on this rare phenotype of cutaneous T-cell
      lymphoma generally portrays a negative prognosis. Our case illustrates an
      excellent prognosis with stable disease 30 years after onset.

PMID- 17222305
TI  - Facial Sweet's syndrome mimicking rosacea fulminans.
AB  - A 36-year-old man presented with a non-pruritic, erythematous facial rash with
      peri-oral and peri-orbital sparing. The initial clinicopathological diagnosis was
      rosacea fulminans, which was treated with 25 mg oral prednisolone and cephalexin.
      The patient re-presented 1 week later with exacerbation of his rash in addition
      to constitutional symptoms of fever and malaise. A further skin biopsy was taken
      and the marked neutrophilic infiltrate in the absence of vasculitis made the
      diagnosis of Sweet's syndrome (acute febrile neutrophilic dermatosis). High-dose
      prednisolone (50 mg daily), topical hydrocortisone cream and ichthammol in zinc
      ointment were commenced with rapid clinical improvement. This case highlights the
      importance of considering Sweet's syndrome as a differential diagnosis when
      presented with a facial eruption.

PMID- 17222306
TI  - Pure cutaneous Langerhans cell histiocytosis resembling varicella.
AB  - A 5-month-old boy presented with multiple, pinkish-yellow, umblicated,
      varicelliform vesicles on his trunk. The lesions first appeared on his scalp 2
      months earlier. There was also an erythematous, moist and erosive eruption on
      both axillae, inguinal regions and intergluteal sulcus. He had been treated with
      topical antibacterial and antiviral therapies. Histopathological investigation of
      the lesions revealed the diagnosis of Langerhans cell histiocytosis. Systemic
      involvement was not detected, although detailed investigation was performed. We
      present our case because he had a varicelliform and intertriginous eruption but
      did not have internal organ and haematological involvement.

PMID- 17222307
TI  - Circumscribed palmar hypokeratosis.
AB  - A 66-year-old woman presented with a 40-year history of a slowly enlarging
      erythematous patch on the left thenar eminence. Histopathology showed a sharp
      'step' between the uninvolved and involved skin. Epidermal dysplasia and a
      cornoid lamella were not seen. These are the typical features of circumscribed
      palmar hypokeratosis.

PMID- 17222308
TI  - Digital nerve blocks: More gain with less pain.
AB  - Digital nerve blocks are commonly used and effective techniques for achieving
      anaesthesia of the digit for the purposes of enabling a variety of surgical
      procedures to be performed. Several techniques have been described including the
      traditional method, the metacarpal block and the transthecal approach. We favour
      the traditional technique, and describe a variation of the technique.

PMID- 17222309
TI  - Contact dermatitis to a canine anti-dandruff shampoo.
AB  - A 40-year-old teacher presented after her third episode of acute facial oedema
      within 4 months. Each episode occurred 1-2 days after visiting her mother's
      house. Patch testing showed positive reactions to miconazole and econazole
      nitrate. The patient denied use of any antifungal creams, but it transpired that
      her mother's dog was being shampooed weekly with an antifungal shampoo containing
      miconazole. No further episodes were recorded after discontinuing the antifungal
      shampoo.

PMID- 17222314
TI  - Risk factors for colorectal neoplasia in inflammatory bowel disease: a nested
      case-control study from Copenhagen county, Denmark and Olmsted county, Minnesota.
AB  - OBJECTIVES: Population-based data on risk factors and protective factors for
      colorectal dysplasia and cancer in patients with inflammatory bowel disease (IBD)
      are sparse. We conducted a nested case-control study of such factors in two well
      described IBD cohorts from Copenhagen County, Denmark and Olmsted County,
      Minnesota. METHODS: Forty-three neoplasia cases were matched on six criteria to 1
      3 controls (N = 102). Medical records were scrutinized for demographic and
      clinical data. For each variable, the odds of neoplasia were estimated using
      conditional logistic regression. RESULTS: Primary sclerosing cholangitis (PSC)
      (odds ratio [OR] 6.9, 95% confidence interval [CI] 1.2-40), percentage of disease
      course with clinically active disease (OR [per 5% increase] 1.2, 95% CI 0.996
      1.4), and >or=1 yr of continuous symptoms (OR 3.2, 95% CI 1.2-8.6) were
      associated with neoplasia, whereas a borderline association with median number of
      small-bowel x-rays (OR 1.3, 95% CI 0.96-1.6) was observed. We did not observe a
      protective effect of frequency of physician visits (OR 1.4, 95% CI 0.96-2.0),
      number of colonoscopies (OR 1.4, 95% CI 1.0-2.1), cumulative dose of
      sulfasalazine (OR [per 1,000 g] 1.1, 95% CI 1.0-1.3) and mesalamine (OR [per
      1,000 g] 1.3, 95% CI 0.9-1.9), or partial intestinal resections (OR 1.5, 95% CI
      0.3-7.1). CONCLUSIONS: Subgroups of IBD patients-those with PSC, severe long
      standing disease, and exposure to x-ray-were at greater risk of colorectal
      neoplasia. The protective effect of close follow-up, colonoscopy, and treatment
      with 5-aminosalicylates was questionable.

PMID- 17222315
TI  - Endoscopic interventions in the small bowel using double balloon enteroscopy:
      feasibility and limitations.
AB  - BACKGROUND: Double-balloon enteroscopy (DBE) is a new endoscopic tool that not
      only allows diagnostic workup of small bowel diseases, but also makes it possible
      to carry out therapeutic interventions. However, for a variety of reasons,
      endoscopic therapy appears to be more difficult to carry out deep in the small
      bowel than in the upper or lower gastrointestinal tract. AIM: The purpose of this
      study was to evaluate the acute technical success and acute complication rate of
      DBE. PATIENTS: Between June 2003 and July 2006, 353 patients (152 women, 201 men;
      mean age 60.3 +/- 17.1 yr) with suspected or known small bowel disease underwent
      635 consecutive DBE procedures. The majority of the patients were suffering from
      midgastrointestinal bleeding (N = 210, 60%). The overall diagnostic yield was 75%
      (265/353) for relevant lesions in the small bowel. The overall therapeutic yield
      was 67% (236/353). METHODS: Endoscopic therapy was performed in 59% of these
      patients (139/236). All therapeutic interventions were done in an inpatient
      manner. The majority of the procedures were carried out with the patients under
      conscious sedation (N = 130, 73%); sedation with propofol was administered in 37
      (20.8%) and with a combination of propofol and meperidine in 11 (6.2%)
      investigations. RESULTS: A total of 178 therapeutic procedures was carried out. A
      median of 270 cm of the small bowel was visualized using the oral route and a
      median of 150 cm using the anal route. The investigation time averaged 78 +/- 30
      minutes. The endoscopic treatments included argon plasma coagulation (APC, 102
      treatment sessions), injection therapy (N = 2), a combination of APC and
      injection (N = 6), polypectomies (N = 46), dilation therapy (N = 18), and foreign
      body extraction (N = 3). In 6/178 cases (3.4%), polypectomy (N = 2), dilation (N
      = 3), and implantation of a self-expanding metal stent (N = 1) could not be
      performed successfully for technical or anatomical reasons. Severe treatment
      associated complications occurred in six of the 178 therapeutic procedures (3.4%)
      and 4/139 patients (2.9%), consisting of bleeding (N = 2) and perforation (N = 3)
      during and after polypectomy of large polyps (>3 cm in size), as well as one case
      of segmental enteritis after APC. CONCLUSIONS: Endoscopic therapeutic
      interventions can be performed safely even in the more difficult conditions of
      the small bowel in the majority of patients. Polypectomy of large polyps appears
      to be the procedure associated with the highest risk.

PMID- 17222316
TI  - Long-term outcome of Crohn's disease following corticosteroid-induced remission.
AB  - INTRODUCTION: Corticosteroids are the gold standard in the treatment of moderate
      to severe Crohn's disease but are often associated with severe and potentially
      dangerous side effects. Despite an initial clinical response many patients become
      steroid dependent or require further steroid courses in the long term. The aim of
      the present study was to assess the probability of the need for further steroid
      treatment in Crohn's disease patients following steroid-induced remission and to
      establish if clinical variables can predict further steroid needs. PATIENTS AND
      All METHODS: patients at their first steroid course and with corticosteroid
      induced remission, defined as a Crohn's Disease Activity Index (CDAI) <150, 4 wk
      after steroid weaning, were studied and observed at follow-up for 12 months. The
      main outcome was clinical relapse requiring further steroid treatment.
      Statistical analysis was performed using the Kaplan-Meier method and
      multivariable Cox proportional hazard regression model taking into consideration
      gender, age at diagnosis, disease location and behavior, smoking habits, CDAI
      score before steroid treatment, and C reactive protein values at steroid weaning,
      as covariates. RESULTS: A total of 77 patients with steroid-induced remission
      were included. One-year follow-up was available in 75 of the 77 patients (97.4%).
      During follow-up 49 of 75 patients (65.3%) maintained remission or presented mild
      relapse not requiring steroids while 26 of 75 patients (34.6%) had moderate to
      severe relapse requiring further steroid treatment. The cumulative probability of
      a course free from steroids was 93.3%, 82.6%, 78.6%, and 66.6% at 3, 6, 9, and 12
      months, respectively. At multivariate analysis, increased C reactive protein at
      steroid weaning and penetrating complications were independent risk factors for
      further steroid requirement (OR 5.57, 95% CI 1.20-25.91, P= 0.001 and OR 4.20,
      95% CI 1.76-10.04, P= 0.005, respectively). CONCLUSION: Despite an initial
      clinical response and successful steroid tapering, 35% of patients required
      further steroid treatment within 1 yr. An increased C reactive protein value, at
      steroid weaning, despite clinical remission, and penetrating complications may
      predict further steroid requirement in already steroid responsive patients.

PMID- 17222317
TI  - Endoscopist can be more powerful than age and male gender in predicting adenoma
      detection at colonoscopy.
AB  - BACKGROUND AND AIMS: Both advancing age and male gender are known predictors of
      adenomas and large adenomas at colonoscopy. However, the importance of
      endoscopist compared with both age and gender as predictors of adenomas is not
      known. In this study, we assessed the adenoma detection rates of nine
      endoscopists performing colonoscopy and the effects of endoscopist on adenoma
      detection compared with the established predictors of advancing age and male
      gender. METHODS: Consecutive colonoscopy reports by nine attending
      gastroenterologists at Indiana University Hospital between January 1999 and
      January 2004 were obtained. Patients with indications for inflammatory bowel
      disease (IBD), inherited colon cancer syndromes, or who were referred for
      polypectomy were excluded. RESULTS: There were 10,034 included colonoscopies. The
      overall mean age (yr) +/- SD for the entire cohort was 56.0 +/- 13.5, range 14-93
      yr. Multivariate analysis indicated that both advancing age and male gender were
      powerful predictors of adenomas, both for the overall cohort and in those >or=50
      of age (P<or= 0.0001). The prevalence of adenomas increased from 14.6% at age 30
      to 35.2% at age 70. Men had more adenomas than women (24.4%vs 16.6%, P<or=
      0.0001). Among patients >or=50 yr of age, the range of detection of at least one
      adenoma per colonoscopy by nine colonoscopists was 15.5-41.1%, at least two
      adenomas was 4.9-20.0%, at least three adenomas was 0.8-10.8%, and at least one
      adenoma >or=1.0 cm was 1.7-6.2%, and the range of adenomas detected per
      colonoscopy was 0.21-0.86. Differences between endoscopists were significant (P <
      0.001). CONCLUSION: Who performs the procedure can be more important than age and
      gender in predicting adenomas at colonoscopy. Our results underscore the need to
      measure adenoma detection rates in the continuous quality improvement process and
      to report them to endoscopists. Additional data are needed to determine whether
      corrective measures can reduce variation in adenoma detection rates.

PMID- 17222318
TI  - EGD in children with abdominal pain: a systematic review.
AB  - BACKGROUND: We performed a systematic review to examine the diagnostic yield
      (endoscopic and histologic) of esophagogastroduodenoscopy (EGD) for the
      evaluation of abdominal pain of unclear etiology in children. We also examined
      the effect of EGD on change in treatment, quality of life, change in abdominal
      pain, and cost-effectiveness. METHODS: All full-length articles published in
      English during 1966-2005 were included if: (a) participants had abdominal pain
      without known underlying gastrointestinal disease, (b) participants underwent EGD
      primarily for the evaluation of abdominal pain, (c) findings of the EGD were
      reported, (d) participants were under 18 yr, and (e) sample size greater than 50.
      RESULTS: Eighteen articles examining 1,871 patients fulfilled the inclusion and
      exclusion criteria. All were observational and most (13) were prospective. Only
      three studies were performed in the United States and of those two were
      prospective. The largest study examined about 400 procedures and 13 studies
      examined less than 100 procedures. One case of inflammatory bowel disease and 67
      duodenal or gastric ulcers were reported, thus diagnostic yield was achieved in
      3.6% of cases. The prevalence of nonspecific histological gastrointestinal
      inflammatory lesions varied between 23% and 93%. Six articles attempted to
      correlate endoscopic or histologic findings with treatment management decisions.
      No articles attempted to describe quality of life or cost-effectiveness. None of
      the studies analyzed the association of alarm symptoms or signs to diagnostic
      yield. CONCLUSIONS: The diagnostic yield of EGD in children with unclear
      abdominal pain is low; however, existing studies are inadequate. The effect of
      EGD on change in treatment, quality of life, improvement of abdominal pain, and
      cost-effectiveness is unknown. The predictors of significant findings are
      unclear. Our findings suggest that a large multicenter study examining clinical
      factors, biopsy reports, and addressing patient outcomes is needed to further
      clarify the value of EGD in children with abdominal pain.

PMID- 17222319
TI  - Inhibitory control test is a simple method to diagnose minimal hepatic
      encephalopathy and predict development of overt hepatic encephalopathy.
AB  - OBJECTIVES: To compare inhibitory control test (ICT), a simple/rapid test of
      attention, to a standard psychometric battery (SPT) to diagnose minimal hepatic
      encephalopathy (MHE) and predict development of overt hepatic encephalopathy
      (OHE) in cirrhotic patients. METHODS: Fifty nonalcoholic cirrhotics and 50
      age/educational-status-matched controls were given ICT and SPT in the same
      sitting. Performance impaired beyond two standard deviations of controls was
      considered MHE in cirrhotics. ICT results (lure/target response and lures/person)
      were compared between controls and cirrhotics and within cirrhotics with/without
      MHE. Receiver-operating characteristic analysis was used to study ICT for MHE
      diagnosis. Twenty subjects were administered SPT and ICT twice to assess test
      retest reliability. All cirrhotics were followed routinely for the development of
      OHE. RESULTS: Cirrhotics performed worse than controls on SPT and ICT. Using SPT,
      39 cirrhotics had MHE. ICT was administered faster than SPT (15 vs 37 min).
      Cirrhotics with MHE had significantly higher lure (28%vs 3%) and lower target
      response (91%vs 96%) compared with those without MHE. Lure/person >5 had 90%
      sensitivity/specificity for MHE diagnosis. AUC for receiver-operating
      characteristic for lures alone was 95.8%. Lure and target responses were highly
      correlated (r= 0.9) between sessions showing high test-retest reliability. Five
      (10%) patients developed OHE on f/u of 26 +/- 10 months; all five had been
      diagnosed with MHE using ICT and SPT. None of the five patients with discordant
      results on SPT and ICT developed OHE. CONCLUSIONS: ICT has good
      sensitivity/specificity for MHE diagnosis, is reliable and is equivalent to SPT
      for predicting OHE development.

PMID- 17222320
TI  - Low-dose naltrexone therapy improves active Crohn's disease.
AB  - OBJECTIVES: Endogenous opioids and opioid antagonists have been shown to play a
      role in healing and repair of tissues. In an open-labeled pilot prospective
      trial, the safety and efficacy of low-dose naltrexone (LDN), an opioid
      antagonist, were tested in patients with active Crohn's disease. METHODS:
      Eligible subjects with histologically and endoscopically confirmed active Crohn's
      disease activity index (CDAI) score of 220-450 were enrolled in a study using 4.5
      mg naltrexone/day. Infliximab was not allowed for a minimum of 8 wk prior to
      study initiation. Other therapy for Crohn's disease that was at a stable dose for
      4 wk prior to enrollment was continued at the same doses. Patients completed the
      inflammatory bowel disease questionnaire (IBDQ) and the short-form (SF-36)
      quality of life surveys and CDAI scores were assessed pretreatment, every 4 wk on
      therapy and 4 wk after completion of the study drug. Drug was administered by
      mouth each evening for a 12-wk period. RESULTS: Seventeen patients with a mean
      CDAI score of 356 +/- 27 were enrolled. CDAI scores decreased significantly (P=
      0.01) with LDN, and remained lower than baseline 4 wk after completing therapy.
      Eighty-nine percent of patients exhibited a response to therapy and 67% achieved
      a remission (P < 0.001). Improvement was recorded in both quality of life surveys
      with LDN compared with baseline. No laboratory abnormalities were noted. The most
      common side effect was sleep disturbances, occurring in seven patients.
      CONCLUSIONS: LDN therapy appears effective and safe in subjects with active
      Crohn's disease. Further studies are needed to explore the use of this compound.

PMID- 17222321
TI  - Clearance of HCV improves insulin resistance, beta-cell function, and hepatic
      expression of insulin receptor substrate 1 and 2.
AB  - OBJECTIVES: Hepatitis C virus (HCV) infection is linked to greater insulin
      resistance. Although HCV itself is a candidate for the development of insulin
      resistance, the effects of antiviral treatment on impaired glucose metabolism
      remain unclear. The aim of this study is to examine the effects of clearance of
      HCV on insulin resistance, beta-cell function, and hepatic expression of insulin
      receptor substrate (IRS)1/2, central molecules for insulin signaling. METHODS: We
      analyzed 89 biopsy-proven patients with chronic HCV infection. Patients received
      interferon-alpha or interferon-alpha plus ribavirin for 6 months and were
      classified into three groups at 6 months after the conclusion of antiviral
      therapy according to their response to antiviral therapy: sustained responders (N
      = 29), relapsers (N = 12), and nonresponders (N = 48). Insulin resistance and
      beta-cell function were assessed by the homeostasis model assessment method (HOMA
      IR and HOMA-%B, respectively). Hepatic expression of IRS1/2 was evaluated by
      immunoblotting and immunostaining in 14 sustained responders. RESULTS: In
      nonresponders and relapsers, there were no significant changes in HOMA-IR and
      HOMA-%B values after antiviral therapy. On the other hand, in sustained
      responders, HOMA-IR values significantly decreased to 1.7 +/- 0.8 from 3.1 +/-
      1.1 (P < 0.05) after antiviral therapy. Similarly, HOMA-%B values significantly
      decreased to 90.6 +/- 10.0 from 113.7 +/- 15.3 (P < 0.05). Immunoblotting showed
      a threefold increase in IRS1/2 expression after clearance of HCV. Immunostaining
      revealed that greater IRS1/2 expression was seen in hepatocytes. CONCLUSIONS: We
      showed that clearance of HCV improves insulin resistance, beta-cell function, and
      hepatic IRS1/2 expression.

PMID- 17222322
TI  - An inverse relationship between markers of fibrogenesis and collagen degradation
      in patients with or without alcoholic liver disease.
AB  - OBJECTIVES: Excessive deposition of collagen leading to cirrhosis is a major
      complication of alcohol abuse. However, the mechanisms behind the accumulation of
      the extracellular matrix proteins are poorly understood. METHODS: We measured
      serum markers of collagen degradation (beta-CTx), fibrogenesis (PINP, PIIINP),
      and pro- and anti-inflammatory cytokines from 84 male heavy drinkers, who were
      either with (N = 52) or without (N = 32) clinical or histological signs of
      alcoholic liver disease (ALD), and from 20 healthy nonalcoholic controls.
      RESULTS: Serum beta-CTx levels in ALD patients were significantly lower than in
      healthy controls or in the alcoholics without liver disease, while PINP and
      PIIINP, reflecting type I and type III collagen synthesis, respectively, were
      significantly increased. The alcoholics without liver disease showed values, that
      were not significantly different from those of healthy controls. Serum beta-CTx
      correlated negatively with serum PIIINP and proinflammatory cytokines (IL-2, IL
      6, IL-8, TNF-alpha), and positively with anti-inflammatory cytokines (IL-1, TGF
      beta), whereas serum PIIINP correlated positively with these proinflammatory
      cytokines and negatively with the anti-inflammatory cytokines. Calculation of
      PIIINP/beta-CTx ratio was found to yield an excellent sensitivity (94%) and
      specificity (98%) in differentiating the alcoholics with liver disease.
      CONCLUSION: The present findings indicate a positive relationship between markers
      of collagen biosynthesis and proinflammatory cytokines, and a negative
      relationship between these markers and a marker of collagen degradation and anti
      inflammatory cytokines, suggesting that a disturbed balance in these cellular
      responses may facilitate fibrogenesis and play a pivotal role in the pathogenesis
      of ALD. These findings should also be implicated in the development of
      noninvasive tools for discriminating individuals at risk for fibrogenesis.

PMID- 17222323
TI  - Spectrum of liver histology in presumed decompensated alcoholic liver disease.
AB  - BACKGROUND: In presumed decompensated alcoholic liver disease (ALD; liver
      decompensation, heavy alcohol intake, and negative results of noninvasive
      screening for other causes), liver biopsy is often performed to assess severity
      of liver injury and to rule out other liver diseases. AIM: The aim of the study
      is to describe the spectrum of liver histology in such patients. METHODS: We
      reviewed all patients with presumed decompensated ALD seen between 1998 and 2004,
      in whom liver tissue was available for histology (N = 110). RESULTS: A total of
      104 of the 110 patients had at least one of the histological features suggestive
      of ALD: fat, Mallory's hyalin, neutrophilic infiltrate, and hepatocyte
      ballooning. These features were more prevalent in tissue obtained within a month
      after presentation with decompensation than in that obtained before
      decompensation or more than 1 month after. These features were also associated
      with more severe liver dysfunction. Histology revealed a major additional
      diagnosis (Budd-Chiari syndrome) in only one case. In 41 patients biopsied within
      a month of first presentation with decompensation, Child score and Maddrey
      discriminant function (DF), but none of the histological features, were
      predictive of survival by Cox multivariate analysis. Of the 26 of these 41
      patients with a Maddrey DF >32, 22 (85%) had alcoholic hepatitis. CONCLUSIONS: In
      patients with presumed decompensated ALD, other liver diseases are uncommon.
      Routine liver biopsy is of limited added value but biopsy should be considered in
      those in whom the noninvasive workup, or failure to recover despite abstinence,
      raises the possibility of other liver diseases.

PMID- 17222324
TI  - Histamine H1 blocker hydroxyzine improves sleep in patients with cirrhosis and
      minimal hepatic encephalopathy: a randomized controlled pilot trial.
AB  - OBJECTIVES: Sleep difficulty is common in minimal hepatic encephalopathy (HE) and
      the mechanisms are not fully elucidated. Dysregulated histamine neurotransmission
      is associated with an altered circadian rhythmicity that is partially restored
      following central histamine H1 receptor blockade in cirrhotic animals. We studied
      the effects of the histamine H1 blocker hydroxyzine in sleep alterations in
      patients with cirrhosis in a double-blind, randomized controlled fashion.
      METHODS: A total of 35 patients (age 56 yr [36-69], Pugh's score 9 [7-12],
      portosystemic shunt: N = 7) with minimal HE and long-standing sleep difficulties
      (8 months [4-48]) and free from benzodiazepines were randomized to hydroxyzine 25
      mg at bedtime (N = 17) or placebo (N = 18) for a 10-day period. Measurements of
      sleep behavior using visual analog scale and wrist actigraphy, neuropsychological
      tests, and protein s100beta serum levels were performed at baseline and at day
      10. RESULTS: Subjective improvement in sleep was observed in 40% of hydroxyzine
      treated patients but in none receiving placebo (P < 0.04). Objectively, 65% of
      hydroxyzine-treated patients versus 25% of patients under placebo had a >or=30%
      increase in sleep efficiency as measured by wrist actigraphy (P < 0.04).
      Neuropsychological tests (Z scores) and protein s100beta levels remained
      statistically unchanged in both groups. One patient developed an acute episode of
      encephalopathy reversible upon cessation of hydroxyzine. CONCLUSIONS: In contrast
      to placebo, hydroxyzine 25 mg at bedtime improved sleep behavior (subjectively
      and using wrist actigraphy) in patients with cirrhosis and minimal HE. The risk
      of precipitating overt HE warrants some caution when prescribing this drug.

PMID- 17222326
TI  - Hepatic steatosis in genotype 4 chronic hepatitis C is mainly because of
      metabolic factors.
AB  - BACKGROUND/AIM: Hepatic steatosis is considered to be mostly associated with
      viral factors in genotype 3 and metabolic factors in genotype 1 chronic hepatitis
      C, while there are rather few data for genotype 4. We determined the parameters
      associated with steatosis in 350 chronic hepatitis C patients, focusing on
      genotype 4. METHODS: Histological lesions were evaluated according to Ishak's
      classification and steatosis was semiquantitatively graded. Several patient
      characteristics on the biopsy day were also evaluated. RESULTS: Steatosis was
      present in 73% of patients without significant differences among genotypes.
      Moderate/severe steatosis was more frequent in genotype 3 than 4 (44% vs 26%, P=
      0.025) and similar between genotype 4 and 1 patients. Moderate/severe steatosis
      was associated with body mass index (BMI) in genotype 4 (P= 0.023) and gamma
      glutamyl-transpeptidase in genotype 3 patients (P= 0.044). In 150 nondiabetic
      patients with BMI < or =25 kg/m(2), moderate/severe steatosis was present in 15,
      40, and 11% of genotype 1, 3, and 4 patients, respectively, (P= 0.005) and was
      independently associated only with genotype 3. In multivariate analysis,
      steatosis grade or moderate/severe steatosis was independently associated with
      higher BMI, genotype 3, and lower cholesterol. CONCLUSIONS: Moderate or severe
      steatosis is significantly less frequent in genotype 4 than 3 chronic hepatitis C
      patients and similar between genotype 4 and 1. In nondiabetic, nonoverweight
      patients, moderate or severe steatosis is present in only 10-15% of genotype 4 or
      1 compared with 40% of genotype 3 patients. Thus, hepatic steatosis in genotype 4
      is mostly associated with metabolic factors, similar to those in genotype 1.

PMID- 17222325
TI  - Endoscopic treatment for suprapancreatic biliary stricture following blunt
      abdominal trauma.
AB  - OBJECTIVES: Suprapancreatic biliary stricture associated with blunt abdominal
      trauma is extremely rare. Therefore, no definitive treatment modality for this
      stricture has been fully established. This study was designed to evaluate the
      efficacy and long-term follow-up of endoscopic treatment for suprapancreatic
      biliary stricture following blunt abdominal trauma. METHODS: Data from the
      institution's prospectively collected endoscopic retrograde
      cholangiopancreatography (ERCP) database, medical records, radiological findings,
      and trauma registry with operative records were used to identify patients with
      suprapancreatic biliary stricture associated with blunt abdominal trauma.
      RESULTS: Eight patients (six men and two women) with a median age of 36 yr
      (interquartile range [IQR] 29-53 yr) were included in this study. The median
      interval between the initial trauma and the onset of symptoms was 23 days (IQR 16
      51 days). The median length of biliary stricture was 1 cm (IQR 0.6-1 cm).
      Endoscopic plastic stent placement was successfully performed in all patients
      included in the study. The median duration of stent placement was 2 months (IQR 2
      2.8 months). Follow-up ERCP showed improved or resolved biliary stricture in all
      patients. There was no recurrence of symptoms after the removal of the stents;
      therefore, surgery was unnecessary in these patients. Long-term follow-up (median
      33 months) was also excellent. CONCLUSIONS: Endoscopic plastic stent placement
      may be a good candidate for first-line management for suprapancreatic biliary
      strictures following blunt abdominal trauma. Furthermore, the long-term results
      for this type of biliary stricture with endoscopic stent placement may be
      excellent.

PMID- 17222327
TI  - The vertebrate phylotypic stage and an early bilaterian-related stage in mouse
      embryogenesis defined by genomic information.
AB  - BACKGROUND: Embryos of taxonomically different vertebrates are thought to pass
      through a stage in which they resemble one another morphologically. This
      "vertebrate phylotypic stage" may represent the basic vertebrate body plan that
      was established in the common ancestor of vertebrates. However, much controversy
      remains about when the phylotypic stage appears, and whether it even exists. To
      overcome the limitations of studies based on morphological comparison, we
      explored a comprehensive quantitative method for defining the constrained stage
      using expressed sequence tag (EST) data, gene ontologies (GO), and available
      genomes of various animals. If strong developmental constraints occur during the
      phylotypic stage of vertebrate embryos, then genes conserved among vertebrates
      would be highly expressed at this stage. RESULTS: We established a novel method
      for evaluating the ancestral nature of mouse embryonic stages that does not
      depend on comparative morphology. The numerical "ancestor index" revealed that
      the mouse indeed has a highly conserved embryonic period at embryonic day 8.0
      8.5, the time of appearance of the pharyngeal arch and somites. During this
      period, the mouse prominently expresses GO-determined developmental genes shared
      among vertebrates. Similar analyses revealed the existence of a bilaterian
      related period, during which GO-determined developmental genes shared among
      bilaterians are markedly expressed at the cleavage-to-gastrulation period. The
      genes associated with the phylotypic stage identified by our method are essential
      in embryogenesis. CONCLUSION: Our results demonstrate that the mid-embryonic
      stage of the mouse is indeed highly constrained, supporting the existence of the
      phylotypic stage. Furthermore, this candidate stage is preceded by a putative
      bilaterian ancestor-related period. These results not only support the
      developmental hourglass model, but also highlight the hierarchical aspect of
      embryogenesis proposed by von Baer. Identification of conserved stages and
      tissues by this method in various animals would be a powerful tool to examine the
      phylotypic stage hypothesis, and to understand which kinds of developmental
      events and gene sets are evolutionarily constrained and how they limit the
      possible variations of animal basic body plans.

PMID- 17222329
TI  - Comprehensive genetic and epigenetic analysis of sporadic meningioma for macro
      mutations on 22q and micro-mutations within the NF2 locus.
AB  - BACKGROUND: Meningiomas are the most common intracranial neoplasias, representing
      a clinically and histopathologically heterogeneous group of tumors. The
      neurofibromatosis type 2 (NF2) tumor suppressor is the only gene known to be
      frequently involved in early development of meningiomas. The objective of this
      study was to identify genetic and/or epigenetic factors contributing to the
      development of these tumors. A large set of sporadic meningiomas were analyzed
      for presence of 22q macro-mutations using array-CGH in order to identify tumors
      carrying gene dosage aberrations not encompassing NF2. The NF2 locus was also
      comprehensively studied for point mutations within coding and conserved non
      coding sequences. Furthermore, CpG methylation within the NF2 promoter region was
      thoroughly analyzed. RESULTS: Monosomy 22 was the predominant finding, detected
      in 47% of meningiomas. Thirteen percent of the tumors contained
      interstitial/terminal deletions and gains, present singly or in combinations. We
      defined at least two minimal overlapping regions outside the NF2 locus that are
      small enough (approximately 550 kb and approximately 250 kb) to allow analysis of
      a limited number of candidate genes. Bialleinactivationo the NF2 gne was detected
      in 36% of meningiomas. Among the monosomy 22 cases, no additional NF2 mutations
      could be identified in 35% (17 out of 49) of tumors. Furthermore, the majority of
      tumors (9 out of 12) with interstitial/terminal deletions did not have any
      detectable NF2 mutations. Methylation within the NF2 promoter region was only
      identified at a single CpG site in one tumor sample. CONCLUSION: We confirmed
      previous findings of pronounced differences in mutation frequency between
      different histopathological subtypes. There is a higher frequency of biallelic
      NF2 inactivation in fibroblastic (52%) compared to meningothelial (18%) tumors.
      The presence of macro-mutations on 22q also shows marked differences between
      fibroblastic (86%) and meningothelial (39%) subtypes. Thus, inactivation of NF2,
      often combined with the presence of macro-mutation on 22q, is likely not as
      important for the development of the meningothelial subtype, as opposed to the
      fibroblastic form. Analysis of 40 CpG sites distributed within 750 bp of the
      promoter region suggests that NF2 promoter methylation does not play a major role
      in meningioma development.

PMID- 17222330
TI  - Bivariate random-effects meta-analysis and the estimation of between-study
      correlation.
AB  - BACKGROUND: When multiple endpoints are of interest in evidence synthesis, a
      multivariate meta-analysis can jointly synthesise those endpoints and utilise
      their correlation. A multivariate random-effects meta-analysis must incorporate
      and estimate the between-study correlation (rhoB). METHODS: In this paper we
      assess maximum likelihood estimation of a general normal model and a generalised
      model for bivariate random-effects meta-analysis (BRMA). We consider two applied
      examples, one involving a diagnostic marker and the other a surrogate outcome.
      These motivate a simulation study where estimation properties from BRMA are
      compared with those from two separate univariate random-effects meta-analyses
      (URMAs), the traditional approach. RESULTS: The normal BRMA model estimates rhoB
      as -1 in both applied examples. Analytically we show this is due to the maximum
      likelihood estimator sensibly truncating the between-study covariance matrix on
      the boundary of its parameter space. Our simulations reveal this commonly occurs
      when the number of studies is small or the within-study variation is relatively
      large; it also causes upwardly biased between-study variance estimates, which are
      inflated to compensate for the restriction on rhoB. Importantly, this does not
      induce any systematic bias in the pooled estimates and produces conservative
      standard errors and mean-square errors. Furthermore, the normal BRMA is
      preferable to two normal URMAs; the mean-square error and standard error of
      pooled estimates is generally smaller in the BRMA, especially given data missing
      at random. For meta-analysis of proportions we then show that a generalised BRMA
      model is better still. This correctly uses a binomial rather than normal
      distribution, and produces better estimates than the normal BRMA and also two
      generalised URMAs; however the model may sometimes not converge due to
      difficulties estimating rhoB. CONCLUSION: A BRMA model offers numerous advantages
      over separate univariate synthesises; this paper highlights some of these
      benefits in both a normal and generalised modelling framework, and examines the
      estimation of between-study correlation to aid practitioners.

PMID- 17222328
TI  - A procedure for the detection of linkage with high density SNP arrays in a large
      pedigree with colorectal cancer.
AB  - BACKGROUND: The apparent dominant model of colorectal cancer (CRC) inheritance in
      several large families, without mutations in known CRC susceptibility genes,
      suggests the presence of so far unidentified genes with strong or moderate effect
      on the development of CRC. Linkage analysis could lead to identification of
      susceptibility genes in such families. In comparison to classical linkage
      analysis with multi-allelic markers, single nucleotide polymorphism (SNP) arrays
      have increased information content and can be processed with higher throughput.
      Therefore, SNP arrays can be excellent tools for linkage analysis. However, the
      vast number of SNPs on the SNP arrays, combined with large informative pedigrees
      (e.g. >35-40 bits), presents us with a computational complexity that is
      challenging for existing statistical packages or even exceeds their capacity. We
      therefore setup a procedure for linkage analysis in large pedigrees and validated
      the method by genotyping using SNP arrays of a colorectal cancer family with a
      known MLH1 germ line mutation. METHODS: Quality control of the genotype data was
      performed in Alohomora, Mega2 and SimWalk2, with removal of uninformative SNPs,
      Mendelian inconsistencies and Mendelian consistent errors, respectively. Linkage
      disequilibrium was measured by SNPLINK and Merlin. Parametric linkage analysis
      using two flanking markers was performed using MENDEL. For multipoint parametric
      linkage analysis and haplotype analysis, SimWalk2 was used. RESULTS: On
      chromosome 3, in the MLH1-region, a LOD score of 1.9 was found by parametric
      linkage analysis using two flanking markers. On chromosome 11 a small region with
      LOD 1.1 was also detected. Upon linkage disequilibrium removal, multipoint
      linkage analysis yielded a LOD score of 2.1 in the MLH1 region, whereas the LOD
      score dropped to negative values in the region on chromosome 11. Subsequent
      haplotype analysis in the MLH1 region perfectly matched the mutation status of
      the family members. CONCLUSION: We developed a workflow for linkage analysis in
      large families using high-density SNP arrays and validated this workflow in a
      family with colorectal cancer. Linkage disequilibrium has to be removed when
      using SNP arrays, because it can falsely inflate the LOD score. Haplotype
      analysis is adequate and can predict the carrier status of the family members.

PMID- 17222331
TI  - Lymphatic vessels assessment in feline mammary tumours.
AB  - BACKGROUND: The lymphatic vessels play a crucial role in a variety of human
      cancers since tumour cell lymphatic invasion significantly influences prognosis.
      It is not known if pre-existing lymphatics are enough for tumour dissemination or
      de novo development is necessary. VEGFR-3 is an angiogenetic mediator for both
      lymphatic and blood vessels during embryonic development, and only for lymphatics
      after birth. VEGF is a mediator of both vasculogenesis and angiogenesis,
      regulates the growth of lymphatics in various experimental models, and is
      produced in many solid tumours. CD44 mediates hyaluronic acid (HA)-dependent cell
      adhesion: besides promoting invasion, this interaction also supports
      neoangiogenesis that indirectly stimulates tumour cell proliferation. The
      expression of VEGF-C (Vascular Endothelial Growth Factor-C), its receptor VEGFR-3
      and CD44, were studied on feline mammary samples to assess the importance of
      lymphangiogenesis and lymphangiotrophism in neoplasia. METHODS: Samples were
      taken from six normal mammary glands (NMG), ten benign (BT) and 32 malignant (MT)
      tumours. Immunohistochemical laminin/VEGFR-3 double stain, VEGF-C and CD44 stains
      were applied to 4 mum-thick sections, and their expression evaluated in
      intratumoral/extratumoral and intramammary/extramammary fields. RESULTS: All
      groups revealed a higher number of lymphatics in the extratumoral/extramammary
      areas. VEGF-C expression in the epithelium paralleled the number of positive
      vessels in the NMG, BT and MT, whereas VEGF-C higher expression was noted in the
      intratumoral fields only in infiltrating MT. CD44 score was lower in extratumoral
      than intratumoral fields in tumours and showed a significant increase in
      extramammary/extratumoral fields from NMG to MT. Pearson test showed a
      significant and inversely proportional correlation between CD44 expression and
      the number of lymphatic vessels with VEGFR-3 in malignant infiltrating tumours.
      CONCLUSION: The number of both VEGFR-3 positive and negative lymphatics in the
      extratumoral and extramammary stroma was significantly higher than intratumoral
      and intramammary fields respectively in the NMG, BT and MT. This suggests a scant
      biological importance of intratumoral lymphatics while their higher number is due
      to the concentration of existing vessels following compression of the
      extratumoral stroma in spite of a non demonstrable increase from NMG to MT. The
      tumour model employed provided no evidence of lymphangiogenesis, and metastasis
      in the regional lymph node develops following the spread through the pre-existing
      lymphatic network.

PMID- 17222332
TI  - Use of tobacco and alcohol by Swiss primary care physicians: a cross-sectional
      survey.
AB  - BACKGROUND: Health behaviours among doctors has been suggested to be an important
      marker of how harmful lifestyle behaviours are perceived. In several countries,
      decrease in smoking among physicians was spectacular, indicating that the hazard
      was well known. Historical data have shown that because of their higher socio
      economical status physicians take up smoking earlier. When the dangers of smoking
      become better known, physicians began to give up smoking at a higher rate than
      the general population. For alcohol consumption, the situation is quite
      different: prevalence is still very high among physicians and the dangers are not
      so well perceived. To study the situation in Switzerland, data of a national
      survey were analysed to determine the prevalence of smoking and alcohol drinking
      among primary care physicians. METHODS: 2,756 randomly selected practitioners
      were surveyed to assess subjective mental and physical health and their
      determinants, including smoking and drinking behaviours. Physicians were
      categorised as never smokers, current smokers and former smokers, as well as non
      drinkers, drinkers (AUDIT-C < 4 for women and < 5 for men) and at risk drinkers
      (higher scores). RESULTS: 1'784 physicians (65%) responded (men 84%, mean age 51
      years). Twelve percent were current smokers and 22% former smokers. Sixty six
      percent were drinkers and 30% at risk drinkers. Only 4% were never smokers and
      non drinkers. Forty eight percent of current smokers were also at risk drinkers
      and 16% of at risk drinkers were also current smokers. Smoking and at risk
      drinking were more frequent among men, middle aged physicians and physicians
      living alone. When compared to a random sample of the Swiss population, primary
      care physicians were two to three times less likely to be active smokers (12% vs.
      30%), but were more likely to be drinkers (96% vs. 78%), and twice more likely to
      be at risk drinkers (30% vs. 15%). CONCLUSION: The prevalence of current smokers
      among Swiss primary care physicians was much lower than in the general population
      in Switzerland, reflecting that the hazards of smoking are well known to doctors.
      However, the opposite was found for alcohol use, underlining the importance of
      making efforts in this area to increase awareness among physicians of the dangers
      of alcohol consumption.

PMID- 17222333
TI  - A comparative study of the complications of surgical tracheostomy in morbidly
      obese critically ill patients.
AB  - INTRODUCTION: There is little objective comparative information about the
      postoperative complications of tracheostomy in morbidly obese patients. The aim
      of this study was to determine the incidence and severity of complications
      associated with open tracheostomy in critically ill morbidly obese patients
      during hospitalization. METHODS: During a six year period, all consecutive
      morbidly obese patients (body mass index [BMI] of greater than or equal to 40
      kg/m2) who underwent an elective open tracheostomy were compared to a control
      group (BMI of less than 40 kg/m2) of the same institution. Variables examined
      included age, gender, BMI, Charlson index, and reasons for tracheostomy. All
      postoperative tracheotomy-related complications that occurred during
      hospitalization, including death, were recorded. RESULTS: A tracheostomy was
      performed in 89 morbidly obese patients out of 427 critically ill patients. A
      total of 27 complications were recorded in 22 morbidly obese patients (25%)
      compared to 65 complications in 49 patients (14%) of the control group (p =
      0.03). The majority of these complications were minor in origin. Overall, nine
      serious events were responsible for two deaths in the morbidly obese compared to
      seven cases and two deaths in the control group (p = 0.001). Life-threatening
      complications were attributed to tube obstruction and malpositioning of the
      tracheostomy after being dislodged. In multivariate analysis, morbid obesity
      (odds ratio 4.4, 95% confidence interval 2.1 to 11.7) was independently
      associated with increased risk of tracheostomy-related complications. CONCLUSION:
      In the present series, morbid obesity is associated with increased frequency and
      life-threatening complications from conventional tracheostomy. Special techniques
      and operative policies must be applied to overcome loss of airway control.

PMID- 17222334
TI  - HEE-GER: a systematic review of German economic evaluations of health care
      published 1990-2004.
AB  - BACKGROUND: Studies published in non-English languages are systematically missing
      in systematic reviews of growth and quality of economic evaluations of health
      care. The aims of this study were: to characterize German evaluations, published
      in English or German-language, in terms of various key parameters; to investigate
      methods to derive quality-of-life weights in cost-utility studies; and to examine
      changes in study characteristics over the years. METHODS: We conducted a country
      specific systematic review of the German and English-language literature of
      German economic evaluations (assessment of or application to the German health
      care system) published 1990-2004. Generic and specialized health economic
      databases were searched. Two independent reviewers verified fulfillment of
      inclusion criteria and extracted study characteristics. RESULTS: The fulltexts of
      730 articles were reviewed of which 283 fulfilled all entry criteria. 32% of
      included studies were published in German-language. 51% of studies evaluated
      pharmaceuticals and 63% were cost-effectiveness analyses. Economic appraisals
      concentrate on few disease categories and important health areas are strongly
      underrepresented. Declaration of sponsorship was associated with article language
      (49% English articles vs. 29% German articles, p < 0.001). The methodology used
      to obtain quality-of-life weights in published cost-utility studies was very
      diverse, poorly reported and most studies did not use German patients' or
      community health state evaluations. CONCLUSION: Many of the German-language
      evaluations included in our study are likely to be missing in international
      reviews and may be systematically different from English-language reviews from
      Germany. Lack of transparency and adherence to recommended reporting practices
      constitute a serious problem in German economic evaluations.

PMID- 17222335
TI  - Collision of adenocarcinoma and gastrointestinal stromal tumour (GIST) in the
      stomach: report of a case.
AB  - A 78-year-old woman was diagnosed with a proximal gastric adenocarcinoma and
      underwent an elective D2 total gastrectomy with splenectomy. Subsequent
      histopathology revealed the presence of another tumour at the gastric antrum.
      This was a small benign gastrointestinal stromal tumour (GIST) mixed with gastric
      adenocarcinoma cells similar to those of the main gastric tumour i.e. a collision
      tumour. The literature has only few previous reports of this very rare
      association. It is not known whether this synchronicity is incidental or there is
      a causative factor inducing the development of tumours of different histotypes in
      the same organ. Pathologists, oncologists and surgeons should be aware of this
      interesting condition.

PMID- 17222337
TI  - Prostaglandin I2 enhances cough reflex sensitivity to capsaicin in the asthmatic
      airway.
AB  - Inflammatory mediators are involved in the pathogenesis of airway inflammation,
      but the role of prostaglandin I2 (PGI2) remains obscure. This study was designed
      to investigate the role of PGI2 in cough reflex sensitivity of the asthmatic
      airway, which is characterized by chronic eosinophilic airway inflammation. The
      effect of beraprost, a chemically and biologically stable analogue of PGI2, on
      cough response to inhaled capsaicin was examined in 21 patients with stable
      asthma in a randomized, placebo-controlled cross over study. Capsaicin cough
      threshold, defined as the lowest concentration of capsaicin eliciting five or
      more coughs, was measured as an index of airway cough reflex sensitivity. The
      cough threshold was significantly (p < 0.05) decreased after two weeks of
      treatment with beraprost [17.8 (GSEM 1.20) microM] compared with placebo [30.3
      (GSEM 1.21) microM]. PGI2 increases cough reflex sensitivity of the asthmatic
      airway, suggesting that inhibition of PGI2 may be a novel therapeutic option for
      patients with asthma, especially cough predominant asthma.

PMID- 17222336
TI  - Transcriptional profiling of the LPS induced NF-kappaB response in macrophages.
AB  - BACKGROUND: Exposure of macrophages to bacterial products such as
      lipopolysaccharide (LPS) results in activation of the NF-kappaB transcription
      factor, which orchestrates a gene expression programme that underpins the
      macrophage-dependent immune response. These changes include the induction or
      repression of a wide range of genes that regulate inflammation, cell
      proliferation, migration and cell survival. This process is tightly regulated and
      loss of control is associated with conditions such as septic shock, inflammatory
      diseases and cancer. To study this response, it is important to have in vitro
      model systems that reflect the behaviour of cells in vivo. In addition, it is
      necessary to understand the natural differences that can occur between
      individuals. In this report, we have investigated and compared the LPS response
      in macrophage derived cell lines and peripheral blood mononuclear cell (PBMC)
      derived macrophages. RESULTS: Gene expression profiles were determined following
      LPS treatment of THP-1 cells for 1 and 4 hours. LPS significantly induced or
      repressed 72 out of 465 genes selected as being known or putative NF-kappaB
      target genes, which exhibited 4 temporal patterns of expression. Results for 34
      of these genes, including several genes not previously identified as LPS target
      genes, were validated using real time PCR. A high correlation between microarray
      and real time PCR data was found. Significantly, the LPS induced expression
      profile of THP-1 cells, as determined using real time PCR, was found to be very
      similar to that of human PBMC derived macrophages. Interestingly, some
      differences were observed in the LPS response between the two donor PBMC
      macrophage populations. Surprisingly, we found that the LPS response in U937
      cells was dramatically different to both THP-1 and PBMC derived macrophages.
      CONCLUSION: This study revealed a dynamic and diverse transcriptional response to
      LPS in macrophages, involving both the induction and repression of gene
      expression in a time dependent manner. Moreover, we demonstrated that the LPS
      induced transcriptional response in the THP-1 cell line is very similar to
      primary PBMC derived macrophages. Therefore, THP-1 cells represent a good model
      system for studying the mechanisms of LPS and NF-kappaB dependent gene
      expression.

PMID- 17222338
TI  - Wnt/beta-catenin signaling is required for development of the exocrine pancreas.
AB  - BACKGROUND: Beta-catenin is an essential mediator of canonical Wnt signaling and
      a central component of the cadherin-catenin epithelial adhesion complex.
      Dysregulation of beta-catenin expression has been described in pancreatic
      neoplasia. Newly published studies have suggested that beta-catenin is critical
      for normal pancreatic development although these reports reached somewhat
      different conclusions. In addition, the molecular mechanisms by which loss of
      beta-catenin affects pancreas development are not well understood. The goals of
      this study then were; 1] to further investigate the role of beta-catenin in
      pancreatic development using a conditional knockout approach and 2] to identify
      possible mechanisms by which loss of beta-catenin disrupts pancreatic
      development. A Pdx1-cre mouse line was used to delete a floxed beta-catenin
      allele specifically in the developing pancreas, and embryonic pancreata were
      studied by immunohistochemistry and microarray analysis. RESULTS: Pdx1-cre floxed
      beta-catenin animals were viable but demonstrated small body size and shortened
      median survival. The pancreata from knockout mice were hypoplastic and
      histologically demonstrated a striking paucity of exocrine pancreas, acinar to
      duct metaplasia, but generally intact pancreatic islets containing all lineages
      of endocrine cells. In animals with extensive acinar hypoplasia, putative
      hepatocyte transdifferention was occasionally observed. Obvious and uniform
      pancreatic hypoplasia was observed by embryonic day E16.5. Transcriptional
      profiling of Pdx1-cre floxed beta-catenin embryonic pancreata at E14.5, before
      there was a morphological phenotype, revealed significant decreases in the beta
      catenin target gene N-myc, and the basic HLH transcription factor PTF1, and an
      increase of several pancreatic zymogens compared to control animals. By E16.5,
      there was a dramatic loss of exocrine markers and an increase in Hoxb4, which is
      normally expressed anterior to the pancreas. CONCLUSION: We conclude that beta
      catenin expression is required for development of the exocrine pancreas, but is
      not required for development of the endocrine compartment. In contrast, beta
      catenin/Wnt signaling appears to be critical for proliferation of PTF1+ nascent
      acinar cells and may also function, in part, to maintain an undifferentiated
      state in exocrine/acinar cell precursors. Finally, beta-catenin may be required
      to maintain positional identity of the pancreatic endoderm along the anterior
      posterior axis. This data is consistent with the findings of frequent beta
      catenin mutations in carcinomas of acinar cell lineage seen in humans.

PMID- 17222340
TI  - The association between timed up and go test and history of falls: the Tromso
      study.
AB  - BACKGROUND: Fall-related injuries in older adults are a major health problem.
      Although the aetiology of falls is multifactorial, physical factors are assumed
      to contribute significantly. The "Timed up and go test" (TUG) is designed to
      measure basic mobility function. This report evaluates the association between
      TUG times and history of falls. METHODS: A retrospective, observational,
      population-based study was conducted on 414 men and 560 women with mean age 77.5
      (SD 2.3). TUG time and falls during the previous 12 months were recorded.
      Covariates were age, sex, medical history and health-related mobility problems.
      Means, confidence intervals and test characteristics for TUG were calculated.
      Odds ratios and influence of covariates were examined by logistic regression.
      RESULTS: The mean TUG time was 11.1s (SD 2.5) among male non-fallers and 13.0s
      (SD 7.8) among fallers. The difference was 1.9s (95%CI 0.9-3.0). The odds ratio
      for fallers being in the upper quartile was 2.1 (95%CI 1.4-3.3). Adjusted for
      covariates, the odds ratio was (OR = 1.8, 95%CI 1.1-2.9). The corresponding mean
      was 13.0s (SD 5.74) among female non-fallers and 13.9s (SD 8.5) among fallers.
      The difference was 0.9 (95%CI -0.3-2.1). The odds ratio for fallers being in
      upper quartile was 1.0 (95%CI 0.7-1.4). The area under the ROC curve was 0.50
      (95%CI 0.45-0.55) in women and 0.56 (95%CI 0.50-0.62) in men. CONCLUSION: TUG is
      statistically associated with a history of falls in men but not in women. The
      ability to classify fallers is poor, and the clinical value of the association is
      therefore limited.

PMID- 17222339
TI  - Managing an effective treatment for neuroleptic malignant syndrome.
AB  - INTRODUCTION: Neuroleptic malignant syndrome (NMS) is a rare, but sometimes
      fatal, adverse reaction to neuroleptics characterized principally by fever and
      rigor. The aim of this study was to prove the efficacy of different NMS treatment
      strategies, focusing on the efficacy of dantrolene. METHODS: Altogether, 271 case
      reports were included. These cases were categorized into four treatment groups
      and compared to each other according to effectiveness of therapy within 24 hours,
      mortality, complete time of remission in days, effectiveness due to increase of
      dosage, relapse on the basis of decrease of dosage, and improvement of symptoms.
      RESULTS: Between the four treatment groups, the complete time of remission was
      significantly different (analysis of variance, F = 4.02; degrees of freedom = 3;
      p = 0.008). In a logistic regression with adjustment for age, gender, and
      severity code, no significant predictor of the treatment for the complete time of
      remission (dichotomized by median) could be found. However, if the premedication
      was a monotherapy with neuroleptics, the complete time of remission was
      significantly shorter with dantrolene monotherapy (t = -2.97; p = 0.004).
      CONCLUSION: The treatment of NMS with drugs that are combined with dantrolene is
      associated with a prolongation of clinical recovery. Furthermore, treatment of
      NMS with dantrolene as monotherapy seems to be associated with a higher overall
      mortality. Therefore, dantrolene does not seem to be the evidence-based treatment
      of choice in cases of NMS but might be useful if premedication consisted of a
      neuroleptic monotherapy.

PMID- 17222341
TI  - Epidemiology and eradication of infectious bovine rhinotracheitis/infectious
      pustular vulvovaginitis (IBR/IPV) virus in Finland.
AB  - BACKGROUND: Infectious bovine rhinotracheitis/infectious pustular vulvovaginitis
      (IBR/IPV) is a significant disease among domestic and wild cattle. The BHV-1
      infection was first detected in Finland in 1970; presumably it was imported in
      1968. The infection reappeared in the large-scale bulk-tank milk surveillances
      which started in 1990, and was eradicated in 1994. Our aim is to describe the
      epidemiology of this infection in Finland, and its eradication. MATERIALS AND
      METHODS: The official sources of pertinent information, the legal basis for the
      disease control and the serological methods for the detection of the infection
      are described. RESULTS AND CONCLUSION: Ten AI bulls were found to be seropositive
      in 1970-1971. The total number of herds with BHV-1 antibody positive animals in
      the large-scale surveillance in 1990 and subsequent epidemiological
      investigations in 1991 was five, and the total number of seropositive animals was
      90. The five herds formed three epidemiological units; semen of at least one bull
      seropositive in 1971 had been used in each unit. This remained the only plausible
      route of infection in each of the three units. Using the 'test and slaughter'
      approach and total stamping out in one herd the infection was eradicated in 1994.

PMID- 17222342
TI  - Regional changes in reactive hyperemic blood flow during exercise training: time
      course adaptations.
AB  - BACKGROUND: Few studies have examined the time-course of localized exercise
      training on regional blood flow in humans. The study examined the influence of
      handgrip exercise training on forearm reactive hyperemic blood flow and vascular
      resistance in apparently healthy men. METHODS: Forearm blood flow and vascular
      resistance were evaluated, in 17 individuals [Age: 22.6 +/- 3.5], in both arms,
      at rest and following 5 minutes of arterial occlusion, using strain gauge
      plethysmography, prior to training (V1) and every week thereafter (V2-5) for 4
      weeks. Handgrip exercise was performed in the non-dominant arm 5 d/wk for 20
      minutes at 60% of maximum voluntary contraction, while the dominant arm served as
      control. RESULTS: Resting HR, BP, and forearm blood flow and vascular resistance
      were not altered with training. The trained arm handgrip strength and
      circumference increased by 14.5% (p = 0.014) and 1.56% (p = 0.03), respectively.
      ANOVA tests revealed an arms by visit interaction for the trained arm for
      reactive hyperemic blood flow (p = 0.02) and vascular resistance (p = 0.009).
      Post-hoc comparison demonstrated increased reactive hyperemic blood flow (p =
      0.0013), and decreased post-occlusion vascular resistance (p = 0.05), following
      the 1st week of training, with no significant changes in subsequent visits.
      CONCLUSION: The results indicate unilateral improvements in forearm reactive
      hyperemic blood flow and vascular resistance following 1 week of handgrip
      exercise training and leveled off for the rest of the study.

PMID- 17222343
TI  - Anti-tumor effect of bisphosphonate (YM529) on non-small cell lung cancer cell
      lines.
AB  - BACKGROUND: YM529 is a newly developed nitrogen-containing bisphosphonate (BP)
      classified as a third-generation BP that shows a 100-fold greater potency against
      bone resorption than pamidronate, a second-generation BP. This agent is,
      therefore expected to be extremely useful clinically for the treatment of
      osteoporosis and hypercalcemia. Recently, YM529 as well as other third-generation
      BPs have also been shown to exert anti-tumor effects against various types of
      cancer cells both in vitro or/and in vivo. In this study, we investigate the anti
      tumor effect of YM529 on non-small cell lung cancer (NSCLC). METHODS: Direct anti
      tumor effect of YM529 against 8 NSCLC cell lines (adenocarcinoma: H23, H1299, NCI
      H1819, NCI-H2009, H44, A549, adenosquamous cell carcinoma: NCI-H125, squamous
      cell carcinoma: NCI-H157) were measured by MTS assay and calculated inhibition
      concentration 50 % (IC50) values. YM529 induced apoptosis of NCI-H1819 was
      examined by DNA fragmentation of 2 % agarose gel electrophoresis and
      flowcytometric analysis (sub-G1 method). We examined where YM529 given effect to
      apoptosis of NSCLC cells in signaling pathway of the mevalonate pathway by
      western blotting analysis. RESULTS: We found that there was direct anti-tumor
      effect of YM529 on 8 NSCLC cell lines in a dose-dependent manner and their IC50
      values were 2.1 to 7.9 microM and YM529 induced apoptosis and G1 arrest cell
      cycle with dose-dependent manner and YM529 caused down regulation of
      phospholyration of ERK1/2 in signaling pathways of NSCLC cell line (NCI-H1819).
      CONCLUSION: Our study demonstrate that YM529 showed direct anti-tumor effect on
      NSCLC cell lines in vitro, which supports the possibility that third-generation
      BPs including YM529 can be one of therapeutic options for NSCLC.

PMID- 17222344
TI  - In silico panning for a non-competitive peptide inhibitor.
AB  - BACKGROUND: Peptide ligands have tremendous therapeutic potential as efficacious
      drugs. Currently, more than 40 peptides are available in the market for a drug.
      However, since costly and time-consuming synthesis procedures represent a problem
      for high-throughput screening, novel procedures to reduce the time and labor
      involved in screening peptide ligands are required. We propose the novel approach
      of 'in silico panning' which consists of a two-stage screening, involving
      affinity selection by docking simulation and evolution of the peptide ligand
      using genetic algorithms (GAs). In silico panning was successfully applied to the
      selection of peptide inhibitor for water-soluble quinoprotein glucose
      dehydrogenase (PQQGDH). RESULTS: The evolution of peptide ligands for a target
      enzyme was achieved by combining a docking simulation with evolution of the
      peptide ligand using genetic algorithms (GAs), which mimic Darwinian evolution.
      Designation of the target area as next to the substrate-binding site of the
      enzyme in the docking simulation enabled the selection of a non-competitive
      inhibitor. In all, four rounds of selection were carried out on the computer; the
      distribution of the docking energy decreased gradually for each generation and
      improvements in the docking energy were observed over the four rounds of
      selection. One of the top three selected peptides with the lowest docking energy,
      'SERG' showed an inhibitory effect with Ki value of 20 microM. PQQGDH activity,
      in terms of the Vmax value, was 3-fold lower than that of the wild-type enzyme in
      the presence of this peptide. The mechanism of the SERG blockage of the enzyme
      was identified as non-competitive inhibition. We confirmed the specific binding
      of the peptide, and its equilibrium dissociation constant (KD) value was
      calculated as 60 microM by surface plasmon resonance (SPR) analysis. CONCLUSION:
      We demonstrate an effective methodology of in silico panning for the selection of
      a non-competitive peptide inhibitor from small virtual peptide library. This
      study is the first to demonstrate the usefulness of in silico evolution using
      experimental data. Our study highlights the usefulness of this strategy for
      structure-based screening of enzyme inhibitors.

PMID- 17222346
TI  - The Adolescent Depression Rating Scale (ADRS): a validation study.
AB  - BACKGROUND: To examine the psychometric properties of the Adolescent Depression
      Rating Scale (ADRS), a new measure was specifically designed to evaluate
      adolescent depression. METHODS: The 11-item clinician-report and 44-item self
      report versions of the ADRS were developed from a qualitative phase involving
      interviews of experts and adolescents. These two instruments were then
      administered to 402 French speaking adolescents with and without depressive
      disorders. Item distribution, internal consistency, convergent validity,
      discriminant validity and factorial structure were assessed. RESULTS: After
      reduction procedures, a 10-item clinician version and a 10-item self-report
      version were obtained. The ADRS demonstrated good internal consistency (alpha
      Cronbach coefficient >.70). It also discriminated better between adolescents with
      and without depression than the Hamilton Depressive Rating Scale and the Beck
      Depression Inventory (BDI-13). CONCLUSION: The ADRS is a useful, short, clinician
      report and self-report scale to evaluate adolescent depression. Further studies
      to replicate our findings and evaluate ADRS sensitivity to effects of treatment
      and psychometric properties in populations of adolescents with several
      psychiatric disorders are warranted.

PMID- 17222347
TI  - A method for the identification of guinea pig blood meal in the Chagas disease
      vector, Triatoma infestans.
AB  - BACKGROUND: In a SINE-based PCR assay, a primer set specific for guinea pig
      genome short interspersed elements DNA was used to test the utility of genomic
      markers for identifying the source of vertebrate blood meals of Triatoma
      infestans. METHODS: The investigation consisted of two assays. In Assay 1, thirty
      six insects, collected from the Province of Zudanez in Chuquisaca, Bolivia were
      frozen 1-40 hours after feeding, under controlled conditions, on guinea pigs. The
      species of the vertebrate host was confirmed from dissection of the posterior
      part of the abdomen of each insect followed by DNA extraction and PCR
      amplification. Assay 2 investigated whether the technique worked under field
      conditions. We analyzed the bloodmeal of 34 insects collected from households and
      peri-domestic structures from communities where wild and captive guinea pigs
      occur. After collection, the insects were maintained at room temperature for 2
      months without feeding and then analyzed. RESULTS: In Assay 1, each of the 36
      insects allowed to feed on guinea pig blood tested positive for guinea pig DNA.
      The guinea pig DNA was reliably identified in as little as 1 hour and up to 40
      hours after feeding. For Assay 2, 8 out of the 34 samples (23%) showed positive
      results with guinea pig specific primers. CONCLUSION: The results in assay 1
      demonstrated that DNA from the vertebrate host can be amplified 1-40 hours post
      feeding from the abdomen of the blood-feeding Chagas disease vector Triatoma
      infestans. The results in assay 2 confirmed that the procedure works on insects
      collected from households and peri-domestic structures and that the source of a
      blood meal can be determined at least 2 months post feeding.

PMID- 17222345
TI  - pkaPS: prediction of protein kinase A phosphorylation sites with the simplified
      kinase-substrate binding model.
AB  - BACKGROUND: Protein kinase A (cAMP-dependent kinase, PKA) is a serine/threonine
      kinase, for which ca. 150 substrate proteins are known. Based on a refinement of
      the recognition motif using the available experimental data, we wished to apply
      the simplified substrate protein binding model for accurate prediction of PKA
      phosphorylation sites, an approach that was previously successful for the
      prediction of lipid posttranslational modifications and of the PTS1 peroxisomal
      translocation signal. RESULTS: Approximately 20 sequence positions flanking the
      phosphorylated residue on both sides have been found to be restricted in their
      sequence variability (region -18...+23 with the site at position 0). The
      conserved physical pattern can be rationalized in terms of a qualitative binding
      model with the catalytic cleft of the protein kinase A. Positions -6...+4
      surrounding the phosphorylation site are influenced by direct interaction with
      the kinase in a varying degree. This sequence stretch is embedded in an
      intrinsically disordered region composed preferentially of hydrophilic residues
      with flexible backbone and small side chain. This knowledge has been incorporated
      into a simplified analytical model of productive binding of substrate proteins
      with PKA. CONCLUSION: The scoring function of the pkaPS predictor can confidently
      discriminate PKA phosphorylation sites from serines/threonines with non
      permissive sequence environments (sensitivity of appoximately 96% at a
      specificity of approximately 94%). The tool "pkaPS" has been applied on the whole
      human proteome. Among new predicted PKA targets, there are entirely
      uncharacterized protein groups as well as apparently well-known families such as
      those of the ribosomal proteins L21e, L22 and L6. AVAILABILITY: The supplementary
      data as well as the prediction tool as WWW server are available at
      http://mendel.imp.univie.ac.at/sat/pkaPS. REVIEWERS: Erik van Nimwegen
      (Biozentrum, University of Basel, Switzerland), Sandor Pongor (International
      Centre for Genetic Engineering and Biotechnology, Trieste, Italy), Igor Zhulin
      (University of Tennessee, Oak Ridge National Laboratory, USA).

PMID- 17222349
TI  - Trapezius transfer to treat flail shoulder after brachial plexus palsy.
AB  - BACKGROUND: After severe brachial palsy involving the shoulder, many different
      muscle transfers have been advocated to restore movement and stability of the
      shoulder. Paralysis of the deltoid and supraspinatus muscles can be treated by
      transfer of the trapezius. METHODS: We treated 10 patients, 8 males and 2
      females, by transfer of the trapezius to the proximal humerus. In 6 patients the
      C5 and C6 roots had been injured; in one C5, C6 and C7 roots; and 3 there were
      complete brachial plexus injuries. Eight of the 10 had had neurosurgical repairs
      before muscle transfer. Their average age was 28.3 years (range 17 to 41), the
      mean delay between injury and transfer was 3.1 years (range 14 months to 6.3
      years) and the average follow-up was 17.5 months (range 6 to 52), reporting the
      clinical and radiological results. Evaluation included physical and radiographic
      examinations. A modification of Mayer's transfer of the trapezius muscle was
      performed. The principal goal of this work was to evaluate the results of the
      trapezius transfer for flail shoulder after brachial plexus injury. RESULTS: All
      10 patients had improved function with a decrease in instability of the shoulder.
      The average gain in shoulder abduction was 46.2 degrees; the gain in shoulder
      flexion average 37.4 degrees. All patients had stable shoulder (no subluxation of
      the humeral head on radiographs). CONCLUSION: Trapezius transfer for a flail
      shoulder after brachial plexus palsy can provide satisfactory function and
      stability.

PMID- 17222348
TI  - Interferon alpha therapy for hepatitis C: treatment completion and response rates
      among patients with substance use disorders.
AB  - BACKGROUND: Individuals with substance use disorders (SUDs) are at increased risk
      for hepatitis C viral infection (HCV), and few studies have explored their
      treatment responses empirically. The objective of this study was to assess
      interferon alpha therapy (IFN) completion and response rates among patients with
      HCV who had a history of comorbid SUDs. More data is needed to inform treatment
      strategies and guidelines for these patients. Using a medical record database,
      information was retrospectively collected on 307,437 veterans seen in the
      Veterans Integrated Service Network 20 (VISN 20) of the Veterans Healthcare
      Administration (VHA) between 1998 and 2003. For patients treated with any type of
      IFN (including regular or pegylated IFN) or combination therapy (IFN and
      ribavirin) who had a known HCV genotype, IFN completion and response rates were
      compared among patients with a history of SUD (SUD+ Group) and patients without a
      history of SUD (SUD- Group). RESULTS: Odds ratio analyses revealed that compared
      with the SUD- Group, the SUD+ Group was equally likely to complete IFN therapy if
      they had genotypes 2 and 3 (73.1% vs. 68.0%), and if they had genotypes 1 and 4
      (39.5% vs. 39.9%). Within the sample of all patients who began IFN therapy, the
      SUD- and SUD+ groups were similarly likely to achieve an end of treatment
      response (genotypes 2 and 3, 52.8% vs. 54.3%; genotypes 1 and 4, 24.5% vs. 24.8%)
      and a sustained viral response (genotypes 2 and 3, 42.6% vs. 41.1%; genotypes 1
      and 4: 16.0% vs. 22.3%). CONCLUSION: Individuals with and without a history of
      SUD responded to antiviral therapy for HCV at similar rates. Collectively, these
      findings suggest that patients who have co-morbid SUD and HCV diagnoses can
      successfully complete a course of antiviral therapy.

PMID- 17222351
TI  - Autoantibodies against the chromosomal passenger protein INCENP found in a
      patient with Graham Little-Piccardi-Lassueur syndrome.
AB  - BACKGROUND: Graham Little - Piccardi - Lassueur (GLPL) syndrome is a rare
      dermatosis characterized by scarring alopecia, loss of pubic and axillary hair,
      and progressive development of variously located follicular papules. We report a
      first case ever of an autoimmune response in a patient suffering from GLPL
      syndrome. METHODS: Immunofluorescence and immunoblot analysis were used in a
      variety of cell cultures including human, monkey, hamster, mouse and bovine cells
      to analyze the presence of autoantibodies in a GLPL patient. RESULTS: The
      autoimmune serum showed a pattern of centromere and spindle microtubule staining
      resembling that of the chromosomal passenger protein complex. By using a complex
      of proteins expressed in baculovirus, immunoblot analysis demonstrated that the
      INCENP protein is a major autoantigen in this patient with GLPL syndrome.
      CONCLUSION: An autoimmune response in GLPL syndrome is reported against the
      INCENP centromere protein. The occasional development of autoimmunity in GLPL
      patients could serve as a test in continuing efforts to detect this disease and
      for a more directed therapy based on the autoantigen response.

PMID- 17222350
TI  - PTTG expression in different experimental and human prolactinomas in relation to
      dopaminergic control of lactotropes.
AB  - BACKGROUND: Pituitary tumor transforming gene (pttg) is a novel oncogene that is
      expressed at higher level in most of the tumors analyzed to date compared to
      normal tissues. Nevertheless, its expression in prolactinomas and its relation
      with the pituitary dopamine receptor 2 (D2R) are not well defined. We sought to
      determine the pituitary level of pttg in three different experimental models of
      prolactinomas with altered dopaminergic control of the pituitary: the
      dopaminergic D2R knockout female mouse, the estrogen-treated rat, and the
      senescent female rat. These three models shared the characteristics of increased
      pituitary weight, hyperprolactinemia, lactotrope hyperplasia and reduced or
      absent dopaminergic action at the pituitary level. We also studied samples from
      human macroprolactinomas, which were characterized as responsive or resistant to
      dopamine agonist therapy. RESULTS: When compared to female wild-type mice,
      pituitaries from female D2R knockout mice had decreased PTTG concentration, while
      no difference in pttg mRNA level was found. In senescent rats no difference in
      pituitary PTTG protein expression was found when compared to young rats. But, in
      young female rats treated with a synthetic estrogen (Diethylstylbestrol, 20 mg)
      PTTG protein expression was enhanced (P = 0.029). Therefore, in the three
      experimental models of prolactinomas, pituitary size was increased and there was
      hyperprolactinemia, but PTTG levels followed different patterns.Patients with
      macroprolactinomas were divided in those in which dopaminergic therapy normalized
      or failed to normalize prolactin levels (responsive and resistant, respectively).
      When pituitary pttg mRNA level was analyzed in these macroprolactinomas, no
      differences were found. We next analyzed estrogen action at the pituitary by
      measuring pituitary estrogen receptor alpha levels. The D2R knockout female mice
      have low estrogen levels and in accordance, pituitary estrogen receptors were
      increased (P = 0.047). On the other hand, in senescent rats estrogen levels were
      slightly though not significantly higher, and estrogen receptors were similar
      between groups. The estrogen-treated rats had high pharmacological levels of the
      synthetic estrogen, and estrogen receptors were markedly lower than in controls
      (P < 0.0001). Finally, in patients with dopamine resistant or responsive
      prolactinomas no significant differences in estrogen receptor alpha levels were
      found. Therefore, pituitary PTTG was increased only if estrogen action was
      increased, which correlated with a decrease in pituitary estrogen receptor level.
      CONCLUSION: We conclude that PTTG does not correlate with prolactin levels or
      tumor size in animal models of prolactinoma, and its pituitary content is not
      related to a decrease in dopaminergic control of the lactotrope, but may be
      influenced by estrogen action at the pituitary level. Therefore it is increased
      only in prolactinomas generated by estrogen treatment, and not in prolactinomas
      arising from deficient dopamine control, or in dopamine resistant compared with
      dopamine responsive human prolactinomas. These results are important in the
      search for reliable prognostic indicators for patients with pituitary adenomas
      which will make tumor-specific therapy possible, and help to elucidate the poorly
      understood phenomenon of pituitary tumorigenesis.

PMID- 17222352
TI  - Sequential gene profiling of basal cell carcinomas treated with imiquimod in a
      placebo-controlled study defines the requirements for tissue rejection.
AB  - BACKGROUND: Imiquimod is a Toll-like receptor-7 agonist capable of inducing
      complete clearance of basal cell carcinoma (BCC) and other cutaneous
      malignancies. We hypothesized that the characterization of the early
      transcriptional events induced by imiquimod may provide insights about
      immunological events preceding acute tissue and/or tumor rejection. RESULTS: We
      report a paired analysis of adjacent punch biopsies obtained pre- and post
      treatment from 36 patients with BCC subjected to local application of imiquimod
      (n = 22) or vehicle cream (n = 14) in a blinded, randomized protocol. Four
      treatments were assessed (q12 applications for 2 or 4 days, or q24 hours for 4 or
      8 days). RNA was amplified and hybridized to 17.5 K cDNA arrays. All treatment
      schedules similarly affected the transcriptional profile of BCC; however, the q12
      x 4 days regimen, associated with highest effectiveness, induced the most
      changes, with 637 genes unequivocally stimulated by imiquimod. A minority of
      transcripts (98 genes) confirmed previous reports of interferon-alpha
      involvement. The remaining 539 genes portrayed additional immunological functions
      predominantly involving the activation of cellular innate and adaptive immune
      effector mechanisms. Importantly, these effector signatures recapitulate previous
      observations of tissue rejection in the context of cancer immunotherapy, acute
      allograft rejection and autoimmunity. CONCLUSION: This study, based on a powerful
      and reproducible model of cancer eradication by innate immune mechanisms,
      provides the first insights in humans into the early transcriptional events
      associated with immune rejection. This model is likely representative of constant
      immunological pathways through which innate and adaptive immune responses combine
      to induce tissue destruction.

PMID- 17222353
TI  - Implantable cardioverter-defibrillators improve survival after coronary artery
      bypass grafting in patients with severely impaired left ventricular function.
AB  - OBJECTIVE: Patients with severe left ventricular (LV) dysfunction have a poor
      long term survival despite complete surgical revascularization. Recent data
      suggests that the use of Implantable Cardioverter-Defibrillator (ICD) improves
      survival in patients with severe LV dysfunction. We compared the survival impact
      of ICD implantation in patients with severe LV dysfunction who underwent CABG.
      METHODS: Between January 1996 and August 2004, 305 patients with LV ejection
      fraction (EF) < or = 25% had CABG surgery at our institution. Demographics of
      patients who had received an ICD (ICD+) in the post -operative period was
      compared to those without ICD (ICD-). Survival was evaluated by the Kaplan-Meier
      method. RESULTS: Of the entire group, 35 (11.5%) patients received an ICD with a
      median of 2 (+/-2) years after CABG. Indication for ICD implantation was clinical
      evidence of non sustained ventricular tachycardia (NSVT). There were no
      differences between the 2 groups with respect to age, gender, NYHA
      classification, number of bypasses, or other co-morbidities. Survival at 1, 3 and
      5 years was 88%, 79%, and 67% for the ICD- group compared to 94%, 89% and 83% for
      the ICD+ group, respectively (figure, p < 0.05). CONCLUSION: Implantation of ICD
      after CABG confers improved short and long term survival benefit to patients with
      severe LV dysfunction. Prophylactic ICD implantation in the setting of severe LV
      dysfunction and CABG surgery should be considered.

PMID- 17222354
TI  - A clade uniting the green algae Mesostigma viride and Chlorokybus atmophyticus
      represents the deepest branch of the Streptophyta in chloroplast genome-based
      phylogenies.
AB  - BACKGROUND: The Viridiplantae comprise two major phyla: the Streptophyta,
      containing the charophycean green algae and all land plants, and the Chlorophyta,
      containing the remaining green algae. Despite recent progress in unravelling
      phylogenetic relationships among major green plant lineages, problematic nodes
      still remain in the green tree of life. One of the major issues concerns the
      scaly biflagellate Mesostigma viride, which is either regarded as representing
      the earliest divergence of the Streptophyta or a separate lineage that diverged
      before the Chlorophyta and Streptophyta. Phylogenies based on chloroplast and
      mitochondrial genomes support the latter view. Because some green plant lineages
      are not represented in these phylogenies, sparse taxon sampling has been
      suspected to yield misleading topologies. Here, we describe the complete
      chloroplast DNA (cpDNA) sequence of the early-diverging charophycean alga
      Chlorokybus atmophyticus and present chloroplast genome-based phylogenies with an
      expanded taxon sampling. RESULTS: The 152,254 bp Chlorokybus cpDNA closely
      resembles its Mesostigma homologue at the gene content and gene order levels.
      Using various methods of phylogenetic inference, we analyzed amino acid and
      nucleotide data sets that were derived from 45 protein-coding genes common to the
      cpDNAs of 37 green algal/land plant taxa and eight non-green algae. Unexpectedly,
      all best trees recovered a robust clade uniting Chlorokybus and Mesostigma. In
      protein trees, this clade was sister to all streptophytes and chlorophytes and
      this placement received moderate support. In contrast, gene trees provided
      unequivocal support to the notion that the Mesostigma + Chlorokybus clade
      represents the earliest-diverging branch of the Streptophyta. Independent
      analyses of structural data (gene content and/or gene order) and of subsets of
      amino acid data progressively enriched in slow-evolving sites led us to conclude
      that the latter topology reflects the true organismal relationships. CONCLUSION:
      In disclosing a sister relationship between the Mesostigmatales and
      Chlorokybales, our study resolves the long-standing debate about the nature of
      the unicellular flagellated ancestors of land plants and alters significantly our
      concepts regarding the evolution of streptophyte algae. Moreover, in predicting a
      richer chloroplast gene repertoire than previously inferred for the common
      ancestor of all streptophytes, our study has contributed to a better
      understanding of chloroplast genome evolution in the Viridiplantae.

PMID- 17222355
TI  - High mobility group A2 is a target for miRNA-98 in head and neck squamous cell
      carcinoma.
AB  - BACKGROUND: HMGA2 expression has been shown to be associated with enhanced
      selective chemosensitivity towards the topoisomerase (topo) II inhibitor,
      doxorubicin, in cancer cells. Although the roles of signaling cascades and
      proteins as regulatory factors in development, neoplasia and adaptation to the
      environment are becoming well established, evidence for the involvement of
      regulatory small RNA molecules, such as microRNAs (miRNAs) as important
      regulators of both transcriptional and posttranscriptional gene silencing is
      presently mounting. RESULTS: Here we report that HMGA2 expression in head and
      neck squamous cell carcinoma (HNSCC) cells is regulated in part by miRNA-98 (miR
      98). Albeit HMGA2 is associated with enhanced selective chemosensitivity towards
      topoisomerase (topo) II inhibitor, doxorubicin in HNSCC, the expression of HMGA2
      is thwarted by hypoxia. This is accompanied by enhanced expression of miRNA-98
      and other miRNAs, which predictably target HMGA2. Moreover, we show that
      transfection of pre-miR-98trade mark during normoxia diminishes HMGA2 and
      potentiates resistance to doxorubicin and cisplatin. These findings implicate the
      role of a miRNA as a key element in modulating tumors in variable
      microenvironments. CONCLUSION: These studies validate the observation that HMGA2
      plays a prominent role in governing genotoxic responses. However, this may only
      represent cells growing under normal oxygen tensions. The demonstration that
      miRNA profiles are altered during hypoxia and repress a genotoxic response
      indicates that changes in microenvironment in eukaryotes mimic those of lower
      species and plants, where, for example, abiotic stresses regulate the expression
      of thousands of genes in plants at both transcriptional and posttranscriptional
      levels through a number of miRNAs and other small regulatory RNAs.

PMID- 17222356
TI  - The vicious cycle of dental fear: exploring the interplay between oral health,
      service utilization and dental fear.
AB  - BACKGROUND: Based on the hypothesis that a vicious cycle of dental fear exists,
      whereby the consequences of fear tend to maintain that fear, the relationship
      between dental fear, self-reported oral health status and the use of dental
      services was explored. METHODS: The study used a telephone interview survey with
      interviews predominantly conducted in 2002. A random sample of 6,112 Australian
      residents aged 16 years and over was selected from 13 strata across all States
      and Territories. Data were weighted across strata and by age and sex to obtain
      unbiased population estimates. RESULTS: People with higher dental fear visited
      the dentist less often and indicated a longer expected time before visiting a
      dentist in the future. Higher dental fear was associated with greater perceived
      need for dental treatment, increased social impact of oral ill-health and worse
      self-rated oral health. Visiting patterns associated with higher dental fear were
      more likely to be symptom driven with dental visits more likely to be for a
      problem or for the relief of pain. All the relationships assumed by a vicious
      cycle of dental fear were significant. In all, 29.2% of people who were very
      afraid of going to the dentist had delayed dental visiting, poor oral health and
      symptom-driven treatment seeking compared to 11.6% of people with no dental fear.
      CONCLUSION: Results are consistent with a hypothesised vicious cycle of dental
      fear whereby people with high dental fear are more likely to delay treatment,
      leading to more extensive dental problems and symptomatic visiting patterns which
      feed back into the maintenance or exacerbation of existing dental fear.

PMID- 17222357
TI  - Noonan syndrome.
AB  - Noonan Syndrome (NS) is characterised by short stature, typical facial
      dysmorphology and congenital heart defects. The incidence of NS is estimated to
      be between 1:1000 and 1:2500 live births. The main facial features of NS are
      hypertelorism with down-slanting palpebral fissures, ptosis and low-set
      posteriorly rotated ears with a thickened helix. The cardiovascular defects most
      commonly associated with this condition are pulmonary stenosis and hypertrophic
      cardiomyopathy. Other associated features are webbed neck, chest deformity, mild
      intellectual deficit, cryptorchidism, poor feeding in infancy, bleeding tendency
      and lymphatic dysplasias. The syndrome is transmitted as an autosomal dominant
      trait. In approximately 50% of cases, the disease is caused by missense mutations
      in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non
      receptor protein tyrosine phosphatase SHP-2 protein. Recently, mutations in the
      KRAS gene have been identified in a small proportion of patients with NS. A DNA
      test for mutation analysis can be carried out on blood, chorionic villi and
      amniotic fluid samples. NS should be considered in all foetuses with
      polyhydramnion, pleural effusions, oedema and increased nuchal fluid with a
      normal karyotype. With special care and counselling, the majority of children
      with NS will grow up and function normally in the adult world. Management should
      address feeding problems in early childhood, evaluation of cardiac function and
      assessment of growth and motor development. Physiotherapy and/or speech therapy
      should be offered if indicated. A complete eye examination and hearing evaluation
      should be performed during the first few years of schooling. Preoperative
      coagulation studies are indicated. Signs and symptoms lessen with age and most
      adults with NS do not require special medical care.

PMID- 17222358
TI  - Comparison of smallpox outbreak control strategies using a spatial metapopulation
      model.
AB  - To determine the potential benefits of regionally targeted mass vaccination as an
      adjunct to other smallpox control strategies we employed a spatial metapopulation
      patch model based on the administrative districts of Great Britain. We counted
      deaths due to smallpox and to vaccination to identify strategies that minimized
      total deaths. Results confirm that case isolation, and the tracing, vaccination
      and observation of case contacts can be optimal for control but only for
      optimistic assumptions concerning, for example, the basic reproduction number for
      smallpox (R0=3) and smaller numbers of index cases ( approximately 10). For a
      wider range of scenarios, including larger numbers of index cases and higher
      reproduction numbers, the addition of mass vaccination targeted only to infected
      districts provided an appreciable benefit (5-80% fewer deaths depending on where
      the outbreak started with a trigger value of 1-10 isolated symptomatic
      individuals within a district).

PMID- 17222360
TI  - [Expression, loss of heterozygosity, and methylation of GNAT1 gene in
      nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: In nasopharyngeal carcinoma (NPC), chromosome 3p21.3 is a
      high frequency deletion region. Evidences from both loss of heterozygosity (LOH)
      and functional studies showed that there may exists NPC-related tumor suppressor
      genes on 3p21.3. This study was to investigate the expression, LOH, and
      methylation of GNAT1 gene, which locates at 3p21.3, in NPC. METHODS: The
      expression of GNAT1 in 33 specimens of primary NPC and 15 specimens of chronic
      nasopharyngitis tissue was detected by reverse transcription-polymerase chain
      reaction (RT-PCR). LOH and promoter methylation status of GNAT1 were examined by
      microsatellites analysis and methylation-specific polymerase chain reaction
      (MSP). RESULTS: GNAT1 was expressed stably in all chronic nasopharyngitis
      tissues, while absent or down-regulated in 24 (72.7%) specimens of NPC (P=0.022).
      LOH analysis showed allele loss of GNAT1 in 3 (15%) specimens of NPC. LOH of
      GNAT1 was correlated to its expression level (P=0.016). Methylation analysis
      showed hypermethylation of GNAT1 promoter in all primary NPC tissues and in 12
      (80%) specimens of chronic nasopharyngitis tissues. CONCLUSIONS: Expression of
      GNAT1 gene is down-regulated or absent in NPC tissues, which may relate to allele
      loss of GNAT1 in NPC, but not relate to its promoter hypermethylation.
      Hypermethylation of GNAT1 may not be oncogenic mechanisms of NPC.

PMID- 17222359
TI  - [Internal target volume definition using four-dimensional CT and dosimetric
      evaluation for hepatocellular carcinoma].
AB  - BACKGROUND & OBJECTIVE: Accurate definition of target volume is difficult in
      three-dimensional conformal radiotherapy (3D CRT) for liver tumors because of the
      wide moving extent of tumors with respiration. This study was to define
      individualized internal target volume (ITV) using four-dimensional computed
      tomography (4D-CT), and compare planning target volumes (PTVs) and dose
      distribution of 3D planning with 4D planning for hepatocellular carcinoma (HCC).
      METHODS: Seven primary HCC patients received 4D-CT scanning. Gross tumor volumes
      (GTVs) and clinical target volumes (CTVs) were contoured on all 10 respiratory
      phases of CT images. The 3D and 4D treatment plans were made for each patient
      using different PTVs, namely, PTV-3D derived from a single CTV plus conventional
      margins; PTV-4D derived from ITV-4D which encompassing all 10 CTVs plus setup
      margins (SM). The two plans were designed at the 20% respiratory phase CT images
      using 3D treatment planning system and compared with respect to PTVs, dose
      distribution to normal tissues, normal tissue complication probability. The
      prescription dose and design of irradiating fields were identical for both plans.
      RESULTS: The average PTV was (417.6+/-197.7) cm(3) in 3D plan and (331.9+/-183.1)
      cm(3) in 4D plan, decreased by 20.50% (12.60%-34.40%). PTV coverage and dose
      uniformity were similar in the 2 plans. 4D plans spared more normal liver,
      kidney, stomach, and small intestine than 3D plans, especially for the liver. The
      V30 and V40 of the liver were lower in 4D plans than in 3D plans (33.59% vs.
      38.77%, 22.62% vs. 27.32%); the mean dose to normal liver was decreased from
      24.13 Gy to 21.5 Gy; liver complication probability was decreased from 21.57% to
      15.86%. Without increasing the normal tissue complication probability, the
      prescription dose was higher in 4D plans than in 3D plans [(54.86+/-2.79) Gy vs.
      (50.57+/-1.51) Gy], increased by 9.72% (4%-16%). CONCLUSIONS: The 3D plans have
      pitfalls of geometric miss or over coverage of target volume. The 4D plans can
      accurately definite target volume to spare more normal tissues and make dose
      escalation as compared with 3D CRT.

PMID- 17222361
TI  - [Screening for mutations in the hotspot mutation regions of PIK3CA gene in
      nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Recent studies showed high frequency of
      phosphatidylinositol 3-kinase catalytic alpha polypeptide (PIK3CA) mutations in
      various human cancers; notably, these mutations frequently locate in the hotspot
      mutation regions of PIK3CA exon 9 and exon 20 with functional significance in
      tumorigenesis, invasion, and anti-apoptosis. This study was to screen for
      mutations in the hotspot mutation regions of PIK3CA in nasopharyngeal carcinoma
      (NPC), and explore the correlation of PIK3CA mutations to tumorigenesis of NPC.
      METHODS: PIK3CA exon 9 and exon 20 in 46 specimens of sporadic primary NPC
      tissues were screened by polymerase chain reaction (PCR)-clone sequencing; those
      in 46 samples of matched NPC peripheral blood and 3 NPC cell lines CNE1, CNE2,
      and SUNE1 were directly sequenced. RESULTS: Among the 46 specimens of NPC, 2
      (4.3%) had point mutation in PIK3CA exon 9 [T1563G (521Asn-->Lys) and A1646G
      (549Asp-->Gly)], 18 had multiple mutations in PIK3CA exon 9 (A1634C-G1658C-del
      1659T), which might be the homologous sequence of Cat Eye Syndrome region on
      22q11.2; none had mutation in PIK3CA exon 20. Moreover, no mutation was detected
      in PIK3CA exon 9 and exon 20 in the 46 matched NPC peripheral blood samples and
      CNE1, CNE2, and SUNE1 cells. CONCLUSIONS: PIK3CA exon 9 and exon 20 rarely mutate
      in NPC. Clone sequencing is more sensitive than direct sequencing in screening
      for somatic mutation. A1634C-G1658C-del 1659T mutations in PIK3CA exon 9,
      detected by clone sequencing, are supposed to be the homologous sequence of Cat
      Eye Syndrome region on 22q11.2 instead of mutations in PIK3CA.

PMID- 17222362
TI  - [Establishment and biological characteristics of lung cancer cell line XWLC-05].
AB  - BACKGROUND & OBJECTIVE: The incidence of lung cancer is high at Xuanwei, Yunnan
      Province, at where the mortality rate of this disease in women is the highest in
      China. This study was to establish a Xuanwei woman lung adenocarcinoma cell line,
      and provide an in vitro experimental model for the study of preventing and
      treating lung cancer. METHODS: The cells derived from a surgical specimen of a
      woman patient with lung cancer were primarily cultured. The biological
      characteristics of the cell line were studied with light and electron
      microscopes, determination of doubling time and growth curve, culturing in soft
      agar, flow cytometry (FCM), chromosome and G-band detection, c-12 multiple tumor
      markers detection, and inoculation in mice. RESULTS: Morphologic study,
      proliferation dynamics, and invasive growth showed that the cultured cells have
      malignant characteristics. Their chromosome numbers ranged from 55 to 69, with a
      mode number of 60-63. The tumor formation rate in mice was 100% after axillary
      transplantation of the cells; the morphology of the tumor cells was similar to
      that of the pathologic specimen of the patient. The cell line was named XWLC-05.
      CONCLUSION: According to the newest rules of establishing a cell line in vitro,
      XWLC-05 is proved to be a new cell line of human lung adenocarcinoma.

PMID- 17222363
TI  - [Reversal effect of antisense RNA targeting human papillomavirus 16 (HPV16) E6E7
      on malignancy of human cervical cancer cell line SiHa].
AB  - BACKGROUND & OBJECTIVE: The ubiquitinated degradation of p53 can be induced by
      human papillomavirus type 16 (HPV16) early gene 6 (E6); the phosphorylated
      inactivation of pRb can be induced by HPV16 E7. They are closely associated with
      the carcinogenesis and progression of cervical cancer. This study was to
      investigate the effects of HPV16 E6E7 antisense RNA on the expression of oncogene
      E6 and E7 and apoptosis of human cervical cancer cell line SiHa harboring HPV16
      genome. METHODS: The antisense sequence of HPV16 E6E7 was cloned into eukaryotic
      expression vector pEGFP to prepare recombinant plasmid containing E6E7AS, which
      was transfected into SiHa cells. The mRNA and protein levels of E6 and E7 gene
      were detected by Western blot and reverse transcription-polymerase chain reaction
      (RT-PCR). Cell proliferation after transfection was evaluated by MTT assay. The
      apoptosis of transfected SiHa cells was assessed by flow cytometry (FCM) and
      confocal laser microscopy. RESULTS: After transfection of HPV16 E6E7 antisense
      RNA, the mRNA and protein levels of HPV16 E6 and E7 in SiHa cells were obviously
      decreased. The proliferation activity of SiHa/E6E7AS cells was significantly
      lower than that of SiHa/EGFP and SiHa cells (0.50+/-0.05 vs. 1.01+/-0.06, 1.28+/
      0.06, P<0.05). The apoptosis rate was significantly higher in SiHa/E6E7AS cells
      than in SiHa/EGFP and SiHa cells [(59.3+/-11.3)% vs. (9.4+/-1.8)%, (2.1+/-0.4)%,
      P<0.05]. The apoptotic cells increased noticeably after transfection. CONCLUSION:
      Down-regulating HPV16 E6 and E7 with antisense RNA induces apoptosis in SiHa
      cells, and may be useful for HPV-associated malignancy gene therapy.

PMID- 17222364
TI  - [Effects of COX-2 gene silencing by shRNA on biological characteristics of human
      hepatocellular carcinoma cell line HepG2].
AB  - BACKGROUND & OBJECTIVE: Cyclooxygenase-2 (COX-2) protein is highly expressed in
      hepatocellular carcinoma (HCC). It may be involved in tumorigenesis and
      development of HCC. This study was to explore the effects of COX-2 short hairpin
      RNA (shRNA) on COX-2 expression in HCC cell line HepG2 and on adhesiveness and
      invasiveness of HepG2 cells in vitro. METHODS: Plasmids WBH1 and WBH2 containing
      2 different sequences of human COX-2 mRNA coding region were constructed, and
      transfected into HepG2 cells, respectively. The expression of COX-2 was detected
      by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot at
      24, 48, 72 and 96 h after transfection. At 48 h after transfection, the
      adhesiveness of HepG2 cells to extracellular matrix matrigel was detected using
      MTT assay. Invasiveness was measured by Transwell experiment. RESULTS: The
      transfection rate in HepG2 cells was about 60%. The inhibition rates of COX-2
      mRNA expression in HepG2 cells were 18.5%, 88.6%, 52.8%, and 42.4% at 24, 48, 72
      and 96 h after transfection of plasmid WBH1 (P<0.01); the inhibition rates of COX
      2 protein expression were 10.2%, 80.5%, 45.3%, and 39.0%, respectively (P<0.01).
      Plasmid WBH2 had no significant inhibitory effect on COX-2 expression in HepG2
      cells (P>0.05). The adhesion rate of WBH1-transfected cells was obviously reduced
      by 47.4% of control cells [(6.0+/-0.4)% vs. (11.4+/-0.2)%, P<0.01]. The cell
      number that infiltrated Transwell membrane in WBH1-transfected group was
      significantly reduced by 63.7% of control group (8.25+/-1.50 vs. 22.75+/-1.70,
      P<0.01). WBH2 had no obvious effects on adhesiveness and invasiveness of HepG2
      cells. CONCLUSION: COX-2 shRNA can inhibit the adhesiveness and invasiveness of
      HepG2 cells through intervening the expression of COX-2.

PMID- 17222365
TI  - [Effect of bone marrow stromal cells transfected with interleukin 18 on growth of
      intracranial glioma in rats].
AB  - BACKGROUND & OBJECTIVE: Because of the invasion and immune escape
      characteristics, surgical resection, radiotherapy, and chemotherapy had no
      definite curative effects on intracranial glioma. Because bone marrow stromal
      cells (BMSCs) can track migrating cells, and interleukin 18 (IL-18) can enhance
      antitumor immune reaction, this study was to explore the effect of IL-18
      transfected BMSCs on growth of glioma in rats. METHODS: Pure BMSCs were obtained
      by culturing rat bone marrow cells and identified by flow cytometry (FCM). BMSCs
      were transfected with retrovirus LXSN/IL-18 to prepare BMSCs/IL-18. IL-18 genetic
      transcription and expression were assessed by reverse transcription-polymerase
      chain reaction (RT-PCR) and immunofluorescence. The characteristic variations of
      BMSCs were detected by MTT assay, FCM, and immunofluorescence. The effect of
      BMSCs/IL-18 on activation of T cells was evaluated by ELISA. Glioma-bearing rats
      were divided into BMSCs group, BMSCs/IL-18 group, PBS group, and control group
      and received relevant treatments. The effect of BMSCs/IL-18 on growth of glioma
      was observed. RESULTS: IL-18 gene was expressed stably in BMSCs/IL-18. The
      proliferation speed of BMSCs/IL-18 was slower than that of BMSCs. The secretion
      of interferon-gamma (IFN-gamma) from rat spleen lymphocytes in BMSCs/IL-18 group
      was 9 times more than that in BMSCs group. Tumor volume was (18.26+/-6.84) mm(3)
      in BMSCs group, (6.37+/-1.52) mm(3) in BMSCs/IL-18 group, (22.48+/-6.02) mm(3) in
      PBS group, and (21.06+/-5.83) mm(3) in control group; survival time of the rats
      was (25.3+/-6.4) days, (84.7+/-16.3) days, (21.6+/-4.7) days, and (22.5+/-6.2)
      days, respectively. After transplantation of BMSCs/IL-18, CD4(+) T cells in
      glioma were increased to 37.7+/-3.5 and CD8(+) T cells were increased to 32.3+/
      4.5 in each field of view (x200). CONCLUSION: BMSCs/IL-18 could express IL-18
      gene stably, and have definite therapeutic effect on glioma in rats.

PMID- 17222366
TI  - [Detection and significance of APC gene promoter hypermethylation in serum of
      breast cancer patients].
AB  - BACKGROUND & OBJECTIVE: Detection of circulating tumor markers is one of current
      hot spots in tumor research. Free tumor DNA may exist in the peripheral blood of
      malignant tumor patients. Identical DNA mutations existing in both peripheral
      serum and primary tumor are found in many kinds of malignant tumors. This study
      used adenomatous polyposis coli (APC) gene promoter hypermethylation as a tumor
      marker to investigate the correlations of free tumor DNA to primary tumor and
      clinicopathologic features of breast cancer. METHODS: The methylation status of
      APC gene in tumor tissue, paracancer normal tissue, and paired peripheral serum
      from 84 patients with breast cancer and 10 patients with benign breast diseases
      were detected by methylation-specific polymerase chain reaction (MSP). RESULTS:
      The detection rate of APC gene promoter hypermethylation was 45.2% in tumor
      tissues and 31.0% in paired peripheral sera. APC gene hypermethylation in
      peripheral serum was significantly correlated to that in tumor tissue (r=0.977,
      P=0.002). The sensitivity of detecting APC gene hypermethylation in peripheral
      serum was 68.4%; the specificity was 97.8%. The aberrant methylation of APC gene
      in tumor tissue and peripheral serum had no correlation to patients' age, tumor
      stage, tumor size, histological type, and receptor status (P>0.05). No aberrant
      methylation of APC gene was found in the serum samples from healthy control and
      the patients without gene methylation in tumor tissue. CONCLUSION: The aberrant
      tumor gene methylation in peripheral serum of breast cancer patients is
      significantly correlated to that in primary tumor.

PMID- 17222367
TI  - [Correlation of p38 mitogen-activated protein kinase signal transduction pathway
      to uPA expression in breast cancer].
AB  - BACKGROUND & OBJECTIVE: p38 mitogen-activated protein kinase (p38MAPK) signal
      transduction pathway regulates the expression of various metastasis-related
      genes. Urokinase-type plasminogen activator (uPA) plays an important role in
      cancer invasion and metastasis. This study was to explore the correlation of
      p38MAPK signal transduction pathway to uPA expression in breast cancer. METHODS:
      SP immunohistochemistry was used to test the expression of p-p38, p-Akt, p-Erk,
      and uPA in 60 specimens of breast cancer. Western blot was used to detect the
      protein levels of p-p38 and uPA in breast cancer MDA-MB-231 and MCF-7 cells and
      the protein level of uPA in MDA-MB-231 cells after blocking p38MAPK signal
      transduction pathway by SB203580, a specific inhibitor of p38MAPK. The
      correlations of p-p38, p-Akt, p-Erk, and uPA expression to the clinicopathologic
      characteristics of breast cancer, and the correlations of p-p38, p-Akt, and p-Erk
      expression to uPA expression were analyzed. The mechanism of p38MAPK signal
      transduction pathway regulating the protein expression of uPA in breast cancer
      cells was investigated. The correlation of p-p38 and uPA expression to prognosis
      of breast cancer was analyzed. RESULTS: The positive rates of p-p38, p-Akt, p
      Erk, and uPA proteins in breast cancer tissues were 56.7%, 95.0%, 93.3%, and
      60.0%, respectively. The expression of p-p38 was positively correlated to the
      expression of uPA (r=0.316, P<0.05), while the expression of p-Akt and p-Erk was
      not related to uPA expression. The expression of p-p38 and uPA was correlated to
      lymph node metastasis and TNM stage (P<0.05), but not to patients' age and tumor
      size (P>0.05). The expression of p-Akt and p-Erk were correlated to lymph node
      metastasis (P<0.05), but not to TNM stage, patients' age, and tumor size
      (P>0.05). The protein levels of p-p38 and uPA in MDA-MB-231 cells were higher
      than that in MCF-7 cells. SB203580 concentration-dependently inhibited p38MAPK
      pathway and induced uPA protein expression. The expression of p-p38 and uPA was
      negatively correlated to prognosis of breast cancer (log-rank=4.98, 5.40,
      P=0.026, 0.020). CONCLUSIONS: p38MAPK signal transduction pathway might improve
      breast cancer progression by up-regulating uPA expression, and might be an
      important route in invasion and metastasis of breast cancer. p-p38 and uPA might
      help to evaluate prognosis of breast cancer.

PMID- 17222369
TI  - [Flt-3/ITD mutation in pediatric leukemia and its clinical significance].
AB  - BACKGROUND & OBJECTIVE: Flt-3 internal tandem duplication (Flt-3/ITD) in
      transmembrane region is the most frequently identified mutation in Flt-3 gene,
      which is the most frequently happened in acute myeloid leukemia (AML) and
      correlated to prognosis. This study was to explore the correlation of Flt-3/ITD
      mutation to the occurrence of pediatric leukemia, and analyze its clinical
      significance. METHODS: Flt-3/ITD mutation status in bone marrow samples from 302
      children with leukemia, including 122 cases of AML, 124 cases of acute
      lymphoblastic leukemia (ALL), 17 cases of juvenile chronic myelogenous leukemia
      (JCML), and 39 cases of myelodysplastic syndromes (MDS), were examined by
      polymerase chain reaction (PCR) and sequencing. RESULTS: Of the 122 AML patients,
      98 (80.32%) had Flt-3 gene products in bone marrow. Flt-3/ITD mutation was
      detected in 21 (17.21%) of the 122 patients; the mutation rates were 42.86% (3/7)
      in M0, 22.22% (2/9) in M1, 12.90% (4/31) in M2, 44.44% (8/18) in M4, and 15.38%
      (4/26) in M5. Of the 124 ALL patients, 72 (58.06%) had Flt-3 gene products in
      bone marrow. Flt-3/ITD mutation was found in 2 (1.61%) of the 72 patients. DNA
      sequencing and Blast alignment revealed that ITD within exon 11 existed in all
      samples, with various duplication regions and lengths (24-95 bp). No Flt-3/ITD
      mutation was found in MDS patients and JCML patients. Of the 19 AML patients with
      Flt3/ITD mutation, the median survival time was 13.5 months (0-47 months), which
      was significantly shorter than that of the patients without Flt-3/ITD mutation
      (P<0.05). The percentage of neutrophils in peripheral blood was similar in Flt
      3/ITD-positive and Flt-3/ITD-negative patients (P>0.05). Chromosome karyotype
      analysis showed chromosome abnormity, including t(11; 12)(p15; q13), inv16(q21;
      q23), and t(6; 9)(p23; q23), in 3 AML patients with Flt-3/ITD. CONCLUSIONS: Flt
      3/ITD mutations are usually detected in AML, seldom in ALL, not in MDS and JCML.
      Flt-3/ITD mutation is correlated to AML onset and progress. Flt-3/ITD is a
      significant marker to analyze AML prognosis.

PMID- 17222368
TI  - [Infection status and clinical significance of Epstein-Barr virus in pediatric
      leukemia---a report of 35 cases].
AB  - BACKGROUND & OBJECTIVE: Epstein-Barr virus (EBV) is associated with genesis of
      many human tumors. This study was to detect EBV infection in pediatric leukemia,
      and to explore its clinical significance. METHODS: EBV DNA in peripheral blood
      mononuclear cells in 35 pediatric leukemia patients, including 26 cases of acute
      lymphoblastic leukemia (ALL) (24 received initial treatment and 2 received
      retreatment), 8 cases of acute non-lymphocytic leukemia (ANLL) and 1 case of
      chronic lymphocytic leukemia (CLL), and in 14 healthy children was detected by
      fluorescent quantitative polymerase chain reaction (FQ-PCR). Its clinical
      significance was analyzed according to the clinical manifestations, prednisone
      sensitivity test, and complete remission (CR) rate after induction chemotherapy.
      RESULTS: EBV DNA was detected in 8 (22.86%) of the 35 pediatric leukemia
      patients. The positive rate of EBV DNA was 26.92% (7/26) in ALL with quantity of
      (5.144+/-6.91)x10(5) copies/ml, and 12.5% (1/8) in ANLL patients with quantity of
      4.031x10(3) copies/ml. No EBV DNA was detected in CLL patients and healthy
      controls. The occurrence rates of peripheral leukocytosis and hepatosplenomegaly
      were significantly higher in the patients with EBV infection than in the patients
      without EBV infection (P <0.001). In ALL, the rate of no response to prednisone
      was significantly higher in the patients with EBV infection than in the patients
      without EBV infection (100% vs. 26.32%, P =0.001); CR rate after induction
      chemotherapy was significantly lower in the patients with EBV infection than in
      the patients without EBV infection (28.57% vs. 84.21%, P=0.003). In ANLL, the
      differences of CR rate and relapse rate were not significant between the patients
      with and without EBV infection (P=0.5). CONCLUSIONS: Pediatric leukemia patients
      with EBV infection have higher incidence of peripheral leukocytosis and
      hepatosplenomegaly. ALL patients with EBV infection have poor prednisone response
      and low CR rate.

PMID- 17222370
TI  - [Radiation-induced temporomandibular joint damage in nasopharyngeal carcinoma
      patients after intensity-modulated radiotherapy].
AB  - BACKGROUND & OBJECTIVE: Radiation-induced temporomandibular joint damage is a
      kind of common complication after radiotherapy for nasopharyngeal carcinoma (NPC)
      patients. Trimus is the main symptom of this damage, and severely affects the
      quality of life of the patients. This study was to evaluate radiation-induced
      temporomandibular joint damage in NPC patients treated with intensity-modulated
      radiotherapy (IMRT), and analyze its affecting factors. METHODS: From Feb. 2001
      to Feb. 2003, 148 naive NPC patients were treated with IMRT by 2.27-2.80 Gy per
      fraction at a total dose of 63-77 Gy within 31-86 days. The distance between 2
      dens incisivus medialis (DDIM) was measured before radiotherapy, and 6 months, 1
      year, 2 years, and 3 years after radiotherapy, respectively. RESULTS: The overall
      1-, 2-, and 3-year survival rates were 97.26%, 94.83%, and 92.04%. The
      irradiation dose to temporomandibular joint was 17.9-51.36 Gy. Seven (4.73%)
      patients suffered from grade I-II temporomandibular joint damage after IMRT; no
      patient had grade III-IV temporomandibular joint damage. CONCLUSIONS: IMRT can
      spare the temporomandibular joint from high dose irradiation. The risk of
      radiation-induced severe temporomandibular joint damage in NPC patients after
      IMRT is low.

PMID- 17222371
TI  - [Helical double-phase CT scan imaging features of hepatocellular carcinoma and
      pathology of false-positive lesions].
AB  - BACKGROUND & OBJECTIVE: The helical double-phase CT scan imaging features of
      hepatocellular carcinoma (HCC) overlap those of other hepatic lesions. This study
      was to investigate the helical double-phase CT scan imaging features of HCC to
      improve diagnosis accuracy. METHODS: Double-phase CT data and pathologic data of
      52 HCC patients, received resection in Cancer Center of Sun Yat-sen University
      from Dec. 2000 to Dec. 2002, were analyzed. The double-phase CT features of HCC
      lesions were summarized. The pathology of false-positive lesions was analyzed.
      RESULTS: CT scan showed 56 lesions in the 52 patients: 51 were cancer lesions,
      including 49 HCC lesions and 2 mixed lesions of HCC and cholangioma, 5 were false
      positive lesions. Arterial phase of these HCC lesions showed obvious
      heterogeneous enhancement, and the portal vein phase showed heterogeneous low
      dense. Necrosis was seen in all massive lesions, but was seldom seen in nodular
      and small lesions. Most lesions had clear borders and amicula. The pathologic
      diagnoses of the 5 false-positive lesions were hepatic cirrhosis with
      hepatocellular nodular hyperplasia, regenerative nodule, hepatic cirrhosis, bile
      duct calculus companied with inflammatory reaction, and fibrosis hyperplasia.
      CONCLUSIONS: Helical double-phase CT scan can be used to diagnose typical HCC
      lesions. There are no obvious differences in helical double-phase CT scan between
      HCC lesions and false-positive lesions. The diagnosis of HCC must be based on
      clinical information, follow-up or biopsy.

PMID- 17222372
TI  - [Role of 16 slices spiral CT angiography with 3-dimensional CT and CT virtual
      endoscopy in detecting blood supply of lung carcinoma].
AB  - BACKGROUND & OBJECTIVE: Angiography, a common method in evaluating blood supply
      of lung carcinoma, is invasive and complicated, with low success rate for
      bronchial artery, and could not assure to show all supply blood vessels at a
      time. This study was to explore clinical value of 16 slices spiral CT angiography
      with 3-dimensional CT (3DCT) and CT virtual endoscopy (CTVE) in diagnosing and
      evaluating supply blood vessels and blood supply of lung carcinoma, so as to find
      a non-invasive, safe, simple and effective method in diagnosing blood supply of
      lung carcinoma. METHODS: A total of 72 patients with pathologically proved lung
      carcinoma underwent 16 slices spiral CT angiography with 3DCT. Volume rendering
      (VR), maximum intensity projection (MIP), and surface shaded display (SSD) of
      supply blood vessels of lung carcinoma were used as 3DCT models. CTVE of
      bronchial artery was performed in 25 patients. Color VR of tumor lesion was
      performed in all patients. RESULTS: Supply blood vessels were showed in 68
      patients, 59 of them showed only bronchial artery, 5 showed intercostals
      arteries, and 4 showed mixed types, including bronchial artery, intercostals
      arteries, or branch arteries of subclavian artery. The bronchial artery entered
      into enlarged mediastinal lymph nodes in 4 patients. CTVE well displayed the
      orifice and lumen of bronchial arteries in the 25 patients. The extent of red
      color of tumor lesion on VR color image were divided into 4 types: no color
      (n=11), light red (n=17), moderate red (n=32), and heavy red (n=12); the added CT
      values of tumor lesion after enhanced CT were (6.16+/-2.23) Hu, (15.71+/-3.13)
      Hu, (25.47+/-2.71) Hu, and (44.31+/-19.68) Hu, respectively. The corresponding
      rate between enhanced type and distributive type of red color on color VR was
      86.1%. CONCLUSIONS: The 16 slices spiral CT angiography with 3DCT and CTVE could
      show clearly supply blood vessels and blood supply of lung carcinoma. It is a non
      invasive, simple and effective method in evaluating and diagnosing blood supply
      of lung carcinoma.

PMID- 17222373
TI  - [Diagnostic values of CT perfusion imaging in pulmonary masses].
AB  - BACKGROUND & OBJECTIVE: Blood flow patterns with CT perfusion imaging (CTPI) had
      been innovated to delineate abnormal hemodynamic lesions in the liver, brain, and
      kidney. This study was to evaluate the blood flow patterns of pulmonary masses by
      CTPI, and determine the value of CTPI in differential diagnosis among benign,
      malignant, and inflammatory masses. METHODS: Fifty-two patients with previously
      diagnosed pulmonary masses (37 with malignant masses, 7 with benign masses, and 8
      with inflammatory masses) underwent dynamic CTPI. Time-density curves (TDC) of
      artery, vein, and pulmonary masses as well as mass perfusion images and
      parameters including perfusion volume (PV), peak height (PH), mean transit time
      (MTT) and blood volume (BV) were obtained by Phlips CT-perfusion software.
      RESULTS: The values of PV, PH, and BV were significantly higher in malignant
      masses and active inflammatory masses than in benign masses [(27.63+/-15.06)
      ml.min(-1).ml(-1) and (30.80+/-20.33) ml.min(-1).ml(-1) vs. (11.81+/-3.74)
      ml.min(-1).ml(-1), (28.46+/-12.07) Hu and (32.15+/-15.89) Hu vs. (10.41+/-3.77)
      Hu, (21.64+/-10.97) ml/100 g and (28.38+/-14.55) ml/100 g vs. (10.61+/-5.33)
      ml/100 g, P<0.01]. However, the differences of MTT among malignant, inflammatory,
      and benign masses were not significant [(28.39+/-21.66) s, (25.91+/-14.57) s, and
      (29.86+/-13.57) s, P=0.928]. No significant differences in the 4 parameters were
      found between malignant and inflammatory masses. When PV >20 ml.min(-1).ml(-1)
      and pH >15 Hu were set as a diagnostic threshold (excluded active inflammatory
      masses), the sensitivity, specificity, and accuracy were 91.9%, 100%, and 84.1%,
      respectively. CONCLUSION: CT perfusion imaging provides quantitative information
      about blood flow patterns of pulmonary masses and is an applicable diagnostic
      method for differentiating pulmonary masses.

PMID- 17222374
TI  - [Primary breast lymphoma--a report of 27 cases with literature review].
AB  - BACKGROUND & OBJECTIVE: Primary breast lymphoma (PBL) is an uncommon disease with
      poor clinical outcome. This study was to investigate clinicopathologic features
      and optimal treatment of PBL. METHODS: Clinical records of 27 PBL patients,
      treated in Cancer Center of Sun Yat-sen University from 1976 to 2005, were
      reviewed. RESULTS: Of the 27 patients, 26 were women and 1 was man, with the age
      ranged from 12 to 84; 18 were at stage IE, 6 at stage IIE, and 3 at stage
      III/IVE; according to the WHO 2001 lymphoma classification system, 22 had B-cell
      lymphoma (including 17 cases of diffuse large B-cell lymphoma, 2 cases of mucosa
      associated lymphoid tissue lymphoma, 1 case of marginal zone lymphoma, and 2
      cases of unclassified B-cell lymphoma), 3 had peripheral T-cell lymphoma, and 2
      had unclassified lymphoma. Of the 27 patients, 8 received mastectomy and
      chemotherapy, 12 received excision of the breast lesion and chemotherapy (the 5
      year overall survival rates were 23% and 58%, P=0.006), 5 received chemotherapy
      alone, and 2 received lesion excision alone; 24 achieved complete remission (CR)
      after scheduled treatment, 1 achieved partial remission (PR), and 2 patients had
      progressive disease (PD). With a follow-up of 10 years and median 38 months, the
      5-year overall and disease-free survival rates of the 27 patients were 47% and
      23%, respectively. As to the 20 patients with high or moderate grade diseases
      (diffuse large B-cell lymphoma and peripheral T-cell lymphoma), the 5-year
      overall and disease-free survival rates were 48% and 27%, respectively. Sixteen
      patients had tumor relapse during the follow-up in the homolateral breast (6
      cases), controlateral breast (4 cases), central nerve system (CNS) (3 cases),
      bone marrow (1 case), and lymph nodes (2 cases). CONCLUSIONS: The main subtypes
      of PBL are diffuse large B-cell lymphoma and peripheral T-cell lymphoma. The
      effect of radical operation is limited in PBL; the optimal sequence is lumpectomy
      followed by standard anthracycline-based regimens and radiotherapy. PBL tends to
      relapse to CNS, therefore, CT or MR image of CNS is necessary during follow-up.

PMID- 17222375
TI  - [Expression and clinical significance of vascular endothelial growth factor C and
      D in nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Recently, vascular endothelial growth factor-C (VEGF-C)
      and -D (VEGF-D) have been identified as specific lymphangiogenic factors, and
      their overexpression are related to lymphatic metastasis. This study was to
      investigate the expression and clinical significance of VEGF-C and VEGF-D in
      nasopharyngeal carcinoma (NPC). METHODS: The expression of VEGF-C, VEGF-D,
      vascular endothelial growth factor receptor-3 (VEGFR-3), and CD34 in 66 specimens
      of NPC and 19 specimens of nasopharyngitis tissue were detected by SP
      immunohistochemistry. Lymphatic microvessel density (LMVD) and microvessel
      density (MVD) were calculated. RESULTS: The high expression rate of VEGF-C was
      significantly higher in NPC than in nasopharyngitis tissues (54.5% vs. 26.3%,
      P<0.05). The high expression rate of VEGF-C was significantly higher in the NPC
      with regional lymph node metastasis than in those without, and higher in the NPC
      with high T stage than in those with low T stage (P<0.05). Both univariate and
      multivariate logistic regression analyses showed that high expression of VEGF-C
      was correlated to regional lymph node metastasis (P<0.05), but not to age, sex, 5
      year survival, LMVD, and MVD (P>0.05). The positive rate of VEGF-D was
      significantly higher in NPC tissues than in adjacent non-cancerous tissues (69.7%
      vs. 42.1%, P<0.05). In NPC tissues, VEGF-D expression had no correlations to age,
      sex, T stage, regional lymph node metastasis, LMVD, and MVD (P>0.05), but was
      positively related to high expression of VEGF-C. The 5-year survival rate was
      significantly lower in VEGF-D-positive NPC than in VEGF-D-negative NPC (50.0% vs.
      85.0%, P<0.05). CONCLUSION: In NPC, high expression of VEGF-C is closely
      correlated to regional lymph node metastasis; positive expression of VEGF-D shows
      no correlation to regional lymph node metastasis, but is positively related to
      high expression of VEGF-C and closely correlated to 5-year survival rate.

PMID- 17222376
TI  - [Expression and significance of MCM4 in esophageal cancer].
AB  - BACKGROUND & OBJECTIVE: MCM4 belongs to minichromosome maintenance (MCM) protein
      family. It is a DNA replication licensing factor. This study was to explore the
      expression and significance of MCM4 in esophageal squamous cell cancer (ESCC).
      METHODS: The expression of MCM4 in 60 specimens of ESCC, paracancer esophageal
      epithelia, and distant normal esophageal epithelia was detected by reverse
      transcription-polymerase chain reaction (RT-PCR). The Correlations of MCM4
      expression to clinicopathologic features of the 60 ESCC patients were analyzed.
      RESULTS: The positive rate of MCM4 was significantly higher in ESCC than in
      paracancer esophageal epithelia (65.0% vs. 33.3%, P<0.001); MCM4 was not
      expressed or weakly expressed in distant normal esophageal epithelia. The
      positive rate of MCM4 was significantly higher in stage T3 ESCC than in stage T1
      ESCC (73.7% vs. 25.0%, P<0.05). The expression of MCM4 had no correlations to
      grade, lymph node metastasis, sex, and age. CONCLUSION: The expression of MCM4
      might be related to the pathologic stage of ESCC.

PMID- 17222377
TI  - [Human esophageal carcinoma antigens screened by serologic analysis of
      recombinant cDNA expression libraries (SEREX)].
AB  - BACKGROUND & OBJECTIVE: In malignant transformation, mutant gene products and
      dysregulated proteins can become tumor antigens and activate immunoreactions.
      Therefore, auto-antibodies exist in sera of cancer patients. Serologic analysis
      of recombinant cDNA expression libraries (SEREX) using autologous and allogenic
      patient sera provides a powerful approach to identify tumor antigens. This study
      was to identify esophageal cancer antigens with SEREX for serologic diagnosis,
      gene therapy, and immune therapy. METHODS: Expression library of cDNA from
      esophageal squamous cell carcinoma was constructed. SEREX screened out 21
      positive clones from the 1.6x10(6) clones in the established library. The 21
      positive clones were subcloned to monoclonality and submitted to in vivo excision
      of pBluescript phagemids. The nucleotide sequences of cDNA inserts were analyzed
      with DNASIS and BLAST software on EMBL and GenBank. According to the
      bioinformatics analyses, serologic immunoreactions of 4 colons in 10 samples of
      esophageal cancer serum and 10 samples of normal control serum were further
      detected by SADA. RESULTS: Of the 21 positive clones, 4 had no homology to any
      known genes, 17 were known fragments which were defined as antigens of esophageal
      cancer for the first time. The serologic immunoreaction rates of 4 selected
      antigens, including Ribosomal protein S4, and so on, were 40%, 60%, 70%, and 30%,
      respectively, in cancer sera, and 0%, 10%, 20%, and 20%, respectively, in normal
      sera. CONCLUSIONS: Antigens, such as Ribosomal protein S4, are frequently
      involved in serologic immunoreactions of esophageal cancer. The 21 antigens
      identified by the present study can be used as potential targets for gene therapy
      and serologic biomarkers of esophageal cancer.

PMID- 17222378
TI  - [Advances in molecular oncologic pathology].
AB  - Molecular oncologic pathology is a relatively new discipline. It integrates
      molecular biology with oncologic pathology. Different from the morphology-based
      traditional diagnostic pathology, molecular oncologic pathology relies on
      molecular evidences. Complementary to and based on traditional diagnostic
      pathology, molecular oncologic pathology further predicts the biological behavior
      of a given tumor and also guides the therapy. This review elaborated the basic
      concepts and theories of molecular oncologic pathology. It listed several cases
      to illustrate the clinical applications of molecular oncologic pathology, and to
      explain how molecular oncologic pathology assists clinicians in cancer diagnosis,
      treatment, prognostication, and most importantly, cancer prevention.

PMID- 17222379
TI  - [Top performance--at all costs].

PMID- 17222380
TI  - Recent progress in the determination of solid surface tensions from contact
      angles.
AB  - Advancing contact angles of different liquids measured on the same solid surface
      fall very close to a smooth curve when plotted as a function of liquid surface
      tension, i.e., gamma(lv)costheta versus gamma(lv). Changing the solid surface,
      and hence gamma(sv), shifts the curve in a regular manner. These patterns suggest
      that gamma(lv)costheta depends only on gamma(lv) and gamma(sv). Thus, an
      "equation of state for the interfacial tensions" was developed to facilitate the
      determination of solid surface tensions from contact angles in conjunction with
      Young's equation. However, a close examination of the smooth curves showed that
      contact angles typically show a scatter of 1-3 degrees around the curves. The
      existence of the deviations introduces an element of uncertainty in the
      determination of solid surface tensions. Establishing that (i) contact angles are
      exclusively a material property of the coating polymer and do not depend on
      experimental procedures and that (ii) contact angle measurements with a
      sophisticated methodology, axisymmetric drop shape analysis (ADSA), are highly
      reproducible guarantees that the deviations are not experimental errors and must
      have physical causes. The contact angles of a large number of liquids on the
      films of four different fluoropolymers were studied to identify the causes of the
      deviations. Specific molecular interactions at solid-vapor and/or solid-liquid
      interfaces account for the minor contact angle deviations. Such interactions take
      place in different ways. Adsorption of vapor of the test liquid onto the solid
      surface is apparently the only process that influences the solid-vapor
      interfacial tension (gamma(sv)). The molecular interactions taking place at the
      solid-liquid interface are more diverse and complicated. Parallel alignment of
      liquid molecules at the solid surface, reorganization of liquid molecules at the
      solid-liquid interface, change in the configuration of polymer chains due to
      contact with certain probe liquids, and intermolecular interactions between solid
      and liquid molecules cause the solid-liquid interfacial (gamma(sl)) tension to be
      different from that predicted by the equation of state, i.e., gamma(sl) is not a
      precise function of gamma(lv) and gamma(sv). In other words, the experimental
      contact angles deviate from the "ideal" contact angle pattern. Specific criteria
      are proposed to identify probe liquids which eliminate specific molecular
      interactions. Octamethylcyclotetrasiloxane (OMCTS) and
      decamethylcyclopentasiloxane (DMCPS) are shown to meet those criteria, and
      therefore are the most suitable liquids to characterize surface tensions of low
      energy fluoropolymer films with an accuracy of +/-0.2 mJ/m2.

PMID- 17222381
TI  - The role of surfactants in dispersion of carbon nanotubes.
AB  - The discovery of carbon nanotubes offers exciting opportunities for the
      development of novel high property materials. Disaggregation and uniform
      dispersion are critical challenges that must be met to successfully produce such
      high property materials, since carbon nanotubes tend to self-associate into micro
      scale aggregates. This results in products with inferior mechanical and electric
      performance. Recognizing this problem, extensive research has been reported in
      the literature on development of dispersion technologies based on both mechanical
      and chemical approaches. Here, we review recent progress and advances that have
      been made on dispersion of carbon nanotubes in aqueous and organic media by non
      covalent adsorption of surfactants and polymers. Carbon nanotube structure,
      properties and mainly self-assembly are discussed in detail.

PMID- 17222382
TI  - Long-term follow-up of high myopic foveoschisis: natural course and surgical
      outcome.
AB  - PURPOSE: To determine the natural evolution and surgical indications of myopic
      foveoschisis (MF), which are still poorly documented, and the factors that
      predict poor prognosis. DESIGN: Retrospective observational case series. METHODS:
      Twenty-nine operated and nonoperated cases of MF (29 eyes of 23 patients) were
      studied. All eyes underwent repeated examinations, including optical coherence
      tomographic (OCT) recordings, during a mean follow-up of 31.2 months. Special
      attention was paid to the evolution of visual acuity (VA) and to the thickness of
      foveoschisis. RESULTS: Mean refraction was -14.4 diopters, and mean axial length
      was 29.1 mm. OCT scans revealed that the foveoschisis was associated with macular
      anomalies: a premacular structure in 13 (44.8%) of 29 eyes, a foveal detachment
      in 10 (34.5%) of 29 eyes, and a lamellar macular hole in six (20.7%) of 29 eyes.
      Isolated foveoschisis was found in four eyes (13.8%). During follow-up,
      foveoschisis and VA worsened in 20 eyes and remained stable in nine. Ten of the
      20 eyes that worsened had a premacular structure. A macular hole occurred in nine
      eyes, six of which had previously exhibited foveal detachment. Eleven eyes with
      foveoschisis underwent surgery, which improved VA significantly (P = .04,
      Wilcoxon test), but three eyes developed a macular hole. CONCLUSIONS: MF may
      remain stable for many years without affecting VA. However, when it is combined
      with the presence of a premacular structure, the risk of a decrease in VA
      increases. When it is combined with foveal detachment, a macular hole seems to
      develop frequently, whether or not surgery is performed.

PMID- 17222383
TI  - Costs of interventions for visual impairment.
AB  - PURPOSE: To quantify the economic costs of vision loss in Australia and assess
      the impact of a costed intervention package to prevent avoidable vision loss.
      DESIGN: Existing Australian population-based data on prevalence and causes of
      visual impairment were used, and costs were calculated from published data for
      the five main causes of visual impairment. METHODS: The cost of vision loss in
      Australia was determined from the weighted prevalence of visual impairment;
      unpublished data on the indirect costs of vision; and national databases on
      health care costs and other economic data. A costed intervention package was
      developed and its economic impact modeled. Outcome measures were total costs and
      savings from the interventions. RESULTS: The intervention package would cost
      AU$188.8 million to implement in its first year but would bring a net return of
      AU$163.1 million in direct costs in the first year and an overall savings to the
      country of AU$911.1 million, a 4.8-fold return on investment. CONCLUSIONS: Three
      quarters of vision loss is avoidable, and many eye care interventions are cost
      effective. Even a developed economy cannot afford avoidable vision loss. Priority
      needs to be given to the prevention and treatment of avoidable vision loss.

PMID- 17222384
TI  - High-throughput colorimetric method for the parallel assay of glyoxylic acid and
      ammonium in a single extract.

PMID- 17222385
TI  - CYP2E1 active site residues in substrate recognition sequence 5 identified by
      photoaffinity labeling and homology modeling.
AB  - Despite its biological importance, our knowledge of active site structure and
      relevance of critical amino acids in CYP2E1 catalytic processes remain limited.
      In this study, we identified CYP2E1 active site residues using photoaffinity
      labeling with 7-azido-4-methylcoumarin (AzMC) coupled with a CYP2E1 homology
      model. In the absence of light, AzMC was an effective competitor against
      substrate p-nitrophenol oxidation by CYP2E1. Photoactivation of AzMC led to a
      concentration-dependent loss in CYP2E1 activity and structural integrity
      resulting from the modification of both heme and protein. The photo-labeling
      reaction degraded heme and produced a possible heme adduct. Probe incorporation
      into the protein occurred at multiple sites within substrate recognition sequence
      5 (SRS-5). Based on a CYP2E1 homology model, we hypothesize AzMC labels SRS-5
      residues, Leu363, Val364, and Leu368, in the active site. In addition, we propose
      a series of phenylalanines, especially Phe106, mediate contacts with the
      coumarin.

PMID- 17222386
TI  - Increase in fluidity in the membrane of MT3 breast cancer cells correlates with
      enhanced cell adhesion in vitro and increased lung metastasis in NOD/SCID mice.
AB  - To study whether membrane fluidity of tumor cells have an influence on
      metastasis, MT3 breast cancer cells harvested during exponential growth and under
      confluent conditions were compared. Electron paramagnetic resonance (EPR) data
      revealed that, in comparison to growing cells, confluent cells have a significant
      higher fluidity in their membrane related to a higher relative portion of
      disordered domains and a reduced portion of the most ordered domains. Further,
      sialyl Lewis X and/or A ligand-mediated adhesion of these cells was 2-fold
      enhanced. Confocal laser scanning microscopy further demonstrated a higher
      motility of ligands in the membrane of confluent cells, together with an
      accumulation of these ligands in distinct areas. Both facts are suggested to be
      responsible for an enhanced cell adhesion observed. Finally, an increased number
      of large distinct metastatic foci was registered in lungs of mice after i.v.
      inoculation of confluent cells. The results indicate that domain organization and
      fluidity of the cell membrane affect tumor cell adhesion and can have in this way
      also an impact on the malignancy of breast cancer cells.

PMID- 17222387
TI  - Apolipoprotein C-II promoter T-->A substitution at position -190 affects on the
      transcription of the gene and its relationship to hyperlipemia.
AB  - A Chinese patient with severe hypertriglyceridemia was found to have similar
      clinical features to that of malignant hyperlipemia in infancy. DNA sequence
      analysis of the apoC-II gene from the patient's parents revealed a novel
      heterozygous mutation of T-->A substitution at position -190 base in the apoC-II
      promoter. We speculated that the patient was a homozygote of the same mutation
      that resulted in the deficiency of apoC-II. In vitro expression studies showed T-
      >A substitution in the apoC-II promoter leads to a decrease by approximately 20%
      in transcriptional activity compared with its counterpart that inserted the
      normal promoter. These results suggested that T-->A substitution at position -190
      in the apoC-II gene promoter only partly affected transcriptional activity of the
      apoC-II promoter, leading to decrease of apoC-II expression in quantity.

PMID- 17222388
TI  - Glucose- and time-dependence of islet amyloid formation in vitro.
AB  - Islet amyloid contributes to the loss of beta-cell mass in type 2 diabetes. To
      examine the roles of glucose and time on amyloid formation, we developed a rapid
      in vitro model using isolated islets from human islet amyloid polypeptide (hIAPP)
      transgenic mice. Islets from hIAPP transgenic and non-transgenic mice were
      cultured for up to 7 days with either 5.5, 11.1, 16.7 or 33.3mmol/l glucose. At
      various time-points throughout the culture period, islets were harvested for
      determination of amyloid and beta-cell areas, and for measures of cell viability,
      insulin content, and secretion. Following culture of hIAPP transgenic islets in
      16.7 or 33.3mmol/l glucose, amyloid formation was significantly increased
      compared to 5.5 or 11.1mmol/l glucose culture. Amyloid was detected as early as
      day 2 and increased in a time-dependent manner so that by day 7, a decrease in
      the proportion of beta-cell area in hIAPP transgenic islets was evident. When
      compared to non-transgenic islets after 7-day culture in 16.7mmol/l glucose,
      hIAPP transgenic islets were 24% less viable, had decreased beta-cell area and
      insulin content, but displayed no change in insulin secretion. Thus, we have
      developed a rapid in vitro model of light microscopy-visible islet amyloid
      formation that is both glucose- and time-dependent. Formation of amyloid in this
      model is associated with reduced cell viability and beta-cell loss but adequate
      functional adaptation. It thus enables studies investigating the mechanism(s)
      underlying the amyloid-associated loss of beta-cell mass in type 2 diabetes.

PMID- 17222389
TI  - Phosphodiesterase 4 inhibitor regulates the TRANCE/OPG ratio via COX-2 expression
      in a manner similar to PTH in osteoblasts.
AB  - Phosphodiesterase 4 (PDE4) inhibitors stimulate osteoclast formation by
      increasing the TRANCE/OPG mRNA ratio via cAMP-mediated pathways in a manner
      similar to parathyroid hormone (PTH) in osteoblasts. We investigated the role of
      cyclooxygenase-2 (COX-2) in osteoclast formation induced by the PDE4 inhibitor
      rolipram. Rolipram induced COX-2 expression in mRNA and protein levels, followed
      by increased prostaglandin E(2) production in osteoblasts. PKA, ERK, and p38 MAPK
      pathways regulate COX-2 mRNA expression induced by rolipram, in which PKA is a
      central regulator of the ERK and p38 MAPK pathways. A COX-2 inhibitor reversed
      the up-regulation of the TRANCE/OPG mRNA ratio induced by rolipram in
      osteoblasts, resulting in decreased osteoclast formation. These data suggest that
      COX-2 mediates rolipram induced osteoclast formation by regulating the TRANCE/OPG
      mRNA ratio in osteoblasts. Furthermore, the effects of the PDE4 inhibitor on
      osteoblasts were very similar to those of PTH, indicating that the PDE4 inhibitor
      largely shares the biological actions of PTH in osteoblasts.

PMID- 17222391
TI  - Chl1 and Ctf4 are required for damage-induced recombinations.
AB  - Deletion mutants of CHL1 or CTF4, which are required for sister chromatid
      cohesion, showed higher sensitivity to the DNA damaging agents methyl
      methanesulfonate (MMS), hydroxyurea (HU), phleomycin, and camptothecin, similar
      to the phenotype of mutants of RAD52, which is essential for recombination
      repair. The levels of Chl1 and Ctf4 associated with chromatin increased
      considerably after exposure of the cells to MMS and phleomycin. Although the
      activation of DNA damage checkpoint did not affected in chl1 and ctf4 mutants,
      the repair of damaged chromosome was inefficient, suggesting that Chl1 and Ctf4
      act in DNA repair. In addition, MMS-induced sister chromatid recombination in
      haploid cells, and, more importantly, MMS-induced recombination between
      homologous chromosomes in diploid cells were impaired in these mutants. Our
      results suggest that Chl1 and Ctf4 are directly involved in homologous
      recombination repair rather than acting indirectly via the establishment of
      sister chromatid cohesion.

PMID- 17222390
TI  - The l-isoform but not d-isoforms of a JNK inhibitory peptide protects pancreatic
      beta-cells.
AB  - The activation of c-jun N-terminal kinase (JNK) in pancreatic islets is
      associated with impaired function and viability, and JNK inhibitory peptides
      (JNKIs) are cytoprotective. In particular, l-isoforms of JNKIs were shown to
      improve islets viability, while the d-retroinverso isoform of JNKI (RI-JNKI),
      with a higher therapeutic potential due to longer half-life, has not been
      studied. We compared the cytoprotective properties of L-JNKI and RI-JNKI.
      Treatment of murine islets with L-JNKI resulted in preservation of islet
      equivalents and greater percentage of viable beta-cells in culture. In contrast,
      RI-JNKI was not protective. We found that L-JNKI but not RI-JNKI prevents
      endogenous c-jun phosphorylation in insulinoma cells. Moreover, RI-JNKI induced
      islet cells necrosis and activates the p-38 kinase. In conclusion, L-JNKI
      directly affects beta-cells and ameliorates islet viability and function, while
      RI-JNKI has toxic effects, limiting its biological application to islet cell
      biology.

PMID- 17222392
TI  - Conformational state of human cardiac 5-HT(4(g)) receptors influences the
      functional effects of polyclonal anti-5-HT(4) receptor antibodies.
AB  - The functional effects of the anti-G21V antibody directed against the second
      extracellular loop of human heart 5-HT(4) receptors can differ when the receptors
      are expressed in different cell lines. Here, we extend these studies to show
      variation in the responses of 5-HT(4(g)) receptors to the antibody within the
      same expression system. In a previous report no effect of the anti-G21V
      antibodies had been shown upon 5-HT(4(g)) receptors expressed in CHO cells. Here
      the same antibodies alone or when added before 5-HT had a functional "inverse
      agonist like" effect upon 5-HT(4(g)) receptors expressed in a separate line of
      CHO cells. Although these CHO cells showed a lower efficacy of cAMP production
      evoked by 5-HT than the previous report they express a similar h5-HT(4(g))
      receptor density. Inhibition of either phosphodiesterases or Gi proteins had no
      effect upon the action of the antibody. Conformational states of the 5-HT(4)
      receptor and/or equilibrium between different states of receptors may then
      determine the functional effect of antibodies against this receptor.

PMID- 17222393
TI  - Production of extracellular superoxide by human lymphoblast cell lines:
      comparison of electron spin resonance techniques and cytochrome C reduction
      assay.
AB  - Superoxide production by NADPH oxidases plays an important role in the
      development and progression of cardiovascular disease (CVD). However, measurement
      of superoxide (O(2)(-)), a marker of oxidative stress, remains a challenging task
      in clinical and translational studies. In this study we analyzed O(2)(-)
      production in cultured human lymphoblast cell lines by three different methods:
      (a) superoxide dismutase (SOD)-inhibitable cytochrome C reduction, (b) spin
      trapping of superoxide with 5-(ethoxycarbonyl)-5-methyl-1-pyrroline N-oxide
      (EMPO) and 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO), and (c)
      using electron spin resonance (ESR) with the cell-permeable spin probe 1-hydroxy
      3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH). Lymphocytes were isolated
      and immortalized by an Epstein-Barr Virus (EBV)-transformation procedure.
      Superoxide was measured in cultured lymphoblast cell lines at baseline and upon
      stimulation with phorbol 12-myristate 13-acetate (PMA). Cytochrome C and the spin
      traps EMPO and DEPMPO detected two to five times less superoxide compared to CMH.
      Thus, CMH provided the most quantitative measurement of superoxide generation in
      human lymphoblast cell lines. Superoxide detection with CMH was linear dependent
      on cell concentration and was inhibited by SOD but not by catalase. Both cell
      permeable polyethylene glycol (PEG)-SOD and extracellular Cu,Zn-SOD inhibited
      O(2)(-) detection by 90% in PMA-stimulated cells, suggesting a predominantly
      extracellular O(2)(-) generation in human lymphoblasts. Our study describes a new
      technique for O(2)(-) measurement in cultured human lymphoblasts using ESR and
      CMH. A highly sensitive in vitro measurement of O(2)(-) in human cell lines would
      allow investigators to study genotype/phenotype interactions in translational
      studies.

PMID- 17222394
TI  - Abnormal involuntary movements (AIMs) following pulsatile dopaminergic
      stimulation: severe deterioration and morphological correlates following the loss
      of locus coeruleus neurons.
AB  - Parkinsonian patients are treated with dopamine replacement therapy (typically,
      intermittent administration of the dopamine precursor L-DOPA); however, this is
      associated with the onset of abnormal involuntary movements, which seriously
      impair the quality of life. The molecular mechanisms underlying abnormal
      involuntary movements represent an intense field of investigation in the area of
      neurobiology of disease, although their aetiology remains unclear. Apart from the
      fine cellular mechanisms, the pathways responsible for the generation of abnormal
      involuntary movements may involve changes in neurotransmitter systems. A
      potential candidate is noradrenaline, since a severe loss of this
      neurotransmitter characterizes Parkinson's disease, and noradrenergic drugs
      produce a symptomatic relief of L-DOPA-induced dyskinesia. In previous studies we
      found that pulsatile dopamine release, in the absence of the physiological
      noradrenaline innervation, produces motor alterations and ultrastructural changes
      within striatal neurons. In the present study we demonstrate that a unilateral
      damage to the noradrenaline system anticipates the onset and worsens the severity
      of L-DOPA-induced contralateral abnormal involuntary movements in hemi
      parkinsonian rats. Similarly, ubiquitin-positive striatal ultrastructural changes
      occur in unilaterally dopamine-depleted, noradrenaline-deficient rats following
      chronic L-DOPA administration. This study confirms a significant impact of the
      noradrenergic system in the natural history of Parkinson's disease and extends
      its role to the behavioural and morphological effects taking place during
      pulsatile dopamine replacement therapy.

PMID- 17222395
TI  - The O-chain structure from the LPS of the bacterium Naxibacter alkalitolerans YIM
      31775T.
AB  - The O-chain polysaccharide of the lipopolysaccharide from the bacterium
      Naxibacter alkalitolerans strain YIM 31775(T) was characterized. The structure
      was studied by means of chemical analysis and 2D NMR spectroscopy and shown to be
      built up by the following tetrasaccharide repeating unit: -->3)-alpha-D-FucpNAc
      (1-->2)-beta-D-Quip3NHBu-(1-->2)-alpha-D-Rhap-(1-->)-beta-D-Galp-(1--> where HBu
      is hydroxy-butanoyl.

PMID- 17222396
TI  - Serum carboxypeptidase A activity as a biomarker for early-stage pancreatic
      carcinoma.
AB  - BACKGROUND: The early stage of pancreatic carcinoma lacks typical clinical signs
      and symptoms, and is difficult to diagnose. We developed an assay for active form
      of serum carboxypeptidase A (F-CPA) and its zymogen precursor pro CPA, and
      evaluated them as a marker for early-stage pancreatic carcinoma. METHODS: Serum
      CPA from 406 patients including 169 with pancreatic carcinoma, 53 with acute
      pancreatitis, 23 with chronic pancreatitis, and 161 with non-pancreatic diseases
      were assayed by a method with N-acetyl-phenylalanyl-l-3-thiaphenylalanine as
      substrate and dl-benzylsuccinic acid as specific inhibitor of CPA. Activation of
      pro CPA was carried out using trypsin. RESULTS: An established assay system was
      performed fully automatically and possesses enough performance for routine
      clinical assay. This system requires 31 minutes for CPA detection. No significant
      differences were detected between the F-CPA activity of patients with pancreatic
      carcinoma and that of patients with non-pancreatic diseases (p=0.168). F-CPA was
      mainly increased in patients with pancreatitis. Since total-CPA (T-CPA, T-CPA=pro
      CPA+F-CPA) was increased both in patients with pancreatic carcinoma and those
      with acute pancreatitis (p<0.0001, each case), the F-CPA/T-CPA ratio was low only
      in the patients with pancreatic carcinoma. The rate of positivity of T-CPA in the
      early stage of pancreatic carcinoma in which tumor was less than 2 cm was 77%,
      and higher than those of CA19-9 (31%), CEA (8%), and elastase 1 (46%).
      CONCLUSION: It was suggested that assays of both T-CPA and F-CPA in serum might
      be useful for the surveillance of early-stage pancreatic carcinoma.

PMID- 17222398
TI  - Diagnosing scrapie in sheep: a classification experiment.
AB  - Scrapie is a neuro-degenerative disease in small ruminants. A data set of 3113
      records of sheep reported to the Scrapie Notifications Database in Great Britain
      has been studied. Clinical signs were recorded as present/absent in each animal
      by veterinary officials (VO) and a post-mortem diagnosis was made. In an attempt
      to detect healthy animals within the set of suspects using only the clinical
      signs, 18 classification methods were applied ranging from simple linear
      classifiers to classifier ensembles such as Bagging, AdaBoost and Random Forests.
      The results suggest that the clinical classification by the VO was adequate as no
      further differentiation within the set of suspects was feasible.

PMID- 17222397
TI  - Measurement of lysophospholipase D/autotaxin activity in human serum samples.
AB  - OBJECTIVES: Lysophospholipase D (lysoPLD)/autotaxin regulates the blood levels of
      lysophosphatidic acid (LPA), and we designed a serum lysoPLD assay for use in
      clinical laboratory testing. DESIGN AND METHODS: LysoPLD activity was assessed
      based on the amount of choline released with lysophosphatidylcholine as the
      substrate. RESULTS AND CONCLUSIONS: It was confirmed that the lysoPLD assay can
      be applied to clinical laboratory testing. The serum lysoPLD activity in healthy
      female subjects was significantly higher than that in the male subjects.

PMID- 17222399
TI  - Cryo-scanning electron microscopy (Cryo-SEM) of semen frozen in medium-straws
      from good and sub-standard freezer AI-boars.
AB  - A major limiting factor for commercial cryopreservation of boar semen for
      artificial insemination (AI) is the large individual variation to cooling, where
      the degree of cell dehydration during ice (re)shaping seems to play a major role.
      This study investigated, in the frozen state, the degree of dehydration and ice
      crystal distribution in boar semen doses whose spermatozoa displayed different
      viability after thawing. Cross-sectioned medium-straws (0.5 mL, n=10) from a
      total of 10 stud boars classified as "good"(n=5) or sub-standard (e.g., "bad"
      freezers, n=5) by conventional analyses (computer assisted motility and sperm
      viability) were examined by Cryo-scanning electron microscopy (Cryo-SEM) to
      determine whether differences between groups could be already distinguishable
      prior to thawing. The degree of hydration was monitored in relation to the areas
      of ice crystal formed extracellularly (lakes), the areas of frozen, concentrated
      extender (veins) where spermatozoa were located and the degree of
      compartmentalization (number of lakes) present. Irrespectively of the region
      studied, the gradient of main dehydration (as lakes) observed along the cross
      section area of the straws was very irregular. Most spermatozoa were enclosed in
      the freezing extender matrix and no obvious signs of external membrane damage
      were observed. None of the Cryo-SEM variables significantly correlated with post
      thaw sperm parameters (p>0.05). However, we identified significant differences
      (p<0.0001) among boars for all ultrastructure variables studied, including the
      size of the veins, where differences in solute concentration is expected. We
      concluded that despite the large variability in ice crystal formation during the
      conventional freezing process among boars, this is unrelated to inter-boar post
      thaw sperm differences.

PMID- 17222400
TI  - Role of Src family kinases and N-Myc in spermatogonial stem cell proliferation.
AB  - Spermatogonial stem cells are required for the initiation of spermatogenesis and
      the continuous production of sperm. In addition, they can acquire pluripotency
      and differentiate into derivatives of the three embryonic germ layers when
      cultured in the appropriate conditions. Therefore, understanding the signaling
      pathways that lead to self-renewal or differentiation of these cells is of
      paramount importance for the treatment of infertility, the development of male
      contraceptives, the treatment of testicular cancers, and ultimately for tissue
      regeneration. In this report, we studied some of the signaling pathways triggered
      by glial cell line-derived neurotrophic factor (GDNF), a component of the
      spermatogonial stem cell niche produced by the somatic Sertoli cells. As model
      systems, we used primary cultures of mouse spermatogonial stem cells, a mouse
      spermatogonial stem cell line and freshly isolated testicular tubules. We report
      here that GDNF promotes spermatogonial stem cell proliferation through activation
      of members of the Src kinase family, and that these kinases exert their action
      through a PI3K/Akt-dependent pathway to up-regulate N-myc expression. Thus, to
      proliferate, spermatogonial stem cells activate mechanisms that are similar to
      the processes observed in brain stem cells and lung progenitors.

PMID- 17222401
TI  - Activity-dependent neuroprotective protein (ADNP) differentially interacts with
      chromatin to regulate genes essential for embryogenesis.
AB  - Complete deficiency in activity-dependent neuroprotective protein (ADNP) results
      in neural tube closure defects and death at days 8.5-9.5 of gestation in the
      mouse (E8.5-9.5). To elucidate ADNP associated pathways, Affymetrix 22,690
      oligonucleotide-based microarrays were used on ADNP knockout and control mouse
      embryos (E9) separated completely from extra embryonic tissue. Marked differences
      in expression profiles between ADNP-deficient embryos and ADNP-expressing embryos
      were discovered. Specifically, a group of dramatically up-regulated gene
      transcripts in the ADNP-deficient embryos were clustered into a family encoding
      for proteins enriched in the visceral endoderm such as apolipoproteins,
      cathepsins and methallotionins. In contrast, a down regulated gene cluster
      associated with ADNP-deficiency in the developing embryo consisted of
      organogenesis markers including neurogenesis (Ngfr, neurogenin1, neurod1) and
      heart development (Myl2). The pluripotent P19 cells were used for ADNP-chromatin
      immunoprecipitation, showing direct interactions with multiple relevant gene
      promoters including members of the up-regulated as well as the down-regulated
      gene clusters. A comparison between non-differentiated and neuro-differentiated
      P19 cells revealed increased chromatin interaction of ADNP with chromatin from
      differentiated cells. These results place ADNP at a crucial point of gene
      regulation, repressing potential endoderm genes and enhancing genes associated
      with organogenesis/neurogenesis.

PMID- 17222402
TI  - Target of rapamycin (TOR) signaling controls epithelial morphogenesis in the
      vertebrate intestine.
AB  - The target of rapamycin (TOR) signaling pathway regulates cell growth and
      proliferation, however the extent to which TOR signaling mediates particular
      organogenesis programs remains to be determined. Here we report an examination of
      TOR signaling during zebrafish development, using a combination of small molecule
      treatment and morpholino-mediated gene knockdown. First, we amplified and
      sequenced the full-length cDNA for the zebrafish TOR ortholog (ztor). By in situ
      hybridization, we found that ztor is expressed ubiquitously in the early embryo,
      but displays a dynamic pattern in the gut between 48 and 72 h post-fertilization
      (hpf). Treatment of zebrafish embryos with rapamycin induced only a mild general
      developmental delay up to 72 hpf, but digestive tract development became arrested
      at the primitive gut tube stage. Rapamycin inhibited intestinal epithelial
      growth, morphogenesis and differentiation. Using morpholino-mediated gene
      knockdown of TOR pathway components, we show that this effect is mediated
      specifically by the rapamycin-sensitive TOR complex 1 (TORC1). Thus, in addition
      to regulating cell growth and proliferation, TOR signaling controls the
      developmental program guiding epithelial morphogenesis in the vertebrate
      intestine.

PMID- 17222403
TI  - Runx3 regulates dendritic epidermal T cell development.
AB  - The Runx3 transcription factor regulates development of T cells during
      thymopoiesis and TrkC sensory neurons during dorsal root ganglia neurogenesis. It
      also mediates transforming growth factor-beta signaling in dendritic cells and is
      essential for development of skin Langerhans cells. Here, we report that Runx3 is
      involved in the development of skin dendritic epidermal T cells (DETCs); an
      important component of tissue immunoregulation. In developing DETCs, Runx3
      regulates expression of the alphaEbeta7 integrin CD103, known to affect migration
      and epithelial retention of DETCs. It also regulates expression of IL-2 receptor
      beta (IL-2Rbeta) that mediates cell proliferation in response to IL-2 or IL-15.
      In the absence of Runx3, the reduction in CD103 and IL-2Rbeta expression on
      Runx3(-/-) DETC precursors resulted in impaired cell proliferation and
      maturation, leading to complete lack of skin DETCs in Runx3(-/-) mice. The data
      demonstrate the requirement of Runx3 for DETCs development and underscore the
      importance of CD103 and IL-2Rbeta in this process. Of note, while Runx3(-/-) mice
      lack both DETCs and Langerhans cells, the two most important components of skin
      immune surveillance, the mice did not develop skin lesions under pathogen-free
      (SPF) conditions.

PMID- 17222404
TI  - Parity-induced mammary epithelial cells are multipotent and express cell surface
      markers associated with stem cells.
AB  - Parity-induced mammary epithelial cells (PI-MECs) are defined as a pregnancy
      hormone-responsive cell population that activates the promoter of late milk
      protein genes during the second half of pregnancy and lactation. However, unlike
      their terminally differentiated counterparts, these cells do not undergo
      programmed cell death during post-lactational remodeling of the gland. We
      previously demonstrated that upon transplantation into an epithelial-free mammary
      fat pad, PI-MECs exhibited two important features of multipotent mammary
      epithelial progenitors: a) self-renewal, and b) contribution to ductal and
      alveolar morphogenesis. In this new report, we introduce a new method to viably
      label PI-MECs. Using this methodology, we analyzed the requirement of ovarian
      hormones for the maintenance of this epithelial subtype in the involuted mammary
      gland. Furthermore, we examined the expression of putative stem cell markers and
      found that a portion of GFP-labeled PI-MECs were part of the CD24(+)/CD49f(high)
      mammary epithelial subtype, which has recently been suggested to contain
      multipotent stem cells. Subsequently, we demonstrated that isolated PI-MECs were
      able to form mammospheres in culture, and upon transplantation, these purified
      epithelial cells were capable of establishing a fully functional mammary gland.
      These observations suggest that PI-MECs contain multipotent progenitors that are
      able to self renew and generate diverse epithelial lineages present in the murine
      mammary gland.

PMID- 17222405
TI  - Comparison of the effects of mGluR1 and mGluR5 antagonists on the expression of
      behavioral sensitization to the locomotor effect of morphine and the morphine
      withdrawal jumping in mice.
AB  - The aim of the present study was to compare the influence of group I metabotropic
      glutamate receptor (mGluR) antagonists (mGluR1 and mGluR5) on the expression of
      sensitization to the locomotor effect of morphine. We also tested how these
      compounds affect the morphine withdrawal jumps in mice. In our study, the mGluR1
      antagonist EMQMCM [3-ethyl-2-methyl-quinolin-6-yl-(4-methoxy-cyclohexyl)
      methanone methanesulfonate] and the mGluR5 antagonist MTEP ([(2-methyl-1,3
      thiazol-4-yl) ethynyl] pyridine) were used. Sensitization was induced by five
      intraperitoneal (i.p.) injections of morphine at the dose of 10 mg/kg, every 3
      days. Morphine dependence was induced by subcutaneous (s.c.) implantation of
      pellets containing 37.5 mg of morphine base for three days. Our data indicate
      that pretreatment with EMQMCM (5, 10, 20 mg/kg) and MTEP (5, 10 mg/kg) on the
      challenge day, inhibited the expression of sensitization to the locomotor effect
      of morphine in mice. Antagonists of both subtypes of the group I mGlurs given
      alone, did not modify the acute locomotor effect of morphine. On the other hand,
      EMQMCM did not attenuate the morphine withdrawal jumps precipitated by naloxone
      (4 mg/kg). The results suggest that both subtypes of the group I mGluRs (mGluR1
      and mGluR5) take part in the expression of morphine sensitization processes but
      mGluR1 is not involved in the expression of morphine withdrawal jumps in mice.
      These findings may have implications for the treatment of opiate addiction in
      future.

PMID- 17222406
TI  - Intravenous heparin in combination with antibiotics for the treatment of deep
      vein septic thrombophlebitis: a systematic review.
AB  - Antibiotics, heparin, and several surgical interventions have been used in
      various combinations for the treatment of septic thrombophlebitis, but the
      optimal management remains unclear. There are limited data from comparative
      trials studying this issue. Specifically, only one randomized controlled trial
      was conducted, while the rest of the evidence comes from case series and case
      reports. The results of this systematic review of septic thrombophlebitis suggest
      that the use of heparin in combination with antibiotics is associated with low
      mortality in patients with this serious type of infection. In addition, adverse
      effects related to heparin were limited in the reported literature. Although data
      from comparative trials are required to draw definitive conclusions, the
      available evidence suggests that the administration of heparin should be
      considered early in the management of patients with septic thrombophlebitis.

PMID- 17222407
TI  - Increase of cannabinoid CB1 receptor density in the hippocampus of streptozotocin
      induced diabetic rats.
AB  - In the hippocampus, impaired neurophysiology, compromised neurogenesis, and
      eventually apoptosis accompany cognitive deficits in insulinopenic (type-1)
      diabetes (T1D). The underlying pathological mechanisms remain to be defined. The
      hippocampus has a high density of the cannabinoid type 1 receptor (CB(1)R), which
      has been shown to control several brain functions affected by diabetes, such as
      synaptic plasticity, glucose utilisation, memory consolidation and cognition, and
      maturation and survival of hippocampal neurons. However, the role of this
      receptor has not been investigated yet in diabetic encephalopathy. We report now
      that in the streptozotocin animal model of T1D, the hippocampal densities of
      CB(1)R protein and of specific CB(1)R binding sites are significantly increased
      both in the nerve terminals and in total membranes (changes between 13% and 38%),
      whereas CB(1)R mRNA expression is decreased by 25%, suggesting that CB(1)Rs might
      play a role in diabetic encephalopathy.

PMID- 17222408
TI  - Extensive unfolding of the C-LytA choline-binding module by submicellar
      concentrations of sodium dodecyl sulphate.
AB  - We have investigated the stability of the choline-binding module C-LytA against
      sodium dodecyl sulphate (SDS)-induced unfolding at pH 7.0 and 20 degrees C. A
      major intermediate with an unfolded N-terminal region accumulates at around 0.75
      mM SDS, whereas 2.0 mM SDS was sufficient for a complete unfolding. This might be
      the first report of a protein being extensively unfolded by submicellar
      concentrations of SDS, occurring through formation of detergent clusters on the
      protein surface. All transitions were reversible upon SDS complexation with beta
      cyclodextrin, allowing the calculation of thermodynamic parameters. A model for
      the unfolding of C-LytA by SDS is presented and compared to a previous
      denaturation scheme by guanidine hydrochloride.

PMID- 17222409
TI  - Photometrical analysis with photosensory domains of photoreceptors in green
      algae.
AB  - Chloroplast photoorientation in the green alga Mougeotia scalaris is controlled
      by blue and red light. The properties of the LOV domains of phototropin A and B
      were consistent with previous data of action spectra and photoreceptor lifetime
      for blue light-mediated photoorientation. The LOV domains of the neochromes did
      not bind flavin, while the domains of neochrome 2 contributed to multimer
      formation. The absorption spectra of the neochrome phytochrome photosensory
      domain with phytochromobilin were very similar to the action spectra for red
      light-induced photoorientation. These results indicate that phototropin and
      neochrome work as the blue and red photoreceptors involved in photoorientation.

PMID- 17222410
TI  - A Turnip yellow mosaic virus infection system in Arabidopsis suspension cell
      culture.
AB  - Turnip yellow mosaic virus (TYMV) is a positive-strand RNA virus able to infect
      Arabidopsis thaliana. To establish a TYMV infection system in Arabidopsis cell
      culture, TYMV replicons with the capsid protein gene replaced by a reporter gene
      expressing the Sh ble protein conferring zeocin resistance were used to transfect
      Arabidopsis cells. Zeocin-resistant Arabidopsis calli were used to generate a
      suspension cell culture. Detection of viral proteins and RNAs after 18 months in
      culture demonstrated persistent replication of the replicon. The Arabidopsis cell
      culture yielded soluble, active replication complexes, providing a useful tool to
      study host factors involved in TYMV replication.

PMID- 17222411
TI  - Functional glycosylation of human podoplanin: glycan structure of platelet
      aggregation-inducing factor.
AB  - Podoplanin (Aggrus) is a mucin-type sialoglycoprotein that plays a key role in
      tumor cell-induced platelet aggregation. Podoplanin possesses a platelet
      aggregation-stimulating (PLAG) domain, and Thr52 in the PLAG domain of human
      podoplanin is important for its activity. Endogenous or recombinant human
      podoplanin were purified, and total glycosylation profiles were surveyed by
      lectin microarray. Analyses of glycopeptides produced by Edman degradation and
      mass spectrometry revealed that the disialyl-corel (NeuAc alpha2-3Gal beta l
      3(NeuAc alpha2-6)GalNAc alpha l-O-Thr) structure was primarily attached to a
      glycosylation site at residue Thr52. Sialic acid-deficient podoplanin recovered
      its activity after additional sialylation. These results indicated that the
      sialylated Corel at Thr52 is critical for podoplanin-induced platelet
      aggregation.

PMID- 17222412
TI  - Involvement of phosphatidylinositol-3-kinase and ERK pathways in the production
      of TGF-beta1 by macrophages treated with liposomes composed of
      phosphatidylserine.
AB  - We explored the involvement of phosphatidylinositol 3-kinase (PI3K) and ERK
      pathways in the production of TGF-beta1 by macrophages treated with liposomes
      composed of phosphatidylserine (PS-liposomes). PS-liposomes activated Akt,
      downstream of the PI3K signal cascade, and ERK which led to the expression of TGF
      beta1. PI3K inhibitors, LY294002 and wortmannin, inhibited the activation of Akt
      and ERK following the treatment with PS-liposomes. These inhibitors also
      suppressed the production of TGF-beta1. Furthermore, PS-liposomes activated
      macrophages to induce TGF-beta1 expression through PS-specific receptors. These
      findings suggested that a PI3K-ERK signaling pathway via the PS-receptor is
      intimately involved in the production of TGF-beta1 which regulates macrophage
      functions.

PMID- 17222413
TI  - The effects of a Simplified Tai-Chi Exercise Program (STEP) on the physical
      health of older adults living in long-term care facilities: a single group design
      with multiple time points.
AB  - BACKGROUND: Studies support the positive effects that Tai Chi has on the physical
      health of older adults. However, many older adults residing in long-term care
      facilities feel too weak to practice traditional Tai Chi, and a more simplified
      style is preferred. OBJECTIVE: To test the effects of a newly-developed,
      Simplified Tai-Chi Exercise Program (STEP) on the physical health of older adults
      who resided in long-term care facilities. DESIGN: A single group design with
      multiple time points: three pre-tests, one month apart; four post-tests at one
      month, two months, three months, and six months after intervention started.
      SETTINGS: Two 300-400 bed veteran homes in Taiwan. PARTICIPANTS: The 51 male
      older adults were recruited through convenience sampling, and 41 of them
      completed six-month study. Inclusion criteria included: (1) aged 65 and over; (2)
      no previous training in Tai Chi; (3) cognitively alert and had a score of at
      least eight on the Short Portable Mental Status Questionnaire; (4) able to walk
      without assistance; and (5) had a Barthel Index score of 61 or higher.
      Participants who had dementia, were wheel-chair bound, or had severe or acute
      cardiovascular, musculoskeletal, or pulmonary illnesses were excluded. METHODS:
      The STEP was implemented three times a week, 50 min per session for six months.
      The outcome measures included cardio-respiratory function, blood pressure,
      balance, hand-grip strength, lower body flexibility, and physical health
      actualization. RESULTS: A drop in systolic blood pressure (p=.017) and diastolic
      blood pressure (p<.001) was detected six months after intervention started.
      Increase in hand-grip strength from pre to post intervention was found (left
      hand: p<.001; right hand: p=.035). Participants also had better lower body
      flexibility after practicing STEP (p=.038). CONCLUSIONS: Findings suggest that
      the STEP be incorporated as a floor activity in long-term care facilities to
      promote physical health of older adults.

PMID- 17222415
TI  - Divergent associations of tissue inhibitors of metalloproteinases-1 and -2 with
      the prothrombotic/fibrinolytic state.

PMID- 17222414
TI  - Social stress profoundly affects lipid metabolism: over-expression of SR-BI in
      liver and changes in lipids and lipases in plasma and tissues of stressed mice.
AB  - We examined the effect of chronic social stress, similar to that endured by
      humans, on lipid metabolism of mice. The activity of the lipoprotein lipase (LPL)
      enzyme increased in adrenals, while in plasma it diminished significantly.
      Hepatic lipase (HL) was strongly affected in liver and adrenal glands, increasing
      four-fold and three-fold, respectively. At the same time, scavenger receptor
      class-B type-I (SR-BI), which are considered the high-density lipoprotein (HDL)
      receptor in the liver, increased significantly. Although the adrenals do not
      synthesise HL, the increase in HL may facilitate the uptake of HDL cholesterol
      for the synthesis of corticoids, which increase significantly following chronic
      stress. The volume of adrenal glands in control animals was significantly higher
      than in stressed animals (1.23+/-0.12 mm3 versus 0.29+/-0.06 mm3, p<0.001),
      corresponding with the weight difference of these organs. Medulla volume was also
      different in the two groups (0.27+/-0.10 mm3 versus 0.04+/-0.02 mm3, p<0.05).
      Despite this, corticosterone in plasma was significantly higher in stressed
      animals. Our results shows, for the first time, the effect of chronic social
      stress on lipid metabolism in general, and in particular on the SR-BI receptor
      and HL, which is directly involved in cholesterol reverse transport.

PMID- 17222416
TI  - Evaluation of chiral ionic liquids as additives to cyclodextrins for enantiomeric
      separations by capillary electrophoresis.
AB  - A great interest has been drawn these last years towards ionic liquids in
      analytical chemistry, especially for separation methods. Recent synthesis of
      chiral ILs opened the way of the evaluation of new potential selectors for
      enantiomeric separations. This work focused on the evaluation of two chiral ILs
      (ethyl- and phenylcholine of bis(trifluoromethylsulfonyl)imide) by CE. Particular
      selectivities are awaited by exploiting unique ion-ion or ion-dipole interactions
      and by tailoring the nature of the cation and the anion. To evaluate such
      phenomena, a study was carried out with anti-inflammatory drugs 2-arylpropionic
      acids as model compounds. The results show that these chiral ILs did not present
      direct enantioselectivity with regard to these model analytes. The influence of
      chiral ILs in the electrolytes was then studied in the presence of classical
      chiral selectors (di- or trimethyl-beta-cyclodextrin). Although no general trend
      could be established, an increase in separation selectivity and resolution was
      observed in some cases, suggesting synergistic effects. The complementary
      determination of apparent inclusion constant values of these IL cations in the
      used cyclodextrins by affinity CE provided support to the understanding of the
      phenomena involved.

PMID- 17222418
TI  - Adsorption of water-soluble polymers with surfactant character. Adsorption
      kinetics and equilibrium properties.
AB  - A comparative study between Langmuir and Gibbs monolayers of a hyperbranched
      polyol, poly(propylene glycol) homopolymers, and poly(propylene glycol)
      poly(ethylene glycol) copolymers with different structure and molecular weight,
      is reported. Dynamic surface tension (DST) and surface pressure measurements have
      been carried out to characterize these amphiphilic water-soluble polymers. The
      adsorption kinetics results are consistent with a rapid diffusion stage followed
      by a slow reorganization at the air-water interface. The characteristic times of
      these steps, calculated by the Joos model, point out differences among the
      polymers in the diffusion rate and rearrangement mechanisms for diluted
      solutions. Short time analysis of DST data leads to diffusion coefficients in
      qualitative agreement with the diffusion times calculated with Joos' model.
      Spread monolayers remain stable for long periods of time. The desorption process
      seems quite inoperative. As a consequence, the surface pressure of the spread
      monolayers can be studied over a broad surface concentration range. 2D first
      order phase transitions have been evidenced from plateaux observed in Langmuir
      and Gibbs isotherms. It has been found that Gibbs monolayers lead to lower
      surface tension states than the Langmuir ones.

PMID- 17222417
TI  - Simultaneous determination of rocuronium and its eight impurities in
      pharmaceutical preparation using high-performance liquid chromatography with
      amperometric detection.
AB  - A sensitive and selective HPLC method with amperometric detection (HPLC-ED) for
      the determination of rocuronium bromide and its eight impurities has been
      developed. The analysis was performed on Hypersil 100 Silica column 5 microm (250
      mm x 4.6 mm; Thermo Electron). The mobile phase consisting of 4.53 g l(-1)
      solution of tetramethylammonium hydroxide adjusted to pH 7.4 with 85% phosphoric
      acid:acetonitrile (1:9), was found the best for the separation and determination
      of the studied compounds. The chromatograms were recorded over 10 min using the
      amperometric detection at a potential +0.9 V of the glassy carbon electrode
      versus the reference electrode Ag/AgCl. The limit of quantitation was 45 ng ml(
      1) for rocuronium and from 25 to 750 ng ml(-1) for the examined impurities. The
      proposed HPLC-ED method was successfully applied to the analysis of rocuronium
      and its impurities in Esmeron solution for injection.

PMID- 17222419
TI  - Structural studies of the phase, aggregation and surface behaviour of 1-alkyl-3
      methylimidazolium halide + water mixtures.
AB  - The surface, phase and aggregation behaviour of mixtures of 1-alkyl-3
      methylimidazolium halide, [C(n)mim]X, where n is the alkyl chain length, with
      water has been explored using a variety of methods. Critical micelle
      concentrations (cmc) and micelle structures have been determined for aqueous
      [C(n)mim]Br solutions for n=2, 4, 6, 8, and 10. Small-angle neutron scattering
      (SANS) measurements reveal that for the n=8 and 10 systems, at concentrations
      just above the cmc, small near-spherical aggregates exist, which, after initial
      growth, possess core radii (aggregation numbers) at intermediate concentrations
      of 10.5+/-0.5 Angstrom (22+/-2) and 13.2+/-0.5 Angstrom (40+/-3), respectively,
      for n=8 and n=10. Towards higher concentrations, the aggregates appear to grow,
      with the aggregates in the [C(10)mim]Br system becoming increasingly elongated
      (prolate) with increasing concentration. No evident aggregates are formed in the
      systems with n=2 and 4. In the n=6 system, it appears that oblate aggregates with
      radius approximately 9 Angstrom form at the cmc and that the radius increases
      with increasing concentration. For longer alkyl chain lengths, at high
      concentrations lyotropic mesophases form in some systems. The mesophase region
      for the [C(8)mim]Cl system has been explored across the composition range using X
      ray diffraction and (2)H NMR spectroscopy. Both techniques suggest that a major
      hexagonal phase with lattice parameter of 29.5+/-0.5 Angstrom coexists with a
      minor lamellar phase (23.5+/-0.3 Angstrom) or possibly a second hexagonal phase
      (27.1+/-0.4 Angstrom). The area per adsorbed molecule at the surface of
      [C(8)mim]Br solutions has been measured as a function of concentration using
      neutron reflectometry. A minimum in the area per molecule behaviour is coincident
      with a minimum identified in the surface tension isotherm occurring close to the
      cmc. The data suggest depletion of [C(8)mim]Br from the surface region occurs at
      concentrations immediately above the cmc.

PMID- 17222420
TI  - Influence of the intercalated cations on the surface energy of montmorillonites:
      consequences for the morphology and gas barrier properties of
      polyethylene/montmorillonites nanocomposites.
AB  - Organically modified montmorillonites obtained by cation exchange from the same
      natural layered silicate were studied. The surface properties of the pristine and
      a series of organically modified clays were determined by inverse gas
      chromatography and the water adsorption mechanisms were studied by a gravimetric
      technique coupled with a microcalorimeter. A significant increase of the specific
      surface area, a decrease of the water adsorption, and a decrease of the
      dispersive component of the surface energy were observed when the sodium cations
      of the natural montmorillonite were exchanged for a quaternary ammonium. Slighter
      differences in surface properties were observed, on the other hand, between the
      different types of organically modified montmorillonites. Indeed, similar
      dispersive components of the surface energy were determined on the organoclays.
      Nevertheless, the specific surface area increased in the range 48-80 m(2)/g with
      increasing d-spacing values and the presence of specific groups attached to the
      quaternary ammonium, such as phenyl rings or hydroxyl groups, led to some
      specific behaviors, i.e., a more pronounced base character and a higher water
      adsorption at high activity, respectively. Differences in interlayer cation chain
      organization, denoted as crystallinity, were also observed as a function of the
      nature of the chains borne by the quaternary ammonium. In a later step,
      polyethylene-based nanocomposites were prepared with those organically modified
      montmorillonites. The clay dispersion and the barrier properties of the
      nanocomposites were discussed as a function of the montmorillonite
      characteristics and of the matrix/montmorillonite interactions expected from
      surface energy characterization.

PMID- 17222421
TI  - Synthesis of stable luminescent microspheres by a simple method.
AB  - An easy procedure for preparing microspheres containing CdSe/CdS core-shell
      quantum dots (QDs) was demonstrated. The luminescent properties of this
      microsphere were characterized by fluorescence microscopy and fluorescence
      spectrophotometry. Scanning electron microscopy was also used in this study.
      Laser confocal microscopy was carried out to describe the distribution of QDs in
      the microsphere. Especially, the stability of microspheres was investigated. It
      was found that the getting microsphere was very stable in water and showed values
      for physiological conditions. The inherent stability of the spheres, as well as
      their photostability, allows them to be used in biological applications.

PMID- 17222422
TI  - A dual color ELISPOT method for the simultaneous detection of IL-2 and IFN-gamma
      HIV-specific immune responses.
AB  - The single color IFN-gamma ELISPOT assay has become a standard for assessing HIV
      specific immune responses in HIV-infected subjects. However, recent data suggests
      that single cytokine detection for immune monitoring of HIV-infected individuals
      may not be sufficient to fully describe virus-specific immune responses. Here, we
      have designed and validated a dual color ELISPOT assay capable of detecting both
      IL-2 and IFN-gamma secreting cells simultaneously in response to HIV antigens. We
      found that a cell input number of 200,000 cells/well provided a good balance
      between limited availability of cells due to blood volume restrictions and
      ability to detect all cytokine secretion patterns. The simultaneous detection of
      IL-2 and IFN-gamma resulted in a decreased magnitude of IFN-gamma but not IL-2
      responses. Measures of intra- and inter-assay variability for the dual color
      ELISPOT assay were comparable to that seen for single cytokine ELISPOT assay with
      coefficients of variation below 20% for IL-2, IFN-gamma and dual secretion.
      Although CD8+ T cells mediated most HIV-specific responses in infected subjects,
      CD4+ T cells mediated responses to HIV were also detected. Features of this assay
      such as high throughput, cell number requirement and cytokine choice should make
      this assay a valuable tool for screening for HIV-specific immune responses in
      several clinically relevant settings.

PMID- 17222423
TI  - Gene therapy for restenosis: biological solution to a biological problem.
AB  - Coronary artery disease remains a significant health threat afflicting millions
      of individuals worldwide. Despite the development of a variety of technologies
      and catheter based interventions, post-procedure restenosis is still a
      significant concern. Gene therapy has emerged as a promising approach aimed at
      modification of cellular processes that give rise to restenosis. When juxtaposed
      alongside the failure of traditional pharmacotherapeutics to eliminate
      restenosis, gene therapy has engendered great expectations for cubing coronary
      restenosis. In this review we have discussed an overview of gene therapy
      approaches that hve been utilized to reduce restenosis in preclinical and
      clinical studies, current status of anti-restenosis gene therapy and perspectives
      on its future application. For brevity, we have limited our discussion on anti
      restenosis gene therapy to the introduction of a nucleic acid to the cell,
      tissue, organ or organism in order to give rise to the expression of a protein,
      the function of which will confer therapeutic effect. For the purpose of this
      review, we have focused ou discussion on two relevant anti-restenosis strategies,
      anti-proliferative and pro-endothelialization.

PMID- 17222424
TI  - NMR and cDNA array analysis prior to heart failure reveals an increase of
      unsaturated lipids, a glutamine/glutamate ratio decrease and a specific
      transcriptome adaptation in obese rat heart.
AB  - Obesity is a risk factor for heart failure through a set of hemodynamic and
      hormonal adaptations, but its contribution at the molecular level is not clearly
      known. Therefore, we investigated the kinetic cardiac transcriptome and
      metabolome in the Spontaneous Hypertensive Heart Failure (SHHF) rat. The SHHF rat
      is devoid of leptin signaling when homozygous for a mutation of the leptin
      receptor (ObR) gene. The ObR-/- SHHF rat is obese at 4 months of age and prone to
      heart failure after 14 months whereas its lean counterpart ObR-/+ is prone to
      heart failure after 16 months. We used a set of rat pangenomic high-density
      macroarrays to monitor left ventricle cardiac transcriptome regulation in 4- and
      10-month-old, lean and obese animals. Comparative analysis of left ventricle of 4
      and 10-month-old lean rat revealed 222 differentially expressed genes while 4-
      and 10-month-old obese rats showed 293 differentially expressed genes. (1)H NMR
      analysis of the metabolome of left ventricular extracts displayed a global
      decrease of metabolites, except for taurine, and lipid concentration. This may be
      attributed to gene expression regulation and likely increased extracellular mass.
      The glutamine to glutamate ratio was significantly lower in the obese group. The
      relative unsaturation of lipids increased in the obese heart; in particular,
      omega-3 lipid concentration was higher in the 10-month-old obese heart. Overall,
      several specific kinetic molecular patterns act as a prelude to heart failure in
      the leptin signaling deficient SHHF obese rat.

PMID- 17222425
TI  - Structure of thiocyanate hydrolase: a new nitrile hydratase family protein with a
      novel five-coordinate cobalt(III) center.
AB  - Thiocyanate hydrolase (SCNase) of Thiobacillus thioparus THI115 is a cobalt(III)
      containing enzyme catalyzing the degradation of thiocyanate to carbonyl sulfide
      and ammonia. We determined the crystal structures of the apo- and native SCNases
      at a resolution of 2.0 A. SCNases in both forms had a conserved hetero
      dodecameric structure, (alphabetagamma)(4). Four alphabetagamma hetero-trimers
      were structurally equivalent. One alphabetagamma hetero-trimer was composed of
      the core domain and the betaN domain, which was located at the center of the
      molecule and linked the hetero-trimers with novel quaternary interfaces. In both
      the apo- and native SCNases, the core domain was structurally conserved between
      those of iron and cobalt-types of nitrile hydratase (NHase). Native SCNase
      possessed the post-translationally modified cysteine ligands, gammaCys131-SO(2)H
      and gammaCys133-SOH like NHases. However, the low-spin cobalt(III) was found to
      be in the distorted square-pyramidal geometry, which had not been reported before
      in any protein. The size as well as the electrostatic properties of the substrate
      binding pocket was totally different from NHases with respect to the charge
      distribution and the substrate accessibility, which rationally explains the
      differences in the substrate preference between SCNase and NHase.

PMID- 17222426
TI  - Crystal structure of the N-terminal domain of the TyrR transcription factor
      responsible for gene regulation of aromatic amino acid biosynthesis and transport
      in Escherichia coli K12.
AB  - The X-ray structure of the N-terminal domain of TyrR has been solved to a
      resolution of 2.3 A. It reveals a modular protein containing an ACT domain, a
      connecting helix, a PAS domain and a C-terminal helix. Two dimers are present in
      the asymmetric unit with one monomer of each pair exhibiting a large rigid-body
      movement that results in a hinging around residue 74 of approximately 50 degrees
      . The structure of the dimer is discussed with reference to other transcription
      regulator proteins. Putative binding sites are identified for the aromatic amino
      acid cofactors.

PMID- 17222427
TI  - Mutational analyses define helix organization and key residues of a bacterial
      membrane energy-transducing complex.
AB  - In Gram-negative bacteria, many biological processes are coupled to inner
      membrane ion gradients. Ions transit at the interface of helices of integral
      membrane proteins, generating mechanical energy to drive energetic processes. To
      better understand how ions transit through these channels, we used a model system
      involved in two different processes, one of which depends on inner membrane
      energy. The Tol machinery of the Escherichia coli cell envelope is dedicated to
      maintaining outer membrane stability, a process driven by the proton-motive
      force. The Tol system is parasitized by bacterial toxins called colicins, which
      are imported through the outer membrane using an energy-independent process.
      Herein, we mutated TolQ and TolR transmembrane residues, and we analyzed the
      mutants for outer membrane stability, colicin import and protein complex
      formation. We identified residues involved in the assembly of the complex, and a
      new class of discriminative mutations that conferred outer membrane
      destabilization identical to a tol deletion mutant, but which remained fully
      sensitive to colicins. Further genetic approaches revealed transmembrane helix
      interactions and organization in the bilayer, and suggested that most of the
      discriminative residues are located in a putative aqueous ion channel. We discuss
      a model for the function of related bacterial molecular motors.

PMID- 17222428
TI  - Elevated plasma arginine vasopressin levels in veterans with posttraumatic stress
      disorder.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with altered
      hypothalamic-pituitary-adrenal (HPA) axis functioning. Arginine vasopressin
      (AVP), in conjunction with corticotrophin releasing hormone, has shown to be an
      important modulator of the HPA axis. In order to evaluate the effect of trauma
      and PTSD on central AVP secretion we assessed plasma AVP levels in equally trauma
      exposed veterans with and without PTSD and a non-traumatized healthy control
      group. METHODS: Assessment of plasma AVP in 29 male veterans with PTSD, 29
      traumatized veterans without PTSD, matched for age, gender, year and region of
      deployment (trauma controls), and 26 age matched healthy controls. RESULTS:
      Plasma AVP levels were higher in PTSD patients compared to both healthy controls
      (p = 0.004) and trauma controls (p < 0.001). In PTSD patients without a comorbid
      MDD a significant correlation was observed between plasma AVP levels and symptoms
      of avoidance measured with the Clinician Administered PTSD Scale (CAPS).
      CONCLUSION: Elevated plasma AVP levels are specifically related to PTSD and not
      to exposure to traumatic stress during deployment. Our results indicate that AVP
      may play a role as an anxiogenic factor, but they do not support a role for AVP
      in the altered response to dexamethasone in PTSD.

PMID- 17222429
TI  - Mediation of burn-induced hypermetabolism by CRF receptor-2 activity.
AB  - Hypermetabolism and anorexia are significant problems associated with major burn
      trauma. Recent studies have implicated hypothalamic peptides and receptors of the
      corticotropin releasing factor (CRF) family as putative mediators of burn-induced
      hypermetabolism. Increased neuronal activity at the CRF type 2 receptor (CRF R-2)
      appeared particularly involved in the expression of elevated resting energy
      expenditure (REE) following major burn trauma. In the present study we continued
      these investigations of CRF R-2 mediation of burn-induced hypermetabolism,
      demonstrating that 3rd ventricle injection of CRF R-2 antisense
      oligodeoxynucleotide (ODN) normalized REE in burned rats. Similar treatments with
      CRF or CRF R-1 antisense ODNs had no significant effect in burned rats. In
      addition, 3rd ventricle injection of the selective CRF R-2 antagonist,
      antisauvagine-30, also reduced REE significantly in burned rats, while similar
      treatment with the selective CRF R-1 antagonist, antalarmin, was without effect.
      To determine which endogenous peptide was altered following burn we measured
      hypothalamic levels of urocortin (UCN) and CRF 15 days after burn injury, finding
      UCN was significantly elevated by nearly 3-fold, while CRF level tended to be
      decreased. We also assessed hypothalamic mRNA peptide and receptor expression by
      real-time PCR 7, 14, and 21 days post-burn, observing decreased CRF expression 7
      and 21 days post-burn, decreased UCN-2 expression 7 days post-burn, and no
      significant alteration in UCN-1 at any time point. However, CRF R-2 mRNA was
      elevated at each post-burn time point. These results continue to suggest that
      increased neuronal activity is integrally involved in the mediation of burn
      induced hypermetabolism, and that one of the UCN peptides may be the endogenous
      ligand affecting this receptor.

PMID- 17222431
TI  - Biodegradation of petroleum products in experimental plots in Antarctic marine
      sediments is location dependent.
AB  - Clean sediment collected from O'Brien Bay, East Antarctica, was artificially
      contaminated with a mix of Special Antarctic Blend diesel fuel and lubricating
      oil and deployed in two uncontaminated locations (O'Brien and Sparkes Bays) and a
      previously contaminated bay (Brown Bay) to evaluate whether a history of prior
      contamination would influence the biodegradation process. Detailed analysis of
      the hydrocarbon composition in the sediment after 11 weeks revealed different
      patterns of degradation in each bay. Biodegradation indices showed that
      hydrocarbon biodegradation occurred in all three bays but was most extensive in
      Brown Bay. This study shows that even within a relatively small geographical
      area, the longevity of hydrocarbons in Antarctic marine sediments can be
      variable. Our results are consistent with faster natural attenuation of spilt oil
      at sites with previous exposure to oil but further work is needed to confirm
      this. Such information would be useful when evaluating the true risk and
      longevity of oils spills.

PMID- 17222430
TI  - Molecular aspects of adrenal regulation for circadian glucocorticoid synthesis by
      chronic voluntary exercise.
AB  - Chronic voluntary running of mice is known to increase the circadian peak of
      plasma corticosterone without change in the level of adrenocorticotropic hormone
      (ACTH). In order to investigate how chronic exercise modulates the circadian HPA
      axis, we used two weeks of voluntary wheel running of mice and confirmed the
      significant increase of the circadian peak of plasma corticosterone without
      alteration in ACTH level. To elucidate the mechanisms of exercise modulation on
      corticosterone synthesis, we first examined the levels of transcripts involved in
      corticosterone synthesis of the adrenal gland. Among them, only steroidogenic
      acute regulatory protein (StAR), the rate-limiting factor that transfers
      substrate cholesterol into inner mitochondrial membrane, showed significantly
      higher expression in the exercise group. Since the splanchnic nerve input to the
      adrenal gland has been reported as a factor involved in the direct modulation of
      corticosterone synthesis, we next examined the expression levels of enzymes for
      the catecholamine synthesis as indices of sympatho-adrenomedullary activity. We
      found that the only rate-limiting enzyme, tyrosine hydroxylase (TH), was
      significantly higher in the adrenals of exercise group. In addition to the
      increment of StAR and TH mRNA in response to the chronic exercise, surprisingly,
      we found only these factors showed the circadian variation in its expression
      levels that was correlated to the circadian rhythm of corticosterone. Chronic
      exercise seems to alter the circadian corticosterone synthesis, at least
      partially via altering the levels of circadian-regulated transcripts, StAR and TH
      of the adrenal gland.

PMID- 17222432
TI  - Mercury contamination in invertebrate biota in a temperate coastal lagoon (Ria de
      Aveiro, Portugal).

PMID- 17222433
TI  - Disruption of synaesthesia following TMS of the right posterior parietal cortex.
AB  - This study examines the role of four regions of the parietal lobe in grapheme
      colour synaesthesia. TMS applied over a right parieto-occipital region disrupts
      performance on a synaesthetic priming task. TMS over the left parietal or a more
      anterior right parietal site did not have a reliable effect on synaesthesia even
      though one of the sites had been implicated in synaesthesia by previous fMRI
      studies. The same disruption is found for synaesthetes who experience colours in
      their "mind's eye" as well as those who project colours onto the inducing
      grapheme. This region may be important for binding graphemes and colours to
      different spatial reference frames.

PMID- 17222434
TI  - Tryptophan increases nocturnal rest and affects melatonin and serotonin serum
      levels in old ringdove.
AB  - The sleep promoting functions of melatonin have gained wide scientific attention
      due to the ability of this indole to provide relief from sleep inefficiency and
      the temporal relationship between its nocturnal rise in the blood and the
      "opening of the sleep gate" at night. However, little is known about the effects
      exerted by its precursor, the amino acid tryptophan. We studied the effect of a 7
      day administration of two concentrations of tryptophan (125 and 300 kg b.w.) on
      the activity/rest rhythms of ringdove, aged 2-3 (young) and 10-12 (old) years,
      and on the serum levels of serotonin and melatonin. Activity pulses were logged
      before, during, and up to 5 days after the treatments. The animals received 125
      or 300 mg/kg b.w. per animal/day at 09:00 h or at 19:00 h. Subsequently we chose
      the treatment which gave the best results in terms of nocturnal rest without
      affecting diurnal activity, i.e., 300 mg/kg b.w. administered to old animals at
      09:00 h, 1 h after lights on, for the serotonin and melatonin measurements.
      During this treatment, the nocturnal and diurnal levels and amplitudes of
      serotonin and melatonin were all significantly higher than the corresponding
      levels before and after the treatment. In sum, our results point to an
      improvement of nocturnal rest in this animal model of old ringdove when
      administering 300 mg/kg tryptophan 1 h after lights on.

PMID- 17222436
TI  - Functional epitopes on porcine endogenous retrovirus envelope protein interacting
      with neutralizing antibody combining sites.
AB  - Porcine cell and organ transplantation provides promise for maintaining normal
      physiological conditions in patients with end-stage organ failure. The approach
      however poses serious risk of transmitting pig pathogens to humans. Among many
      potential pathogens, porcine endogenous retroviruses (PERV) are of particular
      concern due to their ubiquitous nature in pigs and capability of infecting human
      cells. Major antigenic determinants and receptor binding domains on PERV remain
      unclear until now. Two monoclonal antibodies (mAb), named 8E10 and 7C4 capable of
      neutralizing PERV infection in HEK293 cells are isolated at an IC(50) of 3.0 and
      2.7 microg/ml, respectively, in this work. Epitope location for mAb 8E10 was
      mapped to amino acids 427-434, residing at the C-terminal region of the gp70
      component of type A PERV Env protein. The mAb 8E10 bound directly to the PERV
      indicating that the epitope is exposed on the virion surface. The mAb 7C4 epitope
      was assigned to the region comprising amino acids 517-537 on the p15E component
      of PERV. In contrast to mAb 8E10, the 7C4 mAb bound native PERV inefficiently
      suggesting that its epitope is accessible only after the virus interacts with its
      receptor. Finally, both mAbs variable regions were cloned and nucleotide sequence
      determined. All together, these results reveal that both mAbs 8E10 and 7C4
      effectively neutralize PERV infection and may be used as a mean to prevent PERV
      infection in patients receiving xenotransplantation.

PMID- 17222435
TI  - Lactoferrin, a glycoprotein with immunomodulatory and mast cell stabilising
      properties, in skin of horses suffering from Culicoides hypersensitivity.
AB  - Lactoferrin (LF), a glycogen of the transferrin family with anti-bacterial and
      immunomodulatory properties, is expressed in various secretions and tissues.
      Cutaneous LF serves as a mast cell stabilising compound, modulates T cell
      activity and is found during IgE-mediated late phase reactions at allergen
      challenged sites. Culicoides hypersensitivity (CHS) in horses is a common IgE
      mediated allergic dermatitis, characterised by an early and late phase cutaneous
      reaction upon allergen challenge. The aim of the study presented here was to
      examine whether LF mRNA expression in skin biopsies from horses affected by CHS
      prior to and 4h following intradermal challenge with a commercial C. nubeculosus
      extract is modified in comparison to skin biopsies from non-affected horses. In
      order to obtain reliable data, real time PCR was performed and genes of interest
      were normalized using three different housekeeping genes, beta-actin, GAPDH, beta
      2-microglobulin. In comparison to non-affected horses, higher variation in LF
      mRNA levels both prior to and post-intradermal challenge with C. nubeculosus
      extract was seen in horses affected by CHS. However, the statistical analysis
      demonstrated that LF mRNA expression was not significantly different between CHS
      affected and non-affected horses prior to intradermal challenge with C.
      nubeculosus extract. Intradermal injection of C. nubeculosus extract did not
      result in local upregulation of LF mRNA at 4h post-injection. LF mRNA expression
      was therefore not significantly different pre- or post-intradermal challenge with
      C. nubeculosus extract in either group. Our data indicate that clinically normal
      skin of horses affected by CHS is not characterized by modified maintenance
      levels of LF mRNA. In contrast to human skin allergen challenged sites, LF mRNA
      levels in horses affected by CHS are not significantly different to that of
      control sites at 4h post-injection of C. nubeculosus extract.

PMID- 17222438
TI  - Efficient induction of HIV-1 replication in latently infected cells through
      contact with CD4+ T cells: involvement of NF-kappaB activation.
AB  - Reservoir cells latently infected with HIV-1 pose one of the major obstacles that
      hamper ultimate eradication of HIV-1 from infected patients. In this report, we
      showed that direct contact with MOLT-4 T cells induced HIV-1 replication in J(22)
      HL-60 latently infected cells without any additional stimulus. Neutralization
      experiments revealed that pro-inflammatory cytokines, whose production was
      increased following cell-cell contact, were unlikely to be primarily involved in
      the induced HIV-1 replication. Cell-cell contact, but not soluble components in
      the culture supernatant, caused a rapid phosphorylation and degradation of
      IkappaBalpha, which led to elevated NF-kappaB DNA binding activity in J(22)-HL-60
      cells. Furthermore, forced expression of a super-repressor form of IkappaBalpha
      or pretreatment with ritonavir efficiently blocked the activation of NF-kappaB
      and HIV-1 replication in J(22)-HL-60 cells co-cultured with MOLT-4 T cells.
      Moreover, either resting or PHA stimulated primary CD4(+) T cells induced HIV-1
      replication in J(22)-HL-60 cells in a similar way with that of MOLT-4 cells.
      These results indicated that direct contact with CD4(+) T cells induced HIV-1
      replication in latently infected cells and provide insight into the molecular
      mechanism of virus release from myeloid progenitor cells latently infected with
      HIV-1.

PMID- 17222437
TI  - Efficient vagina-to-lower respiratory tract immune trafficking in a murine model
      of influenza A virus infection.
AB  - Effective vaccination strategies for infectious diseases take into account the
      induction, long-term maintenance and recall of memory T-cell populations. To
      understand the immunological cross-talk within the mucosal compartments, we
      compared intranasal to vaginal immunization and demonstrated that vaginal
      infection of BALB/c mice with influenza A virus provides protective mucosal
      immunity against both homosubtypic and heterosubtypic virus challenge in the
      respiratory tract. We found that, prior to the viral challenge, in vaginally
      primed mice, antigen-specific CD8+ T cells were not detected in the lung airways
      and levels of serum antibodies were lower than those observed in intranasally
      immunized mice. However, following pulmonary challenge, NP147-specific CD8+ T
      cells were recruited and amplified in vaginally primed mice to the same extent as
      those in intranasally primed mice. Thus, the long-term memory immune response
      elicited by vaginal immunization with influenza virus is efficiently recalled and
      offers reasonable protection against infection in the respiratory tract.

PMID- 17222439
TI  - Environmental release and mass flux partitioning of PCDD/Fs during normal and
      transient operation of full scale waste to energy plants.
AB  - The paper reports on global release and mass partitioning in the flux of residues
      of PCDD/Fs, evaluated with dedicated field campaigns at a municipal solid waste
      incineration plant during normal and transient operation. Results are compared
      with those obtained in other installations equipped with furnaces, energy
      recovery options and flue gas treatment technologies representative of most of
      the European incineration plants currently in operation. Levels of the pollutants
      of interest were determined in all the solid, liquid and gaseous residues
      produced by every single facility, and the results analysed in terms of the
      effects arising from the fed waste and the configuration of the plant. PCDD/Fs
      total release between 1.5 and 45 microg I-TEQ per ton of burned waste was
      evaluated, with lower values resulting from the adoption of catalytic conversion
      process for flue gas treatment. Most of the mass flux emitted is associated with
      solid residues deriving from activated carbon PCCD/F dry removal options, with
      significant contributions also from fly ash produced by particulate removal
      devices located immediately downstream the boiler and from scrubber blowdowns
      treatment sludge. During transient operating conditions the dioxin total release
      may increase by 50% with comparison to steady-state functioning.

PMID- 17222440
TI  - Immunologic effects of perinatal exposure to dioxins, PCBs and organochlorine
      pesticides in Japanese infants.
AB  - Effects of perinatal exposure to dioxins, PCBs and organochlorine pesticides on
      lymphocyte subsets were investigated in the peripheral blood from 101 Japanese
      infants with approximately 10 months of age. Perinatal exposure to these
      organochlorine compounds were estimated by their contamination levels in the
      breast milk of the mothers. Lymphocyte subsets such as CD16+, HLA-DR+, CD4+,
      CD4+8+, CD8+, CD3+ and CD20+ cells in peripheral venous blood were assessed in a
      subgroup of 92 infants. Greater exposures to HCE, chlordane and dioxins were
      significantly associated with the increase in the percentages of CD8+ and CD3+ T
      lymphocytes and CD4+/CD8+ T cell ratios, respectively. In addition, higher HCH
      exposure was also associated with a decrease in the percentage of HLA-DR+ T
      lymphocytes. Furthermore effects of dioxins, DDT and PCBs on the percentage of
      CD16+ T lymphocyte were more pronounced by the combined exposure of dioxins and
      PCBs or by the combined exposure of DDT and PCBs. Effects of HCE on the
      percentages of CD8+ T lymphocyte were also more pronounced by the combined
      exposure of HCE and chlordane. In conclusion, our study suggests that greater
      exposures to dioxins, PCBs and organochlorine pesticides determined in this study
      (except dieldrin) influence the immune system of Japanese infant, although the
      clinical significance of these changes is uncertain.

PMID- 17222441
TI  - TCDD alters PKC signaling pathways in developing neuronal cells in culture.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to induce neurodevelopmental
      deficits such as poor cognitive development and motor dysfunction. However, the
      mechanism of TCDD-mediated neurotoxicity remains unclear. Since PKC signaling is
      one of the most pivotal events involved in neuronal function and development, we
      analyzed the effects of TCDD on the PKC signaling pathway in cerebellar granule
      cells derived from PND-7 rat brain. Immunoblot analysis revealed the presence of
      PKC-alpha, betaII, delta, epsilon, lambda and iota in both cytosol and membrane
      fractions of cerebellar granule cells, but PKC-gamma was below the detectable
      level. TCDD induced a significant translocation of PKC-alpha, -betaII and 
      epsilon from cytosol to membrane fraction (p<0.05) and a marginal translocation
      of PKC-delta at high dose only (p<0.1). It also increased RACK-1, an adaptor
      protein for PKC, in a dose-dependent manner. Exposure to TCDD induced a dose
      dependent increase of both [3H] PDBu binding and the intracellular calcium level.
      The results suggest that the selective PKC isozymes and RACK-1 are involved in
      TCDD-mediated signaling pathway and these proteins may be possible molecular
      targets in neuronal cells for TCDD exposure. Our study provides basic data to
      understand mechanism of TCDD-induced neurotoxicity with respect to PKC signaling
      pathway and a scientific basis for improving the health risk assessment of
      neurotoxicants by identifying intracellular target molecules in neuronal cells.

PMID- 17222444
TI  - Nuclear magnetic resonance spectral characterization and semi-empirical
      calculations of conformations of alpha- and gamma-1,2,5,6,9,10
      hexabromocyclododecane.
AB  - The full 1H and 13C NMR spectral characterization of alpha- and gamma
      1,2,5,6,9,10-hexabromocyclododecane (HBCD) is reported in this paper. The use of
      various NMR experiments, an analysis of the magnitude of the NMR chemical shifts
      and coupling constants, and computer modeling has enabled the visualization of
      the three-dimensional structures for both the alpha- and gamma-diastereomers.
      This information may provide insight into the different behavior of the alpha-
      and gamma-HBCD diastereomers in the environment.

PMID- 17222443
TI  - Health risk analysis of PCDD/F emissions from MSW incineration: comparison of
      probabilistic and deterministic approaches.
AB  - Incremental lifetime health risks due to polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/F) emitted from municipal waste incineration (MSWI)
      facilities were evaluated for resident population in the area of the plant. Risk
      assessment was performed through a multipathway combined
      probabilistic/deterministic approach for analyzing the effects of uncertainty and
      intrinsic variability of the main PCDD/F emission related parameters on final
      predicted values. Exposure through direct inhalation of contaminated air, soil
      ingestion, soil dermal contact and diet were considered, with the propagation of
      the variability of input parameters throughout the evaluation performed with
      Monte Carlo simulation techniques. The application to a case study representative
      of two different technological scenarios (modern facilities equipped with BAT -
      Best Available Technology - and older incinerators) in a location site typical of
      Northern Italy situation results in median values of the maximum individual
      excess risk on the order of 10(-9) and 10(-7) for most recent and older plant
      configurations, respectively. Corresponding ratios for the 90th and 10th
      percentile values are around 7 and 9. Individual risk estimates derived for the
      same scenarios from conventional deterministic approaches, where large
      conservative assumptions are normally adopted for compensating the lack of
      knowledge about uncertainty, are essentially comparable with maximum values
      resulting from the probabilistic approach, thus leading to situations with
      extreme and very low probabilities of occurrence. PCDD/F health risks from MSWI
      emissions might thus result largely overestimated if real emission
      characteristics are not properly considered in the assessment procedure.
      Sensitivity analysis for identifying the contribution of different input
      parameters on final predicted risk variance indicates, for the area considered in
      the simulation, a prevailing influence of PCDD/F stack concentration, with
      exposures arising from soil deposition phenomena substantially negligible: this
      latter result further points out the requirements for a very careful
      identification of base input data values for PCDD/F stack concentrations, at
      least for those situations where plants are located nearby urban areas.

PMID- 17222442
TI  - Fish from industrially polluted freshwater as the main source of
      organochlorinated pollutants and increased frequency of thyroid disorders and
      dysglycemia.
AB  - In a certain area of Michalovce district in East Slovakia, heavy industrial
      pollution by polychlorinated biphenyls (PCBs) developed in 1955-1984 and very
      high PCB levels in environmental and human samples are still persisting.
      Recently, a total of 2045 adults from this and the surrounding background
      pollution area have been examined using questionnaire data, thyroid volume by
      ultrasound (ThV), urinary iodine and serum levels of 15 PCB congeners,
      hexachlorobenzene (HCB), 2,2'-2-bis(4-chlorobiphenyl)-1,1-dichloroethylene (DDE),
      2,2'-bis(4-chlorophenyl)-1,1,1-trichloroethane (DDT), alpha-, beta- and gamma
      hexachlorocyclohexane (HCH), thyrotropin (TSH), free thyroxine (FT4), anti
      thyroperoxidase antibodies (TPOab) and fasting glucose. As based on our previous
      findings of strikingly high level of PCBs in fish from high pollution area (e.g.
      mean level of 375430 ng/g lipid) and considerably lower, but still relatively
      high level in background pollution area (e.g. mean PCB level of 5150 ng/g), the
      information on the frequency of fish meals and approximate annual consumption of
      fish from local waters was obtained by questionnaires. The association of
      contaminated fish consumption with very high blood levels of PCBs, DDE and HCB
      and increased ThV as well as with increased frequency of positive TPOab, high
      values of FT4 and impaired fasting glucose (IFG) was found. These associations
      were also confirmed in 16 marital pairs from high pollution area with very high
      PCB level in both members associated with high fish consumption. It was concluded
      that, due to persistent heavy pollution of waters, soil and food chain namely by
      PCBs, but also by pesticides (e.g. DDE and HCB) resulting from their previous
      extensive use in agriculture, the fish from local waters still remains the most
      important source of these toxic pollutants which results in considerable adverse
      health effects.

PMID- 17222445
TI  - Dioxin screening in fish product by pattern recognition of biomarkers.
AB  - Two alternative, cost- and time-effective dioxin screening methods relying on two
      categories of potential lipid biomarkers were investigated. A dioxin range
      varying from 1.1 to 47.1 pg PCDD/F TEQ-WHO/g lipid using 64 fish meal samples was
      used for model calibration. The methods were based on multivariate models using
      either (1) fatty acid composition monitored by GC-FID or (2) fluorescence
      landscape signals analysed using the PARAFAC model and in both cases predicting
      dioxin content as pgPCDD/F TEQ-WHO/g lipid. In both cases, Partial Least Squares
      (PLS) regression was performed for predicting the dioxin content of a sample. The
      GC-FID data analyses was based on automatic peak alignment and integration,
      enabling extraction of the area of 140 peaks from the gas chromatograms, as
      opposed to the 31 fatty acids usually considered for fish oil characterisation.
      In addition to classic PLS employing the whole dataset for calibration, a two
      step local PLS modeling approach was performed based upon an initial selection of
      k number of calibration samples providing the best match to the prediction sample
      using a so-called k Nearest Neighbors (kNN) approach, then followed by PLS
      calibration on these kNN selected samples for dioxin prediction. Fluorescence
      spectroscopy offers a promising non-invasive and ultra-rapid technique, with less
      than two minutes analysis time. However, fluorescence spectroscopy using the
      pattern recognition "kNN-PLS" yielded a correlation of 0.76 (r2) and a high root
      mean square error of prediction of 11.4 pg PCDD/F TEQ-WHO/g lipid. The
      predictions were improved when the PLS calibration was performed on all the
      sample with a root mean square error of prediction of 7.0 pg PCDD/F TEQ-WHO/g
      lipid. Unfortunately, these results failed to demonstrate the potential of
      fluorophore monitoring as a screening method. In contrast, the overall best
      screening performance was obtained with the fatty acid profile, when the kNN-PLS
      combination employed for pattern recognition (kNN) all the areas of the 140
      detected peaks and the PLS regression used the areas of 46 selected peaks. This
      "kNN-PLS" prediction with three latent variables and based upon the 12 nearest
      neighbors selected out of the 64 x 2 fatty acid profiles (duplicate analyses),
      yielded a correlation of 0.85 (r2) and a root mean square error of prediction of
      2.1 pg PCDD/F TEQ-WHO/g lipid and resulted in a total analysis time of one and
      half hour per sample.

PMID- 17222446
TI  - Dioxin contamination in soils of Southern Vietnam.
AB  - Dioxin is the common name for polychlorinated dibenzo-p-dioxins (PCDDs) and
      polychlorinated dibenzofurans (PCDFs), and is abbreviated as PCDD/Fs. In the case
      of Southern Vietnam, is of high concern dioxin contamination in the areas
      affected by past-use chemical defoliants. Our study related to the zone
      considered as a "hot spot"--Bien Hoa Airbase and surrounding areas (Bien Hung
      Lake). Although the war ended over 30 years ago, the adverse effects on this
      territory still continue. Soil and sediment were selected for our research as
      they act as a sink for PCDD/Fs. The samples were taken and analyzed in CECOTOX
      laboratory following certified procedures. The total amounts of PCDD/Fs (2,3,7,8
      related congeners) in the samples were converted into WHO-TEQ and compared with
      standard values proposed by Canadian environmental quality guidelines. The
      obtained data shows a relatively high risk (up to 20.4 times higher than
      (probable effect level) PEL value for sediment and 46 times higher than standard
      value for soil). The research is continuing on the assessment of dioxin transport
      in food chain. Moreover, considering the obtained data a complete solution should
      be found urgently to solve the problem of dioxin contamination in the studied
      areas.

PMID- 17222447
TI  - Temporal trends and spatial distribution of PCDD, PCDF, and PCB in pine and
      spruce shoots.
AB  - In Germany, there is a lack of consistent and comparable data for the time
      dependent behaviour and spatial distribution of dioxin-like and indicator PCB in
      ambient air, deposition and plants. The aim of this study was to improve the data
      on PCDD/PCDF, dioxin-like PCB and non dioxin-like PCB in spruce and pine shoots
      from different locations and years by retrospective monitoring. The survey was
      conducted with archived samples of one-year old spruce shoots (Picea abies) and
      pine shoots (Pinus sylvestris) from the German environmental specimen bank. Two
      sets of samples from locations in urbanized areas in western and eastern Germany
      (Warndt and Duebener Heide Mitte, respectively) were investigated as time series.
      Additionally, spruce shoots from seven different rural locations sampled in the
      years 2000-2004 were analyzed in order to get an overview about the spatial
      distribution of PCB and PCDD/PCDF. The analytical results of the samples from the
      two urbanized areas clearly show that the atmospheric contamination with PCDD and
      PCDF has declined by about 75% between 1985 and 1997 at Warndt and about 40%
      between 1991 and 1997 at Duebener Heide. However, concentrations stayed virtually
      constant at both locations from 1997 to 2004 at a level of about 1 ng WHO-TEQ/kg
      dry matter (d.m.). Similarly, the investigation of spruce shoots from rural
      locations from 2000 to 2004 did not reveal a temporal trend at any site.
      PCDD/PCDF levels were between 0.1 and 1.0 ng WHO-TEQ/kg d.m. At the urbanized
      location Warndt the six indicator PCB as well as the 12 dioxin-like PCB according
      to WHO revealed a significant decline by more than 75% between 1985 and 1999.
      Thereafter, PCB levels stayed virtually constant. At the location Duebener Heide
      an overall decrease of PCB concentrations in pine shoots of about 60% was
      detected between 1991 and 2004. Spruce shoots from all locations showed a
      relevant contribution of dioxin-like PCB to the total WHO toxicity equivalent
      (PCDD/PCDF+PCB). In most samples, the contribution of dioxin-like PCB was between
      21% and 41%. The TEQ contribution of PCB in the samples from three rural sites
      was higher and similar to the TEQ value of PCDD/PCDF. The investigated pine
      shoots from the urbanized site Duebener Heide showed a 15-28% contribution of
      dioxin-like PCB to total TEQ and thus lower than in spruce shoots from different
      locations. In all samples except one PCB 126 contributed to more than 80% to the
      PCB-TEQ.

PMID- 17222448
TI  - SENEQUE: a multi-scaling GIS interface to the Riverstrahler model of the
      biogeochemical functioning of river systems.
AB  - The Riverstrahler model describes the biogeochemical functioning of an entire
      river system, from 100 to 100,000 km(2) or more, taking into account the
      constraints set by the morphology of the drainage network, the
      meteorological/hydrological conditions, and the inputs of material from point and
      non-point sources in the watershed. This tool has been applied for research
      purpose to several river systems differing in terms of hydrological regime and
      anthropogenic influences. In order to improve its capabilities and its generic
      dimension, as well as to develop a user-friendly interface allowing its transfer
      to non-specialist users including managers, the model has been coupled to a GIS
      interface. This gives the user the possibility to visualize the available
      geospatial database, to select the best geographical representation of the
      drainage network, to automatically prepare the corresponding input files required
      for the model, to pilot the model calculation and to visualize the results. The
      coupling with a GIS interface has considerably improved the capabilities of the
      Riverstrahler model. The code of the model is now entirely generic and can be run
      on any river system for which a suitable database is available. Its spatial
      resolution can be adapted to the requirement of the relevant problem, from the
      highest level, where each elementary watershed is individualized, to the lower
      level, where the whole basin is idealized as one basin with tributaries of each
      order having the same characteristics. As an illustration of the new
      potentialities offered by the coupling of Riverstrahler with a GIS through the
      SENEQUE interface, the results of a same modeling scenario are compared at
      different spatial resolutions. For the first time, with on-line coupling to a
      geodatabase, the effect of increasing the spatial resolution of the drainage
      network representation on the performance of the Riverstrahler model has been
      examined. At the outlet of the basin, the water quality results were found
      invariant to a large degree, whatever the details of its representation in the
      calculations. This result justifies the use of a low resolution representation of
      the upstream watershed when results are required only at the outlet of the basin.

PMID- 17222449
TI  - Cadmium exposure pathways in a population living near a battery plant.
AB  - OBJECTIVES: The objectives of the present study were to assess the relative
      impact of different pathways of environmental cadmium (Cd) exposure and to
      evaluate the contribution from locally produced vegetables and root crops to the
      total dietary intake of Cd. METHODS: Cadmium in urine was determined for 492
      individuals living near a closed down battery factory in Sweden. For each
      individual we created an environmental exposure-index based on Cd emissions to
      ambient air and number of years living at various distances from the plant. This
      information as well as dietary data were collected via questionnaires. Samples of
      soil, carrots and/or potatoes were collected from 37 gardens and analysed for Cd
      concentration. RESULTS: Eating home grown vegetables/potatoes, environmental Cd
      exposure-index, female gender, age above 30 years and smoking more than one pack
      of cigarettes daily for at least 10 years were found to be significantly
      associated with increased urine concentrations of Cd (UCd>1.0 nmol/mmol
      creatinine). We found a statistically significant relation between Cd in urine
      and environmental Cd-exposure-index in persons eating home grown
      vegetables/potatoes regularly. Cd concentrations in home grown carrots, potatoes
      and in garden soil were highest in the area closest to the factory. Daily
      consumption of potatoes and vegetables cultivated in the vicinity of the closed
      battery factory was estimated to increase Cd intake by 18-38%. CONCLUSION: The
      present study shows that consumption of locally grown vegetables and root crops
      was an important exposure pathway, in subjects living near a nickel-cadmium
      battery plant, whereas direct exposure via ambient air was less important.

PMID- 17222450
TI  - Waist circumference and weight following smoking cessation in a general
      population: the Inter99 study.
AB  - OBJECTIVE: Central obesity is an independent risk factor of mortality. Change in
      waist circumference after smoking cessation has not been previously reported in a
      population-based prospective study of both sexes. METHODS: Population-based
      study, Inter99, 1999-2001 in Copenhagen, Denmark. 2408 daily smokers completed
      questionnaires and had their waist circumference and weight measured. Of these,
      221 biochemically verified non-smokers and 1122 continuous smokers attended 1
      year follow-up and had their waist circumference and weight measured. RESULTS:
      The mean increase in waist circumference was 3.88 cm (+/-5.4 cm) and 42% of the
      quitters had increased their waist circumference by > or = 5 cm. Quitters with
      high baseline tobacco consumption (OR 1.05, 95% CI=1.0-1.1) and quitters with
      self-reported reduced physical activity (OR 3.4, 95% CI=1.5-7.7) were more likely
      to have substantially increased waist circumference. The mean weight gain in
      quitters was 4.22 kg (+/-4.3 kg) and 41% had gained at least 5 kg. Female
      quitters gained more weight and had a higher increase in waist circumference than
      men. Abstinence from smoking was the most important predictor of substantial
      weight gain and substantial increase in waist circumference. CONCLUSIONS: Smoking
      cessation resulted in substantial increase in weight and central fat, which might
      attenuate some of the beneficial effects of smoking cessation. Quitters who
      reduced their physical activity and persons with high baseline tobacco
      consumption were more likely to have had a substantial increase in abdominal fat.
      Abstinence from smoking was the most important predictor of short-term weight
      gain and increase in waist circumference. It is a challenge for future smoking
      cessation interventions to achieve a combination of high quit rates and weight
      control.

PMID- 17222451
TI  - Weight concerns and smoking in a general population: the Inter99 study.
AB  - OBJECTIVE: No previous studies have explored weight concerns in relation to
      smoking habits, or investigated how weight concerns affect smoking cessation in a
      general population. METHOD: Inter99 is a population-based lifestyle
      interventional study, conducted in 1999-2001 in Copenhagen, Denmark, comprising
      30-60 year old men and women. All daily smokers (N=2408) were offered help to
      quit. The baseline investigation (N=6784) was used for analysing associations of
      smoking status with weight concerns (cross-sectional design). To analyse how
      weight concerns affected smoking cessation we included the 1387 daily smokers
      attending 1-year follow-up; 221 of these were verified quitters (longitudinal
      design). RESULTS: Daily smoking men and women had a significantly lower body mass
      index than never smokers (men: 3%, women 5%) but reported to be significantly
      less concerned of their weight (men: OR=0.64, 95%CI=0.4-0.9), women: 0.78(0.6
      1.0)). Ex-smoking normal weight women were significantly more likely to be
      frequently concerned of their weight than never smoking normal weight women
      (OR=2.06, 95CI%=1.6-2.7). Fifty-two percent of the women and 32% of the men with
      a previous quit attempt reported that weight gain was a reason for relapse.
      Neither weight concerns nor eating patterns were predictive of point abstinence
      at 1-year follow-up. CONCLUSION: Smokers are believed to be very concerned of
      their weight but in this population-based study, daily smokers more frequently
      ate what they wanted, had a lower BMI and were significantly less concerned of
      their weight than never smokers. Weight concerns and eating patterns did not
      predict abstinence at 1-year follow-up. It seems that weight gain and weight
      concerns are independent factors.

PMID- 17222452
TI  - Preparation of alginate-quaternary ammonium complex beads and evaluation of their
      antimicrobial activity.
AB  - Alginate-quaternary ammonium complex beads with antimicrobial activity were
      prepared by the reaction of sodium alginate (SA) with 3-(trimethoxysilyl)propyl
      octadecyldimethylammonium chloride (TSA) in acid solution, followed by
      crosslinking with CaCl(2). FTIR spectroscopy analysis showed that the resulting
      complex was formed mainly through covalent bonds between the hydroxyl groups of
      SA and the methoxysilyl groups of TSA. The complex beads exhibited a maximum
      swelling of 20% in water at 37 degrees C and were not hydrolyzed in water during
      experiments lasting for 30 days. The in vitro antimicrobial activity of the
      complex beads was evaluated against four species of bacteria and fungi. The test
      microorganisms were completely eliminated within 20 min when treated with 5%
      (v/v) complex beads, which showed a wide spectrum of excellent antimicrobial
      activity. The antimicrobial activity of the complex beads was retained after 10
      cycles of washing and drying. The present results indicate that these SA-TSA
      complex beads are a new type of insoluble cationic polymer that can kill or
      remove microorganisms in water by mere contact without releasing the reactive
      agent.

PMID- 17222453
TI  - Formation of osteogenic colonies on well-defined adhesion peptides by freshly
      isolated human marrow cells.
AB  - Bone graft performance can be enhanced by addition of connective tissue
      progenitors (CTPs) from fresh bone marrow in a manner that concentrates the CTP
      cell population within the graft. Here, we used small peptide adhesion ligands
      presented against an otherwise adhesion-resistant synthetic polymer background in
      order to illuminate the molecular basis for the attachment and colony formation
      by osteogenic CTPs from fresh human marrow, and contrast the behavior of fresh
      marrow to many commonly used osteogenic cell sources. The linear GRGDSPY ligand
      was as effective as tissue culture polystyrene in fostering attachment of culture
      expanded porcine CTPs. Although this GRGDSPY peptide was more effective than
      control peptides in fostering alkaline phosphatase (AP)-positive colony formation
      from primary human marrow in 5 of the 7 patients tested, GRGDSPY was as effective
      as the control glass substrate in only one patient of 7. Thus, the peptide
      appears capable of enabling osteoblastic development from only a subpopulation of
      CTPs in marrow. The bone sialoprotein-derived peptide FHRRIKA was ineffective in
      fostering attachment of primary culture-expanded pig CTPs, although it was as
      effective as GRGDSPY in fostering AP-positive colonies from fresh human marrow.
      This study provides insights into integrin-mediated behaviors of CTPs and
      highlights differences between freshly isolated marrow and culture-expanded
      cells.

PMID- 17222454
TI  - Three new Cu(II) and Cd(II) complexes with 3-(2-pyridyl)pyrazole-based ligand:
      syntheses, crystal structures, and evaluations for bioactivities.
AB  - Three new complexes [Cu(L)(2)(NO(3))](NO(3))(H(2)O)(1/2)(CH(3)OH)(1/2) (1),
      [Cd(L)(2)(NO(3))(2)](H(2)O)(3) (2) and
      [Cd(L)(2)(ClO(4))(CH(3)OH)](ClO(4))(H(2)O)(1/4)(CH(3)OH) (3) (L=1-[3-(2
      pyridyl)pyrazol-1-ylmethyl]naphthalene) were synthesized and characterized by
      elemental analyses, IR and X-ray diffraction analysis. Among them, the Cu(II) and
      Cd(II) ions were both coordinated by four N donors from two distinct L ligands
      via N,N-bidentate chelating coordination mode. Additional weak interactions, such
      as the face-to-face pi-pi stacking and C-Hcdots, three dots, centeredO H-bonding
      interactions, linked the mononuclear unit into 1D chain and further into 2D
      network. Complexes 1-3 were subjected to biological assays in vitro against six
      different cancer cell lines. All of them exhibited cytotoxic specificity and
      notable cancer cell inhibitory rate. The interactions of 1-3 with calf thymus DNA
      were investigated by thermal denaturation, viscosity measurements,
      spectrophotometric and electrophoresis methods. The results indicate that these
      complexes bound to DNA by intercalation mode via the ligand L and had different
      nuclease activities, which were in good agreement with their DNA-binding
      strength. Moreover, the central metal ions of 1-3 played a vital role in DNA
      binding behaviors, DNA-cleavage activities and cytotoxicities, whereas the
      contribution of the different counter anions to their bioactivities also should
      not be ignored.

PMID- 17222455
TI  - DNA interaction of new copper(II) complexes with sulfonamides as ligands.
AB  - New copper(II) complexes with sulfonamide ligands have been prepared and
      characterized. Sulfonamide ligands were prepared through a reaction between 8
      aminoquinoline and either 2-mesitylene (Hqmesa), 4-tert-butylbenzene (Hqtbsa), or
      alpha-toluene (Halphaqtsa) sulfonyl chlorides. The structural analysis carried
      out for complex [Cu(alphaqtsa)(2)] indicated that the local environment of the
      Cu(II) cation is between a square planar and a tetrahedral geometry, with
      stacking of the benzene rings of the sulfonyl ligands between neighbor molecules.
      Powder EPR spectra at room temperature gave rhombic spectra for the
      [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] complexes and an axial spectrum for the
      [Cu(qtbsa)(2)] complex, probably due to the steric hindrance of the methyl
      groups. Complexes [Cu(alphaqtsa)(2)] and [Cu(qmesa)(2)] are artificial chemical
      nucleases that degrade DNA in the presence of sodium ascorbate. A study of the
      radical scavengers revealed that the ROS (reactive oxygen species) involved in
      the DNA damage were hydroxyl, singlet oxygen-like species, and superoxide anion.

PMID- 17222456
TI  - The role of chondroitin sulfate proteoglycans in regeneration and plasticity in
      the central nervous system.
AB  - Chondroitin sulfate proteoglycans (CSPGs) consist of a core protein and
      glycosaminoglycan (GAG) chains. There is enormous structural diversity among
      CSPGs due to variation in the core protein, the number of GAG chains and the
      extent and position of sulfation. Most CSPGs are secreted from cells and
      participate in the formation of the extracellular matrix (ECM). CSPGs are able to
      interact with various growth-active molecules and this may be important in their
      mechanism of action. In the normal central nervous system (CNS), CSPGs have a
      role in development and plasticity during postnatal development and in the adult.
      Plasticity is greatest in the young, especially during critical periods. CSPGs
      are crucial components of perineuronal nets (PNNs). PNNs have a role in closure
      of the critical period and digestion of PNNs allows their re-opening. In the
      adult, CSPGs play a part in learning and memory and the hypothalamo
      neurohypophysial system. CSPGs have an important role in CNS injuries and
      diseases. After CNS injury, CSPGs are the major inhibitory component of the glial
      scar. Removal of CSPGs improves axonal regeneration and functional recovery.
      CSPGs may also be involved in the pathological processes in diseases such as
      epilepsy, stroke and Alzheimer's disease. Several possible methods of
      manipulating CSPGs in the CNS have recently been identified. The development of
      methods to remove CSPGs has considerable therapeutic potential in a number of CNS
      disorders.

PMID- 17222457
TI  - Spectroscopic, viscositic and electrochemical studies of DNA interaction with a
      novel mixed-ligand complex of nickel (II) that incorporates 1-methylimidazole and
      thiocyanate groups.
AB  - A novel mixed-ligand nickel(II) complex that contains 1-methylimidazole and
      thiocyanate, Ni(NCS)(2)(Mim)(4) (Mim=1-methylimidazole), was synthesized and its
      structure was determined by X-ray crystallography, IR spectrum and elemental
      analysis, etc. Its DNA-binding properties were studied by electronic absorption
      spectral, viscositive and electrochemical measurements. The absorption spectral
      and viscositive results suggest that the nickel(II) complex binds to DNA via
      partial intercalation. The addition of DNA results in the decrease of the peak
      current of the nickel(II) complex proved their interaction. The slight
      differences of peak profiles and electrochemical parameters between free and DNA
      bound Ni(NCS)(2)(Mim)(4) showed the formation of an electrochemical inactive
      complex between Ni(NCS)(2)(Mim)(4) and DNA. The binding site and binding constant
      of the complex to DNA were determined by electrochemical titration method.

PMID- 17222458
TI  - Factors associated with major depressive disorder occurring after the onset of
      obsessive-compulsive disorder.
AB  - BACKGROUND: We aimed to investigate the correlates of major depressive disorder
      (MDD) occurring after the onset of obsessive-compulsive disorder (OCD). METHODS:
      Forty-three OCD patients who developed MDD after the onset of OCD (OCD-MDD group)
      and 67 OCD patients without MDD (non-MDD, NMDD group) were compared with regard
      to sociodemographic characteristics, clinical history, symptom severity, types of
      obsessions and compulsions, insight degree, comorbid axis I and axis II diagnosis
      and quality-of-life level. RESULTS: The OCD-MDD group scored significantly higher
      on measures of obsessions, compulsions and depression severity than did the NMDD.
      Significantly more aggressive obsessions were identified in the OCD-MDD group
      than in the NMDD group. The OCD-MDD group was also significantly more likely than
      the NMDD group to have generalized anxiety disorder (GAD). There was no
      significant difference in the rate of personality disorders between the groups.
      The OCD-MDD group reported significantly lower levels of quality of life (QOL) in
      the domains of physical health, psychological health and social relationships.
      Depression severity was associated with obsession but not with compulsion
      severity. In a logistic regression model, obsession severity, presence of GAD and
      aggressive obsessions emerged as the factors associated with the occurrence of
      MDD. LIMITATIONS: To exclude ineligible patients, we gathered the information
      about past mood episodes cross-sectionally. CONCLUSIONS: These results suggest
      that psychopathological processes mediated by specific obsessions as well as
      excessive anxiety and worries may render the neurocircuities more vulnerable to
      the development of MDD. The occurrence of MDD in OCD cannot sufficiently be
      explained as a secondary complication to the disability of OCD.

PMID- 17222459
TI  - The role of altruistic behavior in generalized anxiety disorder and major
      depression among adults in the United States.
AB  - BACKGROUND: Although previous studies found protective associations of altruistic
      behaviors (AB) with positive mental health outcomes, these studies were limited
      to unspecified mental health outcomes and non-nationally representative studies.
      It is needed to examine the association of AB with generalized anxiety disorder
      (GAD) and major depression (MD). METHODS: Data collected from the National Survey
      of Midlife Development in the United States (MIDUS) in 1995-1996 for those aged
      between 25 and 74, who completed both the telephone survey and the self
      administered questionnaire (N=4,242) were analyzed. GAD and MD were measured by
      telephone on the basis of the Composite International Diagnostic Interview, while
      AB was measured by the questionnaire. Multivariate logistic regression was used
      to observe the independent effects of AB on GAD and MD. RESULTS: AB had a weak
      protective effect on GAD. However, AB had a significant and independent harmful
      effect on MD after controlling for demographic variables (gender, age, working
      status, and marital status). LIMITATIONS: Since the MIDUS study is cross
      sectional, the causality of the associations between AB with GAD and MD cannot be
      established. Other possible confounders that explain these associations were not
      controlled. CONCLUSION: AB might be recommendable to prevent GAD, but on the
      other hand, it could be a risk factor for individuals having MD. Longitudinal
      studies are needed to explore the mechanism of the onset of GAD and MD through
      enhanced AB.

PMID- 17222461
TI  - Neuronal plasticity and neuroregeneration in the skin -- the role of
      inflammation.
AB  - The skin develops probably the densest and most complex innervation of all
      mammalian organs, consisting of sensory and autonomic nerves loaded with a
      plethora of neuropeptides and neurotransmitters. Skin innervation, as well as the
      expression patterns of neurotrophins and their receptors, is subject to dramatic
      changes during not only morphogenesis but also adult tissue remodeling under
      physiological or inflammatory conditions. Bilateral neuroimmune interactions are
      the basis of adaptive responses to tissue remodeling (such as hair cycling),
      psycho-emotional stress or skin inflammation. Dermatitis and hair loss may be
      exacerbated by stress-induced neurogenic inflammation. In addition, selected
      inflammatory skin diseases are associated with increased innervation. Finally,
      inflammatory cytokines influence the cutaneous expression of neurotrophins, as
      well as neurotrophin-induced neurite outgrowth following axotomy. Here, we review
      key studies on bilateral neuroimmune interactions in the skin under both healthy
      and disease conditions to provide a basis for future research on the role of
      inflammation in peripheral nerve regeneration.

PMID- 17222460
TI  - Varied levels of reactivity by different E-selectin/Fc constructs with cutaneous
      lymphocyte-associated antigen (CLA)(+) CD4(+) T cells.
AB  - T cells utilize the vascular adhesion molecule E-selectin to enter inflamed skin.
      T cells identified by the mAb HECA-452 [cutaneous lymphocyte-associated antigen
      (CLA) T cells] are enriched in E-selectin ligand expressing cells. However, the
      proportion of CLA(+) T cells reactive with an E-selectin/Fc chimeric construct,
      as determined by flow cytometry, can vary considerably between studies. One
      important variable in these studies has been the E-selectin/Fc chimera used to
      assess ligand expression. We therefore compared the reactivity of mouse, rat, and
      human E-selectin/Fc from the same widely used commercial source with peripheral
      blood CLA(+) CD4(+) T cells, neutrophils, and the promyelocytic cell line HL-60
      by flow cytometry and by shear flow assays. We observed that the binding
      activities of the different E-selectin/Fc chimeras were considerably different.
      Mouse E-selectin/Fc demonstrated the highest binding activity with human
      neutrophils and HL-60 cells by both assay approaches, whereas human E-selectin/Fc
      demonstrated the lowest binding activity. In addition, mouse E-selectin/Fc
      binding increased essentially in a linear manner with increasing expression of
      CLA by CD4(+) T cells, whereas human and rat E-selectin/Fc binding occurred with
      only a subset of CLA(+) CD4(+) T cells. We conclude that there is substantial
      variability in the reactivity of different E-selectin/Fc constructs, thus caution
      should be used when assessing E-selectin ligand expression with these reagents.
      For instance, the discordance in expression of CLA and E-selectin ligands by T
      cells may in part be due to the E-selectin/Fc construct being used.

PMID- 17222462
TI  - Neurodegeneration in autoimmune demyelination: recent mechanistic insights reveal
      novel therapeutic targets.
AB  - Multiple sclerosis (MS) is the most common chronic demyelinating disease of the
      central nervous system (CNS) and the major cause of neurological disability in
      young adults in Western countries. In spite of intensive research efforts,
      treatment options established to date do not sufficiently prevent the
      accumulation of tissue damage and clinical disability in patients with MS. We
      here describe recently identified molecules responsible for the inflammatory and
      the neurodegenerative processes in MS and its animal model, experimental
      autoimmune encephalomyelitis (EAE), and review new treatment options targeting
      both aspects of this disease.

PMID- 17222463
TI  - Connexin 26 deafness is not always congenital.
AB  - OBJECTIVE: Hearing loss associated with mutations of the GJB2, the gene encoding
      Connexin 26 (Cx26), is described as a prelingual, bilateral, prevalently stable
      sensorineural defect ranging in severity from mild to profound. Despite many
      clinical studies, there is still a limited knowledge about the severity of Cx26
      hearing loss at birth, in the postnatal period or in early infancy; some authors
      have reported about a possible variable age of onset. The aim of this work was to
      investigate the characteristics of Cx26 hearing loss and test the hypothesis of a
      postnatal sudden and severe deterioration of the hearing capacity in cases with
      uncertain age at onset. METHODS: We have studied 79 children with molecularly
      documented biallelic Cx26 hearing loss by evaluating longitudinal audiometric
      characteristics and the results of a questionnaire administered to the parents,
      regarding the auditory behavior of their children at 3 and 6 months of age.
      RESULTS: More than 50% of children with profound hearing loss were described as
      having normal auditory behavior at three months of age, and at least 20% of these
      children were consistently reported by the parents to maintain normal auditory
      development up to 6 months of age. None of the studied children showed
      significant progression in hearing loss from the time of diagnosis through their
      last follow-up. In a few cases these reports were supported by objective
      audiometric evaluations. CONCLUSIONS: Based on these data, we hypothesize that
      Cx26 profound hearing loss may be not always congenital, with the possibility of
      an early window of "functional time" before the final defect is established. The
      hypothesis of an early auditory input makes timing of detection and intervention
      critical to minimize the deleterious effects of a functional deprivation. In a
      near future, the combination of genetic testing with universal neonatal hearing
      screening and audiological surveillance will provide invaluable information about
      the natural history of the most frequent sensory defect in infancy and will
      consequently allow to maximize the quality of intervention.

PMID- 17222464
TI  - The emerging functions of endocannabinoid signaling during CNS development.
AB  - In the postnatal brain, endocannabinoids acting as retrograde messengers regulate
      the function of many synapses. By contrast, the understanding of endocannabinoid
      functions that regulate fundamental developmental processes such as cell
      proliferation, migration, differentiation and survival during patterning of the
      CNS is just beginning to unfold. Increasing the knowledge of basic developmental
      and signaling principles that are controlled by endocannabinoids will provide
      important insights into the molecular mechanisms that establish functional
      neuronal circuits in the brain. Moreover, determining the molecular basis of
      permanent modifications to cellular structure and intercellular communication
      imposed by cannabis smoking during pregnancy will provide novel therapeutic
      targets for alleviating pathogenic changes in affected offspring. Here, we
      summarize recent findings regarding the ontogeny of the endocannabinoid system in
      neurons that sculpt the temporal and spatial diversity of cellular functions
      during CNS development.

PMID- 17222465
TI  - Ca2+ channel alpha2delta ligands: novel modulators of neurotransmission.
AB  - The term 'Ca2+ channel alpha2delta ligands' has recently been applied to an
      evolving drug class that includes gabapentin (Neurontin) and pregabalin (Lyrica),
      and reflects significant progress over the past decade in elucidating the
      mechanism of action of these drugs: a novel, specific action at one of the
      subunits constituting voltage-sensitive Ca2+ channels. Binding of these ligands
      to the alpha2delta subunit is considered to explain their usefulness in treating
      several clinical disorders, including epilepsy, pain from diabetic neuropathy,
      postherpetic neuralgia and fibromyalgia, and generalized anxiety disorder. The
      evidence indicates a relationship between alpha2delta subunit binding and the
      modulation of processes that subserve neurotransmission. This modulation is
      characterized by a reduction of the excessive neurotransmitter release that is
      observed in certain neurological and psychiatric disorders.

PMID- 17222466
TI  - Neuropeptide tyrosine and pain.
AB  - Research during the past two decades supports a complex role for neuropeptide
      tyrosine (NPY) and two of its associated receptors, the Y1 receptor and the Y2
      receptor, in the modulation of pain, in addition to regeneration and survival
      mechanisms at the spinal level. Thus, NPY has been shown to both cause and reduce
      pain, in addition to having biphasic effects. Recent research has focused on the
      distribution of the spinal NPY-mediated system. Here, we propose various possible
      scenarios for the role of NPY in pain processing, based on its actions at
      different sites (axon versus cell body), through different receptors (Y1 receptor
      versus Y2 receptor) and/or types of neuron (ganglion neurons and intraganglionic
      cross-excitation versus interneurons versus projection neurons).

PMID- 17222467
TI  - Use of modified oligonucleotides to compensate for sequence polymorphisms in the
      real-time detection of norovirus.
AB  - Noroviruses are major causative agents of sporadic and outbreak-associated
      nonbacterial gastroenteritis worldwide. Real-time RT-PCR has rapidly become the
      principle means for norovirus detection due to its sensitivity and specificity;
      however sequence variations in the Norovirus genome can cause problems for real
      time chemistries. Using a combination of modified bases and minor groove binder
      conjugated Eclipse hybridization probes, a one step real-time RT-PCR assay was
      designed and optimized to detect norovirus genogroups I and II. Additionally, an
      RNA internal control was incorporated into the assay to monitor nucleic acid
      extraction and amplification inhibition. As part of this study, a combination of
      36 stool and RNA samples were tested and results were compared to a previously
      described TaqMan assay. An overall correlation of 97% was obtained. After 7
      months of clinical testing, a percent positive rate of 39% was determined, with
      genogroup II accounting for 98% of the positives. Overall, the Eclipse assay is a
      sensitive and robust method for detecting and typing norovirus genogroups I and
      II as well as useful for routine clinical testing. Incorporating modified bases
      helps overcome design limitations due to single nucleotide polymorphisms.

PMID- 17222468
TI  - Gender difference in hemodynamic responses of prefrontal area to emotional stress
      by near-infrared spectroscopy.
AB  - Presentation of negative pictures was used as emotional stress to assess gender
      differences in prefrontal area activation in a functional near-infrared
      spectroscopy (NIRS) study. Compared with neutral condition, the response of oxy
      HB for men yielded no significant difference during stress period, but the
      response induced by stress pictures for women showed significant enhancement. It
      was indicated that it is crucial to take gender difference into account when
      negative stimuli are used in functional brain imaging.

PMID- 17222469
TI  - TcrPDEA1, a cAMP-specific phosphodiesterase with atypical pharmacological
      properties from Trypanosoma cruzi.
AB  - Cyclic nucleotide phosphodiesterases (PDEs) catalyze the degradation of cAMP and
      cGMP, and regulate a variety of cellular processes by controlling the levels of
      these second messengers. We have previously described the presence of both a
      calcium-stimulated adenylyl cyclase and two membrane-bound cAMP-specific PDEs
      (one of them strongly associated to the flagellum and the other one with a
      possible vesicular localization) in Trypanosoma cruzi. Here we report the
      identification and characterization of TcrPDEA1, a singular phosphodiesterase of
      T. cruzi which is resistant to the typical phosphodiesterase inhibitors, such as
      IBMX, papaverine and theofylline. TcrPDEA1 is a single copy gene that encodes a
      620-amino acid protein, which is grouped with PDE1 family members, mainly with
      its kinetoplastid orthologs. TcrPDEA1 was able to complement a mutant yeast
      strain deficient in PDE genes, demonstrating that this enzyme is a functional
      phosphodiesterase. TcrPDEA1 is specific for cAMP with a high K(m) value (191.1+/
      6.5 microM). Cyclic GMP neither activates the enzyme nor competes as a substrate.
      In addition, calcium-calmodulin did not affect the kinetic parameters and, as its
      counterpart in T. brucei, magnesium showed to be crucial for its activity and
      stability. Although TcrPDEA1 function remains unclear, its presence points out
      the high complexity of the cAMP signaling in trypanosomatids and the possible
      compartmentalization of the enzymes involved in the cAMP pathway.

PMID- 17222470
TI  - Synthesis and evaluation of a glibenclamide glucose-conjugate: a potential new
      lead compound for substituted glibenclamide derivatives as islet imaging agents.
AB  - The search for novel SUR1-ligands originates from the idea to influence the in
      vivo behaviour by adding new structural moieties to the glibenclamide structure
      while preserving its binding affinity. Important application of novel conjugates
      might be their use as radioactively labelled tracer probes in the non-invasive
      investigation of the islet mass. It is known that the imaging quality of a tracer
      could be improved by increasing its hydrophilicity, which leads to a reduced
      plasma protein binding and diminished the unspecific uptake by various organs. In
      this study the glucose molecule was chosen as a substitute of glibenclamide to
      enhance hydrophilicity. As expected glucose conjugation leads to a 12-fold
      increase of the hydrophilicity. In vitro evaluation showed that the conjugate
      binds with high affinity to SUR1. Interestingly, in vivo the hypoglycaemic action
      of the conjugate was of significant shorter duration compared to glibenclamide.
      In accordance, the conjugate was cleared much faster from the blood stream, due
      to a significant lower plasma protein binding. In conclusion, glycosylation
      proved to be a powerful tool for the development of a high affinity glibenclamide
      ligand with completely different pharmacodynamics. Therefore, the glucose
      conjugate could be a potential lead compound for the design of substituted
      glibenclamide derivatives as islet imaging ligands.

PMID- 17222471
TI  - Appearance of noncompaction-like remodeling of the anatomical right ventricle in
      a middle-aged subject with modified transposition of the great arteries who did
      not undergo surgery.
AB  - We describe noncompaction-like remodeling of the anatomical right ventricle (ARV)
      in a middle-aged subject with modified transposition of the great arteries (TGA).
      A 54 year-old male had been diagnosed with modified TGA at age 40, but no surgery
      was performed. Enhanced multislice CT revealed the ascending aorta coursing left
      of the anterior pulmonary trunk. Furthermore, the myocardium of the ARV appeared
      thickened, but contrast material could be observed in the ARV myocardium, which
      resembled noncompaction of the left ventricle (LV). We speculated trabecular
      development of the ARV, such as a Chiari network, and with TGA, the ARV provided
      systemic circulation through the aorta. The ARV wall may have thickened due to
      systemic pressure load, resulting in reduction of wall motion of the ARV on
      transthoracic echocardiogram. Recent advances in multislice CT imaging have
      revolutionized the exploration of RV anatomy, especially for depicting the three
      dimensional appearance of noncompaction-like remodeling of the ARV in modified
      TGA in addition to transposition of the great arteries.

PMID- 17222472
TI  - Altered left ventricular diastolic filling following a marathon is a reproducible
      phenomenon.
AB  - The present study examined the reproducibility of alterations in left ventricular
      function and cardiac biomarkers in a cohort of athletes following two marathons,
      one year apart. Eight participants in the 2004 and 2005 London Marathons were
      tested pre- and post-race via echocardiography and humoral analysis. Reductions
      in diastolic filling, unrelated to loading or heart rate, following both
      marathons were reproducible within individuals, which may be a function of
      exercise duration. In contrast, exercise-induced cardiac troponin release was
      inconsistent.

PMID- 17222473
TI  - A dual fluorescence flow cytometric analysis of bacterial adherence to mammalian
      host cells.
AB  - Flow cytometry has provided a powerful tool for analyzing bacteria-host cell
      associations. Established approaches have used bacteria, labeled either directly
      with fluorochromes or indirectly with fluorescently conjugated antibodies, to
      detect these associations. Although useful, these techniques are consistently
      unable to include all host cells in the analysis while excluding free, aggregated
      bacteria. This study describes a new flow cytometry method of assessing bacterial
      adherence to host cells based on direct fluorescent labeling of both bacteria and
      host cells. Eukaryotic host cells were labeled with PKH-26, a red fluorescent
      dye, and bacteria were labeled with fluorescein isothiocyanate, a green
      fluorescent dye. The red host cells were gated and the mean green fluorescence
      intensity (MFI) of these red cells was determined. We used MFI values obtained
      from control samples (unlabeled and labeled host cells with unlabeled bacteria)
      to eliminate contributions due to autofluorescence. The final MFI values
      represent fluorescence of host cells resulting from the adherent bacteria.
      Because all red fluorescent cells are analyzed, this method includes all the
      eukaryotic cells for analysis but excludes all free or aggregated bacteria that
      are not bound to target cells.

PMID- 17222474
TI  - A new TaqMan method for the identification of phytoplasmas associated with
      grapevine yellows by real-time PCR assay.
AB  - Three real-time PCR systems for direct detection of phytoplasmas associated to
      Flavescence doree (FD), Bois noir (BN) and aster yellows (AY) diseases were
      developed. TaqMan probes and primers were designed on the 16S ribosomal RNA
      sequences of phytoplasma genome. A further TaqMan assay, targeting a grapevine
      gene encoding for the chloroplast chaperonin 21, was developed in order to check
      the DNA quality and to verify the absence of PCR inhibition. A comparison between
      real-time PCR and conventional nested-PCR methods for phytoplasma detection was
      carried out on several reference samples from grapevine, periwinkle, other host
      plants and insect species. Detection of FD, BN and AY phytoplasma DNA on infected
      specimens was rapid, specific and reproducible. Sensitivity was as high as nested
      PCR assay. The two procedures were then used on about 450 samples collected from
      grapevines showing yellows symptoms. The results showed that real-time PCR
      approach for phytodiagnostic purposes was more advantageous than nested-PCR
      method with regard to rapidity of the assay and reduced risk of sample cross
      contamination. These new protocols represent an improvement of existing
      analytical methods and could be used as a reliable diagnostic procedure in
      certification and control programs.

PMID- 17222475
TI  - A virtual-accelerator-based verification of a Monte Carlo dose calculation
      algorithm for electron beam treatment planning in clinical situations.
AB  - BACKGROUND AND PURPOSE: The introduction of Monte Carlo (MC) techniques for
      treatment planning and also for verification purposes will have considerable
      impact on the radiation therapy planning process. The aim of this work was to use
      a virtual accelerator to study the performance of a MC-based electron dose
      calculation algorithm, implemented in a commercial treatment planning system.
      METHODS: The performance in phantoms containing air and bone as well as in
      patient-specific geometries (thorax wall, nose, parotid gland and spinal cord)
      has been studied. RESULTS: The agreement between the virtual accelerator and the
      MC dose calculation algorithm is generally very good. A gamma-evaluation with
      criteria of 0.03 Gy/3 mm (per Gy at the depth of maximum dose) shows that, even
      for the worst cases, only a small volume of about 1.5% has gamma>1.0. In the
      worst case, with the 0.02 Gy/2 mm criteria, about 92% of the volume receiving
      more than 0.85 Gy per 100 monitor units (MU) has gamma-values <1.0. The
      corresponding value for the volume receiving more than 0.10 Gy/100 MU is about
      98%. For the 18 MeV spinal-cord case, where a 6 x 20 cm2 insert is used, the TPS
      underestimates the dose outside the primary field due to inadequate modelling of
      the insert. CONCLUSION: The possibility of dose calculations in typical patient
      cases makes the virtual accelerator a powerful tool for validation and evaluation
      of dose calculation algorithms present in treatment planning systems.

PMID- 17222476
TI  - Rhyme processing in the brain: an ERP mapping study.
AB  - The event-related potential (ERP) N450 component has been described in rhyme
      detection tasks as a negative response elicited by non-rhyming words in
      comparison to rhyming ones. This response, which peaked around 450 ms over the
      midline and right hemisphere recording sites, has been subsequently suggested to
      start already at approximately 300 ms. Moreover, although, the phonological N450
      has first been linked to the semantic N400 component, its cognitive nature and
      cerebral origin remained debated. In this study, we re-investigated the time
      course of the electrophysiological responses to rhyming and non-rhyming words and
      estimated their cerebral generators using source localization methods. Waveform
      analysis showed that, prior to the N450 response to non-rhyming, a slightly
      earlier negativity characterized the rhyming condition over left fronto-temporal
      electrodes and peaked at approximately 350 ms. The analysis of the ERP map series
      in terms of functional microstates revealed a specific map segment in the rhyming
      condition and another one in the non-rhyming condition. Source localization
      indicated that the rhyming-elicited microstate engaged predominantly left frontal
      and temporal areas while the non rhyming-specific response recruited temporal and
      parietal regions bilaterally. Our results suggest that, similar to the N400
      component that is also induced by mismatch contexts, the N450 might rely on
      temporal generators.

PMID- 17222477
TI  - Sensitivity of the solution of the Elder problem to density, velocity and
      numerical perturbations.
AB  - In this paper the Elder problem is studied with the purpose of evaluating the
      inherent instabilities associated with the numerical solution of this problem.
      Our focus is first on the question of the existence of a unique numerical
      solution for this problem, and second on the grid density and fluid density
      requirements necessary for a unique numerical solution. In particular we have
      investigated the instability issues associated with the numerical solution of the
      Elder problem from the following perspectives: (i) physical instability issues
      associated with density differences; (ii) sensitivity of the numerical solution
      to idealization irregularities; and, (iii) the importance of a precise velocity
      field calculation and the association of this process with the grid density
      levels that is necessary to solve the Elder problem accurately. In the study
      discussed here we have used a finite element Galerkin model we have developed for
      solving density-dependent flow and transport problems, which will be identified
      as TechFlow. In our study, the numerical results of Frolkovic and de Schepper
      [Frolkovic, P. and H. de Schepper, 2001. Numerical modeling of convection
      dominated transport coupled with density-driven flow in porous media, Adv. Water
      Resour., 24, 63-72.] were replicated using the grid density employed in their
      work. We were also successful in duplicating the same result with a less dense
      grid but with more computational effort based on a global velocity estimation
      process we have adopted. Our results indicate that the global velocity estimation
      approach recommended by Yeh [Yeh, G.-T., 1981. On the computation of Darcian
      velocity and mass balance in finite element modelling of groundwater flow, Water
      Resour. Res., 17(5), 1529-1534.] allows the use of less dense grids while
      obtaining the same accuracy that can be achieved with denser grids. We have also
      observed that the regularity of the elements in the discretization of the
      solution domain does make a difference in obtaining a unique stationary solution
      for this problem. The results of our study also indicate that the density
      differences are critical in the solution of the Elder problem and that high
      density differences lead to the physical instability that is inherent with this
      problem. Other than the physical instability associated with the level of density
      differences used in the Elder problem, the following two points should be
      considered in solving the Elder problem in a consistent manner: (i) strict
      attention should be paid to the vertical grid Peclet number in developing the
      criteria for convergent grid selection; and, (ii) with a globally continuous
      velocity calculation stable solutions can be obtained at lower grid densities.

PMID- 17222478
TI  - M-cadherin and beta-catenin participate in differentiation of rat satellite
      cells.
AB  - Cadherins belong to a large family of membrane glycoprotein adhesion receptors
      that mediate homophilic, calcium-dependent cell adhesion. During myogenesis,
      cadherins are involved in initial cell-to-cell recognition; and it has also been
      suggested that they play a role in the initiation of myoblast fusion into
      multinuclear myotubes. One of the members of the cadherin family, M-cadherin, has
      been detected during embryogenesis in myogenic cells of somitic origin and in
      adult muscles. We investigated the distribution and function of M-cadherin and
      beta-catenin during differentiation of myoblasts in primary cultures of rat
      satellite cells. We found that M-cadherin was accumulated at the areas of contact
      between fusing myoblasts and that it colocalized with beta-catenin. Moreover,
      beta-catenin colocalized with actin in pre-fusing myoblasts. We show that
      myoblast differentiation is accompanied by an increase in the amounts of M
      cadherin and beta-catenin both at the mRNA and the protein level. Flow cytometry
      analysis showed that M-cadherin expression was highest in fusing myoblasts. In
      addition, an antibody specific for the extracellular domain of M-cadherin
      inhibited the fusion of cultured myoblasts. These data suggest that regulation of
      the M-cadherin level plays an important role in the differentiation of satellite
      cells and in myoblast fusion in primary cultures.

PMID- 17222479
TI  - Degradation of fibrillar forms of Alzheimer's amyloid beta-peptide by
      macrophages.
AB  - Cultured microglia internalize fibrillar amyloid Abeta (fAbeta) and deliver it to
      lysosomes. Degradation of fAbeta by microglia is incomplete, but macrophages
      degrade fAbeta efficiently. When mannose-6 phosphorylated lysosomal enzymes were
      added to the culture medium of microglia, degradation of fAbeta was increased,
      and the increased degradation was inhibited by excess mannose-6-phosphate, which
      competes for binding and endocytic uptake. This suggests that low activity of one
      or more lysosomal enzymes in the microglia was responsible for the poor
      degradation of fAbeta. To further characterize the degradation of fAbeta in late
      endosomes and lysosomes, we analyzed fAbeta-derived intracellular degradation
      products in macrophages and microglia by mass spectrometry. Fragments with
      truncations in the first 12 N-terminal residues were observed in extracts from
      both cell types. We also analyzed material released by the cells. Microglia
      released mainly intact Abeta1-42, whereas macrophages released a variety of N
      terminal truncated fragments. These results indicate that initial proteolysis
      near the N-terminus is similar in both cell types, but microglia are limited in
      their ability to make further cuts in the fAbeta.

PMID- 17222480
TI  - Hippocampal hypometabolism predicts cognitive decline from normal aging.
AB  - OBJECTIVE: This longitudinal study used FDG-PET imaging to predict and monitor
      cognitive decline from normal aging. METHODS: Seventy-seven 50-80-year-old normal
      (NL) elderly received longitudinal clinical examinations over 6-14 years (561
      person-years, mean per person 7.2 years). All subjects had a baseline FDG-PET
      scan and 55 subjects received follow-up PET exams. Glucose metabolic rates
      (MRglc) in the hippocampus and cortical regions were examined as predictors and
      correlates of clinical decline. RESULTS: Eleven NL subjects developed dementia,
      including six with Alzheimer's disease (AD), and 19 declined to mild cognitive
      impairment (MCI), on average 8 years after the baseline exam. The baseline
      hippocampal MRglc predicted decline from NL to AD (81% accuracy), including two
      post-mortem confirmed cases, from NL to other dementias (77% accuracy), and from
      NL to MCI (71% accuracy). Greater rates of hippocampal and cortical MRglc
      reductions were found in the declining as compared to the non-declining NL.
      CONCLUSIONS: Hippocampal MRglc reductions using FDG-PET during normal aging
      predict cognitive decline years in advance of the clinical diagnosis. Future
      studies are needed to increase preclinical specificity in differentiating
      dementing disorders.

PMID- 17222481
TI  - Physiological correlates of age-related decline in vibrotactile sensitivity.
AB  - The purpose of this study was to describe age-related changes in vibrotactile
      sensitivity in participants of the Baltimore Longitudinal Study of Aging and to
      identify factors that are associated with impairment in vibrotactile sensitivity
      independent of age. Participants (n=523, age: 26-95 years) underwent measurements
      of vibration perception threshold (VPT, 100Hz) under the 2nd metatarsal head,
      glucose tolerance, serum inflammatory markers, nerve conduction parameters,
      movement time and cognition. Univariate and multivariate regression analyses were
      performed to identify factors that predicted VPT independent of age. Structural
      equation modeling was used to describe relationships between these variables. VPT
      was progressively higher with older age. Adjusting for age and height, VPT was
      similar in men and women and the slope of age-related decline was similar in the
      two genders. Age, height, peroneal nerve conduction velocity and peroneal nerve
      amplitude were independent predictors of VPT. Structural equation model
      demonstrated a direct relationship between peripheral nerve function and VPT.
      Height and circulating inflammatory markers may influence age-related decline in
      vibrotactile sensitivity through their negative impacts on peripheral nerve
      function.

PMID- 17222482
TI  - BDNF genotype potentially modifying the association between incident stroke and
      depression.
AB  - OBJECTIVE: To investigate the role of the brain-derived neurotrophic factor
      (BDNF) gene val66met polymorphism in the association between stroke and
      depression. METHOD: Five hundred community residents aged >65 years without
      stroke or depression at baseline were re-evaluated after 2 years. Disability
      (World Health Organization Disability Assessment Schedule, WHODAS II), cognitive
      function (Mini-Mental State Examination, MMSE), and BDNF genotype were also
      measured at baseline. RESULTS: The association between incident stroke and
      depression was strengthened progressively with increasing numbers of met alleles,
      and was only significant in subjects with the met/met genotype after adjustment
      for disability and cognitive function. CONCLUSION: The BDNF val66met polymorphism
      may modify the association between stroke and depression.

PMID- 17222483
TI  - Organoiodine(III) mediated synthesis of 3,9-diaryl- and 3,9-difuryl-bis-1,2,4
      triazolo[4,3-a][4,3-c]pyrimidines as antibacterial agents.
AB  - Nine 3,9-diaryl- and 3,9-difuryl-bis-1,2,4-triazolo[4,3-a][4,3-c]pyrimidines (3a
      i) have been synthesized by the oxidation of bis-2,4-pyrimidinylhydrazones of
      various araldehydes and furfural with 2equiv of iodobenzene diacetate (IBD) in
      dichloromethane and tested in vitro for their antibacterial activity. Three
      compounds, namely 3,9-di-(4'-fluorophenyl)-bis-1,2,4-triazolo[4,3-a][4,3
      c]pyrimidine (3f), 3,9-di-(4'-nitrophenyl)-bis-1,2,4-triazolo[4,3-a][4,3
      c]pyrimidine (3g) and 3,9-di-(5'-nitro-2'-furyl)-bis-1,2,4-triazolo[4,3-a][4,3
      c]pyrimidine (3i), were associated with substantially higher antibacterial
      activity than some commercial antibiotics against Gram-positive bacteria namely
      Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilis; two Gram
      negative bacteria namely Salmonella typhi and Escherichia coli at MIC (minimum
      inhibitory concentration) 10microg/ml.

PMID- 17222484
TI  - 137Cs and 90Sr in live and dead reindeer lichens (genera Cladonia) from the
      "Kraton-3" underground nuclear explosion site.
AB  - The contents of 137Cs and 90Sr have been determined in 29 samples of live and
      dead reindeer lichens (genera Cladonia) collected at the "Kraton-3" underground
      nuclear explosion site (65.9 degrees N 112.3 degrees E, event year--1978) in
      Yakutia, Russia in 2002. The area contamination was within the range of 0.36-700
      and 0.13-770 kBq m(-2) for 137Cs and 90Sr, respectively. The dead organisms were
      on average much more contaminated than the live ones. Vertical fractionation of
      the live lichen carpet demonstrated maximal activity concentrations of both
      radionuclides in the lower older section of the plants, while for the dead
      lichens the maximal activity concentrations of 137Cs were detected in the upper
      part. The vertical distribution of 90Sr was more or less homogeneous in the
      cushions of dead lichens. Elevated levels of 137Cs and 90Sr activity
      concentrations were also detected in the re-establishing young lichens growing
      over the residua of some dead lichens.

PMID- 17222485
TI  - Chlorine-39 in rainfall at a temperate latitude (40 degrees N).
AB  - Rainwater samples were collected and measured for the radioactivity to confirm
      the presence of Chlorine-39 (T1/2=56.2 min) formed by the interaction of cosmic
      ray slow negative muons, mu- with Argon-40 in the lower atmosphere. The presence
      of 39Cl was confirmed by estimating the half-life of a radionuclide present in
      the rainwater ranging from 58 to 63 min and averaging 60.4 min. The
      disintegration rate of this radionuclide varied from 2.1 to 2.7 Bq L(-1) (125-160
      dpm/L) of rainwater and averaged 2.3 Bq L(-1) (140 dpm/L) of rainwater in
      Thessaloniki (40 degrees 38'N, 22 degrees 58'E), Northern Greece. This
      concentration is indicative of mid or temperate latitudes. This is clearly less
      than that reported in the literature, 1.7 Bq L(-1) (100 dpm/L) of rainwater, for
      a southern latitude 31 degrees 54'N, 34 degrees 49'E (Rehovot, Israel), due to
      the latitudinal effect of cosmic radiation.

PMID- 17222486
TI  - Triggering at the distal A2 pulley.
AB  - We report two cases with triggering at the distal end of the A2 pulley. One was
      caused by enlargement of the flexor digitorum profundus (FDP) tendon and the
      other by enlargement of both slips of the flexor digitorum superficialis (FDS)
      tendon. Both were relieved by reduction tenoplasty and short releases, or
      venting, of the distal A2 pulley.

PMID- 17222487
TI  - Extensor digiti minimi damage due to longstanding Kienbock's disease.

PMID- 17222488
TI  - Muscle adaptation patterns of children with a trans-tibial amputation during
      walking.
AB  - BACKGROUND: Many studies have shown that trans-tibial amputation involves
      modifications of resultant muscle patterns during gait. However, these
      experiments did not estimate the contribution of simultaneous agonist and
      antagonist muscle action (co-contraction) during gait tasks. Diminution of co
      contraction could create joint instability and, thus, change joint integrity,
      which is particularly important in the etiology of degenerative diseases, such as
      osteoarthritis, present at the knees of amputated limbs, and particularly in non
      amputated limbs. The purpose of this study was to determine if there is any
      difference in the production of co-contraction about the knee between able-bodied
      children and children with a trans-tibial amputation during gait. METHODS: Six
      children with a trans-tibial amputation vs. six able-bodied children paired for
      gender, age, weight and height participated in this study. Four one-way ANOVAs
      (P<0.05) were used to observe differences in resultant, agonist and antagonist
      moments, power, and co-contraction index during different phases of gait between
      able-bodied children limbs, the amputated and the non-amputated limbs of children
      with trans-tibial amputation. FINDINGS: Children with a trans-tibial amputation
      modified muscle patterns at their amputated limb and produced smaller co
      contraction (P<0.05) during single limb support, for both the non-amputated and
      amputated limbs when compared to able-bodied children. INTERPRETATION: These
      results suggest that children with a trans-tibial amputation altered their muscle
      patterns to perform locomotion. These changes produced a diminution of co
      contraction during single limb support for both the amputated and non-amputated
      limbs and, thus, could create joint instability.

PMID- 17222489
TI  - Stress-reactivity in psychosis: evidence for an affective pathway to psychosis.
AB  - This paper will review a series of studies using the Experience Sampling Method
      that suggest that altered sensitivity to stress is an endophenotype for
      psychosis. The Experience Sampling Method is a structured diary technique
      allowing the assessment of emotional reactivity to stressors occurring in normal
      daily life. Elevated emotional reactivity to stress was found in subjects
      vulnerable to psychosis, suggesting that affective responses to stressors in the
      flow of daily life are an indicator of genetic and/or environmental liability to
      psychosis. Indeed, the small stressors in daily life associated with affective
      responses also predict more intense moment-to-moment variation of subtle positive
      psychotic experiences. Increased emotional reactivity was found to be independent
      from cognitive impairments, and argued to constitute evidence of an affective
      pathway to psychosis that may underlie a more episodic, reactive, good-outcome
      type of psychosis. Evidence for this hypothesis was found in data suggesting that
      the experience of stressful life events and early trauma were associated with
      increased stress-sensitivity, and that women were more likely to display elevated
      stress-reactivity. These findings are discussed in the light of recent biological
      and psychological mechanisms.

PMID- 17222490
TI  - Social anxiety spectrum and diminished positive experiences: theoretical
      synthesis and meta-analysis.
AB  - Until recently, there has been limited recognition that diminished positive
      psychological experiences are important to understanding the nature of social
      anxiety. Meta-analytic techniques were used to evaluate the strength,
      consistency, and construct specificity of relations between the social anxiety
      spectrum with positive affect and curiosity. The social anxiety spectrum had
      significant inverse relations with positive affect (r=-.36; 95% CI: -.31 to -.40)
      and curiosity (r=-.24; 95% CI: -.20 to -.28). Relations between social anxiety
      and positive affect were stronger in studies sampling from clinical populations.
      Specificity findings (e.g., statistically controlling for depressive symptoms and
      disorders) further confirmed negative associations with positive affect (r=-.21;
      95% CI: -.16 to -.26) and curiosity (r=-.21; 95% CI: -.08 to -.32). The
      literature on social rank, self-presentation concerns, self-regulatory resources,
      and experiential avoidance is reviewed and integrated to elaborate a framework of
      how, why, and when social anxiety may be inversely related to positive
      experiences. The specificity of theory and data to social interaction anxiety is
      supported by an examination of existing work on social performance/observation
      fears and other anxiety conditions. Overall, these findings highlight the
      importance of diminished positive psychological experiences in understanding
      excessive social anxiety.

PMID- 17222491
TI  - Changes in estrogen receptors alpha and beta expression in the brain of mice
      exposed prenatally to bisphenol A.
AB  - The expression of ERs alpha and beta and serotonergic neurons were evaluated in
      the brains of mice prenatally exposed to Bisphenol A, a known endocrine
      disrupting chemical (EDc). Bisphenol A was administered orally at a dose of 2ng/g
      body weight on gestinational days 11-17 to pregnant ICR mice. Newborn male
      offspring (Bis-A mice) were evaluated for the immunoreactivity of ERs alpha and
      beta, serotonin, and serotonin transporter positive cells in the dorsal raphe
      nucleus (DRN). The serum testosterone level was also evaluated. In the Bis-A
      mice, the expression of ERs alpha and beta at 5 and 13 weeks was increased
      compared with the controls (P<0.04), but this difference disappeared by the 9th
      week. The serotonin, serotonin transporter, and testosterone level differences
      between two groups did not reach significance. Exposure to bisphenol A may have
      changed the expression of ERs in the brain, but did not directly affect serotonin
      neurons in the DRN.

PMID- 17222492
TI  - Cocaine-induced genital reflexes in paradoxical sleep deprived rats: Indications
      of mediation by serotonin receptors.
AB  - As paradoxical sleep deprivation (PSD) modifies cocaine-induced genital reflexes
      (penile erection [PE] and ejaculation [EJ]) and since cocaine is a serotonin (5
      HT) reuptake inhibitor, we hypothesized that 5-HT also plays a role in these
      genital reflexes in PSD male rats. After a 4-day period of PSD each group was
      administered with serotonergic drugs prior to cocaine and placed in observation
      cages. The selective 5-HT(1) agonist (8-OH-DPAT) completely abolished PE events
      whereas the antagonist (pindolol) did not produce significant effects in the
      number of animals displaying PE. It was found that both drugs reduce the
      frequency of PE. There were no significant effects on the number of animals that
      ejaculated or in its frequency after pindolol although both parameters were
      reduced by the agonist at the highest doses (2 and 4 mg/kg, SC). Pretreatment
      with the 5-HT(2) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI)
      (0.12; 0.5 and 1 mg/kg, SC) significantly reduced the number of rats displaying
      PE and all doses reduced both PE and EJ frequencies. The number of animals
      displaying PE after 5-HT(2) antagonist (ketanserin) pretreatment at 1 and 2.5
      mg/kg doses was significantly decreased in relation to vehicle rats and all doses
      reduced PE frequency. 5-HT(2) compounds at any dose did not affect the number of
      animals ejaculating, but the frequency was significantly reduced by all doses of
      DOI and by 1 to 5 mg/kg doses of ketanserin. Taken together, the results suggest
      that serotonergic receptors play an important role in genital reflexes induced by
      cocaine in sleep deprived males.

PMID- 17222493
TI  - Selective hair analysis of nicotine by molecular imprinted solid-phase
      extraction: an application for evaluating tobacco smoke exposure.
AB  - A method using a molecularly imprinted polymer (MIP) as the selective sorbent for
      solid-phase extraction (SPE) has been developed. Its application to the assay of
      hairy nicotine level among smokers and non-smokers with high-performance liquid
      chromatography (HPLC) and evaluation of exposures to the environmental tobacco
      smoke (ETS) were validated. The MIP was synthesized using nicotine as the
      template molecule and methacrylic acid (MAA) as the functional monomer. This MIP
      SPE method provided inherent selectivity and a sensitive response to nicotine
      with a detection limit of 0.2 ng/ml hair at a signal-to-noise ratio of 3:1 and
      the limit of quantification was 0.5 ng/ml. The linearity was assessed in the
      range of 0.5-80 ng/ml hair, with a coefficient (r(2)) greater than 0.987. The
      amounts of nicotine determined in smokers and non-smokers hair were in the range
      of 5.1-69.5 ng/mg hair and 0.50-9.3 ng/mg hair, respectively. The reported
      measures of ETS exposure were significantly associated with hairy nicotine
      levels. This assay of nicotine in hair using MISPE provided a very selective and
      reliable method for the evaluation of the exposure to tobacco smoke.

PMID- 17222494
TI  - Induction of apoptosis and cell-cycle arrest in human colon cancer cells by
      meclizine.
AB  - Meclizine (MEC), a histamine H1 antagonist, is used for the treatment of motion
      sickness and vertigo. In this study, we demonstrate that MEC dose-dependently
      induced apoptosis in human colon cancer cell lines (COLO 205 and HT 29 cells).
      Results of a DNA ladder assay revealed that DNA ladders appeared with MEC
      treatment in COLO 205 cells at dosage of >50 microM. In addition, the total cell
      number decreased dose-dependently after treatment with MEC in COLO 205 and HT 29
      cells. Using flow cytometry, the percentage of COLO 205 cells arrested at G0/G1
      phase increased dose-dependently. Analysis of changes in cell-cycle arrest
      associated proteins with Western blotting showed that p53 and p21 were
      upregulated after treatment with MEC. The kinase activities of cyclin-dependent
      kinase 2 (CDK2) and CDK4 were suppressed in MEC-treated cells. As for apoptosis,
      MEC may induce upregulation of p53 and downregulation of Bcl-2, thus causing the
      release of cytochrome C from mitochondria and the translocation of apoptosis
      inducing factor (AIF) to the nucleus. This resulted in the activation of caspase
      3, 8, and 9. Our results provide the molecular basis of MEC-induced apoptosis and
      cell-cycle arrest in human colon cancer cells.

PMID- 17222495
TI  - Anandamide-induced Ca2+ elevation leading to p38 MAPK phosphorylation and
      subsequent cell death via apoptosis in human osteosarcoma cells.
AB  - The effect of anandamide on human osteoblasts is unclear. This study examined the
      effect of anandamide on viability, apoptosis, mitogen-activated protein kinases
      (MAPKs) and Ca2+ levels in MG63 osteosarcoma cells. Anandamide at 50-200 microM
      decreased cell viability via apoptosis as demonstrated by propidium iodide
      staining and activation of caspase-3. Immunoblotting suggested that anandamide
      induced expression of ERK, JNK and p38 MAPK. Anandamide-induced cell death and
      apoptosis were reversed by SB203580, but not by PD98059 and SP600125, suggesting
      that anandamide's action was via p38 MAPK, but not via ERK and JNK. Anandamide at
      1-100 microM induced [Ca2+]i increases. Removal of extracellular Ca2+ decreased
      the anandamide response, indicating that anandamide induced Ca2+ influx and Ca2+
      release. Chelation of intracellular Ca2+ with BAPTA reversed anandamide-induced
      cell death and p38 MAPK phosphorylation. Collectively, in MG63 cells, anandamide
      induced [Ca2+]i increases which evoked p38 MAPK phosphorylation. This p38 MAPK
      phosphorylation subsequently activated caspase-3 leading to apoptosis.

PMID- 17222496
TI  - Dose- and time-dependent effects of sulfur mustard on antioxidant system in liver
      and brain of rat.
AB  - This study investigates the dose- and time-dependent effects of sulfur mustard
      (SM) on antioxidant system and lipid peroxidation in liver and brain of rats. For
      this purpose, male Wistar rats were randomly divided into eight groups and
      treated as follows: group 1 as control and groups 2-8 as experimental groups that
      received SM (1-80 mg/kg) through intraperitoneal injection. Rats were killed
      after 2, 7 and 14 days of exposure. SM dose-dependently decreased body weight.
      Superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST)
      activities in liver were significantly increased at SM doses lower than 10 mg/kg
      after 2 and 7 days of exposure. However, the recovery of these parameters was
      observed after 14 days. At these concentrations, no significant change in
      glutathione (GSH) and malondialdehyde (MDA) levels were observed. At doses higher
      than 10 mg/kg, SM significantly decreased SOD, CAT, glutathione peroxidase (GPX),
      and GST activities in liver and brain and decreased glutathione reductase (GR)
      activity in liver, which was associated with a depletion of GSH and increased MDA
      level. Present data indicate that the effect of SM is dose- and time-dependent
      and at higher doses (>10 mg/kg) induces an oxidative stress response by depleting
      the antioxidant defense systems and increasing lipid peroxidation in liver and
      brain of rats.

PMID- 17222497
TI  - Protective effects of echinacoside on carbon tetrachloride-induced hepatotoxicity
      in rats.
AB  - The aim of this study was to investigate the possible protective effects of
      echinacoside, one of the phenylethanoids isolated from the stems of Cistanches
      salsa, a Chinese herbal medicine, on the free radical damage of liver caused by
      carbon tetrachloride in rats. Treatment of rats with carbon tetrachloride
      produced severe liver injury, as demonstrated by dramatic elevation of serum ALT,
      AST levels and typical histopathological changes including hepatocyte necrosis or
      apoptosis, haemorrhage, fatty degeneration, etc. In addition, carbon
      tetrachloride administration caused oxidative stress in rats, as evidenced by
      increased reactive oxygen species (ROS) production and MDA concentrations in the
      liver of rats, along with a remarkable reduction in hepatic SOD activity and GSH
      content. However, simultaneous treatment with echinacoside (50mg/kg,
      intraperitoneally) significantly attenuated carbon tetrachloride-induced
      hepatotoxicity. The results showed that serum ALT, AST levels and hepatic MDA
      content as well as ROS production were reduced dramatically, and hepatic SOD
      activity and GSH content were restored remarkably by echinacoside administration,
      as compared to the carbon tetrachloride-treated rats. Moreover, the
      histopathological damage of liver and the number of apoptotic hepatocytes were
      also significantly ameliorated by echinacoside treatment. It is therefore
      suggested that echinacoside can provide a definite protective effect against
      acute hepatic injury caused by CCl(4) in rats, which may mainly be associated
      with its antioxidative effect.

PMID- 17222498
TI  - The interactions of aurein 1.2 with cancer cell membranes.
AB  - Here, the interactions of aurein 1.2, a defence peptide, with T98G glioblastoma
      cell membranes are studied. The peptide induced maximal surface pressure changes
      of circa 9 mN m(-1) in monolayers of endogenous T98G membrane lipid. Reducing
      monolayer anionic lipid showed a positive correlation (R(2)>0.91) with decreases
      in maximal surface pressure changes induced by aurein 1.2 (circa 3 mN m(-1) in
      the absence of this lipid). Cancer cell membrane invasion by the peptide
      therefore appears not to be mediated by lipid receptors or specific lipid
      requirements but rather a general requirement for anionic lipid and/or other
      negatively charged membrane components.

PMID- 17222499
TI  - Ligand-mediated conformational changes and positioning of tryptophans in
      reconstituted human sodium/D-glucose cotransporter1 (hSGLT1) probed by tryptophan
      fluorescence.
AB  - Recombinant purified human sodium/D-glucose cotransporter1 (hSGLT1) was
      reconstituted in a functional form into phospholipid vesicles and its
      conformational states in the absence and presence of ligands and inhibitors were
      probed by intrinsic tryptophan fluorescence. In the presence of sodium, sugars
      increase intrinsic fluorescence (maximum 17%) in a saturable manner in the
      following order alpha-MDG >D-Glu approximately D-Gal >> D-Man >D-All, with no
      effect of L-Glu. Apparent affinities ranging from 0.65 to 10.4 mM were observed.
      In addition, D-Glu increased the accessibility of the Trps to hydrophilic
      collisional quenchers. On the contrary, the transport inhibitor phlorizin
      decreased Trps fluorescence in a sodium-dependent manner by 50% with a red shift
      of 4-6 nm and decreased quencher accessibility, these effects were saturable with
      a high affinity of 5 microM. Furthermore, the positioning of the tryptophans in
      the reconstituted transporter was investigated. hSGLT1 Trps fluorescence was
      reduced by N-bromosuccinimide treatment maximally 25% in membranes and 65% in
      solution. The fluorescence was also significantly but differently quenched by the
      lipid-soluble spin labeled probes 5-Doxyl-phosphatidylcholine (40%) and 12-Doxyl
      phosphatidylcholine (26%). Depth-calculation using the parallax method suggested
      a location of Trps at an average depth of 10 angstrom from the center of the
      bilayer. These studies demonstrate the existence of different conformational
      states of the membrane-embedded transporter in its glucose-free form, as sodium
      glucose-carrier complex and as sodium-phlorizin-carrier complex. They further
      indicate that most of the Trp residues in hSGLT1 are located in hydrophobic
      regions of the protein or in contact with the lipid bilayer of the membrane.
      There, they are located close to the membrane-water interface contributing to the
      vectorial nature of the transporter.

PMID- 17222500
TI  - Optimal nonpoint source pollution control strategies for a reservoir watershed in
      Taiwan.
AB  - The purpose of this study is to develop a model for optimal nonpoint source
      pollution control for the Fei-Tsui Reservoir watershed in Northern Taiwan.
      Several structural best management practices (BMPs) are selected to treat
      stormwater runoff. The complete model consists of two interacting components: an
      optimization model based on discrete differential dynamic programming (DDDP) and
      a zero-dimensional reservoir water quality model. A predefined procedure is used
      to locate suitable sites for construction of various selected BMPs in the
      watershed. In the optimization model, the objective function is to find the best
      combination of BMP type and placement, which minimizes the total construction and
      operation, maintenance, and repair (OMR) costs of the BMPs. The constraints are
      the water quality standards for total phosphorus (TP) and total suspended solids
      (TSS) concentrations in the reservoir. A zero-dimensional reservoir water quality
      model of the Vollenweider type is embedded in the optimization framework to
      simulate pollutant concentrations in Fei-Tsui Reservoir. The resulting optimal
      cost and benefit of water quality improvement are depicted by the model-derived
      trade-off curves. The modeling framework developed in the present study could be
      used as an efficient tool for planning a watershed-wide implementation of BMPs
      for mitigating stormwater pollution impact on the receiving water bodies.

PMID- 17222501
TI  - The role of granulocytes following intravesical BCG prophylaxis.
AB  - OBJECTIVES: The antitumour effect of bacillus Calmette-Guerin (BCG) still remains
      relatively undefined. Most investigations on its mechanism of action have focused
      on mononuclear cells; little consideration has been given to granulocytes. We
      analysed urine of patients with bladder cancer during 8 wk of intravesical BCG
      prophylaxis. The number of polymorphonuclear neutrophils (PMNs) and urothelial
      cells (UCs) was evaluated. We examined the in vitro response of the T24 UC line
      to human PMNs after BCG treatment. METHODS: Seventeen patients were enrolled in
      the study. Cytologic analyses were performed on urine samples collected before
      each BCG instillation and after 2 h from the first voided urine after BCG
      instillation. Elastase activity was determined on these samples to evaluate PMN
      activation. PMN-induced damage was measured on the T24 cell line treated with
      BCG. RESULTS: After BCG treatment, a large number of PMNs transmigrated through
      the urothelium and PMNs adherent to detached UCs were found. One patient, who did
      not respond with significant PMN transmigration, experienced recurrent disease.
      The number of eosinophils that transmigrated was low, with the exception of three
      patients with recurrent disease. In vitro, PMNs adhered to BCG-primed T24 cells
      and damaged the monolayer. CONCLUSIONS: The results agree with recent evidence
      that PMNs may play an important role in the antitumour action of BCG during the
      BCG induction period. This role is probably nonspecific because both normal UCs
      in vivo and tumour cells in vitro appeared to be injured. As suggested by results
      obtained from a limited number of patients, a high number of eosinophils in the
      urine may indicate therapy failure.

PMID- 17222502
TI  - Pro-opiomelanocortin peptides and the adrenal gland.
AB  - The adrenal gland regulates a number of essential biological functions through
      production of steroids and catecholamines. Pro-opiomelanocortin (POMC)-derived
      peptides have been implicated in all aspects of generating, maintaining, and
      functioning of the adrenal glands. An appreciation for the roles of POMC-derived
      peptides with respect to the adrenal has been gained from experiments in vitro,
      and in vivo in different animal models which surgically, pharmacologically, or
      genetically decrease or increase the amount of POMC peptides available. We
      recently produced a mouse model with a deletion of the entire coding region of
      the POMC gene, thus lacking all POMC-derived peptides, from all sources, and at
      all times. Here we will summarize and discuss the results of traditional in vivo
      studies on the role of POMC peptides in adrenal development, maintenance, and
      function in the context of findings in a mouse model genetically lacking all POMC
      derived peptides.

PMID- 17222503
TI  - Gender and gonadal status differences in zona reticularis expression in marmoset
      monkey adrenals: Cytochrome b5 localization with respect to cytochrome P450 17,20
      lyase activity.
AB  - Neonatal marmosets express an adrenal fetal zone comparable to humans. While
      adult males fail to express a functional ZR, with barely detectable blood DHEA
      levels, females produce higher levels of DHEA than males in adulthood. We
      investigated the presence of a putative functional ZR in adult female marmosets.
      In contrast to males, immunohistochemical analysis showed the ZR marker
      cytochrome b5 was elevated in the innermost zone in cycling females (compared to
      testis-intact males), further elevated in the adrenals from anovulatory females,
      and substantially elevated and continuous in ovariectomized females. As a
      functional test in vivo, following overnight dexamethasone treatment, cycling and
      anovulatory females showed higher levels of DHEA relative to males, but DHEA
      failed to increase in response to ACTH. In direct contrast, while ovariectomized
      females exhibited lower initial DHEA levels, clear increases were detectable
      after ACTH administration (p<0.05), suggesting an adrenal origin. The apparent
      differences in cytochrome b5 expression between groups were also further verified
      by Western blotting of adrenal microsomes, and compared to 17,20-lyase activity;
      the two parameters were positively correlated (p<0.01) across multiple treatment
      groups. We conclude that the cycling female marmoset expresses a rudimentary ZR
      with at least a capacity for DHEA production that becomes significantly ACTH
      responsive after anovulation. Expression of cytochrome b5 in this region may be
      directly or indirectly controlled by gonadal function, and is, at least in part,
      a critical determinant in the development of an adrenal ZR that is more defined
      and significantly ACTH-responsive.

PMID- 17222504
TI  - In search of tumor suppressing functions of menin.
AB  - Human hereditary tumor syndromes serve as an ideal model for studying molecular
      pathways regulating tumorigenesis. Multiple endocrine neoplasia type 1 (MEN1), a
      human familial tumor syndrome, results from mutations in the Men1 gene. Men1
      encodes a novel tumor suppressor, menin, of unknown biochemical function.
      Recently, significant progress has been made in identifying menin as a regulator
      of gene transcription, cell proliferation, apoptosis, and genome stability,
      leading to a new model of understanding menin's tumor-suppressing function. These
      findings suggest that menin's diverse functions depend on its association with
      chromatin and its control over gene transcription. This knowledge will likely be
      translated into new strategies to improve therapeutic interventions against MEN1
      and other related cancers.

PMID- 17222505
TI  - GPR30: A G protein-coupled receptor for estrogen.
AB  - Estrogen is a critical steroid in human physiology exerting its effect both at
      the transcriptional level as well as at the level of rapid intracellular
      signaling through second messengers. Many of estrogen's transcriptional effects
      have long been known to be mediated through classical nuclear steroid receptors
      but recent studies also demonstrate the existence of a 7-transmembrane G protein
      coupled receptor, GPR30 that responds to estrogen with rapid cellular signaling.
      There is currently controversy over the ability of classical estrogen receptors
      to recapitulate GPR30-mediated signaling mechanisms and vice versa. This article
      will summarize recent literature and address the relationship between GPR30 and
      conventional estrogen receptor signaling.

PMID- 17222506
TI  - Congestion of epidural venous plexus secondary to vertebral artery occlusion
      mimicking a herniated cervical disc.
AB  - Vascular abnormalities or dissection of the vertebral artery are rare causes for
      cervical monoradiculopathy. We present the case of a 44-year-old female patient
      with a short history of radiculopathy of the right C5 root with radicular pain
      and a severe motor deficit. CT-imaging showed a hyperdense structure at the C4/C5
      level suggesting a herniated disc. Because of the neurological deficit the
      patient was operated by a dorsal approach. Intraoperatively no herniated disc but
      only a congested epidural venous plexus was found. Postoperative MRI and
      angiography showed occlusion of the vertebral artery from C3 to C6 level probably
      due to dissection. The present case shows that a CT-study suggestive for a
      herniated disc can be misleading. Enlargement of the vertebral artery secondary
      to dissection or occlusion may lead to compression of the venous plexus which
      resembles disc material on CT-scan.

PMID- 17222507
TI  - Determination of Co(II) in water and soil samples using spectrophotometry coupled
      with preconcentration on 4-amino methyl pyridine anchored silica gel column.
AB  - 4-amino methyl pyridine anchored silica gel (4-AMPS) was used as a sorbent in a
      simple sensitive spectrophotometry determination of Co(II) in various samples
      using piperazine dithiocarbamate as a color developing agent (lambda(max)=390 nm)
      at pH 5.0+/-0.2. Beer's law was obeyed over the range of 0.1-5.0 microg ml(-1).
      The molar absorptivity and Sandell's sensitivity were 1.257x10(5) lmol(-1) cm(-1)
      and 0.006145 microg cm(-2), respectively. Under these conditions, the
      preconcentration factor obtained was 80, and the detection limit achieved was 5.0
      ng ml(-1). The detailed study of various interfering ions made the method more
      sensitive and selective. The recovery of Co(II) from various samples range from
      97.50 to 99.66%. The present method was successfully applied for the
      determination of Co(II) in various water and soil samples. The proposed method
      was compared with reported methods in terms of Student's 't'-test and variance
      ratio 'f'-test which indicates that there is no significant difference between
      proposed and literature method at 95% confidence level.

PMID- 17222509
TI  - Freundlich and Langmuir adsorption isotherms and kinetics for the removal of
      Tartrazine from aqueous solutions using hen feathers.
AB  - Tartrazine, a yellow menace, is widely being used in cosmetics, foodstuffs,
      medicines and textile. It is carcinogenic and also catalyzes allergic problems.
      In the present work the ability to remove Tartrazine from aqueous solutions has
      been studied using waste material-hen feathers, as adsorbent. Effects of pH,
      concentration of the dye, temperature and adsorbent dosage have been studied.
      Equilibrium isotherms for the adsorption of the dye were measured experimentally.
      Results were analyzed by the Freundlich and Langmuir equation at different
      temperatures and determined the characteristic parameters for each adsorption
      isotherm. The adsorption process has been found endothermic in nature and
      thermodynamic parameters, Gibb's free energy (DeltaG degrees), change in enthalpy
      (DeltaH degrees) and change in entropy (DeltaS degrees) have been calculated. The
      paper also includes results on the kinetic measurements of adsorption of the dye
      on hen feathers at different temperatures. By rate expression and treatment of
      data it has been established that the adsorption of Tartrazine over hen feathers
      follows a first-order kinetics and a film diffusion mechanism operates at all the
      temperatures.

PMID- 17222508
TI  - Leachability of metals from sludge-based artificial lightweight aggregate.
AB  - Metal sludge from industrial wastewater treatment plants was mixed with mining
      residues to be recycled into lightweight aggregate (LWA) through sintering at
      different temperatures. The physical properties of the LWA thus obtained were
      examined by scanning electron microscopy analyzer (SEM) coupled with an energy
      dispersive X-ray analyzer (EDX). The sequential extraction method combined with
      inductively coupled plasma atomic emission spectrometry (ICP-AES) was employed to
      determine the concentration and distribution of hazardous toxic elements in the
      metal sludge-based artificial LWA. The results show that the leaching
      concentrations of Cd, Cr, Cu, and Pb present in the non-sintered raw aggregate
      pellets reached 7.4, 68.0, 96.0, and 61.4 mg/l, respectively, far exceeding the
      regulatory threshold. Sintering at 1150 degrees C for 15 min results in stronger
      chemical bonds being formed between the elements. Hence, after the first three
      steps of sequential extraction, the concentrations of Cr, Cu, and Pb reached
      2.69, 1.50, and 1.88 mg/l at 1150 degrees C, while the final residues had total
      concentrations of 96.1, 88.4, and 60.6 mg/kg, respectively, with Cd undetected in
      both phases. The concentration levels fell within the regulatory threshold,
      indicating that the LWA fabricated from recycled metal sludge contains elements
      that are toxic and hazardous but not leached. Having no harmful effect on the
      environment, the metal sludge-based artificial LWA is not only safe but also
      practical with good physical properties.

PMID- 17222510
TI  - Electrochemical treatment of paper mill wastewater using three-dimensional
      electrodes with Ti/Co/SnO2-Sb2O5 anode.
AB  - The properties of the interlayer and outer layer of Ti/Co/SnO2-Sb2O5 electrode
      were studied, and the electrochemical behavior was examined as well. As a result
      of unsatisfactory treatment using Ti/Co/SnO2-Sb2O5 electrode, electrochemical
      disposal of paper mill wastewater employing three-dimensional electrodes,
      combining active carbon granules serving as packed bed particle electrodes, with
      Ti/Co/SnO2-Sb2O5 anode, was performed. The outcome demonstrates that efficient
      degradation was achieved. The residual dimensionless chemical oxygen demand (COD)
      concentration reached 0.137, and color removal 75% applying 167 mA cm(-2) current
      density at pH 11 and 15 g l(-1) NaCl. The instant current efficiency, energy
      cost, electrochemical oxidation index (EOI) and kinetic constant of the reaction
      were calculated. At the same time, the influence of pH and current density on COD
      abatement and decolorization was also investigated, respectively.

PMID- 17222511
TI  - Mathematical modeling of copper(II) ion inhibition on COD removal in an activated
      sludge unit.
AB  - A mathematical model was developed to describe the Cu(II) ion inhibition on
      chemical oxygen demand (COD) removal from synthetic wastewater containing 15 mg
      l(-1) Cu(II) in an activated sludge unit. Experimental data obtained at different
      sludge ages (5-30 days) and hydraulic residence times (HRT) (5-25 h) were used to
      determine the kinetic, stoichiometric and inhibition constants for the COD
      removal rate in the presence and absence of Cu(II) ions. The inhibition pattern
      was identified as non-competitive, since Cu(II) ion inhibitions were observed
      both on maximum specific substrate removal rate (k) and on the saturation
      constant (Ks) with the inhibition constants of 97 and 18 mg l(-1), respectively,
      indicating more pronounced inhibition on Ks. The growth yield coefficient (Y)
      decreased and the death rate constant (b) increased in the presence of Cu(II)
      ions due to copper ion toxicity on microbial growth with inhibition constants of
      29 and 200 mg l(-1), respectively indicating more effective inhibition on the
      growth yield coefficient or higher maintenance requirements. The mathematical
      model with the predetermined kinetic constants was able to predict the system
      performance reasonably well especially at high HRT operations.

PMID- 17222512
TI  - A systematic review of the relation between physical capacity and future low back
      and neck/shoulder pain.
AB  - The results of longitudinal studies reporting on the relation between physical
      capacity and the risk of musculoskeletal disorders have never been reviewed in a
      systematic way. The objective of the present systematic review is to investigate
      if there is evidence that low muscle strength, low muscle endurance, or reduced
      spinal mobility are predictors of future low back or neck/shoulder pain.
      Abstracts found by electronic databases were checked on several inclusion
      criteria. Two reviewers separately evaluated the quality of the studies. Based on
      the quality and the consistency of the results of the included studies, three
      levels of evidence were constructed. The results of 26 prospective cohort studies
      were summarized, of which 24 reported on the longitudinal relationship between
      physical capacity measures and the risk of low back pain and only three studies
      reported on the longitudinal relationship between physical capacity measures and
      the risk of neck/shoulder pain. We found strong evidence that there is no
      relationship between trunk muscle endurance and the risk of low back pain.
      Furthermore, due to inconsistent results in multiple studies, we found
      inconclusive evidence for a relationship between trunk muscle strength, or
      mobility of the lumbar spine and the risk of low back pain. Finally, due to a
      limited number of studies, we found inconclusive evidence for a relationship
      between physical capacity measures and the risk of neck/shoulder pain. Due to
      heterogeneity, the results of this systematic review have to be interpreted with
      caution.

PMID- 17222513
TI  - Structure solution with three-dimensional sets of precessed electron diffraction
      intensities.
AB  - The use of the precession technique for obtaining three-dimensional (3D) sets of
      electron diffraction intensities suitable for structure solution is discussed.
      The minerals uvarovite and akermanite have been used as testing structures. The
      electron diffraction data sets obtained on these samples retain an acceptable
      linear relation with calculated structure factor amplitudes. The quality of these
      data is suitable to solve both structures using direct methods opening the
      possibility to use 3D precession ED data for solving unknown mineral structures.

PMID- 17222514
TI  - Palliative care in adolescents.
AB  - The cure rate of cancer in adolescents is high but between 10% and 40% of them
      will develop incurable disease depending on tumor type and prognostic factors.
      These patients will need palliative care defined as supportive care to optimize
      comfort, function and social support of the patient and the family. Palliative
      care should include attention to symptom control, psychosocial and spiritual
      issues and should be given by a multidisciplinary team. Palliative care in
      adolescents should also take care of the specific physical and psychosocial
      developmental changes in this age group. Furthermore, specific spiritual, ethical
      and legal issues have to be taken into account.

PMID- 17222515
TI  - Chronic use of marijuana decreases cannabinoid receptor binding and mRNA
      expression in the human brain.
AB  - Chronic exposure to Cannabis sativa (marijuana) produced a significant down
      regulation of cannabinoid receptor in the postmortem human brain. The significant
      decrease in maximal binding capacity was not accompanied by changes in the
      affinity constant. [3H]SR141716A binding was reduced in the caudate nucleus,
      putamen and in the accumbens nucleus. A significant decrease of binding sites was
      seen in the globus pallidus. Also in the ventral tegmental area and substantia
      nigra pars reticulata quantitative analysis of the density of receptors shows a
      significant reduction in [3H]SR141716A binding. In Cannabis sativa user brains,
      compared with normal brains [3H]SR141716A binding was reduced only in the
      hippocampus. The density of cannabinoid receptor 1 mRNA-positive neurons was
      significantly lower in Cannabis sativa users than in control brains for the
      caudate nucleus, putamen, accumbens nucleus and hippocampal region (CA1-CA4,
      areas of Ammon's horn). No hybridization was seen in the mesencephalon and globus
      pallidus.

PMID- 17222516
TI  - The actin binding domain of ACF7 binds directly to the tetratricopeptide repeat
      domains of rapsyn.
AB  - Formation of the neuromuscular junction requires the release of agrin from the
      presynaptic terminal of motor neurons. Clustering of acetylcholine receptors
      (AChRs) on the postsynaptic sarcolemma is initiated by agrin-dependent activation
      of the muscle-specific kinase. While the postsynaptic scaffolding protein rapsyn
      is vital for high density AChR aggregation, little is known about the mechanism
      through which AChRs are immobilized on the postsynaptic membrane. Ultrastructural
      and immunohistochemical studies of rat skeletal muscle have suggested that AChRs
      are anchored to a membrane-associated cytoskeleton that contains spectrin-like
      proteins and is thus similar to that of the human erythrocyte [Bloch RJ, Bezakova
      G, Ursitti JA, Zhou D, Pumplin DW (1997) A membrane skeleton that clusters
      nicotinic acetylcholine receptors in muscle. Soc Gen Physiol Ser 52:177-195]. We
      are studying a protein of the spectrin superfamily, ACF7 (also known as MACF), as
      a postsynaptic cytoskeletal component of the neuromuscular junction. ACF7 has
      multiple cytoskeleton-binding domains, including an N-terminal actin-binding
      domain that, we postulate, may interact with rapsyn, the scaffolding protein that
      binds directly to AChRs. To test this hypothesis, we co-expressed fragments of
      these molecules in cultured fibroblasts and assessed their co-distribution and
      interaction using confocal microscopy and co-immunoprecipitation. We demonstrate
      that the actin-binding domain of ACF7 specifically interacts with the
      tetratricopeptide repeat domains of rapsyn. Furthermore, we show using surface
      plasmon resonance and blot overlay that the actin-binding domain of ACF7 binds
      directly to rapsyn. These results suggest that, in mammalian skeletal muscle,
      AChRs are immobilized in the membrane through rapsyn-mediated anchoring to an
      ACF7-containing network that in turn is linked to the actin cytoskeleton.

PMID- 17222517
TI  - Both long and brief maternal separation produces persistent changes in tissue
      levels of brain monoamines in middle-aged female rats.
AB  - Adverse experiences early in life are associated with an increased incidence of
      later psychopathology including depression. Based on evidence that dysfunction of
      central monoaminergic systems is involved in the pathophysiology of depression,
      we hypothesize that early adversity could negatively affect these systems. To
      test this we have investigated the effects of maternal separation, which has been
      suggested to model early-life stress and the development of a depression-like
      syndrome in the rat, on brain monoaminergic systems. Since depression is more
      common in women and the risk of developing this disorder appears to increase with
      age, we have studied such effects in middle-aged female rats. Rat pups were
      separated for 180 min (long maternal separation; LMS) or 15 min (brief maternal
      separation; BMS, often referred to as neonatal handling) twice daily for 2 weeks
      postpartum. An animal facility-reared (AFR) group was also included. At 15 months
      of age tissue levels of monoamines and their metabolites in several different
      brain regions were analyzed. In the LMS females tissue levels of both 5-HT and 5
      hydroxyindole acetic acid (5-HIAA) were significantly increased in the dorsal
      raphe nucleus, and 5-HIAA and homovanillic acid levels were also elevated in the
      nucleus accumbens as compared with AFR and BMS rats. In the cingulate cortex both
      LMS and BMS decreased noradrenaline (NA) levels, although this effect was more
      pronounced in the LMS rats. On the other hand, BMS decreased 5-HT, 5-HIAA,
      dopamine (DA) as well as NA levels in the amygdala and produced an increase in DA
      levels in response to acute stress in the hypothalamus, an effect not seen in AFR
      rats. Our results demonstrate that LMS produced persistent alterations in both
      serotonergic, noradrenergic and dopaminergic systems in brain regions that have
      been suggested to be implicated in the pathophysiology of depression. In
      addition, BMS affected brain monoaminergic levels mainly in the amygdala.

PMID- 17222518
TI  - Chronic membrane depolarization-induced morphological alteration of developing
      neurons.
AB  - During development of CNS, young neurons experience various stimuli, and
      thereafter differentiate to mature neurons in an activity-dependent manner.
      Membrane depolarization acts as an inducer of excitability and various signals in
      the neurons, which can be used as a model of neuronal activity. However, the
      mechanisms of the influence of membrane depolarization on neuronal
      differentiation have not been fully understood. Therefore, we investigated the
      effect of membrane depolarization on morphology of spines and generation of valid
      electrical activity. Using rat hippocampal cultures treated from the plating day
      with or without high KCl (35 mM, termed HK), we directly observed living neurons
      transfected with green fluorescence protein-expressing plasmid through a two
      photon laser scanning confocal microscope and electrophysiological recording
      using a patch-clamp technique. Compared with controls, the neurons cultured with
      HK for 3 days in vitro (DIV) showed marked filopodia-like protrusions as well as
      an increase in the number of spines, but those cultured with HK for 6 DIV
      profoundly lost these spines, resulting in a small number of fine filopodia-like
      protrusions proximally and on the cell body, and a smooth surface of distal
      dendrites. Electrophysiological recordings showed no spontaneous responses in 6
      DIV HK-treated neurons. Moreover, addition of an N-methyl-D-aspartate receptor
      (NMDAR) antagonist to HK-treated neurons blocked the shrinkage and decrease in
      the number of filopodia-like protrusions significantly. These findings suggest
      that membrane depolarization of developing neurons induces synaptogenesis in the
      early stages of development but chronic treatment with HK causes pathological
      changes through NMDAR, and that there may be alternative mechanisms for the
      physiological differentiation of neurons in later developmental stages.

PMID- 17222519
TI  - Is any link between inflammation and coronary artery ectasia?
AB  - Coronary artery ectasia (CAE) is well-recognized, angiographic finding of
      abnormal coronary dilatation, and detected in 0.3-5.3% of angiographic studies.
      The gold standard for diagnosis this type of aneurysm is coronary angiography,
      which provides information about the size, sample, location and number of
      aneurysms. Despite growing prevalence in recent years, controversy still exists
      as to the pathogenetic mechanisms that underlie this entity. An increased
      incidence of CAE has been reported in several disorders. Examples include
      atherosclerotic vascular disease, heterozygous familial hypercholesterolemia,
      usage of substances including herbicide spray, acetylcholinesterase inhibitors
      and nitrates, previous arterial balloon angioplasty, polyarteritis nodosa and
      Kawasaki syndrome. In addition, possible factors contributing to CAE are
      imbalance between matrix metalloproteinase and tissue inhibitor of
      metalloproteinase, angiotensin converting enzyme genotype, elevated homocysteine
      levels, cocaine user, smoking, vascular trauma, nitrate use and diabetes.
      Emerging investigations have pinpointed inflammation as a central process in all
      stages of atherosclerosis. This inflammatory process culminates in acute
      thrombotic complications and clinical events, which is involved in different
      clinical settings of atherosclerotic diseases. Recent data have also showed that
      CAE is associated with inflammatory response presented as elevated inflammatory
      cytokines and C-reactive protein. Accordingly, more complete understanding of the
      pro- and anti-inflammatory circuits that operate during CAE in particular may
      foster the development of novel therapeutic approaches.

PMID- 17222520
TI  - Some new psychological side effects due to anti-androgenic properties of
      cyproterone compound.

PMID- 17222521
TI  - Oltipraz may be useful in the prevention or treatment of Alzheimer's disease.

PMID- 17222522
TI  - Analysis of the exon-intron structures of fish, amphibian, bird and mammalian
      hatching enzyme genes, with special reference to the intron loss evolution of
      hatching enzyme genes in Teleostei.
AB  - Using gene cloning and in silico cloning, we analyzed the structures of hatching
      enzyme gene orthologs of vertebrates. Comparison led to a hypothesis that
      hatching enzyme genes of Japanese eel conserve an ancestral structure of the
      genes of fishes, amphibians, birds and mammals. However, the exon-intron
      structure of the genes was different from species to species in Teleostei:
      Japanese eel hatching enzyme genes were 9-exon-8-intron genes, and zebrafish
      genes were 5-exon-4-intron genes. In the present study, we further analyzed the
      gene structures of fishes belonging to Acanthopterygii. In the species of
      Teleostei we examined, diversification of hatching enzyme gene into two
      paralogous genes for HCE (high choriolytic enzyme) and LCE (low choriolytic
      enzyme) was found only in the acanthopterygian fishes such as medaka Oryzias
      latipes, Fundulus heteroclitus, Takifugu rubripes and Tetraodon nigroviridis. In
      addition, the HCE gene had no intron, while the LCE gene consisted of 8 exons and
      7 introns. Phylogenetic analysis revealed that HCE and LCE genes were paralogous
      to each other, and diverged during the evolutionary lineage to Acanthopterygii.
      Analysis of gene synteny and cluster structure showed that the syntenic genes
      around the HCE and LCE genes were highly conserved between medaka and Teraodon,
      but such synteny was not found around the zebrafish hatching enzyme genes. We
      hypothesize that the zebrafish hatching enzyme genes were translocated from
      chromosome to chromosome, and lost some of their introns during evolution.

PMID- 17222523
TI  - Lipid vesicles for skin delivery of drugs: reviewing three decades of research.
AB  - Since liposomes were first shown to be of potential value for topical therapy by
      Mezei and Gulasekharam in 1980, studies continued towards further investigation
      and development of lipid vesicles as carriers for skin delivery of drugs. Despite
      this long history of intensive research, lipid vesicles are still considered as a
      controversial class of dermal and transdermal carriers. Accordingly, this article
      provides an overview of the development of lipid vesicles for skin delivery of
      drugs, with special emphasis on recent advances in this field, including the
      development of deformable liposomes and ethosomes.

PMID- 17222524
TI  - Oxidative stress pathways in the potentiation of noise-induced hearing loss by
      acrylonitrile.
AB  - We hypothesize that the disruption of antioxidant defenses is a key mechanism
      whereby chemical contaminants can potentiate noise-induced hearing loss (NIHL).
      This hypothesis was tested using acrylonitrile (ACN), a widely used industrial
      chemical whose metabolism is associated with glutathione (GSH) depletion and
      cyanide (CN) generation. CN, in turn, can inhibit Cu/Zn superoxide dismutase
      (SOD). We have shown previously that ACN potentiates NIHL, even with noise
      exposure approaching permissible occupational levels. However, the relative
      involvement of GSH depletion and/or CN production in this potentiation is still
      unknown. In this study, we altered these metabolic pathways pharmacologically in
      order to further delineate the role of specific antioxidants in the protection of
      the cochlea. We investigated the effects of sodium thiosulfate (STS), a CN
      inhibitor, 4-methylpyrazole (4MP), a drug that blocks CN generation by competing
      with CYP2E1, and l-N-acetylcysteine (l-NAC), a pro-GSH drug, in order to
      distinguish between GSH depletion and CN production as the mechanism responsible
      for potentiation of NIHL by ACN. Long-Evans rats were exposed to an octave-band
      noise (97 dB SPL, 4h/day, 5 days) and ACN (50 mg/kg). Separate pre-treatments
      with STS (150 mg/kg), 4MP (100 mg/kg) and l-NAC (4 x 400 mg/kg) all dramatically
      reduced blood CN levels, but only l-NAC significantly protected GSH levels in
      both the liver and the cochlea. Concurrently, only l-NAC treatment decreased the
      auditory loss and hair cell loss resulting from ACN + noise, suggesting that GSH
      is involved in the protection of the cochlea against reactive oxygen species
      generated by moderate noise levels. On the other hand, CN does not seem to be
      involved in this potentiation.

PMID- 17222525
TI  - A case report of myasthenia gravis localized to the larynx.
AB  - This report describes a very rare case of myasthenia gravis (MG) localized to the
      larynx, with the onset of dyspnea requiring tracheotomy. The vocal cords of this
      patient were fixed in the paramedian position. Under fiberscopic observation,
      improvement of laryngeal function was demonstrated after intravenous injection of
      edrophonium. However, no voice change occurred. The posterior crico-arytenoid
      muscle has the sole responsibility of abducting the vocal cord; thus, it is
      concluded that the dyspnea was caused by the selective paralysis of this muscle.
      We suggest that MG should be considered in cases of vocal cord paralysis of
      unknown etiology.

PMID- 17222526
TI  - Biotechnological approaches for the production of polyhydroxyalkanoates in
      microorganisms and plants - a review.
AB  - The increasing effect of non-degradable plastic wastes is a growing concern.
      Polyhydroxyalkanoates (PHAs), macromolecule-polyesters naturally produced by many
      species of microorganisms, are being considered as a replacement for conventional
      plastics. Unlike petroleum-derived plastics that take several decades to degrade,
      PHAs can be completely bio-degraded within a year by a variety of microorganisms.
      This biodegradation results in carbon dioxide and water, which return to the
      environment. Attempts based on various methods have been undertaken for mass
      production of PHAs. Promising strategies involve genetic engineering of
      microorganisms and plants to introduce production pathways. This challenge
      requires the expression of several genes along with optimization of PHA synthesis
      in the host. Although excellent progress has been made in recombinant hosts, the
      barriers to obtaining high quantities of PHA at low cost still remain to be
      solved. The commercially viable production of PHA in crops, however, appears to
      be a realistic goal for the future.

PMID- 17222527
TI  - Protective effect of ferulic acid on nicotine-induced DNA damage and cellular
      changes in cultured rat peripheral blood lymphocytes: a comparison with N
      acetylcysteine.
AB  - Nicotine is the major pharmacologically active substance in cigarette smoke and
      plays an important etiological role in the development of lung cancer. Incidence
      of cancer may be related to oxidative damage to host genome by nicotine. These
      oxidative actions may be modified by the phytochemicals present in food. The
      present study describes the protective effect of ferulic acid (FA), a naturally
      occurring nutritional compound on nicotine-induced DNA damage and cellular
      changes in cultured rat peripheral blood lymphocytes in comparison with N
      acetylcysteine (NAC), a well-known antioxidant. One-hour exposure of lymphocytes
      to nicotine at the doses of 0.125, 0.25, 0.5, 1, 2, 3 and 4 mM induced a
      statistically significant dose-dependent increase in the levels of thiobarbituric
      acid reactive substances (TBARS), a lipid peroxidative marker and decrease in the
      levels of reduced glutathione (GSH), an important endogenous antioxidant. The
      lowest concentration eliciting significant damage was 1 mM nicotine and maximum
      damage was observed with 3 mM concentration. Hence, the test concentration was
      fixed at 3 mM nicotine. We have used 5 different doses of FA (10, 50, 100, 150
      and 300 microM) and NAC (0.25, 0.5, 1, 2 and 4 mM) to test their protective
      effects. In all the groups, FA and NAC showed a dose-dependent inhibitory effect.
      Maximum protection was observed at the dose of 150 microM FA and 1mM NAC. So, 150
      microM FA and 1mM NAC were used for further studies. There was a significant
      increase in the levels of lipid peroxidative index (TBARS and hydroperoxides
      (HP)), severity of DNA damage (evaluated by comet assay) in nicotine-treated
      group, which were significantly decreased in FA and NAC-treated groups. Nicotine
      treatment significantly decreased the endogenous antioxidant status viz.,
      superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), GSH,
      vitamin A, E and C. Co-administration of FA and NAC to nicotine-treated
      lymphocytes showed a significant increase in the antioxidant status. The
      protective effect of FA was merely equal to that of NAC effect. FA and NAC
      treatment alone did not produce any toxicity to the normal lymphocytes at their
      effective doses. On the whole, there is overwhelming evidence that FA has the
      ability to modulate DNA damage and a variety of cellular changes that occur
      during nicotine-induced toxicity in rat peripheral blood lymphocytes.

PMID- 17222528
TI  - A combined computational and experimental analysis of two families of snoRNA
      genes from Caenorhabditis elegans, revealing the expression and evolution pattern
      of snoRNAs in nematodes.
AB  - Small nucleolar RNAs (snoRNAs) are an abundant group of noncoding RNAs mainly
      involved in the posttranscriptional modifications of rRNAs in eukaryotes. Prior
      to this study, only 28 snoRNA genes had been identified from Caenorhabditis
      elegans, indicating that most snoRNA genes are hidden in the worm genome, which
      represents a simple multicellular metazoan. In this study, a genome-wide analysis
      of the two major families of snoRNA genes in C. elegans was performed using the
      snoscan and snoGPS programs incorporating comparative genome analyses. Seventy
      gene variants, including 36 box C/D and 34 box H/ACA snoRNA genes, were
      identified, of which 50 are novel. Two families of snoRNAs showed a
      characteristic genomic organization. Notably, 6 box C/D snoRNA genes were located
      in the antisense orientation of introns. In contrast to insect and mammal, the
      distances between many intronic snoRNAs and 3' splice sites of introns were less
      than 50 nt in the worm, an unexpected finding as intron-encoded snoRNAs in C.
      elegans are supposed to be expressed in a splicing-dependent pathway.
      Interestingly, a canonical H/ACA snoRNA, PsiCeU5-48, was revealed to be partially
      homologous to small Cajal body-specific RNA (scaRNA) U85 and U89 in fly and
      human, indicating a possible evolutionary relationship between snoRNAs and
      scaRNAs.

PMID- 17222529
TI  - Satellite glial cells in sensory ganglia: their possible contribution to
      inflammatory pain.
AB  - Neurons in dorsal root ganglia (DRG) are surrounded by an envelope of satellite
      glial cells (SGCs). Little is known about SGC physiology and their interactions
      with neurons. In this work, we investigated changes in mouse DRG neurons and SGC
      following the induction of inflammation in the hind paw by the injection of
      complete Freund's adjuvant (CFA). The electrophysiological properties of neurons
      were characterized by intracellular electrodes. Changes in coupling mediated by
      gap junctions between SGCs were monitored using intracellular injection of the
      fluorescent dye Lucifer yellow. Pain was assessed with von Frey hairs. We found
      that two weeks after CFA injection there was a 38% decrease in the threshold for
      firing an action potential in DRG neurons, consistent with neuronal
      hyperexcitability. Injection of Lucifer yellow into SGCs revealed that, compared
      with controls, coupling by gap junctions among SGCs surrounding adjacent neurons
      increased 2.7-, 3.2-, and 2.5-fold one week, two weeks, and one month,
      respectively, after CFA injection. In SGCs enveloping neurons that project into
      the inflamed paw this effect was more enhanced (5.4-fold). Interneuronal coupling
      was augmented by up to 7% after CFA injection. Pain threshold in the injected paw
      decreased by 13%, 16%, and 11% compared with controls at one week, two weeks, and
      one month, respectively, after CFA injection. Intraperitoneal injection of the
      gap junction blocker carbenoxolone prevented the inflammation-induced decrease in
      pain threshold. The results show that augmented glial coupling is one of the
      major events occurring in DRG following inflammation. The elevation in pain
      threshold after carbenoxolone administration provides indirect support for the
      idea that augmented intercellular coupling might contribute to chronic pain.

PMID- 17222530
TI  - Interleukin-1 signaling modulates stress-induced analgesia.
AB  - Exposure to stressful stimuli is often accompanied by reduced pain sensitivity,
      termed "stress-induced analgesia" (SIA). In the present study, the hypothesis
      that interleukin-1 (IL-1) may play a modulatory role in SIA was examined. Two
      genetic mouse models impaired in IL-1-signaling and their wild-type (WT) controls
      were employed. Another group of C57 mice was acutely administered with IL-1
      receptor antagonist (IL-1ra). Mice were exposed to 2min swim stress at one of
      three water temperatures: 32 degrees C (mild stress), 20-23 degrees C (moderate
      stress), or 15 degrees C (severe stress); and then tested for pain sensitivity
      using the hot-plate test. Corticosterone levels were assessed in separate groups
      of WT and mutant mice following exposure to the three types of stress. Mild
      stress induced significant analgesia in the two WT strains and saline-treated
      mice, but not in the mutant strains or the IL-1ra-treated mice. Similarly, mild
      stress induced significantly elevated corticosterone levels in WT mice, and
      blunted corticosterone response in mutant mice. In contrast, both WT and mutant
      strains, as well as IL-1ra-treated mice, displayed analgesic and corticosterone
      responses following moderate and severe stress. Interestingly, the analgesic
      response to moderate stress was markedly potentiated in the mutant strains, as
      compared with their WT controls. The present results support our previous
      findings that in the absence of IL-1, stress response to mild stress is
      noticeably diminished. However, the analgesic response to moderate stress is
      markedly potentiated in mice with impaired IL-1 signaling, corroborating the anti
      analgesic role of IL-1 in several pain modulatory conditions, including SIA.

PMID- 17222531
TI  - Lactational exposure to inorganic mercury: evidence of neurotoxic effects.
AB  - This study examined the effects of inorganic mercury (mercuric chloride - HgCl2)
      exposure exclusively through maternal milk on biochemical parameters related to
      oxidative stress (glutathione and thiobarbituric acid reactive substances levels,
      glutathione peroxidase and glutathione reductase activities) in the cerebellum of
      weanling mice. These parameters were also evaluated in the cerebellum of mothers,
      which were subjected to intraperitoneal injections of HgCl2 (0, 0.5 and 1.5
      mg/kg, once a day) during the lactational period. Considering the relationship
      between cerebellar function and motor activity, the presence of motor impairment
      was also evaluated in the offspring exposed to HgCl2 during lactation. After
      treatments (at weaning), pups lactationally exposed to inorganic mercury showed
      high levels of mercury in the cerebellar tissue, as well as significant
      impairment in motor performance in the rotarod task and decreased locomotor
      activity in the open field. Offspring and dams did not show changes in cerebellar
      glutathione levels or glutathione peroxidase activity. In pups, lactational
      exposure to inorganic mercury significantly increased cerebellar
      lipoperoxidation, as well as the activity of cerebellar glutathione reductase.
      However, these phenomena were not observed in dams. These results indicate that
      inorganic mercury exposure through maternal milk is capable of inducing
      biochemical changes in the cerebellum of weanling mice, as well as motor deficit
      and these phenomena appear to be related to the pro-oxidative properties of
      inorganic mercury.

PMID- 17222533
TI  - Space, time and learning in the hippocampus: how fine spatial and temporal scales
      are expanded into population codes for behavioral control.
AB  - The hippocampus participates in multiple functions, including spatial navigation,
      adaptive timing and declarative (notably, episodic) memory. How does it carry out
      these particular functions? The present article proposes that hippocampal spatial
      and temporal processing are carried out by parallel circuits within entorhinal
      cortex, dentate gyrus and CA3 that are variations of the same circuit design. In
      particular, interactions between these brain regions transform fine spatial and
      temporal scales into population codes that are capable of representing the much
      larger spatial and temporal scales that are needed to control adaptive behaviors.
      Previous models of adaptively timed learning propose how a spectrum of cells
      tuned to brief but different delays are combined and modulated by learning to
      create a population code for controlling goal-oriented behaviors that span
      hundreds of milliseconds or even seconds. Here it is proposed how projections
      from entorhinal grid cells can undergo a similar learning process to create
      hippocampal place cells that can cover a space of many meters that are needed to
      control navigational behaviors. The suggested homology between spatial and
      temporal processing may clarify how spatial and temporal information may be
      integrated into an episodic memory. The model proposes how a path integration
      process activates a spatial map of grid cells. Path integration has a limited
      spatial capacity, and must be reset periodically, leading to the observed grid
      cell periodicity. Integration-to-map transformations have been proposed to exist
      in other brain systems. These include cortical mechanisms for numerical
      representation in the parietal cortex. As in the grid-to-place cell spatial
      expansion, the analog representation of number is extended by additional
      mechanisms to represent much larger numbers. The model also suggests how visual
      landmarks may influence grid cell activities via feedback projections from
      hippocampal place cells to the entorhinal cortex.

PMID- 17222532
TI  - Assessment of adolescent neurotoxicity: rationale and methodological
      considerations.
AB  - This introduction to the special issue of Neurotoxicology and Teratology on "Risk
      of neurobehavioral toxicity in adolescence" begins by broadly considering the
      ontogeny and phylogeny of adolescence, and the potential value of animal models
      of adolescence. Major findings from the emerging neuroscience of adolescence are
      then highlighted to establish the importance of studies of adolescent
      neurotoxicity. A variety of methodological issues that are of particular
      relevance to adolescent exposures are then discussed. These include consideration
      of pharmacokinetic factors, inclusion of other-aged comparison group(s), and
      issues involving timing, route of administration, and exposure-induced
      alterations in growth rate. Despite such methodological challenges, research to
      determine whether adolescence is a time of increased vulnerability (or greater
      resiliency) to specific drugs and environmental toxicants is progressing rapidly,
      as exemplified by the work presented in the articles of this special issue.

PMID- 17222535
TI  - Long-term follow up on recurrence of 305 ameloblastoma cases.
AB  - The aim of this study was to determine the appropriate treatment for
      ameloblastoma by considering the factors associated with recurrence, and to make
      a quantitative prediction of the risk factors for recurrence. Data on age and
      gender distribution, location of the tumour, histopathological findings,
      treatment method, and whether or not patients had a preoperative biopsy
      confirmation report were collected in 305 cases (239 patients; M: 139, F: 100) of
      ameloblastoma diagnosed and treated in 1985-2002. After initial statistical
      evaluation (chi(2)-test and Fisher's exact test), logistic regression analysis
      was performed to check relative significance and predict recurrence. The disease
      free survival function curves of the patients with or without recurrence were
      obtained by the Kaplan-Meier method and compared using univariate regression
      analysis. The correlation between recurrence and the treatment method or
      histopathological type was significant. The differences between the
      'conservative' and 'resection with bone margin' and between the 'conservative'
      and 'segmental resection or maxillectomy' groups in terms of disease-free
      survival were highly significant. The difference between the 'resection with bone
      margin' and 'segmental resection or maxillectomy' groups was not significant. A
      resection with safety margin is the best method to treat most proven
      ameloblastomas, and conservative treatment is reasonable for patients in their
      first decade or with unicystic or plexiform ameloblastoma.

PMID- 17222534
TI  - T cell targeting and phagocytosis of apoptotic biliary epithelial cells in
      primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is characterized by loss of tolerance against
      ubiquitously expressed mitochondrial autoantigens followed by biliary and
      salivary gland epithelial cell (BEC and SGEC) destruction by autoreactive T
      cells. It is unclear why BECs and SGECs are targeted. Previous work demonstrated
      that the reduced form of the major PBC autoantigen predominated in apoptotic BECs
      and SGECs as opposed to an oxidized form in other apoptotic cells. This led to
      the hypothesis that presentation of novel self-peptides from phagocytosed
      apoptotic BECs might contribute to BEC targeting by autoreactive T cells. The
      effect of autoantigen redox status on self-peptide formation was examined along
      with the phagocytic ability of BECs. Oxidation of PBC autoantigens first was
      shown to be due to protein S-glutathionylation of lipoyllysine residues. Absence
      of protein S-glutathionylation generated novel self-peptides and affected T cell
      recognition of a lipoyllysine containing peptide. Liver biopsy staining revealed
      BEC phagocytosis of apoptotic BECs (3.74+/-2.90% of BEC) was present in PBC (7 of
      7 cases) but not in normal livers (0 of 3). BECs have the ability to present
      novel mitochondrial self-peptides derived from phagocytosed apoptotic BECs.
      Apoptotic cell phagocytosis by non-professional phagocytes may influence the
      tissue specificity of autoimmune diseases.

PMID- 17222536
TI  - The effect of prior radiation therapy for treatment of nasopharyngeal cancer on
      wound healing following extractions: incidence of complications and risk factors.
AB  - This is a prospective study of wound healing after extractions in patients who
      had radiation therapy for nasopharyngeal cancer. From 40 patients who fulfilled
      all the study criteria were extracted a total of 155 teeth. The demographic data
      were analysed, checking for factors that might affect the healing process after
      extraction. Wound healing was divided into three groups: normal wound healing,
      delayed healing and osteoradionecrosis. Logistic regression was used to analyse
      possible relationships. There was a low complication rate: 5.8% and 1.9% of
      extractions showed delayed healing and osteoradionecrosis, respectively. The age
      of the patient at time of extraction was the only significant factor that
      influenced the occurrence of delayed healing. It was observed that localized
      radiation absorption was considerably different from the total radiation dose. In
      conclusion, postradiation extractions have a low risk of complications and the
      results point to age as a factor that may influence wound healing.

PMID- 17222537
TI  - Plasma cortisol-dehydroepiandrosterone (DHEA) ratios in schizophrenia and bipolar
      disorder.
AB  - Hypercortisolaemia is a feature of many severe psychiatric illnesses and has been
      suggested to be both a causal and exacerbating factor of clinical symptoms and
      neurocognitive impairment. The adrenal steroid dehydroepiandrosterone (DHEA) has
      antiglucocorticoid properties that may have regulatory effects on glucocorticoid
      action in the brain. However, there is a paucity of data on these steroids and
      their ratio in schizophrenia and bipolar disorder. We therefore sought to assess
      cortisol and DHEA levels and the cortisol-DHEA ratio in patients with
      schizophrenia (n=20) and bipolar disorder (n=20), on stable medication for a
      minimum of 6 weeks, and healthy age- and sex-matched control subjects (n=20).
      Steroid levels were measured from plasma samples collected at 30 min intervals
      from 1:00 p.m. to 4:00 p.m. Cortisol levels were found to be significantly
      elevated in both patient groups compared with controls. DHEA levels were elevated
      in schizophrenic patients compared with bipolar patients and controls, but there
      was no evidence of a difference in the cortisol-DHEA ratio of the groups. These
      data suggest that afternoon hypercortisolaemia is evident in symptomatic bipolar
      and schizophrenic patients compared to controls. However, an elevation in DHEA
      levels may represent a specific endocrine marker in schizophrenia.

PMID- 17222538
TI  - Compliance with medication but not structural MRI measures predict functional
      outcome in first-episode schizophrenia patients.

PMID- 17222539
TI  - Functional disconnections in the direct and indirect amygdala pathways for fear
      processing in schizophrenia.
AB  - BACKGROUND: Schizophrenia patients show reduced neural activity, relative to
      controls, in the amygdala and its projection to the medial prefrontal cortex
      (MPFC) in response to fear perception. In this study we tested the hypothesis
      that schizophrenia is characterized by abnormal functional connectivity in the
      amygdala network underlying fear perception. METHODS: Functional MRI images were
      acquired from 14 schizophrenia patients and 14 matched healthy control subjects
      during an emotion perception task, in which fearful and neutral facial expression
      stimuli were presented pseudorandomly under nonconscious (using masking) and
      conscious conditions. Both subtraction and functional connectivity analyses were
      undertaken using a region of interest approach. RESULTS: In response to fearful
      facial expressions, schizophrenia patients displayed reduced amygdala activity,
      compared to controls, in both the conscious and nonconscious conditions. The
      amygdala displayed a reversal of the normal pattern of connectivity with the
      brainstem, visual cortex, and also with the dorsal and ventral divisions of the
      MPFC in the schizophrenia patients. CONCLUSIONS: The presence of functional
      disconnections in amygdala pathways suggests that schizophrenia patients have a
      failure in coordinating their automatic orienting to salient signals and the
      associated prefrontal monitoring of these signals.

PMID- 17222540
TI  - [New challenges in therapeutic management of human immunodeficiency virus
      infected children].
AB  - More than 2 millions of children worldwide are HIV-infected. Recently, the HIV
      related mortality and morbidity has dramatically decreased due to the use of
      antiretroviral multitherapies in the HIV-infected children. However the
      therapeutic management of HIV-infected children is complex and may be complicated
      by socio-familial issues. Short and long term toxicity of antiretrovirals but
      also of HIV itself are of concern. Despite the good clinical and immunological
      results of antiretroviral multitherapies, virological failure may occur.
      Paediatric pharmacokinetic specificities and inadequate galenic presentation of
      drugs could lead to virological failure. However, the use of more potent drugs
      with more adapted presentation actually reduces this risk of failure. Prospective
      cohorts of HIV-infected children and new antiretroviral drugs paediatric
      evaluation are of key importance and can improve the paediatric therapeutic
      management. Finally, universal access to antiretroviral drugs in children,
      particularly in developing countries is the major actual and future challenge.

PMID- 17222541
TI  - Changes in the ciliate assemblage along a fluvial system related to physical,
      chemical and geomorphological characteristics.
AB  - Samples were collected monthly from the water-sediment interface at six stations
      along the Mincio River (northern Italy) during a 1-year study of the ciliated
      protozoan communities. Four stations were located upstream of the Mantua lakes in
      the hyporhithron fluvial zone and two stations were located in the potamon
      fluvial zone between the Mantua lakes and the confluence with the Po River. A
      total of 133 species of active trophic ciliates belonging to 76 genera were
      found. Community structures revealed in this data were analysed using some
      statistical methods (similarity index, and categorical principal component
      analysis (CATPCA)) and this allowed the determination of differences between
      stations and between ciliate communities characteristic of stations. Species
      typical of the ecotypes located in both rhithron and potamon fluvial zones were
      defined. The saprobic index and valency analysis methods were used to quantify
      organic input and to follow changes in saprobicity along the river. A change in
      the ciliate communities was observed between stations located upstream and
      stations located downstream of the town of Mantua. The former were composed
      mainly of beta-mesosaprobic species, typical of the hill zone of running waters,
      while in the latter increased numbers of alpha-mesosaprobic species are
      associated with the higher anthropogenic pressures. Our results reiterate the
      high sensitivity shown by ciliated protozoa as indicators of organic load in
      watercourses.

PMID- 17222542
TI  - Immunomodulating polysaccharides from the lichen Thamnolia vermicularis var.
      subuliformis.
AB  - Three heteroglycans Ths-4, Ths-5 and thamnolan and a beta-glucan, Ths-2, isolated
      from the lichen Thamnolia vermicularis var. subuliformis were tested for in vitro
      immunomodulating activities and shown to have various influences on the immune
      system. All the polysaccharides except Ths-4 caused a stimulation of rat spleen
      cell proliferation. In contrast, Ths-4 caused cell death early in the culture,
      probably due to over-stimulation. Moreover, the galactofuranomannans, Ths-4, Ths
      5 and the beta-glucan Ths-2, induced rat spleen cells to secrete IL-10
      significantly above background levels. In addition, Ths-4 and Ths-5 stimulated
      significant TNF-alpha secretion by rat peritoneal macrophages. The
      galactofuranomannans Ths-4 and Ths-5 have similar structures apart from the
      molecular weight. Thus, it may be concluded that the molecular size might
      influence the potency but not the pattern of activity for Ths-4 and Ths-5. The
      galactofuranorhamnan thamnolan had less mitogenic effect than Ths-5 and Ths-2 and
      neither induced IL-10 secretion by rat spleen cells nor TNF-alpha secretion by
      peritoneal macrophages to significant levels. This shows that thamnolan with its
      unusual galactofuranorhamnan structure differs from the other Thamnolia
      polysaccharides in its immunomodulatory activity.

PMID- 17222543
TI  - Misexpression of Sox9 in mouse limb bud mesenchyme induces polydactyly and
      rescues hypodactyly mice.
AB  - Our previous studies have demonstrated the essential roles of the transcription
      factor Sox9 in the commitment of mesenchymal cells to a chondrogenic cell lineage
      and in overt chondrogenesis during limb bud development. However, it remains
      unknown if Sox9 induces chondrogenesis in mesenchyme ectopically in vivo as a
      master regulator of chondrogenesis. In this study, we first generated mutant mice
      in which Sox9 was misexpressed in the limb bud mesenchyme. The mutant mouse
      embryos exhibited polydactyly in limb buds in association with ectopic expression
      of Sox5 and Sox6 although markers for the different axes of limb bud development
      showed a normal pattern of expression. Misexpression of Sox9 stimulated cell
      proliferation in limb bud mesenchyme, suggesting that Sox9 has a role in
      recruiting mesenchymal cells to mesenchymal condensation. Second, despite the
      facts that misexpression of Sonic hedgehog (Shh) induces polydactyly in a number
      of mutant mice and Shh-null mutants have severely defective cartilage elements in
      limb buds, misexpression of Sox9 did not restore limb bud phenotypes in Shh-null
      mutants. Rather, there was no expression of Sox9 in digit I of Hoxa13Hd mutant
      embryos, and Sox9 partially rescued hypodactyly in Hoxa13Hd mutant embryos. These
      results provide evidence that Sox9 induces ectopic chondrogenesis in mesenchymal
      cells and strongly suggest that its expression may be regulated by Hox genes
      during limb bud development.

PMID- 17222544
TI  - Diagnosis and management of pulmonary hypertension over the past 100 years.
AB  - Pulmonary hypertension is a rare disease with a poor prognosis. It was first
      described in the late 19th century as a clinical-pathological syndrome
      characterised by obstruction of the small pulmonary arteries and right
      ventricular hypertrophy in patients presenting with severe dyspnoea and cyanosis.
      After the development of right heart catheterisation in the second half of the
      20th century, it was found that many diseases could cause pulmonary hypertension,
      which is now recognised to be high blood pressure in the arteries that supply the
      lungs. In the 1960s, an epidemic of pulmonary hypertension caused by appetite
      suppressants initiated a systematic collection of information on pulmonary
      hypertension, leading to the first international classification of pulmonary
      hypertension. Increased understanding of the pathogenesis of the various forms of
      pulmonary hypertension has led to novel treatments and holds promise for the
      future.

PMID- 17222545
TI  - Ten-year survival and risk of relapse for testicular cancer: a EUROCARE high
      resolution study.
AB  - Effective treatments for testicular cancer have been available since the 1970s,
      yet EUROCARE uncovered marked inter-country survival differences for this
      disease. To investigate these differences, we reviewed clinical records of 1350
      testicular cancer cases diagnosed during 1987-1992 from 13 population-based
      cancer registries in nine European countries. Patients were followed up for life
      status and relapse. Ten-year observed survival was estimated by the Kaplan-Meier
      method. Cox multivariable analyses were performed separately for seminomas and
      non-seminomas. Overall, 66% of seminomas and 36% of non-seminomas were limited to
      the testis. Ten-year survival was 63% (Estonia) to 94% (Switzerland, Slovenia)
      for seminoma; 47% (Estonia) to 90% (Yorkshire, UK, The Netherlands) for non
      seminoma. Multivariable analysis adjusted for country, age and stage showed that
      hazard ratios (HRs) of death differed little between western European registries,
      and were mainly attributable to differing stage at diagnosis. Significantly
      higher than reference HRs in Estonia and Poland suggest inadequacy or
      unavailability of treatments.

PMID- 17222546
TI  - Tumour volume and high grade tumour volume are the best predictors of pathologic
      stage and biochemical recurrence after radical prostatectomy.
AB  - INTRODUCTION: Our goal was to examine to what extent tumour volume (TV) and
      percentage of high grade tumour volume (%HGTV) affect the rate of positive
      surgical margins and the rate of biochemical recurrence after radical
      prostatectomy. MATERIALS AND METHODS: TV and %HGTV were routinely planimetrically
      quantified in a cohort of 780 consecutive patients. Mean follow-up was 46.7
      months. Multivariable regression models addressed two separate endpoints:
      positive surgical margins and biochemical recurrence. The increase in model
      predictive accuracy related to the addition of TV and %HGTV to radical
      prostatectomy stage and grade was assessed, after 200 bootstrap resamples to
      reduce overfit bias. RESULTS: In multivariable logistic regression models
      addressing positive surgical margins rate, predictive accuracy increased by 1.9%
      (p<0.001) when TV was added to other covariates. No further increment was noted
      when %HGTV was added (p=0.3). In multivariable Cox regression models addressing
      biochemical recurrence, accuracy increased by 0.6% (p=0.002) when TV was added
      and an additional increase of 0.7% was recorded when %HGTV (p<0.001) was added.
      CONCLUSION: Tumour bulk reflected by TV affects local cancer control rate, which
      is reflected in the rate of positive surgical margins. Conversely, high grade
      cancer determines the rate of biochemical recurrence. These two variables
      represent the most powerful predictors of cancer control in men treated for
      localised prostate cancer. Moreover, they increase the ability of established
      predictors to predict the outcomes of interest. In consequence, they warrant
      consideration in future predictive and prognostic tools.

PMID- 17222547
TI  - Allelic variants of CAMTA1 and FLJ10737 within a commonly deleted region at 1p36
      in neuroblastoma.
AB  - Deletion of a distal portion of 1p is seen in a wide range of human malignancies,
      including neuroblastoma. Here, a 1p36.3 commonly deleted region of 216 kb has
      been defined encompassing two genes, CAMTA1 and FLJ10737. Low expression of
      CAMTA1 has been recently shown to be an independent predictor of poor outcome in
      neuroblastoma patients. The present study surveys CAMTA1 and FLJ10737 for genetic
      alterations by fluorescence-based single strand conformation polymorphism (SSCP)
      using a panel of DNAs from 88 neuroblastomas, their matching blood samples and 97
      unaffected individuals. Nucleotide variants encoding amino acid substitutions
      were found in both genes. One CAMTA1 variant (T1336I) was not detected in 97
      unaffected individuals, another (N1177K) resides in a conserved domain of the
      CAMTA1 protein and was found hemizygous in six neuroblastomas. We found no
      evidence for somatic mutations in FLJ10737 or CAMTA1. Further investigations are
      needed to address the functional impact of the identified variants and their
      possible significance for neuroblastoma.

PMID- 17222548
TI  - Physical activity and stomach cancer risk: the influence of intensity and timing
      during the lifetime.
AB  - Physical inactivity is linked to risk for cancers of the colon, breast, lung and
      endometrium, but few data exist on this association with stomach cancer. We
      evaluated the association between recreational physical activity and incident
      stomach cancer in a case-control study. The data yielded odds ratios suggestive
      of approximately 20-40% reduced risk of stomach cancer when comparing more
      frequent (3+ times/week) to less frequent (<1/month) strenuous activities. The
      magnitudes of the associations for strenuous physical activities were consistent
      across the teens, early 30s, and early 50s. Compared to the least active
      quartile, the second, third, and fourth quartiles of average lifetime strenuous
      physical activity yielded odds ratios of 0.82, 0.69, and 0.58 (95% CI, 0.41
      0.83), respectively. Odds ratios for moderate activity generally suggested a
      modest, but not statistically significant, inverse association. Increased
      strenuous physical activity, throughout the lifespan, was associated with
      decreased risk of incident stomach cancer.

PMID- 17222549
TI  - The case for improving vitamin D status.
AB  - Evidence from both physiological experiments and randomized trials demonstrates
      that elevating vitamin D status above levels prevailing in the North American and
      European adult populations improves calcium absorption and reduces fall risk and
      osteoporotic fractures. Additionally observational data suggest that raising
      vitamin D status protects against various cancers and autoimmune disorders as
      well. Hence a strong case can be made for immediate improvement in vitamin D
      status of the general population.

PMID- 17222550
TI  - Sun protection and Vitamin D: three dimensions of obfuscation.
AB  - Ultraviolet (UV) radiation is a proven carcinogen, responsible for more than half
      of all human malignancies. It also compromises skin appearance and function.
      Since the UV action spectra for DNA damage, skin cancer and Vitamin D(3) (vit D)
      photosynthesis are identical and vit D is readily available from oral
      supplements, why has sun protection become controversial, now that some data
      suggest conventionally "sufficient" levels of vit D may be less than optimal for
      at least some population groups? First, the media and apparently some researchers
      are hungry for a new message. Nevertheless, after 50 years, UV exposure is still
      a major avoidable health hazard. Second, the controversy is fueled by a powerful
      special interest group: the indoor tanning industry. They target not the frail
      elderly or inner-city ethnic minorities, groups for whom evidence of vit D
      insufficiency is strongest, but rather fair-skinned teenagers and young adults,
      those at highest risk of UV photodamage. Third, evolution does not keep pace with
      civilization. When nature gave man the appealing capacity for vit D
      photosynthesis, the expected lifespan was far less than 40 years. Long-term
      photodamage was not a concern, and vit D was not available at the corner store.
      The medical community should avoid sensationalism and instead rigorously explore
      possible cause-and-effect relationships between vit D status and specific
      diseases while advocating the safest possible means of assuring vit D
      sufficiency.

PMID- 17222551
TI  - Alkaline degradation of invert sugar from molasses.
AB  - Sugar beet and sugar cane molasses have been shown to be suitable starting
      materials for producing de-icer preparations. The sucrose in the molasses is
      hydrolyzed to glucose and fructose by invertase. The reducing sugars are then
      degraded by NaOH, the alkali being neutralized by the sugar acids produced,
      resulting in an increase of the ionic strength and consequently depression of the
      freezing point of the resulting solution. For the preparation of de-icers, the
      desired freezing point depression to a temperature of less than about -20 degrees
      C can be achieved by adjusting the amount and concentration of the alkali metal
      hydroxide used. The resulting products are biodegradable and eliminate the
      corrosive effects associated with the use of conventional chloride salts.
      Degradation of invert sugar by NaOH has been achieved without an external heat
      source. The reaction products showed the same freezing point depression as seen
      in the degradation products from pure glucose.

PMID- 17222552
TI  - Laboratory composting of extruded starch acetate and poly lactic acid blended
      foams.
AB  - Composting of extruded foams made of starch acetate and poly lactic acid (PLA)
      with pre-conditioned yard waste was studied using a laboratory composting system.
      Extruded foams of high amylose starch were used as the control. Degradation was
      measured by analyzing the exhaust gases for carbon dioxide. There were
      significant differences in the amounts of carbon dioxide produced in the vessels
      containing foams of high amylose starch and foams of starch acetate blended with
      20% or 30% PLA. The high amylose starch foams completely degraded within 15 days.
      The starch acetate foams with 0% PLA took longer, with evolution of carbon
      dioxide still measurable after 55 days. The rate of degradation was faster for
      foams with higher PLA contents. The starch acetate foams took even longer to
      degrade. The maximum time was found to be 130 days for the starch acetate foams.

PMID- 17222553
TI  - Enzyme enhanced solid-state fermentation of kenaf core fiber for storage and
      pretreatment.
AB  - Kenaf is an annual fiber crop adaptable to a wide range of climates and soil
      types. This study investigated the use of kenaf core fiber as a feedstock for
      enzyme-enhanced fermentation. Triplicate kenaf core fiber samples were treated
      with enzymes having cellulase:hemicellulase activity ratios of 0:1, 0.015:1,
      0.45:1, and 2.54:1 at a rate of 5010 IU/kg dry matter hemicellulase activity,
      vacuum-sealed, and incubated at 37 degrees C for 21 d. Samples were analyzed for
      pH, water soluble carbohydrates, organic acids, and hemicellulose and cellulose
      concentrations. All treatments produced a pH less than 4.0, which is sufficient
      for stable storage. Treatments with 2.54:1 and 0.45:1 produced the highest water
      soluble carbohydrate and lactic acid concentrations. Enzymes with no or low
      cellulase activity produced results similar to the control. Utilizing enzyme
      mixtures with high cellulase activity is an effective pretreatment method for
      ensiled kenaf core fiber.

PMID- 17222554
TI  - The utilization of beet molasses as a novel carbon source for cephalosporin C
      production by Acremonium chrysogenum: Optimization of process parameters through
      statistical experimental designs.
AB  - In this work, cephalosporin C (CPC) production on pilot scale fermenters of 600l
      capacity with 350l working volume by Acremonium chrysogenum EMCC 904 was
      performed. The effects of fermentation medium composition, inoculum
      concentration, initial pH and aeration rate on CPC production by A. chrysogenum
      strain was investigated by using response surface methodology (RSM). The Plackett
      Burman design which involves two concentrations of each nutrient was effective in
      searching for the major medium components promoting CPC production. Under our
      experimental conditions; Soya oil, beet molasses and corn steep liquor were found
      to be the major factors contributing to the antibiotic production. Subsequently,
      a Box-Behnken design was used for outlining the concentration of the most
      effective medium constituents. Estimated optimum composition for the production
      of CPC was as follows: soya oil, 40g/l; beet molasses, 180g/l; and corn steep
      liquor, 330g/l. The central composite design was used for outlining the optimum
      values of the fermentation parameters. Estimated optimum values for the
      production of CPC are as follows: inoculum level, 10(5.5)spores/ml; initial pH,
      4.3; and aeration rate, 9364ml/min.

PMID- 17222555
TI  - Incorporation of Drosophila CID/CENP-A and CENP-C into centromeres during early
      embryonic anaphase.
AB  - The centromere/kinetochore complex is indispensable for accurate segregation of
      chromosomes during cell divisions when it serves as the attachment site for
      spindle microtubules. Centromere identity in metazoans is believed to be governed
      by epigenetic mechanisms, because the highly repetitive centromeric DNA is
      neither sufficient nor required for specifying the assembly site of the
      kinetochore. A candidate for an epigenetic mark is the centromere-specific
      histone H3 variant CENP-A that replaces H3 in alternating blocks of chromatin
      exclusively in active centromeres. CENP-A acts as an initiator of kinetochore
      assembly, but the detailed dynamics of the deposition of metazoan CENP-A and of
      other constitutive kinetochore components are largely unknown. Here we show by
      quantitative fluorescence measurements in living early embryos that functional
      fluorescent fusion proteins of the Drosophila CENP-A and CENP-C homologs are
      rapidly incorporated into centromeres during anaphase. This incorporation is
      independent of ongoing DNA synthesis and pulling forces generated by the mitotic
      spindle, but strictly coupled to mitotic progression. Thus, our findings uncover
      a strikingly dynamic behavior of centromere components in anaphase.

PMID- 17222556
TI  - Osteochondritis dissecans of the knee; long-term clinical outcome following
      arthroscopic debridement.
AB  - We reviewed 32 knees in 26 patients who had previously undergone arthroscopic
      debridement for symptomatic osteochondritis dissecans (OCD) of the knee. The
      patients were followed up at a minimum of 11 years following surgery and were
      evaluated clinically using the American Knee Society Clinical Rating Score.
      Additional evaluation was performed using the Hughston Scale to include
      radiographic assessment. The mean American Knee Society Score was 179 (out of
      200), indicating good clinical function. Radiographically, however, only 29%
      scored excellent or good on the Hughston Scale. Younger patients with a small,
      stable (and therefore preserved), medial femoral condyle lesion had the best
      prognosis. Whilst more novel and complex options such as chondrocyte implantation
      are being assessed for the treatment of OCD, it is clear that within this study
      group careful debridement with removal of loose tissue can achieve good clinical
      results in the long term. There was however radiographic evidence of early
      degenerative joint disease in 17/24 (71%) of patients reviewed. Patients
      undergoing excision of OCD fragments did worse than those in whom the fragment
      was preserved, however the risk of further surgery is raised if a fragment is
      left in situ at initial surgery.

PMID- 17222557
TI  - Isolated patellofemoral osteoarthritis.
AB  - Isolated patellofemoral osteoarthritis is now recognised to be more common than
      previously thought. The features and management are reviewed, including the
      various surgical options in symptomatic patients. The evidence base for managing
      patellofemoral osteoarthritis is behind that for the tibiofemoral joint. All
      treatments are based on uncontrolled observational case series, typically
      retrospectively reviewed. Fortunately the majority of patients with isolated
      patellofemoral degenerative changes do not need surgical treatment. Those who are
      symptomatic can usually be successfully treated with weight loss and quadriceps
      strengthening exercises.

PMID- 17222558
TI  - 1,4-Bis(alkylamino)benzo[g]phthalazines able to form dinuclear complexes of
      Cu(II) which as free ligands behave as SOD inhibitors and show efficient in vitro
      activity against Trypanosoma cruzi.
AB  - The synthesis of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1-3 is
      reported, and their ability to form dinuclear complexes with Cu(II) assayed. The
      geometry of the complexes is dependent on the nature of the electron-donor sites
      at the sidechains. Compounds 1 and 2, that contain sp3 or sp2 nitrogens at the
      end of the alkylamino groups, originate monopodal dinuclear complexes which seem
      to include endogenous OH bridges, and the sidechains seem to actively participate
      in complexation. However, the substitution of nitrogen by oxygen in 3 leads to a
      tripodal dinuclear complex in which the sidechains are not involved. The in vitro
      antiparasitic activity on Trypanosoma cruzi epimastigotes and amastigotes and the
      SOD activity inhibition have been evaluated for compounds 1-3, and, as expected,
      1 and 2 show in all cases relevant results, whereas 3 is always the less active
      among the three substrates tested.

PMID- 17222560
TI  - Surgical management of pulmonary atresia with ventricular septal defect in late
      adolescence and adulthood.
AB  - OBJECTIVE: In presence of adequate pulmonary blood flow, patients presenting with
      unoperated or palliated pulmonary atresia with ventricular septal defect (PA/VSD)
      can reach adult age. However, they remain symptomatic with a limited life
      expectancy. METHODS: Since 1993, 27 patients underwent surgery for unrepaired
      PA/VSD. Median age was 20 (range: 15-43) years. Nineteen patients had 33 previous
      palliative procedures while eight were unoperated survivors. Major aortopulmonary
      collateral artery (MAPCA) had been observed in all but 2 and were still patent in
      23. All bronchopulmonary segments were connected to the native pulmonary arteries
      (NPA) in 4 (type A), to both NPA and MAPCA in 18 (type B) and only to MAPCA in 5
      (type C). The biventricular repair was performed in 17 patients: 3 type A, 12
      type B and 2 type C. Ten patients underwent palliative procedure: eight
      aortopulmonary shunt, with unifocalisation in two and one right ventricle to NPA
      restrictive conduit. RESULTS: One (4%) hospital death occurred following the
      failure of a palliative procedure. No clinical improvement was observed in seven
      patients including one repaired and six palliated survivors. Two late cardiac
      death occurred 1 and 7 years after repair. At last visit, 15 of 16 repaired
      survivors were in NYHA class I or II. Only one patient awaits septation, while
      eight other with subsequent palliation were considered not repairable.
      CONCLUSION: The outcome was encouraging in patients who were eligible for
      completed biventricular repair. Although considered as unique alternative to
      cardiopulmonary transplantation, the justification for palliative surgery to
      improve pulmonary blood flow remains to be established.

PMID- 17222559
TI  - Acute and long-term effects of botulinum neurotoxin on the function and structure
      of developing extraocular muscles.
AB  - Strabismus is a misalignment of the visual axes, due to an imbalance in
      extraocular muscle (EOM) function. Botulinum neurotoxin (BoNT) treatment can
      correct the misalignment with permanent therapeutic effects in infants, possibly
      because the toxin causes structural alterations in developing EOM. To determine
      whether BoNT indeed permanently weakens developing EOMs, we examined the chicken
      oculomotor system. Following injections of BoNT in hatchling chicks, we
      quantified physiological parameters (contractile force measurements) and
      morphological parameters (myofiber morphometry, innervation, quantitative
      transmission electron microscopy of mitochondria/fiber types). Treatment of
      developing EOM with BoNT caused acute reductions of muscle strength and
      mitochondrial densities, but minimal changes in muscle fiber diameter and
      neuromuscular junction structures. Contrary to expectations, contractile force
      was fully recovered by 3-4 months after treatment. Thus, permanent therapeutic
      effects of BoNT most likely do not cause permanent changes at the level of the
      peripheral effector organ, but rather involve central (CNS) adaptive responses.

PMID- 17222561
TI  - An audit of surgical outcomes of esophageal squamous cell carcinoma.
AB  - OBJECTIVE: Esophageal squamous cell carcinoma and adenocarcinoma were
      increasingly recognized as two entities with different biologic behaviors and
      prognosis. Surgical risks and oncologic benefits of transthoracic and transhiatal
      esophagectomy for esophageal squamous cell carcinoma patients are not confessed.
      METHODS: Between 1994 and 2005, 216 esophageal squamous cell carcinoma patients
      underwent esophagectomy were enrolled and analyzed retrospectively. RESULTS: One
      hundred sixty-six patients underwent transthoracic esophagectomy and 50 patients
      underwent transhiatal esophagectomy. The overall hospital mortality and
      postoperative complication rates were 9.7 and 49%, respectively. The amount of
      intra-operative blood loss or transfusion, postoperative complication rate,
      lengths of hospital stay and hospital mortality rate were not significantly
      different between both groups. However, shorter operative time was noticed in
      transhiatal group (p<0.001). The overall 5-year survival rate was 16.8%. ESCC
      patients underwent either transthoracic or transhiatal esophagectomy had
      comparable long-term survival. The pTNM stage was independent prognostic factor
      for patients underwent transthoracic esophagectomy. However, location of tumor
      (p=0.009) and pathologic tumor length (p=0.012) were predictors of prognosis for
      patients underwent transhiatal esophagectomy. CONCLUSIONS: For esophageal
      squamous cell carcinoma patients, no significant differences in postoperative
      mortality or morbidity rates were observed between transthoracic and transhiatal
      esophagectomy. However, traditional pTNM staging system might underestimate the
      severity of esophageal squamous cell carcinoma patients who underwent transhiatal
      esophagectomy. The information of dissimilar prognostic factors for transhiatal
      or transthoracic esophagectomies will be helpful in tailoring more individualized
      adjuvant therapy to optimize esophageal squamous cell carcinoma patient's
      outcome.

PMID- 17222562
TI  - Tyrosine hydroxylase expression is unstable in a human immortalized mesencephalic
      cell line--studies in vitro and after intracerebral grafting in vivo.
AB  - We have studied the stability of the dopaminergic phenotype in a conditionally
      immortalized human mesencephalic cell line, MESC2.10. Even though MESC2.10 cells
      exhibit features of dopaminergic neurons in vitro, none of the cells expressed
      tyrosine hydroxylase (TH) after transplantation into a rat model of Parkinson's
      disease. We examined whether this is caused by cell death or loss of transmitter
      phenotype. Cells were cultured in differentiation medium, then harvested and
      replated into the same medium where they continued to express TH, whereas
      replated cells fed medium lacking differentiation factors (dibutyryl cAMP and
      glial cell line-derived neurotrophic factor) did not. Interestingly, cultures
      grown in the absence of differentiation factors could regain TH expression once
      exposed to differentiation medium. Our data suggest that TH expression in vitro
      is inducible in neurons derived from the MESC2.10 cell line and that the
      dopaminergic phenotype of these cells in vivo might be unstable.

PMID- 17222563
TI  - Continuous representations of proteins: construction of coordinate models from
      curvature profiles.
AB  - A representation of proteins based on the geometry of space curves is described.
      This representation enables the application of continuum methods to the analysis
      of macromolecular structure and form that cannot be applied to the more familiar
      discrete atomic coordinate models. It is shown that the continuous modeling
      method defines the geometry of the protein fold very efficiently. An analytical
      solution for curve construction is employed from which both continuous and
      coordinate models can be obtained. The method is applied to five representative
      test proteins which are used to assess the accuracy and efficiency of the
      modeling procedure.

PMID- 17222564
TI  - Is attention necessary for object identification? Evidence from eye movements
      during the inspection of real-world scenes.
AB  - Eye movements were recorded during the display of two images of a real-world
      scene that were inspected to determine whether they were the same or not (a
      comparative visual search task). In the displays where the pictures were
      different, one object had been changed, and this object was sometimes taken from
      another scene and was incongruent with the gist. The experiment established that
      incongruous objects attract eye fixations earlier than the congruous
      counterparts, but that this effect is not apparent until the picture has been
      displayed for several seconds. By controlling the visual saliency of the objects
      the experiment eliminates the possibility that the incongruency effect is
      dependent upon the conspicuity of the changed objects. A model of scene
      perception is suggested whereby attention is unnecessary for the partial
      recognition of an object that delivers sufficient information about its visual
      characteristics for the viewer to know that the object is improbable in that
      particular scene, and in which full identification requires foveal inspection.

PMID- 17222565
TI  - The role of the posterior superior temporal sulcus in the processing of unmarked
      transitivity.
AB  - Is it living or not? The ability to differentiate between animate and inanimate
      entities is of considerable value in everyday life, since it allows for the
      dissociation of individuals that may willfully cause an action from objects that
      cannot. The present fMRI study aimed to shed light on the neural correlates of
      animacy at a relational-interpretive level, i.e. on the role of animacy in the
      establishment of relations between entities that are more or less likely to cause
      an event and differ in their potential to act volitionally. To this end, we
      investigated the processing of visually presented transitive German sentences
      (nominative-accusative structures) in which the factors animacy and argument
      order were manipulated. The relations between the arguments differed in that the
      animate subject either acted on an inanimate object (a very natural construction
      in terms of transitivity) or on an animate object (resulting in a sentence
      deviating from an unmarked transitive structure). Participants performed an
      acceptability judgment task. Violations of unmarked transitivity yielded a
      significant activation increase within the posterior left superior temporal
      sulcus (pSTS), thus suggesting a specific role of this cortical region in the
      relational use of animacy information. This result indicates that the influence
      of animacy as a relational feature differs from the impact of this parameter on
      the word level and is in line with other neuroimaging studies showing an
      engagement of the pSTS when a matching between syntax and semantics is required.
      A comparison between object- and subject-initial conditions further revealed a
      robust effect of argument order in the pars opercularis of the left inferior
      frontal gyrus (a subregion of Broca's area), thereby replicating previous
      findings demonstrating a sensitivity of this region to fine-grained language
      specific linearization rules.

PMID- 17222566
TI  - Non-normality and transformations of random fields, with an application to voxel
      based morphometry.
AB  - Parametric tests of linear models for images modeled as random fields are based
      like ordinary univariate tests on distributional assumptions. It is here shown
      that the effect of departures from assumptions in random field tests is more
      pronounced than in the univariate condition. Simulations are presented
      investigating in detail the influence of smoothing, unbalancedness and leverages
      on empirical thresholds. In certain conditions, significance tests may become
      invalid. As a case study, the existence and effect of departures from normality
      of gray matter probability maps, commonly used in voxel-based morphometry, is
      investigated, as well as the effect of different transformation strategies
      involving estimating the degree of transformation from the data by maximum
      likelihood. The best results are achieved with a voxel-by-voxel transformation,
      suggesting heterogeneity of distributional form across the volume for this kind
      of data.

PMID- 17222568
TI  - Utility of imaging mass spectrometry (IMS) by matrix-assisted laser desorption
      ionization (MALDI) on an ion trap mass spectrometer in the analysis of drugs and
      metabolites in biological tissues.
AB  - INTRODUCTION: The properties and potential liabilities of drug candidate are
      investigated in detailed ADME assays and in toxicity studies, where findings are
      placed in context of exposure to dosed drug and metabolites. The complex nature
      of biological samples may necessitate work-up procedures prior to high
      performance liquid chromatography-mass spectrometric (HPLC-MS) analysis of
      endogenous or xenobiotic compounds. This concept can readily be applied to
      biological fluids such as blood or urine, but in localized samples such as organs
      and tissues potentially important spatial, thus anatomical, information is lost
      during sample preparation as the result of homogenization and extraction
      procedures. However, the localization of test article or spatial identification
      of metabolites may be critical to the understanding of the mechanism of target
      organ toxicity and its relevance to clinical safety. METHODS: Tissue imaging mass
      spectrometry (IMS) by matrix-assisted laser desorption ionization (MALDI) and ion
      trap mass spectrometry (MS) with higher order mass spectrometric scanning
      functions was utilized for localization of dosed drug or metabolite in tissue.
      Laser capture microscopy (LCM) was used to obtain related samples from tissue for
      analyses by standard MALDI-MS and HPLC-MS. RESULTS: In a toxicology study, rats
      were administered with a high dosage of a prodrug for 2 weeks. Birefringent
      microcrystalline material (10-25 microm) was observed in histopathologic formalin
      fixed tissue samples. Direct analysis by IMS provided the identity of material in
      the microcrystals as circulating active drug while maintaining spatial
      orientation. Complementary data from visual cross-polarized light microscopy as
      well as standard MALDI-MS and HPLC-MS experiments on LCM samples validated the
      qualitative results obtained by IMS. Furthermore, the HPLC-MS analysis on the LCM
      samples afforded a semi-quantitative assessment of the crystalline material in
      the tissue samples. DISCUSSION: IMS by MALDI ion trap MS proved sensitive,
      specific, and highly amenable to the image analysis of traditional small molecule
      drug candidates directly in tissue.

PMID- 17222567
TI  - Depth-resolved optical imaging and microscopy of vascular compartment dynamics
      during somatosensory stimulation.
AB  - The cortical hemodynamic response to somatosensory stimulus is investigated at
      the level of individual vascular compartments using both depth-resolved optical
      imaging and in-vivo two-photon microscopy. We utilize a new imaging and
      spatiotemporal analysis approach that exploits the different characteristic
      dynamics of responding arteries, arterioles, capillaries and veins to isolate
      their three-dimensional spatial extent within the cortex. This spatial
      delineation is validated using vascular casts. Temporal delineation is supported
      by in-vivo two-photon microscopy of the temporal dynamics and vascular mechanisms
      of the arteriolar and venous responses. Using these techniques we have been able
      to characterize the roles of the different vascular compartments in generating
      and controlling the hemodynamic response to somatosensory stimulus. We find that
      changes in arteriolar total hemoglobin concentration agree well with arteriolar
      dilation dynamics, which in turn correspond closely with changes in venous blood
      flow. For 4-s stimuli, we see only small changes in venous hemoglobin
      concentration, and do not detect measurable dilation or ballooning in the veins.
      Instead, we see significant evidence of capillary hyperemia. We compare our
      findings to historical observations of the composite hemodynamic response from
      other modalities including functional magnetic resonance imaging. Implications of
      our results are discussed with respect to mathematical models of cortical
      hemodynamics, and to current theories on the mechanisms underlying neurovascular
      coupling. We also conclude that our spatiotemporal analysis approach is capable
      of isolating and localizing signals from the capillary bed local to neuronal
      activation, and holds promise for improving the specificity of other hemodynamic
      imaging modalities.

PMID- 17222569
TI  - Morphological differences between guinea pig aortic and venous endothelial cells
      in situ.
AB  - Endothelial cells (ECs) respond to fluid shear stress. They reveal shear stress
      related morphological changes in both their cell shape and cytoskeletal
      organization. Little is known about the cytoskeletal organization of ECs in situ.
      We studied, together with the living ultrasound high resolution imaging system,
      the distribution of stress fibers (SFs), certain focal adhesion (FA) and signal
      transduction associated proteins in guinea pig aortic and venous ECs. Although
      SFs present in the basal portion of venous ECs ran along the direction of the
      blood flow, their size was smaller and their number was fewer than those of
      aortic ECs. Venous ECs were elongated to the direction of flow than in aortic ECs
      exposed over normal shear stress (SS). Since fluid SS in the vein is low, a
      sustained and uni-directional low SS over a long period might thus cause these
      structural features observed in venous ECs.

PMID- 17222570
TI  - Expression and immunohistochemical localization of galectin-3 in various mouse
      tissues.
AB  - The expression and immunohistochemical localization of galectin-3, a beta
      galactoside-binding protein, was studied in several mouse tissues. Galectin-3
      expression was low in the cerebrum, heart, and pancreas, and moderate in the
      liver, ileum, kidney, and adrenal gland. High expression of galectin-3 was found
      in the lung, spleen, stomach, colon, uterus, and ovary. The results of Western
      blot analysis largely matched the immunohistochemical findings for galectin-3.
      These findings suggest that galectin-3 is differentially expressed in a variety
      of organs in the mouse. This study provides valuable information for research on
      galectin-3.

PMID- 17222571
TI  - Chromosome transfer activates and delineates a locus control region for perforin.
AB  - Perforin gene (PRF1) transcription regulates perforin expression in NK cells and
      CTL. Here we identified the locus-wide ensemble of cis-acting sequences that
      drives PRF1 transcription physiologically. By using chromosome transfer, we
      revealed that de novo activation of a silent PRF1 locus was controlled by a 150
      kb domain comprised of 16 DNase I hypersensitive sites (DHSs). These cis-acting
      sequences included a locus control region (LCR) and conferred developmentally
      appropriate and lineage-specific expression of human perforin from BAC
      transgenes. The LCR included four distal DHSs that were required for perforin
      expression from its natural locus, and their engineered deletion from the PRF1
      BAC transgene abolished LCR function and led to rapid gene silencing. Thus, LCR
      function is central for regulating the developmental and activation-specific PRF1
      promoter activity characteristic of NK cells and CTL.

PMID- 17222572
TI  - Identification of a T lineage-committed progenitor in adult blood.
AB  - With help of a hCD25 reporter controlled by pre-T cell receptor alpha (Ptcra)
      regulatory elements, T cell precursors were identified in peripheral blood. Sca
      1(+)IL-7Ralpha(+)Flt3(-) precursors that were c-kit(lo)Thy-1(hi) generated T
      lineage cells when cultured on OP9-DL1 stromal cells and upon transfer into Rag2(
      /-)Il2rg(-/-) mice. No B cells were generated in vivo and only few in vitro.
      These cells, which we call circulating T cell progenitors (CTP), were found at
      the same frequency in Foxn1(nu/nu) thymus-deficient mice and wild-type mice,
      indicating that they were pre- rather than postthymic. Inhibition of Notch
      dependent transcription in vivo reduced the frequency of intrathymic early T cell
      progenitors (ETP), but not CTP, indicating that the latter are less Notch
      dependent. Thus, CTP represent T lineage-committed T cell precursors linking
      extrathymic with intrathymic lymphopoiesis in adult mice.

PMID- 17222573
TI  - Fatal massive hemolysis as the first manifestation of Clostridium perfringens
      septicemia in a patient with non-systematic or local predisposing disorder.
AB  - We report a case of fulminant massive hemolysis due to Clostridium perfringens
      septicemia in an elderly patient with non-systematic or local predisposing
      disorder. The patient presented with atypical symptoms but the progress of the
      disease was extremely rapid and he died almost 3h after his hospital admission. A
      focal infection or a possible portal of bacterial access was not found.

PMID- 17222574
TI  - Osteitis deformans (Paget's disease) in a Burmese python (Python molurus
      bivittatus)--a case report.
AB  - Osteitis deformans (Paget's disease of bone) is a chronic focal disorder of bone
      remodelling characterized by an initial increase in osteoclast-mediated bone
      resorption, with subsequent compensatory increase in new bone formation,
      resulting in a disorganized mosaic of woven and lamellar bone. In the Burmese
      python (Python molurus bivittatus) of this report, multifocal gross swellings
      involving the proximal third of the vertebral spine were observed and associated
      with anorexia, a relative inability to move or to fully extend the body, and to
      strike at prey. Serum biochemistry revealed elevated alkaline-phosphatase
      activity. Radiographic changes (irregular bone proliferation along the vertebral
      margins), computed tomography scan results (abnormal mineral density), and
      histopathological features (generalized thickening of the bony trabeculae at the
      expense of the intertrabecular spaces and irregular patches of lamellar bone with
      a characteristic "mosaic" pattern) indicated osteitis deformans.

PMID- 17222575
TI  - T3 replacement does not prevent excitotoxic cell death but reduces developmental
      neuronal apoptosis in newborn mice.
AB  - BACKGROUND: Periventricular leukomalacia (PVL) is a major cause of neurological
      handicap in pre-term infants. At present, there are no effective or causal
      therapies available. Thyroid hormones play an essential role in brain development
      and are reported to be decreased in pre-terms and following brain injury in
      adults. HYPOTHESIS: Excitotoxic brain damage of newborn mice decreases thyroid
      hormone concentrations. Exogenous T3 administration restores thyroid hormone
      levels and reduces perinatal brain damage in an animal model of PVL. DESIGN AND
      METHOD: To create white and gray matter (WM/GM) lesion mimicking several key
      aspects of PVL, we injected ibotenic acid (Ibo), a glutamate analog, into the
      right hemisphere (intracranially (i.c.)) of 5-day-old mice. T3 (10 microg/kg body
      weight (bw)) was injected intraperitoneally (i.p.) 1 h or repeatedly
      1/24/48/72/96 h post-insult. We determined lesion size, number of apoptotic cells
      in WM/GM and serum T3/T4 concentration at 24 and 120 h after injury. Serum T3/T4
      concentration was also determined before and 1 and 2h after T3 administration.
      RESULTS: Excitotoxic brain damage did not alter serum T3/T4 concentrations within
      120 h of injury. Serum T3 levels were distinctly elevated within 1 h of T3
      injection; however, this elevation was relatively short-lived (half-life
      estimated to be less than 12 h). Neither single nor repetitive T3 treatment
      regimen reduced excitotoxic lesion size, but it did reduce apoptosis.
      CONCLUSIONS: T3 replacement does not prevent excitotoxic cell death, but it does
      reduce developmental neuronal apoptosis, which could participate to the
      beneficial neuropsychological effects of hormone therapy. Further study is
      therefore warranted.

PMID- 17222576
TI  - Eosinophilic fibrosing gastritis and toxoplasmosis in a cat.
AB  - A 3-year-old, neutered male Tiffany cat was presented to the Animal Health Trust
      for investigation of pyrexia and a gastric lesion. Radiography and ultrasound
      showed severe thickening of the gastric wall and regional lymphadenopathy. There
      was altered gastric wall layering, predominately due to muscularis thickening.
      Histopathology confirmed eosinophilic fibrosing gastritis. The cat also had
      evidence of generalised Toxoplasma gondii infection, which may have been
      responsible for the gastric changes.

PMID- 17222577
TI  - [Clitoris and G spot: an intimate affair].
AB  - Ultrasonography is a good means for studying the clitoris and its relationship
      with the G spot. We used it to demonstrate that clitoral bodies have a descending
      movement and come close to the distal anterior vaginal wall during a voluntary or
      reflex contraction of levator ani muscles. This fact could explain the particular
      sensitivity of the G spot and its role in the orgasm.

PMID- 17222578
TI  - Human hydration level monitoring using embedded piezoresistive microcantilever
      sensors.
AB  - Embedded piezoresistive microcantilever (EPM) sensors were used to measure
      osmolality changes in both saliva mimic solutions and true human saliva.
      Osmolality changes in human saliva or urine may prove to be reliable, simple, and
      easy to measure markers for tracking human hydration levels. EPM sensors used in
      these experiments show good response to osmolality changes in both NaCl-based
      saliva mimic solutions and to human saliva. The addition of zero-point offset
      correction to EPM sensors allows for tracking of saliva osmolality changes with
      high accuracy. Also, the same EPM sensors exhibit a large enough range of
      osmolality response to make them potentially suitable for urine or blood serum
      osmolality monitoring.

PMID- 17222579
TI  - A threshold-based fall-detection algorithm using a bi-axial gyroscope sensor.
AB  - A threshold-based algorithm, to distinguish between Activities of Daily Living
      (ADL) and falls is described. A gyroscope based fall-detection sensor array is
      used. Using simulated-falls performed by young volunteers under supervised
      conditions onto crash mats and ADL performed by elderly subjects, the ability to
      discriminate between falls and ADL was achieved using a bi-axial gyroscope sensor
      mounted on the trunk, measuring pitch and roll angular velocities, and a
      threshold-based algorithm. Data analysis was performed using Matlab to determine
      the angular accelerations, angular velocities and changes in trunk angle
      recorded, during eight different fall and ADL types. Three thresholds were
      identified so that a fall could be distinguished from an ADL: if the resultant
      angular velocity is greater than 3.1 rads/s (Fall Threshold 1), the resultant
      angular acceleration is greater than 0.05 rads/s(2) (Fall Threshold 2), and the
      resultant change in trunk-angle is greater than 0.59 rad (Fall Threshold 3), a
      fall is detected. Results show that falls can be distinguished from ADL with 100%
      accuracy, for a total data set of 480 movements.

PMID- 17222580
TI  - Lrrk2 G2385R is an ancestral risk factor for Parkinson's disease in Asia.
AB  - The goal of genetic association studies is to identify common (>5%) risk factors
      in complex disease traits. Herein we describe the first replicable 'functional'
      risk allele for Parkinson's disease. The leucine-rich repeat kinase 2 (Lrrk2)
      G2385R substitution is associated with familial parkinsonism, late-, and early
      onset Parkinson's disease in ethnic Chinese Taiwanese. Crucially, we provide
      evidence of identity-by-descent and suggest that Lrrk2 G2385R carriers originate
      from one ancestor some 4800 years ago, at the start of Chinese civilization.
      Moreover, our findings demonstrate that common genetic coding variants contribute
      to Parkinson's disease in a population specific manner which may have important
      implications for future genome-wide association studies.

PMID- 17222581
TI  - Simultaneous Guillain-Barre syndrome and active human herpesvirus 6 infection in
      the central nervous system.

PMID- 17222582
TI  - Human respiratory coronavirus HKU1 versus other coronavirus infections in Italian
      hospitalised patients.
AB  - BACKGROUND: Human respiratory coronavirus (hCoV) HKU1 infections were reported
      for the first time in 2005 in Hong Kong. OBJECTIVE: To investigate
      epidemiological, clinical, and diagnostic features of HKU1 infections. STUDY
      DESIGN: Longitudinal, prospective study from November 2005 through May 2006 in a
      hospitalised patient population. RESULTS: Overall, 48/426 (11.3%) patients were
      found to be infected by hCoV acute respiratory tract infections (ARTI). Of these,
      10 (19.2%) were caused by HKU1 (6 single infections and 4 coinfections) during
      the period January-May 2006. Diagnosis was made by using RT-PCR for all four
      hCoVs, and in parallel, in-house developed group-specific monoclonal antibodies
      (MAbs) for HKU1 and 229E. HKU1-specific MAb was able to retrospectively identify
      8 of 10 HKU1 strains detected by RT-PCR. Phylogenetic analysis showed that four
      HKU1 strains were genotype A and six genotype B. In HKU1-infected patients, the
      predominant clinical symptom was rhinorrhea (nine patients). Within group II
      hCoV, HKU1-infected patients had a significantly lower rate of lower ARTI
      compared to OC43-infected patients. CONCLUSION: HKU1 hCoV strains circulated in
      northern Italy during the winter-spring season 2005-2006. Both HKU1 genotypes
      were detected. HKU1-specific MAb may contribute to the rapid diagnosis of HKU1
      infections currently performed by RT-PCR.

PMID- 17222583
TI  - Production of a novel recombinant Drosophila melanogaster acetylcholinesterase
      for detection of organophosphate and carbamate insecticide residues.
AB  - A novel recombinant Drosophila melanogaster acetylcholinesterase (R-DmAChE)
      produced in Pichia pastoris was first reported in this study. We cloned the
      DmAChE cDNA by reverse transcription PCR with removal of the signal for
      glycosylphosphatidylinositol (GPI) anchor attachment and the endogenous signal
      peptide coding sequence, and inserted it into P. pastoris vector pPIC9K under
      control of the alcohol oxidase gene AOX1 promoter (5'AOX1). The expression
      cassette of AChE cDNA was then introduced into methylotrophic yeast GS115 and
      several recombinant strains expressing R-DmAChE were obtained. The secreted R
      DmAChE showed high stability in neutral phosphate buffer at 4 degrees C, and its
      kinetic parameters were identical to those of the native DmAChE. The bimolecular
      rate constants of R-DmAChE to dichlorvos, aldicarb and carbaryl were ranging from
      three to six times higher than of native DmAChE. Within six insecticides, the R
      DmAChE was more sensitive than EeAChE, NbAChE and HuAChE. For 10 widely used
      insecticides, the IC50 values to the R-DmAChE were much lower than those to AChEs
      commonly used in China. With the R-DmAChE-based assay, samples spiked with three
      concentrations of pesticides caused enzymatic activity inhibition with R.S.D. of
      0-13.7%. These results suggest that the R-DmAChE can be useful for detection of
      organophosphate and carbamate insecticide residues.

PMID- 17222584
TI  - Comparisons of the allergenic mite prevalence in dwellings and certain outdoor
      environments of the Upper Silesia (southwest Poland).
AB  - The occurrence of allergenic mites (pyroglyphid house-dust mites, acarid and
      glycyphagid storage mites and others) in dwellings and in synanthropic outdoor
      sites in a densely populated urban area was investigated. A total of 335 house
      dust samples were collected from dwellings at 7 different locations in Upper
      Silesia (Poland), including 84 samples from dwellings of Katowice. Mites were
      found in 188 of the samples examined (56.1%). A total of 4410 mite specimens were
      isolated and identified, including 4212 members of the family Pyroglyphidae
      (95.51%). Among them, Dermatophagoides farinae was predominant (75.3%), followed
      by D. pteronyssinus (18.6%) and Euroglyphus maynei (1.5%). Moreover, litter
      soiled with communal wastes was sampled. All 86 samples contained mites. A total
      of 7547 mite specimens were isolated including 6050 mites known as allergenic
      (80.5%). Among the astigmatid mites two acarids were dominant: Tyrophagus
      silvester and T. longior (28.7% and 25.1% of all mites). It should be stressed
      that 6 of the acarid mite species or genera found in outdoor environments are
      typical domestic mites (T. putrescentiae), or they have been collected from house
      dust samples (T. longior, Tyrolichus casei, Thyreophagus entomophagus,
      Mycetoglyphus fungivorus and Rhizoglyphus robini). The litter of synanthropic
      sites can therefore form a substantial source of infestation.

PMID- 17222585
TI  - Autologous stem cells collected after debulking by high dose chemotherapy in late
      phase chronic myeloid leukemia may improve Imatinib efficacy.
AB  - The current curative therapeutic option for the treatment of chronic myeloid
      leukemia (CML) in the chronic phase is still allogeneic stem cell transplantation
      (SCT). For the patients who are not candidates for allogeneic SCT, Imatinib is
      the treatment of choice. It was found that high dose chemotherapy with autologous
      stem cell rescue prolongs the disease-free survival and may also restore
      sensitivity to interferon. Here we report the results of Imatinib treatment in
      three late-phase CML patients who were submitted to autologous SCT following
      resistance to interferon. Complete cytogenetic response and major molecular
      response were achieved in the three cases. Imatinib has the potential to induce
      late molecular remissions during the course of treatment and its effect may be
      optimized by a previous autologous SCT in this type of patients.

PMID- 17222586
TI  - Vascular endothelium summary statement VI: Research directions for the 21st
      century.
AB  - Effective translation of research advances from the bench to clinical and public
      health practice at the bedside and in the community at large represents an
      important step in the health research discovery enterprise. Increasingly, the gap
      in translating these advances into practice is being recognized. Successfully
      addressing this translational gap for the prevention and control of chronic
      diseases will require the development of novel, innovative, and, if necessary,
      nontraditional approaches. Participants in the 8th International Conference on
      Vascular Endothelium discussed a variety of novel approaches that have
      significant promise. Three of these approaches-vaccine development, genomics and
      proteomics, and tissue engineering-are highlighted in this position statement and
      strategies for public health practice and research are suggested.

PMID- 17222587
TI  - Complementary and alternative medicine in hepatology: review of the evidence of
      efficacy.
AB  - There is an increase in the use of complementary and alternative medicine (CAM),
      especially herbal therapy, among patients with liver disease. The most commonly
      used herbal agent is silymarin. In animal models, many of the commonly used
      agents have shown anti-inflammatory and antifibrotic effects. Although many human
      studies have shown improvements in subjective symptoms (well being) and liver
      biochemistry, there are no convincing data to suggest a definite histologic
      and/or virologic improvement with most of these agents. Poorly designed studies,
      heterogeneous patient populations, lack of standardized preparations, and poorly
      defined nonobjective end points may partly explain the conflicting reports in the
      literature. Hepatotoxicity and drug interactions are common with many herbal
      medications, and therefore physicians need to be cognizant of known or occult use
      of CAM by their patients. Only well-designed, randomized, controlled trials will
      be able to ascertain whether CAM has any role in the management of patients with
      acute or chronic liver diseases. Until such time, the use of CAM cannot be
      recommended as a therapy for patients with liver disease.

PMID- 17222588
TI  - Vitamin D and parathyroid hormone in outpatients with noncholestatic chronic
      liver disease.
AB  - BACKGROUND & AIMS: The liver plays a central role in vitamin D metabolism. Our
      aim was to determine the prevalence and type of vitamin D-parathyroid hormone
      (PTH) disturbance in ambulatory patients with noncholestatic chronic liver
      disease (CLD) and its relationship with disease severity and liver function.
      METHODS: We studied 100 consecutive outpatients (63 men, 37 women; mean age, 49.0
      +/- 12.1 [SD] y) with noncholestatic CLD caused by alcohol (n = 40), hepatitis C
      (n = 38), hepatitis B (n = 12), autoimmune hepatitis (n = 4), hemochromatosis (n
      = 4), and nonalcoholic steatohepatitis (n = 2); 51 patients had cirrhosis. Serum
      concentrations of 25-hydroxyvitamin D (25[OH]D), PTH, calcium, phosphate,
      magnesium, creatinine, and liver function tests were determined. RESULTS: Serum
      25(OH)D levels were inadequate in 91 patients: vitamin D deficiency (<50 nmol/L)
      was found in 68 patients and vitamin D insufficiency (50-80 nmol/L) was found in
      23 patients. Secondary hyperparathyroidism (serum PTH, >6.8 pmol/L) was present
      in 16 patients. The prevalence of vitamin D deficiency was significantly higher
      in cirrhotic vs noncirrhotic patients (86.3% vs 49.0%; P = .0001). In Child-Pugh
      class C patients, 25(OH)D levels were significantly lower than in class A
      patients (22.7 +/- 10.0 nmol/L vs 45.8 +/- 16.8 nmol/L; P < .001). Serum 25(OH)D
      independently correlated with international normalized ratio (negatively; P =
      .018) and serum albumin (positively; P = .007). Serum 25(OH)D levels of less than
      25 nmol/L predicted coagulopathy, hyperbilirubinemia, hypoalbuminemia, increased
      alkaline phosphatase, and anemia and thrombocytopenia. CONCLUSIONS: Vitamin D
      inadequacy is common in noncholestatic CLD and correlates with disease severity,
      but secondary hyperparathyroidism is relatively infrequent. Management of CLD
      should include assessment of vitamin D status in all patients and replacement
      when necessary.

PMID- 17222589
TI  - Major differences in the pulmonary circulation between birds and mammals.
AB  - The lungs of domestic chickens were perfused with blood or dextran/saline and the
      pulmonary artery pressure (P(a)) and venous pressure (P(v)) were varied in
      relation to air capillary pressure (P(A)). In Zone 3 conditions, pulmonary
      vascular resistance (PVR) was virtually unchanged with increases in either P(a)
      or P(v). This is very different behavior from mammals where the same
      interventions greatly reduce PVR. In Zone 2 conditions blood flow was essentially
      independent of P(v) as in mammalian lungs but all the capillaries appeared to be
      open, apparently incompatible with a Starling resistor mechanism. In Zone 1 the
      capillaries were open even when P(A) exceeded P(a) by over 30 cm H(2)O which is
      very different behavior from that of the mammalian lung. We conclude that the air
      capillaries that surround the blood capillaries provide rigid support in both
      compression and expansion of the vessels. The work suggests a pathogenesis for
      pulmonary hypertension syndrome in chickens which costs the broiler industry $1
      billion per year.

PMID- 17222590
TI  - The contribution of the pulmonary microvascular pressure in the maintenance of an
      open lung during mechanical ventilation.
AB  - Changes in pulmonary hemodynamics modify the mechanical properties of the lungs.
      The effects of alterations in pulmonary capillary pressure (Pc) were investigated
      on the airway and lung tissue mechanics during positive-pressure ventilation and
      following lung recruitment maneuvers. Isolated, mechanically normoventilated
      (PEEP 2.5 cmH(2)O) rat lungs were perfused with Pc set to 0 (unperfused), 5, 10
      or 15 mmHg, in random sequence. The pulmonary input impedance (ZL) was measured
      at end-expiration before and after a 10-min long ventilation. After inflation of
      the lung to 30 cmH(2)O during P-V curve recordings, another set of ZL was
      measured to evaluate the degree of recruitment. The PEEP was then decreased to
      0.5 cmH(2)O and the sequence was repeated. Airway resistance and parenchymal
      damping and elastance (H) were estimated from ZL by model fitting. From the P-V
      curves, elastance (E) and hysteresis indices were determined. Mechanical
      ventilation at both PEEP levels resulted primarily in elevations in the tissue
      parameters, with the greatest increases at the 0 Pc level (H changes of 27.8+/
      4.2 and 61.3+/-3.7% at 2.5 and 0.5 cmH(2)O PEEP, respectively). The maintenance
      of physiological Pc (10 mmHg) led to a significantly lower elevation in H (11.6+/
      1.5% versus 31.4+/-3.6%). The changes in the oscillatory mechanics were also
      reflected in E and the hysteresis of the P-V curves. These findings indicate that
      pulmonary hypoperfusion during mechanical ventilation forecasts a parenchymal
      mechanical deterioration. Physiological pressure in the pulmonary capillaries is
      therefore an important mechanical factor promoting maintenance of the stability
      of the alveolar architecture during positive-pressure mechanical ventilation.

PMID- 17222591
TI  - High performance liquid chromatography-electrospray ionization mass spectrometry
      (HPLC-MS/ESI) method for simultaneous determination of venlafaxine and its three
      metabolites in human plasma.
AB  - A high-performance liquid chromatography-electrospray ionization mass
      spectrometry (HPLC-MS/ESI) method for simultaneous determination of venlafaxine
      (VEN) and its three metabolites O-desmethylvenlafaxine (ODV), N
      desmethylvenlafaxine (NDV) and N,O-didesmethylvenlafaxine (DDV) in human plasma
      has been developed and validated. Estazolam was used as the internal standard.
      The compounds and internal standard were extracted from plasma by a liquid-liquid
      extraction. The HPLC separation of the analytes was performed on a Thermo BDS
      HYPERSIL C18 (250 mm x 4.6 mm, 5 microm, USA) column, using a gradient elution
      program with solvents constituted of water (ammonium acetate: 30 mmol/l, formic
      acid 2.6 mmol/l and trifluoroacetic acid 0.13 mmol/l) and acetonitrile (60:40,
      V/V) at a flow-rate of 1.0 ml/min. All of the analytes were eluted within 6 min.
      The compounds were ionized in the electrospray ionization (ESI) ion source of the
      mass spectrometer and were detected in the selected ion recording (SIR) mode.
      Calibration curves in spiked whole blood were linear from 4.0-700 ng/ml, 2.0-900
      ng/ml, 3.0-800 ng/ml and 2.0-700 ng/ml for VEN, ODV, NDV and DDV, respectively,
      all of them with coefficients of determination above 0.9991. The average
      extraction recoveries for all the four analytes were above 77%. The methodology
      recoveries were higher than 91%. The limits of detection were 0.4, 0.2, 0.3, and
      0.2 ng/ml for VEN, ODV, NDV and DDV, respectively. The intra- and inter-day
      variation coefficients were less than 11%. The method is accurate, sensitive and
      reliable for the pharmacokinetic study of venlafaxine as well as therapeutic drug
      monitoring (TDM).

PMID- 17222592
TI  - Protein glutathionylation and oxidative stress.
AB  - Liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS)
      demonstrated that glutathionyl hemoglobin (Hb) levels are increased in patients
      with diabetes, hyperlipidemia, uremia and Friedreich's ataxia. Glutathionylation
      of Hb is enhanced by oxidative stress. High performance liquid chromatography
      (HPLC) and matrix-assisted laser desorption ionization-time of flight mass
      spectrometry (MALDI-TOF-MS) have also been developed for the quantification of
      glutathionyl Hb. Glutathionyl-lens proteins were detected in uremic patients and
      cataractous aged subjects. Glutathionylation of numerous enzymes is induced by
      oxidative stress, reduces their catalytic activities and may be involved in
      protection from the damaging effects of oxidative agents. Thioredoxin,
      glutaredoxin (thioltransferase) and protein disulfide isomerase are the key
      enzymes in controlling cellular oxidative stress that catalyze reduction of
      glutathionyl protein disulfide bonds. Thus, protein glutathionylation is closely
      associated with oxidative stress.

PMID- 17222593
TI  - The biological standard of living (and its convergence) in Colombia, 1870-2003. A
      tropical success story.
AB  - During the 20th century, the evolution of the biological standard of living in
      Colombia was a tropical success story from the point of view of the secular
      increase in height as well as the reduction of inequality. During the period 1905
      1985 the average height of females and males increased by nearly 9 cm on the
      basis of 9 million records examined from National Identification Cards. We also
      study the evolution of height of Colombians on the basis of passport records. The
      elite group of passport holders was much taller than average, and remained stable
      for the birth cohorts of 1870-1919. In the early 20th century the height of
      passport recipients was 168.7 cm (men) and 158 cm (women) compared with 162 cm
      and 150 cm for heights in the national ID cards. The results also show that
      Colombians experienced significant regional and intrapersonal convergence in
      height.

PMID- 17222597
TI  - Volunteerism and humanitarian efforts in surgery.

PMID- 17222594
TI  - Glutamate 2,3-aminomutase: a new member of the radical SAM superfamily of
      enzymes.
AB  - A gene eam in Clostridium difficile encodes a protein that is homologous to
      lysine 2,3-aminomutase (LAM) in many other species but does not have the lysyl
      binding residues Asp293 and Asp330 in LAM from Clostridium subterminale SB4. The
      C. difficile protein has Lys and Asn, respectively, in the sequence positions of
      the essential Asp residues in LAM. The C. difficile gene has been cloned into an
      E. coli expression vector, expressed in E. coli, and the protein purified and
      characterized. The recombinant protein displays excellent activity as a glutamate
      2,3-aminomutase and no activity toward l-lysine. The PLP-, iron-, and sulfide
      content and ultraviolet/visible spectrum are similar to LAM, and the enzyme
      requires SAM and dithionite as activators, as does LAM. Freeze-quench EPR
      experiments in the presence of l-glutamate reveal a glutamate-based free radical
      in the steady state of the reaction. A number of other bacterial genomes include
      genes encoding proteins homologous to the glutamate 2,3-aminomutase from C.
      difficile, and four of these proteins display the activity of glutamate 2,3
      aminomutase when produced in E. coli. All of the homologous proteins have the
      cysteine motif CSMYCRHC corresponding to the motif CxxxCxxC characteristic of
      radical SAM enzymes. It is concluded that glutamate 2,3-aminomutase from C.
      difficile is a representative of a family found in a number of bacteria. It is
      likely that the beta-glutamate found in a few bacterial and archeal species as an
      osmolyte arises from the action of glutamate 2,3-aminomutase.

PMID- 17222601
TI  - Pursuit of a paradigm for professional progress.

PMID- 17222602
TI  - Understanding mixed messages about prostate specific antigen: biases in the
      evaluation of cancer biomarkers.

PMID- 17222603
TI  - SELECTing the best.

PMID- 17222604
TI  - Grading systems in renal cell carcinoma.
AB  - PURPOSE: We reviewed updated literature data concerning several issues of renal
      cell carcinoma grading systems. MATERIALS AND METHODS: We performed a
      nonsystematic review of the literature. Data were identified by a MEDLINE search
      using a strategy including MeSH and free text protocols. From the MEDLINE search
      we collected 184 records. RESULTS: Although the original study was published in
      1982, the independent predictive value of nuclear grades was only revealed in
      2000 by the team from University of California-Los Angeles. Subsequently further
      data from our group and the group at the Mayo Clinic reconfirmed those findings,
      although similar cancer specific survival probabilities were noted among
      different grades. The prognostic relevance of nuclear grade justified the
      inclusion of that variable in algorithms and nomograms predictive of cancer
      specific survival, such as those provided by University of California-Los
      Angeles, the Mayo Clinic and Memorial Sloan-Kettering Cancer Center. Despite the
      routine clinical use of nuclear grade, several drawbacks have affected grading
      systems, such as interobserver and intra-observer reproducibility, and
      variability of the cancer specific survival probabilities stratified by grade.
      Several studies showed that intra-observer and interobserver agreement with
      regard to grade are only moderate with up shifting in all series. That issue
      might be due to the heterogeneity of renal cell carcinoma as well as to the lack
      of consensus about the minimal size of high grade tumor to be considered
      significant. Moreover, recent data underscore the role of histological subtypes.
      CONCLUSIONS: Grade is one of the most powerful prognostic factors in patients
      with renal cell carcinoma. The Fuhrman grading system is currently most widely
      used by pathologists in Europe and the United States. However, there is still a
      need for better standardization of nuclear criteria to improve interobserver
      reproducibility and a major consensus should be achieved by uropathologists.

PMID- 17222605
TI  - Defining optimal therapy for muscle invasive bladder cancer.
AB  - PURPOSE: We defined an optimal curative strategy for muscle invasive bladder
      cancer and to determine how best to deliver curative therapy. MATERIALS AND
      METHODS: We reviewed published reports from 1985 to 2006 dealing with the
      treatment of muscle invasive (stage T2-T4a) bladder cancer. We analyzed all
      cohort, phase II and randomized phase III studies providing level 1 to 3 evidence
      impacting survival. RESULTS: Cisplatin based chemotherapy combined with high
      quality radical cystectomy and complete pelvic lymph node dissection improves
      survival over that of cystectomy alone. Surgery quality is an important predictor
      of survival even in patients receiving chemotherapy. Neoadjuvant chemotherapy is
      favored over adjuvant chemotherapy because it is better tolerated and more
      patients are able to receive effective therapy before rather than after surgery.
      CONCLUSIONS: Neoadjuvant chemotherapy followed by radical cystectomy and complete
      pelvic lymph node dissection is the optimal curative strategy in most patients
      presenting with muscle invasive bladder cancer.

PMID- 17222606
TI  - Epidemiology and pathophysiology of prostate cancer in African-American men.
AB  - PURPOSE: Along with increasing age and a positive family history subSaharan
      African ancestry has long been recognized as an important risk factor for
      prostate cancer. In the United States the incidence of prostate cancer is
      approximately 60% higher in African-American than in European-American men and
      the mortality rate from the disease is more than twice as high. The purpose of
      this review article is to examine specific reports highlighting racial disparity
      and its possible causes. MATERIALS AND METHODS: The reports chosen for review of
      this epidemiology and pathophysiology study were included to demonstrate
      conditions in which racial differences as well as similarities exist in African
      American and European-American men. Reports also include autopsy, biological and
      clinical studies, and early and late stage prostate cancer. RESULTS: From the
      1970s to the current statistical analysis of the National Cancer Institute
      Surveillance, Epidemiology, and End Results program African-American men have
      continued to have a significant higher incidence and mortality rate than European
      American men. Autopsy studies show a similar prevalence of early small
      subclinical prostate cancers but a higher prevalence of high grade prostatic
      intraepithelial neoplasia. Clinical studies show a similarity in prostate cancer
      outcome when pathological stage is organ confined but a worse outcome when
      disease is locally advanced and metastatic in African-American vs European
      American men. There is increasing genetic evidence that suggest that prostate
      cancer in African-American vs European-American men may be more aggressive,
      especially in young men. CONCLUSIONS: Improving the outcome in African-American
      men with prostate cancer requires awareness of the epidemiological patterns of
      the disease and willingness on the part of physicians to implement targeted study
      initiatives with end points designed to detect the disease early in this
      population and begin appropriate management. It is proposed that a multi
      institutional study should be done to demonstrate the ability to decrease racial
      outcome disparity by education, aggressive testing and treatment.

PMID- 17222607
TI  - Symptoms of interstitial cystitis, painful bladder syndrome and similar diseases
      in women: a systematic review.
AB  - PURPOSE: In women symptoms of interstitial cystitis are difficult to distinguish
      from those of painful bladder syndrome and they appear to overlap with those of
      urinary tract infection, chronic urethral syndrome, overactive bladder,
      vulvodynia and endometriosis. This has led to difficulties in formulating a case
      definition for interstitial cystitis, and complications in the treatment and
      evaluation of its impact on the lives of women. We performed a systematic
      literature review to determine how best to distinguish interstitial cystitis from
      related conditions. MATERIALS AND METHODS: We performed comprehensive literature
      searches using the terms diagnosis, and each of interstitial cystitis, painful
      bladder syndrome, urinary tract infection, overactive bladder, chronic urethral
      syndrome, vulvodynia and endometriosis. RESULTS: Of 2,680 screened titles 604
      articles were read in full. The most commonly reported interstitial cystitis
      symptoms were bladder/pelvic pain, urgency, frequency and nocturia. Interstitial
      cystitis and painful bladder syndrome share the same cluster of symptoms. Chronic
      urethral syndrome is an outdated term. Self-reports regarding symptoms and
      effective antibiotic use can distinguish recurrent urinary tract infections from
      interstitial cystitis in some but not all women. Urine cultures may also be
      necessary. Pain distinguishes interstitial cystitis from overactive bladder and
      vulvar pain may distinguish vulvodynia from interstitial cystitis. Dysmenorrhea
      distinguishes endometriosis from interstitial cystitis, although many women have
      endometriosis plus interstitial cystitis. CONCLUSIONS: In terms of symptoms
      interstitial cystitis and painful bladder syndrome may be the same entity.
      Recurrent urinary tract infections may be distinguished from interstitial
      cystitis and painful bladder syndrome via a combination of self-report and urine
      culture information. Interstitial cystitis and painful bladder syndrome may be
      distinguished from overactive bladder, vulvodynia and endometriosis, although
      identifying interstitial cystitis and painful bladder syndrome in women with more
      than 1 of these diseases may be difficult.

PMID- 17222608
TI  - Ignorance is bliss: the Listerian revolution and education of American surgeons.
AB  - PURPOSE: Joseph Lister introduced antiseptic surgery in 1867. American surgeons,
      entrenched in the old ways of 19th century medicine, failed to adopt Lister's
      methods. MATERIALS AND METHODS: Examples of the hubris and arrogant thinking
      displayed by early American surgeons are best shown by Thomas Eakins'
      masterpiece, The Gross Clinic, and by the death of President James Garfield.
      RESULTS: Samuel Gross, preeminent American surgeon in 1875 boldly revealed in The
      Gross Clinic, and the team of distinguished surgeons using outdated methods
      caring for Garfield in 1881, illustrate American surgeons' woeful disdain and
      disregard of sterile surgical methods. CONCLUSIONS: Public outcry over the
      failure of some of America's best surgeons led to widespread adoption of
      antiseptic surgery by the late 1880s and introduction of basic science into the
      medical education by the dawn of the new century.

PMID- 17222609
TI  - Familial renal carcinoma: clinical evaluation, clinical subtypes and risk of
      renal carcinoma development.
AB  - PURPOSE: Familial renal carcinoma is defined as families with 2 or more
      individuals with renal cell carcinoma without evidence of known hereditary renal
      carcinoma syndromes. To better characterize this familial cancer we reviewed
      renal carcinoma families evaluated at the National Cancer Institute between 1990
      and 2004 to identify distinctive features of these families. We also determined
      the risk of renal carcinoma in first-degree relatives of affected family members.
      MATERIALS AND METHODS: We evaluated 141 at risk asymptomatic relatives of
      affected individuals from 50 families with 2 or more members with renal
      carcinoma. Histology slides of renal tumors from affected family members were
      reviewed. At risk members from renal carcinoma families were screened for occult
      renal neoplasms by renal ultrasound and computerized tomography. DNA from select
      families was tested for germline mutations of known renal carcinoma genes when
      clinically indicated and constitutional cytogenetic analysis was performed to
      search for germline chromosome alterations. RESULTS: Familial renal carcinoma
      families could be subdivided into subtypes based on tumor multiplicity and renal
      tumor histology. Of 141 at risk members of renal carcinoma families screened for
      occult renal tumors 2 were found to have occult renal tumors, which were
      identified as renal oncocytoma and a solid tumor that was not resected,
      respectively. No histologically confirmed occult renal carcinomas were detected
      in at risk family members. Several families previously classified as having
      familial renal carcinoma were found on further evaluation to have hereditary
      renal cancer syndromes. CONCLUSIONS: Familial renal carcinoma is a heterogeneous
      clinical and pathological entity. Familial renal carcinoma was subdivided into
      groups based on tumor multiplicity and tumor pathology. The empirical risk of
      histologically documented renal carcinoma in first-degree relatives who were
      members of familial renal carcinoma families was less than 1:141. One renal
      oncocytoma and 1 small solid renal tumor were detected.

PMID- 17222611
TI  - Watchful waiting for solid renal masses: insight into the natural history and
      results of delayed intervention.
AB  - PURPOSE: We describe the short-term outcomes of patients whose renal masses were
      managed expectantly (ie watchful waiting) to provide insight into the natural
      history of small renal tumors. Additionally, this study examined the effects of
      delayed intervention in patients who required intervention after a period of
      expectant management. MATERIALS AND METHODS: A total of 43 patients with 46 renal
      masses underwent planned expectant management of enhancing solid or cystic
      (Bosniak IV) renal masses. A subset of these patients (13) who underwent eventual
      intervention was also examined. Outcomes with regard to age, gender, growth rate,
      subsequent interventions and clinical followup are reported. RESULTS: At a mean
      followup of 36 months 74% of patients had tumor growth with a mean (median)
      growth rate of 0.70 (0.35) cm per year. None of the patients had significant
      symptoms, disease progression or cancer specific death. There were 4 patients
      (10%) who died of other causes. The 13 patients undergoing eventual intervention
      were younger than those who did not undergo intervention (56 vs 72 years,
      respectively, p = 0.0006). Patients undergoing eventual intervention tended to
      have a higher tumor growth rate than those on continued observation (0.90 vs 0.61
      cm per year, respectively, p = 0.1486). In patients undergoing eventual
      intervention 12 of 14 (87%) tumors were renal cell carcinoma. All were stage pT1,
      and 12 of 13 patients were alive after a mean followup of 41 months (1 patient
      died of other causes 30 months after surgery). No patient had up-staging of
      disease secondary to delay. CONCLUSIONS: Watchful waiting for renal masses is a
      reasonable option for appropriately selected patients, especially those with
      competing comorbidities. Delayed intervention does not appear to adversely impact
      pathological outcomes.

PMID- 17222613
TI  - The impact of ischemia time during open nephron sparing surgery on solitary
      kidneys: a multi-institutional study.
AB  - PURPOSE: The safe duration of ischemia during nephron sparing surgery remains
      controversial. We performed a multi-institutional study to evaluate the renal
      effects of vascular clamping in patients with solitary kidneys. MATERIALS AND
      METHODS: Using the Cleveland Clinic and Mayo Clinic databases, we identified 537
      patients with solitary kidneys who underwent open nephron sparing surgery. Renal
      complications were compared among patients who did not require vascular clamping
      (85), and those who had warm ischemia (174) and cold ischemia (278). RESULTS:
      Median patient age (63, 65, 64 years) and preoperative creatinine (1.4, 1.3, 1.4
      mg/dl) were similar among patients with no ischemia, warm ischemia and cold
      ischemia, respectively. Median tumor size was smaller in patients with no
      ischemia (2.5 cm), compared to patients with warm (3.5 cm) and cold (4.0 cm)
      ischemia (p <0.001). Warm and cold ischemia was associated with a significantly
      increased risk of urine leak (p = 0.006), acute (p <0.001) and chronic (p =
      0.027) renal failure, and temporary dialysis (p = 0.028) compared to patients
      with no ischemia. Warm ischemia longer than 20 minutes and cold ischemia longer
      than 35 minutes were associated with a higher incidence of acute renal failure (p
      = 0.002 and p = 0.003, respectively). Additionally, warm ischemia more than 20
      minutes was associated with an increased risk of chronic renal insufficiency (41%
      vs 19%, p = 0.008), increase in creatinine greater than 0.5 (42% vs 15%, p
      <0.001) and permanent dialysis (10% vs 4%, p = 0.145). CONCLUSIONS: Vascular
      clamping during open nephron sparing surgery is associated with a higher
      incidence of renal complications. Attempts to limit warm ischemia to 20 minutes
      and cold ischemia to 35 minutes should be used when vascular clamping is
      necessary.

PMID- 17222614
TI  - Dynamic outcome prediction in patients with clear cell renal cell carcinoma
      treated with radical nephrectomy: the D-SSIGN score.
AB  - PURPOSE: To date all prediction models for patients with renal cell carcinoma
      have estimated outcome in static fashion starting from the date of surgery only.
      We created a dynamic outcome prediction model for continual surveillance that
      accounts for the disease-free interval following surgery. MATERIALS AND METHODS:
      We identified 1,560 patients treated with radical nephrectomy for pM0 clear cell
      renal cell carcinoma between 1970 and 1999. The previously published stage, size,
      grade and necrosis score was used to stratify patients according to the risk of
      death from renal cell carcinoma. Cancer specific survival rates were calculated
      using the Kaplan-Meier method at surgery and at various disease-free intervals
      following surgery. RESULTS: At last followup 461 of the 1,560 patients had died
      of renal cell carcinoma at a median of 3.1 years following surgery. Median
      followup in patients still alive was 11.2 years. Patient outcome improved as the
      disease-free interval following surgery increased. For example, patients with a
      stage, size, grade and necrosis score of 5 had an estimated 5-year cancer
      specific survival rate of 69.6% at surgery. However, those who survived without
      disease for 1, 2 and 3 years following surgery had adjusted estimated 5-year
      cancer specific survival rates of 81.9%, 91.9% and 93.2%, respectively. Patients
      with a stage, size, grade and necrosis score of 7 had a 5-year cancer specific
      survival rate of 44.9% at surgery, which increased to 63.3%, 71.0% and 72.8%
      after 1 to 3 years of disease-free followup, respectively. CONCLUSIONS: Within
      each stage, size, grade and necrosis score cancer specific survival rates
      increase as the disease-free interval following surgery increases. We present a
      dynamic outcome prediction model that allows clinicians to continually adjust
      surveillance as the disease-free interval increases.

PMID- 17222615
TI  - Predictive value of cell cycle biomarkers in nonmuscle invasive bladder
      transitional cell carcinoma.
AB  - PURPOSE: We determined whether the combined expression of p53, p21, p27 and pRB
      is associated with outcomes of patients with nonmuscle invasive bladder
      transitional cell carcinoma. MATERIALS AND METHODS: Immunohistochemical staining
      for p53, p21, p27 and pRB was performed on archival bladder specimens from 9
      normal controls and 74 patients who underwent transurethral bladder tumor
      resection for Ta, Tis and/or T1 transitional cell carcinoma. RESULTS: Normal
      urothelium had wild type status of p53, pRB, p21 and p27. p53 expression was
      altered in 34% of patients with transitional cell carcinoma, pRB in 39%, p21 in
      35% and p27 in 47%. When analyzed separately, p53, pRB and p21 were each
      independently associated with tumor progression. Combination of biomarkers
      stratified patients into statistically significantly different risk groups for
      disease recurrence and progression. When tumor stage and grade were modeled with
      all 4 biomarkers, p53 and p27 were the sole independent predictors of disease
      recurrence and progression. After controlling for the effects of tumor grade and
      stage, the incremental number of altered biomarkers was associated with an
      increased risk of bladder cancer recurrence (p for trend = 0.011) and progression
      (p for trend = 0.005). The risk ratio for disease recurrence and progression
      increased incrementally with the number of biomarkers altered. CONCLUSIONS:
      Combinations of p53, pRB, p21 and p27 had cooperative/synergistic effects
      stratifying patients into different risk groups. Higher total numbers of altered
      biomarkers were independently associated with an increased risk of disease
      progression and death. Prospective trials are necessary to usher bladder cancer
      management into the age of molecular biomarkers.

PMID- 17222617
TI  - Relationship between body mass index and prostate cancer screening in the United
      States.
AB  - PURPOSE: Obesity is associated with more advanced disease and worse outcomes in
      men with prostate cancer. To our knowledge the relationship between obesity and
      prostate cancer screening behavior in men 40 or older is unknown. Thus, we
      examined associations between body mass index and prostate cancer screening
      behavior. MATERIALS AND METHODS: We used the 2002 Behavioral Risk Factor
      Surveillance System to study prostate cancer screening in a representative sample
      of 57,827 men 40 years or older. Primary outcomes were the proportion of men ever
      screened and the proportion screened in the last year for prostate cancer.
      RESULTS: Obese men were more likely than normal weight men to have had a prostate
      specific antigen test (62.1% vs 56.1%, p <0.001) and to have had a prostate
      specific antigen test in the last year (44.2% vs 38.2%, p <0.001). After
      controlling for sociodemographic characteristics obese men remained more likely
      than normal weight men to have had a prostate specific antigen test (OR 1.46, 95%
      CI 1.33-1.61) and to have had a prostate specific antigen test in the last year
      (OR 1.42, 95% CI 1.30-1.55). Respondents reporting an ongoing relationship with a
      physician (OR 2.88, 95% CI 2.57-3.22) and black nonHispanic men vs white men (OR
      1.58, 95% CI 1.38-1.81) were also more likely to have had a prostate specific
      antigen test in the last year. CONCLUSIONS: Obese men are more likely than normal
      weight men to be screened for prostate cancer. Associations between advanced
      stage, worse outcomes and obesity may not be explained by disparities in the
      screening of obese men for prostate cancer.

PMID- 17222618
TI  - Age adjusted prostate specific antigen and prostate specific antigen velocity cut
      points in prostate cancer screening.
AB  - PURPOSE: We identified age adjusted prostate specific antigen and prostate
      specific antigen velocity cut points for prostate cancer biopsy. MATERIALS AND
      METHODS: A cohort of 33,643 men was retrieved from the Duke Prostate Center
      database. Of this group 11,861 men with 2 or more prostate specific antigen
      values within 2 years were analyzed for age adjusted prostate specific antigen
      and prostate specific antigen velocity performance in cancer risk assessment
      using a receiver operating characteristic curve. RESULTS: In the 11,861 men
      prostate cancer prevalence was 273 (8.0%), 659 (14.9%) and 722 (17.9%) in the
      groups of men 50 to 59 years old, 60 to 69 and 70 years old or older. In prostate
      cancer groups median prostate specific antigen and prostate specific antigen
      velocity in men 50 to 59 vs 70 years old or older were 5.6 vs 8.1 ng/ml and 1.37
      vs 1.89 ng/ml per year (<0.0001). In men 50 to 59 years old the sensitivity and
      specificity were 82.1% and 80.7% at prostate specific antigen 2.5 ng/ml, and
      84.3% and 72.4% at prostate specific antigen velocity 0.40 ng/ml per year, higher
      than those in men 70 years old or older at prostate specific antigen 4.0 ng/ml or
      prostate specific antigen velocity 0.75 ng/ml per year. Decreasing the prostate
      specific antigen cut point to 2.0 ng/ml and the prostate specific antigen
      velocity cut point to 0.40 ng/ml per year in men 50 to 59 years old improved the
      cancer detection rate but decreased the positive predictive value. CONCLUSIONS:
      Current biopsy guidelines (prostate specific antigen 4.0 ng/ml or greater, or
      prostate specific antigen velocity 0.75 ng/ml or greater per year) underestimated
      cancer risk in men 50 to 59 years old. Prostate specific antigen and prostate
      specific antigen velocity cut points should be age adjusted. In men 50 to 59
      years old prostate specific antigen and prostate specific antigen velocity cut
      points could be decreased to 2.0 ng/ml and 0.40 ng/ml per year, respectively.
      Factors of age, sensitivity, specificity, positive predictive value and cancer
      prevalence are critical for obtaining the desired balance between cancer
      detection and negative biopsy.

PMID- 17222621
TI  - Prostate specific antigen density correlates with features of prostate cancer
      aggressiveness.
AB  - PURPOSE: An increased prostate specific antigen density (serum prostate specific
      antigen divided by prostate volume) is an established parameter to help determine
      the need to perform prostate biopsies. A man with a high prostate specific
      antigen and a normal size prostate gland is more likely to have cancer than a man
      with the same prostate specific antigen and a large gland. Prostate specific
      antigen in relation to prostate size should also reflect the volume of cancer in
      the gland. One group defined clinically unimportant prostate cancer as tumor
      volume less than 0.5 cc, organ confined disease and Gleason less than 7. Another
      group noted that at the time of biopsy, a prostate specific antigen density less
      than 0.15 ng/ml/cc combined with low risk clinical tumor features predicted
      insignificant cancer. There are limited published validating data on the
      association of prostate specific antigen density with the criteria for prostate
      cancer aggressiveness. We tested the association of prostate specific antigen
      density with features of tumor aggressiveness in a screened and in a nonscreened
      cohort of patients with clinically localized prostate cancer treated with radical
      prostatectomy. MATERIALS AND METHODS: The screened patient cohort included 1,280
      patients with screen detected prostate cancer treated from 1990 to 2002 at
      Washington University, and the nonscreened cohort included 382 patients treated
      from 2003 to 2004 at Northwestern University. We recorded the clinical and
      pathological tumor parameters in a prospective database. Parameters evaluated
      were pathological tumor stage, Gleason sum, tumor volume, biochemical progression
      and the previously mentioned 2 criteria for clinically unimportant cancers. We
      grouped patients into 4 prostate specific antigen density categories of less than
      0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc. RESULTS: There was
      a significant trend for worsening clinicopathological prognostic features as
      prostate specific antigen density increased. There were 357 (82%), 283 (75%), 171
      (75%) and 192 (55%) men with organ confined disease with clear surgical margins
      if prostate specific antigen density was less than 0.1, 0.1 to 0.14, 0.15 to 0.19
      and greater than 0.19 ng/ml/cc, respectively (p <0.001). There were 86 (20%), 102
      (27%), 64 (28%) and 157 (45%) men with a Gleason sum greater than 7 when grouped
      into each increasing PSA density category, respectively (p <0.001). There were 91
      (21%), 91 (25%), 74 (33%) and 157 (46%) men with a total cancer volume greater
      than 0.5 cc when grouped into each increasing PSA density category, respectively
      (p <0.001). Prostate specific antigen velocity was greater than 2 ng/ml per year
      in 11%, 30%, 27% and 46% of men if prostate specific antigen density was less
      than 0.1, 0.1 to 0.14, 0.15 to 0.19 and greater than 0.19 ng/ml/cc, respectively
      (p <0.001). CONCLUSIONS: Prostate specific antigen density measurements are
      useful in helping to determine the aggressiveness of clinically localized
      prostate cancer, and can be used as an adjunct in predicting insignificant cancer
      and outcomes after local therapy.

PMID- 17222622
TI  - Development and external validation of an extended repeat biopsy nomogram.
AB  - PURPOSE: We hypothesized that the outcome of repeat biopsy could be accurately
      predicted. We tested this hypothesis in a contemporary cohort from 3 centers.
      MATERIALS AND METHODS: The principal cohort of 1,082 men from Hamburg, Germany
      was used for nomogram development as well as for internal 200 bootstrap
      validation in 721 and external validation in 361. Two additional external
      validation cohorts, including 87 men from Milan, Italy and 142 from Seattle,
      Washington, were also used. Predictors of prostate cancer on repeat biopsy were
      patient age, digital rectal examination, prostate specific antigen, percent free
      prostate specific antigen, number of previous negative biopsy sessions and
      sampling density. Multivariate logistic regression models were used to develop
      the nomograms. RESULTS: The mean number of previous negative biopsies was 1.5
      (range 1 to 6) and the mean number of cores at final repeat biopsy was 11.1
      (range 10 to 24). Of the men 370 (30.2%) had prostate cancer. On multivariate
      analyses all predictors were statistically significant (p < or =0.028). After
      internal validation the nomogram was 76% accurate. External validation showed 74%
      (Hamburg), 78% (Milan) and 68% (Seattle) accuracy. CONCLUSIONS: Relative to the
      previous nomograms (10 predictors or 71% accuracy) our tool relies on fewer
      variables (6) and shows superior accuracy in European men. Accuracy in American
      men is substantially lower. Racial, clinical and biochemical differences may
      explain the observed discrepancy in predictive accuracy.

PMID- 17222623
TI  - The continuing importance of transrectal ultrasound identification of prostatic
      lesions.
AB  - PURPOSE: In light of a recent tendency toward systematic nontargeted biopsy we
      reassessed whether identification and biopsy of ultrasonographically suspicious
      lesions contribute to the detection of prostate cancer. MATERIALS AND METHODS: We
      reviewed prospectively gathered data on 7,426 transrectal ultrasound directed
      prostatic biopsies performed at our institution between June 16, 2000 and
      September 1, 2005. Patients underwent systematic biopsy (6 to 10 cores on initial
      biopsy and 13 to 15 on rebiopsy) with additional sampling of visible suspicious
      lesions. The RR for finding cancer in transrectal ultrasound positive and
      negative patients was calculated for likely independent prognostic variables.
      RESULTS: A total of 3,828 biopsies (51.5%) were transrectal ultrasound negative
      and 3,598 (48.5%) were transrectal ultrasound positive. Prostate cancer was
      detected in 3,258 biopsies (43.9%). For each independent variable the RR for
      prostate cancer was higher if a sonographic lesion was present. A lesion
      increased the likelihood of cancer detection (57.8% vs 30.8%, RR 1.8). Biopsies
      from lesions identified by transrectal ultrasound had a greater median percent of
      the core involved with cancer (50% vs 10%, p <0.001) and they were more likely to
      have Gleason score 7 or greater (69.3% vs 28.3%, p <0.001). CONCLUSIONS: Biopsies
      taken when a prostatic lesion is identified by transrectal ultrasound are almost
      twice as likely to show cancer than when no lesion is visible. These cancers are
      of higher grade and volume and, therefore, they are more clinically significant.
      The search for and targeted biopsy of suspicious lesions seen on transrectal
      ultrasound remains important for prostate cancer diagnosis.

PMID- 17222624
TI  - The anterior layer of Denonvilliers' fascia: a common misconception in the
      laparoscopic prostatectomy literature.
AB  - PURPOSE: Incision of the anterior layer of Denonvilliers' fascia is commonly
      cited as a key step in successful dissection of the vasa deferentia and seminal
      vesicles from the posterior bladder neck during laparoscopic radical
      prostatectomy. However, anatomical descriptions do not support the presence of
      Denonvilliers' fascia anterior to the seminal vesicles. To address this
      inconsistency we performed a detailed anatomical study of tissue planes
      encountered during laparoscopic dissection of the posterior bladder neck.
      MATERIALS AND METHODS: To grossly characterize the tissue planes encountered
      during laparoscopic posterior bladder neck dissection, ex vivo dissections were
      performed on 4 separate cystoprostatectomy specimens. Biopsies of the
      representative areas were obtained from 20 consecutive laparoscopic radical
      prostatectomy specimens by 2 dedicated uropathologists. RESULTS: Following
      incision into the posterior bladder neck mucosa, longitudinally oriented fibers
      were readily visualized, extending from bladder neck to prostate base.
      Histologically this anatomical landmark represents the fusion of 2 separate
      tissue layers, that is an inner lamella composed of longitudinally disposed
      smooth muscle fibers in continuation with the longitudinal fascia of the bladder
      detrusor (medial fascicle of the detrusor running in between the ureters) and an
      outer lamella composed of fibroadipose tissue in continuation with the bladder
      adventitia. CONCLUSIONS: Our anatomical and histological analysis refutes the
      prevailing belief in the laparoscopic literature that the longitudinal muscle
      fibers identified during dissection of the posterior bladder neck represent the
      anterior layer of Denonvilliers' fascia. They correspond to the posterior
      longitudinal fascia of the detrusor muscle that is externally upholstered by the
      bladder adventitia.

PMID- 17222625
TI  - Limited pelvic lymph node dissection at the time of radical prostatectomy does
      not affect 5-year failure rates for low, intermediate and high risk prostate
      cancer: results from CaPSURE.
AB  - PURPOSE: Limited bilateral pelvic lymph node dissection performed at radical
      prostatectomy provides staging information that is used to guide further disease
      management. Given the effects of widespread prostate specific antigen testing and
      stage migration, most procedures in the United States are performed for low risk
      disease, which has a low probability (less than 1%) of lymph node metastasis. We
      compared 5-year treatment failure rates in patients with low, intermediate and
      high risk disease who underwent radical prostatectomy with or without pelvic
      lymph node dissection. MATERIALS AND METHODS: We compared treatment failure rates
      for radical prostatectomy in 4,693 patients enrolled in the CaPSURE database who
      underwent radical prostatectomy with or without limited pelvic lymph node
      dissection. Secondary analysis was performed as a function of pelvic lymph node
      dissection and risk group based on pretreatment stage, grade and prostate
      specific antigen. Treatment failure rates were estimated by Kaplan-Meier
      analysis. RESULTS: The 5-year failure-free survival rate was 70% in the no pelvic
      lymph node dissection group and 74% in the limited pelvic lymph node dissection
      group (p = 0.11), while the rates in the low, intermediate and high risk groups
      were 81% and 82% (p = 0.83), 71% and 63% (p = 0.21), and 42% and 48% (p = 0.45)
      in the no vs limited pelvic lymph node dissection groups, respectively.
      Multivariate analysis demonstrated that pelvic lymph node dissection status was
      not a predictor of treatment failure (p = 0.93). CONCLUSIONS: This study
      demonstrates in a large cohort of patients that limited pelvic lymph node
      dissection at radical prostatectomy has no effect on treatment failure rates at 5
      years in those at low, intermediate and high risk.

PMID- 17222627
TI  - The impact of prior radical prostatectomy in men with metastatic castration
      recurrent prostate cancer: a pooled analysis of 9 Cancer and Leukemia Group B
      Trials.
AB  - PURPOSE: A prior report suggested that radical prostatectomy may confer a
      survival advantage to patients with metastatic castration recurrent prostate
      cancer. Therefore, a pooled analysis of 9 trials performed by Cancer and Leukemia
      Group B was done to determine if men with metastatic castration recurrent
      prostate cancer who underwent prior prostatectomy had improved clinical outcomes,
      such as overall, prostate specific, progression-free and PSA progression-free
      survival, than men who did not undergo prior prostatectomy. MATERIALS AND
      METHODS: Data from 9 multi-institutional trials performed by Cancer and Leukemia
      Group B were combined. Eligible patients had progressive prostate cancer during
      androgen deprivation therapy, Eastern Cooperative Oncology Group performance
      status 0-2, and adequate hematological, renal and hepatic functions. The
      proportional hazards model was used to assess the prognostic importance of
      radical prostatectomy for predicting clinical outcomes. RESULTS: Of 1,238 men 310
      (25%) underwent prostatectomy. Median survival was 14.7 (95% CI 12.9-16.7) and
      14.5 months (95% CI 13.5-15.7) in men who did and did not undergo prostatectomy,
      respectively. The HR for death was 1.03 (95% CI 0.90-1.19, p = 0.65) in men with
      vs without prostatectomy. CONCLUSIONS: Prior prostatectomy in men with metastatic
      castration recurrent prostate cancer who were subsequently enrolled on clinical
      trials for cancer treatment had similar survival compared to men who did not
      undergo prior prostatectomy. These data do not support another report suggesting
      that prior prostatectomy confers a subsequent survival advantage in men with
      castration recurrent prostate cancer.

PMID- 17222628
TI  - Population based study of hormonal therapy and survival in men with metastatic
      prostate cancer.
AB  - PURPOSE: Although the palliative benefits of hormonal therapy for metastatic
      prostate cancer are widely recognized, little information is available regarding
      the effect of hormonal therapy on cancer specific and overall survival, and the
      types of patients who might benefit the most or least from hormonal therapy.
      MATERIALS AND METHODS: Prostate cancer specific and overall survival according to
      hormonal therapy use was determined by the Kaplan-Meier method in 6,098 men 65
      years or older diagnosed with metastatic prostate cancer in 1991 to 1999 who were
      identified through the population based Surveillance, Epidemiology, and End
      Results, and Medicare linked database. Cox proportional hazards and propensity
      score methods were used to adjust for potential confounders, such as disease
      status and patient comorbidity. RESULTS: Propensity score adjusted median overall
      survival was 26 months in men who received hormonal therapy compared with 13
      months in those who did not (HR 0.66, 95% CI 0.17-0.70, p <0.0001). The benefit
      of hormonal therapy was observed across all comorbidity strata and races. Effects
      were most evident in patients with poorly differentiated cancer (cancer specific
      mortality in favor of treatment HR 0.60, 95% CI 0.53-0.69, p <0.001). Benefit was
      not found in patients with well differentiated cancer (cancer specific mortality
      in favor of no treatment HR 1.92, 95% CI 0.90-4.10, p = 0.09). CONCLUSIONS:
      Hormonal therapy is associated with improved prostate cancer specific and overall
      survival in men with poorly differentiated cancer. Improved survival does not
      appear evident in men with well differentiated disease.

PMID- 17222629
TI  - Variation in the definition of biochemical recurrence in patients treated for
      localized prostate cancer: the American Urological Association Prostate
      Guidelines for Localized Prostate Cancer Update Panel report and recommendations
      for a standard in the reporting of surgical outcomes.
AB  - PURPOSE: The American Urological Association Prostate Guideline Update Panel was
      charged with updating the Guidelines for Clinically Localized Prostate Cancer. In
      assessing outcomes with treatment, it became apparent that a highly variable
      number of definitions exist with respect to biochemical recurrence. Herein, we
      review the variability in published definitions of biochemical recurrence and
      make recommendations directed toward improving this terminology by recommending a
      standard definition in patients treated with radical prostatectomy. MATERIALS AND
      METHODS: Four PubMed literature searches were performed between May 2001 and
      April, 2004 and covered articles published from 1991 through early 2004. The
      search terms included the MeSH major headings of prostate cancer and prostatic
      neoplasm. All potentially relevant articles were retrieved and a more detailed
      screen for relevance was performed. An article was considered relevant if it
      reported treatment outcomes of patients with clinical T1 or T2N0M0 prostate
      cancer. Data extractors recorded the definition of biochemical recurrence and
      definitions were then collapsed into categories representing the same criteria.
      The results of biochemical failure were subcategorized by initial treatment.
      RESULTS: Of 13,800 citations, a total of 436 articles were selected. Among these,
      a total of 145 articles contained 53 different definitions of biochemical
      recurrence for those treated with radical prostatectomy. Of these, the most
      common definition (35) was a prostate specific antigen of >0.2 ng/mL or a slight
      variation thereof. In addition, a total of 208 articles reported 99 different
      definitions of biochemical failure among those treated with radiation therapy. Of
      these, the American Society for Therapeutic Radiology and Oncology definition
      (70) and/or a variation thereof was the most commonly reported. In total, 166
      different definitions of biochemical failure were identified. Following radical
      prostatectomy, the Panel recommends defining biochemical recurrence as an initial
      serum prostate specific antigen of > or =0.2 ng/mL, with a second confirmatory
      level of prostate specific antigen of >0.2 ng/mL. The Panel recommends the use of
      the American Society for Therapeutic Radiology and Oncology criteria for patients
      treated with radiation therapy and acknowledges that these criteria will soon be
      updated although not yet published. CONCLUSIONS: A high degree of variability in
      the definition of biochemical recurrence exists following treatment for localized
      prostate cancer. Strict definitions for biochemical recurrence are necessary to
      identify men at risk for disease progression and to allow meaningful comparisons
      among patients treated similarly. The Panel acknowledges the American Society for
      Therapeutic Radiology and Oncology criteria and future modifications thereof for
      those receiving radiation therapy and recommends the newly developed American
      Urological Association criteria for those treated with radical prostatectomy. The
      purpose for the establishment of this standard is for data reporting purposes and
      for comparison of similarly treated patients. It is not intended to represent a
      threshold value for which to initiate treatment. The Panel acknowledges that the
      clinical decision to initiate treatment will be dependent on multiple factors
      including patient and physician interaction rather than a specific prostate
      specific antigen threshold value.

PMID- 17222630
TI  - Clinical and pathological features associated with the testicular tumor of the
      adrenogenital syndrome.
AB  - PURPOSE: Testicular tumor of the adrenogenital syndrome is a rare clinical entity
      found in young men with endocrine disorders. Histologically it resembles Leydig
      cell tumor. We 1) reviewed the clinical features of testicular tumor of the
      adrenogenital syndrome and 2) determined if special histopathological features of
      the tumor and synaptophysin reactivity could distinguish testicular tumor of the
      adrenogenital syndrome from Leydig cell tumor. MATERIALS AND METHODS: We reviewed
      the medical and pathological records for all patients with testicular tumor of
      the adrenogenital syndrome seen at our institution from 1978 to 2004. These
      tumors were examined by histological and immunophenotypic methods for comparison
      to Leydig cell tumor. RESULTS: A total of 14 males with an endocrine disorder had
      pathological evidence of testicular tumor of the adrenogenital syndrome. These
      tumors were often bilateral (93% or 13 of 14 cases), associated with pain (92% or
      12 of 13) and refractory to medical management with high dose exogenous steroids
      (93% or 13 of 14). Testicular tumor of the adrenogenital syndrome was managed by
      tumor enucleation in 7 patients (54%) and by radical orchiectomy in 6 (46%). All
      patients had resolution of pain at 3-month followup. Upon histological review
      features found to be more common to testicular tumor of the adrenogenital
      syndrome compared with Leydig cell tumor were nuclear pleiomorphism, low mitotic
      activity, extensive fibrosis, lymphoid aggregates, adipose metaplasia and
      prominent lipochrome pigment. Synaptophysin (ICN, Costa Mesa, California)
      reactivity was strong in testicular tumor of the adrenogenital syndrome but
      rarely observed in Leydig cell tumor. CONCLUSIONS: In our series medical
      treatment failed in patients with testicular tumor of the adrenogenital syndrome
      and conservative surgical therapy was possible in select individuals. We
      identified special histopathological and immunophenotypic features, including
      synaptophysin staining, which distinguish testicular tumor of the adrenogenital
      syndrome from Leydig cell tumor.

PMID- 17222632
TI  - The dual serotonin and noradrenaline reuptake inhibitor duloxetine for the
      treatment of interstitial cystitis: results of an observational study.
AB  - PURPOSE: We report an observational study to evaluate the efficacy and
      tolerability of duloxetine for interstitial cystitis. MATERIALS AND METHODS: A
      total of 48 women were prospectively treated for 2 months following an
      uptitration protocol to the target dose of 2 x 40 mg duloxetine per day. Patients
      received the target dose for 5 weeks. The efficacy of duloxetine treatment was
      assessed at week 8. The primary end point was a change in the overall well-being
      evaluated by a patient reported global response assessment. Secondary end points
      were changes in pain and urgency (visual analog scales), frequency and functional
      bladder capacity (48-hour voiding log), and changes in overall symptom severity
      (O'Leary-Sant index). RESULTS: There were 5 patients (10.4%) who were identified
      as responders and 17 patients (35.4%) who dropped out of the study exclusively
      due to side effects, with nausea present in all dropouts. No severe adverse
      events were reported. All 5 responders reported onset of symptom improvement but
      not until they had reached the target dose. Regarding secondary outcome
      parameters, duloxetine treatment did not result in statistically significant
      improvement of symptoms. Maximum urinary flow rate and residual volume were
      influenced more prominently in patients at the target dose, however, the changes
      did not appear to be clinically meaningful. CONCLUSIONS: Treatment of
      interstitial cystitis with duloxetine did not result in significant improvement
      of symptoms. The drug administration was safe but the tolerability of the drug
      was poor mainly due to nausea occurring with the starting dose of 20 mg per day.
      Based on the preliminary data of this observational trial we currently cannot
      recommend duloxetine as a therapeutic approach for interstitial cystitis.

PMID- 17222633
TI  - Changes in urine markers and symptoms after bladder distention for interstitial
      cystitis.
AB  - PURPOSE: We evaluated changes in urine markers and symptom scores after bladder
      distention in patients with interstitial cystitis. MATERIALS AND METHODS: Study
      subjects were 33 new patients who had undergone no prior interstitial cystitis
      treatment. Urine specimens were taken before and 1 month after bladder
      distention. University of Wisconsin symptom scores were done the same day as the
      urine specimen collection. Urine marker levels and symptom scores before and
      after distention were compared. Changes in markers were tested for associations
      with changes in symptom scores and other markers. Markers and specific symptoms
      before distention were tested for their association with post-distention symptom
      improvement. RESULTS: After distention the median total University of Wisconsin
      score decreased significantly (28.5 before, 20 after, p <0.001). A total of 12
      patients (36%) had at least 30% improvement in University of Wisconsin score, and
      8 patients (24%) had at least 50% improvement. No pre-distention markers or
      symptoms predicted which patients would have a good response. There were 2 urine
      markers that improved significantly after distention: anti-proliferative factor
      activity (median -96% before, -17% after, p <0.001) and heparin-binding epidermal
      growth factor-like growth factor levels (median 0.34 ng/mg creatinine before, 4.1
      after, p <0.001). None of the changes in urine markers associated with changes in
      symptom scores. CONCLUSIONS: The median symptom score for newly diagnosed
      patients with interstitial cystitis decreased after distention, but only a
      minority of patients had at least 30% symptom improvement. Bladder distention
      altered urine anti-proliferative factor activity and heparin-binding epidermal
      growth factor-like growth factor levels toward normal, but the mechanism of
      symptom relief after distention is still unknown.

PMID- 17222634
TI  - Hyperoxaluria in kidney stone formers treated with modern bariatric surgery.
AB  - PURPOSE: Nephrolithiasis and renal failure secondary to severe hyperoxaluria were
      complications of jejunoileal bypass for obesity, leading to the discontinuation
      of this procedure in the United States in 1980. Bariatric procedures currently in
      use have not been adequately evaluated for this complication. MATERIALS AND
      METHODS: We compared 24-hour urine chemistry studies of 132 patients with
      nephrolithiasis who had undergone bariatric surgery with the urine chemistry
      studies of patients who had undergone jejunoileal bypass, those with routine
      kidney stones and normal subjects. The primary aim was to determine if
      hyperoxaluria developed in patients who underwent bariatric surgery and had
      kidney stones as had been seen with jejunoileal bypass. RESULTS: Patients who
      have undergone modern bariatric surgery had an adjusted mean urine oxalate
      excretion of 83 mg per day compared to 39 mg per day for routine kidney stone
      formers and 34 mg per day for normal subjects (p <0.001 for both comparisons),
      but not quite as high as that found in patients treated with jejunoileal bypass
      (102 mg per day, p <0.001). Urine supersaturation of calcium oxalate, the main
      driving force for calcium oxalate stone formation, was higher in patients treated
      with bariatric surgery compared to routine kidney stone formers and normal
      subjects (p <0.001 for both comparisons). CONCLUSIONS: Hyperoxaluria is the most
      significant abnormality of urine chemistry studies in patients with kidney stones
      who have undergone bariatric surgery. Many of these patients have a degree of
      hyperoxaluria that could lead to kidney failure. Further studies are required to
      determine the prevalence of this problem in patients who have undergone bariatric
      surgery.

PMID- 17222635
TI  - Predicting urethral injury from pelvic fracture patterns in male patients with
      blunt trauma.
AB  - PURPOSE: Precise definition of pelvic fracture location may enable prediction of
      which subjects are at risk for urethral injury and understanding of the
      pathophysiological mechanism of injury. We determined the specific anterior
      pelvic injury locations associated with urethral injury. MATERIALS AND METHODS:
      We completed a retrospective, nested case-control study of 119 male patients
      evaluated at a single large level 1 trauma center between January 1, 1997 and
      July 15, 2003. We performed detailed measurements of the location, displacement
      and direction of force of each anterior pelvic fracture from computerized
      tomography and pelvic radiographs. Multiple logistic regression was used to
      determine associations between specific fracture locations and urethral injury
      after controlling for age, injury mechanism, injury severity and direction of
      force. RESULTS: Urethral injury was present in 25 patients and all had anterior
      pelvic fracture (inclusive of pubic symphysis diastasis). There were no urethral
      injuries in patients with fractures isolated to the acetabulum. Pelvic fractures
      that were independently associated with urethral injury from multiple regression
      analysis included displaced fractures of the inferomedial pubic bone, OR 6.4 (95%
      CI 1.6 to 24.9), and symphysis pubis diastasis, OR 11.8 (95% CI 4.0 to 34.5).
      Each millimeter of symphysis pubis diastasis or inferomedial pubic bone fracture
      displacement was associated with an approximately 10% increased risk of urethral
      injury. CONCLUSIONS: The location and displacement of anterior pelvic fractures
      in males predict risk of urethral injury and may be valuable in determining when
      evaluation of the urethra is appropriate.

PMID- 17222636
TI  - Post-percutaneous nephrolithotomy extensive hemorrhage: a study of risk factors.
AB  - PURPOSE: We identified risk factors predicting severe bleeding due to
      percutaneous nephrolithotomy. MATERIALS AND METHODS: Computerized data on 2,909
      patients who underwent a total of 3,878 percutaneous nephrolithotomy procedures
      between January 1995 and December 2005 were retrospectively reviewed. Data on
      patients who experienced severe bleeding requiring angiographic renal
      embolization were compared with those on other patients using univariate and
      multivariate analyses. We tested the characteristics of patients, kidneys and
      stones together with details of the operative procedure and surgeon experience.
      RESULTS: Severe bleeding complicated a total of 39 procedures (1%) in 25 males
      and 14 females with a mean age of 50.7 +/- 12.6 years. Associated morbidity
      included shock in 6 patients and perirenal hematoma in 4. Renal angiography
      revealed pseudoaneurysm in 20 patients, arteriovenous fistula in 9, the 2 lesions
      in 8 and arterial laceration in 2. Bleeding could be controlled with
      superselective embolization in 36 patients (92.3%). Followup was available on 33
      patients (mean 21 +/- 15 months). Renal function was stable in all patients
      except 3 who had a post-embolization increase in serum creatinine, of whom all
      had a solitary kidney and none required renal replacement therapy. Significant
      risk factors for severe bleeding were upper caliceal puncture, solitary kidney,
      staghorn stone, multiple punctures and inexperienced surgeon. CONCLUSIONS:
      Percutaneous nephrolithotomy should be performed by an experienced endourologist
      in patients at risk for severe bleeding, such as those with a solitary kidney or
      staghorn stones.

PMID- 17222637
TI  - Complications of 2,775 urological laparoscopic procedures: 1993 to 2005.
AB  - PURPOSE: We assessed the complications associated with urological laparoscopic
      surgery at a single high volume center during a 12-year period. MATERIALS AND
      METHODS: A retrospective chart analysis was performed, focusing on complications
      associated with 2,775 laparoscopic surgeries occurring between 1993 and 2005.
      These included radical nephrectomy (549), partial nephrectomy (345), donor
      nephrectomy (553), simple nephrectomy (186), pyeloplasty (301),
      nephroureterectomy (105), retroperitoneal lymph node dissection (86), renal
      ablation (81), adrenalectomy (106) and radical prostatectomy (463). Complication
      data were tabulated according to case number, procedure type, patient age, the
      American Society of Anesthesiologists score, conversion status, length of
      hospitalization, Clavien classification system and annual complication rate
      during the study. Statistical analysis was performed with Fisher's exact and chi
      square tests. RESULTS: A total of 614 complications (22.1%) occurred within each
      group, broken down into laparoscopic radical nephrectomy (20%), laparoscopic
      partial nephrectomy (28%), laparoscopic donor nephrectomy (28%), laparoscopic
      simple nephrectomy (15%), laparoscopic pyeloplasty (13.3%), laparoscopic
      nephroureterectomy (40.9%), laparoscopic retroperitoneal lymph node dissection
      (26.7%), laparoscopic renal tumor ablation (18.6%), laparoscopic adrenalectomy
      (25.4%) and laparoscopic radical prostatectomy (15%). Total intraoperative and
      postoperative complication rates were 4.7% and 17.5%, respectively. Vascular
      injuries were the most common intraoperative complications. Annual complication
      rates plateaued in the year 2000 and were not significantly different during the
      ensuing 4 years (p >0.05). Complications correlated with a greater American
      Society of Anesthesiologists score as well as a longer hospital stay (p <0.05).
      CONCLUSIONS: The data presented here help define the complication rates for
      laparoscopic urological procedures in experienced hands at a high volume
      institution.

PMID- 17222638
TI  - Staging rectourinary fistulas to guide surgical treatment.
AB  - PURPOSE: Surgical management for rectourinary fistulas remains a reconstructive
      challenge. There are few guidelines to direct the surgeon to the most successful
      and least morbid technique. We developed a rectourinary fistula staging system
      that allows selection of the most appropriate technique for the patient. We
      present the details of the staging system and surgical outcomes. MATERIALS AND
      METHODS: From July 1999 to July 2005 we treated 14 male patients with
      rectourinary fistula. Mean patient age was 68 years (range 62 to 73). Etiology
      was rectal injury during open radical prostatectomy in 5 patients, laparoscopic
      prostatectomy in 1, radiation induced fistula for prostate cancer treatment
      (brachytherapy and external beam radiation therapy) in 2, neoadjuvant external
      beam radiation therapy in 2, ischial decubitus ulcer in 3 with spinal cord
      injury, and cryotherapy and external beam radiation therapy in 1. Cases were
      staged as stage I--low (less than 4 cm from anal verge and nonirradiated), stage
      II--high (more than 4 cm from anal verge and nonirradiated), stage III--small
      (less than 2 cm irradiated fistula), stage IV--large (more than 2 cm irradiated
      fistula) and stage V--large (ischial decubitus fistula). Diverting colostomy was
      performed for stages III to V 6 weeks before definitive therapy. RESULTS:
      Patients were discharged home after 48 hours. A 22Fr urethral catheter maintained
      bladder drainage for 3 weeks until cystogram confirmed rectourinary fistula
      closure. Complications were superficial wound infection and postoperative
      reexploration of the gracilis flap due to bleeding in 1 case each. All patients
      were cured after a single operation. CONCLUSIONS: The surgical challenges of a
      variety of rectourinary fistula repairs can be managed with minimal morbidity and
      a high success rate using proper staging to guide urinary tract reconstruction.

PMID- 17222639
TI  - Complications of porcine small intestine submucosa graft for Peyronie's disease.
AB  - PURPOSE: We report outcomes and complications of the use of porcine small
      intestine submucosa for correcting penile curvature due to Peyronie's disease.
      MATERIALS AND METHODS: A retrospective study was performed in patients with
      severe penile curvature (greater than 60 degrees) requiring surgical correction
      for sexual function. Preoperatively all patients underwent evaluation, including
      history, physical and penile duplex ultrasound. Of these patients 19 underwent
      tunical grafting with 1-layer Surgisis small intestine submucosa. Postoperatively
      patients were evaluated with clinic visits and telephone interviews to assess
      results. RESULTS: A total of 19 patients 46 to 69 years old (mean age 54) were
      treated with tunical incision or excision and grafting with small intestine
      submucosa between March 2002 and July 2005. Average followup was 15 months (range
      3 to 43). Patients reported less penile pain with intercourse after surgery.
      There was no difference in Sexual Health Inventory for Men scores. Preoperatively
      12 men (63%) had erectile dysfunction, defined as Sexual Health Inventory for Men
      less than 21, while 10 (53%) reported postoperative erectile dysfunction. Seven
      of the 19 patients (37%) had recurrent penile curvature (greater than 10 degrees)
      and 5 (26%) had recurrent Peyronie's disease plaque. Our complication rate was
      37%, including hematoma at the graft site in 5 cases (26%), graft infection in 1
      (5%) and Peyronie's disease recurrence requiring plication in 1 (5%).
      CONCLUSIONS: Small intestine submucosa carries potential for grafting
      applications because it is easy to use and readily available. Our experience
      resulted in a 37% complication rate, which exceeds those previously reported with
      saphenous vein graft repair.

PMID- 17222640
TI  - Study of low bladder volume measurement using 3-dimensional ultrasound scanning
      device: improvement in measurement accuracy through training when bladder volume
      is 150 ml or less.
AB  - PURPOSE: Using a Bladder Scan BVI6100 portable 3-dimensional ultrasound scanning
      device we examined measured values of bladder volume, especially focusing on
      volumes of 150 ml or less. MATERIALS AND METHODS: A total of 89 men and 71 women
      were enrolled in the study. We performed a comparison study between the measured
      value (the average of 3 bladder volume measurements after a trial in male and
      female modes) using the BVI6100 and the actual measured value determined by
      urethral catheterization in each patient. We examined factors that could increase
      the error rate and measuring techniques to decrease measurement errors. We also
      reviewed the training effects of measurement for a year. RESULTS: Actual measured
      values in all patients correlated well with the average value of 3 measurements
      after a trial of BVI6100 in male mode. The correlation coefficient was 0.941
      (0.967 after a year), the mean +/- SD error rate was -2.0% +/- 22.0% (-2.0% +/-
      13.8% after a year) and the average variation coefficient was 12.4 (7.6 after a
      year). It was found that measurement results using the BVI6100 were influenced by
      patient factors, including extracted edges between the bladder wall and urine,
      thickened bladder wall, irregular bladder wall, flattened bladder, mistaking the
      prostate for the bladder in male mode, mistaking the bladder for the uterus in
      female mode, etc, and examiner factors, including changes in the angle between
      the BVI6100 and the abdominal wall, compatibility between the abdominal wall and
      the ultrasound probe, controlling deflection while using the probe, etc. It was
      also found that measurement accuracy could be improved regarding patient and
      examiner factors by choosing appropriate patients and performing concise
      measurement procedures (training effects). CONCLUSIONS: When appropriate patients
      are chosen and proper measurement is performed, the BVI6100 provides
      significantly higher accuracy for determining lower bladder volume compared with
      existing abdominal ultrasound methods.

PMID- 17222641
TI  - Urodynamic prolapse reduction alters urethral pressure but not filling or
      pressure flow parameters.
AB  - PURPOSE: To test the hypothesis that advanced stages of pelvic organ prolapse can
      result in a functional obstruction of the urethra, we studied the effects of
      manual prolapse reduction on urodynamic and urethral electromyographic parameters
      in women with stage III and IV pelvic organ prolapse. MATERIALS AND METHODS:
      Women with advanced pelvic organ prolapse undergoing clinical multichannel
      urodynamics with concentric needle electromyography of the urethra were invited
      to participate in this institutional review board approved study. Women underwent
      filling cystometry and electromyography with prolapse everted and with prolapse
      reduced. Women were randomized to cystometry order (reduced vs everted). All
      subjects underwent a third study with prolapse reduction. Maximum urethral
      closure pressure and quantitative electromyography of the striated urethral
      sphincter were determined at maximum cystometric capacity. During the pressure
      flow study voiding parameters, including urethral electromyography quieting, were
      determined. The nonparametric paired sign test was used to evaluate differences
      in urodynamic parameters and quantitative electromyography with pelvic organ
      prolapse reduced and unreduced. Results were considered significant at the 5%
      level. RESULTS: The 31 participants had mean age of 60 years (range 36 to 78) and
      83% were white. There were no clinically significant differences in maximum
      cystometric capacity, voided volume, maximal flow and detrusor pressure at
      maximal flow or time to maximal flow between the reduced and everted prolapse
      states. Prolapse reduction resulted in a clinically and statistically significant
      decrease in maximum urethral closure pressure (-31%) but it had no impact on
      quantitative urethral electromyography. CONCLUSIONS: These findings demonstrate
      that, although prolapse reduction significantly decreases maximum urethral
      closure pressure, it does not alter intrinsic neuromuscular activity of the
      striated urethral sphincter. Prolapse reduction does not alter any other filling
      or pressure flow parameter.

PMID- 17222642
TI  - Comparative analysis of urinary incontinence severity after autologous fascia
      pubovaginal sling, pubovaginal sling and tension-free vaginal tape.
AB  - PURPOSE: Autologous fascia, Pelvicol implant and polypropylene are common
      materials used in suburethral anti-incontinence procedures. We explored the
      relative effectiveness of the autologous fascia pubovaginal sling, Pelvicol
      pubovaginal sling and Gynecare TVT on self-reported postoperative urinary
      incontinence. MATERIALS AND METHODS: The study was a mailed cross-sectional
      survey of health related quality of life 1 to 3 years after suburethral anti
      incontinence surgery performed at our institution. The Incontinence Symptom Index
      was used to assess the presence and severity of urinary incontinence symptoms and
      the Incontinence Impact Questionnaire-7 was used to assess impairment. Regression
      models were developed to identify factors with an independent effect on the
      presence, severity and impairment of urinary incontinence symptoms. RESULTS: The
      questionnaire was returned by 69% of eligible respondents (173 of 250). Those
      with previous incontinence surgery (OR 11.0, 95% CI 2.3-51.4) and medical
      comorbidities (OR 1.6, 95% CI 1.1-2.2) were more likely to report urinary
      incontinence symptoms, ie incontinence symptom index greater than 0. Symptom
      severity, which was analyzed only in respondents with urinary incontinence
      symptoms, was greater in the Pelvicol than in the autologous fascia pubovaginal
      sling and TVT groups (each p <0.01). No significant difference was observed
      between the TVT and autologous fascia pubovaginal sling groups (p = 0.15). Also
      associated with higher urinary incontinence symptom severity scores were body
      mass index (p = 0.03), a history of incontinence surgery (p = 0.01) and lower
      education (p <0.01). Impairment from urinary incontinence, as assessed by the
      Incontinence Impact Questionnaire-7, was associated with body mass index, severe
      depression and current smoking (each p = 0.01) but not with surgical treatment
      group. CONCLUSIONS: Women who received an autologous fascia pubovaginal sling or
      TVT reported lower symptom severity scores than those who had a Pelvicol
      pubovaginal sling. Impairment was not associated with procedure type. These
      findings suggest better outcomes with autologous fascia pubovaginal sling and
      TVT. Randomized, controlled trials are needed to confirm these findings.

PMID- 17222644
TI  - A preliminary study of JM-27: a serum marker that can specifically identify men
      with symptomatic benign prostatic hyperplasia.
AB  - PURPOSE: Benign prostatic hyperplasia is a common disease in men that until
      recently was considered a single disease with varying symptoms. Our recent
      analysis has revealed that a molecular marker, JM-27, is able to distinguish at
      the tissue level between highly symptomatic individuals and those with
      histological disease. The goal of these studies was to determine if a serum based
      assay to detect JM-27 could distinguish men with different forms of benign
      prostatic hyperplasia. MATERIALS AND METHODS: A serum based enzyme-linked
      immunosorbent assay was developed using a novel anti-JM-27 monoclonal antibody.
      The assay was sensitive, detecting JM-27 at the low ng/ml level within the serum.
      A quantitative measurement of serum JM-27 levels was performed in 68 patients.
      The patients consisted of 3 groups of 29 patients with asymptomatic benign
      prostatic hyperplasia (American Urological Association symptom score of 15 or
      less), 39 with symptomatic benign prostatic hyperplasia (American Urological
      Association symptom score 16 to 32) and 17 with confirmed prostate cancer. The
      assay cutoff was determined after a pilot run of samples and applied
      prospectively. RESULTS: Using the determined cutoff, serum levels of JM-27 can
      distinguish between symptomatic and asymptomatic patient sets. The sensitivity
      and specificity of the assay are 90% and 77%, respectively. The presence of
      prostate cancer in these men does not appear to alter the marker levels.
      CONCLUSIONS: The present study is believed to represent the first
      characterization of a serum based marker for severe benign prostatic hyperplasia.

PMID- 17222646
TI  - Open versus laparoscopic radical prostatectomy: a prospective comparison of
      postoperative urinary incontinence rates.
AB  - PURPOSE: We compared the 12-month postoperative urinary incontinence rates of
      open radical retropubic and laparoscopic radical prostatectomy. MATERIALS AND
      METHODS: This prospective study included all men with clinically localized
      prostate cancer scheduled for radical prostatectomy (open retropubic or
      laparoscopic) at the University of Alberta between October 1999 and July 2002.
      Preoperative evaluation included a 24-hour pad test, fluid volume voiding diary
      and International Prostate Symptom Score questionnaire. Postoperative evaluation
      included a 24-hour pad test at 3 and 12 months, as well as a voiding diary and
      International Prostate Symptom Score questionnaire at 3, 6, 9 and 12 months.
      RESULTS: A total of 239 patients met the eligibility criteria and consented to
      participate (172 open radical retropubic prostatectomy, 67 laparoscopic radical
      prostatectomy). Of the patients 87% (148) treated with open radical retropubic
      prostatectomy and 88% (57) of those treated with laparoscopic radical
      prostatectomy completed 12-month followup (p = 0.50). According to 24-hour pad
      testing 13% of those treated with open radical retropubic prostatectomy and 17%
      of those treated with laparoscopic radical prostatectomy remained incontinent at
      1 year (p = 0.26). There was no difference in 24-hour pad weight, urinary symptom
      score and urinary quality of life at 1 year between the open and laparoscopic
      groups overall, or when stratified according to 12-month continence status. The
      majority of subjects in both groups described mild symptoms and a general
      satisfaction with urinary quality of life. CONCLUSIONS: Based on objective and
      subjective measures, there were no differences in urinary functional outcomes 1
      year after open radical retropubic prostatectomy or laparoscopic radical
      prostatectomy. Urinary incontinence was found to affect a similar proportion of
      patients who underwent open (13%) and laparoscopic (17%) radical prostatectomy 12
      months postoperatively.

PMID- 17222647
TI  - Limitations of laparoscopy for bilateral nephrectomy for autosomal dominant
      polycystic kidney disease.
AB  - PURPOSE: We retrospectively studied outcomes following bilateral hand assisted
      laparoscopic nephrectomy. MATERIALS AND METHODS: We retrospectively reviewed the
      charts of 18 patients with symptomatic autosomal dominant polycystic kidney
      disease who underwent bilateral hand assisted laparoscopic nephrectomy.
      Preoperative radiographic imaging was reviewed retrospectively to determine
      kidney size based on an ellipsoid shape. A visual analog pain scale with scores
      of 0 to 10 to assess pain related to autosomal dominant polycystic kidney disease
      was measured preoperatively and postoperatively. RESULTS: Average patient age was
      48.2 years (range 30 to 64). Of the patients 14 successfully underwent bilateral
      hand assisted laparoscopic nephrectomy, while 4 required open conversion. A total
      of 16 patients underwent nephrectomy for pain and 2 underwent surgery for
      frequent recurrent symptomatic urinary tract infections. All patients except 1
      underwent renal transplantation before bilateral nephrectomy. There was a
      significant difference in the volume of the right and left kidneys between the
      hand assisted laparoscopic and open groups (mean +/- SD 1,043 +/- 672 and 1,058
      +/- 603.8 vs 4,052 +/- 548 and 3,592 +/- 1,752 cm(3), p <0.001 and 0.06
      respectively). There were 5 complications, including wound infection and
      protracted ileus in 2 patients each, and incisional hernia in 1. In addition, the
      difference in mean preoperative and postoperative visual analog pain scores was
      statistically significant (6.9, range 3 to 10 and 0.5, range 0 to 2, p <0.05).
      CONCLUSIONS: Bilateral laparoscopic hand assisted nephrectomy is a safe and
      reliable option in patients requiring removal of the 2 kidneys in a single
      setting. Rather than performing staged nephrectomies, hand assisted laparoscopic
      nephrectomy allows the single administration of general anesthesia and provides
      effective relief of bothersome symptoms in patients with symptomatic autosomal
      dominant polycystic kidney disease. This procedure is safe in patients with renal
      transplants. Patients with massive polycystic kidneys with a kidney volume of
      greater than 3,500 cc are at increased risk for open conversion and they may have
      improved outcomes if open nephrectomy is attempted from the outset.

PMID- 17222648
TI  - Long-term comparative outcomes between 2 common ureteroneocystostomy techniques
      for renal transplantation.
AB  - PURPOSE: We compared the incidence of ureteral complications between the classic
      (Lich-Gregoir) technique and the recently popularized single stitch (Shanfield)
      technique in renal transplantation. MATERIALS AND METHODS: The charts of 721
      consecutive transplant recipients from May 1999 to July 2002 were retrospectively
      reviewed. Ureteral and nonureteral complications were reviewed at 3 to 5-year
      followup. RESULTS: Of the 721 recipients evaluated 713 were included in the
      study. There were 360 recipients in the Lich-Gregoir group and 353 in the
      Shanfield group. A significantly higher rate of ureteral complications occurred
      in the Shanfield group compared to the Lich-Gregoir group (15.6% vs 3.9%, p
      <0.0001). The Shanfield group consisted of 20 patients with ureteral leakage, 21
      with hematuria, 11 with strictures and 3 who had ureteral stones. The Lich
      Gregoir group had 8 patients with ureteral leakage, 5 with hematuria and 1 with a
      stricture. In comparison, urinary tract infections, delayed graft function and
      rejection rates were not significantly different between the 2 groups (p = 0.76,
      0.12 and 0.19, respectively). CONCLUSIONS: In contrast to other reports, the
      Shanfield group had significantly more ureteral complications. In particular the
      Shanfield technique may predispose patients to higher rates of hematuria and
      stone formation. Based on this large series and published meta-analyses we
      believe that the stented Lich-Gregoir anastomosis is the superior
      ureteroneocystostomy technique in renal transplantation.

PMID- 17222649
TI  - High dose zinc increases hospital admissions due to genitourinary complications.
AB  - PURPOSE: Zinc is a common dietary supplement that is widely believed to have
      beneficial health effects. To assess the impact of high dose supplemental zinc on
      genitourinary diseases we analyzed a recent randomized trial comparing zinc,
      antioxidants and their combination to placebo for complications related to the
      genitourinary tract. MATERIALS AND METHODS: In a further analysis of the recent
      Age-related Eye Disease Study we examined the data pool for primary International
      Classification of Diseases, 9th revision codes given for hospital admissions
      related to urological problems. The Age-Related Eye Disease Study randomized
      3,640 patients with age related macular degeneration to 1 of 4 study arms,
      including placebo, antioxidants (500 mg vitamin C, 400 IU vitamin E and 15 mg
      beta-carotene), 80 mg zinc and antioxidant plus zinc. Statistical analyses using
      Fisher's exact test were performed. RESULTS: We found a significant increase in
      hospital admissions due to genitourinary causes in patients on zinc vs nonzinc
      formulations (11.1% vs 7.6%, p = 0.0003). The risk was greatest in male patients
      (RR 1.26, 95% CI 1.07-1.50, p = 0.008). In the study group of 343 patients
      requiring hospital admission the most common primary International Classification
      of Diseases, 9th revision codes included benign prostatic hyperplasia/urinary
      retention (benign prostatic hyperplasia), urinary tract infection, urinary
      lithiasis and renal failure. When comparing zinc to placebo, significant
      increases in urinary tract infections were found (p = 0.004), especially in
      females (2.3% vs 0.4%, RR 5.77, 95% CI 1.30-25.66, p = 0.013). Admissions for
      urinary lithiasis approached significance in men on zinc compared to placebo
      (2.0% vs 0.5%, RR = 4.08, 95% CI 0.87-19.10). There was no increase in prostate
      or other cancers with zinc supplementation. A significant decrease in prostate
      cancer diagnoses was seen in patients receiving antioxidants vs placebo (RR =
      0.6, 95% CI 0.49-0.86, p = 0.049). Subgroup analysis revealed that this finding
      was significant in men who smoked but not in nonsmokers. CONCLUSIONS: Zinc
      supplementation at high levels results in increased hospitalizations for urinary
      complications compared to placebo. These data support the hypothesis that high
      dose zinc supplementation has a negative effect on select aspects of urinary
      physiology.

PMID- 17222650
TI  - The role of computerized tomographic urography in the initial evaluation of
      hematuria.
AB  - PURPOSE: We determined the usefulness of computerized tomographic urography for
      the initial evaluation of patients with hematuria as an alternative to excretory
      urography. MATERIALS AND METHODS: A total of 259 patients (140 men and 119
      women), age range 20 to 100 (mean 59.4) years, underwent computerized tomographic
      urography for the evaluation of hematuria and were available for followup. A
      cohort of 253 patients (153 men, 100 women), age range 21 to 92 (mean 57.6)
      years, underwent conventional excretory urography and were evaluated for
      comparison. RESULTS: A source of hematuria was identified in 107 patients (41.3%)
      in the computerized tomographic urography cohort and in 103 patients (40.7%) in
      the excretory urography cohort. Computerized tomographic urography alone
      identified a source of hematuria in 25.5% of these patients with the most
      commonly diagnosed lesions being renal calculi (18.9%), ureteral calculi (2.7%)
      and renal pelvic masses (2.3%) in the upper tract (0.94 sensitivity), and bladder
      masses (8.1%), prostatic abnormalities (5.4%) and inflammatory disorders (3.5%)
      in the lower tract (0.40 sensitivity, 0.99 specificity). The overall detection
      rate (19.5%), most commonly diagnosed lesions, and lower urinary tract
      sensitivity and specificity were similar in the excretory urography cohort.
      However, excretory urography exhibited a markedly lower sensitivity in detecting
      upper tract lesions (0.50). CONCLUSIONS: Computerized tomographic urography
      exhibited a significantly higher sensitivity than conventional excretory
      urography in detecting upper tract pathology (94.1% vs 50%). However, sensitivity
      for detecting lower tract lesions was low (40% or less), suggesting that
      computerized tomographic urography offers a comprehensive alternative to
      excretory urography but does not obviate the need for adjunctive
      cystourethroscopy for accurate evaluation of the lower urinary tract.

PMID- 17222651
TI  - Is the metabolic syndrome an independent risk factor for erectile dysfunction?
AB  - PURPOSE: We determined the role of the metabolic syndrome as an independent risk
      factor for erectile dysfunction. MATERIALS AND METHODS: Men participating in a
      health screening project completed the International Index of Erectile Function
      5. The metabolic syndrome was defined according to the 2005 International
      Diabetes Federation consensus definition. Multiple linear regression, ANOVA and
      chi-square tests were used to investigate the impact of the metabolic syndrome on
      erectile dysfunction. RESULTS: A total of 2,371 men with a mean age of 46.1 years
      (SD 9.9, range 30 to 69) were analyzed. Of the men 33.4% (652) had no erectile
      dysfunction (International Index of Erectile Function-5 score 22 to 25), 59.7%
      (1,166) had mild erectile dysfunction (International Index of Erectile Function-5
      score 17 to 21) and 6.9% (134) had moderate to severe erectile dysfunction
      (International Index of Erectile Function-5 score 5 to 16). The metabolic
      syndrome was present in 33.8% (794). In a multiple linear regression analysis an
      increased waist-to-hip ratio (p = 0.01) and metabolic syndrome (p = 0.01) turned
      out to be independently associated with a decreased International Index of
      Erectile Function-5 score. When stratified according to age, the metabolic
      syndrome was correlated to erectile dysfunction only in men 50 years old or older
      with an increase of severe erectile dysfunction by 48% (p = 0.01). CONCLUSIONS:
      The metabolic syndrome and an increased waist-to-hip ratio are independently
      associated with a decreased International Index of Erectile Function-5 score. The
      metabolic syndrome in men older than 50 years is significantly associated with a
      higher proportion of moderate to severe erectile dysfunction.

PMID- 17222652
TI  - Circulating monocyte oxidative activity is increased in patients with type 2
      diabetes and erectile dysfunction.
AB  - PURPOSE: We investigated the relationship between oxidative stress and diabetic
      erectile dysfunction. MATERIALS AND METHODS: A total of 23 patients with a mean
      +/- SD age of 56.7 +/- 5.6 years, a history of type 2 diabetes for 10.0 +/- 8.3
      years and erectile dysfunction, as tested by the International Index of Erectile
      Function questionnaire, but without vascular and neurological complications, and
      15 age matched patients with diabetes without erectile dysfunction were
      recruited. Circulating monocyte oxidative activity by cytofluorometry, and
      endothelin-1, intercellular adhesion molecule-1, plasminogen activator inhibitor
      1 by enzyme linked immunosorbent assay were evaluated in all patients in the
      study. RESULTS: Monocyte free radical production, and total and low density
      lipoprotein cholesterol were higher in patients with than in those without
      erectile dysfunction (p <0.03, <0.02 and <0.05, respectively). In all patients
      the International Index of Erectile Function score inversely correlated with low
      density lipoprotein (p <0.05), while in patients with erectile dysfunction it
      negatively correlated with age (p <0.03), body mass index (p <0.02), endothelin-1
      (p <0.02) and intercellular adhesion molecule-1 (p <0.05). Endothelin-1,
      intercellular adhesion molecule-1 and plasminogen activator inhibitor-1 were not
      different in patients with diabetes with and without erectile dysfunction.
      CONCLUSIONS: In men with type 2 diabetes who have erectile dysfunction but are
      asymptomatic for cardiovascular disease oxidative activation of monocytes is
      increased and it is related to other risk factors of endothelial dysfunction.

PMID- 17222653
TI  - Application of 2 vibrators salvages ejaculatory failures to 1 vibrator during
      penile vibratory stimulation in men with spinal cord injuries.
AB  - PURPOSE: Penile vibratory stimulation is the treatment of first choice for
      anejaculation in men with spinal cord injury. Nonresponders to penile vibratory
      stimulation are usually referred for electroejaculation or surgical sperm
      retrieval. Compared to penile vibratory stimulation these methods are invasive
      and usually yield lower total motile sperm, potentially limiting options for
      assisted reproductive technologies. To avoid these less than ideal options a
      simple method to salvage penile vibratory stimulation failures would be of
      benefit to spinal cord injured patients. We investigated the recovery rate when 2
      vibrators were used to salvage ejaculatory failures to 1 vibrator in men with
      spinal cord injury. MATERIALS AND METHODS: A retrospective chart review was
      performed in 297 spinal cord injured men who underwent a total of 965 trials of
      penile vibratory stimulation at our center between 1991 and 2006. Only trials
      with high amplitude vibrators were examined. All men underwent 2 or more penile
      vibratory stimulation trials using 1 vibrator applied to the dorsum or frenulum
      of the glans penis. Men failing to ejaculate with 1 vibrator received 1 or more
      trials in which the glans penis was then sandwiched between 2 vibrators. RESULTS:
      Of all men 49% and 57% of those whose level of injury was T10 or above responded
      to penile vibratory stimulation with 1 vibrator. Of failures with 1 vibrator 22%
      responded to penile vibratory stimulation with 2 vibrators. CONCLUSIONS:
      Application of 2 vibrators salvaged ejaculatory failures to 1 vibrator during
      penile vibratory stimulation procedures in men with spinal cord injury. This
      simple penile vibratory stimulation sandwich method is recommended before
      referring patients for electroejaculation or surgical sperm retrieval.

PMID- 17222654
TI  - Bilateral cavernous nerve interposition grafting during radical retropubic
      prostatectomy: Memorial Sloan-Kettering Cancer Center experience.
AB  - PURPOSE: Cavernous nerve graft is an option for men requiring bilateral cavernous
      nerve resection for cancer control during radical prostatectomy. We determined
      the success rate and identified determinants of success of bilateral cavernous
      nerve grafting following resection of the 2 nerves during radical prostatectomy
      in patients who were potent preoperatively. MATERIALS AND METHODS: We
      retrospectively reviewed the records of 44 consecutive patients who underwent
      bilateral nerve grafting from 1999 to 2004. Postoperative erectile function was
      defined as the achievement of erections satisfactory for intercourse with or
      without oral medication. We calculated cumulative erectile function recovery
      rates using Kaplan-Meier curves. The log rank test was used to compare variables
      affecting erectile function recovery with p <0.0083 considered significant after
      adjusting for the number of variables evaluated using the Bonferroni correction.
      RESULTS: The overall 5-year cumulative recovery of erectile function permitting
      penetration was 34% and the rate of consistent penetration was 11%. None of the
      analyzed variables were significantly associated with recovery of postoperative
      erectile function, including patient age (p = 0.3), incomplete bilateral
      cavernous nerve resection (p = 0.045), sural nerve grafts compared to
      genitofemoral or ilioinguinal nerves as donor sites (p = 0.067), post-radiation
      salvage radical prostatectomy (p = 0.15), neoadjuvant hormone therapy (p = 0.7)
      and comorbidities (p = 0.15) or medications (p = 0.4) affecting EF. CONCLUSIONS:
      Bilateral cavernous nerve grafts might be beneficial in select patients. A
      definitive answer awaits the performance of a multi-institutional, randomized,
      controlled trial.

PMID- 17222655
TI  - Bidirectional relationship between depression and erectile dysfunction.
AB  - PURPOSE: We specified the interrelationship between depressive mood and erectile
      dysfunction. MATERIALS AND METHODS: The target population consisted of men who
      were 50, 60 or 70 years old and residing in the study area in Finland in 1994.
      Questionnaires were mailed to 3,143 men in 1994 and to 2,837 men 5 years later.
      The followup sample consisted of 1,683 men who responded to the baseline and
      followup questionnaires. RESULTS: Erectile dysfunction was strongly associated
      with untreated and treated depressive symptoms. The prevalence OR adjusted for
      potential confounders was 2.6 (95% CI 1.8-3.8) for untreated and 3.3 (95% CI 1.6
      7.1) for treated depressive symptoms at the beginning of followup. The incidence
      of erectile dysfunction was 59/1,000 person-years (95% CI 39-90) in men with
      depressive mood and 37/1,000 person-years (95% CI 32-43) in those free of the
      disorder. Compared with men free of depressive symptoms who did not use
      medication for psychological disorders at study entry the adjusted incidence
      density ratio of erectile dysfunction was 4.5 (95% CI 2.2-9.2) in men with
      treated depressive symptoms and 1.2 (0.7-2.1) in those with untreated depressive
      symptoms. The incidence of depressive mood was 20/1,000 person-years in men with
      erectile dysfunction and 11/1,000 person-years in those free of erectile
      dysfunction. The adjusted incidence density ratio of depressive mood was 1.9 (95%
      CI 1.1-3.3) in men with erectile dysfunction compared with those free of it at
      entry. CONCLUSIONS: Moderate or severe depressive mood or antidepressant
      medication use may cause erectile dysfunction and erectile dysfunction
      independently may cause or exacerbate depressive mood.

PMID- 17222656
TI  - Care seeking and treatment for urinary incontinence in a diverse population.
AB  - PURPOSE: We examined care seeking and treatment for urine leakage in the Boston
      Area Community Health Survey, a racially and ethnically diverse, community based
      study of urological and gynecological symptoms and their correlates. MATERIALS
      AND METHODS: Boston Area Community Health Survey used a multistage, stratified
      cluster design to enroll 5,506 black, Hispanic and white adults. Subjects were 30
      to 79 years old and residents of Boston, Massachusetts. Data were obtained during
      a 2-hour in home interview. Analyses for this report include the 331 women and
      128 men who reported weekly incontinence, defined as urine leakage that occurred
      1 or more times weekly in the last year. RESULTS: Of women 45% and 22% of men
      with weekly incontinence reported ever having sought care for it. Of those who
      sought care 60% reported receiving treatment and half of those who were treated
      continued to have daily leakage. Of treated women 50% and 40% of treated men
      reported moderate to great frustration with continued urine leakage. CONCLUSIONS:
      This study demonstrates that the majority of men and women who experience weekly
      urinary incontinence do not seek care for it, many who sought treatment believe
      that none was provided and many who received treatment continue to have troubling
      symptoms. The public should be educated to seek care for urine leakage, health
      care providers should take the initiative to ask their patients about urinary
      symptoms and more attention should be given to ensuring that, when treatment is
      given, it is appropriate and effective.

PMID- 17222657
TI  - Adult anterior urethral strictures: a national practice patterns survey of board
      certified urologists in the United States.
AB  - PURPOSE: We determined the methods and patterns of the evaluation of and
      treatment for adult anterior urethral stricture disease by practicing urologists
      in the United States. MATERIALS AND METHODS: A nationwide survey of practicing
      members of the American Urological Association was performed by a mailed
      questionnaire. A total of 1,262 urologists were randomly selected from all 50
      states, of whom 431 (34%) completed the questionnaire. RESULTS: Most urologists
      (63%) treat 6 to 20 urethral strictures yearly. The most common procedures used
      by those surveyed for urethral strictures were dilation (92.8%), optical internal
      urethrotomy (85.6%) and endourethral stent (23.4%). Minimally invasive procedures
      are used more frequently that any open urethroplasty technique. Furthermore, most
      urologists (57.8%) do not perform urethroplasty surgery. When used, the most
      common urethroplasty surgeries performed were end-to-end anastomotic
      urethroplasty, perineal urethrostomy and ventral skin graft urethroplasty. Few
      urologists (4.2%) performed buccal mucosa grafts. For a long bulbar urethral
      stricture or short bulbar urethral stricture refractory to internal urethrotomy
      20% to 29% of respondents would refer to another urologist, while 31% to 33%
      would continue to manage the stricture by minimally invasive means despite
      predictable failure. Of the urologists 74% believed that the literature supports
      a reconstructive surgical ladder, in which urethroplasty is only performed after
      repeat failure of endoscopic methods. CONCLUSIONS: Most urologists in the United
      States have little experience with urethroplasty surgery. Most urologists
      erroneously believe that the literature supports a reconstructive surgical ladder
      for urethral stricture management. Unfamiliarity with the literature and
      inexperience with urethroplasty surgery have made the use of endoscopic methods
      inappropriately common.

PMID- 17222658
TI  - Highlights from the combined Society of Urodynamics and Female Urology, and
      International Society of Pelvic Neuromodulation annual meeting.

PMID- 17222659
TI  - Tubularized incised plate for mid shaft and proximal hypospadias repair.
AB  - PURPOSE: We report outcomes from tubularized incised plate repair of mid shaft
      and proximal hypospadias by a single surgeon. MATERIALS AND METHODS: Chart review
      of all patients undergoing mid shaft and proximal hypospadias was performed.
      Those with tubularized incised plate were divided into 2 groups for mid shaft and
      proximal repairs. Group 1 underwent single layer urethroplasty using chromic
      catgut suture, while group 2 underwent 2-layer polyglactin subepithelial closure.
      All patients had a dartos barrier flap, while spongioplasty was also done in
      group 2 when possible. RESULTS: A total of 30 patients underwent mid shaft
      repairs, while 35 had more proximal defects. Complication rates for mid shaft
      repairs did not differ between the 2 groups, and averaged 13%. However,
      complications in mid shaft vs proximal repairs (37%) were significantly different
      (p = 0.04). Overall complications (53% vs 25%) and incidence of fistulas (33% vs
      10%) decreased in proximal repairs from group 1 to 2. CONCLUSIONS: Tubularized
      incised plate repair was applicable for all mid shaft hypospadias cases and for
      those more proximal cases when ventral curvature could be straightened without
      plate transection and the incised plate was grossly supple. Outcomes were
      improved using 2-layer subepithelial tubularization of the neourethra. Results of
      mid shaft vs proximal hypospadias repairs are significantly different and should
      be reported separately.

PMID- 17222660
TI  - Cost-utility analysis of treatment algorithms for moderate grade vesicoureteral
      reflux using Markov models.
AB  - PURPOSE: The optimal treatment algorithm for vesicoureteral reflux remains
      controversial. Previous decision analyses have attempted to determine the best
      approach solely from the cost or cure perspective but have not combined the goals
      of minimizing treatment and disease burden. We incorporated these considerations
      into a contemporary, comprehensive analysis of treatment for vesicoureteral
      reflux. MATERIALS AND METHODS: We examined costs from the perspective of the
      medical institution, and utility from the perspective of parents of children with
      grades II and III vesicoureteral reflux. Cost-utility analysis using Markov
      modeling was performed to ascertain which of 5 treatment algorithms best
      minimized morbidity and cost. A higher utility value was based on minimizing
      treatment and disease burden. Measures of treatment and disease burden included
      duration of suppressive antibiotics, number of invasive studies, pyelonephritis
      episodes, endoscopic treatments and open operations. All variables were varied
      spanning realistic ranges during sensitivity analyses to determine threshold
      values. RESULTS: The protocol of no antibiotics or followup imaging yielded the
      best cost-utility for vesicoureteral reflux grades II and III. Sensitivity
      analysis of variables spanning realistic ranges demonstrated that utility
      penalties for invasive imaging and outpatient pyelonephritis were particularly
      important in determining the highest utility protocols, with threshold values
      ranging from -0.5 to -0.8. CONCLUSIONS: In our models of treatment for
      vesicoureteral reflux a noninterventional approach constitutes the highest
      utility and least costly treatment for moderate grade reflux. Given the relative
      dearth of randomized trials, these analyses provide guidelines for current
      management of vesicoureteral reflux.

PMID- 17222662
TI  - A review of failures of endoscopic treatment of vesicoureteral reflux with
      dextranomer microspheres.
AB  - PURPOSE: We evaluated the appearance of the mound of failed endoscopic
      dextranomer microsphere injections at the time of reinjection or open ureteral
      reimplantation. MATERIALS AND METHODS: We performed a multi-institutional study
      of 80 patients (97 ureters) who were diagnosed with vesicoureteral reflux and had
      failed endoscopic treatment with dextranomer microspheres. Observations of
      injected mound characteristics were made during the time of reinjection or at
      open ureteral reimplantation. Correlations were made with the pre-injection grade
      of reflux, volume of initial injection, number of punctures used for the initial
      injection and presence of symptoms of dysfunctional voiding. RESULTS: Examination
      of the failed injection sites before subsequent injections or open surgery
      revealed mound abnormalities in all but 13 of the 97 ureters. Of the cases 49%
      demonstrated a shifted mound, 22% an absent mound and 10% a loss of volume in the
      mound. Of the 13 patients with normal appearing mounds 7 had improved reflux
      grade, 3 had worsened grade and 3 had no change. Patients with dysfunctional
      voiding symptoms had a second injection failure rate of 44%, compared to a 13%
      rate in those without symptoms of voiding dysfunction. CONCLUSIONS: Most failures
      of endoscopic correction are associated with mound shifting. The presence of a
      perfect mound does not predict success. Dysfunctional voiding predicts a lower
      success rate after a second injection.

PMID- 17222665
TI  - Pediatric urinary incontinence: evaluation of bladder wall wraparound sling
      procedure.
AB  - PURPOSE: In 1996 a surgical procedure for sphincter deficiency was reported in
      patients with neurogenic urinary incontinence. To our knowledge we report the
      first series that assesses this procedure since it was initially described.
      MATERIALS AND METHODS: Seven female and 7 male patients with spinal dysraphism
      and neurogenic intrinsic sphincter deficiency underwent surgery between 1997 and
      2005. All patients had an associated poorly compliant or small capacity bladder.
      Patient age ranged from 8 to 22 years (mean 14) and all patients presented with
      persistent urinary incontinence despite intermittent catheterization and
      pharmacotherapy. Evaluation was based on clinical examination, as well as
      preoperative and postoperative urodynamic assessments. The surgical procedure
      involved wrapping a pedicle strip of anterior bladder wall around the bladder
      neck and fixing it on the pubic symphysis. Bladder augmentation cystoplasty was
      also routinely performed during the same procedure. RESULTS: Of 14 patients 13
      were completely dry and 1 had stress incontinence. Followup was 2 to 8 years
      (mean 5). Postoperative urodynamic evaluation showed a maximum urethral pressure
      increase of 40%. We also observed an increase in bladder capacity of 105% and
      improved bladder compliance (7 ml/cm H(2)O preoperatively vs 35 ml/cm H(2)O
      postoperatively). CONCLUSIONS: The bladder wall wraparound sling procedure
      provides excellent results for continence in association with bladder
      augmentation.

PMID- 17222666
TI  - Usefulness of short-term retrievable ureteral stent in pediatric laparoscopic
      pyeloplasty.
AB  - PURPOSE: Methods of stenting after laparoscopic pyeloplasty have included
      indwelling Double-J stents and percutaneous nephrostomy tubes. The disadvantages
      of these methods are that they necessitate a second surgery for stent removal or
      require an external drainage bag. To circumvent these issues, the tolerance,
      safety and outcomes of using a Double-J ureteral stent with a dangler, permitting
      early office removal, was investigated in a series of pediatric laparoscopic
      pyeloplasties. MATERIALS AND METHODS: Medical records from a consecutive series
      of pediatric patients undergoing transperitoneal laparoscopic pyeloplasties were
      reviewed. Indications for surgery included ipsilateral flank pain with severe
      hydronephrosis (12 patients), recurrent pyelonephritis with severe hydronephrosis
      (2), and hematuria and flank pain (6). All patients were discharged home within
      24 to 48 hours of the procedure with prophylactic oral antibiotics. The stent was
      removed by postoperative day 18 during a followup office visit. Patient tolerance
      of the indwelling stent, outpatient removal and success of pyeloplasty were
      assessed. RESULTS: A total of 20 patients underwent transperitoneal laparoscopic
      pyeloplasty by 1 surgeon (LAB) between 2001 and 2005. All patients underwent
      cystoscopy and retrograde Double-J ureteral stent placement before pyeloplasty
      under the same anesthesia. Mean patient age at operation was 11.3 years (median
      11.3, range 4.6 to 17.2). Stents were left indwelling for a mean of 10.3 days
      (median 10, range 7 to 18). All patients tolerated the Double-J stent well, with
      2 requiring anticholinergic therapy for mild urgency symptoms and 1 demonstrating
      urinary tract infection. All patients tolerated outpatient stent removal via the
      dangler at the office without discomfort. One patient was lost to followup. At a
      mean followup of 1.04 years (range 0.1 to 2.88) 17 of 19 patients (89%) had
      resolution of flank pain/urinary tract infections, with sonographic improvement
      in hydronephrosis with or without endoscopic intervention. Six patients (30%) had
      flank pain with or without continuous hydronephrosis and required re-stenting,
      and 3 also required balloon dilation. Of these 6 patients 2 (10%) had recurrent
      ureteropelvic junction obstruction and required open pyeloplasty. All patients
      are now clinically and radiologically unobstructed and asymptomatic. CONCLUSIONS:
      Pediatric transperitoneal laparoscopic pyeloplasty with indwelling Double-J
      ureteral stent with a dangler is successful and the stent is well tolerated.
      Whether the duration of ureteral stenting affects the surgical success will
      require further controlled long-term studies.

PMID- 17222668
TI  - The long-term followup of 33 cases of true hermaphroditism: a 40-year experience
      with conservative gonadal surgery.
AB  - PURPOSE: Little is known about long-term outcomes of conservative gonadal surgery
      in true hermaphroditism. We present our experience with evaluation and treatment
      of a large series of children with this rare form of ambiguous genitalia,
      focusing on gonadal structure and function before and after conservative gonadal
      surgery. MATERIALS AND METHODS: We retrospectively reviewed 33 consecutive
      patients with histologically confirmed true hermaphroditism treated at the
      Hopital des Enfants-Malades between 1965 and 2005. RESULTS: The most common
      karyotype of true hermaphrodites was 46,XX, constituting 82% of our series. The
      frequency of finding the SRY gene in 46,XX cases was 35%. Ovotestis was the most
      frequent finding (65%) and testis the rarest (9%). Ovarian tissue was more often
      found on the left side, and testicular tissue on the right side (p <0.05). Proper
      gonadal tissue was preserved in 28 cases. No gonadal tumors were detected during
      followup. Ovarian tissue remained normal, while testicular tissue gradually
      developed signs of dysgenesis in all biopsied cases, confirmed by
      endocrinological studies. However, testosterone production remained satisfactory
      in the majority of cases during followup. CONCLUSIONS: Diagnosis of true
      hermaphroditism is well defined and the condition can be recognized even
      prenatally. Conservative gonadal surgery is the procedure of choice after a
      diagnosis of true hermaphroditism. Continued followup is necessary because of the
      multiple psychological, gynecological and urological problems encountered
      postpubertally by these patients.

PMID- 17222671
TI  - Spermatocytic seminoma.

PMID- 17222672
TI  - Slow progressive loss of renal function due to arteriovenous fistula caused by
      renal biopsy.

PMID- 17222673
TI  - Immunotherapy for orthotopic murine bladder cancer using bacillus Calmette-Guerin
      recombinant protein Mpt-64.
AB  - PURPOSE: We investigated the efficacy of the recombinant bacillus Calmette-Guerin
      subunit protein vaccine Mpt-64 for inducing cytokine production and suppressing
      orthotopic bladder tumor growth in mice. MATERIALS AND METHODS: One mycobacteria
      candidate gene (Mpt-64) was cloned and ligated into eukaryotic expression
      vectors. The induction and efficiency of Mpt-64 protein expression were detected
      using Western blotting. Various doses of Mpt-64 proteins were instilled
      intravesically 6 times in 2 weeks after intravesical implantation of MBT-2 tumor
      cells in chemical injured urothelium. Systemic cytokine responses, tumor growth
      and cumulative survival rates were monitored. RESULTS: In vitro expression of
      recombinant Mpt-64 subunit protein was efficient in our system. Mice treated with
      100 and 200 microg Mpt-64 subunit proteins significantly inhibited orthotopic MBT
      2 tumor growth in C3H/HeN mice compared with that in control and 50 microg
      treatment groups in terms of the tumor taking rate, bladder tumor burden and
      mortality rate. Meanwhile, marked increased serum interferon-gamma with a limited
      but significant increase in serum interleukin-2 was observed in mice treated with
      100 and 200 microg Mpt-64 proteins compared with control and 50 microg treated
      groups. CONCLUSIONS: A highly immunopotent recombinant Mpt-64 subunit protein of
      bacillus Calmette-Guerin was produced and it elicited immune responses with a
      high serum interferon-gamma level, inhibited orthotopic tumor growth and
      prolonged survival in tumor bearing mice. Thus, intravesical immunogenic therapy
      using recombinant Mpt-64 protein may be an alternative bacillus Calmette-Guerin
      regimen for superficial bladder cancer.

PMID- 17222674
TI  - Selenomethionine induced transcriptional programs in human prostate cancer cells.
AB  - PURPOSE: We determined the effects of selenomethionine, the major organic
      selenium containing compound found in the diet and the form of selenium being
      used in the Selenium and Vitamin E Cancer Prevention Trial, on prostate cancer
      cells. MATERIALS AND METHODS: We assessed global transcript profiles of
      selenomethionine treated LNCaP using cDNA microarrays and compared them to those
      of cells treated with methylselenic acid, a direct precursor of methylselenol,
      which is the active form of selenium in vivo. RESULTS: After treatment with
      selenomethionine 2,336 unique genes showed expression changes of at least 1.5
      fold in at least 3 time points during 48 hours and 366 unique transcripts
      differed significantly between selenomethionine and methylselenic acid treated
      LNCaP. Approximately half of the 76 cell cycle regulated genes affected by
      selenomethionine were down-regulated and enriched for genes associated with the
      G2/M phase. Flow cytometry analysis showed that selenomethionine induced G2/M
      arrest in LNCaP at low concentrations. Selenomethionine also affected expression
      levels of 35 known androgen responsive genes and 18 of these transcripts showed
      changes that were the inverse of those seen after androgen stimulation. At high
      concentrations selenomethionine decreased prostate specific antigen promoter
      driven luciferase expression. CONCLUSIONS: Selenomethionine modulates transcript
      levels of genes involved in a number of biological processes, including cell
      cycle/apoptosis androgen signaling, signal transduction and transcriptional
      regulation. Although the pathways affected paralleled in many ways those that are
      modulated by methylselenic acid, distinct differences in transcript patterns and
      effects on cell cycle regulation suggest that different selenium compounds could
      exert unique effects in prostate cells.

PMID- 17222675
TI  - Atrial natriuretic peptide attenuates hypoxia induced chemoresistance in prostate
      cancer cells.
AB  - PURPOSE: Low tumor oxygenation (hypoxia) correlates with resistance to
      chemotherapeutic agents. We recently reported that in vitro hypoxia induced
      resistance to various anti-cancer drugs can be attenuated by nitric oxide mimetic
      agents. Natriuretic peptides are molecules that mediate their cellular effects by
      activating a signaling pathway similar to that activated by nitric oxide. In the
      current study we determined whether atrial natriuretic peptide is able to inhibit
      hypoxia induced chemoresistance in prostate carcinoma cells. MATERIALS AND
      METHODS: Reverse transcriptase-polymerase chain reaction and atrial natriuretic
      peptide binding studies were used to determine the presence and function of
      natriuretic peptide receptors on a panel of human cell lines as well as in tissue
      samples. Drug sensitivity assays of cell lines exposed to hypoxic or standard
      conditions were performed in the presence of various concentrations of atrial
      natriuretic peptide. RESULTS: These studies revealed the presence of the 3 known
      natriuretic peptide receptors A, B and C in PC-3 and DU-145 human prostate
      carcinoma cells (American Type Culture Collection, Manassas, Virginia) as well as
      in tissue samples of human prostate cancer. Atrial natriuretic peptide binding to
      these cells was unaffected by culture in 0.5% vs 20% O(2). Clonogenic assays
      revealed that incubation of these cells in 0.5% O(2) for 24 hours resulted in a
      subsequent 4 to 10-fold increase in their survival following 1-hour exposure to
      doxorubicin (Sigma) (12.5 microM) (p <0.001). While small concentrations of
      atrial natriuretic peptide (10(-7) to 10(-13) M) did not affect sensitivity to
      doxorubicin in cells incubated in 20% O(2), similar concentrations of atrial
      natriuretic peptide inhibited the survival of these cells incubated in 0.5% O(2)
      by up to 50% (p <0.006). Using the cyclic guanosine monophosphate dependent
      protein kinase G inhibitor KT5823 (15 microM) the chemosensitizing effect of
      atrial natriuretic peptide was abrogated. CONCLUSIONS: These results indicate the
      potential use of natriuretic peptides as adjuvants to chemotherapy for prostate
      cancer.

PMID- 17222676
TI  - Expression of major heat shock proteins in prostate cancer: correlation with
      clinicopathological outcomes in patients undergoing radical prostatectomy.
AB  - PURPOSE: We evaluated expression levels of major heat shock proteins in radical
      prostatectomy specimens to clarify the significance of heat shock protein
      expression in prostate cancer. MATERIALS AND METHODS: Expression levels of heat
      shock proteins 27, 70 and 90 in radical prostatectomy specimens from 172 patients
      with clinically organ confined prostate cancer who had not received neoadjuvant
      hormonal therapy were measured by immunohistochemical staining. Cell
      proliferative activities and apoptotic features in these specimens were
      investigated using Ki-67 immunostaining and TUNEL assay, respectively. These
      findings were analyzed with respect to several clinicopathological factors.
      RESULTS: Various levels of heat shock protein 27 expression were noted in all
      prostate cancer specimens. Expression levels of heat shock protein 27 in prostate
      cancer tissues was significantly associated with pathological stage, Gleason
      score, surgical margin status, lymph node metastasis and tumor volume but not
      with other parameters, including patient age, serum prostate specific antigen and
      perineural invasion. Similarly most prostate cancer tissues showed heat shock
      protein 70 and 90 expression. However, there was no significant correlation
      between expression levels of these 2 heat shock proteins and several
      clinicopathological factors examined. Cell proliferative activity in prostate
      cancer specimens was significantly associated with heat shock protein 27
      expression but not with that of heat shock proteins 70 and 90, while there was no
      significant correlation between the apoptotic index and the expression of these 3
      heat shock proteins. Furthermore, despite the lack of prognostic significance in
      heat shock proteins 70 and 90 expression, biochemical recurrence-free survival in
      patients with strong heat shock protein 27 expression in radical prostatectomy
      specimens was significantly lower than that in those with weak heat shock protein
      27 expression. However, multivariate analysis showed that strong heat shock
      protein 27 expression could not be an independent predictor of biochemical
      recurrence after radical prostatectomy. CONCLUSIONS: These findings suggest that,
      despite the limited significance of heat shock proteins 70 and 90 expression,
      heat shock protein 27 may be involved in the progression of prostate cancer. The
      expression level of heat shock protein 27 in prostate cancer tissue could be used
      as a useful predictor of biochemical recurrence in patients undergoing radical
      prostatectomy.

PMID- 17222677
TI  - Effect of Gosha-jinki-gan, a blended herbal medicine, on bladder activity in
      rats.
AB  - PURPOSE: We investigated the effect of the blended herbal medicine Gosha-jinki
      gan on bladder activity and the autonomic nervous system in rats. MATERIALS AND
      METHODS: A total of 42 female rats were divided into a control diet group of 21
      and a Gosha-jinki-gan diet group of 21. Rats in the control diet group were fed a
      standard diet, while animals in the Gosha-jinki-gan were fed a special diet
      containing 1.08% Gosha-jinki-gan (TJ107, Tsumura Co., Tokyo, Japan). After 4
      weeks 28 rats, including 14 in the control and 14 in the Gosha-jinki-gan group,
      underwent continuous cystometry with physiological saline or 0.1% acetic acid
      solution and bladder activity was recorded. The remaining 14 rats were
      anesthetized with halothane, and body weight, serum amino acid (glutamate and
      glycine) and plasma monoamine (noradrenaline, adrenaline, dopamine and serotonin)
      levels were measured. RESULTS: The amplitude of bladder contraction on continuous
      cystometry with physiological saline was lower in the Gosha-jinki-gan diet group
      than in the control diet group, and plasma dopamine and serotonin levels were
      also lower in the Gosha-jinki-gan group. When cystometry was done with 0.1%
      acetic acid, the interval between bladder contractions was shortened in the
      control and Gosha-jinki-gan groups. However, the interval and duration of bladder
      contractions were longer in the Gosha-jinki-gan than in the control group.
      CONCLUSIONS: These results suggest that Gosha-jinki-gan inhibits bladder activity
      by maintaining the balance of the sympathetic and parasympathetic nervous systems
      at a low level.

PMID- 17222678
TI  - Comparative evaluation of central muscarinic receptor binding activity by
      oxybutynin, tolterodine and darifenacin used to treat overactive bladder.
AB  - PURPOSE: We characterized muscarinic receptor binding in the mouse cerebral
      cortex after oral administration of anticholinergic agents used to treat
      overactive bladder. MATERIALS AND METHODS: Muscarinic receptors in the mouse
      cerebral cortex and bladder after oral administration of anticholinergic agents
      were measured using [(3)H]N-methylscopolamine. RESULTS: In vitro binding
      affinities of tolterodine and its metabolite 5-hydroxymethyl metabolite in the
      mouse cerebral cortex and bladder were considerably greater than those of
      oxybutynin and darifenacin. Also, muscarinic receptor binding affinity of
      oxybutynin and its metabolite N-desethyl-oxybutynin in the cerebral cortex
      compared with that in the bladder was 2 to 3 times higher, whereas that of
      tolterodine and 5-hydroxymethyl metabolite was approximately 2 times lower. Oral
      administration of oxybutynin (76.1 micromol/kg), tolterodine (6.31 micromol/kg)
      and darifenacin (59.1 micromol/kg) showed binding activity that was approximately
      equal to that of bladder muscarinic receptors. Oral administration of oxybutynin
      (76.1 micromol/kg) showed significant binding of cerebral cortical muscarinic
      receptors in mice, as indicated by about a 2-fold increase in K(d) values for
      specific [(3)H]N-methylscopolamine binding 0.5 and 2 hours later. On the other
      hand, tolterodine and darifenacin given at oral doses that would exert a similar
      extent of bladder receptor binding activity as oxybutynin showed only a low level
      of binding activity of central muscarinic receptors in mice. CONCLUSIONS:
      Significant binding of brain muscarinic receptors in mice was observed by the
      oral administration of oxybutynin but not tolterodine and darifenacin.

PMID- 17222679
TI  - Improvement in bladder storage function by tamsulosin depends on suppression of C
      fiber urethral afferent activity in rats.
AB  - PURPOSE: Alpha(1)-blockers improve voiding symptoms by decreasing prostatic and
      urethral smooth muscle tone. However, to our knowledge the mechanism underlying
      improvements in storage symptoms is not known. Topical application of
      prostaglandin E(2) to the rat lower urinary tract stimulates the micturition
      reflex. Using an animal model we investigated whether the alpha(1)-blocker
      tamsulosin (Astellas Pharma, Tokyo, Japan) acts on C-fiber afferent activity and,
      if so, the location of this effect. MATERIALS AND METHODS: To induce
      desensitization of C-fiber afferent activity resiniferatoxin (0.3 mg/kg) was
      subcutaneously injected in female Sprague-Dawley rats 2 days before experiments.
      Simultaneous recordings of urethral pressure and rhythmic bladder pressure were
      made with the rats under urethane anesthesia. Prostaglandin E(2) (0.4 mg/ml) was
      continuously administered intravesically or intraurethrally to rats pretreated
      with resiniferatoxin (resiniferatoxin rats) or rats without pretreatment
      (nonresiniferatoxin rats). We investigated the effects on the micturition reflex
      of intravenous (2.2 x 10(-1) to 2.2 x 10(3) nM/kg) or intrathecal (0.001 to 0.1
      nmol) administration of tamsulosin. RESULTS: The bladder contraction interval was
      markedly decreased after intravesical or intraurethral administration of
      prostaglandin E(2) in nonresiniferatoxin rats but it was unchanged in
      resiniferatoxin rats. This effect was antagonized by the EP1 receptor antagonist
      ONO-8711 (6-[(2S,3S)-3-(4-chloro-2-methylphenylsulfonylaminomethyl)
      bicyclo[2.2.2]octan-2-yl]-5Z-hexenoic acid). Intravenous administration of
      tamsulosin significantly increased the bladder contraction interval in
      nonresiniferatoxin rats receiving intraurethral prostaglandin E(2) but it had no
      effect on nonresiniferatoxin rats receiving intravesical prostaglandin E(2).
      Intrathecal administration of tamsulosin produced a slight and insignificant
      increase in the bladder contraction interval in nonresiniferatoxin rats receiving
      intraurethral prostaglandin E(2). CONCLUSIONS: These results suggest that
      prostaglandin E(2) enhances the micturition reflex through C-fiber afferents and
      tamsulosin had an inhibitory effect on the C-fiber urethral afferent nerves,
      thereby improving bladder storage function.

PMID- 17222680
TI  - Ca2+ regulation in detrusor smooth muscle from ovine fetal bladder after in utero
      bladder outflow obstruction.
AB  - PURPOSE: We characterized intracellular Ca(2+) regulation in fetal bladders
      following outflow obstruction by examining the Ca(2+) response to agonists in
      smooth muscle cells. MATERIALS AND METHODS: Severe bladder outflow obstruction
      was induced in male fetal sheep by placing a urethral ring and urachal ligation
      midway through gestation at 75 days. Fetuses were examined 30 days after surgery.
      Intracellular Ca(2+) in single smooth muscle cells isolated from the bladder wall
      was measured with epifluorescence microscopy using fura-2(AM) during exposure to
      agonists, such as carbachol and adenosine triphosphate, and to other activators,
      such as caffeine and KCl. RESULTS: Detrusor smooth muscle cells from obstructed
      bladders had resting intracellular Ca(2+) similar to that in sham operated
      controls. The maximal response to carbachol was decreased following obstruction
      (p <0.05). Construction of dose-response curves also demonstrated higher EC(50)
      (p <0.05). However, these changes were not mirrored by caffeine evoked Ca(2+)
      release, which was not significantly different between the obstruction group and
      sham operated controls. Kinetic analysis of carbachol transients further revealed
      an attenuated maximal rate of increase in obstructed bladders (p <0.01). The
      magnitude of intracellular Ca(2+) to purinergic neurotransmitter adenosine
      triphosphate was also found to be smaller in cells from obstructed bladders (p
      <0.05), although transmembrane influx by high K depolarization was not
      significantly affected. CONCLUSIONS: Muscarinic and purinergic pathways were down
      regulated in fetal detrusor muscle following outflow obstruction. These major
      functional receptors appeared to be more susceptible to obstruction than other
      Ca(2+) regulators. Their impairment may contribute to the compromised contractile
      function seen in in utero bladder outflow obstruction.

PMID- 17222681
TI  - Atorvastatin preserves renal function in chronic complete unilateral ureteral
      obstruction.
AB  - PURPOSE: The pleiotropic effects of hMG-CoA (3-hydroxy-3-metylglutaryl coenzyme
      A) reductase inhibitors may provide renal protection in chronic kidney disease.
      We examined whether atorvastatin administration preserved renal function in rats
      with chronic unilateral ureteral obstruction. MATERIALS AND METHODS: Renal
      clearance experiments were performed in sham operated rats and rats subjected to
      3 or 12-day unilateral ureteral obstruction. Hemodynamics parameters and urinary
      microalbumin levels from the obstructed kidney were also measured. The rats were
      maintained on a regular diet or the same diet but supplemented with atorvastatin
      (50 mg/kg daily). RESULTS: Atorvastatin administration did not alter plasma total
      cholesterol but it significantly decreased triglyceride levels. In sham operated
      and 3-day unilateral ureteral obstruction rats atorvastatin treatment did not
      have effects on the glomerular filtration rate or effective renal plasma flow and
      it also did not affect urinary microalbumin levels. In rats with 12-day
      unilateral ureteral obstruction the glomerular filtration rate but not effective
      renal plasma flow was significantly higher and urinary microalbumin was
      significantly lower in atorvastatin treated rats than in those without
      atorvastatin treatment. CONCLUSIONS: Atorvastatin treatment decreased
      microalbuminuria and helped preserve filtration function in chronic unilateral
      ureteral obstruction without altering plasma cholesterol levels, suggesting that
      pleiotropic renal protection is offered by this statin.

PMID- 17222682
TI  - Endothelium dependent relaxation in rabbit genital resistance arteries is
      predominantly mediated by endothelial-derived hyperpolarizing factor in females
      and nitric oxide in males.
AB  - PURPOSE: In nongenital arteries a sex difference has been postulated in the
      dominant endothelium-derived relaxant factor(s), eg nitric oxide, prostacyclin or
      endothelial-derived hyperpolarizing factor. Knowledge of endothelium-derived
      relaxant factor mechanisms in genital tissues could influence the development of
      novel treatments for sexual dysfunction. We compared nitric oxide and endothelial
      derived hyperpolarizing factor contributions to acetylcholine induced relaxation
      in the genital arteries of the 2 sexes. MATERIALS AND METHODS: Male dorsal and
      cavernous penile arteries, and female extravaginal and intravaginal arteries from
      New Zealand White rabbits were studied. Acetylcholine concentration-vasodilator
      response curves were constructed in the presence of the nitric oxide synthase
      inhibitor Nomega-nitro-L-arginine methyl ester, K(+) channel blockers (apamin and
      charybdotoxin) or a combination. Indomethacin was present throughout to exclude
      prostacyclins. RESULTS: Extravaginal artery relaxation was predominantly
      endothelial-derived hyperpolarizing factor induced. Apamin plus charybdotoxin
      decreased maximal relaxations from a mean +/- SEM of 77% +/- 4% to 23% +/- 3% in
      6 preparations (p <0.01). However, nitric oxide and endothelial-derived
      hyperpolarizing factor contributed to overall function. Dorsal artery relaxation
      was largely nitric oxide induced. Nomega-nitro-L-arginine methyl ester decreased
      maximal relaxations from 90% +/- 3% to 41% +/- 9% (p <0.001) with no endothelial
      derived hyperpolarizing factor involvement (p >0.05). In cavernous and
      intravaginal arteries nitric oxide and endothelial-derived hyperpolarizing factor
      contributed to acetylcholine induced relaxation, while nitric oxide predominated.
      Blocking nitric oxide synthase or K(+) channels indicated that myogenic tone and
      constitutive activity of endothelium-derived relaxant factors were present.
      Vasodilator nerve mediated responses were influenced by each with the former more
      effective. CONCLUSIONS: Vaginal inflow arteries showed a dominance of endothelial
      derived hyperpolarizing factor, contrasting with nitric oxide in penile arteries.
      Penile arteries followed the trend that endothelial-derived hyperpolarizing
      factor involvement increased with decreasing vessel caliber, while the reverse
      was demonstrated in female arteries.

PMID- 17222684
TI  - Re: Involvement of ubiquitination and sumoylation in bladder lesions induced by
      persistent long-term low dose ionizing radiation in humans and Re: DNA damage
      repair in bladder urothelium after the Chernobyl accident in Ukraine.

PMID- 17222685
TI  - Re: Ultrasound assessment of detrusor thickness in men--can it predict bladder
      outlet obstruction and replace pressure flow study?

PMID- 17222686
TI  - Re: High rate of vaginal erosions associated with the mentor ObTape.

PMID- 17222687
TI  - Re: Experience with 100 cases treated with botulinum-A toxin injections in the
      detrusor muscle for idiopathic overactive bladder syndrome refractory to
      anticholinergics.

PMID- 17222688
TI  - Re: Noninvasive methods of diagnosing bladder outlet obstruction in men. Part 2:
      Noninvasive urodynamics and combination of measures.

PMID- 17222689
TI  - Re: Nerve sparing open radical retropubic prostatectomy--does it have an impact
      on urinary continence?

PMID- 17222691
TI  - The innate antiviral response: new insights into a continuing story.

PMID- 17222692
TI  - Apoptosis during herpes simplex virus infection.
AB  - Herpes simplex virus (HSV) infection triggers apoptosis in infected cells.
      However, proteins synthesized later in infected cells prevent apoptotic cell
      death from ensuing. In vivo data showing that apoptosis accompanies herpes
      stromal keratitis and encephalitis suggest that apoptotic modulation plays a role
      in the development of herpetic disease. Tremendous progress has been made toward
      identifying the viral factors that are responsible for inducing and inhibiting
      apoptosis during infection. However, the mechanisms whereby they act are still
      largely unknown. Recent studies have illustrated a wide diversity in the cellular
      response to HSV-triggered apoptosis, emphasizing the importance of host factors
      in this process. Together, these findings indicate that apoptosis during HSV
      infection represents an important virus-host interaction process, which likely
      influences viral pathogenesis.

PMID- 17222693
TI  - The baculoviruses occlusion-derived virus: virion structure and function.

PMID- 17222694
TI  - Coupling of rotavirus genome replication and capsid assembly.
AB  - The Reoviridae family represents a diverse collection of viruses with segmented
      double-stranded (ds)RNA genomes, including some that are significant causes of
      disease in humans, livestock, and plants. The genome segments of these viruses
      are never detected free in the infected cell but are transcribed and replicated
      within viral cores by RNA-dependent RNA polymerase (RdRP). Insight into the
      replication mechanism has been provided from studies on Rotavirus, a member of
      the Reoviridae whose RdRP can specifically recognize viral plus (+) strand RNAs
      and catalyze their replication to dsRNAs in vitro. These analyses have revealed
      that although the rotavirus RdRP can interact with recognition signals in (+)
      strand RNAs in the absence of other proteins, the conversion of this complex to
      one that can support initiation of dsRNA synthesis requires the presence and
      partial assembly of the core capsid protein. By this mechanism, the viral
      polymerase can carry out dsRNA synthesis only when capsid protein is available to
      package its newly made product. By preventing the accumulation of naked dsRNA
      within the cell, the virus avoids triggering dsRNA-dependent interferon signaling
      pathways that can induce expression and activation of antiviral host proteins.

PMID- 17222695
TI  - Origin and evolution of 3'UTR of flaviviruses: long direct repeats as a basis for
      the formation of secondary structures and their significance for virus
      transmission.
AB  - The 3' untranslated regions (3'UTRs) of flaviviruses are reviewed and analyzed in
      relation to short sequences conserved as direct repeats (DRs). Previously,
      alignments of the 3'UTRs have been constructed for three of the four recognized
      flavivirus groups, namely mosquito-borne, tick-borne, and nonclassified
      flaviviruses (MBFV, TBFV, and NCFV, respectively). This revealed (1) six long
      repeat sequences (LRSs) in the 3'UTR and open-reading frame (ORF) of the TBFV,
      (2) duplication of the 3'UTR of the NCFV by intramolecular recombination, and (3)
      the possibility of a common origin for all DRs within the MBFV. We have now
      extended this analysis and review it in the context of all previous published
      analyses. This has been achieved by constructing a robust alignment between all
      flaviviruses using the published DRs and secondary RNA structures as "anchors" to
      reveal additional homologies along the 3'UTR. This approach identified nucleotide
      regions within the MBFV, NKV (no-known vector viruses), and NCFV 3'UTRs that are
      homologous to different LRSs in the TBFV 3'UTR and ORF. The analysis revealed
      that some of the DRs and secondary RNA structures described individually within
      each flavivirus group share common evolutionary origins. The 3'UTR of
      flaviviruses, and possibly the ORF, therefore probably evolved through multiple
      duplication of an RNA domain, homologous to the LRS previously identified only in
      the TBFV. The short DRs in all virus groups appear to represent the evolutionary
      remnants of these domains rather than resulting from new duplications. The
      relevance of these flavivirus DRs to evolution, diversity, 3'UTR enhancer
      function, and virus transmission is reviewed.

PMID- 17222696
TI  - Tropical Whitefly IPM Project.
AB  - The Tropical Whitefly IPM Project (TWFP) is an initiative of the Systemwide IPM
      Programme of the Consultative Group on International Agricultural Research
      (CGIAR), financed by the Department for International Development (DFID) of the
      United Kingdom, the Danish International Development Agency (DANIDA), the United
      States Department of Agriculture (USDA) and Agency for International Development
      (USAID), the Australian Centre for International Agricultural Research (ACIAR),
      and the New Zealand Agency for International Development (NZAID), to manage
      whitefly pests and whitefly-transmitted viruses in the Tropics. Participating
      CGIAR and other international centers include the Centre for International
      Tropical Agriculture (CIAT); the International Institute of Tropical Agriculture
      (IITA); The International Potato Centre (CIP); the Asian Vegetable Research and
      Development Centre (AVRDC); and the International Centre of Insect Physiology and
      Ecology (ICIPE), in close collaboration with the National Resources Institute
      (NRI-UK); national agricultural research institutions; agricultural universities;
      and advanced agricultural research laboratories in Africa, Asia, Europe, the
      Pacific Region, and the Americas. The TWFP was launched in 1996 as five separate
      but closely linked subprojects targeting: (1) Bemisia tabaci as a vector of
      viruses affecting cassava and sweet potato in sub-Saharan Africa (IITA, NRI, CIP,
      CIAT); (2) B. tabaci as a vector of viruses in mixed cropping systems of Mexico,
      Central America, and the Caribbean (CIAT); (3) B. tabaci as a vector of viruses
      in mixed cropping systems of eastern and southern Africa (ICIPE, AVRDC); (4) B.
      tabaci as a vector of viruses in mixed cropping systems of Southeast Asia
      (AVRDC); (5) Trialeurodes vaporariorum as a pest in mixed cropping systems of the
      Andean highlands (CIAT); and (6) whiteflies as pests of cassava in South America
      (CIAT). Diagnostic surveys conducted in Phase I (1997-2000) clearly showed that
      the two main whitefly pests in the Tropics are B. tabaci and, in the highlands,
      T. vaporariorum. Other whitefly species investigated by the TWFP included B. afer
      and Aleurotrachelus socialis. B. tabaci is the main vector of plant viruses
      inducing African cassava mosaic disease, sweet potato virus disease, bean golden
      mosaic disease, and many other diseases of horticultural crops, mainly tomato,
      hot and sweet peppers, squash, melon, and several other cucurbits. Genetic
      resistance was identified as the most important component of an IPM programme,
      followed by phytosanitary, cultural and legal measures. The two most important
      factors contributing to whitefly/virus epidemics were shown to be pesticide abuse
      and the use of virus-infected planting materials. Biological control is only
      effective in cropping systems with minimal or rational use of insecticides, and
      should be considered only as a complementary IPM strategy. Farmer education and
      technical assistance are considered the most critical steps toward the
      implementation of sustainable and economically viable IPM strategies in tropical
      countries affected by whitefly pests and whitefly-transmitted viruses.

PMID- 17222698
TI  - The role of the mitochondrion in sperm function: is there a place for oxidative
      phosphorylation or is this a purely glycolytic process?
AB  - We review here the current knowledge related to the metabolic pathways used by
      spermatozoa to meet their high demands for ATP. This is discussed with special
      emphasis on one of their key roles, motility. We believe that the controversy
      among glycolytic and oxidative phosphorylation supporters is artificial and, as
      it happens in many other cell types, the source of ATP is multiple and depends on
      external inputs.

PMID- 17222699
TI  - The role of mitochondrial function in the oocyte and embryo.
AB  - Mitochondria have long been known to be the powerhouses of the cell but they also
      contribute to redox and Ca2+ homeostasis, provide intermediary metabolites and
      store proapoptotic factors. Mitochondria have a unique behavior during
      development. They are maternally transmitted with little (if any) paternal
      contribution, and they originate from a restricted founder population, which is
      amplified during oogenesis. Then, having established the full complement of
      mitochondria in the fully grown oocyte, there is no further increase of the
      mitochondrial population during early development. The localization of
      mitochondria in the egg during maturation and their segregation to blastomeres in
      the cleaving embryo are strictly regulated. Gradients in the distribution of
      mitochondria present in the egg have the potential to give rise to blastomeres
      receiving different numbers of mitochondria. Such maternally inherited
      differences in mitochondrial distribution are thought to play roles in defining
      the long-term viability of the blastomere in some cases and embryonic axes and
      patterning in others. Mitochondria may also regulate development by a number of
      other means, including modulating Ca2+ signaling, and the production of ATP,
      reactive oxygen species, and intermediary metabolites. If the participation of
      mitochondria in the regulation of sperm-triggered Ca2+ oscillations is now well
      established, the role of other properties of mitochondrial function during
      development remain largely unexplored probably due to the difficulty of accessing
      the mitochondrial compartment in an embryo. Maintaining a functional complement
      of maternally derived mitochondria is vital for the early embryo. Mitochondrial
      dysfunction may not only compromise developmental processes but also trigger
      apoptosis in the embryo. This dual role for mitochondria (to maintain life or to
      commit to cell death) may well represent a quality control system in the early
      embryo that will determine whether the embryo proceeds further into development
      or is quickly eliminated.

PMID- 17222700
TI  - Mitochondrial DNA in the oocyte and the developing embryo.
AB  - Mitochondria play a primary role in cellular energetic metabolism, homeostasis,
      and death. They possess their own multicopy genome, which is maternally
      transmitted. Mitochondria are directly involved at several levels in the
      reproductive process since their functional status influences the quality of
      oocytes and contributes to the process of fertilization and embryonic
      development. This chapter discusses recent findings concerning mitochondrial DNA
      content and its expression during oogenesis, fertilization, and early embryonic
      development.

PMID- 17222701
TI  - Mitochondrial DNA and the mammalian oocyte.
AB  - In mammals, mitochondria and mitochondrial DNA (mtDNA) are transmitted through
      the female germ line. Mature oocytes contain at least 100,000 copies of mtDNA,
      organized at 1-2 copies per organelle. Despite the high genome copy number, mtDNA
      sequence variants are observed to segregate rapidly between generations, and this
      has led to the concept of a developmental bottleneck for the transmission of
      mtDNA. Ultrastructural investigations of primordial germ cells show that they
      contain approximately 10 mitochondria, suggesting that mitochondrial biogenesis
      is arrested during early embryogenesis, and that the mitochondria contributing to
      the germ cell precursors are simply apportioned from those present in the zygote.
      Thus, as few as 0.01% of the mitochondria in the oocyte actually contribute to
      the offspring of the next generation. Mitochondrial replication restarts in the
      migrating primordial germ cells, and mitochondrial numbers steadily increase to a
      few thousand in primordial oocytes. Genetic evidence from both heteroplasmic mice
      and human pedigrees suggests that segregation of mtDNA sequence variants is
      largely a stochastic process that occurs during the mitotic divisions of the germ
      cell precursors. This process is essentially complete by the time the primary
      oocyte population is differentiated in fetal life. Analysis of the distribution
      of pathogenic mtDNA mutations in the offspring of carrier mothers shows that risk
      of inheriting a pathogenic mutation increases with the proportion in the mother,
      but there is no bias toward transmitting more or less of the mutant mtDNAs. This
      implies that there is no strong selection against oocytes carrying pathogenic
      mutations and that atresia is not a filter for oocyte quality based on oxidative
      phosphorylation capacity. The large number of mitochondria and mtDNAs present in
      the oocyte may simply represent a genetic mechanism to ensure their distribution
      to the gametes and somatic cells of the next generation. If true, mtDNA copy
      number, and by inference mitochondrial number, may be the most important
      determinant of oocyte quality, not because of the effects on oocyte metabolism,
      but because too few would result in a maldistribution in the early embryo.

PMID- 17222702
TI  - Mitochondrial disease--its impact, etiology, and pathology.
AB  - Mitochondria are ubiquitous organelles that are intimately involved in many
      cellular processes, but whose principal task is to provide the energy necessary
      for normal cell functioning and maintenance. Disruption of this energy supply can
      have devastating consequences for the cell, organ, and individual. Over the last
      two decades, mutations in both mitochondrial DNA (mtDNA) and nuclear DNA have
      been identified as causative in a number of well-characterized clinical
      syndromes, although for mtDNA mutations in particular, this relationship between
      genotype and phenotype is often not straightforward. Despite this, a number of
      epidemiological studies have been undertaken to assess the prevalence of mtDNA
      mutations and these have highlighted the impact that mtDNA disease has on both
      the community and individual families. Although there has been considerable
      improvement in the diagnosis of mitochondrial disorders, disappointingly this has
      not been matched by developments toward effective treatment. Nevertheless, our
      understanding of mitochondrial biology is gathering pace and progress in this
      area will be crucial to devising future treatment strategies. In addition to
      mitochondrial disease, evidence for a central role of mitochondria in other
      processes, such as aging and neurodegeneration, is slowly accumulating, although
      their role in cancer remains controversial. In this chapter, we discuss these
      issues and offer our own views based on our cumulative experience of
      investigating and managing these diseases over the last 20 years.

PMID- 17222703
TI  - Cybrid models of mtDNA disease and transmission, from cells to mice.
AB  - Oxidative phosphorylation (OXPHOS) is the only mammalian biochemical pathway
      dependent on the coordinated assembly of protein subunits encoded by both nuclear
      and mitochondrial DNA (mtDNA) genes. Cytoplasmic hybrid cells, cybrids, are
      created by introducing mtDNAs of interest into cells depleted of endogenous
      mtDNAs, and have been a central tool in unraveling effects of disease-linked
      mtDNA mutations. In this way, the nuclear genetic complement is held constant so
      that observed effects on OXPHOS can be linked to the introduced mtDNA. Cybrid
      studies have confirmed such linkage for many defined, disease-associated
      mutations. In general, a threshold principle is evident where OXPHOS defects are
      expressed when the proportion of mutant mtDNA in a heteroplasmic cell is high.
      Cybrids have also been used where mtDNA mutations are not known, but are
      suspected, and have produced some support for mtDNA involvement in more common
      neurodegenerative diseases. Mouse modeling of mtDNA transmission and disease has
      recently taken advantage of cybrid approaches. By using cultured cells as
      intermediate carriers of mtDNAs, ES cell cybrids have been produced in several
      laboratories by pretreatment of the cells with rhodamine 6G before cytoplast
      fusion. Both homoplasmic and heteroplasmic mice have been produced, allowing
      modeling of mtDNA transmission through the mouse germ line. We also briefly
      review and compare other transgenic approaches to modeling mtDNA dynamics,
      including mitochondrial injection into oocytes or zygotes, and embryonic
      karyoplast transfer. When breakthrough technology for mtDNA transformation
      arrives, cybrids will remain valuable for allowing exchange of engineered mtDNAs
      between cells.

PMID- 17222704
TI  - The use of micromanipulation methods as a tool to prevention of transmission of
      mutated mitochondrial DNA.
AB  - The introduction of different micromanipulation techniques into reproductive and
      developmental biology has helped us not only to answer many essential biological
      questions but it is now evident that these techniques also have wide practical
      applications. In human-assisted reproduction, the most commonly used approach is
      the injection of a donor sperm into the oocyte cytoplasm--intracytoplasmic sperm
      injection. It is, however, speculated that with these techniques it would be also
      possible to improve the oocyte developmental potential especially in those cases
      when the quality of the cytoplasm is rather poor and thus its function is
      compromised. Another important application would be the elimination of mutated
      mitochondrial DNA (mtDNA) by transferring the nuclear material from an abnormal
      oocyte into a healthy donor oocyte cytoplast. Some of these techniques were
      already successfully tested in experimental animals, but it is evident that
      before their introduction into human medicine many questions must be answered,
      and we must be sure that these approaches are absolutely or almost absolutely
      safe. In our contribution, we will be specifically oriented to the nuclear
      (nuclear material) replacement approaches that could be potentially used to
      prevent the transmission of mutated mtDNA from mother to offspring. Because these
      techniques are very delicate, some training with oocytes from other species other
      than human is strongly recommended.

PMID- 17222705
TI  - Difficulties and possible solutions in the genetic management of mtDNA disease in
      the preimplantation embryo.
AB  - Families who have had a child die of a severe, maternally inherited mitochondrial
      DNA (mtDNA) disease are usually desperate to avoid having further affected
      children. Here we discuss the problems of applying classical genetic management
      to mtDNA diseases (Poulton and Turnbull, 2000) and the biology underlying these
      problems. We explain why these disorders have lagged so far behind the genetics
      revolution. We then outline the directions in which management is likely to
      develop, including the use of preimplantation genetic diagnosis (PGD).

PMID- 17222706
TI  - Impact of assisted reproductive technologies: a mitochondrial perspective of
      cytoplasmic transplantation.
AB  - Many of the assisted reproductive techniques associated with maternal aging,
      disease states, or implantation failure aim to correct poor developmental
      capacity. These techniques are highly invasive and require the exchange of
      nuclear or cytoplasmic material from a donor oocyte to compensate for
      deficiencies inherent in the affected individual. These techniques are based on
      the assumption that the cytoplasm of the donor oocyte can effectively substitute
      the necessary component(s) to enable development to proceed. Several studies have
      attempted to inject cytoplasm from "normal" (young) donors, into aged eggs, again
      assuming that beneficial components of the cytoplasm are transferred to restore
      developmental capacity. These invasive assisted reproduction technology (ART)
      procedures aim to eliminate chromosomal abnormalities, improve the quality of
      oocytes deficient in some important cytoplasmic factors necessary for maturation
      and/or subsequent development, and eliminate maternally inherited diseases
      (particularly mitochondrial myopathies). However, in order to develop such ART,
      understanding the processes involving mitochondrial DNA replication and
      transcription is imperative, as asynchrony between mitochondrial and nuclear
      genomes may cause problems in mitochondrial function, localization, and
      biogenesis.

PMID- 17222707
TI  - Nuclear transfer: preservation of a nuclear genome at the expense of its
      associated mtDNA genome(s).
AB  - Nuclear transfer technology has uses across theoretical and applied applications,
      but advances are restricted by continued poor success rates and health problems
      associated with live offspring. Development of reconstructed embryos is dependent
      upon numerous interlinking factors relating both to the donor cell and the
      recipient oocyte. For example, abnormalities in gene expression following somatic
      cell nuclear transfer (SCNT) have been linked with an inability of the oocyte
      cytoplasm to sufficiently epigenetically reprogram the nucleus. Furthermore,
      influences on the propagation of mitochondria and mitochondrial DNA (mtDNA) could
      be of great importance in determining the early developmental potential of NT
      embryos and contributing to their genetic identity. mtDNA encodes some of the
      subunits of the electron transfer chain, responsible for cellular ATP production.
      The remaining subunits and those factors required for mtDNA replication,
      transcription and translation are encoded by the nucleus, necessitating precise
      intergenomic communication. Additionally, regulation of mtDNA copy number, via
      the processes of mtDNA transcription and replication, is essential for normal
      preimplantation embryo development and differentiation. Unimaternal transmission
      following natural fertilization usually results in the presence of a single
      identical population of mtDNA, homoplasmy. Heteroplasmy can result if mixed
      populations of mtDNA genomes co-exist. Many abnormalities observed in NT embryos,
      fetuses, and offspring may be caused by deficiencies in OXPHOS, perhaps resulting
      in part from heteroplasmic mtDNA populations. Additionally, incompatibilities
      between the somatic nucleus and the cytoplast may be exacerbated by increased
      genetic divergence between the two genomes. It is important to ensure that the
      nucleus is capable of sufficiently regulating mtDNA, requiring a level of
      compatibility between the two genomes, which may be a function of evolutionary
      distance. We suggest that abnormal expression of factors such as TFAM and POLG in
      NT embryos will prematurely drive mtDNA replication, hence impacting on early
      development.

PMID- 17222708
TI  - Does a BRCA mutation plus tamoxifen equal hysterectomy?

PMID- 17222711
TI  - Integration of quantitative DCE-MRI and ADC mapping to monitor treatment response
      in human breast cancer: initial results.
AB  - PURPOSE: The objective of this study was to assess changes in the water apparent
      diffusion coefficient (ADC) and in pharmacokinetic parameters obtained from the
      fast-exchange regime (FXR) modeling of dynamic contrast-enhanced magnetic
      resonance imaging (DCE-MRI) during neoadjuvant chemotherapy in breast cancer.
      MATERIALS AND METHODS: Eleven patients with locally advanced breast cancer
      underwent MRI examination prior to and after chemotherapy but prior to surgery. A
      1.5-T scanner was used to obtain T1, ADC and DCE-MRI data. DCE-MRI data were
      analyzed by the FXR model returning estimates of K(trans) (volume transfer
      constant), v(e) (extravascular extracellular volume fraction) and tau(i) (average
      intracellular water lifetime). Histogram and correlation analyses assessed
      parameter changes post-treatment. RESULTS: Significant (P < .05) changes or
      trends towards significance (P < .10) were seen in all parameters except tau(i),
      although there was qualitative reduction in tau(i) values post-treatment. In
      particular, there was reduction (P < .035) in voxels with K(trans) values in the
      range 0.2-0.5 min(-1) and a decrease (P < .05) in voxels with ADC values in the
      range 0.99 x 10(-3) to 1.35 x 10(-3) mm2/s. ADC and v(e) were negatively
      correlated (r = -.60, P < .02). Parameters sensitive to water distribution and
      geometry (T(1), v(e), tau(i) and ADC) correlated with a multivariable linear
      regression model. CONCLUSION: The analysis presented here is sensitive to
      longitudinal changes in breast tumor status; K(trans) and ADC are most sensitive
      to these changes. Relationships between parameters provide information on water
      distribution and geometry in the tumor environment.

PMID- 17222712
TI  - Spatial and temporal resolution effects on dynamic contrast-enhanced magnetic
      resonance mammography.
AB  - We tested the hypothesis that partial volume effects due to poor in-plane
      resolution and/or low temporal resolution used in clinical dynamic contrast
      enhanced magnetic resonance imaging results in erroneous diagnostic information
      based on inaccurate estimates of tumor contrast agent extravasation and tested
      whether reduced encoding techniques can correct for dynamic data volume
      averaging. Image spatial resolution was reduced from 469 x 469 microm2 to those
      reported below by selecting a subset of k-space data. We then compared the top
      five K(trans)/V(T) "hot spots" obtained from the original data set, 469 x 469
      microm in-plane spatial resolution and an 18-s temporal resolution processed by
      fast Fourier transform (FFT), with values obtained from data sets having in-plane
      spatial resolutions of 938 x 938, 1875 x 1875 and 2500 x 2500 microm2 and a
      temporal resolution of 18 s, or data sets with temporal resolutions of 36, 54 and
      72 and a spatial resolution of 469 x 469 microm2, and found them to statistically
      differ from the parent data sets. We then tested four different post processing
      methods for improving the spatial resolution without sacrificing temporal
      resolution: zero-filled FFT, keyhole, reduced-encoding imaging by generalized
      series reconstruction (RIGR) and two-reference RIGR (TRIGR). The top five values
      of K(trans)/V(T) obtained from data sets, the in-plane spatial resolutions of
      which were improved to 469 x 469 microm2 by zero-filling FFT, Keyhole and RIGR,
      statistically differed from those obtained from the original 469 x 469 microm2
      FFT parent image data set. Only the 938 x 938 and 1875 x 1875 microm2 data sets
      reconstructed to 469 x 469 microm2 with TRIGR reconstruction method yielded
      values of the top five K(trans)/V(T) hot spots statistically the same as the
      original parent data set, 469 x 469 microm2 in-plane spatial and 18-s temporal
      resolution FFT. That is, partial volume effects from data sets of different in
      plane spatial resolution resulted in statistically different values of the top
      five K(trans)/V(T) hot spots relative to a high spatial and temporal resolution
      data set, and TRIGR reconstruction of these low resolution data sets to high
      resolution images provided statistically similar values with a savings in
      temporal resolution of 2 to 4 times.

PMID- 17222713
TI  - CORSICA: correction of structured noise in fMRI by automatic identification of
      ICA components.
AB  - When applied to functional magnetic resonance imaging (fMRI) data, spatial
      independent component analysis (sICA), a data-driven technique that addresses the
      blind source separation problem, seems able to extract components specifically
      related to physiological noise and brain movements. These components should be
      removed from the data to achieve structured noise reduction and improve any
      subsequent detection and analysis of signal fluctuations related to neural
      activity. We propose a new automatic method called CORSICA (CORrection of
      Structured noise using spatial Independent Component Analysis) to identify the
      components related to physiological noise, using prior information on the spatial
      localization of the main physiological fluctuations in fMRI data. As opposed to
      existing spectral priors, which may be subject to aliasing effects for long-TR
      data sets (typically acquired with TR >1 s), such spatial priors can be applied
      to fMRI data, regardless of the TR of the acquisitions. By comparing the proposed
      automatic selection to a manual selection performed visually by a human operator,
      we first show that CORSICA is able to identify the noise-related components for
      long-TR data with a high sensitivity and a specificity of 1. On short-TR data
      sets, we validate that the proposed method of noise reduction allows a
      substantial improvement of the signal-to-noise ratio evaluated at the cardiac and
      respiratory frequencies, even in the gray matter, while preserving the main
      fluctuations related to neural activity.

PMID- 17222714
TI  - Detecting functional connectivity in the resting brain: a comparison between ICA
      and CCA.
AB  - Independent component analysis (ICA) and cross-correlation analysis (CCA) are
      general tools for detecting resting-state functional connectivity. In this study,
      we jointly evaluated these two approaches based on simulated data and in vivo
      functional magnetic resonance imaging data acquired from 10 resting healthy
      subjects. The influence of the number of independent components (maps) on the
      results of ICA was investigated. The influence of the selection of the seeds on
      the results of CCA was also examined. Our results reveal that significant
      differences between these two approaches exist. The performance of ICA is
      superior as compared with that of CCA; in addition, the performance of ICA is not
      significantly affected by structured noise over a relatively large range. The
      results of ICA could be affected by the number of independent components if this
      number is too small, however. Converting the spatially independent maps of ICA
      into z maps for thresholding tends to overestimate the false-positive rate.
      However, the overestimation is not very severe and may be acceptable in most
      cases. The results of CCA are dependent on seeds location. Seeds selected based
      on different criteria will significantly affect connectivity maps.

PMID- 17222715
TI  - An improved temporal clustering analysis method applied to whole-brain data in
      fMRI study.
AB  - Temporal clustering analysis (TCA) has been proposed as a method to detect the
      brain responses of an fMRI time series when the time and location of the
      activation are completely unknown. But TCA is still incompetent in dealing with
      the time series of the whole brain due to the existence of many inactive pixels.
      If only active pixels are considered, the sensitivity of TCA will be improved
      greatly and it could be applied to the whole brain. In this study, some
      modifications were made to TCA to remove inactive pixels, and the applicability
      of the modified TCA to the whole brain was validated with a set of visual fMRI
      data. Based on the time series of the modified TCA, activations of the whole
      brain corresponding to the visual stimulation were detected. Compared with the
      previous TCA, the modified TCA method shows a significant improvement in the
      sensitivity to detect activation peaks of the whole brain.

PMID- 17222716
TI  - Echo-spacing optimization for the simultaneous measurement of reversible (R2')
      and irreversible (R2) transverse relaxation rates.
AB  - Accurate measurement of reversible (R2') and irreversible (R2) transverse
      relaxation rates plays a key role in various magnetic resonance imaging research
      and applications. Although optimization of echo spacing for a multiecho pulse
      sequence measuring a single exponential decay has been investigated, optimization
      in sequences such as Gradient-Echo Sampling of Free Induction Decay and Echo
      (GESFIDE), in which two echo trains are simultaneously measured to obtain both R2
      and R2', has not been reported. In this work, optimum echo spacings for the
      GESFIDE sequence are determined to improve the accuracy of measured relaxation
      parameters. Various relaxation rates and the number of acquired echoes are
      considered, as well as whether the receiver bandwidth is kept fixed or is varied
      with echo spacing. In the case of constant receiver bandwidth, results show that
      the echo train length approximately equal to T2* should be used for each echo
      train in GESFIDE to minimize uncertainty in R2 or R2'. If the receiver bandwidth
      is allowed to change with echo spacing in order to maximize the image signal-to
      noise ratio, the optimum echo train length will vary, generally increasing with
      the number of echoes.

PMID- 17222717
TI  - Performance of interventions with manipulator-driven real-time MR guidance:
      implementation and initial in vitro tests.
AB  - The purpose of this work was to implement and assess the performance of
      interventions inside a cylindrical magnetic resonance imaging (MRI) scanner with
      an MR-compatible manipulator system and manipulator-driven real-time MR guidance.
      The interventional system is based on a seven degree-of-freedom MR-compatible
      manipulator, which offers man-in-the-loop control either with a graphical user
      interface or with a master/slave device. The position and the orientation of the
      interventional tool are sent to an MR scanner for a manipulator-driven dynamic
      update of the imaging plane to track, visualize and guide the motion of an end
      effector. Studies on phantoms were performed with a cylindrical 1.5-T scanner
      using an operator-managed triggered gradient-recalled echo (GRE) or a computer
      managed dynamic True Fast Imaging with Steady Precession (TrueFISP). Targets were
      acquired with an accuracy of 3.2 mm and with an in-plane path orientation of 2.5
      degrees relative to the prescribed one. Path planning, including negotiation of
      obstacles and needle bending, was successfully performed. The signal-to-noise
      ratio (SNR) of TrueFISP was 25.3+/-2.1 when the manipulator was idle and was
      18.6+/-2.4 during its operation. The SNR of triggered GRE (acquired only when the
      manipulator was idle) was 61.3+/-1.8. In conclusion, this study shows the
      feasibility of performing manually directed interventions inside cylindrical MR
      scanners with real-time MRI.

PMID- 17222718
TI  - Maturation-dependent microstructure length scale in the corpus callosum of fixed
      rat brains by magnetic resonance diffusion-diffraction.
AB  - Techniques capable of assessing microstructure length scale are potentially
      useful in probing the integrity of biologic tissue at the microscopic level.
      Although the magnetic resonance (MR) diffusion-diffraction technique has been
      proposed for years, its realization in an undissected brain has not been reported
      on. In this study, validation of this method in a phantom simulating a series of
      repeated sheets of water with regular spacing was first performed. The same
      technique was applied to the corpus callosum of fixed rat brains of different
      ages (range, 21-84 days). The phantom was constructed with a pile of
      transparencies immersed in water doped with Gd-DTPA. The measured signal showed
      diffraction-like coherence peaks, the modulation of which was influenced by the
      gap distance and the center-to-center distance of the adjacent gaps. The measured
      distances were consistent with the actual values. In five 84-day-old rats, the
      diffusion length scale derived from the diffractogram was highly reproducible. In
      the course of brain maturation, the measured size decreased with age. Electron
      microscopy showed that axons on day 21 were smaller in diameter and less
      myelinated as compared with those on day 84. Progressive decrease in the
      diffusion length scale observed during brain maturation might reflect a gradual
      decrease in transmembrane permeability due to myelination. In conclusion, MR
      diffusion-diffraction can be observed in the corpus callosum of fixed rat brains.
      This technique might be useful in probing the status of myelination in the
      development of disease.

PMID- 17222719
TI  - The value of specific MRI features in the evaluation of suspected placental
      invasion.
AB  - OBJECTIVE: The objective of this study was to determine imaging features that may
      help predict the presence of placenta accreta, placenta increta or placenta
      percreta on prenatal MRI scanning. SUBJECTS AND METHODS: A retrospective review
      of the prenatal MR scans of 10 patients with a diagnosis of placenta accreta,
      placenta increta or placenta percreta made by pathologic and clinical reports and
      of 10 patients without placental invasion was performed. Two expert MRI readers
      were blinded to the patients' true diagnosis and were asked to score a total of
      17 MRI features of the placenta and adjacent structures. The interrater
      reliability was assessed using kappa statistics. The features with a moderate
      kappa statistic or better (kappa > .40) were then compared with the true
      diagnosis for each observer. RESULTS: Seven of the scored features had an
      interobserver reliability of kappa > .40: placenta previa (kappa = .83); abnormal
      uterine bulging (kappa = .48); intraplacental hemorrhage (kappa = .51);
      heterogeneity of signal intensity on T2-weighted (T2W) imaging (kappa = .61); the
      presence of dark intraplacental bands on T2W imaging (kappa = .53); increased
      placental thickness (kappa = .69); and visualization of the myometrium beneath
      the placenta on T2W imaging (kappa = .44). Using Fisher's two-sided exact test,
      there was a statistically significant difference between the proportion of
      patients with placental invasion and those without placental invasion for three
      of the features: abnormal uterine bulging (Rater 1, P = .005; Rater 2, P = .011);
      heterogeneity of T2W imaging signal intensity (Rater 1, P = .006; Rater 2, P =
      .010); and presence of dark intraplacental bands on T2W imaging (Rater 1, P =
      .003; Rater 2, P = .033). CONCLUSIONS: MRI can be a useful adjunct to ultrasound
      in diagnosing placenta accreta prenatally. Three features that are seen on MRI in
      patients with placental invasion appear to be useful for diagnosis: uterine
      bulging; heterogeneous signal intensity within the placenta; and the presence of
      dark intraplacental bands on T2W imaging.

PMID- 17222720
TI  - Error propagation model for microscopic magnetic resonance elastography shear
      wave images.
AB  - Microscopic magnetic resonance elastography is a high-resolution method for
      visualizing shear waves and assessing the biomechanical viscoelastic properties
      of small biological samples. In this work, we used error propagation to develop a
      simple analytical model that relates the signal-to-noise ratio of MR magnitude
      images to the variance in shear-wave maps collected using gradient-echo and spin
      echo phase-contrast pulse sequences. Our model predicts results for shear-wave
      images in phantoms, which match the experimentally observed phase variance within
      8%. This model can be used to optimize MR pulse sequences for elastography
      studies, as well as other phase-difference techniques in MRI.

PMID- 17222721
TI  - Noninvasive quantification of fluid mechanical energy losses in the total
      cavopulmonary connection with magnetic resonance phase velocity mapping.
AB  - A major determinant of the success of surgical vascular modifications, such as
      the total cavopulmonary connection (TCPC), is the energetic efficiency that is
      assessed by calculating the mechanical energy loss of blood flow through the new
      connection. Currently, however, to determine the energy loss, invasive pressure
      measurements are necessary. Therefore, this study evaluated the feasibility of
      the viscous dissipation (VD) method, which has the potential to provide the
      energy loss without the need for invasive pressure measurements. Two experimental
      phantoms, a U-shaped tube and a glass TCPC, were scanned in a magnetic resonance
      (MR) imaging scanner and the images were used to construct computational models
      of both geometries. MR phase velocity mapping (PVM) acquisitions of all three
      spatial components of the fluid velocity were made in both phantoms and the VD
      was calculated. VD results from MR PVM experiments were compared with VD results
      from computational fluid dynamics (CFD) simulations on the image-based
      computational models. The results showed an overall agreement between MR PVM and
      CFD. There was a similar ascending tendency in the VD values as the image spatial
      resolution increased. The most accurate computations of the energy loss were
      achieved for a CFD grid density that was too high for MR to achieve under current
      MR system capabilities (in-plane pixel size of less than 0.4 mm). Nevertheless,
      the agreement between the MR PVM and the CFD VD results under the same resolution
      settings suggests that the VD method implemented with a clinical imaging modality
      such as MR has good potential to quantify the energy loss in vascular geometries
      such as the TCPC.

PMID- 17222722
TI  - Improved wrist pannus volume measurement from contrast-enhanced MRI in rheumatoid
      arthritis using shuffle transform.
AB  - BACKGROUND: Contrast-enhanced MRI is of value in assessing rheumatoid pannus in
      the hand, but the images are not always easy to quantitate. OBJECTIVE: To develop
      and evaluate an improved measurement of volume of enhancing pannus (VEP) in the
      hand in human rheumatoid arthritis (RA). METHODS: MR images of the hand and wrist
      were obtained for 14 patients with RA at 0, 1 and 13 weeks. Volume of enhancing
      pannus was measured on images created by subtracting precontrast T1-weighted
      images from contrast-enhanced T1-weighted images using a shuffle transformation
      technique. Maximum intensity projection (MIP) and 3D volume rendering of the
      images were used as a guide to identify the pannus and any contrast-enhanced
      veins. RESULT: Visualisation of pannus was much improved following the shuffle
      transform. Between 0 weeks and 1 week, the mean value of the within-subject
      coefficient of variation (CoV) was 0.13 and the estimated total CoV was 0.15.
      There was no evidence of significant increased variability within the 13-week
      interval for the complete sample of patients. CONCLUSION: Volume of enhancing
      pannus can be measured reproducibly in the rheumatoid hand using 3D contrast
      enhanced MRI and shuffle transform.

PMID- 17222723
TI  - Osmotic and aging effects in caviar oocytes throughout water and lipid changes
      assessed by 1H NMR T1 and T2 relaxation and MRI.
AB  - By combining NMR relaxation spectroscopy and magnetic resonance imaging
      techniques, unsalted (us) and salted (s) caviar (Acipenser transmontanus) oocytes
      were characterized over a storage period of up to 90 days. The aging and the
      salting effects on the two major cell constituents, water and lipids, were
      separately assessed. T1 and T2 decays were interpreted by assuming a two-site
      exchange model. At Day 0, two water compartments that were not in fast exchange
      were identified by the T1 relaxation measurements on the us oocytes. In the s
      samples, T1 decay was monoexponential. During the time of storage, an increment
      of the free water amount was found for the us oocytes, ascribed to an increased
      metabolism. T1 and T2 of the s oocytes shortened as a consequence of the osmotic
      stress produced by salting. Selective images showed the presence of water endowed
      with different regional mobility that severely changed during the storage. Lipid
      T1 relaxation decays collected on us and s samples were found to be
      biexponential, and the T1 values lengthened during storage. In us and s oocytes,
      the increased lipid mobility with the storage was ascribed to lipolysis.
      Selective images of us samples showed lipids that were confined to the cytoplasm
      for up to 60 days of storage.

PMID- 17222724
TI  - MRI of tarantulas: morphological and perfusion imaging.
AB  - This paper describes a study performed to evaluate the feasibility of using a 1.5
      T whole-body magnetic resonance imaging (MRI) equipment, in combination with
      pharmacokinetic modeling, to obtain in vivo information about the morphology and
      perfusion of tarantulas (Eurypelma californicum). MRI was performed on three
      tarantulas using spin-echo sequences for morphological imaging and a rapid
      spoiled gradient-echo sequence for dynamic imaging during and after contrast
      medium (CM; Gd-DTPA) injection. Signal enhancement in dynamic measurements was
      evaluated with a pharmacokinetic two-compartment model. Spin-echo images showed
      morphological structures well. Dynamic images were of sufficient quality and
      allowed a model analysis of CM kinetics, which provides information about
      regional perfusion. In conclusion, morphological and dynamic contrast-enhanced
      MRI of tarantulas is feasible with a conventional clinical scanner. Studies of
      this kind are therefore possible without a dedicated high-field animal scanner.

PMID- 17222725
TI  - The observation and quantification of oil migration and binding in sediments
      using T2 magnetic resonance imaging.
AB  - Magnetic resonance imaging (MRI) makes use of the interactions between atomic
      nuclei and an external, strong, magnetic field to image the distribution of these
      nuclei through a substance. In this study, proton MRI has been used to indicate
      the presence of oil in sediment. Using a multiecho spin-echo acquisition
      sequence, images of relative oil density, and hence concentration, and of the
      magnetic resonance relaxation rate, T2, were produced. T2, which is greatly
      influenced by molecular motion, was equated to binding between the oil and the
      sediment, thus, providing an almost real-time "description" of all aspects of the
      oil-sediment interaction including motion of the oil. The interactions among
      three sediments from the Tay Estuary (East Coast of Scotland) and three crude
      oils (Fulmar, Forties and Venezuelan) are discussed. Observation of changes in
      images of oil density and changes in T2, using spread sheets, allow both rates of
      diffusion of the oil into the sediment and changes in the binding of the oil to
      the sediment to be calculated. Both the Forties and Fulmar oils move more rapidly
      than the Venezuelan oil in all of the sediments examined, while the strength of
      binding is sediment dependent. Thus, the ability of MRI to distinguish between
      the rates of flow of the oils into the sediment and the strengths of interaction
      between the various sediments and oils is demonstrated.

PMID- 17222726
TI  - Texture analysis of brain MRI evidences the amygdala activation by nociceptive
      stimuli under deep anesthesia in the propofol-formalin rat model.
AB  - Magnetic resonance images of rat brain were analyzed by texture analysis in order
      to study the effects of a nociceptive stimulation (formalin test) under propofol
      deep anesthesia. Changes of the texture in different cerebral brain areas
      acquired before and after stimulation were checked. Our statistical analysis of
      texture shows that these changes were present only in the amygdala, in agreement
      with the facts already known about the unconscious memorization of nociceptive
      stimuli.

PMID- 17222727
TI  - Diagnostic and therapeutic challenges in patients with coexistent chronic
      obstructive pulmonary disease and chronic heart failure.
AB  - Chronic obstructive pulmonary disease (COPD) and heart failure (CHF) are common
      conditions. The prevalence of COPD ranges from 20% to 30% in patients with CHF.
      The diagnosis of CHF can remain unsuspected in patients with COPD, because
      shortness of breath is attributed to COPD. Measurement of plasma B-type
      natriuretic peptide (BNP) levels helps to uncover unsuspected CHF in patients
      with COPD and clinical deterioration. Noninvasive assessment of cardiac function
      may be preferable to BNP to uncover unsuspected left ventricular (LV) systolic
      dysfunction in patients with stable COPD. Patients with COPD or CHF develop
      skeletal muscle alterations that are strikingly similar. Functional intolerance
      correlates with severity of skeletal muscle alterations but not with severity of
      pulmonary or cardiac impairment in COPD and CHF, respectively. Improvement of
      pulmonary or cardiac function does not translate into relief of functional
      intolerance in patients with COPD or CHF unless skeletal muscle alterations
      concomitantly regress. The mechanisms responsible for skeletal muscle alterations
      are incompletely understood in COPD and in CHF. Disuse and low-level systemic
      inflammation leading to protein synthesis/degradation imbalance are likely to
      contribute. The presence of COPD impacts on the treatment of CHF, as COPD is
      still viewed as a contraindication to beta-blockade. Therefore, COPD often
      deprives patients with CHF due to LV systolic dysfunction of the most beneficial
      pharmacologic intervention. A large body of data indicates that patients with
      COPD tolerate well selective beta-blockade that should not be denied to CHF
      patients with concomitant COPD.

PMID- 17222728
TI  - Long-term outcomes after management of restenosis or thrombosis of drug-eluting
      stents.
AB  - OBJECTIVES: The purpose of this study was to examine the outcomes of patients who
      developed coronary in-stent restenosis (ISR) or stent thrombosis (STH) inside
      drug-eluting stents (DES). BACKGROUND: Drug-eluting stents have markedly reduced
      the incidence of restenosis. However, when restenosis occurs within a DES, its
      optimal management remains unclear. METHODS: We retrospectively analyzed clinical
      and angiographic data from 92 patients who underwent revascularization for ISR (n
      = 84) or STH (n = 8) within a DES at our institution. Regular follow-ups were
      available up to 2 years. We recorded the occurrence of major adverse cardiac
      events (MACE), defined as deaths from all causes, myocardial infarction (MI), or
      target lesion revascularization (TLR), among patients treated by the "DES
      sandwich" technique or by other treatment methods. RESULTS: In-hospital MACE
      included 1 periprocedural MI and 2 deaths. Over a mean follow-up of 15 +/- 6
      months, the overall rates of death, MI, and TLR were 8.7%, 2.2%, and 30.6%,
      respectively. By actuarial analysis, the 12-month TLR and MACE rates were 28.2%
      and 42.9%, respectively. CONCLUSIONS: Current treatments of ISR or STH in DES are
      associated with a high long-term rate of MACE.

PMID- 17222729
TI  - Persistent activation of nuclear factor kappa-B signaling pathway in patients
      with unstable angina and elevated levels of C-reactive protein evidence for a
      direct proinflammatory effect of azide and lipopolysaccharide-free C-reactive
      protein on human monocytes via nuclear factor kappa-B activation.
AB  - OBJECTIVES: Our study investigated: 1) the contribution of nuclear factor kappa-B
      (NF-kappaB) signaling pathway to the enhanced inflammatory response observed in
      unstable angina (UA) patients with elevated levels of C-reactive protein (CRP);
      and 2) whether CRP may have direct proinflammatory effects via NF-kappaB
      activation. BACKGROUND: Unstable angina patients with elevated CRP have enhanced
      inflammatory response and increased risk of persistent instability, myocardial
      infarction, and death. METHODS: We studied 28 patients with history of UA and
      persistently elevated CRP (>3 mg/l) followed for 24 months and free of symptoms
      for at least 6 months (group 1), 14 patients with history of UA and low CRP
      (group 2), and 24 patients with chronic stable angina and low CRP (group 3).
      Peripheral blood monocytes were analyzed for spontaneous NF-kappaB activation and
      interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha production. To assess
      the direct proinflammatory effects of CRP, monocytes from 8 healthy subjects were
      stimulated in vitro with increasing doses of CRP (5 to 10 to 25 microg/ml),
      lipopolysaccharide (LPS) (1 to 10 ng/ml), or both. RESULTS: Spontaneous NF-kappaB
      activation in vivo was demonstrated in 82% of group 1 versus 14% of group 2 and
      21% of group 3 patients (p < 0.001). Interleukin-6 and TNF-alpha production was
      significantly correlated with the NF-kappaB activation status (r = 0.55, p <
      0.001 and r = 0.53, p = 0.006, respectively). Patients with NF-kappaB activation
      had recurrence of acute coronary events (60% vs. 28%; p = 0.017). C-reactive
      protein induced a significant but modest in vitro NF-kappaB activation in human
      monocytes (p = 0.002). Coincubation with LPS produced a greater-than-additive
      response (p < 0.01 vs. CRP and LPS alone). CONCLUSIONS: Nuclear factor kappa-B
      activation might represent a mechanism by which CRP amplifies and perpetuates the
      inflammatory component of acute coronary syndromes and influences the clinical
      outcome.

PMID- 17222730
TI  - The role of C-reactive protein activation of nuclear factor kappa-B in the
      pathogenesis of unstable angina.

PMID- 17222731
TI  - Cardiovascular features of heart failure with preserved ejection fraction versus
      nonfailing hypertensive left ventricular hypertrophy in the urban Baltimore
      community: the role of atrial remodeling/dysfunction.
AB  - OBJECTIVES: The purpose of this study was to identify cardiovascular features of
      patients with heart failure with preserved ejection fraction (HFpEF) that differ
      from those in individuals with hypertensive left ventricular hypertrophy (HLVH)
      of similar age, gender, and racial background but without failure. BACKGROUND:
      Heart failure with preserved ejection fraction often develops in HLVH patients
      and involves multiple abnormalities. Clarification of changes most specific to
      HFpEF may help elucidate underlying pathophysiology. METHODS: A cross-sectional
      study comparing HFpEF patients (n = 37), HLVH subjects without HF (n = 40), and
      normotensive control subjects without LVH (n = 56). All subjects had an EF of
      >50%, sinus rhythm, and insignificant valvular or active ischemic disease, and
      groups were matched for age, gender, and ethnicity. Comprehensive echo-Doppler
      and pressure analysis was performed. RESULTS: The HFpEF patients were
      predominantly African-American women with hypertension, LVH, and obesity. They
      had vascular and systolic-ventricular stiffening and abnormal diastolic function
      compared with the control subjects. However, most of these parameters either
      individually or combined were similarly abnormal in the HLVH group and poorly
      distinguished between these groups. The HFpEF group had quantitatively greater
      concentric LVH and estimated mean pulmonary artery wedge pressure (20 mm Hg vs.
      16 mm Hg) and shorter isovolumic relaxation time than the HLVH group. They also
      had left atrial dilation/dysfunction unlike in HLVH and greater total epicardial
      volume. The product of LV mass index and maximal left atrial (LA) volume best
      identified HFpEF patients (84% sensitivity, 82% specificity). CONCLUSIONS: In an
      urban, principally African American, cohort, HFpEF patients share many
      abnormalities of systolic, diastolic, and vascular function with nonfailing HLVH
      subjects but display accentuated LVH and LA dilation/failure. These latter
      factors may help clarify pathophysiology and define an important HFpEF population
      for clinical trials.

PMID- 17222732
TI  - Diagnostic value of contrast-enhanced magnetic resonance imaging and single
      photon emission computed tomography for detection of myocardial necrosis early
      after acute myocardial infarction.
AB  - OBJECTIVES: This study sought to evaluate the diagnostic value of contrast
      enhanced magnetic resonance imaging (CMR) and single-photon emission computed
      tomography (SPECT) for detection of myocardial necrosis after acute myocardial
      infarction (AMI). BACKGROUND: Single-photon emission computed tomography is
      widely accepted in the clinical setting for detection and estimation of
      myocardial infarction. Contrast-enhanced magnetic resonance imaging offers
      technical advantages and is therefore a promising new method for identification
      of infarcted tissue. METHODS: Seventy-eight patients with AMI were examined by
      CMR and SPECT 7 days after percutaneous coronary intervention. Contrast-enhanced
      magnetic resonance imaging and SPECT images were scored for presence and location
      of infarction using a 17-segment model. Results were compared with the peak
      troponin T level, electrocardiographic, and angiographic findings. RESULTS: Acute
      myocardial infarction was detected significantly more often by CMR than SPECT
      (overall sensitivity: 97% vs. 87%; p = 0.008). Sensitivity of CMR was superior to
      SPECT in detecting small infarction as assessed by the peak troponin T level <3.0
      ng/ml (92 vs. 69%; p = 0.03), and infarction in non-anterior location (98% vs.
      84%; p = 0.03). Non-Q-wave infarctions were more likely to be detected by CMR
      (sensitivity 85% vs. 46%; p = 0.06). While CMR offered high sensitivity for
      detection of AMI irrespective of the infarct-related artery, SPECT was less
      sensitive, particularly within the left circumflex artery territory. CONCLUSIONS:
      Contrast-enhanced magnetic resonance imaging is superior to SPECT in detecting
      myocardial necrosis after reperfused AMI because CMR detects small infarcts that
      were missed by SPECT independent of the infarct location. Thus, CMR is attractive
      for accurate detection and assessment of the myocardial infarct region in
      patients early after AMI.

PMID- 17222733
TI  - A novel two-dimensional echocardiographic image analysis system using artificial
      intelligence-learned pattern recognition for rapid automated ejection fraction.
AB  - OBJECTIVES: We sought to test the hypothesis that a novel 2-dimensional
      echocardiographic image analysis system using artificial intelligence-learned
      pattern recognition can rapidly and reproducibly calculate ejection fraction
      (EF). BACKGROUND: Echocardiographic EF by manual tracing is time consuming, and
      visual assessment is inherently subjective. METHODS: We studied 218 patients (72
      female), including 165 with abnormal left ventricular (LV) function. Auto EF
      incorporated a database trained on >10,000 human EF tracings to automatically
      locate and track the LV endocardium from routine grayscale digital cineloops and
      calculate EF in 15 s. Auto EF results were independently compared with manually
      traced biplane Simpson's rule, visual EF, and magnetic resonance imaging (MRI) in
      a subset. RESULTS: Auto EF was possible in 200 (92%) of consecutive patients, of
      which 77% were completely automated and 23% required manual editing. Auto EF
      correlated well with manual EF (r = 0.98; 6% limits of agreement) and required
      less time per patient (48 +/- 26 s vs. 102 +/- 21 s; p < 0.01). Auto EF
      correlated well with visual EF by expert readers (r = 0.96; p < 0.001), but
      interobserver variability was greater (3.4 +/- 2.9% vs. 9.8 +/- 5.7%,
      respectively; p < 0.001). Visual EF was less accurate by novice readers (r =
      0.82; 19% limits of agreement) and improved with trainee-operated Auto EF (r =
      0.96; 7% limits of agreement). Auto EF also correlated with MRI EF (n = 21) (r =
      0.95; 12% limits of agreement), but underestimated absolute volumes (r = 0.95;
      bias of -36 +/- 27 ml overall). CONCLUSIONS: Auto EF can automatically calculate
      EF similarly to results by manual biplane Simpson's rule and MRI, with less
      variability than visual EF, and has clinical potential.

PMID- 17222734
TI  - The prognostic value of normal exercise myocardial perfusion imaging and exercise
      echocardiography: a meta-analysis.
AB  - OBJECTIVES: The purpose of this work was to determine the prognostic value of
      normal exercise myocardial perfusion imaging (MPI) tests and exercise
      echocardiography tests, and to determine the prognostic value of these imaging
      modalities in women and men. BACKGROUND: Exercise MPI and exercise
      echocardiography provide prognostic information that is useful in the risk
      stratification of patients with suspected coronary artery disease (CAD). METHODS:
      We searched the PubMed, Cochrane, and DARE databases between January 1990 and May
      2005, and reviewed bibliographies of articles obtained. We included prospective
      cohort studies of subjects who underwent exercise MPI or exercise
      echocardiography for known or suspected CAD, and provided data on primary
      outcomes of myocardial infarction (MI) and cardiac death with at least 3 months
      of follow-up. Secondary outcomes (unstable angina, revascularization procedures)
      were abstracted if provided. Studies performed exclusively in patients with CAD
      were excluded. RESULTS: The negative predictive value (NPV) for MI and cardiac
      death was 98.8% (95% confidence interval [CI] 98.5 to 99.0) over 36 months of
      follow-up for MPI, and 98.4% (95% CI 97.9 to 98.9) over 33 months for
      echocardiography. The corresponding annualized event rates were 0.45% per year
      for MPI and 0.54% per year for echocardiography. In subgroup analyses, annualized
      event rates were <1% for each MPI isotope, and were similar for women and men.
      For secondary events, MPI and echocardiography had annualized event rates of
      1.25% and 0.95%, respectively. CONCLUSIONS: Both exercise MPI and exercise
      echocardiography have high NPVs for primary and secondary cardiac events. The
      prognostic utility of both modalities is similar for both men and women.

PMID- 17222735
TI  - Assessing mature technology: what is the effect of high-quality risk
      stratification evidence with exercise echocardiography and single-photon emission
      computed tomography imaging?

PMID- 17222736
TI  - Postmortem long QT syndrome genetic testing for sudden unexplained death in the
      young.
AB  - OBJECTIVES: This study sought to determine the spectrum and prevalence of long QT
      syndrome (LQTS)-associated mutations in a large cohort of autopsy-negative sudden
      unexplained death (SUD). BACKGROUND: Potentially heritable arrhythmia syndromes
      may explain a significant proportion of SUD in the young. Here, comprehensive
      postmortem LQTS genetic testing was performed in a cohort of SUD cases. METHODS:
      From September 1998 to March 2004, 49 cases of SUD (30 male patients, average age
      at death 14.2 +/- 10.9 years) were referred by medical examiners/coroners to Mayo
      Clinic's Sudden Death Genomics Laboratory. Using polymerase chain reaction,
      denaturing high-performance liquid chromatography, and direct DNA sequencing,
      open reading frame/splice site mutational analysis was conducted for all 8 genes
      implicated in the pathogenesis of either LQTS (LQT1 to LQT6) or multisystem
      disorders involving either QT or QU prolongation. RESULTS: Ten LQTS-associated
      mutations (4 novel) were discovered in 10 SUD cases (20%, 8 female patients,
      average age at death 18.0 +/- 11.8 years). The LQTS susceptibility mutations LQT1
      (5), LQT2 (3), and LQT3 (2) were far more common among women (8 of 18, 44%) than
      men (2 of 30, 6.7%, p < 0.008). The activities at the time of SUD included sleep
      (5), exertion (2), auditory arousal (1), and undetermined (2). Sudden death was
      the sentinel event in two-thirds of the cases. CONCLUSIONS: In this cardiac
      channel-focused molecular autopsy investigation of SUD, over one-third of
      decedents harbored a putative cardiac channel mutation: 7 previously reported to
      host mutations in the RyR2-encoded calcium release channel and now 10 with LQTS
      susceptibility mutations. Accordingly, postmortem cardiac channel genetic testing
      should be pursued in the evaluation of autopsy-negative SUD.

PMID- 17222737
TI  - Can a message from the dead save lives?

PMID- 17222738
TI  - Catheter-based transcoronary myocardial hypothermia attenuates arrhythmia and
      myocardial necrosis in pigs with acute myocardial infarction.
AB  - OBJECTIVES: This study evaluated the efficacy of catheter-based transcoronary
      myocardial hypothermia (CTMH) in pigs with acute myocardial ischemia. BACKGROUND:
      Although it has been suggested that hypothermia therapy can attenuate myocardial
      necrosis, few applications have been accepted for clinical use. METHODS: This
      study comprises 2 substudies. In both studies, pigs underwent 60 min of coronary
      occlusion and 180 min of reperfusion. In study 1, after 15 min of coronary
      occlusion with an over-the-wire-type balloon (OTWB), pigs in the hypothermia
      group (H) (n = 13) were directly infused with 4 degrees C saline into the
      coronary artery through the OTWB wire lumen (2.5 ml/min) for 60 min. Pigs in the
      normothermia group (N) (n = 15) received the same amount of 36.5 degrees C
      saline. In study 2, pigs in the hypothermia-reperfusion group (HR) (n = 5) were
      infused with 4 degrees C saline through the infusion catheter (8 ml/min) for 30
      min with a later start (60 min after coronary occlusion), whereas simple
      reperfusion was used for the reperfusion group (R) (n = 6). RESULTS: Catheter
      based transcoronary myocardial hypothermia was successful in both studies. In
      study 1, CTMH significantly decreased ventricular arrhythmia and the ratio of
      necrosis to ischemic risk area (H: 9 +/- 2%; N: 36 +/- 4%; p < 0.0001) with a
      significant reduction of enzyme leaks. In study 2, CTMH tended to reduce the
      ratio of necrosis (HR: 33 +/- 2%; R: 45 +/- 5%; p = 0.08). In both studies, CTMH
      significantly suppressed the increase of 8-iso-prostaglandin F(2alpha) while
      preserving the coronary flow reserve. CONCLUSIONS: Catheter-based transcoronary
      myocardial hypothermia reduced myocardial necrosis while preserving coronary flow
      reserve, due, in part, to attenuation of oxidative stress.

PMID- 17222739
TI  - Cold cardioplegia for acute infarction a viable adjunct to reperfusion therapy?

PMID- 17222740
TI  - Coronary artery calcification and changes in atheroma burden in response to
      established medical therapies.
AB  - OBJECTIVES: This study sought to determine the relationship between coronary
      calcification and plaque progression in response to established medical
      therapies. BACKGROUND: Coronary calcification correlates with the extent of
      atherosclerosis and predicts clinical outcome. METHODS: Atheroma volume was
      determined in serial intravascular ultrasound pullbacks in matched arterial
      segments of 776 patients with angiographic coronary artery disease. A calcium
      grade at baseline was assigned for each image (total 28,876) (0 = no calcium, 1 =
      calcium with acoustic shadowing <90 degrees and 2 = calcium with shadowing >90
      degrees). Patients with a calcium index (average of calcium scores in a pullback)
      below versus above the median were compared with regard to plaque burden and
      progression. RESULTS: Patients with a high calcium index were older (59 vs. 54
      years, p < 0.001), more likely to be male (80% vs. 68%, p < 0.001), and more
      likely to have a history of hypertension (71% vs. 64%, p = 0.03). These patients
      had a greater percentage atheroma volume (PAV) (45% vs. 34%, p < 0.001), total
      atheroma volume (TAV) (210 vs. 151 mm3, p < 0.001), and percentage of images with
      maximal plaque thickness >0.5 mm (93% vs. 72%, p < 0.001). The continuous rate of
      change in PAV (1.1 +/- 0.4% vs. 0.8 +/- 0.4%, p = 0.34) and TAV (1.7 +/- 2.1% vs.
      -0.1 +/- 2.2%, p = 0.37) was similar in patients with a lower and higher calcium
      index, respectively. A lower calcium index was associated with a higher rate of
      patients showing substantial change in atheroma burden (at least 5% change in
      PAV, 70% vs. 53%, p < 0.001). CONCLUSIONS: Calcific plaques are more resistant to
      undergoing changes in size in response to systemic interventions targeting
      atherosclerotic risk factors.

PMID- 17222741
TI  - Atherosclerosis regression, vascular remodeling, and plaque stabilization.

PMID- 17222742
TI  - Alpha2cDel322-325 and beta1Arg389 adrenergic polymorphisms are not associated
      with reduced left ventricular ejection fraction or increased left ventricular
      volume.

PMID- 17222743
TI  - Cost-effectiveness of upstream versus selective glycoprotein IIb/IIIa inhibitors
      for acute coronary syndromes.

PMID- 17222745
TI  - Two new Tetramitus species (Heterolobosea, Vahlkampfiidae) from cold aquatic
      environments.
AB  - Characterisation of the protists of cold environments provides important
      background for assessing the effects of climate change on microbial communities.
      Tetramitus angularis n. sp., from aquatic environments in Iceland and
      Switzerland, is the first vahlkampfiid recognised to have a characteristic
      Tetramitus flagellate stage combined with pre-formed excystment pores, which are
      not typical of this genus. T. angularis amoebae have a typical vahlkampfiid
      locomotive form and contain prominent lipid inclusions. Flagellates have a collar
      and cytostome, and can be mono- to multi-nucleate with corresponding change in
      cell shape from cylindrical to ellipsoidal and variable number of flagella. Cysts
      are round to semi-angular and have 2-5 pores closed by protruding, translucent
      plugs. A second organism, T. parangularis n. sp. from Alaska, has similar cysts
      but a flagellate stage has not been recognised; ITS sequence divergence is
      consistent with species criteria in the Vahlkampfiidae. Phylogenetic analysis of
      sequence data for the 5.8S rDNA region clusters the new spp. with T. rostratus,
      T. entericus and T. waccamawensis.

PMID- 17222746
TI  - Molecular identification of free-living amoebae of the Vahlkampfiidae and
      Acanthamoebidae isolated in Arizona (USA).
AB  - Sediment samples from rivers, canals and lakes in Arizona (USA) were cultured for
      free-living amoebae at three different incubation temperatures (22, 37 and 40
      degrees C). Isolates belonging to the Vahlkampfiidae were identified by
      sequencing the PCR-amplified ITS1, 5.8S and ITS2 rDNA. With this molecular method
      three Naegleria spp. were identified, N. gruberi sensu stricto, N. australiensis
      and N. tihangensis. Also a strain each of Willaertia magna and Vahlkampfia avara
      were identified. Three samples yielded two new Tetramitus spp. of which the
      closest relative is T. ovis. Many Acanthamoeba strains were also isolated. The
      genotype of these strains was identified using Acanthamoeba-specific primers
      (JDP1 and JDP2) amplifying a part of the SSUrDNA and sequencing with an internal
      primer (892c). Five of the Acanthamoeba isolates belong to genotype T5 (A.
      lenticulata), while five are genotype T4.

PMID- 17222747
TI  - International Society of Geriatric Oncology (SIOG) recommendations for the
      adjustment of dosing in elderly cancer patients with renal insufficiency.
AB  - A SIOG taskforce was formed to discuss best clinical practice for elderly cancer
      patients with renal insufficiency. This manuscript outlines recommended dosing
      adjustments for cancer drugs in this population according to renal function.
      Dosing adjustments have been made for drugs in current use which have
      recommendations in renal insufficiency and the elderly, focusing on drugs which
      are renally eliminated or are known to be nephrotoxic. Recommendations are based
      on pharmacokinetic and/or pharmacodynamic data where available. The taskforce
      recommend that before initiating therapy, some form of geriatric assessment
      should be conducted that includes evaluation of comorbidities and polypharmacy,
      hydration status and renal function (using available formulae). Within each drug
      class, it is sensible to use agents which are less likely to be influenced by
      renal clearance. Pharmacokinetic and pharmacodynamic data of anticancer agents in
      the elderly are needed in order to maximise efficacy whilst avoiding unacceptable
      toxicity.

PMID- 17222748
TI  - The role of cytotoxic therapy with hematopoietic stem cell transplantation in the
      therapy of acute myeloid leukemia in children: an evidence-based review.
AB  - Clinical research examining the role of hematopoietic stem cell transplantation
      (SCT) in the therapy of acute myeloid leukemia (AML) in children is presented and
      critically evaluated in this systematic evidence-based review. Specific criteria
      were used for searching the published literature and for grading the quality and
      strength of the evidence and the strength of the treatment recommendations.
      Treatment recommendations based on the evidence are presented in the table
      entitled "Summary of Treatment Recommendations Made by the Expert Panel for
      Pediatric Acute Myeloid Leukemia" and were reached unanimously by a panel of
      experts in AML. The identified priority areas of needed future research in
      pediatric AML include: What is the role of risk group stratification, including
      the role of cytogenetics, in selection of patients for allogeneic SCT, especially
      those in first CR? What is the appropriate timing and use of alternative donor
      SCT, given that matched unrelated donor SCT appears to yield outcomes equivalent
      to matched related donor SCT? What is the role of reduced intensity SCT
      (including the use of fludarabine-based preparative regimens) and/or other
      immunomodulatory approaches to maximize the graft-versus-leukemic effect? and
      What is the role of biologically targeted agents (ie, tyrosine kinase inhibitors,
      farnesyl transferase inhibitors, Flt-3 inhibitors, etc) in the treatment of AML,
      including induction, consolidation, conditioning regimens, and after SCT?

PMID- 17222749
TI  - Clinical utility of autopsy after hematopoietic stem cell transplantation.
AB  - Autopsy is the gold standard for establishing the cause of death. We present
      results of the largest retrospective review of complete autopsies of subjects
      after hematopoietic stem cell transplantation to better define the role of the
      autopsy in discovering a missed diagnosis. We reviewed the medical chart and
      autopsy records of 111 patients who had undergone hematopoietic stem cell
      transplantation from July 1986 to June 2003 from a single center. We compared the
      cause of death as charted by the clinical team with data obtained from postmortem
      chart review and autopsy reports. Of 29 (26%) cases when the premortem and
      postmortem major diagnoses did not agree, only 4 (4%) autopsy records provided
      data that might have led to the initiation of new treatments, and none of these
      diagnoses would be missed today with more sensitive and specific diagnostics and
      improved supportive care. Although autopsies after transplantation can be
      important educational, research, and epidemiologic tools and provide an emotional
      benefit to patient's families, in our series they rarely provided missed
      diagnoses that would alter the management of subsequent patients. Improvements in
      noninvasive tests for relapse or occult infections may further erode the role of
      autopsies in discovering missed diagnoses.

PMID- 17222750
TI  - What's past is prologue: lessons learned and the need for further development of
      allogeneic hematopoietic stem cell transplantation for renal cell carcinoma.

PMID- 17222751
TI  - Hematopoietic stem cell recipients do not develop post-transplantation immune
      tolerance to antigens present on minimal residual disease.
AB  - The immune environment present after allogeneic hematopoietic stem cell
      transplantation (HSCT) contributes to the control of leukemia. Our laboratory has
      demonstrated in a murine model that vaccination of recipients after
      transplantation with recipient tumor vaccines does not exacerbate graft-versus
      host disease but does induce meaningful graft-versus-tumor effects. We previously
      demonstrated that part of the reason for the lack of graft-versus-host disease
      from post-transplantation vaccination is due to gradual acquisition of tolerance
      or unresponsiveness to recipient immunodominant minor histocompatibility antigens
      that are ubiquitously expressed in the recipient. However, our prior studies have
      not critically addressed the question of whether a similar process of acquisition
      of unresponsiveness to or tolerance of antigens present on minimal residual
      disease also occurs. The present study tested the hypothesis that
      unresponsiveness to antigens present on minimal residual disease present at the
      time of HSCT would also occur. The answer to this question would have a
      significant effect on the potential efficacy of post-transplantation tumor
      vaccines. In a murine model of major histocompatibility complex matched, minor
      histocompatibility antigen mismatched HSCT (C3.SW female donors and C57BL/6
      female recipients), we tested whether transplant recipients would acquire
      unresponsiveness to antigens present on small numbers of residual
      leukemia/lymphoma cells. We employed a male C57BL/6 lymphoid malignancy with an
      immunoglobulin/c-myc oncogene in these studies using as a model of tumor
      restricted antigen the well-characterized male (HY) antigen system present only
      on the tumor but not present as ubiquitous minor antigens in the recipient. After
      HSCT, recipients did not mount immune responses to the ubiquitously distributed
      immunodominant recipient strain H7 minor histocompatibility antigen, but did
      retain the capacity to mount significant T cell responses to HY antigens present
      on small numbers of HY+ tumor cells present at transplantation. Additional
      studies using small numbers of nonmalignant recipient male B cells or dendritic
      cells as models of minimal residual disease also demonstrated that the transplant
      recipients retained their capacity to mount anti-HY T cell responses. After HSCT,
      recipients may retain the capacity to mount effective T cell responses to
      antigens present on minimal residual disease and still acquire relative tolerance
      to ubiquitously distributed immunodominant minor antigens that are related to
      graft-versus-host disease.

PMID- 17222753
TI  - Pharmacokinetics of once-daily IV busulfan as part of pretransplantation
      preparative regimens: a comparison with an every 6-hour dosing schedule.
AB  - In pretransplantation therapy busulfan is typically given every 6 hours. We
      infused busulfan once daily at 130 mg/m2 for 4 days, performing pharmacokinetic
      analyses on plasma concentration-time data (n = 60 patients) on days 1, 3, and/or
      4. Mean (percent coefficient of variation) maximum concentration, volume of
      distribution, half-life, and clearance were 3.6 microg/mL (13.8%), 22.6 L/m2
      (20.2%), 2.73 hours (27.5%), and 109 mL/min/m2 (26%), respectively. The mean
      (percent coefficient of variation) and median daily areas under the curve were
      4873 (21.8%) and 4871 microM x minute. Intrapatient variability in day-to-day
      estimated clearance was <20%, without day-to-day drug accumulation. The
      pharmokinetic parameters were compared with those from 47 patients given
      intravenous busulfan at approximately 0.8 mg/kg (approximately 32 mg/m2) every 6
      hours. We conclude that there is (1) a dose proportionality based on mean and
      median areas under the curve, (2) unchanged estimated clearance with a 4-fold
      increase in dose and a 2.5-fold difference in dosing rate, (3) negligible
      variability in dose-to-dose pharmacokinetics and negligible interdose
      accumulation with once-daily administration, and (4) no change in pharmokinetic
      parameter(s) with concomitant use of imidazole antifungals, oral contraceptives,
      or phenytoin. In summary, intravenous busulfan has highly predictable, linear
      pharmacokinetics from 32 mg/m2 (approximately 0.8 mg/kg) to 130 mg/m2
      (approximately 3.2 mg/kg). Further, once-daily intravenous busulfan dosing is
      convenient, favoring its more widespread application.

PMID- 17222752
TI  - An essential role for IFN-gamma in regulation of alloreactive CD8 T cells
      following allogeneic hematopoietic cell transplantation.
AB  - We previously found that CD8 T cells from IFN-gamma gene knockout (GKO) donors
      induce more severe lethal GVHD compared with CD8 T cells from wild-type (WT)
      donors in fully MHC-mismatched strain combinations. In this study, we
      investigated the mechanisms by which IFN-gamma inhibits GVHD in a parent --> F1
      (B6 --> B6D2F1) allogeneic HCT (allo-HCT) model. IFN-gamma was strongly
      protective against GVHD in this parent --> F1 haplotype-mismatched allo-HCT
      model. Irradiated B6D2F1 mice that received GKO B6 CD4-depleted splenocytes
      developed lethal GVHD with severe lung and liver injury, whereas those receiving
      a similar cell population from WT B6 donors survived long term. Donor CD8 cells
      showed rapid activation, accelerated cell division, and reduced/delayed
      activation-induced cell death in allogeneic recipients in which donor cells were
      incapable of producing IFN-gamma. In consequence, the numbers of
      activated/effector (ie, CD25+, CD62L-, and CD44(high)) donor CD8 T cells in the
      recipients of GKO allo-HCT significantly exceeded those in mice receiving WT allo
      HCT. These data show that IFN-gamma negatively regulates the CD8 T cell response
      by inhibiting cell division and promoting cell death and suggest that blockade of
      IFN-gamma could augment the severity of GVHD in patients undergoing allo-HCT.

PMID- 17222754
TI  - Advance care planning in patients undergoing hematopoietic cell transplantation.
AB  - Few data are available on the prevalence of advance care planning (ACP) in
      patients undergoing hematopoietic cell transplantation (HCT). We surveyed adult
      patients pre-HCT to ascertain completion of various elements of ACP. We also
      reviewed medical records for documentation of discussions regarding ACP and for
      the presence of written advance directives. Evaluable surveys were returned by
      155 of 335 patients (46%) who underwent HCT during the study period; we obtained
      permission for medical record review from 137 of these 155 survey respondents
      (88%). We found that 69% of the respondents reported having designated a health
      care proxy, 44% had completed a living will, 61% had prepared an estate will, and
      63% had discussed their wishes regarding life support with family and friends. In
      contrast, only 16% had discussed their wishes regarding life support with their
      clinicians. Documentation of discussions between clinicians and patients
      regarding most elements of ACP was rare. Written advance directives were present
      in the charts of 54 patients (39%). ACP was more common in older, college
      educated, and allogeneic transplant patients. Even though ACP was more prevalent
      among this sample than in the general population, its use still could be
      enhanced, given the high risks of decisional incapacity and death that HCT
      patients face.

PMID- 17222755
TI  - Treatment of adenovirus disease in stem cell transplant recipients with
      cidofovir.
AB  - Invasive adenovirus (AdV) disease is fatal in >50% of allogeneic hematopoietic
      stem cell transplant (SCT) recipients. Treatment with cidofovir may improve
      outcomes based on in vitro susceptibility data and case reports. Six consecutive
      cases of invasive AdV disease treated with cidofovir were reviewed among 84
      allogeneic adult SCT recipients (incidence, 7.1%). Cidofovir was administered
      intravenously at 5 mg/kg per dose (1-7 doses). All patients received intravenous
      immune globulin. Blood AdV DNA levels (viral loads, VLs) were monitored with a
      real-time quantitative polymerase chain reaction assay. Published reports of
      cidofovir treatment of AdV disease in SCT recipients were critically reviewed.
      The primary manifestations of AdV disease were hepatitis (n = 3), colitis (n =
      2), and nephritis (n = 1). All patients had detectable AdV VLs, with peak values
      from 5 x 10(5) to 2 x 10(8) copies/mL. All patients received CD34+ selected
      grafts (n = 3) and/or had graft-versus-host disease (n = 4) and had CD4 counts
      <100 cells/mm3. Only 1 of 5 patients (20%) who received >or=2 doses of cidofovir
      died with active AdV disease. Four patients exhibited improvement within days of
      treatment with cidofovir as documented by clinical criteria and declines in AdV
      VLs (without a change in immunosuppression). In contrast, 1 patient treated late
      after onset of AdV disease died after 1 dose of cidofovir. In our review of 70
      published cases treated with >or=2 doses of cidofovir, 13 (19%) died from AdV
      disease. In conclusion, early treatment of AdV disease with cidofovir inhibits
      viral replication in vivo and reduces mortality in allogeneic SCT recipients
      compared with historical data.

PMID- 17222756
TI  - Double unrelated reduced-intensity umbilical cord blood transplantation in
      adults.
AB  - Umbilical cord blood (UBC) stem cells are a useful stem cell source for patients
      without matched related or unrelated donors. Adult transplantation with single
      UBC units is associated with high transplantation-related mortality (TRM). In
      most cases, mortality is due to infection related to slow engraftment and
      immunoincompetence. In this study, we used a reduced-intensity conditioning
      regimen of fludarabine, melphalan, and antithymocyte globulin followed by 2
      partially matched UBC units. The UBC units were a 4/6 HLA match or better with
      each other and with the patient and achieved a minimum precryopreservation cell
      dose of 3.7 x 10(7) nucleated cells/kg. A total of 21 patients (median age, 49
      years) were treated. The median time to an absolute neutrophil count > 0.5 x
      10(9)/L was 20 days, and the median time to an unsupported platelet count > 20 x
      10(9)/L was 41 days. Two patients experienced primary graft failure and underwent
      a second UBC transplantation. One patient had a late graft failure. Acute graft
      versus-host disease (GVHD) grade II-IV occurred in 40% of patients. The 100-day
      TRM was 14%, and the 1-year disease-free survival was 67%. Mixed chimerism was
      associated with a higher risk of chronic GVHD. Our findings indicate that adult
      patients can tolerate double UBC transplantation well and achieve sustained
      antitumor responses using this reduced-intensity conditioning regimen.

PMID- 17222757
TI  - Allogeneic bone marrow transplantation from unrelated human T-cell leukemia virus
      I-negative donors for adult T-cell leukemia/lymphoma: retrospective analysis of
      data from the Japan Marrow Donor Program.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) from an HLA
      matched related donor has been suggested to improve the poor prognosis of adult T
      cell leukemia/lymphoma (ATLL). However, the infusion of HTLV-I-infected cells
      from HTLV-I-positive related donors could lead to the development of donor
      derived ATLL under immunosuppressive conditions. Although most ATLL patients lack
      a suitable HLA-matched related donor and require an HTLV-I-negative unrelated
      donor, little information is currently available regarding the outcome of
      unrelated bone marrow transplantation (UBMT) for ATLL. To evaluate the role of
      UBMT in treating ATLL, we retrospectively analyzed data from 33 patients with
      ATLL treated by UBMT through the Japan Marrow Donor Program (JMDP). Overall
      survival (OS), progression-free survival, and cumulative incidence of disease
      progression and progression-free mortality at 1 year after UBMT were 49.5%,
      49.2%, 18.6%, and 32.3%, respectively. Multivariate analysis identified recipient
      age as an independent prognostic factor for OS (P = .044). Patients age >or=50
      years who showed nonremission at transplantation tended to have higher rates of
      treatment-related mortality. Our observations suggest that UBMT could represent a
      feasible treatment option for ATLL patients and warrant further investigation
      based on these risk factors.

PMID- 17222758
TI  - Risk factors for developing human herpesvirus 6 (HHV-6) reactivation after
      allogeneic hematopoietic stem cell transplantation and its association with
      central nervous system disorders.
AB  - We prospectively evaluated the incidence of human herpesvirus 6 (HHV-6) DNAemia
      after allogeneic hematopoietic stem cell transplantation (HSCT) using
      quantitative plasma real-time polymerase chain reaction. Of 46 recipients of bone
      marrow or peripheral blood stem cell transplantation (BMT/PBSCT) from related (n
      = 11) or unrelated donors (n = 22), and cord blood transplantation (CBT) from
      unrelated donors (n = 13), 22 (47.8%) developed HHV-6 DNAemia. HHV-6 DNA levels
      ranged from 200 to 200,000 copies/mL of plasma, and HHV-6 DNAemia was observed
      significantly more frequently after CBT than after BMT/PBSCT (92.3% vs 30.3%; P <
      .001). Multivariate analyses identified CBT (vs BMT/PBSCT), HLA mismatches
      between recipient and donor, and low anti-HHV-6 IgG titer before transplantation
      as the only risk factors for developing HHV-6 DNAemia. Three patients developed
      central nervous system (CNS) disorders with detectable HHV-6 DNA in the
      cerebrospinal fluid; all of these patients simultaneously developed HHV-6
      DNAemia. These results suggest that HHV-6 DNAemia is frequently observed after
      allogeneic HSCT, especially in patients with the aforementioned risk factors.
      Thus, together with the assessment of risk factors, monitoring of HHV-6 DNAemia
      could be a useful asset in diagnosing HHV-6-associated CNS disorders.

PMID- 17222759
TI  - Allogeneic stem cell transplantation with T cell-depleted grafts for
      lymphoproliferative malignancies.
AB  - In non-Hodgkin lymphoma allogeneic stem cell transplantation (SCT) can be
      curative, but with standard dose conditioning patients may have substantial
      morbidity and mortality from graft-versus-host disease (GVHD); for aggressive
      malignancies, reduced intensity conditioning may result in higher recurrence.
      Patients with advanced follicular lymphoma (n = 12), transformed B cell
      malignancy (n = 11), and non-CD30+T cell lymphomas (n = 17) responsive to
      chemotherapy who had an HLA-identical sibling were offered T cell depleted
      (CAMPATH-1 G or H antibodies) SCT. Conditioning was with ablative doses of
      chemotherapy or radiotherapy. Before SCT, patients with follicular lymphoma had a
      median of 3 treatment courses, and those with transformed B cell and those
      diagnosed with T cell non-Hodgkin lymphoma had 2 (range, 1-3). At SCT the median
      age was 46 years (range, 21-59 years) and the number of CD34+ cells infused was
      2.85 x 10(6)/kg. All patients showed engraftment but 7 patients (17.5%) developed
      GVHD. In total 12 subjects expired of transplant-related causes (n = 6) or from
      disease recurrence. One-year transplant-related mortality was 15%. There was no
      difference in survival across diagnostic groups. At a median of 1051 days, 70%
      survived and 68% are without disease. By reducing the incidence and severity of
      GVHD, patients can tolerate myeloablative doses of chemotherapy satisfactorily.
      This has resulted in low treatment-related mortality and adequate protection from
      disease recurrence.

PMID- 17222760
TI  - Treatment of relapsed acute leukemia after allogeneic transplantation: a single
      center experience.
AB  - Relapsed acute leukemia after allogeneic transplantation has a poor prognosis and
      most reports have focused on the role of second transplantations in relapsed
      patients. We report our single-institution experience on the management of
      relapsed acute leukemia after allogeneic transplantation. We aimed to describe
      the outcome of relapsed acute leukemia after allogeneic transplantation at our
      institution and investigate whether maneuvers intended to augment donor T cell
      allogeneic reactivity were associated with durable graft-versus-leukemia effects.
      We analyzed 310 patients with acute leukemia who received allogeneic
      hematopoietic progenitor cell transplants from HLA-matched donors between 1982
      and 2005 (229 with acute myelogenous leukemia, 81 with acute lymphoblastic
      leukemia). Mean post-transplant follow-up was 5 years (range, 0.5-22 years).
      Factors associated with relapse incidence, therapy for relapse, response to
      treatment, and post-relapse survival were assessed. One hundred of 310 patients
      (32%) with acute leukemia relapsed after transplantation, including 28 of 81
      patients (35%) with acute lymphoblastic leukemia and 72 of 229 (31%) with acute
      myelogenous leukemia at a median of 136 days after transplantation. Median post
      relapse survival periods were 51 days for the 69 patients who received
      chemotherapy/supportive care, 84 days for 11 recipients of donor lymphocyte
      infusions, 303 days for 13 recipients of second transplants, and 442 days for 7
      patients treated with interferon-alpha and granulocyte-macrophage colony
      stimulating factor. A multivariable Cox regression analysis indicated that a
      longer time to relapse after transplantation, peripheral blood as source of stem
      cells, and initial post-relapse therapy with cytokines, donor lymphocyte
      infusions, or second transplants were associated with improved post-relapse
      survival (P <.001, <.001, and .025). The outlook for patients with post
      transplant relapse of acute leukemia is extremely poor; currently, no single
      therapy consistently results in durable remissions. Our study highlights the need
      for clinical trials in this area. Therapy with granulocyte-macrophage colony
      stimulating factor and interferon-alpha-2b is promising and will be pursued in a
      prospective trial at our center.

PMID- 17222762
TI  - Transplantation's greatest challenges: advances in chronic graft-versus-host
      disease.
AB  - Clinical research into chronic graft-versus-host disease (GVHD) lags behind that
      in other areas in the field. Interest in chronic GVHD has increased significantly
      in recent years for various reasons, including advances in biotechnology, a
      perceived increase in the incidence of chronic GVHD, and decreased regimen
      related mortality, resulting in a new emphasis on quality of life and absence of
      disability as endpoints of major significance in transplantation survivors. In
      this overview, we address 3 key areas related to chronic GVHD that hold the
      highest promise for major advances in the near future: pathobiology, response
      criteria, and therapy.

PMID- 17222766
TI  - Dendritic cells in transplantation and immune-based therapies.
AB  - Dendritic cells (DCs) are specialized, bone marrow-derived leukocytes critical to
      the onset of both innate and adaptive immunity. The divisions of labor among
      distinct human DC subtypes achieve the most effective balance between steady
      state tolerance and the induction of innate and adaptive immunity against
      pathogens, tumors, and other insults. Maintenance of tolerance in the steady
      state is an active process involving resting or semimature DCs. Breakdowns in
      this homeostasis can result in autoimmunity. Perturbation of the steady state
      should first lead to the onset of innate immunity mediated by rapid responders in
      the form of plasmacytoid and monocyte-derived DC stimulators and natural killer
      (NK) and NK T-cell responders. These innate effectors then provide additional
      inflammatory cytokines, including interferon-gamma, which support the activation
      and maturation of resident and circulating populations of DCs. These are critical
      to the onset and expansion of adaptive immunity, including Th1, Th2, and
      cytotoxic T-lymphocyte responses. Rodent models are now revealing important data
      about distinct DC precursors, homeostasis of tissue-resident DCs, and DC turnover
      in response to inflammation and pathological conditions like graft-versus-host
      disease. The use of defined DC subtypes to stimulate both innate and adaptive
      immunity, either in combination or in a prime-boost vaccine sequence, may prove
      most useful clinically by harnessing both effector cell compartments.

PMID- 17222765
TI  - Lymphoid reconstruction and vaccines.
AB  - Allogeneic HSCT is the most reliable, robust, and effective cell-based biotherapy
      currently available to pediatric and adult patients with hematologic
      malignancies. The central role of donor-derived lymphocytes in mediating an
      effective antitumor effect, preventing and controlling opportunistic infections,
      and causing GVHD is well documented in animal experiments and human trials. The
      profound lymphopenia after conditioning regimens coupled with molecular tools to
      distinguish host versus donor cells provides investigators a window into immune
      recovery after allogeneic HSCT. Serial analyses of T cell subsets linking
      immunophenotype with function have revealed the kinetics of donor-derived T cell
      recovery after allografting and provided insights into ways the immune system can
      be manipulated to augment the graft-versus-tumor (GVT) effect without inducing
      GVHD. As this review demonstrates, investigators are not limited to being passive
      observers of this immune reconstitution; rather, we have an opportunity to shape
      the allografted T cells repertoire to selectively augment immune function.

PMID- 17222772
TI  - Philadelphia chromosome-negative myeloproliferative disorders: biology and
      treatment.
AB  - The Philadelphia chromosome (Ph)-negative myeloproliferative disorders (MPDs)
      include essential thrombocythemia (ET), idiopathic myelofibrosis (IMF), and
      polycythemia vera (PV). All of these disorders are clonal hematologic
      malignancies originating at the level of the pluripotent hematopoietic stem cell.
      Recently, activating mutations of the intracellular cytokine-signaling molecule
      JAK2 have been identified in > 90% of patients with PV and in 50% of those with
      IMF and ET. In addition, a mutation of the thrombopoietin receptor, MPLW515L, has
      been documented in some patients with IMF. Both mutations activate JAK-STAT
      signaling pathways and likely play a role in disease progression. Both ET and PV
      are associated with prolonged clinical courses associated with frequent
      thrombotic and hemorrhagic events, and progression to myelofibrosis and acute
      leukemia. IMF has a much poorer prognosis and is associated with cytopenias,
      splenomegaly, extramedullary hematopoiesis, and bone marrow fibrosis.
      Stratification of risk for the development of complications from Ph-negative MPDs
      has guided the identification of appropriate therapies for this population.
      Intermediate/high-risk IMF or myelofibrosis after ET or PV is associated with a
      sufficiently poor prognosis to justify the use of allogeneic stem cell
      transplantation, which is capable of curing such patients. Reduced-intensity
      conditioning in preparation for allogeneic stem cell transplantation has
      permitted older patients with IMF to undergo transplantation with increasing
      success.

PMID- 17222786
TI  - Rb loss causes cancer by driving mitosis mad.
AB  - Aneuploidy is a hallmark of most human cancers, but whether it is a cause or a
      consequence of cellular transformation remains a subject of debate. The spindle
      checkpoint functions to prevent aneuploidy and plays a central role in this
      discussion. The checkpoint gene Mad2 is activated by E2F1 and overexpressed in
      cells lacking a functional Rb pathway. In this issue of Cancer Cell, Sotillo and
      coworkers report that Mad2 overexpression leads to chromosomal instability and
      tumorigenesis, indicating that Mad2 contributes to cancer development after Rb
      mutation. In a second paper, Weaver et al. report that aneuploidy has both tumor
      promoting and -suppressing properties.

PMID- 17222778
TI  - Reduced intensity conditioning for allogeneic hematopoietic cell transplantation:
      current perspectives.
AB  - Allogeneic HCT after myeloablative conditioning is an effective therapy for
      patients with hematologic malignancies. In an attempt to extend this therapy to
      older patients or those with comorbidities, reduced intensity or truly
      nonmyeloablative regimens have been developed over the past decade. The principle
      underlying reduced intensity regimens is to provide some tumor kill with lessened
      regimen-related morbidity and mortality and then rely on graft-versus-tumor (GVT)
      effects to eradicate remaining malignant cells, whereas nonmyeloablative regimens
      rely primarily on GVT effects. In this article, 3 representative approaches are
      described, demonstrating the clinical application for hematopoietic and
      nonhematopoietic malignancies. Current challenges include controlling GVHD while
      allowing GVT to occur. In the future, clinical trials using reduced intensity and
      nonmyeloablative conditioning will be compared with myeloablative conditioning in
      selected malignancies to extend the application to standard-risk patients.

PMID- 17222787
TI  - Hit 'em where they live: targeting the cancer stem cell niche.
AB  - Cancer stem cells (CSCs) are thought to be critical for initiation and
      propagation of many types of cancer. Because these cells are resistant to
      conventional therapies, they have been very difficult to eliminate. A study in
      this issue of Cancer Cell suggests that brain tumor CSCs live in a "vascular
      niche" that promotes their long-term growth and self-renewal. Disrupting this
      niche impairs CSC self-renewal and thereby significantly inhibits the growth of
      tumors. Targeting the unique microenvironment of CSCs may be the key to effective
      cancer therapy.

PMID- 17222788
TI  - Tracking normalization of brain tumor vasculature by magnetic imaging and
      proangiogenic biomarkers.
AB  - Clinical assessment of the response to antiangiogenic therapy has been
      cumbersome. A study in this issue of Cancer Cell demonstrates that a combination
      of magnetic resonance imaging (MRI) for quantification of normalized vessels with
      measurements of circulating levels of proangiogenic factors, including FGF2,
      SDF1, and viable circulating endothelial cells, provides an effective means to
      evaluate the response of recurrent glioblastoma to a prototypical pan-VEGF
      receptor tyrosine kinase inhibitor, AZD2171.

PMID- 17222789
TI  - A mitochondria-K+ channel axis is suppressed in cancer and its normalization
      promotes apoptosis and inhibits cancer growth.
AB  - The unique metabolic profile of cancer (aerobic glycolysis) might confer
      apoptosis resistance and be therapeutically targeted. Compared to normal cells,
      several human cancers have high mitochondrial membrane potential (DeltaPsim) and
      low expression of the K+ channel Kv1.5, both contributing to apoptosis
      resistance. Dichloroacetate (DCA) inhibits mitochondrial pyruvate dehydrogenase
      kinase (PDK), shifts metabolism from glycolysis to glucose oxidation, decreases
      DeltaPsim, increases mitochondrial H2O2, and activates Kv channels in all cancer,
      but not normal, cells; DCA upregulates Kv1.5 by an NFAT1-dependent mechanism. DCA
      induces apoptosis, decreases proliferation, and inhibits tumor growth, without
      apparent toxicity. Molecular inhibition of PDK2 by siRNA mimics DCA. The
      mitochondria-NFAT-Kv axis and PDK are important therapeutic targets in cancer;
      the orally available DCA is a promising selective anticancer agent.

PMID- 17222790
TI  - Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit
      tumor growth.
AB  - Neuropilin-1 (NRP1) guides the development of the nervous and vascular systems.
      Binding to either semaphorins or VEGF, NRP1 acts with plexins to regulate
      neuronal guidance, or with VEGFR2 to mediate vascular development. We have
      generated two monoclonal antibodies that bind to the Sema- and VEGF-binding
      domains of NRP1, respectively. Both antibodies reduce angiogenesis and vascular
      remodeling, while having little effect on other VEGFR2-mediated events.
      Importantly, anti-NRP1 antibodies have an additive effect with anti-VEGF therapy
      in reducing tumor growth. Vessels from tumors treated with anti-VEGF show a close
      association with pericytes, while tumors treated with both anti-NRP1 and anti
      VEGF lack this organization. We propose that blocking NRP1 function inhibits
      vascular remodeling, rendering vessels more susceptible to anti-VEGF therapy.

PMID- 17222791
TI  - A perivascular niche for brain tumor stem cells.
AB  - Cancers are believed to arise from cancer stem cells (CSCs), but it is not known
      if these cells remain dependent upon the niche microenvironments that regulate
      normal stem cells. We show that endothelial cells interact closely with self
      renewing brain tumor cells and secrete factors that maintain these cells in a
      stem cell-like state. Increasing the number of endothelial cells or blood vessels
      in orthotopic brain tumor xenografts expanded the fraction of self-renewing cells
      and accelerated the initiation and growth of tumors. Conversely, depletion of
      blood vessels from xenografts ablated self-renewing cells from tumors and
      arrested tumor growth. We propose that brain CSCs are maintained within vascular
      niches that are important targets for therapeutic approaches.

PMID- 17222793
TI  - Objective measurement of postocclusion surge during phacoemulsification in human
      eye-bank eyes.
AB  - PURPOSE: To objectively compare the postocclusion vacuum surge among different
      phacoemulsification machines and devices. DESIGN: Experimental study. METHODS:
      Infiniti, Legacy, Millennium, and Sovereign were tested in an eye-bank eye. All
      the machines were tested with 20-gauge non-ABS tips, 430 mm Hg vacuum pressure,
      24 ml/minute aspiration rate, peristaltic pump, and 75 cm bottle height. In
      addition, Infiniti and Legacy were also tested with 20-gauge bypass tips (ABS),
      125 cm bottle height, and 40 ml/minute flow rate. We also tested 19-gauge tips
      with Infiniti and Sovereign and the venturi pump for Millennium. RESULTS:
      Significant differences were found between all the machines tested with
      Millennium peristaltic generating the least and Millennium Venturi the most
      surge. ABS tips significantly decreased the surge for Legacy but not for
      Infiniti. Cruise Control (CC) had a significant effect on Sovereign but not on
      Millennium. Increasing the bottle height decreased surge while increasing the
      flow increased surge for both Infiniti and Legacy. The 19-gauge tips increased
      surge for both Infiniti and Sovereign. CONCLUSIONS: Surge varied over a range of
      40 microm to more than 2 mm. ABS and CC decrease surge, especially when the
      machine is not functioning near the limits of surge prevention. Certain
      parameters, such as a 19-gauge tip and high flow, dramatically increased surge,
      whereas elevating the bottle ameliorates it. Understanding the impact of all
      these features will help in minimizing the problem.

PMID- 17222792
TI  - AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor
      vasculature and alleviates edema in glioblastoma patients.
AB  - Using MRI techniques, we show here that normalization of tumor vessels in
      recurrent glioblastoma patients by daily administration of AZD2171-an oral
      tyrosine kinase inhibitor of VEGF receptors-has rapid onset, is prolonged but
      reversible, and has the significant clinical benefit of alleviating edema.
      Reversal of normalization began by 28 days, though some features persisted for as
      long as four months. Basic FGF, SDF1alpha, and viable circulating endothelial
      cells (CECs) increased when tumors escaped treatment, and circulating progenitor
      cells (CPCs) increased when tumors progressed after drug interruption. Our study
      provides insight into different mechanisms of action of this class of drugs in
      recurrent glioblastoma patients and suggests that the timing of combination
      therapy may be critical for optimizing activity against this tumor.

PMID- 17222794
TI  - Central toxic keratopathy: description of a syndrome in laser refractive surgery.
AB  - PURPOSE: To describe the clinical spectrum of a syndrome in laser refractive
      surgery, which we call central toxic keratopathy, and to present cases that
      illustrate the range of this syndrome. DESIGN: Retrospective observational case
      series. METHODS: Eyes with noninflammatory central corneal opacification in the
      immediate postoperative period after photorefractive keratectomy (PRK) or laser
      in situ keratomileusis (LASIK) were identified, and the charts abstracted.
      RESULTS: Twenty-three eyes of 14 patients were identified who developed central
      corneal opacification three to nine days after laser refractive surgery. Nineteen
      of these eyes had LASIK and four had PRK. All eyes had central corneal
      opacification in the area of laser treatment that extended posteriorly from the
      interface into the stromal bed (in the case of LASIK eyes). The opacification
      persisted a minimum of two months to a maximum of 18 months before clearing. Nine
      eyes developed postoperative hyperopia of greater than 2 diopters. Pre- and
      postoperative best-spectacle corrected acuity was available on 19 eyes; one of
      these eyes lost two lines of corrected acuity, and two other eyes lost one line.
      Eighteen of 19 LASIK eyes had diffuse lamellar keratitis preceding the onset of
      corneal opacification. CONCLUSIONS: Central toxic keratopathy is characterized by
      noninflammatory central corneal opacification with a significant hyperopic shift.
      The opacification gradually clears over a period of months, leaving the eye
      hyperopic. Enhancement is indicated to treat residual hyperopia and remove
      residual striae. Topical or oral corticosteroid treatment is not indicated. The
      cause of central toxic keratopathy is unknown.

PMID- 17222795
TI  - Real-time quantification of RNA polymerase activity using a "broken beacon".
AB  - A novel assay using a hybridization-based method was developed for real-time
      monitoring of RNA synthesis. In this work, a "broken beacon" in which the fluor
      and quencher were located on separate but complementary oligonucleotides was used
      to quantify the amount of RNA production by T7 polymerase. The relative lengths
      of the fluor-oligo and quencher-oligo, and their relative concentrations were
      optimized. The experimentally determined limit-of-detection was approximately 45
      nM. The new assay was compared to the "gold-standard" radiolabel ([(32)P]NTP
      incorporation) assay for RNA quantification. While the broken beacon assay
      exhibited a higher limit of detection, it provided an accurate measure of RNA
      production rates. However, the broken beacon assay provided the significant
      analytical advantages of (i) a real-time and continuous measurement, (ii) no
      requirement for the use of radiolabels or gel-based analysis, and (iii)
      substantial time and labor savings.

PMID- 17222796
TI  - The role of periodontal mechanoreceptors in mastication.
AB  - The aim of this review is to discuss what is known about the reflex control of
      the human masticatory system by the periodontal mechanoreceptors and to put
      forward a method for standardised investigation. To deliver mechanical stimulus
      in a reproducible way, the following precautions are suggested: the stimulus
      should be brought into secure contact with the area of stimulation, and slack
      between the probe and the area to be stimulated should be taken up by the
      application of a preload. It is also important to ensure that there is minimal
      simultaneous activation of receptor systems other than the periodontal
      mechanoreceptors. It is also necessary to standardise the method for recording
      and analysing the response.

PMID- 17222797
TI  - Small heat shock protein alphaB-crystallin binds to p53 to sequester its
      translocation to mitochondria during hydrogen peroxide-induced apoptosis.
AB  - Apoptosis is a highly conserved procedure of cell death and occurs under various
      stimuli, including oxidative stress. A small heat shock protein, alphaB
      crystallin, is found to process resistance to apoptosis in some cells and
      tissues. But the mechanisms under this protective role are not fully understood.
      In the present study, we reported the early protective role of alphaB-crystallin
      against hydrogen peroxide-induced apoptosis in mice myogenic C(2)C(12) cells.
      alphaB-Crystallin interacted with p53, a proapoptotic protein, during cell
      apoptosis and such protein interaction mainly occurred in the cytoplasm of the
      cells, suggesting that the interaction of alphaB-crystallin with p53 might
      prevent the translocation of p53 from cytoplasm to mitochondria. Hence, this
      study provides a hint that alphaB-crystallin affects on p53 mitochondrial
      translocation during oxidative stress-induced apoptosis.

PMID- 17222798
TI  - RRM2 induces NF-kappaB-dependent MMP-9 activation and enhances cellular
      invasiveness.
AB  - Ribonucleotide reductase is a dimeric enzyme that catalyzes conversion of
      ribonucleotide 5'-diphosphates to their 2'-deoxynucleotide forms, a rate-limiting
      step in the production of 2'-deoxyribonucleoside 5'-triphosphates required for
      DNA synthesis. The ribonucleotide reductase M2 subunit (RRM2) is a determinant of
      malignant cellular behavior in a range of human cancers. We examined the effect
      of RRM2 overexpression on pancreatic adenocarcinoma cellular invasiveness and
      nuclear factor-kappaB (NF-kappaB) transcription factor activity. RRM2
      overexpression increases pancreatic adenocarcinoma cellular invasiveness and MMP
      9 expression in a NF-kappaB-dependent manner. RNA interference (RNAi)-mediated
      silencing of RRM2 expression attenuates cellular invasiveness and NF-kappaB
      activity. NF-kappaB is a key mediator of the invasive phenotypic changes induced
      by RRM2 overexpression.

PMID- 17222799
TI  - Intermolecular relations between the glucocorticoid receptor, ZAP-70 kinase, and
      Hsp-90.
AB  - The glucocorticoid receptor (GR) participates in both genomic and non-genomic
      glucocorticoid hormone (GC) actions by interacting with other cytoplasmic
      signalling proteins. Previously, we have shown that high dose Dexamethasone (DX)
      treatment of Jurkat cells causes tyrosine phosphorylation of ZAP-70 within 5 min
      in a GR-dependent manner. By using co-immunoprecipitation and confocal
      microscopy, here we demonstrate that the liganded GR physically associates with
      ZAP-70, in addition to its phosphorylation changes. The association of the ligand
      bound GR and ZAP-70 was also observed in HeLa cells transfected with ZAP-70,
      suggesting that this co-clustering is independent of lymphocyte specific factors.
      Furthermore, the ZAP-70 was found to also co-precipitate with Hsp-90 chaperone
      both in Jurkat and transgenic HeLa cells, independent of the presence of DX.
      These findings raise the possibility that ZAP-70 may serve as an important link
      between GC and TcR-induced signaling, thereby transmitting non-genomic GC action
      in T-cells.

PMID- 17222800
TI  - Characterization and functional analysis of a novel double-guide C/D box snoRNA
      in the fission yeast.
AB  - Ribose methylation of eukaryotic rRNA is directed by box C/D small nucleolar RNAs
      (snoRNAs), which pinpoint the nucleotide to be methylated in specific position
      within the rRNA sequence. Here, we report the identification of a novel double
      guide C/D box snoRNA termed snR88 that directs methylation of two previously
      undetermined sites in 25S rRNA from the fission yeast. Knockout of the predicted
      TATA box of the snR88 gene resulted in the complete blocking of its expression,
      showing that snR88 is an independently transcribed gene and dispensable for yeast
      viability. The depletion of snR88 abolished 25S rRNA methylation at U2304 and
      U2497 simultaneously. Interestingly, an unusual pause of reverse transcription at
      U2495 was observed, which implies an unknown structure of 25S rRNA related to
      ribose methylation at U2497 in the fission yeast.

PMID- 17222801
TI  - Wnt/beta-catenin signaling regulates expression of PRDC, an antagonist of the BMP
      4 signaling pathway.
AB  - To identify novel target genes regulated by Wnt/beta-catenin signaling,
      microarray analysis was performed with L929 fibroblast cells. In this report, we
      show that the expression of PRDC (Protein Related to DAN and Cerberus),
      previously known as an antagonist of Nodal, BMP (bone morphogenetic protein), and
      Wnt signals, is specifically induced by Wnt/beta-catenin signaling, and also show
      that the transcriptional activation is mediated in a Tcf/LEF-independent manner.
      The PRDC induced by Wnt/beta-catenin does not inhibit Wnt signaling, but does
      inhibit BMP-4 signaling. The inhibition of BMP-4-induced reporter activity by the
      treatment of conditioned media from beta-catenin(S37A)-expressing cells suggests
      that the PRDC induced by beta-catenin is secreted outside of cells and
      antagonizes BMP-4 signaling. We propose that PRDC might serve as a mediator to
      antagonize BMP-4 signaling by Wnt.

PMID- 17222802
TI  - Enhanced ceramide-induced apoptosis in ceramide kinase overexpressing cells.
AB  - We evaluated how increased levels of ceramide kinase (CerK) would impact the
      growth of COS-1 fibroblasts and RBL-2H3 basophils. The low CerK activity in these
      cells was strongly up-regulated upon recombinant expression of CerK. CerK
      overexpressing COS-1 cells depended on higher concentrations of serum for their
      growth and displayed many filipodia. The two CerK-overexpressing cell lines were
      more sensitive to C2-ceramide-mediated apoptosis, and this correlated with the
      production of C2-ceramide-1-phosphate by CerK. This study indicates that ceramide
      kinase may participate in the control of cell growth, and establishes a novel
      assay that will be valuable for testing ceramide kinase inhibitors.

PMID- 17222803
TI  - Negative regulation of ISG15 E3 ligase EFP through its autoISGylation.
AB  - The function of ubiquitin-like protein ISG15 and protein modification by ISG15
      (ISGylation) has been an enigma for many years. Recently, the research of
      ISGylation has been accelerated by the identification of the enzymes involved in
      the ISG15 conjugation process. Our previous study identified the interferon
      inducible protein EFP as an ISG15 isopeptide ligase (E3) for 14-3-3sigma. In this
      study, we show that ISG15 E3 ligase EFP can be modified by ISG15. Two ubiquitin
      E2 conjugating enzymes, UbcH6 and UbcH8, can support ISGylation of EFP. The Ring
      finger domain of EFP is important for its ISGylation. Full-length EFP can enhance
      the ISGylation of Ring domain deleted EFP, indicating EFP can function as an
      ISG15 E3 ligase for itself. We also determined the ISGylation site of EFP and
      created its ISGylation resistant mutant EFP-K117R. Compared to the wild-type EFP,
      this mutant further increases the ISGylation of 14-3-3sigma. Thus we propose that
      autoISGylation of EFP negatively regulates its ISG15 E3 ligase activity for 14-3
      3sigma.

PMID- 17222804
TI  - The N-terminal of a heparin-binding sperm membrane mitogen possess lectin-like
      sequence.
AB  - Glycosaminoglycans like heparin and heparin sulfate in follicular fluid induce
      changes in the intracellular environment during the spermatozoal functional
      maturation. We previously reported the isolation, purification and partial
      characterization of a heparin binding sperm membrane protein (HBSM). In the
      present study, the amino acids analysis provided evidence of a single sequence,
      which suggest the homogeneity of the purified HBSM. Fourteen amino acids--(1)A D
      T I V A V E L D T Y P N(14)--correspond to the amino terminal sequence of
      Concanavalin A (Con A) and contain 45.2% carbohydrate by weight. HBSM possess
      mitogenic property on lymphocytes with comparable magnitude to the well-known
      mitogen; Con A, inducing 83% radiolabel thymidine incorporation in growing
      lymphocytes. Unlike Con A, there was no agglutination of cell by HBSM upto 5
      ng/ml concentration. Interestingly, we found that heparin and chondroitin sulfate
      conjugated HBSM inhibit the proliferative activity. Similar effect was also found
      with an in-house isolate sulfated glycans; G-I (28% sulfate). In contrast, there
      was no inhibition by the desulfated form; G-ID. Altogether, our data suggest that
      the mechanism of cell proliferative pathway may be different for HBSM and Con A.

PMID- 17222805
TI  - Antimicrobial properties of derivatives of the cationic tryptophan-rich
      hexapeptide PAF26.
AB  - Short antimicrobial peptides represent an alternative to fight pathogen
      infections. PAF26 is a hexapeptide identified previously by a combinatorial
      approach against the fungus Penicillium digitatum and shows antimicrobial
      properties towards certain phytopathogenic fungi. In this work, PAF26 was used as
      lead compound and its properties were compared with two series of derivatives,
      obtained by either systematic alanine substitution or N-terminal amino acid
      addition. The alanine scan approach underlined the optimized sequence of PAF26 in
      terms of potency and permeation capability, and also the higher contribution of
      the cationic residues to these properties. The N-terminal addition of amino acids
      resulted in new heptapeptides with variations in their antimicrobial
      characteristics, and very low cytolysis to human red blood cells. Positive (Arg
      or Lys) and aromatic (Phe or Trp) residue addition increased broad spectrum
      activity of PAF26. Noteworthy, addition of selected residues had specific effects
      on the properties of derivatives of PAF26.

PMID- 17222806
TI  - Antipsychotics inhibit TREK but not TRAAK channels.
AB  - Schizophrenia is a chronic mental illness affecting 0.4% of the population.
      Existing antipsychotic drugs are mainly used to treat positive symptoms such as
      hallucinations but have only poor effects on negative symptoms such as cognitive
      deficits or depression. TREK and TRAAK channels are two P domain background
      potassium channels activated by polyunsaturated fatty acids and mechanical
      stress. TREK but not TRAAK channels are regulated by Gs- and Gq-coupled pathways.
      The inactivation of the TREK-1 but not the TRAAK channel in mice results in a
      depression-resistant phenotype. In addition, it has been shown that
      antidepressants such as fluoxetine or paroxetine directly inhibit TREK channel
      activity. Here we show that different antipsychotic drugs directly inhibit TREK
      currents with IC(50) values of approximately 1 to approximately 20 microM. No
      effect is seen on TRAAK channel activity. We conclude that TREK channels might be
      involved in the therapeutic action of antipsychotics or in their secondary
      effects. Furthermore, TREK channels could play a role in the pathophysiology of
      psychiatric disorders such as depression and schizophrenia.

PMID- 17222807
TI  - S100A9 mediates neutrophil adhesion to fibronectin through activation of beta2
      integrins.
AB  - Neutrophil migration from the blood to inflammatory sites follows a cascade of
      events, in which adhesion to endothelial cells and extracellular matrix proteins
      is essential. S100A8, S100A9, and S100A12 are small abundant proteins found in
      human neutrophil cytosol and presumed to be involved in leukocyte migration. Here
      we investigated the S100 proteins' activities in neutrophil tissue migration by
      evaluating their effects on neutrophil adhesion to certain extracellular matrix
      proteins. S100A9 induced adhesion only to fibronectin and was the only S100
      protein that stimulated neutrophil adhesion to this extracellular matrix protein.
      Experiments with blocking antibodies revealed that neither beta1 nor beta3
      integrins were strongly involved in neutrophil adhesion to fibronectin, contrary
      to what the literature predicted. In contrast, neutrophil adhesion to fibronectin
      was completely inhibited by anti-beta2 integrins, suggesting that S100A9-induced
      specific activation of beta2 integrin is essential to neutrophil adhesion.

PMID- 17222808
TI  - Matrix metalloproteinase-7-catalyzed release of HB-EGF mediates
      deoxycholyltaurine-induced proliferation of a human colon cancer cell line.
AB  - Prior evidence indicates that bile acids stimulate colon cancer cell
      proliferation by muscarinic receptor-induced transactivation of epidermal growth
      factor receptors (EGFR). To explore further the mechanism underlying this action,
      we tested the hypothesis that bile acids activate a matrix metalloproteinase
      (MMP) that catalyzes release of an EGFR ligand. Initial studies showed that non
      selective MMP inhibitors blocked the actions of deoxycholyltaurine (DCT), thereby
      indicating a role for MMP-catalyzed release of an EGFR ligand. DCT-induced cell
      proliferation was reduced by increasing concentrations of EGFR kinase inhibitors,
      by antibodies to the ligand binding domain of EGFR, by neutralizing antibodies to
      heparin binding-EGF-like growth factor (HB-EGF) and by CRM197, an inhibitor of HB
      EGF release. These findings and our observations with more selective MMP
      inhibitors suggested that MMP-7, an enzyme known to release HB-EGF, plays a key
      role in mediating bile acid-induced H508 colon cancer cell proliferation. We
      observed that recombinant HB-EGF and MMP-7 mimicked both the signaling and
      proliferative actions of bile acids. Strikingly, reducing MMP-7 expression with
      either neutralizing antibody or small interfering RNA attenuated the actions of
      DCT. MMP-7 expression in H508 cells was confirmed using quantitative reverse
      transcription PCR. DCT stimulated a greater than 10-fold increase in MMP-7 gene
      transcription. Co-localization of pro-MMP-7 and pro-HB-EGF at the cell surface
      (immunofluorescence microscopy) was demonstrated, indicating proximity of the
      enzyme to its substrate. These findings provide strong evidence that in H508
      human colon cancer cells, DCT-induced transactivation of EGFR is mediated by MMP
      7-catalyzed release of the EGFR ligand HB-EGF.

PMID- 17222809
TI  - Organisation of the mouse sinoatrial node: structure and expression of HCN
      channels.
AB  - OBJECTIVE: To reveal the structural characteristics of the sinoatrial node (SAN)
      and the distribution of hyperpolarization-activated cyclic nucleotide-gated
      cation channels (HCN) in the SAN in the mouse. METHODS: The structure of the SAN
      and the distribution of HCN channels in the SAN in the mouse were studied by
      histology and immunolabelling of ANP, Cx43 and HCN channels. RESULTS: The mouse
      SAN is a comma-shaped structure with a length of approximately 1.5 mm parallel to
      the crista terminalis and is separated from atrial muscle by connective tissue at
      the border both with the crista terminalis and the atrial septum. A unique
      compact nodal structure with densely-packed nodal cells was identified at the
      head of the comma-shaped SAN. Cell size and fibre orientation vary regionally in
      the SAN: the cells in the compact node are small and are orientated perpendicular
      to the crista terminalis, whereas the cells in the more inferior part are larger
      and more loosely-packed and are orientated parallel to the crista terminalis. All
      SAN cells exhibited labelling of HCN4, but no cell exhibited detectable labelling
      of HCN1, HCN2, ANP and Cx43, while surrounding atrial cells exhibited labelling
      of ANP and Cx43, but not HCN1, HCN2 and HCN4. A specialised interface between the
      SAN and surrounding atrial muscle was also identified: strands of HCN4-positive
      nodal cells protrude into the atrial muscle and strands of Cx43-positive atrial
      cells protrude into the SAN; thus, there are interdigitations between the SAN and
      atrial muscle. CONCLUSIONS: In the mouse, (i) the SAN is structurally complex
      with a densely-packed head and loosely-packed tail; (ii) HCN4 is the only HCN
      isoform detectable and is present throughout the SAN; and (iii) there is a
      specialised interface between the SAN and surrounding atrium that may be
      necessary for the SAN to drive the more hyperpolarized atrial muscle.

PMID- 17222810
TI  - Ca2+/calmodulin-dependent protein kinase: a key component in the contractile
      recovery from acidosis.
AB  - Intracellular acidosis exerts substantial effects on the contractile performance
      of the heart. Soon after the onset of acidosis, contractility diminishes, largely
      due to a decrease in myofilament Ca(2+) responsiveness. This decrease in
      contractility is followed by a progressive recovery that occurs despite the
      persistent acidosis. This recovery is the result of different mechanisms that
      converge to increase diastolic Ca(2+) levels and Ca(2+) transient amplitude.
      Recent experimental evidence indicates that activation of the Ca(2+)/calmodulin
      dependent protein kinase II (CaMKII) is an essential step in the sequence of
      events that increases the Ca(2+) transient amplitude and produces contractile
      recovery. CaMKII may act as an amplifier, providing compensatory pathways to
      offset the inhibitory effects of acidosis on many of the Ca(2+) handling
      proteins. CaMKII-induced phosphorylation of the SERCA2a regulatory protein
      phospholamban (PLN) has the potential to promote an increase in sarcoplasmic
      reticulum (SR) Ca(2+) uptake and SR Ca(2+) load, and is a likely candidate to
      mediate the mechanical recovery from acidosis. In addition, CaMKII-dependent
      phosphorylation of proteins other than PLN may also contribute to this recovery.

PMID- 17222811
TI  - The influence of estimated creatinine clearance on plasma homocysteine in
      hypertensive patients with normal serum creatinine.
AB  - OBJECTIVES: To examine the relation of estimated creatinine clearance (eCrCl) and
      plasma total homocysteine (tHcy) in hypertensive patients with a normal serum
      creatinine level. DESIGN AND METHODS: A total of 137 hypertensive patients (mean
      age 66.6 years, 69 men) with serum creatinine level </=1.5 mg/dL gave 10-h
      fasting blood samples for measurement of tHcy, serum folic acid, and serum
      vitamin B(12). RESULTS: 95 patients fell into a chronic renal insufficiency (CRI)
      group (eCrCl< or =60 mL/min/1.73 m(2)) and 42 into a normal renal function (NRF)
      group (eCrCl>60 mL/min/1.73 m(2)). The CRI group was older (p<0.001), had higher
      tHcy (p<0.001), higher serum urea nitrogen (p<0.001), higher serum creatinine
      (p<0.001), lower eCrCl (p<0.001), and lower diastolic blood pressure (p=0.001).
      In univariate analysis, eCrCl had the strongest correlation with tHcy (r=-0.453,
      p<0.001). Significant correlations, ranging in decreasing order from r=-0.418,
      p<0.001 to r=-0.170, p=0.047, were also noted between tHcy and twelve other
      variables. In multivariate analysis, only eCrCl (p<0.001), usage of fibrate
      (p<0.001), serum level of vitamin B(12) (p=0.002), serum level of folic acid
      (p=0.009), and smoking (p=0.027) were independent predictors of tHcy. CONCLUSION:
      eCrCl is a strong independent predictor of tHcy in hypertensive patients with
      normal serum creatinine.

PMID- 17222812
TI  - Clinical efficacy and cost-effectiveness of newborn screening for medium chain
      acyl-CoA dehydrogenase deficiency using tandem mass spectrometry.
AB  - OBJECTIVE: To determine the clinical efficacy and cost-effectiveness of newborn
      screening for MCADD using tandem mass spectrometry (MS/MS) compared with clinical
      diagnosis within the Canadian context. DESIGN AND METHODS: A systematic review of
      the clinical and economic literature was performed. For primary economic
      analysis, a decision-tree model was built based on the available information, the
      impact of newborn screening on the health care and the relevant Canadian data.
      RESULTS: Twenty-one clinical and two economic studies met the selection criteria.
      Mean incidence of MCADD was approximately 1:16,000. Clinical sensitivity and
      specificity were 100% and 99.99%, respectively. Screening significantly lowered
      morbidity and mortality. Both economic studies showed that screening for MCADD
      using MS/MS was cost-effective if willingness-to-pay was US 50,000 dollars. Our
      primary economic analysis showed that screening was cost-effective based on the
      cost-effective threshold of C 20,000 dollars per QALY. CONCLUSION: Screening
      consumes more resources than no screening but attains better health outcomes.

PMID- 17222813
TI  - Enalapril and losartan affect lipid peroxidation in renal transplant recipients
      with renin-angiotensin system polymorphisms.
AB  - OBJECTIVES: In this study, the effect of enalapril (E) and/or losartan (L) on
      lipid peroxidation (LPO) is studied in renal transplant recipients (RTRs) with
      regard to polymorphisms of renin-angiotensin system (RAS). DESIGN AND METHODS:
      After determination of genotypes of the angiotensin-converting enzyme (ACE I/D),
      angiotensinogen (AGT M235T) and angiotensin II type 1 receptor (ATR1 A1166C) by
      PCR, sixty-four RTRs recruited to four groups randomly: first (13 patients) and
      second (20 patients) groups were treated with enalapril (E(+): 10 mg/day) and
      losartan (L(+): 50 mg/day) alone for 2 months, respectively. After 2 weeks as
      washout period, E group changed to L and vice versa as a cross-over design and
      they were treated for another 2 months. The third group (13 patients) as positive
      control received enalapril+losartan (E(+)L(+): 10 mg/day+50 mg/day) for 16 weeks,
      and the forth group (18 patients) as negative control received no medication (E(
      )L(-)). Malondialdehyde (MDA) as LPO marker was measured before and after
      treatment. In this study, P<0.05 was considered significant. RESULTS: After 2
      months of treatment, MDA level significantly decreased in all of the groups
      except the E(-)L(-). MDA level in pre- vs. post-intervention for the E(+)L(+),
      E(+), L(+) and E(-)L(-) groups were as follows: 5.81+/-2.13 nmol/mL vs. 1.61+/
      0.80 nmol/mL (P=0.001), 5.10+/-2.05 nmol/mL vs. 1.68+/-1.01 nmol/mL (P=0.003),
      5.20+/-1.61 nmol/mL vs. 1.22+/-0.27 nmol/mL (P=0.000) and 5.27+/-2.12 nmol/mL vs.
      5.07+/-2.03 nmol/mL (P=0.52), respectively. Also, the same results were found in
      the end of 16th week. Although patients with DD genotype of ACE had higher MDA
      (P=0.01) levels, RAS polymorphisms could not predict the antioxidative response
      rate to the drugs (P>0.05). CONCLUSIONS: E and/or L reduce MDA regardless of the
      RAS genotypes.

PMID- 17222814
TI  - A note on the use of outlier criteria in Ontario laboratory quality control
      schemes.
AB  - OBJECTIVES: This paper examines the pitfalls that arise when an outlier is
      assessed using a criterion based on a fixed multiple of the standard deviation
      rather than an established statistical test. Although the former approach is
      statistically invalid, it is the favored method for identifying outliers in
      Ontario laboratory quality control protocols. DESIGN AND METHODS: Computer
      simulations are used to calculate the probability of a false positive result
      (classifying a valid observation as an outlier) when outlier criteria based on
      fixed multiples of the standard deviation are applied to samples containing no
      outliers. RESULTS: The estimated probability of a false positive result is
      tabulated over various sample sizes. Outlier criteria based on fixed multiples of
      the standard deviation are shown to be highly inefficient. CONCLUSIONS: This work
      presents arguments for discontinuing the widespread practice of using outlier
      criteria based on fixed multiples of the standard deviation to identify outliers
      in univariate samples.

PMID- 17222815
TI  - Effect of waist circumference on reference intervals of liver-related enzyme
      tests in apparently healthy adult Mexican Americans, black and white Americans.
AB  - BACKGROUND: We used a more comprehensible and more physiologically valid
      indicator of obesity-related liver disease, waist circumference (WC), rather than
      BMI to study the effect of obesity on liver enzymes, easily measurable surrogates
      of liver disease. METHODS: WC, liver enzymes and pertinent demographic data were
      abstracted from NHANES III. After exclusion criteria were applied, we stratified
      the populations by sex and ethnicity and graphed the percentage of elevated
      enzymes per WC interval. RESULTS: There was a significant relationship between
      enzyme activity and WC (p<0.001 for ALT, p<0.01 for ALP, p<0.01 for AST, p=0.02
      for GGT and p<0.05 for LD), and the relationship was stronger in females
      (p<0.002) and Mexican Americans (p<0.001). The enzyme-WC relationship is much
      weaker in non-Hispanic black females and males. CONCLUSION: As increases in liver
      enzyme activity can indicate potentially reversible liver disease, our graphs
      should be used by physicians to motivate obese, apparently healthy Mexican
      American and non-Hispanic white patients with elevated liver enzymes to reduce
      their WC.

PMID- 17222816
TI  - Algorithms and heuristics for efficient medical information display in PDA.
AB  - Accessing medical information in mobile devices such as PDAs and mobile phones is
      becoming widespread. Since these devices do not have the same rendering
      capabilities as of desktop computers, it is necessary for medical information to
      be fragmented for proper presentation on these types of devices. In this paper,
      we propose an architecture for displaying medical information in PDA. In the
      proposed system, a server extracts the information, categorizes the information
      in order of its relevance for diagnosis, and dynamically generates a hierarchical
      view of the relevant information based on certain medical domain knowledge.
      Displaying image and graphics data in PDA poses several challenges. The proposed
      system supports an image visualization tool, which interactively displays an
      image or a portion of an image in user's PDA. This visualization tools increases
      the resource utilization of PDA by offloading a part of the computation to the
      server. A suitable caching scheme is incorporated for optimum utilization of
      communication channel bandwidth.

PMID- 17222817
TI  - N-cadherin mediates cortical organization in the mouse brain.
AB  - The cerebral cortex is a complex laminated structure generated by the sequential
      migration of developing neurons from the ventricular zone. One of the molecules
      that may play a role in cortical morphogenesis is N-cadherin since its blocking
      causes disruption of the ordered arrangement of cells in other neural tissues,
      such as the neural retina. Here, we show that when the N-cadherin gene had been
      conditionally deleted in the mouse cerebral cortex, the intra-cortical structures
      were nearly completely randomized; e.g., mitotic cells and postmitotic cells were
      scattered throughout the cortex without any order. These defects seemed to mainly
      originate from the disruption of the adherens junctions (AJs) localized in the
      apical end of neuroepithelial cells, where N-cadherin is normally most highly
      concentrated. In the absence of N-cadherin, neuroepithelial or radial glial cells
      could not expand their bodies or processes to span the distance between the
      ventricular and pial surfaces and therefore terminated them in the middle zone of
      the cortex. These results demonstrate that N-cadherin is essential for
      maintaining the normal architecture of neuroepithelial or radial glial cells and
      that their disruption randomizes the internal structures of the cortex.

PMID- 17222818
TI  - Epibranchial and otic placodes are induced by a common Fgf signal, but their
      subsequent development is independent.
AB  - The epibranchial placodes are cranial, ectodermal thickenings that give rise to
      sensory neurons of the peripheral nervous system. Despite their importance in the
      developing animal, the signals responsible for their induction remain unknown.
      Using the placodal marker, sox3, we have shown that the same Fgf signaling
      required for otic vesicle development is required for the development of the
      epibranchial placodes. Loss of both Fgf3 and Fgf8 is sufficient to block placode
      development. We further show that epibranchial sox3 expression is unaffected in
      mutants in which no otic placode forms, where dlx3b and dlx4b are knocked down,
      or deleted along with sox9a. However, the forkhead factor, Foxi1, is required for
      both otic and epibranchial placode development. Thus, both the otic and
      epibranchial placodes form in a common region of ectoderm under the influence of
      Fgfs, but these two structures subsequently develop independently. Although
      previous studies have investigated the signals that trigger neurogenesis from the
      epibranchial placodes, this represents the first demonstration of the signaling
      events that underlie the formation of the placodes themselves, and therefore, the
      process that determines which ectodermal cells will adopt a neural fate.

PMID- 17222819
TI  - Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on,
      Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice.
AB  - We examined whether treatment with amodiaquine, a potent inhibitor of histamine N
      methyltransferase protects mice from Propionibacterium acnes (P. acnes)-primed
      and lipopolysaccharide (LPS)-induced hepatitis. The subcutaneous injection of
      amodiaquine (2 and 5 mg/kg) significantly increased the histamine levels in the
      liver in comparison to saline treated mice. Pretreatment with amodiaquine also
      improved the survival rate of the hepatitis mice, and this improvement was
      partially associated with the decrease in serum levels of aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT). Amodiaquine partially
      suppressed increases of tumor necrosis factor (TNF)-alpha in the serum and TNF
      alpha mRNA expression in the liver, whereas the expression of interleukin (IL)
      18, interferon (IFN)-gamma and IL-12 in the liver was not changed by amodiaquine
      treatment. In conclusion, the present findings suggested that the elevation of
      endogenous histamine by amodiaquine may thus play a protective role through the
      regulation of TNF-alpha production in endotoxin-induced hepatic injury mice.

PMID- 17222820
TI  - Accumulation of immune cells and high expression of chemokines/chemokine
      receptors in the upstream shoulder of atherosclerotic carotid plaques.
AB  - The presence of immune cells is important for plaque destabilization. Disturbed
      flow conditions were shown to enhance the recruitment of circulating immune
      cells. Thus, we analyzed in 54 atherosclerotic carotid plaques the frequency of
      different immune cells, HLA-DR, chemokines, and chemokine receptors, comparing
      the upstream with the downstream plaque shoulder. The presence of
      neovascularization and intraplaque hemorrhages was investigated by CD34
      immunostaining and Mallory's iron stain. Immunohistochemical analyses were
      performed to detect smooth muscle cells (SMC: actin), macrophages (CD68), T cells
      (CD3), dendritic cells (DC: fascin), mature DC (CD83), and the expression of HLA
      DR, chemokine receptors (CCR-2, CCR-6), and chemokines (MCP-1, MIP-3alpha).
      Significantly more SMC were detected downstream than upstream (p<0.001). In
      contrast, significantly more macrophages (p=0.01), DC (p=0.03), mature DC
      (p=0.007), and a higher expression of HLA-DR (p=0.004), CCR-2 (p=0.002), CCR-6
      (p<0.001), MCP-1 (p=0.04), and MIP-3alpha (p=NS) were observed upstream than
      downstream. Immune cells were strongly associated with neovascularization. The
      abundance of SMC downstream provides an explanation for distal plaque growth.
      Enhanced recruitment of immune cells through neovessels into the upstream
      shoulder might be contributing to plaque destabilization.

PMID- 17222821
TI  - Development of a novel quantitative real-time assay using duplex scorpion primer
      for detection of Chlamydia trachomatis.
AB  - A novel quantitative real-time PCR method using the duplex scorpion primer for
      detection of Chlamydia trachomatis DNA was developed and validated. The assay
      employs a duplex primer; its most important feature is the intramolecular probe
      target interaction. The assay had many prominent characteristics. (i) The duplex
      probe is simpler to synthesize and significantly easier to purify than TaqMan
      probe because that the fluorescent dye pair and the quencher pair are in
      different oligonucleotides. (ii) The method has high sensitivity, specificity,
      intra- and interassay reproducibilities. (iii) The assay has a quantitative
      dynamic range of 25 to10(9) genome copies per reaction mixture. (iv) The scorpion
      system can identify 98.6% samples in the validation panel without retest. There
      were 81 positive samples and 67 negative samples, which were confirmed by two FDA
      approved NAATs (the Roche Amplicor PCR assay, Abbott LCR kit) and our new method.
      Any two positive results out of the possible three-comparator results would
      define the infected-patient gold standard. Of the positive samples, 79 (97.5%)
      were found positive (ranging from 31 to 227,648 copies/microl, M=4219
      copies/microl), whereas no negative samples were found positive by the assay. A
      quantitative, fast, and easy-to-handle diagnostic approach such as the MOMP-based
      real-time PCR described here might improve the detection of C. trachomatis
      infection.

PMID- 17222822
TI  - Role of interleukin-6 in a glucan-induced model of granulomatous vasculitis.
AB  - The role of interleukin-6 (IL-6) in granulomatous vasculitis is not well
      understood. To investigate its involvement in this type of vasculitis a model of
      glucan-induced pulmonary vasculitis employed interleukin-6 deficient (IL-6-/-)
      mice. Briefly, IL-6-/- mice and C57B/J6 wild type (IL-6+/+) mice were injected
      intravenously with a suspension of glucan isolated from the cell wall of bakers
      yeast which results in a granulomatous vasculitis primarily in the pulmonary
      vasculature. Histological examination demonstrated no significant difference in
      the number of infiltrating leukocytes between the IL-6+/+ and IL-6-/- glucan
      injured mice. Similar numbers of granulomas were noted in both the IL-6+/+ and IL
      6-/- injured animals, while no granulomas were seen in saline injected control
      mice. Cells recovered from the bronchoalveolar lavage (BAL) fluid were
      differentially stained and counted. While there was a significant increase in
      infiltrating leukocytes recovered from the BAL following glucan-induced injury,
      there was no significant difference between the IL-6+/+ and IL-6-/- mice. In
      addition, no difference was demonstrated in total protein content in the BAL
      fluid between IL-6+/+ and IL-6-/- mice. However, myeloperoxidase (MPO) activity
      in the lungs of the IL-6-/- mice was less than in their IL-6+/+ counterparts
      suggesting that these animals have a partial defect in their ability to recruit
      neutrophils in this model. Studies done to look for levels of other
      cytokines/chemokines in these animals to compensate for the loss of IL-6 revealed
      that only IL-10 in the sera (p<0.016) and BAL fluid (p<0.05) of IL-6-/- mice was
      significantly higher then their IL-6+/+-injured counterparts. These studies
      suggest that IL-6, while possibly involved in early neutrophil accumulation in
      this model does not appear critical to the development of the TH-2 mediated
      granulomatous vasculitis.

PMID- 17222823
TI  - Enhanced production of p24 Gag protein in HIV-1-infected rat cells fused with
      uninfected human cells.
AB  - Although many human molecules have been suggested to affect replication of human
      immunodeficiency virus type 1 (HIV-1), the distribution of such cofactors in
      human cell types is not well understood. Rat W31/D4R4 fibroblasts expressing
      human CD4 and CXCR4 receptors were infected with HIV-1. The provirus was
      integrated in the host genome, but only a limited amount of p24 Gag protein was
      produced in the cells and culture supernatants. Here we found that p24 production
      was significantly increased by fusing HIV-1-infected W31/D4R4 cells with
      uninfected human cell lines of T-cell, B-cell, or macrophage lineages. These
      findings suggest that human cellular factors supporting HIV-1 replication are
      distributed widely in cells of lymphocyte and macrophage lineages. We also
      examined whether the amount of p24 produced by rat-human hybrid cells was
      correlated with expression levels of specific human genes. The results suggested
      that HP68 and MHC class II transactivator (CIITA) might up- and down-regulate p24
      production, respectively. It was also suggested that HIV-1 replication is
      affected by molecules other than those examined in this study, namely, cyclin T1,
      cyclin-dependent kinase 9, CRM1, HP68, and CIITA.

PMID- 17222824
TI  - Insulin receptor substrates 1 and 2 but not Shc can activate the insulin receptor
      independent of insulin and induce proliferation in CHO-IR cells.
AB  - Ligand-activated insulin receptor (IR) attracts and phosphorylates various
      substrates such as insulin receptor substrates 1-4 (IRS) and Shc. To investigate
      how binding affinity for substrate affects signalling we generated chimeric
      receptors with the beta-chain of the insulin receptor containing NPXY motives
      with different affinities for receptor substrates. We found that the extent of
      receptor tyrosine phosphorylation positively correlates with binding affinity
      towards IRS1/2 but not towards Shc. Moreover, overexpression of IRS1 or IRS2 but
      not of Shc increased IR tyrosine phosphorylation in a dose-dependent manner, also
      independent of insulin. Molecular truncations of IRS1 revealed that neither the
      isolated PH and PTB domains nor the C-terminus with the tyrosine phosphorylation
      sites alone are sufficient for substrate-dependent receptor activation.
      Overexpression of IRS1 and IRS2 impaired insulin-induced internalization of the
      IR in a dose-dependent manner suggesting that IRS proteins prevent endosome
      associated receptor dephosphorylation/inactivation. IRS1 and IRS2 could therefore
      target the activated IR to different cellular compartments. Overexpression of
      IRS1 and IRS2 inhibited insulin-stimulated activation of the MAP kinases Erk1/2
      while it increased/induced activation of Akt/PKB. Finally, overexpression of IRS1
      and IRS2 but not of Shc induced DNA synthesis in starved CHO-IR cells independent
      of exogenous growth factors. Our results demonstrate that variations in cellular
      IRS1 and IRS2 concentration affect insulin signalling both upstream and
      downstream and that IRS proteins could play instructive rather than just
      permissive roles in signal transmission.

PMID- 17222825
TI  - Focus on Molecules: interphotoreceptor retinoid-binding protein (IRBP).

PMID- 17222826
TI  - Effects of ascorbic acid on UV light-mediated photoreceptor damage in isolated
      rat retina.
AB  - Concerns have been raised about whether operating microscopes and
      endoillumination used during ophthalmic surgeries contribute to retinal damage.
      Despite the recognition that ascorbic acid (vitamin C) helps to protect the eye
      from light and the abundance of vitamin C in the retina, artificial aqueous
      humors used during surgery only contain the antioxidant glutathione. To test
      whether inclusion of antioxidants other than glutathione in surgical solutions
      might help to preserve retinal integrity, we studied the effects of vitamin C on
      acute toxicity in isolated rat retinas. Male Sprague-Dawley rats (PND 30+/-2)
      were sacrificed for retinal isolation. In the presence or absence of vitamin C (1
      or 3 mM), retinas were exposed to 302 nm ultraviolet B (UVB) light for 1 h and
      were incubated for a total of 5 h at 30 degrees C. Retinal damage was assessed by
      morphological examination and biochemical assay measuring the amount of lactate
      dehydrogenase (LDH) released from injured cells. In control retinas, LDH release
      was significantly increased after UVB exposure. The presence of 1 mM vitamin C in
      the incubation media significantly reduced LDH release during the post-incubation
      period following UV exposure. No difference was found between 1 and 3 mM vitamin
      C. Microscopic examination revealed that disorganization in the outer nuclear
      layer after UVB exposure was markedly attenuated by administration of 1 mM
      vitamin C. Vitamin C (1 mM), a concentration found in the anterior chamber in
      humans, but not glutathione, prevented phototoxic injury following UV exposure.
      Although vitamin C itself cannot be used in intraocular irrigating solutions
      because of adverse interactions with iron released during bleeding, inclusion of
      antioxidants equivalent to vitamin C should be considered to help protect the
      retina from intraoperative light toxicity.

PMID- 17222827
TI  - Transplantation of bone marrow stromal cells for peripheral nerve repair.
AB  - Cell transplantation using bone marrow stromal cells (BMSCs) to alleviate
      neurological deficits has recently become the focus of research in regenerative
      medicine. Evidence suggests that secretion of various growth-promoting substances
      likely plays an important role in functional recovery against neurological
      diseases. In an attempt to identify a possible mechanism underlying the
      regenerative potential of BMSCs, this study investigated the production and
      possible contribution of neurotrophic factors by transected sciatic nerve defect
      in a rat model with a 15 mm gap. Cultured BMSCs became morphologically
      homogeneous with fibroblast-like shape after ex vivo expansion. We provided
      several pieces of evidence for the beneficial effects of implanted fibroblast
      like BMSCs on sciatic nerve regeneration. When compared to silicone tube control
      animals, this treatment led to (i) improved walking behavior as measured by
      footprint analysis, (ii) reduced loss of gastrocnemius muscle weight and EMG
      magnitude, and (iii) greater number of regenerating axons within the tube.
      Cultured fibroblast-like BMSCs constitutively expressed trophic factors and
      supporting substances, including nerve growth factor (NGF), brain-derived
      neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF),
      ciliary neurotrophic factor (CNTF), collagen, fibronectin, and laminin. The
      progression of the regenerative process after BMSC implantation was accompanied
      by elevated expression of neurotrophic factors at both early and later phases.
      These results taken together, in addition to documented Schwann cell-like
      differentiation, provide evidence indicating the strong association of
      neurotrophic factor production and the regenerative potential of implanted BMSCs.

PMID- 17222828
TI  - GSH-dependent regulation of Fas-mediated caspase-8 activation by acrolein.
AB  - Activation of the cysteine protease caspase-8 by the death receptor Fas (CD95/APO
      1) in B lymphoblastoid SKW6.4 cells or Jurkat T cells is associated with GSH
      depletion. Conversely, GSH depletion by the aldehyde acrolein (3-30 microM) was
      associated with inhibition of Fas-induced caspase-8 activation, although GSH
      depletion by buthionine sulfoximine (BSO) did not affect caspase-8 activation. In
      contrast to BSO, acrolein caused a loss of caspase-8 cysteine content in
      association with direct alkylation of caspase-8. Our findings indicate that
      inhibition of caspase-8 by thiol-reactive agents such as acrolein is not due to
      GSH depletion but caused by direct protein thiol modifications.

PMID- 17222829
TI  - Comparison of the effects of tibolone and estrogen therapy on hemostasis in
      surgical menopause: a randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: To examine the effects of unopposed estrogen (E) and tibolone therapy
      on coagulation and natural anticoagulant systems in surgical menopause. DESIGN: A
      randomized, double-blind, placebo-controlled study. SETTING: University hospital
      clinic in Turkey. PATIENT(S): Ninety healthy surgically postmenopausal women.
      INTERVENTION(S): Ninety surgically postmenopausal women were randomized into
      three groups: unopposed conjugated ET (0.625 mg/d, group 1), tibolone (2.5 mg/d,
      group 2), and identical tablets of placebo (group 3). MAIN OUTCOME MEASURE(S):
      Effects on parameters in the clotting cascade at baseline and after 24 weeks of
      treatment. RESULT(S): After 6 months, fibrinogen, lipoprotein (a), and factor
      VIIa were decreased, and activated partial thromboplastin time was increased
      significantly in the ET group compared with in the placebo group. However,
      tibolone significantly decreased only the serum levels of factor VIIa and factor
      IX and prolonged the activated partial thromboplastin time, compared with placebo
      group. In addition, conjugated ET caused a significantly greater decrease in
      serum fibrinogen level than did tibolone. CONCLUSION(S): Neither E nor tibolone
      therapy led to activation of coagulation in the surgically menopausal women. Both
      preparations changed the overall hemostatic balance to a more fibrinolytic state.

PMID- 17222830
TI  - Reconstruction of ooplasm recipient oocytes with frozen-thawed donor
      microcytoplasts and influence on the microtubular spindle.
AB  - OBJECTIVE(S): To cryopreserve micromanipulated ooplast segments (microcytoplasts)
      from mouse oocytes, compare microcytoplast and parent or recipient oocyte fusion
      performed within or without the zona pellucida, compare electrofusion of fresh or
      frozen oocyte with frozen-thawed microcytoplasts, and assess spindle integrity
      after reconstruction of oocytes. DESIGN: Prospective experimental study. SETTING:
      University-based experimental laboratory. ANIMAL(S): Mouse (MII) oocytes obtained
      after superovulation (n = 363). INTERVENTION(S): Micromanipulation of oocytes (n
      = 363) into microcytoplasts (n = 181), cryopreservation of microcytoplasts along
      with parent and sibling control oocytes (n = 182), reconstruction by
      electrofusion of microcytoplast and parent or recipient oocyte performed with
      (group A, n = 35) or without a zona pellucida (group B, n = 32), comparison of
      electrofusion of fresh oocyte (group C, n = 40) or frozen oocyte (group D, n =
      36) with frozen-thawed microcytoplasts fused within zona, and assessment of
      spindle morphology of reconstructed oocyte. MAIN OUTCOME MEASURE(S): Post-thaw
      survival, success of fusion, and spindle integrity as assessed by immunostaining.
      RESULT(S): Higher success of post-thaw fusion was seen in group A (91.4%)
      compared with group B (56.2%). The post-thaw fusion of microcytoplasts with
      either fresh or frozen oocytes was not significantly different. Spindle integrity
      was 82.5% in group C as compared with 47.2% in group D. CONCLUSION(S):
      Microcytoplasts created from oocytes can be successfully cryopreserved, thawed,
      and used to reconstruct oocytes with intact spindles.

PMID- 17222831
TI  - Interleukin (IL)-12 receptor beta1 codon 378 G homozygote and allele, but not IL
      1 (beta-511 promoter, 3953 exon 5, receptor antagonist), IL-2 114, IL-4-590
      intron 3, IL-8 3'-UTR 2767, and IL-18 105, are associated with higher
      susceptibility to leiomyoma.
AB  - OBJECTIVE: To investigate whether certain polymorphisms are correlated with
      leiomyoma susceptibility, i.e., interleukin (IL)-1, IL-2, IL-4, IL-8, IL-12, and
      IL-18, which are all immunomodulatory cytokines that play important roles in host
      immune responses against cancers. SETTING: Departments of gynecology and genetics
      in a medical center. PATIENT(S): Women were divided into: [1] a leiomyoma group
      (n = 162) and [2] a nonleiomyoma group (n = 156). INTERVENTION(S): Genotyping for
      the IL-1beta-511 promoter, IL-1beta exon 5, IL-1Ra, IL-2 114, IL-4 -590 intron 3,
      IL-8 3'-UTR 2767, IL-12Rbeta1 codon 378, and IL-18 105 were evaluated by
      polymerase chain reaction-restriction fragment length polymorphism. MAIN OUTCOME
      MEASUREMENT(S): Genotypes and allelic frequencies in both groups were compared.
      RESULT(S): Proportions of IL-12Rbeta1 codon 378 *CC/CG/GG in the leiomyoma and
      nonleiomyoma groups were: [1] 7.4%/43.8%/48.8% and [2] 11.5%/54.5%/34%,
      respectively. Distributions of other polymorphisms in both groups were not
      significantly different. Proportions of IL-1beta-511 promoter *CC/CT/TT were: [1]
      22.8%/50%/27.2% and [2] 21.8%/57.1%/21.1% in the leiomyoma and nonleiomyoma
      groups, respectively. The IL-1beta exon 5 *E1 homozygote/heterozygote/E2
      homozygote were: [1] 96.3%/3.7%/0% and [2] 96.9%/3.1%/0% in the leiomyoma and
      nonleiomyoma groups, respectively. Alleles I/II/III/IV/V for IL-1Ra were: [1]
      92.6%/7.1%/0.3%/0/0% and [2] 93.9%/5.7%/0%/0.4/0% in the leiomyoma and
      nonleiomyoma groups, respectively. The IL-2 114 G homozygote/heterozygote/T
      homozygote were: [1] 27.8%/49.4%/22.8% and [2] 20.5%/53.2%/26.3% in the leiomyoma
      and nonleiomyoma groups, respectively. The IL-4 -590 intron 3 *RP1
      homozygote/heterozygote/RP2 homozygote were: [1] 64.8%/32.7%/2.5% and [2]
      69.2%/26.9%/3.9% in the leiomyoma and nonleiomyoma groups, respectively. The IL-8
      3'-UTR 2767 A homozygote/heterozygote/G homozygote were: [1] 14.2%/43.8%/42% and
      [2] 20.5%/41.7%/37.8% in the leiomyoma and nonleiomyoma groups, respectively. The
      IL-18 *AA/AC/CC were: [1] 56.8%/40.7%/2.5% and [2] 59%/39.7%/1.3% in the
      leiomyoma and nonleiomyoma groups, respectively. CONCLUSION(S): The IL-12Rbeta1
      codon 378 *G homozygote and G allele are related to a higher susceptibility to
      leiomyoma. The IL-1beta-511 promoter, IL-1beta exon 5, and IL-1Ra, IL-2 114, IL-4
      -590 intron 3, IL-8 3'-UTR 2767, and IL-18 105 gene polymorphisms are not
      correlated with the development of leiomyoma.

PMID- 17222832
TI  - Care pathways for ectopic pregnancy: a population-based cost-effectiveness
      analysis.
AB  - OBJECTIVE: To define care pathways in terms of frequency, costs, and outcomes and
      to assess their cost-effectiveness. DESIGN: Population-based cost-effectiveness
      study. SETTING: Auvergne EP registry (France). PATIENT(S): Women (n = 1,664)
      registered between 1994 and 2003. INTERVENTION(S): Standard diagnosis and
      treatment of EP. MAIN OUTCOME MEASURE(S): Costs before, during, and after
      hospitalization were assessed from data concerning medical costs of examinations
      and treatments. One-year fertility was used for effectiveness assessment. We
      assessed cost-effectiveness for the healthcare system. RESULT(S): Diagnostic
      ultrasound (47% of scans were nondiagnostic) was essential for the use of
      methotrexate as a first-line treatment for subacute EP. Hospital and ambulatory
      care costs were similar for all surgical-care pathways (diagnostic or
      nondiagnostic ultrasound scan followed by conservative or radical laparoscopy).
      Hospital and ambulatory-care costs associated with methotrexate treatment were
      less than half those for surgical-care pathways. In subacute cases, conservative
      treatments, and methotrexate in particular, were associated with better fertility
      at similar or lower cost to salpingectomy for EP for reproductive failure.
      CONCLUSION(S): Conservative treatments are cost-effective with respect to
      salpingectomy, when subsequent fertility is at stake. Efforts should be made to
      increase the frequency of diagnostic ultrasound scans, making it possible to
      increase methotrexate use and cost-effectiveness.

PMID- 17222833
TI  - Concomitant treatment of severe uterine adenomyosis in a premenopausal woman with
      an aromatase inhibitor and a gonadotropin-releasing hormone agonist.
AB  - OBJECTIVE: To assess the effect of aromatase inhibitors with GnRH agonist for a
      severe symptomatic adenomyosis that is refractory to GnRH agonist and danazol
      with GnRH agonist. DESIGN: Case report. SETTING: Clinical practice in university
      hospital. PATIENT(S): A 34-year-old woman with a complaint of severe
      dysmenorrheal, symptomatic anemia, and a desire to retain fertility.
      INTERVENTION(S): Aromatase inhibitor anastrozole given orally (1.0 mg or 2.0 mg
      daily) for 16 weeks and GnRH agonist given monthly (injected SC, 1.8 mg) for 4
      months. MAIN OUTCOME MEASURE(S): Measurements of uterine volume and levels of
      serum E(2), estrone, A, dehydroepiandrosterone sulfate, LH, FSH, and CA125.
      RESULT(S): Uterine volume was reduced. The reduction rate of uterine volume
      estimated by magnetic resonance imaging and ultrasonography was 60% after 8 weeks
      of treatment. CONCLUSION(S): Aromatase inhibitor with GnRH agonist therapy was
      useful for the management of a severely adenomyotic woman whose desire was for
      conservative treatment.

PMID- 17222834
TI  - Psychological characteristics and marital quality of infertile women registered
      for in vitro fertilization-intracytoplasmic sperm injection in China.
AB  - OBJECTIVE: To assess the psychological health status and marital quality of
      Chinese women who were referred for IVF-intracytoplasmic sperm injection (ICSI),
      to compare the results with a control group, and to test the impact of clinical
      and sociodemographic determinants on psychological health status and marital
      quality in this cohort. DESIGN: A descriptive study of psychological health
      status and marital relationships, comparing infertile women who are registered
      for IVF or IVF-ICSI with fertile controls. SETTING: An assisted reproductive
      center of a science and technology institute of family planning. PATIENT(S): Two
      groups of infertile women (100 registered for IVF, and 100 registered for ICSI),
      and a control group of 100 women attending a gynecology clinic, who have no known
      history of infertility. INTERVENTION: Psychometric tests were administered at the
      first visit of the treatment cycle. MAIN OUTCOME MEASURE(S): Psychological status
      measured by the Hopkins Symptom Checklist-90 (SCL-90), and marital quality
      measured by the ENRICH (Evaluating & Nurturing Relationship Issues, Communication
      & Happiness) marital inventory. RESULT(S): Infertile Chinese women planning to
      undergo IVF-ICSI scored significantly higher on all subscales of the SCL-90 than
      did controls. In addition, women in the IVF subgroup had significantly higher
      scores on depression scales than those in the ICSI subgroup. The study group
      displayed unstable relationships compared to the control group. Age, yearly
      income, duration of infertility, and history of unsuccessful IVF treatment had a
      negative correlation with psychological health status and marital quality.
      CONCLUSION(S): The stresses associated with infertility and IVF treatment had a
      negative impact on Chinese women's psychological health status and marital
      quality. These findings emphasize the need to include psychological and
      sociocultural considerations with any medical interventions for infertility.

PMID- 17222835
TI  - Serum and ovarian Mullerian inhibiting substance, and their decline in
      reproductive aging.
AB  - The objectives of this study were to identify whether there is a decline in
      Mullerian inhibiting substance (MIS) in the female rat during chronological
      aging, and to define the physiological basis of aging-related changes in MIS. The
      results demonstrate that there is an exponential decline in both serum and
      ovarian levels of MIS with increasing female age, and that the histologic origin
      for the reduction in serum levels of MIS is a decline in the number of small
      ovarian follicles expressing MIS.

PMID- 17222836
TI  - Luminal suture thread as a guide for anastomosis: a new vasovasostomy technique.
AB  - OBJECTIVE: To use a new vasovasostomy technique for reversal of vasectomy.
      DESIGN: Case report. SETTING: Clinical and academic research environment.
      PATIENT: A patient who had undergone vasectomy. INTERVENTION: We used 4/0 prolene
      as a guide during anastomosis for reversal of vasectomy. MAIN OUTCOME MEASURE:
      Semen analysis. RESULT(S): Three months after the operation, the spermiogram
      showed the sperm count, the percentage of normal morphologic sperm, progressive
      motility, and vitality as 9 million/L, 70%, 33%, and 60%, respectively. Six
      months later, the spermiogram was repeated and the following results were
      obtained: the sperm count, the percentage of normal morphologic sperm,
      progressive motility, and vitality as 14 million/L, 65%, 40%, and 65%,
      respectively. CONCLUSION(S): This new technique is cost-effective, easy, cheap,
      and less time-consuming, and has a high success rate.

PMID- 17222837
TI  - Information-sharing among couples considering multifetal pregnancy reduction.
AB  - OBJECTIVE: To determine the information-sharing strategies of couples considering
      fetal reduction, and the impact of these strategies on the chances of
      encountering hostility in their social networks. DESIGN: Cross-sectional design
      of semistructured qualitative interviews, coded with respect to sharing
      strategies and level of personally directed hostility encountered. SETTING:
      Multiple Pregnancy Management Program, Comprehensive Genetics, New York, New
      York. PATIENT(S) AND INTERVENTION(S): Fifty women and their partners who were
      making a first visit to our maternal-fetal management facility, in order to
      consider the possibility of multifetal reduction as a pregnancy-management
      strategy. MAIN OUTCOME MEASURE(S): Development of information-sharing strategies,
      and the chances of encountering personally directed hostility regarding
      multifetal reduction associated with more and less selective strategies.
      RESULT(S): Four information-sharing strategies emerged from the analysis. Two of
      these strategies were relatively open (extended network, and both parents). Two
      other strategies were relatively selective (qualified family and friends, and
      defended relationship). The selective strategies were significantly less likely
      to encounter to encounter personally directed hostility (odds ratio, 3.88; 95%
      confidence intervals, 0.87-17.30). CONCLUSION(S): Selective sharing of
      information for couples considering multifetal prgnancy reduction is a
      potentially useful strategy for moderating potentially stressful relationships in
      their social networks. Clinics should find a way of integrating the discussion of
      selective sharing into their clinic's cultural repertoire of patient-support
      services.

PMID- 17222838
TI  - Novel method to characterize primary cultures of leiomyoma and myometrium with
      the use of confirmatory biomarker gene arrays.
AB  - OBJECTIVE: To develop a rapid biomarker method for confirming that leiomyoma and
      myometrium primary cultures maintain the molecular phenotype of the progenitor
      tissues. DESIGN: Confirmation of primary cultures from leiomyoma and myometrium
      tissues. SETTING: University hospital. PATIENT(S): Women undergoing hysterectomy
      for symptomatic leiomyomas. INTERVENTION(S): Primary cell cultures, reverse
      transcriptase polymerase chain reaction (RT-PCR), microarray, real time RT-PCR,
      and immunofluorescence. MAIN OUTCOME MEASURE: Relative messenger RNA and protein
      expression in leiomyoma and myometrial cell cultures. RESULT(S): We developed
      primary cell cultures from human leiomyoma and patient-matched myometrium
      obtained from hysterectomy specimens. In the primary cultures, we confirmed the
      presence of smooth muscle-specific alpha-actin as well as filamentous actin.
      Based on microarray analysis, we expected and confirmed, in the progenitor tissue
      and derived primary cultures, an overexpression of versican (8.31 fold +/- 2.2
      SEM and 4.3 fold +/- 1.01 SEM, respectively), transforming growth factor beta-3
      (5.66 fold +/- 0.82 SEM and 4.92 fold +/- 0.58 SEM, respectively), and cytochrome
      P450-26A1 (6.76 fold +/- 0.80 SEM and 6.17 fold +/- 2.02 SEM, respectively), and
      an underexpression of dermatopontin (-5.6 fold +/- 1.82 SEM and -3.41 +/- 1.20
      SEM, respectively). CONCLUSION(S): Primary cell cultures offer a reliable in
      vitro model system for leiomyoma disease, if confirmed. Analysis of a gene array
      that distinguishes between myometrium and leiomyoma molecular phenotypes offers a
      rapid and reliable confirmation method, and provides confidence that in vitro
      findings resemble in vivo disease.

PMID- 17222839
TI  - Isolated type 5 antimitochondrial autoantibodies are associated with a history of
      thrombocytopenia and fetal loss.
AB  - OBJECTIVE: To report an unusual case of clinical antiphospholipid syndrome seen
      with recurrent fetal loss, chronic thrombocytopenia, and recurrent idiopathic
      thrombocytopenic purpura, in which the only laboratory marker was M5-type
      antimitochondrial autoantibodies (AMA). DESIGN: Case report. SETTING: University
      general hospital, tertiary level of clinical care. Institutional practice.
      PATIENT(S): A 65-year-old woman with antiphospholipid syndrome associated with
      autoimmune polyglandular syndrome of IIIC type. INTERVENTION(S): Clinical history
      and biochemical and immunologic markers. MAIN OUTCOME MEASURE(S): The presence of
      M5-type AMA in clinical antiphospholipid syndrome isolated by indirect
      immunofluorescence. RESULT(S): During the 10-year follow-up, immunologic studies
      detected a persistent positive M5-type AMA at high titer (1/640), antithyroid
      antibodies, anti-gastric parietal cells, and anti-intrinsic factor. Antinuclear,
      anti-DNA, and antiphospholipid (anticardiolipin, anti-beta(2)-glycoprotein I)
      autoantibody tests were all repeatedly negative. Results of coagulation studies
      and negative lupus anticoagulant were normal on several occasions. CONCLUSION(S):
      Our findings suggest the necessity of determining M5-type AMA in the study panel
      of antiphospholipid syndrome diagnosis, particularly in the absence of other
      typical autoantibodies.

PMID- 17222840
TI  - Ecdysteroid levels in Daphnia magna during a molt cycle: determination by
      radioimmunoassay (RIA) and liquid chromatography-mass spectrometry (LC-MS).
AB  - Despite their abundance and their enormous significance for various ecological
      processes, endocrine systems of microcrustaceans have been poorly investigated.
      Here, we used a highly sensitive radioimmunoassay (RIA) to determine free and
      conjugated ecdysteroid levels in whole-body extracts of adult Daphnia magna
      during a complete molt cycle. Ecdysteroid levels were predominated by free
      ecdysteroids. Starting from basal levels in the postmolt stage the concentration
      of free ecdysteroids increased sharply in the early premolt stage, followed by a
      sharp decline back to basal levels just prior to ecdysis. Polar and apolar
      ecdysteroid conjugates were found in rather low amounts with little variation
      during the molt cycle. Only small amounts of ecdysteroids were found in newly
      deposited eggs of D. magna, which suggest a sparing investment of maternal
      ecdysteroids into the eggs for early embryogenesis. As in whole-body extracts,
      free ecdysteroids were the predominant ecdysteroids found in eggs of D. magna,
      together with small amounts of polar and intermediary amounts of apolar
      conjugates. Hence, the pathways leading to polar and apolar ecdysteroid
      conjugates appear to be of minor importance in D. magna. Analyses of the
      immunodetectable peak in free ecdysteroids by liquid chromatography-mass
      spectrometry (LC-MS) revealed that molting is induced most probably by an
      increased level of 20-hydroxyecdysone. Microcrustaceans of the genus Daphnia are
      key components in freshwater food webs. Examination of the functional role of
      ecdysteroids in controlling developmental processes might help to understand the
      performance of the herbivorous grazer in its environment, in particular with
      regard to the adverse effects of environmental xenobiotics acting as endocrine
      disrupters.

PMID- 17222841
TI  - Changes in hepatic gene expression related to innate immunity, growth and iron
      metabolism in GH-transgenic amago salmon (Oncorhynchus masou) by cDNA subtraction
      and microarray analysis, and serum lysozyme activity.
AB  - Growth hormone (GH) transgenic amago salmon (Oncorhynchus masou) were generated
      with a construct containing the sockeye salmon GH1 gene fused to the
      metallothionein-B (MT-B) promoter from the same species. This transgene directed
      significant growth enhancement with transgenic fish reaching approximately four
      to five times greater weight than control salmon in F(2) and F(3) generations.
      This drastic growth enhancement by GH transgene is well known in fish species
      compared with mammals, however, such fish can show morphological abnormalities
      and physiological disorders like other GH transgenic animals. GH is known to have
      many acute effects, but currently there are no data describing the chronic
      effects of over-expression of GH on various hepatic genes in GH transgenic fish.
      Hepatic gene expression is anticipated to play very important roles in many
      physiological functions and growth performance of transgenic and control salmon.
      To examine these effects, we performed subtractive hybridization (using cDNA
      generated from liver RNA) in both directions to identify genes both increased and
      decreased in transgenic salmon relative to controls (576 clones were isolated and
      sequenced in total). Heme oxygenase, vitelline envelope protein, Acyl-coA binding
      protein, NADH dehydrogenase, mannose binding lectin-associated serine protease,
      hemopexin-like protein, leucyte-derived chemotaxin2 (LECT2), and many other genes
      were obtained in higher clone frequencies suggesting enhanced expression. In
      contrast, complement C3-1, lectin, rabin, alcohol dehydrogenase, Tc1-like
      transposase, Delta6-desaturase, and pentraxin genes were obtained in lower
      frequencies. Microarray analysis was also performed to obtain quantitative
      expression data for these subtracted cDNA clones. Analysis of fish across seasons
      was also conducted using both F(2) and F(3) salmon. Results of the microarray
      data essentially corresponded with those of the subtraction data when both F(2)
      and F(3) fish were completely immature, but the expression pattern was changed
      when fish approached maturation. Genes showing enhanced expression in GH
      transgenic fish in F(2) and F(3) by array analysis were vitelline envelope
      protein, hemopexin-like protein, heme-oxygenase, inter alpha-trypsin inhibitor,
      LECT2, GTP cyclohydrolase I feedback regulatory protein (GFRP), and bikunin.
      Reduced expression genes were lectin, Delta6-desaturase, apolipoprotein, and
      pentraxin. In particular, lectin was found to be highly suppressed in all F(2)
      and immature F(3) salmon. Further, serum lysozyme activity, one of innate
      immunity, was significantly (p<0.05) decreased in both F(2) and F(3) GH
      transgenic fish. These results indicate that the GH transgene fish had altered
      hepatic gene expression relating to iron-metabolism, innate immunity,
      reproduction, and growth.

PMID- 17222842
TI  - Molecular characterization and gene expression pattern of two putative molt
      inhibiting hormones from Litopenaeus vannamei.
AB  - Two cDNA sequences (Liv-MIH1 and Liv-MIH2) were cloned from the eyestalk ganglia
      of the white shrimp Litopenaeus vannamei. The conceptually translated peptide
      precursors consist of a mature peptide (77 residues for Liv-MIH1, 75 residues for
      Liv-MIH2), preceded by a 28-residue signal peptide. Both mature peptides share
      highest sequence identity with other known MIHs, and contain several conserved
      residues that have been proposed to be functionally critical for MIH activity.
      Analysis of genomic sequences reveals that both genes are organized in a 3 exon/2
      intron manner, with the same sites of intron insertion. The transcripts of Liv
      MIH1 and Liv-MIH2 were detected exclusively in the eyestalk, but not in other
      neural and non-neural tissues examined. Phylogenetic analysis indicates that Liv
      MIH1 and Liv-MIH2 cluster with the type II peptides that are considered as
      penaeid MIH. In addition, a quantitative real-time polymerase chain reaction
      (PCR) assay was developed and validated for the quantification of gene expression
      of Liv-MIH1 and Liv-MIH2. Transcript levels for both genes remained constant
      through stages A - D(1') (ranges of relative expression levels are 97.9+/-2.9 to
      104.5+/-8.9% for Liv-MIH1, and 85.6+/-6.7 to 104.7+/-10.8% for Liv-MIH2), and
      declined afterwards, reaching a lowest level during stage D(2)D(3) (40.6+/-0.4%
      for Liv-MIH1, and 48.5+/-3.2% for Liv-MIH2). These significant decreases in the
      transcript levels correspond to a significant increase in hemolymph ecdysteroid
      titers at stage D(2)D(3). These results clearly indicate that Liv-MIH1 and Liv
      MIH2 are type II peptides of the crustacean hyperglycemic hormone family and most
      likely function as MIHs in the white shrimp. They are discussed with regard to
      the presence of multiple MIHs and possible functional divergence of type II
      peptides in Penaeidae, as well as endocrine regulation of crustacean molting.

PMID- 17222843
TI  - Non-union of Weber B fractures: a case series.

PMID- 17222844
TI  - Characterization of glutamine: fructose-6-phosphate aminotransferase from the
      ixodid tick, Haemaphysalis longicornis, and its critical role in host blood
      feeding.
AB  - Glutamine: fructose-6-phosphate aminotransferase (GFAT, EC2.6.1.16) is the first,
      and rate-limiting, enzyme in the hexosamine biosynthetic pathway, and is involved
      in the regulation of chitin biosynthesis and glycosylation of proteins. We report
      here the molecular characterization and potential functions of a novel GFAT
      (HlGFAT) from the ixodid tick Haemaphysalis longicornis. HlGFAT consists of 696
      amino acids, possesses a class II glutamine aminotransferase domain and two sugar
      isomerase motifs, and has a close phylogenetic relationship to insect GFAT.
      HlGFAT was expressed at all stages of development and in multiple organs. The
      transcription levels in the cuticle and midgut were enhanced significantly by
      blood feeding during the first 3 days and decreased on the fifth day, while those
      in salivary glands maintained almost the same level during the first 3 days, and
      decreased to a rather low level at 5 days postinfestation. Endogenous HlGFAT was
      identified at all developmental stages and in multiple organs, such as epidermis,
      midgut epithelium, salivary gland, ovary, Malpigian's tubule and trachea. It was
      identified as a protein of 78.4 kDa using Western blot analysis. Following RNA
      interference of HlGFAT, engorgement by adult females was reduced significantly.
      One of the potential mechanisms for this effect may be that the inhibition of
      HlGFAT limits chitin biosynthesis, so disrupting cuticle growth and possibly
      peritrophic matrix formation during blood feeding.

PMID- 17222845
TI  - Linkage Group Selection--a fast approach to the genetic analysis of malaria
      parasites.
AB  - Genetic analysis of malaria parasites has shown that the mechanisms of
      inheritance in these organisms are classically Mendelian. In other words, alleles
      of genes at different loci recombine, and alleles at the same gene locus
      segregate, in the progeny of a genetic cross between two genetically distinct
      lines of malaria parasite. Importantly, such progeny are haploid in the first
      filial generation following genetic crossing. Consequently, genetic analysis,
      including linkage analysis, can be done directly upon the cloned cross progeny.
      Linkage analysis conducted upon the progeny of genetic crosses between malaria
      parasites can lead to the location of a single gene controlling a specific
      phenotype, as has been achieved to identify the gene for chloroquine resistance
      in Plasmodium falciparum. The work involved, however, is extremely labour
      intensive. It involves the generation of many hundreds, to a thousand or so, of
      independent recombinant clones from the cross progeny and the biological
      characterisation, and genetic typing for hundreds of molecular genetic markers of
      each such clone. We discuss here a fast-track method for identifying genes
      controlling specific phenotypes, e.g. drug resistance/sensitivity. It involves
      the mass screening with quantitative molecular genetic markers of the uncloned
      progeny of a genetic cross following its growth under a selection pressure
      representing the phenotype of interest. We have called the method Linkage Group
      Selection.

PMID- 17222846
TI  - Schistosome membrane proteins as vaccines.
AB  - Schistosomes are parasitic blood flukes that infect approximately 200 million
      people and are arguably the most important human helminth in terms of mortality.
      The outermost surface of intra-mammalian stages of the parasite, the tegument, is
      the key to the parasite's success, but it is also generally viewed as the most
      susceptible target for vaccines and drugs. Over the past 2 years the proteome of
      the Schistosoma mansoni tegument has been investigated and these studies revealed
      surprisingly few proteins that are predicted to be accessible to the host immune
      response, namely proteins with at least one membrane-spanning domain. However, of
      this handful of proteins, some are showing great promise as recombinant vaccines
      against schistosomiasis at a pre-clinical level. In particular, the tetraspanin
      family of integral membrane proteins appears to be abundantly represented in the
      tegument, and convergent data using the mouse vaccine model and correlates of
      protective immunity in naturally exposed people suggests that this family of
      membrane proteins offer great promise for schistosomiasis vaccines. With the
      recent advances in schistosome genomics and proteomics, a new suite of potential
      vaccine antigens are presented and these warrant detailed investigation and
      appropriate funding over the next few years.

PMID- 17222847
TI  - Rare APOA5 mutations--clinical consequences, metabolic and functional effects: an
      ENID review.
AB  - In 2001, a gene encoding a novel apolipoprotein (apo), APOA5, was identified by
      comparative human/mouse sequencing. The encoded protein, apoAV, had been missed
      in routine apolipoprotein identification because it occurs at very low plasma
      concentrations and only DNA analysis led to its identification. Knockout and
      transgenic mouse models of apoAV showed an inverse relationship with plasma
      triglyceride levels. In human studies, common APOA5 variants have shown near
      consistent association with elevated plasma TG levels, confirming apoAV as
      playing a role in human triglyceride metabolism. Based on mouse knockout models
      it was predicted that individuals with rare mutations in APOA5 would present with
      severe hypertriglyceridaemia and apoAV deficiency. However, considering the small
      number of mutation carriers identified to date, the mode of inheritance is
      variable and in the recessive form TG levels are within the normal range, and
      apoAV deficiency only occurs in the homozygous state. Furthermore, penetrance of
      the mutations is low and appears to require co-inheritance of a common APOA5 TG
      raising allele as well as environmental factors for expression of the
      hypertriglyceridaemia. In this review the clinical and metabolic consequences and
      phenotype of the three APOA5 mutations reported to date, which lead to premature
      truncations of apoAV are described. The insight these truncated protein give to
      the structure-function relationship of apoAV is explored and the relative
      importance of plasma and liver apoAV discussed.

PMID- 17222848
TI  - Association of telomere shortening with impaired glucose tolerance and diabetic
      macroangiopathy.
AB  - OBJECTIVE: Shortening of telomere length has been reported in several conditions
      including Type 2 diabetes and atherosclerosis. The aims of this study were (1) to
      assess whether telomere shortening occurs at the stage of pre-diabetes, i.e.,
      impaired glucose tolerance (IGT) and (2) whether telomere shortening was greater
      in Type 2 diabetic subjects with atherosclerotic plaques. METHODS: Subjects with
      impaired glucose tolerance (IGT) (n=30), non-diabetic control subjects (n=30),
      Type 2 diabetic patients without (n=30) and with atherosclerotic plaques (n=30)
      were selected from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing
      epidemiological population-based study. Southern-blot analysis was used to
      determine mean terminal restriction fragment (TRF) length, a measure of average
      telomere size, in leukocyte DNA. Levels of thiobarbituric acid reactive
      substances (TBARS), protein carbonyl content (PCO) and high sensitive C-reactive
      protein (hs-CRP) were measured by standard methodologies. Carotid intima-media
      thickness (IMT) was assessed by high resolution B-mode ultrasonography. RESULTS:
      The mean (+/-S.E.) TRF lengths were significantly lower in IGT subjects (6.97+/
      0.3 kb; p=0.002) and lower still in Type 2 diabetic subjects without plaques
      (6.21+/-0.2; p=0.0001) and lowest in Type 2 diabetic subjects with
      atherosclerotic plaques (5.39+/-0.2; p=0.0001) when compared to control subjects
      (8.7+/-0.5). In IGT subjects, TRF length was positively correlated to HDL
      cholesterol and negatively correlated to glycated hemoglobin (HbA1c), TBARS, PCO,
      HOMA-IR and IMT. In multiple linear regression analysis, presence of diabetes,
      HDL cholesterol and increased TBARS levels appear as significant determinants of
      telomere shortening. CONCLUSION: Telomere shortening is seen even at the stage of
      IGT. Among subjects with Type 2 diabetes, those with atherosclerotic plaques had
      greater shortening of telomere length compared to those without plaques.

PMID- 17222849
TI  - Arterial wall permeability at the left coronary bifurcation.

PMID- 17222850
TI  - Increasing levels of TNFalpha are associated with increased brain perfusion.
AB  - OBJECTIVE: Recent reports of animal models have shown that growth factors have
      stimulating effect on brain perfusion via the development of blood vessels.
      However, studies on the effect of growth factors on brain perfusion in humans are
      lacking. The aim of our study was to prospectively investigate in humans the
      relation between growth factors and brain perfusion. METHODS: We analyzed
      circulating levels of vascular endothelial growth factor (VEGF), granulocyte
      macrophage colony-stimulating growth factor (GM-CSF), tumor necrosis factor alpha
      (TNFalpha) and basic fibroblast growth factor (bFGF) in 121 consecutive patients
      (99 men and 22 women, age 58+/-10 years) who were enrolled in a prospective
      cohort study of patients with symptomatic atherosclerotic disease. In all
      patients regional cerebral blood flow (rCBF; in mL/min/100g) measurements were
      performed with arterial spin labeling magnetic resonance imaging. Cerebrovascular
      risk factors were assessed by means of a questionnaire and physical,
      ultrasonographic and laboratory examination. RESULTS: Increasing levels of
      TNFalpha were significantly associated with a higher rCBF (beta=7.0; 95%
      confidence interval 0.7; 13.9), independent of the presence of cerebrovascular
      risk factors. No significant association was found for VEGF, GM-CSF and bFGF.
      CONCLUSIONS: Increasing levels of TNFalpha are associated with increased rCBF,
      independent of the presence of cerebrovascular risk factors.

PMID- 17222851
TI  - Are LXR-regulated genes a major molecular target of plant sterols/stanols?

PMID- 17222852
TI  - The generalized triphasic correspondence principle for simultaneous determination
      of the mechanical properties and proteoglycan content of articular cartilage by
      indentation.
AB  - The triphasic mixture theory has been used to describe the mechanical and
      physicochemical behaviors of articular cartilage under some specialized loading
      conditions. However, the mathematical complexities of this theory have limited
      its applications for theoretical analyses of experimental studies and models for
      predicting cartilage and other biological tissues' deformational behaviors. A
      generalized correspondence principle has been established in the present study,
      and this principle shows that the equilibrium deformational behavior of a charged
      hydrated material under loading is identical to that of an elastic medium without
      charge. A set of explicit formulas has been derived to correlate the mechanical
      properties of an equivalent material with the intrinsic elastic moduli, fixed
      charge density and free-ion concentration within the cartilage tissue. The
      validity of these formulas is independent of the deformation state of the elastic
      solid matrix under an infinitesimal strain. Therefore they can be employed for
      any loading conditions, such as confined or unconfined compression, tension, and
      indentation tests, etc. In the current study, the fixed charge density of bovine
      cartilage is determined from the indentation creep data using this generalized
      correspondence principle. The proteoglycan content results were then compared
      with those from biochemical assay, yielding a linear regression slope of 1.034.
      Additionally a correspondence principle within a framework of cubic symmetry and
      a bilinear response in tension-compression (the conewise linear elasticity model)
      has also been developed to demonstrate the potential application of current
      methodology for inhomogeneous, anisotropic and nonlinear situations.

PMID- 17222853
TI  - Shoulder function: the perfect compromise between mobility and stability.
AB  - Shoulder function is a compromise between mobility and stability. Its large
      mobility is based on the structure of the glenohumeral joint and simultaneous
      motion of all segments of the shoulder girdle. This requires fine-tuned muscle
      coordination. Given the joint's mobility, stability is mainly based on active
      muscle control with only a minor role for the glenohumeral capsule, labrum and
      ligaments. In this review factors influencing stability and mobility and their
      consequences for strength are discussed, with special attention to the effects of
      morphology, muscle function and sensory information.

PMID- 17222854
TI  - Development of a perfusion ion-exchange chromatography method for the separation
      of soybean proteins and its application to cultivar characterization.
AB  - A perfusion ion-exchange chromatography method has been designed, for the first
      time, for the separation of soybean proteins and its application to the
      characterization of soybean cultivars. For that purpose, the gradient, the mobile
      phase composition (buffer concentration, buffer pH, and elution salt), and the
      temperature were optimized. The method consisted of a two-step gradient (0% B for
      2 min and from 0 to 50% B in 10 min) being mobile phase A a 2 0mM borate buffer
      (pH 9) and mobile phase B a 20 mM borate buffer (pH 9) containing 1M sodium
      chloride. The procedure used for the preparation of sample solutions was
      significantly simpler than that proposed by other authors and basically consisted
      of dissolving in water. This method enabled the separation of soybean proteins
      from a soybean protein isolate in 11 peaks in about 9 min. The method was used to
      separate soybean proteins in different commercial soybeans. In general, the 11
      peaks yielded by the soybean protein isolate were also observed in the
      chromatograms of all soybeans. However, the area percentages of every peak in
      every soybean enabled the differentiation between soybeans. Moreover, the method
      was also used to separate soybean proteins in the proteic fractions obtained from
      every soybean. Multivariate methods were used for patterns recognition and the
      classification of samples.

PMID- 17222855
TI  - The influence of major components on the direct chromatographic recovery of a
      protein from transgenic milk.
AB  - This work presents a systematic evaluation of the influence of lipids and casein
      on the performance of a chromatographic capture step for the recovery of a target
      protein from transgenic milk. Lactoperoxidase (LPO) was spiked at concentrations
      typical of those to be expected for transgenic proteins in commercial bovine milk
      and the dynamic adsorption of LPO to fixed beds of SP Sepharose FF studied in
      frontal analysis experiments. By removing successively selected components from
      whole milk, their individual influence on the dynamic adsorption behaviour of LPO
      could be studied. A mathematical model, fitted to the breakthrough curves of LPO,
      provided a quantitative measure of parameters describing mass transfer and
      adsorption in the column. A significant reduction in column capacity for LPO in
      the presence of milk or whey was recorded, which could be attributed to competing
      adsorption of alkaline earth metal ions to the cation exchange resin. While the
      high concentrations of lipids present in whole milk did strongly reduce the
      column permeability, no significant influence of either casein or low
      concentrations of lipids on the hydraulic properties of columns or on the
      adsorption of LPO could be detected. The results indicate that chromatography,
      which forms an essential part of all current large-scale processes for the
      recovery of proteins from transgenic milk, could potentially be moved further
      upstream. Alternatively, existing operations for the removal of lipid and casein
      could be re-designed so as to maximise product yields. This suggests that
      significant product losses during current pre-chromatography milk purification
      could be reduced or potentially even avoided.

PMID- 17222856
TI  - Identification of N-gluconyl [corrected] ethanolamine in wine by negative
      electrospray ionization with post-column chloride attachment and accurate mass
      determination on a triple-quadrupole mass spectrometer.
AB  - In this study a specific taste modulating flavour-ingredient, N-gluconyl
      [corrected] ethanolamine, was determined in two Beerenauslese wines using two
      different LC-MS techniques. For a first screening LC-MS(2) on an ion-trap mass
      spectrometer with negative electrospray ionization (ESI(-)) was applied.
      Sensitivity (and selectivity) was successfully increased approx. 10-fold by post
      column addition of chloroform to form [M+Cl](-) species. In a second step LC
      MS(2) on a triple-quadrupole mass spectrometer in accurate mass mode confirmed
      the presence of N-gluconyl [corrected] ethanolamine in wine. The application of
      the right MS(2) transitions for an unambiguous identification is discussed. N
      Gluconyl [corrected] ethanolamine concentrations in the wines were found to be
      1.1 and 4.0 microg/l.

PMID- 17222857
TI  - Gas chromatography-mass spectrometry analysis of amino acid enantiomers as methyl
      chloroformate derivatives: application to space analysis.
AB  - This work describes a GC-MS method for enantioselective separation of amino
      acids. The method is based on a derivatization reaction which employs a mixture
      of alkyl chloroformate-alcohol-pyridine, as reagents to obtain the N(O,S)-alkyl
      alkoxy carbonyl esters of amino acids. Various reaction parameters are
      investigated and optimized to achieve a reproducible derivatization procedure
      suitable for separation of amino acid enantiomers on Chirasil-L-Val chiral
      stationary phase. In particular, the following topics are investigated for 20
      proteinogenic amino acids: (i) the proper reagent and reaction conditions to
      obtain the highest derivative yield; (ii) the amino acid reactivity and the MS
      properties of the obtained derivatives; (iii) the linearity and sensitivity of
      the analytical method; (iv) the retention behavior of the derivatives and their
      enantiomeric separation on the Chirasil-L-Val chiral stationary phase. By
      combining the resolution power of the Chirasil-L-Val column and the high
      selectivity of the SIM MS detection mode, the described procedure enables the
      enantiomeric separation and quantification of 16 enantiomeric pairs of amino
      acids. The procedure is simple and fast and reproducible. It displays a wide
      linearity range at ppb detection limits for quantitative determinations: these
      properties make this derivatization method a suitable candidate for amino acid GC
      MS analysis on board of the spacecrafts in space exploration missions of solar
      system body environments.

PMID- 17222858
TI  - Reversed-phase high-performance liquid chromatographic separation of inorganic
      mercury and methylmercury driven by their different coordination chemistry
      towards thiols.
AB  - Since mercuric mercury (Hg(2+)) and methylmercury (CH(3)Hg(+)) display different
      toxicological properties in mammals, methods for their quantification in dietary
      items must be available. Employing Hg-specific detection, we have developed a
      rapid, isocratic, and affordable RP-HPLC separation of these mercurials using
      thiol-containing mobile phases. Optimal separation was achieved with a 50mM
      phosphate-buffer containing 10mM L-cysteine at pH 7.5. The separation is driven
      by the on-column formation of complexes between each mercurial and L-cysteine,
      which are then separated according to their different hydrophobicities. The
      developed method is compatible with inductively coupled plasma atomic emission
      spectrometry and was applied to analyze spiked human urine.

PMID- 17222859
TI  - Indirect amperometric measurement of electroosmotic flow rates and effective
      mobilities in microchip capillary electrophoresis.
AB  - End-channel indirect amperometry is based on the principle of Kohlrausch
      regulating function (KRF). A dilute electroactive ionic species is added to the
      background electrolyte as a continuously eluting electrophore, which is used as
      probe. The probe concentration variation with the omega value of KRF in the
      sampling zone was described schematically in this report. Either cathodic or
      anodic electroosmotic flow (EOF) rates were monitored in microchip. There was no
      significant difference between the values of EOF rates measured by present method
      and current-monitoring method. Detection of electroactive and nonelectroactive
      analytes can also be accomplished by indirect amperometric method. Hence, the
      effective mobility of analytes can be accurately calculated. And the response
      mechanism of nonelectroactive analytes K(+), Na(+) and Li(+) in the indirect
      method was speculated.

PMID- 17222860
TI  - Rapid purification and scale-up of honokiol and magnolol using high-capacity high
      speed counter-current chromatography.
AB  - In this paper, a rapid separation approach has been developed using high-capacity
      high-speed counter-current chromatography (high-capacity HSCCC) to isolate and
      purify honokiol and magnolol, which are the main bioactive constituents from
      Houpu. The optimization of the solvent selection process, sample loading volume
      and flow rate is systematically studied using analytical high-capacity HSCCC. The
      optimized parameters obtained rapidly at analytical scale were used for a 1000 x
      scale-up preparative run using pilot scale high-capacity HSCCC in a MAXI-DE
      centrifuge. A crude sample of 43 g was successfully separated and the fractions
      were analysed by high-performance liquid chromatography (HPLC). This large scale
      preparative single step run yielded 16.9 and 19.4 g of honokiol and magnolol with
      purities of 98.6 and 99.9%, in only 20 min. This is the first time that high
      performance counter-current chromatography has been used to purify multiple gram
      grade bioactive compounds in less than 1h and at such high concentrations of
      final products (10.8 g/l for magnolol and 7.0 g/l for honokiol).

PMID- 17222861
TI  - Method validation for the analysis of 169 pesticides in soya grain, without clean
      up, by liquid chromatography-tandem mass spectrometry using positive and negative
      electrospray ionization.
AB  - Part of a comprehensive study on the comparison of different extraction methods,
      GC-MS(/MS) and LC-MS/MS detection methods and modes, for the analysis of soya
      samples is described in this paper. The validation of an acetone-based extraction
      method for analysis of 169 pesticides in soya, using LC-MS/MS positive and
      negative electrospray ionisation (ESI) mode, is reported. Samples (5 g) were
      soaked with 10 g water and subsequently extracted with 100 mL of a mixture of
      acetone, dichloromethane and light petroleum (1:1:1), in the presence of 15 g
      anhydrous sodium sulphate. After centrifugation, aliquots of the extract were
      evaporated and reconstituted in 1.0 mL of methanol, before direct injection of
      the final extract (corresponding with 0.05 g soya mL(-1)) into the LC-MS/MS
      system. Linearity, r(2) of calibration curves, instrument limit of
      detection/quantitation (LOD/LOQ) and matrix effect were evaluated, based on seven
      concentrations measured in 6-fold. Good linearity (at least r(2)> or =0.99) of
      the calibration curves was obtained over the range from 0.1 or 0.25 to 10.0 ng
      mL(-1), corresponding with pesticide concentrations in soya bean extract of 2 or
      5-200 microg kg(-1). Instrument LOD values generally were 0.1 or 0.25 ng mL(-1).
      Matrix effects were negligible for approximately 90% of the pesticides. The
      accuracy, precision and method LOQ were determined via recovery experiments,
      spiking soya at 10, 50, 100 microg kg(-1), six replicates per level. In both ESI
      modes, method LOQ values were mostly 10 or 50 microg kg(-1) and more than 70% of
      pesticides analysed by each mode met the acceptability criteria of recovery (70
      120%) and RSD (< or =20%), at one or more of the three levels studied. A fast,
      easy and efficient method with acceptable performance was achieved for a
      difficult matrix as soya, without cleanup.

PMID- 17222862
TI  - Acclimation effects on thermal tolerances of springtails from sub-Antarctic
      Marion Island: indigenous and invasive species.
AB  - Collembola are abundant and functionally significant arthropods in sub-Antarctic
      terrestrial ecosystems, and their importance has increased as a consequence of
      the many invasive alien species that have been introduced to the region. It has
      also been predicted that current and future climate change will favour alien over
      indigenous species as a consequence of more favourable responses to warming in
      the former. It is therefore surprising that little is known about the
      environmental physiology of sub-Antarctic springtails and that few studies have
      explicitly tested the hypothesis that invasive species will outperform indigenous
      ones under warmer conditions. Here we present thermal tolerance data on three
      invasive (Pogonognathellus flavescens, Isotomurus cf. palustris, Ceratophysella
      denticulata) and two indigenous (Cryptopygus antarcticus, Tullbergia bisetosa)
      species of springtails from Marion Island, explicitly testing the idea that
      consistent differences exist between the indigenous and invasive species both in
      their absolute limits and the ways in which they respond to acclimation (at
      temperatures from 0 to 20 degrees C). Phenotypic plasticity is the first in a
      series of ways in which organisms might respond to altered environments. Using a
      poorly explored, but highly appropriate technique, we demonstrate that in these
      species the crystallization temperature (Tc) is equal to the lower lethal
      temperature. We also show that cooling rate (1 degree C min(-1); 0.1 degrees C
      min(-1); 0.5 degrees C h(-1) from 5 to -1 degrees C followed by 0.1 degrees C
      min(-1)) has little effect on Tc. The indigenous species typically have low Tcs
      (c. -20 to -13 degrees C depending on the acclimation temperature), whilst those
      of the invasive species tend to be higher (c. -12 to -6 degrees C) at the lower
      acclimation temperatures. However, Ceratophysella denticulata is an exception
      with a low Tc (c. -20 to -18 degrees C), and in P. flavescens acclimation to 20
      degrees C results in a pronounced decline in Tc. In general, the invasive and
      alien species do not differ substantially in acclimation effects on Tc (with the
      exception of the strong response in P. flavescens). Upper lethal temperatures
      (ULT50) are typically higher in the invasive (33-37 degrees C) than in the
      indigenous (30-33 degrees C) species and the response to acclimation differs
      among the two groups. The indigenous species show either a weak response to
      acclimation or ULT50 declines with increasing acclimation temperature, whereas in
      the invasive species ULT50 increases with acclimation temperature. These findings
      support the hypothesis that many invasive species will be favoured by climate
      change (warming and drying) at Marion Island. Moreover, manipulative field
      experiments have shown abundance changes in the indigenous and invasive
      springtail species in the direction predicted by the physiological data.

PMID- 17222863
TI  - Human herpes virus-8-encoded chemokine receptor homologues: novel mechanistic
      link for pulmonary arterial hypertension?

PMID- 17222864
TI  - Resveratrol: ready for prime time?

PMID- 17222865
TI  - A tightly packed hydrophobic cluster directs the formation of an off-pathway sub
      millisecond folding intermediate in the alpha subunit of tryptophan synthase, a
      TIM barrel protein.
AB  - Protein misfolding is now recognized as playing a crucial role in both normal and
      pathogenic folding reactions. An interesting example of misfolding at the
      earliest state of a natural folding reaction is provided by the alpha-subunit of
      tryptophan synthase, a (beta/alpha)(8) TIM barrel protein. The molecular basis
      for the formation of this off-pathway misfolded intermediate, I(BP), and a
      subsequent on-pathway intermediate, I1, was probed by mutational analysis of 20
      branched aliphatic side-chains distributed throughout the sequence. The
      elimination of I(BP) and the substantial destabilization of I1 by replacement of
      a selective set of the isoleucine, leucine or valine residues (ILV) with alanine
      in a large ILV cluster external-to-the-barrel and spanning the N and C termini
      (cluster 2) implies tight-packing at most sites in both intermediates.
      Differential effects on I(BP) and I1 for replacements in alpha3, beta4 and alpha8
      at the boundaries of cluster 2 suggest that their incorporation into I1 but not
      I(BP) reflects non-native folds at the edges of the crucial (beta/alpha)(1
      2)beta(3) core in I(BP). The retention of I(BP) and the smaller and consistent
      destabilization of both I(BP) and I1 by similar replacements in an internal-to
      the-barrel ILV cluster (cluster 1) and a second external-to-the-barrel ILV
      cluster (cluster 3) imply molten globule-like packing. The tight packing
      inferred, in part, for I(BP) or for all of I1 in cluster 2, but not in clusters 1
      and 3, may reflect the larger size of cluster 2 and/or the enhanced number of
      isoleucine, leucine and valine self-contacts in and between contiguous elements
      of secondary structure. Tightly packed ILV-dominated hydrophobic clusters could
      serve as an important driving force for the earliest events in the folding and
      misfolding of the TIM barrel and other members of the (beta/alpha)(n) class of
      proteins.

PMID- 17222867
TI  - The coiled-coil domain structure of the Sin Nombre virus nucleocapsid protein.
AB  - Hantaviruses can cause hemorrhagic fever with a renal syndrome and hantavirus
      pulmonary syndrome when transmitted to humans. The nucleocapsid protein of
      hantaviruses encapsidates viral genomic RNA and associates with transcription and
      replication complexes. Both the amino and carboxy termini of the nucleocapsid
      protein had been predicted to form trimers prior to the formation of the
      ribonucleoprotein. Crystal structures of amino-terminal fragments of the
      nucleocapsid protein showed the formation of intramolecular antiparallel coiled
      coils, but not intermolecular trimers. Thus, the amino-terminal part of the
      nucleocapsid protein is probably insufficient to initiate the trimerization of
      the full-length molecule.

PMID- 17222866
TI  - Relationships between the sequence of alpha-synuclein and its membrane affinity,
      fibrillization propensity, and yeast toxicity.
AB  - To investigate the alpha-synuclein protein and its role in Parkinson's disease,
      we screened a library of random point mutants both in vitro and in yeast to find
      variants in an unbiased way that could help us understand the sequence-phenotype
      relationship. We developed a rapid purification method that allowed us to screen
      59 synuclein mutants in vitro and discovered two double-point mutants that
      fibrillized slowly relative to wild-type, A30P, and A53T alpha-synucleins. The
      yeast toxicity of all of these proteins was measured, and we found no correlation
      with fibrillization rate, suggesting that fibrillization is not necessary for
      synuclein-induced yeast toxicity. We found that beta-synuclein was of
      intermediate toxicity to yeast, and gamma-synuclein was non-toxic. Co-expression
      of Parkinson's disease-related genes DJ-1, parkin, Pink1, UCH-L1, or synphilin,
      with synuclein, did not affect synuclein toxicity. A second screen, of several
      thousand library clones in yeast, identified 25 non-toxic alpha-synuclein
      sequence variants. Most of these contained a mutation to either proline or
      glutamic acid that caused a defect in membrane binding. We hypothesize that yeast
      toxicity is caused by synuclein binding directly to membranes at levels
      sufficient to non-specifically disrupt homeostasis.

PMID- 17222868
TI  - Mathematically modeling dynamics of T cell responses: predictions concerning the
      generation of memory cells.
AB  - Mathematical models of T cell population dynamics after infection typically
      assume that T cells differentiate according to a linear process in which they
      first become effector cells, and then after some time, differentiate further into
      memory cells. In this paper, we offer a different mathematical model which can
      equally well capture T cell dynamics, using data from lymphocytic
      choriomeningitis (LCMV) infection. Our model assumes that memory cells are
      intermediates that further differentiate into effector cells only from additional
      or stronger antigenic stimulation. Our assumption naturally leads to a testable
      prediction about the generation of T cell memory-that the memory phenotype of T
      cells should be present in detectable numbers during the expansion phase of the
      response. We use our model to estimate a rate of differentiation from memory type
      cells to effectors. We argue that this differentiation assumption, where memory
      cells are intermediates, captures recent experimental work on T cell
      differentiation, and hence this new mathematical model could be helpful in doing
      further studies of T cell population dynamics. We also propose a method of
      distinguishing the models by examining the ratio of memory T cells detectable
      long after an infection to the peak numbers of T cells at the end of the
      expansion phase.

PMID- 17222869
TI  - Loss or gain? Invasive aliens and biodiversity in the Mediterranean Sea.
AB  - More than 500 alien species were listed from the Mediterranean Sea. Though no
      extinction of a native species is known, sudden decline in abundance, and even
      local extirpations, concurrent with proliferation of aliens, had been recorded.
      Examination of the profound ecological impacts of some of the most conspicuous
      invasive alien species underscores their role, among multiple anthropogenic
      stressors, in altering the infralittoral communities. Local population losses and
      niche contraction of native species may not induce immediate extirpation, but
      they augur reduction of genetic diversity, loss of functions, processes, and
      habitat structure, increase the risk of decline and extinction, and lead to
      biotic homogenization. The relevant environmental policy and management framework
      is discussed.

PMID- 17222870
TI  - The toxicological impacts of oil and chemically dispersed oil: UV mediated
      phototoxicity and implications for environmental effects, statutory testing and
      response strategies.

PMID- 17222871
TI  - Impairment in writing, but not reading, morphologically complex words.
AB  - We report a patient, FP, with phonological dyslexia who is impaired in writing
      affixed words to dictation, but demonstrates no such deficit when reading affixed
      words. Moreover, she was much more impaired in the writing of regularly inflected
      words (e.g., "walked") as compared to irregularly inflected words (e.g., "ran")
      and derived words (e.g., "walker"). These findings indicate that FP's deficit was
      morphologically based and are consistent with accounts that assume that
      morphologically complex words are decomposed during lexical processing. The data
      also suggest that the lexical representations mediating reading and writing are,
      at least in part, dissociable.

PMID- 17222872
TI  - What are confabulators' memories made of? A study of subjective and objective
      measures of recollection in confabulation.
AB  - Confabulating patients claim to remember events that had not actually happened,
      suggesting a vivid subjective experience of false memories. The present study was
      aimed at examining the nature of subjective experience of retrieval in
      confabulators and its relation to the objective ability to recollect qualitative
      aspects of the original episode. In Experiment 1, 5 confabulators, 7 non
      confabulating patients, and 12 control subjects studied words under shallow and
      deep encoding conditions and underwent a Remember (R)/Know (K) recognition task
      [Tulving, E. (1985). Memory and consciousness. Canadian Psychology, 26, 1-12].
      For recognized words, they additionally indicated two qualitative features of the
      encoding context. Whereas subjective (i.e. R responses) and objective (i.e.
      source) measures of recollection were associated in normal controls and non
      confabulating patients, they were dissociated in confabulators. In Experiment 2,
      participants explained the content of their R responses. We found that
      confabulators' recollections mainly included autobiographical information related
      to test items, but not to the study encounter. We conclude that remembering
      states in confabulators may be linked to a deficit in inhibiting irrelevant
      memories triggered by test items during retrieval attempts.

PMID- 17222873
TI  - Broad screening of the legume family for variability in seed insecticidal
      activities and for the occurrence of the A1b-like knottin peptide entomotoxins.
AB  - Pea albumin 1b (PA1b) is a small sulphur-rich peptide from pea seeds, also named
      leginsulin because of the binding characteristics of its soybean orthologue. Its
      insecticidal properties were discovered more recently. By using a combination of
      molecular, biochemical and specific insect bioassays on seed extracts, we
      characterised genes from numerous Papilionoideae, but not from Caesalpinioideae
      or Mimosoideae, although the last group harboured species with partially positive
      cues (homologous biological activities). The A1b defence peptide family,
      therefore, appears to have evolved relatively late in the legume lineage, maybe
      from the sophoroid group (e.g. Styphnolobium japonicum). However, unambiguous
      sequence information is restricted to a group of tribes within the subfamily
      Papilionoideae (Psoraleae, Millettieae, Desmodieae, Hedysareae, Phaseoleae,
      Vicieae, and the now clearly polyphyletic "Trifolieae" and "Galegeae"). Recent
      diversification by gene duplications has occurred in many species, or longer ago
      in some lineages (Medicago truncatula), as well as probable gene or expression
      losses at different taxonomic levels (Loteae, Vigna subterranea).

PMID- 17222874
TI  - Expression of the sucrose binding protein from soybean: renaturation and
      stability of the recombinant protein.
AB  - The sucrose binding protein (SBP) belongs to the cupin family of proteins and is
      structurally related to vicilin-like storage proteins. In this investigation, a
      SBP isoform (GmSBP2/S64) was expressed in E. coli and large amounts of the
      protein accumulated in the insoluble fraction as inclusion bodies. The renatured
      protein was studied by circular dichroism (CD), intrinsic fluorescence, and
      binding of the hydrophobic probes ANS and Bis-ANS. The estimated content of
      secondary structure of the renatured protein was consistent with that obtained by
      theoretical modeling with a large predominance of beta-strand structure (42%)
      over the alpha-helix (9.9%). The fluorescence emission maximum of 303 nm for SBP2
      indicated that the fluorescent tryptophan was completely buried within a highly
      hydrophobic environment. We also measured the equilibrium dissociation constant
      (K(d)) of sucrose binding by fluorescence titration using the refolded protein.
      The low sucrose binding affinity (K(d)=2.79+/-0.22 mM) of the renatured protein
      was similar to that of the native protein purified from soybean seeds.
      Collectively, these results indicate that the folded structure of the renatured
      protein was similar to the native SBP protein. As a member of the bicupin family
      of proteins, which includes highly stable seed storage proteins, SBP2 was fairly
      stable at high temperatures. Likewise, it remained folded to a similar extent in
      the presence or absence of 7.6M urea or 6.7 M GdmHCl. The high stability of the
      renatured protein may be a reminiscent property of SBP from its evolutionary
      relatedness to the seed storage proteins.

PMID- 17222875
TI  - Rubella seroprevalence in an unvaccinated pregnant population in Malatya, Turkey.
AB  - BACKGROUND: Controlling congenital rubella by 2010 is one of the targets of the
      World Health Organization. Most European countries currently include rubella
      vaccine in their national immunization programmes, but not yet in Turkey.
      OBJECTIVES: To define rubella seroprevalence in pregnancy in Malatya, Turkey.
      STUDY DESIGN: A cross-sectional interview survey was conducted among pregnant
      women living in Malatya province from November 2003 to May 2004, together with a
      follow-up component. METHODS: Stratified probability proportional to size
      sampling methodology. A total of 824 pregnant women from 60 clusters were
      enrolled. After obtaining informed consent, participants' socio-demographic and
      fertility characteristics were collected by interview questionnaire. Various
      blood samples were drawn. After storing serum samples at -20 degrees C for 6
      months, anti-rubella IgM and IgG titres were studied by micro ELISA. Only 803
      sera were eligible for serological study. RESULTS: Of the 803 samples tested for
      rubella antibodies, 753 cases (93.8%) had anti-rubella IgG positivity, indicating
      past infection. Five of the pregnant women (0.6%) had both anti-rubella IgM and
      IgG positive results, suggesting a recent infection. The remaining 45 women
      (5.6%) were seronegative for both antibodies. Seroprevalence was not associated
      with age or urban/rural residency. All the five anti-rubella IgM positive women
      were in the second trimester of pregnancy. CONCLUSIONS: As 5.6% of pregnant women
      were susceptible to rubella during pregnancy, and five of them had already had a
      recent infection, immunization efforts should be directed at babies and
      adolescents.

PMID- 17222876
TI  - Higher mortality in areas of lower socioeconomic position measured by a single
      index of deprivation in Japan.
AB  - OBJECTIVES: To formulate an index representing area deprivation and elucidate the
      relation between the index and mortality in Japan. STUDY DESIGN: Ecological study
      for prefectures (N=47) and municipalities (N=3366) across Japan. METHODS: Based
      on socioeconomic indicators of seven domains of deprivation (i.e. unemployment,
      overcrowding, low social class and poverty, low education, no home ownership, low
      income and vulnerable group), an index was formulated using the z-scoring method.
      The relation between the index and mortality was examined by correlation
      analysis, hierarchical Poisson regression and comparison of standardized
      mortality ratio according to the index. RESULTS: The deprivation index ranged
      from -7.48 to 10.98 for prefectures and from -16.97 to 13.82 for municipalities.
      The index was significantly positively correlated with prefectural mortality,
      especially in the population aged under 74 years: r=0.65 for men and r=0.41 for
      women. At the municipal level, hierarchical Poisson regression showed a
      significant positive coefficient of the index to mortality for both men and
      women, and excess mortality in the most deprived fifth compared to the least
      deprived fifth was 26.4% in men and 11.8% in women. CONCLUSIONS: We formulated a
      deprivation index, which was substantially related to mortality at the
      prefectural and municipal levels. This study highlights the higher risk of dying
      among populations in socially disadvantaged areas and encourages the use of
      indices representing area socioeconomic conditions for further studies of area
      effects on health.

PMID- 17222877
TI  - Isolation and molecular characterization of a Brazilian strain of Borrelia
      anserina, the agent of fowl spirochaetosis.
AB  - Borrelia anserina the agent of fowl spirochaetosis, has a worldwide distribution,
      where it is transmitted by Argas spp. ticks. The present study reports the first
      molecular characterization and in vitro isolation of an avian spirochaete strain
      from Brazil, presumably identified as B. anserina originated from naturally
      infected Argas miniatus ticks. DNA fragments of the rrs and flab genes were
      amplified by PCR and sequenced to determine phylogenetic similarities. The
      resulting sequences were 99.8% (483 of 484) and 98.7% (754 of 764) similar to
      GenBank corresponding sequences of B. anserina rrs and flaB genes, respectively.
      By neighbor-joining phylogenetic analysis, the flaB sequence of the Brazilian
      strain clustered in a monophyletic group with the sequence of B. anserina under
      100% bootstrap support. The isolate was successfully isolated in BSK medium, with
      seven passages performed. The spirochaete strain isolated in the present study
      was genetically identified as B. anserina labeled as strain PL.

PMID- 17222878
TI  - Incidence of and risk factors for skin ailments among farmers working with
      wastewater-fed agriculture in Hanoi, Vietnam.
AB  - The use of wastewater in agriculture and aquaculture is widespread in many
      developing countries, but limited information is available about the health
      hazards associated with this practice. To study the occurrence of skin ailments
      in relation to wastewater use in agriculture and aquaculture, an open cohort of
      636 adults aged 15-70 years living in a wastewater-irrigated area in Hanoi,
      Vietnam, was followed by weekly visits for 12 months. A nested case-control study
      with 108 case/control pairs was conducted to investigate possible risk factors
      for skin ailments. The incidence rate of skin ailments was 32.5 episodes per 100
      person-years at risk. Independent determinants of skin ailments included
      wastewater contact in the past 7 days (odds ratio (OR=2.74, 95% confidence
      interval (CI) 1.29-5.82), female gender (OR=2.48, 95% CI 1.06-5.76), fish farming
      related jobs (OR=3.47, 95% CI 1.27-9.50) and lack of protective measures
      (OR=2.24, 95% CI 1.21-4.12). It is likely that effective promotion of personal
      protective measures and improved hygiene practices amongst wastewater users will
      mitigate the risk of dermatological problems and will thus be of benefit to
      public health in communities that rely on the use of wastewater for agricultural
      and aquacultural productions.

PMID- 17222879
TI  - On analytical approaches to epidemics on networks.
AB  - One way to describe the spread of an infection on a network is by approximating
      the network by a random graph. However, the usual way of constructing a random
      graph does not give any control over the number of triangles in the graph, while
      these triangles will naturally arise in many networks (e.g. in social networks).
      In this paper, random graphs with a given degree distribution and a given
      expected number of triangles are constructed. By using these random graphs we
      analyze the spread of two types of infection on a network: infections with a
      fixed infectious period and infections for which an infective individual will
      infect all of its susceptible neighbors or none. These two types of infection can
      be used to give upper and lower bounds for R(0), the probability of extinction
      and other measures of dynamics of infections with more general infectious
      periods.

PMID- 17222880
TI  - Analysis of the interaction of phytoestrogens and synthetic chemicals: an in
      vitro/in vivo comparison.
AB  - In the evaluation of chemical mixture toxicity, it is desirable to develop an
      evaluation paradigm which incorporates some critical attributes of real world
      exposures, particularly low dose levels, larger numbers of chemicals, and
      chemicals from synthetic and natural sources. This study evaluated the impact of
      low level exposure to a mixture of six synthetic chemicals (SC) under conditions
      of co-exposure to various levels of plant-derived phytoestrogen (PE) compounds.
      Estrogenic activity was evaluated using an in vitro human estrogen receptor (ER)
      transcriptional activation assay and an in vivo immature rat uterotrophic assay.
      Initially, dose-response curves were characterized for each of the six SCs
      (methoxyclor, o,p-DDT, octylphenol, bisphenol A, beta-hexachlorocyclohexane, 2,3
      bis(4-hydroxyphenyl)-propionitrile) in each of the assays. The six SCs were then
      combined at equipotent ratios and tested at 5-6 dose levels spanning from very
      low, sub-threshold levels, to a dose in which every chemical in the mixture was
      at its individual estrogenic response threshold. The SC mixtures also were tested
      in the absence or presence of 5-6 different levels of PEs, for a total of 36 (in
      vitro) or 25 (in vivo) treatment groups. Both in vitro and in vivo, low
      concentrations of the SC mixture failed to increase estrogenic responses relative
      to those induced by PEs alone. However, significant increases in response
      occurred when each chemical in the SC mixture was near or above its individual
      response threshold. In vitro, interactions between high-doses of SCs and PEs were
      greater than additive, whereas mixtures of SCs in the absence of PEs interacted
      in a less than additive fashion. In vivo, the SC and PE mixture responses were
      consistent with additivity. These data illustrate a novel approach for
      incorporating key attributes of real world exposures in chemical mixture toxicity
      assessments, and suggest that chemical mixture toxicity is likely to be of
      concern only when the mixture components are near or above their individual
      response thresholds. However, these data suggest that extrapolation from in vitro
      assays to in vivo mixture effects should be approached with caution.

PMID- 17222881
TI  - Alveolar macrophage cytokine response to air pollution particles: oxidant
      mechanisms.
AB  - Alveolar macrophages (AMs) primed with LPS and treated with concentrated ambient
      air particles (CAPs) showed enhanced release of tumor necrosis factor (TNF) and
      provide an in vitro model for the amplified effects of air pollution particles
      seen in people with preexisting lung disease. To investigate the mechanism(s) by
      which CAPs mediate TNF release in primed rat AMs, we first tested the effect of a
      panel of antioxidants. N-Acetyl-l-cysteine (20 mM), dimethyl thiourea (20 mM) and
      catalase (5 microM) significantly inhibited TNF release by primed AMs incubated
      with CAPs. Conversely, when LPS-primed AMs were treated with CAPs in the presence
      of exogenous oxidants (H(2)O(2) generated by glucose oxidase, 10 microM/h), TNF
      release and cell toxicity was significantly increased. The soluble fraction of
      CAPs suspensions caused most of the increased bioactivity in the presence of
      exogenous H(2)O(2). The metal chelator deferoxamine (DFO) strongly inhibited the
      interaction of the soluble fraction with H(2)O(2) but had no effect on the
      bioactivity of the insoluble CAPs fraction. We conclude that CAPs can mediate
      their effects in primed AMs by acting on oxidant-sensitive cytokine release in at
      least two distinct ways. In the primed cell, insoluble components of PM mediate
      enhanced TNF production that is H(2)O(2)-dependent (catalase-sensitive) yet
      independent of iron (DFO-insensitive). In the presence of exogenous H(2)O(2)
      released by AMs, PMNs, or other lung cells within an inflamed alveolar milieu,
      soluble iron released from air particles can also mediate cytokine release and
      cell toxicity.

PMID- 17222882
TI  - Active fragments of the antihemorrhagic protein HSF from serum of habu
      (Trimeresurus flavoviridis).
AB  - Certain snakes have antihemorrhagic proteins in their sera. Habu serum factor
      (HSF), an antihemorrhagic protein isolated from the serum of the Japanese habu
      snake (Trimeresurus flavoviridis) is composed of two cystatin-like domains (D1
      and D2) and a His-rich domain, and it inhibits several snake venom
      metalloproteinases (SVMPs). The activity of HSF can be abolished by
      trinitrophenylation of Lys residues with 2,4,6-trinitrobenzene sulphonic acid.
      Upon complex formation of HSF with SVMP, however, the loss of its inhibitory
      activity by the chemical modification was suppressed, and Lys(15), Lys(41), and
      Lys(103) residues in HSF were not trinitrophenylated. In order to identify the
      domain that is critical to the inhibitory activity on SVMPs, native HSF was
      digested with papain followed by cleavage with cyanogen bromide, yielding a low
      molecular mass fragment that was composed of two peptide chains (residues 5-89
      and 312-317) linked by a disulfide bond. This fragment inhibited several SVMPs
      and showed significant antihemorrhagic activity. This indicates that the N
      terminal half of D1 is indispensable for the antihemorrhagic activity of HSF.
      Furthermore, a three-dimensional model of two cystatin-like domains constructed
      by the homology modeling has indicated that three Lys residues (15, 41, and 103)
      are exposed to the same surface of HSF molecule.

PMID- 17222883
TI  - Binding and neutralization efficiencies of monoclonal antibodies, Fab fragments,
      and scFv specific for L1 epitopes on the capsid of infectious HPV particles.
AB  - We compared the neutralization abilities of individual monoclonal antibodies
      (MAb) of two large panels reactive with L1 epitopes of HPV-11 or HPV-16. Binding
      titers were compared using both L1-only VLPs and L1/L2 pseudovirions. While the
      VLPs were antigenically similar to the pseudovirions, clear differences in the
      surface exposure of some epitopes were evident with the HPV-16 particles. To
      determine whether all antibody binding events are equivalent in their
      neutralizing effect on infectious HPV virions or pseudovirions, the binding and
      neutralization titers for individual MAbs were used to calculate the relative
      neutralization efficiency for each antibody. HPV neutralization was achieved by
      all MAbs capable of strong binding to either linear or conformation-sensitive
      epitopes on pseudovirus particles. Our data suggest, however, that some L1
      epitopes may be more neutralization-sensitive than other surface epitopes, in
      that successful infection can be blocked by varying degrees of epitope
      saturation. Additionally, the effective neutralization of virions by several
      monovalent Fab fragments and single-chain variable fragments (scFv) demonstrates
      that viral neutralization does not require HPV particle aggregation or L1
      crosslinking. Identification of capsid protein structures rich in neutralization
      sensitive epitopes may aid in the development of improved recombinant vaccines
      capable of eliciting effective and long-term antibody-mediated protection against
      multiple HPV types.

PMID- 17222885
TI  - The effect of inoculum on the performance of sulfate-reducing columns treating
      heavy metal contaminated water.
AB  - Sulfate-reducing permeable reactive zones (SR-PRZs) are a passive means of
      immobilizing metals and neutralizing the pH of mine drainage through microbially
      mediated reactions. In this bench-scale study, the influence of inoculum on the
      performance of columns simulating SR-PRZs was investigated using chemical and
      biomolecular analyses. Columns inoculated from two sources (bovine dairy manure
      (DM) and a previous sulfate-reducing column (SRC)) and uninoculated columns (U)
      were fed a simulated mine drainage and compared on the basis of pH neutralization
      and removal of cadmium, zinc, iron, and sulfate. Cadmium, zinc, and sulfate
      removal was significantly higher in SRC columns than in the DM and U columns,
      while there was no significant difference between the DM and U columns.
      Denaturing gradient gel electrophoresis (DGGE) analysis revealed differences in
      the microbial community composition among columns with different inocula, and
      indicated that the microbial community in the SRC columns was the first to reach
      a pseudo-steady state. In the SRC columns, a higher proportion of the DGGE band
      DNA sequences were related to microorganisms that carry out cellulose
      degradation, the rate-limiting step in SR-PRZ energy flow, than was the case in
      the other columns. The proportion of sulfate-reducing bacteria of the genus
      Desulfobacterium was monitored using real-time quantitative PCR and was observed
      to be consistently higher in the SRC columns. The results of this study suggest
      that the inoculum plays an important role in SR-PRZ performance. This is the
      first report providing a detailed analysis of the effect of different microbial
      inocula on the remediation of acid mine drainage.

PMID- 17222884
TI  - Membrane topology of murine coronavirus replicase nonstructural protein 3.
AB  - Mouse hepatitis virus (MHV) is a member of the family Coronaviridae. These
      positive strand RNA viruses encode a replicase polyprotein that is processed into
      16 nonstructural proteins (nsps). The nsps assemble with membranes to generate
      double membrane vesicles, which are the sites of viral RNA synthesis. MHV nsp3
      contains multiple domains including two papain-like protease domains, PLP1 and
      PLP2, and a predicted transmembrane (TM) domain. In this study, we determined the
      membrane topology of nsp3-TM and showed that TM-mediated tethering of PLP2 is
      important for processing at cleavage site 3. Biochemical analysis revealed that
      nsp3 is an integral membrane protein that is inserted into the endoplasmic
      reticulum (ER) membranes co-translationally and glycosylated at asparagine-2357.
      Proteinase K digestion experiments indicate that the TM domain of nsp3 has 4
      membrane-spanning helices. We show that nsp3-TM is sufficient in mediating ER
      membrane association of a cytosolic protein. This study is the first detailed
      analysis of the topology and function of the coronavirus nsp3 TM domain.

PMID- 17222886
TI  - Reaction pathways and kinetics of butylated hydroxyanisole with UV, ozonation,
      and UV/O(3) processes.
AB  - The chemical degradation of the endocrine disrupting chemical, butylated
      hydroxyanisole (BHA), was investigated by different treatment processes including
      ultraviolet (UV) irradiation, ozonation (O(3)), and UV/O(3). O demethylation,
      dimerization, and oxidation have been found to be the main degradation
      mechanisms. A systematic decay pathway was proposed based on ten identified
      intermediates in the studied processes, including a unique pathway leading to the
      formation of precipitates in the ozonation process. An unconventional minimum
      type variation of BHA decay rate constants from acidic to caustic range has been
      found for both ozonation and UV/O(3) processes. The precipitates formed during
      ozonation can be removed during the process to optimize the treatment, while the
      UV/O(3) process can offer a relatively fast and clean process to degrade BHA and
      its associated intermediates.

PMID- 17222887
TI  - Evaluation of enrichment-free PCR-based detection on the rfbE gene of Escherichia
      coli O157--application to municipal wastewater.
AB  - Escherichia coli O157 strains have emerged as important human enteric pathogens.
      Strains that express the O-antigen 157 are commonly associated with severe
      clinical manifestations, including bloody diarrhea, hemorrhagic colitis, and
      hemolytic uremic syndrome. E. coli O157 strains may be transmitted in a variety
      of ways, including food, water and person-to-person or animal-to-person contact.
      Fecal contamination is one source of environmental contamination and is
      responsible for the presence of these pathogens in the environment. We used a
      specific and sensitive PCR assay based on the rfbE gene to detect low levels of
      these pathogens in wastewater. The set of primers used was designed to amplify an
      intragenic segment of the rfbE gene. The amplification assay detected 200 CFU of
      E. coli O157 in pure water. The prevalence of E. coli O157 in the effluents of 44
      wastewater treatment plants was determined (7%).

PMID- 17222889
TI  - Chemical contaminants in fish feeds used in federal salmonid hatcheries in the
      USA.
AB  - Recent studies have demonstrated that fish feeds contain significant
      concentrations of contaminants, many of which can bioaccumulate and
      bioconcentrate in fish. Organochlorine (OC) contaminants are present in the fish
      oils and fish meals used in feed manufacture, and some researchers speculate that
      all fish feeds contain measurable levels of some contaminants. To determine the
      concentration of contaminants in feeds used in US Fish and Wildlife Service's
      National Fish Hatcheries, we systematically collected samples of feed from 11
      cold-water fish hatcheries. All samples (collected from October 2001 to October
      2003) contained at least one polychlorinated dibenzo-p-dioxin (PCDD),
      polychlorinated dibenzofuran (PCDF), polychlorinated biphenyl (PCB) congener, or
      dichlorodiphenyltrichloroethane (DDT) metabolite. Of the 55 samples in which they
      were analyzed 39 contained PCDDs, 24 contained PCDFs and 24 contained DDT or its
      metabolites. There were 10- to 150-fold differences in concentrations of total
      PCBs, PCDDs, PCDFs and DDT. Although PCBs were the most commonly detected
      contaminant in our study, concentrations (range: 0.07-10.46 ng g(-1) wet weight)
      were low compared to those reported previously. In general, we also found lower
      levels of OCs than reported previously in fish feed. Perhaps most notable was the
      near absence of OC pesticides - except for DDT or its metabolites, and two
      samples containing hexachlorocyclohexane (HCH). While contaminant concentrations
      were generally low, the ecological impacts can not be determined without a
      measure of the bioaccumulation of these compounds in the fish and the fate of
      these compounds after the fish are released.

PMID- 17222890
TI  - Membrane introduction/laser photoionization time-of-flight mass spectrometry.
AB  - Two-photon resonance enhanced multiphoton ionization (REMPI) has been shown to be
      a unique ionization method for mass spectrometry, exhibiting both high
      sensitivity and chemical selectivity. Because REMPI is a gas-phase method, its
      applications have been limited either to direct analysis of vapor phase samples,
      or in conjunction with an initial laser desorption or other vaporization step. We
      describe here for the first time a combination of membrane introduction mass
      spectrometry (MIMS) and REMPI with time-of-flight mass spectrometry (TOF-MS),
      which allows for the direct analysis of trace amounts of organic compounds in
      water samples. The objective of our research was the detection of very low levels
      of aromatic contaminants, particularly benzene, toluene, and xylene (BTX), in
      aqueous solutions without interference due to the water. We have measured limits
      of detection (LOD) for selected aromatics in water below 1 part-per-trillion with
      an averaging time of less than 10 s using a continuous sample flow.

PMID- 17222891
TI  - Effect of oversulfated dermatan sulfate derivatives on platelet aggregation.
AB  - We have investigated the effect on human platelet aggregation of native dermatan
      sulfate (DS) and three oversulfated DS derivatives with different sulfur
      contents, and compared it with that of unfractionated heparin. An inhibitory
      effect on collagen-induced platelet aggregation was observed only with
      unfractionated heparin at high concentrations, whereas no inhibitory effect was
      observed when arachidonic acid was used. Heparin was the most potent inhibitor of
      the thrombin-induced platelet aggregation in platelet-rich plasma (PRP), whereas
      the oversulfated DS had a higher potency than the native DS. All these
      glycosaminoglycans (GAGs) also inhibited thrombin-induced aggregation of washed
      platelets in the presence of antithrombin (AT) or heparin cofactor II (HCII) but
      not in their absence. Heparin was by far the most potent inhibitor of washed
      platelet aggregation in the presence of AT, whereas the inhibitory effects of the
      DS (native or oversulfated) were lower but dependent on the sulfur content. In
      the presence of HCII, DSb, a slightly oversulfated DS, had the highest inhibitory
      effect, whereas heparin and DSd, the most oversulfated derivative, had lower
      potencies in this case. These data suggest that the inhibition of thrombin
      induced platelet aggregation by the oversulfated DS derivatives is related to
      their ability to potentiate thrombin inactivation by AT or HCII. Hence, the
      oversulfated DS derivatives may not have an effect per se on the inhibition of
      platelet aggregation. They may constitute a new class of anticoagulants with
      enhanced anticoagulant effects in comparison with the native DS, but with only
      minor side-effects of bleeding in comparison with heparin.

PMID- 17222892
TI  - Efficient targeted anticoagulant with active RGD motif.
AB  - Three anticoagulants combining large peptide recombinant hirudin variants (rHV2
      K47) and Arg-Gly-Asp (RGD) motif related to platelet aggregation were generated,
      i.e. sequences CRFPRGDADPYCE and CNPRGDFRCI were added to the C-terminus of
      hirudin to obtain RGD-hirudin 1 and 2, respectively, and the sequence RGDSE was
      inserted between residues 53-54 of hirudin to obtain RGD-hirudin 3. All products
      exhibited antithrombin and antiplatelet activities, especially IC50 of RGD
      hirudin 1 and 2 were much lower with respect to previously reported similar
      peptides. Our data suggested that RGD-hirudin 1 and 2 would be promising
      anticoagulants in clinic. Moreover, the triangular structure of active RGD was
      shown by computer simulation, which might contribute to our understanding on
      integrin-related peptides and proteins.

PMID- 17222893
TI  - Primary peritoneal serous psammocarcinoma with recurrent disease and metastasis:
      a case report and review of the literature.
AB  - BACKGROUND: Psammocarcinoma is a rare variant of serous carcinoma arising from
      either ovary or peritoneum. Although behavior of tumor is uncertain, it has been
      suggested to be similar to serous carcinomas of low malignant potential. CASE: A
      67-year-old woman was admitted with an abnormal vaginal bleeding and abdomino
      pelvic pain. Computed tomography showed a heavily calcified rectovaginal mass
      that was histologically characterized by numerous psammoma bodies and low-grade
      cytological features. Following the primary surgery, the patient received 9
      cycles of chemotherapy. Five years later, she presented with diffuse recurrence
      and 1 year later, with metastasis to the vertebra. CONCLUSION: Although
      psammocarcinoma is known to behave in a more indolent course, clinicians should
      be aware that patients with this disease may have a clinically aggressive,
      recurrent, and metastatic tumor that necessitated systemic therapy.

PMID- 17222894
TI  - Sentinel lymph node biopsy improves staging in early cervical cancer.
AB  - OBJECTIVES: The main study objective was to describe the distribution of sentinel
      lymph nodes (SLNs) and the prevalence of SLN micrometastases in patients with
      early cervical cancer. The secondary objective was to confirm the SLN detection
      rate and negative predictive value found in our preliminary study. PATIENTS AND
      METHODS: We prospectively included 25 patients with early cervical cancer, each
      of whom received an injection of 120 MBq of technetium-99m for preoperative
      lymphoscintigraphy and intraoperative node detection using an endoscopic gamma
      probe. Patent blue dye was injected intraoperatively. SLNs were sought in the
      pelvic and para-aortic drainage areas. Radical iliac dissection was performed
      routinely at the end of the procedure. SLNs were examined after hematoxylin-eosin
      saffron staining; negative specimens were assessed using immunohistochemistry.
      RESULTS: Most (85%) of the SLNs were in the inter-iliac territory. Para-aortic or
      parametrial SLNs were found respectively in 2 patients and common iliac SLNs in 5
      patients. Thus 9/25 patients had additional information due to SLN detection. One
      metastasis and one micrometastasis were detected in SLNs. No patients had
      positive non-sentinel nodes with negative SLNs. CONCLUSION: SLN detection ensures
      the identification of SLNs in unusual locations in 36% of patients. SLN disease
      was found in 8% of our patients. Thus, SLN biopsy improves staging in patients
      with early cervical cancer. Studies in larger patient populations are needed to
      evaluate the clinical impact of SLN biopsy.

PMID- 17222895
TI  - Adolescent cortical development: a critical period of vulnerability for
      addiction.
AB  - Cortical growth and remodeling continues from birth through youth and adolescence
      to stable adult levels changing slowly into senescence. There are critical
      periods of cortical development when specific experiences drive major synaptic
      rearrangements and learning that only occur during the critical period. For
      example, visual cortex is characterized by a critical period of plasticity
      involved in establishing visual acuity. Adolescence is defined by characteristic
      behaviors that include high levels of risk taking, exploration, novelty and
      sensation seeking, social interaction and play behaviors. In addition,
      adolescence is the final period of development of the adult during which talents,
      reasoning and complex adult behaviors mature. This maturation of behaviors
      corresponds with periods of marked changes in neurogenesis, cortical synaptic
      remodeling, neurotransmitter receptors and transporters, as well as major changes
      in hormones. Frontal cortical development is later in adolescence and likely
      contributes to refinement of reasoning, goal and priority setting, impulse
      control and evaluating long and short term rewards. Adolescent humans have high
      levels of binge drinking and experimentation with other drugs. This review
      presents findings supporting adolescence as a critical period of cortical
      development important for establishing life long adult characteristics that are
      disrupted by alcohol and drug use.

PMID- 17222896
TI  - Neighbourhood food environment and diet: time for improved conceptual models?

PMID- 17222897
TI  - How iconic gestures enhance communication: an ERP study.
AB  - EEG was recorded as adults watched short segments of spontaneous discourse in
      which the speaker's gestures and utterances contained complementary information.
      Videos were followed by one of four types of picture probes: cross-modal related
      probes were congruent with both speech and gestures; speech-only related probes
      were congruent with information in the speech, but not the gesture; and two sorts
      of unrelated probes were created by pairing each related probe with a different
      discourse prime. Event-related potentials (ERPs) elicited by picture probes were
      measured within the time windows of the N300 (250-350 ms post-stimulus) and N400
      (350-550 ms post-stimulus). Cross-modal related probes elicited smaller N300 and
      N400 than speech-only related ones, indicating that pictures were easier to
      interpret when they corresponded with gestures. N300 and N400 effects were not
      due to differences in the visual complexity of each probe type, since the same
      cross-modal and speech-only picture probes elicited N300 and N400 with similar
      amplitudes when they appeared as unrelated items. These findings extend previous
      research on gesture comprehension by revealing how iconic co-speech gestures
      modulate conceptualization, enabling listeners to better represent visuo-spatial
      aspects of the speaker's meaning.

PMID- 17222898
TI  - Evaluation of bond strength of soft relining materials to denture base polymers.
AB  - OBJECTIVES: To evaluate the initial bonding properties of recently and previously
      introduced soft relining materials to denture base polymers with different
      polymerization techniques and different water content. METHODS: The initial
      tensile bond strength of 10 soft liners (Mollosil Plus, Dentusil, Ufi gel Soft,
      GC Reline Soft, Silagum Comfort, Vertex Soft, Astron Soft, Molloplast B,
      Flexacryl Soft, Triad Resiline) to three denture base polymers (Paladon 65,
      Palapress Vario, Ivocap Plus) were assessed with a modified method. Paladon 65
      specimens immersed in water for 3 months were also used to test the effect of
      water content of denture base polymer on bond strength results. After testing, a
      visual examination of the fracture surfaces and a SEM investigation of the
      interface structure were performed. Tensile strength of each soft liner material
      was also tested. Data were analyzed statistically by two-way ANOVA (alpha =
      0.05). RESULTS: Significant differences were found among tensile bond strength
      results (P < 0.05). Vinyl poly(organosiloxane) soft liners (Mollosil Plus,
      Dentusil, Ufi gel Soft, GC Reline Soft, Silagum Comfort) and a plasticized PMMA
      soft liner (Vertex Soft) gave statistically similar bond strength results for
      different denture base polymers (P>0.05). For the other materials used (Astron
      Soft, Molloplast B, Flexacryl Soft, Triad Resiline), different denture base
      polymers caused significantly different results (P < 0.05). Poly(organosiloxane)
      based materials gave slightly higher bond strength results with water immersed
      specimens than with the dry specimens. SIGNIFICANCE: A wide variety of newly
      formulated soft liners used in this study gave comparable or better bond strength
      results compared to Molloplast B.

PMID- 17222899
TI  - Activity-based identity experiences and their relations to problem behavior and
      psychological well-being in adolescence.
AB  - The current study explored the associations between activity-based identity
      experiences and youth outcomes. Participants were 107 high school students and
      one parent or guardian of each from three communities in a Northeastern state.
      Youth completed a measure of activity-based identity experiences (Personally
      Expressive Activities Questionnaire (PEAQ) [Waterman, A. S. (1990). Personal
      expressiveness: Philosophical and psychological foundations. Journal of Mind and
      Behavior, 11, 47-74]), as well as measures of psychological well-being, substance
      use, and delinquency. Parents completed the Child Behavior Checklist [Achenbach,
      T. M. (1991). Manual for the Child Behavior Checklist/4-18 and 1991 profile.
      Burlington, VT: University of Vermont Department of Psychiatry]. Together, three
      identity experiences derived from the PEAQ, personal expressiveness, goal
      directed behavior, and flow, were significant predictors of adolescent-reported
      delinquency and well-being. Goal-directed behavior also uniquely predicted
      adolescent-reported delinquency and well-being. Suggestions for future research
      and potential implications for intervention are discussed.

PMID- 17222900
TI  - Reactions to dating violence among Latino teenagers: an experiment utilizing the
      Articulated Thoughts in Simulated Situations paradigm.
AB  - Dating violence is a serious problem among adolescents and young adults.
      Understanding teens' reactions to dating violence offers the potential to
      understand the factors that lead to perpetration of violent behavior and to
      elucidate prevention strategies. Knowledge concerning youth attitudes about
      dating violence is limited, and has largely come from self-report questionnaires
      to date. We utilized the Articulated Thoughts in Simulated Situations (ATSS)
      paradigm to assessing Latino teens' reactions to dating violence. Forty-one 9th
      grade students were presented with four simulated dating violence scenarios, and
      articulated their thoughts in response to them. Teens' reactions to dating
      violence differed on a variety of dimensions as a function of their gender, the
      gender of the perpetrator, and familiarity with the perpetrator.

PMID- 17222901
TI  - High hydrostatic pressure approach proves RNA catalytic activity without
      magnesium.
AB  - High hydrostatic pressure (HHP) technique was used to evaluate a mechanism of RNA
      hydrolysis with RNA. We showed that hammerhead ribozyme specifically cleaves RNA
      substrate at HHP in the absence of Mg(2+). A deoxyribozyme "10-23" was active in
      the same conditions. These results pointed out that the hydrolytic activity of
      nucleic acid depends on proper tertiary structure of a complex with a substrate.
      They prove that magnesium ion is not directly involved in catalysis process. On
      that basis we show the mechanism of RNA hydrolysis catalyzed with nucleic acids
      at HHP.

PMID- 17222902
TI  - Synthesis of cholesterol imprinted polymeric particles.
AB  - The aim of this study is to prepare cholesterol-imprinted polymeric particles. N
      Methacryloyl-(L)-tyrosinemethylester (MAT) was chosen as the complexing monomer.
      In the first step, functional monomer MAT was synthesized by the reaction of L
      tyrosine methylester and methacryloyl chloride and characterized by FTIR and NMR.
      Then, cholesterol was complexed with MAT in different mol ratios and the
      cholesterol-imprinted poly(2-hydroxyethyl methacrylate-N-methacryloyl-(L)
      tyrosine methylester) [MIP] particles were synthesized by bulk polymerization.
      After that, the template molecules (i.e., cholesterol) were removed using
      chloroform. MIP particles were characterized by elemental analysis, FTIR, SEM,
      swelling tests and surface area measurements. Cholesterol adsorption experiments
      were performed in a batch experimental set-up. Adsorption medium was methanol or
      intestinal mimicking solution. Stigmasterol and estradiol were used as competing
      molecules in selectivity tests. Obtained results were as follows: swelling ratio
      of MIP and non-imprinted (NIP) particles were 60.8% and 44.1% in water. With the
      increase in the amount of MAT in the polymerization medium, incorporation of MAT
      was increased (16.6-78.0 micromol/g). SEM photographs showed the surface
      roughness and porosity. Specific surface area of NIP and MIP particles were found
      as 19.2 and 31.5 m(2)/g, respectively. Template molecules (i.e., cholesterol)
      were removed from the polymer structure in the ratio of 76-84% of the initial
      concentration. Cholesterol adsorption increased with the increase in cholesterol
      concentration up to 1.5 mg/mL. MIP particles prepared using higher amounts of
      cholesterol exhibit significantly higher capacity to the NIP particles (i.e.,
      control polymer). MIP particles were 3.09 and 3.60 times selective with respect
      to the stigmasterol and estradiol, respectively. Reusability of MIP particles was
      also investigated. MIP particles showed negligible loss in the cholesterol
      adsorption capacity after five adsorption-desorption cycles with the same
      adsorbent.

PMID- 17222903
TI  - Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord
      neurons.
AB  - This paper describes the evaluation of the auto-catalytic anti-oxidant behavior
      and biocompatibility of cerium oxide nanoparticles for applications in spinal
      cord repair and other diseases of the central nervous system. The application of
      a single dose of nano-ceria at a nano-molar concentration is biocompatible,
      regenerative and provides a significant neuroprotective effect on adult rat
      spinal cord neurons. Retention of neuronal function is demonstrated from
      electrophysiological recordings and the possibility of its application to prevent
      ischemic insult is suggested from an oxidative injury assay. A mechanism is
      proposed to explain the auto-catalytic properties of these nanoparticles.

PMID- 17222904
TI  - Oxidative stress and the induction of cyclooxygenase enzymes and apoptosis in the
      murine placenta.
AB  - Placental oxidative stress has been implicated in many complications of human
      pregnancy, including preterm delivery and preeclampsia. It is now appreciated
      that reactive oxygen species can induce a spectrum of changes, ranging from
      homeostatic induction of enzymes to apoptotic cell death. Little is known
      regarding the occurrence of placental oxidative stress in other species. We
      investigated markers of oxidative stress in the labyrinthine (LZ) and junctional
      (JZ) zones of the murine placenta across gestational age, and correlated these
      with expression of the cyclooxygenase enzymes COX-1 and COX-2, and apoptosis. We
      tested a causal link between the two by subjecting placental explants to hypoxia
      reoxygenation (H/R) in vitro, a known stimulus for generation of oxidative
      stress. Western blotting demonstrated significant increases in the concentrations
      of hydroxynonenal (HNE), COX-1 and COX-2 with gestational age. Dual-labelling
      demonstrated co-localisation of HNE, and COX-1 and COX-2 within the trophoblast
      of the LZ, and glycogen cells of the JZ. An apoptotic index based on TUNEL
      positivity demonstrated an increase with gestational age, and dual-labelling
      showed co-localisation of TUNEL labelling with HNE and active caspase-3 within
      the trophoblast of the LZ. H/R significantly increased oxidative stress,
      induction of COX-1 and COX-2, and the apoptotic index. Co-localisation
      demonstrated the increases in COX to be within the trophoblast of the LZ, and in
      particular the glycogen cells of the JZ. Apoptosis was restricted to the LZ. We
      speculate that the induction of COX enzymes is a physiological response to
      oxidative stress, and may play a role in initiating or augmenting parturition.
      Generation of oxidative stress may also play a role in influencing the growth
      trajectory of the placenta, and its component cell types. The mouse may provide
      an experimental genetic model in which to investigate these phenomena.

PMID- 17222905
TI  - The involvement of the central cholinergic system in the pressor and bradycardic
      effects of centrally administrated melittin in normotensive conscious rats.
AB  - Recently we demonstrated that centrally administrated melittin, a phospholipase
      A(2) (PLA(2)) activator, caused pressor and bradycardic effect in the
      normotensive conscious rats. In the current study we aimed to determine the
      mediation of central cholinergic system in the pressor and bradycardic effect of
      centrally administrated melittin. Studies were performed in normotensive male
      Sprague-Dawley rats. 1.5, 3.0 or 6.0microg/5.0microl doses of melittin were
      injected intracerebroventricularly (i.c.v.). Melittin caused dose- and time
      dependent increases in mean arterial pressure (MAP) and decrease in heart rate
      (HR). In order to test the mediation of central cholinergic system on the pressor
      and bradycardic effect of melittin, the rats were pretreated with mecamylamine
      (50microg; i.c.v.), cholinergic nonselective nicotinic receptor antagonist,
      atropine sulfate (10microg; i.c.v.), a cholinergic nonselective muscarinic
      receptor antagonist, hemicholinium-3 (20microg; i.c.v.), a high affinity neuronal
      choline uptake inhibitor, methyllycaconitine (10 and 25microg; i.c.v.) or alpha
      bungarotoxin (10 and 25microg; i.c.v.), selective antagonists of alpha-7 subtype
      nicotinic acetylcholine receptors (alpha7nAChRs), 15min prior to melittin
      (3.0microg) injection. Pretreatment with mecamylamine, hemicholinium-3,
      methyllycaconitine or alpha-bungarotoxin partially attenuated the pressor and
      bradicardia effect of elicited by melittin in the normotensive conscious rats
      whereas pretreatment with atropine had no effect. In conclusion, i.c.v.
      administration of melittin increases MAP and decreases HR in conscious rats. The
      activation of central nicotinic cholinergic receptors, predominantly
      alpha7nAChRs, partially acts as a mediator in the pressor responses to i.c.v.
      injection of melittin in the normotensive conscious rats. Moreover, decreased
      uptake of choline to the cholinergic terminals may consider that melittin
      activates central choline and acetylcholine release, as well.

PMID- 17222906
TI  - The GAP-related domain of neurofibromin attenuates proliferation and
      downregulates N- and K-Ras activation in Nf1-negative AML cells.
AB  - Inactivation of the NF1 tumor suppressor causes myeloproliferative diseases. NF1
      encodes a GTPase activating protein (GAP) for Ras. Myeloid cells with loss of NF1
      have high levels of Ras-GTP, functionally equivalent to the effects of RAS
      oncogenes. We investigated the effects of the NF1 GAP-related domain (GRD) in
      proliferation, apoptosis and Ras-GTP levels in Nf1-negative acute myeloid
      leukemia (AML) cells. In AML cells, with cooperating mutations, the expression of
      the neurofibromin GRD causes significant reductions of N- and K-Ras-GTP levels,
      which is not incompatible with AML cell survival, but which is strongly selected
      against due to suppression of proliferation.

PMID- 17222907
TI  - Fish cast NETs: neutrophil extracellular traps are released from fish
      neutrophils.
AB  - Neutrophil extracellular traps (NETs), which are extracellular DNA structures
      released from neutrophils, are described and characterized for the first time in
      fish using fluorescent confocal microscopy. Confocal images of fish neutrophil
      suspensions stained with 6'-diamino-2-phenylindole, dihydrochloride DNA
      fluorescent stain (DAPI) revealed the presence of NETs which appeared as fibrous
      structures connecting several cells. Co-localization of NETs with neutrophil
      granular proteins and actin was investigated using specific antibodies and
      probes. Double staining of neutrophils with SYTOX green and DAPI revealed that
      SYTOX stain applied to living cells stained extracellular DNA, but not nuclei.
      NETs are actively released from stimulated living cells, associated with granular
      proteins, but not with cytoskeleton, and are not a product of nuclear degradation
      seen in late apoptotic stages. Additionally, a fluorometric microtiter plate
      assay to quantify the release of NETs was adopted for use with fish neutrophils,
      and the effect of stress on NETs release was studied. This assay detected the
      inhibition of DNA release during stress conditions. In summary, NETs were
      released from living fish kidney neutrophils upon stimulation, characterized
      using fluorescence DNA-binding dyes, specific antibodies and probes, and
      quantified using a microtiter plate fluorometric assay that can rapidly measure a
      large number of samples. Detection of NETs can be used as an additional assay to
      an existing battery of functional tests, and as a new research model to study the
      effects of stress, immunomodulators, and diseases.

PMID- 17222908
TI  - Glutathione S-transferase cytosolic isoform in the pink-shrimp, Farfantepenaeus
      brasiliensis, from Conceicao Lagoon, Santa Catarina Island, SC, Brazil.
AB  - Contaminant input into the environment can affect the biochemical responses of
      exposed organisms. Activity of conjugation enzymes, such as glutathione S
      transferase (GST) has been proposed as a biomarker of susceptibility to the
      presence of potentially damaging xenobiotics. The aim of the present study was to
      evaluate the activity of total and Pi-class GST in the hepatopancreas of pink
      shrimp Farfantepenaeus brasiliensis. The shrimp were caught at a single site at
      Conceicao Lagoon and transplanted to another site (Canto da Lagoa - CA) in the
      same lagoon, and to the laboratory (LAB), where they were kept for 15 days. This
      experiment was carried out in winter 2003 and in summer 2004. Shrimp were sampled
      before the exposure, at a zero time (t0), and after 15-days at CA site and LAB.
      The activity of total GST and Pi-isoform were analyzed using CDNB and ethacrynic
      acid (EA) as substrates, respectively. Shrimp caught in winter showed higher
      levels of Pi-class GST than those caught in summer, for both t0 and CA groups.
      Moreover, differences in the activity of this GST isoform between groups were
      observed only in winter, where the animals from t0 and CA groups presented higher
      activity when compared to those kept in the laboratory. This difference could be
      associated either to changes in the contaminant input or to other water quality
      parameters in this ecosystem. The elevated GST Pi activity observed in the shrimp
      of both t0 and CA groups sampled in winter could be related to salinity, since it
      was higher in winter than in summer. We could also suggest a possible association
      of this finding to a seasonal metabolic variation in this penaeid. If that is the
      case, one should take into account these alterations when considering the use of
      this GST isoform as biomarker in F. brasiliensis in environmental monitoring
      programs.

PMID- 17222909
TI  - Antibodies to the superantigenic site of HIV-1 gp120: hydrolytic and binding
      activities of the light chain subunit.
AB  - Antibodies (Abs) to the superantigenic determinant of HIV gp120 (gp120(SAg)) are
      potential protective agents against HIV infection. We report that the light chain
      subunits of Abs cloned from lupus patients using phage library methods bind and
      hydrolyze gp120(SAg) independent of the heavy chain. Unlike frequent gp120(SAg)
      recognition by intact Abs attributable to V(H) domain structural elements, the
      isolated light chains expressed this activity rarely. Four light chains capable
      of gp120(SAg) recognition were identified by fractionating phage displayed light
      chains using peptide probes containing gp120 residues 421-433, a gp120(SAg)
      component. Three light chains expressed non-covalent gp120(SAg) binding and one
      expressed gp120(SAg) hydrolyzing activity. The hydrolytic light chain was
      isolated by covalent phage fractionation using an electrophilic analog of
      residues 421-433. This light chain hydrolyzed a reporter gp120(SAg) substrate and
      full-length gp120. Other peptide substrates and proteins were hydrolyzed at lower
      rates or not at all. Consistent with the expected nucleophilic mechanism of
      hydrolysis, the light chain reacted selectively and covalently with the
      electrophilic gp120(SAg) peptide analog. The hydrolytic reaction entailed a fast
      initial step followed by a slower rate limiting step, suggesting rapid substrate
      acylation and slow deacylation. All four gp120(SAg)-recognizing light chains
      contained sequence diversifications relative to their germline gene counterparts.
      These observations indicate that in rare instances, the light chain subunit can
      bind and hydrolyze gp120(SAg) without the participation of the heavy chain. The
      pairing of such light chains with heavy chains capable of gp120(SAg) recognition
      represents a potential mechanism for generating protective Abs with enhanced HIV
      binding strength and anti-viral proteolytic activity.

PMID- 17222910
TI  - Differential effects of selenium compounds on glucose synthesis in rabbit kidney
      cortex tubules and hepatocytes. In vitro and in vivo studies.
AB  - Although selenium is taken with diet mainly as selenoamino acids, its
      hypoglycaemic action on hepatic gluconeogenesis has been studied with the use of
      inorganic selenium derivatives. The aim of the present investigation was to
      compare relative efficacies of inorganic and organic selenium compounds in
      reducing glucose synthesis in hepatocytes and renal tubules, significantly
      contributing to the glucose homeostasis. In contrast to hepatocytes, both
      selenite and methylselenocysteine inhibited renal gluconeogenesis by about 40-45%
      in control rabbits. Selenate did not affect this process, whereas
      selenomethionine inhibited gluconeogenesis by about 20% in both hepatocytes and
      renal tubules. In contrast to methylselenocysteine, selenite decreased
      intracellular ATP content, glutathione reduced/glutathione oxidized (GSH/GSSG)
      ratio and pyruvate carboxylase, PEPCK and FBPase activities, while
      methylselenocysteine diminished PEPCK activity due to elevation of intracellular
      2-oxoglutarate and GSSG, inhibitors of this enzyme. Experiments in vivo indicate
      that in 3 of 9 alloxan-diabetic rabbits treated for 14 days with
      methylselenocysteine (0.182mg/kg body weight) blood glucose level was normalized,
      whereas in all diabetic rabbits plasma creatinine and urea levels decreased from
      2.52+/-0.18 and 87.4+/-9.7 down to 1.63+/-0.11 and 39.0+/-2.8, respectively. In
      view of these data selenium supplementation might be beneficial for protection
      against diabetes-induced nephrotoxicity despite selenium accumulation in kidneys
      and liver.

PMID- 17222911
TI  - Preparation, structures and electrochemical property of phosphine substituted
      diiron azadithiolates relevant to the active site of Fe-only hydrogenases.
AB  - Mono- and di-phosphine diiron azadithiolate complexes [{(mu-SCH(2))(2)N(4
      NO(2)C(6)H(4))}Fe(2)(CO)(5)(PMe(3))] (2), [{(mu-SCH(2))(2)N(4
      NO(2)C(6)H(4))}{Fe(CO)(2)L}(2)] (3, L=PMe(3); 4, PMe(2)Ph) and the mu-hydride
      diiron complex [3(FeHFe)](+)[PF(6)](-) were prepared as biomimetic models of the
      active site of Fe-only hydrogenases. The complexes 2-4 and [3(FeHFe)](+)[PF(6)](
      ) were characterized by IR, (31)P, (1)H and (13)C NMR spectra and their molecular
      structures were determined by single crystal X-ray analyses. The PMe(3) ligand in
      complex 2 lies on the basal position. The PMe(3)-disubstituted complex 3 exists
      as two configuration isomers, transoid basal/basal and apical/basal, in the
      crystalline state, while two PMe(2)Ph ligands of 4 are in an apical/basal
      orientation. The variable temperature (31)P NMR spectra of 2 and 3 were made to
      have an insight into the existence of the possible conformation isomers of 2 and
      3 in solution. The [3(FeHFe)](+) cation possesses the sole transoid ba/ba
      geometry as other reported mu-hydride diiron analogues. The electrocatalytic
      property of {(mu-SCH(2))(2)NC(6)H(5)}[Fe(CO)(2)PMe(3)](2) (5) was studied for
      proton reduction in the presence of HOAc.

PMID- 17222912
TI  - Epidemiology of influenza in Hanoi, Vietnam, from 2001 to 2003.
AB  - OBJECTIVE: The aim of this study was to clarify the epidemiology of laboratory
      confirmed influenza in Hanoi, Vietnam. METHODS: Influenza was detected by virus
      isolation from nasopharyngeal swabs of influenza-like-illness (ILI) patients who
      reported to outpatient clinics in Hanoi, Vietnam between 2001 and 2003, before
      the start of avian influenza A/H5N1 outbreaks. Influenza isolates were
      characterized by hemagglutinin inhibition test. RESULTS: A total of 4708
      nasopharyngeal swabs were collected from patients with ILI. Influenza was
      positive in 119 (2.5%) samples by virus isolation. Influenza circulated
      throughout the year, with possible two peaks in summer and winter. Influenza B
      viruses and A/H3N2 predominated in 2001 and 2002, respectively, and mixed
      circulation of A/H1N1, A/H3N2 and B were observed in 2003. The seasonality of
      influenza roughly matched with clinical case reports in the North Region by
      National Communicable Disease Surveillance in Vietnam. CONCLUSIONS: The findings
      of year-round and biannual peak circulation of influenza in a subtropical area
      were in accordance with the results of previous studies in tropical and
      subtropical regions. Our observations indicated that establishment of laboratory
      based surveillance in tropical and sub-tropical countries is important for taking
      actions for pandemic strategies, and links to the WHO global influenza network.

PMID- 17222914
TI  - Molecular targets in cerebral ischemia for developing novel therapeutics.
AB  - Cerebral ischemia (stroke) triggers a complex series of biochemical and molecular
      mechanisms that impairs the neurologic functions through breakdown of cellular
      integrity mediated by excitotoxic glutamatergic signalling, ionic imbalance, free
      radical reactions, etc. These intricate processes lead to activation of
      signalling mechanisms involving calcium/calmodulin-dependent kinases (CaMKs) and
      mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated
      kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). The distribution of these
      transducers bring them in contact with appropriate molecular targets leading to
      altered gene expression, e.g. ERK and JNK mediated early gene induction,
      responsible for activation of cell survival/damaging mechanisms. Moreover,
      inflammatory reactions initiated at the neurovascular interface and alterations
      in the dynamic communication between the endothelial cells, astrocytes and
      neurons are thought to substantially contribute to the pathogenesis of the
      disease. The damaging mechanisms may proceed through rapid nonspecific cell lysis
      (necrosis) or by active form of cell demise (apoptosis or necroptosis), depending
      upon the severity and duration of the ischemic insult. A systematic understanding
      of these molecular mechanisms with prospect of modulating the chain of events
      leading to cellular survival/damage may help to generate the potential strategies
      for neuroprotection. This review briefly covers the current status on the
      molecular mechanisms of stroke pathophysiology with an endeavour to identify
      potential molecular targets such as targeting postsynaptic density-95 (PSD-95)/N
      methyl-d-aspartate (NMDA) receptor interaction, certain key proteins involved in
      oxidative stress, CaMKs and MAPKs (ERK, p38 and JNK) signalling, inflammation
      (cytokines, adhesion molecules, etc.) and cell death pathways (caspases, Bcl-2
      family proteins, poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis-inducing
      factor (AIF), inhibitors of apoptosis proteins (IAPs), heat shock protein 70
      (HSP70), receptor interacting protein (RIP), etc., besides targeting directly the
      genes itself. However, selecting promising targets from various signalling
      cascades, for drug discovery and development is very challenging, nevertheless
      such novel approaches may lead to the emergence of new avenues for therapeutic
      intervention in cerebral ischemia.

PMID- 17222913
TI  - The pharmacology of nitroxyl (HNO) and its therapeutic potential: not just the
      Janus face of NO.
AB  - Nitroxyl (HNO), the 1-electron reduced and protonated congener of nitric oxide
      (NO), has received recent attention as a potential pharmacological agent for the
      treatment of heart failure and as a preconditioning agent for the mitigation of
      ischemia-reperfusion injury. Interest in the pharmacology and biology of HNO has
      prompted examination, or in some instances reexamination, of many of its chemical
      properties. Such studies have provided insight into the chemical basis for the
      biological effects of HNO, although the biochemical mechanisms for many of these
      effects remain to be established. In this review, a brief description of the
      biologically relevant chemistry of HNO is given, followed by a more detailed
      discussion of the pharmacology and potential toxicology of HNO.

PMID- 17222916
TI  - Inflammatory processes in Alzheimer's disease.
AB  - Generation and deposition of amyloid beta peptides and neurofibrillary tangle
      formation are key mechanisms involved in AD pathogenesis. Recent evidence
      suggests that inflammatory mechanisms represent a third component which, once
      initiated by degeneration, may significantly contribute to disease progression
      and chronicity. Various neuroinflammatory mediators including complement
      activators and inhibitors, chemokines, cytokines, radical oxygen species and
      inflammatory enzymes are generated and released by microglia, astrocytes and
      neurons. Degeneration of aminergic brain stem nuclei such as the locus ceruleus
      and the nucleus baslis of Meynert may facilitate the occurrence of inflammation
      in their respective projection areas given the antiinflammatory and
      neuroprotective action of their key products norepinephrine and acetylcholine.
      While inflammation has been thought to arise secondary to degeneration, recent
      experiments demonstrated that inflammatory mediators may stimulate APP processing
      by upregulation of beta secretase 1 and therefore are able to establish a vicious
      cycle. Despite the fact that some aspects of inflammation may even exert
      protective effects to bystander neurons, antiinflammatory treatment strategies
      should therefore be considered. Non-steroidal antiinflammatory drugs have been
      shown to reduce the risk and delay the onset to develop AD. However, the precise
      molecular mechanism underlying this effect is still being debated. Several
      mechanisms including inhibition of cyclooxygenase 2, gamma secretase or
      activation of the peroxisome proliferator activated receptor gamma may alone or,
      more likely, in concert account for the epidemiologically observed protection.

PMID- 17222917
TI  - 'First, do no harm' with complementary and alternative medicine.

PMID- 17222915
TI  - Mood-worsening with high-pollen-counts and seasonality: a preliminary report.
AB  - BACKGROUND: Because aeroallergens produce inflammation in the respiratory
      airways, and inflammation triggers depression in vulnerable individuals, we
      hypothesized that mood sensitivity to pollen, the most seasonal aeroallergen,
      will be associated with a greater seasonality of mood. Since pollen is absent
      during winter, we specifically predicted that mood sensitivity to tree pollen
      will predict non-winter SAD but not winter SAD. METHODS: A convenience sample of
      African and African American college students who lived in the Washington DC
      metropolitan area for at least the past 3 years completed the Seasonal Pattern
      Assessment Questionnaire (SPAQ), from which the Global Seasonality Score (GSS)
      was calculated, a diagnosis of cumulative SAD (syndromal or subsyndromal SAD) was
      derived, a seasonal pattern (winter vs non-winter) identified, and self-reported
      mood changes during high pollen counts obtained. A Mann-Whitney test was used to
      compare GSS between participants with vs without mood worsening during high
      pollen counts. The capability of mood worsening with high pollen counts, gender,
      ethnicity, and age to predict non-winter SAD was analyzed with logistic
      regressions. RESULTS: GSS was greater (z=5.232, p<0.001) in those who reported
      mood worsening with high pollen counts. Mood sensitivity to pollen predicted non
      winter SAD (p=0.017), but not winter SAD. LIMITATIONS: The SPAQ is not a
      definitive tool to assess seasonality, and self-reported mood worsening with high
      pollen counts relies on recollection. No direct measures of depression scores or
      pollen counts were collected. The non-winter SAD concept has not been previously
      established. CONCLUSIONS: Our study, which should be considered preliminary in
      light of its limitations, suggests that self-reported mood-worsening with high
      pollen count is associated with a greater seasonality of mood, and predicts SAD
      of non-winter type.

PMID- 17222918
TI  - Development and application of a novel multiplex polymerase chain reaction for
      semi-quantitation of human Cytomegalovirus in clinical specimens.
AB  - Human Cytomegalovirus (HCMV) is an important cause of morbidity and occasional
      mortality in immunocompromised patients. The aims of the study were to develop
      and apply a multiplex PCR for semi-quantitation of HCMV in clinical specimens,
      compare its efficiency with pp65 antigenemia assay and real-time PCR. A multiplex
      PCR combining the primers targeting three regions of the HCMV genome, viz. the
      morphological transforming region II (mtr II), UL-83 and glycoprotein O (gO)
      genes for the detection of the genome of HCMV was standardized with HCMV AD169
      strain. This was evaluated against pp65 antigenemia assay by applying it on 70
      peripheral blood specimens obtained from 70 post-renal transplant recipients. The
      multiplex PCR and a real-time PCR were prospectively applied to 31 clinical
      specimens from 29 immunocompromised patients. The multiplex PCR was specific for
      HCMV. The level of antigenemia and the copy number of the viral DNA as estimated
      by real-time PCR in the samples positive for all the three targets was
      significantly higher than in those that were positive for only one or two of the
      targets. The multiplex PCR provides a simple and effective means of quantifying
      HCMV in clinical specimens with efficiency equivalent to the pp65 antigenemia
      assay and real-time PCR.

PMID- 17222919
TI  - The effects of a high-fat, high-fructose, and combination diet on learning,
      weight, and glucose regulation in C57BL/6 mice.
AB  - The objective of the study was to determine the effects of a high-fructose diet,
      a high-fat diet and a combination high-fructose/high-fat diet on weight gain,
      blood glucose regulation, and cognitive function in C57BL/6 mice. Thirty-eight
      male mice aged 7 weeks were placed on one of four different diets for 3 months:
      standard chow and water (n=8), standard diet and access to a fructose solution as
      the only intake of water (n=8), high-fat diet and water (n=11), and high-fat diet
      and fructose solution (n=11). Weights were measured 10 times over a 3-month
      period. Blood glucose regulation was measured using a glucose tolerance test.
      Cognitive testing consisted of learning an operant bar-pressing task and was
      performed in the absence of fructose intake. At the end of the experiment, the
      density of the fructose-specific glucose transporter GLUT5 was measured in the
      hippocampus, frontal cortex, sensori-motor cortex and cerebellum. The high-fat
      and the combined high-fat/high-fructose groups gained significantly more weight
      than the control group. The high-fat group and combined group had significantly
      higher levels of blood glucose than the control group. The high-fructose group
      learned the operant task faster than the control group, but the high-fat/high
      fructose group was not different from control indicating that the facilitative
      effect of prior fructose intake was abolished when a high-fat diet was added.
      Addition of fructose to the diet did not result in an increase of brain GLUT5
      density suggesting that the learning improvement were not dependent on plastic
      upregulation of GLUT5 fructose transporter. The results show that, contrary to
      high-fat diets, access to fructose in mice did not lead to increased weight and
      impaired glucose tolerance. The present experiment confirm the deleterious impact
      of high-fat diets on glucose regulation and weight but suggest that high-fructose
      diets, contrary to what has been observed in hamsters, do not have the same
      effect.

PMID- 17222920
TI  - Inferior olivary inactivation abolishes conditioned eyeblinks: extinction or
      cerebellar malfunction?
AB  - The inferior olive (IO) is a required component of neural circuits controlling
      the classical conditioning of eyeblink responses. Previous reports indicated that
      lesioning or inactivating the IO abolishes conditioned eyeblinks (CRs), but there
      was disagreement regarding the timing of the CR performance deficit. As a result,
      it was not clear whether IO inactivation produces unlearning of CRs or a non
      specific dysfunction of cerebellar circuits. Since most of these studies used
      methods that could block unrelated axons passing through the IO region,
      additional experiments are required to further elucidate IO function, using
      inactivating agents that act selectively on cell bodies. In the present study,
      the IO was inactivated using the glutamate receptor antagonist DGG and the GABA-A
      receptor agonist muscimol in rabbits performing well-learned CRs. Effects of
      inactivating the IO on CR expression and on neuronal activity in the anterior
      cerebellar interposed nucleus (IN) were examined. We found that either blocking
      excitatory glutamate inputs or activating inhibitory GABA inputs to the IO
      abolished CRs. This effect occurred with variable delay following drug
      injections. Additional experiments, in which post-injection testing was delayed
      to allow for drug diffusion, revealed invariably immediate suppression of CRs.
      This demonstrated that suppressing IO activity using DGG or muscimol does not
      induce unlearning of CRs. Single-unit recording during DGG injections revealed
      that CR suppression was paralleled by a dramatic suppression of IN neuronal
      activity. We concluded that inactivating the rostral parts of the IO complex
      abolishes CRs by producing a tonic malfunction of cerebellar eyeblink
      conditioning circuits.

PMID- 17222921
TI  - Gene expression profiles revealing the mechanisms of anti-androgen- and estrogen
      induced feminization in fish.
AB  - Environmental anti-androgens are increasingly being recognized as potential
      contributing factors in the chemically induced feminization of wild fish because,
      by blocking androgen action, they can produce phenotypic effects similar to
      environmental estrogens. The molecular mechanisms by which anti-androgens and
      estrogens exert feminizing effects, however, have not been systematically
      compared. Using a targeted approach, we profiled the expression responses of a
      suite of 22 genes involved in reproduction, growth and development (processes
      controlled by androgens and estrogens) in the liver and gonad in adult male and
      female fathead minnow (Pimephales promelas) exposed to the model anti-androgen
      flutamide and the model synthetic estrogen 17alpha-ethinylestradiol (EE(2)). Both
      flutamide (320 microg/L) and EE(2) (10ng/L) produced phenotypic effects
      indicative of feminization (induction of plasma vitellogenin, reduced
      gonadosomatic index, and reduced secondary sex characters), although for the
      chosen test concentrations EE(2) was the more potent. For the genes studied,
      flutamide and EE(2) produced distinct expression profiles, suggesting that they
      largely operate via distinct molecular mechanisms. As examples, in liver EE(2)
      (but not flutamide) exposure up-regulated estrogen receptor (ER) alpha mRNA,
      whereas flutamide exposure increased ERbeta and ERgamma mRNAs in males and
      resulted in decreased androgen receptor (AR) mRNA in females. In the testis,
      flutamide up-regulated genes coding for enzymes involved in androgen biosynthesis
      (cytochrome P450 17 [CYP17] and 11beta-hydroxysteroid dehydrogenase [11beta-HSD])
      implying an inhibitory action on androgen negative feedback pathways. EE(2), in
      contrast, inhibited the expression of enzymes involved in androgen biosynthesis
      (CYP17, 11beta-HSD and 17beta-hydroxysteroid dehydrogenase [17beta-HSD]). There
      were also some commonalities in the molecular mechanisms of flutamide and EE(2)
      action, including the down-regulation of gonadal sex steroid receptor expression
      (gonadal AR and ovarian ERalpha), increased expression of genes coding for
      estrogen-producing enzymes (cytochrome P450 19A and B [CYP19A and CYP19B]),
      decreased expression of genes involved in testis differentiation (anti-Mullerian
      hormone [AMH] and doublesex and mab-3 related transcription factor 1 [DMRT1]),
      and decreased expression of hepatic genes which mediate wider physiological
      processes such as somatic growth (growth hormone [GH], GH receptor [GHR], insulin
      like growth factor-I [IGF-I], IGF-I receptor [IGF-IR], thyroid hormone receptor
      alpha [TRalpha] and beta [TRbeta]).

PMID- 17222922
TI  - Overexpression, purification and characterization of a hexahistidine-tagged
      recombinant extended nucleotide-binding domain 1 (NBD1) of the Cryptosporidium
      parvum CpABC3 for rational drug design.
AB  - Its natural resistance to antiprotozoal chemotherapy characterizes the intestinal
      protozoan parasite Cryptosporidium parvum and the P-glycoprotein-related
      multidrug resistance proteins such as CpABC3 could be involved. In order to
      design and study specific inhibitors of the CpABC3 nucleotide-binding domain, a
      hexahistidine-tagged recombinant protein encompassing the N-terminal cytosolic
      NBD1 domain was overexpressed in E. coli and purified. The 45 kDa H6-NBD1
      displayed intrinsic fluorescent properties consistent with the presence of two
      Trp residues in a hydrophobic environment. The binding of ATP and the fluorescent
      analogue TNP-ATP produced a dose-dependent quenching as well as progesterone and
      the flavone quercetin. The extrinsic fluorescence of TNP-ATP was enhanced upon
      binding to H6-NBD1, which was only partially displaced by the natural substrate
      ATP. The recombinant protein hydrolyzed ATP (K(m)=145.4+/-18.2 microM), but ADP
      (K(m)=4.3+/-0.6mM) and AMP (K(m)=5.4+/-1.5 microM) were also substrates. TNP-ATP
      is a competitive inhibitor of the catalytic activity (K(i)=36.6+/-4.5 microM),
      but quercetin and progesterone were not inhibitors, evidencing different binding
      sites. The recombinant C. parvum H6-NBD1 should be a valuable tool for rational
      drug design and will allow the discrimination between specific inhibitors of the
      catalytic site and molecules binding to other sites.

PMID- 17222923
TI  - The apicomplexan parasite Toxoplasma gondii generates pyridoxal phosphate de
      novo.

PMID- 17222924
TI  - Vasodilator effects of peptides derived from egg white proteins.
AB  - The aim of this work was to investigate the effect of several peptides,
      identified before and after simulated gastrointestinal digestion of an egg white
      hydrolysate, on the vascular function, in rat aorta. The sequences IVF, RADHPFL
      and YAEERYPIL (0.1 mM) induced vasodilatation in intact aortic rings, with the
      maximum percentage of dilation corresponding to RADHPFL (40.5+/-7.0%). Two of the
      end products of the gastrointestinal digestion, RADHP and YPI, also showed
      vasodilator activity with degrees of relaxation higher than 50%. However, all
      these peptides failed to induce relaxation in endothelium-denuded aortic rings.
      The relaxation induced by RADHP was concentration-dependent and it was partially
      blocked by the nitric oxide synthase inhibitor L-NAME (100 microM) and by the
      B(1) bradykinin receptor antagonist Des-HOE 140 (30 nM), thus showing that it was
      mediated by NO production through the activation of B(1) bradykinin receptors.
      These findings suggest that these peptides could reduce the vascular resistance
      and could be used as functional food ingredients in the prevention and treatment
      of hypertension.

PMID- 17222925
TI  - Relationship of thyroid stimulating hormone with coronary atherosclerosis in
      angina patients.
AB  - BACKGROUND: In the previous recent reports, subclinical hypothyroidism is an
      independent risk factor for acute myocardial infarction in elderly women. It was
      not established whether a normal range of thyroid stimulating hormone (TSH)
      influences the presence of coronary atherosclerosis. We postulated that the level
      of TSH is risk factor of coronary atherosclerosis in angina patients who have
      normal thyroid function. METHODS: We studied 344 angina patients (62.5+/-9.72
      years, male 50%) who underwent elective coronary angiography. TSH, free
      thyroxine, serum lipid levels and high-sensitivity C-reactive protein levels were
      measured and compared to the severity of coronary artery disease. RESULTS: In
      patients with high level of TSH (> or =2.1 microIU/mL), age (p=0.016), the levels
      of serum creatinine (p=0.004) and Gensini's score (p=0.016) were significantly
      higher than those in patients with low TSH levels. The incidence of multi-vessel
      disease was higher in patients with high TSH level (p=0.026). TSH level showed a
      significant correlation with age (r=0.109, p=0.044) and Gensini's score (r=0.117,
      p=0.045). The multivariate analysis revealed that age (OR 2.39, p=0.001),
      diabetes (OR 3.74, p=0.001), creatinine (OR 2.06, p=0.008), and smoking (OR 1.85,
      p=0.045) were independent predictors for significant coronary artery disease, but
      TSH level did not predict coronary artery stenosis. CONCLUSIONS: Although the
      high level of serum TSH is associated with multi-vessel disease, it was not the
      determinant of coronary artery disease in patients with normal range of thyroid
      function.

PMID- 17222926
TI  - Ximelagatran/melagatran against conventional anticoagulation: a meta-analysis
      based on 22,639 patients.
AB  - BACKGROUND: The oral direct thrombin inhibitor ximelagatran, and its active form,
      melagatran, have been tested in various clinical conditions as a promising
      alternative to conventional anticoagulant therapy (CAT), despite some concerns
      over potentially serious liver injury. OBJECTIVES: To assess its risk/benefit
      profile, a systematic review and meta-analysis of all randomised controlled
      trials (RCTs) comparing xi-/melagatran to CAT was performed. METHODS: Leading
      medical databases were searched. The rates of major adverse events (MAE: all
      cause death, nonfatal myocardial infarction, nonfatal thromboembolic stroke,
      nonfatal pulmonary embolism), major bleeds (MB), and hepatotoxicity were
      compared. Out of 140 potentially relevant citations, 13 RCTs enrolling 22,639
      patients were included. Indications for treatment were: 1) perioperative
      prophylaxis of deep vein thrombosis (DVT); 2) management of DVT; and 3) stroke
      prevention in atrial fibrillation. RESULTS: Overall, the risk of MAE (OR 0.98
      [0.83-1.17]) and MB (OR 1.01 [0.69-1.47]) did not differ significantly between xi
      /melagatran and CAT. There was a clear trend towards an increased risk of
      hepatotoxicity (OR 1.74 [0.50-6.01]), with an incidence of 5.8% with xi
      /melagatran versus 2.3% with CAT (p<0.001); more specifically, the rate of
      hepatotoxicity was markedly augmented in the management of DVT (OR 5.16 [3.38
      7.89]), for treatment durations > or = 3 months (OR 6.73 [5.01-9.05]), and in the
      prevention of atrial fibrillation-related stroke (OR 8.31 [5.65-12.23]). Two
      fatal cases of liver injury occurred with xi-/melagatran. CONCLUSIONS: Although
      comparable to CAT in terms of MAE and MB, xi-/melagatran carries a prohibitive
      risk of hepatotoxicity that cannot be ignored. Newer long-term alternatives are
      urgently needed.

PMID- 17222927
TI  - Prognostic impact of peakVO2-changes in stable CHF on chronic beta-blocker
      treatment.
AB  - BACKGROUND: Peak oxygen uptake (pVO2) is used for risk stratification in chronic
      heart failure (CHF), but little is known about the prognostic impact of pVO2
      changes in patients on chronic beta-blocker (BBL) therapy. We therefore
      prospectively evaluated individual pVO2-changes at a 6-month interval in patients
      all receiving BBL. METHODS: 194 patients with stable CHF on stable medication
      were included (V1) and underwent clinical evaluation and exercise testing.
      Testing was repeated (V2) at 5.7+/-1.5 months after V1 and patients were followed
      >12 months after V2. Death or hospitalisation due to cardiac reasons was the
      predefined EP (EPP, end-point positive; n=62; EPN, end-point negative; n=113).
      RESULTS: Initial characteristics did not differ between EPP and EPN. Multivariate
      cox regression analysis revealed that change of pVO2 (EPP: -0.6+/-2.6 ml/kg min;
      EPN: +2.5+/-3.3 ml/kg min; p<0.001) was independent to pVO2, LVEF, NTproBNP and
      NYHA at V2 for prediction of the combined end-point during follow-up. An increase
      of pVO2 by 10% was identified as an adequate cut-off value for risk
      stratification and ROC-analysis showed the significant incremental prognostic
      value of the determination of pVO2 changes in combination with pVO2. CONCLUSIONS:
      Serial measurements of pVO2 yield additional information for risk stratification
      in clinically homogenous CHF patients receiving BBL. This is the first study
      demonstrating this fact within a narrow predefined interval with all patients on
      BBL.

PMID- 17222928
TI  - Free-floating ball thrombus in the left ventricle with dilated cardiomyopathy.

PMID- 17222929
TI  - Spatial analysis of bovine spongiform encephalopathy in Galicia, Spain (2000
      2005).
AB  - In Spain, the first bovine spongiform encephalopathy (BSE) case was detected in
      2000 in a cow born in the Galicia region (Northwestern Spain). From then and
      until October 2005, 590 cases were detected, 223 of them in Galicia. In 1994,
      meat and bone meal (MBM) was banned on ruminant feed and, in 1996, an EU decision
      mandating an overall change in MBM processing was implemented. This decision was
      gradually applied in the territory and not enforced before July 1998. The
      objective of this study was to explore clustering of BSE cases and estimate the
      standard incidence ratio (SIR) of BSE in Galicia. Our study was based on the BSE
      cases detected during the surveillance period 2000-2005 in the Galicia region.
      These cases were divided, based on birth date, into two periods: animals born
      from 1994 to July 1998, and those born after July 1998. We tested the role of
      cross-contamination on the geographical SIR distribution for both periods.
      Hierarchical Bayesian models were used to model the overdispersion and lack of
      independence of the SIR estimates. The geographical distribution of the standard
      incidence ratio of BSE between both periods was different. In the second period,
      the SIR was reduced in some areas. The reduction in these areas could be
      attributable to the changes in the processing of MBM. We did not find any
      statistical link between the poultry population and the standard incidence ratio,
      but pig population had a positive effect.

PMID- 17222930
TI  - Explaining China's regional health expenditures using LM-type unit root tests.
AB  - This paper investigates the relationship between health care expenditure, income,
      and other factors that are not related to income for China with pooled cross
      section and time series data. To study the stationarity property of these
      variables, we use panel Lagrange Multiplier (LM) unit root tests that allow for
      structural changes. To perform the LM unit root tests, we employ finite-sample
      critical values derived through the bootstrap method, instead of relying on the
      critical values from the asymptotic normal distribution. An important finding
      based on the estimated panel cointegrated regressions is that the government
      budget deficits have a significant long-run impact on China's health care
      expenditure. This provides supportive evidence on the differences between rich
      and poor areas in China's health care financing policy, and the substantial
      disparities in health service coverage in China.

PMID- 17222931
TI  - Intensity-modulated radiation therapy for prostate cancer: late morbidity and
      results on biochemical control.
AB  - PURPOSE: To report on late morbidity and biochemical relapse-free survival (bRFS)
      after intensity-modulated radiation therapy (IMRT) for prostate cancer. METHODS:
      Between 1998 and 2005 133 patients were treated with IMRT for T(1-4) N0 M0
      prostate cancer. The median follow-up time was 36 months. In a first cohort,
      patients received a median planning target volume (PTV) dose of 74 Gy with a hard
      constraint on maximum rectum dose of 72 Gy (74R72, n=51). Later, median PTV and
      maximum rectum dose were increased to 76 and 74 Gy, respectively (76R74; n=82).
      We defined low-risk (n=20), intermediate-risk (n=70) and high-risk (n=43) groups.
      Androgen deprivation was given to patients in the intermediate- and high-risk
      group. Late gastro-intestinal (GI) and genito-urinary (GU) morbidity and
      biochemical relapse, in accordance with the ASTRO consensus, were recorded.
      RESULTS: We observed grade 2 GI (17%) and GU (19%), grade 3 GI (1%) and GU (3%)
      late toxicities. Except for hematuria, the median duration of side-effects was 6
      months. Biochemical relapse-free survival (bRFS) at 3 and 5 years was 88% and
      83%, respectively, with a significantly better 3-year bRSF for the 76R74 than for
      the 74R72 group (p=0.01). Five-year bRFS for patients in the low-risk,
      intermediate-risk and high-risk group was 100%, 94% and 74%, respectively
      (p<0.01). CONCLUSION: IMRT for localized or locally advanced prostate cancer
      combines low morbidity with excellent biochemical control.

PMID- 17222932
TI  - The isolation of neural stem cells from the olfactory bulb of Parkinson's disease
      model.
AB  - Hyposmia is one of the characteristic symptoms of PD. We isolated the neurosphere
      forming cells (NSFCs) from the olfactory bulb (OB) after dopaminergic neuronal
      loss induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is a
      model of Parkinson's disease. We used BrdU to label dividing cells and isolated
      NSFCs from the OB of adult mice with or without MPTP to confirm the function of
      OB in PD models. Seven days after MPTP treatment, BrdU-positive cells were
      significantly increased in the OB, especially in the glomerular layer (GL) and
      the subependymal zone (SEZ). The number of neurospheres derived from the adult OB
      was not decreased in groups receiving MPTP, instead, it was significantly
      increased at 21 days post-injection and only returned to control levels 40 days
      after MPTP administration. We also evaluated the differentiation of NSFCs into
      neural subtypes and found that these NSFCs could be well infected with
      retrovirus. Adult neurogenesis may be enhanced as a repair system in the tyrosine
      hydroxylase (TH) positive cells of the OB after MPTP administration. The
      isolation of neural stem cells from the OB after MPTP administration has helped
      to establish the cellular basis of neurogenesis and supports a role for the
      transplant-mediated treatment of PD.

PMID- 17222933
TI  - Trehalose phosphorylase from Pleurotus ostreatus: characterization and
      stabilization by covalent modification, and application for the synthesis of
      alpha,alpha-trehalose.
AB  - Trehalose phosphorylase from the basidiomycete Pleurotus ostreatus (PoTPase) was
      isolated from fungal fruit bodies through approximately 500-fold purification
      with a yield of 44%. Combined analyses by SDS-PAGE and gelfiltration show that
      PoTPase is a functional monomer of approximately 55 kDa molecular mass. PoTPase
      catalyzes the phosphorolysis of alpha,alpha-trehalose, yielding alpha-d-glucose 1
      phosphate (alphaGlc 1-P) and alpha-d-glucose as the products. The optimum pH of
      PoTPase for alpha,alpha-trehalose phosphorolysis and synthesis is 6.8 and 6.2,
      respectively. Apparent substrate binding affinities (K(m)) were determined at pH
      6.8 and 30 degrees C: alpha,alpha-trehalose (79 mM); phosphate (3.5 mM); d
      glucose (40 mM); alphaGlc 1-P (4.1mM). A series of structural analogues of d
      glucose were tested as glucosyl acceptors for the enzymatic reaction with
      alphaGlc 1-P, and robust activity with d-mannose (3%), 2-deoxy d-glucose (8%), 2
      fluoro d-glucose (15%) and 2-keto-d-glucose (50%) was detected. Arsenate
      replaces, with 30% relative activity, phosphate in the conversion of alpha,alpha
      trehalose, and vanadate strongly inhibits the enzyme activity (K(i) approximately
      4 microM). PoTPase has a half-life (t(0.5)) of approximately 1 h at 30 degrees C
      in the absence of stabilizing compounds such as alpha,alpha-trehalose (300 mM;
      t(0.5)=11.5 h), glycerol (20%, w/v; t(0.5)=6.5h) or polyethylenglycol (PEG) 4000
      (26%, w/v; t(0.5)=70 h). Covalent modification of PoTPase with activated
      derivatives of PEG 5000 increases the stability by up to 600-fold. Sucrose was
      converted to alpha,alpha-trehalose in approximately 60% yield using a coupled
      enzyme system composed of sucrose phosphorylase from Leuconostoc mesenteroides,
      glucose isomerase from Streptomyces murinus and the appropriately stabilized
      PoTPase.

PMID- 17222934
TI  - Current status of technical protein refolding.
AB  - The expression of heterologous proteins in microbial hosts frequently leads to
      the formation of insoluble aggregates. To fully exploit the production capacity
      of the cells, efficient strategies for further processing have to be developed.
      While in lab scale matrix assisted refolding techniques, especially of histidine
      tagged proteins have become very popular, in production scale refolding by
      dilution is still predominant due to its simplicity. However scaling up dilution
      processes leads to large volumes and low protein concentration. This is a heavy
      burden both for liquid handling and for subsequent downstream processing steps.
      Process development aims to operate at uniform, reproducible conditions, to
      reduce costs to a minimum and to guarantee the required quality of the product.
      The general refolding kinetics, exploration of appropriate refolding conditions
      are reviewed. The major refolding operations such as dilution, matrix assisted
      refolding, pressure driven refolding or continuous refolding applications are
      discussed in view of industrial applicability.

PMID- 17222935
TI  - Control of 2-chlorophenol vapour emissions by a trickling biofilter.
AB  - This research work investigates the biodegradation of 2-chlorophenol vapours in a
      trickling biofilter packed with a ceramic material, and seeded with a pure strain
      of Pseudomonas pickettii. The process was tested at laboratory scale over 260
      days of operation under varying loading conditions. More than 98% degradation
      efficiencies were achieved for loading rates up to 82.5gm(-3)h(-1). Process
      analysis, performed using data on 2-chlorophenol concentration profiles along the
      biofilter bed, shows that best biofilter performance (i.e. maximum degradation
      capacity and efficiency) can be obtained for a narrow range of operating
      conditions, which can be ensured by proper sizing of biofilter diameter and
      height.

PMID- 17222936
TI  - Identification of neutralizing linear epitopes from the VP1 capsid protein of
      Enterovirus 71 using synthetic peptides.
AB  - Enterovirus 71 (EV71) is the main causative agent of Hand, foot and mouth disease
      (HFMD) and has been associated with severe neurological diseases resulting in
      high mortalities. Currently, there is no vaccine available and treatment is
      limited to palliative care. In this study, antisera were raised in mice against
      95 overlapping synthetic peptides spanning the VP1 capsid protein of EV71. Two
      peptides, SP55 and SP70, containing amino acid 163-177 and 208-222 of VP1,
      respectively, are capable of eliciting neutralizing antibodies against EV71 in
      the in vitro microneutralization assay. SP70 was identified to be particularly
      potent in eliciting a neutralizing antibody titer comparable to that obtained
      with a whole virion-immune serum. Immunization of mice with either SP55 or SP70
      triggered an EV71-specific IgG response as high as that obtained with the whole
      virion as immunogen. The IgG sub-typing revealed that the neutralizing antibodies
      elicited by both synthetic peptides are likely belonging to the IgG1 sub-type.
      Alignment with databases showed that the amino acid residues of SP70 are highly
      conserved amongst the VP1 sequences of EV71 strains from various sub-genogroups.
      Altogether, these data indicate that SP70 represents a promising candidate for an
      effective synthetic peptide-based vaccine against EV71.

PMID- 17222937
TI  - Expression of short hairpin RNAs against the coxsackievirus B3 exerts potential
      antiviral effects in Cos-7 cells and in mice.
AB  - Chemically synthesized small interfering RNA (siRNA) has been used as an anti
      coxsackievirus B3 (CVB3) agent. Herein, we investigated whether vector-derived
      short hairpin RNAs (shRNA) targeting CVB3 can exert antiviral activities, prior
      to their further application to viral vector system for efficient in vivo
      administration. Employing transient transfection assays to in vivo mouse models
      as well as to in vitro Cos-7 cell cultures, we directly demonstrated the
      potential antiviral activity of shRNAs following challenges with infectious CVB3.
      Of the six shRNAs that we designed, three prevented cell death from CVB3
      infection by suppressing viral replication and viral production in Cos-7 cells.
      These were shRNA 2, which targeted the capsid protein VP1, and shRNAs 4 and 5,
      which targeted two different regions of the RNA-dependent RNA polymerase 3D.
      Furthermore, shRNAs 2 and 5 also exerted strong antiviral effects in viral
      replication in vivo, accompanied by attenuated pancreatic tissue damage. Through
      this direct evaluation system we addressed the development and application of
      vector-derived shRNAs as an anti-CVB3 agent, revealing new target sequences.

PMID- 17222938
TI  - Genetic polymorphisms and treatment response in advanced non-small cell lung
      cancer.
AB  - BACKGROUND: Genetic polymorphisms involved in DNA repair and apoptosis are
      suspected to influence patient response to cancer treatment. To evaluate the
      effect of genetic variations on chemotherapy and/or radiotherapy, we genotyped
      four single nucleotide polymorphisms (SNPs) in ATM (A60G), ERCC1 (Asn118Asn),
      APE1 (Asn148Glu), and iASPP (A67T), and examined their associations with
      treatment response among patients with advanced non-small cell lung cancer
      (NSCLC). METHODS: Included in the study were 230 patients diagnosed with
      inoperable advanced NSCLC. Of these patients, 76 received platinum-based
      chemotherapy, 125 received chemotherapy plus radiation, and 29 received
      radiotherapy only. The SNPs were genotyped using the TaqMan methods. RESULTS:
      Among the patients who received chemotherapy only, ERCC1 (Asn118Asn) genotype was
      significantly associated with treatment response. Patients with either one or two
      T alleles (T/T+C/T) at Asn118Asn were more likely not to respond to platinum
      based chemotherapy compared to those without the T allele (OR=4.10, 95% CI: 1.31
      12.85). For patients who were treated with both chemotherapy and radiotherapy,
      treatment response seemed to differ substantially between patients with different
      genotypes of iASPP (A67T). Patients carrying an A allele (A/T+A/A) at A67T were
      more likely to respond to combined chemotherapy and radiotherapy compared to
      those not carrying the A allele (OR=0.25, 95% CI: 0.08-0.74). An association with
      treatment response was also suggested for the selected polymorphism in APE1, but
      no association was found for the ATM polymorphism. CONCLUSION: We found that SNPs
      in ERCC1 and iASPP were associated with response to chemotherapy or combined
      chemotherapy and radiotherapy in NSCLC patients. These findings support the
      notion that genetic variations related to DNA repair or apoptosis may affect the
      effect of chemotherapy or radiation on NSCLC.

PMID- 17222939
TI  - Implementing emergency research requiring exception from informed consent,
      community consultation, and public disclosure.
AB  - Conducting emergency research in the out-of-hospital and emergency department
      setting is a challenge because of the inability of patients to provide informed
      consent in many situations. Federal guidelines allowing research under an
      exception from informed consent for emergency research have been established (21
      CRF 50.24). Community consultation and public disclosure, 2 required components
      of obtaining this exception, are seen by many as a barrier to resuscitation
      research. This article will provide a brief overview of the history of the
      exception from informed consent for emergency research and summarize our methods
      recently used to successfully complete community consultation and public
      disclosure for a trial evaluating 2 devices used during cardiopulmonary
      resuscitation in a large metropolitan area.

PMID- 17222940
TI  - Ultrasonographic confirmation of intraosseous needle placement in an adult
      unembalmed cadaver model.
AB  - STUDY OBJECTIVE: Intraosseous access is widely used in pediatric and adult
      resuscitations when vascular access cannot be promptly established. Confirmation
      of intraosseous needle placement has traditionally relied on the ability to
      aspirate blood or marrow or infuse crystalloid easily. This study's aim is to
      determine the value of bedside ultrasonography as a means of confirming
      intraosseous needle placement by visualizing the flow of crystalloid within the
      intraosseous space. METHODS: A controlled trial was conducted in which
      intraosseous access was obtained in the bilateral distal tibia of 4 freshly
      frozen, unembalmed cadavers. In 8 legs, an intraosseous needle (15-gauge
      Jamshidi) was inserted 1 fingerbreadth superior to the medial malleolus and
      flushed with 10 mL of crystalloid. Measurements included whether crystalloid was
      observed to flow by gravity into the drip reservoir of the intravenous tubing and
      whether color flow was visualized within the intraosseous space of the tibia with
      a 5- to 10-MHz linear transducer in color power Doppler mode, positioned just
      cephalad to the intraosseous needle. Intraosseous needles were then intentionally
      placed into the subcutaneous space just posterior to the distal tibia, and these
      measurements were repeated. Two blinded observers reviewed ultrasonographic video
      recordings and rated the presence or absence of color flow within the
      intraosseous space. RESULTS: Intraosseous color flow on ultrasonography correctly
      identified all placements, but flow into the drip reservoir was incorrect for one
      of the intraosseous lines (P=1.0 versus ultrasonography) and 6 of the
      subcutaneous lines (P=0.31 versus ultrasonography). There was perfect
      interobserver agreement (kappa=1) during video review. CONCLUSION: In freshly
      frozen cadavers, ultrasonographic visualization of flow within the intraosseous
      space may be a reliable method of confirming intraosseous placement. The
      observation of flow into the drip reservoir appears to be an unreliable indicator
      of intraosseous placement in fresh frozen cadavers.

PMID- 17222941
TI  - Capnography for procedural sedation and analgesia in the emergency department.
AB  - Although it is standard of care for patient safety monitoring in anesthesia,
      capnography is not routinely used for emergency department procedural sedation
      and analgesia. We discuss the use of capnography as a diagnostic monitoring
      modality for procedural sedation and analgesia, focusing on the physiology and
      interpretation of the CO2 waveform and recognition of normal, abnormal, and drug
      induced ventilatory patterns.

PMID- 17222942
TI  - Vasodilatory effect of tuberoinfundibular peptide (TIP39): requirement of
      receptor desensitization and its beneficial effect in the post-ischemic heart.
AB  - Tuberoinfundibular peptide of 39 residues (TIP39) is a member of the parathyroid
      hormone (PTH) family and a highly specific ligand of the PTH-receptor type 2 (PTH
      2r). Recent studies have shown vasoactive properties of TIP39 in the kidney. This
      effect was stronger after desensitization of the parathyroid hormone-receptor
      type 1 (PTH-1r). The aims of our study were three-fold: (1) to investigate the
      influence of TIP39 on coronary resistance (CR), (2) to investigate a possible
      cross-talk between vascular PTH-receptors in the cardiovascular system, and (3)
      to investigate whether the endogenously released PTHrP during ischemia induces
      such a desensitizing effect. Experiments were performed on isolated rat hearts
      that were perfused with a constant pressure (Langendorff mode) and the coronary
      flow was determined. Under basal conditions, TIP39 showed no influences on CR.
      However, TIP39 reduced the CR by approximately 22% after pre-treatment of the
      hearts with a PTH-1r agonist. This TIP39 effect was abolished either by co
      administration of a PTH-2r antagonist or by inhibition of nitric oxide (NO)
      formation. In an ischemia-reperfusion model endogenously released PTHrP
      desensitized the PTH-1r and pre-ischemic addition of TIP39 reduced post-ischemic
      CR by about 28%. Again, this effect was completely abolished in the presence of
      the PTH-2r antagonist or the PTH-1r-antagonist or by inhibition of NO formation.
      However, no effect was observed when TIP39 was washed-out prior to ischemia or if
      the treatment with TIP39 was restricted to the reperfusion. Furthermore, a pre
      ischemic application of the NO-dependent vasorelaxant bradykinin provoked a
      similar effect on the post-ischemic CR than TIP39. In conclusion, a NO-dependent
      vasodilatory effect of TIP39 was demonstrated if the PTH-1r is desensitized by
      either exogenously applicated PTHrP peptides or endogenously released PTHrP.

PMID- 17222943
TI  - NPY Y1 receptor is not involved in the hemodynamic response to an acute cold
      pressor test in mice.
AB  - The vasoconstrictor neuropeptide Y (NPY) has been shown to down-regulate tyrosine
      hydroxylase expression in cultured adrenal chromaffin cells, which probably
      accounts for the higher plasma resting norepinephrine (NE) and epinephrine (E)
      concentrations observed in Y(1) knock-out mice (Y(1)-/-) than in wild-type mice
      (Y(1)+/+). The aim of this work was to study the hemodynamic response of Y(1)-/-
      mice to an acute stimulation of the sympathetic nervous system (cold pressor
      test, CPT). Plasma catecholamine concentrations were higher in Y(1)-/- mice than
      in wild-type animals at the end of the CPT. The CPT-induced increase in mean
      arterial blood pressure (MAP) and heart rate (HR) was similar in both genotypes.
      Independently of the genotype, females had significantly slower HR than males
      throughout the 15min duration of the CPT. There was no difference in the
      sensitivity of the baroreceptor reflex, as reflected by the change in HR divided
      by the concurrent change in MBP between Y(1)-/- and Y(1)+/+ mice. In conclusion,
      mice lacking the Y(1) receptor can maintain normal hemodynamic response to an
      acute activation of the sympathetic system, albeit at the expense of increased
      catecholamine discharge.

PMID- 17222944
TI  - Motilin activates neurons in the rat amygdala and increases gastric motility.
AB  - Motilin and motilin receptors have been found in most regions of the brain,
      including the amygdala, one of the most important parts of the limbic system. Our
      previous study found that administration of motilin in the hippocampus stimulates
      gastric motility. We now explore the effect of motilin in the amygdala on gastric
      motility. In conscious rats, gastric motility was recorded after microinjection
      of motilin, motilin receptor antagonist (GM-109) or a mixture of the two into the
      basomedial amygdala nucleus (BMA). In anesthetized rats the changes of
      spontaneous discharges of gastric distention sensitive neurons (GDSN) in the BMA
      were recorded after intracerebroventricular (i.c.v.) microinjection of motilin or
      GM-109. In conscious rats the amplitude of gastric contractions increased dose
      dependently after microinjection of motilin in the BMA, and decreased after
      microinjection of GM-109. The excitatory or inhibitory effects induced by motilin
      or GM-109 alone, were weakened by microinjection of a mixture solution of both.
      The spontaneous discharge frequency of gastric distention excitatory neuron
      (GDEN) was mainly inhibited by i.c.v. microinjection of motilin but excited by GM
      109. In contrast, the spontaneous discharge frequency of gastric distention
      inhibitory neuron (GDIN) was mainly excited by motilin, but inhibited by GM-109.
      Our findings suggest that motilin may regulate gastric motility by modulating
      neural pathways in the BMA.

PMID- 17222945
TI  - NPY regulates human endocardial endothelial cell function.
AB  - Growing evidence suggests that endocardial endothelial cells (EECs) may play an
      important role in the regulation of cardiac function by releasing several
      cardioactive factors such as endothelin-1 (ET-1), Angiotensin II (Ang II) and
      nitric oxide (NO). In our laboratory, we demonstrated that similar to ET-1, EECs
      do possess different types of NPY receptors, specifically Y(1) and Y(2)
      receptors. Furthermore, activation of these receptors was found to increase the
      steady-state level of intracellular free Ca(2+) in EECs and the frequency of
      beating of cardiomyocytes. In addition, NPY was also found to be present in EECs,
      and an increase of steady-state intracellular free Ca(2+) induced the release of
      this peptide from these cells. Thus, similar to ET-1, NPY seems to be released
      from EECs and this peptide seems to regulate excitation-secretion of these cells
      as well as excitation-contraction coupling of ventricular cardiomyocytes.

PMID- 17222947
TI  - Multiple roles for poly(ADP-ribose)polymerase-1 in neurological disease.
AB  - Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear protein activated by DNA
      damage. PARP-1 activation is associated in DNA repair, cell death and
      inflammation. Since oxidative stress induced robust DNA damage and wide spread
      inflammatory responses are common pathologies of various CNS diseases, the
      interest toward PARP-1 as a therapeutic target has peaked. This review introduces
      mechanism of PARP-1 activation, the role of PARP-1 in cell physiology and
      pathology, and discusses the potential of PARP-1 inhibition as a therapy in acute
      and chronic CNS diseases.

PMID- 17222946
TI  - Low abundance of NPY in the hypothalamus can produce hyperphagia and obesity.
AB  - States of increased metabolic demand are associated with up-regulation of NPY and
      hyperphagia. However, we present some instances of hyperphagia in which NPY is
      not up-regulated. Ablation or functional disruption of specific sites in the
      hypothalamus, such as the ventromedial or paraventricular nuclei, or transection
      of inputs to the hypothalamus from the hindbrain results in hyperphagia and
      excess body weight gain. However, NPY expression and concentration in these
      experimental models is either decreased or unchanged. While there is no up
      regulation of NPY in these models, there is increased sensitivity to the
      orexigenic effects of NPY. This enhanced responsiveness to NPY may more than
      compensate for the reduced levels of NPY and result in hyperphagia and excess
      body weight gain. The hyper-responsiveness may be due either to an increase in
      NPY receptors or to other changes in target cells and response pathways that may
      result from the treatments used in these models.

PMID- 17222948
TI  - Modulation of synaptic plasticity and Tau phosphorylation by wild-type and mutant
      presenilin1.
AB  - The function of presenilin1 (PS1) in intra-membrane proteolysis is undisputed, as
      is its role in neurodegeneration in FAD, in contrast to its exact function in
      normal conditions. In this study, we analyzed synaptic plasticity and its
      underlying mechanisms biochemically in brain of mice with a neuron-specific
      deficiency in PS1 (PS1(n-/-)) and compared them to mice that expressed human
      mutant PS1[A246E] or wild-type PS1. PS1(n-/-) mice displayed a subtle impairment
      in Schaffer collateral hippocampal long-term potentiation (LTP) as opposed to
      normal LTP in wild-type PS1 mice, and a facilitated LTP in mutant PS1[A246E]
      mice. This finding correlated with, respectively, increased and reduced NMDA
      receptor responses in PS1[A246E] mice and PS1(n-/-) mice in hippocampal slices.
      Postsynaptically, levels of NR1/NR2B NMDA-receptor subunits and activated alpha
      CaMKII were reduced in PS1(n-/-) mice, while increased in PS1[A246E] mice. In
      addition, PS1(n-/-) mice, displayed reduced paired pulse facilitation, increased
      synaptic fatigue and lower number of total and docked synaptic vesicles, implying
      a presynaptic function for wild-type presenilin1, unaffected by the mutation in
      PS1[A246E] mice. In contrast to the deficiency in PS1, mutant PS1 activated GSK
      3beta by decreasing phosphorylation on Ser-9, which correlated with increased
      phosphorylation of protein tau at Ser-396-Ser-404 (PHF1/AD2 epitope). The
      synaptic functions of PS1, exerted on presynaptic vesicles and on postsynaptic
      NMDA-receptor activity, were concluded to be independent of alterations in GSK
      3beta activity and phosphorylation of protein tau.

PMID- 17222949
TI  - Presenilins regulate the cellular level of the tumor suppressor PTEN.
AB  - Alzheimer's Disease (AD) is characterized by amyloid plaques consisting of beta
      amyloid (Abeta) peptides and neurofibrillary tangles consisting of
      hyperphosphorylated tau protein. Abeta is proteolytically derived from its
      precursor protein through cleavages by beta-secretase and gamma-secretase complex
      comprising presenilins (PS, PS1/PS2), nicastrin, APH-1 and PEN-2. PS1 is also
      known to activate the PI3K/Akt cell survival pathway in a gamma-secretase
      independent manner. The tumor suppressor PTEN, which antagonizes the PI3K/Akt
      pathway, has increasingly been recognized to play a key role in neural functions
      and its level found reduced in AD brains. Here, we demonstrate that the protein
      level of PTEN is dramatically reduced in cultured cells and embryonic tissues
      deficient in PS, and in the cortical neurons of PS1/PS2 conditional double
      knockout mice. Restoration of PS in PS-deficient cells reverses the reduction of
      PTEN. Regulation of PTEN by PS is independent of the PS/gamma-secretase activity
      since impaired gamma-secretase by the gamma-secretase inhibitor treatment or due
      to nicastrin deficiency has little effect on the protein level of PTEN. Our data
      suggest an important role for PS in signaling pathways involving PI3K/Akt and
      PTEN that are crucial for physiological functions and the pathogenesis of
      multiple diseases.

PMID- 17222950
TI  - Cellular distribution of gamma-secretase subunit nicastrin in the developing and
      adult rat brains.
AB  - Nicastrin and presenilin 1 are integral components of the high molecular weight
      gamma-secretase complexes that regulate proteolytic processing of various type I
      membrane proteins including amyloid precursor protein and Notch. At present,
      there is little information regarding the cellular distribution of nicastrin in
      the developing or adult rat brain. We report here, using immunoblotting and
      immunohistochemical methods, that nicastrin in the adult rat brain is widely
      expressed and co-localized with presenilin 1 in select neuronal populations
      within all major areas, including the basal forebrain, striatum, cortex,
      hippocampus, amygdala, thalamus, hypothalamus, cerebellum and brainstem. We also
      observed dense neuropil labeling in many regions in the brain, suggesting that
      nicastrin gets transported to dendrites and/or axon terminals in the central
      nervous system. The levels of nicastrin are found to be relatively high at the
      early stages of postnatal development and then declined gradually to reach the
      adult profile. At the cellular level, nicastrin is localized predominantly in
      neuronal cell bodies at early postnatal stages, but is apparent both in cell
      bodies and dendrites/neuropil in all brain regions at the later stages. The
      regulation of nicastrin expression and localization during development and its
      distribution in a wide spectrum of neurons in the postnatal and adult rat brains
      provide an anatomical basis to suggest a multifunctional role for the gamma
      secretase complex in the developing and adult rat brains.

PMID- 17222951
TI  - A comparison of MRI, radiographic and clinical findings of the position of the
      TMJ articular disc following open treatment of condylar neck fractures.
AB  - We examined the position and function of the articular disc after open treatment
      of condylar fractures by comparing magnetic resonance images (MRI) and
      radiographs with clinical data. MRI and radiographs were taken after treatment of
      28 patients with 33 fractures of the mandibular condyles. In all cases, the disc
      was located in the fossa after open reduction and internal fixation (ORIF). The
      MRI, radiographic and clinical findings did not correlate, and damage to the
      temporomandibular joint (TMJ) could be seen more clearly on MRI than on clinical
      or radiographic examination. Damage to soft tissues seen on MRI after treatment
      was more pronounced in dislocated than in displaced fractures.

PMID- 17222952
TI  - Factors affecting the sagittal alignment of the lunate.
AB  - The lunate is described as having a tendency to rotate dorsally as a result of
      its wedge shape, with the apex towards the dorsum, but maintains an attitude of
      flexion in most individuals. The present study comprised CT scans of the wrist of
      70 healthy volunteers. Sagittal measurements were drawn for the midcarpal and
      radiocarpal axes, alignment and various shape patterns of the lunate. The
      midcarpal axis was found to be dorsal, volar and collinear to the radiocarpal
      axis in 21 (30%), 29 (41%) and 20 (29%) subjects, respectively. The sagittal
      alignment of the lunate demonstrated significant correlation with measurements of
      the midcarpal and radiocarpal axes with no correlation with its various shape
      patterns. It is concluded that the relationship between the midcarpal axis and
      the radiocarpal axis in terms of dorso-volar displacement has a key role in
      determining the sagittal alignment of the lunate, while the shape of the lunate
      may be only a secondary consideration.

PMID- 17222953
TI  - Primary giant cell tumours of the digital bones of the hand.
AB  - Primary giant cell tumours involving digital bones of the hand are rare lesions
      which are generally diagnosed at an advanced stage. Accurate diagnosis requires
      clinical evaluation, imaging studies and histopathological assessment.
      Conservative treatment by digit-sparing surgery is associated with high
      recurrence rates. In a ten year retrospective review, this study identified only
      four cases. Three cases involved a phalanx and were treated by distal amputation
      of the involved digit. None recurred. One involved the metacarpal and recurred
      twice following repeated curettage and bone grafting. No further recurrence has
      been detected after resection and replacement with a non-vascularised fibular
      graft and Silastic implant replacement of the metacarpophalangeal joint. Our
      small series of cases supports a policy of aggressive primary surgery, including
      amputation or en bloc resection and reconstruction.

PMID- 17222955
TI  - Health inequalities in Scotland and England: the contrasting journeys of ideas
      from research into policy.
AB  - Both the UK's Labour Government and Scotland's devolved Labour-Liberal Democrat
      coalition Executive have committed themselves to reducing health inequalities.
      Furthermore, both institutions have emphasised the importance of using evidence
      to inform policy responses. In light of such political commitments, a significant
      amount of work has been undertaken in the field of health inequalities in order
      to: (i) review the available research evidence; (ii) assess the extent to which
      policies have been based on this research evidence; and (iii) evaluate the
      success (or failure) of policies to tackle health inequalities. Yet so far only
      limited attention has been given to exploring how key actors involved in research
      policy dialogues understand the processes involved. In an attempt to address this
      gap, this article draws on data from semi-structured interviews with 58 key
      actors in the field of health inequalities research and policymaking in the UK to
      argue that it is ideas, rather than research evidence, which have travelled from
      research into policy. The descriptions of the varying journeys of these ideas fit
      three types--successful, partial and fractured--each of which is outlined with
      reference to one example. The paper then employs existing theories about research
      policy relations and the movement of ideas in an attempt to illuminate and better
      understand the contrasting journeys. In the concluding discussion, it is argued
      that the third approach, which focuses on the entrepreneurial processes involved
      in the marketing of ideas, is most helpful in understanding the research
      findings, but that this needs to be discussed in relation to the political
      context within which negotiations take place.

PMID- 17222956
TI  - Truncations of gelonin lead to a reduction in its cytotoxicity.
AB  - Gelonin is a single chain ribosome-inactivating protein (RIP) with potential
      applications as a bullet of immunoconjugate for the treatment of cancer and AIDS.
      Using truncated forms of gelonin, we now report the relationship between its
      conformation and function. Circular dichroism (CD) and fluorescence spectra show
      that the N-terminus forms beta-sheets whereas the C-terminus contains alpha
      helices of secondary structures. Biological experiments indicate that all gelonin
      truncation mutants lose partial toxicity compared to intact gelonin, an effect
      most strongly seen with C-terminally truncated gelonin. Similar evidence is also
      provided using a DNase-like activity assay. In addition, the intact gelonin
      exhibits the highest cytotoxicity to cancer cells. These results suggest that
      truncations of the terminal region of gelonin negatively regulate its function
      dominantly and that, due to its toxicity, intact gelonin is an important
      potential immunoconjugate.

PMID- 17222957
TI  - Resin strengthening of dental ceramics- the impact of surface texture and silane.
AB  - OBJECTIVES: To examine the effect of porcelain surface texture achieved utilising
      three clinically relevant surface preparation methods prior to silane and
      unfilled resin application on the flexure strength of a low fusing feldspathic
      porcelain. MATERIALS AND METHODS: Five hundred and forty dentine disc-shaped
      specimens (15.0mm diameter and 0.9mm thickness) were condensed, fired and
      allocated to 18 groups. Six groups were stored as-fired, six were alumina abraded
      and six were acid-etched. Samples were coated with silane, unfilled resin or both
      prior to bi-axial flexure testing. Group means were compared utilising a three
      factor design general linear model and post hoc all paired Tukey tests at P<0.05.
      Weibull analysis was employed to examine the reliability of the strength data.
      Profilometry was used to characterise the surface texture of the specimen
      surfaces. RESULTS: Alumina abraded and acid-etched specimens had significantly
      lower flexure strengths than the as-fired specimens. A significant difference
      between the degree of strengthening observed following unfilled resin application
      on the three surface texture investigated was observed (P<0.001). Silane
      application prior to resin coating resulted in no further significant increases
      in the mean bi-axial flexure strengths of the three surface textures. The as
      fired surfaces had a low frequency of irregular amplitude defects, alumina
      abraded surfaces had an increased frequency of regular amplitude defects whilst
      the acid-etched surface consisted of an increased frequency of irregular
      amplitude defects. CONCLUSION: The strengthening mechanism whilst dependent on
      surface texture was independent of defect severity. No significant strengthening
      occurred following silane priming suggesting that, for the unfilled resin
      utilised, the strengthening mechanism was not enhanced by improved resin-ceramic
      adhesion.

PMID- 17222958
TI  - Effect of a desensitizing agent containing glutaraldehyde and HEMA on bond
      strength to Er:YAG laser-irradiated dentine.
AB  - OBJECTIVES: The aim of this study was to investigate whether a desensitizing
      agent (GLUMA Desensitizer) containing glutaraldehyde and HEMA improved the bond
      strength and bonding durability of a self-etching primer adhesive to Er:YAG
      irradiated dentine. METHOD: Dentine of 120 human molars was exposed by wet
      grinding on SiC paper for bond strength testing. Thirty specimens each were
      allocated to the following treatment groups: (1) control; (2) Er:YAG laser
      irradiation; (3) Er:YAG laser irradiation followed by application of GLUMA
      Desensitizer; (4) Er:YAG laser irradiation followed by application of GLUMA
      Desensitizer and 10s rinsing with water. Composite cylinders were bonded to the
      dentine surfaces with a self-etching priming adhesive system. Tensile bond
      strengths (TBS) of 10 specimens of each treatment group were measured after 24-h
      water storage, 6 months water storage and 12 months water storage, respectively,
      and the failure modes were analyzed. TBS data were statistically treated by two
      way ANOVA and Fisher's PLSD test at a significance level of p<0.05. RESULTS: TBSs
      for the GLUMA-non rinse and GLUMA-rinse groups were significantly higher than for
      the laser group at 24 h and 12 months. Specimens from the Er:YAG-irradiated
      dentine group had significantly lower bond strengths than the control group at
      each storage time. All control specimens showed cohesive fractures in resin close
      to the bonding interface whereas the Er:YAG laser-irradiated groups showed both
      dentine cohesive, resin cohesive and dentine-resin mixed failures. CONCLUSION:
      Application of GLUMA Desensitizer to Er:YAG-irradiated dentine increases the bond
      strength and durability of the self-etching priming adhesive used.

PMID- 17222959
TI  - Brain regions and genes affecting postural control.
AB  - Postural control is integrated in all facets of motor commands. The role of
      cortico-subcortical pathways underlying postural control, including cerebellum
      and its afferents (climbing, mossy, and noradrenergic fibers), basal ganglia,
      motor thalamus, and parieto-frontal neocortex has been identified in animal
      models, notably through the brain lesion technique in rats and in mice with
      spontaneous and induced mutations. These studies are complemented by analyses of
      the factors underlying postural deficiencies in patients with cerebellar atrophy.
      With the gene deletion technique in mice, specific genes expressed in cerebellum
      encoding glutamate receptors (Grid2 and Grm1) and other molecules (Prkcc, Cntn6,
      Klf9, Syt4, and En2) have also been shown to affect postural control. In
      addition, transgenic mouse models of the synucleinopathies and of Huntington's
      disease cause deficiencies of motor coordination resembling those of patients
      with basal ganglia damage.

PMID- 17222960
TI  - Combination of multispectral remote sensing, variable rate technology and
      environmental modeling for citrus pest management.
AB  - The Lower Rio Grande Valley (LRGV) of south Texas is an agriculturally rich area
      supporting intensive production of vegetables, fruits, grain sorghum, and cotton.
      Modern agricultural practices involve the combined use of irrigation with the
      application of large amounts of agrochemicals to maximize crop yields. Intensive
      agricultural activities in past decades might have caused potential contamination
      of soil, surface water, and groundwater due to leaching of pesticides in the
      vadose zone. In an effort to promote precision farming in citrus production, this
      paper aims at developing an airborne multispectral technique for identifying tree
      health problems in a citrus grove that can be combined with variable rate
      technology (VRT) for required pesticide application and environmental modeling
      for assessment of pollution prevention. An unsupervised linear unmixing method
      was applied to classify the image for the grove and quantify the symptom severity
      for appropriate infection control. The PRZM-3 model was used to estimate
      environmental impacts that contribute to nonpoint source pollution with and
      without the use of multispectral remote sensing and VRT. Research findings using
      site-specific environmental assessment clearly indicate that combination of
      remote sensing and VRT may result in benefit to the environment by reducing the
      nonpoint source pollution by 92.15%. Overall, this study demonstrates the
      potential of precision farming for citrus production in the nexus of industrial
      ecology and agricultural sustainability.

PMID- 17222961
TI  - A new postoperative predictor of time to urinary continence after laparoscopic
      radical prostatectomy: the urine loss ratio.
AB  - OBJECTIVES: To assess the correlation of a newly defined parameter, "urine loss
      ratio" (ULR), with the time to continence and probability for incontinence after
      laparoscopic radical prostatectomy (LRP). MATERIALS AND METHODS: A standardized
      "micturition protocol" that uses 24-h pad testing to objectively quantify urine
      loss after removal of the catheter was obtained from 939 patients who underwent
      LRP and were provided complete follow-up regarding continence. ULR was defined as
      the weight of urine loss in the pad divided by daily micturition volume,
      distinguishing between ULR on the first day after catheter removal and the last
      day of hospital stay. The time to continence was classified as early (0-3 mo),
      midterm (4-12 mo), and late continence (13-24 mo). RESULTS: Early continence was
      attained in 69.8% (n=655) of patients, midterm continence in 18.4% (n=173), and
      late continence in 3.5% (n=33). Of 939 patients in whom first-day ULR was
      quantified, 495 patients were not discharged immediately and their last-day ULR
      was quantified (2.3 d following catheter removal). There was a linear correlation
      between time to continence and ULR, which was more significant for last- than
      first-day ULR (p<0.001). A cutoff point of more than 15% of urine loss indicates
      a high risk of incontinence (ie, 8-fold for first-day ULR, 55-fold for last-day
      ULR). CONCLUSION: ULR predicts the time to continence and may be used to select
      patients for specific rehabilitation programs and early adjuvant medical therapy,
      particularly when urine loss exceeds 15%.

PMID- 17222962
TI  - Cytochrome P450 side-chain cleavage: insights gained from homology modeling.
AB  - Cytochrome P450 side-chain cleavage (CYP11A1) catalyzes the conversion of
      cholesterol to pregnenolone, the first step in steroidogenesis. The absence of a
      solved crystal structure has complicated deductions pertaining to the
      structure/function relationships of this key enzyme. Although a number of
      techniques have been employed to identify domains and specific amino acid
      residues important for catalytic activity, these methods have been unsuccessful
      in predicting three-dimensional orientations in space and thus the mechanism by
      which they exert their kinetic effect. This review aims to demonstrate the
      significant contribution homology modelling, when employed as a tool in
      combination with other standard biochemical techniques, has made towards our
      understanding of CYP11A1.

PMID- 17222963
TI  - Cofactors, redox state, and directional preferences of hydroxysteroid
      dehydrogenases.
AB  - The hydroxysteroid dehydrogenases (HSDs) interconvert pairs of weak and potent
      steroids, thus serving as key enzymes in the regulation of intracellular hormone
      potency. These enzymes may appear to drive unidirectional steroid flux in intact
      cells but actually catalyze bi-directional metabolism that achieve pseudo
      equilibria with strong directional preferences. Even small shifts in the
      magnitude of these pseudo-equilibria can profoundly change steroid potency and
      thus contribute to disease. Consequently, we are studying the structural and
      biochemical principles that govern these directional preferences and the
      resilience of these pseudo-equilibria in intact cells. HSD directional
      preferences in intact cells are governed largely by relative affinities for
      nicotinamide cofactors [NAD(P)(H)] and existing cofactor gradients. We can
      attenuate the directional preferences for human 17betaHSD type 1 and rat AKR1C9
      in intact cells by either diminishing the NADPH/NADP(+) gradient or by mutating
      the arginine residues that form salt bridges with the 2'-phosphate of NADP(H)
      (R38 and R276, respectively).

PMID- 17222964
TI  - Glioblastoma with an intratumoral feeding-artery aneurysm.
AB  - We report a patient with recurrent glioblastoma, in whom serial magnetic
      resonance angiography (MRA) demonstrated gradual enlargement of an artery feeding
      the tumor and the development of an intratumoral aneurysm that led to
      intratumoral hemorrhage. The literature contains no previous reports that
      clinically document intratumoral aneurysms arising from these vessels. This is a
      rare case of glioblastoma in which the association of an intratumoral feeding
      artery aneurysm, whose rupture led to intratumoral bleeding, was documented by
      serial MRA imaging and follow-up.

PMID- 17222965
TI  - The decolorization and mineralization of acid orange 6 azo dye in aqueous
      solution by advanced oxidation processes: a comparative study.
AB  - The comparison of different advanced oxidation processes (AOPs), i.e. ultraviolet
      (UV)/TiO(2), O(3), O(3)/UV, O(3)/UV/TiO(2), Fenton and electrocoagulation (EC),
      is of interest to determine the best removal performance for the destruction of
      the target compound in an Acid Orange 6 (AO6) solution, exploring the most
      efficient experimental conditions as well; on the other hand, the results may
      provide baseline information of the combination of different AOPs in treating
      industrial wastewater. The following conclusions can be drawn: (1) in the effects
      of individual and combined ozonation and photocatalytic UV irradiation, both
      O(3)/UV and O(3)/UV/TiO(2) processes exhibit remarkable TOC removal capability
      that can achieve a 65% removal efficiency at pH 7 and O(3) dose=45mg/L; (2) the
      optimum pH and ratio of [H(2)O(2)]/[Fe(2+)] found for the Fenton process, are pH
      4 and [H(2)O(2)]/[Fe(2+)]=6.58. The optimum [H(2)O(2)] and [Fe(2+)] under the
      same HF value are 58.82 and 8.93mM, respectively; (3) the optimum applied voltage
      found in the EC experiment is 80V, and the initial pH will affect the AO6 and TOC
      removal rates in that acidic conditions may be favorable for a higher removal
      rate; (4) the AO6 decolorization rate ranking was obtained in the order of
      O(3)<O(3)/UV=O(3)/UV/TiO(2)<EC<Fenton; (5) the ranking of TOC removal efficiency
      of selected AOPs was in the order of O(3)=Fenton<EC<O(3)/UV<O(3)/UV/TiO(2) for
      30min of reaction time.

PMID- 17222966
TI  - Microcolumn studies of dye adsorption onto manganese oxides modified diatomite.
AB  - The method described here cannot fully replace the analysis of large columns by
      small test columns (microcolumns). The procedure, however, is suitable for
      speeding up the determination of adsorption parameters of dye onto the adsorbent
      and for speeding up the initial screening of a large adsorbent collection that
      can be tedious if a several adsorbents and adsorption conditions must be tested.
      The performance of methylene blue (MB), a basic dye, Cibacron reactive black (RB)
      and Cibacron reactive yellow (RY) was predicted in this way and the influence of
      initial dye concentration and other adsorption conditions on the adsorption
      behaviour were demonstrated. On the basis of the experimental results, it can be
      concluded that the adsorption of RY onto manganese oxides modified diatomite
      (MOMD) exhibited a characteristic "S" shape and can be simulated effectively by
      the Thomas model. It is shown that the adsorption capacity increased as the
      initial dye concentration increased. The increase in the dye uptake capacity with
      the increase of the adsorbent mass in the column was due to the increase in the
      surface area of adsorbent, which provided more binding sites for the adsorption.
      It is shown that the use of high flow rates reduced the time that RY in the
      solution is in contact with the MOMD, thus allowing less time for adsorption to
      occur, leading to an early breakthrough of RY. A rapid decrease in the column
      adsorption capacity with an increase in particle size with an average 56%
      reduction in capacity resulting from an increase in the particle size from 106
      250 microm to 250-500 microm. The experimental data correlated well with
      calculated data using the Thomas equation and the bed depth-service time (BDST)
      equation. Therefore, it might be concluded that the Thomas equation and the BDST
      equations can produce accurate predication for variation of dye concentration,
      mass of the adsorbent, flow rate and particle size. In general, the values of
      adsorption isotherm capacity obtained in a batch system show the maximum values
      and are considerably higher than those obtained in a fixed-bed.

PMID- 17222967
TI  - Co-landfilling of pretreated waste: disposal and management strategies at lab
      scale.
AB  - The present paper deals with the possible advantages that can be obtained by co
      landfilling of municipal solid waste organic fraction (MSWOF) and bottom ash (BA)
      from the incineration of municipal solid waste. In particular, the aim of the
      research hereby presented is to check the effect exerted by different disposal
      (mixed or layered) and management strategies (anaerobic or semiaerobic
      conditions) for landfills in which MSWOF and BA are co-disposed. Three lab-scale
      reactors were set-up: the reactor A with mixed BA and MSWOF in anaerobic
      conditions, the reactor B with mixed BA and MSWOF in semiaerobic conditions, the
      reactor C with layered BA and MSWOF in anaerobic conditions. The results obtained
      showed that the aeration at the beginning of the experimental period for about 60
      days led to a more rapid biodegradation of the organic matter and to an improved
      leachate quality in terms of both organic load and nitrogen content. Also a
      significant increase in the settling rate was observed at the end of the aeration
      phase. Therefore, the aerobic management can be advised as the most available
      strategy providing a more rapid biological and mechanical stabilization of the
      bulk waste. Otherwise, the disposal strategy did not exert any significant effect
      on the leachate characteristics; however, the layered configuration may be
      adopted in order to accelerate the main settlements.

PMID- 17222968
TI  - A multi-element solid-phase extraction method for trace metals determination in
      environmental samples on Amberlite XAD-2000.
AB  - A method for the preconcentration of some transition elements at trace level was
      proposed using a column filled with Amberlite XAD-2000 resin. Metal ions were
      adsorbed on XAD-2000 as their diethyldithiocarbamate chelates, then analytes
      retained on the resin were eluted by 1 mol L(-1) nitric acid in acetone and
      determined by flame atomic absorption spectrometry (FAAS). The influences of some
      analytical parameters including pH of sample solution, ligand amount, the type,
      concentration and volume of elution solution, flow rates of the sample and eluent
      solutions, adsorption capacity of the resin and sample volume on the
      preconcentration efficiency have been investigated. The influences of some matrix
      elements were also examined. The detection limit (N=20, 3 sigma) for Mn(II),
      Fe(II), Co(II), Cu(II), Cd(II), Zn(II), Pb(II) and Ni(II) were found as 0.20,
      0.35, 0.25, 0.20, 0.20, 0.15, 0.45 and 0.25 microg L(-1), respectively. The
      validation of the procedure was carried out by analysis of certified reference
      materials. The proposed method was applied to natural waters and kale vegetable
      (Brassica oleracea var. acephala).

PMID- 17222969
TI  - Mass transfer, kinetics and equilibrium studies for the biosorption of methylene
      blue using Paspalum notatum.
AB  - Batch experiments were carried out for the sorption of methylene blue onto
      Paspalum notatum. The operating variables studied were initial dye concentration,
      initial solution pH, adsorbent dosage and contact time. Experimental equilibrium
      data were fitted to Freundlich, Langmuir and Redlich-Peterson isotherms by non
      linear regression method. Six error functions was used to determine the optimum
      isotherm by non-linear regression method. The present study shows r2 as the best
      error function to determine the parameters involved in both two- and three
      parameter isotherms. Langmuir isotherm was found to be the optimum isotherm for
      methylene blue onto P. notatum. The monolayer methylene blue sorption capacity of
      P. notatum was found to be 31 mg/g. The kinetics of methylene blue onto P.
      notatum was found to follow a pseudo second order kinetics. A Boyd plot confirms
      the external mass transfer as the rate-limiting step in the dye sorption process.
      The influence of initial dye concentration on the dye sorption process was
      represented in the form of dimensionless mass transfer numbers (Sh/Sc0.33) and
      was found to vary as C(0)-5x10(-6).

PMID- 17222970
TI  - Particle size distributions of oil mists in workplace atmospheres and their
      exposure concentrations to workers in a fastener manufacturing industry.
AB  - This study was set out to characterize size distributions of oil mists in three
      workplace atmospheres of the forming, threading, and heat treatment in a fastener
      manufacturing industry and to assess their exposures to workers. Particle size
      segregating samplings were conducted on the workplace atmospheres of the three
      selected industrial processes by using the modified Marple 8-stage cascade
      impactor (m-Marple). We found that mass median aerodynamic diameter (MMAD) of the
      fine mode and coarse mode fell to the range 0.309-0.501 microm and 8.16-13.0
      microm, respectively. The fractions of inhaled particles exposed to different
      regions of the respiratory tracts found that the alveolar region was consistently
      higher than both head and tracheobronchial regions in all three studied exposure
      groups. Personal inhalable oil mist samplings were conducted on workers in the
      three selected processes revealed their exposure levels as: threading workers
      (2.11 mg/m3)>forming workers (1.58 mg/m3)>heat treatment workers (0.0801 mg/m3).
      The estimated respirable exposure concentrations for both forming and threading
      workers (1.34 mg/m3 and 1.40 mg/m3, respectively) were higher than the level
      known for "increased risk of pulmonary injury" (0.20 mg/m3) suggesting that
      appropriate control measures should be taken to reduce their exposures to the oil
      mists of the respirable fraction immediately.

PMID- 17222971
TI  - Chromium fractionation in semi-arid soils amended with chromium and tannery
      sludge.
AB  - We studied Cr fractionation in three semi-arid soils (cultivated, under-the
      canopy, and outside-the-canopy soils). The soils were amended with: Cr3+, Cr6+,
      tannery sludge, Cr3++tannery sludge, and Cr6++tannery sludge and all soils were
      incubated for 30 and 120 days at 25 degrees C. The Cr in three semi-arid soils
      was fractionated using sequential extraction (Tessier scheme). Data of Cr
      fractionation were used to find the correlations with microbial activities
      determined in previous work. The microbial activities: CO2-C evolved,
      dehydrogenase activity and nitrification were determined in the same soils
      amended with the same treatments. Tannery sludge was added at 0.0125 g g(-1) soil
      and Cr3+ or Cr6+ at 250 microg g(-1) soils. After 120 days of incubation, higher
      values of concentration of Cr were found in the residual fraction in the three
      soils amended with all the treatments, except cultivated and outside-the-canopy
      soils amended with Cr6++tannery. The non-residual fraction tended to decrease
      with time except in cultivated and outside-the-canopy soils amended with
      Cr6++tannery sludge. CO2-C evolved was significantly correlated (p<0.05 and
      p<0.001) with fractions bound to: Mn oxides, Fe oxides organic matter at 30 and
      120 days of incubation (from r=0.827 to 0.979). Dehydrogenase activity was
      correlated with fractions bound to Fe oxides and bound to organic matter, and
      nitrification with fraction bound to organic matter at 30 days of incubation
      (r=0.874, 0.959, and 0.803, respectively). These results suggest that even in a
      sparingly available Cr fraction in semi-arid soils has effect on microbial
      activities.

PMID- 17222972
TI  - TNF-alpha involves in altered prefrontal synaptic transmission in mice with
      persistent inflammatory pain.
AB  - Tumor necrosis factor alpha (TNF-alpha) is implicated in the development of
      persistent pain. Its expression increases both spinally and supraspinally after
      peripheral inflammation. The anterior cingulate cortex (ACC) is a forebrain
      structure known for its roles in pain transmission and modulation. Prefrontal
      synaptic transmission is potentiated in mice with chronic pain through an
      enhancement of presynaptic transmitter release. However, it is not known if TNF
      alpha expression is altered in the ACC in response to persistent pain and if
      synaptic transmission within this region is modulated by TNF-alpha. In the
      present study, we examined TNF-alpha expression in the mouse ACC following hind
      paw administration of complete Freund's adjuvant (CFA) and examined the role of
      TNF-alpha in ACC synaptic transmission. Quantification of TNF-alpha at the
      protein level (by ELISA) revealed enhanced expression following CFA-induced
      peripheral inflammation. In vitro whole-cell patch-clamp recordings revealed that
      TNF-alpha significantly enhanced synaptic transmission through increased
      probability of neurotransmitter release in the ACC. Our findings provide evidence
      that presynaptic alterations caused by peripheral inflammation is partly
      attributable to the up-regulation of TNF-alpha in the ACC.

PMID- 17222973
TI  - Gap junction hemichannel-mediated release of glutathione from cultured rat
      astrocytes.
AB  - Release of glutathione (GSH) from astrocytes is essential for the supply of
      neurons with the GSH precursor cysteine. In order to test whether gap junction
      hemichannels could contribute to GSH release from astrocytes, we incubated
      astrocyte-rich primary cultures from neonatal rat brain in the absence of
      divalent cations, a condition that is known to increase the opening probability
      of hemichannels. During incubation in divalent cation free incubation solution
      (DCFS) the cells remained viable and released about 50% of the initial cellular
      GSH within 15 min. This extracellular GSH accumulation in DCFS was lowered by the
      presence of Ca2+ in a concentration dependent manner with a half-maximal
      inhibition at a Ca2+ concentration of 107+/-46 microM. Extracellular GSH
      accumulation in DCFS was also blocked by the divalent cations Mg2+, Ba2+ and Sr2+
      as well as by the known gap junction inhibitors carbenoxolone (CBX), flufenamic
      acid (FFA) and lanthanum chloride. In contrast, the P2X7 receptor blocker
      brilliant blue G (BBG) did not affect GSH release in divalent cation free
      solution. This pharmacological profile strongly suggests that astrocytes are able
      to release GSH via open hemichannels. This release of GSH may have severe
      consequences for the antioxidative defense and for the GSH homeostasis in
      pathological brain.

PMID- 17222975
TI  - A confirmation of Rexed's laminar hypothesis using the Sholl linear method
      complemented by nonparametric statistics.
AB  - Images of Golgi-impregnated neurons from laminae I to VI in the dorsal horn of
      the cat spinal cord were subjected to the linear Sholl analysis of concentric
      circles to support Rexed's hypothesis on the laminar organization of spinal gray
      matter in mammals. Since Rexed's determination of the laminae is based upon size,
      location, and grouping of cell bodies, neglecting one of the principal
      morphologic attributes of the neuron-the dendritic tree, the purpose of the
      present study was to evaluate Rexed's hypothesis testing the structure of
      dendritic arborization patterns of neurons. The differences in the complexity of
      dendritic trees between the groups of neurons from different laminae were
      evaluated by nonparametric statistics. Data obtained using Sholl's method is not
      always subjected to complete statistical analysis. The problem becomes
      particularly apparent in the quantitative examination of dendritic structures.
      Our aim was also to perform a careful analysis of our data for normality, in
      order to choose the appropriate statistical method for data processing. In the
      linear Sholl analysis, it is important to properly represent and interpret the
      frequency functions. The objective of this study was also to investigate the
      problems of determining the frequency functions, plotting the corresponding lines
      of regression, and measuring the degree of fluctuation of experimental data
      points around these lines. The main result of our testing is a confirmation of
      Rexed's laminar scheme: we have proved that there are 6 out of 10 possible pairs
      of samples where one member significantly differs from the other, i.e. one lamina
      is significantly distinguishable from the other.

PMID- 17222974
TI  - Eye field requires the function of Sfrp1 as a Wnt antagonist.
AB  - Wnts have been shown to provide a posteriorizing signal that has to be repressed
      in the specification of vertebrate forebrain region. Previous studies have shown
      that Wnt activation by LiCl treatment causes an expansion of optic stalk and mid
      hindbrain boundary, whereas eye and ventral diencephalon in the forebrain region
      were reduced. However, the molecular mechanism, by which inhibits Wnt activity in
      the forebrain remains poorly defined. To investigate relationship between
      forebrain specification and Wnt signaling, the zebrafish homologue of secreted
      frizzled related protein1 (sfrp1) has been characterized. The transcripts of
      sfrp1 are detected in the presumptive forebrain at gastrula and in the ventral
      telencephalon, ventral diencephalon, midbrain and optic vesicles at 24h after
      postfertilization (hpf). Overexpression of sfrp1 causes an anteriorization of
      embryo, with enlarged head and reduced posterior structure as in the embryo
      overexpressing dominant-negative form of Frizzled8a or Dkk1. Its overexpression
      restored the eye defects in the Wnt8b-overexpressing embryos, but not in the LiCl
      treated embryos. These results suggest that Sfrp1 expressed in the forebrain and
      eye field plays a critical role in the extracellular events of antagonizing Wnt
      activity for the forebrain specification.

PMID- 17222976
TI  - Crystal structure refinement using Bloch-wave method for precession electron
      diffraction.
AB  - Procedure for crystal structure refinement using precession electron diffraction
      data and Bloch-wave method for accounting multibeam scattering is described.
      Refinement procedure takes into account features of precession geometry. Refining
      model consists of structural and reduced parameters determining dynamic
      diffraction. Difference between measured and calculated dynamic intensities of
      reflections is minimized with application of a nonlinear least squares method. As
      test example we used Si single nanocrystals. The influence of the reduced
      parameters on the quality of the obtained model is discussed. Refinement
      procedure is a part of ASTRA software.

PMID- 17222977
TI  - A case of severe smoke inhalation injury without cutaneous burn required massive
      fluid for resuscitation.

PMID- 17222978
TI  - Resuscitation burn card--a useful tool for burn injury assessment.
AB  - It is well recognised that the initial assessment of body surface area affected
      by a burn is often over estimated in Accident and Emergency Departments. A useful
      aide-memoir in the acute setting is Wallace's "rule of nines" or using the
      patients' palmar surface of the hand, which approximates 1% of the total body
      surface area, as a method of assessment. Unfortunately, as with every system,
      limitations apply. Factors such as patient size and the interpretation of what is
      exactly the 'palmar surface' may significantly influence burn size estimations
      and subsequently fluid resuscitation. Our aim is to develop a simple, quick and
      easy reproducible method of calculating burn injuries for medical professionals
      in the acute setting. Worldwide, the dimensions of a credit card are standardized
      (8.5 cm x 5.3 cm), thus producing a surface area of 45 cm2. We created a
      resuscitation burn card (RBC) using these exact same proportions, upon which a
      modified body surface area (BSA) nomogram was printed. Knowing the patient height
      and weight, we calculated the surface area of the card as percentage of total
      body surface area (TBSA). On the opposite site of the RBC, a Lund and Browder
      chart was printed, as well as the Parkland formula and a formula to calculate
      paediatric burn fluid requirements. The plastic, flexible RBC conformed well to
      the body contour and was designed for single use. We used the resuscitation burn
      card in the initial assessment of simulated burns in a Regional Burn Centre and
      in an Accident and Emergency Department. The information present on the card was
      found to be clear and straightforward to use. The evaluation of burn extent was
      found to be more accurately measured than the estimation obtained without the
      RBC. The resuscitation burn card can be a valuable tool in the hands of less
      experienced medical professionals for the early assessment and fluid
      resuscitation of a burn.

PMID- 17222979
TI  - Camphor burns to the palm: an unusual self-inflicted burn.

PMID- 17222980
TI  - The use of laser doppler imaging for burn depth assessment after application of
      flammacerium.

PMID- 17222981
TI  - Common cancers in adolescents.
AB  - Adolescence, spanning 15-19 years of age, is a time of developmental transition
      from childhood to adult life. The spectrum of cancers affecting this age group
      reflects a similar transition. The common malignant diseases of childhood -
      leukemias, lymphomas, tumors of the central nervous system and embryonal solid
      tumors (such as nephroblastoma and neuroblastoma) - are replaced in relative
      frequency by sarcomas of bone and soft tissue, and tumors of the male and female
      genital tracts. Moreover, the epithelial tumors (carcinomas), so prevalent in
      adults, occur (albeit at much lower frequencies) in adolescents. Within
      individual tumor types, biological features may be distinctive in this age group.
      Examples are the high prevalence of poor prognostic determinants in acute
      lymphoblastic leukemia and histologically higher grade forms of astrocytic/glial
      tumors. Particular challenges in addressing the common tumors of adolescence
      include the development of better categorization, especially of soft tissue
      sarcomas, and exploring these diseases in this age group within the developing
      world where most adolescents reside.

PMID- 17222982
TI  - Voltage-gated potassium conductances in Gymnotus electrocytes(AB).
AB  - Electrocytes are muscle-derived cells that generate the electric organ discharge
      (EOD) in most gymnotiform fish. We used an in vitro preparation to determine if
      the complex EOD of Gymnotus carapo was related to the membrane properties of
      electrocytes. We discovered that in addition to the three Na(+)-mediated
      conductances described in a recent paper [Sierra F, Comas V, Buno W, Macadar O
      (2005) Sodium-dependent plateau potentials in electrocytes of the electric fish
      Gymnotus carapo. J Comp Physiol A 191:1-11] there were four K(+)-dependent
      conductances. Membrane depolarization activated a delayed rectifier (I(K)) and an
      A-type (I(A)) current. I(A) displayed fast voltage-dependent activation
      inactivation kinetics, was blocked by 4-aminopyridine (1 mM) and played a major
      role in action potential (AP) repolarization. Its voltage dependence and kinetics
      shape the brief AP that typifies Gymnotus electrocytes. The I(K) activated by
      depolarization contributed less to AP repolarization. Membrane hyperpolarization
      uncovered two inward rectifiers (IR1 and IR2) with voltage dependence and
      kinetics that correspond to the complex "hyperpolarizing responses" (HRs)
      described under current-clamp. IR1 shows "instantaneous" activation, is blocked
      by Ba(2+) and Cs(+) and displays a voltage and time dependent inactivation that
      matches the hyperpolarizing phase of the HR. The activation of IR2 is slower and
      at more negative potentials than IR1 and is resistant to Ba(2+) and Cs(+). This
      current fits the depolarizing phase of the HR. The EOD waveform of Gymnotus
      carapo is more complex than that of other gymnotiform fish species, the
      complexity originates in the voltage responses generated through the interactions
      of three Na(+) and four K(+) voltage- and time-dependent conductances although
      the innervation pattern also contributes [Trujillo-Cenoz O, Echague JA (1989)
      Waveform generation of the electric organ discharge in Gymnotus carapo. I.
      Morphology and innervation of the electric organ. J Comp Physiol A 165:343-351].

PMID- 17222983
TI  - Hypobaric hypoxia-induced dendritic atrophy of hippocampal neurons is associated
      with cognitive impairment in adult rats.
AB  - Simulated hypobaric hypoxia (HBH), resembling high altitude hypoxia severely
      affects the CNS and results in several physiological changes. The hippocampus is
      closely associated with learning and memory and an insult to this region affects
      cognition. Previous studies suggest that rapid or prolonged exposures to HBH are
      associated with psychomotor and cognitive impairments. The defense personnel,
      mountain climbers and rescue teams are exposed to such harsh environment and thus
      it demands a systematic study emphasizing the subtle effects of such extreme
      environments on cognitive function. Accordingly, this study evaluated the effect
      of hypobaric hypoxia on structural changes in the principal neurons of the
      hippocampus and learning in eight-arm radial maze. Adult male Wistar rats,
      subjected to simulated hypobaric hypoxia equivalent to an altitude of 6000 m for
      a period of 2 or 7 days, in a hypoxic chamber served as hypoxic group (HY). Rats
      housed in a similar chamber for the same period of time, without hypoxic exposure
      served as sham control (SC), while normal control (NC) group of rats were housed
      in standard laboratory conditions. The dendritic morphology of neurons in cornu
      ammonis region 1 (CA1) and cornu ammonis region 3 (CA3) was studied in Golgi
      impregnated hippocampal sections. Exposure for 2 days to hypobaric hypoxia had
      minimal deleterious effects on the CA1 pyramidal neurons, while exposure for 7
      days resulted in a significant decrease in the number of branching points,
      intersections and dendritic length. Unlike the CA1 pyramidal neurons, the CA3
      neurons exhibited dendritic atrophy following both 2 and 7 days of hypoxic
      exposure. Further, hippocampal-dependent spatial learning was affected marginally
      following 2 day exposure, while 7 day exposure severely affected learning of the
      partially baited radial arm maze task. Our study suggests that dendritic atrophy
      in the hippocampus on exposure to HBH could be one of the bases for the cognitive
      deficits exhibited under such conditions.

PMID- 17222984
TI  - Changes in brain oxidative metabolism induced by water maze training.
AB  - Although the hippocampus has been shown to be essential for spatial memory, the
      contribution of associated brain regions is not well established. Wistar rats
      were trained to find a hidden escape platform in the water maze during eight
      days. Following training, the oxidative metabolism in different brain regions was
      evaluated using cytochrome oxidase histochemistry. Metabolic activations were
      found in the prelimbic cortex, cornu ammonis (CA) 1 subfield of the dorsal
      hippocampus and the anterior thalamic nuclei, relative to yoked swim controls and
      naive rats. In addition, many cross-correlations in brain metabolism were
      observed among the latter regions. These results support the implication of a
      hippocampal-prefrontal-thalamic system to spatial memory in rats.

PMID- 17222985
TI  - The serotonin transporter gene and alcoholism: the two pathways to suicidal
      behavior.

PMID- 17222986
TI  - Scrotal pouch as a urinary reservoir: a surgical revolution or bizarre
      hypothesis?

PMID- 17222987
TI  - A pathogenetic mechanism for COX-2 inhibitor-induced cardiovascular events
      proposed to be useful in structuring medical testimony in rofecoxib trials.
AB  - In this communication, a pathogenetic mechanism for COX-2 inhibitor (coxib)
      induced cardiovascular events, especially myocardial infarction, will be
      discussed. This mechanism is proposed to be useful in structuring medical
      testimony in rofecoxib trials, and specific principles for separating rofecoxib
      induced infarctions from the overall group of rofecoxib-related infarctions will
      be outlined. The proposed mechanism is based on the principles of the altered
      homeostatic theory, whose basic positions will be summarized. Coxib-induced
      infarctions apparently have been considered to be "special" infarctions because
      they generally are attributed to thromboxane rather than to dyslipidemia.
      However, it is asserted that coxib-induced infarctions basically are "regular"
      infarctions because the risk of thromboxane is basically the same as the risk of
      multiple and diverse "regular" risk factors. Both coxibs and "regular" risk
      factors are considered to express thrombosis/vasoconstriction, and it is this
      expression which makes coxib-induced infarctions basically "regular" infarctions.
      Thrombosis/vasoconstriction is crucial to the induction of myocardial infarction;
      thrombosis is the accepted and spasm (of resistance vessels) is a proposed
      mechanism for infarction. It also is asserted that coxib-induced infarctions have
      a significant load of "regular" risk factors, and that the risk of coxibs adds to
      the risk of "regular" risk factors. The combination of a significant load of
      "regular" risk factors plus the risk of coxibs is considered necessary to cause a
      coxib-induced infarction. It will be difficult to separate out with surety many,
      if not most, cases of rofecoxib-induced infarctions; this is because of the
      difficulty in assessing the risk imposed by "regular" risk factors vis-a-vis the
      risk of rofecoxib, and specific problems in separation will be discussed.
      However, reasonably, infarctions with a short time-to-event tend to be rofecoxib
      induced; infarctions which closely follow a new risk factor, as loss of spouse or
      stress, would rather automatically be attributed to the new risk factor. It then
      follows that infarctions with a long time-to-event tend to be non-rofecoxib
      induced. Additionally, and contrary to past practice, infarctions cannot be
      designated as non-rofecoxib-induced infarctions because of the presence of a
      significant load of "regular" risk factors; after all, rofecoxib-induced
      infarctions reasonably are associated with a significant load of such risk
      factors.

PMID- 17222988
TI  - Is diabetes mellitus a risk factor or a protector for primary open angle
      glaucoma?

PMID- 17222989
TI  - Topical estrogen drops may be a new alternative in the treatment of glaucoma.

PMID- 17222990
TI  - The plateau iris component of primary angle closure glaucoma: developmental or
      acquired.
AB  - Primary angle closure glaucoma has been called the most common form of glaucoma
      in the world, and the leading cause of bilateral blindness. Pupillary block is
      felt to be the main mechanism of outflow obstruction in this condition. Recent
      advances in morphologic assessment of angle closure, specifically by means of
      ultrasound biomicroscopy, have revealed that plateau iris in eyes with angle
      closure glaucoma is more common than had previously been thought. The most
      characteristic finding in this disease is thicker and more anteriorly positioned
      lens. This induces the pupillary block that relives by laser iridotomy. Residual
      angle closure after laser iridotomy is due to the plateau iris. Peripheral
      iridoplasty, the standard treatment of plateau iris, tights the peripheral iris
      and opens the angle but has no effect on the ciliary processes configuration. The
      ciliary processes are positioned posteriorly after lens extraction but dose not
      disappears completely. Considering these facts we hypothesized that the plateau
      iris in primary angle closure glaucoma is a developmental entity that reaches to
      a critical stage with aging owing to the thickening and forward movement of the
      lens. Cataract surgery deeps the anterior chamber, widens the irido-corneal angle
      and reposits the ciliary processes posteriorly, so it can prevents synechia
      formation and progressive lens-induced angle narrowing and plateau iris
      progression, the acquired component, with aging.

PMID- 17222991
TI  - Amphetamine affects the start of responding in the peak interval timing task.
AB  - In this paper we investigate how amphetamine affects performance in a PI task by
      comparing two analyses of responding during peak trials. After training on 24 s
      fixed interval (FI-24) with 96 s peak trials, rats were given amphetamine for 4
      consecutive days at doses of .5 and 1.0 mg/kg. Responses during peak trials were
      fitted with a Gaussian distribution to estimate the expected time of
      reinforcement from the peak time. A single trials analysis was also performed to
      determine the start time and stop time of the transition into and out of a high
      rate of responding on each peak trial. Amphetamine significantly decreased peak
      times as measured with the Gaussian curve fitting. However, in the single trials
      analysis, animals initiated responding significantly earlier, but did not stop
      responding earlier. Thus, fitting a Gaussian to the average performance across
      trials sometimes provides a different characterization of the timing process than
      does analyzing the start and stop of responding on individual trials. In the
      current experiment, the latter approach provided a more precise characterization
      of the effects of amphetamine on response timing.

PMID- 17222992
TI  - Inhibitor-free DNA for real-time PCR analysis of synovial fluid from horses,
      cattle and pigs.
AB  - The potential of five different commercial DNA isolation methods to remove real
      time PCR inhibitors from the synovial fluid of horses, cattle and pigs was
      investigated. All kits with the exception of one included a silica column-based
      purification of the DNA. With the fifth kit, DNA purification is achieved by
      removing contaminating macromolecules by a desalting process. We used a recently
      developed method based on comparison of the real-time PCR signal of an artificial
      target incorporated into each PCR reaction in the presence of the isolated DNA
      from the sample, and in control samples containing water instead of isolated DNA.
      This was followed by statistical analysis of the data. Inhibition and subsequent
      reduction of the endpoint fluorescence in the real-time PCR reaction was
      encountered in many cases. Less frequently, the target copy number in the samples
      was underestimated. However, we found no experimental evidence of a negative
      influence of the reduced endpoint fluorescence signal on the detection limit of
      the real-time PCR assay. All kits tested were useful for analyzing pelleted
      synovial fluid from horses, cattle and pigs. When analyzing non-pelleted synovial
      fluid, three kits - two based on silica columns and one employing a desalting
      process - yielded inhibitor-free DNA for real-time PCR analysis.

PMID- 17222993
TI  - Isolation of Leptospira noguchii from sheep.
AB  - The main goal of this study was to obtain new isolates of Leptospira spp. from
      sheep. A total of 10 kidney samples and 44 blood samples were collected from
      sheep slaughtered in Pelotas, Southern Brazil. One isolate was obtained which was
      identified by 16S rRNA gene sequencing and serogrouping to be Leptospira noguchii
      serogroup Autumnalis. Microscopic agglutination test (MAT) evaluation revealed
      that 4.5% of the sheep sera reacted against the Autumnalis serogroup. This is the
      first report of isolation of L. noguchii from sheep. Together these findings
      indicate that L. noguchii infections may be a potentially important veterinary
      problem in this domestic animal species.

PMID- 17222994
TI  - Differential gene expression of bone morphogenetic protein 15 and growth
      differentiation factor 9 during in vitro maturation of porcine oocytes and early
      embryos.
AB  - Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9)
      belong to the TGF-beta superfamily and are involved in the regulation of
      folliculogenesis. Though there are many reports concerning the expression and
      regulation of GDF9 in the process of oocyte maturation, expression of BMP15
      during oocyte maturation is still not clearly understood. It has been reported
      that BMP15 and GDF9 expression is important in folliculogeneiss and that the
      regulation of these two proteins is complex and species-specific. In this report,
      we investigated the expression of BMP15 and GDF9 genes during in vitro maturation
      (IVM) at 0, 6, 12, 18, 24, 30, 36, 42 and 48 h for porcine oocytes. Porcine GDF9
      gene was found to be highly expressed in immature oocytes and declined slowly
      during the oocyte maturation process. BMP15mRNA and its encoded protein were
      expressed at low levels in immature oocytes and increased to the highest level at
      18 h of IVM, which coincides with the time of cumulus cell expansion. Thus, these
      two genes were differentially expressed during the oocyte maturation process and
      BMP15 is specifically expressed during cumulus cell expansion in porcine oocytes.

PMID- 17222995
TI  - Does BAPTA leave outer hair cell transduction channels closed?
AB  - The calcium chelator BAPTA was iontophoresed into the scala media of the second
      turn of the guinea pig cochlea. This produced a reduction in low frequency
      cochlear microphonic (CM) measured in scala media and an elevation of the
      cochlear action potential (CAP) threshold that lasted for the duration of the
      experiment. Using two pipettes, one filled with KCl and the other KCl and BAPTA
      (50, 20 and 5 mM) it was possible to observe the effect of passing current
      through one electrode while measuring the endolymphatic potential (EP) with the
      other. The results demonstrated that current passed via the BAPTA pipette caused
      a sustained increase in EP of 8.2, 12.9 and 7.8 mV in the three animals used.
      This increase coincided with the decrease in low frequency CM that indicated a
      causal connection between the two. In a second series of experiments, pipettes
      with larger tips were inserted into scala media in the first cochlear turn and
      BAPTA was allowed to diffuse from the pipette. The results confirmed the
      relationship between EP increase and the fall of scala media CM. One
      interpretation of these results is that lowering the Ca2+ concentration of
      endolymph with BAPTA inhibits mechano-electrical transduction in outer hair cells
      (OHCs) and leaves the hair cell transduction channels in a closed state, thus
      increasing the resistance across OHCs and increasing the EP. These findings are
      consistent with a model of hair cell transduction in which tension on stereo
      cilia opens the transduction channels.

PMID- 17222996
TI  - Relaxation effects of ligustilide and senkyunolide A, two main constituents of
      Ligusticum chuanxiong, in rat isolated aorta.
AB  - Ligusticum chuanxiong Hort. (Umbelliferae) is a widely prescribed traditional
      Chinese medicinal herb for cardiovascular diseases in China. However, the
      cardiovascular actions of ligustilide and senkyunolide A, two of the most
      abundant Ligusticum chuanxiong constituents, have yet to be examined. The
      objective of the present study was to investigate the vasorelaxation effects of
      ligustilide and senkyunolide A and their underlying mechanisms in rat isolated
      aorta. Both constituents had similar relaxation potencies against contractions to
      9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F(2alpha), phenylephrine, 5
      hydroxytryptamine and KCl. Their vasorelaxation effects were not affected by
      endothelium removal, the adenylate cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H
      purin-6-amine, the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one, or the non-selective K+ channel blocker tetraethylammonium.
      This is the first report to demonstrate the vasorelaxation activities of
      ligustilide and senkyunolide A in contractions to various contractile agents in
      rat isolated aorta. The underlying mechanisms await further investigations.

PMID- 17222997
TI  - A comparison of pulmonary intra-alveolar hemorrhage in cases of sudden infant
      death due to SIDS in a safe sleep environment or to suffocation.
AB  - The differentiation of SIDS from accidental or inflicted suffocation may be
      impossible without corroborating findings from the death scene or autopsy or in
      the absence of a confession from a perpetrator. Pulmonary intra-alveolar
      hemorrhage (PH) has been proposed as a potential clue to suffocation, but none of
      the previous studies on this topic have limited SIDS cases to those who were in a
      safe sleep environment, in which all were found supine and alone on a firm
      surface with their heads uncovered. Our aims are to: (1) compare PH in SIDS cases
      found in a safe sleep environment to a control group comprised of infants whose
      deaths were attributed to accidental or inflicted suffocation and (2) assess the
      effect of age, CPR, and postmortem interval (PMI), with regard to the severity of
      PH in this subset of safe-sleeping SIDS cases. We conducted a retrospective study
      of all postneonatal cases accessioned by the Office of the Medical Examiner in
      San Diego County, California who died of SIDS or suffocation between 1999 and
      2004. A total of 74 cases of sudden infant death caused by SIDS (34 cases as
      defined above, comprising 8% of the total SIDS cases), accidental suffocation
      (37), and inflicted suffocation (3) from the San Diego SIDS/SUDC Research Project
      database were compared using a semiquantitative measure of pulmonary intra
      alveolar hemorrhage. The most severe (grade 3 or 4) PH occurred in 35% of deaths
      attributed to suffocation, but in only 9% of the SIDS cases. Age, duration of CPR
      attempts and PMI had no effect on the severity of PH in SIDS. Our results
      indicate that the severity of PH cannot be used independently to differentiate
      SIDS from suffocation deaths. Each case must be evaluated on its own merits after
      thorough review of the medical history, circumstances of death, and postmortem
      findings.

PMID- 17222998
TI  - The routine use of C-reactive protein in forensic investigations.
AB  - In clinical medicine, C-reactive protein (CRP) is extensively used as a general
      marker for immune system activation, and post-mortem applicability has been
      established [M.Q. Fujita, B.L. Zhu, K. Ishida, L. Quan, S. Oritani, H. Maeda,
      Serum C-reactive protein levels in postmortem blood-an analysis with special
      reference to the cause of death and survival time, Forensic Sci. Int. 130 (2002)
      160-166; L. Uhlin-Hansen, C-reactive protein (CRP), a comparison of pre- and post
      mortem blood levels, Forensic Sci. Int. 124 (2001) 32-35]. We have analysed the
      routine use of CRP in non-selected cases. Scarcity of blood available for
      analysis is a common problem in forensic investigation, and in response to this
      we have developed a method using liver as a source. In 50 consecutive autopsy
      cases, we have evaluated method, validated results and discussed their
      interpretation. In three cases the analysis was not possible. For each of the
      remaining cases (n=47) we have analysed whole blood, serum and/or liver samples.
      57% (n=25) had serum CRP > 10 mg/L. Serum levels were higher than in whole blood
      or liver. CRP levels in serum and whole blood samples were stable in more than
      one month after death, making storage for later analysis possible. Liver levels
      peaked at one week, but after one month putrefaction was obvious. CRP levels were
      independent of the post-mortem interval. The use of liver as a source has not yet
      been described in literature. Our results in liver samples correlate well with
      plasma results, and liver is a good post-mortem alternative when blood is not
      available. We conclude that CRP measurements are easy, viable and inexpensive in
      a forensic setting, and that the number of cases with CRP elevation is high in a
      non-selected forensic material. In cases of doubt, marked elevation of CRP is an
      indicator of natural mode of death, and in cases of trauma, it indicates vital
      reaction. It can be used as a pre-autopsy screening, leading to a more extensive
      search for diseases not easily diagnosed, such as sepsis or ketoacidosis.

PMID- 17222999
TI  - Medicolegal assessment of blood transfusion errors--an interdisciplinary
      challenge.
AB  - Given a current total incidence of erroneously administered blood transfusions of
      1:12,000-1:36,000 (AB0 incompatible 1:38,000), the percentage of lethal outcomes
      ranges between 2 and 5%; i.e. the sole fact of an erroneous transfusion does not
      mandatorily result in a causal connection with lethal outcome, which can give
      rise to problems in the medicolegal assessment. We report on the conception and
      results of a novel interdisciplinary approach to assess the lethal significance
      of blood transfusion errors. Besides autopsy, histological investigation and
      immunohistochemical detection of AB0 incompatible foreign red blood cells in
      autopsy specimens, transfusion medicine investigations offer the opportunity to
      assess several immunohaematologic features. We assessed the immunohaematologic
      gel card ("microcolumn") technique for suitability in the forensic assessment of
      an AB0 incompatible transfusion incident in a septic patient, who had had no
      history of previous blood transfusions, with lethal outcome. After such an
      erroneous transfusion had been simulated in vitro, pre-transfusion and cadaver
      patient blood samples (p.m. interval: 3 days) were analysed. Amongst other
      things, IgG-loaded erythrocytes were detected in pre- and post-transfusion
      samples; the presence of irregular antibodies directed against blood group
      antigens and anti-A or anti-B isoagglutinins, respectively, especially in the pre
      transfusion sample was ruled out. Besides the demonstration of AB0 incompatible
      red blood cells in the cadaver blood sample, blood group incompatibilities other
      than AB0 were excluded. With regard to the cause of death, in synopsis with
      autopsy findings and clinical symptoms, the results did not allow for a final
      discrimination between the impact of the pre-existing septic inflammatory
      response syndrome and sepsis, respectively, and potential lethal effects of a
      (haemolytic) transfusion reaction. Besides pre- and post-transfusion
      compatibility testing in clinical transfusion medicine as required by German
      National Guidelines, the reported immunohaematologic investigations offer an
      important supportive tool for the forensic assessment of lethal erroneous
      transfusions and investigation of blood samples of survivors of transfusion
      incidents as well. Besides established morphological techniques, they allow for a
      certain evaluation of the pathophysiological impact of transfusion incidents as
      well as a diversified assessment of immunohaematologic features beyond the AB0
      system.

PMID- 17223000
TI  - The inhibitory effect of the leukotriene receptor antagonist on leukotriene D4
      induced MUC2/5AC gene expression and mucin secretion in human airway epithelial
      cells.
AB  - OBJECTIVES: Mucin gene expression and mucin production are markedly increased in
      inflammatory airway disorders such as asthma, chronic bronchitis and
      rhinosinusitis. Cytokines, lipopolysaccharides and other inflammatory mediators
      such as prostaglandin and leukotriene are related to the secretion and production
      of mucin. However, the relationship of leukotrienes with mucin genes expression
      is not clear. The aim of this study is to evaluate MUC2/5AC gene expression and
      mucin secretion by the leukotriene receptor in human airway epithelial cells.
      METHODS: The effect of leukotriene D(4) and the leukotriene receptor antagonist,
      pranlukast hydrate (ONO-1078) on the regulation of MUC2/5AC gene expression and
      mucin secretion were observed in human airway NCI-H292 epithelial cells. The mRNA
      levels of MUC2/5AC and the amount of mucin were determined by reverse
      transcription-polymerase chain reaction (RT-PCR) and immunoassay. RESULTS:
      Leukotriene D(4) upregulated MUC2/5AC gene expression and mucin secretion in a
      dose dependent pattern. Pranlukast hydrate (ONO-1078, 100 microM) downregulated
      the leukotriene D(4)-induced MUC2/5AC gene expression and mucin secretion.
      CONCLUSION: These results suggest that the leukotriene receptor system is one of
      the mechanisms related to MUC2/5AC gene expression and mucin secretion in the
      human airway epithelium.

PMID- 17223001
TI  - Histopathologic study of minced and injected expanded polytetrafluoroethylene
      (Gore-Tex) in quadriceps muscle of rats for injection laryngoplasty.
AB  - OBJECTIVE: Gore-Tex has not yet been used as an injection material, and no animal
      study has been performed. The purpose of this study was to investigate the
      histopathological and volumetric changes of minced and injected expanded
      polytetrafluoroethylene (Gore-Tex) in the quadriceps muscle of rats to find out
      its possibility as an injection material in future injection laryngoplasty.
      DESIGN: A prospective study was performed in 13 Wistar rats. METHODS: The 50+/-5
      mg Gore-Tex vascular graft was minced until it was fine enough to pass through a
      16G injection cannula. To create viscosity in order to avoid precipitation,
      minced Gore-Tex was mixed with sodium hyaluronate (SH) gel. 0.5 ml of this
      mixture was injected into the middle part of the right quadriceps muscle of each
      subject. Then, pure SH (0.5 ml) was injected into the middle part of the left
      quadriceps muscle of each subject. To compare the volumetric and
      histopathological changes of the injection area occupied by the materials over
      the time, two rats were sacrificed 1 day after the procedure, four rats after 1
      month, four rats after 3 months and three rats after 6 months. RESULTS: In pure
      SH: SH was observed as an effusion in the muscle of one subject on the first day
      only. We did not detect SH in the muscle in the first, third and sixth months
      and, as a result, there was no augmentation. Inflammation and fibrosis was not
      detected in any of these applications of SH. In minced Gore-Tex+SH gel mixture:
      SH was again eliminated from the muscle in a very short period of time, but the
      remaining Gore-Tex created a 15.8% volumetric gain. Fibrosis and capsule
      formation began in the first month and, in the sixth month; we observed
      connective tissue surrounding the Gore-Tex material. Ingrowth of connective
      tissue into the Gore-Tex, though not present in the first month, occurred
      partially in the third and significantly in the sixth month. In addition, we
      observed foreign body granuloma formation after the third month. CONCLUSIONS:
      Pure SH, though easily applicable, was immediately eliminated leaving no trace.
      In the relatively difficult applications of Gore-Tex mixed with SH, however,
      there was residual Gore-Tex present in all subjects throughout the study. Gore
      Tex may be an applicable material for injection laryngoplasty.

PMID- 17223002
TI  - MR mammography is useful in the preoperative locoregional staging of breast
      carcinomas with extensive intraductal component.
AB  - PURPOSE: To determine the role of magnetic resonance (MR) mammography in
      detection and assessment of extent of tumors with extensive intraductal component
      (EIC+). MATERIAL AND METHODS: In a prospective study, 233 consecutive women with
      a suspicious lesion underwent preoperative MR mammography and 209 invasive ductal
      carcinomas were detected. We studied the prediction of intraductal spread on
      mammography (MX), ultrasound (US) and MR. We compared the size of the total
      lesion on MX, US and MR and correlated it with histopathology. Enhancement
      patterns on MR were described. RESULTS: Of 209 invasive ductal carcinomas, 50
      were EIC+ (24%). MX predicted intraductal spread in EIC+ carcinomas in 48.5%, US
      in 34.2% and MR in 68%. Compared to MX and US, MR was best in assessment of total
      tumor size. On MR, ductal spread in EIC+ tumors presented as ductal or linear
      enhancement, long spicules, a regional enhancing area or nodules adjacent to a
      mass. CONCLUSION: MR had the highest sensitivity to predict intraductal spread
      and was superior in assessing total tumor size.

PMID- 17223003
TI  - Evaluation of suspected local recurrence in head and neck cancer: a comparison
      between PET and PET/CT for biopsy proven lesions.
AB  - BACKGROUND: (18)F-FDG PET has a high accuracy for re-staging of head and neck
      cancer. The purpose of this study was to determine whether the diagnostic
      accuracy can be further improved with integrated PET/CT. MATERIALS AND METHODS:
      Forty-nine patients with a mean age of 59+/-18 years were studied
      retrospectively. Histo-pathological verification was available either from
      complete tumor resection with or without lymph node dissection (n=27) or direct
      endoscopic biopsy (n=16) or ultrasound guided biopsy (n=6). Two reviewers blinded
      to the pathological findings read all PET images in consensus. An experienced
      radiologist was added for the interpretation of the PET/CT images. RESULTS:
      Tissue verification was available for 110 lesions in 49 patients. Sixty-seven
      lesions (61%) were biopsy positive and 43 (39%) were negative for malignant
      disease. PET and PET/CT showed an overall accuracy for cancer detection of 84 and
      88% (p=0.06), respectively. Sensitivity and specificity for PET were 78 and 93%
      versus 84 (p=NS) and 95% (p=NS) with PET/CT. A patient-by-patient analysis
      yielded a sensitivity, specificity and accuracy for PET of 80, 56 and 76%,
      compared to 88% (p=NS), 78% (p=NS) and 86% (p=0.06) for PET/CT. CONCLUSION: The
      results of this study indicate that PET/CT does not significantly improve the
      detection of recurrence of head and neck cancer. However, a trend towards
      improved accuracy was observed (p=0.06).

PMID- 17223004
TI  - Preoperative or postoperative self-efficacy: which is a better predictor of
      outcome after total hip or knee arthroplasty?
AB  - OBJECTIVE: Self-efficacy is considered an important determinant of outcome after
      total hip or knee arthroplasty. Aim of this study is to evaluate the
      contributions of preoperative and short-term postoperative self-efficacy in
      predicting long-term outcome. METHODS: Self-efficacy was determined in 103 total
      hip and knee arthroplasty patients preoperatively and 6 weeks postoperatively
      with the Self-Efficacy for Rehabilitation Outcome Scale (SER). The 6-month
      outcome was assessed with a disease-specific and a generic self-report
      questionnaire and an objective measure of function (walking speed). Multiple
      linear regression analyses were used to examine the value of preoperative and
      short-term postoperative self-efficacy in predicting 6-month outcomes. RESULTS:
      Preoperative self-efficacy was only a significant predictor of long-term
      postoperative walking speed, with higher self-efficacy resulting in faster
      walking speed at the long-term measurement (R(2)=0.47). Short-term postoperative
      self-efficacy was a significant predictor of the long-term postoperative generic
      outcome measure (physical functioning: R(2)=0.30; mental health: R(2)=0.53) and
      of walking speed (R(2)=0.66), with higher self-efficacy resulting in a better
      long-term outcome. CONCLUSION: Short-term postoperative self-efficacy seems a
      better predictor of long-term outcome after total hip or knee arthroplasty than
      preoperative self-efficacy. PRACTICE IMPLICATIONS: Interventions should focus on
      enhancing short-term postoperative rather than preoperative self-efficacy.

PMID- 17223005
TI  - Postprandial blood hormone and metabolite concentrations influenced by feeding
      frequency and feeding level in veal calves.
AB  - This study hypothesized that increased feeding frequency (FF) decreases problems
      with glucose homeostasis seen at high feeding levels (FL) in heavy veal calves.
      Effects of FF and FL on hormone and metabolite concentrations were studied in 15
      heavy veal calves fed once (FF1; at 12:00), twice (FF2; at 12:00 and 24:00) or
      four times daily (FF4; at 06:00, 12:00, 18:00 and 24:00). In period 1, all calves
      were fed at a low FL (FL(low); 1.5 x metabolizable energy requirements for
      maintenance, ME(m)). In period 2, FF2 and FF4 calves were fed at high FL
      (FL(high); 2.5 x ME(m)), whereas FF1 calves were still fed at FL(low). Blood was
      sampled every 30 min from 12:00 to 18:00 and postprandial integrated plasma
      hormone and metabolite concentrations (AUC(12-18 h)) were calculated. Glucose
      AUC(12-18 h) increased with increasing FL, but decreased with increasing FF, urea
      AUC(12-18 h) increased with increasing FL, whereas non-esterified fatty acid
      AUC(12-18 h) were unaffected by FL and FF. Insulin AUC(12-18 h) decreased with
      increasing FF and decreasing FL. Glucagon AUC(12-18 h) increased with increasing
      FL and FF. Growth hormone AUC(12-18 h) decreased, whereas insulin-like growth
      factor-1 and leptin AUC(12-18 h) increased with increasing FL. Mean thyroxine and
      3,5,3'-triiodothyronine concentrations were modified by FF and FL. There were no
      FF x FL interactions, except for plasma glucose. In conclusion, postprandial
      hormone and metabolite responses were differentially affected by FF and (or) FL.
      Glucose and insulin concentrations were maximally increased at high FL and low
      FF. Hyperglycemia, glucosuria and excessive insulinemia were prevented by
      increasing FF and decreasing FL.

PMID- 17223006
TI  - Ovine endometrial expression of fibroblast growth factor (FGF) 2 and conceptus
      expression of FGF receptors during early pregnancy.
AB  - In ruminants, conceptus development beyond the blastocyst state requires input
      from uterine-derived factors. Fibroblast growth factor 2 (FGF2) is expressed by
      the bovine endometrium throughout the estrus cycle and early pregnancy and
      stimulates trophectoderm expression of interferon-tau, the maternal recognition
      of pregnancy factor in ruminants. The objective of this study was to examine the
      expression of FGF2 in ovine endometrium and peri-attachment conceptuses and FGF
      receptors (FGFR) in conceptuses. FGF2 mRNA was present in the ovine endometrium
      with specific localization within the luminal and glandular epithelium. No
      pregnancy-dependent changes in endometrial FGF2 mRNA abundance were detected
      until placental attachment was well underway. FGF2 protein was detected in the
      uterine lumen throughout the estrous cycle and early pregnancy. Concentrations of
      luminal FGF2 protein did not differ based on pregnancy status. However, uterine
      luminal FGF2 protein levels increased at days 12-13 after estrus in both cyclic
      and pregnant ewes. Ovine conceptuses collected at days 14-19 after mating
      contained transcripts for FGF2 and FGFR types 1, 2 and 3. In summary, FGF2 is
      expressed by the ovine endometrium and conceptus during early pregnancy, and peri
      attachment conceptuses possess several FGFR types. Concentrations of FGF2 protein
      in the uterine lumen increase coincident with the initiation of pregnancy
      recognition in ewes. These observations support the concept that FGF2 and
      potentially other FGFs may affect conceptus development and/or gene expression
      during early pregnancy in ruminants.

PMID- 17223007
TI  - Polymorphic analysis of the matrix metalloproteinase-9 gene and susceptibility to
      sporadic abdominal aortic aneurysm.
AB  - Abdominal aortic aneurysm (AAA) has a multifactorial aetiology and the importance
      of genetic components is getting increasing interest. Alteration in the structure
      of the vascular extracellular matrix has been described in AAA. Matrix
      metalloproteinases (MMPs) degrade extracellular matrix proteins which alter the
      vessel wall stability. We evaluated two different polymorphisms, a CA repeat and
      a cytosine to thymidine transition in the promoter sequence of MMP-9 gene for
      frequency in 146 patients with AAA. We compared the results with those of 156
      healthy subjects. No difference was found in the allelic distribution of either
      polymorphisms. We therefore found no evidence that MMP-9 is a marker of
      susceptibility for AAA.

PMID- 17223008
TI  - OPC-28326, a selective femoral arterial vasodilator, augments ischemia induced
      angiogenesis.
AB  - OPC-28326, 4-(N-methyl-2-phenylethylamino)-1-(3,5-dimethyl-4-propionyl
      aminobenzoyl) piperidine hydrochloride monohydrate, is a newly developed
      selective peripheral vasodilator and increases blood flow to lower extremities
      with alpha2-adrenergic antagonist property. Here, we investigated the effect of
      OPC-28326 on ischemia-induced angiogenesis. OPC-28326 enhanced tube formation by
      human aortic endothelial cells (HAECs). Moreover, OPC-28326 enhanced the number
      of microvessels sprouting from aortic rings embedded in collagen gel. OPC-28326
      markedly induced phosphorylation of endothelial nitric oxide synthase (eNOS) in
      HAECs via phosphatidylinositol-3 kinase PI3K/Akt (PI3K/Akt) pathway. Next, the
      angiogenic effect of OPC-28326 was evaluated in a mouse hindlimb ischemia model.
      Blood flow recovery to the ischemic leg was significantly enhanced by OPC-28326.
      Furthermore, anti-CD31 immunostaining revealed that OPC-28326 increased capillary
      density in the ischemic muscle. However, OPC-28326 failed to promote blood flow
      recovery in ischemic hindlimb in eNOS-deficient mice. These results suggest that
      OPC-28326 promotes angiogenesis, which was associated with activation of eNOS via
      PI3K/Akt pathway. OPC-28326 might be promising to treat patients with ischemic
      vascular diseases.

PMID- 17223009
TI  - Endogenous retroviral insertion in Cryge in the mouse No3 cataract mutant.
AB  - No3 (nuclear opacity 3) is a novel congenital nuclear cataract in mice.
      Microsatellite mapping placed the No3 locus on chromosome 1 between D1Mit480
      (32cM) and D1Mit7 (41cM), a region containing seven crystallin genes; Cryba2 and
      the Cryga-Crygf cluster. Although polymorphic variants were observed, no
      candidate mutations were found for six of the genes. However, DNA walking
      identified a murine endogenous retrovirus (IAPLTR1: ERVK) insertion in exon 3 of
      Cryge, disrupting the coding sequence for gammaE-crystallin. Recombinant protein
      for the mutant gammaE was completely insoluble. The No3 cataract is mild compared
      with the effects of similar mutations of gammaE. Quantitative RT-PCR showed that
      gammaE/F mRNA levels are reduced in No3, suggesting that the relatively mild
      phenotype results from suppression of gammaE levels due to ERVK insertion.
      However, the severity of cataract is also strain dependent suggesting that
      genetic background modifiers also play a role in the development of opacity.

PMID- 17223010
TI  - A two-generation reproductive toxicity study of octamethylcyclotetrasiloxane (D4)
      in rats exposed by whole-body vapor inhalation.
AB  - This study evaluated the potential toxicity of whole-body vapor inhalation of
      octamethylcyclotetrasiloxane (D(4)) on reproductive capabilities in exposed F(0)
      and F(1) parental animals and the potential effects on neonatal survival, growth,
      and development of the F(1) and F(2) offspring. F(0) male and female Sprague
      Dawley rats (30/sex/group) were exposed to D(4) vapor at concentrations of 0, 70,
      300, 500 or 700 ppm 6h per day for at least 70 consecutive days prior to mating
      and lasted through weaning of the pups on postnatal day (PND) 21. Female
      exposures were suspended from gestation day (GD) 21 through PND 4 to allow for
      parturition and permit continuous maternal care for the early neonates. Starting
      on PND 22, F(1) weanlings were exposed to D(4) as described for the F(0)
      generation. The F(2) pups were not directly exposed to D(4). F(0) animals were
      mated once to produce the F(1) generation; F(1) parental animals were mated twice
      to produce two F(2) litters. In addition, the F(1) males were mated with
      unexposed females. Prolonged estrous cycles, decreased mating and fertility
      indices were observed in the F(1) generation exposed to D(4) for the first and
      second matings. Significant reductions in the mean number of pups born and mean
      live litter size were observed in the 500 and 700 ppm groups for both the F(0)
      and F(1) generations. Implantation sites were also reduced at 700 ppm for both
      F(0) and F(1) generations. No adverse effects were observed at any exposure level
      on anogenital distance, vaginal patency and preputial separation. No adverse
      effects were seen on male functional reproductive parameters, spermatogenic
      endpoints, microscopic evaluation of male reproductive tissue, or when the D(4)
      exposed F(1) males were mated with the unexposed females, demonstrating that the
      reproductive toxicity observed was due to D(4) exposure to the females. Based on
      the lack of effect on reproduction when the D(4)-exposed males were mated to
      naive females, the NOAEL for male reproductive toxicity was considered to be 700
      ppm. Based on the statistically significant effects on fertility and litter size,
      NOAEL for female reproductive toxicity was considered to be 300 ppm. The findings
      observed in this study are consistent with suppression or delaying of LH surge as
      well as acceleration of the onset of female reproductive senescence in the rat.
      While analogous pathways control ovulation in both rats and humans, there are
      significant differences in the mechanism for timing and release of LH and
      resulting changes in the control of ovulation and mating behavior between the two
      species. If D(4) delays rather than causes a prolonged suppression or ablation of
      the LH surge, the reproductive mode of action of D(4) would not likely be
      relevant for humans.

PMID- 17223011
TI  - Constant illumination causes spatially discrete dopamine depletion in the normal
      and degenerate retina.
AB  - A fully competent retinal dopamine system underpins normal visual function.
      Although this system is known to be compromised both prior to and during retinal
      degeneration, the spatial dynamics of dopamine turnover within the degenerate
      retina are at present unknown. Here, using immunohistochemistry for dopamine in
      combination with quantitative optical density measurements, we reveal a global
      decline in retinal dopamine levels in the light adapted RCS dystrophic rat, which
      is restricted to plexiform layers in the dark. Pharmacological blockade of
      dopamine production with the drug alpha-methyl-p-tyrosine (AMPT) allows the
      direct visualisation of dopamine depletion in normal and degenerate retina in
      response to constant illumination. In normal retinae this effect is spatially
      discrete, being undetectable in perikarya and specific to amacrine cell fibres in
      sublamina 1 of the inner plexiform layer. A similar response was observed in the
      retinae of dystrophic rats but with a reduction in amplitude of approximately
      50%. It is suggested that the pattern of dopamine depletion observed in rat
      retina may reflect an AMPT-resistant pool of perikaryal dopamine and/or a
      reduction in extrasynaptic release of this neurotransmitter in response to
      illumination in vivo. We conclude that the visualisation of dopamine depletion
      reported here represents a release of this neurotransmitter in the response to
      light. Turnover of dopamine in the dystrophic retina is discussed in the context
      of surviving photoreceptors, including the intrinsically photosensitive
      melanopsin ganglion cells of the inner retina.

PMID- 17223012
TI  - Growth and differentiation of mouse osteoblasts on chitosan-collagen sponges.
AB  - The aim of this study was to investigate the effects of collagen on the
      microstructure and biocompatibility of chitosan-collagen composite sponges
      fabricated by a freezing and drying technique. The study was categorized into
      four groups: Group I: collagen; Group II: chitosan; Group III: 1:1 (by wt)
      chitosan-collagen and Group IV: 1:2 (by wt) chitosan-collagen sponges. A mouse
      osteoblast cell line, MC3T3-E1, was cultivated on the sponges in a mineralized
      culture medium for 21 days. Microstructure of scaffolds and growth of cells on
      the sponges were examined using scanning electron and confocal laser scanning
      electron microscopes. Pore size was analysed from scanning electron microscope
      images using Image-Pro Plus image analysis software. Cell viability (MTT assay),
      alkaline phosphatase activity and levels of osteocalcin and calcium were
      monitored every 3 days and on days 15 and 21, respectively. It was found that the
      sponges were porous with average pore sizes of 80-100 microm. A combination of
      chitosan and collagen matrixes created a well defined porous microstructure and
      biocompatible scaffolds. Chitosan-collagen composite sponges promoted growth and
      differentiation of osteoblasts into the mature stage. To optimize application of
      the composite sponges in bone regeneration, the fabrication process must be
      improved to increase the pore size of the scaffolds.

PMID- 17223014
TI  - A French CDK4-positive melanoma family with a co-inherited EDNRB mutation.

PMID- 17223013
TI  - Expression of transcripts for myelination-related genes in the anterior cingulate
      cortex in schizophrenia.
AB  - Several recent studies have found changes in the expression of genes functionally
      related to myelination and oligodendrocyte homeostasis in schizophrenia. These
      studies utilized microarrays and quantitative PCR (QPCR), methodologies which do
      not permit direct, unamplified examination of mRNA expression. In addition, these
      studies generally only examined transcript expression in homogenates of gray
      matter. In the present study, we examined the expression of myelination-related
      genes previously implicated in schizophrenia by microarray or QPCR. Using in situ
      hybridization, we measured transcript expression of 2',3'-cyclic nucleotide 3'
      phosphodiesterase (CNP), myelin-associated glycoprotein (MAG), transferrin (TF),
      quaking (QKI), gelsolin, myelin oligodendrocyte glycoprotein, v-erb-b2
      erythroblastic leukemia viral oncogene homolog 3, erbb2 interacting protein,
      motility-related protein-1, SRY-box containing gene 10, oligodendrocyte
      transcription factor 2, peripheral myelin protein 22, and claudin-11 in both gray
      and white matter of the anterior cingulate cortex (ACC) in subjects with
      schizophrenia (n=41) and a comparison group (n=34). We found decreased expression
      of MAG, QKI, TF, and CNP transcripts in white matter. We did not find any
      differences in expression of these transcripts between medicated (n=31) and
      unmedicated (n=10) schizophrenics, suggesting that these changes are not
      secondary to treatment with antipsychotics. Finally, we found significant
      positive correlations between QKI and MAG or CNP mRNA expression, suggesting that
      the transcription factor QKI regulates MAG and CNP expression. Our results
      support the hypothesis that myelination and oligodendrocyte function are impaired
      in schizophrenia.

PMID- 17223015
TI  - B cell signaling and autoimmune diseases: CD19/CD22 loop as a B cell signaling
      device to regulate the balance of autoimmunity.
AB  - Autoimmune diseases, including connective tissue diseases and bullous diseases,
      may be life-threatening. Recent clinical and experimental approaches have
      demonstrated that B cells play critical roles in the manifestation of autoimmune
      disease not only by well-established autoantibody-mediated mechanisms but also by
      a variety of other functions. These B cell functions are under the regulation of
      B cell antigen receptor (BCR)-induced signals and by specialized cell surface
      coreceptors, or "response regulators", which inform B cells of their
      microenvironment. These response regulators include CD19 and CD22. CD19 and CD22
      do not merely regulate BCR signals independently, but they have their own
      regulatory network. CD19 regulates CD22 phosphorylation by augmenting Lyn kinase
      activity, while CD22 inhibits CD19 phosphorylation via SHP-1. Importantly, this
      "CD19/CD22 loop" is significantly related to an autoimmune phenotype in mice.
      Thus, the CD19/CD22 loop may be a potential therapeutic target in autoimmune
      disease for modulating B cell signaling.

PMID- 17223016
TI  - Comparative in vitro killing of carbapenems and aztreonam against Klebsiella
      pneumoniae producing VIM-1 metallo-beta-lactamase.

PMID- 17223017
TI  - Elevation of rat plasma P-selectin in acute lung injury.
AB  - Acute lung injury in the rat caused by intravenous (i.v.) infusion of cobra venom
      factor (CVF) or lipopolysaccharide (LPS) is mediated by P-selectin-dependent
      neutrophil infiltration into the lung. In these lung injury models, P-selectin
      expression is induced on lung vascular endothelial cells after the CVF or LPS
      infusion, suggesting soluble P-selectin derived from inflamed sites might also be
      elevated. Here we established a sensitive enzyme-linked immunosorbent assay
      (ELISA) to measure soluble P-selectin in plasma, a potential marker of lung
      injury. Nine anti-rat P-selectin monoclonal antibodies that we established
      previously were first classified into 5 groups based on real-time biospecific
      interaction analyses, and used to develop a sandwich ELISA for accurately
      measuring the amount of soluble P-selectin in plasma. We then used this ELISA to
      measure the plasma P-selectin levels in Long Evans, Wistar, and Sprague-Dawley
      rats after the i.v. infusion of CVF or LPS. The elevation in P-selectin levels
      was significantly different among the strains, but it consistently correlated
      with the extent of lung inflammation, measured by myeloperoxidase levels in the
      lung tissues. Thus, our results indicate that the soluble P-selectin in plasma
      could serve as a sensitive biomarker reflecting lung inflammation, which is of
      clinical importance for detecting and preventing severe lung injury.

PMID- 17223018
TI  - Molecular cloning and expression analysis of a RanBP2 zinc finger protein gene in
      upland cotton (Gossypium hirsutum L.).
AB  - Gossypol is an important resistant substance of Gossypium, and its storage organ
      is pigment gland. Although, the relationship between gossypol and pigment gland
      has been studied for a long time, the development mechanism of pigment gland has
      not been revealed up to now in molecular perspective. On the basis of
      differentially expressed cDNAs fragments at the stage of the cotton gland
      development using suppression subtractive hybridization (SSH), the complete cDNA
      sequence of a novel RanBP2 zinc finger protein (ZFP) gene was cloned by rapid
      amplification of cDNA ends (RACE) from upland cotton (Gossypium hirsutum L.),
      Xiangmian 18. The cotton RanBP2 ZFP cDNA (GenBank accession number: DQ173926) is
      717 base pair (bp) long with an open reading frame encoding 139 amino acids,
      which encodes a 15.6 kDa protein. The cotton RanBP2 ZFP had three Ran-binding
      protein (RanBP) two zinc finger motifs and belonged to RanBP2 ZFP family. There
      is a 292-base non-coding sequence at 3' cDNA end, which includes polyA sequence.
      Sequence alignment analysis revealed that the cDNA nucleotide and its deduced
      amino acid sequence are moderately identical to the putative ZFP from other
      species. The mRNA expressing profiles of the novel ZFP gene was investigated by
      reverse transcription-polymerase chain reaction (RT-PCR). The result showed that
      it expressed at different development stages of gland, including the undeveloped
      stage, developing stage, developed stage and cotyledon stage. However, with the
      development of pigment gland, the mRNA levels in the gland-developed seed and
      cotyledon were increased to about 1.5 and 2 folds of that in gland-undeveloped
      seed, respectively, which suggested that the novel ZFP played a role in the
      development of the cotton gland.

PMID- 17223019
TI  - Polymeric micelle systems of hydroxycamptothecin based on amphiphilic N-alkyl-N
      trimethyl chitosan derivatives.
AB  - This research investigated the possible utilization of amphiphilic N-octyl-N
      trimethyl chitosan (OTMCS) derivatives in solublization and controlled release of
      10-hydroxycamptothecin (10-HCPT), a hydrophobic anticancer drug. The release
      behavior of the 10-HCPT-OTMCS micelles was measured and compared to that of a
      commercial 10-HCPT lyophilized powder in vitro and in vivo. This research also
      examined the effects of chemical structure of the chitosan derivatives and the
      micellar preparation conditions on the encapsulation efficiency, drug loading
      content, and particle size of the polymeric micelles. The results showed that
      these chitosan derivatives were able to self-assemble and form spherical shape
      polymeric micelles with an average particle size range of 24-280 nm and a drug
      loading content of 4.1-32.5%, depending on the modified structures and loading
      procedures. The solubility of 10-HCPT in aqueous fluid was increased about 80,000
      fold from 2 ng/ml in water to 1.9 mg/ml in OTMCS micellar (degree of octyl and
      trimethyl substitution is 8% and 54%, respectively) solution. In addition, OTMCS
      was able to modulate the in vitro release of 10-HCPT and improve its
      pharmacokinetic properties and lactone ring stability in vivo. These data
      suggested the possible utilization of the amphiphilic micellar chitosan
      derivatives as carriers for hydrophobic drugs for improving their delivery and
      release properties.

PMID- 17223020
TI  - Liposomal drugs dispersed in hydrogels. Effect of liposome, drug and gel
      properties on drug release kinetics.
AB  - Release of calcein and griseofulvin (GRF) from control (gels in which solutes are
      dissolved in) and liposomal gels was studied using agarose-assisted
      immobilization as a technique to separate gels from drug-receptor compartments.
      Liposomes composed of phosphatidylcholine (PC) or distearoyl-glycero-PC and
      cholesterol (DSPC/Chol), and incorporating calcein or GRF were prepared by thin
      film hydration. After cleaning the liposomes they were dispersed in different
      hydrogels (carbopol 974 [1, 1.5 or 2% (w/w)], hydroxylethyl-cellulose (HEC) [4%
      (w/w)], or a mixture of the two), and release of calcein or GRF was followed by
      fluorescence or photometric technique, respectively. Results show that calcein
      release from liposomal gels is slower compared to control gels, and can be
      further retarded by using rigid-membrane liposomes (faster release from PC
      liposome compared to DSPC/Chol-liposome gels). Additionally, calcein release is
      not affected by the lipid amount loaded (in the range from 2 to 8 mg/ml),
      therefore solute loading can be controlled according to needs. Oppositely, GRF
      release from liposomal gels is determined by drug loading. At high drug loading
      levels (compared to GRF aqueous solubility), GRF is released with constant rate
      from liposomal gels irrespective of liposome type (PC or DSPC/Chol). Thereby, for
      amphiphilic/lipophilic drugs, drug properties (solubility, log P) determine the
      system behavior. Calcein and GRF release from control carbopol gels is faster
      compared to HEC and mixture gels. The same is true for calcein in liposomal gels.
      Carbopol gel rheological properties were found to be significantly different
      (compared to the other gels), implying that these characteristics are important
      for drug diffusion from gels.

PMID- 17223021
TI  - The preparation of pellets containing a surfactant or a mixture of mono- and di
      gylcerides by extrusion/spheronization.
AB  - The ability to incorporate either of the two components of a self-emulsifying
      system (polysorbate 80 (PSG80) and a mixture of mono- and di-glycerides (MDG))
      separately into pellets prepared by extrusion/spheronization and the properties
      of any resulting pellets has been investigated. The results have established that
      it is possible to prepare satisfactory pellets thus adding to the range of
      ingredients that can be included in pellet formulations. For PS80, it was found
      possible to prepare pellets containing at least 92% of the surfactant/water
      mixture, but with a mixture of (MDG) and water, however, it was not possible to
      prepare pellets, which contained more than 46% of MDG. By analysis of variance
      significant relationships were established between the ratio of lactose to MCC
      and the ratio of the PS80 or MDG to water and the properties of the pellets.
      There were both similarities and differences of the two input factors, which
      provided relationships for the two materials. The quantity of liquid required,
      the fluid content of the pellets, the tensile strength and porosity of the
      pellets provided relationships for both systems, whereas the extrusion force and
      the median pellet size gave relationships for the PS80 systems, but they did not
      for the MDG systems. The opposite was true for interquartile range (IQR), the
      yield in the modal fraction and the shape factor. It was possible to identify
      global relationships for these systems and those reported previously, when the
      two components were combined as a self-emulsifying system, by the application of
      perceptual mapping. It was found that, there were relationships between the size
      range, expressed as the IQR and the fluid level required to make pellets; the
      quantity of the non-aqueous component of the fluid and the pellet shape factor;
      the extrusion force and the tensile strength of the pellets and the yield in the
      modal fraction and the ratio of the non-aqueous to aqueous content of the fluid
      used to prepare the pellets. The ability to use the materials independently
      offers further alternatives for the formulation of water insoluble drugs into
      pellet formulations.

PMID- 17223022
TI  - Distribution and clearance of bioadhesive formulations from the olfactory region
      in man: effect of polymer type and nasal delivery device.
AB  - There is an increasing need to identify novel approaches by which to improve the
      efficiency of drug transport from the nasal cavity (olfactory region) to the CNS,
      especially for treatment of central nervous system disorders. It is suggested,
      that one approach is the combination of active targeting of a bioadhesive
      formulation, that will retain the drug at the absorption site, potentially in
      combination with, an absorption enhancer. Two low methylated pectins, LM-5 and LM
      12 were selected for evaluation as drug delivery systems, due to their ability to
      gel in the nasal cavity and their bioadhesive characteristics, together with
      chitosan G210, which acts both as a bioadhesive material and as an efficient
      absorption enhancer. It was found that all of the bioadhesive formulations were
      able to reach the olfactory region in the nasal cavity of human volunteers when
      delivered using a simple nasal drop device. Furthermore, the formulations
      displayed a significantly increased residence time on the epithelial surface.
      This was in contrast to a non-bioadhesive control delivered with the same device.
      In contrast, a pectin formulation administered with a nasal spray system did not
      show an increase in residence time in the olfactory region. It was further shown
      that the reproducibility of olfactory delivery of a polymer formulation was
      significantly better intra-subject than inter-subject.

PMID- 17223023
TI  - [Multifocal infection due to Mycobacterium intracellulare: first case of
      interferon gamma receptor partial dominant deficiency in tropical French
      territory].
AB  - Nontuberculous mycobacterial infections are rare in immunocompetent children, and
      usually present as adenitis. We report a case of a 6-year-old girl with a
      multifocal chronic osteomyelitis and pulmonary localisation due to Mycobacterium
      intracellulare associated with an autosomal dominant mutation of interferon gamma
      receptor 1 gene (INFGR1) leading to a syndrome of mendelian predisposition to
      mycobacteria infections by partial deficiency of intracellular signalisation of
      gamma interferon. This child has been cured with anti-mycobacteria drugs and
      gamma interferon. This report focus on the importance of looking for a
      susceptibility of the host to infectious diseases, which can lead to a specific
      treatment. As far as we know, this is the first case described in a tropical
      area.

PMID- 17223024
TI  - [Cerebral hydatic cyst in children: apropos of 6 cases].

PMID- 17223025
TI  - [One case of Tay-Sachs disease in Gabon].

PMID- 17223026
TI  - Electrocardiography and Wells scoring in predicting the anatomic severity of
      pulmonary embolism.
AB  - Pulmonary embolism (PE) is a major health problem associated with a significant
      morbidity and mortality. Immediate recognition of submassive and massive cases is
      extremely important in order to commencement of early and appropriate therapy
      that could be life saving. The aim of this study was to assess the ability of two
      scoring systems, electrocardiography (ECG) and simplified Wells (sWells) clinical
      scorings in predicting anatomic severity of PE. Hence, ECG and sWells scorings
      were combined in order to test the hypothesis if this new scoring does enhance
      the prediction of severity. Fifty six patients with proven PE with high (50
      patients) and moderate (six patients)-probability of ventilation/perfusion (V/Q)
      scan were retrospectively studied. Baseline ECGs were analysed by two independent
      observers in order to constitute ECG scorings. Baseline sWells scores were also
      calculated. Anatomic severity of PE was calculated by scintigraphically and
      categorized into mild (<50% perfusion defect) (group 1), and severe (50%
      perfusion defect) (group 2) diseases. The mean of ECG scores, sWells scores and
      the combined scores were 5.23+/-3.42 and 5.85+/-3.82; 6.60+/-1.88 and 7.03+/
      2.40; and 10.73+/-3.60 and 11.60+/-4.32 in groups 1 and 2, respectively (p>0.05).
      An ECG score of 6.5 predicted severe disease (perfusion defect 50%) with a
      sensitivity of 41.7% and a specificity of 82%). sWells and combined scores did
      not provide better sensitivity or specificity values based on ROC curve analysis.
      Our results indicated that ECG scoring could be valuable test in predicting
      anatomic severity of PE, adding sWells scoring to ECG scoring did not provide any
      beneficial effect.

PMID- 17223027
TI  - Aetiology in adult patients with bronchiectasis.
AB  - BACKGROUND: Bronchiectasis has a number of causes. Their prevalence is not well
      documented. The aim of this study was to identify aetiology in a population of
      patients referred to a specialist clinic with symptoms suggestive of
      bronchiectasis, to determine the proportion of patients in whom knowing the
      aetiology altered management. In addition we wished to describe in detail those
      patients who remained idiopathic to facilitate future studies of this group; and
      establish the diagnosis in those without bronchiectasis. METHODS: A total of 240
      consecutive patients referred to the Royal Brompton Hospital with a history of
      recurrent chest infections, chronic cough and regular sputum production underwent
      a 3 day program of investigation. RESULTS: A total of 165 patients had
      bronchiectasis on CT scan, an underlying cause was identified in 122 (74%) and
      this affected management in 61 (37%). The common aetiologies were: post-infection
      (52), primary ciliary dyskinesia (17), allergic bronchopulmonary aspergillosis
      (13), and immune deficiency (11). Fourty-three patients had idiopathic
      bronchiectasis. They had symmetrical predominant lower lobe disease with onset of
      chronic chest and sinus symptoms in middle age. CONCLUSION: Full investigation of
      problematic cases should occur in a specialist centre because results affect
      management in a third of cases.

PMID- 17223028
TI  - Evaluation of two- and three-dimensional streptavidin binding platforms for
      surface plasmon resonance spectroscopy studies of DNA hybridization and protein
      DNA binding.
AB  - Surface plasmon resonance (SPR) spectroscopy has been used to study DNA assembly,
      DNA hybridization, and protein-DNA interactions on two streptavidin (SA) sensor
      chips. On one chip, SA molecules are immobilized on a biotin-exposed surface,
      forming an ordered two-dimensional (2D) SA monolayer. The other chip, BIAcore's
      SA chip, contains SA molecules immobilized within a three-dimensional (3D)
      carboxylated dextran matrix. Compared to the 2D chip, the 3D SA matrix allows for
      a slower immobilization rate of biotinylated DNA due to diffusion limitation in
      the dextran matrix, but with twice the amount of the immobilized DNA due to the
      greater number of reactive sites, which in turn enables a higher sensitivity for
      DNA hybridization detection. Interestingly, having a greater DNA probe dispersion
      in the 3D matrix does not induce a higher DNA hybridization efficiency. In a
      study of protein binding to immobilized DNA (estrogen receptor to estrogen
      response elements), aiming at assessing the DNA sequence dependent protein
      binding behavior, the 2D and 3D chips produce different binding characteristics.
      On the 2D chip, the protein binding exhibits a better selectivity to the specific
      sequences, regardless of binding stringency (e.g. salt concentration), whereas on
      the 3D chip, the liquid handling system needs to be optimized in order to
      minimize transport limitations and to detect small affinity differences. Through
      this study we demonstrate that the physicochemical structure of SPR chips affects
      the apparent binding behaviors of biomolecules. When interpreting SPR binding
      curves and selecting a sensor chip, these effects should be taken into account.

PMID- 17223029
TI  - Sensitive reagentless electrochemical immunosensor based on an ormosil sol-gel
      membrane for human chorionic gonadotrophin.
AB  - A new organically modified silicate (ormosil) material was synthesized as a
      matrix to encapsulate enzyme labeled antibody for preparation of immunosensors.
      The ormosil matrix was prepared by hydrolyzing tetraethyoxysilane and (3
      aminopropyl)triethoxysilane in weak alkali solution. It possessed three
      dimensional ordered nanoporous structure with high electrical conductivity and
      good mechanical stability. Its hydrophilicity provided a microenvironment for
      retaining the biological activity of the immobilized protein. Particularly, using
      horseradish peroxidase-labeled human chorionic gonadotrophin antibody (HRP-anti
      hCG) as a model, the immobilized HRP showed direct electron transfer at about -35
      mV with a rate constant of 15.8+/-3.8s(-1). By a simple one-step immunoreaction
      between human serum chorionic gonadotrophin (hCG) in sample solution and the
      immobilized HRP-anti-hCG, the differential pulse voltammetric peak current of HRP
      decreased linearly with an increasing hCG concentration from 0.5 to 50 mIU/ml
      with a relatively low limit of detection of 0.3 mIU/ml at 3sigma. Excellent
      analytical performance, fabrication reproducibility and operational stability of
      the proposed biosensor indicated its promising application in clinical
      diagnostics.

PMID- 17223030
TI  - Evaluation of the analytical performances of avidin-modified carbon sensors based
      on a mediated horseradish peroxidase enzyme label and their application to the
      amperometric detection of nucleic acids.
AB  - In this study, neutravidin-coated screen-printed carbon sensors were fully
      characterized and further used for the amperometric detection of specific DNA
      sequences of human cytomegalovirus (HCMV DNA). For this purpose, we took
      advantage of an earlier established relationship between the amount of HRP
      affinity immobilized on the surface of the electrode and the steady-state current
      recorded in the presence of H(2)O(2) as substrate and the single electron donor
      [Os(III)(bpy)(2)pyCl](2+) as cosubstrate. After incubating a saturating
      concentration of biotinylated horseradish peroxidase (Bio-HRP) onto the
      neutravidin-modified sensors, a surface concentration of active HRP of 3.6 pmol
      cm(-2) was calculated from the measurement of the electrocatalytic plateau
      current value. This result indicates that monolayers of neutravidin were adsorbed
      on the screen-printed carbon sensors. These neutravidin-covered platforms were
      then used to immobilize biotinylated nucleic acid targets. After hybridization
      with a complementary digoxigenin-labeled detection probe, the extent of hybrids
      formed was determined with an anti-digoxigenin HRP conjugate. The biosensor assay
      was applied to the detection of a synthetic oligonucleotide target, and then to
      the determination of an amplified viral DNA sequence. Monolayers of HRP-labeled
      oligonucleotide hybrids were immobilized onto the sensing surface whereas one
      third of the surface was covered with HCMV DNA hybrids. On the other hand,
      detection limits of 200 pM and 1 nM were obtained for the short oligonucleotide
      and the longer DNA targets, respectively. Finally, we demonstrated that the
      sensitivity of the electrochemical assay could be significantly improved by using
      high concentrations of the reduced form of the mediator [Os(II)(bpy)(2)pyCl](+),
      thus allowing one to detect as low as 30 pM of amplified HCMV DNA fragment.

PMID- 17223031
TI  - Microbial fuel cell-based biosensor for fast analysis of biodegradable organic
      matter.
AB  - The current study was made to develop a biosensor based on a single-chamber
      microbial fuel cell in which anaerobes were retained in the anode compartment
      separated from the cathode compartment by a proton exchange membrane. In the
      sensor a replaceable anaerobic consortium was used for analyzing biodegradable
      organic matter. The anaerobes acted as biocatalysts in oxidizing organic matter
      and transferring electrons to the anode. The biocatalysts were renewed for each
      sample analysis by replacing the old anaerobic consortium with an equal amount of
      fresh one. A glucose standard solution was used as the target substrate. To
      obtain the maximum sensor output, the MFC-based sensor system was optimized using
      an 800 Omega resistor as the load to the external electric circuit and 25 mM
      phosphate buffer with 50mM NaCl as catholyte in the aerobic compartment. The
      temperature of anaerobic compartment was maintained at optimal 37 degrees C. The
      cell potential across the electrodes increased with increasing loading of
      glucose. The sensor response was linear against concentration of glucose up to 25
      gl(-1). The detection limit was found as 0.025 gl(-1). The microbial fuel cell
      with replaceable anaerobic consortium could be used as a biosensor for on-line
      monitoring of organic matter.

PMID- 17223032
TI  - Portable 24-analyte surface plasmon resonance instruments for rapid, versatile
      biodetection.
AB  - Field use of surface plasmon resonance (SPR) biosensors for environmental and
      defense applications such as detection and identification of biological warfare
      agents has been hampered by lack of rugged, portable, high-performance
      instrumentation. To meet this need, we have developed compact multi-analyte SPR
      instruments based on Texas Instruments' Spreeta sensing chips. The instruments
      weigh 3 kg and are built into clamshell enclosures measuring 28 cm x 22 cm x 13
      cm. Functions are divided between an electronics unit in the base of the box and
      a fluidics assembly in the lid. Automated valves and pumps implement an injection
      loop flow system that allows sensors to be exposed to sample, rinsed, and treated
      with additional reagents (such as secondary antibodies) under computer control.
      Injected samples flow over the surfaces of eight sensor chips fastened into a
      temperature-controlled silicone flowcell. Each chip has 3 sensing regions, for a
      total detection of 24 areas that can be simultaneously monitored by SPR. Coating
      these areas with appropriate antibodies or other receptors allows a sample to be
      screened for up to 24 different substances simultaneously. The instruments report
      refractive index (RI) values every second, with a typical noise level of 1-3 x
      10(-6) RI units. The design of the device is described, and performance is
      illustrated with detection of six distinct analytes ranging from small molecules
      to whole microbes during the course of a single experiment.

PMID- 17223033
TI  - The role of extracellular matrix in CNS regeneration.
AB  - Chondroitin sulfate proteoglycans are the principal inhibitory component of glial
      scars, which form after damage to the adult central nervous system and act as a
      barrier to regenerating axons. Recent findings have furthered our understanding
      of the mechanisms that result in a failure of regeneration after spinal cord
      injury and suggest that a multipartite approach will be required to facilitate
      long-distance regeneration and functional recovery.

PMID- 17223035
TI  - Industry or academia: Who leads the research in medicine?

PMID- 17223036
TI  - The diagnosis and treatment of male osteoporosis: Defining, assessing, and
      preventing skeletal fragility in men.
AB  - Male osteoporosis is associated with a significant burden in terms of morbidity,
      mortality, and economic cost. Despite recent advances in the understanding of the
      male osteoporotic syndrome, the evaluation and treatment of men suffering from
      osteoporosis remains a clinical challenge. In men with osteoporosis, it remains
      particularly critical to exclude underlying pathological causes as these are much
      more likely to be present than in women. There is increasing evidence that the
      approaches developed to diagnose and treat the disorder in women may be equally
      useful in men. The available evidence suggests that the anti-fracture efficacy of
      treatment with alendronate, risedronate, or teriparatide is similar in both
      sexes. Additional research is warranted to prospectively address the usefulness
      of BMD measurements to predict fracture risk, to identify those men who are
      likely to benefit the most from therapy, and to monitor individual responses to
      therapy.

PMID- 17223037
TI  - Thiazolidinediones for the treatment of type 2 diabetes.
AB  - Thiazolidinediones (TZD), or glitazones, represent a new generation of
      antidiabetic drugs that have recently been introduced in Europe. They improve
      insulin resistance, one of the key anomalies involved in the pathogenesis of type
      2 diabetes mellitus, by activating the nuclear peroxoxisome proliferator
      activated receptor-gamma (PPAR-gamma), leading to crucial metabolic alterations
      in adipose tissue. Rosiglitazone and pioglitazone have been shown to be active as
      monotherapy, in combination therapy with metformin or sulfonylureas, and even in
      triple therapy. They are generally well tolerated but can induce fluid retention.
      Cardiac failure is a contraindication for the use of TZDs, as is the concomitant
      administration of insulin. Aside from their effect on glycemic control, TZDs act
      on several cardiovascular risk factors and may protect pancreatic beta cells from
      apoptosis. The cardiovascular protective effect of TZDs has recently been
      demonstrated with the results of the PROactive study, and long-term preservation
      of beta-cell function is currently under further investigation.

PMID- 17223038
TI  - The history of the (Young) AEMI(E) and the EFIM.
AB  - The European Federation of Internal Medicine (EFIM) was formed in 1996 through a
      merger between the Association Europeenne de Medicine Interne (d' Ensemble)
      (AEMI(E)) and the Forum of Presidents of National Societies of Internal Medicine
      (IM). It arose as a result of ideas from Carcassi (Rome/Cagliari) and Merino
      (Alicante) to transform the largely French-speaking and rather elitist AEMI into
      a more easily accessible and English-speaking federation of national societies.
      The founding meeting of the General Assembly of the EFIM took place in May 1996
      in Paris. Since then, the EFIM has initiated many activities, some of them
      originating from the time of the AEMI(E).

PMID- 17223039
TI  - Use of the median for the evaluation of blood pressure self-measurement (BPSM).
AB  - BACKGROUND: One of the disadvantages of blood pressure self-measurement (BPSM) is
      that it requires doctors to carry out cumbersome calculations involving a large
      number of figures during the medical visit. Here, we compare the use of median
      blood pressure values to mean blood pressure values as a diagnostic criterion for
      home BPSM. METHODS: Self-measurements from 253 patients (51.1+/-12.2 years, 48%
      male and 52% female) were collected. Sixty-two percent of these patients were
      receiving antihypertensive treatment. Each patient was given an OMROM 705 monitor
      to carry out the blood pressure measurements at home. A total of 12 measurements
      were taken, 2 in the morning and 2 in the afternoon for 3 consecutive days. The
      mean and median values were calculated for each patient. RESULTS: The median SBP
      (143.04+/-18.53 mmHg) did not differ from the mean SBP (143.1+/-18.85 mmHg). The
      same was true for DBP (median 82.25+/-9.56; mean 82.26+/-9.39 mmHg). There were
      no significant differences in the classification of the patients with regard to
      whether the median or the mean was used. Some 47.3% of the measurements had a
      mean SBP below 135 and 79.8% had a mean DBP below 85 mmHg. Using the median, SBP
      was below 135 in 48.4% of the cases and DBP below 85 in 82.01% of the cases.
      Differences were not significant. The sensitivity of the median for SBP was 97.0%
      and the specificity was 97.0%. False-positives were 1.60% and false-negatives
      1.18%. The sensitivity of the median for DBP was 94.0% and the specificity was
      97.0%. False-positives were 1.18% and false-negatives 3.95%. The kappa
      coefficient was 0.994 for SBP and 0.882 for DBP. CONCLUSIONS: The median seems to
      be a valid alternative to the mean in the evaluation of BPSN results, offering
      good sensitivity and specificity and greater ease of use in daily practice.

PMID- 17223040
TI  - Unconscious defensive medicine: The case of erythrocyte sedimentation rate.
AB  - BACKGROUND: We investigated physician rationale for and against performing
      routine erythrocyte sedimentation rate (ESR) tests during hospital admissions.
      METHODS: A comparative, descriptive, prospective study among 82 physicians in 15
      departments of internal medicine from two University Medical Centers - A and B -
      in Israel was conducted between July and August 2004. Reasons for physicians' use
      of ESR were examined using a confidential questionnaire. A panel of four experts
      reviewed the need to perform an ESR test in 100 patients' files from center B.
      The main outcome measures were the use of ESR in routine hospital admissions and
      reasons for use. RESULTS: Forty-four vs. zero physicians from medical centers B
      and A, respectively, routinely perform ESR tests for all admitted patients
      (p<0.001). According to the experts, in only 10-30% of the 67 new patients could
      ESR tests have been of some value. Reasons for performing ESR routinely were as
      follows: to identify severe and "hidden" diseases (21/44, 47.7%); because it is
      crucial for all patients, both new and returning (10/44, 22.7%); because it is a
      guideline from department head (6/44, 13.6%); it is recommended in the literature
      (5/44, 11.4%); don't know why (2/44, 4.5%); defensive medicine (1/44, 2.3%); and
      other (6/44, 13.6%). CONCLUSION: Routine use of ESR tests on admission can be
      explained by old habits and by an unconscious concern about liability, i.e.,
      unconscious defensive medicine.

PMID- 17223041
TI  - Cardiovascular risk factors after bariatric surgery: Do patients gain more than
      expected from their substantial weight loss?
AB  - BACKGROUND: While it has been established that even limited weight loss (5-10%)
      improves obesity-associated cardiovascular risk factors, it is not known if
      considerable weight loss following laparoscopic adjustable silicone gastric
      banding (LASGB) results in a cardiovascular risk profile that is comparable,
      worse, or even better than that of matched control subjects. METHODS:
      Cardiovascular risk factors were compared in three groups of 24 women each: an
      index group that had lost considerable weight following LASGB for morbid obesity
      (BMI>40 kg/m(2)), a control group with the same BMI that the index group achieved
      after weight loss, and a pre-weight loss group of women with a BMI above 40
      kg/m(2). Anthropometric measures, fasting serum glucose, insulin, lipids, C
      reactive protein, and homocysteine levels were determined and insulin sensitivity
      was estimated using a homeostasis model assessment index (HOMA-IR). RESULTS:
      After bariatric surgery, the index group had a BMI of 32.0+/-0.8 kg/m(2). This
      resulted in a significantly better cardiovascular risk profile than that of the
      pre-weight loss group (BMI 42.8+/-0.6 kg/m(2)). Unexpectedly, after weight loss,
      the index group had significantly lower systolic blood pressure, fasting serum
      insulin, and HOMA-IR than the BMI-matched (32.8+/-0.9 kg/m(2)) control group.
      Although not significant, diastolic blood pressure, LDL-cholesterol, and CRP
      levels were also lower. CONCLUSION: Considerable weight loss following bariatric
      surgery leads to a greater improvement in cardiovascular risk factors than might
      be expected from the weight loss.

PMID- 17223042
TI  - Abdominal tenderness in ascites patients indicates spontaneous bacterial
      peritonitis.
AB  - BACKGROUND: Spontaneous bacterial peritonitis (SBP), which has been reported to
      be present in 10-30% of patients with cirrhotic ascites, may easily be
      overlooked. An important aim of our study was to determine whether there are any
      clinical signs which, in clinical practice, may predict or exclude SBP. METHODS:
      We studied 133 patients with cirrhotic ascites from medical units at nine Swedish
      university hospitals where there had been at least one diagnostic ascites tap
      with analysis of polymorphonuclear leukocytes in the ascites fluid. The patients
      had initially been questioned about background factors and physically examined
      according to a standardized case record form. Samples of blood, urine, and
      ascites were then drawn for analysis according to a structured schedule. RESULTS:
      SBP could be excluded in 80% of all the cases and was confirmed in 8% of the 133
      patients in the final analysis. Abdominal pain and abdominal tenderness were more
      common in patients with SBP (p<0.01), but no other physical sign or laboratory
      test could separate SBP cases from the others. CONCLUSIONS: SBP was present in
      about one-tenth of the hospitalized patients with cirrhotic ascites in this
      cohort. Performing repeated physical examinations and paying particular attention
      to abdominal tenderness may be the best way to become aware of the possible
      development of this complication.

PMID- 17223043
TI  - Risk factors associated with HCV infection in semi-rural areas of central Greece.
AB  - BACKGROUND: Hepatitis C virus (HCV) appears to be endemic in most parts of the
      world, but there is considerable geographic variation. In order to assess the
      geographic distribution of HCV in Thessaly, in central Greece, we conducted a
      retrospective study in HCV-infected patients attending the Academic Liver Unit of
      Thessaly University from 1999 to 2003. We also investigated whether variation
      among regions could be attributed to differences in risk factors. METHODS: We
      evaluated the records of 309 HCV patients whose origin and/or residence was in
      Thessaly. To identify risk factors that were independently associated with the
      place of birth and/or residence, adjusted odds ratios (OR) were calculated by
      logistic regression analysis. We also studied the medical records of 150 HCV
      negative patients from the same areas in order to evaluate whether there are
      differences in risk factors reported by HCV-positive and HCV-negative patients.
      RESULTS: We found three municipalities with a high HCV frequency. The use of non
      disposable, multiple-use glass syringes for medical purposes in the past was the
      only potential risk factor more frequently identified in these areas than in
      other places (OR=2.3; p<0.05). This risk factor was significantly (p<0.001)
      associated with older age of the infected patients. CONCLUSIONS: This study shows
      that the spread of HCV in the three regions may have occurred several years ago
      as a result of the use of multiple-use glass syringes. Differences in prevalence
      rates among different age groups, as well as among different areas, indicate the
      need for extensive studies to determine HCV epidemiology and to develop
      appropriate prevention programs.

PMID- 17223044
TI  - Basal insulin or premix analogue therapy in type 2 diabetes patients.
AB  - BACKGROUND: We sought to compare the safety and efficacy of biphasic insulin
      aspart 30 (BIAsp 30) given twice daily with once-daily insulin glargine in
      patients with type 2 diabetes beginning insulin therapy and who did not use
      thiazolidinediones, which are contraindicated with insulin in the European Union,
      in a subpopulation (N=157) of the INITIATE study. METHODS: At baseline, HbA(1c)
      was >/=8.0% on >/=1000 mg/day metformin alone or in combination with other oral
      antidiabetic drugs (OADs; e.g. sulphonylurea or alpha-glucosidase inhibitors).
      Metformin was adjusted up to 2550 mg/day and other OADs were discontinued.
      Starting insulin doses were subsequently adjusted weekly for 26 weeks by
      algorithm-directed titration. RESULTS: The proportion of patients achieving a
      HbA(1c) below 7.0% at 28 weeks was greater with BIAsp 30 than with insulin
      glargine (65% vs 41%, P=0.003). The mean reduction in HbA(1c) was greater for
      BIAsp 30 than for insulin glargine: -2.89+/-1.6% vs -2.46+/-1.6%, respectively
      (P=0.035). Postprandial glucose increments were lower for the BIAsp 30 group
      after breakfast (P=0.003) and dinner (P=0.033); post-lunch values were not
      significantly different. No major hypoglycemic episodes were recorded. Nocturnal
      hypoglycemia was reported by 25% of subjects in the BIAsp 30 group and by 10% in
      the insulin glargine group (P=0.021). Weight gain was 5.6+/-4.6 and 3.0+/-4.3 kg
      (P=0.0004) for BIAsp 30 and insulin glargine, respectively. CONCLUSIONS: BIAsp
      30, given twice daily in combination with metformin, was more effective than
      insulin glargine, given once daily in combination with metformin, at controlling
      blood glucose in insulin-naive patients with type 2 diabetes, but was associated
      with increased weight gain and minor hypoglycemic events.

PMID- 17223045
TI  - Mitral valve reconstruction with unusual bleeding complications.
AB  - With the surgical techniques used nowadays, bleeding complications after heart
      surgery have become less common. We report the case of a 72-year-old male patient
      who underwent mitral valve reconstruction and suffered from serious bleeding
      complications. The patient needed repeated blood transfusions (30 red blood cell
      concentrates and 12 units of fresh frozen plasma) until a final diagnosis of
      hemophilia A was made and substitution of the depleted factor VIII was begun.

PMID- 17223046
TI  - Psoas abscess: An unusual manifestation of Q fever.
AB  - Q fever may lead to serious complications in chronically infected patients. We
      report two cases of psoas abscess due to Coxiella burnetii associated with lumbar
      osteomyelitis secondary to an aortic aneurysmal infection. Diagnosis was based on
      serology, and PCR detected C. burnetii DNA in an abscess sample.

PMID- 17223047
TI  - Desensitization therapy in a patient with furosemide allergy.
AB  - Allergy to furosemide is a rare phenomenon. Desensitization to this sulfa
      containing drug has not been frequently performed. We describe a patient with
      severe congestive heart failure and type I allergy to furosemide. Because of the
      severity of her condition, we decided to use a rapid intravenous desensitization
      protocol. Following the desensitization, the patient was treated with intravenous
      and oral furosemide with a dramatic improvement in her clinical state. We suggest
      that rapid desensitization may be a safe and effective way of introducing
      furosemide to allergic patients for whom loop diuretics are urgently indicated.

PMID- 17223048
TI  - A centrofacial B lymphoma in a rheumatoid arthritis patient.
AB  - We report on a 65-year-old man who was hospitalized for polyarthritis with
      deterioration of his general state of health and chronic sinusitis. Clinical and
      biological signs led to the diagnosis of RA associated with localized Wegener's
      granulomatosis. Methotrexate and corticosteroids led to a distinct improvement in
      the patient's articular symptoms and in his general condition. One year after the
      start of treatment, a tumefaction of the right maxillary sinus appeared. Scans
      revealed a tumoral lesion in the right maxillary sinus. This proved to be a large
      B-cell lymphoma. The patient received chemotherapy (CHOP) and radiotherapy. This
      centrofacial lymphoma may be regarded as a B lymphoma of the MALT (mucosal
      associated lymphoma tumor) type, mimicking a relapse of Wegener's granulomatosis.

PMID- 17223049
TI  - Atrial myxoma presenting with total occlusion of the abdominal aorta and multiple
      peripheral embolism.
AB  - Cardiac myxoma is a rare disease with a variety of nonspecific clinical
      manifestations. Embolic phenomenon is a well-known entity. However, total
      occlusion of the descending aorta by saddle embolus is very unusual. We report a
      patient with cardiac myxoma who presented with acute onset of bilateral lower
      limb ischemia and total occlusion of the abdominal aorta by a large saddle
      embolus.

PMID- 17223050
TI  - Dramatic effect of sirolimus on renal angiomyolipomas in a patient with tuberous
      sclerosis complex.
AB  - Angiomyolipomas are very common in patients with tuberous sclerosis complex (TSC)
      and cause substantial morbidity. Until now, arterial embolization has been the
      recommended treatment for symptomatic patients. We report the case of a woman
      with TSC and giant angiolipomas in whom sirolimus induced a dramatic reduction in
      bilateral renal tumors.

PMID- 17223051
TI  - Duplicated papers and other inappropriate behavior.

PMID- 17223052
TI  - Treatment with piperacillin-tazobactam and Aspergillus galactomannan test results
      for patients with hematological malignancies.

PMID- 17223053
TI  - Polyarticular septic arthritis caused by Streptococcus pyogenes in an
      immunocompetent woman.

PMID- 17223054
TI  - Acute hepatitis associated with the use of Ma-huang in a young adult.

PMID- 17223055
TI  - Migration of appendicolith to skin, a late complication of appendicectomy.

PMID- 17223057
TI  - Current concepts in normal and abnormal puberty.

PMID- 17223059
TI  - Is there a general task switching ability?
AB  - Participants were tested on two analogous task switching paradigms involving
      Shape/Size tasks and Vertical/Horizontal tasks, respectively, and three measures
      of psychometric intelligence, tapping fluid, crystallized and perceptual speed
      abilities. The paradigms produced similar patterns of group mean reaction times
      (RTs) and the vast majority of the participants showed switching cost (switch RT
      minus repeat RT), mixing cost (repeat RT minus single-task RT) and congruency
      effects. The shared intra-individual variance across paradigms and with
      psychometric intelligence served as criteria for general ability. Structural
      equations modeling indicated that switching cost with ample preparation
      ("residual cost") and mixing cost met these criteria. However, switching cost
      with little preparation and congruency effects were predominantly paradigm
      specific.

PMID- 17223060
TI  - Formation, stability and properties of multilayer emulsions for application in
      the food industry.
AB  - The formation of multilayered interfaces around oil droplets in oil-in-water
      emulsions provides food technologists with a novel means of improving the quality
      and stability of many food products, as well as the ability to develop novel
      encapsulation and delivery systems. This article reviews the basic principles of
      multilayer emulsion formation, discusses the factors that influence the
      characteristics of the interfaces formed, and highlights the relationship between
      interfacial properties and emulsion functionality. Finally, it highlights some
      potential applications of the multilayer emulsion technology in the food industry
      for improving the stability of emulsions to environmental stresses or for
      developing controlled or triggered release systems.

PMID- 17223061
TI  - "Instant vision" compared with postoperative patching: clinical evaluation and
      patient satisfaction after bilateral cataract surgery.
AB  - PURPOSE: To compare two methods of postoperative dressing regimen: patching vs
      "instant vision" without patch. DESIGN: Prospective randomized clinical trial.
      METHODS: Sixty consecutive hospitalized, nonambulatory patients with cataract
      surgery under topical anesthesia on both eyes at different days were enrolled
      prospectively. In randomized order, one eye was patched for the first 24 hours
      postoperatively; the other eye was left open without patch to obtain "instant
      vision." Both eyes received the same anti-inflammatory and antibiotic drop
      therapy. RESULTS: Twenty-four hours postoperatively, no significant differences
      between patching and "instant vision" could be found for corrected and
      uncorrected visual acuity, corneal epithelial defects, conjunctival inflammation,
      anterior chamber flare, and intraocular pressure (P > .05). During the first 24
      hours postoperatively, all tear film parameters were significantly worse in the
      "instant vision" eyes (P < .001), indicating a transient tear film instability.
      During the first four hours after cataract surgery, pain scores in the "instant
      vision" eyes were significantly higher than in the patched eyes (P < .001). Eight
      hours postoperatively and later, there were no significant differences in any
      pain scores (P > .05). After experiencing both methods, 27% of the patients
      subjectively rated the two methods as equivalent; 8% of the patients preferred
      "instant vision." Despite of the benefits of immediately improved orientation,
      65% of the tested patients preferred patching to "instant vision" because of
      lower pain and foreign body sensations and psychologic arguments. CONCLUSIONS:
      The clinical examinations showed that both methods were equally safe for
      postoperative therapy. However, further efforts have to be made to increase the
      patients' comfort with "instant vision" in the first hours after cataract
      surgery.

PMID- 17223062
TI  - Monitoring the homogeneity of adenovirus preparations (a gene therapy delivery
      system) using analytical ultracentrifugation.
AB  - This study explores the capability of modern analytical ultracentrifugation (AUC)
      to characterize the homogeneity, under product formulation conditions, of
      preparations of adenovirus vectors used in gene therapy and to assess the lot-to
      lot consistency of this unique drug product. We demonstrate that a single
      sedimentation velocity run on an adenovirus sample can detect and accurately
      quantify a number of different forms of virus particles and subvirus particles.
      These forms include (a) intact virus monomer particles, (b) virus aggregates, (c)
      empty capsids (ECs), and (d) smaller assembly intermediates or subparticles
      formed during normal or aberrant virus assembly (or as a result of damage to the
      intact adenovirus or EC material during all phases of virus production). This
      information, which is collected on adenovirus samples under the exact formulation
      conditions that exist in the adenovirus vial, is obtained by direct boundary
      modeling of the AUC data generated from refractometric and/or UV detection
      systems using the computer program SEDFIT developed by Peter Schuck. Although
      both detectors are useful, refractometric detection using the Rayleigh
      interferometer offers a key advantage for providing accurate concentration
      information due to the similar response factors for both protein and DNA and its
      insensitivity to light scattering effects. Additional AUC data obtained from
      analytical band sedimentation velocity and density gradient sedimentation
      equilibrium experiments in CsCl with UV detection were also generated. These
      results further support conclusions concerning the solution properties of
      adenovirus, the identity of the different virus species, and the overall
      capability of boundary sedimentation velocity analysis.

PMID- 17223063
TI  - Detection of proteins based on amino acid sequences by multiple aptamers against
      tripeptides.
AB  - A number of different ligands have been tested in the course of the development
      of protein array technology. The most extensively studied example of protein
      ligands has been based on antibody-antigen interaction. Other examples include
      protein-protein, protein-nucleic acid, and protein-small molecule interactions.
      All these ligands can recognize and specifically bind to protein epitopes. In
      this study, we have developed a novel technology using DNA-based aptamers to
      detect proteins based on their amino acid sequences. Mouse cathepsin D was used
      for the proof of principle experiment. Four tripeptides, Leu-Ala-Ser, Asp-Gly
      Ile, Gly-Glu-Leu, and Lys-Ala-Ile, were selected based on the published amino
      acid sequence of mouse cathepsin D. DNA aptamers against the tripeptides were
      isolated using the systematic evolution of ligands of exponential enrichment
      method. We have demonstrated that the aptamers specifically interacted with mouse
      cathepsin D using the structure-switch method. We further performed a proximity
      dependent ligation assay to demonstrate that multiple aptamers could specifically
      detect the protein from cell extracts. In principle, one library containing 8000
      aptamers should be enough to detect almost all proteins in the whole proteome in
      all organisms. This technology could be applied to generate a new generation of
      protein arrays.

PMID- 17223064
TI  - Quantification of alpha-lactalbumin in human milk: method validation and
      application.

PMID- 17223065
TI  - Endotoxin detection in a competitive electrochemical assay: synthesis of a
      suitable endotoxin conjugate.
AB  - A biotin-lipopolysaccharide (biotin-LPS) conjugate was synthesized from LPS
      smooth from Salmonella minnesota, yielding a conjugate with a biotin/LPS ratio
      equal to 1:1 and endotoxic activity of 0.08 EU ng(-1). The conjugate was used in
      an amperometric competitive assay to determine endotoxins with endotoxin
      neutralizing protein (ENP) as the recognition element. The assay is performed on
      a modified electrode, involving the covalent binding of carboxymethyl dextran
      (CMDex) to a cystamine-modified gold electrode and then the covalent binding of
      the recognition protein, ENP, to CMDex. The assay is carried out by incubating
      the modified electrode in an LPS sample to which biotin-LPS was added. Both
      species compete for the recognition sites on the modified surface. After the
      incubation stage and a careful rinsing, the electrode is immersed in a solution
      containing neutravidin-horseradish peroxidase conjugate (N-HRP), which binds to
      the sites containing biotin-LPS on the electrode. The system is rinsed and a
      current signal is generated by the addition of hydrogen peroxide and a redox
      mediator. The assay is able to detect LPS from Salmonella minnesota at
      concentrations as low as 0.1 ng ml(-1), equivalent to 0.07 EU ml(-1).

PMID- 17223066
TI  - Demonstration of mitochondrial oestrogen receptor beta and oestrogen-induced
      attenuation of cytochrome c oxidase subunit I expression in human periodontal
      ligament cells.
AB  - OBJECTIVE: Periodontal ligament (PDL) cells express oestrogen receptor beta
      (ERbeta) protein, but cellular functions regulated by ERbeta in these cells have
      not been identified. In this study we determine if ERbeta is localised to
      mitochondria and if oestrogen regulates mitochondrial function in human PDL cells
      obtained from teeth extracted for orthodontic reasons. DESIGN: Subcellular
      distribution of ERbeta was determined by confocal microscopy of cells co-stained
      with ERbeta antibody and the mitochondrion-selective probe MitoTracker and by
      immunogold electron microscopy. Expression of the mitochondrial enzyme cytochrome
      c oxidase subunit I, involved in oxidative phosphorylation, was determined by
      Western blotting in cells treated with or without physiological concentrations of
      the endogenous oestrogen 17beta-oestradiol. RESULTS: ERbeta immunoreactivity was
      observed both in the nuclei and the cytoplasm. MitoTracker-labelling was observed
      in the cytoplasm, especially in the perinuclear region, but not in the nuclei. Co
      localisation of ERbeta and MitoTracker was observed in cells derived from both
      male and female subjects. Mitochondrial localisation of ERbeta was confirmed by
      immunogold electron microscopy. Cells treated with or without 17beta-oestradiol
      (100 nM) displayed an identical pattern of staining for mitochondria. Treatment
      with 100 nM 17beta-oestradiol attenuated cytochrome c oxidase subunit I
      expression by about 30%, while combined treatment with 17beta-oestradiol and the
      ER blocker ICI 182780 (10 microM) had no effect. CONCLUSION: This study
      demonstrates mitochondrial localisation of ERbeta and oestrogen-induced decrease
      in the expression of cytochrome c oxidase subunit I in human PDL cells,
      suggesting that oestrogen probably via ERbeta influences mitochondrial function
      and PDL cell energy metabolism.

PMID- 17223067
TI  - Modulation operated by the sympathetic nervous system on jaw reflexes and
      masticatory movement.
AB  - The sympathetic nervous system (SNS), that is activated under condition of
      physical, psychological and psychosocial stress, affects force production and
      fatigability of muscles by controlling both muscle blood flow and the
      intracellular contractile mechanism. In addition SNS may affect motor function by
      modulating afferent activity from muscle spindles that are highly concentrated in
      jaw-closing muscles. Possible implications of these actions on masticatory
      function and myofascial pain are discussed.

PMID- 17223068
TI  - Chromatic photoacclimation, photosynthetic electron transport and oxygen
      evolution in the chlorophyll d-containing oxyphotobacterium Acaryochloris marina.
AB  - Changes in photosynthetic pigment ratios showed that the Chlorophyll d-dominated
      oxyphotobacterium Acaryochloris marina was able to photoacclimate to different
      light regimes. Chl d per cell were higher in cultures grown under low irradiance
      and red or green light compared to those found when grown under high white light,
      but phycocyanin/Chl d and carotenoid/Chl d indices under the corresponding
      conditions were lower. Chl a, considered an accessory pigment in this organism,
      decreased respective to Chl d in low irradiance and low intensity non-white light
      sources. Blue diode PAM (Pulse Amplitude Modulation) fluorometry was able to be
      used to measure photosynthesis in Acaryochloris. Light response curves for
      Acaryochloris were created using both PAM and O(2) electrode. A linear
      relationship was found between electron transport rate (ETR), measured using a
      PAM fluorometer, and oxygen evolution (net and gross photosynthesis). Gross
      photosynthesis and ETR were directly proportional to one another. The optimum
      light for white light (quartz halogen) was about 206+/-51 micromol m(-2) s(-1)
      (PAR) (Photosynthetically Active Radiation), whereas for red light (red diodes)
      the optimum light was lower (109+/-27 micromol m(-2) s(-1) (PAR)). The maximum
      mean gross photosynthetic rate of Acaryochloris was 73+/-7 micromol mg Chl d(-1)
      h(-1). The gross photosynthesis/respiration ratio (P(g)/R) of Acaryochloris under
      optimum conditions was about 4.02+/-1.69. The implications of our findings will
      be discussed in relation to how photosynthesis is regulated in Acaryochloris.

PMID- 17223069
TI  - Subsequent events to GTP binding by the plant PsbO protein: structural changes,
      GTP hydrolysis and dissociation from the photosystem II complex.
AB  - Besides an essential role in optimizing water oxidation in photosystem II (PSII),
      it has been reported that the spinach PsbO protein binds GTP [C. Spetea, T.
      Hundal, B. Lundin, M. Heddad, I. Adamska, B. Andersson, Proc. Natl. Acad. Sci.
      U.S.A. 101 (2004) 1409-1414]. Here we predict four GTP-binding domains in the
      structure of spinach PsbO, all localized in the beta-barrel domain of the
      protein, as judged from comparison with the 3D-structure of the cyanobacterial
      counterpart. These domains are not conserved in the sequences of the
      cyanobacterial or green algae PsbO proteins. MgGTP induces specific changes in
      the structure of the PsbO protein in solution, as detected by circular dichroism
      and intrinsic fluorescence spectroscopy. Spinach PsbO has a low intrinsic GTPase
      activity, which is enhanced fifteen-fold when the protein is associated with the
      PSII complex in its dimeric form. GTP stimulates the dissociation of PsbO from
      PSII under light conditions known to also release Mn(2+) and Ca(2+) ions from the
      oxygen-evolving complex and to induce degradation of the PSII reaction centre D1
      protein. We propose the occurrence in higher plants of a PsbO-mediated GTPase
      activity associated with PSII, which has consequences for the function of the
      oxygen-evolving complex and D1 protein turnover.

PMID- 17223070
TI  - Pharmacokinetics of poly(hydroxyethyl-l-asparagine)-coated liposomes is superior
      over that of PEG-coated liposomes at low lipid dose and upon repeated
      administration.
AB  - 'Stealth' liposomes with a poly(ethylene glycol) (PEG) coating are frequently
      studied for drug delivery and diagnostic purposes because of their prolonged
      blood circulation kinetics. However, several recent reports have demonstrated
      that PEG-liposomes are rapidly cleared at single low lipid doses (<1 micromol/kg)
      and upon repeated administration (time interval between the injections 5 days-4
      weeks). Recently, poly(amino acid)-based stealth liposome coatings have been
      developed as alternative to the PEG-coating. In this study, the pharmacokinetic
      behavior of liposomes coated with the poly(amino acid) poly(hydroxyethyl-l
      asparagine) (PHEA) was evaluated at low lipid doses and upon repeated
      administration in rats. Blood circulation times and hepatosplenic localization of
      PHEA-liposomes were assessed after intravenous injection. When administered at a
      dose of 0.25 micromol/kg or less, PHEA-liposomes showed significantly longer
      blood circulation times than PEG-liposomes. A second dose of PHEA-liposomes 1
      week after the first injection was less rapidly cleared from the circulation than
      a second dose of PEG-liposomes. Although the mechanisms behind these observations
      are still not clear yet, the use of PHEA-liposomes appears beneficial when single
      low lipid doses and/or repeated dosing schedules are being applied.

PMID- 17223071
TI  - Transmembrane helices of membrane proteins may flex to satisfy hydrophobic
      mismatch.
AB  - A novel mechanism for membrane modulation of transmembrane protein structure, and
      consequently function, is suggested in which mismatch between the hydrophobic
      surface of the protein and the hydrophobic interior of the lipid bilayer induces
      a flexing or bending of a transmembrane segment of the protein. Studies on model
      hydrophobic transmembrane peptides predict that helices tilt to submerge the
      hydrophobic surface within the lipid bilayer to satisfy the hydrophobic effect if
      the helix length exceeds the bilayer width. The hydrophobic surface of
      transmembrane helix 1 (TM1) of lactose permease, LacY, is accessible to the
      bilayer, and too long to be accommodated in the hydrophobic portion of a typical
      lipid bilayer if oriented perpendicular to the membrane surface. Hence, nuclear
      magnetic resonance (NMR) data and molecular dynamics simulations show that TM1
      from LacY may flex as well as tilt to satisfy the hydrophobic mismatch with the
      bilayer. In an analogous study of the hydrophobic mismatch of TM7 of bovine
      rhodopsin, similar flexing of the transmembrane segment near the conserved NPxxY
      sequence is observed. As a control, NMR data on TM5 of lacY, which is much
      shorter than TM1, show that TM5 is likely to tilt, but not flex, consistent with
      the close match between the extent of hydrophobic surface of the peptide and the
      hydrophobic thickness of the bilayer. These data suggest mechanisms by which the
      lipid bilayer in which the protein is embedded modulates conformation, and thus
      function, of integral membrane proteins through interactions with the hydrophobic
      transmembrane helices.

PMID- 17223072
TI  - Perception of arousal in social anxiety: effects of false feedback during a
      social interaction.
AB  - Cognitive models suggest that during social interactions, socially anxious
      individuals direct their attention to internal cues of arousal and use this
      information to erroneously infer how they appear to others. High (N=36) and low
      (N=36) socially anxious adults had a conversation with a stooge, and were led to
      believe by false feedback that they were experiencing either an increase or
      decrease in arousal, or evaluating the comfort level of the feedback equipment.
      Compared to the other groups, participants who believed their arousal had
      increased, reported greater anxiety, poorer perceived performance, more physical
      cues of anxiety, and greater underestimation of their performance and
      overestimation of the visibility of their anxiety. The effects were not specific
      to participants with high social anxiety. Observers rated the behaviour of
      participants who believed that their arousal had decreased most favourably. The
      results have implications for the treatment of social phobia.

PMID- 17223073
TI  - Role of the cytoskeleton in extracellular calcium-regulated PTH release.
AB  - The calcium-sensing receptor (CaR) mediates the effects of extracellular calcium
      ([Ca(2+)](o)) on PTH release, such that increasing levels of [Ca(2+)](o) inhibit
      PTH secretion through poorly defined mechanisms. In the present studies,
      immunocytochemical analysis demonstrated that F-actin, PTH, CaR, and caveolin-1
      are colocalized at the apical secretory pole of PT cells, and subcellular
      fractionation of PT cells showed these proteins to be present within the
      secretory granule fraction. High [Ca(2+)](o) caused F-actin, PTH, and caveolin-1
      to move to the apical pole of the cells. Depolymerization of F-actin by
      cytochalasin reduced the actin network and induced redistribution of
      actin/caveolin-1 to a dispersed pattern within the cell. The F-actin-severing
      compounds, latrunculin and cytochalasin, significantly increased PTH secretion,
      while the actin polymerizing agent, jasplakinolide, substantially inhibited PTH
      secretion. We have demonstrated that in polarized PT cells, the F-actin
      cytoskeleton is involved in the regulation of PTH secretion and is critical for
      inhibition of PTH secretion by high calcium.

PMID- 17223074
TI  - HAMLET, protein folding, and tumor cell death.

PMID- 17223075
TI  - Apoptin T108 phosphorylation is not required for its tumor-specific nuclear
      localization but partially affects its apoptotic activity.
AB  - Apoptin, a chicken anemia virus-encoded protein, induces apoptosis in human tumor
      cells but not in normal cells. In addition, Apoptin also exhibits tumor-specific
      nuclear localization and tumor-specific phosphorylation on threonine 108 (T108).
      Here, we studied the effects of T108 phosphorylation on the tumor-specific
      nuclear localization and apoptotic activity of Apoptin. We first showed that a
      hemagglutinin (HA)-tagged Apoptin, but not the green fluorescent protein-fused
      Apoptin used in many previous studies, exhibited the same intracellular
      distribution pattern as native Apoptin. We then made and analyzed an HA-Apoptin
      mutant with its T108 phosphorylation site abolished. We found that Apoptin T108
      phosphorylation is not required for its tumor-specific nuclear localization and
      abolishing the T108 phosphorylation of Apoptin does affect its apoptotic activity
      in tumor cells but only partially. Our results support the previous finding that
      Apoptin contains two distinct apoptosis domains located separately at the N- and
      C-terminal regions and suggest that the T108 phosphorylation may only be required
      for the apoptotic activity mediated through the C-terminal apoptosis domain.

PMID- 17223076
TI  - Exercise reduces adipose tissue via cannabinoid receptor type 1 which is
      regulated by peroxisome proliferator-activated receptor-delta.
AB  - Obesity is one major cardiovascular risk factor. We tested effects of endurance
      exercise on cannabinoid receptor type 1 (CB1) and peroxisome proliferator
      activated receptor-delta (PPAR-delta)-dependent pathways in adipose tissue. Male
      Wistar rats were randomly assigned to standard laboratory chow or a high-fat diet
      without and with regular endurance exercise. Exercise in rats on high-fat diet
      significantly reduced visceral fat mass, blood pressure, and adipocyte size (each
      p<0.05). Adipocyte hypertrophy induced by high-fat diet was accompanied by
      increased CB1 expression in adipose tissue, whereas exercise significantly
      reduced CB1 expression (each p<0.05). CB1 receptor expression and adipocyte
      differentiation were directly regulated by PPAR-delta. Adipocyte hypertrophy
      induced by high-fat diet was accompanied by reduced PPAR-delta. Furthermore,
      selective silencing of PPAR-delta by RNA interference in 3T3-L1-preadipocyte
      cells significantly increased CB1 expression from 1.00+/-0.06 (n=3) to 1.91+/
      0.06 (n=3; p<0.01) and increased adipocyte differentiation, whereas adenovirus
      mediated overexpression of PPAR-delta significantly reduced CB1 expression to
      0.39+/-0.03 (n=3; p<0.01) and reduced adipocyte differentiation. In the presence
      of the CB1 antagonist rimonabant adipocyte differentiation in stimulated 3T3 L1
      preadipocyte cells was significantly reduced. The study indicates that high-fat
      diet-induced hypertrophy of adipocytes is associated with increased CB1 receptor
      expression which is directly regulated by PPAR-delta. Both CB1 and PPAR-delta are
      intimately involved in therapeutic interventions against a most important
      cardiovascular risk factor.

PMID- 17223077
TI  - The binding of FKBP23 to BiP modulates BiP's ATPase activity with its PPIase
      activity.
AB  - Peptidyl-prolyl cis-trans-isomerases (PPIases) are enzymes that can cis-trans
      isomerize a Xaa-Pro peptide bond. Three families of PPIases are known:
      cyclophilins, FKBPs, and parvulins. The physiological functions of the PPIases
      are only poorly understood. In previous work, we reported that the mouse FK506
      binding protein 23 (mFKBP23), which comprises an N-terminal PPIase domain and a C
      terminal domain with Ca(2+)-binding sites, binds to mBiP in the endoplasmic
      reticulum (ER) and this binding is affected by the Ca(2+) concentration. In this
      study, we demonstrate the ability of mFKBP23 to modulate the ATPase activity of
      BiP, and that the bound mFKBP23, but not the free mFKBP23, can suppress the
      ATPase activity of mBiP through its PPIase activity.

PMID- 17223078
TI  - Higher plants possess two different types of ATX1-like copper chaperones.
AB  - Copper (Cu) chaperones constitute a family of small Cu+-binding proteins required
      for Cu homeostasis in eukaryotes. The ATX1 family of Cu chaperones specifically
      delivers Cu to heavy metal P-type ATPases. The plant Arabidopsis thaliana
      expresses the ATX1-like Cu chaperone CCH, which exhibits a plant-specific carboxy
      terminal domain (CTD) with unique structural properties. We show that CCH
      homologues from other higher plants contain CTDs with structural properties
      similar to Arabidopsis CCH. Furthermore, we identify a new ATX1-like Cu chaperone
      in Arabidopsis, AtATX1, which functionally complements yeast atx1Delta and
      sod1Delta associated phenotypes, and localizes to the cytosol of Arabidopsis
      cells. Interestingly, AtATX1, but not full-length CCH, interacts in vivo with the
      Arabidopsis RAN1 Cu-transporting P-type ATPase by yeast two-hybrid. We propose
      that higher plants express two types of ATX1-like Cu chaperones: the ATX1-type
      with a predominant function in Cu delivery to P-type ATPases, and the CCH-type
      with additional CTD-mediated plant-specific functions.

PMID- 17223079
TI  - Cholesterol: Coupling between membrane microenvironment and ABC transporter
      activity.
AB  - Lipid composition of biological membranes is closely related to the function of
      the ATP-binding cassette (ABC) transporter P-Glycoprotein (Pgp). Herein, we
      studied how membrane physico-chemical properties affect Pgp-activity. We
      effectively modulated the cellular cholesterol content using methyl-beta
      cyclodextrin (MbetaCD) and MbetaCD-cholesterol-inclusion complex. Pgp was not
      liberated from the plasma membrane during cholesterol modulation and functional
      inhibition of Pgp was related to varying cholesterol levels in the plasma
      membrane. Our data indicate that membrane fluidity does not solely account for
      cholesterol dependent modifications of Pgp-activity. Therefore, we isolated lipid
      rafts and examined distinct membrane microdomains. Both depletion and cholesterol
      enrichment induces a disassembly of lipid rafts. In cholesterol-depleted cell
      membranes a shift in the Pgp localisation to detergent soluble fractions was
      observed. Enrichment of membrane cholesterol changed lipid raft distribution but
      not the localisation of Pgp. From our data we conclude that Pgp-transport
      capacity depends on accurate lipid raft properties.

PMID- 17223080
TI  - Bipartite nuclear localization signal of matrin 3 is essential for vertebrate
      cells.
AB  - Matrin 3, a nuclear matrix protein has potential (1) to withhold promiscuously
      edited RNAs within the nucleus in cooperation with p54(nrb) and PSF, (2) to
      mediate NMDA-induced neuronal death, and (3) to modulate promoter activity of
      genes proximal to matrix/scaffold attachment region (MAR/SAR). We identified a
      bipartite nuclear localization signal (NLS) of chicken matrin 3 (cmatr3) at
      residues 583-602. By expressing green fluorescent protein (GFP) fused to the NLS
      mutant in chicken DT40 cells, we showed an essential role of the NLS for cell
      proliferation. Furthermore, we showed that both clusters of basic amino acids and
      a linker of the bipartite NLS were essential and sufficient for the nuclear
      import of GFP. Exogenous cmatr3 rescued the HeLa cells where human matrin 3 was
      suppressed by RNA interference, but cmatr3 containing deletions at either of the
      basic amino acid clusters or the linker could not.

PMID- 17223081
TI  - Factors required for the catalytic reaction of PqqC/D which produces
      pyrroloquinoline quinone.
AB  - PqqC/D converts the biosynthetic intermediate purified from a pqqC mutant to
      pyrroloquinoline quinone (PQQ), and both NAD(P)H and cytosolic fraction, named as
      activating factor (ActF), are required to show its higher production.
      Dithiothreitol alone, as well as ActF plus NAD(P)H, enhanced the PQQ production
      by PqqC/D. Thioredoxin-thioredoxin reductase system with NADPH showed similar
      effect. PqqC/D made a tight complex with PQQ, however, in the presence of
      dithiothreitol, PQQ was dissociated from the protein. ActF showed NADPH oxidase
      activity which was enhanced by the addition of PQQ. These data suggest that
      PqqC/D produces the reduced PQQ from the intermediate in vivo, but in vitro, it
      is further oxidized by molecular oxygen and then the oxidized PQQ is trapped in
      PqqC/D to show product inhibition.

PMID- 17223082
TI  - Radiosensitization effect of zidovudine on human malignant glioma cells.
AB  - Telomeres are shortened with each cell division and play an important role in
      maintaining chromosomal integrity and function. Telomerase, responsible for
      telomere synthesis, is activated in 90% of human tumor cells but seldom in normal
      somatic cells. Zidovudine (AZT) is a reverse transcriptase inhibitor. In this
      study, we have investigated the effects of gamma-radiation in combination with
      AZT on telomerase activity (TA), telomere length, DNA single-strand breaks
      (SSBs), DNA double-strand breaks (DSBs), and the changes in radiosensitivity of
      human malignant glioma cell line U251. The results showed that the TA was
      suppressed by AZT but enhanced by irradiation, resulting in a deceleration of
      restored rate of shortened telomere, decreased repair rate of DNA strand breaks,
      and increased radiosensitivity of U251 cells. Our results suggested that
      telomerase activity and telomere length may serve as markers for estimating the
      efficacy of cancer radiotherapy and reverse transcriptase inhibitors, such as
      AZT, may be used clinically as a new radiosensitizer in cancer radiotherapy.

PMID- 17223083
TI  - Diclofenac hydroxylation in monkeys: efficiency, regioselectivity, and response
      to inhibitors.
AB  - The catalytic efficiency, regioselectivity, and response to chemical inhibitors
      of diclofenac (DF) hydroxylation in three Old World monkey liver microsomes
      (rhesus, cynomolgus, and African green monkey) are different from those
      determined with human liver microsomes. In contrast to the high affinity-high
      capacity (low Km-high Vmax) characteristics of DF 4'-hydroxylation in humans,
      this reaction proceeded in all monkey species with catalytic efficiencies >20
      fold lower. However, DF 5-hydroxylation, a negligible reaction in human liver
      microsomes, was kinetically favored in monkeys mainly due to the increased Vmax
      values. Chemical inhibitors (reversible or mechanism-based) selective to human
      CYP3A4 and CYP2C9 failed to differentiate monkey orthologs involved in DF
      hydroxylation. Immunoinhibition studies with monoclonal antibodies against human
      CYPs revealed the major contribution of CYP2C and CYP3A to 4'- and to 5
      hydroxylation, respectively, in rhesus and cynomolgus liver microsomes. However,
      in African green monkeys, in addition to CYP2C, CYP3A also appeared to be
      involved in 4'-hydroxylation. Further studies with recombinant rhesus and African
      green monkey CYP2C and CYP3A enzymes (rhesus CYP2C75, 2C74, and 3A64; African
      green monkey CYP2C9agm and CYP3A4agm) confirmed the major role of CYP enzymes of
      these two subfamilies in DF 4'- and 5-hydroxylation. Clearly, while monkey CYP2C
      and 3A enzymes retain the same substrate selectivity towards DF hydroxylation as
      their human orthologs, their altered catalytic efficiency and response to
      chemical inhibitors may indicate different structural features of active sites as
      opposed to human orthologs.

PMID- 17223084
TI  - Amino terminal domains of human UDP-glucuronosyltransferases (UGT) 2B7 and 2B15
      associated with substrate selectivity and autoactivation.
AB  - Despite the important role of UDP-glucuronosyltransferases (UGT) in the
      metabolism of drugs, environmental chemicals and endogenous compounds, the
      structural features of these enzymes responsible for substrate binding and
      selectivity remain poorly understood. Since UGT2B7 and UGT2B15 exhibit distinct,
      but overlapping, substrate selectivities, UGT2B7-UGT2B15 chimeras were
      constructed here to identify substrate binding domains. A UGT2B7-15-7 chimera
      that incorporated amino acids 61-194 of UGT2B15 glucuronidated the UGT2B15
      substrates testosterone and phenolphthalein, but not the UGT2B7 substrates
      zidovudine and 11alpha-hydroxyprogesterone. Derived apparent K(m) values for
      testosterone and phenolphthalein glucuronidation by UGT2B7-15((61-194))-7 were
      similar in magnitude to those determined for UGT2B15. Moreover, glucuronidation
      of the non-selective substrate 4-methylumbelliferone (4MU) by UGT2B7-15((61-194))
      7 and UGT2B15 followed Michaelis-Menten and weak substrate inhibition kinetics,
      respectively, whereas 4MU glucuronidation by UGT2B7 exhibited sigmoidal kinetics
      characteristic of autoactivation. Six UGT2B7-15-7 chimeras that incorporated
      smaller domains of UGT2B15 were subsequently generated. Of these, UGT2B7-15((61
      157))-7, UGT2B7-15((91-157))-7 and UGT2B7-15((61-91))-7 glucuronidated 4MU, but
      activity towards the other substrates investigated here was not detected. Like
      UGT2B7, the UGT2B7-15((61-157))-7, UGT2B7-15((91-157))-7 and UGT2B7-15((61-91))-7
      chimeras exhibited sigmoidal 4MU glucuronidation kinetics. The sigmoidal 4MU
      kinetic data were well modelled using both the Hill equation and the expression
      for a two-site model that assumes the simultaneous binding of two substrate
      molecules at equivalent sites. It may be concluded that residues 61-194 of
      UGT2B15 are responsible for substrate binding and for conferring the unique
      substrate selectivity of UGT2B15, while residues 158-194 of UGT2B7 appear to
      facilitate the binding of multiple 4MU molecules within the active site.

PMID- 17223085
TI  - CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial.
AB  - BACKGROUND: CYP2B6 is the primary enzyme involved in bupropion (Zyban;
      GlaxoSmithKline, Research Triangle Park, North Carolina) metabolism. Genetic
      polymorphisms in CYP2B6, such as CYP2B6*6, can alter bupropion metabolism and may
      affect bupropion treatment outcome. METHODS: Subjects participated in a smoking
      cessation clinical trial of bupropion versus placebo. The main outcome was a 7
      day point prevalence abstinence rate measured 10 weeks after the start of
      treatment (i.e., end of treatment) and at the 6-month follow-up; secondary
      outcomes were severity of adverse effects, withdrawal, and urge to smoke.
      Subjects were haplotyped for the CYP2B6*6 variants. RESULTS: Among smokers in the
      CYP2B6*6 group (CYP2B6*1/*6 or CYP2B6*6/*6 genotype, n = 147, 45% of the
      population), bupropion produced significantly higher abstinence rates than
      placebo at the end of treatment (32.5% vs. 14.3%, p = .01) and at the 6-month
      follow-up (31.2% vs. 12.9%, p = .008). In contrast, bupropion was no more
      effective than placebo for smokers in the CYP2B6*1 group (CYP2B6*1/*1, n = 179)
      at the end of treatment (31.0% vs. 31.6%, p = .93) or at the 6-month follow-up
      (22.0% vs. 21.5%, p = .94). There was a significant genotype by treatment
      interaction at the end of treatment (odds ratio [OR] = 2.97, confidence interval
      [CI] = 1.05-8.40, p = .04), which was similar at 6-month follow-up (OR = 2.98, CI
      = .98-9.06, p = .05). CONCLUSIONS: These data suggest that smokers with the
      CYP2B6*6 genotype have a higher liability to relapse on placebo and that they may
      be good candidates for bupropion treatment for smoking cessation.

PMID- 17223086
TI  - Seizure incidence in psychopharmacological clinical trials: an analysis of Food
      and Drug Administration (FDA) summary basis of approval reports.
AB  - BACKGROUND: Clinical trial data provide an approach to the investigation of the
      effects of psychopharmacological agents, and psychiatric disorders themselves, on
      seizure threshold. METHODS: We accessed public domain data from Food and Drug
      Administration (FDA) Phase II and III clinical trials as Summary Basis of
      Approval (SBA) reports that noted seizure incidence in trials of psychotropic
      drugs approved in the United States between 1985 and 2004, involving a total of
      75,873 patients. We compared seizure incidence among active drug and placebo
      groups in psychopharmacological clinical trials and the published rates of
      unprovoked seizures in the general population. RESULTS: Increased seizure
      incidence was observed with antipsychotics that was accounted for by clozapine
      and olanzapine, and with drugs indicated for the treatment of OCD that was
      accounted for by clomipramine. Alprazolam, bupropion immediate release (IR) form,
      and quetiapine were also associated with higher seizure incidence. The incidence
      of seizures was significantly lower among patients assigned to antidepressants
      compared to placebo (standardized incidence ratio = .48; 95% CI, .36- .61). In
      patients assigned to placebo, seizure incidence was greater than the published
      incidence of unprovoked seizures in community nonpatient samples. CONCLUSIONS:
      Proconvulsant effects are associated with a subgroup of psychotropic drugs.
      Second-generation antidepressants other than bupropion have an apparent
      anticonvulsant effect. Depression, psychotic disorders, and OCD are associated
      with reduced seizure threshold.

PMID- 17223087
TI  - Neuron death and inflammation in a rat model of intracerebral hemorrhage: effects
      of delayed minocycline treatment.
AB  - After intracerebral hemorrhage (ICH), blood entry is followed by neuron death and
      an inflammatory response, but development of pharmacological therapies has been
      hampered by an inadequate understanding of the spatial and temporal relationship
      between neuron death and inflammation. Using a rat model of ICH, we first
      investigated these relationships at 6 h, and 1, 3 and 7 days. At the edge of the
      hematoma, no degenerating neurons were observed at 6 h; however, dying neurons
      were present between 1 and 3 days, with peak neuron death occurring at 1 day.
      This is apparently the first report of ongoing neuron death at the edge of the
      hematoma during a time window that is appropriate for human therapy. Neuron death
      was limited to the edge of the hematoma, with no degenerating neurons in the
      striatum surrounding the hematoma, despite robust and prolonged microglia
      activation. Importantly, neuron loss at the edge of the hematoma was spatially
      and temporally associated with accumulation and activation of
      microglia/macrophages. We then tested the hypothesis that treatment with the
      tetracycline derivative, minocycline, after the hematoma had reached a maximal
      size, will reduce inflammation and neuron damage. Minocycline injection (45 mg/kg
      i.v. at 6 h, and i.p. at 24, 48 and 72 h) failed to reduce neuron loss outside
      the hematoma or striatal tissue loss (assessed at 7 days), despite reducing the
      number of neutrophils and activated microglia/macrophages. Thus, minocycline does
      not appear to target the mechanisms responsible for cell death in this model of
      ICH.

PMID- 17223088
TI  - Creatine promotes the GABAergic phenotype in human fetal spinal cord cultures.
AB  - In the present study, we investigated the expression pattern of cytosolic brain
      specific-BB-CK and ubiquitous mitochondrial-creatine kinases (uMt-CK) in
      developing human spinal cord. Consequently, we studied the effects of creatine
      treatment on cultured fetal human spinal cord tissue. We found that both CK
      isoforms were expressed in fetal spinal cord at all time points investigated (5
      to 11.5 weeks post conception) and correspondingly specific CK activity was
      detected. Chronic creatine exposure resulted in significantly higher densities of
      GABA-immunoreactive neurons in the cultures, while total neuronal cell density
      was not altered, suggesting a differentiation inducing mechanism of creatine
      supplementation. Taken together, our observations favour the view that the
      creatine phosphocreatine system plays an important role in the developing CNS.

PMID- 17223089
TI  - Enzymatic properties and localization of motopsin (PRSS12), a protease whose
      absence causes mental retardation.
AB  - Motopsin (PRSS12) is a mosaic protease expressed in the central nervous system.
      Truncation of the human motopsin gene causes nonsyndromic mental retardation.
      Understanding the enzymatic properties and localization of motopsin protein in
      the central nervous system will help identify the molecular mechanism by which
      the loss of motopsin function causes mental retardation. Recombinant motopsin
      showed amidolytic activity against the synthetic substrate benzyloxycarbonyl-l
      phenylalanyl-l-arginine 4-methyl-coumaryl-7-amide. Motopsin activated the single
      chain tissue plasminogen activator precursor and exhibited gelatinolytic
      activity. This enzymatic activity was inhibited by typical serine protease
      inhibitors such as aprotinin, leupeptin, and (4-amidinophenyl) methanesulfonyl
      fluoride. Immunocytochemistry using anti-motopsin IgG revealed that both human
      and mouse motopsin proteins were distributed in discrete puncta along the
      dendrites and soma as well as axons in cultured hippocampal neurons. In the
      limbic system, including the cingulate and hippocampal pyramidal neurons and
      piriform cortex, high level of motopsin protein was expressed at postnatal day
      10, but a very low level at 10-week-old mice. Motopsin and tissue plasminogen
      activator were co-expressed in the cingulate pyramidal neurons at postnatal day
      10 and were distributed along dendrites of cultured pyramidal neurons. In cranial
      nuclei, a moderate level of motopsin protein was detected independently on the
      developmental stage. Our results suggest that motopsin has multiple functions,
      such as axon outgrowth, arranging perineuronal environment, and maintaining
      neuronal plasticity, partly in coordination with other proteases including tissue
      plasminogen activator.

PMID- 17223090
TI  - Lesions to the nucleus basalis magnocellularis lower performance but do not block
      the retention of a previously acquired learning set.
AB  - Rats were first trained to acquire an olfactory discrimination learning set
      (ODLS) on 40 olfactory-unique discrimination problems. Following acquisition of
      ODLS, animals were lesioned bilaterally in the nucleus basalis magnocellularis
      (nBM) using either quisqualic acid (QUIS) or 192 IgG-saporin (SAP). QUIS animals
      performed significantly worse than control animals following surgery and SAP
      animals performed transiently worse than control animals. Despite lowered
      performances, both QUIS and SAP animals performed significantly better than
      expected by chance on trial 2 indicating retention of the ODLS previously
      acquired. Implications for the role of the nBM in aspects of cognitive
      flexibility and its role in acquisition versus retention are discussed.

PMID- 17223091
TI  - Selection and maintenance of stimulus-response rules during preparation and
      performance of a spatial choice-reaction task.
AB  - The ability to select an appropriate response among competing alternatives is a
      fundamental requirement for successful performance of a variety of everyday
      tasks. Recent research suggests that a frontal-parietal network of brain regions
      (including dorsal prefrontal, dorsal premotor and superior parietal cortices)
      mediate response selection for spatial material. Most of this research has used
      blocked experimental designs. Thus, the frontal-parietal activity reported may be
      due either to tonic activity across a block or to processing occurring at the
      trial level. Our current event-related fMRI study investigated response selection
      at the level of the trial in order to identify possible response selection sub
      processes. In the study, participants responded to a visually presented stimulus
      with either a spatially compatible or incompatible manual response. On some
      trials, several seconds prior to stimulus onset, a cue indicated which task was
      to be performed. In this way we could identify separate brain regions for task
      preparation and task performance, if they exist. Our results showed that the
      frontal-parietal network for spatial response selection activated both during
      task preparation as well as during task performance. We found no evidence for
      preparation specific brain mechanisms in this task. These data suggest that
      spatial response selection and response preparation processes rely on the same
      neurocognitive mechanisms.

PMID- 17223092
TI  - Perceptual and cognitive task difficulty has differential effects on auditory
      distraction.
AB  - When a task-irrelevant feature of an auditory stimulus varies at rare and
      unpredictable times, the processing of this change interferes with the processing
      of task-relevant stimulus information. The present study investigated whether
      this distraction effect is modulated by the difficulty of the auditory task.
      Event-related potentials (ERPs) and behavioral responses were recorded while
      subjects classified stimuli based on their temporal dimension. In one condition,
      the task was made more difficult by decreasing the perceptual discriminability
      (temporal distinctiveness) of the stimuli. In a second condition, the difficult
      task involved an increase in memory load: subjects were asked to assess the
      duration of the current compared to that of the previous stimulus. The occurrence
      of an infrequent task-irrelevant change in the pitch of the stimulus caused
      distraction in all task conditions. Following this change, performance
      deteriorated, and a distinct P3a component was visible in the ERP. Importantly,
      the extent of this distraction effect was significantly enhanced during the high
      memory load task, but not during the difficult perceptual task. It may be that
      the attentional resources afforded to the stimuli, rather than task difficulty,
      affected the extent of the distraction response. When the processing requirements
      of a task demand more highly focused attention for stimulus processing, the
      processing of the distracting information embedded within this stimulus may
      inadvertently also benefit from this attention.

PMID- 17223093
TI  - Neurons expressing serotonin-1B receptor in the basolateral nuclear group of the
      amygdala in normally behaving and aggressive dogs.
AB  - The present study aimed to quantify neurons expressing the serotonin-1B receptor
      and evaluate numerical differences in normally behaving and pathologically
      aggressive dogs in order to assess whether the serotonin-1B receptor is involved
      in pathological canine aggression. Because previous studies have reported
      structural alterations in the basolateral nuclear group (BNG) of the amygdaloid
      body of aggressive dogs, this structure was selected as region of interest in the
      present study. Indirect immunohistochemistry was applied to visualise the
      serotonin-1B-receptor-positive neurons. Immunoreactivity was located
      predominantly within the neuronal cell bodies and adjacent neuronal processes. In
      the aggressive dogs the BNGs contained a significantly higher number of serotonin
      1B-receptor-positive neurons compared to the normally behaving dogs. This number
      was strongly correlated with the total number of neurons per BNG, which was also
      significantly increased in aggressive dogs compared to normal dogs. The
      percentage of neurons expressing the serotonin-1B receptor did not differ
      significantly between both groups. No significant asymmetries were observed for
      the number and percentage of serotonin-1B-receptor-positive neurons. Potential
      relationships between the present findings and the etiology of aggressive
      behaviour, the neuroprotective role of the serotonin-1B receptor and receptor
      dysfunction are discussed.

PMID- 17223094
TI  - A short alternative preparation of the bengazoles polyol side-chain segment.
AB  - A new short and efficient synthesis of the bengazoles side chain is reported
      using a sequential Grignard addition-hydroboration approach on a readily
      available d-ribose derivative.

PMID- 17223095
TI  - Serum lipoprotein lipase mass: clinical significance of its measurement.
AB  - Lipoprotein lipase (LPL) is a lipolytic enzyme involved in catalyzing hydrolysis
      of triglycerides (TG) in chylomicrons and very low-density lipoprotein (VLDL)
      particles. Over the last decade, increasing attention has been paid to the
      clinical significance of measuring serum LPL protein mass without heparin
      injection to the study subjects. In earlier studies, this marker was utilized to
      classify LPL deficient subjects, which is an extremely rare metabolic disorder
      with a frequency of one in one million. Later, researchers paid more attention to
      the clinical significance of measuring this parameter in more common metabolic
      disorders. Studies have shown that pre-heparin plasma or serum LPL mass has
      significant relationships with serum lipids and lipoproteins, visceral fat area,
      insulin resistance, and even the development of coronary atherosclerosis in cross
      sectional studies, although this might be a metabolic surrogate marker with
      almost no catalytic activities, which does not appear to be involved in
      catalyzing hydrolysis of TG in TG-rich lipoproteins. Recently, a prospective
      study has demonstrated that low serum LPL concentration predicts future coronary
      events. Taken together, we suggest that pre-heparin LPL mass in plasma or sera
      provide us with useful and important information on the development of metabolic
      disorders leading to atherosclerotic disease.

PMID- 17223096
TI  - Rule following and rule use in the balance-scale task.
AB  - Quinlan et al. [Quinlan, p., van der Mass, H., Jansen, B., Booij, O., & Rendell,
      M. (this issue). Re-thinking stages of cognitive development: An appraisal of
      connectionist models of the balance scale task. Cognition,
      doi:10.1016/j.cognition.2006.02.004] use Latent Class Analysis (LCA) to criticize
      a connectionist model of development on the balance-scale task, arguing that LCA
      shows that this model fails to capture a torque rule and exhibits rules that
      children do not. In this rejoinder we focus on the latter problem, noting the
      tendency of LCA to find small, unreliable, and difficult-to-interpret classes.
      This tendency is documented in network and synthetic simulations and in
      psychological research, and statistical reasons for finding such unreliable
      classes are discussed. We recommend that LCA should be used with care, and argue
      that its small and unreliable classes should be discounted. Further, we note that
      a preoccupation with diagnosing rules ignores important phenomena that rules do
      not account for. Finally, we conjecture that simple extensions of the network
      model should be able to achieve torque-rule performance.

PMID- 17223097
TI  - Similarity and attraction effects in episodic memory judgments.
AB  - In the decision-making literature, it is known that preferences between two
      options can be influenced in different ways by the introduction of a third
      option. We investigated whether such influences could be demonstrated when making
      decisions about qualitative aspects of episodic memories. In a baseline
      condition, participants were asked which of two dissimilar events they remembered
      more vividly: (A) a well-known Olympic victory, or (B) the death of a well-known
      public figure. In two further conditions, a third event was added: (C) an Olympic
      victory similar and competitive to A, or (D) an Olympic victory similar but
      inferior to A. With the addition of C, participants were less likely to choose A
      than B (similarity effect), whereas with the addition of D, they were more likely
      to choose A than B (attraction effect), suggesting that effects known in decision
      making can be generalised to relative judgments about episodic memories.

PMID- 17223098
TI  - Ephrin-B2 forward signaling regulates somite patterning and neural crest cell
      development.
AB  - Genetic studies in the mouse have implicated ephrin-B2 (encoded by the gene
      Efnb2) in blood vessel formation, cardiac development and remodeling of the
      lymphatic vasculature. Here we report that loss of ephrin-B2 leads to defects in
      populations of cranial and trunk neural crest cells (NCC) and to defective somite
      development. In addition, we show that Efnb1/Efnb2 double heterozygous embryos
      exhibit phenotypes in a number of NCC derivatives. Expression of one copy of a
      mutant version of Efnb2 that lacks tyrosine phosphorylation sites was sufficient
      to rescue the embryonic phenotypes associated with loss of Efnb2. Our results
      uncover an important role for ephrin-B2 in NCC and somites during embryogenesis
      and suggest that ephrin-B2 exerts many of its embryonic function via activation
      of forward signaling.

PMID- 17223099
TI  - Spatio-temporal expression of Prospero is finely tuned to allow the correct
      development and function of the nervous system in Drosophila melanogaster.
AB  - Adaptive animal behaviors depend upon the precise development of the nervous
      system that underlies them. In Drosophila melanogaster, the pan-neural prospero
      gene (pros), is involved in various aspects of neurogenesis including cell cycle
      control, axonal outgrowth, neuronal and glial cell differentiation. As these
      results have been generally obtained with null pros mutants inducing embryonic
      lethality, the role of pros during later development remains poorly known. Using
      several pros-Voila (prosV) alleles, that induce multiple developmental and
      behavioral anomalies in the larva and in adult, we explored the relationship
      between these phenotypes and the variation of pros expression in 5 different
      neural regions during pre-imaginal development. We found that the quantity of
      pros mRNA spliced variants and of Pros protein varied between these alleles in a
      tissue-specific and developmental way. Moreover, in prosV1 and prosV13 alleles,
      the respective decrease or increase of pros expression, affected (i) neuronal and
      glial cell composition, (ii) cell proliferation and death and (iii) axonal
      dendritic outgrowth in a stage and cellular context dependant way. The various
      phenotypic consequences induced during development, related to more or less
      subtle differences in gene expression, indicate that Pros level needs a precise
      and specific adjustment in each neural organ to allow its proper function.

PMID- 17223100
TI  - Tissue-specific laminin expression facilitates integrin-dependent association of
      the embryonic wing disc with the trachea in Drosophila.
AB  - The interaction of heterologous tissues involves cell adhesion mediated by the
      extracellular matrix and its receptor integrins. The Drosophila wing disc is an
      ectodermal invagination that contacts specific tracheal branches at the
      basolateral cell surface. We show that an alpha subunit of laminin, encoded by
      wing blister (wb), is essential for the establishment of the interaction between
      the wing and trachea. During embryogenesis, wing disc cells present Wb at their
      basolateral surface and extend posteriorly, expanding their association to more
      posteriorly located tracheal branches. These migratory processes are impaired in
      the absence of the trachea, Wb, or integrins. Time-lapse and transmission
      electron microscopy analyses suggest that Wb facilitates integrin-dependent
      contact over a large surface and controls the cellular behavior of the wing
      cells, including their exploratory filopodial activity. Our data identify Wb
      laminin as an extracellular matrix ligand that is essential for integrin
      dependent cellular migration in Drosophila.

PMID- 17223101
TI  - The effects of non-medically used psychoactive drugs on monoamine
      neurotransmission in rat brain.
AB  - We developed a reproducible, simple, and small-scale method for determining the
      re-uptake and release of monoamines (dopamine, serotonin (5-HT) and
      norepinephrine) using rat brain synaptosomes. These assays were then applied to
      study the effects of different kinds of non-medically used psychoactive drugs on
      monoamine re-uptake and release. The phenethylamine derivatives, 4
      fluoroamphetamine, 2-methylamino-3,4-methylene-dioxy-propiophenone (methylone), 1
      (1,3-benzodioxol-5-yl)-2-butanamine (BDB), and N-methyl-1-(1,3-benzodioxol-5-yl)
      2-butanamine (MBDB), had strong inhibitory effects on the re-uptake of dopamine,
      5-HT and norepinephrine. 4-Fluoroamphetamine, methylone and BDB also strongly
      increased the release of the three monoamines, but MBDB increased 5-HT and
      norepinephrine release, but had little effect on dopamine release. However, 2,5
      dimethoxy-4-iodophenethylamine (2C-I), 2,5-dimethoxy-4-ethylphenethylamine (2C
      E), 2,5-dimethoxy-4-chlorophenethylamine (2C-C), 2,4,5-trimethoxyamphetamine (TMA
      2) and 2,4,6-trimethoxyamphetamine (TMA-6), which are methoxylated phenethylamine
      derivatives, slightly influenced the re-uptake and release of monoamines. Alpha
      metyltryptamine (AMT), a tryptamine derivative, was one of the strongest re
      uptake inhibitors and releasers of the three monoamines. The tryptamine
      derivative, 5-methoxy-alpha-methyltryptamine (5-MeO-AMT), also strongly inhibited
      re-uptake and increased the release of the three monoamines. N,N
      dipropyltryptamine (DPT), 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), 5
      methoxy-N,N-methylisopropyltryptamine (5-MeO-MIPT), and 5-methoxy-N,N
      dimethyltryptamine (5-MeO-DMT) inhibited monoamine re-uptake, but had a few
      effects on monoamine release. 1-(3-Chlorophenyl)piperazine (3CPP) and 1
      (methoxyphenyl)piperazine (4MPP), which are piperazine derivatives, inhibited
      monoamine re-uptake and accelerated their release. The results suggest that some
      designer drugs strongly act on the central nerve system to the same extent as
      restricted drugs.

PMID- 17223102
TI  - 2-(3-Fluorophenyl)-6-methoxyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (YJC
      1) induces mitotic phase arrest in A549 cells.
AB  - A 2-phenyl-4-quinolone (2-PQ) derivative, 2-(3-fluorophenyl)-6-methoxyl-4-oxo-1,4
      dihydroquinoline-3-carboxylic acid (YJC-1), was synthesized in our laboratory. In
      this study, we delineated the growth-inhibitory effect of YJC-1 in human lung
      carcinoma A549 cells. YJC-1 inhibited cell growth with an IC(50) value of about
      4.8 microM via microtubule polymerization, causing growth arrest in the mitotic
      phase. Immunoblotting analysis revealed a dramatic induction of cyclin-dependent
      kinase (CDK) inhibitor p21(Cip1/Waf1) and down-regulation of Cdc25C phosphatase
      to inhibit the protein expression of cyclin B1 and CDK1. We also found that YJC-1
      induced a profound time-dependent elevation in p21(Cip1/Waf1) gene expression in
      comparison with the negative control. In vivo, we also found that YJC-1
      significantly suppressed tumor growth in mice inoculated with A549 cells. These
      findings suggest that YJC-1 can suppress A549 cell growth via mitotic phase
      arrest.

PMID- 17223104
TI  - Establishment of a corneal epithelial cell line spontaneously derived from human
      limbal cells.
AB  - The objective of this study was to establish a spontaneously derived human
      corneal epithelial cell line from a normal human limbus that retains
      differentiation potential and proliferative properties under continuous cell
      culture. After 50 passages of epithelial cells obtained from human limbal tissue
      a cell line spontaneously emerged. The immortalized cells showed a cobblestone
      appearance and displayed dense microvilli on their apical cell surface membrane.
      Colony forming efficiency was 5-6% and population doubling time was 19.6 h. In
      the mRNA level, cytokeratin (CK) 3 and 12 were detected in this cell line. In the
      protein level, the cells expressed CK3, CK12, CK14, CK19, vimentin, and some
      other proteins such as F-actin and beta-tubulin and beta(1)-integrin. They lacked
      p63. The immortalized cells had a heteroploid karyotype, but did not exhibit
      tumorigenic features. When cultured on an air-liquid interface the cells could
      form stratified multilayer epithelia. In summary, all these results indicated
      that a new human corneal epithelial cell line was spontaneously established from
      normal limbal tissue through serial culture. This cell line would be useful for
      studies of corneal epithelial biology and reconstructive corneal tissue
      engineering.

PMID- 17223103
TI  - Structural and functional analysis of the sarcoglycan-sarcospan subcomplex.
AB  - Sarcospan is a component of the dystrophin-glycoprotein complex that forms a
      tight subcomplex with the sarcoglycans. The sarcoglycan-sarcospan subcomplex
      functions to stabilize alpha-dystroglycan at the plasma membrane and
      perturbations of this subcomplex are associated with autosomal recessive limb
      girdle muscular dystrophy. In order to characterize protein interactions within
      this subcomplex, we first demonstrate that sarcospan forms homo-oligomers within
      the membrane. Experiments with a panel of site-directed mutants reveal that
      proper structure of the large extracellular loop is an important determinant of
      oligo formation. Furthermore, the intracellular N- and C-termini contribute to
      stability of sarcospan-mediated webs. Point mutation of each cysteine residue
      reveals that Cys 162 and Cys 164 within the large extracellular loop form
      disulfide bridges, which are critical for proper sarcospan structure. The
      extracellular domain of sarcospan also forms the main binding site for the
      sarcoglycans. We propose a model whereby sarcospan forms homo-oligomers that
      cluster the components of the dystrophin-glycoprotein complex within the
      membrane.

PMID- 17223105
TI  - Preventive and therapeutic anti-inflammatory effects of systemic and topical
      thalidomide on endotoxin-induced uveitis in rats.
AB  - The present study examined the outcomes of systemic or topical treatment with
      thalidomide, a compound that possesses anti-inflammatory, immunomodulatory and
      anti-angiogenic properties, in rats subjected to endotoxin-induced uveitis (EIU).
      The effects of thalidomide were evaluated on endotoxin-induced leucocyte and
      protein infiltration and also on the production of interleukin (IL)-1beta and
      tumour necrosis factor (TNF)-alpha in rat aqueous humour (AqH). Moreover, the
      actions of thalidomide were assessed on the cyclooxygenase (COX)-2 and inducible
      nitric oxide synthase (iNOS) protein expression in retinal tissue. EIU was
      produced by a hindpaw injection of lipopolysaccharide (LPS), in male Wistar rats.
      Thalidomide (5, 25 and 50 mg/kg) was administered orally 1 h before LPS
      injection. In another set of experiments, to evaluate the therapeutic efficacy,
      5% thalidomide was applied topically to both eyes at 6, 12 and 18 h after LPS
      administration. The oral pre-treatment with thalidomide decreased, in a dose
      dependent manner, the number of inflammatory cells, the protein concentration,
      and the levels of IL-1beta and TNF-alpha in the AqH. Similar results were found
      in the AqH of rats that received a topical application of thalidomide.
      Furthermore, oral (50 mg/kg) and local (5%) thalidomide treatment also reduced
      expression of the pro-inflammatory proteins COX-2 and iNOS in the posterior
      segment of the eye. Thalidomide exhibited marked preventive and curative ocular
      effects in EIU in rats, a property that might be associated with its ability to
      inhibit the production of inflammatory cytokines and the expression of COX-2 and
      iNOS. This assembly of data provides additional molecular and functional insights
      into beneficial effects of thalidomide as an agent for the management of ocular
      inflammation.

PMID- 17223106
TI  - Controlled delivery of glial cell line-derived neurotrophic factor by a single
      tetracycline-inducible AAV vector.
AB  - An autoregulated tetracycline-inducible recombinant adeno-associated viral vector
      (rAAV-pTet(bidi)ON) utilizing the rtTAM2 reverse tetracycline transactivator
      (rAAV-rtTAM2) was used to conditionally express the human GDNF cDNA. Doxycycline,
      a tetracycline analog, induced a time- and dose-dependent release of GDNF in
      vitro in human glioma cells infected with rAAV-rtTAM2 serotype 2 virus.
      Introducing the Woodchuck hepatitis virus posttranscriptional regulatory element
      (WPRE) downstream to the rtTAM2 coding sequence, resulted in a more rapid
      induction and a higher basal expression level. In vivo, 8 weeks after a single
      injection of the rAAV-rtTAM2-GDNF vector encapsidated into AAV serotype 1 capsids
      in the rat striatum, the GDNF protein level was 60 pg/mg tissue in doxycycline
      treated animals whereas in untreated animals, it was undistinguishable from the
      endogenous level ( approximately 4 pg/mg tissue). However, a residual GDNF
      expression in the uninduced animals was evidenced by a sensitive
      immunohistochemical staining. As compared to rAAV1-rtTAM2-GDNF, the rAAV1-rtTAM2
      WPRE-GDNF vector expressed a similar concentration of GDNF in the induced state
      (with doxycycline) but a basal level (without doxycycline) approximately 2.5-fold
      higher than the endogenous striatal level. As a proof for biological activity,
      for both vectors, downregulation of tyrosine hydroxylase was evidenced in
      dopaminergic terminals of doxycycline-treated but not untreated animals. In
      conclusion, the rAAV1-rtTAM2 vector which expressed biologically relevant doses
      of GDNF in the striatum in response to doxycycline with a basal level
      undistinguishable from the endogenous striatal level, as measured by quantitative
      ELISA assay, constitutes an interesting tool for local conditional transgenesis.

PMID- 17223107
TI  - Protection of mice against homologous or heterologous infections with antiserum
      mixture to the predominant variable antigen type repertoire of Trypanosoma evansi
      YNB stock.
AB  - The objective of this study was to test a hypothesis that the predominant
      variable antigen type (VAT) repertoire of a single stock of Trypanosoma evansi
      was limited and small. It was further assumed that six rabbits could produce all
      antibodies against the predominant VAT repertoire of a stock of T. evansi and the
      antiserum mixture from the six rabbits containing all the antibodies could
      completely protect mice against any homologous stock infections and partially
      protect mice against some heterologous stock infections. Mice were each
      intraperitoneally infected with 100 parasites of clone-derived and non-clone
      derived populations of the YNB stock, Kazakhstan strain or Vietnam strain of T.
      evansi, and treated with the antiserum mixture when trypanosomes had been
      detected in the blood. All of the 10 mice infected with either non-clone-derived
      or clone-derived populations of the YNB stock survived, and some (4/10) of mice
      infected with the heterologous Kazakhstan strain survived, while all those
      (10/10) infected with the heterologous Vietnam strain died. These results support
      the hypothesis that the predominant VAT repertoire of a single stock of T. evansi
      was limited and small, and have important implications in the consideration of
      treating human trypanosomosis due to drug resistant strains with antiserum
      mixture.

PMID- 17223109
TI  - Comparative genomic analysis of the mouse and rat amylase multigene family.
AB  - The rat and mouse amylase gene families were characterized using sequence data
      from the UCSC genome assembly. We found that the rat genome contains one amylase
      1 and two amylase-2 genes, lying close to one another on the same chromosome.
      Detailed analysis revealed at least six additional amylase pseudogenes in the rat
      genome in the region adjacent to the amylase-2 genes. In contrast, the mouse has
      one amylase-1 gene and five amylase-2 genes; the latter are tandemly and
      systematically arranged on the same chromosome and were generated by segmental
      duplication. Detailed analysis revealed that the mouse has two amylase
      pseudogenes, located 5' to the five amylase-2 segments. Thus, the amylase genes
      of mouse and rat tend to be amplified; the sequences of some of them are fixed
      while others have become pseudogenes during evolution. This is the second report
      of amylase genomic organization in mammals and the first in the rodents.

PMID- 17223110
TI  - Molecular cloning, tissue distribution, and developmental expression of lamprey
      transthyretins.
AB  - We isolated and cloned full-length cDNAs of transthyretin (TTR) from 2 genera of
      lamprey, Petromyzon marinus and Lampetra appendix. These sequences represent the
      first report of TTR sequences in vertebrates basal to teleost fishes. The deduced
      amino acid sequence of lamprey TTR cDNAs showed 36-47% identity with those from
      other vertebrates; secondary structure predictions and homology-based modeling
      were both consistent with TTRs from other vertebrates, and these cDNAs lacked the
      signatures found in TTR-like sequences of non-vertebrates. Of evolutionary
      interest is the observation that the N-termini of the lamprey TTR subunits are
      nine amino acids longer than those of eutherian TTRs and four to six amino acids
      longer than those from all other vertebrates. Sequencing of intron 1 confirmed
      that this longer N-terminal region is a result of the position of the intron
      1/exon 2 splice site, further supporting previous studies. TTR mRNA was detected
      in a variety of larval lamprey tissues, with the highest levels found in the
      liver. TTR mRNA was also readily detected by Northern blotting, in the livers of
      animals at all phases of the lifecycle and was significantly elevated during
      metamorphosis. The upregulation of lamprey TTR gene expression during a major
      developmental event is consistent with observations in other vertebrates. In all
      other vertebrates studied to date, the transient upregulation of TTR gene
      expression or some other thyroid hormone distributor protein coincides with, and
      is thought to facilitate, the surge in serum thyroid hormone concentrations
      required for normal development. However, in lampreys, the upregulation of TTR
      gene expression occurs when serum thyroid hormone concentrations are at their
      lowest.

PMID- 17223111
TI  - Outcomes of variation in hospital nurse staffing in English hospitals.

PMID- 17223112
TI  - Effect of rosuvastatin 5-20mg on triglycerides and other lipid parameters in
      Japanese patients with hypertriglyceridemia.
AB  - To evaluate the potential dose effect of rosuvastatin on triglyceride (TG) levels
      in Japanese hypertriglyceridemic patients, we randomized 154 patients with TG
      levels of >or=200 and <800 mg/dL to 8 weeks of treatment with rosuvastatin 5, 10
      or 20mg once daily; bezafibrate 200mg twice daily; or placebo. Compared with
      placebo, TG was reduced by 30.1% with rosuvastatin 5mg, 30.1% with 10mg and 32.3%
      with 20mg (all p<or=0.0001), with no evidence of a dose effect. Changes in TG
      were evident after 2 weeks of treatment and maintained thereafter. In a benchmark
      comparison, rosuvastatin across its dose range reduced TG by 29.1-31.1% from
      baseline versus 45.4% for bezafibrate. Compared with bezafibrate, rosuvastatin
      was superior with respect to changes in non-high-density lipoprotein cholesterol
      (non-HDL-C, -36.8 to -44.3% for rosuvastatin versus -2.0% for bezafibrate), low
      density lipoprotein cholesterol (-31.9 to -41.0% versus +29.3%), total
      cholesterol (-27.1 to -33.3% versus +2.1%), although smaller improvements in HDL
      C (12.4-16.7% versus 19.6%) were observed. Rosuvastatin also produced superior
      dose-related decreases in median high-sensitivity C-reactive protein (22.9
      38.5%). Treatment was well tolerated in both rosuvastatin and bezafibrate
      patients, with clinically important increases in alanine aminotransferase being
      rare, no adverse effect on renal function being observed and no cases of myopathy
      or rhabdomyolysis being reported. The current study does not suggest a dose
      related effect of rosuvastatin in lowering TG in hypertriglyceridemic Japanese
      patients, although dose-related improvements in other elements of the atherogenic
      lipid profile were observed.

PMID- 17223113
TI  - Influence of substituents on selectivity and efficiency of chiral separations of
      anions containing single nido-7,8-dicarbaundecaborane cluster with alpha
      cyclodextrin.
AB  - In background electrolyte (BGE) with the optimal methanol concentration of 30%
      (v/v), the ion with -NCS group bonded to a cluster boron atom exhibits the
      strongest interaction with alpha-cyclodextrin and the highest separation
      selectivity. Interaction of ions with alkyl or thioalkyl group weakens with the
      increasing substituent size. The ion with phenyl group exhibits the weakest
      interaction. Bonding of a group to boron atom weakens the ion interaction with
      alpha-cyclodextrin. Second substituent further weakens the interaction with alpha
      cyclodextrin. Separation efficiency is lower at the presence of alpha
      cyclodextrin than at its absence. This separation efficiency loss, amounts up to
      90%.

PMID- 17223114
TI  - Comprehensive analysis of branched aliphatic D-amino acids in mammals using an
      integrated multi-loop two-dimensional column-switching high-performance liquid
      chromatographic system combining reversed-phase and enantioselective columns.
AB  - A validated two-dimensional HPLC method for the comprehensive analysis of small
      quantities of branched aliphatic D-amino acids in the presence of large amounts
      of their L-congeners in mammalian tissues and physiological fluids is described.
      The quantitative analysis of these aliphatic amino acids (Val, allo-Ile, Ile, and
      Leu) is important for the diagnosis of various inherent metabolic disorders of
      amino acids, and the D-enantiomers are expected to be of particular interest from
      a pharmacological point of view. Target analytes were determined as their
      fluorescent derivatives, pre-column labeled with 4-fluoro-7-nitro-2,1,3
      benzoxadiazole (NBD-F), using an automated two-dimensional column-switching high
      performance liquid chromatographic system combining a narrow bore reversed-phase
      column and an enantioselective column connected with an integrated multi-loop
      peak fraction storage device. The described two-dimensional analysis concept
      proved to be successful for the given task in biological samples taken from
      mammals. Total analysis time for the reversed-phase separation of the four target
      NBD-amino acids is 60 min, and the integrated enantiomer separation of each of
      the four analytes is completed in approximately 5 min. In the rat, significant
      amounts of D-Leu were found in all tissues and physiological fluids tested (trace
      1.3 nmol/g tissue), and in the urine, the presence of high amounts of D-allo-Ile
      (D-isomer of a non-proteinogenic amino acid, 22.2 nmol/ml) was demonstrated. D
      allo-Ile was also found in the urine of dog and mouse, which indicates the
      ubiquitous presence of this unusual D-amino acid and the potential need to
      clarify its unique metabolism in mammals.

PMID- 17223115
TI  - New coupling of planar chromatography with direct analysis in real time mass
      spectrometry.
AB  - The coupling of planar chromatography with direct analysis in real time time-of
      flight mass spectrometry (DART-TOF-MS) was shown for the first time. Cutting the
      plate within a track led to substance zones positioned on the plate edge which
      were directly introduced into the DART gas stream. Mass signals were obtained
      instantaneously within seconds. Detectability was shown in the very low ng-range
      per zone on the example of isopropylthioxanthone. The coupling was perfectly
      suited for identification and qualitative purposes, but it was initially critical
      for quantification of results. Analytical response (R2 0.8202) and repeatability
      were strongly dependent from proper manual positioning of the HPTLC plate into
      the electronic or vibronic excited-state gas stream of the ion source. This
      drawback was overcome by using stable isotope-labeled standards shown on the
      example of caffeine. This way, analytical response (R2 0.9892) and repeatability
      (RSD < +/- 5.4%, n=6) were improved to a high extent. Spatial resolution by an in
      house-built plate holder system was shown to be better than 3 mm. The decay of
      the signal was observed. The efficacy of this new coupling was compared to a
      plunger-based extraction device for HPTLC/electrospray ionisation-MS. The latter
      device showed detectability down to the pg-range, e.g. the limit of
      quantification for isopropylthioxanthone was found to be 100 pg. Repeatability
      was comparable (RSD +/- 6.7%), however, without the need of internal standard
      correction. Analytical response was slightly better and showed a determination
      coefficient R2 of 0.9983. Similar data were obtained for caffeine as well.
      Spatial resolution was 2 mm or 4 mm depending on the plunger head used. The
      comparison showed that HPTLC/DART-TOF-MS is a useful coupling method regarding
      qualitative aspects and it has the potential to cope also with the difficulties
      of quantification if isotope-labeled standards were used or if a plate holder
      system is employed as initially shown.

PMID- 17223116
TI  - Determination of cationic neurotransmitters and metabolites in brain homogenates
      by microchip electrophoresis and carbon nanotube-modified amperometry.
AB  - An electrophoretic method for simultaneous determination of catecholamines and
      their O-methoxylated metabolites on the microchip as well as in the capillary is
      presented. A complex separation system employing sodium dodecyl sulfate (SDS)
      micelles, dendrimers forming a second pseudostationary phase and borate
      complexation is needed for the satisfactory separation of the selected compounds
      on the short migration length. A carbon nanotube-modified working electrode has
      been applied for the sensitive amperometric detection with submicromolar
      detection limits. The applicability of this new method for the analytics of real
      samples is demonstrated by analysis of mouse brain homogenate on the microchip
      and human urine by capillary electrophoresis.

PMID- 17223117
TI  - Simultaneous determination of pharmacologically active ingredients in Rhodiola by
      capillary chromatography with electrochemical detection.
AB  - Rhodiola, in which there are abundant pharmacologically active ingredients, is
      one of the functional adaptogenic agent that aid specific bodily functions to
      adapt to the changes and stress of life in addition to being tonic. In an attempt
      to qualitatively and quantitatively determine the pharmacologically active
      ingredients in Rhodiola, a new method based on capillary electrophoresis with
      electrochemical detection (CE-ED) has been developed. The effects of working
      electrode potential, pH and concentration of running buffer, separation voltage,
      applied potential and injection time on CE-ED were investigated. Under the
      optimum conditions, the analytes could be well separated within 24 min at the
      separation voltage of 18 kV in a 80 mmol L(-1) borax running buffer (pH 9.0).
      Good linear relationship was established between peak current and concentration
      of analytes over two orders of magnitude with detection limits (S/N=3) ranged
      from 3.16 x 10(-7) to 1.11 x 10(-7)g mL(-1) for all target ingredients. This
      proposed method has been successfully applied for the analysis of real samples,
      with satisfactory results.

PMID- 17223118
TI  - Yessotoxin analogues in several strains of Protoceratium reticulatum in Japan
      determined by liquid chromatography-hybrid triple quadrupole/linear ion trap mass
      spectrometry.
AB  - Several strains of Protoceratium reticulatum, one of the dinoflagellates
      producing yessotoxins (YTXs), were collected from various shellfish producing
      areas in Japan. YTXs in the cultured strains were analyzed by liquid
      chromatography-mass spectrometry (LC-MS). Neutral loss scan monitoring, multiple
      reaction monitoring (MRM) for more than 20 YTX analogues, and full-scan MS/MS
      spectra obtained with a hybrid triple quadrupole/linear ion trap mass
      spectrometer showed that yessotoxin (YTX), 45,46,47-trinoryessotoxin (trinorYTX),
      1-homoyessotoxin (homoYTX), and 45,46,47-trinor-1-homoyessotoxin (trinor-1
      homoYTX) were the dominant toxins in these strains of P. reticulatum. Enone
      isomer of 42,43,44,45,46,47,55-heptanor-41-oxoyessotoxin (noroxoYTX enone) was
      also detected in some strains. Toxin profiles and contents were different among
      the strains. Some strains produced YTX, trinorYTX, 1-homoYTX, trinor-1-homoYTX,
      and noroxoYTX enone, whereas other strains produced only YTX or 1-homoYTX. This
      is the first identification of 1-homoYTX and noroxoYTX enone in P. reticulutum in
      Japan. Some strains did not produce any detectable YTX analogues.

PMID- 17223119
TI  - Comparison of various extraction methods for identification and determination of
      volatile metabolites from the brown alga Dictyopteris membranacea.
AB  - Three different methods: hydrodistillation (HD), focused microwave-assisted
      hydrodistillation (FMAHD) and supercritical fluid extraction (SFE) have been
      applied, for the first time together, for the extraction of volatile metabolites
      of the brown alga Dictyopteris membranacea. The oils obtained were analyzed by GC
      MS (identification and determination of metabolites) and the results were
      compared. The main chemical classes of compounds identified were C11 hydrocarbons
      for HD method, sesquiterpenes for FMAHD method and sulphur compounds for SFE
      method.

PMID- 17223120
TI  - Retention behavior of oligomeric proanthocyanidins in hydrophilic interaction
      chromatography.
AB  - A novel method was developed for the separation of proanthocyanidins (PAs;
      oligomeric flavan-3-ols) by hydrophilic interaction chromatography (HILIC) using
      an amide-silica column eluting with an aqueous acetonitrile mobile phase. The
      best separation was achieved with a linear gradient elution of acetonitrile-water
      at ratios of 9:1 to 5:5 (v/v) for 60 min at a flow rate of 1.0 ml/min. Under
      these HPLC conditions, a mixture of natural oligomeric PAs (from apple) was
      separated according to degree of polymerization (DP) up to decamers. The DP of
      each separated oligomer was confirmed by LC/electrospray ionization MS. In
      further HILIC separation studies of 15 different flavan-3-ol and oligomeric PA
      (up to pentamer) standards with an isocratic elution of acetonitrile-water
      (84:16), a high correlation was observed between the logarithm of retention
      factors (log k) and the number of hydroxyl groups in their structures. The
      coefficient of this correlation (r2=0.9501) was larger than the coefficient
      (r2=0.7949) obtained from the correlation between log k and log P(o/w) values.
      These data reveal that two effects, i.e. hydrogen bonding between the carbamoyl
      terminal on the column and the hydroxyl group of solute oligomer and
      hydrophilicity based on the high-order structure of oligomeric PAs, corporately
      contribute to the separation, but the hydrogen bonding effect is predominant in
      our HILIC separation mode.

PMID- 17223121
TI  - Quantitative analysis of bacterial medium-chain-length poly([R]-3
      hydroxyalkanoates) by gas chromatography.
AB  - Standard chromatographic methods for the quantification of bacterial poly(3
      hydroxyalkanoate) (PHA) proved to be inappropriate for the analysis of medium
      chain-length PHA (mcl-PHA). Transesterification catalyzed by protic acids is not
      quantitative for mcl-PHA under common conditions due to slow reaction kinetics
      and formation of side-products in case of functionalized side-chains. To
      circumvent these limitations, an improved method for the quantification of mcl
      PHA by GC-FID was developed. Boron trifluoride in methanol was successfully
      applied to quantitatively methanolyse different mcl-PHA (recovery >94%). This
      novel method is well-suited for the analysis of purified mcl-PHA as well as for
      mcl-PHA in biomass.

PMID- 17223122
TI  - Phase behavior of binary mixture of 1-dodecyl-3-methylimidazolium bromide and
      water revealed by differential scanning calorimetry and polarized optical
      microscopy.
AB  - Phase behavior of aqueous mixture of imidazolium ionic liquid, 1-dodecyl-3
      methylimidazolium bromide, was investigated by means of differential scanning
      calorimetry and polarized optical microscopy. The mixture forms two types of
      lyotropic liquid-crystalline gels, one is composed of lamellar phase and the
      other is of hexagonal phase. T-X phase diagram of the mixture was constructed,
      which defines the regions of various phases appearing in this mixture.

PMID- 17223123
TI  - Preparation of CeO(2)-ZrO(2) ceramic fibers by electrospinning.
AB  - Electrospinning was employed to fabricate polymer-ceramic composite fibers from
      solutions containing poly(vinyl pyrrolidone) (PVP), Ce(NO(3))(3) x 6H(2)O and
      ZrOCl(2) x 8H(2)O. Upon firing the composite fibers at 1000 degrees C,
      Ce(0.67)Zr(0.33)O(2) fibers with diameters ranging from 0.4 to 2 microm were
      synthesized. These fibers exhibit strong resistance to sintering. They still have
      specific surface area around 11.8 m(2)/g after being heated at 1000 degrees C for
      6 h.

PMID- 17223124
TI  - The special theory of Brownian relativity: equivalence principle for dynamic and
      static random paths and uncertainty relation for diffusion.
AB  - The theoretical basis of a recent theory of Brownian relativity for polymer
      solutions is deepened and reexamined. After the problem of relative diffusion in
      polymer solutions is addressed, its two postulates are formulated in all
      generality. The former builds a statistical equivalence between (uncorrelated)
      timelike and shapelike reference frames, that is, among dynamical trajectories of
      liquid molecules and static configurations of polymer chains. The latter defines
      the "diffusive horizon" as the invariant quantity to work with in the special
      version of the theory. Particularly, the concept of universality in polymer
      physics corresponds in Brownian relativity to that of covariance in the Einstein
      formulation. Here, a "universal" law consists of a privileged observation,
      performed from the laboratory rest frame and agreeing with any diffusive
      reference system. From the joint lack of covariance and simultaneity implied by
      the Brownian Lorentz-Poincare transforms, a relative uncertainty arises, in a
      certain analogy with quantum mechanics. It is driven by the difference between
      local diffusion coefficients in the liquid solution. The same transformation
      class can be used to infer Fick's second law of diffusion, playing here the role
      of a gauge invariance preserving covariance of the spacetime increments. An
      overall, noteworthy conclusion emerging from this view concerns the statistics of
      (i) static macromolecular configurations and (ii) the motion of liquid molecules,
      which would be much more related than expected.

PMID- 17223125
TI  - The prevalence of lisping in young adults.
AB  - This paper reports the results of a pilot study that investigated the prevalence
      of lisping in a cohort of young adults. The motivation for the study was the
      observation that a substantial number of incoming students in speech language
      pathology at the Ghent University (Belgium), still presented with frontal lisping
      of the /s/, /z/ and sometimes other alveolar sounds too. Seven hundred and forty
      eight students (374 females, 374 males), native speakers of Dutch, were video
      recorded while reading aloud the Dutch version of the text "The north wind and
      the sun..." from the International Phonetic Association (1974). Analysis of the
      samples yielded an overall prevalence of lisping of 23.3%. Significantly less
      participants presented with lisping among students of humanities than among
      students of natural sciences or social sciences. No significant difference was
      found between males and females. It remains to be determined if this high
      prevalence of lisping in adults represents a recent trend or if the persistence
      of the pattern of lisping into adulthood in some individuals is perhaps quite
      normal. LEARNING OUTCOMES: As a result of this activity, the participant will be
      able to (1) discuss the nature and prevalence of residual phonological errors in
      general and (2) to discuss the prevalence of lisping in young adult native
      speakers of Dutch in particular.

PMID- 17223126
TI  - Tracking antigen-specific CD8+ T cells in the rat using MHC class I multimers.
AB  - Studies of the quantitative and qualitative aspects of anti-microbial, anti
      tumoral or autoreactive immune responses have been greatly facilitated by the
      possibility to stain antigen-specific CD8(+) T cells using fluorescently labeled
      multimeric major histocompatibility complex (MHC) class I/peptide complexes. So
      far, this technology has been developed for human and mouse, but not yet in the
      rat. Here, we describe the generation of the first rat MHC multimer. We produced
      a rat RT1(l) Pro5 MHC Pentamer combined with the immunodominant peptide for Borna
      disease virus (BDV), in order to study the characteristics of the antiviral
      CD8(+) T cell response. BDV is an RNA virus that can cause persistent infections
      of the central nervous system (CNS), often associated with prominent brain
      inflammation. In adult Lewis rats, of the RT1(l) MHC haplotype, BDV infection
      leads to severe immune-mediated neurological symptoms. The pathogenic role of the
      immune response is due primarily to antiviral CD8(+) T cells, many of them being
      specific for an immunodominant epitope located in the BDV nucleoprotein (N(230
      238)). Ex vivo flow cytometry analyses revealed that 3 to 12% of CD8(+) T cells
      found in the brains of BDV-infected rats stained positively with the BDV
      Pentamer. Interestingly, the frequency of Pentamer-positive cells increased up to
      3.3 fold after a short resting period in culture. Virus-specific CD8(+) T cells
      were mainly detected in the brain and were virtually undetectable in peripheral
      lymphoid organs. This novel rat Pro5 MHC Pentamer represents an attractive tool
      for the detection, isolation and characterization of antigen-specific CD8(+) T
      cell responses in the rat.

PMID- 17223127
TI  - Transmission of growth anomalies between Indo-Pacific Porites corals.
AB  - In this study we provide experimental evidence of transmission of growth
      anomalies (GAs) between corals. Twenty-four aquaria (16 experimental, 8
      containing only apparently healthy corals) were set-up on Negros Island,
      Philippines, to test for direct-contact and waterborne transmission of GAs.
      Within seven weeks, two of 16 apparently healthy colonies placed in direct
      contact with colonies having GAs developed multiple GA lesions whose size and
      number increased over time. One of 16 apparently healthy colonies in experimental
      aquaria not touching any diseased colony also developed a GA, exhibiting a single
      lesion that did not increase in size. Apparently healthy colonies (n=24) in
      aquaria without a diseased colony remained unchanged.

PMID- 17223128
TI  - Acute doxorubicin cardiotoxicity is successfully treated with the phytochemical
      oleuropein through suppression of oxidative and nitrosative stress.
AB  - Oleuropein (oleu) is a natural phenolic antioxidant, which is present in elevated
      concentration in olives, olive oil and olive tree leaves. Doxorubicin (DXR)
      induced cardiotoxicity is mainly induced by oxidative stress but the precise
      mechanism remains obscure. However, there is evidence that high concentration of
      nitric oxide (NO) occurring as a result of iNOS induction and peroxynitrite
      formation may be involved in DXR cardiotoxicity. The aim of the present study was
      to evaluate a possible protective role of oleu in DXR induced cardiotoxicity in
      vivo. Fifty rats were divided into 6 groups and treated as follows: control group
      with a single injection of 2 ml normal saline intraperitoneally (i.p.), DXR group
      with a single dose of 20 mg/kg i.p, and DXR plus oleu groups with 20 mg/kg DXR
      i.p. and 100 or 200 mg/kg/BW of oleu i.p. for 5 or 3 consecutive days starting
      either 2 days before or on the day of DXR administration. Seventy-two hours after
      DXR treatment blood samples were collected for creatine phosphokinase (CPK),
      creatine phosphokinase-MB (CPK-MB), lactate dehydrogenase (LDH), aspartate
      aminotransferase (AST) and alanine aminotransferase (ALT) assessments and the
      rats were then sacrificed. Hearts were used for general histology, iNOS
      immunohistochemical and Western blot analysis, and for determination of tissue
      concentrations of lipid peroxidation products, protein carbonyls (PCs), and
      nitrotyrosine (NT). DXR treated animals demonstrated very extensive cytoplasmic
      vacuolisation whereas much less vacuolisation was found in oleu treated groups.
      They also revealed a significant elevation of cardiac enzymes release into
      systemic circulation (P<0.05 vs saline). Both doses of Oleu tested and both
      treatment protocols reduced DXR elevated serum levels of CPK, CPK-MB, LDH, AST
      and ALT (P<0.05). Furthermore, it reduced DXR induced lipid peroxidation, PCs
      content, NT concentration and iNOS induction in myocardial tissue (P<0.05). Oleu
      exerts a protective effect by eliminating DXR induced cardiotoxicity expressed by
      the alteration of intracellular and peripheral markers. Combined oleu and DXR
      treatment improves the therapeutic outcome by preventing undesirable toxicity.

PMID- 17223129
TI  - G-CSF and HGF: combination of vasculogenesis and angiogenesis synergistically
      improves recovery in murine hind limb ischemia.
AB  - Granulocyte colony-stimulating factor (G-CSF) is known to mobilize bone marrow
      stem cells into the peripheral circulation. This study was designed to
      investigate whether G-CSF by itself or in combination with hepatocyte growth
      factor (HGF) can promote vasculogenesis and angiogenesis in murine hind limb
      ischemia. Hind limb ischemia was induced in BALB/c nude or C57/BL6 mice that
      received bone marrow transplantation from green fluorescent protein (GFP)
      transgenic mice. In the HGF group, hHGF expression plasmid was injected into the
      ischemic muscles. In the G-CSF group, G-CSF was administered subcutaneously for
      10 days. The G-CSF+HGF group was concomitantly treated with G-CSF and HGF, and
      the control group received no treatment. All effects were confirmed at 4 weeks.
      The G-CSF+HGF group had a higher laser Doppler blood perfusion index, higher
      microvessel density, and a lower incidence of hind limb necrosis than the other
      groups. Confocal laser microscopy revealed that a number of GFP-positive cells
      infiltrated to the vasculature of the ischemic area. Some of the GFP positive
      cells were clearly co-immunostained with alpha-smooth muscle actin as well as von
      Willebrand factor. G-CSF-mobilized stem cells co-expressed CD49d and CD34, which
      would have promoted their adhesion to cells in the ischemic muscle that expressed
      HGF-induced vascular cell adhesion molecule-1. The combination of G-CSF and HGF
      had a significant synergistic effect, suggesting that the combination of
      mobilization of stem cells from bone marrow to peripheral circulation and their
      recruitment to the ischemic area might potentiate angiogenesis and
      vasculogenesis.

PMID- 17223130
TI  - Stabilization of poliovirus polymerase by NTP binding and fingers-thumb
      interactions.
AB  - The viral RNA-dependent RNA polymerases show a conserved structure where the
      fingers domain interacts with the top of the thumb domain to create a tunnel
      through which nucleotide triphosphates reach the active site. We have solved the
      crystal structures of poliovirus polymerase (3D(pol)) in complex with all four
      NTPs, showing that they all bind in a common pre-insertion site where the
      phosphate groups are not yet positioned over the active site. The NTPs interact
      with both the fingers and palm domains, forming bridging interactions that
      explain the increased thermal stability of 3D(pol) in the presence of NTPs. We
      have also examined the importance of the fingers-thumb domain interaction for the
      function and structural stability of 3D(pol). Results from thermal denaturation
      experiments using circular dichroism and 2-anilino-6-napthaline-sulfonate (ANS)
      fluorescence show that 3D(pol) has a melting temperature of only approximately 40
      degrees C. NTP binding stabilizes the protein and increases the melting by 5-6
      degrees C while mutations in the fingers-thumb domain interface destabilize the
      protein and reduce the melting point by as much as 6 degrees C. In particular,
      the burial of Phe30 and Phe34 from the tip of the index finger into a pocket at
      the top of the thumb and the presence of Trp403 on the thumb domain are key
      interactions required to maintain the structural integrity of the polymerase. The
      data suggest the fingers domain has significant conformational flexibility and
      exists in a highly dynamic molten globule state at physiological temperature. The
      role of the enclosed active site motif as a structural scaffold for constraining
      the fingers domain and accommodating conformational changes in 3D(pol) and other
      viral polymerases during the catalytic cycle is discussed.

PMID- 17223131
TI  - X-ray crystallographic and steady state fluorescence characterization of the
      protein dynamics of yeast polyadenylate polymerase.
AB  - Polyadenylate polymerase (PAP) catalyzes the synthesis of poly(A) tails on the 3'
      end of pre-mRNA. PAP is composed of three domains: an N-terminal nucleotide
      binding domain (homologous to the palm domain of DNA and RNA polymerases), a
      middle domain (containing other conserved, catalytically important residues), and
      a unique C-terminal domain (involved in protein-protein interactions required for
      3'-end formation). Previous X-ray crystallographic studies have shown that the
      domains are arranged in a V-shape such that they form a central cleft with the
      active site located at the base of the cleft at the interface between the N
      terminal and middle domains. In the previous studies, the nucleotides were bound
      directly to the N-terminal domain and exhibited a conspicuous lack of adenine
      specific interactions that would constitute nucleotide recognition. Furthermore,
      it was postulated that base-specific contacts with residues in the middle domain
      could occur either as a result of a change in the conformation of the nucleotide
      or domain movement. To address these issues and to better characterize the
      structural basis of substrate recognition and catalysis, we report two new
      crystal structures of yeast PAP. A comparison of these structures reveals that
      the N-terminal and C-terminal domains of PAP move independently as rigid bodies
      along two well defined axes of rotation. Modeling of the nucleotide into the most
      closed state allows us to deduce specific nucleotide interactions involving
      residues in the middle domain (K215, Y224 and N226) that are proposed to be
      involved in substrate binding and specificity. To further investigate the nature
      of PAP domain flexibility, 2-aminopurine labeled molecular probes were employed
      in steady state fluorescence and acrylamide quenching experiments. The results
      suggest that the closed domain conformation is stabilized upon recognition of the
      correct subtrate, MgATP, in an enzyme-substrate ternary complex. The implications
      of these results on the enzyme mechanism of PAP and the possible role for domain
      motion in an induced fit mechanism are discussed.

PMID- 17223132
TI  - Beyond dimerization: a membrane-dependent activation model for interleukin-4
      receptor-mediated signalling.
AB  - Class I cytokine receptors efficiently transfer activation signals from the
      extracellular space to the cytoplasm and play a dominant role in growth control
      and differentiation of human tissues. Although a significant body of literature
      is devoted to this topic, a consistent mechanistic picture for receptor
      activation in the membrane environment is still missing. Using the interleukin-4
      receptor (IL-4R) as an example, we propose that the membrane-proximal stem-loop
      of the extracellular domains contains pivotal elements of a rotational switch.
      Interfacial energies of amino acid side-chains contained in the highly conserved
      WSXWS at the surface of the lipid bilayer suggest a new functional role for this
      motif. A generic activation mechanism for this receptor class is presented, which
      may impact the design of a new generation of biophysical assay systems.

PMID- 17223133
TI  - Structure of the Escherichia coli leucine-responsive regulatory protein Lrp
      reveals a novel octameric assembly.
AB  - The structure of Escherichia coli leucine-responsive regulatory protein (Lrp) co
      crystallized with a short duplex oligodeoxynucleotide reveals a novel quaternary
      assembly in which the protein octamer forms an open, linear array of four dimers.
      In contrast, structures of the Lrp homologs LrpA, LrpC and AsnC crystallized in
      the absence of DNA show that these proteins instead form highly symmetrical
      octamers in which the four dimers form a closed ring. Although the DNA is
      disordered within the Lrp crystal, comparative analyses suggest that the observed
      differences in quaternary state may arise from DNA interactions during
      crystallization. Interconversion of these conformations, possibly in response to
      DNA or leucine binding, provides an underlying mechanism to alter the relative
      spatial orientation of the DNA-binding domains. Breaking of the closed octamer
      symmetry may be a common essential step in the formation of active DNA complexes
      by all members of the Lrp/AsnC family of transcriptional regulatory proteins.

PMID- 17223134
TI  - Calculation of pKas in RNA: on the structural origins and functional roles of
      protonated nucleotides.
AB  - pK(a) calculations based on the Poisson-Boltzmann equation have been widely used
      to study proteins and, more recently, DNA. However, much less attention has been
      paid to the calculation of pK(a) shifts in RNA. There is accumulating evidence
      that protonated nucleotides can stabilize RNA structure and participate in enzyme
      catalysis within ribozymes. Here, we calculate the pK(a) shifts of nucleotides in
      RNA structures using numerical solutions to the Poisson-Boltzmann equation. We
      find that significant shifts are predicted for several nucleotides in two
      catalytic RNAs, the hairpin ribozyme and the hepatitis delta virus ribozyme, and
      that the shifts are likely to be related to their functions. We explore how
      different structural environments shift the pK(a)s of nucleotides from their
      solution values. RNA structures appear to use two basic strategies to shift
      pK(a)s: (a) the formation of compact structural motifs with structurally
      conserved, electrostatic interactions; and (b) the arrangement of the
      phosphodiester backbone to focus negative electrostatic potential in specific
      regions.

PMID- 17223135
TI  - Sherrington's "The Integrative action of the nervous system": a centennial
      appraisal.
AB  - The Integrative Action of the Nervous System by the British physiologist Charles
      Sherrington was published 100 years ago. Its goal was to explain how the nervous
      system welds a collection of disparate body parts and organs into a unified
      individual. Sherrington postulated that the reflex is the simplest unit of
      nervous integration. He introduced the concept of the synapse as the site where
      elementary reflexes interact to enable more complex and unified behavior and
      argued that a synaptic nervous system facilitated the evolution of the cerebrum
      and cerebellum. The concept of the synapse as a physiological entity provided a
      theoretical schema into which the richly varied phenomenology of nineteenth
      century reflex physiology could be assimilated. Sherrington's book also provided
      the conceptual framework for a century of research into the mechanisms of
      synaptic transmission and the neuronal discharges associated with perception and
      action.

PMID- 17223136
TI  - Time course of vascular arginase expression and activity in spontaneously
      hypertensive rats.
AB  - There is growing evidence that vascular arginase plays a role in pathophysiology
      of vascular diseases. We recently reported high arginase activity/expression in
      young adult hypertensive spontaneously hypertensive rats (SHR). The aim of the
      present study was to characterize the time course of arginase pathway
      abnormalities in SHR and to explore the contributing role of hemodynamics and
      inflammation. Experiments were conducted on 5, 10, 19 and 26-week-old SHR and
      their age-matched control Wistar Kyoto (WKY) rats. Arginase activity as well as
      expression of arginase I, arginase II, endothelial and inducible NOS were
      determined in aortic tissue extracts. Levels of L-arginine, NO catabolites and IL
      6 (a marker of inflammation) were measured in plasma. Arginase
      activity/expression was also measured in 10-week-old SHR previously treated with
      hydralazine (20 mg/kg/day, per os, for 5 weeks). As compared to WKY, SHR
      exhibited high vascular arginase I and II expression from prehypertensive to
      established stages of hypertension. However, a mismatch between expression and
      activity was observed at the prehypertensive stage. Arginase expression was not
      related either to plasma IL-6 levels or to expression of NOS. Prevention of
      hypertension by hydralazine significantly blunted arginase upregulation and
      restored arginase activity. Importantly, arginase activity and blood pressure
      (BP) correlated in SHR. In conclusion, our results demonstrate that arginase
      upregulation precedes blood pressure rising and identify elevated blood pressure
      as a contributing factor of arginase dysregulation in genetic hypertension. They
      also demonstrated a close relationship between arginase activity and BP, thus
      making arginase a promising target for antihypertensive therapy.

PMID- 17223137
TI  - Aquaculture and transport in a changing environment: overlap and links in the
      spread of alien biota.
AB  - Aquaculture has been practiced for some millennia. The speed and access of
      different transport modes in the spread of cultured species, their pests,
      parasites, diseases and associates, has changed over this time. There now exists
      an overlap and interlinking of different transport networks with further routes
      planned. Coupled with environmental changes and habitat alterations alien biota
      are presented with further opportunities to become more widely distributed. The
      certainty of the responsible pathway for the arrival of an alien species is not
      always easily deduced unless imported directly. A scheme for classifying
      different levels of certainty is proposed. Aquaculture itself consists of
      different cultivation intensities ranging from part to all of a species life
      history and are classified accordingly in this account. It is inevitable that
      further species intended for cultivation will be utilized in different world
      regions and that other biota, some considered to be harmful, will also be
      transmitted. Nevertheless there are codes of practice such as those used by the
      IMO and ICES that can reduce some risks.

PMID- 17223138
TI  - Ecosystem objectives to support the UK vision for the marine environment.
AB  - European Maritime States already have commitments to protect species and habitats
      and maintain quality standards in coastal and offshore waters. These are a direct
      response to environmental legislation in Europe and commitments made to
      biodiversity conservation in OSPAR and at the World Summit on Sustainable
      Development. An integrated approach to management requires that these are
      consistent with the requirements for sustainable development, and include wider
      social considerations and active stakeholder participation. This review describes
      a hierarchical framework that incorporates the marine objectives and delivery
      statements of ecological, social and economic sectors. The framework leads from
      the UK's guiding principles for sustainable development, through visionary
      statements and strategic goals for high level delivery, to operational objectives
      and statements of action which deliver management. Parts of this hierarchy can
      already be populated for the UK, especially those at the higher levels. At the
      operational level, however, there is less clarity. The review shows that, despite
      some gaps, existing commitments for ecological components of the ecosystem are
      transparent and generally conform to this framework, due largely to high profile
      government funding of environmental protection and science and a single national
      vision for the marine environment. Specific objectives for six components of the
      ecosystem were developed; benthic habitats, seabirds and mammals, phytoplankton
      and zooplankton, fish, and physical/chemical quality of the water and atmosphere.
      The objectives included some that avoided limits and others that aimed to achieve
      targets, and for management to be effective it will be important to have a common
      understanding of how these can together be interpreted and made operational. In a
      review of 13 social and economic sectors, few provided a clear breakdown of
      objectives leading from a high level vision or a sustainable development
      principle. Six sectors did not have high level government targets for production
      or other measures of sectoral performance. Such commercial operations generally
      determine their own operational delivery targets based on market forces. Recent
      proposals in Europe to create an integrated framework for social, economic and
      environmental activities will need to carefully balance the development of a
      strong and competitive marine economy with existing international obligations to
      environmental protection.

PMID- 17223140
TI  - Effects of ability- and chance-determined competition outcome on testosterone.
AB  - Winning competitions has been shown to lead to higher testosterone (T) relative
      to losing in men and males of other species. In Experiment 1, 38 women and 37 men
      provided a saliva sample, completed a novel computer-based vocabulary competition
      task at which they won or lost based on their own ability, provided feedback
      about the competition via questionnaire, and then produced a second saliva
      sample. Task outcome and performance was not sexually differentiated, and overall
      task performance was negatively correlated with T. Male but not female winners
      had lower baseline and post-competition T, and male losers had a larger decrease
      in T from baseline to post-competition. In Experiment 2, 31 men and 43 women
      completed the same as above, but were randomly assigned to win or lose. In this
      case, competition outcome did not affect T for men but there was an effect such
      that women who would have had an ability-determined loss showed a larger decrease
      in T than women who would have had an ability-determined win. Thus, earned wins
      appear to attenuate a decline in T in men, consistent with past research into the
      competition effect and T, and perhaps women under complex circumstances.

PMID- 17223139
TI  - Improved growth factor directed vascularization into fibrin constructs through
      inclusion of additional extracellular molecules.
AB  - Using the chick chorioallantoic membrane assay (CAM) and a novel histological
      technique, we investigated the ability of blood vessels to directly invade fibrin
      based scaffolds. In our initial experiments utilizing vascular endothelial growth
      factor (VEGF(165)), we found no direct invasion. Instead, the fibrin was
      completely degraded and replaced with highly vascularized new tissue. Addition of
      fibroblast growth factor-2 (FGF-2), bone morphogenic protein-2 (BMP-2), or
      platelet-derived growth factor-BB (PDGF-BB) to the fibrin construct also did not
      result in construct vascularization. Because natural and regenerating tissues
      exhibit complex extracellular matrices (ECMs), we hypothesized that a more
      complex scaffold may improve blood vessel invasion. Addition of fibronectin,
      hyaluronic acid, and collagen type I within 20 mg/mL fibrin constructs resulted
      in no significant improvement. However, the same additive concentrations within
      10 mg/mL fibrin constructs resulted in dramatic improvements, specifically with
      hyaluronic acid. Overall, we believe that these results indicate the importance
      of structural and functional cues of not only in the initial scaffold but also as
      the construct is degraded and remodeled. Furthermore, the CAM assay may represent
      a useful model for understanding ECM interactions as well as for screening and
      designing tissue-engineered scaffolds.

PMID- 17223141
TI  - Galanin type 1 receptor knockout mice show altered responses to high-fat diet and
      glucose challenge.
AB  - Galanin, a brain and pancreatic peptide with three receptor subtypes (GALR1,
      GALR2, and GALR3), is hypothesized to participate in energy homeostasis and
      glucoregulation. Hypothalamic galanin expression is induced by dietary fat, and
      intra-hypothalamic galanin administration has orexigenic/anabolic properties.
      Systemic galanin infusion alters glucoregulation in non-human species, partly
      through direct actions on pancreatic islets. However, the physiologic
      significance of endogenous galanin-GALR signaling is unclear. The present studies
      tested the hypotheses that GALR1 deficiency alters food intake and feed
      efficiency following switches to high-fat diet and that GALR1 deficiency alters
      whole-body glucose homeostasis. Adult, male GALR1 knockout (-/-), heterozygote
      (+/-), and C57BL/6J control (+/+) mice were studied. GALR1 deficiency impaired
      adaptation to a 3-day high-fat diet challenge, leading to increased food intake,
      feed efficiency and weight gain. However, during the following 2 weeks, GALR1
      knockout mice decreased intake, consuming less daily energy than while maintained
      on low-fat diet and also than heterozygote littermates. Chow-maintained GALR1
      knockout mice showed relative hyperglycemia in fed and d-glucose (i.p. 1.5 g/kg)
      challenged states. GALR1 knockout mice showed normal food intake, feed efficiency
      and weight accrual on low-fat diets, normal fasted glucose levels, and normal
      glucose sensitivity to porcine insulin (i.p. 1 IU/kg) in vivo. The results
      support the hypotheses that galanin-GALR1 systems help adapt food intake and
      metabolism to changes in dietary fat and modulate glucose disposition in mice.

PMID- 17223142
TI  - Identification of very long chain unsaturated fatty acids from Ximenia oil by
      atmospheric pressure chemical ionization liquid chromatography-mass spectroscopy.
AB  - A method is described for the enrichment of very long chain unsaturated fatty
      acids from total fatty acids of Ximenia oil and their identification as picolinyl
      esters by means of liquid chromatography-mass spectrometry with atmospheric
      pressure chemical ionization (LC-MS/APCI). The method is based on the use of
      preparative reversed phase HPLC and their subsequent identification by microbore
      LC-MS/APCI. The combination of these two techniques was used to identify unusual
      unsaturated VLCFAs up to tetracontenoic acid. All four positional isomers of
      tetratriacontenoic acid were also synthesized to unambiguously confirm their
      structure.

PMID- 17223143
TI  - Public understanding of toxocariasis.

PMID- 17223144
TI  - Smoking habits and associated factors among Greek physicians.
AB  - OBJECTIVE: To investigate the smoking habits and associated risk factors among
      Greek physicians. STUDY DESIGN: Cross-sectional survey of a randomly selected
      sample of Greek physicians. METHODS: A national sample of 1284 physicians (718
      men, 566 women) participated in the study, which was conducted between September
      2003 and June 2005. Data were collected through an anonymous self-completed
      questionnaire. Logistic regression was used to analyse the influence of different
      factors on the probability of a physician being a current or former smoker.
      RESULTS: Overall, 38.6% of the physicians (40% of men; 37% of women) currently
      smoked, 13.8% were former smokers, and 47.6% had never smoked. Eighty-three per
      cent of smokers reported starting smoking before the age of 25 years, with half
      of them during medical school (aged 19-24 years). Multivariate analyses revealed
      that physicians who were male, unmarried, divorced or widowed, surgeons or
      anaesthetists, and residents were more likely to be current smokers. Former
      smokers were more likely to be older, male and born in a rural area. Moreover,
      the odds of being a current or former smoker were significantly higher among
      physicians with a history of parents who smoked. The proportion of physicians who
      reported counselling patients (often or always) to stop smoking was lower among
      current smokers compared with those who never smoked or those who were former
      smokers (74.4% vs. 85.3% vs. 84.7%, P<0.0001). CONCLUSIONS: The prevalence of
      smoking among Greek physicians is exceedingly high and similar to that of the
      general population. More effective interventions that reduce smoking in the
      medical community should be implemented immediately so that physicians will be
      better able to fulfil their function as role models for the general population.

PMID- 17223145
TI  - The levels of PCV2 specific antibodies and viremia in pigs.
AB  - Porcine circovirus 2 quantification by real-time PCR and determination of virus
      specific antibodies using a peptide based ELISA test was performed on a total of
      400 serum samples. Samples for antibody measurement and virus quantification were
      obtained from a conventional pig farm with a clinical form of post-weaning
      multisystemic wasting syndrome. Samples were taken during the post-weaning
      period. Seven litters of weaned piglets (6-25 weeks) were systematically sampled
      at 2-3 week intervals. Porcine circovirus 2 specific antibodies were detected
      using the peptide based ELISA test. IgM antibodies were first detected at week 8
      and reached their highest levels at week 12; IgG antibody appeared at week 10 and
      peaked at week 16 with an average titer at 1:3500. Although, the viral load
      peaked at week 10 (7x10(7) genomes copy/ml of sera), viral infection persisted
      through to adult age (10(5) genomes copy/ml of sera).

PMID- 17223146
TI  - CpG oligodeoxynucleotides augment the immune responses of piglets to swine
      Pasteurella multocida living vaccine in vivo.
AB  - Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) prevent
      development of T-helper type 2 (Th2) immune response and reverse established
      allergic responses in mouse models. However, little work on immune responses in
      piglets has been conducted in vivo. In this report, the ability of a porcine
      specific CpG ODN to act as an immunostimulant and enhance immune responses of
      piglets to swine Pasteurella multocida living vaccine (SPML vaccine) was
      determined. The titre of IgG and IgG1/IgG2 isotype to SPML vaccine in serum, the
      proliferation of lymphocytes, SPML-specific interferon-gamma (IFN-gamma) and IL
      6, TNF-alpha, IL-4 production of PBMCs in vitro and IFN-gamma, IL-6, TNF-alpha,
      IL-4, IL-10 in piglets serum were examined to identify the immune responses of
      the piglets. Immune responses of the piglets vaccinated with SPML and CpG ODN
      were significantly stronger than responses of piglets vaccinated with SPML alone.
      All these data summarized that immunostimulatory CpG ODN could modulate the
      immune response towards a Th1-like response when co-administered to piglets
      during SPML vaccination, which suggested that the therapeutic uses envisioned for
      these ODNs (as vaccine adjuvants and immunoprotective agents) may be applicable
      to husbandry animals.

PMID- 17223147
TI  - Comparative non-cholinergic neurotoxic effects of paraoxon and diisopropyl
      fluorophosphate (DFP) on human neuroblastoma and astrocytoma cell lines.
AB  - The objective of this study was to evaluate the comparative non-cholinergic
      neurotoxic effects of paraoxon, which is acutely neurotoxic, and diisopropyl
      fluorophosphate (DFP), which induces OPIDN, in the human neuroblastoma SY5Y and
      the human astrocytoma cell line CCF-STTG1. SY5Y cells have been studied
      extensively as a model for OP-induced neurotoxicity, but CCF cells have not
      previously been studied. We conducted a preliminary human gene array assay of OP
      treated SY5Y cells in order to assess at the gene level whether these cells can
      distinguish between OP compounds that do and do not cause OPIDN. Paraoxon and DFP
      induced dramatically different profiles of gene expression. Two genes were
      upregulated and 13 downregulated by at least 2-fold in paraoxon-treated cells. In
      contrast, one gene was upregulated by DFP and none was downregulated at the 2
      fold threshold. This finding is consistent with current and previous observations
      that SY5Y cells can distinguish between OPs that do or do not induce OPIDN. We
      also examined gene array results for possible novel target proteins or metabolic
      pathways for OP neurotoxicity. Protein levels of glucose regulated protein 78
      (GRP78) revealed that paraoxon exposure at 3 microM for 24 h significantly
      reduced GRP78 levels by 30% in neuroblastoma cells, whereas DFP treatment had no
      effect. In comparison with SY5Y neuroblastoma cells, paraoxon and DFP (3 microM
      for 24 h) each significantly increased GRP78 levels by 23-24% in CCF astrocytoma
      cells. As we have previously evaluated intracellular changes in Ca(2+) levels in
      SY5Y cells, we investigated the effects of paraoxon and DFP on cellular Ca(2+)
      homeostasis in CCF by studying cytosolic and mitochondrial basal calcium levels.
      A significant decrease in the ratio of mitochondrial to cytosolic Ca(2+)
      fluorescence was detected in CCF cultures treated for either 1 or 3 days with 1,
      3, 10, or 30 microM paraoxon. In contrast, treatment with DFP for 1 day had no
      significant effect on the ratio of mitochondrial to cytosolic Ca(2+)
      fluorescence; after 3 days treatment, only 30 microM decreased the ratio. These
      results are consistent with the finding that paraoxon induced a greater decrease
      than did DFP of intracellular esterase activity in CCF cells. The changes seen in
      the ratio of mitochondrial to cytosolic Ca(2+) represent a good indicator of the
      degree of injury induced by each chemical tested. This work further develops in
      vitro models that distinguish between compounds that cause OPIDN and those that
      induce acute neurotoxicity only. The study also exposes additional OP-induced
      toxicities that may be obscured in vivo.

PMID- 17223148
TI  - Fighting the global pest problem: preface to the special Toxicon issue on
      insecticidal toxins and their potential for insect pest control.
AB  - Arthropod pests are responsible for major crop devastation and are vectors for
      the transmission of new and re-emerging diseases in humans and livestock. Despite
      many years of effective control by conventional agrochemical insecticides, a
      number of factors are threatening the effectiveness and continued use of these
      agents. These include the development of insecticide resistance and use
      cancellation or de-registration of some insecticides due to human health and
      environmental concerns. Several approaches are being investigated for the design
      of new (bio)pesticides. These include the development of transgenic plants and
      recombinant baculoviruses as delivery systems for a variety of insect-selective
      toxins. Additional approaches for the development of foliar sprays include the
      rational design of peptidomimetics based on the key residues of these toxins that
      interact with the insect target. This special issue provides an overview of these
      phyletically selective animal, plant and microbial toxins and their diverse
      mechanisms of action to paralyze or kill arthropods. In addition, it reviews
      their potential for biopesticide discovery and validation of novel insecticide
      targets and provides an overview of the strengths and weaknesses of biopesticides
      in the global control of arthropod pests.

PMID- 17223149
TI  - Insect-selective spider toxins targeting voltage-gated sodium channels.
AB  - The voltage-gated sodium (Na(v)) channel is a target for a number of drugs,
      insecticides and neurotoxins. These bind to at least seven identified neurotoxin
      binding sites and either block conductance or modulate Na(v) channel gating. A
      number of peptide neurotoxins from the venoms of araneomorph and mygalomorph
      spiders have been isolated and characterized and determined to interact with
      several of these sites. These all conform to an 'inhibitor cystine-knot' motif
      with structural, but not sequence homology, to a variety of other spider and
      marine snail toxins. Of these, spider toxins several show phyla-specificity and
      are being considered as lead compounds for the development of biopesticides.
      Hainantoxin-I appears to target site-1 to block Na(v) channel conductance. Magi 2
      and Tx4(6-1) slow Na(v) channel inactivation via an interaction with site-3. The
      delta-palutoxins, and most likely mu-agatoxins and curtatoxins, target site-4.
      However, their action is complex with the mu-agatoxins causing a hyperpolarizing
      shift in the voltage-dependence of activation, an action analogous to scorpion
      beta-toxins, but with both delta-palutoxins and mu-agatoxins slowing Na(v)
      channel inactivation, a site-3-like action. In addition, several other spider
      neurotoxins, such as delta-atracotoxins, are known to target both insect and
      vertebrate Na(v) channels most likely as a result of the conserved structures
      within domains of voltage-gated ion channels across phyla. These toxins may
      provide tools to establish the molecular determinants of invertebrate
      selectivity. These studies are being greatly assisted by the determination of the
      pharmacophore of these toxins, but without precise identification of their
      binding site and mode of action their potential in the above areas remains
      underdeveloped.

PMID- 17223150
TI  - Herpes simplex virus type 1 tegument proteins VP1/2 and UL37 are associated with
      intranuclear capsids.
AB  - The assembly of the tegument of herpes simplex virus type 1 (HSV-1) is a complex
      process that involves a number of events at various sites within virus-infected
      cells. Our studies focused on determining whether tegument proteins, VP1/2 and
      UL37, are added to capsids located within the nucleus. Capsids were isolated from
      the nuclear fraction of HSV-1-infected cells and purified by rate-zonal
      centrifugation to separate B capsids (containing the scaffold proteins and no
      viral DNA) and C capsids (containing DNA and no scaffold proteins). Western blot
      analyses of these capsids indicated that VP1/2 associated primarily with C
      capsids and UL37 associated with B and C capsids. The results demonstrate that at
      least two of the tegument proteins of HSV-1 are associated with capsids isolated
      from the nuclear fraction, and these capsid-tegument protein interactions may
      represent initial events of the tegumentation process.

PMID- 17223151
TI  - Early depletion of proliferating B cells of germinal center in rapidly
      progressive simian immunodeficiency virus infection.
AB  - Lack of virus specific antibody response is commonly observed in both HIV-1
      infected humans and SIV-infected monkeys with rapid disease progression. However,
      the mechanisms underlying this important observation still remain unclear. In a
      titration study of a SIVmac239 viral stock, three out of six animals with viral
      inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was
      no obvious depletion of CD4(+) T cells in both peripheral and lymph node (LN)
      compartments in these animals. Instead, progressive depletion of proliferating B
      cells and disruption of the follicular dendritic cell (FDC) network in germinal
      centers (GC) was evident in the samples collected at as early as 20 days after
      viral challenge. This coincided with undetectable, or weak and transient, virus
      specific antibody responses over the course of infection. In situ hybridization
      of SIV RNA in the LN samples revealed a high frequency of SIV productively
      infected cells and large amounts of accumulated viral RNA in the GCs in these
      animals. Early severe depletion of GC proliferating B cells and disruption of the
      FDC network may thus result in an inability to mount a virus-specific antibody
      response in rapid progressors, which has been shown to contribute to accelerated
      disease progression of SIV infection.

PMID- 17223152
TI  - Immunological changes and cytokine gene expression during primary infection with
      human T-cell leukaemia virus type 1 in squirrel monkeys (Saimiri sciureus).
AB  - We have developed an animal model of experimental HTLV-1 infection in Saimiri
      sciureus monkeys in order to study both the immunological and the virological
      aspects of the infection. As cytokines expressed by immune cells play an
      essential role during viral infection, we have studied the correlation between
      the expression of some Th1/Th2 cytokines, including IL-2, IL-5, IL-6, IL-10, and
      IFN-gamma, and immunological dynamics during primary and chronic HTLV-1 infection
      in this model. We first demonstrated that, during primary infection, IFN-gamma,
      IL-2 and IL-10 are expressed at different times and levels. The expression of
      these cytokines is concomitant with the increase in the numbers of CD4(+), CD8(+)
      and CD16(+) cells and with the presence of tax/rex viral mRNA. These data
      indicate the involvement of various cell types in the antiviral immune response.
      Subsequently, we showed that peripheral blood mononuclear cells freshly isolated
      from chronically infected monkeys express IFN-gamma and IL-6 at higher levels
      than those from uninfected animals. IFN-gamma expression is quantitatively
      correlated to the proviral load and to the presence of circulating effector T
      cells against Tax peptide, as detected by Elispot. Further studies will be needed
      to determine the effective role of these cytokines and other immune system
      modulators in the control of viral replication during primary HTLV-1 infection or
      latency.

PMID- 17223153
TI  - Shift in spatial scale in identifying crowded letters.
AB  - Crowding refers to the increased difficulty in identifying a letter flanked by
      other letters. The purpose of this study was to determine if the peak sensitivity
      of the human visual system shifts to a different spatial frequency when
      identifying crowded letters, compared with single letters. We measured contrast
      thresholds for identifying the middle target letters in trigrams, for a range of
      spatial frequencies, letter separations and letter sizes, at the fovea and 5
      degrees eccentricity. Plots of contrast sensitivity vs. letter frequency exhibit
      spatial tuning, for all letter sizes and letter separations tested. The peak
      tuning frequency grows as the 0.6-0.7 power of the letter size, independent of
      letter separation. At the smallest letter separation, peak tuning frequency
      occurs at a frequency that is 0.17 octaves higher for flanked than for unflanked
      letters at the fovea, and 0.19 octaves at 5 degrees eccentricity. This finding
      suggests that the human visual system shifts its sensitivity toward a higher
      spatial-frequency channel when identifying letters in the presence of nearby
      letters. However, the size of the shift is insufficient to account for the large
      effect of crowding in the periphery.

PMID- 17223154
TI  - Conceptual model of human blur perception.
AB  - An empirically based, conceptual model of human blur perception is presented. It
      incorporates the concepts of blur detection and blur discrimination in depth, and
      across the central and peripheral retina, in two- and three-dimensional visual
      space. Key aspects of the model are its dynamic nature, predictability regarding
      the blur-based depth-ordering of objects, patterns of retinal defocus with far
      and near viewing, and interactions related to retinal defocus between the central
      and peripheral retina. Furthermore, a two-dimensional schematic representation of
      the blur-free region during near viewing is depicted in dioptric space. This
      model has implications with respect to accommodative control, depth perception,
      and refractive error development and progression.

PMID- 17223155
TI  - Global contour processing in amblyopia.
AB  - The purpose of the experiments described here was to investigate global image
      processing using methods that require global processing while eliminating or
      compensating for low level abnormalities: visibility, shape perception and
      positional uncertainty. In order to accomplish this we used a closed figure made
      up of Gabor patches either in noise or on a blank field. The stimuli were
      circular or elliptical contours, formed by N equally spaced Gabor patches. We
      performed two separate experiments: In one experiment we fixed N and varied the
      aspect ratio using a staircase to determine the threshold aspect ratio; in the
      second experiment we held the aspect ratio constant (at twice the threshold
      aspect ratio) and varied N in order to measure the threshold number of elements
      required to judge the shape. Our results confirm and extend previous studies
      showing that humans with naturally occurring amblyopia show deficits in contour
      processing. Our results show that the deficits depend strongly on spatial scale
      (target size and spatial frequency). The deficit in global contour processing is
      substantially greater in noise (where contour-linking is required) than on a
      blank field. The magnitude of the deficits is modest when low-level deficits
      (reduced visibility, increased positional uncertainty, and abnormal shape
      perception) are minimized, and does not seem to depend much on acuity, crowding
      or stereoacuity. The residual deficits reported here cannot be simply ascribed to
      reduced visibility or increased positional uncertainty, and we therefore conclude
      that these are genuine deficits in global contour segregation and integration.

PMID- 17223156
TI  - Assessing nutrient flows in septic tanks by eliciting expert judgement: a
      promising method in the context of developing countries.
AB  - Simple models based on the physical and biochemical processes occurring in septic
      tanks, pit and urine diversion latrines were developed to determine the nutrient
      flows in these systems. Nitrogen and phosphorus separation in different output
      materials from these on-site sanitation installations were thus determined.
      Moreover, nutrient separation in septic tanks was also assessed through
      literature values and by eliciting expert judgement. Use of formal expert
      elicitation technique proved to be effective, particularly in the context of
      developing countries where data is often scarce but expert judgement readily
      available. In Vietnam, only 5-14% and 11-27% of the nitrogen and phosphorus
      input, respectively, are removed from septic tanks with the faecal sludge. The
      remaining fraction leaves the tank via the liquid effluent. Unlike septic tanks,
      urine diversion latrines allow to immobilize most of the nutrients either in form
      of stored urine or dehydrated faecal matter. These latrines thus contribute to
      reducing the nutrient load in the environment and lowering consumption of energy
      and non-renewable resources for fertiliser production.

PMID- 17223157
TI  - Sensory aspects and water quality impacts of chlorinated and chloraminated
      drinking water in contact with HDPE and cPVC pipe.
AB  - Pipes constructed with high-density polyethylene (HDPE) or chlorinated polyvinyl
      chloride (cPVC) are commonly used in drinking water distribution systems and
      premise plumbing. In this comprehensive investigation, the effects on odor,
      organic chemical release, trihalomethane (THM) formation, free chlorine demand
      and monochloramine demand were determined for water exposed to HDPE and cPVC
      pipes. The study was conducted in accordance with the Utility Quick Test (UQT), a
      migration/leaching protocol for analysis of materials in contact with drinking
      water. The sensory panel consistently attributed a weak to moderate intensity of
      a "waxy/plastic/citrus" odor to the water from the HDPE pipes but not the cPVC
      contacted water samples. The odor intensity generated by the HDPE pipe remained
      relatively constant for multiple water flushes, and the odor descriptors were
      affected by disinfectant type. Water samples stored in both types of pipe showed
      a significant increase in the leaching of organic compounds when compared to
      glass controls, with HDPE producing 0.14 microgTOC/cm(2) pipe surface, which was
      significantly greater than the TOC release from cPVC. Water stored in both types
      of pipe showed disinfectant demands of 0.1-0.9 microg disinfectant/cm(2) pipe
      surface, with HDPE exerting more demand than cPVC. No THMs were detected in
      chlorinated water exposed to the pipes. The results demonstrate the impact that
      synthetic plumbing materials can have on sensory and chemical water quality, as
      well as the significant variations in drinking water quality generated from
      different materials.

PMID- 17223158
TI  - Detoxification of kraft pulp ECF bleaching effluents by catalytic hydrotreatment.
AB  - Two different effluents from the D(1) and E(1) stages of the ECF bleaching of
      Eucalyptus globulus kraft pulp were treated by catalytic hydrogenation in a
      trickle bed reactor using commercial and homemade Pd/AC catalysts. The reactor
      was fed with the bleaching effluent and a H(2)/N(2) gas stream. The variables
      studied were space-time (1.4-5g(cat)min/mL), gas to liquid flow ratio (286
      1000vol.), gas feed concentration (H(2):N(2), 1:1-1:7.3vol.), temperature (25-100
      degrees C) and pressure (1-11bar). Hydrotreatment performance was evaluated in
      terms of ecotoxicity, adsorbable organic halogen (AOX), chemical oxygen demand
      (COD), biological oxygen demand (BOD(5)) and colour removal. In all the runs, the
      ecotoxicity of the effluents decreased as a result of the treatment, achieving
      reductions that ranged from 70% to 98%. Simultaneously to the reduction of
      toxicity, the hydrotreatment led to a decrease of the colour of the effluents,
      being the decrease significantly higher in the case of E(1) effluent. The AOX
      content was reduced by 85% and 23% for E(1) and D(1) effluents, respectively. In
      the case of D(1) effluent the removal of ecotoxicity was significantly higher
      than that of AOX, which indicates that much of the toxicity of the effluent must
      be associated to non-chlorinated organics. In spite of the important reduction of
      ecotoxicity, the biodegradability of the effluents only increased slightly. The
      homemade catalysts, prepared from activated carbons with a high external or non
      microporous surface area and mesopore volume and a convenient surface chemistry
      showed a higher efficiency than the commercial one.

PMID- 17223159
TI  - Effect of feeding pattern on biochemical storage by activated sludge under anoxic
      conditions.
AB  - This study investigated the effect of feeding pattern on bacterial storage under
      anoxic conditions, emphasizing previous adaptation of biomass to a long term
      feeding condition, under steady-state operation. Storage was evaluated in a
      sequencing batch reactor (SBR) system operated in a sequence of anoxic/aerobic
      phases, fed with acetate as the sole carbon source during anoxic conditions. The
      experimental results indicated that biochemical storage of acetate as PHB
      occurred when substrate was fed as a pulse, while acetate was removed mostly
      through direct microbial growth under continuous feeding. For pulse feeding, the
      anoxic yield, Y(STOD) was calculated as 0.58mg COD (mgCOD)(-1) in two different
      ways, using mass balances on acetate utilization, PHB generation and nitrate
      consumption. This value was supported by parallel batch tests and similar results
      in the literature. Similarly, the rate coefficient for storage under anoxic
      conditions, k(STOD) was computed as 9.3day(-1) based on basic stoichiometry and
      model calibration of experimental data. Batch tests conducted with biomass
      adapted to different feeding patterns showed that substrate storage was
      insignificant when the feed was added continuously at low concentrations, even if
      the biomass was previously adapted to storage. Similarly biomass acclimated to
      continuous feeding could not store the excess substrate although fed instantly.
      For the operating conditions selected for the study, storage response was
      significant only with a microbial culture with metabolic activities previously
      adapted to storage and with short-term substrate feeding at high concentrations.

PMID- 17223160
TI  - Design, synthesis and melatoninergic potency of new N-acyl 8,9-dihydro-4-methoxy
      7H-2-benzo[de]quinolinalkanamines.
AB  - A series of new N-acyl 8,9-dihydro-4-methoxy-7H-2-benzo[de]quinolinalkanamines
      have been prepared and tested for their ability to activate pigment granule
      aggregation in Xenopus laevis melanophores and bind to the recombinant human
      MT(1) and MT(2) melatonin receptor subtypes expressed in NIH 3T3 cells. Compounds
      with a single methylene spacer in the side chain (7) have no agonist activity,
      but are weak antagonists in the Xenopus melanophore assay, irrespectively of the
      size or shape of the R substituent (R=CH(3) to c-C(4)H(7)). In contrast,
      compounds with two (8) or three (9) methylene spacers show partial agonist
      activity, though this does vary with the nature of the R substituent.
      Interestingly, the cyclopropane and cyclobutane R substituents, which are usually
      linked with antagonism, render the cyclopropanecarboxamido analog 9d and its
      cyclobutanecarboxamido congener 9e weak agonists. It seems, therefore, that in
      these compounds the R substituent constitutes a functional probe in the dynamic
      agonist-antagonist conformational equilibrium. One of the new molecules,
      antagonist 8c, exhibits a noteworthy MT(2) subtype selectivity (13-fold), whereas
      the acetamido analog 9a (with a three methylene units spacer) also acts as an
      antagonist and is the only analog exhibiting MT(1) selectivity (>10-fold). In
      contrast to the analogous N1-C7 annulated indole derivatives, recently reported,
      the new C1-C8 condensed isoquinolines are not all pure antagonists. Despite their
      modest receptor affinity at the binding site these compounds demonstrate that the
      nature of the response (agonist or antagonist activity) is dependent, in this
      case, on both the side chain spacer's length and the size and shape of the R
      group.

PMID- 17223161
TI  - Interest of RGD-containing linear or cyclic peptide targeted tetraphenylchlorin
      as novel photosensitizers for selective photodynamic activity.
AB  - Destruction of the neovasculature is essential for tumor eradication by
      photodynamic therapy. Since the over-expression of integrins is correlated with
      tumor angiogenesis, we conjugated a photosensitizer (5-(4-carboxyphenyl)-10,15,20
      triphenylchlorin or porphyrin) to the alpha(v)beta(3) integrin specific peptide
      RGD (H-Arg-Gly-Asp-OH) motif as a common sequence. We reported an efficient solid
      phase synthesis of a new family of peptidic photosensitizers with linear or
      cyclic[RGDfK] RGD motif and compared conjugates in vitro selectivity and
      photodynamic activity. The conjugates were characterized by (1)H NMR, MALDI, UV
      visible spectroscopy and singlet oxygen formation was performed. Chlorins
      containing linear and constrained RGD motif were incorporated up to 98- and 80
      fold more, respectively, than the unconjugated photosensitizer over a 24-h
      exposure in human umbilical vein endothelial cells (HUVEC) over-expressing
      alpha(v)beta(3) integrin. Peptidic moiety also led to a non-specific increased
      cellular uptake by murine mammary carcinoma cells (EMT-6), lacking RGD binding
      receptors. Survival measurements demonstrated that HUVEC were greatly sensitive
      to conjugates-mediated photodynamic therapy.

PMID- 17223162
TI  - Monitoring atmospheric pollutants in the biosphere reserve Wienerwald by a
      combined approach of biomonitoring methods and technical measurements.
AB  - In this study a combined approach of bioindication results correlated with an
      extensive set of data on air pollution and climate was used to assess the
      pollution status of the Man and Biosphere Reserve Wienerwald (Austria).
      Bryophytes served as impact indicators (via the Index of Atmospheric Purity
      method IAP) at 30 sites as well as accumulation monitors for airborne trace
      elements (Al, Pb, V, S, Zn, Fe, Cu, Cr, Ni, Co, Mo, Cd, As, Sb and 16 EPA-PAHs)
      at 10 sites within the reserve. The results of these bioindication methods were
      subsequently correlated with further pollution (NO(2), SO(2) and dust) and
      climate data (precipitation, temperature and humidity). The findings obtained
      clearly indicate the following: Bryophyte distribution is solely influenced by
      the status of air quality, without interference by climatic or site-related
      factors, which is in contrast to several previous investigations. IAP-values
      correlated significantly with NO(2) (0.553; P=0.004), SO(2) winter values (0.511;
      P=0.013) and PM10 (dust) (0.561; P=0.013). The results obtained via chemical
      analyses revealed a strong correlation with data derived from the IAP
      methodology. In terms of the overall air quality within the biosphere reserve
      Wienerwald, the north-eastern part appears to be the most affected one with a
      most likely pollution contribution emitted by the capital city Vienna,
      agriculture and neighbouring countries.

PMID- 17223163
TI  - Persistence and fate of 17beta-estradiol and testosterone in agricultural soils.
AB  - Steroidal hormones are constantly released into the environment by man-made and
      natural sources. The goal of this study was to examine the persistence and fate
      of 17beta-estradiol and testosterone, the two primary natural sex hormones.
      Incubation experiments were conducted under aerobic and anaerobic conditions
      using [4-(14)C]-radiolabeled 17beta-estradiol and testosterone. The results
      indicated that 6% of 17beta-estradiol and 63% of testosterone could be
      mineralized to (14)CO(2) in native soils under aerobic conditions. In native
      soils under anaerobic conditions, 2% of testosterone and no 17beta-estradiol was
      methanogenized to (14)CH(4). Essentially, no mineralization of either
      testosterone or 17beta-estradiol to (14)CO(2) occurred in autoclaved soils under
      aerobic or anaerobic condition. Results also indicated that 17beta-estradiol
      could be transformed to an unidentified polar compound through abiotic chemical
      processes; however, 17beta-estradiol was only oxidized to estrone via biological
      processes. The TLC results also indicated that testosterone was degraded, not by
      physical-chemical processes but by biological processes. Results also indicated
      that the assumed risks of estrogenic hormones in the environment might be over
      estimated due to the soil's humic substances, which can immobilize majority of
      estrogenic hormones, and thereby reduce their bioavailability and toxicity.

PMID- 17223164
TI  - High zinc concentrations reduce rooting capacity and alter metallothionein gene
      expression in white poplar (Populus alba L. cv. Villafranca).
AB  - Poplar is a good candidate for phytoremediation purposes because of its rapid
      growth, extensive root system, and ease of propagation and transformation;
      however its tolerance to heavy metals has not been fully investigated yet. In the
      present work, an in vitro model system with shoot cultures was used to
      investigate the tolerance to high concentrations of zinc (Zn) of a commercial
      clone (Villafranca) of Populus alba. Based on chlorophyll content (leaf
      chlorosis) and the rate of adventitious root formation from shoot cuttings as
      parameters of damage, 0.5-4mM zinc concentrations were all toxic albeit to
      different extents. Northern blot and reverse transcriptase (RT)-PCR analyses were
      used to examine the expression profiles of types 1, 2 and 3 PaMT genes in stems,
      leaves and roots of plants exposed to Zn treatments. In leaves, MT1 and MT3 mRNA
      levels were enhanced by Zn, while MT2 transcripts were not affected. The PaMT
      expression profiles were differentially affected by Zn in an organ-specific
      manner, and the relationship with Zn concentration and exposure time was rarely
      linear. The developmental and molecular data reveal that the in vitro model is a
      sensitive and reliable system to study heavy metal stress responses.

PMID- 17223165
TI  - N-Nitroso compounds produced in deer mouse (Peromyscus maniculatus) GI tracts
      following hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) exposure.
AB  - Given the potent carcinogenic effects of most N-nitroso compounds, the reductive
      transformation of the common explosive hexahydro-1,3,5-trinitro-1,3,5-triazine
      (RDX) to a group of N-nitroso derivatives, hexahydro-1-nitroso-3,5-dinitro-1,3,5
      triazine (MNX), hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine (DNX), and
      hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) in the environment have caused
      concerns among the general public. Questions are arising about whether the same
      transformations also occur in mammals, and if true, to what extent. This study
      investigated the N-nitroso derivatives production in the deer mouse GI tract
      following RDX administration. Findings verified that such transformations do
      occur in the mammalian GI tract at notable levels: the average MNX concentrations
      in deer mice stomach were 85 microg/kg and 1318 microg/kg for exposure to 10mg/kg
      and 100mg/kg diet, respectively. DNX in stomach were 217 microg/kg for the
      10mg/kg dose group and 498 microg/kg for the 100mg/kg dose group. Changes in
      other toxic endpoints including body weight gain, food consumption, organ weight,
      and behavior were also reported.

PMID- 17223166
TI  - Polychlorinated naphthalenes and coplanar polychlorinated biphenyls in tissues of
      harbor seals (Phoca vitulina) from the northern Gulf of Alaska.
AB  - Blubber, liver and kidney samples of harbor seals (Phoca vitulina) from the
      northern Gulf of Alaska were collected during 2000-2001 for the analysis of
      polychlorinated naphthalenes (PCNs) and coplanar polychlorinated biphenyls
      (CoplPCBs). On the lipid weight (lw) base, the total concentrations of PCNs
      (Sigma PCNs) ranged from 0.3 to 27 ng/g lw, and the total concentrations of
      CoplPCBs (Sigma CoplPCBs) were 3.6-546 ng/g lw in all the tissue samples. Di
      ortho PCBs and mono-ortho PCBs were dominant followed by non-ortho PCBs and PCNs.
      Sigma Mono-ortho PCBs and Sigma di-ortho PCBs in nursing seals were apparently
      lower than those in male adult seals, but Sigma PCNs and Sigma non-ortho PCBs in
      female adults were not significantly different from those in male adults.
      Differences in PCNs and CoplPCBs congener profiles in female and male adult seals
      are apparently related to their chemical structure and properties, animal's
      developmental stages and physiological conditions. A large quantity of mono-ortho
      and di-ortho PCBs might be transferred to newborns from the nursing seals during
      lactation, while non-ortho PCBs and PCNs were relatively accumulative in the
      mother seals. Sigma PCNs and Sigma CoplPCBs in the harbor seals correlated with
      ages, gender, body weight and blubber thickness, but the blubber Sigma PCNs and
      Sigma CoplPCBs in Kodiak Island and Southern Alaska Peninsula (KIAP) did not
      significantly differ from those in Prince William Sound (PWS). In addition to the
      new PCB data, this first report on PCN contamination in Alaskan harbor seal
      tissues is useful for the wildlife and ecosystem management and human health
      protection.

PMID- 17223167
TI  - Dioxin concentrations in sediments of the Baltic Sea--a survey of existing data.
AB  - Recent survey results for polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs, dioxins) in Baltic Sea sediments from Finland, Sweden and Denmark were
      merged with previously published Baltic Sea data. Regional distribution of
      concentration levels, differences in congener patterns, and temporal changes in
      sediment profiles were examined. One of the main objectives was to study if any
      major point sources for different PCDD/F congeners could be identified on a
      regional scale, based on sediment records. The survey confirmed the impact of
      chlorophenol production derived highly chlorinated PCDF-congeners on the total
      toxicity in sediments in the Gulf of Finland near the Kymijoki river estuary.
      Signatures of other point sources or combined point sources pertinent to specific
      industry branches or particular production processes (such as pulp bleaching,
      vinyl chloride production, thermal processes) may be discerned. However, the
      findings did not support any of the known point sources significantly influencing
      those congeners that are most abundant in Baltic herring and salmon. Instead,
      regional distributions in the Baltic Sea indicate that atmospheric deposition may
      act as a major source for those congeners and especially for 2,3,4,7,8-PeCDF.
      There were clear indications of declines in levels in sediment in some areas, but
      generally the levels of highly chlorinated PCDD/Fs on the northern coast of the
      Gulf of Finland were still high when compared with other areas of the Baltic Sea.
      Major areas with data gaps cover the south-eastern and eastern coastal regions of
      the Baltic Proper and the southern Gulf of Finland.

PMID- 17223168
TI  - AhR-mediated and antiestrogenic activity of humic substances.
AB  - Humic substances (HS) were for decades regarded as inert in the ecosystems with
      respect to their possible toxicity. However, HS have been recently shown to
      elicit various adverse effects generally attributed to xenobiotics. In our study,
      we used MVLN and H4IIE-luc cell lines stably transfected with luciferase gene
      under control of estrogen receptor (ER) and Ah receptor (AhR; receptor connected
      with so-called dioxin-like toxicity) for assessment of anti/estrogenic and AhR
      mediated effects of 12 commercially available humic substances. Out of those,
      five humic acids were shown to induce AhR-mediated activity with relative
      potencies related to TCDD 2.6 x 10(-8)-7.4 x 10(-8). Organic extracts of HS
      solutions also elicited high activities what means that lipophilic molecules are
      responsible for a great part of effect. However, relatively high activity
      remaining in extracted solution suggests also presence of polar AhR-agonists.
      Contribution of persistent organic compounds to the observed effects was ruled
      out by H(2)SO(4) treatment. Eight out of twelve HS elicited significant
      antiestrogenic effects with IC(50) ranging from 40 to 164 mg l(-1). The possible
      explanations of the antiestrogenic effect include sorption of 17-beta-estradiol
      (E2) on HS, changes in membrane permeability for E2 or another specific
      mechanism.

PMID- 17223169
TI  - Dioxins, dioxin-like PCBs and chloroorganic contaminants in herring, Clupea
      harengus, from different fishing grounds of the Baltic Sea.
AB  - The contaminant levels of dioxins, dioxin-like PCBs and a range of chloroorganic
      compounds have been determined in relation to various fishing grounds of the
      Baltic Sea. Sampling covered an area from the Skagerrak to the coast of Latvia.
      The data are compared with herring from fishing grounds in the North Sea and west
      of the British Isles. Also the temporal trend of the dioxin levels in the edible
      part of herring landed around the Island of Rugen is given from commercial
      samples collected between 1996 and 2004. A continuous increase of the dioxin
      concentrations was observed from west to east. Lowest concentrations of 0.199 ng
      WHO-PCDD/F-TEQ kg(-1)wet weight were found in herring fillets west of the British
      Isles. Highest level of 6.972 ng WHO-PCCD/F-TEQ kg(-1)w.w. was analysed in
      fillets off the coast of Latvia. Results showed also a spatial dependence of the
      WHO-TEQ ratio dioxins:dioxin-like PCBs and of the dioxin congener profile. Only
      the DDT group of various chloroorganic compounds determined, showed a dependence
      from the fishing ground. A clear temporal tendency could not be deduced from the
      data.

PMID- 17223170
TI  - Bioavailability of PCDD/F from contaminated soil in young Goettingen minipigs.
AB  - For the general population the intake of food of animal origin is the main route
      of human exposure to polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/F). Besides this the ingestion of contaminated soil might be an important
      exposure path for small children. For risk assessment the knowledge of the
      bioavailable fraction of soil bound contaminants is important. In a balance study
      with young Goettingen minipigs the oral bioavailability of PCDD/F from
      contaminated soil was estimated by determination of the retention of PCDD/F from
      soil in different organs and tissues. Relative bioavailability was estimated by
      comparing the retention from soil to the retention of PCDD/F in organs and
      tissues after oral administration of a PCDD/F mixture extracted from the same
      soil by solvent. The soil had a PCDD/F-contamination of 5.3 microg I-TEq/kg and
      originated from a former arable land that had been treated with sludge from the
      port of Hamburg some years ago. Two groups of each four animals were exposed
      daily for 28 days via their diet either to 0.5 g soil per kg body weight and day
      (2.63 ng I-TEq/(kg(bw).d)) or to a daily dose of 1.58 ng I-TEq/(kg(bw).d) given
      to the diet by solvent. Five unexposed animals were used as a control group.
      Liver, adipose tissue, muscle, brain and blood were analyzed for their PCDD/F
      content. Accumulation of PCDD/F from soil or solvent in comparison to control
      animals was only observed for congeners with 2378-chlorosubstitution and
      predominantly took place in the liver. Bioavailability of 2378-chlorosubstituted
      congeners was in the range of 0.64%-21.9% (mean: 10.1%) from soil and 2.8%-59.8%
      (mean: 31.5%) when administered by solvent. The soil matrix reduced the
      bioavailability by about 70%. Expressed as I-TEq only 13.8% of the PCDD/F
      contamination were bioavailable from soil. The relative bioavailability of 2378
      chlorosubstituted congeners from soil in relation to administration by solvent
      was in the range of 2%-42.2% (mean: 28.4%). When not considering the
      bioavailability, the risk by oral uptake of PCDD/F contaminated soil might be
      overestimated.

PMID- 17223171
TI  - Risk assessment of dioxins and dioxin-like PCBs in food--comments by the German
      Federal Environmental Agency.
AB  - Human health risk assessments for dioxins and dioxin-like PCBs (with the
      exception of the one by US-EPA) recommend health based exposure limits within the
      range of 1-4 pg WHO-TEQ/kg bw per day. As all humans are exposed to measurable
      levels of dioxins and related substances, the determination of the tolerated
      daily intake is a very significant decision and may influence limit values
      guiding risk reduction measures and target levels. The proposed TDI has to
      protect all human subpopulations. In the case of dioxin this is particularly
      important as the exposure of infants through breast-feeding may exceed the
      exposure of adults by one or two orders of magnitude. An overview of recently
      recommended limit values (WHO, SCF, JECFA) for PCDDs, PCDFs and dioxin-like PCBs
      using WHO-TEFs shows the common feature that the values were derived only from
      non carcinogenic endpoints. In November 2000 the Scientific Committee on Food of
      the European Commission published an 'Opinion of the SCF on the Risk Assessment
      of Dioxins and Dioxin-like PCBs in Food' [SCF, Scientific Committee on Food 2000.
      Opinion of the SCF on the risk assessment of dioxins and dioxin-like PCBs in
      food. European Commission, Brussels, Adopted on November 2000
      http://europa.eu.int/comm/food/fs/sc/scf/out78_en.pdf]. On the basis of this
      extensive review of data and experimental results the Committee recommended a
      temporary tolerable weekly intake (t-TWI) of 7 pg WHO-TEQ/kg bw. Only six months
      later the SCF carried out a re-evaluation of its t-TWI from November 2000. The
      reconsideration of 'pivotal studies' led to the situation that the re-assessment
      is now based only on rat studies which investigated only reproductive effects
      only on male offspring and, in addition, three of these studies are single dose
      studies at gestational day 15. Applying an overall uncertainty factor of 10 to
      the LOAEL derived estimated human daily intakes (EHDI) the SCF concluded that 14
      pg/kg bw per week should be considered as a tolerable intake for 2,3,7,8-TCDD.
      The SCF stated that on a body weight basis, the dioxin intake of breast-fed
      infants has been estimated to be one to two orders of magnitude higher than the
      average adult intake. Recent German data suggest that the body burden of formerly
      breast-fed children aged 9-11 is still about 30% higher than those of their
      formula-fed age-mates. As breast-feeding has measurable benefits for neurological
      and immunological development, formula feeding cannot be recommended as an
      alternative to lower dioxin intake. So the only remaining way to lower the dioxin
      uptake is to drastically reduce the background exposure of the general
      population. It is acknowledged that any recommendation of a precise number for a
      TDI is flawed by uncertainties and the possibility of different weight being
      given to the studies of relevance. The determination of the TDI has influence on
      all regulatory limit values that are based on the TDI value. A higher TDI lowers
      the level of protection for humans. It is proposed by the German Federal
      Environmental Agency that the TDI should be reassessed in a process transparent
      to the public and on the basis of all relevant endpoints from animal experiments
      and human epidemiology, including the assessment of cancer risks.

PMID- 17223172
TI  - Concentrations of polychlorinated dibenzo-p-dioxins in processed ball clay from
      the United States.
AB  - Processed ball clays commonly used by the ceramic art industry in the United
      States were collected from retail suppliers and analyzed for the presence and
      concentration of the 2,3,7,8-Cl substituted polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDDs/PCDFs). The average PCDD toxic equivalent (TEQ)
      concentrations of these processed ball clays was approximately 800 pg/g (TEQ-WHO)
      with characteristic congener profiles and isomer distributions similar to
      patterns of previously analyzed raw and processed ball clays. The PCDF
      concentrations were below the average limit of detection (LOD) of 0.5 pg/g.
      Correlation analyses reveal no significant relationship between total organic
      carbon (TOC) and either individual, homologues, and total tetra-through octa
      chlorinated PCDD congeners, or TEQ concentrations of the processed ball clays.
      The results are consistent with earlier studies on levels of PCDDs in ball clays.
      Data from earlier studies indicated that dioxins may be released to the
      environment during the processing of raw clay or the firing process used in
      commercial ceramic facilities. The presence of dioxin in the clays also raises
      concerns about potential occupational exposure for individuals involved in the
      mining/processing of ball clay, ceramics manufacturing and ceramic artwork.

PMID- 17223173
TI  - Human intake fractions of pesticides via greenhouse tomato consumption: comparing
      model estimates with measurements for Captan.
AB  - Human intake due to pesticide residues in food commodities can be much higher
      than those related to water consumption and air inhalation, stressing the
      importance to correctly estimate pesticide uptake into plants and predict
      subsequent intake by humans. We calculated the human intake fraction of captan
      via tomato consumption taking into account the time between pesticide application
      and harvest, the time between harvest and consumption, the absorption of spray
      deposit on plant surfaces, transfer properties through the cuticle, degradation
      inside the plant and loss due to food processing. Human population intake
      fractions due to ingestion were calculated for complete, washed and peeled
      tomatoes. The calculated intake fractions were compared with measurements derived
      from an experimental setup in a Mediterranean greenhouse. The fraction of captan
      applied in the greenhouse as plant treatment that eventually is ingested by the
      human population is on average 10(-2)-10(-5), depending on the time between
      pesticide application and ingestion of tomatoes and the processing step
      considered. Model and experimentally derived intake fractions deviated less than
      a factor of 2 for complete and washed tomatoes and a factor of 3 for peeled
      tomatoes. Intake fractions due to air inhalation and consumption of drinking
      water are expected to be significantly lower (5-9 orders of magnitude) than those
      induced by the intake of tomatoes in this case study.

PMID- 17223174
TI  - Pollution sources and occurrences of selected persistent organic pollutants
      (POPs) in sediments of the Mekong River delta, South Vietnam.
AB  - The Mekong River delta is one of the largest agricultural land in the Southeast
      Asia. It plays a very important role for agriculture and fisheries in South
      Vietnam. However, comprehensive studies on the environmental pollution of
      persistent organic pollutants (POPs) in Mekong River delta have not been carried
      out in recent years. In this study, we collected sediment samples from the Mekong
      River to evaluate the contamination and ecological risks caused by several POPs.
      The contamination pattern of POPs was DDT>PCBs>CHLs>HCHs>HCB. DDTs are the most
      abundant pollutants, their concentration ranging from 0.01 to 110 ng/g dry wt,
      followed by PCBs (0.039-9.2 ng/g dry wt). DDTs and PCBs concentrations were
      higher in sediment from adjacent to urban areas than those from rural and
      agricultural sites, suggesting urban areas as important point sources of DDTs and
      PCBs to the river. Ratio of p,p'-DDT/p,p'-DDE was lower compared to those
      previously reported. However, some samples still had the ratio higher than 0.5,
      indicating recent input of DDT into the aquatic environments. This result shows
      that although the magnitude of contamination decreased over time, recent inputs
      of DDTs to the river still occur. Some sediment samples had concentrations of DDT
      compounds higher than the standards from the Canadian Environmental Quality
      Guideline, suggesting continuous monitoring for POPs contamination in the Mekong
      River is necessary.

PMID- 17223175
TI  - Long-term effects of subcutaneously injected 2,3,7,8-tetrachlorodibenzo-p-dioxin
      on the liver of rhesus monkeys.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) accumulates and remains stable in the
      fatty tissues and liver of rodents for a long time. Considering the pronounced
      difference between species, long-term, low dose hepatic effects of TCDD were
      investigated after subcutaneous administration of TCDD into rhesus monkeys during
      pregnancy. Macroscopic and histopathological examination of the liver carried out
      4 y after TCDD administration demonstrated intrahepatic focal fatty changes,
      infarction, hemorrhage, microthrombi-formation, sinusoidal ectasia, small
      hepatocyte hyperplasia, and increased number of alpha-smooth muscle actin (alpha
      SMA)-positive cells. An electron microscopic study disclosed sinusoidal
      endothelial cell degeneration and injury in the liver of TCDD-treated monkeys.
      Western blot analysis showed downregulation of aryl hydrocarbon receptor (AhR)
      protein expression and decreased level of vascular endothelial (VE) cadherin but
      increased expression levels of CYP1A1 and transforming growth factor beta (TGF
      beta) protein in the liver tissues. These changes observed in TCDD-exposed
      monkeys indicated sinusoidal endothelial cell injury and impairment in
      intrasinusoidal microcirculation. Infarction, focal fatty change, and
      microthrombi-formation are considered to be closely associated with intrahepatic
      circulatory impairment. Increased number of alpha-SMA-positive cells and
      decreased level of VE cadherin expression in the liver tissues might also be
      associated with sinusoidal endothelial cell injury. In addition, downregulation
      of AhR expression and increased CYP1A1 protein levels in the liver were
      consistent with persistent effects of TCDD. Although it has been reported that
      TCDD induced endothelial cell injury, this is the first report to describe
      vascular disorders and protein expression in the liver after injection with TCDD
      in a primate model.

PMID- 17223176
TI  - Thermal degradation of 2-chlorophenol promoted by CuCl2 or CuCl: formation and
      destruction of PCDD/Fs.
AB  - The oxidative degradation of 2-chlorophenol in air (equivalence ratio phi=0.8)
      was investigated at 350 degrees C by using the sealed tube technique under
      different conditions: in the gas phase and in the presence of copper chlorides
      (CuCl2 and CuCl in different proportions). Not only PCDD/Fs but carbon oxides and
      other organic products such as chlorophenols, chlorobenzenes, tetrachloroethylene
      and tetrachlorocyclopentenedione were quantified in order to evaluate the
      relative importance of reaction pathways. Additional experiments were performed
      to analyse the degradation products of octachlorodibenzodioxin and 2
      monochlorodibenzodioxin. Although it was stated that chlorobenzenes could be
      formation precursors for PCDD/Fs, experimental data obtained in this work show
      that chlorobenzenes can also be degradation products of PCDD/Fs.

PMID- 17223177
TI  - Organochlorinated contaminants in decapod crustaceans from the coasts of Brittany
      and Normandy (France).
AB  - The contamination and distribution of organochlorinated compounds were considered
      in three crustacean species (edible crab, Cancer pagurus; spider crab, Maja
      brachydactyla; velvet swimming crab, Necora puber) from five sites along the
      coasts of Brittany and Normandy (Western and North-Western France). PCBs (16
      single congeners), pp'-DDE and HCB were measured in hepatopancreas, gonads and
      muscle: in all, 175 samples were analysed. The spider crab was the only species
      found in the five sampling sites, thus enabling comparison between areas.
      Specimens from Antifer were much more contaminated (summation operator 16 PCBs in
      hepatopancreas=2000-4000 ng g(-1) dry weight) than those from other sites (50
      1000 ng g(-1) d.w.). Among all the three species, the spider crab appeared more
      contaminated by PCBs than the edible crab, by a factor 2-3, probably in relation
      with specific differences in their life cycle. There was no difference due to the
      gender of the species. Within the different analysed tissues, contamination
      levels increased from muscle to gonads and hepatopancreas in relation with the
      fat content. A very similar PCB composition was observed in all samples, PCB
      fingerprints being characterised by the relative importance of the more
      persistent PCB congeners: CB153, 138, 180, 187, and 118. Finally, these results
      were compared to recent food regulations first of maximum marker PCB intake and
      secondly of maximum dioxin-like PCB intake. By considering the muscle, all
      samples were far below the regulatory limits; for hepatopancreas and gonads,
      however, some samples were unfit for human consumption.

PMID- 17223178
TI  - Disrupting effects of hydroxy-polychlorinated biphenyl (PCB) congeners on
      neuronal development of cerebellar Purkinje cells: a possible causal factor for
      developmental brain disorders?
AB  - Polychlorinated biphenyls (PCBs) and hydroxy-PCB (OH-PCB) metabolites are widely
      distributed bioaccumulative environmental chemicals and have similar chemical
      structures to those of thyroid hormones (THs). Previously, we reported that THs
      are essential for neuronal development and the low doses of two OH-PCBs, namely,
      4-OH-2',3,3',4',5'-pentachlorobiphenyl (4'-OH-PeCB-106) and 4-OH-2',3,3',4',5,5'
      hexachlorobiphenyl (4'-OH-HxCB-159), inhibited the TH-dependent dendritic
      development of Purkinje cells in mouse cerebellar cultures using serum-free
      defined medium. To determine which type of OH-PCBs affect neuronal development,
      we further examined several OH-PCBs and other estrogenic chemicals using this
      simple and sensitive assay system. Two-way ANOVA was used to assess the effects
      of OH-PCBs and other chemicals on both factors of their concentrations and
      with/without T4 in the assay of TH-dependent dendritic development of Purkinje
      cells. Aside from the two OH-PCBs, 4-OH-2',3,4',5,6'-pentachlorobiphenyl (4'-OH
      PeCB-121) and bisphenol A significantly inhibited the TH-dependent dendritic
      development of Purkinje cells, whereas 4-OH-2',3,3',5',6'-pentachlorobiphenyl (4'
      OH-PeCB-112), 4-OH-2',3,3',5,5',6'-hexachlorobiphenyl (4'-OH-HxCB-165), 4-OH
      2,2',3,4',5,5',6-heptachlorobiphenyl (4-OH-HpCB-187), progesterone and
      nonylphenol did not induce any inhibition, but significantly promoted the
      dendritic extension of Purkinje cells in the absence of THs. Other estrogenic
      chemicals, including beta-estradiol, diethyl stilbestrol and p-octylphenol did
      not show significant inhibitory or promoting effects. From these results, it is
      suggested that exposure to OH-PCBs and other environmental chemicals may disrupt
      normal neuronal development and cause some developmental brain disorders, such as
      LD, ADHD, and autism.

PMID- 17223179
TI  - Polychlorinated biphenyls and DDT in swordfish (Xiphias gladius) and blue shark
      (Prionace glauca) from Brazilian coast.
AB  - The polychlorinated biphenyls (PCBs) and DDT may bioaccumulate in the aquatic
      food web and have been of great concern due to their toxic effects on wildlife
      and human health. There is evidence showing that fish in the human diet
      contributes at a significant proportion to the total intake of PCBs and other
      organochlorine compounds, particularly fish with higher fat levels. This study
      investigated the concentration of PCBs and DDTs in muscle tissues of samples of
      the blue shark (Prionace glauca) and a swordfish (Xiphias gladius) from east
      Brazilian coast and estimate the human exposure to total DDTs through the
      consumption of both the species. Samples of the each species were caught between
      August and September 2001. The mean concentration for summation operator PCBs in
      P. glauca was 3.15 ng/g w.w. and the summation operator DDTs was 0.93 ng/g w.w.
      The mean concentration of summation operator PCBs in X. gladius was 6.50 ng/g and
      the mean of summation operator DDTs was 2.47 ng/g. The estimated daily intake of
      summation operator DDT through X. gladius or P. glauca consumption can be
      considered safe since it contributes to less than 0.1% of the limit of acceptable
      daily intake (ADI) of summation operator DDT proposed by WHO.

PMID- 17223180
TI  - Atrazine sorption and fate in a Ultisol from humid tropical Brazil.
AB  - This study combined laboratory based microcosm systems as well as field
      experiments to evaluate the mobility of atrazine on a Ultisol under humid
      tropical conditions in Brazil. Results from sorption experiments fit to the
      Freundlich isotherm model [K(f) 0.99 mg kg(-1)/(mg l(-1))(1/n)], and indicate a
      low sorption capacity for atrazine in this soil and consequently large potential
      for movement by leaching and runoff. Microcosm systems using (14)C-atrazine to
      trace the fate of the applied herbicide, showed that 0.33% of the atrazine was
      volatilized, 0.25% mineralized and 6.89% was recorded in the leachate. After 60 d
      in the microcosms, 75% of the (14)C remained in the upper 5 cm soil layer
      indicating atrazine or its metabolites remained close to the soil surface. In
      field experiments, after 60 d, only 5% of the atrazine applied was recovered in
      the upper soil layers. In the field experiments atrazine was detected at a depth
      of 50 cm indicating leaching. Simulating tropical rain in field experiments
      resulted in 2.1% loss of atrazine in runoff of which 0.5% was adsorbed onto
      transported soil particles and 1.6% was in solution. Atrazine runoff was greatest
      two days after herbicide application and decreased 10 fold after 15 d. The use of
      atrazine on Ultisols, in the humid tropics, constitutes a threat to water
      quality, causing surface water and ground water pollution.

PMID- 17223181
TI  - Vitellogenin and zona radiata proteins as biomarkers of endocrine disruption in
      peregrine falcon (Falco peregrinus).
AB  - The aim of this study was to test a specific method for the detection of
      Vitellogenin (Vtg) and Zona Radiata Proteins (Zrp) in plasma from peregrine
      falcon (Falco peregrinus) as specific biomarkers for the evaluation of the
      effects of endocrine disruptors. The method was assayed with different peregrine
      falcon individuals (including mature and immature birds of both sexes) from a
      Spanish population being studied in terms of their contamination with
      organochlorine compounds with endocrine disrupting properties. This study shows
      that mouse anti bird Vtg monoclonal antibody ND3C3 (Biosense) seems to be the
      most specific antibody in binding plasmatic lipoproteins in peregrine falcon when
      compared to other anti Vtg antibodies. Rabbit anti salmon Zrp polyclonal
      antibodies O146 (Biosense) show cross-reactivity with Zrp in the samples studied.
      These preliminary results confirm the applicability of both of these diagnostic
      tools assayed (induction of Vtg and Zrp) in detecting exposure to Endocrine
      Disrupting Chemicals (EDCs) in this species. The increase of Vtg and Zrp detected
      in male specimens suggest a potential hazard to EDCs in the peregrine falcon
      which represents a species still affected by organochlorine compounds, and in
      particular those with estrogenic activity.

PMID- 17223182
TI  - Ten years measuring PCDDs/PCDFs in ambient air in Catalonia (Spain).
AB  - This work summarizes the results of a ten year surveillance programme on PCDD/F
      in ambient air carried out in Catalonia (Spain). The study has been conducted by
      the Dioxin Laboratory of Spanish Council for Scientific Research (CSIC) in
      collaboration with the Environment Department of the Catalonian Government. 175
      samples have been collected throughout Catalonia from 1994 to 2004. Different
      sampling locations classified as industrial, traffic, urban, suburban and rural
      sites have been monitored in order to find the most contaminated zones as well as
      the ones with expected background concentrations. The highest concentrations
      found in this study were determined at the industrial locations. Concentrations
      ranging from 5 to 1196 fg I-TEQ/m3, with a mean value of 140 fg I-TEQ/m3 and from
      10 to 357 fg I-TEQ/m3, with a mean value of 72 fg I-TEQ/m3 were determined in
      industrial and traffic sampling points, respectively. In contrast, the lowest
      concentrations were found in rural stations, ranging from 5 to 45 fg I-TEQ/m3,
      with a mean value of 28 fg I-TEQ/m3. The PCDD/F concentration trend in Catalonian
      ambient air shown a clear drop of the median values occurred during the study
      sampling period. A decline of about 70% was observed from 1997-1998 to 2003-2004.

PMID- 17223183
TI  - Cumulative index of health disorders as an indicator of aging-associated
      processes in the elderly: results from analyses of the National Long Term Care
      Survey.
AB  - BACKGROUND: We employ an approach based on the elaborated frailty index (FI),
      which is capable of taking into account variables with mild effect on the aging,
      health and survival outcomes, and investigate the connections between the FI,
      chronological age and the aging-associated outcomes in the elderly. METHODS:
      Cross-sectional analysis of pooled data from the National Long Term Care Survey
      (NLTCS) assessing health and functioning of the U.S. elderly in 1982, 1984, 1989,
      1994, and 1999. RESULTS: Distributions of frequency, residual life span,
      mortality rate, and relative risk of death are remarkably similar over age and
      FI. Coefficients of correlation between FI and age are low both for males (0.127,
      p<.01) and females (0.221, p<.01). The FI-specific age patterns show deceleration
      at advanced ages. The FI can provide order of magnitude better resolution in
      estimating mean remaining life span compared to age. Males have smaller FI than
      females while males' mortality risks are higher. For short-time horizons, the FI
      and age are largely independently associated with mortality risks. CONCLUSIONS:
      The FI: (i) can be considered as an adequate sex-specific indicator of the aging
      associated processes in the elderly, (ii) can characterize these processes
      independently of age, and (iii) is a better characteristic of the aging phenotype
      than chronological age.

PMID- 17223184
TI  - High resolution profiles of thallium, manganese and iron assessed by DET and DGT
      techniques in riverine sediment pore waters.
AB  - High resolution profiles of Mn, Tl and Fe concentrations have been assessed in
      the pore waters of river Leie sediments at Warneton and Menen (at the border of
      Belgium and France) by DET (Diffusive Equilibrium in Thin Films) and DGT
      (Diffusive Gradients in Thin Films) techniques. The oxidized, solid Mn (IV), Tl
      (III) and Fe (III) compounds were reduced in the suboxic (+255 to -20 mV versus
      Standard Hydrogen Electrode (SHE)) riverine sediments and since these reduced
      species are much more soluble also they are released into the pore waters. The
      highest DET (total dissolved) concentrations of Fe (76 mg l(-1)), Mn (2 mg l(-1))
      were observed at the station of Menen, while Tl maxima differed only slightly
      between the 3 surveys (21 to 27 microg l(-1)). The average ratios of Fe/Mn/Tl in
      the pore waters at the 3 sampling stations are fairly constant for both the DET
      and DGT samplings. However, the results indicate that compared to Fe and Tl a
      greater proportion of the Mn measured by DET is accumulated by DGT, reflecting
      the ready supply of Mn from solid phase to solution.

PMID- 17223185
TI  - Characterisation of microbial biocoenosis in vertical subsurface flow constructed
      wetlands.
AB  - In this study a quantitative description of the microbial biocoenosis in
      subsurface vertical flow constructed wetlands fed with municipal wastewater was
      carried out. Three different methods (substrate induced respiration, ATP
      measurement and fumigation-extraction) were applied to measure the microbial
      biomass at different depths of planted and unplanted systems. Additionally,
      bacterial biomass was determined by epifluorescence microscopy and productivity
      was measured via (14)C leucine incorporation into bacterial biomass. All methods
      showed that >50% of microbial biomass and bacterial activity could be found in
      the first cm and about 95% in the first 10 cm of the filter layer. Bacterial
      biomass in the first 10 cm of the filter body accounted only for 16-19% of the
      total microbial biomass. Whether fungi or methodical uncertainties are mainly
      responsible for the difference between microbial and bacterial biomass remains to
      be examined. A comparison between the purification performance of planted and
      unplanted pilot-scale subsurface vertical flow constructed wetlands (PSCWs)
      showed no significant difference with the exception of the reduction of
      enterococci. The microbial biomass in all depths of the filter body was also not
      different in planted and unplanted systems. Compared with data from soils the
      microbial biomass in the PSCWs was high, although the specific surface area of
      the used sandy filter material available for biofilm growth was lower, especially
      in the beginning of the set-up of the PSCWs, due to missing clay and silt
      fraction.

PMID- 17223186
TI  - Amino acid levels in some brain areas of inducible nitric oxide synthase knock
      out mouse (iNOS-/-) before and after pentylenetetrazole kindling.
AB  - Inducible nitric oxide synthase knock-out (iNOS(-/-)) mice are valid models of
      investigation for the role of iNOS in patho-physiological conditions. There are
      no available data concerning neuroactive amino acid levels of iNOS(-/-) mice and
      their behaviour in response to pentylenetetrazole (PTZ). We found no significant
      differences in the convulsive dose 50 (CD(50)) between iNOS(-/-) and control
      (iNOS(+/+)) mice, however, iNOS(-/-) mice reach the kindled status more slowly
      than control, suggesting that in basal condition the GABA-benzodiazepine
      inhibitory inputs are unaltered by iNOS mutation. Clear differences between
      iNOS(+/+) and iNOS(-/-) mice amino acid concentrations were evident both in basal
      conditions and after kindling. Our results show that aspartate was significantly
      lower in all brain areas studied except the brain stem whereas glutamate and
      glutamine were significantly higher in the cortex, hippocampus and brain stem.
      GABA was slightly and not significantly higher in the cortex, hippocampus and
      brain stem, whereas taurine was significantly higher in all areas except
      diencephalon and glycine was significantly lower in the diencephalon and
      cerebellum. In this context, the inability of iNOS(-/-) mice to increase the NO
      levels following PTZ administrations indicate that NO might play a pro
      epileptogenic role in the genesis and development of some types of epilepsy.
      Since there is no correlation between neurotransmitter levels and the development
      of kindling, it is possible to exclude that the difference between the two
      strains is due to an imbalance between the considered neurotransmitters, and it
      is then possible that this difference is due to the presence of iNOS, which might
      be involved in long term plasticity of the brain.

PMID- 17223187
TI  - Effects of intracerebroventricularly-injected morphine on anxiety, memory
      retrieval and locomotor activity in rats: involvement of vasopressinergic system
      and nitric oxide pathway.
AB  - Morphine has been shown to alter several behavioural processes. We aimed to
      investigate the effects of intracerebroventricular (i.c.v.) morphine on anxiety,
      memory retrieval and locomotor activity in rats and to elucidate the possible
      involvement of the vasopressinergic system and the nitric oxide (NO) pathway in
      these effects. Rats were pretreated with morphine (0.5, 5, 50 microg/5 microl;
      i.c.v.) or saline (5 microl; i.c.v.) 30 min before the elevated plus maze test,
      the probe trial of the Morris water maze and the open field test. Morphine (5
      microg/5 microl; i.c.v.) induced significant anxiolytic effects in the elevated
      plus maze. None of the doses of morphine produced any effects in the probe trial
      of the Morris water maze and the open field. Pretreatment with an arginine
      vasopressin (AVP) V(1) receptor antagonist (25, 125 ng/5 microl; i.c.v.), an AVP
      V(2) receptor antagonist (25, 125 ng/5 microl; i.c.v.), or L-NAME, an NO synthase
      inhibitor (5, 25 microg/5 microl; i.c.v.) 30 min before morphine significantly
      prevented the anxiolytic effects of morphine. These results suggest that i.c.v.
      morphine has significant anxiolytic effects, probably mediated by both
      vasopressinergic system and NO pathway, but has no effect on memory retrieval or
      locomotor activity, at least at the applied doses.

PMID- 17223188
TI  - Involuntary language switching in two bilingual patients during the Wada test and
      intraoperative electrocortical stimulation.
AB  - We present two bilingual patients without language disorders in whom involuntary
      language switching was induced. The first patient switched from Dutch to English
      during a left-sided amobarbital (Wada) test. Functional magnetic resonance
      imaging yielded a predominantly left-sided language distribution similar for both
      languages. The second patient switched from French to Chinese during
      intraoperative electrocortical stimulation of the left inferior frontal gyrus. We
      conclude that the observed language switching in both cases was not likely the
      result of a selective inhibition of one language, but the result of a temporary
      disruption of brain areas that are involved in language switching. These data
      complement the few lesion studies on (involuntary or unintentional) language
      switching, and add to the functional neuroimaging studies of switching,
      monitoring, and controlling the language in use.

PMID- 17223189
TI  - Episodic and semantic memory influences on picture naming in Alzheimer's disease.
AB  - This study investigated the relationship between semantic and episodic memory as
      they support lexical access by healthy younger and older adults and individuals
      with Alzheimer's disease (AD). In particular, we were interested in examining the
      pattern of semantic and episodic memory declines in AD (i.e., word-finding
      difficulty and impaired recent memory) vis-a-vis more preserved remote memories.
      We administered a picture naming task in which the episodic period of the
      pictures and whether the pictured items were unique to one period or commonly
      used across periods were varied. Groups of younger adults (N=40), healthy older
      adults (N=20) and older adults with AD (N=18) were asked to name drawings of
      objects in four conditions: dated unique, contemporary unique, dated common, and
      contemporary common. The results indicated that all participants named items that
      were common to both episodic periods more successfully than items unique to one
      period. An interaction was observed such that the healthy older and AD groups
      were more successful in retrieving names of objects presented in the dated
      compared to contemporary unique conditions, whereas the younger adults showed the
      reverse pattern. These results indicate that naming ability is affected both by
      the cumulative frequency of using an item over a lifetime and by when an item was
      first acquired. The findings support a theoretical stance which proposes an
      enduring reciprocal link between semantic and episodic memory. This theoretical
      relationship has practical implications for the development of intervention
      strategies when interacting with persons who have AD.

PMID- 17223190
TI  - Multivariate strategies in functional magnetic resonance imaging.
AB  - We discuss aspects of multivariate fMRI modeling, including the statistical
      evaluation of multivariate models and means for dimensional reduction. In a case
      study we analyze linear and non-linear dimensional reduction tools in the context
      of a 'mind reading' predictive multivariate fMRI model.

PMID- 17223191
TI  - Self-assembled molecular magnets on patterned silicon substrates: bridging bio
      molecules with nanoelectronics.
AB  - The paper reports the methods of preparing molecular magnets and patterning of
      the molecules on a semiconductor surface. A highly magnetically aligned
      metallothionein containing Mn and Cd (Mn,Cd-MT-2) is first synthesized, and the
      molecules are then placed into nanopores prepared on silicon (001) surfaces using
      electron beam lithography and reactive ion-etching techniques. We have observed
      the self-assemble growth of the MT molecules on the patterned Si surface such
      that the MT molecules have grown into rod or ring type three-dimensional
      nanostructures, depending on the patterned nanostructures on the surface. We also
      provide scanning electron microscopy, atomic force microscopy, and magnetic force
      microscope studies of the molecular nanostructures. This engineered molecule
      shows molecular magnetization and is biocompatible with conventional
      semiconductors. These features make Mn,Cd-MT-2 a good candidate for biological
      applications and sensing sources of new nanodevices. Using molecular self
      assembly and topographical patterning of the semiconductor substrate, we can
      close the gap between bio-molecules and nanoelectronics built into the
      semiconductor chip.

PMID- 17223192
TI  - Heavy metal toxicity in Exosphaeroma gigas (Crustacea, Isopoda) from the coastal
      zone of Beagle Channel.
AB  - Acute toxicity of copper, cadmium, and zinc on isopod Exosphaeroma gigas was
      evaluated at 20 per thousand and 30 per thousand salinity. Six concentrations
      were assayed to estimate effective concentration of the toxicant that affects 50%
      of tested animal (EC50), while physiological responses and bioaccumulation were
      determined at 0.42 and 1.95 mg L(-1) of each metal. The following toxicity orders
      were obtained: Cd>or=Cu>Zn at 20 per thousand salinity and Cu>Zn>or=Cd at 30 per
      thousand salinity. Copper treatments showed a reduction in oxygen consumption at
      30 per thousand salinity, while an opposite trend was observed at 20 per thousand
      salinity. Zinc caused dissimilar effects, while in cadmium significant reduction
      was only registered in 0.42(20 per thousand) mg L(-1). Ammonia excretion was
      generally higher in treatments than control at 20 per thousand salinity. At 30
      per thousand salinity, excretion did not change in relation to control or
      diminished. In general terms, O:N atomic ratios indicated a preponderant protein
      metabolism. Bioaccumulation of assayed metals was higher at lowest salinity and
      increased with increasing toxic concentrations.

PMID- 17223193
TI  - The use of Chironomus riparius larvae to assess effects of pesticides from rice
      fields in adjacent freshwater ecosystems.
AB  - A bioassay with Chironomus riparius larvae, using larval development and growth
      as endpoints, was carried out inside a rice field and in the adjacent wetland
      channel in Portugal, during pesticide treatments (molinate, endosulfan and
      propanil) to determine impact caused by pesticide contamination in freshwater
      ecosystems. The bioassay was also performed under laboratory conditions, to
      assess whether in situ and laboratory bioassays demonstrated comparable results.
      Growth was inhibited by concentrations of endosulfan (2.3 and 1.9 microgL(-1)
      averages) in water from rice field in both the field and laboratory, and by
      concentrations of endosulfan (0.55 and 0.76 microgL(-1) averages) in water from
      the wetland channel in the laboratory bioassay, while development was not
      affected. C. riparius larvae were not affected by molinate and propanil
      concentrations. The results indicate that endosulfan treatments in rice fields
      may cause an ecological impairment in adjacent freshwater ecosystems. The results
      also indicate that laboratory testing can be used to assess in situ toxicity
      caused by pesticide contamination.

PMID- 17223194
TI  - Neurofunctional correlates of vulnerability to psychosis: a systematic review and
      meta-analysis.
AB  - An understanding of the neurobiological correlates of vulnerability to psychosis
      is fundamental to research on schizophrenia. We systematically reviewed data from
      studies published from 1992 to 2006 on the neurocognitive correlates (as measured
      by fMRI) of increased vulnerability to psychosis. We also conducted a meta
      analysis of abnormalities of activation in the prefrontal cortex (PFC) in high
      risk and first episode subjects, and reviewed neuroimaging studies of high-risk
      subjects that used PET, SPECT and MRS. Twenty-four original fMRI papers were
      identified, most of which involved tasks that engaged the PFC. In fMRI studies,
      vulnerability to psychosis was associated with medium to large effect sizes when
      prefrontal activation was contrasted with that in controls. Relatives of patients
      affected with psychosis, the co-twins of patients and subjects with an At Risk
      Mental State (ARMS) appear to share similar neurocognitive abnormalities.
      Furthermore, these are qualitatively similar but less severe than those observed
      in the first episode of illness. These abnormalities have mainly been described
      in the prefrontal and anterior cingulated cortex, the basal ganglia, hippocampus
      and cerebellum.

PMID- 17223195
TI  - Aquatic toxicity of acetaminophen, carbamazepine, cimetidine, diltiazem and six
      major sulfonamides, and their potential ecological risks in Korea.
AB  - Pharmaceuticals are manufactured and used for specific biological functions in
      veterinary and human medicine. Their detection in the environment and their
      bioactivity have resulted in concern for potential adverse effects on non-target
      species. Notwithstanding recent attention for their occurrence in the
      environment, there are significant research gaps for existing pharmaceuticals
      with regard to their potential ecological consequences. In this study, the four
      most abundantly used pharmaceuticals in Korea, namely acetaminophen,
      carbamazepine, cimetidine, and diltiazem, and six sulfonamide related
      antibiotics, including sulfamethoxazole, sulfachlorpyridazine, sulfathiazole,
      sulfamethazine, sulfadimethoxine, and trimethoprim were examined for their acute
      aquatic toxicity employing a marine bacterium (Vibrio fischeri), a freshwater
      invertebrate (Daphnia magna), and the Japanese medaka fish (Oryzias latipes). In
      general, Daphnia was the most susceptible among the test organisms. The most
      acutely toxic among the chemicals tested in this study was diltiazem, with a
      median lethal concentration of 8.2 mg/L for D. magna. The resulting acute
      toxicity of these pharmaceuticals was reasonably predicted by physicochemical
      descriptors such as pH-dependent distribution coefficient and EHOMO-ELUMO gap.
      Predicted environmental concentrations (PECs) derived for the test
      pharmaceuticals in Korea ranged between 0.14 and 16.5 microg/L. Hazard quotients
      derived from PECs and predicted no effect concentrations (PNECs) for
      sulfamethoxazole and acetaminophen were 6.3 and 1.8, respectively, suggesting
      potential environmental concerns and a need for further investigation.

PMID- 17223196
TI  - Triptolide impairs dendritic cell migration by inhibiting CCR7 and COX-2
      expression through PI3-K/Akt and NF-kappaB pathways.
AB  - Inhibition of dendritic cell (DC) migration into tissues and secondary lymphoid
      organs is an efficient way to induce immunosuppression and tolerance. CCR7 and
      PGE(2) are critical for DC migration to secondary lymphoid organs where DC
      initiate immune response. Triptolide, an active component purified from the
      medicinal plant Tripterygium Wilfordii Hook F., is a potent immunosuppressive
      drug capable of prolonging allograft survival in organ transplantation by
      inhibiting T cell activation and proliferation. Considering the essential role in
      T cell tolerance of DC migration to secondary lymphoid organs, here we
      demonstrate that triptolide can significantly inhibit LPS-triggered upregulation
      of CCR7 expression and PGE(2) production by inhibiting cyclooxygenase-2 (COX-2)
      expression in DC, thus impairing DC migration towards CCR7 ligand CCL19/MIP
      3betain vitro. Moreover, triptolide-treated DC display impaired migration into
      secondary lymphoid organs and in vivo administration of triptolide also inhibits
      DC migration. Further studies show that the triptolide-mediated inhibitory
      effects of LPS-induced activation of phosphatidylinositol-3 kinase (PI3-K)/Akt
      and nuclear NF-kappaB activation are involved in down-regulation of COX-2 and
      CCR7 expression resulting in impaired migration to secondary lymphoid organs of
      DC. Therefore, inhibition of DC migration through decreasing COX-2 and CCR7
      expression via PI3-K/Akt and NF-kappaB signal pathways provides additional
      mechanistic explanation for triptolide's immunosuppressive effect.

PMID- 17223197
TI  - Platinum(II) complexes with l-methionylglycine and l-methionyl-l-leucine ligands:
      synthesis, characterization and in vitro antitumoral activity.
AB  - Four dipeptide complexes of the type [PtX(2)(dipeptide)] x H(2)O (X=Cl, I,
      dipeptide=l-methionylglycine, l-methionyl-l-leucine) were prepared. The complexes
      were characterized by (1)H, (13)C, (195)Pt NMR and infrared spectroscopy, DTG and
      elemental analysis. From the infrared, (1)H and (13)C NMR spectroscopy it was
      concluded that dipeptides coordinate bidentately via sulfur and amine nitrogen
      donor atoms. Confirmed with (13)C and (195)Pt NMR spectroscopy, each of the
      complexes exists in two diastereoisomeric forms, which are related by inversion
      of configuration at the sulfur atom. The (1)H NMR spectrum for the platinum(II)
      complex with l-methionylglycine and chloro ligands exhibited reversible,
      intramolecular inversion of configuration at the S atom; DeltaG( not equal)=72 kJ
      mol(-1) at coalescence temperature 349 K was calculated. In vitro cytotoxicity
      studies using the human tumor cell lines liposarcoma, lung carcinoma A549 and
      melanoma 518A2 revealed considerable activity of the platinum(II) complex with l
      methionylglycine and chloro ligands. Further in vitro cytotoxic evaluation using
      human testicular germ cell tumor cell lines 1411HP and H12.1 and colon carcinoma
      cell line DLD-1 showed moderate cytotoxic activity for all platinum(II) complexes
      only in the cisplatin-sensitive cell line H12.1. Platinum uptake studies using
      atomic absorption spectroscopy indicated no relationship between uptake and
      activity. Potential antitumoral activity of this class of platinum(II) complexes
      is dependent on the kind of ligands as well as on tumor cell type.

PMID- 17223199
TI  - Exploring the margins of the bipolar spectrum: temperamental features of the
      typus melancholicus.
AB  - BACKGROUND: Both the melancholic type of personality (TM) and the concept of
      temperament offer promising insights for the phenotypic characterization of mood
      spectrum vulnerability. This research challenges the theoretical hiatus between
      the two psychopathological paradigms--the phenomenological and the neo
      Kraepelinian--by means of an empirically-based approach. METHOD: Temperamental
      features were assessed through the Semi-structured Affective Temperament
      Interview (TEMPS-I) in an outpatient population of 116 clinically stable,
      euthymic subjects who suffered from a DSM IV major depressive disorder,
      previously enrolled for a study on the characteristics of major/unipolar
      depressive episode. The sample was subsequently evaluated and dichotomized
      according to the Criteria for Typus Melancholicus (CTM). RESULTS: The TM subjects
      exhibited statistically significant differences in the temperamental profile as
      compared to non-TMs (NTM). A specific association between TM and hyperthymic
      temperament (HT) was confirmed by binary logistic regression analysis, suggesting
      that the phenomenological distinction TM vs. NTM is supported by different
      predisposing Kraepelinian "fundamental states". LIMITATION AND CONCLUSIONS:
      Although it is uncertain whether the findings would generalize outside the
      Italian culture, they nonetheless delineate a strong aggregation between TM and
      hyperthymic temperament, indicating that (1) an integrative neo
      Kraepelinian/phenomenological cooperative model is warranted to tap the
      complexity of the phenotypic diathesis for mood-disorders, and (2) the
      hyperthymic-melancholic type of personality rests on the margins of the bipolar
      spectrum. The main limitation of this study is that it enrolled a selected
      outpatient volunteer sample. A large scale study in general population is needed
      to confirm the hypothesis of a strong link between TM and HT and to shed light on
      the causes and meanings of this association.

PMID- 17223200
TI  - The sales of antidepressants and suicide rates in Norway and its counties 1980
      2004.
AB  - BACKGROUND: Suicide is a major public health problem and depression is among the
      most important risk factors for suicide. Treatment of depression might prevent
      suicide. To study this hypothesis further we conducted an ecological study.
      METHODS: An ecological study using sales data for antidepressants and numbers of
      suicides in Norway and Norwegian counties 1980-2004 was performed. Data on
      alcohol consumption and unemployment rates were registered and taken into
      account. Data were analyzed using Cochrane-Orcutt time series for the country as
      a whole. The county specific data were analyzed with a random coefficient model
      with county as subject and intercept and time (slope) as random variables using
      an unstructured covariance matrix. RESULTS: Sales of non-tricyclic
      antidepressants (non-TCAs) and suicide were clearly negatively related, even when
      controlling for alcohol and unemployment (adjusted r(2): 0.57). There was an
      effect modification between time and level of sales of non-TCAs. Studying the
      relationship between the sales of non-TCAs and the suicide rate, we found that it
      was significant and stronger for the low sales figures, but non-existent for the
      high sales figures. LIMITATIONS: Ecological studies cannot infer causality.
      CONCLUSIONS: The fall in suicide rates in Norway and its counties was related to
      the increased sales of non-TCAs. The effect was mostly a result of a sales
      increase in the lower sales segment, indicating that a change from the more toxic
      TCAs, or heightened awareness of depression and its treatment, could explain the
      relationship found between sales of newer antidepressants and a decrease in
      suicide rate.

PMID- 17223198
TI  - Neuroimmunopathology in a murine model of neuropsychiatric lupus.
AB  - Animal models are extremely useful tools in defining pathogenesis and treatment
      of human disease. For many years researchers believed that structural damage to
      the brain of neuropsychiatric (NP) patients lead to abnormal mental function, but
      this possibility was not extensively explored until recently. Imaging studies of
      NP-systemic lupus erythematosus (SLE) support the notion that brain cell death
      accounts for the emergence of neurologic and psychiatric symptoms, and evidence
      suggests that it is an autoimmunity-induced brain disorder characterized by
      profound metabolic alterations and progressive neuronal loss. While there are a
      number of murine models of SLE, this article reviews recent literature on the
      immunological connections to neurodegeneration and behavioral dysfunction in the
      Fas-deficient MRL model of NP-SLE. Probable links between spontaneous peripheral
      immune activation, the subsequent central autoimmune/inflammatory responses in
      MRL/MpJ-Tnfrsf6(lpr) (MRL-lpr) mice and the sequential mode of events leading to
      Fas-independent neurodegenerative autoimmune-induced encephalitis will be
      reviewed. The role of hormones, alternative mechanisms of cell death, the impact
      of central dopaminergic degeneration on behavior, and germinal layer lesions on
      developmental/regenerative capacity of MRL-lpr brains will also be explored. This
      model can provide direction for future therapeutic interventions in patients with
      this complex neuroimmunological syndrome.

PMID- 17223201
TI  - Lymphocytes upregulate signal sequence-encoding proopiomelanocortin mRNA and beta
      endorphin during painful inflammation in vivo.
AB  - Proopiomelanocortin (POMC)-derived beta-endorphin1-31 (END) released from immune
      cells inhibits inflammatory pain. We examined the expression of END and POMC mRNA
      encoding the signal sequence required for entry of the nascent polypeptide into
      the regulated secretory pathway in lymphocytes of rats with inflamed hindpaws.
      Within 12 h of inflammation, END increased in popliteal lymph nodes and at 96 h
      the intraplantar neutralization of END exacerbated pain. Lymphocytes expressed
      POMC, END, and full-length POMC mRNA. Semi-nested PCR revealed 8-fold increased
      exon 2-3 spanning POMC mRNA. Thus, painful inflammation enhances signal sequence
      encoding lymphocytic POMC mRNA needed for regulated secretion of functionally
      active END.

PMID- 17223203
TI  - Real-time RT-PCR (TaqMan) assays for the detection of Grapevine Leafroll
      associated viruses 1-5 and 9.
AB  - Real-time RT-PCR (TaqMan) assays were developed for the specific detection of
      Grapevine Leafroll associated viruses 1-5 and 9 (GLRaV-1-5 and -9). The assays
      were evaluated against a wide range of geographically distributed isolates.
      Geographical locations included South Africa, Europe, Australia, Asia, Latin
      America and the United States. Sequences were piled up from the most conserved
      regions of these geographically diverse isolates and TaqMan primers and probes
      were designed, targeting the regions with 100% sequence identity. Improving the
      RNA extraction technique and testing the quality of the RNA using the 18S
      ribosomal RNA TaqMan assay as an RNA specific internal control to validate the
      quality of the extracted RNA proved to generate better diagnostic assays. The
      real-time TaqMan RT-PCR assays were compared to the conventional RT-PCR assays
      for the detection of viruses using purified total RNA as well as crude extract.
      The data showed that when using total RNA extracted either by the Qiagen RNeasy
      method or by an ABI automated system more isolates were detected in comparison to
      crude extract. The optimum volume of crude extract prepared in GES for use in
      real-time TaqMan RT-PCR cocktail was determined to be 1 microl per reaction. In
      addition this report showed that TaqMan RT-PCR was more sensitive than
      conventional one-step RT-PCR for testing different isolates of these viruses
      either using RNA or crude tissue extract.

PMID- 17223202
TI  - A sensitive one-step real-time RT-PCR method for detecting Grapevine leafroll
      associated virus 2 variants in grapevine.
AB  - Grapevine leafroll syndrome is caused by a complex of up to nine different
      Grapevine leafroll-associated viruses (GLRaV-1-9) with GLRaV-2 being reported as
      one of the most variable species of this group. Many methods, including indexing,
      serological and molecular procedures, have been developed for the detection of
      GLRaV-2. However, due to the low concentration of the virus in plants and the
      high variability of GLRaV-2, a method with improved sensitivity and with the
      capacity to detect of all known variants is required. Such improvement is
      essential for grapevine rootstocks, as these are suspected to harbour frequent
      GLRaV-2 infections difficult to detect, thus contributing to the spread of the
      leafroll disease. The development of new universal primers is described using a
      target sequence located in the 3' end of the virus genome. These primers were
      combined with a one-step SYBR Green real-time RT-PCR assay to achieve
      quantitative detection. All 43 GLRaV-2 isolates tested in this study were
      identified readily and reproducibly, regardless of their geographical origin or
      variety of grapevine. Using the procedure developed in this study, the
      sensitivity was increased 125 times compared to a conventional single-tube RT
      PCR. This real-time method opens new perspectives for the sanitary selection of
      grapevine and in leafroll 2 disease monitoring.

PMID- 17223204
TI  - Correlation between breakdown of the blood-brain barrier and disease outcome of
      viral encephalitis in mice.
AB  - Changes in the permeability of the blood-brain barrier (BBB) were evaluated in
      two mouse models of viral encephalitis. The ability of sodium fluorescein (NaFl)
      to cross the BBB from the serum into the central nervous system was assayed in
      animals inoculated with virulent strains of either Banzi or Semliki Forest
      viruses. To test the hypothesis that increases in BBB permeability were
      associated with poor disease outcome subsequent experiments measured BBB
      permeability in conjunction with treatment with the interferon inducer Ampligen
      (poly I:poly C(12)U). A single intraperitoneal injection of Ampligen (1 mg/kg)
      administered either 24 h or 4-6 h before, but not 24 h after, virus inoculation
      with Banzi virus provided significant improvements in survival, viral brain
      titers, weight change and BBB permeability. In comparison, a similar treatment
      with Ampligen administered either 24 h or 4-6 h before inoculation with Semliki
      Forest virus was able to significantly improve weight change, and BBB
      permeability, but only animals receiving Ampligen 4-6 h pre-virus showed a
      significantly improved mortality. In general, it was found that evaluation of BBB
      permeability was a more sensitive indicator of disease outcome and the antiviral
      efficacy Ampligen than either weight change or brain viral titers.

PMID- 17223205
TI  - A new test for long-term spatial memory using an operant chamber in mice.
AB  - As part of ongoing efforts to develop fully automated and standardized behavioral
      tasks to probe cognitive and mnemonic capabilities of mice, we have constructed a
      new rectangular operant chamber. The chamber contains numerous nose poke holes,
      distributed over three of its inner walls that are identifiable by their spatial
      locations. Using this apparatus, we have developed a 'spatial' memory task using
      a successive reversal discrimination paradigm. Mice learn to discriminate, by
      trial and error, the position of a single valid hole during a Presentation
      session wherein they obtained a maximum of 20 reinforcements or 15 min time
      elapsed. Following a delay interval, they were resubmitted to the same task
      (Test) using the same reinforced hole. Results indicated that C57BL/6 mice
      exhibited a significant improvement during the Test, the magnitude of the
      improvement (memory savings) being dependent on the length of retention intervals
      ranging from 5 min to 24h. In addition, discrimination performance was sensitive
      to scopolamine in a dose dependent manner. The simplicity in task set up and the
      minimal labor and space requirements make this task suitable for high throughput
      behavioral characterization of genetically modified mice.

PMID- 17223206
TI  - Early behavioural enrichment in the form of handling renders mouse pups
      unresponsive to anxiolytic drugs and increases NGF levels in the hippocampus.
AB  - Early life experiences, such as early handling, can influence neural development
      of rodents leading to changes in physiological and behavioural reactivity to
      stress. These effects are likely to be mediated by changes in maternal behaviour.
      This study analyzed the effects of different manipulations of the rearing
      environment on maternal behaviour and the behavioural and physiological response
      to mild challenges in CD-1 mouse pups early during development. Litters underwent
      either 15 min of neonatal handling (H) or were exposed briefly to an unfamiliar
      male intruder from postnatal (PND) days 2 to 14 (MI). Both groups were compared
      with litters which were not manipulated (NH). Compared to NH subjects, licking
      behaviour in the MI group was increased only on the first day of introduction of
      the male intruder, while the H group showed an increase in maternal behaviour on
      PND 10. On PND 8, pups ultrasonic vocalizations were recorded upon treatment with
      an anxiolytic drug (chlordiazepoxide 0, 2, or 7.5mg/kg). Results indicate that,
      although there were no differences among the groups when mice were injected with
      vehicle, handled subjects did not reduce their calling rate following drug
      administration, in contrast to the NH and MI groups. Following maternal
      separation and novelty exposure on PND 9, levels of hippocampal NGF increased
      significantly only in the H group. These data suggest that active pup
      manipulations in the form of handling favour behavioural and neural plasticity
      resulting in the maintenance of a high level of arousal and in increased
      neurotrophin levels in response to an acute manipulation. Changes in hippocampal
      levels of NGF might be involved in the appraisal of subtle changes in the early
      social environment.

PMID- 17223208
TI  - Participation of the inducible nitric oxide synthase on atrial natriuretic
      peptide plasma concentration during endotoxemic shock.
AB  - Atrial natriuretic peptide (ANP) is a hormone secreted in response to atrial or
      ventricular volume expansion and pressure overload, respectively. However, it has
      been found in studies with animals and patients an increase in ANP plasma
      concentration, during advanced septic shock, despite the fall in mean arterial
      pressure (MAP). Several studies support the hypothesis that NO may be involved in
      the regulation of ANP release. Since NO may have an effect on ANP release, we
      hypothesized that NO pathway may participate in the control of the ANP release
      induced by the endotoxemic shock. Thus, the purpose of the present study was to
      assess the effect of the intravenous (i.v.) and intracereboventricular (i.c.v.)
      administration of aminoguanidine, an iNOS blocker, on plasma ANP levels and MAP
      during experimental endotoxemic shock. Experiments were performed on adult male
      Wistar rats weighing 180-240 g. Rats were injected i.v. by bolus injection with
      1.5 mg/kg of Lipopolysaccharide (LPS) or saline (0.5 mL) and were decapitated 2,
      4 and 6 h after LPS injection for ANP determination by radioimmunoassay. In a
      separate set of experiments, rats received intravenous (i.v.) (100 mg/kg) or
      intracerebroventricular (i.c.v.) (250 microg in a final volume of 2 microL)
      injection of aminoguanidine (AG). Thirty minutes after the i.c.v. or i.v.
      injections, animals received LPS and were decapitated 2, 4 and 6 h later to
      determine plasma ANP concentration. In the two set of experiments MAP and heart
      rate (HR) were measured each 15 min for a period of 6 h using a polygraph. When
      animals were injected with LPS, a reduction (p<0.01) in MPA and an increase in HR
      occurred. A significant increase in plasma ANP concentration occurred, coinciding
      with the period of drop in blood pressure. We found a significant increase in
      plasma ANP concentration after AG plus LPS injection, when compared to the rats
      treated with LPS plus saline. Further, the administration of AG plus LPS
      attenuated the decrease in the MAP after LPS and attenuated the increase in the
      HR when compared to the rats treated with LPS plus saline. Our study suggests
      that inducible NOS pathway may activate an inhibitory control mechanism that
      attenuates ANP secretion, which is not regulated by the changes in blood
      pressure.

PMID- 17223209
TI  - Utility of plasma apelin and other indices of cardiac dysfunction in the clinical
      assessment of patients with dilated cardiomyopathy.
AB  - Apelin is a recently discovered peptide ligand reported to be involved in the
      regulation of cardiovascular homeostasis. The exact role of apelin in the
      pathophysiology of congestive heart failure has remained obscure, and the
      reported circulating levels of apelin in patients with heart failure have been
      contradictory. To establish the role of apelin in the assessment of cardiac
      dysfunction we measured plasma apelin levels in 65 patients with congestive heart
      failure caused by idiopathic dilated cardiomyopathy (IDC) and 14 healthy
      volunteers by specific radioimmunoassay. IDC patients were carefully examined
      including echocardiography, both-sided cardiac catheterization and
      cardiopulmonary exercise test. In addition, plasma levels of N-terminal pro-brain
      natriuretic peptide (NT-proBNP), N-terminal pro-atrial natriuretic peptide (NT
      proANP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-alpha), epinephrine
      and norepinephrine were determined. Plasma apelin levels were similar in IDC
      patients (median 26.5 pg/ml, range<3.40-97.6 pg/ml) and in control subjects
      (median 24.1 pg/ml, range 19.0-28.7 pg/ml; p=NS). Unlike the levels of NT-proBNP,
      IL-6, TNF-alpha, and norepinephrine, plasma apelin levels did not reflect the
      severity of heart failure. Our study demonstrates that although disturbed apelin
      APJ signalling in heart may play a role in the pathophysiology of heart failure,
      circulating apelin levels cannot be applied in the clinical assessment of
      patients with chronic left ventricular dysfunction.

PMID- 17223207
TI  - Injections of the selective adenosine A2A antagonist MSX-3 into the nucleus
      accumbens core attenuate the locomotor suppression induced by haloperidol in
      rats.
AB  - There is considerable evidence of interactions between adenosine A2A receptors
      and dopamine D2 receptors in striatal areas, and antagonists of the A2A receptor
      have been shown to reverse the motor effects of DA antagonists in animal models.
      The D2 antagonist haloperidol produces parkinsonism in humans, and also induces
      motor effects in rats, such as suppression of locomotion. The present experiments
      were conducted to study the ability of the adenosine A2A antagonist MSX-3 to
      reverse the locomotor effects of acute or subchronic administration of
      haloperidol in rats. Systemic (i.p.) injections of MSX-3 (2.5-10.0 mg/kg) were
      capable of attenuating the suppression of locomotion induced by either acute or
      repeated (i.e., 14 day) administration of 0.5 mg/kg haloperidol. Bilateral
      infusions of MSX-3 directly into the nucleus accumbens core (2.5 microg or 5.0
      microg in 0.5 microl per side) produced a dose-related increase in locomotor
      activity in rats treated with 0.5 mg/kg haloperidol either acutely or repeatedly.
      There were no overall significant effects of MSX-3 infused directly into the
      dorsomedial nucleus accumbens shell or the ventrolateral neostriatum. These
      results indicate that antagonism of adenosine A2A receptors can attenuate the
      locomotor suppression produced by DA antagonism, and that this effect may be at
      least partially mediated by A2A receptors in the nucleus accumbens core. These
      studies suggest that adenosine and dopamine systems interact to modulate the
      locomotor and behavioral activation functions of nucleus accumbens core.

PMID- 17223210
TI  - Role of pre-infarction angina and inflammatory status in the extent of
      microvascular obstruction detected by MRI in myocardial infarction patients
      treated by PCI.
AB  - BACKGROUND/OBJECTIVES: The extent of microvascular obstruction (MVO) during
      myocardial infarction referred to as the "no-reflow phenomenon", may determine
      myocardial damage. Our study aimed to investigate the incidence and the
      influencing factors of MVO in patients with ST-elevation myocardial infarction
      (STEMI) treated by primary percutaneous intervention (PCI). PATIENTS, METHODS:
      Using contrast-enhanced MRI, microvascular obstruction was defined as early
      hypoenhancement. Contrast defects were scored from 0 (no hypoenhancement) to 3
      (strong hypoenhancement). 50 patients (56+/-11 years) with STEMI underwent PCI.
      Contrast-enhanced MRI (6+/-2 days after STEMI) and biochemical parameters were
      evaluated. RESULTS: Microvascular obstruction (score 1 to 3) was observed in 90%
      of the patients and major microvascular obstruction (score 2-3) in 54%. In
      univariate analysis, leukocytes and CRP levels were associated with MVO, whereas
      pre-infarction angina and prior medication by aspirin or calcium channel
      antagonist appeared protective. Microvascular obstruction intensity positively
      correlated with baseline inflammation status assessed by C-reactive protein and
      leukocytes (rho=0.43 and rho=0.44; p=0.003), the peak of CK (rho=0.56; p=0.01) or
      Troponin I (rho=0.59; p=0.01) and negatively correlated with LVEF (rho=-0.44;
      p=0.002). Multivariate analysis identified the absence of pre-infarction angina
      as the only independent predictor for microvascular obstruction (odds ratio,
      8.35, 95% confidence interval 1.27-54.71; p=0.027). CONCLUSION: MRI-detected
      microvascular obstruction has a high incidence in patients with STEMI treated by
      primary PCI and determines post-MI LVEF even in patients with post PCI TIMI 3
      flow score. Pre-infarction angina appears to be an independent determinant of the
      extent of MVO detected by MRI.

PMID- 17223211
TI  - Endothelial nitric oxide synthase polymorphisms and hypertension: improved
      clinical evidence derived from haplotype analysis.

PMID- 17223212
TI  - One year outcomes after glucose-insulin-potassium in ST elevation myocardial
      infarction. The Glucose-insulin-potassium study II.
AB  - BACKGROUND: There are conflicting data concerning the effect of treatment with
      glucose-insulin-potassium (GIK) in ST segment elevation myocardial infarction
      (STEMI). Early studies showed beneficial effects of GIK, however, recent large
      sample size trials did not confirm this, or suggested only benefits in patients
      without heart failure. We aimed to evaluate long-term effects of GIK in patients
      with STEMI without signs of heart failure, all treated with reperfusion therapy.
      METHODS: From August 2003 to December 2004, 889 STEMI patients without signs of
      heart failure were randomized to standard care (N=445) or additional GIK infusion
      (N=444). Glucose-potassium (20% glucose with 80 mmol potassium/l) was infused at
      2 ml/kg body weight per hour for 12 h through a peripheral line. Short-acting
      insulin was started according to admission glucose and adjusted based on hourly
      measured glucose. Clinical end points were of number of death, reinfarction and
      revascularization at 1 year. RESULTS: One year follow-up was available in 864
      patients (97.2%), 432 in the GIK group and 432 in the control group. Mortality
      rate was 5.3% in GIK and 3.9% in control patients, p=0.33. Rates of reinfarction
      and revascularization 4.6% vs. 4.6% and 15.5% and 15.0%, in GIK vs. control
      patients. CONCLUSION: In patients with STEMI without signs of heart failure
      treated with reperfusion therapy, GIK therapy offers no clinical benefit at 1
      year.

PMID- 17223213
TI  - Serologic surveillance of swine H1 and H3 and avian H5 and H9 influenza A virus
      infections in swine population in Korea.
AB  - Influenza A is a respiratory disease common in the swine industry. Three
      subtypes, H1N1, H1N2 and H3N2 influenza A viruses, are currently co-circulating
      in swine populations in Korea. An outbreak of the highly pathogenic avian
      influenza H5N1 virus occurred in domestic bird farms in Korea during the winter
      season of 2003. Pigs can serve as hosts for avian influenza viruses, enabling
      passage of the virus to other mammals and recombination of mammalian and avian
      influenza viruses, which are more readily transmissible to humans. This study
      reports the current seroprevalence of swine H1 and H3 influenza in swine
      populations in Korea by hemagglutination inhibition (HI) assay. We also
      investigated whether avian H5 and H9 influenza transmission occurred in pigs from
      Korea using both the HI and neutralization (NT) tests. 51.2% (380/742) of serum
      samples tested were positive against the swine H1 virus and 43.7% (324/742) were
      positive against the swine H3 virus by HI assay. The incidence of seropositivity
      against both the swine H1 virus and the swine H3 virus was 25.3% (188/742). On
      the other hand, none of the samples tested showed seropositivity against either
      the avian H5 virus or the avian H9 virus by the HI and NT tests. Therefore, we
      report the high current seroprevalence and co-infectivity of swine H1 and H3
      influenza viruses in swine populations and the lack of seroepidemiological
      evidence of avian H5 and H9 influenza transmission to Korean pigs.

PMID- 17223214
TI  - Molecular and functional characterization of Lactobacillus sanfranciscensis
      strains isolated from sourdoughs.
AB  - Fifty isolates of Lactobacillus sanfranciscensis from Italian sourdoughs were
      identified and typed by a polyphasic approach which included genotypic and
      phenotypic criteria. Genotypic diversity was characterized by Ribosomal
      Intergenic Spacer Analysis (RISA) of PCR amplified 16S-23S rDNA spacer region,
      denaturing gradient gel electrophoresis (DGGE) of PCR amplified rpoB (beta
      subunit of RNA polymerase) gene, and rep-PCR (PCR amplification of repetitive
      bacterial DNA elements) analyses. The RISA analysis produced a unique
      electrophoretical profile of four bands (ranging from 300 to 600 bp) for all L.
      sanfranciscensis isolates. The DGGE analysis of rpoB gene allowed the subdivision
      of isolates in four clusters. The resolution found by using rep-PCR with primers
      BOXA1R and REP1R-I/REP2-I allowed the widening of the level of isolates
      heterogeneity. Phenotypic diversity was evaluated by Biolog System and
      characterization of several technological traits (e.g., acidification kinetics,
      proteinase and peptidase activities). L. sanfranciscensis isolates used a large
      varieties of carbon sources such as dextrin, D-fructose, L-fucose, alpha-D
      glucose, maltose, palatinose, L-rhanmose, L- and D,L-lactic acids and L
      methionine. The acidification activity and related quotient of fermentation, and
      the peptidase (PepN, PepV, PepT, PepI, PepX, PepQ and PepR) activities markedly
      varied among strains. The same was found concerning the capacity to liberate
      amino acids during sourdough fermentation. This study could be considered as an
      example of a computerized analysis of the genotypic and phenotypic traits to
      reliably and rapidly differentiate sourdough isolates. Although some L.
      sanfranciscensis isolates combined several technological traits, the association
      of more selected strains seemed to be a requisite to get optimal sourdough
      characteristics.

PMID- 17223215
TI  - A simple enzymatic synthesis of 4-nitrophenyl beta-1,4-D-xylobioside, a
      chromogenic substrate for assay and differentiation of endoxylanases.
AB  - A simple procedure has been elaborated for preparation of 4-nitrophenyl beta-d
      xylopyranosyl-1,4-beta-d-xylopyranoside (NPX(2)), a chromogenic substrate of some
      endo-beta-1,4-xylanases. The procedure is based on a self-transfer reaction from
      4-nitrophenyl beta-d-xylopyranoside catalyzed by an Aureobasidium pullulans and
      Aspergillus niger beta-xylosidases. Both enzymes catalyzed only the formation of
      4-nitrophenyl glycosides of beta-1,4-xylobiose with a small admixture of 4
      nitrophenyl glycoside of beta-1,3-xylobiose. The highest yields of the NPX(2)
      (19.4%) was obtained at pH 5.5. The removal of the beta-1,3-isomer from NPX(2) is
      not necessary for quantification of endo-beta-1,4-xylanase activity since it is
      not attacked by endo-beta-1,4-xylanases. In contrast to GH family 5 xylanase from
      Erwinia chrysanthemi, which did not attack NPX(2), all family 10 and 11 xylanases
      cleaved the chromogenic substrate exclusively between xylobiose and the aromatic
      aglycone. Significant differences in the K(m) values of GH10 and GH11 xylanases
      suggested that activities of these enzymes could be selectively quantified in the
      mixtures using various concentrations of NPX(2). Moreover, NPX(2) could serve as
      an ideal substrate to follow the interaction of endo-beta-1,4-xylanases with
      various xylanase inhibitors.

PMID- 17223216
TI  - Surface hydrolysis of polyacrylonitrile with nitrile hydrolysing enzymes from
      Micrococcus luteus BST20.
AB  - A new Micrococcus luteus strain BST20 was isolated with ability to metabolize PAN
      polymers as sole carbon source. Out of seven synthetized PAN copolymers
      containing different moieties of acrylic acid and/or vinyl acetate the polymer
      with lowest crystallinity (PAN with 5% vinyl acetate) was most easily
      metabolized. (13)C labelled PAN was completely converted to the acrylic acid by
      this strain. M. luteus BST20 produced membrane-bound nitrile hydrolysing enzymes
      able to convert nitrile groups on PAN powder surface to the corresponding acids.
      Similarly, nitrile groups on PAN fabrics were transformed to the corresponding
      acid as indicated by an K/S increased after dying with Methylene blue and the
      released ammonia. On small soluble substrates the enzyme system showed a
      preference for aliphatic and aromatic substituted aliphatic nitriles.

PMID- 17223217
TI  - Efficacy and tolerability of vildagliptin monotherapy in drug-naive patients with
      type 2 diabetes.
AB  - This 24-week, double-blind, randomized, multicenter, placebo-controlled, parallel
      group study performed in 354 drug-naive patients with type 2 diabetes (T2DM)
      assessed efficacy and tolerability of vildagliptin (50mg qd, 50mg bid, or 100mg
      qd). The primary assessment was change from baseline to endpoint in hemoglobin
      A1c (A1C), comparing vildagliptin to placebo by ANCOVA. Baseline A1C averaged
      8.4% and the between-treatment difference (vildagliptin-placebo) in adjusted mean
      change (AMDelta) in A1C was -0.5+/-0.2% (P=0.011), -0.7+/-0.2% (P<0.001), and 
      0.9+/-0.2% (P<0.001) in patients receiving vildagliptin 50 mg qd, 50 mg bid, or
      100 mg qd, respectively. Baseline FPG averaged 10.5 mmol/L; the between-treatment
      difference in AMDelta FPG was -0.6+/-0.4 mmol/L in patients receiving
      vildagliptin 50mg qd and -1.3+/-0.4 mmol/L (P=0.001) in both groups receiving
      100mg daily. Relative to baseline, body weight did not change significantly in
      any of the three vildagliptin groups and decreased by 1.4+/-0.4 kg in the placebo
      group. Adverse events (AEs) occurred with similar frequency in each group: 55.8%,
      59.3%, 59.3%, and 57.6% of patients receiving vildagliptin 50 mg qd, 50 mg bid,
      100 mg qd, or placebo, respectively, experienced an AE. No confirmed hypoglycemia
      was reported. CONCLUSION: Vildagliptin is effective and well-tolerated in drug
      naive patients with T2DM and 100 mg vildagliptin provides similar clinical
      benefit whether given as single or in divided doses.

PMID- 17223218
TI  - In vitro veritas? The challenges of studying hepatitis C virus infectivity in a
      test tube.

PMID- 17223219
TI  - New perspectives for the treatment of cholestasis: lessons from basic science
      applied clinically.

PMID- 17223220
TI  - Antiviral therapy in liver transplant recipients: is SVR the only endpoint that
      matters?

PMID- 17223221
TI  - In situ localization of gene transcriptions for monoterpene synthesis in
      irregular parenchymic cells surrounding the secretory cavities in rough lemon
      (Citrus jambhiri).
AB  - A cDNA (RlemispF) encoding 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase,
      an enzyme of the methyl erythritol phosphate (MEP) pathway, and two homologs
      (RlemTPS1 and RlemTPS2) of citrus monoterpene synthase cDNA were isolated from
      the rough lemon (Citrus jambhiri). Transient localization of all or a part of
      RlemispF fused to a green fluorescence protein using particle gun-mediated DNA
      delivery localized RlemispF in the chloroplast. Transcripts of RlemispF and other
      monoterpene synthase genes are constitutively expressed in leaves of rough lemon.
      Transcript accumulations of RlemispF and RlemTPS1 were not induced by microbe
      attacks, but microbe attack weakly induced RlemTPS2 expression. Wounding
      decreased RlemispF expression. RlemispF and two different monoterpene synthase
      genes were specifically expressed in the epithelial tissue cells with dense
      cytoplasm that surround secretory cavities, which form a broadly round package
      containing a large volume of essential oils composed of monoterpenes.
      Interestingly, although expressions of RlemTPS1 and RlemTPS2 were detected at
      both mature and developing secretory cavities, the RlemispF-expressing cells were
      found more at around developing secretory cavities.

PMID- 17223222
TI  - NADPH oxidase-dependent hydrogen peroxide production, induced by salinity stress,
      may be involved in the regulation of total calcium in roots of wheat.
AB  - Hydrogen peroxide (H(2)O(2)) is often generated by cells and tissues under
      environmental stress. In this work, we provide evidence that plasma membrane (PM)
      NADPH oxidase-dependent H(2)O(2) production might act as an intermediate step in
      the NaCl-induced elevation of calcium (Ca) in roots of wheat. Remarkable
      increases in the content of total Ca were observed not only in roots exposed to
      NaCl but also in roots of seedlings exposed to exogenous H(2)O(2). In roots,
      H(2)O(2) production increased upon exposure to salt stress. PM vesicles were
      isolated from roots, and NADPH oxidase activity was determined by measuring
      superoxide anion (O(2)(-)) production. NADPH oxidase-dependent O(2)(-) production
      was 11.6nmolmg(-1)proteinmin(-1) in control vesicles, but 19.6nmol after NaCl
      treatment (24h), indicating that salt stress resulted in the activation of the PM
      NADPH oxidase. Furthermore, the NaCl-induced increase in total Ca was partially
      abolished by the addition of 150U/mL catalase (CAT), a H(2)O(2) scavenger, and
      also by 10microM diphenylane iodonium (DPI), a NADPH oxidase inhibitor. This data
      suggest that NADPH oxidase-dependent H(2)O(2) production might be involved in the
      modulation of the Ca content in wheat roots. In conclusion, our results show that
      salinity stress increases the total Ca content of wheat roots, which is partly
      due to PM NADPH oxidase-dependent H(2)O(2) generation.

PMID- 17223223
TI  - Overexpression of citrus polygalacturonase-inhibiting protein in citrus black rot
      pathogen Alternaria citri.
AB  - The rough lemon (Citrus jambhiri) gene encoding polygalacturonase-inhibiting
      protein (RlemPGIPA) was overexpressed in the pathogenic fungus Alternaria citri.
      The overexpression mutant AcOPI6 retained the ability to utilize pectin as a sole
      carbon source, and the overexpression of polygalacturonase-inhibiting protein did
      not have any effect on the growth of AcOPI6 in potato dextrose and pectin medium.
      The pathogenicity of AcOPI6 to cause a black rot symptom in citrus fruits was
      also unchanged. Polygalacturonase-inhibiting protein was secreted together with
      endopolygalacturonase into culture filtrates of AcOPI6, and oligogalacturonides
      were digested from polygalacturonic acid by both proteins in the culture
      filtrates. The reaction mixture containing oligogalacturonides possessed activity
      for induction of defense-related gene, RlemLOX, in rough lemon leaves.

PMID- 17223224
TI  - Dinitro-o-cresol induces apoptosis-like cell death but not alternative oxidase
      expression in soybean cells.
AB  - In plants, programmed cell death is thought to be activated during
      differentiation and in response to biotic and abiotic stresses. Although its
      mechanisms are far less clear, several morphological and biochemical features
      have been described in different experimental systems, including DNA laddering
      and cytosolic protease activation. Moreover, plant mitochondria have an
      alternative terminal oxidase (AOX), which is thought to be involved in protection
      against increased reactive oxygen species production, perhaps representing a
      mechanism to prevent programmed cell death. In this study, we analysed cell death
      induced by the herbicide dinitro-o-cresol (DNOC) in soybean (Glycine max)
      suspension cell cultures and evaluated biochemical and molecular events
      associated with programmed cell death. AOX capacity and expression were also
      determined. DNOC-treated cells showed fragmented nuclear DNA as assessed by an in
      situ assay that detects 3'-OH ends. In addition, specific colorimetric assays and
      immunoblot analysis revealed activation of caspase-3-like proteins and release of
      cytochrome c from mitochondria, respectively, confirming the apoptotic-like
      phenotype. Surprisingly, AOX capacity and protein levels decreased in DNOC
      treated cells, suggesting no association between cell death and AOX under these
      experimental conditions. In conclusion, the results show that DNOC induces
      programmed cell death in soybean cells, suggesting that plants and animals might
      share similar pathways. Further, the role of AOX in cell death has not been
      confirmed, and may depend on the nature and intensity of stress conditions.

PMID- 17223225
TI  - Exogenous proline and glycinebetaine increase NaCl-induced ascorbate-glutathione
      cycle enzyme activities, and proline improves salt tolerance more than
      glycinebetaine in tobacco Bright Yellow-2 suspension-cultured cells.
AB  - Up-regulation of the antioxidant system provides protection against NaCl-induced
      oxidative damage in plants. Antioxidants and activity of enzymes involved in the
      ascorbate-glutathione (ASC-GSH) cycle in tobacco Bright Yellow-2 (BY-2) were
      investigated to assess the antioxidant protection offered by exogenous proline
      and glycinebetaine (betaine from now on) against salt stress using cells grown in
      suspension culture. Reduced ascorbate (ASC) was detected in BY-2 cells but
      dehydroascorbate (DHA) was not. Large quantities of a reduced form of glutathione
      (GSH) and smaller quantities of an oxidized form of glutathione (GSSG) were
      detected in BY-2 cells. Salt stress significantly reduced the contents of ASC and
      GSH as well as activities of ASC-GSH cycle enzymes such as ascorbate peroxidase
      (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR),
      and glutathione reductase (GR). Exogenous proline or betaine increased the
      activities of all enzymes except MDHAR involved in NaCl-induced ASC-GSH cycle.
      Levels of ASC and GSH in BY-2 cells under salt stress were lower in the presence
      of proline or betaine than in the absence of proline or betaine whereas there was
      no difference in redox status. Proline proved more effective than betaine in
      maintaining the activity of enzymes involved in NaCl-induced ASC-GSH cycle.
      Neither proline nor betaine had any direct protective effect on NaCl-induced
      enzyme activity involved in the antioxidant system; however, both improved salt
      tolerance by increasing enzyme activity. The present study, together with our
      earlier findings [Hoque MA, Okuma E, Banu MNA, Nakamura Y, Shimoishi Y, Murata Y.
      Exogenous proline mitigates the detrimental effects of salt stress more than
      exogenous betaine by increasing antioxidant enzyme activities. J Plant Physiol
      2006;164:553-61.], suggests that proline offered greater protection against salt
      stress than betaine did because proline was more effective in increasing the
      activity of enzymes involved in the antioxidant system.

PMID- 17223226
TI  - Specificity of expression of the GUS reporter gene (uidA) driven by the tobacco
      ASA2 promoter in soybean plants and tissue cultures.
AB  - Twelve independent lines were transformed by particle bombardment of soybean
      embryogenic suspension cultures with the tobacco anthranilate synthase (ASA2)
      promoter driving the uidA (beta-glucuronidase, GUS) reporter gene. ASA2 appears
      to be expressed in a tissue culture specific manner in tobacco (Song H-S,
      Brotherton JE, Gonzales RA, Widholm JM. Tissue culture specific expression of a
      naturally occurring tobacco feedback-insensitive anthranilate synthase. Plant
      Physiol 1998;117:533-43). The transgenic lines also contained the hygromycin
      phosphotransferase (hpt) gene and were selected using hygromycin. All the
      selected cultures or the embryos that were induced from these cultures expressed
      GUS measured histochemically. However, no histochemical GUS expression could be
      found in leaves, stems, roots, pods and root nodules of the plants formed from
      the embryos and their progeny. Pollen from some of the plants and immature and
      mature seeds and embryogenic cultures initiated from immature cotyledons did show
      GUS activity. Quantitative 4-methylumbelliferyl-glucuronide (MUG) assays of the
      GUS activity in various tissues showed that all with observable histochemical GUS
      activity contained easily measurable activities and leaves and stems that showed
      no observable histochemical GUS staining did contain very low but measurable MUG
      activity above that of the untransformed control but orders of magnitude lower
      than the constitutive 35S-uidA controls used. Low but clearly above background
      levels of boiling sensitive GUS activity could be observed in the untransformed
      control immature seeds and embryogenic cultures using the MUG assay. Thus in
      soybean the ASA2 promoter drives readily observable GUS expression in tissue
      cultures, pollen and seeds, with only extremely low levels seen in vegetative
      tissues of the plants. The ASA2 driven expression seen in mature seed was,
      however, much lower than that seen with the constitutive 35S promoter; less than
      2% in seed coats and less than 0.13% in cotyledons and embryo axes. The
      predominate tissue culture specific expression pattern of the ASA2 promoter may
      be useful for genetic transformation of crops.

PMID- 17223227
TI  - Cytochemical immuno-localization of allene oxide cyclase, a jasmonic acid
      biosynthetic enzyme, in developing potato stolons.
AB  - The involvement of jasmonates in the tuber development has been proved by the
      presence of many of these compounds in potato stolons, modification of their
      levels during the transition of the stolon into tuber, and induction of cell
      expansion upon exogenous jasmonates treatment. However, to date there is only
      little evidence of the presence of the jasmonic acid-biosynthetic enzymes in
      stolons or young tubers. As allene oxide cyclase represents the major control
      point for jasmonic acid biosynthesis, we studied the occurrence of allene oxide
      cyclase by immunological approaches in the early stages of tuber formation. In
      developing stolons, allene oxide cyclase as well as lipoxygenase were clearly
      detectable, but their levels did not change during development. Jasmonic acid
      treatment for 24h, however, increased lipoxygenase and allene oxide cyclase
      protein levels in both developmental stages analyzed. In longitudinal sections of
      stolons of stages 1 and 2, allene oxide cyclase and lipoxygenase occurred in the
      apex and along the stolon axis. Allene oxide cyclase was clearly detectable in
      epidermal, cortical and pith parenchymatic cells, showing the highest levels in
      vascular tissues surrounding cells. Lipoxygenase was mainly located in the
      parenchymatic cortex cells. The occurrence of allene oxide cyclase in stolons
      together with the previous identification of jasmonates from developing stolons
      reveals that these organs are capable to synthesize and metabolize jasmonates.

PMID- 17223228
TI  - NPY receptors in human cancer: a review of current knowledge.
AB  - Many peptide hormone receptors are over-expressed in human cancer, permitting an
      in vivo targeting of tumors for diagnostic and therapeutic purposes. NPY
      receptors are novel and promising candidates in this field. Using in vitro
      receptor autoradiography, Y1 and Y2 receptors have been found to be expressed in
      breast carcinomas, adrenal gland and related tumors, renal cell carcinomas, and
      ovarian cancers in both tumor cells and tumor-associated blood vessels.
      Pathophysiologically, tumoral NPY receptors may be activated by endogenous NPY
      released from intratumoral nerve fibers or tumor cells themselves, and mediate
      NPY effects on tumor cell proliferation and tumoral blood supply. Clinically,
      tumoral NPY receptors may be targeted with NPY analogs coupled with adequate
      radionuclides or cytotoxic agents for a scintigraphic tumor imaging and/or tumor
      therapy.

PMID- 17223229
TI  - Neuropeptide Y (NPY) cleaving enzymes: structural and functional homologues of
      dipeptidyl peptidase 4.
AB  - N-terminal truncation of NPY has important physiological consequences, because
      the truncated peptides lose their capability to activate the Y1-receptor. The
      sources of N-terminally truncated NPY and related peptides are unknown and
      several proline specific peptidases may be involved. First, we therefore provide
      an overview on the peptidases, belonging to structural and functional homologues
      of dipeptidyl peptidase 4 (DP4) as well as aminopeptidase P (APP) and thus,
      represent potential candidates of NPY cleavage in vivo. Second, applying
      selective inhibitors against DP4, DP8/9 and DP2, respectively, the enzymatic
      distribution was analyzed in brain extracts from wild type and DP4 deficient F344
      rat substrains and human plasma samples in activity studies as well as by matrix
      assisted laser desorption/ionisation-time of flight (MALDI-TOF)-mass
      spectrometry. Third, co-transfection of Cos-1 cells with Dpp4 and Npy followed by
      confocal lasermicroscopy illustrated that hNPY-dsRed1-N1 was transported in large
      dense core vesicles towards the membrane while rDP4-GFP-C1 was transported
      primarily in different vesicles thereby providing no clear evidence for co
      localization of NPY and DP4. Nevertheless, the review and experimental results of
      activity and mass spectrometry studies support the notion that at least five
      peptidases (DP4, DP8, DP9, XPNPEP1, XPNPEP2) are potentially involved in NPY
      cleavage while the serine protease DP4 (CD26) could be the principal peptidase
      involved in the N-terminal truncation of NPY. However, DP8 and DP9 are also
      capable of cleaving NPY, whereas no cleavage could be demonstrated for DP2.

PMID- 17223230
TI  - Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral
      activity against HIV-1 wild-type and mutant strains.
AB  - Novel diarylpyrimidines (DAPY), which represent next generation of non-nucleoside
      reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities
      against human immunodeficiency virus type I (HIV-1) assessed. Modulations at
      positions 2 and 6 of the left phenyl ring generated interesting derivatives of
      TMC278 displaying high potency against wild-type and mutant viruses compared to
      nevirapine and efavirenz. The pharmacokinetic profile of the best newly
      synthesized DAPY was evaluated and compared with TMC278 now in phase II clinical
      trials.

PMID- 17223231
TI  - Guidelines for the replacement of temporomandibular joints in the United Kingdom.
AB  - BAOMS has requested that guidelines be formulated for the replacement of the
      temporomandibular joint (TMJ). This is an expensive and technique sensitive
      method of TMJ reconstruction and in the current climate warrants an agreed
      approach. The following document states the indications and contraindications for
      this technique as discussed and agreed amongst surgeons currently carrying out
      this procedure in the UK.

PMID- 17223232
TI  - A pilot study of eye movement desensitisation and reprocessing treatment (EMDR)
      for post-traumatic stress after childbirth.
AB  - OBJECTIVE: to explore the possibility of using eye movement desensitisation and
      reprocessing (EMDR) to treat women who have experienced post-traumatic stress
      after childbirth. DESIGN: the pilot study consisted of a 'before and after'
      treatment design combined with follow-up measurements 1-3 years after EMDR
      treatment. Quantitative data from questionnaires (Traumatic Event Scale [TES])
      were collected. In addition, qualitative data from individual interviews with the
      participants were collected as well as data from the psychotherapist's treatment
      notes of the EMDR treatment sessions. SETTING: the north of Sweden. PARTICIPANTS:
      four women with post-traumatic stress disorder (PTSD) after childbirth (one
      pregnant and three non-pregnant). FINDINGS: all participants reported reduction
      of post-traumatic stress after treatment. After 1-3 years, the beneficial effects
      of EMDR treatment remained for three of the four women. Symptoms of intrusive
      thoughts and avoidance seemed most sensitive for treatment. IMPLICATIONS FOR
      PRACTICE: EMDR might be a useful tool in the treatment of non-pregnant women
      severely traumatised by childbirth; however, further research is required.

PMID- 17223233
TI  - Irreducible Galeazzi fracture-dislocation due to intra-articular fracture of the
      distal ulna.
AB  - Irreducible Galeazzi fracture-dislocation is a rare injury. Structures that
      mechanically block the reduction are usually soft tissues. We present an
      irreducible case due to distal ulnar intra-articular fracture.

PMID- 17223234
TI  - The SF-6D health utility index in carpal tunnel syndrome.
AB  - Cost effectiveness is an important factor to consider when choosing between
      various hand surgical interventions. Health utility measures can be used to
      determine cost effectiveness. The SF-6D is a health utility index derived from 11
      items of the SF-36 quality of life questionnaire; values range from 0.296 to 1.0
      ("perfect" health). We evaluated the validity of the SF-6D in patients with
      carpal tunnel syndrome (CTS) who completed the SF-36 and the CTS symptom severity
      and functional status questionnaire before and 3 months after carpal tunnel
      release. Complete responses to the SF-6D items were available for 100 patients at
      baseline and 95 patients at baseline and follow-up. The mean SF-6D health utility
      index was 0.69 (SD 0.13) before surgery and 0.77 (SD 0.13) after surgery
      (moderate effect size). The SF-6D could discriminate between patient groups
      differing in self-rated global health and in whether, or not, they had a minimal
      clinically important improvement in CTS symptom severity after surgery. The SF-6D
      appears to be a valid measure of health utilities in patients with CTS and can be
      used in cost effectiveness studies.

PMID- 17223235
TI  - Effects of Phos-Chek G75-F and Silv-Ex on red-winged blackbird (Agelaius
      phoeniceus) embryos.
AB  - Effects of field application levels of wildfire control chemicals, Phos-Chek G75
      F (PC) and Silv-Ex (SE), were examined on red-winged blackbird (Agelaius
      phoeniceus) embryos. Embryos were more sensitive to PC and SE when eggs were
      immersed for 10s at an early developmental stage (days 3-5 of incubation) than at
      a later stage (days 6-9 of incubation). The LC(50) (concentration causing 50%
      mortality) for early stage embryos exposed to PC was 213.3g/L (slope=1.6; 95%
      confidence interval [CI]=129.1-326.1). The no observed effect concentration
      (NOEC) was below 135g PC/L, which caused a significant increase in embryonic
      mortality and represents the lowest field coverage level of 1gal/100feet(2). The
      LC(50) for early stage embryos exposed to SE was 19.8g/L (slope=1.5; 95% CI=11.7
      52.2). Significant mortality was observed at 10g SE/L and marginal at 7.5g SE/L
      with an apparent NOEC around 5g SE/L. Neither chemical resulted in apparent
      developmental malformations.

PMID- 17223236
TI  - Cadmium concentrations in tissues of willow ptarmigan (Lagopus lagopus) and rock
      ptarmigan (Lagopus muta) in Nunavik, Northern Quebec.
AB  - Willow and rock ptarmigan were obtained from Northern Quebec. Willow ptarmigan
      were found to have mean cadmium concentrations of 179.7 microg/g (dw) in the
      kidneys and 25.8 microg/g (dw) in the liver; these levels were three times higher
      than those found in the rock ptarmigan. The cadmium levels in the ptarmigan were
      below the threshold above which adverse effects can be observed in birds. The
      difference between the two ptarmigan species in cadmium content is explained by
      the diet. A comparison of their diet showed that willow, which stores cadmium, is
      an important food resource for willow ptarmigan but not for rock ptarmigan.
      Because there is limited information available on the consumption of ptarmigan
      kidneys and liver by the Inuit, and the fact that this is a traditional way of
      life and provides nutritional benefits to the Inuit population, no consumption
      guidelines are proposed.

PMID- 17223237
TI  - Estimates of ambient background concentrations of trace metals in soils for risk
      assessment.
AB  - Site-specific or soil type-specific ambient background concentrations (ABCs) of
      trace metals in soils are needed for risk assessment. We investigated three
      different methods for estimating ABCs in soils using a dataset of 5691 soil
      samples from England and Wales. The concentrations of Co, Cr and Ni were strongly
      associated with Al and Fe, and multiple regressions explained 62-85% of their
      variation, and Al and Fe can therefore be used to predict ABCs for these metals.
      Soil texture had a major influence on the concentrations of Cd, Co, Cr, Cu, Ni
      and Zn, and the medians were 3-5 fold higher in clayey than in sandy soils. This
      was used to predict texture-specific ABCs. Lead concentration was higher in
      acidic peaty soils than in other soils. A probability graph method was used to
      estimate ABC for Pb in a population of relatively uncontaminated soils. Potential
      applications of ABCs are discussed.

PMID- 17223238
TI  - Coping with hallucinated voices in schizophrenia: a review of self-initiated
      strategies and therapeutic interventions.
AB  - This article reviews the state of knowledge about strategies used by people with
      a diagnosis of schizophrenia to cope with hallucinated voices, and considers the
      role of coping in psychological treatments for persisting symptoms. The use of
      self-initiated ('natural') coping strategies appears almost universal amongst
      voice-hearers. These strategies are similar across cultures, and include diverse
      behaviours, only a minority of which is specific to hallucinations. Most
      strategies are reported by at least some users to be effective, but more
      sophisticated outcome studies are lacking. Some evidence for the efficacy of
      certain behavioural techniques of coping, for the manipulation of auditory input,
      and for strategies involving subvocalisation, is available from experimental
      studies. Therapeutic enhancement of natural coping strategies for persisting
      symptoms has demonstrated some efficacy, but its benefit for voices is unknown.
      Despite this, it has become an established part of some CBT interventions for
      psychosis. Further advances in knowledge and practice may come from utilisation
      of coping models in research, longitudinal and ideographic methods of study and a
      movement away from descriptive coping lists to investigations of coping styles,
      mechanisms of action, and the process of coping.

PMID- 17223239
TI  - Examining attribution model of self-stigma on social support and psychological
      well-being among people with HIV+/AIDS.
AB  - Among various infectious diseases, HIV/AIDS is considered to be one of the most
      stigmatizing conditions. Using a prospective design, the present study attempted
      to test the attributional pathway from perceived control to responsibility to
      self-blame and finally to self-stigmatization, and to examine the social and
      psychological sequelae of stigma among a sample of 119 people with HIV/AIDS
      (PWHA) in Hong Kong. Structural equation modeling findings showed that the model
      had good fit to the data. Although the linkage between the attributions of
      control, responsibility, and blame was confirmed, the relationship of blame to
      self-stigma was not significant. Self-stigma was found to dampen social support
      and lead to psychological distress half a year later. The present study
      challenged the adequacy of attributional factors in understanding self
      stigmatization and demonstrated the impact of stigma on psychological adjustment
      among PWHA.

PMID- 17223240
TI  - An ERP study on self-relevant object recognition.
AB  - We performed an event-related potential study to investigate the self-relevance
      effect in object recognition. Three stimulus categories were prepared: SELF
      (participant's own objects), FAMILIAR (disposable and public objects, defined as
      objects with less-self-relevant familiarity), and UNFAMILIAR (others' objects).
      The participants' task was to watch the stimuli passively. Results showed that
      left-lateralized N250 activity differentiated SELF and FAMILIAR from UNFAMILIAR,
      but SELF and FAMILIAR were not differentiated. In the later time-course, SELF was
      dissociated from FAMILIAR, indicating the self-relevance effect in object
      recognition at this stage. This activity did not show consistent lateralization,
      in contrast to previous studies reporting right lateralization in self-relevant
      face and name recognition. We concluded that in object recognition, self
      relevance was processed by higher-order cognitive functions later than 300ms
      after stimulus onset.

PMID- 17223241
TI  - Psychiatry and political-institutional abuse from the historical perspective: the
      ethical lessons of the Nuremberg Trial on their 60th anniversary.
AB  - Sixty years ago at the Nuremberg Trials, 23 Nazi leaders were tried as war
      criminals, in what was known as "The Doctors' Trial". This trial exposed a
      perverse system of the criminal use of medicine in the fields of public health
      and human research. These practices, in which racial hygiene constituted one of
      the fundamental principles and euthanasia programmes were the most obvious
      consequence, violated the majority of known bioethical principles. Psychiatry
      played a central role in these programmes, and the mentally ill were the
      principal victims. The aim of the present work is to review, from the historical
      perspective, the antecedents of the shameful euthanasia programmes for the
      mentally ill, the procedures involved in their implementation and the use of
      mentally ill people as research material. The Nuremberg Code, a direct
      consequence of the Doctors' Trial, is considered to be the first international
      code of ethics for research with human beings, and represented an attempt to
      prevent any repeat of the tragedy that occurred under Nazism. Nevertheless, the
      last 60 years have seen continued government-endorsed psychiatric abuse and
      illegitimate use of psychoactive drugs in countries such as the Soviet Union or
      China, and even in some with a long democratic tradition, such as the United
      States. Even today, the improper use of psychiatry on behalf of governments is
      seen to be occurring in numerous parts of the globe: religious repression in
      China, enforced hospitalization in Russia, administration of psychoactive drugs
      in immigrant detention centres in Australia, and the application of the death
      penalty by lethal injection and psychiatric participation in coercive
      interrogation at military prisons, in relation to the USA. The Declaration of
      Madrid in 1996 constituted the most recent attempt to eradicate, from the ethical
      point of view, these horrendous practices. Various strategies can be used to
      combat such abuses, though it is uncertain how effective they are in preventing
      them.

PMID- 17223242
TI  - Gender differences of acute and chronic administration of dehydroepiandrosterone
      in rats submitted to the forced swimming test.
AB  - Previous pre-clinical and clinical studies investigating the antidepressant
      potential of DHEA revealed conflicting results. In this study, the effects of
      exogenous DHEA on performance in the forced swimming test (FST) were examined in
      male and female Wistar rats in different phases of the estrous cycle.
      Furthermore, the effects of treatment and of the FST, on corticosterone and DHEA
      serum levels were investigated. Acute administration of DHEA (2 mg/kg)
      significantly increased freezing only in proestrus female rats. Similarly, the
      chronic administration of DHEA (2 mg/kg) increased freezing duration and
      decreased climbing behavior but only in females in diestrus II compared to those
      given vehicle. These results demonstrate that chronically administered DHEA
      induces a depressant-like effect, and this effect is sex dependent. There was no
      direct correlation between corticosterone levels or the corticosterone/DHEA ratio
      and the behaviors studied. After the FST, serum DHEA and corticosterone levels
      were increased, with females showing higher DHEA levels than males. Nevertheless,
      corticosterone levels were unaltered with chronic procedure; an effect that was
      independent of sex and treatment. These findings are relevant for research
      examining alternative treatment for depression and may elucidate the gender
      differences involved in stress-related diseases.

PMID- 17223243
TI  - The role of ROS in microcystin-LR-induced hepatocyte apoptosis and liver injury
      in mice.
AB  - Microcystin-LR (MC-LR) produced by cyanobacteria in diverse water systems is a
      potent specific hepatotoxin and has been documented to induce hepatocyte
      apoptosis and liver injury; however, the mechanisms have not been fully
      elucidated. In the present study, we investigated whether MC-LR stimulated ROS
      generation in the liver of mice and the role of ROS in the pathogenesis of MC-LR
      induced liver injury in vivo. MC-LR treatment (60 microg/kg of body weight) for
      12h prompted large amount of ROS generation in mice liver, upregulated the
      expression of Bax and Bid, caused the mitochondrial membrane potential (MMP) loss
      and hepatocyte apoptosis as well as liver injury. While pretreatment with
      antioxidants, oral administration of vitamin C (250mg/kg of body weight,
      dissolved in double distill water) and vitamin E (200mg/kg of body weight,
      dissolved in corn oil) per day for 3 days continually, significantly reduced the
      generation of ROS and effectively inhibited the MC-LR-induced hepatocyte
      apoptosis and liver injury, suggesting that ROS played a critical role in MC-LR
      induced hepatocyte apoptosis and liver injury. The protective effect of vitamin C
      and E also suggested the potential interest in the clinical treatment of MC-LR
      induced liver injury and hepatotoxicity.

PMID- 17223244
TI  - Downregulation of NF-kappaB activation in a H4IIE transfectant insensitive to
      doxorubicin-induced apoptosis.
AB  - Cytostatic drugs are administered to cancer patients in order to drive the tumor
      cells into apoptosis by DNA damage signalling pathway(s). DNA damage also leads
      to NF-kappaB activation, and it is controversial whether this is exclusively part
      of a survival process, thus enabling drug resistance, or whether it can also lead
      to a pro-apoptotic response, thus supporting the therapeutic purpose of drug
      administration. In the present work, the pathway and outcome of NF-kappaB
      activation was compared in the doxorubicin sensitive H4IIE rat hepatoma cell and
      the H4IIE-derived transfectant Yv2-12 which is insensitive to doxorubicin induced
      apoptosis. In the wild type H4IIE cell, doxorubicin induces serine 536
      phosphorylation and nuclear translocation of p65 which however results in reduced
      rather than increased expression of the anti-apoptotic protein XIAP. Apoptosis in
      H4IIE cells is accompanied by rapid production of intracellular reactive oxygen
      species, caspase activation and increased expression of the pro-apoptotic protein
      Bax. The doxorubicin-insensitive Yv2-12 transfectant differs from its wild type
      counterpart by the complete failure to activate NF-kappaB in response to
      doxorubicin. In contrast, serine 536 phosphorylation and nuclear translocation of
      p65 are even reduced by doxorubicin treatment while the expression of XIAP and
      Bax remain virtually unchanged. These results show that NF-kappaB activation by
      doxorubicin in our experimental system proceeds by an atypical pathway resulting
      in a pro-apoptotic effect and that insensitivity to doxorubicin-induced apoptosis
      was accompanied by a loss of NF-kappaB activation.

PMID- 17223245
TI  - The impact of manual defibrillation technique on no-flow time during simulated
      cardiopulmonary resuscitation.
AB  - INTRODUCTION: Rapid defibrillation is the most effective strategy for
      establishing return of spontaneous circulation following cardiac arrest due to
      ventricular fibrillation. The aim of this study is to measure the delay due to of
      charging the defibrillator during chest compression in an attempt to reduce the
      duration of the pre-shock pause in between cessation of chest compressions and
      shock delivery as advocated by the American Heart Association (AHA) guidelines
      compared to charging the defibrillator immediately following rhythm analysis
      without resuming chest compressions as recommended by the European Resuscitation
      Council (ERC). METHODS: This was a randomised controlled cross over trial
      comparing pre-shock pause times when defibrillation was performed on a manikin
      according to the AHA and ERC guidelines using paddles and hands free
      defibrillation systems. RESULTS: The pre-shock pause between cessation of chest
      compression and shock delivery was significantly different between techniques
      (Friedman test, P<0.0001). ERC paddles technique had the greatest pre-shock pause
      (7.4 s [6.7-11.2]) followed by ERC hands free (7.0 s [6.5-8.5]) and AHA paddles
      (1.6 s [1.1-2.3]). AHA hands free took the least amount of time (1.5 s [0.8
      1.5]). Extrapolating these data to older defibrillators with longer charge times
      saw pre-shock pause intervals of 9 s (Codemaster XL) and 12 s (Lifepak 20) with
      the ERC approach. CONCLUSION: This study demonstrated clinically significant
      delays to defibrillation by analysing and charging the defibrillator without
      performing concurrent chest compressions. In a simulated scenario, charging the
      defibrillator whilst performing chest compressions was perceived as safe and
      significantly reduced the pre-shock pause between cessation of chest compression
      and shock delivery.

PMID- 17223246
TI  - Association of delay to first intervention with return of spontaneous circulation
      in a swine model of cardiac arrest.
AB  - OBJECTIVE: No single drug improves survival after cardiac arrest, despite success
      in animal studies. We sought to determine the duration of circulatory arrest
      after which maximal drug treatment and a rescue shock would fail to achieve
      return of spontaneous circulation (ROSC). DESIGN/SUBJECTS: Retrospective analysis
      of 271 swine (20-30 kg) resuscitation attempts during ventricular fibrillation.
      Protocols were divided into five categories: immediate countershock,
      cardiopulmonary resuscitation (CPR) with standard-dose drugs, CPR alone, CPR and
      high-dose epinephrine (CPR+HDE) (0.1 mg/kg), and CPR with a drug cocktail
      (CPR+DC) of propanolol (1 mg), epinephrine (adrenaline) (0.1 mg/kg) and
      vasopressin (40IU). Time to first CPR, time to first drug administration, time to
      first shock, and protocol were examined as predictors of ROSC using logistic
      regression with Hosmer-Lemeshow test of fit. Probability of ROSC was calculated
      from logistic curves. MAIN RESULTS: ROSC occurred in 119 of the 271 swine (44%).
      Time to first drug and the CPR+DC group were predictors of ROSC. Time to first
      CPR, the CPR+DC group, and the CPR+HDE group were also predictors of ROSC. Time
      to first rescue shock, the CPR+DC group, and the CPR+HDE groups were predictors
      of ROSC. In the CPR+DC group, 50% ROSC occurred at a first CPR time of 13.4 min,
      first drug time of 14.1 min and first rescue shock time of 17.5 min. CONCLUSIONS:
      Pre-shock delivery of CPR+DC increases the likelihood of ROSC, and reaches 50%
      with a time of drug delivery of 14.1 min. ROSC rates of 50% may be achievable
      using an optimized resuscitation in experimental CPR.

PMID- 17223247
TI  - Long-term neurodevelopmental outcome of triplets.
AB  - OBJECTIVE: To analyze the incidence of neurodevelopmental disabilities in
      triplets and to find out possible connection between the outcome and perinatal
      events. DESIGN: Retrospective cohort study of 94 triplets and their outcome at 24
      144 months of age correlated with gestational age, birth weight, pregnancy
      complications, early neonatal period, neonatal cranial ultrasound, period of
      birth (1985-1995, 1996-2000) and type of antenatal care. RESULTS: Sixty-two
      triplets are healthy, 15 suffer cerebral palsy (CP) and 17 minimal cerebral
      dysfunction (MCD). Adverse outcome correlates significantly with prematurity, low
      birth weight and maternal age. In multivariate analysis, both cerebral palsy and
      minor disabilities correlate significantly with early neonatal complications,
      neonatal cranial ultrasound with later CP (p<0.01), and MCD with preterm rupture
      of membranes (p=0.047). Children conceived spontaneously do worse than those born
      after assisted reproduction (p=0.004), those born in the time period 1996-2000 do
      better than those born before (p=0.021). Seventy-seven percent (77%) of newborns
      delivered in the time period 1996-2000 and after level 1 antenatal care was
      introduced, compared with 54% being delivered in the time period before 1996 and
      with less meticulous types of antenatal care, remain healthy (p=0.015).
      CONCLUSION: Triplets are still at high risk for long-term neurodevelopmental
      complications. Stringent perinatal care might appear important determinant of
      their long-term outcome.

PMID- 17223248
TI  - Evaluation of groundwater contamination beneath an urban environment: the Besos
      river basin (Barcelona, Spain).
AB  - The urban groundwater of the central Besos river basin (the La Llagosta aquifer)
      has become contaminated due to the infiltration of wastewater from septic tanks
      and sewage networks, and by industrial activities located in urban areas. The
      groundwater hydrogeochemistry of the La Llagosta aquifer was characterized using
      isoconcentration maps, hydrogeochemical diagrams (Piper, Schoeller-Berkaloff) and
      by analyzing hydrogeochemical changes along a flow-path that crosses an urban and
      peripheral industrial area in the main alluvial aquifer (the La Llagosta unit).
      The evolution of cations, anions and heavy metals along the flow path and the use
      of the PHREEQC numerical code indicate a complex set of geochemical processes,
      which result from the interaction between the sources of pollution, the
      groundwater flow and the mineral composition of the aquifer materials. The
      contaminated groundwater below the urban areas shows high contents of NO(3)(-)
      (90-100 mg/L) and an increase in the concentrations of Ca(2+) and Mg(2+) which
      coincides with a decrease in pH. The Eh shows greater variation than the pH along
      the flow line studied, with values ranging between 56 mV in the industrial area
      and 370 mV in the urban area. The area with the lowest Eh value coincides with
      the highest concentrations of dissolved Fe (4.7 mg/L) and Mn (0.22 mg/L).

PMID- 17223249
TI  - Anaerobic-aerobic treatment of purified terephthalic acid (PTA) effluent; a
      techno-economic alternative to two-stage aerobic process.
AB  - This paper addresses the treatment of purified terephthalic acid (PTA) effluent
      using anaerobic and aerobic processes. Laboratory studies were carried out on
      flow proportionate composite wastewater generated from the manufacturing of PTA.
      An activated sludge process (ASP-two stage and single stage) and an upflow
      anaerobic fixed film fixed bed reactor (AFFFBR) were used, individually and in
      combination. The performance of a full-scale ETP under existing operating
      conditions was also studied. Full scale ETP studies revealed that the treatment
      of PTA effluent using a two-stage ASP alone does not meet treated effluent
      quality within the prescribed Indian Standards. The biomass produced in the two
      stage ASP was very viscous and fluffy and the sludge volume index (SVI) was very
      high (200-450 ml/g). However, pretreatment of PTA effluent using an upflow AFFFBR
      ensured substantial reduction in BOD (63%) and COD (62%) with recovery of biogas
      at 1.8-1.96 l/l effluent treated at a volumetric loading rate (VLR) 4-5 kg
      COD/m(3) d. The methane content in the biogas varied between 55% and 60%. The
      pretreated effluent from the upflow AFFFBR was then treated through a single
      stage ASP. The biomass produced in the ASP after anaerobic treatment had very
      good settlability (SVI: 75-90 ml/g) as compared to the two stage ASP and the
      treated effluent quality with respect to BOD, COD and SS was within the
      prescribed Indian Standards. The alternative treatment process comprising an
      upflow AFFFBR and a single stage ASP ensured net power saving of 257 kW and in
      addition generated 442 kW of power through the AFFFBR.

PMID- 17223250
TI  - Recommendations on the safe use of ultrasound contrast agents.

PMID- 17223251
TI  - WFUMB Safety Symposium on Echo-Contrast Agents: mechanisms for the interaction of
      ultrasound.

PMID- 17223252
TI  - WFUMB Safety Symposium on Echo-Contrast Agents: in vitro bioeffects.

PMID- 17223253
TI  - WFUMB Safety Symposium on Echo-Contrast Agents: nature and types of ultrasound
      contrast agents.

PMID- 17223254
TI  - Lexicon of terms.

PMID- 17223255
TI  - Identification of the molecular switch that regulates access of 5alpha-DHT to the
      androgen receptor.
AB  - Pairs of hydroxysteroid dehydrogenases (HSDs) govern ligand access to steroid
      receptors in target tissues and act as molecular switches. By acting as
      reductases or oxidases, HSDs convert potent ligands into their cognate inactive
      metabolites or vice versa. This pre-receptor regulation of steroid hormone action
      may have profound effects on hormonal response. We have identified the HSDs
      responsible for regulating ligand access to the androgen receptor (AR) in human
      prostate. Type 3 3alpha-hydroxysteroid dehydrogenase (aldo-keto reductase 1C2)
      acts solely as a reductase to convert 5alpha-dihydrotestosterone (DHT), a potent
      ligand for the AR (K(d)=10(-11)M for the AR), to the inactive androgen 3alpha
      androstanediol (K(d)=10(-6)M for the AR); while RoDH like 3alpha-HSD (a short
      chain dehydrogenase/reductase (SDR)) acts solely as an oxidase to convert 3alpha
      androstanediol back to 5alpha-DHT. Our studies suggest that aldo-keto reductase
      (AKRs) and SDRs function as reductases and oxidases, respectively, to control
      ligand access to nuclear receptors.

PMID- 17223256
TI  - Regulation of SOCS-3 expression by leptin and its co-localization with insulin
      receptor in rat skeletal muscle cells.
AB  - Obesity is a well-defined risk factor for the development of insulin resistance
      in target tissues, such as skeletal muscle, and thus type 2 diabetes. This may
      occur due to endocrine effects mediated by adipokines including leptin, the
      product of the obese (ob) gene, whose circulating levels positively correlate
      with body mass index. Induction of suppressor of cytokine-3 (SOCS-3) protein
      expression has been implicated as a possible mechanism of leptin-induced insulin
      resistance. Here, we show that treatment of rat skeletal muscle cells with leptin
      activated the SOCS-3 gene promoter and caused a time-dependent increase in both
      SOCS-3 mRNA and protein content. Confocal microscopy demonstrated increased co
      localization of SOCS-3 with insulin receptor in leptin-treated cells and we
      confirmed a direct interaction between these two proteins by showing increased
      coimmunoprecipitation of SOCS-3 and insulin receptor after exposure of cells to
      leptin. However, the expected functional consequences were not observed, as we
      saw no change in basal or insulin-stimulated glucose uptake and phosphorylation
      of GSK3beta, Akt (T308 and S473) or ERK1/2. In summary, leptin induced SOCS-3
      expression and its association with the insulin receptor in rat skeletal muscle
      cells but functional significance of this increase was not apparent upon
      measuring glucose uptake.

PMID- 17223257
TI  - Camptothecin acts synergistically with imatinib and overcomes imatinib resistance
      through Bcr-Abl independence in human K562 cells.
AB  - In this study, we have tried to find new targets and effective drugs for imatinib
      resistant chronic myelogenous leukemia (CML) cells displaying loss of Bcr-Abl
      kinase target dependence. The imatinib-resistant K562/R1, -R2 and -R3 cells
      showed profound declines of Bcr-Abl level and concurrently exhibited up
      regulation of Bcl-2 and Ku70/80, and down-regulation of Bax, DNA-PKcs and BRCA1,
      suggesting that loss of Bcr-Abl after exposure to imatinib might be accompanied
      by other cell survival mechanism. K562/R3 cells were more sensitive to
      camptothecin (CPT)- and radiation-induced apoptosis than K562 cells, indicating
      hypersensitivity of imatinib-resistant cells to DNA damaging agents. Moreover,
      when K562 cells were treated with the combination of imatinib with CPT, the level
      of Bax and the cleavage of PARP-1 and DNA-PK were significantly increased in
      comparison with the effects of each drug. Therefore, our study suggests that CPT
      can be used to treat CML with loss of Bcr-Abl expression.

PMID- 17223258
TI  - Genome-wide single nucleotide polymorphism analysis of lung cancer risk detects
      the KLF6 gene.
AB  - A genome-wide association analysis using the Affymetrix 100K SNP array was
      carried out in a case-control study of lung cancer. Allele frequencies were
      estimated initially in DNA pools. Significant differences in allele frequency
      detected in the SNP array analysis were first tested in the same DNA pools by
      pyrosequencing and then by individual genotyping. DNA pooling analysis identified
      rs10508266 SNP, located approximately 12.5kb from the 5'-end of the KLF6 gene, as
      a marker showing significant association with lung cancer risk. Since the SNP was
      in significant linkage disequilibrium with the KLF6 gene region, we analyzed an
      Italian population of 338 lung adenocarcinoma cases and 335 controls for the
      possible role of the reported functional rs3750861 SNP, located 15.6kb from the
      rs10508266 SNP. The rs3750861 affects expression of KLF6 splicing variants in
      prostate cancer and we found that its rare allele is associated with reduced lung
      cancer risk (odds ratio, 0.5; 95% CI, 0.3-0.8). A Norwegian replication series of
      265 non small cell lung cancer cases, and 356 controls, however, did not confirm
      the association. In light of the reported functional involvement of the KLF6 gene
      in lung cancer and in other cancer types and to the functional nature of the
      rs3750861 SNP, our results suggest a potential involvement of KLF6 polymorphisms
      in lung cancer risk, although additional studies in large series are needed to
      confirm our findings and to elucidate the mechanism by which the KLF6 SNPs
      influence lung cancer risk.

PMID- 17223259
TI  - In vitro and in vivo anti-tumor effects of Astragalus membranaceus.
AB  - Astragalus membranaceus, a commonly used Chinese medicinal plant, has been shown
      to be capable of restoring the impaired T cell functions in cancer patients. In
      this study, the in vitro and in vivo anti-tumor effects of A. membranaceus were
      investigated. Five bioactive fractions were isolated from the root of A.
      membranaceus, the fraction designated as AI was found to be the most potent among
      the five fractions with respect to its mitogenicity on murine splenocytes.
      Besides investigating the cytostatic effect of AI, its activities on macrophage
      function, tumor necrosis factor production, induction of lymphokine-activated
      killer cell and tumor cell differentiation were also examined. The macrophage
      like tumors and the myeloid tumors were found to be more sensitive to the
      cytostatic activity of AI, whereas the fibroblast-like tumors and the mouse
      Ehrlich ascites tumor appeared to be relatively resistant. Moreover, AI could
      effectively suppress the in vivo growth of syngeneic tumor in mice. Results
      showed that murine macrophage pretreated with AI had increased in vitro and in
      vivo cytostatic activities towards MBL-2 tumor. AI could also act as a priming
      agent for tumor necrosis factor production in tumor-bearing mice. Preincubation
      of mouse splenocytes with AI could induce in vitro lymphokine-activated killer
      like activity towards WEHI-164 cell. Furthermore, AI was able to induce monocytic
      differentiation of both human and murine cells in vitro. AI administered in vivo
      could even partially restore the depressed mitogenic response in tumor-bearing
      mice. Collectively, the results showed that A. membranaceus could exhibit both in
      vitro and in vivo anti-tumor effects, which might be achieved through activating
      the anti-tumor immune mechanism of the host.

PMID- 17223260
TI  - Solid-phase extraction of Mn(II), Co(II), Ni(II), Cu(II), Cd(II) and Pb(II) ions
      from environmental samples by flame atomic absorption spectrometry (FAAS).
AB  - A new method using a column packed with Amberlite XAD-2010 resin as a solid-phase
      extractant has been developed for the multi-element preconcentration of Mn(II),
      Co(II), Ni(II), Cu(II), Cd(II), and Pb(II) ions based on their complex formation
      with the sodium diethyldithiocarbamate (Na-DDTC) prior to flame atomic absorption
      spectrometric (FAAS) determinations. Metal complexes sorbed on the resin were
      eluted by 1 mol L(-1) HNO3 in acetone. Effects of the analytical conditions over
      the preconcentration yields of the metal ions, such as pH, quantity of Na-DDTC,
      eluent type, sample volume and flow rate, foreign ions etc. have been
      investigated. The limits of detection (LOD) of the analytes were found in the
      range 0.08-0.26 microg L(-1). The method was validated by analyzing three
      certified reference materials. The method has been applied for the determination
      of trace elements in some environmental samples.

PMID- 17223261
TI  - Gliding arc plasma processing of CO2 conversion.
AB  - Conversion of carbon dioxide (CO2) using gliding arc plasma was performed. The
      research was done to investigate the effect of variation of total gas flow rates
      and addition of auxiliary gases--N2, O2, air, water--to the CO2 conversion
      process. This system shows higher power efficiency than other nonthermal plasma
      methods. Experiment results indicate the conversion of CO2 reaches 18% at total
      gas flow rate of 0.8 L/min and produces CO and O2 as the main gaseous products.
      Among auxiliary gases, only N2 gives positive effect on CO2 conversion and the
      power efficiency at N2 concentration of 95% and total gas flow rate of 2 L/min
      increases about three times compared to pure CO2 process.

PMID- 17223262
TI  - Comparison of linear and nonlinear analysis in estimating the Thomas model
      parameters for methylene blue adsorption onto natural zeolite in fixed-bed
      column.
AB  - Comparison analysis of linear least square method and nonlinear least square
      method for estimating the kinetic parameters was made using the experimental
      column data of methylene blue (MB) adsorption onto zeolite at different flow
      rates and initial concentration. The data were fitted to Thomas model equations
      using linear and nonlinear regressive analysis, respectively. The error analysis
      was performed. Present investigation showed that the linear and nonlinear methods
      are both suitable to predict the breakthrough curves using Thomas model
      parameters and the nonlinear method is better.

PMID- 17223263
TI  - Photodegradation of norfloxacin in aqueous suspensions of titanium dioxide.
AB  - The photocatalytic degradation of an antibiotic norfloxacin [1-ethyl-6-fluoro-1,4
      dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline-carboxylic acid, 1], has been
      investigated in aqueous suspensions of titanium dioxide (TiO(2)) under a variety
      of conditions. The degradation was studied by monitoring the change in substrate
      concentration employing UV spectroscopic analysis technique and depletion in
      total organic carbon (TOC) content as a function of irradiation time. The
      degradation kinetics were investigated under different conditions such as
      different types of TiO(2), pH (ranging from 4 to 11), catalyst concentration (0.5
      3gL(-1)), substrate concentration (0.15-0.5mM) and in the presence of electron
      acceptor such as hydrogen peroxide (H(2)O(2), 10mM) besides molecular oxygen.
      Semiconductor titanium dioxide (Degussa P25) was found to be more efficient as
      compared with other photocatalysts.

PMID- 17223265
TI  - Mismatch negativity on the cone of confusion.
AB  - Localization of sounds by the auditory system is based on the analysis of three
      sources of information: interaural level differences (ILD, caused by an
      attenuation of the sound as it travels to the more distant ear), interaural time
      differences (ITD, caused by the additional amount of time it takes for the sound
      to arrive at the more distant ear), and spectral cues (caused by direction
      specific spectral filter properties of the pinnae). Although in a number of
      psychophysiological studies cortical processes of ITD and ILD analysis were
      investigated, there is hitherto no evidence on the cortical processing of
      spectral cues for sound localization. The objective of the present experiment was
      to test whether it is possible to observe electrophysiological correlates of
      sound localization based on spectral cues. In an auditory oddball experiment, 80
      ms of broadband noise from varying free field locations were presented to
      inattentive participants. Mismatch negativities (MMNs) were observed for pairs of
      standards and location deviants located symmetrically with respect to the
      interaural axis. As interaural time and level differences are identical for such
      pairs of sounds, the observed MMNs most likely reflect cognitive processes of
      sound localization utilizing the spectral filter properties of the pinnae. MMN
      latencies suggest that sound localization based on spectral cues is slower than
      ITD- or ILD-based localization.

PMID- 17223264
TI  - Kainic acid induces early and transient autophagic stress in mouse hippocampus.
AB  - Kainic acid (KA) treatment is a well-established model of hippocampal neuron
      death mediated in large part by KA receptor-induced excitotoxicity. KA-induced,
      delayed neuron death has been shown previously to follow the induction of
      seizures and exhibit characteristics of both apoptosis and necrosis. Growing
      evidence supports a role of autophagic stress-induced death of neurons in several
      in vitro and in vivo models of neuron death and neurodegeneration. However,
      whether autophagic stress also plays a role in KA-induced excitotoxicity has not
      been previously investigated. To examine whether KA alters the levels of proteins
      associated with or known to regulate the formation of autophagic vacuoles, we
      isolated hippocampal extracts from control mice and in mice following 2-16 h KA
      injection. KA induced a significant increase in the amount of LC3-II, a specific
      marker of autophagic vacuoles, at 4-6h following KA, which indicates a transient
      induction of autophagic stress. Levels of autophagy-associated proteins including
      ATG5 (conjugated to ATG12), ATG6 and ATG7 did not change significantly after
      treatment with KA. However, ratios of phospho-mTOR/mTOR were elevated from 6 to
      16 h, and ratios of phospho-Akt/Akt were elevated at 16 h following KA treatment,
      suggesting a potential negative feedback loop to inhibit further stimulation of
      autophagic stress. Together these data indicate the transient induction of
      autophagic stress by KA which may serve to regulate excitotoxic death in mouse
      hippocampus.

PMID- 17223266
TI  - Inhibition of Abeta production by NF-kappaB inhibitors.
AB  - The transcription factor nuclear factor kappaB (NF-kappaB) is widely expressed in
      the nervous system and increased NF-kappaB immunoreactivity has been observed in
      Alzheimer's disease (AD) brains in the nuclei of neurons within the vicinity of
      diffuse beta-amyloid plaques. Beta-amyloid (Abeta) peptides are the main
      constituent of senile plaques and are known to stimulate NF-kappaB activity. In
      the present study, we investigated the effect of various NF-kappaB inhibitors on
      the production of Abeta1-40, Abeta1-42, secreted APP (sAPPbeta and sAPPalpha) and
      APP C-terminal fragments (APP-CTF) using CHO cells overexpressing the beta
      amyloid precursor protein (APP). Our data show that NF-kappaB inhibitors decrease
      both Abeta1-40 and Abeta1-42 production. In addition, we show that some NF-kappaB
      inhibitors decrease sAPPbeta and APP-CTFbeta suggesting that they reduce the beta
      secretase cleavage of APP. Altogether our data suggest that NF-kappaB inhibitors
      may be of therapeutic importance for the treatment of AD pathology not only by
      blocking inflammatory processes but also by directly inhibiting the production of
      Abeta peptides.

PMID- 17223268
TI  - Contribution of electron precession to the identification of the space group from
      microdiffraction patterns.
AB  - In a previous study, it was reported that the possible space groups of a crystal
      can be identified at a microscopic or nanoscopic scale, thanks to
      microdiffraction patterns obtained with a nearly parallel electron incident beam
      focused on a very small area of the specimen. A systematic method was proposed,
      which consists of the observation of a few microdiffraction patterns displaying
      at least two Laue zones. These microdiffraction patterns can also be obtained by
      using an electron precession equipment. In this case, the patterns display a very
      large number of reflections in the Laue zones whose intensity is the integrated
      intensity. These original features greatly facilitate the space group
      identification method and are particularly useful when the high-order Laue zones
      (HOLZ) are not visible on microdiffraction patterns or when very thin specimens
      are not available.

PMID- 17223267
TI  - Tyrosine phosphorylation of rabphilin during long-lasting long-term potentiation.
AB  - Long-term potentiation (LTP) is a persistent increase in the strength of synaptic
      transmission triggered by neuronal activity. Here, we submitted hippocampal
      slices to a perfusion of forskolin and IBMX, which induces a long-lasting LTP (>4
      h) (L-LTP). We separated the proteins of the CA1 region by two-dimensional gel
      electrophoresis (2-DE). We then immunoblotted them using an anti-p-Tyr antibody.
      We found a protein whose tyrosine phosphorylation was unchanged 10 min after LTP
      induction but was dramatically increased after 1h, dropping back to its baseline
      after 4 h. This protein was identified as rabphilin using matrix-assisted laser
      desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS). We also
      demonstrated that genistein, an inhibitor of tyrosine phosphorylation, prevented
      the development of the late phase of electrically-induced L-LTP. Our results
      suggest that rabphilin, a protein present in presynaptic terminals, could play a
      role in the late phase of L-LTP.

PMID- 17223269
TI  - Prevalence and intensity of intestinal helminths found in free-ranging golden
      lion tamarins (Leontopithecus rosalia, Primates, Callitrichidae) from Brazilian
      Atlantic forest.
AB  - Helminth identification and egg counts were performed in 316 fecal samples during
      4 years in 199 golden lion tamarins (GLTs), Leontopithecus rosalia, from two
      Brazilian conservation units. Tamarin sex and age, area of occurrence and
      helminth co-infection were tested as potential factors that could affect helminth
      prevalence and egg shedding in host individuals. Three nematodes species were
      found at low prevalences but not in both conservation units: Ancylostomatidae
      (12%), Ascarididae (1%) and Tripanoxyuris minutus, an Oxyuridae (4%). Three other
      species had high prevalences and were found in both conservation units: one
      acanthocephalan, Oncicola sp. (30%), and two nematodes, Spiruridae (24%), and
      Trichostrongylidae (31%). These three latter helminths had distinct prevalences
      between the conservation units, probably due to differences in availability of
      helminth infective stages in each area. Prevalences were greater in females for
      all helminth species; this was especially the case for Oncicola sp. Sex and age
      differences in helminth prevalence may be associated with changes in sexual
      steroid levels that accompany age and reproductive status. Frequency of
      simultaneous infections by the two helminths considered most pathogenic (Oncicola
      and Trichostrongylidae) were statistically lower than expected; this may be
      related to: (i) higher tamarin death rate caused by the association; (ii)
      differences in exposure to helminth infective stages in the various areas of
      occurrence; (iii) and competition between these helminth species. All helminth
      species followed a negative binomial distribution, with stronger clumping
      occurring in Trichostrongylidae and in female GLTs. Distinct transmission
      strategies of Oncicola sp. and Spiruridae, in contrast with Trichostrongylidae,
      may partially explain the different clumping levels of these helminths in GLTs.
      Mean fecal egg counts of all helminths were not different between GLT sexes, ages
      or areas of occurrence. The three most common helminth species may be a threat to
      isolated or dense GLT populations.

PMID- 17223270
TI  - Evaluation of four serological techniques to determine the seroprevalence of
      Neospora caninum in foxes (Vulpes vulpes) and coyotes (Canis latrans) on Prince
      Edward Island, Canada.
AB  - The objectives of this study were (1) to evaluate the performance and agreement
      of serological assays (ELISA, IFAT, Neospora caninum agglutination test and
      immunoblot) using reference sera and field sera from foxes and coyotes and (2) to
      estimate the N. caninum seroprevalence in foxes and coyotes on Prince Edward
      Island, Canada. With fox and coyote reference sera the test performance of the
      ELISA, IFAT and IB was excellent (100% sensitivity and specificity). NAT showed a
      low sensitivity (50%). Serum was collected from 201 coyotes and 271 foxes. The
      seroprevalence observed in the different assays ranged from 0.5 to 14.0% in
      coyotes and 1.1 to 34.8% in foxes. The seroprevalence, when taking more than one
      test positive as cut-off value was 3.3 and 1.1% for coyotes and foxes,
      respectively. From the N. caninum-positive group, all coyotes were older than 3
      years. Agreement among assays (measured as prevalence-adjusted bias-adjusted
      kappa) using the field sera ranged from 0.17 to 0.97. Best agreement was observed
      between ELISA and IFAT, poor agreement was observed between NAT and the other
      assays. Positive agreement was moderate to poor among all assays utilized in this
      study. Although the seroprevalence observed was low, N. caninum antibodies are
      present in foxes and coyotes on Prince Edward Island (PEI) and their role in the
      N. caninum epidemiology needs further study.

PMID- 17223271
TI  - The effect of ultrasound on flap survival: an experimental study in rats.
AB  - BACKGROUND: Ultrasound is commonly used by physical therapists, but there is no
      consensus regarding the most effective therapeutic dose for accelerating healing
      of open or closed wounds. Now, the effect of therapeutic ultrasound on the
      formation of new blood vessels in full-thickness excised lesions in the flank
      skin of adult rats has been assessed quantitatively using microfocal X-ray
      techniques. METHODS: To investigate this, 30 rats were divided into three groups
      of 10 animals: a control group and two treated with ultrasound groups. Random
      dorsal skin flaps were elevated on the rats. In the control group, no operative
      procedures agents were used. Of the two treated groups, group 1 were exposed to
      pulsed ultrasound (2 ms on, 8 ms off) at an intensity of 0.1 W cm(-2) SATA
      (frequency either 0.75 MHz or 3.0 MHz). Group 2 exposed to pulsed ultrasound (2
      ms on, 8 ms off) at an intensity of 0.18 W cm(-2) SATA (frequency either 0.75 MHz
      or 3.0 MHz), respectively. RESULTS: The areas of flap necrosis were measured in
      each group. The median lengths of flap necrosis of the groups were 79.3, 57.0,
      and 35.3 mm, respectively. There was a statistically significant improvement of
      flap necrosis in ultrasound-treated groups compared with the control group (group
      2, p=0.001; group 3, p=0.001). Furthermore, there was less necrosis in the high
      intensity ultrasound-treated group than the low intensity-treated group.
      CONCLUSION: Ultrasound may have an intensity-dependent effect to increase flap
      survival in random skin flaps.

PMID- 17223272
TI  - Ascorbic acid increases healing of excision wounds of mice whole body exposed to
      different doses of gamma-radiation.
AB  - Because of the practical importance of acute radiation exposure associated with
      combined injuries, it is imperative to investigate the efficacy of cost-effective
      nutritional factors in the reconstruction of irradiated wounds. Therefore, effect
      of pretreatment of ascorbic acid was studied on the healing of excised wounds in
      mice exposed to 2, 4, 6 and 8 Gy whole body gamma-radiation. A full-thickness
      wound was created on the dorsum of the irradiated mice and the progression of
      wound contraction was monitored by capturing video images of the wound at various
      varying days after irradiation. Irradiation caused a dose dependent delay in
      wound contraction and wound healing time, while ascorbic acid pretreatment
      resulted in a significant acceleration in the rate of wound contraction and a
      decrease in the mean wound healing time. To understand the mechanism of healing,
      collagen, hexosamine, DNA, nitrite and nitrate contents were measured in the
      granulation tissue of wounded mice treated with ascorbic acid before exposure to
      6 Gy gamma-radiation. Ascorbic acid treatment prior to irradiation enhanced the
      synthesis of collagen, hexosamine, DNA, nitrite and nitrate contents. The
      histological assessment of wound biopsy revealed an improved collagen deposition,
      and increase in fibroblast and vascular densities. The present study demonstrates
      that ascorbic acid pretreatment has a beneficial effect on the irradiated wound
      and could be a substantial therapeutic strategy to accelerate wound repair in
      irradiated wounds and in the cases of combined injury situations.

PMID- 17223273
TI  - Neurotrophic modulation of myelinated cutaneous innervation and mechanical
      sensory loss in diabetic mice.
AB  - Human diabetic patients often lose touch and vibratory sensations, but to date,
      most studies on diabetes-induced sensory nerve degeneration have focused on
      epidermal C-fibers. Here, we explored the effects of diabetes on cutaneous
      myelinated fibers in relation to the behavioral responses to tactile stimuli from
      diabetic mice. Weekly behavioral testing began prior to streptozotocin (STZ)
      administration and continued until 8 weeks, at which time myelinated fiber
      innervation was examined in the footpad by immunohistochemistry using antiserum
      to neurofilament heavy chain (NF-H) and myelin basic protein (MBP). Diabetic mice
      developed reduced behavioral responses to non-noxious (monofilaments) and noxious
      (pinprick) stimuli. In addition, diabetic mice displayed a 50% reduction in NF-H
      positive myelinated innervation of the dermal footpad compared with non-diabetic
      mice. To test whether two neurotrophins nerve growth factor (NGF) and/or
      neurotrophin-3 (NT-3) known to support myelinated cutaneous fibers could
      influence myelinated innervation, diabetic mice were treated intrathecally for 2
      weeks with NGF, NT-3, NGF and NT-3. Neurotrophin-treated mice were then compared
      with diabetic mice treated with insulin for 2 weeks. NGF and insulin treatment
      both increased paw withdrawal to mechanical stimulation in diabetic mice, whereas
      NT-3 or a combination of NGF and NT-3 failed to alter paw withdrawal responses.
      Surprisingly, all treatments significantly increased myelinated innervation
      compared with control-treated diabetic mice, demonstrating that myelinated
      cutaneous fibers damaged by hyperglycemia respond to intrathecal administration
      of neurotrophins. Moreover, NT-3 treatment increased epidermal Merkel cell
      numbers associated with nerve fibers, consistent with increased numbers of NT-3
      responsive slowly adapting A-fibers. These studies suggest that myelinated fiber
      loss may contribute as significantly as unmyelinated epidermal loss in diabetic
      neuropathy, and the contradiction between neurotrophin-induced increases in
      dermal innervation and behavior emphasizes the need for multiple approaches to
      accurately assess sensory improvements in diabetic neuropathy.

PMID- 17223274
TI  - A neural cell adhesion molecule-derived peptide reduces neuropathological signs
      and cognitive impairment induced by Abeta25-35.
AB  - By means of i.c.v. administration of preaggregated oligomeric beta-amyloid
      (Abeta)25-35 peptide it was possible in rats to generate neuropathological signs
      related to those of early stages of Alzheimer's disease (AD). Abeta25-35
      administration induced the deposition of endogenously produced amyloid protein.
      Furthermore, quantitative immunohistochemistry demonstrated time-related
      statistically significant increases in amyloid immunoreactivity, tau
      phosphorylation, microglial activation, and astrocytosis, and stereological
      investigations demonstrated statistically significant increased neuronal cell
      death and brain atrophy in response to Abeta25-35. Finally, the Abeta25-35
      administration led to a reduced short-term memory as determined by the social
      recognition test. A synthetic peptide termed FGL derived from the neural cell
      adhesion molecule (NCAM) was able to prevent or, if already manifest, strongly
      reduce all investigated signs of Abeta25-35-induced neuropathology and cognitive
      impairment. The FGL peptide was recently demonstrated to be able to cross the
      blood-brain-barrier. Accordingly, we found that the beneficial effects of FGL
      were achieved not only by intracisternal, but also by intranasal and s.c.
      administration of the peptide. Furthermore, FGL-treatment was shown to inhibit
      the activity of GSK3beta, a kinase implicated in signaling regulating cell
      survival, tau phosphorylation and the processing of the amyloid precursor protein
      (APP). Thus, the peptide induced a statistically significant increase in the
      fraction of GSK3beta phosphorylated on the Ser9-position, a posttranslational
      modification known to inhibit the activity of the kinase. Hence, the mode of
      action of FGL with respect to the preventive and curative effects on Abeta25-35
      induced neuropathological manifestations and cognitive impairment involves the
      modulation of intracellular signal-transduction mediated through GSK3beta.

PMID- 17223275
TI  - The relation between spike-timing dependent plasticity and Ca2+ dynamics in the
      hippocampal CA1 network.
AB  - In our previous study, spike timing dependent synaptic plasticity (STDP) was
      investigated in the CA1 area of rat hippocampal slices using optical imaging. It
      was revealed that the profiles of STDP could be classified into two types
      depending upon layer specific location along the dendrite. The first was
      characterized by a symmetric time window observed in the proximal region of the
      stratum radiatum (SR), and the second by an asymmetric time window in the distal
      region of the SR. Our methods involved the bath-application of bicuculline
      (GABA(A) receptor antagonist) to hippocampal slices, which revealed that
      GABAergic interneuron projections were responsible for the symmetry of a time
      window. In this study, the intracellular Ca2+ increase of hippocampal CA1
      neurons, induced by the protocol of timing between pre- and post-synaptic
      excitation (i.e. STDP protocol), was measured spatially by using optical imaging
      to investigate how the triggering of STDP is dependent on intracellular calcium
      concentration. We found that the magnitude of STDP was closely related to the
      rate of Ca2+ increase ("velocity") of calcium transient during application of
      induction stimuli. Location dependency was also analyzed in terms of Ca2+ influx.
      Furthermore, it was shown that decay time constant of Ca2+ dynamics during the
      application of STDP-inducing stimuli was also significantly correlated with STDP.

PMID- 17223276
TI  - Enhancement of oblique effect in the cat's primary visual cortex via orientation
      preference shifting induced by excitatory feedback from higher-order cortical
      area 21a.
AB  - It is often suggested that the oblique effect, the well-known phenomenon whereby
      both humans and animals are visually more sensitive to vertical and horizontal
      contours than to oblique ones, is due to the overrepresentation of cardinal
      orientations in the visual cortex. The functional role of feedback projections
      from higher-order cortical areas to lower-order areas is not fully understood.
      Combining the two issues in a study using optical imaging here, we report that
      the neural oblique effect was significantly enhanced (3.7 times higher than the
      normal) in the cat's primary visual cortex through orientation shifting induced
      by excitatory feedback from the higher-order cortical area 21a. This suggests
      that a reciprocal co-excitatory mechanism may underlie the perceptual oblique
      effect.

PMID- 17223277
TI  - Postsynaptic enrichment of Eps8 at dendritic shaft synapses of unipolar brush
      cells in rat cerebellum.
AB  - Epidermal growth factor receptor pathway substrate 8 (Eps8) is a widely expressed
      multidomain signaling protein that coordinates two disparate GTPase-dependent
      mechanisms: actin reorganization via Ras/Rac pathways and receptor trafficking
      via Rab5. Expression of Eps8, the gene encoding the founding member of the Eps8
      family of proteins, was found in cerebellum by virtual Northern analysis and in
      situ hybridization. Because the cerebellum has a well-known cellular architecture
      and is a favored model to study synaptic plasticity and actin dynamics, we sought
      to analyze Eps8 localization in rat cerebellar neurons and synapses by light and
      electron microscopy. Specificity of Eps8-antibody was demonstrated by immunoblots
      and in brain sections. In cerebellum, unipolar brush cells (UBCs) were densely
      Eps8 immunopositive and granule cells were moderately immunostained. In both
      types of neuron immunoreaction product was localized to the somatodendritic and
      axonal compartments. Postsynaptic immunostained foci were demonstrated in the
      glomeruli in correspondence of the synapses formed by mossy fiber terminals with
      granule cell and UBC dendrites. These foci appeared especially evident in the UBC
      brush, which contains an extraordinary postsynaptic apparatus of actin
      microfilaments facing synaptic junctions of the long and segmented varieties.
      Eps8 immunoreactivity was conspicuously absent in Purkinje cells and their actin
      rich dendritic spines, in all types of inhibitory interneurons of the cerebellum,
      cerebellar nuclei neurons, and astrocytes. In conclusion, Eps8 protein in
      cerebellum is expressed exclusively by excitatory cortical interneurons and is
      intracellularly compartmentalized in a cell-class specific manner. This is the
      first demonstration of the presence of a member of the Eps8 protein family in
      UBCs and its enrichment at postsynaptic sites.

PMID- 17223278
TI  - Calorie restriction in nonhuman primates: assessing effects on brain and
      behavioral aging.
AB  - Dietary caloric restriction (CR) is the only intervention repeatedly demonstrated
      to retard the onset and incidence of age-related diseases, maintain function, and
      extend both lifespan and health span in mammals, including brain and behavioral
      function. In 70 years of study, such beneficial effects have been demonstrated in
      rodents and lower animals. Recent results emerging from ongoing studies of CR in
      humans and nonhuman primates suggest that many of the same anti-disease and anti
      aging benefits observed in rodent studies may be applicable to long-lived
      species. Results of studies in rhesus monkeys indicate that CR animals (30% less
      than controls) are healthier than fully-fed counterparts based on reduced
      incidence of various diseases, exhibit significantly better indices of
      predisposition to disease and may be aging at a slower rate based on analysis of
      selected indices of aging. The current review discusses approaches taken in
      studies of rhesus monkeys to analyze age-related changes in brain and behavioral
      function and the impact of CR on these changes. Approaches include analyses of
      gross and fine locomotor performance as well as brain imaging. In a related study
      it was observed that short-term CR (6 months) in adult rhesus monkeys can provide
      protection against a neurotoxic insult. Increasing interest in the CR paradigm
      will expand its role in demonstrating how nutrition can modulate the rate of
      aging and the mechanisms responsible for this modulation.

PMID- 17223279
TI  - Brief family treatment intervention to promote aftercare among male substance
      abusing patients in inpatient detoxification: A quasi-experimental pilot study.
AB  - We developed a brief family treatment (BFT) intervention for substance abusing
      patients in inpatient detoxification to promote aftercare treatment post-detox.
      BFT consisted of meeting with the patient and a family member (spouse or parent)
      with whom the patient lived to review and recommend potential aftercare plans for
      the patient. A phone conference was used when logistics prevented an in-person
      family meeting. Results indicated that male substance abusing patients who
      received BFT (N=14), as compared with a matched treatment as usual (TAU)
      comparison group (N=14) that did not, showed a trend toward being more likely to
      enter an aftercare program and to attend more days of aftercare in the 3 months
      after detoxification. The magnitude of these differences favoring BFT over TAU
      was midway between a medium and a large effect size. Days using alcohol or drugs
      in the 3 months after detox were lower for treatment-exposed BFT patients who had
      an in-person family meeting than TAU counterparts (trend, medium effect), and for
      patients who entered aftercare regardless of treatment condition (significant
      large effect).

PMID- 17223281
TI  - Prototype perception and smoking: are negative or positive social images more
      important in adolescence?
AB  - It is suggested that a more profound understanding of cigarette smoking among
      adolescents should include the social images they have of smokers. The main goal
      of the present study was to investigate the role of smoker prototypes in
      adolescents' smoking status and to compare the role of negative and positive
      smoker images. Data were collected from high school students in two counties of
      the Southern Plain Region of Hungary (N=548; ages between 14 and 21 years). The
      self-administered questionnaires contained items on sociodemographics, smoking
      occurrence, and smoker prototypes. Factor analysis revealed three smoker
      prototypes: a negative prototype (e.g., dull, childish), a positive social
      appearance prototype (e.g., cool, popular), and a positive individual competence
      prototype (such as smart, independent) all with satisfactory reliability. Odds
      ratios suggest that the role of the negative prototypes for nonsmokers is greater
      than the role of positive prototypes for smokers. For boys, positive individual
      competence prototype also seems to be important. Health promotion programs should
      focus on fostering negative social images in prevention.

PMID- 17223280
TI  - Thai War on Drugs: measuring changes in methamphetamine and other substance use
      by school students through matched cross sectional surveys.
AB  - In 2003 the Thai government announced a radical shift in drug policy with the
      implementation of a War on Drugs. Although consequences of this controversial
      measure (e.g. drug dealer deaths) have received widespread attention relatively
      little work has evaluated changes in substance use. We used two anonymous
      representative samples of secondary school students to compare drug use in
      Northeast Thailand before (1998; n=4217) and after (2004/5; n=3489) the War on
      Drugs. Results indicate that reported levels of current illicit drug use reduced
      significantly between 1998 and 2004/5 (for methamphetamine from 4.2% to 0.9%). By
      examining trends in year of first methamphetamine use we identify that observed
      reductions in drug initiation are temporally consistent with the War on Drugs.
      However, while prevalence of alcohol use has also fallen, there was a three-fold
      increase in daily alcohol use. We suggest that this rise, combined with other
      negative impacts of 'wars' on drugs, means drug control requires a public health
      perspective that sees eliminating drug use as part of a wider strategy that has
      improvement in population health, not just drug prevention, as its core
      objective.

PMID- 17223282
TI  - Reconstruction of ancestral nucleotide sequences and estimation of substitution
      frequencies in a star phylogeny.
AB  - Maximum likelihood phylogeny reconstruction methods are widely used in uncovering
      and assessing the evolutionary history and relationships of natural systems.
      However, several simplifying assumptions commonly made in this analysis limit the
      explanatory power of the results obtained. We present an algorithm that performs
      the phylogenetic analysis without making the common assumptions for sequence data
      from at least three leaf nodes in a star phylogeny. In particular, the underlying
      nucleotide substitution model does not have to be reversible and may include
      neighbor-dependent processes like the CpG methylation deamination process (CpG
      effect). The base composition of the sequences at the external nodes and the one
      of the ancestral sequence may be different from each other and they do not have
      to be stationary state distributions of the corresponding substitution model. The
      algorithm is able to reconstruct the ancestral base composition and accurately
      estimate substitution frequencies in the branches of the star phylogeny.
      Extensive tests on simulated data validate the very favorable performance of the
      algorithm. As an application we present the analysis of aligned genomic sequences
      from human, mouse, and dog. Different substitution pattern can be observed in the
      three lineages.

PMID- 17223283
TI  - Identification and characterization of matrix metalloproteinase-20 (MMP20;
      enamelysin) genes in reptile and amphibian.
AB  - Matrix metalloproteinase-20 (MMP20; enamelysin) is important for proteolytic
      processing of extracellular matrix (ECM) proteins during the formation of enamel
      and plays a critical role in proteolytic processing of amelogenin (AMEL), the
      most abundant enamel ECM protein. MMP20 might have played a role in the emergence
      of teeth, because jawless vertebrates with primordial teeth on their external
      skeletons may have possessed the MMP20 gene, and MMP20 and enamel ECM proteins
      are thought to have evolved together in a special relationship over time. Thus,
      an understanding of the molecular evolution of the MMP20 gene is important for
      elucidating the evolution of enamel and it is necessary to identify the orthologs
      of the MMP20 gene in non-mammals, as it has been identified in mammals. In the
      present study, orthologs of the MMP20 genes from a reptile (caiman) and an
      amphibian (African clawed toad) were cloned and characterized. Comparisons of the
      orthologs revealed that the MMP20 proteins were highly conserved throughout the
      evolution of tetrapods. Further, the caiman, toad, and mammalian MMP20 shared
      several unique features specific for MMP20, but not for other matrix
      metalloproteinases. In addition, the toad MMP20 gene was transcribed only in the
      upper jaw, presumably in teeth. These results suggest that MMP20 in a common
      ancestor of tetrapods might have been recruited for the processing of AMEL and
      conserved over 350 million years of evolution.

PMID- 17223284
TI  - Combinatorial epigenetics, "junk DNA", and the evolution of complex organisms.
AB  - At certain evolutionary junctures, two or more mutations participating in the
      build-up of a new complex function may be required to become available
      simultaneously in the same individuals. How could this happen in higher organisms
      whose populations are small compared to those of microbes, and in which chances
      of combined nearly simultaneous highly specific favorable mutations are
      correspondingly low? The question can in principle be answered for regulatory
      evolution, one of the basic processes of evolutionary change. A combined
      resetting of transcription rates in several genes could occur in the same
      individual. It is proposed that, in eukaryotes, changes in epigenetic trends and
      epigenetically transforming encounters between alternative chromatin structures
      could arise frequently enough so as to render probable particular conjunctions of
      changed transcription rates. Such conjunctions could involve mutational changes
      with low specificity requirements in gene-associated regions of non-protein
      coding sequences. The effects of such mutations, notably when they determine the
      use of histone variants and covalent modifications of histones, can be among
      those that migrate along chromatin. Changes in chromatin structure are often
      cellularly inheritable over at least a limited number of generations of cells,
      and of individuals when the germ line is involved. SINEs and LINEs, which have
      been considered "junk DNA", are among the repeat sequences that would appear
      liable to have teleregulatory effects on the function of a nearby promoter,
      through changes in their numbers and distribution. There may also be present
      preexisting unstably inheritable epigenetic trends leading to cellular
      variegation, trends endemic in a cell population based on DNA sequences
      previously established in the neighborhood. Either way, epigenetically
      conditioned teleregulatory trends may display only limited penetrance. The
      imposition at a distance of new chromatin structures with regulatory impact can
      occur in cis as well as in trans, and is examined as intrachromosomally spreading
      teleregulation and interchromosomal "gene kissing". The chances for two or more
      particular epigenetically determined regulatory trends to occur together in a
      cell are increased thanks to the proposed low specificity requirements for most
      of the pertinent sequence changes in intergenic and intronic DNA or in the
      distribution of middle repetitive sequences that have teleregulatory impact.
      Inheritable epigenetic changes ("epimutations") with effects at a distance would
      then perdure over the number of generations required for "assimilation" of the
      several regulatory novelties through the occurrence and selection, gene by gene,
      of specific classical mutations. These mutations would have effects similar to
      the epigenetic effects, yet would provide stability and penetrance. The described
      epigenetic/genetic partnership may well at times have opened the way toward
      certain complex new functions. Thus, the presence of "junk DNA", through co
      determining the (higher or lower) order and the variants of chromatin structure
      with regulatory effects at a distance, might make an important contribution to
      the evolution of complex organisms.

PMID- 17223285
TI  - Yersiniosis in zoo marmosets (Callitrix jacchuss) caused by Yersinia
      enterocolitica 4/O:3.
AB  - The aim of this research was to describe two fatal cases of Yersinia
      enterocolitica bioserotype 4/O:3 infection in non-human primates and to
      characterise the isolates by PCR and PFGE. In July 2004, two marmosets (Callitrix
      jacchuss) born in captivity in Zagreb Zoo, died following a few days of
      intermittent diarrhoea in intervals of 2 weeks. The pathomorphological diagnosis
      of the female (born in 1997) and the male (born in 1995) marmoset, was
      disseminated miliary necrosis of the liver. Y. enterocolitica 4/O:3 was isolated
      from both livers showing that monkeys are susceptible to this bioserotype. The
      ail gene, which is an essential chromosomal virulence factor in pathogenic Y.
      enterocolitica isolates, was present in the marmoset isolates. Two different PFGE
      patterns were obtained from the isolates of the male liver with NotI enzyme. One
      genotype of the male marmoset isolate was indistinguishable from the genotype of
      the female marmoset isolate when NotI, ApaI and XhoI enzymes were used indicating
      a common infection source for the marmosets. The genotypes of the marmoset
      isolates differed only slightly from one human (of seven Croatian isolates) and
      from one pig isolate (representing a common genotype found among human and
      porcine isolates in Germany) suggesting that raw pork fed to the marmoset could
      have been the infection source.

PMID- 17223286
TI  - Multiplex PCR assay for the detection of high virulence rabbit Staphylococcus
      aureus strains.
AB  - High virulence rabbit Staphylococcus aureus strains, which are clonal in origin,
      are responsible for the spread of chronic staphylococcosis at the rabbit flock
      level. The aim of the present study was to develop a multiplex PCR assay that can
      be used for the identification of these high virulence strains. Two targets of
      the assay were the bbp and the selm genes, which have recently been shown to
      occur specifically in high virulence isolates. A third target was a sequence
      designated "flank", which was derived from a previously generated high virulence
      specific RAPD pattern. Furthermore, the femA gene, which is specific for S.
      aureus, was incorporated in order to avoid false negative results due to
      insufficient DNA preparation. The multiplex PCR was successful at differentiating
      the 26 typical high virulence and 50 low virulence rabbit S. aureus strains
      incorporated in the present study. Therefore it is useful for the initial
      screening of newly acquired breeding stock, in order to prevent the intake of
      high virulence strains in rabbitries.

PMID- 17223287
TI  - Prevalence of Helicobacter equorum in faecal samples from horses and humans.
AB  - Recently, a new enterohepatic Helicobacter species, H. equorum, was isolated from
      faecal samples of two clinically healthy horses. At the onset of this study,
      nothing was known about the prevalence of this organism in horses, nor was there
      any information available on the possible zoonotic character of this agent. This
      study aimed to determine the prevalence of H. equorum in faecal samples from
      equine and human origin. Therefore, faecal samples of 120 healthy privately owned
      horses, 227 healthy riding-school horses and 239 hospitalised horses were
      screened for H. equorum-DNA by means of a PCR amplifying a 1074-bp fragment of
      the 23S rRNA gene with primers specific for H. equorum. The vast majority of the
      hospitalised horses were under treatment with an antimicrobial agent at the
      moment of sampling, while the other horses had not been treated with an
      antimicrobial agent in the 14 days preceding the sampling. Stool samples of 531
      humans suffering from gastro-intestinal disease and 100 clinically healthy humans
      were likewise examined. H. equorum-DNA was demonstrated in faeces from 0.8% of
      the privately owned horses, 3.1% of the riding-school horses and 7.9% of the
      hospitalised horses. The prevalence of H. equorum was significantly higher in
      hospitalised than in healthy, privately owned horses (P=0.02). H. equorum-DNA was
      not detected in human samples. These results indicate that the prevalence of H.
      equorum in horses may be influenced by the health status of the investigated
      horse population and/or by antimicrobial treatment. We may additionally assume
      that this micro-organism does not commonly infect humans.

PMID- 17223288
TI  - Progesterone receptors, oestrogen receptor alpha and glucocorticoid receptors in
      the bovine intercaruncular uterine wall around parturition.
AB  - The bovine intercaruncular uterine wall expresses steroid hormone receptors
      throughout pregnancy. Concentrations of specific hormones undergo massive changes
      during the peripartal period and modulate the synthesis of their own receptors.
      This is well documented for the placentome, but respective data concerning the
      intercaruncular uterine wall are completely lacking. Thus, intercaruncular
      uterine wall segments from cows (I) being 8 and 9 months pregnant (slaughtered
      cows) and (II) cows undergoing a premature caesarean section 269-282 days after
      artificial insemination (AI) with (IIa, b) or without (IIc) induction of birth
      with PGF(2alpha) agonist or (III) receiving a caesarean section during severe
      dystocia (n=6, 5, 5, 5, 6 and 4 animals, respectively) were studied. In four
      naturally calving cows (IV) endometrial biopsies were obtained within 30 min
      after the expulsion of the calf. All tissue probes were fixed for 24h in 4%
      formaldehyde, routinely embedded in paraffin, and cut at 4 microm. Progesterone
      receptors (PR), estrogen receptor alpha (ERalpha) and glucocorticoid receptors
      (GR) were assessed using specific antibodies and staining intensities were
      documented employing an immunoreactive score (IRS). PR, ERalpha and GR exhibited
      cell type- and location-specific distribution patterns. IRS for PR and ERalpha
      did not differ between groups. GR-IRS of endometrial stromal cells, however, were
      higher in animals undergoing premature caesarean section after induction of birth
      compared to animals slaughtered during month 8 or 9 of pregnancy or animals
      receiving caesarean section following dystocia. Results of the present study
      indicate that steroid hormone receptor amounts within the intercaruncular uterine
      wall do not (PR, ERalpha) - or in a tissue-specific manner (GR) only - change
      during the peripartal period, although respective hormones undergo massive
      changes during this period. This is in strict contrast to the placentome.
      Comparatively lower local tissue estrogen concentrations around term may be one
      cause for this difference.

PMID- 17223289
TI  - Effect of n-scCO(2) on crystalline to amorphous conversion of carbamazepine.
AB  - A number of studies have been carried out to investigate the crystalline to
      amorphous conversion of carbamazepine (CBZ) using solid dispersion techniques. In
      this study we have tried to achieve conversion using a novel technique combining
      near-supercritical carbon dioxide (n-scCO(2)) and pharmaceutically acceptable
      polymers (Na CMC and PVP) of varying molecular weights. Physical mixtures were
      prepared in two identical sets, one exposed to n-scCO(2) treatment and other was
      untreated. The treated physical mixtures were compared to untreated using PXRD,
      DSC and USP in vitro dissolution techniques. Routinely used PXRD analysis
      involves qualitative estimation of the amorphous conversion of a drug. In this
      work a previously developed mathematical parameter, ratio of ratios (ROR), was
      utilized to better quantify the crystalline to amorphous conversion of CBZ. The
      findings from the three methods indicated that only the lowest molecular weight
      PVP, PVP10k, facilitated significant crystalline to amorphous conversion of CBZ.
      In vitro dissolution, which is considered as an estimate of bioavailability
      demonstrated an initial dissolution of CBZ significantly greater in the treated
      physical mixtures of PVP10k:CBZ than the initial dissolution of the corresponding
      untreated physical mixtures and pure untreated CBZ.

PMID- 17223290
TI  - Preparation of dual crosslinked alginate-chitosan blend gel beads and in vitro
      controlled release in oral site-specific drug delivery system.
AB  - Alginate-chitosan (ALG-CS) blend gel beads were prepared based on Ca2+ or dual
      crosslinking with various proportions of alginate and chitosan. The homogeneous
      solution of alginate and chitosan was dripped into the solution of calcium
      chloride; the resultant Ca2+ single crosslinked beads were dipped in the solution
      of sodium sulfate sequentially to prepare dual crosslinked beads. The dual
      crosslinkage effectively promoted the stability of beads under gastrointestinal
      tract conditions. The sustained release profiles of single and dual crosslinked
      gel beads loaded bovine serum albumin (BSA), a model protein drug, were
      investigated in simulated gastric fluid (SGF), simulated intestinal fluid (SIF)
      and simulated colonic fluid (SCF). In SGF, compared to Ca2+ single crosslinked
      beads, from which BSA released fast and the cumulative drug release percentages
      were about 80% of all formations in 4 h, the BSA total release from dual
      crosslinked gel beads was no more than 3% in 8 h. In SIF and SCF, Ca2+ single
      crosslinked beads were disrupted soon associating with the fast drug release. As
      to the dual crosslinked beads, the BSA total release from the ALG-CS mass ratio
      9:1 (81.24%) was higher than that of 7:3 and 5:5 (less than 60%) in 8 h in SIF;
      the BSA release from all beads was much faster in SCF than in SIF. The dual
      crosslinked beads incubated in gastrointestinal tract conditions, the BSA
      cumulative release of ALG-CS mass ratios 9:1, 7:3 and 5:5 were respectively 2.35,
      1.96, 1.76% (in SGF 4 h), 82.86, 78.83, 52.91% (in SIF 3 h) and 97.84, 96.81,
      87.26% (in SCF 3 h), which suggested that the dual crosslinked beads have
      potential small intestine or colon site-specific drug delivery property.

PMID- 17223291
TI  - Design of novel antifungal mucoadhesive films. Part II. Formulation and in vitro
      biopharmaceutical evaluation.
AB  - This paper deals with the formulation of the mucoadhesive films containing
      nystatin. The design and formulation of the films were based on the mucoadhesive
      properties of carbomer 934P (CB) and carboxymethycellulose (NaCMC), and also on
      the plasticizer properties of polyethyleneglycol 400 (PEG400). A surfactant
      (ascorbyl palmitate, ASC16) was added to the system to aid in nystatin
      dispersion. Addition of these last two components produced a significant
      improvement in physical-mechanical properties (flexibility and strength) as well
      as an increase in the nystatin release rate. X-ray powder diffraction (XRPD) and
      scanning electronic microscopy (SEM) were used to evaluate the morphological
      changes in the films while PEG400 and ASC16 were added to the formulations.
      Furthermore, the in vitro nystatin profile release was determined.

PMID- 17223292
TI  - Ftorafur loading and controlled release from poly(ethyl-2-cyanoacrylate) and
      poly(butylcyanoacrylate) nanospheres.
AB  - In the present work, a method is described to prepare polymeric colloidal
      nanospheres, consisting of poly(ethyl-2-cyanoacrylate) (PE-2-CA) or
      poly(butylcyanoacrylate) (PBCA), loaded with the anticancer drug ftorafur. The
      method is based on the anionic polymerization procedure, often used in the
      synthesis of poly(alkylcyanoacrylate) nanospheres for drug delivery. A detailed
      investigation of the capabilities of both polymeric nanoparticles to load this
      drug is shown. The effect of synthesis residuals and degradation products on the
      absorbance of supernatants was considered in the loading and release measurement
      methodologies, because of their potential perturbing influence on the
      determination of ftorafur concentration in solution. We found the existence of
      two mechanisms of drug incorporation: absorption or entrapment in the polymeric
      network, and surface adsorption, detectable by means of zeta potential and
      spectrophotometric measurements. Among the factors affecting the drug
      incorporation to the polymer network, the type of polymer, the pH and the drug
      concentration are the main determining ones. Moreover, the acidity of the medium
      needs to be controlled in order to avoid the formation of macroaggregates of
      solids. The optimum loading conditions were used to perform ftorafur release
      evaluations from polymeric particles, and the influence of the mechanism of drug
      incorporation, the amount of drug loaded, and the type of polymer on the drug
      release were studied.

PMID- 17223293
TI  - Formulation and cytotoxicity of doxorubicin loaded in self-assembled bio
      polyelectrolyte microshells.
AB  - A bio-polyelectrolyte microshell composed of alginate sodium (ALG) and chitosan
      (CHI) was fabricated by electrostatic layer-by-layer (LbL) self-assembly
      technique. The resulting ALG-CHI microshells were found to be able to effectively
      load anti-cancer drug doxorubicin (DOX) in the interior of the shells under
      modest conditions without addition of other reagents, as demonstrated by confocal
      laser scanning microscopy (CLSM). The mass of DOX loaded in one capsule of four
      alginate/chitosan layers (i.e. the volume V=2.5x10(-10) cm3) is calculated as ca.
      1.4x10(-13) g, which corresponds to 1.5x10(8) DOX molecules. Also, the release of
      DOX in the shells is dependent on the number of assembled layers of the shells.
      Colorimetric XTT cell viability assay results showed that the DOX-loaded
      microshells at high concentrations tested could kill cancer cells more
      efficiently than free-DOX alone.

PMID- 17223294
TI  - Construction of nanoscale multicompartment liposomes for combinatory drug
      delivery.
AB  - Liposomes are clinically used delivery systems for chemotherapeutic agents,
      biological macromolecules and diagnostics. Due to their flexibility in size and
      composition, different types of liposomes have been developed varying in surface
      and structural characteristics. Multicompartment liposomes constitute an
      attractive drug carrier system offering advantages in terms of inner vesicle
      protection, sustained drug release and possibility for combinatory (cocktail)
      therapies using a single delivery system. However, all previously described
      methodologies for multicompartment or multivesicular liposomes resulted in
      micrometer-sized vesicles limiting most pharmaceutical applications. In this work
      we report formulation of nanoscale multicompartment liposomes which maybe
      applicable for systemic administration. A small unilamellar vesicle (SUV) aqueous
      dispersion (DOPC:DOPG:CHOL) was used to hydrate a dried film of different lipid
      contents (DMPC:CHOL), followed by extrusion. The system was characterised by
      techniques such as photon correlation spectroscopy (PCS), zeta potential
      measurement, transmission electron microscopy (TEM) and laser scanning confocal
      microscopy (LSCM). We observed a single, multicompartment vesicle population
      composed of the two different bilayer types of approximately 200 nm in mean
      diameter rather than a mixture of two independent vesicle populations. In the
      case of tumour therapy, such multicompartment liposome systems can offer a single
      carrier for the delivery of two different modalities.

PMID- 17223295
TI  - Development and evaluation of a novel dry-coated tablet technology for pellets as
      a substitute for the conventional encapsulation technology.
AB  - Pellet formulations as represented by multiparticulate systems are often
      contained in hard capsules. We examined the use of a different approach to the
      making of compressed tablets containing pellets, OSDRC-technology. OSDRC
      technology employs a double-structure punch (center punch and outer punch)
      allowing for dry-coated tablets to be assembled in a single run. We examined the
      effects of the thickness of the outer punch, formability of pellets, and diameter
      of tablets on pellet filling. The results revealed that thinner outer punches are
      not always better for filling small tablets with large amounts of pellets. We
      considered that this was because the core pellets spread in a cone shape within
      the formulating tablets at filling, requiring a thickness of the outer punch and
      a particle density of the diluents at which pellets would not exude from the
      formulating tablets. It was suggested that the formability of core pellets
      affects the maximum number of layers of pellets, and higher formability would
      yield better results. However, we found that pellets with poor formability
      (tensile strength of < or =2 kPa) could be used in tablets. For the tablets, the
      larger the diameter, the greater the maximum number of layers. We considered this
      to be due to the friction between the pellets and punch wall. We concluded that
      OSDRC-technology could be applied to capsule-like forms containing pellets > or
      =50 wt% through an unconventional approach.

PMID- 17223296
TI  - Temporal integration in the gerbil: the effects of age, hearing loss and
      temporally unmodulated and modulated speech-like masker noises.
AB  - We characterized temporal integration for 2k Hz pure tones with durations between
      10 and 1000 ms in young, normal hearing old and old gerbils with a small hearing
      loss. Thresholds determined in silence increased for durations below 300 ms and
      were on average more than 10 dB higher for the 10 ms signal than asymptotic
      thresholds for the long signals. The amount of temporal integration tended to be
      less in gerbils with hearing loss. Threshold determination was repeated in the
      same individuals in the presence of speech-like unmodulated and modulated masking
      noises. Threshold shift due to the maskers was inversely related to the threshold
      in silence resulting in a reduced inter-individual variability of thresholds in
      both masking conditions. Thresholds differed systematically between both masker
      types in a duration dependent fashion. For long signal durations (300 and 1000
      ms) thresholds were on average 2dB lower and for the 10 ms signal 1.9 dB higher
      in the presence of the modulated masker. These differences in threshold obtained
      with the two maskers were significant. One hypothesis is that long signals can be
      detected in the troughs of the modulated masker, while peaks interfere with the
      detection of short signals.

PMID- 17223297
TI  - The effects of lateralized adaptors on lateral position judgements of tones
      within and across frequency channels.
AB  - Two experiments examined the effect of highly lateralized adaptor tone pulses on
      the perceived intracranial location of subsequent test tones. In Experiment 1,
      adaptor tones of each of two frequencies, highly lateralized to opposite sides by
      a quarter-period interaural time difference (ITD), were found to shift the
      perceived intracranial location of test tones of each adaptor frequency away from
      the side of the adaptor. The shift in perceived location was seen for all test
      tone ITDs with the same sign as the adaptor tone, and sometimes extended to
      include test tones with small ITDs favoring the opposite ear. The generality of
      the effect across test tone ITDs of the same sign as the adaptor suggests that
      the human auditory lateralization system is built of two (left, right) hemifield
      tuned azimuthal channels, and that perceived lateral location depends on the
      relative outputs of those two channels. In Experiment 2, the perceived location
      of test tones lateralized by ITD was studied in the same listeners at each of the
      same two frequencies, but after selective adaptation with tone pulses of only one
      frequency and laterality. The perceived lateral position of test tones with the
      same frequency as that of the adaptor underwent the same changes as seen in
      Experiment 1. The perceived lateral position of test tones of the nonadapted
      frequency usually shifted weakly in the opposite direction, i.e., in the
      direction expected if the second adaptor from Experiment 1 had actually been
      present. These data have implications both for the processes mediating selective
      adaptation using contingent stimuli, and for the azimuthal tuning of auditory
      spatial channels in man.

PMID- 17223298
TI  - Improving abnormal hemorheological parameters in aging guinea pigs by water
      soluble extracts of Salvia miltiorrhiza Bunge.
AB  - Salvia miltiorrhiza Bunge, known as Danshen in Chinese traditional medicine is
      effective at promoting blood circulation and removing (or decreasing) blood
      stasis. In the present study, we selected aging, 24-month-old guinea pigs as the
      animal experimental models and fed them a diet containing 75, 100 or 150 mg/(kg
      day) of water-soluble extract components of Salvia miltiorrhiza Bunge (WSm) for
      28 days, respectively, in order to evaluate the effects of WSm on their abnormal
      hemorheological parameters. The results showed that the blood biochemical
      parameters of the aging guinea pigs remained unaffected by orally given WSm
      compared to the controls, except that the fibrinogen levels of the group fed the
      high dose of WSm (150 mg/(kg day)) decreased. Aging guinea pigs fed a low dose of
      WSm (75 mg/(kg day)) showed no significant difference in hemorheological
      parameters. However, feeding of WSm at 100 mg/(kg day) (medium dose),
      significantly reduced erythrocyte membrane MDA levels, which probably increased
      erythrocyte deformability and decreased erythrocyte flow resistance, though no
      improvement in erythrocyte aggregation, blood viscosity, and blood
      viscoelasticity could be observed. Furthermore, when the dose reached 150 mg/(kg
      day) of WSm (high dose), a significant decrease in whole blood viscosity was
      observed at high, medium and low shear rates. Blood viscosity and viscoelasticity
      exhibited significant improvement in oscillatory measurements. Also, we found
      that the oxygen transport efficiency of whole blood increased.

PMID- 17223299
TI  - Evaluation of the antinociceptive effect of Rosmarinus officinalis L. using three
      different experimental models in rodents.
AB  - The rationale of this investigation was to examine the antinociceptive effect of
      an ethanol extract of Rosmarinus officinalis (RO) aerial parts, using three
      different experimental models: acetic acid-induced writhing test and formalin
      test in mice; and a model of arthritic pain: "pain-induced functional impairment
      model in the rat (PIFIR model)". The antinociceptive efficacies were evaluated
      using several dose-response curves and time courses. The antinociceptive effects
      from RO extract were compared with the antinociceptive effect of either tramadol
      (TR: 3.16-50 mg/kg, i.p. in mice, and 1.0-31.62 mg/kg, i.p. in rats) or
      acetylsalicylic acid (AA: 31.62-562.32 mg/kg, p.o.). RO extract (10-300 mg/kg,
      p.o.) significantly (P < 0.001) reduced the number of writhing movement induced
      by the i.p. administration of acetic acid solution in a dose-dependent way (ED50
      = 108.84 mg/kg, whereas, TR showed an ED50 = 12.38 mg/kg). In addition, RO
      extract (30-300 mg/kg) significantly (P < 0.001) inhibited licking and shaking
      behaviours in both early (neurogenic pain) and in the late (inflammatory pain)
      phases of the formalin test. These effects were like those produced by TR.
      Concerning the results using the PIFIR model, RO extract (30-3000 mg/kg, p.o.)
      like either TR or AA, produced a significant (P < 0.001) and dose-dependent
      antinociceptive response in rats (RO: ED50 = 222.78 mg/kg versus TR: ED50 = 11.06
      mg/kg and AA: ED50 = 206.13 mg/kg). These results strongly suggest that aerial
      parts of RO possess antinociceptive and anti-inflammatory activity, and reinforce
      the use of this plant in folk medicine.

PMID- 17223300
TI  - Syntrophomonas wolfei subsp. methylbutyratica subsp. nov., and assignment of
      Syntrophomonas wolfei subsp. saponavida to Syntrophomonas saponavida sp. nov.
      comb. nov.
AB  - A spore-forming bacterium strain 4J5(T) was isolated from rice field mud. When co
      cultured with Methanobacterium formicicum DSM 1535(T), strain 4J5(T) could
      syntrophically degrade saturated fatty acids with 4-8 carbon atoms, including 2
      methylbutyrate. Phylogenetic analysis based on 16S rRNA gene similarity showed
      that strain 4J5(T) was most closely related to Syntrophomonas wolfei subsp.
      wolfei DSM 2245(T) (98.9% sequence similarity); however, it differed from the
      latter in the substrates utilized and its genetic characteristics. Therefore, a
      new subspecies Syntrophomonas wolfei subsp. methylbutyratica is proposed. The
      type strain is 4J5(T) (=CGMCC 1.5051(T)=JCM 14075(T)). Furthermore, based on 16S
      rRNA sequence divergence and substrate utilization, we propose the assignment of
      Syntrophomonas wolfei subsp. saponavida DSM 4212(T) to Syntrophomonas saponavida
      sp. nov. comb. nov.

PMID- 17223301
TI  - A validated stability indicating LC method for oxcarbazepine.
AB  - The present paper describes the development of a stability indicating reversed
      phase liquid chromatographic (RPLC) method for oxcarbazepine in the presence of
      its impurities and degradation products generated from forced decomposition
      studies. The drug substance was subjected to stress conditions of hydrolysis,
      oxidation, photolysis and thermal degradation. The degradation of oxcarbazepine
      was observed under base hydrolysis. The drug was found to be stable to other
      stress conditions attempted. Successful separation of the drug from the synthetic
      impurities and degradation product formed under stress conditions was achieved on
      a C18 column using mixture of aqueous 0.02 M potassium dihydrogen phosphate
      acetonitrile-methanol (45:35:20, v/v/v) as mobile phase. The developed HPLC
      method was validated with respect to linearity, accuracy, precision, specificity
      and robustness. The developed HPLC method to determine the related substances and
      assay determination of oxcarbazepine can be used to evaluate the quality of
      regular production samples. It can be also used to test the stability samples of
      oxcarbazepine.

PMID- 17223303
TI  - Clinical utility of time-resolved imaging of contrast kinetics (TRICKS) magnetic
      resonance angiography for infrageniculate arterial occlusive disease.
AB  - OBJECTIVE: The diagnostic accuracy of magnetic resonance angiography (MRA) in the
      infrapopliteal arterial segment is not well defined. This study evaluated the
      clinical utility and diagnostic accuracy of time-resolved imaging of contrast
      kinetics (TRICKS) MRA compared with digital subtraction contrast angiography
      (DSA) in planning for percutaneous interventions of popliteal and infrapopliteal
      arterial occlusive disease. METHODS: Patients who underwent percutaneous lower
      extremity interventions for popliteal or tibial occlusive disease were identified
      for this study. Preprocedural TRICKS MRA was performed with 1.5 Tesla (GE
      Healthcare, Waukesha, Wis) magnetic resonance imaging scanners with a flexible
      peripheral vascular coil, using the TRICKS technique with gadodiamide injection.
      DSA was performed using standard techniques in angiography suite with a 15-inch
      image intensifier. DSA was considered the gold standard. The MRA and DSA were
      then evaluated in a blinded fashion by a radiologist and a vascular surgeon. The
      popliteal artery and tibioperoneal trunk were evaluated separately, and the
      tibial arteries were divided into proximal, mid, and distal segments. Each
      segment was interpreted as normal (0% to 49% stenosis), stenotic (50% to 99%
      stenosis), or occluded (100%). Lesion morphology was classified according to the
      TransAtlantic Inter-Society Consensus (TASC). We calculated concordance between
      the imaging studies and the sensitivity and specificity of MRA. The clinical
      utility of MRA was also assessed in terms of identifying arterial access site as
      well as predicting technical success of the percutaneous treatment. RESULTS:
      Comparisons were done on 150 arterial segments in 30 limbs of 27 patients. When
      evaluated by TASC classification, TRICKS MRA correlated with DSA in 83% of the
      popliteal and in 88% of the infrapopliteal segments. MRA correctly identified
      significant disease of the popliteal artery with a sensitivity of 94% and a
      specificity of 92%, and of the tibial arteries with a sensitivity of 100% and
      specificity of 84%. When used to evaluate for stenosis vs occlusion, MRA
      interpretation agreed with DSA 90% of the time. Disagreement occurred in 15
      arterial segments, most commonly in distal tibioperoneal arteries. MRA
      misdiagnosed occlusion for stenosis in 11 of 15 segments, and stenosis for
      occlusion in four of 15 segments. Arterial access was accurately planned based on
      preprocedural MRA findings in 29 of 30 patients. MRA predicted technical success
      83% of the time. Five technical failures were due to inability to cross arterial
      occlusions, all accurately identified by MRA. CONCLUSION: TRICKS MRA is an
      accurate method of evaluating patients for popliteal and infrapopliteal arterial
      occlusive disease and can be used for planning percutaneous interventions.

PMID- 17223304
TI  - Quality of life outcomes following laparoscopic total mesorectal excision for low
      rectal cancers: a clinical control study.
AB  - AIMS: To evaluate the health-related quality of life (HRQoL) outcomes in patients
      undergoing laparoscopic total mesorectal excision (LTME) with anal sphincter
      preservation (ASP) for low rectal cancers. METHODS: Patients undergoing LTME with
      ASP or open procedures (OTME) for low rectal cancers were prospectively followed
      up. All patients were treated in curative attempt and were free of local
      recurrence during the study. HRQoL was assessed by questionnaires during 3-6
      months, 12-18 months, and 2-5 years after surgery. RESULTS: From June 2001 to
      March 2006, 125 patients undergoing LTME and 103 undergoing OTME were included in
      this study. In contrast to OTME patients, the LTME ones showed significantly
      better physical function during 3-6 months after surgery, less micturition
      problems within 12-18 months, less male sexual problems and better sexual
      function during 12-18 months after surgery, with better sexual enjoyment after 24
      months postoperatively. Both groups showed significant improvement in most
      subscales from the first to the second assessment, and an improvement in sexual
      enjoyment from the second to the third assessment. The sexual function,
      micturition problems and male sexual problems in the LTME group significantly
      improved from the first to the second assessment, whereas the sexual function in
      the OTME group improved from the second to the third assessment. CONCLUSIONS:
      Patients undergoing LTME for low rectal cancers can achieve superior
      postoperative HRQoL than patients undergoing OTME, with superior physical
      function, micturition function, overall sexual and male sexual functions in the
      short term, and better sexual enjoyment in the long term. The HRQoL of both LTME
      and OTME patients may be expected to improve over time, particularly over the
      first postoperative year.

PMID- 17223305
TI  - Role of frozen section associated with intraoperative cytology in comparison to
      FNA and FS alone in the management of thyroid nodules.
AB  - AIMS: The utilization of fine needle aspiration (FNA) biopsy is an accurate and
      cost-effective method in the diagnosis of thyroid diseases. However, the non
      diagnostic cases and cases of suspicious carcinoma remain a dilemma, and in these
      cases thyroidectomy is usually recommended, even if only 15-20% of these patients
      really need a thyroidectomy. To avoid unnecessary surgical treatment, frozen
      section (FS) is usually performed. This method is well recognized, but is not
      useful for the diagnosis of follicular lesions. Therefore, many authors have
      tried to increase the specificity and sensibility of intraoperative examination,
      supporting it with an intraoperative cytological technique (IC). To clarify the
      role of intraoperative exam (FS and IC), also comparing to FNA, we have reviewed
      our own experiences. METHODS: In a period covering 6 years (2000-2005), FS was
      performed in 1,472 cases out of 11,420 total thyroidectomy operations. FS
      diagnosis and definitive diagnosis, were reviewed and confirmed, moreover, FNA
      diagnosis and definitive diagnosis were also considered and all intraoperatory
      cytological slides were reviewed. Diagnostic accuracy was assessed for FNA and FS
      with or without intraoperative cytology. We compared 1,472 FS diagnoses with
      their definitive histological diagnosis; 728 FNA out of 1,472 patients with
      definitive histological diagnosis, and 564 FS associated with IC out of 1,472
      patients with definitive diagnosis. RESULTS: The diagnostic accuracy of these
      three methods were, respectively, 88.8%, 88.8% and 95.7%. CONCLUSION: We can
      assert that FS associated with IC remains the most accurate technique in the
      surgical management of thyroid nodules.

PMID- 17223306
TI  - [Evaluation of postoperative analgesia with continuous iliofascial nerve sheath
      block after total hip arthroplasty replacement: a pilot study].
AB  - OBJECTIVE: To assess the analgesic efficiency of a continuous iliofascial nerve
      sheath block after total hip arthroplasty replacement (RPTH). STUDY DESIGN: open
      and prospective pilot study. PATIENTS AND METHODS: Before induction of general
      anaesthesia (GA), an iliofascial catheter was inserted (group KT, n = 11) or not
      (group NKT, n = 10). In the KT group, 30 ml of ropivacaine 4,75 mg/ml (maximum
      dose) were injected, and 14 mg/h of ropivacaine 2 mg/ml were infused during the
      first 48 postoperative hours. All patients underwent a standardized GA and a
      multimodal postoperative analgesia with a intravenous PCA morphine, paracetamol
      and tramadol during the first 48 hours. Postoperative pain assessment which was
      achieved using visual analogic scores (VAS) at rest (EVAr) and on movement
      (EVAm), total morphine consumption, and side effects were collected during the
      first 48 hours. Statistical analysis was performed using a Mann and Whitney test
      for the quantitative values and a chi 2 exact test for the qualitative values.
      Data are expressed as median [interquartile range]. RESULTS: Total morphine
      consumption was lower in the KT group with a total amount of 26 mg [11-48] versus
      77.5 mg [55-91] (p = 0.007) at h48. EVAr and EVAm were lower in the KT group at
      h4, h8, h24, h36 for the EVAr and during the 48 postoperative hours for EVAm.
      Three patients experienced nausea and/or vomiting in the KT group versus 6 in the
      NKT group (p = 0.05). CONCLUSION: After RPTH surgery, continuous iliofascial
      block reduces morphine consumption; provide a better pain relief at rest and on
      movement than IV multimodal analgesia alone.

PMID- 17223307
TI  - The prevalence and risk of hepatitis flares in a Serbian cohort of HIV and HCV co
      infected patients treated with HAART.
AB  - Despite substantial benefits of HAART treatment of HIV-infected patients,
      cumulative long-term toxicity, including drug-induced hepatotoxicity, has emerged
      as an important complication. Thus, to examine the prevalence and risk of
      developing severe hepatic injury during HAART, we conducted a retrospective study
      in a cohort of 364 HIV-infected patients treated with HAART between January 1998
      and May 2006, for whom data on alanine aminotransferase activity were available
      both before and during HAART. HCV co-infection was recorded in 35.4% of the
      series, but was found not to influence either the efficacy of HAART or survival
      (P>0.05). Severe hepatotoxicity occurred in a total of 24 patients (6.6%).
      Multivariate logistic regression defined HCV co-infection (OR 16.6, 95% CI 3.8
      46.0, P<0.0001), and the use of SQV/RTV and d4T (OR 3.1, 95% CI 1.2-8.16, P=0.02,
      and OR 7.1, 95% CI 1.0-54.5, P=0.05, respectively) as independent risk factors
      for aggravation of hepatitis. In addition, there was a significant increase in
      the probability of developing liver damage over years of treatment (Log rank,
      P<0.01). Conversely, the probability of developing hepatotoxicity was not
      associated with an increase in the CD4 cell count to values greater than
      350/microL (Log rank, P=0.59). In conclusion, in the setting of chronic viral
      hepatitis, hepatotoxicity during HAART may be attributed to the cumulative
      toxicity of drugs that induce mitochondrial toxicity, along with particular PIs
      and/or NNRTIs. Furthermore, our data suggest prudent use of D-drugs, still common
      in resource-limited countries, in HCV co-infected patients.

PMID- 17223308
TI  - Real-time PCR assay for rapid detection and quantification of Campylobacter
      jejuni on chicken rinses from poultry processing plant.
AB  - Campylobacter jejuni (C. jejuni) is the leading cause of food-borne
      gastroenteritis in the United States. Detection of Campylobacter in food samples
      by conventional culture is cumbersome; therefore, there is a need to develop
      rapid and cost-effective detection and quantification methods. Eighty-four whole
      chicken rinses were collected at different stages of processing at three poultry
      processing plants. After chicken wash collection and DNA extraction, the samples
      were directly subjected to real-time PCR (rtPCR) without enrichment and also
      culture. The assay specificity was determined with a range of Campylobacter
      species, related, and unrelated organisms. Of the 84 samples collected 65 (77%)
      of the samples were positive by the rtPCR assay and 27 (32%) of the samples
      tested positive by direct plating to selective agar media. The results were
      positively concordant for 27 (32%) of the samples. The whole rtPCR assay can be
      completed within 90min with a detection limit of 1CFU, compared to 5-7 days for
      enrichment and sub culturing in selective agar. This assay is the first report of
      rtPCR method capable of detecting and quantifying C. jejuni from chicken rinses
      without an enrichment step and could be an important, rapid and quantification
      model for other food-borne pathogens.

PMID- 17223309
TI  - Mandibular symphyseal distraction osteogenesis: review of three techniques.
AB  - Mandibular symphyseal distraction osteogenesis (MSDO) is an alternative strategy
      to correct mandibular transverse deficiencies and dental crowding. Only a limited
      number of practitioners have reported their clinical experience and potential
      complications of this procedure to widen the mandible in a large case series.
      This study involved retrospective analysis of 40 patients who underwent
      mandibular symphyseal distraction osteogenesis. Three different types of
      distractor were used to widen the mandible: tooth-borne in 21 patients, bone
      borne in 5 patients and hybrid (both bone and tooth-borne) in 14 patients. The
      distraction amount ranged from 7 to 11 mm (mean 7.31 mm). While 39 patients
      underwent successful mandibular symphyseal distraction, there was one failure.
      Most of the complications were experienced in bone-borne distractors, such as
      breakage of the distractor rod, gingival recession, secondary infection and
      ptosis of the chin. In the light of these findings, it is suggested that a
      lingually placed tooth-borne hyrax appliance is more suitable and reliable than
      the other distraction devices. Further larger studies are needed in order to
      better evaluate the effectiveness of bone-borne or hybrid devices.

PMID- 17223310
TI  - Condylar injury: magnetic resonance imaging findings of temporomandibular joint
      soft-tissue changes.
AB  - Recent studies have suggested magnetic resonance imaging (MRI) as useful in the
      evaluation of soft-tissue changes that occur in the temporomandibular joint (TMJ)
      after acute condylar trauma. The aim of this study was to investigate whether MRI
      findings of disc displacement, capsular tear and haemarthrosis are linked to the
      degree of condylar injury. Nineteen patients were assigned a diagnosis of uni- or
      bilateral condylar fracture (n=17), or condylar contusion with a uni- or
      bilateral diagnosis of TMJ sprain/strain (n=2). Condylar injuries were classified
      as grade I (absence of condylar fracture), grade II (type I, II or III condylar
      fracture), and grade III (type IV, V or VI condylar fracture). Bilateral sagittal
      and coronal MR images were obtained immediately after injury to establish the
      presence or absence of disc displacement, haemarthrosis and capsular tear. The
      data revealed a significant relationship between the degree of condylar injury
      and the MRI findings of capsular tear (P=0.000) and haemarthrosis (P=0.000), and
      between the MRI diagnoses of capsular tear and haemarthrosis (P=0.000). There was
      good diagnostic agreement between the presence of grade III condylar injury and
      the MRI diagnoses of capsular tear (K=0.62) and haemarthrosis (K=0.60). The
      results suggest that degree of condylar injury is related to MRI findings of
      capsular tear and haemarthrosis, and that MRI to supplement diagnosis of grade
      III condylar injury is warranted.

PMID- 17223311
TI  - Alterations of p16INK4a tumour suppressor gene in mucoepidermoid carcinoma of the
      salivary glands.
AB  - Mucoepidermoid carcinoma (MEC) is common in the salivary glands, but alterations
      of the p16(INK4a) tumour suppressor gene are largely unknown. The aim of this
      study was to analyse p16(INK4a) gene alterations in MEC, and evaluate their
      significance for carcinogenesis. Thirty-eight salivary glands with MEC and six
      normal salivary glands were studied for p16(INK4a) alterations. In the MEC
      affected group, there were 23.7% (9/38) and 13.2% (5/38) cases of homozygous
      deletion, and 5.3% (2/38) and 2.6% (1/38) cases of point mutation in p16(INK4a)
      exon 1 and exon 2, respectively. Hypermethylation of the p16(INK4a) gene promoter
      was found in 13 cases (13/38, 34.2%). Alterations of the p16(INK4a) gene were not
      found in the normal salivary glands. These findings suggest that the main
      mechanisms of inactivation of the p16(INK4a) gene in MEC of the salivary glands
      are promoter hypermethylation and homozygous deletion.

PMID- 17223312
TI  - Distant bone metastases from carcinoma of the lip: a report of four cases.
AB  - The lip is estimated to be the most frequent location for carcinoma of the oral
      cavity. It occurs more frequently in men, especially those with a history of
      exposure to sunlight. Despite the usually effective management, regional and
      occasionally distant metastases do occur, especially in advanced stages. In this
      retrospective analysis of patients with labial carcinoma presenting with distant
      bone metastases in 1995-2003, the extremely limited number of patients did not
      allow for multivariate data analysis. From a cohort of 415 patients presenting
      with lip lesions, 186 cases were diagnosed as carcinoma and managed accordingly.
      Four patients (2.14%) showed distant bone metastases, one with concurrent
      axillary node metastasis. Patient demographics, tumour characteristics, case
      management and survival were evaluated. The distant metastasis patients were of
      clinical stages II-IV; initial management was wide local excision with
      reconstruction for all cases, with one undergoing concurrent neck dissection and
      one adjuvant radiotherapy. Time for distant bone metastasis was 9-21 months,
      subsequent survival 3-14 months and overall survival 13-35 months. Distant
      metastases from labial carcinoma are rare, not exceeding 2%. Metastasis to bone
      and axillary lymph nodes is exceptionally rare and can be attributed to either
      inadequate initial management or aggressive tumour behaviour.

PMID- 17223313
TI  - Support for association of the A277C single nucleotide polymorphism in human
      vesicular monoamine transporter 1 gene with schizophrenia.

PMID- 17223314
TI  - The +61 A-G polymorphism of the epidermal growth factor gene is not associated
      with occurrence of non-melanocytic skin tumors in transplant recipients.

PMID- 17223315
TI  - Proliferation and differentiation biomarkers in normal human breast skin
      organotypic cultures.

PMID- 17223316
TI  - Characterisation of the phosphatidylinositol synthase gene of Plasmodium species.
AB  - Phosphatidylinositol (PI) is a versatile lipid that not only serves as a
      structural component of cellular membranes, but also plays important roles in
      membrane anchorage of proteins and in signal transduction through distinct
      phosphorylated derivatives of the inositol head group. PI is synthesised by PI
      synthase from CDP-diacylglycerol and myo-inositol. The enzymatic activity in
      Plasmodium falciparum and P. knowlesi has previously been characterised at the
      biochemical level. Here we characterise the PI synthase gene of P. falciparum and
      P. knowlesi. The cDNA sequence identified a highly spliced gene consisting of
      nine exons and encoding a protein of 209 and 207 amino acids, respectively. High
      sequence conservation enabled the prediction of the PI synthase genes of P.
      berghei, P. chabaudi and P. vivax. All Plasmodium PI synthase proteins appear to
      be highly hydrophobic, although no consensus for the number and location of
      distinct transmembrane domains could be detected. The P. falciparum PI synthase
      (PfPIS) gene successfully complemented a Saccharomyces cerevisiae PIS1 deletion
      mutant, demonstrating its enzymatic function. Complementation efficiency was
      dramatically improved when hybrid constructs between N-terminal S. cerevisiae and
      C-terminal P. falciparum sequences were used. Determination of in vitro PIS
      activities of complemented yeast strains confirmed the enzymatic function of the
      Plasmodium protein.

PMID- 17223317
TI  - We know you are in there: conversing with the indigenous gut microbiota.
AB  - The vertebrate gut harbors a coevolved consortium of microbes that plays critical
      roles in the development and health of this organ. Here we discuss recent
      insights into the microbial-host molecular dialogs that shape the digestive
      tracts of the model vertebrates, mice and zebrafish, and consider the parallels
      between vertebrate-microbial mutualisms and the well-studied squid-Vibrio
      symbiosis.

PMID- 17223318
TI  - Is all free time above the minimum inhibitory concentration the same:
      implications for beta-lactam in vivo modelling.
AB  - Previously, ertapenem 50 mg/kg every 6h given subcutaneously to mice achieved a
      similar 24-h cumulative free time above the minimum inhibitory concentration
      (fT>MIC) to 1g every 24h in humans. However, this simplified regimen (SR) does
      not provide a superimposable concentration-time profile to that observed in
      humans, thus allowing concentrations to fluctuate above and below the minimum
      inhibitory concentration (MIC) throughout the 24-h period. Herein, we compared a
      complex regimen (CR; 9 various mg/kg doses over 24 h) providing a near
      superimposable concentration-time profile with the SR to determine implications
      on bacterial kill against eight extended-spectrum beta-lactamase (ESBL)-producing
      isolates over a wide MIC range. The CR resulted in a similar (+/-5%) 24-h
      cumulative fT>MIC to ertapenem 1 g every 24h in humans over an MIC range of 0.032
      mg/L to 16 mg/L. Similar bacterial kill was observed with both regimens against
      all eight ESBL-producing isolates examined. In mouse models, it appears that the
      24-h cumulative fT>MIC and not the distribution of the fT>MIC over 24 h drives
      efficacy.

PMID- 17223319
TI  - Metallo-beta-lactamases as emerging resistance determinants in Gram-negative
      pathogens: open issues.
AB  - The rapid spread of acquired metallo-beta-lactamases (MBLs) among major Gram
      negative pathogens is a matter of particular concern worldwide and primarily in
      Europe, one of first continents where the emergence of acquired MBLs has been
      reported and possibly the geographical area where the increasing diversity of
      these enzymes and the number of bacterial species affected are most impressive.
      This spread has not been paralleled by accuracy/standardisation of detection
      methods, completeness of epidemiological knowledge or a clear understanding of
      what MBL production entails in terms of clinical impact, hospital infection
      control and antimicrobial chemotherapy. A number of European experts in the field
      met to review the current knowledge on this phenomenon, to point out open issues
      and to reinforce and relate to one another the existing activities set forth by
      research institutes, scientific societies and European Union-driven networks.

PMID- 17223320
TI  - Antifungal activities of azole agents against the Malassezia species.
AB  - In this paper, we identified 95 Malassezia isolates by morphological and
      biochemical criteria and assessed the in vitro activity of fluconazole,
      itraconazole, ketoconazole and voriconazole by broth microdilution against these
      species using slightly modified Leeming-Notman medium. The Malassezia isolates
      were identified as M. furfur (74), M. sympodialis (11), M. obtusa (8) and M.
      globosa (2). The modified Leeming-Notman medium used for susceptibility testing
      allowed good growth of Malassezia spp. Visual reading of the minimal inhibitory
      concentration (MIC) was readily achieved until Day 5 of incubation at 32 degrees
      C. Although high MIC values of 16 microg/mL for fluconazole were observed in 9.5%
      of Malassezia isolates, in general these microorganisms were susceptible to all
      drugs studied. Interestingly, one M. globosa isolate showed high MIC values for
      voriconazole, itraconazole and fluconazole. For the 95 strains, the MIC ranges
      were <0.03-4 microg/mL for ketoconazole, <0.03 to >16 microg/mL for voriconazole,
      <0.125 to >64 microg/mL for fluconazole and <0.03-16 microg/mL for itraconazole.
      In summary, the good reproducibility and visual readings obtained using modified
      Leeming-Notman medium suggest that this medium should be proposed for antifungal
      testing of drugs against Malassezia spp.

PMID- 17223322
TI  - The cell cycle hypothesis of Alzheimer's disease: suggestions for drug
      development.
AB  - The cell cycle of hypothesis of neural dysfunction in chronic neurodegenerative
      conditions such as Alzheimer's disease (AD) offers a unified approach to
      understanding both existing and novel strategies for drug development. At the
      present time, a ligand based approach is a pragmatic solution for identifying new
      chemical leads on which to base future discovery and optimisation. We have
      pursued a ligand based approach on the basis of public domain data to identify
      existing compounds capable of abrogating the cell cycle at the G0-G1 interface.
      Selected on this basis, irrespective of the tissue under study, we identified
      several classes of compounds as potential chemical leads. Of these compounds, at
      least ten have already been shown to be neuroprotective in animal models of acute
      neurodegeneration. Such compounds could form the basis of a screening exercise
      after development of suitable screening tools. Progressing of chemical leads
      through such an approach will be more efficient if future leads display relevant
      "drug-like" properties. Further, drug development in this arena should take
      account of the special concerns raised by targeting an elderly population. This
      will involve accounting for frequent polypharmacy in the aging population, and
      age-related alterations in physiology.

PMID- 17223321
TI  - Chronic wasting disease.
AB  - Until recently, chronic wasting disease of cervids, the only prion disease
      affecting wildlife, was believed to be geographically concentrated to Colorado
      and Wyoming within the United States. However, increased surveillance has
      unveiled several additional pockets of CWD-infected deer and elk in 12 additional
      states and 2 Canadian provinces. Deer and elk with CWD have extensive aggregates
      of PrP(Sc) not only in the central nervous system, but also in peripheral
      lymphoid tissues, skeletal muscle, and other organs, perhaps influencing prion
      shedding. Indeed, CWD is transmitted efficiently among animals by horizontal
      routes, although the mechanism of spread is unknown. Genetic polymorphisms in the
      Prnp gene may affect CWD susceptibility, particularly at codon 225 (S/F) in deer
      and codon 132 (M/L) in elk. Since CWD infects free-ranging animals and is
      efficiently spread, disease management will be a challenge.

PMID- 17223323
TI  - ASB-1, a germline-specific isoform of mitochondrial ATP synthase b subunit, is
      required to maintain the rate of germline development in Caenorhabditis elegans.
AB  - The developmental timing of all types of cells must be synchronized and spatially
      coordinated to achieve the organized development of a multicellular organism.
      Previously, we found RNAi of asb-1, encoding a germline-specific isoform of
      mitochondrial ATP synthase b subunit, caused 100% penetrant sterility in
      Caenorhabditis elegans. ATP synthase is one of the five complexes of the
      mitochondrial respiratory chain, and defects in some of the components of the
      chain are known to slow the growth and extend the lifespan of worms. We found
      that development of asb-1 mutant germ line was not arrested at any stage, but did
      slow to half the rate of wild type, whereas the rate of somatic development was
      the same in asb-1 mutants as that of wild type, indicating that asb-1 is required
      to maintain the rate of germline development but has no effect on somatic
      development. Among ATP synthase subunit genes, RNAi of asg-1, encoding a germline
      specific isoform of the g subunit, also caused asb-1-like sterility, indicating
      that some other germline-specific components are also required to maintain the
      rate of germline development. Both asb-1 and asg-1 are located on autosomes while
      they possess counterparts, asb-2 and asg-2, respectively, on X chromosome, which
      are both required for somatic development. Chromosomal locations of the genes may
      be the basis of the segregation of germline/somatic functions of each gene, as
      were demonstrated for other autosomal/X-linked duplicated gene pairs.

PMID- 17223324
TI  - Targeted ablation of beta cells in the embryonic zebrafish pancreas using E. coli
      nitroreductase.
AB  - In order to generate a zebrafish model of beta cell regeneration, we have
      expressed an Escherichia coli gene called nfsB in the beta cells of embryonic
      zebrafish. This bacterial gene encodes a nitroreductase (NTR) enzyme, which can
      convert prodrugs such as metronidazole (Met) to cytotoxins. By fusing nfsB to
      mCherry, we can simultaneously render beta cells susceptible to prodrug and
      visualize Met dependent cell ablation. We show that the neighboring alpha and
      delta cells are unaffected by prodrug treatment and that ablation is beta cell
      specific. Following drug removal and 36h of recovery, beta cells regenerate.
      Using ptf1a morphants, it is clear that this beta cell recovery occurs
      independently of the presence of the exocrine pancreas. Also, by using
      photoconvertible Kaede to cell lineage trace and BrdU incorporation to label
      proliferation, we investigate mechanisms for beta regeneration. Therefore, we
      have developed a unique resource for the study of beta cell regeneration in a
      living vertebrate organism, which will provide the opportunity to conduct large
      scale screens for pharmacological and genetic modifiers of beta cell
      regeneration.

PMID- 17223326
TI  - [Vitiligo].

PMID- 17223325
TI  - Polarizability and Kerr constant of proteins by boundary element methods.
AB  - A precise implementation of the boundary element method has been applied to the
      computation of the polarizability and the Kerr constant of eight soluble
      proteins. The method is demonstrated to be accurate and precise by comparison
      with analytical values for spheroids. Two different integral equations have been
      solved: (1) an exact equation with explicit dielectric constant dependence, and
      (2) an exact equation for a metallic body. The dielectric dependence for the
      metallic body case is built in with a generalization of the ellipsoid formula.
      Both methods agree quantitatively with each other for low relative dielectric
      constants. A full tensor expression for the Kerr constant yields perfect
      agreement with experiment for some proteins and badly under reports for the rest.
      The protein structure is obtained from a crystallographic database and is assumed
      rigid throughout the TEB measurement. Electrolyte effects are neglected. The Kerr
      constant is dominated by the protein dipole moment and is quite sensitive to the
      orientation of the dipole moment relative to the principal axes of the
      polarizability tensor. Several possible reasons for the large discrepancy between
      some computed and measured values are discussed.

PMID- 17223327
TI  - Chemical composition and antimicrobial activity of volatile compounds of Tamarix
      boveana (Tamaricaceae).
AB  - The chemical composition of the Tamarix boveana volatile oils obtained from the
      whole aerial part, flowers, leaves and stems by steam distillation was analysed
      using gas chromatograph (GC)-flame ionization detectors (FID) and GC-MS. Sixty
      two components were identified. Hexadecanoic acid (18.14%), docosane (13.34%),
      germacrene D (7.68%), fenchyl acetate (7.34%), Benzyl benzoate (4.11%) were found
      to be the major components in the whole aerial parts. This composition differed
      according to the tested part: 2.4 Nonadienal was the main compound in the flowers
      (12.13%) while germacrene D was the major component in leaves (31.43%) and
      hexadecanoic acid in the stems (13.94%). To evaluate in vitro antimicrobial
      activity, all volatile oils were tested against six Gram-positive and Gram
      negative bacteria and four fungi. The T. boveana volatile oils exhibited an
      interesting antibacterial activity against all strains tested except Pseudomonas
      aeruginosa but no antifungal activity was detected.

PMID- 17223328
TI  - Does beta-blocker treatment influence central sleep apnoea?
AB  - Chronic severe heart failure is frequently associated with disturbances in the
      central control of breathing. During wakefulness, central breathing disorders
      could be ameliorated with beta-blocker treatment, but nothing is known about the
      effects of beta-blockers on the control of breathing during sleep. This study
      intends to determinate the prevalence and severity of nocturnal apnoeas and
      hypopnoeas in heart failure patients treated with or without metoprolol or
      carvedilol. Fifty consecutive patients with dilated cardiomyopathy in NYHA class
      II-IV with a left ventricular ejection fraction (LVEF) of 35% or below were
      studied with full polysomnography over one night. The mean Apnoea-Hypopnoea Index
      of beta-blocker free patients was 19.8+/-14.2 versus 7.4+/-8.5 (p<0.05) and 8.7+/
      8.1 (p<0.05) in patients treated with metoprolol or carvedilol, respectively. The
      arousal index, sleep quality, and daytime sleepiness were improved in similar
      magnitude. CONCLUSION: Long-term treatment of patients with advanced chronic
      heart failure with sufficient doses of metoprolol or carvedilol is associated
      with a lower prevalence and severity of central sleep apnoea (CSA).

PMID- 17223329
TI  - Long-term outcome and effects of oral bosentan therapy in Taiwanese patients with
      advanced idiopathic pulmonary arterial hypertension.
AB  - STUDY DESIGN: We report on the long-term outcome and effects of bosentan
      treatment in Taiwanese patients with advanced (functional class III or IV)
      idiopathic pulmonary arterial hypertension (IPAH). MATERIALS AND METHODS: IPAH
      patients on stable bosentan therapy for more than 12 months and regularly
      monitored were eligible for this prospective uncontrolled study. Patients were
      evaluated for several clinical parameters, both measured at the time of
      initiation of bosentan therapy and after 12 months on therapy: New York Heart
      Association functional class (NYHA FC), change in 6-min walk distance (6MWD),
      right ventricle ejection fraction (RVEF), cardiothoracic ratio (CTR), and
      pulmonary functional status. RESULTS: Twelve of 15 patients met eligibility
      requirements and were enrolled. Their mean age was 37.6+/-12.9 years and 92% were
      female. Six (50%) patients were in NYHA FC IV and the others were in NYHA FC III
      at baseline. Three (25%) patients were chronic hepatitis C virus (HCV) carriers,
      with normal liver function. After 12 months of bosentan treatment, 6-MWD, RVEF,
      and pulmonary function all increased significantly. CTR and NYHA FC both
      decreased significantly. Oral bosentan was well tolerated and there was no
      episode of liver dysfunction that required adjustment of the bosentan dosage or
      discontinuance of therapy. CONCLUSION: Long-term treatment with oral bosentan
      appears to have beneficial effects on functional status, exercise capacity, right
      heart function, and pulmonary function in Taiwanese patients with advanced IPAH,
      regardless of whether or not they presented with chronic HCV infection.

PMID- 17223330
TI  - Carbamazepine in asthma: first do no harm!

PMID- 17223332
TI  - Serial samples of breath ethane can also be analyzed by gas-chromatography.

PMID- 17223333
TI  - Pesticide detection with a liposome-based nano-biosensor.
AB  - Monitoring of the organophosphorus pesticides dichlorvos and paraoxon at very low
      levels has been achieved with liposome-based nano-biosensors. The enzyme
      acetylcholinesterase was effectively stabilized within the internal nano
      environment of the liposomes. Within the liposomes, the pH sensitive fluorescent
      indicator pyranine was also immobilized for the optical transduction of the
      enzymatic activity. Increasing amounts of pesticides lead to the decrease of the
      enzymatic activity for the hydrolysis of the acetylcholine and thus to a decrease
      in the fluorescent signal of the pH indicator. The decrease of the liposome
      biosensors signal is relative to the concentration of dichlorvos and paraoxon
      down to 10(-10)M levels. This biosensor system has been applied successfully to
      the detection of total toxicity in drinking water samples. Also a colorimetric
      screening device for pesticide analysis has been evaluated.

PMID- 17223334
TI  - Optimizing the formulation of a myoglobin molecularly imprinted thin-film polymer
      -formed using a micro-contact imprinting method.
AB  - Thin-film myoglobin molecularly imprinted polymers have been fabricated using a
      micro-contact approach. By initially selecting the cross-linker on the basis of
      it having a minimal recognition for the template and using this as a starting
      point for functional monomer selection, we have produced myoglobin imprinted
      polymers with exceptionally high selectivities. The affinity of the polymers, for
      myoglobin, when prepared with a variety of different cross-linkers and no
      functional monomer was evaluated. Of these, tetraethylene glycol dimethacrylate
      (TEGDMA) exhibited the lowest affinity for the template species. Methyl
      methacrylate (MMA) was chosen as the functional monomer as when it was used in
      conjunction with TEGDMA, it exhibited maximum selectivity for the template
      compared to polymers made with other functional monomers. With a MMA to TEGDMA
      ratio of 1 to 3, the myoglobin molecularly imprinted polymer adsorbed 15.03+/
      0.89 x 10(-11)mole/cm(2) of template from a 5.68 x 10(-7)M myoglobin solution,
      compared to 2.58+/-0.02 x 10(-11)mole/cm(2) for a polymer of similar composition,
      but formed in the absence of a template. Various washing conditions, using
      alkaline media to remove the template, were investigated. An extraction solvent
      comprising 2 wt.% SDS and 0.6 wt.% NaOH used at 80 degrees C for 30 min was shown
      to give the highest imprinting factor i.e. 5.83 with 72.82% myoglobin removal.
      The saturation kinetics of template binding to the thin-film MIP were examined
      and found to display a simple two-phase profile typical of non-cooperative
      binding. A Scatchard binding plot showed the dissociation constant (K(d)) for the
      specific binding phase to be 3.4 x 10(-7)M and the binding site capacity to be
      7.24 x 10(-11)mole/cm(2). For the non-specific binding phase, K(d) was found to
      be 1.355 x 10(-5)M and the binding site capacity was determined as 9.62 x 10(
      10)mole/cm(2). Selectivity experiments were carried out in both single protein
      and binary protein systems all using a total protein concentration of 5.68 x 10(
      7)M. The molar ratio of adsorbed myoglobin to IgG, HSA and hemoglobin was found
      to 115.5, 230.9 and 2.5, respectively. While, in binary competition systems,
      myoglobin selectivity to IgG, HSA and hemoglobin was, respectively, 94.18, 98.21
      and 61.09%. Rebinding in natural biological matrices, i.e. human serum or urine,
      showed the imprinted films to have significantly greater uptake than non
      imprinted films. Re-binding in undiluted urine was found to be a facile process,
      with the imprinting factor, i.e. the ratio of MIP to NIP binding, being
      determined as 37.4.

PMID- 17223335
TI  - Real-time detection of Escherichia coli O157:H7 sequences using a circulating
      flow system of quartz crystal microbalance.
AB  - A DNA piezoelectric biosensing method for real-time detection of Escherichia coli
      O157:H7 in a circulating-flow system was developed in this study. Specific probes
      [a 30-mer oligonucleotide with or without additional 12 deoxythymidine 5'
      monophosphate (12-dT)] for the detection of E. coli O157:H7 gene eaeA, synthetic
      oligonucleotide targets (30 and 104 mer) and PCR-amplified DNA fragments from the
      E. coli O157:H7 eaeA gene (104 bp), were used to evaluate the efficiency of the
      probe immobilization and hybridization with target DNA in the circulating-flow
      quartz crystal microbalance (QCM) device. It was found that thiol modification on
      the 5'-end of the probes was essential for probe immobilization on the gold
      surface of the QCM device. The addition of 12-dT to the probes as a spacer,
      significantly enhanced (P<0.05) the hybridization efficiency (H%). The results
      indicate that the spacer enhanced the H% by 1.4- and 2-fold when the probes were
      hybridized with 30- and 104-mer targets, respectively. The spacer reduced steric
      interference of the support on the hybridization behavior of immobilized
      oligonucleotides, especially when the probes hybridized with relatively long
      oligonucleotide targets. The QCM system was also applied in the detection of PCR
      amplified DNA from real samples of E. coli O157:H7. The resultant H% of the PCR
      amplified double-strand DNA was comparable to that of the synthetic target T
      104AS, a single-strand DNA. The piezoelectric biosensing system has potential for
      further applications. This approach lays the groundwork for incorporating the
      method into an integrated system for rapid PCR-based DNA analysis.

PMID- 17223336
TI  - Thermodynamic and kinetic analysis of the interaction between hepatitis B surface
      antibody and antigen on a gold electrode modified with cysteamine and colloidal
      gold via electrochemistry.
AB  - Hepatitis B surface antibody (HBsAb) was immobilized to the surface of a gold
      electrode modified with cysteamine and colloidal gold as matrices to detect
      hepatitis B surface antigen (HBsAg). Differential pulse voltammetry (DPV) method
      was used for the investigation of the specific interaction between the
      immobilized HBsAb and HBsAg in solution, which was followed as a change of peak
      current in DPV with time. With the modified gold electrode, the differences in
      affinity of HBsAb with HBsAg at the temperatures of 37 and 40 degrees C were
      easily distinguished and the kinetic rate constants (k(ass) and k(diss)) and
      kinetic affinity constant K were determined from the curves of current versus
      time. In addition, the thermodynamic constants, DeltaG, DeltaH and DeltaS, of the
      interaction at 37 degrees C were calculated, which were -56.65, -64.54 and -25.45
      kJ mol(-1), respectively.

PMID- 17223337
TI  - Sandwich electrochemical immunoassay for the detection of Staphylococcal
      enterotoxin B based on immobilized thiolated antibodies.
AB  - A new approach for the sensitive detection of Staphylococcal enterotoxin B (SEB)
      is presented based upon an electrochemical enzymatic immunoassay that utilizes
      thiolated antibodies immobilized on a gold surface. This method relies on the use
      of amine- or sulfhydryl-reactive heterobifunctional cross-linkers for the
      introduction of 2-pyridyl-disulfide groups to the antibody. The disulfide
      containing linkages are subsequently cleaved with a suitable reducing agent, such
      as dithiothreitol (DTT), and the thiolated antibody-gold bond is covalently
      formed on a gold working electrode. Various cross-linking agents for
      immobilization of the capture antibody onto the gold electrode were investigated
      and compared. Factors influencing the thiolation and immobilization were
      investigated and optimized. The feasibility of such antibody immobilization and
      the subsequent sandwich enzyme immunoassay is demonstrated for the sensitive
      detection of SEB. The detection limit estimated from a representative dose
      response curve is 1 ng/mL, corresponding to 5 pg in a 5-microL sample. Coupling
      the specificity of immunoassays with the sensitivity and low detection limits of
      electrochemical detection shows real promise for future sensing technology in
      enabling the development of single-use disposable devices.

PMID- 17223339
TI  - Targeting neuronal dysfunction and receptor imaging.
AB  - The sympathetic nervous system has great influence on cardiovascular physiology,
      and the importance of cardiac innervation abnormalities in the physiopathology of
      various cardiac diseases has been emphasized. Cardiac neurotransmission imaging
      with single-photon emission computed tomography (SPECT) allows in vivo assessment
      of the myocardial nervous system. At present, the most commonly used SPECT tracer
      to assess cardiac neurotransmission is metaiodobenzylguanidine labelled with
      iodine-123 ((123)I-MIBG). In patients with heart transplantation, ischemic heart
      disease, dysautonomias and drug-induced cardiotoxicity, assessment of neuronal
      function can help characterise the disease and improve the prognostic
      stratification. Cardiac (123)I-MIBG scintigraphy allows autonomic neuropathy to
      be detected in the early stages of diabetes mellitus. In patients with heart
      failure, the assessment of cardiac sympathetic activity has important prognostic
      implications. Future directions in cardiac sympathetic neurotransmission include
      the development of new tracers, targeting of second-messenger molecules and early
      assessment of cardiac neurotransmission in genetically predisposed subjects for
      prevention of heart failure.

PMID- 17223338
TI  - Target delivery in a microfluidic immunosensor.
AB  - A study is presented that examines the effect of microfluidic mixing elements on
      direct and sandwich assays performed in microchannels. Patterned grooves were
      embossed in the top of microchannels made in PDMS using soft lithography. The
      grooves redirected the fluid flowing in the channel, enhancing delivery of the
      target from the bulk fluid to the surface and preventing the formation of a
      depletion layer at the surface. Comparing assays in grooved and plain channels
      demonstrated that the mixers improved assay results by 26-46%. A computational
      flow analysis showed that the grooves caused virtual particles in the bulk flow
      to come close to the surface ( approximately 11 microm) which is consistent with
      the signal increase seen experimentally. Direct assays for several concentrations
      of CY5-labeled biotin were performed in the microchannels. The mixers also
      improved signal intensity in sandwich assays for botulinum toxin which required
      mixing of the reagents as well as the direction of the target to the surface.

PMID- 17223340
TI  - 2-(3'-Hydroxypropylidene)-1alpha-hydroxy-19-norvitamin D compounds with truncated
      side chains.
AB  - Our recent studies with 2-(3'-hydroxypropylidene) analogs of 1alpha,25-dihydroxy
      19-norvitamin D(3) showed that this 2-substituent creates compounds with very
      potent biological activity. In the continuing search for vitamin D compounds with
      selective activity profiles, we prepared a series of 1alpha-hydroxy-19-norvitamin
      D analogs characterized by the presence of a 3'-hydroxypropylidene substituent at
      C-2 and a truncated side chain. These vitamin D compounds were efficiently
      prepared using convergent syntheses. The C,D-fragments, namely the Grundmann
      ketones 19, 20, 27, 36 and 37 were synthesized from the known 8beta-benzoyloxy-22
      aldehydes 12 and 29. These hydrindanones were subjected to Lythgoe type Wittig
      Horner coupling with phosphine oxide 21, prepared by us previously, and after
      hydroxyl deprotection the set of 19-norvitamins 7-11 was successfully obtained.
      According to our expectations, all analogs (with an exception of the 20R-compound
      7) have pronounced in vitro activity. When compared to the natural hormone
      1alpha,25-(OH)(2)D(3) (1), they show the same or only slightly reduced affinity
      for the vitamin D receptor while being similarly effective as 1 in
      differentiation of HL-60 cells into monocytes.

PMID- 17223341
TI  - Differential role of two VDR coactivators, DRIP205 and SRC-3, in keratinocyte
      proliferation and differentiation.
AB  - Cell programs such as proliferation and differentiation involve the selective
      activation and repression of gene expression. The vitamin D receptor (VDR),
      through 1,25(OH)(2)D(3), controls the proliferation and differentiation of
      keratinocytes. Previously, we have identified two VDR binding coactivator
      complexes. In proliferating keratinocytes VDR bound preferentially to the DRIP
      complex, whereas in differentiated keratinocytes the SRC complex was preferred.
      We proposed that different coactivators are required for sequential gene
      regulation in the transition from proliferation to differentiation. Here we
      examined the roles of DRIP205 and SRC-3 in this transition. Silencing of DRIP205
      and VDR caused hyperproliferation of keratinocytes, demonstrated by increased XTT
      and BrdU incorporation. SRC-3 silencing, on the other hand, did not have an
      effect on proliferation. In contrast, SRC-3 as well as DRIP205 and VDR silencing
      blocked keratinocyte differentiation as shown by decreased expression of keratin
      1 and filaggrin. These results are consistent with the differential localization
      of DRIP205 and SRC-3 in skin. These results indicate that DRIP205 is required for
      keratinocyte proliferation. Both DRIP205 and SRC-3 are required for the
      keratinocyte differentiation. These results support the concept that the
      selective use of coactivators by VDR underlies the selective regulation of gene
      expression in keratinocyte proliferation and differentiation.

PMID- 17223342
TI  - Role of the vitamin D receptor in hair follicle biology.
AB  - The vitamin D receptor (VDR) is expressed in numerous cells and tissues,
      including the skin. The critical requirement for cutaneous expression of the VDR
      has been proven by investigations in mice and humans lacking functional
      receptors. These studies demonstrate that absence of the VDR leads to the
      development of alopecia. The hair follicle is formed by reciprocal interactions
      between an epidermal placode, which gives rise to the hair follicle keratinocytes
      and the underlying mesoderm which gives rise to the dermal papilla. Hair follicle
      morphogenesis ends the second week of life in mice. Studies in VDR null mice have
      failed to demonstrate a cutaneous abnormality during this period of hair follicle
      morphogenesis. However, VDR null mice are unable to initiate a new hair cycle
      after the period of morphogenesis is complete, therefore, do not grow new hair.
      Investigations in transgenic mice have demonstrated that restricted expression of
      the VDR to keratinocytes is capable of preventing alopecia in the VDR null mice,
      thus demonstrating that the epidermal component of the hair follicle requires VDR
      expression to maintain normal hair follicle homeostasis. Studies were then
      performed to determine which regions of the VDR were required for these actions.
      Investigations in mice lacking the first zinc finger of the VDR have demonstrated
      that they express a truncated receptor containing an intact ligand binding and
      AF2 domain. These mice are a phenocopy of mice lacking the VDR, thus demonstrate
      the critical requirement of the DNA binding domain for hair follicle homeostasis.
      Transgenic mice expressing VDRs with mutations in either the ligand-binding
      domain or the AF2 domain were generated. These investigations demonstrated that
      mutant VDRs incapable of ligand-dependent transactivation were able to prevent
      alopecia. Investigations are currently underway to define the mechanism by which
      the unliganded VDR maintains hair follicle homeostasis.

PMID- 17223343
TI  - Synthesis and biological evaluation of a des-C,D-analog of 2-methylene-19-nor
      1alpha,25-(OH)2D3.
AB  - Structure-activity studies directed at novel Vitamin D compounds of potential
      therapeutic value has long attracted an attention of numerous research groups. To
      date more than 3000 analogs of the natural hormone 1alpha,25-dihydroxyvitamin
      D(3) (1) have been synthesized and tested. As a continuation of our studies on 19
      norvitamin D compounds we have obtained (20S)-des-C,D-2-methylene-1alpha,25
      dihydroxy-19-norvitamin D(3) (6) and examined its biological activity. This
      Vitamin D compound was efficiently prepared in a convergent synthesis. The
      "upper" fragment was synthesized starting with methyl (R)-(-)-3-hydroxy-2
      methylpropionate (9). The key synthetic step involved Lythgoe type Wittig-Horner
      coupling of the protected hydroxy aldehyde 19 with the phosphine oxide 20. The
      prepared Vitamin D analog 6 exhibited limited binding ability to the rat
      intestinal Vitamin D receptor being ca. 80 times less potent when compared to the
      natural hormone 1. Although the analog 6 did retain some cell differentiating and
      transcriptional activities, preliminary in vivo tests do not show any activity of
      this analog in animals.

PMID- 17223344
TI  - Alanine scanning mutational analysis of the ligand binding pocket of the human
      Vitamin D receptor.
AB  - We achieved exhaustive alanine scanning mutational analysis of the amino acid
      residues lining the ligand binding pocket of the Vitamin D receptor to
      investigate the mechanism of the ligand recognition by the receptor. This is the
      first exhaustive analysis in the nuclear receptor superfamily. Our results
      demonstrated the role and importance of all the residues lining the ligand
      binding pocket. In addition, this analysis was found to indicate ligand-specific
      ligand-protein interactions, which have key importance in determining the
      transactivation potency of the individual ligands. Thus, the analysis using 1beta
      methyl-1alpha,25-dihydroxyvitamin D(3) revealed the specific van der Waals
      interactions of 1beta-methyl group with the receptor.

PMID- 17223345
TI  - CYP2R1-, CYP27B1- and CYP24-mRNA expression in German type 1 diabetes patients.
AB  - 1,25(OH)(2)D(3) and 25(OH)D(3) have been associated with type 1 diabetes. Diverse
      enzymes are involved in the synthesis of these metabolites: the 25-Vitamin-D
      hydroxylase (CYP2R1), the 25-hydroxyvitamin-D(3)-1-alpha-hydroxylase (CYP27B1)
      and the 25(OH)D(3)-24-hydroxylase (CYP24) among others. Serum levels of
      25(OH)D(3) and 1,25(OH)(2)D(3) were investigated in type 1 diabetes patients
      (n=173) and the mRNA expression of the CYP2R1, CYP27B1 and CYP24 genes in type 1
      diabetes patients (n=33) and healthy controls (n=23). These parameters were
      correlated with the -1260 (C/A) polymorphism in the CYP27B1 gene. Lower
      expression of CYP27B1 mRNA in comparison with healthy controls (1.7165 versus
      1.7815, P=0.0268) was found. Additionally, patients carrying the genotype CC
      possessed a reduced amount of CYP27B1 mRNA compared to healthy controls (1.6855
      versus 1.8107, respectively, P=0.0220). The heterozygosity rate of the -1260 C/A
      polymorphism was more frequent in patients with normal levels of 1,25(OH)(2)D(3)
      (> or =19.9 pmol/ml) than in whose with a level of less than 19.9 pmol/ml (46.7%
      versus 22.2%, P=0.0134). No correlation with serum levels of 25(OH)D(3) was
      found. Thus, CYP27B1 gene could play a functional role in the pathogenesis of
      type 1 diabetes through modulation of its mRNA expression and influence serum
      levels of 1,25(OH)(2)D(3) via the -1260 C/A polymorphism.

PMID- 17223346
TI  - An exploration of the function of the triceps surae during normal gait using
      functional electrical stimulation.
AB  - Gastrocnemius and soleus have a common tendon and both are active during stance
      phase, where they are thought to arrest and control tibial advance. Soleus is
      associated with the production of an extending moment at the knee. The two-joint
      gastrocnemius, which crosses the knee joint, will have an additional contribution
      to the knee flexors. Recent work using induced acceleration analysis (IAA) has
      demonstrated distinct differences between the actions of gastrocnemius and
      soleus. This study aims to use gait analysis to provide in vivo examination of
      these theoretical predictions. Functional electrical stimulation (FES) was chosen
      to provide a perturbation in muscle force, a close physical analogue to the
      theoretical predictions of IAA. Five adult male subjects, with no gait problems,
      participated. Each had gastrocnemius and soleus stimulated at three different
      timings during normal gait, while 3D gait data were collected. The order of
      testing was randomised and unstimulated trials were randomly interspersed to act
      as a control. The results show very different actions for soleus (ankle
      plantarflexing/knee extending) and gastrocnemius (ankle dorsiflexing/knee
      flexing) in stance phase. The counterintuitive nature of the action of
      gastrocnemius suggests that further clinical and biomechanical investigation into
      this muscle's function is required. The actions of both muscles at the knee
      confirm published IAA predictions. In vivo evidence such as this gives greater
      confidence when using model predictions. The approach adopted in this study could
      eventually be extended to other muscles and patient populations.

PMID- 17223347
TI  - High-throughput assay for the identification of Hsp90 inhibitors based on Hsp90
      dependent refolding of firefly luciferase.
AB  - Previously, we have demonstrated that the renaturation of heat denatured firefly
      luciferase is dependent upon the activity of Hsp90 in rabbit reticulocyte lysate.
      Here, we demonstrate that this assay may identify inhibitors that obstruct the
      chaperone activity of Hsp90 either by direct binding to its N-terminal or C
      terminal nucleotide binding sites or by interference with the ability of the
      chaperone to switch conformations. The assay was adapted and optimized for high
      throughput screening. Greater than 20,000 compounds were screened to demonstrate
      the feasibility of using this assay on a large scale. The assay was reproducible
      (av Z-factor=0.62) and identified 120 compounds that inhibited luciferase
      renaturation by greater than 70% at a concentration of 12.5 microg/mL. IC50
      values for twenty compounds with varying structures were determined for
      inhibition of luciferase refolding and in cell-based assays for Hsp90 inhibition.
      Several compounds had IC50 values <10 microM and represent a number of new lead
      structures with the potential for further development and optimization as potent
      Hsp90 inhibitors.

PMID- 17223348
TI  - Modified expression of Mts1/S100A4 protein in C6 glioma cells or surrounding
      astrocytes affects migration of tumor cells in vitro and in vivo.
AB  - The calcium-binding Mts1/S100A4 protein plays an important role in motility and
      metastatic activity of tumor cells. Recently we showed that Mts1/S100A4 is
      expressed in white matter astrocytes and influences their migration in vitro and
      in vivo. Here, we have investigated the role of Mts1/S100A4 expression in C6
      glioma cells or surrounding astrocytes for migration of C6 cells on astrocytes,
      using short interference (si) RNA to silence Mts1/S100A4 expression. We find that
      in vitro, the migration of Mts1/S100A4 expressing and silenced C6 cells on
      astrocytes is predominantly dependent on the expression of Mts1/S100A4 in
      astrocytes, i.e. C6 cells preferably migrate on Mts1/S100A4-silenced astrocytes.
      In vivo, Mts1/S100A4-positive C6 cells preferably migrate in white matter. In
      contrast Mts1/S100A4-silenced C6 cells avoid white matter and migrate in gray
      matter and meninges. Thus, the migration pattern of C6 cells is affected by their
      intrinsic Mts1/S100A4 expression as well as Mts1/S100A4 expression in astrocytes.
      To investigate if Mts1/S100A4 has a significant role on brain tumor progression,
      we made quantitative RT-PCR analysis for the expression of S100A4/Mts1 in various
      grades of astrocytic tumors. Our data showed that high-grade glioblastomas
      express higher amount of S100A4/Mts1 than low-grade astrocytic tumors.

PMID- 17223349
TI  - RETRACTED: Isolation, characterization and expression of a gene from Brassica
      napus encoding a LIM-domain protein.
AB  - This article has been retracted consistent with Elsevier Policy on Article
      Withdrawal. Please see http://www.elsevier.com/locate/withdrawalpolicy The
      Publisher apologizes for any inconvenience this may cause.

PMID- 17223350
TI  - Successful radiofrequency ablation determines atrio-ventricular remodelling and
      improves systo-diastolic function at tissue Doppler-imaging.
AB  - BACKGROUND: Clinical, echocardiographic results and determinants of atrial
      fibrillation (AF) recurrence following AF ablation during mitral valve surgery
      (AFAMVS) were evaluated. METHODS: Fifty-two patients undergoing radiofrequency
      AFAMVS between January 2003 and December 2005, underwent serial
      echocardiographies with tissue Doppler imaging to assess atrio-ventricular
      function. Recurrence of AF, hospital readmission, episodes of congestive heart
      failure (CHF) were recorded. Predictors for AF-recurrence were evaluated.
      RESULTS: At a 29.5+/-8.6 months of follow-up (100% complete), 78.8% patients were
      in sinus rhythm (SR). Freedom from AF-recurrence was 64.6+/-0.76%, from hospital
      readmission 88.9+/-0.47%, from CHF 91.6+/-0.63%. SR-patients demonstrated better
      freedom from hospital readmission (97.4 vs 60.6%; p=0.0003) and from CHF (100 vs
      72.7%; p=0.008) during follow-up. At follow-up SR-patients demonstrated left
      atrial (preoperative 5.8+/-0.8 cm vs follow-up 5.1+/-0.9; p=0.013) and
      ventricular reverse remodelling (preoperative LVDd 5.7+/-1.1cm vs follow-up 5.2+/
      1.1; p=0.048 - preoperative LVDs 4.0+/-1.4 vs follow-up 3.6+/-1.1; p=0.036). E/A
      ratio was normal in 73.1% (92.7% of SR-patients). TDI at the level of the left
      lateral annulus showed an improved left ventricular systole (Sm), and diastole
      (Em, E/Em) of SR-patients, compared with AF-patients (Sm 9.40+/-1.74 vs 7.72+/
      1.5, p=0.0001; Em: 10.45+/-1.98 vs 7.68+/-0.72, p=0.001; E/Em: 0.07+/-0.02 vs
      0.10+/-0.04, p=0.0001). Large preoperative atrial diameter (OR=5.81; p=0.002),
      preoperative NYHA-IV (OR=3.55; p=0.001), high diuretics at discharge (OR=1.27;
      p=0.03), tricuspid insufficiency at follow-up (OR=2.31; p=0.02) were independent
      predictors of AF-recurrence. CONCLUSIONS: Radiofrequency AFAMVS achieves 78.8% of
      SR recovery. Maintenance of SR improves clinic, haemodynamic and
      echocardiographic endpoints. Pre- and post-operative cardiac failure is the main
      determinant of AF-recurrence.

PMID- 17223351
TI  - The feasibility of three-dimensional displays of the thorax for preoperative
      planning in the surgical treatment of lung cancer.
AB  - OBJECTIVE: Three-dimensional (3D) displays of anatomic structures have become
      feasible for preoperative planning in some surgical procedures. There have been
      no reports, however, on the use of 3D displays for surgical treatment of lung
      cancer. We hypothesized that 3D displays of the thorax are useful for
      preoperative planning for lung cancer. METHODS: Based on virtual reality
      technologies, we rendered 3D displays of the thorax from two-dimensional (2D)
      computed tomographic (CT) images of six anonymous patients, some of whom
      underwent surgical removal of lung cancer. For determining the resectability of
      lung cancer, we tested 17 participants with varying degrees of surgical skills to
      view 3D displays and read 2D CT images of these thoracic cavities in a randomized
      order. We measured their performance in terms of the accuracy of predicted
      resectability, the confidence of their prediction, planning time used, and
      workload experienced. RESULTS: The results demonstrated that viewing 3D displays
      of thoracic cavities has significant advantages over reading 2D CT images in
      determining the resectability of lung cancer: increasing the accuracy of
      predicted resectability by about 20%, enhancing the confidence of the prediction
      by about 20%, decreasing planning time by about 30%, and reducing workload by
      about 50%. All participants preferred viewing 3D displays to reading 2D CT images
      for preoperative planning. Junior residents found 3D displays of thoraces more
      useful than senior residents. CONCLUSIONS: It is feasible to use 3D displays of
      the thorax for preoperative planning in treating lung cancer. Using 3D displays
      in surgical treatment of lung cancer has potential benefits, once the technique
      is perfected.

PMID- 17223352
TI  - Institutional experience with extracorporeal membrane oxygenation in lung
      transplantation.
AB  - BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is currently accepted in
      lung transplantation either to bridge patients to transplantation or to treat
      postoperatively arising severe primary graft failure. Based on promising initial
      experiences we have since 2001 implemented ECMO as the standard of intraoperative
      extracorporeal support in lung transplantation (LuTX) patients with haemodynamic
      or respiratory instability with the potential to prolong ECMO support into the
      perioperative period. The aim of this paper is to summarise our total experience
      with the use of ECMO in LuTX. METHODS: We retrospectively reviewed all 306
      patients undergoing primary lung transplantation from 1/2001 to 1/2006 with
      regard to the different forms of ECMO use. Results of all patients requiring ECMO
      were compared to those without ECMO during the observation period. RESULTS: ECMO
      was used in 147 patients in total. Two patients were bridged to transplantation.
      A total of 130 patients received intraoperative ECMO support. In 51 of these
      patients ECMO was prolonged into the perioperative period. Five of these patients
      required ECMO support again in the postoperative period due to graft dysfunction.
      Contrary cardiopulmonary bypass was used in 27 patients mainly with concomitant
      cardiac defects. Eleven of these patients needed therapeutic ECMO in the further
      course. A total of 149 patients without relevant risk factors were transplanted
      without any intraoperative extracorporeal support. Six of these patients required
      ECMO support in the postoperative period for treatment of primary graft
      dysfunction. Overall 3-month, 1-year and 3-year survival rates were 88.6%, 82.1%
      and 74.63%. The mentioned survival rates were 85.4%, 74.2% and 67.6% in the
      intraoperative+/-prolonged ECMO group; 93.5%, 91.9% and 86.5% in the no support
      group and 74.0%, 65.9% and 57.7% in the CPB group. CONCLUSION: ECMO is a valuable
      tool in lung transplantation providing the potential to bridge patients to
      transplantation, to replace CPB with at least equal results and to overcome
      severe postoperative complications. Favourable survival rates can be achieved
      despite the fact that ECMO is used in the more complex patient population
      undergoing lung transplantation as well as to overcome already established severe
      complications.

PMID- 17223353
TI  - Positive and negative ion electrospray tandem mass spectrometry (ESI MS/MS) of
      Boc-protected peptides containing repeats of L-Ala-gamma4Caa/gamma4Caa-L-Ala:
      differentiation of some positional isomeric peptides.
AB  - High-resolution electrospray ionization (ESI) quadrupole time-of-flight and ion
      trap tandem mass spectrometry has been used to distinguish the positional isomers
      of a new class of N-blocked hybrid peptides containing repeats of the amino
      acids, L-Ala-gamma(4)Caa ((l))/gamma(4)Caa((l))-L-Ala [Caa((l)) = Carbo (lyxose)
      amino acid, derived from D-mannose]. Both MS/MS and MS(3) of protonated isomeric
      peptides produce characteristic fragmentation involving the peptide backbone, Boc
      group, and the side-chain. It is interesting to observe that the abundant y(n)(+)
      ions are formed when the corresponding amide -NH does not participate in the
      helical structures in solution phase and relatively low abundance y(n)(+) ions
      resulted when the amide -NH involves in the H-bonding. Thus, it was possible to
      identify the amide -NH hydrogens that participate in the helical structures
      through H-bonding in solution phase. Further, negative ion ESI MS/MS has also
      been found to be useful for differentiating these isomeric peptide acids.

PMID- 17223354
TI  - Liquid matrix deposition on conductive hydrophobic surfaces for tuning and
      quantitation in UV-MALDI mass spectrometry.
AB  - With its highly fluctuating ion production matrix-assisted laser
      desorption/ionization (MALDI) poses many practical challenges for its application
      in mass spectrometry. Instrument tuning and quantitative ion abundance
      measurements using ion signal alone depend on a stable ion beam. Liquid MALDI
      matrices have been shown to be a promising alternative to the commonly used solid
      matrices. Their application in areas where a stable ion current is essential has
      been discussed but only limited data have been provided to demonstrate their
      practical use and advantages in the formation of stable MALDI ion beams. In this
      article we present experimental data showing high MALDI ion beam stability over
      more than two orders of magnitude at high analytical sensitivity (low femtomole
      amount prepared) for quantitative peptide abundance measurements and instrument
      tuning in a MALDI Q-TOF mass spectrometer. Samples were deposited on an
      inexpensive conductive hydrophobic surface and shrunk to droplets <10 nL in size.
      By using a sample droplet <10 nL it was possible to acquire data from a single
      irradiated spot for roughly 10,000 shots with little variation in ion signal
      intensity at a laser repetition rate of 5-20 Hz.

PMID- 17223355
TI  - Development of a MALDI-TOF-MS method to identify and quantify
      butyrylcholinesterase inhibition resulting from exposure to organophosphate and
      carbamate pesticides.
AB  - A novel, proteomics based method was developed for the detection, quantification,
      and categorization of serum butyrylcholinesterase (BChE) inhibitors, including
      organophosphates (OPs) and carbamates (CBs). This method was based on the MALDI
      TOF-MS analysis of the trypsin generated BChE active site peptide (191
      SVTLFGESAGAASVSLHLLSPR-212) previously modified by reaction with an OP or CB. The
      ionization efficiency of OP modified active site peptides by MALDI was greatly
      improved by adding diammonium citrate to the MALDI matrix, which made the
      quantification of OP exposure feasible. Excellent linearity (r2 > 0.98) between
      the normalized abundance ratios (NARs) and OP concentrations or logarithm of
      carbaryl concentration was obtained. The accuracy of the developed assay was
      evaluated by comparison of IC50 and IC100 values from the assay with those
      determined by the Ellman method. Results from this method were comparable with
      those from the Ellman method. The advantage of the assay was that both the origin
      and the extent of pesticide exposure can be determined in one analysis. Our MALDI
      method can provide critical evidence for the pesticide exposure at low BChE
      inhibition levels even down to 3%, not available with the Ellman method.

PMID- 17223356
TI  - betaIV-spectrin forms a diffusion barrier against L1CAM at the axon initial
      segment.
AB  - Axonal and somatodendritic plasma membranes of polarized neurons express distinct
      sets of functional molecules. It is known that the neuronal polarity can be
      maintained by a barrier that impedes diffusional mixing of membrane components
      between the two domains. Using betaIV-spectrin knockout mice, we demonstrate the
      involvement of this cytoskeletal protein in the formation of a barrier that
      selectively blocks lateral mobility of L1 cell adhesion molecule (L1CAM) at the
      axon initial segment of hippocampal neurons. We also show that the betaIV
      spectrin-based barrier is required for the axon-specific distribution of L1CAM
      both in vitro and in vivo. The barrier activity against L1CAM may depend on
      direct interactions of L1CAM with ankyrinG, a protein binding to betaIV-spectrin,
      rather than on steric hindrance by other transmembrane proteins clustered at the
      axon initial segment. Our results highlight the role of betaIV-spectrin and
      ankyrinG as critical components of a selective barrier against L1CAM.

PMID- 17223357
TI  - Expression, purification and biochemical characterization of a single-stranded
      DNA binding protein from Herbaspirillum seropedicae.
AB  - An open reading frame encoding a protein similar in size and sequence to the
      Escherichia coli single-stranded DNA binding protein (SSB protein) was identified
      in the Herbaspirillum seropedicae genome. This open reading frame was cloned into
      the expression plasmid pET14b. The SSB protein from H. seropedicae, named Hs_SSB,
      was overexpressed in E. coli strain BL21(DE3) and purified to homogeneity. Mass
      spectrometry data confirmed the identity of this protein. The apparent molecular
      mass of the native Hs_SSB was estimated by gel filtration, suggesting that the
      native protein is a tetramer made up of four similar subunits. The purified
      protein binds to single-stranded DNA (ssDNA) in a similar manner to other SSB
      proteins. The production of this recombinant protein in good yield opens up the
      possibility of obtaining its 3D-structure and will help further investigations
      into DNA metabolism.

PMID- 17223358
TI  - Use of dual affinity tags for expression and purification of functional
      peripheral cannabinoid receptor.
AB  - The human peripheral cannabinoid receptor (CB2) was expressed as a fusion with
      the maltose-binding protein (at the N-terminus), thioredoxin A (at the C
      terminus) and two small affinity tags (a Strep-tag and a polyhistidine tag).
      Expression levels of the recombinant receptor in Escherichia coli BL21(DE3) cells
      were dependent on location and type of tags in the expression construct, and were
      as high as 1-2mg per liter of bacterial culture. The recombinant receptor was
      ligand binding-competent, and activated cognate G-proteins in an in vitro coupled
      assay. The fusion CB2-125 protein was purified by immobilized metal affinity
      chromatography on a Ni-NTA resin. Maltose-binding protein, thioredoxin and a
      decahistidine tag were removed from the fusion by treatment with Tobacco etch
      virus (Tev) protease. Purification to over 90% homogeneity of the resulting CB2,
      containing an N-terminal Strep-tag was achieved by affinity chromatography on a
      StrepTactin resin. Circular dichroism spectroscopy indicated an alpha-helical
      content of the purified recombinant protein of approximately 54%. The expression
      and purification protocol allows for production of large (milligram) quantities
      of functional peripheral cannabinoid receptor, suitable for subsequent structural
      characterization. Preliminary results of reconstitution experiments indicate that
      the CB2 has retained its ligand-binding properties.

PMID- 17223359
TI  - Expression, purification, and characterization of arginine deiminase from
      Lactococcus lactis ssp. lactis ATCC 7962 in Escherichia coli BL21.
AB  - The arcA gene that encodes arginine deiminase (ADI, EC 3.5.3.6)--a key enzyme of
      the ADI pathway--was cloned from Lactococcus lactis ssp. lactis ATCC 7962. The
      deduced amino acid sequence of the arcA gene showed high homology with the arcA
      gene from Lactobacillus plantarum (99%) and from Lactobacillus sakei (60%),
      respectively. The arcA gene from Lc. lactis spp. lactis ATCC 7962 was expressed
      in soluble fraction of recombinant Escherichia coli BL21. ADI produced from Lc.
      lactis spp. lactis ATCC 7962 (LADI) in E. coli BL21 (DE3) was purified using
      sequential Q-Sepharose anion exchange and Sephacryl S-200 gel filtration column
      chromatography. The final yield of LADI in the purification procedure was 63.5%,
      and the specific activity was 140.27 U/mg. The presence of purified LADI was
      confirmed by N-terminal sequencing and determination of the molecular mass. The
      LADI had a molecular mass of about 140 kDa, and comprised a homotrimer of 46 kDa
      in the native condition. LADI exhibited only 35% amino acid sequence homology
      with ADI from Mycoplasma arginini. However, LADI shared a similar three
      dimensional structure. The K(M) and V(max) values for arginine were 8.67+/-0.045
      mM (mean+/-SD) and 344.83+/-1.79 micromol/min/mg, respectively, and the optimum
      temperature and pH for the production of LADI were 60 degrees C and 7.2.

PMID- 17223360
TI  - Expression, purification, and characterization of human acetyl-CoA carboxylase 2.
AB  - The full-length human acetyl-CoA carboxylase 1 (ACC1) was expressed and purified
      to homogeneity by two separate groups (Y.G. Gu, M. Weitzberg, R.F. Clark, X. Xu,
      Q. Li, T. Zhang, T.M. Hansen, G. Liu, Z. Xin, X. Wang, T. McNally, H. Camp, B.A.
      Beutel, H.I. Sham, Synthesis and structure-activity relationships of N-{3-[2-(4
      alkoxyphenoxy)thiazol-5-yl]-1-methylprop-2-ynyl}carboxy derivatives as selective
      acetyl-CoA carboxylase 2 inhibitors, J. Med. Chem. 49 (2006) 3770-3773; D. Cheng,
      C.H. Chu, L. Chen, J.N. Feder, G.A. Mintier, Y. Wu, J.W. Cook, M.R. Harpel, G.A.
      Locke, Y. An, J.K. Tamura, Expression, purification, and characterization of
      human and rat acetyl coenzyme A carboxylase (ACC) isozymes, Protein Expr. Purif.,
      in press). However, neither group was successful in expressing the full-length
      ACC2 due to issues of solubility and expression levels. The two versions of
      recombinant human ACC2 in these reports are either truncated (lacking 1-148 aa)
      or have the N-terminal 275 aa replaced with the corresponding ACC1 region (1-133
      aa). Despite the fact that ACC activity was observed in both cases, these
      constructs are not ideal because the N-terminal region of ACC2 could be important
      for the correct folding of the catalytic domains. Here, we report the high level
      expression and purification of full-length human ACC2 that lacks only the N
      terminal membrane attachment sequence (1-20 and 1-26 aa, respectively) in
      Trichoplusia ni cells. In addition, we developed a sensitive HPLC assay to
      analyze the kinetic parameters of the recombinant enzyme. The recombinant enzyme
      is a soluble protein and has a K(m) value of 2 microM for acetyl-CoA, almost 30
      fold lower than that reported for the truncated human ACC2. Our recombinant
      enzyme also has a lower K(m) value for ATP (K(m)=52 microM). Although this
      difference could be ascribed to different assay conditions, our data suggest that
      the longer human ACC2 produced in our system may have higher affinities for the
      substrates and could be more similar to the native enzyme.

PMID- 17223361
TI  - Comparison of natural and recombinant clitocypins, the fungal cysteine protease
      inhibitors.
AB  - A member of the cysteine protease inhibitor clitocypin gene family from
      basidiomycete Clitocybe nebularis was expressed in Escherichia coli. Following
      careful optimization of the expression procedure the active inhibitor was
      purified from inclusion bodies and its properties examined and compared to those
      of the natural clitocypin. The CD spectrum of recombinant clitocypin was similar
      to that of natural clitocypin, indicating that protein was properly refolded
      during purification. In spite of some differences in primary structure,
      structural, functional and immunological equivalence was established. Kinetic
      analyses of the natural and recombinant clitocypins were performed. Both
      clitocypins inhibited a range of cysteine proteases to a similar extent, and
      demonstrated an unusually broad inhibitory spectrum, including distantly related
      proteases, such as papain and legumain, belonging to different protease families.
      The homogenous, biologically active recombinant clitocypin is obtained at levels
      adequate for further structure-function studies.

PMID- 17223362
TI  - A BOLD search for baseline.
AB  - While we occasionally observe negative BOLD signals, its physiological basis has
      remained uncertain. This is in part due to the qualitative use of fMRI where the
      baseline is conveniently differenced away to reveal focal area(s) of interest.
      Recently, however, there has been a noticeable trend towards quantitative
      neuroimaging where changes in oxidative energetics (CMR(O2)) are quantified by
      calibrated fMRI. Pasley et al. [Pasley, B.N., Inglis, B.A., Freeman, R.D., 2007.
      Analysis of oxygen metabolism implies a neural origin for the negative BOLD
      response in human visual cortex. NeuroImage] used calibrated fMRI in conjunction
      with a novel stimulus paradigm to investigate the neural basis of the negative
      BOLD signal in awake humans. They hypothesized - based on prior results - that if
      the baseline was lowered then DeltaCMR(O2) would have to be larger. While their
      main findings point to an energetic basis for the negative BOLD signal, their
      results have far reaching implications for the present definition of baseline as
      well as for future research investigating the neural and/or energetic basis of
      baseline.

PMID- 17223363
TI  - Mapping the amphetamine-evoked changes in [11C]raclopride binding in living rat
      using small animal PET: modulation by MAO-inhibition.
AB  - The performance of small animal PET for neuroreceptor studies in a
      psychopharmacological challenge paradigm is not yet well-described. Therefore, we
      used microPET and [(11)C]raclopride to map the availability of dopamine D(2/3)
      receptors in brain of anesthetized rats, first in a baseline condition, and again
      after challenge with saline or d-amphetamine. Parametric maps of the specific
      binding (binding potential, pB) were calculated using a reference tissue input
      from cerebellum, and spatially normalized to a digitized stereotaxic coordinate
      system for rat brain. In volumes of interest (VOIs), the mean baseline pB (n=6)
      was 2.05 in dorsal striatum (caudate-putamen), and 1.34 in ventral striatum
      (nucleus accumbens), and did not significantly differ upon retest 2 h later. The
      availability of [(11)C]raclopride binding sites at baseline was 8% higher in the
      right striatum. Challenge with amphetamine sulfate (1 mg/kg, i.v., n=4) decreased
      pB by 19% in both ventral and dorsal striatum. We have earlier predicted that
      blockade of monoamine oxidase (MAO) should potentiate the amphetamine-evoked
      dopamine release, thus enhancing the displacement of [(11)C]raclopride binding in
      vivo. However, pretreatment of rats with pargyline hydrochloride (4 mg/kg, n=4;
      20 mg/kg, n=4) 1 day prior to PET did not potentiate the amphetamine-evoked
      reduction in dopamine receptor availability within the extended striatum. We
      conclude that small animal PET can be used to investigate stimulant-induced
      dopamine release, but that the spatial resolution is insufficient to detect
      differences between relative changes in dorsal vs. ventral divisions of the rat
      striatum. Furthermore, the present results do not reveal potentiation of the
      amphetamine-evoked release of dopamine in rats with MAO inhibition.

PMID- 17223364
TI  - Pre-training to find a hidden platform in the Morris water maze can compensate
      for a deficit to find a cued platform in a rat model of Parkinson's disease.
AB  - The bilateral intranigral infusion of 1 micromol 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP) in adult male Wistar rats caused a specific and partial
      loss of substantia nigra pars compacta (SNc) dopamine neurons, a partial
      depletion of striatal dopamine, and a deficit to learn the intra-maze cued
      version of the Morris water maze. Pre-training the SNc rats in the spatial
      version of the water maze or simply maintaining the animals on the water maze
      platform reversed this deficit. This improvement was even observed when the order
      of the extra-maze cues presented to the rats during pre-training of the spatial
      version was changed during training of the intra-maze cued version. However, this
      deficit was not reversed either by maintaining the animals on the platform if the
      spatial cues were surrounded and covered with a curtain or by swimming sessions
      in the maze without the escape platform and the curtain. These findings suggest
      that none of the following elements alone, learned during the spatial task pre
      training, could help SNc rats learn the intra-maze cued task: improvement of
      swimming skills or knowledge of the existence of the escape platform; distance
      between the platform and the border of the pool; location of a particular extra
      maze cue; relations among extra-maze cues. However, the simultaneous presence of
      the escape platform and extra-maze cues (irrespective of their relational
      configuration) during the pre-training sessions proved to be necessary for this
      improving effect to occur.

PMID- 17223365
TI  - Extinction-induced "despair" in the water maze, exploratory behavior and fear:
      effects of chronic antidepressant treatment.
AB  - In former studies, we found evidence for the hypothesis that withdrawal of
      negative reinforcement presents a major source for stress and despair.
      Specifically, the removal of a hidden platform in the water maze induced
      extinction of previously reinforced escape behavior and behavioral immobility,
      indicative of "despair", which also correlated with indices of fear. Here, we
      tested the effects of antidepressants on extinction in the water maze, and
      expected that such drugs would attenuate the rate of extinction of a conditioned
      place preference (CPP) and also any emotionally relevant behavior that is induced
      by the loss of reinforcement, such as immobility. Adult male Wistar rats were
      trained to escape onto a hidden platform for 10 days. Daily treatment with
      desipramine hydrochloride (DMI, 10mg/kg) or fluoxetine (FLX, 10 mg/kg) commenced
      1 day before the first of 11 extinction trials without the platform, administered
      48 h apart, and continued thereafter, as the rats were tested in an open field
      and elevated-plus maze. As compared to controls, DMI increased the resistance-to
      extinction of CPP, attenuated immobility, and increased wall climbing behavior.
      In the open field, DMI reduced activity levels, but was without effect on
      traditional fear parameters in the elevated-plus maze. FLX, by contrast,
      increased immobility during the extinction trials and fear in the elevated-plus
      maze. The withdrawal of reinforcement induced "despair" that was alleviated by
      the noradrenaline reuptake inhibitor DMI. The effects of the selective serotonin
      reuptake inhibitor FLX on immobility and fear may be explained in terms of its
      side effect profile.

PMID- 17223366
TI  - Objective assessment of nerve injury after greater saphenous vein stripping.
AB  - AIM: The complication of nerve injury after greater saphenous vein stripping for
      varicosity is subjective, and a method for objective evaluation has never been
      established. The aim of this study was to evaluate postoperative sensory changes
      by quantitative assessment of current perception threshold (CPT), and to clarify
      the relation between CPT and symptoms. PATIENTS AND METHODS: Between January 2003
      and August 2005, 27 limbs in 18 patients were enrolled. Quantitative sensory
      function was determined through CPT using a Neurometer (Neurotron, Inc., USA),
      with which saphenous nerve neural fiber selective minimum sensing values against
      three electrical stimuli (2000, 250, 5 Hz) were measured. CPT measurements were
      scheduled on the day before the operation, and 2-7 days, 1, 3, and 6 months after
      the operation. RESULTS: An increase in CPT value of more than 20% or decrease to
      below 50% compared to the preoperative value with at least two stimuli was
      defined as CPT abnormality. Subjective symptoms were observed in 13 limbs in the
      early postoperative period, and 10 limbs showed CPT abnormality. In 6 limbs with
      a CPT increase over 20% with all three stimuli, neurological symptoms continued
      for 6 months. CONCLUSIONS: CPT evaluation provides an objective indication of
      neurological symptoms in the lower limb following varicose vein surgery.

PMID- 17223367
TI  - Sulfate transport in Aspergillus nidulans: a novel gene encoding alternative
      sulfate transporter.
AB  - In Aspergillus nidulans sulfate is taken up by sulfate permease encoded by the sB
      gene. A unique tight auxotrophic mutant with an impaired promoter region of the
      sulfate permease gene, sB1(pr), was isolated. Three suppressor genes were cloned
      by complementation of this mutation. One of them, described here, is the astA
      gene (alternative sulfate transporter) derived from a genomic library of the
      Japanese A. nidulans IAM 2006 strain. In the reference strain of Glasgow origin
      the astA gene was found to be a pseudogene having several nucleotide deletions in
      ORF. The gene encodes a novel type of sulfate transporter which is distinct from
      other known sulfate permeases forming the SulP family. The putative ASTA protein
      belongs to an extensive and poorly characterized Dal5 allantoate permease family
      of fungal organic anion transporters. We have shown that ASTA is a physiological
      sulfate transporter. We also report cloning and characterization of the sB gene
      in this work. Both genes, sB and astA, are regulated at the transcriptional level
      by sulfur metabolite repression (SMR).

PMID- 17223368
TI  - 13C-1H HSQC experiment of probe molecules aligned in thermotropic liquid
      crystals: sensitivity and resolution enhancement in the indirect dimension.
AB  - The spectra of molecules oriented in liquid crystalline media are dominated by
      partially averaged dipolar couplings. In the 13C-1H HSQC, due to the inefficient
      hetero-nuclear dipolar decoupling in the indirect dimension, normally carried out
      by using a pi pulse, there is a considerable loss of resolution. Furthermore, in
      such strongly orienting media the 1H-1H and 13C-1H dipolar couplings leads to
      fast dephasing of transverse magnetization causing inefficient polarization
      transfer and hence the loss of sensitivity in the indirect dimension. In this
      study we have carried out 13C-1H HSQC experiment with efficient polarization
      transfer from 1H to 13C for molecules aligned in liquid crystalline media. The
      homonuclear dipolar decoupling using FFLG during the INEPT transfer delays and
      also during evolution period combined with the pi pulse heteronuclear decoupling
      in the t1 period has been applied. The studies showed a significant reduction in
      partially averaged dipolar couplings and thereby enhancement in the resolution
      and sensitivity in the indirect dimension. This has been demonstrated on
      pyridazine and pyrimidine oriented in the liquid crystal. The two closely
      resonating carbons in pyrimidine are better resolved in the present study
      compared to the earlier work [H.S. Vinay Deepak, Anu Joy, N. Suryaprakash,
      Determination of natural abundance 15N-1H and 13C-1H dipolar couplings of
      molecules in a strongly orienting media using two-dimensional inverse
      experiments, Magn. Reson. Chem. 44 (2006) 553-565].

PMID- 17223369
TI  - Minimal YopB and YopD translocator secretion by Yersinia is sufficient for Yop
      effector delivery into target cells.
AB  - Pathogenic Yersinia sp. utilise a common type III secretion system to translocate
      several anti-host Yop effectors into the cytosol of target eukaryotic cells. The
      secreted YopB and YopD translocator proteins are essential for this process,
      forming pores in biological membranes through which the effectors are thought to
      gain access to the cell interior. The non-secreted cognate chaperone, LcrH, also
      plays an important role by ensuring pre-secretory stabilisation and efficient
      secretion of YopB and YopD. This suggests that LcrH-regulated secretion of the
      translocators could be used by Yersinia to control effector translocation levels.
      We collected several LcrH mutants impaired in chaperone activity. These poorly
      bound, stabilised and/or secreted YopB and YopD in vitro. However, these mutants
      generally maintained stable substrates during a HeLa cell infection and these
      infected cells were intoxicated by translocated effectors. Surprisingly, this
      occurred in the absence of detectable YopB- and YopD-dependent pores in
      eukaryotic membranes. A functional type III translocon must therefore only
      require minuscule amounts of secreted translocator proteins. Based on these
      observations, LcrH dependent control of translocation via regulated YopB and YopD
      secretion would need to be exquisitely tight.

PMID- 17223370
TI  - The paralogous salivary anti-complement proteins IRAC I and IRAC II encoded by
      Ixodes ricinus ticks have broad and complementary inhibitory activities against
      the complement of different host species.
AB  - Several observations suggest that inhibition of the host complement alternative
      pathway by Ixodes tick saliva is crucial to achieve blood feeding. We recently
      described two paralogous anti-complement proteins called Ixodes ricinus anti
      complement (IRAC) proteins I and II co-expressed in I. ricinus salivary glands.
      Phylogenetic analyses suggested that these sequences were diversifying by a
      process of positive Darwinian selection, possibly leading to molecules with
      different biological properties. In the present study, we tested the hypothesis
      that each paralogue may have different inhibitory activities against the
      complement of different natural host species, thereby contributing to broaden the
      host range of I. ricinus ticks. IRAC I and IRAC II were tested against the
      complement of eight I. ricinus natural host species (six mammals and two birds).
      The results demonstrate that IRAC I and IRAC II have broad and complementary
      inhibition activities against the complement of different host species. This
      report is the first description of paralogous anti-complement molecules encoded
      by a pathogen with broad and complementary inhibitory activities against the
      complement of different host species.

PMID- 17223371
TI  - Accumulation of Epstein-Barr virus (EBV) BMRF1 protein EA-D during latent EBV
      activation of Burkitt's lymphoma cell line Raji.
AB  - As a new model to elucidate molecular mechanisms in Epstein-Barr virus (EBV)
      activation, we tested the tetracycline-inducible (Tet-On)/BZLF1-oriP plasmid
      system in Raji cells. Cells transfected with this Tet-On plasmid did not activate
      EBV by doxycycline and surprisingly EBV latency was disrupted with large amounts
      of BMRF1 protein (EA-D) being accumulated in the cells. Brilliant EA-D
      fluorescence was markedly condensed in small sized cells, intra-cellular
      vesicles, and extra-cellular particles. Scanning electron microscopy demonstrated
      the extra-cellular particles to be covered with a membrane. EA-D molecules of 58,
      50, 48, and 44kDa were expressed in the cells. The high (58 and 50kDa) and low
      (48 and 44kDa) EA-D molecules appeared in the early and late stages,
      respectively. Low EA-D molecules were detected mostly in EA-D positive cells
      separated into the heaviest density layer of a discontinuous Percoll gradient.
      Such molecules could be created from high EA-D molecules by protein phosphatase
      treatment. The EA-D molecules that appeared similar were detected in EBV
      activated P3HR-1 and Akata cells. Several hypotheses concerning the accumulation
      of EA-D molecules of various polymorphic forms and their
      phosphorylation/dephosphorylation in this model system are presented, with
      possible biological and clinical relevance.

PMID- 17223372
TI  - Diagnosis of Shiga toxin producing Escherichia coli infection, contribution of
      genetic amplification technique.
AB  - There has been no culture method of choice for detecting non-O157 Shiga toxin
      producing Escherichia coli strains (STEC) because of their biochemical diversity
      The aim of this study was the assessment of verotoxin gene detection (VT1/VT2)
      within STEC PCR compared with the Vero cells cytotoxicity among O157 and non-O157
      STEC serotypes. Stool cultures were performed on Tryptic Soy Broth and sorbitol
      MacConkey agar with cefixitime and tellurite supplements which were identified as
      Escherichia coli (E. coli) by BBL crystal. Further identifications were performed
      including verotoxin production assessment by Vero cells cytotoxicity assay, PCR
      for specific VT1/VT2 genotyping, and isolates were plated on blood agar and
      tested for enterohemolysis. Vero cells cytotoxicity assay revealed that 58 of E.
      coli isolates (71.6%) were STEC. In PCR, 33 (56.9%) of the 58 strains were
      positive for the VT2 gene, 24 (41.4%) were positive for the VT1 gene and one
      isolate was positive for both genes. In comparison to Vero cells cytotoxicity,
      the sensitivity, specificity of PCR were 100%. In comparative study between
      verotoxin assessment by Vero cells cytotoxicity and enterohemolytic activity,
      concordance positive results between both were 53 (91.4%). The most common
      serogroups of STEC were O157 (33%) and O26 (20%). From this study we can conclude
      that enterohemolysin production can be used as surrogate marker for STEC. The
      most rapid and promising approach for detection of STEC is by molecular method.

PMID- 17223373
TI  - Apoptosis triggered by Rv1818c, a PE family gene from Mycobacterium tuberculosis
      is regulated by mitochondrial intermediates in T cells.
AB  - Ectopic expression of the Mycobacterium tuberculosis PE-family gene Rv1818c,
      triggers apoptosis in the mammalian Jurkat T cells, which is blocked by anti
      apoptotic protein Bcl-2. Although complete overlap is not observed, a
      considerable proportion of cellular pools of ectopically expressed Rv1818c
      localizes to mitochondria. However, recombinant Rv1818c does not trigger release
      of cytochrome c from isolated mitochondria even though Rv1818c protein induced
      apoptosis of Jurkat T cells. Apoptosis induced by Rv1818c is blocked by the broad
      spectrum caspase inhibitory peptide zVAD-FMK. Unexpectedly, Rv1818c-induced
      apoptosis is not blocked in a Jurkat sub-clone deficient for caspase-8 (JI 9.2)
      or in cells where caspase-9 function is inhibited or expression of caspase-9
      reduced by siRNA, arguing against a central role for these caspases in Rv1818c
      induced apoptotic signaling. Depleting cellular pools of the mitochondrial
      protein Smac/DIABLO substantially reduces apoptosis consistent with mitochondrial
      involvement in this death pathway. We present evidence that Rv1818c-induced
      apoptosis is blocked by the co-transfection of an endogenous inhibitor of caspase
      activation, XIAP in T cells. Additionally, Rv1818c is released into extracellular
      environment via exosomes secreted by M. tuberculosis infected BM-DC's and
      macrophages. Furthermore, the extracellular Rv1818c protein can be detected in T
      cells co-cultured with infected BM-DC's. Taken together, these data suggest that
      Rv1818c-induced apoptotic signaling is likely regulated in part by the Smac
      dependent activation of caspases in T cells.

PMID- 17223374
TI  - How long should patients take medications for postmenopausal osteoporosis?
AB  - Several medications have proved effective in reducing the fracture risk in
      postmenopausal women with osteoporosis. The optimal duration of use of these
      medications remains to be established, however. Gains in bone mineral density
      (BMD) persisted throughout 10 years of treatment with alendronate or 7 years with
      risedronate. However, proof of long-term protection against fractures was
      obtained only for shorter treatment periods, 4 years with alendronate and 5 years
      with risedronate. The persistence of treatment effects after drug discontinuation
      varies across medications, and further studies are needed before this point can
      be incorporated into treatment decisions. With raloxifene, the BMD effect
      observed after 3 and 4 years persisted when the drug was given for 8 years, and
      the fracture risk reduction was similar after 4 years and after 3 years. The long
      term safety profile also was similar, with a significant decrease in the
      incidence of invasive estrogen-receptor-positive breast cancer and a persistent
      increase in the risk of deep vein thrombosis. However, a sharp drop in BMD
      occurred upon raloxifene discontinuation. Thus, 4 years may be appropriate for
      anti-resorptive drug therapy. However, the optimal treatment duration should be
      determined on a case-by-case basis according to the results of regular fracture
      risk evaluations.

PMID- 17223375
TI  - [Interest of modern imagery for conservative management of a placenta percreta].
AB  - The placenta percreta is a rare form of anomaly of placental insertion
      threatening the maternal and foetal lives. The incidence of abnormal placental
      adhesion is correlated to frequency of caesarean sections and advanced maternal
      age. Patients who are at high risk should be identified during pregnancy by
      ultrasound examination with Color Doppler looking for characteristic features.
      The practice of MRI in case of echographic suspicion may be useful, particularly
      in posterior placentas. A late diagnosis, in an emergency context, leads
      generally to hysterectomy and even to partial resection of neighbour organs.
      Thus, we report the case of a conservative management associating uterine
      embolisation following an elective caesarean delivery at 36 weeks gestation. In
      postpartum, the placental involution was followed clinically and by imagery. In
      our case, a total abdominal hysterectomy was performed on the fifth postoperative
      week because of a severe antibiotics resistant infection. No blood transfusion
      was required and the postoperative period was uneventful. This clinical case aims
      to show, through an analysis of the recent data of the literature, the interest
      of modern imagery to select patients with suspected placenta percreta that would
      be suitable candidates for conservative management.

PMID- 17223376
TI  - Ultrasonically driven continuous process for vegetable oil transesterification.
AB  - A bench scale continuous process for the manufacture of biodiesel from neat
      vegetable oils under high power low frequency ultrasonic irradiation was
      investigated. The experimental studies explored variations in alcohol-oil
      stoichiometry and type of oil. Important parameters such as residence time and
      reaction volume were considered. The highest conversion was achieved when short
      residence time was employed. The transesterification under ultrasonic irradiation
      is mainly influenced by the residence time in the reactor and alcohol-oil molar
      ratio.

PMID- 17223377
TI  - Cytotoxic, genotoxic, and mutagenic effects of diphenyl diselenide in Chinese
      hamster lung fibroblasts.
AB  - Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a
      variety of pharmacologically active organic selenium compounds, and may increase
      the risk of human exposure to this chemical at the workplace. In a previous
      study, we demonstrated the pro-oxidant action and the mutagenic properties of
      this compound on bacteria and yeast. In the present study, we evaluated the
      putative cytotoxic, pro-oxidant, genotoxic, and mutagenic properties of this
      molecule in V79 Chinese lung fibroblast cells. When cells were treated with
      increasing concentrations of DPDS, its cytotoxic activity, as determined using
      four cell viability endpoints, occurs in doses up to 50 microM. The MTT reduction
      was stimulated, which may indicate reactive oxygen species (ROS) generation.
      Accordingly, the treatment of cells for 3h with cytotoxic doses of DPDS increased
      TBARS levels, and sensitized cells to oxidative challenge, indicating a pro
      oxidant effect. The measurement of total, reduced, and oxidized glutathione
      showed that DPDS can lead to lower intracellular glutathione depletion, with no
      increase in the oxidation rate in a dose- and time-dependent manner. At the
      higher doses, DPDS generates DNA strand breaks, as observed using the comet
      assay. The treatment also induced an increase in the number of binucleated cells
      in the micronucleus test, showing mutagenic risk by this molecule at high
      concentrations. Finally, pre-incubation with N-acetylcysteine, which restored GSH
      to normal levels, annulled DPDS pro-oxidant and genotoxic effects. These findings
      show that DPDS-induced oxidative stress and toxicity are closely related to
      intracellular level of reduced glutathione. Moreover, at lower doses, this
      molecule has antioxidant properties, protecting the cell against oxidative damage
      induced by hydrogen peroxide.

PMID- 17223378
TI  - Micronucleus induction and FISH analysis in buccal cells and lymphocytes of
      nurses administering antineoplastic drugs.
AB  - A genotoxic effect for antineoplastic drugs, in particular micronucleus
      induction, has been shown in several studies. The aim of our study was to assess
      genotoxic effects in nurses administering different mixtures of antineoplastic
      drugs in an oncology hospital by evaluating the frequency of micronuclei in
      exfoliated buccal cells and blood lymphocytes by use of the standard micronucleus
      (MN) test and by identifying, by means of FISH analysis with centromeric probes,
      the mechanism of micronucleus induction (clastogenic or aneugenic). The study
      group comprised 23 nurses, 10 of whom worked in the day-care hospital and 13 in
      the ward. Twenty healthy subjects were selected as controls. Pan-centromeric FISH
      analysis was performed on lymphocytes from a selected group of nurses (12/23
      subjects) characterized by higher MN frequencies as observed by standard Giemsa
      staining. A significant increase of micronucleus frequency compared with controls
      was found in exfoliated buccal cells of both groups of nurses: day-care hospital
      nurses 0.92 versus 0.45 (p=0.034) and ward nurses 0.94 versus 0.45 (p=0.051). An
      increase, although not statistically significant, of mean MN frequency was also
      found by the MN standard test on lymphocytes of the day-care hospital nurses
      (10.9 versus 7.5; p=0.056), while no differences were found in ward nurses (8.15
      versus 7.5; p=0.56). We found that the administration of antineoplastic drugs by
      nurses in ward units induced a higher frequency of FISH MN+ (43% of subjects)
      than in the day-care hospital (20%). This was associated with the micronucleus
      size percentage. This finding could be correlated with the different compositions
      of administered mixtures of antineoplastic drugs: in ward units the mixtures
      contained drugs, such as vinorelbine, that were absent in the mixtures
      administered in the day-care hospital. Our results show genetic damage induced by
      administration of antineoplastic drugs, particularly in exfoliated buccal cells.
      This result suggests the useful application of this non-invasive sampling to
      evaluate genotoxic effects of occupational exposure to mixtures of inhalable
      chemicals at low doses.

PMID- 17223379
TI  - Utility of NBD-Cl for the spectrophotometric determination of some skeletal
      muscle relaxant and antihistaminic drugs.
AB  - A simple, accurate, precise and sensitive colorimetric method for the
      determination of some skeletal muscle relaxant drugs, namely orphenadrine citrate
      (I), baclofen (II), antihistaminic drugs as acrivastine (III) and fexofenadine
      hydrochloride (IV) is described. This method is based on the formation of charge
      transfer complex with 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) in non
      aqueous medium. The orange color products were measured at 472, 465, 475 and 469
      nm for drugs I, II, III and IV, respectively. The optimization of various
      experimental conditions was described. Beer's Law was obeyed in the range (2.5
      17.5), (5-70), (2.5-25) and (10-50)microg/ml for drugs I, II, III and IV,
      respectively. The molar absorptivity (epsilon), sandell sensitivity,
      detection((LOD)) and quantitation limits((LOQ)) are calculated. The procedure was
      favorably applied for determination of certain pharmaceutical dosage forms
      containing the studied drugs. The obtained results were compared with the
      official and reported methods. There were no significant differences between
      proposed, reported and the official methods.

PMID- 17223380
TI  - Theta EEG dynamics of the error-related negativity.
AB  - OBJECTIVE: The error-related negativity (ERN) is a response-locked brain
      potential (ERP) occurring 80-100ms following response errors. This report
      contrasts three views of the genesis of the ERN, testing the classic view that
      time-locked phasic bursts give rise to the ERN against the view that the ERN
      arises from a pure phase-resetting of ongoing theta (4-7Hz) EEG activity and the
      view that the ERN is generated - at least in part - by a phase-resetting and
      amplitude enhancement of ongoing theta EEG activity. METHODS: Time-domain ERP
      analyses were augmented with time-frequency investigations of phase-locked and
      non-phase-locked spectral power, and inter-trial phase coherence (ITPC) computed
      from individual EEG trials, examining time courses and scalp topographies.
      Simulations based on the assumptions of the classic, pure phase-resetting, and
      phase-resetting plus enhancement views, using parameters from each subject's
      empirical data, were used to contrast the time-frequency findings that could be
      expected if one or more of these hypotheses adequately modeled the data. RESULTS:
      Error responses produced larger amplitude activity than correct responses in time
      domain ERPs immediately following responses, as expected. Time-frequency analyses
      revealed that significant error-related post-response increases in total spectral
      power (phase- and non-phase-locked), phase-locked power, and ITPC were primarily
      restricted to the theta range, with this effect located over midfrontocentral
      sites, with a temporal distribution from approximately 150-200ms prior to the
      button press and persisting up to 400ms post-button press. The increase in non
      phase-locked power (total power minus phase-locked power) was larger than phase
      locked power, indicating that the bulk of the theta event-related dynamics were
      not phase-locked to response. Results of the simulations revealed a good fit for
      data simulated according to the phase-locking with amplitude enhancement
      perspective, and a poor fit for data simulated according to the classic view and
      the pure phase-resetting view. CONCLUSIONS: Error responses produce not only
      phase-locked increases in theta EEG activity, but also increases in non-phase
      locked theta, both of which share a similar topography. SIGNIFICANCE: The
      findings are thus consistent with the notion advanced by Luu et al. [Luu P,
      Tucker DM, Makeig S. Frontal midline theta and the error-related negativity;
      neurophysiological mechanisms of action regulation. Clin Neurophysiol
      2004;115:1821-35] that the ERN emerges, at least in part, from a phase-resetting
      and phase-locking of ongoing theta-band activity, in the context of a general
      increase in theta power following errors.

PMID- 17223381
TI  - Electrophysiological evaluation of motor pathways to proximal lower limb muscles:
      a combined method and reference values.
AB  - OBJECTIVE: In contrast with their important functional and clinical role, motor
      pathways to proximal muscles of lower limbs are rarely investigated in clinical
      neurophysiology. We describe a method to evaluate central and peripheral pathways
      to these muscles and report reference values. METHODS: Recording of both
      quadriceps was performed in 100 subjects. We analyzed the maximal M response
      after electrical stimulation of the femoral nerve, the patellar T reflex and the
      motor evoked potential (MEP) after transcranial magnetic stimulation. We defined
      the central motor conduction time as the difference between the MEP latency and
      the peripheral motor conduction time, estimated as the half of the T latency
      minus 0.5ms. RESULTS: The mean MEP latency is 20.6ms (SD 1.99ms), central motor
      conduction time 10.1ms (SD 1.29ms), MEP/M amplitude ratio 60.0% (SD 15.75%).
      Normal limits according to height and age are provided for each parameter and for
      interside asymmetry. CONCLUSIONS: This method to investigate the central and
      peripheral motor pathways supplying the L2-L4 myotomes is simple, painless and
      rapidly performed. The T reflex provides additional information on the proximal
      sensory pathways. SIGNIFICANCE: This method will be useful in many clinical
      conditions.

PMID- 17223382
TI  - The pattern of auditory brainstem response wave V maturation in cochlear
      implanted children.
AB  - OBJECTIVE: Maturation of acoustically evoked brainstem responses (ABR) in hearing
      children is not complete at birth but rather continues over the first two years
      of life. In particular, it has been established that the decrease in ABR wave V
      latency can be modeled as the sum of two decaying exponential functions with
      respective time-constants of 4 and 50 weeks [Eggermont, J.J., Salamy, A., 1988a.
      Maturational time-course for the ABR in preterm and full term infants. Hear Res
      33, 35-47; Eggermont, J.J., Salamy, A., 1988b. Development of ABR parameters in a
      preterm and a term born population. Ear Hear 9, 283-9]. Here, we investigated the
      maturation of electrically evoked auditory brainstem responses (EABR) in 55 deaf
      children who recovered hearing after cochlear implantation, and proposed a
      predictive model of EABR maturation depending on the onset of deafness. The
      pattern of EABR maturation over the first 2 years of cochlear implant use was
      compared with the normal pattern of ABR maturation in hearing children. METHODS:
      Changes in EABR wave V latency over the 2 years following cochlear implant
      connection were analyzed in two groups of children. The first group (n=41)
      consisted of children with early-onset of deafness (mostly congenital), and the
      second (n=14) of children who had become profoundly deaf after 1 year of age. The
      modeling of changes in EABR wave V latency with time was based on the mean values
      from each of the two groups, allowing comparison of the rates of EABR maturation
      between groups. Differences between EABRs elicited at the basal and apical ends
      of the implant electrode array were also tested. RESULTS: There was no influence
      of age at implantation on the rate of wave V latency change. The main factor for
      EABR changes was the time in sound. Indeed, significant maturation was observed
      over the first 2 years of implant use only in the group with early-onset
      deafness. In this group maturation of wave V progressed as in the ABR model of
      [Eggermont, J.J., Salamy, A., 1988a. Maturational time-course for the ABR in
      preterm and full term infants. Hear Res 33, 35-47; Eggermont, J.J., Salamy, A.,
      1988b. Development of ABR parameters in a preterm and a term born population. Ear
      Hear 9, 283-9] of normal hearing children: a sum of two decaying exponential
      functions, one showing an early rapid decrease in latency and the other a slower
      decrease. Remarkably, the time-constants fell well within the ranges described by
      Eggermont and Salamy (i.e., 3.9 and 68 weeks), consistent with the time-course of
      the neurophysiological mechanisms presumably involved in auditory pathway
      maturation during the first 2 years of life: i.e., myelination and increased
      synaptic efficacy. In contrast, relatively little change in wave V was evident in
      children with late-onset deafness. In agreement with the notion that EABR
      maturation follows an apex-to-base gradient as described for ABR, we observed
      that wave V latencies were longer for the basal than the apical end of the
      implant electrode array and remained so throughout the study period, whatever the
      time of onset of deafness. CONCLUSIONS: The findings in the early-onset of
      deafness group support the theory that auditory pathways remain "frozen" during
      the period of sensory deprivation until cochlear implant rehabilitation restores
      the normal chronology of maturational processes. In children with late-onset
      deafness, however, some maturational processes may occur before the onset of
      deafness, and thus less additional maturation is required during the first two
      years of implant use resulting in no significant EABR latency changes being
      observed in this period. The results suggest that the rehabilitation-induced
      plasticity of the auditory pathways is, in case of late auditory deprivation,
      unlikely to result in neurophysiological outcomes similar to those observed in
      children with early auditory deprivation. SIGNIFICANCE: Changes in EABR wave V
      latency over the first 2 years of cochlear implant use were found to be well
      fitted by the sum of two decaying exponential functions in children with early
      onset deafness. This is in line with the maturation of ABR wave V latency in
      normal-hearing children over the first two years of life. Further studies are
      needed to assess whether the differences observed in terms of auditory pathways
      maturation are associated with consistent differences in terms of language
      development.

PMID- 17223383
TI  - Event related brain potentials in elderly patients with recently diagnosed
      isolated systolic hypertension.
AB  - OBJECTIVE: Isolated Systolic Hypertension (ISH) is a known risk factor for
      cognitive impairment, but the time of onset of neurocognitive changes relative to
      the onset of ISH has yet to be established. The purpose of this study was to
      investigate the relationship between systolic BP values and neurocognitive
      function in the early stages of ISH. METHODS: Twenty elderly patients with
      recently (< 2 years) diagnosed ISH and 10 elderly normotensive controls underwent
      Ambulatory Blood Pressure Monitoring (ABPM) and neurocognitive assessment,
      performed using the Mini Mental State Examination (MMSE), and the recording of
      ERPs with an odd ball acoustic paradigm. RESULTS: There were no significant
      differences in MMSE scores or in the P300 latency between ISH patients and
      controls. The N2 latency was significantly higher in ISH patients vs. controls
      (p<0.0001), and showed a significant association with both clinical and
      ambulatory systolic BP and pulse pressure values in the overall study population.
      CONCLUSIONS: These findings suggest the existence of early subclinical
      alterations in neurocognitive function in early ISH, detectable through ERPs.
      SIGNIFICANCE: Our findings underscore the ISH may constitute a threat to
      neurocognitive health in the elderly.

PMID- 17223384
TI  - Antiepileptic effects of low-frequency repetitive transcranial magnetic
      stimulation by different stimulation durations and locations.
AB  - OBJECTIVE: To evaluate the antiepileptic effect of low-frequency rTMS (repetitive
      transcranial magnetic stimulation) in the patients with intractable epilepsy.
      METHODS: We enrolled 35 patients with localization-related epilepsy who had
      experienced at least one complex partial seizure or a secondarily generalized
      seizure per week on a constant antiepileptic drug regimen over an 8-week period.
      rTMS was administered using a Rapid(2) magnetic stimulator with an air-cooled
      coil at 0.5Hz for 5 consecutive days at 100% of rMT (resting motor threshold).
      Patients were divided into a focal stimulation group with a localized epileptic
      focus, or a non-focal stimulation group with a non-localized or multifocal
      epileptic focus. These two groups were then randomly subdivided into four
      subgroups depending on the total number of stimulations administered, i.e., 3000
      pulse and 1500 pulse subgroups. Weekly seizure frequencies were determined for 8
      weeks before and after rTMS. To compare the number of interictal spikes before
      and after rTMS, EEG was recorded twice before (1st day) and after rTMS (5th day).
      RESULTS: Mean weekly seizure frequency was non-significantly decreased after rTMS
      (8.4-->6.8/week, -13.9%). Longer stimulation subgroups (3000 pulses, -23.0%)
      tended to have fewer seizures than shorter stimulation subgroups (1500 pulses, 
      3.0%), without statistical significance. TMS stimulation site and structural
      brain lesions did not influence seizure outcome. However, interictal spikes
      significantly decreased (-54.9%, P=0.012) after rTMS and they totally disappeared
      in 6 patients (17.1%, 6/35). CONCLUSIONS: Low-frequency rTMS reduced interictal
      spikes, but its effect on seizure outcome was not significant. Focal stimulation
      for a longer duration tended to further reduce seizure frequency. SIGNIFICANCE:
      These findings may help clinicians to further investigate the therapeutic
      potential of the rTMS for patients with intractable epilepsy.

PMID- 17223385
TI  - Tools for the genetic analysis of Mycoplasma.
AB  - The mycoplasmas have attracted much scientific attention since they contain the
      smallest known genomes of any independently viable bacterial species. However,
      the detailed genetic analysis of these bacteria has lagged behind the well
      analyzed bacterial model organisms for a long time. This is due to the use of the
      UGA codon for tryptophan rather than as stop codon, which had often prevented the
      expression of full-length Mycoplasma proteins in heterologous hosts.
      Additionally, insufficient efficiency of homologous recombination prevented the
      targeted disruption of genes in some species such as M. pneumoniae whereas
      homologous recombination is operative in other mycoplasmas. Only recently,
      efficient screening systems for the use of transposon-based mutagenesis have been
      developed to circumvent this problem and to allow the targeted isolation of
      desired transposon insertion mutants. With the availability of several Mycoplasma
      genome sequences, artificial plasmids based on the chromosomal origin of
      replication were constructed that can now be used for complementation studies and
      for the stable introduction of foreign genetic material. In this review, we give
      an overview on recent developments in Mycoplasma genetics that facilitate the
      genetic manipulation of these interesting organisms.

PMID- 17223386
TI  - Genetic polymorphisms in alveolar macrophage response-related genes, and risk of
      silicosis and pulmonary tuberculosis in Chinese iron miners.
AB  - Alveolar macrophages (AMs) play a prominent role in influencing the development
      of lung inflammation and injury. The aim of this study is to investigate the
      roles of AMs response-related genes TNF-alpha, iNOS, and NRAMP1 (SLC11A1) in
      susceptibility to silicosis and pulmonary tuberculosis (PTB), and to analyze the
      interaction of dust exposure and genetic susceptibility to silicosis,
      interactions of TNF-alpha-308 and Natural Resistance-associated Macrophage
      Protein 1 (NRAMP1) INT4, D543N polymorphisms to PTB. Several epidemiological
      designs were used: retrospective investigations on dust exposure, case-control
      studies of 184 silicosis cases and 111 miners occupationally exposed to silica
      dust, and 1:2 matched case-control studies of 61 PTB cases and 122 PTB-free
      miners. The miners and controls were recruited from an iron mining operation in
      Anhui province, China. The polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) technique was applied to detect single nucleotide
      polymorphisms. Despite the recruitment of high dust exposure among the controls,
      silicosis patients still had significantly higher dust exposure than controls
      (242.6 +/- 98.8 vs. 217.6 +/- 100.7 mg a/m(3)). The mutation of iNOS Ser608Leu is
      associated with protection against silicosis and against severity of silicosis in
      the miners. There is a 0.47-fold (95% CI: 0.28-0.79) decrease in risk of
      silicosis for individuals with C/T, T/T genotype compared with the wild-type
      homozygous (C/C) individuals after adjustment for occupational exposure, smoking,
      and drinking. The protection effect of the iNOS polymorphism was particularly
      detected in the > or = 150 mg a/m(3) exposure group (OR: 0.44, 95% CI: 0.22
      0.91). However, no interaction of dust exposure with the iNOS polymorphism was
      observed. Furthermore, the variant NRAMP1 INT4 genotype is significantly
      associated with PTB in miners. No association of other polymorphisms (NRAMP1
      D543N, TNF-alpha-308) and susceptibility to silicosis or PTB in Chinese miners
      was found. Our data showed a 3.26-fold (95% CI: 1.47-7.23) increased risk of PTB
      for miners carrying both the NRAMP1 D543N G/G and NRAMP1 INT4 G/C+C/C genotypes.
      Additionally, in miners with TNF-alpha-308 G/G genotype, the risk of PTB
      increased 2.38-fold if they carry the NRAMP1 INT4 G/C+C/C genotype (95% CI: 1.14
      4.98). In conclusion, the C>T mutation of iNOS Ser608Leu may be an important
      protective factor to miners. On the other hand, the variant NRAMP1 INT4 may play
      a role in the development of PTB in Chinese miners. Therefore, the novel
      information can be used as guideline for further mechanistic investigations and
      for strengthening specific protection protocols for workers.

PMID- 17223387
TI  - Estimates of microbial quality and concentration of copper in distributed
      drinking water are highly dependent on sampling strategy.
AB  - The numbers of bacteria generally increase in distributed water. Often household
      pipelines or water fittings (e.g., taps) represent the most critical location for
      microbial growth in water distribution systems. According to the European Union
      drinking water directive, there should not be abnormal changes in the colony
      counts in water. We used a pilot distribution system to study the effects of
      water stagnation on drinking water microbial quality, concentration of copper and
      formation of biofilms with two commonly used pipeline materials in households;
      copper and plastic (polyethylene). Water stagnation for more than 4h
      significantly increased both the copper concentration and the number of bacteria
      in water. Heterotrophic plate counts were six times higher in PE pipes and ten
      times higher in copper pipes after 16 h of stagnation than after only 40 min
      stagnation. The increase in the heterotrophic plate counts was linear with time
      in both copper and plastic pipelines. In the distribution system, bacteria
      originated mainly from biofilms, because in laboratory tests with water, there
      was only minor growth of bacteria after 16 h stagnation. Our study indicates that
      water stagnation in the distribution system clearly affects microbial numbers and
      the concentration of copper in water, and should be considered when planning the
      sampling strategy for drinking water quality control in distribution systems.

PMID- 17223388
TI  - Ruptured sinus of Valsalva aneurysm associated with noncompaction of the
      ventricular myocardium.
AB  - Rupture of a sinus of Valsalva aneurysm is a rare, but life-threatening cardiac
      abnormality that requires surgical correction when diagnosed, and is frequently
      associated with other congenital defects, particularly with ventricular septal
      defect, aortic valve regurgitation, and bicuspid aortic valve. We present the
      case of a 21-year-old man who had a ruptured aneurysm of the noncoronary sinus
      into the right atrium, a ventricular septal defect, a persistent left superior
      vena cava and a noncompaction of the ventricular myocardium diagnosed by two
      dimensional echocardiography. Surgical repair was carried out and the patient
      made an uneventful recovery.

PMID- 17223389
TI  - Pressure pain threshold changes after repeated mechano-nociceptive stimulation of
      the trapezius muscle: possible influence of previous pain experience.
AB  - We examined the relation between repeated noxious pressure over the trapezius
      muscle and changes in pressure pain thresholds (PPTs) in a before-after trial
      design. A conditioning series of 30 mechano-nociceptive stimuli was applied
      manually with a handheld algometer probe, and PPTs were measured over 1 trapezius
      muscle (skin anaesthetized) in 27 healthy women before and after the
      intervention. With a mean stimulation rate of 0.40 Hz and a mean nociceptive
      stimulation intensity of 1.78 x Threshold, subjects were found to systematically
      react with a change in PPT, either a decrease or an increase. Normalized data,
      transformed into mean unidirectional PPT differences, showed statistically highly
      significant changes after intervention. The relative risk of reacting with
      lowered PPTs on noxious stimulation was 3.7 times higher for subjects who had not
      given birth to children than for subjects who had given birth to 1 or several
      children (P<.046). When 11 subjects were tested at a second session, a clear
      correlation of PPT reactions (r=0.527; P<.001) was found. In summary, repetitive
      mechano-nociceptive stimulation of the trapezius muscle in healthy females evokes
      moderate and temporary changes in PPT that last for at least 35 minutes after
      cessation of stimulation. PERSPECTIVE: A possible development of the response
      with transiently decreased PPTs into a model for human muscle pain is an
      intriguing possibility, since other models usually involve the introduction of
      chemical or thermal agents in the muscle, but this must await further research.

PMID- 17223390
TI  - Assessor status influences pain recall.
AB  - Anecdotal clinical reports suggest that patients report differing levels of pain,
      depending on the status within the medical hierarchy of the individual gathering
      the pain rating. This observation has clinical relevance, given the practice of
      delegating the assessment of pain to lower status clinic staff members. In this
      study, both pain and mood were assessed in 70 patients diagnosed with low back
      pain at pretreatment, immediately after epidural lumbar injection, and again 2
      weeks later by phone. At the 2-week follow-up, patients were also asked to recall
      the postprocedural rating that they had given immediately after the injection.
      This rating was obtained by either the treating physician or by a research
      assistant who was present at the time of injection, on a randomly determined
      basis. Current ratings of pain and mood did not differ for either group before
      the epidural injection, after the epidural injection, or at the 2-week follow-up.
      Two-week recall of postprocedural pain did, however, differ depending on assessor
      status. Those called by the physician provided recalled pain ratings that closely
      matched the ratings provided immediately after the procedure. Those called by the
      research assistant provided ratings that were 86% higher (that is, worse) than
      their original ratings. This status-driven bias in recalled postprocedural pain
      reporting is discussed in the context of social demands inherent in the physician
      patient relationship, with implications for assessing treatment effectiveness in
      clinical practice and research. PERSPECTIVE: Accurate assessment of patients'
      pain is critical to effective pain management and treatment planning. This study
      found evidence of a status-based bias in which physicians elicited lower ratings
      of previously experienced pain associated with treatment procedures than did
      staff members of lower status.

PMID- 17223391
TI  - Short-term variability of nitric oxide diffusing capacity and its components.
AB  - When monitoring nitric oxide diffusing capacity (DL(NO)) in patients, it is
      necessary to distinguish natural biological variation from a real change in
      alveolar-membrane conductance. The short-term variability of single-breath DL(NO)
      has not been established. The aim was to determine the short-term variability
      DL(NO) in healthy subjects. Twelve healthy subjects performed single-breath hold
      diffusing capacity tests at rest over a 2-month period (eight separate sessions
      with 8+/-3 days between each session). Each subject inhaled 41+/-4 ppm NO and a
      standard diffusion mixture. DL(NO), which is a multiple of the membrane diffusing
      capacity for carbon monoxide (Dm(CO)), as well as carbon monoxide diffusing
      capacity (DL(CO)) and pulmonary capillary blood volume (V(c)) remained unaltered
      over the 2-month period (P>0.05). Reproducibility (calculated as 2.77 multiplied
      by the within-subject standard deviation) over eight sessions was 20, 5 and 8 mL
      min(-1)mmHg(-1) for DL(NO), DL(CO) and Dm(CO), respectively, and 19 mL for V(c)
      (when Dm(CO)=DL(NO)/2.42). DL(NO), DL(CO), Dm(CO) and V(c) remain unchanged over
      a period of 2 months. Since the inter-session variability is 20, 5 and 8 mL min(
      1)mmHg(-1) for DL(NO), DL(CO) and Dm(CO), and 19 mL for V(c), a meaningful change
      should equal or exceed those values. While there is a small chance that week-to
      week variation can also be partly due to mild pathophysiological changes, any
      differences that are below the reproducibility values are likely to be natural
      biological variation or technical variation of the equipment, rather than true
      physiological change.

PMID- 17223392
TI  - Determination of clarithromycin in human serum by high-performance liquid
      chromatography after pre-column derivatization with 9-fluorenylmethyl
      chloroformate: application to a bioequivalence study.
AB  - A sensitive liquid chromatographic method for the analysis of clarithromycin, a
      macrolide antibiotic, in human serum using pre-column derivatization with 9
      fluorenylmethyl chloroformate (FMOC-Cl) is described. The method involved liquid
      liquid extraction of the drug and an internal standard (amantadine) followed by
      pre-column derivatization of the analytes with FMOC-Cl. A mixture of 0.05 M
      phosphate buffer containing triethylamine (2 mL L(-1); pH 3.8) and methanol
      (17:83, v/v) was used as mobile phase and chromatographic separation was achieved
      on a Shimpack CLC-ODS column. The eluate was monitored by a fluorescence detector
      with respective excitation and emission wavelengths of 265 and 315 nm. The
      analytical method was linear over the concentration range of 0.025-10 microg mL(
      1) of clarithromycin in human serum with a limit of quantification of 0.025
      microg mL(-1). The assay is sensitive enough to measure drug levels obtained in
      human single dose studies. In the present method, sensitivity and run time of
      analysis have been improved, and successfully applied in a bioequivalence study
      of three different clarithromycin preparations in 12 healthy volunteers.

PMID- 17223393
TI  - Ethanol analysis from biological samples by dual rail robotic autosampler.
AB  - Detection, identification, and quantitation of ethanol and other low molecular
      weight volatile compounds in liquid matrices by headspace gas chromatography
      flame ionization detection (HS-GC-FID) and headspace gas chromatography-mass
      spectrometry (HS-GC-MS) are becoming commonly used practices in forensic
      laboratories. Although it is one of the most frequently utilized procedures,
      sample preparation is usually done manually. Implementing the use of a dual-rail,
      programmable autosampler can minimize many of the manual steps in sample
      preparation. The autosampler is configured so that one rail is used for sample
      preparation and the other rail is used as a traditional autosampler for sample
      introduction into the gas chromatograph inlet. The sample preparation rail draws
      up and sequentially adds a saturated sodium chloride solution and internal
      standard (0.08%, w/v acetonitrile) to a headspace vial containing a biological
      sample, a calibrator, or a control. Then, the analytical rail moves the sample to
      the agitator for incubation, followed by sampling of the headspace for analysis.
      Using DB-624 capillary columns, the method was validated on a GC-FID and
      confirmed with a GC-MS. The analytes (ethanol, acetonitrile) and possible
      interferences (acetaldehyde, methanol, pentane, diethyl ether, acetone,
      isopropanol, methylene chloride, n-propanol, and isovaleraldehyde) were baseline
      resolved for both the GC-FID and GC-MS methods. This method demonstrated
      acceptable linearity from 0 to 1500 mg/dL. The lower limit of quantitation (LOQ)
      was determined to be 17 mg/dL and the limit of detection was 5 mg/dL.

PMID- 17223394
TI  - Isolation and characterization of antioxidant and antibacterial compound from
      mango ginger (Curcuma amada Roxb.) rhizome.
AB  - The chloroform extract of mango ginger (Curcuma amada Roxb.) rhizome was
      subjected to antioxidant activity-guided purification by repeated silica gel
      column chromatography to obtain a pure antioxidant compound. The structure was
      deduced by analyzing UV, IR, liquid chromatography-mass spectrometry (LC-MS) and
      two-dimensional heteronuclear multiple quantum coherence transfer spectroscopy
      (2D-HMQCT) NMR spectral data, and named it as "Amadannulen", a novel compound. It
      exhibited DPPH radical scavenging activity, super oxide radical scavenging
      activity, lipid peroxidation inhibitory activity and metal chelating activity.
      Amadannulen also showed antibacterial activity against both Gram-positive and
      Gram-negative bacteria tested. It also exhibited bactericidal activity against M.
      luteus, B. cereus and B. subtilis.

PMID- 17223395
TI  - Annotating the human proteome: beyond establishing a parts list.
AB  - The completion of the human genome has shifted the attention from deciphering the
      sequence to the identification and characterisation of the functional components,
      including genes. Improved gene prediction algorithms, together with the existing
      transcript and protein information, have enabled the identification of most exons
      in a genome. Availability of the 'parts list' has fostered the development of
      experimental approaches to systematically interrogate gene function on the
      genome, transcriptome and proteome level. Studying gene function at the protein
      level is vital to the understanding of how cells perform their functions as
      variations in protein isoforms and protein quantity which may underlie a change
      in phenotype can often not be deduced from sequence or transcript level genomics
      experiments alone. Recent advancements in proteomics have afforded technologies
      capable of measuring protein expression, post-translational modifications of
      these proteins, their subcellular localisation and assembly into complexes and
      pathways. Although an enormous amount of data already exists on the function of
      many human proteins, much of it is scattered over multiple resources. Public
      domain databases are therefore required to manage and collate this information
      and present it to the user community in both a human and machine readable manner.
      Of special importance here is the integration of heterogeneous data to facilitate
      the creation of resources that go beyond a mere parts list.

PMID- 17223396
TI  - How does dextran sulfate prevent heat induced aggregation of protein? The
      mechanism and its limitation as aggregation inhibitor.
AB  - The effect of dextran sulfate on protein aggregation was investigated to provide
      the clues of its biochemical mechanism. The interaction between dextran sulfate
      and BSA varied with the pH values of the solution, which led to the different
      extent of aggregation prevention by dextran sulfate. Light scattering data with
      thermal scan showed that dextran sulfate suppressed BSA aggregation at pH 5.1 and
      pH 6.2, while it had no effect at pH 7.5. Isothermal titration calorimetric
      analysis suggested that the pH dependency of the role of dextran sulfate on BSA
      aggregation would be related to the difference in the mode of BSA-dextran sulfate
      complex formation. Isothermal titration calorimetric analysis at pH 6.2 indicated
      that dextran sulfate did not bind to native BSA at this pH, but interacted with
      partially unfolded BSA. While stabilizing native form of protein by the complex
      formation has been suggested as the suitable mechanism of preventing aggregation,
      our observation of conformational changes by circular dichroism spectroscopy
      showed that strong electrostatic interaction between dextran sulfate and BSA
      rather facilitated the denaturation of BSA. Combining the data from isothermal
      titration calorimetry, circular dichroism, and dynamic light scattering, we found
      that the complex formation of the intermediate state of denatured BSA with
      dextran sulfate is a prerequisite to suppress the aggregation by preventing
      further oligomerization/aggregation process of denatured protein.

PMID- 17223397
TI  - Posterior helical pits.
AB  - Posterior helical pits are an easily overlooked finding. They are uncommon in the
      general population although they do occur as an isolated autosomal dominant
      trait. We have observed posterior helical pits as a feature in three syndromes
      only: Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome and Rubinstein
      Taybi syndrome. We suggest that posterior helical pits, when present, are an
      excellent diagnostic handle.

PMID- 17223398
TI  - A 6Mb deletion in band 2q22 due to a complex chromosome rearrangement associated
      with severe psychomotor retardation, microcephaly and distinctive dysmorphic
      facial features.
AB  - High-resolution analyses of complex chromosome rearrangements (CCR) have
      demonstrated in individuals with abnormal phenotypes that not all seemingly
      balanced CCRs based on G-banding are completely balanced at breakpoint level.
      Here we report on an apparently balanced de novo CCR involving chromosomes 2, 3
      and 5 present in a 6-month-old girl. She was referred for genetic evaluation
      because of severe psychomotor retardation, distinctive dysmorphic features and
      microcephaly. A 1Mb resolution array-CGH analysis of DNA from the patient
      revealed a deletion of about 6Mb for chromosome 2. FISH analysis showed that the
      deletion interval found in band 2q22 mapped at the translocation breakpoint, and
      that the ZFHX1B gene, which is known to be involved in the Mowat-Wilson syndrome,
      is located within the deletion interval. To our knowledge this is the first case
      of a complex chromosomal rearrangement associated with Mowat-Wilson syndrome. Our
      data illustrate the important role for high-resolution investigation of
      apparently balanced chromosome rearrangements in patients with unexplained
      psychomotor retardation and/or other clinical features, and should contribute to
      our understanding of the mechanisms involved in chromosome rearrangement.

PMID- 17223399
TI  - On sampling bones for microcracks.
AB  - This paper addresses the problem of designing experiments to measure microcrack
      density in cortical bone. Microcracks are relatively scarce in bone cross
      sections, and their size requires microscope settings having small fields of
      view. Thus, substantial time is required to count cracks in each cross-section.
      Consequently, most studies evaluate a relatively small cross-sectional area from
      each specimen, the chance of finding a crack in any given field is small, and
      there is a significant chance of not finding even one crack in the specimens
      representing a particular subject. Therefore, a statistical model for microcrack
      counting was created to develop guidelines for sampling bones for microcracks.
      Three questions were addressed. 1) What are the relationships of sample size to
      variability in microcrack density results and the probability of crackless
      specimens? 2) How can sample size be chosen a priori so as to reduce the
      probability of crackless specimens and the associated variability in the data to
      an acceptable level? 3) What are the confidence intervals for the mean density of
      microcracks measured using microscopic counting? Using a Poisson model for the
      distribution of microcracks within microscope fields the total area (mm(2)) that
      should be examined for each specimen is given by A(s)=-ln(F)/Cr.Dn, where Cr.Dn
      is the expected microcrack density for an individual sample and F is the desired
      probability (expressed as a fraction) that the individual sample will contain no
      microcracks. This equation is validated against 8 results from three different
      experiments.

PMID- 17223400
TI  - Effect of modification of hydroxyapatite/collagen composites with sodium citrate,
      phosphoserine, phosphoserine/RGD-peptide and calcium carbonate on bone
      remodelling.
AB  - This study describes the early interface reaction of cancellous bone to a
      nanocrystalline hydroxyapatite cement containing type I collagen (HA/Coll) and
      its modifications with sodium citrate (CI), calcium carbonate (CA), phosphoserine
      (P) and phosphoserine plus RGD-peptide (RGD). Cylindrical implants of HA/Coll and
      its modifications were inserted into the tibia of Wistar rats. We analysed 6
      specimens per group at days 2, 4, 7, 14 and 28. CI, P and RGD modifications
      showed improved material properties (finer microstructure and higher compressive
      strength) compared to CA and HA/Coll implants. The powder X-ray diffraction (XRD)
      showed that the addition of P and CI led to an increase of alpha-TCP peaks while
      the diffraction patterns of the non-modified cement (HA/Coll) were quite similar
      with that of natural bone. All of the implants healed without adverse reactions.
      A significantly higher number of TRAP-positive osteoclasts were observed around
      CI, RGD and P on day 7 compared to CA and HA/Coll. Around CI, P and RGD a
      significantly delayed increase of ED1-positive mononuclear cells was detected.
      The amount of direct bone contact after 28 days was significantly higher around
      CI, P and RGD compared to CA and HA/Coll implants. The addition of CI, P and RGD
      appears to enhance bone remodelling at the early stages of bone healing, leading
      to increased bone formation around HA/Coll composite cements.

PMID- 17223403
TI  - More strategies for enhancing your message.

PMID- 17223404
TI  - The role of surgery in the management of septic shock--extra-abdominal causes of
      sepsis.
AB  - Septic shock is a severe inflammatory response to one or more pathogenic micro
      organisms. When a person's immune response is excessively intense, a cascade of
      phenomena may be activated that ultimately is harmful. Appropriate management of
      septic shock may include surgical intervention to remove or neutralize the septic
      focus in an effort to treat the inflammatory response cascade. This is the first
      of two articles presenting current information on the role of surgery in the
      management of a patient with septic shock. This article describes extra-abdominal
      sources of sepsis.

PMID- 17223405
TI  - Mitral valve repair.
AB  - Diseases that affect the mitral valve include mitral regurgitation, mitral
      stenosis, rheumatic heart disease, and cardiomyopathy. The results of diagnostic
      procedures are used to identify and confirm mitral valve disease, evaluate the
      patient's anatomy, and determine the severity of the disease. After the patient
      is prepared for surgery, the surgeon performs an intraoperative transesophageal
      echocardiogram and the patient is placed on cardiopulmonary bypass. A repair
      procedure (eg, annuloplasty, slidingplasty, chordal repair/transfer/replacement,
      valve replacement) is performed depending on the patient's specific anatomical
      abnormalities.

PMID- 17223406
TI  - Improving compliance with prophylactic antibiotic administration guidelines.
AB  - To reduce the incidence of surgical site infections, preoperative prophylactic
      antibiotics should be administered within 60 minutes before the initial incision
      is made. A recent study and anecdotal observations, however, indicate that rates
      for compliance with these guidelines are low. A quality improvement project was
      undertaken at a Florida health care facility to determine if implementing changes
      in preoperative processes would increase compliance with prophylactic antibiotic
      administration guidelines. After the strategies were implemented, compliance
      rates with the national guidelines for administration of antibiotics within 60
      minutes of surgical incision increased from 75% at baseline to 95%
      postimplementation.

PMID- 17223409
TI  - Comparison of effects of high (80 mg) versus low (20 mg) dose of simvastatin on C
      reactive protein and lipoproteins in patients with angiographic evidence of
      coronary arterial narrowing.
AB  - Although previous studies have demonstrated that various "statins" decrease
      levels of high-sensitivity C-reactive protein (hs-CRP), the dose-response
      relation for lowering hs-CRP by the clinically important drug simvastatin
      compared with lipid lowering is unclear. A 16-week, randomized, double-blind
      study was performed in patients with stable coronary artery disease and high hs
      CRP levels (>3 mg/L). Subjects were randomized to placebo, 20 mg of simvastatin,
      or 80 mg of simvastatin for 12 weeks. Those currently on a statin first underwent
      a 4-week washout. Of the 107 total patients randomized, 96 completed the trial,
      and 89 were able to be evaluated for efficacy. Changes in hs-CRP differed across
      simvastatin and placebo groups (change score +1.6 vs -0.6 mg/L, p = 0.004), but
      no dose response was observed when comparing 80 with 20 mg/day (-0.6 vs -0.5
      mg/L, respectively). A strong dose response was observed for changes in total (p
      <0.01) and low-density lipoprotein (p <0.001) cholesterol. hs-CRP changes did not
      correlate with low-density lipoprotein changes. In conclusion, this randomized
      trial in patients with chronic stable coronary artery disease showed a strong
      dose response for simvastatin for total and low-density lipoprotein cholesterol
      lowering but not for hs-CRP.

PMID- 17223410
TI  - Blood omega-3 and trans fatty acids in middle-aged acute coronary syndrome
      patients.
AB  - We tested the hypothesis that lower blood omega-3 (omega-3) fatty acids (FAs)
      and/or higher trans FAs are associated with the risk of an acute coronary
      syndrome (ACS). Higher levels of omega-3 FA have been associated with decreased
      risk of sudden cardiac death. However, their association with ACS risk is
      unclear. Although higher self-reported intakes of trans FAs have been linked to
      increased coronary risk, the association between blood levels of trans FA and ACS
      risk is also unknown. We analyzed the FA composition of whole blood from 94
      subjects with ACS and 94 age-, gender-, and race-matched controls. Omega-3 and
      trans FA associations with ACS were assessed using multivariable models after
      adjusting for smoking status, alcohol use, diabetes, body mass index, serum
      lipids, and history of myocardial infarction or revascularization. Subjects' mean
      age was 47 years, 54% were men, and 80% were Caucasian. Whole blood long-chain
      omega-3 FA (eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA]) content
      was 29% lower in patients than in controls (1.7 +/- 0.9% vs 2.4 +/- 1.4%, p
      <0.001), whereas trans FA content was not different (2.1 +/- 0.7% vs 2.0 +/-
      0.9%, p = NS). The multivariable-adjusted odds for case status was 0.67 (95%
      confidence interval 0.46 to 0.98) for a 1 SD increase in blood EPA + DHA. The
      inclusion of trans FAs in the EPA + DHA model did not alter this association. In
      conclusion, low blood EPA + DHA content is an independent predictor of increased
      risk for ACS, but higher blood trans FA content is not. Blood EPA + DHA may serve
      as a new, modifiable risk factor for ACS.

PMID- 17223411
TI  - Evaluation of cardiovascular risk factors and bone mineral density in patients
      undergoing coronary angiography and relation of findings to mitral annular
      calcium.
AB  - Prevalences of mitral annular calcium (MAC), osteoporosis, and coronary artery
      disease (CAD) increase with aging and often usually coexist. Correlates of MAC
      including cardiovascular risk factors and bone mineral density (BMD) have never
      been evaluated in men and women undergoing coronary angiography. Accordingly, we
      assessed the association between cardiovascular risk factors, BMD, and MAC in
      patients undergoing coronary angiography. The study population consisted of 484
      consecutive patients (180 women, mean 60 +/- 10 years of age; 304 men, mean 60 +/
      10 years of age) who underwent coronary angiography. Complete transthoracic
      echocardiographic studies were performed in all patients. Diagnosis of MAC was
      made by M-mode and cross-sectional transthoracic echocardiography. All patients
      were referred to the nuclear medicine department to measure BMD (T score) using
      dual-energy x-ray absorptiometry. The following clinical and demographic
      parameters were recorded: age, gender, body mass index, hypertension, diabetes
      mellitus, CAD, hypercholesterolemia, and smoking status. Prevalence of MAC in our
      study population was 20%. There were no statistically significant differences
      between groups with respect to body mass index, diabetes mellitus,
      hypercholesterolemia, and presence of CAD (p >0.05 for all comparisons).
      Prevalence of hypertension and mean age were significantly higher in patients
      with MAC than in those without MAC (hypertension 74% vs 52%, p <0.001; age 68 +/-
      9 vs 58 +/- 10 years, p <0.001, respectively). Age and hypertension were found to
      be independent positive risk factors for MAC, whereas T score and age-gender
      adjusted T score were found to be negatively and independently associated with
      MAC. In conclusion, we found that MAC in patients undergoing coronary angiography
      is independently and positively associated with age and hypertension and
      negatively associated with T-score measurement of BMD.

PMID- 17223412
TI  - Repolarization duration in patients with conduction disturbances after myocardial
      infarction.
AB  - This study compared different measurements of repolarization duration in patients
      after infarction with and without conduction disturbances and evaluated the
      prognostic significance of repolarization parameters for predicting mortality in
      patients with conduction abnormalities. The study population consisted of 3,282
      patients after recent myocardial infarction. Repolarization duration was measured
      using Bazett QTc and JTc (QTc minus QRS) and Rautaharju QT and JT(RR) formulas.
      All-cause mortality was the end point of the predictive models. In 259 patients
      with conduction disturbances, 76 (2.3%) had indeterminate ventricular conduction
      disturbances, 126 (3.8%) had right bundle branch block, and 47 (1.4%) had left
      bundle branch block. Patients with left bundle branch block demonstrated
      excessive prolongation of the QTc interval, which was not observed when using the
      JT(RR) interval. There were no significant differences in repolarization duration
      by gender in patients with conduction abnormalities. Repolarization parameters
      were uniformly dichotomized at the 75th percentile (QTc interval >490 ms, JTc
      interval >360 ms, QT(RR,QRS) interval >433 ms, JT(RR) interval >359 ms) to
      determine their prognostic significance for predicting mortality. After
      adjustment for significant clinical predictors of mortality, the hazard ratios
      were 1.65 for QTc interval (p = 0.062), 1.46 for JTc interval (p = 0.168), 1.71
      for QT(RR,QRS) interval (p = 0.043), and 1.70 for JT(RR) interval (p = 0.044)(.)
      In conclusion, patients with left bundle branch block, right bundle branch block,
      or indeterminate ventricular conduction disturbances show longer repolarization
      duration than patients without these conduction disturbances, and QT(RR,QRS) and
      JT(RR) intervals reflect better than QTc repolarization duration in patients with
      conduction disturbances. QT(RR) and JT(RR) intervals significantly and
      independently predict mortality in patients after infarction with conduction
      disturbances.

PMID- 17223413
TI  - Usefulness of a complete blood count-derived risk score to predict incident
      mortality in patients with suspected cardiovascular disease.
AB  - The complete blood cell (CBC) count is an inexpensive, frequently obtained blood
      test whose information content is potentially underused. We examined the
      predictive ability of the CBC count for incident death in 29,526 consecutive
      consenting patients who underwent coronary angiography. Subjects were randomly
      assigned to training (60%) and test (40%) groups and were followed for an average
      of 4.9 years. Computed and integer risk score models for all-cause death were
      developed for 30 days and 1, 5, and 10 years using multivariable logistic
      regressions applied to CBC metrics, age, and gender. The study cohort was an
      average age of 61 years, 62% were men, and had a 3.3% annual risk of mortality.
      An integer (scalar) risk score (range 0 to 18) successfully separated patient
      cohorts into subgroups at markedly different mortality risks (<1% to >14% at 30
      days). Predictive fractions (area under risk curve) at 30 days for the CBC-only
      model and the age- and gender-adjusted CBC model were 0.76 and 0.78,
      respectively, in the training set and 0.71 and 0.75, respectively, in the test
      set (all p values <<0.001). The CBC model was markedly more informative than
      models based only on hematocrit, white blood cell count, or age and gender and
      was superior to models with all 7 traditional risk factors. In conclusion, in a
      large, prospectively assembled database, a CBC risk model had high predictive
      ability for risk of incident mortality. A total CBC score is an important new
      addition to risk prediction, and it can be easily generated by computer for
      clinical use at negligible incremental cost.

PMID- 17223414
TI  - Detection of coronary artery stenosis using 40-channel computed tomography with
      multi-segment reconstruction.
AB  - Coronary angiographic studies performed with 16-channel multidetector computer
      tomographic scanners have demonstrated accurate detection of coronary vessel
      stenosis but are limited by a significant number of non-evaluable segments. To
      date, only single-center experience with multidetector computer tomography has
      been reported. We performed a prospective, blinded study at 2 institutions to
      determine the feasibility and diagnostic accuracy of coronary angiography using
      40-channel multidetector computer tomography with multi-segment reconstruction
      for the detection of obstructive coronary artery disease (CAD). Multidetector
      computer tomographic studies were performed in 85 patients who were referred for
      invasive coronary angiography with clinically suspected CAD. Datasets were
      analyzed by blinded, independent review. Of 1,145 segments that were suitable for
      analysis as determined by angiography, 1,045 (91.3%) were evaluable on
      multidetector computer tomography. Segment-based sensitivity, specificity, and
      positive and negative predictive values for detecting > or =50% luminal stenoses
      were 86%, 97%, 75%, and 97%, respectively. The area under the receiver-operating
      characteristic curves for the detection of > or =50% angiographic stenosis by
      multidetector computer tomography was 0.94. In a patient-based analysis, the
      sensitivity, specificity, and positive and negative predictive values for
      detecting subjects with > or =1 segment with > or =50% stenosis were 98%, 93%,
      94% and 93%, respectively. In conclusion, coronary angiography using 40-channel
      multidetector computer tomography with multi-segment reconstruction accurately
      detects coronary segments and patients with obstructive CAD, with a small number
      of non-evaluable cases.

PMID- 17223415
TI  - Incidence, clinical findings, and outcome of women with left ventricular apical
      ballooning syndrome.
AB  - Left ventricular apical ballooning syndrome (LVABS) is a clinical condition that
      may mimic ST-elevation acute myocardial infarction (AMI). To assess incidence,
      clinical findings, and outcome of white women with LVABS, we reviewed 305
      consecutive women with chest pain and anterior ST-elevation AMI referred for
      potential mechanical revascularization; 36 (12%) patients met the diagnostic
      criteria for LVABS and were compared with the remaining 269 women with
      angiographic evidence of coronary artery disease (CAD). Patients with LVABS
      showed a lower incidence of diabetes mellitus (5% vs 21%, p = 0.023), a higher
      rate of antecedent stressful events (26% vs 3%, p <0.0001), and a higher heart
      rate at admission (91 +/- 20 vs 82 +/- 19, p = 0.018) than women with CAD. Urgent
      angiography showed no significant CAD in patients with LVABS and an average of
      1.6 +/- 0.7 diseased coronary arteries (>50% stenosis) in the 269 control women
      (p = 0.0001). Peak creatine kinase-MB value was lower in patients with LVABS (21
      +/- 26 mU/ml) than in women with CAD (307 +/- 302 mU/ml, p = 0.0001). The only
      independent predictors of LVABS among women with anterior AMI were peak creatine
      kinase-MB value (p = 0.0001) and the presence of an antecedent stressful event (p
      = 0.001). LV systolic function at admission was similar between women with LVABS
      and those with CAD (echocardiographic ejection fraction 35.6 +/- 8.4% vs 35.5 +/-
      8.0%, p = 0.944) but was significantly different at discharge (ejection fraction
      50.1 +/- 9.6% vs 45.2 +/- 13.5%, p = 0.021). Moreover, at 6-month follow-up,
      women with LVABS showed a better survival rate (97% vs 86%, p = 0.055) and
      freedom from major cardiac events (death, reinfarction, or rehospitalization 92%
      vs 69%, p = 0.001) than women with CAD. In conclusion, few women presenting with
      clinical features of anterior AMI have LVABS. Despite a favorable outcome, LVABS
      should be considered in the differential diagnosis of women with chest pain and
      ST-segment elevation in the precordial leads. Peak creatine kinase-MB value and
      the presence of an antecedent stressful event are strong predictors of LVABS in
      women with anterior AMI.

PMID- 17223416
TI  - Comparison of effectiveness of enoxaparin versus unfractionated heparin to reduce
      silent and clinically apparent acute myocardial infarction in patients presenting
      with non-ST-segment elevation acute coronary syndrome.
AB  - Electrocardiographic (ECG) estimates of myocardial infarct size based on the
      Selvester ECG score have been shown to predict mortality and left ventricular
      function after acute myocardial infarction (AMI). This score has also been used
      to identify not clinically apparent AMI ("silent" AMI) and to determine treatment
      effect, suggesting it could serve as a clinical trial end point. The objective of
      this study was to compare the rate of silent AMI as measured by the Selvester QRS
      score in patients with a non-ST-segment elevation acute coronary syndrome treated
      with enoxaparin versus intravenous unfractionated heparin who were participating
      in a continuous ECG monitoring substudy of the Efficacy and Safety of
      Subcutaneous Enoxaparin in Non-Q-wave Coronary Events study (ESSENCE) and
      INTegrelin and Enoxaparin Randomized Assessment of acute Coronary syndrome
      Treatment trial (INTERACT). Enoxaparin was associated with a 56% relative risk
      decrease in silent AMI at 96 hours compared with unfractionated heparin (2.7% vs
      6.1% p = 0.03). Similarly, enoxaparin decreased Holter-detected myocardial
      ischemia compared with unfractionated heparin (18.7% vs 35.9%, p = 0.03). In
      conclusion, enoxaparin significantly decreased the composite of silent AMI or
      clinical AMI and death at 1 year (9.3% vs 21%, p = 0.0001).

PMID- 17223417
TI  - Risk-adjusted mortality analysis of percutaneous coronary interventions by
      American College of Cardiology/American Heart Association guidelines
      recommendations.
AB  - An American College of Cardiology (ACC)/American Heart Association (AHA) task
      force on practice guidelines in 2001 published evidence-based recommendations for
      performing percutaneous coronary interventions (PCIs). These guidelines grouped
      the indications for PCI into 4 classes (I, IIa, IIb, and III) based on analyses
      of risks and benefits. In a previous study, we found that clinical success and in
      hospital adverse events varied by indications class. However, no adjustment for
      risk was used in those comparisons. The ACC/National Cardiovascular Data Registry
      (ACC-NCDR) previously developed a risk-adjustment model for the adverse event of
      in-hospital PCI mortality. We investigated how the 14 individual risk factors in
      the ACC-NCDR PCI mortality model might differ across the 4 indications classes
      and whether estimated mortality for each class approximated the observed
      mortality for that class. We analyzed the ACC-NCDR PCI database for January 1,
      2001 to December 31, 2004. We excluded procedures performed for treatment of
      acute ST-segment elevation myocardial infarction; all others were included,
      yielding 559,273 procedures for analysis. An algorithm derived from the 2001
      guidelines was used to assign procedures to an indications class. Increasing
      frequencies of risk components were observed across classes I, IIa, IIb, and III.
      Expected mortalities for each class calculated by the risk-adjustment model were
      close to observed values (expected 0.52%, 0.59%, 1.72%, and 1.96%, respectively;
      observed 0.49%, 0.63%, 1.88%, and 1.60%, respectively). In conclusion, the ACC
      NCDR risk-adjusted mortality model can be linked to the ACC/AHA PCI guidelines,
      and together these produce mortality risk estimates by indications classes that
      are close to actual observed values. With further refinement, these methods
      should be able to be used as powerful analytic tools for quality assurance and
      appropriateness purposes.

PMID- 17223418
TI  - Predictors and outcomes of emergency department visits within 30 days following
      percutaneous coronary intervention.
AB  - Our objective was to determine the frequency and predictive factors for cardiac
      related emergency department (ED) encounters within 30 days after percutaneous
      coronary intervention (PCI). The data source was an electronic database of 2,731
      patients who had PCI from 2002 to 2004. Almost all underwent stent placement.
      Risk factors for returning to the ED were identified from clinical, anatomic, and
      demographic candidate variables using multivariate logistic regression.
      Approximately 9% of the cohort (255 of 2,731 patients) returned to the ED for
      cardiac reasons within 30 days, peaking around 3 days. ED visits were more likely
      in those whose index PCI was emergent or urgent (odds ratio [OR] 2.0, 95%
      confidence interval [CI] 1.3 to 3.0), in women (OR 1.9, 95% CI 1.5 to 2.5), and
      in those who had previous encounters with the ED or hospital (OR 1.7, 95% CI 1.5
      to 2.0). Patients receiving stents were somewhat less likely to return (OR 0.7,
      95% CI 0.5 to 1.0). In conclusion, the clinical courses of the 255 returning
      patients were generally benign, but 12% had a subsequent myocardial infarction or
      repeat PCI within 30 days of the ED encounter.

PMID- 17223419
TI  - Usefulness of routine unfractionated heparin infusion following primary
      percutaneous coronary intervention for acute myocardial infarction in patients
      not receiving glycoprotein IIb/IIIa inhibitors.
AB  - We evaluated the utility of a routine postprocedure course of unfractionated
      heparin after primary percutaneous coronary intervention (PCI) for acute
      myocardial infarction (AMI) in patients not receiving glycoprotein IIb/IIIa
      inhibitors. In the CADILLAC study, 2,082 patients with AMI who underwent primary
      PCI were randomized to receive stents versus percutaneous transluminal coronary
      angioplasty (PTCA), each with or without abciximab. In a subset of 976 patients
      who did not receive abciximab, we compared outcomes of patients who received
      postprocedural heparin (n = 758; 78%; median duration 2 days) with those who did
      not. In 421 patients treated with PTCA, postprocedural heparin use was associated
      with lower in-hospital major adverse cardiac events (MACEs; 5.3% vs 11.4%, p =
      0.069), 1-year MACEs (22% vs 31%, p = 0.08), and decreased in-hospital
      moderate/severe bleeding (2.3% vs 8.9%, p = 0.01). By multivariate analyses,
      heparin use correlated with freedom from in-hospital and 1-year MACEs in patients
      after PTCA. In contrast, in 555 patients who underwent stenting, postprocedural
      heparin use was associated with increased bleeding and hospitalization costs
      without a decrease in early or late MACEs. In conclusion, in patients with AMI
      treated with coronary stenting without glycoprotein IIb/IIIa inhibitors, routine
      postprocedural heparin was not associated with any significant benefits and may
      be safely omitted. However, in a subset of patients treated with PTCA,
      postprocedural heparin use was independently associated with fewer in-hospital
      and 1-year MACEs.

PMID- 17223420
TI  - The evolving pattern of symptomatic coronary artery disease in the United States
      and Canada: baseline characteristics of the Clinical Outcomes Utilizing
      Revascularization and Aggressive DruG Evaluation (COURAGE) trial.
AB  - Major improvements in medical therapy and percutaneous coronary intervention for
      coronary artery disease (CAD) have emerged during the previous 2 decades, but no
      randomized trial in patients with stable CAD has been powered to compare these 2
      strategies for the hard clinical end points of death or myocardial infarction
      (MI), and previous studies have not evaluated the effect of coronary stents and
      intensive medical therapy on cardiac events during long-term follow-up. Between
      1999 and 2004, 2,287 patients with documented myocardial ischemia and
      angiographically confirmed CAD were randomized to the Clinical Outcomes Utilizing
      Revascularization and Aggressive DruG Evaluation (COURAGE) trial, with a
      principal hypothesis that a strategy of percutaneous coronary intervention plus
      intensive, guideline-driven medical therapy would be superior to a strategy of
      intensive medical therapy alone. The primary end point was a composite of all
      cause mortality or acute MI (time to first event) during a 2.5- to 7-year (median
      5) follow-up. Baseline characteristics were a mean age of 62 +/- 5 years, 85%
      men, and 86% Caucasian. Mean duration of angina before randomization was 26
      months (average 10 episodes/week), and 29% of patients were smokers, 67% had
      hypertension, 38% had previous MI, 71% had dyslipidemia, 34% had diabetes, 27%
      had previous revascularization, and 69% had multivessel CAD. Approximately 55% of
      patients met established criteria for the metabolic syndrome. In conclusion,
      baseline characteristics of the COURAGE trial study population indicate a highly
      symptomatic group of patients with CAD who have a significant duration and
      frequency of antecedent angina pectoris and a high prevalence of cardiac risk
      factors.

PMID- 17223421
TI  - Statin therapy in acute coronary syndrome.

PMID- 17223422
TI  - Reduction in predicted coronary heart disease risk after substantial weight
      reduction after bariatric surgery.
AB  - In recent years, bariatric surgery has become an increasingly used therapeutic
      option for morbid obesity. The effect of weight loss after bariatric surgery on
      the predicted risk of coronary heart disease (CHD) has not previously been
      studied. We evaluated baseline (preoperative) and follow-up (postoperative) body
      mass index, CHD risk factors, and Framingham risk scores (FRSs) for 109
      consecutive patients with morbid obesity who lost weight after laparoscopic Roux
      en-Y gastric bypass surgery. Charts were abstracted using a case-report form by a
      reviewer blinded to the FRS results. The study included 82 women (75%) and 27 men
      (25%) (mean age 46 +/- 10 years). Mean body mass index values at baseline and
      follow-up were 49 +/- 8 and 36 +/- 8 kg/m(2), respectively (p <0.0001). During an
      average follow-up of 17 months, diabetes, hypertension, and dyslipidemia resolved
      or improved after weight loss. Thus, the risks of CHD as predicted by FRS
      decreased by 39% in men and 25% in women. The predicted 10-year CHD risks at
      baseline and follow-up were 6 +/- 5% and 4 +/- 3%, respectively (p < or =0.0001).
      For those without CHD, men compared favorably with the age-matched general
      population, with a final 10-year risk of 5 +/- 4% versus an expected risk of 11
      +/- 6% (p <0.0001). Likewise, women achieved a level below the age-adjusted
      expected 10-year risk of the general population, with a final risk of 3 +/- 3%
      versus 6 +/- 4% (p <0.0001). In conclusion, weight loss results in a significant
      decrease in FRS 10-year predicted CHD risk. Bariatric surgery decreases CHD risk
      to rates lower than the age- and gender-adjusted estimates for the general
      population. These data suggest substantial and sustained weight loss after
      bariatric surgery may be a powerful intervention to decrease future rates of
      myocardial infarction and death in the morbidly obese.

PMID- 17223423
TI  - Coronary artery calcium versus intima-media thickness as a measure of
      cardiovascular disease among asymptomatic adults (from the Rancho Bernardo
      Study).
AB  - Detection and quantification of subclinical coronary heart disease by noninvasive
      imaging techniques offers the potential for earlier diagnosis with targeted
      prevention and therapy. This study, designed to determine the extent to which
      carotid artery intima-media thickness (IMT) predicts coronary artery calcium
      (CAC) in asymptomatic older adults, included 141 men and 137 women > or =55 years
      of age with no previous coronary heart disease who had B-mode ultrasound of the
      common and/or internal carotid arteries in 1997 to 1999 to measure IMT and
      electron beam computed tomographic scanning in 2001 to 2002 to measure CAC score.
      Overall, 29% of participants had a severe plaque burden (CAC score >400); 50% of
      these had a CAC score >800. IMT of the common and internal carotid arteries was
      significantly associated with the CAC score measured an average of 3 years later.
      The ability to correctly identify subjects with a severe CAC score (sensitivity)
      was 50% to 60% for an IMT of the internal or common carotid artery > 80th
      percentile (internal carotid IMT > or =1.9 mm and common carotid IMT > or =1.04
      mm). Specificity, the ability to correctly identify those who did not have a
      severe CAC score (> or =400), was approximately 75%. In conclusion, IMT of the
      carotid arteries predicted the severity of CAC burden an average of 3 years later
      in community-dwelling asymptomatic older adults.

PMID- 17223424
TI  - Long-term survival of patients with heart failure and ventricular conduction
      delay treated with cardiac resynchronization therapy.
AB  - This multicenter longitudinal observational trial was designed to analyze the
      long-term outcome of patients with heart failure (HF) treated with cardiac
      resynchronization therapy (CRT) alone or with implantable cardioverter
      defibrillator (ICD) backup in a daily practice scenario. It is unknown whether
      the magnitude of survival benefits conferred by CRT in a daily practice scenario
      is comparable to what has been observed in randomized controlled trials and
      whether this benefit is sustained over the long term. The outcome of 1,303
      consecutive patients with ischemic or nonischemic cardiomyopathy on optimal
      pharmacologic therapy treated from August 1, 1995 to August 1, 2004 at 4 European
      centers with CRT alone (44%) or with ICD backup for symptomatic HF and prolonged
      QRS duration was assessed. Cumulative event-free survival was evaluated for a
      combined end point, defined as death from any cause, urgent transplantation, or
      implantation of a left ventricular assist device. The cumulative incidence of
      competing events, HF, sudden cardiac death, and noncardiac death, was also
      assessed. Event-free survival was similar across the different centers. At 1 and
      5 years, cumulative event-free survivals were 92% (95% confidence interval [CI]
      91 to 94) and 56% (95% CI 48 to 64), respectively. The cumulative incidence of HF
      deaths was 25.1% (95% CI 19 to 31.7), whereas that of sudden death was 9.5% (95%
      CI 5.1 to 15.7). Using multivariate analysis, CRT with an ICD backup was
      associated with a nonsignificant decrease in mortality by 20% (hazard ratio 0.83,
      95% CI 0.58 to 1.17, p = 0.284), with a highly significant protective effect
      against sudden cardiac death (hazard ratio 0.04, 95% CI 0.04 to 0.28, p <0.002).
      In conclusion, patients with advanced HF and a wide QRS complex routinely treated
      with CRT have a favorable long-term outcome that was reproducible at different
      centers. The leading cause of death in these patients remained HF, and this mode
      of death was competing with other causes in determining outcome. Total mortality
      was 20% lower with ICD backup (95% CI 42% lower to 17% higher) due to a
      protective effect against sudden cardiac death.

PMID- 17223425
TI  - Relation of left ventricular lead placement in cardiac resynchronization therapy
      to left ventricular reverse remodeling and to diastolic dyssynchrony.
AB  - The effects of left ventricular (LV) lead placement for cardiac resynchronization
      therapy (CRT) on LV remodeling and dyssynchrony are not well defined. Sixty-one
      patients (age 60 +/- 11 years, 76% men) were evaluated by echocardiography before
      and 4 +/- 2 months after CRT and grouped by the LV lead placement (lateral,
      posterolateral, or anterolateral). Echocardiographic measurements included LV
      volumes and LV ejection fraction. Tissue Doppler imaging was used to assess for
      inter- and intraventricular systolic and diastolic dyssynchrony. Analysis of
      variance was used to determine the effect of the LV lead placement on
      echocardiographic variables after CRT. The LV lead was placed in a lateral
      cardiac vein in 33 patients (54%), posterolateral in 15 (25%), and anterior in 13
      (21%). Lateral LV lead placement was associated with significantly smaller LV
      volumes compared with the posterolateral lead placement (p <0.01). Diastolic
      dyssynchrony improved significantly with lateral lead placement compared with the
      anterior lead location (p <0.05). Improvement in LV ejection fraction and inter-
      and intraventricular systolic dyssynchrony was similar among the 3 groups. In
      conclusion, in patients undergoing CRT, a lateral lead location resulted in
      greater reverse LV remodeling and improved diastolic dyssynchrony compared with
      other lead placement locations.

PMID- 17223426
TI  - Usefulness of preimplantation B-type natriuretic peptide level for predicting
      response to cardiac resynchronization therapy.
AB  - Nearly 1/3 of patients with heart failure (HF) fail to respond to cardiac
      resynchronization therapy (CRT). The purpose of this study was to evaluate the
      value of preimplantation brain natriuretic peptide (BNP) in predicting the
      clinical response to CRT. We retrospectively analyzed 164 patients who underwent
      CRT. Patients with New York Heart Association functional class III or IV HF
      symptoms despite maximal medical therapy, who were not on inotropic medications,
      had left ventricular ejection fraction < or =35%, and QRS duration >130 ms were
      included in the study. CRT response in patients who survived at 6-month follow-up
      was defined as no HF hospitalization and improvement of > or =1 grades in the New
      York Heart Association classification. BNP assays were performed before
      implantation and at 6-month follow-up. Patients had ischemic (47%) or nonischemic
      (53%) cardiopathy. Responders (n = 107) and nonresponders (n = 57) had similar
      baseline characteristics. Cardiac death and hospitalization for HF occurred in 5
      (4.7%) and 18 (31.6%) patients, respectively. CRT responders compared with
      nonresponders exhibited higher preimplantation BNP levels (800 +/- 823 vs 335 +/-
      348 pg/ml, p = 0.0002) and a significant reduction in the QRS duration after
      implantation (-6 +/- 34 vs +7 +/- 32 ms, p = 0.048). The preimplantation BNP was
      the only independent predictor of the CRT response (p = 0.001). A BNP value > or
      =447 pg/ml demonstrated a sensitivity of 62% and specificity of 79% in
      identifying CRT response. In a subgroup of 41 patients who underwent Doppler
      tissue imaging analysis, the preimplantation BNP was higher in patients
      presenting with intraventricular dyssynchrony (845 +/- 779 vs 248 +/- 290 pg/ml,
      p = 0.04). In conclusion, the preimplantation BNP value independently predicts
      CRT response and was superior to QRS duration reduction in identifying CRT
      responders.

PMID- 17223427
TI  - Comparison of multidetector computed tomography and two-dimensional transthoracic
      echocardiography for left ventricular assessment in patients with heart failure.
AB  - Along with coronary evaluation, 64-slice multidetector computed tomography (MDCT)
      permits comprehensive assessment of left ventricular (LV) anatomy and function;
      however, how it compares with 2-dimensional transthoracic echocardiography (TTE)
      in patients with heart failure (HF) is not known. In this study, we compared 25
      patients with ejection fractions of <45% who underwent TTE and MDCT. The global
      ejection fraction by TTE versus MDCT was 36 +/- 8% versus 38 +/- 12% (r = 0.67, p
      = NS). The mean LV end-diastolic and end-systolic diameters by TTE and MDCT were
      56 +/- 8 and 46 +/- 9 mm and 58 +/- 12 and 47 +/- 11 mm, respectively (r = 0.71
      and 0.77, respectively, both p >0.20). The mean lateral and septal wall
      thicknesses by TTE and MDCT were 10 +/- 1.4 and 11 +/- 1.5 mm and 10 +/- 1.3 and
      10 +/- 1.4 mm (r = 0.77 and 0.76, respectively, both p >0.20). The mean LV end
      diastolic and end-systolic volumes and stroke volume by TTE and MDCT were 123 +/-
      45, 78 +/- 31, and 44 +/- 21 ml and 140 +/- 58, 92 +/- 43, and 48 +/- 24 ml,
      respectively (r = 0.62, 0.67, and 0.60, respectively, all p >0.20). The regional
      wall motion assessment correlation was good between the 2 modalities (kappa =
      0.61). The interobserver correlation between the 2 MDCT readers ranged from good
      (r = 0.72 for LV end-diastolic volume) to excellent (r = 0.84 for septal wall
      thickness). In conclusion, MDCT provides comparable results to TTE for LV
      structure and functional assessment among patients with HF.

PMID- 17223428
TI  - Relation of beta(2)-adrenoceptor haplotype to risk of death and heart
      transplantation in patients with heart failure.
AB  - Heart failure (HF) is characterized by neurohormonal activation of the
      sympathetic nervous and renin-angiotensin systems. Genetic polymorphisms in these
      systems could alter the prognosis in HF. We hypothesized the genetic
      polymorphisms in the sympathetic nervous and renin-angiotensin systems are
      associated with adverse outcomes, defined as death or heart transplantation in
      patients with HF. A total of 227 patients with HF were enrolled from a tertiary
      care clinic and followed for outcomes for < or =4 years. Eight polymorphisms in 6
      genes were genotyped: beta(1)-adrenergic receptor (ADRB1, S49G, R389G), beta(2)
      adrenergic receptor (ADRB2, G16R, Q27E), alpha(2c)-adrenergic receptor (ADRA2C,
      insertion/deletion 322-325), angiotensinogen (AGT, M235T), angiotensin receptor
      type 1 (AGTR1, 1166A>C), and angiotensin-converting enzyme (ACE,
      insertion/deletion in intron 16). Most patients were treated according to
      consensus guidelines. Male gender (hazard ratio 2.24, 95% confidence interval
      1.27 to 3.94), higher New York Heart Association functional class (hazard ratio
      2.54, 95% confidence interval 1.84 to 3.52), and 2 copies of ADRB2 Arg16Gln27
      haplotype (hazard ratio 1.91, 95% confidence interval 1.09 to 3.36) increased the
      risk of adverse outcomes. In contrast, a higher serum sodium level (hazard ratio
      0.91, 95% confidence interval 0.86 to 0.97) and higher creatinine clearance
      (hazard ratio 0.99, 95% confidence interval 0.98 to 0.99) decreased the risk of
      adverse outcomes. None of the other genotypes/haplotypes were associated with
      adverse outcomes. In conclusion, ADRB2 Arg16Gln27 haplotype may significantly
      increase the risk of adverse outcomes in patients with HF receiving contemporary
      HF pharmacotherapy.

PMID- 17223429
TI  - Financial implications of a model heart failure disease management program for
      providers, hospital, healthcare systems, and payer perspectives.
AB  - Although heart failure disease management (HFDM) programs improve patient
      outcomes, the implementation of these programs has been limited because of
      financial barriers. We undertook the present study to understand the economic
      incentives and disincentives for adoption of disease management strategies from
      the perspectives of a physician (group), a hospital, an integrated health system,
      and a third-party payer. Using the combined results of a group of randomized
      controlled trials and a set of financial assumptions from a single academic
      medical center, a financial model was developed to compute the expected costs
      before and after the implementation of a HFDM program by 3 provider types
      (physicians, hospitals, and health systems), as well as the costs incurred from a
      payer perspective. The base-case model showed that implementation of HFDM results
      in a net financial loss to all potential providers of HFDM. Implementation of
      HFDM as described in our base-case analysis would create a net loss of US dollars
      179,549 in the first year for a physician practice, US dollars 464,132 for an
      integrated health system, and US dollars 652,643 in the first year for a
      hospital. Third-party payers would be able to save US dollars 713,661 annually
      for the care of 350 patients with heart failure in a HFDM program. In conclusion,
      although HFDM programs may provide patients with improved clinical outcomes and
      decreased hospitalizations that save third-party payers money, limited financial
      incentives are currently in place for healthcare providers and hospitals to
      initiate these programs.

PMID- 17223430
TI  - Significance of asymmetric basal posterior wall thinning in patients with cardiac
      Fabry's disease.
AB  - Although classic Fabry's disease results in multiple causes of death, the cardiac
      variant of Fabry's disease affects only the cardiac system and results in initial
      symmetric left ventricular (LV) hypertrophy and later LV dysfunction, asymmetric
      basal posterior LV wall thinning, restrictive mitral flow, and functional mitral
      regurgitation with end-stage chronic heart failure (CHF), leading to death. The
      purpose of this study was to investigate whether these findings predict prognoses
      in patients with cardiac Fabry's disease. In 13 consecutive men with cardiac
      Fabry's disease, LV wall thickness, the ejection fraction, mitral E-wave
      deceleration time, the LV Tei index, and functional mitral regurgitation were
      measured by echocardiography. Patients were followed for 5 to 96 months (mean 41
      +/- 9). Eight patients developed New York Heart Association class III CHF, and 6
      experienced cardiac death. A LV Tei index >0.60 and basal posterior LV wall
      thinning with a ratio of ventricular septal to posterior wall thickness >1.3
      significantly preceded CHF and death (Tei index: 4.4 and 5.1 years; posterior
      wall thinning: 4.0 and 4.7 years), respectively (p <0.05). In conclusion, an
      increased LV Tei index and asymmetric basal posterior LV wall thinning are
      important echocardiographic findings that precede CHF and cardiac death in
      patients with cardiac Fabry's disease.

PMID- 17223431
TI  - Cardiac involvement in adults with m.3243A>G MELAS gene mutation.
AB  - Cardiac data in adults with mitochondrial encephalomyopathy, lactic acidosis, and
      strokelike episodes (MELAS syndrome) or asymptomatic gene carriers with the
      mitochondrial deoxyribonucleic acid adenine-to-guanine point mutation at
      nucleotide pair 3243 are scarce. Twelve subjects (mean age 35 +/- 13 years), 8
      with MELAS syndrome (patients) and 4 asymptomatic gene carriers (carriers), were
      enrolled in the study. Each subject underwent electrocardiography, exercise
      testing, Holter monitoring, echocardiography, and genetic and biochemical
      analysis for respiratory chain enzyme activity (complex I rest activity) in
      skeletal muscle. On electrocardiography and Holter monitoring, none of the
      subjects had evidence of preexcitation, cardiac arrhythmias, or conduction
      abnormalities. Patients had significantly lower (42 +/- 17% from normal vs 103 +/
      14%, p <0.02) exercise tolerance. All but 1 of the patients and none of the gene
      carriers had ragged red fibers on muscle biopsy. The mean percentage of gene
      mutation in skeletal muscle tended to be higher in patients (53 +/- 19%, range
      19% to 73%) compared with carriers (33 +/- 20%, range 15% to 62%). Mean complex I
      rest activity in patients (36 +/- 18%, range 10% to 58%) was significantly (p
      <0.01) lower compared with carriers (120 +/- 60%, range 72% to 205%). Left
      ventricular (LV) abnormalities were confined to patients with MELAS syndrome. Two
      patients had LV hypertrophy, 5 had LV systolic abnormalities, and 5 had LV
      diastolic dysfunction. Apart from 1 patient with an isolated LV diastolic
      abnormality, all patients with LV abnormalities had ragged red fibers. Patients
      with abnormal systolic LV function had a trend toward a higher percentage of
      mutated skeletal muscle (59.7 +/- 10.7% vs 35.8 +/- 21.3%, p <0.10) and
      significantly lower complex I rest activity (26.7 +/- 14.0% vs 97.8% +/- 57.9, p
      <0.01). In conclusion, none of the MELAS gene carriers had cardiac abnormalities,
      whereas most patients with the MELAS phenotype, particularly those with ragged
      red fibers, had LV involvement.

PMID- 17223432
TI  - Comparison of diagnostic and therapeutic value of transesophageal
      echocardiography, intravascular ultrasonic imaging, and intraluminal phased-array
      imaging in aortic dissection with tear in the descending thoracic aorta (type B).
AB  - Transesophageal echocardiography (TEE) and conventional intravascular ultrasound
      (IVUS) have limited capabilities in type B aortic dissection. To evaluate its
      diagnostic value, intraluminal phased-array imaging (IPAI) was compared with IVUS
      and TEE. In 23 patients with type B aortic dissection, IPAI was tested with
      respect to its ability to depict true lumen (TL) and false lumen (FL), to
      localize which abdominal arteries originate from the TL and FL, and to identify
      all entries and reentries. After the completion of TEE, 2 additional examiners
      performed angiography and positioned an AcuNav catheter inside the TL. An IVUS
      catheter was then introduced into the TL by a fourth examiner. All examiners were
      blinded to one another. Four additional patients with type B aortic dissection
      developed peripheral malperfusion due to TL collapse. Transvenous IPAI was used
      to guide emergency fenestration of the intimal flap. TL and FL could be equally
      well identified by all diagnostic methods. IPAI detected more entries than IVUS
      (3.0 +/- 1.2 vs 0.8 +/- 0.5, p <0.001), and thoracic IPAI depicted more entries
      than TEE (1.8 +/- 1.0 vs 1.2 +/- 0.5, p <0.001). IPAI and IVUS showed >90% of the
      abdominal side branches. In all patients with peripheral malperfusion, successful
      emergency intimal flap fenestration was safely guided by IPAI. In conclusion, in
      the detailed diagnostic evaluation of type B aortic dissection, IPAI is superior
      to IVUS and TEE in detecting communications between the TL and FL. IPAI is also
      highly useful as a guiding tool for emergency intimal flap fenestration.

PMID- 17223433
TI  - Usefulness of ultrasound contrast agent to improve image quality during real-time
      three-dimensional stress echocardiography.
AB  - Dobutamine stress echocardiography is an accepted tool for the diagnosis of
      coronary artery disease. Some investigators have claimed that 3-dimensional
      imaging improves the diagnostic accuracy of dobutamine stress echocardiography.
      The purpose of the present investigation was to examine the role of contrast
      echocardiography in the improvement of segmental quality and interobserver
      agreement during stress real-time 3-dimensional echocardiography (RT3DE). The
      study comprised 36 consecutive patients with stable chest pain referred for
      routine stress testing. Three-dimensional images were acquired with an RT3DE
      system with an X4 matrix-array transducer. All available reconstructed 2
      dimensional segments were graded as optimal, good, moderate, or poor. Wall motion
      was scored as normal, mild hypokinesia, severe hypokinesia, akinesia, or
      dyskinesia. At peak stress, 466 of the 612 segments (76%) could be analyzed
      during conventional RT3DE. With contrast-enhanced RT3DE, the number of available
      segments increased to 553 (90%). The image quality index during conventional
      RT3DE was 2.2, whereas with contrast-enhanced RT3DE, it was 3.1. With
      conventional RT3DE, 2 independent observers agreed on the diagnosis of myocardial
      ischemia in 85 of 108 coronary territories (79%, kappa = 0.26). With contrast
      enhanced RT3DE, agreement increased to 95 of 108 coronary territories (88%, kappa
      = 0.59). Study agreement on myocardial ischemia was present in 26 of 36 studies
      (72%, kappa = 0.43) with conventional RT3DE and in 32 of 36 studies (89%, kappa =
      0.77) with contrast-enhanced RT3DE. In conclusion, during stress RT3DE, contrast
      enhanced imaging significantly decreases the number of poorly visualized
      myocardial segments and improves interobserver agreement for the diagnosis of
      myocardial ischemia.

PMID- 17223434
TI  - Accuracy of electrocardiographic-gated versus nongated volumetric intravascular
      ultrasound measurements of coronary arterial narrowing.
AB  - Intravascular ultrasound (IVUS) allows precise measurements of plaque plus media
      (P+M) volume and neointimal hyperplasia after coronary artery stenting.
      Conventional IVUS volumetric analysis is performed mostly without
      electrocardiographically gated acquisition, and the IVUS images are selected at 1
      mm intervals, whereas the electrocardiographically gated approach consists of
      images in end-diastole. The accuracy in the luminal, P+M, and external elastic
      membrane (EEM) volumes between 2 pullbacks with the electrocardiographically
      gated and nongated approaches has not previously been compared. In 15 patients,
      19 segments were studied with electrocardiographically gated and nongated IVUS
      systems. Two identical pullbacks were performed with each system using the same
      IVUS catheter. Volumes of the lumen, EEM, and P+M obtained using the
      electrocardiographically gated pullback technique did not differ significantly
      from the corresponding volumes obtained using the nongated pullback technique
      (lumen: 109.7 +/- 47.7 vs 109.2 +/- 45.0 mm(3), p = NS; EEM: 242.6 +/- 109.2 vs
      235.0 +/- 108.1 mm(3), p = NS; P+M: 134.8 +/- 67.7 vs 129.8 +/- 69.1 mm(3), p =
      NS). No significant differences were seen in changes between 2
      electrocardiographically gated and 2 nongated pullbacks (lumen: 0.37 +/- 1.76 vs 
      0.23 +/- 2.32 mm(3), p = NS; EEM: 0.25 +/- 3.22 vs -0.94 +/- 4.27 mm(3), p = NS;
      P+M: -0.18 +/- 3.42 vs -0.74 +/- 3.88 mm(3), p = NS). In conclusion, in moderate
      atherosclerotic or stented coronary arteries, electrocardiographically gated IVUS
      acquisition is not superior in accuracy to conventional nongated IVUS
      acquisition.

PMID- 17223435
TI  - An orwellian discourse on the meaning and measurement of noninferiority.
AB  - The customary interpretation of active-controlled noninferiority trials is
      founded on a number of unverifiable assumptions. These assumptions can be
      circumvented, and the semantic and statistic interpretation of the trials placed
      on a more rational foundation, if treatment comparisons are analyzed from a
      Bayesian perspective. In conclusion, the resultant probabilistic measures thereby
      render the meaning of noninferiority more transparent and clinically relevant.

PMID- 17223436
TI  - Assessment of bleeding events in clinical trials--proposal of a new
      classification.
AB  - Present classifications of bleeding events used in antithrombotic and/or
      antiplatelet clinical trials are based on the criteria developed by the
      Thrombolysis In Myocardial Infarction (TIMI) and Global Use of Strategies to Open
      Coronary Arteries (GUSTO) groups. Introduced more than a decade ago, the 2
      classifications used the criteria to better categorize hemorrhagic events after
      therapy with thrombolytic agents. Recent advances in interventional cardiology,
      resulting in a domination of percutaneous intracoronary procedures over systemic
      drug-induced thrombolysis, have substantially changed the clinical
      characteristics and magnitude of bleeding complications. Moreover, disturbances
      of the coagulation cascade, as well as platelet inhibition caused directly by
      antithrombotic and antiplatelet agents, share very specific and well-recognized
      clinical features not reflected in the existing classifications. Bleeding events
      after aspirin or clopidogrel, and especially those after more delicate
      antiplatelet regimens with dipyridamole used in patients after ischemic stroke or
      transient ischemic attack, are impossible to classify by the present guidelines,
      other than categorically triaging them altogether to the "minor" category.
      Uniting entirely different bleeding events as "minor" under-rates their
      importance and diminishes affiliated risks, creating an illusion that they do not
      require monitoring and/or changes in antiplatelet or antithrombotic regimens. In
      reality, such unrecognized and unreported mild complications may transform into
      more serious bleeds or lead to noncompliance. Unauthorized withdrawal from
      antiplatelet agents in turn causes rebound platelet activation and higher risk
      for secondary vascular events. In conclusion, a new classification of bleeding
      events is introduced (the BleedScore), based on a point accumulation depending on
      the severity of hemorrhage, which is believed to be more suitable for the
      assessment of modern, more delicate antithrombotic and antiplatelet therapies,
      particularly for their realistic assessment in clinical trials.

PMID- 17223437
TI  - Monday, Wednesday, and Friday dosing of rosuvastatin in patients previously
      intolerant to statin therapy.
AB  - Statins are normally administered for the treatment of dyslipidemia on a daily
      basis. This standard dosing regimen is well tolerated by most patients.
      Occasionally, patients discontinue therapy secondary to side effects, most
      commonly myalgias. We describe 2 patients who were unable to tolerate daily
      atorvastatin therapy secondary to myalgias and were subsequently treated with
      rosuvastatin administered on Mondays, Wednesdays, and Fridays, with resolution of
      adverse effects. Significant reductions in serum low-density lipoprotein
      cholesterol levels were observed in the 2 patients despite the alternate-day
      dosing regimen. Rosuvastatin was chosen because of its long half-life (19 hours)
      and very high potency.

PMID- 17223438
TI  - Carcinoid heart disease in patients without hepatic metastases.
AB  - Most carcinoid tumors originate in the gut. Carcinoid heart disease typically
      occurs when tumor progression results in the formation of hepatic metastases,
      which allow vasoactive substances to reach the heart without being metabolized in
      the liver. Except for patients with primary ovarian carcinoid tumors, the
      occurrence of carcinoid heart disease without hepatic metastases has been
      reported only anecdotally. From a retrospective analysis of 265 patients, 4
      patients were identified who developed carcinoid heart disease in the absence of
      liver metastases or primary tumors located in the ovaries. All 4 patients had
      metastases to the retroperitoneal lymph nodes and had carcinoid syndrome. The
      reasons for referral to cardiac evaluation by transthoracic echocardiography were
      findings on auscultation in 3 patients and exertional dyspnea in 1 patient. In
      conclusion, cardiac symptoms or findings on auscultation should prompt further
      evaluation by transthoracic echocardiography in these patients, although the
      classic prerequisites for development of carcinoid heart disease are lacking.

PMID- 17223439
TI  - Targeting an old mechanism in a new disease-protection of glutamatergic
      dysfunction in depression.

PMID- 17223444
TI  - Clinical efficacy supporting the role of intraperitoneal drug delivery in the
      primary chemotherapeutic management of small-volume residual advanced ovarian
      cancer.
AB  - Delivery of chemotherapeutic agents directly into the peritoneum to treat tumors
      localized to the abdominal cavity is a concept tested initially in clinical
      practice in the early 1950s. However, thorough investigation of the drawbacks and
      potential of intraperitoneal (IP) drug administration was not explored until the
      late 1970s. After fading in popularity, three major phase III randomized trials
      (SWOG 8501/GOG 104, GOG 114, and GOG 172) have helped IP therapy to resurface as
      an acceptable alternative for selected stage III ovarian cancer patients with
      optimally debulked tumors. These trials have provided overwhelming evidence
      supporting the value of IP strategy in prolonging progression-free and overall
      survival rates. GOG 172 showed a remarkable 15.9 month increase in median overall
      survival for the IP arm in comparison to the intravenous arm. This review article
      discusses the clinical data available from these three Gynecologic Oncology Group
      (GOG) studies (SWOG 8501/GOG 104, GOG 114, and GOG 172), supporting the use of a
      combination of IP and intravenous chemotherapy in patients with stage III ovarian
      cancer after surgical debulking.

PMID- 17223440
TI  - Regulation of glycogen synthase kinase-3 in patients with affective disorders.

PMID- 17223445
TI  - Maximizing the delivery of intraperitoneal therapy while minimizing drug toxicity
      and maintaining quality of life.
AB  - This decade has witnessed three large randomized trials (SWOG 8501/GOG 104, GOG
      114, and GOG 172) clearly showing the advantages of intraperitoneal (IP)
      chemotherapy over systemic/intravenous therapy in treating selected patients with
      advanced stage ovarian cancer. Despite showing an impressive increase in median
      progression-free survival and median overall survival, complications in IP
      chemotherapy delivery and drug-related toxicities reported in these studies have
      hindered widespread acceptance and implementation of first-line IP therapy. Some
      of these complications and drug-related toxicities are treatment-limiting and
      need special attention. Success of IP therapy as a first-line choice of treatment
      is dependent upon ideal patient selection, effective delivery of appropriate
      doses of chemotherapy agents to the tumor site, and efficient management of
      complications. With proper orientation and instruction in IP catheter placement
      and patient management, these obstacles can be overcome, allowing for successful
      administration of IP therapies. This review article discusses clinical approaches
      to maximize the delivery of IP therapy while minimizing catheter complications.
      Mitigating drug toxicities with the use of cytoprotectants such as amifostine and
      preventing infection with the use of agents, such as amifostine and
      pegfilgrastim, are discussed in detail.

PMID- 17223446
TI  - New and emerging intraperitoneal (IP) drugs for ovarian cancer treatment.
AB  - Chemotherapy after surgical debulking represents an essential component of
      treatment for patients with advanced ovarian cancer. Three quarters of patients
      respond very well to initial treatment with platinum-containing drugs used either
      alone or in combination with a taxane, usually paclitaxel. With relapse rates
      exceeding 50% and median survival time of 2 years for patients after relapse,
      efforts are focused on treatment approaches to achieve and extend clinical
      complete remissions. These approaches include consolidation and maintenance
      therapy, intraperitoneal (IP) administration of cytotoxic agents, new combination
      chemotherapy regimens, development of new cytotoxic agents, and molecular
      targeted therapies (beyond tumor DNA, the classical target of cytotoxic drugs).
      IP chemotherapy, which involves direct instillation of chemotherapy into the
      tumor site in the peritoneal cavity, is the focus of this review article. This
      article discusses studies involving new and emerging IP drugs for both first-line
      chemotherapy treatment of advanced ovarian cancer and recurrent platinum
      sensitive ovarian cancer.

PMID- 17223448
TI  - Democrats on drugs.

PMID- 17223447
TI  - Concluding remarks: optimal treatment for women with ovarian cancer.

PMID- 17223449
TI  - Combating civilian deaths and restoring health in Iraq.

PMID- 17223450
TI  - Ashley's treatment: unethical or compassionate?

PMID- 17223451
TI  - Can telomere length predict cardiovascular risk?

PMID- 17223452
TI  - Simplifying treatment for children with ALL.

PMID- 17223453
TI  - Syphilis resurgent in China.

PMID- 17223454
TI  - Phenotype and coronary outcome in Kawasaki's disease.

PMID- 17223456
TI  - Increased transparency in EU pharmaceutical code.

PMID- 17223455
TI  - Living kidney donation and hypertension risk.

PMID- 17223457
TI  - Quite reasonably emotional.

PMID- 17223459
TI  - Gilbert Burnham.

PMID- 17223461
TI  - Mortality in Iraq.

PMID- 17223462
TI  - Mortality in Iraq.

PMID- 17223463
TI  - Mortality in Iraq.

PMID- 17223464
TI  - Mortality in Iraq.

PMID- 17223465
TI  - Mortality in Iraq.

PMID- 17223467
TI  - Mortality in Iraq.

PMID- 17223468
TI  - Mortality in Iraq.

PMID- 17223469
TI  - Prevention of vascular events in atrial fibrillation.

PMID- 17223470
TI  - Health in foreign policy.

PMID- 17223471
TI  - Prevention of vascular events in atrial fibrillation.

PMID- 17223473
TI  - Telomere length, risk of coronary heart disease, and statin treatment in the West
      of Scotland Primary Prevention Study: a nested case-control study.
AB  - BACKGROUND: Inter-individual differences in biological ageing could affect
      susceptibility to coronary heart disease. Our aim was to determine whether mean
      leucocyte telomere length is a predictor of the development of coronary heart
      disease. METHODS: We compared telomere lengths at recruitment in 484 individuals
      in the West of Scotland Primary Prevention Study (WOSCOPS) who went on to develop
      coronary heart disease events with those from 1058 matched controls who remained
      event free. We also investigated whether there was any association between
      telomere length and observed clinical benefit of statin treatment in WOSCOPS.
      FINDINGS: Mean telomere length decreased with age by 9% per decade (95% CI 3.6
      14.1; p=0.001) in controls; much the same trend was seen in cases (-5.9% per
      decade, -3.1 to 14.1; p=0.1902). Individuals in the middle and the lowest
      tertiles of telomere length were more at risk of developing a coronary heart
      disease event than were individuals in the highest tertile (odds ratio [OR] for
      coronary heart disease: 1.51, 95% CI 1.15-1.98; p=0.0029 in the middle tertile;
      1.44, 1.10-1.90, p=0.0090 in the lowest). In placebo-treated patients, the risk
      of coronary heart disease was almost double in those in the lower two tertiles of
      telomere length compared with those in the highest tertile (1.93, 1.33-2.80,
      p=0.0005 in the middle tertile; 1.94, 1.33-2.84, p=0.0006 in the lowest). By
      contrast, in patients treated with pravastatin, the increased risk with shorter
      telomeres was substantially attenuated (1.12, 0.75-1.69, p=0.5755 in the middle
      tertile; 1.02, 0.68-1.52, p=0.9380 in the lowest). INTERPRETATION: Mean leucocyte
      telomere length is a predictor of future coronary heart disease events in middle
      aged, high-risk men and could identify individuals who would benefit most from
      statin treatment. Our findings lend support to the hypothesis that differences in
      biological ageing might contribute to the risk--and variability in age of onset-
      of coronary heart disease.

PMID- 17223474
TI  - Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis
      of individual patients' data.
AB  - BACKGROUND: Despite three decades of prenatal screening for congenital
      toxoplasmosis in some European countries, uncertainty remains about the
      effectiveness of prenatal treatment. METHODS: We did a systematic review of
      cohort studies based on universal screening for congenital toxoplasmosis. We did
      a meta-analysis using individual patients' data to assess the effect of timing
      and type of prenatal treatment on mother-to-child transmission of infection and
      clinical manifestations before age 1 year. Analyses were adjusted for gestational
      age at maternal seroconversion and other covariates. FINDINGS: We included 26
      cohorts in the review. In 1438 treated mothers identified by prenatal screening,
      we found weak evidence that treatment started within 3 weeks of seroconversion
      reduced mother-to-child transmission compared with treatment started after 8 or
      more weeks (adjusted odds ratio [OR] 0.48, 95% CI 0.28-0.80; p=0.05). In 550
      infected liveborn infants identified by prenatal or neonatal screening, we found
      no evidence that prenatal treatment significantly reduced the risk of clinical
      manifestations (adjusted OR for treated vs not treated 1.11, 95% CI 0.61-2.02).
      Increasing gestational age at seroconversion was strongly associated with
      increased risk of mother-to-child transmission (OR 1.15, 95% CI 1.12-1.17) and
      decreased risk of intracranial lesions (0.91, 0.87-0.95), but not with eye
      lesions (0.97, 0.93-1.00). INTERPRETATION: We found weak evidence for an
      association between early treatment and reduced risk of congenital toxoplasmosis.
      Further evidence from observational studies is unlikely to change these results
      and would not distinguish whether the association is due to treatment or to
      biases caused by confounding. Only a large randomised controlled clinical trial
      would provide clinicians and patients with valid evidence of the potential
      benefit of prenatal treatment.

PMID- 17223475
TI  - Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for
      children with intermediate-risk acute lymphoblastic leukaemia: a multicentre
      randomised trial.
AB  - BACKGROUND: Studies in the 1970s and 1980s suggested that the outcome of
      childhood acute lymphoblastic leukaemia (ALL) could be improved by
      intensification of conventional continuation chemotherapy with pulses of
      vincristine sulfate and steroids. We aimed to investigate the efficacy and toxic
      effects of vincristine-dexamethasone pulses as an addition to the continuation
      therapy phase in a large cohort of children with intermediate-risk disease who
      were treated with the Berlin-Frankfurt-Munster (BFM) treatment strategy. METHODS:
      3109 children, diagnosed with ALL and intermediate-risk features, were enrolled
      by eight participating organisations in eleven countries. All were treated with
      very similar protocols based on the BFM treatment strategy, which included
      induction, consolidation, reinduction, and continuation-therapy phases. At the
      beginning of the continuation-therapy phase, those patients in complete remission
      were randomly assigned to either a treatment or a control group. Control patients
      were given conventional mercaptopurine and methotrexate chemotherapy only.
      Patients in the treatment arm were also given pulses of vincristine (1.5 mg/m2
      weekly for 2 weeks) and dexamethasone (6 mg/m2 daily for 7 days) every 10 weeks
      for six cycles. The primary outcome measure was disease-free survival. Analysis
      was by intention to treat. The study is registered at
      http://www.clinicaltrials.gov with the identifier NCT00411541. FINDINGS: 174
      patients (5.6%) relapsed or died in complete remission before randomisation. Of
      the remaining 2935 patients, 2618 (89.2%) were randomly assigned: 1325 to the
      treatment group and 1293 to the control group. With median follow-up of 4.8
      years, 240 children in the treatment group and 241 in the control group had
      relapses; 15 in the treatment group and 14 controls died in complete remission or
      developed second malignant neoplasms. The 5-year and 7-year disease-free survival
      estimates were 79.8% (SE 1.2) and 77.5% (1.5) in the treatment group and 79.2%
      (1.2) and 78.4% (1.3) in the control group, respectively. Treatment with pulses
      of vincristine and dexamethasone was associated with a non-significant 3%
      relative-risk reduction (hazard ratio 0.97; 95% CI 0.81-1.15; p=0.70).
      INTERPRETATION: Children with intermediate-risk ALL who received intensive
      chemotherapy based on BFM protocols did not benefit from intensification of the
      continuation-therapy phase with a schedule of pulses of vincristine and
      dexamethasone.

PMID- 17223476
TI  - Syphilis in China: results of a national surveillance programme.
AB  - BACKGROUND: After a massive syphilis epidemic in the first half of the 20th
      century, China was able to eliminate this infection for 20 years (1960-80).
      However, substantial changes in Chinese society have been followed by a resurgent
      epidemic of sexually transmitted diseases. Sporadic reports have provided clues
      to the magnitude of the spread of syphilis, but a national surveillance effort is
      needed to provide data for planning and intervention. METHODS: We collected and
      assessed case report data from China's national sexually transmitted disease
      surveillance system and sentinel site network. FINDINGS: In 1993, the reported
      total rate of cases of syphilis in China was 0.2 cases per 100,000, whereas
      primary and secondary syphilis alone represented 5.7 cases per 100,000 persons in
      2005. The rate of congenital syphilis increased greatly with an average yearly
      rise of 71.9%, from 0.01 cases per 100,000 livebirths in 1991 to 19.68 cases per
      100 000 livebirths in 2005. INTERPRETATION: The results suggest that a range of
      unique biological and social forces are driving the spread of syphilis in China.
      A national campaign for detection and treatment of syphilis, and a credible
      prevention strategy, are urgently needed.

PMID- 17223477
TI  - Post-traumatic stress disorder: medicine and politics.
AB  - Regrettably, exposure to trauma is common worldwide, and can have serious adverse
      psychological results. The introduction of the notion of post-traumatic stress
      disorder has led to increasing medicalisation of the problem. This awareness has
      helped popular acceptance of the reality of post-traumatic psychiatric sequelae,
      which has boosted research into the pathogenesis of the disorder, leading to
      improved pharmacological and psychological management. The subjective experience
      of trauma and subsequent expression of symptoms vary considerably over space and
      time, and we emphasise that not all psychological distress or psychiatric
      disorders after trauma should be termed post-traumatic stress disorder. There are
      limits to the medicalisation of distress and there is value in focusing on
      adaptive coping during and after traumas. Striking a balance between a focus on
      heroism and resilience versus victimhood and pathological change is a crucial and
      constant issue after trauma for both clinicians and society. In this Review we
      discuss the advantages and disadvantages of medicalising trauma response, using
      examples from South Africa, the Armed Services, and post-disaster, to draw
      attention to our argument.

PMID- 17223478
TI  - Child development: risk factors for adverse outcomes in developing countries.
AB  - Poverty and associated health, nutrition, and social factors prevent at least 200
      million children in developing countries from attaining their developmental
      potential. We review the evidence linking compromised development with modifiable
      biological and psychosocial risks encountered by children from birth to 5 years
      of age. We identify four key risk factors where the need for intervention is
      urgent: stunting, inadequate cognitive stimulation, iodine deficiency, and iron
      deficiency anaemia. The evidence is also sufficient to warrant interventions for
      malaria, intrauterine growth restriction, maternal depression, exposure to
      violence, and exposure to heavy metals. We discuss the research needed to clarify
      the effect of other potential risk factors on child development. The prevalence
      of the risk factors and their effect on development and human potential are
      substantial. Furthermore, risks often occur together or cumulatively, with
      concomitant increased adverse effects on the development of the world's poorest
      children.

PMID- 17223479
TI  - Patient safety and patient error.

PMID- 17223480
TI  - Disseminated tuberculosis after anti-TNFalpha treatment.

PMID- 17223482
TI  - Resuscitation great: Benjamin Howard and the direct method of artificial
      respiration.

PMID- 17223483
TI  - Bayesian learning of sparse gene regulatory networks.
AB  - Differential equations (DEs) have been the most widespread formalism for gene
      regulatory network (GRN) modeling, as they offer natural interpretation of
      biological processes, easy elucidation of gene relationships, and the capability
      of using efficient parameter estimation methods. However, an important limitation
      of DEs is their requirement of O(d(2)) parameters where d is the number of genes
      modeled, which often causes over-parameterization for large d, leading to the
      over-fitting of data and dense parameter sets that are hard to interpret. This
      paper presents the first effort to address the over-parameterization problem by
      applying the sparse Bayesian learning (SBL) method to sparsify the GRN model of
      DEs. SBL operates on the parsimony principle, with the objective to reduce the
      number of effective parameters by driving the redundant parameters to zero. The
      resulting sparse parameter set offers three important advantages for GRN
      inference: first, the inferred GRNs are more plausible, since the biological
      counterparts are known to be sparse; second, gene relationships can be more
      easily elucidated from sparse sets than from dense sets; and third, the solutions
      become more optimal and consistent, due to the reduction in the volume of
      solution space. Experiments are conducted on the yeast Saccharomyces cerevisiae
      time-series gene expression data, in which known regulatory events related to the
      cell cycle G1/S phase are reliably reproduced.

PMID- 17223484
TI  - Respiratory management of inhalation injury.
AB  - Advances in the care of patients with major burns have led to a reduction in
      mortality and a change in the cause of their death. Burn shock, which accounted
      for almost 20 percent of burn deaths in the 1930s and 1940s, is now treated with
      early, vigorous fluid resuscitation and is only rarely a cause of death. Burn
      wound sepsis, which emerged as the primary cause of mortality once burn shock
      decreased in importance, has been brought under control with the use of topical
      antibiotics and aggressive surgical debridement. Inhalation injury has now become
      the most frequent cause of death in burn patients. Although mortality from smoke
      inhalation alone is low (0-11 percent), smoke inhalation in combination with
      cutaneous burns is fatal in 30 to 90 percent of patients. It has been recently
      reported that the presence of inhalation injury increases burn mortality by 20
      percent and that inhalation injury predisposes to pneumonia. Pneumonia has been
      shown to independently increase burn mortality by 40 percent, and the combination
      of inhalation injury and pneumonia leads to a 60 percent increase in deaths.
      Children and the elderly are especially prone to pneumonia due to a limited
      physiologic reserve. It is imperative that a well organized, protocol driven
      approach to respiratory care of inhalation injury be utilized so that
      improvements can be made and the morbidity and mortality associated with
      inhalation injury be reduced.

PMID- 17223485
TI  - Burn patient characteristics and outcomes following resuscitation with albumin.
AB  - BACKGROUND: Use of colloids in acute burn resuscitation may reduce fluid
      requirements, but effect on mortality is unknown. We hypothesized that patients
      who received albumin would have similar mortality to patients who did not receive
      albumin. METHODS: We performed a case-controlled study of inpatients who
      sustained burns of > or =20% total body surface area (TBSA). Patients who
      received albumin during resuscitation because of increased fluid requirements
      (ALB) were compared to a cohort of patients matched for age and TBSA who did not
      receive albumin (CON). RESULTS: Patients with inhalation injury were
      significantly more likely to receive albumin (OR 4.89, 95% CI 2.58-9.30). ALB
      patients had significantly higher mean initial lactate (3.64 versus 2.29,
      p=0.01), longer mean time to resuscitation (52.8 h versus 36.3 h; p=0.001), and
      higher resuscitation volume (9.4 mL/kg/%TBSA versus 6.4 mL/kg/%TBSA for CON).
      Mortality was not significantly different between the two groups (OR 1.90, 95% CI
      0.85-4.22). Albumin was protective in a multivariate model of mortality (OR 0.27,
      95% CI 0.07-0.97). CONCLUSIONS: Despite more severe systemic dysfunction, burn
      patients who received albumin did not suffer increased mortality. A novel finding
      is the decreased likelihood of mortality associated with the administration of
      albumin during burn resuscitation.

PMID- 17223486
TI  - Burns in Sweden: an analysis of 24,538 cases during the period 1987-2004.
AB  - Burn care is always progressing, but there is little epidemiological information
      giving a clear picture of the current number of treated burns in Sweden. This
      study was conducted to provide an update of patients admitted to hospital with
      burns in Sweden. Data were obtained for all patients who were admitted to
      hospitals with a primary or secondary diagnosis of burns (ICD-9/10 codes) from 1
      January 1987 to 31 December 2004; 24,538 patients were found. Most of the
      patients were male (69%), giving a male:female ratio of 2.23:1. Children in the
      age-group 0-4 years old predominated, and accounted for 27% of the study
      material. The median length of stay was 3 days. Throughout the period 740
      patients (3%) died of their burns. Significant reductions in mortality,
      incidence, and length of stay were seen during the study, which correlates well
      with other studies. However, most of the reductions were in the younger age
      groups. Men accounted for the improved mortality, as female mortality did not
      change significantly. We think that the improvement in results among patients
      admitted to hospital after burns is a combination of preventive measures,
      improved treatment protocols, and an expanding strategy by which burned patients
      are treated as outpatients.

PMID- 17223487
TI  - A study of regional nerve blocks and local anesthetic creams (Prilox) for donor
      sites in burn patients.
AB  - BACKGROUND: Burn patient requires multiple visits to the operation theatres and
      undergoing anesthesia with its attendant risks and post anesthesia recovery. It
      is possible now with the availability of local anesthetic creams like Prilox to
      conduct these procedures in the minor OT without any discomfort to the patient.
      MATERIALS AND METHODS: Hundred patients of post burn raw areas were selected.
      These patients had at least one area of healthy skin on anterior, medial or
      lateral thigh. No patient had a known drug allergy. The age group varied from 5
      to 75 years with no bias towards any sex. These patients were then given
      anesthesia according to the group, and were assessed for the ease of grafting,
      amount of graft being harvested, subjective pain score, post operative pain
      relief and any post operative complication. The nerve block technique being used
      was either femoral and/or LCT block or 3-in-1 block and popliteal fossa block.
      RESULTS: Both the group of patients had a virtual painless process of skin
      grafting. It is safe in selected patients to combine the two techniques in order
      to harvest larger areas. DISCUSSION: Both techniques of local anesthestic creams
      and nerve block are safe and convenient to use. Nerve blocks are more useful
      where larger grafts are required, the creams being more useful in children and
      where less graft is required.

PMID- 17223488
TI  - Transformations in doctor-patient communication in Japan: the role of cultural
      factors.

PMID- 17223489
TI  - Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC
      II).

PMID- 17223490
TI  - Resource and environmental management in islands.

PMID- 17223493
TI  - Non-invasive diagnosis of cirrhosis and the natural history of its complications.
AB  - Several methods have been studied in the attempt to reach a diagnosis of
      cirrhosis by non-invasive means. Although abdominal ultrasound can detect the
      hepatic and extra-hepatic changes consistent with cirrhosis, its ability to
      distinguish chronic hepatitis from compensated cirrhosis is limited. Serum
      markers can rule in or rule out fibrosis in up to 35% of patients but, in
      individual patients, cannot differentiate the stages of fibrosis reliably.
      Transient elastography (Fibroscan) might be of value for the non-invasive
      diagnosis of cirrhosis; however, its reproducibility needs to be further
      validated. Cirrhosis can be divided into 4 stages: stage 1, no varices, no
      ascites; stage 2, varices without ascites and without bleeding; stage 3,
      ascites+/-varices; stage 4, bleeding+/-ascites. Yearly mortality ranges from 1%
      in stage 1 to 57% in stage 4. The yearly incidence of oesophageal varices is 5
      7%; their rate of enlargement is 10-12% per year. The incidence of variceal
      bleeding is about 25% at 2 years. Bleeding stops spontaneously in about 50% of
      cases but early rebleeding occurs in 30-40% of patients. Bleeding-related
      mortality has declined over time and is now around 20% at 6 weeks.

PMID- 17223494
TI  - Management of acute bleeding from portal hypertension.
AB  - Gastrointestinal bleeding is a frequent and severe complication of portal
      hypertension. The most frequent cause of the bleeding is variceal rupture.
      Despite improvements in prognosis after variceal bleeding over the past two
      decades, the 6-week mortality rate remains high, ranging from 15 to 30%. Patients
      die from uncontrolled bleeding, early rebleeding, infection, or renal failure
      within the first weeks of a bleeding episode. Poor hepatic function, severe
      portal hypertension with a hepatic venous pressure gradient (HVPG) >20 mmHg, and
      active bleeding at endoscopy are independently associated with poor prognosis.
      First-line treatment includes resuscitation, prophylactic antibiotic therapy, the
      combined use of vasoactive drugs (started as soon as possible), and an endoscopic
      procedure. Reconstitution of blood volume should be done cautiously to maintain
      the haematocrit between 25 and 30%. Terlipressin, somatostatin, or octreotide can
      be used, and drug therapy is maintained from 48 h to 5 days. Ligation is the
      endoscopic treatment of choice in bleeding oesophageal varices; in gastric
      varices, obturation with cyanoacrylate is preferable. Uncontrolled bleeding
      should be an indication for a salvage transjugular portosystemic shunt (TIPS). In
      patients with Child-Pugh score A, shunt surgery might be an alternative to TIPS.
      Trials are currently ongoing into the precise indications of early TIPS in
      selected patients with an HVPG >20 mmHg, and into the usefulness of
      administration of recombinant activated factor VII when there is an active
      bleeding at endoscopy.

PMID- 17223495
TI  - Prevention of the development of varices and first portal hypertensive bleeding
      episode.
AB  - Variceal bleeding is a serious complication in patients with cirrhosis. Although
      bleeding related mortality rates have fallen recently, it continues to be amongst
      the leading causes of death. Cirrhotics should be screened for varices at
      diagnosis. Data on preventing formation/growth of oesophageal varices (pre
      primary prophylaxis) are conflicting, with insufficient evidence to use beta
      blockers. In order to prevent first bleeding, there is strong evidence in
      patients with medium/large size oesophageal varices that either non-selective
      beta-blockers or banding ligation can be used. Banding is superior with respect
      to bleeding but mortality is similar. Non-selective beta-blockers should remain
      first line treatment being effective, cheap and without serious complications. In
      contrast banding ligation is more expensive, requires specialised staff, cannot
      prevent bleeding from portal hypertensive gastropathy and can cause iatrogenic
      bleeding. Patients with small varices, particularly if they have progressive
      liver disease also benefit from beta-blockers, but fewer studies confirm this
      therapeutic approach.

PMID- 17223496
TI  - Prevention of recurrent haemorrhage.
AB  - Patients who survive a first bleeding episode of oesophageal varices have a high
      risk of rebleeding, which is associated with a high mortality rate. Prevention of
      a recurrent haemorrhage is therefore recommended. Patients who were not on a
      primary prophylaxis should be treated with non-selective beta-adrenoceptor
      antagonists, endoscopic band ligation or both. If beta-blockers are not tolerated
      or are contraindicated, patients should be treated with endoscopic band ligation.
      If these preventive strategies fail, transjugular intrahepatic portosystemic
      shunt (covered) or a small-diameter surgical shunt is indicated.

PMID- 17223497
TI  - Management of ascites and hepatic hydrothorax.
AB  - The natural course of patients with cirrhosis is frequently complicated by the
      accumulation of fluid in the peritoneal or pleural cavities and interstitial
      tissue. Functional renal abnormalities that occur as a consequence of decreased
      effective arterial blood volume are responsible for fluid accumulation in the
      form of ascites and hepatic hydrothorax. Ascites is the most common complication
      of cirrhosis and poses an increased risk for infections, renal failure and
      mortality. Patients have a poor prognosis and it is estimated that nearly half
      will die in approximately 2 years without liver transplantation. Hepatic
      hydrothorax is defined as a pleural effusion greater than 500 mL (mostly right
      sided) in patients with cirrhosis without cardiopulmonary disease; the estimated
      prevalence is approximately 5-10%. Liver transplantation is the most definitive
      cure for both conditions in those patients that are suitable candidates. However,
      the mainstay of therapy for minimizing fluid accumulation in both conditions
      includes sodium restriction and administration of diuretics. This article reviews
      the most current concepts of pathogenesis, clinical findings, diagnosis, and
      treatment of these complications of cirrhosis.

PMID- 17223498
TI  - Prevention and treatment of infections in patients with cirrhosis.
AB  - Patients with cirrhosis have altered immune defenses and are considered
      immunocompromised individuals. Changes in gut motility, mucosal defense and
      microflora allow for translocation of enteric bacteria into mesenteric lymph
      nodes and the blood stream. Additionally, the cirrhotic liver is ineffective at
      clearing bacteria and associated endotoxins from the blood thus allowing for
      seeding of the sterile peritoneal fluid. Thus, hospitalised cirrhotic patients,
      particularly those with gastrointestinal hemorrhage, are at high risk of
      developing bacterial infections, the most common being spontaneous bacterial
      peritonitis. Given the significant morbidity and mortality associated with
      spontaneous bacterial peritonitis and the fact that half of the cases are
      community acquired, all hospitalised cirrhotic patients should have a diagnostic
      paracentesis to exclude infection. Those admitted with gastrointestinal bleed and
      a negative paracentesis require short-term prophylaxis with norfloxacin. A third
      generation cephalosporin is the treatment of choice for spontaneous bacterial
      peritonitis and, once the acute infection is resolved, secondary prophylaxis with
      oral norfloxacin is warranted. Patients who develop renal dysfunction at the time
      of active infection have the highest mortality and require adjunctive albumin
      therapy. This article reviews the pathogenesis of SBP, the evidence behind the
      antibiotics used, the rationale for adjunctive albumin therapy in the setting of
      acute renal failure, and the role of prophylactic antibiotics in specific high
      risk populations.

PMID- 17223499
TI  - Management of hepatic encephalopathy in patients with cirrhosis.
AB  - The term hepatic encephalopathy encompasses a spectrum of neuropsychiatric
      abnormalities seen in patients with liver dysfunction. Distinct syndromes are
      identified in acute liver failure and cirrhosis. Rapid deterioration in
      consciousness level and increased intracranial pressure that may result in brain
      herniation and death are a feature of acute liver failure whereas manifestations
      of hepatic encephalopathy in cirrhosis include psychomotor dysfunction, impaired
      memory, increased reaction time, sensory abnormalities, poor concentration and in
      severe forms, coma. In patients with acute-on-chronic liver failure the
      pathophysiology remains undefined. Ammonia has been considered central to its
      pathogenesis. In the brain, the astrocyte is the main site for ammonia
      detoxification, during the conversion of glutamate to glutamine. An increased
      ammonia level raises the amount of glutamine within astrocytes, causing an
      osmotic imbalance resulting in cell swelling and ultimately brain oedema. Recent
      studies suggest that inflammation and it modulators may play a synergistic role
      with ammonia in the pathogenesis of hepatic encephalopathy. Therapy of hepatic
      encephalopathy is directed primarily at reducing ammonia generation and
      increasing its detoxification. The currently accepted regimens to treat hepatic
      encephalopathy such as lactulose and protein restricted diets need further
      clinical trials and therefore placebo controlled clinical trials in hepatic
      encephalopathy are justified. In liver failure, ammonia metabolism involves
      multiple organs and therefore ammonia reduction will require simultaneous
      targeting of these organs. The present review describes the pathophysiological
      basis of hepatic encephalopathy and evaluates the available therapies.

PMID- 17223500
TI  - Diagnosis and treatment of acute renal failure in patients with cirrhosis.
AB  - In patients with cirrhosis, acute renal failure is due to prerenal failure (a
      result of decreased renal perfusion) and tubular necrosis. There are 3 main
      causes of prerenal failure: 'true hypovolemia' (which complicates hemorrhage,
      gastrointestinal or renal fluid losses), sepsis, and type 1 hepatorenal syndrome
      (HRS). Prerenal failure may also be due to the administration of non-steroidal
      antiinflammatory drugs, or intravascular radiocontrast agents. Prerenal failure
      is reversible after restoration of renal blood flow. Treatments target the cause
      of hypoperfusion, and fluid replacement is used to treat 'non-HRS' prerenal
      failure. In patients with type 1 HRS with very low short-term survival rate,
      liver transplantation is the ideal treatment. Systemic vasoconstrictor therapy
      with terlipressin (combined with intravenous human albumin), noradrenaline
      (combined with albumin and furosemide) or midodrine (combined with octreotide and
      albumin) may improve renal function in patients with type 1 HRS waiting for liver
      transplantation. MARS (for Molecular Adsorbent Recirculating System) and the
      transjugular intrahepatic portosystemic shunt may also improve renal function in
      these patients. In patients with cirrhosis, acute tubular necrosis is mainly due
      to an ischemic insult to the renal tubules. Studies are needed on the natural
      course and treatment (e.g., renal-replacement therapy) of acute tubular necrosis
      in patients with cirrhosis.

PMID- 17223501
TI  - Cardiac dysfunction in cirrhosis.
AB  - Cirrhosis is known to be associated with numerous cardiovascular abnormalities.
      These include increased cardiac output and decreased arterial pressure and total
      peripheral resistance. Despite this increased baseline cardiac output, patients
      with cirrhosis show an attenuated systolic and diastolic function in the face of
      pharmacological, physiological and surgical stresses, as well as cardiac
      electrical abnormalities such as QT prolongation. These abnormalities have been
      termed cirrhotic cardiomyopathy. The pathogenic mechanisms that underlie this
      syndrome include impairment of the beta-adrenergic receptor signalling,
      cardiomyocyte plasma membrane function, intracellular calcium kinetics, and
      humoral factors such as endogenous cannabinoids, nitric oxide and carbon
      monoxide. Cirrhotic cardiomyopathy is believed to contribute to the cardiac
      dysfunction that can be observed in patients with transjugular intrahepatic
      portosystemic stent-shunt insertion and liver transplantation. Insufficient
      cardiac contractile function may also play a role in the pathogenesis of
      hepatorenal syndrome precipitated by spontaneous bacterial peritonitis. In this
      review, the clinical features, pathogenic mechanisms, clinical consequences and
      management options for cirrhotic cardiomyopathy are discussed.

PMID- 17223502
TI  - Pulmonary vascular abnormalities in cirrhosis.
AB  - Two pulmonary vascular disorders can occur in liver disease and/or portal
      hypertension: the hepatopulmonary syndrome (HPS), which is characterized by
      intrapulmonary vascular dilatations, and portopulmonary hypertension (POPH), in
      which pulmonary vascular resistance is elevated. POPH and HPS are characterized
      by distinct pulmonary microvascular remodelling, which occurs at different
      anatomical sites of the pulmonary microcirculation. The exact pathophysiological
      mechanisms of these pulmonary vascular disorders are unknown. However, as HPS and
      POPH have been reported in patients with extrahepatic portal hypertension, the
      factor that determines their development must be portal hypertension. The
      clinical presentations are very different, with gas exchange impairment in HPS
      and hemodynamic failure in POPH. The severity of HPS seems to parallel the
      severity of liver failure, whereas no simple relationship has been identified
      between hepatic impairment and the severity of POPH. Resolution of HPS is common
      after liver transplantation, which has an uncertain effect in POPH.

PMID- 17223503
TI  - Hepatocellular carcinoma development in cirrhosis.
AB  - The development of hepatocellular carcinoma (HCC), the mechanisms of
      hepatocarcinogenesis, the prevention of HCC, and screening for HCC will be
      discussed. Cirrhosis has been considered as a pre-neoplastic condition for the
      development of HCC. The worldwide incidence of HCC differs according to different
      hepatitis viruses, and information is lacking. Hepatocarcinogenesis is a
      multistep process involving a number of different genetic alterations and is
      poorly understood. Interferon should help prevent the development of HCC in
      patients with chronic hepatitis C. Screening is the only practical approach for
      improving the management of HCC patients, as early detection increases the
      application of curative treatments. However, the cost-effectiveness of various
      screening strategies needs to be analysed.

PMID- 17223504
TI  - Indications of liver transplantation in patients with complications of cirrhosis.
AB  - Transplantation is the only option for reversing liver insufficiency and its
      complications in patients with end-stage cirrhosis. Transplantation is generally
      considered after the first episode of decompensation of cirrhosis, provided no
      specific intervention can result in a longstanding return to the compensated
      state. Alcohol abuse and hepatitis C virus infection are the predominant causes
      leading to transplantation in Western countries. In cases of alcoholic cirrhosis,
      a 6-month period of abstinence is needed before transplantation. Patients with
      hepatitis C virus infection are considered independent of viral replication, even
      if post-transplantation recurrence is almost constant. Conversely, in cases of
      hepatitis B infection, only patients without viral replication (or with extremely
      low viral load) are suitable candidates. Hepatocellular carcinoma represents an
      increasing proportion of the indications and offers excellent long-term survival.
      However, transplantation should be limited to patients with small tumours. HIV
      infection no longer represents a definitive contraindication.

PMID- 17223505
TI  - The future treatment of portal hypertension.
AB  - Increased understanding of the hyperdynamic circulation syndrome has resulted in
      novel therapeutic approaches, some of which have already reached clinical
      practice. Central to the hyperdynamic circulation syndrome is an imbalance
      between the increase in different vasodilators (foremost among which is nitric
      oxide) and the compensatory increase in vasoconstrictors--usually accompanied by
      a blunted response. This chapter discusses the role of endothelin in the
      pathogenesis of the syndrome and in future treatment approaches. A relatively new
      area of research in this field is the role of infection and inflammation in the
      initiation and maintenance of the hyperdynamic circulation syndrome. The use of
      antibiotics in the setting of acute variceal bleeding is standard practice.
      Studies have suggested that chronic manipulation of the intestinal flora could
      have beneficial effects in the treatment of portal hypertension. The bile salts
      are another novel and interesting target. Although their vasoactive properties
      have been known for some time, recent data demonstrate that their effects could
      be central in the pathogenesis of the hyperdynamic circulation syndrome, and that
      manipulation of the composition of the bile acid pool could be a therapeutic
      approach to portal hypertension. Finally, hypoxia and angiogenesis play a role in
      the development of portal hypertension and the formation of collaterals. This
      role needs to be further defined but it appears likely that this phenomenon is
      yet another target for therapeutic intervention.

PMID- 17223507
TI  - Delayed acetyl-L-carnitine administration and its effect on sensory neuronal
      rescue after peripheral nerve injury.
AB  - Protection of sensory neurons after peripheral nerve injury is clinically crucial
      since inadequate sensory recovery is seriously affected by the death of up to 40%
      of sensory neurons. Immediate acetyl-L-carnitine (ALCAR) treatment eliminates
      this cell loss, but may not always be clinically feasible, hence we studied the
      effect of delaying the initiation of ALCAR treatment. Five groups of rats (n=5
      per group) underwent unilateral sciatic nerve axotomy. ALCAR treatment (50
      mg/kg/day) was initiated immediately, or after delays of 6 h, 24 h or 7 days
      after injury. A sham-treated group served as control. L4 and L5 dorsal root
      ganglia were harvested bilaterally 2 weeks after injury and stereological sensory
      neuron counts were obtained. Immediate sham treatment provided no neuroprotection
      (25% loss). Cell loss was eliminated when ALCAR was commenced within<or=24 h of
      axotomy. No statistically significant neuroprotective effect (18% loss) was
      evident compared to sham when ALCAR administration was initiated 7 days post
      axotomy. When commenced within a clinically applicable time frame ALCAR treatment
      remains highly neuroprotective, potentially improving clinical outcome following
      peripheral nerve trauma.

PMID- 17223506
TI  - Considerations in evaluating new treatment alternatives following peripheral
      nerve injuries: a prospective clinical study of methods used to investigate
      sensory, motor and functional recovery.
AB  - The current problem finding reliable and objective methods for evaluating results
      after peripheral nerve repair is a challenge when introducing new clinical
      techniques. The aim of this study was to obtain reference material and to
      evaluate the applicability of different tests used for clinical assessment after
      peripheral nerve injuries. Fifteen patients with a history of complete median
      nerve transsection and repair, and 15 healthy volunteers were included. Each
      subject was investigated using a battery of conventional and new tests for
      functional, sensory and motor recovery including questionnaires, clinical
      evaluations, neurophysiological and physiological findings. The results were
      statistically analysed and comparisons were made within the patient group and
      between patients and healthy volunteers using a 'per protocol' and an 'intention
      to treat' approach. Criteria for success were stipulated in order to be able to
      judge the usefulness of each method. The results showed that 19 of 34 variables,
      representing six of 16 methods, were not able to fulfil the criteria and were
      thus questionable for the evaluations of nerve repair in a clinical trial
      setting. However, 2pd, sensory recovery according to the non-modified British
      Medical Research Council, sensory neurography, manual muscle test,
      electromyography, questionnaires (i.e. DASH and the 4 question form) and
      performance tests (i.e. AMPS and Sollerman's subtests 4 and 8) did fulfil the
      criteria defined for being useful.

PMID- 17223508
TI  - The sagittal curving osteotomy: a modified technique for advancement genioplasty.
AB  - PURPOSE: The purpose of the present study was to develop a new type of osteotomy
      for advancement genioplasty to decrease the incidence of neurosensory disturbance
      of the chin. PATIENTS AND METHOD: Forty-six patients who suffered from a slight
      or moderate degree of microgenia received a sagittal curving osteotomy for
      advancement genioplasty. Patients were followed for 1-6 months to assess the
      neurosensory function of the chin region by evaluating light-touch perception.
      The control group, 57 patients, who suffered from the same degree of microgenia,
      received a horizontal sliding osteotomy. They were operated on by the same
      surgical group and were followed for 1-33 months. RESULTS: All of the test and
      control patients were satisfied with the aesthetic results of the surgery. In the
      test group, 47 sides (51.87%) of 92 total left and right sides of chins had a
      transient neurosensory deficiency but none had permanent neurosensory deficiency.
      In the control group, 98 sides (86.84%) of 114 total chin sides had a transient
      neurosensory deficiency and five sides (4.43%) of 114 total chin sides had
      permanent neurosensory deficiency. When applied to patients who suffer from a
      mild or moderate degree of microgenia and have normal bite function, the sagittal
      curving osteotomy is a simple, safe and effective technique for advancement
      genioplasty. This technique can distinctively decrease the incidence of
      neurosensory disturbance of the chin.

PMID- 17223509
TI  - The volume of muscles of mastication in patients receiving mandibular contouring
      surgery: a comparative study.
AB  - PURPOSE: As the management of prominent mandibular angle and masseter muscle
      hypertrophy becomes increasingly popular, proper understanding of the volumetric
      component of the related structures becomes important but is currently lacking.
      MATERIALS AND METHODS: Three-dimensional computed tomographic (CT) scans of 18
      female and eight male adult patients with square-face appearance were used for
      volumetric measurement of the osseous hemi-mandible, masseter, medial and lateral
      pterygoid muscles. CT scans of 28 female and 17 male adult patients without
      square-face appearance were selected from the imaging laboratory archive to serve
      as controls. RESULTS: Compared with the sex-matched controls, the square-faced
      patients had significantly higher volume of the osseous hemi-mandible as well as
      the masseter and medial pterygoid muscles. There was no significant difference in
      the volume of the lateral pterygoid muscle between the two groups. This study
      confirms a significantly greater volume in the osseous mandible and masseter
      muscle in patients complaining of square-face appearance. The implication of this
      information on treatment is discussed.

PMID- 17223510
TI  - Soft tissue facial volumes and shape in skeletal Class III patients before and
      after orthognathic surgery treatment.
AB  - BACKGROUND: To obtain the best surgical results in orthognathic surgery,
      treatment planning and the evaluation of results should be performed on
      measurable three-dimensional reproductions of the face of the patients, and
      compared to reference subjects. METHODS: Seven women aged 18-35 years, all with a
      skeletal Class III and mandibular asymmetry, were assessed both before (on
      average, 2 months) and after (on average, 10.7 months) surgical intervention
      (mandibular reduction by sagittal split osteotomy and LeFort I maxillary
      advancement). The three-dimensional coordinates of 50 soft tissue facial
      landmarks (face, eyes, nose, mouth and lips, ears) were collected with a
      noninvasive, electromagnetic digitizer; facial volumes were estimated, and
      compared to reference values collected in 87 healthy women of the same age and
      ethnic group. Inter-individual modifications in facial shape were also assessed.
      RESULTS: Before surgery the patients had smaller faces than the reference women,
      with larger lower lips and noses. A large within-group variability was found.
      Surgical treatment significantly reduced total facial volume and mandibular
      volume, increased total and upper lip volumes (Student's t test, p<0.05), and
      made all values more homogenous within the group. Shape differences were
      significantly larger before than after surgery. On average, right side gonion was
      the landmark that moved the most, closely followed by menton, while the tragi and
      ala nasi moved the least. The three-dimensional approach used in this study
      enabled quantitative evaluation of the final soft tissue results of surgery,
      without submitting the patients to invasive procedures.

PMID- 17223511
TI  - Skeletal changes after modified intraoral vertical ramus osteotomy for correction
      of mandibular prognathism.
AB  - BACKGROUND: Orthognathic surgery is widely used to correct congenital and
      acquired dentofacial discrepancies. Various surgical procedures have been
      advocated for correction of mandibular prognathism. In this study, a modified
      intraoral vertical ramus osteotomy has been developed for surgical correction of
      mandibular prognathism. The aim of this study is to identify contributing factors
      to skeletal change by analysing cephalometric changes after modified intraoral
      vertical ramus osteotomy. METHODS: Forty-one patients, treated for absolute
      mandibular prognathism by bilateral modified intraoral vertical ramus osteotomy,
      were evaluated cephalometrically with reference to the menton point. A set of
      four standardised lateral cephalograms were obtained from each subject
      preoperatively (T1) and immediately postoperatively (T2), prior to removal of
      maxillomandibular fixation (T3), and at 1-year postoperatively (T4). The mean
      setback of the menton was 12.4 mm in the horizontal direction. Relapse was
      defined as forward movement of the menton during the 1-year follow-up. RESULTS:
      The highly significant backward movements in a horizontal direction were observed
      during the maxillomandibular fixation period (T3-T2). Moreover, highly
      significant forward movement was observed following the maxillomandibular
      fixation period (T4-T3). After 1-year follow-up (T4-T2), the mean changes of the
      menton were 0.1 mm backward in the horizontal direction. CONCLUSIONS: In this
      series, the mean skeletal change compared with the amount of setback was less
      than 1% (0.1/12.4 mm) in backward movement. The results suggest that the modified
      intraoral vertical ramus osteotomy technique is useful and the more stable
      approach for correction of severe mandibular prognathism.

PMID- 17223512
TI  - The conservative management of facial fractures: indications and outcomes.
AB  - BACKGROUND: With little in the published literature on the conservative
      management of facial fractures we set out to determine whether our current
      criteria for treatment are valid. METHOD: Two hundred and thirty adult patients
      with fractures of the facial skeleton were treated conservatively by our unit
      between February 1997 and January 2003. Their notes were reviewed
      retrospectively. RESULTS: Most patients were males (76%), the average age was 38
      years, and drugs or alcohol were a significant aspect of the history in 30% of
      the cases. The most common mechanism of injury was assault (47%), followed by
      falls and sporting injuries. Fifty percent of the fractures involved the orbital
      or orbito-zygomatic complex, and 55% had associated injuries. Average follow-up
      was for six weeks (range 0-44 weeks). Most patients were managed conservatively
      based on our current criteria of un-displaced/minimally displaced fracture (57%);
      or minimal/no symptoms (24%). At final review, a number had residual symptoms,
      but only three required corrective surgery. The other reasons for conservative
      management included patient non-compliance (11%), and medical contraindications
      (8%). CONCLUSION: Our results support current indications for the conservative
      management of facial fractures, but emphasise the need for ongoing follow-up of
      these patients.

PMID- 17223513
TI  - Reconstructive surgery of the leprosy nose: a new approach.
AB  - There has still been no reduction in the detection rate worldwide for leprosy,
      despite supervised multi-drug therapy. In time, leprosy can result in a severe
      saddle-nose deformity leading to functional problems, disfiguration and
      stigmatization. In severe cases, only the nasal skin tissue and the lower lateral
      cartilages are preserved. In such cases, the ideal would be to restore the
      cartilaginous skeleton but, by contrast with other causes of saddle-nose
      deformities, this is complicated by the quantity and the poor quality of the
      remaining nasal mucosa. Leprosy-related saddle-nose deformities are therefore
      challenging and difficult to reconstruct with the techniques that have been
      proposed in the past. In this study, 24 patients underwent rhinoplastic surgery
      involving the use of autogenous costal and/or auricular cartilage or composite
      grafts. The nasal septum, the upper laterals and the anterior nasal spine were
      reconstructed with a dorsal onlay attached to a columellar strut with an
      extension on the proximal side. Before surgery, the saddle-nose deformities were
      classified according to severity with a new system based on clinical symptoms and
      signs. Postoperative evaluation was performed at least two years after surgery
      (N=17). Functional and aesthetic improvement, resorption rate, warping, infection
      and extrusion were analysed. Functional and aesthetic improvements were achieved
      in 15/17 patients. None of the patients developed an infection and extrusion or
      warping of the implants was not observed. The resorption rate depended on the
      localization and the type of cartilage implant. In general, auricular conchal
      cartilage implant grafts resulted in less resorption than costal cartilage. Least
      resorption (4/17 patients) was observed in the dorsal onlay grafts of both
      conchal (1/6) and costal cartilage grafts (3/11). Resorption of columellar strut
      implants and shield grafts was observed in 7/17 patients. No resorption was seen
      of composite grafts (0/4) and alar battens (0/7). Autogenous cartilage implants
      can be used to reconstruct saddle-nose deformities in leprosy with a minimum risk
      of complications. The preoperative grade of severity was used as a basis for the
      development of guidelines for optimal long-term functional and aesthetic outcome.

PMID- 17223514
TI  - Correction of the nasal tip and columella in Koreans by a complete septal
      extension graft using an extensive harvesting technique.
AB  - The nose of most Koreans is characterised by a low nasal dorsum, retracted
      columella, and an acute columella-labial angle. For the surgical correction of
      the tip and columella, a complete septal extension graft, along with augmentation
      rhinoplasty has been developed. However, the use of this type of graft is
      frequently problematic because the septal cartilage is not large enough. In a
      study involving 10 cadavers, a complete septal extension graft was achieved in
      two of them by using septal cartilage harvested according to standard techniques.
      Therefore, the septal cartilage was harvested, leaving a 5-mm L-shaped strut, and
      a complete septal extension graft was implanted. The present report describes the
      results obtained in 34 patients and offers an analysis of the results as judged
      by the columella-labial angle and three proportional indices (nose height index,
      nasal bridge length index, and nasal tip projection index), measured by
      photogrammetry. The postoperative values obtained in these four categories
      increased significantly compared to the preoperative ones, thus confirming that
      the projection of tip was augmented, the nose was lengthened, and the columella
      was advanced caudally. Moreover, these positive outcomes were maintained during
      long-term follow-up, and no side effects, such as saddle nose deformity, were
      reported.

PMID- 17223515
TI  - Combined use of triple cartilage grafts in secondary rhinoplasty.
AB  - Secondary rhinoplasty on a patient with a middle vault deformity is one of the
      most challenging procedures for a plastic surgeon. In order to achieve proper
      nasal aesthetics and airway function, a surgeon most commonly chooses to engraft
      the nose with a spreader, dorsal onlay, or columellar graft. This paper examines
      the aforementioned techniques in the management of 25 patients who presented with
      a severe middle nasal vault deformity. METHODS: During the last 5 years, 25
      patients received secondary rhinoplasty using triple cartilage grafts to repair
      severe middle vault deformities. Patients were then questioned at least 3 months
      postoperatively about both airway problems and cosmetic satisfaction. RESULTS:
      All the 25 patients indicated cosmetic satisfaction with 23 of the patients also
      achieving complete nasal airway function. Only two patients persisted to have an
      insufficient nasal airway. An endonasal examination revealed a slight nasal
      synechiae in one patient, while no anatomic problem was identified in the second
      patient. From a cosmetic standpoint, a straight dorsum with improved dorsal
      aesthetic lines and nasal profile, along with nasal-facial balance were achieved.
      When indicated, secondary rhinoplasty to repair a middle vault deformity using
      the combination of spreader, dorsal onlay, and columellar grafts to augment the
      nose has shown to have both functional and cosmetic benefits.

PMID- 17223516
TI  - Correction of the Asian deviated nose with no hump using unilateral bony
      mobilisation and dorsal septal suture fixation.
AB  - A deviated nose is corrected by straight realignment and long-term maintenance of
      the bony and cartilaginous structure. Traditional rhinoplasty usually involves
      complete separation of both upper lateral cartilages from the septum and
      bilateral bony mobilisation after osteotomy. In the Asian deviated nose with no
      hump, these procedures are intrinsically destabilising and may weaken the
      supporting bony and cartilaginous structure. To avoid these problems, I performed
      unilateral bony mobilisation with anterior wedge resection and suture fixation of
      the dorsal septum to the nasal bone without separation of the upper lateral
      cartilage. This manoeuvre is simple and reproducible and produces satisfactory
      straightening and maintenance of the nasal dorsum while maximally preserving the
      structural support. Here, I describe the surgical techniques including the choice
      of the site of unilateral osteotomy and wedge resection, a new classification of
      bony deviation, two surgical modifications applied to different types of
      deviation and rationale of dorsal septal suture fixation. Also, clinical cases of
      nasal deviation are presented.

PMID- 17223517
TI  - The conchal cartilage graft in nasal reconstruction.
AB  - Graft selection remains a problem in nasal reconstruction, where the use of
      autologous cartilage still provides the best resistance to infection and a low
      degree of resorption. As the nasal septum is often absent or insufficient in such
      patients, the auricular concha offers a valid alternative. A group of 53 patients
      suffering from developmental iatrogenic and post-traumatic nasal pathologies were
      treated surgically by means of conchal grafts. Detailed examination of the
      anatomical defects presented by the patients made it possible to plan the removal
      of grafts from the area of the auricular concha with great precision. Guidelines
      were developed for the areas of the cymba concha and cavum concha to be used as
      sources for some types of commonly used graft. The technique described made it
      possible to restore the anatomically deficient structures with satisfactory
      aesthetic and reconstructive results. The use of cartilage grafts also addressed
      functional breathing problems. The auricular concha is easy to shape and can
      provide grafts to reconstruct the various anatomical components of the nasal
      pyramid. To this end, it proves very useful to save as much cartilage as possible
      and to pinpoint affinities between some areas of the concha and the structures to
      be reconstructed.

PMID- 17223518
TI  - Small incision subperiosteal and trans-blepharoplasty forehead and browlift.
AB  - The purpose of the study is to evaluate the safety and efficacy of non
      endoscopic, small-incision subperiosteal forehead and browlift in patients
      undergoing associated upper eyelid blepharoplasty. This is a retrospective, non
      comparative case series of 14 consecutive patients in 12 months. Eleven patients
      underwent bilateral and three unilateral surgery. Unilateral surgery was
      performed in patients with facial palsy and was augmented with cable suspension.
      The technique involves five small scalp incisions to create a single
      subperiosteal and deep temporal cavity. Superior arcus marginalis release and
      direct visualisation of the supraorbital nerve was achieved via a trans
      blepharoplasty approach. All patients achieved a desirable browlift and contour.
      Follow up ranged from 2 to 40 weeks. Minor complications included transient
      diplopia (1), reduced upper eyelid sensation (1), and brief postoperative
      bleeding from one of the small incision sites (1). Small incision and trans
      blepharoplasty forehead and browlift is a safe and effective method to achieve a
      cosmetically desirable browlift in patients that require associated upper eyelid
      blepharoplasty, using standard oculoplastic equipment without the need for an
      endoscope.

PMID- 17223519
TI  - Repositioning of posterior auricular muscle combined with conventional otoplasty:
      a personal technique.
AB  - Prominent ears are the most common deformity of the external ear in children.
      Since 1881 various treatments have been described but the choice of procedure
      still remains at the surgeon's preference. A posterior auricular muscle
      malposition is frequently present in prominent ear deformity even though this
      muscle shows only a rudimentary function in man. This article presents a
      technique to reposition the posterior auricular muscle as an adjunct to
      conventional otoplasty. A quadrangular cartilage paddle, where the muscle
      inserts, is raised with the muscle as a chondro-muscular flap that can be
      advanced and reset more peripherally. Eighty consecutive patients, followed up
      for at least 12 months, have been reviewed. The posterior auricular muscle
      repositioning combined with a lozenge shaped conchectomy has been successfully
      performed in 103 ears. The cartilage paddle proved to be a strong support which
      facilitates the re-insertion of the muscle. Repositioning of posterior auricular
      muscle allows a more anatomical correction of both ear's projection and slope
      improving symmetry with the contralateral side.

PMID- 17223520
TI  - Successful separation of pygopagus conjoined twins and primary skin closure using
      V-shaped flaps.
AB  - Pygopagus conjoined twins were born by caesarean section at 34 weeks of
      gestation. Initial evaluation revealed no other abnormalities apart from their
      attachment at lower back, buttocks and perineum. They had two separate anal and
      urogenital openings. Their investigations included roentgenograms, ultrasound,
      barium enema, cystourethrogram, CT scan and MRI. There were two separate spinal
      columns fused distally at the lower sacral level. Lower gastrointestinal studies
      showed two separate rectums and cystourethrogram showed normal and separate
      urinary tracts. MRI showed a single dural sac between two fused sacral bones with
      no other vertebral anomalies. They were successfully separated with primary skin
      closure using V-shaped flaps.

PMID- 17223521
TI  - A late complication following the insertion of hydrogel breast implants.
AB  - This case report draws attention to an unusual presentation and subsequent
      complication following the insertion of a PIP Hydrogel implant for breast
      augmentation. A cutaneous and capsular foreign body giant cell reaction was
      identified, and was preceded by the development of a notable increase in breast
      volume prior to spontaneous discharge. We believe that this was caused by
      subclinical leakage of the implant contents through a degrading shell. The
      biodegradability of hydrogel makes it impossible to ascertain the precise nature
      of the material that leaked out. Given this demonstrable leakage, the adverse
      clinical effects and the potential for toxicity that is currently unknown, we
      question whether this product (and other hydrogel breast implants like it) should
      be formally recalled for the benefit of patient safety.

PMID- 17223522
TI  - 'Fish mouth' modification for enhancing the advancement of V-Y flap.

PMID- 17223523
TI  - In response to 'facial transplantation: a new gold standard in facial
      reconstruction?'.

PMID- 17223524
TI  - A helpful tip to reduce the incidence of possible implant contamination and
      capsule formation in breast augmentation.

PMID- 17223525
TI  - Searchlight on domains.
AB  - In this issue of Structure, examine in detail the functions of selected domains
      within proteins both when they are alone and when in combination with others.
      Domain function is relevant to molecular evolution and to annotation of proteins
      known only by sequence.

PMID- 17223526
TI  - Tying the knot that binds.
AB  - The recent determination of protein structures with knots in their backbone
      topology has defied previous conventional wisdom. How proteins can fold with a
      knot is an intriguing question that has been explored for YibK from Haemophilus
      influenzae in this issue of Structure.

PMID- 17223527
TI  - Bypassing translation initiation.
AB  - A high-resolution cryo-EM reconstruction of a ribosome-bound dicistrovirus IRES
      (Schuler et al., 2006) and the crystal structure of its ribosome binding domain
      (Pfingsten et al., 2006) provide new insights into an exceptional eukaryotic
      translation mechanism.

PMID- 17223529
TI  - Structural and thermodynamic principles of viral packaging.
AB  - Packaging of genetic material inside a capsid is one of the major processes in
      the lifecycle of bacteriophages. To establish the basic principles of packing
      double-stranded DNA into a phage, we present a low-resolution model of
      bacteriophage varphi29 and report simulations of DNA packaging. The simulations
      show excellent agreement with available experimental data, including the forces
      of packaging and the average structures seen in cryo-electron microscopy. The
      conformation of DNA inside the bacteriophage is primarily determined by the shape
      of the capsid and the elastic properties of DNA, but the energetics of packaging
      are dominated by electrostatic repulsions and the large entropic penalty
      associated with DNA confinement. In this slightly elongated capsid, the DNA
      assumes a folded toroidal conformation, rather than a coaxial spool. The model
      can be used to study packaging of other bacteriophages with different shapes
      under a range of environmental conditions.

PMID- 17223528
TI  - Identification of secondary structure elements in intermediate-resolution density
      maps.
AB  - An increasing number of structural studies of large macromolecular complexes,
      both in X-ray crystallography and cryo-electron microscopy, have resulted in
      intermediate-resolution (5-10 A) density maps. Despite being limited in
      resolution, significant structural and functional information may be extractable
      from these maps. To aid in the analysis and annotation of these complexes, we
      have developed SSEhunter, a tool for the quantitative detection of alpha helices
      and beta sheets. Based on density skeletonization, local geometry calculations,
      and a template-based search, SSEhunter has been tested and validated on a variety
      of simulated and authentic subnanometer-resolution density maps. The result is a
      robust, user-friendly approach that allows users to quickly visualize, assess,
      and annotate intermediate-resolution density maps. Beyond secondary structure
      element identification, the skeletonization algorithm in SSEhunter provides
      secondary structure topology, which is potentially useful in leading to
      structural models of individual molecular components directly from the density.

PMID- 17223530
TI  - Atomic resolution structures of rieske iron-sulfur protein: role of hydrogen
      bonds in tuning the redox potential of iron-sulfur clusters.
AB  - The Rieske [2Fe-2S] iron-sulfur protein of cytochrome bc(1) functions as the
      initial electron acceptor in the rate-limiting step of the catalytic reaction.
      Prior studies have established roles for a number of conserved residues that
      hydrogen bond to ligands of the [2Fe-2S] cluster. We have constructed site
      specific variants at two of these residues, measured their thermodynamic and
      functional properties, and determined atomic resolution X-ray crystal structures
      for the native protein at 1.2 A resolution and for five variants (Ser-154-->Ala,
      Ser-154-->Thr, Ser-154-->Cys, Tyr-156-->Phe, and Tyr-156-->Trp) to resolutions
      between 1.5 A and 1.1 A. These structures and complementary biophysical data
      provide a molecular framework for understanding the role hydrogen bonds to the
      cluster play in tuning thermodynamic properties, and hence the rate of this
      bioenergetic reaction. These studies provide a detailed structure-function
      dissection of the role of hydrogen bonds in tuning the redox potentials of [2Fe
      2S] clusters.

PMID- 17223531
TI  - Biochemical implications of a three-dimensional model of monomeric actin bound to
      magnesium-chelated ATP.
AB  - Actin structure is of intense interest in biology due to its importance in cell
      function and motility mediated by the spatial and temporal regulation of actin
      monomer-filament interconversions in a wide range of developmental and disease
      states. Despite this interest, the structure of many functionally important actin
      forms has eluded high-resolution analysis. Due to the propensity of actin
      monomers to assemble into filaments structural analysis of Mg-bound actin
      monomers has proven difficult, whereas high-resolution structures of actin with a
      diverse array of ligands that preclude polymerization have been quite successful.
      In this work, we provide a high-resolution structural model of the Mg-ATP-actin
      monomer using a combination of computational methods and experimental
      footprinting data that we have previously published. The key conclusion of this
      study is that the structure of the nucleotide binding cleft defined by subdomains
      2 and 4 is essentially closed, with specific contacts between two subdomains
      predicted by the data.

PMID- 17223532
TI  - All-atom ab initio folding of a diverse set of proteins.
AB  - Natural proteins fold to a unique, thermodynamically dominant state. Modeling of
      the folding process and prediction of the native fold of proteins are two major
      unsolved problems in biophysics. Here, we show successful all-atom ab initio
      folding of a representative diverse set of proteins by using a minimalist
      transferable-energy model that consists of two-body atom-atom interactions,
      hydrogen bonding, and a local sequence-energy term that models sequence-specific
      chain stiffness. Starting from a random coil, the native-like structure was
      observed during replica exchange Monte Carlo (REMC) simulation for most proteins
      regardless of their structural classes; the lowest energy structure was close to
      native-in the range of 2-6 A root-mean-square deviation (rmsd). Our results
      demonstrate that the successful folding of a protein chain to its native state is
      governed by only a few crucial energetic terms.

PMID- 17223533
TI  - Structure of the Bateman2 domain of yeast Snf4: dimeric association and relevance
      for AMP binding.
AB  - AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis
      in mammals. AMP is believed to control the activity of AMPK by binding to the
      gamma subunit of this heterotrimeric enzyme. This subunit contains two Bateman
      domains, each of which is composed of a tandem pair of cystathionine beta
      synthase (CBS) motifs. No structural information is currently available on this
      subunit, and the molecular basis for its interactions with AMP is not well
      understood. We report here the crystal structure at 1.9 Angstrom resolution of
      the Bateman2 domain of Snf4, the gamma subunit of the yeast ortholog of AMPK. The
      structure revealed a dimer of the Bateman2 domain, and this dimerization is
      supported by our light-scattering, mutagenesis, and biochemical studies. There is
      a prominent pocket at the center of this dimer, and most of the disease-causing
      mutations are located in or near this pocket.

PMID- 17223534
TI  - DNA recognition mechanism of the ONECUT homeodomain of transcription factor HNF
      6.
AB  - Hepatocyte nuclear factor-6 (HNF-6), a liver-enriched transcription factor,
      controls the development of various tissues, such as the pancreas and liver, and
      regulates the expression of several hepatic genes. This protein belongs to the
      ONECUT class of homeodomain proteins and contains a bipartite DNA-binding domain
      composed of a single cut domain and a characteristic homeodomain. This
      transcription factor has two distinct modes of DNA binding and transcriptional
      activation that use different coactivators depending on the target gene. The
      crystal structure of the bipartite DNA-binding domain of HNF-6alpha complexed
      with the HNF-6-binding site of the TTR promoter revealed the DNA recognition
      mechanism of this protein. Comparing our structure with the DNA-free structure of
      HNF-6 or the structure of Oct-1, we discuss characteristic features associated
      with DNA binding and the structural basis for the dual mode of action of this
      protein, and we suggest a strategy for variability of transcriptional activation
      of the target gene.

PMID- 17223535
TI  - The generation of new protein functions by the combination of domains.
AB  - During evolution, many new proteins have been formed by the process of gene
      duplication and combination. The genes involved in this process usually code for
      whole domains. Small proteins contain one domain; medium and large proteins
      contain two or more domains. We have compared homologous domains that occur in
      both one-domain proteins and multidomain proteins. We have determined (1) how the
      functions of the individual domains in the multidomain proteins combine to
      produce their overall functions and (2) the extent to which these functions are
      similar to those in the one-domain homologs. We describe how domain combinations
      increase the specificity of enzymes; act as links between domains that have
      functional roles; regulate activity; combine within one chain functions that can
      act either independently, in concert or in new contexts; and provide the
      structural framework for the evolution of entirely new functions.

PMID- 17223536
TI  - Divergent substrate-binding mechanisms reveal an evolutionary specialization of
      eukaryotic prefoldin compared to its archaeal counterpart.
AB  - Prefoldin (PFD) is a molecular chaperone that stabilizes and then delivers
      unfolded proteins to a chaperonin for facilitated folding. The PFD hexamer has
      undergone an evolutionary change in subunit composition, from two PFDalpha and
      four PFDbeta subunits in archaea to six different subunits (two alpha-like and
      four beta-like subunits) in eukaryotes. Here, we show by electron microscopy that
      PFD from the archaeum Pyrococcus horikoshii (PhPFD) selectively uses an
      increasing number of subunits to interact with nonnative protein substrates of
      larger sizes. PhPFD stabilizes unfolded proteins by interacting with the distal
      regions of the chaperone tentacles, a mechanism different from that of eukaryotic
      PFD, which encapsulates its substrate inside the cavity. This suggests that
      although the fundamental functions of archaeal and eukaryal PFD are conserved,
      their mechanism of substrate interaction have diverged, potentially reflecting a
      narrower range of substrates stabilized by the eukaryotic PFD.

PMID- 17223537
TI  - The dimerization of an alpha/beta-knotted protein is essential for structure and
      function.
AB  - alpha/beta-Knotted proteins are an extraordinary example of biological self
      assembly; they contain a deep topological trefoil knot formed by the backbone
      polypeptide chain. Evidence suggests that all are dimeric and function as
      methyltransferases, and the deep knot forms part of the active site. We
      investigated the significance of the dimeric structure of the alpha/beta-knot
      protein, YibK, from Haemophilus influenzae by the design and engineering of
      monomeric versions of the protein, followed by examination of their structural,
      functional, stability, and kinetic folding properties. Monomeric forms of YibK
      display similar characteristics to an intermediate species populated during the
      formation of the wild-type dimer. However, a notable loss in structure involving
      disruption to the active site, rendering it incapable of cofactor binding, is
      observed in monomeric YibK. Thus, dimerization is vital for preservation of the
      native structure and, therefore, activity of the protein.

PMID- 17223538
TI  - SR protein kinase 1 is resilient to inactivation.
AB  - SR protein kinase 1 (SRPK1) is a constitutively active kinase, which processively
      phosphorylates multiple serines within its substrates, ASF/SF2. We describe
      crystallographic, molecular dynamics, and biochemical results that shed light on
      how SRPK1 preserves its constitutive active conformation. Our structure reveals
      that unlike other known active kinase structures, the activation loop remains in
      an active state without any specific intraprotein interactions. Moreover, SRPK1
      remains active despite extensive mutation to the activation segment. Molecular
      dynamics simulations reveal that SRPK1 partially absorbs the effect of mutations
      by forming compensatory interactions that maintain a catalytically competent
      chemical environment. Furthermore, SRPK1 is similarly resistant to deletion of
      its spacer loop region. Based upon a model of SRPK1 bound to a segment
      encompassing the docking motif and active-site peptide of ASF/SF2, we suggest a
      mechanism for processive phosphorylation and propose that the atypical resiliency
      we observed is critical for SRPK1's processive activity.

PMID- 17223539
TI  - Ultrafast and downhill protein folding.
AB  - Ultrafast folding proteins have served an important role in benchmarking
      molecular dynamics simulations and testing protein folding theories. These
      proteins are simple enough and fold fast enough that realistic simulations are
      possible, which facilitates the direct comparison of absolute folding rates and
      folding mechanisms with those observed experimentally. Such comparisons have
      achieved remarkable success, but have also revealed the shortcomings that remain
      in experiment, theory and simulation alike. Some ultrafast folding proteins may
      fold without encountering an activation barrier (downhill folding), allowing the
      exploration of the molecular timescale of folding and the roughness of the energy
      landscape. The biological significance of ultrafast folding remains uncertain,
      but its practical significance is crucial to progress in understanding how
      proteins fold.

PMID- 17223540
TI  - HPV triage for low grade (L-SIL) cytology is appropriate for women over 35 in
      mass cervical cancer screening using liquid based cytology.
AB  - In the experimental arm of a randomised trial, women were tested both for liquid
      based cytology and human papillomavirus (HPV) DNA and referred for colposcopy if
      cytology was ASCUS (atypical cells of undetermined significance) or more severe.
      We considered those with ASCUS (757) or LSIL (low-grade squamous intraepithelial
      lesions) (485) and a valid HPV test who received colposcopy. We computed
      sensitivity, specificity and ROC curves with different values of relative light
      units (RLU, that are related to viral load) as cut off, using cervical
      intraepithelial neoplasia grade 2 or more severe (CIN2+) at blind histology
      review as the endpoint. The area under the receiver operating characteristic
      (ROC) curve was significantly less among women aged 25-34 years than in those
      older, both considering ASCUS/AGUS (atypical glandular cells of undetermined
      significance) (p=0.0355) and LSIL (p=0.0009). At age 35-60 the curves for ASCUS
      and LSIL were similar, while at age 25-34 the area under the curve for LSIL was
      significantly less than for ASCUS (p=0.0084). With LSIL cytology, specificity of
      Hybrid Capture 2 with 2 RLU cut-off was 35.0% (95%CI 28.4-42.1) at age 25-34 and
      64.5% (95%CI 58.3-70.3) at age 35-60. In conclusion, triaging by HPV testing
      performed better in women aged over 35 years than those younger. For older women,
      HPV triaging should also be considered for managing those with LSIL cytology.

PMID- 17223541
TI  - Progress and new standards of care in the management of HER-2 positive breast
      cancer.
AB  - The aim of this review article is to examine the available evidence regarding
      diagnosis and treatment of HER-2 positive breast cancer. This group of breast
      tumours (up to 30% of the total number of breast cancers) is known for having a
      more aggressive behaviour. The current recommendations for HER-2 positive tumour
      diagnosis are discussed since accurate identification of HER-2 amplification or
      overexpression is key for allowing a correct risk assessment and treatment. HER-2
      positive tumours can be treated with trastuzumab (Herceptin, Hoffmann-La Roche,
      Basel, Switzerland), a monoclonal antibody targeted against the HER-2 receptor.
      The role of this drug in the metastatic, adjuvant and neoadjuvant setting is
      reviewed. The results of the recently reported adjuvant trials are commented, as
      the positive results of these trials changed the standard of care for patients
      with this particular type of breast cancer.

PMID- 17223542
TI  - Who gets screened, and where: a comparison of organised and opportunistic
      mammography screening in Geneva, Switzerland.
AB  - It is unclear whether introducing organised mammography screening programmes in a
      population where opportunistic screening is prevalent results in the two types of
      screening mainly competing against each other or attracting different groups of
      women. To compare women who participate in organised screening and those who
      prefer opportunistic screening, we conducted a prospective study of 932 women
      followed for 8 months after an invitation to participate in the first round of an
      organised screening programme in Geneva, Switzerland. All women were aged 50-69
      years and were due for a mammogram according to local guideline. Of the 932
      participants, 11.6% had an organised and 39.4% an opportunistic mammogram during
      follow-up. Women who were in the stage of contemplation, had favourable attitude
      toward mammography screening, and perceived their risk of breast cancer to be
      high were more likely to have a mammogram (either organised or opportunistic).
      Compared to women who had an opportunistic mammogram, women with an organised
      mammogram were less positive about screening, less likely to be in maintenance at
      baseline (adjusted odds ratio (OR), 3.0; 95% confidence interval (CI), 1.7-5.5),
      to have a history of benign breast disease (OR, 2.4; 95% CI, 1.2-5.1) and to
      perceive their financial situation as comfortable (OR, 1.7; 95% CI, 1.1-2.8).
      Although screening uptake was low, the programme appeared to attract women in
      lower socio-economic strata who did not usually undergo mammography screening.

PMID- 17223543
TI  - Differential significance of tumour infiltrating lymphocytes in sporadic mismatch
      repair deficient versus proficient colorectal cancers: a potential role for
      dysregulation of the transforming growth factor-beta pathway.
AB  - The prognostic importance of tumour infiltrating lymphocytes (TILs) in colorectal
      cancer (CRC) remains controversial. The present study was undertaken to evaluate
      the role of TILs as prognostic indicators and to investigate the role of
      transforming growth factor-beta (TGF-beta) in TIL infiltration.
      Immunohistochemical staining for components in the TGF-beta pathway was performed
      on a tissue microarray of 1420 unselected CRCs with complete clinico-pathological
      data. Statistical analyses were carried out on samples stratified by mismatch
      repair (MMR) proficiency status and TIL counts. TIL infiltration was found to
      correlate with multiple clinico-pathological features but was a prognostic marker
      only in MMR proficient CRCs. In all CRCs, findings indicative of insensitivity to
      TGF-beta and increased TGF-beta secretion were independent predictors of high TIL
      counts, suggesting that perturbations in the TGF-beta signalling pathway play an
      important role in the recruitment and retention of TILs within CRC epithelium.

PMID- 17223544
TI  - Obesity and the risk of epithelial ovarian cancer: a systematic review and meta
      analysis.
AB  - Obesity is a risk factor for several hormone-related cancers but evidence for an
      effect on risk of epithelial ovarian cancer remains inconclusive. Many studies
      evaluating this association have had insufficient statistical power to detect
      modest effects, particularly for histological subtypes of ovarian cancer. We have
      therefore assembled the published evidence on obesity and ovarian cancer in a
      systematic literature review and meta-analysis. We identified eligible studies
      using Medline and manual review of retrieved references, and included all
      population-based studies that assessed the association between overweight, body
      mass index (BMI25-29.9) and obesity (BMI30) and histologically confirmed ovarian
      cancer. Meta-analysis was restricted to those studies that expressed effect as an
      odds ratio (OR), risk ratio, or standardised incidence ratio and 95% confidence
      interval (CI). We identified 28 eligible studies, of which 16 on adult obesity
      and 9 on obesity in early adulthood were suitable for meta-analysis. Overall, 24
      of 28 studies reported a positive association between obesity and ovarian cancer,
      and in 10 this reached statistical significance. The pooled effect estimate for
      adult obesity was 1.3 (95%CI1.1-1.5) with a smaller increased risk for overweight
      (OR1.2;95%CI1.0-1.3). The pooled OR was stronger among case-control studies
      (OR=1.5) than cohort studies (OR=1.1). Overweight/obesity in early adulthood was
      also associated with an increased risk of ovarian cancer. There was no evidence
      that the association varied for the different histological subtypes of ovarian
      cancer. Ovarian cancer should be added to the list of cancers likely to be
      related to obesity.

PMID- 17223546
TI  - 1alpha,25-Dihydroxyvitamin D and fish oil synergistically inhibit G1/S-phase
      transition in prostate cancer cells.
AB  - Laboratory and epidemiological studies have indicated that 1alpha,25
      dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)] and dietary omega3-polyunsaturated
      fatty acids (PUFAs) are capable of inhibiting prostate cancer at the initiation
      and progression stages. The objective of this study is to investigate the
      influence of 1alpha,25(OH)(2)D(3) and PUFAs in the form of fish oil applied alone
      or in combination on cell cycle kinetics in the exponentially growing androgen
      dependent and -independent prostate cancer cells. Our data indicate that the high
      passage androgen-independent cell line, LNCaP-c115 had a much greater inhibitory
      response at the level of the G(1)/S-phase transition in response to fish oil
      treatment than androgen-dependent low passage LNCaP-c38 cells. When LNCaP-c38 and
      LNCaP-c115 cells were treated with fish oil (50mug/ml), 1alpha,25(OH)(2)D(3) (10(
      8)M) or fish oil (50mug/ml)+1alpha,25(OH)(2)D(3) (10(-8)M), a synergistic growth
      inhibitory effect was observed with 1alpha,25(OH)(2)D(3)+fish oil group in LNCaP
      c115 cell line at the levels of the G(1)/S-phase transition and cell division.
      This interaction appears to be specific for androgen-independent prostate cancer
      cell lines. Based on these results, we hypothesize that dietary components, such
      as omega3PUFAs and Vitamin D, have the potential to delay the progression of
      prostate cancer cells to an aggressive and un-treatable state.

PMID- 17223545
TI  - Perspectives on mechanisms of gene regulation by 1,25-dihydroxyvitamin D3 and its
      receptor.
AB  - 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) functions as a systemic signal in
      vertebrate organisms to control the expression of genes whose products are vital
      to the maintenance of calcium and phosphorus homeostasis. This regulatory
      capability is mediated by the vitamin D receptor (VDR) which localizes at DNA
      sites adjacent to the promoter regions of target genes and initiates the complex
      events necessary for transcriptional modulation. Recent investigations using
      chromatin immunoprecipitation techniques combined with various gene scanning
      methodologies have revealed new insights into the location, structure and
      function of these regulatory regions. In the studies reported here, we utilized
      the above techniques to identify key enhancer regions that mediate the actions of
      vitamin D on the calcium ion channel gene TRPV6, the catabolic bone calcium
      mobilizing factor gene RankL and the bone anabolic Wnt signaling pathway co
      receptor gene LRP5. We also resolve the mechanism whereby 1,25(OH)(2)D(3)
      autoregulates the expression of its own receptor. The results identify new
      features of vitamin D-regulated enhancers, including their locations at gene
      loci, the structure of the VDR binding sites located within, their modular nature
      and their functional activity. Our studies suggest that vitamin D enhancers
      regulate the expression of key target genes by facilitating the recruitment of
      both the basal transcriptional machinery as well as the protein complexes
      necessary for altered gene expression.

PMID- 17223547
TI  - An analog of 1alpha,25-dihydroxy-19-norvitamin D3 with the 1alpha-hydroxy group
      fixed in the axial position lacks biological activity in vitro.
AB  - The relationship between the A-ring chair conformation of vitamin D compounds and
      their ability to bind the vitamin D receptor (VDR) has long attracted the
      attention of many researchers. It was established that in the crystalline
      complexes of hVDRmt with the natural hormone, 1alpha,25-dihydroxyvitamin D(3)
      (1), and its side-chain analogs the vitamins exist in beta-chair form with an
      equatorial orientation of 1alpha-OH. However, with all these ligands the
      interconversion between both A-ring forms would be possible in solution. In an
      attempt to verify the conformation of vitamin D compounds required for binding
      the VDR we prepared analog 4, characterized by the presence of an axial 1alpha
      hydroxy group. Since the additional ring connecting 3beta-oxygen and C-2 prevents
      A-ring conformational flexibility, the synthesized vitamin 4 can exist
      exclusively in the alpha-chair form. The geometrical isomer 5 with a free 3beta
      OH group was also obtained. The analog 5 binds very poorly to VDR, whereas the
      vitamin 4 is practically devoid of binding ability. Both compounds also show very
      low HL-60-differentiating activity. When tested in vivo in mice the analogs 4 and
      5 exhibit significant calcemic responses with analog 4 showing more activity than
      analog 5.

PMID- 17223548
TI  - Screening of Vitamin D activity (VDA) of Solanum glaucophyllum leaves measured by
      radioimmunoassay (RIA).
AB  - The ingestion of Solanum glaucophyllum (SG) causes a calcinosis of cattle named
      Enteque Seco (ES). The toxic principle is the 1,25-(OH)(2)D(3), mainly conjugated
      as glycoside. This study aims to validate a simple novel method of evaluation of
      the VDA of SG leaves. Aqueous extracts of SG were purified using C(18)
      minicolumns and assayed by RIA with an antibody raised in rabbits by injection of
      the acid-C22, 1alpha-(OH)Vitamin D(3). Data were expressed as glycoside
      equivalent to 1,25-(OH)(2)D(3) in ng/g of dry leaves. We compared this data with
      1,25-(OH)(2)D(3) levels measured, in the same samples, by liquid chromatography
      (HPLC) after enzyme cleavage. This procedure involved the incubation of SG leaves
      with rumen fluid, followed by C(18)-OH solid phase extraction. The 1,25
      (OH)(2)D(3) fraction was run by HPLC and detection was achieved using a
      photodiode array detector. Data were expressed as micrograms of 1,25
      (OH)(2)D(3)/g dry leaves. A significant regression of 1,25-(OH)(2)D(3) levels (Y)
      as a function of glycoside RIA 1,25-(OH)(2)D(3) equivalents (X) was found:
      Y=12.02+0.35X [R=0.81; P=0,0002; N=15], allowing us to conclude that this novel
      assay could be used to estimate the amount of this active principle contained in
      SG leaves.

PMID- 17223549
TI  - Vitamin D in the treatment of pulmonary tuberculosis.
AB  - Vitamin D was used to treat tuberculosis in the pre-antibiotic era. New insights
      into the immunomodulatory properties of 1alpha,25-dihydroxy-vitamin D have
      rekindled interest in vitamin D as an adjunct to antituberculous therapy. We
      describe the historical use of vitamin D in tuberculosis treatment; discuss the
      mechanisms by which it may modulate host response to infection with Mycobacterium
      tuberculosis; and review three clinical trials and ten case series in which
      vitamin D has been used in the treatment of pulmonary tuberculosis.

PMID- 17223550
TI  - Parathyroid hormone stimulation of the renal 25-hydroxyvitamin D-1alpha
      hydroxylase--effect of age and free radicals.
AB  - The capacity of parathyroid hormone (PTH) to increase serum 1,25(OH)(2)D levels
      declines with age in both rats and humans. In young rats, PTH stimulates renal
      1,25(OH)(2)D production and increases mRNA levels for the terminal mitochondrial
      P450 of the 1alpha-hydroxylase complex (CYP27B1 or CYP1alpha). However, in older
      rats PTH increases mRNA levels but not 1,25(OH)(2)D production. This suggests
      that in old animals there is either decreased CYP1alpha protein levels in
      response to PTH or that the protein produced lacks functionality. The CYP1alpha
      protein is located on the inner mitochondrial membrane, the site of increased
      free radical production with age. To study these possibilities, we examined the
      effect of PTH and free radicals on CYP1alpha expression in a model system-AOK-B50
      renal tubular cells. PTH increased CYP1alpha mRNA and protein in a similar time
      dependent manner, suggesting that CYP1alpha protein levels were largely regulated
      by mRNA levels. The effect of free radicals was determined by preincubation with
      hydrogen peroxide (H(2)O(2)), a standard model for studying free radical damage.
      H(2)O(2) inhibited PTH-stimulated CYP1alpha protein levels and 1,25(OH)(2)D
      production in a dose dependent manner. However, 1,25(OH)(2)D production was more
      sensitive to H(2)O(2) than was CYP1alpha protein levels. This suggests that the
      catalytic activity of the CYP1alpha protein may be reduced by free radical damage
      in these cells. Future studies will focus on detecting oxidative damage in this
      model system and in vivo.

PMID- 17223552
TI  - Caffeine decreases vitamin D receptor protein expression and 1,25(OH)2D3
      stimulated alkaline phosphatase activity in human osteoblast cells.
AB  - Of the various risk factors contributing to osteoporosis, dietary/lifestyle
      factors are important. In a clinical study we reported that women with caffeine
      intakes >300 mg/day had higher bone loss and women with vitamin D receptor (VDR)
      variant, tt were at a greater risk for this deleterious effect of caffeine.
      However, the mechanism of how caffeine effects bone metabolism is not clear. 1,25
      Dihydroxy vitamin D(3) (1,25(OH)(2)D(3)) plays a critical role in regulating bone
      metabolism. The receptor for 1,25(OH)(2)D(3), VDR has been demonstrated in
      osteoblast cells and it belongs to the superfamily of nuclear hormone receptors.
      To understand the molecular mechanism of the role of caffeine in relation to
      bone, we tested the effect of caffeine on VDR expression and 1,25(OH)(2)D(3)
      mediated actions in bone. We therefore examined the effect of different doses of
      caffeine (0.2, 0.5, 1.0 and 10mM) on 1,25(OH)(2)D(3) induced VDR protein
      expression in human osteoblast cells. We also tested the effect of different
      doses of caffeine on 1,25(OH)(2)D(3) induced alkaline phosphatase (ALP) activity,
      a widely used marker of osteoblastic activity. Caffeine dose dependently
      decreased the 1,25(OH)(2)D(3) induced VDR expression and at concentrations of 1
      and 10mM, VDR expression was decreased by about 50-70%, respectively. In
      addition, the 1,25(OH)(2)D(3) induced alkaline phosphatase activity was also
      reduced at similar doses thus affecting the osteoblastic function. The basal ALP
      activity was not affected with increasing doses of caffeine. Overall, our results
      suggest that caffeine affects 1,25(OH)(2)D(3) stimulated VDR protein expression
      and 1,25(OH)(2)D(3) mediated actions in human osteoblast cells.

PMID- 17223551
TI  - Serum 25(OH)D levels, dietary intake of vitamin D, and colorectal adenoma
      recurrence.
AB  - There is strong epidemiological and laboratory evidence that vitamin D may be
      protective against colorectal neoplasia. Therefore, we sought to assess the
      relationship between serum 25(OH)D levels, dietary intake of vitamin D, and
      colorectal adenoma recurrence in our ursodeoxycholic acid trial. A total of 568
      participants were randomly selected for analysis of serum 25(OH)D levels. The
      range of total 25(OH)D was 5.5-66.1 ng/ml, with a median of 25.6 ng/ml. After
      categorizing 25(OH)D levels into tertiles based on the population distribution,
      the adjusted odds ratios (95% CI) for adenoma recurrence in the second and third
      tertiles were 0.88 (0.56-1.39) and 0.78 (0.49-1.24), respectively. The
      association between serum 25(OH)D and adenoma recurrence appeared to be stronger
      among women than men. As compared to those below the median value, women with
      serum 25(OH)D levels above the median had an OR (95% CI) of 0.59 (0.30-1.16); the
      corresponding OR (95% CI) for men was 0.95 (0.60-1.49). Analyses by dietary
      vitamin D intake revealed no statistically significant associations. In summary,
      the results of this study show a moderate, nonsignificant inverse association
      between serum 25(OH)D levels and reduced risk for colorectal adenoma recurrence,
      particularly among women.

PMID- 17223553
TI  - In vivo relevance for photoprotection by the vitamin D rapid response pathway.
AB  - Vitamin D is produced by exposure of 7-dehydrocholesterol in the skin to UV
      irradiation (UVR) and further converted in the skin to the biologically active
      metabolite, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) and other compounds. UVR
      also results in DNA damage producing cyclobutane pyrimidine dimers (CPD). We
      previously reported that 1,25(OH)(2)D(3) at picomolar concentrations, protects
      human skin cells from UVR-induced apoptosis, and decreases CPD in surviving
      cells. 1,25(OH)(2)D(3) has been shown to generate biological responses via two
      pathways-the classical steroid receptor/genomic pathway or a rapid, non-genomic
      pathway mediated by a putative membrane receptor. Whether the rapid response
      pathway is physiologically relevant is unclear. A cis-locked, rapid-acting
      agonist 1,25(OH)(2)lumisterol(3) (JN), entirely mimicked the actions of
      1,25(OH)(2)D(3) to reduce fibroblast and keratinocyte loss and CPD damage after
      UVR. The effects of 1,25(OH)(2)D(3) were abolished by a rapid-acting antagonist,
      but not by a genomic antagonist. Skh:hr1 mice exposed to three times the minimal
      erythemal dose of solar-simulated UVR and treated topically with 1,25(OH)(2)D(3)
      or JN immediately after UVR showed reduction in UVR-induced UVR-induced sunburn
      cells (p<0.01 and <0.05, respectively), CPD (p<0.01 for both) and
      immunosuppression (p<0.001 for both) compared with vehicle-treated mice. These
      results show for the first time an in vivo biological response mediated by a
      rapid-acting analog of the vitamin D system. The data support the hypothesis that
      1,25(OH)(2)D(3) exerts its photoprotective effects via the rapid pathway and
      raise the possibility that other D compounds produced in skin may contribute to
      the photoprotective effects.

PMID- 17223554
TI  - Creative synthesis of novel vitamin D analogs for health and disease.
AB  - We report new analogs of 1alpha,25-dihydroxyvitamin D(3) (1) in three categories.
      First, design and synthesis of ligands for a mutant vitamin D receptor
      (VDR)(Arg274Leu), which possess proper functional groups at both C1alpha and
      C2alpha positions of 1 to study the biological activity of the mutant VDR. Among
      our synthetic analogs, 1alpha-methyl-2alpha-(3-hydroxypropyl)-25-hydroxyvitamin
      D(3) (8) showed 7.3-fold greater transcriptional activity for the VDR(Arg274Leu)
      than that of 1. Next, we examined the antiproliferative activity of 2-substituted
      19-norvitamin D(3) analogs on an immortalized normal prostate cell line, PZ-HPV
      7, and we found MART 10 (14) showed the activity even at very low concentration
      of 10(-10) to 10(-11)M. We also synthesized 25-hydroxy-19-norvitamin D(3) (13)
      using Julia-type olefination to connect between the C5 and C6 positions,
      effectively, to test it as a prohormone type agent for antiprostate diseases.
      Synthesized compound 13 showed potent antiproliferative activity in PZ-HPV-7,
      which has high 1alpha-hydroxylase activity. Finally, we describe design and
      synthesis of a new TEI-9647 analog, 2alpha-(3-hydroxypropoxy)-24-propyl-25
      dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactone (17), which showed the strongest
      VDR antagonism. Its IC(50) value is 7.4pM to inhibit differentiation of HL-60
      cells induced by 10nM of 1.

PMID- 17223555
TI  - Steam pretreatment of H(2)SO(4)-impregnated Salix for the production of
      bioethanol.
AB  - In the bioconversion of lignocellulosic materials to ethanol, pretreatment of the
      material prior to enzymatic hydrolysis is essential to obtain high overall yields
      of sugar and ethanol. In this study, steam pretreatment of fast-growing Salix
      impregnated with sulfuric acid has been investigated by varying the temperature
      (180-210 degrees C), the residence time (4, 8 or 12 min), and the acid
      concentration (0.25% or 0.5% (w/w) H(2)SO(4)). High sugar recoveries were
      obtained after pretreatment, and the highest yields of glucose and xylose after
      the subsequent enzymatic hydrolysis step were 92% and 86% of the theoretical,
      respectively, based on the glucan and xylan contents of the raw material. The
      most favorable pretreatment conditions regarding the overall sugar yield were 200
      degrees C for either 4 or 8 min using 0.5% sulfuric acid, both resulting in a
      total of 55.6g glucose and xylose per 100g dry raw material. Simultaneous
      saccharification and fermentation experiments were performed on the pretreated
      slurries at an initial water-insoluble content of 5%, using ordinary baker's
      yeast. An overall theoretical ethanol yield of 79%, based on the glucan and
      mannan content in the raw material, was obtained.

PMID- 17223556
TI  - Copper(II) and lead(II) sorption from aqueous solution by non-living Spirogyra
      neglecta.
AB  - Dried biomass of Spirogyra neglecta rapidly sorbed the test metals and the
      process became saturated in 10-20min. Maximum sorption of Pb(II) [116.1mgg(-1)]
      and Cu(II) [115.3mgg(-1)] occurred at 0.1gl(-1) biomass and 100mgl(-1) metal
      concentration in the solution. Sorption of Cu(II) and Pb(II) occurred optimally
      at pH 4.5 and 5.0, respectively. Lead(II) and Cu(II) sorption were lesser from
      binary metal solution than from single metal solution. Lead(II) more severely
      inhibited Cu(II) sorption than vice versa thus reflecting greater affinity of
      Pb(II) for the biomass. NaOH pretreatment slightly enhanced the metal removal
      ability of the biomass. During repeated sorption/desorption cycles, Pb(II) and
      Cu(II) sorption decreased by 11% and 27%, respectively, at the end of the fifth
      cycle due inter alia to 10-15% loss of biomass. Nevertheless, Spirogyra appears
      to be a good sorbent for removing metals Cu(II) and Pb(II) from wastewaters.

PMID- 17223557
TI  - A comparison of the performance of mesophilic and thermophilic anaerobic filters
      treating papermill wastewater.
AB  - Two anaerobic filters, one mesophilic (35 degrees C) and one thermophilic (55
      degrees C), were operated with a papermill wastewater at a series of organic
      loadings. The hydraulic retention time (HRT) ranged from 6 to 24 h with organic
      loading rates (OLR) 1.07-12.25 g/l per day. At loading rates up to 8.4 g COD/l d,
      there was no difference in terms of the removal of soluble COD (SCOD) and gas
      production. At the higher organic loading rate, the SCOD removal performance of
      thermophilic digester was slightly better compare to mesophilic digester. Similar
      trend was also observed in terms of the daily methane production. The stability
      of thermophilic digester was also better than mesophilic digester particularly
      for the higher organic loadings. Volatile fatty acid accumulation was observed in
      the effluent of the mesophilic filter at the higher organic loading rates. The
      Stover-Kincannon model was applied to both digesters and it was found that model
      was applicable to both digesters for papermill wastewater. K(B) and U(max)
      constants from the Stover-Kincannon model were also derived.

PMID- 17223558
TI  - Citric acid production by a novel Aspergillus niger isolate: I. Mutagenesis and
      cost reduction studies.
AB  - Ultraviolet-irradiation (UV), ethyl methane sulfonate (EMS) and acridine orange
      (AO) were used to induce citric acid overproduction mutations in Aspergillus
      niger UMIP 2564. Among 15, eight of the mutant derivatives, were improved with
      respect to citric acid production from sucrose in batch cultures. Maximum product
      yield (60.25%) was recorded by W5, a stable UV mutant, with approximately 3.2
      fold increase when compared to the parental wild type strain. In terms of the
      kinetic parameters for batch fermentation processes, the mutation doubled the
      specific substrate uptake rate and achieved 4.5- and 7.5-fold improvements in
      citric acid productivity and specific productivity, respectively. For reduction
      of the fermentation medium cost, corn steep liquor and calcium phosphate pre
      treated beet molasses were successfully used as substituents of nitrogen and
      carbon sources in the growth medium, respectively. These medium substitutions
      resulted in a W5 citric acid fermentation culture with a product yield of 74.56%.

PMID- 17223559
TI  - Production of feather protein hydrolysate by keratinolytic bacterium Vibrio sp.
      kr2.
AB  - A feather protein hydrolysate was produced using the keratinolytic bacterium
      Vibrio sp. strain kr2. Complete feather degradation was observed in medium
      containing up to 60 g L(-1) raw feathers. Cultivation on 40, 60 or 80 g L(-1)
      feathers for five days resulted in similar amounts of soluble protein, reaching
      maximum values around 2.5 g L(-1). Maximum yields of soluble protein were
      achieved at 30 degrees C and initial pH ranging from 6.0 to 8.0. Strain kr2 was
      effective in producing keratin hydrolysate from chicken feathers. Bacterial
      feather hydrolysate has the potential for utilization as an ingredient in animal
      feed or as organic fertilizer, thereby reducing the environmental impact of
      feather waste from the poultry industry.

PMID- 17223560
TI  - Intensive care unit management of fever following traumatic brain injury.
AB  - Fever, in the presence of traumatic brain injury (TBI), is associated with
      worsened neurologic outcomes. Studies prior to the publication of management
      guidelines revealed an undertreatment of fever in patients with neurologic
      insults. Presently the adult TBI guidelines state that maintenance of
      normothermia should be a standard of care therefore improvement in management of
      fever in these patients would be expected. The specific aims of the study were
      to: (1) determine the incidence of fever (T>or=38.5 degrees C) in a population of
      critically ill patients with TBI; (2) describe what interventions were recorded
      by intensive care unit (ICU) nurses in managing fever; (3) ascertain the rate of
      adherence with published normothermia guidelines. Medical record review of
      available hospital records was conducted on patients admitted to a level I trauma
      center following severe TBI (N=108) from the parent study. Temperature data was
      abstracted and contemporaneous nursing documentation was examined for evidence of
      intervention for fever and adherence with published standards. Data analyses were
      performed that included descriptive statistics. Seventy-nine percent of TBI
      patients (85/108) had at least one recorded fever event while in the ICU. However
      in only 31% of events did the patient receive any documented intervention by
      nursing staff for the elevated temperature. The most frequently documented
      intervention was pharmacologic (358/1166 elevations). Other nursing actions (e.g.
      use of fan) accounted for a minority (<1%) of nursing interventions documented.
      Patients were more likely to have a high temperature that exceeded 40 degrees C
      (13%) than a temperature that was normothermic (5%). There continues to be an
      under treatment of fever in patients with TBI by critical care nurses despite our
      knowledge of its negative effects on outcomes. There remains a gap in translation
      between patient outcomes research and bedside practice that needs to be overcome,
      thus research efforts need to now focus on understanding nurses' decision-making
      processes and the best methods of fever reduction in patients with TBI.

PMID- 17223561
TI  - Predicting the outcome of shunt surgery in normal pressure hydrocephalus.
AB  - We studied retrospectively the effectiveness of the repeated lumbar CSF tap test
      (RTT), lumbar external CSF drainage (LED) and radioisotope cisternography (RIC)
      in predicting the outcome of shunt surgery, as well as the diagnostic and
      prognostic value of periventricular hyperintensity (PVH) and of the classic
      clinical triad in normal pressure hydrocephalus. Two hundred and seventy patients
      were referred to the Departments of Neurosurgery, in Nancy, France and in
      Istanbul, Turkey. The decision to perform surgery was based on the clinical
      presentation (all patients had at least two symptoms of the classic clinical
      triad), neuroimaging examinations and the results of the RTT (taps were performed
      on three consecutive days and at each tap a minimum of 30 to 40 cc of CSF was
      removed), the LED (drainage was performed for 3 days and the volume of CSF
      drained daily was a minimum of 150 to 250 cc) or the RIC. After all shunt
      procedures, postoperative assessments verified improvements in 88% of the RTT
      group, 91% of the LED group and 66% of the RIC group. Gait disturbance had
      improved in 90% at the end of the second and twelfth month follow-up. Cognitive
      dysfunction had improved in 79% at the second and in 77% at the twelfth month
      follow-up. Urinary incontinence had improved in 66% at the second and in 62% at
      the twelfth month follow-up. From the surgical point of view, the greatest
      difficulty is not to make the diagnosis, but rather to identify the appropriate
      patients to operate on. The decision to perform shunt surgery should be based on
      strict clinical findings associated with CT and MRI criteria and especially with
      positive RTT or LED test results.

PMID- 17223562
TI  - Synthesis and biological evaluation of new N-(2-hydroxy-4(or 5)
      nitro/aminophenyl)benzamides and phenylacetamides as antimicrobial agents.
AB  - A new series of N-(2-hydroxy-4(or 5)-nitro/aminophenyl)benzamide and
      phenylacetamide derivatives (1a-1n, 2a-2n) were synthesized and evaluated for
      antibacterial and antifungal activities against Staphylococcus aureus, Bacillus
      subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli,
      Candida albicans, and their drug-resistant isolate. Microbiological results
      indicated that the compounds possessed a broad spectrum of activity against the
      tested microorganisms at MIC values between 500 and 1.95 microg/ml. Benzamide
      derivative 1d exhibited the greatest activity with MIC values of 1.95, 3.9, and
      7.8 microg/ml against drug-resistant B. subtilis, B. subtilis, and S. aureus,
      respectively.

PMID- 17223564
TI  - Consideration of the three-dimensional structure of core shells (capsids) in
      spherical retroviruses.
AB  - The problem of three-dimensional organization of retroviral cores has been a
      matter of interest for the past 30 years. The general opinion in favor of
      icosahedral symmetry based on electron microscopy observations was questioned
      when cryo-electron microscopy failed to provide convincing evidence in its favor.
      More recent studies by cryo-electron microscopy, X-ray crystallography and in
      vitro assembly of the CA domain of Human immuno deficiency virus (HIV), Murine
      leukemia virus (MuLV) and Rous sarcoma virus (RSV) threw new light on the
      organization of retroviral cores. In this communication we report how we produced
      a three-dimensional (3D) model of MuLV core using data from CA assembly on a
      lipid film [Ganser, B.K., Cheng, A., Sundquist, W.I., Yeager, M., 2003. Three
      dimensional structure of the M-MuLV CA protein on a lipid monolayer: a general
      model for retroviral capsid assembly. EMBO J. 22, 2886-2892]. The resulting
      structure revealed that the molecular organization of the core shell is specific
      and the presence of a 5,3,2 rotational symmetry of the 3D model provides support
      for icosahedral shape of MuLV cores. The model made it possible to determine the
      diameter of the cores and calculate the number of CA copies as well as the
      molecular mass of a core of specific diameter. Thus MuLV cores 68 (or 81.6) nm in
      diameter consist of 1500 (or 2160) copies of CA. About 12% of molecules from
      fullerene-like Gag shells versus 71% of molecules of closely packed (core-like).
      Gag shells were not incorporated into the core shells (capsids). Our 3D models
      received support from X-ray data of MuLV CA NTD domain published by Mortuza et
      al. [Mortuza, G., Haire, L.F., Stevens, A., Smerdon, S.J., Stoye, J.P., Taylor,
      I.A., 2004. High resolution structure of a retroviral capsid hexameric amino
      terminal domain. Nature 431, 481-485].

PMID- 17223563
TI  - Analysis of living cells grown on different titanium surfaces by time-lapse
      confocal microscopy.
AB  - In this study we have combined fluorescence- and reflection-confocal laser
      scanning microscopy for the simultaneous visualization of living cells and
      surface topography beneath them. To this purpose we have designed a specific flow
      chamber and we have tested it with osteoblasts grown on an opaque, thick support,
      made of smooth or sandblasted titanium. Cells were loaded with Calcein-AM or
      tetramethylrhodamine methyl ester (TMRM), two probes employed as indicators of
      cell viability/morphology and mitochondrial membrane potential, respectively.
      Besides the acquisition of stacks of confocal sections, the system allowed also
      vertical views and faithful three-dimensional reconstruction of the samples.
      Confocal microscope implemented with our flow chamber proved to be a promising
      tool for time-lapse investigation of cell-biomaterial interactions.

PMID- 17223565
TI  - Is there a role for therapeutic lobectomy for emphysema?
AB  - OBJECTIVE: The feasibility of performing a standard lobectomy in patients with
      non-small cell lung cancer (NSCLC) and severe heterogeneous emphysema whose
      respiratory reserve is outside standard operability guidelines has been described
      [Edwards JG, Duthie DJR, Waller DA. Lobar volume reduction surgery: a method of
      increasing the lung cancer resection rate in patients with emphysema. Thorax
      2001;56:791-5; Korst RJ, Ginsberg RJ, Ailawadi M, Bains MS, Downey RJ, Rusch V,
      Stover D. Lobectomy improves ventilatory function in selected patients with
      severe COPD. Ann Thorac Surg 1998;66:898-902; Carretta A, Zannini P, Puglisi A,
      Chiesa G, Vanzulli A, Bianchi A, Fumagalli A, Bianco S. Improvement in pulmonary
      function after lobectomy for non-small cell lung cancer in emphysematous
      patients. Eur J Cardiothorac Surg 1999;15(5):602-7]. Postoperative lung function
      was better than predicted, attributable to the therapeutic benefit of deflation
      of the hemithorax. Our aim was to determine whether the physiological benefits of
      this approach were superior to conventional non-anatomical lung volume reduction
      surgery (LVRS) in similar patients. METHODS: A retrospective review of a single
      surgeon's experience identified 34 consecutive patients who underwent upper
      lobectomy for completely resected stage I-II NSCLC, and who had severe
      heterogeneous emphysema of apical distribution with a predicted postoperative
      FEV1 of less than 40%. Their perioperative characteristics, postoperative
      spirometry and survival of these cases were compared to 46 similar patients who
      underwent unilateral upper lobe LVRS during the same period. RESULTS: Data
      expressed as median (range). LVRS patients were significantly younger (59 years
      [39-70] vs 67 years [48-79] p<0.001), with more severe airflow obstruction
      (FEV(1) %pred 24 [12-60] vs 44 [17-54] p<0.001) and more heterogenous disease
      ('Q' score 4 [0.5-11.5] vs 7 [1-13] p=0.001) than the lobectomy group. No
      significant difference was found in median survival (88 vs 53 months, p=0.06).
      Lobectomy patients had a shorter air leak duration (5 days [2-36] vs 9 days [1
      40], p=0.02) and hospital stay (8 days [3-63] vs 13 days [6-90] p=0.01). A
      significant correlation was found between pre-operative Q score and percentage
      improvement in FEV1 (r=-0.33, p=0.02). CONCLUSIONS: Lobectomy for lung cancer in
      patients in severe heterogenous chronic obstructive pulmonary disease is
      associated with similar improvement in airflow obstruction as conventional LVRS,
      but is associated with a shorter postoperative course. Lobectomy may therefore
      offer a therapeutic alternative to conventional LVRS in a selected population.

PMID- 17223567
TI  - Septal-lateral annnular cinching perturbs basal left ventricular transmural
      strains.
AB  - OBJECTIVE: Septal-lateral annular cinching ('SLAC') corrects both acute and
      chronic ischemic mitral regurgitation in animal experiments, which has led to the
      development of therapeutic surgical and interventional strategies incorporating
      this concept (e.g., Edwards GeoForm ring, Myocor Coapsys, Ample Medical PS3).
      Changes in left ventricular (LV) transmural cardiac and fiber-sheet strains after
      SLAC, however, remain unknown. METHODS: Eight normal sheep hearts had two triads
      of transmural radiopaque bead columns inserted adjacent to (anterobasal) and
      remote from (midlateral equatorial) the mitral annulus. Under acute, open chest
      conditions, 4D bead coordinates were obtained using videofluoroscopy before and
      after SLAC. Transmural systolic strains were calculated from bead displacements
      relative to local circumferential, longitudinal, and radial cardiac axes.
      Transmural cardiac strains were transformed into fiber-sheet coordinates (X(f),
      X(s), X(n)) oriented along the fiber (f), sheet (s), and sheet-normal (n) axes
      using fiber (alpha) and sheet (beta) angle measurements. RESULTS: SLAC markedly
      reduced (approximately 60%) septal-lateral annular diameter at both end-diastole
      (ED) (2.5+/-0.3 to 1.0+/-0.3 cm, p=0.001) and end-systole (ES) (2.4+/-0.4 to
      1.0+/-0.3 cm, p=0.001). In the LV wall remote from the mitral annulus, transmural
      systolic strains did not change. In the anterobasal region adjacent to the mitral
      annulus, ED wall thickness increased (p=0.01) and systolic wall thickening was
      less in the epicardial (0.28+/-0.12 vs 0.20+/-0.06, p=0.05) and midwall (0.36+/
      0.24 vs 0.19+/-0.11, p=0.04) LV layers. This impaired wall thickening was due to
      decreased systolic sheet thickening (0.20+/-0.8 to 0.12+/-0.07, p=0.01) and sheet
      shear (-0.15+/-0.07 to -0.11+/-0.04, p=0.02) in the epicardium and sheet
      extension (0.21+/-0.11 to 0.10+/-0.04, p=0.03) in the midwall. Transmural
      systolic and remodeling strains in the lateral midwall (remote from the annulus)
      were unaffected. CONCLUSIONS: Although SLAC is an alluring concept to correct
      ischemic mitral regurgitation, these data suggest that extreme SLAC adversely
      effects systolic wall thickening adjacent to the mitral annulus by inhibiting
      systolic sheet thickening, sheet shear, and sheet extension. Such alterations in
      LV strains could result in unanticipated deleterious remodeling and warrant
      further investigation.

PMID- 17223566
TI  - Non-cultured cell transplantation in an ovine model of non-ischemic heart
      failure.
AB  - OBJECTIVE: Cell therapy may be a promising alternative or adjunct to current
      treatment modalities for ischemic heart failure. But little is known on the
      impact of myogenic cell transplantation in large animal models of non-ischemic
      cardiomyopathy. The aim of the present study was to explore whether an ovine
      model of toxin-induced heart disease could benefit from non-cultured skeletal
      muscle cell transplantation. METHODS: Sequential intracoronary injections of
      doxorubicin (0.75 mg/kg) were carried out every 2 weeks until echocardiographic
      detection of myocardial dysfunction. Sheep were then randomly assigned to either
      non-cultured cell transplantation (n=8) or placebo injection (n=5). For the cell
      therapy group, a skeletal muscle biopsy (about 10 g) was explanted from each
      animal approximately 3h before grafting. After thoracotomy, 20 epicardial
      injections were carried out. The animals were assessed one last time before
      sacrifice, 2 months after the thoracotomy. Cells were tracked with cmDiI (red
      fluorescence) and characterized with immunohistochemistry with monoclonal
      antibodies to a fast skeletal isoform of myosin heavy chain. RESULTS: Two months
      after intramyocardial grafting, tissue Doppler imaging and conventional
      echocardiographic assessment of the groups showed a marked improvement in the non
      cultured cell therapy group. Ejection fraction (EF) (p<0.05) as well as systolic
      endocardial velocities (p<0.01) improved versus the placebo group. CmDiI and
      skeletal myosin heavy chain expression was detected in all animals at 2 months
      after implantation confirming engraftment of skeletal muscle cells. CONCLUSIONS:
      In conclusion, our data indicate that non-cultured muscle cell transplantation is
      feasible and may translate into a functional benefit in an ovine model of dilated
      heart failure.

PMID- 17223568
TI  - Arterial switch operation in patients with Taussig-Bing anomaly--influence of
      staged repair and coronary anatomy on outcome.
AB  - OBJECTIVE: This study evaluated the results of arterial switch operation and
      closure of ventricular defects (ASO+VSDc) for double outlet right ventricle with
      sub-pulmonary ventricular septal defect (Taussig-Bing anomaly). METHODS: Between
      1988 and 2003, 33 patients (25 male, 76%) with Taussig-Bing anomaly underwent
      ASO+VSDc (median age 39 days, 1 day-2.1 years). The relationship of the great
      arteries was antero-posterior (Group I, n=19) or side-by-side (Group II, n=14).
      Coronary anatomy (Yacoub's classification) was exclusively type A or D in Group I
      and predominantly type D or E in Group II (64%). Incidence of sub-aortic
      obstruction and aortic arch obstruction was similar in Group I and II (37% vs
      57%, p=0.25 and 84% vs 79%, p=0.98, respectively). Twenty-five patients (76%) had
      one-stage total correction. Risk factors were analysed using multivariable
      analysis. Follow-up was complete (median interval of 6.2 years; range, 0.6-15.2
      years). RESULTS: There were three early (9%) and one late death. Actuarial
      survival was 88+/-6% at 1 and 10 years. There were two early and four late re
      operations. Freedom from re-operation was 90+/-5% and 75+/-9% at 1 and 10 years.
      Four patients required cardiological re-interventions. Freedom from re
      intervention at 5 and 10 years was 79+/-9%. On multivariable analysis, complex
      coronary anatomy (type B and C) was a risk for early mortality (p<0.001) but all
      other anatomical variables and staged strategy did not influence early or
      actuarial survival. CONCLUSIONS: The ASO+VSDc approach can be applied to Taussig
      Bing anomaly with acceptable mortality and morbidity and it is the procedure of
      choice at our institution. Anatomical variables did not influence outcomes with
      this strategy. A staged strategy is still appropriate in complex cases.

PMID- 17223569
TI  - The price to pay: perversions in (cardio)thoracic surgical training.

PMID- 17223570
TI  - Suture and stapler granulomas: a word of caution.
AB  - Newly detected lung nodules during the postoperative follow-up course of a
      patient who has underwent pulmonary resection, is frequently a diagnostic
      dilemma. It is crucial to determine if the tumor is a recurrent tumor, a second
      primary tumor or a benign lesion. Currently, positron emission tomography seems
      to have replaced most of the invasive diagnostic interventions. In this study,
      three cases with false-positive nodules interpreted as recurrent malignancy on
      PET scans are presented. They were eventually found out to be foreign body hyper
      reaction granulomas.

PMID- 17223571
TI  - Protective effect of verapamil on multiple hepatotoxic factors-induced liver
      fibrosis in rats.
AB  - The purpose of the present work was to investigate the effect of verapamil on
      liver fibrosis induced by multiple hepatotoxic factors in rats. Male Wistar rats
      were divided into a normal control group, a liver fibrosis model control group,
      and verapamil groups with different dosages. Multiple hepatotoxic factors
      including carbon tetrachloride (CCl(4)), ethanol and high cholesterol were used
      to make the animal model of liver fibrosis. The parameters of serum l-alanine
      aminotransferase (ALT), liver malondialdehyde and hydroxyproline contents were
      measured. Samples of the liver obtained by biopsy were subjected to histological
      and immunohistochemical studies for the expressions of alpha-smooth muscle actin
      (alpha-SMA) and transforming growth factor-beta(1) (TGF-beta(1)). Results showed
      that verapamil induced a dose-dependent decrease of serum ALT, liver
      malondialdehyde and hydroxyproline compared with liver fibrosis model control.
      Verapamil reduced hepatocyte degeneration and necrosis, and delayed the formation
      of liver fibrosis. The levels of expression of alpha-SMA and TGF-beta(1) in the
      hepatic tissue of three of the verapamil-treated groups were significantly less
      than those of the liver fibrosis model control group. The results showed that
      verapamil acts against the formation of liver fibrosis, the mechanism might be
      due to a protective effect for hepatocytes and through decreasing TGF-beta(1) to
      block the activation of hepatic stellate cells (HSCs) and collagen gene
      expression.

PMID- 17223572
TI  - Thinking within the D box: initial identification of Cdh1-APC substrates in the
      nervous system.
AB  - The anaphase-promoting complex (APC) has a well-established role in cell cycle
      control, but recent exciting evidence has uncovered unexpected neurobiological
      functions for this complex E3 ubiquitin ligase. With its co-activator Cdh1, APC's
      effects upon the nervous system range from regulation of axon growth and
      patterning to development of synapses to neuronal survival. The Cdh1-APC
      substrates that control these biological processes in neurons are just beginning
      to be identified. These findings may offer a glimpse of the wide spectrum of
      neural activities that are orchestrated by Cdh1-APC.

PMID- 17223573
TI  - RB and RB2/P130 genes cooperate with extrinsic signals to promote differentiation
      of rat neural stem cells.
AB  - Mechanisms governing commitment and differentiation of the cells of the nervous
      system begin to be elucidated: how extrinsic and intrinsic components are related
      remains poorly understood. To investigate this issue, we overexpressed genes of
      the retinoblastoma (Rb) family RB and RB2/p130, which play an important role
      during nerve cell maturation, in rat neural stem cells (NSCs). Immunostaining of
      neurons, astrocytes and oligodendrocytes in cultures overexpressing pRb or
      pRb2/p130 revealed that these genes affect lineage specification of
      differentiating NSCs. We observed modifications in percentage of differentiated
      cells indicating a shift towards the phenotype induced by culture conditions.
      Results were confirmed by detection of the expression levels of differentiation
      markers by RT-PCR. Analysis of BrdU incorporation and detection of an early
      marker of apoptosis suggest that the effect of pRb and pRb2/p130 overexpression
      is not dependent on the inhibition of cell proliferation, nor does it rely on the
      regulation of cell survival. Our findings suggest that Rb family genes are
      involved in fate determination of the cells of the nervous system. However, their
      role seems subsidiary to that of the extrinsic signals that promote lineage
      specification and appear to be mediated by a direct effect on the acquisition of
      a specific phenotype.

PMID- 17223575
TI  - Critical illness VR rehabilitation device (X-VR-D): evaluation of the potential
      use for early clinical rehabilitation.
AB  - We present a new critical illness VR rehabilitation device (X-VR-D) that enables
      diversified self-training and is applicable early in the rehabilitation of
      severely injured or ill patients. The X-VR-D consists of a VR program delivering
      a virtual scene on a flat screen and simultaneously processing commands to a
      moving chair mounted on a motion system. Sitting in the moving chair and exposed
      to a virtual reality environment the device evokes anticipatory and reactive
      muscle contractions in trunk and extremities for postural control. In this study
      we tested the device in 10 healthy subjects to evaluate whether the enforced
      perturbations indeed evoke sufficient and reproducible EMG muscle activations. We
      found that particular fast roll and pitch movements evoke adequate trunk and leg
      muscle activity. Higher angular velocities and higher angles of inclination
      elicited broader EMG bursts and larger amplitudes. The muscle activation pattern
      was highly consistent between different subjects and although we found some
      habituation of EMG responses in consecutive training sessions, the general
      pattern was maintained and was predictable for specific movements. The
      habituation was characterized by more efficient muscle contractions and better
      muscle relaxation during the rest positions of the device. Furthermore we found
      that the addition of a virtual environment to the training session evoked more
      preparatory and anticipatory muscle activation than sessions without a virtual
      environment. We conclude that the X-VR-D is safe and effective to elicit
      consistent and reproducible muscle activity in trunk and leg muscles in healthy
      subjects and thus can be used as a training method.

PMID- 17223574
TI  - Analysis of aPKClambda and aPKCzeta reveals multiple and redundant functions
      during vertebrate retinogenesis.
AB  - Retinal lamination is known to depend on cell polarity and localized signaling.
      In vertebrates, atypical protein kinase C proteins, aPKClambda/iota and aPKCzeta,
      are essential for apical-basal cell polarity. However, it is not known to what
      extent functional redundancy has precluded a comprehensive functional
      characterization of aPKC signaling during vertebrate retinogenesis. Here, we show
      that aPKCs lambda and zeta are functionally redundant for multiple aspects of
      retinogenesis including mitotic division location and orientation, cell-type
      positioning, and retinal pigment epithelial (RPE) and photoreceptor cell
      morphogenesis. Genetic mosaic analyses demonstrate a cell-autonomous requirement
      of aPKCs for RPE and photoreceptor development, and a cell-non-cell-autonomous
      function that is intrinsic to the neural retina for cell-type positioning. Our
      observations uncover a previously unappreciated involvement of aPKCzeta during
      zebrafish retinogenesis and suggest that aPKC signaling primes the retinal
      environment for appropriate cell migration of post-mitotic progenitor cells but
      is not essential for correct cell-type specification.

PMID- 17223576
TI  - Reduced cortical activity during maximal bilateral contractions of the index
      finger.
AB  - The bilateral deficit refers to the phenomenon in which homologous muscles
      produce per muscle less force when contracting simultaneously than when
      contracting individually. The mechanism underlying the bilateral deficit is still
      unknown, but the most likely cause is a decline in the activation of motor units
      during bilateral contractions. In the present study, we used functional magnetic
      resonance imaging (fMRI) to measure the degree of brain activity during
      unilateral and bilateral maximal contractions in combination with force and EMG
      measurements. Subjects performed, in a semi-randomized order, maximal isometric
      contractions (MVC) with the right index finger, the left index finger and with
      both fingers simultaneously. During the task, brain activation was measured with
      a 3 T MR scanner, in combination with force and EMG recordings. The most
      important activated areas in the brain during the contractions were the
      sensorimotor cortex (precentral and postcentral gyrus), cerebellum, premotor
      cortex and supplementary motor area. During bilateral contractions, a significant
      decline in force and EMG values was found and detailed analysis of the brain
      activation data showed that this decline was accompanied with a significant
      decline in the activation of the precentral gyrus. This result suggests that the
      bilateral decline is the resultant of a decline in input to the primary motor
      area and shows that the main source of the bilateral deficit lies upstream of the
      primary motor cortex.

PMID- 17223577
TI  - Duration and not strength of activation in temporo-parietal cortex positively
      correlates with schizotypy.
AB  - Impaired self- and own body processing in patients with schizophrenia and
      individuals along the schizophrenia spectrum have been associated with
      dysfunctional cortical activation at the temporo-parietal junction. Here we
      investigated whether strength or duration of temporo-parietal junction activation
      during an own body processing task correlates with level of abnormal self
      processing in healthy subjects as measured by the frequency of spontaneously
      experienced schizotypal body schema alterations (perceptual aberrations) and
      dissociative experiences. Participants carried out a mental imagery task with
      respect to their own body. Behavioral data and high density EEG were measured.
      EEG data were analyzed using evoked potential mapping and electrical
      neuroimaging. Participants completed two validated self-report questionnaires,
      one asking about perceptual aberration and one about dissociative experiences.
      The own body transformation task activated the right temporo-parietal junction at
      310-390 ms. Participants' reaction times and duration of activation at the right
      temporo-parietal junction, but not its strength, were found to correlate
      positively with perceptual aberration scores. No relationship was found with
      dissociative experiences scores. Brain activations proceeding and following
      activation of the right temporo-parietal junction did not correlate with scores
      on either scale. The positive correlation between performance and right temporo
      parietal activation in an own body transformation task with perceptual
      aberrations scores in our healthy population suggests that disturbances in self-
      and body processing in individuals along the schizophrenia spectrum might be due
      to prolonged, rather than stronger activation of the right temporo-parietal
      junction. We argue that this might reflect local pathology, pathologies in
      cortico-cortical connections and/or re-entry of top-down processing.

PMID- 17223580
TI  - A study of idiopathic generalised epilepsy in an Irish population.
AB  - Idiopathic generalised epilepsy (IGE) is subdivided into syndromes based on
      clinical and EEG features. PURPOSE: The aim of this study was to characterise all
      cases of IGE with supportive EEG abnormalities in terms of gender differences,
      seizure types reported, IGE syndromes, family history of epilepsy and EEG
      findings. We also calculated the limited duration prevalence of IGE in our
      cohort. METHODS: Data on abnormal EEGs were collected retrospectively from two
      EEG databases at two tertiary referral centres for neurology. Clinical
      information was obtained from EEG request forms, standardised EEG questionnaires
      and medical notes of patients. RESULTS: two hundred twenty-three patients met our
      inclusion criteria, 89 (39.9%) male and 134 (60.1%) females. Tonic clonic
      seizures were the most common seizure type reported, 162 (72.65%) having a
      generalised tonic clonic seizure (GTCS) at some time. IGE with GTCS only (EGTCSA)
      was the most common syndrome in our cohort being present in 94 patients (34 male,
      60 female), with 42 (15 male, 27 female) patients diagnosed with Juvenile
      myoclonic epilepsy (JME), 23 (9 male, 14 female) with Juvenile absence epilepsy
      (JAE) and 20 (9 male, 11 female) with childhood absence epilepsy (CAE). EEG
      studies in all patients showed generalised epileptiform activity. CONCLUSIONS:
      More women than men were diagnosed with generalised epilepsy. Tonic clonic
      seizures were the most common seizure type reported. EGTCSA was the most frequent
      syndrome seen. Gender differences were evident for JAE and JME as previously
      reported and for EGTCSA, which was not reported to date, and reached statistical
      significance for EGTCA and JME.

PMID- 17223578
TI  - Sex differences in the development of neuroanatomical functional connectivity
      underlying intelligence found using Bayesian connectivity analysis.
AB  - A Bayesian method for functional connectivity analysis was adapted to investigate
      between-group differences. This method was applied in a large cohort of almost
      300 children to investigate differences in boys and girls in the relationship
      between intelligence and functional connectivity for the task of narrative
      comprehension. For boys, a greater association was shown between intelligence and
      the functional connectivity linking Broca's area to auditory processing areas,
      including Wernicke's areas and the right posterior superior temporal gyrus. For
      girls, a greater association was shown between intelligence and the functional
      connectivity linking the left posterior superior temporal gyrus to Wernicke's
      areas bilaterally. A developmental effect was also seen, with girls displaying a
      positive correlation with age in the association between intelligence and the
      functional connectivity linking the right posterior superior temporal gyrus to
      Wernicke's areas bilaterally. Our results demonstrate a sexual dimorphism in the
      relationship of functional connectivity to intelligence in children and an
      increasing reliance on inter-hemispheric connectivity in girls with age.

PMID- 17223581
TI  - Muscarinic cholinergic receptor blockade in the rat prelimbic cortex impairs the
      social transmission of food preference.
AB  - Previous findings demonstrate the involvement of the cholinergic NBM in the
      acquisition of the social transmission of food preference (STFP), a relational
      associative odor-guided learning task. There is also evidence that muscarinic
      receptors in the medial prefrontal cortex, an important NBM target area, may
      modulate olfactory associative memory. The present experiment determined the
      consequences of blocking muscarinic cholinergic receptors in a component of the
      medial prefrontal region (the prelimbic cortex) on the STFP task. Adult male
      Wistar rats were bilaterally infused with scopolamine (20 microg/site) prior to
      training and showed a severe impairment in the expression of the task measured in
      two retention sessions, both immediately and 24h after training. Local
      scopolamine injections in the prelimbic cortex did not affect other behavioral
      measures such as olfactory perception, social interaction, motivation to eat,
      neophobia, or exploration. Results suggest that muscarinic transmission in the
      prelimbic cortex is essential for the STFP, supporting the hypothesis that ACh in
      a specific prefrontal area is important for this naturalistic form of olfactory
      relational memory. Current data are discussed in the context of disruption of
      learning as a result of interferences in PLC functions such as behavioral
      flexibility, attention, and strategic planning.

PMID- 17223579
TI  - Role of hyperactive cerebellum and motor cortex in Parkinson's disease.
AB  - Previous neuroimaging studies have found hyperactivation in the cerebellum and
      motor cortex and hypoactivation in the basal ganglia in patients with Parkinson's
      disease (PD) but the relationship between the two has not been established. This
      study examined whether cerebellar and motor cortex hyperactivation is a
      compensatory mechanism for hypoactivation in the basal ganglia or is a
      pathophysiological response that is related to the signs of the disease. Using a
      BOLD contrast fMRI paradigm PD patients and healthy controls performed automatic
      and cognitively controlled thumb pressing movements. Regions of interest analysis
      quantified the BOLD activation in motor areas, and correlations between the
      hyperactive and hypoactive regions were performed, along with correlations
      between the severity of upper limb rigidity and BOLD activation. There were three
      main findings. First, the putamen, supplementary motor area (SMA) and pre-SMA
      were hypoactive in PD patients. The left and right cerebellum and the
      contralateral motor cortex were hyperactive in PD patients. Second, PD patients
      had a significant negative correlation between the BOLD activation in the
      ipsilateral cerebellum and the contralateral putamen. The correlation between the
      putamen and motor cortex was not significant. Third, the BOLD activation in the
      motor cortex was positively correlated with the severity of upper limb rigidity,
      but the BOLD activation in the cerebellum was not correlated with rigidity.
      Further, the activation in the motor cortex was not correlated with upper
      extremity bradykinesia. These findings provide new evidence supporting the
      hypothesis that hyperactivation in the ipsilateral cerebellum is a compensatory
      mechanism for the defective basal ganglia. Our findings also provide the first
      evidence from neuroimaging that hyperactivation in the contralateral primary
      motor cortex is not a compensatory response but is directly related to upper limb
      rigidity.

PMID- 17223582
TI  - Amygdala upregulation of NCAM polysialylation induced by auditory fear
      conditioning is not required for memory formation, but plays a role in fear
      extinction.
AB  - There is much interest to understand the mechanisms leading to the establishment,
      maintenance, and extinction of fear memories. The amygdala has been critically
      involved in the processing of fear memories and a number of molecular changes
      have been implicated in this brain region in relation to fear learning. Although
      neural cell adhesion molecules (NCAMs) have been hypothesized to play a role,
      information available about their contribution to fear memories is scarce. We
      investigate here whether polysialylated NCAM (PSA-NCAM) contributes to auditory
      fear conditioning in the amygdala. First, PSA-NCAM expression was evaluated in
      different amygdala nuclei after auditory fear conditioning at two different shock
      intensities. Results showed that PSA-NCAM expression was increased 24 h post
      training only in animals subjected to the highest shock intensity (1mA). Second,
      PSA-NCAM was cleaved in the basolateral amygdaloid complex through micro
      infusions of the enzyme endoneuraminidase N, and the consequences of such
      treatment were investigated on the acquisition, consolidation, remote memory
      expression, and extinction of conditioned fear memories. Intra-amygdaloid
      cleavage of PSA-NCAM did not affect acquisition, consolidation or expression of
      remote fear memories. However, intra-amygdaloid PSA-NCAM cleavage enhanced fear
      extinction processes. These results suggest that upregulation of PSA-NCAM is a
      correlate of fear conditioning that is not necessary for the establishment of
      fear memory in the amygdala, but participates in mechanisms precluding fear
      extinction. These findings point out PSA-NCAM as a potential target for the
      treatment of psychopathologies that involve impairment in fear extinction.

PMID- 17223583
TI  - Isolation and culturing of a most common anaerobic ciliate, Metopus sp.
AB  - The study includes isolation of anaerobic ciliate, Metopus sp. from an anaerobic
      reactor and development of its monoculture under laboratory conditions.
      Separation by centrifugation followed by micromanipulatory isolation resulted in
      obtaining pure Metopus culture with less bacterial contamination. The isolated
      Metopus sp. had the mean dimensions of 32 x 123 microm with the generation time
      of 53 h. Among the different basal media tried, the ciliate mineral medium (CMV)
      with 1% wheat powder suspension was the most suitable one for Metopus growth. The
      temperature and pH ranges, for the best growth of Metopus, were 30-35 degrees C
      and 6-7, respectively. Higher concentrations of volatile fatty acids (VFA) such
      as acetate, butyrate and propionate had adverse effect on Metopus growth and
      prevented its growth beyond 0.05 M concentration. Maximum COD removal was in CMV
      medium by the growth of anaerobic Metopus sp.

PMID- 17223584
TI  - Histopathologic changes in oral mucosa of Yemenis addicted to water-pipe and
      cigarette smoking in addition to takhzeen al-qat.
AB  - BACKGROUND: Because the clinicopathologic effects of takhzeen al-qat are similar
      to those induced by smoking, the aim of this paper was to study the oral effect
      of 3 bad oral habits: takhzeen al-qat and cigarette and water-pipe smoking. STUDY
      DESIGN: This study was done on 33 Yemeni chronic qat users grouped as heavy
      cigarette smokers (GI), nonsmokers (GII) and water-pipe smokers (GIII). In all
      cases (n = 33) 2 biopsies were taken (n = 66), one from the buccal mucosa at the
      chewing side and the other from a similar mucosa at the contralateral
      (nonexposed) side. Biopsies were prepared for routine H&E staining. RESULTS:
      Acanthosis appeared in 88% and 0%, abnormal rete ridges in 70% and 3%,
      hyperparakeratosis in 67% and 0%, and epithelial dysplasia in 30% and 0% of the
      chewing and nonchewing sides, respectively, in the 3 groups. Epithelial dysplasia
      appeared in 41% of GI and GIII (smokers) but in only 9% of GII (nonsmokers).
      CONCLUSIONS: Takhzeen al-qat causes distinct histopathologic changes in the oral
      mucosa at the side of chewing, such as acanthosis, abnormal rete ridges, and
      hyperparakeratosis. The association between takhzeen al-qat and cigarette or
      water-pipe smoking may increase the risk of epithelial dysplasia.

PMID- 17223585
TI  - Osteogenesis imperfecta.
AB  - Osteogenesis imperfecta is a relatively common hereditary connective tissue
      disorder characterized by bone fragility and fractures. Other frequently affected
      tissues include tendons, ligaments, skin, sclera, teeth, and middle and inner
      ear. Molecular studies have demonstrated that most cases result from mutations
      affecting the genes responsible for the formation of type 1 collagen. The
      phenotypic presentation varies from mild to lethal. Commonly observed dental
      abnormalities include dentinogenesis imperfecta and malocclusion. Medical
      therapies using bisphosphonates have resulted in reduced fracture risk and
      decreased bone pain. To date, no cases of bisphosphonate-associated osteonecrosis
      have been reported. With appropriate precautions, the patient with osteogenesis
      imperfecta can tolerate and benefit from the delivery of necessary dental care to
      control oral disease, improve function, and improve esthetics.

PMID- 17223586
TI  - Peripheral granular cell odontogenic fibroma.
AB  - Peripheral odontogenic fibroma is a rare lesion that arises on the gingiva and
      can clinically mimic a variety of reactive lesions, benign neoplasms, and
      metastases. We describe a symptomatic lesion arising on the mandibular gingiva of
      a 58-year-old female with no history of trauma or dental disease in the area. An
      excisional biopsy showed the lesional stroma to contain numerous polyhedral
      granular cells with occasional interspersed islands of inactive odontogenic
      epithelium. We believe this to represent the fourth case of peripheral granular
      cell odontogenic fibroma to be reported in detail in the literature.

PMID- 17223588
TI  - Coexistence of salivary gland cysticercosis with squamous cell carcinoma of the
      mandible.
AB  - Cysticercosis is a parasitic infestation caused by the pork tapeworm larval
      stage, Cysticercus cellulosae. The majority of the cases present in ocular,
      cerebral, and subcutaneous locations. We report the presence of cysticercosis
      inside the submandibular gland in association with squamous cell carcinoma of the
      inferior alveolar ramus of the mandible. To the best of our knowledge, this is
      the first case report documenting cysticercosis inside a salivary gland. A 65
      year-old male presented with complaints of an ulcerative lesion on the inferior
      alveolar ramus present for 2 months. Histological examination revealed a
      keratinizing well-differentiated squamous cell carcinoma involving the alveolar
      margin and mandible. The histopathological examination of the submandibular gland
      revealed cysticercosis. This case emphasizes the importance of adequate sampling
      of all the tissues obtained for associated infectious disorders, more so in
      immunosuppressed patients, which will help the clinician to manage the case
      appropriately.

PMID- 17223587
TI  - The oral mucosa in paucibacillary leprosy: a clinical and histopathological
      study.
AB  - BACKGROUND: Involvement of the oral mucosa can occur in lepromatous leprosy;
      however, lesions in the oral mucosa of paucibacillary patients have not been
      previously observed. OBJECTIVE: The objective of this study is to determine
      whether clinical and subclinical lesions exist in oral mucosa in nontreated
      paucibacillary leprosy patients, using clinical and histopathological
      examination. MATERIALS AND METHODS: A clinical and histopathological study
      involving 30 untreated paucibacillary leprosy patients was conducted. All
      patients underwent biopsies of the buccal mucosa, soft palate, and tongue. When
      acid-fast bacilli in association with inflammatory infiltrate, granulomatous or
      not, were encountered, it was considered "specific" involvement of the oral
      mucosa; and "nonspecific" involvement when the bacilli were not encountered.
      RESULTS: Eight nonspecific chronic inflammatory reactions and 1 granulomatous
      inflammatory process without acid-fast bacilli were detected. CONCLUSIONS:
      Paucibacillary leprosy patients do not exhibit specific, clinical or subclinical,
      involvement in the oral mucosa; nonspecific alterations occur even in the absence
      of signs and symptoms.

PMID- 17223589
TI  - Detection of a second mesiobuccal canal in the mesiobuccal roots of maxillary
      first molar teeth.
AB  - OBJECTIVE: The aim of the present study was to determine whether the MB2 canal in
      the mesiobuccal root (MBR) of maxillary first molars could be identified through
      a clinical access cavity preparation, with and without magnification. STUDY
      DESIGN: One hundred extracted maxillary first molar teeth were collected. After a
      clinical access cavity preparation with careful use of bur to locate any
      additional canal (dentine troughing), the MB2 canals were located in 2 stages.
      Stage I was located with unaided vision and stage II was located under moderate
      magnification with x3.5 magnifying dental loupes. All specimens were stained,
      rendered transparent, and then classified. The number of canals detected by stage
      was analyzed statistically by a chi-square test. Statistical significance was
      considered to be P < or = .05. RESULTS: Under magnification, the number of
      detected MB2 canals was increased from 55 (56.7%) to 61 (62.9%) teeth. Cleared
      teeth showed 77.32% of MB2 canals. The effectiveness of MB2 location was 73.3%
      and 82.7% in stage I and stage II, respectively. There was no statistically
      significant difference between the 2 methods of detecting the MB2 canal (P = .3).
      CONCLUSIONS: The use of magnification enhanced the ability to detect the MB2
      canals, although the difference was not statistically significant. The MB2 canals
      could not be detected in 16.5% of the teeth, mainly because of pulpal
      calcification.

PMID- 17223590
TI  - The antimicrobial effects of root canal irrigation and medication.
AB  - The role of microorganisms in the development and maintenance of pulpal and
      periapical inflammation have been well documented. The success of root canal
      treatment largely depends on the elimination of microbial contamination from the
      root canal system. Although mechanical instrumentation of root canals can reduce
      bacterial population, effective elimination of bacteria cannot be achieved
      without the use of antimicrobial root canal irrigation and medication. This
      review will discuss the antimicrobial effects of the known root canal irrigants
      and medicaments and explore future developments in the field.

PMID- 17223591
TI  - Invasive cervical resorption: clinical and radiological diagnosis and treatment
      of 3 cases.
AB  - Invasive cervical resorption is a relatively uncommon form of external root
      resorption. Etiologic factors include trauma, orthodontic treatment, intracoronal
      bleaching, and inflammation, but invasive cervical resorption is often
      idiopathic. There may be no external signs of this disorder, and the resorptive
      lesion is often detected by routine radiographic examination. This article
      describes the clinical and radiological diagnoses and treatment modalities of
      invasive cervical resorption in 3 patients. Two of the 3 cases were incidental
      radiographic findings and the teeth concerned were symptom free. One case was
      symptomatic due to periodontal infection. Computed tomography (CT) evaluation was
      performed in the 2 symptom-free patients. Thus, exact size and localization of
      the resorptive lesions were obtained. In 2 cases, root canal treatment was
      performed, and in the other case the resorptive defect was sealed with mineral
      trioxide aggregate.

PMID- 17223592
TI  - Osteonecrosis of the jaws associated with use of risedronate: report of 2 new
      cases.
AB  - Use of various bisphosphonates has been associated with the development of
      osteonecrosis of the jaws (ONJ). At least 865 cases of ONJ attributed to these
      agents have been reported in the English-language literature. Approximately 96%
      of these published cases were seen with administration of the intravenous agents
      pamidronate and zoledronate, whereas only 26 cases have been associated with oral
      bisphosphonates, 25 of them with alendronate. Only a single case of ONJ
      associated with the oral bisphosphonate risedronate has been previously cited. We
      report 2 cases of ONJ attributed to risedronate administration. The patients
      developed osteonecrosis 15 and 24 months after treatment for osteopenia. A
      regimen of antibiotics and chlorhexidine mouthrinse resolved the osseous defect
      in the mandible caused by complete exfoliation of a lingual torus in 1 patient.
      The other patient required sequestrectomy, repeated courses of antibiotics,
      surgical debridement, and steroids to promote closure of an oroantral fistula and
      management of sinusitis after bone grafting and implant placement in the
      posterior maxilla. A demographic profile of reported oral bisphosphonate users
      affected by ONJ is also provided. With the millions of patients receiving various
      oral bisphosphonates for osteopenia and osteoporosis, health care practitioners
      should be aware of the potential for the onset of osteonecrosis and familiar with
      its management.

PMID- 17223593
TI  - G6PD (AC)n and (CTT)n microsatellites in Mexican Mestizos with common G6PD
      African variants.
AB  - Genotyping for the G6PD (AC)n and (CTT)n microsatellites in a sample of 58
      Mexican Mestizos with common G6PD African variants was carried out. The second
      mutation that defines to the variants G6PD A(-202A/376G), G6PD
      Santamaria(376G/542T) and G6PD A(-376G/968C) very probably occurred on G6PD
      A(376G) chromosomes with the compound haplotypes, intragenic silent polymorphisms
      and microsatellites, Pvu-II/Pst-I/Bcl-I/Nla-III/(AC)n/(CTT)n: +/+/-/+/166 bp/195
      bp, -/+/-/+/166 bp/201 bp, and -/+/-/+/166 bp/204 bp respectively. The structure
      of the repeat sequences for the AC-166 bp allele in the 3 variants was
      (TA)5(AA)1(TA)9(CA)10 whereas the repeat sequences for the CTT-195 bp, CTT-201 bp
      and CTT-204 bp alleles were (CTT)11(ATT)6, (CTT)7(ATT)12 and (CTT)7(ATT)13 in the
      first, second and third variants respectively. Genotyping for the G6PD
      microsatellites can be a useful tool with several applications.

PMID- 17223594
TI  - Ciona intestinalis as a model for cardiac development.
AB  - The primitive chordate Ciona intestinalis has emerged as a significant model
      system for the study of heart development. The Ciona embryo employs a conserved
      heart gene network in the context of extremely low cell numbers and reduced
      genetic redundancy. Here, I review recent studies on the molecular genetics of
      Ciona cardiogenesis as well as classic work on heart anatomy and physiology. I
      also discuss the potential of employing Ciona to decipher a comprehensive
      chordate gene network and to determine how this network controls heart
      morphogenesis.

PMID- 17223595
TI  - Nitric oxide red blood cell membrane permeability at high and low oxygen tension.
AB  - Red blood cell (RBC) encapsulated hemoglobin in the blood scavenges nitric oxide
      (NO) much more slowly than cell-free hemoglobin would. Part of this reduced NO
      scavenging has been attributed to an intrinsic membrane barrier to diffusion of
      NO through the RBC membrane. Published values for the permeability of RBCs to NO
      vary over several orders of magnitude. Recently, the rate that RBCs scavenge NO
      has been shown to depend on the hematocrit (percentage volume of RBCs) and oxygen
      tension. The difference in rate constants was hypothesized to be due to oxygen
      modulation of the RBC membrane permeability, but also could have been due to the
      difference in bimolecular rate constants for the reaction of NO and oxygenated vs
      deoxygenated hemoglobin. Here, we model NO scavenging by RBCs under previously
      published experimental conditions. A finite-element based computer program model
      is constrained by published values for the reaction rates of NO with oxygenated
      and deoxygenated hemoglobin as well as RBC NO scavenging rates. We find that the
      permeability of RBCs to NO under oxygenated conditions is between 4400 and 5100
      microm s(-1) while the permeability under deoxygenated conditions is greater than
      64,000 microm s(-1). The permeability changes by a factor of 10 or more upon
      oxygenation of anoxic RBCs. These results may have important implications with
      respect to NO import or export in physiology.

PMID- 17223597
TI  - On representation of proteins by star-like graphs.
AB  - To arrive at graphical representations of proteins one is confronted with number
      of arbitrary decisions how to assign the 20 natural amino acids to equivalent or
      non-equivalent sites of underlying geometrical objects used for construction of
      their graphical representation. Here we consider representation of proteins based
      on generalized star graphs, which are graphs with one vertex of maximal degree in
      the center to which are attached other vertices of either degree one or two. The
      matrix representation of proteins based on star-like graphs has an important
      advantage in that, while its pictorial representation depends on selected
      assignment of amino acids to various branches of star graph, its properties do
      not depend on the adopted assignment of vertices to amino acids. Hence, the
      derived graph invariants, devoid of artifacts associated with graphical
      representations of biosequences, will better reflect upon the inherent properties
      of protein structure. We describe several graph invariants, mostly extracted from
      distance matrices of star-like graphs, which can serve as protein descriptors.
      The approach is illustrated on strand A of the human insulin.

PMID- 17223598
TI  - Growth hormone (GH) replacement therapy in GH deficient adults: predictors of one
      year metabolic and clinical response.
AB  - OBJECTIVE: This study investigated whether baseline status could predict the
      responsiveness to one-year growth hormone (GH) replacement therapy in adult GH
      deficient (GHD) patients. DESIGN: A total of 380 European patients with adult
      onset GHD due to non-functioning pituitary adenoma that had been enrolled in
      Pfizer International Metabolic Database (KIMS), and that had completed one year
      of GH replacement therapy within KIMS, were studied. RESULTS: The mean initial
      dose of GH was 0.22 (SEM 0.01) mg/day and after one year, the mean dose was 0.36
      (0.01) mg/day. The mean insulin-like growth factor-I (IGF-I) SD score increased
      from -1.75 (0.08) at baseline to 0.47 (0.05) after one year. Quality of life
      (QoL)-Assessment of GHD in Adults (QoL-AGHDA), waist circumference, waist:hip
      ratio, and serum lipid pattern improved. Women received a higher dose of GH than
      men after one year, and demonstrated similar treatment response. In multiple
      stepwise forward regression analyses, the one-year changes in QoL-AGHDA score,
      waist:hip ratio, and serum low density lipoprotein-cholesterol (LDL-C) level
      correlated inversely with the baseline values of the same variable. In addition,
      the change after one year in QoL-AGHDA score correlated inversely with duration
      of hypopituitarism and baseline serum high density lipoprotein-cholesterol (HDL
      C) level, and the change in waist:hip ratio correlated inversely, although more
      weakly, with baseline serum HDL-C level and UK citizenship and positively with
      baseline waist circumference and the initial GH dose. The change in serum LDL-C
      level additionally correlated inversely with the mean GH dose and duration of
      hypopituitarism and positively with UK citizenship. CONCLUSIONS: Baseline status
      could, with moderate strength, predict the responsiveness in the same variable
      whereas it could not, or only weakly, predict the response in other variables.
      Therefore, when the decision to start GH replacement is undertaken, as many
      outcome variables as possible should be evaluated in order to adequately evaluate
      the likelihood of clinical benefit. Finally, women have a similar response to GH
      replacement as men when individualised GH dosing schedules are employed and
      should therefore be selected for GH therapy to a similar extent.

PMID- 17223596
TI  - Simultaneous detection of resolved glutamate, glutamine, and gamma-aminobutyric
      acid at 4 T.
AB  - A new approach is introduced to simultaneously detect resolved glutamate (Glu),
      glutamine (Gln), and gamma-aminobutyric acid (GABA) using a standard STEAM
      localization pulse sequence with the optimized sequence timing parameters. This
      approach exploits the dependence of the STEAM spectra of the strongly coupled
      spin systems of Glu, Gln, and GABA on the echo time TE and the mixing time TM at
      4 T to find an optimized sequence parameter set, i.e., {TE, TM}, where the outer
      wings of the Glu C4 multiplet resonances around 2.35 ppm, the Gln C4 multiplet
      resonances around 2.45 ppm, and the GABA C2 multiplet resonance around 2.28 ppm
      are significantly suppressed and the three resonances become virtual singlets
      simultaneously and thus resolved. Spectral simulation and optimization were
      conducted to find the optimized sequence parameters, and phantom and in vivo
      experiments (on normal human brains, one patient with traumatic brain injury, and
      one patient with brain tumor) were carried out for verification. The results have
      demonstrated that the Gln, Glu, and GABA signals at 2.2-2.5 ppm can be well
      resolved using a standard STEAM sequence with the optimized sequence timing
      parameters around {82 ms,48 ms} at 4 T, while the other main metabolites, such as
      N-acetyl aspartate (NAA), choline (tCho), and creatine (tCr), are still preserved
      in the same spectrum. The technique can be easily implemented and should prove to
      be a useful tool for the basic and clinical studies associated with metabolism of
      Glu, Gln, and/or GABA.

PMID- 17223599
TI  - Amino acid change 335 E to K affects the sialic-acid-binding and neuraminidase
      activities of Urabe AM9 mumps virus hemagglutinin-neuraminidase glycoprotein.
AB  - A mutation coding for the amino acid change E335 to K is frequently found in the
      hemagglutinin-neuraminidase (HN) gene of Urabe AM9 mumps viruses isolated during
      post-vaccination meningitis cases. To identify if this mutation modifies the
      biological activities of the HN glycoprotein, two variants of Urabe AM9 vaccine
      differing at amino acid 335 (HN-E335 and HN-K335) were isolated and their
      receptor-binding specificity was determined by means of competence assays. Pre
      incubation of the viruses with sialic acids inhibited both syncytia formation in
      Vero cells and replication in SH-SY5Y cells. Thus, HN-K335 showed higher affinity
      towards sialylalpha2,6lactose, whereas HN-G335 preferred sialylalpha2,3lactose.
      These results are relevant because a high expression of sialylalpha2,6lactose in
      nerve cells was confirmed by means of Sambucus nigra lectin-cytochemistry. In
      addition, kinetics assays showed that HN-K335 and HN-E335 also differ in their
      hydrolysis rate (Vmax values of 37.5 vs. 3.5 nmol min-1mg-1, respectively).
      Therefore, HN-K335 variant presented a neuraminidase activity level 11-fold
      higher than that of HN-E335 variant. In conclusion, the mutation affects the
      receptor-binding and neuraminidase activities of Urabe AM9 mumps virus variants.

PMID- 17223600
TI  - Age-dependent impairment of functional helper T cell responses to immunodominant
      epitopes of Toxoplasma gondii antigens in congenitally infected individuals.
AB  - Human infection with Toxoplasma gondii is generally asymptomatic in
      immunocompetent adults while it causes significant morbidity in congenitally
      infected children. Cell mediated immunity plays the main role in host resistance
      to T. gondii infection and a Th1 cytokine profile is necessary for protection and
      control of infection. The present work focused on comparing the helper T cell
      response to the GRA1 antigen of the parasite between children with congenital
      toxoplasmosis and healthy adults with acquired infection. We demonstrated that in
      young children with congenital infection the specific T cell response to parasite
      antigens is impaired and that such hypo-responsiveness is restored during
      childhood. Also, we provided clear evidence that in individuals with congenital
      toxoplasmosis the acquisition of functional helper T cell responses is disease
      unrelated and indistinguishable in terms of strength, epitope specificity, and
      cytokine profile from the corresponding responses in immunocompetent adults with
      asymptomatic acquired T. gondii infection.

PMID- 17223601
TI  - Plasma levels of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1)
      in familial Mediterranean fever.
AB  - AIMS: To assess the levels of soluble vascular endothelial growth factor receptor
      1 (sVEGFR-1) in patients with familial Mediterranean fever (FMF). METHODS: Plasma
      levels of sVEGFR-1 were investigated in 33 FMF patients in an attack-free period
      (mean age 30.8 years; males/females 10/23), in 15 patients with acute FMF attack
      (mean age 32.7 years; males/females 7/8), and 19 healthy controls (mean age 32
      years; males/females 11/8). Levels of sVEGFR-1 were also compared among patients
      who were receiving colchicine and those who were not. RESULTS: Plasma sVEGFR-1
      levels were 3.49+/-1.10, 3.53+/-1.02, and 0.37+/-0.28 ng/ml for FMF patients in
      the attack-free period, FMF patients with acute attack, and healthy controls,
      respectively. Plasma sVEGFR-1 levels were significantly higher in FMF patients
      with and without acute attack compared to the control group (p<0.05). sVEGFR-1
      levels were not statistically significant between patients with acute attack and
      attack-free FMF patients (p>0.05). The plasma levels of sVEGFR-1 were also
      comparable in colchicine treated and untreated patients. CONCLUSION: Our data
      suggest that sVEGFR-1 may have a role in the ongoing inflammatory cascade in FMF.

PMID- 17223602
TI  - The efficacy of balneotherapy and mud-pack therapy in patients with knee
      osteoarthritis.
AB  - OBJECTIVES: Knee osteoarthritis (OA) is a common chronic degenerative disorder.
      There are various treatment modalities. This study was planned to investigate the
      efficacy of balneotherapy, mud-pack therapy in patients with knee OA. METHODS: A
      total of 80 patients with knee OA were included. Their ages ranged between 39-78.
      The patients were separated in to three groups. Group I (n=25) received
      balneotherapy, group II (n=29) received mud-pack therapy and group III (n=26) was
      hot-pack therapy group. The therapies were applied for 20 min duration, once a
      day, five times per week and a total of 10 session. Patients were assessed
      according to pain, functional capacity and quality of life parameters. Pain was
      assessed by using Visual Analogue Scale (VAS) and Western Ontario McMaster
      Osteoarthritis Index (WOMAC) pain scale (0-4 likert scale). Functional capacity
      was assessed by using WOMAC functional capacity and WOMAC global index. Quality
      of life was evaluated by Nottingham Health Profile (NHP) self-administered
      questionnaire. Also physician's global assessment and the maximum distance that
      patient can walk without pain, were evaluated. The assessment parameters were
      evaluated before and after three months. RESULTS: There were statistically
      significant improvement in VAS and WOMAC pain scores in group I (p<0.001), group
      II and III (p<0.05). The WOMAC functional and global index also decreased in
      group I (p<0.05), group II (p<0.001) and hot-pack group (p<0.05). Quality of life
      results were significantly improved in balneotherapy and mud-pack therapy groups
      (p<0.05). No difference was observed in hot-pack therapy group (p>0.05). The
      maximum distance was improved both in group I and II (p<0.05) but not in group
      III. Also physician's global assessment was found to be improved in all groups
      (p<0.05). CONCLUSIONS: Balneotherapy and mud-pack therapy were effective in
      treating patients with knee OA.

PMID- 17223603
TI  - [Embryo donation in France: practice and difficulties. Strasbourg's experience].
AB  - OBJECTIVE: The aim of this study was to present the situation of embryo donation
      in France and around the world, to expound the difficulties of its practice and
      the results obtained in our centre 3 years after the introduction of this
      procedure. PATIENTS AND METHODS: Embryo donation in France is controlled by
      implemented decrees published between 1999 and 2004. The couples, who have stored
      frozen embryos since at least two years, were contacted for a pluridisciplinary
      medical consultation. The indication of embryo donation was evaluated for the
      recipients through a pluridisciplinary approach. RESULTS: Among the interviewed
      couples, 16.7% have chosen embryo donation but only half of them have completed
      the procedure (6% of the couples with frozen embryos). The main indications for
      embryo donation were a double sterility, unexplained genetic disease, ART
      failures (poor fertilization or bad embryo quality) and oocyte donation when the
      delay was too long for the couples. The pregnancy rate was 28.6% after the 21
      first embryo transfers. DISCUSSION AND CONCLUSION: The results of embryo donation
      confirm the international experience both considering the poor number of donated
      embryos, medical indications and results. Embryo donation has its place among ART
      techniques, but one should not ignore the general debate on ethical questions
      raised by this procedure.

PMID- 17223604
TI  - [Surgical treatment of stress urinary incontinence by suburethral transobturator
      tape].
AB  - OBJECTIVE: Assessment of the suburethral transobturator tape in the treatment of
      female urinary stress incontinence. PATIENTS AND METHODS: Retrospective
      evaluation of 39 slings. Three patients (7%) were lost to follow-up. Analysis was
      carried on 19 out/in procedures (mainly ObTape and Uratape slings) and 17 in/out
      procedures (TVT-O slings). Nine patients (25%) had a history of previous stress
      incontinence surgery. In 21 cases (58%) there was a concomitant surgical
      procedure, including genital prolapse repair (12) and total hysterectomy (6).
      Phone interviews were conducted with the validated questionnaires MHU and
      Ditrovie short form. RESULTS: The mean operative time was 17 minutes (10-30).
      Three vaginal wounds (8%) were immediately repaired. Two urinary retentions (5%)
      were managed by suprapubic catheterization for more than 10 days. With a mean
      follow-up of 12 months (4-23) the subjective effectiveness on stress incontinence
      was 89% (cure: 58%; improvement: 31%). Urge incontinence symptoms were cured in
      47% of mixed incontinences. Two patients reported an important dysuria. Two sling
      exposures occurred. Quality of life scores were significantly improved (mean 1,7
      versus 3,2, p=0,002). The level of satisfaction reached 89% (very satisfied: 50%;
      satisfied: 39%). DISCUSSION AND CONCLUSION: This technique is safe and effective.
      Our results are nevertheless inferior to those previously reported. Prospective
      randomised studies comparing the two surgical routes are required.

PMID- 17223605
TI  - [Interstitial Pregnancy. Ultrasonographic diagnosis and contribution of MRI. A
      case report].
AB  - We report ultrasonographic features of interstitial pregnancy and propose three
      magnetic resonance imaging criteria for the interstitial pregnancy localization.
      These criteria may facilitate the differentiation between an interstitial
      pregnancy and an angular pregnancy. The magnetic resonance imaging may be used
      whenever ultrasound examination diagnosis of an interstitial pregnancy is
      equivocal.

PMID- 17223606
TI  - [Anti-papillomavirus vaccine: the dream has come true].

PMID- 17223607
TI  - Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human
      lymphoblastoid cells.
AB  - Titanium dioxide is frequently used in the production of paints, paper, plastics,
      welding rod-coating material, and cosmetics, because of its low toxicity.
      However, recent studies have shown that nano-sized or ultrafine TiO(2) (UF
      TiO(2)) (<100 nm in diameter) can generate pulmonary fibrosis and lung tumor in
      rats. Cytotoxicity induced by UF-TiO(2) in rat lung alveolar macrophages was also
      observed. This generates great concern about the possible adverse effects of UF
      TiO(2) for humans. The cytotoxicity and genotoxicity of UF-TiO(2) were
      investigated using the methyl tetrazolium cytotoxicity (MTT) assay, the
      population growth assay, the apoptosis assay by flow cytometry, the cytokinesis
      block micronucleus (CBMN) assay, the comet assay, and the hypoxanthine-guanine
      phosphoribosyltransferase (HPRT) gene mutation assay. WIL2-NS cells were
      incubated for 6, 24 and 48 h with 0, 26, 65 and 130 microg/ml UF-TiO(2).
      Significant decreases in viability were seen in the MTT assay at higher doses;
      for example, 61, 7 and 2% relative viability at 130 microg/ml for 6, 24 and 48-h
      exposure (P<0.01). A dose-dependent relationship was observed, while a time
      dependent relationship was seen only at the highest dose (130 microg/ml) after
      exposure for 24 and 48 h. Treatment with 130 microg/ml UF-TiO(2) induced
      approximately 2.5-fold increases in the frequency of micronucleated binucleated
      cells (P<0.01). In addition, a significant reduction in the cytokinesis block
      proliferation index was observed by the CBMN assay (P<0.05). In the comet assay,
      treatment with 65 microg/ml UF-TiO(2) induced approximately 5-fold increases in
      olive tail moment (P<0.05). In the HPRT mutation assay, treatment with 130
      microg/ml UF-TiO(2) induced approximately 2.5-fold increases in the mutation
      frequency (P<0.05). The results of this study indicate that UF-TiO(2) can cause
      genotoxicity and cytotoxicity in cultured human cells.

PMID- 17223609
TI  - Multiplex PCR approach for species detection and differentiation within the genus
      Spirostomum (Ciliophora, Heterotrichea).

PMID- 17223608
TI  - Prozone effect with the VIDAS HIV DUO Ultra assay.

PMID- 17223611
TI  - Echocardiographic diagnosis of left ventricular-right atrial communication
      (Gerbode-type defect) in an adult with chronic renal failure: a case report.
AB  - Left ventricular-right atrial communication, known as a Gerbode-type defect, is a
      rare form of ventricular septal defect. It is usually congenital, but rarely
      acquired. Clinical presentation is associated with the volume of the shunt.
      Transthoracic echocardiography is the most useful diagnostic method. We present a
      63-year-old man with chronic renal failure and left ventricular-right atrial
      shunt.

PMID- 17223612
TI  - Early inflammation in the airways of a cystic fibrosis foetus.
AB  - In cystic fibrosis patients, inflammation is often considered to be secondary to
      chronic infections. In the present study, we show increased levels of pro
      inflammatory proteins in the lungs of a cystic fibrosis foetus compared to the
      lungs of two normal foetuses. Our findings suggest therefore the existence of an
      early intrinsic pro-inflammatory state in cystic fibrosis airways.

PMID- 17223615
TI  - Do egg-laying crocodilian (Alligator mississippiensis) archosaurs form medullary
      bone?
AB  - It is beyond question that Mesozoic dinosaurs, like Aves and Crocodylia, are
      archosaurs. However, within the archosaurian clade, the origin and distribution
      of some major features are less clear, particularly with respect to reproductive
      physiology. Medullary bone, a highly mineralized, bony reproductive tissue
      present in the endosteal cavities of all extant egg-laying birds thus far
      examined, has recently been reported in Tyrannosaurus rex. Its presence or
      absence in extant crocodilians, therefore, may shed light on the timing of its
      evolutionary appearance. If medullary bone is present in all three taxa, it arose
      before the three lineages diverged. However, if medullary bone arose after this
      divergence, it may be present in both extinct dinosaurs and birds, or in birds
      only. If present in extinct dinosaurs and birds, but not crocodilians, it would
      indicate that it arose in the common ancestor of this clade, thus adding support
      to the closer phylogenetic relationship of dinosaurs and birds relative to
      crocodilians. Thus, the question of whether the crocodilian Alligator
      mississippiensis forms medullary bone during the production of eggs has important
      evolutionary significance. Our examination of long bones from several alligators
      (two alligators with eggs in the oviducts, one that had produced eggs in the past
      but was not currently in reproductive phase, an immature female and an adult
      male) shows no differences on the endosteal surfaces of the long bones, and no
      evidence of medullary bone, supporting the hypothesis that medullary bone first
      evolved in the dinosaur-bird line, after the divergence of crocodilians from this
      lineage.

PMID- 17223614
TI  - The A1330V polymorphism of the low-density lipoprotein receptor-related protein 5
      gene (LRP5) associates with low peak bone mass in young healthy men.
AB  - INTRODUCTION: Polymorphisms in the gene coding for low-density lipoprotein
      receptor-related protein 5 (LRP5) contribute to variation in bone mass in the
      general population. Whether this is due to influence on bone mass acquisition or
      on bone loss thereafter has not been established. METHODS: We studied the
      association of LRP5 polymorphisms with peak bone mass in young men. The study
      included 235 Finnish men, aged 18.3 to 20.6 years. Lifestyle factors and fracture
      history were recorded. Bone mineral content (BMC), density (BMD) and scan area
      were measured for the lumbar spine and proximal femur by dual energy X-ray
      absorptiometry (DXA). Blood and urine were collected for determination of bone
      turnover markers, serum 25-OHD and PTH. Genomic DNA was extracted from peripheral
      blood for genetic analysis of LRP5. Ten single nucleotide polymorphisms in LRP5
      were analyzed and correlated with bone parameters. RESULTS: Only the A1330V
      polymorphism of LRP5 significantly associated with bone parameters. In comparison
      with subjects with the AlaAla genotype (n=215), those with AlaVal genotype (n=20)
      had lower femoral neck BMC (P=0.029) and BMD (P=0.012), trochanter BMC (P=0.0067)
      and BMD (P=0.015), and total hip BMC (P=0.0044) and BMD (P=0.0089). Fracture
      history was similar for the genotypes. CONCLUSION: The polymorphic valine variant
      at position 1330 of LRP5 was significantly associated with reduced BMC and BMD
      values in healthy young Finnish men. The results provide evidence for the crucial
      role of LRP5 in peak bone mass acquisition.

PMID- 17223616
TI  - Discriminative ability of dual-energy X-ray absorptiometry site selection in
      identifying patients with osteoporotic fractures.
AB  - Dual-energy X-ray absorptiometry (DXA) is the gold standard method for
      measurement of bone mineral density (BMD). The aims of the current study are to
      compare the ability of BMD measurements to identify subjects with vertebral
      fractures (VF), when the lumbar spine (LS), hip or both sites are measured. 460
      subjects aged 73+/-5.2 years participated in the study. Thoraco-lumbar spine
      radiographs were obtained and analyzed for the presence of VF using the visual
      semi-quantitative assessment. BMD of the LS and the left femur were measured by
      DXA. Eighteen men (12%) and 56 women (20%) had at least one VF. 16% of scans at
      the LS were unreadable because of the presence of degenerative changes. In both
      genders, BMD of the hip showed better ability than LS BMD in detecting subjects
      with osteoporosis. BMD and T-score values at the hip, but not the LS, were lower
      in subjects with VF than those without (p<0.05). Femoral neck BMD showed the
      highest OR for each S.D. decrease in BMD for identifying subjects with VF, and
      the best predictability for prevalent VF using ROC. Fracture risk prediction did
      not increase by adding the spine to the hip measurement. In conclusion, hip BMD
      was the only and best skeletal site needed to detect subjects with osteoporosis
      and showed the strongest relationship with prevalent vertebral fractures in
      elderly subjects.

PMID- 17223613
TI  - The role of NADPH oxidase in carotid body arterial chemoreceptors.
AB  - O(2)-sensing in the carotid body occurs in neuroectoderm-derived type I glomus
      cells where hypoxia elicits a complex chemotransduction cascade involving
      membrane depolarization, Ca(2+) entry and the release of excitatory
      neurotransmitters. Efforts to understand the exquisite O(2)-sensitivity of these
      cells currently focus on the coupling between local P(O2) and the open-closed
      state of K(+)-channels. Amongst multiple competing hypotheses is the notion that
      K(+)-channel activity is mediated by a phagocytic-like multisubunit enzyme, NADPH
      oxidase, which produces reactive oxygen species (ROS) in proportion to the
      prevailing P(O2). In O(2)-sensitive cells of lung neuroepithelial bodies (NEB),
      multiple studies confirm that ROS levels decrease in hypoxia, and that E(M) and
      K(+)-channel activity are indeed controlled by ROS produced by NADPH oxidase.
      However, recent studies in our laboratories suggest that ROS generated by a non
      phagocyte isoform of the oxidase are important contributors to chemotransduction,
      but that their role in type I cells differs fundamentally from the mechanism
      utilized by NEB chemoreceptors. Data indicate that in response to hypoxia, NADPH
      oxidase activity is increased in type I cells, and further, that increased ROS
      levels generated in response to low-O(2) facilitate cell repolarization via
      specific subsets of K(+)-channels.

PMID- 17223617
TI  - Long-bone changes after pamidronate discontinuation in children and adolescents
      with osteogenesis imperfecta.
AB  - Cyclical intravenous pamidronate is a widely used symptomatic therapy in moderate
      to severe osteogenesis imperfecta (OI). The effects of treatment discontinuation
      on long bone development have not been characterized. In this observational study
      we used peripheral quantitative computed tomography to assess the radius at the
      distal metaphysis and at the diaphysis in 23 young OI patients (11 female) who
      had received pamidronate for at least 3 years. Measurements were performed twice,
      at the time of treatment discontinuation (when the age of the patients ranged
      from 5.9 to 21.3 years) and at an average of 1.9 years (range 1.5 to 2.4 years)
      later. At the time of pamidronate discontinuation, all but one of the patients
      who were below 15 years of age (n=14) had a positive age- and sex-specific z
      score for bone mineral content (BMC) at the metaphysis, resulting in a mean z
      score of +2.0 (SD=1.0) for this subgroup. In contrast, patients aged 15 years or
      older (n=9) had an average metaphyseal BMC z-score of -1.5 (SD=1.5). After
      pamidronate discontinuation, metaphyseal BMC z-score decreased by an average of
      2.4 (SD=2.0) in the whole group. The change in BMC z-score was growth-dependent,
      as BMC z-scores decreased by about 2 or more in all patients in whom distal
      radius growth plates were open when pamidronate was discontinued. In contrast,
      none of the 11 patients with closed distal radius growth plates experienced a
      decrease in metaphyseal BMC z-score by more than 2. At the diaphysis, the average
      BMC z-score was low at the time of the last pamidronate infusion [z-score -1.7
      (SD=1.4)]. After pamidronate discontinuation, the average diaphyseal BMC z-score
      decreased by only 0.3 (SD=0.4). In summary, this study shows that the effect of
      pamidronate discontinuation is much larger at the radial metaphysis than at the
      diaphysis and is dependent on growth. Metaphyseal bone tissue added by
      longitudinal growth after treatment discontinuation has a lower density than
      tissue created during treatment. It is possible that this produces zones of
      localized bone fragility after pamidronate treatment is stopped in growing
      children.

PMID- 17223618
TI  - Age-dependent change in the 3D structure of cortical porosity at the human
      femoral midshaft.
AB  - Microstructural change associated with cortical bone remodeling has been
      extensively explored with 2D techniques. However, relatively little is known
      regarding the 3D dynamic microstructure of cortical bone. Therefore, we employed
      micro-CT imaging to investigate 3D remodeling-related change in the structure of
      cortical bone porosity across the human lifespan. Anterior femoral midshaft
      specimens (n=51 male, 28 female) spanning 18 to 92 years of age were scanned with
      7 mum nominal isotropic resolution. Canal volume fraction (Ca.V/TV), mean
      diameter (Ca.Dm), mean separation (Ca.Sp), degree of anisotropy (DA),
      connectivity density (Ca.ConnD), and number (Ca.N) were calculated for
      subperiosteal cylindrical regions of interest. Ca.N was calculated in 2D
      (Ca.N(2D)) and 3D (Ca.N(3D)). Regression was used to examine the relation between
      the structural parameters and age. Additionally, the impact of sex, height, and
      weight were investigated collectively (MANCOVA) and individually (ANCOVA). For
      all analyses, Ca.V/TV and Ca.Dm were inverted (Ca.V/TV(-1), Ca.Dm(-1)) to
      establish normality and linear relations with age. Ca.N values (2D and 3D) were
      non-linearly (quadratic) related to age, increasing until the 6th decade then
      decreasing. This relation was only significant for the pooled sexes Ca.N(3D)
      values (p=0.012). Ca.ConnD was positively related to age (p<0.05), while all
      remaining 3D parameters, except DA for males (p=0.070), were negatively related
      (p<0.05). In all cases, the relation with age was strongest for females. MANCOVA
      revealed that age was the only significant (p<0.001) covariate overall.
      Univariate ANCOVA indicated significant differences between the sexes for
      Ca.V/TV(-1) and Ca.Dm(-1) (p=0.018 and 0.010, respectively). Relative to males,
      females had lower values for these parameters, translating into larger mean canal
      diameter and overall porosity. Body weight had a significant (p=0.043) positive
      relation with Ca.Dm(-1), indicating lower weight was also associated with
      increased mean canal diameter. Therefore, while age was the most important
      factor, sex and body size were found to play a role in parameters related to
      canal size and the overall level of porosity. This study is unique in that
      changes in cortical bone microstructure were examined across the adult human
      lifespan in three rather than two dimensions.

PMID- 17223620
TI  - Rat bite fever and Streptobacillus moniliformis.
AB  - Rat bite fever, caused by Streptobacillus moniliformis, is a systemic illness
      classically characterized by fever, rigors, and polyarthralgias. If left
      untreated, it carries a mortality rate of 10%. Unfortunately, its nonspecific
      initial presentation combined with difficulties in culturing its causative
      organism produces a significant risk of delay or failure in diagnosis. The
      increasing popularity of rats and other rodents as pets, together with the risk
      of invasive or fatal disease, demands increased attention to rat bite fever as a
      potential diagnosis. The clinical and biological features of rat bite fever and
      Streptobacillus moniliformis are reviewed, providing some distinguishing features
      to assist the clinician and microbiologist in diagnosis.

PMID- 17223621
TI  - Viral determinants of resistance to treatment in patients with hepatitis C.
AB  - Chronic hepatitis C virus (HCV) infection affects more than 170 million persons
      worldwide and is responsible for the development of liver cirrhosis in many
      cases. Standard treatment with pegylated alpha interferon (IFN-alpha) in
      combination with the nucleoside analogue ribavirin leads to a sustained virologic
      response in approximately half of the patients. IFN-alpha is classified as an
      indirect treatment, as it interacts with the host's immune response. The
      mechanism of action of ribavirin is still unknown. The benefit of triple therapy
      by adding other antiviral agents, e.g., amantadine, is controversial. Currently,
      new direct antiviral drugs (HCV protease/polymerase inhibitors) are being
      evaluated in phase 1/phase 2 trials. Phenotypic resistance to antiviral therapy
      has been attributed to amino acid variations within distinct regions of the HCV
      polyprotein. While sensitivity to IFN-alpha-based antiviral therapy in vivo is
      clearly correlated with the number of mutations within the HCV NS5A protein, the
      underlying functional mechanisms for this association are unknown. In turn, in
      vitro, several mechanisms to circumvent the host immune defense or to block
      treatment-induced antiviral activities have been described for different HCV
      proteins. By the introduction of direct antiviral drugs, hepatitis C therapy now
      is entering a new era in which the development of resistance may become the most
      important parameter for treatment success or failure.

PMID- 17223622
TI  - Global dissemination of Vibrio parahaemolyticus serotype O3:K6 and its
      serovariants.
AB  - Vibrio parahaemolyticus is recognized as a cause of food-borne gastroenteritis,
      particularly in the Far East, where raw seafood consumption is high. An unusual
      increase in admissions of V. parahaemolyticus cases was observed at the
      Infectious Diseases Hospital in Calcutta, a city in the northeastern part of
      India, beginning February 1996. Analysis of the strains revealed that a unique
      serotype, O3:K6, not previously isolated during the surveillance in Calcutta
      accounted for 50 to 80% of the infections in the following months. After this
      report, O3:K6 isolates identical to those isolated in Calcutta were reported from
      food-borne outbreaks and from sporadic cases in Bangladesh, Chile, France, Japan,
      Korea, Laos, Mozambique, Peru, Russia, Spain, Taiwan, Thailand, and the United
      States. Other serotypes, such as O4:K68, O1:K25, and O1:KUT (untypeable), that
      had molecular characteristics identical to that of the O3:K6 serotype were
      subsequently documented. These serotypes appeared to have diverged from the O3:K6
      serotype by alteration of the O:K antigens and were defined as "serovariants" of
      the O3:K6 isolate. O3:K6 and its serovariants have now spread into Asia, America,
      Africa, and Europe. This review traces the genesis, virulence features, molecular
      characteristics, serotype variants, environmental occurrence, and global spread
      of this unique clone of V. parahaemolyticus.

PMID- 17223623
TI  - Role of cell culture for virus detection in the age of technology.
AB  - Viral disease diagnosis has traditionally relied on the isolation of viral
      pathogens in cell cultures. Although this approach is often slow and requires
      considerable technical expertise, it has been regarded for decades as the "gold
      standard" for the laboratory diagnosis of viral disease. With the development of
      nonculture methods for the rapid detection of viral antigens and/or nucleic
      acids, the usefulness of viral culture has been questioned. This review describes
      advances in cell culture-based viral diagnostic products and techniques,
      including the use of newer cell culture formats, cryopreserved cell cultures,
      centrifugation-enhanced inoculation, precytopathogenic effect detection,
      cocultivated cell cultures, and transgenic cell lines. All of these contribute to
      more efficient and less technically demanding viral detection in cell culture.
      Although most laboratories combine various culture and nonculture approaches to
      optimize viral disease diagnosis, virus isolation in cell culture remains a
      useful approach, especially when a viable isolate is needed, if viable and
      nonviable virus must be differentiated, when infection is not characteristic of
      any single virus (i.e., when testing for only one virus is not sufficient), and
      when available culture-based methods can provide a result in a more timely
      fashion than molecular methods.

PMID- 17223624
TI  - Modes and modulations of antibiotic resistance gene expression.
AB  - Since antibiotic resistance usually affords a gain of function, there is an
      associated biological cost resulting in a loss of fitness of the bacterial host.
      Considering that antibiotic resistance is most often only transiently
      advantageous to bacteria, an efficient and elegant way for them to escape the
      lethal action of drugs is the alteration of resistance gene expression. It
      appears that expression of bacterial resistance to antibiotics is frequently
      regulated, which indicates that modulation of gene expression probably reflects a
      good compromise between energy saving and adjustment to a rapidly evolving
      environment. Modulation of gene expression can occur at the transcriptional or
      translational level following mutations or the movement of mobile genetic
      elements and may involve induction by the antibiotic. In the latter case, the
      antibiotic can have a triple activity: as an antibacterial agent, as an inducer
      of resistance to itself, and as an inducer of the dissemination of resistance
      determinants. We will review certain mechanisms, all reversible, that bacteria
      have elaborated to achieve antibiotic resistance by the fine-tuning of the
      expression of genetic information.

PMID- 17223625
TI  - Histoplasmosis: a clinical and laboratory update.
AB  - Infection with Histoplasma capsulatum occurs commonly in areas in the Midwestern
      United States and Central America, but symptomatic disease requiring medical care
      is manifest in very few patients. The extent of disease depends on the number of
      conidia inhaled and the function of the host's cellular immune system. Pulmonary
      infection is the primary manifestation of histoplasmosis, varying from mild
      pneumonitis to severe acute respiratory distress syndrome. In those with
      emphysema, a chronic progressive form of histoplasmosis can ensue. Dissemination
      of H. capsulatum within macrophages is common and becomes symptomatic primarily
      in patients with defects in cellular immunity. The spectrum of disseminated
      infection includes acute, severe, life-threatening sepsis and chronic, slowly
      progressive infection. Diagnostic accuracy has improved greatly with the use of
      an assay for Histoplasma antigen in the urine; serology remains useful for
      certain forms of histoplasmosis, and culture is the ultimate confirming
      diagnostic test. Classically, histoplasmosis has been treated with long courses
      of amphotericin B. Today, amphotericin B is rarely used except for severe
      infection and then only for a few weeks, followed by azole therapy. Itraconazole
      is the azole of choice following initial amphotericin B treatment and for primary
      treatment of mild to moderate histoplasmosis.

PMID- 17223631
TI  - The study of new calibration features in the Harshaw TLD system.
AB  - The Harshaw TLD system has three key calibration procedures: the Reader, the
      Dosemeter and the Algorithm. These functions must be properly calibrated for the
      system to achieve the optimum results. For the conventional reader and dosemeter
      calibration, Harshaw TLD recommends a pre-fade and a post-fade of 24-48 h when
      calibrating the system for LiF:Mg,Ti type dosemeter. It is also recommended that
      keeping the fade time consistent is important to maintain the quality of the
      system performance. In recent years, new calibration features have been
      introduced into the Harshaw TLD models 6600 and 8800 operating systems. These new
      features are Auto Calibration, Auto QC and Auto Blank, and they give the user the
      ability to set up the clear-expose-read process to be performed automatically in
      a sequence for each dosemeter. This saves processing time and keeps the fade time
      the same. However, since the fade time is near zero, will it affect the TLD
      system calibration factors? What should the user expect? This paper presents a
      study of the effect of Auto Calibration/Auto QC to the TLD operation.

PMID- 17223630
TI  - Understanding help seeking behaviour among male offenders: qualitative interview
      study.
AB  - OBJECTIVE: To explore the factors that influence help seeking for mental distress
      by offenders. DESIGN: Qualitative study based on in-depth interviews with
      prisoners before and after release. SETTING: One category B local prison in
      southern England. PARTICIPANTS: 35 male offenders aged 18-52, a quarter of whom
      had been flagged as being at risk of self harm. RESULTS: Most respondents
      reported that they would not seek help from a general practitioner or other
      healthcare professional if experiencing mental distress. When followed up after
      release, none had sought medical help despite the fact that many had considerable
      emotional problems. Many participants were hesitant to seek help because they
      feared being given a formal diagnosis of mental illness. Some of these men feared
      the stigma that such a diagnosis would bring, whereas others feared that a
      diagnosis would mean having to confront the problem. Lack of trust emerged as the
      most prominent theme in prisoners' discourse about not seeking help from health
      professionals. Distrust towards the "system" and authority figures in general was
      linked to adverse childhood experiences. Distrust directed specifically at
      healthcare professionals was often expressed as specific negative beliefs: many
      perceived that health professionals (most often doctors) "just don't care," "just
      want to medicate," and treat patients "superficially." Those men who would
      consider going to a general practitioner reported positive previous experiences
      of being respected and listened to. CONCLUSIONS: Distrust is a major barrier to
      accessing health care among offenders. Like most people, the respondents in this
      study wanted to feel listened to, acknowledged, and treated as individuals by
      health professionals. By ensuring that a positive precedent is set, particularly
      for sceptical groups such as ex-prisoners, general practitioners and prison
      doctors may be able to encourage future help seeking. Information specifically
      designed for prisoners is needed to help to de-stigmatise mental illness, and
      preparation for release should include provision of information about access to
      health and social services. Awareness training for health professionals is
      recommended: trust might be fostered in this population by seemingly trivial
      gestures that indicate respect.

PMID- 17223629
TI  - Oral chemotherapy safety practices at US cancer centres: questionnaire survey.
AB  - OBJECTIVE: To characterise current safety practices for the use of oral
      chemotherapy. DESIGN: Written questionnaire survey of pharmacy directors of
      cancer centres. SETTING: Comprehensive cancer centres in the United States.
      RESULTS: Respondents from 42 (78%) of 54 eligible centres completed the survey,
      after consulting with 89 colleagues. Clinicians at 29 centres used handwritten
      prescriptions, two used preprinted paper prescriptions, and six used electronic
      systems for most oral chemotherapy prescribing. For six commonly used oral
      chemotherapies, on average 10 centres required a diagnosis on the prescription,
      11 required the protocol number, four required the cycle number, nine required
      double checking by a second clinician, 14 required a calculation of body surface
      area, and 14 required a calculation of dose per square metre of body surface
      area. Only a third of centres requested patients' written informed consent when
      oral chemotherapy was given off protocol. Nearly a quarter (10) of centres had no
      formal process for monitoring patients' adherence. In the past year respondents
      at 10 centres reported at least one serious adverse drug event related to oral
      chemotherapy, and respondents at 13 centres reported a serious near miss.
      CONCLUSION: Few of the safeguards routinely used for infusion chemotherapy have
      been adopted for oral chemotherapy at US cancer centres. There is currently no
      consensus at these centres about safe medication practices for oral chemotherapy.

PMID- 17223628
TI  - Molecular epidemiology of malaria.
AB  - Malaria persists as an undiminished global problem, but the resources available
      to address it have increased. Many tools for understanding its biology and
      epidemiology are well developed, with a particular richness of comparative genome
      sequences. Targeted genetic manipulation is now effectively combined with in
      vitro culture assays on the most important human parasite, Plasmodium falciparum,
      and with in vivo analysis of rodent and monkey malaria parasites in their
      laboratory hosts. Studies of the epidemiology, prevention, and treatment of human
      malaria have already been influenced by the availability of molecular methods,
      and analyses of parasite polymorphisms have long had useful and highly
      informative applications. However, the molecular epidemiology of malaria is
      currently undergoing its most substantial revolution as a result of the genomic
      information and technologies that are available in well-resourced centers. It is
      a challenge for research agendas to face the real needs presented by a disease
      that largely exists in extremely resource-poor settings, but it is one that there
      appears to be an increased willingness to undertake. To this end, developments in
      the molecular epidemiology of malaria are reviewed here, emphasizing aspects that
      may be current and future priorities.

PMID- 17223632
TI  - Statistical modelling of Poisson/log normal data.
AB  - In statistical data fitting, self consistency is checked by examining the
      closeness of the quantity chi(2)/NDF to 1, where chi(2) is the sum of squares of
      data minus fit divided by standard deviation, and NDF is the number of data minus
      the number of fit parameters. In order to calculate chi(2) one needs an
      expression for the standard deviation. In this note several alternative
      expressions for the standard deviation of data distributed according to a
      Poisson/log-normal distribution are proposed and evaluated by Monte Carlo
      simulation. Two preferred alternatives are identified. The use of replicate data
      to obtain uncertainty is problematic for a small number of replicates. A method
      to correct this problem is proposed. The log-normal approximation is good for
      sufficiently positive data. A modification of the log-normal approximation is
      proposed, which allows it to be used to test the hypothesis that the true value
      is zero.

PMID- 17223627
TI  - Current therapeutics, their problems, and sulfur-containing-amino-acid metabolism
      as a novel target against infections by "amitochondriate" protozoan parasites.
AB  - The "amitochondriate" protozoan parasites of humans Entamoeba histolytica,
      Giardia intestinalis, and Trichomonas vaginalis share many biochemical features,
      e.g., energy and amino acid metabolism, a spectrum of drugs for their treatment,
      and the occurrence of drug resistance. These parasites possess metabolic pathways
      that are divergent from those of their mammalian hosts and are often considered
      to be good targets for drug development. Sulfur-containing-amino-acid metabolism
      represents one such divergent metabolic pathway, namely, the cysteine
      biosynthetic pathway and methionine gamma-lyase-mediated catabolism of sulfur
      containing amino acids, which are present in T. vaginalis and E. histolytica but
      absent in G. intestinalis. These pathways are potentially exploitable for
      development of drugs against amoebiasis and trichomoniasis. For instance, L
      trifluoromethionine, which is catalyzed by methionine gamma-lyase and produces a
      toxic product, is effective against T. vaginalis and E. histolytica parasites in
      vitro and in vivo and may represent a good lead compound. In this review, we
      summarize the biology of these microaerophilic parasites, their clinical
      manifestation and epidemiology of disease, chemotherapeutics, the modes of action
      of representative drugs, and problems related to these drugs, including drug
      resistance. We further discuss our approach to exploit unique sulfur-containing
      amino-acid metabolism, focusing on development of drugs against E. histolytica.

PMID- 17223633
TI  - A comparative study on the susceptibility of LiF:Mg,Ti (TLD-100) and LiF:Mg,Cu,P
      (TLD-100H) to spurious signals in thermoluminescence dosimetry.
AB  - It is well known that spurious signals can occur in thermoluminescence dosimetry
      (TLD) whenever contaminants (i.e. dirt, oil, dust) are present on the surface of
      the TLD card or crystal during the read-out process. For TLD cards, the Teflon
      material can also contribute to the background noise and this contribution has
      been found to depend on the material's light absorption. These non-radiation
      induced signals contribute to the total light output during TLD read-out and can
      lead to incorrect dosimetry especially for low-dose measurements such as personal
      dosimetry. However, these spurious signals are generally in the low-temperature
      channels and are mostly accompanied by abnormal glow curves. Most of the
      published reports dealing with this type of spurious TL signal are on the
      LiF:Mg,Ti (TLD-100) material. The relatively new TLD material, LiF:Mg,Cu,P, is
      more sensitive and has higher signal-to-noise ratio than the traditional
      LiF:Mg,Ti. In this study, the effects of disturbing signals to the LiF:Mg,Cu,P
      (TLD-100H) cards used in personal dosimetry are investigated and compared with
      those of LiF:Mg,Ti (TLD-100).

PMID- 17223634
TI  - Proton and photon absorbed-dose conversion coefficients for embryo and foetus
      from top-down irradiation geometry.
AB  - Absorbed-dose conversion coefficients are calculated for the embryo of 8 weeks
      and the foetus of 3, 6 or 9 months when the mother's body is exposed to protons
      and photons from top-down (TOP) direction. It provides data sets in addition to
      other standard irradiation geometries published previously. The TOP-irradiation
      geometry is considered here, because high-energy particles are often peaked from
      the TOP direction onboard aircrafts. The results show that absorbed-doses from
      high-energy particles could be underestimated significantly if isotropic (ISO)
      irradiation geometry is assumed. For protons of 100 GeV, absorbed-doses from TOP
      irradiation are approximately 2.3-2.9 times higher than the doses from ISO
      irradiation for different foetal ages. For 10 GeV photons, foetal doses from TOP
      irradiation are approximately 6.8-12 times higher than the doses from ISO
      irradiation. The coefficients from TOP-irradiation geometry are given in wide
      energy ranges, from 100 MeV to 100 GeV for protons and from 50 keV to 10 GeV for
      photons. They can, therefore, be used in various applications whenever exposure
      from the TOP-irradiation direction is concerned.

PMID- 17223635
TI  - Telomere length in mammalian cells exposed to low- and high-LET radiations.
AB  - Telomeres are specialised nucleoprotein complexes that serve as protective caps
      of linear eukaryotic chromosomes. The loss of the ends of the chromosomes due to
      these un-rejoined double strand breaks (DSBs) may not be lethal to the cell, but
      may instead result in the loss of functional telomeres, chromosome fusions and
      initiation of breakage/fusion/bridge cycle-induced chromosome instability. The
      telomeres also participate in the process of DNA repair, as evidenced by 'de
      novo' synthesis of telomere repeats at DSBs and by the capacity of telomeres to
      binding the essential components of the DNA repair machinery. Based on the
      observation that high-LET radiations efficiently induce chromosome aberrations,
      it was tested whether protons were able to affect telomere structure. Human
      primary fibroblasts (HFFF2) and mouse embryonic fibroblasts (MEFs) were
      irradiated with 4 Gy of 3 MeV protons at the radiobiology facility of the INFN
      LNL. Experiments with X rays were also carried out. Cells were fixed after either
      24 h or 15 d from treatment. A difference in average telomere length, measured by
      quantitative fluorescence in situ hybridisation (Q-FISH), between X rays and
      protons treatment was observed. X rays are able to modify telomere length in
      HFFF2 harvested at a later time. On the other hand, 3 MeV low-energy protons
      induced, both in HFFF2 and in MEFs, a significant increase in telomere length at
      short as well as at long harvesting time periods from treatment. These results
      seem to indicate that lesions characterised by different complexity, as those
      expected after low-energy protons and those induced by damage similar to that
      induced by sparsely ionising radiation, are able to modulate telomere elongation
      at different time periods.

PMID- 17223626
TI  - Epidemiology of invasive candidiasis: a persistent public health problem.
AB  - Invasive candidiasis (IC) is a leading cause of mycosis-associated mortality in
      the United States. We examined data from the National Center for Health
      Statistics and reviewed recent literature in order to update the epidemiology of
      IC. IC-associated mortality has remained stable, at approximately 0.4 deaths per
      100,000 population, since 1997, while mortality associated with invasive
      aspergillosis has continued to decline. Candida albicans remains the predominant
      cause of IC, accounting for over half of all cases, but Candida glabrata has
      emerged as the second most common cause of IC in the United States, and several
      less common Candida species may be emerging, some of which can exhibit resistance
      to triazoles and/or amphotericin B. Crude and attributable rates of mortality due
      to IC remain unacceptably high and unchanged for the past 2 decades.
      Nonpharmacologic preventive strategies should be emphasized, including hand
      hygiene; appropriate use, placement, and care of central venous catheters; and
      prudent use of antimicrobial therapy. Given that delays in appropriate antifungal
      therapy are associated with increased mortality, improved use of early empirical,
      preemptive, and prophylactic therapies should also help reduce IC-associated
      mortality. Several studies have now identified important variables that can be
      used to predict risk of IC and to help guide preventive strategies such as
      antifungal prophylaxis and early empirical therapy. However, improved non-culture
      based diagnostics are needed to expand the potential for preemptive (or early
      directed) therapy. Further research to improve diagnostic, preventive, and
      therapeutic strategies is necessary to reduce the considerable morbidity and
      mortality associated with IC.

PMID- 17223636
TI  - Optimization of doses received by the hospital staff and the members of the
      family of patients undergoing 111In-DTPA-D-Phe1-Octreotide therapy.
AB  - According to the Euratom Directives (96/29, 97/43), the doses received by the
      workers as well as the family of patients and third persons during medical
      exposures, should conform to the dose constraint levels (DCLs), established by
      the authorities for each group in the context of optimisation. This study deals
      with the implementation of a radiation protection protocol, concerning the
      aforementioned group members for patients undergoing treatment with 111In-DTPA-D
      Phe1-Octreotide, after intra-arterial infusion. It is shown that by applying this
      protocol the annual doses to the medical and technical staff are considerably
      reduced and remain below the established DCLs. Following the post-release
      behaviour instructions given to the patient, doses to the family and third
      persons may be kept lower than the corresponding DCLs provided by the National
      Regulations.

PMID- 17223637
TI  - Beta radiation exposure of medical staff and implications for extremity dose
      monitoring.
AB  - Sealed and unsealed beta radiation sources come into use to a greater extent in
      radiation therapy, e.g. for treating inflammatory joint diseases by
      radiosynoviorthesis (RSO), by injecting 90Y, 186Re or 169Er-solutions. Sealed
      90Sr/90Y and 32P-sources or 188Re-liquid-filled balloon catheter are applied in
      vascular brachytherapy. Recently, 90Y-labelled antibodies are being successfully
      used in radioimmunotherapy (RIT) of malign lymphoma. Such practices require
      handling of high activities at small distances to the skin. Thus, the medical
      staff may be exposed to high beta doses. Investigations of the extremity exposure
      were performed at several workplaces, in particular during RSO treatments. The
      local skin dose (LSD), Hp(0,07), was measured with thin-layer TLD (LiF:Mg,P,Cu)
      fixed to the fingers (TLD-tapes). The findings indicate that the exposure of the
      staff can exceed the annual dose limit of 500 mSv when working at low protection
      standard. Routine monitoring of the extremity exposures with ring dosemeters
      appropriate to beta radiation and provided by the approved German dosimetry
      services was found to be needed. But even monitoring with these official 'beta
      dosemeters' does mostly not give suitable results to demonstrate compliance with
      the dose limit. A study was conducted at RSO-workplaces in order reveal a
      correlation between doses measured with ring dosemeters and the maximum LSD
      obtained from the TLD-tapes. The results are discussed and conclusions for
      routine monitoring are drawn.

PMID- 17223638
TI  - Techniques for radiation measurements: microdosimetry and dosimetry.
AB  - Experimental microdosimetry is concerned with the determination of radiation
      quality and how this can be specified in terms of the distribution of energy
      deposition arising from the interaction of a radiation field with a particular
      target site. This paper discusses various techniques that have been developed to
      measure radiation energy deposition over the three orders of magnitude of site
      size; nanometer, micrometer and millimetre, which radiation biology suggests is
      required to fully account for radiation quality. Inevitably, much of the
      discussion will concern the use of tissue-equivalent proportional counters and
      variants of this device, but other technologies that have been studied, or are
      under development, for their potential in experimental microdosimetry are also
      covered. Through an examination of some of the quantities used in radiation
      metrology and dosimetry the natural link with microdosimetric techniques will be
      shown and the particular benefits of using microdosimetric methods for dosimetry
      illustrated.

PMID- 17223639
TI  - Individual and collective doses from cosmic radiation in Ireland.
AB  - This paper assesses the individual and collective doses in Ireland due to cosmic
      radiation. Information on the exposure to cosmic radiation at ground level is
      reviewed and published data on the frequency of routes flown by Irish residents
      is used to calculate the dose due to air travel. Occupational exposure of aircrew
      is also evaluated. Experimental data on cosmic radiation exposure at ground level
      is in good agreement with international estimates and the average individual dose
      is calculated as 300 microSv annually. Published data on international air travel
      by Irish residents shows a 50% increase in the number of flights taken between
      2001 and 2005. This increase is primarily on short-haul flights to Europe, but
      there have been significant percentage increases in all long-haul flights, with
      the exception of flights to Africa. The additional per capita dose due to air
      travel is estimated to be 45 muSv, of which 51% is accumulated on European routes
      and 34% on routes to the United States. Exposure of aircrew to cosmic radiation
      is now controlled by legislation and all airlines holding an Air Operator's
      Certificate issued by the Irish Aviation Authority are required to report
      annually the doses received by their employees in the previous year. There has
      been a 75% increase in the number of aircrew receiving doses >1 mSv since 2002.
      In 2004 and 2005 the average individual doses received by Irish aircrew were 1.8
      and 2.0, mSv, respectively. The corresponding per caput dose for the entire
      population is <3 muSv. While this is low compared with the per caput doses from
      other sources of cosmic radiation, aircrew exposure represents a higher
      collective dose than any other identified group of exposed workers in Ireland.

PMID- 17223640
TI  - Assessment of natural radioactivity and the associated hazards in Iranian cement.
AB  - This paper presents the finding of a study undertaken to determine natural
      radioactivity and associated hazards in local types of cement in Iran. A total of
      42 samples were collected from various manufacturers and suppliers and analysed
      using a shielded HPGe gamma-ray spectrometer. The specific activities of 232Th,
      226Ra and 40K were measured in samples and results ranged from minimum values of
      8, 16, 101 Bq kg(-1) to maximum values of 17, 43 and 141 Bq kg(-1), respectively.
      On the basis of activity concentration index (I), it could be shown that, the
      radioactivity of local cement samples was not greater than the established
      standard values in other countries.

PMID- 17223641
TI  - Application of morphological and physiological parameters representative of a
      Brazilian population sample in the respiratory tract model.
AB  - The human respiratory tract model (HRTM) adopted by ICRP in its Publication 66
      accounts for the morphology and physiology of the respiratory tract. The
      characteristics of air drawn into the lungs and exhaled are greatly influenced by
      the morphology of the respiratory tract, which causes numerous changes in
      pressure, flow rate, direction and humidity as air moves into and out of the
      lungs. These characteristics are important to determine the fractional
      deposition. It is known that the morphology and physiology are influenced by
      environmental, occupational and economic conditions. The ICRP recommends, for a
      reliable evaluation of the regional deposition, the use of parameters from a
      local population wherever such information is available. The main purpose of this
      study is to verify the influence of using the morphology and physiology
      parameters representative of a sample of the Brazilian population on the
      deposition model of the ICRP Publication 66 model.

PMID- 17223642
TI  - Patient dose measurements in diagnostic radiology procedures in Korea.
AB  - This study is the first nationwide investigation aimed at estimating the patient
      dose for radiographic examinations in Korea including gastrointestinal studies,
      computed tomography and mammography. The survey data from 161 hospitals and the
      dose data from 32 hospitals were analysed. The third quartile entrance surface
      dose, dose area product (DAP), weighted CT dose index (CTDIw) and mean glandular
      dose (MGD) were reported. All the estimated doses were less than the stated
      International Atomic Energy Agency (IAEA) reference levels for radiographic
      examinations. However, DAPs for the fluoroscopic examinations had higher dose
      values than the IAEA reference levels. In addition, the CTDIw and MGD were lower
      than the IAEA reference levels.

PMID- 17223643
TI  - Uncertainties in doses calculated according to ICRP recommendations after
      inhalation of 239PUO2 and early chest monitoring.
AB  - This study estimates uncertainties in Pu biokinetics and effective doses
      calculated after an acute inhalation exposure to 239PuO2 according to ICRP
      recommendations (default values for aerosols size and PuO2 dissolution
      parameters). This was performed using the most recently reported variations in
      model parameters and simulations after a Monte Carlo approach. Without chest
      monitoring, uncertainties in thoracic retention and plutonium excretion was 8-10
      (95% confidence interval as the ratio between 97.5 and 2.5 percentiles of the
      lognormal distributions) up to 900 d after exposure. Early chest monitoring
      reduces significantly the uncertainties in plutonium biokinetics and doses which
      remain within a 95% confidence interval of 2.3 as compared with 6.6, without
      monitoring. Analysis of bioassay data previously reported shows that the dose
      delivered to some individuals can be out of the confidence interval, which was
      mostly due to an inhibition of the late mechanical clearance of the alveolar
      interstitium.

PMID- 17223644
TI  - Influence of different dose rates on cell recovery and RBE at different spatial
      positions during protracted conformal radiotherapy.
AB  - The effect of simultaneous induction and repair of sub-lethal lesions during
      protracted irradiation is potentially important for conformal irradiation
      techniques and may influence the relative biological effectiveness (RBE) of
      different radiation qualities. The importance of repair for 50 kV X rays from a
      miniaturised X-ray source producing an essentially isotropic dose distribution
      for intra-operative radiotherapy (IORT) was verified for inactivation of V79
      cells in different distances from the source. The experimental data were
      evaluated in terms of the linear-quadratic model and the generalised Lea
      Catcheside time factor. Furthermore, the shape of survival curves for 14 MeV
      [d(0.25) + T] neutrons at different dose rates implicated a role of repair for
      fast neutrons. Microdosimetric measurements have previously demonstrated
      variations in radiation quality between different positions in a therapy phantom
      for conformal moving-beam therapy with this radiation. Experimental data on the
      effectiveness for inactivation of V79 cells irradiated at such positions are
      presented and the influence of repair is analysed.

PMID- 17223645
TI  - Occupational exposure in nuclear medicine in Portugal in the 1999-2003 period.
AB  - The annual doses received by the staff of nuclear medicine departments from
      public hospitals and private clinics and evaluated by the Individual Monitoring
      Service of the Radiological Protection and Nuclear Safety Department (DPRSN) of
      the Nuclear and Technological Institute (ITN) in Portugal, in the 5 y period from
      1999 to 2003, are analysed and presented in this paper. In the 1999-2003 period,
      ITN-DPRSN monitored on an average 462 workers from nuclear medicine departments,
      which represents 6% of the 8000 workers of the medical field (approximately). The
      medical sector represents 80-85% of all the monitored population in Portugal. The
      professions of the monitored workers at nuclear medicine departments were
      identified by the respective departments as administrative, auxiliary, medical
      doctor, nuclear medicine technician, nurse, pharmacist and physicist. This
      information was collected at the onset of the monitoring and was updated over the
      last 3 y. The annual whole-body doses evaluated in the period 1999-2003 were used
      to derive the distribution of workers by dose intervals for every profession. The
      respective annual average doses and annual collective doses, as well as, the
      total average and total collective doses for the nuclear medicine sector were
      also determined and are presented. Internal radiation hasn't been monitored.

PMID- 17223646
TI  - Carbohydrate-recognition domains of galectin-9 are involved in intermolecular
      interaction with galectin-9 itself and other members of the galectin family.
AB  - Galectin-9 (Gal-9) is a tandem-repeat-type member of the galectin family
      associated with diverse biological processes, such as apoptosis, cell
      aggregation, and eosinophil chemoattraction. Although the detailed sugar-binding
      specificity of Gal-9 has been elucidated, molecular mechanisms that underlie
      these functions remain to be investigated. During the course of our binding study
      by affinity chromatography and surface plasmon resonance (SPR) analysis, we found
      that human Gal-9 interacts with immobilized Gal-9 in the protein-protein
      interaction mode. Interestingly, this intermolecular interaction strongly
      depended on the activity of the carbohydrate recognition domain (CRD), because
      the addition of potent saccharide inhibitors abolished the binding. The presence
      of multimers was also confirmed by Ferguson plot analysis of result of
      polyacrylamide gel electrophoresis and matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS).
      Moreover, this intermolecular interaction was observed between Gal-9 and other
      galectin members, such as Gal-3 and Gal-8, but not Gal-1. Because such properties
      have not been reported yet, they may explain an unidentified mechanism underlying
      the diverse functions of Gal-9.

PMID- 17223647
TI  - Comparison of the methods for profiling glycoprotein glycans--HUPO Human Disease
      Glycomics/Proteome Initiative multi-institutional study.
AB  - Mass spectrometry (MS) of glycoproteins is an emerging field in proteomics,
      poised to meet the technical demand for elucidation of the structural complexity
      and functions of the oligosaccharide components of molecules. Considering the
      divergence of the mass spectrometric methods employed for oligosaccharide
      analysis in recent publications, it is necessary to establish technical standards
      and demonstrate capabilities. In the present study of the Human Proteome
      Organisation (HUPO) Human Disease Glycomics/Proteome Initiative (HGPI), the same
      samples of transferrin and immunoglobulin-G were analyzed for N-linked
      oligosaccharides and their relative abundances in 20 laboratories, and the
      chromatographic and mass spectrometric analysis results were evaluated. In
      general, matrix-assisted laser desorption/ionization (MALDI) time-of-flight MS of
      permethylated oligosaccharide mixtures carried out in six laboratories yielded
      good quantitation, and the results can be correlated to those of chromatography
      of reductive amination derivatives. For underivatized oligosaccharide alditols,
      graphitized carbon-liquid chromatography (LC)/electrospray ionization (ESI) MS
      detecting deprotonated molecules in the negative ion mode provided acceptable
      quantitation. The variance of the results among these three methods was small.
      Detailed analyses of tryptic glycopeptides employing either nano LC/ESI MS/MS or
      MALDI MS demonstrated excellent capability to determine site-specific or subclass
      specific glycan profiles in these samples. Taking into account the variety of MS
      technologies and options for distinct protocols used in this study, the results
      of this multi-institutional study indicate that MS-based analysis appears as the
      efficient method for identification and quantitation of oligosaccharides in
      glycomic studies and endorse the power of MS for glycopeptide characterization
      with high sensitivity in proteomic programs.

PMID- 17223648
TI  - Structure and role of sialic acids on the surface of Aspergillus fumigatus
      conidiospores.
AB  - Aspergillus fumigatus is an opportunistic fungal pathogen that causes a life
      threatening invasive fungal disease (invasive aspergillosis, IA) in
      immunocompromised individuals. The first step of pathogenesis is thought to be
      the attachment of conidia to proteins in lung tissue. Previous studies in our
      laboratory have shown that conidia adhere to basal lamina proteins via negatively
      charged sugars on their surface, presumably sialic acids. Sialic acids are a
      family of more than 50 substituted derivatives of a nine-carbon monosaccharide,
      neuraminic acid. The purpose of this study was 2-fold: (1) to determine the
      structure of sialic acids and the glycan acceptor on A. fumigatus
      oligosaccharides and (2) to determine the effect on the removal of sialic acids
      from conidia on conidial binding to the extracellular matrix protein fibronectin
      and phagocytosis of conidia by cultured macrophages and type 2 pneumocytes.
      Surface sialic acids were removed using Micromonospora viridifaciens sialidase or
      using acetic acid, mild acid hydrolysis. Lectin binding studies revealed that the
      majority of conidial sialic acids are alpha2,6-linked to a galactose residue.
      High-pressure liquid chromatography of derivatized sialic acids released from
      conidia revealed that unsubstituted N-acetylneuraminic acid is the predominant
      sialic acid on the surface of conidia. Enzymatic removal of sialic acid
      significantly decreased the binding of conidia to fibronectin by greater than 65%
      when compared with sham-treated controls. In addition, removal of sialic acids
      decreased conidial uptake by cultured murine macrophages and Type 2 pneumocytes
      by 33% and 53%, respectively. Hence, sialylated molecules on A. fumigatus conidia
      are ligands for both professional and nonprofessional phagocytes.

PMID- 17223649
TI  - The fabrication and application of Zernike electrostatic phase plate.
AB  - The Zernike electrostatic phase plate (ZEPP) consisting of three ring electrodes
      and two insulating rings has been fabricated using Micro Electro-Mechanical
      System processes. The electrostatic field produced in the phase plate was
      measured by electrostatic force microscopy. The electrostatic field and focal
      length of the phase plate is calculated using electron optics principles. The
      comparison of the experimental electrostatic field and the theoretical calculated
      is discussed. Finally, we report the application of ZEPP to enhance contrast of
      the SiON(x)/SiO(2) interface in an NMOS semiconductor device. The quantitative
      analysis of the contrast enhancement versus the applied bias is discussed in
      detail.

PMID- 17223650
TI  - Electron holography on dynamic motion of secondary electrons around sciatic nerve
      tissues.
AB  - By means of electron holographic visualization of detailed electric potential
      distribution around sciatic nerve tissues coated with C and OsO(4), we show that
      the steady state of these specimens subjected to intense charging with electron
      irradiation is accompanied with a dynamic motion of collective secondary
      electrons; the secondary electrons emitted from the coated specimens revolve
      around the positively charged specimens forming stationary orbits. Further, this
      study clarified the possibility of the direct visualization of a part of the
      orbits of the collective secondary electrons without disturbing their motions.

PMID- 17223651
TI  - Characterisation of a dendritic cell subset in synovial tissue which strongly
      expresses Jak/STAT transcription factors from patients with rheumatoid arthritis.
AB  - OBJECTIVES: To characterise the phenotype of the putative dendritic cells
      strongly expressing Jak3 and STAT4, which have been previously identified in the
      synovial tissue of patients with active rheumatoid arthritis (RA). METHODS:
      Synovial biopsy specimens were obtained at arthroscopy from 30 patients with
      active RA (42 synovial biopsies). Immunohistological analysis was performed using
      monoclonal antibodies to detect dendritic cell subsets, including activation
      markers and cytokines relevant to dendritic cell function. Co-localisation of
      cell surface markers and cytokines was assessed primarily using sequential
      sections, with results confirmed by dual immunohistochemistry and
      immunofluorescence with confocal microscopy. RESULTS: The dendritic cells
      identified in RA synovial tissue that strongly express Jak3 also strongly express
      STAT4 and STAT 6 and are correlated with the presence of serum rheumatoid factor.
      These cells are not confined to a single dendritic cell subset, with cells having
      phenotypes consistent with both myeloid- and plasmacytoid-type dendritic cells.
      The activation status of these dendritic cells suggests that they are maturing or
      mature dendritic cells. These dendritic cells produce IL12 as well as interferon
      alpha and gamma. CONCLUSIONS: The close correlation of these dendritic cells with
      the presence of serum rheumatoid factor, a prognostic factor for worse disease
      outcome, and the strong expression by these cells of components of the Jak/STAT
      transcription factor pathway suggest a potential therapeutic target for the
      treatment of RA.

PMID- 17223652
TI  - Anti-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals
      induction of novel pro-inflammatory genes potentially involved in primary
      antiphospholipid syndrome.
AB  - OBJECTIVE: To determine the effects of primary antiphospholipid syndrome (PAPS)
      derived anti-beta(2)GPI antibodies on gene expression in human umbilical vein
      endothelial cells (HUVEC) by gene profiling using microarrays. METHODS: Anti
      beta(2)GPI antibodies purified from sera of patients with PAPS or control IgG
      isolated from normal subjects were incubated with HUVEC for 4 h before isolation
      of RNA and processing for hybridisation to Affymetrix Human Genome U133A-2.0
      arrays. Data were analysed using a combination of the MAS 5.0 (Affymetrix) and
      GeneSpring (Agilent) software programmes. For selected genes microarray data were
      confirmed by real-time PCR analysis or at the protein level by ELISA. RESULTS: A
      total of 101 genes were found to be upregulated and 14 genes were downregulated
      twofold or more in response to anti-beta(2)GPI antibodies. A number of novel
      genes not previously associated with APS were induced, including chemokines
      CCL20, CXCL3, CX3CL1, CXCL5, CXCL2 and CXCL1, the receptors Tenascin C, OLR1, IL
      18 receptor 1, and growth factors CSF2, CSF3 IL-6, IL1beta and FGF18. The
      majority of downregulated genes were transcription factors/signalling molecules
      including ID2. Quantitative real-time RT-PCR analysis confirmed the microarray
      results for selected genes (CSF3, CX3CL1, FGF18, ID2, SOD2, Tenascin C).
      CONCLUSIONS: This study reveals a complex gene expression response in HUVEC to
      anti-beta(2)GPI antibodies with multiple chemokines, pro-inflammatory cytokines,
      pro-thrombotic and pro-adhesive genes regulated by these antibodies in vitro.
      Some of these newly identified anti-beta(2)GPI antibody-regulated genes could
      contribute to the vasculopathy associated with this disease.

PMID- 17223653
TI  - Catastrophic antiphospholipid syndrome during pregnancy and puerperium: maternal
      and fetal characteristics of 15 cases.
AB  - BACKGROUND: The catastrophic variant of the antiphospholipid syndrome (APS) is a
      life-threatening form of presentation of this syndrome that can be triggered by
      several factors. AIM: To describe the characteristics of patients who developed
      catastrophic APS triggered during pregnancy and puerperium. METHODS: A review of
      the first 255 cases collected in the website-based "CAPS Registry" was
      undertaken. Three new and unpublished cases of catastrophic APS developed during
      pregnancy and puerperium were added. RESULTS: Fifteen cases were identified. The
      mean (range) age was 27 (17-38) years. Most patients had a previous unsuccessful
      obstetric history. In 7 of 14 (50%) cases with available medical history, the
      catastrophic APS appeared during pregnancy, in 6 (43%) during the puerperium and
      in 1 (7%) after curettage for a fetal death. The main clinical and serological
      characteristics were similar to those patients with catastrophic APS triggered by
      other factors, except for a history of a higher prevalence of previous abortions
      (p<0.01). Several specific features were found, including the HELLP (haemolysis,
      elevated liver enzymes, low platelets) syndrome in 8 (53%) patients, placental
      infarctions in 4 (27%) patients, and pelvic vein thrombosis and myometrium
      thrombotic microangiopathy in 1 (7%) patient each. Mortality rate was high for
      the mothers (46%), and for the babies (54%). CONCLUSIONS: It is important to
      consider the possibility of the development of catastrophic APS in those patients
      with signs of HELLP syndrome and multiorgan failure during pregnancy or
      puerperium, especially in those patients with previous history of abortions
      and/or thrombosis.

PMID- 17223654
TI  - Ectopic lymphoid neogenesis in psoriatic arthritis.
AB  - BACKGROUND: Ectopic lymphoid neogenesis (LN) occurs in rheumatoid synovium, where
      it is thought to drive local antigen-dependent B cell development and
      autoantibody production. This process involves the expression of specific homing
      chemokines and the development of high endothelial venules (HEV). OBJECTIVE: To
      investigate whether these mechanisms occur in psoriatic arthritis (PsA) synovium,
      where autoantibodies have not been described and the organisation and function of
      B cells is not clear, and to analyse their clinical correlates. METHODS:
      Arthroscopic synovial biopsy specimens from patients with PsA before and after
      tumour necrosis factor alpha blockade were characterised by immunohistochemical
      analysis for T/B cell segregation, peripheral lymph node addressin (PNAd)
      positive HEV, and the expression of CXCL13, CCL21 and CXCL12 chemokines in
      relation to the size of lymphoid aggregates. RESULTS: Lymphoid aggregates of
      variable sizes were observed in 25 of 27 PsA synovial tissues. T/B cell
      segregation was often observed, and was correlated with the size of lymphoid
      aggregates. A close relationship between the presence of large and highly
      organised aggregates, the development of PNAd+ HEV, and the expression of CXCL13
      and CCL21 was found. Large organised aggregates with all LN features were found
      in 13 of 27 tissues. LN in PsA synovitis was not related to the duration, pattern
      or severity of the disease. The synovial LN pattern remained stable over time in
      persistent synovitis, but a complete response to treatment was associated with a
      regression of the LN features. CONCLUSIONS: LN occurs frequently in inflamed PsA
      synovial tissues. Highly organised follicles display the characteristic features
      of PNAd+ HEV and CXCL13 and CCL21 expression, demonstrating that the
      microanatomical bases for germinal centre formation are present in PsA. The
      regression of LN on effective treatment indicates that the pathogenic and
      clinical relevance of these structures in PsA merits further investigation.

PMID- 17223655
TI  - The intra-articular distribution of 90yttrium does not influence the clinical
      outcome of radiation synovectomy of the knee.
AB  - OBJECTIVES: To assess the impact of the intra-articular distribution of
      (90)yttrium-citrate ((90)Y) on the clinical effect of radiosynoviorthesis (RSO)
      of the knee and on (90)Y leakage from this joint. METHODS: Patients with
      arthritis of the knee received 185 MBq (90)Y combined with a glucocorticoid,
      followed by clinical bed rest. Intra-articular (90)Y distribution, measured with
      a dual-head gamma camera immediately or after 24 hours, was scored as mainly
      diffuse or mainly focal. Leakage to regional lymph nodes, the liver and spleen
      was assessed with a dual-head gamma camera after 24 hours. Clinical effect was
      scored after 6 months by a composite change index (CCI), range 0-12; responders
      were defined as having a CCI > or =6. RESULTS: Seventy-eight knees of 69
      patients, mostly suffering from undifferentiated arthritis (42%) or RA (28%),
      were treated. (90)Y distribution was mainly diffuse in 54% and mainly focal in
      46% with clinical response rates of 40% versus 56%, respectively, p = 0.3. CCI
      was not correlated with distribution. (90)Y leakage was found only to the liver
      and the spleen (mean leakage 0.4% and 1.1%, respectively). Leakage was
      significantly less in case of diffuse intra-articular (90)Y distribution, whereas
      leakage to the liver was correlated with distribution (r = 0.68, p<0.001). (90)Y
      leakage was not correlated with CCI. CONCLUSIONS: Intra-articular (90)Y
      distribution does not influence the clinical effect of RSO of the knee. Although
      (90)Y leakage from the joint is less if (90)Y distributes diffusely in the joint
      cavity, leakage does not seem to hamper the clinical effect.

PMID- 17223656
TI  - Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood
      cells: assignment of a type I interferon signature in a subpopulation of
      patients.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a heterogeneous disease with unknown
      cause. AIM: To identify peripheral blood (PB) gene expression profiles that may
      distinguish RA subtypes. METHODS: Large-scale expression profiling by cDNA
      microarrays was performed on PB from 35 patients and 15 healthy individuals.
      Differential gene expression was analysed by significance analysis of microarrays
      (SAM), followed by gene ontology analysis of the significant genes. Gene set
      enrichment analysis was applied to identify pathways relevant to disease.
      RESULTS: A substantially raised expression of a spectrum of genes involved in
      immune defence was found in the PB of patients with RA compared with healthy
      individuals. SAM analysis revealed a highly significant elevated expression of
      interferon (IFN) type I regulated genes in patients with RA compared with healthy
      individuals, which was confirmed by gene ontology and pathway analysis,
      suggesting that this pathway was activated systemically in RA. A quantitative
      analysis revealed that increased expression of IFN-response genes was
      characteristic of approximately half of the patients (IFN(high) patients).
      Application of pathway analysis revealed that the IFN(high) group was largely
      different from the controls, with evidence for upregulated pathways involved in
      coagulation and complement cascades, and fatty acid metabolism, while the
      IFN(low) group was similar to the controls. CONCLUSION: The IFN type I signature
      defines a subgroup of patients with RA, with a distinct biomolecular phenotype,
      characterised by increased activity of the innate defence system, coagulation and
      complement cascades, and fatty acid metabolism.

PMID- 17223658
TI  - Effects of intra-articular corticosteroids and anti-TNF therapy on neutrophil
      activation in rheumatoid arthritis.
AB  - OBJECTIVE: The pro-inflammatory calcium-binding protein S100A12 has been recently
      ascribed to the novel group of damage associated molecular pattern (DAMP)
      molecules. Serum levels of S100A12 reflect neutrophil activation during synovial
      inflammation. The aim of this project was to analyse the effect of intra
      articular corticosteroids or systemic anti-TNF treatment on synovial expression
      and serum levels of S100A12 in rheumatoid arthritis (RA). METHODS: Serum and
      synovial tissue was obtained from 19 RA patients prior to and 2 weeks after intra
      articular corticosteroid therapy. Serum was collected for 34 other patients, and
      in 14 of these patients synovial tissue was additionally obtained prior to and
      after 8 weeks of infliximab treatment. The expression of S100A12 was analysed by
      immunohistochemistry on frozen sections. Levels of S100A12 in serum were
      determined by ELISA. RESULTS: S100A12 serum levels were elevated in patients with
      active RA prior to therapy and decreased significantly in patients who responded
      to treatment in both patient groups, but not in non-responders. The synovial
      expression of S100A12 was reduced 2 weeks after successful intra-articular
      corticosteroid treatment. A similar decrease in local expression was found after
      8 weeks of successful infliximab treatment. CONCLUSIONS: Successful treatment of
      RA leads to downregulation of the DAMP protein S100A12. Expression and secretion
      of S100A12 is rapidly diminished after therapy with intra-articular
      corticosteroids or infliximab. Taking these findings together, decreasing serum
      concentrations of S100A12 could reflect alleviated synovial neutrophil activation
      during successful anti-inflammatory therapy in RA.

PMID- 17223657
TI  - Safety and efficacy of leflunomide in primary Sjogren's syndrome: a phase II
      pilot study.
AB  - BACKGROUND: For invalidating symptoms in primary Sjogren's syndrome (pSS), there
      is still a need for easy-to-administer, cost-effective and well-tolerated
      systemic treatment. Leflunomide (LEF) is structurally unrelated to other
      immunomodulatory drugs and might be efficacious in pSS, given its characteristic
      immunoregulatory modes of action. OBJECTIVE: To investigate the safety and
      efficacy of LEF in pSS in a phase II open-label pilot study. METHODS: 15 patients
      with pSS with early and active disease received LEF 20 mg once daily for 24
      weeks. Tolerability, safety and efficacy of LEF were evaluated every 8 weeks.
      Additional safety visits were performed every fortnight. RESULTS: Mild
      gastrointestinal discomfort (including diarrhoea) and hair loss were mainly
      reported. Five patients developed lupus-like skin lesions on the face, arms or
      trunk, responding well to topical corticosteroids, nevertheless causing the
      withdrawal of one patient. Two patients with pre-existing hypertension had to
      increase dosages of anti-hypertensive drugs. Increased levels of alanine
      aminotransferase normalised after dose reduction in two patients. A decrease in
      general fatigue and an increase in physical functioning were observed after 24
      weeks. Serum IgG levels decreased from 8 weeks onwards. Schirmer test values
      increased, not reaching statistical significance, whereas sialometry values did
      not change. In four of five repeated biopsies, the lymphocytic focus score
      decreased at the rate of 1 focus/4 mm(2). A remarkable amelioration of
      leucocytoclastic vasculitis was observed in three patients. CONCLUSIONS: Although
      the safety profile seems fairly acceptable, the observed indications for efficacy
      were modest and may be doubtful in justifying a randomised controlled trial of
      LEF in pSS.

PMID- 17223659
TI  - Reliability of the ICF Core Set for rheumatoid arthritis.
AB  - BACKGROUND: The comprehensive ICF Core Set for rheumatoid arthritis (RA) is a
      selection of 96 categories from the International Classification of Functioning,
      Disability and Health (ICF), representing relevant aspects in the functioning of
      RA patients. OBJECTIVES: To study the reliability of the ICF Core Set for RA in
      rheumatological practice, and to explore the metric of the qualifiers' scale.
      METHODS: 25 RA patients from an outpatient department of rheumatology were
      interviewed using the ICF Core Set for RA (76% females, mean (SD) age 57.5 (12.5)
      years, disease duration 15.9 (14.6) years). Interviews were performed
      independently by both a physiotherapist and an occupational therapist on the same
      day and again after one week by one of them. The severity of the patients'
      problems was quantified on a qualifier scale ranging from 0 (no problem) to 4
      (complete problem). Analyses of intra-rater and inter-rater agreement, kappa
      statistics, and Rasch analyses were applied. RESULTS: Mean intra-rater (inter
      rater) complete agreement for all categories was seen in 59% (47%) of
      observations, ranging from 29% (0%) to 96% (80%) for individual categories.
      Weighted kappa statistics with value > or =0.4 showed reliability in 86% of
      categories within raters, and in 43% of categories between raters. Improved inter
      rater and intra-rater reliability was observed with a reduced number of
      qualifiers for the categories. CONCLUSIONS: Inter-rater and intra-rater
      reliability of the ICF Core Set of RA was low to moderate. The metric of the
      qualifiers' scale may be improved by reducing the number of qualifiers to three
      for all components.

PMID- 17223660
TI  - HLA-Cw6 and HLA-DRB1*07 together are associated with less severe joint disease in
      psoriatic arthritis.
AB  - BACKGROUND: Human leucocyte antigen (HLA) genes predict disease severity in
      psoriasis (HLA-Cw6) and rheumatoid arthritis (shared epitope (SE)), but the
      situation is unclear for psoriatic arthritis (PsA). AIM: To determine the
      association of the HLA-Cw6 and HLA-DRB1 gene with disease severity in a large UK
      cohort with PsA. METHODS: Genotyping of the HLA-Cw and HLA-DRB1 loci was
      undertaken in DNA samples from patients with PsA (n = 480). Stratification and
      regression analysis were used within the PsA cases to determine whether HLA-Cw6,
      HLA-DRB1 or the presence of the SE alleles predicted disease severity as measured
      by the Health Assessment Questionnaire score, the total number of damaged or
      involved joints adjusted for disease duration and disease-modifying antirheumatic
      treatments. RESULTS: HLA-Cw6 was found to be in linkage disequilibrium with HLA
      DRB1*07 (r(2) = 0.46). Patients with PsA who carried both HLA-Cw6 and HLA-DRB1*07
      had fewer damaged or involved joints (41% fewer damaged (95% CI 23% to 55%, p =
      0.02) and 31% fewer involved joints (95% CI 16% to 44%, p<0.001)) compared with
      those who carried neither HLA-Cw6 nor HLA-DRB1*07 alleles. Those who carried
      either HLA-Cw6 or HLA-DRB1*07 alleles alone had no evidence of a reduction in
      joint involvement. The SE, HLA-DRB1*03 and HLA-DRB1*04 alleles did not predict
      severity using these outcome measures. CONCLUSION: Patients with PsA carrying
      both HLA-Cw6 and HLA-DRB1*07 alleles have a less severe course of arthritis. This
      suggests that a protective locus lies on a haplotype marked by these alleles. No
      association was detected with disease severity and SE status.

PMID- 17223661
TI  - Predominant activation of MAP kinases and pro-destructive/pro-inflammatory
      features by TNF alpha in early-passage synovial fibroblasts via TNF receptor-1:
      failure of p38 inhibition to suppress matrix metalloproteinase-1 in rheumatoid
      arthritis.
AB  - OBJECTIVE: To examine the relative importance of tumour necrosis factor-receptor
      1 (TNF-R1) and TNF-R2 and their signalling pathways for pro-inflammatory and pro
      destructive features of early-passage synovial fibroblasts (SFB) from rheumatoid
      arthritis (RA) and osteoarthritis (OA). METHODS: Cells were stimulated with
      tumour necrosis factor (TNF)alpha or agonistic anti-TNF-R1/TNF-R2 monoclonal
      antibodies. Phosphorylation of p38, ERK and JNK kinases was assessed by western
      blot; proliferation by bromodesoxyuridine incorporation; interleukin (IL)6, IL8,
      prostaglandin E(2) (PGE(2)) and matrix metalloproteinase (MMP)-1 secretion by
      ELISA; and MMP-3 secretion by western blot. Functional assays were performed with
      or without inhibition of p38 (SB203580), ERK (U0126) or JNK (SP600125). RESULTS:
      In RA- and OA-SFB, TNFalpha-induced phosphorylation of p38, ERK or JNK was
      exclusively mediated by TNF-R1. Reduction of proliferation and induction of IL6,
      IL8 and MMP-1 were solely mediated by TNF-R1, whereas PGE(2) and MMP-3 secretion
      was mediated by both TNF-Rs. In general, inhibition of ERK or JNK did not
      significantly alter the TNFalpha influence on these effector molecules. In
      contrast, inhibition of p38 reversed TNFalpha effects on proliferation and
      IL6/PGE(2) secretion (but not on IL8 and MMP-3 secretion). The above effects were
      comparable in RA- and OA-SFB, except that TNFalpha-induced MMP-1 secretion was
      reversed by p38 inhibition only in OA-SFB. CONCLUSION: In early-passage RA/OA
      SFB, activation of MAPK cascades and pro-inflammatory/pro-destructive features by
      TNFalpha is predominantly mediated by TNF-R1 and, for proliferation and
      IL6/PGE(2) secretion, exclusively regulated by p38. Strikingly, RA-SFB are
      insensitive to p38 inhibition of MMP-1 secretion. This indicates a resistance of
      RA-SFB to the inhibition of pro-destructive functions and suggests underlying
      structural/functional alterations of the p38 pathway, which may contribute to the
      pathogenesis or therapeutic sensitivity of RA, or both.

PMID- 17223662
TI  - Ex vivo interleukin 1 receptor antagonist production on lipopolysaccharide
      stimulation is associated with rheumatoid arthritis and with joint damage.
AB  - OBJECTIVES: (1) To assess innate ex vivo production of interleukin 1beta
      (IL1beta) and interleukin 1 receptor antagonist (IL1Ra) in patients with recent
      onset rheumatoid arthritis (RA) as compared with healthy controls; (2) to assess
      the association of ex vivo IL1beta and IL1Ra production with progression of joint
      damage in RA; (3) to determine whether differences in ex vivo IL1beta production
      are explained by distribution of the IL1beta single nucleotide polymorphism C
      511T. METHODS: Levels of IL1beta and IL1Ra (measured by ELISA after whole-blood
      stimulation with lipopolysaccharide) and distribution of IL1beta C-511T were
      compared in 76 patients with recent-onset RA who had received no disease
      modifying antirheumatic drugs (DMARDs), and 63 healthy controls. ORs for RA based
      on ex vivo IL1beta and IL1Ra production were calculated. Association of ex vivo
      IL1beta and IL1Ra production with progression of joint damage (Sharp-van der
      Heijde score over 2 years) was determined by linear regression with correction
      for baseline characteristics. RESULTS: Patients with recent-onset RA showed lower
      ex vivo IL1beta and higher ex vivo IL1Ra production than healthy controls
      (p<0.001), with ORs for RA of 2.4 (95% CI 1.2 to 4.9) for low IL1beta-producers
      and 7.6 (95% CI 3.2 to 18.0) for high IL1Ra-producers. High ex vivo IL1Ra
      production was associated with progression of joint damage (p = 0.01). The
      IL1beta C-511T genotype distribution was not significantly different between
      patients and controls. CONCLUSIONS: Patients with recent-onset RA had decreased
      ex vivo IL1beta production and increased ex vivo IL1Ra production compared with
      controls. Ex vivo IL1Ra production is an independent predictor of progression of
      joint damage in recent-onset RA.

PMID- 17223663
TI  - Time required for disappearance of urate crystals from synovial fluid after
      successful hypouricaemic treatment relates to the duration of gout.
AB  - OBJECTIVES: To determine whether hypouricaemic treatment results in the
      disappearance of urate crystals from gouty joints and to define the time
      required. METHODS: In 18 patients with monosodium urate (MSU) crystal proven
      gout, and after the initiation of successful serum uric acid (SUA)-lowering
      treatment, an arthrocentesis of the asymptomatic signal joint (11 knees, 7 first
      metatarsophalangeal joints) was performed every 3 months to obtain a synovial
      fluid (SF) sample. The sample was then analysed for the presence of MSU crystals,
      and the number of crystals/400x field was noted. SUA levels and the duration of
      gout were also noted. RESULTS: MSU crystals disappeared from the SF of all 18
      joints after reduction of SUA to normal levels. The time required for
      disappearance ranged from 3 to 33 months; disappearance time correlated with the
      duration of gout (r(s) = 0.71; p<0.01). The median number of MSU crystals in the
      SF samples before urate-lowering treatment was 7.5 (2.5-11) crystals/400x field,
      reducing to 3 (1-6.5) crystals/400x field (p<0.05) at 3 months. Crystal counts
      continued to decrease after 3 months. CONCLUSIONS: In gout, reduction of SUA to
      normal levels results in disappearance of urate crystals from SF, requiring a
      longer time in those patients with gout of longer duration. This indicates that
      urate crystal deposition in joints is reversible. Normalisation of SUA levels
      results in a decrease in the concentration of MSU crystals in SF in the
      asymptomatic gouty joints. This may partially explain the reduced frequency of
      gouty attacks when a patient has been treated with SUA-lowering drugs.

PMID- 17223664
TI  - Management of septic arthritis: a systematic review.
AB  - OBJECTIVE: To evaluate the existing evidence on the diagnosis and management of
      septic arthritis in native joints. DESIGN: Systematic review. DATA SOURCES:
      Cochrane Library, Medline, Embase, National Electronic Library for Health,
      reference lists, national experts. REVIEW METHODS: Systematic review of the
      literature with evaluation of the methodological quality of the selected papers
      using defined criteria set out by the Clinical Effectiveness and Evaluation Unit
      of the Royal College of Physicians. RESULTS: 3291 citations were initially
      identified. Of these, 189 full text articles were identified for potential
      selection. Following review of these full text articles, 80 articles were found
      to fulfil the inclusion criteria and were included in the final list.
      CONCLUSIONS: were drawn on the diagnosis, investigation and management of septic
      arthritis. DISCUSSION: Little good quality evidence exists to guide the diagnosis
      and management of septic arthritis. Overall, no investigation is more reliable in
      the diagnosis of septic arthritis than the opinion of an experienced doctor.
      Aspiration and culture of synovial fluid is crucial to the diagnosis, but
      measurement of cell count is unhelpful. Antibiotics are clearly required for a
      prolonged period, but there are no data to indicate by which route or for how
      long. Key unanswered questions remain surrounding the medical and surgical
      management of the infected joint.

PMID- 17223665
TI  - The glomerular filtration rate in an apparently healthy population and its
      relation with cardiovascular mortality during 10 years.
AB  - AIMS: Moderate-to-severe chronic renal failure is an established risk factor for
      cardiovascular disease and mortality. However, most studies have been performed
      in selected populations and the impact of very small decrements of renal function
      on long-term cardiac morbidity and mortality has not yet been established. Also,
      the cut-off level of glomerular filtration rate (GFR) from which cardiovascular
      risk increases has not exactly been established. This study wants to address
      these questions. METHODS AND RESULTS: Ten year follow-up of a representative
      population-based cohort comprised 8913 randomly selected, apparently healthy
      participants. Participants were randomly drawn from Belgian voting lists.
      Cardiovascular risk factors were noted. Serum creatinine values were corrected to
      isotope dilution mass spectrometry standard, and GFR was calculated using the
      recently modified 'modification of diet in renal disease' equation. Participants
      were followed for 10 years, and cause-specific death was registered by analysis
      of death certificates. The probability to die from all causes or from
      cardiovascular causes during the 10 year follow-up period increased in each
      quartile of GFR, even after correction for different other comorbid conditions.
      CONCLUSION: Even mild renal failure is an independent risk factor for
      cardiovascular mortality within 10 years in an apparently healthy unselected
      population. This detrimental effect starts already at a relatively high GFR of 90
      mL/min/1.73 m2 and remains present after correction for other established
      cardiovascular risk factors.

PMID- 17223666
TI  - Adiponectin and risk of acute coronary syndromes: defining the obesity phenotype.

PMID- 17223667
TI  - Side effects and complications. Hope for healthier hearts.

PMID- 17223668
TI  - Side effects and complications. Does switching therapy away from d4T help the
      face?

PMID- 17223669
TI  - Side effects and complications.  Creatine flunks a test.

PMID- 17223670
TI  - Side effects and complications. Uridine finally gets tested in people.

PMID- 17223671
TI  - Aristotle's biopolitics: a defense of biological teleology against biological
      nihilism.
AB  - Modern Darwinian biology seems to promote nihilism, for it seems to teach that
      there is no rationally discoverable standard in nature for giving meaning to
      life. The purpose of this article is to argue for a revival of Aristotle's
      biological teleology as a reasonable alternative to biological nihilism. The
      article begins with Edward Wilson's vain struggle against nihilism. Then it is
      argued that a teleological understanding of nature is assumed in the practice of
      medicine, as illustrated by one case from Oliver Sacks' neurological practice.
      The article then considers the importance of biological teleology for Aristotle's
      moral and political philosophy, and attention is given to some points of
      agreement and disagreement with contemporary sociobiologists. The main part of
      the article is then devoted to a defense of Aristotle's biology against the five
      objections that might be made by a Darwinian biologist. Finally, the article
      illustrates the practical implications of this issue for bioethics by considering
      the recent work of Engelhardt.

PMID- 17223672
TI  - Aristotelian teleology and Aristotelian reason: a commentary.

PMID- 17223673
TI  - History and biological teleology.

PMID- 17223674
TI  - On the relevance of Aristotle's bioethics.

PMID- 17223676
TI  - Aristotle and the sociobiologists: an old controversy revived.

PMID- 17223675
TI  - Biological nihilism and modern moral and political theory.

PMID- 17223677
TI  - Human nature and morality: a sociobiological perspective.

PMID- 17223678
TI  - Final causes and instant cases: a comment.

PMID- 17223679
TI  - On the problematic dimensions of bioethics and the pre-conditions of natural
      right.

PMID- 17223680
TI  - The good life and the life sciences.

PMID- 17223681
TI  - Ethical issues in transfusion medicine.
AB  - The practice of transfusion medicine involves a number of ethical issues because
      blood comes from human beings and is a precious resource with a limited shelf
      life. In 1980 the International Society of Blood Transfusion endorsed its first
      formal code of ethics, which was adopted by the World Health Organisation and the
      League of Red Crescent Societies. A revised code of ethics for donation and
      transfusion was endorsed in 2000. Blood donation as a gift, donor
      confidentiality, donor notification and donor consent, consent for transfusion,
      the right to refuse blood transfusion, the right to be informed if harmed, and
      ethical principles for establishments, are discussed in the international and
      Indian contexts.

PMID- 17223682
TI  - The cloning controversy.
AB  - Stem cell research has captured the imagination of many, including the scientific
      and medical community. But the medical community received a wake-up call early
      this year when a well-known researcher publicly confessed to deception. While the
      core question relates to honesty and integrity, it is equally necessary to
      examine the system that made such deception possible.

PMID- 17223683
TI  - Interventions in reproduction.
AB  - Assisted reproductive technology has helped many childless couples. It has also
      raised questions about how appropriate the technology might be in different
      situations. How we understand parenthood is crucial in taking a stand on such
      scientific intervention. It is suggested that physicians should decide on
      offering artificial insemination, surrogacy and in-vitro fertilisation only after
      considering if the child will have good parents and if there will be legal
      complications from the use of the technology.

PMID- 17223684
TI  - Catalytic mechanism of a MYST family histone acetyltransferase.
AB  - Distinct catalytic mechanisms have been proposed for the Gcn5 and MYST histone
      acetyltransferase (HAT) families. Gcn5-like HATs utilize an ordered sequential
      mechanism involving direct nucleophilic attack of the N-epsilon-lysine on the
      enzyme-bound acetyl-CoA. Recently, MYST enzymes were reported to employ a ping
      pong route of catalysis via an acetyl-cysteine intermediate. Here, using the
      prototypical MYST family member Esa1, and its physiological complex (piccolo
      NuA4), steady-state kinetic analyses revealed a kinetic mechanism that requires
      the formation of a ternary complex prior to catalysis, where acetyl-CoA binds
      first and CoA is the last product released. In the absence of histone acceptor,
      slow rates of enzyme auto-acetylation (7 x 10(-4) s(-1), or approximately 2500
      fold slower than histone acetylation; kcat = 1.6 s(-1)) and of CoA formation
      (0.0021 s(-1)) were inconsistent with a kinetically competent acetyl-enzyme
      intermediate. Previously, Cys-304 of Esa1 was the proposed nucleophile that forms
      an acetyl-cysteine intermediate. Here, mutation of this cysteine (C304A) in Esa1
      or within the piccolo NuA4 complex yielded an enzyme that was catalytically
      indistinguishable from the wild type. Similarly, a pH rate (kcat) analysis of the
      wild type and C304A revealed an ionization (pKa = 7.6-7.8) that must be
      unprotonated. Mutation of a conserved active-site glutamate (E338Q) reduced kcat
      approximately 200-fold at pH 7.5; however, at higher pH, E338Q exhibited nearly
      wild-type activity. These data are consistent with Glu-338 (general base)
      activating the N-epsilon-lysine by deprotonation. Together, the results suggest
      that MYST family HATs utilize a direct-attack mechanism within an Esa1 x acetyl
      CoA x histone ternary complex.

PMID- 17223686
TI  - Mechanism of the kinetically-controlled folding reaction of subtilisin.
AB  - Like many secreted proteases, subtilisin is kinetically stable in the mature form
      but unable to fold without assistance from its prodomain. The existence of high
      kinetic barriers to folding challenges many widely accepted ideas, namely, the
      thermodynamic determination of native structure and the sufficiency of
      thermodynamic stability to determine a pathway. The purpose of this article is to
      elucidate the physical nature of the kinetic barriers to subtilisin folding and
      to show how the prodomain overcomes these barriers. To address these questions,
      we have studied the bimolecular folding reaction of the subtilisin prodomain and
      a series of subtilisin mutants, which were designed to explore the steps in the
      folding reaction. Our analysis shows that inordinately slow folding of the mature
      form of subtilisin results from the accrued effects of two slow and sequential
      processes: (1) the formation of an unstable and topologically challenged
      intermediate and (2) the proline-limited isomerization of the intermediate to the
      native state. The low stability of nascent folding intermediates results in part
      from subtilisin's high dependence on metal binding for stability. Native
      subtilisin is thermodynamically unstable in the absence of bound metals. Because
      the two metal binding sites are formed late in folding, however, they contribute
      little to the stability of folding intermediates. The formation of productive
      folding intermediates is further hindered by the topological challenge of forming
      a left-handed crossover connection between beta-strands S2 and S3. This
      connection is critical to propagate the folding reaction. In the presence of the
      prodomain, folding proceeds through one major intermediate, which is stabilized
      by prodomain binding, independent of metal concentration and proline
      isomerization state. The prodomain also catalyzes the late proline isomerizations
      needed to form metal site B. Rate-limiting proline isomerization is common in
      protein folding, but its effect in slowing subtilisin folding is amplified
      because of the instability of the intermediate and an apparent need for
      simultaneous isomerization of multiple prolines in order to create metal site B.
      Thus, the kinetically controlled folding reaction of subtilisin, although
      unusual, is explained by the accrued effects of events found in other proteins.

PMID- 17223685
TI  - Chemical-scale studies on the role of a conserved aspartate in preorganizing the
      agonist binding site of the nicotinic acetylcholine receptor.
AB  - The nicotinic acetylcholine receptor and related Cys-loop receptors are ligand
      gated ion channels that mediate fast synaptic transmission throughout the central
      and peripheral nervous system. A highly conserved aspartate residue (D89) that is
      near the agonist binding site but does not directly contact the ligand plays a
      critical part in receptor function. Here we probe the role of D89 using unnatural
      amino acid mutagenesis coupled with electrophysiology. Homology modeling
      implicates several hydrogen bonds involving D89. We find that no single hydrogen
      bond is essential to proper receptor function. Apparently, the side chain of D89
      establishes a redundant network of hydrogen bonds; these bonds preorganize the
      agonist binding site by positioning a critical tryptophan residue that directly
      contacts the ligand. Earlier studies of the D89N mutant led to the proposal that
      a negative charge at this position is essential for receptor function. However,
      we find that receptors with neutral side chains at position 89 can function well,
      if the side chain is less perturbing than the amide of asparagine (nitro or keto
      groups allow function) or if a compensating backbone mutation is introduced to
      relieve unfavorable electrostatics.

PMID- 17223687
TI  - Hydrogen-deuterium exchange in free and prodomain-complexed subtilisin.
AB  - Residue-specific exchange rates of 223 amide protons in free and prodomain
      complexed subtilisin were determined in order to understand how the prodomain
      binding affects the energetics of subtilisin folding. In free subtilisin, amide
      protons can be categorized according to exchange rate: 74 fast exchangers (rates
      > or = 1 h(-1)); 52 medium exchangers (rates between 1 h(-1) and 1 day(-1)); 31
      slow exchangers (rates between 1 day(-1) and 0.001 day(-1)). The remaining 66
      amide proteins did not exchange detectibly over 9 months (k(obs) < year(-1)) and
      were denoted as core protons. Core residues occur throughout the main structural
      elements of subtilisin. Prodomain binding results in high protection factors (100
      1000) in the central beta-sheet, particularly in the vicinity of beta-strands S5,
      S6, and S7 and the connecting loops between them. These connecting loops provide
      the ligands to the cation at metal site B. Overall, prodomain binding seems to
      facilitate the organization of the entire central beta-sheet and alpha-helix C in
      the left-handed crossover connection between beta-strands two and three. It also
      appears to facilitate the isomerization of multiple prolines late in folding,
      allowing the formation of metal site B. The gain of stability region around site
      B comes at the cost of stability in regions more distal to prodomain binding: the
      C-terminal alpha-helix H and the N-terminal alpha-helices A and B. The
      acceleration of exchange in these regions by prodomain binding reveals an
      antagonism between the folding intermediate and the full native structure. This
      antagonism helps to explain why the prodomain is needed to stabilize the folding
      intermediate as well as why the unfolding of free subtilisin seldom occurs via
      this intermediate.

PMID- 17223689
TI  - Polypeptide motions are dominated by peptide group oscillations resulting from
      dihedral angle correlations between nearest neighbors.
AB  - To identify basic local backbone motions in unfolded chains, simulations are
      performed for a variety of peptide systems using three popular force fields and
      for implicit and explicit solvent models. A dominant "crankshaft-like" motion is
      found that involves only a localized oscillation of the plane of the peptide
      group. This motion results in a strong anticorrelated motion of the phi angle of
      the ith residue (phi(i)) and the psi angle of the residue i - 1 (psi(i-1)) on the
      0.1 ps time scale. Only a slight correlation is found between the motions of the
      two backbone dihedral angles of the same residue. Aside from the special cases of
      glycine and proline, no correlations are found between backbone dihedral angles
      that are separated by more than one torsion angle. These short time, correlated
      motions are found both in equilibrium fluctuations and during the transit process
      between Ramachandran basins, e.g., from the beta to the alpha region. A residue's
      complete transit from one Ramachandran basin to another, however, occurs in a
      manner independent of its neighbors' conformational transitions. These properties
      appear to be intrinsic because they are robust across different force fields,
      solvent models, nonbonded interaction routines, and most amino acids.

PMID- 17223688
TI  - Inhibition and structure of Trichomonas vaginalis purine nucleoside phosphorylase
      with picomolar transition state analogues.
AB  - Trichomonas vaginalis is a parasitic protozoan purine auxotroph possessing a
      unique purine salvage pathway consisting of a bacterial type purine nucleoside
      phosphorylase (PNP) and a purine nucleoside kinase. Thus, T. vaginalis PNP
      (TvPNP) functions in the reverse direction relative to the PNPs in other
      organisms. Immucillin-A (ImmA) and DADMe-Immucillin-A (DADMe-ImmA) are transition
      state mimics of adenosine with geometric and electrostatic features that resemble
      early and late transition states of adenosine at the transition state stabilized
      by TvPNP. ImmA demonstrates slow-onset tight-binding inhibition with TvPNP, to
      give an equilibrium dissociation constant of 87 pM, an inhibitor release half
      time of 17.2 min, and a Km/Kd ratio of 70,100. DADMe-ImmA resembles a late
      ribooxacarbenium ion transition state for TvPNP to give a dissociation constant
      of 30 pM, an inhibitor release half-time of 64 min, and a Km/Kd ratio of 203,300.
      The tight binding of DADMe-ImmA supports a late SN1 transition state. Despite
      their tight binding to TvPNP, ImmA and DADMe-ImmA are weak inhibitors of human
      and P. falciparum PNPs. The crystal structures of the TvPNP x ImmA x PO4 and
      TvPNP x DADMe-ImmA x PO4 ternary complexes differ from previous structures with
      substrate analogues. The tight binding with DADMe-ImmA is in part due to a 2.7 A
      ionic interaction between a PO4 oxygen and the N1' cation of the
      hydroxypyrrolidine and is weaker in the TvPNP x ImmA x PO4 structure at 3.5 A.
      However, the TvPNP x ImmA x PO4 structure includes hydrogen bonds between the 2'
      hydroxyl and the protein that are not present in TvPNP x DADMe-ImmA x PO4. These
      structures explain why DADMe-ImmA binds tighter than ImmA. Immucillin-H is a 12
      nM inhibitor of TvPNP but a 56 pM inhibitor of human PNP. And this difference is
      explained by isotope-edited difference infrared spectroscopy with [6-18O]ImmH to
      establish that O6 is the keto tautomer in TvPNP x ImmH x PO4, causing an
      unfavorable leaving-group interaction.

PMID- 17223690
TI  - The androgen receptor T877A mutant recruits LXXLL and FXXLF peptides differently
      than wild-type androgen receptor in a time-resolved fluorescence resonance energy
      transfer assay.
AB  - The interactions of the ligand binding domain (LBD) of androgen receptor (AR) and
      the AR T877A mutant, found in prostate cancer, with peptides from coactivator and
      corepressor proteins or random phage display peptides were investigated using in
      vitro time-resolved fluorescence resonance energy transfer (TR-FRET). Interaction
      of wild-type AR LBD with the random phage display peptide D11FxxLF was observed
      with dihydrotestosterone (DHT), testosterone, R1881, estradiol, spironolactone,
      progesterone, and cortisol resulting in distinct dose dependency (EC50) values
      for each ligand and correlating well with the reported rank order potency of
      these agonists. Increasing concentrations of cyproterone acetate and mifepristone
      resulted in more complete disruption of the DHT-mediated AR-D11FxxLF peptide
      interaction, while flutamide, hydroxyflutamide, and bicalutamide caused only
      partial disruption of the complex. The mutant AR T877A LBD exhibited increased
      binding affinities for all ligands tested except for bicalutamide, mifepristone,
      DHT, and R1881 in a competitive binding assay as compared to wild-type AR LBD.
      This mutation was also characterized by increased ligand potency for agonist
      induced peptide recruitment. Although usually an antagonist, hydroxyflutamide was
      more potent in the recruitment of D11FxxLF or an SRC3-1 LXXLL motif to AR T877A
      LBD than AR LBD. The antagonist cyproterone acetate behaved as a full antagonist
      of D11FxxLF recruitment to AR LBD and AR T877A LBD but as a more potent agonist
      in the recruitment of SRC3-1 to AR T877A LBD. These results suggest that the AR
      T877A mutation affects both ligand affinity and ligand dose dependency for
      peptide recruitment and may explain in part the altered responses of antagonists
      and increased transcriptional activation reported in androgen-independent
      prostate cancers.

PMID- 17223692
TI  - Reversible oxidation of the membrane distal domain of receptor PTPalpha is
      mediated by a cyclic sulfenamide.
AB  - Protein tyrosine phosphatases (PTPs) are fundamental to the regulation of
      cellular signalling cascades triggered by protein tyrosine kinases. Most receptor
      like PTPs (RPTPs) comprise two tandem PTP domains, with only the membrane
      proximal domains (D1) having significant phosphatase activity; the membrane
      distal domains (D2) display little to no catalytic activity. Intriguingly,
      however, many RPTP D2s share the catalytically essential Cys and Arg residues of
      D1s. D2 of RPTPalpha may function as a redox sensor that mediates regulation of
      D1 via reactive oxygen species. Oxidation of Cys723 of RPTPalpha D2 (equivalent
      to PTP catalytic Cys residues) stabilizes RPTPalpha dimers, induces rotational
      coupling, and is required for inactivation of D1 phosphatase activity. Here, we
      investigated the structural consequences of RPTPalpha D2 oxidation. Exposure of
      RPTPalpha D2 to oxidants promotes formation of a cyclic sulfenamide species, a
      reversibly oxidized state of Cys723, accompanied by conformational changes of the
      D2 catalytic site. The cyclic sulfenamide is highly resistant to terminal
      oxidation to sulfinic and sulfonic acids. Conformational changes associated with
      RPTPalpha D2 oxidation have implications for RPTPalpha quaternary structure and
      allosteric regulation of D1 phosphatase activity.

PMID- 17223691
TI  - Structural and functional characterization of the aryl hydrocarbon receptor
      ligand binding domain by homology modeling and mutational analysis.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor
      that is activated by a structurally diverse array of synthetic and natural
      chemicals, including toxic halogenated aromatic hydrocarbons such as 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). Analysis of the molecular events occurring in
      the AhR ligand binding and activation processes requires structural information
      on the AhR Per-Arnt-Sim (PAS) B-containing ligand binding domain, for which no
      experimentally determined structure has been reported. With the availability of
      extensive structural information on homologous PAS-containing proteins, a
      reliable model of the mouse AhR PAS B domain was developed by comparative
      modeling techniques. The PAS domain structures of the functionally related
      hypoxia-inducible factor 2alpha (HIF-2alpha) and AhR nuclear translocator (ARNT)
      proteins, which exhibit the highest degree of sequence identity and similarity
      with AhR, were chosen to develop a two-template model. To confirm the features of
      the modeled domain, the effects of point mutations in selected residue positions
      on both TCDD binding to the AhR and TCDD-dependent transformation and DNA binding
      were analyzed. Mutagenesis and functional analysis results are consistent with
      the proposed model and confirm that the cavity modeled in the interior of the
      domain is indeed involved in ligand binding. Moreover, the physicochemical
      characteristics of some residues and of their mutants, along with the effects of
      mutagenesis on TCDD and DNA binding, also suggest some key features that are
      required for ligand binding and activation of mAhR at a molecular level, thus
      providing a framework for further studies.

PMID- 17223693
TI  - Topography studies on the membrane interaction mechanism of the eosinophil
      cationic protein.
AB  - The eosinophil cationic protein (ECP) is an antipathogen protein involved in the
      host defense system. ECP displays bactericidal and membrane lytic capacities
      [Carreras et al. (2003) Biochemistry 42, 6636-6644]. We have now characterized in
      detail the protein-membrane interaction process. All observed fluorescent
      parameters of the wild type and single-tryptophan-containing mutants, as well as
      the results of decomposition analysis of protein fluorescence, suggest that W10
      and W35 belong to two distinct spectral classes I and III, respectively.
      Tryptophan residues were classified and assigned to distinct structural classes
      using statistical approaches based on the analysis of tryptophan microenvironment
      structural properties. W10 belongs to class I and is buried in a relative
      nonpolar, nonflexible protein environment, while W35 (class III) is fully exposed
      to free water molecules. Tryptophan solvent exposure and the depth of the protein
      insertion in the lipid bilayer were monitored by the degree of protein
      fluorescence quenching by KI and brominated phospholipids, respectively. Results
      indicate that W35 partially inserts into the lipid bilayer, whereas W10 does not.
      Further analysis by electron microscopy and dynamic light scattering indicates
      that ECP can destabilize and trigger lipid vesicle aggregation at a nanomolar
      concentration range, corresponding to about 1:1000 protein/lipid ratio. No
      significant leakage of the vesicle aqueous content takes place below that protein
      concentration threshold. The data are consistent with a membrane destabilization
      "carpet-like" mechanism.

PMID- 17223694
TI  - Heat-induced dimerization of BCL-xL through alpha-helix swapping.
AB  - The dimerization of anti-apoptotic BCL-xL by three-dimensional domain swapping
      has recently been discovered at alkaline pH; however, the high energetic barrier
      between the dimer and monomer forms of BCL-xL prevents them from interconverting
      at room temperature and neutral pH. Here, we demonstrate that BCL-xL dimers can
      be easily prepared by heating concentrated protein above 50 degrees C. The 38 kDa
      BCL-xL dimer was fully characterized by multi-resonance nuclear magnetic
      resonance (NMR) spectroscopy, and the mechanism of dimerization by alpha-helix
      swapping was confirmed. Dimerization strongly affects the NMR signals from the
      turn between helices alpha5 and alpha6 of BCL-xL and a portion of the long loop
      between helices alpha1 and alpha2. Measurements of residual dipolar couplings
      demonstrate that the solution structure of the BCL-xL dimer is very close to the
      crystal structure. Dimer formation does not prevent tight binding of ligands to
      the hydrophobic cleft of BCL-xL; however, binding of a BID BH3-peptide or a
      polyphenol drug, gossypol, to BCL-xL significantly slowed monomer-dimer
      interconversion and is an example of the control of BCL protein oligomerization
      by ligand binding.

PMID- 17223695
TI  - Structure-guided peptidomimetic design leads to nanomolar beta-hairpin inhibitors
      of the Tat-TAR interaction of bovine immunodeficiency virus.
AB  - The Tat protein of immunodeficiency viruses is the main activator of viral gene
      expression. By binding specifically to its cognate site, the transactivator
      response element (TAR), Tat mediates a strong induction of the production of all
      viral transcripts. In seeking a new chemical solution to inhibiting viral protein
      RNA interactions, we recently identified inhibitors of the viral Tat protein from
      the bovine immunodeficiency virus (BIV) using conformationally constrained beta
      hairpin peptidomimetics. We identified a micromolar ligand, called BIV2, and the
      structure of its complex with BIV TAR was determined by NMR. In this work, we
      demonstrate that this chemistry can rapidly yield highly potent and selective
      ligands. On the basis of the structure, we synthesized and assayed libraries of
      mutant peptidomimetics. Remarkably, we were able in just a few rounds of design
      and synthesis to discover nanomolar inhibitors of the Tat-TAR interaction in BIV
      that selectively bind the BIV TAR RNA compared to RNA structures as closely
      related as the HIV-1 TAR or RRE elements. The molecular recognition principles
      developed in this study have been exploited in discovering related peptidomimetic
      inhibitors of the Tat-TAR interaction in HIV-1.

PMID- 17223696
TI  - PF0610, a novel winged helix-turn-helix variant possessing a rubredoxin-like Zn
      ribbon motif from the hyperthermophilic archaeon, Pyrococcus furiosus.
AB  - PF0610, a protein from the hyperthermophile Pyrococcus furiosus, has homologues
      only in other archaeal species and in three species of Fe(III)-reducing bacteria.
      It is thought to have a helix-turn-helix (HTH) domain at the N-terminus and
      possesses two CXXC motifs characteristic of metal binding proteins. We have
      determined the solution structure of the Zn-bound protein using NMR. PF0610 is a
      novel winged helix-turn-helix (wHTH) protein with a rubredoxin-like Zn ribbon as
      its W1 segment. In addition, it possesses a large number of basic residues on its
      surface. Clusters of basic residues can be found on both helix H3 and the metal
      binding loops of W1, suggesting that it might be a DNA-binding protein.
      Accordingly, gel shift assays using both linear and circular DNA showed that
      PF0610 does bind DNA, at least in a sequence-independent fashion. Modeling the
      PF0610-DNA interaction based on other wHTH protein-DNA structures revealed that
      besides helix H3, basic residues around the second CXXC motif in the metal
      binding loop could make extensive contacts with DNA. However, the bulkiness of
      the W1 region implies that the DNA conformation may be distorted upon PF0610
      binding. PF0610 is the first protein known to have a Zn ribbon-embedded wHTH fold
      and, as such, has potential roles both as a metal-dependent transcription
      regulator and as a component of the chromosome packing system in P. furiosus. The
      discovery of this novel structure represents the addition of another branch to
      the winged HTH protein family and could contribute to our understanding of
      transcription regulatory processes in P. furiosus.

PMID- 17223697
TI  - Molecular understanding of Abeta peptide interaction with isoflurane, propofol,
      and thiopental: NMR spectroscopic study.
AB  - Abeta peptide is the major component of senile plaques (SP), which accumulate in
      the brain of a patient with Alzheimer's disease (AD). A recent report indicated
      that isoflurane enhanced Abeta oligomerization (micro-aggregation) and subsequent
      cytotoxicity of the Abeta peptide. A separate study showed that a clinically
      relevant concentration of isoflurane induces apoptosis and increases Abeta
      production in a human neuroglioma cell line. In vitro studies have indicated that
      halothane interacts specifically with Abeta peptide to induce oligomerization and
      that Abeta42 oligomerizes faster than Abeta40. The specific interactions of
      isoflurane, propofol, and thiopental with uniformly 15N labeled Abeta40 and
      Abeta42 peptide were investigated using multidimensional nuclear magnetic
      resonance (NMR) experiments. We found that isoflurane and propofol (at higher
      concentration) interact with Abeta40 peptides and induce Abeta oligomerization.
      Thiopental does not interact with specific residues (G29, A30, and I31) of
      Abeta40; hence, the peptide remains in the monomeric form. On the basis of our
      NMR study, thiopental does not oligomerize Abeta40 even at higher concentrations.

PMID- 17223698
TI  - The hinge region between two ubiquitin-like domains destabilizes recombinant
      ISG15 in solution.
AB  - Interferon-stimulated gene (ISG) 15 mediates antiviral responses and also is
      upregulated within the endometrium in response to the developing embryo during
      early pregnancy. Structurally, ISG15 resembles two ubiquitin domains (30%
      identical) that are separated by a hinge region. Recombinant (r) bovISG15 is not
      stable in solution. It was hypothesized that the hinge region contributed to the
      instability of rbovISG15. Within 24 h of dialysis, rbovISG15 formed complexes as
      detected by reducing and denaturing SDS-PAGE. However, chemical perturbations of
      cysteine prevented formation of rbovISG15 complexes over time. Furthermore, a
      site-directed mutant of rbovISG15 (Cys80Ser) was isomeric and more stable than
      rbovISG15. Neither wild-type nor mutant rbovISG15 was able to interact with the
      ISG15 E1 initiating enzyme, UBE1L, in an in vitro pull-down assay. Ovine (ov)
      ISG15 has three additional amino acids within the hinge region that were
      hypothesized to increase stability and the degree of interaction with UBE1L
      because of increased separation of the ubiquitin-like domains. Over time in
      solution, rovISG15 the level of rovISG15 secondary structure was diminished,
      whereas the Cys80Ser rovISG15 structure did not change. A GST-Cys80Ser rovISG15
      fusion protein had increased structural stability and enhanced protein-protein
      interaction with UBE1L after dialysis for 48 h, when compared to the GST-rovISG15
      fusion protein or rbovISG15. Models of bovISG15, Cys80Ser bovISG15, and ovISG15
      were constructed, which confirmed that the hinge region between the two ubiquitin
      domains destabilizes rbovISG15 in solution.

PMID- 17223699
TI  - A structural factor responsible for substrate recognition by Bacillus sp. GL1
      xanthan lyase that acts specifically on pyruvated side chains of xanthan.
AB  - Xanthan is a bacterial heteropolysaccharide composed of pentasaccharide repeating
      units, i.e., a cellobiose as a backbone and a trisaccharide consisting of two
      mannoses and one glucuronic acid as a side chain. Nonreducing terminal mannose
      residues of xanthan side chains are partially pyruvated. Bacillus sp. GL1 xanthan
      lyase, a member of polysaccharide lyase family 8, acts specifically on pyruvated
      side chains of xanthan and yields pyruvated mannose through a beta-elimination
      reaction by using a single Tyr255 residue as base and acid catalysts. Here we
      show structural factors for substrate recognition by xanthan lyase through X-ray
      crystallographic and mutational analyses. The enzyme accommodates mannose and
      pyruvated mannose at the -1 subsite, although both inhibitor and dissociation
      constants of the two monosaccharides indicated that the affinity of pyruvated
      mannose for xanthan lyase is much higher than that of mannose. The high affinity
      of pyruvated mannose is probably due to the formation of additional hydrogen
      bonds between the carboxyl group of pyruvated mannose and amino acid residues of
      Tyr315 and Arg612. Site-directed mutagenesis of the two residues demonstrated
      that Arg612 is a key residue in recognizing pyruvated mannose. Arg612 is located
      in the protruding loop covering the substrate, suggesting that the loop functions
      as a lid that is responsible for the proper accommodation of the substrate at the
      active site.

PMID- 17223700
TI  - Kinetic and structural analysis of enzyme sliding on a substrate: multiple attack
      in beta-amylase.
AB  - Beta-amylase (EC 3.2.1.2) is starch-hydrolyzing exo-type enzyme that can catalyze
      the successive liberation of beta-maltose from the nonreducing ends of alpha-1,4
      linked glucopyranosyl polymers. There is a well-known phenomenon called multiple
      or repetitive attack where the enzyme releases several maltose molecules in a
      single enzyme-substrate complex. In order to understand it further, we examined
      the beta-amylase-catalyzed reaction using maltooligosaccharides. The Monte Carlo
      method was applied for simulation of the beta-amylase-catalyzed reaction
      including the multiple attack mechanism. Through site-directed mutagenesis, we
      have successfully prepared a mutant enzyme which may be simulated as a multiple
      attack action reduced one with retaining significant hydrolytic activity. From
      the results of X-ray structure analysis of the mutant enzyme, it was clarified
      that one carboxyl residue plays a very important role in the multiple attack. The
      multiple attack action needs the force of enzyme sliding on the substrate. In
      addition, it is important for the multiple attack that the enzyme and substrate
      have the characteristics of a stable productive substrate-enzyme complex through
      a hydrogen bond between the nonreducing end of the substrate and the carboxyl
      residue of the enzyme.

PMID- 17223701
TI  - Assignment of red antenna states in photosystem I from Thermosynechococcus
      elongatus by single-molecule spectroscopy.
AB  - Single-molecule spectroscopy at cryogenic temperatures was used to elucidate
      spectral properties, heterogeneities, and dynamics of the chlorophyll a (Chla)
      molecules responsible for the fluorescence in photosystem I (PSI) from the
      cyanobacteria Thermosynechococcus elongatus. Absorption and hole burning data
      suggest the presence of three pools absorbing at wavelengths greater than 700 nm
      with their absorption maxima at 708, 715, and 719 nm. The responsible Chla
      molecules are termed C708, C715, and C719. In the emission spectra of single PSI
      complexes, zero-phonon lines (ZPLs) were observed over the whole red emission
      range of PSI. The spectral region of the C708 pool is dominated by intense ZPLs;
      on the other hand, the broad emission of C715/C719 is unstructured and ZPLs are
      seen in this region much less frequently. Spectral jumps of ZPLs were observed.
      The dynamics as well as the spectral range covered by such jumps differ for C708
      and C715/C719. This heterogeneity is likely caused by differences in the close
      environment of the chromophores. A tentative assignment of C708 and C715/C719 to
      Chla dimers and a Chla trimer is discussed, which is based on the remarkable
      structural differences in the environment of the most probable candidates for the
      red-most fluorescence.

PMID- 17223702
TI  - Kinetic and structural studies of specific protein-protein interactions in
      substrate catalysis by Cdc25B phosphatase.
AB  - Using a combination of steady-state and single-turnover kinetics, we probe
      substrate association, dissociation, and chemistry for the reaction of Cdc25B
      phosphatase with its Cdk2-pTpY/CycA protein substrate. The rate constant for
      substrate association for the wild-type enzyme is 1.3 x 10(6) M(-1) s(-1). The
      rate constant for dissociation is slow compared to the rate constant for
      phosphate transfer to form the phospho-enzyme intermediate (k2 = 1.1 s(-1)),
      making Cdk2-pTpY/CycA a sticky substrate. Compared to the wild type, all hotspot
      mutants of residues at the remote docking site that specifically affect catalysis
      with the protein substrate (Arg488, Arg492, and Tyr497 on Cdc25B and Asp206 on
      Cdk2) have greatly slowed rate constants of association (70- to 4500-fold), and
      some mutants have decreased k2 values compared to that of the wild type. Most
      dramatically, R492L, despite showing no significant changes in a crystal
      structure at 2.0 A resolution, has an approximately 100-fold decrease in k2
      compared to that of wild-type Cdc25B. The active site C473S mutant binds tightly
      to and dissociates slowly from Cdk2-pTpY/CycA (Kd = 10 nM, k(off) = 0.01 s(-1)).
      In contrast, the C473D mutant, despite showing only localized perturbations in
      the active site at 1.6 A resolution, has a much weaker affinity and dissociates
      rapidly (Kd of 2 microM, k(off) > 2 s(-1)) from the protein substrate. Overall,
      we demonstrate that the association of Cdc25B with its Cdk2-pTpY/CycA substrate
      is governed to a significant extent by the interactions of the remote hotspot
      residues, whereas dissociation is governed by interactions at the active site.

PMID- 17223703
TI  - A mobile tryptophan is the intrinsic charge transfer donor in a flavoenzyme
      essential for nikkomycin antibiotic biosynthesis.
AB  - The flavoenzyme nikD is required for the biosynthesis of nikkomycin antibiotics.
      NikD exhibits an unusual long wavelength absorption band attributed to a charge
      transfer complex of FAD with an unknown charge transfer donor. NikD crystals
      contain an endogenous active site ligand. At least four different compounds are
      detected in nikD extracts, including variable amounts of two ADP derivatives that
      bind to the enzyme's dinucleotide binding motif in competition with FAD,
      picolinate (0.07 mol/mol of nikD) and an unknown picolinate-like compound.
      Picolinate, the product of the physiological catalytic reaction, matches the
      properties deduced for the active site ligand in nikD crystals. The charge
      transfer band is eliminated upon mixing nikD with excess picolinate but not by a
      reversible unfolding procedure that removes the picolinate-like compound, ruling
      out both compounds as the intrinsic charge transfer donor. Mutation of Trp355 to
      Phe eliminates the charge transfer band, accompanied by a 30-fold decrease in
      substrate binding affinity. The results provide definitive evidence for Trp355 as
      the intrinsic charge transfer donor. The indole ring of Trp355 is coplanar with
      or perpendicular to the flavin ring in "open" or "closed" crystalline forms of
      nikD, respectively. Importantly, a coplanar configuration is required for charge
      transfer interaction. Absorption in the long wavelength region therefore
      constitutes a valuable probe for monitoring conformational changes in solution
      that are likely to be important in nikD catalysis.

PMID- 17223704
TI  - 3'-Azido-3'-deoxythymidine-(5')-tetraphospho-(5')-adenosine, the product of ATP
      mediated excision of chain-terminating AZTMP, is a potent chain-terminating
      substrate for HIV-1 reverse transcriptase.
AB  - The resistance of HIV-1 to 3'-azido-3'-deoxythymidine (AZT) involves
      phosphorolytic excision of chain-terminating AZT-5'-monophosphate (AZTMP). Both
      pyrophosphate (PPi) and ATP act as excision substrates in vitro, but the
      intracellular substrate used during replication of AZT-resistant HIV is still
      unknown. PPi-mediated excision produces AZT-5'-triphosphate (AZTTP), which could
      be immediately re-used as a substrate for viral DNA chain termination. In
      contrast, ATP-mediated excision produces the novel compound AZT-(5')-tetraphospho
      (5')-adenosine (AZTp4A). Since little is known of the interaction of AZTp4A with
      HIV-1 RT, we carried out kinetic and molecular modeling studies to probe this.
      AZTp4A was found to be a potent inhibitor of HIV-1 RT-catalyzed DNA synthesis and
      of both ATP- and PPi-mediated AZTMP excision. AZTp4A is in fact an excellent
      chain-terminating substrate for AZT-resistant RT-catalyzed DNA synthesis, better
      than AZTTP (k(pol)/Kd = 6.2 and 11.9 for AZTTP and AZTp4A, respectively). The
      affinity of AZT-resistant HIV-1 RT for AZTp4A is at least 30,000-fold greater
      than that for the excision substrate ATP and approximately 10-fold greater than
      that for AZTTP. Dissociation of newly formed AZTp4A from RT may therefore provide
      a significant rate-limiting step for continued HIV-1 DNA synthesis. Our studies
      show that the products of PPi- and ATP-mediated excision of chain-terminating
      AZTMP (AZTTP and AZTp4A, respectively) are both potent chain-terminating
      substrates for HIV-1 RT, suggesting that there is no obvious benefit to HIV using
      ATP instead of PPi as the excision substrate.

PMID- 17223705
TI  - Temperature-dependent structure of the E x S complex of Bacillus
      stearothermophilus alcohol dehydrogenase.
AB  - The catalytic chemistry of the thermophilic Bacillus stearothermophilus alcohol
      dehydrogenase (HtADH) closely resembles that of mesophilic horse liver alcohol
      dehydrogenase (HLADH). Molecular dynamics (MD) simulations of the htADH x NAD+ x
      EtO- complex at 298, 323, and 348 K show that the structure of the ligated
      Zn2+...EtO- complex varies slightly with change in temperature. The MD-created
      Boltzmann distribution of htADH x NAD+ x EtO- structures establishes the
      formation of multiple states which increase in number with a decrease in
      temperature. The motions of the cofactor domain are highly correlated with the
      motions of NAD+ at the optimal growth temperature (348 K), with NAD+ being pushed
      toward the substrate by Val260. With a decrease in temperature, the motion
      together of the cofactor and substrate is reversed, and at 298 K, the
      nicotinamide ring of the cofactor moves away from the substrate. Both the
      distance between and the angle of approach of C4 of NAD+ and HD of EtO- become
      distorted from those of the reactive conformation. The percentages of ground
      state present as the reactive conformation at different temperatures are
      approximately correlated with the kcat for the htADH enzymatic reaction. The rate
      constant for the htADH x NAD+ x EtOH --> htADH x NAD+ x EtO- proton dissociation,
      which is mediated by Thr40-OH, becomes slower at lower temperatures. The time
      dependent distance between EtO- and Thr40-OH reveals that the Thr40 hydroxyl
      group sways between the substrate and NAD+ ribose 2'-hydroxyl group at the
      optimal enzyme growth temperature, and this movement is effectively frozen out as
      the temperature decreases. The temperature dependence of active site
      conformations is due to the change in both long-range and short-range motions of
      the E x S complex.

PMID- 17223706
TI  - Identification and characterization of a biomineralization related gene PFMG1
      highly expressed in the mantle of Pinctada fucata.
AB  - To elucidate the mechanism of nacre biomineralization, the mantle of Pinctada
      fucata (P. fucata) from the South China Sea was used. Using the mantle cDNA
      library and the ESTs we have cloned through suppression subtractive hybridization
      (SSH), ten novel genes including PFMG1 were obtained through nested PCR.
      Bioinformative results showed that PFMG1 had a high homology (40%) with
      Onchocerca volvulus calcium-binding protein CBP-1 and had two EF-hand calcium
      binding domains from the 81st to the 93rd amino acid and from the 98th to the
      133rd amino acid in the deduced amino acid sequence. The results of multitissue
      RT-PCR and in situ hybridization demonstrated the high expression of PFMG1 in the
      mantle of P. fucata and confirmed the SSH method. The results of GST-PFMG1 on
      CaCO3 crystallization showed significant effects on nucleation and precipitation
      of CaCO3. PFMG1 was cloned into the pcDNA.3.1/myc-HisA vector and was
      subsequently transfected into MC3T3-E1 cells. RT-PCR revealed upregulation of the
      marker genes related to cell growth, differentiation, and mineralization, and BMP
      2, osterix, and osteopontin were upregulated as a result. This research work
      suggests that PFMG1 plays an important role in the nacre biomineralization, and
      the SSH method can pave the way for the bulk cloning and characterization of new
      genes involved in biomineralization in P. fucata and may accelerate research on
      the mechanism of pearl formation.

PMID- 17223707
TI  - Nonpolar substitution at the C-terminus of the prion protein, a mimic of the
      glycosylphosphatidylinositol anchor, partially impairs amyloid fibril formation.
AB  - In contrast to most amyloidogenic proteins or peptides that do not contain any
      significant posttranslational modifications, the prion protein (PrP) is modified
      with either one or two polysaccharides and a GPI anchor which attaches PrP to the
      plasma membrane. Like other amyloidogenic proteins, however, PrP adopts a
      fibrillar shape when converted to a disease-specific conformation. Therefore, PrP
      polymerization offers a unique opportunity to examine the effects of biologically
      relevant nonpeptidic modifications on conversion to the amyloid conformation. To
      test the extent to which a long hydrophobic chain at the C-terminus affects the
      intrinsic amyloidogenic propensity of PrP, we modified recombinant PrP with an N
      myristoylamidomaleimidyl group, which can serve as a membrane anchor. We show
      that while this modification increases the affinity of PrP for the cell membrane,
      it does not alter the structure of the protein. Myristoylation of PrP affected
      amyloid formation in two ways: (i) it substantially decreased the extent of
      fibrillation, presumably due to off-pathway aggregation, and (ii) it prohibited
      assembly of filaments into higher order fibrils by preventing their lateral
      association. The negative effect on lateral association was abolished if the
      myristoylated moiety at the C-terminus was replaced by a polar group of similar
      size or by a hydrophobic group of smaller size. When preformed PrP fibrils were
      provided as seeds, myristoylated PrP supported fibril elongation and formation of
      higher order fibrils composed of several filaments. Our studies illustrate that,
      despite a bulky hydrophobic moiety at C-terminus, myristoylated PrP can still
      incorporate into fibrillar structure and that the C-terminal hydrophobic
      substitution does not affect the size of the proteinase K resistant core but
      controls the mode of lateral assembly of filaments into higher order fibrils.

PMID- 17223708
TI  - Thermodynamic characterization of the interaction between CAR-RXR and SRC-1
      peptide by isothermal titration calorimetry.
AB  - The constitutive androstane receptor (CAR) enhances transcription of specific
      target genes that regulate several metabolic pathways. CAR functions as an
      obligate heterodimer (CAR-RXR) with the retinoid X receptor (RXR). Also part of
      the active receptor complex is the steroid receptor coactivator-1 (SRC-1) which
      interacts with the receptor complex via specific receptor interaction domains
      (RIDs). A peptide derived from SRC-1 RID2 is used to study the thermodynamic
      properties of the interaction with the CAR-RXR ligand binding domain (LBD)
      complex. In the absence of ligands for both CAR and RXR, binding of coactivator
      peptide to the CAR-RXR heterodimer is characterized by a favorable enthalpy
      change and an unfavorable entropy change. The addition of the CAR agonist,
      TCPOBOP, increases the affinity for coactivator by decreasing the unfavorable
      entropy and increasing the favorable intrinsic enthalpy of the interaction. The
      RXR ligand, 9-cis-RA, generates a second SRC-1 site and increases the affinity by
      improving the entropic component of binding. There is an additional increase in
      affinity for one of the two sites in the presence of both ligands. The change in
      heat capacity (deltaCp) is also investigated. A 2-fold difference in deltaCp is
      observed between liganded and unliganded CAR-RXR. The observed thermodynamic
      parameters for binding of SRC-1 peptide to liganded and apo CAR-RXR as well as
      the difference in the deltaCp data provide evidence that the apo CAR-RXR
      heterodimer is conformationally mobile. The more favorable enthalpic contribution
      for TCPOBOP-bound CAR-RXR indicates that preformation of the binding site
      improves the complementarity of the coactivator-receptor interaction.

PMID- 17223709
TI  - A proposed proton shuttle mechanism for saccharopine dehydrogenase from
      Saccharomyces cerevisiae.
AB  - Saccharopine dehydrogenase [N6-(glutaryl-2)-L-lysine:NAD oxidoreductase (L-lysine
      forming)] catalyzes the final step in the alpha-aminoadipate pathway for lysine
      biosynthesis. It catalyzes the reversible pyridine nucleotide-dependent oxidative
      deamination of saccharopine to generate alpha-Kg and lysine using NAD+ as an
      oxidizing agent. The proton shuttle chemical mechanism is proposed on the basis
      of the pH dependence of kinetic parameters, dissociation constants for
      competitive inhibitors, and isotope effects. In the direction of lysine
      formation, once NAD+ and saccharopine bind, a group with a pKa of 6.2 accepts a
      proton from the secondary amine of saccharopine as it is oxidized. This
      protonated general base then does not participate in the reaction again until
      lysine is formed at the completion of the reaction. A general base with a pKa of
      7.2 accepts a proton from H2O as it attacks the Schiff base carbon of
      saccharopine to form the carbinolamine intermediate. The same residue then serves
      as a general acid and donates a proton to the carbinolamine nitrogen to give the
      protonated carbinolamine. Collapse of the carbinolamine is then facilitated by
      the same group accepting a proton from the carbinolamine hydroxyl to generate
      alpha-Kg and lysine. The amine nitrogen is then protonated by the group that
      originally accepted a proton from the secondary amine of saccharopine, and
      products are released. In the reverse reaction direction, finite primary
      deuterium kinetic isotope effects were observed for all parameters with the
      exception of V2/K(NADH), consistent with a steady-state random mechanism and
      indicative of a contribution from hydride transfer to rate limitation. The pH
      dependence, as determined from the primary isotope effect on DV2 and
      D(V2/K(Lys)), suggests that a step other than hydride transfer becomes rate
      limiting as the pH is increased. This step is likely protonation/deprotonation of
      the carbinolamine nitrogen formed as an intermediate in imine hydrolysis. The
      observed solvent isotope effect indicates that proton transfer also contributes
      to rate limitation. A concerted proton and hydride transfer is suggested by
      multiple substrate/solvent isotope effects, as well as a proton transfer in
      another step, likely hydrolysis of the carbinolamine. In agreement, dome-shaped
      proton inventories are observed for V2 and V2/K(Lys), suggesting that proton
      transfer exists in at least two sequential transition states.

PMID- 17223710
TI  - Evidence for coupled motion and hydrogen tunneling of the reaction catalyzed by
      glutamate mutase.
AB  - Glutamate mutase is one of a group of adenosylcobalamin-dependent enzymes that
      catalyze unusual isomerizations that proceed through organic radical
      intermediates generated by homolytic fission of the coenzyme's unique cobalt
      carbon bond. These enzymes are part of a larger family of enzymes that catalyze
      radical chemistry in which a key step is the abstraction of a hydrogen atom from
      an otherwise inert substrate. To gain insight into the mechanism of hydrogen
      transfer, we previously used pre-steady-state, rapid-quench techniques to measure
      the alpha-secondary tritium kinetic and equilibrium isotope effects associated
      with the formation of 5'-deoxyadenosine when glutamate mutase was reacted with
      [5'-(3)H]adenosylcobalamin and L-glutamate. We showed that both the kinetic and
      equilibrium isotope effects are large and inverse, 0.76 and 0.72, respectively.
      We have now repeated these measurements using glutamate deuterated in the
      position of hydrogen abstraction. The effect of introducing a primary deuterium
      kinetic isotope effect on the hydrogen transfer step is to reduce the magnitude
      of the secondary kinetic isotope effect to a value close to unity, 1.05 +/- 0.08,
      whereas the equilibrium isotope effect is unchanged. The significant reduction in
      the secondary kinetic isotope effect is consistent with motions of the 5'
      hydrogen atoms being coupled in the transition state to the motion of the
      hydrogen undergoing transfer, in a reaction that involves a large degree of
      quantum tunneling.

PMID- 17223711
TI  - Complete kinetic mechanism of homoisocitrate dehydrogenase from Saccharomyces
      cerevisiae.
AB  - The kinetic mechanism of homoisocitrate dehydrogenase from Saccharomyces
      cerevisiae was determined using initial velocity studies in the absence and
      presence of product and dead end inhibitors in both reaction directions. Data
      suggest a steady state random kinetic mechanism. The dissociation constant of the
      Mg-homoisocitrate complex (MgHIc) was estimated to be 11 +/- 2 mM as measured
      using Mg2+ as a shift reagent. Initial velocity data indicate the MgHIc complex
      is the reactant in the direction of oxidative decarboxylation, while in the
      reverse reaction direction, the enzyme likely binds uncomplexed Mg2+ and alpha
      ketoadipate. Curvature is observed in the double-reciprocal plots for product
      inhibition by NADH and the dead-end inhibition by 3-acetylpyridine adenine
      dinucleotide phosphate when MgHIc is the varied substrate. At low concentrations
      of MgHIc, the inhibition by both nucleotides is competitive, but as the MgHIc
      concentration increases, the inhibition changes to uncompetitive, consistent with
      a steady state random mechanism with preferred binding of MgHIc before NAD.
      Release of product is preferred and ordered with respect to CO2, alpha
      ketoadipate, and NADH. Isocitrate is a slow substrate with a rate (V/E(t)) 216
      fold slower than that measured with HIc. In contrast to HIc, the uncomplexed form
      of isocitrate and Mg2+ bind to the enzyme. The kinetic mechanism in the direction
      of oxidative decarboxylation of isocitrate, on the basis of initial velocity
      studies in the absence and presence of dead-end inhibitors, suggests random
      addition of NAD and isocitrate with Mg2+ binding before isocitrate in rapid
      equilibrium, and the mechanism approximates rapid equilibrium random. The Keq for
      the overall reaction measured directly using the change in NADH as a probe is
      0.45 M.

PMID- 17223712
TI  - Rapid activation of c-Src kinase by dioxin is mediated by the Cdc37-HSP90 complex
      as part of Ah receptor signaling in MCF10A cells.
AB  - We investigated the mechanism by which activation of the Ah receptor by dioxin
      (TCDD) was accompanied by rapid activation of c-Src kinase activity. A Western
      blotting analysis showed that such action of TCDD in MCF10A cells could
      effectively be suppressed by treatment with a specific inhibitor of Src family
      kinase, PP-2, as judged by Western blot detection of the active form of Src
      protein, indicating that Src kinase is directly activated by TCDD. Such an event,
      occurring within 10-30 min of the addition of TCDD, is also accompanied by
      simultaneous translocation of both Src and cdc37 proteins from cytosol into the
      100,000 x g membrane fraction containing the plasma membrane. By dissociating the
      cytosolic Src-cdc37-HSP90 complex with 17 nM geldanamycin, an optimum
      concentration for affecting this cytosolic cdc37 complex, but not the cytosolic
      Ah receptor complex, we could show that the action of TCDD in activating c-Src
      and cdc37 was abolished, but not its action on CYP1A1. The important role of
      cdc37 in the action of TCDD-induced activation of c-Src was also confirmed by
      blocking cdc37 gene translation with the antisense oligonucleotide treatment as
      well as the siRNA preparation designed to silence cdc37 expression. To understand
      the functional meaning of the disruption of the Src-cdc37-HSP90 complex by 17 nM
      geldanamycin at the cellular level, we investigated its effect on TCDD-induced
      anti-apoptotic action. The results showed that geldanamycin at this concentration
      could also abolish this cellular effect of TCDD. Interestingly, such a role of
      cdc37 in mediating the action of TCDD appears to be limited to activation of c
      Src kinase, but not kinases associated with activation of NFkB, C/EBPalpha, or
      ERK. Together, these observations support the hypothesis that there is a specific
      coordination between the activation of the cytosolic Ah receptor and the c-Src-
      and cdc37-containing HSP90 complex.

PMID- 17223713
TI  - Role of the C-terminal Gly-Gly motif of Escherichia coli MoaD, a molybdenum
      cofactor biosynthesis protein with a ubiquitin fold.
AB  - In Escherichia coli, the MoaD protein plays a central role in the conversion of
      precursor Z to molybdopterin (MPT) during molybdenum cofactor biosynthesis. MoaD
      has a fold similar to that of ubiquitin and contains a highly conserved C
      terminal Gly-Gly motif, which in its active form contains a transferrable sulfur
      in the form of a thiocarboxylate group. During MPT biosynthesis, MoaD cycles
      between two different heterotetrameric complexes, one with MoaE to form MPT
      synthase and the other with MoeB, a protein similar to E1 in the ubiquitin
      pathway, to regenerate its transferrable sulfur. To determine the specific roles
      of each of the two terminal Gly residues with regard to the MoaD cycle, variants
      at the penultimate (Gly80) or terminal (Gly81) residues of both MoaD and
      thiocarboxylated MoaD were created. These variants were analyzed to determine
      their effects on complex formation with MoaE and MoeB, formation of the MoaD-acyl
      adenylate complex, transfer of sulfur to precursor Z to form MPT, and total
      cofactor biosynthesis. The combined results show that while conservative
      substitutions at Gly80 had little effect on any of the processes that were
      examined, the terminal MoaD residue (Gly81) is important for transfer of sulfur
      to precursor Z and essential for formation of the MoaD-AMP complex. These results
      further our understanding of the mechanistic similarities of the MoaD-MoeB
      reaction to that of the ubiquitin-E1 system.

PMID- 17223714
TI  - Influence of the Hofmeister anions on protein stability as studied by thermal
      denaturation and chemical shift perturbation.
AB  - The influence of external cosolutes on the thermal stability of the B1 domain of
      protein L (ProtL) has been studied by circular dichroism, fluorescence
      spectroscopy, and differential scanning calorimetry. The thermal denaturation
      midpoint is effectively modulated by the addition of a suite of anions and
      follows the Hofmeister series. The maximum increase in thermostability
      (corresponding to 14 degrees C) was observed in the presence of 1 M sodium
      sulfate. After conversion of the experimental data into the change in the virial
      coefficient, a mechanistic model was used to estimate the relative contributions
      from excluded volume and preferential anion solvation for each anion. As
      expected, the excluded volume term stabilizes the native conformation of ProtL
      for all the cosolutes, but opposite effects on protein stability arise from the
      anion's solvation depending on their tendency to interact with or to become
      excluded from the protein surface. This behavior is in agreement with the results
      of independent NMR experiments: the anions that strongly interact with the
      protein surface produce significant perturbations in the amide protein chemical
      shift (delta d23(HN)). A correlation obtained between delta d23(HN) and the
      temperature coefficients for the different amide protons provides qualitative
      information about the structural determinants for the interaction between the
      protein surface and the cosolute.

PMID- 17223715
TI  - Modulation of diacylglycerol kinase theta activity by alpha-thrombin and
      phospholipids.
AB  - Diacylglycerol kinase modulates the levels of diacylglycerol and phosphatidic
      acid, two critical lipid second messengers, yet little is known about the effects
      of cellular stimulation on the kinetic behavior of this enzyme. We examined the
      effects of alpha-thrombin and activating phospholipids on the activity and
      substrate affinity of a soluble diacylglycerol kinase, DGKtheta. Our data
      demonstrate that the apparent binding parameters of DGKtheta increase following
      thrombin stimulation, suggesting that alpha-thrombin antagonizes DGKtheta
      activity. Interestingly, this effect is obscured in the presence of high bulk
      substrate concentrations. Given the known stimulatory effects of
      phosphatidylserine on many diacylglycerol kinases, we examined the effects of
      various phospholipids on DGKtheta and found that phosphatidic acid is a more
      effective activator than phosphatidylserine. Phosphatidic acid decreased the
      apparent surface K(M) (K(M(surf))app) of DGKtheta for dioleoylglycerol (DOG) and
      promoted binding to vesicles in a dose-dependent manner. Phosphatidylserine also
      lowered the K(M(surf))app of DGKtheta, though higher concentrations were required
      to achieve the same effect. Interestingly, PS promoted binding to vesicles only
      when present at levels beyond that required to saturate enzyme activity,
      suggesting that PS and PA activate DGKtheta through different mechanisms. The
      potential physiological implications of these findings are discussed.

PMID- 17223716
TI  - SOS: sock/stocking on sign.

PMID- 17223717
TI  - Long history of itchy red-brown papules.

PMID- 17223718
TI  - Peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) in the elderly can be: 1) asymptomatic, 2)
      associated with intermittent claudication, or 3) cause critical limb ischemia.
      Persons with PAD are at increased risk for all-cause mortality, cardiovascular
      mortality, and mortality from coronary artery disease (CAD). Hypertension,
      diabetes mellitus, dyslipidemia, and hypothyroidism should be treated, and
      smoking should be stopped. Statins reduce the incidence of intermittent
      claudication and increase exercise duration until the onset of intermittent
      claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs
      (eg, aspirin, clopidogrel, angiotensin-converting enzyme [ACE] inhibitors,
      statins) should be given to all persons with PAD. Beta blockers should be given
      if CAD is present. Exercise rehabilitation programs and cilostazol lengthen
      exercise time until leg pain develops. Chelation therapy has no scientific basis
      and should be avoided. Revascularization or amputation may be indicated in some
      cases.

PMID- 17223719
TI  - Meeting the mental health needs of older adults.
AB  - Greater attention to the mental health needs of older adults is critical in light
      of recent research documenting substantial undertreatment of mental health
      problems in late life. As often the first and only point of professional contact
      for mentally ill older adults, primary care physicians have an important and
      unique role in reducing enduring unmet mental health needs in late life. This
      article reviews the current state of geriatric mental health care delivery and
      provides valuable information and resources for use in clinical practice to
      increase and enhance primary care detection, treatment, and referral of
      psychological problems in older patients.

PMID- 17223720
TI  - Retinoic acid attenuates the mild hyperoxic lung injury in newborn mice.
AB  - Neonatal exposure to hyperoxia alters lung development in mice. We tested if
      retinoic acid (RA) treatment is capable to affect lung development after
      hyperoxic injury and to maintain structural integrity of lung. The gene of
      vascular endothelial growth factor A (VEGF-A) is one of the RA-responsive genes.
      Newborn BALB/c mice were exposed to room air, 40% or 80% hyperoxia for 7 days.
      One half of animals in each group received 500 mg/kg retinoic acid from day 3 to
      day 7 of the experiment. At the end of experiment we assessed body weight (BW),
      lung wet weight (LW), the wet-to-dry lung weight ratio (W/D) and the expression
      of mRNA for VEGF-A and G3PDH genes. On day 7 the hyperoxia-exposed sham-treated
      mice (group 80) weighed 20% less than the room air-exposed group, whereas the 80%
      hyperoxic group treated with RA weighed only 13% less than the normoxic group.
      W/D values in 80 and 80A groups did not differ, although they both differed from
      the control group and from 40 groups. There was a significant difference between
      40 and 40A groups, but the control group was different from 40 group but not from
      40A groups. The 80 and 80A groups had mRNA VEGF-A expression lowered to 64% and
      41% of the control group. RA treatment of normoxic and mild hyperoxic groups
      increased mRNA VEGF-A expression by about 50%. We conclude that the retinoic acid
      treatment of newborn BALB/c mice exposed for 7 days to 80% hyperoxia reduced the
      growth retardation in the 80 % hyperoxic group, reduced the W/D ratio in the 40%
      but not in the 80 % hyperoxic group. Higher VEGF-A mRNA expression in the 80%
      hyperoxic group treated with RA was not significant compared to the 80% hyperoxic
      group.

PMID- 17223721
TI  - Actions of angiotensin II and dopamine in the medial preoptic area on prolactin
      secretion.
AB  - Dopamine (DA) is known as a primary regulator of prolactin secretion (PRL) and
      angiotensin II (Ang II) has been recognized as one brain inhibitory factor of
      this secretion. In this work, estrogen-primed or unprimed ovariectomized rats
      were submitted to the microinjection of saline or Ang II after previous
      microinjection of saline or of DA antagonist (haloperidol, sulpiride or SCH) both
      in the medial preoptic area (MPOA). Our study of these interactions has shown
      that 1) estrogen-induced PRL secretion is mediated by Ang II and DA actions in
      the MPOA, i.e. very high plasma PRL would be prevented by inhibitory action of
      Ang II, while very low levels would be prevented in part by stimulatory action of
      DA through D(2) receptors, 2) the inhibitory action of Ang II depends on estrogen
      and is mediated in part by inhibitory action of DA through D(1) receptors and in
      other part by inhibition of stimulatory action of DA through D(2) receptors.

PMID- 17223722
TI  - The effect of C-type natriuretic peptide on delayed rectifier potassium currents
      in gastric antral circular myocytes of the guinea-pig.
AB  - C-type natriuretic peptides (CNP) play an inhibitory role in smooth muscle
      motility of the gastrointestinal tract, but the effect of CNP on delayed
      rectifier potassium currents is still unclear. This study was designed to
      investigate the effect of CNP on delayed rectifier potassium currents and its
      mechanism by using conventional whole-cell patch-clamp technique in guinea-pig
      gastric myocytes isolated by collagenase. CNP significantly inhibited delayed
      rectifier potassium currents [I(K (V))] in dose-dependent manner, and CNP
      inhibited the peak current elicited by depolarized step pulse to 86.1+/-1.6 %
      (n=7, P<0.05), 78.4+/-2.6 % (n=10, P<0.01) and 67.7+/-2.3 % (n=14, P<0.01), at
      concentrations of 0.01 micromol/l, 0.1 micromol/l and 1 micromol/l, respectively,
      at +60 mV. When the cells were preincubated with 0.1 micromol/l LY83583, a
      guanylate cyclase inhibitor, the 1 ?micromol/l CNP-induced inhibition of I(K (V))
      was significantly impaired but when the cells were preincubated with 0.1
      micromol/l zaprinast, a cGMP-sensitive phosphodiesterase inhibitor, the 0.01
      micromol/l CNP-induced inhibition of I(K (V)) was significantly potentiated. 8-Br
      cGMP, a membrane permeable cGMP analogue mimicked inhibitory effect of CNP on I(K
      (V)). CNP-induced inhibition of I(K (V)) was completely blocked by KT5823, an
      inhibitor of cGMP-dependent protein kinase (PKG). The results suggest that CNP
      inhibits the delayed rectifier potassium currents via cGMP-PKG signal pathway in
      the gastric antral circular myocytes of the guinea-pig.

PMID- 17223723
TI  - Involvement of nitric oxide in noradrenaline-induced changes in the activity of
      antioxidant enzymes and lipid peroxidation in rat brown adipose tissue and heart.
AB  - The effect of exogenous noradrenaline (NA) (1.6 mg x kg(-1) i.p., 35 min prior
      sacrifice) on the activity of antioxidant enzymes (AOE) copper zinc superoxide
      dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD) and catalase (CAT),
      as well as lipid peroxides (LP) concentration were studied in the rat
      interscapular brown adipose tissue (IBAT) and heart of saline (controls) and
      N(omega)-nitro-L-arginine methyl ester (L-NAME) treated rats (10 mg x kg(-1),
      i.p., during 3 days and 20 min before NA). NA differently affects both AOE
      activities and LP production in the IBAT and heart. Thus, NA inhibited the
      activity of all IBAT AOE and LP production while in the heart it markedly
      increased CAT activity only, but had no effect on any of SODs activities and LP
      concentration. L-NAME, a nitric oxide synthase blocker, completely abolished the
      NA-induced inhibition of the IBAT AOE and LP production, whereas in the heart it
      was without effect. In conclusion, these results indicate that both NA and L-NAME
      effects on AOE activity and LP production are tissue specific and also suggest
      that nitric oxide mediates the NA-induced inhibition of AOE activity and LP
      production in the IBAT only.

PMID- 17223724
TI  - Ontogeny of reactive nitrogen species production by blood phagocytes in pigs.
AB  - The aim of this work was to evaluate ontogeny of reactive nitrogen species (RNS)
      production by peripheral blood phagocytes in pig. Pig fetuses (55 and 92 days of
      gestation) and postnatal piglets (1, 3, 8, 17, 31 and 41 days after birth) were
      used. RNS production was measured by fluorescent probes diaminofluorescein
      diacetate (DAF-FMDA) and dichloro-fluorescein-diacetate (H2DCFDA). Levels of
      nitration of cell proteins were established by immunofluorescent detection of
      nitrotyrosine. Levels of plasma nitrites/nitrates were detected
      spectrophotometrically by Griess reaction. Nitric oxide production measured by
      DAF-FMDA in neutrophils decreased during postnatal life. Spontaneous RNS measured
      by H2DCFDA decreased from 55th day of gestation to the 41st day of life. Phorbol
      12-myristate-13-acetate activated production decreased during postnatal life.
      Production of NO measured by DAF-FMDA in macrophages decreased from the first to
      41st day after birth. RNS production measured by H2DCFDA in monocytes did not
      show any significant changes during ontogeny. The level of nitrotyrosine
      significantly decreased from the third to 17th day. Levels of plasma
      nitrites/nitrates gradually decreased from the 55th day of gestation to the 41st
      day after birth. A temporary increase in all parameters occurred after weaning,
      but without any significance. In conclusion, RNS production has a decreasing
      trend during ontogeny and is transiently upregulated after weaning.

PMID- 17223725
TI  - Impaired microvascular reactivity and endothelial function in patients with
      Cushing's syndrome: influence of arterial hypertension.
AB  - The aim of the study was to evaluate skin microvascular reactivity (MVR) and
      possible influencing factors (fibrinolysis, oxidative stress, and endothelial
      function) in patients with Cushing's syndrome. Twenty-nine patients with active
      Cushing's syndrome (ten of them also examined after a successful operation) and
      16 control subjects were studied. Skin MVR was measured by laser Doppler
      flowmetry during post-occlusive (PORH) and thermal hyperemia (TH).
      Malondialdehyde and Cu,Zn-superoxide dismutase were used as markers of oxidative
      stress. Fibrinolysis was estimated by tissue plasminogen activator (tPA) and its
      inhibitor (PAI-1). N-acetyl-beta-glucosaminidase, E-selectin, P-selectin, and
      ICAM-1 were used as markers of endothelial function. Oxidative stress and
      endothelial dysfunction was present in patients with hypercortisolism, however,
      increased concentration of ICAM-1 was also found in patients after the operation
      as compared to controls (290.8+/-74.2 vs. 210.9+/-56.3 ng.ml(-1), p<0.05).
      Maximal perfusion was significantly lower in patients with arterial hypertension
      during PORH and TH (36.3+/-13.0 vs. 63.3+/-32.4 PU, p<0.01, and 90.4+/-36.6 vs.
      159.2+/-95.3 PU, p<0.05, respectively) and similarly the velocity of perfusion
      increase during PORH and TH was lower (3.2+/-1.5 vs. 5.2+/-3.4 PU.s(-1), p<0.05,
      and 0.95+/-0.6 vs. 1.8+/-1.1 PU.s(-1), p<0.05, respectively). The most pronounced
      impairment of microvascular reactivity was present in patients with combination
      of arterial hypertension and diabetes mellitus.

PMID- 17223726
TI  - Plasma tissue factor in coronary artery disease: further step to the
      understanding of the basic mechanisms of coronary artery thrombosis.
AB  - Tissue factor is a cell surface protein that is expressed constitutively by
      monocytes, macrophages and fibroblasts, but also by some other cells in response
      to a variety of stimuli. The main function of the tissue factor is to form a
      complex with factor VII/VIIa that converts factors IX and X to their active
      forms. Tissue factor is also involved in the pathophysiology of systemic
      inflammatory disorders, coagulopathies, atherosclerotic disease, tumor
      angiogenesis and metastasis. Increased tissue factor expression either locally in
      the coronary plaques or systematically on circulating blood elements of patients
      with acute coronary syndromes may be responsible for increased thrombin
      generation, thus leading to platelet activation and fibrin formation. Tissue
      factor therefore plays a pivotal role in the initiation of thrombotic
      complications in patients with coronary artery disease.

PMID- 17223727
TI  - Comparative analysis of tryptophan oxygenase activity and glucocorticoid receptor
      under the influence of insulin.
AB  - This investigation addresses the interaction of insulin (INS) and glucocorticoid
      (GC) signaling in the hepatic regulation of tryptophan oxygenase (TO) enzyme
      activity in the rat. Male Wistar rats (200-250 g b.w) received an injection of
      the different doses of INS (10, 25, 50, 70 and 100 microg/200 g b.w., i.p.) and
      were used for experiments 3 h and 18 h after INS administration. This study shows
      that maximum of TO activity was found at dose of 50 microg of INS with peak
      increases observed at 3 h and 18 h after injection of INS, while INS had no
      effect on TO activity in adrenalectomized rats. The analysis of INS effects on
      glucocorticoid receptor-complex (GC/GR complex) stability shows that complexes
      from INS-treated rats are less stable than those from control animals. In
      addition, INS-stimulated stability of glucocorticoid receptor (GR) protein was
      significantly increased from the controls. Furthermore, the results show that
      GC/GR complexes from INS-treated rats could be activated and accumulated at
      higher rate in cell nuclei of control animals. These data support the involvement
      of INS in modulation of GC signaling pathway which mediates, in part, the
      activity of TO.

PMID- 17223728
TI  - Pregnancy-associated plasma protein A and proform eosinophilic major basic
      protein in the detection of different types of coronary artery disease.
AB  - Kryptor system was proven to be a rapid, standard method for pregnancy-associated
      plasma protein A and proform eosinophilic major basic protein (PAPP-A/proMBP)
      complex detection in coronary artery disease (CAD). No age and/or gender
      differences in 51 controls and 110 stable coronary artery disease (SCAD) patients
      were found. SCAD patients did not differ from controls and no difference in PAPP
      A/proMBP levels with regards to the number of affected vessels was found. In 21
      unstable angina pectoris (UAP), in 35 without and 66 with ST elevation acute
      myocardial infarctions (NSTEMI, STEMI respectively) patients PAPP-A/proMBP levels
      were increased (P=0.004 and P<0.0005, respectively). PAPP-A/proMBP levels did not
      correlate with cardiac troponin I (cTnI) in STEMI and NSTEMI patients. PAPP-A/
      proMBP increase was more frequent than cTnI (P=0.036) within the early phase of
      STEMI. In NSTEMI patients PAPP-A/proMBP positivity was present in 50% of cTnI
      negative cases. Receiver operating characteristic (ROC) analysis revealed the
      highest diagnostic accuracy of PAPP-A/proMBP (0.919) in STEMI cTnI positive
      cases. The highest specificity/sensitivity PAPP-A/proMBP levels for particular
      acute coronary syndrome (ACS) types were 10.65-14.75 mIU/l. Combination of PAPP
      A/proMBP with cTnI increases their diagnostic efficacy within the early phase of
      ACS. Our results suggest that PAPP-A/proMBP complex is involved in processes
      preceding vulnerable plaque development in ACS.

PMID- 17223729
TI  - Adaptation of the heart to hypertension is associated with maladaptive gap
      junction connexin-43 remodeling.
AB  - We hypothesized that hypertension-related myocardial remodeling characterized by
      hypertrophy and fibrosis might be accompanied by cell-to-cell gap junction
      alterations that may account for increased arrhythmogenesis. Intercellular
      junctions and expression of gap junction protein connexin-43 were analyzed in rat
      heart tissues from both spontaneous (SHR) and L-NAME model of hypertension.
      Isolated heart preparation was used to examine susceptibility of the heart to
      lethal ventricular fibrillation induced by low potassium perfusion.
      Ultrastructure observation revealed enhanced neoformation of side-to-side type
      while internalization of end-to-end type (intercalated disc-related) of gap
      junctions prevailed in the myocardium of rats suffering from either spontaneous
      or L-NAME-induced hypertension. In parallel, immunolabeling showed increased
      number of connexin-43 positive gap junctions in lateral cell membrane surfaces,
      particularly in SHR. Besides, focal loss of immunopositive signal was observed
      more frequently in hearts of rats treated with L-NAME. There was a significantly
      higher incidence of hypokalemia-induced ventricular fibrillation in hypertensive
      compared to normotensive rat hearts. We conclude that adaptation of the heart to
      hypertension-induced mechanical overload results in maladaptive gap junction
      remodeling that consequently promotes development of fatal arrhythmias.

PMID- 17223730
TI  - Early and late effects of hyperbaric oxygen treatment on oxidative stress
      parameters in diabetic patients.
AB  - Exposure to hyperbaric oxygen leads to increased amount of reactive oxygen
      species (ROS) that are derived from various sources. After the discovery that ROS
      can function as signaling molecules, the idea of ROS being hazardous to
      biological tissues has been challenged. The aim of this study was to examine the
      changes in oxidative stress parameters in diabetics undergoing hyperbaric oxygen
      therapy (HBOT) due to foot ulcers. Twenty patients, who received HBOT for
      diabetic foot ulcers, were included in the study. Blood samples were taken before
      HBOT and 30 min after exit from the chamber, on the day of the first and the
      fifteenth HBOT sessions. They were used for the determinations of malondialdehyde
      (MDA), 8-isoprostane and advanced oxidation protein products (AOPPs). 8
      Isoprostane and AOPP levels were not altered significantly after the first HBOT
      session, while both were increased on the fifteenth day (p<0.05). MDA was
      significantly increased only after the first HBOT session, and remained unchanged
      on the fifteenth day (within-day variations). Plasma AOPP levels were lowered
      significantly after fifteen consecutive HBOT sessions (between-day variations).
      Decreased AOPP levels suggest that increased oxygenation of tissues due to HBO
      therapy may activate some endogenous factors that prevent hazardous effects of
      the disease itself.

PMID- 17223731
TI  - Morphological changes in the hippocampus following nicotine and kainic acid
      administration.
AB  - Using histochemical analysis (NADPH-diaphorase, Fluoro-Jade B dye and bis
      benzimide 33,342 Hoechst) we studied the influence of intraperitoneal
      administration of nicotine (NIC), kainic acid (KA) and combination of both these
      substances on hippocampal neurons and their changes. In experiments, 35-day-old
      male rats of the Wistar strain were used. Animals were pretreated with 1 mg/kg of
      nicotine 30 min prior to the kainic acid application (10 mg/kg). After two days,
      the animals were transcardially perfused with 4 % paraformaldehyde under deep
      thiopental anesthesia. Cryostat sections were stained to identify NADPH
      diaphorase positive neurons that were then quantified in the CA1 and CA3 areas of
      the hippocampus, in the dorsal and ventral blades of the dentate gyrus and in the
      hilus of the dentate gyrus. Fluoro-Jade B positive cells were examined in the
      same areas in order to elucidate a possible neurodegeneration. In animals exposed
      only to nicotine the number of NADPH-diaphorase positive neurons in the CA3 area
      of the hippocampus and in the hilus of the dentate gyrus was higher than in
      controls. In contrast, KA administration lowered the number of NADPH-diaphorase
      positive cells in all studied hippocampal areas and in both blades of the dentate
      gyrus. Massive cell degeneration was observed in CA1 and CA3 areas of the
      hippocampus and in the hilus of the dentate gyrus after kainic acid
      administration. Animals exposed to kainic acid and pretreated with nicotine
      exhibited degeneration to a lesser extent and the number of NADPH-diaphorase
      positive cells was higher compared to rats, which were exposed to kainic acid
      only.

PMID- 17223732
TI  - Association of gestational diabetes mellitus and low-density lipoprotein (LDL)
      particle size.
AB  - A predominance of small, dense low-density lipoproteins (LDL) is characteristic
      of the dyslipidemic state seen in type 2 diabetes. However, no study has
      investigated the association in gestational diabetes mellitus (GDM), which is
      pathophysiologically similar to type 2 diabetes. We hypothesized that LDL
      particle size is reduced in GDM cases compared with controls. Gradient gel
      electrophoresis was used to characterize LDL subclass phenotypes in non-fasting
      intrapartum plasma from 105 GDM cases and 96 controls. All participants were free
      of pre-existing diabetes or hypertension. The authors used logistic regression to
      estimate odds ratios (OR) and 95 % confidence intervals (CI) adjusted for
      confounders. Women with this phenotype had a significant 4.9-fold (95 % CI: 1.1
      23.2) increased risk of GDM compared with those with the large, buoyant
      phenotype. The magnitude of this association was attenuated when plasma
      triglyceride and other confounders were included in the model (OR=4.2, 95 % CI:
      0.5-39.5). Mean LDL particle size in GDM cases was smaller compared with controls
      (270.1 vs. 272.7A, p=0.003). The OR of GDM risk was 1.8 (95 % CI: 0.9-3.3) for
      every 10-A reduction in LDL particle size. Large prospective studies are needed
      to evaluate the association between smaller LDL particle size in early pregnancy
      with subsequent GDM risk.

PMID- 17223734
TI  - Discarded stem cells with a future?
AB  - Although embryonic stem cells hold the promise for tissue and organ generation,
      stem cells with early mesenchymal character, which can be obtained at the time of
      birth from extra-embryonic tissue, may have similar capabilities if manipulated
      appropriately. These 'perinatal' tissues, such as the umbilical cord or the
      placenta, which are generally discarded after delivery, contain early mesenchymal
      stem cells that are believed to have a greater potential for plasticity than
      postnatal mesenchymal cells, such as those from bone marrow. They express early
      transcriptional genes, and emerging technologies, such as nuclear reprogramming,
      could direct their development into tissues of embryonic origin. Hence, these
      cells, generally discarded after birth, could become a valuable source for future
      tissue generation.

PMID- 17223733
TI  - Compensatory recovery of vagal control of hemodynamics after unilateral vagotomy.
AB  - This study investigated whether each part of the heart is evenly innervated by
      the left or right vagus and observed the mechanism of compensatory recovery after
      unilateral cervical vagotomy. HR, BP, LVSP and +/-dp/dt max all decreased one
      week after left vagotomy, whereas only BP and -dp/dt max decreased one week after
      right vagotomy. Western blot analyses revealed that the expression of M(2)
      receptors in the left atrium and left ventricle was upregulated after subacute (1
      week) left/right vagotomy. However, significantly more cholinesterase-positive
      nerves in LV and RV were seen one week after unilateral vagotomy compared to the
      sham-operated group. In addition, baroreflex sensitivity was increased after
      subacute right vagotomy. The decreasing effects of ACh (0.5 microg/kg) on LVSP
      and +/-dp/dt max (but not on HR and BP) were facilitated by subacute unilateral
      vagotomy. Our present experiments indicate that 1) the working myocardium is
      innervated bilaterally by the vagus, 2) ventricular contractility is influenced
      more by denervation of the left than the right vagus and 3) up-regulation of M(2)
      muscarinic receptors in the left heart, increase of cholinergic nerves, and high
      baroreflex sensitivity could be involved in the mechanism of compensatory
      hemodynamic recovery via contralateral vagus overactivity, thereby amplifying
      contralateral vagal activity and decreasing cardiac contractility.

PMID- 17223735
TI  - Immunomodulatory neural stem cells for brain tumour therapy.
AB  - Advances in the understanding of stem cells have enabled the development of novel
      therapies for brain tumours. Neural stem cells (NSCs) possess the ability to
      migrate throughout the CNS. By exploiting the tropism of NSCs to various neural
      pathologies (e.g., glioma, degeneration, stroke and so on) and the delivery of
      various immunomodulatory cytokines, new treatments for brain tumours have been
      investigated. These new strategies offer significantly more specificity than
      existing treatment regimens, such as surgery, radiation and chemotherapy. As
      methods in isolating and culturing NSCs are better understood, clinical
      applications of this therapeutic strategy may inevitably emerge. Here, the
      preclinical advances and the results supporting the effectiveness of stem cell
      therapies are reviewed. In addition, the obstacles to clinical development and
      methods to circumvent these caveats are discussed.

PMID- 17223736
TI  - Gene therapy for viral hepatitis.
AB  - Hepatitis B and C infections are two of the most prevalent viral diseases in the
      world. Existing therapies against chronic viral hepatitis are far from
      satisfactory due to low response rates, undesirable side effects and selection of
      resistant viral strains. Therefore, new therapeutic approaches are urgently
      needed. This review, after briefly summarising the in vitro and in vivo systems
      for the study of both diseases and the genetic vehicles commonly used for liver
      gene transfer, examines the existing status of gene therapy-based antiviral
      strategies that have been employed to prevent, eliminate or reduce viral
      infection. In particular, the authors focus on the results obtained in clinical
      trials and experimental clinically relevant animal models.

PMID- 17223737
TI  - AAV-mediated gene transfer for retinal diseases.
AB  - Vectors based on the adeno-associated virus (rAAV) are able to transduce the
      retina of animal models, including non-human primates, for a long-term period,
      safely and at sustained levels. The ability of the various rAAV serotypes to
      transduce retinal target cells has been exploited to successfully transfer genes
      to photoreceptors, retinal pigment epithelium and the inner retina, which are
      affected in many inherited and non-inherited blinding diseases. rAAV-mediated,
      constitutive and regulated gene expression at therapeutic levels has been
      achieved in the retina of animal models, thus providing proof-of-principle of
      gene therapy efficacy and safety in models of dominant and recessive retinal
      disorders. In addition, gene transfer of molecules with either neurotrophic or
      antiangiogenic properties provides useful alternatives to the classic gene
      replacement for treatment of both mendelian and complex traits affecting the
      retina. Years of successful rAAV-mediated gene transfer to the retina have
      resulted in restoration of vision in dogs affected with congenital blindness.
      This has paved the way to the first attempts at treating inherited retinal
      diseases in humans with rAAV. Although the results of rAAV clinical trials for
      non-retinal diseases give a warning that the outcome of viral-mediated gene
      transfer in humans may be different from that predicted based on results in other
      species, the immune privilege of the retina combined with the versatility of rAAV
      serotypes may ultimately provide the first successful treatment of human
      inherited diseases using rAAV.

PMID- 17223738
TI  - Cysteine cathepsins: regulators of antitumour immune response.
AB  - Cysteine cathepsins are lysosomal cysteine proteases that are involved in a
      number of important biological processes, including intracellular protein
      turnover, propeptide and hormone processing, apoptosis, bone remodelling and
      reproduction. In cancer, the cathepsins have been linked to extracellular matrix
      remodelling and to the promotion of tumour cell motility, invasion, angiogenesis
      and metastasis, resulting in poor outcome of cancer patients; however, cysteine
      cathepsins are also involved at different levels of the innate and adaptive
      immune responses. Their best known role in this aspect is their contribution to
      major histocompatibility complex class II antigen presentation, the processing of
      progranzymes into proteolytically active forms, cytotoxic lymphocyte self
      protection, cytokine and growth factor degradation and, finally, the induction of
      cytokine expression and modulation of integrin function. This review is focused
      on the role of cysteine cathepsins in the antitumour immune response and the
      evaluation of their pro- and anticancer behaviours during the regulation of these
      processes.

PMID- 17223739
TI  - Ii-Key/MHC class II epitope hybrids: a strategy that enhances MHC class II
      epitope loading to create more potent peptide vaccines.
AB  - Life-threatening diseases, such as cancer and pandemic influenza, demand new
      efforts towards effective vaccine design. Peptides represent a simple, safe and
      adaptable basis for vaccine development; however, the potency of peptide vaccines
      is insufficient in most cases for significant therapeutic efficacy. Several
      methods, such as Ligand Epitope Antigen Presentation System and ISCOMATRIX, have
      been developed to enhance the potency of peptide vaccines. One way of increasing
      the loading of MHC class II peptides occurs through the use of Ii-Key technology.
      Ii-Key (LRMK), a portion of the MHC class II-associated invariant chain (Ii),
      facilitates the direct loading of epitopes to the MHC class II molecule groove.
      Linking the Ii-Key moiety via a simple polymethylene bridge to an MHC class II
      epitope, to generate an Ii-Key/MHC class II epitope hybrid, greatly enhances the
      vaccine potency of the tethered epitope. The combination of such Ii-Key/MHC class
      II epitope hybrids with MHC class I epitope-containing peptides might generate a
      potent peptide vaccine for malignancies and infectious diseases. The Ii-Key
      hybrid technology is compared with other methods that enhance the potency of a
      peptide vaccine.

PMID- 17223740
TI  - Potential use of IL-2/anti-IL-2 antibody immune complexes for the treatment of
      cancer and autoimmune disease.
AB  - Initially discovered as a potent T cell proliferation factor, IL-2 was soon used
      for cancer immunotherapy, especially for metastatic melanoma and renal cell
      carcinoma; however, the severe side effects of IL-2 therapy, plus the negative
      role of IL-2 in maintaining of CD4+ CD25+ T regulatory cells (Tregs), has
      somewhat dampened enthusiasm for using IL-2 in immunotherapy. This opinion
      article discusses the possibility of combining IL-2 with certain anti-IL-2
      antibodies for reducing the dose of IL-2 needed and preferentially stimulating
      effector T cells, but not Tregs, an approach that might provide an improved
      strategy for anticancer immunotherapy. Alternatively, complexes of IL-2 with
      other anti-IL-2 antibodies can selectively stimulate Tregs and could, therefore,
      be useful for treating autoimmune diseases.

PMID- 17223741
TI  - Zoledronic acid in the management of metastatic bone disease.
AB  - Bisphosphonate therapy has become a standard of therapy for patients with
      malignant bone disease. Moreover, in vivo preclinical and preliminary clinical
      data suggest that bisphosphonates may prevent cancer treatment-induced bone loss
      and the onset of malignant bone disease in patients with early-stage cancer. This
      comprehensive review critically reports the several preclinical evidences of
      action of bisphosphonates on osteoclasts, lymphocytes and tumour cells. In
      addition, all the clinical trials evaluating the effects of principal
      bisphosphonates on skeletal disease progression in patients with breast cancer,
      prostate cancer, non-small cell lung cancer and other cancers have been reported.
      Of the available bisphosphonates, intravenous zoledronic acid has demonstrated
      the broadest clinical activity and is actually approved for the treatment of bone
      metastases from any solid tumour in many countries. Renal safety is an important
      consideration for oncologists who are treating patients with bisphosphonates.
      This issue and the other topics relating to the safety of bisphosphonates are
      discussed in this review.

PMID- 17223742
TI  - Adalimumab for rheumatoid arthritis.
AB  - In the last few years significant advances have been made in our understanding of
      the molecular mechanisms underlying rheumatoid arthritis pathogenesis. Pro
      inflammatory cytokines, such as TNF-alpha, play a pivotal role in its
      pathogenesis. Anti-TNF-alpha biological agents are considered a major advance in
      the treatment of rheumatoid arthritis. Adalimumab is a fully human monoclonal
      antibody that binds specifically to TNF-alpha, thereby neutralising its activity.
      It had significant efficacy in well-designed, placebo-controlled trials in
      patients suffering from rheumatoid arthritis, both as monotherapy and in
      combination with various disease-modifying antirheumatic drugs, including
      methotrexate. Adalimumab was generally well tolerated during both concomitant
      therapy with methotrexate or standard antirheumatic therapy and monotherapy. In
      addition, the radiographic progression of structural joint damage was
      significantly inhibited by adalimumab and improved quality of life. This review
      summarises the recent available data.

PMID- 17223743
TI  - Alfimeprase: a novel recombinant direct-acting fibrinolytic.
AB  - Alfimeprase is a recombinant, direct-acting fibrinolytic zinc metalloprotease.
      Alfimeprase has direct proteolytic activity primarily against the fibrin(ogen)
      Aalpha chain. Alfimeprase is covalently bound and neutralised by serum alpha(2)
      macroglobulin, a prevalent mammalian protease inhibitor. Preclinical pharmacology
      studies have shown that fibrinolysis with alfimeprase is up to sixfold more rapid
      than with select plasminogen activators, such as tissue-type plasminogen
      activator and urokinase. Alfimeprase directly delivered to a site of thrombosis
      has the potential to be a fast and effective fibrinolytic, which does not
      generate the systemic lytic state seen with plasminogen activators that is
      associated with major bleeding, including intracerebral haemorrhage. Phase I and
      II studies in individuals with arterial or venous thrombotic events indicate that
      alfimeprase is active and generally well tolerated.

PMID- 17223744
TI  - Comparison of hydrogels in the in vivo formation of tissue-engineered bone using
      mesenchymal stem cells and beta-tricalcium phosphate.
AB  - Availability of grafts and morbidity at the donor site limit autologous
      transplantation in patients requiring bone reconstruction. A tissue-engineering
      approach can overcome these limitations by producing bone-like tissue of custom
      shape and size from isolated cells. Several hydrogels facilitate osteogenesis on
      porous scaffolds; however, the relative suitability of various hydrogels has not
      been rigorously assessed. Fibrin glue, alginate, and collagen I hydrogels were
      mixed with swine bone marrow-derived differentiated mesenchymal stem cells
      (MSCs), applied to 3-dimensionally printed porous beta-tricalcium phosphate (beta
      TCP) scaffolds and implanted subcutaneously in nude mice. Although noninvasive
      assessment of osteogenesis in 3 dimensions is desirable for monitoring new bone
      formation in vivo, correlations with traditional histological and mechanical
      testing need to be established. High-resolution volumetric computed tomography
      (VCT) scanning, histological examination, biomechanical compression testing, and
      osteonectin (ON) expression were performed on excised scaffolds after 1, 2, 4,
      and 6 weeks of subcutaneous implantation in mice. Statistical correlation
      analyses were performed between radiological density, stiffness, and ON
      expression. Use of collagen I as a hydrogel carrier produced superior bone
      formation at 6 weeks, as demonstrated using VCT scanning with densities similar
      to native bone and the highest compression values. Continued contribution of the
      seeded MSCs was demonstrated using swine-specific messenger ribonucleic acid
      probes. Radiological density values correlated closely with the results of
      histological and biomechanical testing and ON expression. High-resolution VCT is
      a promising method for monitoring osteogenesis.

PMID- 17223746
TI  - Getting beyond surgical contraception.

PMID- 17223747
TI  - Thoughts on farm animal welfare.

PMID- 17223748
TI  - What is your diagnosis? Bronchial foreign body.

PMID- 17223749
TI  - What is your diagnosis? Nondisplaced spiral radial fracture.

PMID- 17223750
TI  - Theriogenology question of the month. Neoplasia of the os penis.

PMID- 17223751
TI  - Use of anti-coronavirus antibody testing of cerebrospinal fluid for diagnosis of
      feline infectious peritonitis involving the central nervous system in cats.
AB  - OBJECTIVE: To assess the use of measuring anti-coronavirus IgG in CSF for the
      diagnosis of feline infectious peritonitis (FIP) involving the CNS in cats.
      DESIGN: Prospective study. SAMPLE POPULATION: CSF and serum samples from 67 cats.
      PROCEDURES: CSF and serum samples were allocated into 4 groups: cats with FIP
      involving the CNS (n = 10), cats with FIP not involving the CNS (13), cats with
      CNS disorders caused by diseases other than FIP (29), and cats with diseases
      other than FIP and not involving the CNS (15). Cerebrospinal fluid was evaluated
      for concentrations of erythrocytes, leukocytes, and total protein. Anti
      coronavirus IgG was measured in CSF and serum by indirect immunofluorescence
      assay. RESULTS: CSF IgG (range of titers, 1:32 to 1:4,096) was detected in 12
      cats, including 6 cats with neurologic manifestation of FIP, 4 cats with FIP not
      involving the CNS, and 2 cats with brain tumors. Cerebrospinal fluid IgG was
      detected only in cats with correspondingly high serum IgG titers (range, 1:4,096
      to 1:16,384) and was positively correlated with serum IgG titers (r = 0.652; P <
      0.01), but not with any other CSF parameter. Blood contamination of CSF resulted
      in < or = 333 erythrocytes/microL in cats with CSF IgG. CONCLUSIONS AND CLINICAL
      RELEVANCE: The correlation between serum and CSF IgG and the fact that CSF IgG
      was detected only in strongly seropositive cats suggested that CSF anti
      coronavirus IgG was derived from blood. Measurement of anti-coronavirus IgG in
      CSF was of equivocal clinical use.

PMID- 17223752
TI  - Long-term outcome of juvenile pubic symphysiodesis and triple pelvic osteotomy in
      dogs with hip dysplasia.
AB  - OBJECTIVE: To compare long-term outcomes of juvenile pubic symphysiodesis (JPS)
      and triple pelvic osteotomy (TPO) in dogs with hip dysplasia. DESIGN: Prospective
      clinical trial. ANIMALS: 18 dogs with hip dysplasia (ie, distraction index > or =
      0.5 in at least 1 hip joint and no, mild, or moderate radiographic evidence of
      degenerative joint disease [DJD]). PROCEDURES: Dogs between 4 and 5.5 months old
      at enrollment were assigned to undergo JPS, and dogs between 5 and 12 months old
      were assigned to undergo TPO. All dogs were reexamined at 2 years of age.
      RESULTS: At 2 years of age, there were no significant differences between groups
      in regard to lameness scores, angle of extension of the hip joints, distraction
      index, peak vertical force, acetabular angle, radiographic DJD score, or owner
      assigned scores of clinical function. Dorsal acetabular rim angle was
      significantly higher in dogs that underwent JPS than in dogs that underwent TPO.
      For dogs that underwent TPO, dorsal acetabular rim angle was significantly
      decreased and acetabular angle was significantly increased at 2 years of age,
      compared with values obtained prior to surgery. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that JPS and TPO have similar effects on hip joint
      conformation in dogs with moderate to severe hip dysplasia but that neither
      procedure eliminates the hip joint laxity characteristic of hip dysplasia or the
      progression of degenerative changes.

PMID- 17223753
TI  - Search and identification methods that owners use to find a lost dog.
AB  - OBJECTIVE: To characterize the process by which owners search for lost dogs and
      identify factors associated with time to recovery. DESIGN: Cross-sectional study.
      SAMPLE POPULATION: Owners of 187 dogs lost in Montgomery County, Ohio, between
      June 1 and September 30, 2005. PROCEDURES: A telephone survey was conducted.
      RESULTS: 132 of the 187 (71%) dogs were recovered; median time to recovery was 2
      days (range, 0.5 to 21 days). Dogs were recovered primarily through a call or
      visit to an animal agency (46 [34.8%]), a dog license tag (24 [18.2%]), and
      posting of neighborhood signs (20 [15.2%]). Eighty-nine (48%) dogs had some type
      of identification at the time they were lost (ie, identification tag, dog license
      tag, rabies tag, or microchip). Owners had a higher likelihood of recovery when
      they called an animal agency (hazard ratio, 2.1), visited an animal agency (1.8),
      and posted neighborhood signs. Dogs that were wearing a dog license tag also had
      a higher likelihood of recovery (hazard ratio, 1.6). Owners were less likely to
      recover their dogs if they believed their dogs were stolen (hazard ratio, 0.3).
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that various factors are
      associated with the likelihood that owners will recover a lost dog. Both animal
      agencies and veterinarians can play a role in educating dog owners on the
      importance of identification tags, licensing, and microchips and can help to
      emphasize the importance of having a search plan in case a dog is lost.

PMID- 17223754
TI  - Search and identification methods that owners use to find a lost cat.
AB  - OBJECTIVE: To characterize the process by which owners search for lost cats and
      identify factors associated with time to recovery. DESIGN: Cross-sectional study.
      SAMPLE POPULATION: Owners of 138 cats lost in Montgomery County, Ohio, between
      June 1 and September 30, 2005. PROCEDURES: A telephone survey was conducted.
      RESULTS: 73 of the 138 (53%) cats were recovered; median time to recovery was 5
      days (range, 0.5 to 81 days). Most cats (48 [66%]) that were recovered returned
      home on their own or were found in the neighborhood (5 [7%]); most other cats
      were recovered through posting of neighborhood signs (8 [11%]) or calling or
      visiting an animal agency (5 [7%]). The highest success rate for any of the
      search methods that were used was only 12% (posting neighborhood signs). Only 26
      of the 138 (19%) cats had some type of identification at the time they were lost
      (ie, identification tag, rabies tag, or microchip). Owners allowed 82 (59%) cats
      to spend at least some time outdoors. The percentage of sexually intact cats
      recovered by their owners (4/16 [25%]) was significantly lower than the
      percentage of neutered cats recovered (69/122 [57%]). CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggest that the percentage of lost cats recovered by their
      owners is low, possibly in part because of the lack of use of traditional
      identification methods and the general acceptance that cats may roam.
      Veterinarians can help educate owners about the importance of identification and
      the need to keep cats indoors.

PMID- 17223755
TI  - Prevalence of oxacillin- and multidrug-resistant staphylococci in clinical
      samples from dogs: 1,772 samples (2001-2005).
AB  - OBJECTIVE: To determine whether resistance to oxacillin and other antimicrobials
      in 3 Staphylococcus spp commonly isolated from dogs increased from 2001 to 2005.
      DESIGN: Retrospective case series. SAMPLE POPULATION: 1,772 clinical samples of
      various types obtained from dogs examined at the University of Tennessee
      Veterinary Teaching Hospital or at regional veterinary hospitals and submitted to
      the bacteriology and mycology laboratories associated with the teaching hospital.
      PROCEDURES: Samples were submitted by attending veterinarians to the bacteriology
      and mycology laboratories for routine aerobic microbial culture. Identification
      and antimicrobial susceptibility procedures were performed on all isolates.
      Susceptibility reports for each antimicrobial and Staphylococcus spp were
      determined from aggregate electronically archived test results. Oxacillin and
      multidrug resistance for Staphylococcus intermedius was analyzed by reviewing
      disk diffusion zone measurements. RESULTS: Oxacillin resistance increased among
      S. intermedius isolates during the past 5 years, and the increase was associated
      with multidrug resistance. In 2005, 1 in 5 Staphylococcus spp isolates from
      canine clinical samples was resistant to oxacillin. The most common
      staphylococcal species isolated were S. intermedius (n = 37), Staphylococcus
      schleiferi (21), and Staphylococcus aureus (4), and frequencies of oxacillin
      resistance in isolates of these species were 15.6%, 46.6%, and 23.5%,
      respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Veterinarians should be aware
      of the potential for empiric drug treatment failures in instances where
      Staphylococcus spp infections are common (eg, pyoderma). Judicious use of
      bacterial culture and susceptibility testing is recommended.

PMID- 17223756
TI  - Comparison of core needle biopsy and fine-needle aspiration of enlarged
      peripheral lymph nodes for antemortem diagnosis of enzootic bovine lymphosarcoma
      in cattle.
AB  - OBJECTIVE: To determine whether antemortem core needle biopsy and fine-needle
      aspiration of enlarged peripheral lymph nodes could be used to distinguish
      between inflammation and lymphosarcoma in cattle. DESIGN: Prospective study.
      ANIMALS: 25 cattle with enlarged peripheral lymph nodes. PROCEDURES: Antemortem
      biopsies of the selected lymph nodes were performed with an 18-gauge, 12-cm core
      needle biopsy instrument. Fine-needle aspirates were performed with a 20-gauge, 4
      cm needle. Specimens were analyzed by pathologists who were unaware of clinical
      findings and final necropsy findings, and specimens were categorized as reactive,
      neoplastic, or nondiagnostic for comparison with necropsy results. RESULTS:
      Sensitivity and specificity of core needle biopsy ranged from 38% to 67% and from
      80% to 25%, respectively. Sensitivity of fine-needle aspiration ranged from 41%
      to 53%, and specificity was 100%. Predictive values for positive test results
      ranged from 77% to 89% for core needle biopsy and were 100% for fine-needle
      aspiration. Predictive values for negative test results were low for both core
      needle biopsy and fine-needle aspiration. CONCLUSIONS AND CLINICAL RELEVANCE:
      Results indicated that core needle biopsy and fine-needle aspiration can aid in
      the antemortem diagnosis of bovine enzootic lymphosarcoma. Results of fine-needle
      aspiration of enlarged peripheral lymph nodes were more specific and more
      predictive for a positive test result than were results of core needle biopsy.

PMID- 17223757
TI  - Response of calves to challenge exposure with virulent bovine respiratory
      syncytial virus following intranasal administration of vaccines formulated for
      parenteral administration.
AB  - OBJECTIVE: To determine whether single-fraction and combination modified-live
      bovine respiratory syncytial virus (BRSV) vaccines commercially licensed for
      parenteral administration could stimulate protective immunity in calves after
      intranasal administration. DESIGN: Randomized controlled trial. ANIMALS: 39
      calves. PROCEDURES: Calves were separated from dams at birth, fed colostrum with
      a minimal concentration of antibodies against BRSV, and maintained in isolation.
      In 2 preliminary experiments, 9-week-old calves received 1 (n = 3) or 2 (3) doses
      of a single-component, modified-live BRSV vaccine or no vaccine (8 control calves
      in each experiment), and were challenged with BRSV 21 days after vaccination. In
      a third experiment, 2-week-old calves received combination modified-live virus
      (MLV) vaccines with or without BRSV and calves were challenged with BRSV 8 days
      later. Calves were euthanized, and lung lesions were measured. Immune responses,
      including serum and nasal antibody and nasal interferon-alpha concentrations,
      were assessed. RESULTS: BRSV challenge induced signs of severe clinical
      respiratory tract disease, including death and pulmonary lesions in unvaccinated
      calves and in calves that received a combination viral vaccine without BRSV.
      Pulmonary lesions were significantly less severe in BRSV-challenged calves that
      received single or combination BRSV vaccines. The proportion of calves that shed
      virus and the peak virus titer was decreased, compared with control calves.
      Protection was associated with mucosal IgA antibody responses after challenge.
      CONCLUSIONS AND CLINICAL RELEVANCE: Single and combination BRSV vaccines
      administered intranasally provided clinical protection and sparing of pulmonary
      tissue similar to that detected in response to parenteral delivery of combination
      MLV and inactivated BRSV vaccines previously assessed in the same challenge
      model.

PMID- 17223759
TI  - Epidemiologic assessment of porcine circovirus type 2 coinfection with other
      pathogens in swine.
AB  - OBJECTIVE: To identify important pathogens and characterize their serologic and
      pathologic effects in porcine circovirus type 2 (PCV2)-infected pigs in relation
      to pig age and type of swine production system. DESIGN: Cross-sectional study.
      ANIMALS: 583 conventionally reared pigs. PROCEDURES: 3- (n = 157), 9- (149), 16-
      (152), and 24-week-old (125) pigs from 41 different 1-, 2-, and 3-site production
      systems (5 pigs/age group/farm) were euthanized and necropsied. Pigs with and
      without PCV2 infection were identified (via PCR assay); infection with and
      serologic responses to other pathogens and pathologic changes in various tissues
      (including lungs) were assessed. Logistic regression models were constructed for
      effects overall and within each age group and type of production system. RESULTS:
      Compared with PCV2-negative pigs, PCV2-positive pigs were more likely to have
      swine influenza virus (SIV) type A and Mycoplasma hyopneumoniae infections and
      sample-to-positive (S:P) ratios for SIV H1N1 from 0.50 to 0.99; also, PCV2
      positive pigs had higher serum anti-porcine reproductive and respiratory syndrome
      virus (PRRSV) antibody titers and more severe lung tissue damage. Infection with
      SIV (but lower SIV H1N1 S:P ratio) was more likely in 3-week-old PCV2-positive
      pigs and evidence of systemic disease was greater in 16-week-old PCV2-positive
      pigs than in their PCV2-negative counterparts. By site type, associations of
      coinfections and disease effects between PCV2-positive and -negative pigs were
      greatest in 3-site production systems. CONCLUSIONS AND CLINICAL RELEVANCE: In
      PCV2-positive pigs, coinfections with SIV, M. hyopneumoniae, and PRRSV are
      important, having the greatest effect in the early to late nursery phase and in 3
      site production systems.

PMID- 17223760
TI  - Product information past perfect.

PMID- 17223761
TI  - Sun protection messages, vitamin D and skin cancer: out of the frying pan and
      into the fire?

PMID- 17223762
TI  - Mycobacterium ulcerans infection (Buruli or Bairnsdale ulcer): challenges in
      developing management strategies.

PMID- 17223763
TI  - Outcomes for Mycobacterium ulcerans infection with combined surgery and
      antibiotic therapy: findings from a south-eastern Australian case series.
AB  - OBJECTIVE: To describe the effect of antibiotics on outcomes of treatment for
      Buruli or Bairnsdale ulcer (BU) in patients on the Bellarine Peninsula in south
      eastern Australia. DESIGN: Observational, non-randomised study with data
      collected prospectively or through medical record review. PATIENTS AND SETTING:
      All 40 patients with BU managed by staff of Barwon Health's Geelong Hospital (a
      public, secondary-level hospital) between 1 January 1998 and 31 December 2004.
      MAIN OUTCOME MEASURES: Epidemiology, clinical presentation, diagnosis, treatment
      and clinical outcomes. RESULTS: There were 59 treatment episodes; 29 involved
      surgery alone, 26 surgery plus antibiotics, and four antibiotics alone. Of 55
      episodes where surgery was performed, minor surgery was required in 22, and major
      surgery in 33. Failure rates were 28% for surgery alone, and 19% for surgery plus
      antibiotics. Adjunctive antibiotic therapy was associated with increased
      treatment success for lesions with positive histological margins (P < 0.01), and
      lesions requiring major surgery for treatment of a first episode (P < 0.01). The
      combination of rifampicin and ciprofloxacin resulted in treatment success in
      eight of eight episodes, and no patients ceased therapy because of side effects
      with this regimen. CONCLUSIONS: Adjunctive antibiotic therapy may increase the
      effectiveness of BU surgical treatment, and this should be further assessed by
      larger randomised controlled trials. The combination of rifampicin and
      ciprofloxacin appears the most promising.

PMID- 17223764
TI  - First case of Mycobacterium ulcerans disease (Bairnsdale or Buruli ulcer)
      acquired in New South Wales.
AB  - Mycobacterium ulcerans is a slow-growing environmental bacterium that causes
      Buruli ulcer (also known as Bairnsdale ulcer in Victoria and Daintree ulcer in
      northern Queensland). We describe two patients with laboratory-confirmed Buruli
      ulcer who were infected either in New South Wales or overseas. A molecular
      epidemiological investigation demonstrated that, while one case was probably
      acquired in Papua New Guinea, the other was most likely to have been acquired in
      southern NSW. To our knowledge, this is the first case of M. ulcerans infection
      acquired in NSW.

PMID- 17223765
TI  - Consensus recommendations for the diagnosis, treatment and control of
      Mycobacterium ulcerans infection (Bairnsdale or Buruli ulcer) in Victoria,
      Australia.
AB  - Mycobacterium ulcerans causes slowly progressive, destructive skin and soft
      tissue infections, known as Bairnsdale or Buruli ulcer (BU). Forty-six delegates
      with experience in the management of BU attended a 1-day conference in Melbourne
      on 10 February 2006, with the aim of developing a consensus approach to the
      diagnosis, treatment and control of BU. An initial draft document was extended
      and improved during a facilitated round table discussion. BU is an environmental
      infection that occurs in specific locations. The main risk factor for infection
      is contact with an endemic area. Prompt cleaning of abrasions sustained outdoors,
      wearing protective clothing, and avoiding mosquito bites may reduce an
      individual's risk of infection. BU can be rapidly and accurately diagnosed by
      polymerase chain reaction testing of ulcer swabs or biopsies. Best outcomes are
      obtained when the diagnosis is made early. To aid early diagnosis, health
      authorities should keep local populations informed of new outbreaks. BU is best
      treated with surgical excision, which, if possible, should include a small rim of
      healthy tissue. For small lesions this may be all that is required. However,
      there is a role for antibiotics for more extensive disease, and their use may
      allow more conservative surgery.

PMID- 17223766
TI  - Iodine status of Tasmanians following voluntary fortification of bread with
      iodine.
AB  - OBJECTIVE: To describe changes in the iodine status of Tasmanians following
      voluntary fortification of bread with iodine in October 2001. DESIGN AND SETTING:
      Post-intervention, cross-sectional urinary iodine surveys of Tasmanian
      schoolchildren aged 8-11 years were used to assess population iodine status.
      Participants were selected using a one-stage cluster sampling method. The
      sampling frame comprised classes containing fourth-grade children from all
      Tasmanian government, Catholic and independent schools. Results were compared
      with pre-intervention survey results. MAIN OUTCOME MEASURES: Median urinary
      iodine concentration (UIC) and percentage of UIC < 50 microg/L ascertained from
      spot urine samples. RESULTS: Median UIC was 75 microg/L in 1998, 72 microg/L in
      2000, 105 microg/L in 2003, 109 microg/L in 2004 and 105 microg/L in 2005. Median
      UIC in post-intervention years (2003-2005) was significantly higher than in pre
      intervention years. The percentage of UIC results < 50 microg/L was 16.9% in
      1998, 18.7% in 2000, 10.1% in 2003, 10.0% in 2004 and 10.5% in 2005. CONCLUSION:
      Despite methodological differences between the pre- and post-intervention
      surveys, switching to iodised salt in bread appears to have resulted in a
      significant improvement in iodine status in Tasmania. Given iodine deficiency has
      been identified in other parts of Australia and in New Zealand, mandatory iodine
      fortification of the food supply in both countries is worthy of consideration. As
      voluntary fortification relies on industry goodwill, mandating fortification
      could be expected to enhance population reach and give a greater guarantee of
      sustainability in Tasmania.

PMID- 17223767
TI  - "Not-for-resuscitation" orders in Australian public hospitals: policies,
      standardised order forms and patient information leaflets.
AB  - OBJECTIVE: To determine the prevalence and content of policies, standardised
      order forms (SOFs) and patient information leaflets (PILs) pertaining to "not-for
      resuscitation" (NFR) orders in Australian public hospitals. DESIGN AND SETTING:
      Cross-sectional postal survey conducted across Australia from August to December
      2005, using a one-page questionnaire. PARTICIPANTS: Directors of Medical, Nursing
      or Clinical Services of all public hospitals in Australia with 60 or more beds,
      excluding psychiatric, military and private hospitals. MAIN OUTCOME MEASURES:
      Prevalence of documented NFR policies, by hospital characteristics, and content
      of these policies, SOFs and PILs. RESULTS: 222 hospitals were surveyed, and 157
      responded (71%). Of these, 85 (54%) had NFR policies, 62 (39%) had SOFs, and four
      (3%) had PILs. Hospitals with more than 200 beds were more likely to have NFR
      policies than those with 60-200 beds (P = 0.04). More metropolitan than rural
      hospitals had NFR policies (P = 0.01). More hospitals with 60-100 beds had SOFs
      than hospitals with 101-200 beds (P = 0.03). "NFR" was defined in 53% of
      policies, while 97% of policies explicitly stated where NFR orders were to be
      documented, 89% stated who was allowed to make them, 37% stated that advanced
      care directives ("living wills") were to be respected, and 89% stated that
      competent patients should be involved in discussions regarding their NFR status.
      The most common items noted in SOFs were the name and signature of the issuing
      medical practitioner (92%) and documentation of the discussion with the patient
      (81%). CONCLUSIONS: There was wide variation in the content of hospital policies,
      SOFs and PILs pertaining to NFR orders. Aspects of current policies show room for
      improvement.

PMID- 17223769
TI  - In the wake of hospital inquiries: impact on staff and safety.
AB  - Mishandled concerns about clinical standards resulted in whistleblowing in four
      Australian hospitals. Official inquiries followed with recommendations to improve
      patient safety. In the aftermath of the inquiries, common themes included loss of
      trust in management and among clinical colleagues, and loss of trust from
      patients and the community. Without first rebuilding trust, staff will not report
      mistakes or other concerns about safety. Successful implementation of patient
      safety procedures requires policies to stress the professional duty of staff to
      report concerns about colleagues when they believe there is a risk to patients.

PMID- 17223768
TI  - Barriers in the quest for quality drug information: salutary lessons from TGA
      approved sources for thyroid-related medications.
AB  - Product information (PI) for thyroid-related medications endorsed by the
      Therapeutic Goods Administration, as reproduced in the commonly used compilation
      publications June 2006 MIMS (Monthly index of medical specialties) annual, MIMS
      Online and the Australian prescription products guide 2006, was evaluated to see
      whether it reflects contemporary therapeutic practice. Compared with current
      medical literature, these PI-based sources provide inadequate, inaccurate or
      outdated therapeutic directives. Examples include: Incorrect advice that
      thyroxine therapy should always begin at very low dosage. Failure to recommend
      increased thyroxine dosage early in pregnancy (thus placing the offspring of
      women being treated for hypothyroidism at risk of impaired fetal brain
      development). Incorrect and potentially unsafe advice to treat thyrotoxicosis
      with stable iodide in late pregnancy. Failure to advise serial adjustment of
      antithyroid drug dosage until after a patient becomes euthyroid (this can result
      in iatrogenic thyroid dysfunction). Outdated advice that antithyroid drugs are
      not compatible with breastfeeding. Recent initiatives to upgrade consumer
      medicine information (CMI) appear to accept PI-based sources as a reliable
      benchmark for CMI. That inference is not warranted for thyroid-related
      medications. Accountability for the updating of clinical information in PI needs
      to be defined, and the process for updating PI may need to be modified. Quality
      drug information, both PI and CMI, depends on fluent, evidence-based
      collaboration between suppliers, regulators, prescribers, specialist clinicians
      and consumers.

PMID- 17223770
TI  - Chronic disease self-management education programs: challenges ahead.
AB  - Chronic disease self-management education programs aim to empower patients
      through providing information and teaching skills and techniques to improve self
      care and doctor-patient interaction, with the ultimate goal of improving quality
      of life. The recent 2006-07 federal budget allocated an unprecedented $515
      million over 5 years for activation of patient self-management activities,
      commencing this financial year. Previous attempts in other countries to
      incorporate self-management education activities into the health care sector have
      faced setbacks because of inadequate integration into primary care. Engagement of
      health care professionals and their endorsement of self-management activities is
      critical to success.

PMID- 17223771
TI  - Waiver of individual patient consent in research: when do potential benefits to
      the community outweigh private rights?
AB  - Health services research is important to ensure continued best quality of care,
      but often uses data obtained without explicit consent for this purpose. Obtaining
      consent may be difficult for many reasons, but excluding individuals may
      introduce biases that alter the significance of studies. Approval by ethics
      committees of a waiver of the need for consent allowed our study to proceed and
      provide evidence that has led to the implementation of a population-based
      screening policy for the prospective detection of hereditary non-polyposis
      colorectal cancer. This screening policy has resulted in more cases being
      detected routinely with better management for affected patients and their at-risk
      families. A need for consent would have prohibited this study, and the
      development of a more efficient screening policy could have been delayed for
      several more years. Ethics committees can effectively manage the need to uphold
      basic ethical principles without unnecessarily impeding socially useful research.
      Committees need to be familiar with the guidelines approved under sections 95 and
      95A of the Privacy Act 1988 (Cwlth) in addition to the National Health and
      Medical Research Council National statement on ethical conduct in research
      involving humans.

PMID- 17223772
TI  - Potential link between HMG-CoA reductase inhibitor (statin) use and interstitial
      lung disease.
AB  - Over a 3-year period, seven patients who were taking HMG-CoA reductase inhibitors
      (statins) presented to our respiratory service with interstitial pneumonitis.
      Clinical course varied, with the condition responding to prednisolone treatment
      and cessation of statins in three patients, and progressing slowly despite this
      management in another three, while one patient died of associated cardiac
      disease. While a causative role cannot be confirmed, clinicians should be aware
      of the possible association.

PMID- 17223773
TI  - Should medical students be routinely offered BCG vaccination?

PMID- 17223774
TI  - Does the presence of heart failure alter prescribing of drug therapy after
      myocardial infarction?

PMID- 17223775
TI  - Lung encasement by metastatic osteoblastic sarcoma.

PMID- 17223776
TI  - Guidelines for the management of acute coronary syndromes 2006.

PMID- 17223777
TI  - Conundrums in community-acquired pneumonia.

PMID- 17223778
TI  - Chronic disease self-management education programs: challenges ahead.

PMID- 17223779
TI  - Trehalose accumulation in a high-trehalose-accumulating mutant of
      Saccharomycopsis fibuligera sdu does not respond to stress treatments.
AB  - The isolation of high-trehalose-accumulating mutant A11 from Saccharomycopsis
      fibuligera sdu has been previously described. In this paper, accumulation of
      trehalose under various stress conditions in S. fibuligera A11 was investigated.
      Neither activation of trehalose-6-phosphate synthase (SfTps1) nor change in
      trehalose content was observed under stress exposure of S. fibuligera A11 cells.
      A fragment of the Sftps1 gene in this strain was also cloned by degenerate PCR
      using the CoDeHOP strategy and multiply-aligned Tps1 sequences. This sequence
      allowed us to investigate the expression of the Sftps1 gene, which was also kept
      constant under the various stress conditions. Altogether, these results indicate
      that trehalose metabolism in S. fibuligera A11 in response to stress conditions
      clearly differs from that of Saccharomyces cerevisiae and most other fungi. The
      expression of the Sftps1 gene was not responsive to different stress treatments.

PMID- 17223780
TI  - Protein refolding assisted by molecular tube based alpha-cyclodextrin as an
      artificial chaperone.
AB  - In this study, we evaluated, for the first time, the application of molecular
      tube based alpha-cyclodextrin for improving the refolding yields of two different
      enzymes: carbonic anhydrase and alkaline phosphatase. Our results indicate that
      under the optimal developed refolding environments, the denatured carbonic
      anhydrase and alkaline phosphatase were refolded with a yield of 51 and 61% using
      15 and 5 mg/ml of the molecular tube, respectively. Regardless of lower refolding
      yields compared with liquid-phase artificial chaperone assisted approach, the new
      technique (solid-phase artificial chaperone assisted refolding) benefits from
      easier and faster separation of the refolded product from the refolding
      environment, recycling of the stripping agent, and finally, significantly less
      environmental effect at the industrial levels. However, further improvements in
      solid-phase artificial chaperone assisted technique are needed either through
      synthesizing better stripping agents or by optimizing and defining better
      refolding environments.

PMID- 17223781
TI  - Dimerization properties of Rabaptin-5 and its isoforms.
AB  - Rabaptin-5 plays an important role in intracellular membrane traffic acting as an
      effector molecule of small GTPases Rab5 and Rab4. It was previously demonstrated
      that Rabaptin-5 exists as a part of a large protein complex in vivo and is able
      to form dimers in vitro. Data of X-ray structural analysis suggest that
      dimerization of Rabaptin-5 is an important feature required for its interaction
      with Rab5 GTPase. Recently several isoforms of Rabaptin-5 characterized by
      various deletions in the polypeptide chains have been identified. These isoforms
      might exhibit functional properties that differ from those of Rabaptin-5. In this
      study, we have investigated dimerization properties of delta and gamma isoforms
      of Rabaptin-5. In addition, we have provided the first direct evidence for
      Rabaptin-5 dimerization in cells.

PMID- 17223782
TI  - Cytotoxicity effect of algal polysaccharides on HL60 cells.
AB  - The present study shows the cytotoxic effect of three different classes of algal
      polysaccharides on HL60 cells. Three galactofucans, fucoidan, and glucan were the
      polysaccharides utilized in this analysis. The parameters used for evaluating
      cell viability were [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide] (MTT) reduction, protein content, and phosphatase activity. We
      demonstrated stimulation of phosphatase activity, MTT reduction, and protein
      content in relation to three types of galactofucans (1, 2, and 3) with different
      molecular weights (1600, 1200, and 360 kD). However, when HL60 cells were treated
      with galactofucan type 3, the total protein remained unchanged. Under the same
      experimental conditions, an expressed increase in the phosphatase activity was
      detected when galactofucan 3 was utilized. In relation to the mitochondrial
      function, the stimulation was higher in cells treated with galactofucan type 1.
      Fucoidan did not have a significant effect on MTT reduction, but protein content
      was decreased (IC50 around 30 microg/ml). Glucan also activated all the
      parameters that were analyzed, and this effect was more expressed in the
      phosphatase activity and in the protein content. This study provides new insights
      into the cytotoxic action of polysaccharides on HL60 cells and suggests for the
      first time the possible involvement of phosphatases in this process.

PMID- 17223783
TI  - Specificity of catechol ortho-cleavage during para-toluate degradation by
      Rhodococcus opacus 1cp.
AB  - Degradation of para-toluate by Rhodococcus opacus 1cp was investigated.
      Activities of the key enzymes of this process, catechol 1,2-dioxygenase and
      muconate cycloisomerase, are detected in this microorganism. Growth on p-toluate
      was accompanied by induction of two catechol 1,2-dioxygenases. The substrate
      specificity and physicochemical properties of one enzyme are identical to those
      of chlorocatechol 1,2-dioxygenase; induction of the latter enzyme was observed
      during R. opacus 1cp growth on 4-chlorophenol. The other enzyme isolated from the
      biomass grown on p-toluate exhibited lower rate of chlorinated substrate cleavage
      compared to the catechol substrate. However, this enzyme is not identical to the
      catechol 1,2-dioxygenase cloned in this strain within the benzoate catabolism
      operon. This supports the hypothesis on the existence of multiple forms of
      dioxygenases as adaptive reactions of microorganisms in response to environmental
      stress.

PMID- 17223784
TI  - Immobilizing Cu,Zn-superoxide dismutase in hydrogels of carboxymethylcellulose
      improves its stability and wound healing properties.
AB  - Hydrogels of carboxymethylcellulose (CMC) with 50 and 90% cross-linking degree
      (CMC50% and CMC90%, respectively) were prepared and loaded with bovine
      erythrocyte Cu,Zn-superoxide dismutase (SOD) to obtain two drug delivery systems:
      SOD-CMC50% and SOD-CMC90%. Resistance of native SOD to inactivation by H2O2 and
      the effect of applying SOD-CMC hydrogels to open wounds of rats' back skin were
      examined and compared to that of SOD trapped into CMC50% and CMC90% hydrogels.
      Also, the effect of CMC50% and SOD-CMC90% on human fibroblasts proliferation was
      evaluated at different times. It was found that SOD in the hydrogel was more
      resistant to H2O2 inactivation than the native enzyme and at the same time it
      reduced the time necessary for wound healing. Furthermore, the highest cell
      proliferation value was found for the CMC50% hydrogels, which had a three
      dimensional structure suitable for gas and nutrient exchanges and improving cell
      life conditions.

PMID- 17223785
TI  - Optimization of solubilization and purification procedures for the hydroxylase
      component of membrane-bound methane monooxygenase from Methylococcus capsulatus
      strain M.
AB  - The hydroxylase component of membrane-bound (particulate) methane monooxygenase
      (pMMO) from Methylococcus capsulatus strain M was isolated and purified to
      homogeneity. The pMMO molecule comprises three subunits of molecular masses 47,
      26, and 23 kD and contains three copper atoms and one iron atom. In solution the
      protein exists as a stable oligomer of 660 kD with possible subunit composition
      (alpha beta gamma)6. Mass spectroscopy shows high homology of the purified
      protein with methane monooxygenase from Methylococcus capsulatus strain Bath.
      Pilot screening of crystallization conditions has been carried out.

PMID- 17223786
TI  - Effect of succinylation of antibodies on their conformation and interaction with
      the antigen.
AB  - Using succinic anhydride, a succinylated derivative of anti-urease IgG having 49
      +/- 6% modification was prepared and its physicochemical and immunological
      properties were studied. IgG undergoes substantial changes in its native
      conformation on succinylation, which was mainly attributed to electrostatic
      destabilization of the native protein conformation. The modified IgG exhibited a
      decrease in its cross-reactivity with urease. This decrease is attributed to the
      conformational change in IgG upon succinylation and/or is due to the disruption
      of the lysine residues in the antigen-binding site of IgG upon succinylation,
      which may be involved in binding the antigen. IgG was able to bind to the
      specific antigen although its conformation was partially modified. Therefore,
      partial modification of the conformation of the antigen-binding site of IgG is
      permissible in order to bind to the antigen.

PMID- 17223787
TI  - DNA-methyltransferase SsoII as a bifunctional protein: features of the
      interaction with the promoter region of SsoII restriction-modification genes.
AB  - DNA duplexes bearing an aldehyde group at the 2'-position of the sugar moiety
      were used for affinity modification of (cytosine-5)-DNA methyltransferase SsoII.
      It is shown that lysine residues of M.SsoII N-terminal region are located in
      proximity to DNA sugar-phosphate backbone of a regulatory sequence of promoter
      region of SsoII restriction-modification enzyme coding genes. The ability of the
      two M.SsoII subunits to interact with DNA regulatory sequence has been
      demonstrated by affinity modification using DNA duplexes with two 2'-aldehyde
      groups. Changes in nucleotide sequence of one half of the regulatory region
      prevented cross-linking of the second M.SsoII subunit. The results on sequential
      affinity modification of M.SsoII by two types of modified DNA ligands (i.e. by 2'
      aldehyde-containing and phosphoryldisulfide-containing) have demonstrated the
      possibility of covalent attachment of the protein to two different DNA
      recognition sites: regulatory sequence and methylation site.

PMID- 17223788
TI  - Complexes of DNA with cationic peptides: conditions of formation and factors
      effecting internalization by mammalian cells.
AB  - This work was devoted to the study of conditions of the formation of DNA/K8
      complex and analysis of factors effecting the entry of DNA/K8 complex into
      mammalian cells in comparison with DNA complexes with arginine-rich fragment (47
      57) of human immunodeficiency virus (type 1) transcription factor Tat (Tat
      peptide). The stoichiometry of positively charged DNA/K8 complexes has been
      studied for the first time. Non-cooperative character of DNA-K8 interaction was
      revealed. It has been shown that along with the positive charge of such
      complexes, the presence of an excess of free K8 peptide in the culture medium is
      a necessary condition for maximal efficiency of cell transfection with DNA/K8
      complexes. A stimulatory effect of free K8 peptide on the efficiency of mammalian
      cell transfection by DNA/K8 complexes is likely to be mediated by the
      interactions of cationic peptide K8 with negatively charged proteoglycans on the
      cell surface, which leads to protection of DNA/K8 complexes from disruption by
      cellular heparan sulfates. However, the protective role of free cationic peptides
      depends not only on their positive charge, but also on the primary structure of
      the peptide. In contrast with the results obtained for DNA complexes with
      molecular conjugates based on poly-L-lysine, the aggregation of DNA/K8 complexes
      leads to a significant increase in the expression of transferred gene.

PMID- 17223789
TI  - Affinity chromatography of GroEL chaperonin based on denatured proteins: role of
      electrostatic interactions in regulation of GroEL affinity for protein
      substrates.
AB  - The chaperonin GroEL of the heat shock protein family from Escherichia coli cells
      can bind various polypeptides lacking rigid tertiary structure and thus prevent
      their nonspecific association and provide for acquisition of native conformation.
      In the present work we studied the interaction of GroEL with six denatured
      proteins (alpha-lactalbumin, ribonuclease A, egg lysozyme in the presence of
      dithiothreitol, pepsin, beta-casein, and apocytochrome c) possessing negative or
      positive total charge at neutral pH values and different in hydrophobicity
      (affinity for a hydrophobic probe ANS). To prevent the influence of nonspecific
      association of non-native proteins on their interaction with GroEL and make
      easier the recording of the complexing, the proteins were covalently attached to
      BrCN-activated Sepharose. At low ionic strength (lower than 60 mM), tight binding
      of the negatively charged denatured proteins with GroEL (which is also negatively
      charged) needed relatively low concentrations (approximately 10 mM) of bivalent
      cations Mg2+ or Ca2+. At the high ionic strength (approximately 600 mM), a tight
      complex was produced also in the absence of bivalent cations. In contrast,
      positively charged denatured proteins tightly interacted with GroEL
      irrespectively of the presence of bivalent cations and ionic strength of the
      solution (from 20 to 600 mM). These features of GroEL interaction with positively
      and negatively charged denatured proteins were confirmed by polarized
      fluorescence (fluorescence anisotropy). The findings suggest that the affinity of
      GroEL for denatured proteins can be determined by the balance of hydrophobic and
      electrostatic interactions.

PMID- 17223790
TI  - Uncoupling effect of lauryl sulfate on mitochondria can be mediated by release of
      bound endogenous fatty acids.
AB  - The mechanism of uncoupling by lauryl sulfate (LS) has been studied. The very
      fact that uncoupling by low concentration of LS (a strong acid) resembles very
      much that by fatty acids (weak acids) was used as an argument against the fatty
      acid cycling scheme of uncoupling where protonated fatty acids operate as a
      protonophore. We have found that rat liver and heart muscle mitochondria can be
      uncoupled by low (70 microM) LS concentration in a fashion completely arrested by
      the ATP/ADP antiporter inhibitor carboxyatractylate (CAtr). On the other hand,
      uncoupling by two-fold higher LS concentration is not sensitive to CAtr. Addition
      of oleate desensitizes mitochondria to low LS so that addition of bovine serum
      albumin becomes necessary to recouple mitochondria. The data are accounted for
      assuming that low LS releases endogenous fatty acids from some mitochondrial
      depots, and these fatty acids are responsible for uncoupling. As to high LS, it
      causes a nonspecific (CAtr-insensitive) damage to the mitochondrial membrane.

PMID- 17223791
TI  - Characterization of catalytic properties of hydrogenase isolated from the
      unicellular cyanobacterium Gloeocapsa alpicola CALU 743.
AB  - The main catalytic properties of the Hox type hydrogenase isolated from the
      Gloeocapsa alpicola cells have been studied. The enzyme effectively catalyzes
      reactions of oxidation and evolution of H2 in the presence of methyl viologen
      (MV) and benzyl viologen (BV). The rates of these reactions in the interaction
      with the physiological electron donor/acceptor NADH/NAD+ are only 3-8% of the
      MV(BV)-dependent values. The enzyme interacts with NADP+ and NADPH, but is more
      specific to NAD+ and NADH. Purification of the hydrogenase was accompanied by
      destruction of its multimeric structure and the loss of ability to interact with
      pyridine nucleotides with retained activity of the hydrogenase component (HoxYH).
      To show the catalytic activity, the enzyme requires reductive activation, which
      occurs in the presence of H2, and NADH accelerates this process. The final
      hydrogenase activity depends on the redox potential of the activation medium
      (E(h)). At pH 7.0, the enzyme activity in the MV-dependent oxidation of H2
      increased with a decrease in E(h) from -350 mV and reached the maximum at E(h) of
      about -390 mV. However, the rate of H2 oxidation in the presence of NAD+ in the
      E(h) range under study was virtually constant and equal to 7-8% of the maximal
      rate of H2 oxidation in the presence of MV.

PMID- 17223792
TI  - Stability of plant mRNAs depends on the length of the 3'-untranslated region.
AB  - Eukaryotic mRNAs that prematurely terminate translation are recognized and
      degraded by nonsense mediated decay (NMD). This degradation pathway is well
      studied in animal and yeast cells. The data available imply that NMD also takes
      place in plants. However, the molecular mechanism of recognition and degradation
      of plant RNAs containing premature terminator codon (PTC) is not known. Here we
      report that in plant cells this mechanism involves the recognition of the sizes
      of the 3'-untranslated regions (3'UTR). Plant 3'UTRs longer than 300 nucleotides
      induce mRNA instability. Contrary to mammalian and yeast cells, this
      destabilization does not depend on the presence of any specific sequences
      downstream of the terminator codon. Unlike nuclear-produced mRNAs, plant virus
      vector long 3'UTR-containing RNAs, which are synthesized directly in the
      cytoplasm, are stable and translated efficiently. This shows that RNAs produced
      in the cytoplasm by viral RNA-dependent RNA polymerase are able to avoid the
      proposed mechanism.

PMID- 17223793
TI  - A genome-wide transcriptional analysis of producer and non-producer NS0 myeloma
      cell lines.
AB  - 'Genome-wide' or 'global' gene expression profiling provides a powerful approach
      to the characterization of a cell's transcriptional state. Such technology has
      been used in animal cell culture to create genome-wide snapshots of
      transcriptional activity in response to environmental factors or cellular
      triggers under bioprocessing conditions. Furthermore, it allows us to have a
      fundamental understanding of genetic mechanisms involved in recombinant protein
      production. One such mechanism adversely affecting the growth of recombinant
      bacteria is the increased metabolic burden resulting from the maintenance of
      plasmid copy number and heterologous protein expression. There have also been
      some reports on the effect of metabolic burden in mammalian cell systems. In the
      present study, we have used a mouse array representing 6400 genes to assess the
      expression profile of a WT (wild-type) mouse plasmacytoma cell line, NS0 WT, and
      a GS (glutamine synthetase)-NS0 6A1-100 cell line expressing chimaeric monoclonal
      antibody. The producer cells did not exhibit a slower growth as the result of any
      metabolic burden, but showed differences in metabolic activity. Gene expression
      profiling revealed that the producer cell line was selected for a higher
      expression of chromosomal genes, genes for zinc-finger proteins as well as cell
      cycle-related events. On the other hand, protein synthesis is greater and
      ribosomal genes were more expressed in the WT cells. A possible shift from
      expressing antigen presenting proteins to recombinant protein could also be seen.
      Hence, gene expression profiling suggests that the effect of the metabolic burden
      in slowing growth can be mostly negated in producer cell lines by careful clonal
      selection, where stable transfected cells are selected for both high productivity
      as well as high growth rates.

PMID- 17223794
TI  - Cotransporters, WNKs and hypertension: important leads from the study of
      monogenetic disorders of blood pressure regulation.
AB  - Major advances are being made in identifying the structure and behaviour of
      regulatory cascades that control the activity of cation-Cl(-) cotransporters and
      certain Na(+), K(+) and Cl(-) channels. These transporters play key roles in
      regulating arterial blood pressure as they are not only responsible for NaCl
      reabsorption in the thick ascending limb and distal tubule of the kidney, but are
      also involved in regulating smooth muscle Ca(2+) levels. It is now apparent that
      defects in these transporters, and particularly in the regulatory cascades, cause
      some monogenetic forms of hypertension and may contribute to essential
      hypertension and problems with K(+) homoeostasis. Two families of kinases are
      prominent in these processes: the Ste-20-related kinases [OSR1 (oxidative stress
      responsive kinase 1) and SPAK (Ste20/SPS1-related proline/alanine-rich kinase)]
      and the WNKs [with no lysine kinases]. These kinases affect the behaviour of
      their targets through both phosphorylation and by acting as scaffolding proteins,
      bringing together regulatory complexes. This review analyses how these kinases
      affect transport by activating or inhibiting individual transporters at the cell
      surface, or by changing the surface density of transporters by altering the rate
      of insertion or removal of transporters from the cell surface, and perhaps
      through controlling the rate of transporter degradation. This new knowledge
      should not only help us target antihypertensive therapy more appropriately, but
      could also provide the basis for developing new therapeutic approaches to
      essential hypertension.

PMID- 17223795
TI  - What's next in translational medicine?
AB  - Translational medicine is the integrated application of innovative pharmacology
      tools, biomarkers, clinical methods, clinical technologies and study designs to
      improve disease understanding, confidence in human drug targets and increase
      confidence in drug candidates, understand the therapeutic index in humans,
      enhance cost-effective decision making in exploratory development and increase
      phase II success. Translational research is one of the most important activities
      of translational medicine as it supports predictions about probable drug
      activities across species and is especially important when compounds with
      unprecedented drug targets are brought to humans for the first time.
      Translational research has the potential to deliver many practical benefits for
      patients and justify the extensive investments placed by the private and public
      sector in biomedical research. Translational research encompasses a complexity of
      scientific, financial, ethical, regulatory, legislative and practical hurdles
      that need to be addressed at several levels to make the process efficient.
      Several have resisted the idea of supporting translational research because of
      its high costs and the fear that it may re-direct funds from other biomedical
      disciplines. Resistance also comes from those more familiar with traditional
      clinical research methods. In this review, we argue that translational research
      should be seen as enabled by ongoing efforts in basic and clinical research and
      not competing with them. Translational research provides the knowledge necessary
      to draw important conclusions from clinical testing regarding disease and the
      viability of novel drug mechanisms. Advancing translational research requires
      education and new sources of funding. This could be achieved through public and
      congressional education by a joint coalition of patients' advocacy groups,
      academia, drug regulatory agencies and industry.

PMID- 17223796
TI  - The mechanism by which molecules containing the HIV gp41 core-binding motif
      HXXNPF inhibit HIV-1 envelope glycoprotein-mediated syncytium formation.
AB  - The HIV-1 gp41 (glycoprotein 41) core plays a critical role in fusion between the
      viral and target cell membranes. We previously identified a gp41 core-binding
      motif, HXXNPF, by screening the phage display peptide libraries. In the present
      study, we elucidated the mechanism of action of HXXNPF motif-containing molecules
      of different sizes, including the phage clone L7.8 (a selected positive phage
      clone), L7.8-g3p* (a 10-kDa fragment of the gene 3 protein) and JCH-4 (a peptide
      containing 13 residues of L7.8-g3p*), regarding their respective binding
      abilities to the six-helix bundle and inhibition on syncytium formation at
      different temperatures. We found that all of the HXXNPF motif-containing
      molecules could bind to the gp41 core, and that their binding sites may be
      located in the N-helix domain. L7.8-g3p* and JCH-4 effectively inhibited HIV-1
      Env (envelope glycoprotein)-mediated syncytium formation at 37 degrees C, while
      the phage clone L7.8 showed no inhibition under the same conditions. However, at
      suboptimal temperature (31.5 degrees C), all of these HXXNPF motif-containing
      molecules were capable of inhibiting syncytium formation. These results suggest
      that these HXXNPF motif-containing molecules mainly bind to the gp41 core and
      stop the fusion process mediated by the fusion-active core, resulting in
      inhibition of HIV-1 fusion and entry. The HXXNPF motif-containing molecules may
      be used as probes for studying the role of the HIV-1 gp41 core in the late stage
      of the membrane-fusion process.

PMID- 17223799
TI  - Fighting for breath: apnoea vs the anaesthetist.

PMID- 17223800
TI  - Evaluation of echocardiography indices of systolic function: a comparative study
      using pressure-volume loops in patients undergoing coronary artery bypass
      surgery.
AB  - Transoesophageal echocardiography measures of systolic left ventricular function
      obtained during coronary artery bypass surgery are heavily influenced by
      alterations in loading conditions. No validation of these measurements against
      load independent indices obtained by pressure-volume loop analysis has been
      undertaken in humans. Ten patients undergoing coronary artery bypass surgery
      underwent simultaneous transoesophageal echocardiography and pressure-volume loop
      analysis of cardiac function at different loading conditions (reduced preload,
      increased afterload and atrial pacing). Fractional area change, afterload
      corrected fractional area change, and lateral basal wall peak systolic myocardial
      velocity, along with dP/dt, were compared to the preload recruitable stroke work
      relationship. There were no significant differences between the echocardiography
      measures when compared to the preload recruitable stroke work relationship;
      however, dP/dt varied significantly across loading conditions (p<0.001).
      Transoesophageal echocardiography adequately assesses systolic function across
      loading conditions commonly seen during coronary artery bypass surgery.

PMID- 17223798
TI  - Role of Ser11 in the stabilization of the structure of Ochrobactrum anthropi
      glutathione transferase.
AB  - GSTs (glutathione transferases) are a multifunctional group of enzymes, widely
      distributed and involved in cellular detoxification processes. In the xenobiotic
      degrading bacterium Ochrobactrum anthropi, GST is overexpressed in the presence
      of toxic concentrations of aromatic compounds such as 4-chlorophenol and
      atrazine. We have determined the crystal structure of the GST from O. anthropi
      (OaGST) in complex with GSH. Like other bacterial GSTs, OaGST belongs to the Beta
      class and shows a similar binding pocket for GSH. However, in contrast with the
      structure of Proteus mirabilis GST, GSH is not covalently bound to Cys10, but is
      present in the thiolate form. In our investigation of the structural basis for
      GSH stabilization, we have identified a conserved network of hydrogen-bond
      interactions, mediated by the presence of a structural water molecule that links
      Ser11 to Glu198. Partial disruption of this network, by mutagenesis of Ser11 to
      alanine, increases the K(m) for GSH 15-fold and decreases the catalytic
      efficiency 4-fold, even though Ser11 is not involved in GSH binding. Thermal- and
      chemical-induced unfolding studies point to a global effect of the mutation on
      the stability of the protein and to a central role of these residues in zippering
      the terminal helix of the C-terminal domain to the starting helix of the N
      terminal domain.

PMID- 17223797
TI  - Pseudomonas aeruginosa and sPLA2 IB stimulate ABCA1-mediated phospholipid efflux
      via ERK-activation of PPARalpha-RXR.
AB  - Bacterial infection triggers an acute inflammatory response that might alter
      phospholipid metabolism. We have investigated the acute-phase response of murine
      lung epithelia to Pseudomonas aeruginosa infection. Ps. aeruginosa triggered
      secretion of the pro-inflammatory lipase, sPLA2 IB (phospholipase A2 IB), from
      lung epithelium. Ps. aeruginosa and sPLA2 IB each stimulated basolateral PtdCho
      (phosphatidylcholine) efflux in lung epithelial cells. Pre-treatment of cells
      with glyburide, an inhibitor of the lipid-export pump, ABCA1 (ATP-binding
      cassette transporter A1), attenuated Ps. aeruginosa and sPLA2 IB stimulation of
      PtdCho efflux. Effects of Ps. aeruginosa and sPLA2 IB were completely abolished
      in human Tangier disease fibroblasts, cells that harbour an ABCA1 genetic defect.
      Ps. aeruginosa and sPLA2 IB induced the heterodimeric receptors, PPARa
      (peroxisome-proliferator-activated receptor-a) and RXR (retinoid X receptor),
      factors known to modulate ABCA1 gene expression. Ps. aeruginosa and sPLA2 IB
      stimulation of PtdCho efflux was blocked with PD98059, a p44/42 kinase inhibitor.
      Transfection with MEK1 (mitogen-activated protein kinase/extracellular-signal
      regulated kinase kinase 1), a kinase upstream of p44/42, increased PPARa and RXR
      expression co-ordinately with increased ABCA1 protein. These results suggest that
      pro-inflammatory effects of Ps. aeruginosa involve release of an sPLA2 of
      epithelial origin that, in part, via distinct signalling molecules,
      transactivates the ABCA1 gene, leading to export of phospholipid.

PMID- 17223801
TI  - Correlation between heart rate variability and haemodynamic fluctuation during
      induction of general anaesthesia: comparison between linear and non-linear
      analysis.
AB  - The objective of this study was to compare linear and non-linear analysis of
      heart rate variability (HRV) in terms of correlation with haemodynamic
      fluctuation during induction of general anaesthesia. Pre-operatively, HRV was
      estimated by the MemCalc method in 114 patients scheduled for general
      anaesthesia. After anaesthesia was induced with propofol, fentanyl and vecuronium
      bromide, tracheal intubation was performed. Haemodynamic fluctuations during
      induction of anaesthesia were recorded and the correlation between pre-operative
      HRV and haemodynamic fluctuation was examined using logistic regression analysis.
      As an index of non-linear analysis of HRV, ultra short-term entropy (UsEn)
      correlated better with blood pressure fluctuation than did the ratio of the power
      of low frequency component of HRV to that of high frequency component (LF/HF). In
      contrast, although LF/HF significantly correlated with heart rate increase caused
      by tracheal intubation, the correlation between UsEn and heart rate fluctuation
      was not significant.

PMID- 17223802
TI  - Anaesthetists' management of oxygen pipeline failure: room for improvement.
AB  - Oxygen pipeline failure is a rare but potentially catastrophic event which can
      affect the care of patients throughout an entire hospital. Anaesthetists play a
      critical role in maintaining patient safety, and should be prepared to support an
      institution-wide emergency response if oxygen failure occurs. We tested the
      preparedness for this through observation of 20 specialist anaesthetists to a
      standardised simulator scenario of central oxygen supply failure. Responses were
      documented using multiple approaches to ensure accuracy. All anaesthetists
      demonstrated safe immediate patient care, but we observed a number of deviations
      from optimal management, including failure to conserve oxygen supplies and,
      following restoration of gas supplies, failure to test the composition of the gas
      supplied from the repaired pipelines. This has implications for patient care at
      both individual and hospital level. Our results indicate a gap in anaesthesia
      training which should be addressed, in conjunction with planning for effective
      hospital-wide responses to the event of critical resource failure.

PMID- 17223803
TI  - Inflation with air via a facepiece for facilitating insertion of a nasogastric
      tube: a prospective, randomised, double-blind study.
AB  - Insertion of a nasogastric tube is a routine procedure but during anaesthesia it
      is often difficult and time consuming. One hundred and sixty adults undergoing
      elective surgery under general anaesthesia were randomly divided into two groups.
      After induction of anaesthesia, neuromuscular blockade and tracheal intubation, a
      nasogastric tube was inserted through the nose with the head of the patient in
      the neutral position, either with or without prior inflation with air via a
      facepiece attached to a self-inflating bag applied firmly with the face.
      Insertion of the nasogastric tube was successful in 75/78 (96%) following
      inflation compared with 54/80 (68%) without inflation (p<0.001). In four patients
      receiving inflation, a fibreoptic endoscope was passed as far as the upper
      oesophageal sphincter; this revealed opening of the upper oesophageal sphincter
      during inflation.

PMID- 17223804
TI  - Tracheal tube tip displacement during laparoscopy in children*.
AB  - The risk of endobronchial intubation during laparoscopy because of displacement
      of the tip of the tracheal tube is a well known problem in adults. Laparoscopy in
      children is increasingly performed, but there are no data available regarding the
      above problem. We prospectively studied 46 children aged 2 months to 15.7 years
      (median 4.2 years) undergoing laparoscopy. After tracheal intubation with the
      Microcuff Pediatric Endotracheal Tube, with the 'intubation depth marking' of the
      tube at the vocal cords, the distance from the tracheal tube tip to the carina
      was endoscopically measured with the patient in the neutral position and with 20
      degrees head-down tilt, both with and without capnoperitoneum. Maximal
      displacement of the tip of the tracheal tube tip in cm was 0.5+(0.05xage (years))
      for 20 degrees head-down tilt, 0.6+(0.09xage (years)) for capnoperitoneum alone,
      and 1.2+(0.11xage (years)) for 20 degrees head-down tilt with capnoperitoneum. In
      no patients did endobronchial intubation occur with the tracheal tube placed
      according to the intubation depth marking.

PMID- 17223805
TI  - A comparison of intubating conditions in children following induction of
      anaesthesia with propofol and suxamethonium or propofol and remifentanil.
AB  - Sixty ASA 1 and 2 children aged between 2 and 16 years who required tracheal
      intubation as part of anaesthesia for elective surgery were studied. We evaluated
      intubating conditions, haemodynamic responses and duration of apnoea following
      propofol 4 mg.kg-1 combined with either remifentanil 1.25 microg.kg-1 (group R),
      or suxamethonium 1 mg.kg-1 (group S). Tracheal intubation was graded as
      excellent, good or poor according to ease of laryngoscopy, vocal cord position,
      coughing, and jaw relaxation and limb movement. Thirty of group S and 28 of group
      R children were successfully intubated on the first attempt. Overall, intubation
      conditions were excellent or good in 26/30 (87%) patients in group S and 20/30
      (67%) in group R (p<0.05). Mean apnoea time was 190 s in group S, and 362 s in
      group R (p<0.001). Heart rate increased in response to suxamethonium (p<0.01) and
      both systolic and diastolic blood pressure decreased in the remifentanil group
      (p<0.01).

PMID- 17223806
TI  - The effect of skin surface warming on pre-operative anxiety in neurosurgery
      patients.
AB  - Skin surface warming of patients not only improves thermal comfort, but has been
      shown to reduce anxiety in a pre-hospital setting. We tested the hypothesis that
      pre-operative warming can reduce pre-operative anxiety as effectively as a
      conventional dose of intravenous midazolam in patients undergoing neurosurgery.
      We randomly allocated 80 patients to four groups in the pre-operative holding
      area. Treatment was applied for 30-45 min with (1) passive insulation and
      placebo; (2) passive insulation and intravenous midazolam (30 microg.kg-1); (3)
      warming with forced-air and placebo; and (4) warming with forced-air and
      intravenous midazolam (30 microg.kg-1). Thermal comfort levels (VAS 0-100 mm) and
      anxiety levels (VAS 0-100 mm, Spielberger State-Trait Anxiety Inventory) were
      assessed twice: before the designated treatment was started and before induction
      of anaesthesia. In the midazolam and the midazolam/warming groups, anxiety VAS
      and Spielberger state anxiety scores decreased by -19 (95% CI: -29 to -9, p<0.01)
      and -10 (95% CI: -14 to -6, p<0.01), respectively. In the warming and the
      combined groups, thermal VAS increased by +26 (95% CI: 17-34, p<0.01). Pre
      operative warming did not reduce anxiety VAS (p=0.11) or Spielberger state
      anxiety (p=0.19). The results of our study indicate that pre-operative warming
      can be recommended solely to improve thermal comfort, not to replace anxiolytic
      premedication regimens.

PMID- 17223808
TI  - Simulators for use in anaesthesia.
AB  - There are many simulators available for use in anaesthetic-related education and
      research. Those who wish to purchase a simulator or to establish a simulation
      facility face a daunting task in understanding the differences between
      simulators. Recent reviews have focused on narrower areas of simulation, such as
      airway management or basic life support, or on the application of simulators. It
      would be difficult to deal in detail with every simulator ever made for
      anaesthesia, but in the present review we cover the spectrum of currently
      available anaesthetic simulators, provide an overview of different types of
      simulator, and discuss a selection of simulators of particular interest,
      including some of historical significance and some examples of 'home made'
      simulators. We have found no common terminology amongst authors for describing or
      classifying simulators, and propose a framework for describing (or classifying)
      them that is simple, clear and applicable to any simulator.

PMID- 17223807
TI  - Mechanisms influencing the vasoactive effects of lidocaine in human skin.
AB  - The vasodilator properties of lidocaine are believed to be due mainly to the
      inhibition of action potentials via sodium channel blocking in vasoconstrictor
      sympathetic nerves. However, mechanisms involving the vascular endothelium may
      also play a role, and in this study we investigated the potential influences of
      nitric oxide release, the cyclo-oxygenase pathway and the beta-adrenoceptors of
      vascular smooth muscle. Laser Doppler imaging was used to measure microvascular
      blood flow responses to intradermal injection of lidocaine 2%, with or without
      the addition of preservatives, in eight healthy, male volunteers. Co-injection of
      the nitric-oxide-synthase inhibitor Nomega-nitro-L-arginine methyl ester caused a
      60% reduction in the response after about 20 min, and this reduction was enhanced
      with the lidocaine solution containing the preservatives methylhydroxybenzoate
      and propylhydroxybenzoate. No reduction in response was seen after blocking the
      cyclo-oxygenase or beta-adrenoceptor pathways. Nitric oxide release contributes
      to the vasoactivity of lidocaine in human skin.

PMID- 17223809
TI  - Minimum and optimum light output of Macintosh size 3 laryngoscopy blades: a
      manikin study.
AB  - Illumination provided by laryngoscope blades varies widely. It is not known what
      the optimum level of illumination should be during laryngoscopy. So far, no
      published standards exist for light intensity provided by laryngoscopes. Fifty
      anaesthetists were recruited to perform laryngoscopy on a manikin with three
      different laryngoscopes attached to a variable voltage supply. Anaesthetists were
      asked to find the minimum and optimum level of light they would wish to have for
      intubation. This study demonstrated that anaesthetists can see the larynx at very
      low light levels. The optimum level was significantly greater than the minimum
      level. The vacuum bulb laryngoscopes provides a significant lower light output
      than halogen and xenon laryngoscopes. There is a large variation in illumination
      requirements amongst anaesthetists which may make setting standards difficult. A
      brighter laryngoscope, as suggested by some manufacturers, may not necessarily be
      a better one.

PMID- 17223810
TI  - Non-conventional uses of the Aintree Intubating Catheter in management of the
      difficult airway.
AB  - We present 14 cases, of which three have been previously reported, in which non
      conventional use was made of the Aintree Intubating Catheter (AIC). In seven
      cases the AIC was used via a ProSeal Laryngeal mask airway (PLMA). Two patients
      had anticipated difficult intubation, two unexpected difficult intubation and two
      required rescue of an obstructed airway prior to AIC-assisted intubation. In two
      cases of tracheal stenosis the AIC was used as a 'long narrow tracheal tube'
      during fibre-optic intubation: the AIC facilitated passage through the narrowed
      trachea and smooth railroading of a tracheal tube. In two cases the AIC was used
      in an awake patient. In three cases the AIC was used successfully despite gross
      laryngeal oedema. In three cases attempted AIC deployment failed: two patients
      had undergone radiotherapy to the mouth and PLMA placement failed; in the third,
      supraglottic oedema prevented visualisation of the larynx. The AIC via an LMA
      Classic was successful in one of these cases. In all cases where the larynx was
      visualised the AIC was rapidly successful without complications. In eight cases
      the anaesthetist had no experience of the technique outside workshops. These
      cases demonstrate general utility of the technique and successful use of the AIC
      via the PLMA, in awake patients, as an adjunct to fibre-optic intubation and in
      patients with an oedematous larynx. Finally, cases where the combination of the
      PLMA and AIC was unsuccessful demonstrate the technique, like many, is not always
      successful.

PMID- 17223811
TI  - Death potentially secondary to sub-Tenon's block.
AB  - An 82-year-old ASA 2 patient underwent routine sub-Tenon's block for cataract
      surgery. One minute after injection of the local anaesthetic, the patient had a
      generalised tonic-clonic seizure and developed refractory ventricular
      fibrillation; subsequent resuscitation was unsuccessful. With no evidence for
      intravascular injection, the lack of structural brain abnormalities, and the most
      striking feature on post mortem examination being severe triple vessel coronary
      artery disease, it was concluded that this was primarily cardiac in origin;
      however, the possibility of brainstem anaesthesia should also be considered.

PMID- 17223812
TI  - Anaesthetic management of uncontrolled idiopathic intracranial hypertension
      during labour and delivery using an intrathecal catheter.
AB  - Idiopathic intracranial hypertension is a rare syndrome characterised by
      prolonged elevation of intracranial pressure in the absence of hydrocephalus,
      intracranial mass lesion or infection, and with increased cerebrospinal fluid
      pressure but a normal composition. We report a case of uncontrolled idiopathic
      intracranial hypertension successfully managed using an intrathecal catheter for
      analgesia in labour and delivery as well as temporary control of intracranial
      pressure.

PMID- 17223813
TI  - Interventional radiological removal of a foreign body from a peripheral bronchus.
AB  - We describe the extraction of an impacted tooth from a bronchiole of a
      ventilated, critically ill patient. Following failed attempts using flexible and
      rigid bronchoscopy a radiological approach was explored. The successful method
      described below used guiding catheters, an extraction basket and an occlusion
      balloon, deployed under fluoroscopic guidance.

PMID- 17223814
TI  - Peri-operative atrioventricular block as a result of chemotherapy with epirubicin
      and paclitaxel.
AB  - A 47-year-old woman presented for mastectomy and immediate latissimus dorsi flap
      reconstruction having been diagnosed with carcinoma of the breast 6 months
      previously. In the preceding months she had received neo-adjuvant chemotherapy
      with epirubicin, paclitaxel (Taxol) and cyclophosphamide. This had been
      apparently uncomplicated and she had maintained a remarkably high level of
      physical activity. She was found to be bradycardic at pre-operative assessment
      but had no cardiac symptoms. Second degree Mobitz type II atrioventricular block
      was diagnosed on electrocardiogram, and temporary transvenous ventricular pacing
      instituted in the peri-operative period. We discuss how evidence-based guidelines
      would not have been helpful in this case, and how chemotherapy can exhibit
      substantial cardiotoxicity that may develop over many years. We suggest that
      patients who have received chemotherapy at any time should have a pre-operative
      electrocardiogram even if they are asymptomatic.

PMID- 17223815
TI  - Training in airway management.

PMID- 17223817
TI  - Breathing system filters for paediatric practice.

PMID- 17223818
TI  - Comparison of the jaw lift with the Berman airway for fibreoptic intubation.

PMID- 17223820
TI  - Risks and benefits of tight glycaemic control.

PMID- 17223822
TI  - Transfer of patients from anaesthetic room to operating theatre.

PMID- 17223823
TI  - Acute peri-operative beta blockade in intermediate-risk patients.

PMID- 17223824
TI  - Transfer of the morbidly obese from anaesthetic room to theatre.

PMID- 17223827
TI  - Routine bacterial culture from epidural catheter tips.

PMID- 17223828
TI  - Maintaining body temperature during surgery.

PMID- 17223830
TI  - Laryngeal oedema complicating extubation.

PMID- 17223829
TI  - Awareness, dreaming or steroid-induced psychosis.

PMID- 17223831
TI  - Airway Scope for difficult intubation.

PMID- 17223832
TI  - Possible malignant hyperthermia during spinal anaesthesia with tetracaine.

PMID- 17223833
TI  - The fiberoptic training jig.

PMID- 17223834
TI  - Intra-operative bradycardia in a patient with Alzheimer's disease treated with
      two cholinesterase inhibitors.

PMID- 17223835
TI  - Prothrombin complex for massive obstetric haemorrhage.

PMID- 17223836
TI  - Airway obstruction from denture fixative.

PMID- 17223837
TI  - Needle-stick injuries from securing central lines.

PMID- 17223839
TI  - A solution to one cause of accidental cuff deflation.

PMID- 17223846
TI  - Optic nerve invasion of uveal melanoma.
AB  - The aim of the study was to identify the histopathological characteristics
      associated with the invasion of the optic nerve of uveal melanoma and to evaluate
      the association between invasion of the optic nerve and survival. In order to
      achieve this, all uveal melanomas with optic nerve invasion in Denmark between
      1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth
      of optic nerve invasion were recorded. The material was compared with a control
      material from the same period consisting of 85 cases randomly drawn from all
      choroidal/ciliary body melanomas without optic nerve invasion. Prelaminar/laminar
      optic nerve invasion was in multivariate analysis associated with focal retinal
      invasion, neovascularization of the chamber angle, and scleral invasion.
      Postlaminar invasion was further associated with non-spindle cell type and
      rupture of the inner limiting membrane of the retina. The optic nerve was invaded
      in four different ways: 1) by tumor extension from the neuroretina through the
      lamina cribrosa; 2) by direct extension into the optic nerve head between Bruch's
      membrane and the border tissue of Elschnig; 3) by direct invasion through the
      border tissue of Elschnig; and 4) in one case a tumor spread along the inner
      limiting membrane to the optic nerve through the lamina cribrosa. Invasion of the
      optic nerve had no impact on all-cause mortality or melanoma-related mortality in
      multivariate analyses. The majority of melanomas invading the optic nerve are
      large juxtapapillary tumors invading the optic nerve because of simple proximity
      to the nerve. A neurotropic subtype invades the optic nerve and retina in a
      diffuse fashion unrelated to tumor size or location.

PMID- 17223838
TI  - Another use for lipid rescue?

PMID- 17223847
TI  - Expression of human telomerase reverse transcriptase and cyclin-D1 in olfactory
      neuroblastoma.
AB  - Olfactory neuroblastoma is an uncommon neoplasm. Typically, these tumors are
      indolent with long-standing symptomatology, but the fact that the lesions are
      indeed malignant has been proven by the repeated demonstration that they can
      metastasize to distant organs. Suitable prognostic factors are lacking and
      therapeutic strategy still remains controversial. Expression of human telomerase
      reverse transcriptase (hTERT) is associated with most human malignancies and high
      levels have been correlated with poor prognosis in many cancers. In comparison,
      overexpression of cyclin-D1 occurs in several malignancies and has been
      associated with aggressive tumor behavior and poorer prognosis. In this study, we
      collected 16 olfactory neuroblastomas from the Kaohsiung Medical University
      Hospital. The aim was to investigate the value of immunoexpression of hTERT and
      cyclin-D1 in correlation with clinicopathologic features of olfactory
      neuroblastoma. Low and high cyclin-D1 expression was found in 6 and 10 cases,
      respectively. For hTERT, low and high protein expression was detected in 5 and 11
      tumors, respectively. Cyclin-D1 expression was not correlated with selected
      parameters. However, high hTERT expression was significantly correlated with high
      Kadish stage. In conclusion, high hTERT expression can be considered a potential
      indicator of aggressive olfactory neuroblastoma.

PMID- 17223848
TI  - The human placenta from heavy smokers: evaluation of vasoactive peptides by
      immunohistochemistry.
AB  - The study aimed to demonstrate the expression of nitric oxide converting enzyme,
      nitric oxide synthase (e-NOS), and endothelin-1 (Et-1) in formalin-fixed paraffin
      embedded placental tissue, and to demonstrate a difference in staining intensity
      between heavy smokers and non-smokers. Term placentas from pregnancies from
      otherwise healthy women smoking 15 or more cigarettes per day (heavy smokers) and
      term placentas from a matching group of non-smokers were included. The antibodies
      for Et-1 and e-NOS are recommended for cryostat sections. We evaluated the
      antibodies on paraffin-embedded tissue combined with the streptavidin-biotin
      peroxidase technique. Et-1 and e-NOS were demonstrated in the placental
      vasculature, the trophoblast, and the amnion. A blinded comparative study showed
      no reproducible significant differences in the staining intensity of the antigen
      antibody reaction to Et-1 and e-NOS between the two groups.

PMID- 17223849
TI  - Different ways to antiangiogenesis by angiostatin and suramin, and quantitation
      of angiostatin-induced antiangiogenesis.
AB  - Angiogenesis, i.e. sprouting of new vessels, their remodelling and regression, is
      a prerequisite for growth and differentiation of organs and tissues. It is
      involved in many pathological processes, particularly growth and metastasis of
      tumours. Angiostatic therapy is a promising new strategy in the treatment of
      cancer. Angiogenesis inhibitors could intervene in the different phases of the
      angiogenic cascade, i.e. migration, proliferation, differentiation and three
      dimensional organisation of endothelial cells, to inhibit the generation of
      tumour vessels. The aim of this study was to explore whether in a previously
      validated in vitro model for quantitation of angiogenesis the effects of the
      angiostatic factors angiostatin and suramin can be investigated and quantified.
      Examination of angiostatin and suramin showed that angiostatin-induced
      antiangiogenesis resulted in inverse angiogenesis. The addition of suramin
      initially resulted in increased angiogenesis. However, long-term incubation
      ultimately led to disintegration of endothelial structures, thus establishing the
      angiostatic effects of suramin. Antiangiogenesis was not only quantified using
      the previously validated method. It also lent itself to assessment of the extent
      of antiangiogenesis within the various phases of the angiogenic cascade. This
      method may therefore be employed in trial studies of potential angiostatic
      substances and related cellular mechanisms.

PMID- 17223850
TI  - Mutational analysis of PTPRT phosphatase domains in common human cancers.
AB  - A recent report revealed that the protein-tyrosine phosphatase, receptor-type, T
      (PTPRT) gene is somatically mutated in several types of human cancer, suggesting
      that the mutated PTPRT gene is a tumor suppressor gene in human cancers. However,
      because previously the mutational search has focused primarily on colon cancers,
      data on PTPRT mutations in other types of human cancer have largely been lacking.
      Here, we performed a mutational analysis of the PTPRT phosphatase domain by
      polymerase chain reaction-based single-strand conformation polymorphism (PCR
      SSCP) assay in 345 cases of common human cancers, including colon carcinomas,
      hepatocellular carcinomas, acute leukemias, gastric carcinomas, breast carcinomas
      and non-small cell lung cancers. We detected PTPRT phosphatase domain mutations
      in 1 of 105 colon carcinomas (1%) and 1 of 48 gastric carcinomas (2%), but none
      in acute leukemias, hepatocellular carcinomas, breast carcinomas and non-small
      cell lung cancers. The PTPRT mutation detected in the colon carcinoma was a
      missense mutation and the mutation in the gastric carcinomas was a splice-site
      mutation. Contrary to the previous report on the frequent PTPTR phosphatase
      domain mutations in colon cancers, this study demonstrated that the somatic
      mutation of the PTPRT phosphatase domain rarely occurred in common human cancers.
      The data suggested that alterations of the PTPRT-mediated signaling pathway by
      PTPRT phosphatase domain mutation may not play a critical role in the development
      of common human cancers.

PMID- 17223851
TI  - Expression pattern of adhesion molecules (E-cadherin, alpha-, beta-, gamma
      catenin and claudin-7), their influence on survival in primary breast carcinoma,
      and their corresponding axillary lymph node metastasis.
AB  - Reduced intercellular adhesion is implicated in the development of metastasis.
      This study investigates the expression of intercellular adhesion molecules (E
      cadherin, alpha-, beta-, gamma-catenin and claudin-7) and their influence on
      survival in primary breast carcinomas and corresponding axillary lymph node
      metastases (ALNM), and evaluates associations between them and with
      clinicopathological factors. The expression of adhesion molecules was analyzed
      immunohistochemically in tissues from 196 patients with primary invasive breast
      carcinomas and their nodal metastases (174 ductal and 22 lobular types). The
      expression was evaluated using semi-quantitative scoring of the intensity and
      proportion of immunoreactivity. All five adhesion proteins showed significantly
      reduced expression in primary ductal carcinomas with re-expression in ALNM
      (p<0.001). In uni- and multivariate analyses, the expression of E-cadherin in the
      primary tumours was a significant predictor of disease-free survival and distant
      disease-free survival. Thus, abnormal E-cadherin expression in the primary
      invasive breast carcinoma seems to be an independent prognostic biomarker in
      predicting a shorter survival in node-positive breast cancer patients. The
      results indicate that abnormal expression of the adhesion molecules in the
      primary tumours with re-expression in corresponding nodal metastases is a common
      event in breast ductal carcinomas and may play a central role in establishing
      metastasis.

PMID- 17223852
TI  - Peripheral neuroblastic tumours in eastern Denmark 1972-2002.
AB  - The peripheral neuroblastic tumour group includes neuroblastoma,
      ganglioneuroblastoma and ganglioneuroma. Neuroblastoma is the most common
      extracranial solid tumour of childhood. We have evaluated the histological
      presentation, MYCN gene status, and clinical course of peripheral neuroblastic
      tumours diagnosed and treated in eastern Denmark from 1972-2002. 125 patients
      were diagnosed with peripheral neuroblastic tumour during this 30-year period.
      The histological material was reviewed and classified into three categories in
      accordance with the Shimada system: unfavourable histology, favourable histology,
      and benign tumours. MYCN status was determined by fluorescent in situ
      hybridization (FISH) on paraffin sections from the primary tumour. Clinical
      information was obtained from hospital records. Diagnostic likelihood ratios in
      the two groups were calculated to compare the ability of MYCN status and
      histological classification to predict 5-year outcome. 41 tumours showed
      unfavourable histology, 30 tumours showed favourable histology, 11 were benign,
      and 43 were unclassifiable due to limited amounts of primary tumour, bad
      preservation or inaccessibility of the primary tumour necessitating metastatic
      tumour biopsy for diagnosis. Unfavourable histology was associated with
      widespread disease (p<0.001). The overall 5-year survival rate was 45%, which
      correlates well with the European survival rate reported for this time period.
      The 5-year survival rate in the unfavourable group was 30% as compared to 100% in
      the favourable histology group (p<0.001). The survival rate in the unclassifiable
      group was 13%. 26% of the neuroblastomas were MYCN amplified. MYCN amplification
      was associated with undifferentiated histology, a histological subtype of the
      unfavourable histology group (p<0.001). For unfavourable histology the positive
      diagnostic likelihood ratio was 2.9 as compared to 4.7 for MYCN amplification.
      The study has confirmed the prognostic significance of the Shimada system in the
      peripheral neuroblastic tumour group in a retrospective material, and has also
      demonstrated the prognostic superiority of MYCN compared to histological
      classification, thus reducing the necessary amounts of tumour tissue.

PMID- 17223853
TI  - Congenital cervical immature teratoma arising in the left lobe of the thyroid
      gland.
AB  - We report on a fetal autopsy case in which a congenital cervical immature
      teratoma was diagnosed. A 24-year-old Japanese woman had carried a male fetus
      that was aborted because of a cervical tumor at 20 weeks 5 days of gestation. The
      cervical tumor weighed 93 g and measured 7.5x5.5x5 cm. The soft tumor was
      encapsulated by a fibrous layer, was solid with small cysts on the cut surface,
      and showed a brain-like appearance. The tumor was composed of neoplastic cells
      derived from the three germ cell layers: ectoderm, mesoderm, and endoderm. The
      cells showed both immature and mature features. Small areas of thyroid tissue
      were detected in the cervical tumor. The left lobe of the thyroid gland was not
      observed, but the right lobe of the thyroid gland was present laterally between
      the trachea and the esophagus. Therefore, we concluded that the cervical tumor
      had arisen in the left lobe of the thyroid gland rather than from the soft tissue
      of the neck.

PMID- 17223854
TI  - Sustained activation of extracellular signal-regulated kinase by nerve growth
      factor regulates c-fos protein stabilization and transactivation in PC12 cells.
AB  - The duration of intracellular signaling is thought to be a critical component in
      effecting specific biological responses. This paradigm is demonstrated by growth
      factor activation of the extracellular signal-regulated kinase (ERK) signaling
      cascade in the rat pheochromocytoma cell line (PC12 cells). In this model,
      sustained ERK activation induced by nerve growth factor (NGF) results in
      differentiation, whereas transient ERK activation induced by epidermal growth
      factor (EGF) results in proliferation in these cells. Recently, the immediate
      early gene product c-fos has been proposed to be a sensor for ERK signaling
      duration in fibroblasts. In this study, we ask whether this is true for NGF and
      EGF stimulation of PC12 cells. We show that NGF, but not EGF, can regulate both c
      fos stability and activation in an ERK-dependent manner in PC12 cells. This is
      achieved through ERK-dependent phosphorylation of c-fos. Interestingly, distinct
      sites regulate enhanced stability and transactivation of c-fos. Phosphorylation
      of Thr325 and Thr331 are required for maximal NGF-dependent transactivation of c
      fos. In addition, a consensus ERK binding site (DEF domain) is also required for
      c-fos transactivation. However, stability is controlled by ERK-dependent
      phosphorylation of Ser374, while phosphorylation of Ser362 can induce
      conformational changes in protein structure. We also provide evidence that
      sustained ERK activation is required for proper post-translational regulation of
      c-fos following NGF treatment of PC12 cells. Because these ERK-dependent
      phosphorylations are required for proper c-fos function, and occur sequentially,
      we propose that c-fos is a sensor for ERK signaling duration in the neuronal-like
      cell line PC12.

PMID- 17223855
TI  - Effects of clarithromycin and grapefruit juice on the pharmacokinetics of
      glibenclamide.
AB  - AIMS: Case reports suggest that clarithromycin can increase the glucose-lowering
      effect of glibenclamide which is metabolized mainly by CYP2C9 and is a substrate
      for P-glycoprotein and OATP2B1. Our objective was to evaluate whether the P
      glycoprotein inhibitor, clarithromycin, increases and the putative OATP2B1
      inhibitor, grapefruit juice, decreases plasma concentrations of glibenclamide.
      METHODS: In a randomized three-phase crossover study, 12 subjects ingested 250 mg
      clarithromycin or placebo twice daily or 200 ml grapefruit juice three times
      daily for 2 days. On day 3, they ingested 0.875 mg glibenclamide with sugar water
      or grapefruit juice. Concentrations of glibenclamide and clarithromycin in
      plasma, glucose in blood, and excretion of hydroxy-glibenclamide into urine were
      measured up to 12 h. RESULTS: Clarithromycin increased the peak concentration
      (C(max)) of glibenclamide to 1.25-fold (95% confidence interval (CI) 1.12, 1.40;
      P < 0.01) and the area under the plasma concentration-time curve to 1.35-fold
      (95% CI 1.21, 1.50; P < 0.01) compared with the placebo phase. The time to
      C(max), the half-life of glibenclamide, and the amount of hydroxy-glibenclamide
      excreted into urine remained unaltered. Grapefruit juice did not change the
      pharmacokinetics of glibenclamide. Clarithromycin concentrations implied a good
      compliance. Blood glucose did not deviate between the phases. CONCLUSIONS:
      Clarithromycin increased plasma concentrations of glibenclamide, possibly by
      inhibiting P-glycoprotein in the intestinal wall. Although not seen with the
      present study design, clarithromycin may enhance the effect of glibenclamide by
      increasing plasma glibenclamide concentrations, which warrants close monitoring
      of blood glucose during their co-administration. Grapefruit juice had no effect
      on glibenclamide pharmacokinetics.

PMID- 17223857
TI  - The pharmacokinetics, CNS pharmacodynamics and adverse event profile of
      brivaracetam after single increasing oral doses in healthy males.
AB  - AIMS: The objective of the study was to evaluate the pharmacokinetics (and how
      they are affected by food), CNS pharmacodynamics and the adverse event profile of
      brivaracetam after single increasing doses. METHODS: Healthy males (n = 27,
      divided into three alternating panels of nine subjects) received two different
      single oral doses of brivaracetam (10-1400 mg) and one dose of placebo during
      three periods of a randomized, double-blind, placebo-controlled study. The effect
      of food on its pharmacokinetics was assessed using a standard two-way crossover
      design in a further eight subjects who received two single oral doses of
      brivaracetam (150 mg) in the fasting state and after a high fat meal. RESULTS:
      Adverse events, none of which were serious, were mostly CNS-related and included
      somnolence, dizziness, and decreased attention, alertness, and motor control.
      Their incidence, severity and duration were dose-related. The maximum tolerated
      dose was established to be 1000 mg. Severe somnolence lasting 1 day occurred in
      one subject following 1400 mg. Brivaracetam was rapidly absorbed under fasting
      conditions, with a median t(max) of approximately 1 h. C(max) was dose
      proportional from 10 to 1400 mg, whereas AUC deviated from dose linearity above
      600 mg. A high-fat meal had no effect on AUC (point estimate 0.99, 90%CI: 0.92
      1.07) but delayed t(max) (3 h) and decreased C(max) (point estimate 0.72, 90%CI:
      0.66-0.79). CONCLUSIONS: Brivaracetam was well tolerated after increasing single
      doses that represent up to several times the expected therapeutic dose.
      Brivaracetam was found to have desirable pharmacokinetic properties. The most
      common adverse events were somnolence and dizziness.

PMID- 17223856
TI  - Variability in non-nucleoside reverse transcriptase and protease inhibitors
      concentrations among HIV-infected adults in routine clinical practice.
AB  - AIMS: The objective of this study was to assess interindividual variability in
      plasma trough concentrations of non-nucleoside reverse transcriptase inhibitors
      (NNRTI) and protease inhibitors (PI) among HIV-infected adults in an outpatient
      routine clinical practice setting. METHODS: The study included 117 patients who
      attended our clinic for routine outpatient blood tests and who were receiving
      antiretroviral therapy which included NNRTI or PI. Patients were not informed
      that drug concentrations were going to be assessed until blood sampling. The time
      of the last antiretroviral treatment intake and blood sampling were recorded.
      Drug concentrations were considered optimal if they were above the proposed
      minimum effective concentration. In addition, efavirenz, nevirapine and
      atazanavir concentrations were considered potentially toxic if they were higher
      than 4.0 mg l(-1), 6.0 mg l(-1), and 0.85 mg l(-1), respectively. RESULTS:
      Overall, interindividual variability in NNRTI and PI plasma concentrations was
      approximately 50%, and only 68.4% of the patients had drug concentrations within
      the proposed therapeutic range. Inappropriate adherence only explained 35% of
      subtherapeutic drug concentrations. CONCLUSION: Interindividual variability in
      trough concentrations of NNRTI and PI among HIV-infected adults is large in
      routine clinical practice, with drug concentrations being outside the therapeutic
      window in a significant proportion of patients. Therapeutic drug monitoring may
      be useful to guide antiretroviral therapy in clinical practice.

PMID- 17223858
TI  - Protein binding of cefazolin is saturable in vivo both between and within
      patients.
AB  - AIMS: The aims of the study were a) to determine if there is evidence of
      saturable protein binding of cefazolin in plasma across the range of
      concentrations achieved clinically (between patient variability) and b) to
      investigate whether saturable protein binding is also evident from trough and
      peak concentrations in the same patient (within patient variability). METHODS:
      Unbound and total plasma concentrations were measured in patients who were
      treated with cefazolin intravenously by continuous infusion or intermittent
      injection. In study (i) single random samples were taken from one series of
      patients. In study (ii) paired samples (troughs and peaks) were taken from a
      second series of patients. RESULTS: Thirty-one patients were included in study
      (i). Linear regression analysis of the percentage unbound vs. unbound plasma
      concentrations revealed a slope significantly different from zero, suggesting
      saturable protein binding. Mean values for percentage unbound ranged from 9% at
      low concentrations (8.5 mg l(-1)) to 51% at high concentrations (140 mg l(-1)).
      Twelve patients were investigated in study (ii). Values for protein binding
      ranged from 85% at low concentrations (2.7 mg l(-1)) to 52% at high
      concentrations (200.3 mg l(-1)). The percentage unbound was significantly higher
      (P < 0.0001) at high (peak) concentrations than at lower (trough) concentrations,
      confirming saturable protein binding. CONCLUSIONS: The protein binding of
      cefazolin is saturable in vivo in humans, both between and within patients.

PMID- 17223859
TI  - A systematic review of the safety of topical therapies for atopic dermatitis.
AB  - BACKGROUND: The safety of topical therapies for atopic dermatitis (AD), a common
      and morbid disease, has recently been the focus of increased scrutiny, adding
      confusion as how best to manage these patients. OBJECTIVES: The objective of
      these systematic reviews was to determine the safety of topical therapies for AD.
      METHODS: Databases searched included: OVID Medline, Medline In-Process and Other
      Non-Indexed Citations, Embase, and the Cochrane Central Register of Controlled
      Trials. In addition to the articles identified by this search, investigators were
      also referred to a list of links (most recently updated 25 September 2005) to
      recent Food and Drug Administration (FDA) studies, reports and meetings regarding
      the topical calcineurin inhibitors for further potential references. Only fully
      published papers available in English and data obtained from FDA sites were
      included. Furthermore, the criteria for inclusion and exclusion for each
      systematic review were further evaluated at a meeting of all of the content and
      evidence-based medicine experts participating in this process and alteration of
      the inclusion criteria was done at that time when it was felt necessary to avoid
      inclusion of lower-quality data in the review. Qualitative review of the
      abstracted data was performed and reviewed at a meeting of all of the content and
      evidence-based medicine experts. RESULTS: While systemic exposure to these
      topical agents does occur, physiological changes appear to be uncommon and
      systemic complications rare and have only been found with use of topical
      corticosteroids. CONCLUSIONS: Based on the data that are available the overall
      safety of AD therapies appears to be good with the only documented systemic side
      effects of therapy those occasionally seen with use of topical corticosteroids.

PMID- 17223860
TI  - Guidelines for the management of actinic keratoses.
AB  - These guidelines stemmed from a consensus meeting held by the British
      Photobiology Group (BPG) in 1999. Following this meeting one of the authors
      (J.M.M.) was invited to draw up guidelines for the management of actinic
      keratoses by the British Association of Dermatologists Therapy Guidelines and
      Audit Subcommittee. Relevant evidence was sought using the search terms 'solar
      keratosis' and 'actinic keratosis' in Medline from 1966 onwards. Additional and
      earlier literature was reviewed on the basis of references within post-1966
      publications. All articles of apparent relevance were reviewed independently of
      the nature of the publication. The quality of the evidence elicited has been
      indicated. The National Ambulatory Medical Care Survey (U.S.A.) was used for
      further data on topical chemotherapy. Papers were reviewed and discussed by the
      contributors to the BPG Workshop (see Acknowledgments). Recommendations are
      evidence based where possible. Strength of recommendation is coupled with quality
      of evidence. Strength of recommendation includes consideration of apparent cost
      benefit and practical considerations. Quality of evidence reflects the nature of
      the trial structure that provides data of efficacy.

PMID- 17223861
TI  - Acute barrier disruption by adhesive tapes is influenced by pressure, time and
      anatomical location: integrity and cohesion assessed by sequential tape
      stripping. A randomized, controlled study.
AB  - BACKGROUND: Tape stripping is an established procedure in stratum corneum (SC)
      physiology research. Adhesive films are pressed to the surface of the skin and
      then removed. The superficial layers of the SC adhere to the film and are
      accessible for further investigations. Although this method is widely used, only
      scant information about standardization is known. Various protocols are used but
      are difficult to compare. OBJECTIVES: The aim of the present study was to
      investigate the effects of the type of tape, pressure, time, anatomical site and
      type of applied pressure. METHODS: Twelve healthy volunteers (age range 20-31
      years) were entered in a randomized, controlled study with sequential tape
      stripping at the volar forearm, upper arm, cheek and back. Different methods
      (roller, stamp, thumb, stretched skin), total duration of applied pressure (2 s,
      10 s), degrees of pressure (2 N stamp, 7 N stamp) and different tapes (D-Squame,
      Corneofix, Blenderm) were investigated and the impact on barrier function
      assessed by transepidermal water loss measurements. Furthermore, measurements of
      SC hydration, skin colour and skin surface pH were performed. Spectroscopic
      measurements and a Bradford protein assay to determine the mass of removed SC
      were carried out in parallel. RESULTS: The degree of barrier disruption,
      irritation and SC cohesion is influenced by the character of adhesive tapes,
      total duration of applied pressure (2 s, 10 s; 2 N, 7 N), the kind of method for
      pressure application (roller, stamp, thumb, stretched skin), anatomical site and
      condition before stripping (occlusion vs. nonocclusion). The spectroscopic
      assessment and Bradford protein assay determination showed a significant
      correlation (P < 0.0001; r = 0.7041). CONCLUSIONS: The present study showed
      significant differences between different factors on controlled barrier
      disruption. The results indicate the importance of defining these factors when a
      study is initiated and when results of different studies should be compared.
      Based on our data we propose using a 2 N stamp for a duration of 2 s on 15
      sequential D-Squame tape strips on the volar forearm and then discarding the
      first and second strips. This approach allows the performance of a standardized
      study with a reasonable amount of resources.

PMID- 17223862
TI  - Effects of high-affinity nerve growth factor receptor inhibitors on symptoms in
      the NC/Nga mouse atopic dermatitis model.
AB  - BACKGROUND: Nerve growth factor (NGF) is an important substance in the skin,
      where it modulates nerve maintenance and repair. However, the direct link between
      NGF and pruritic diseases such as atopic dermatitis is not yet fully understood.
      Our previous study showed that NGF plays an important role in the pathogenesis of
      atopic dermatitis-like skin lesions in NC/Nga mice. NGF mediates its effects by
      binding to two classes of transmembrane receptors, a high-affinity receptor
      (tropomyosin-related kinase A, TrkA) and a low-affinity receptor (p75).
      OBJECTIVES: To determine the significance of NGF receptors in the pathogenesis of
      atopic dermatitis, the effects of TrkA inhibitors AG879 and K252a on the symptoms
      of NC/Nga mice were evaluated. METHODS: Male NC/Nga mice with severe skin lesions
      were used. AG879 or K252a was applied to the rostral part of the back of mice
      five times a week. The dermatitis score for the rostral back was assessed once a
      week. The scratching behaviour was measured using an apparatus, MicroAct
      (Neuroscience, Tokyo, Japan). Immunofluorescence examinations were made in the
      rostral back skin for nerve fibres, NGF and TrkA receptor. RESULTS: Repeated
      applications of AG879 or K252a significantly improved the established dermatitis
      and scratching behaviour, and decreased nerve fibres in the epidermis. NGF was
      observed more weakly in keratinocytes, and a lower expression of TrkA was
      observed in stratum germinativum of the epidermis of mice treated with AG879 or
      K252a compared with those treated with vehicle. CONCLUSIONS: We suggest that NGF
      plays an important role in the pathogenesis of atopic dermatitis-like skin
      lesions via the high-affinity NGF receptor. These findings provide a new
      potential therapeutic approach for the amelioration of symptoms of atopic
      dermatitis.

PMID- 17223863
TI  - Transglutaminase inhibitors induce hyperproliferation and parakeratosis in tissue
      engineered skin.
AB  - BACKGROUND: The transglutaminase (TG) family consists of eight distinct isoforms.
      TG types 1, 3 and 5 play a major role in normal skin development, with TG2 also
      being elevated during dermal wounding. TG1, 3 and 5 are responsible for the cross
      linking of keratin precursors and formation of the cornified envelope during
      keratinocyte differentiation. TG2 may play a role in keratinocyte basement
      membrane cross-linking. Abnormal TG expression has been demonstrated in Darier
      disease, Netherton syndrome, psoriasis and lamellar ichthyosis. During a recent
      investigation of skin contraction in tissue-engineered skin, transglutaminase
      inhibitors were found to produce hyperproliferation and parakeratosis.
      OBJECTIVES: Accordingly, this study was designed to study the effect of pan
      transglutaminase inhibition on morphology of tissue-engineered skin and
      expression of keratinocyte differentiation and proliferation-associated antigens.
      METHODS: We used a tissue-engineered model of human skin, based on de-epidermized
      acellular human dermis, seeded with normal keratinocytes and dermal fibroblasts
      and cultured at an air-liquid interface. The pan-transglutaminase inhibitors
      putrescine, NTU283 (1-dimethyl,2-[(oxopropyl)thio]imidazolium) and NTU285 (N
      benzyloxycarbonyl-l-glutaminyl-6-dimethylsulfonium-5-oxo-l-norleucine) were added
      to the culture medium. After 28 days, histology and immunohistochemistry for
      collagen IV, involucrin and cytokeratins 6, 10 and 16 were performed. RESULTS:
      Keratinocyte hyperproliferation and parakeratosis were seen in response to
      transglutaminase inhibition. Inhibition of transglutaminase also resulted in loss
      of basement membrane collagen IV. Involucrin and cytokeratins 6 and 16 were
      confined to the basal layers in control composites but expressed throughout the
      epidermis in response to transglutaminase inhibition. A distinct band of
      expression of cytokeratin 10 was seen in the upper stratum granulosum of control
      composites but only patchy expression was seen after transglutaminase expression.
      CONCLUSIONS: Pan-transglutaminase inhibition inhibits terminal differentiation of
      keratinocytes, leading to a hyperproliferative epidermis with parakeratosis and
      enhanced expression of involucrin and cytokeratins 6 and 16. Expression of the
      differentiation-associated cytokeratin, cytokeratin 10, is reduced. Basement
      membrane integrity is also lost as a result of transglutaminase inhibition.

PMID- 17223864
TI  - A classification of psoriasis vulgaris according to phenotype.
AB  - For nearly 200 years it has been appreciated that plaque psoriasis consists of a
      number of distinct clinical phenotypes. However, a reliable and simple
      stratification of clinical presentation of psoriasis is lacking. In the era of
      immunogenetic association studies and an advanced understanding of the
      pathomechanisms of psoriasis it is important that a classification of the disease
      according to phenotype is readily available. Such a classification would
      facilitate clinically relevant interpretation of investigational data. A meeting
      of the International Psoriasis Council produced a consensus on clinical
      phenotypes of psoriasis equally relevant to clinical practitioners and psoriasis
      researchers.

PMID- 17223865
TI  - Oral retinoic acid metabolism blocking agent Rambazole for plaque psoriasis: an
      immunohistochemical study.
AB  - BACKGROUND: The novel systemic all-trans retinoic acid metabolism blocking agent
      (RAMBA) R115866 (Rambazole(TM); Barrier Therapeutics, Geel, Belgium; further
      referred to as rambazole) increases intracellular levels of endogenous all-trans
      retinoic acid (RA). Well-known effects of RA are normalization of aberrant
      epithelial growth and differentiation. Hence, rambazole might be beneficial in
      the treatment of plaque psoriasis. OBJECTIVES: The dynamics of epidermal
      proliferation, keratinization, lesional T-cell subsets and cells expressing
      natural killer (NK)-receptors in plaque psoriasis were assessed during treatment
      with rambazole, as part of a phase IIa open-label clinical trial. METHODS: Six
      patients were treated with rambazole, 1 mg, once daily, for 8 weeks. At weeks 0,
      2 and 8, psoriatic plaque severity scores (SUM) and biopsies from a target lesion
      were assessed. Epidermal proliferation (Ki67), keratinization markers (K10, K13,
      K19), T-cell subsets (CD3, CD4+, CD8+, CD45RO+, CD45RA+, CD2+, CD25+, GITR+) and
      cells expressing NK-receptors (CD94, CD161) were immunohistochemically stained
      and quantified with image analysis. RESULTS: At week 2 the mean SUM-score was
      virtually equal to baseline, which was accompanied immunohistochemically by equal
      epidermal hyperproliferation, a nonsignificant decrease in K10 positive epidermis
      and, overall, a nonsignificant increase in immunocyte subsets. At week 8, in
      contrast, plaque severity was reduced by 34% from baseline (P < 0.05).
      Improvements were also detected for epidermal proliferation (-63%; P < 0.01) and
      K10 expression (+29%; P < 0.01), compared with baseline. No induction of retinoid
      specific keratinization (K13, K19) was observed. A nonsignificant reduction of
      all pathogenic T-cell subsets and cells expressing NK-receptors was observed at
      week 8 of treatment (P > 0.05). CONCLUSIONS: Clinical efficacy of rambazole is
      primarily the result of restoring proliferation (Ki67) and differentiation (K10)
      of epidermal keratinocytes. Secondly, relevant T-cell subsets and cells
      expressing NK-receptors showed nonsignificant reductions after 8 weeks of
      treatment with rambazole.

PMID- 17223866
TI  - Psoriasis: a possible risk factor for development of coronary artery
      calcification.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disorder affecting about 2%
      of white-skinned individuals. Epidemiological data on the prevalence and degree
      of coronary artery calcification (CAC) as an indicator for cardiovascular
      diseases in patients with psoriasis are contradictory. OBJECTIVES: To study the
      prevalence and degree of CAC as an indicator for cardiovascular diseases in 32
      patients with psoriasis matched for age, sex and risk factors to an equally sized
      control population. METHODS: Noncontrast-enhanced 16-row spiral computed
      tomography was performed in patients and controls. RESULTS: We found a
      significantly increased prevalence (59.4% vs. 28.1%, P = 0.015) and severity (CAC
      score according to Agatston 3.7 vs. 0.0, P = 0.019) of CAC in patients with
      psoriasis. Multiple linear regression calculations identified psoriasis as a
      likely independent risk factor for CAC. CONCLUSIONS: Our results point towards
      the potentially systemic nature of the inflammatory processes underlying the
      pathogenesis of psoriasis, which may therefore be considered a potentially severe
      systemic disease.

PMID- 17223867
TI  - Association between cutaneous melanoma, Breslow thickness and vitamin D receptor
      BsmI polymorphism.
AB  - BACKGROUND: Literature data report an association between some vitamin D receptor
      (VDR) polymorphisms and different kinds of tumours, including malignant melanoma
      (MM). Only three VDR polymorphisms (FokI, TaqI and A-1012G) have been
      investigated in association with the presence of cutaneous MM or the development
      of metastases. OBJECTIVES: The present paper analyses for the first time the
      association between BsmI polymorphism and MM prevalence together with Breslow
      thickness. In addition, the FokI single nucleotide polymorphism was also
      determined. METHODS: One hundred and one patients with MM and 101 healthy donors
      matched for age and sex were enrolled. Molecular VDR typing was performed by
      means of restriction fragment length polymorphism analysis. RESULTS: All cases
      and controls were in Hardy-Weinberg equilibrium for BsmI, FokI and A-1012G.
      Significant associations were found between the BsmI bb genotype frequency and MM
      (P = 0.02) along with Breslow thickness (P = 0.001). This same behaviour was not
      observed for the FokI or A-1012G polymorphisms. Multivariate logistic regression
      analysis confirmed these significant results after correction for age, gender,
      skin type and MM localization. CONCLUSIONS: Although the biological meaning of
      the effects exerted by BsmI polymorphism is still under debate, the statistical
      association found in the present study suggests that further work should be done
      to verify this variant as a possible risk marker for MM and its aggressiveness,
      also considering that the real association may be due to other unknown genes
      linked to the BsmI b allele.

PMID- 17223868
TI  - Atopic dermatitis in adolescent boys is associated with greater psychological
      morbidity compared with girls of the same age: the Young-HUNT study.
AB  - BACKGROUND: Having atopic dermatitis (AD) as well as other chronic diseases is
      often associated with reduced mental health. Adolescents with AD are thought to
      be especially vulnerable, but few studies have included an ample number of young
      people. OBJECTIVES: To study self-reported mental distress among boys and girls
      13-19 years of age with AD compared with mental distress among healthy
      adolescents as well as mental distress among adolescents with other chronic
      diseases or complaints, such as headache, neck or shoulder pain, asthma, allergy
      and rhinitis. METHODS: The Young-HUNT study was conducted as a cross-sectional,
      population-based survey in 1995-97. All students in Nord-Trondelag County,
      Norway, aged 13-19 years were invited, and some 89% participated. A questionnaire
      on mental and somatic health, life-style and social conditions was completed
      during one school hour. RESULTS: A total of 4384 girls and 4433 boys
      participated. The prevalence of mental distress was higher among older teenagers,
      and more than every fourth girl aged 17-19 reported mental distress. Although
      more girls than boys reported mental distress, AD, headache and neck or shoulder
      pain, the odds for reporting both AD and mental distress were higher for boys
      [odds ratio (OR) = 2.1 (1.6-2.9)] compared with girls [OR = 1.3 (1.1-1.6)]. A
      corresponding sex difference in reporting mental distress was also seen for some
      other chronic diseases or complaints. CONCLUSIONS: In adolescents aged 13-19
      years there was a strong and significant association between self-reported mental
      distress and AD as well as headache and neck or shoulder pain for both sexes.
      Although boys reported fewer complaints as AD, they perceived the complaints a
      heavier burden than did the girls.

PMID- 17223869
TI  - Genomic-scale analysis of psoriatic skin reveals differentially expressed insulin
      like growth factor-binding protein-7 after phototherapy.
AB  - BACKGROUND: Phototherapy is an effective therapy for psoriasis. The molecular
      mechanisms underlying its efficacy are not yet understood. OBJECTIVES: To compare
      the expression profiles of psoriatic epidermis in patients before and after
      undergoing phototherapy with the purpose of expounding the molecular mechanisms
      underlying the efficacy of this therapeutic modality. METHODS: Patients with
      psoriasis were investigated before and after full courses of phototherapy: three
      patients completed 3 weeks of heliotherapy at the Dead Sea; three patients
      received narrowband ultraviolet B (NB-UVB) for a total of 20-27 treatments.
      Epidermal samples were analysed using oligonucleotide microarrays. Our microarray
      results led us to explore further and to quantify a specific gene, insulin-like
      growth factor-binding protein-7 (IGFBP7), using real-time quantitative reverse
      transcriptase-polymerase chain reaction assays and immunohistochemical protein
      expression. RESULTS: We identified 315 genes modulated by phototherapy: the
      expressions of 248 genes (142 up; 106 down) were changed by Dead Sea treatment,
      116 (71 up; 45 down) by NB-UVB and 49 (37 up; 12 down) were modulated regardless
      of treatment. The differentially changed genes include S100 calcium-binding
      proteins, dendritic cell markers, tumour necrosis factor-alpha target genes,
      matrix metalloproteinases and NFkappaB target genes. We also found that IGFBP7
      mRNA and protein were significantly underexpressed in psoriatic compared with
      normal epidermis, and that phototherapy significantly increased their expression.
      CONCLUSIONS: IGFBP7 is underexpressed in psoriatic epidermis but is inducible by
      UVB.

PMID- 17223870
TI  - Phototoxic reaction and porphyrin fluorescence in skin after topical application
      of methyl aminolaevulinate.
AB  - BACKGROUND: Photodynamic therapy using topical methyl aminolaevulinate (MAL) is a
      new treatment modality for skin disorders. MAL is metabolized into endogenous
      porphyrins, which act as photosensitizers when illuminated. OBJECTIVES: To
      evaluate the severity and duration of skin photosensitivity after MAL
      application, and to investigate its relation to the presence of endogenous
      porphyrins. METHODS: Placebo and 160 mg g(-1) MAL creams were randomly assigned
      to contralateral sites located at the forearms and fingertips of 16 healthy
      volunteers and were applied for 3 h. The porphyrin content in the skin was
      monitored by in situ fluorescence measurements following cream removal.
      Phototoxic reaction was evaluated after exposure to a high dose of red light.
      RESULTS: The porphyrin fluorescence in forearm skin peaked about 1 h after the
      cream removal, was halved after 8 h, and was reduced by > 90% within 24 h. Most
      forearm sites were photosensitive at 1 and 8 h following cream removal. Six
      subjects were still sensitive at 24 h, and at this time point the phototoxicity
      was coincidental with residual porphyrin fluorescence. In general, all reactions
      were mild or moderate, and included pain, erythema, oedema and transient
      hyperpigmentation. No photosensitivity or porphyrin fluorescence was detected at
      48 h. At the fingertips photosensitivity was absent except for sporadic cases of
      mild pain. CONCLUSIONS: Topical MAL application and exposure to red light induced
      mild and moderate phototoxicity. The photosensitivity ceased within 24-48 h after
      cream removal, and its duration was associated with the degradation of
      porphyrins.

PMID- 17223871
TI  - Treatment of actinomycetoma due to Nocardia spp. with amoxicillin-clavulanate.
AB  - BACKGROUND: Actinomycetoma is a chronic occupational condition that occurs
      frequently in tropical regions. In Mexico 85% of cases are caused by Nocardia
      brasiliensis. There are two treatments of choice for these cases: a regimen of
      dapsone plus trimethoprim-sulfamethoxazole (co-trimoxazole) and, recently,
      amikacin, either alone or combined. However, not all cases respond properly to
      these therapies. OBJECTIVES: To report a retrospective, 11-year study of cases of
      actinomycetomas caused by Nocardia spp., treated with amoxicillin-clavulanate (co
      amoxiclav). METHODS: All cases were identified clinically and microbiologically
      and had previously failed standard therapies. Oral co-amoxiclav 875/125 mg was
      administered every 12 h. Clinical, microbiological and laboratory follow up was
      performed every 2 months during the treatment period. RESULTS: Twenty-one cases
      of actinomycetoma were included, 19 caused by N. brasiliensis and one each by N.
      asteroides and N. otitidiscaviarum. Clinical and microbiological cure occurred in
      15 of 21 cases (71%); two cases improved (10%) and four failed (19%). Mean
      treatment period was 9.6 months, during which neither side-effects nor laboratory
      test alterations were reported. CONCLUSIONS: Treatment with co-amoxiclav
      represents an alternative or rescue treatment for cases that have previously
      failed standard therapies.

PMID- 17223872
TI  - The comparative effects of tacrolimus and hydrocortisone in adult atopic
      dermatitis: an immunohistochemical study.
AB  - BACKGROUND: While many studies have demonstrated the efficacy and safety of
      tacrolimus ointment in the treatment of atopic dermatitis (AD), only a few have
      investigated the effects of tacrolimus on inflammatory cells and their cytokine
      gene expression in patients with AD. OBJECTIVES: To characterize further the
      immunophenotype of infiltrating cells and the production of certain cytokines
      before and after treatment with topical tacrolimus and hydrocortisone butyrate.
      METHODS: Nine adult patients with moderate to severe AD were treated with
      tacrolimus ointment, while seven control patients were treated with
      hydrocortisone butyrate ointment. We performed lesional skin biopsies before and
      after treatment. These were stained immunohistochemically with a panel of
      monoclonal antibodies including those to CD1a, CD3, CD4, CD8, myeloperoxidase,
      EG1, EG2, tryptase, interferon-gamma, interleukin (IL)-4, IL-5, IL-12, IL-13,
      receptors for CXC chemokines (CXCR) 3 and 4, and receptor 3 for CC chemokines.
      RESULTS: CD3+, CD4+ and CD8+ lymphocytes, and eosinophil and neutrophil
      granulocytes were significantly reduced in post-treatment tacrolimus specimens,
      while CD1a+ cells and mast cells were not. The expression of cytokines and
      chemokine receptors tested, except for CXCR3, was diminished by tacrolimus
      treatment. Moreover, tacrolimus produced a greater reduction of lymphocytes,
      eosinophils and most cytokines than that induced by hydrocortisone butyrate.
      CONCLUSIONS: Tacrolimus not only inhibits T-lymphocyte proliferation and cytokine
      production, but also plays an important role in the IL-12-induced shift from a T
      helper (Th) 2 to a Th1 cytokine profile that characterizes the development of
      chronic AD. Tacrolimus also demonstrates wider pharmacodynamic effects than
      hydrocortisone.

PMID- 17223873
TI  - Treatment of post-transplant premalignant skin disease: a randomized intrapatient
      comparative study of 5-fluorouracil cream and topical photodynamic therapy.
AB  - BACKGROUND: Organ transplant recipients (OTR) are at high risk of developing
      nonmelanoma skin cancer and premalignant epidermal dysplasia (carcinoma in situ/
      Bowen's disease and actinic keratoses). Epidermal dysplasia is often widespread
      and there are few comparative studies of available treatments. OBJECTIVES: To
      compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with
      topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant
      epidermal dysplasia. METHODS: Eight OTRs with epidermal dysplasia were recruited
      to an open-label, single-centre, randomized, intrapatient comparative study.
      Treatment with two cycles of topical MAL PDT 1 week apart was randomly assigned
      to one area of epidermal dysplasia, and 5-FU cream was applied twice daily for 3
      weeks to a clinically and histologically comparable area. Patients were reviewed
      at 1, 3 and 6 months after treatment. The main outcome measures were complete
      resolution rate (CRR), overall reduction in lesional area, treatment-associated
      pain and erythema, cosmetic outcome and global patient preference. RESULTS: At
      all time points evaluated after completion of treatment, PDT was more effective
      than 5-FU in achieving complete resolution: eight of nine lesional areas cleared
      with PDT (CRR 89%, 95% CI: 0.52-0.99), compared with one of nine lesional areas
      treated with 5-FU (CRR 11%, 95% CI: 0.003-0.48) (P = 0.02). The mean lesional
      area reduction was also proportionately greater with PDT than with 5-FU (100% vs.
      79% respectively). Cosmetic outcome and patient preference were also superior in
      the PDT-treated group. CONCLUSIONS: Compared with topical 5-FU, MAL PDT was a
      more effective and cosmetically acceptable treatment for epidermal dysplasia in
      OTRs and was preferred by patients. Further studies are now required to confirm
      these results and to examine the effect of treating epidermal dysplasia with PDT
      on subsequent development of squamous cell carcinoma in this high risk
      population.

PMID- 17223874
TI  - A follow-up study in 28 patients treated with infliximab for severe recalcitrant
      psoriasis: evidence for efficacy and high incidence of biological autoimmunity.
AB  - BACKGROUND: Infliximab, an antitumour necrosis factor-alpha chimeric monoclonal
      antibody, is effective for the treatment of severe psoriasis. While the induction
      of antinuclear antibodies (ANA) and antidouble-stranded-DNA antibodies (anti
      dsDNA-ab) is frequently observed in patients with rheumatoid arthritis and Crohn
      disease receiving infliximab, the incidence of induced biological and clinical
      autoimmunity remains unknown in the context of psoriasis. OBJECTIVES: To
      investigate biological and clinical signs of autoimmunity in 28 patients
      receiving infliximab for severe, recalcitrant forms of psoriasis, and the
      clinical response to treatment. METHODS: Twenty-eight patients, 15 men and 13
      women (median age 39.4 years) with psoriasis refractory to three or more systemic
      treatments were included. Twenty presented with plaque-type psoriasis [median
      Psoriasis Area and Severity Index (PASI) score 25.9; range 7.2-48], five with
      psoriatic erythroderma (median PASI score 54; range 48-72) and three with
      generalized pustular psoriasis (GPP). Psoriatic arthritis was present in 13
      patients (46.4%). Infliximab 5 mg kg(-1) was given at week (W) 0, W2, W6 and
      every 8 weeks thereafter. Clinical data were assessed at baseline and before each
      infusion. Detection of ANA and of IgM and IgG anti-dsDNA-ab were performed at
      baseline and at W22 by immunofluorescence and enzyme-linked immunosorbent assay,
      respectively. RESULTS: The mean number of infliximab infusions was 5.5 (range 2
      15). Among patients with plaque-type and erythrodermic psoriasis, 17 of 25 (68%)
      and three of five reached a PASI improvement of 75% or more, respectively, while
      rapid improvement of clinical and biological signs was observed in all three
      patients with GPP. The prevalence of positive detection of ANA raised from 12% at
      baseline to 72% at W22 (P = 0.0001), an increase which was also observed for IgM
      anti-dsDNA-ab (68% vs. 0%, P < 0.0001), while no significant change was observed
      for the IgG isotype (16% vs. 0%, P = 0.125). Three patients developed nonerosive
      polyarthritis, without any other criteria for systemic lupus. CONCLUSIONS: The
      incidence of biological autoimmunity is high in patients with refractory
      psoriasis receiving infliximab. The concomitant onset of polyarthritis in three
      cases raises the need to investigate the incidence of autoimmune manifestations
      in psoriatic patients receiving infliximab in further large-scale studies.

PMID- 17223875
TI  - Phase I/II study of topical imiquimod and intralesional interleukin-2 in the
      treatment of accessible metastases in malignant melanoma.
AB  - BACKGROUND: Patients with metastatic skin disease in malignant melanoma can be
      difficult to treat effectively, often requiring repeated treatments with
      different modalities in an attempt to control their disease. Treatment of
      nonsurgically resectable melanoma deposits is unsatisfactory, as they are often
      multiple and recurring. Anecdotal evidence from individual use of imiquimod in
      superficial metastases and intralesional interleukin (IL)-2 in subcutaneous
      deposits suggests that the combination may be more effective in bulky
      subcutaneous disease. OBJECTIVES: To investigate the combination of topical
      imiquimod and, for selected lesions, intralesional IL-2, to treat a small cohort
      of patients with accessible melanoma metastases resistant to other treatments.
      METHODS: Thirteen patients were recruited: all had evidence of multiple cutaneous
      and/or subcutaneous metastases. Imiquimod was applied to the metastases on a
      daily basis for 4 weeks, before the introduction of intralesional IL-2. This was
      injected up to three times a week, into selected lesions, with 0.1 mL injected
      per lesion at a concentration of 3.6 MIU mL(-1), a total of 1 mL being given at
      each session. The treated lesions were assessed individually at intervals of 3
      months. RESULTS: Thirteen patients were treated, with 10 being eligible for
      assessment. In total, 182 lesions were treated: 137 purely cutaneous lesions and
      41 subcutaneous lesions. Overall, a clinical response was seen in 92 lesions
      (50.5%) with 74 (40.7%) of these being a complete response (CR) with 91% of the
      CRs being in the cutaneous lesions. New lesions did appear during the treatment
      course; however, patients with cutaneous disease experienced a marked slowing of
      the appearance of new cutaneous lesions. No cutaneous lesions that responded
      reappeared on cessation of treatment. CONCLUSIONS: The combination of imiquimod
      and IL-2 is effective in controlling this mixed cutaneous and subcutaneous
      disease, and is well tolerated. Imiquimod alone is often enough to elicit a
      response in purely cutaneous lesions. The addition of intralesional IL-2
      increases the response rates in subcutaneous lesions, and in otherwise refractory
      cutaneous lesions.

PMID- 17223876
TI  - An open-label, dose-ranging study of methotrexate for moderate-to-severe adult
      atopic eczema.
AB  - BACKGROUND: Treatment options for moderate-to-severe atopic eczema are limited.
      Although methotrexate (MTX) is a widely used and effective treatment for
      psoriasis, there have been no previous prospective trials of its use in
      refractory atopic eczema, despite a few small, retrospective reports suggesting
      that it is a well-tolerated and effective treatment. OBJECTIVES: We have assessed
      the safety and efficacy of oral MTX in 12 adults with moderate-to-severe atopic
      eczema in an open-label, dose-ranging, prospective trial using objective outcome
      measures. METHODS: All patients had previously received other second-line
      therapies and had disease only partially responsive to potent topical steroids
      and emollients. During the 24-week MTX treatment period, unrestricted use of
      standard topical therapy was permitted. We used an incremental MTX dose regime,
      starting at 10 mg per week (following a 5-mg test dose) and increasing by 2.5 mg
      weekly until response was achieved or treatment was limited by toxicity. Disease
      activity [six area six sign atopic dermatitis (SASSAD) score] was assessed every
      4 weeks during treatment and 12 weeks after stopping MTX. The primary endpoint
      was 24-week change in disease activity. RESULTS: On average, disease activity
      improved by 52% from baseline (95% confidence interval 45-60%). There were
      significant improvements in quality of life, body surface area affected and loss
      of sleep and itch scores. Global response was rated as 'marked improvement' in
      five of 12 and six of 12 patients, by investigators and patients, respectively.
      In all patients, the majority of improvement in disease activity was seen by week
      12, and, interestingly, patients who had not responded well over this period
      despite reaching a dose of 15 mg weekly failed to improve with further dose
      escalation. Only one patient withdrew due to minor adverse effects. MTX was well
      tolerated by the remaining 11 patients, all of whom completed treatment,
      achieving a median dose of 15 mg weekly. Importantly, eight of nine patients had
      a persistent improvement 12 weeks after stopping MTX, with mean disease activity
      remaining 34% below baseline. CONCLUSIONS: We have shown that MTX is an
      effective, well-tolerated treatment for moderate-to-severe atopic eczema, and
      response appears to compare favourably with other second-line therapies. A
      randomized, controlled trial is now warranted.

PMID- 17223877
TI  - Rituximab in autoimmune bullous diseases: mixed responses and adverse effects.
AB  - BACKGROUND: Intolerably high doses of systemic corticosteroids and additional
      immunosuppressants may be required to control disease activity in autoimmune
      bullous skin diseases. New therapeutic options are needed for such patients.
      OBJECTIVES: To determine the efficacy and adverse effects of adjuvant rituximab.
      METHODS: Seven patients with refractory autoimmune blistering diseases (pemphigus
      vulgaris, PV, n = 4; bullous pemphigoid, BP, n = 2; mucous membrane pemphigoid,
      MMP, n = 1) were treated four times with rituximab at an individual dose of 375
      mg m(-2) at weekly intervals. RESULTS: All lesions cleared in three patients (two
      PV, one BP), while they were reduced by more than 50% in three others (two PV,
      one BP). The concomitant immunosuppressive medication was reduced in five
      patients (four PV, one BP). The patient with MMP developed bilateral blindness
      while nasopharyngeal lesions resolved. Three patients (two BP, one PV)
      experienced severe adverse events including fatal pneumonia. CONCLUSIONS:
      Adjuvant B-cell depletion by rituximab is effective in otherwise therapy
      resistant bullous autoimmune disorders but may be associated with substantial
      adverse effects including fatal outcomes.

PMID- 17223878
TI  - p53 codon 72 Pro homozygosity increases the risk of cutaneous melanoma in
      individuals with dark skin complexion and among noncarriers of melanocortin 1
      receptor red hair variants.
AB  - BACKGROUND: p53 has a common polymorphism at amino acid 72, encoding either
      arginine or proline. p53Arg and p53Pro exhibit differences in various biological
      activities, such as cell-cycle arrest and induction of apoptosis. Numerous
      epidemiological studies have examined the role of this polymorphism in several
      human malignancies, including cutaneous cancers, with contradictory results.
      OBJECTIVES: To investigate the germline frequency of p53 codon 72 polymorphism in
      malignant melanoma in a Mediterranean population, and to examine possible
      associations with various clinicopathological factors. METHODS: In this hospital
      based case-control study we used allele-specific polymerase chain reaction for
      p53 codon 72 genotyping in blood specimens from 107 Greek patients with sporadic
      cutaneous melanoma and 145 healthy controls. RESULTS: After adjustment for age,
      sex and phototype the Pro/Pro genotype was associated with increased risk for
      cutaneous melanoma compared with the Arg/Arg genotype (adjusted odds ratio, OR
      3.17, 95% confidence interval, CI 1.03-9.78). This correlation was more
      pronounced in subjects with phototypes III or IV (adjusted OR 9.56, 95% CI 1.56
      58.46), dark skin (adjusted OR 10.96, 95% CI 1.64-73.28), dark eyes (adjusted OR
      8.86, 95% CI 1.69-46.52) and dark hair (adjusted OR 3.17, 95% CI 1.01-9.95), and
      among noncarriers of melanocortin 1 receptor gene (MC1R) red hair polymorphisms
      (adjusted OR 2.99, 95% CI 1.02-8.78). CONCLUSIONS: p53 codon 72 Pro/Pro genotype
      could be a risk factor for the development of melanoma in the Greek population,
      especially in subgroups with darker skin pigmentation, as well as among
      noncarriers of the MC1R red hair polymorphic variants.

PMID- 17223879
TI  - Taxane-induced scleroderma.
AB  - We report five women who presented with scleroderma due to taxanes, mimicking
      systemic sclerosis. All five patients had received taxane chemotherapy for the
      treatment of metastatic breast cancer. Marked oedema began first, followed by
      skin sclerosis occurring mainly at the distal ends of the extremities 6-12 months
      after the administration of taxane in all patients. Skin biopsies showed full
      layer dermal fibrosis with thickened collagen bundles, and perivascular monocytic
      cell infiltration. These cases resemble systemic sclerosis in terms of their
      clinical course and histological findings. However, clinical findings including
      Raynaud's phenomenon and pulmonary fibrosis as well as immunological
      abnormalities associated with systemic sclerosis were not detected in any of the
      patients. Although the mechanisms have not been clarified, it should be noted
      that taxane is causally involved in the formation of scleroderma-like skin
      conditions.

PMID- 17223880
TI  - Perforating folliculitis associated with tumour necrosis factor-alpha inhibitors
      administered for rheumatoid arthritis.
AB  - Perforating dermatoses are characterized by transepithelial elimination of dermal
      structures. We report a 61-year-old man with rheumatoid arthritis who developed a
      perforating folliculitis following the administration of two tumour necrosis
      factor (TNF)-alpha inhibitors, infliximab and etanercept. To our knowledge, no
      perforating disorders have been reported associated with these drugs. This report
      suggests, for the first time, a role for TNF-alpha in the pathogenesis of
      perforating folliculitis.

PMID- 17223881
TI  - Severe psoriasis treated with a new macrolide: everolimus.
AB  - Psoriasis is an immune-mediated disease with a chronic relapsing course, and the
      particularly severe forms that are refractory to traditional therapies are often
      difficult to manage. Everolimus (Certican; Novartis, Basel, Switzerland) is a new
      rapamycin-derived macrolide that is used in the prophylaxis of rejection in heart
      and kidney transplant patients. The mechanism underlying its immunosuppressant
      and antiproliferative activity is different from, but complementary to, that of
      calcineurin inhibitors such as ciclosporin. We describe a woman with severe
      psoriasis treated with everolimus combined with subtherapeutic doses of
      ciclosporin.

PMID- 17223883
TI  - Sebaceous tumours contain a subpopulation of cells expressing the keratin 15 stem
      cell marker.

PMID- 17223882
TI  - Familial cutaneous collagenomas resulting from a novel mutation in LEMD3.

PMID- 17223884
TI  - Naevus lipomatosus superficialis: a case report with a 2p24 deletion.

PMID- 17223885
TI  - Necrotic livedo after vertebroplasty.

PMID- 17223886
TI  - Periorbital pigmented and reticulated junctional melanocytic naevus: a report of
      two cases.

PMID- 17223887
TI  - Photodynamic therapy for infected leg ulcers.

PMID- 17223888
TI  - Isotretinoin-induced pleuritic chest pain.

PMID- 17223889
TI  - Psoriasis after cord blood stem cell transplantation.

PMID- 17223890
TI  - Stress responsiveness in patients with psoriasis.

PMID- 17223891
TI  - Acute graft-versus-host disease (GVHD) overlapping chronic GVHD after reinduction
      chemotherapy.

PMID- 17223892
TI  - Ciclosporin use in toxic epidermal necrolysis.

PMID- 17223893
TI  - Klippel-Trenaunay syndrome showing hypotrophy of the affected arm.

PMID- 17223894
TI  - Incontinentia pigmenti in a newborn with a novel nonsense mutation in the NEMO
      gene.

PMID- 17223895
TI  - A useful tip for direct microscopy.

PMID- 17223896
TI  - Nicorandil-induced leg ulceration.

PMID- 17223897
TI  - Paraneoplastic neutrophilic figurate erythema.

PMID- 17223898
TI  - Surgical treatment of axillary hyperhidrosis.

PMID- 17223899
TI  - Treatment of Fordyce spots with 5-aminolaevulinic acid-photodynamic therapy.

PMID- 17223900
TI  - Caspase-dependent cleavage of desmoglein 1 depends on the apoptotic stimulus.

PMID- 17223901
TI  - Infliximab-induced acne: report of two cases.

PMID- 17223902
TI  - Four millimetres: a variable measurement?

PMID- 17223903
TI  - Human papillomavirus reactivation following topical tacrolimus therapy of
      anogenital lichen sclerosus.

PMID- 17223904
TI  - Delayed diagnosis of dyskeratosis congenita in a 40-year-old woman with multiple
      head and neck squamous cell carcinomas.

PMID- 17223905
TI  - The nature of solar (actinic) keratosis.

PMID- 17223908
TI  - Charge differences between in vivo deposits in immunoglobulin light chain
      amyloidosis and non-amyloid light chain deposition disease.
AB  - Immunoglobulin light chain amyloidosis (AL) and non-amyloid light chain
      deposition disease (NALCDD) are different forms of protein aggregation disorders
      that may occur in plasma cell dyscrasias with dysproteinemia. In systemic AL, the
      deposits are fibrillar and patchy in distribution, within and amongst different
      organs, whereas in NALCDD, the deposits are granular and diffusely distributed in
      systemic basement membranes, suggesting different mechanisms of aggregation and
      deposition. Previous evidence, that charge differences between the light chains
      in AL and NALCDD might account for their different phenotypes, prompted the
      present study, which compared the isoelectric points (pIs) of AL and NALCDD
      protein deposits extracted from human tissues. The pI profiles (5.2-8.8) of
      polypeptides in AL deposits were heterogenous in four cases, with a spread of
      both anionic and cationic isoforms; in contrast, in three of NALCDD the pI
      profiles (8.2-8.8) were homogeneous and restricted in the cationic range. These
      in vivo findings in human disease, together with other reported in vitro and in
      vivo experimental data, suggest that the fibrillar deposits in AL may form by
      electrostatic interaction between oppositely charged polypeptides, whereas the
      granular deposits in NALCDD form by the binding of cationic polypeptides to
      anionic proteoglycans sites in basement membranes.

PMID- 17223909
TI  - Bone mass density in adults with sickle cell disease.
AB  - Sickle cell disease (SCD) leads to many complications including osteoporosis and
      osteopenia. We studied the prevalence and predisposing factors of low bone mass
      density (BMD) in adults with SCD. In this retrospective study, dual X-ray
      absorptiometry bone scans were used to determine BMD in the lumbar spine, femoral
      neck and ultra distal radius of 103 patients (73 females, 30 males, aged 15-80
      years). Chart reviews and a patient questionnaire were used to collect patient
      characteristics, disease course and severity, and low BMD risk factors. The 79.6%
      of patients (mean age 36.5 +/- 12.5 years) had an abnormal BMD, with a
      predilection for the lumbar spine (P = 0.001). Analysis by 3 (low BMD versus very
      low BMD versus normal) or by 2 groups (abnormal versus normal) showed that
      abnormal BMD was associated with lower body mass index (BMI) (P = 0.003), lower
      Hb level (P = 0.001) and higher ferritin (P = 0.003). Low BMD patients were more
      likely to be SS, SC or Sbeta(0)thal than Sbeta(+)thal (P = 0.022). Abnormal BMD
      was not related to age, sex, menarche, SCD complications, number of crises, iron
      overload, treatment with hydroxycarbamide or desferal, renal disease, smoking or
      alcohol. Patients treated with hydroxycarbamide for at least 6 months were more
      likely to have an abnormal BMD. In this SCD population, abnormal BMD seemed to be
      independent of sex, age and menopause, whereas BMI, ferritin level, Hb type and
      level appeared to play a major role.

PMID- 17223910
TI  - Effect of myeloablative bone marrow transplantation on growth in children with
      sickle cell anaemia: results of the multicenter study of haematopoietic cell
      transplantation for sickle cell anaemia.
AB  - Although haematopoietic cell transplantation (HCT) is curative for sickle cell
      anaemia (SCA), concerns about its short- and long-term toxicities limit its
      application. A potential toxicity is an adverse effect on growth. To identify an
      HCT growth effect, serial height and weight measurements from 53 children and
      adolescents with SCA after receiving a transplant were compared to historical
      controls. Hierarchical Linear Models for longitudinal data were used for
      analysis. In general growth was not impaired by HCT for SCA in young children;
      however, diminished growth may occur if HCT is carried out near or during the
      adolescent growth spurt.

PMID- 17223913
TI  - JAK2 (V617F) mutation in healthy individuals.

PMID- 17223912
TI  - Cancer-testis antigens in haematological malignancies.
AB  - Immunotherapy is an attractive therapeutic option for patients with
      haematological malignancies. Until recently, the progress in the development of
      tumour vaccines for haematological malignancies had been slow due to the lack of
      suitable targets. Cancer-testis (CT) antigens are potentially suitable molecules
      for tumour vaccines of haematological malignancies because of their high
      immunogenicity in vivo and their relatively restricted normal tissue
      distribution. This review evaluates the properties and potential functions of CT
      antigens. We discuss the expression of CT antigens in patient with haematological
      malignancies and provide evidence in support of their immunogenicity in vivo in
      these patients. We also address the role of 'epigenetic' regulation of CT
      antigens in haematological malignancies and how hypomethylating agents could
      induce the expression of some of these antigens in tumour cells to overcome the
      problem of heterogeneity of expression of the antigen within individual tumour
      specimens. Data implicating the interaction of the promoter genes of some of
      these CT antigens with the MeCP2 protein also suggest the potential role of the
      histone deacetylase inhibitors in inducing antigen expression in tumour cells.
      Finally, we discuss the direction of future research in advancing the development
      of tumour vaccines for haematological malignancies.

PMID- 17223914
TI  - Epstein-Barr virus T-cell immunity despite rituximab.
AB  - Immunosuppression following solid organ transplantation results in impaired T
      cell immunity and risk of Epstein-Barr virus (EBV)-positive post-transplant
      lymphoproliferative disorders (PTLD). The B-cell targeting antibody rituximab has
      efficacy in PTLD. As B cells are the principle reservoir for EBV, we investigated
      the effect of rituximab on the persistence of EBV-specific CD8(+) T-cell
      immunity. To avoid the confounding factor of concurrent immunosuppression to
      prevent transplant rejection, immunity was analysed in non-transplanted lymphoma
      patients (i.e. a non-PTLD setting). Cytomegalovirus-specific T-cell immunity was
      assessed as an internal control. Our data demonstrated that circulating B cells
      were not critical for maintaining EBV-specific T-cell immunity.

PMID- 17223915
TI  - Abnormalities of chromosome 1p/q are highly associated with chromosome 13/13q
      deletions and are an adverse prognostic factor for the outcome of high-dose
      chemotherapy in patients with multiple myeloma.
AB  - The prognostic value of chromosomal abnormalities was studied in untreated
      multiple myeloma patients who were registered into a prospective randomised
      multicentre phase 3 study for intensified treatment (HOVON24). A total of 453
      patients aged less than 66 years with stage II and III A/B disease were
      registered in the clinical study. Cytogenetic analysis was introduced as a
      standard diagnostic assay in 1998. It was performed at diagnosis in 160 patients
      and was successful in 137/160 patients (86%). An abnormal karyotype was observed
      in 53/137 (39%) of the patients. Abnormalities of chromosome 1p and 1q were found
      in 19 (36% of patients with an abnormal karyotype) and 21 patients (40%). There
      was a strong association between chromosome 1p and/or 1q abnormalities and
      deletion of chromosome 13 or 13q (n = 27, P < 0.001). Patients with karyotypic
      abnormalities had a significantly shorter overall survival (OS) than patients
      with normal karyotypes. Complex abnormalities, hypodiploidy, chromosome 1p
      abnormalities, chromosome 1q abnormalities, and chromosome 13 abnormalities were
      associated with inferior OS on univariate analysis, as well as after adjustment
      for other prognostic factors. In conclusion, chromosome 13 abnormalities and
      chromosome 1p and/or 1q abnormalities were highly associated, and are risk
      factors for poor outcome after intensive therapy in multiple myeloma.

PMID- 17223916
TI  - Reduction of high fetal loss rate by anticoagulant treatment during pregnancy in
      antithrombin, protein C or protein S deficient women.
AB  - Hereditary thrombophilia is associated with an increased risk of fetal loss.
      Assuming that fetal loss is due to placental thrombosis, anticoagulant treatment
      might improve pregnancy outcome. In an observational family cohort study, we
      prospectively assessed the effects of anticoagulant drugs on fetal loss rates in
      women with hereditary deficiencies of antithrombin, protein C or protein S. The
      cohort contained 376 women (50 probands and 326 deficient or non-deficient
      relatives). Probands were consecutive deficient patients with venous
      tromboembolism. Thromboprophylaxis during pregnancy was recommended in deficient
      women, irrespective of prior venous thromboembolism, and in non-deficient women
      with prior venous thromboembolism. Outcome of first pregnancy was analysed in 55
      eligible women. Of 37 deficient women, 26 (70%) received thromboprophylaxis
      during pregnancy, compared with three of 18 (17%) non-deficient women. Fetal loss
      rates were 0% in deficient women with thromboprophylaxis versus 45% in deficient
      women without (P = 0.001) and 7% in non-deficient women without
      thromboprophylaxis (P = 0.37). The adjusted relative risk of fetal loss in women
      who received thromboprophylaxis versus women who did not was 0.07 (95% confidence
      interval 0.001-0.7; P = 0.02). Our data suggest that anticoagulant treatment
      during pregnancy reduces the high fetal loss rate in women with hereditary
      deficiencies of antithrombin, protein C or protein S.

PMID- 17223917
TI  - Detection and follow-up of fibroblast growth factor receptor 3 expression on bone
      marrow and circulating plasma cells by flow cytometry in patients with t(4;14)
      multiple myeloma.
AB  - The t(4;14)(p16;q32) translocation, found in 15% of multiple myeloma (MM) cases,
      indicates a poor prognosis. Plasma cells (PC) with t(4;14) ectopically express
      the fibroblast growth factor receptor 3 (FGFR3) tyrosine kinase receptor, which
      has potential transforming activity and may represent a therapeutic target. To
      detect FGFR3 protein expression, bone marrow (BM) aspirate from 200 consecutive
      newly diagnosed (n = 116) or relapsing (n = 74) MM patients was studied by flow
      cytometry (FC) using anti-CD138 and anti-FGFR3 antibodies. FC data was compared
      to real time quantitative-polymerase chain reaction (RQ-PCR) of the IGH-MMSET and
      FGFR3 transcripts. An IGH-MMSET transcript was found in 24/200 patients (12%). In
      20 of these, FC detected CD138(+)/FGFR3(+) cells. No expression of FGFR3 was
      detected in the 4 FGFR3(-) cases by RQ-PCR. FGFR3 was never expressed on PC
      without t(4;14). Circulating PC (CPC) were detected in patients with (11/11) and
      patients without (13/41) t(4;14). In 2/8 t(4;14) cases studied longitudinally,
      coexisting FGFR3(+) and FGFR3(-) CPC were observed. Fluorescent in situ
      hybridisation (FISH) analysis of the FGFR3(-) subclones showed deletion of the
      der(14) in one patient. In conclusion, as a supplemental method to RQ-PCR or
      FISH, FC analysis of FGFR3 expression is a reliable and routinely available
      method for the detection and management of new therapeutic approaches of t(4;14)
      MM.

PMID- 17223918
TI  - Adoptive transfer of syngeneic T cells in HIV-1 discordant twins indicates rapid
      regulation of T-cell homeostasis.
AB  - The safety and efficacy of adoptive T-cell transfer (ATT) was tested in the
      context of viral suppression in syngeneic twins discordant for human
      immunodeficiency virus type 1 (HIV-1) infection. Human leucocyte antigen-matched
      T cells of seven HIV-negative twins were obtained by lymphapheresis and
      immediately transfused into the HIV-infected sibling. Four twins received 12 ATTs
      each, with a mean of 2.10 +/- 0.97 x 10(9) CD4(+) T cells and 1.74 +/- 0.81 x
      10(9) CD8(+) T cells. Additional transfers were performed in three more twin
      pairs to study the short-term kinetics of transfused syngeneic T cells. Mean
      CD4(+) T-cell counts increased significantly, by 0.133 +/- 0.136 x 10(9) cells/l
      at 1 h and 0.144 +/- 0.12 x 10(9) cells/l at 3 h post-transfusion (P < 0.0001).
      Short-term kinetic studies suggested a rapid clearance of transferred T cells
      from the peripheral blood within minutes due to a distribution to marginal pools.
      After a mean follow up of 39 months, however, a sustained increase of the mean
      CD4(+) T-cell count was observed (from 0.232 x 10(9) to 0.523 x 10(9) cells/l)
      without changes of plasma viraemia. We conclude that ATT combined with highly
      active antiretroviral therapy is safe and leads to a considerable increase in
      CD4(+) T-cell numbers. The clearance kinetics of the transfused cells from
      peripheral blood indicates a very rapid regulation of T-cell homeostasis in HIV
      infection.

PMID- 17223919
TI  - The haematopoietic cell transplantation comorbidity index score is predictive of
      early death and survival in patients over 60 years of age receiving induction
      therapy for acute myeloid leukaemia.
AB  - The haematopoietic cell transplantation comorbidity index (HCTCI) predicts
      nonrelapse mortality and overall survival (OS) post-stem cell transplantation.
      HCTCI scores were assessed in 177 patients over 60 years of age receiving acute
      myeloid leukaemia (AML) induction therapy. HCTCI score was 0 in 22% of patients,
      1-2 in 30%, and > or =3 in 48%. In patients with scores of 0, 1-2, or > or =3,
      early death rates were 3%, 11% and 29% (P < 0.001) respectively; median OS was
      45, 31 and 19 weeks (P = 0.04) respectively. The HCTCI score is predictive of
      early death rates and OS in older patients receiving AML induction therapy.

PMID- 17223921
TI  - Repeat prostate biopsy in the prostate, lung, colorectal and ovarian cancer
      screening trial.
AB  - OBJECTIVE: To determine patterns of repeat prostate biopsy in a cohort of men
      undergoing prostate cancer screening who have a negative initial biopsy. SUBJECTS
      AND METHODS: The Prostate, Colorectal, Lung, and Ovarian (PLCO) cancer screening
      trial is an ongoing study the prostate component of which consists of six annual
      screens with measurements of prostate-specific antigen (PSA) level and a digital
      rectal examination (DRE). The diagnostic follow-up of positive screening results
      is done by the subject's healthcare provider outside the purview of the PLCO. We
      analysed the experience of repeat biopsy in men in the PLCO with an initial
      negative biopsy. Men were divided by indication for initial biopsy into those
      with suspicious PSA levels and those with suspicious DRE findings. RESULTS: The
      probability of having a repeat biopsy within 3 years of initial biopsy was 43%
      for 1736 men with suspicious PSA levels and 13% for 1025 men with suspicious DRE
      findings. Rates of third and fourth biopsy after a previous negative biopsy were
      similar to the initial repeat biopsy rate in PSA-positive men. Most men had a
      repeat biopsy only after having an additional round of screening. The PSA level
      and PSA velocity determined after initial biopsy were independent risk factors
      for a repeat biopsy, both in PSA-positive and DRE-positive men. High-grade
      prostatic intraepithelial neoplasia was a risk factor for repeat biopsy before
      any repeat PSA or DRE testing. CONCLUSION: The experience of this cohort should
      be generally representative of patterns of care for repeat biopsy in men
      undergoing periodic screening. These data can provide context to the debate over
      optimum practices for repeat biopsy.

PMID- 17223922
TI  - The utility of magnetic resonance imaging and spectroscopy for predicting
      insignificant prostate cancer: an initial analysis.
AB  - OBJECTIVE: To design new models that combine clinical variables and biopsy data
      with magnetic resonance imaging (MRI) and MR spectroscopic imaging (MRSI) data,
      and assess their value in predicting the probability of insignificant prostate
      cancer. PATIENTS AND METHODS: In all, 220 patients (cT stage T1c or T2a, prostate
      specific antigen level <20 ng/mL, biopsy Gleason score 6) had MRI/MRSI before
      surgery and met the inclusion criteria for the study. The probability of
      insignificant cancer was recorded retrospectively and separately for MRI and
      combined MRI/MRSI on a 0-3 scale (0, definitely insignificant; - 3, definitely
      significant). Insignificant cancer was defined from surgical pathology as organ
      confined cancer of </= 0.5 cm(3) with no poorly differentiated elements. The
      accuracy of predicting insignificant prostate cancer was assessed using areas
      under receiver operating characteristic curves (AUCs), for previously reported
      clinical models and for newly generated MR models combining clinical variables,
      and biopsy data with MRI data (MRI model) and MRI/MRSI data (MRI/MRSI model).
      RESULTS: At pathology, 41% of patients had insignificant cancer; both MRI (AUC
      0.803) and MRI/MRSI (AUC 0.854) models incorporating clinical, biopsy and MR data
      performed significantly better than the basic (AUC 0.574) and more comprehensive
      medium (AUC 0.726) clinical models. The P values for the differences between the
      models were: base vs medium model, <0.001; base vs MRI model, <0.001; base vs
      MRI/MRSI model, <0.001; medium vs MRI model, <0.018; medium vs MRI/MRSI model,
      <0.001. CONCLUSIONS: The new MRI and MRI/MRSI models performed better than the
      clinical models for predicting the probability of insignificant prostate cancer.
      After appropriate validation, the new MRI and MRI/MRSI models might help in
      counselling patients who are considering choosing deferred therapy.

PMID- 17223923
TI  - Distraction in the urology operating theatre.

PMID- 17223924
TI  - Protein export from Plasmodium parasites.
AB  - Many prokaryotic and eukaryotic intracellular pathogens survive by altering the
      host cell through the export of proteins. In contrast to the well-studied
      prokaryotic export systems, knowledge of protein export in eukaryotic pathogens
      is scant. The recent discovery that a short protein sequence targets a protein
      for export from the malaria parasite Plasmodium falciparum has shed light on the
      possible mechanism of proteins export and has allowed the preliminary
      identification of several hundred exported proteins. Among the exported proteins
      are the members of the paralogous protein families, previously identified
      exported proteins and many uncharacterized proteins. The interaction of the
      parasite with the host cell is thus much more complex, and involves more parasite
      proteins, than previously thought.

PMID- 17223925
TI  - Golgi biogenesis in simple eukaryotes.
AB  - The accurate duplication of cellular organelles is important to ensure
      propagation through successive generations. The semi-conserved replication of DNA
      and DNA-containing organelles has been well studied, but the mechanisms used to
      duplicate most other organelles remain elusive. These include the centrosomes,
      which act as microtubule organizing centres during interphase and orient the
      mitotic spindle poles during mitosis. Centrosomes can also act as basal bodies,
      nucleating the growth of cilia or flagella. Even less understood are the
      mechanisms used to duplicate membrane-bound organelles that do not contain DNA.
      These include organelles involved in the secretory pathway such as the
      endoplasmic reticulum and the Golgi apparatus. This review will summarize the
      current knowledge of Golgi biogenesis in simple eukaryotic organisms, in
      particular, two protozoan parasites, Toxoplasma gondii and Trypanosoma brucei.

PMID- 17223927
TI  - Accelerated immunopathological response of mice infected with Mycobacterium
      tuberculosis disrupted in the mce1 operon negative transcriptional regulator.
AB  - Mycobacterium tuberculosis causes a variety of clinical outcomes determined by
      host as well as bacterial factors. M. tuberculosis disrupted in the mce1 operon
      causes increased mortality in immunocompetent mice. This operon is negatively
      regulated by mce1R (Rv0165c). We studied the role of mce1R in infection outcome
      in mice. At 5 x 10(4) tail vein infectious dose, the median survival time (MST)
      of mice infected with the mce1R mutant M. tuberculosis H37Rv was 293 days, while
      mice infected with the wild-type H37Rv survived more than 350 days (P < 0.0001).
      At a higher dose (5 x 10(6)), the MST of mutant-infected mice was 32 days,
      compared with 127 days for wild type-infected mice (P < 0.0001). With either tail
      vein or aerosol infection, mutant-infected mice developed larger granulomatous
      lesions in their lungs than mice infected with the wild type. Mutant-infected
      mice were unable to control the bacterial burden in the first 4 weeks of
      infection, but even after achieving control later, these mice succumbed to
      granulomatous pneumonia. These observations suggest that the early deregulated
      expression of the mce1 operon products determines later granulomatous tissue
      response. mce1 operon may homeostatically regulate the cell wall architecture in
      vivo that elicits a steady-state granuloma tissue response permitting M.
      tuberculosis to establish a long-term infection.

PMID- 17223926
TI  - The global regulator Lrp contributes to mutualism, pathogenesis and phenotypic
      variation in the bacterium Xenorhabdus nematophila.
AB  - Xenorhabdus nematophila is a Gram-negative bacterium that leads both pathogenic
      and mutualistic lifestyles. In this study, we examine the role of Lrp, the
      leucine-responsive regulatory protein, in regulating both of these lifestyles.
      lrp mutants have attenuated virulence towards Manduca sexta insects and are
      defective in suppression of both cellular and humoral insect immunity. In
      addition, an lrp mutant is deficient in initiating colonization of and growth
      within mutualistic host nematodes. Furthermore, nematodes reared on lrp mutant
      lawns exhibit decreased overall numbers of nematode progeny. To our knowledge,
      this is the first demonstration of virulence attenuation associated with an lrp
      mutation in any bacterium, as well as the first report of a factor involved in
      both X. nematophila symbioses. Protein profiles of wild-type and mutant cells
      indicate that Lrp is a global regulator of expression in X. nematophila,
      affecting approximately 65% of 290 proteins. We show that Lrp binds to the
      promoter regions of genes known to be involved in basic metabolism, mutualism and
      pathogenesis, demonstrating that the regulation of at least some host interaction
      factors is likely direct. Finally, we demonstrate that Lrp influences aspects of
      X. nematophila phenotypic variation, a spontaneous process that occurs during
      prolonged growth in stationary phase.

PMID- 17223928
TI  - Adherent-invasive Escherichia coli isolated from Crohn's disease patients induce
      granulomas in vitro.
AB  - Adherent-invasive Escherichia coli (AIEC) have been shown to be highly associated
      with ileal Crohn's disease (CD). AIEC survive within infected macrophages,
      residing within the phagolysosomal compartment where they take advantage of the
      low pH to replicate extensively. We investigated whether, like the tuberculous
      bacillus which also persists within macrophages, AIEC LF82 induces the formation
      of granulomas, which are a common histopathological feature of CD. For this
      purpose, we have taken advantage of an in vitro model of human granulomas that we
      recently developed, based on blood-derived mononuclear cells. We demonstrated
      that AIEC LF82 induces aggregation of infected macrophages, fusion of some of
      them to form multinucleated giant cells and subsequent recruitment of
      lymphocytes. Light microscopy and scanning electron microscopy analysis of the
      cell aggregates confirmed their granuloma features. This was further confirmed by
      histological analysis of granuloma sections. Noteworthy, this phenomenon can be
      reproduced by soluble protein extracts of AIEC LF82 coated onto beads. Although
      the cell aggregates not completely mimic natural CD-associated granulomas, they
      are very similar to early stages of epithelioid granulomas.

PMID- 17223929
TI  - Ceramide as a TLR4 agonist; a putative signalling intermediate between
      sphingolipid receptors for microbial ligands and TLR4.
AB  - Mucosal Toll-like receptors (TLRs) respond to pathogens, but remain inert to the
      indigenous flora, suggesting that the TLRs can receive pathogen-specific signals.
      For example, TLR4 signalling is activated in CD14-negative epithelial cells by P
      fimbriated, uropathogenic Escherichia coli, but not by lipopolysaccharide. The
      fimbriae use glycosphingolipids as recognition receptors and there is release of
      ceramide, which is the membrane-anchoring domain of the receptors. In this study,
      ceramide was identified as a TLR4 agonist and as a putative signalling
      intermediate between the glycosphingolipid recognition receptors and TLR4.
      Exogenous ceramide activated a TLR4-dependent epithelial cell response, as shown
      by exposing stably transfected TLR4-positive or -negative human embryonal kidney
      cells to C2 and C6 ceramide. A similar, TLR4-dependent response occurred after
      deliberate release of endogenous long-chained ceramide with sphingomyelinase.
      Microbial ligands with glycosphingolipid specificity (P fimbriae or the B subunit
      of Shiga toxin) were shown to increase the levels of ceramide and to trigger a
      TLR4-dependent response in epithelial cells. The results show that ceramide
      activates TLR4 signalling and suggest that this mechanism might allow pathogens
      to elicit mucosal TLR4 responses by perturbing sphingolipid receptors for
      virulence ligands like P fimbriae.

PMID- 17223930
TI  - Contribution of toxins to the pathogenesis of inhalational anthrax.
AB  - Inhalational anthrax is a life-threatening infectious disease of considerable
      concern, especially as a potential bioterrorism agent. Progress is gradually
      being made towards understanding the mechanisms used by Bacillus anthracis to
      escape the immune system and to induce severe septicaemia associated with
      toxaemia and leading to death. Recent advances in fundamental research have
      revealed previously unsuspected roles for toxins in various cell types. We
      summarize here pathological data for animal models and macroscopic histological
      examination data from recent clinical records, which we link to the effects of
      toxins. We describe three major steps in infection: (i) an invasion phase in the
      lung, during which toxins have short-distance effects on lung phagocytes; (ii) a
      phase of bacillus proliferation in the mediastinal lymph nodes, with local
      effects of toxins; and (iii) a terminal, diffusion phase, characterized by a high
      blood bacterial load and by long-distance effects of toxins, leading to host
      death. The pathophysiology of inhalational anthrax thus involves interactions
      between toxins and various cell partners, throughout the course of infection.

PMID- 17223931
TI  - Plasmodium sporozoites trickle out of the injection site.
AB  - Plasmodium sporozoites make a remarkable journey from the skin, where they are
      deposited by an infected Anopheline mosquito, to the liver, where they invade
      hepatocytes and develop into exoerythrocytic stages. Although much work has been
      done to elucidate the molecular mechanisms by which sporozoites invade
      hepatocytes, little is known about the interactions between host and parasite
      before the sporozoite enters the blood circulation. It has always been assumed
      that sporozoites rapidly exit the injection site, making their interactions with
      the host at this site, brief and difficult to study. Using quantitative PCR, we
      determined the kinetics with which sporozoites leave the injection site and
      arrive in the liver and found that the majority of infective sporozoites remain
      in the skin for hours. We then performed sub-inoculation experiments which
      confirmed these findings and showed that the pattern of sporozoite exit from the
      injection site resembles a slow trickle. Last, we found that drainage of
      approximately 20% of the sporozoite inoculum to the lymphatics is associated with
      a significant enlargement of the draining lymph node, a response not observed
      after intravenous inoculation. These findings indicate that there is ample time
      for host and parasite to interact at the inoculation site and are of relevance to
      the pre-erythrocytic stage malaria vaccine effort.

PMID- 17223933
TI  - Magnetic resonance colonography vs computed tomography colonography for the
      diagnosis of colorectal cancer: an indirect comparison.
AB  - OBJECTIVE: The primary aim of this study was to use meta-regression techniques to
      compare the diagnostic accuracy of computed tomography colonography (CTC) and
      magnetic resonance colonography (MRC), compared with conventional colonoscopy for
      patients presenting with colorectal cancer (CRC). METHOD: Quantitative meta
      analysis was performed using prospective studies reporting comparative data
      between CTC and MRC individually to conventional colonoscopy. Study quality was
      assessed and sensitivities, specificities, diagnostic odds ratios (DOR) were
      calculated. Summary receiver operating characteristic (SROC) curves and
      sensitivity analysis were utilized. Meta-regression was used to indirectly
      compare the two modalities following adjustment for patient and study
      characteristics. RESULTS: Overall sensitivity and specificity for CTC (0.96, 95%
      CI 0.92-0.99; 1.00, 95% CI 0.99-1.00 respectively) and MRC (0.91, 95% CI 0.79
      0.97; 0.98, 95% CI 0.96-0.99 respectively) for the detection of CRC was similar.
      Meta-regression analysis showed no significant difference in the diagnostic
      accuracy of both modalities (beta=-0.64, P=0.37 and 95% CI of 0.12-2.39). Both
      tests showed high area under the SROC curve (CTC=0.99; MRC=0.98), with high DORs
      (CTC=1461.90, 95% CI 544.89-3922.30; MRC=576.41, 95% CI 135.00-2448.56). Factors
      that enhanced the overall accuracy of MRC were the use intravenous contrast,
      faecal tagging and exclusion of low-quality studies. No factors improved
      diagnostic accuracy from CTC except studies with more than 100 patients
      (AUC=1.00, DOR=2938.35, 95%CI 701.84-12 302.91). CONCLUSION: This meta-analysis
      suggested that CTC and MRC have similar diagnostic accuracy for detecting CRC.
      Study quality, size and intravenous/intra-luminal contrast agents affect
      diagnostic accuracies. For an exact comparison to be made, studies evaluating
      CTC, MRC and colonoscopy in the same patient cohort would be necessary.

PMID- 17223934
TI  - Assessing the evidence for an association between circumferential tumour
      clearance and local recurrence after resection of rectal cancer.
AB  - OBJECTIVE: Circumferential resection margin involvement (CRMI) after resection of
      rectal cancer is regarded as a risk factor for local recurrence. We have been
      able to identify only nine peer-reviewed English-language publications which
      focus primarily on this association, and they report widely differing rates of
      local recurrence. The aims of this study were to review possible reasons for this
      variability and to assess the evidence for the micrometrically measured threshold
      defining CRMI. METHOD: Methodological and statistical evaluation of relevant
      literature. RESULTS: Several factors which could account for this variability are
      discussed including the nature of the patient series, surgical technique,
      curative vs palliative resections, pathology technique, the definition of CRMI,
      adjuvant therapy, tumour stage, definition and ascertainment of local recurrence,
      length of follow-up and method of analysis. The objective evidence for the
      conventional definition of CRMI as tumour 1 mm or less from a circumferential
      margin is considered along with the evidence supporting a recent proposal that
      the margin be extended to 2 mm or less. The evidence is numerically weak in both
      cases and we believe that neither definition should be set in concrete at this
      stage. CONCLUSION: Pending further research, we recommend that routine pathology
      reports should record frank tumour transection, if present, or otherwise report
      the histological width of the margin between the tumour and the nearest
      circumferential line of resection in millimetres. The definition of CRMI should
      be simply histological evidence of tumour in a line of resection, that is, a
      margin of 0 mm. The definition of CRMI as a margin of <or=1 mm should not be
      adopted as a basis for assessing the quality of surgery.

PMID- 17223936
TI  - Sacral nerve stimulation induces pan-colonic propagating pressure waves and
      increases defecation frequency in patients with slow-transit constipation.
AB  - OBJECTIVE: Colonic propagating sequences are important for normal colonic transit
      and defecation. The frequency of these motor patterns is reduced in slow-transit
      constipation. Sacral nerve stimulation (SNS) is a useful treatment for fecal and
      urinary incontinence. A high proportion of these patients have also reported
      altered bowel function. The effects of SNS on colonic propagating sequences in
      constipation are unknown. Our aims were to evaluate the effect of SNS on colonic
      pressure patterns and evaluate its therapeutic potential in severe constipation.
      METHOD: In eight patients with scintigraphically confirmed slow-transit
      constipation, a manometry catheter (16 recording sites at 7.5 cm intervals) was
      positioned colonoscopically and the tip fixed in the caecum. Temporary electrodes
      (Medtronic) were implanted in the S2 and S3 sacral nerve foramina under general
      anaesthesia. In the fasted state, 14 Hz stimulation was administered and four
      sets of parameters (pulse width 300 or 400 micros; S2 and S3) were tested in four
      2-h epochs, in random order, over 2 days. Patients were then discharged home with
      the sacral wires in situ and a 3-week trial stimulation commenced during which
      patients completed a daily stool diary. RESULTS: When compared with basal
      activity, electrical stimulation to S3 significantly increased pan-colonic
      antegrade propagating sequence (PS) frequency (5.4 +/- 4.2 vs 11.3 +/- 6.6 PS/h;
      P=0.01). Stimulation at S2 significantly increased retrograde PSs (basal 2.6 +/-
      1.8 vs SNS 5.6 +/- 4.8 PS/h; P=0.03). During the subsequent three-week trial
      (continuous stimulation), six of eight reported increased bowel frequency with a
      reduction in laxative usage. CONCLUSION: These data demonstrate that SNS induces
      pan-colonic propagating pressure waves and therefore shows promise as a potential
      therapy for severe refractory constipation.

PMID- 17223937
TI  - Tissue factor and vascular endothelial growth factor expression in colorectal
      cancer: relation with cancer recurrence.
AB  - OBJECTIVE: This study was undertaken to quantify tissue factor (TF) and vascular
      endothelial growth factor (VEGF) in colorectal cancer and to evaluate their
      possible relationship with recurrence. METHOD: TF and VEGF were measured by
      enzyme-linked immunosorbent assay in surgical tumour specimens and normal mucosa
      from 50 consecutive patients with colorectal cancer who were followed up for 3
      years for the assessment of disease recurrence. RESULTS: TF and VEGF antigens
      were detected in all tumour samples. VEGF, but not TF, was much higher in tumour
      than in normal mucosa (P < 0.0001), as also confirmed by measurement of specific
      mRNAs. There was a strong correlation between TF and VEGF antigens (P < 0.0005)
      in tumour tissue but not in normal mucosa. Neither protein was related to tumour
      stage, grade or size. Local or distant recurrence was statistically related to
      pTNM stage. High VEGF, but not TF, levels in tumour extracts were associated with
      an increased risk of recurrence both by univariate (RR, 4.00, 95% CI: 1.45-11.0)
      and multivariate analyses (RR, 3.65, 95% CI: 1.33-10.0). CONCLUSION: These
      findings suggest that VEGF content in colorectal cancer is an independent risk
      factor for tumour recurrence and might help select patients who might benefit
      from adjuvant therapy.

PMID- 17223938
TI  - Ileal pouch-anal anastomosis: the Australasian experience.
AB  - OBJECTIVE: The aim of this project was to establish and maintain an internet
      based database of all ileal pouch procedures performed in major centres in
      Australasia. METHOD: The initial three colorectal units contributing data are
      Auckland, northern Brisbane and Central Sydney Area Health Service. A web-based
      database was designed. The data collection method was tested on a subgroup of 20
      patients to ensure functionality. Data were collected in five main categories:
      patient demographics, preoperative data, operative details, postoperative
      complications and functional results. RESULTS: Initial data are presented for 516
      patients [363 J, (70%), 133 W (26%), 16 S pouches (3%)]. There were two deaths
      within 30 days (0.4%). The anastomotic leak rate overall, in handsewn (HSA) and
      stapled anastomoses (SA) respectively was 5.0%, 8.5% and 3.3% (P=0.02 for
      difference HSA vs SA). Incidence of pouchitis was 20% (ulcerative colitis 23%,
      Crohn's disease 20%, indeterminate colitis 22%, familial adenomatous polyposis
      9%). Incidence of anal stricture requiring intervention (11% overall) was
      significantly greater in HSAs than in SAs (16%vs 9%, P=0.02). Incidence of small
      bowel obstruction at any time postoperatively was 16%. Functional data were
      available for 234 patients. The median frequency of bowel actions during waking
      hours was significantly less in W pouches than in J pouches (four vs five,
      P=0.0005). CONCLUSION: A national web-based database has been developed for
      access by all Australasian colorectal units. Initial Australasian data compare
      favourably with other international studies. Pouchitis continues to be a long
      term problem. The leak rate and rate of late anal stricture requiring a procedure
      are higher if the anastomosis is handsewn rather than stapled. Functional results
      are better with the W pouch than with the J pouch.

PMID- 17223939
TI  - Results of a survey of the role of multidisciplinary team coordinators for
      colorectal cancer in England and Wales.
AB  - OBJECTIVE: Over the last 6 years, multidisciplinary teams (MDTs) have been
      established and play a key role in organizing the delivery of cancer care in the
      UK. There are no published data on the roles of their co-coordinators. To seek
      the views of colorectal multidisciplinary team co-ordinators (MDTCs) on what they
      do and how they do it. METHOD: Questionnaires were sent to the colorectal MDTC,
      or equivalent, in all 180 NHS hospital trusts in England and Wales where
      colorectal cancer surgery is performed. RESULTS: There was a 70% response rate.
      Seventy-one per cent of trusts now have a dedicated MDTC, whereas in 2002, only
      40% had one. MDTCs generally keep their information on databases, but these
      differ, and are not coordinated with data entry into the national colorectal
      cancer database of the Association of Coloproctology of Great Britain and
      Ireland. In only 26 trusts does the MDTC communicate decisions to primary care,
      and the patients seem almost completely excluded from this process. CONCLUSION:
      The recently formed national MDTC Forum should grasp the opportunity of
      coordinating all of this well-intentioned but pluralistic activity to the benefit
      of patients, primary care and hospital teams. An effective MDTC with a robust
      database will be the key in achieving cancer waiting time targets with useful
      audit, thereby improving patient care.

PMID- 17223940
TI  - Late results of treatment of anal fistulas.
AB  - OBJECTIVE: The aim of this paper was to analyse the results of treatment of anal
      fistulas retrospectively. METHODS: Between 1992 and 2004, 407 patients were
      operated on for perianal fistula. In the follow-up period, 107 patients were
      lost, so 300 patients were analysed in the study. The mean follow-up time was 4.2
      years. Analysed parameters included: types of surgical procedures in different
      kinds of fistulas and postoperative complications. Various types of surgical
      procedures and their effectiveness were described. Late results were assessed
      taking into account healing time, duration of sick leave, recurrence rate and
      incidence of anal sphincter dysfunction. Severity of gas and stool incontinence
      was assessed according to the Cleveland Clinic Incontinence Score. RESULTS: In
      our study, subcutaneous fistula was diagnosed in 23.3%, inter-sphincteric in 18%,
      trans-sphincteric in 37.7%, supra-sphincteric in 16% and extra-sphincteric in 5%
      of patients. Single-tract fistulas were present in 88.7% and multi-tract fistulas
      were present in 11.3%. Overall, 242 patients had primary fistulas and 58 patients
      had recurrent fistulas. The most frequently performed procedures were cutting
      seton (139 patients) and radical fistulectomy (104 patients). Recurrent fistulas
      developed in 14.3%. Postoperative gas and/or stool incontinence was noticed in
      10.7%. The recurrence rate was 5.4% in patients with primary fistula and in 51.7%
      patients presenting with a recurrent fistula. Gas and stool incontinence
      developed in 3.7% of patients with primary fistulas and in 39.7% of patients
      presenting with recurrent fistulas. Recurrence rate was 12% in the patients of
      single-tract fistulas and 32.4% in the patients of multi-tract fistulas.
      Postoperative gas and/or stool incontinence occurred in 8.3% of patients of
      single-tract fistulas and in 29.4% of patients of multi-tract fistulas.
      CONCLUSIONS: The complication rate was 10-fold higher in patients presenting with
      a recurrent fistula than in those with primary fistulas and threefold higher in
      patients with multi-tract fistulas than in those with single-tract fistulas.

PMID- 17223941
TI  - A novel procedure to assess anismus using three-dimensional dynamic anal
      ultrasonography.
AB  - OBJECTIVE: This study aimed to determine the value of three-dimensional (3D)
      dynamic endosonography in the assessment of anismus. METHOD: Sixty-one women
      submitted to anorectal manometry were enrolled including 40 healthy women and 21
      patients with anismus diagnosed by manometry. Patients were submitted to 3D
      endosonography. Images were acquired at rest and during straining and analysed in
      axial and midline longitudinal planes. Sphincter integrity was quantified. The
      angle between the internal edge of the puborectalis with a vertical line
      according to the anal canal axis was calculated at rest and during straining.
      RESULTS: The angle increased in 39 of the 40 normal individuals and decreased in
      all patients with anismus during straining compared with the angle at rest (88.36
      degrees ) and straining (98.65 degrees ) in normal individuals. In the anismus
      group, the angle decreased at rest (90.91 degrees ) and straining (84.89 degrees
      ). The difference between angle sizes in normal and anismus patients during
      straining was statistically significant (P < 0.5). CONCLUSION: Three-dimensional
      endosonography is a useful method to assess patients with anismus confirming the
      anorectal manometric results.

PMID- 17223942
TI  - Abdominal aortic aneurysm repair and colonic infarction: a risk factor appraisal.
AB  - OBJECTIVE: Colonic infarction is a recognized complication of abdominal aortic
      aneurysm (AAA) surgery. The clinical difficulty in establishing the diagnosis
      combined with the patient's poor physiological status is usually associated with
      a fatal outcome. We assessed our experience with this problem to identify a
      possible risk factor profile for these patients. METHOD: Patients records were
      identified from the operative logs, intensive care unit, Hospital Inpatient
      Enquiry system and vascular unit databases over a 6-year period. RESULTS: A total
      of 405 patients underwent AAA repair during this period; 140 as emergency
      ruptures. Nine patients were identified from the databases with known colonic
      infarction (2.2%). One was a woman. The mean age was 70 years. Seven patients had
      emergency ruptures (5%). Twenty independent risk factors were analysed using
      univariate and multivariate logistic regression models. Significant risk factors
      identified by using a multivariate analysis included the nature of the presenting
      patient, preoperative hypotension, prolonged cross-clamp time, intra-operative
      ischaemia and postoperative acidosis. Confirmatory diagnosis was made by
      colonoscopy in eight patients. One patient survived following the salvage
      surgery. The mean duration of survival was 10.5 days. The overall mortality was
      89% of patients. CONCLUSION: In our unit infrarenal AAA repair has a 2.2% rate of
      colonic infarction. A definitive diagnosis is best made by colonoscopy. A risk
      factor profile for the development of colonic infarction may be constructed on
      the basis of specific clinical parameters. Earlier intervention on the basis of
      this profile may ultimately reduce the current excessive mortality.

PMID- 17223944
TI  - Management of duodenal involvement in locally advanced colonic carcinoma.
AB  - Removal of locally advanced right-sided colonic carcinoma involving the duodenum
      can be challenging. There are few data on the optimal surgical approach. Adjacent
      organ involvement is associated with a poor prognosis and may be classified as
      inoperable with patients having palliative bypass procedures rather than primary
      resection. Survival is however improved after en bloc resection of adjoining
      viscera compared with intestinal bypass. We present a variety of surgical options
      depending on the extent of local invasion and the debility of the patient.

PMID- 17223943
TI  - Risk factors for severity and relapse of pseudomembranous colitis in an elderly
      population.
AB  - OBJECTIVE: Pseudomembranous colitis (PMC) is well recognized as an important
      cause of diarrhoea in patients receiving antibiotics, with significant
      consequences of morbidity and mortality. Mortality among elderly patients is
      high, and even with successful treatment, a significant number of patients
      relapse. To evaluate the outcome of elderly patients with PMC, and to try to
      identify risk factors that might influence mortality or relapse. METHOD: We
      studied 72 consecutive hospitalized patients with endoscopically proven PMC. The
      medical records of all patients with their clinical history and laboratory data
      were reviewed in detail. These data included: pre-hospitalization residence and
      physical status, background medical history, presenting symptoms, antibiotic
      history, haematological and biochemical parameters, treatment, duration of
      hospitalization, complications, mortality within 30 days of hospitalization and
      relapse. RESULTS: Of the 72 patients (M/F=34/38, mean age=77 years), 47% were
      nursing home residents. Prior to hospitalization, 91.6% of patients had received
      antibiotic treatment (cephalosporins - 64%, penicillins - 42% and quinolones -
      28%), 26% of patients received antacid therapy and 36% had been fed with a
      nasogastric tube (NGT). Thirty-seven (51%) patients recovered without
      complications, 21 (29%) patients died within 30 days of hospitalization and 14
      (19%) patients were re-hospitalized because of relapse of PMC. Multivariate
      analysis revealed that white blood cell count above 20 x 10(3)/mm3 (P=0.009),
      serum albumin level of less than 2.5 g/dl (P=0.02), and pre-hospitalization NGT
      feeding (P=0.01) were associated with high mortality. Treatment with acid
      reducing drugs (P=0.01) and living at a nursing home (P=0.06) were associated
      with high relapse rates. CONCLUSION: Pseudomembranous colitis is an important
      complication of antibiotic therapy and is associated with high mortality and
      recurrence rate, especially in old and debilitated persons. Pre-admission NGT
      feeding, severe leucocytosis and hypoalbuminaemia on admission are associated
      with increased mortality. Pre-hospitalization acid reducing treatment and nursing
      home residency are associated with increased risk of recurrence.

PMID- 17223948
TI  - Disclosure of information in English case law.

PMID- 17223949
TI  - High-grade lymphoma of the ileoanal pouch in an HIV-positive patient.

PMID- 17223959
TI  - Translational mini-review series on Toll-like receptors: networks regulated by
      Toll-like receptors mediate innate and adaptive immunity.
AB  - The Toll-like receptor (TLR) family provide key components of mammalian immunity
      and are part of the earliest surveillance mechanisms responding to infection.
      Their activation triggers the innate immune response, and is crucial to the
      successful induction of Th1/Th2-phenotyped adaptive immunity. Innate immunity was
      long considered to be non-specific and somewhat simple compared to adaptive
      immunity, mediated via the engulfment and lysis of microbial pathogens by
      phagocytic cells such as macrophages and neutrophils, and involving no complex
      protein-protein interactions. The emergence of the TLR field has contributed to a
      revision of our understanding, and innate immunity is now viewed as a highly
      complex process, in line with adaptive immunity. This review will give a brief
      overview of our current knowledge of TLR biology, and will focus on TLRs as key
      components in complex networks that activate, integrate and select the
      appropriate innate and adaptive immune responses in the face of immunological
      danger.

PMID- 17223960
TI  - Translational mini-review series on Toll-like receptors: Toll-like receptor
      ligands as novel pharmaceuticals for allergic disorders.
AB  - Characterization of the Toll-like receptor (TLR) family and associated signalling
      pathways provides a key molecular basis for our understanding of the relationship
      between exposure to microbial products and susceptibility to immune-mediated
      disorders. Indeed, ligation of TLR controls innate and adaptive immune responses
      by inducing synthesis of pro- as well as anti-inflammatory cytokines and
      activation of effector as well as regulatory lymphocytes. TLRs are therefore
      considered as major targets for the development of vaccine adjuvants, but also of
      new immunotherapies. Herein, we review the potential of TLR ligands as a novel
      class of pharmaceuticals for the prevention or treatment of allergic disorders.

PMID- 17223961
TI  - Translational mini-review series on Toll-like receptors: recent advances in
      understanding the role of Toll-like receptors in anti-viral immunity.
AB  - (TLRs) respond to pathogens to initiate the innate immune response and direct
      adaptive immunity, and evidence to date suggests that they have a role in the
      detection of viruses. Many viral macromolecules have been shown to activate anti
      viral signalling pathways via TLRs, leading to the induction of cytokines and
      interferons, while viruses also have means of not only evading detection by TLRs,
      but also of subverting these receptors for their own purposes. This review
      discusses the role of TLRs in the context of other known viral detection systems,
      and examines some of the often surprising results from studies using mice
      deficient in TLRs and their adaptors, in an attempt to unravel the particular
      contribution of TLRs to anti-viral immunity.

PMID- 17223962
TI  - Chronic inflammation: importance of NOD2 and NALP3 in interleukin-1beta
      generation.
AB  - Inflammation is part of the non-specific immune response that occurs in reaction
      to any type of bodily injury. In some disorders, the inflammatory process - which
      under normal conditions is self-limiting - becomes continuous and chronic
      inflammatory diseases might develop subsequently. Pattern recognition molecules
      (PRMs) represent a diverse collection of molecules responsible for sensing danger
      signals, and together with other immune components they are involved in the first
      line of defence. NALP3 and NOD2, which belong to a cytosolic subgroup of PRMs,
      dubbed Nod-like-receptors (NLRs), have been associated recently with inflammatory
      diseases, specifically Crohn's disease and Blau syndrome (NOD2) and familial cold
      autoinflammatory syndrome, Muckle-Wells syndrome and chronic infantile
      neurological cutaneous and articular syndrome (NALP3). The exact effects of the
      defective proteins are not fully understood, but activation of nuclear factor
      (NF)-kappaB, transcription, production and secretion of interleukin (IL)-1beta
      and activation of the inflammasome are some of the processes that might hold
      clues, and the present review will provide a thorough update in this area.

PMID- 17223963
TI  - Elevated levels of soluble non-classical major histocompatibility class I
      molecule human leucocyte antigen (HLA)-G in the blood of HIV-infected patients
      with or without visceral leishmaniasis.
AB  - The non-classical class I major histocompatibility complex molecules human
      leucocyte antigen (HLA)-G have been shown to play a role in HIV persistence, but
      no data are available on the expression of the soluble forms HLA-G5 and sHLA-G1
      in HIV-infected patients with and without opportunistic infections. The soluble
      HLA-G isoform was measured with an enzyme-linked immunosorbent assay (ELISA)
      method in plasma from 94 subjects: 31 HIV-1-seropositive, 17 with visceral
      leishmaniasis (VL), seven with both VL and HIV-1 infection and 39 healthy HIV
      seronegative subjects. Between groups, the frequency of sHLA-G positivity was
      statistically different: 81% of HIV-infected patients were positive, as were 57%
      of HIV-Leishmania infantum co-infected patients, 35% of HIV-seronegative patients
      with VL and 3% of healthy controls. Levels of the soluble forms of the
      immunomodulatory molecules HLA-G are elevated during HIV infection. In HIV
      Leishmania co-infected patients, sHLA-G secretion could contribute to the
      tolerogenic environment and to Leishmania immune evasion.

PMID- 17223964
TI  - Hepatitis C virus productive infection in mononuclear cells from patients with
      cryoglobulinaemia.
AB  - The relationship between the occurrence of cryoglobulins and hepatitis C virus
      (HCV) productive infection in peripheral blood and bone marrow-derived
      lymphocytes was explored. HCV minus strand RNA, the viral replicative
      intermediate, was searched for by a polyA(+) tract strand-specific Tth-based
      reverse transcriptase-polymerase chain reaction (RT-PCR) in lymphoid cells of 46
      patients with acute and chronic infection. The HCV minus strand was demonstrated
      in RNA extracted from six (13%) and five (11%) peripheral blood and bone marrow
      derived lymphocytes, respectively. The HCV replicating form in lymphoid cells was
      associated strictly with mixed cryoglobulinaemia (MCG), in that it was found in
      six of 13 (46%) MCG patients, including two with B cell non-Hodgkin's lymphoma
      (NHL). No traces of HCV-negative strand RNA were found in four patients with
      acute hepatitis C, in 15 with chronic active hepatitis without extrahepatic
      disorders, in seven with monoclonal gammopathy of undetermined significance, and
      in seven with B-NHL without MCG. These results emphasize the direct role of the
      virus in the pathogenesis of MCG and support the contention that HCV is not
      specifically lymphotropic, its entry and replication in lymphoid cells being
      determined largely by selective interactions.

PMID- 17223965
TI  - T and B lymphocyte subpopulations and activation/differentiation markers in
      patients with selective IgA deficiency.
AB  - Selective deficiency of immunoglobulin A (IgAD) and common variable
      immunodeficiency (CVID) are genetically closely related diseases, both of unknown
      pathogenesis. A plethora of abnormalities in lymphocyte subpopulations and
      expression of activation markers were repeatedly documented in CVID patients,
      while almost no data are available about lymphocyte subpopulations in IgAD
      patients. We determined basic lymphocyte subpopulations and those subpopulations
      that were reported to be abnormal in CVID patients (CD25, human leucocyte antigen
      (HLA)-DR CD45RA, CD45RO, CD27, CD28 and CD29 on both CD4(+) and CD8(+) cells,
      CD57 and CD38 on CD8(+) cells, CD21, CD27, IgM, IgD on B lymphocytes) in 85
      patients with IgAD, 47 patients with CVID and in 65 healthy controls. Statistical
      analysis was performed by the Mann-Whitney U-test; significant P-values were
      determined by means of Bonferoni's correction. Our results showed an increase in
      the relative number of CD8(+) cells and a decrease in the absolute number of
      CD4(+) cells compared to healthy people, but similar abnormalities in CVID
      patients were much more expressed. IgAD patients had significantly decreased
      expression of HLA-DR and increased expression of CD25 on CD4(+) lymphocytes, also
      CD29 expression was decreased on CD8(+) cells, while other
      activation/differentiation markers on T cells (including the expression of CD45RA
      and CD45RO antigens) were not changed. There were no statistically significant
      abnormalities in B lymphocyte developmental stages in IgAD patients compared to
      healthy controls. Our observation showed that the majority of T and B lymphocyte
      subpopulation abnormalities described previously in CVID are not present in IgAD
      patients.

PMID- 17223967
TI  - Autoimmunity and atherosclerosis: functional polymorphism of PTPN22 is associated
      with phenotypes related to the risk of atherosclerosis. The Cardiovascular Risk
      in Young Finns Study.
AB  - There is a growing body of evidence attesting the significance of inflammation in
      the pathogenesis of atherosclerosis. Protein tyrosine phosphate PTPN22 C/T single
      nucleotide polymorphism (SNP) at + 1858 has been identified recently as a
      susceptibility factor for various inflammatory autoimmune diseases. We
      hypothesized that data on the genetic polymorphism of the PTPN22 enzyme
      associated with an increased risk of autoimmunity could also provide insight into
      the possible role of autoimmunity in the pathogenesis of atherosclerosis.
      Therefore we analysed the PTPN22 + 1858 C/T polymorphism in a population of young
      Finnish adults (n = 2268) for whom data on carotid artery intima-media thickness
      (IMT), a presymptomatic predictor of atherosclerosis, and risk factors for
      atherosclerosis were available. In males carriage of the T allele of PTPN22 +
      1858 was associated significantly with IMT in univariate and multivariate
      analyses, while in females it was associated with several risk factors for
      atherosclerosis (BMI, waist circumference, waist-to-hip ratio, serum
      concentrations of C-reactive protein and triglycerides) but not with IMT. Our
      results indicate that the genetic polymorphism of PTPN22 + 1858 known to
      predispose to autoimmunity also enhances the development of atherosclerosis and
      thereby links the genetics of autoimmunity and atherosclerosis.

PMID- 17223966
TI  - Hyperactivity and reactivity of peripheral blood neutrophils in chronic
      periodontitis.
AB  - Some evidence exists that peripheral neutrophils from patients with chronic
      periodontitis generate higher levels of reactive oxygen species (ROS) after
      Fcgamma-receptor stimulation than those from healthy controls. We hypothesized
      that peripheral neutrophils in periodontitis also show both hyper-reactivity to
      plaque organisms and hyperactivity in terms of baseline, unstimulated generation
      and release of ROS. Peripheral neutrophils from chronic periodontitis patients
      and age/sex/smoking-matched healthy controls (18 pairs) were assayed for total
      ROS generation and extracellular ROS release, with and without stimulation
      (Fcgamma-receptor and Fusobacterium nucleatum), using luminol and isoluminol
      chemiluminescence. Assays were performed with and without priming with
      Escherichia coli lipopolysaccharide (LPS) and granulocyte-macrophage colony
      stimulating factor (GM-CSF). Phox gene expression (p22, p47, p67, gp91) was
      investigated using reverse transcription-polymerase chain reaction (RT-PCR).
      Neutrophils from patients produced higher mean levels of ROS in all assays. Total
      generation and extracellular release of ROS by patients' cells were significantly
      greater than those from controls after FcgammaR-stimulation, with (P = 0.023) and
      without (P < or = 0.023) priming with GM-CSF. Differences in unstimulated total
      ROS generation were not significant. By contrast, patients' cells demonstrated
      greater baseline, extracellular ROS release than those from controls (P = 0.004).
      This difference was maintained after priming with LPS (P = 0.028) but not GM-CSF
      (P = 0.217). Phox gene expression was similar in patient and control cells at
      baseline and stimulation with F. nucleatum (3 h) consistently reduced gp91(PHOX)
      transcripts. Our data demonstrate that peripheral neutrophils from periodontitis
      patients exhibit hyper-reactivity following stimulation (Fcgamma-receptor and F.
      nucleatum) and hyperactivity in terms of excess ROS release in the absence of
      exogenous stimulation. This hyperactive/-reactive neutrophil phenotype is not
      associated with elevated phox gene expression.

PMID- 17223968
TI  - Expression of biomarkers of interferon type I in patients suffering from chronic
      diseases.
AB  - Interferons (IFNs) are used widely in the treatment of viral infections, tumours
      and neurological disorders. The aim of this study was to evaluate the endogenous
      expressions of various IFN-induced compounds [specifically: neopterin (NPT),
      beta2microglobulin (beta2mg) and 2-5 oligoadenylate synthetase (2-5 OAS)] in
      patients with various chronic diseases requiring treatment with IFN type I. The
      results showed that patients with such chronic diseases as hepatitis C virus
      associated type II mixed cryoglobulinaemia (MC), chronic hepatitis C (CHC) and
      relapsing-remitting multiple sclerosis (RRMS) are characterized by different
      activations of the IFN system. Furthermore, the interindividual variability in
      baseline levels of IFN-induced biomarkers was higher in patients with chronic
      diseases than in healthy individuals. When levels of the above biomarkers were
      measured 24 h after the first injection of IFN in patients with CHC or RRMS,
      significant increases in expression levels of IFN-induced compounds were recorded
      but, again, there is a broad range of variability in the degree of increase.
      Further, a significant inverse correlation between baseline levels of NPT,
      beta2mg and 2-5 OAS activity and their relative increases after IFN
      administration was found in patients with CHC or RRMS. Together, the results are
      consistent with the observation that there is considerable interindividual
      heterogeneity in the clinical response to IFNs, which suggests that host factors
      other than disease markers must be taken into account in order to manage and
      optimize the IFN therapy.

PMID- 17223969
TI  - Hepatitis B virus (HBV) antigen-pulsed monocyte-derived dendritic cells from HBV
      associated hepatocellular carcinoma patients significantly enhance specific T
      cell responses in vitro.
AB  - To investigate whether hepatitis B virus (HBV) antigen-pulsed monocyte-derived
      dendritic cells (MoDC) could mount a T cell response in hepatocellular carcinoma
      (HCC) patients associated with chronic HBV infection, peripheral blood
      mononuclear cells (PBMCs) from 36 HBV-associated HCC patients were induced into
      MoDC and pulsed with hepatitis B core antigen (HBcAg) and hepatitis B surface
      antigen (HBsAg), alone and in combination. Co-stimulatory molecules CD80, CD86
      and CD40, as well as human leucocyte antigens D-related (HLA-DR) were found to
      express at the highest level on MoDC pulsed with HBcAg or HBsAg + HBcAg, at a
      median level on MoDC pulsed with HBcAg or HBsAg alone, and at the lowest level on
      non-antigen-pulsed MoDC. Interleukin (IL)-10 and IL-12 cytokines were released by
      antigen-pulsed MoDC at increased levels in the order: no-antigen < HBsAg < HBcAg
      < HBcAg + HBsAg. MoDC pulsed with HBcAg or HBsAg + HBcAg also had the strongest
      ability to stimulate autologous T cell proliferation and intracellular interferon
      (IFN)-gamma production. HBcAg- or HBsAg + HBcAg-pulsed MoDC could also induce HBV
      core peptide-specific CD8(+) T cell proliferation determined by tetramer
      staining. In addition, the antigen-pulsed MoDC were found to have a stronger
      capacity to produce IL-12 and induce T cell response in vitro for patients with
      higher alanine transaminase (ALT) levels than those with lower ALT levels,
      indicating that antigen pulse could substantially reverse the impaired function
      of MoDC in primary HCC patients with active chronic hepatitis B. In conclusion,
      HBV antigen-pulsed MoDC from HCC patients with chronic hepatitis B could induce
      HBV-specific T cell response in vitro.

PMID- 17223970
TI  - Production of interleukin (IL)-5 and IL-10 accompanies T helper cell type 1 (Th1)
      cytokine responses to a major thyroid self-antigen, thyroglobulin, in health and
      autoimmune thyroid disease.
AB  - Tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma exert detrimental
      effects in organ-specific autoimmune disease, while both destructive and
      protective roles have been demonstrated for interleukin (IL)-10, IL-4 and IL-5.
      We examined the production of these cytokines by peripheral blood mononuclear
      cells (PBMC) from patients with Hashimoto's thyroiditis (HT), Graves' disease
      (GD) and healthy controls, upon exposure to a thyroid self-antigen, human
      thyroglobulin (Tg), in the presence of autologous serum. Initially, TNF-alpha and
      IL-2 were produced in all three groups, accompanied by IL-10. Release of IFN
      gamma, IL-4 and, notably, IL-5 ensued. Both patient groups exhibited increased
      TNF-alpha, IL-2, IFN-gamma and IL-10 responses, and PBMC from HT patients
      secreted lower amounts of IL-5 than male, but not female, controls. Enhanced TNF
      alpha production by HT cells also occurred in the presence of pooled normal sera,
      indicating a dependency on intrinsic cellular factors. Conversely, higher
      production of TNF-alpha and IL-5 occurred in the presence of autologous sera than
      in the presence of pooled normal sera in both patient groups, indicating a
      dependency on serum constituents. Complement appeared to promote the production
      of IL-2 and particularly IL-5, the levels of which were reduced by neutralization
      of complement by heat- or zymosan treatment. The production of IFN-gamma and IL-2
      of the three groups together correlated directly with the serum anti-Tg activity.
      Moreover, TNF-alpha, IFN-gamma, IL-5 and IL-10 responses were markedly inhibited
      by partial denaturation of Tg by boiling. We hypothesize that autoantibodies and
      complement may promote mixed Th1/Th2 cell cytokine responses by enhancing the
      uptake of autoantigens by antigen-presenting cells.

PMID- 17223971
TI  - Combined therapy of transcatheter hepatic arterial embolization with intratumoral
      dendritic cell infusion for hepatocellular carcinoma: clinical safety.
AB  - The curative treatments for hepatocellular carcinoma (HCC), including surgical
      resection and radiofrequency ablation (RFA), do not prevent tumour recurrence
      effectively. Dendritic cell (DC)-based immunotherapies are believed to contribute
      to the eradication of the residual and recurrent tumour cells. The current study
      was designed to assess the safety and bioactivity of DC infusion into tumour
      tissues following transcatheter hepatic arterial embolization (TAE) for patients
      with cirrhosis and HCC. Peripheral blood mononuclear cells (PBMCs) were
      differentiated into phenotypically confirmed DCs. Ten patients were administered
      autologous DCs through an arterial catheter during TAE treatment. Shortly
      thereafter, some HCC nodules were treated additionally to achieve the curative
      local therapeutic effects. There was no clinical or serological evidence of
      adverse events, including hepatic failure or autoimmune responses in any
      patients, in addition to those due to TAE. Following the infusion of (111)Indium
      labelled DCs, DCs were detectable inside and around the HCC nodules for up to 17
      days, and were associated with lymphocyte and monocyte infiltration.
      Interestingly, T lymphocyte responses were induced against peptides derived from
      the tumour antigens, Her-2/neu, MRP3, hTERT and AFP, 4 weeks after the infusion
      in some patients. The cumulative survival rates were not significantly changed by
      this strategy. These results demonstrate that transcatheter arterial DC infusion
      into tumour tissues following TAE treatment is feasible and safe for patients
      with cirrhosis and HCC. Furthermore, the antigen-non-specific, immature DC
      infusion may induce immune responses to unprimed tumour antigens, providing a
      plausible strategy to enhance tumour immunity.

PMID- 17223972
TI  - The European internet-based patient and research database for primary
      immunodeficiencies: results 2004-06.
AB  - Because primary immunodeficiencies (PID) are rare diseases, transnational studies
      are essential to maximize the scientific outcome and lead to improved diagnosis
      and therapy. Immunologists in Europe have united to determine the prevalence of
      PID in Europe and to establish and evaluate harmonized guidelines for the
      diagnosis and treatment of PID as well as to improve the awareness of PID in
      Europe. In order to achieve this aim we have developed an internet-based database
      for clinical and research data on patients with PID. This database forms the
      platform for studies of demographics, the development of new diagnostic and
      therapeutic strategies and the identification of novel disease-associated genes.
      The database is completely secure, while providing access to researchers via a
      standard browser using password and encrypted log-in sessions and conforms to all
      European and national ethics and data protection guidelines. So far 2386 patients
      have been documented by 35 documenting centres in 20 countries. Common variable
      immunodeficiency (CVID) is the most common entity, accounting for almost 30% of
      all entries. First statistical analyses on the quality of life of patients show
      the advantages of immunoglobulin replacement therapy, at the same time revealing
      a mean diagnostic delay of over 4 years. First studies on specific questions on
      selected PID are now under way. The platform of this database can be used for any
      type of medical condition.

PMID- 17223973
TI  - Proinflammatory cytokine synthesis by mucosal fibroblasts from mouse colitis is
      enhanced by interferon-gamma-mediated up-regulation of CD40 signalling.
AB  - Gut mesenchymal fibroblasts form complex phenotypical and functional populations.
      They participate actively in homeostatic maintenance of the extracellular matrix,
      epithelial barrier function, repair mechanisms and leucocyte migration. In
      inflammation, they become activated, change matrix expression and synthesize
      proinflammatory mediators. Subpopulations of mucosal fibroblasts express CD40 and
      the aim of this study was to define its role in their proinflammatory function.
      Stable primary fibroblast lines derived from normal mouse colon and inflamed
      colon from CD4(+) CD45RB(high)-transplanted SCID mice were used as models to
      explore the role of mucosal fibroblast CD40 in the inflammatory process.
      Phenotype correlated with in situ fibroblast phenotype in the tissues of origin.
      Lines from both sources co-expressed CD40 and Thy1.2 independently of alpha
      smooth muscle actin. A subpopulation of CD40(+) fibroblasts from normal colon
      expressed CD40 at high levels and expression was enhanced by interferon (IFN)
      gamma treatment, whereas all CD40(+) fibroblasts from colitis expressed at low
      levels and expression was unaffected by IFN-gamma treatment. Despite lower-level
      expression of CD40 by cells from colitis, they secreted constitutively
      interleukin (IL)-6 and C-C chemokine (CCL)2. Ligation of CD40 enhanced secretion
      of these mediators and induced secretion of CCL3. CD40 in cells from colitis was
      more responsive to ligation than CD40 on cells from normal tissue and this
      sensitivity was amplified selectively by the action of IFN-gamma. We conclude
      that the inflammatory milieu in colitis induces long-lasting changes in phenotype
      and proinflammatory function in colonic fibroblasts. In particular,
      proinflammatory signalling from fibroblast CD40 is amplified synergistically by
      the Th1 effector T cell cytokine, IFN-gamma.

PMID- 17223974
TI  - Rheumatoid factor induction in murine models of liver injury.
AB  - Alcoholic liver disease and hepatitis C are associated with the production of
      autoantibodies such as rheumatoid factors (RF), which bind to IgG and can aid in
      host defence, but are also associated with pathological conditions such as
      rheumatoid arthritis. Because little is known about the role of RF in liver
      disease, we characterized the RF production that either occurred spontaneously in
      response to alcohol consumption or was induced by injection of an Escherichia
      coli glycolipoprotein in C57Bl/6 mice. Whereas severe liver damage was induced by
      carbon tetrachloride (CCl(4)), minimal damage was caused by chronic alcohol
      consumption. Liver damage was monitored by measurements of serum alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST). Circulating RF was
      induced in response to chronic alcohol consumption; the latter probably involved
      Toll-like receptor ligation. In contrast, CCl(4)-induced damage was not
      associated with RF induction. However, concurrent treatment with an E. coli
      glycolipoprotein macromolecule that induced RF, protected against CCL(4)-induced
      liver damage as measured by a highly significant decrease (P = 0.008) at 4 weeks
      in AST and ALT. RF induced by E. coli glycolipoprotein correlated with
      'protection' from liver damage, indicating that the RF autoimmune response does
      not necessarily exacerbate liver disease.

PMID- 17223975
TI  - Immunological responses and protective immunity against tuberculosis conferred by
      vaccination of Balb/C mice with the attenuated Mycobacterium tuberculosis (phoP)
      SO2 strain.
AB  - The Mycobacterium tuberculosis phoP mutant strain SO2 has been shown previously
      to be more attenuated than Mycobacterium bovis bacillus Calmette-Guerin (BCG) and
      confers protective immunity against tuberculosis in mice and guinea pig models.
      In this study we have investigated the survival and immunological responses of
      Balb/c mice infected with the M. tuberculosis SO2 strain. All Balb/C mice
      survived intratracheal infection with M. tuberculosis SO2 strain under conditions
      where all the mice infected with the parental M. tuberculosis MT103 had died
      after 9 weeks. Infection of Balb/c mice with M. tuberculosis SO2 was associated
      with comparatively lower levels of interferon (IFN)-gamma, interleukin (IL)-4 and
      tumour necrosis factor (TNF)-alpha and higher levels of inducible nitric oxide
      synthase (iNOS) during the late stage of infection, when compared with M.
      tuberculosis MT103 infection. The delayed-type hypersensitivity (DTH) response
      against M. tuberculosis culture filtrates was similar in mice infected with
      either the M. tuberculosis phoP SO2 strain or M. tuberculosis MT103. The
      protective efficacy of M. tuberculosis SO2 was compared with M. bovis BCG when
      delivered subcutaneously to groups of Balb/C mice. Following intratracheal
      challenge with M. tuberculosis H37Rv, protection was generated by 60 days post
      challenge in mice vaccinated with either vaccine. At day 120 post-challenge the
      levels of protection were still significantly greater when compared with the non
      vaccinated control group. The levels of protection conferred by vaccination with
      M. tuberculosis SO2 or with M. bovis BCG were similar, as measured by granuloma
      coalescence and pneumonia in addition to growth reduction of M. tuberculosis
      H37Rv.

PMID- 17223976
TI  - The impact of interleukin-6 promoter -597/-572/-174genotype on interleukin-6
      production after lipopolysaccharide stimulation.
AB  - Interleukin (IL)-6 is a pleiotropic cytokine, produced by different cells. There
      is accumulating evidence that IL-6 promoter polymorphisms impact substantially on
      various diseases and we identified kidney transplant recipients carrying the IL-6
      GGG/GGG (-597/-572/-174)genotype to have superior graft survival. To prove a
      functional impact on gene expression, we analysed systematically IL-6 production
      in healthy individuals with respect to the IL-6 (-597/-572/-174)genotype. IL-6
      was determined in 100 healthy blood donors at protein and mRNA levels upon
      specific stimulation in monocytes and T lymphocytes under whole blood conditions.
      GGG/GGG individuals showed a lower IL-6 secretion upon lipopolysaccharide (LPS)
      stimulation versus all others (P = 0.039). This link was even stronger when (
      597) and (-174)GG genotypes were reanalysed separately (P = 0.008, P = 0.017).
      However, we found neither a difference at the mRNA level or percentage of CD14(+)
      cells nor after T cell stimulation. We found evidence for the IL-6 (-597/-572/
      174)genotype to affect IL-6 synthesis, i.e. lower levels of IL-6 protein upon LPS
      stimulation in GGG/GGG individuals. Further studies are needed in kidney
      transplant recipients to investigate the potential link between the GGG/GGG
      genotype and graft survival. In line with this, determination of the genetic risk
      profiles might be promising to improve the transplant outcome in the individual
      patient.

PMID- 17223977
TI  - Agonistic antibodies to Fas induce a breach in the endothelial lining of the
      liver and a breakdown in B cell tolerance.
AB  - Liver disease can be associated with a breakdown in self-tolerance and the
      production of autoantibodies such as rheumatoid factors (RF), which bind to IgG.
      Here we investigated whether primary, non-infectious liver damage was sufficient
      to induce autoantibody production. We established a model of targeted liver
      damage induced by weekly sublethal injections of pro-apoptotic anti-Fas (CD95)
      antibodies. Liver damage, monitored by measurements of serum alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) levels, was minimal 1
      week after anti-Fas injection. However, the sublethal Fas stimulation was
      sufficient to trigger significant haemorrhage in the liver, as assessed by Evans
      Blue dye leakage into the organ 5 h after anti-Fas antibody injection. We
      observed an induction of RF in response to the weekly injections of sublethal
      anti-Fas antibodies but not of isotype control antibodies, indicating a breakdown
      of self-tolerance induced by Fas engagement. RF induction was unlikely to be due
      to direct activation of B cells, as splenocytes stimulated with anti-Fas
      antibodies in vitro did not produce RF. These studies show that sublethal damage
      to the liver by Fas engagement leads to liver haemorrhage and is sufficient to
      trigger the breakdown of self-tolerance.

PMID- 17223978
TI  - The interleukin-10 inducing effect of transforming growth factor-beta on human
      naive CD4+ T cells from cord blood is restricted to the TH1 subset.
AB  - Transforming growth factor (TGF-beta) seems to play a role in the regulation of
      immune responses, mainly by its suppressive function towards cells of the immune
      system. However, both in mice and human, conflicting data are published on the
      capacity of TGF-beta to induce interleukin (IL)-10 secretion in both naive and
      skewed T cell populations. Our aim was to test the IL-10-inducing capacity of TGF
      beta in both naive and skewed cord blood mononuclear cells (CBMCs) and elucidate
      the mechanism by which TGF-beta exerts its effect. Therefore, naive CBMCs and
      CBMCs during skewing under T helper 1 (Th1) and Th2 polarizing conditions were
      stimulated with CD3 and/or CD28 in the presence or absence of TGF-beta.
      Proliferation, cytokine production and mRNA expression of transcription factors
      was measured. TGF-beta enhanced the IL-10 production in Th1 and naive cells only,
      and suppressed the T(H)1 phenotype as demonstrated in cytokine levels and T-box
      expression in T cells (T-bet) expression. Interestingly, forkhead box p3 (Foxp3)
      expression tended to increase in both Th1 and Th2 cells. These data indicate that
      TGF-beta can induce a regulatory phenotype in both naive and Th1-polarized cells
      derived from cord blood. The induction of IL-10 was not observed in Th2-polarized
      phenotype, indicating that TGF-beta might be especially of interest for
      immunomodulation in Th1 cells.

PMID- 17223979
TI  - Vitamin E down-modulates mitogen-activated protein kinases, nuclear factor-kappaB
      and inflammatory responses in lung epithelial cells.
AB  - The airway epithelium plays an active role in acute lung inflammation by
      producing chemotactic factors and by expressing cell adhesion molecules involved
      in the migration of leucocytes to extravascular spaces. We have reported
      previously that neutrophil migration to airways can be down-modulated by
      exogenously administered vitamin E (alpha-tocopherol). The mechanism for this
      effect is not well understood, however. The action of alpha-tocopherol was
      investigated in human alveolar type II and bronchial epithelial cells stimulated
      with tumour necrosis factor-alpha. Treatment of alveolar epithelial cells with
      alpha-tocopherol resulted in down-regulated cell surface expression of
      intercellular adhesion molecule-1 (ICAM-1). On bronchial epithelial cells, both
      ICAM-1 and vascular adhesion molecule-1 were decreased, leading to diminished
      adherence of leucocytes to the cells. The production of the neutrophil
      chemoattractant interleukin-8 was attenuated in both alveolar and bronchial
      cells. These effects were preceded by reduced activation of the mitogen-activated
      protein kinases (MAPK), extracellular signal-regulated kinase (ERK1/2) and p38,
      as well as down-regulation of nuclear factor-kappaB. Comparing the effects of
      alpha-tocopherol with that of specific inhibitors of MAPK and protein kinase C
      (PKC) revealed that effects appear to be partly independent of PKC inhibition.
      These results implicate the anti-inflammatory action of alpha-tocopherol in
      addition to its anti-oxidant properties.

PMID- 17223980
TI  - Mycobacterium bovis bacillus Calmette-Guerin (BCG) induces human CC- and CXC
      chemokines in vitro and in vivo.
AB  - Both CC- and CXC-chemokines are known to be potent leucocyte activators and
      chemoattractants and play important roles in inflammatory responses. However,
      chemokine response to bacillus Calmette-Guerin (BCG) infection remains
      incompletely defined. In this study, we investigated human CC- [macrophage
      derived chemokine (MDC), monocyte chemoattractant protein (MCP)-1, macrophage
      inflammatory protein (MIP)-1alpha and eosinophil chemoattractant activity
      (eotaxin)] and CXC-interferon-inducible protein (IP)-10 chemokine production in
      response to BCG stimulation. BCG efficiently induced all chemokines tested in the
      urine of four bladder cancer patients undergoing intravesical BCG immunotherapy.
      The peak urinary chemokine responses occurred generally between the fourth and
      sixth weekly treatment, except eotaxin, which was less predictable. To evaluate
      the effect of BCG on induction of chemokines in vitro, urothelial cell lines and
      peripheral blood mononuclear cells (PBMCs) were used. Although BCG induced no or
      marginal chemokines from urothelial SV-HUC-1, RT4 and T24 cells, BCG-derived
      cytokines [interleukin (IL)-1beta, interferon (IFN)-gamma and tumour necrosis
      factor (TNF)-alpha] induced all chemokines tested except eotaxin from these cell
      lines. BCG also efficiently induced all chemokines tested except eotaxin from
      PBMCs of both BCG-naive and BCG-vaccinated subjects. MCP-1 and MIP-1alpha emerged
      at 4-5 h post-BCG exposure (early chemokines); IP-10 elevated at day 1 and peaked
      at day 2 (intermediate chemokine); and MDC elevated at day 1 and peaked at day 7
      (late chemokine). This kinetic pattern was paralleled with that of BCG-induced
      cytokines [early: TNF-alpha; intermediate: IL-6 and IL-10; and late: IFN-gamma
      and granulocyte-macrophage colony-stimulating factor (GM-CSF)]. Taken together,
      these results indicate that BCG directly or indirectly induces human CC- and CXC
      chemokine production, which may represent one of the mechanisms by which BCG
      exerts its anti-tumour activity.

PMID- 17223982
TI  - Growth hormone assay standardization: an important clinical advance.

PMID- 17223983
TI  - Congenital adrenal hyperplasia and P450 oxidoreductase deficiency.
AB  - Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive
      disorders, which are usually due to inactivating mutations in single enzymes
      involved in adrenal steroid biosynthesis. The characteristics of the biochemical
      and clinical phenotype depend on the specific enzymatic defect. In 21-hydroxylase
      and 11beta-hydroxylase deficiency only adrenal steroidogenesis is affected,
      whereas a defect in 3beta-hydroxysteroid dehydrogenase or 17alpha-hydroxylase
      also involves gonadal steroid biosynthesis. Recently, mutations in the electron
      donor enzyme P450 oxidoreductase were identified as the cause of CAH with
      apparent combined 17alpha-hydroxylase and 21-hydroxylase deficiency, thereby
      illustrating the impact of redox regulation enzymes on steroidogenesis. P450
      oxidoreductase deficiency (ORD) has a complex phenotype including two unique
      features not observed in any other CAH variant, skeletal malformations and severe
      genital ambiguity in both sexes. Despite invariably low circulating androgens,
      females with ORD may present with virilized genitalia and mothers may suffer from
      virilization during pregnancy. This apparently contradictory finding may be
      explained by the existence of an alternative pathway in human androgen
      biosynthesis, with important implications for physiology and pathophysiology.
      This review discusses the biochemical and clinical presentation and the genetic
      and functional basis of the currently known CAH variants, with a specific focus
      on ORD.

PMID- 17223981
TI  - Innate-immunity cytokines induced by very small size proteoliposomes, a Neisseria
      derived immunological adjuvant.
AB  - Neisserial outer membrane proteins have been combined with monosialoganglioside
      GM3 to form very small size proteoliposomes (VSSP), a nanoparticulated
      formulation used as a cancer vaccine for the treatment of cancer patients with
      GM3-positive tumours. VSSP were shown to elicit anti-GM3 and anti-tumour immune
      responses. VSSP have also been shown to be an efficient adjuvant for tumour-cell
      and peptide-antigen vaccines in mice. In vitro studies showed that VSSP promote
      maturation of both murine and human dendritic cells, suggesting that VSSP could
      be used as efficient adjuvants. In order to study further the capacity of VSSP to
      elicit innate immune responses, human peripheral blood mononuclear cells and
      monocytes derived thereof were assessed for in vitro secretion of interleukin
      (IL)-10, IL-6, IL-12 and interferon (IFN)-gamma. VSSP most prominently induced
      the secretion of IL-6. IL-10 was secreted at a lower level. IL-12 p40 (but no
      p70) was also detected. IFN-gamma response was observed in 56% of the tested
      samples. Cytokine secretion was not related to lipopolysaccharide (LPS) content
      and involved Toll-like receptor 2 (TLR2)-mediated signal transduction. VSSP also
      induced DC maturation and a cytokine secretion pattern (high IL-6/low IL-10)
      which differs from that induced by LPS. The observed proinflammatory cytokine
      secretion pattern and the capacity of VSSP to drive DC maturation are examined in
      the light of the properties of other bacterial derivatives currently being user
      for immunotherapy purposes. Our results suggest that VSSP could be tested in
      clinical settings where T helper 1-type immune responses would be beneficial.

PMID- 17223984
TI  - Clinical assessment and molecular analysis of GnRHR and KAL1 genes in males with
      idiopathic hypogonadotrophic hypogonadism.
AB  - OBJECTIVE: The pathogenesis of idiopathic hypogonadotrophic hypogonadism (IHH) is
      mostly unclear. We characterized the clinical findings and molecular analysis of
      GnRHR and KAL1 genes in 26 Brazilian males with IHH with and without
      hyposmia/anosmia. Design Clinical assessment was performed for endocrine status,
      olfactory structure and function, renal lesion, and mirror movement. The
      diagnosis of Kallmann syndrome (KS) included HH and the clinical complaint of
      hyposmia/anosmia or decreased olfactory acuity obtained by the Smell
      Identification Test (SIT). We analysed GnRHR and KAL1 genes using the polymerase
      chain reaction (PCR) direct sequencing method. RESULTS: A variable degree of HH
      was observed, including various clinical abnormalities, such as cryptorchidism,
      hearing loss, strabismus, cleft lip/palate, high-arched palate, dental agenesis,
      psychiatric disorders, learning dysfunction, and bimanual synkinesia. Twenty-two
      out of 26 patients with IHH (85%) were classified as KS. Abnormalities of
      olfactory bulbs/sulci were observed in 79% of KS patients. One-third of KS
      patients had renal defects and 45.5% had a positive family history. GnRHR gene
      sequence analysis showed no mutations. KAL1 sequence analysis identified two
      novel missense mutations: c.1061A to G in exon 7 (N304S) and c.1583C to A in exon
      10 (S478X). We also observed a 14-bp deletion within exon 11 that caused a
      premature termination. According to the National Center for Biotechnology
      Information (NCBI)-Single Nucleotide Polymorphism (SNP) database, two previously
      described polymorphisms (rs808119 and rs809446) were detected. CONCLUSION: KAL1
      mutations accounted for 12% of KS patients. This low prevalence of KAL1 mutations
      indicates that other genes, such as the fibroblast growth factor receptor 1
      (FGFR1) gene or other as yet undiscovered genes, epigenetic events and/or
      environmental factors might be involved in the aetiology and phenotypic
      variability of KS.

PMID- 17223985
TI  - Treatment of hereditary angioneurotic oedema (HANE) with tibolone.
AB  - OBJECTIVE: Eight women, aged 25-58 years, with hereditary angioneurotic oedema
      (HANE) were treated with tibolone, a synthetic steroid exhibiting oestrogenic,
      androgenic and progestational activity. DESIGN: Pilot study. RESULTS: Tibolone at
      a dose of 2.5-7.5 mg/day significantly reduced the number and severity of attacks
      and the number of ampoules of C1-esterase inhibitor (C1-INH) needed for
      symptomatic therapy. The efficacy of tibolone was comparable to that of danazol,
      while the androgenic side-effects were considerably reduced. CONCLUSIONS:
      Tibolone may represent an alternative to danazol administration for the
      prophylaxis of HANE in women.

PMID- 17223986
TI  - Cortisol secretary pattern and glucocorticoid feedback sensitivity in women from
      a Mediterranean area: relationship with anthropometric characteristics, dietary
      intake and plasma fatty acid profile.
AB  - BACKGROUND: Chronic stress is associated with a dysfunctional hypothalamic
      pituitary-adrenal (HPA) axis consisting on disturbances on the cortisol response
      and lipid metabolism. OBJECTIVE: To evaluate the HPA axis activity in women from
      a Mediterranean area, comparing three different measurements: daily cortisol
      secretory variability, postprandial cortisol secretion and glucocorticoid
      feedback sensitivity. In addition, HPA axis disturbance is correlated with
      dietary habits and plasma fatty acid profiles. DESIGN: The participants were 41
      women born during the first 6 months of 1960 and living in a Mediterranean area
      (Murcia, Spain). They were of normal weight, with a waist circumference of 80.5
      +/- 9.3 cm. Their salivary cortisol levels, 7-day dietary record and plasma fatty
      acid profile were evaluated. Daily cortisol variability and postlunch cortisol
      secretion were recorded and a dexamethasone suppression test is performed in
      order to detect possible HPA disturbance. RESULTS: Both the methods used for HPA
      axis evaluation were positively correlated (r = 0.448, P = 0.004). Subjects with
      normal diurnal curves (high cortisol variability) showed significantly higher
      cortisol values in the morning and postprandial cortisol secretion than women
      with pathological curves (medium and low variability). Cortisol variability was
      inversely correlated with waist circumference (r = -0.312, P = 0.047), suggesting
      that a disturbed HPA axis response may lead to an android pattern of body fat
      distribution. Dietary fat and saturated fatty acid intake were lower in the high
      cortisol variability group, while monounsaturated fatty acid intake was higher (P
      < 0.05). No major differences were reported in plasma fatty acid profile.
      CONCLUSIONS: A disturbed HPA axis is associated with abdominal fat distribution
      and a higher content of fat and saturated fatty acids in the diet. Women who
      chose a dietary pattern closer to the Mediterranean diet, with high
      monounsaturated fatty acid intake, showed lower levels on HPA axis disturbance.

PMID- 17223987
TI  - The emergence of the cortisol circadian rhythm in monozygotic and dizygotic twin
      infants: the twin-pair synchrony.
AB  - OBJECTIVE: Studies on the influence of genetic factors on the ontogeny of
      cortisol circadian rhythm in infants are lacking. This study evaluated the
      influence of twinning and the heritability on the age of emergence of salivary
      cortisol rhythm. DESIGN AND SUBJECTS: A longitudinal study was performed using
      salivary samples obtained during morning and night, at 2, 4, 8, 12, 16, 20 and 24
      weeks of postnatal life in 34 infants, 10 monozygotic (MZ) and 7 dizygotic (DZ)
      twin pairs. Salivary cortisol was determined by radioimmunoassay (RIA). Zigosity
      was verified by DNA analysis of at least 13 short tandem repeat polymorphisms.
      Difference of the emergence of cortisol circadian rhythm, within each twin pair,
      the intraclass correlation coefficient and the heritability index (h(2)) were
      calculated. RESULTS: The mean (+/- SEM) age of emergence of salivary cortisol
      circadian rhythm was similar in MZ and DZ (7.8 +/- 1.0 vs 7.4 +/- 1.3 weeks).
      Seven pairs showed coincidence of the emergence of cortisol rhythm. Ten pairs
      were not coincident; among them the within-pair difference of emergence of
      salivary circadian rhythm was similar in both MZ and DZ groups. The intraclass
      correlation coefficients were rMZ = 0.60, P = 0.02; and rDZ = 0.65, P = 0.03,
      respectively. The heritability index (h(2)) was 0.21 (ns). CONCLUSIONS: Salivary
      circadian rhythm appeared at the same postnatal age in MZ and DZ twin infants.
      Although several physiological aspects might be involved, the heritability index,
      obtained in the present study, suggests less genetic than environmental impact on
      the age of the onset of the cortisol circadian rhythm. Our data also indicated
      that each twin-pair show synchrony because they probably shared prenatal and
      postnatal environmental synchronizers.

PMID- 17223988
TI  - A lesser postprandial suppression of plasma ghrelin in Prader-Willi syndrome is
      associated with low fasting and a blunted postprandial PYY response.
AB  - OBJECTIVE: Ghrelin and polipeptide YY (PYY) are involved in the regulation of
      food intake. We evaluated these two peptides and their possible relationship in
      adult patients with Prader-Willi syndrome (PWS). PATIENTS: Seven patients with
      PWS, 16 age-sex-BMI matched obese and 42 age-sex matched lean subjects. DESIGN
      AND MEASUREMENTS: Fasting plasma PYY and ghrelin levels were measured in all
      subjects and, postprandially until 6 h, in seven matched subjects of each group.
      RESULTS: Fasting ghrelin levels were higher in PWS than in the other two groups.
      Fasting PYY levels were lower in patients with PWS than in lean subjects but
      similar to those in obese subjects. The postprandial decrease in ghrelin
      concentrations was lower in PWS as compared to the other two groups and therefore
      the 6-h-postprandial area under the curve (AUC) for ghrelin was higher in PWS
      than in obese subjects. PYY response after the meal was blunted in patients with
      PWS, but not in the other two groups that showed a peak at 60 min The AUC for PYY
      was lower in PWS as compared to the other two groups. Fasting PYY levels
      correlated negatively with fasting ghrelin levels and with ghrelin AUC and they
      were the only predictor for ghrelin AUC (beta = -0.464, P = 0.034). The increase
      in PYY correlated negatively with the decrease in ghrelin at times 60 min and 120
      min in PWS. CONCLUSIONS: In PWS, the low decrease in postprandial ghrelin levels
      could be related to the low fasting PYY concentrations and their blunted
      postprandial response.

PMID- 17223990
TI  - Resistin gene polymorphisms and progression of glycaemia in southern Chinese: a 5
      year prospective study.
AB  - OBJECTIVE: Human resistin gene (RETN) polymorphisms have been found to be
      associated with type 2 diabetes (T2DM), insulin resistance and/or obesity. We
      evaluated, in a 5-year prospective study, whether RETN polymorphisms could
      predict the progression of glycaemia in southern Chinese. DESIGN AND PATIENTS: We
      conducted a systematic search for variants in RETN in 70 southern Chinese
      subjects. This was followed by the genotyping in 624 unrelated nondiabetic
      subjects of two polymorphisms, -420C-->G and +62G-->A, previously reported in
      cross-sectional studies to be associated with T2DM in Asians, to examine their
      relationship with the progression of glycaemia in this cohort. RESULTS: We
      identified 15 polymorphisms, including 2 novel but rare polymorphisms (-319G-->A
      and +63G-->C). Compared to subjects with the CC genotype, -420GG subjects had
      higher 2-h glucose (7.7 +/- 1.8 vs. 7.2 +/- 2.0 mmol/l, P = 0.011) and insulin
      (101.6 +/- 69.5 vs. 79.8 +/- 59.5 mU/l, P = 0.021) during an oral glucose
      tolerance test. Carriers of the +62A allele had higher body mass indices (25.3 +/
      4.0 vs. 24.5 +/- 3.6 kg/m(2) in GG, P = 0.02). The presence of the allele -420G
      (OR 2.15, 95% CI 1.28-3.60, P = 0.004) or +62A (OR1.86, 95% CI 1.08-3.21, P =
      0.025) predicted the progression of glycaemia at Year 5, after adjustment for
      sex, age or body mass index. The haplotype G-A also conferred a higher risk of
      progression in glycaemia (P = 0.002). CONCLUSION: Our study would support the
      role of the resistin gene in obesity, insulin resistance and progression of
      glycaemia in southern Chinese.

PMID- 17223989
TI  - Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR,
      MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia.
AB  - OBJECTIVE: Familial glucocorticoid deficiency type I (FGD1) is a rare form of
      primary adrenal insufficiency resulting from recessive mutations in the ACTH
      receptor (MC2R, MC2R). Individuals with this condition typically present in
      infancy or childhood with signs and symptoms of cortisol insufficiency, but
      disturbances in the renin-angiotensin system, aldosterone synthesis or sodium
      homeostasis are not a well-documented association of FGD1. As ACTH stimulation
      has been shown to stimulate aldosterone release in normal controls, and other
      causes of hyponatraemia can occur in children with cortisol deficiency, we
      investigated whether MC2R changes might be identified in children with primary
      adrenal failure who were being treated for mineralocorticoid insufficiency.
      DESIGN: Mutational analysis of MC2R by direct sequencing. PATIENTS: Children (n =
      22) who had been diagnosed with salt-losing forms of adrenal hypoplasia (19
      isolated cases, 3 familial), and who were negative for mutations in DAX1 (NR0B1)
      and SF1 (NR5A1). RESULTS: MC2R mutations were found in three individuals or
      kindred (I: homozygous S74I; II: novel compound heterozygous R146H/560delT; III:
      novel homozygous 579-581delTGT). These changes represent severely disruptive loss
      of-function mutations in this G-protein coupled receptor, including the first
      reported homozygous frameshift mutation. The apparent disturbances in sodium
      homeostasis were mild, manifest at times of stress (e.g. infection, salt
      restriction, heat), and likely resolved with time. CONCLUSIONS: MC2R mutations
      should be considered in children who have primary adrenal failure with apparent
      mild disturbances in renin-sodium homeostasis. These children may have been
      misdiagnosed as having salt-losing adrenal hypoplasia. Making this diagnosis has
      important implications for treatment, counselling and long-term prognosis.

PMID- 17223991
TI  - Association of metabolic syndrome with impaired heart rate recovery and low
      exercise capacity in young male adults.
AB  - BACKGROUND: Impaired heart rate recovery (HRR) is a powerful predictor of overall
      mortality. AIM: The aim of the present study is to assess HRR in young adult
      males with metabolic syndrome and to compare HRR with those of obese patients who
      do not meet the criteria for metabolic syndrome. PATIENTS AND METHODS: Sixty-four
      newly diagnosed and untreated young male subjects (24 +/- 3 years) with metabolic
      syndrome and 40 age and sex matched obese or overweight control subjects (ages 23
      +/- 3 years) were enrolled in the study. All subjects performed a symptom limited
      exercise stress test under the standard Bruce protocol. HRR was calculated in the
      first, second and third minutes of the recovery period. The relationship between
      metabolic syndrome and HRR was evaluated via logistic regression analysis and a P
      value < 0.05 was accepted as significant. RESULTS: Body mass index (BMI) was 38.6
      +/- 3.68 and 32.22 +/- 2.99 kg/m(2) in the study and control groups, respectively
      (P < 0.001). Total cholesterol, low-density lipoprotein (LDL) cholesterol,
      triglycerides, systolic and diastolic blood pressures and fasting glucose levels
      were significantly higher in the study group. HRR in the first minute of the
      recovery period and mean exercise capacity were significantly lower in the study
      group patients with metabolic syndrome (P < 0.001 and P = 0.012, respectively).
      CONCLUSION: We determined that HRR was impaired in young adult males with
      metabolic syndrome compared with obese ones who do not meet the criteria of
      metabolic syndrome. This decreased HRR may have prognostic value in the
      prediction of vascular events in patients with metabolic syndrome.

PMID- 17223992
TI  - Clinical characteristics of poorly differentiated thyroid carcinomas compared
      with those of classical papillary thyroid carcinomas.
AB  - OBJECTIVE: The aim of this study was to compare the clinical presentation and
      prognosis of poorly differentiated thyroid carcinoma (PDTC) with those of
      classical papillary thyroid carcinoma (PTC) to identify the appropriate surgical
      modalities for use in conjunction with radioactive iodide ((131)I) therapy and
      external radiotherapy for treating PDTC. DESIGN: Sixty-seven PDTC patients (mean
      age 50.3 +/- 18.1 years, range 14-82 years) underwent surgery at the Chang Gung
      Medical Centre (CGMC), Linkou. To compare clinical presentations and treatment
      outcomes, 134 age- and gender-matched patients with classical PTC were selected
      randomly from the patient database at CGMC. RESULTS: Of the 67 PDTC patients, 53
      underwent near-total thyroidectomy. Following surgery, 45 were administered
      (131)I for remnant ablation and treatment of distant metastatic disease. Forty
      one of the 67 (61.2%) patients with PDTC and 26/134 (19.4%) with classical PTC
      failed to achieve disease-free status. Twenty-four of the 67 (34.3%) PDTC
      patients eventually died of thyroid cancer after a mean follow-up of 5.9 +/- 0.6
      years. Age and TNM staging at surgery were significant indicators of PDTC patient
      survival and mortality. CONCLUSIONS: As the prognosis for PDTC patients is poorer
      than that for classical PTC patients, (131)I treatment following surgery is
      useful. To improve the survival rate, early diagnosis is crucial for PDTC.

PMID- 17223993
TI  - The alpha(1S) subunit of the L-type calcium channel is not a predisposition gene
      for thyrotoxic periodic paralysis.
AB  - OBJECTIVE: Thyrotoxic periodic paralysis (TTP) has been associated with genetic
      variations in the gene encoding the alpha 1 subunit of the L-type calcium channel
      (CACNA1S). Mutations in CACNA1S are known to account for the majority of cases of
      familial hypokalaemic periodic paralysis (HOKPP). In this study we have examined
      48 genetic polymorphisms in the CACNA1S gene and genotyped a tagging set of
      representative polymorphisms to determine the role of this gene in TPP. DESIGN
      AND PATIENTS: A genetic association study was carried out with 98 TPP patients
      and 162 male thyrotoxic controls. Among 47 polymorphisms evaluated for linkage
      disequilibrium (LD) and the spectrum of haplotypes in the Chinese population, 31
      were selected as tagging single-nucleotide polymorphisms (SNPs) for genotyping
      the whole sample. A new genotyping protocol was used to analyse an
      insertion/deletion (I/D) polymorphism. RESULTS: We studied the LD among 47
      polymorphisms in the CACNA1S gene, which comprised a set of high-density markers
      with an average of one SNP every 2 kb. Subsequently, 31 tagSNPs were genotyped
      for all the samples. The gene is composed of three LD blocks. With this block
      structure, we were confident that variations of the gene were comprehensively
      covered by the tagSNPs. No significant association was found between the
      polymorphisms and TPP. CONCLUSION: We established the LD structure of this
      calcium channel subunit gene (CACNA1S) for the first time. However, its genetic
      variations are not associated with TPP in Chinese patients.

PMID- 17223994
TI  - Effects of testosterone and nandrolone on cardiac function: a randomized, placebo
      controlled study.
AB  - BACKGROUND: Androgens have striking effects on skeletal muscle, but the effects
      on human cardiac muscle function are not well defined, neither has the role of
      metabolic activation (aromatization, 5alpha reduction) of testosterone on cardiac
      muscle been directly studied. OBJECTIVE: To assess the effects of testosterone
      and nandrolone, a non-amplifiable and non-aromatizable pure androgen, on cardiac
      muscle function in healthy young men. DESIGN: Double-blind, randomized, placebo
      controlled, three-arm parallel group clinical trial. SETTING: Ambulatory care
      research centre. PARTICIPANTS: Healthy young men randomized into three groups of
      10 men. INTERVENTION: Weekly intramuscular injections of testosterone (200 mg
      mixed esters), nandrolone (200 mg nandrolone decanoate) or matching (2 ml arachis
      oil vehicle) placebo for 4 weeks. MAIN OUTCOME MEASURES: Comprehensive measures
      of cardiac muscle function involving transthoracic cardiac echocardiography
      measuring myocardial tissue velocity, peak systolic strain and strain rates, and
      bioimpedance measurement of cardiac output and systematic vascular resistance.
      RESULTS: Left ventricular (LV) function (LV ejection fraction, LV modified TEI
      index), right ventricular (RV) function (ejection area, tricuspid annular
      systolic planar motion, RV modified TEI index) as well as cardiac afterload (mean
      arterial pressure, systemic vascular resistance) and overall cardiac
      contractility (stroke volume, cardiac output) were within age- and gender
      specific reference ranges and were not significantly (P < 0.05) altered by either
      androgen or placebo over 4 weeks of treatment. Minor changes remaining within
      normal range were observed solely within the testosterone group for: increased LV
      end-systolic diameter (30 +/- 7 vs. 33 +/- 5 mm, P = 0.04) and RV end-systolic
      area (12.8 +/- 1.3 vs. 14.6 +/- 3.3 cm(2), P = 0.04), reduced LV diastolic septal
      velocity (Em, 9.5 +/- 2.6 vs. 8.7 +/- 2.0 cm/s, P = 0.006), increased LV filling
      pressure (E/Em ratio, 7.1 +/- 1.6 vs. 8.3 +/- 1.8, P = 0.02) and shortened PR
      interval on the electrocardiogram (167 +/- 13 vs. 154 +/- 12, P = 0.03).
      CONCLUSION: Four weeks of treatment with testosterone or nandrolone had no
      beneficial or adverse effects compared with placebo on cardiac function in
      healthy young men.

PMID- 17223995
TI  - Association of serum fetuin-A with carotid arterial stiffness.
AB  - OBJECTIVE: Fetuin-A is a circulating glycoprotein which is well characterized as
      an inhibitor of ectopic calcification. Vascular calcification commonly found in
      chronic kidney disease (CKD) patients is a predictor of cardiovascular death.
      Recently, several groups have demonstrated that low fetuin-A levels are
      associated with mortality in uraemic patients, possibly through regulation of
      vascular calcification. However, the physiological significance of fetuin-A in
      atherosclerosis remains unknown, except in specific conditions, such as vascular
      calcification in CKD patients. The objective of this study was to investigate the
      association between serum fetuin-A levels and arterial stiffness, a functional
      property of atherosclerosis, in healthy subjects. PATIENTS AND MEASUREMENTS: The
      study subjects comprised 141 healthy subjects. We measured serum fetuin-A levels
      and stiffness parameter beta for the common carotid artery, which was assessed by
      ultrasound using a phase-locked echo-tracking system. RESULTS: Simple regression
      analyses indicated that serum fetuin-A levels were significantly correlated with
      stiffness parameter beta (r = 0.200, P = 0.018). Multiple regression analyses
      showed that, besides age, fetuin-A (beta = 0.166, P = 0.033) independently
      contribute to the stiffness parameter beta (R(2) = 0.310, P < 0.0001).
      CONCLUSIONS: Serum fetuin-A level is associated with carotid arterial stiffness,
      independent of known atherogenic factors in healthy subjects.

PMID- 17223996
TI  - The dexamethasone-suppressed corticotropin-releasing hormone stimulation test and
      the desmopressin test to distinguish Cushing's syndrome from pseudo-Cushing's
      states.
AB  - OBJECTIVE: Cushing's syndrome (CS), when fully expressed, is easily diagnosed.
      Mild cases, however, may require careful distinction from pseudo-Cushing's states
      as may occur in depression, alcoholism, polycystic ovary disease and visceral
      obesity. The aim of the present study is a reappraisal of the diagnostic accuracy
      of the two tests most commonly used to differentiate CS from pseudo-Cushing's:
      corticotropin-releasing hormone (CRH) stimulation after low dose dexamethasone
      administration and desmopressin stimulation. DESIGN: The study population
      comprised 32 patients with CS and 23 with pseudo-Cushing's evaluated
      retrospectively. METHODS: Urinary free cortisol (UFC), serum cortisol at midnight
      and after low dose dexamethasone (1 mg overnight and 2 mg over two days) were
      measured. Further, patients were tested with dexamethasone + CRH and desmopressin
      and the diagnostic performances of the two tests were compared in the entire
      series as well as in patients with mild hypercortisolism only (i.e. UFC < 690
      nmol/24 h). RESULTS: As expected, measurement of UFC, assessment of cortisol
      rhythmicity and inhibition after 1 mg/2 mg dexamethasone failed to clearly
      classify patients with pseudo-Cushing's. Administration of CRH following 2-mg
      dexamethasone achieved 100% sensitivity but 62.5% specificity. Conversely,
      desmopressin testing correctly classified all but two patients with pseudo
      Cushing's (90% specificity) with 81.5% sensitivity. Diagnostic accuracy was
      comparable in the subgroup with mild hypercortisolism (21 CS, all 23 pseudo
      Cushing's patients). Desmopressin offered an incremental diagnostic effectiveness
      of 35.8/million inhabitants compared with dexamethasone + CRH as a second-line
      test. CONCLUSIONS: Neither of the two tests guarantees absolute diagnostic
      accuracy. The specificity of dexamethasone + CRH is less brilliant than
      previously reported and appears to be inferior to desmopressin stimulation. The
      greatest diagnostic effectiveness results from the low-dose dexamethasone test
      combined with the desmopressin test. Skilful use of dynamic testing and balanced
      clinical judgement are necessary to distinguish between Cushing's syndrome and
      pseudo-Cushing's.

PMID- 17223998
TI  - Characterization of the IGF system in 15 patients with Alstrom syndrome.
AB  - BACKGROUND: Alstrom syndrome (ALMS) is a rare recessively inherited progressive
      disease (OMIM 203800). Among its diverse spectrum of clinical features are
      phenotypes associated with deficiencies of the GH/IGF-I axis, including short
      stature, obesity, insulin resistance, hypertriglyceridaemia and heart failure.
      PATIENTS AND MEASUREMENTS: To characterize the IGF system in ALMS, we evaluated a
      subset of 15 young adults with ALMS for hepatic, renal and thyroid function.
      Glycaemic and hormone measurements such as insulin, GH, FSH, LH, testosterone and
      17-beta-oestradiol were clinically assessed. In addition, we measured IGF-I, IGF
      II, IGF binding-protein-3 (IGFBP-3) and acid labile subunit (ALS - the subunits
      that constitute the main somatomedin complex in the circulation), and IGFBP-1 and
      IGFBP-2 (known to influence the bioavailability of the IGFs). RESULTS: A
      significantly lower height was observed in ALMS patients compared to age-matched
      controls. ALMS patients were clinically obese (by weight and body mass index
      (BMI) standards) and leptin levels correlated with BMI. Renal and hepatic
      dysfunction was implicated in some patients by increased values of blood urea
      nitrogen (BUN) and creatinine, and transaminases, respectively. One-third of the
      patients presented with fasting hyperglycaemia and 80% were hyperinsulinaemic.
      TSH was slightly increased in 20% of patients. Baseline FSH and LH in females
      were within the normal range, while half of the males had abnormally low
      testosterone values. Male patients with hypogonadism showed significantly lower
      testosterone, oestrogen and ALS levels. Baseline GH values were not found to be
      increased. ALS and IGFBP-1 were significantly reduced and IGFBP-2 was markedly
      increased in ALMS patients compared to age-matched controls. The IGFs and IGFBPs
      were not significantly different between males and females affected with ALMS. No
      significant association was observed between IGFs or IGFBPs levels and weight,
      height, BMI, glycaemia, hyperinsulinaemia and testosterone levels. However, we
      found a significant association of gamma-glutamyltransferase (GGT) with IGFBP-2.
      IGF-I levels were significantly associated with LH in female patients.
      CONCLUSIONS: In summary, the reduction of ALS and the increase of IGFBP-2 points
      to a growth hormone deficiency (GHD) condition in ALMS. However, further tests,
      including GH dynamics, are needed to determine whether, or to what degree
      disturbances in the GH/IGF axis contribute to the relatively short stature.

PMID- 17223997
TI  - Human growth hormone (GH1) gene polymorphism map in a normal-statured adult
      population.
AB  - OBJECTIVE: GH1 gene presents a complex map of single nucleotide polymorphisms
      (SNPs) in the entire promoter, coding and noncoding regions. The aim of the study
      was to establish the complete map of GH1 gene SNPs in our control normal
      population and to analyse its association with adult height. DESIGN, SUBJECTS AND
      MEASUREMENTS: A systematic GH1 gene analysis was designed in a control population
      of 307 adults of both sexes with height normally distributed within normal range
      for the same population: -2 standard deviation scores (SDS) to +2 SDS. An
      analysis was performed on individual and combined genotype associations with
      adult height. RESULTS: Twenty-five SNPs presented a frequency over 1%: 11 in the
      promoter (P1 to P11), three in the 5'UTR region (P12 to P14), one in exon 1
      (P15), three in intron 1 (P16 to P18), two in intron 2 (P19 and P20), two in exon
      4 (P21 and P22) and three in intron 4 (P23 to P25). Twenty-nine additional
      changes with frequencies under 1% were found in 29 subjects. P8, P19, P20 and P25
      had not been previously described. P6, P12, P17 and P25 accounted for 6.2% of the
      variation in adult height (P = 0.0007) in this population with genotypes A/G at
      P6, G/G at P6 and A/G at P12 decreasing height SDS (-0.063 +/- 0.031, -0.693 +/-
      0.350 and -0.489 +/- 0.265, Mean +/- SE) and genotypes A/T at P17 and T/G at P25
      increasing height SDS (+1.094 +/- 0.456 and +1.184 +/- 0.432). CONCLUSIONS: This
      study established the GH1 gene sequence variation map in a normal adult height
      control population confirming the high density of SNPs in a relatively small
      gene. Our study shows that the more frequent SNPs did not significantly
      contribute to height determination, while only one promoter and two intronic SNPs
      contributed significantly to it. Studies in larger populations will have to
      confirm the associations and in vitro functional studies will elucidate the
      mechanisms involved. Systematic GH1 gene analysis in patients with growth delay
      and suspected GH deficiency/insufficiency will clarify whether different SNP
      frequencies and/or the presence of different sequence changes may be associated
      with phenotypes in them.

PMID- 17223999
TI  - Primary testicular failure in Klinefelter's syndrome: the use of bivariate
      luteinizing hormone-testosterone reference charts.
AB  - BACKGROUND: The diagnosis of androgen deficiency is based on clinical features
      and confirmatory low serum testosterone levels. In early primary testicular
      failure, a rise in serum LH levels suggests inadequate androgen action for the
      individual's physiological requirements despite a serum testosterone level within
      the normal range. The combined evaluation of serum LH and testosterone levels in
      the evaluation of testicular failure has not been widely advocated. PATIENTS:
      Seven hundred and six healthy males and 39 patients with known primary
      hypogonadism due to Klinefelter's syndrome and SRY-positive 46,XX karyotypes were
      included in the study. DESIGN: Testosterone, oestradiol and LH serum
      concentrations were measured in all individuals. Based on the 706 healthy males
      two-dimensional bivariate LH-testosterone reference charts were constructed.
      RESULTS: Despite a median serum total and free testosterone and oestradiol levels
      being reduced (P < 0.001) and LH levels elevated (P < 0.001) in Klinefelter's
      syndrome and 46,XX-males, many subjects (69%) had total testosterone within the
      reference range. However, using the bivariate charts all subjects lay outside the
      97.5 percentile. CONCLUSION: Bivariate LH and testosterone charts are useful in
      the evaluation of men with known primary testicular failure due to sex
      chromosomal aneuploidy in whom evaluation based on testosterone measurement in
      isolation underestimates the prevalence of hypogonadism. It is, however,
      important to emphasize that isolated use of the bivariate evaluation should not
      form the basis for androgen substitution therapy. Further studies are needed in
      order to evaluate the use of bivariate LH and testosterone charts in the
      assessment of any younger man with possible primary testicular failure.

PMID- 17224001
TI  - Serum levels of adiponectin and IGFBP-1 in short children born small for
      gestational age.
AB  - OBJECTIVE: The aim of this study was to quantify serum adiponectin concentrations
      in short children born small for gestational age (SGA) compared with those in
      children born appropriate for gestational age (AGA), and to assess the
      relationship between the serum levels of adiponectin and insulin-like growth
      factor binding protein-1 (IGFBP-1) known as a predictor of the development of
      type 2 diabetes mellitus and cardiovascular disease. SUBJECTS AND METHODS:
      Sixteen prepubertal short children born SGA and 20 short children born AGA,
      matched for age, body mass index, height, pubertal status, gestational age, bone
      age and midparental height, were included in the study. The serum levels of
      adiponectin, IGFBP-1, insulin and insulin-like growth factor-I (IGF-I) were
      measured in the fasting state. RESULTS: The levels of serum adiponectin were
      significantly lower in the SGA than in AGA children (10.5 +/- 4.2 vs. 13.9 +/-
      5.1 micro g/ml, P < 0.05). The levels of serum IGFBP-1, insulin and IGF-I were
      all similar in both groups. Overall, there was a significant positive correlation
      between adiponectin and IGFBP-1 (r = 0.40, P < 0.05). CONCLUSIONS: Our results
      suggest that hypoadiponectinaemia in short SGA children without catch-up growth
      may reflect insulin resistance and imply a higher risk of developing type 2
      diabetes mellitus. Additionally, adiponectin may be a more sensitive indicator
      for latent insulin resistance than IGFBP-1 in short SGA children.

PMID- 17224000
TI  - Effects of rosiglitazone and metformin on inflammatory markers and adipokines:
      decrease in interleukin-18 is an independent factor for the improvement of
      homeostasis model assessment-beta in type 2 diabetes mellitus.
AB  - OBJECTIVE: We examined the individual pharmacological effects of the addition of
      rosiglitazone and metformin to glimepiride on inflammatory markers and adipokines
      in patients with type 2 diabetes mellitus. We analysed the relationships between
      these variables, the measurements of insulin sensitivity and beta-cell function
      in patients treated with rosiglitazone plus glimepiride. DESIGN AND PATIENTS: One
      hundred twenty (120) patients with type 2 diabetes mellitus were randomized and
      treated with glimepiride plus rosiglitazone or glimepiride plus metformin for 12
      weeks. The plasma concentrations of the inflammatory markers and adipokines were
      measured at baseline and after 12 weeks. MEASUREMENTS: Markers of insulin
      sensitivity and beta-cell function were determined by the quantitative insulin
      sensitivity check index (QUICKI) and the homeostasis model assessment of beta
      cell function (HOMA-beta), respectively. Plasma concentrations of adiponectin
      were measured by radioimmunoassay. Plasma concentrations of resistin, tumour
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-18 (IL
      18) were measured using ELISA. RESULTS: Improvements in fasting insulin level,
      QUICKI and HOMA-beta were noted in the rosiglitazone-treated group. Only the
      QUICKI value improved in the metformin-treated group. Adiponectin concentrations
      significantly increased in the rosiglitazone-treated group after 12 weeks.
      Significant decreases in resistin, C-reactive protein, TNF-alpha, IL-6 and IL-18
      were seen in the rosiglitazone-treated patients but not in the metformin-treated
      patients. The independent risk factor for the HOMA-beta change according to
      stepwise multivariate regression analysis was a change in IL-18. CONCLUSIONS:
      Rosiglitazone, but not metformin, improved the plasma concentrations of
      inflammatory markers and adipokines in patients with type 2 diabetes mellitus. A
      decrease in IL-18 is an independent factor for the improvement of HOMA-beta in
      type 2 diabetes mellitus.

PMID- 17224002
TI  - Acute and chronic neuroendocrine effects of interferon-beta 1a in multiple
      sclerosis.
AB  - OBJECTIVE: Treatment of multiple sclerosis with interferon-beta (IFN-beta)
      results in variable responses interindividually. Cytokine-hormone interactions
      may modulate the therapeutic effects of IFN-beta. Since hyperactivity of the
      hypothalamo-pituitary-adrenal (HPA) axis and other neuroendorine disturbances
      occur in multiple sclerosis, we determined the detailed neuroendocrine response
      of patients with multiple sclerosis to IFN-beta. DESIGN: Longitudinal open-label
      study. PATIENTS: Eight patients with relapsing-remitting multiple sclerosis (four
      women, age 31.9 +/- 1.5 years, EDSS 1.5-2.5). MEASUREMENTS: Plasma ACTH,
      cortisol, prolactin, GH, TSH, LH and FSH were determined in 30-min intervals
      during 8 h on four occasions: after intramuscular injection of saline; after the
      first dose of IFN-beta 1a; after the second IFN-beta dose with oral indomethacin
      pretreatment; and after 3 months of IFN-beta therapy. Dexamethasone-corticotropin
      releasing hormone test was performed before and at 3 months on IFN-beta. RESULTS:
      Compared to saline, IFN injection resulted in marked rise in plasma ACTH (mean,
      370% of baseline), cortisol (214%), prolactin (253%) and GH (756%), between 2 and
      6 h after injection. With indomethacin, hormone secretion occurred with reduced
      peak values. Endocrine response adapted partially after 3 months of treatment.
      HPA axis activity decreased in most patients, but increased in one patient with
      frequent relapses. CONCLUSIONS: Marked neuroendocrine effects occur in response
      to IFN-beta in multiple sclerosis. Upon prolonged treatment, these effects
      partially adapt, and HPA axis hyperactivity is reduced. Prospective studies to
      determine the relation to individual treatment response can be based on these
      findings.

PMID- 17224003
TI  - Central pulse wave velocity is responsible for increased brachial-ankle pulse
      wave velocity in subclinical hypothyroidism.
AB  - OBJECTIVE: Subclinical hypothyroidism affects 5-15% of the general population,
      and is associated with increased morbidity from cardiovascular disease. We
      recently reported a significant increase in brachial-ankle pulse wave velocity
      (baPWV), a parameter of arterial stiffening and an independent predictor for the
      presence of cardiovascular disease, in subclinical hypothyroidism. The current
      study was performed to assess which arterial segment is responsible for enhanced
      baPWV in subclinical hypothyroidism. PATIENTS AND METHODS: Central PWV (PWV in
      heart-femoral segments), peripheral PWV (PWV in femoral-ankle segments), and
      baPWV were measured in subclinical hypothyroid patients and normal subjects.
      RESULTS: Central PWV, baPWV, and peripheral PWV were significantly higher in
      subclinical hypothyroid patients than in normal subjects. BaPWV was significantly
      and positively correlated with central and peripheral PWV in both groups.
      However, a significant and positive correlation between central and peripheral
      PWV in normal subjects was not found in subclinical hypothyroid patients.
      Moreover, stepwise regression analysis showed that the association of central PWV
      with baPWV was stronger than that of peripheral PWV, whereas in normal subjects
      central PWV was not associated with baPWV. CONCLUSIONS: Our results demonstrate
      that central and peripheral PWV are significantly higher in subclinical
      hypothyroid patients, and that the increase in baPWV depends more strongly on
      central PWV than on peripheral PWV in these patients. This suggests that
      increased elastic arterial stiffening of the aorta, rather than of peripheral
      muscular arteries, might be more responsible for increased general arterial
      stiffening in subclinical hypothyroid patients.

PMID- 17224004
TI  - Spurious counts and spurious results on haematology analysers: a review. Part I:
      platelets.
AB  - The widespread use of haematology analysers (HA) has led to a major improvement
      of cellular haematology, because of quick and accurate results found in most
      instances. However, in several situations, spurious results are observed.
      Inadequate blood samples, situations induced by the anticoagulant(s) used,
      peculiar changes related to the pathology in the patient, and technical
      considerations about performances of the various HA must be considered. Spurious
      thrombocytopenia occurs in several circumstances related to the presence of
      ethylenediamine tetra-acetic acid (EDTA) used as the anticoagulant. Mechanism of
      EDTA-dependent platelet (PLT) agglutination is related to circulating
      (auto)antibodies directed against normally hidden epitope(s) in the glycoprotein
      alpha IIb/beta IIIa complex from PLT membrane exposed only in the presence of
      EDTA. Other spuriously low PLT counts may be related to EDTA, including PLT
      rosetting around white blood cells (WBC; satellitism) and PLT-WBC aggregates, but
      mechanisms responsible for those latter phenomena are less well known. Spurious
      increase of PLT count may be related to several situations, including fragmented
      red blood cells, cytoplasmic fragments of nucleated cells, cryoglobulins,
      bacteria or fungi, and lipids. Flags generated in several of these situations
      alert the operator on possible abnormal findings and may identify the problem.
      Analysing only PLT parameters is not sufficient: in many situations the WBC
      differential scattergram is of crucial help for flagging. Flags generated depend
      on the software version on the HA used, the performance in detecting the same
      anomalies may differ according to which analyser is used, even those from the
      same manufacturer. Operators must be aware of the characteristics of their
      analyser and be able to recognize and circumvent anomalous results.

PMID- 17224005
TI  - Spurious counts and spurious results on haematology analysers: a review. Part II:
      white blood cells, red blood cells, haemoglobin, red cell indices and
      reticulocytes.
AB  - Haematology analysers provide quick and accurate results in most situations.
      However, spurious results, related either to platelets (part I of this report) or
      to other parameters from the cell blood count (CBC) may be observed in several
      instances. Spuriously low white blood cell (WBC) counts may be observed because
      of agglutination in the presence of ethylenediamine tetra-acetic acid (EDTA).
      Cryoglobulins, lipids, insufficiently lysed red blood cells (RBC), erythroblasts
      and platelet aggregates are common situations increasing WBC counts. In most of
      these instances flagging and/or an abnormal WBC differential scattergram will
      alert the operator. Several situations lead to abnormal haemoglobin measurement
      or to abnormal RBC count, including lipids, agglutinins, cryoglobulins and
      elevated WBC counts. Mean (red) cell volume (MCV) may be also subject to spurious
      determination, because of agglutinins, excess of glucose or salts and
      technological considerations. In turn, abnormality related to one measured
      parameter will lead to abnormal calculated RBC indices: mean cell haemoglobin
      content (MCHC) is certainly the most important RBC indices to consider, as it is
      as important as flags generated by the haematology analysers (HA) in alerting the
      user to a spurious result. In many circumstances, several of the measured
      parameters from CBC may be altered, and the discovery of a spurious change on one
      parameter frequently means that the validity of other parameters should be
      considered. Sensitive flags now allow the identification of several spurious
      counts, but only the most sophisticated HA have optimal flagging and more simple
      HA, especially those without a WBC differential scattergram, do not possess the
      same sensitivity for detecting anomalous results. Reticulocytes are integrated
      now into the CBC in many HA, and several situations may lead to abnormal counts.

PMID- 17224006
TI  - Inaccuracy of high-performance liquid chromatography estimation of haemoglobin F
      in the presence of increased haemoglobin A1c.
AB  - Increasingly high-performance liquid chromatography is being used for
      identification and quantification of normal and variant haemoglobins. In many
      laboratories, the Beta Thal Short programme of the Bio-Rad Variant II instrument
      is used for this purpose. We noted that a factitious elevation of haemoglobin F
      was sometimes observed in diabetic patients and therefore carried out a
      systematic study of this phenomenon. We found discrepant results in 41% of
      samples from diabetic patients but in no normal volunteers. This factitious
      elevation could be predicted from a retention time for haemoglobin F of more than
      1.15 min, the normal retention time being 1.08-1.15 min. Haemoglobinopathy
      laboratories need to be alert to the possibility of this erroneous result.

PMID- 17224007
TI  - An improved method for the diagnostic approach of alpha+-thalassaemia.
AB  - An improved method for the diagnostic approach of alpha(+)-thalassaemia is
      described. The method is based on five common parameters: absence of iron
      deficiency, mild morphological abnormalities of erythrocytes, normal or slightly
      reduced erythrocytic indices MCV and MCH, normal chromatographic findings, and
      presence of haemoglobin H inclusions in erythrocytes with methyl-violet stain
      after, but not before, incubation with oxidant agent. We studied by DNA analysis,
      58 subjects fulfilling the above mentioned diagnostic criteria and we found that
      50 of them (86.2%) had a alpha-globin gene defect. In the remaining eight
      subjects (13.8%) no alpha-gene defect could be documented with the techniques
      used in the DNA analysis, which detect the six well-known alpha(+)-thalassaemic
      defects in the Greek population. We conclude that the improved method, we
      described has a high sensitivity and accuracy in the screening of alpha(+)
      thalassaemia.

PMID- 17224008
TI  - Expression of CD55 and CD59 on peripheral blood cells in patients with
      lymphoproliferative disease of granular lymphocytes.
AB  - Lymphoproliferative disease of granular lymphocytes (LDGL) is a disorder
      characterized by the clonal expansion of granular lymphocytes. It has recently
      been shown that the clonal expansion of granular lymphocytes occurs in patients
      with paroxysmal nocturnal hemoglobinuria (PNH) in a subclinical fashion. To test
      the possibility that LDGL patients share a PNH phenotype, we obtained peripheral
      blood cells from 20 patients with LDGL and examined the expression of the
      glycosylphosphatidyl inositol (GPI)-anchored proteins, CD55 and CD59. Compared
      with normal controls, however, a defective expression of CD55/59 was not observed
      on either granulocytes or erythrocytes from LDGL patients. An unexpected finding
      was the significantly lower CD55/59 expression on granular lymphocytes from
      patients with CD16(+)CD56(-) phenotype LDGL than from patients with
      CD16(+)CD56(+) phenotype LDGL, or natural killer (NK) and NK/T lymphocytes from
      healthy individuals. The positive correlation between the expression of CD56 and
      CD55/59 might have some relevance to the functional properties of the CD56(+)
      subset of large granular lymphocytes.

PMID- 17224009
TI  - Effect of a bone marrow microenvironment on the ex-vivo expansion of umbilical
      cord blood progenitor cells.
AB  - Progenitor cells (CD34(+)) can be isolated from umbilical cord blood and used to
      correct or reconstitute various cell lines within the haematopoietic and
      endothelial cell lineage. The main disadvantage of this procedure relates to the
      low volume of blood that can be collected after the umbilical cord has been
      clamped, which limits the number of progenitor cells available for treatment.
      This limitation, however, can be overcome by expanding CD34(+) cells ex vivo. Our
      aim was to perform a controlled study to determine if the ex-vivo proliferation
      of umbilical cord CD34(+) cells is enhanced when they are placed in a system that
      mimics the bone marrow microenvironment. For this purpose, CD34(+) cells were
      isolated from umbilical cord blood using a magnetic cell sorting kit and seeded
      in platforms containing different cocktails of cytokines with and without a three
      dimensional (3D) biomatrix. Results from this study suggest that the number of
      viable cells can double after 1 week in any of the culture platforms and that the
      3D biomatrix does not enhance cell proliferation.

PMID- 17224010
TI  - Acquired haemophilia masked by warfarin therapy.
AB  - Acquired haemophilia is a rare phenomenon and prompt diagnosis is essential for
      successful treatment. Early laboratory detection could minimize its potentially
      devastating consequences and reduce mortality but when a masking element such as
      anticoagulant therapy is present, delay in diagnosis is not uncommon. A prolonged
      activated partial thromboplastin time (APTT) may be falsely attributed to
      warfarin alone, particularly when it is associated with oral anticoagulant
      overdose. We describe two patients on treatment with warfarin who presented with
      a bleeding diathesis and disproportionately prolonged APTT, which led to the
      diagnosis of antibodies directed against factor VIII.

PMID- 17224011
TI  - The Diamed assay has a poor positive predictive value for HIT in a tertiary
      hospital referral setting.

PMID- 17224012
TI  - The investigation of JAK2 mutation in Chinese myeloproliferative diseases
      identification of a novel C616Y point mutation in a PV patient.

PMID- 17224013
TI  - Current haematological findings in cobalamin deficiency.

PMID- 17224016
TI  - Morphogenesis of the peri-implant mucosa: an experimental study in dogs.
AB  - PURPOSE: The objective of the present experiment was to study the morphogenesis
      of the mucosal attachment to implants made of c.p. titanium. MATERIAL AND
      METHODS: All mandibular premolars were extracted in 20 Labrador dogs. After a
      healing period of 3 months, four implants (ITI Dental Implant System) were placed
      in the right and left sides of the mandible. A non-submerged implant installation
      technique was used and the mucosal tissues were secured to the conical marginal
      portion of the implants with interrupted sutures. The sutures were removed after
      2 weeks and a plaque control program including daily cleaning of the remaining
      teeth and the implants was initiated. The animals were sacrificed and biopsies
      were obtained at various intervals to provide healing periods extending from Day
      0 (2 h) to 12 weeks. The mandibles were removed and placed in the fixative. The
      implant sites were dissected using a diamond saw and processed for histological
      analysis. RESULTS: Large numbers of neutrophils infiltrated and degraded the
      coagulum that occupied the compartment between the mucosa and the implant during
      the initial phase of healing. At 2 weeks after surgery, fibroblasts were the
      dominating cell population in the connective tissue interface but at 4 weeks the
      density of fibroblasts had decreased. Furthermore, the first signs of epithelial
      proliferation were observed in specimens representing 1-2 weeks of healing and a
      mature barrier epithelium occurred after 6-8 weeks of healing. The collagen
      fibers of the mucosa were organized after 4-6 weeks of healing. CONCLUSION: It is
      suggested that the soft-tissue attachment to implants placed using a non
      submerged installation procedure is properly established after several weeks
      following surgery.

PMID- 17224017
TI  - Effect of stress on information processing in the dental implant surgery setting.
AB  - OBJECTIVES: Dental implantation is a stressful experience, both physically and
      psychologically. The effect of anxiety on the patient's ability to process
      relevant information prior to a stressful clinical situation (implant insertion)
      was evaluated. MATERIALS AND METHODS: The study included 98 healthy patients,
      scheduled for implant insertion. Two different audio-tapes with relevant
      information regarding implant insertion were listened to immediately pre
      operatively. Recognition questionnaires, consisting of 21 statements (correct and
      false information) were prepared, one for each tape. The dental anxiety scale
      (DAS), degree of state anxiety (SA), evaluation of pain expected during surgery,
      and extent to which patients understood the information provided were examined on
      100 mm visual analogue scales. RESULTS: A significant positive correlation was
      found between patients' DAS and SA and between patients' expectation to
      experience pain during the surgical procedure. Certainty of understanding (CU)
      significantly contributed to the explanation of correctly classified statements
      (beta=-0.43, t=3.71, P<0.01). CU was positively related to SA and negatively to
      DAS. CONCLUSIONS: In a stressful pre-surgical situation, the ability to process
      relevant information may be severely impaired and should not be given to patients
      immediately before planned treatment.

PMID- 17224018
TI  - Immediate loading of dental implants placed in severely resorbed edentulous
      mandibles reconstructed with autogenous calvarial grafts.
AB  - OBJECTIVE: The aim of this prospective study was to present the clinical outcome
      of immediately loaded dental implants placed in edentulous, severely atrophied
      mandibles, after reconstruction with autogenous multilayered calvarial grafts.
      MATERIALS AND METHODS: Six patients, two males and four females, aged 40-67 years
      (mean: 56 years) presenting with severely atrophied edentulous mandibles (Cawood
      and Howell class VI), were reconstructed with multilayered calvarial bone grafts
      placed in the intraforaminal area of the mandible. Five to 8 months afterwards,
      23 dental implants were placed in the reconstructed areas (three to four implants
      per patient) and immediately loaded with implant-supported overdentures. Patients
      were followed with clinical and radiographic controls annually. RESULTS: Recovery
      after the reconstruction was uneventful in all patients. All 23 implants were
      osseointegrated 1-3 years after the start of immediate loading. The survival and
      success rates of implants were 100% and 95.7%, respectively. CONCLUSION: Results
      from this study showed that immediate loading of dental implants placed in
      severely atrophied edentulous mandibles reconstructed with calvarial bone grafts
      is a predictable procedure, which permits a successful dental rehabilitation with
      a shortening of treatment times.

PMID- 17224019
TI  - Profiling of bacterial flora in crevices around titanium orthodontic anchor
      plates.
AB  - OBJECTIVES: The aims of this study were to characterize the microflora in
      crevices around titanium orthodontic anchor plates using anaerobic culture and
      molecular biological techniques for bacterial identification, and to compare the
      microbial composition between crevices around anchor plates and gingival
      crevices. MATERIAL AND METHODS: Samples from crevices around titanium anchor
      plates and healthy gingival crevices of 17 subjects (aged 20-29) were cultured
      anaerobically, and isolated bacteria were identified by 16S rRNA sequencing.
      RESULTS: The average logarithm colony-forming units/ml were 6.84, 7.51 and 8.88
      in healthy anchor plate crevices, inflamed anchor plate crevices and healthy
      gingival crevices, respectively, indicating that the bacterial density of anchor
      plate crevices was lower than that of healthy gingival crevices. Of 184 strains
      isolated from healthy anchor plate crevices of seven subjects, 108 (59%) were
      anaerobic bacteria, while 73 (40%) were facultative bacteria. Predominant
      isolates were Gram-negative rods, such as Campylobacter (12%), Fusobacterium
      (10%) and Selenomonas (10%), and Gram-positive facultative bacteria, such as
      Actinomyces (17%) and Streptococcus (8.2%). Of 133 strains isolated from inflamed
      anchor plate crevices of three subjects, 110 (83%) were anaerobic bacteria, while
      predominant isolates were Gram-negative rods, such as Prevotella (47%),
      Fusobacterium (33%) and Campylobacter (16%). On the other hand, of 146 strains
      isolated from healthy gingival crevices of seven subjects, 98 (67%) were
      facultative bacteria, while 45 (31%) were anaerobic bacteria. Predominant
      isolates were Gram-positive facultative bacteria, such as Actinomyces (37%) and
      Streptococcus (20%). CONCLUSIONS: These results suggest that the environment in
      crevices around titanium orthodontic anchor plates is anaerobic and supportive of
      anaerobic growth of bacteria, which may trigger inflammation in the tissue around
      the plates.

PMID- 17224020
TI  - Characterization of the antioxidant profile of human saliva in peri-implant
      health and disease.
AB  - OBJECTIVES: Peri-implant disease is considered to be an inflammatory disease, but
      many aspects of its pathogenesis remain unknown. At present, peri-implant disease
      is considered to be initiated and perpetuated by a small group of predominantly
      Gram-negative, anaerobic, or micro-aerophilic bacteria that colonize the
      subgingival area. Bacteria cause the observed tissue destruction directly by
      toxic products and indirectly by activating host defence systems, i.e.
      inflammation. A variety of molecular species appears in the inflamed tissues,
      among them are reactive species such as free radicals and reactive oxygen species
      (ROS). The purpose of this study was to assess levels of various antioxidants in
      saliva to identify differences between the saliva of patients with healthy peri
      implant tissues and patients with peri-implant disease, and to examine whether
      the whole saliva of those with peri-implant disease conditions might have lower
      levels of antioxidants than that of healthy individuals. MATERIALS AND METHODS:
      Thirty healthy adult volunteers (14 men and 16 women) with implant-supported
      overdentures (Ankylos Biofunctional Implants) were selected from the group of
      patients from Tallinn Dental Clinic. Biochemical and clinical parameters
      evaluated were the following ones: the levels of urate, ascorbate,
      myeloperoxidase in saliva, total antioxidant status of saliva, pocket probing
      depth (mm), gingival index (0, 1, 2, or 3), and bleeding on probing (0 or 1).
      RESULTS AND CONCLUSION: Total antioxidant status (TAS) of saliva and
      concentration of uric acid and ascorbate, which are the main salivary
      antioxidants, are significantly decreased in patients with peri-implant disease.
      TAS in healthy subjects was 0.41+/-0.10 for resting saliva and 0.31+/-0.09 for
      stimulated saliva; in diseased subjects TAS was 0.19+/-0.07 and 0.12+/-0.03,
      respectively. In healthy subjects, the concentration of urate was 307.2+/-78.06
      microM/l in resting saliva and 241.5+/-89.09 microM/l in stimulated saliva. In
      diseased patients, the concentration of urate was 120+/-36.13 and 91.60+/-39.35
      microM/l, respectively. The concentration of ascorbate did not differ in resting
      and stimulated saliva. In healthy subjects, it was 2.79+/-0.81 mg/l and in
      diseased subjects, it was 1.54+/-0.30 mg/l. This may indicate that excessive ROS
      production in peri-implant disease is leading to the situation of excessive
      oxidative stress, which may be an important factor contributing the destruction
      of peri-implant tissues. The importance of these findings may be the better
      understanding of the processes involved in the pathogenesis of peri-implant
      disease and that the treatment of peri-implant disease may involve adjuvant anti
      oxidants supplementation together with cumulative interceptive supportive therapy
      concept introduced by Mombelli & Lang.

PMID- 17224021
TI  - Influence of cyclosporin A on quality of bone around integrated dental implants:
      a radiographic study in rabbits.
AB  - OBJECTIVES: To evaluate the influence of cyclosporin A (CsA) administration on
      bone around integrated dental implants assessed by a bone quality index and by
      quantitative subtraction radiography. MATERIAL AND METHODS: A total of 36 machine
      surface commercial implants were placed in 18 adult rabbits. After a 3-month
      healing period without any disturbance, the animals were randomly divided into
      three groups of six animals each. Group A was sacrificed at this time. CsA was
      injected subcutaneously in an immunosuppressive dose of 10 mg/kg/day in a test
      group (Group T), and a Group B served as a control, receiving only vehicle. After
      3 months of cyclosporin administration, the animals of both Groups B and T were
      sacrificed. Radiographs were obtained at implant surgery and at the day of
      sacrifice with a CMOS sensor. Bone quality around the implants was compared
      between the groups using a bone quality index and quantitative subtraction
      radiography. RESULTS: The bone analysis showed that in Group T, the bone quality
      changed dramatically from a dense cortical to a loose trabecular bone structure
      (P<0.0001, chi(2) test) while in Groups A and B there were no significant
      differences. Quantitative digital subtraction radiography showed significantly
      (P<0.05) lower gray shade values (radiographic density) in a region of bone
      formation around the implants in Group T (118+/-12) than in Groups A (161+/-6)
      and B (186+/-10). CONCLUSION: Within the limits of this study, CsA administration
      has a negative effect on the quality of bone around integrated dental implant.

PMID- 17224022
TI  - In vitro assessment of motility and proliferation of human osteogenic cells on
      different isolated extracellular matrix components compared with enamel matrix
      derivative by continuous single-cell observation.
AB  - OBJECTIVES: The composition of the extracellular matrix (ECM) plays a substantial
      role in bone remodelling, fracture healing and osseointegration of dental
      implants by regulating proliferation, migration and finally differentiation of
      osteogenic cell populations. Emdogain, a composition of an enamel matrix
      derivative (EMD), has been introduced as a potential candidate to promote tissue
      regeneration. We investigated whether EMD could serve as a potential promoter of
      cell proliferation and motility as a dynamic cell response and compared the
      results with the ubiquitous single ECM components type I collagen and laminin.
      MATERIAL AND METHODS: In the investigation presented, we used a continuous
      observation method for the analysis of migratory and proliferative patterns of
      individual cells. We analyzed the response of four osteoblastic cell lines to
      specific extracellular ligands (type I collagen, laminin and EMD) over a period
      of 24 h compared with untreated glass surface and bovine serum albumin (BSA) as
      control groups. RESULTS: Type I collagen and laminin promoted cell motility
      significantly compared with the control groups and, in part, compared with EMD as
      well. The analysis of all 451 investigated cells revealed the following mean
      values for cell motiliy: untreated glass (n=99): 5.46+/-2.74 microm/h, BSA
      (n=89): 6.35+/-2.43 microm/h, type I collagen (n=108): 8.77+/-3.42 microm/h,
      laminin (n=74): 9.89+/-5.10 microm/h and EMD (n=81): 7.92+/-3.35 microm/h.
      Proliferation rates on the different surfaces were heterogenous for all
      investigated cell lines and varied from 0% to 50% within 24 h without a
      correlation to cell motility. CONCLUSION: In our study, EMD promotes cell
      motility better than the control groups. The two investigated single ECM
      components type I collagen and laminin promoted cell motility superior to EMD.
      This supports the hypothesis that EMD promotes a less mobile but more
      differentiated osteogenic phenotype.

PMID- 17224023
TI  - Biocompatibility of different barrier membranes in cultures of human CRL 11372
      osteoblast-like cells: an immunohistochemical study.
AB  - OBJECTIVE: The aim of this study was to evaluate the biocompatibility of two
      different barrier materials in cultures of human osteoblast-like cells (CRL
      11372) in vitro. MATERIAL AND METHODS: Polylactic acid (Epi-Guide; EG) and
      collagen membrane (Bio-Collagen, BC) were examined. To analyze the effect of
      materials on cell proliferation, cell numbers and cell viability, cells were
      cultured on the barrier membranes for 24 and 72 h. Cells plated on culture dishes
      (CD) served as positive controls. Cell proliferation rate was assessed by the
      bromodeoxyuridine (BrdU) immunohistochemical technique. The cell numbers of each
      well were counted. Cell viability was estimated by counting the number of cells,
      which excluded trypan blue solution. Scanning electron microscopy (SEM) was used
      to observe the interactions between osteoblastic cells and barrier membranes.
      RESULTS: The highest number of BrdU-labeled cells were seen on CD after both of
      the time periods. In comparison with the other two groups, BC showed
      significantly fewer cells after both time periods. Regarding cell numbers, after
      24 and 72 h of incubations CD showed the highest number of cells. The number of
      viable cells was similar for all the groups. After 72 h for the EG group, SEM
      view showed flat cells. After 72-h time periods, the BC group revealed a weak
      adhesion of cells to the barriers. CONCLUSION: The results demonstrate that cells
      were able to proliferate on these materials and EG promoted the proliferation of
      human osteoblast like cells. We prefer to use the EG membrane.

PMID- 17224024
TI  - Behavior of CAL72 osteoblast-like cells cultured on zirconia ceramics with
      different surface topographies.
AB  - OBJECTIVES: Because of its inherent strength, biocompatibility, and tooth-like
      color, zirconia ceramics have the potential to become an alternative to titanium
      as dental implant material. This study aimed at investigating the osteoblastic
      response to yttrium-stabilized tetragonal zirconia polycrystal (Y-TZP) with
      different surface topographies. METHODS: CAL72 osteoblast-like cells were
      cultured on machined (TZP-m), airborne particle abraded (TZP-s), and airborne
      particle abraded and acid-etched Y-TZP (TZP-sa) surfaces. Polystyrene and
      airborne particle abraded with large grit and acid-etched (SLA) titanium served
      as a reference control. The surface topography was examined by scanning electron
      microscopy (SEM) and profilometry. At culture days 3, 6, and 12, cell
      proliferation, at day 12 cell morphology, and cell-covered surface area were
      determined. RESULTS: The surface roughness of Y-TZP was increased by airborne
      particle abrasion and additionally by acid etching. No statistically significant
      differences were found between average roughness (R(a)) and maximum peak-to
      valley height (R(p-v)) values of airborne particle abraded and acid-etched Y-TZP
      and SLA titanium. Whereas the cell proliferation assay revealed statistically
      significant greater values at day 3 for surface-treated Y-TZP and polystyrene
      cultures as compared with machined Y-TZP, no differences between the Y-TZP
      groups, SLA titanium, and polystyrene were observed at culture days 6 and 12.
      CONCLUSIONS: Cell morphology and cell-covered surface area were not affected by
      the type of substrate. The results suggest that roughened Y-TZP is an appropriate
      substrate for the proliferation and spreading of osteoblastic cells.

PMID- 17224025
TI  - Effects of ipriflavone on augmented bone using a guided bone regeneration
      procedure.
AB  - : This study investigated the effects of ipriflavone (IP) on augmented bone using
      a guided bone regeneration (GBR) procedure. In 15 rabbits, two titanium caps were
      placed into calvarial bone for GBR. The animals were divided into three groups:
      the No-IP (no intake of IP), Post-IP (IP orally, 10 mg/kg/day after GBR), and Pre
      IP (IP intake beginning before GBR) groups. One cap was removed from each rabbit
      after 3 months, and the remaining site was a control. One month after one cap
      removal, all the animals were euthanized, and histologic and histomorphometric
      analyses were performed. In all of the groups, the newly generated tissue was of
      varying size, and it consisted of thin pieces of mineralized bone and large
      marrow spaces with fat cells and some hematopoietic cells. In all of the control
      sites, the newly generated tissue was noted and almost filled the space under the
      cap. There was a significant difference between groups No-IP and Pre-IP (93.8+/
      4.6% vs. 98.5+/-0.8%, P<0.05). The tissue generated at the test sites in all of
      the groups was resorbed, and its original shape and volume were not maintained 1
      month after one cap removal. In particular, the greatest percentage,
      approximately 20% of the newly generated tissue, was resorbed in the No-IP group
      (93.8+/-4.6% vs. 73.9+/-3.7%, P<0.05), and approximately 11% and 15% in groups
      Post-IP and Pre-IP, respectively. The relative amount of mineralized bone
      generated at the control and test sites was significantly larger in groups Post
      IP and Pre-IP when compared with group No-IP, except for the test site between
      groups No-IP and Post-IP (P<0.05). Therefore, the amount of mineralized tissue
      generated appeared to increase with an increase in the total IP dose. Within the
      limitations of this rabbit experimental model, we conclude that the daily intake
      of IP before or after GBR inhibits the resorption of augmented tissue and would
      be useful for improving the quality of newly generated bone beyond the skeletal
      envelope.

PMID- 17224026
TI  - Bone formation after sinus augmentation with engineered bone.
AB  - OBJECTIVES: The aim of the following investigation was to quantify the resorption
      rate of tissue-engineered bone grafts in the maxillary sinus using volume
      measurements. MATERIAL AND METHODS: Sinus floor augmentation using autologous
      bone grafts from the iliac crest (n=17, group 1) was compared with commercially
      produced transplants of human cells seeded on polyglycolid-polylactid (PLGA)
      scaffolds (Oral Bone) (n=14, group 2). RESULTS: The total resorption rate for
      autologous transplants 3 months post operation was 29%, while the tissue
      engineered bone showed a resorption rate of 90%. The autologous bone had a bone
      density of up to 266-551 Hounsfield units (HU), while sufficient mineralization
      of tissue-engineered bone was found in only one case (152 HU). CONCLUSION: In
      this clinical study, the use of autologous cancellous bone grafts in sinus
      augmentation was more reliable than scaffolds containing cultured osteoblasts.
      Further tissue-engineered bone transplants should be examined to draw general
      conclusions about the use of tissue-engineered grafts compared with autologous
      bone grafts for maxillary sinus augmentation.

PMID- 17224027
TI  - Le Fort I osteotomy with interpositional bone grafts and delayed oral implants
      for the rehabilitation of extremely atrophied maxillae: a 1-9-year clinical
      follow-up study on humans.
AB  - AIM: The purpose of this clinical follow-up study was to report the clinical
      outcome of osseointegrated implants placed in extremely atrophied edentulous
      maxillae after Le Fort I osteotomy and interpositional autogenous iliac bone
      grafts. PATIENTS AND METHODS: In a 10-year period (1995-2004), 39 patients, 18
      males and 21 females, aged from 32 to 76 years, presenting with severely
      atrophied edentulous maxillae were treated with Le Fort I osteotomy and
      interpositional iliac bone grafts. Four to 8 months after the reconstructive
      procedure, 281 osseointegrated implants were placed in the reconstructed
      maxillae. Four to 8 months afterwards, abutments were connected and the
      prosthetic rehabilitation started. The mean follow-up period of implants after
      the start of prosthetic loading was 45.9 months (range: 12-108 months). RESULTS:
      The reconstructive procedure was successful in 38 of 39 patients. In one patient,
      partial loss of the inlay graft occurred before implant placement. Six patients
      (42 implants) dropped out of the study. Fifteen implants were removed during the
      follow-up period, due to loss of integration. Thirty-two implants, although
      integrated, presented with peri-implant bone-level changes higher than those
      proposed for successful implants. Cumulative survival and success rates of
      implants were 94.5% and 82.9%, respectively. CONCLUSION: Results from this study
      showed that Le Fort I osteotomy with interpositional bone grafts followed by
      delayed implant placement is an acceptable means to rehabilitate edentulous
      patients affected by extremely atrophied edentulous maxillae. Survival rates of
      implants are consistent with those related to implants placed in native, non
      reconstructed bone. Conversely, the success rate of implants resulted to be lower
      as compared with those obtained for implants placed in native bone.

PMID- 17224028
TI  - Vertical ridge augmentation with guided bone regeneration in association with
      dental implants: an experimental study in dogs.
AB  - AIM: To evaluate the effect of using guided bone regeneration (GBR) with a
      titanium-reinforced e-PTFE membrane in alveolar bone defects with titanium
      implants. MATERIAL AND METHODS: Following extraction of three mandibular
      premolars and a molar on both sides of the jaw in three dogs, alveolar bone
      defects (depth: 5-7 mm) were produced. After 4 months, three implants were
      inserted into each defect to a depth of approximately 4 mm, so that their coronal
      portion was protruding about 5 mm. Four sides in the dogs were assigned to a test
      group and the remaining two sides to a control group. The 12 implants in the test
      group were covered with a reinforced e-PTFE membrane. The space under the
      membrane was filled with peripheral venous blood from the animal, and the flaps
      were sutured over the membrane. The six control implants received no membrane
      before the suturing of the flaps to complete wound closure. The animals were
      sacrificed after 6 months, and non-decalcified histological specimens of the
      implants and surrounding tissues were prepared. RESULTS: Histologic and
      histomorphometric analyses revealed a significantly (Mann-Whitney test; P=0.08)
      larger amount of bone fill in the test group (mean=57.42%) than in the controls
      (mean=11.65%), and clinical evaluation of one test site showed that the implants
      were completely covered with tissue resembling bone. In most of the specimens,
      bone had grown in height close to, or in direct contact with the membrane.
      However, the new bone generally was not in direct contact with the implants.
      Regularly, a zone of dense connective tissue was interposed between the implants
      and the newly formed bone. CONCLUSION: The formation of even considerable amounts
      of bone following vertical ridge augmentation with GBR and implants was not
      accompanied by predictable osseointegration of the implants.

PMID- 17224029
TI  - Fully vs. partially rough implants in maxillary sinus floor augmentation: a
      randomized-controlled clinical trial.
AB  - OBJECTIVES: To compare implants with a rough surface in their whole length (FR)
      with implants having a 2 mm coronal machined portion (PR) when used in
      association with a sinus-lift procedure. MATERIAL AND METHODS: Twenty-six
      patients with 2 mm< or =x< or =9 mm residual alveolar crest were prosthetically
      restored with implants after a staged sinus-lift procedure using osteotomes. In
      13 randomly chosen patients, no more than one FR implant was placed (test group),
      while the rest were PR implants. The other 13 patients received only PR implants
      (control group). For comparisons, only one implant from each patient was used,
      i.e., from the test group only the 13 FR implants were used, while from the
      control group, one PR implant was randomly chosen. The presence/absence of
      plaque, BOP, PPD and REC were registered at the day of delivery of the
      restorations and after 1 year. Residual alveolar crest height and marginal bone
      levels around the implants were evaluated on standardized periapical radiographs
      taken at various stages. RESULTS: Four FR and two PR implants were lost, and the
      cumulative survival rate was 82.9% (six lost out of 35). There were no
      significant differences between the two groups. Implant type, residual alveolar
      crest height, time of osseointegration, time of implant loading and smoking did
      not seem to influence implant survival. CONCLUSIONS: FR and PR implants placed in
      augmented sinuses did not differ in their clinical performance.

PMID- 17224030
TI  - Adapted preparation technique for screw-type implants: explorative in vitro pilot
      study in a porcine bone model.
AB  - OBJECTIVE: The aim of this study was to quantify the effect of adapted
      preparation on the insertion torque of self-tapping implants in cancellous bone.
      In adapted preparation, bone condensation - and thus, insertion torque - is
      controlled by changing the diameter of the drilling. MATERIAL AND METHODS: After
      preparation of cancellous porcine vertebral bone with drills of 2.85, 3, 3.15 or
      3.35 mm final diameters, Branemark sytem Mk III implants (3.75 x 11.5 mm) were
      inserted in 141 sites. During implantation, the insertion torque was recorded.
      Prior to implant insertion, bone mineralization (bone mineral density (BMD)) was
      measured with dental quantative computed tomography. The BMD values measured at
      the implant position were correlated with insertion torque for varying bone
      condensation. RESULTS: Based on the average torque recorded during implant
      insertion into the pre-drilled canals with a diameter of 3 mm, torque increased
      by approximately 17% on reducing the diameter of the drill by 5% (to 2.85 mm). On
      increasing the diameter of the osteotomy to 3.15 mm (5%) or 3.35 mm (12%), torque
      values decreased by approximately 21% and 50%, respectively. CONCLUSION: The
      results demonstrate a correlation between primary stability (average insertion
      torque) and the diameter of the implant bed on using a screw-shaped implant.
      Thus, using an individualized bone mineralization-dependent drilling technique,
      optimized torque values could be achieved in all tested bone qualities with BMDs
      ranging from 330 to 500 mg/cm(3). The results indicate that using a bone
      dependent drilling technique, higher torque values can also be achieved in poor
      bone using an individualized drilling resulting in higher bone condensation. As
      immediate function is dependent on primary stability (high insertion torque),
      this indicates that primary stability can be increased using a modified drilling
      technique in lesser mineralized bone.

PMID- 17224031
TI  - Cementable implant crowns composed of cast superstructure frameworks luted to
      electroformed primary copings: an in vitro retention study.
AB  - OBJECTIVE: The aim of this in vitro study was to investigate, on ITI solid
      abutments, the retention values of single crowns fabricated using an alternative
      prosthetic solution: secondary cast superstructure luted to an electroformed
      primary coping. MATERIALS AND METHODS: Fifty standard 4.1 mm ITI implants and 5.5
      mm high ITI machined abutments were assembled and mounted in acrylic resin.
      Implant/abutment assemblies were randomly divided into two groups. In the test
      group, primary galvanic caps were directly fabricated on implant abutments
      (A.G.C. Micro machine), and a secondary cast noble alloy superstructure was luted
      on each primary galvanic cap with a resin cement (Nimetic Cem). In the control
      group, prefabricated burn-out caps were used for casting the metal frameworks.
      Test and control crowns were cemented using a resin cement (Panavia 21). After
      storage at 37 degrees for 24 h, the specimens were subjected to a pull-out test
      using an Instron universal testing machine. The load required to dislodge each
      sample and the respective mode of failure were recorded. Means and standard
      deviations of loads at failure were analyzed using ANOVA. Statistical
      significance was set at P< or =0.05. RESULTS: The retention values (+/-SD) of
      loads at failure were 67.26 (+/-16.61) for the test group and 44.03 (+/-9.45) for
      the control group. In the test group no separation occurred between the
      electroformed (galvanic) primary cap and the secondary superstructure.
      CONCLUSIONS: The results showed that this prosthetic solution is superior on
      retentive performance than the conventional cast framework. An added clinical
      advantage of this novel method is its potential to provide a totally passive fit.
      Further in vitro and in vivo studies involving multiple-unit restorations are
      needed in order to more generally validate this prosthetic concept.

PMID- 17224032
TI  - Inflammation associated with implants with different surface types.
AB  - OBJECTIVES: The aim of this study was to determine the nature of the inflammatory
      infiltrate associated with different transmucosal implant surfaces in dogs.
      METHODS: Three experimental and one control single-stage implants were randomly
      placed on each side of the jaw in eight dogs. The transmucosal portion of the
      test implants consisted of an acid-etched surface (type A), a machined surface
      with a circumferential groove (type C) and a surface prepared by mild anodic
      oxidation (type D). The control was a standard machined surface (type B). In
      order to determine the response to the different surfaces, plaque control was
      carried out twice weekly following placement of the implants for the entire
      period of the experiment. At 6 months, gingival biopsies and plaque samples were
      obtained. The area of inflammatory infiltrate and the nature of the infiltrating
      cell types were determined using immunohistology. Real-time polymerase chain
      reaction was used to identify putative periodontal pathogens. RESULTS:
      Inflammatory infiltrates were associated with all implant surfaces and were
      commonly found subepithelially and perivascularly. T cells were the predominant
      infiltrating cell type in all lesions, associated with the different surfaces. In
      all lesions the CD4 : CD8 ratio was approximately 2 : 1. Statistical analysis
      showed that the type C surface (machined surface with a groove) had significantly
      larger inflammatory infiltrates than the type B surface (machined surface without
      a groove; P<0.05). No statistically significant differences were found with
      respect to the size of the inflammatory infiltrates or in terms of the nature of
      infiltrating cells. However, despite the intensive plaque control regime, plaque
      was present on all implant surfaces at the time of biopsy 6 months after
      placement. All implants had similar numbers of Tannerella forsythia,
      Fusobacterium nucleatum and Porphyromonas gingivalis. Actinobacillus
      actinomycetemcomitans, was not detected in any sample. CONCLUSIONS: These results
      suggest that the development of inflammation associated with implants is
      independent of surface type, but is nevertheless associated with the presence of
      plaque. The different surfaces had no influence on the nature of the infiltrate,
      with T cells being the predominant cell type in all lesions. Finally, the
      different implant surface types seemed not to influence the peri-implant
      microbiota. However, the presence of the circumferential groove tended to be
      associated with larger infiltrates. Whether this is due to increased plaque
      accumulation remains to be determined.

PMID- 17224033
TI  - Decontamination of rough titanium surfaces with diode lasers: microbiological
      findings on in vivo grown biofilms.
AB  - OBJECTIVES: The bactericidal efficacy of diode lasers has already been
      demonstrated in vitro. We investigated the reduction of aerobe bacteria -
      colonizing rough titanium samples in biofilms intraorally grown - by diode lasers
      of different wave lengths. MATERIAL AND METHODS: Twenty-two volunteers
      participated in the trial. They were fitted for 10 days with custom-made
      intraoral plastic splints carrying titanium sleeves. A part of the sleeves was
      then irradiated with diode lasers in different modes. The other part remained non
      irradiated and served as control. Directly after irradiation, the sleeves were
      swabbed and the gained bacteria were first examined microscopically and then were
      cultured under aerobic conditions. RESULTS: The bacteria in the controls and in
      the treated samples were quantified. A comparison with the controls revealed a
      marked overall reduction of bacterial colonization in all irradiated sleeves.
      Continuous irradiation for 20 s reduced bacteria counts by 99.67% at 810 nm and
      99.58% at 980 nm. Repeating the 20 s exposure five times reduced counts by 99.98%
      at 810 nm and by 99.39% at 980 nm. A 98.86% reduction was seen after irradiation
      in pulsed mode. A further analysis in respect of different isolated bacteria
      revealed that the streptococci group was reduced by 99.29-99.99%, while the
      staphylococci group was reduced to a lesser extent in the range 94.67-99.99%.
      CONCLUSION: The results are of clinical relevance. In comparison with the mean
      bacterial counts of the untreated samples, all irradiation programs studied in
      this investigation reduced mean bacterial colonization in a biofilm on intraoral
      rough titanium surfaces by more than 98%. The actual extent of reduction was
      dependent on the bacteria species as well as on the irradiation mode.

PMID- 17224034
TI  - Influence of the application of platelet-enriched plasma in oral mucosal wound
      healing.
AB  - PURPOSE: The aim of this study was to describe and quantify the therapeutic value
      of platelet concentrate on the capillary density in oral mucosal wound healing.
      MATERIAL AND METHODS: The subjects included 10 healthy edentulous patients who
      underwent bilaterally a sinus floor elevation procedure and a buccal onlay graft
      with autologous iliac crest bone for maxillary reconstruction. During surgery,
      platelet-rich plasma (PRP) was prepared from a blood sample taken from the
      patient. After randomization in a split-mouth design, at one side PRP was
      administered in the wound and at the contralateral side a placebo. At baseline,
      microvascular capillary density was scored with the orthogonal polarization
      spectral (OPS) imaging technique and repeated measurements were performed
      postoperatively on a daily basis until the tenth day, after which measurements
      were continued weekly until the fifth postoperative week. RESULTS: Ten patients,
      five males and five females, were included in the study with a mean age of 54.2+/
      9.1 years for females and 57.6+/-6.9 years for males. Donor platelet counts from
      whole blood had a mean value of 248.5+/-13.5 x 10(9)/l, while the value of
      platelet counts in the PRP had a mean of 975.9+/-97.9 x 10(9)/l. Wound healing
      was significantly accelerated in the PRP-treated mucosal wounds during the first
      10 postoperative days. After the second week, no obvious differences between the
      PRP or placebo side could be noted. CONCLUSION: PRP has a strong stimulant effect
      on capillary regeneration in wound healing. These effects are mainly noticeable
      during the early stages of wound healing.

PMID- 17224035
TI  - Implants in children with ectodermal dysplasia: a case report and literature
      review.
AB  - The replacement of teeth by implants is usually restricted to patients with
      completed craniofacial growth. Implant insertions in children or adolescents are
      circumvented due to several unfavorable potential effects including trauma to
      tooth germs, tooth eruption disorders and multidimensional restrictions of
      skeletal craniofacial growth. Moreover, the functional and esthetic results of
      the oral rehabilitation are only temporary acceptable. However, to a small number
      of pediatric patients suffering congenitally from severe hypodontia caused by
      syndromes such as ectodermal dysplasia, conventional prosthodontic
      rehabilitations are insufficient. We report the case of a boy with ectodermal
      dysplasia who exhibited a severe hypodontia and who was treated with implants
      inserted into the anterior mandible at the age of 8 years. The implants were
      functionally loaded and resulted in a high patient satisfaction. We recommend the
      early insertion of dental implants in children with severe hypodontia. Reviewing
      the current literature, several aspects of syndromic hypodontia, patient
      selection and implant planning are discussed.

PMID- 17224036
TI  - Referrals to intensive care: a region-wide audit.

PMID- 17224038
TI  - A rare disease.
AB  - Thrombocytopenia is a common finding in critically ill patients. Heparin-induced
      thrombocytopenia is an infrequent cause of a low platelet count. Intensivists
      should use the diagnostic classification system developed by the International
      Society on Thrombosis and Haemostasis to diagnose heparin-induced
      thrombocytopenia. The clinical relevance of the presence of anti-heparin/platelet
      factor 4 complex autoantibodies in the absence of clinical heparin-induced
      thrombocytopenia remains unknown.

PMID- 17224039
TI  - Recombinant activated protein C in sepsis: endothelium protection or endothelium
      therapy?
AB  - Endothelium dysfunction is one of the hallmarks of sepsis. Looney and Mattay, in
      the previous issue of Critical Care, highlight the role of activated protein C
      (APC) as a protective endothelial drug in septic situations. Nevertheless, the
      results of in vivo studies are less explicit and it remains uncertain whether
      these properties are relevant in human septic shock. Before considering
      recombinant APC (rAPC) as a therapeutic drug for the endothelium, we have to
      demonstrate its efficiency to protect or to reduce endothelium injury when
      infused a long time after the septic challenge. Nevertheless, if rAPC is
      efficient when infused in the early phase of septic challenge, we thus need to
      treat our patients earlier. At the least, genetically engineered variants have
      been designed with greater anti-apoptotic activity and reduced anticoagulant
      activity relative to wild-type APC. Further studies are needed to demonstrate the
      usefulness of these variants in septic shock therapy.

PMID- 17224040
TI  - Anticipating the 1,000 dollar genome.
AB  - A new generation of DNA-sequencing platforms will become commercially available
      over the next few years. These instruments will enable re-sequencing of human
      genomes at a previously unimagined throughput and low cost. Here, I examine why
      the 1,000 dollar human genome is an important goal for research and clinical
      diagnostics, and what will be required to achieve it.

PMID- 17224037
TI  - Lipid peroxidation, oxidative stress genes and dietary factors in breast cancer
      protection: a hypothesis.
AB  - We have recently proposed that lipid peroxidation may be a common mechanistic
      pathway by which obesity and hypertension lead to increased renal cell cancer
      risk. During this exercise, we noted a risk factor swap between breast and kidney
      cancer (oophorectomy and increased parity, detrimental for kidney, beneficial for
      breast; high blood pressure, detrimental for kidney, beneficial for breast when
      it occurs during pregnancy; alcohol, beneficial for kidney, detrimental for
      breast, and so on). We have subsequently proposed the hypothesis that lipid
      peroxidation represents a protective mechanism in breast cancer, and reviewed the
      evidence of the role of lipid peroxidation on established hormonal and non
      hormonal factors for breast cancer. Here, we review the evidence in support of
      lipid peroxidation playing a role in the relationships between dietary factors
      and breast cancer. Available evidence implicates increased lipid peroxidation
      products in the anti-carcinogenic effect of suspected protective factors for
      breast cancer, including soy, marine n-3 fatty acids, green tea, isothiocyanates,
      and vitamin D and calcium. We also review the epidemiological evidence supporting
      a modifying effect of oxidative stress genes in dietary factor-breast cancer
      relationships.

PMID- 17224042
TI  - Imaging with isotopes: high resolution and quantitation.

PMID- 17224043
TI  - Efficient classification of complete parameter regions based on semidefinite
      programming.
AB  - BACKGROUND: Current approaches to parameter estimation are often inappropriate or
      inconvenient for the modelling of complex biological systems. For systems
      described by nonlinear equations, the conventional approach is to first
      numerically integrate the model, and then, in a second a posteriori step, check
      for consistency with experimental constraints. Hence, only single parameter sets
      can be considered at a time. Consequently, it is impossible to conclude that the
      "best" solution was identified or that no good solution exists, because parameter
      spaces typically cannot be explored in a reasonable amount of time. RESULTS: We
      introduce a novel approach based on semidefinite programming to directly identify
      consistent steady state concentrations for systems consisting of mass action
      kinetics, i.e., polynomial equations and inequality constraints. The duality
      properties of semidefinite programming allow to rigorously certify infeasibility
      for whole regions of parameter space, thus enabling the simultaneous multi
      dimensional analysis of entire parameter sets. CONCLUSION: Our algorithm reduces
      the computational effort of parameter estimation by several orders of magnitude,
      as illustrated through conceptual sample problems. Of particular relevance for
      systems biology, the approach can discriminate between structurally different
      candidate models by proving inconsistency with the available data.

PMID- 17224041
TI  - The Heterochromatin Protein 1 family.
AB  - Heterochromatin Protein 1 (HP1) was first discovered in Drosophila as a dominant
      suppressor of position-effect variegation and a major component of
      heterochromatin. The HP1 family is evolutionarily conserved, with members in
      fungi, plants and animals but not prokaryotes, and there are multiple members
      within the same species. The amino-terminal chromodomain binds methylated lysine
      9 of histone H3, causing transcriptional repression. The highly conserved carboxy
      terminal chromoshadow domain enables dimerization and also serves as a docking
      site for proteins involved in a wide variety of nuclear functions, from
      transcription to nuclear architecture. In addition to heterochromatin packaging,
      it is becoming increasingly clear that HP1 proteins have diverse roles in the
      nucleus, including the regulation of euchromatic genes. HP1 proteins are amenable
      to posttranslational modifications that probably regulate these distinct
      functions, thereby creating a subcode within the context of the 'histone code' of
      histone posttranslational modifications.

PMID- 17224044
TI  - Worked examples of alternative methods for the synthesis of qualitative and
      quantitative research in systematic reviews.
AB  - BACKGROUND: The inclusion of qualitative studies in systematic reviews poses
      methodological challenges. This paper presents worked examples of two methods of
      data synthesis (textual narrative and thematic), used in relation to one review,
      with the aim of enabling researchers to consider the strength of different
      approaches. METHODS: A systematic review of lay perspectives of infant size and
      growth was conducted, locating 19 studies (including both qualitative and
      quantitative). The data extracted from these were synthesised using both a
      textual narrative and a thematic synthesis. RESULTS: The processes of both
      methods are presented, showing a stepwise progression to the final synthesis.
      Both methods led us to similar conclusions about lay views toward infant size and
      growth. Differences between methods lie in the way they dealt with study quality
      and heterogeneity. CONCLUSION: On the basis of the work reported here, we
      consider textual narrative and thematic synthesis have strengths and weaknesses
      in relation to different research questions. Thematic synthesis holds most
      potential for hypothesis generation, but may obscure heterogeneity and quality
      appraisal. Textual narrative synthesis is better able to describe the scope of
      existing research and account for the strength of evidence, but is less good at
      identifying commonality.

PMID- 17224045
TI  - Case report: quantification of methadone-induced respiratory depression using
      toxicokinetic/toxicodynamic relationships.
AB  - INTRODUCTION: Methadone, the most widely delivered maintenance therapy for heroin
      addicts, may be responsible for life-threatening poisonings with respiratory
      depression. The toxicokinetics and the toxicokinetic/toxicodynamic (TK/TD)
      relationships of methadone enantiomers have been poorly investigated in acute
      poisonings. The aim of this study was to describe the relationships between
      methadone-related respiratory effects and their corresponding concentrations.
      METHODS: We report a 44-year-old methadone-maintained patient who ingested a 240
      mg dose of methadone. He was found comatose with pinpoint pupils and respiratory
      depression. He was successfully treated with intravenous naloxone infusion over
      the course of 31 hours at a rate adapted to maintain normal consciousness and
      respiratory rate. We performed a TK/TD analysis of the naloxone infusion rate
      needed to maintain his respiratory rate at more than 12 breaths per minute (as
      toxicodynamics parameter) versus plasma R,S- and R-methadone concentrations (as
      toxicokinetics parameter), determined using an enantioselective high-performance
      liquid chromatography assay. RESULTS: Initial plasma R,S-methadone concentration
      was 1,204 ng/ml. Decrease in plasma R- and S-methadone concentrations was linear
      and demonstrated a first-order pharmacokinetics (maximal observed concentrations
      566 and 637 ng/ml, half-lives 16.1 and 13.2 hours, respectively). TK/TD
      correlation between naloxone infusion rate and R,S- and R-methadone
      concentrations fitted well a sigmoidal Emax model (concentration associated with
      a half-maximum effect [EC50] 334 and 173 ng/ml, Hill coefficient 10.0 and 7.8,
      respectively). In our chronically treated patient, EC50 values were in the range
      of previously reported values regarding methadone analgesic effects, suggesting
      that plasma methadone concentrations to prevent withdrawal are lower than those
      associated with methadone analgesic effects. CONCLUSION: After the ingestion of a
      toxic dose of a racemic mixture, plasma R- and S-enantiomer concentrations
      decreased in parallel. Despite large inter-individual variability in methadone
      toxicokinetics and toxicodynamics, TK/TD relationships would be helpful for
      providing quantitative data regarding the respiratory response to methadone in
      poisonings. However, further confirmatory TK/TD data are needed.

PMID- 17224047
TI  - Urine carcinoembryonic antigen levels are more useful than serum levels for early
      detection of Bilharzial and non-Bilharzial urinary bladder carcinoma:
      observations of 43 Egyptian cases.
AB  - BACKGROUND: Both urinary bilharziasis and urothelial neoplasia are associated
      with increased production of tissue carcinoembryonic antigen (CEA). PATIENTS AND
      METHODS: Urine and serum CEA were determined in 43 patients with urinary bladder
      carcinoma including 22 post bilharzial and 21 nonbiharzial cases, in addition to
      10 normal control cases. RESULTS: A significant increase was detected in both
      urine and serum CEA levels with bladder carcinoma compared to control cases.
      Urinary CEA was significantly elevated in 86% of bilharzial, versus 62% in
      nonbilharzial bladder carcinoma. Only 10.5% of control cases had urinary CEA
      elevation. The mean urinary CEA in bilharzial, was higher than that of
      nonbilharzial carcinoma, but the difference was not statistically significant.
      There was a definite relationship between urine CEA and the stage of malignancy;
      the higher the stage, the higher the level of urine CEA. No relationship could be
      detected between the stage of malignancy and serum CEA, or between the grades of
      malignancy and urine or serum CEA levels. CONCLUSION: Urinary CEA is more useful
      than serum CEA in the early detection of urotherlial carcinoma particularly if
      provoked by bilharziasis. Its level is also correlated with the tumor stage.

PMID- 17224048
TI  - Addressing the human resources crisis: a case study of the Namibian health
      service.
AB  - BACKGROUND: This paper addresses an important practical challenge to staff
      management. In 2000 the United Nations committed themselves to the ambitious
      targets embodied in the Millennium Development Goals (MDGs). Only five years
      later, it was clear that poor countries were not on track to achieve them. It was
      also clear that achieving the three out of the eight MDGs that concern health
      would only be possible if the appropriate human resources (HR) were in place.
      METHODS: We use a case study based on semi-structured interview data to explore
      the steps that Namibia, a country facing severe health problems that include an
      alarmingly high AIDS infection rate, has taken to manage its health workers.
      RESULTS: In the fifteen years since independence, Namibia has patiently built up
      a relatively good strategic framework for health policy in the context of
      government policy as a whole, including strong training arrangements at every
      level of health staffing, and it has brought HIV/AIDS under the strategic
      umbrella through its National Strategic Plan for HIV/AIDS. Its major weakness is
      that it has not kept pace with the rise in HIV/AIDS and TB infection: the
      community counselling service, still at the pilot stage at the time of this
      study, was the only specific response. That has created a tension between
      building long-term capacity in a strategic context and responding to the short
      term demands of the AIDS and TB crisis, which in turn affects the ability of HR
      to contribute to improving health outcomes. CONCLUSION: It is suggested that
      countries like Namibia need a new paradigm for staffing their health services.
      Building on the existing strategic framework, it should target the training of
      'mid-level cadres'. Higher-level cadres should take on the role of supporting and
      monitoring the mid-level cadres. To do that, they will need management training
      and a performance management framework for staff support and monitoring.

PMID- 17224049
TI  - Molecular surveillance of drug-resistance associated mutations of Plasmodium
      falciparum in south-west Tanzania.
AB  - BACKGROUND: In Tanzania, drug-resistant malaria parasites are an increasing
      public health concern. Because of widespread chloroquine (CQ) resistance Tanzania
      changed its first line treatment recommendations for uncomplicated malaria from
      CQ to sulfadoxine-pyrimethamine (SP) in 2001. Loss of SP sensitivity is
      progressing rapidly. SP resistance is associated with mutations in the
      dihydrofolate reductase (pfdhfr) and dihydropteroate synthase (pfdhps) genes.
      METHODS: In samples from 86 patients with uncomplicated Plasmodium falciparum
      malaria from Mbeya and Matema, Mbeya region, south-western Tanzania, the
      occurrence of mutations was investigated in the pfcrt and pfmdr1 genes which are
      associated with CQ resistance and in pfdhfr and pfdhps, conferring SP resistance,
      as well in cytb which is linked to resistance to atovaquone. RESULTS: Pfcrt T76
      occurs in 50% and pfmdr1 Y86 in 51.7%. Pfdhfr triple mutations coexisting with
      pfdhps double mutations were detected in 64.3% of the P. falciparum isolates.
      This quintuple mutation is seen as a possible predictive molecular marker for SP
      treatment failure. Mutations of the cytb gene were not detected. CONCLUSION:
      These findings of a high prevalence of mutations conferring SP resistance
      correspond to data of in vivo SP efficacy studies in other regions of Tanzania
      and underline the recommendation of changing first-line treatment to artemisinin
      based combination therapy.

PMID- 17224050
TI  - Interaction between Bluetongue virus outer capsid protein VP2 and vimentin is
      necessary for virus egress.
AB  - BACKGROUND: The VP2 outer capsid protein Bluetongue Virus (BTV) is responsible
      for receptor binding, haemagglutination and eliciting host-specific immunity.
      However, the assembly of this outer capsid protein on the transcriptionally
      active viral core would block transcription of the virus. Thus assembly of the
      outer capsid on the core particle must be a tightly controlled process during
      virus maturation. Earlier studies have detected mature virus particles associated
      with intermediate filaments in virus infected cells but the viral determinant for
      this association and the effect of disrupting intermediate filaments on virus
      assembly and release are unknown. RESULTS: In this study it is demonstrated that
      BTV VP2 associates with vimentin in both virus infected cells and in the absence
      of other viral proteins. Further, the determinants of vimentin localisation are
      mapped to the N-terminus of the protein and deletions of amino acids between
      residues 65 and 114 are shown to disrupt VP2-vimentin association. Site directed
      mutation also reveals that amino acid residues Gly 70 and Val 72 are important in
      the VP2-vimentin association. Mutation of these amino acids resulted in a soluble
      VP2 capable of forming trimeric structures similar to unmodified protein that no
      longer associated with vimentin. Furthermore, pharmacological disruption of
      intermediate filaments, either directly or indirectly through the disruption of
      the microtubule network, inhibited virus release from BTV infected cells.
      CONCLUSION: The principal findings of the research are that the association of
      mature BTV particles with intermediate filaments are driven by the interaction of
      VP2 with vimentin and that this interaction contributes to virus egress.
      Furthermore, i) the N-terminal 118 amino acids of VP2 are sufficient to confer
      vimentin interaction. ii) Deletion of amino acids 65-114 or mutation of amino
      acids 70-72 to DVD abrogates vimentin association. iii) Finally, disruption of
      vimentin structures results in an increase in cell associated BTV and a reduction
      in the amount of released virus from infected cells.

PMID- 17224051
TI  - Microglia activation in sepsis: a case-control study.
AB  - BACKGROUND: Infection induces an acute phase response that is accompanied by non
      specific symptoms collectively named sickness behavior. Recent observations
      suggest that microglial cells play a role in mediating behavioral changes in
      systemic infections. In animal models for sepsis it has been shown that after
      inducing lipopolysaccharide, LPS, microglia in the brain were activated. The aim
      of this study was to investigate whether activation of microglia can be detected
      in patients who died of sepsis. METHODS: In a case-control study brain tissue of
      13 patients who died with sepsis was compared with that of 17 controls. Activated
      microglia were identified by expression of MHC-class II antigens and CD68.
      Microglia activation was analyzed by a semiquantitative score combining both the
      number of the immunoreactive cells and their morphology. RESULTS: In patients who
      died with sepsis there was a significant increase in activated microglia in the
      grey matter when stained with CD68 compared to controls. This effect was
      independent of the effect of age. CONCLUSION: This study shows for the first time
      in human brain tissue an association between a systemic infection and activation
      of microglia in the brain. Activated microglia during sepsis could play a role in
      behavioral changes associated with systemic infection.

PMID- 17224053
TI  - Proteomics profiling of urine with surface enhanced laser desorption/ionization
      time of flight mass spectrometry.
AB  - BACKGROUND: Urine consists of a complex mixture of peptides and proteins and
      therefore is an interesting source of biomarkers. Because of its high throughput
      capacity SELDI-TOF-MS is a proteomics technology frequently used in biomarker
      studies. We compared the performance of seven SELDI protein chip types for
      profiling of urine using standard chip protocols. RESULTS: Performance was
      assessed by determining the number of detectable peaks and spot to spot variation
      for the seven array types and two different matrices: SPA and CHCA. A urine
      sample taken from one healthy volunteer was applied in eight-fold for each chip
      type/matrix combination. Data were analyzed for total number of detected peaks
      (S/N > 5). Spot to spot variation was determined by calculating the average CV of
      peak intensities. In addition, an inventory was made of detectable peaks with
      each chip and matrix type. Also the redundancy in peaks detected with the
      different chip/matrix combinations was determined. A total of 425 peaks (136 non
      redundant peaks) could be detected when combining the data from the seven chip
      types and the two matrices. Most peaks were detected with the CM10 chip with CHCA
      (57 peaks). The Q10 with CHCA (51 peaks), SEND (48 peaks) and CM10 with SPA (48
      peaks) also performed well. The CM10 chip with CHCA also has the best
      reproducibility with an average CV for peak intensity of 13%. CONCLUSION: The
      combination of SEND, CM10 with CHCA, CM10 with SPA, IMAC-Cu with SPA and H50 with
      CHCA provides the optimal information from the urine sample with good
      reproducibility. With this combination a total of 217 peaks (71 non-redundant
      peaks) can be detected with CV's ranging from 13 to 26%, depending on the chip
      and matrix type. Overall, CM10 with CHCA is the best performing chip type.

PMID- 17224052
TI  - Production of recombinant antibody fragments in Bacillus megaterium.
AB  - BACKGROUND: Recombinant antibodies are essential reagents for research,
      diagnostics and therapy. The well established production host Escherichia coli
      relies on the secretion into the periplasmic space for antibody synthesis. Due to
      the outer membrane of gram-negative bacteria, only a fraction of this material
      reaches the medium. Recently, the gram-positive bacterium Bacillus megaterium was
      shown to efficiently secrete recombinant proteins into the growth medium. Here we
      evaluated B. megaterium for the recombinant production of antibody fragments.
      RESULTS: The lysozyme specific single chain Fv (scFv) fragment D1.3 was
      successfully produced using B. megaterium. The impact of culture medium
      composition, gene expression time and culture temperatures on the production of
      functional scFv protein was systematically analyzed. A production and secretion
      at 41 degrees C for 24 h using TB medium was optimal for this individual scFv.
      Interestingly, these parameters were very different to the optimal conditions for
      the expression of other proteins in B. megaterium. Per L culture supernatant,
      more than 400 microg of recombinant His6-tagged antibody fragment were purified
      by one step affinity chromatography. The material produced by B. megaterium
      showed an increased specific activity compared to material produced in E. coli.
      CONCLUSION: High yields of functional scFv antibody fragments can be produced and
      secreted into the culture medium by B. megaterium, making this production system
      a reasonable alternative to E. coli.

PMID- 17224046
TI  - An annotated cDNA library and microarray for large-scale gene-expression studies
      in the ant Solenopsis invicta.
AB  - Ants display a range of fascinating behaviors, a remarkable level of intra
      species phenotypic plasticity and many other interesting characteristics. Here we
      present a new tool to study the molecular mechanisms underlying these traits: a
      tentatively annotated expressed sequence tag (EST) resource for the fire ant
      Solenopsis invicta. From a normalized cDNA library we obtained 21,715 ESTs, which
      represent 11,864 putatively different transcripts with very diverse molecular
      functions. All ESTs were used to construct a cDNA microarray.

PMID- 17224055
TI  - SCF Fbx4/alphaB-crystallin cyclin D1 ubiquitin ligase: a license to destroy.
AB  - Cyclin D1 is an allosteric regulator for cyclin-dependent kinases 4 and 6
      (CDK4/6). The cyclin D/CDK4 kinase promotes G1/S transition through the
      posttranslational modification and the subsequent inactivation of the
      retinoblastoma (Rb) protein and related family members (p107 and p130).
      Accumulation of cyclin D1 is tightly regulated through various mechanisms
      including transcription, protein localization and ubiquitin-dependent
      proteolysis. While regulators of cyclin D1 gene expression have been under
      considerable scrutiny, the identity of the protein complex that targets cyclin D1
      protein for degradation, the putative E3 ubiquitin ligase, has remained obscure.
      In a recent report, Lin et al describe the identification and characterization of
      a novel SCF, wherein FBX4 and alphaB-crystallin serve as specificity factors that
      direct ubiquitination of phosphorylated cyclin D1. As cyclin D1 overexpression in
      human cancer has been postulated to occur through the loss of degradation
      machinery, the identification of the SCFFbx4/alphaB-crystallin ligase will allow
      new experimental approaches that address mechanisms of cyclin D1 overexpression
      in human cancer.

PMID- 17224054
TI  - Cognition in anxious children with attention deficit hyperactivity disorder: a
      comparison with clinical and normal children.
AB  - BACKGROUND: Cognition in children with anxiety disorders (ANX) and comorbid
      Attention Deficit Disorder (ADHD) has received little attention, potentially
      impacting clinical and academic interventions in this highly disabled group. This
      study examined several cognitive features relative to children with either pure
      condition and to normal controls. METHODS: One hundred and eight children ages 8
      12 and parents were diagnosed by semi-structured parent interview and teacher
      report as having: ANX (any anxiety disorder except OCD or PTSD; n = 52), ADHD (n
      = 21), or ANX + ADHD (n = 35). All completed measures of academic ability,
      emotional perception, and working memory. Clinical subjects were compared to 35
      normal controls from local schools. RESULTS: Groups did not differ significantly
      on age, gender, or estimated IQ. On analyses of variance, groups differed on
      academic functioning (Wide Range Achievement Test, p < .001), perception of
      emotion (auditory perception of anger, p < .05), and working memory (backwards
      digits, p < .01; backwards finger windows, p < .05; Chipasat task, p < .001). ANX
      + ADHD and children with ADHD did poorly relative to controls on all
      differentiating measures except auditory perception of anger, where ANX + ADHD
      showed less sensitivity than children with ANX or with ADHD. CONCLUSION: Though
      requiring replication, findings suggest that ANX + ADHD relates to greater
      cognitive and academic vulnerability than ANX, but may relate to reduced
      perception of anger.

PMID- 17224056
TI  - Microalbuminuria among Type 1 and Type 2 diabetic patients of African origin in
      Dar Es Salaam, Tanzania.
AB  - BACKGROUND: The prevalences and risk factors of microalbuminuria are not full
      described among black African diabetic patients. This study aimed at determining
      the prevalence of microalbuminuria among African diabetes patients in Dar es
      Salaam, Tanzania, and relate to socio-demographic features as well as clinical
      parameters. METHODS: Cross sectional study on 91 Type 1 and 153 Type 2 diabetic
      patients. Two overnight urine samples per patient were analysed. Albumin
      concentration was measured by an automated immunoturbidity assay. Average albumin
      excretion rate (AER) was used and were categorised as normalbuminuria (AER < 20
      ug/min), microalbuminuria (AER 20-200 ug/min), and macroalbuminuria (AER > 200
      ug/min). Information obtained also included age, diabetes duration, sex, body
      mass index, blood pressure, serum total cholesterol, high-density and low-density
      lipoprotein cholesterol, triglycerides, serum creatinine, and glycated hemoglobin
      A1c. RESULTS: Overall prevalence of microalbuminuria was 10.7% and
      macroalbuminuria 4.9%. In Type 1 patients microalbuminuria was 12% and
      macroalbuminuria 1%. Among Type 2 patients, 9.8% had microalbuminuria, and 7.2%
      had macroalbuminuria. Type 2 patients with abnormal albumin excretion rate had
      significantly longer diabetes duration 7.5 (0.2-24 yrs) than those with normal
      albumin excretion rate 3 (0-25 yrs), p < 0.001. Systolic and diastolic blood
      pressure among Type 2 patients with abnormal albumin excretion rate were
      significantly higher than in those with normal albumin excretion rate, (p <
      0.001). No significant differences in body mass index, glycaemic control, and
      cholesterol levels was found among patients with normal compared with those with
      elevated albumin excretion rate either in Type 1 or Type 2 patients. A stepwise
      multiple linear regression analysis among Type 2 patients, revealed AER (natural
      log AER) as the dependent variable to be predicted by [odds ratio (95% confidence
      interval)] diabetes duration 0.090 (0.049, 0.131), p < 0.0001, systolic blood
      pressure 0.012 (0.003-0.021), p < 0.010 and serum creatinine 0.021 (0.012,
      0.030). CONCLUSION: The prevalence of micro and macroalbuminuria is higher among
      African Type 1 patients with relatively short diabetes duration compared with
      prevalences among Caucasians. In Type 2 patients, the prevalence is in accordance
      with findings in Caucasians. The present study detects, however, a much lower
      prevalence than previously demonstrated in studies from sub-Saharan Africa.
      Abnormal AER was significantly related to diabetes duration and systolic blood
      pressure.

PMID- 17224057
TI  - Interpretation of multiple probe sets mapping to the same gene in Affymetrix
      GeneChips.
AB  - BACKGROUND: Affymetrix GeneChip technology enables the parallel observations of
      tens of thousands of genes. It is important that the probe set annotations are
      reliable so that biological inferences can be made about genes which undergo
      differential expression. Probe sets representing the same gene might be expected
      to show similar fold changes/z-scores, however this is in fact not the case.
      RESULTS: We have made a case study of the mouse Surf4, chosen because it is a
      gene that was reported to be represented by the same eight probe sets on the
      MOE430A array by both Affymetrix and Bioconductor in early 2004. Only five of the
      probe sets actually detect Surf4 transcripts. Two of the probe sets detect splice
      variants of Surf2. We have also studied the expression changes of the eight probe
      sets in a public-domain microarray experiment. The transcripts for Surf4 are
      correlated in time, and similarly the transcripts for Surf2 are also correlated
      in time. However, the transcripts for Surf4 and Surf2 are not correlated. This
      proof of principle shows that observations of expression can be used to confirm,
      or otherwise, annotation discrepancies. We have also investigated groups of probe
      sets on the RAE230A array that are assigned to the same LocusID, but which show
      large variances in differential expression in any one of three different
      experiments on rat. The probe set groups with high variances are found to
      represent cases of alternative splicing, use of alternative poly(A) signals, or
      incorrect annotations. CONCLUSION: Our results indicate that some probe sets
      should not be considered as unique measures of transcription, because the
      individual probes map to more than one transcript dependent upon the biological
      condition. Our results highlight the need for care when assessing whether groups
      of probe sets all measure the same transcript.

PMID- 17224058
TI  - Successful bone marrow transplantation in a patient with DNA ligase IV deficiency
      and bone marrow failure.
AB  - BACKGROUND: DNA Ligase IV deficiency syndrome is a rare autosomal recessive
      disorder caused by hypomorphic mutations in the DNA ligase IV gene (LIG4). The
      clinical phenotype shows overlap with a number of other rare syndromes, including
      Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia. Thus the
      clinical diagnosis is often delayed and established by exclusion. METHODS: We
      describe a patient with pre- and postnatal growth retardation and dysmorphic
      facial features in whom the diagnoses of Seckel-, Dubowitz-, and Nijmegen
      breakage syndrome were variably considered. Cellular radiosensitivity in the
      absence of clinical manifestations of Ataxia telangiectasia lead to the diagnosis
      of DNA ligase IV (LIG4) deficiency syndrome, confirmed by compound heterozygous
      mutations in the LIG4 gene. At age 11, after a six year history of progressive
      bone marrow failure and increasing transfusion dependency the patient was treated
      with matched sibling donor hematopoietic stem cell transplantation (HSCT) using a
      fludarabine-based conditioning regimen without irradiation. RESULTS: The post
      transplantation course was uneventful with rapid engraftment leading to complete
      and stable chimerism. Now at age 16, the patient has gained weight and is in good
      clinical condition. CONCLUSION: HSCT using mild conditioning without irradiation
      qualifies as treatment of choice in LIG4-deficient patients who have a matched
      sibling donor.

PMID- 17224059
TI  - Angiotensin type 1 receptor antagonist losartan, reduces MPTP-induced
      degeneration of dopaminergic neurons in substantia nigra.
AB  - BACKGROUND: Recent attention has focused on understanding the role of the brain
      renin-angiotensin-system (RAS) in stroke and neurodegenerative diseases. Direct
      evidence of a role for the brain-RAS in Parkinson's disease (PD) comes from
      studies demonstrating the neuroprotective effect of RAS inhibitors in several
      neurotoxin based PD models. In this study, we show that an antagonist of the
      angiotensin II (Ang II) type 1 (AT1) receptor, losartan, protects dopaminergic
      (DA) neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity
      both in primary ventral mesencephalic (VM) cultures as well as in the substantia
      nigra pars compacta (SNpc) of C57BL/6 mice (Fig. 1). RESULTS: In the presence of
      exogenous Ang II, losartan reduced MPP+ (5 muM) induced DA neuronal loss by 72%
      in vitro. Mice challenged with MPTP showed a 62% reduction in the number of DA
      neurons in the SNpc and a 71% decrease in tyrosine hydroxylase (TH)
      immunostaining of the striatum, whereas daily treatment with losartan lessened
      MPTP-induced loss of DA neurons to 25% and reduced the decrease in striatal TH+
      immunostaining to 34% of control. CONCLUSION: Our study demonstrates that the
      brain-RAS plays an important neuroprotective role in the MPTP model of PD and
      points to AT1 receptor as a potential novel target for neuroprotection.

PMID- 17224060
TI  - Feasibility of preoperative planning using anatomical facsimile models for
      mandibular reconstruction.
AB  - BACKGROUND: Functional and aesthetic mandibular reconstruction after ablative
      tumor surgery continues to be a challenge even after the introduction of
      microvascular bone transfer. Complex microvascular reconstruction of the
      resection site requires accurate preoperative planning. In the recent past, bone
      graft and fixation plates had to be reshaped during the operation by trial and
      error, often a time-consuming procedure. This paper outlines the possibilities
      and advantages of the clinical application of anatomical facsimile models in the
      preoperative planning of complex mandibular reconstructions after tumor
      resections. METHODS: From 2003 to 2005, in the Department of Maxillofacial
      Surgery of the University of Udine, a protocol was applied with the preoperative
      realization of stereolithographic models for all the patients who underwent
      mandibular reconstruction with microvascular flaps. 24 stereolithographic models
      were realized prior to surgery before emimandibulectomy or segmental
      mandibulectomy. The titanium plates to be used for fixation were chosen and bent
      on the model preoperatively. The geometrical information of the virtual
      mandibular resections and of the stereolithographic models were used to choose
      the ideal flap and to contour the flap into an ideal neomandible when it was
      still pedicled before harvesting. RESULTS: Good functional and aesthetic results
      were achieved. The surgical time was decreased on average by about 1.5 hours
      compared to the same surgical kind of procedures performed, in the same
      institution by the same surgical team, without the aforesaid protocol of
      planning. CONCLUSION: Producing virtual and stereolithographic models, and using
      them for preoperative planning substantially reduces operative time and
      difficulty of the operation during microvascular reconstruction of the mandible.

PMID- 17224061
TI  - The information sources and journals consulted or read by UK paediatricians to
      inform their clinical practice and those which they consider important: a
      questionnaire survey.
AB  - BACKGROUND: Implementation of health research findings is important for medicine
      to be evidence-based. Previous studies have found variation in the information
      sources thought to be of greatest importance to clinicians but publication in
      peer-reviewed journals is the traditional route for dissemination of research
      findings. There is debate about whether the impact made on clinicians should be
      considered as part of the evaluation of research outputs. We aimed to determine
      first which information sources are generally most consulted by paediatricians to
      inform their clinical practice, and which sources they considered most important,
      and second, how many and which peer-reviewed journals they read. METHODS: We
      inquired, by questionnaire survey, about the information sources and academic
      journals that UK medical paediatric specialists generally consulted, attended or
      read and considered important to their clinical practice. RESULTS: The same three
      information sources--professional meetings & conferences, peer-reviewed journals
      and medical colleagues--were, overall, the most consulted or attended and ranked
      the most important. No one information source was found to be of greatest
      importance to all groups of paediatricians. Journals were widely read by all
      groups, but the proportion ranking them first in importance as an information
      source ranged from 10% to 46%. The number of journals read varied between the
      groups, but Archives of Disease in Childhood and BMJ were the most read journals
      in all groups. Six out of the seven journals previously identified as containing
      best paediatric evidence are the most widely read overall by UK paediatricians,
      however, only the two most prominent are widely read by those based in the
      community. CONCLUSION: No one information source is dominant, therefore a variety
      of approaches to Continuing Professional Development and the dissemination of
      research findings to paediatricians should be used. Journals are an important
      information source. A small number of key ones can be identified and such
      analysis could provide valuable additional input into the evaluation of clinical
      research outputs.

PMID- 17224062
TI  - Walking behaviour and glycemic control in type 2 diabetes: seasonal and gender
      differences--study design and methods.
AB  - BACKGROUND: The high glucose levels typically occurring among adults with type 2
      diabetes contribute to blood vessel injury and complications such as blindness,
      kidney failure, heart disease, and stroke. Higher physical activity levels are
      associated with improved glycemic control, as measured by hemoglobin A1C. A 1%
      absolute increase in A1C is associated with an 18% increased risk for heart
      disease or stroke. Among Canadians with type 2 diabetes, we postulate that
      declines in walking associated with colder temperatures and inclement weather may
      contribute to annual post-winter increases in A1C levels. METHODS: During this
      prospective cohort study being conducted in Montreal, Quebec, Canada, 100 men and
      100 women with type 2 diabetes will undergo four assessments (once per season)
      over a one-year period of observation. These assessments include (1) use of a
      pedometer with a concealed viewing window for a two-week period to measure
      walking (2) a study centre visit during which venous blood is sampled for A1C,
      anthropometrics are assessed, and questionnaires are completed for measurement of
      other factors that may influence walking and/or A1C (e.g. food frequency,
      depressive symptomology, medications). The relationship between spring-fall A1C
      difference and winter-summer difference in steps/day will be examined through
      multivariate linear regression models adjusted for possible confounding.
      Interpretation of findings by researchers in conjunction with potential knowledge
      "users" (e.g. health professionals, patient groups) will guide knowledge
      translation efforts. DISCUSSION: Although we cannot alter weather patterns to
      favour active lifestyles, we can design treatment strategies that take seasonal
      and weather-related variations into account. For example, demonstration of
      seasonal variation of A1C levels among Canadian men and women with T2D and
      greater understanding of its determinants could lead to (1) targeting physical
      activity levels to remain at or exceed peak values achieved during more
      favourable weather conditions. Strategies may include shifting to indoor
      activities or adapting to less favourable conditions (e.g. appropriate outdoor
      garments, more frequent but shorter duration periods of activity) (2) increasing
      dose/number of glucose-lowering medications during the winter and reducing these
      during the summer, in anticipation of seasonal variations (3) examining the
      impact of bright light therapy on activity and A1C among T2D patients with an
      increase in depressive symptomology when sunlight hours decline.

PMID- 17224064
TI  - Increased cardiovascular mortality more than fifteen years after radiotherapy for
      breast cancer: a population-based study.
AB  - BACKGROUND: Breast radiotherapy as practised in the 1970s and 1980s resulted in
      significant myocardial exposure, and this was higher when the left breast was
      treated. It has been proposed that this difference might result in greater
      cardiovascular mortality following irradiation of the left breast when compared
      with the right. METHODS: All cases of female breast cancer diagnosed between 1971
      and 1988 and recorded on the Thames Cancer Registry database were followed up to
      the end of 2003 to identify cases who had died from ischaemic heart disease (IHD)
      or any cardiovascular disease (CVD). A proportional hazards regression analysis
      was performed, stratified by time since diagnosis, using as the baseline group
      those women with right-sided disease who did not receive radiotherapy, and
      adjusting for age at diagnosis. RESULTS: A total of 20,871 women with breast
      cancer were included in the analysis, of which 51% had left-sided disease.
      Mortality at 15+ years after diagnosis was increased in recipients of left-breast
      radiotherapy compared to non-irradiated women with right-sided breast cancer,
      both for IHD (hazard ratio 1.59; 95% confidence interval 1.21-2.08; p = 0.001)
      and all CVD (hazard ratio 1.27; 95% confidence interval 1.07-1.51; p = 0.006).
      When irradiated women with left-sided breast cancer were compared with irradiated
      women with right-sided breast cancer, cardiovascular mortality at 15+ years after
      diagnosis was raised by around 25% (IHD: hazard ratio 1.23; 95% confidence
      interval 0.95-1.60; p = 0.114; CVD: hazard ratio 1.25; 95% confidence interval
      1.05-1.49; p = 0.014). CONCLUSION: We have found an elevation in cardiovascular
      mortality more than 15 years after breast radiotherapy in women diagnosed with
      breast cancer between 1971 and 1988. The risk was greater following irradiation
      of the left breast compared with the right. This confirms that radiotherapy as
      practised in the 1970s and 1980s has resulted in significant long-term cardiac
      toxicity. In absolute terms, the increase in cardiovascular mortality induced by
      radiotherapy may be substantial, as these mortality events are relatively common.

PMID- 17224063
TI  - Prediction of effective genome size in metagenomic samples.
AB  - We introduce a novel computational approach to predict effective genome size
      (EGS; a measure that includes multiple plasmid copies, inserted sequences, and
      associated phages and viruses) from short sequencing reads of environmental
      genomics (or metagenomics) projects. We observe considerable EGS differences
      between environments and link this with ecologic complexity as well as species
      composition (for instance, the presence of eukaryotes). For example, we estimate
      EGS in a complex, organism-dense farm soil sample at about 6.3 megabases (Mb)
      whereas that of the bacteria therein is only 4.7 Mb; for bacteria in a nutrient
      poor, organism-sparse ocean surface water sample, EGS is as low as 1.6 Mb. The
      method also permits evaluation of completion status and assembly bias in single
      genome sequencing projects.

PMID- 17224065
TI  - Effect of polyamines and synthetic polyamine-analogues on the expression of
      antizyme (AtoC) and its regulatory genes.
AB  - BACKGROUND: In bacteria, the biosynthesis of polyamines is modulated at the level
      of transcription as well as post-translationally. Antizyme (Az) has long been
      identified as a non-competitive protein inhibitor of polyamine biosynthesis in E.
      coli. Az was also revealed to be the product of the atoC gene. AtoC is the
      response regulator of the AtoS-AtoC two-component system and it functions as the
      positive transcriptional regulator of the atoDAEB operon genes, encoding enzymes
      involved in short chain fatty acid metabolism. The antizyme is referred to as
      AtoC/Az, to indicate its dual function as both a transcriptional and post
      translational regulator. RESULTS: The roles of polyamines on the transcription of
      atoS and atoC genes as well as that of atoDAEB(ato) operon were studied.
      Polyamine-mediated induction was tested both in atoSC positive and negative E.
      coli backgrounds by using beta-galactosidase reporter constructs carrying the
      appropriate promoters patoDAEB, patoS, patoC. In addition, a selection of
      synthetic polyamine analogues have been synthesized and tested for their
      effectiveness in inducing the expression of atoC/Az, the product of which plays a
      pivotal role in the feedback inhibition of putrescine biosynthesis and the
      transcriptional regulation of the ato operon. The effects of these compounds were
      also determined on the ato operon expression. The polyamine analogues were also
      tested for their effect on the activity of ornithine decarboxylase (ODC), the key
      enzyme of polyamine biosynthesis and on the growth of polyamine-deficient E.
      coli. CONCLUSION: Polyamines, which have been reported to induce the protein
      levels of AtoC/Az in E. coli, act at the transcriptional level, since they cause
      activation of the atoC transcription. In addition, a series of polyamine
      analogues were studied on the transcription of atoC gene and ODC activity.

PMID- 17224066
TI  - Stearic acid-rich interesterified fat and trans-rich fat raise the LDL/HDL ratio
      and plasma glucose relative to palm olein in humans.
AB  - BACKGROUND: Dietary trans-rich and interesterified fats were compared to an
      unmodified saturated fat for their relative impact on blood lipids and plasma
      glucose. Each fat had melting characteristics, plasticity and solids fat content
      suitable for use as hardstock in margarine and other solid fat formulations.
      METHODS: Thirty human volunteers were fed complete, whole food diets during 4 wk
      periods, where total fat (approximately 31% daily energy, >70% from the test
      fats) and fatty acid composition were tightly controlled. A crossover design was
      used with 3 randomly-assigned diet rotations and repeated-measures analysis. One
      test fat rotation was based on palm olein (POL) and provided 12.0 percent of
      energy (%en) as palmitic acid (16:0); a second contained trans-rich partially
      hydrogenated soybean oil (PHSO) and provided 3.2 %en as trans fatty acids plus
      6.5 %en as 16:0, while the third used an interesterified fat (IE) and provided
      12.5 %en as stearic acid (18:0). After 4 wk the plasma lipoproteins, fatty acid
      profile, as well as fasting glucose and insulin were assessed. In addition, after
      2 wk into each period an 8 h postprandial challenge was initiated in a subset of
      19 subjects who consumed a meal containing 53 g of test fat. RESULTS: After 4 wk,
      both PHSO and IE fats significantly elevated both the LDL/HDL ratio and fasting
      blood glucose, the latter almost 20% in the IE group relative to POL. Fasting 4
      wk insulin was 10% lower after PHSO (p > 0.05) and 22% lower after IE (p < 0.001)
      compared to POL. For the postprandial study the glucose incremental area under
      the curve (IAUC) following the IE meal was 40% greater than after either other
      meal (p < 0.001), and was linked to relatively depressed insulin and C-peptide (p
      < 0.05). CONCLUSION: Both PHSO and IE fats altered the metabolism of lipoproteins
      and glucose relative to an unmodified saturated fat when fed to humans under
      identical circumstances.

PMID- 17224067
TI  - A strong constitutive ethylene-response phenotype conferred on Arabidopsis plants
      containing null mutations in the ethylene receptors ETR1 and ERS1.
AB  - BACKGROUND: The ethylene receptor family of Arabidopsis consists of five members,
      falling into two subfamilies. Subfamily 1 is composed of ETR1 and ERS1, and
      subfamily 2 is composed of ETR2, ERS2, and EIN4. Although mutations have been
      isolated in the genes encoding all five family members, the only previous
      insertion allele of ERS1 (ers1-2) is a partial loss-of-function mutation based on
      our analysis. The purpose of this study was to determine the extent of signaling
      mediated by subfamily-1 ethylene receptors through isolation and characterization
      of null mutations. RESULTS: We isolated new T-DNA insertion alleles of subfamily
      1 members ERS1 and ETR1 (ers1-3 and etr1-9, respectively), both of which are null
      mutations based on molecular, biochemical, and genetic analyses. Single mutants
      show an ethylene response similar to wild type, although both mutants are
      slightly hypersensitive to ethylene. Double mutants of ers1-3 with etr1-9, as
      well as with the previously isolated etr1-7, display a constitutive ethylene
      response phenotype more pronounced than that observed with any previously
      characterized combination of ethylene receptor mutations. Dark-grown etr1-9;ers1
      3 and etr1-7;ers1-3 seedlings display a constitutive triple-response phenotype.
      Light-grown etr1-9;ers1-3 and etr1-7;ers1-3 plants are dwarfed, largely sterile,
      exhibit premature leaf senescence, and develop novel filamentous structures at
      the base of the flower. A reduced level of ethylene response was still uncovered
      in the double mutants, indicating that subfamily 2 receptors can independently
      contribute to signaling, with evidence suggesting that this is due to their
      interaction with the Raf-like kinase CTR1. CONCLUSION: Our results are consistent
      with the ethylene receptors acting as redundant negative regulators of ethylene
      signaling, but with subfamily 1 receptors playing the predominant role. Loss of a
      single member of subfamily 1 is largely compensated for by the activity of the
      other member, but loss of both subfamily members results in a strong constitutive
      ethylene-response phenotype. The role of subfamily 1 members is greater than
      previously suspected and analysis of the double mutant null for both ETR1 and
      ERS1 uncovers novel roles for the receptors not previously characterized.

PMID- 17224068
TI  - From actually toxic to highly specific--novel drugs against poxviruses.
AB  - The potential use of variola virus, the causative agent of smallpox, as a
      bioweapon and the endemic presence of monkeypox virus in Africa demonstrate the
      need for better therapies for orthopoxvirus infections. Chemotherapeutic
      approaches to control viral infections have been less successful than those
      targeting bacterial infections. While bacteria commonly reproduce themselves
      outside of cells and have metabolic functions against which antibiotics can be
      directed, viruses replicate in the host cells using the cells' metabolic
      pathways. This makes it very difficult to selectively target the virus without
      damaging the host. Therefore, the development of antiviral drugs against
      poxviruses has initially focused on unique properties of the viral replication
      cycle or of viral proteins that can be selectively targeted. However, recent
      advances in molecular biology have provided insights into host factors that
      represent novel drug targets. The latest anti-poxvirus drugs are kinase
      inhibitors, which were originally developed to treat cancer progression but in
      addition block egress of poxviruses from infected cells. This review will
      summarize the current understanding of anti-poxvirus drugs and will give an
      overview of the development of the latest second generation poxvirus drugs.

PMID- 17224069
TI  - Use of patient flow analysis to improve patient visit efficiency by decreasing
      wait time in a primary care-based disease management programs for anticoagulation
      and chronic pain: a quality improvement study.
AB  - BACKGROUND: Patients with chronic conditions require frequent care visits.
      Problems can arise during several parts of the patient visit that decrease
      efficiency, making it difficult to effectively care for high volumes of patients.
      The purpose of the study is to test a method to improve patient visit efficiency.
      METHODS: We used Patient Flow Analysis to identify inefficiencies in the patient
      visit, suggest areas for improvement, and test the effectiveness of clinic
      interventions. RESULTS: At baseline, the mean visit time for 93 anticoagulation
      clinic patient visits was 84 minutes (+/- 50 minutes) and the mean visit time for
      25 chronic pain clinic patient visits was 65 minutes (+/- 21 minutes). Based on
      these data, we identified specific areas of inefficiency and developed
      interventions to decrease the mean time of the patient visit. After
      interventions, follow-up data found the mean visit time was reduced to 59 minutes
      (+/-25 minutes) for the anticoagulation clinic, a time decrease of 25 minutes (t
      test 39%; p < 0.001). Mean visit time for the chronic pain clinic was reduced to
      43 minutes (+/- 14 minutes) a time decrease of 22 minutes (t-test 34 %; p <
      0.001). CONCLUSION: Patient Flow Analysis is an effective technique to identify
      inefficiencies in the patient visit and efficiently collect patient flow data.
      Once inefficiencies are identified they can be improved through brief
      interventions.

PMID- 17224070
TI  - Schwannoma of the external auditory canal: a case report.
AB  - BACKGROUND: Schwannomas are uncommon benign tumors of the external auditory
      canal. The clinical features, the differential diagnosis, and the surgical
      treatment of these lesions are discussed. CASE PRESENTATION: A 51-year-old
      patient presented with a mass obliterating the external auditory meatus.
      Excisional biopsy was performed. Diagnosis was reported to be schwannoma by
      histopathologic examination. CONCLUSION: Schwannoma, rarely seen in the external
      auditory canal, can be managed by a precise excision of the tumor via transmeatal
      approach.

PMID- 17224071
TI  - The PB1-F2 protein of Influenza A virus: increasing pathogenicity by disrupting
      alveolar macrophages.
AB  - With the prospect of another pandemic Influenza fresh in our consciousness, the
      pathogenic nature of the Influenza A virus and its ability to induce high rates
      of mortality are ever more pertinent. Recently a novel protein encoded by an
      alternate reading frame in the PB1 Gene segment of Influenza A virus has been
      discovered and in turn shown to enhance viral virulence in a mouse model 1. This
      protein has been shown to specifically target and destroy alveolar macrophages 2.
      This review suggests that this protein, present in all previous pandemic strains,
      may reappear as a virulence factor in a subsequent pandemic strain. This PB1-F2
      protein will enhance the mortality rate of the virus by increasing the likelihood
      of a secondary bacterial infection, which is the primary cause of death to a
      patient infected with Influenza A.

PMID- 17224072
TI  - Intensity modulated radiotherapy for localized prostate cancer: rigid compliance
      to dose-volume constraints as a warranty of acceptable toxicity?
AB  - BACKGROUND: To report the toxicity after intensity modulated radiotherapy (IMRT)
      for patients with localized prostate cancer, as a sole treatment or after radical
      prostatectomy. METHODS: Between August 2001 and December 2003, 132 patients with
      prostate cancer were treated with IMRT and 125 were evaluable to acute and late
      toxicity analysis, after a minimum follow-up time of one year. Clinical and
      treatment data, including normal tissue dose-volume histogram (DVH) constraints,
      were reviewed. Gastro-intestinal (GI) and genito-urinary (GU) signs and symptoms
      were evaluated according to the Radiation Therapy Oncology Group (RTOG) toxicity
      scales. Median prescribed dose was 76 Gy. Median follow-up time was of 26.1
      months. RESULTS: From the 125 patients, 73 (58.4%) presented acute Grade 1 or
      Grade 2 GI and 97 (77.2%) presented acute Grade 1 or Grade 2 GU toxicity. Grade 3
      GI acute toxicity occurred in only 2 patients (1.6%) and Grade 3 GU acute
      toxicity in only 3 patients (2.4%). Regarding Grade 1 and 2 late toxicity, 26
      patients (20.8%) and 21 patients (16.8%) presented GI and GU toxicity,
      respectively. Grade 2 GI late toxicity occurred in 6 patients (4.8%) and Grade 2
      GU late toxicity in 4 patients (3.2%). None patient presented any Grade 3 or
      higher late toxicity. Non-conformity to DVH constraints occurred in only 11.2% of
      treatment plans. On univariate analysis, no significant risk factor was
      identified for Grade 2 GI late toxicity, but mean dose delivered to the PTV was
      associated to higher Grade 2 GU late toxicity (p = 0.042). CONCLUSION: IMRT is a
      well tolerable technique for routine treatment of localized prostate cancer, with
      short and medium-term acceptable toxicity profiles. According to the data
      presented here, rigid compliance to DHV constraints might prevent higher
      incidences of normal tissue complication.

PMID- 17224073
TI  - Primary retroperitoneal mucinous cystadenocarcinoma: report of two cases.
AB  - BACKGROUND: Retroperitoneal cystadenocarcinomas are rare lesions, the majority of
      cases presented as one-patient reports. METHODS: We present two cases of
      retroperitoneal cystadenocarcinoma, both in women of reproductive age: one with
      aggressive behavior, and the remaining case, with a more indolent clinical
      evolution. RESULTS: One case presented as pelvic tumor, was treated with surgical
      resection of the disease, but manifested with recurrent disease a few months
      later despite use of chemotherapy. The second case involved a patient with
      diagnosis of abdominal tumor; during laparotomy, a retroperitoneal tumor was
      found and was totally removed. At follow-up, the patient is disease-free with no
      other treatment. CONCLUSION: The behavior and treatment of retroperitoneal
      cystadenocarcinoma are controversial. We suggest aggressive surgery including
      radical hysterectomy and bilateral salpingoopherectomy with adjuvant chemotherapy
      in these cases.

PMID- 17224074
TI  - Somatic sequence alterations in twenty-one genes selected by expression profile
      analysis of breast carcinomas.
AB  - INTRODUCTION: Genomic alterations have been observed in breast carcinomas that
      affect the capacity of cells to regulate proliferation, signaling, and
      metastasis. Re-sequence studies have investigated candidate genes based on prior
      genetic observations (changes in copy number or regions of genetic instability)
      or other laboratory observations and have defined critical somatic mutations in
      genes such as TP53 and PIK3CA. METHODS: We have extended the paradigm and
      analyzed 21 genes primarily identified by expression profiling studies, which are
      useful for breast cancer subtyping and prognosis. This study conducted a
      bidirectional re-sequence analysis of all exons and 5', 3', and evolutionarily
      conserved regions (spanning more than 16 megabases) in 91 breast tumor samples.
      RESULTS: Eighty-seven unique somatic alterations were identified in 16 genes.
      Seventy-eight were single base pair alterations, of which 23 were missense
      mutations; 55 were distributed across conserved intronic regions or the 5' and 3'
      regions. There were nine insertion/deletions. Because there is no a priori way to
      predict whether any one of the identified synonymous and noncoding somatic
      alterations disrupt function, analysis unique to each gene will be required to
      establish whether it is a tumor suppressor gene or whether there is no effect. In
      five genes, no somatic alterations were observed. CONCLUSION: The study confirms
      the value of re-sequence analysis in cancer gene discovery and underscores the
      importance of characterizing somatic alterations across genes that are related
      not only by function, or functional pathways, but also based upon expression
      patterns.

PMID- 17224077
TI  - An open access journal of molecular signaling: a critical need at a critical
      time.
AB  - Molecular signaling is an exponentially growing field that encompasses different
      molecular aspects of cell signaling underlying normal and pathological
      conditions. This area also focuses on defining the genetic and epigenetic changes
      that modulate the signaling properties of cells and the resultant physiological
      as well as pathological conditions. Therefore, rapid publication of results from
      these endeavors and, more importantly, free access to such publications can truly
      accelerate the progress in this field leading to the development of novel
      targeted drugs. With this goal in mind, Journal of Molecular Signaling, a journal
      fully devoted to open access publishing of rigorously peer-reviewed quality
      manuscripts in the molecular signaling area of research, is being launched. The
      focus, significance, and, the open access model of publishing of Journal of
      Molecular Signaling are discussed.

PMID- 17224075
TI  - High glucose upregulates connective tissue growth factor expression in human
      vascular smooth muscle cells.
AB  - BACKGROUND: Connective tissue growth factor (CTGF) is a potent profibrotic
      factor, which is implicated in fibroblast proliferation, angiogenesis and
      extracellular matrix (ECM) synthesis. It is a downstream mediator of some of the
      effects of transforming growth factor beta (TGFbeta) and is potentially induced
      by hyperglycemia in human renal mesangial cells. However, whether high glucose
      could induce the CTGF expression in vascular smooth muscle cells (VSMCs) remains
      unknown. Therefore, this study was designed to test whether high glucose could
      regulate CTGF expression in human VSMC. The effect of modulating CTGF expression
      on VSMC proliferation and migration was further investigated. RESULTS: Expression
      of CTGF mRNA was up-regulated as early as 6 hours in cultured human VSMCs after
      exposed to high glucose condition, followed by ECM components (collagen type I
      and fibronectin) accumulation. The upregulation of CTGF mRNA appears to be
      TGFbeta-dependent since anti-TGFbeta antibody blocks the effect of high glucose
      on CTGF gene expression. A small interference RNA (siRNA) targeting CTGF mRNA
      (CTGF-siRNA) effectively suppressed CTGF up-regulation stimulated by high glucose
      up to 79% inhibition. As a consequence of decreased expression of CTGF gene, the
      deposition of ECM proteins in the VSMC was also declined. Moreover, CTGF-siRNA
      expressing vector partially inhibited the high glucose-induced VSMC proliferation
      and migration. CONCLUSION: Our data suggest that in the development of
      macrovascular complications in diabetes, CTGF might be an important factor
      involved in the patho-physiological responses to high glucose in human VSMCs. In
      addition, the modulatory effects of CTGF-siRNA during this process suggest that
      specific targeting CTGF by RNA interference could be useful in preventing intimal
      hyperplasia in diabetic macrovascular complications.

PMID- 17224078
TI  - Differential partitioning of Galphai1 with the cellular microtubules: a possible
      mechanism of development of Taxol resistance in human ovarian carcinoma cells.
AB  - BACKGROUND: Taxol binds to the cellular microtubules and suppresses their dynamic
      instability. Development of tumor cell resistance to taxol is typically
      associated with increased expression of the drug efflux pump P-glycoprotein
      and/or alterations in the microtubules. Recently, changes in the dynamic
      instability of the microtubules have also been associated with development of
      taxol resistance in a lung cancer cell line. We have established a 250-fold taxol
      resistant human ovarian carcinoma subline (2008/13/4) that does not display the
      typical alterations associated with development of drug resistance. RESULTS:
      Utilizing the mRNA differential display technique, we observed increased
      expression of an alpha subunit of the guanine nucleotide-binding protein,
      Galphai1, in the taxol-resistant human ovarian carcinoma cell lines compared to
      the parental 2008 cells. Several isoforms of the alpha-subunit of the G protein
      have been identified and the Galphai (inhibitory) are so named because they
      inhibit the activity of adenylate cyclase leading to inactivation of the cAMP
      dependent protein kinase A (PKA) pathway. In addition, Galphai1 is also known to
      bind to microtubules and activates their GTPase activity and thus induces
      depolymerization of the microtubules. In the present study we demonstrate that
      the intracellular level of cAMP and the PKA activity were higher in the taxol
      resistant 2008/13/4 and the 2008/17/4 cells despite the increased expression of
      Galphai1 in these cells. Moreover, Galphai1 was found to be localized not on the
      cell membrane, but in intracellular compartments in both the taxol-sensitive and 
      resistant human ovarian carcinoma cells. Interestingly, increased association of
      the Galphai1 protein and the microtubules in the taxol-resistant cells compared
      to the parental 2008 cells was observed, both prior to and after treatment of
      these cells with taxol. CONCLUSION: Based on the opposing effects of taxol and
      the Galphai1 protein on the microtubule dynamic instability (taxol suppresses
      microtubule dynamic instability whilst the Galphai1 protein inhibits the
      suppression) our results indicate the operation of a novel pathway that would
      enable the cells to escape the cytotoxic effects of taxol.

PMID- 17224076
TI  - CD4/CD8 ratio and cytokine levels of the BAL fluid in patients with
      bronchiectasis caused by sulfur mustard gas inhalation.
AB  - OBJECTIVE: To analyze cytokine levels in BAL fluid of patients with
      bronchiectasis due to mustard gas inhalation. PATIENTS: 29 victims with mustard
      gas-induced bronchiectasis and 25 normal veterans as control group. INTERVENTION:
      PFTs,, high-resolution CT scans of the chest, analyses of BAL fluids for five
      cytokines (IL-8, IL-1beta, IL-6, TNF-alpha, IL-12) and analyses of BAL fluids for
      cellular and flow-cytometric analysis of the phenotype of bronchoalveolar cells
      were performed in all cases. RESULTS: CD4 lymphocytes expressed as percentage or
      absolute number were significantly higher in patients with bronchiectasis than in
      controls (32.17 +/- 16.00 vs 23.40 +/- 6.97%, respectively; p = 0.01; and 3.31 +/
      2.03 vs 1.88 +/- 0.83 x 10(3) cells/ml, respectively; p = 0.001). The CD4/CD8
      ratio was significantly higher in patients with bronchiectasis than in controls
      (3.08 +/- 2.05 vs 1.68 +/- 0.78; p = 0.002). There were significant differences
      in cytokine (IL-8, IL-1beta, IL-6, TNF-alpha, IL-12) levels of BAL fluid between
      patients with bronchiectasis and healthy controls.A significant correlation was
      observed between the HRCT scores and both the percentage and the absolute number
      of CD4 lymphocytes in BAL fluid in patients with bronchiectasis (r = -0.49, p =
      0.009; r = -0.50, p = 0.008; respectively). HRCT scores showed a significant
      correlation with CD4/CD8 ratios (r = 0.54, p = 0.004) too. Of measured BAL
      cytokines, only IL-8 (r = -0.52, p = 0.005) and TNF-aalpha (r = 0.44, p = 0.01)
      showed significant correlations with the HRCT scores. CONCLUSION: The increased
      levels of cytokines CD4 lymphocytes in the BAL fluid suggest the possible
      causative mechanism in the lung in sulfur mustard gas-induced bronchiectasis by
      the recruitment of neutrophils into the lung.

PMID- 17224079
TI  - Yeast Ste2 receptors as tools for study of mammalian protein kinases and adaptors
      involved in receptor trafficking.
AB  - BACKGROUND: Mammalian receptors that couple to effectors via heterotrimeric G
      proteins (e.g., beta 2-adrenergic receptors) and receptors with intrinsic
      tyrosine kinase activity (e.g., insulin and IGF-I receptors) constitute the
      proximal points of two dominant cell signaling pathways. Receptors coupled to G
      proteins can be substrates for tyrosine kinases, integrating signals from both
      pathways. Yeast cells, in contrast, display G protein-coupled receptors (e.g.,
      alpha-factor pheromone receptor Ste2) that have evolved in the absence of
      receptor tyrosine kinases, such as those found in higher organisms. We sought to
      understand the motifs in G protein-coupled receptors that act as substrates for
      receptor tyrosine kinases and the functional consequence of such phosphorylation
      on receptor biology. We expressed in human HEK 293 cells yeast wild-type Ste2 as
      well as a Ste2 chimera engineered with cytoplasmic domains of the beta2
      adrenergic receptor and tested receptor sequestration in response to activation
      of the insulin receptor tyrosine kinase. RESULTS: The yeast Ste2 was successfully
      expressed in HEK 293 cells. In response to alpha-factor, Ste2 signals to the
      mitogen-activated protein kinase pathway and internalizes. Wash out of agonist
      and addition of antagonist does not lead to Ste2 recycling to the cell membrane.
      Internalized Ste2 is not significantly degraded. Beta2-adrenergic receptors
      display internalization in response to agonist (isoproterenol), but rapidly
      recycle to the cell membrane following wash out of agonist and addition of
      antagonist. Beta2-adrenergic receptors display internalization in response to
      activation of insulin receptors (i.e., cross-regulation), whereas Ste2 does not.
      Substitution of the cytoplasmic domains of the beta2-adrenergic receptor for
      those of Ste2 creates a Ste2/beta2-adrenergic receptor chimera displaying insulin
      stimulated internalization. CONCLUSION: Chimera composed of yeast Ste2 into which
      domains of mammalian G protein-coupled receptors have been substituted, when
      expressed in animal cells, provide a unique tool for study of the regulation of G
      protein-coupled receptor trafficking by mammalian receptor tyrosine kinases and
      adaptor proteins.

PMID- 17224080
TI  - Tyrosine-specific MAPK phosphatases and the control of ERK signaling in PC12
      cells.
AB  - BACKGROUND: Spatio-temporal control of extracellular signal-regulated kinase
      (ERK) activity, a critical determinant of the cell's response to growth factors,
      requires timely dephosphorylation of its regulatory tyrosine and/or threonine
      residue by MAPK phosphatases. We studied the physiological role of kinase
      interaction motif (KIM)-containing protein tyrosine phosphatases (PTPs) in the
      control of EGF- and NGF-induced ERK activity in neuroendocrine PC12 cells.
      RESULTS: We found a single KIM-containing PTP to be endogenously expressed in rat
      PC12 cells: the transmembrane PTPRR isoform termed PCPTP1. Protein knock-down of
      PCPTP1, or fourfold overexpression of its mouse orthologue, PTPBR7, left EGF- and
      NGF-induced ERK1/2 activity in PC12 cells unaltered. Ectopic expression of
      cytosolic PTPRR isoforms, however, resulted in reduced EGF-induced ERK1/2
      activity, an effect that was dependent on the phosphatase activity and the KIM
      domain of these PTPs. CONCLUSION: The finding that robust changes in tyrosine
      specific MAPK phosphatase expression levels have minor effects on temporal ERK1/2
      activity control in PC12 cells suggests that dual-specificity MAPK phosphatases
      may act as major regulators of growth factor-induced ERK1/2 signaling in these
      cells.

PMID- 17224081
TI  - Estradiol effects on the dopamine transporter - protein levels, subcellular
      location, and function.
AB  - BACKGROUND: The effects of estrogens on dopamine (DA) transport may have
      important implications for the increased incidence of neurological disorders in
      women during life stages when hormonal fluctuations are prevalent, e.g. during
      menarche, reproductive cycling, pregnancy, and peri-menopause. RESULTS: The
      activity of the DA transporter (DAT) was measured by the specific uptake of 3H
      DA. We found that low concentrations (10(-14) to 10(-8) M) of 17beta-estradiol
      (E2) inhibit uptake via the DAT in PC12 cells over 30 minutes, with significant
      inhibition taking place due to E2 exposure during only the last five minutes of
      the uptake period. Such rapid action suggests a non-genomic, membrane-initiated
      estrogenic response mechanism. DAT and estrogen receptor-alpha (ERalpha) were
      elevated in cell extracts by a 20 ng/ml 2 day NGFbeta treatment, while ERbeta was
      not. DAT, ERalpha and ERbeta were also detectable on the plasma membrane of
      unpermeabilized cells by immunocytochemical staining and by a fixed cell,
      quantitative antibody (Ab)-based plate assay. In addition, PC12 cells contained
      RNA coding for the alternative membrane ER GPR30; therefore, all 3 ER subtypes
      are candidates for mediating the rapid nongenomic actions of E2. At cell
      densities above 15,000 cells per well, the E2-induced inhibition of transport was
      reversed. Uptake activity oscillated with time after a 10 nM E2 treatment; in a
      slower room temperature assay, inhibition peaked at 9 min, while uptake activity
      increased at 3 and 20-30 min. Using an Ab recognizing the second extracellular
      loop of DAT (accessible only on the outside of unpermeabilized cells), our
      immunoassay measured membrane vs. intracellular/nonvesicular DAT; both were found
      to decline over a 5-60 min E2 treatment, though immunoblot analyses demonstrated
      no total cellular loss of protein. CONCLUSION: Our results suggest that
      physiological levels of E2 may act to sequester DAT in intracellular compartments
      where the transporter's second extramembrane loop is inaccessible (inside
      vesicles) and that rapid estrogenic actions on this differentiated neuronal cell
      type may be regulated via membrane ERs of several types.

PMID- 17224082
TI  - Amino terminal tyrosine phosphorylation of human MIXL1.
AB  - Seven members of the Mix family of paired-type homeoproteins regulate
      mesoderm/endoderm differentiation in amphibians. In mammals, the MIXL1 (Mix. 1
      homeobox [Xenopus laevis]-like gene 1) gene is the sole representative of this
      family. Unlike the amphibian Mix genes that encode an open reading frame of >300
      amino acids, mammalian MIXL1 encodes a smaller protein (approximately 230aa).
      However, mammalian MIXL1 contains a unique proline-rich domain (PRD) with a
      potential to interact with signal transducing Src homolgy 3 (SH3) domains.
      Notably, human MIXL1 also contains a unique tyrosine residue Tyr20 that is amino
      terminal to the PRD. Here we report that mammalian MIXL1 protein is
      phosphorylated at Tyr20 and the phosphorylation is dramatically reduced in the
      absence of PRD. Our findings are consistent with Tyr20 phosphorylation of MIXL1
      being a potential regulatory mechanism that governs its activity.

PMID- 17224083
TI  - Rac inhibits thrombin-induced Rho activation: evidence of a Pak-dependent GTPase
      crosstalk.
AB  - The strict spatio-temporal control of Rho GTPases is critical for many cellular
      functions, including cell motility, contractility, and growth. In this regard,
      the prototypical Rho family GTPases, Rho, Rac, and Cdc42 regulate the activity of
      each other by a still poorly understood mechanism. Indeed, we found that
      constitutively active forms of Rac inhibit stress fiber formation and Rho
      stimulation by thrombin. Surprisingly, a mutant of Rac that is unable to activate
      Pak1 failed to inhibit thrombin signaling to Rho. To explore the underlying
      mechanism, we investigated whether Pak1 could regulate guanine nucleotide
      exchange factors (GEFs) for Rho. We found that Pak1 associates with P115-RhoGEF
      but not with PDZ-RhoGEF or LARG, and knock down experiments revealed that P115
      RhoGEF plays a major role in signaling from thrombin receptors to Rho in HEK293T
      cells. Pak1 binds the DH-PH domain of P115-RhoGEF, thus suggesting a mechanism by
      which Rac stimulation of Pak1 may disrupt receptor-dependent Rho signaling. In
      agreement, expression of a dominant-negative Pak-Inhibitory Domain potentiated
      the activation of Rho by thrombin, and prevented the inhibition of Rho by Rac.
      These findings indicate that Rac interferes with receptor-dependent Rho
      stimulation through Pak1, thus providing a mechanism for cross-talk between these
      two small-GTPases.

PMID- 17224084
TI  - Agonist mediated internalization of M2 mAChR is beta-arrestin-dependent.
AB  - BACKGROUND: Muscarinic acetylcholine receptors (mAChRs) undergo agonist-promoted
      internalization, but evidence suggesting that the mechanism of internalization is
      beta-arrestin dependent has been contradictory and unclear. Previous studies
      using heterologous over-expression of wild type or dominant-negative forms of
      beta-arrestins have reported that agonist-promoted internalization of M2 mAChRs
      is a beta-arrestin- and clathrin-independent phenomenon. In order to circumvent
      the complications associated with the presence of endogenous beta-arrestin that
      may have existed in these earlier studies, we examined agonist-promoted
      internalization of the M2 mAChR in mouse embryonic fibroblasts (MEFs) derived
      from beta-arrestin knockout mice that lack expression of either one or both
      isoforms of beta-arrestin (beta-arrestin 1 and 2). RESULTS: In wild type MEF
      cells transiently expressing M2 mAChRs, 40% of surface M2 mAChRs underwent
      internalization and sorted into intracellular compartments following agonist
      stimulation. In contrast, M2 mAChRs failed to undergo internalization and sorting
      into intracellular compartments in MEF beta-arrestin double knockout cells
      following agonist stimulation. In double knockout cells, expression of either
      beta-arrestin 1 or 2 isoforms resulted in rescue of agonist-promoted
      internalization. Stimulation of M2 mAChRs led to a stable co-localization with
      GFP-tagged beta-arrestin within endocytic structures in multiple cell lines; the
      compartment to which beta-arrestin localized was determined to be the early
      endosome. Agonist-promoted internalization of M2 mAChRs was moderately rescued in
      MEF beta-arrestin 1 and 2 double knockout cells expressing exogenous arrestin
      mutants that were selectively defective in interactions with clathrin (beta
      arrestin 2 DeltaLIELD), AP-2 (beta-arrestin 2-F391A), or both clathrin/AP-2.
      Expression of a truncated carboxy-terminal region of beta-arrestin 1 (319-418)
      completely abrogated agonist-promoted internalization of M2 mAChRs in wild type
      MEF cells. CONCLUSION: In summary, this study demonstrates that agonist-promoted
      internalization of M2 mAChRs is beta-arrestin- and clathrin-dependent, and that
      the receptor stably co-localizes with beta-arrestin in early endosomal vesicles.

PMID- 17224085
TI  - Modelling the epidemiology and transmission of Verocytotoxin-producing
      Escherichia coli serogroups O26 and O103 in two different calf cohorts.
AB  - Mathematical models are constructed to investigate the population dynamics of
      Verocytotoxin-producing Escherichia coli (VTEC) serogroups O26 and O103 in two
      different calf cohorts. We compare the epidemiological characteristics of these
      two serogroups within the same calf cohort as well as the same serogroups between
      the two calf cohorts. The sources of infection are quantified for both calf
      cohort studies. VTEC serogroups O26 and O103 mainly differ in the rate at which
      calves acquire infection from sources other than infected calves, while infected
      calves typically remain infectious for less than 1 week regardless of the
      serogroups. Fewer than 20% of VTEC-positive samples are the result of calf-to
      calf transmission. PFGE typing data are available for VTEC-positive samples to
      further subdivide the serogroup data in one of the two calf cohort studies. For
      serogroup O26 but not O103, there is evidence for unequal environmental exposure
      to infection with different PFGE types.

PMID- 17224086
TI  - A survey of zoonotic pathogens carried by Norway rats in Baltimore, Maryland,
      USA.
AB  - Norway rats (Rattus norvegicus) carry several zoonotic pathogens and because rats
      and humans live in close proximity in urban environments, there exists potential
      for transmission. To identify zoonotic agents carried by rats in Baltimore,
      Maryland, USA, we live-trapped 201 rats during 2005-2006 and screened them for a
      panel of viruses, bacteria, and parasites. Antibodies against Seoul virus
      (57.7%), hepatitis E virus (HEV, 73.5%), Leptospira interrogans (65.3%),
      Bartonella elizabethae (34.1%), and Rickettsia typhi (7.0%) were detected in
      Norway rats. Endoparasites, including Calodium hepatica (87.9%) and Hymenolepis
      sp. (34.4%), and ectoparasites (13.9%, primarily Laelaps echidninus) also were
      present. The risk of human exposure to these pathogens is a significant public
      health concern. Because these pathogens cause non-specific and often self
      limiting symptoms in humans, infection in human populations is probably
      underdiagnosed.

PMID- 17224087
TI  - Incidence of cryptosporidiosis species in paediatric patients in Malawi.
AB  - We determined the incidence of cryptosporidiosis in children aged <5 years
      presenting with diarrhoea in an urban and rural hospital-based setting in Malawi.
      Stools were collected over a 22-month period during both rainy and dry seasons. A
      range of microscopic methods were used to determine the presence of
      Cryptosporidium spp. oocysts. Species determination was by polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) of oocyst-extracted
      DNA using 18S rRNA and COWP gene loci. Cryptosporidium spp. oocysts were seen in
      5.9% (50/848) of samples, of which 43 amplified by PCR-RFLP indicated the
      following species: C. hominis, C. parvum, C. hominis/C. parvum, C. meleagridis
      and C. andersoni. Seven samples could not be amplified by PCR. Wider species
      diversity was found in the rural setting, and may be a result of increased
      malnutrition and zoonotic exposure in this area. Improvements in water,
      sanitation, household hygiene and animal control are required to reduce the
      incidence of infection in this population.

PMID- 17224088
TI  - The magnitude and distribution of infectious intestinal disease in Malta: a
      population-based study.
AB  - Routine sources of information on infectious intestinal disease (IID) capture a
      fraction of the actual disease burden. Population studies are required to measure
      the burden of illness. A retrospective age-stratified cross-sectional telephone
      study was carried out in Malta in order to estimate the magnitude and
      distribution of IID at population level. A random sample of 3504 persons was
      interviewed by a structured questionnaire between April 2004 and December 2005.
      The response rate was 99.7%. From the study, the observed standardized monthly
      prevalence was 3.18% (95% CI 0.7-5.74) with 0.421 (95% CI 0.092-0.771) episodes
      of IID per person per year. The monthly prevalence was higher in the <5 years age
      group and in females aged 31-44 years. The mean duration of illness was 6.8 days
      and a median duration of 3 days. A bimodal seasonal distribution was observed
      with peaks in June-July and October-November.

PMID- 17224089
TI  - Effects of gradual discontinuation of selective serotonin reuptake inhibitors in
      panic disorder with agoraphobia.
AB  - The aim of this investigation was to explore the prevalence and features of
      discontinuation syndromes ensuing with gradual tapering of selective serotonin
      reuptake inhibitors (SSRIs), in optimal clinical conditions in patients with
      panic disorder and agoraphobia. Twenty-six consecutive outpatients met the DSM-IV
      criteria for panic disorder and agoraphobia while taking SSRIs. Twenty remitted
      upon behavioural treatment. Antidepressant drugs were then tapered at the slowest
      possible pace and with appropriate patient education. Patients were assessed with
      the Discontinuation-Emergent Signs and Symptoms (DESS) checklist 2 wk, 1 month
      and 1 yr after discontinuation. Nine of the 20 patients (45%) experienced a
      discontinuation syndrome, which subsided within a month in all but three patients
      who had been taking paroxetine for a long time. Discontinuation syndromes
      appeared to be fairly common even when performed with slow tapering and during
      clinical remission. In some cases disturbances persisted for months after
      discontinuation.

PMID- 17224091
TI  - Experimental manipulation of cognitive control processes causes an increase in
      communication disturbances in healthy volunteers.
AB  - BACKGROUND: Although communication disturbances (CD) have been associated with
      poor cognitive control, it is unclear whether they are associated specifically
      with poor cognitive control or with poor cognition in general. The current
      research examined whether (a) two specific components of cognitive control,
      working memory and interference resolution, were associated with CD, and (b)
      associations between CD and cognitive control could be accounted for by
      generalized poor cognitive performance. METHOD: In this study, as healthy
      volunteers spoke, the level of cognitive demands was experimentally increased,
      thereby simulating cognitive deficits (i.e. a reduction in the degree to which
      certain types of cognitive processes could be used for speech). Hence, this
      research examined whether simulated cognitive deficits would cause an increase in
      CD. Participants also completed separate cognitive tasks that assessed working
      memory, interference resolution and general cognitive ability. RESULTS: An
      increase in working memory demands caused an increase in CD. Moreover, working
      memory demands interacted with interference resolution demands, with the greatest
      amount of CD caused by both high working memory and high interference resolution
      demands. By contrast, increasing another cognitive demand, sustained attention,
      did not increase CD. Furthermore, performance on separate working memory and
      interference resolution tasks interacted to predict CD on the experimental speech
      task. However, performance on a psychometrically matched cognitive task did not
      predict CD. CONCLUSION: Overall, the current study provides evidence that working
      memory and interference resolution may be specifically associated with CD and
      that manipulations of these cognitive control processes can cause an increase in
      CD.

PMID- 17224090
TI  - Nasopharyngeal dimensions in magnetic resonance imaging and the risk of acute
      otitis media.
AB  - BACKGROUND: We have previously found by lateral cephalometry an association
      between nasopharyngeal anatomy and the risk of acute otitis media (AOM). We
      evaluate here the association of nasopharyngeal dimensions in magnetic resonance
      imaging (MRI) with the occurrence of AOM in otherwise healthy children. METHODS:
      Sixty-one healthy children (mean age 5.7 years, range 3.9-6.9) were recruited
      from child care centres. The parents filled in a questionnaire on the child's
      history of ear infections and adenoidectomy. MRI was performed with a 4 mm slice
      thickness during an upper respiratory infection. Five dimensions and two angles
      expressing the structure of the bony nasopharynx were measured in sagittal
      images. RESULTS: The dimension from the caudal edge of the septum to the midpoint
      of the sella, reflecting the height of the nasopharynx, was on average 2.2 mm
      smaller in the children who had had AOM attacks during the last 12 months than
      those without attacks (95% confidence interval (CI) 0.9 to 3.4, p=0.001) and the
      nasal base angle was on average 2.1 degrees smaller (95% CI 0.7 to 3.5, p=0.004).
      These differences remained significant after adjustment for age, sex and previous
      adenoidectomy in the logistic modelling. A history of adenoidectomy did not have
      any effect on the dimensions. CONCLUSIONS: The nasopharynx was smaller in the
      children with AOM attacks during the last year. The value of this finding for
      predicting susceptibility to recurrent AOM and directing preventive procedures
      should be evaluated.

PMID- 17224092
TI  - Genetic overlap between bipolar illness and event-related potentials.
AB  - BACKGROUND: Electrophysiological endophenotypes are far less explored in bipolar
      disorder as compared to schizophrenia. No previous twin study of event-related
      potentials (ERPs) in bipolar illness has been reported. This study uses a twin
      design and advanced genetic model fitting analyses aiming to (1) assess and
      quantify the relationship of a range of ERP components with bipolar disorder with
      psychotic features, and (2) examine the source of the relationship (due to
      genetic or environmental factors). METHOD: P300, P50 suppression and mismatch
      negativity (MMN) were recorded in 10 discordant monozygotic (MZ) bipolar twin
      pairs, six concordant MZ bipolar twin pairs and 78 control twin pairs.
      Statistical analyses were based on structural equation modelling. RESULTS:
      Bipolar disorder was significantly associated with smaller P300 amplitude and
      decreased P50 suppression. Genetic correlations were the main source of the
      associations, estimated to be -0 x 33 for P300 amplitude and 0 x 46 for P50
      ratio. Individual-specific environmental influences were not significant. MMN and
      P300 latency were not associated with the illness. CONCLUSIONS: The results
      provide supporting evidence that P300 amplitude and P50 suppression ratio are ERP
      endophenotypes for bipolar disorder.

PMID- 17224093
TI  - Corpus callosum areas in first-episode patients with bipolar disorder.
AB  - BACKGROUND: Morphological changes in the corpus callosum (CC) have been described
      in bipolar disorder, but with inconsistencies among the reports. We investigated
      the CC areas by magnetic resonance imaging (MRI) in 12 first-episode patients
      with bipolar disorder and 12 controls. METHOD: Twelve medication-naive patients
      with bipolar I disorder (six males, six females; aged 28 x 2+/-6 x 5 years) with
      manic or mixed episodes and 12 age- and gender-matched healthy controls (six
      males, six females; aged 26 x 8+/-7 x 6 years) were recruited to the study. MRI
      scans was obtained using a 1.5-T GE Signa Excite high-speed scanner. Anatomical
      measurements were conducted on a computer workstation with the software Scion
      Image Beta-3b for Windows. Statistical analysis was performed using an analysis
      of covariance (ANCOVA), the t test, chi2 and partial correlation analyses.
      RESULTS: Bipolar patients had significantly smaller areas of total CC, anterior
      body posterior body and isthmus compared with healthy control subjects by ANCOVA,
      with age, gender and intracranial volume (ICV) as covariates. There was a
      negative correlation between total CC, posterior body and isthmus areas and Young
      Mania Rating Scale (YMRS) scores. CONCLUSION: The findings suggest that CC
      morphology may be associated with the pathophysiology of bipolar disorder.

PMID- 17224094
TI  - The psychological costs of unsustainable housing commitments.
AB  - BACKGROUND: The extended recession and stagnant housing market in the 1990s
      following the boom of the late 1980s resulted in more than half a million housing
      repossessions. This study explores the impact of unsustainable housing
      commitments on psychological well-being. We test the hypotheses that housing
      payment problems and housing arrears have adverse impacts on heads of households'
      psychological well-being over and above those caused by financial hardship more
      generally. METHOD: Data came from the British Household Panel Survey 1991-2003
      and the samples for analysis consist of: (1) 5651 male head of households
      producing 26618 person-year observations, and (2) 2534 female head of households
      producing 9091 person-year observations. Summary statistics and multivariate,
      fixed effects regression models are used. Mental health was measured by the 12
      item General Health Questionnaire. RESULTS: For male heads of households housing
      payment problems and entering arrears have significant detrimental effects on
      mental well-being and for female heads of households longer-term housing payment
      problems and arrears have significant detrimental effects on mental well-being.
      The sizes of these effects are in addition to and larger in magnitude than those
      associated with financial hardship more generally. The net effects appear to be
      relatively stable over the time of the panel data. CONCLUSIONS: This study
      provides evidence that housing payment problems have independent psychological
      costs over and above those associated with general financial hardship. The
      magnitude of the effect is similar to that shown for marital breakdown and job
      loss.

PMID- 17224095
TI  - Using transcranial magnetic stimulation to investigate the cortical origins of
      motor overflow: a study in schizophrenia and healthy controls.
AB  - BACKGROUND: Previous research has confirmed the presence of increased motor
      overflow in schizophrenia. There are essentially two theories regarding the
      cortical origins of overflow. Recent research suggests that both may be correct,
      and that the cortical origin of overflow is highly dependent upon the population
      in which it presents. Motor overflow, due to an abnormally active ipsilateral
      corticospinal tract, may indicate a potentially severe brain abnormality arising
      in early development. In contrast, bilaterally active corticospinal tracts
      accounting for overflow probably represent a naturally occurring response during
      fatiguing contractions. METHOD: The cortical origins of motor overflow in 20
      participants with schizophrenia and 20 normal controls were investigated through
      the use of a number of transcranial magnetic stimulation (TMS) protocols.
      RESULTS: Each of the experimental protocols employed independently supported the
      contention that overflow was originating in the hemisphere contralateral to the
      involuntary movement. CONCLUSIONS: Results indicated that the origins of overflow
      in schizophrenia are the same as those seen in the normal control group, i.e.
      motor overflow seems to be due to the presence of bilaterally active
      corticospinal tracts. Potential explanations for greater motor overflow seen in
      schizophrenia are discussed.

PMID- 17224097
TI  - Participant distress in psychiatric research: a systematic review.
AB  - BACKGROUND: There has been ethical concern that participants in psychiatric
      research will become distressed and their mental state might worsen. METHOD: A
      systematic search was carried out for studies that examined distress following
      participation in research that involved the assessment of psychiatric state or
      associated risk factors. There were 46 relevant studies. RESULTS: A minority of
      participants become distressed immediately after participation, with distress
      more likely in studies of traumatic experiences. There is limited evidence on
      longer-term effects, but what there is suggests no adverse impact. Positive
      reactions to participation show little association with distress and these are
      more common than negative reactions. Very few studies of distress in research
      have used control groups to establish causal associations. However, what evidence
      there is suggests no causal role, including for research on suicidality.
      Researchers in this area have made a range of suggestions about ethical practice.
      CONCLUSIONS: A minority of participants in psychiatric research become
      distressed, but there is no evidence of longer-term harm. Nevertheless,
      researchers need to take account of ethical concerns in designing studies. Future
      research in the area needs to be carried out with stronger designs involving
      control groups.

PMID- 17224096
TI  - Enhanced emotion-induced amnesia in borderline personality disorder.
AB  - BACKGROUND: Current biological concepts of borderline personality disorder (BPD)
      emphasize the interference of emotional hyperarousal and cognitive functions. A
      prototypical example is episodic memory. Pre-clinical investigations of emotion
      episodic memory interactions have shown specific retrograde and anterograde
      episodic memory changes in response to emotional stimuli. These changes are
      amygdala dependent and vary as a function of emotional arousal and valence.
      METHOD: To determine whether there is amygdala hyper-responsiveness to emotional
      stimuli as the underlying pathological substrate of cognitive dysfunction in BPD,
      16 unmedicated female patients with BPD were tested on the behavioural indices of
      emotion-induced amnesia and hypermnesia established in 16 healthy controls.
      RESULTS: BPD patients displayed enhanced retrograde and anterograde amnesia in
      response to presentation of negative stimuli, while positive stimuli elicited no
      episodic memory-modulating effects. CONCLUSION: These findings suggest that an
      amygdala hyper-responsiveness to negative stimuli may serve as a crucial
      aetiological contributor to emotion-induced cognitive dysfunction in BPD.

PMID- 17224098
TI  - The heritability of cluster A personality disorders assessed by both personal
      interview and questionnaire.
AB  - BACKGROUND: Personality disorders (PDs) as assessed by questionnaires and
      personal interviews are heritable. However, we know neither how much
      unreliability of measurement impacts on heritability estimates nor whether the
      genetic and environmental risk factors assessed by these two methods are the
      same. We wish to know whether the same set of PD vulnerability factors are
      assessed by these two methods. METHOD: A total of 3334 young adult twin pairs
      from the Norwegian Institute of Public Health Twin Panel (NIPHTP) completed a
      questionnaire containing 91 PD items. One to 6 years later, 1386 of these pairs
      were interviewed with the Structured Interview for DSM-IV Personality (SIDP-IV).
      Self-report items predicting interview results were selected by regression.
      Measurement models were fitted using Mx. RESULTS: In the best-fit models, the
      latent liabilities to paranoid personality disorder (PPD), schizoid personality
      disorder (SPD) and schizotypal personality disorder (STPD) were all highly
      heritable with no evidence of shared environmental effects. For PPD and STPD,
      only unique environmental effects were specific to the interview measure whereas
      both environmental and genetic effects were found to be specific to the
      questionnaire assessment. For SPD, the best-fit model contained genetic and
      environmental effects specific to both forms of assessment. CONCLUSIONS: The
      latent liabilities to the cluster A PDs are highly heritable but are assessed by
      current methods with only moderate reliability. The personal interviews assessed
      the genetic risk for the latent trait with excellent specificity for PPD and STPD
      and good specificity for SPD. However, for all three PDs, the questionnaires were
      less specific, also indexing an independent set of genetic risk factors.

PMID- 17224099
TI  - [To invest in the health of our children is to invest in the future of Mexico].

PMID- 17224100
TI  - [Transient evoked otoacoustic emissions (TEOAEs) in patients with acute middle
      ear pathology].
AB  - BACKGROUND: A transverse study was carried out with the objective of describing
      the alterations found in the reproducibility response and extent of the transient
      evoked otoacustic emissions (TEOAEs) in patients with acute middle ear pathology
      with standard audiometry of normal hearing or minimal auditory deficit in the
      preschool population. METHODS: Audiometric tests were performed such as tonal
      audiometry, visual reinforcement audiometry or by guided training, depending on
      the age and cooperation of the subject, conventional tympanometric and
      accomplishment on TEOAE. RESULTS: Obtained data show an adequate reproducibility
      response total in 17.2% of the cases and extent of response preserved in 19.7% of
      the cases. This demonstrates that the extent and the reproducibility are affected
      in an important way in acute middle ear pathology. CONCLUSIONS: TEOAEs are a
      diagnostic method in patients with acute middle ear pathology and are useful in
      patients difficult to examine.

PMID- 17224101
TI  - [Coronary artery bypass graft surgery in patients with acute coronary syndrome.
      Analysis of results].
AB  - BACKGROUND: The objective of this work was to determine the main risk factors
      that influence prognosis, results, morbidity and mortality rates and causes in
      patients with acute coronary syndrome requiring surgical myocardial
      revascularization. METHODS: This was a retrospective study including patients in
      our hospital with acute coronary syndrome requiring coronary artery bypass-graft
      surgery between January 2000 and December 2003. The following were identified and
      compared with international values: demographic factors, indications for surgery,
      intercurrent pathologies, results of the procedures, morbidity and mortality
      rates and causes. RESULTS: There were 73 males and 23 females with an age range
      of 46 to 88 years old. The main cause of surgery was unstable angina (42.7%). In
      two patients, surgery was indicated for percutaneous coronary angioplasty failure
      and in 28 patients due to mechanical complications of acute myocardial
      infarction. The procedure was urgent in 90.6%. The majority of patients were in
      Killip-Kimball or Forrester class I or II. Risk factors detected were left
      ventricular failure, mechanical complications, emergency surgery, diabetes and
      respiratory or renal failure. Perioperative mortality was 14.5% and morbidity was
      41.6%, both compared with risk classification scales and were lower than expected
      according to Parsonet and Tuman evaluations. CONCLUSIONS: With a major number of
      risk factors and the high-risk associated with surgery, in our center surgical
      treatment for acute coronary syndromes showed favorable results.

PMID- 17224102
TI  - [Experience with Clotteau-Premont's technique in abdominal wall hernias.
      Preliminary report].
AB  - BACKGROUND: Incisional hernias account for at least a third of abdominal wall
      hernias. There are different techniques of repair that include the use of
      prosthetic materials, which has lowered the hernia recurrence rate. Nonetheless,
      its use in case of rejection or infection requires other techniques with local
      tissue. The use of prosthetic material in a contaminated environment is
      contraindicated because the risk of infection and recurrence rate is unacceptably
      high. METHODS: In order to compare two repair techniques for abdominal wall
      hernias in terms of complications and recurrence to be used as an alternative for
      hernia repair in patients with abdominal wall hernias, we conducted, between
      January 2000 and January 2004, an observational, longitudinal, retrospective, non
      randomized matched control case study in patients with abdominal wall hernia. A
      total of 30 patients were studied and were divided into two groups of 15 patients
      each. Subjects were matched for sex, age and hernia type (group A, mesh treated
      and group B, Clotteau-Premont treated) who had at least a 5-month postoperative
      follow-up. Complication and recurrence rate was assessed and compared. RESULTS:
      There were no differences between the two groups in complications or recurrence
      (p <0.05). The average follow-up time was 18.9 +/- 8 months for group A and 15 +/
      7.9 months for group B. CONCLUSIONS: Clotteau-Premont's technique is a safe and
      feasible alternative procedure with indications in selected patients.

PMID- 17224104
TI  - [Radiographic measurements of the wrist in healthy Mexicans].
AB  - BACKGROUND: We undertook this study to determine normal radiographic measurements
      of the wrist in healthy Mexican persons. METHODS: We performed 112 roentgenograms
      of healthy wrists, 56 left wrists and 56 right wrists, in normal adults with
      Mexican parents and grandparents who were born in Mexico. We made two
      projections: frontal and lateral views of the wrist sing a standard technique.
      Not included in the study were subjects with a history of wrist trauma, fractures
      or deformities. The measurement was done by two observers blinded to the study.
      We measured ulnar lengths, radial angulation, volar shift, volar tilt and dorsal
      shift. RESULTS: We found a mean in radial angulation of 36.5 degrees +/- 4.62
      degrees , dorsal shift 22.84 mm +/- 3.23 mm, ulnar lengths -1.13 mm +/- 2.61 mm,
      radial tilt 17.98 degrees +/- 2.25 degrees and volar shift of 19.3 mm +/- 9.3 mm.
      No significant difference between the left and right wrist or in the dominant
      wrist was found. We found a correlation between radial angulation, radial tilt
      and dorsal shift, and the height with the dorsal shift. There were significant
      differences among men and women in the radial angulation, dorsal shift and volar
      shift. CONCLUSIONS: There were differences in the radial angulation and radial
      tilt with respect to values reported in the U.S. and Sweden. In the ulnar lengths
      there were difference with respect to the values reported in Taiwan and Japan.
      Information regarding normal values in wrist measurements could be used as the
      normal reference value for the evaluation of surgical management and follow-up of
      the wrist.

PMID- 17224103
TI  - [Morbi-mortality of Hartmann's reversal procedure].
AB  - BACKGROUND: Hartmann's operation is an alternative for emergency colorectal
      surgeries, but its reversal may be difficult and prone to complications. A longer
      interval for its reversal has been recommended to decrease complications.
      METHODS: In order to determine rates of morbi-mortality and to ascertain the
      association between the time interval for its reversal and presence of
      complications, we undertook a retrospective analysis of 48 patients with a mean
      age of 57 +/- 16 years. Nineteen patients (40%) were >65 years, and 21 (44%) had
      one or more underlying chronic disease. Perioperative factors associated with
      morbi-mortality were determined by means of the Mann-Whitney U test and Fisher
      exact test. RESULTS: Acute diverticulitis was the most frequent indication (42%).
      Mean interval between Hartmann's operation and its reversal was 8 months (range:
      1 to 46 months). Mean duration of the reversal operation was 267 min (range: 120
      to 540 min). There were complications in 29 patients (60%) including anastomotic
      leaks in 6 (12%) and operative deaths in 4 (8%). A shorter interval between
      Hartmann's operation and its reversal was not associated with more complications
      or longer surgical time. CONCLUSIONS: Hartmann's reversal operation has high
      rates of morbidity and mortality that are not influenced by the time interval
      from the original operation.

PMID- 17224105
TI  - [Rating scale for osteoarthritis knee assessment].
AB  - BACKGROUND: We undertook this study to develop a grading scale to assess knee
      osteoarthritis using the Bristol Score. METHODS: Between August and November
      2004, a clinimetrical, prospective, group-controlled, observational, cross
      sectional and analytical study was done. The study sample was comprised of 55
      patients, 35 years old and over, with clinical-radiographic diagnosis of knee
      osteoarthritis following the American Academy of Rheumatology criteria. The
      Bristol Score was used in 25 patients by two standardized orthopedic surgeons.
      Sensitivity, consistency and validity of the Bristol Score were determined. The
      new grading scale to assess osteoarthritis Magdalena de las Salinas H-1(MSH1) was
      used in 30 patients. Sensitivity, consistency and validity of the MSH1 were also
      determined. Both indexes were compared in these terms. An osteoarthritis
      radiographic score was developed to assess the validity of the MSH1. RESULTS:
      Inter-observer intraclass correlation coefficient (ICC) for the Bristol Score in
      its categories was total 0.62, function 0.84, pain 0.40 and movement 0.89. Inter
      observer ICC for MSH1 in its categories was total 0.91, function 0.92, pain 0.79
      and movement 0.86 (p <0.0001). Inter-observer weighed kappa of the Bristol Score
      was 0.51 (p = 0.002), with 80% agreement. The weighed kappa for the MSH1 was 0.81
      (p <0.0001) with 90% agreement. Correlation between the Bristol Score and the
      osteoarthritis radiographic score was -0.29 (p = 0.049). Correlation between the
      MSH1 and the radiographic score of osteoarthritis was -0.62 (p <0.01).
      CONCLUSIONS: MSH1 achieved better validity than the Bristol Score and can be
      considered a reliable instrument to assess knee osteoarthritis.

PMID- 17224106
TI  - [Complications in complex fractures of the tibial plateau and associated
      factors].
AB  - BACKGROUND: We undertook this study to identify factors associated with surgical
      complications of complex fractures of the tibial plateau. METHODS: We designed a
      case-control study with 56 patients with a diagnosis of complex fracture in the
      tibial plateau (IV-VI Schatzker) and with 12.9 +/- 3.2 (8-18) months of follow
      up. Risk factor exposure was defined as having one or more of the following
      characteristics: age >60 years; co-morbidity (diabetes mellitus, systemic
      arterial hypertension); time of "Kidde" (>60, >90, >120 min) and fracture type
      IV, V or VI. A case was considered with one or more complications. RESULTS: Mean
      age was 50.1 +/- 15.7 (17-87) years old; 35 patients (62.5%) were males.
      Homogeneity between groups was shown for age, sex, side effects, type of fracture
      and time of follow-up; 41.1% of patients had pathological history. All surgeries
      used pneumatic compression (Kidde) for 91 +/- 27.2 (40-175) min. The implants
      used were plate plus cancellous screws (53.6%), external fixators plus cancellous
      screws (35.7%), double plate and intramedullary nail. Complications appeared in
      37.5% of all patients. Complications reported were superficial infection (16.1%),
      residual angular deformities (10.7%, varum [7.1%]), peroneal nerve injury (5.4%),
      non-union (3.5%) and deep venous thrombosis (1.8%); 22.2% of all patients
      presented more than one complication. CONCLUSIONS: Statistically significant risk
      factors were age >60 years and pneumatic compression >120 min. Patients with one
      of these characteristics had a three-times risk of complications. No association
      was demonstrated between type of fracture, surgical treatment, time between
      injury and the surgery, with development of complications.

PMID- 17224107
TI  - [Emergencies and urgent medical-surgical conditions attended at a comprehensive
      cancer center].
AB  - The global incidence of emergencies and urgent medical?surgical conditions in
      cancer patients has not been well described. The aim of the study was to identify
      the main symptoms and diagnoses in patients seen for consultation at the Urgent
      Care Service in a Mexican Comprehensive Cancer Center. This was a retrospective
      observational study. The information was obtained from the Continuous Admission
      Service daily consultation records at the Oncology Hospital, National Medical
      Center "21st Century," Institute of Social Security, Mexico City. During a 6
      month period, 4937 patients were seen for consultation. True oncologic
      emergencies were 3.7%, urgencies 52.5% and non-urgent were 43.7%. Most common
      symptoms for emergency and urgency patient consultations were severe pain (69.5%)
      and dehydration with electrolyte imbalance (11.4%). Prevalent symptoms were
      associated with the primary tumor or metastatic dissemination (89% cases). The
      most frequent baseline diseases were breast, colorectal, cervical, lung and
      stomach carcinomas. Defined oncologic emergencies in this series were septic
      shock and severe neutropenia (20%), hypovolemic shock due to severe bleeding
      (16.5%), and severe dyspnea due to pneumonia or pleural efusion (12%). Data
      evaluating the use of analgesic drug therapy for cancer pain alone indicate that
      80% of patients report adequate analgesia. Analgesia failures were associated
      with an insufficient prescription or with inadequate consumption of opioid
      analgesics. The Urgent Care Center at a Comprehensive Cancer Center offers the
      best opportunity for diagnosis and treatment of emergencies and urgent care
      conditions in cancer patients.

PMID- 17224108
TI  - [Torsion of the vermiform appendix associated with intussusception].
AB  - BACKGROUND: Vermiform appendix torsion is a rare condition, with only 25 cases
      recorded in the international literature. Our patient is the first case
      associated with intussusception. CASE REPORT: A 2-month-old female infant
      suddenly developed severe abdominal pain due to ileoceal intussusception. During
      surgical exploration, a tight intussusception was reduced. Three days later, a
      new laparotomy was required and we found torsion and perforation of the vermiform
      appendix. The patient underwent appendectomy, but there was dehiscence of the
      appendiceal stump and cecal perforation requiring a new surgical exploration. The
      patient had an uneventful recovery.

PMID- 17224109
TI  - [Intergluteal angiokeratoma circumscriptum. Report of one case].
AB  - BACKGROUND: The term angiokeratoma is applied to several diseases with cutaneous
      vascular lesions. CLINICAL CASE: A 26-year-old male presented with an
      intergluteal tumor from childhood until the present time, which was treated on
      several occasions without results. The patient presented to the hospital
      complaining of a painful and bleeding intergluteal tumor. DISCUSSION: Five types
      of angiokeratomas have been described (angiokeratoma corporis diffusum,
      angiokeratoma of Mibelli, angiokeratoma of Fordyce, solitary angiokeratoma and
      angiokeratoma corporal circumscriptum). This patient was identified with an
      angiokeratoma circumscriptum by pathological and physical characteristics of the
      tumor. Differential diagnosis is with verrucous hemangioma and the Fabry disease
      type II (angiokeratoma corporis diffusum). CONCLUSION: Pathogenesis is unknown
      and surgery is the recommended treatment.

PMID- 17224110
TI  - [Aneurysmal bone cyst of the spine. Case report].
AB  - The aneurysmal bone cyst (ABC) is a fast-growing tumor of undefined neoplastic
      nature. It is occasionally an aggressive benign lesion whose treatment of choice
      is a complete resection, even though the risk of profuse transoperative bleeding
      exists. We present a female patient with thoracic spine deformity, with
      progressive paresthesias and muscle weakness of lower extremities that evolved to
      paralysis of both lower extremities and sphincter incontinence. Based on
      radiographic films, lytic lesions were identified at T7 to T9 vertebrae as well
      as medullary space invasion. In electrophysiologic tests, a complete
      somatosensorial pathway block was reported. Prior to resection of the neoplastic
      lesion and thoracolumbar stabilization, an incisional biopsy was performed. There
      was no postoperative medullary functional improvement. Morphological findings
      corresponded to an aneurysmal bone cyst at T8. This lesion is mainly located in
      the long bones and less frequently of the spine, where instability and medullary
      compression may occur. It is possible to confuse this neoplasia with other
      lesions. Hence, definite diagnosis with biopsy is necessary for determining an
      adequate therapeutic plan to eradicate recurrence risk or associated neurologic
      sequelae, as well as to gain proper stability at the involved vertebral segments.

PMID- 17224111
TI  - [Practice guidelines for cancer pain management. Task Force for Cancer Pain
      Management].
AB  - Cancer pain is a frequent medical problem in our society. This syndrome affects
      from 80 to 90% of cancer patients and can be solved with relatively simple
      measures in 90% of the cases. Approximately 40% of cancer patients reported to be
      unsatisfied with the physician or nurse about their pain management. For these
      reasons, we gathered a task force in order to generate practice guidelines based
      on medical evidence and on the opinion of experts in this area. These guidelines
      were generated by a task force of 31 physicians who were leaders in this field
      and based on 599 papers selected by a previous literature search. This group
      evaluated the results of this search in three work sessions, during which a level
      of evidence was assigned to each recommendation.

PMID- 17224112
TI  - [Foundation and organization of the University of Bologna from the XII century to
      the Renaissance].
AB  - The University of Bologna was founded in 1150 and was the first European
      University to establish this educational trend. The combination of structured
      teaching and student associations marked the origin of the studium generale. The
      presence of teaching legists encouraged teachers in others fields to come to
      Bologna. Ars dictaminis, grammar, logic, philosophy, mathematics and especially
      medicine were taught there by the middle of the thirteenth century. The
      university offered advanced instruction in law, medicine, and theology and had a
      minimum of six to eight professors teaching civil law, canonical law, medicine,
      logic, natural philosophy and usually rhetoric. Many professors bearing local
      names were learned scholars and commanding figures in medicine and surgery.
      Taddeo Alderotti (1210-1295) began to teach medicine in Bologna in about 1260. He
      soon raised medicine to a prestigious position in the university. The
      geographical distribution demonstrates the international distribution of the
      student body: 73% were Italians and 26% non-Italians. The decision of the
      legislature of Bologna to take control of the university from the students by
      paying professors was probably the most important decision in the history of
      Italian universities. Examination of the distribution of professors offers a
      detailed picture of the faculty. In 1370 the university had 11 professors of
      civil law, 7 professors of canonical law, 3 professors of medical theory, 2
      professors of medical practice (specifically of diagnosis and treatment), and 1
      professor of surgery. After growing steadily, the numbers of teachers stabilized
      at 85 to 110 until the year 1530.

PMID- 17224114
TI  - [Re: Esophageal perforation. Cir Ciruj 2005;73:431-6].

PMID- 17224115
TI  - Thin wetting films from aqueous solutions of surfactants and phospholipid
      dispersions.
AB  - The microscopic thin wetting film method was used to study the stability of
      wetting films from aqueous solution of surfactants and phospholipid dispersions
      on a solid surface. In the case of tetradecyltrimethylammonium bromide (C(14)TAB)
      films the experimental data for the receding contact angle, film lifetime,
      surface potential at the vapor/solution and solution/silica interface were used
      to analyze the stability of the studied films. It is shown that with increasing
      C(14)TAB concentration charge reversal occurs at both (vapor/solution and
      solution/silica) interfaces, which affects the thin-film stability. The
      spontaneous rupture of the thin aqueous film was interpreted in terms of the
      earlier proposed heterocoagulation mechanism. The presence of the mixed
      cationic/anionic surfactants was found to lower contact angles and suppresses the
      thin aqueous film rupture, thus inducing longer film lifetime, as compared to the
      pure amine system. In the case of mixed surfactants hetero-coagulation could
      arise through the formation of ionic surfactant complexes. The influence of the
      melting phase-transition temperature T(c) of the dimyristoylphosphatiddylcholine
      (DMPC) on the stability of thin films from dispersions of DMPC small unilamellar
      vesicles on a silica surface was studied by measuring the film lifetime and the
      TPC expansion rate. The stability of thin wetting films formed from dispersions
      of DMPC small unilamellar vesicles was investigated by the microinterferometric
      method. The formation of wetting films from diluted dispersions of DMPC
      multilamellar vesicles was studied in the temperature range 25-32 degrees C. The
      stability of thin film of lipid vesicles was explained on the basis of
      hydrophobic interactions. The results obtained show that the stability of wetting
      films from aqueous solutions of single cationic and mixed cationic-anionic
      surfactants has electrostatic origin, whereas the stability of the phospholipid
      film is due to hydrophobic interaction.

PMID- 17224117
TI  - Identification of scanning slit-beam topographic parameters important in
      distinguishing normal from keratoconic corneal morphologic features.
AB  - PURPOSE: To identify morphologic parameters obtained using scanning slit-beam
      topography that help distinguish normal from keratoconic corneal morphologic
      features. DESIGN: Observational, retrospective, cross-sectional study. METHODS:
      This retrospective review examined 207 normal eyes of patients undergoing an
      initial consultation for primary refractive surgery and 42 eyes with clinical
      keratoconus (KCN). The following parameters were examined and compared between
      the two groups: astigmatism, central corneal power, irregularity indices at 3 mm
      (II3) and 5 mm (II5), maximal posterior elevation (MPE) magnitude and location,
      thinnest optical pachymetry (TOP) magnitude and location, anterior elevation best
      fit sphere (ABFS), posterior elevation best-fit sphere (PBFS), the ratio of ABFS
      to PBFS, the difference between average inferior and average superior K values at
      3 mm and 5 mm in both keratometric (I-S K3 and I-S K5) and tangential (I-S T3 and
      I-S T5) topographic maps, and skewed radial axis at 3 mm (SRAX3) and 5 mm (SRAX5)
      of the keratometric topography map. RESULTS: The II3, II5, MPE magnitude, TOP
      magnitude, ABFS, PBFS, ABFS-to-PBFS ratio, I-S K at both 3 mm and 5 mm, I-S T at
      both 3 and 5 mm, and SRAX at 3 mm and 5 mm values were significantly different
      among the two groups (P < .001). The least-correlated parameters were SRAX3, TOP
      magnitude, and II3 in the KCN group and I-S K3, amount of astigmatism and MPE
      magnitude in the normal group. CONCLUSIONS: Parameters obtained using scanning
      slit-beam topography may allow improved differentiation of keratoconic from
      normal corneal shapes, especially when the poorly correlated intragroup
      parameters are used.

PMID- 17224116
TI  - Risk factors for ocular complications and poor visual acuity at presentation
      among patients with uveitis associated with juvenile idiopathic arthritis.
AB  - PURPOSE: To describe the frequencies of and risk factors for ocular complications
      and poor visual acuity at presentation in a cohort of patients with juvenile
      idiopathic arthritis (JIA)-associated uveitis. DESIGN: Cross-sectional study.
      METHODS: setting: Single-center, academic practice. study population: Seventy
      five patients with JIA-associated uveitis were evaluated between July 1984 and
      August 2005. observation procedures: Data on patients diagnosed with JIA
      associated uveitis were entered retrospectively into a database and analyzed.
      outcome measures: Visual acuity of 20/50 or worse or 20/200 or worse, and
      presence of ocular complications (including cataract, posterior synechiae, band
      keratopathy, elevated intraocular pressure, hypotony, macular edema, and
      epiretinal membrane) at presentation. RESULTS: At presentation, ocular
      complications were seen in 67% of eyes affected by JIA-associated uveitis.
      Presence of > or =1+ anterior chamber flare, a positive antinuclear antibody
      (ANA), and a shorter duration between the diagnosis of arthritis and uveitis were
      significantly associated with the presence of ocular complication. The
      frequencies of 20/50 or worse and of 20/200 or worse visual acuities at
      presentation in affected eyes were 36% and 24%, respectively. The presence of >
      or =1+ anterior chamber flare and a history of intraocular surgery before
      presentation were significantly associated with 20/50 or worse and 20/200 or
      worse vision. Presence of posterior synechiae also was associated with 20/200 or
      worse vision at presentation. The main causes of poor vision at presentation for
      affected eyes and better-seeing eyes were cataract, band keratopathy within the
      visual axis, and glaucoma. CONCLUSIONS: Ocular complications and poor vision at
      presentation were common in our patients with JIA-related uveitis.

PMID- 17224118
TI  - Evaluation of keratoconus in Asians: role of Orbscan II and Tomey TMS-2 corneal
      topography.
AB  - PURPOSE: To evaluate the corneal topographic patterns of Asian patients with
      keratoconus (KC). DESIGN: Prospective observational case-control study. METHODS: 
      SETTING: Institutional. STUDY POPULATION: A total of 116 patients (both eyes
      included) with KC were recruited. The control group consisted of 70 laser in-situ
      keratomileusis (LASIK) candidates with myopia. Patients with previous ocular
      surgery and trauma were excluded. OBSERVATION PROCEDURE: Corneal topography was
      performed using the Tomey KC screening system (Topographic Modeling System,
      software version 2.4.2J, Tomey Corp, Nagoya, Japan) and Orbscan II corneal
      topography system (Bausch & Lomb Surgical, Orbtek Inc, Salt Lake City, Utah,
      USA). MAIN OUTCOME MEASURES: Videokeratographic variables were analyzed and the
      eyes were grouped into KC, KC suspect, and control groups. RESULTS: The corneal
      topographic patterns of 196 eyes were analyzed. The topographic patterns
      displayed by Tomey (TMS-2N) and Orbscan II were similar. The majority of eyes
      with KC (71.2%) and KC suspect (70%) had asymmetric bowtie patterns. Thirteen
      indices of TMS-2N were analyzed and the means of the indices were found to be
      significantly higher in eyes in the KC group than the KC suspect group (P <
      .001). Fourteen indices of Orbscan II were analyzed. Eyes in the KC suspect group
      had higher mean posterior elevation (46 +/- 17 microm), 3 mm irregularity (2.44
      +/- 1.36 diopters [D]), 5 mm irregularity (2.61 +/- 1.19 D) and had thinner
      corneas (mean 504.4 +/- 40.4 microm) than normal eyes (26 +/- 8 microm, 1.05 +/-
      0.37 D, 1.38 +/- 0.39 D, and 554.0 +/- 25.0 microm, respectively). CONCLUSION:
      Corneal topography pattern recognition combined with quantitative diagnostic
      indices is useful for the screening and classification of KC with the Orbscan II
      being more sensitive in screening for KC than TMS-2N.

PMID- 17224119
TI  - Efficacy of different intraocular lens materials and optic edge designs in
      preventing posterior capsular opacification: a meta-analysis.
AB  - PURPOSE: To evaluate the efficacy of different intraocular lens (IOL) materials
      and optic edge designs in preventing posterior capsular opacification (PCO).
      DESIGN: Systematic review and meta-analysis. METHODS: Pertinent studies were
      selected through an electronic search of the Cochrane Library, MEDLINE, and
      Embase. The randomized controlled trials meeting the predefined criteria were
      reviewed systematically by meta-analysis. The treatment effects were measured as
      risk difference, and the pooled estimates were computed according to a random
      effect model. RESULTS: In total, 23 randomized controlled trials were included in
      the present meta-analysis. The pooled risk differences of Nd:YAG laser
      capsulotomy rates were -24% (95% confidence interval [CI], -29% to -20%)
      comparing acrylic with polymethylmethacrylate (PMMA) lenses; -9% (95% CI, -17% to
      -1%) comparing silicone with PMMA lenses; 14% (95% CI, -8% to 36%) comparing
      hydrogel with PMMA lenses; 4% (95% CI, -2% to 10%) comparing silicone with
      acrylic lenses; 19% (95% CI, 8% to 30%) comparing hydrogel with acrylic lenses;
      and 28% (95% CI, 10% to 46%) comparing hydrogel with silicone lenses. The pooled
      risk differences of PCO rates were -39% (95% CI, -47% to -31%) comparing acrylic
      with PMMA lenses; -14% (95% CI, -29% to 0%) comparing silicone with acrylic
      lenses; 56% (95% CI, 36% to 75%) comparing hydrogel with acrylic lenses; and 48%
      (95% CI, 31% to 64%) comparing hydrogel with silicone lenses. When comparing
      sharp with rounded-edge designs, pooled risk differences of capsulotomy rates
      were -47% (95% CI, -77% to -17%) in PMMA lenses, -22% (95% CI, -47% to 2%) in
      acrylic lenses, and -9% (95% CI, -17% to 0%) in silicone lenses; pooled risk
      differences of PCO rates were -28% (95% CI, -50% to -7%) in acrylic lenses and 
      37% (95% CI, -46% to -27%) in silicone lenses. CONCLUSIONS: The rates of PCO and
      Nd:YAG laser capsulotomy may be influenced by different IOL biomaterials and
      optic edge designs. The lenses made by acrylic and silicone and those with sharp
      optic edges are superior in lowering the rates of PCO and laser capsulotomy.

PMID- 17224120
TI  - Detection of abnormal visual cortex in children with amblyopia by voxel-based
      morphometry.
AB  - PURPOSE: To detect the abnormalities of gray matter in children with amblyopia by
      voxel-based morphometry (VBM). DESIGN: Prospective, nonrandomized clinical trial.
      METHODS: Thirteen children with amblyopia and 14 normally sighted children
      underwent magnetic resonance (MR) examination. The two groups were age-matched
      with a mean age of 5.8 years. In the amblyopia group, five children had
      strabismus amblyopia, and eight had anisometropic amblyopia. We analyzed the
      original 3-dimensional T1 brain images using the VBM module within the widely
      used analysis software package SPM2 (Welcome Department of Cognitive Neurology,
      London, United Kingdom). After normalization, segmentation, and smoothing of the
      images, comparison between amblyopic and control groups was derived for the gray
      matter of the entire brain using parametric statistics. RESULTS: The results of
      VBM analysis indicated that the amblyopic group had decreased gray matter density
      in the middle frontal gyrus, parahippocampal gyrus, fusiform gyrus, inferior
      temporal gyrus of the left hemisphere, and the bilateral calcarine cortices. The
      radii of these regions ranged from 12 to 36 voxels. These abnormalities were
      consistent with morphologic changes in brain regions related to visual function.
      CONCLUSIONS: Using MR and VBM analysis, we detected morphologic changes in the
      visual cortex of children with amblyopia, which may indicate developmental
      abnormalities of visual cortex during the critical growth period.

PMID- 17224121
TI  - Nuclear receptor 4A2 and C/EBPbeta regulate the parathyroid hormone-mediated
      transcriptional regulation of the 25-hydroxyvitamin D3-1alpha-hydroxylase.
AB  - 1Alpha-hydroxylase is the enzyme responsible for the production of the active
      form of vitamin D, 1,25-dihydroxyvitamin D3. 1Alpha-hydroxylase, found largely in
      the kidney, is known to be up-regulated by parathyroid hormone (PTH), however the
      mechanism of action of PTH and any required transcription factors have not been
      clearly identified. During gene array analysis we observed that NR4A2, a nuclear
      orphan receptor, is markedly up-regulated in a porcine kidney cell line (AOK-B50)
      following PTH stimulation. NR4A2 over-expression increases the endogenous
      induction of 1alpha-hydroxylase mRNA in the absence of PTH, however optimal
      stimulation is achieved when both NR4A2 and PTH are present. An unconventional
      site of action of NR4A2 was localized to a fragment comprising the sequence from 
      35/+22 of the 1alpha-hydroxylase promoter at a C/EBP consensus site. Study of the
      involvement of C/EBPbeta in the 1alpha-hydroxylase regulation revealed that the
      transcriptional enhancement by NR4A2 on the 1alpha-hydroxylase promoter is
      inhibited by C/EBPbeta. In addition, C/EBPbeta over-expression decreases the
      endogenous levels of both NR4A2 and 1alpha-hydroxylase mRNA.

PMID- 17224123
TI  - RGD-peptide presents anti-adhesive effect, but not direct pro-apoptotic effect on
      endothelial progenitor cells.
AB  - Circulating endothelial progenitor cells (EPCs) contribute to neovascularization
      in tumor or ischemic tissues by multi-step events, including adhesion, migration,
      chemoattraction, and differentiation to endothelial cells. Anti-angiogenic RGD
      peptides have been shown to directly induce apoptosis in human umbilical vein
      endothelial cells (HUVECs) and T cells. Here, we examined the effects of RGD
      peptides on EPCs in terms of adhesive differentiation and apoptosis. When
      mononuclear cells (MNCs) isolated from human cord blood were cultured on
      fibronectin-coated plates for 7 days, RGD-peptide treatment decreased dose
      dependently the number of adherent cells double positive for DiI-ac-LDL uptake
      and UEA-1 binding. The cells treated with RGD peptide were also stained less
      strongly by vWF or KDR antibody by immunofluorescence staining. Immobilization of
      the RGD-peptide promoted cell adhesion, but resulted in a deficiency in the
      development of ability of ac-LDL uptake and UEA-1 binding, showing an
      antagonistic effect. Accordingly, ex vivo-cultivated EPCs expressed integrin
      alpha5, alphav, beta1, beta3, and beta5, and antibodies to integrins alpha5,
      alphav, and beta1 decreased the number of adherent cells. However, viability of
      total MNCs containing early EPCs was not affected by RGD-peptide. In addition,
      neither an increase in apoptotic cell death nor a direct activation of caspase-3
      by RGD-peptide was detected in ex vivo-cultivated EPCs, unlike in HUVECs.
      Interestingly, RGD-peptide rather enhanced Bcl-2 expression in ex vivo-cultivated
      EPCs and the EPCs themselves with a high Bcl-2/Bax ratio are comparatively
      resistant to apoptosis. Therefore, these results suggest that RGD-peptides may
      inhibit EPC differentiation by anti-adhesive effect, but not by a direct pro
      apoptotic effect.

PMID- 17224122
TI  - 1,2-GG intrastrand cross-link of antitumor dinuclear bifunctional platinum
      compound with spermidine linker inhibits DNA polymerization more effectively than
      the cross-link of conventional cisplatin.
AB  - In order to learn more about the molecular basis for the inhibition of DNA
      replication produced by antitumor platinum drugs, we investigated DNA
      polymerization using DNA templates site-specifically modified with the 1,2-GG
      intrastrand cross-link of dinuclear bifunctional [{trans-PtCl(NH(3))(2)}(2){l
      spermidine-N1,N8}](3+)(BBR3571) or conventional mononuclear cisplatin. These
      cross-links which have the same nature, but differ in the size and character of
      the conformational alteration induced in double-helical DNA, were analyzed for
      bypass ability with reverse transcriptase of human immunodeficiency virus type 1
      and Klenow fragment of DNA polymerase I deficient in exonuclease activity. We
      found that the 1,2-GG intrastrand CL of BBR3571 inhibited DNA translesion
      synthesis markedly more than the same adduct of cisplatin. This result was
      explained by a larger size of the cross-link of BBR3571 and by a flexibility
      induced in DNA by this cross-link which can make the productive binding of this
      adduct at the polymerase site more difficult.

PMID- 17224124
TI  - Generation of a homology model for the human cytochrome P450, CYP24A1, and the
      testing of putative substrate binding residues by site-directed mutagenesis and
      enzyme activity studies.
AB  - A systematic analysis of conserved H-bonding patterns and tertiary structural
      motifs from 13 crystal structures was used to create a homology model for the
      human multicatalytic cytochrome P450, CYP24A1, involved in catabolism of
      1alpha,25-dihydroxyvitamin D3. The substrate was docked in the active site and
      used to identify potential substrate contact residues in the B' helix, B'/C loop,
      F-helix and the beta-5 hairpin. Seven CYP24A1 mutants were created and studied by
      mammalian cell transfection and CYP24A1 activity assay. Mutants showed reduced
      metabolic rates and altered metabolite patterns compared to wild-type. We
      conclude that: Ile-131 positions substrate via A-ring and cis-triene contacts;
      Trp-134 and Gly-499 are determinants of substrate access; Leu-148 contacts the
      substrate side-chain; Met-246 is important in mediating regioselectivity. Our
      findings validate the new model of CYP24A1, which can now be used to predict
      structural modifications for rational vitamin D drug design.

PMID- 17224125
TI  - Duodenal calcium absorption in dexamethasone-treated mice: functional and
      molecular aspects.
AB  - Reduced intestinal calcium absorption may be part of the pathogenesis of
      glucocorticoid-induced osteoporosis. 1,25(OH)2D3 is the major regulator of the
      expression of the active duodenal calcium absorption genes: TRPV6 (influx),
      calbindin-D9K (intracellular transfer) and PMCA1b (extrusion). We investigated
      the influence of dexamethasone (5 days: 2 mg/kg bw) on calcium absorption in vivo
      and on the expression of intestinal and renal calcium transporters in calcium
      deprived mice. Total and free 1,25(OH)2D3-concentrations were halved, in line
      with decreased 25(OH)D3-1-alpha-hydroxylase and increased 24-hydroxylase
      expression. Nevertheless, no difference in duodenal or renal calcium transporter
      expression pattern could be detected between vehicle and dexamethasone-treated
      mice. Accordingly, dexamethasone did not affect in vivo calcium absorption. By
      contrast, increased calcemia and collagen C-terminal telopeptide levels reflected
      increased bone resorption. Decreased osteocalcin levels suggested impaired bone
      formation. Hence, short-term glucocorticoid excess in young animals affected bone
      metabolism without detectable changes in intestinal or renal calcium handling.

PMID- 17224126
TI  - Calbindin D9k is not required for 1,25-dihydroxyvitamin D3-mediated Ca2+
      absorption in small intestine.
AB  - The exact role of calbindin D9k in vitamin D-mediated calcium absorption has been
      debated but remains unsettled. In 129/OlaHsd mice, calbindin D9k was found
      highest in duodenum (36-50%) and kidney (24-34%) followed by stomach, lung and
      uterus. Age does not affect the relative distribution of calbindin D9k but it
      does decline with age in duodenum of both male and female 129/Ola mice. Recently,
      we produced a null calbindin D9k mutant 129/OlaHsd mouse; this mouse proved to be
      indistinguishable from the wild-type in phenotype and in a serum calcium level
      regardless of age or gender. We have now examined directly whether the mutant
      mouse can absorb calcium from the intestine in response to the active form of
      vitamin D. The calbindin D9k null mutant mouse is fully able to absorb calcium
      from the intestine in response to 1,25-dihydroxyvitamin D3. It is, therefore,
      clear that calbindin D9k is not required for vitamin D-induced intestinal calcium
      absorption.

PMID- 17224127
TI  - Catalytic mechanism of hydride transfer between NADP+/H and ferredoxin-NADP+
      reductase from Anabaena PCC 7119.
AB  - The mechanism of hydride transfer between Anabaena FNR and NADP+/H was analysed
      using for the first time stopped-flow photodiode array detection and global
      analysis deconvolution. The results indicated that the initial spectral changes,
      occurring within the instrumental dead time upon reaction of FNR with NADP+/H,
      included not only the initial interaction and complex formation, but also the
      first subsequent steps of the sequential reactions that involve hydride transfer.
      Two different charge-transfer complexes formed prior and upon hydride transfer,
      FNRox-NADPH and FNRrd-NADP+. Detectable amounts of FNRox-NADPH were found at
      equilibrium, but FNRrd-NADP+ accumulated to a small extent and quickly evolved.
      The spectral properties of both charge-transfer complexes, for the first time in
      Anabaena FNR, as well as the corresponding inter-conversion hydride transfer
      rates were obtained. The need of an adequate initial interaction between NADP+/H
      and FNR, and subsequent conformational changes, was also established by studying
      the reactions of two FNR mutants.

PMID- 17224128
TI  - A partially purified putative iron P type-ATPase mediates Fe3+-transport into
      proteoliposome.
AB  - We report that two fractions containing proteins from rat hepatocyte nuclei,
      obtained by nondenaturing gel electrophoresis, were able to bind iron and ATP,
      and to hydrolyze ATP. Electroelution of these two active fractions followed by
      SDS-PAGE analysis showed an identical protein pattern, each one containing four
      proteins in a range of 62-80 kDa. Phosphorylated protein bands were also detected
      in acid gel and disappeared after treatment with hydroxylamine/acetate or KOH,
      and upon chasing with cold ATP. A proteoliposome system, made by the
      incorporation of these partially purified protein fractions into
      phosphatidylcholine vesicles, carried out Fe(3+)-citrate uptake in a Mg(2+)-ATP
      dependent way; Fe(3+) accumulation increased with time reaching a plateau in 30
      min. Iron uptake was not supported by AMP-PNP, was partially inhibited by
      orthovanadate and was not affected by a mix of specific inhibitors of known
      ATPases. These results support our previous hypothesis that a putative nuclear
      membrane Fe(3+)-ATPase is involved in nuclear iron homeostasis.

PMID- 17224130
TI  - Infant growth, development and tooth emergence patterns: A longitudinal study
      from birth to 6 years of age.
AB  - OBJECTIVE: To test the association of child's growth/development status and
      socioeconomic variables with dental emergence patterns. DESIGN: A sample of 359
      children belonging to a birth cohort of over 5000 children born in 1993 in
      Pelotas (Brazil) was studied in 1998-1999. Previously trained observers collected
      birthweight, head circumference at birth, birth height, gestational age, smoking
      during pregnancy, child's sex and skin colour, height by age at 6 months of age,
      caries experience in the deciduous teeth, number of emerged teeth at 6 and 12
      months of age and emergence stages of the first permanent molars at 6 years of
      age. Family income, parental educational attainment and anthropometric
      measurements were collected at children's homes. Poisson regression models were
      applied in order to select best predictors of pairs of emerged teeth at 6 and 12
      months of age and emerged (yes/no) first permanent molars at 6 years of age.
      RESULTS: Children shorter than 49cm had, on average, less pairs of emerged teeth
      at 6 months of age. Twelve-month-old children with birth height < or =49cm,
      presenting height-for-age deficit at 6 months of age and the females also
      presented less pairs of emerged teeth. Stunted children at 6 months of age were
      more likely to have non-emerged first upper left and lower right permanent molars
      at 6 years of age. CONCLUSIONS: Important developmental and nutritional variables
      at birth and throughout the early life may predict the numbers of emerged teeth
      children have in their oral cavity.

PMID- 17224129
TI  - Vitamin D receptor expression by the lung micro-environment is required for
      maximal induction of lung inflammation.
AB  - Mice lacking the vitamin D receptor (VDR) are resistant to airway inflammation.
      Pathogenic immune cells capable of transferring experimental airway inflammation
      to wildtype (WT) mice are present and primed in the VDR KO mice. Furthermore, the
      VDR KO immune cells homed to the WT lung in sufficient numbers to induce symptoms
      of asthma. Conversely, WT splenocytes, Th2 cells and hematopoetic cells induced
      some symptoms of experimental asthma when transferred to VDR KO mice, but the
      severity was less than that seen in the WT controls. Interestingly,
      experimentally induced vitamin D deficiency failed to mirror the VDR KO phenotype
      suggesting there might be a difference between absence of the ligand and VDR
      deficiency. Lipopolysaccharide (LPS) induced inflammation in the lungs of VDR KO
      mice was also less than in WT mice. Together the data suggest that vitamin D and
      the VDR are important regulators of inflammation in the lung and that in the
      absence of the VDR the lung environment, independent of immune cells, is less
      responsive to environmental challenges.

PMID- 17224133
TI  - Altered brain activation pattern associated with drug-induced attenuation of
      enhanced depression-like behavior in rats bred for high anxiety.
AB  - BACKGROUND: The enhanced depression-like behavior in the forced swim test
      displayed by rats selectively bred for high anxiety-related behavior (HAB) as
      compared with their low anxiety counterparts (LAB) is abolished by chronic
      paroxetine treatment. The aim of the present study was to identify neuronal
      substrates underlying this treatment response in HABs. METHODS: The HAB rats
      received paroxetine (10 mg/kg/day) for 24 days via drinking water, and drug
      induced modulation of neuronal activation patterns in response to forced swimming
      was mapped with the expression of the immediate early gene c-Fos as marker.
      RESULTS: Chronic paroxetine treatment reduced the immobility scores during forced
      swimming, confirming the previously observed antidepressant-like effect in these
      animals, and attenuated the forced swim-induced c-Fos response in a restricted
      set (11 of 70) of brain areas. These included limbic areas such as the prelimbic
      cortex, parts of the amygdala, the bed nucleus of the stria terminalis, dorsal
      hippocampus, dorsal lateral septum as well as hypothalamic and hindbrain areas
      (dorsolateral periaqueductal gray [PAG], locus coeruleus). Untreated LAB rats,
      which displayed low depression-like behavior comparable to that of treated HABs,
      also showed low swim stress-induced c-Fos response in most of these same areas,
      further supporting an association of attenuated neuronal excitability in the
      identified areas with attenuated depression-like behavior. CONCLUSIONS: These
      findings indicate that modulation of neuronal activation in a restricted set of
      defined, mainly limbic as well as selected hypothalamic and hindbrain areas by
      paroxetine treatment is associated with the reduction of enhanced depression-like
      behavior in a psychopathological animal model.

PMID- 17224132
TI  - New insights into the efficacy of naltrexone based on trajectory-based reanalyses
      of two negative clinical trials.
AB  - BACKGROUND: The heterogeneity of clinical findings in studies evaluating the
      efficacy of naltrexone in the treatment of alcohol dependence has led to growing
      efforts to explore novel approaches to data analysis. The objective of this study
      was to identify distinct trajectories of daily drinking over time in two negative
      clinical trials and to determine whether naltrexone affected the probability to
      follow a particular trajectory. METHODS: The Veterans Affairs (VA) Cooperative
      Study #425 and the Women's Naltrexone Study failed to demonstrate efficacy on
      primary outcome variables. Separately for each study, we analyzed daily
      indicators of any drinking and heavy drinking using a semiparametric group-based
      approach. RESULTS: We estimated three distinct trajectories of daily drinking
      (both any and heavy drinking) which we described as "abstainer," "sporadic
      drinker," and "consistent drinker." Naltrexone doubled the odds of following the
      abstainer trajectory instead of the consistent drinker trajectory but did not
      significantly change the odds of following the abstainer trajectory as contrasted
      with the sporadic drinker trajectory. CONCLUSIONS: Naltrexone may have a
      clinically meaningful effect for alcohol-dependent patients with a high chance of
      consistent drinking, even in studies where it failed to show efficacy in planned
      analyses.

PMID- 17224131
TI  - Metal contaminants promote degradation of lipid/DNA complexes during
      lyophilization.
AB  - Oxidation reactions represent an important degradation pathway of nucleic acid
      based pharmaceuticals. To evaluate the role of metal contamination and chelating
      agents in the formation of reactive oxygen species (ROS) during lyophilization,
      ROS generation and the stability of lipid/DNA complexes were investigated.
      Trehalose-containing formulations were lyophilized with different levels of
      transition metals. ROS generation was examined by adding proxyl fluorescamine to
      the formulations prior to freeze-drying. Results show that ROS were generated
      during lyophilization, and both supercoil content and transfection rates
      decreased as the levels of metal-induced ROS increased. The experiments
      incorporating chelators demonstrated that some of these agents (e.g., DTPA,
      desferal) clearly suppress ROS generation, while others (e.g., EDTA) enhance ROS.
      Surprisingly, there was not a strong correlation of ROS generated in the presence
      of chelators with the maintenance of supercoil content. In this study, we
      demonstrated the adverse effects of the presence of metals (especially Fe(2+)) in
      nonviral vector formulations. While some chelators attenuate ROS generation and
      preserve DNA integrity, the effects of these additives on vector stability during
      lyophilization are difficult to predict. Further study is needed to develop
      potent formulation strategies that inhibit ROS generation and DNA degradation
      during lyophilization and storage.

PMID- 17224134
TI  - Temporal difference modeling of the blood-oxygen level dependent response during
      aversive conditioning in humans: effects of dopaminergic modulation.
AB  - BACKGROUND: The prediction error (PE) hypothesized by the temporal difference
      model has been shown to correlate with the phasic activity of dopamine neurons
      during reward learning and the blood-oxygen level dependent (BOLD) response
      during reward and aversive conditioning tasks. We hypothesized that dopamine
      would modulate the PE related signal in aversive conditioning and that
      haloperidol would reduce PE related activity, while an acute dose of amphetamine
      would increase PE related activity in the ventral striatum. METHODS: Healthy
      participants took an acute dose of amphetamine, haloperidol, or placebo. We used
      functional magnetic resonance imaging (fMRI) to measure the BOLD signal while
      they carried out an aversive conditioning task, using cutaneous electrical
      stimulation as the unconditioned stimulus (US) and yellow and blue circles as
      conditioned stimulus (CS+ and CS-, respectively). RESULTS: Prediction error
      related BOLD activity was seen only in the ventral striatum in the placebo
      subjects. The subjects given amphetamine showed a wider network of PE related
      BOLD activity, including the ventral striatum, globus pallidus, putamen, insula,
      anterior cingulate, and substantia nigra/ventral tegmental area. Haloperidol
      subjects did not show PE related activity in any of these regions. CONCLUSIONS:
      Our results provide the first demonstration that the modulation of dopamine
      transmission affects both the physiological correlates and PE related BOLD
      activity during aversive learning.

PMID- 17224135
TI  - Caudate nucleus is enlarged in high-functioning medication-naive subjects with
      autism.
AB  - BACKGROUND: Autism is defined by three symptom clusters, including repetitive and
      stereotyped behavior. Previous studies have implicated basal ganglia in these
      behaviors. Earlier studies investigating basal ganglia in autism have included
      subjects on neuroleptics known to affect basal ganglia volumes. Therefore, we
      investigated these structures in medication-naive subjects with autism. METHODS:
      Volumetric magnetic resonance measures of caudate, putamen, and nucleus accumbens
      were compared in two independent samples of medication-naive, high-functioning
      subjects with autism or Asperger syndrome: 1) 21 affected children and
      adolescents and 21 matched control subjects; and 2) 21 affected adolescents and
      young adults and 21 matched control subjects. RESULTS: Caudate nucleus was
      enlarged in both samples. This result remained significant after correction for
      total brain volume. CONCLUSIONS: These results implicate caudate nucleus in
      autism, as an enlargement of this structure was disproportional to an increase in
      total brain volume in two independent samples of medication-naive subjects with
      autism.

PMID- 17224136
TI  - Prevention of 7-ketocholesterol-induced mitochondrial damage and cell death by
      calmodulin inhibition.
AB  - Oxysterols such as 7-ketocholesterol and 25-hydroxycholesterol formed under
      enhanced oxidative stress in the brain are suggested to induce neuronal cell
      death. The present study investigated the effect of calmodulin antagonists
      (trifluoperazine, W-7 and calmidazolium) against the cytotoxicity of 7
      ketocholesterol in relation to the mitochondria-mediated cell death process and
      oxidative stress. PC12 cells exposed to 7-ketocholesterol revealed nuclear
      damage, decrease in the mitochondrial transmembrane potential, cytosolic
      accumulation of cytochrome c, activation of caspase-3, increase in the formation
      of reactive oxygen species and depletion of GSH. N-Acetylcysteine, trolox,
      carboxy-PTIO and Mn-TBAP reduced the cytotoxic effect of 7-ketocholesterol.
      Calmodulin antagonists attenuated the 7-ketocholesterol-induced nuclear damage,
      formation of the mitochondrial permeability transition and cell viability loss in
      PC12 cells. The results suggest that calmodulin antagonists may prevent the 7
      ketocholesterol-induced viability loss in PC12 cells by suppressing formation of
      the mitochondrial permeability transition, leading to the release of cytochrome c
      and subsequent activation of caspase-3. The effects seem to be ascribed to their
      depressant action on the formation of reactive oxygen species and depletion of
      GSH. The findings suggest that calmodulin inhibition may exhibit a protective
      effect against the neurotoxicity of 7-ketocholesterol.

PMID- 17224137
TI  - Unexpected regioselectivity of Humicola insolens Cel7B glycosynthase mutants.
AB  - Four Humicola insolens Cel7B glycoside hydrolase mutants have been evaluated for
      the coupling of lactosyl fluoride on O-allyl N(I)-acetyl-2(II)-azido-beta
      chitobioside. Double mutants Cel7B E197A H209A and Cel7B E197A H209G
      preferentially catalyze the formation of a beta-(1-->4) linkage between the two
      disaccharides, while single mutant Cel7B E197A and triple mutant Cel7B E197A
      H209A A211T produce predominantly the beta-(1-->3)-linked tetrasaccharide. This
      result constitutes the first report of the modulation of the regioselectivity
      through site-directed mutagenesis for an endoglycosynthase.

PMID- 17224138
TI  - Relationship between oxidative stress, lipid peroxidation, and ultrastructural
      damage in patients with coronary artery disease undergoing cardioplegic
      arrest/reperfusion.
AB  - OBJECTIVE: In animal models, formation of oxidants during postischemic
      reperfusion may exert deleterious effects ("oxidative stress"). Cardioplegic
      arrest/reperfusion during cardiac surgery might similarly induce oxidative
      stress. However, the phenomenon has not been precisely characterized in patients,
      and therefore the role of antioxidant therapy at cardiac surgery is a matter of
      debate. Thus, we wanted to ascertain whether the relationship between oxidant
      formation and development of myocardial injury also translates to the situation
      of patients subjected to cardioplegic arrest. METHODS: In 24 patients undergoing
      coronary artery bypass, trans-cardiac blood samples and myocardial biopsies were
      taken before cardioplegic arrest and again following reperfusion. RESULTS:
      Cardiac glutathione release (marker of oxidant production) was negligible at
      baseline (0.02+/-0.04 micromol/L), but it increased 15 min into reperfusion
      (1.10+/-0.40 micromol/L; p<0.05); concomitantly, myocardial concentration of the
      antioxidant ubiquinol decreased from 144.5+/-52.0 to 97.6+/-82.0 nmol/g (p<0.05).
      Although these changes document cardiac exposure to oxidants, they were not
      accompanied by evidence of injury. Neither coronary sinus blood nor cardiac
      biopsies showed increased lipid peroxide concentrations. Furthermore, electron
      microscopy showed no major ultrastructural alterations. Finally, full recovery of
      left ventricular systolic and diastolic function was observed. CONCLUSIONS:
      Careful investigation reveals that while oxidant production does occur during
      cardiac surgery in patients with chronic ischemic heart disease, cardiac
      oxidative stress may not progress through membrane damage and irreversible
      injury.

PMID- 17224139
TI  - Disparity in the induction of glutathione depletion, ROS formation, poly(ADP
      ribose) polymerase-1 activation, and apoptosis by quinonoid derivatives of
      naphthalene in human cultured cells.
AB  - The purpose of this study is to examine the differences in the induction of
      cytotoxic effects and poly(ADP-ribose) polymerase-1 activation in human MCF-7
      breast cancer cells by quinonoid derivatives of naphthalene, including 1,2
      naphthalenediol (NCAT), 1,4-naphthalenediol (NHQ), 1,2-naphthoquinone (1,2-NQ),
      and 1,4-naphthoquinone (1,4-NQ). Results from the cytotoxic response analyses in
      cells indicated that all naphthalene quinonoids induced cell death in MCF-7 cells
      at concentrations ranging from 0.1 to 100microM where NHQ and 1,4-NQ were more
      efficient than NCAT and 1,2-NQ in the induction of cell death. Results from
      Western blot analyses confirmed that treatment of cells with NCAT and NHQ
      resulted in up-regulation of p53 protein expression and a significant shift in
      bax/bcl2 ratio, suggesting the induction of p53-dependent apoptosis in MCF-7
      cells. Additionally, we observed that all naphthalene quinonoids induced
      increases in reactive oxygen species (ROS) formation and glutathione (GSH)
      depletion in MCF-7 cells. The induction of ROS formation and GSH depletion in
      cells by naphthalene quinonoids decreases in the rank order 1,4-NQ>NHQ>1,2-NQ
      approximately equal to NCAT. Further investigation indicated that least-squares
      estimates of the overall rates of elimination (k(e)) of naphthalene quinonoids in
      MCF-7 cells decreased in the rank order 1,4-NQ>1,2-NQ>NHQ>NCAT. Values of k(e)
      were estimated to be between 0.280h(-1)(T(1/2)=151min) and 13.8h(
      1)(T(1/2)=3.05min). These results provide evidence that the para-isomeric form of
      naphthalene quinonoids tend to induce acute production of ROS and alterations in
      intracellular redox status in cells, leading to the subsequent cell death.
      Further, all naphthalene quinonoids induced decreases in intracellular NAD(P)H
      and NAD(+) in MCF-7 cells at non-cytotoxic concentrations. The reduction of
      intracellular NAD(P)H in cells exposed to NCAT and 1,2-NQ was blocked by two
      types of poly(ADP-ribose) polymerase (PARP) inhibitors whereas PARP inhibitors
      did not prevent the reduction of NAD(P)H in cells exposed to NHQ and 1,4-NQ.
      Further investigation confirmed that increases in the number of DNA single-strand
      breaks were detected in MCF-7 cells exposed to NCAT and 1,2-NQ as measured by the
      single-cell gel electrophoresis (Comet) assay whereas NHQ and 1,4-NQ did not
      induce increases in the number of single-strand breaks in MCF-7 cells. Overall,
      results from our investigation suggest that while NHQ and 1,4-NQ are more
      efficient in the induction of cell death, NCAT and 1,2-NQ are prone to induce
      depletion of NAD(P)H and NAD(+) mediated by PARP-1 activation through formation
      of DNA single-strand breaks in human cultured cells.

PMID- 17224140
TI  - Formation of depurinating N3adenine and N7guanine adducts after reaction of 1,2
      naphthoquinone or enzyme-activated 1,2-dihydroxynaphthalene with DNA.
      Implications for the mechanism of tumor initiation by naphthalene.
AB  - Naphthalene is considered by the US Environmental Protection Agency to be a
      carcinogenic compound based on inhalation studies in rats. The primary metabolite
      of naphthalene is naphthalene 1,2-arene oxide. This unstable intermediate can
      lead to formation of 1-naphthol and naphthalene-1,2-dihydrodiol. Secondary
      metabolites include 1,2-dihydroxynaphthalene (1,2-DHN), which can be further
      oxidized to 1,2-naphthoquinone (1,2-NQ). Based on the metabolism of naphthalene
      and its similarity to the metabolic activation of carcinogenic natural estrogens,
      synthetic estrogens and benzene, we hypothesize that naphthalene is activated to
      initiate cancer by reaction of 1,2-NQ with DNA to form the depurinating adducts
      1,2-DHN-4-N3Ade and 1,2-DHN-4-N7Gua. These adducts were synthesized by reaction
      of 1,2-NQ with Ade or dG in acetic acid/water/DMF (1:1:1). 1,2-NQ was reacted
      with DNA, and the depurinating 1,2-DHN-4-N3Ade and 1,2-DHN-4-N7Gua adducts were
      analyzed by ultraperformance liquid chromatography/tandem mass spectrometry and
      HPLC with electrochemical detection. After the reaction of 1,2-NQ with DNA, the
      N3Ade and N7Gua adducts were found. Similarly, when 1,2-DHN was activated by
      tyrosinase in the presence of DNA, higher amounts of the N3Ade and N7Gua adducts
      were detected. These same adducts were also formed when 1,2-DHN was activated by
      prostaglandin H synthase or 3-methylcholanthrene-induced rat liver microsomes in
      the presence of DNA. These depurinating adducts are analogous to those obtained
      from the ortho-quinones of natural estrogens, synthetic estrogens and benzene.
      These results suggest that reaction of ortho-quinones with DNA by 1,4-Michael
      addition is a general mechanism of weak carcinogenesis that occurs with
      naphthalene and a number of other aromatic compounds.

PMID- 17224142
TI  - Vasopressin V1A receptor enhances baroreflex via the central component of the
      reflex arc.
AB  - The neurohypophyseal peptide [Arg(8)]-vasopressin (AVP) exerts its physiological
      actions via 3 distinct receptor isoforms designated V1A, V1B, and V2. We recently
      showed that V1A receptor was involved in the baroreflex control of heart rate
      using V1A receptor knockout mice. The present study was undertaken to further
      clarify this finding. In conscious mice, resting blood pressure of the knockout
      group was lower than that of the wild-type group (wild-type, 108+/-2.0 mm Hg;
      knockout, 98+/-3.8 mm Hg; n=6-7) without notable change in heart rate. Although
      phenylephrine and nitroprusside-induced changes in blood pressure did not differ
      in these strains, the subsequent bradycardia and tachycardia were markedly
      blunted in the knockout mice (mean slopes for baroreflex curve after
      phenylephrine treatment; wild-type, -5.65+/-0.30 bpm/mm Hg; knockout, -3.97+/
      0.52 bpm/mm Hg; those after nitroprusside treatment; wild-type, -0.51+/-0.10
      bpm/mm Hg; knockout, -0.18+/-0.05 bpm/mm Hg; n=6-7). Under urethane anesthesia
      (1.0-1.2 g/kg, i.p.), electrical stimulation of the vagal afferent nerve evoked
      frequency-dependent hypotension and bradycardia in the wild-type mice. In
      contrast, in the knockout mice such stimulation induced a pressor, not a
      depressor, response and diminished bradycardia. Moreover, electrical stimulation
      induced hemodynamic changes through the vagal afferent nerve in the wild-type
      mice were significantly attenuated by pretreatment with intravenously
      administered V1A receptor antagonist d(CH(2))(5)Tyr(Me)AVP. Electrical
      stimulation of the vagal efferent nerve-induced hemodynamic changes (depressor
      and bradycardia) and chronotropic responses to adrenergic and cholinergic stimuli
      were not different between the 2 strains. These results suggest that the V1A
      receptor in the central nervous system is involved in the regulation of the heart
      rate via the baroreflex arc.

PMID- 17224141
TI  - C2H2 zinc finger-SET histone methyltransferase is a plant-specific chromatin
      modifier.
AB  - Histone modification represents a universal mechanism for regulation of
      eukaryotic gene expression underlying diverse biological processes from neuronal
      gene expression in mammals to control of flowering in plants. In animal cells,
      these chromatin modifications are effected by well-defined multiprotein complexes
      containing specific histone-modifying activities. In plants, information about
      the composition of such co-repressor complexes is just beginning to emerge. Here,
      we report that two Arabidopsis thaliana factors, a SWIRM domain polyamine oxidase
      protein, AtSWP1, and a plant-specific C2H2 zinc finger-SET domain protein, AtCZS,
      interact with each other in plant cells and repress expression of a negative
      regulator of flowering, FLOWERING LOCUS C (FLC) via an autonomous, vernalization
      independent pathway. Loss-of-function of either AtSWP1 or AtCZS results in
      reduced dimethylation of lysine 9 and lysine 27 of histone H3 and
      hyperacetylation of histone H4 within the FLC locus, in elevated FLC mRNA levels,
      and in moderately delayed flowering. Thus, AtSWP1 and AtCZS represent two main
      components of a co-repressor complex that fine tunes flowering and is unique to
      plants.

PMID- 17224143
TI  - Identification of a pyridoxine (pyridoxamine) 5'-phosphate oxidase from
      Arabidopsis thaliana.
AB  - Pyridoxine (pyridoxamine) 5'-phosphate oxidase (PPOX) catalyzes the oxidative
      conversion of pyridoxamine 5'-phosphate (PMP) or pyridoxine 5'-phosphate (PNP) to
      pyridoxal 5'-phosphate (PLP). The At5g49970 gene of Arabidopsis thaliana shows
      homology to PPOX's from a number of organisms including the Saccharomyces
      cerevisiae PDX3 gene. A cDNA corresponding to putative A. thaliana PPOX (AtPPOX)
      was obtained using reverse transcriptase-polymerase chain reaction and primers
      landing at the start and stop codons of At5g49970. The putative AtPPOX is 530
      amino acid long and predicted to contain three distinct parts: a 64 amino acid
      long N-terminal putative chloroplast transit peptide, followed by a long Yjef_N
      domain of unknown function and a C-terminal Pyridox_oxidase domain. Recombinant
      proteins representing the C-terminal domain of AtPPOX and AtPPOX without transit
      peptide were expressed in E. coli and showed PPOX enzyme activity. The PDX3
      knockout yeast deficient in PPOX activity exhibited sensitivity to oxidative
      stress. Constructs of AtPPOX cDNA of different lengths complemented the PDX3
      knockout yeast for oxidative stress. The role of the Yjef_N domain of AtPPOX was
      not determined, but it shows homology with a number of conserved hypothetical
      proteins of unknown function.

PMID- 17224144
TI  - New Hampshire House Bill 1719-FN. "An act defining human life as beginning at the
      moment of fertilization for the purposes of prenatal, pregnancy, and maternity
      services and programs".
AB  - Recently, the author was asked by the New Hampshire State Medical Society to
      testify before the State of New Hampshire's House Judiciary Committee, to address
      a bill that would establish the definition of when human life begins. Other
      states, such as South Dakota, recently passed a ban on abortion. Such legislation
      will severely limit a woman's ability to exercise her right to terminate her
      pregnancy. With the present composition of the US Supreme Court, it seems
      possible that in the not-too-distant future there will be a successful challenge
      to Roe v Wade. It is important that as health care providers we take the time to
      educate our public officials and general citizenry about the complexity of such
      issues. The subsequent editorial will paraphrase the statement that was
      delivered. Fortunately, the bill was defeated.

PMID- 17224145
TI  - Graduated Embryo Score and soluble human leukocyte antigen-G expression improve
      assisted reproductive technology outcomes and suggest a basis for elective single
      embryo transfer.
AB  - OBJECTIVE: To evaluate assisted reproductive technology (ART) outcomes by using
      Graduated Embryo Score (GES) and soluble human leukocyte antigen-G (sHLA-G)
      expression to select embryos for transfer on day 3. DESIGN: Prospective cohort.
      SETTING: Private practice. PATIENT(S): Women undergoing fresh ART cycles (n =
      209). INTERVENTION(S): In vitro fertilization using standard protocols. Embryos
      scoring GES of > or =70 using were selected for transfer on the basis of sHLA-G
      expression in the culture media on day 2. MAIN OUTCOME MEASURE(S): Pregnancy,
      implantation, and multiple-gestation rates. RESULT(S): Ongoing gestations
      increased with the number of embryos expressing sHLA-G (37%, 42%, 58%, and 56%
      with 0, 1, 2, or 3 sHLA-G(+), respectively). With at least two sHLA-G(+) embryos,
      ongoing gestation and implantation rates were higher than those with fewer than
      two sHLA-G(+). Differences were even higher for women aged < or =37 years. With
      at least two sHLA-G(+) embryos, the odds ratio (95% confidence interval) was 1.59
      (1.51-1.68) for ongoing gestation compared with the case of fewer than two sHLA
      G(+). Age was the most important predictor of outcome; the odds ratio (95%
      confidence interval) was 2.07 (1.98-2.16) for ongoing gestation in women aged <
      or =37 years with at least two sHLA-G(+) embryos, compared with the case of women
      aged 38-40 years. CONCLUSION(S): Day 3 embryo transfer using GES and sHLA-G
      improves ART outcomes by increasing predictive accuracy. High twin rates suggest
      that couples with at least two sHLA-G(+) embryos consider elective single-embryo
      transfer.

PMID- 17224146
TI  - Early pregnancy loss in women stimulated with gonadotropin-releasing hormone
      antagonist protocols according to oral contraceptive pill pretreatment.
AB  - OBJECTIVE: To evaluate and compare the risk of early pregnancy loss in patients
      stimulated with GnRH antagonist protocols according to oral contraceptive pill
      (OCP) pretreatment. DESIGN: Retrospective case-control study. SETTING: Instituto
      Valenciano de Infertilidad. University of Valencia. Spain. PATIENT(S): One
      thousand five hundred thirty-nine patients, aged <36, stimulated with GnRH
      antagonists for IVF between January 1, 2000 and November 1, 2005.
      INTERVENTION(S): Reproductive outcome was compared based on the application (or
      not) of OCP pretreatment: 944 women were included in the OCP group and 595 in the
      non-OCP group. The Student's t test was used for statistics. MAIN OUTCOME
      MEASURE(S): Pregnancy, biochemical pregnancy, ectopic pregnancy, early clinical
      pregnancy loss, early pregnancy loss, and ongoing pregnancy rates. RESULT(S): No
      significant differences were observed in any of the outcome parameters. Early
      pregnancy loss rates were similar: 23% in the OCP pretreatment group versus 19.2%
      in the non-OCP pretreatment group. However, longer periods of ovarian stimulation
      and higher doses of gonadotropins needed to be employed in the OCP group.
      CONCLUSION(S): There is not sufficient evidence to confirm OCP pretreatment as a
      risk factor for miscarriage in patients stimulated with GnRH antagonist
      protocols.

PMID- 17224148
TI  - Effect of atosiban on rabbit embryo development and human sperm motility.
AB  - OBJECTIVE: To investigate embryotoxic potential and effects on human sperm
      motility of the mixed vasopressin V(1a)/oxytocin receptor antagonist atosiban
      considered for novel indication of improvement of uterine receptivity in embryo
      transfer recipients. DESIGN: One-cell rabbit embryo bioassay and human sperm
      motility bioassay were performed in control media or in media containing
      atosiban. SETTING: Private center of reproductive medicine and academic research
      institute of reproduction biotechnology. ANIMAL(S): Rabbit females (New Zealand
      and California, N = 15) aged 4.5-6.5 months. INTERVENTION(S): In vitro exposure
      of one-cell rabbit embryos and human sperm to atosiban in the range of
      therapeutic concentrations clinically occurring in human beings. MAIN OUTCOME
      MEASURE(S): Embryo development and sperm motility. RESULT(S): Preimplantation
      development of one-cell rabbit embryos was not affected by atosiban in the
      concentrations < or =15,000 nM, which was 50-fold higher than the mean plasma
      concentration reached during regular therapy (300 nM). Atosiban did not affect
      human sperm motility in concentrations of < or =3,000 nM, in other words, 10
      times the human mean plasma concentration. CONCLUSION(S): Clinical application of
      atosiban in the proposed indication may be safe for embryos because it is
      compatible with preimplantation rabbit embryo development and human sperm
      motility.

PMID- 17224147
TI  - The presence of pinopodes in the human endometrium does not delineate the
      implantation window.
AB  - OBJECTIVE: To assess pinopode formation in human endometrium during the luteal
      phase of the menstrual cycle and in the first trimester of pregnancy. DESIGN:
      Prospective clinical study. SETTING: Outpatient infertility clinics and
      outpatient family planning clinic. PATIENT(S): Thirty-two regularly cycling
      infertile women, 15 regularly cycling fertile women, 9 women receiving elective
      termination of pregnancy, and 1 woman receiving GnRH agonist and hormone therapy
      addback. INTERVENTION(S): Endometrial tissue was collected by suction pipelle and
      examined by scanning electron microscopy for pinopode formation. MAIN OUTCOME
      MEASURE(S): Endometrial tissue was scored (0, 1, 2, 3, or 4) depending on the
      percentage of the surface covered in pinopodes (from 0% to >20% of 100 fields).
      RESULT(S): Pinopodes were present throughout the luteal phase of the menstrual
      cycle, up to the 11th week of pregnancy, and in the endometrium of the woman on
      GnRH agonist and hormone therapy. CONCLUSION(S): Pinopodes can be detected in the
      progesterone-exposed endometrium for an extended period of time, in
      contradistinction to the perception that they are markers for the implantation
      window in the human endometrium.

PMID- 17224150
TI  - The accelerated pace of pharma abandonment of research and development in family
      planning and fertility: will reproductive health technology be frozen in time?

PMID- 17224149
TI  - The progesterone receptor gene polymorphism, PROGINS, may be a factor related to
      the development of uterine fibroids.
AB  - OBJECTIVE: To assess the possible association between the polymorphic allele of
      the progesterone receptor gene, named PROGINS, and uterine leiomyomas. DESIGN:
      Case-control study. SETTING: Department of Gynecology. Teaching hospital.
      PATIENT(S): One hundred twenty-two premenopausal women with fibroids and 125
      postmenopausal controls not presenting the disease. INTERVENTION(S): The subjects
      were classified as White or non-White (Black and Mulatto) and the progesterone
      receptor genotyping was performed, with DNA extracted from uterus in cases and
      from peripheric blood in controls and submitted to polymerase chain reaction
      (PCR) and agarose gel electrophoresis. MAIN OUTCOME MEASURE(S): The presence of
      the PROGINS allele was recorded, and its frequency as well as the genotypic
      distribution among cases and controls were compared according to race. RESULT(S):
      PROGINS-positive genotypes (heterozygous or mutant homozygous) were found in 19%
      of White and 11% of non-White women, and allelic frequency of PROGINS in the
      groups was 10.4% and 6.2%, respectively. Comparing patients and controls, we
      observed a significant difference among non-White women, both regarding presence
      of PROGINS-positive genotypes (4.9% vs. 25%, respectively), and PROGINS allele
      frequency (3.3% vs. 12.5%, respectively). There was no significant difference in
      PROGINS-positive genotypes among White cases and controls (16.4% vs. 20.6%,
      respectively), and in their allelic frequency (8.2% vs. 11.9%, respectively). The
      odds ratio showed reduced risk of fibroids related to PROGINS-positive genotypes
      in non-White women (odds ratio = 0.16, 95% confidence interval: 0.04-0.66), but
      not among White subjects (odds ratio = 0.76, 95% confidence interval: 0.33-1.74).
      CONCLUSION(S): The PROGINS polymorphism revealed to be protective in terms of
      uterine fibroids in Brazilian non-White women.

PMID- 17224152
TI  - Acute effects of metformin therapy include improvement of insulin resistance and
      ovarian morphology.
AB  - OBJECTIVE: To evaluate the acute effects of metformin therapy on biochemical
      markers and polycystic ovarian morphology among insulin-resistant (IR) and
      noninsulin-resistant (NIR) patients with polycystic ovary syndrome (PCOS).
      DESIGN: Prospective interventional study. SETTING: Reproductive endocrinology
      clinic in a university hospital. PATIENT(S): Five IR and five NIR patients with
      PCOS. The mean age of patients was 29.5 +/- 4.8 years (range, 23-36 years).
      INTERVENTION: Metformin therapy, using 850 mg orally per day for 1 week. MAIN
      OUTCOME MEASURE(S): Serum levels of T, FSH, and LH, fasting glucose/insulin
      ratio, levels of anti-Mullerian hormone (AMH) and inhibin B, and antral follicle
      count. RESULT(S): Levels of AMH and inhibin B were statistically significantly
      higher in patients with PCOS compared to controls (2.81 +/- 1.79 ng/mL versus
      0.95 +/- 1.17 ng/mL, and 56.24 +/- 29.39 pg/mL versus 17.89 +/- 12.87 pg/mL,
      respectively). Levels of AMH and inhibin B were similar among IR and NIR patients
      with PCOS (2.77 +/- 1.92 ng/mL versus 2.85 +/- 1.89 ng/mL, and 53.96 +/- 28.58
      pg/mL versus 58.51 +/- 33.28 pg/mL, respectively). One week of metformin therapy
      did not alter either AMH or inhibin B levels. However, there was a statistically
      significant increase in glucose/insulin ratios (4.59 +/- 1.57 versus 6.35 +/-
      3.6), and a significant decrease in the number of antral follicles after 1 week
      of metformin therapy (38.8 +/- 19.3 versus 23.1 +/- 7.4). CONCLUSION(S): Levels
      of AMH and inhibin B are significantly increased in patients with PCOS compared
      to controls, but are not associated with insulin resistance. Low-dose metformin
      therapy improves IR and polycystic ovary morphology, even though levels of T,
      AMH, and inhibin B remain unchanged.

PMID- 17224151
TI  - Contrasting patterns in in vitro fertilization pregnancy rates among fresh
      autologous, fresh oocyte donor, and cryopreserved cycles with the use of day 5 or
      day 6 blastocysts may reflect differences in embryo-endometrium synchrony.
AB  - OBJECTIVE: To compare the effect of day 5 and day 6 blastocyst transfers on
      patterns of implantation rates and pregnancy rates (PRs) among fresh autologous,
      oocyte donor, and frozen ET (FET) cycles. DESIGN: Retrospective study. SETTING:
      Private fertility center. PATIENT(S): The study included 377 fresh autologous
      cycles, 106 autologous FET cycles, and 56 fresh oocyte donor cycles.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation rates and clinical
      PRs. RESULT(S): The clinical PR for day 5 blastocyst transfers was higher than
      for day 6 blastocyst transfers in fresh autologous cycles (PRs, 51.0% and 33.3%,
      respectively). However, there was no significant difference between transfers of
      blastocysts cryopreserved on day 5 and day 6 in FET cycles (PRs, 63.6% and 58.9%,
      respectively). Furthermore, day 6 blastocyst transfers significantly outperformed
      day 5 transfers in donor cycles (PRs, 63.0% and 86.2%, respectively), a reversal
      of the pattern seen in the fresh autologous cycles. Day 6 blastocysts were
      associated with a significantly greater PR in FET cycles than in fresh autologous
      cycles (58.9% and 33.3%, respectively). CONCLUSION(S): The superior PRs with day
      5 blastocyst transfers in fresh autologous cycles and with day 6 blastocysts in
      donor cycles may have resulted from better synchrony with endometrial
      development. This was further supported by the superior performance of day 6
      blastocysts in FET cycles relative to their fresh counterparts. Similar PRs with
      cryopreserved day 5 and day 6 blastocysts in FET cycles may reflect that, in
      these cycles, day 5 and day 6 blastocysts had equivalent quality and similar
      synchrony with the endometrium.

PMID- 17224153
TI  - Successful pregnancy rates achieved with day 4 embryo transfers.
AB  - OBJECTIVE: To assess the success of day 4 embryo transfers (ETs) following IVF at
      one institution. DESIGN: Retrospective analysis. SETTING: A university hospital
      IVF program. PATIENT(S): Two hundred nondonor, fresh IVF cycles. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE: Outcomes of IVF. Outcome assessments after day 4 ETs
      included rates of implantation, clinical pregnancy, and singleton and multiple
      live births. RESULT(S): The overall live-birth rate was 54.4%. Implantation rates
      were highest in younger age groups, and similar in patients 35-40 years of age.
      Pregnancy and live-birth rates were similar across all age groups up to age 40
      years. Multiple gestations were highest in women < or =40 years of age.
      CONCLUSION: Acceptable pregnancy rates can be achieved with day 4 ETs.

PMID- 17224154
TI  - Using bacteria to express and display anti-Plasmodium molecules in the mosquito
      midgut.
AB  - Bacteria capable of colonizing mosquito midguts are attractive vehicles for
      delivering anti-malaria molecules. We genetically engineered Escherichia coli to
      display two anti-Plasmodium effector molecules, SM1 and phospholipase-A(2), on
      their outer membrane. Both molecules significantly inhibited Plasmodium berghei
      development when engineered bacteria were fed to mosquitoes 24h prior to an
      infective bloodmeal (SM1=41%, PLA2=23%). Furthermore, prevalence and numbers of
      engineered bacteria increased dramatically following a bloodmeal. However, E.
      coli survived poorly in mosquitoes. Therefore, Enterobacter agglomerans was
      isolated from mosquitoes and selected for midgut survival by multiple passages
      through mosquitoes. After four passages, E. agglomerans survivorship increased
      from 2 days to 2 weeks. Since E. agglomerans is non-pathogenic and widespread, it
      is an excellent candidate for paratransgenic control strategies.

PMID- 17224155
TI  - Experimental infections of the monogenean Gyrodactylus turnbulli indicate that it
      is not a strict specialist.
AB  - Parasites represent a threat to endangered fish species, particularly when the
      parasite can host switch and the new host is vulnerable. If the parasite is
      highly host specific then successful host switching should be a rare occurrence;
      however, the host range of many parasites which are assumed to be specialists has
      never been tested. This includes the monogenean Gyrodactylus turnbulli, a well
      studied ectoparasite found caudally on its known host, the guppy, Poecilia
      reticulata. In this study, we monitored parasite establishment and reproduction
      on a range of poeciliids and more distantly related fish. Individually maintained
      fish were experimentally infected with a single parasite and monitored daily to
      establish whether G. turnbulli could survive and reproduce on other fish species.
      Gyrodactylus turnbulli can infect a wider range of hosts than previously
      considered, highlighting the fact that host specificity can never be assumed
      unless experimentally tested. Our findings also have significant implications for
      parasite transmission to novel hosts and provide further insight into the
      evolutionary origins of this ubiquitous group of fish pathogens. Previous
      molecular evidence indicates that host switching is the key mechanism for
      speciation within the genus Gyrodactylus. Until recently, most Gyrodactylus spp.
      were assumed to be narrowly host specific. However, our findings suggest that
      even so-called specialist species, such as G. turnbulli, may represent a threat
      to vulnerable fish stocks. In view of the potential importance of host switching
      under artificial conditions, we propose to describe this as 'artificial
      ecological transfer' as opposed to 'natural ecological transfer', host switching
      under natural conditions.

PMID- 17224156
TI  - Pregnancy-associated malaria: parasite binding, natural immunity and vaccine
      development.
AB  - Humans living in areas of high malaria transmission gradually acquire, during the
      early years of life, protective clinical immunity to Plasmodium falciparum,
      limiting serious complications of malaria to young children. However, pregnant
      women become more susceptible to severe P. falciparum infections during their
      first pregnancy. Pregnancy associated malaria is coupled with massive
      accumulation of parasitised erythrocytes and monocytes in the placental
      intervillous blood spaces, contributing to disease and death in pregnant women
      and developing infants. Indirect evidence suggests that prevention may be
      possible by vaccinating women of childbearing age before their first pregnancy.
      This review aims to introduce the reader to the implications of malaria infection
      during pregnancy and to analyse recent findings towards the identification and
      characterisation of parasite encoded erythrocyte surface proteins expressed in
      malaria-infected pregnant women that are likely targets of protective immunity
      and have potential for vaccine development.

PMID- 17224158
TI  - Experimental validation of intact and implanted distal femur finite element
      models.
AB  - Four finite element (FE) models of intact and distal femur of knee replacements
      were validated relative to measured bone strains. FE models of linear
      tetrahedrons were used. Femoral replacements with cemented stemless, cemented and
      noncemented femoral stems of the PFC Sigma Modular Knee System were analyzed.
      Bone strains were recorded at ten locations on the cortex. The magnitude of the
      FE bone strains corresponded to the mean measured strains, with an overall
      agreement of 10%. Linear regression between the FE and mean experimental strains
      produced slopes between 0.94 and 1.06 and R(2) values between 0.92 and 0.99. RSME
      values were less than 12%. The FE models were able to adequately replicate the
      mechanical behavior of distal femur reconstructions.

PMID- 17224159
TI  - Use of specially designed columns for antioxidants and antimicrobials enrichment
      by preparative supercritical fluid chromatography.
AB  - A new, specially designed column has been developed for fractionation of
      supercritical fluid extract of rosemary by using a preparative supercritical
      fluid chromatography system (Prep-SFC). The column evaluated in this work was
      prepared using a new packing method consisting of a combination of slurry and
      supercritical CO2 with commercial silica particles coated with a stationary phase
      commonly used in gas chromatography, such as SE-54 (5% phenyl-, 95%
      methylsilicone). The new packing procedure provided columns with reasonable
      efficiencies, with high stability and useful at high-pressure range. A 25 cm x 10
      mm i.d. column packed with silica particles coated with 3% of SE-54 was prepared,
      and its separation power was tested for isolating fractions with high antioxidant
      and/or antimicrobial activity from a supercritical rosemary extract. The SFC
      conditions were selected based on a previous work done with a commercial LC-Diol
      packed column (130 bar, 80 degrees C), and different percentages of modifier in
      the mobile phase were tested (5 and 10%). Two cyclones were employed to collect
      the fractions which were then characterized by HPLC-diode array detection (DAD),
      GC, and in vitro antioxidant and antimicrobial assays. The use of coated packed
      columns allowed the fractionation of a complex mixture of rosemary supercritical
      extract with a minimum amount of modifier in the mobile phase (5% ethanol). At
      the optimum conditions it was possible to obtain two very active fractions in
      terms of antioxidant and antimicrobial activity, with no residual rosemary aroma
      and with improved activities compared to the original supercritical extract.

PMID- 17224160
TI  - Separation of solanesol in tobacco leaves extract by slow rotary counter-current
      chromatography using a novel non-aqueous two-phase solvent system.
AB  - Non-aqueous solvent system composed of sunflower oil-ethanol was found to be
      suitable for the separation of lower polarity components. Employing this solvent
      system, 3 g of tobacco leaves extract containing 15% solanesol was separated
      using a slow rotary counter-current chromatograph equipped with an 1100 mL column
      made of 5.7 mm I.D. convoluted PTFE tube. The separation yielded 1.5 g of yellow
      oily product in which solanesol occupied 26.8% determined by HPLC. The tobacco
      tar and other main impurities in the tobacco leaves extract were removed after
      slow rotary counter-current chromatographic separation. The separation processing
      may be developed as a technique for producing a solanesol product with food
      grade.

PMID- 17224157
TI  - Differential effects of AT1 receptor and Ca2+ channel blockade on
      atherosclerosis, inflammatory gene expression, and production of reactive oxygen
      species.
AB  - Angiotensin II receptor blockade has been shown to inhibit atherosclerosis in
      several different animal models. We sought to determine if this effect was the
      result of blood pressure reduction per se or a result of the anti-inflammatory
      effects of receptor blockade. ApoE-deficient mice were fed a high fat diet and
      treated with either an angiotensin II receptor antagonist, candesartan (0.5
      mg/kg/day, s.c.) or a calcium channel blocker, amlodipine (7.5 mg/kg/day, mixed
      with food). Atherosclerotic lesion area, aortic inflammatory gene expression as
      well as aortic H2O2 and superoxide production were assayed. We found that
      candesartan but not amlodipine treatment dramatically attenuated the development
      of atherosclerosis despite a similar reduction in blood pressure. Similarly,
      candesartan treatment inhibited aortic expression of inflammatory genes and
      production of reactive oxygen species, effects not seen with amlodipine. These
      data demonstrate that angiotensin II receptor blockade inhibits atherosclerosis
      by reducing vascular oxidative stress and inflammatory gene production
      independent of blood pressure reduction.

PMID- 17224161
TI  - Biological and molecular studies of a cypovirus from the black fly Simulium
      ubiquitum (Diptera: Simuliidae).
AB  - A cypovirus from the black fly Simulium ubiquitum (SuCPV) was isolated and
      examined using biological and molecular techniques. SuCPV produces small
      (typically 0.25mum), polyhedral shaped inclusion bodies (polyhedra), in which the
      virus particles become multiply embedded. SuCPV is the third cypovirus isolated
      from Diptera, but the first from Simuliidae that has been characterized using
      molecular analyses. SuCPV has a genome composed of 10 segments of dsRNA, with an
      electrophoretic migration pattern that is different from those of recent UsCPV-17
      and CrCPV-17 isolates from the mosquitoes Uranotaenia sapphirina and Culex
      restuans, respectively. The SuCPV electropherotype appears to show significant
      differences from those of the previously characterized lepidopteran cypoviruses.
      Sequence analysis of SuCPV segment 10 shows that it is unrelated to either of the
      two CPV isolates from Diptera or to the CPV species for which Seg-10 has been
      previously characterized from Lepidoptera. A comparison of the terminal regions
      of SuCPV genome segments to those of CPV-1, 2, 4, 5 14, 15, 16, 17, 18, and 19
      also revealed only low levels of conservation. We therefore, propose that SuCPV
      is classified within a new Cypovirus species, which we have tentatively
      identified as Cypovirus-20. We have therefore referred to this virus isolate as
      S. ubiquitum CPV-20 (SuCPV-20).

PMID- 17224163
TI  - Octameric structure of the human bifunctional enzyme PAICS in purine
      biosynthesis.
AB  - Phosphoribosylaminoimidazole carboxylase/phosphoribosylaminoimidazole
      succinocarboxamide synthetase (PAICS) is an important bifunctional enzyme in de
      novo purine biosynthesis in vertebrate with both 5-aminoimidazole ribonucleotide
      carboxylase (AIRc) and 4-(N-succinylcarboxamide)-5-aminoimidazole ribonucleotide
      synthetase (SAICARs) activities. It becomes an attractive target for rational
      anticancer drug design, since rapidly dividing cancer cells rely heavily on the
      purine de novo pathway for synthesis of adenine and guanine, whereas normal cells
      favor the salvage pathway. Here, we report the crystal structure of human PAICS,
      the first in the entire PAICS family, at 2.8 A resolution. It revealed that eight
      PAICS subunits, each composed of distinct AIRc and SAICARs domains, assemble a
      compact homo-octamer with an octameric-carboxylase core and four symmetric
      periphery dimers formed by synthetase domains. Based on structural comparison and
      functional complementation analyses, the active sites of SAICARs and AIRc were
      identified, including a putative substrate CO(2)-binding site. Furthermore, four
      symmetry-related, separate tunnel systems in the PAICS octamer were found that
      connect the active sites of AIRc and SAICARs. This study illustrated the
      octameric nature of the bifunctional enzyme. Each carboxylase active site is
      formed by structural elements from three AIRc domains, demonstrating that the
      octamer structure is essential for the carboxylation activity. Furthermore, the
      existence of the tunnel system implies a mechanism of intermediate channeling and
      suggests that the quaternary structure arrangement is crucial for effectively
      executing the sequential reactions. In addition, this study provides essential
      structural information for designing PAICS-specific inhibitors for use in cancer
      chemotherapy.

PMID- 17224162
TI  - Systematic RNAi studies on the role of Sp/KLF factors in globin gene expression
      and erythroid differentiation.
AB  - Sp/KLF family of factors regulates gene expression by binding to the CACCC/GC/GT
      boxes in the DNA through their highly conserved three zinc finger domains. To
      investigate the role of this family of factors in erythroid differentiation and
      globin gene expression, we first measured the expression levels of selected
      Sp/KLF factors in primary cells of fetal and adult stages of erythroid
      development. This quantitative analysis revealed that their expression levels
      vary significantly in cells of either stages of the erythroid development.
      Significant difference in their expression levels was observed between fetal and
      adult erythroid cells for some Sp/KLF factors. Functional studies using RNA
      interference revealed that the silencing of Sp1 and KLF8 resulted in elevated
      level of gamma globin expression in K562 cells. In addition, K562 cells become
      visibly red after Sp1 knockdown. Benzidine staining revealed significant
      hemoglobinization of these cells, indicating erythroid differentiation. Moreover,
      the expression of PU.1, ETS1 and Notch1 is significantly down-regulated in the
      cells that underwent erythroid differentiation following Sp1 knockdown.
      Overexpression of PU.1 or ETS1 efficiently blocked the erythroid differentiation
      caused by Sp1 knockdown in K562 cells. The expression of c-Kit, however, was
      significantly up-regulated. These data indicate that Sp1 may play an important
      role in erythroid differentiation.

PMID- 17224164
TI  - Mobile phones are good for you, p<0.36! Observations on Keetley, Wood, Spong and
      Stough (2006).
AB  - Keetley et al. [Keetley, V., Wood, A. W., Spong, J., & Stough, C. (2006).
      Neuropsychological sequelae of digital mobile phone exposure in humans.
      Neuropsychologia, 44, 1843-1848] report a study into the effects of mobile phones
      on a variety of cognitive tasks. They report that the presence of an active
      mobile phone reduces performance on some tasks but, surprisingly, improved
      performance on others. Bonferroni correction of this multi-hypothesis exploratory
      research, however, reveals that none of the findings reach normally accepted
      levels of significance. The results of the study remain interesting in suggesting
      hypotheses for further research, however, care must be taken if making
      conclusions based on this research.

PMID- 17224165
TI  - Effective heart disease prevention: lessons from a qualitative study of user
      perspectives in Bangladeshi, Indian and Pakistani communities.
AB  - OBJECTIVES: Coronary heart disease (CHD) has a high mortality, incidence and
      prevalence among Indian, Pakistani and Bangladeshi communities in the UK,
      indicating the need for effective heart disease prevention initiatives for these
      communities. This paper considers how service user perspectives can be used to
      develop effective, culturally focused CHD prevention interventions for these
      target groups by addressing identified barriers, including deeply held cultural
      beliefs. STUDY DESIGN: A qualitative research study, using a longitudinal action
      research approach. METHODS: This was a community-based study in Edinburgh. Six
      focus group discussions--two for each community--were organized with participants
      from these communities at the beginning of the project. A further six focus group
      discussions for the same communities were organized six months later. RESULTS:
      Over the period examined, participants reported varying changes in levels of
      knowledge relating to the nature, causes and symptoms of CHD. Some participants
      reported taking slight to significant steps to reduce or prevent heart disease,
      while others did not. The project was viewed as helpful in increasing knowledge
      about CHD and preventive measures and encouraging healthier lifestyles. However,
      persistent barriers to change were also identified, requiring changes to the
      project that involved not only matching intervention materials and messages to
      observable, superficial characteristics of the target population, but more
      fundamental changes that address the cultural, social, historical, environmental
      and psychological forces that influence health behaviour. CONCLUSION: CHD
      prevention initiatives need to identify and respond to deep-rooted influences on
      health-behaviour in 'at-risk' groups, in addition to superficial characteristics
      of the target populations. It is important for specific prevention initiatives to
      be linked into wider CHD frameworks to ensure transferability of learning and
      integration within wider service provision.

PMID- 17224166
TI  - Dexmedetomidine-induced pulmonary alterations in sheep.
AB  - Alpha(2) agonist-induced pulmonary oedema in sheep might be related to
      alterations in pulmonary haemodynamics and/or activation of inflammatory
      processes. In seven sevoflurane-anaesthetized sheep pulmonary haemodynamics,
      arterial oxygen tensions, nitric oxide and prostaglandin E(2) concentrations were
      determined before and after intravenous dexmedetomidine (2microg kg(-1)). In a
      second trial, lung tissue was sampled for histopathology and quantitative real
      time PCR for IL-1beta and iNOS mRNA in a control sheep and 2, 10 and 30min after
      dexmedetomidine. Computer tomography of the lung under sevoflurane anaesthesia
      before and after dexmedetomidine was performed. Two minutes after dexmedetomidine
      mean pulmonary artery pressure, pulmonary arterial occlusion pressure and
      estimated capillary pressurewere significantly increased to 34.5mmHg, 22.2mmHg
      and 27.1mmHg, respectively. On computer tomography, lung density increased
      immediately after dexmedetomidine, with maximal density occurring between 9 and
      12min. Histopathology was consistent with vascular congestion followed by protein
      and erythrocyte extravasation into alveoli. Increased iNOS mRNA levels were
      detected in sevoflurane anaesthetized animals only. An IL-1beta signal occurred
      after morphological changes had occurred in lung tissue. These findings support
      hydrostatic stress as the underlying cause of alpha(2) agonist-induced pulmonary
      oedema in sheep.

PMID- 17224167
TI  - Insecticidal plant cyclotides and related cystine knot toxins.
AB  - Cyclotides are small disulphide-rich peptides found in plants from the violet
      (Violaceae), coffee (Rubiaceae) and cucurbit (Cucurbitaceae) families. They have
      the distinguishing structural features of a macrocyclic peptide backbone and a
      cystine knot made up of six conserved cysteine residues, which makes cyclotides
      exceptionally stable. Individual plants express a suite of cyclotides in a wide
      range of tissue types, including leaves, flowers, stems and roots and it is
      thought that their natural function in plants is as defence agents. This proposal
      is supported by their high expression levels in plants and their toxic and growth
      retardant activity in feeding trials against Helicoverpa spp. insect pests. This
      review describes the structures and activities of cyclotides with specific
      reference to their insecticidal activity and compares them with structurally
      similar cystine knot proteins from peas (Pisum sativum) and an amaranthus crop
      plant (Amaranthus hypocondriancus). More broadly, cystine knot proteins are
      common in a wide range of organisms from fungi to mammals, and it appears that
      this interesting structural motif has evolved independently in different
      organisms as a stable protein framework that has a variety of biological
      functions.

PMID- 17224169
TI  - Disinfection of Legionella pneumophila by photocatalytic oxidation.
AB  - Photocatalytic oxidation (PCO) was proven to be efficacious in the inactivation
      of Legionella pneumophila serogroup 1 Strains 977, 1009, 1014 and ATCC 33153. The
      local (Strains 997, 1009 and 1014) and ATCC (Strain 33153) strains showed
      sensitivity differences towards PCO. The inactivation mechanisms of PCO were
      investigated by transmission and scanning electron microscopy by which PCO was
      found to disintegrate the cells eventually. Before the disintegration, there was
      lipid peroxidation of outer and cytoplasmic membrane causing holes formation and
      leading to the entry of OH into the cells to oxidize the intracellular
      components. Fatty acid profile analysis found that the amount of saturated, 16
      carbon branched-chain fatty acid, which is predominant in Legionella, decreased
      in the surviving populations from PCO. A relationship between the amount of this
      fatty acid and the PCO sensitivity of the tested strains was also observed.
      Mineralization of cells by PCO was proven by total organic carbon analysis.

PMID- 17224168
TI  - Sea anemone venom as a source of insecticidal peptides acting on voltage-gated
      Na+ channels.
AB  - Sea anemones produce a myriad of toxic peptides and proteins of which a large
      group acts on voltage-gated Na+ channels. However, in comparison to other
      organisms, their venoms and toxins are poorly studied. Most of the known voltage
      gated Na+ channel toxins isolated from sea anemone venoms act on neurotoxin
      receptor site 3 and inhibit the inactivation of these channels. Furthermore, it
      seems that most of these toxins have a distinct preference for crustaceans. Given
      the close evolutionary relationship between crustaceans and insects, it is not
      surprising that sea anemone toxins also profoundly affect insect voltage-gated
      Na+ channels, which constitutes the scope of this review. For this reason, these
      peptides can be considered as insecticidal lead compounds in the development of
      insecticides.

PMID- 17224170
TI  - Treatment of leachate from MSWI bottom ash landfilling with anaerobic sulphate
      reducing process.
AB  - Removal of sulphate and toxic elements from the leachate of a field landfill
      lysimeter (112m(3)), containing municipal solid waste incineration (MSWI) bottom
      ash, was studied. The leachate was treated in two parallel laboratory upflow
      anaerobic sludge blanket (UASB) reactors without and with ethanol as additional
      carbon source. With ethanol more than 65% of sulphate was removed, while without
      ethanol removal was negligible. The treatment removed Ba, Ca, Cu, Mn, Mo, Ni, Pb,
      Tl, Sb, Se, Sr, and Zn of the studied 35 trace and other elements. The sequential
      extraction of the reactor sludge at the end of runs confirmed that with a few
      exceptions (Ba, Ca, and Cu) the main mechanism by which the elements were removed
      was precipitation as sulphides.

PMID- 17224171
TI  - Fermentation and elutriation of primary sludge: effect of SRT on process
      performance.
AB  - A primary sludge fermentation-elutriation pilot plant was operated using in-line
      and side-stream schemes. The influence of solids retention time, recirculation
      sludge flow-rate and solids concentration on the fermentation-elutriation process
      performance has been assessed in this paper. The use of high elutriation flows
      (12% of influent flow) improved the volatile fatty acids (VFA) concentration in
      the effluent stream. Suspended solids removal efficiency decreased in the primary
      settler when the solids retention time (SRT) was increased from 4 to 8 days.
      Disintegration step during hydrolysis process was pointed out as the main reason
      for that decrease. Maximum VFA productions were achieved at SRT between 6 and 8
      days at the highest elutriation flow tested for both configurations. Propionic,
      butyric and valeric volatile fatty acids percentage increased when total solids
      sludge concentrations above 23,000mgl(-1) were used. Hydrogen accumulation,
      causing acetogenic bacteria inhibition, was indicated as the reason for C(3)-C(5)
      fatty acids accumulation.

PMID- 17224172
TI  - Oxygen diffusion in active layer of aerobic granule with step change in
      surrounding oxygen levels.
AB  - High biomass density and large size limit the transfer of dissolved oxygen (DO)
      in aerobic granules. In the literature, the oxygen diffusivity is often employed
      as an input parameter for modeling transport processes in aerobic granules. The
      interior of an aerobic granule was observed to be highly heterogeneous. In this
      work, the distributions of extracellular polymeric substances (EPS) and cells in
      the interior of phenol-fed and acetate-fed granules were built up using a five
      fold staining scheme, combined with the use of a confocal laser scanning
      microscope (CLSM). The steady-state and transient DO with step changes in
      surrounding DO levels at various depths were measured in the granules using
      microelectrodes. Cells were probed in a surface layer of thickness 125-375
      microm. A marked fall in DO was also noted over this surface layer. No aerobic
      oxidation could occur beneath the active layer, indicating the oxygen transfer
      limit. Fitting the steady-state and transient DO data over the active surface
      layer yielded apparent diffusivities of oxygen were (9.5+/-3.5)x10(-10)m(2)s(-1)
      for the phenol-fed granule and (3.5+/-1.0)x10(-10)m(2)s(-1) for the phenol-fed
      granule. These values were lower than those adopted in models in the literature.

PMID- 17224173
TI  - Effect of free ammonia on the respiration and growth processes of an enriched
      Nitrobacter culture.
AB  - The inhibitory effect of free ammonia (FA;NH(3)) on the metabolism of Nitrobacter
      is investigated using a method that allows decoupling energy generation from
      growth processes. A lab-scale sequencing batch reactor (SBR) was operated for the
      enrichment of Nitrobacter. Fluorescent in situ hybridization (FISH) analysis
      showed that 73% of the bacterial population in the reactor was Nitrobacter, while
      no Nitrospira was detected. Batch tests were carried out to measure the oxygen
      uptake rate (OUR) by the culture at various FA levels, in the presence (OUR with
      CO(2)) or absence (OUR without CO(2)) of inorganic carbon (CO(2), HCO(3)(-) and
      CO(3)(2-)). The FA inhibition on the respiration initiated at below 1mgNH(3)-NL(
      1) in both cases. OUR without CO(2) gradually decreased by 12% when the FA
      concentration increased from 0 to approximately 4mgNH(3)-NL(-1) and remained at
      the same level till an FA level of 9mgNH(3)-NL(-1) (the highest FA concentration
      applied in this study). This indicates that FA has a limited inhibitory effect on
      the respiratory capability of Nitrobacter. Starting from a level that is 15%
      higher than OUR without CO(2) when no FA was present, OUR with CO(2)decreased
      more rapidly than OUR without CO(2) reaching the same level as OUR without CO(2)
      when FA was between 6-9mgNH(3)-NL(-1). This implies that in this range of FA the
      presence of inorganic carbon did not cause any increase in the respiration
      activity of Nitrobacter. The results suggest that, while still oxidizing nitrite
      at approximately 75% of the non-inhibited rate, Nitrobacter likely ceased to grow
      at an FA level of above 6mgNH(3)-NL(-1). While the real mechanisms remain to be
      identified, this study indicates that the FA inhibition on Nitrobacter is likely
      much more serious than suggested by previous studies where OUR with CO(2) (or the
      equivalent nitrite oxidation rate) was used as the sole measure of the inhibitory
      effects.

PMID- 17224174
TI  - Regeneration of granular activated carbon with adsorbed trichloroethylene using
      wet peroxide oxidation.
AB  - The objective of this study is to clarify the regeneration of granular activated
      carbon (GAC) adsorbed trichloroethylene (TCE) using wet peroxide oxidation (WPO).
      TCE and TOC concentrations decreased during WPO, whereas Cl(-) accumulated in
      water indicating that TCE was not only decomposed but was also mineralized to Cl(
      ) and CO(2) using WPO. Regeneration efficiencies (q/q(0)) of GAC regenerated at
      150, 165 and 180 degrees C (initial pH 4) were 0.36, 0.45, 0.48, respectively. In
      addition, regeneration efficiencies of GAC regenerated in the solution of various
      initial pH (2.5, 3.0, 4.0) at 180 degrees C were 0.71, 0.60, 0.48, respectively.
      These results suggest that regeneration of GAC is more effective at higher
      reaction temperature and lower initial pH of the solution. In the repeated
      regeneration of GAC, the adsorption capacity of GAC for TCE gradually decreased
      and regeneration efficiency of the regenerated GAC at sixth step was 0.40. The
      adsorption capacity loss of regenerated GAC is probably due to oxidation of GAC
      during WPO.

PMID- 17224175
TI  - On the translation of uncertainty from toxicokinetic to toxicodynamic models--the
      TCDD example.
AB  - When estimating human health risks from exposure to TCDD using toxicokinetic and
      toxicodynamic models, it is important to understand how model choice and
      assumptions necessary for modeling add to the uncertainty of risk estimates.
      Several toxicokinetic models have been proposed for the risk assessment of
      dioxins, in particular the elimination kinetics in humans has been a matter of
      constant debate. For a long time, a simple linear elimination kinetics has been
      common choice. Thus, it was used for the statistical analysis of the largest
      occupationally exposed cohort, the German Boehringer cohort. We challenge this
      assumption by considering, amongst others, a nonlinear modified Michaelis-Menten
      type elimination kinetics, the so-called Carrier kinetics. Using the area under
      the lipid TCDD concentration time curve as dose metrics, we model the time to
      cancer-related death using the Cox proportional hazards model as toxicodynamic
      model. This risk assessment set-up was simulated in order to quantify uncertainty
      of both the dose (TCDD body burden) and the risk estimates, depending on the use
      of the kinetic model, variations of carcinogenic effect of TCDD and variations of
      latency period (lag time). If past exposure is estimated assuming a linear
      elimination kinetics although a Carrier kinetics actually holds, then high
      exposures in reality will be underestimated through statistical analysis and low
      exposures will be overestimated, respectively. This bias will carry over on the
      estimated individual concentration-time curves and the therefrom derived TCDD
      dose metric values. Using biased dose values when estimating a dose-response
      relationship will finally lead to biased risk estimates. The extent of bias and
      the decrease of precision are quantified in selected scenarios through this
      simulation approach. Our findings are in concordance with recent results in the
      field of dioxin risk assessment. They also reinforce the general demand for the
      scheduled uncertainty assessments in risk analyses.

PMID- 17224177
TI  - Effects of aerobic exercise training on antioxidant enzyme activities and mRNA
      levels in soleus muscle from young and aged rats.
AB  - The aim of this study was to investigate the effect of aerobic exercise training
      on activities and mRNA levels of catalase (CAT), glutathione peroxidase (GPX),
      Cu,Zn- and Mn-superoxide dismutases (SOD), TBARS content, and xanthine oxidase
      (XO) activity, in soleus muscle from young and aged rats. The antioxidant enzyme
      activities and mRNA levels were markedly increased in soleus muscle with aging.
      TBARS content of soleus muscle from the aged group was 8.3-fold higher as
      compared with that of young rats. In young rats, exercise training induced an
      increase of all antioxidant enzyme activities, except for Cu,Zn-SOD. XO also did
      not change. The TBARS content was also increased (2.9-fold) due to exercise
      training in soleus muscle from young rats. In aged rats, the activities of CAT,
      GPX and Cu,Zn-SOD in the soleus muscle did not change with the exercise training,
      whereas the activities of Mn-SOD (40%) and XO (27%) were decreased. The mRNA
      levels of Mn-SOD and CAT were decreased by 42% and 24%, respectively, in the
      trained group. Exercise training induced a significant decrease of TBARS content
      (81%) in the soleus muscle from aged rats. These findings support the proposition
      that exercise training presents an antioxidant stress effect on skeletal muscle
      from both young and aged rats.

PMID- 17224178
TI  - Growth hormone perturbations in fibromyalgia: a review.
AB  - OBJECTIVE: Fibromyalgia (FM) is a syndrome characterized by chronic widespread
      pain, fatigue, disrupted sleep, depression, and physical deconditioning. In this
      article, we review the literature on the normal activity of the hypothalamic
      pituitary-growth hormone-insulin-like growth factor-1 (HP-GH-IGF-1) axis and its
      perturbations in FM subjects. METHODS: Studies included in this review were
      accessed through an English language search of Cochrane Collaboration Reviews.
      Keyword MeSH terms included "fibromyalgia," "growth hormone" (GH), or "insulin
      like growth factor-1" (IGF-1). RESULTS: Twenty-six studies enrolling 2006
      subjects were reviewed. Overall, low levels of IGF-1 were found in a subgroup of
      subjects. Growth hormone stimulation tests often revealed a suboptimal response,
      which did not always correlate with IGF-1 levels. No consistent defects in
      pituitary function were found. Of the 3 randomized placebo controlled studies,
      only 9 months of daily injectable recombinant GH reduced FM symptoms and
      normalized IGF-1. CONCLUSIONS: These studies suggest that pituitary function is
      normal in FM and that reported changes in the HP-GH-IGF-1 axis are most likely
      hypothalamic in origin. The therapeutic efficacy of supplemental GH therapy in FM
      requires further study before any solid recommendations can be made.

PMID- 17224179
TI  - Immunohistochemical study of the reticular and vascular network of mouse lymph
      node using vibratome sections.
AB  - The function of lymph nodes is greatly influenced by their unique microanatomy,
      in which distinct subpopulations of cells are compartmentalized by a meshwork of
      reticular cells and fibres, specialized blood and lymphatic vessels and nerves.
      Using antibodies against extracellular matrix (ECM) proteins (fibronectin,
      collagen IV and laminin), proteoglycan (perlecan), and a fibroblastic marker
      (ERTR-7), the distribution and molecular organization of the system of reticular
      fibres was investigated by three-dimensional (3D) reconstruction methods.
      Fibronectin, collagen IV and laminin are restricted to reticular fibres and have
      a similar distribution pattern, whereas perlecan is limited to the vascular
      system of the lymph node. Various compartments of the lymph node, such as the B
      cell follicle, paracortex (including the high endothelial venules and
      paracortical cord), and medulla have been reconstructed to visualize their
      vasculature with respect to B and T cells. Since the morphology of lymph nodes
      may change significantly in pathological conditions, different compartments of
      reactive lymph node (after low-dose Listeria monocytogenes infection), especially
      germinal centres, were also investigated. The data presented here should
      facilitate our understanding of the 3D organization of non-immune cell components
      of lymph nodes, which is crucial for cell adhesion, migration, activation, and
      differentiation in normal and pathological conditions.

PMID- 17224176
TI  - WRN exonuclease activity is blocked by DNA termini harboring 3' obstructive
      groups.
AB  - Reactive oxygen species, generated either by cellular respiration or upon
      exposure to environmental agents such as ionizing radiation (IR), attack DNA to
      form a variety of oxidized base and sugar modifications. Accumulation of
      oxidative DNA damage has been associated with age-related disease as well as the
      aging process. Single-strand breaks harboring oxidative 3' obstructive termini,
      e.g. 3' phosphates and 3' phosphoglycolates, must be removed prior to DNA repair
      synthesis or ligation. In addition, 3' tyrosyl-linked protein damage, resulting
      from therapeutic agents such as camptothecin (CPT), must be processed to initiate
      repair. Several nucleases participate in DNA repair and the excision of 3'
      obstructive ends. As the protein defective in the segmental progeroid Werner
      syndrome (WRN) possesses 3'-5' exonuclease activity, and Werner syndrome cells
      are hypersensitive to IR and CPT, we examined for WRN exonuclease activity on 3'
      blocking lesions. Moreover, we compared side-by-side the activity of four
      prominent human 3'-5' exonucleases (WRN, APE1, TREX1, and p53) on substrates
      containing 3' phosphates, phosphoglycolates, and tyrosyl residues. Our studies
      reveal that while WRN degrades 3' hydroxyl containing substrates in a non
      processive manner, it does not excise 3' phosphate, phosphoglycolate, or tyrosyl
      groups. In addition, we found that APE1 was most active at excising 3' blocking
      termini in comparison to the disease-related exonucleases TREX1, WRN, and p53
      under identical physiological reaction conditions, and that TREX1 was the most
      powerful 3'-5' exonuclease on undamaged oligonucleotide substrates.

PMID- 17224180
TI  - HA14-1, a small molecule inhibitor of Bcl-2, bypasses chemoresistance in
      leukaemia cells.
AB  - We analyzed the biological activity of HA14-1, a small organic compound inhibitor
      of Bcl-2, against established leukaemia cell lines and blasts from acute myeloid
      leukaemia (AML) patients. HA14-1 had a potent killing activity against the
      leukaemia cell line that expressed endogenous or ectopic Bcl-2. This activity was
      mostly caspase-independent and was not altered by the expression of a multidrug
      resistant phenotype. Moreover, HA14-1 efficiently induced cell death in a broad
      spectrum of AML blasts but not in normal peripheral blood lymphocytes. Thus,
      single-agent regimens using Bcl-2 inhibitors such as HA14-1 may be advantageous
      in overcoming some forms of chemoresistance in AML.

PMID- 17224181
TI  - Poly-victimization: a neglected component in child victimization.
AB  - OBJECTIVE: To assess the role of multiple victimization, or what is termed in
      this article "poly-victimization," in explaining trauma symptomatology. METHOD:
      In a nationally representative sample of 2,030 children ages 2-17, assessment was
      made of the past year's victimization experiences and recent trauma symptoms.
      RESULTS: Children experiencing four or more different kinds of victimization in a
      single year (poly-victims) comprised 22% of the sample. Poly-victimization was
      highly predictive of trauma symptoms, and when taken into account, greatly
      reduced or eliminated the association between individual victimizations (e.g.,
      sexual abuse) and symptomatology. Poly-victims were also more symptomatic than
      children with only repeated episodes of the same kind of victimization.
      CONCLUSION: Researchers and practitioners need to assess for a broader range of
      victimizations, and avoid studies and assessments organized around a single form
      of victimization.

PMID- 17224182
TI  - Molecular cloning, sequencing and phylogenetic analysis of inflammatory cytokines
      of swamp type buffalo contrasting with other bubaline breeds.
AB  - The current research concerned in the cloning, sequencing and phylogenetic
      analysis of inflammatory cytokine (IL-1alpha, IL-1beta, IL-6 and TNF-alpha) genes
      from swamp buffalo and two bubaline breeds, CB (cross between swamp and riverine
      type buffalo) and the Bulgarian Murrah buffalo. Multiple sequence comparison
      showed a high homology between the bubaline breeds, which ranged from 99.3% to
      100.0% similarity, whereas from 98.6% to 99.0% compared to cattle. The
      phylogenetic analysis had confirmed and justified the degree of relationship
      between these bubaline species and their distinctness to each other by the
      bootstrap value (%) generated. These findings were discussed with particular
      attention to the diversity of the inflammatory cytokine proteins within closely
      related species. The result of this study concluded that a small difference in
      the cytokine structures might be the reason behind or has a contributory factor
      on the previous reports about the existence of disease resistance. However, in
      depth study is necessary to further qualify these findings.

PMID- 17224183
TI  - Evaluation of intravitreal kenalog toxicity in humans.
AB  - OBJECTIVE: To evaluate possible functional toxicity of intravitreal Kenalog
      (commercial triamcinolone acetonide) in patients' retinas. DESIGN: Observational
      case series. PARTICIPANTS: Thirty-two phakic eyes of 16 patients who had
      nonproliferative diabetic retinopathy and bilateral macular edema refractory to
      laser therapy, which had no other eye disorder and no previous ophthalmic
      operation. INTERVENTION: Kenalog (4 mg/0.1 ml) was injected intravitreally to one
      eye, whereas the second eye served as the control. The experimental eye was
      chosen as the eye with worse visual acuity (VA). MAIN OUTCOME MEASURES:
      Deterioration of electroretinogram parameters of the study eye measured at 3
      months of follow-up when compared with the electroretinogram responses of the
      fellow, control eye and when compared with electroretinogram responses obtained
      before injection. Visual acuity, intraocular pressure (IOP), and eventual
      complications were assessed. No improvement or deterioration of VA or any
      increase in IOP was regarded as a secondary outcome. RESULTS: Average maximal
      response amplitude ratios of the dark-adapted b-wave (treated/control eyes) of
      the electroretinogram were 0.93 before (P = 0.221) and 0.94 (P = 0.387) 3 months
      after Kenalog injection. Average ratios of the light-adapted b-wave amplitude
      (treated/control eyes) of the electroretinogram were 1.04 (P = 0.702) before and
      0.86 (P = 0.138) 3 months after Kenalog injection. No significant differences
      (P>0.05) were found between the electroretinogram parameters obtained from all
      eyes before and 3 months after Kenalog injection. Average VAs in the treated eyes
      were 1.08, 0.8, and 1.0 logarithm of the minimum angle of resolution units before
      and 2 and 4 months after injection, respectively. Temporary elevation of IOP was
      found in 4 treated eyes of 4 patients (25%). CONCLUSIONS: No electroretinographic
      evidence of a retinotoxic effect of intravitreal Kenalog was found in our
      patients.

PMID- 17224184
TI  - GG sequence of DNA and the human telomeric sequence react with cis-diammine
      diaquaplatinum at comparable rates.
AB  - G-quadruplex structures of telomeric sequences are of growing interest because
      they inhibit telomerase, an enzyme involved in the maintenance of telomere length
      of cancer cells. As we have shown previously, the antiparallel structure of G
      quadruplexes can be cross-linked in vitro by the anti-tumour drug cisplatin. The
      question arises whether platination of quadruplex structures of human telomeric
      sequences by cisplatin could be relevant from a biological point of view.
      Therefore, we have compared the kinetics of reactions of the diaqua form of
      cisplatin, cis-[Pt(NH(3))(2)(H(2)O)(2)](2+), with the human telomeric quadruplex
      structure, a duplex DNA and a single-stranded DNA containing one specific
      platination GG site. The ratio between the platination rate constants was
      obtained using two intramolecular competition experiments: either a construct
      with a junction between duplex DNA containing a unique GG platination site and
      the quadruplex structure of the human telomeric sequence AG(3)(T(2)AG(3))(3), or
      a construct with a junction between duplex DNA and a single strand containing
      each a unique GG platination site. Those competition experiments allowed us to
      conclude that the platination of the quadruplex is favoured over that of the GG
      duplex by a factor of about two whereas the GG duplex is platinated three times
      faster than the GG single strand.

PMID- 17224186
TI  - Self-reported data from patients with bipolar disorder: frequency of brief
      depression.
AB  - OBJECTIVE: Patients with bipolar disorder often report depressive symptoms that
      do not meet the DSM-IV criteria for an episode. Using daily self-reported mood
      ratings, we studied how changing the length requirement to that typical of
      recurrent brief depression (2-4 days) would impact the number of depressed
      episodes. METHOD: 203 patients (135 bipolar I and 68 bipolar II by DSM-IV
      criteria) recorded mood daily using ChronoRecord software on a home computer
      (30,348 total days; mean 150 days). Episodes of depression and days of depression
      outside of episodes were determined. Symptom intensity (mild versus moderate or
      severe) was investigated within and outside of depressive episodes. RESULTS:
      Decreasing the minimum duration criterion for an episode of depression to 2 days
      increased the number of patients with a depressed episode two and a half times
      (52 to 131), and quadrupled both the number of depressed episodes per patient
      (0.62 to 2.88) and the number of depressed episodes for all patients (125 to
      584). With a 2-day episode length, 34% of days of depression remained outside an
      episode. The ratio of days with severe symptoms within episodes remained
      consistent (about 25%) in spite of decreasing the episode length to 2 days.
      Considering only days with severe symptoms, about 25% remained outside of
      episodes even with a 2-day length. None of the results distinguished bipolar I
      from bipolar II disorder. LIMITATIONS: Self-reported data, computer access
      required, relatively short study length, no control group. CONCLUSION: Brief
      depressive episodes and single days of depression outside of episodes occur
      frequently in both bipolar I and bipolar II disorder. Moderate or severe symptoms
      occur during brief episodes at a ratio similar to that for episodes that meet the
      DSM-IV criteria.

PMID- 17224185
TI  - Neurocognitive impairment in middle-aged and older adults with bipolar disorder:
      comparison to schizophrenia and normal comparison subjects.
AB  - BACKGROUND: The frequency, pattern, and correlates of neurocognitive impairment
      in older patients with bipolar disorder have received little study. We examined
      neurocognitive abilities in middle-aged and older adults with bipolar disorder to
      groups with schizophrenia or normal subjects, as well as the relation of
      neurocognition to clinical characteristics. METHOD: We administered a battery of
      neurocognitive and clinical measures to older (45-85 years) outpatients with
      bipolar disorder (n=67), schizophrenia (n=150), and normal comparison subjects
      (n=85). Within the bipolar group, we assessed the association between
      neurocognitive performance and psychiatric symptoms, quality of life, and
      medication status. RESULTS: The group with bipolar disorder differed on nearly
      all neuropsychological tests compared to normal subjects, with medium effect
      sizes. Bipolar patients as impaired as those with schizophrenia on half of the
      tests administered, and performed better on the remaining tests, with small
      effect sizes. Neurocognitive deficits in bipolar disorder group related to lower
      quality of life, but not to psychiatric symptom severity or duration of illness.
      LIMITATIONS: Samples were outpatients with mild-moderate symptoms, and findings
      may not generalize to acutely ill populations. We lacked data on illness history
      to examine the cumulative impact of psychopathology. CONCLUSIONS: Among
      clinically stable middle-aged and older outpatients, bipolar disorder was
      associated with substantial neurocognitive impairment, with a pattern that was
      somewhat distinct from that found in schizophrenia. Deficits in the bipolar group
      were not related to severity or duration of psychiatric symptoms, but were
      related to quality of life. Bipolar disorder often involve disabling and enduring
      cognitive impairments in older outpatients.

PMID- 17224187
TI  - The historical roots of the "bipolar spectrum": did Aristotle anticipate
      Kraepelin's broad concept of manic-depression?
AB  - The construct of bipolar disorder, or bipolar spectrum disorders, has been a
      source of controversy in recent years. Some have argued that subtle variants
      within the putative bipolar spectrum are merely the creation of overzealous
      clinicians, perhaps encouraged by various special interest groups. In reality,
      the concept of a bipolar spectrum may be inferred from numerous classical
      sources, dating back to the 19th century and even into antiquity. The Greek
      philosopher Aristotle, usually considered the author of a work called Problemata,
      appears to have recognized some form of the bipolar spectrum, more than two
      millennia ago. This recognition continues throughout the 19th century, and into
      our own time. Such transcultural findings across many centuries have implications
      for the "objective" nature of psychiatric disease.

PMID- 17224188
TI  - Use of FoxP3 expression to identify regulatory T cells in healthy dogs and dogs
      with cancer.
AB  - Regulatory T cells (Treg) are a distinct group of T lymphocytes with
      immunosuppressive properties that serve normally to prevent harmful autoimmune
      responses. However, Tregs can also interfere with beneficial immune responses
      such as anti-tumor and anti-viral immunity in humans and rodents. Given the
      overall importance of Tregs, it is likely that they play an important role in
      diseases of dogs as well. However, at present reagents required for
      identification of Tregs in dogs are not available. Therefore, we investigated
      whether expression of FoxP3, a transcription factor that is highly expressed in
      Tregs in humans and rodents could also be used to identify Tregs in dogs. We
      found that a cross-reactive FoxP3 antibody identified a subset of CD4(+) T cells
      in blood and lymph nodes of dogs. By flow cytometry the mean percentage of
      FoxP3(+)CD4(+) T cells in normal dogs was 4.3% in blood and 9.8% in the lymph
      nodes. In dogs with cancer, there was a significant increase in numbers of Treg
      in blood (7.5%) and tumor-draining lymph nodes (17.1%) compared to age-matched
      healthy control dogs. We also found that FoxP3(+)CD4(+) T cells in dogs could be
      significantly expanded in vitro by TCR activation together with addition of TGF
      beta and IL-2. Treated cells also significantly increased expression of TGF-beta
      and IL-10mRNA. We conclude from these studies that a cross-reactive FoxP3
      antibody can be used to identify Tregs in dogs and that this reagent may serve as
      a useful tool for investigating the role of Treg in a variety of diseases of
      dogs.

PMID- 17224190
TI  - The heterodox nature of "Turban Pins" in foreign body aspiration; the central
      anatolian experience.
AB  - OBJECTIVE: The aim of this study is to determine the age and sex distribution and
      the nature of aspirated foreign bodies (FBs). We also compared Turban Pins (TP)
      with other FBs and discussed the extracting techniques. METHODS: From 1987
      through 2006, 414 patients were managed and the records of the patients were
      retrospectively reviewed. RESULTS: Girls (56%) were influenced much more than the
      boys (44%). The median age was 4, however median age for girls and boys were 11
      and 2, respectively. The 50% of the foreign body aspiration (FBA) were observed
      in the first years of life. There was also a great tendency to occur in the
      adolescent age group (32%), especially for girls. The most commonly aspirated
      foreign body was Turban pin (TP) (n=121) among 332 foreign bodies. FBs were
      successfully removed by rigid bronchoscopy in 94% of the patients. In patients
      who had a negative history (n=49), bronchoscopy was performed according to
      clinical suspicion, and it revealed foreign bodies in 41%. Thoracotomy was
      performed in eight (2.4%) patients. We had no mortality. CONCLUSIONS: These cases
      showed us that the type and age groups of FBA varies according to cultural
      conditions. We found that TP aspiration has different characteristics and it
      deserves a special attention. Suspicion is an important indication for
      bronchoscopy. We prefer rigid bronchoscopy because success rate is satisfactory.

PMID- 17224191
TI  - Spatiotemporal representations in the olfactory system.
AB  - A complete understanding of the mechanisms underlying any kind of sensory, motor
      or cognitive task requires analysis from the systems to the cellular level. In
      olfaction, new behavioural evidence in rodents has provided temporal limits on
      neural processing times that correspond to less than 150ms--the timescale of a
      single sniff. Recent in vivo data from the olfactory bulb indicate that, within
      each sniff, odour representation is not only spatially organized, but also
      temporally structured by odour-specific patterns of onset latencies. Thus, we
      propose that the spatial representation of odour is not a static one, but rather
      evolves across a sniff, whereby for difficult discriminations of similar odours,
      it is necessary for the olfactory system to "wait" for later-activated
      components. Based on such evidence, we have devised a working model to assess
      further the relevance of such spatiotemporal processes in odour representation.

PMID- 17224189
TI  - Dendritic cell-T cell interactions: CD8 alpha alpha expressed on dendritic cells
      regulates T cell proliferation.
AB  - Expression of the CD8 alpha alpha homodimer has been used to differentiate
      lymphoid (CD8alpha(+)) from myeloid (CD8alpha(-)) dendritic cells (DCs). We have
      reported that CD8alpha(+) and CD8alpha(-) DCs have differential abilities to
      stimulate proliferation in allogeneic T cells. However, no specific function has
      been attributed to DC-derived CD8alpha. The current study examines the hypothesis
      that CD8 alpha alpha expression on DCs regulates DC-induced T cell activation.
      CD8alpha(-) transduced bone marrow-derived DCs were more potent stimulators of T
      cell proliferation, and produced significantly greater quantities of IL-12 in co
      culture with T cells. LCK, a kinase whose expression is reported to be T cell
      restricted and known to bind to the cytoplasmic tail of CD8 alpha beta in T
      cells, was detected readily in primary CD8alpha(+) splenic DCs and at greater
      levels than CD8alpha(-) DCs from the same tissues. LCK also co-precipitated with
      CD8alpha on immunblots strongly suggesting its role in CD8alpha(+) DC-induced T
      cell activation. Collectively, these data show that CD8alpha expressed on DC may
      not only be a lineage/maturation marker but also contribute to DC function.

PMID- 17224192
TI  - Arrhythmia and reduced heart rate variability during pregnancy in women with
      congenital heart disease and previous reparative surgery.
AB  - OBJECTIVES: Tachyarrhythmia during pregnancy may have an adverse effect on the
      mother and the fetus. Heart rate variability (HRV) is a significant marker of
      autonomic nervous function and may predict tachyarrhythmia. HRV and incidence of
      arrhythmia in women with repaired congenital heart disease (CHD) during pregnancy
      were examined. METHODS: Twenty-eight patients with repaired CHD (35 pregnancies,
      age: 26+/-3.5 years at their first pregnancy, 22+/-6.2 years post-repair) and 19
      healthy pregnant volunteers (controls, 19 pregnancies, age: 28+/-5.5 years) were
      enrolled. Holter monitoring and laboratory tests were examined at 28+/-4 weeks of
      gestation and 22+/-13 weeks postpartum in patients and 28+/-3 weeks of gestation
      in controls. Time and frequency variables of HRV were analyzed. RESULTS: Compared
      with controls and postpartum, there was a significantly higher incidence of
      tachyarrhythmia during pregnancy in women with CHD (4 episodes of
      supraventricular tachyarrhythmia (SVT) and 5 of non-sustained ventricular
      tachycardia, P=0.02). HR response in tetralogy of Fallot was impaired (781+/-50
      ms, P=0.02). Most of HRV variables were significantly suppressed (average RR
      740+/-64 ms, SDRR 99+/-22 ms, low and high frequency domains (341+/-165 ms2 and
      256+/-181 ms2) (P<0.05). Reduced SDRR and high frequency domains were observed in
      patients with tachyarrhythmia. Furthermore, there were increased left ventricular
      end-diastolic dimensions 48+/-5 mm (P=0.001) and atrial natriuretic peptide
      levels 33+/-13 pg/ml (P=0.01) in the CHD patients compared with postpartum
      levels. CONCLUSIONS: Impaired autonomic nervous activity, volume overload of the
      heart and operative scar all play a contributory role in higher incidence of
      tachyarrhythmia during pregnancy in patients with repaired CHD compared to
      healthy pregnant controls. Close monitoring of patients with CHD for
      tachyarrhythmia during pregnancy is, thus, warranted.

PMID- 17224193
TI  - Demonstrating freedom from disease using multiple complex data sources 1: a new
      methodology based on scenario trees.
AB  - Current methods to demonstrate zone or country freedom from disease are based on
      either quantitative analysis of the results of structured representative surveys,
      or qualitative assessments of multiple sources of evidence (including complex non
      representative sources). This paper presents a methodology for objective
      quantitative analysis of multiple complex data sources to support claims of
      freedom from disease. Stochastic scenario tree models are used to describe each
      component of a surveillance system (SSC), and used to estimate the sensitivity of
      each SSC. The process of building and analysing the models is described, as well
      as techniques to take into account any lack of independence between units at
      different levels within a SSC. The combination of sensitivity estimates from
      multiple SSCs into a single estimate for the entire surveillance system is also
      considered, again taking into account lack of independence between components. A
      sensitivity ratio is used to compare different components of a surveillance
      system. Finally, calculation of the probability of country freedom from the
      estimated sensitivity of the surveillance system is illustrated, incorporating
      the use and valuation of historical surveillance evidence.

PMID- 17224194
TI  - A virtual reality solution for evaluation of radiotherapy plans.
AB  - This report presents a VR system for evaluation of treatment plans used in
      radiotherapy (RT), developed to improve the understanding of the spatial
      relationships between the patient anatomy and the calculated dose distribution.
      The VR system offers visualization through interactive volume rendering of RT
      dose distribution and computed tomography (CT) and surface and line rendering of
      RT structures such as target volumes and organs at risk. The VR system has been
      installed and networked in a hospital room used for the daily RT conferences,
      making stereoscopic viewing of treatment planning data for clinical cases
      possible.

PMID- 17224195
TI  - Randomised trial of standard 2D radiotherapy (RT) versus intensity modulated
      radiotherapy (IMRT) in patients prescribed breast radiotherapy.
AB  - BACKGROUND: Radiation dose distributions created by two dimensional (2D)
      treatment planning are responsible for partial volumes receiving >107% of the
      prescribed dose in a proportion of patients prescribed whole breast radiotherapy
      after tumour excision of early breast cancer. These may contribute to clinically
      significant late radiation adverse effects. AIM: To test three dimensional (3D)
      intensity modulated radiotherapy (IMRT) against 2D dosimetry using standard wedge
      compensators in terms of late adverse effects after whole breast radiotherapy.
      METHODS: Three hundred and six women prescribed whole breast radiotherapy after
      tumour excision for early stage cancer were randomised to 3D IMRT (test arm) or
      2D radiotherapy delivered using standard wedge compensators (control arm). All
      patients were treated with 6 or 10MV photons to a dose of 50Gy in 25 fractions to
      100% in 5 weeks followed by an electron boost to the tumour bed of 11.1Gy in 5
      fractions to 100%. The primary endpoint was change in breast appearance scored
      from serial photographs taken before radiotherapy and at 1, 2 and 5 years follow
      up. Secondary endpoints included patient self-assessments of breast discomfort,
      breast hardness, quality of life and physician assessments of breast induration.
      Analysis was by intention to treat. RESULTS: 240 (79%) patients with 5-year
      photographs were available for analysis. Change in breast appearance was
      identified in 71/122 (58%) allocated standard 2D treatment compared to only
      47/118 (40%) patients allocated 3D IMRT. The control arm patients were 1.7 times
      more likely to have a change in breast appearance than the IMRT arm patients
      after adjustment for year of photographic assessment (95% confidence interval 1.2
      2.5, p=0.008). Significantly fewer patients in the 3D IMRT group developed
      palpable induration assessed clinically in the centre of the breast, pectoral
      fold, infra-mammary fold and at the boost site. No significant differences
      between treatment groups were found in patient reported breast discomfort, breast
      hardness or quality of life. CONCLUSION: This analysis suggests that minimisation
      of unwanted radiation dose inhomogeneity in the breast reduces late adverse
      effects. Incidence of change in breast appearance was statistically significantly
      higher in patients in the standard 2D treatment arm compared with the IMRT arm. A
      beneficial effect on quality of life remains to be demonstrated.

PMID- 17224196
TI  - Friedrich Dessauer's (1881-1963) contributions to the development of radiotherapy
      in Turkey.
AB  - Famous physicist Friedrich Dessauer carried out innovative studies in the field
      of radiotherapy in Turkey where he took refuge escaping from the political
      situation in Germany before the Second World War. The paper deals with Dessauer's
      works for the establishment of a radiotherapy institute in Turkey and his
      contributions to this field.

PMID- 17224197
TI  - Early clinical and radiological pulmonary complications following breast cancer
      radiation therapy: NTCP fit with four different models.
AB  - OBJECTIVE: To fit four different NTCP (Normal Tissue Complication Probability)
      models to prospectively collected data on short-term pulmonary complications
      following breast cancer radiotherapy (RT). MATERIALS/METHODS: Four hundred and
      seventy-five breast cancer patients, referred to the Radiotherapy Department at
      Stockholm Soder Hospital (1994-1998) for adjuvant post-operative RT were
      prospectively followed for pulmonary complications 1, 4 and 7 months after the
      completion of RT. Eighty-seven patients with complete dose-volume histogram (DVH)
      of the ipsilateral lung were selected for the present analysis. Mean dose to the
      ipsilateral lateral lung ranged from 2.5 to 18Gy (median 12Gy). Three different
      endpoints were considered: (1) clinical pneumonitis scored according to CTC-NCIC
      criteria: asymptomatic (grade 0) vs grade 1 and grade 2; (2) radiological changes
      assessed with diagnostic chest X-ray: no/slight radiological changes vs
      moderate/severe; (3) radiological changes assessed with CT: no/slight vs
      moderate/severe. Four NTCP models were used: the Lyman model with DVH reduced to
      the equivalent uniform dose (LEUD), the Logit model with DVH reduced to EUD, the
      Mean Lung Dose (MLD) model and the Relative Seriality (RS) model. The data
      fitting procedure was done using the maximum likelihood analysis. The analysis
      was done on the entire population (n=87) and on a subgroup of patients treated
      with loco-regional RT (n=44). RESULTS: 24/87 patients (28%) developed clinical
      pneumonitis; 28/81 patients (35%) had radiological side effects on chest X-rays
      and 11/75 patients (15%) showed radiological density changes on Computed
      Tomography (CT). The analysis showed that the risk of clinical pneumonitis was a
      smooth function of EUD (calculated from DVH using n=0.86+/-0.10, best fit
      result). With LEUD, the relationship between EUD and NTCP could be described with
      a D(50) of 16.4Gy+/-1.1Gy and a steepness parameter m of 0.36+/-0.7. The results
      found in the overall population were substantially confirmed in the subgroup of
      patients treated with loco-regional RT. CONCLUSIONS: A large group of prospective
      patient data (87 pts), including grade 1 pneumonitis, were analysed. The four
      NTCP models fit quite accurately the considered endpoints. EUD or the mean lung
      dose are robust and simple parameters correlated with the risk of pneumonitis.
      For all endpoints the D(50) values ranged in an interval between 10 and 20Gy.

PMID- 17224198
TI  - Incentive value, unclear task difficulty, and cardiovascular reactivity in active
      coping.
AB  - An experiment with 44 participants assessed the moderating effects of four levels
      of incentive value on cardiovascular responses in active coping. Randomly
      assigned to one of four different incentive conditions, participants performed a
      memory task without knowing its difficulty in advance. By means of successfully
      performing the task participants could either win no reward, 10 Swiss Francs, 20
      Swiss Francs, or 30 Swiss Francs. In accordance with the theoretical predictions
      derived from motivational intensity theory, reactivity of systolic blood pressure
      and heart rate monotonically increased with incentive value. Thereby, these
      findings provide additional empirical evidence for the predictions of
      motivational intensity theory with regard to unclear task difficulty and extend
      recent research (Richter, M., Gendolla, G.H.E., 2006. Incentive effects on
      cardiovascular reactivity in active coping with unclear task difficulty. Int. J.
      Psychophysiol. 61, 216-225.), which was not conclusive regarding the predicted
      monotonic relationship between incentive value and cardiovascular reactivity
      under conditions of unclear task difficulty.

PMID- 17224199
TI  - Serine scanning: a tool to prove the consequences of N-glycosylation of proteins.
AB  - N-Glycosylation of proteins is a common posttranslational modification in
      eukaryotes. Often this results in enhanced protein stability through protection
      by the attached sugar moieties. Due to its 13 potential N-glycosylation motifs (N
      X-T/S), recombinant hydroxynitrile lyase isoenzyme 5 from almonds (PaHNL5) is
      secreted by the heterologous host Pichia pastoris in a massively glycosylated
      form, and it shows extraordinary stability at low pH. The importance of N
      glycosylation in general, and individual glycosylation sites in particular for
      stability at low pH were investigated. To identify especially important
      glycosylation sites asparagine from all N-X-S/T-motifs was replaced by serine.
      Thus, critical sites, which contributed to overall enzyme activity and/or
      stability, were identified individually. One glycosylation site revealed to be
      essential for stability at low pH. After enzymatic deglycosylation, leaving only
      one acetylglucosamine attached to asparagines, PaHNL5 retained most of its
      stability at low pH. Protonation effects in the active site as well as higher
      order aggregational events upon incubation in low pH were excluded. This study
      provides evidence for the interconnection of N-glycosylation and stability at low
      pH for PaHNL5. Moreover, serine scanning was proven to be applicable for quick
      identification of critical glycosylation sites.

PMID- 17224201
TI  - Identification and characterization of the novel gene GhDBP2 encoding a DRE
      binding protein from cotton (Gossypium hirsutum).
AB  - A cDNA encoding one novel DRE-binding protein, GhDBP2, was isolated from cotton
      seedlings. It is classified into the A-6 group of DREB subfamily based on
      multiple sequence alignment and phylogenetic characterization. Using semi
      quantitative RT-PCR, we found that the GhDBP2 transcripts were greatly induced by
      drought, NaCl, low temperature and ABA treatments in cotton cotyledons. The DNA
      binding properties of GhDBP2 were analyzed by electrophoretic mobility shift
      assay (EMSA), showing that GhDBP2 successfully binds to the previously
      characterized DRE cis-element as well as the promoter region of the LEA D113
      gene. Consistent with its role as a DNA-binding protein, GhDBP2 is preferentially
      localized to the nucleus of onion epidermal cells. In addition, when GhDBP2 is
      transiently expressed in tobacco cells, it activates reporter gene expression
      driven by the LEA D113 promoter. Taken together, our results indicate that GhDBP2
      is a DRE-binding transcriptional activator involved in activation of down-stream
      genes such as LEA D113 expression through interaction with the DRE element, in
      response to environmental stresses as well as ABA treatment.

PMID- 17224200
TI  - P60-c-src suppresses apoptosis through inhibition of caspase 8 activation in
      hepatoma cells, but not in primary hepatocytes.
AB  - BACKGROUND/AIMS: Failure to induce apoptosis triggered by members of the death
      receptor family has been described in hepatocellular carcinoma (HCC) and
      sensitization of malignant cells to pro-apoptotic molecules such as TRAIL has
      been proposed as an alternative cancer therapy. Limiting to this approach are the
      resistance of many tumor cells to TRAIL and safety concerns about the toxicity of
      TRAIL in normal hepatocytes. METHODS: We here explored the possibility that the
      protooncogene c-Src, known to be overexpressed in a variety of tumors, could be
      specifically responsible for the loss of response to receptor-mediated apoptosis.
      RESULTS: Cotreatment of several hepatoma cell lines with the Src inhibitor PP2
      potently sensitized these cells to TRAIL and CD95, dramatically decreasing
      effective doses of TRAIL to as low as 1 ng/ml. Remarkably, Src-inhibition did not
      synergize with TRAIL signaling in primary hepatocytes. Specific siRNAs showed
      that the effect was due to blockade of p60(c-Src) and occurred through increased
      recruitment of caspase 8. CONCLUSIONS: We provide evidence that p60(c-Src) is an
      important and effective suppressor of receptor-mediated apoptosis in hepatoma
      cells but not in primary human hepatocytes. Inhibition of Src sensitizes tumor
      cells to apoptosis and decreases effective doses of TRAIL to therapeutic
      concentrations.

PMID- 17224202
TI  - A low glycaemic index breakfast cereal preferentially prevents children's
      cognitive performance from declining throughout the morning.
AB  - This study investigated whether the glycaemic index (GI) of breakfast cereal
      differentially affects children's attention and memory. Using a balanced cross
      over design, on two consecutive mornings 64 children aged 6-11 years were given a
      high GI cereal and a low GI cereal in a counterbalanced order. They performed a
      series of computerised tests of attention and memory, once prior to breakfast and
      three times following breakfast at hourly intervals. The results indicate that
      children's performance declines throughout the morning and that this decline can
      be significantly reduced following the intake of a low GI cereal as compared with
      a high GI cereal on measures of accuracy of attention (M=-6.742 and -13.510,
      respectively, p<0.05) and secondary memory (M=-30.675 and -47.183, respectively,
      p<0.05).

PMID- 17224203
TI  - Time series analysis of variables associated with daily mean emergency department
      length of stay.
AB  - STUDY OBJECTIVE: We measure the effect of various input, throughput, and output
      factors on daily emergency department (ED) mean length of stay per patient (daily
      mean length of stay). METHODS: The study was a retrospective review of 93,274 ED
      visits between April 15, 2002, and December 31, 2003. The association between the
      daily mean length of stay and the independent variables was assessed with
      autoregressive moving average time series analysis (ARIMA). The following
      independent variables were measured per 24-hour period: number of elective
      surgical admissions, ED volume, number of ED admissions, number of ED ICU
      admissions, number of ED clinical attending hours, hospital medical-surgical
      occupancy (hospital occupancy), and day of the week. RESULTS: Three factors were
      independently associated with daily mean length of stay in time series analysis:
      number of elective surgical admissions, number of ED admissions, and hospital
      occupancy. The daily mean length of stay increased by 0.21 minutes for every
      additional elective surgical admission, 2.2 minutes for every additional
      admission, and 4.1 minutes for every 5% increase in hospital occupancy. Elective
      surgical admissions were associated with a maximum of 35 hours of additional ED
      dwell time. The model accounted for 31.5% of the variability in daily mean length
      of stay. The final model parameters for the ARIMA analysis were autoregressive
      term (1) moving average (1). CONCLUSION: Hospital occupancy and the number of ED
      admissions are associated with daily mean length of stay. Every additional
      elective surgical admission prolonged the daily mean length of stay by 0.21
      minutes per ED patient. Autocorrelation exists between the daily mean length of
      stay of the current day and the previous day.

PMID- 17224204
TI  - Synthesis and antigenotoxic activity of some naphtho[2,1-b]pyrano[3,2
      e][1,2,4]triazolo[1,5-c]pyrimidine derivatives.
AB  - In this study, some pyranotriazolopyrimidine derivatives were synthesised by
      reacting ethoxymethyleneamino derivatives with hydrazides. Their structures were
      elucidated by IR, (1)H NMR, and (13)C NMR spectroscopic data and elemental
      analyses. Antigenotoxic activity of the obtained compounds was tested in
      Escherichia coli PQ37 by using the SOS chromotest.

PMID- 17224205
TI  - Synthesis and characterization of cobalt(II), nickel(II), copper(II) and zinc(II)
      complexes with Schiff base derived from 4-amino-3-mercapto-6-methyl-5-oxo-1,2,4
      triazine.
AB  - A few (1:1) and (1:2) metal complexes of cobalt(II), nickel(II), copper(II) and
      zinc(II) have been isolated with ligand derived from the condensation of 4-amino
      3-mercapto-6-methyl-5-oxo-1,2,4-triazine with 2-acetylpyridine (L(1)) and
      characterized by elemental analysis, conductivity measurements, infrared,
      electronic, (1)H NMR spectral data, magnetic and thermogravimetric analyses. Due
      to insolubility in water and most of the common organic solvents and infusibility
      at higher temperatures, all the complexes are thought to be polymeric in nature.
      A square-planar geometry was suggested for copper(II) and octahedral proposed for
      cobalt(II), nickel(II) and zinc(II). Some of the chemically synthesized compounds
      have been screened in vitro against the three Gram-positive (Staphylococcus
      aureus, Staphylococcus epidermidis and Bacillus subtilis) and two Gram-negative
      (Salmonella typhi and Escherichia coli) organisms. It is observed that the
      coordination of metal ion has pronounced effect on the microbial activities of
      the ligand. The metal complexes have higher antimicrobial effect than the free
      ligands.

PMID- 17224206
TI  - Gorse GJ, et al. "Immunogenicity and tolerance of ascending doses of a
      recombinant protective antigen (rPA102) anthrax vaccine: a randomized, double
      blinded, controlled, multicenter trial" [Vaccine 24 (2006) 5950-5959].
AB  - In the study reported by Gorse et al. a unique, educational opportunity was lost.
      The vaccine and biodefense communities almost experienced the rare chance in a
      Phase I study to scientifically compare head-to-head an early-stage,
      investigational recombinant anthrax vaccine (rPA102) with the safe, effective and
      already FDA-licensed anthrax vaccine, AVA (BioThrax). The authors take a stab at
      making safety and immunogenicity comparisons between the candidate vaccine and
      AVA (BioThrax) but the study design and analytical approach makes this
      inappropriate. Inaccurate and poorly substantiated editorial comments in the
      paper's introduction compound these methodological problems. The reader is
      presented with a series of false and misleading statements about AVA (BioThrax).
      Out-of-date sources are relied upon and these references are offered to the
      reader as the best evidence available when more current papers with up-to-date
      information and data exist. Additionally, the conclusions in several original
      contributions are misrepresented in this paper by Gorse et al. Issues with
      protocol and bias notwithstanding, the single most compelling observation from
      this trial could be that the response of those subjects in this study population
      (n=19) who received AVA on the altered schedule and route of two doses of AVA
      (BioThrax) delivered intramuscularly (IM) in just 4 weeks mounted a robust immune
      response. Given the more than 30 year history of the safe and effective use of
      AVA (BioThrax) as well as the more current data on AVA (BioThrax) a strong case
      can be made for continued funding to investigate the feasibility of adding
      another route of delivery (IM) and optimizing the schedule for this already FDA
      licensed vaccine.

PMID- 17224207
TI  - Molecular diagnosis of viral diseases, present trends and future aspects A view
      from the OIE Collaborating Centre for the Application of Polymerase Chain
      Reaction Methods for Diagnosis of Viral Diseases in Veterinary Medicine.
AB  - The emergence and re-emergence of transboundary animal diseases (TADs), e.g.,
      foot-and-mouth disease, classical swine fever and the highly pathogenic avian
      influenza strongly indicate the need for the development of powerful and robust
      new diagnostic methods. The experiences of an OIE-Collaborating Centre and of two
      EU project consortia are summarised on the diagnostic application of gel-based
      PCR, general PCR systems, phylogeny, molecular epidemiology, real-time PCR
      (TaqMan, Molecular Beacons, Primer-Probe Energy Transfer), amplification without
      thermocycling (Invader), multiplex PCR, nucleic acid extraction and pipetting
      robotics, automation and quality control, including internal controls. By
      following the steps of OIE validation, the diagnostic assays are nationally and
      internationally standardised. The development of padlock probes and microarrays,
      as well as ultra rapid PCR and sequencing methods is further improving the
      arsenal of nucleic acid based molecular diagnosis. Further trends of diagnostic
      development are also mentioned, in order to combat TADs and other viral
      infections more effectively in the future.

PMID- 17224209
TI  - Prospective immunization of the endangered California condors (Gymnogyps
      californianus) protects this species from lethal West Nile virus infection.
AB  - West Nile virus (WNV) has caused significant morbidity and mortality in humans,
      mammals, and both native and exotic birds in North America since its emergence in
      New York City in 1999 and its subsequent spread westward. Prior to the arrival of
      WNV to the western United States, prospective vaccination was conducted for the
      entire population of endangered California condors, both in captivity and in the
      wild. Here we show that this vaccine is safe for condors, stimulates protective
      immunity in adults, nestlings, and newly hatched chicks. Most importantly, we
      demonstrate protection of captive birds exposed to naturally circulating WNV
      during the 2004 transmission season. The prospective vaccination of the entire
      population of California condors before the arrival of WNV has thus potentially
      saved this endangered species from subsequent lethal WNV encephalitis, and
      possible extinction.

PMID- 17224208
TI  - Challenges in the successful control of the avian coccidia.
AB  - Eimeria species infect livestock in a host-specific manner and are the cause of
      the disease, coccidiosis. Control of Eimeria species is essential and is
      currently dominated by chemotherapy; with vaccination using formulations of live
      wild-type or attenuated parasites an increasing option. A new generation of
      subunit, live-vector or DNA vaccination strategies is being sought and
      determining the identity of suitable antigens remains difficult. Some past and
      present methods of controlling avian coccidia are discussed briefly and we
      describe progress with a novel approach to identify immunoprotective antigens as
      vaccine candidates.

PMID- 17224210
TI  - Co-delivery of plasmid-encoded cytokines modulates the immune response to a DNA
      vaccine delivered by in vivo electroporation.
AB  - In this study, in vivo electroporation of a DNA vaccine adjuvanted with plasmids
      encoding different cytokines was investigated in large animals. Sheep were
      injected intramuscularly with a DNA vaccine encoding an antigen of Haemonchus
      contortus (pNPA) and plasmids encoding different cytokines followed by in vivo
      electroporation. Plasmids (pCI) carrying the genes of different cytokines
      including ovine IL-4(pCI-IL4), IL-10(pCI-IL10), GM-CSF(pCI-GMCSF), and MCP
      1alpha(pCI-MCP1alpha), and pCI-IL4+pCI-GMCSF were co-delivered with pNPA. The
      results showed that co-delivery of pCI-GMCSF or pCI-IL4+pCI-GMCSF significantly
      enhanced both antibody responses and T cell proliferation responses to the
      antigen after two DNA immunisations compared to co-delivery of pCI. In contrast,
      antibody responses of the sheep that received pCI-IL10 were decreased
      significantly. Other cytokine expressing plasmids did not significantly alter the
      measured immune responses. Furthermore, co-delivery of pCI-GMCSF increased IgG2
      response more than IgG1 responses, suggesting a Th1 bias. However, the increase
      in IgG2 over IgG1 was less apparent when co-delivery of pCI-IL4 with pCI-GMCSF.
      Interestingly, the co-delivery of pCI-IL4 alone did not increase the IgG1 titre,
      suggesting that both pCI-GMCSF and pCI-IL4 are required for optimal IgG1
      production. Thus, co-delivery of plasmid-encoded cytokine genes with in vivo
      electroporation has the ability to effectively modulate immune responses to a DNA
      vaccine in a large animal.

PMID- 17224211
TI  - Protection against heartwater by DNA immunisation with four Ehrlichia ruminantium
      open reading frames.
AB  - We have reported previously that a recombinant DNA vaccine consisting of four
      Ehrlichia ruminantium (Welgevonden) open reading frames (ORFs) known as the 1H12
      cocktail provided protection against a virulent E. ruminantium (Welgevonden)
      needle challenge in sheep. In this study, we have investigated the vaccine
      effectiveness of two other cocktails of E. ruminantium (Welgevonden) ORFs, as
      well as single ORFs from the 1H12 cocktail, to protect sheep against a virulent
      needle challenge with the homologous strain. Each individual 1H12 ORF provided
      protection, but all the animals vaccinated with the other cocktails succumbed to
      the challenge.

PMID- 17224212
TI  - Analysis of strategies to successfully vaccinate infants in developing countries
      against enterotoxigenic E. coli (ETEC) disease.
AB  - Enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of
      diarrhoea in the world, annually affecting up to 400,000,000 children under 5
      years of age living in developing countries (DCs). Although ETEC possesses
      numerous antigens, the relatively conserved colonization factor (CF) antigens and
      the heat labile enterotoxin (LT) have been associated with protection and most
      vaccine candidates have exploited these antigens. A safe and effective vaccine
      against ETEC is a feasible goal as supported by the acquisition of protective
      immunity. The success of an ETEC vaccine targeting infants and children in DCs
      will depend on a combination of maximally antigenic vaccine preparations and
      regimens for their delivery which will produce optimal immune responses to these
      antigens. Vaccine candidates having a high priority for accelerated development
      and clinical testing for eventual use in infants would include inactivated ETEC
      or Shigella hybrids expressing ETEC antigens as well as attenuated ETEC strains
      which express the major CF antigens and LT toxin B-subunit, as well as attenuated
      Shigella, Vibrio cholerae and Salmonella typhi hybrids engineered to deliver
      antigens of ETEC. Candidates for an ETEC vaccine would have to meet the minimal
      requirement of providing at least 50% protection against severe disease in DCs
      during the first 2 years of life. The critical roadblock to achieving this goal
      has not been the science as much as the lack of a sufficiently funded and focused
      effort to bring it to realization. However, a Product Development Partnership to
      overcome this hurdle could accelerate the time lines towards when control of ETEC
      disease in DCs is substantially closer.

PMID- 17224214
TI  - Multicenter comparative study of a new ELISA, PLATELIA RABIES II, for the
      detection and titration of anti-rabies glycoprotein antibodies and comparison
      with the rapid fluorescent focus inhibition test (RFFIT) on human samples from
      vaccinated and non-vaccinated people.
AB  - The envelope glycoprotein G of rabies virus induces the production of
      neutralising antibodies, which are important in protection against rabies.
      Therefore, titration of anti-envelope glycoprotein antibodies is a good indicator
      of the degree of immunity in people during anti-rabies treatment or after
      vaccination. According to the World Health Organization (WHO) guidelines, a
      booster vaccine dose should be given if the rabies antibody titre falls below 0.5
      IU/ml. Titration of anti-rabies antibodies is also useful for plasma centers in
      the preparation and standardization of human anti-rabies gamma-globulins for
      therapeutic use and to a lesser extent for the diagnosis of rabies in human sera
      and cerebrospinal fluid (CSF). This paper presents a new enzyme-linked
      immunosorbent assay (ELISA), PLATELIA RABIES II, developed for rabies envelope
      glycoprotein antibody detection or titration and its comparison to the current
      reference method (RFFIT). The data collected during validation of the test in a
      multicenter study are analysed to give a sound overall knowledge of the
      capabilities of the PLATELIA RABIES II, for instance specificity, linearity,
      accuracy, precision, detection limit and quantitation limit. To this aim, human
      serum samples from a total of 1348 vaccinated or non-vaccinated people were
      tested in parallel using the new ELISA and the RFFIT for the presence of anti
      rabies antibodies. Data generated indicate a linear relationship across the range
      of titration between the two methods. The sensitivity reaches 98.6% and the
      specificity 99.4%. This study indicates that this new ELISA test is as sensitive
      and specific as the current standardized reference method. The method is simple,
      safe, rapid and can be considered as a useful alternative to the neutralisation
      test.

PMID- 17224213
TI  - Long-lasting specific antibodies against P277 induced by mucosal administration
      of P277 repeat sequences carried by Hsp65 in the absence of adjuvants.
AB  - To improve the weak immunogenicity of peptide P277, the recombinant expression
      plasmid pET28-Hsp65-6 x P277 was constructed by inserting 5 x P277 which was
      amplified by PCR into the vector pET28-Hsp65-P277. It was transformed into
      Escherichia coli BL21 (DE3) and the fusion protein (Hsp65-6 x P277) was expressed
      effectively as soluble protein after inducing by lactose. The fusion protein was
      purified by means of cell disruption, ammonium sulfate precipitation, double
      distilled H2O dialysis, DEAE52-cellulose column chromatography, and then used to
      immunize female NOD mice with three i.n. inoculations in the absence of
      adjuvants. Serum samples from the immunized mice were collected at 3 weeks
      interval. Antibodies against P277 and HSP65 were detected in immunized mice sera
      by enzyme-linked immunosorbent assay (ELISA) and Western blot. Specific
      antibodies were successfully induced and lasted for more than 20 weeks in animals
      immunized with the fusion protein via intranasal route even in the absence of
      adjuvants.

PMID- 17224215
TI  - Vaccination of chickens against Campylobacter.
AB  - The gram-negative bacterium Campylobacter is the leading cause of bacterial
      entero-colitis in humans and is associated with the occurrence of life
      threatening auto-immune based neurological disorders. Chickens, which are often
      heavily colonized with Campylobacter without signs of pathology, are considered
      the most important source for human infection. Although vaccination is a well
      established and effective method to combat various microbes in poultry, a
      commercial vaccine against Campylobacter has not yet been developed. For the
      development of such a vaccine, three main challenges can be identified: (1) the
      identification of novel cross-protection-inducing antigens, (2) the induction of
      a rapid, potent immune response, and (3) the development of novel adjuvants to
      further stimulate immunity against Campylobacter. The rapidly emerging knowledge
      of the biology of Campylobacter in combination with the recent advances in the
      fields of molecular vaccinology and immunology provide the required setting for
      the development of an effective vaccine against Campylobacter in poultry.

PMID- 17224216
TI  - Lung pathology and immediate hypersensitivity in a mouse model after vaccination
      with pertussis vaccines and challenge with Bordetella pertussis.
AB  - While evaluating vaccine efficacy against clinical Bordetella pertussis isolates
      in mice, after challenge vaccinated mice showed increased lung pathology with
      eosinophilia, compared to challenged, non-vaccinated animals. This led us to
      study bacterial clearance, lung pathology, lung TNF-alpha expression, and
      parameters of immediate hypersensitivity (IH), being serum IgE levels, eosinophil
      numbers in the bronchoalveolar lavage fluid, and ex vivo IL-4, IL-5, IL-10, IL
      13, and IFN-gamma production by the bronchial lymph node cells. BALB/c mice
      received a combined Diphtheria (D), Tetanus (T), Poliomyelitis, and whole-cell
      Pertussis vaccine (WCV), a combined D, T, and three-component acellular Pertussis
      vaccine (ACV), aluminium hydroxide adjuvant, or PBS, 28 and 14 days before B.
      pertussis infection. Similarly treated non-infected mice were taken as a control.
      Infection induced pathology; this induction was stronger after (especially WCV)
      vaccination. WCV but not ACV vaccination induced TNF-alpha expression after
      challenge. After challenge, IH parameters were strongly increased by (especially
      ACV) vaccination. Vaccinated IL-4 KO mice showed similar clearance and pathology,
      in the absence of IgE and with reduced numbers of eosinophils. Vaccinated (Th1
      deficient) T-bet KO mice showed reduced clearance and similar pathology. In
      summary, after challenge vaccination increased lung pathology, TNF-alpha
      expression (only WCV), and IH parameters. Th1 cells were critical for clearance.

PMID- 17224217
TI  - Therapeutic effect of hepatitis B surface antigen-antibody complex is associated
      with cytolytic and non-cytolytic immune responses in hepatitis B patients.
AB  - To study the responses of chronic hepatitis B patients to yeast-derived HBsAg
      HBIG complexes (YIC) and the mechanisms involved, twenty HBeAg-positive chronic
      hepatitis B patients were immunized with 60microg of YIC or alum as the control
      at 4-week intervals, for 24 weeks. Five of ten patients responded to 60microg YIC
      immunization showing > or =2 logs decrease of serum HBV DNA with loss or marked
      reduction of HBeAg and appearance of anti-HBe; two of these patients developed
      anti-HBs. Flares of alanine aminotransferase were observed in 4 of the 5
      responders, and in 2 out of 10 control patients. HBsAg-stimulated peripheral
      blood mononuclear cells (PBMCs) secreted Th1/Th2 cytokines around 24 weeks after
      immunization. Dendritic cells incubated with YIC showed the highest levels of IL
      12 secretion and up-regulation of functional markers. Thus, the therapeutic
      effect of YIC is associated with cytolytic and non-cytolytic responses in
      patients.

PMID- 17224218
TI  - Assessment of the potency and potential immunomodulatory effects of the measles
      mumps rubella and varicella vaccine in infants.
AB  - This study compared the potency and immunomodulatory effects of measles mumps
      rubella (MMR) vaccine given to infants alone or in combination with varicella
      (MMR and V). In an additional group, MMR vaccination was delayed 42 days to
      permit analysis of potential effects on underlying maturation of systemic immune
      functions. Assessment of immunity to the vaccines indicated consistent antibody
      production coupled with mixed Th1/Th2 memory, and no significant differences
      between vaccine groups or to the group who had their MMR vaccination delayed.
      Parallel analyses of cytokine responses to phytohaemagglutinin and tetanus toxoid
      did not detect any "bystander" effects of the vaccines on systemic immunity.

PMID- 17224219
TI  - Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV
      1 Env/Gag-Pol-Nef antigens of clade C.
AB  - Recombinants based on the attenuated vaccinia virus strains MVA and NYVAC are
      considered candidate vectors against different human diseases. In this study we
      have generated and characterized in BALB/c and in transgenic HHD mice the
      immunogenicity of two attenuated poxvirus vectors expressing in a single locus
      (TK) the codon optimized HIV-1 genes encoding gp120 and Gag-Pol-Nef (GPN)
      polyprotein of clade C (referred as MVA-C and NYVAC-C). In HHD mice primed with
      either MVA-C or NYVAC-C, or primed with DNA-C and boosted with the poxvirus
      vectors, the splenic T cell responses against clade C peptides spanning gp120/GPN
      was broad and mainly directed against Gag-1, Env-1 and Env-2 peptide pools. In
      BALB/c mice immunized with the homologous or the heterologous combination of
      poxvirus vectors or with Semliki forest virus (SFV) vectors expressing gp120/GPN,
      the immune response was also broad but the most immunogenic peptides were Env-1,
      GPN-1 and GPN-2. Differences in the magnitude of the cellular immune responses
      were observed between the poxvirus vectors depending on the protocol used. The
      specific cellular immune response triggered by the poxvirus vectors was Th1 type.
      The cellular response against the vectors was higher for NYVAC than for MVA in
      both HHD and BALB/c mice, but differences in viral antigen recognition between
      the vectors was observed in sera from the poxvirus-immunized animals. These
      results demonstrate the immunogenic potential of MVA-C and NYVAC-C as novel
      vaccine candidates against clade C of HIV-1.

PMID- 17224220
TI  - Poliomyelitis: concerns for polio-free countries.

PMID- 17224221
TI  - The safety and efficacy of the oral rabies vaccine SAG2 in Indian stray dogs.
AB  - India is one of the countries with the highest prevalence of human rabies
      throughout the world. Dogs are primarily responsible for rabies transmission.
      Among them, stray dogs play a major role in that country. Parenteral vaccination
      programmes are insufficient to eliminate rabies partly due to difficulties in
      establishing satisfactory immunisation coverage in the dog population in view of
      the high proportion of stray dogs. Oral vaccination may be a useful adjunct to
      parenteral vaccination by increasing dog vaccination coverage. Safety,
      immunogenicity and efficacy of Rabidog SAG2 bait were evaluated in Indian stray
      dogs in captivity. Safety of SAG2 was demonstrated by the absence of adverse
      clinical sign, salivary excretion and absence of replication of the vaccine
      strain in brain and salivary glands of 21 vaccinated dogs, even when
      immunodepressed. Efficacy was shown 109 days post-vaccination after challenge
      with a highly virulent street rabies virus which killed all five controls whereas
      all nine vaccinated dogs survived, despite the fact that only five out of nine
      had seroconverted before challenge.

PMID- 17224223
TI  - Collapsed scaphoid non-union with dorsal intercalated segment instability and
      avascular necrosis treated by vascularised wedge-shaped bone graft and fixation.
AB  - Patients with the specific problem of a collapsed Nakamura volar type, scaphoid
      synovial pseudarthrosis with avascular necrosis on both magnetic resonance
      imaging and intraoperative inspection were studied to determine the ability of a
      trapezoidal wedge-shaped structural bone graft vascularised by the 1,2
      intercompartmental supraretinacular artery to simultaneously achieve correction
      of the scaphoid dimension and a high union rate. Fifteen patients with this
      specific problem were followed for a mean of 32.1 months and achieved union in
      all cases at a mean of 11.5 weeks. Improvements were seen postoperatively in
      wrist flexion and extension, grip strength, degree of dorsal intercalated segment
      instability and degree of scaphoid collapse. Two complications relating to the
      fixation technique occurred. Although technically difficult, it is possible to
      achieve a high rate of union for scaphoid pseudarthrosis while correcting
      substantial collapse deformity by the use of a structural, wedge-shaped,
      vascularised bone graft.

PMID- 17224222
TI  - Reliability of the pulp nail bone (PNB) classification for fingertip injuries.
AB  - Evans and Bernardis proposed the 'PNB classification', by which a fingertip
      injury is classified according to each structure: pulp P, nail N, bone B. The
      objective of this study was to assess the inter-observer reliability,
      repeatability and accuracy of PNB. One hundred patients presenting with a
      fingertip injury were included prospectively, photographed, then classified in
      randomly chosen orders by nine independent observers. A third were drawn randomly
      and classified a second time to measure repeatability. A reference classification
      was also provided by one of the authors of the PNB system. Classifications agreed
      with the reference in 59% of injuries for P, 55% for N and 54% for B. The Kappa
      values for inter-observer agreement were 0.520 for P, 0.512 for N, and 0.504 for
      B; for intra-observer agreement, they were 0.616 for P, 0.658 for N, and 0.577
      for B. Although levels of agreement are comparable with results found for other
      classifications, they are insufficient for use of the PNB classification without
      improvement.

PMID- 17224224
TI  - Use of Integra in a paediatric upper extremity degloving injury.
AB  - Dermal substitutes such as Integra have been used in surgery since 1981. This
      product was developed to cover large skin burns but it may have a role in
      reconstructive upper limb surgery. In upper extremity avulsion, the choice of
      skin cover depends on many variables. Dermal substitute is an alternative when
      split-thickness skin grafting is appropriate. We present a case of severe upper
      limb avulsion, or 'degloving', in a child of 9 years old which was treated
      successfully with Integra. Integra is particulary useful in growing children to
      cover large skin losses.

PMID- 17224225
TI  - Motor recovery and the breathing arm after brachial plexus surgical repairs,
      including re-implantation of avulsed spinal roots into the spinal cord.
AB  - Forty-four patients with severe traction brachial plexus avulsion injuries were
      studied following surgical repairs. In eight patients, re-implanting avulsed
      spinal roots directly to the spinal cord was performed with other repairs and
      motor recovery in the proximal limb was similar to that achieved by conventional
      nerve grafts and transfers when assessed using the MRC clinical grades, Narakas
      scores, EMG and Transcranial Magnetic Stimulation (TMS). Thirty-four of the 37
      patients had co-contractions of agonist and antagonist muscle groups. Spontaneous
      contractions of limb muscles in synchrony with respiration, the "breathing arm",
      were noted in 26 of 37 patients: in three patients, the source of the breathing
      arm was from spinal cord re-connection, providing evidence of regeneration from
      the CNS to the periphery. Our study shows that re-connection of avulsed spinal
      roots can produce good motor recovery and provides a clinical model for
      developing new treatments which may enhance nerve regeneration.

PMID- 17224226
TI  - A comparison between subjective outcome score and moderate radial shortening
      following a fractured distal radius in patients of mean age 69 years.
AB  - Radial shortening has been associated with a poor functional outcome following a
      fractured distal radius. This paper reports the results of evaluation by the
      patient rated wrist evaluation (PRWE) score of 60 patients (mean age 69) who
      underwent closed reduction and K-wire fixation of distal radial fractures. In
      this patient group, no association was found between moderate radial shortening,
      either at injury or fracture union, and this subjective outcome score. A
      significant association was found between the assessment of these fractures by
      the Frykman classification and the PRWE score (P=0.01).

PMID- 17224227
TI  - Re: The cellular effect of a single interrupted suture on tendons.

PMID- 17224228
TI  - Heavy metal accumulation in trees growing on contaminated sites in Central
      Europe.
AB  - Metal-accumulating woody species have been considered for phytoextraction of
      metal-contaminated sites. We investigated Zn and Cd accumulation in tissues of
      adult trees and associated herbaceous species collected from contaminated areas
      in Central Europe. We found considerable Cd and Zn accumulation in various
      willow, poplar and birch species with up to 116mgCdkg(-1) and 4680mgZnkg(-1) in
      leaves of Salix caprea. Annual variation of Cd and Zn concentrations in leaves of
      Salix caprea were small, indicating that data obtained in different years can be
      compared. Metal concentrations in leaves were not related to total (aqua regia)
      or labile (1M NH(4)NO(3) extract) concentrations in soil but the accumulation
      factors (leaf concentration: soil concentration) for Cd and Zn followed an
      inverse log type function. Metal partitioning between tissues showed a minimum in
      the wood, with increasing concentrations of Cd and Zn towards the leaves and fine
      roots.

PMID- 17224229
TI  - Immunomodulatory effects of mono-, di-, and trimethylphenols in mice.
AB  - The relationship of air pollutants with the increasing prevalence of allergic
      diseases is a matter of concern in developed countries. In this study, the
      immunomodulatory effects of mono-, di-, and trimethylphenols in mice were
      examined as regards two aspects. First, whether or not these chemicals act as
      sensitizers was evaluated by local lymph node assay. Of the 13 methylphenols
      tested, three dimethylphenol isomers (2,4-DMP, 2,5-DMP, and 3,4-DMP) were found
      to induce auricular lymphocyte proliferation after dermal application on both
      ears of mice. Cytokine production patterns in the supernatants of cultured
      auricular lymphocytes from mice showed these methylphenols to be contact
      sensitizers. Second, the effects of methylphenols on cytokine production profiles
      were examined using cultured splenocytes from immunologically naive mice. Under
      subtoxic conditions, eight methylphenols inhibited interferon-gamma (IFN-gamma)
      production significantly, while the effect on intreluekin-4 (IL-4) production was
      moderate, resulting in higher IL-4/IFN-gamma ratios in all of the tested
      chemicals, with the most prominent effect shown by 2,6-DMP. These results suggest
      that several methylphenols, especially dimethylphenol isomers, have potencies
      that affect the immune system, being immunogens themselves or modulators of the
      Th1/Th2 cytokine balance.

PMID- 17224230
TI  - A prospective manikin-based observational study of telephone-directed
      cardiopulmonary resuscitation.
AB  - INTRODUCTION: Bystander cardiopulmonary resuscitation (CPR) significantly
      improves the outcome from sudden cardiac arrest (SCA) and is therefore encouraged
      by offering telephone instructions to the bystander. The effectiveness of this
      technique was examined in a manikin-based study. METHODS: Subjects performed CPR
      on an instrumented adult manikin by following Advanced Medical Priority Dispatch
      System v11.1 (AMPDS) instructions given by telephone from a different room.
      RESULTS: Fifty-one volunteers (26 males, median age 56, range 27-76 years) with
      no previous experience of CPR were recruited. No volunteers followed the entire
      instructions correctly. Forty percent were unable to open the airway, only 18%
      achieved a median inspiration time of 2 s or greater and only 30% delivered tidal
      volumes within the range 700-1000 ml. Chest compressions were performed at a
      median rate of 52 min-1 with only 4% of subjects achieving a rate of 100 min-1.
      Depth of compression was also inadequate in 88% of subjects and hand positioning
      was incorrect in a third of subjects. The median duty cycle was 46% and there
      were significant delays between the commencement of the AMPDS protocol and the
      delivery of the first breath (123 s) and first chest compression (163 s).
      DISCUSSION: Few bystanders perform CPR satisfactorily and further work is
      necessary to improve the effectiveness of telephone CPR instructions.

PMID- 17224231
TI  - Is the polycystic ovary syndrome associated with chronic inflammation per se?
AB  - OBJECTIVE: The aim of the present study was to evaluate serum concentrations of
      tumor necrosis factor-alpha (TNF-alpha), TNF-soluble receptors, and IL-6 in obese
      women without additional diseases and obese women with polycystic ovary syndrome
      (PCOS). STUDY DESIGN: The study group consisted of 39 obese women with PCOS and
      34 age-matched obese women without additional disease were included as controls.
      Blood glucose, total cholesterol, HDL-cholesterol, and triglycerides were
      measured by the enzymatic procedure. Plasma insulin, follicle-stimulating hormone
      (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS),
      androstenedione, total and free testosterone, cortisol, progesterone, 17OH
      progesterone, estradiol, and sex hormone binding globulin (SHBG) were measured by
      a commercial radioimmunoassay (RIA). Tumor necrosis factor-alpha (TNF-alpha),
      soluble TNF receptors (sTNFRs), and IL-6 were determined by an ELISA. RESULTS: We
      did not observe any differences in serum concentrations of TNF-alpha between
      obese women with and without PCOS. Serum concentrations of sTNFR1 and sTNFR2 were
      significantly higher in PCOS patients compared with controls; however, serum
      concentrations of IL-6 were significantly lower in PCOS patients. CONCLUSIONS:
      Our findings suggest that PCOS is not associated with chronic inflammation.

PMID- 17224232
TI  - A multivariate statistical analysis of surface water chemistry data--the Ankobra
      Basin, Ghana.
AB  - R-mode hierarchical cluster and principal component analysis (PCA) were
      simultaneously applied to surface water hydrochemical data from three different
      locations, Ankwaso, Dominase and Prestea, along the Ankobra Basin, Ghana, to
      extract principal factors corresponding to the different sources of variation in
      the hydrochemistry, with the objective of defining the main controls on the
      hydrochemistry at the basin scale. Using the Kaiser criterion, principal
      components (PC) were extracted from the data and rotated using varimax
      normalization, for each location. The varimax rotation ensured that variation in
      the data was maximized for easy interpretation of the results. The analysis
      reduced 30, 33 and 33 data points, respectively, for Ankwaso, Dominase and
      Prestea to four, three and four PC representing the sources of variation in the
      hydrochemistry at the three different locations. Though the PC analysis proved to
      be more robust at unveiling the sources of variation in the hydrochemistry than
      the R-mode hierarchical cluster analysis (HCA), the combined use of both
      techniques resulted in more reliable interpretations of the hydrochemistry. On
      the basis of these analyses, the hydrochemistry of the basin is controlled
      largely by the weathering of minerals (silicates, carbonates, gypsum and apatite)
      from the underlying meta-sediments of the Birimian and Tarkwaian Systems, and the
      decay of organic matter from the heavily forested regions. Concentrations of the
      major chemical parameters are within naturally acceptable limits and do not pose
      threats to the local ecology and humans. There is no strong evidence of high
      anthropogenic impacts on the major anions and cations used for this research,
      though there are variations at the different locations studied. The
      hydrochemistry at Ankwaso is principally controlled by the weathering of silicate
      minerals, whereas those of Dominase and Prestea are, respectively, influenced by
      precipitation and domestic wastewaters, and the decay of organic matter.

PMID- 17224233
TI  - Bilateral occipital infarcts associated with carotid atherosclerosis and a
      persistent hypoglossal artery.
AB  - The persistent hypoglossal artery (PHA) is the second most common persistent
      embryological carotid-basilar connection and usually represents an incidental
      finding in cerebral arteriograms. The hypoglossal artery connects the primordial
      carotid artery with the longitudinal neural arteries, which later form the
      basilar artery. The PHA leaves the internal carotid artery as an extracranial
      branch, enters the skull through the anterior condyloid foramen, the hypoglossal
      canal and joins the caudal portion of the basilar artery. We report magnetic
      resonance and digital subtraction angiography findings in the first case of
      bilateral occipital infarctions associated with PHA and carotid atherosclerosis.
      The probable mechanism underlying bilateral occipital infarcts was embolism from
      the carotid territory to the posterior cerebral arteries. PHA may present a
      challenge in diagnosis and management of patients with carotid atherosclerosis
      and vertebrobasilar ischemia.

PMID- 17224234
TI  - Acute central cord syndrome with bodybuilder sign.
AB  - We describe a 81-year-old man who after falling face forward and hyperextending
      his neck suffer an acute cervical spinal cord injury consistent with acute
      traumatic central cord syndrome (ATCCS) who developed a peculiar posture with arm
      abduction at the shoulders and flexion at the elbows and wrists resembling the
      pose of a bodybuilder.

PMID- 17224235
TI  - The additive effect of p53 Arg72Pro and RNASEL Arg462Gln genotypes on age of
      disease onset in Lynch syndrome patients with pathogenic germline mutations in
      MSH2 or MLH1.
AB  - p53 and the prostate-cancer-susceptibility gene RNASEL are tumour suppressor
      genes involved in apoptosis. We have previously reported that the common,
      functionally different variants Arg72Pro in p53 and Arg462Gln in RNASEL are
      associated with the age of disease onset of colorectal cancer in Lynch syndrome
      patients. To assess the combined effect of both variants, we screened 246
      unrelated Lynch syndrome patients with a pathogenic germline mutation either in
      MSH2 (n=138) or in MLH1 (n=108) and colorectal cancer as first tumour, and 245
      healthy controls. The global log rank test revealed significant differences in
      the age of disease onset for the genotypes of each variant (p=0.0176 for p53 and
      p=0.0358 for RNASEL) and for the combined genotypes of both variants (p=0.0174).
      The highest difference in median age of disease onset was seen between
      homozygotes for the wild-types in both genes (42years [range 22-75]) and
      homozygotes for the variant alleles in both genes (30years [range 26-47]). A
      multivariate Cox regression model indicated that only the p53 and RNASEL
      genotypes had a significant influence on age of disease onset (p=0.016 for p53
      and p=0.014 for RNASEL) in an additive mode of inheritance, and that the effects
      of both variants are purely additive, which supports the notion that the p53 and
      RNaseL pathways do not interact. These findings may be relevant for preventive
      strategies in Lynch syndrome.

PMID- 17224236
TI  - Recognition of the physiological actions of the triphasic EMG pattern by a
      dynamic recurrent neural network.
AB  - Triphasic electromyographic (EMG) patterns with a sequence of activity in agonist
      (AG1), antagonist (ANT) and again in agonist (AG2) muscles are characteristic of
      ballistic movements. They have been studied in terms of rectangular pulse-width
      or pulse-height modulation. In order to take into account the complexity of the
      EMG signal within the bursts, we used a dynamic recurrent neural network (DRNN)
      for the identification of this pattern in subjects performing fast elbow flexion
      movements. Biceps and triceps EMGs were fed to all 35 fully-connected hidden
      units of the DRNN for mapping onto elbow angular acceleration signals. DRNN
      training was supervised, involving learning rule adaptations of synaptic weights
      and time constants of each unit. We demonstrated that the DRNN is able to
      perfectly reproduce the acceleration profile of the ballistic movements. Then we
      tested the physiological plausibility of all the networks that reached an error
      level below 0.001 by selectively increasing the amplitude of each burst of the
      triphasic pattern and evaluating the effects on the simulated accelerating
      profile. Nineteen percent of these simulations reproduced the physiological
      action classically attributed to the 3 EMG bursts: AG1 increase showed an
      increase of the first accelerating pulse, ANT an increase of the braking pulse
      and AG2 an increase of the clamping pulse. These networks also recognized the
      physiological function of the time interval between AG1 and ANT, reproducing the
      linear relationship between time interval and movement amplitude. This task
      dynamics recognition has implications for the development of DRNN as diagnostic
      tools and prosthetic controllers.

PMID- 17224237
TI  - Intranuclear immunolocalization of 14-3-3 protein isoforms in brains with
      spinocerebellar ataxia type 1.
AB  - Immunolocalization of 14-3-3 protein isoforms, one of the interacters with ataxin
      1, was investigated in spinocerebellar ataxia type 1 (SCA 1) brains using isoform
      specific antibodies. Samples from the pons and from the cerebellum of four SCA1
      cases and three controls were studied. The intensity of the immunoreactivity (IR)
      and its subcellular topography were analyzed. In control subjects, granular
      immunoreactivity for an epitope common to all known isoforms of 14-3-3 proteins
      (14-3-3 COM) found in the cytoplasm of some pontine and dentate nucleus neurons
      was weak. It was observed in some Purkinje cells, while its intensity varied.
      Many nuclei of those neurons and Purkinje cells of SCA1 were intensely
      immunopositive for 14-3-3 COM, while it was less in their cytoplasm. Expanded
      polyglutamine epitope was colocalized to 14-3-3 COM epitope in some pontine
      neurons, sometimes accumulated in intranuclear inclusion-like structures. This
      findings support previous reports that 14-3-3 proteins stabilize mutant ataxin 1
      in nucleus and possibly lead to neurodegeneration. However, nuclear localization
      of 14-3-3 proteins in SCA1 brains was dependent on its isoforms, i.e. pontine
      neurons intensely positive for beta, Purkinje cells for tau and dentate nucleus
      neurons for both, while all of those neurons were consistently positive for zeta
      isoform, although sigma isoform tended to be located in the cytoplasm. Nuclear
      accumulation and isoform- and region-dependent subcellular localizations of 14-3
      3 proteins may be related to SCA1 pathology, which exhibits marked regional
      variability.

PMID- 17224238
TI  - Perineal scalds from drive through restaurants: a public health hazard.

PMID- 17224239
TI  - The influence of group III metabotropic glutamate receptor stimulation by
      (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid on the parkinsonian-like
      akinesia and striatal proenkephalin and prodynorphin mRNA expression in rats.
AB  - Group III metabotropic glutamate receptors (mGluRs) are widely distributed in the
      basal ganglia, especially on the terminals of pathways which seem to be
      overactive in Parkinson's disease. The aim of the present study was to determine
      whether (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid (ACPT-1), an
      agonist of group III mGluRs, injected bilaterally into the globus pallidus (GP),
      striatum or substantia nigra pars reticulata (SNr), can attenuate the haloperidol
      induced catalepsy in rats, and whether that effect was related to modulation of
      proenkephalin (PENK) or prodynorphin (PDYN) mRNA expression in the striatum.
      Administration of ACPT-1 (0.05-1.6 microg/0.5 microl/side) caused a dose-and
      structure-dependent decrease in the haloperidol (0.5 mg/kg i.p. or 1.5 mg/kg
      s.c.)-induced catalepsy whose order was as follows: GP>striatum>SNr. ACPT-1,
      given alone to any of those structures, induced no catalepsy in rats. Haloperidol
      (3 x 1.5 mg/kg s.c.) significantly increased PENK mRNA expression in the
      striatum, while PDYN mRNA levels were not affected by that treatment. ACPT-1 (3 x
      1.6 microg/0.5 microl/side) injected into the striatum significantly attenuated
      the haloperidol-increased PENK mRNA expression, whereas administration of that
      compound into the GP or SNr did not influence the haloperidol-increased striatal
      PENK mRNA levels. Our results demonstrate that stimulation of group III mGluRs in
      the striatum, GP or SNr exerts antiparkinsonian-like effects in rats. The
      anticataleptic effect of intrastriatally injected ACPT-1 seems to correlate with
      diminished striatal PENK mRNA expression. However, since the anticataleptic
      effect produced by intrapallidal and intranigral injection of ACPT-1 is not
      related to a simultaneous decrease in striatal PENK mRNA levels, it is likely
      that a decrease in enkephalin biosynthesis is not a necessary condition to obtain
      an antiparkinsonian effect.

PMID- 17224240
TI  - Connections of the caudal anterior cingulate cortex in rabbit: neural circuitry
      participating in the acquisition of trace eyeblink conditioning.
AB  - The caudal anterior cingulate cortex (cAC) is an essential component of the
      circuitry involved in acquisition of forebrain-dependent trace eyeblink
      conditioning. Lesions of the cAC prevent trace eyeblink conditioning [Weible AP,
      McEchron MD, Disterhoft JF (2000) Cortical involvement in acquisition and
      extinction of trace eyeblink conditioning. Behav Neurosci 114(6):1058-1067]. The
      patterns of activation of cAC neurons recorded in vivo suggest an attentional
      role for this structure early in training [Weible AP, Weiss C, Disterhoft JF
      (2003) Activity profiles of single neurons in caudal anterior cingulate cortex
      during trace eyeblink conditioning in the rabbit. J Neurophysiol 90(2):599-612].
      The goal of the present study was to identify connections of the portion of the
      rabbit cAC previously demonstrated to be involved in trace eyeblink conditioning,
      using the neuronal tract tracer wheat germ agglutinin conjugated to horseradish
      peroxidase, to better understand how the cAC contributes to the process of
      associative learning. Reciprocal connections with the claustrum provide a route
      for the transfer of sensory information between the cAC and neocortical and
      allocortical regions also involved in learning. Connections with components of
      the basal forebrain cholinergic system are described, with relevance to the
      proposed attentional role of the cAC. Reciprocal and unidirectional connections
      were in evidence in multiple thalamic regions, including the medial dorsal
      nucleus, which have been implicated in a variety of conditioning paradigms.
      Anterograde connections with the caudate and lateral pontine nuclei provide
      access to forebrain motor and brainstem sensory circuitry, respectively. The
      relevance of these connections to acquisition of the trace conditioned reflex is
      discussed.

PMID- 17224241
TI  - Modulation of acid-sensing ion channels by Cu(2+) in cultured hypothalamic
      neurons of the rat.
AB  - Acid-sensing ion channels (ASICs) are known to distribute throughout the nervous
      system and serve important roles in various physiological and pathological
      processes. However, the properties of ASICs in the hypothalamus, an important
      region of diencephalon, are little known. We herein used whole-cell patch-clamp
      recordings to characterize proton-induced cation currents in cultured
      hypothalamic neurons of the rat, and attributed these transient inward currents
      to ASICs based on their electrophysiological and pharmacological properties. We
      further examined the effects of Cu(2+), the third most abundant trace element, on
      ASICs in hypothalamic neurons. Our results showed that this divalent cation
      reversibly and concentration-dependently inhibited the amplitude of ASIC
      currents, and slowed down the desensitization of ASIC channels. Our results also
      displayed that Cu(2+) modulated ASICs independent of change in membrane potential
      and extracellular protons, suggesting a noncompetitive mechanism. Furthermore,
      micromolar concentration of Cu(2+) attenuated the acid-induced membrane
      depolarization. Taken together, our data demonstrate a modulatory effect of
      Cu(2+) on ASICs in native hypothalamic neurons and suggest a role of this
      endogenous metal ion in negatively modulating the increased neuronal membrane
      excitability caused by activation of ASICs.

PMID- 17224242
TI  - Motor planning of arm movements is direction-dependent in the gravity field.
AB  - In the present study we analyzed kinematic and dynamic features of arm movements
      in order to better elucidate how the motor system integrates environmental
      constraints (gravity) into motor planning and control processes. To reach this
      aim, we experimentally manipulated the mechanical effects of gravity on the arm
      while maintaining arm inertia constant (i.e. the distribution of the mass around
      the shoulder joint). Six subjects performed single-joint arm movements (rotation
      around the shoulder joint) in both sagittal (upward, U, versus downward, D) and
      horizontal (left, L, versus right, R) planes, at different amplitudes and from
      different initial positions. Under these conditions, shoulder gravitational
      torques (SGTs) significantly varied when arm movements were performed in the
      sagittal but not in the horizontal plane. Contrary to SGTs, arm inertia remained
      constant and similar for both horizontal and sagittal planes since subjects
      performed arm movements with only one degree of freedom. All subjects, whatever
      the movement direction, appropriately scaled shoulder joint kinematic parameters
      according to movement amplitude. Furthermore, peak velocity and movement duration
      were equivalent for both horizontal and sagittal planes. Interestingly, some
      kinematic parameters significantly differed according to U/D but not L/R
      directions. Specifically, acceleration duration was greater for D than U
      movements, while the opposite was true for peak acceleration. Consequently,
      although vertical and horizontal arm movements shared a general common strategy
      (i.e. scaling law), the kinematic asymmetries between U and D arm movements,
      especially those that reflect central planning process (i.e. peak acceleration),
      indicated different motor intentions regarding the direction of the upcoming
      movement. These findings indicate that the interaction of the arm with the
      dynamics of the environment is internally represented during the generation of
      arm trajectories.

PMID- 17224243
TI  - A subgroup of spinocerebellar ataxias defective in DNA damage responses.
AB  - A subgroup of human autosomal recessive ataxias is also characterized by
      disturbances of eye movement or oculomotor apraxia. These include ataxia
      telangiectasia (A-T); ataxia telangiectasia like disorder (ATLD); ataxia
      oculomotor apraxia type 1 (AOA1) and ataxia oculomotor apraxia type 2 (AOA2).
      What appears to be emerging is that all of these have in common some form of
      defect in DNA damage response which could account for the neurodegenerative
      changes seen in these disorders. We describe here sensitivity to DNA damaging
      agents in AOA1 and evidence that these cells have a defect in single strand break
      repair. Comparison is made with what appears to be a novel form of AOA (AOA3)
      which also shows sensitivity to agents that lead to single strand breaks in DNA
      as well as a reduced capacity to repair these breaks. AOA3 cells are defective in
      the DNA damage-induced p53 response. This defect can be overcome by incubation
      with the mdm2 antagonists, nutlins, but combined treatment with nutlins and DNA
      damage does not enhance the response. We also show that AOA3 cells are deficient
      in p73 activation after DNA damage. These data provide further evidence that
      different forms of AOA have in common a reduced capacity to cope with damage to
      DNA, which may account for the neurodegeneration observed in these syndromes.

PMID- 17224245
TI  - Oster rediscovered--mega-dose folate for symptomatic atherosclerosis.
AB  - Thirty years ago, Kurt Oster promulgated the avant-garde theory that bovine
      xanthine oxidase, absorbed intact from homogenized milk, promoted atherogenesis
      by oxidatively damaging membrane plasmalogens. Under the mistaken impression that
      folic acid is a xanthine oxidase inhibitor, he administered high-dose folate (80
      mg daily) to hundreds of patients afflicted with symptomatic atherosclerosis, and
      reported marked improvements in angina, intermittent claudication, and wound
      healing; he also suspected that this regimen was decreasing heart attack risk.
      The xanthine oxidase theory has since fallen by the wayside, but there is now
      evidence that folic acid can lessen endothelial oxidative stress by improving the
      function of "uncoupled" nitric oxide synthase deficient in tetrahydrobiopterin.
      In light of these new findings, a properly controlled assessment of Oster's mega
      dose folate therapy is warranted.

PMID- 17224246
TI  - Progressive glycosylation of albumin and its effect on the binding of
      homocysteine may be a key step in the pathogenesis of vascular damage in diabetes
      mellitus.
AB  - The majority of diabetes research to date has rightly focussed on the direct
      effects of hyperglycaemia on tissues and a number of theories relating to the
      pathogenesis of vascular disease have been proposed. This research is important
      as until methods are found to achieve glycaemic control in all diabetic patients,
      prophylactic interventions to prevent vasculopathy will be required. One of the
      major blood proteins, human albumin is known to be covalently modified by
      extended incubation with glucose, leading to an impairment of ligand binding. One
      of the important ligands bound by albumin is homocysteine. There is increasing
      and compelling clinical, experimental and epidemiological evidence that
      homocysteine, and in particular the free unbound fraction, is vasculotoxic. If
      homocysteine binding to albumin is impaired by increasing glycosylation of
      albumin then either drugs which reduce homocysteine levels (pyridoxine, folic
      acid and cobalamin) or inhibit glycosylation (aminoguanidines) may be of benefit
      in the prevention of vascular damage in diabetic patients.

PMID- 17224244
TI  - Hypercortisolemic depression is associated with the metabolic syndrome in late
      life.
AB  - INTRODUCTION: Depression has been hypothesized to be associated with metabolic
      abnormalities which increase the risk of cardiovascular disease (CVD) and
      diabetes. Such a link could be due to increased HPA-axis activity. This study
      investigates the cross-sectional relationship between depression, urinary
      cortisol and metabolic syndrome in an older population. METHODS: Data are from
      867 participants of the InChianti Study, aged 65 years. Depressive symptoms were
      assessed using the CES-D scale; cortisol levels were determined in 24-h urine
      samples. Metabolic syndrome was defined as three or more of the following:
      abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure,
      and high fasting glucose. RESULTS: Clinically relevant depressed mood (CES-D20)
      was present in 20.6% of the sample, and 24.5% had the metabolic syndrome. After
      adjustment for sociodemographics and health indicators, depression score (per SD
      increase: OR=1.20, 95% CI=1.02-1.41) and urinary cortisol level (per SD increase:
      OR=1.23, 95% CI=1.01-1.51) were significantly associated with presence of
      metabolic syndrome. There was, however, a significant interaction (p=0.003)
      between depressed mood and urinary cortisol in the probability of having
      metabolic syndrome. The odds of metabolic syndrome in persons with both depressed
      mood and urinary cortisol excretion in the highest tertile was 1.84 (95% CI=1.02
      3.34) compared to persons with neither condition. DISCUSSION: This study suggests
      a synergistic relationship between depression, cortisol and metabolic syndrome.
      Hypercortisolemic depression may constitute a specific risk group for the
      metabolic syndrome.

PMID- 17224247
TI  - Evaluation of ELISA based on the conserved and functional middle region of
      nucleocapsid protein to detect distemper infection in dogs.
AB  - A 287bp fragment from the middle region of the nucleocapsid protein of canine
      distemper virus (CDV) was amplified from the conjunctival samples of distemper
      infected dogs and was cloned into pRSET B vector. The recombinant protein was
      expressed as a 16-kDa-fusion protein with histidine tag in E. coli. Sera of
      distemper-infected and vaccinated dogs contained IgG antibodies against the
      purified recombinant protein as observed by enzyme linked immunosorbent assays
      (ELISA) and showed a strong correlation (r=0.882, p<0.0001 at 95% CI) and good
      agreement (kappa=0.718) with the conventional tissue culture viral antigen based
      ELISA. Further, the results of recombinant protein based ELISA and Western
      blotting with the sera from the infected and vaccinated dogs correlated well
      (kappa=0.8226). These findings recommend the use of the recombinant protein in
      the serodiagnosis of canine distemper virus infection in dogs.

PMID- 17224248
TI  - Mycoplasma mycoides subsp. mycoides biotype large colony isolates from healthy
      and diseased goats: prevalence and typing.
AB  - Most severe goat mycoplasmosis outbreaks in France are caused by Mycoplasma
      mycoides subsp. mycoides biotype LC (MmmLC). However, MmmLC can also be recovered
      from ear canals of healthy goats or from bulk milk collected in herds showing no
      clinical signs of mycoplasmosis. To improve our understanding of how MmmLC
      strains are balanced between pathogenic ones and asymptomatically carried ones,
      descriptive epidemiological data were analysed, together with the genomic
      fingerprints of isolates generated using pulsed-field gel electrophoresis (PFGE).
      PGFE analyses were performed with isolates collected from the ear canals of goats
      or bulk milk in healthy herds, from individual clinical cases in different
      diseased herds at different times, and within a single herd during a severe
      outbreak, from various body sites including the ear canals at autopsy. Results
      showed that each isolate collected in healthy herds yielded a unique and
      characteristic PFGE profile. Isolates from diseased herds had profiles that were
      distinct for each outbreak and the group of 41 isolates from a single severe
      outbreak had 2 predominant PFGE profiles that persisted throughout the outbreak.
      These data suggest that while several distinct isolates are carried by healthy
      animals, only a few are responsible for the clinical signs observed within one
      herd during an outbreak. Whether this reflects differences in virulence between
      different field strains of MmmLC remains to be demonstrated.

PMID- 17224249
TI  - Urinary excretion of acrylamide and metabolites in Fischer 344 rats and B6C3F(1)
      mice administered a single dose of acrylamide.
AB  - Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic,
      mutagenic to somatic and germ cells, and carcinogenic in mice and rats. AA is
      also formed during cooking in many commonly consumed starchy foods. Our previous
      toxicokinetic investigations of AA and its genotoxic metabolite, glycidamide
      (GA), in rodents showed that AA is highly bioavailable from oral routes of
      administration, is widely distributed to tissues, and that the dietary route, in
      particular, favors metabolism to GA. Formation and accumulation of mutagenic GA
      DNA adducts in many tissues support the hypothesis that AA is carcinogenic in
      rodent bioassays through metabolism to GA. The current investigation describes
      the quantification of 24 h urinary metabolites, including free AA and GA and
      their mercapturic acid conjugates (AAMA and GAMA, respectively), using LC/MS/MS
      in F344 rats and B6C3F(1) mice following a dose of 0.1 mg/kg bw given by
      intravenous, gavage, and dietary routes of administration. Similar groups of
      rodents were used previously for serum/tissue toxicokinetic and adduct
      determinations (DNA and hemoglobin). The goal was to investigate relationships
      between urinary and circulating biomarkers of exposure, toxicokinetic parameters
      for AA and GA, and tissue GA-DNA adducts in rodents from single doses of AA.
      Significant linear correlations were observed between urinary levels of AA with
      AAMA and GA with GAMA in the current data sets for rats and mice. Concentrations
      of AA and AAMA correlated significantly with average AUC values determined
      previously for AA in groups of rats and mice similarly dosed with AA. Urinary GA
      and GAMA concentrations showed significant correlations with average AUC values
      for GA and liver GA-DNA adducts determined previously in rats and mice similarly
      dosed with AA. Despite statistical significance, considerable inter-animal
      variability was observed in all urinary measurements, which limited the degree of
      correlation with either average toxicokinetic or biomarker data collected from
      different groups of animals. These results suggest that urinary measurements of
      AA and its metabolites may be useful for prediction of internal exposures to AA
      and GA.

PMID- 17224250
TI  - Furan is not genotoxic in the micronucleus assay in vivo or in vitro.
AB  - Furan, a potential human carcinogen, is formed during heat-treatment of food.
      Previous studies of the genotoxicity of furan have given disparate results.
      Hence, there is a need for complementary data to clarify the mechanism behind the
      carcinogenicity of furan. In this study, we have used the flow cytometer-based
      micronucleus assay in mice and the cytokinesis-block micronucleus assay in human
      lymphocytes to investigate the genotoxic potential of furan. Three in vivo
      experiments were performed: intraperitoneal or subcutaneous injection of furan in
      male Balb/C mice (0-300 and 0-275 mg/kg body weight, respectively) and
      intraperitoneal injection of male CBA mice (0 and 225 mg/kg body weight). No
      increased level of micronucleated erythrocytes was detected in any of the in vivo
      experiments. In the in vitro setup, human lymphocytes from two donors were
      treated with furan in concentrations from 0 to 100 mM, either with or without
      metabolic activation (liver homogenate from rat). In parity with the in vivo
      results there was no significant increase in the frequency of micronucleated
      cells here either. As neither the in vivo nor the in vitro studies disclose any
      significant increase in the micronucleus frequency after treatment with furan,
      our results support that the carcinogenicity of furan is caused by a non
      genotoxic mechanism.

PMID- 17224251
TI  - Prevention of noise- and drug-induced hearing loss with D-methionine.
AB  - A number of otoprotective agents are currently being investigated. Various types
      of agents have been found in animal studies to protect against hearing loss
      induced by cisplatin, carboplatin, aminoglycosides, or noise exposure. For over a
      decade we have been investigating D-methionine (D-met) as an otoprotective agent.
      Studies in our laboratory and others around the world have documented D-met's
      otoprotective action, in a variety of species, against a variety of ototoxic
      insults including cisplatin-, carboplatin-, aminoglycoside- and noise-induced
      auditory threshold elevations and cochlear hair cell loss. For cisplatin-induced
      ototoxicity, protection of the stria vascularis has also been documented. Further
      D-met has an excellent safety profile. D-met may act as both a direct and
      indirect antioxidant. In this report, we provide the results of three
      experiments, expanding findings in D-met protection in three of our translational
      research areas: protection from platinum based chemotherapy-, aminoglycoside- and
      noise-induced hearing loss. These experiments demonstrate oral D-met protection
      against cisplatin-induced ototoxicity, D-met protection against amikacin-induced
      ototoxicity, and D-met rescue from permanent noise-induced hearing loss when D
      met is initiated 1h after noise exposure. These studies demonstrate some of the
      animal experiments needed as steps to translate a protective agent from bench to
      bedside.

PMID- 17224252
TI  - Exploring efferent-mediated DPOAE adaptation in three different guinea pig
      strains.
AB  - The aims of this study were to explore the correlation between DPOAE adaptation
      magnitude in three different guinea pig strains to examine if the genetic
      component affects the DPOAE adaptation magnitude. It was also to investigate the
      correlation between strains with certain characteristics i.e. reduced
      susceptibility to noise, and early onset of age-dependent hearing loss and the
      DPOAE adaptation magnitude. The animals were anaesthetized and the 2f1-f2 DPOAE
      (f1=8k Hz, and f2/f1=1.2) adaptation was established with a minimum of 144
      combinations of f1; f2 where f1 was held fixed and f2 was varied in 1 dB or 0.4
      dB steps. The DPOAE adaptation magnitude was defined as the difference between
      maximum positive level and the maximum negative level. ABRs were conducted at
      different age-groups (at 4, 6.3, and 12.5k Hz) to evaluate the progress of
      hearing thresholds by age. There was a significant difference between strains
      regarding the hearing loss at one year of age. There was no significant
      difference in DPOAE adaptation magnitude between strains included in this study
      and from this we conclude that the DPOAE adaptation magnitude is not a predictor
      for the susceptibility to noise trauma, or early onset of age-dependent hearing
      loss, using the methods described in this paper.

PMID- 17224254
TI  - CT colonography: techniques, indications, findings.
AB  - Computed tomographic colonography (CTC) is a minimally invasive technique for
      imaging the entire colon. Based on a helical thin-section CT of the cleansed and
      air-distended colon, two-dimensional and three-dimensional projections are used
      for image interpretation. Several clinical improvements in patient preparation,
      technical advances in CT, and new developments in evaluation software have
      allowed CTC to develop into a powerful diagnostic tool. It is already well
      established as a reliable diagnostic tool in symptomatic patients. Many experts
      currently consider CTC a comparable alternative to conventional colonoscopy,
      although there is still debate about its sensitivity for the detection of colonic
      polyps in a screening population. This article summarizes the main indications,
      the current techniques in patient preparation, data acquisition and data analysis
      as well as imaging features for common benign and malignant colorectal lesions.

PMID- 17224253
TI  - Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in
      aged mice.
AB  - Oxidative damage of biomolecules increases with age and is postulated to be a
      major causal factor of various physiological function disorders. Consequently,
      the concept of anti-age by antioxidants has been developed. Lycium barbarum
      fruits have been used as a traditional Chinese herbal medicine and the data
      obtained in in vitro models have clearly established the antioxidant potency of
      the polysaccharides isolated from the fruits. In the present study, the age
      dependent changes in the antioxidant enzyme activity, immune function and lipid
      peroxidation product were investigated and effect of Lycium barbarum
      polysaccharides on age-induced oxidative stress in different organs of aged mice
      was checked. Lycium barbarum polysaccharides (200, 350 and 500 mg/kg b.w. in
      physiological saline) were orally administrated to aged mice over a period of 30
      days. Aged mice receiving vitamin C served as positive control. Enzymatic and non
      enzymatic antioxidants, lipid peroxides in serum and tested organs, and immune
      function were measured. Result showed that increased endogenous lipid
      peroxidation, and decreased antioxidant activities, as assessed by superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total
      antioxidant capacity (TAOC), and immune function were observed in aged mice and
      restored to normal levels in the polysaccharides-treated groups. Antioxidant
      activities of Lycium barbarum polysaccharides can be compable with normal
      antioxidant, vitamin C. Moreover, addition of vitamin C to the polysaccharides
      further increased the in vivo antioxidant activity of the latter. It is concluded
      that the Lycium barbarum polysaccharides can be used in compensating the decline
      in TAOC, immune function and the activities of antioxidant enzymes and thereby
      reduces the risks of lipid peroxidation accelerated by age-induced free radical.

PMID- 17224255
TI  - Coccygeal movement: assessment with dynamic MRI.
AB  - PURPOSE: Chronic coccygodynia is a difficult problem diagnostically and
      therapeutically. Moreover, there is no deep knowledge especially in the field of
      imaging of chronic coccygodynia. In this study several possible measurements are
      proposed, which all are able to demonstrate coccygeal movement during defecation,
      in order to assess coccygeal mobility using dynamic MRI during maximum
      contraction and during straining-evacuation. MATERIALS AND METHODS: A dynamic MRI
      study of the pelvic floor was performed in 112 patients. Five methods of
      measurement were assessed. Coccygeal movements were determined through the
      evaluation of three angles pair and two different distances measured during the
      phase of maximum contraction and during the phase of straining-evacuation.
      Results were compared according to age, sex, parity and experience of minor
      trauma. No patient included in the study had coccygodynia. Measurements taken by
      two radiologist were compared to determine interobserver agreement. RESULTS: The
      maximum measurement values of the two distances are homogeneous, between 9 and
      9.4mm. The maximum measurement values of the three angles showed a difference
      that is between 21 degrees and 38 degrees . Two of three angles showed a major
      measurement values in the funtional texts. In only one patient the coccyx was not
      mobile. CONCLUSION: Our dynamic MRI study indicates that the coccyx is mobile
      during defecation and that it is possible to demonstrate coccygeal excursions by
      assessing the difference between its positions at maximum contraction and during
      straining-evacuation. The measurement methods used in this study for evaluating
      coccygeal movements resulted in variably sized observed differences, but all
      yielded statistically significant results in demonstrating coccygeal excursion.
      Among the five measurement methods, two resulted in the largest differences. Our
      data indicate no correlation between coccygeal movements and age, sex, parity,
      minor trauma and coccygodynia.

PMID- 17224256
TI  - Understanding the degradation pathway of a poorly water-soluble drug formulated
      in PEG-400.
AB  - VX-497 is a poorly water-soluble compound. It is formulated in PEG-400 and
      encapsulated in softgel capsules. Although the drug product is stable at
      refrigerated conditions, many degradation peaks have been observed at accelerated
      storage conditions. An investigation utilizing high performance liquid
      chromatography-mass spectrometry (HPLC-MS) was conducted to understand the
      degradation mechanism of the active pharmaceutical ingredient (VX-497) in PEG-400
      formulation. Results revealed that the degradation was mainly caused by the
      reaction between VX-497 with moisture (hydrolysis) and PEG-400 (PEGylation). The
      numerous degradation peaks observed in the samples stored at accelerated
      conditions were PEG adducts covalently attached to portions of the VX-497
      molecule, which were confirmed by comparison with synthetic markers.
      Investigation also found that an impurity, which was present in the VX-497 drug
      substance, reacted with PEG-400 following the same reaction mechanism, and
      generated additional impurities in the VX-497 drug product. By changing the
      process for drug substance synthesis, pure batches of VX-497 were obtained.
      Furthermore, it was found that the reaction between VX-497 and PEG-400 was
      temperature and time dependent. When the drug product was manufactured at 45
      degrees C and the processing time was controlled, the PEG degradants and by
      products were reduced to non-detectable levels, resulting in greatly improved
      drug product quality. This paper presents an integrated effort among analytical,
      process, and formulation scientists on how to develop a better drug product by
      understanding the fundamental issues of the drug product, namely the degradation
      mechanism.

PMID- 17224257
TI  - Evaluation of a modified single-enzyme amplified fragment length polymorphism (SE
      AFLP) technique for subtyping Salmonella enterica serotype Enteritidis.
AB  - Salmonella enterica subsp. enterica serotype Enteritidis is not readily subtyped
      beyond the level of phage type (PT). Pulsed field gel electrophoresis (PFGE) is
      generally acknowledged to be the most discriminating typing method for
      Salmonella, but only a restricted variety of PFGE types has been described for S.
      enterica serotype Enteritidis. In the present study, a modification of the SE
      AFLP typing method was used to investigate both outbreak and apparently sporadic
      isolates of S. enterica serotype Enteritidis belonging to different PTs and/or
      PFGE types. The method proved to be as discriminatory as PFGE when combined with
      phage typing, and provided subtyping data consistent with epidemiological
      information. Although the modified SE-AFLP typing method did not prove to achieve
      a superior discriminatory ability in resolving clusters, it has a high enough
      throughput for use in outbreak investigations. This method can be used in
      combination with other typing methods to obtain epidemiologically relevant
      subtyping data on S. enterica serotype Enteritidis.

PMID- 17224258
TI  - PetG and PetN, but not PetL, are essential subunits of the cytochrome b6f complex
      from Synechocystis PCC 6803.
AB  - The cytochrome b(6)f complex consists of four large core subunits and an
      additional four low molecular weight subunits, the function of which is elusive
      thus far. Here we sought to determine whether small subunits PetG, PetL, and PetN
      are essential for a cyanobacterial cytochrome b(6)f complex. We found that only
      PetL is dispensable, whereas PetG and PetN appear to be essential. Possible roles
      of the small cytochrome b(6)f complex subunits are discussed, and observations
      from our study are compared with previous findings.

PMID- 17224259
TI  - Cultivation-independent assessment of the bacterial diversity of breast milk
      among healthy women.
AB  - Breast milk has been shown to be an excellent and continuous source of commensal
      and potentially probiotic bacteria to the infant gut. Our aim was to evaluate the
      dominant bacteria existing in breast milk of healthy women and the potential role
      of transit through the vagina in the acquisition of breast milk microbiota using
      the 16S rRNA amplified gene approach. Samples of breast milk were aseptically
      collected, at day 7 after delivery, from five mothers whose neonates were born by
      vaginal delivery and from five others who had had their babies by programmed
      elective cesarean section. All mothers were healthy, had a full-term pregnancy
      and breastfed their infants. DNA extracted from biological samples was used as a
      template for PCR amplification of 16S rRNA gene sequences with universal
      bacterial primers; then the PCR products were analyzed by denaturing gradient gel
      electrophoresis (DGGE); finally, clone libraries of 16S rRNA gene sequences from
      4 mothers (2 from each group) were constructed. PCR DGGE patterns and clone
      libraries suggest that each woman had a specific bacterial pattern in her breast
      milk, and confirm, at the molecular level, that breast milk of healthy women is a
      source of commensal bacteria to the infant gut. They also reinforce recent
      molecular studies which have shown that lactic acid bacteria colonization is not
      significantly related to the delivery method.

PMID- 17224260
TI  - Analysis of topoisomerase mutations in fluoroquinolone-resistant and -susceptible
      Campylobacter jejuni strains isolated in Senegal.
AB  - In this study, topoisomerase mutations in ciprofloxacin-resistant and 
      susceptible Campylobacter jejuni were analysed by DNA sequencing. In certain
      ciprofloxacin-resistant C. jejuni, the mechanism of resistance was complex. The
      Thr86-Ala substitution in the GyrA protein appears to play a role in increasing
      the minimum inhibitory concentration of nalidixic acid only. In addition,
      isolates with this amino acid change and those resistant to quinolones but
      lacking a mutation in the GyrA quinolone resistance-determining region could be
      derived from two different clones. Based on gyrA and gyrB polymorphisms, C.
      jejuni isolates from the Dakar region of Senegal appeared to be less diverse than
      those from other countries. Moreover, C. jejuni isolates in Senegal appeared to
      differ from European isolates by lack of a silent mutation at codon 120 of the
      gyrA gene.

PMID- 17224262
TI  - Does metabolic syndrome cause obstructive sleep apnoea?

PMID- 17224261
TI  - Identification of an upstream regulatory element reveals a novel requirement for
      Ind activity in maintaining ind expression.
AB  - A maternally established gradient of nuclear Dorsal protein is the first step in
      subdivision of the Drosophila neurectoderm into stripes of homeodomain gene
      expression. Dorsal in combination with the EGF and TGFbeta signaling pathways are
      key regulators of the expression of the genes ventral nervous system defective
      (vnd), intermediate neuroblasts defective (ind), and muscle segment homeobox
      (msh) in the developing neurectoderm. These three genes encode homeodomain
      transcription factors that can repress each other, which ensures adjacent, non
      overlapping expression domains. Expression of vnd, ind, and msh is maintained
      after decline in EGF and TGFbeta signaling, but the relevant positive
      transcriptional regulators have not yet been defined. Here, we show that Ind can
      bind DNA with the same sequence specificity as its murine ortholog Gsh1. We have
      identified a novel upstream regulatory element at the ind locus containing
      predicted Ind binding sites, and we show that Ind activity is both necessary and
      sufficient for reporter gene expression from this element. We conclude that Ind
      can act as a transcriptional activator, and that positive autoregulation of Ind
      is a mechanism for persistent ind expression within the developing embryonic
      nervous system.

PMID- 17224263
TI  - Leachate recirculation effects on waste degradation: study on columns.
AB  - The purpose of this study is to determine the impact of leachate recirculation on
      the degradation of municipal solid wastes (bioreactor concept). The study was
      carried out using columns containing approximately 50 kg of waste, in order to
      follow waste degradation over a limited time. Three types of waste were studied:
      fresh waste of standard composition, fresh waste of fermentable composition and
      some 8-yr-old waste extracted from a site in France. Measurement of the global
      parameters, such as chemical oxygen demand (COD), volatile acidity, alkalinity,
      leachate conductivity, methane potential of the wastes and biogas production
      monitoring (volume of CO2 and CH4 produced), were carried out. The quantity of
      oxydizable matter and biogas production was increased by the leachate
      recirculation, and the duration of the first degradation phases was reduced in
      all cases. Chloride, ammonium and organic pollution accumulation was observed
      according to the duration of recirculation. After 400 days of degradation, waste
      stabilization seemed to be reached for all of the recirculated columns (COD<300
      mg/L O2, and methane potential reached).

PMID- 17224264
TI  - Trends and problems of solid waste management in developing countries: a case
      study in seven Palestinian districts.
AB  - There is a great interest in solving problems related to municipal solid waste
      (MSW) management in the Palestinian territory. However, few studies have been
      done to assess the extent of these problems and suggest the best alternative
      solutions. This study aims at assessing MSW conditions in the seven major
      districts in northern West Bank, Palestinian territory. The study focuses on
      comparing several MSW management elements (such as collection, budget, and
      disposal) in municipalities, village councils, and refugee camps in the studied
      districts and the problems faced by these institutions in handling the waste. It
      also provides information on MSW collection service availability and waste
      disposal practices in the districts studied. It was found that, although MSW
      collection service was available for 98% of the residents in the areas surveyed,
      no proper treatment or landfill procedure was followed for the collected waste in
      most of these areas. Instead, waste burning in open dumpsites was the most common
      practice. Moreover, due to inefficient collection of waste disposal fees from the
      residents, municipalities were forced to sometimes cut the collection service and
      reduce its labor force, especially in villages. The budget for MSW management was
      between 2% and 8% of the total budget of the municipalities studied, indicating a
      low priority for this issue.

PMID- 17224265
TI  - Anaerobic biogasification of undiluted dairy manure in leaching bed reactors.
AB  - Dry anaerobic digestion of high solids animal manure is of increasing importance
      since conventional slurry digestion is not an effective system for these manures.
      The investment costs for large-size reactors, costs for heating these reactors,
      handling, dewatering, and the disposal of the digested residue decrease the
      benefits of conventional slurry anaerobic digestion for high solids animal
      manure. Even though leaching bed reactors (LBR) constitute a promising option for
      dry anaerobic biogasification of animal manure, no study is cited in the
      literature for animal manure, excluding a single study on cattle waste which
      utilized a similar concept in a different experimental set-up, namely a packed
      bed digester. Therefore, this work was undertaken to investigate the anaerobic
      biogasification of undiluted dairy manure in LBRs. To this purpose anaerobic
      leaching bed reactors (ALBR) packed with a mixture of dairy manure, anaerobic
      seed and wood powder/chips were operated. The ALBRs were fed with water, and the
      leachate that was collected from their effluents was subjected to biochemical
      methane potential (BMP) experiments to determine the biogas production. The
      results revealed that LBRs can successfully be applied to anaerobic digestion of
      undiluted dairy manure with around 25% improvement in biogas production relative
      to conventional (slurry) anaerobic digesters.

PMID- 17224266
TI  - Prospective comparison of 18F-fluorodeoxyglucose positron emission
      tomography/computed tomography and whole-body magnetic resonance imaging in
      staging of advanced malignant melanoma.
AB  - The aim of our study was to compare the overall and site-based accuracy and
      impact on patient management of positron emission tomography/computed tomography
      (PET/CT) and whole-body (wb) magnetic resonance imaging (MRI) in staging of
      advanced melanoma. In a prospective blinded study, 64 patients with American
      Joint Committee on Cancer (AJCC) stage III/IV melanoma underwent 18F
      fluorodeoxyglucose PET/CT and wbMRI. In total 420 lesions were evaluated. The
      overall accuracy of PET/CT was 86.7% compared to 78.8% for wbMRI (P=0.0007).
      PET/CT was significantly more accurate in N-staging and detecting of skin and
      subcutaneous metastases, whereas wbMRI was more sensitive in detecting liver,
      bone and brain metastases. WbMRI was less sensitive but more specific than PET/CT
      in classifying pulmonary lesions. In 41 patients (64%) whole-body imaging caused
      changes of treatment. Whole-body staging of patients with advanced melanoma is
      most accurate by combining wbPET/CT and organ-specific wbMRI including a brain,
      liver and bone marrow protocol.

PMID- 17224267
TI  - EGFR mutations and human papillomavirus in squamous cell carcinoma of tongue and
      tonsil.
AB  - This study was performed to determine the clinical significance of mutations in
      the EGFR (epidermal growth factor receptor) along with their association with
      human papillomavirus (HPV) infections in patients with squamous cell carcinoma of
      the head and neck (HNSCC). Exons 18-21 of the EGFR tyrosine kinase domain were
      sequenced and HPV typing was carried out using the HPV DNA chip in tissues
      obtained from patients with tongue and tonsil cancer. Univariate and multivariate
      analyses were used to identify the significant factors. One hundred and eight
      patients were enrolled. Ten patients (9%) were HPV positive and 17 (16%) had EGFR
      mutations. None of the patients with EGFR mutations were HPV positive. Gender,
      age (<60 years versus 60 years), and smoking history were not associated with
      EGFR mutations. A higher percentage of patients with tonsillar cancer were HPV
      positive than those with tongue cancer (26% and 0%, respectively; P<0.001). EGFR
      mutations were not a significant prognostic factor (P=0.746). HPV-positive
      patients had prolonged survival (P=0.025). Multivariate analysis revealed a
      longer overall survival in HPV-positive patients (P=0.007). EGFR mutations are
      not associated with the HPV-positive status, which may confer a better survival
      outcome. Clinical features of lung cancer patients with EGFR mutations were not
      observed in HNSCC. A further study will be needed to confirm these results.

PMID- 17224268
TI  - Germline mutations of TP53 and BRCA2 genes in breast cancer/sarcoma families.
AB  - The genetic aetiology of familial aggregations of breast cancer and sarcomas has
      been elucidated only in part. In this study, 23 unrelated individuals from
      families with one case of sarcoma and at least one case of breast cancer were
      screened for mutations in the TP53, BRCA1 and BRCA2 genes. Families were
      classified according to their conformity to the criteria defining the Li-Fraumeni
      syndrome (LFS), Li-Fraumeni-like (LFL) syndrome and hereditary breast/ovarian
      cancer (HBOC). Germline TP53 mutations were identified in three instances (13%),
      including one LFS and two LFL families, while none of the non-LFS/non-LFL
      families had a TP53 mutation. Three cases (13%), including one with a TP53
      mutation, carried BRCA2 mutations. Of these, two were observed in LFL/HBOC
      families and the other one in a non-LFS/non-LFL/HBOC family, while none of the
      non-HBOC families tested positive. These findings suggest that the screening of
      BRCA2, in addition to TP53, may be appropriate for the molecular characterisation
      of breast cancer/sarcoma families, with practical implications for counselling
      and clinical management.

PMID- 17224269
TI  - Clusterin over-expression modulates proapoptotic and antiproliferative effects of
      1,25(OH)2D3 in prostate cancer cells in vitro.
AB  - Prostate cancer is the most commonly diagnosed cancer in the majority of western
      countries. Due to their antiproliferative and proapoptotic activity, vitamin D
      analogues have been introduced recently as an experimental therapy for prostate
      cancer. Clusterin (CLU) is a glycoprotein that has two known isoforms generated
      in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, and a
      secretory form (sCLU) is pro-survival. In this study, we analyzed whether
      proapoptotic and antiproliferative effects of 1,25(OH)(2)D(3) on LNCaP prostate
      cancer cells are modulated by expression of sCLU. Using colony forming assay, we
      studied the effect of treatment with different doses of 1,25(OH)(2)D(3) (10(-6),
      10(-7), 10(-10)M) on proliferation of LNCaP cells that were stable transfected
      and over-express sCLU (LNT-1) as compared to empty vector-transfected cells
      (LN/C). We also measured apoptosis using TUNEL assay. sCLU over-expression
      protected against both antiproliferative (30%) and proapoptotic (15%) effects of
      1,25(OH)(2)D(3), although this effect was statistically not significant. In
      conclusion, our findings demonstrate that expression of sCLU modulates growth
      regulatory effects of 1,25(OH)(2)D(3) in prostate cancer indicating that CLU
      interferes with vitamin D signalling pathways.

PMID- 17224270
TI  - 1alpha,25(OH)2D3 is an autocrine regulator of extracellular matrix turnover and
      growth factor release via ERp60 activated matrix vesicle metalloproteinases.
AB  - Growth plate chondrocytes produce proteoglycan-rich type II collagen
      extracellular matrix (ECM). During cell maturation and hypertrophy, ECM is
      reorganized via a process regulated by 1alpha,25(OH)(2)D(3) and involving matrix
      metalloproteinases (MMPs), including MMP-3 and MMP-2. 1alpha,25(OH)(2)D(3)
      regulates MMP incorporation into matrix vesicles (MVs), where they are stored
      until released. Like plasma membranes (PM), MVs contain the 1alpha,25(OH)(2)D(3)
      binding protein ERp60, phospholipase A(2) (PLA(2)), and caveolin-1, but appear to
      lack nuclear Vitamin D receptors (VDRs). Chondrocytes produce
      1alpha,25(OH)(2)D(3) (10(-8)M), which binds ERp60, activating PLA(2), and
      resulting lysophospholipids lead to MV membrane disorganization, releasing active
      MMPs. MV MMP-3 activates TGF-beta1 stored in the ECM as large latent TGF-beta1
      complexes, consisting of latent TGF-beta1 binding protein, latency associated
      peptide, and latent TGF-beta1. Others have shown that MMP-2 specifically
      activates TGF-beta2. TGF-beta1 regulates 1alpha,25(OH)(2)D(3)-production,
      providing a mechanism for local control of growth factor activation.
      1alpha,25(OH)(2)D(3) activates PKCalpha in the PM via ERp60-signaling through
      PLA(2), lysophospholipid production, and PLCbeta. It also regulates distribution
      of phospholipids and PKC isoforms between MVs and PMs, enriching the MVs in
      PKCzeta. Direct activation of MMP-3 in MVs requires ERp60. However, when MVs are
      treated with 1alpha,25(OH)(2)D(3), PKCzeta activity is decreased and PKCalpha is
      unaffected, suggesting a more complex feedback mechanism, potentially involving
      MV lipid signaling.

PMID- 17224272
TI  - Treatment of olive mill waste-water by aerobic biodegradation: an analytical
      study using gel permeation chromatography, ultraviolet-visible and Fourier
      transform infrared spectroscopy.
AB  - Liquid waste from olive oil mills was digested following inoculation with soil
      microorganisms and fractionated through various grades of gel. The fractionation
      showed the range of sizes of the molecules in the waste. In addition, the
      disappearance of the low molecular weight fraction, which is retained by the gel,
      and the increase of the high molecular weight fraction, which is excluded by the
      gel, during the last stages of the microbial treatment, indicates polymerisation
      of the low-molecular-weight subunits. Characterization of the fractions by UV
      visible and FTIR spectroscopy confirmed the increase in their degree of
      polymerisation during the treatment. This is paralleled by a reduction in the
      amount of aliphatic components and a concomitant increase in aromatic structures.

PMID- 17224271
TI  - The phosphatonins and the regulation of phosphate transport and vitamin D
      metabolism.
AB  - Phosphate homeostasis is preserved during variations in phosphate intake by short
      term intrinsic renal and intestinal adaptations in transport processes, and by
      more long-term hormonal mechanisms, which regulate the efficiency of phosphate
      transport in the kidney and intestine. Recently, several phosphaturic peptides
      such as fibroblast growth factor 23 (FGF-23), secreted frizzled-related protein-4
      (sFRP-4), extracellular phosphoglycoprotein (MEPE) and fibroblast growth factor 7
      (FGF-7) have been shown to play a pathogenic role in several hypophosphatemic
      disorders such as tumor-induced osteomalacia (TIO), autosomal dominant
      hypophosphatemic rickets (ADHR), X-linked hypophosphatemic rickets (XLH), the
      McCune-Albright syndrome (MAS) and fibrous dysplasia (FD). These proteins induce
      phosphaturia and hypophosphatemia in vivo, and inhibit sodium-dependent renal
      phosphate transport in cultured renal epithelial cells. Interestingly, despite
      the induction of hypophosphatemia by FGF-23 and sFRP-4 in vivo, serum 1, 25
      dihydroxyvitamin D (1alpha,25(OH)(2)D) concentrations are decreased or remain
      inappropriately normal, suggesting an inhibitory effect of these proteins on 25
      hydroxyvitamin D 1alpha-hydroxylase activity. In FGF-23 knockout mice, 25
      hydroxyvitamin D 1alpha-hydroxylase expression is increased and elevated serum
      1alpha,25(OH)(2)D levels cause significant hypercalcemia and hyperphosphatemia.
      MEPE, however, increases circulating 1alpha,25(OH)(2)D. Circulating or local
      concentrations of these peptides/proteins may regulate 25-hydroxyvitamin D 1alpha
      hydroxylase activity in renal tissues under physiologic circumstances.

PMID- 17224273
TI  - Balancing perspectives on the sentinel node.

PMID- 17224274
TI  - A comparison of outcomes after robotic open extended thymectomy for myasthenia
      gravis.
AB  - OBJECTIVE: The aim of this study was to analyze the effect of the surgical
      approach on surgical and neurologic outcomes after extended thymectomy for
      myasthenia gravis. METHODS: A retrospective analysis of the institutional
      extended thymectomies for myasthenia gravis within the last decade was performed.
      Patients of group A (open access by total median sternotomy; n=10; 1996-2002) and
      of group B (video assisted thoracoscopic surgery approach with the da Vinci
      robotic system; n=9; 2003-2006) did not differ with regard to gender
      distribution, age, body mass index, American Association of Anaesthetists score
      and Osserman classification of myasthenia gravis. Primary endpoints were surgical
      complications and the symptomatic/neurologic outcome of the extended thymectomy.
      Secondary endpoints were operating times and hospital stay. RESULTS: Median
      follow-up was 74+/-23 months in group A and 13+/-10 months in group B. Surgical
      complications occurred in 4 patients in group A (requiring 2 re-interventions)
      and in 1 patient in group B (p<0.05). The median dose of Pyridostigminbromid was
      reduced 3 and 6 months postoperatively in group A to 80% and 60% of the
      preoperative level and in group B to 66% and 60% of the preoperative level,
      respectively. Within the first postoperative year all patients of group B had an
      improvement of their disease whereas 2 patients of group A did not benefit from
      thymectomy or had a worsening of symptoms. Operating times were significantly
      shorter in group A (110 (42-152) min vs 154 (94-312) min, p<0.05), hospital stay
      was significantly shorter in group B (5 (4-15) vs 10 (10-23) days, p<0.05).
      CONCLUSIONS: The results of this small series favour the robotic approach for
      extended thymectomy for myasthenia gravis in respect of both surgical and early
      neurologic outcome. However, prospective randomized trials are required to prove
      a general validity.

PMID- 17224275
TI  - Concomitant aortic valve replacement and coronary bypass: the effect of valve
      type on the blood flow in bypass grafts.
AB  - OBJECTIVE: In cases of aortic valve replacement, the downstream flow profile and
      turbulence in the ascending aorta differ according to the prosthetic aortic valve
      implanted. The objective of this work is to study the influence of prosthetic
      valve type on the flow in the bypass grafts implanted to the ascending aorta in
      cases of concomitant aortic valve replacement and coronary artery bypass.
      METHODS: The study is conducted on 456 patients receiving concomitant aortic
      valve replacement and coronary bypass vein grafts anastomosed to the ascending
      aorta. The patients included in the study received a total number of 725 vein
      grafts, 249 biological aortic valves and 207 mechanical aortic valves.
      Intraoperative transit time flow measurement was done for all bypass grafts and a
      multiple regression model was calculated for the factors influencing the flow in
      the bypass grafts. RESULTS: The mean flow in vein grafts in patients receiving
      biological valves was 49.79+/-26.88 ml/min, while in patients receiving
      mechanical valves it was 46.54+/-26.68 ml/min. The multiple regression model
      revealed that receiving a mechanical valve is an independent risk factor for
      lower flow in the vein grafts. CONCLUSIONS: The type of the aortic valve
      implanted and consequently the downstream flow profile in the ascending aorta do
      affect the flow in the vein grafts in cases of concomitant aortic valve
      replacement and coronary bypass. Receiving a mechanical aortic valve is an
      independent risk factor for lower flow in the vein grafts.

PMID- 17224276
TI  - Effect of low intensity laser interaction with human skin fibroblast cells using
      fiber-optic nano-probes.
AB  - Over the past forty years, many efforts have been devoted to study low power
      laser light interactions with biological systems. Some of the investigations were
      performed in-vitro, on bulk cell populations. Our present work was undertaken to
      apply specially engineered fiber-optic based nano-probes for the precise delivery
      of laser light on to a single cell and to observe production of low power laser
      light induced reactive oxygen species (ROS). A normal human skin fibroblast (NHF)
      cell line was utilized in this investigation and the cells were irradiated under
      two different schemes of exposure: (1) an entire NHF cell population within a
      Petri dish using a fan beam methodology, and (2) through the precise delivery of
      laser energy on to a single NHF cell using fiber-optic nano-probe.
      Photobiostimulative studies were conducted through variation of laser intensity,
      exposure time, and the energy dose of exposure. Laser irradiation induced
      enhancement in the rate of cell proliferation was observed to be dependent on
      laser exposure parameters and the method of laser delivery. The total energy dose
      (fluence) had a greater influence on the enhancement in the rate of cellular
      proliferation than compared to laser intensity. The enhancement in the growth
      rate was observed to have a finite life-time of several days after the initial
      laser exposure. Fluorescent life-time imaging of ROS was performed during the
      nano-based single cell exposure method. The kinetics of ROS generation was found
      to depend strongly on the laser fluence and not on the laser intensity.

PMID- 17224277
TI  - Interleukin-1 receptor antagonist gene polymorphism affects the progression of
      chronic renal failure.
AB  - End-stage renal disease (ESRD) involves an inflammatory process. Interleukin-1
      receptor antagonist (IL-1Ra) and interleukin-1beta gene polymorphisms affect
      susceptibility to the disease in several inflammatory diseases. We investigated
      whether these polymorphisms are involved in ESRD by genotyping DNA from 602
      dialyzed patients and 433 controls with polymerase chain reaction and digestion
      with restriction endonuclease. Allele 2 of the IL-1Ra VNTR polymorphism was
      associated with ESRD (OR=1.46, 95% CI 1.19-1.78). We also found a strong
      association between this allele and recurrent peritonitis in peritoneal dialysis
      patients. Odds ratio for the risk allele was higher compared to entire ESRD group
      (OR=3.6, 95% CI 1.70-7.44). The homozygosity for the allele 2 was associated with
      disease progression, especially in patients with diabetic nephropathy and
      glomerulonephritis. For the patients from these two subgroups having 2.2
      genotype, the mean time from disease onset to ESRD was 1.5 and 2.2 years,
      respectively, compared to 6.4 and 9.8 years for those with 1.1 genotype. The IL
      1Ra allele 2 is associated with ESRD in our dialyzed patients. Our results
      demonstrate for the first time the association of the IL-1Ra allele 2 with faster
      progression to ESRD. If confirmed in other populations, it might be a predictor
      of faster disease progression.

PMID- 17224279
TI  - High-yield expression in Escherichia coli of soluble human MT2A with native
      functions.
AB  - Metallothioneins (MTs) are a family of low molecular weight, cysteine rich heavy
      metal binding proteins with multifunction, such as metal detoxification and
      antioxidation, and are involved in a number of cellular processes including gene
      expression, apoptosis, proliferation and differentiation. However, high yield
      expression of human MT in Escherichia coli has not been established effectively.
      To produce large amounts of human MT protein at low cost, recombinant human
      metallothionein 2A (MT2A) protein with an N-terminal GST tag was successfully
      expressed at high levels in soluble form in E. coli and high purification of it
      was established by affinity chromatography under native conditions. The final
      yield was about 5mg of the recombinant MT2A per liter of bacterial culture with
      the purity of 97.9%. Chemical and functional characteristics analysis of the
      recombinant human MT2A exhibited intact metal binding ability, hydroxyl radical
      scavenging ability and significant protective role against DNA damage caused by
      UVC radiation. Establishment of highly purified recombinant human MT2A protein
      with native characteristics at low cost would improve its function study and wide
      applications in protecting against oxidative damage and UV radiation.

PMID- 17224278
TI  - Identification and characterization of a +1 frameshift observed during the
      expression of Epstein-Barr virus IL-10 in Escherichia coli.
AB  - Epstein-Barr virus IL-10 (ebvIL-10) mimics the biological functions of cellular
      IL-10 including a number of immunoinhibitory activities on diverse immune cells.
      Characterization of ebvIL-10 and several mutants, expressed in Escherichia coli,
      by gel filtration chromatography and mass spectrometry revealed a +1 frameshift
      upon ebvIL-10 expression. The frameshift is caused by the rare AGG codon at ebvIL
      10 Arg159, which is followed by the most inefficient stop signal, UGAC. The
      frameshift was corrected by substituting the rare AGG codon with an abundant
      arginine codon, CGU, or by enhancing the level of tRNA that decodes the AGG
      codon. As a result, ebvIL-10 expression levels increased by approximately 3-fold
      and the purity of the protein improved from 85-95% to 98-99%. The correction of
      the frameshift has been essential for continuing structural and biophysical
      studies of ebvIL-10.

PMID- 17224280
TI  - Efficient automatic noise reduction of electron tomographic reconstructions based
      on iterative median filtering.
AB  - A simple, fast and efficient noise-reduction protocol for three-dimensional
      electron tomographic reconstructions of biological material is presented. The
      approach is based on iterative application of median filtering and shows promise
      for automatic noise reduction as a pre-processor for automated data analysis
      tools which aim at segmentation, feature extraction and pattern recognition. The
      application of this algorithm produces encouraging results for a wide variety of
      experimental and synthetic electron tomographic reconstructions.

PMID- 17224281
TI  - Cortical abnormalities in epilepsy revealed by local EEG synchrony.
AB  - Abnormally strong functional linkage between cortical areas has been postulated
      to play a role in the pathogenesis of partial epilepsy. We explore the
      possibility that such linkages may be manifest in the interictal EEG apart from
      epileptiform disturbances or visually evident focal abnormalities. We analyzed
      samples of interictal intracranial EEG (ICEEG) recorded from subdural grids in
      nine patients with medically intractable partial epilepsy, measuring
      interelectrode synchrony using the mean phase coherence algorithm. This analysis
      revealed areas of elevated local synchrony, or "hypersynchrony" which had
      persistent spatiotemporal characteristics that were unique to each patient.
      Measuring local synchrony in a subdural grid results in a map of the cortical
      surface that provides information not visually apparent on either EEG or
      structural imaging. We explore the relationship of hypersynchronous areas to the
      clinical evidence of seizure localization in each case, and speculate that local
      hypersynchrony may be a marker of epileptogenic cortex, and may prove to be a
      valuable aid to clinical ICEEG interpretation.

PMID- 17224282
TI  - Do serotonin(1-7) receptors modulate short and long-term memory?
AB  - Evidence from invertebrates to human studies indicates that serotonin (5
      hydroxytryptamine; 5-HT) system modulates short- (STM) and long-term memory
      (LTM). This work is primarily focused on analyzing the contribution of 5-HT,
      cholinergic and glutamatergic receptors as well as protein synthesis to STM and
      LTM of an autoshaping learning task. It was observed that the inhibition of
      hippocampal protein synthesis or new mRNA did not produce a significant effect on
      autoshaping STM performance but it did impair LTM. Both non-contingent protein
      inhibition and 5-HT depletion showed no effects. It was basically the non
      selective 5-HT receptor antagonist cyproheptadine, which facilitated STM.
      However, the blockade of glutamatergic and cholinergic transmission impaired STM.
      In contrast, the selective 5-HT(1B) receptor antagonist SB-224289 facilitated
      both STM and LTM. Selective receptor antagonists for the 5-HT(1A) (WAY100635), 5
      HT(1D) (GR127935), 5-HT(2A) (MDL100907), 5-HT(2C/2B) (SB-200646), 5-HT(3)
      (ondansetron) or 5-HT(4) (GR125487), 5-HT(6) (Ro 04-6790, SB-399885 and SB-35713)
      or 5-HT(7) (SB-269970) did not impact STM. Nevertheless, WAY100635, MDL100907, SB
      200646, GR125487, Ro 04-6790, SB-399885 or SB-357134 facilitated LTM. Notably,
      some of these changes shown to be independent of food-intake. Concomitantly,
      these data indicate that '5-HT tone via 5-HT(1B) receptors' might function in a
      serial manner from STM to LTM, whereas working in parallel using 5-HT(1A), 5
      HT(2A), 5-HT(2B/2C), 5-HT(4), or 5-HT(6) receptors.

PMID- 17224283
TI  - Immediate hemodynamic effect of the additional use of the SCD EXPRESS Compression
      System in patients with venous ulcers treated with the four-layer compression
      bandaging system.
AB  - OBJECTIVES: To test the hypothesis that the SCD EXPRESS intermittent pneumatic
      compression applied in combination with a four-layer bandage in patients with
      venous ulcers increases popliteal vein volume flow and velocity. DESIGN: Twenty
      limbs of 18 patients with venous leg ulcers were studied, median age 76 years.
      The Total Volume Flow (TVF) and the Peak Systolic Velocity (PSV) were recorded in
      the popliteal vein using duplex ultrasonography. Measurements were made (i)
      without bandage, (ii) with four layer bandage and (iii) following the application
      of the SCD Compression System on top of a four-layer bandage for at least 15
      minutes. RESULTS: The median VCSS was 17 (range, 12-22) while the median VSDS for
      reflux was 4.5 (range, 1-7.5). The median TVF was 71 mL/min (inter-quartile range
      57-101) without bandage, 112 (IQR 89-148) with four-layer bandage and 291 (IQR
      241-392) with the addition of the SCD System (P<.001, Wilcoxon signed ranks
      test). The median PSV was 8.4 cm/sec (IQR 6.8-14) without bandage, 13 (9.0-19)
      with four-layer bandage and 27 (21-31) with the addition of the SCD System
      (P<.001, Wilcoxon signed ranks test). Both TVF and PSV increased slightly with
      the addition of the four-layer bandage. However, with the addition of the SCD
      System these parameters increased three fold. CONCLUSIONS: The SCD EXPRESS
      Compression System accelerates venous flow in the legs of patients with venous
      ulcers already treated with a four-layer bandage. The combination of four-layer
      compression with the SCD System on healing venous ulcers needs to be tested by a
      clinical effectiveness study.

PMID- 17224284
TI  - Foam sclerotherapy combined with surgical treatment for recurrent varicose veins:
      short term results.
AB  - OBJECTIVE: To study the short term results of combined peroperative foam
      sclerotherapy (PFS) and surgical treatment for recurrent varicose veins. METHODS:
      PFS was used to treat 129 limbs with recurrent varices: 100 great saphenous
      (GSV), 29 small saphenous veins (SSV). Foam was prepared with 1% polidocanol
      mixed with 4 times its volume of air. The 100 GSVs comprised 28 trunks directly
      connected with the femoral vein, 28 connected to a lymph node venous network, 11
      associated with perforators and 33 isolated trunks. The 29 SSVs comprised 4
      trunks directly connected to the popliteal vein, 7 isolated trunks, 15 popliteal
      perforators and 3 recanalisations after SSV stripping. All operations included
      phlebectomies. In twenty limbs re-ligation of the SFJ and 4 SPJs was carried out.
      All were performed under local anaesthesia in an ambulatory setting. Patients
      were assessed clinically and by colour duplex ultrasound after 3 and 40 days
      follow-up. RESULTS: 120 patients (93%) showed complete obliteration of saphenous
      trunks, junctions and varices. The 9 incomplete obliterations were 3 venous
      recanalisations in the SSV compartment and 6 perforators (4 popliteal and 2
      femoral). Two asymptomatic deep venous thromboses were detected by colour duplex
      3 days after operation. CONCLUSION: PFS facilitates surgical treatment of
      recurrent varicose veins. There is a small risk of post-operative deep vein
      thrombosis.

PMID- 17224286
TI  - Genetic mapping of Pyrenophora teres f. teres genes conferring avirulence on
      barley.
AB  - A Pyrenophora teres f. teres cross between isolates 0-1 and 15A was used to
      evaluate the genetics of avirulence associated with barley lines Canadian Lake
      Shore (CLS), Tifang, and Prato. 15A is avirulent on Tifang and CLS, but virulent
      on Prato. Conversely, 0-1 is avirulent on Prato, but virulent on Tifang and CLS.
      Avirulence:virulence on Tifang and CLS segregated 1:1, whereas
      avirulence:virulence on Prato segregated 3:1. An AFLP-based linkage map was
      constructed and used to identify a single locus derived from 15A (AvrHar)
      conferring avirulence to Tifang and CLS. Virulence on Prato was conferred by two
      epistatic genes (AvrPra1 and AvrPra2). AvrPra2 co-segregated with AvrHar, but the
      two genes from opposite parents conferred opposite reactions. This work provides
      the foundation for the isolation of these avirulence genes.

PMID- 17224288
TI  - Differences in electrostatic potential around DNA fragments containing adenine
      and 8-oxo-adenine. An analysis based on regular cylindrical projection.
AB  - Changes of electrostatic potential (EP) around the DNA molecule resulting from
      chemical modifications of nucleotides may play a role in enzymatic recognition of
      damaged sites. Effects of chemical modifications of nucleotides on the structure
      of DNA have been characterized through large scale density functional theory
      computations. Quantum mechanical structural optimizations of DNA fragments with
      three pairs of nucleotides and accompanying counteractions were performed with a
      B3LYP exchange-correlation functional and 6-31G(d,p) basis sets. The "intact" DNA
      fragment contained adenine in the middle layer, while the "damaged" fragment had
      the adenine replaced with 8-oxo-adenine. The electrostatic potential around these
      DNA fragments was projected on a cylindrical surface around the double helix. The
      two-dimensional maps of EP of the intact and damaged DNA fragments were analyzed
      to identify these modifications of EP that result from the occurrence of 8-oxo
      adenine (8oA). It was found that distortions of a phosphate group neighboring 8oA
      and displacements of the accompanying countercation are clearly reflected in the
      EP maps.

PMID- 17224285
TI  - Model systems for the study of heart development and disease. Cardiac neural
      crest and conotruncal malformations.
AB  - Neural crest cells are multipotential cells that delaminate from the dorsal
      neural tube and migrate widely throughout the body. A subregion of the cranial
      neural crest originating between the otocyst and somite 3 has been called
      "cardiac neural crest" because of the importance of these cells in heart
      development. Much of what we know about the contribution and function of the
      cardiac neural crest in cardiovascular development has been learned in the chick
      embryo using quail-chick chimeras to study neural crest migration and derivatives
      as well as using ablation of premigratory neural crest cells to study their
      function. These studies show that cardiac neural crest cells are absolutely
      required to form the aorticopulmonary septum dividing the cardiac arterial pole
      into systemic and pulmonary circulations. They support the normal development and
      patterning of derivatives of the caudal pharyngeal arches and pouches, including
      the great arteries and the thymus, thyroid and parathyroids. Recently, cardiac
      neural crest cells have been shown to modulate signaling in the pharynx during
      the lengthening of the outflow tract by the secondary heart field. Most of the
      genes associated with cardiac neural crest function have been identified using
      mouse models. These studies show that the neural crest cells may not be the
      direct cause of abnormal cardiovascular development but they are a major
      component in the complex tissue interactions in the caudal pharynx and outflow
      tract. Since, cardiac neural crest cells span from the caudal pharynx into the
      outflow tract, they are especially susceptible to any perturbation in or by other
      cells in these regions. Thus, understanding congenital cardiac outflow
      malformations in human sequences of malformations as represented by the DiGeorge
      syndrome will necessarily require understanding development of the cardiac neural
      crest.

PMID- 17224287
TI  - Autonomic activation and pain in response to low-grade mental stress in
      fibromyalgia and shoulder/neck pain patients.
AB  - OBJECTIVE: Psychosocial stress is a risk factor for musculoskeletal pain, but how
      stress affects musculoskeletal pain is poorly understood. We wanted to examine
      the relationship between low-grade autonomic activation and stress-related pain
      in patients with fibromyalgia and localised chronic shoulder/neck pain. METHODS:
      Twenty-three female patients with fibromyalgia, 29 female patients with chronic
      shoulder-neck pain, and 35 healthy women performed a stressful task lasting
      60min. With a blinded study design, we recorded continuous blood pressure, heart
      rate, finger skin blood flow and respiration frequency before (10min), during
      (60min) and after (30min) the stressful task. The physiological responses were
      compared with subjective reports of pain. RESULTS: The increase in diastolic
      blood pressure and heart rate in response to the stressful task were smaller in
      fibromyalgia patients compared with the healthy controls. Furthermore,
      fibromyalgia patients had reduced finger skin blood flow at the end of the
      stressful task compared to healthy controls. We also found an inverse
      relationship between the heart rate response and development and recovery of the
      stress-related pain in fibromyalgia patients. CONCLUSION: We found abnormal
      cardiovascular responses to a 60min long stressful task in fibromyalgia patients.
      Furthermore, we found a negative association between the heart rate response and
      the pain which developed during the stressful task in the fibromyalgia group,
      possibly a result of reduced stress-induced analgesia for fibromyalgia patients.

PMID- 17224289
TI  - Mode of action-based local QSAR modeling for the prediction of acute toxicity in
      the fathead minnow.
AB  - The ultimate intention of quantitative structure-activity relationship (QSAR)
      study in toxicology is to predict the toxic potential of untested compounds with
      great accuracy. As QSAR has been based on the assumption that compounds from the
      same chemical domain will behave in similar manner, the QSAR model built upon the
      analogical chemicals is hypothesized to exhibit better performance than that
      derived from the miscellaneous data set. In this paper, the acute toxicity, 96 h
      LC(50) (median lethal concentration) for the fathead minnow from database
      EPAFHM_v2a_617_1Mar05 served as the interested toxicity endpoint, and the mode of
      action (MOA) in toxic response was employed as a criterion to compartmentalize
      the chemical domains. MOA-based local QSAR models were built by partial least
      squares (PLS) regression for each subset with single mode of action such as
      Narcosis I, Narcosis II or Reactive, and global model was also developed for the
      combined data set containing several subsets above. By comparing the performances
      of these two types of models, the local models were superior to the global model
      in that the relative standard error (R.S.E.) of the former was much lower for
      both the training set and the test set of any subset. In addition, the influence
      of the reliability of MOA determination on the performance of local model was
      also investigated and the statistical results for subsets with MOAs at A and B
      confidence level were better than those at C and D confidence level. Therefore,
      the MOA-based local QSAR models are promising to improve the accuracy of toxicity
      prediction as long as the assessment of MOA is of high reliability.

PMID- 17224290
TI  - Laminin and a Plasmodium ookinete surface protein inhibit melanotic encapsulation
      of Sephadex beads in the hemocoel of mosquitoes.
AB  - In refractory mosquitoes, melanotic encapsulation of Plasmodium ookinetes and
      oocysts is a commonly observed immune response. However, in susceptible
      mosquitoes, Plasmodium oocysts develop extracellularly in the body cavity without
      being recognized by the immune system. Like Plasmodium gallinaceum oocysts,
      negatively charged carboxymethyl (CM)-Sephadex beads implanted in the hemocoel of
      Aedes aegypti female mosquitoes were not usually melanized, but were coated with
      mosquito-derived laminin. Conversely, electrically neutral G-Sephadex beads were
      routinely melanized. Since mosquito laminin coated both CM-Sephadex beads and P.
      gallinaceum oocysts, we hypothesized that laminin prevents melanization of both.
      To test this hypothesis, we coated cyanogen-bromide-activated G-Sephadex beads
      with laminin, recombinant P. gallinaceum ookinete surface protein (PgS28) or
      bovine serum albumin (BSA). Beads were implanted into the abdominal body cavity
      of female Aedes aegypti and retrieved 4 days later. Uncoated controls as well as
      BSA-coated G-Sephadex beads were melanized in a normal manner. However,
      melanization of beads coated with mouse laminin, Drosophila L2-secreted proteins
      or PgS28 was markedly reduced. Fluorescent antibody labeling showed that PgS28
      coated beads had adsorbed mosquito laminin on their surface. Thus, mosquito
      laminin interacting with Plasmodium surface proteins probably masks oocysts from
      the mosquito's immune system, thereby facilitating their development in the body
      cavity.

PMID- 17224291
TI  - Identification of unique genetic markers in Rv0927c among Mycobacterium
      tuberculosis W-Beijing strains.
AB  - Fifty-six clinical isolates of Mycobacterium tuberculosis were analyzed by
      spoligotyping to determine the prevalence of W-Beijing strains. Forty-nine of the
      56 isolates belonged to W-Beijing strains and 7 isolates were non-Beijing
      strains. Comparative two-dimensional gel electrophoresis analysis of protein
      patterns between the W-Beijing and non-Beijing strains identified a unique
      protein Rv0927c that is absent in the former but present in the latter and the
      reference strain M. tuberculosis H37Rv. Compared with 7 non-Beijing clinical
      isolates and H37Rv, all 49 W-Beijing strains had two characteristic mutations, a
      deletion of AGC at nucleotide position 421 of Rv0927c gene encoding a putative
      short dehydrogenase/reductase, causing deletion of serine codon at amino acid
      position 141 and a -127 G-->A mutation in Rv0927c-pstS3 intergenic region,
      resulting in failure to express Rv0927c. Western blot analysis indicated that
      polyclonal antibody raised against H37Rv Rv0927c overexpressed in Escherichia
      coli reacted with non-Beijing strains and H37Rv but not W-Beijing strains.
      Characteristic mutations of Rv0927c that are present in W-Beijing strains can be
      used as a novel genetic marker for rapid molecular typing of M. tuberculosis W
      Beijing strains.

PMID- 17224292
TI  - Mice lacking SIGNR1 have stronger T helper 1 responses to Mycobacterium
      tuberculosis.
AB  - Mycobacterium tuberculosis and the associated disease tuberculosis are health
      risks causing many deaths worldwide each year in humans. M. tuberculosis targets
      dendritic cell (DC)-specific intercellular adhesion molecule-3 grabbing non
      integrin (DC-SIGN) to induce immunosuppression, since interaction of DC-SIGN with
      mycobacterial mannose-capped lipoarabinomannan (ManLAM) induces interleukin (IL)
      10 and prevents DC maturation. We investigated the role of a murine homolog of DC
      SIGN, SIGN Related 1 (SIGNR1), in a model of M. tuberculosis infection using
      SIGNR1 deficient (KO) mice. Although SIGNR1 is expressed by macrophages and not
      by DCs, it also interacts with M. tuberculosis similar to DC-SIGN. Peritoneal
      macrophages from SIGNR1 KO mice produce less IL-10 upon stimulation with ManLAM
      than those from wild-type mice, suggesting that the interaction of ManLAM with
      SIGNR1 can result in immunosuppression similar to its human homolog. Indeed,
      early in infection, we observed increased T cell activity in SIGNR1 KO mice and
      increased IFNgamma production by splenocytes in SIGNR1 KO mice. However, we did
      not detect any differences between WT and KO mice in mycobacterial loads in the
      lungs or distant organs after M. tuberculosis infection resulting in similar
      survival rates. Moreover, we found that SIGNR1 is not present on alveolar
      macrophages of uninfected mice nor is it induced on lung macrophages throughout
      infection. Therefore, our data suggest that although SIGNR1 has a similar binding
      specificity as DC-SIGN, its role is limited during murine M. tuberculosis
      infection.

PMID- 17224293
TI  - Engraftment of cutaneous fibroblasts within synovial membrane in a nonhuman
      primate: short-term results.
AB  - OBJECTIVES: Gene therapy using cells as vectors to achieve secretion of
      therapeutic proteins may hold promise in the treatment of chronic diseases. Cell
      based gene therapy with xenogeneic cells secreting antiinflammatory cytokines (IL
      4, IL-13, or IL-1 receptor type II) has been found effective in mice with
      collagen-induced arthritis (CIA), a model for human rheumatoid arthritis.
      Autologous cells engineered to produce antiinflammatory cytokines were also
      effective in the mouse CIA model. In all these experiments, the cells were
      grafted into the subcutaneous tissue of the back, resulting in systemic
      treatment. To evaluate the feasibility of cell-based gene therapy confined to the
      joints, we performed intraarticular injections of autologous cells in a rhesus
      monkey with CIA, a model more similar to human RA. METHODS: We prepared ex vivo
      cultures of skin fibroblasts from the animal then transfected the cells with a
      plasmid carrying the lacZ gene. We injected these marker cells into
      metacarpophalangeal, metatarsophalangeal, and interphalangeal joints. RESULTS:
      Kinetic evaluation of synovial tissue X-gal labeling, which reflected reported
      gene expression by skin fibroblasts present within the synovium, showed
      significant labeling by transfected cells up to 6 days after intraarticular
      injection. Xenogeneic fibroblasts (Chinese hamster ovary cells) injected
      intraarticularly were also detected within synovial specimens; however, labeling
      intensity was less marked than with autologous cells. Our findings establish the
      feasibility of skin fibroblast grafting into the synovium. CONCLUSION: This
      preliminary study opens the door to studies of heterotopic autologous transfected
      cells for the treatment of CIA in monkeys by direct gene transfer within joints.

PMID- 17224294
TI  - Role for positron emission tomography in skeletal diseases.
AB  - Imaging plays a prominent role in the diagnosis and management of rheumatic
      diseases. Conventional imaging methods provide high-resolution structural
      information but usually fail to distinguish between active lesions and residual
      changes. Positron emission tomography (PET) with the tracer 18F
      fluorodeoxyglucose (18F-FDG) was recently introduced into clinical practice as a
      means of obtaining information on both structure and metabolic activity. 18F-FDG
      PET is widely used in oncology and may be valuable in patients with infections or
      inflammatory diseases, most notably vasculitis. Although encouraging results have
      been published, the number of studies remains small, as 18F-FDG-PET is an
      expensive investigation that is not available everywhere. Further work is needed
      to determine the cost-effectiveness ratio of 18F-FDG-PET in patients with
      infections or inflammatory diseases. Imaging plays a prominent role in the
      diagnosis and management of many musculoskeletal diseases. Although considerable
      progress has been made recently, the structural information supplied by
      conventional imaging methods is inadequate in some patients. Positron emission
      tomography (PET) after injection of 18fluorodeoxyglucose (18F-FDG) provides
      information on tissue metabolism. The usefulness of 18F-FDG-PET in oncology is
      now widely recognized. Other uses are emerging, in part thanks to the development
      of new cameras that combine dedicated detectors and an X-scanner in order to
      ensure accurate three-dimensional localization of metabolically active lesions.
      However, the exact role for 18F-FDG-PET needs to be studied in larger populations
      of patients.

PMID- 17224295
TI  - Electrosynthetic reduction of 1-iodoadamantane forming 1,1'-biadamantane and
      adamantane in aprotic solvents: insonation switches the mechanism from
      dimerisation to exclusive monomer formation.
AB  - The combination of ultrasound and electrochemistry -sonoelectrochemistry can
      produce a variety of effects within an electrochemical system including enhanced
      mass transport, in situ cleaning of an electrode surface, diminution of the
      diffusion layer, and possible induction of new reactions by sonochemical
      enhancement of follow-up reactions post-electron transfer. Herein, we show that
      ultrasound provides a useful extra dimension to electrosynthesis via a switch in
      the sonoelectroorganic mechanism in which dimerisation is disfavoured by virtue
      of convective mixing promoted by insonation. Under 'normal' voltammetric
      conditions the reduction of 1-iodoadamantane at a silver cathode in
      tetrahydrofuran (THF) and acetonitrile (ACN) involves a single electron forming a
      mixture of monomeric and dimeric products; 58%/THF, 50%/ACN adamantane and
      39%/THF, 50%/ACN 1,1'-biadamantane, respectively. However, under the conditions
      of insonation using a 10 kHz transducer, a single product is formed exclusively;
      93%/THF, 96%/ACN adamantane. The effect of insonation upon the voltammetry at a
      silver macroelectrode is shown and compared to that under silent conditions. In
      addition, the previously observed characteristic series of oxidation and
      adsorption peaks following reduction of 1-iodoadamantane are reduced in magnitude
      under insonation. Overall, this work shows that the effect of insonation can
      switch the mechanism of follow-up chemical processes - favoring the formation of
      a monomer.

PMID- 17224296
TI  - Investigation on the transition crystal of ordinary rutile TiO2 powder by
      microwave irradiation in hydrogen peroxide solution and its sonocatalytic
      activity.
AB  - The transition crystal TiO(2) catalyst with high sonocatalytic activity was
      obtained utilizing the microwave irradiation in hydrogen peroxide solution. At
      the same time a series of affecting factors (microwave irradiation time, heat
      treated time and heat-treated temperature) to prepare the TiO(2) catalyst on the
      sonocatalytic degradation of parathion were considered in this paper. The
      ultrasound of low power was used as an irradiation source to induce treated
      TiO(2) particles to perform catalytic activity. The results show that the
      sonocatalytic activity of the transition crystal TiO(2) powder is obviously
      higher than those of pure ordinary rutile and anatase TiO(2) powders. At last,
      the parathion in aqueous solution was degraded completely and became some simple
      inorganic ions such as NO(3)(-), PO(4)(3-), SO(4)(2-), etc. The degradation ratio
      of parathion in the presence of the transition crystal TiO(2) catalyst attains
      nearly 80% within 60 min ultrasonic irradiation, while corresponding ones are
      only 65.23% and 53.88%, respectively, for pure ordinary rutile and anatase TiO(2)
      powders.

PMID- 17224297
TI  - Mapping the efficacy of new designs for large scale sonochemical reactors.
AB  - Sonochemical reactors have a great promise for many physical and chemical
      processing applications but its applicability at pilot or industrial scale levels
      is hindered by lack of novel designs which can reproduce the spectacular effects
      generated at the laboratory scale. The present work evaluates the efficacy of two
      new designs, operating at a liquid capacity of 7l. Mapping of the cavitational
      activity has been carried out using measurements of local pressure using
      hydrophone and cativational intensity using Cavitation Activity Indicator (Model
      IC-3, N. Deznukov, Belarus State University, Minsk, Belarus). Aim has been to
      identify the distribution of the cavitational activity in radial and axial
      directions and possibly characterizing the zones with very high and very low
      cavitational activity in these reactor configurations. It has been observed that
      the cavitational activity is substantially uniform in both the reactors unlike
      the conventional single transducer based reactors. The study clearly indicates
      the feasibility of these designs for future large scale applications.

PMID- 17224299
TI  - Dealing with heterogeneity in clinical trials.

PMID- 17224298
TI  - Mechanism of the protective effects of long chain n-alkyl glucopyranosides
      against ultrasound-induced cytolysis of HL-60 cells.
AB  - Recently it has been shown that long chain (C5-C8) n-alkyl glucopyranosides
      completely inhibit ultrasound-induced cytolysis [J.Z. Sostaric, N. Miyoshi, P.
      Riesz, W.G. DeGraff, and J.B. Mitchell, Free Radical Biol. Med., 39 (2005) 1539].
      This protective effect has possible applications in HIFU (high intensity focused
      ultrasound) for tumor treatment, and in ultrasound assisted drug delivery and
      gene therapy. n-Alkyl glucopyranosides with hexyl (5mM), heptyl (3mM), octyl
      (2mM) n-alkyl chains protected 100% of HL-60 cells in vitro from 1.057 MHz
      ultrasound-induced cytolysis under a range of conditions that resulted in 35-100%
      cytolysis in the absence of glucopyranosides. However the hydrophilic methyl-beta
      d-glucopyranoside did not protect cells. The surface active n-alkyl
      glucopyranosides accumulate at the gas-liquid interface of cavitation bubbles.
      The OH radicals and H atoms formed in collapsing cavitation bubbles react by H
      atom abstraction from either the n-alkyl chain or the glucose moiety of the n
      alkyl glucopyranosides. Owing to the high concentration of the long chain
      surfactants at the gas-liquid interface of cavitation bubbles, the initially
      formed carbon radicals on the alkyl chains are transferred to the glucose
      moieties to yield radicals which react with oxygen leading to the formation of
      hydrogen peroxide. In this work, we find that the sonochemically produced
      hydrogen peroxide yields from oxygen-saturated solutions of long chain (hexyl,
      octyl) n-alkyl glucopyranosides at 614 kHz and 1.057 MHz ultrasound increase with
      increasing n-alkyl glucopyranoside concentration but are independent of
      concentration for methyl-beta-D-glucopyranoside. These results are consistent
      with the previously proposed mechanism of sonoprotection [J.Z. Sostaric, N.
      Miyoshi, P. Riesz, W.G. DeGraff, and J.B. Mitchell, Free Radical Biol. Med., 39
      (2005) 1539]. This sequence of events prevents sonodynamic cell killing by
      initiation of lipid peroxidation chain reactions in cellular membranes by peroxyl
      and/or alkoxyl radicals [V. Misik, P. Riesz, Ann. N.Y. Acad. Sci., 899 (2000)
      335].

PMID- 17224300
TI  - Capturing diversity in the cereals: many options but little promiscuity.
AB  - It is generally recognized by geneticists and plant breeders alike that there is
      a need to further improve the ability to capture and manipulate genetic
      diversity. The effective harnessing of diversity in traditional breeding
      programmes is limited and, therefore, it is vital that meiotic recombination can
      be manipulated given that it plays a pivotal role in generating diversity. With
      the advent of a wider range of genomics technologies, our understanding of
      meiotic processes should increase rapidly. Although comparative genetics has been
      useful, particularly in the broader grass family, the development of physical
      maps, long-range sequencing and transcript profiles promises to unravel the
      complexities of genomes as large or larger than wheat. Highlighting the most
      significant findings to date, this review pools the knowledge on these tools and
      reproductive processes.

PMID- 17224301
TI  - Transcriptional regulation in wood formation.
AB  - Wood (i.e. xylem tissue) in trees is mainly composed of two types of cells,
      fibres and tracheary elements. Recent molecular studies of various trees, as well
      as the non-tree species Arabidopsis thaliana and Zinnia elegans, have revealed
      coordinated gene expression during differentiation of these cells in wood and the
      presence of several transcription factors that might govern the complex networks
      of transcriptional regulation. This article reviews recent findings concerning
      the regulation of genes by transcription factors involved in wood formation such
      as AUXIN RESPONSE FACTOR (ARF), CLASS III HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIPIII),
      KANADI (KAN), MYB and NAM/ATAF/CUC (NAC).

PMID- 17224302
TI  - Methods for linkage disequilibrium mapping in crops.
AB  - Linkage disequilibrium (LD) mapping in plants detects and locates quantitative
      trait loci (QTL) by the strength of the correlation between a trait and a marker.
      It offers greater precision in QTL location than family-based linkage analysis
      and should therefore lead to more efficient marker-assisted selection, facilitate
      gene discovery and help to meet the challenge of connecting sequence diversity
      with heritable phenotypic differences. Unlike family-based linkage analysis, LD
      mapping does not require family or pedigree information and can be applied to a
      range of experimental and non-experimental populations. However, care must be
      taken during analysis to control for the increased rate of false positive results
      arising from population structure and variety interrelationships. In this review,
      we discuss how suitable the recently developed alternative methods of LD mapping
      are for crops.

PMID- 17224303
TI  - The guideline of the personal health data structure to secure safety healthcare.
      The balance between use and protection to satisfy the patients' needs.
AB  - PURPOSE: To inform about the impact of a recent movement towards a policy to
      develop integrative networked electronic health record (EHR) as a basis for
      cooperation among care teams and with patients and in support of safe patient
      care in Japan. METHODS: The author headed a commission developing policy for
      health record (HR) structure and its computerization. It executed two
      questionnaire surveys as the basis for its work. One survey assessed the current
      state of computerization of health record in the hospitals certified by Japan
      Council for Quality Health Care (JCQHC). The other survey assessed the attitudes
      towards a specific EHR system in the Hiroshima University Hospital and its
      affiliate hospitals. RESULTS: The survey of the above hospitals showed that most
      have computer supported administrative procedures, but only few computer-based
      health records. The attitudes of the Hiroshima EHR users show that while they
      expect efficiency and quality improvements, there is also apprehension that the
      system in use might lower practical efficiency and compromise patient safety.
      Accordingly, health recording requirements and storage policy have been
      restructured and communicated to the hospitals. CONCLUSION: These insights led to
      the initiation of curricula educating "Health Information Technologist" which is
      promoted by Japan Association Medical Informatics and the criterion of Chart
      Review Promotion of JCQHC. They will also lead to recommendation for improved and
      advanced EHR.

PMID- 17224304
TI  - Improved multiplex-PCR to identify hepatitis B virus genotypes A-F and
      subgenotypes B1, B2, C1 and C2.
AB  - BACKGROUND: There are eight genotypes (A-H) and numerous subgenotypes of
      hepatitis B virus (HBV). The genotype has been shown to affect the course of HBV
      infection. OBJECTIVES: To develop an efficient genotyping and subgenotyping
      method for large-scale epidemiological surveys of HBV infection in countries with
      high prevalence of HBV B and C such as China. STUDY DESIGN: We designed genotype
      and subgenotype-specific primer pairs, and adjusted PCR conditions for a
      multiplex-PCR using common Taq polymerase to identify HBV genotypes A-F in one
      reaction and for the main subgenotypes B1/B2 and C1/C2 in another reaction.
      RESULTS: We have developed a multiplex-PCR system, which specifically amplifies
      DNA of HBV genotypes and the corresponding main subgenotypes B and C from the
      sera of HBV patients. Our patients were infected with HBV of subgenotypes B2
      (n=18), C1 (n=2) and C2 (n=48). Eleven patients were doubly infected and three
      showed a triple infection with HBV A, B and C. CONCLUSIONS: The low-cost
      multiplex-PCR for identification of HBV genotypes A-F and main subgenotypes of
      HBV B and C, is rapid, reliable and sufficient for large-scale epidemiological
      surveys and clinical studies.

PMID- 17224305
TI  - Balance control in Sensory Neuron Disease.
AB  - OBJECTIVE: Balance control under static and dynamic conditions was assessed in
      patients with Sensory Neuron Disease (SND) in order to shed further light on the
      pathophysiology of ataxia. METHODS: Fourteen patients with diabetic
      polyneuropathy and 11 with SND underwent clinical and neurophysiological
      evaluation, stabilometric recording of body sway during quiet stance with and
      without vision, stereometric analysis of body segment displacement while riding a
      platform translating in anterior-posterior direction with and without vision
      (dynamic condition), and EMG recording of leg muscle responses to abrupt stance
      perturbation produced by rotation of a supporting platform. The findings were
      compared to those of age matched normal subjects. RESULTS: Clinical and
      neurophysiological evaluation revealed a more severe motor impairment in patients
      with diabetes than SND, while sensory impairment was superimposable. Some
      patients with SND had vestibular dysfunction of diverse severity. Body sway
      during stance was larger in patients with SND than diabetes with and without
      vision. In the stance perturbation condition, the latency of the long-loop EMG
      response to platform rotation was disproportionately increased with respect to
      the spinal response in the SND but not in diabetic patients. Under dynamic
      condition, patients with SND oscillated more than diabetic patients and several
      of them easily lost balance with eyes closed. CONCLUSIONS: Patients with SND show
      severe unsteadiness under both static and dynamic conditions, particularly with
      eyes closed. The patchy sensory loss of SND, disrupting sensation from
      territories other than the lower limbs and possibly including the vestibular
      nerve, could be responsible for this instability. Ataxia is correlated to the
      abnormal latency of the muscle responses to stance perturbation. Since increased
      response latencies cannot be attributed to a vestibular deficit, the
      deterioration of equilibrium control would be ascribed mainly to the degeneration
      of the central branch of the afferent fibres. SIGNIFICANCE: Measures of body
      balance under quiet stance and dynamic conditions can provide relevant diagnostic
      information as to the pathophysiology and severity of ataxia and viability of the
      central branch of the sensory fibres, and help in separating patients with
      peripheral neuropathy from patients with loss of sensory neurones.

PMID- 17224307
TI  - Therapeutic plasma exchange in the treatment of neuroimmunologic disorders:
      review of 50 cases.
AB  - Therapeutic plasma exchange (TPE) has been used for the treatment of neurologic
      diseases in which autoimmunity plays a major role. We reviewed the medical
      records of our patients who had consecutively been treated by TPE between January
      1998 and June 2000. Neurological indications included myasthenia gravis (30
      patients), multiple sclerosis attack (6 patients with remitting-relapsing course
      and 3 patients with secondary progressive course), Guillain-Barre syndrome (6
      patients), paraproteinemic neuropathy (2 patients), and chronic inflammatory
      demyelinating neuropathy (CIDP), transverse myelitis due to systemic lupus
      erythematosus, acute disseminated encephalomyelitis in one patient each.
      Continuous flow cell separators were used for TPE. TPE was generally given every
      other day for all of the patients and one plasma volume was exchanged for each
      cycle. Although the patients with secondary progressive multiple sclerosis (3
      patients) and paraproteinemic neuropathy (2 patients) did not show any
      improvement after TPE, other patients' targeted neurological deficits were
      improved by TPE. During the TPE procedures, no patient had any morbidity or
      mortality, and the complications were mild and manageable such as hypotension,
      hypocalcemia and mild anemia; three patients had septicemia due to the venous
      catheter used for TPE. TPE is an effective treatment in neurologic diseases in
      which autoimmunity plays an important role in pathogenesis, and it is safe when
      performed in experienced centers.

PMID- 17224306
TI  - Enterohaemorrhagic Escherichia coli O157 and non-O157 serovars differ in their
      mechanisms for iron supply.
AB  - Clinical isolates of enterohaemorrhagic Escherichia coli, both O157 and non-O157
      serotypes, were investigated for siderophore production, for growth promotion by
      haem and esculetin in iron-restricted conditions, for production of
      enterohaemolysin and esculin hydrolase, and for the presence of the chuA and ehx
      genes by PCR. As expected, all the strains produced enterobactin, but the
      prevalence of other factors varied among the serovars tested. None of the O157
      and O26 strains produced aerobactin or "colibactin", whereas among other
      enterohaemorrhagic E. coli non-O157 serovars the frequencies of aerobactin and
      "colibactin" production were similar to those of commensal E. coli strains. The
      ability to use ferric esculetin for growth in iron-limited media was markedly
      more prevalent among non-O157 serovars and less prevalent among O157 strains
      compared with commensal E. coli strains. Almost all O157, O26 and O103 strains
      expressed enterohaemolysin, compared with only 50% of other non-O157 strains.
      Similarly, almost all O157 and O26 strains utilised haem as a host iron source;
      the frequency of haem use by other non-O157 strains was generally lower and
      variable among serovars, such that none of the O103:H2 isolates tested used haem
      as an iron source. The gene chuA, which encodes the haem transport protein ChuA
      and which is prevalent in O157:H7 strains, was only rarely noted among non-O157
      serovars of enterohaemorrhagic E. coli, even among isolates that could use haem
      as an iron source. Overall our data demonstrate that O157:H7 and non-O157
      serovars, in particular O26:H(-)/H11 and O103:H2, use distinctly different
      strategies for obtaining iron, and suggest two evolutionary distinct lines of
      enterhaemorrhagic E. coli.

PMID- 17224308
TI  - A 6-month longitudinal study of bone mineral density with antiepileptic drug
      monotherapy.
AB  - Antiepileptic drugs (AEDs) can affect bone metabolism, but the exact mechanisms
      or differences in individual drugs are still unknown. The purpose of this study
      was to prospectively investigate the alterations in bone mineral density (BMD)
      and markers of bone metabolism induced by different AEDs in Koreans with
      epilepsy. Subjects included 33 drug-naive, newly diagnosed patients with epilepsy
      aged between 18 and 50. BMD at right calcaneus and various markers for bone
      metabolism were measured before and after 6months of AED monotherapy including
      carbamazepine, valproic acid, and lamotrigine. Carbamazepine caused a significant
      decrease in BMD, which was accompanied by a decrease in the level of vitamin D
      (25-OHD(3)). BMD and vitamin D were not affected by 6months of valproic acid or
      lamotrigine therapy. Interestingly, valproic acid and lamotrigine, but not
      carbamazepine, significantly increased osteocalcin, a marker of bone formation.
      All AEDs almost doubled the parathyroid hormone level, whereas urinary Pyrilinks,
      a marker of bone resorption, was not affected by those AEDs. These findings
      suggest that carbamazepine, a hepatic enzyme-inducing drug, decreases BMD.

PMID- 17224309
TI  - Apolipoprotein E polymorphism, age and coronary heart disease.
AB  - Plasma concentrations of lipids, lipoproteins, and apolipoproteins (apo) are
      established risk factors for coronary heart disease (CHD). The knowledge of lipid
      profile may predict the potential victims of cardiovascular disease before its
      initiation and progression and offer the opportunity for primary prevention. The
      most common apo E polymorphism has been found to influence blood lipid
      concentrations and its correlation with CHD has been extensively investigated in
      the last decade. At younger ages, death from CHD is influenced by genetic
      factors, while the genetic effect decreases at older ages where environmental
      factors may play a more prominent role. If apo E polymorphism is an important
      genetic factor in the pathogenesis of atherosclerosis, it could affect the age of
      CHD onset. This review analyses the influence of apo E polymorphism on blood
      lipids and CHD in respect to age.

PMID- 17224310
TI  - Determination of alginate copolymer in pharmaceutical formulations by micellar
      electrokinetic chromatography.
AB  - A micellar electrokinetic chromatography method was developed for the
      determination and quantification of sodium alginate. The alginate peak migrated
      in the very short time of 1.33 min and calibrated easily though the polydisperse
      properties of alginates. The minimum detection limit (LOD) of the method was
      calculated as 0.393 mg/ml. This analysis method was successfully applied to the
      alginate quantification in an antacid pharmaceutical formulation. Precise and
      reproducible analysis results were obtained, with liquid formulations injected
      directly without any pre-separation process.

PMID- 17224311
TI  - Scale-up of monoclonal antibody purification processes.
AB  - Mammalian cell culture technology has improved so rapidly over the last few years
      that it is now commonplace to produce multi-kilogram quantities of therapeutic
      monoclonal antibodies in a single batch. Purification processes need to be scaled
      up to match the improved upstream productivity. In this chapter key practical
      issues and approaches to the scale-up of monoclonal antibody purification
      processes are discussed. Specific purification operations are addressed including
      buffer preparation, chromatography column sizing, aggregate removal, filtration
      and volume handling with examples given.

PMID- 17224312
TI  - Simultaneous quantification of flavonoids and triterpenoids in licorice using
      HPLC.
AB  - Numerous bioactive compounds are present in licorice (Glycyrrhizae Radix),
      including flavonoids and triterpenoids. In this study, a reversed-phase high
      performance liquid chromatography (HPLC) method for simultaneous quantification
      of three flavonoids (liquiritin, liquiritigenin and isoliquiritigenin) and four
      triterpenoids (glycyrrhizin, 18alpha-glycyrrhetinic acid, 18beta-glycyrrhetinic
      acid and 18beta-glycyrrhetinic acid methyl ester) from licorice was developed,
      and further, to quantify these 7 compounds from 20 different licorice samples.
      Specifically, the reverse-phase HPLC was performed with a gradient mobile phase
      composed of 25 mM phosphate buffer (pH 2.5)-acetonitrile featuring gradient
      elution steps as follows: 0 min, 100:0; 10 min, 80:20; 50 min, 70:30; 73 min,
      50:50; 110 min, 50:50; 125 min, 20:80; 140 min, 20:80, and peaks were detected at
      254 nm. By using our technique, a rather good specificity was obtained regarding
      to the separation of these seven compounds. The regression coefficient for the
      linear equations for the seven compounds lay between 0.9978 and 0.9992. The
      limits of detection and quantification lay in the range of 0.044-0.084 and 0.13
      0.25 microg/ml, respectively. The relative recovery rates for the seven compounds
      lay between 96.63+/-2.43 and 103.55+/-2.77%. Coefficient variation for intra-day
      and inter-day precisions lay in the range of 0.20-1.84 and 0.28-1.86%,
      respectively. Based upon our validation results, this analytical technique is a
      convenient method to simultaneous quantify numerous bioactive compounds derived
      from licorice, featuring good quantification parameters, accuracy and precision.

PMID- 17224313
TI  - On the suitability of nanocrystalline ferrites as a magnetic carrier for drug
      delivery: functionalization, conjugation and drug release kinetics.
AB  - Superparamagnetic nickel ferrite nanoparticles functionalized with polyvinyl
      alcohol, polyethylene oxide and polymethacrylic acid (PMAA) polymers and
      subsequently conjugated with doxorubicin anti-cancer drug are studied for their
      use as a magnetic carrier for drug delivery. Fourier transform infrared
      spectroscopy enabled examination of the ability of the nanoparticles to be
      functionalized with polymers and conjugated with doxorubicin drug. The
      functionalized polymer-coated nanocrystalline nickel ferrites retain the magnetic
      characteristics of non-functionalized nanocrystalline nickel ferrites
      (superparamagnetism, absence of hysteresis, remanence and coercivity at room
      temperature), encouraging their application as a magnetic carrier for drug
      delivery. The PMAA-coated nanoferrites are demonstrated as being a potentially
      superior magnetically targeted drug carrier based on FTIR results and drug
      release kinetics in the absence and presence of an external magnetic field.

PMID- 17224314
TI  - Modeling wear of cast Ti alloys.
AB  - The wear behavior of Ti-based alloys was analyzed by considering the elastic
      plastic fracture of individual alloys in response to the relevant contact stress
      field. Using the contact stresses as the process driving force, wear was computed
      as the wear rate or volume loss as a function of hardness and tensile ductility
      for Ti-based cast alloys containing an alpha, alpha+beta or beta microstructure
      with or without the intermetallic precipitates. Model predictions indicated that
      wear of Ti alloys increases with increasing hardness but with decreasing fracture
      toughness or tensile ductility. The theoretical results are compared with
      experimental data to elucidate the roles of microstructure in wear and contrasted
      against those in grindability.

PMID- 17224318
TI  - Tuberculous lymphadenitis.

PMID- 17224319
TI  - Pleural tuberculosis.

PMID- 17224320
TI  - Miliary, central nervous system, and genitourinary tuberculosis.

PMID- 17224321
TI  - Abdominal tuberculosis.

PMID- 17224322
TI  - Musculoskeletal tuberculosis.

PMID- 17224323
TI  - Tuberculosis of pericardium, larynx, and other uncommon sites.

PMID- 17224324
TI  - Tuberculosis and infection control measures.

PMID- 17224325
TI  - New drugs and vaccines.

PMID- 17224326
TI  - Key role of insulin resistance in vascular injury among hemodialysis patients.
AB  - Insulin resistance prevails not only among diabetic patients but also among
      hypertensive and obese patients. The relationship between insulin resistance and
      cardiovascular diseases was investigated in hemodialysis (HD) patients. Eighty
      one maintenance HD patients were enrolled. The homeostasis model assessment of
      insulin resistance (HOMA-IR) method was used to assess insulin resistance. The
      relationship of HOMA-IR with cardiovascular and all-cause events was assessed.
      Compared with nondiabetic patients (n = 55), diabetic patients (n = 26) showed
      higher HOMA-IR (2.5 +/- 0.3 vs 1.4 +/- 0.2, P < .05), lower ankle-brachial
      pressure index (ABI, 0.85 +/- 0.09 vs 1.12 +/- 0.02, P < .01), and shorter HD
      duration (3 +/- 1 vs 9 +/- 1 years, P < .01), although their body mass index was
      similar (22.3 +/- 0.5 vs 21.5 +/- 0.4 kg/m(2)). Nondiabetic patients taking
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (n =
      36) had lower HOMA-IR (1.2 +/- 0.2 vs 1.8 +/- 0.4, P < .05) and higher ABI (1.18
      +/- 0.02 vs 1.02 +/- 0.05, P < .01) than those without (n = 17). Cardiovascular
      events were less common in HD patients with normal HOMA-IR (P < .05) or ABI (P <
      .01). Our data indicate that 69% of diabetic and 27% of nondiabetic patients have
      HOMA-IR greater than 1.6, implying reduced insulin sensitivity in HD patients.
      The present results provide evidence that angiotensin inhibition improves insulin
      resistance, possibly preventing vascular injury in HD patients. Finally, our
      findings suggest that insulin resistance is prognostic of cardiovascular events
      in HD patients.

PMID- 17224327
TI  - Effect of pyridoxamine (K-163), an inhibitor of advanced glycation end products,
      on type 2 diabetic nephropathy in KK-A(y)/Ta mice.
AB  - Advanced glycation end products (AGEs) from the Maillard reaction contribute to
      the pathogenesis of diabetes-associated complications such as diabetic
      nephropathy. In therapeutic interventions for reducing AGEs, many compounds have
      been reported as AGE inhibitors. The objective of the present study was to
      examine the effect of pyridoxamine (K-163), an AGE inhibitor, in type 2 diabetic
      KK-A(y)/Ta mice. KK-A(y)/Ta mice were given pyridoxamine (200 or 400 mg/kg per
      day) starting at 8 weeks of age for 12 weeks. They were divided into 3 groups as
      follows: pyridoxamine 200 mg/kg per day treatment group (n = 10), pyridoxamine
      400 mg/kg per day treatment group (n = 10), and a tap water group as the control
      group (n = 20). The urinary albumin/creatinine ratio (ACR), body weight (BW),
      levels of fasting and casual blood glucose, blood glycated hemoglobin (HbA(1c)),
      fasting serum insulin, triglyceride (TG), total cholesterol (T-Cho), and 3
      deoxyglucosone (3DG), and systemic blood pressure were measured as biochemical
      parameters. N(epsilon)-(Carboxymethyl)lysine (CML) and nitrotyrosine
      accumulations in glomeruli were evaluated by immunohistochemical analyses.
      Transforming growth factor beta1 (TGF-beta1) and laminin-beta1 messenger RNA
      expressions in the kidneys were evaluated by real-time polymerase chain reaction.
      Pyridoxamine, especially at 400 mg/kg per day, improved the levels of urinary
      ACR, fasting serum TG, and 3DG. CML and nitrotyrosine accumulations in glomeruli
      were decreased. Furthermore, large doses of pyridoxamine prevented not only
      urinary ACR but also increases of BW, casual blood glucose, and HbA(1c). TGF
      beta1 and laminin-beta1 messenger RNA expressions in kidneys were significantly
      lower than those in the controls. There were no significant changes in the levels
      of fasting blood glucose, serum T-Cho, and systemic blood pressure among all
      groups. It appears that pyridoxamine improved urinary ACR by its anti-AGE and
      anti-oxidant effects in the kidneys of KK-A(y)/Ta mice.

PMID- 17224328
TI  - Vitamin B6 (pyridoxamine) supplementation and complications of diabetes.

PMID- 17224329
TI  - Admissions for diabetic ketoacidosis in ethnic minority groups in a city
      hospital.
AB  - Hospitalization for diabetic ketoacidosis (DKA) is increasing, perhaps due to the
      rising incidence of DKA in patients with type 2 diabetes mellitus (T2DM). Ethnic
      minority groups are at increased risk for T2DM. This study aimed at elucidating
      the characteristics of patients with ketosis-prone diabetes in a predominantly
      ethnic minority population. We performed a retrospective analysis of adults
      admitted with DKA at the Bronx Lebanon Hospital Center, Bronx, NY over 3 years.
      The patients were divided into cohorts based on type of diabetes and ethnicity.
      The cohorts were described and compared using statistical methods. We recorded
      219 cases of DKA in 168 patients, 97% of whom were African American or Hispanic.
      Fifty-three (32%) patients had T2DM. New-onset diabetes, which was more common in
      T2DM (P < .0001), and African Americans (P = .008), occurred in 42 patients
      (25%). Readmission with DKA was more common in the Hispanic patients with type 1
      diabetes mellitus (T1DM) (P = .0001). Type 2 diabetes mellitus was more prevalent
      in the African Americans (P = .04). Patients with T1DM had more severe acidosis
      than patients with T2DM (lower pH and bicarbonate and larger anion gap; P = .03,
      .02, and .005, respectively). Creatinine level was higher in patients with T2DM
      (P = .04) who were also less likely to have identifiable precipitating causes (P
      = .02). Hemoglobin A(1c) level was higher in patients with new-onset diabetes (P
      < .05), but did not differ between those with T1DM and T2DM. Mortality, which was
      2%, occurred only in the African Americans with T2DM. We conclude that DKA is an
      important mode of initial presentation of T2DM, with new-onset T2DM accounting
      for about 60% of all new cases of DKA. African American patients with T2DM, in
      comparison with the Hispanic patients, are more susceptible to developing DKA.
      Diabetic ketoacidosis could occur in T2DM without any identifiable precipitant.
      The rising incidence of DKA may be attributable to its increasing occurrence in
      T2DM; therefore, measures aimed at primary prevention of T2DM are worthwhile.

PMID- 17224330
TI  - Smoking is associated with urinary albumin excretion: an evaluation of
      premenopausal patients with type 2 diabetes mellitus.
AB  - Cigarette smoking and an increase in urinary albumin excretion are associated
      with high mortality in patients with type 2 diabetes mellitus. We tested the
      hypothesis that the presence of a smoking habit correlates with increased urinary
      albumin excretion in premenopausal Japanese women with type 2 diabetes mellitus.
      The study consisted of 20 premenopausal Japanese patients with type 2 diabetes
      mellitus in the current-smokers group (age, 45 +/- 4 years, mean +/- SD). The
      control group consisted of 35 age-matched never-smoker patients (age, 45 +/- 5
      years). Serum triglyceride levels were higher and high-density lipoprotein
      cholesterol levels were lower in the current-smokers group than in the never
      smokers group (P < .05 and P < .01, respectively). Furthermore, fasting plasma
      insulin concentrations and the homeostasis model assessment index were higher in
      the current-smokers group than in the never-smokers group (P < .005 and P < .001,
      respectively). Urinary albumin excretion also was higher in the current-smokers
      group than in the never-smokers group (P < .0001). Multivariate logistic analysis
      revealed that urinary albumin excretion is independently associated with current
      smoking in Japanese premenopausal with type 2 diabetes mellitus (odds ratio,
      1.79; 95% confidence interval, 1.08-3.87; P < .01). The results of this study
      show that current smoking is associated with an increased level of urinary
      albumin excretion, suggesting that smoking was a risk factor in the development
      of increased urinary albumin excretion in these patients.

PMID- 17224331
TI  - Long-term oral lysine supplementation in lysinuric protein intolerance.
AB  - In lysinuric protein intolerance (LPI), defective transport of cationic amino
      acids at the basolateral membrane of the polar epithelial cells in the intestine
      and renal tubules leads to decreased intestinal absorption and excessive renal
      loss of lysine, arginine, and ornithine. Citrulline supplementation partially
      restores the function of the urea cycle that is impaired by deficiency of
      arginine and ornithine, but does not correct the chronic lysine deficiency.
      Previous attempts to supplement lysine orally have been hindered by profuse
      diarrhea, probably caused by excess lysine remaining unabsorbed in the gut.
      However, individually adjusted minute doses of L-lysine hydrochloride at
      mealtimes are tolerated well, but the long-term benefits of this therapy remain
      unknown. The aim of the study was to investigate the long-term benefits and
      possible adverse effects of oral lysine supplementation in patients with LPI.
      Supplementation of meals with low doses of oral lysine improved fasting plasma
      lysine concentrations in 27 Finnish patients with LPI without causing
      hyperammonemia or other recognizable side effects during 12 months of follow-up.
      In conclusion, low-dose oral lysine supplementation is potentially beneficial to
      patients with LPI and can be started safely at an early age.

PMID- 17224332
TI  - Insulin resistance induced by high glucose and high insulin precedes insulin
      receptor substrate 1 protein depletion in human adipocytes.
AB  - The aim of this study was to investigate whether high glucose and/or high insulin
      produces cellular insulin resistance in human adipocytes and, if so, to evaluate
      the time course and content of key proteins in the insulin signaling pathway.
      Subcutaneous fat biopsies were taken from 27 nondiabetic subjects. Insulin action
      in vitro was studied by measurement of glucose uptake after incubation at a
      physiologic glucose level (6 mmol/L) for 24 hours or with the last 2, 6, or 24
      hours at a high glucose level (20 mmol/L) with or without high insulin
      (10(4)microU/mL). High glucose alone for 24 hours produced a small but
      significant impairment (by approximately 20%, P < .05) of insulin's effect to
      stimulate glucose transport, whereas nonstimulated glucose uptake was left
      intact. In contrast, the combination of high glucose and high insulin for 6 hours
      or more reduced basal glucose uptake by approximately 40% (P < .05). In addition,
      insulin-stimulated glucose uptake capacity was reduced by approximately 40%
      already after 2 hours (P < .05) and reached a maximal decline (by approximately
      50%, P < .05) after a 6-hour culture in high glucose and high insulin. Treatment
      with high glucose and high insulin in combination for at least 6 hours reduced
      cellular insulin receptor substrate (IRS)-1, but not IRS-2, protein content by
      approximately 45% or more (P < .05). Moreover, after 24 hours, the ability of
      insulin to activate protein kinase B (ie, the phosphorylated protein kinase B
      [pPKB]-protein kinase B ratio) was decreased by approximately 50% (P < .05). No
      significant effects were seen on insulin signaling proteins or glucose
      transporter 4 after a long-term high-glucose culture. Culture with high insulin
      alone (and low glucose, 6 mmol/L) decreased basal and insulin-stimulated glucose
      uptake in conformity with the high-glucose/high-insulin setting. However, IRS-1
      protein content remained unchanged. We conclude that, in adipocytes from healthy
      humans, high insulin alone for 2 hours or more decrease glucose uptake capacity.
      Likewise, high glucose and high insulin in combination for 2 hours or more
      decrease glucose uptake to the same extent as when cells were cultured with high
      insulin alone but, in addition, with a diminishment in IRS-1 protein lagging
      behind. Thus, IRS-1 depletion appears to be a secondary phenomenon in this model
      of insulin resistance. High glucose alone induces only a minor insulin resistance
      in human fat cells.

PMID- 17224333
TI  - Association of the Gly82Ser polymorphism in the receptor for advanced glycation
      end products (RAGE) gene with circulating levels of soluble RAGE and inflammatory
      markers in nondiabetic and nonobese Koreans.
AB  - We investigated the association between the Gly82Ser (G82S) polymorphism in the
      receptor for advanced glycation end products (RAGE) gene and circulating levels
      of soluble RAGE (sRAGE), advanced glycation end products (AGEs), and inflammatory
      markers in nondiabetic/nonobese Koreans. A total of 1096 men and 580 women aged
      30 to 69 years and with body mass index of 18.5 to 29.9 kg/m(2) were recruited.
      Anthropometrics, lipid profiles, glucose, insulin, insulin resistance (IR), RAGE
      G82S polymorphism, sRAGE, AGEs, and inflammatory markers were measured. There was
      a significant association between G82S genotypes and plasma sRAGE concentrations
      (P < .001). sRAGE concentrations were significantly higher in subjects with the
      G/G genotype (1038 +/- 33 pg/mL) than in those with the G/S (809 +/- 19 pg/mL) or
      the S/S (428 +/- 43 pg/mL) genotype. Furthermore, the G82S genotypes in the RAGE
      gene were associated with serum AGE (P = .033), homeostasis model assessment for
      insulin resistance (HOMA-IR) (P < .001), plasma tumor necrosis factor alpha (TNF
      alpha) (P = .033), serum C-reactive protein (CRP) (P= .002), and urinary
      excretion of 8-epi-prostaglandin F(2alpha) (P = .028) after adjusting for sex,
      age, body mass index, cigarette smoking, and alcohol drinking. Subjects with the
      S/S genotype showed higher levels of serum AGE, HOMA-IR, plasma TNF-alpha, serum
      CRP, and 8-epi-prostaglandin F(2alpha) than those with the G/G or G/S
      combination. The sRAGE levels showed a negative relation with high-sensitivity
      CRP (r = -0.250; P < .001). The AGE concentrations showed a positive relation
      with TNF-alpha levels (r = 0.398; P < .001). Subjects with homozygosity for the
      minor S allele (S/S) of the G82S polymorphism had higher risk factors for
      cardiovascular disease, such as low sRAGE levels, inflammation, oxidative stress,
      and IR, compared with those bearing at least one G allele.

PMID- 17224334
TI  - Elevated total and central adiposity and low physical activity are associated
      with insulin resistance in children.
AB  - The aim of this study was 2-fold: (1) to examine insulin resistance, blood lipid
      levels, and inflammatory markers in 9- to 11.5-year-old obese and lean children
      and (2) to identify factors that influence insulin resistance in this cohort of
      youths. Body mass index, skinfold thickness, waist circumference, physical
      activity (4-day triaxial accelerometer), cardiorespiratory fitness (submaximal
      bicycle ergometer test), and dietary intake (3-day food records) were evaluated
      in 27 obese and 27 lean boys and girls. Fasting blood samples were analyzed for
      insulin, glucose, lipids and lipoproteins, C-reactive protein (CRP), interleukin
      6, soluble intercellular adhesion molecule, and soluble vascular cell adhesion
      molecule. Homeostasis model assessment (HOMA) was used to evaluate insulin
      resistance (HOMA-IR). Obese children presented higher HOMA-IR, CRP, and blood
      lipid levels (all P < .01) compared with lean children. Total body fat and waist
      circumference were positively associated with fasting insulin (r > or = 0.51),
      HOMA-IR (r > or = 0.56), CRP (r > or = 0.51), and blood triacylglycerol (r > or =
      0.38), and were inversely correlated with high-density lipoprotein cholesterol (r
      > or = -0.39; all P < .01). Cardiorespiratory fitness was inversely associated
      with HOMA-IR (r = -0.24; P < .05), but this association disappeared when adjusted
      for age, sex, and fat mass. Waist circumference and total daily physical activity
      explained 49% of the variance in HOMA-IR in these children. In conclusion, these
      findings suggest that total and central adiposity are positively associated and
      physical activity is negatively associated with insulin resistance in children.
      Interventions to improve glucose metabolism in youth should target at reducing
      total body and abdominal fat and increasing physical activity. The lack of
      association between inflammatory markers and HOMA-IR suggests that obesity may
      precede the elevation of these markers in the evolution of insulin resistance in
      youth.

PMID- 17224335
TI  - The effects of hypothermia on fibrinogen metabolism and coagulation function in
      swine.
AB  - Clinical coagulopathy frequently occurs in the presence of hypothermia. The
      primary purpose of this study was to investigate the effects of hypothermia on
      clotting protein fibrinogen metabolism and on coagulation function in a swine
      model. Twelve pigs were randomly allocated into control and hypothermia groups.
      Hypothermia of 32 degrees C was induced using a blanket with circulating water at
      4 degrees C. Fibrinogen synthesis and breakdown were quantified using a 6-hour
      stable isotope infusion with subsequent gas chromatograph and mass spectrometry
      analysis. Clotting enzyme thrombin generation kinetics was quantified at baseline
      and at the end of the infusion. Changes in fibrinogen metabolism and thrombin
      generation were correlated with coagulation function assessed by
      thromboelastography (TEG). Hypothermia decreased fibrinogen synthesis from the
      control value of 2.6 +/- 0.4 to 1.2 +/- 0.2 mg kg(-1) h(-1) (P < .05), with no
      effect on fibrinogen breakdown. Thrombin generation at the initiation phase was
      delayed by hypothermia, but there were no changes at the propagation phase. In
      thromboelastography measurements, the initial clotting time (R time) was
      prolonged from the baseline value of 3.01 +/- 0.13 to 4.30 +/- 0.24 minutes (P <
      .05) and clotting rapidity (angle alpha) was decreased from the baseline value of
      72.30 +/- 0.90 to 65.34 +/- 1.07 (P < .05). Hypothermia caused no significant
      changes in clot strength (maximum amplitude) and clot lysis (LY(60)). We
      concluded that hypothermia caused a potential deficit in fibrinogen availability
      and a delay in thrombin generation, consequently inhibiting coagulation function.
      Our data support the current practices of rewarming and prescribing recombinant
      factor VIIa for hypothermic patients with coagulation defects.

PMID- 17224336
TI  - High anticipatory stress plasma cortisol levels and sensitivity to
      glucocorticoids predict severity of coronary artery disease in subjects
      undergoing coronary angiography.
AB  - Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and/or increased
      sensitivity of peripheral tissues to glucocorticoids may be associated with the
      dysmetabolic syndrome and its cardiovascular sequelae. In this prospective pilot
      clinical study, we examined possible associations between HPA axis activity and
      severity of cardiovascular disease. We measured morning serum cortisol and intima
      media thickness (IMT) of carotid and femoral arteries in 105 subjects before
      undergoing coronary angiography for suspected coronary artery disease (CAD). In a
      randomly selected 46 of these subjects, we obtained late afternoon and morning
      cortisol levels (after ultralow-dose dexamethasone [0.25 mg] treatment) and
      determined their genotype for the Bcl1 polymorphism of the glucocorticoid
      receptor gene, which has been associated with increased sensitivity to
      glucocorticoids. There was significant association between morning preangiography
      cortisol levels and the number of vessels with severe stenosis in the
      angiography, independently of age or sex (P = .002), and a trend for a positive
      correlation between morning cortisol and the IMT of the femoral artery (P =
      .057). Bcl1 G allele homozygotes had a significantly higher carotid IMT (P =
      .005) and a nonsignificant tendency for higher waist-hip ratio (P = .059).
      Hyperactivity of the HPA axis in anticipation of a stressful procedure, such as
      angiography, may be an index of CAD severity. Chronic HPA axis hyperreactivity
      combined with tissue hypersensitivity to glucocorticoids may contribute to more
      severe atherosclerosis and CAD.

PMID- 17224337
TI  - Hepatic parasympathetic role in insulin resistance on an animal model of
      hypertension.
AB  - The hepatic insulin sensitizing substance (HISS) pathway, which includes the
      hepatic parasympathetic nerves and hepatic nitric oxide (HNO), has been shown to
      be crucial to the action of insulin on glucose metabolism. Insulin resistance in
      essential hypertension has been related to parasympathetic dysfunction; thus, we
      tested the hypothesis that the HISS pathway is impaired in spontaneously
      hypertensive rats (SHR) when compared with their normotensive controls, Wistar
      (WIS) and Wistar Kyoto (WKY) rats. A modified euglycemic clamp quantified insulin
      sensitivity. Differentiation of the HISS-dependent and HISS-independent
      components of insulin action was achieved by administration of a muscarinic
      receptor antagonist (atropine, 3 mg/kg) or of a nitric oxide synthase inhibitor
      (N(g)-methyl-arginine, 0.73 mg/kg). Both SHR and WKY had lower postprandial total
      insulin action when compared with WIS (209.1 +/- 13.6 for WKY and 217.8 +/- 19.8
      for SHR vs 296.1 +/- 16.9 mg glucose/kg body weight for WIS, P < .05).
      Furthermore, we observed that this is due to a decrease of the HISS-dependent
      component of insulin action (154.8 +/- 16.4 for WIS vs 87.1 +/- 14.5 for WKY and
      55.9 +/- 15.6 mg glucose/kg body weight for SHR; P < .05 and P < .001,
      respectively; data concerning the atropine protocol). Blockade of HISS action by
      inhibition of hepatic nitric oxide synthase with N(g)-methyl-arginine showed
      similar results to those obtained with atropine, suggesting that they indeed act
      through the same pathway. In conclusion, our results support our hypothesis that
      impairment of the HISS pathway is responsible for the development of insulin
      resistance between WIS and SHR.

PMID- 17224338
TI  - Genetic determination of adiponectin and its relationship with body fat
      topography in multigenerational families of African heritage.
AB  - Adiponectin, an adipose-specific protein, is negatively associated with
      adiposity, insulin sensitivity, and diabetes. Very few studies have examined the
      role of heredity in the regulation of adiponectin and its association with body
      fat among individuals of African heritage. Thus, we measured fasting serum
      adiponectin levels by radioimmunoassay and body composition by dual-energy x-ray
      absorptiometry (DEXA) in 402 individuals aged 18 to 103 years belonging to 7
      multigenerational families of African heritage in the relatively homogeneous
      island population of Tobago. Heritability of adiponectin was 33.2% (P < .01), and
      age, sex, and body mass index explained 23.4% of the variance in adiponectin. Sex
      specific heritability was significant in men (heritability, 34%; P < .05), but
      not in women. The inverse associations between body mass index and percentage of
      body fat and adiponectin, independent of age and height, were much stronger in
      women (all P values <.001) than in men. However, percentage of trunk fat was
      consistently strongly associated with adiponectin in both men (r = -0.40, P <
      .001) and women (r = -0.44, P < .001), independent of age and height. This study
      suggests that genetic factors are a significant source of interindividual
      differences in circulating adiponectin among Afro-Caribbeans. Adiponectin may
      serve as a promising quantitative intermediate trait in studies designed to map
      the genes underlying diabetes and obesity in this population.

PMID- 17224339
TI  - Frequency and outcome of patients with nonthyroidal illness syndrome in a medical
      intensive care unit.
AB  - Acute and chronic critical conditions are associated with reduced serum levels of
      free triiodothyronine (FT(3)), free thyroxine FT(4), and thyrotropin, known as
      nonthyroidal illness syndrome (NTIS). It is still controversial whether these
      changes reflect a protective mechanism or a maladaptive process during prolonged
      illness. However, larger studies to determine the prevalence of the NTIS and its
      association with outcome in medical intensive care units (ICUs) are missing.
      Complete thyroid hormone levels from 247 of 743 patients admitted to our ICU
      between October 2002 and February 2004 were retrospectively evaluated. From these
      patients, Acute Physiology and Chronic Health II scores, ICU mortality, length of
      stay, mechanical ventilation, and concomitant medication were recorded. Ninety
      seven patients (44.1%) had low FT(3) levels indicating an NTIS, either with
      normal (23.6%) or reduced (20.5%) serum thyrotropin levels. Of 97 patients with
      NTIS, 24 (23.3%) also showed reduced serum FT(4) levels. The NTIS was
      significantly associated with Acute Physiology and Chronic Health II scores,
      mortality, length of stay, and mechanical ventilation. In a multivariate Cox
      regression analysis, the combination of low FT(3) and low FT(4) was an
      independent risk factor for survival. Nonthyroidal illness syndrome is frequent
      at a medical ICU. A reduction of FT(4) together with FT(3) is associated with an
      increase in mortality and might reflect a maladaptive process, thereby worsening
      the disease.

PMID- 17224340
TI  - Oxidized low-density lipoprotein and intimal medial thickness in subjects with
      glucose intolerance: the Chennai Urban Rural Epidemiology Study-25.
AB  - The aim of the present study was to assess the association of oxidized low
      density lipoprotein (OX-LDL) with carotid intimal medial thickness (IMT) in
      different grades of glucose intolerance in Asian Indians. Three groups were
      recruited from the Chennai Urban Rural Epidemiology Study, a population-based
      study: group 1, normal glucose tolerance (NGT) (n = 175); group 2, impaired
      glucose tolerance (IGT) (n = 175); and group 3, type 2 diabetes mellitus (n =
      175). Oxidized LDL (enzyme-linked immunosorbent assay) and carotid IMT (high
      resolution B-mode ultrasonography) were assessed. Subjects with diabetes had
      higher IMT values (0.85 +/- 0.30 mm) compared with those who have IGT (0.79 +/-
      0.16 mm, P < .05) and NGT (0.71 +/- 0.12 mm, P < .001). Subjects with diabetes
      (40.1 +/- 13.1 U/L) and IGT (34.3 +/- 12.8 U/L) had significantly higher mean OX
      LDL values compared with the NGT group (26.2 +/- 16.6 U/L, P < .001). Oxidized
      LDL showed a correlation with IMT (total population: r = 0.294, P < .001;
      subjects with NGT: r = 0.444, P < .001; and subjects with IGT: r = 0.481, P <
      .001). In multiple linear regression analysis, OX-LDL showed a strong association
      with IMT (beta = .005, P < .001), even after adjusting for age, sex (beta = .003,
      P < .001), and glucose intolerance (beta = .002, P < .001). In conclusion, OX-LDL
      levels increase with increasing glucose intolerance. Oxidized LDL is associated
      with carotid IMT and this is independent of age, sex, and glucose intolerance
      status.

PMID- 17224341
TI  - Reverse cholesterol transport is regulated by varying fatty acyl chain saturation
      and sphingomyelin content in reconstituted high-density lipoproteins.
AB  - Because phospholipid composition of high-density lipoprotein (HDL) plays a vital
      role in its reverse cholesterol transport (RCT) function, we studied RCT in vitro
      (uptake and efflux) with reconstituted HDLs (rHDLs) containing
      phosphatidylcholine (PC) with fatty acids of increasing saturation levels
      (stearic, oleic, linoleic, linolenic) and without or with sphingomyelin (SM).
      Uptake significantly increased from basal value when the PC component included up
      to 50 mol % of oleic or linolenic acid, but did not change with linoleic acid.
      Increasing oleic and linoleic acids to 100 mol % significantly decreased uptake,
      but increasing linolenic acid to the same value did not affect it. Sphingomyelin
      in rHDL significantly decreased uptake, but only with PC-containing unsaturated
      fatty acids, and not with saturated fatty acid. Efflux was not affected in a dose
      dependent manner when oleic or linoleic acid content was increased, but was
      significantly increased with levels of linolenic acid up to 25 mol % in PC, and
      was dramatically lowered with higher levels. Sphingomyelin in rHDL (PC/SM, 20:80,
      mol/mol) significantly increased efflux only with oleic or linoleic acid
      containing rHDLs, compared with efflux without SM. In conclusion, enrichment of
      PC component up to 25 mol % as linolenic acid has a beneficial effect on RCT,
      whereas a higher percentage of it or other unsaturated fatty acids seems to be
      detrimental. In addition, high SM content decreases uptake with rHDL-containing
      unsaturated fatty acids, whereas it increases efflux for rHDL-containing oleic or
      linoleic acid. These results show for the first time the importance of SM in RCT
      in a well-defined in vitro system.

PMID- 17224342
TI  - Do novel risk factors differ between men and women aged 18 to 39 years with a
      high risk of coronary heart disease?
AB  - This study aimed to clarify whether high-risk premenopausal women have less
      atherogenic levels of markers of endothelial dysfunction, oxidation, thrombosis
      and inflammation, and adipokines than high-risk men of the same age. Thus, we
      studied levels of these markers and their determinants in 207 men and women aged
      18 to 39 years with dyslipidemia and a family history of premature coronary heart
      disease. Women had favorable levels of E and P selectins, tumor necrosis factor
      alpha, tissue plasminogen activator, plasminogen activator inhibitor 1,
      thrombomodulin, thiobarbituric acid reactive substances, and adiponectin compared
      with men, but had higher levels of high-sensitivity C-reactive protein and leptin
      (all P < .05) and no difference in the L-arginine/asymmetric dimethyl arginine
      (ADMA) ratio. This ratio was higher among nonusers of hormonal contraception than
      among users (P = .02). In multivariate analyses, levels of intercellular adhesion
      molecule 1 and E selectin were associated with cigarette smoking and dietary
      sucrose (both P < .05), whereas the L-arginine/ADMA ratio was paradoxically
      associated with smoking (P < .05). Of 17 novel risk markers, 11 were associated
      with body mass index after adjustment for age, sex, smoking, and percentage of
      dietary energy from sucrose (regression coefficients, 0.14-0.62; all P < .05). In
      conclusion, the findings underscore the female advantage regarding determinants
      of novel risk markers in young adults at risk of coronary heart disease, although
      some endothelial dysfunction markers (cellular adhesion molecules, L
      arginine/ADMA ratio) were not more favorable in women compared with men.
      Lifestyle factors including body mass index, dietary sucrose, smoking, and
      hormones were associated with levels of the markers independent of sex with body
      mass index being the most prominent factor.

PMID- 17224344
TI  - Soy compared to casein meal replacement shakes with energy-restricted diets for
      obese women: randomized controlled trial.
AB  - Recent studies suggest that obese individuals lose weight more rapidly and lose
      more total weight with soy protein than with animal protein as a major diet
      component. The purpose of the present study was to evaluate the weight-loss
      efficacy and changes in body composition, waist circumference, blood pressure,
      and levels of plasma glucose, insulin, serum lipids, C-reactive protein, and
      homocysteine from consumption of either 3 soy shakes or 3 casein shakes daily as
      part of a 16-week, energy-restricted diet for obese women. Forty-three women with
      body mass index values of 30 to 40 kg/m(2) were randomized to intensive dietary
      interventions using either casein (n = 21) or soy (n = 22) shakes. Subjects were
      instructed to consume 3 shakes, 1 prepackaged entree, and 5 servings of fruits or
      vegetables daily to achieve an energy intake of 4.5 to 5.0 MJ/d. Subjects
      attended classes weekly or biweekly. Weight, body fat, lipid, and glucose
      measurements were obtained at baseline and at 8 and 16 weeks. For both groups
      combined, subjects lost 8.1% of initial body weight (7.7 kg) at 8 weeks and 13.4%
      (12.7 kg) at 16 weeks. Weight loss from baseline did not differ significantly by
      group and, for completing subjects, was 14.0% +/- 1.2% (mean +/- SE) for casein
      and 12.8% +/- 1.4% for soy. With the intention-to-treat analysis, weight losses
      at 16 weeks were 12.5% +/- 1.4% for casein and 11.3% +/- 1.2% for soy. Body fat
      losses were 23.7% +/- 2.0% for casein and 21.8% +/- 2.4% for soy and did not
      differ significantly. Both study groups lost significant amounts of weight with a
      highly structured behavioral program incorporating 4 meal replacements and
      vegetables and fruits. Differences in weight loss and body composition changes
      between casein and soy treatments were not significant.

PMID- 17224343
TI  - Tumor necrosis factor and interleukin 1 decrease RXRalpha, PPARalpha, PPARgamma,
      LXRalpha, and the coactivators SRC-1, PGC-1alpha, and PGC-1beta in liver cells.
AB  - During the acute phase response, cytokines induce marked alterations in lipid
      metabolism including an increase in serum triglyceride levels and a decrease in
      hepatic fatty acid oxidation, in bile acid synthesis, and in high-density
      lipoprotein levels. Here we demonstrate that tumor necrosis factor (TNF) and
      interleukin 1 (IL-1), but not IL-6, decrease the expression of retinoid X
      receptor alpha (RXRalpha), peroxisome proliferator-activated receptor alpha
      (PPARalpha), PPARgamma, liver X receptor alpha (LXRalpha), and coactivators
      PPARgamma coactivator 1alpha (PGC-1alpha), PGC-1beta, and steroid receptor
      coactivator 1 (SRC-1) in Hep3B human hepatoma cells. In addition, treatment of
      mice with TNF and IL-1 also decreased RXRalpha, PPARalpha, PPARgamma, LXRalpha,
      and PGC-1alpha messenger RNA (mRNA) levels in the liver. These decreases were
      accompanied by reduced binding of nuclear extracts to RXR, PPAR, and LXR response
      elements and decreased luciferase activity driven by PPAR and LXR response
      elements. In addition, the mRNA levels of proteins regulated by PPARalpha
      (carnitine palmitoyltransferase 1alpha) and LXR (sterol regulatory element
      binding protein) were decreased in Hep3B cells treated with TNF or IL-1. Finally,
      using constructs of the LXRalpha promoter or the PGC-1alpha promoter linked to
      luciferase, we were able to demonstrate that a decrease in transcription
      contributes to the reduction in mRNA levels of nuclear hormone receptors and
      coactivators. Thus, our results suggest that decreased expression of nuclear
      hormone receptors RXRalpha, PPARalpha, PPARgamma, and LXRalpha, as well as
      coactivators PGC-1alpha, PGC-1beta, and SRC-1 may contribute to the cytokine
      induced alterations in hepatic lipid metabolism during the acute phase response.

PMID- 17224346
TI  - Fetal alcohol syndrome: historical perspectives.
AB  - Fetal alcohol syndrome (FAS), the most severe manifestation of the adverse
      effects of alcohol on foetal development, was first described in the French
      medical literature by Lemoine et al. in 1968 [Les Gfants des parents alcholiques:
      anomalies observes a propos de 127 cas (The children of alchoholic parents:
      anomalies observed in 127 cases). Quert in Medicine 8, 476-482]. Five years
      later, Jones et al., 1973. Pattern of malformation in offspring of chronic
      alcholic mothers. Lancet 1, 1129-1267] were the first to delineate systematically
      the association between maternal alcohol abuse and a specific pattern of birth
      defects and to provide diagnostic criteria for this condition. Several diagnostic
      systems have since been developed with a view to capturing the wide spectrum of
      physical and behavioral anomalies resulting from prenatal alcohol exposure. The
      purpose of the current paper is to outline the evolution of FAS as a medical
      diagnosis.

PMID- 17224345
TI  - Short-term energy restriction reduces resting energy expenditure in patients with
      HIV lipodystrophy and hypermetabolism.
AB  - We have previously shown that resting energy expenditure (REE) is increased in
      patients with HIV lipodystrophy. This hypermetabolism could be the result of an
      inadequate storage capacity for lipid fuel secondary to atrophy of the
      subcutaneous adipose tissue depot. Therefore, energy restriction may be able to
      alleviate this hypermetabolism. To test this hypothesis, we measured REE in HIV
      infected patients with lipodystrophy and hypermetabolism and in HIV-infected and
      healthy controls. Measurements were taken during the overnight fasted state after
      3 days on a eu-energetic diet and again after 3 days on a diet of similar
      composition but reduced in energy by 50%. After 3 days of eu-energetic feeding,
      REE was significantly higher in HIV-infected patients with lipodystrophy compared
      with healthy controls (139.5 +/- 1.3 vs 117.2 +/- 1.3 kJ/kg lean body mass, P <
      .001) and tended to be higher compared with HIV-infected subjects without
      lipodystrophy (139.5 +/- 13 vs 127.3 +/- 1.4 kJ/kg lean body mass, P = .06).
      Furthermore, energy restriction caused a significant decline in REE in patients
      with HIV lipodystrophy (P < .001). This dietary manipulation did not lead to a
      significant reduction in REE in either HIV-infected or healthy controls. This
      suggests that energy intake and REE may be uniquely coupled in patients with
      lipodystrophy as a means to dissipate energy that cannot be stored in a normal
      manner. A better understanding of this coupling would have important implications
      for weight regulation in general.

PMID- 17224347
TI  - Chiropractic's current state: impacts for the future.
AB  - The chiropractic profession is currently facing a shift in practice and health
      care environments. This editorial reflects on the current state of the profession
      and suggests that the profession should move from the thinking and practice
      styles of the past that primarily attempted to prove patient care and practice to
      a more productive approach that strives to improve patient care and practice. The
      following primary areas that require attention are discussed: (1) evidence-based
      and best practices-oriented research priorities; (2) constructive engagement of
      the greater health care system; and (3) successful ethical business models.

PMID- 17224349
TI  - Prevalence of modic degenerative marrow changes in the cervical spine.
AB  - OBJECTIVE: The prevalence and distribution of Modic degenerative marrow changes
      as seen on magnetic resonance imaging scans have been reported for the lumbar
      spine, and research suggests that type 1 Modic changes are linked to low back
      pain. The purpose of this study was to report on the prevalence, types, and
      distribution of the changes found for the cervical spine. METHODS: One hundred
      thirty-three cervical spine T1-weighted and T2-weighted sagittal magnetic
      resonance imaging scans were viewed retrospectively by two radiologists. Data
      were recorded for patient age, patient sex, and the presence or absence of Modic
      changes. If Modic changes were present, then the precise vertebral levels of
      these changes and the specific Modic type were recorded. Descriptive statistics
      were calculated for the prevalence of Modic changes overall, the prevalence of
      types 1, 2, and 3 changes, and the prevalence in male vs female patients. The
      frequency of these changes by spinal level was also determined. RESULTS: One
      hundred eighteen patients met the inclusion criteria. Modic changes were seen in
      19 patients (16%), with 4 showing changes in more than one segmental level. The
      most common Modic change observed was type 1. Type 3 marrow changes were the
      second most common category to be noted. Only 3 patients had Modic type 2 marrow
      changes. The most common cervical spinal level to show Modic changes was C5-6.
      CONCLUSIONS: Modic degenerative bone marrow changes are observed in the cervical
      spine, with the C5-6 level being the most commonly involved. Unlike in the lumbar
      spine in which Modic type 2 changes predominate, type 1 marrow changes were far
      more common in the cervical spine. Further studies should focus on the clinical
      relevance of these findings.

PMID- 17224350
TI  - Patient perceptions of chiropractic treatment for primary care disorders.
AB  - OBJECTIVE: Although some surveyed groups of chiropractors consider themselves
      qualified as primary care providers, consumer attitudes of such may affect
      practice success. The purpose of this study is to determine chiropractic
      patients' perception of chiropractors as primary care providers and to determine
      what disorders patients believe chiropractors can treat. METHODS: A 2-page survey
      was developed to collect information from current chiropractic patients at a
      teaching chiropractic clinic in the United States. Questions included (1) brief
      patient demographic information, (2) whether their chiropractor was their primary
      care physician, and (3) patient beliefs about chiropractors assessing and
      treating conditions that are common to a primary care medical practice.
      Conditions listed in the survey were based on a previous study on primary care
      medical physicians' practices. The sample of chiropractic patients was divided
      into suburban, urban, and chiropractic university-affiliated patients. RESULTS:
      There were 163 subjects who responded to this survey for a 58% response rate.
      Only 19% (30/157) saw their chiropractor as their primary care physician.
      However, for each 'primary care condition' listed, the percent of patients who
      affirmed that chiropractors could treat the condition varied greatly with many
      conditions showing an affirmative response of higher than 50% especially in the
      urban and university-affiliated patient groups. All patients overwhelmingly
      believed that chiropractors could treat musculoskeletal conditions. CONCLUSIONS:
      Patients have varied views of what chiropractors can and cannot treat. Further
      studies are needed to determine the effectiveness of chiropractic treatment for
      specific primary care disorders. The results of such studies may be the
      determining influence for public and physician opinion on the appropriateness of
      chiropractic care for these conditions.

PMID- 17224351
TI  - Manual forces applied during cervical mobilization.
AB  - OBJECTIVE: Manual therapists routinely use passive accessory mobilization
      techniques to treat patients with mechanical neck disorders, but little is known
      about the manual forces applied. The aim of this study was to quantify the manual
      forces applied to the cervical spine during joint mobilization. METHODS: Ten
      physiotherapists performed posterior-to-anterior mobilizations to C2 and C7 (both
      centrally and unilaterally, 1 right and 1 left, grades I-IV) on a single
      asymptomatic male subject. Manual forces were measured in 3 planes using an
      instrumented treatment table. RESULTS: The instrumented table showed excellent
      reliability (intraclass correlation coefficient [2,1], 0.99; 95% confidence
      interval, 0.97-1.00) and accuracy (mean absolute error; vertical force, 1.1 N;
      SD, 1.5). There were considerable differences between therapists for mean peak
      force, force amplitude, and oscillation frequency for each technique and grade.
      Mean peak forces (grade I, 21.8 N; SD, 15.0; grade II, 34.9 N; SD, 20.9; grade
      III, 58.2 N; SD, 27.5; grade IV, 61.0 N; SD, 29.9) were considerably lower than
      previously reported lumbar mobilization forces. Intratherapist repeatability for
      all mobilization parameters was high. Force amplitude and oscillation frequency
      measures indicated that therapists generally adhered to the published definitions
      of the grades of mobilization when applying force, but when asked, provided quite
      different definitions of the grades. CONCLUSIONS: This study provides preliminary
      evidence that cervical mobilization forces vary considerably between therapists,
      but intratherapist repeatability is high.

PMID- 17224352
TI  - Reproduction of the lumbar lordosis: a comparison of standing radiographs versus
      supine magnetic resonance imaging obtained with straightened lower extremities.
AB  - OBJECTIVE: This study investigates whether it is possible to reproduce the lumbar
      lordosis in the upright position during magnetic resonance imaging (MRI) by
      positioning the patient supine with straightened lower extremities and
      investigates intra- and interexaminer reliability of measurements of the lumbar
      lordosis on radiographs and MRI. METHODS: This was an observational study, which
      included an intra- and interexaminer reliability study. The lumbar lordosis was
      measured digitally on radiographs taken from 22 patients in an upright standing
      position, and 22 MRI scans of the same patients lying supine with straightened
      lower extremities. These measurements were compared statistically. Intra- and
      interexaminer reliability was calculated applying the Bland and Altman method.
      RESULTS: The lumbar lordosis in the standing position was reproduced in the
      straightened supine position with a median deviation of 3 degrees . Intra- and
      interexaminer reliability was better for MRI than for radiographs. The mean
      differences were close to 0, especially for interexaminer reliability during MRI.
      On radiographs, there was a higher agreement on interexaminer than on intra
      examiner reliability. CONCLUSION: The findings of this study show that lumbar
      lordosis in the upright position can be reproduced by positioning the patient
      supine with straightened lower extremities.

PMID- 17224353
TI  - Dynamic surface electromyographic responses in chronic low back pain treated by
      traditional bone setting and conventional physical therapy.
AB  - OBJECTIVE: This study compared the dynamic surface electromyographic (EMG)
      activities of back muscles and pain before and after traditional bone setting and
      physical therapy. METHODS: This study was a prospective clinical trial that
      compared surface EMG dynamic activities after traditional bone setting and
      physical therapy. Sixty-one patients (mean age, 41 years) with nonspecific low
      back pain were randomized into two subgroups by treatment. The patients underwent
      a dynamic EMG evaluation for which they were asked to stand and then bend forward
      as far as possible, stay fully flexed, and return to standing. A flexion
      relaxation ratio was calculated by comparing maximal EMG activity while flexing
      with the average EMG activity in full flexion. Concentric (maximal EMG activity
      during extension) and eccentric (maximal EMG activity during flexion) ratios were
      also used in the analyses. RESULTS: Disability, depression, and visual analog
      scale scores decreased significantly after both treatments. The concentric ratio
      increased statistically in both groups after the treatments. The study failed to
      show a significant association between experienced back pain and EMG parameters.
      CONCLUSIONS: Both treatments seem to have a positive influence on back muscle
      function by improving muscle symmetry; however, the treatments had no effect on
      the flexion-relaxation phenomenon after 1 month. Active back exercise at home
      together with rehabilitation treatments might be effective and improve function
      for patients with chronic low back pain.

PMID- 17224354
TI  - Development of a computerized intervertebral motion analysis of the cervical
      spine for clinical application.
AB  - OBJECTIVE: The objective of this study was to develop a measurement method that
      could be implemented in chiropractic for the evaluation of angular and
      translational intervertebral motion of the cervical spine. METHODS: Flexion
      extension radiographs were digitized with a scanner at a ratio of 1:1 and
      imported into a software, allowing segmental motion measurements. The
      measurements were obtained by selecting the most anteroinferior point and the
      most posteroinferior point of a vertebral body (anterior and posterior arch,
      respectively, for C1), with the origin of the reference frame set at the most
      posteroinferior point of the vertebral body below. The same procedure was
      performed for both the flexion and extension radiographs, and the coordinates of
      the 2 points were used to calculate the angular movement and the translation
      between the 2 vertebrae. RESULTS: This method provides a measure of
      intervertebral angular and translational movement. It uses a different reference
      frame for each joint instead of the same reference frame for all joints and thus
      provides a measure of motion in the plane of each articulation. The calculated
      values obtained are comparable to other studies on intervertebral motion and
      support further development to validate the method. CONCLUSION: The present study
      proposes a computerized procedure to evaluate intervertebral motion of the
      cervical spine. This procedure needs to be validated with a reliability study but
      could provide a valuable tool for doctors of chiropractic and further spinal
      research.

PMID- 17224355
TI  - An examination of musculoskeletal cognitive competency in chiropractic interns.
AB  - OBJECTIVE: This study investigates the cognitive competency of final-year
      chiropractic students in musculoskeletal medicine. METHODS: The face, content,
      and criterion validity of the Basic Clinical Examination (BCE) for
      musculoskeletal medicine were tested for use in chiropractic education. After
      validity testing, the BCE was administered in a cross-sectional design to all
      fourth year students (154) attending the Canadian Memorial Chiropractic College.
      RESULTS: Twenty percent (5 questions) of the BCE was deemed not relevant or
      outside of the scope of practice by criterion experts. One hundred twenty-three
      (80%) fourth year chiropractic interns participated in the cross-sectional study.
      Interns achieved a 51.2% passing rate (mean score, 73.2%; 95% confidence
      interval, 82%-71.8%) for the 25-item BCE, whereas the criterion experts achieved
      a 100% passing rate. For the modified 20-item BCE, the interns' mean score was
      80.8%, whereas the criterion experts' mean score rose to 92.8%. CONCLUSIONS: Most
      final-year chiropractic interns at this college were [corrected] found to be
      competent in musculoskeletal medicine as assessed by the Basic Competency
      Examination. This is in contradiction to previous work with medical students,
      recent medical graduates, nonorthopedic staff physicians, osteopathic students,
      and physical therapy students. Chiropractic clinicians with postgraduate training
      showed considerably better results than chiropractic interns. Problems pertaining
      to the content validity (relevance and scope of practice for chiropractors) of
      the BCE need to be addressed.

PMID- 17224356
TI  - A pilot study comparing two manual therapy interventions for carpal tunnel
      syndrome.
AB  - OBJECTIVE: The purpose of this study was to determine the clinical efficacy of
      manual therapy interventions for relieving the signs and symptoms of carpal
      tunnel syndrome (CTS) by comparing 2 forms of manual therapy techniques: Graston
      Instrument-assisted soft tissue mobilization (GISTM) and STM administered with
      the clinician hands. METHODS: The study was a prospective comparative research
      design in the setting of a research laboratory. Volunteers were recruited with
      symptoms suggestive of CTS based upon a phone interview and confirmed by
      electrodiagnostic study findings, symptom characteristics, and physical
      examination findings during an initial screening visit. Eligible patients with
      CTS were randomly allocated to receive either GISTM or STM. Interventions were,
      on average, twice a week for 4 weeks and once a week for 2 additional weeks.
      Outcome measures included (1) sensory and motor nerve conduction evaluations of
      the median nerve; (2) subjective pain evaluations of the hand using visual analog
      scales and Katz hand diagrams; (3) self-reported ratings of symptom severity and
      functional status; and (4) clinical assessments of sensory and motor functions of
      the hand via physical examination procedures. Parametric and nonparametric
      statistics compared treated CTS hand and control hand and between the treatment
      interventions, across time (baseline, immediate post, and at 3 months' follow
      up). RESULTS: After both manual therapy interventions, there were improvements to
      nerve conduction latencies, wrist strength, and wrist motion. The improvements
      detected by our subjective evaluations of the signs and symptoms of CTS and
      patient satisfaction with the treatment outcomes provided additional evidence for
      the clinical efficacy of these 2 manual therapies for CTS. The improvements were
      maintained at 3 months for both treatment interventions. Data from the control
      hand did not change across measurement time points. CONCLUSIONS: Although the
      clinical improvements were not different between the 2 manual therapy techniques,
      which were compared prospectively, the data substantiated the clinical efficacy
      of conservative treatment options for mild to moderate CTS.

PMID- 17224357
TI  - A congenital anomaly of the atlas as a diagnostic dilemma: a case report.
AB  - OBJECTIVE: The purpose of this case report is to draw attention to the
      differences between a Jefferson fracture and a congenital anomaly of the anterior
      and/or the posterior arch of the atlas. CLINICAL FEATURES: A 42-year-old woman
      visited the chiropractic practice complaining of headache, neck pain, dizziness,
      and numbness in both of her arms after she fell vertically and directly on her
      head twice on a playground. Before this fall, she had no such complaints. After
      taking x-rays of the cervical spine, a Jefferson fracture was suspected.
      INTERVENTION AND OUTCOME: After computed tomography and magnetic resonance
      imaging scanning, the patient was diagnosed with a congenital anomaly that looked
      very similar to a Jefferson fracture. After instability of the cervical spine was
      excluded by the neurosurgeon, chiropractic treatment was delivered. After 6
      treatments, the complaints were significantly reduced. CONCLUSION: It is
      important to be familiar with the differences between a congenital anomaly of the
      atlas and a Jefferson fracture and to exclude instability of the upper cervical
      spine before treatment is started.

PMID- 17224358
TI  - Resolution of symptoms of chronic constipation in an 8-year-old male after
      chiropractic treatment.
AB  - OBJECTIVE: This case report describes the history, treatment, and proposed
      explanation of a positive outcome in a patient with chronic constipation.
      CLINICAL FEATURES: An 8-year-old boy presented with chronic constipation. His
      mother reported that this had been a problem since the child's birth. Allopathic
      treatment consisting of laxatives, high fluid intake, and high fiber intake had
      not been effective to date. INTERVENTION AND OUTCOME: The patient was examined
      and it was determined that he had a sacral chiropractic subluxation complex.
      Manipulation of the sacral area using diversified adjusting procedures was
      performed. External massage of the abdomen starting in the right lower quadrant
      and following the course of the large intestine in a clockwise direction was also
      applied. The patient reported an immediate dramatic improvement in bowel function
      after the first treatment. Treatment was continued for a 4-week period (2 visits
      per week) and then discontinued when the patient (confirmed by his mother)
      reported consistent normal bowel function. A follow-up call made 13 years after
      treatment revealed continuing normal bowel function. CONCLUSION: This case
      suggests that chiropractic care may be helpful in some cases of chronic
      constipation.

PMID- 17224359
TI  - Clinical assessment of scapular positioning in patients with shoulder pain: state
      of the art.

PMID- 17224360
TI  - Spinal manipulation reduces pain and hyperalgesia after lumbar intervertebral
      foramen inflammation in the rat.

PMID- 17224362
TI  - Relative responsiveness of 3 different types of clinical outcome measures on
      chiropractic patients with low back pain.

PMID- 17224364
TI  - Influence of axial rotation on chiropractic pelvic analysis.

PMID- 17224365
TI  - Toxic epidermal necrolysis.
AB  - Toxic epidermal necrolysis (TEN) is an unpredictable, life-threatening drug
      reaction associated with a 30% mortality. Massive keratinocyte apoptosis is the
      hallmark of TEN. Cytotoxic T lymphocytes appear to be the main effector cells and
      there is experimental evidence for involvement of both the Fas-Fas ligand and
      perforin/granzyme pathways. Optimal treatment for these patients remains to be
      clarified. Discontinuation of the offending drug and prompt referral to a burn
      unit are generally agreed upon steps. Beyond that, however, considerable
      controversy exists. Evidence both pro and con exists for the use of IVIG,
      systemic corticosteroid, and other measures. There is also evidence suggesting
      that combination therapies may be of value. All the clinical data, however, is
      anecdotal or based on observational or retrospective studies. Definitive answers
      are not yet available. Given the rarity of TEN and the large number of patients
      required for a study to be statistically meaningful, placebo controlled trials
      are logistically difficult to accomplish. The absence of an animal model further
      hampers research into this condition. This article reviews recent data concerning
      clinical presentation, pathogenesis and treatment of TEN. LEARNING OBJECTIVES: At
      the conclusion of this learning activity, participants should have acquired a
      more comprehensive knowledge of our current understanding of the classification,
      clinical presentation, etiology, pathophysiology, prognosis, and treatment of
      TEN.

PMID- 17224366
TI  - Stealth monitoring of adherence to topical medication: adherence is very poor in
      children with atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis is a common problem for which topical agents are
      the primary treatment. When topical medications fail, further therapy may include
      systemic agents with the potential for greater toxicity. Adherence to topical
      treatment of atopic dermatitis has not been well characterized. Poor adherence to
      topical medication could account for failure of topical therapy. PURPOSE: To
      determine adherence to topical treatment in patients with atopic dermatitis.
      METHODS: Thirty-seven children were given 0.1% triamcinolone ointment and were
      counseled to use it twice daily. They were told to return in 4 weeks, at which
      time they were told to continue treatment for another 4 weeks. Electronic
      monitors were used to measure adherence over the entire 8 week study. Patients
      were not informed of the compliance monitoring until the end of the study.
      RESULTS: Twenty-six patients completed 8 weeks of treatment. Mean adherence from
      the baseline to the end of the study was 32%. Adherence was higher on or near
      office visit days and subsequently decreased rapidly. LIMITATIONS: This study was
      limited by the large number of subjects who failed to return for follow-up
      appointments or withdrew from the study. CONCLUSIONS: Adherence to topical
      medications is very poor in a clinic population of children with atopic
      dermatitis. Office visits are one means to increase adherence. If adherence to
      topical treatment can be improved, exposure to more costly and potentially toxic
      systemic agents may be avoidable.

PMID- 17224367
TI  - High-potency steroid use in children with vitiligo: a retrospective study.
AB  - BACKGROUND: Data on efficacy and safety of treatments in children with vitiligo
      are limited. OBJECTIVE: We sought to describe the clinical outcomes and safety of
      children with vitiligo treated with high-potency topical corticosteroids.
      METHODS: Clinical improvement and laboratory data were retrospectively analyzed
      in 101 children (0-18 years) with vitiligo treated with moderate- to high-potency
      topical corticosteroids. RESULTS: Of patients, 64% (45 of 70) had repigmentation
      of the lesions, 24% (17 of 70) showed no change, and 11% (8 of 70) were worse
      than at the initial presentation. Local steroid side effects were noted in 26% of
      patients at 81.7 +/- 44 days of follow-up. Cortisol levels were abnormal in 29%
      of patients (21 of 73). Two children with low cortisol levels were given the
      diagnosis of steroid-induced adrenal suppression. Children with normal and
      abnormal cortisol levels were not significantly different by sex, age of onset,
      potency of the corticosteroid use, or family history. However, children with head
      and/or neck affected areas were 8.36 times more likely to have an abnormal
      cortisol level compared with children affected in other body areas (RR 95%
      confidence interval: 1.19, 58.60, P = .003, n = 72). Of patients, 8% (6 of 74)
      had an abnormal thyrotropin test result. LIMITATIONS: The retrospective design of
      this study presents inherent limitations. CONCLUSION: Moderate- to high-potency
      topical corticosteroids are efficacious in children with vitiligo, but may be
      associated with systemic absorption.

PMID- 17224368
TI  - Clinical diagnosis of incontinentia pigmenti in a cohort of male patients.
AB  - Eighteen male patients with incontinentia pigmenti (IP) showed the characteristic
      clinical features and, when examined, histologic skin defects observed in female
      patients with IP. Six of the patients had neurologic, ophthalmologic, or dental
      manifestations as well. Three patients showed evidence by polymerase chain
      reaction analysis of both the normal NEMO gene and the exon 4-10 deletion in NEMO
      that occurs in the majority of affected girls with IP, confirming postzygotic
      mosaicism for the NEMO gene.

PMID- 17224369
TI  - Efficacy, predictors of response, and long-term follow-up in patients with
      vitiligo treated with narrowband UVB phototherapy.
AB  - BACKGROUND: Narrowband UVB (NB-UVB) phototherapy is considered an accepted
      therapy for vitiligo. OBJECTIVE: We sought to estimate the effectiveness of NB
      UVB in patients with vitiligo, identify predictive factors of response, and
      assess the stability of NB-UVB-induced repigmentation. METHODS: In all, 70
      patients with vitiligo were treated twice weekly with NB-UVB. RESULTS:
      Cosmetically acceptable (>75%) repigmentation was achieved in 34.4% of patients
      with lesions on the face and in 7.4% of patients with lesions on the body.
      Patients with phototypes III to V had a greater chance to achieve greater than
      75% repigmentation on the face. Patients who responded in the first month of
      treatment were more likely to achieve better repigmentation rates. Repigmentation
      was stable in 14.3% of patients 4 years after cessation of treatment.
      LIMITATIONS: The study was uncontrolled. Treatment frequency was twice weekly.
      These results may not be representative of different treatment regimens.
      CONCLUSION: Patients with vitiligo who have lesions on the face, darker
      phototypes, and early response to treatment have a greater chance to achieve
      satisfactory repigmentation after NB-UVB phototherapy.

PMID- 17224370
TI  - Reporting of ethical review of clinical research submitted to the Journal of the
      American Academy of Dermatology.
AB  - BACKGROUND: In recent years there has been an increasing focus on human subject
      protection and on documentation of ethical review in published clinical research.
      The JAAD clearly states in its instructions to authors, which adhere to the
      guidelines set forth by the International Committee of Medical Journal Editors,
      "studies involving live human subjects must have been approved by the author's
      Institutional Review Board or its equivalent." OBJECTIVE: To determine what
      proportion of prospective studies on human subjects submitted to the clinical
      trials and therapeutics section lacked mention of review by an ethics board and
      to determine the outcome of these manuscripts. METHODS: We reviewed 150
      prospective studies submitted from July 1, 2004 to January 16, 2006 to a single
      associate editor, who receives the majority of reports requiring ethics board
      review. RESULTS: Of 150 prospective studies, 36% (n = 54) had no mention of
      ethics review or consent, whereas 15% (n = 22) mentioned consent but not ethics
      review. Forty-two papers were returned asking for ethics information, and of
      these, 48% were resubmitted with confirmation of ethics review, 22% were
      withdrawn, 12% were never resubmitted, 12% responded that ethical review was not
      obtained, and 7% were clarified as exempt from review. Of the 150 papers, 45%
      were from US authors and 55% were from international authors. Sixty-seven percent
      of US papers and 35% of international papers included ethics board information (P
      <or= .001). Of the remaining authors who did not initially provide information on
      ethics review, 25% of US and 53% of international authors were able to provide
      documentation of ethics board review when asked. Of international authors asked
      for ethics information, 67% of European authors provided confirmation of ethical
      review, as compared with 48% of non-European authors. LIMITATIONS: It is not
      possible to know with certainty whether each study not citing ethics review
      actually did not undergo review by an ethics board. Additionally, other editors
      may have handled some studies requiring ethics review. CONCLUSIONS: One half of
      authors submitting papers on prospective clinical studies to the JAAD did not
      provide evidence of ethical review on initial submission. The reason for omission
      was likely oversight in half of the cases, but in others ethics review and
      approval were likely not obtained. International authors were more likely to omit
      mention of ethics review, but, although sample size was too small for statistical
      analysis, international authors were more often able to provide it when asked,
      suggesting oversight or misunderstanding as a reason for omission. Furthermore,
      ethics review may be more standard in the European Union, as European authors
      were more likely to be able to provide the information when asked, although small
      sample size precluded statistical analysis.

PMID- 17224371
TI  - Technique for calcium hydroxylapatite injection for correction of nasolabial fold
      depressions.
AB  - BACKGROUND: Injectable calcium hydroxylapatite is a soft-tissue augmentation
      material that is used off-label for facial augmentation, including repletion of
      depressed nasolabial folds. OBJECTIVE: We sought to assess the safety of calcium
      hydroxylapatite injection for correction of nasolabial fold depressions.
      Specifically, we sought to obtain a quantitative assessment of injection-related
      adverse events using a reproducible placement technique with long-term follow-up.
      METHODS: We conducted an open-label, single-center prospective study using
      reproducible technique with 1- to 1.5-year follow-up. All patients were treated
      with infraorbital nerve blocks. Then, parallel linear threading technique using
      27-gauge/1.25-in needles was used to place 1 to 2 mL of injectant at the dermal
      subcutaneous junction into each pair of depressed folds. A triangular array of
      injectant was deposited under the melonasal junction. At follow-up at 2 to 3
      weeks and at 1 to 1.5 years, respectively, patients were asked to report and
      characterize injection-related redness, swelling, bruising, nodule or granuloma
      formation, asymmetric correction, textural change, hypersensitivity reactions,
      degree of correction remaining, and overall satisfaction. In addition, patients
      who had received other injectable soft-tissue materials were asked to compare
      these with calcium hydroxylapatite in terms of risk profile and longevity of
      effect. RESULTS: In all, 22 patients were treated and complete follow-up data
      were obtained from 18. Of the 18 patients, all reported at least mild
      postinjection redness and swelling, which abated within 1 to 5 days. Bruising was
      reported by fewer than half, and resolved within 4 to 10 days. Palpable but not
      visible nodules were reported by 2 of 18 patients; these resolved within 3 months
      of injection. Asymmetric correction, textural change, granulomas, and
      hypersensitivity reactions were not reported. In all, 14 of 18 patients reported
      that cosmetically significant correction lasted longer than 1 year. Two thirds of
      injected patients who had received other fillers for nasolabial fold correction
      preferred calcium hydroxylapatite, with the primary reason being increased
      longevity of effect. LIMITATIONS: There was a lack of objective outcomes
      measures. CONCLUSIONS: When a consistent, defined injection technique is used,
      injectable calcium hydroxylapatite appears to be a well-tolerated soft-tissue
      augmentation material for correction of nasolabial fold depressions. A long
      duration of effect may make this material particularly desirable for some
      patients.

PMID- 17224373
TI  - Topical therapy of atopic dermatitis: controversies from Hippocrates to topical
      immunomodulators.
AB  - Although atopic dermatitis can be treated efficiently, there is still much
      controversy about the risk/benefit ratio of both topical corticosteroids and
      topical immunomodulators. Conflicting data may be found about the usefulness of
      bathing, diet regulation, and other therapeutic interventions. These
      controversies result in part from the persistence of Hippocratic doctrines in
      modern medical thinking. Humoralist and diathetic doctrines, as they pertain to
      eczema, are reviewed. The paradoxical worsening of oozing and the deadly hazards
      of hospitalization before the era of antibiotics are brought to mind. We hope
      that this historical review will improve the understanding of current
      controversies and help dermatologists to manage patients with atopic dermatitis
      and other chronic skin diseases.

PMID- 17224372
TI  - Congenital self-healing reticulohistiocytosis (Hashimoto-Pritzker disease): ten
      year experience at Dallas Children's Medical Center.
AB  - The real incidence of congenital self-healing reticulohistiocytosis (CSHR) may be
      underreported because of its high rate of spontaneous resolution and lack of
      clinical recognition. Currently, there are no criteria other than clinical that
      can reliably distinguish CSHR from cutaneous involvement by disseminated
      Langerhans cell histiocytosis (LCH). In this study we investigate the role of E
      cadherin, Ki-67, and phosphorylated histone H3 (PHH3) immunohistochemical stains
      in distinguishing CSHR from disseminated LCH. We found that no significant
      difference was seen in the histologic features and the expression of E-cadherin,
      Ki-67, and PHH3 between the two groups; thus supporting the theory that CSHR and
      LCH represent different ends of a spectrum of the same condition.

PMID- 17224374
TI  - Tumor necrosis factor inhibitor-induced pustular psoriasis?
AB  - Dialogues in Dermatology, a monthly audio program from the American Academy of
      Dermatology, contains discussions between dermatologists on timely topics.
      Commentaries from Dialogues Editor-in-Chief Warren R. Heymann, MD, are provided
      after each discussion as a topic summary and are provided here as a special
      service to readers of the Journal of the American Academy of Dermatology.

PMID- 17224375
TI  - Innovative care, medical research, and the ethics of informed consent.

PMID- 17224376
TI  - Drug companies, dermatologists, and the patient.

PMID- 17224377
TI  - Institutional review board use among dermatology researchers.

PMID- 17224378
TI  - Sentinel lymph node biopsy for melanoma is still controversial.

PMID- 17224379
TI  - Extracorporeal photopheresis in systemic sclerosis: effects on organ involvement?

PMID- 17224380
TI  - Acral acanthosis nigricans (acral acanthotic anomaly).

PMID- 17224381
TI  - Reply: Tattoos and body piercing.

PMID- 17224383
TI  - Acquired hypertrichosis lanuginosa as a presenting sign of metastatic prostate
      cancer with rapid resolution after treatment.
AB  - BACKGROUND: Acquired hypertrichosis lanuginosa (AHL) is a rare cutaneous disorder
      that involves spontaneous growth of lanugo-type hair in association with overt or
      occult malignant neoplasms. Bronchopulmonary and gastrointestinal malignancies
      are most commonly associated. CASE PRESENTATION: We report the occurrence of AHL
      associated with metastatic prostate cancer and its abrupt resolution after
      bilateral orchiectomy. To our knowledge, this is the first reported case of an
      association with prostate cancer. LIMITATIONS: The case presented represents a
      single patient; therefore, the findings and results reported may not be
      applicable to all patient populations. CONCLUSION: A variety of cutaneous
      findings are considered warning indicators of underlying neoplastic disease.
      Physician awareness of such signs can prompt timely and potentially life-saving
      investigations and interventions. AHL is regarded as such a sign. Physician
      awareness of the addition of prostate cancer to the growing list of AHL
      associated malignancies provides rationale for appropriate testing and referral.

PMID- 17224382
TI  - Keratosis lichenoides chronica in pediatric patients: a different disease?
AB  - Keratosis lichenoides chronica (KLC) is a rare acquired disease of adulthood, of
      unknown etiology, characterized by keratotic parallel linear lesions, retiform
      plaques, and keratotic, often follicular papules, chronicity and lichenoid
      histopathologic features. KLC of pediatric onset is considered extremely rare.
      Its features and relationship to adult onset KLC are unknown. We studied 8 cases
      of pediatric-onset KLC in the literature and 6 personal cases and compared them
      with 40 reported adult-onset KLC patients. The following features characterize
      pediatric-onset KLC: familial occurrence; probable autosomal recessive
      inheritance; early or congenital onset with facial erythemato-purpuric macules;
      forehead, eyebrow, and eyelash alopecia; pruritus; and a low frequency of other
      cutaneous and systemic abnormalities. Pediatric-onset KLC may represent a
      different disease or a subset of adult-onset KLC, with special genetic and
      clinical characteristics. Determining its precise nosology will have prognostic
      and therapeutic implications.

PMID- 17224385
TI  - Infantile pyramidal protrusion localized at the vulva as a manifestation of
      lichen sclerosus et atrophicus.

PMID- 17224386
TI  - Wells' syndrome after primoinfection by parvovirus B19 in a child.

PMID- 17224384
TI  - Norwegian scabies mimicking onychomycosis and scalp dermatitis in a child with
      IPEX syndrome.

PMID- 17224387
TI  - Bilateral symmetric facial epidermal nevus.

PMID- 17224388
TI  - Ehlers-Danlos syndrome type IV: keloidal plaques of the lower extremities,
      amniotic band limb deformity, and a new mutation.

PMID- 17224389
TI  - An infant with extensive cutaneous nodular juvenile xanthogranuloma and
      hyperlipidemia.

PMID- 17224390
TI  - Nevus lipomatosus cutaneous superficialis with folliculosebaceous cystic
      hamartoma.

PMID- 17224392
TI  - Cholangiocarcinoma with skin metastases.

PMID- 17224393
TI  - Eosinophilic, polymorphic, and pruritic eruption associated with radiotherapy in
      a patient with breast cancer.

PMID- 17224391
TI  - Keratoacanthoma developing on nevus sebaceous in a child.

PMID- 17224394
TI  - Sweet's panniculitis associated with metastatic breast cancer.

PMID- 17224395
TI  - Third-trimester impetigo herpetiformis treated with cyclosporine.

PMID- 17224397
TI  - Semaphorin directs axon traffic in the fly olfactory system.
AB  - The convergence of olfactory sensory axons that express the same receptor onto
      specific glomeruli is a common organizing principle in animal olfactory systems.
      In this issue of Neuron, two beautiful studies in Drosophila by Lattemann et al.
      and Sweeney et al. show that Semaphorin repulsion regulates interactions between
      olfactory receptor neurons to help axons find their correct targets.

PMID- 17224398
TI  - A neural protection racket: AMPK and the GABA(B) receptor.
AB  - The cellular energy-sensing kinase AMPK is known to be activated in neurons in
      response to metabolic insults, but the downstream consequences have been unclear.
      A study by Kuramoto and colleagues in this issue of Neuron favors the idea that
      AMPK activation is neuroprotective, and suggests a potential mechanism for this
      effect involving phosphorylation of the GABA(B) receptor.

PMID- 17224399
TI  - Paving the way forward: integrating the senses through phase-resetting of
      cortical oscillations.
AB  - Most, if not all, of the neocortex is multisensory, but the mechanisms by which
      different cortical areas - association versus sensory, for instance - integrate
      multisensory inputs are not known. The study by Lakatos et al. reveals that, in
      the primary auditory cortex, the phase of neural oscillations is reset by
      somatosensory inputs, and subsequent auditory inputs are enhanced or suppressed,
      depending on their timing relative to the oscillatory cycle.

PMID- 17224400
TI  - Does the parietal cortex distinguish between "10," "ten," and ten dots?
AB  - It is well established that the intraparietal sulcus (IPS) plays an important
      role in the processing and representation of numerical magnitude. Two recent
      studies by Piazza et al. and Cohen Kadosh et al. published in this issue of
      Neuron used fMRI adaptation to explore the extent to which parietal number
      processing is dependent upon or independent of a numbers' surface format. Their
      results, while slightly different, converge to suggest that the answer may be
      neither, but rather that it depends on the hemisphere.

PMID- 17224401
TI  - Semaphorin-1a controls receptor neuron-specific axonal convergence in the primary
      olfactory center of Drosophila.
AB  - In the olfactory system of Drosophila, 50 functional classes of sensory receptor
      neurons (ORNs) project in a highly organized fashion into the CNS, where they
      sort out from one another and converge into distinct synaptic glomeruli. We
      identified the transmembrane molecule Semaphorin-1a (Sema-1a) as an essential
      component to ensure glomerulus-specific axon segregation. Removal of sema-1a in
      ORNs does not affect the pathfinding toward their target area but disrupts local
      axonal convergence into a single glomerulus, resulting in two distinct targeting
      phenotypes: axons either intermingle with adjacent ORN classes or segregate
      according to their odorant receptor identity into ectopic sites. Differential
      Sema-1a expression can be detected among neighboring glomeruli, and mosaic
      analyses show that sema-1a functions nonautonomously in ORN axon sorting. These
      findings provide insights into the mechanism by which afferent interactions lead
      to synaptic specificity in the olfactory system.

PMID- 17224402
TI  - Temporal target restriction of olfactory receptor neurons by Semaphorin
      1a/PlexinA-mediated axon-axon interactions.
AB  - Axon-axon interactions have been implicated in neural circuit assembly, but the
      underlying mechanisms are poorly understood. Here, we show that in the Drosophila
      antennal lobe, early-arriving axons of olfactory receptor neurons (ORNs) from the
      antenna are required for the proper targeting of late-arriving ORN axons from the
      maxillary palp (MP). Semaphorin-1a is required for targeting of all MP but only
      half of the antennal ORN classes examined. Sema-1a acts nonautonomously to
      control ORN axon-axon interactions, in contrast to its cell-autonomous function
      in olfactory projection neurons. Phenotypic and genetic interaction analyses
      implicate PlexinA as the Sema-1a receptor in ORN targeting. Sema-1a on antennal
      ORN axons is required for correct targeting of MP axons within the antennal lobe,
      while interactions amongst MP axons facilitate their entry into the antennal
      lobe. We propose that Sema-1a/PlexinA-mediated repulsion provides a mechanism by
      which early-arriving ORN axons constrain the target choices of late-arriving
      axons.

PMID- 17224403
TI  - PAR-1 kinase phosphorylates Dlg and regulates its postsynaptic targeting at the
      Drosophila neuromuscular junction.
AB  - Targeting of synaptic molecules to their proper location is essential for
      synaptic differentiation and plasticity. PSD-95/Dlg proteins have been
      established as key components of the postsynapse. However, the molecular
      mechanisms regulating the synaptic targeting, assembly, and disassembly of PSD
      95/Dlg are not well understood. Here we show that PAR-1 kinase, a conserved cell
      polarity regulator, is critically involved in controlling the postsynaptic
      localization of Dlg. PAR-1 is prominently localized at the Drosophila
      neuromuscular junction (NMJ). Loss of PAR-1 function leads to increased synapse
      formation and synaptic transmission, whereas overexpression of PAR-1 has the
      opposite effects. PAR-1 directly phosphorylates Dlg at a conserved site and
      negatively regulates its mobility and targeting to the postsynapse. The ability
      of a nonphosphorylatable Dlg to largely rescue PAR-1-induced synaptic defects
      supports the idea that Dlg is a major synaptic substrate of PAR-1. Control of Dlg
      synaptic targeting by PAR-1-mediated phosphorylation thus constitutes a critical
      event in synaptogenesis.

PMID- 17224404
TI  - An RNAi-based approach identifies molecules required for glutamatergic and
      GABAergic synapse development.
AB  - We report the results of a genetic screen to identify molecules important for
      synapse formation and/or maintenance. siRNAs were used to decrease the expression
      of candidate genes in neurons, and synapse development was assessed. We surveyed
      22 cadherin family members and demonstrated distinct roles for cadherin-11 and
      cadherin-13 in synapse development. Our screen also revealed roles for the class
      4 Semaphorins Sema4B and Sema4D in the development of glutamatergic and/or
      GABAergic synapses. We found that Sema4D affects the formation of GABAergic, but
      not glutamatergic, synapses. Our screen also identified the activity-regulated
      small GTPase Rem2 as a regulator of synapse development. A known calcium channel
      modulator, Rem2 may function as part of a homeostatic mechanism that controls
      synapse number. These experiments establish the feasibility of RNAi screens to
      characterize the mechanisms that control mammalian neuronal development and to
      identify components of the genetic program that regulate synapse formation and/or
      maintenance.

PMID- 17224405
TI  - Phospho-dependent functional modulation of GABA(B) receptors by the metabolic
      sensor AMP-dependent protein kinase.
AB  - GABA(B) receptors are heterodimeric G protein-coupled receptors composed of R1
      and R2 subunits that mediate slow synaptic inhibition in the brain by activating
      inwardly rectifying K(+) channels (GIRKs) and inhibiting Ca(2+) channels. We
      demonstrate here that GABA(B) receptors are intimately associated with 5'AMP
      dependent protein kinase (AMPK). AMPK acts as a metabolic sensor that is potently
      activated by increases in 5'AMP concentration that are caused by enhanced
      metabolic activity, anoxia, or ischemia. AMPK binds the R1 subunit and directly
      phosphorylates S783 in the R2 subunit to enhance GABA(B) receptor activation of
      GIRKs. Phosphorylation of S783 is evident in many brain regions, and is increased
      dramatically after ischemic injury. Finally, we also reveal that S783 plays a
      critical role in enhancing neuronal survival after ischemia. Together our results
      provide evidence of a neuroprotective mechanism, which, under conditions of
      metabolic stress or after ischemia, increases GABA(B) receptor function to reduce
      excitotoxicity and thereby promotes neuronal survival.

PMID- 17224406
TI  - Nonlinear regulation of unitary synaptic signals by CaV(2.3) voltage-sensitive
      calcium channels located in dendritic spines.
AB  - The roles of voltage-sensitive sodium (Na) and calcium (Ca) channels located on
      dendrites and spines in regulating synaptic signals are largely unknown. Here we
      use 2-photon glutamate uncaging to stimulate individual spines while monitoring
      uncaging-evoked excitatory postsynaptic potentials (uEPSPs) and Ca transients. We
      find that, in CA1 pyramidal neurons in acute mouse hippocampal slices, CaV(2.3)
      voltage-sensitive Ca channels (VSCCs) are found selectively on spines and act
      locally to dampen uncaging-evoked Ca transients and somatic potentials. These
      effects are mediated by a regulatory loop that requires opening of CaV(2.3)
      channels, voltage-gated Na channels, small conductance Ca-activated potassium
      (SK) channels, and NMDA receptors. Ca influx through CaV(2.3) VSCCs selectively
      activates SK channels, revealing the presence of functional Ca microdomains
      within the spine. Our results suggest that synaptic strength can be modulated by
      mechanisms that regulate voltage-gated conductances within the spine but do not
      alter the properties or numbers of synaptic glutamate receptors.

PMID- 17224407
TI  - Persistence of long-term memory storage requires a late protein synthesis- and
      BDNF- dependent phase in the hippocampus.
AB  - Persistence is the most characteristic attribute of long-term memory (LTM). To
      understand LTM, we must understand how memory traces persist over time despite
      the short-lived nature and rapid turnover of their molecular substrates. It is
      widely accepted that LTM formation is dependent upon hippocampal de novo protein
      synthesis and Brain-Derived Neurotrophic Factor (BDNF) signaling during or early
      after acquisition. Here we show that 12 hr after acquisition of a one-trial
      associative learning task, there is a novel protein synthesis and BDNF-dependent
      phase in the rat hippocampus that is critical for the persistence of LTM storage.
      Our findings indicate that a delayed stabilization phase is specifically required
      for maintenance, but not formation, of the memory trace. We propose that memory
      formation and memory persistence share some of the same molecular mechanisms and
      that recurrent rounds of consolidation-like events take place in the hippocampus
      for maintenance of the memory trace.

PMID- 17224409
TI  - A magnitude code common to numerosities and number symbols in human intraparietal
      cortex.
AB  - Activation of the horizontal segment of the intraparietal sulcus (hIPS) has been
      observed in various number-processing tasks, whether numbers were conveyed by
      symbolic numerals (digits, number words) or by nonsymbolic displays (dot
      patterns). This suggests an abstract coding of numerical magnitude. Here, we
      critically tested this hypothesis using fMRI adaptation to demonstrate notation
      independent coding of numerical quantity in the hIPS. Once subjects were adapted
      either to dot patterns or to Arabic digits, activation in the hIPS and in frontal
      regions recovered in a distance-dependent fashion whenever a new number was
      presented, irrespective of notation changes. This remained unchanged when
      analyzing the hIPS peaks from an independent localizer scan of mental
      calculation. These results suggest an abstract coding of approximate number
      common to dots, digits, and number words. They support the idea that symbols
      acquire meaning by linking neural populations coding symbol shapes to those
      holding nonsymbolic representations of quantities.

PMID- 17224408
TI  - Neuronal oscillations and multisensory interaction in primary auditory cortex.
AB  - Recent anatomical, physiological, and neuroimaging findings indicate multisensory
      convergence at early, putatively unisensory stages of cortical processing. The
      objective of this study was to confirm somatosensory-auditory interaction in A1
      and to define both its physiological mechanisms and its consequences for auditory
      information processing. Laminar current source density and multiunit activity
      sampled during multielectrode penetrations of primary auditory area A1 in awake
      macaques revealed clear somatosensory-auditory interactions, with a novel
      mechanism: somatosensory inputs appear to reset the phase of ongoing neuronal
      oscillations, so that accompanying auditory inputs arrive during an ideal, high
      excitability phase, and produce amplified neuronal responses. In contrast,
      responses to auditory inputs arriving during the opposing low-excitability phase
      tend to be suppressed. Our findings underscore the instrumental role of neuronal
      oscillations in cortical operations. The timing and laminar profile of the
      multisensory interactions in A1 indicate that nonspecific thalamic systems may
      play a key role in the effect.

PMID- 17224410
TI  - Notation-dependent and -independent representations of numbers in the parietal
      lobes.
AB  - It is a commonly held view that numbers are represented in an abstract way in
      both parietal lobes. This view is based on failures to find differences between
      various notational representations. Here we show that by using relatively smaller
      voxels together with an adaptation paradigm and analyzing subjects on an
      individual basis it is possible to detect specialized numerical representations.
      The current results reveal a left/right asymmetry in parietal lobe function. In
      contrast to an abstract representation in the left parietal lobe, the numerical
      representation in the right parietal lobe is notation dependent and thus includes
      nonabstract representations. Our results challenge the commonly held belief that
      numbers are represented solely in an abstract way in the human brain.

PMID- 17224411
TI  - Malformation rate and sex ratio in 412 children conceived with epididymal or
      testicular sperm.
AB  - BACKGROUND: Follow-up studies of children conceived after ICSI using epididymal
      or testicular sperm are important due to a still more extensive use of immature
      male germ cells for ICSI. It is, however, difficult to evaluate the potential
      risks of malformations of children born after ICSI, overcoming the natural
      fertilization processes, due to methodological limitations. METHODS: Follow-up
      study including all children born in Denmark and Norway following ICSI in
      Denmark, using epididymal or testicular sperm, was done. A questionnaire was sent
      to the parents between 3 months and 7 years after delivery. RESULTS: Of 341
      couples, 329 returned the questionnaire giving a response rate of 96.5%. The
      study included 412 children, 225 girls and 187 boys, giving a sex ratio
      (males/males + females) of 45.4% compared with 53.1% in Danish children conceived
      after conventional IVF without ICSI (P < 0.005). Among a total of 14 (3.4%; 95%
      confidence interval (CI): 1.9%-5.7%) major malformations, three boys with
      hypospadias were the most remarkable finding (1.6%; 95% CI: 0.33-4.7%).
      CONCLUSIONS: An increased frequency of hypospadias in the male offsprings was
      seen compared with the general population. Apart from this, no increased major
      malformation rate was detected in ICSI children conceived with epididymal or
      testicular sperm when compared with malformation rates for IVF or spontaneously
      conceived children reported in the literature. The sex ratio was significantly
      lower for ICSI children conceived with epididymal or testicular sperm when
      compared with children conceived with conventional IVF.

PMID- 17224412
TI  - Emergence of ArmA and RmtB aminoglycoside resistance 16S rRNA methylases in
      Belgium.
AB  - OBJECTIVES: 16S rRNA methylase-mediated high-level resistance to aminoglycosides
      has been reported recently in clinical isolates of Gram-negative bacilli only
      from a limited number of countries. This study was conducted to investigate the
      occurrence of this type of resistance in clinical isolates of Enterobacteriaceae
      from two Belgian hospitals and the characteristics of the strains. METHODS: We
      screened for high-level gentamicin, tobramycin and amikacin resistance in
      clinical isolates of Enterobacteriaceae consecutively collected between 2000 and
      2005 at two laboratories by PCR for the armA, rmtA and rmtB 16S rRNA methylase
      genes. The beta-lactamase presence in the strains was also determined by
      phenotypic and genotypic methods. RESULTS: Overall armA genes were detected in 18
      Klebsiella pneumoniae, Escherichia coli, Enterobacter aerogenes, Enterobacter
      cloacae and Citrobacter amalonaticus whereas rmtB was detected in a single E.
      coli isolate. The rmtA gene was not found. All 16S rRNA methylase-bearing strains
      produced extended-spectrum beta-lactamases (ESBLs), predominantly type CTX-M-3,
      as well as various types of beta-lactamases. In the majority of the strains, the
      armA gene was carried by conjugative plasmids of the IncL/M incompatibility group
      whereas rmtB was borne by an IncFI plasmid. CONCLUSIONS: This is the first report
      of the emergence of 16S rRNA methylases in Enterobacteriaceae in Belgium. The
      rapid spread of multidrug-resistant isolates producing both ESBLs and 16S rRNA
      methylases raises clinical concern and may become a major therapeutic threat in
      the future.

PMID- 17224413
TI  - Efflux-mediated resistance to florfenicol and/or chloramphenicol in Bordetella
      bronchiseptica: identification of a novel chloramphenicol exporter.
AB  - OBJECTIVES: Twenty florfenicol- and/or chloramphenicol-resistant Bordetella
      bronchiseptica isolates of porcine and feline origin were investigated for the
      presence of floR and cml genes and their location on plasmids. METHODS: The B.
      bronchiseptica isolates were investigated for their susceptibility to
      antimicrobial agents by broth micro- or macrodilution and for their plasmid
      content. Hybridization experiments and PCR assays were conducted to identify
      resistance genes. Transformation and conjugation studies were performed to show
      their transferability. Representatives of both types of genes including their
      flanking regions were sequenced. Moreover, inhibitor studies with the efflux pump
      inhibitor Phe-Arg-beta-naphthylamide (PAbetaN) were performed. RESULTS: The gene
      floR was found in the chromosomal DNA of 9 of the 18 florfenicol/chloramphenicol
      resistant isolates. Sequence analysis revealed that the deduced FloR protein
      sequence differed by a single amino acid exchange from FloR of Vibrio cholerae. A
      chloramphenicol-resistant, but florfenicol-susceptible isolate carried a novel
      plasmid-borne cml gene, designated cmlB1. The CmlB1 protein revealed only 73.8
      76.5% identity to known CmlA proteins. The gene cmlB1 was not part of a gene
      cassette. The results of inhibitor studies with PAbetaN suggested that a so-far
      unidentified efflux system might play a role in phenicol resistance of the
      remaining florfenicol- and/or chloramphenicol-resistant isolates. CONCLUSIONS:
      This is to the best of our knowledge the first report of a floR gene in B.
      bronchiseptica isolates. The identification of the first member of a new subclass
      of cml genes, cmlB1 from B. bronchiseptica, extends our knowledge on specific
      chloramphenicol exporters.

PMID- 17224415
TI  - Acute management of sudden cardiac death in adults based upon the new CPR
      guidelines.
AB  - PURPOSE OF THE REVIEW: The aim of this article is to provide a comprehensive
      description of interventions that can improve outcomes in adults with sudden
      cardiac death. The new American Heart Association 2005 Guidelines introduced a
      number of changes for the initial management of cardiorespiratory arrest based on
      new data that accumulated over the last 5 years. ACUTE MANAGEMENT OF SUDDEN
      CARDIAC DEATH: Appropriate interventions targeting the three phases of
      cardiopulmonary resuscitation (CPR) (electrical, circulatory, and metabolic)
      should be implemented. Early defibrillation in early witnessed arrest with one
      shock is very effective and can improve survival outcomes. When resuscitation
      efforts are delayed and CPR is performed by paramedics, 2 min of CPR before shock
      is recommended. Emphasis has been placed on fast and forceful continuous
      compressions with minimal interruptions, adequate decompression, and decrease in
      the rate of ventilations to 8-10/min for intubated patients with two rescuers and
      a universal increase in compression to ventilation ratio to 30:2 for lone
      rescuers. Mechanical adjuncts to improve circulation have been adapted in the
      recommendations. The inspiratory impedance threshold device that enhances
      negative intrathoracic pressure and improves venous preload has been recommended
      for application in intubated and bag-mask ventilated patients. Owing to the
      difficulty of endotracheal intubation, airway management devices (Combitube and
      Laryngeal Mask Airway) can be used as alternatives with minimal extra training.
      CONCLUSION: The new guidelines for CPR have focused on early defibrillation,
      uninterrupted compressions, complete decompression, fewer ventilations, and
      simplification and uniformity of the process.

PMID- 17224416
TI  - Wave similarity of human ventricular fibrillation from bipolar electrograms.
AB  - AIMS: The aim of this report was to review existing techniques for assessment of
      directionality in fibrillation and to describe the concept of wave similarity
      analysis in human VF. METHODS: We applied a technique called wave similarity
      analysis to bipolar electrograms to study directionality during various rhythms
      (sinus rhythm, ventricular tachycardia and ventricular fibrillation) in humans.
      This technique uses the barycentre to determine the activation time and a
      similarity index is calculated using a technique described previously for AF
      studies. RESULTS: We show here that using the wave similarity concept it is
      possible to recognize myocardial regions that are activated from multiple
      directions and differentiate those areas from regions that are activated by wave
      fronts in similar direction or at the exact mirror angle in ventricular
      fibrillation. CONCLUSIONS: Wave similarity analysis provides a tool for assessing
      directional organization in human VF. This analysis of directional organization
      may have implications for the study of mechanisms of VF in the clinical arena.

PMID- 17224418
TI  - International study on syncope of uncertain aetiology 3 (ISSUE 3): pacemaker
      therapy for patients with asystolic neurally-mediated syncope: rationale and
      study design.
AB  - AIM: To assess the effectiveness of pacing therapy for preventing syncope
      recurrence in patients with a high probability of cardio-inhibitory neurally
      mediated syncope (NMS). METHODS:  STUDY DESIGN: Multi-centre, prospective, double
      blind, randomized placebo-controlled study. INCLUSION CRITERIA: Eligible patients
      are at least 40 years of age and have suffered, in the prior 2 years, > or = 3
      syncope episodes of suspected NMS (with the exception of carotid sinus syndrome),
      which is considered by the attending physician to have a severe clinical
      presentation requiring treatment initiation. Patients with positive and negative
      tilt testing are included. EXCLUSION CRITERIA: Patients with one or more of the
      following are excluded: carotid sinus syndrome; suspected or definite heart
      disease and high likelihood of cardiac syncope; symptomatic orthostatic
      hypotension diagnosed by standing blood pressure measurement; loss of
      consciousness different from syncope (e.g. epilepsy, psychiatric, metabolic, drop
      attack, TIA, intoxication, cataplexy); subclavian steal syndrome. STUDY PROTOCOL:
      Eligible patients receive an Implantable Loop Recorder and are followed till the
      first documented syncopal recurrence or a significant asystolic event. Those
      patients who have an asystolic pause (sinus arrest or AV block) > 6 s or a
      syncopal asystolic pause > or = 3 s receive a dual-chamber pacemaker implantation
      and are randomized to active therapy (Pm ON) or to placebo therapy (Pm OFF). End
      points: Primary end-point is the first syncope recurrence after pacemaker
      implant. Sample size and duration: A maximum of 710 patients are to be enrolled
      during an anticipated period of 2 years to allow randomization of 60 patients in
      the Pm ON arm and 60 in the Pm OFF arm (total 120).

PMID- 17224417
TI  - Psychological implications of ICD implantation in a New Zealand population.
AB  - AIMS: Previous studies have raised concerns about high levels of anxiety and
      depression in implanted cardioverter-defibrillator patients, and suggested that
      adverse psychological outcomes have been related to delivered therapy, age, and
      gender. This study aimed to assess the prevalence of anxiety and depression and
      to analyse quality-of-life in a New Zealand patient group. METHODS AND RESULTS:
      We questioned 46 ICD and 49 pacemaker patients regarding device and treatment
      satisfaction, depression, anxiety (Hospital Anxiety and Depression Scale), and
      quality-of-life (SF 36). The prevalence of clinical depression and anxiety in the
      ICD group was 7 and 13%, respectively, and did not differ from the pacemaker
      group. ICD patients mean anxiety and depression scores did not differ from the
      pacemaker group, although more ICD patients had subclinical levels of anxiety.
      Quality-of-life scores were normal for all ICD patients with respect to both
      mental and physical component scores, and not different from the pacemaker group.
      Anxiety, depression, and quality-of-life scores were unrelated to time from
      implantation, delivered therapy, age, or gender. Overall, 93% of the ICD patients
      thought their device was worthwhile. CONCLUSION: We found a lower than expected
      level of anxiety and depression in ICD patients, and suggest that this may be due
      in part to the small team approach adopted locally in the follow-up of this
      patient group.

PMID- 17224419
TI  - Pacing for neurally mediated syncope: is placebo powerless?
AB  - BACKGROUND: After two recent controlled trials failed to prove superiority of
      cardiac pacing over placebo in patients affected by neurally mediated syncope, a
      widely accepted opinion is that cardiac pacing therapy is not very effective and
      that a strong placebo effect exists. AIM: To measure the effect of placebo pacing
      therapy. METHOD AND RESULTS: We compared the recurrence rate of syncope during
      placebo vs. no treatment in controlled trials of drug or pacing therapy. Syncope
      recurred in 38% of 252 patients randomized to placebo pooled from five trials vs.
      34% of 881 patients randomized to no treatment pooled from eight trials. The
      corresponding recurrence rate with active cardiac pacing was 15% in 203 patients
      from six trials. CONCLUSIONS: Placebo is not an effective therapy for neurally
      mediated syncope. Different selection criteria in patients who are candidates for
      cardiac pacing-for example, presence, absence, or severity of the
      cardioinhibitory reflex may separate positive from negative trials.

PMID- 17224420
TI  - Evidence of left ventricular dyssynchrony resulting from right ventricular pacing
      in patients with severely depressed left ventricular ejection fraction.
AB  - AIMS: Cardiac resynchronization therapy (CRT) has recently emerged as an
      effective treatment for patients with moderate-to-severe systolic heart failure
      and left bundle branch block (LBBB). Right ventricular pacing (RVP) leads to an
      LBBB-like pattern in the electrocardiogram. The aim of this study was to evaluate
      the frequency of ventricular mechanical dyssynchrony in patients induced by RVP.
      METHODS AND RESULTS: The study included 33 patients with a conventional single or
      dual chamber pacemaker, 18 with ejection fraction (EF) > 35% and 15 with EF < or
      = 35%. In all patients, an intrinsic rhythm without intraventricular conduction
      delay (QRS < or = 120 ms) was present without RVP. Two-dimensional and Doppler
      echocardiographic criteria for mechanical dyssynchrony [aortic pre-ejection delay
      (APE), interventricular mechanical delay (IVMD), delayed activation of the
      posterior left ventricular wall (PD), septal-to-posterior wall motion delay
      (SPWMD)] were evaluated in all patients with and without RVP. QRS duration showed
      no difference between the two EF-groups without RVP (93 +/- 10 vs. 96 +/- 9 ms),
      but was significantly longer in patients with low EF with RVP (152 +/- 18 vs. 181
      +/- 18 ms; P < 0.001). In patients with EF > 35%, only APE was slightly prolonged
      by RVP (111 +/- 20 vs. 129 +/- 17 ms; P = 0.03), whereas in patients with EF < or
      = 35% marked pathological differences in APE (118 +/- 29 vs. 169 +/- 24 ms; P <
      0.001), IVMD (22 +/- 17 vs. 58 +/- 14 ms; P < 0.001), SPWMD (103 +/- 28 vs. 125
      +/- 29 ms; P = 0.004), and PD (-21 +/- 25 vs. - 39 +/- 25 ms; P = 0.005) were
      found. A significant correlation between QRS duration and mechanical ventricular
      dyssynchrony was only found for two echocardiographic parameters (IVMD, APE) with
      RVP. CONCLUSION: In patients with a conventional pacemaker, mechanical
      dyssynchrony with RVP was shown exceptionally in patients with preserved or
      moderately depressed systolic left ventricular (LV) function, but in nearly all
      patients with severely depressed systolic LV function. These patients might
      benefit from CRT when frequent RVP is required.

PMID- 17224422
TI  - Biventricular pacing and transmural dispersion of the repolarization.

PMID- 17224421
TI  - Left ventricular electromechanical delay in patients with heart failure and
      normal QRS duration and in patients with right and left bundle branch block.
AB  - AIMS: We sought to define the reference values of intra-left ventricular (LV)
      electromechanical delay (EMD), and to assess the prevalence (and pattern) of
      intra-LV dyssynchrony in patients with heart failure (HF) and normal QRS and in
      patients with right and left bundle branch block. METHODS AND RESULTS: We used
      tissue Doppler imaging echocardiography and a six-LV wall model to study LV EMD
      in 103 patients [41 with HF and normal QRS, 22 with right bundle branch block
      (RBBB), and 40 with left bundle branch block (LBBB)], and in 59 controls. In
      controls, the median intra-LV EMD was 17 ms, (inter-quartile range 13-30); 95% of
      controls had a value < or =41 ms. Patients showed a longer intra-LV EMD than
      controls: 33 ms (20-57) in patients with normal QRS, 32 ms (23-50) in RBBB
      patients, and 50 ms (30-94) in LBBB patients. Intra-LV dyssynchrony (defined as
      intra-LV EMD >41 ms) was present in 39, 36, and 60% of the patients,
      respectively. On average, HF patients showed the same pattern of activation as
      controls, from the septum to the posterior wall, but activation times were
      significantly prolonged. In RBBB patients the activation sequence was directed
      from inferior to anterior and in LBBB from anterior to inferior wall.
      CONCLUSIONS: Left ventricular dyssynchrony was present in several patients with
      HF and normal QRS, and in patients with RBBB; conversely, 40% of LBBB patients
      showed values of LV EMD within the normal range. Left ventricular activation
      sequence was different between groups. Assessment of LV synchronicity by means of
      imaging techniques may be more important than QRS duration or morphology in
      selecting patients for cardiac resynchronization treatment.

PMID- 17224423
TI  - Regression of dilated-hypokinetic hypertrophic cardiomyopathy by biventricular
      cardiac pacing.
AB  - The evolution of hypertrophic cardiomyopathy (HCM) towards dilatation and
      hypokinesis is an increasingly recognized complication with a high incidence of
      adverse outcomes, including sudden cardiac death, requiring defibrillator
      implantation and cardiac transplantation. It is generally regarded as the
      irreversible 'burnt-out' end-stage manifestation of HCM. We report one of the
      first cases of profound regression of the dilated-hypokinetic state by the
      application of biventricular pacing and cardiac resynchronization therapy (CRT).
      Reviewing the literature on the role of pacing in HCM and the energetic rationale
      for CRT in HCM prompts us to suggest that further systematic studies are needed
      urgently to assess the role of CRT in HCM variants.

PMID- 17224424
TI  - Effects of exercise training on heart rate and QT interval in healthy young
      individuals: are there gender differences?
AB  - AIMS: The aim of the present study was to assess the effects of exercise training
      on heart rate, QT interval, and on the relation between ventricular
      repolarization and heart rate in men and women. METHODS AND RESULTS: A 24 h
      Holter recording was obtained in 80 healthy subjects (40 males) who differed for
      the degree of physical activity. Trained individuals showed a lower heart rate
      and a higher heart rate variability than sedentary subjects, independent of the
      gender difference in basal heart rate. Mean 24 h QTc was similar in trained and
      non-trained men, while a significant difference was observed between trained and
      non-trained women. Exercise training reduced the QT/RR slope in both genders.
      This effect on the QT/RR relation was more marked in women; in fact, the gender
      difference in the ventricular repolarization duration at low heart rate observed
      in sedentary subjects was no longer present among trained individuals.
      CONCLUSION: The results of this study suggest that the cardiovascular response to
      exercise training may be different in men and women. Women may benefit more from
      interventions aimed to increase physical activity as a tool for prevention of
      cardiovascular morbidity and mortality.

PMID- 17224426
TI  - A novel catheter for simultaneous angiography of ipsilateral pulmonary veins.
AB  - We designed a novel catheter for simultaneous angiography of ipsilateral
      pulmonary veins (PVs), so that the catheter tip with side holes can be introduced
      into the inferior PVs and a second curve with side holes into the superior PVs.
      The simultaneous angiogram of the ipsilateral PVs, using this novel catheter,
      reveals more clearly the PV ostium to antrum, because simultaneous injection of
      contrast medium into two adjacent PVs reduces the dilution of contrast medium by
      blood flow through these veins.

PMID- 17224427
TI  - Visualization of the oesophagus in relation to the left atrium: an alternative
      concept.

PMID- 17224428
TI  - Drug-induced pericarditis mimicking Brugada syndrome.
AB  - Brugada syndrome (BS) is associated with sudden cardiac death in patients with a
      structurally normal heart. The ECG pattern of BS has also been described in
      patients with myocardial abnormalities. Cardiac hypersensitivity and
      myopericarditis have been reported during long-term treatment with mesalazine. We
      report the case of a man, treated with mesalazine for Crohn's disease who
      developed drug-induced pericarditis. The ECG showed a coved ST-segment elevation
      in the right precordial leads V1-V3, a pattern mimicking BS. The ECG normalized
      in a few days after mesalazine withdrawal and the follow-up was uneventful. The
      ECG remained normal. Two ajmaline tests were both negative and ruled out the
      diagnosis of BS. This observation illustrates that a coved ST-segment elevation
      in the right precordial leads should not be, systematically, regarded as a marker
      of a specific syndrome, but may also reflect a common electrical manifestation of
      abnormalities in the right ventricle or pericardium.

PMID- 17224430
TI  - Brachiocephalic vein perforation on three-dimensional computed tomography.

PMID- 17224429
TI  - Usefulness of mechanical transvenous dilation and location of areas of adherence
      in patients undergoing coronary sinus lead extraction.
AB  - AIMS: Few data have been currently reported on the outcome of coronary sinus (CS)
      lead removal, particularly using mechanical dilation (MD). We aimed to evaluate
      feasibility, safety, and effectiveness of CS lead extraction, focusing on MD
      usefulness, in the event that lead traction (LT) was ineffective. METHODS AND
      RESULTS: We studied 37 consecutive patients (30 males, mean age 68.1, range 52
      80), who underwent left ventricle (LV) pacing lead removal; the indication for
      extraction was local infection in 16 patients (43.3%), sepsis in 11 patients
      (29.7%), and lead malfunction in 10 patients (27%). The procedure was first
      attempted by LT, followed, if unsuccessful, by MD using polypropylene sheaths.
      All CS leads (time from implant 19.5 +/- 16.5, range 2-84 months) were
      successfully removed; LT was effective (LT group) in 27 patients (73%) and
      ineffective in 10 patients (27%), for whom MD was necessary (MD group). There
      were no major complications. The areas of adherence were in the CS in only one
      patient. No differences were noted in the data analysed between LT and MD groups;
      in particular, time from implant was similar in the two groups (MD vs. LT group:
      17 +/- 8.9 vs. 20.4 +/- 18.6 months; P = ns). CONCLUSION: Our study suggests that
      CS leads, after medium-term implantation, can be effectively and safely removed
      using MD with polypropylene sheaths, in the case of unsuccessful LT. No pre
      operative elements predictive of LT failure could be identified. Areas of
      adherence were rarely located in the CS or its tributaries.

PMID- 17224431
TI  - Unusual VDD-pacing.
AB  - The case of an 80-year-old woman who underwent permanent VDD-pacemaker
      implantation for recurrent syncope in the presence of second-degree type 2 AV
      block is reported. During follow-up, low atrial sensing with AV-synchrony of only
      58-73% was noted. Four years after the pacemaker implantation, the patient was
      hospitalized for non-cardiac reasons and the chest radiograph showed displacement
      of the atrial dipole into the right ventricular outflow tract (RVOT). It is
      hypothesized that AV-synchrony was maintained by left atrial sensing due to the
      anatomic proximity of the RVOT to the left atrial appendage.

PMID- 17224433
TI  - An isokinetic eccentric programme for the management of chronic lateral
      epicondylar tendinopathy.
AB  - BACKGROUND: Lateral epicondylitis represents a frequent overuse injury. In spite
      of many conservative treatment procedures, prolonged symptoms and relapse are
      frequently observed. OBJECTIVE: To compare the outcome of patients performing an
      isokinetic eccentric training with that of age-, gender-, activity-matched
      patients receiving a non-strengthening classical rehabilitation. METHODS: Ninety
      two patients with unilateral chronic lateral epicondylar tendinopathy (mean
      duration of symptoms 8+/-3 months) were assigned either to a control group (n =
      46) or to an eccentrically trained group (n = 46). The control group underwent a
      passive standardised rehabilitation programme that excluded strengthening
      exercises. In addition to this programme, the trained group also performed
      eccentric exercises based on the repetitive lengthening of the active musculo
      tendinous unit. The latter exercises started with submaximal contraction
      intensity and slow speed movement. Modalities were progressively intensified
      (increase in intensity contraction and speed movement) over a long period of
      treatment. Programme effectiveness was assessed through pain score evaluation, a
      disability questionnaire, muscle strength measurement and ultrasonographic
      examination. RESULTS: Compared to the non-strengthening control group, the
      following observations were made in the eccentrically trained group: (1) a
      significantly more marked reduction of pain intensity, mainly after one month of
      treatment; (2) an absence of strength deficit on the involved side through
      bilateral comparison for the forearm supinator and wrist extensor muscles; (3) an
      improvement of the tendon image as demonstrated by decreasing thickness and a
      recovered homogenous tendon structure; and (4) a more marked improvement in
      disability status during occupational, spare time and sports activities.
      CONCLUSION: These results highlight the relevance of implementing isokinetic
      adapted eccentric training in the management of chronic lateral epicondylar
      tendinopathy.

PMID- 17224434
TI  - Effects of warm-up and precooling on endurance performance in the heat.
AB  - OBJECTIVE: To examine the effects of different thermoregulatory preparation
      procedures (warm-up (WU), precooling (PC), control (C)) on endurance performance
      in the heat. METHODS: 20 male subjects completed three treadmill runs to
      exhaustion (5 days apart). In each session, all subjects performed an incremental
      running test after WU (20 min at 70% maximum heart rate (HR)), after PC (wearing
      a cooling vest (0 degrees C-5 degrees C) for 20 min at rest) or without
      particular preparation (C). After a 5-min break, the exercise protocol commenced
      at a workload of 9 km/h and was increased by 1 km/h every 5 min until the point
      of volitional fatigue. Running performance, HR, blood lactate concentration,
      tympanic temperature and skin temperature were measured in each trial. RESULTS:
      In the PC condition, the running performance (32.5 (5.1) min; mean (SD)) was
      significantly (p<0.05) higher than in WU (26.9 (4.6) min) and in C conditions
      (30.3 (4.3) min). During the first 30 min of testing, HR, tympanic temperature
      and skin temperature were significantly (p<0.05) lower after PC than after WU.
      There were no significant differences in lactate concentration; however, there
      was a trend to lower values after WU. CONCLUSIONS: The use of an ice-cooling vest
      for 20 min before exercising improved running performance, whereas the 20 min WU
      procedure had a distinctly detrimental effect. Cooling procedures including
      additional parts of the body such as the head and the neck might further enhance
      the effectiveness of PC measures.

PMID- 17224435
TI  - Impact of Ramadan on physical performance in professional soccer players.
AB  - OBJECTIVE: Ramadan is a period of daylight abstention from liquid or solid
      nutrients. As sports continue to be scheduled, an understanding of the effects of
      Ramadan on Muslim athletes is warranted. DESIGN: Two Algerian professional soccer
      teams (55 men) were studied. Field tests of physical and soccer performance were
      collected before, at the end and 2 weeks after Ramadan in 2004. Players were
      queried on sleeping habits and personal perception of training and match
      performance. SETTING: Field setting at club training ground. MAIN OUTCOME
      MEASURES: Performance on fitness and skill tests. RESULTS: Performance declined
      significantly (p<0.05) for speed, agility, dribbling speed and endurance, and
      most stayed low after the conclusion of Ramadan. Nearly 70% of the players
      thought that their training and performance were adversely affected during the
      fast. CONCLUSIONS: The phase shift of food intake and disruption of sleep
      patterns affect actual and perceived physical performance. Islamic athletes need
      to explore strategies that will maximise performance during Ramadan.

PMID- 17224436
TI  - Injuries in Swedish skydiving.
AB  - OBJECTIVE: To create a basis for prevention of modern skydiving injuries. DESIGN:
      Descriptive epidemiological study. SETTING: National total material. PATIENTS:
      Data on all reported injury events (n = 257) in Swedish skydiving 1999-2003
      (total 539,885 jumps) were retrieved from the Swedish Parachute Association. Non
      fatally injured skydivers were sent a questionnaire asking for event and injury
      details (response rate 89%), and supplementary hospital records were retrieved
      for the most serious injuries (n = 85). Human, equipment and environmental
      factors were assessed for risk. MAIN OUTCOME MEASUREMENTS: Frequency and severity
      of injuries. RESULTS: Incidence of non-fatal injury events was 48 per 100,000
      jumps. The lower extremities, spine and shoulders were important regions of
      injury. The most serious injuries were experienced by licensed skydivers, but
      students in training had a higher injury rate and more often left the sport
      because of the injury. Of two student-training systems, one had an incidence less
      than half that of the other. CONCLUSIONS: A basis for prevention was created,
      showing a potential for reduction of frequency and severity of injuries with
      training and technical interventions.

PMID- 17224437
TI  - Relationship between landing strategy and patellar tendinopathy in volleyball.
AB  - OBJECTIVE: The aetiology of patellar tendinopathy (jumper's knee) remains
      unclear. To see whether landing strategy might be a risk factor for the
      development of this injury, this study examined whether landing dynamics from
      drop jumps differed among healthy volleyball players (CON) and volleyball players
      with a jumper's knee. The patients with jumper's knee were divided into an
      asymptomatic group with a previous jumper's knee (PJK) and a symptomatic group
      with a recent jumper's knee (RJK). METHODS: Inverse dynamics analyses were used
      to estimate lower extremity joint dynamics from 30, 50 and 70 cm drop jumps in
      the three groups (CON, n = 8; PJK, n = 7; RJK, n = 9). A univariate repeated
      measures analysis of variance was used to compare the different landing
      techniques. RESULTS: Data analysis of the landing dynamics revealed that PJK
      showed higher knee angular velocities (p<0.01), and higher ankle plantar flexion
      moment loading rate (p<0.01). Furthermore, strong tendencies of higher loading
      rate of vertical ground reaction force (p = 0.05) and higher knee extensor moment
      loading rate (p = 0.08) were found compared with CON. Higher values for peak knee
      moment, peak knee power and knee work (all p<0.01) were found for CON compared
      with RJK. The comparison of the two jumper's knee groups yielded higher knee
      angular velocities (p<0.01), together with higher ankle plantar flexion and knee
      extensor moment loading rate (p<0.01 and p<0.05, respectively). CONCLUSION: Where
      RJK used a landing technique to avoid high patellar tendon loading, PJK used a
      stiffer landing strategy, which may be a risk factor in the development of
      patellar tendinopathy.

PMID- 17224438
TI  - Effects of a maximal exercise test on neurocognitive function.
AB  - OBJECTIVE: To examine the effects of a maximal exercise test on cognitive
      function in recreational athletes. DESIGN: A repeated-measures design was used to
      compare baseline with post-cognitive function and fatigue symptoms after a
      maximal exercise test. SETTING: Division 1 American Midwestern University,
      (Michigan State University, Michigan, USA). PARTICIPANTS: 102 male and female
      recreational athletes. INTERVENTION: Participants in the experimental group (n =
      54) were asked to perform a maximal treadmill exercise test to maximal oxygen
      uptake (VO2 max). Participants in the control group were asked to rest for 15
      min. MAIN OUTCOME MEASUREMENTS: All participants were administered a
      neuropsychological test battery called Immediate Post-Concussion Assessment and
      Cognitive Testing (ImPACT) before and after exercise to measure neurocognitive
      function and fatigue symptoms. RESULTS: Results revealed a significant group
      (control, experimental) x time (baseline, post-test 1, post-test 2) interaction
      for verbal memory composite scores (p = 0.025). Specifically, verbal memory
      composite scores decreased in the experimental group from baseline to post-test 1
      (p = 0.00). These values returned to baseline 3 days after the VO2 max test (p =
      0.00). Further analysis on verbal memory composite scores demonstrated
      significant differences on immediate recall memory (p = 0.00) and delayed recall
      memory (p = 0.00). No significant differences were observed for visual memory (p
      = 0.54), motor processing speed (p = 0.68) and reaction time (p = 0.44) composite
      scores between the experimental and control groups. CONCLUSION: The results of
      this study suggest that a maximal exercise test attenuated a limiting effect on
      cognitive function. When utilising a neuropsychological test battery to evaluate
      a patient who has sustained a head injury, the test should not be administered
      immediately after a practice or a game session.

PMID- 17224439
TI  - Circumflex femoral vein thrombosis misinterpreted as acute hamstring strain.
AB  - The case of a 24-year-old female professional, long-distance runner who presented
      with acute proximal posterior thigh pain is reported. History and clinical
      findings were consistent with acute hamstring strain but MRI demonstrated
      circumflex femoral vein thrombosis. This is the first case of proximal posterior
      thigh pain caused by circumflex femoral vein thrombosis reported in the
      literature. Doctors dealing with sports injuries should be aware of this clinical
      entity that mimics hamstring strain.

PMID- 17224440
TI  - Microwave hyperthermia treatment increases heat shock proteins in human skeletal
      muscle.
AB  - OBJECTIVE: To test the hypothesis that microwave hyperthermia treatment (MHT)
      increases heat shock proteins (HSPs) in the human vastus lateralis muscle.
      METHODS: Four untrained healthy male volunteers participated in this study. The
      lateral side of the thigh of one leg (heated leg) was heated with a microwave
      generator (2.5 GHz, 150 W) for 20 min. At 1 day after the MHT, a muscle sample
      was taken from the heated leg. A control sample was taken from the unheated leg
      on another day of the MHT. For both legs, HSP90, HSP72 and HSP27 levels were
      compared. RESULTS: The HSP90, HSP72 and HSP27 levels in heated legs were
      significantly higher than those in control legs (p<0.05). CONCLUSIONS:
      Application of MHT can increase the levels of several HSPs in human skeletal
      muscle.

PMID- 17224441
TI  - Biomechanical analysis of the single-leg decline squat.
AB  - BACKGROUND: The single-leg squat on a 25 degrees decline board has been described
      as a clinical assessment tool and as a rehabilitation exercise for patients with
      patellar tendinopathy. Several assumptions have been made about its working
      mechanism on patellar load and patellofemoral forces, but these are not
      substantiated by biomechanical evaluations. AIM: To investigate knee moment and
      patellofemoral contact force as a function of decline angle in the single-leg
      squat. METHODS: Five subjects performed single-leg eccentric squats at decline
      angles of 0 degrees, 5 degrees, 10 degrees, 15 degrees, 20 degrees and 25 degrees
      (with/without a backpack of 10 kg), and 30 degrees on a board that was placed
      over a forceplate. Kinematic and forceplate data were recorded by the Optotrak
      system. Joint moments of ankle, knee and hip were calculated by two-dimensional
      inverse dynamics. RESULTS: Knee moment increased by 40% at decline angles of 15
      degrees and higher, whereas hip and ankle moment decreased. Maximum knee and
      ankle angles increased with steeper decline. With a 10 kg backpack at 25 degrees
      decline, the knee moment was 23% higher than unloaded. Both patellar tendon and
      patellofemoral forces increased with higher decline angles, but beyond 60
      degrees, the patellofemoral force rose steeper than the tendon force.
      CONCLUSIONS: All single-leg squats at decline angles >15 degrees result in 40%
      increase in maximum patellar tendon force. In knee flexions >60 degrees,
      patellofemoral forces increase more than patellar tendon forces. Higher tendon
      load can be achieved by the use of a backpack with extra weight.

PMID- 17224442
TI  - Change in the capability of reactive oxygen species production by neutrophils
      following weight reduction in female judoists.
AB  - OBJECTIVE: Athletes undergoing weight reduction are recognised as being more
      prone to infection. Few studies exist for athletes on the weight reduction
      mediated changes in neutrophil function and related activities such as reactive
      oxygen species (ROS) production capability, phagocytic activity (PA) and serum
      opsonic activity (SOA). METHODS: 16 Japanese female university judoists were
      examined in the early morning of the first day (pre-values) and the last day
      (post-values) of a 20-day pre-competition training period. Of the 16 subjects, 8
      needed to reduce weight (WR group) and the other 8 did not (control group). The
      parameters assessed were the neutrophil count, serum immunoglobulins and
      complements, myogenic enzymes, ROS production capability, PA and SOA. RESULTS:
      Comparing the post-values with the pre-values, ROS production significantly
      increased in both groups (p<0.01 for both). PA significantly decreased in the WR
      group (p<0.05); it also decreased in the control group but the decrease was not
      significant. SOA significantly increased in the control group (p<0.05), but
      showed no significant change in the WR group. CONCLUSIONS: The changes in the WR
      group were probably a direct consequence of the weight-reduction regimen coupled
      with the exercise regimen, suggesting that neutrophil parameters (ROS production,
      PA and SOA) had tended to deviate from their typical compensatory changes to
      maintain immune system homoeostasis.

PMID- 17224443
TI  - Near-fatal spontaneous hepatic rupture associated with anabolic androgenic
      steroid use: a case report.
AB  - Anabolic androgenic steroids are commonly used at high doses by bodybuilders and
      athletes to enhance physique and improve performance levels. We report a case of
      spontaneous hepatic rupture with life-threatening haemorrhage associated with a
      past history of anabolic steroid use.

PMID- 17224444
TI  - Characteristics of youth soccer players aged 13-15 years classified by skill
      level.
AB  - OBJECTIVE: To evaluate the growth, maturity status and functional capacity of
      youth soccer players grouped by level of skill. SUBJECTS: The sample included 69
      male players aged 13.2-15.1 years from clubs that competed in the highest
      division for their age group. METHODS: Height and body mass of players were
      measured and stage of pubic hair (PH) was assessed at clinical examination. Years
      of experience in football were obtained at interview. Three tests of functional
      capacity were administered: dash, vertical jump and endurance shuttle run.
      Performances on six soccer-specific tests were converted to a composite score
      which was used to classify players into quintiles of skill. Multiple analysis of
      covariance, controlling for age, was used to test differences among skill groups
      in experience, growth status and functional capacity, whereas multiple linear
      regression analysis was used to estimate the relative contributions of age, years
      of training in soccer, stage of PH, height, body mass, the height x weight
      interaction and functional capacities to the composite skill score. RESULTS: The
      skill groups differed significantly in the intermittent endurance run (p<0.05)
      but not in the other variables. Only the difference between the highest and
      lowest skill groups in the endurance shuttle run was significant. Most players in
      the highest (12 of 14) and high (11 of 14) skill groups were in stages PH 4 and
      PH 5. Pubertal status and height accounted for 21% of the variance in the skill
      score; adding aerobic resistance to the regression increased the variance in
      skill accounted for to 29%. In both regressions, the coefficient for height was
      negative. CONCLUSION: Adolescent soccer players aged 13-15 years classified by
      skill do not differ in age, experience, body size, speed and power, but differ in
      aerobic endurance, specifically at the extremes of skill. Stage of puberty and
      aerobic resistance (positive coefficients) and height (negative coefficient) are
      significant predictors of soccer skill (29% of the total explained variance),
      highlighting the inter-relationship of growth, maturity and functional
      characteristics of youth soccer players.

PMID- 17224445
TI  - The effect of cryotherapy on nerve conduction velocity, pain threshold and pain
      tolerance.
AB  - OBJECTIVES: To determine the impact of the application of cryotherapy on nerve
      conduction velocity (NCV), pain threshold (PTH) and pain tolerance (PTO). DESIGN:
      A within-subject experimental design; treatment ankle (cryotherapy) and control
      ankle (no cryotherapy). SETTING: Hospital-based physiotherapy laboratory.
      PARTICIPANTS: A convenience sample of adult male sports players (n = 23). MAIN
      OUTCOME MEASURES: NCV of the tibial nerve via electromyogram as well as PTH and
      PTO via pressure algometer. All outcome measures were assessed at two sites
      served by the tibial nerve: one receiving cryotherapy and one not receiving
      cryotherapy. RESULTS: In the control ankle, NCV, PTH and PTO did not alter when
      reassessed. In the ankle receiving cryotherapy, NCV was significantly and
      progressively reduced as ankle skin temperature was reduced to 10 degrees C by a
      cumulative total of 32.8% (p<0.05). Cryotherapy led to an increased PTH and PTO
      at both assessment sites (p<0.05). The changes in PTH (89% and 71%) and PTO (76%
      and 56%) were not different between the iced and non-iced sites. CONCLUSIONS: The
      data suggest that cryotherapy can increase PTH and PTO at the ankle and this was
      associated with a significant decrease in NCV. Reduced NCV at the ankle may be a
      mechanism by which cryotherapy achieves its clinical goals.

PMID- 17224446
TI  - Wireless connectivity for health and sports monitoring: a review.
AB  - This is a review of health and sports monitoring research that uses or could
      benefit from wireless connectivity. New, enabling wireless connectivity standards
      are evaluated for their suitability, and an assessment of current exploitation of
      these technologies is summarised. An example of the application is given,
      highlighting the capabilities of a network of wireless sensors. Issues of timing
      and power consumption in a battery-powered system are addressed to highlight the
      benefits networking can provide, and a suggestion of how monitoring different
      biometric signals might allow one to gain additional information about an athlete
      or patient is made.

PMID- 17224447
TI  - Caldendrin, a neuron-specific modulator of Cav/1.2 (L-type) Ca2+ channels.
AB  - EF-hand Ca2+-binding proteins such as calmodulin and CaBP1 have emerged as
      important regulatory subunits of voltage-gated Ca2+ channels. Here, we show that
      caldendrin, a variant of CaBP1 enriched in the brain, interacts with and
      distinctly modulates Cav1.2 (L-type) voltage-gated Ca2+ channels relative to
      other Ca2+-binding proteins. Caldendrin binds to the C-terminal IQ-domain of the
      pore-forming alpha1-subunit of Cav1.2 (alpha(1)1.2) and competitively displaces
      calmodulin and CaBP1 from this site. Compared with CaBP1, caldendrin causes a
      more modest suppression of Ca2+-dependent inactivation of Cav1.2 through a
      different subset of molecular determinants. Caldendrin does not bind to the N
      terminal domain of alpha11.2, a site that is critical for functional interactions
      of the channel with CaBP1. Deletion of the N-terminal domain inhibits CaBP1, but
      spares caldendrin modulation of Cav1.2 inactivation. In contrast, mutations of
      the IQ-domain abolish physical and functional interactions of caldendrin and
      Cav1.2, but do not prevent channel modulation by CaBP1. Using antibodies specific
      for caldendrin and Cav1.2, we show that caldendrin coimmunoprecipitates with
      Cav1.2 from the brain and colocalizes with Cav1.2 in somatodendritic puncta of
      cortical neurons in culture. Our findings reveal functional diversity within
      related Ca2+-binding proteins, which may enhance the specificity of Ca2+
      signaling by Cav1.2 channels in different cellular contexts.

PMID- 17224448
TI  - Phosphorylation of adult type Sept5 (CDCrel-1) by cyclin-dependent kinase 5
      inhibits interaction with syntaxin-1.
AB  - Increasing evidence implicates cyclin-dependent kinase 5 (Cdk5) in neuronal
      synaptic function. We searched for Cdk5 substrates in synaptosomal fractions
      prepared from mouse brains. Mass spectrometric analysis after two-dimensional SDS
      PAGE identified several synaptic proteins phosphorylated by Cdk5-p35; one protein
      identified was Sept5 (CDCrel-1). Although septins were isolated originally as
      cell division-related proteins in yeast, Sept5 is expressed predominantly in
      neurons and is implicated in exocytosis. We confirmed that Sept5 is
      phosphorylated by Cdk5-p35 in vitro and identified Ser17 of adult type Sept5
      (Sept5_v1) as a major phosphorylation site. We found that Ser17 of Sept5_v1 is
      phosphorylated in mouse brains. Coimmunoprecipitation from synaptosomal fractions
      and glutathione S-transferase-syntaxin-1A pulldown assays of Sept5_v1 expressed
      in COS-7 cells showed that phosphorylation of Sept5_v1 by Cdk5-p35 decreases the
      binding to syntaxin-1. These results indicate that the interaction of Sept5 with
      syntaxin-1 is regulated by the phosphorylation of Sept5_v1 at Ser17 by Cdk5-p35.

PMID- 17224449
TI  - UVA induces granzyme B in human keratinocytes through MIF: implication in
      extracellular matrix remodeling.
AB  - In a previous study, we have described that UVB induces granzyme B (GrB) in human
      keratinocyte cells, and that confers potent cellular cytotoxicity against various
      cellular models, including immune cells (Hernandez-Pigeon, H., Jean, C.,
      Charruyer, A., Haure, M. J., Titeux, M., Tonasso, L., Quillet-Mary, A., Baudouin,
      C., Charveron, M., and Laurent, G. (2006) J. Biol. Chem. 281, 13525-13532).
      Herein, we have found that, in contrast to UVB, UVA failed to enhance
      keratinocyte cellular cytotoxicity but was still able to trigger GrB production.
      We show that GrB is accumulated through a p38 MAPK-dependent transcriptional
      mechanism stimulated by redox-dependent migration inhibitory factor release.
      Moreover, GrB purified from UVA-treated cellular extracts was found to degrade
      fibronectin in vitro. Treatment with antisense oligonucleotide directed against
      GrB resulted in the inhibition of UVA-induced cell detachment and cell death and
      facilitated cell migration through fibronectin and vitronectin matrix upon UVA
      exposure. Altogether, these results suggest another function for GrB in the
      context of the UV response. Indeed, combined with our previous study, it appears
      that, whereas this enzyme mediates keratinocyte cellular cytotoxicity following
      UVB irradiation, GrB supports the capacity of keratinocyte to degrade
      extracellular matrix components following UVA irradiation. UV-mediated GrB
      production may thus have important consequences in photoaging and
      photocarcinogenesis.

PMID- 17224450
TI  - Physical association between neuropeptide FF and micro-opioid receptors as a
      possible molecular basis for anti-opioid activity.
AB  - Neuropeptide FF (NPFF) modulates the opioid system by exerting functional anti
      opioid activity on neurons, the mechanism of which is unknown. By using a model
      of SH-SY5Y cells, we recently postulated that anti-opioid activity likely takes
      place upstream from the signaling cascade, suggesting that NPFF receptors could
      block opioid receptors by physical interaction. In the present study,
      fluorescence techniques were used to monitor the physical association and the
      dynamic of NPFF2 and micro-opioid (MOP) receptors tagged with variants of the
      green fluorescent protein. Importantly, cyan fluorescent protein-tagged NPFF2
      receptors retained their capacity to antagonize opioid receptors. Fluorescence
      resonance energy transfer (FRET) and coimmunoprecipitation studies indicate that
      NPFF and MOP receptors are close enough to generate a basal FRET signal. The
      opioid agonist Tyr-D-Ala-Gly-NMe-Phe-Gly-ol disrupts by 20-30% this FRET signal,
      mainly because it concomitantly induces 40% internalization of receptors. In
      contrast, the NPFF analog 1DMe significantly increases by 10-15% the basal FRET
      signal, suggesting an association between both receptors. In addition, 1DMe
      reduces, by half, MOP receptor internalization, indicating that, besides a
      functional blockade of opioid receptors, the NPFF analog also inhibits their
      internalization. Finally, as a first report showing the modulation of the
      mobility of a G-protein-coupled receptor by another one, fluorescence recovery
      after photobleaching analysis reveals that 1DMe modifies the lateral diffusion of
      MOP receptors in the cell membrane, changing them from a confined to a freely
      diffusing state. By promoting NPFF-MOP receptor heteromerization, 1DMe could
      disrupt the domain organization of MOP receptors in the membrane, resulting in a
      reduction of opioid response.

PMID- 17224451
TI  - Changes in the balance between caldesmon regulated by p21-activated kinases and
      the Arp2/3 complex govern podosome formation.
AB  - Podosomes are dynamic cell adhesion structures that degrade the extracellular
      matrix, permitting extracellular matrix remodeling. Accumulating evidence
      suggests that actin and its associated proteins play a crucial role in podosome
      dynamics. Caldesmon is localized to the podosomes, and its expression is down
      regulated in transformed and cancer cells. Here we studied the regulatory mode of
      caldesmon in podosome formation in Rous sarcoma virus-transformed fibroblasts.
      Exogenous expression analyses revealed that caldesmon represses podosome
      formation triggered by the N-WASP-Arp2/3 pathway. Conversely, depletion of
      caldesmon by RNA interference induces numerous small-sized podosomes with high
      dynamics. Caldesmon competes with the Arp2/3 complex for actin binding and
      thereby inhibits podosome formation. p21-activated kinases (PAK)1 and 2 are also
      repressors of podosome formation via phosphorylation of caldesmon. Consequently,
      phosphorylation of caldesmon by PAK1/2 enhances this regulatory mode of
      caldesmon. Taken together, we conclude that in Rous sarcoma virus-transformed
      cells, changes in the balance between PAK1/2-regulated caldesmon and the Arp2/3
      complex govern the formation of podosomes.

PMID- 17224453
TI  - Oxidation and nitrosylation of cysteines proximal to the intermediate filament
      (IF)-binding site of plectin: effects on structure and vimentin binding and
      involvement in IF collapse.
AB  - As an intermediate filament (IF)-based cytolinker protein, plectin plays a key
      role in the maintenance of cellular cytoarchitecture and serves at the same time
      as a scaffolding platform for signaling cascades. Consisting of six structural
      repeats (R1-6) and harboring binding sites for different IF proteins and proteins
      involved in signaling, the plectin C-terminal domain is of strategic functional
      importance. Depending on the species, it contains at least 13 cysteines, 4 of
      which reside in the R5 domain. To investigate the structural and biological
      functions of R5 cysteines, we used cysteine-to-serine mutagenesis and
      spectroscopic, biochemical, and functional analyses. Urea-induced unfolding
      experiments indicated that wild-type R5 in the oxidized, disulfide bond-mediated
      conformation was more stable than its cysteine-free mutant derivative. The
      binding affinity of R5 for vimentin was significantly higher, however, when the
      protein was in the reduced, more relaxed conformation. Of the four R5 cysteines,
      one (Cys4) was particularly reactive as reflected by its ability to form
      disulfide bridges with R5 Cys1 and to serve as a target for nitrosylation in
      vitro. Using immortalized endothelial cell cultures from mice, we show that
      endogenous plectin is nitrosylated in vivo, and we found that NO donor-induced IF
      collapse proceeds dramatically faster in plectin-deficient compared with wild
      type cells. Our data suggest an antagonistic role of plectin in nitrosylation
      (oxidative stress)-mediated alterations of IF cytoarchitecture and a possible
      role of R5 Cys4 as a regulatory switch.

PMID- 17224452
TI  - Dynamic assembly of TRPC1-STIM1-Orai1 ternary complex is involved in store
      operated calcium influx. Evidence for similarities in store-operated and calcium
      release-activated calcium channel components.
AB  - Store-operated calcium entry (SOCE) is a ubiquitous mechanism that is mediated by
      distinct SOC channels, ranging from the highly selective calcium release
      activated Ca2+ (CRAC) channel in rat basophilic leukemia and other hematopoietic
      cells to relatively Ca2+-selective or non-selective SOC channels in other cells.
      Although the exact composition of these channels is not yet established, TRPC1
      contributes to SOC channels and regulation of physiological function of a variety
      of cell types. Recently, Orai1 and STIM1 have been suggested to be sufficient for
      generating CRAC channels. Here we show that Orai1 and STIM1 are also required for
      TRPC1-SOC channels. Knockdown of TRPC1, Orai1, or STIM1 attenuated, whereas
      overexpression of TRPC1, but not Orai1 or STIM1, induced an increase in SOC entry
      and I(SOC) in human salivary gland cells. All three proteins were co-localized in
      the plasma membrane region of cells, and thapsigargin increased co
      immunoprecipitation of TRPC1 with STIM1, and Orai1 in human salivary gland cells
      as well as dispersed mouse submandibular gland cells. In aggregate, the data
      presented here reveal that all three proteins are essential for generation of
      I(SOC) in these cells and that dynamic assembly of TRPC1-STIM1-Orai1 ternary
      complex is involved in activation of SOC channel in response to internal Ca2+
      store depletion. Thus, these data suggest a common molecular basis for SOC and
      CRAC channels.

PMID- 17224454
TI  - Tyrosine phosphorylation of missing in metastasis protein is implicated in
      platelet-derived growth factor-mediated cell shape changes.
AB  - Missing in metastasis gene, or MTSS1, encodes an intracellular protein that is
      implicated in actin cytoskeleton reorganization and often down-regulated in
      certain types of tumor cells. In response to platelet-derived growth factor
      (PDGF), green fluorescent protein (GFP)-tagged murine Mtss1 (Mtss1-GFP) underwent
      redistribution from the cytoplasm to dorsal membrane ruffles along with
      phosphorylation at tyrosine residues in a time-dependent manner. Tyrosine
      phosphorylation of Mtss1-GFP was also elevated in cells where an oncogenic Src
      was activated but severely impaired in Src knock-out cells or cells treated with
      Src kinase inhibitor PP2. Mutagenesis analysis has revealed that phosphorylation
      occurs at multiple sites, including tyrosine residues Tyr-397 and Tyr-398.
      Mutation at both Tyr-397 and Tyr-398 abolished the PDGF-mediated tyrosine
      phosphorylation. Furthermore, recombinant Mtss1 protein was phosphorylated by
      recombinant Src in a manner dependent on Tyr-397 and Tyr-398. Efficient tyrosine
      phosphorylation of Mtss1 in response to PDGF also involves a coiled-coil domain,
      which is essential for a proper distribution to the cell leading edge and dorsal
      ruffles. Interestingly, overexpression of wild type Mtss1-GFP promoted the PDGF
      induced dorsal ruffling, whereas overexpression of a mutant deficient in
      phosphorylation at Tyr-397 and Tyr-398 or a mutant with deletion of the coiled
      coil domain impaired the formation of dorsal ruffles. These data indicate that
      Mtss1 represents a novel signaling pathway from PDGF receptor to the actin
      cytoskeleton via Src-related kinases.

PMID- 17224455
TI  - Outcomes of dialysis initiated during the neonatal period for treatment of end
      stage renal disease: a North American Pediatric Renal Trials and Collaborative
      Studies special analysis.
AB  - OBJECTIVE: We sought to determine the outcomes of initiating long-term dialysis
      of neonates and children aged > 1 to 24 months with end-stage renal disease.
      PATIENTS AND METHODS: By querying the North American Pediatric Renal Trials and
      Collaborative Studies database, we obtained information on 193 neonates (< or = 1
      month of age) and 505 children (> 1-24 months of age) with a presumptive
      diagnosis of end-stage renal disease who initiated long-term dialysis. Dialysis
      characteristics and likelihood of hospitalization were compared using the chi2
      test, and duration of hospitalization was compared using the Wilcoxon 2-sample
      test. Product limit methods were implemented, and the log rank test was used to
      compare time-to-event analyses. Multivariate analyses were performed using Cox
      proportional hazards models. RESULTS: Neonates with end-stage renal disease were
      more likely to receive peritoneal dialysis versus hemodialysis than older
      children with end-stage renal disease. Moreover, neonates who initiated dialysis
      during the first month of life were just as likely to terminate dialysis as were
      the older children. Rates of renal transplantation were significantly lower in
      the neonates compared with the older children, but neonates were more likely to
      recover function of the native kidney. Although neonates were more often
      hospitalized, their overall risk of mortality was similar to that observed in
      older children. CONCLUSIONS: Neonates with a presumptive diagnosis of end-stage
      renal disease may initiate long-term dialysis during the first month of life with
      outcomes comparable to those of patients who initiate dialysis later in infancy.

PMID- 17224456
TI  - Provocation of neurocardiogenic syncope during head-up tilt testing in children:
      comparison between isoproterenol and nitroglycerin.
AB  - OBJECTIVE: Although nitroglycerin- and isoproterenol-augmented tilt tests are of
      equal value in the diagnosis of neurocardiogenic syncope in adults, no data exist
      in children. We compared the sensitivity and specificity of the 2 tests in a
      pediatric population. PATIENTS AND METHODS: We studied 85 patients (33 boys; mean
      age: 11.6 +/- 2.9 years). Of them, 56 had a diagnostic history of
      neurocardiogenic syncope, whereas 29 served as controls. After a negative passive
      phase, they were randomly assigned to either intravenous isoproterenol or
      sublingual nitroglycerin, and tilt was continued for 20 minutes. RESULTS:
      Sensitivity was 0.78 for the isoproterenol test and 0.79 for the nitroglycerin
      test, but specificity was significantly higher for isoproterenol test compared
      with nitroglycerin test. In patients with a positive test, the duration of the
      recovery period was significantly longer after nitroglycerin (8.4 +/- 2.7
      minutes) than after isoproterenol (5.1 +/- 1.6 minutes). CONCLUSIONS:
      Nitroglycerin- and isoproterenol-augmented tilt tests are associated with equal
      sensitivity in the diagnosis of neurocardiogenic syncope in children and
      adolescents. However, nitroglycerin results in more false-positive tests and
      produces more prolonged vasovagal symptoms. Our data do not support the routine
      use of nitroglycerin in the evaluation of syncope in this age group.

PMID- 17224457
TI  - Cognitive impairment after cerebral malaria in children: a prospective study.
AB  - OBJECTIVE: This study was conducted to assess prospectively the frequency of
      cognitive deficits in children with cerebral malaria. METHODS: Cognitive testing
      in the areas of working memory, attention, and learning was performed for Ugandan
      children 5 to 12 years of age with cerebral malaria (n = 44), children with
      uncomplicated malaria (n = 54), and healthy community children (n = 89) at
      admission and 3 and 6 months later. RESULTS: Six months after discharge, 21.4% of
      children with cerebral malaria had cognitive deficits, compared with 5.8% of
      community children. Deficits were seen in the areas of working memory (11.9% vs
      2.3%) and attention (16.7% vs 2.3%). Children with cerebral malaria had a 3.7
      fold increased risk of a cognitive deficit, compared with community children,
      after adjustment for age, gender, nutritional status, school level, and home
      environment. Among children with cerebral malaria, those with a cognitive deficit
      had more seizures before admission (mean: 4.1 vs 2.2) and a longer duration of
      coma (43.6 vs 30.5 hours), compared with those without a deficit. Children with
      uncomplicated malaria did not have an increased frequency of cognitive deficits.
      CONCLUSIONS: Cerebral malaria may be a major cause of cognitive impairment in
      children in sub-Saharan Africa. Cognitive deficits in children with cerebral
      malaria are more likely for those who have multiple seizures before effective
      treatment for cerebral malaria.

PMID- 17224458
TI  - Dry-rolled or steam-flaked grain-based diets and fecal shedding of Escherichia
      coli O157 in feedlot cattle.
AB  - Hindgut is a major colonization site for Escherichia coli O157 in cattle. In this
      study, diets were formulated to effect changes in hindgut fermentation to test
      our hypothesis that changes in the hindgut ecosystem could have an impact on
      fecal shedding of E. coli O157. Feedlot heifers (n = 347) were prescreened for
      the prevalence of E. coli O157 by fecal and rectoanal mucosal swab cultures. A
      subset of 40 heifers identified as being positive for fecal shedding of E. coli
      O157 was selected, housed in individual pens, and randomly allocated to 4 dietary
      treatments. Treatments were arranged as a 2 x 2 factorial, with factor 1
      consisting of grain type (sorghum or wheat) and factor 2 being method of grain
      processing (steam-flaking or dry-rolling). Four transition diets, each fed for 4
      d, were used to adapt the animals to final diets that contained 93% concentrate
      and 7% roughage. The grain fraction consisted of dry-rolled sorghum, steam-flaked
      sorghum, a mixture of dry-rolled wheat and steam-flaked corn, or a mixture of
      steam-flaked wheat and steam-flaked corn. Wheat diets contained 52% wheat and 31%
      steam-flaked corn (DM basis). Fecal and rectoanal mucosal swab samples were
      obtained 3 times a week to isolate (enrichment, immunomagenetic separation, and
      plating on selective medium) and identify (sorbitol negative, indole production,
      and agglutination test) E. coli O157. The data were analyzed as repeated measures
      of binomial response (positive or negative) on each sampling day. Method of
      processing (dry-rolled vs. steam-flaked), sampling day, and the grain type x day
      interaction were significant (P < 0.05), but not the method of processing x grain
      type interaction. The average prevalence of E. coli O157 from d 9 was greater (P
      < 0.001) in cattle fed steam-flaked grains (65%) compared with those fed dry
      rolled grains (30%). Average prevalence in cattle fed sorghum (51%) or wheat
      (43%) were similar (P > 0.10) on most sampling days. Results from this study
      indicate that feeding dry-rolled grains compared with steam-flaked grains reduced
      fecal shedding of E. coli O157. Possibly, dry-rolling allowed more substrate to
      reach the hindgut where it was fermented, thus making the hindgut inhospitable to
      the survival of E. coli O157. Dietary intervention to influence hindgut
      fermentation offers a simple and practical mitigation strategy to reduce the
      prevalence of E. coli O157 in feedlot cattle.

PMID- 17224459
TI  - Performance of gestating sows in bedded hoop barns and confinement stalls.
AB  - The effects of gestation housing systems on sow and litter performance were
      evaluated for 2.5 yr in southwest Iowa. Gestation housing system treatments were
      as follows: 1) individual gestation stalls in a mechanically ventilated
      confinement building with a partially slatted floor and a manure flush system and
      2) group pens with individual feed stalls in deep-bedded, naturally ventilated
      hoop barns. In all, 957 litters from 353 sows were evaluated. Number of pigs born
      alive per litter differed for the 2 housing treatments (P = 0.002). Sows gestated
      in hoop barns gave birth to more live pigs per litter (10.0 +/- 0.2 pigs) than
      sows gestated in stalls (9.3 +/- 0.2 pigs). Preweaning mortality was not
      different for the 2 housing treatments (P = 0.70). Cross-fostering was done to
      equalize litter size within 24 h of birth, which resulted in an equal number of
      weaned pigs per sow (P = 0.50) regardless of gestation housing treatment. The
      weaning-to-breeding interval was different (P = 0.01), with sows kept in stalls
      (4.3 +/- 0.6 d) returning to estrus sooner than sows gestated in hoop barns (6.0
      +/- 0.6 d). These results indicate that gestating sows can be housed as groups in
      deep-bedded hoop barns equipped with individual feeding stalls and will perform
      comparably to gestating sows housed in confinement systems with individual
      gestation stalls.

PMID- 17224461
TI  - Adiposity of calf- and yearling-fed Brangus steers raised to constant-age and
      constant-body weight endpoints.
AB  - We tested the hypothesis that fatty acid biosynthesis and adipocyte diameter and
      volume would be greater in s.c. and i.m. adipose tissues of calf-fed steers than
      in yearling-fed steers at a constant BW, due to the greater time on feed for the
      calf-fed steers. Conversely, we predicted that the capacity for s.c. and i.m.
      preadipocytes to divide, as estimated by 3H-thymidine incorporation into DNA,
      would be greater in the less mature adipose tissues of calf-fed steers and in
      yearling-fed steers at 16 mo of age than in yearling-fed steers fed to 18 mo of
      age. Brangus steers were fed a corn-based finishing diet as calves (calf-fed; n =
      9) or yearlings (n = 4) to 16 mo of age (CA yearling-fed); another group of
      yearlings (n = 5) was fed to a constant-BW end point of 530 kg (CW yearling-fed).
      Both groups of yearling-fed steers had free access to native pasture until 12 mo
      of age. At slaughter, the fifth to eighth thoracic rib section of the LM was
      removed, and fresh s.c. and i.m. adipose tissues were removed for in vitro
      incubations. There were no differences in the number of s.c. adipocytes/g or mean
      peak volumes of adipocytes across production groups (P > or = 0.14). However,
      s.c. adipose tissue of CA yearling-fed steers contained greater proportions of
      smaller adipocytes (<1,500 pL) than calffed or CW yearling-fed steers, and
      similar results were observed for i.m. adipose tissue. Acetate incorporation into
      total lipids was greater (P = 0.02) in s.c. adipose tissue of CA yearling-fed
      steers than in calf-fed or CW yearling-fed steers, and tended to be different (P
      = 0.10) across production groups in i.m. adipose tissue. The production system x
      cell fraction interaction was significant (P = 0.03) for s.c. adipose tissue DNA
      synthesis, which was greatest in adipocytes from CA yearling-fed steers, whereas
      there were no differences across production system in stromal vascular (SV) DNA
      synthesis. For i.m. adipose tissue, DNA synthesis was greatest in adipocytes and
      SV cells from CA yearling-fed calves, and was greater in SV cells than in
      adipocytes (both P = 0.01). Therefore, stage of adipose tissue development more
      strongly influenced fatty acid synthesis, adipocyte volume, and DNA synthesis
      than age at sampling, final BW, or time on the finishing diet.

PMID- 17224460
TI  - Maternal undernutrition during early to mid-gestation in the ewe results in
      altered growth, adiposity, and glucose tolerance in male offspring.
AB  - This study utilized maternal undernutrition from early to midgestation in the ewe
      to determine the impact(s) of intrauterine growth restriction on postpartum
      growth of male offspring and the potential mechanisms involved. Multiparous ewes
      were fed 50% (nutrient-restricted) or 100% (control-fed) of their nutrient
      requirements (NRC, 1985) between d 28 and 78 of gestation, and then all ewes were
      fed 100% of the NRC requirements from d 79 through lambing. Male lambs born to
      nutrient-restricted (n = 9) and control-fed (n = 9) ewes exhibited similar BW
      (5.8 vs. 6.0 +/- 0.3 kg) and crown-rump lengths (53.8 vs. 55.4 +/- 1.0 cm) at
      birth. At 63 and 250 d of postnatal age, wether lambs were subjected to a glucose
      tolerance test, in which a bolus of glucose was administered i.v. to evaluate
      changes in glucose and insulin concentrations. After i.v. glucose administration
      at 63 d of age, lambs from nutrient-restricted ewes exhibited a greater area
      under the curve for glucose (AUCg; 6,281 vs. 5,242 +/- 429; P < 0.05) and insulin
      (AUCi; 21.0 vs. 8.6 +/- 1.9; P < 0.001) than lambs from control-fed ewes. After
      glucose administration at 250 d of age, lambs from nutrient-restricted ewes had
      greater AUCg (7,147 vs. 5,823 +/- 361; P < 0.01) but a lower AUCi (6.4 vs. 10.2
      +/- 1.9; P = 0.05) than lambs from control-fed ewes. Lambs from nutrient
      restricted ewes were heavier (26.6 vs. 21.8 +/- 2.3 kg; P < 0.05) and had more
      backfat (0.30 vs. 0.21 +/- 0.03 cm, P < 0.05) by 4 mo of age than the lambs from
      control-fed ewes. At slaughter at 280 d of age, lambs from nutrient-restricted
      ewes remained heavier than lambs from control-fed ewes, had greater (P < 0.05)
      amounts of kidney and pelvic-area adipose tissue, and tended (P < 0.10) to have
      reduced LM and semitendinosus muscle weights as a percentage of HCW. These data
      demonstrate that a bout of maternal undernutrition during early to midgestation
      in sheep increased BW and fat deposition during adolescence and dysregulated
      glucose uptake in the absence of any change in birth weight.

PMID- 17224462
TI  - Patterns of late embryonic and fetal mortality and association with several
      factors in sheep.
AB  - Embryonic and fetal mortality reduce lambing rates and litter sizes, thus
      contributing to economic losses in the sheep industry. In the current study, the
      timing of late embryonic and fetal loss in ewes and the factors with which these
      losses were associated were examined. Ewes lambing and lambs born were compared
      with pregnancy diagnosis and counts of embryos by ultrasonography near d 25, 45,
      65, or 85 of gestation. Approximately 19.9% of the ewes experienced late
      embryonic loss, fetal loss, or both; and 21.2% of the embryos or fetuses were
      lost from d 25 to term. Potential offspring were lost throughout gestation; 3.7%
      of embryos from d 25 to 45, 4.3% of fetuses from d 45 to 65, 3.3% from d 65 to
      85, and 11.5% from d 85 to parturition; thus, approximately 3 to 4% of the
      potential offspring were lost for each 20-d period of pregnancy beyond d 25. A
      greater proportion of ewes lost one (36.7%) rather than all (20.5% single; 3.8%
      multiple) embryos or fetuses. The patterns of loss were similar in ewes mated
      during the anestrous season and the transitional period and did not vary with
      service period within breeding season or method of synchronization of estrus.
      Late embryonic or fetal losses were not related to the temperature-humidity
      index. Maternal serum collected near d 25, 45, 65, or 85 of gestation was assayed
      for concentrations of progesterone, estradiol-17beta , and vascular endothelial
      growth factor (VEGF). The proportions of embryos or fetuses lost were associated
      with breed type (P < 0.05), as were concentrations of progesterone (P < 0.01),
      estradiol (P < 0.05), and VEGF (P < 0.01). The relationships of loss or retention
      of pregnancy to hormonal variables at the 4 stages studied were limited. Complete
      and partial losses increased rapidly as maternal progesterone at d 25 decreased
      below 2 ng/mL (P < 0.05). Survival of fetuses within a litter from d 25 to 65 was
      greater for ewes with medium concentrations of VEGF near d 25 and from d 65 to
      parturition was greater for ewes with high concentrations of VEGF near d 45 (P <
      0.05). In summary, late embryonic or fetal losses occurred from d 25 throughout
      gestation and varied with breed type and with concentrations of progesterone in
      maternal serum on d 25.

PMID- 17224464
TI  - Corn oil supplementation to steers grazing endophyte-free tall fescue. I. Effects
      on in vivo digestibility, performance, and carcass traits.
AB  - Eighteen Angus steers (438 +/- 4 kg of BW) were supplemented with varying levels
      of corn oil (0 g/kg of BW, none; 0.75 g/kg of BW, MED; or 1.5 g/kg of BW, HI) on
      rotationally stocked, endophyte-free tall fescue to determine the effect of
      supplemental oil level on in vivo digestibility, intake, performance, and carcass
      traits. Pelleted cottonseed hulls were used as a carrier for the oil supplements,
      and all supplements were offered to steers using Calan gate feeders for
      individual intake determination. On d 49, each steer was dosed with a controlled
      release capsule containing chromium sesquioxide, and fecal samples were obtained
      12 d later over a 7-d period to estimate fecal output that, with forage,
      supplement, and fecal indigestible NDF concentration, was used to estimate DMI
      and in vivo total diet digestibility. Steers were slaughtered at the end of the
      116-d grazing period, and carcass data were collected at 24 h postmortem. Total
      fatty acid intake linearly increased with corn oil supplementation, and forage
      DMI, total DMI, and total DE intake were linearly decreased (P < 0.01). The
      decrease in total DMI was reflected in forage substitution rates greater (P < or
      = 0.01) than 1, with a trend (P = 0.09) for a greater substitution rate in HI
      than in MED. In vivo DM, OM, and NDF digestibility were linearly decreased (P <
      0.01) by corn oil supplementation. Average daily gain and final BW tended (P =
      0.09) to increase linearly in response to oil level. Oil conversion (0.36 kg of
      BW gain/kg of corn oil) was greater (P < or = 0.05) than zero and did not differ
      (P = 0.15) between MED and HI. Dressing percent (P = 0.09), carcass weight (P =
      0.01), and carcass backfat thickness (P = 0.01) increased linearly with oil
      supplementation. No treatment effect was observed for carcass LM area, KPH
      percentage, marbling score, or yield grade (P > 0.10). Oil supplementation to
      grazing steers linearly reduced forage DMI intake; however, animal performance
      was maintained and tended to be greater for oil-supplemented cattle. Oil
      supplementation increased carcass fat thickness and weight without altering other
      carcass quality parameters.

PMID- 17224463
TI  - Digestibility of energy and phosphorus in ten samples of distillers dried grains
      with solubles fed to growing pigs.
AB  - An experiment was conducted to measure DE and ME and the apparent total tract
      digestibility (ATTD) of energy, N, and P in distillers dried grains with solubles
      (DDGS) fed to growing pigs. Ten sources of DDGS were obtained from ethanol plants
      in South Dakota and Minnesota, and 11 diets were formulated. One diet was based
      on corn (96.8%), limestone, salt, vitamins, and microminerals. Ten additional
      diets were formulated by mixing the corn diet and each of the 10 sources of DDGS
      in a 1:1 ratio. Eleven growing pigs (initial BW of 29.3 +/- 0.42 kg) were
      allotted to an 11 x 11 Latin square design, with 11 periods and 11 pigs. Each of
      the 11 diets was fed to each pig during 1 period. Pigs were placed in metabolism
      cages that allowed for the total, but separate, collection of feces and urine.
      Samples were analyzed for GE, N, and P and energy and N balances, and the ATTD of
      GE, N, and P were calculated for each diet. By subtracting the contribution from
      the corn diet to the DDGS-containing diets, the energy and N balances and the
      ATTD for GE, N, and P for each source of DDGS were calculated. Results of the
      experiment showed that the DE and ME differed (P < 0.001) among the 10 sources of
      DDGS (3,947 to 4,593 kcal of DE/kg of DM and 3,674 to 4,336 kcal of ME/kg of DM).
      The average DE and ME in DDGS were 4,140 and 3,897 kcal/kg of DM, respectively.
      These values were not different from the DE and ME in corn (4,088 and 3,989
      kcal/kg of DM, respectively). Based on the analyzed GE and nutrient composition
      of DDGS and the calculated values for DE and ME, prediction equations for DE and
      ME were developed. These equations showed that DE and ME in DDGS may be predicted
      from the concentration of ash, ether extract, ADF, and GE. The retention of N
      from DDGS was greater (P < 0.001) than from corn, but when calculated on a
      percentage basis, the N retention did not differ between DDGS and corn. The ATTD
      of P in DDGS was 59.1% on average for the 10 samples. This value was greater (P <
      0.001) than the ATTD of P in corn (19.3%). It is concluded that the DE and ME in
      DDGS is not different from the DE and ME in corn. However, if DDGS is included in
      diets fed to growing swine, a greater portion of the organic P will be digested
      and absorbed, thus reducing the need for adding inorganic P to the diets.

PMID- 17224465
TI  - Cattle performance and production when grazing Bermudagrass at two forage mass
      levels in the southern Piedmont.
AB  - Performance and production of growing cattle (Bos taurus) on Coastal Bermudagrass
      [Cynodon dactylon (L.) Pers.] pasture are affected by forage allowance, but
      possible interactions with fertilizer nutrient source (i.e., inorganic vs.
      organic) and time have not been well described. We evaluated the effects of 3
      nutrient sources with equivalent N rates: 1) inorganic, 2) crimson clover
      (Trifolium incarnatum L.) cover crop plus inorganic, and 3) chicken (Gallus
      gallus) broiler litter, factorially arranged with 2 residual forage mass levels
      [grazing to maintain high (4,528 +/- 1,803 kg/ha) and low (2,538 +/- 1,264 kg/ha)
      forage mass], on cattle stocking density, ADG, and BW gain during 5 consecutive
      summer grazing seasons. Across grazing seasons, residual forage mass and nutrient
      source both affected response variables, but interactions between these variables
      were rarely significant (P < or = 0.10). Across grazing seasons and nutrient
      sources, increasing grazing pressure to maintain a lower forage mass reduced ADG
      (0.67 vs. 0.88 kg/d; P < 0.001) but increased BW gain/ha (726 vs. 578 kg/ha; P <
      0.001) due to greater stocking density (8.7 vs. 5.8 steers/ha, P < 0.001; mean BW
      of growing Angus steers of 212 kg). Inorganic fertilization led to greater
      stocking density than other nutrient sources (8.2 vs. 6.8 steers/ha, P < 0.001)
      because of greater forage production. Stocking density to achieve the 2 targeted
      forage mass levels was widely different during the initial grazing seasons of the
      study but nearly similar at the end of 5 yr. Cattle performance tended to decline
      with time during each grazing season under both residual forage mass levels,
      perhaps as a result of declining forage quality, because performance was
      positively associated with grazing season precipitation under high forage mass.
      Steer BW gain/ha was greater (P < 0.05) with lower forage mass early in the
      grazing season of all years but not necessarily later in the grazing season.
      Steer BW gain/ha was also greater (P < 0.05) with a lower forage mass during the
      early years of the study but was similar during the later years of the study.
      Significant variations in cattle performance and production with time confirmed
      the short-term seasonal effects but suggested that the long-term effects may also
      be of importance in maintaining productivity and environmental quality of grazed
      pastures.

PMID- 17224466
TI  - Heart rate measurements as an index of energy expenditure and energy balance in
      ruminants: a review.
AB  - A major part of the ME consumed by ruminants (MEI) is dissipated as heat. This
      fraction, called heat production or energy expenditure (EE), is assayed largely
      by measuring O2 consumption (VO2). Conventional measurement of EE in controlled
      conditions in chambers does not reflect the complexity of natural, environmental,
      and social conditions of free-ranging animals. In mammals, most of the measured
      VO2 is transferred to the tissues through the heart; therefore, regression of
      heart rate (HR) against VO2 can be used to estimate the EE of free-ranging
      animals. The present article reviews the current knowledge on the use of HR for
      estimating EE. Energy expenditure can be determined from HR measurements,
      recorded daily over the course of several days, multiplied by the VO2 per beat.
      When an animal does not perform significant exercise, a constant value of VO2 per
      beat [O2 pulse (O2P)] measured over a short period (10 to 15 min) is used; during
      exercise, O2P increases, and the regression equation of VO2 against HR is used.
      Under extreme heat load, HR increases to improve heat dissipation, and O2P
      decreases; therefore, the effect of heat load on O2P needs to be taken into
      account. Cold stress that doubles heat production does not affect O2P. Heart rate
      and EE are highly correlated with MEI, but there is significant individual
      variation in the relationship; therefore, the daily change in the HR of
      individual animals can be used as an indicator of changes in the individual
      energy status of a ruminant, and the average HR of the group can serve in the
      estimation of the energy status of the group. When O2P is measured, the average
      group EE is an indication of the energy balance of the whole group. Because the
      MEI of nondraft animals is the sum of EE and retained energy (RE), the MEI of
      free-ranging ruminants can be determined by measurement of EE by the HR method
      and adding the RE. Similarly, the RE can be determined without slaughtering the
      animals from measurements of EE and MEI. Soon when devices for automatic HR
      monitoring of domestic ruminants become available at a reasonable price,
      continuous monitoring of HR might provide producers with a sensitive tool for
      identifying changes in the energy status of their animals. This will also
      significantly help to shorten the time needed to identify health problems of
      individual animals.

PMID- 17224467
TI  - Genetic evaluation of beef carcass data using different endpoint adjustments.
AB  - Carcass data from 6,795 Simmental-sired animals born from 1992 to 2001 were used
      to determine whether adjustment to a constant age, back-fat, HCW, or marbling
      score would result in differences in heritability of the carcass traits and,
      correspondingly, if EPD calculated using those variance components and
      adjustments would result in sire reranking. The endpoints were age (EPA), backfat
      (EPF), HCW (EPC), or marbling (EPM). The traits analyzed were 12th-rib backfat
      (FAT), HCW, marbling (MRB), LM area (LMA), and percentage retail cuts (PRC). The
      data were analyzed using an animal model, where contemporary group was included
      as a fixed effect and was composed of slaughter date, sex, and herd. Random
      effects included in the model were direct genetic and residual. Estimates of
      heritability ranged from 0.12 to 0.14, 0.32 to 0.34, and 0.26 to 0.27 for FAT,
      HCW, and LMA, respectively, for the corresponding endpoints. Heritability for MRB
      was estimated to be 0.27 at all endpoints. For PRC, estimates of heritability
      were more variable, with estimates of 0.23 +/- 0.05, 0.32 +/- 0.05, 0.21 +/-
      0.05, and 0.20 +/- 0.04 for EPA, EPF, EPC, and EPM, respectively. However,
      because the EPF and EPC adjustments adjust for a component trait of PRC (FAT and
      HCW, respectively), they may be altering the trait to one different from PRC.
      Spearman rank correlations between EPD within a trait using EPA compared with the
      other endpoints were >0.90 (P < 0.01) for FAT, HCW, MRB, and LMA. For PRC,
      Spearman rank correlations with EPA EPD were 0.73 (P < 0.01), 0.93 (P < 0.01),
      and 0.95 (P < 0.01) for EPF, EPC, and EPM, respectively. For most traits and
      endpoints, there was little reranking among sires when alternative endpoints were
      used. However, adjusting PRC to EPF appears to result in a greater heritability
      and substantial re-ranking of sires, potentially due to the adjustment changing
      the trait to one other than PRC.

PMID- 17224468
TI  - Genome-wide linkage mapping for valve calcification susceptibility loci in
      hypertensive sibships: the Hypertension Genetic Epidemiology Network Study.
AB  - It remains unclear whether genetic factors contribute to the susceptibility to
      valve calcification. Accordingly, echocardiograms and genotyping were performed
      in 1871 hypertensive siblings who participated in the Hypertension Genetic
      Epidemiology Network Study. Genome-wide affected sibpair nonparametric linkage
      analysis was conducted using the allele-sharing method implemented in the Merlin
      computer program. A total of 1014 sibships from 858 families were evaluated for
      aortic valve sclerosis or mitral annular calcification. Of these, 78 sibships
      from 68 families contained > or =2 affected siblings with > or =1 type of valve
      calcification (142 affected siblings). All 3 of the traits showed a modest degree
      of familial aggregation, with sibling recurrence risk (SD) and sibling recurrence
      risk ratio (95% CI) being 0.25 (0.035) and 2.31 (1.72 to 3.11) for aortic valve
      sclerosis, 0.25 (0.035) and 1.78 (1.36 to 2.33) for mitral annular calcification,
      and 0.31 (0.030) and 1.52 (1.24 to 1.85) for aortic valve sclerosis and mitral
      annular calcification, respectively. Affected sibpair linkage analysis revealed
      the highest logarithm of odds score (3.14) in chromosome 16 at 105.6 cM for
      aortic valve sclerosis. Other chromosomal regions with logarithm of odds score >
      or =1.9 were found in chromosomes 19 (2.88), 16 (2.63), 1 (2.12), and 2 (2.03)
      for aortic valve sclerosis and chromosome 13 (2.12) for any valve calcification.
      There was no logarithm of odds score > or =1.9 for mitral annular calcification.
      Our study shows strong linkage of aortic valve sclerosis to chromosome 16q22.1
      q22.3 and suggestive linkage to chromosome 19p13.11-p11 and identifies several
      other promising genomic regions that may contain specific susceptibility loci for
      valve calcification.

PMID- 17224469
TI  - Exercise training prevents arterial baroreflex dysfunction in rats treated with
      central angiotensin II.
AB  - Angiotensin II (Ang II)-induced arterial baroreflex dysfunction is associated
      with superoxide generation in the brain. Exercise training (EX) improves
      baroreflex function and decreases oxidative stress in cardiovascular diseases
      linked to elevated central Ang II. The aim of this study was to determine whether
      previous EX prevents baroreflex impairment caused by central administration of
      exogenous Ang II via an Ang II-superoxide mechanism. Four groups of rats were
      used: non-EX artificial cerebrospinal fluid infused, non-EX Ang II infused, EX
      artificial cerebrospinal fluid infused, and EX Ang II infused. Rats were
      treadmill trained for 3 to 4 weeks and subjected to intracerebroventricular
      infusion of Ang II over the last 3 days of EX. Twenty-four hours after the end of
      EX, the arterial baroreflex was assessed in anesthetized rats. Compared with non
      EX artificial cerebrospinal fluid-infused rats, Ang II significantly decreased
      baroreflex sensitivity (maximum gain: 3.0+/-0.2% of maximum per millimeter of
      mercury versus 1.6+/-0.1% of maximum per millimeter of mercury; P<0.01), which
      was abolished by acute intracerebroventricular infusion of the Ang II type 1
      receptor antagonist losartan and the reduced nicotinamide-adenine dinucleotide
      phosphate oxidase inhibitor apocynin. EX prevented the decrease in baroreflex
      sensitivity and downregulated Ang II type 1 receptor and NADPH oxidase subunit
      protein expression in the paraventricular nucleus of Ang II-infused rats.
      Finally, EX decreased superoxide production in the paraventricular nucleus of Ang
      II-infused rats. These results indicate that EX improves arterial baroreflex
      function in conditions of high brain Ang II, which is mediated by the central Ang
      II type 1 receptor and associated with a reduction in central oxidative stress.

PMID- 17224470
TI  - p38 mitogen-activated protein kinase inhibition ameliorates angiotensin II
      induced target organ damage.
AB  - We investigated whether or not p38 mitogen-activated protein kinase inhibition
      ameliorates angiotensin II-induced target organ damage. We used double transgenic
      rats harboring both human renin and angiotensinogen genes (dTGRs). dTGR, with or
      without p38 inhibitor (BIRB796; 30 mg/kg per day in the diet), and nontransgenic
      Sprague-Dawley rats were studied in 2 protocols. In protocol 1 (week 7), systolic
      blood pressure of untreated dTGRs was 204+/-4 mm Hg, but partially reduced after
      BIRB796 treatment (166+/-7 mm Hg), whereas Sprague-Dawley rats were normotensive.
      The cardiac hypertrophy index was unchanged in untreated and BIRB796-treated
      dTGRs. The beta-myosin heavy chain expression of BIRB796-treated hearts was
      significantly lower in BIRB796 compared with dTGRs, indicating a delayed switch
      to the fetal isoform. BIRB796 treatment significantly reduced cardiac fibrosis,
      connective tissue growth factor, tumor necrosis factor-alpha, interleukin-6, and
      macrophage infiltration. Albuminuria was not reduced in BIRB796-treated dTGRs.
      Tubular and glomerular damage with tumor necrosis factor-alpha expression was
      unaltered, although serum creatinine and cystatin C were normalized. Renal
      macrophage infiltration, fibrosis, and vessel damage were reduced. In protocol 2
      (week 8), we focused on mortality and arrhythmogenic electrical remodeling.
      Mortality of untreated dTGRs was 100% but was reduced to 10% in the BIRB796
      group. Cardiac magnetic field mapping showed prolongation of depolarization and
      repolarization in untreated dTGRs compared with Sprague-Dawley rats with a
      partial reduction by BIRB796. Programmed electrical stimulation elicited
      ventricular tachycardias in 81% of untreated dTGRs but only in 48% of BIRB796
      treated dTGRs. In conclusion, BIRB796 improved survival, target organ damage, and
      arrhythmogenic potential in angiotensin II-induced target organ damage.

PMID- 17224471
TI  - Sympathetic hyperactivity in hypertensive chronic kidney disease patients is
      reduced during standard treatment.
AB  - Standard treatment in chronic kidney disease (CKD) patients includes an
      angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. CKD
      is often characterized by sympathetic hyperactivity. This study investigates the
      prevalence of sympathetic hyperactivity (quantified by assessment of muscle
      sympathetic nerve activity [MSNA]) in a sizable group of patients with CKD and
      assessed whether chronic angiotensin-converting enzyme inhibitor or angiotensin
      II receptor blocker normalizes increased MSNA. In 74 CKD patients (creatinine
      clearance 54+/-31 mL/min), MSNA, blood pressure, and plasma renin activity were
      measured in the absence of antihypertensive drugs except for diuretics. In a
      subgroup of 31 patients, another set of measurements was obtained after > or =6
      weeks of enalapril (10 mg PO), losartan (100 mg PO), or eprosartan (600 mg PO).
      Patients as compared with control subjects (n=82) had higher mean arterial
      pressure (113+/-13 versus 89+/-7 mm Hg), MSNA (31+/-13 versus 19+/-7 bursts per
      minute), and log plasma renin activity (2.67+/-036 versus 2.40+/-0.32 fmol/L per
      second; all P<0.001). During angiotensin-converting enzyme inhibitor or
      angiotensin II receptor blocker therapy (n=31), mean arterial pressure (115+/-11
      to 100+/-9 mm Hg) and MSNA (33+/-11 to 25+/-9 bursts per minute) decreased (both
      P<0.01) but were still higher than in control subjects (both P<0.01). Multiple
      regression analysis identified age and plasma renin activity as predictive for
      MSNA. In conclusion, sympathetic hyperactivity occurs in a substantial proportion
      of hypertensive CKD patients. Angiotensin-converting enzyme inhibitor or
      angiotensin II receptor blocker treatment reduces but does not normalize MSNA.

PMID- 17224472
TI  - Left ventricular mass, blood pressure, and lowered cognitive performance in the
      Framingham offspring.
AB  - The purpose of this study was to determine whether echocardiographic left
      ventricular mass is related to cognitive performance beyond casual blood pressure
      adjusting for the influence of other vascular risk factors. We used multivariable
      regression analyses to relate left ventricular mass assessed at a routine
      examination (1995-1998) to measures of cognitive ability obtained routinely (1998
      2001) in 1673 Framingham Offspring Study participants (56% women; mean age: 57
      years) free from stroke, transient ischemic attack, and dementia. We adjusted for
      the following covariates hierarchically: (1) age, education, sex, body weight,
      height, interval between left ventricular mass measurement and neuropsychological
      testing (basic model); (2) basic model+blood pressure+treatment for hypertension;
      and (3) basic model+blood pressure+treatment for hypertension+vascular risk
      factors and prevalent cardiovascular disease. For the basic model, left
      ventricular mass was inversely associated with abstract reasoning (similarities),
      visual-spatial memory and organization, and verbal memory. For the basic
      model+blood pressure+treatment for hypertension, left ventricular mass was
      inversely associated with similarities and visual-spatial memory and
      organization. For the basic+blood pressure+treatment for hypertension+risk
      factors+cardiovascular disease model, no significant associations were observed.
      Echocardiographic left ventricular mass is associated with cognitive performance
      beyond casual and time-averaged systolic blood pressure, but this association is
      attenuated and rendered nonsignificant with additional adjustment for
      cardiovascular risk factors and cardiovascular disease, thus suggesting that
      these variables play an important role in mediating the association between left
      ventricular mass and cognition.

PMID- 17224473
TI  - Ala92 type 2 deiodinase allele increases risk for the development of
      hypertension.
AB  - Accumulating evidence suggests that genes of the hypothalamic-pituitary-thyroid
      pathway influence susceptibility to hypertension. Type 2 iodothyronine deiodinase
      is responsible for the conversion of thyroxine to tri-iodothyronine for use in
      peripheral tissues. The present study evaluated whether a type 2 iodothyronine
      deiodinase nonsynonymous polymorphism, threonine 92 to alanine (Thr92Ala), is a
      determinant of hypertension susceptibility. A total of 372 euthyroid subjects
      were genotyped for Thr92Ala polymorphism using the Sequenom MassARRAY platform.
      Associations with hypertension and hypertension-related intermediate phenotypes
      were performed with generalized estimating equations. Type 2 iodothyronine
      deiodinase Thr92Ala allele frequencies differed significantly between
      hypertensive and normotensive subjects, with an excess of Ala92 carriers in
      hypertensive compared with normotensive subjects (64.8% versus 47.1%; P=0.011).
      Adjusted for age, gender and race, the estimated odds ratio for hypertension in
      Ala92 allele carriers compared with Thr92 homozygotes was 2.11 (95% CI: 1.15 to
      3.89). Among euthyroid adults, the common Ala92 allele of the type 2
      iodothyronine deiodinase increases risk for the development of hypertension.
      These data support an important role for genetic variation in the hypothalamic
      pituitary-thyroid pathway in influencing susceptibility to hypertension.

PMID- 17224474
TI  - Endocrine role of the renin-angiotensin system in human adipose tissue and
      muscle: effect of beta-adrenergic stimulation.
AB  - The renin-angiotensin system has been implicated in obesity-related hypertension
      and insulin resistance. We examined whether locally produced components of the
      renin-angiotensin system in adipose tissue and skeletal muscle play an endocrine
      role in vivo in humans. Furthermore, the effects of beta-adrenergic stimulation
      on plasma concentrations and tissue release of renin-angiotensin system
      components were investigated. Systemic renin-angiotensin system components and
      arteriovenous differences of angiotensin II (Ang II) and angiotensinogen (AGT)
      across abdominal subcutaneous adipose tissue and skeletal muscle were assessed in
      combination with measurements of tissue blood flow before and during systemic
      beta-adrenergic stimulation in 13 lean and 10 obese subjects. Basal plasma Ang II
      and AGT concentrations were not significantly different between lean and obese
      subjects. Ang II concentrations were increased in obese compared with lean
      subjects during beta-adrenergic stimulation (12.6+/-1.5 versus 8.1+/-1.0 pmol/L;
      P=0.04), whereas AGT concentrations remained unchanged. Plasma renin activity
      increased to a similar extent in lean and obese subjects during beta-adrenergic
      stimulation (both P<0.01). No net Ang II release across adipose tissue and
      skeletal muscle could be detected in both groups of subjects. However, AGT was
      released from adipose tissue and muscle during beta-adrenergic stimulation in
      obese subjects (both P<0.05). In conclusion, locally produced Ang II in adipose
      tissue and skeletal muscle exerts no endocrine role in lean and obese subjects.
      In contrast, AGT is released from adipose tissue and muscle in obese subjects
      during beta-adrenergic stimulation, which may contribute to the increased plasma
      Ang II concentrations during beta-adrenergic stimulation in obese subjects.

PMID- 17224475
TI  - Kinin infusion prevents renal inflammation, apoptosis, and fibrosis via
      inhibition of oxidative stress and mitogen-activated protein kinase activity.
AB  - The progression of renal disease displays several characteristics, including
      proteinuria, apoptosis, inflammation, and fibrosis. In this study, we
      investigated the effect of long-term infusion of kinin in protection against salt
      induced renal damage in Dahl salt-sensitive rats. Dahl salt-sensitive rats were
      fed a high-salt diet for 2 weeks and were then infused with bradykinin (500 ng/h)
      via subcutaneously implanted minipumps for 3 weeks. Kinin infusion attenuated
      salt-induced impaired renal function as evidenced by reduced proteinuria, serum
      creatinine, and blood urea nitrogen levels without apparent effect on blood
      pressure. Morphological analysis indicated that kinin administration reduced salt
      induced glomerular sclerosis, tubular dilatation, luminal protein cast formation,
      and interlobular arterial thickness. Kinin also significantly lowered collagen I,
      III, and IV deposition and their mRNA levels. Moreover, kinin reduced
      interstitial monocyte/macrophage accumulation, as well as tubular cell apoptosis
      and caspase-3 activity. Protection of renal injury by kinin was associated with
      increased renal NO levels and reduced nicotinamide adenine
      dinucleotide/nicotinamide adenine dinucleotide phosphate oxidase activities and
      superoxide generation. Suppression of oxidative stress by kinin was accompanied
      by reduced transforming growth factor-beta1 protein and mRNA levels, as well as
      decreased phosphorylation of mitogen-activated protein kinases. This is the first
      study to demonstrate that kinin infusion can directly protect against salt
      induced renal injury without blood pressure reduction by inhibiting apoptosis,
      inflammation, and fibrosis via suppression of oxidative stress, transforming
      growth factor-beta1 expression, and mitogen-activated protein kinase activation.

PMID- 17224476
TI  - Loss-of-function mutations in the cardiac calcium channel underlie a new clinical
      entity characterized by ST-segment elevation, short QT intervals, and sudden
      cardiac death.
AB  - BACKGROUND: Cardiac ion channelopathies are responsible for an ever-increasing
      number and diversity of familial cardiac arrhythmia syndromes. We describe a new
      clinical entity that consists of an ST-segment elevation in the right precordial
      ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac
      death. METHODS AND RESULTS: Eighty-two consecutive probands with Brugada syndrome
      were screened for ion channel gene mutations with direct sequencing. Site
      directed mutagenesis was performed, and CHO-K1 cells were cotransfected with
      cDNAs encoding wild-type or mutant CACNB2b (Ca(v beta2b)), CACNA2D1 (Ca(v
      alpha2delta1)), and CACNA1C tagged with enhanced yellow fluorescent protein
      (Ca(v)1.2). Whole-cell patch-clamp studies were performed after 48 to 72 hours.
      Three probands displaying ST-segment elevation and corrected QT intervals < or =
      360 ms had mutations in genes encoding the cardiac L-type calcium channel.
      Corrected QT ranged from 330 to 370 ms among probands and clinically affected
      family members. Rate adaptation of QT interval was reduced. Quinidine normalized
      the QT interval and prevented stimulation-induced ventricular tachycardia.
      Genetic and heterologous expression studies revealed loss-of-function missense
      mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the alpha1- and
      beta2b-subunits of the L-type calcium channel. Confocal microscopy revealed a
      defect in trafficking of A39V Ca(v)1.2 channels but normal trafficking of
      channels containing G490R Ca(v)1.2 or S481L Ca(v beta2b)-subunits. CONCLUSIONS:
      This is the first report of loss-of-function mutations in genes encoding the
      cardiac L-type calcium channel to be associated with a familial sudden cardiac
      death syndrome in which a Brugada syndrome phenotype is combined with shorter
      than-normal QT intervals.

PMID- 17224477
TI  - Model-dependent effects of the gap junction conduction-enhancing antiarrhythmic
      peptide rotigaptide (ZP123) on experimental atrial fibrillation in dogs.
AB  - BACKGROUND: Abnormal intercellular communication caused by connexin dysfunction
      may be involved in atrial fibrillation (AF). The present study assessed the
      effect of the gap junctional conduction-enhancing peptide rotigaptide on AF
      maintenance in substrates that result from congestive heart failure induced by 2
      week ventricular tachypacing (240 bpm), atrial tachypacing (ATP; 400 bpm for 3 to
      6 weeks), and isolated atrial myocardial ischemia. METHODS AND RESULTS:
      Electrophysiological study and epicardial mapping were performed before and after
      rotigaptide administration in dogs with ATP and congestive heart failure, as well
      as in similarly instrumented sham dogs that were not tachypaced. For atrial
      myocardial ischemia, dogs administered rotigaptide before myocardial ischemia
      were compared with no-drug myocardial ischemia controls. ATP significantly
      shortened the atrial effective refractory period (P=0.003) and increased AF
      duration (P=0.008), with AF lasting >3 hours in all 6-week ATP animals.
      Rotigaptide increased conduction velocity in ATP dogs slightly but significantly
      (P=0.04) and did not affect the effective refractory period, AF duration, or
      atrial vulnerability. In dogs with congestive heart failure, rotigaptide also
      slightly increased conduction velocity (P=0.046) but failed to prevent AF
      promotion. Rotigaptide had no statistically significant effects in sham dogs.
      Myocardial ischemia alone increased AF duration and impaired conduction (based on
      conduction velocity across the ischemic border and indices of conduction
      heterogeneity). Rotigaptide prevented myocardial ischemia-induced conduction
      slowing and AF duration increases. CONCLUSIONS: Rotigaptide improves conduction
      in various AF models but suppresses AF only for the acute ischemia substrate.
      These results define the atrial antiarrhythmic profile of a mechanistically novel
      antiarrhythmic drug and suggest that gap junction dysfunction may be more
      important in ischemic AF than in ATP remodeling or congestive heart failure
      substrates.

PMID- 17224478
TI  - Multimodality molecular imaging identifies proteolytic and osteogenic activities
      in early aortic valve disease.
AB  - BACKGROUND: Visualizing early changes in valvular cell functions in vivo may
      predict the future risk and identify therapeutic targets for prevention of aortic
      valve stenosis. METHODS AND RESULTS: To test the hypotheses that (1) aortic
      stenosis shares a similar pathogenesis to atherosclerosis and (2) molecular
      imaging can detect early changes in aortic valve disease, we used in vivo a panel
      of near-infrared fluorescence imaging agents to map endothelial cells,
      macrophages, proteolysis, and osteogenesis in aortic valves of
      hypercholesterolemic apolipoprotein E-deficient mice (30 weeks old, n=30).
      Apolipoprotein E-deficient mice with no probe injection (n=10) and wild-type mice
      (n=10) served as controls. Valves of apolipoprotein E-deficient mice contained
      macrophages, were thicker than wild-type mice (P<0.001), and showed early
      dysfunction detected by MRI in vivo. Fluorescence imaging detected uptake of
      macrophage-targeted magnetofluorescent nanoparticles (24 hours after injection)
      in apolipoprotein E-deficient valves, which was negligible in controls (P<0.01).
      Valvular macrophages showed proteolytic activity visualized by protease
      activatable near-infrared fluorescence probes. Ex vivo magnetic resonance imaging
      enhanced with vascular cell adhesion molecule-1-targeted nanoparticles detected
      endothelial activation in valve commissures, the regions of highest mechanical
      stress. Osteogenic near-infrared fluorescence signals colocalized with alkaline
      phosphatase activity and expression of osteopontin, osteocalcin, Runx2/Cbfa1,
      Osterix, and Notch1 despite no evidence of calcium deposits, which suggests
      ongoing active processes of osteogenesis in inflamed valves. Notably, the aortic
      wall contained advanced calcification. Quantitative image analysis correlated
      near-infrared fluorescence signals with immunoreactive vascular cell adhesion
      molecule-1, macrophages, and cathepsin-B (P<0.001). CONCLUSIONS: Molecular
      imaging can detect in vivo the key cellular events in early aortic valve disease,
      including endothelial cell and macrophage activation, proteolytic activity, and
      osteogenesis.

PMID- 17224480
TI  - Prevention of premature discontinuation of dual antiplatelet therapy in patients
      with coronary artery stents: a science advisory from the American Heart
      Association, American College of Cardiology, Society for Cardiovascular
      Angiography and Interventions, American College of Surgeons, and American Dental
      Association, with representation from the American College of Physicians.
AB  - Dual antiplatelet therapy with aspirin and a thienopyridine has been shown to
      reduce cardiac events after coronary stenting. However, many patients and
      healthcare providers prematurely discontinue dual antiplatelet therapy, which
      greatly increases the risk of stent thrombosis, myocardial infarction, and death.
      This advisory stresses the importance of 12 months of dual antiplatelet therapy
      after placement of a drug-eluting stent and educating the patient and healthcare
      providers about hazards of premature discontinuation. It also recommends
      postponing elective surgery for 1 year, and if surgery cannot be deferred,
      considering the continuation of aspirin during the perioperative period in high
      risk patients with drug-eluting stents.

PMID- 17224479
TI  - Sarcoplasmic reticulum calcium overloading in junctin deficiency enhances cardiac
      contractility but increases ventricular automaticity.
AB  - BACKGROUND: Abnormal sarcoplasmic reticulum calcium (Ca) cycling is increasingly
      recognized as an important mechanism for increased ventricular automaticity that
      leads to lethal ventricular arrhythmias. Previous studies have linked lethal
      familial arrhythmogenic disorders to mutations in the ryanodine receptor and
      calsequestrin genes, which interact with junctin and triadin to form a
      macromolecular Ca-signaling complex. The essential physiological effects of
      junctin and its potential regulatory roles in sarcoplasmic reticulum Ca cycling
      and Ca-dependent cardiac functions, such as myocyte contractility and
      automaticity, are unknown. METHODS AND RESULTS: The junctin gene was targeted in
      embryonic stem cells, and a junctin-deficient mouse was generated. Ablation of
      junctin was associated with enhanced cardiac function in vivo, and junctin
      deficient cardiomyocytes exhibited increased contractile and Ca-cycling
      parameters. Short-term isoproterenol stimulation elicited arrhythmias, including
      premature ventricular contractions, atrioventricular heart block, and ventricular
      tachycardia. Long-term isoproterenol infusion also induced premature ventricular
      contractions and atrioventricular heart block in junctin-null mice. Further
      examination of the electrical activity revealed a significant increase in the
      occurrence of delayed afterdepolarizations. Consistently, 25% of the junctin-null
      mice died by 3 months of age with structurally normal hearts. CONCLUSIONS:
      Junctin is an essential regulator of sarcoplasmic reticulum Ca release and
      contractility in normal hearts. Ablation of junctin is associated with aberrant
      Ca homeostasis, which leads to fatal arrhythmias. Thus, normal intracellular Ca
      cycling relies on maintenance of junctin levels and an intricate balance among
      the components in the sarcoplasmic reticulum quaternary Ca-signaling complex.

PMID- 17224481
TI  - Midface effects of the deep-plane vs the superficial musculoaponeurotic system
      plication face-lift.
AB  - OBJECTIVE: To determine if there is any observable difference in the midface of
      patients who have undergone a deep-plane face-lift vs a standard superficial
      musculoaponeurotic system (SMAS) plication face-lift. DESIGN: Preoperative and
      postoperative photographs of 25 patients undergoing each type of face-lift were
      rated by 3 independent and blinded observers. A 7-point scale was used to grade
      improvement in 5 areas on the face and neck: malar eminence, melolabial fold,
      jowls, cervicomental angle, and anterior neck banding. RESULTS: All 3 independent
      observers rated the patients who underwent a deep-plane face-lift as having a
      significantly better result (P<.01) in 2 of the measured locations; the observed
      improvements in the deep-plane group were twice those in the SMAS plication
      group. CONCLUSION: In our study of 50 patients, the deep-plane face-lift proved
      to have results that were clinically and statistically better than those of the
      SMASapplication face-lift in both the midface and the neck.

PMID- 17224482
TI  - A review of 25-year experience of nasal septal perforation repair.
AB  - OBJECTIVE: To report the long-term follow-up of 25 years of experience in 100
      consecutive cases of septal perforation (SP) repair using the technique of the
      senior author (F.P.). DESIGN: From 1981 to 2006, a total of 100 consecutive
      patients were surgically treated and followed up for 1 to 10 years. The medical
      records of 68 of the patients were retrospectively examined. Outcomes were
      assessed based on comparison of the results of preoperative and last follow-up
      assessment of SP size and symptoms. The SP repair technique consists of
      subperichondrial/periosteal dissection, rotation of nasal mucosa for tension-free
      closure, with no mucosa incision if possible, and a multilayer closure with
      interposition graft. RESULTS: The most common symptoms were nasal obstruction
      (72%), crusts (50%), and epistaxis (31%). Previous nasal surgery was the
      pathogenetic factor in 39 cases (57%). Fifty-two patients (76%) presented with
      SPs measuring 1.0 to 3.0 cm in diameter. The internal approach was used in 54
      cases (79%), and temporal muscle fascia and conchal cartilage were concomitantly
      used in 45 cases (66%). The great majority of patients (40 [59%]) received more
      than 5 years of follow-up. The success rate of closure was 97%. Two patients (3%)
      presented with reperforation measuring less than 1.0 cm in diameter. CONCLUSIONS:
      The senior author's SP repair technique is easily accomplished, provides good
      visualization, and is low in cost. Also, in our experience, the success rate of
      closure has been 97%.

PMID- 17224483
TI  - The effect of low-molecular-weight heparin on microvenous thrombosis in a rat
      model.
AB  - OBJECTIVE: To assess the impact of a low-molecular-weight heparin sodium,
      dalteparin sodium, on a thrombogenic microvenous anastomosis, using a randomized,
      blinded animal model. METHODS: Using male Sprague-Dawley rats, 70 IU/kg of
      dalteparin sodium (for the treatment group) or isotonic sodium chloride solution
      (for the control group) were administered subcutaneously in a blinded randomized
      fashion. Using microsurgical techniques, the femoral venous pedicle was isolated
      bilaterally. A tuck anastomosis was then performed on each side. Vessel patency
      was assessed periodically for 3 hours using a strip and refill test. Patency or
      thrombosis was confirmed by cutting the vessel proximal to the anastomosis and
      examining the lumen for thrombus. RESULTS: A total of 58 venous tuck anastomoses
      were performed. There was no difference in bleeding complications between the
      treatment and control groups. The control group had a thrombosis rate of 50%, and
      the treatment group had a thrombosis rate of 60%. The chi2 analysis does not
      indicate a statistical difference between these 2 groups (P = .59). CONCLUSION:
      Low-molecular-weight heparin, at standard therapeutic dosing, may not provide an
      adequate antithrombotic effect to prevent anastomotic thrombosis in free tissue
      transfer.

PMID- 17224484
TI  - Selective creation of thermal injury zones in the superficial musculoaponeurotic
      system using intense ultrasound therapy: a new target for noninvasive facial
      rejuvenation.
AB  - OBJECTIVES: To transcutaneously deliver intense ultrasound (IUS) energy to target
      the facial superficial musculoaponeurotic system (SMAS), to produce discrete
      thermal injury zones (TIZs) in the SMAS, and to demonstrate the relative sparing
      of adjacent nontargeted layers superficial and deep to the SMAS layer. METHODS:
      In 6 unfixed human cadaveric specimens, the SMAS layer was visualized and
      targeted using the ultrasound imaging component of the IUS device. Using 2 IUS
      handpieces, 202 exposure lines were delivered bilaterally in multiple facial
      regions by varying combinations of power and exposure time (0.5-8.0 J). Tissue
      was then excised and examined grossly and histologically for evidence of thermal
      injury using nitroblue tetrazolium chloride viability stain. RESULTS:
      Reproducible TIZs were produced selectively in the SMAS at depths of up to 7.8
      mm, and sparing of surrounding tissue including the epidermis. Higher energy
      settings and high-density exposure line pattern produced a greater degree of
      tissue shrinkage. CONCLUSIONS: In human cadaveric facial tissue, IUS can
      noninvasively target and selectively produce TIZs of reproducible location, size,
      and geometry in the SMAS layer. The ability to produce focused thermal collagen
      denaturation in the SMAS to induce shrinkage and tissue tightening has not been
      previously reported and has significant implications for aesthetic facial
      rejuvenation.

PMID- 17224485
TI  - Nasal base narrowing: the combined alar base excision technique.
AB  - OBJECTIVE: To evaluate the role of the combined alar base excision technique in
      narrowing the nasal base and correcting excessive alar flare. METHODS: The study
      included 60 cases presenting with a wide nasal base and excessive alar flaring.
      The surgical procedure combined an external alar wedge resection with an internal
      vestibular floor excision. All cases were followed up for a mean of 32 (range, 12
      144) months. Nasal tip modification and correction of any preexisting caudal
      septal deformities were always completed before the nasal base narrowing.
      RESULTS: The mean width of the external alar wedge excised was 7.2 (range, 4-11)
      mm, whereas the mean width of the sill excision was 3.1 (range, 2-7) mm.
      Completing the internal excision first resulted in a more conservative external
      resection, thus avoiding any blunting of the alar-facial crease. No cases of
      postoperative bleeding, infection, or keloid formation were encountered, and the
      external alar wedge excision healed with an inconspicuous scar that was well
      hidden in the depth of the alar-facial crease. Finally, the risk of notching of
      the alar rim, which can occur at the junction of the external and internal
      excisions, was significantly reduced by adopting a 2-layered closure of the
      vestibular floor (P = .01). CONCLUSIONS: The combined alar base excision resulted
      in effective narrowing of the nasal base with elimination of excessive alar
      flare. Commonly feared complications, such as blunting of the alar-facial crease
      or notching of the alar rim, were avoided by using simple modifications in the
      technique of excision and closure.

PMID- 17224486
TI  - Analysis of the physical properties of costal cartilage in a porcine model.
AB  - OBJECTIVE: To determine the impact of interventions on the degree of warping of
      costal cartilage. METHODS: The project was conducted at a large university animal
      research laboratory. The costal cartilage of eight 30-kg domestic pigs was
      harvested. The cartilage was cut into central and peripheral segments with a
      standard cutting die. Two sizes of rectangular cubes were compared. The central
      portions of costal cartilage were segmented and glued with octyl-2-cyanoacrylate.
      The shape of the cartilage was documented with both digital and film photography.
      The cartilage was placed into subdermal pockets on the dorsum of the pigs. The
      animals were killed at 4 weeks, and the cartilage was photographed. Adobe
      Photoshop software was used to measure the degree of warping. Statistical
      analysis was calculated by t test analysis. RESULTS: A total of 115 rectangular
      costal cartilage blocks were treated. Large blocks warped less than small blocks
      (P<.02). Centrally cut blocks warped less than peripherally cut blocks (P<.03).
      The octyl-2-cyanoacrylate incited a significant sterile inflammatory response
      such that the blocks could not be accurately assessed for warpage. CONCLUSION:
      Costal cartilage can be effectively used for grafting in rhinoplasty with minimal
      warping if large grafts from the central portion of cartilage are used.

PMID- 17224487
TI  - Patient satisfaction after closed reduction of nasal fractures.
AB  - OBJECTIVE: To evaluate the outcome of closed reduction from a patient's point of
      view, because there is increasing evidence that closed reduction of nasal
      fractures fails to address deformities of the cartilaginous nasal framework and
      the septum. METHODS: We performed a retrospective study of 62 patients who
      underwent a closed reduction of nasal fracture between July 1, 2002, and June 30,
      2005. All patients were interviewed regarding the esthetic and functional
      outcomes after closed reduction. RESULTS: Eighteen patients (29%) expressed
      dissatisfaction with the esthetic outcome of the reduction, and 18 (29%) said
      they would consider further surgery to correct the residual nasal deformity.
      CONCLUSIONS: A stringent preoperative assessment of the nasal fracture, other
      nasal deformities, and nasal function is essential before offering patients a
      simple closed reduction of their nasal fractures. A septorhinoplasty, as the
      definitive procedure, should be offered to patients when a closed reduction is
      deemed unable to address all deformities.

PMID- 17224488
TI  - Intraoral transposition of traumatic parotid duct fistula.
AB  - Parotid duct fistula is uncommon but difficult-to-treat complication that often
      results from a penetrating trauma. While there is general consensus in the
      literature as to the management of acute parotid injuries, treatment of chronic
      fistulas remains controversial. We review the current treatment options for
      parotid duct fistulas and describe an intraoral diversion technique to
      reestablish salivary flow in the setting of a nonfunctional parotid duct punctum.

PMID- 17224489
TI  - A simplified approach to midface aging.
AB  - We review herein our experience with subperiosteal midface-lifting under direct
      vision with a simple fixation technique. The technical aspects of the procedure
      are described in detail. A total of 121 patients underwent midface-lifting and
      meloplication with the 82/18 L-lactide/glycolide device (Coapt Endotine Midface
      ST 4.5; Coapt Technologies, Palo Alto, Calif) by both the senior (G.S.K.) and
      junior (R.N.H.) authors. The senior author's experience included 110 patients
      over a 26-month period. Thirty-two of these cases were isolated procedures. The
      other 78 were performed in conjunction with various procedures, most commonly
      rhytidectomy. There were no revisions during this period. Two cases of
      "puckering" were noted. Both were immediately corrected, one with fat injection
      and one with poly-L-lactic acid injection (Sculptra; Dermik Aesthetics,
      distributed by Besse Medical Supply, West Chester, Ohio). The junior author's
      experience included 11 cases over an 8-month period. Two cases of asymmetry were
      noted. One was corrected with fat injection, and the other required revision.
      Subperiosteal midface-lifting and meloplication using the Coapt Endotine Midface
      ST 4.5 device is a simple, effective technique that can be quickly learned and
      applied.

PMID- 17224490
TI  - Direct excision of the turkey jowl deformity: a review of 100 consecutive cases.
AB  - OBJECTIVE: The aging of the neck is a combination of accumulated submental fat,
      platysmal banding, and redundant skin. Traditional face- and neck-lifting
      procedures successfully address these components. Unfortunately, the cost, both
      in terms of downtime and expense, often becomes prohibitive for a large section
      of the interested patient population. For select male patients, direct excision
      of the turkey jowl deformity with a straight-line closure offers a novel
      alternative. DESIGN: A review of 100 consecutive cases of direct excision of
      turkey jowl deformity procedures was performed. Minimal follow-up was 1 year. All
      surgical procedures were performed in the office setting with local anesthesia.
      RESULTS: Eight patients had extrusions of suture without recurrence of banding.
      Four patients required steroid injections for mild scar hypertrophy; 2 of these
      patients requested minor scar revisions 1 year later. There were no cases of
      postoperative bleeding, infection, or nerve injury. All 100 patients were
      satisfied with the overall cosmesis, and none had revision jowl surgery.
      CONCLUSIONS: Direct excision of the turkey jowl with a straight-line closure
      offers a major improvement in the aging neck with minimal downtime, expense, and
      complication rate. This procedure can be easily accomplished and safely performed
      in an office environment.

PMID- 17224491
TI  - Injectable calcium hydroxyapatite filler for minimally invasive delayed treatment
      of traumatic enophthalmos.

PMID- 17224494
TI  - Request for commentaries.

PMID- 17224492
TI  - Repair of orbital floor fractures with SupraFOIL Smooth Nylon Foil.

PMID- 17224495
TI  - Quality of life and morbidity after permanent sacral nerve stimulation for fecal
      incontinence.
AB  - HYPOTHESIS: Permanent sacral nerve stimulation (SNS) is a promising emerging
      treatment for fecal incontinence. However, there is little data on morbidity and
      quality of life (QOL) during long-term stimulation. DESIGN: Prospective trial to
      assess morbidity and QOL in patients treated with SNS. Median follow-up was 13
      months (range, 1-42 months). SETTING: University hospital providing primary,
      secondary, and tertiary care. PATIENTS: Between December 2001 and July 2005, SNS
      was tested in 44 patients (30 women), with a median age of 65 years (range, 15-88
      years). INTERVENTIONS: Percutaneous nerve evaluation and permanent insertion of
      an implantable pulse generator. MAIN OUTCOME MEASURES: Morbidity, stool diary,
      and Wexner Score for fecal incontinence; Hanley Score for urinary incontinence;
      and Gastrointestinal Quality of Life Index, the 36-item short form health survey,
      and the Royal London Hospital questionnaire for QOL. RESULTS: A permanent
      stimulator was implanted in 37 patients (84%). Eight patients (22%) experienced
      complications that required surgical intervention. (A successful restimulation
      was possible for 5 of those patients.) Adverse effects of SNS were remedied in 5
      patients by reprogramming the stimulator. Wexner Scores decreased from a median
      of 16 points preoperatively (range, 6-20), to a median of 5 points
      postoperatively (range, 0-13; P<.001). The median number of involuntary stool
      losses and for urge defecations also decreased significantly. Significant
      improvement in QOL was found in both generic and incontinence-specific
      questionnaires (P<.05). The success rate of SNS was 77% (34 of 44 patients) and
      92% (34 of 37) in patients with permanent implantation. CONCLUSIONS: The
      minimally invasive technique of SNS is safe and effective. Most adverse effects
      can be easily remedied. Our data demonstrate that SNS significantly improves
      patients' QOL, including their physical and psychological well-being.

PMID- 17224496
TI  - Surgeon characteristics and variations in treatment for early-stage breast
      cancer.
AB  - HYPOTHESIS: Adherence to National Institutes of Health consensus statement
      recommendations for early-stage breast cancer will vary by surgeon
      characteristics. DESIGN: Secondary data analysis using the Surveillance,
      Epidemiology, and End Results national tumor registry linked with Medicare claims
      data. Logistic regression was used to analyze data on a cohort of 1045 surgeons
      who operated on 9449 Medicare patients with early-stage breast cancer. MAIN
      OUTCOME MEASURE: Care adherent to the 1990 National Institutes of Health
      consensus statement recommendations. RESULTS: Surgeon age and specialty were not
      associated with adherent care overall, nor among breast-conserving surgery or
      mastectomy subgroups. Patients of higher-volume surgeons were significantly more
      likely to undergo adherent care overall because of greater use of lymph node
      dissection among women who received either breast-conserving surgery or
      mastectomy. Patients of female surgeons and surgeons with a medical school
      affiliation were less likely to undergo adherent care overall, which was related
      to greater use of breast-conserving surgery and lesser use of lymph node
      dissection among patients who underwent breast-conserving surgery. CONCLUSIONS:
      Several surgeon characteristics are significantly associated with variations in
      breast cancer treatment received. These results warrant further investigation
      into the association between these surgeon characteristics and cancer care
      outcomes.

PMID- 17224497
TI  - Surgeon and hospital characteristics as predictors of major adverse outcomes
      following colon cancer surgery: understanding the volume-outcome relationship.
AB  - HYPOTHESIS: Although numerous studies have demonstrated an association between
      surgical volume and improved outcome in cancer surgery, the specific structures
      and mechanisms of care that are associated with volume and lead to improved
      outcomes remain poorly defined. We hypothesize that there are modifiable surgeon
      and hospital characteristics that explain observed volume-outcome relationships.
      DESIGN: Retrospective cohort study. SETTING: Surveillance, Epidemiology, and End
      Results cancer registry areas. PATIENTS: Patients aged 66 years and older,
      diagnosed and surgically treated for stage I, II, or III colon cancer between
      1992 and 1996 (n = 22 672). MAIN OUTCOME MEASURES: Thirty-day postoperative
      mortality and 30-day postoperative procedural interventions, including
      reoperation and image-guided percutaneous procedures. RESULTS: Surgeon volume,
      but not hospital volume, is a significant predictor of postoperative procedural
      intervention (adjusted odds ratio for very high-volume surgeons vs low-volume
      surgeons, 0.79; 95% confidence interval, 0.64-0.98). In the unadjusted analyses,
      high hospital volume (odds ratio, 0.67; 95% confidence interval, 0.56-0.81) and
      very high hospital volume (odds ratio, 0.65; 95% confidence interval, 0.54-0.79)
      is associated with lower postoperative mortality. Postoperative procedural
      intervention is not a significant mediator of the relationship between hospital
      volume and mortality. A single variable-the presence of sophisticated clinical
      services-was the most important explanatory variable underlying the relationship
      between hospital volume and mortality. CONCLUSIONS: Very high surgeon volume is
      associated with a reduction in surgical complications. However, the association
      between increasing hospital volume and postoperative mortality appears to derive
      mainly from a full spectrum of clinical services that may facilitate the prompt
      recognition and treatment of complications.

PMID- 17224498
TI  - Long-term results of endovascular abdominal aortic aneurysm treatment with the
      first generation of commercially available stent grafts.
AB  - HYPOTHESIS: Little information about the long-term results of endovascular
      abdominal aortic aneurysm repair is available. This study was performed to
      evaluate the long-term data of patients treated with the first generation of
      commercially available stent grafts. DESIGN: Multicenter registry. SETTING: Sixty
      two European centers that participated in the EUROSTAR (EUROpean collaborators on
      Stent-graft Techniques for abdominal aortic Aneurysm Repair) registry. PATIENTS:
      A total of 1190 patients with a follow-up of up to 8 years, who underwent
      endovascular abdominal aortic aneurysm repair with a stent graft (Stentor or
      Vanguard). INTERVENTION: Elective endovascular abdominal aortic aneurysm repair.
      MAIN OUTCOME MEASURES: The morbidity and mortality data of patients treated with
      the first-generation stent graft who enrolled in the EUROSTAR registry were
      analyzed. Incidence rates of complications were calculated to quantify annual
      risks. Life-table analyses and multivariate Cox proportional hazards models were
      used for the survival analysis. RESULTS: Conversion to open repair, aneurysm
      rupture, all-cause death, and aneurysm-related death occurred in 7.1%, 2.4%,
      19.9%, and 3.0% of the patients, respectively. The cumulative percentage of the
      combined outcome event, conversion-free and rupture-free survival, after 8 years
      was 48.0%. Procedure-related complications that frequently occurred were endoleak
      (13.0 cases per 100 patient-years), stenosis/thrombosis (4.6 cases per 100
      patient-years), and stent migration (4.3 cases per 100 patient-years).
      CONCLUSIONS: Patients treated with the first generation of stent grafts will need
      lifelong surveillance because of a considerable risk of late complications. How
      these findings translate to the outcome of newer-generation stent grafts is
      unknown. For this reason, vigilant surveillance remains indicated in all patients
      who undergo endovascular abdominal aortic aneurysm repair.

PMID- 17224499
TI  - Optimizing choledocholithiasis management: a cost-effectiveness analysis.
AB  - HYPOTHESIS: Endoscopic retrograde cholangiopancreatography (ERCP) is more cost
      effective for managing incidental choledocholithiasis (CDL) after laparoscopic
      cholecystectomy and intraoperative cholangiogram (LC/IOC) than laparoscopic
      common bile duct exploration (LCBDE). DESIGN: A cost-effectiveness analysis was
      performed to compare ERCP with LCBDE. Sensitivity analyses were performed to
      determine the key contributors to cost-effectiveness between the 2 treatment
      options. SETTING: Costs were approached from the institutional perspective
      considering a typical patient undergoing LC/IOC at a large referral center.
      PATIENTS: The base case patient evaluated was a woman 18 years of age or older
      with symptomatic cholelithiasis and incidental CDL discovered at the time of
      LC/IOC. INTERVENTIONS: Endoscopic retrograde cholangiopancreatography with
      drainage procedure performed after LC/IOC or LCBDE during LC/IOC. MAIN OUTCOME
      MEASURES: Costs, quality-adjusted life years gained, mean cost-effectiveness
      ratios, and incremental cost-effectiveness ratios. RESULTS: In the base case
      analysis, ERCP was the optimal treatment choice with a cost of $24 300 for 0.9
      quality-adjusted life years gained compared with $28 400 and 0.88 quality
      adjusted life years for LCBDE. Endoscopic retrograde cholangiopancreatography
      remained the optimal strategy for CDL in multiway probabilistic sensitivity
      analysis. If LCBDE were performed and the cost of a potential operative case lost
      was $3100 or less and the cost of ERCP hospitalization was $18 000 or more, then
      LCBDE became the preferred treatment for CDL. CONCLUSIONS: Endoscopic retrograde
      cholangiopancreatography was both less costly and more effective than LCBDE.
      Factors important to choosing the best strategy for CDL management included the
      cost of a potential case lost due to LCBDE performance and the cost of ERCP
      hospitalization.

PMID- 17224500
TI  - Cost-utility analysis applied to the treatment of burn patients in a specialized
      center.
AB  - OBJECTIVE: To discover the total costs and quality of life of burn patients in a
      specialist center classified by diagnosis-related groups (DRGs). DESIGN:
      Prospective study of 5-year follow-up from January 1, 1997, through December 31,
      2001. SETTING: Burn Center of Valencia. PATIENTS: A total of 898 patients treated
      at the Burn Center of Valencia. MAIN OUTCOME MEASURES: Hospital, extrahospital,
      caregiving, labor, and social costs of the burn patients grouped by DRG (code
      457: extensive burns without operating room procedure; code 458: nonextensive
      burns with skin graft; code 459: nonextensive burns with wound debridement or
      other operating room procedure; code 460: nonextensive burns without operating
      room procedure; or code 472: extensive burns with operating room procedure) were
      studied. The costs were compared with those that the DRG system assigns. The
      quality of life of the patients at the end of the follow-up period was also
      studied. To measure quality of life, the EuroQol 5-Dimensions survey was used.
      Utility calculations and cost-utility analysis were undertaken according to life
      expectancy. RESULTS: The number of quality-adjusted life-years produced by the
      center was 13 577, with a mean quality-of-life level on release from the study of
      0.87. The mean cost per patient, including the social and labor costs, was $95
      551, with health care costs amounting to only 10%. The mean cost per quality
      adjusted life-year was $686. CONCLUSIONS: The labor costs were the most important
      and amounted to 56%; together with the social costs, these constituted 85% of the
      total costs. The DRG code 456 was an option dominated by the remaining DRG codes
      458 through 460 and 472. Given the high costs of treating burn patients, a clear
      health care policy is urgently needed.

PMID- 17224501
TI  - Laparoscopic appendectomy in children: use of the endoloop vs the endostapler.
AB  - HYPOTHESIS: Two techniques are used for laparoscopic appendectomy (LA): division
      of the mesoappendix with the harmonic scalpel and ligation of the appendix with
      an endoloop (EL), or division of the mesoappendix and appendix with an
      endostapler (ES). Using an ES is a cost-effective technique that provides an
      outcome benefit in children who require appendectomy. DESIGN: Case series.
      SETTING: Academic, tertiary care children's hospital. PATIENTS: Seventy-five
      children who underwent LA from January 1, 2002, to March 31, 2004. INTERVENTION:
      Laparoscopic appendectomy. MAIN OUTCOME MEASURES: Age, diagnosis, length of stay,
      surgical time, total operating room time, complications, and instrumentation
      costs were compared between the EL and ES groups. RESULTS: There was no
      significant difference in age, length of stay, perforated, gangrenous, or acute
      appendicitis diagnoses, or complications between the groups. The surgical time
      and total operating room time for LA in children in the ES group were
      significantly shorter than in children in the EL group by 15% and 17%,
      respectively (P<.05). The disposable equipment costs for LA were $201 per case in
      the ES group vs $400 per case in the EL group. The mean 14.9-minute increase in
      total operating room time in children in the EL group resulted in $373 of
      additional operating room and anesthesia costs. The decreased disposable
      equipment costs and shorter surgical time of LA in the ES group led to cost
      savings of $572 per case as compared with children who underwent LA with an EL.
      CONCLUSIONS: There is no significant difference in outcome between children who
      undergo LA with an EL or with an ES. However, this study supports the use of the
      ES for LA as a more cost-effective technique that is associated with reduced
      surgical time.

PMID- 17224502
TI  - Tumor size and operative risks of extended right-sided hepatic resection for
      hepatocellular carcinoma: implication for preoperative portal vein embolization.
AB  - HYPOTHESIS: Major hepatic resection for hepatocellular carcinoma (HCC) is
      associated with high operative morbidity and mortality, especially in patients
      with underlying chronic liver disease. The present study evaluated the factors
      associated with increased operative risks in patients who underwent extended
      right-sided hepatic resection for HCC. DESIGN: Retrospective study. SETTING:
      Tertiary referral center. PATIENTS: A retrospective study was performed on 172
      patients who underwent extended right-sided hepatic resection of more than 4
      Couinaud segments for HCC during a 16-year period (January 1, 1989, to December
      31, 2004) to evaluate the clinical factors associated with operative morbidity
      and mortality. MAIN OUTCOME MEASURE: Risk factors associated with hospital
      mortality and major operative morbidity. RESULTS: The overall major morbidity and
      hospital mortality rates were 14.0% and 8.1%, respectively. On multivariate
      analysis, small tumor size, conventional-approach hepatectomy, Child-Pugh grade B
      cirrhosis, and preexisting tumor rupture were the independent factors
      significantly associated with an increased risk of operative mortality.
      Discriminant analysis showed that a tumor size smaller than 10 cm significantly
      increased the risk of operative mortality compared with larger tumors (17.2% vs
      3.5%; P = .046). CONCLUSIONS: Anterior approach is the preferred technique for
      extended right-sided hepatic resection for HCC. Increased risk of operative
      mortality was identified in patients who had a small tumor, which was associated
      with the resection of a large volume of functioning liver parenchyma.
      Preoperative portal vein embolization should be considered in this group of
      patients to enhance atrophy of the right lobe and hypertrophy of the future liver
      remnant to minimize the operative risk.

PMID- 17224503
TI  - Benefit of surgical treatment of lung metastasis in soft tissue sarcoma.
AB  - HYPOTHESIS: Patients with pulmonary metastatic soft tissue sarcoma benefit from
      resection, with long-term cure possible. DESIGN: Retrospective medical records
      review. SETTING: Academic tertiary care center. PATIENTS: Between January 1,
      1991, and December 31, 2002, 61 patients (33 men and 28 women; median age at
      initial diagnosis, 42 years [age range, 18-74 years]) were surgically treated for
      pulmonary metastases of soft tissue sarcoma at University Hospital, Hamburg
      Eppendorf, Germany. INTERVENTIONS: Sternotomy or anterior lateral thoracotomy was
      performed for metastasectomy, including wedge resection or lobectomy. MAIN
      OUTCOME MEASURE: The effects of clinical and pathologic factors on disease
      specific survival were analyzed using the log rank test and a multivariate Cox
      proportional hazards model. RESULTS: Primary tumor size was pT1 in 13 patients
      and pT2 in 48 patients. The differentiation was high in 7 patients, intermediate
      in 19 patients, and low in 35 patients. The mean number of resected pulmonary
      metastatic lesions was 5 (range, 1-48). An anterolateral thoracotomy was
      performed in 39 patients, and sternotomy in 22 patients. There were no
      significant postoperative complications that required surgical revision. The
      perioperative mortality was 0%. At a mean follow-up of 60 months, the mean
      survival time after metastasectomy was 33 months (range, 2-125 months). The 5
      year survival was 25%. The number of resected lung metastatic lesions had no
      prognostic relevance (P = .37). CONCLUSIONS: Patients with lung metastasis from
      soft tissue sarcomas benefit from surgical excision. This treatment has low
      complication rates and has a favorable influence on the course of the disease.
      Long-term survival is possible even when recurrent pulmonary disease is resected.

PMID- 17224504
TI  - Rural trauma recidivism: a different disease.
AB  - HYPOTHESIS: Unlike the well-characterized urban trauma recidivist (RC), factors
      associated with the rural RC remain undefined. In an attempt to devise
      preventative strategies, we theorized that the rural RC profile would be similar
      to that of urban counterparts. DESIGN: Retrospective review. SETTING: Rural,
      university-affiliated, level I trauma center. PATIENTS: All trauma patients
      admitted between January 1, 1994, and December 30, 2002. INTERVENTIONS:
      Identification and characterization of rural trauma RCs. MAIN OUTCOME MEASURES:
      Trauma recidivism incidence, risk factors, and cost. RESULTS: Of 15 370
      consecutive admissions, 528 (3.4%) were RCs. Demographic comparisons to a non-RC
      cohort demonstrated rural RCs to be significantly older (mean +/- SD age, 55.9 +/
      24.8 vs 39.7 +/- 24.1 years), disproportionately white (65.2% [344/528] vs 56.5%
      [8386/14 842]), and more likely female (49.1% [259/528] vs 37.3% [5537/14 842])
      (P<.001 for all). Clinical comparisons revealed significant associations between
      recidivism and substance abuse. The percentage of positive blood ethanol screen
      results (58.7% [310/528] vs 39.9% [5923/14 842]) and the mean +/- SD blood
      ethanol content (132.1 +/- 139.9 mg/dL [28.7 +/- 30.4 mmol/L] vs 69.5 +/- 114.4
      mg/dL [15.1 +/- 24.8 mmol/L]) were higher for RCs (P<.001 for both). In addition,
      cocaine use was significantly higher in the RC cohort (6.4% [34/528] vs 4.1%
      [607/14 842]; P=.02). The total cost for all RC admissions exceeded $7 million.
      CONCLUSIONS: The rural RC profile is strikingly different from urban
      counterparts. The common feature seems to be substance abuse. Correspondingly,
      prevention strategies for recidivism must be considerably different among rural
      and urban populations.

PMID- 17224505
TI  - Controversies in the current management of lumbar hernias.
AB  - BACKGROUND: Abdominal wall surgery has changed dramatically in recent years. The
      current management of lumbar hernias should reflect the development of modern
      imaging techniques and new forms of noninvasive treatment. OBJECTIVE: To review
      and update knowledge on lumbar hernias. DATA SOURCES: Literature review using
      MEDLINE with the key words "lumbar hernia" for the years 1950 through 2004. For
      an analysis prior to this date (1750-1950), we used cases reported by Thorek. Our
      own study of 28 patients was also included. STUDY SELECTION: All articles
      reporting clinical cases on lumbar hernia. DATA EXTRACTION: Two reviewers
      analyzed the epidemiological, clinical, and treatment data of the articles. DATA
      SYNTHESIS: One hundred thirty-five clinical case articles and 8 studies with more
      than 5 patients, together with our personal experience of 28 cases, were
      analyzed. Nine percent of acquired lumbar hernia cases presented for emergency
      surgery, which means that a clinical diagnosis was completed with computed
      tomography in more than 90% of the cases. None of the published classifications
      has a therapeutic orientation. We present an original classification based on 6
      categories and 4 types. In our study, there was a predominance of incisional
      hernias (79%), with no difference with regard to sex or location but with a
      predominance in the upper space (47%). Laparoscopic treatment accounts for 9% of
      the publications' cases and there is only 1 prospective comparative study.
      CONCLUSIONS: The use of a complete classification and tomography must be standard
      practice in the preoperative protocol of patients with lumbar hernia. The
      laparoscopic approach seems to be the best option for treating small or moderate
      defects; open surgery can be reserved for large defects and to salvage failures
      with the laparoscopic approach.

PMID- 17224506
TI  - Mediators or markers of injury, inflammation, and infection (harbingers of doom
      or predictors of disaster) and biologic puzzles or ambiguities.

PMID- 17224508
TI  - Image of the month--pedunculated hepatocellular carcinoma.

PMID- 17224509
TI  - Image of the month--perforated stercoral ulcer.

PMID- 17224510
TI  - Antibiotic use and delayed source control in acute appendicitis.

PMID- 17224511
TI  - Delayed appendectomy for acute appendicitis.

PMID- 17224512
TI  - Bowel necrosis associated with early jejunal tube feeding.

PMID- 17224513
TI  - Standards for ethical publication.

PMID- 17224515
TI  - Surgical wound complications after intensive chemoradiotherapy for advanced
      squamous cell carcinoma of the head and neck.
AB  - OBJECTIVE: To define the rate of complications from surgery following intensive
      chemoradiotherapy in patients with advanced squamous cell carcinoma of the head
      and neck. DESIGN: The medical records of 131 consecutive patients treated with a
      combination of chemotherapy and radiation therapy for head and neck squamous cell
      carcinoma from 1995 through 2002 were reviewed. Thirty-eight patients underwent
      50 surgical procedures. Thirty-seven neck dissections were performed either for
      persistent disease, initial neck stage N2 or greater, recurrent disease, or
      electively as part of salvage surgery for the primary site. Thirteen salvage
      operations were performed for persistent or recurrent disease at the primary
      site. SETTING: Academic tertiary care referral center. PATIENTS: A total of 131
      consecutive patients treated with a combination of chemotherapy and radiation
      therapy for head and neck squamous cell carcinoma (mean age at diagnosis, 53
      years). MAIN OUTCOME MEASURE; Rate of complications from surgery. RESULTS: Wound
      complications occurred in 4 (11%) of 38 patients and 5 (10%) of 50 procedures.
      Major wound complications occurred in 3 (8%) of 38 patients. Minor wound
      complications occurred in 2 patients (5%). CONCLUSION: Surgery can be safely
      performed after intensive chemoradiotherapy.

PMID- 17224516
TI  - Effects of the integrin-linked kinase inhibitor QLT0267 on squamous cell
      carcinoma of the head and neck.
AB  - OBJECTIVE: To study the expression of integrin-linked kinase (ILK) in human
      squamous cell carcinoma of the head and neck (SCCHN) tumor specimens and cell
      lines and the efficacy of the novel small molecule QLT0267. DESIGN:
      Immunohistochemical analysis of 17 SCCHN tumor tissue specimens and 3 normal
      tongue tissue specimens for ILK expression and in vitro analysis of the
      effectiveness of QLT0267 on SCCHN cells. SETTING: Academic medical center. MAIN
      OUTCOME MEASURES: Expression levels of ILK in SCCHN tumor specimens and cell
      lines and the efficacy of QLT0267 in inhibiting cell growth and inducing
      apoptosis in SCCHN cell lines. RESULTS: Most SCCHN tumor specimens stained for
      ILK, whereas none of the 3 normal tongue tissue specimens stained for ILK.
      Integrin-linked kinase was expressed in all 6 SCCHN cell lines tested. In 4 pairs
      of normal and SCCHN tumor specimens, ILK expression and activity were higher in
      most tumor samples tested. A kinase assay showed that QLT0267 inhibited the ILK
      activity of 2 SCCHN cell lines (TU167 and MDA1986). Modified tetrazolium salt 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DNA fragmentation
      ladder, and TUNEL (terminal deoxynucleotidyl transferase-mediated biotin
      deoxyuridine triphosphate nick-end()labeling) assays showed that QLT0267
      inhibited cell growth and induced apoptosis in these 2 cell lines. A dose
      dependent decrease in Akt phosphorylation was observed for these 2 cell lines on
      treatment with QLT0267. CONCLUSIONS: Integrin-linked kinase is overexpressed in
      SCCHN tumor specimens. Targeting ILK with the small-molecule ILK inhibitor
      QLT0267 inhibits cell growth and induces apoptosis in SCCHN cell lines by
      reducing ILK activity and Akt phosphorylation. Integrin-linked kinase may be an
      attractive target for molecular therapy with which to enhance treatment of SCCHN.

PMID- 17224517
TI  - Using comorbidity indexes to predict costs for head and neck cancer.
AB  - OBJECTIVE: To determine whether the general Charlson Comorbidity Index (CCI) and
      the head and neck cancer-specific Washington University Head and Neck Cancer
      Comorbidity Index (WUHNCCI) were useful for predicting cost of treatment for
      elderly patients with head and neck cancer. DESIGN: Retrospective, observational
      study. PATIENTS: A total of 1780 Medicare patients with head and neck cancer, who
      were treated between 1984 and 1994, were analyzed using the Surveillance,
      Epidemiology, and End Results (SEER)-Medicare-linked database. MAIN OUTCOME
      MEASURES: Total Medicare payments were accumulated for each patient up to 1 and 5
      years. Linear regression was used to estimate the impact of the comorbidity
      indexes on costs, controlling for demographics, site, stage, and treatment
      modality. RESULTS: Neither the WUHNCCI nor the CCI was significantly associated
      with 1-year costs. However, the effect of the WUHNCCI on 5-year costs was
      statistically significant (P<.001). A 1-point increase in the WUHNCCI from 4 to 5
      was associated with an increase in 5-year costs of $2105. A 1-point increase in
      the WUHNCCI from 9 to 10 was associated with an increase in 5-year costs of
      $2837. CONCLUSION: These results suggest that comorbidity indexes for head and
      neck cancer may be useful for prognostication of patient outcomes and predicting
      costs.

PMID- 17224518
TI  - Head and neck cancer recurrence and mortality in nonselective cyclooxygenase
      inhibitor users.
AB  - OBJECTIVE: To determine whether ongoing use of a cyclooxygenase (COX) inhibitor
      is associated with a reduction in mortality and disease recurrence after head and
      neck cancer treatment. DESIGN: Retrospective case-control study. Patients A total
      of 325 potential subjects with head and neck squamous cell carcinoma were
      identified using an electronic patient database. Main Outcome Measure The rate of
      COX inhibitor use among patients who had died or whose disease had recurred
      (cases) was compared with the rate of use among survivors or those without
      recurrence (controls). The comparison was controlled for tumor site, tumor stage,
      treatment received, age, sex, race, smoking, and alcohol use. RESULTS: The 325
      patients were compared by logistic regressions, with recurrence rate and survival
      status as the dependent variables. There was no difference in COX inhibitor
      exposure between patients with recurrence and those with no recurrence (P = .42)
      or between survivors and those who died of disease (P = .66). The median survival
      of COX inhibitor users, however, was 96 months, compared with 47 months in
      nonusers. The only independent variable with a significant impact on recurrence
      and survival was tumor stage at the time of diagnosis. CONCLUSIONS: Although
      preliminary in vitro studies suggest an antitumor effect of COX inhibitors in
      head and neck cancer, this study found no difference in head and neck cancer
      recurrence or survival in nonselective COX inhibitor users vs nonusers. A
      randomized, double-blinded controlled trial is needed to determine if COX
      inhibitors are an effective chemopreventive therapy in patients with head and
      neck cancer.

PMID- 17224519
TI  - Retronasal and orthonasal olfactory ability after laryngectomy.
AB  - OBJECTIVE: To characterize orthonasal and retronasal olfactory ability in
      patients who have had a total laryngectomy (TL). DESIGN: Prospective
      psychophysical evaluation of orthonasal and retronasal olfactory function.
      SETTING: Academic center outpatient clinic. PATIENTS: Volunteer sample of 36
      subjects who underwent laryngectomy 0.5 to 25.0 years after TL (median, 3.5
      years) and 36 age-, sex-, and smoking history-matched controls. MAIN OUTCOME
      MEASURES: Scores on established psychophysical tests of orthonasal and retronasal
      olfaction and self-rating scores of smell assessed with a visual analog scale.
      RESULTS: Assessment of orthonasal olfactory ability yielded a mean composite
      score of 4.3 (maximum score, 7) for the TL group and 5.3 for the control group (P
      = .002). Evaluation of retronasal olfactory ability resulted in a mean score of
      11.0 (maximum score, 20) for the TL group vs 14.3 for the control group (P<.001).
      The mean self-rating scores of smell were 2.9 and 6.6 (maximum score, 10) for the
      TL and control groups, respectively (P<.001). Self-ratings of smell positively
      correlated with orthonasal (r(S) = 0.42; P<.001) and retronasal (r(S) = 0.50;
      P<.001) olfactory ability. CONCLUSIONS: Laryngectomy is associated with
      measurable decreases in olfactory function that are also subjectively perceived.
      Quantification of decrements in orthonasal and retronasal olfactory function can
      be used to characterize the severity of hyposmia and to assess the potential for,
      and efficacy of, olfactory rehabilitation. Although self-assessment with a simple
      visual analog scale successfully identifies many laryngectomy patients who have
      objective evidence of olfactory dysfunction, further investigation is necessary
      to evaluate and compare its validity and reliability with other available survey
      instruments that purport to measure olfaction.

PMID- 17224521
TI  - Acellular dermal matrix grafts for prevention of microarterial thrombophlebitis.
AB  - OBJECTIVE: To examine the role of acellular dermal matrix grafts for prevention
      of microarterial anastomotic thrombophlebitis. DESIGN: Bilateral femoral artery
      microvascular anastomoses were created in the field of established wounds
      infected with Staphylococcus aureus in 12 rats. In each animal, 1 femoral
      microarterial anastomosis was wrapped with an acellular dermal matrix graft, and
      the contralateral femoral anastomosis was left unprotected. The incidence of
      femoral artery thrombosis was determined after 4 days by wound reexploration.
      SETTING: David Geffen School of Medicine, University of California, Los Angeles.
      MAIN OUTCOME MEASURE: The patency of femoral artery anastomoses was determined
      after 4 days by wound reexploration. RESULTS: The incidence of femoral artery
      thrombosis in vessels wrapped with acellular dermal matrix grafts was 17%. The
      incidence of femoral artery thrombosis in unprotected vessels was 100%. This
      difference was statistically significant (P<.05). CONCLUSION: Acellular dermal
      matrix grafts seem to have a protective effect in the prevention of acute
      thrombophlebitis when arterial microvascular anastomoses are performed in
      infected surgical fields.

PMID- 17224520
TI  - Combined endoscopic and open approach to the removal of expandable metallic
      tracheal stents.
AB  - OBJECTIVES: To review complications of indwelling tracheal stents and to describe
      a technique of stent removal using a combined open and endoscopic approach.
      DESIGN: Descriptive case series. SETTING: Medical University of South Carolina.
      PATIENTS: Six patients were identified who had undergone combined open and
      endoscopic removal of indwelling tracheal stents. Coated (4 patients) and
      uncoated (2 patients) expandable metal stents had been present for an average
      time of 24 months (range, 5-60 months) before removal. MAIN OUTCOME MEASURES:
      Medical comorbidities, characteristics of the underlying airway lesion (origin,
      type, and length), stent characteristics (type and duration), and the
      presentation and management of stent-related complications. RESULTS: All patients
      presented with worsening dyspnea and/or stridor, with 3 requiring intubation.
      Stent removal was performed in the operating room and consisted of initial
      exposure of the trachea for emergency airway access, removal of the indwelling
      stent under bronchoscopic and transtracheal guidance, and tracheotomy. Two
      patients experienced desaturations of more than 25% during the procedure, and 2
      patients had stents that could be only partially removed. Five patients
      subsequently received Montgomery T-tubes without complications after a mean
      follow-up of 23 months (range, 6-40 months). CONCLUSIONS: Indwelling tracheal
      stents are becoming increasingly common in the management of benign airway
      stenosis. The stents frequently occlude with granulation tissue and may require
      removal. A combined open and endoscopic removal maximizes airway protection and
      minimizes potential complications.

PMID- 17224522
TI  - Robotic surgery in the pediatric airway: application and safety.
AB  - OBJECTIVE: To assess the application and safety of transoral robotic surgery in
      the pediatric airway. DESIGN: An institutional review board-approved study.
      Experimental laryngeal surgery was performed on 4 pediatric cadaver larynxes as
      controls. Application of robotic equipment for laryngeal surgery was attempted on
      5 patients. SETTING: Tertiary care pediatric medical center. PATIENTS: Five
      patients with laryngeal cleft and 4 pediatric cadaver larynxes. INTERVENTIONS:
      (1) The da Vinci Surgical Robot (Intuitive Surgical Inc, Sunnyvale, Calif) was
      used on 4 cadaver larynxes and assessed for the dexterity, precision, and depth
      perception that it allowed the surgeon during laryngeal surgery. Procedures were
      documented with still and video photography. (2) The da Vinci Surgical Robot was
      used through a transoral approach to attempt repair of a laryngeal cleft in 5
      pediatric patients who were under spontaneously breathing general anesthesia.
      RESULTS: (1) Use of the surgical robot on cadaver larynxes provided great
      dexterity and precision, delicate tissue handling, good 3-dimensional depth
      perception, and relatively easy endolaryngeal suturing. (2) The surgical robot
      could not be used for repair of laryngeal cleft on 3 patients owing to limited
      transoral access. However, 1 patient with a type 1 laryngeal cleft and 1 patient
      with a type 2 laryngeal cleft underwent transoral robotic repair with great
      success. CONCLUSIONS: Surgical robots provide the ability to manipulate
      instruments at their distal end with great precision, increased freedom of
      movement, and excellent 3-dimensional depth perception. The size of the equipment
      can be a limiting factor with regard to the application and success of the
      transoral approach to airway surgery. We believe that further advances in device
      technology and a new generation of robotic equipment will facilitate the
      incorporation of surgical robotics in the advancement of minimally invasive
      endoscopic airway surgery.

PMID- 17224524
TI  - Bone-anchored hearing aids in infants and children younger than 5 years.
AB  - OBJECTIVE: While bone-anchored hearing aids (BAHAs) are currently indicated for
      rehabilitation in children older than 5 years with bilateral maximal conductive
      hearing loss, our objective was to capitalize on potentially important stages of
      auditory and speech-language development by providing BAHAs to children younger
      than 5 years. DESIGN: A retrospective review of surgical data of children
      receiving BAHA implants over a 10-year period. SETTING: The Hospital for Sick
      Children, Toronto, Ontario. PATIENTS: Twenty children 5 years or younger (mean +/
      SD age, 3.21 +/- 1.65 years) served as the study group, while 20 older children
      (mean +/- SD age, 7.63 +/- 1.55 years) served as the comparison group.
      INTERVENTIONS: All patients received BAHA implants. Children with cortical bone
      thickness less than 2.5 mm underwent a 2-stage procedure; children with cortical
      bone thickness greater than 4 mm underwent a single-stage procedure. MAIN OUTCOME
      MEASURES: Traumatic and skin revision complication rates and implantation
      interstage intervals were compared between groups. RESULTS: The mean +/- SD
      interstage interval was 7.72 +/- 3.81 months for the younger children, which was
      significantly longer than for the older children (4.41 +/- 2.51 months) (P<.003).
      Two traumatic fixture losses occurred in the younger children, while 4 occurred
      in the older children. Skin site revision was required in 3 younger children. All
      children are currently wearing their BAHAs. CONCLUSION: Two-stage BAHA
      implantation with a prolonged interval between stages yields surgical success in
      younger children comparable to that routinely observed in older children.

PMID- 17224525
TI  - Assessing impairment and disability of facial paralysis in patients with
      vestibular schwannoma.
AB  - OBJECTIVE: To evaluate facial impairment and disability with respect to quality
      of life in patients with facial paresis after vestibular schwannoma surgery.
      DESIGN: Cross-sectional observational study. SETTING: Academic, tertiary care
      hospital. PATIENTS: All consecutive patients during a 5-year period who underwent
      vestibular schwannoma surgery. MAIN OUTCOME MEASURES: The validated, patient
      graded Facial Clinimetric Evaluation (FaCE) scale questionnaire was administered
      to all study patients. Main outcome measures included total and social function
      FaCE scores. Subgroup analysis was performed on patient factors (age and sex),
      surgical factors (tumor size and time since operation), and House-Brackmann
      grade. RESULTS: A total of 56 FaCE questionnaires were returned (85% response
      rate): 28 patients (50%) had normal facial function (House-Brackmann grade I),
      and 28 patients (50%) had abnormal facial function (House-Brackmann grades II
      VI). There were no demographic differences between the normal and abnormal
      groups. The normal group had a total FaCE score of 96.2 compared with 67.1 in the
      abnormal group (P<.05). Subgroup analysis of patients with facial paresis
      revealed that age, sex, time since operation, tumor size, and House-Brackmann
      grade were not statistically significant factors predicting the FaCE social
      function score (P<.05). CONCLUSIONS: Facial paresis is an important complication
      of vestibular schwannoma surgery and will impair a patient's quality of life. The
      level of impairment may not be predicted by a patient's age, sex, tumor size,
      time since operation, or severity of facial paresis.

PMID- 17224527
TI  - Preauricular sinus: clinical course and associations.
AB  - OBJECTIVES: To evaluate the clinical course of congenital preauricular sinus
      (PAS) up until adulthood and to determine its association with congenital ear and
      renal abnormalities. DESIGN: Cohort survey. SETTING: Medical screening facility
      at a military base. PARTICIPANTS: All individuals in a cohort of male subjects
      who were medically assessed for conscription into the army between September 1,
      2003, and March 31, 2004. INTERVENTIONS: Subjects identified as having PAS were
      further evaluated with pure-tone audiometry and renal ultrasonography. MAIN
      OUTCOME MEASURES: Presence of PAS and associated hearing and renal abnormalities.
      RESULTS: Of 10 734 male subjects (median age, 19 years; range, 16-26 years)
      screened, 121 (1.13%) were found to have PAS, all of which were isolated. The
      point prevalence of PAS in Chinese, Malay, and Indian subjects was 1.36%, 0.69%,
      and 0.17%, respectively. Of the 29 subjects (24.0%) who developed symptoms
      (mainly sinus discharge), most had recurrent symptoms, and 7 (24.1%) of the 29
      had onset of symptoms after age 16 years. Only 1.7% and 2.6% of the subjects had
      associated hearing loss (sensorineural) and renal deformity (minor in nature),
      respectively. CONCLUSIONS: In a study of young adult males with PAS, associations
      with ear and renal abnormalities were found to be rare, although PAS had widely
      been acknowledged to be associated with these congenital defects. Up until
      adulthood, about one quarter of all lesions became symptomatic. Of those who
      developed symptoms, almost one third did so after age 16 years. The most common
      symptom was sinus discharge, which tended to be recurrent.

PMID- 17224526
TI  - Lymphocyte-white blood cell count ratio: a quickly available screening tool to
      differentiate acute purulent tonsillitis from glandular fever.
AB  - OBJECTIVE: To find a quickly available screening tool for the differentiation of
      patients with glandular fever from those with acute purulent tonsillitis. The
      null hypothesis was that there was no difference between the lymphocyte-white
      blood cell count (L/WCC) ratio between the 2 patient groups. DESIGN:
      Retrospective pilot study based on laboratory tests for lymphocyte counts, white
      blood cell counts, and the mononucleosis spot test. SETTING: Ear, Nose, and
      Throat Department, St George's Hospital, London, England. PATIENTS: One hundred
      twenty patients with glandular fever and 100 patients with bacterial tonsillitis.
      MAIN OUTCOME MEASURES: Results from the mononucleosis spot test in conjunction
      with the clinical picture and the L/WCC ratio were analyzed. Significant
      differences were evaluated using the Mann-Whitney test and Fisher exact test.
      RESULTS: The L/WCC ratio was significantly different in the 2 groups (P<.001).
      The mean L/WCC ratio in the glandular fever group was 0.54 and the mean L/WCC
      ratio in the bacterial tonsillitis group was 0.10. A ratio higher than 0.35 had a
      specificity of 100% and a sensitivity of 90% for the detection of glandular
      fever. CONCLUSIONS: We recommend that the L/WCC ratio should be used as an
      indicator to decide whether mononucleosis spot tests should be requested. A ratio
      higher than 0.35 had a high specificity in our study group.

PMID- 17224528
TI  - Factors associated with noncompliance to treatment with positive airway pressure.
AB  - OBJECTIVE: To identify risk factors that may predispose patients with a diagnosis
      of obstructive sleep apnea (OSA) to fail treatment with positive airway pressure
      (PAP) owing to noncompliance. DESIGN: Retrospective medical chart review.
      SETTING: Academic tertiary care center. PATIENTS: Patients who underwent
      polysomnography during 2 periods: from March 1999 to July 2001 and from March
      2003 to December 2003. MAIN OUTCOME MEASURES: Of the 949 patients identified,
      only 131 patients had complete medical and follow-up records that were adequate
      for analysis of compliance. Compliance was defined as using PAP for at least 4
      hours per night on 70% of the nights monitored. We used chi(2) and logistic
      regression analyses to assess correlations among PAP compliance and various
      patient variables as well as among sleep and titration study parameters. RESULTS:
      Of the 131 patients analyzed, 48 patients (37%) were noncompliant with PAP
      therapy. A statistically significant correlation was found between a low apnea
      hypopnea index (AHI) and PAP noncompliance (P = .004). CONCLUSIONS: In this
      study, a low AHI was identified as a risk factor for noncompliance with PAP
      treatment. Therefore, patients with OSA and with a low AHI may warrant closer
      follow-up to allow early identification of PAP treatment failure owing to
      noncompliance and to allow timely institution of other treatment modalities, such
      as surgery.

PMID- 17224529
TI  - Inheritance of Meniere's disease in the Finnish population.
AB  - OBJECTIVE: To study the inheritance of Meniere's disease in the Finnish
      population. DESIGN: A detailed questionnaire was sent to patients with symptoms
      resembling Meniere's disease previously examined at the Department of
      Otorhinolaryngology, Helsinki University Central Hospital, Finland. PATIENTS: The
      study population comprised 118 patients with symptoms resembling Meniere's
      disease. The patients were divided into groups based on the diagnostic criteria
      by the Committee on Hearing and Equilibrium of the American Academy of
      Otolaryngology-Head and Neck Surgery. MAIN OUTCOME MEASURES: Relatives with
      Meniere's disease, geographic distribution of birthplaces of grandparents,
      symptoms, vestibular findings, and audiologic and otoneurologic tests. RESULTS:
      Approximately 15% of the patients with definite Meniere's disease were found to
      represent familial disease. The majority of these patients were female, and they
      had more severe and intense attacks compared with patients with sporadic
      Meniere's disease. The mode of inheritance is autosomal dominant with incomplete
      penetrance. CONCLUSIONS: A significant part of Meniere's disease is inherited.
      The use of genetic isolates in which genetic homogeneity can be assumed might
      lead to the identification of gene defects leading to Meniere's disease.

PMID- 17224530
TI  - Epithelial shedding of the inferior turbinate in perennial allergic and
      nonallergic rhinitis: a riddle to solve.
AB  - OBJECTIVE: To examine the epithelial integrity of the inferior turbinate in
      patients with perennial allergic rhinitis (PAR) and perennial nonallergic
      (vasomotor) rhinitis (PNAR). DESIGN: Nonrandomized, controlled morphometric
      study. SETTING: University-affiliated hospital. PATIENTS: Fifty-eight inferior
      turbinate samples were processed for histological study. Nineteen were from
      patients with PAR, and 20 were from patients with PNAR. Samples from 19 healthy
      individuals who underwent rhinoplasty for cosmetic reasons served as control
      specimens. MAIN OUTCOME MEASURES: The length of the basement membrane (BM)
      covered with intact epithelium, covered with a single layer of basal cells, and
      devoid of epithelium was measured. RESULTS: Intact respiratory epithelium and
      areas of partial and complete epithelial denudation were encountered in control
      specimens and in samples from patients with PAR and PNAR. A significant
      difference was found between the 3 groups (P = .001). The proportion of the BM
      covered with undamaged epithelium was significantly greater in control specimens
      and in samples from patients with PNAR than in samples from patients with PAR;
      the difference between the former 2 groups was nonsignificant. Most of the
      epithelial damage in patients with PAR occurred between columnar and basal cells
      rather than between basal cells and the BM (P = .02). CONCLUSIONS: Epithelial
      shedding of the inferior turbinate is a genuine feature of PAR and is not an
      artifact of tissue sampling. The finding of greater epithelial exfoliation
      between basal cells and the more superficial columnar cells than between basal
      cells and the BM probably reflects different attachment qualities of these cells.

PMID- 17224531
TI  - Pyoderma gangrenosum in the head and neck.

PMID- 17224532
TI  - Kimura disease of the parotid and retroauricular region: a case report.

PMID- 17224533
TI  - Radiology quiz case 1. Cystic fibrosis.

PMID- 17224534
TI  - Radiology quiz case 2. Blindness secondary to nasal polyposis.

PMID- 17224535
TI  - Pathology quiz case 1. Laryngeal myxoma.

PMID- 17224536
TI  - Pathology quiz case 2. Solitary neurofibroma (SNF) of the parapharyngeal space.

PMID- 17224537
TI  - Progressive extragenital lichen sclerosus successfully treated with narrowband UV
      B phototherapy.

PMID- 17224539
TI  - Effect of health care delivery models on melanoma thickness and stage in a
      university-based referral center: an observational pilot study.
AB  - OBJECTIVE: To compare the effect of differing health care delivery models,
      specifically, gatekeeper (GK) vs direct access (DA) routes, on melanoma outcome
      as measured by tumor thickness and cancer stage at diagnosis. DESIGN:
      Retrospective medical record review of patients previously diagnosed as having
      cutaneous melanoma who were referred to a university-based clinic from January 1,
      1996, through December 31, 2000. SETTING: Stanford Pigmented Lesion and Cutaneous
      Melanoma Clinic, Stanford, Calif. Patients Two hundred thirty-four patients with
      primary melanoma stratified according to health care access route (GK or DA).
      MAIN OUTCOME MEASURES: Differences in Breslow thickness, American Joint Committee
      on Cancer stage, histologic features, patient delay in seeking medical attention,
      and physician delay in diagnosis (time between initial physician visit and
      diagnostic biopsy procedure). RESULTS: Of 234 patients, 168 (72%) were referred
      through the DA route and 66 (28%) through the GK route. A significant association
      was found between physician delay and access route; patients in the DA group
      underwent biopsy sooner (< or =3 months vs >3 months) than those in the GK group
      (P<.001). No significant difference was observed in stage at diagnosis
      (predominantly stage IA), proportion of nodular melanoma (DA 4% vs GK 2%),
      patient delay, or median tumor thickness between DA and GK routes (0.42 mm vs
      0.50 mm, respectively). A trend toward a greater proportion of histologically
      ulcerated melanoma was observed in the DA group compared with the GK group (12%
      vs 5%, respectively; P = .06). CONCLUSIONS: This pilot study demonstrated no
      difference in outcome between GK and DA routes as measured by melanoma thickness
      and stage, although patients in the DA group underwent diagnostic biopsy sooner
      than those in the GK group. The potential effect of health care models on
      melanoma outcomes merits further study.

PMID- 17224538
TI  - Visual screening for malignant melanoma: a cost-effectiveness analysis.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of various melanoma screening
      strategies proposed in the United States. DESIGN: We developed a computer
      simulation Markov model to evaluate alternative melanoma screening strategies.
      PARTICIPANTS: Hypothetical cohort of the general population and siblings of
      patients with melanoma. Intervention We considered the following 4 strategies:
      background screening only, and screening 1 time, every 2 years, and annually, all
      beginning at age 50 years. Prevalence, incidence, and mortality data were taken
      from the Surveillance, Epidemiology, and End Results Program. Sibling risk,
      recurrence rates, and treatment costs were taken from the literature. MAIN
      OUTCOME MEASURES: Outcomes included life expectancy, quality-adjusted life
      expectancy, and lifetime costs. Cost-effectiveness ratios were in dollars per
      quality-adjusted life year (US dollars/QALY) gained. RESULTS: In the general
      population, screening 1 time, every 2 years, and annually saved 1.6, 4.4, and 5.2
      QALYs per 1000 persons screened, with incremental cost-effectiveness ratios of US
      dollars 10,100/QALY, US dollars 80,700/QALY, and US dollars 586,800/QALY,
      respectively. In siblings of patients with melanoma (relative risk, 2.24 compared
      with the general population), 1-time, every-2-years, and annual screenings saved
      3.6, 9.8, and 11.4 QALYs per 1000 persons screened, with incremental cost
      effectiveness ratios of US dollars 4000/QALY, US dollars 35,500/QALY, and US
      dollars 257,800/QALY, respectively. In higher risk siblings of patients with
      melanoma (relative risk, 5.56), screening was more cost-effective. Results were
      most sensitive to screening cost, melanoma progression rate, and specificity of
      visual screening. CONCLUSIONS: One-time melanoma screening of the general
      population older than 50 years is very cost-effective compared with other cancer
      screening programs in the United States. Screening every 2 years in siblings of
      patients with melanoma is also cost-effective.

PMID- 17224540
TI  - Efficacy of a partner assistance intervention designed to increase skin self
      examination performance.
AB  - OBJECTIVE: To examine the role of partner assistance in learning and
      implementation of an intervention designed to promote skin self-examination (SSE)
      behaviors in persons at risk of developing melanoma. DESIGN: Randomized
      controlled trial with immediate and 4-month follow-up visits. SETTING: Clinical
      offices in the ambulatory care area of a hospital. Patients The study included
      130 participants and their cohabiting partners drawn from a melanoma registry.
      Intervention The subjects were randomly assigned to receive the intervention
      either as solo learning or as dyadic learning. The intervention consisted of a 10
      minute demonstration of the ABCDE (asymmetry of shape, border irregularity, color
      variegation, diameter > or =6 mm, and evolution of the lesion) rule and skills
      training. MAIN OUTCOME MEASURES: Behavioral measures included self-reported
      performance of SSE and use of a body map designed to record areas of concern
      found during SSE. Intentions, along with attitudinal measures such as perceived
      importance of SSE and self-efficacy in performing SSE, were also assessed at the
      4-month follow-up visit. RESULTS: The participants in the dyadic learning group
      were significantly more likely to report engaging in SSE behaviors (P<.05). The
      dyadic learning group also exhibited greater intentions to perform future SSE
      (P<.01), higher perceived importance of SSE (P<.01), and higher perceived self
      efficacy (P<.01). CONCLUSION: Dyadic learning may be more effective than solo
      learning in regard to interventions designed to teach and promote health
      behaviors, such as SSE.

PMID- 17224541
TI  - Second lymphomas and other malignant neoplasms in patients with mycosis fungoides
      and Sezary syndrome: evidence from population-based and clinical cohorts.
AB  - OBJECTIVE: To assess risks for developing second malignancies in patients with
      mycosis fungoides or Sezary syndrome. DESIGN: Retrospective study of 2 cohorts.
      SETTING: Nine population-based US cancer registries that constitute the
      Surveillance, Epidemiology, and End Results Program (SEER-9), and Stanford
      University referral center cohort of patients with cutaneous lymphoma. Patients
      with mycosis fungoides or Sezary syndrome from the SEER-9 registry diagnosed and
      followed up from 1984 through 2001 and from the Stanford University cohort
      diagnosed and followed up from 1973 through 2001. MAIN OUTCOME MEASURES: Relative
      risk was estimated using the standardized incidence ratio (SIR). The expected
      cancer incidence for both cohorts was calculated using age-, sex-, race-, and
      calendar year-specific SEER-9 incidence rates for the general population.
      Nonmelanoma skin cancers were excluded because these cancers are not routinely
      reported by the SEER database. RESULTS: In the SEER-9 cohort (n = 1798), there
      were 197 second instances of cancer (SIR = 1.32; 95% confidence interval [CI],
      1.15-1.52) at all sites. Significantly elevated risk (P<.01) was observed for
      Hodgkin disease (6 cases; SIR = 17.14; 95% CI, 6.25-37.26) and non-Hodgkin
      lymphoma (27 cases; SIR = 5.08; 95% CI, 3.34-7.38). Elevated risk (P<.05) was
      also observed for melanoma (10 cases; SIR = 2.60; 95% CI, 1.25-4.79), and urinary
      cancer (21 cases; SIR = 1.74; 95% CI, 1.08-2.66). In the Stanford University
      cohort (n = 429), there were 37 second instances of cancer (SIR = 1.04; 95% CI,
      0.76-1.44). Elevated risk (P<.01) was observed for Hodgkin disease (3 cases; SIR
      = 27.27; 95% CI, 5.35-77.54). Elevated risk (P<.05) was also observed for biliary
      cancer (2 cases; SIR = 11.76; 95% CI, 1.51-42.02). CONCLUSION: Updated SEER
      (population based) and Stanford (clinic based) data confirm the generalizability
      of earlier findings of increased risk of lymphoma in patients with mycosis
      fungoides or Sezary syndrome.

PMID- 17224542
TI  - Lymphomatoid keratosis: an epidermotropic type of cutaneous lymphoid hyperplasia:
      clinicopathological, immunohistochemical, and molecular biological study of 6
      cases.
AB  - OBJECTIVE: To provide evidence that lymphomatoid keratosis should be categorized
      as an epidermotropic subtype of cutaneous lymphoid hyperplasia. DESIGN:
      Clinicopathological, immunohistochemical, and molecular biological studies of
      epidermotropic and dermal bandlike infiltrates of lymphocytes without necrotic
      keratinocytes, Civatte bodies, or Max-Joseph spaces and solar lentigo or
      seborrheic keratosis adjacent to the lesion, but with epidermal hyperplastic
      change (clinically scaly plaque) in cases of lymphomatoid keratosis. Conventional
      histopathologic study as well as immunohistochemical examinations for CD1a, CD3,
      CD4, CD8, CD20, and CD79a and S100 protein and genotypic examinations were
      performed. SETTING: University departments comprising 2 sections of dermatology
      and 1 section of pathology. MAIN OUTCOME MEASURES: Ratio of T to B cells and of
      CD4(+) to CD8(+) cells, and the phenotype of epidermotropic cells were evaluated.
      Gene rearrangement of the immunoglobulin heavy chain gene and T-cell receptor
      (TCR)-beta and TCRgamma genes was also investigated by the polymerase chain
      reaction method. RESULTS: Immunohistochemically, epidermotropic CD20(+) and/or
      CD79a(+) cells were present. In the upper dermal lymphocytic infiltrates, the
      CD3(+)/CD79a(+) cell ratio ranged from 5:5 to 8:2. The CD4(+)/CD8(+) cell ratio
      was within normal limits. Rearrangements of the TCRgamma gene were demonstrated
      in 2 cases and of the TCRbeta gene in 1 case. CONCLUSIONS: Our results indicate
      that lymphomatoid keratosis is a clinically benign keratotic lesion but
      histologically malignant, simulating mycosis fungoides. Immunohistochemical
      findings showed a reaction pattern in all cases, but genotypical examination
      showed some clonal dermatoses. Therefore, "lymphomatoid" keratosis should be
      classed as a pseudolymphoma, namely, a subtype of cutaneous lymphoid hyperplasia
      with epidermotropism.

PMID- 17224543
TI  - Growth inhibition of Trichophyton species by Pseudomonas aeruginosa.
AB  - OBJECTIVE: To assess the ability of Pseudomonas aeruginosa to inhibit the growth
      of Trichophyton mentagrophytes (TM) and Trichophyton rubrum (TR). DESIGN:
      Pseudomonas aeruginosa, Escherichia coli, or Staphylococcus epidermidis were
      grown in co-culture with either TM or TR. SETTING: An academic medical center.
      MAIN OUTCOME MEASURES: The total fungal units and hyphal-spore ratio were
      measured at days 1, 5, 10, and 15. RESULTS: There was a 73% and 46% reduction of
      total fungal units and a final hyphal-spore ratio of 0.16 and 0.04, respectively,
      when TM and TR were co-cultured with P aeruginosa. The number of fungal units
      increased when TM and TR were cultured with E coli (28% and 42%, respectively), S
      epidermidis (13% and 18%, respectively), and control media (44% and 62%,
      respectively), and the hyphal-spore ratio increased to above 30 in the presence
      of S epidermidis, E coli, and control media. CONCLUSION: Pseudomonas aeruginosa
      exhibits growth inhibitory properties against TM and TR.

PMID- 17224544
TI  - Intertriginous eruption associated with chemotherapy in pediatric patients.
AB  - BACKGROUND: Cutaneous eruptions commonly occur in children receiving
      chemotherapy, and the clinical situation often demands immediate diagnosis and
      initiation of treatment. Several patterns of cutaneous eruptions to chemotherapy
      have been reported; however, the nomenclature used to describe these entities has
      been derived from the histologic findings. The morphologic characteristics,
      distribution, and natural history of these reactions have not been well
      established. OBSERVATIONS: We report the clinical features of 16 pediatric
      patients with a distinctive chemotherapy-induced eruption. The eruption is most
      prominent in or limited to intertriginous regions and areas of occlusion. We were
      not able to identify any single chemotherapeutic agent or even a group of agents
      in the same pharmacologic family that seemed to be associated with this reaction.
      The eruption did not appear to be related to sex, age, ethnicity, underlying
      malignancy, or genetic disease. CONCLUSIONS: Recognition of this distinct
      clinical pattern can help rule out more serious entities, avoid a biopsy, and
      reassure the physician and patient of the benign and self-resolving clinical
      course. This entity may be observed with many chemotherapeutic agents and
      underlying diseases, but most often with high-dose chemotherapy protocols.

PMID- 17224545
TI  - The head-tilt maneuver: a clinical aid in recognizing head and neck
      angiosarcomas.
AB  - BACKGROUND: Cutaneous angiosarcoma is a rare, life-threatening tumor that is
      often initially misdiagnosed. This delay in diagnosis can affect tumor growth,
      metastatic potential, and prognosis. OBSERVATIONS: We describe the "head-tilt
      maneuver," which highlights the vascular nature of these lesions and can be of
      potential benefit in early recognition and better appreciation of the clinical
      extent of this tumor. CONCLUSION: Early recognition and aggressive management of
      these tumors can afford the best opportunity for cure.

PMID- 17224546
TI  - Trimethylaminuria (fish-odor syndrome): a case report.
AB  - BACKGROUND: Trimethylaminuria (fish-odor syndrome) is a rare metabolic disorder
      characterized by a body malodor similar to that of decaying fish. The condition
      results from mutations affecting the flavin-containing monooxygenase 3 (FMO3)
      gene. Affected individuals may exhibit a variety of psychosocial phenomena. A
      high index of suspicion for this disorder needs to be maintained when treating
      individuals presenting with a history of real or perceived body odor. Observation
      We evaluated a 41-year-old man who presented with a long medical history of a
      fishy body odor. Results from biochemical investigations confirmed a diagnosis of
      primary trimethylaminuria, and results of molecular genetic studies revealed
      homozygosity for a mutation on exon 4 of the FMO3 gene, FMO3/P153L (c.458C -->
      T). The patient found that information he subsequently obtained about his
      condition on the Internet and discussion with friends and family members to be
      the most useful therapeutic approach. CONCLUSIONS: Trimethylaminuria is a rare
      metabolic disorder. Psychological accompaniments are recognized as major sources
      of distress to affected individuals. We discuss the features of this syndrome and
      highlight the importance of counseling and support in the treatment of such
      patients.

PMID- 17224547
TI  - Relapsing polychondritis and malignant lymphoma: is polychondritis
      paraneoplastic?
AB  - BACKGROUND: Relapsing polychondritis (RP) is associated with other rheumatic or
      autoimmune disease in about 30% of cases; however, an association with malignancy
      is rare with the exception of myelodysplastic syndrome (MDS). Observation Herein
      we report the first case, to our knowledge, of RP following splenic non-Hodgkin
      lymphoma (NHL), and we have reviewed all the previous well-documented reports
      that described the cases of RP associated with malignant lymphoma (ML).
      CONCLUSIONS: Our case and the review of reported cases showed that RP preceded ML
      in 2 cases, RP occurred after diagnosis and treatment of ML in 2 cases, and RP
      and ML occurred simultaneously in 1 case. The types of ML encountered were
      Hodgkin lymphoma, orbital mucosa associated lymphoid tissue type lymphoma, nodal
      NHL, and splenic NHL. From the frequent association of RP with MDS and, less
      frequently, with ML, we speculate that some RP cases may occur as a
      paraneoplastic condition of the concurrent hematological malignancies.

PMID- 17224548
TI  - Short-term thallium intoxication: dermatological findings correlated with
      thallium concentration.
AB  - BACKGROUND: The dermatological features and skin biopsy findings of short-term
      thallium intoxication have been described. However, the correlation between the
      dermatological findings and the thallium concentration, the prognosis of
      peripheral neuropathy, and a cutaneous nerve biopsy study are lacking.
      OBSERVATIONS: Two patients initially developed perioral numbness, erythematous
      facial rashes, and polyneuropathy after ingesting thallium-containing water.
      Severe diffuse alopecia was noted, and a skin biopsy specimen revealed
      parakeratosis and vacuolar degeneration of the basal layer. Examinations of the
      hair mount demonstrated a tapered appearance of the anagen root. A serial
      cutaneous nerve biopsy study showed a loss of epidermal nerves 7 weeks and even 1
      year after the thallium intoxication. A toxicology survey disclosed a high
      concentration of thallium (about 3124 mg/L) in the water. The clinical
      dermatological features subsided completely, but polyneuropathy with severe
      painful feet persisted. The blood and daily urinary thallium concentrations
      decreased slowly in the following 3-month period. CONCLUSIONS: The clinical
      dermatological features subsided completely, but painful polyneuropathy
      persisted. The series cutaneous nerve biopsy specimens showed persistent damage
      to the sensory nerve endings. The disappearance of the dermatological features
      and the appearance of Mees lines correlated with the decrease of blood and
      urinary thallium concentrations.

PMID- 17224549
TI  - Melanoma screening: focusing the public health journey.

PMID- 17224550
TI  - Skin microecology: the old and the new.

PMID- 17224551
TI  - Dermal plaques of the face and scalp. Platelike osteoma cutis.

PMID- 17224552
TI  - Erythematous atrophic macules and papules following the lines of Blaschko. Focal
      dermal hypoplasia (FDH), or Goltz syndrome.

PMID- 17224553
TI  - Atrophic macules and soft papules in a 24-year-old woman. Anetoderma associated
      with antiphospholipid antibodies.

PMID- 17224554
TI  - Multiple plaques on the hands and feet. Mycosis fungoides (MF) palmaris et
      plantaris (MFPP).

PMID- 17224555
TI  - Prevalence of skin diseases and cutaneous manifestations among Iranian children:
      a survey of 1417 children.

PMID- 17224556
TI  - Hair graying in substance addiction.

PMID- 17224557
TI  - Ambiguous igneous rocks.

PMID- 17224558
TI  - Effect of tacrolimus on vitiligo in absence of UV radiation exposure.

PMID- 17224559
TI  - Awareness of generational differences is the first step.

PMID- 17224560
TI  - Acute digital gangrene in a newborn.

PMID- 17224561
TI  - Lichen spinulosus: excellent response to tretinoin gel and hydroactive adhesive
      applications.

PMID- 17224562
TI  - Dermoscopic diagnosis of furuncular myiasis.

PMID- 17224563
TI  - Spontaneous Citrobacter freundii infection in an immunocompetent patient.

PMID- 17224564
TI  - Bosentan as a rescue therapy in scleroderma refractory digital ulcers.

PMID- 17224565
TI  - Reflectance-mode confocal microscopy for the diagnosis of sebaceous hyperplasia
      in vivo.

PMID- 17224566
TI  - Muscle biopsy in patients with myalgia: still a painful decision.

PMID- 17224567
TI  - Improving the appropriateness of carotid endarterectomy.

PMID- 17224568
TI  - Patterns of sensory abnormality in cortical stroke: evidence for a dichotomized
      sensory system.
AB  - OBJECTIVE: To characterize sensory symptoms in patients with stroke occurring in
      the cerebral cortex. METHODS: We studied clinical and imaging findings of 24
      patients who had prominent sensory symptoms without definitive motor dysfunction.
      RESULTS: According to the sensory manifestations, patients were divided into
      dominant impairment of primitive sensation (DIPS) group, dominant impairment of
      cortical sensation (DICS) group, and paresthesia-only group. DIPS was related to
      lesions involving the parietal operculum and the insular cortex, whereas DICS was
      related to the lesions affecting the postcentral gyrus. Patients with paresthesia
      only had smaller lesions located in the postcentral gyrus. DIPS group patients
      were more often women (p = 0.013), more often had dysarthria (n = 0.043), and
      more often developed central poststroke pain or paresthesia (n = 0.005) than the
      DICS group patients. Restricted sensory changes are common, predominantly
      involving the perioral or finger areas. CONCLUSIONS: Sensory patterns in these
      patients are generally consistent with the dichotomized (SI and SII) sensory
      system in the cerebral cortex. Involvement of insular and opercular areas is
      related to primitive sensory impairment and development of central poststroke
      pain, whereas postcentral gyrus involvement is related to cortical sensory loss
      without poststroke pain. The pattern of restricted sensory changes is generally
      consistent with the Penfield sensory topography.

PMID- 17224569
TI  - Acute reversible cerebellar lesions associated with metronidazole therapy.

PMID- 17224570
TI  - The role of muscle biopsy in investigating isolated muscle pain.
AB  - OBJECTIVE: To evaluate the muscle biopsy findings from 240 patients who had
      isolated muscle pain. METHODS: Histopathology, immunohistochemistry for
      dystrophin, dystrophin-related proteins, major histocompatibility complex type I,
      and biochemical analysis of glycolytic and mitochondrial respiratory chain
      enzymes were performed on muscle biopsies. An attempt was made to correlate
      pathologic data and clinical findings (sex, age, quality and distribution of
      symptoms, serum CK levels, and EMG recording). RESULTS: We have described five
      groups of patients based on muscle biopsy findings: 51.6% had heterogeneous
      myopathic abnormalities; only 19% of them had a specific myopathic picture, i.e.,
      central nuclei myopathy, central core disease, myopathy with tubular aggregates
      or with trabecular fibers or abnormalities of fiber typing; 20% had signs of
      respiratory chain dysfunction but only one patient had a probable mitochondrial
      disease; 7% had a neurogenic pattern; 2.4% had a metabolic myopathy
      (phosphorylase or phosphofructokinase deficiency); and 19% had normal muscle
      biopsy. No clear-cut correlation between muscle biopsy and clinical data was
      observed except for those patients with a metabolic myopathy. CONCLUSIONS: The
      probability that a patient complaining only of muscle pain and with a normal
      neurologic examination has a definite muscle pathology is 2%. Only patients with
      sole exercise-related muscle pain and sCK seven times higher than the normal
      value are strongly suspected of having a metabolic myopathy. A rigorous selection
      of patients is needed before performing a muscle biopsy.

PMID- 17224571
TI  - Has evidence changed practice?: appropriateness of carotid endarterectomy after
      the clinical trials.
AB  - OBJECTIVE: To assess how appropriateness of and indications for carotid
      endarterectomy (CEA) have changed following the publication of several large
      international randomized controlled trials (RCTs) designed to rationalize use of
      CEA. METHODS: The New York Carotid Artery Surgery Study (NYCAS) is a population
      based cohort study of all CEAs performed on elderly patients from January 1998
      through June 1999 in New York State. Detailed clinical data were abstracted from
      medical charts to assess indications for and appropriateness of surgery using a
      list of 1,557 indications for CEA developed by national experts using RAND
      appropriateness methods. Deaths and strokes within 30 days of surgery were
      ascertained and confirmed by two physicians. RESULTS: Among the 9,588 patients,
      the mean age was 74.6 years and 93.6% had 70 to 99% carotid stenosis. Nearly
      three-quarters of patients (72.3%) underwent CEA for asymptomatic stenosis, 18.6%
      for TIA, and 9.1% for stroke. Overall, 87.1% of operations were done for
      appropriate reasons, 4.3% for uncertain reasons, and 8.6% for inappropriate
      reasons (vs 32% inappropriate before the RCTs, p < 0.0001). Among procedures
      judged inappropriate, the most common reasons were high comorbidity in
      asymptomatic patients (62.2%), operating after a major stroke (14.2%), or for
      minimal stenosis (10.5%). Among asymptomatic patients, those with high
      comorbidity had over twice the risk of death or stroke compared to those without
      high comorbidity (7.13% vs 2.69%, p < 0.0001). CONCLUSIONS: Since publication of
      the randomized controlled trials, there has been a reduction in the proportion of
      patients undergoing carotid endarterectomy (CEA) for inappropriate reasons. The
      shift toward many asymptomatic patients undergoing CEA is concerning because the
      net benefit from surgery for these patients is low and is reduced further for
      patients with high comorbidity.

PMID- 17224572
TI  - Mortality from combined carotid endarterectomy and coronary artery bypass surgery
      in the US.
AB  - We determined hospital mortality and postoperative stroke rates after combined
      carotid endarterectomy (CEA) and coronary artery bypass graft surgery (CABG) vs
      CABG alone, using the US Nationwide Inpatient Sample. CEA-CABG combined was
      1.06%. After correcting for comorbidities, the odds ratio for postoperative
      stroke or death for CEA-CABG was 1.38 (95% CI 1.27 to 1.50) vs CABG. With the
      increase in postoperative stroke and death, a randomized, controlled clinical
      trial of combined CEA-CABG is indicated.

PMID- 17224573
TI  - Outcome of noninvasive ventilation in children with neuromuscular disease.
AB  - OBJECTIVE: To assess the effect of institution of noninvasive ventilation (NIV)
      on clinical outcome and quality of life (QOL) in a cohort of children with severe
      neuromuscular disorders. METHODS: We reviewed records and obtained clinical data
      from the year prior to commencing NIV and annually thereafter. Data obtained
      included diagnosis, patient symptoms, mortality, NIV adverse effects, pulmonary
      function tests, polysomnographic data, length of hospitalizations, and health
      care costs. Patients and parents completed questionnaires assessing QOL with NIV
      and recalling QOL before NIV. RESULTS: Fourteen of 17 (82%) suitable patients
      were enrolled. Follow-up ranged from 6 to 84 months (median 30). Symptoms of
      daytime sleepiness (p = 0.003) and headache (p = 0.046) improved after initiation
      of NIV. Sleep quality assessed by polysomnography also improved. Hospitalization
      rates (p = 0.002) and health care costs (p = 0.003) decreased. QOL remained
      stable after NIV, despite disease progression. CONCLUSION: Treatment of
      respiratory failure, in children with neuromuscular disease, with noninvasive
      ventilation results in a reduction in symptoms, hospitalizations, and health care
      costs without adverse effects on quality of life.

PMID- 17224574
TI  - Time frame and predictors of recovery from disability following recurrent
      ischemic stroke.
AB  - OBJECTIVE: To assess the rate, degree, and predictors of recovery from a disabled
      to nondisabled state in patients disabled after recurrent ischemic stroke.
      METHODS: Patients with ischemic stroke enrolled in the Management of
      Atherothrombosis with Clopidogrel in High Risk Patients (MATCH) Study underwent
      prospective assessment of their modified Rankin score (mRS) at 1, 3, 6, 12, and
      18 months after enrollment and after recurrent stroke. Patients disabled (defined
      as mRS > or = 3) after recurrence were analyzed for recovery (defined as mRS < 3)
      during the 18 months, and predictors of recovery were sought using a Cox
      proportional-hazard multiple regression analysis. RESULTS: Three hundred forty
      five (54%) of 637 patients were disabled after recurrent ischemic stroke; 115
      (33%) patients had been disabled and 230 (66%) nondisabled before stroke
      recurrence. At recurrence, the degree of disability was moderate (mRS 3) in 135
      (39%) patients, severe (mRS 4) in 139 (40%), and very severe (mRS 5) in 71 (21%).
      After 12 months' median follow-up, 117 (34%, 95% CI: 29 to 39%) had recovered: 68
      (50%, 42 to 59%) of 135 moderately disabled, 45 (32%, 25 to 41%) of 139 severely
      disabled, and 4 (6%, 2 to 14%) of 71 very severely disabled; 70 (20.3%) patients
      died. From recurrence, median time to recovery was 6 months (mRS 3) and 18 months
      (mRS 4); 94% with very severe disability had not recovered at 18 months.
      Independent predictors of recovery were moderate disability at recurrence (mRS 3)
      compared with severe (mRS 4: hazard ratio [HR] 1.5; 95% CI 1.04 to 2.3) or very
      severe disability (mRS 5: HR 7.6; 2.7 to 20) and a nondisabled vs disabled state
      before recurrence (HR 4.0; 2.3 to 6.8). CONCLUSIONS: The rate of recovery from
      recurrent ischemic stroke was greatest in the first 6 months; one-third of
      patients recovered within 12 months. The significant predictors of recovery were
      a nondisabled state before recurrence and increasing severity of the recurrent
      stroke.

PMID- 17224575
TI  - Differentiation of HAM/TSP from patients with multiple sclerosis infected with
      HTLV-I.
AB  - OBJECTIVE: To better differentiate patients with human T lymphotropic virus type
      I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) from
      patients with multiple sclerosis (MS) who are HTLV-I seropositive, we compared
      the HTLV-I antibodies and HTLV-I proviral DNA loads in CSF and peripheral blood
      mononuclear cells (PBMC). METHODS: Intrathecal synthesis of HTLV-I antibodies and
      HTLV-I proviral DNA loads in CSF and PBMC were measured and compared in 39
      Brazilian patients: 17 HAM/TSP and 22 HTLV-I-seropositive non-HAM/TSP (7 with
      other neurologic diseases, 11 asymptomatic carriers, and 4 HTLV-I-seropositive
      patients with an MS-like phenotype). In addition, we followed immunologic and
      virologic markers in comparison to the clinical course (by Kurtzke Expanded
      Disability Status Scale) of seven patients (five with HAM/TSP and two with an MS
      like phenotype) for a mean period of 16 (SD +/- 5) months. RESULTS: The proviral
      load in CSF and PBMC was higher in HAM/TSP than in non-HAM/TSP patients, except
      in the two HTLV-I-seropositive patients with an MS-like phenotype that also
      fulfilled the criteria for HAM/TSP. Higher HTLV-I proviral DNA load in CSF was
      associated with the higher proviral DNA load in PBMC and lower intrathecal
      synthesis of HTLV-I antibodies. These laboratory findings remained stable during
      follow-up. CONCLUSION: The high proviral load in peripheral blood mononuclear
      cells or in CSF or both may be a good marker of human T lymphotropic virus type I
      (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and can
      differentiate patients with HAM/TSP from patients with multiple sclerosis
      infected with HTLV-I.

PMID- 17224576
TI  - Progression of white matter hyperintensities in elderly individuals over 3 years.
AB  - OBJECTIVE: The aims of this study were to examine white matter hyperintensities
      (WMHs) in the brains of elderly individuals, the rate of progression, the
      anatomic regions most vulnerable, and the predictors of change. METHODS: We
      examined 51 healthy volunteers (mean age 71 years) with T2-weighted brain MRI on
      the same scanner 3 years apart. WMH volumes were determined by an automated
      method, and the anatomic location of change was determined for both deep WMHs
      (DWMHs) and periventricular WMHs (PVWMHs). RESULTS: The total brain WMH volume
      increased by 39.6%, i.e., 13.2% per year, with the change in DWMH being 43.8% and
      29.7% in PVWMH. The increase was significant in all regions except the occipital
      lobe and cerebellum. Age, sex, and cerebrovascular risk factors were not
      significant predictors of WMH progression. The main predictor of progression was
      baseline level of WMH. The number of WMH lesions increased by a mean of 1.78, and
      the progression was mainly accounted for by an increase in very large (>16 mm)
      lesions. Eight subjects showed a slight decrease in WMH. CONCLUSIONS: White
      matter hyperintensities are progressive in most elderly individuals with an
      increasing rate of progression as the burden of lesions increases. The rate of
      progression is greater in deep white matter and in the anterior brain regions.
      Risk factors for progression are not well understood, and genetic and other
      environmental factors must be examined. Quantitation of white matter
      hyperintensities may serve as a surrogate marker of the progression of small
      vessel disease.

PMID- 17224577
TI  - Ocular dipping and ping-pong gaze in hypoxic encephalopathy.

PMID- 17224578
TI  - Education and Alzheimer disease without dementia: support for the cognitive
      reserve hypothesis.
AB  - BACKGROUND: Individuals with no cognitive impairment during life but with
      neuropathologic Alzheimer disease (AD) may represent cases of presymptomatic, or
      unrecognized early symptomatic, AD. The cognitive reserve hypothesis suggests
      that at a particular level of AD pathology, highly educated individuals are less
      likely to manifest clinical symptoms of dementia vs less-educated individuals.
      OBJECTIVE: To investigate whether education can help explain a clinical diagnosis
      of no dementia within 1 year of death among individuals with neuropathologic
      diagnoses of AD. METHODS: Samples of participants (age 65+ years at last clinical
      assessment) meeting each of three neuropathologic criteria for AD were
      constructed using data from the National Alzheimer's Coordinating Center Minimum
      and Neuropathology Data Sets. Generalized linear mixed models (using the logit
      link function) were used in each sample to examine whether years of education was
      associated with dementia within 1 year of death, adjusting for other relevant
      variables. RESULTS: Twelve percent of individuals meeting Khachaturian
      (122/1,009), 19% meeting low, intermediate, or high likelihood for National
      Institute on Aging/Reagan Institute (320/1,704), and 14% meeting possible,
      probable, or definite Consortium to Establish a Registry for Alzheimer's Disease
      (265/1,835) neuropathologic criteria for AD were nondemented at their final
      clinical assessment. Persons with more education were less likely to have a
      dementia diagnosis in each sample. CONCLUSIONS: Regardless of the neuropathologic
      criteria used, education is predictive of dementia status among individuals with
      neuropathologic Alzheimer disease. These results support the theory that
      individuals with greater cognitive reserve, as reflected in years of education,
      are better able to cope with AD brain pathology without observable deficits in
      cognition.

PMID- 17224579
TI  - Fulminant idiopathic intracranial hypertension.
AB  - OBJECTIVE: To describe the incidence and characteristics of acute and rapidly
      progressive visual loss in idiopathic intracranial hypertension (IIH). METHODS:
      We reviewed the medical records of all patients with IIH seen at two
      institutions. "Fulminant IIH" was defined as the acute onset of symptoms and
      signs of intracranial hypertension (less than 4 weeks between onset of initial
      symptoms and severe visual loss), rapid worsening of visual loss over a few days,
      and normal brain MRI and MR venography (or CT venogram). RESULTS: Sixteen cases
      with "fulminant IIH" were included (16 women, mean age 23.8 years [range 14 to 39
      years]). All were obese. One patient had iron-deficiency anemia, four had
      systemic hypertension, and none had known sleep apnea syndrome. Acute or subacute
      headache, nausea and vomiting, and visual loss were present in all patients. The
      first lumbar puncture performed for the diagnosis showed a mean CSF opening
      pressure of 54.1 cm H(2)O (range 29 to 60 cm H(2)O). In addition to the initial
      lumbar puncture, medical treatment included acetazolamide (1 to 2 g/day) in all
      patients, and IV methylprednisolone in four patients. Repeat lumbar punctures
      were performed in 11 of the 16 patients. Surgical treatment (optic nerve sheath
      fenestration in five cases, lumboperitoneal CSF shunting procedure in nine cases,
      and ventriculoperitoneal shunting procedure in two cases) was performed because
      of ongoing visual loss in all cases. The median delay between evaluation in neuro
      ophthalmology and surgery was 3 days (range a few hours to 37 days). All patients
      reported dramatic improvement of headaches and vomiting following surgery. Visual
      function improved in 14 cases, although 8 patients (50%) remained legally blind.
      Visual fields remained severely altered in all cases. CONCLUSION: Severe and
      rapidly progressive visual loss suggests "fulminant idiopathic intracranial
      hypertension" and should prompt aggressive management. Urgent surgery may be
      required in these patients, and temporizing measures such as repeat lumbar
      punctures, lumbar drainage, and IV steroids considered.

PMID- 17224580
TI  - Sodium channels and pain.

PMID- 17224581
TI  - Posterior insular stroke causing selective loss of contralateral nonpainful
      thermal sensation.

PMID- 17224582
TI  - Nuclear imaging can predict pathologic diagnosis in progressive nonfluent
      aphasia.

PMID- 17224583
TI  - Homer 3 autoimmunity in subacute idiopathic cerebellar ataxia.

PMID- 17224584
TI  - Prospective study of symptomatic atherothrombotic intracranial stenoses: the
      GESICA study.

PMID- 17224585
TI  - Obesity and migraine: a population study.

PMID- 17224586
TI  - Elderly-onset essential tremor is associated with dementia.

PMID- 17224587
TI  - An almost missed leptomeningeal angioma in Sturge-Weber syndrome.

PMID- 17224588
TI  - Let's put the mouth back in the body.

PMID- 17224589
TI  - Thinking of med school? Where do you live?

PMID- 17224591
TI  - Decline in breast cancer since HRT study.

PMID- 17224592
TI  - New mental health services for deaf patients.

PMID- 17224593
TI  - Wasting emergency aid in Africa.

PMID- 17224594
TI  - The medical view from 34,000 feet.

PMID- 17224595
TI  - Those "in the know" should lay the parameters for human resource planning.

PMID- 17224596
TI  - A woman with recurrent cardiac ischemia without coronary artery disease.

PMID- 17224597
TI  - A woman with orbital myositis.

PMID- 17224598
TI  - Canadian guidelines on sexually transmitted infections, 2006.

PMID- 17224599
TI  - Auricular acupuncture for pain relief after ambulatory knee surgery: a randomized
      trial.
AB  - BACKGROUND: Auricular acupuncture is a promising method for postoperative pain
      relief. However, there is no evidence for its use after ambulatory surgery. Our
      aim was to test whether auricular acupuncture is better than invasive needle
      control for complementary analgesia after ambulatory knee surgery. METHODS: One
      hundred and twenty patients undergoing ambulatory arthroscopic knee surgery under
      standardized general anesthesia were randomly assigned to receive auricular
      acupuncture or a control procedure. Fixed indwelling acupuncture needles were
      inserted before surgery and retained in situ until the following morning.
      Postoperative rescue analgesia was directed to achieve pain intensity less than
      40 mm on a 100-mm visual analogue scale. The primary outcome measure was the
      postoperative requirement for ibuprofen between surgery and examination the
      following morning. RESULTS: Intention-to-treat analysis showed that patients from
      the control group (n = 59) required more ibuprofen than patients from the
      auricular acupuncture group (n = 61): median (interquartile range) 600 (200-800)
      v. 200 (0-600) mg (p = 0.012). Pain intensity on a visual analogue scale was
      similar in both groups at all time points registered. The majority of patients in
      both groups believed that they had received true acupuncture and wanted to repeat
      it in future. INTERPRETATION: Auricular acupuncture reduced the requirement for
      ibuprofen after ambulatory knee surgery relative to an invasive needle control
      procedure.

PMID- 17224600
TI  - Auricular acupuncture for analgesia after arthroscopy.

PMID- 17224601
TI  - Diabetes care in developing countries.

PMID- 17224602
TI  - Local thoughts on global actions.

PMID- 17224603
TI  - Accessible health care.

PMID- 17224604
TI  - Quality of care evaluation in France.

PMID- 17224605
TI  - Caring for young adults with diabetes.

PMID- 17224606
TI  - Mutual regulation of Crl and Fur in Escherichia coli W3110.
AB  - The small regulatory protein Crl controls the expression of curli. Recently we
      have shown that Crl interacts directly with one of the most global regulators of
      Escherichia coli, the stress-related sigma factor RpoS, suggesting a more global
      role for Crl. We show here by a proteomics analysis that the expression of at
      least nine cellular proteins was considerably modified when Crl was
      overexpressed. We assessed the part of transcriptional and post-transcriptional
      regulation for five of these genes. The results showed that Crl regulates the
      expression of another global regulator, the central regulator of iron
      homeostasis, Fur. A molecular analysis revealed that Crl and Fur affect their own
      and each other's expression. We provide physical evidence for the binding of Fur
      to the crl and fur promoter regions. Crl modulated the affinity of Fur at the fur
      promoter but not at the crl promoter. The triad RpoS-Crl-Fur may thus represent
      the centerpiece of a global regulatory system of response to different stresses.

PMID- 17224607
TI  - The Crl-RpoS regulon of Escherichia coli.
AB  - The RpoS subunit of RNA polymerase controls the expression of numerous genes
      involved in stationary phase and in response to different stress conditions. The
      regulatory protein Crl increases the activity of RpoS by direct interaction with
      the RpoS holoenzyme. To define the extent of the Crl regulon, we used two
      dimensional SDS-PAGE to measure the role of Crl in regulating the expression of
      the Escherichia coliproteome in stationary phase at 30 degrees C. By comparing
      the proteome of four strains (wild type, crl(-), rpoS(-), and crl(-)rpoS(-)), we
      observed that the intensity of 74 spots was modified in at least one mutant
      context. 62 spots were identified by mass spectrometry and correspond to 40
      distinct proteins. They were classified in four main categories: DNA metabolism,
      central metabolism, response to environmental modifications, and miscellaneous.
      Three proteins were specifically involved in quorum sensing: TnaA (the
      tryptophanase that converts tryptophan to indole), WrbA (Trp repressor-binding
      protein), and YgaG (homologous to LuxS, autoinducer-2 synthase). Because little
      is known about the regulation of Crl expression, we investigated the influence of
      diffusible molecules on the expression of Crl. Using Western blotting
      experiments, we showed that, at 30 degrees C, a diffusible molecule(s) produced
      during the transition phase between the exponential and stationary phases induces
      a premature expression of Crl. Indole was tested as one of the potential
      candidates: at 37 degrees C, it is present in the extracellular medium at a
      constant concentration, but at 30 degrees C, its concentration peaks during the
      transition phase. When indole was added to the culture medium, it also induced
      prematurely the expression of Crl at both the transcriptional and translational
      levels in a Crl-dependent manner. Crl may thus be considered a new environmental
      sensor via the indole concentration.

PMID- 17224608
TI  - Spontaneous reconstitution of discoidal HDL from sphingomyelin-containing model
      membranes by apolipoprotein A-I.
AB  - Nascent HDL is known to be formed by the interaction of apolipoprotein A-I (apoA
      I) with transmembrane ABCA1, but the molecular mechanism by which nascent HDL
      forms is less well understood. Here, we studied how reconstituted high density
      lipoprotein (rHDL) forms spontaneously on the interaction of apoA-I with model
      membranes. The formation of rHDL from pure phosphatidylcholine (PC) large
      unilamellar vesicles (LUVs) proceeded very slowly at 37.0 degrees C, but
      sphingomyelin (SM) -rich PC/SM LUVs, which are in a gel/liquid-disordered phase
      (L(d) phase) at this temperature, were rapidly microsolubilized to form rHDL by
      apoA-I. The addition of cholesterol decreased the rate at which rHDL formed and
      induced the selective extraction of lipids by apoA-I, which preferably extracted
      lipids of L(d) phase rather than lipids of liquid-ordered phase. In addition,
      apoA-I extracted lipids from the outer and inner leaflets of LUVs simultaneously.
      These results suggest that the heterogeneous interface of the mixed membranes
      facilitates the insertion of apoA-I and induces L(d) phase-selective but leaflet
      nonselective lipid extraction to form rHDL; they are compatible with recent cell
      works on apoA-I-dependent HDL generation.

PMID- 17224609
TI  - Selection and fusion of color models for image feature detection.
AB  - The choice of a color model is of great importance for many computer vision
      algorithms (e.g., feature detection, object recognition, and tracking) as the
      chosen color model induces the equivalence classes to the actual algorithms. As
      there are many color models available, the inherent difficulty is how to
      automatically select a single color model or, alternatively, a weighted subset of
      color models producing the best result for a particular task. The subsequent
      hurdle is how to obtain a proper fusion scheme for the algorithms so that the
      results are combined in an optimal setting. To achieve proper color model
      selection and fusion of feature detection algorithms, in this paper, we propose a
      method that exploits nonperfect correlation between color models or feature
      detection algorithms derived from the principles of diversification. As a
      consequence, a proper balance is obtained between repeatability and
      distinctiveness. The result is a weighting scheme which yields maximal feature
      discrimination. The method is verified experimentally for three different image
      feature detectors. The experimental results show that the fusion method provides
      feature detection results having a higher discriminative power than the standard
      weighting scheme. Further, it is experimentally shown that the color model
      selection scheme provides a proper balance between color invariance
      (repeatability) and discriminative power (distinctiveness).

PMID- 17224610
TI  - The gray-code filter kernels.
AB  - In this paper, we introduce a family of filter kernels--the Gray-Code Kernels
      (GCK) and demonstrate their use in image analysis. Filtering an image with a
      sequence of Gray-Code Kernels is highly efficient and requires only two
      operations per pixel for each filter kernel, independent of the size or dimension
      of the kernel. We show that the family of kernels is large and includes the Walsh
      Hadamard kernels, among others. The GCK can be used to approximate any desired
      kernel and, as such forms, a complete representation. The efficiency of
      computation using a sequence of GCK filters can be exploited for various real
      time applications, such as, pattern detection, feature extraction, texture
      analysis, texture synthesis, and more.

PMID- 17224611
TI  - Supervised learning of semantic classes for image annotation and retrieval.
AB  - A probabilistic formulation for semantic image annotation and retrieval is
      proposed. Annotation and retrieval are posed as classification problems where
      each class is defined as the group of database images labeled with a common
      semantic label. It is shown that, by establishing this one-to-one correspondence
      between semantic labels and semantic classes, a minimum probability of error
      annotation and retrieval are feasible with algorithms that are 1) conceptually
      simple, 2) computationally efficient, and 3) do not require prior semantic
      segmentation of training images. In particular, images are represented as bags of
      localized feature vectors, a mixture density estimated for each image, and the
      mixtures associated with all images annotated with a common semantic label pooled
      into a density estimate for the corresponding semantic class. This pooling is
      justified by a multiple instance learning argument and performed efficiently with
      a hierarchical extension of expectation-maximization. The benefits of the
      supervised formulation over the more complex, and currently popular, joint
      modeling of semantic label and visual feature distributions are illustrated
      through theoretical arguments and extensive experiments. The supervised
      formulation is shown to achieve higher accuracy than various previously published
      methods at a fraction of their computational cost. Finally, the proposed method
      is shown to be fairly robust to parameter tuning.

PMID- 17224612
TI  - Robust object recognition with cortex-like mechanisms.
AB  - We introduce a new general framework for the recognition of complex visual
      scenes, which is motivated by biology: We describe a hierarchical system that
      closely follows the organization of visual cortex and builds an increasingly
      complex and invariant feature representation by alternating between a template
      matching and a maximum pooling operation. We demonstrate the strength of the
      approach on a range of recognition tasks: From invariant single object
      recognition in clutter to multiclass categorization problems and complex scene
      understanding tasks that rely on the recognition of both shape-based as well as
      texture-based objects. Given the biological constraints that the system had to
      satisfy, the approach performs surprisingly well: It has the capability of
      learning from only a few training examples and competes with state-of-the-art
      systems. We also discuss the existence of a universal, redundant dictionary of
      features that could handle the recognition of most object categories. In addition
      to its relevance for computer vision, the success of this approach suggests a
      plausibility proof for a class of feedforward models of object recognition in
      cortex.

PMID- 17224613
TI  - On classification with incomplete data.
AB  - We address the incomplete-data problem in which feature vectors to be classified
      are missing data (features). A (supervised) logistic regression algorithm for the
      classification of incomplete data is developed. Single or multiple imputation for
      the missing data is avoided by performing analytic integration with an estimated
      conditional density function (conditioned on the observed data). Conditional
      density functions are estimated using a Gaussian mixture model (GMM), with
      parameter estimation performed using both Expectation-Maximization (EM) and
      Variational Bayesian EM (VB-EM). The proposed supervised algorithm is then
      extended to the semisupervised case by incorporating graph-based regularization.
      The semisupervised algorithm utilizes all available data-both incomplete and
      complete, as well as labeled and unlabeled. Experimental results of the proposed
      classification algorithms are shown.

PMID- 17224614
TI  - Optimal separable algorithms to compute the reverse euclidean distance
      transformation and discrete medial axis in arbitrary dimension.
AB  - In binary images, the Distance Transformation (DT) and the geometrical skeleton
      extraction are classic tools for shape analysis. In this paper, we present time
      optimal algorithms to solve the reverse Euclidean distance transformation and the
      reversible medial axis extraction problems for d-dimensional images. We also
      present a d-dimensional medial axis filtering process that allows us to control
      the quality of the reconstructed shape.

PMID- 17224615
TI  - Skeleton pruning by contour partitioning with discrete curve evolution.
AB  - In this paper, we introduce a new skeleton pruning method based on contour
      partitioning. Any contour partition can be used, but the partitions obtained by
      Discrete Curve Evolution (DCE) yield excellent results. The theoretical
      properties and the experiments presented demonstrate that obtained skeletons are
      in accord with human visual perception and stable, even in the presence of
      significant noise and shape variations, and have the same topology as the
      original skeletons. In particular, we have proven that the proposed approach
      never produces spurious branches, which are common when using the known skeleton
      pruning methods. Moreover, the proposed pruning method does not displace the
      skeleton points. Consequently, all skeleton points are centers of maximal disks.
      Again, many existing methods displace skeleton points in order to produces pruned
      skeletons.

PMID- 17224616
TI  - Space-time completion of video.
AB  - This paper presents a new framework for the completion of missing information
      based on local structures. It poses the task of completion as a global
      optimization problem with a well-defined objective function and derives a new
      algorithm to optimize it. Missing values are constrained to form coherent
      structures with respect to reference examples. We apply this method to space-time
      completion of large space-time "holes" in video sequences of complex dynamic
      scenes. The missing portions are filled in by sampling spatio-temporal patches
      from the available parts of the video, while enforcing global spatio-temporal
      consistency between all patches in and around the hole. The consistent completion
      of static scene parts simultaneously with dynamic behaviors leads to realistic
      looking video sequences and images. Space-time video completion is useful for a
      variety of tasks, including, but not limited to: 1) Sophisticated video removal
      (of undesired static or dynamic objects) by completing the appropriate static or
      dynamic background information. 2) Correction of missing/corrupted video frames
      in old movies. 3) Modifying a visual story by replacing unwanted elements. 4)
      Creation of video textures by extending smaller ones. 5) Creation of complete
      field-of-view stabilized video. 6) As images are one-frame videos, we apply the
      method to this special case as well.

PMID- 17224617
TI  - Segmenting, modeling, and matching video clips containing multiple moving
      objects.
AB  - This paper presents a novel representation for dynamic scenes composed of
      multiple rigid objects that may undergo different motions and are observed by a
      moving camera. Multiview constraints associated with groups of affine-covariant
      scene patches and a normalized description of their appearance are used to
      segment a scene into its rigid components, construct three-dimensional models of
      these components, and match instances of models recovered from different image
      sequences. The proposed approach has been applied to the detection and matching
      of moving objects in video sequences and to shot matching, i.e., the
      identification of shots that depict the same scene in a video clip.

PMID- 17224618
TI  - Performance generalization in biometric authentication using joint user-specific
      and sample bootstraps.
AB  - Biometric authentication performance is often depicted by a detection error trade
      off (DET) curve. We show that this curve is dependent on the choice of samples
      available, the demographic composition and the number of users specific to a
      database. We propose a two-step bootstrap procedure to take into account the
      three mentioned sources of variability. This is an extension to the Bolle et
      al.'s bootstrap subset technique. Preliminary experiments on the NIST2005 and
      XM2VTS benchmark databases are encouraging, e.g., the average result across all
      24 systems evaluated on NIST2005 indicates that one can predict, with more than
      75 percent of DET coverage, an unseen DET curve with eight times more users.
      Furthermore, our finding suggests that with more data available, the confidence
      intervals become smaller and, hence, more useful.

PMID- 17224619
TI  - Camera calibration from images of spheres.
AB  - This paper introduces a novel approach for solving the problem of camera
      calibration from spheres. By exploiting the relationship between the dual images
      of spheres and the dual image of the absolute conic (IAC), it is shown that the
      common pole and polar with regard to the conic images of two spheres are also the
      pole and polar with regard to the IAC. This provides two constraints for
      estimating the IAC and, hence, allows a camera to be calibrated from an image of
      at least three spheres. Experimental results show the feasibility of the proposed
      approach.

PMID- 17224620
TI  - On the impact of dissimilarity measure in k-modes clustering algorithm.
AB  - This correspondence describes extensions to the k-modes algorithm for clustering
      categorical data. By modifying a simple matching dissimilarity measure for
      categorical objects, a heuristic approach was developed in [4], [12] which allows
      the use of the k-modes paradigm to obtain a cluster with strong intrasimilarity
      and to efficiently cluster large categorical data sets. The main aim of this
      paper is to rigorously derive the updating formula of the k-modes clustering
      algorithm with the new dissimilarity measure and the convergence of the algorithm
      under the optimization framework.

PMID- 17224621
TI  - Direct curvature scale space: theory and corner detection.
AB  - The Curvature Scale Space (CSS) technique is considered to be a modern tool in
      image processing and computer vision. Direct Curvature Scale Space (DCSS) is
      defined as the CSS that results from convolving the curvature of a planar curve
      with a Gaussian kernel directly. In this paper we present a theoretical analysis
      of DCSS in detecting corners on planar curves. The scale space behavior of
      isolated single and double corner models is investigated and a number of model
      properties are specified which enable us to transform a DCSS image into a tree
      organization and, so that corners can be detected in a multiscale sense. To
      overcome the sensitivity of DCSS to noise, a hybrid strategy to apply CSS and
      DCSS is suggested.

PMID- 17224622
TI  - Autophagy in the invading pathogen.
AB  - Autophagic degradation is of central importance to eukaryotic biology and has
      been implicated in a diverse array of developmental, differentiation, and disease
      related events in higher eukaryotes. We recently investigated the significance of
      autophagy in the opportunistic fungal pathogen Candida albicans. Surprisingly our
      results demonstrate that autophagy is not required for C. albicans yeast-hypha or
      chlamydospore differentiation. Furthermore, a Candida mutant blocked in autophagy
      had no detectable virulence defect during interaction with a macrophage like cell
      line, or in a murine model of disseminated candidiasis. Herein we consider these
      results in the context of the pathogenic eukaryote, and raise important questions
      which remain to be addressed.

PMID- 17224623
TI  - AMP-activated protein kinase and autophagy.
AB  - Autophagy is inhibited by TOR-dependent signaling. Interruption of signalling by
      rapamycin is known to stimulate autophagy, both in mammalian cells and in yeast.
      However, inactivation of TOR by AMPK has yielded controversial results in the
      literature with regard to its effect on autophagy: activation of autophagy in
      yeast but inhibition in hepatocytes. In a recent study, carried out with
      hepatocytes, HT-29 cells, and HeLa cells, the possible role of AMPK in the
      control of mammalian autophagy was reexamined. The data suggest that in mammalian
      cells, as in yeast, AMPK is required for autophagy.

PMID- 17224624
TI  - CD40-TRAF6 and autophagy-dependent anti-microbial activity in macrophages.
AB  - A fundamental question in host-pathogen interaction is to determine if the immune
      system activates fusion with the lysosomes to eradicate pathogens. We recently
      reported that this task is accomplished by the interaction between CD40 expressed
      on macrophages and CD154 expressed on activated CD4+ T cells. CD40 stimulation of
      macrophages induces vacuole-lysosome fusion through autophagy and results in
      killing of the obligate intracellular pathogen Toxoplasma gondii. This response
      is independent of IFN-gamma, STAT1 and p47 GTPases. We now report that vacuole
      lysosome fusion is dependent on synergy between TRAF6 signaling downstream of
      CD40 and TNF-alpha. These studies identified a new paradigm by which T cells
      eradicate an intracellular pathogen within macrophages.

PMID- 17224625
TI  - Methods for monitoring autophagy from yeast to human.
AB  - The increasing interest in autophagy in a wide range of organisms, accompanied by
      an ever-growing influx of researchers into this field, necessitates a good
      understanding of the methodologies available to monitor this process. In this
      review we discuss current approaches that can be used to follow the overall
      process of autophagy, as well as individual steps, from yeast to human. The
      majority of the review considers methods that apply to macroautophagy; however,
      we also consider alternative types of degradation including chaperone-mediated
      autophagy and microautophagy. This information is meant to provide a resource for
      newcomers as well as a stimulus for experienced researchers who may be prompted
      to develop additional assays to examine autophagy-related pathways.

PMID- 17224626
TI  - Everolimus-induced mTOR inhibition selectively depletes macrophages in
      atherosclerotic plaques by autophagy.
AB  - Current pharmacological approaches to stabilize nonobstructive rupture-prone
      atherosclerotic plaques have only partially reduced the incidence of acute
      coronary syndromes and sudden death. Macrophages in these vulnerable plaques play
      a pivotal role in plaque destabilization, whereas smooth muscle cells promote
      plaque stability. In a recent study, we report that implantation of stents
      eluting everolimus, a mammalian target of rapamycin (mTOR) inhibitor, in
      atherosclerotic arteries of cholesterol-fed rabbits, led to a marked reduction in
      macrophage content without altering the amount of smooth muscle cells. Our in
      vitro studies showed that treatment of macrophages and smooth muscle cells with
      everolimus induced inhibition of translation of both cell types. However, cell
      death occurred only in macrophages and was characterized by bulk degradation of
      long-lived proteins, processing of microtubule associated protein light chain 3
      (LC3), and cytoplasmic vacuolization, which are all markers of autophagy.
      Everolimus-induced autophagy was mediated by mTOR inhibition because cell
      viability was not affected using tacrolimus, an mTOR independent everolimus
      analogue. These results provide proof-of-principle that macrophages in the
      vascular wall can be selectively cleared via induction of autophagy by mTOR
      inhibition. Therefore, stent-based delivery of an mTOR inhibitor may be a
      promising novel strategy for treatment of vulnerable atherosclerotic plaques.

PMID- 17224627
TI  - A novel type of autophagy occurs together with vacuole genesis in miniprotoplasts
      prepared from tobacco culture cells.
AB  - Mature plant cells have large vacuoles. But how these vacuoles are formed has not
      been fully understood. It has been reported that autophagy is involved in the
      genesis of plant vacuoles. Thus we examined whether autophagy occurs in the
      vacuole genesis of a plant cell model called miniprotoplasts, in which
      preexisting large vacuoles have been removed. We prepared miniprotoplasts from
      tobacco culture cells (BY-2) and observed the formation of vacuoles by light and
      electron microscopy. The miniprotoplasts had few vacuoles immediately after
      preparation, but had large vacuoles after 1 to 2 d. When the cysteine protease
      inhibitor E-64c or E-64d was added to culture media, almost all vacuoles formed
      contained materials of cytoplasmic origin. This result suggests that autophagy
      occurs together with the genesis of the vacuoles in miniprotoplasts. 3
      Methyladenine and phosphatidylinositol 3-kinase inhibitors such as wortmannin and
      LY294002, all of which block starvation?induced autophagy in tobacco culture
      cells and constitutive autophagy in Arabidopsis root cells, did not affect the
      autophagy in miniprotoplasts. Thus the form of autophagy in miniprotoplasts is
      probably different from the form of autophagy that arises as a result of sucrose
      starvation and constitutive autophagy in root tip cells. The causal connection
      between autophagy and vacuole genesis in miniprotoplasts was not clarified in
      this study.

PMID- 17224628
TI  - Calpain as a novel regulator of autophagosome formation.
AB  - Ubiquitously expressed micro- and m-calpain proteases consist of 80-kDa catalytic
      subunits encoded by the Capn1 and Capn2 genes, respectively, and a common 28-kDa
      regulatory subunit encoded by the calpain small 1 (Capns1) gene. The micro- and m
      calpain proteases have been implicated in both pro- or anti-apoptotic functions.
      We have found that Capns1 depletion is coupled to increased sensitivity to
      apoptosis triggered by a number of autophagy-inducing stimuli in mammalian cells.
      Therefore we investigated the involvement of calpains in autophagy using MEFs
      derived from Capns1 knockout mice and Capns1 depleted human cells as model
      systems. We found that autophagy is impaired in Capns1-deficient cells by
      immunostaining of the endogenous autophagosome marker LC3 and electron microscopy
      experiments. Accordingly, the enhancement of lysosomal activity and long-lived
      proteins degradation, normally occurring upon starvation, are also reduced. In
      Capns1-depleted cells ectopic LC3 accumulates in early endosome-like vesicles
      that might represent a salvage pathway for protein degradation when autophagy is
      defective.

PMID- 17224629
TI  - HIF-1 regulation of chondrocyte apoptosis: induction of the autophagic pathway.
AB  - The goal of our investigation was to explore the mechanism by which hypoxia
      regulates growth plate chondrocyte survival. At low O2 tension, chondrocytes were
      refractory to a staurosporine (i.e., apoptosis-inducing) challenge. To determine
      whether hypoxic survival was due to the expression of HIF-1, we evaluated the
      response of HIF silenced cells to staurosporine. Both, silenced cells and control
      chondrocytes were equally sensitive to the apoptogen challenge. To learn if
      resistance was mediated by the proteins of the autophagic pathway, we examined
      the expression of Beclin 1 and LC3. Both proteins were present in the growth
      plate as well as in N1511 chondrocytes. Moreover, silencing of Beclin 1 resulted
      in enhanced chondrocyte death. Thus, this gene served to maintain chondrocyte
      survival activity. Besides serving a cytoprotective role, it is known that
      autophagy can function in cell death. Accordingly, to ascertain if autophagy
      might also sensitize cells to apoptosis, we activated autophagy and examined
      viability following exposure to an apoptogen. Treatment with the autophagy
      inhibitor 3-methyladenine rendered the chondrocytes refractory to killing,
      suggesting that sustained autophagy promoted cell death. We next examined
      expression of BID and caspase-8. When autophagy was suppressed, chondrocytes
      promoted caspase-8 activation and activated BID. Finally, we explored the
      relationship between HIF-1 and Beclin 1. We noted a decrease in Beclin 1
      expression and loss of caspase-8 activation in HIF silenced cells and Beclin 1
      Bcl-2 association was maintained upon serum starvation. This study indicates that
      HIF-1 serves to regulate both autophagy and apoptosis.

PMID- 17224630
TI  - A novel cancer therapy approach targeting microtubule function.

PMID- 17224631
TI  - Adenoviral-Vector Based siRNA for Mutant K-ras as a Promising Tool for Lung
      Cancer Gene Therapy: A License to Kill.

PMID- 17224632
TI  - Suicide gene delivery by calcium phosphate nanoparticles: a novel method of
      targeted therapy for gastric cancer.

PMID- 17224633
TI  - Disruption of the Fanconi anemia pathway in human cancer in the general
      population.

PMID- 17224634
TI  - A review of topoisomerase inhibition in lung cancer.
AB  - Lung cancer is the leading cause of cancer deaths among both males and females.
      Although there have been several advances in the treatment armamentarium, both
      small cell and nonsmall cell lung cancer continue to be prognostically poor
      diseases that are refractory to therapy. Several of the regimens involved in
      treating the disease include drugs that inhibit the topoisomerase enzymes, whose
      specific role in relieving torsional strain on DNA to facilitate replication and
      transcription has long been known. Topoisomerase inhibition, however, has
      increasingly gained attention because of its efficacy in disease stabilization in
      lung cancer, with continued elaboration of its exact mechanism in lung cancer
      therapy. This review presents the biology and molecular mechanics of the
      topoisomerase enzymes, as well as the effect of their inhibition in SCLC and
      NSCLC, with discussion of specific drugs and the data to support and explain its
      use as a chemotherapeutic target in lung cancer.

PMID- 17224635
TI  - Tissue specific expression of suicide genes delivered by nanoparticles inhibits
      gastric carcinoma growth.
AB  - Developing an efficient and safe strategy to introduce a therapeutic gene into
      targeting cells in vivo is a key issue in cancer gene therapy nowadays. Novel non
      viral gene carriers, such as nanoparticles, have been shown to be able to deliver
      DNA into cancer cells efficiently. Suicide gene therapy has been demonstrated to
      be effective in inhibiting tumor growth, however, the lack of tumor specificity
      limits its application in clinic. Developing a targeting system for suicide gene
      is an attractive strategy in cancer gene therapy. In this study, the CMV enhancer
      and carcinoembryonic antigen (CEA) promoter was fused to a chimeric suicide gene
      yCDglyTK. This construct was delivered into SGC7901 gastric cancer cells using
      calcium phosphate nanoparticles (CPNPs). The expression of yCDglyTK in SGC7901
      cells was confirmed by RT-PCR and western blot. Immunofluorescence experiments
      showed that yCDglyTK is only expressed in CEA-positive cancer cells, but not in
      CEA-negative cells. The expression of yCDglyTK induced cancer cell death
      following the addition of the prodrug 5-FC, and also elicit "bystander effect" to
      kill the neighboring cells. Intratumoral injection of CPNP-yCDglyTK complex
      followed by administration of 5-FC produced marked regression in gastric cancer
      xenografts. Taken together, our study suggests that the combination of calcium
      phosphate nanoparticles and suicide gene therapy represents a novel approach for
      targeting gastric cancer gene therapy.

PMID- 17224636
TI  - Tumor progression and metastasis from genetic to microenvironmental determinants:
      a workshop of the tumor progression and metastasis NIH study section in honor of
      Dr. Martin L. Padarathsingh, May 31, 2006, Georgetown, Washington, DC.

PMID- 17224637
TI  - PPARgamma agonists follow an unknown TRAIL in lung cancer.

PMID- 17224638
TI  - Polyphenols in breast cancer treatment.

PMID- 17224639
TI  - TMPRSS2:ERG gene fusion a new genetic marker for prostate cancer progression.

PMID- 17224640
TI  - Colorectal cancer: new advances in immunotherapy.
AB  - Colorectal cancer remains the second leading cause of cancer-related mortality in
      the United States. Although surgical resection is still the primary treatment for
      colorectal cancer, in recent years, there has been a remarkable progress in the
      development of new therapies to treat colorectal cancer. Response rates have
      increased substantially and new immunotherapeutic approaches are shedding new
      light in the battle against the disease. This review will focus on the current
      immunotherapeutic approaches being developed and will discuss clinical data for
      some of these new treatments.

PMID- 17224641
TI  - Slow acetylator genotype of N-acetyl transferase2 (NAT2) is associated with
      increased susceptibility to gallbladder cancer: the cancer risk not modulated by
      gallstone disease.
AB  - This study comprised 124 consecutive cases of proven GBC and 147 healthy
      controls. NAT2 polymorphisms were carried out using PCR-RFLP method. The NAT2
      slow acetylator genotype was significantly associated with risk of GBC (OR 3.4,
      95% CI =1.9-5.7 p = 0.000007). The NAT2 2*6 and 2*7 allele frequencies were
      higher in GBC and conferred significant risk of cancer (OR 1.9, 95% Cl = 1.2-2.9,
      p= 0.006; OR, 2.9, 95% Cl = 1.6-5.2, p = 0.0001). The haplotypes 2, 1, 1 and 1,
      2, 1 were significantly higher (OR 3.7 95% Cl 2.1-7.0, p = 0.00001; OR 1.8 95% Cl
      =1.1-2.8, p = 0.008) in GBC. The risk of slow acetylator phenotype in GBC
      patients with or without gallstones was similar. These results suggest that NAT2
      slow acetylator phenotype influences the susceptibility of gallbladder cancer and
      the risk is not modulated by gallstone disease.

PMID- 17224642
TI  - Diagnostic efficacy and safety of 99mtc-labeled monoclonal antibody ior c5 in
      patients with colorectal and anal carcinomas: final report clinical trial phase
      I/II.
AB  - Monoclonal antibody (mAb) ior c5 is an IgG1, which recognizes a glycoprotein
      tumor specific antigen IOR C2 over expressed in the surface of colon and ovarian
      cancer cells. The aim of the present work was to evaluate the diagnostic efficacy
      of the 99mTc-labeled mAb ior c5 for the detection of colorectal tumors, its
      metastases and recurrences. METHODS: Eighty six patients with colorectal or anal
      cancer, mean age 57 +/- 13 yrs, were involved in a phase 1/11 multicentric, open
      clinical trial to assess the ability of Radioimmunoscintigraphy (RIS) with 99mTc-
      mAb ior c5 to detect those tumors. Seventy-four patients received 1 mg of c5
      labeled with 1480-1850 MBq to determinate diagnosis efficacy and safety of murine
      mAb by intravenously (i.v.) bolus injection (group 1). In order to evaluate
      pharmacokinetic, bio distribution and dosimetry of this radiolabel molecule, 12
      patients received 3 mg of labeled ior c5. Planar anterior and posterior images of
      the lesion sites and suspected metastases were acquired at 2, 4 and 18-24 hours
      after injection using a matrix size 128 x128 and 500 Kcounts per view. SPECT were
      scanned at 5 hr post-injection, using a 360' circular orbit with 64 images. HAMA
      response was measured in serum at 2, 4, 8 and 12 week post-administration.
      RESULTS: Labeling efficiency was (97.8 - 0.6) %. No adverse reactions or side
      effects were observed. Overall sensitivity, specificity, accuracy, positive and
      negative predictive values of the immunoscintigraphy were 95.80%, 100%, 96.51%,
      100.0% and 82.35%, respectively. Unknown metastases were detected in 37 of 86
      cases (43.02%). No HAMA response was found. CONCLUSIONS: Immunoscintigraphy with
      99mTc-labeled mAb ior c5 could be a useful procedure for the diagnosis and follow
      up of the patients with colorectal tumors, its metastasis and recurrences.

PMID- 17224643
TI  - Metastatic cancer cells from c-erbB-2 negative primary breast cancer maintain the
      original c-erbB-2/HIF1alpha phenotype.
AB  - The expression of c-erbB-2 and HIF1alpha proteins is linked with an aggressive
      tumor phenotype and poor survival in breast cancer. In the present study we
      investigated whether this ominous effect is a result of c-erbB-2/HIF1alpha
      expressing clone appearance within the primary tumor, by examining the c-erbB
      2/HIF1alpha expression status in the primary tumor, node metastasis and cancer
      cells invading into the lymphovascular spaces. The metastasizing cancer cell
      clones, whether migrating to the lymph nodes or entering into the systemic
      circulation maintained the original c-erbB-2/HIF1alphaphenotype of the primary
      tumor. Migrating c-erbB-2/HIF1alpha negative tumors do so through activation of
      alternative biologic pathways and not through positive clone appearance. These
      results strongly support the concept that targeted therapies against c-erbB-2 or
      against HIF1alpha can be guided with precision by the primary tumor c-erbB
      2/HIF1alpha status without demanding the detection of the metastatic tumor
      phenotype.

PMID- 17224644
TI  - Bortezomib sensitizes human head and neck carcinoma cells SQ20B to radiation.
AB  - The proteasome inhibitor bortezomib was tested in a cell screen as a single agent
      with good efficacy in multiple hematologic and solid cancer cell lines. Phase
      II/III studies have supported the use of bortezomib in hematologic malignancies.
      In solid tumors, however, the results have been poor. There is data that
      bortezomib can induce PTEN expression resulting in down-regulation of PI3K-Akt
      signaling. We and others have shown that down-regulation of Akt results in
      radiation sensitization. We therefore evaluated the use of bortezomib in the head
      and neck cancer cell line SQ20B as a radiation sensitizer. SQ20B have a
      constitutively active mutation in EGFR resulting in a robust Akt response. We
      found that 10 nM of bortezomib decreased Akt signaling to almost undetectable.
      This same concentration decreased the surviving fraction after 2 Gy (SF2) from
      0.77 to 0.45. Given that radiation is usually given at 2 Gy increments daily for
      30 or more treatments, the exponential difference in log kill could be as high as
      7 logs. The dose of bortezomib is also 2 logs less as a sensitizer than that
      required for single agent efficacy. Further studies should be done to explore
      this model in vivo.

PMID- 17224645
TI  - Bcl2/bcl-xL inhibitor engenders apoptosis and increases chemosensitivity in
      mesothelioma.
AB  - Mesothelioma is a neoplasm of the pleura that is currently incurable by
      conventional therapies. Previously, we demonstrated that mesothelioma
      overexpresses BCL-X(L), an anti-apoptotic member of the BCL-2 family. In
      addition, we have shown that down regulation of BCL-X(L) using a BCL-X(L)
      antisense oligonucleotide engenders mesothelioma apoptotic cell death in vitro
      and in vivo. The purpose of this study is to evaluate the efficacy of bcl2/bcl
      x(L) inhibitor, 2-methoxy antimycin A3, in inducing apoptosis and increasing
      chemo-sensitivity in vitro and in vivo. Several bcl-x(L) high-expression tumor
      cell lines and one normal human cell line were exposed to 2-methoxy antimycin A3.
      2-methoxy antimycin A3 demonstrated significant growth inhibition only in these
      tumor cell lines, with little effect on normal human cells. Treatment with 2
      methoxy antimycin A3 alone resulted in a dramatic increase in the induction of
      apoptosis in the cancer cells. Apoptosis occurs through decreasing mitochondrial
      membrane potential and caspase activation. Notably, treatment with 2-methoxy
      antimycin A3 does not alter BCL-2 family protein expression. Synergistic
      inhibition of tumor growth by the coadministration of cisplatin and 2-methoxy
      antimycin A3 was observed in both in vitro and in vivo experiments. Together,
      these findings indicate that exposure of cancer cells to small molecule Bcl
      2/x(L) inhibitors such as 2-methoxy antimycin A3 alone, or in the combination
      with other chemotherapeutics, may represent a novel therapeutic strategy in
      treatment of cancer, especially mesothelioma.

PMID- 17224646
TI  - Analysis of apoptosome dysregulation in pancreatic cancer and of its role in
      chemoresistance.
AB  - The apoptosome is a multiprotein complex mediating the mitochondrial pathway of
      cell death. Its importance during development has been clearly demonstrated by
      knocking out key genes in mouse. APAF1 is the core protein of the apoptosome and
      its dosage is also critical in various cancer types, i.e., melanoma, germ line
      tumor, gastrointestinal cancer and B-type chronic lymphocytic leukemia. This is
      generally due to inactivation of the APAF1 locus by epigenetic phenomena or by
      activity of promoter regulators. We investigated the putative roles of the
      apoptosome in pancreatic ductal adenocarcinoma (PDAC). We found that both APAF1
      mRNA and protein are dysregulated in human PDAC samples. Similarly, several PDAC
      cell lines exhibited variable levels of both APAF1 protein and mRNA. The response
      to cell death induction and its biochemical features were assessed by treatment
      of each line with commonly used chemotherapeutic agents. We found that the
      apoptosome pathway was not functional in most cell lines upon cytochrome c
      release from mitochondria. In addition, we restored APAF1 and Caspase-9 dosage in
      Panc-1 cells, where the apoptosome is downregulated, by overexpressing the murine
      cDNA of the two molecules, and we improved the death response to chemotherapeutic
      agents.

PMID- 17224647
TI  - Effect of celecoxib on E-cadherin, VEGF, Microvessel density and apoptosis in
      gastric cancer.
AB  - Cyclooxygenase-2 (COX-2) plays a crucial role in the development and invasion of
      gastric cancer. COX-2 inhibitors have been shown to be chemopreventive against
      gastrointestinal cancers. In vitro studies have suggested that the mechanisms may
      be related to induction of apoptosis and inhibition of angiogenesis. COX-2 may
      also have impact on E-cadherin. In our study we investigate the effect of
      Celecoxib on expression of E-cadherin and serum soluble E-cadherin, as well as on
      apoptosis and angiogenesis in patients with gastric cancer. Fifty nine gastric
      cancer patients were randomly divided into two groups: Surgery group (n = 22), in
      which patients underwent surgical resection after diagnosis, and Celecoxib +
      Surgery group (n = 37), in which patients received oral Celecoxib 200 mg twice
      daily for 7 days before curative resection. Twenty healthy subjects (Healthy
      controls) were recruited as normal controls. After curative resection, COX-2, E
      cadherin, VEGF, and MVD were detected by immunohistochemistry. Serum soluble E
      cadherin was quantitatively measured using a commercially available enzyme-linked
      immunosorbent assay kit. Apoptosis was determined by TUNEL assay. Significantly
      decreased expression of COX-2, increased E-cadherin and apoptosis, decreased VEGF
      and MVD were observed in gastric cancer tissues from patients receiving Celecoxib
      compared to Surgery group. Compared to Healthy controls, the serum soluble E
      cadherin levels were higher in gastric cancer patients which were decreased by
      Celecoxib. This in vivo study demonstrated that Celecoxib induces apoptosis and
      inhibit angiogenesis of gastric cancer. Its impact on E-cadherin may suggest that
      this agent may suppress the invasion of advanced gastric cancer.

PMID- 17224648
TI  - Expression of extracellular matrix metalloproteinase inducer (EMMPRIN/CD147) in
      pancreatic neoplasm and pancreatic stellate cells.
AB  - EMMPRIN (extracellular matrix metalloproteinase inducer, CD147) participates in
      the progression of various malignancies by stimulating the synthesis of specific
      matrix metalloproteinases (MMP) from peritumoral fibroblasts. In the present
      study, the expression and functional role of EMMPRIN was investigated in
      pancreatic neoplasm. QRT-PCR, immunohistochemistry, immunoblot, and ELISA
      analyses were used to analyze the expression, localization, and release of
      EMMRPIN. Silencing of EMMPRIN was performed using siRNA oligonucleotides, and
      functional consequences were assessed using growth assays, invasion assays, as
      well as MMP1/MMP2 and VEGF ELISA. EMMPRIN mRNA levels were 2.2-fold increased in
      pancreatic cancer (n = 52) and 2.0-3.5-fold increased in other pancreatic
      neoplasm (n = 105), but unchanged in chronic pancreatitis (n = 10) compared to
      normal pancreatic tissues (n = 9). Strong and predominantly membranous
      immunostaining was observed in the cancer cells and surrounding stromal cells.
      EMMPRIN serum levels were also significantly increased in pancreatic cancer
      patients (n = 44) (4.13 +/- 0.28 ng/ml) with an AUC of 0.97 compared to healthy
      volunteers (n = 29) (0.95 +/- 0.16 ng/ml; p < 0.0001) and with an AUC of 0.74
      compared to chronic pancreatitis patients (n = 20) (2.98 +/- 0.5 ng/ml; p =
      0.0021). EMMPRIN silencing did not significantly affect anchorage-dependent or 
      independent growth of pancreatic cancer cells. In contrast, EMMPRIN silencing in
      pancreatic stellate cells slightly repressed VEGF and MMP2 levels but strongly
      increased pro-MMP1 expression under coculture conditions. In conclusion,
      Increased EMMPRIN expression is present in different pancreatic neoplasm, likely
      representing a tumor-specific reaction with the potential to modulate the tumor
      microenvironment rather than a mere reflection of an activated stroma.

PMID- 17224649
TI  - Clinical and mechanistic aspects of glucocorticoid-induced chemotherapy
      resistance in the majority of solid tumors.
AB  - BACKGROUND: Glucocorticoids have been used widely in conjunction with cancer
      therapy due to their ability to induce apoptosis in hematological cells and to
      prevent nausea and emesis. However, recent data including ours, suggest induction
      of therapy-resistance by glucocorticoids in solid tumors, although it is unclear
      whether this happens only in few carcinomas or is a more common cell type
      specific phenomenon. MATERIAL AND METHODS: We performed an overall statistical
      analysis of our new and recent data with 157 tumor probes evaluated in vitro, ex
      vivo and in vivo. The effect of glucocorticoids on apoptosis, viability and cell
      cycle progression under diverse clinically important questions was examined.
      RESULTS: New in vivo results demonstrate glucocorticoid-induced chemotherapy
      resistance in xenografted prostate cancer. In an overall statistical analysis we
      found glucocorticoid-induced resistance in 89% of 157 analysed tumor samples.
      Resistance is common for several cytotoxic treatments and for several
      glucocorticoid-derivatives and due to an inhibition of apoptosis, promotion of
      viability and cell cycle progression. Resistance occurred at clinically
      achievable peak plasma levels of patients under anti-emetic glucocorticoid
      therapy and below, lasted for a long time, after one single dose, but was
      reversible upon removal of glucocorticoids. Two nonsteroidal alternative anti
      emetic agents did not counteract anticancer treatment and may be sufficient to
      replace glucocorticoids in cotreatment of carcinoma patients. CONCLUSION: These
      data demonstrate the need for prospective clinical studies as well as for
      detailed mechanistic studies of GC-induced cell-type specific pro- and anti
      apoptotic signalling.

PMID- 17224650
TI  - p63, cellular senescence and tumor development.
AB  - Deficiency of p63, a p53-related protein, causes severe defects in epithelial
      morphogenesis. Studies of p63-compromised mouse models reveal that p63 deficiency
      induces cellular senescence both in cultured cells and in vivo, through
      regulation p19(Arf)/p53 and p16(Ink4a)/Rb pathways. An extensive tumor study of
      p63-compromised mice demonstrated that p63 deficiency does not predispose to, but
      rather protects from, tumor development. These findings further implicate p63 as
      a negative regulator of the tumor suppressive mechanism of cellular senescence.

PMID- 17224651
TI  - p63-associated disorders.
AB  - Heterozygous mutations in the transcription factor gene p63 are causative for
      several syndromes, with ectodermal dysplasia, orofacial clefting and limb
      malformations as the key characteristics. Different combinations of these
      features are seen in five different syndromes, of which ectrodactyly, ectodermal
      dysplasia and cleft lip/palate syndrome (EEC) is the most common one. Mutations
      in p63 can also cause non-syndromic single malformations, such as split hand foot
      malformation (SHFM4) and isolated cleft lip (NSCL). In this article we will
      present an overview of diseases caused by mutations in the p63 gene and review
      the known pathogenic p63 gene mutations.

PMID- 17224652
TI  - Conflicting roles for p63 in skin development and carcinogenesis.
AB  - Epidermal morphogenesis is a complex process that culminates in the formation of
      a barrier that protects the organism from environmental substances and
      dehydration. p63, a transcription factor, is essential for normal epidermal
      morphogenesis as demonstrated by the failure of mice lacking p63 expression to
      develop an epidermis. However, since two independently generated p63(-/-) mouse
      models displayed different phenotypes, the role of p63 in epidermal morphogenesis
      has remained controversial. Furthermore, the tumor susceptibility phenotypes of
      both p63(-/-) mouse models were strikingly different. In this review, we discuss
      these conflicting findings and provide evidence for various roles of p63 in the
      epidermis under normal and pathological conditions.

PMID- 17224653
TI  - Interaction of immobilized human exportin-t with calf liver tRNA.
AB  - The binding of tRNA species from calf liver to immobilized exportin-t in the
      presence of ran x GppNHp was examined by affinity chromatography. We observed
      different eluting behaviors of individual tRNAs. After separating tRNAs on a two
      dimensional polyacrylamide gel, the positions of seven selected tRNAs were
      identified by Northern hybridization and their relative affinities to immobilized
      exportin-t x ran x GppNHp complex were estimated in the order of tRNA(Leu)(CAG) >
      tRNA(Ser)(GCU), tRNA(Leu)(CAA), tRNA(Ser)(UGA) > tRNA(Ser)(AGA), tRNA(Leu)(AAG) >
      tRNA(Arg)(ACG). We propose that exportin-t preferentially binds and exports those
      tRNAs that are rapidly consumed by the protein synthesis machinery.

PMID- 17224655
TI  - Myelodysplastic and myeloproliferative disorders in children.
AB  - PURPOSE OF REVIEW: Myelodysplastic and myeloproliferative disorders are clonal
      myeloid malignancies characterized by the triad of a growth advantage of clonal
      cells, disturbed differentiation and increased apoptosis. The rarity of these
      disorders in children and the lack of a widely accepted classification have
      contributed to the paucity of reports on these malignancies in the pediatric
      literature. A number of significant advances have been achieved in recent years.
      The present review will focus on diagnostics and therapy. RECENT FINDINGS:
      International consensus has been achieved on classifying these disorders into
      three main groups; myelodysplastic syndrome (MDS), myeloid leukemia of Down
      syndrome (ML-DS) and juvenile myelomonocytic leukemia (JMML). In the last few
      years we have witnessed important advances, especially regarding the therapy of
      these disorders, and we have gained insights into the molecular pathogenesis of
      ML-DS and JMML. SUMMARY: Classification of myelodysplastic and myeloproliferative
      disorders has been facilitated. Chemotherapy regimens for ML-DS have been
      reduced, resulting in fewer toxic deaths and improved survival. The results of
      stem-cell transplantation for MDS and JMML have improved. Insight into the
      molecular mechanisms involved may open new therapeutic avenues.

PMID- 17224656
TI  - Molecular insights into Down syndrome-associated leukemia.
AB  - PURPOSE OF REVIEW: Four years ago it was discovered that nearly all cases of
      transient myeloproliferative disorder and acute megakaryocytic leukemia in
      children with Down syndrome acquire mutations in the hematopoietic transcription
      factor gene GATA1. Studies within the past year, described within this review,
      have provided tremendous insights into the role of GATA1 mutations in these
      malignancies. RECENT FINDINGS: In the past year, our understanding of the
      molecular and cellular consequences of GATA1 mutations has been greatly enhanced.
      Most importantly, we have learned that these mutations, which result in the
      exclusive production of the short GATA1 isoform named GATA1s, have a distinct
      effect on fetal liver progenitors. In addition, multiple studies have shown that
      GATA1s can substitute for GATA1 in many aspects of megakaryocytic maturation.
      Finally, an important clinical study has revealed that GATA1 mutations alone are
      insufficient for leukemia. SUMMARY: Leukemia in children with Down syndrome
      requires at least three cooperating events--trisomy 21, a GATA1 mutation, and a
      third, as yet undefined, genetic alteration. Recent studies have provided
      tremendous insights into the GATA1 side of the story. Future experiments with
      human patient samples and mouse models will likely increase our awareness of the
      role of trisomy 21 in transient myeloproliferative disorder and acute
      megakaryocytic leukemia.

PMID- 17224657
TI  - Pharmacogenomics in cancer treatment defining genetic bases for inter-individual
      differences in responses to chemotherapy.
AB  - PURPOSE OF REVIEW: Pharmacogenomics is evolving rapidly due to the expansion of
      genomics and proteomics, the emerging technologies, knowledge of the molecular
      basis of neoplasms and of drug pathways. This article will give an update on the
      genetic basis of variable therapeutic responses to anticancer agents in children.
      RECENT FINDINGS: The majority of recent findings concern the pharmacogenetics of
      key components of acute lymphoblastic leukemia treatment, 6-mercaptopurine and
      methotrexate. This is not surprising given that leukemia is the most common
      cancer affecting children, accounting for 25-35% of childhood malignancies
      worldwide with acute lymphoblastic leukemia comprising 80% of leukemia cases. In
      certain patients treatment fails due to drug resistance, rendering acute
      lymphoblastic leukemia the leading cause of cancer-related death in children.
      Most of the studies use a candidate gene approach adding a new body of evidence
      to existing knowledge. Recent findings relating to other childhood tumors and the
      potential to optimize treatment of these malignancies are briefly discussed.
      SUMMARY: Interindividual differences in drug responses are an important cause of
      resistance to treatment and adverse drug reactions. Pharmacogenetics tends to
      identify the genetic basis of these suboptimal responses allowing traditional
      treatment to be complemented by genotype-based drug dose adjustment.

PMID- 17224658
TI  - Long-term effects of treatments for childhood cancers.
AB  - PURPOSE OF REVIEW: The late effects of current treatments for childhood cancer
      increase the risk of morbidity and mortality and diminish the quality of life in
      long-term survivors. We selectively review the negative late cardiac, endocrine,
      and neurological effects of childhood cancer and its treatments and comment on
      current research and recommendations for the care of long-term survivors of
      childhood cancer. RECENT FINDINGS: Progressive cardiotoxicity has been
      established. Late cardiac effects can be mitigated with the concomitant use of
      dexrazoxane with anthracycline. When radiotherapy is used multiple organ systems
      must be monitored for known late effects dependent on the location. Proper diet,
      physical activity, and obesity are topics that must be addressed in survivors.
      Late neurocognitive effects impact intelligence quotient, behavior, and
      achievement. Systematic follow-up with appropriate clinical screening and testing
      is important in diagnosing and potentially preventing late effects of cancer
      therapy. SUMMARY: The new paradigm for defining successful cancer therapy is the
      balance between oncologic efficacy and toxicity/late effects. The complexity of
      late effects necessitates a multidisciplinary approach to long-term care of these
      patients. The high frequency, delayed onset, and potential severity of late
      effects demand increased and lifelong monitoring of these individuals.

PMID- 17224659
TI  - Advances in understanding etiology of achondroplasia and review of management.
AB  - PURPOSE OF REVIEW: A summary of management and current research in achondroplasia
      (OMIM 100800). The most common nonlethal skeletal dysplasia, achondroplasia
      presents a distinct clinical picture evident at birth. Substantial information is
      available concerning the natural history of this dwarfing disorder. Diagnosis is
      made by clinical findings and radiographic features. Characteristic features
      include short limbs, a relatively large head with frontal bossing and midface
      hypoplasia, trident hands, muscular hypotonia, and thoracolumbar kyphosis.
      Children commonly have recurrent ear infections, delayed motor milestones, and
      eventually develop bowed legs and lumbar lordosis. People with achondroplasia are
      generally of normal intelligence. RECENT FINDINGS: The genetic cause of
      achondroplasia was discovered in 1994. Subsequent research efforts are designed
      to better characterize the underlying possible biochemical mechanisms responsible
      for the clinical findings of achondroplasia as well as to develop possible new
      therapies and/or improve intervention. SUMMARY: Establishing a diagnosis of
      achondroplasia allows families and clinicians to provide anticipatory care for
      affected children. Although the primary features of achondroplasia affect the
      skeleton, a multidisciplinary approach to care for children with achondroplasia
      helps families and clinicians understand the clinical findings and the natural
      history of achondroplasia in order to improve the outcome for each patient.

PMID- 17224660
TI  - The role of gait analysis in the orthopaedic management of ambulatory cerebral
      palsy.
AB  - PURPOSE OF REVIEW: The literature was reviewed to describe the role of gait
      analysis in the orthopaedic management of ambulatory children with cerebral palsy
      and examine the current best evidence to support these roles. RECENT FINDINGS:
      Gait laboratory analysis is superior to visual or observational analysis of gait
      because it provides an objective record of gait that is able to quantify the
      magnitude of deviations of pathologic gait from normal and also explain these
      abnormalities. Recognizable gait patterns can be classified and used for making
      treatment decisions, the effectiveness of which can be assessed using gait
      analysis as a measure of gait outcomes. There are many sources of variability,
      however, including patients themselves, the gait laboratories and testing
      processes, interpretation of data and surgeons' surgical recommendations.
      SUMMARY: Although gait analysis has been shown to alter decision making, there is
      little evidence that the decisions based on gait analysis lead to better
      outcomes. Consequently, clinical gait analysis remains controversial, with wide
      variation in the rates of utilization of gait analysis in the management of
      children with ambulatory cerebral palsy. The time is ripe for clinical trials and
      cohort studies to provide the evidence to establish the appropriate utilization
      of this technology.

PMID- 17224661
TI  - Osgood Schlatter syndrome.
AB  - PURPOSE OF REVIEW: Osgood Schlatter syndrome presents in growing children (boys,
      12-15 years; girls, 8-12 years) with local pain, swelling and tenderness over the
      tibial tuberosity. Symptoms are exacerbated with sporting activities that involve
      jumping (basketball, volleyball, running) and/or on direct contact (e.g.
      kneeling). With increased participation of adolescent children in sports, we
      critically looked at the current literature to provide the best diagnostic and
      treatment guidelines. RECENT FINDINGS: Osgood Schlatter syndrome is a traction
      apophysitis of the tibial tubercle due to repetitive strain on the secondary
      ossification center of the tibial tuberosity. Radiographic changes include
      irregularity of apophysis with separation from the tibial tuberosity in early
      stages and fragmentation in the later stages. About 90% of patients respond well
      to nonoperative treatment that includes rest, icing, activity modification and
      rehabilitation exercises. In rare cases surgical excision of the ossicle and/or
      free cartilaginous material may give good results in skeletally mature patients,
      who remain symptomatic despite conservative measures. SUMMARY: Osgood Schlatter
      syndrome runs a self-limiting course, and usually complete recovery is expected
      with closure of the tibial growth plate. Overall prognosis for Osgood Schlatter
      syndrome is good, except for some discomfort in kneeling and activity restriction
      in a few cases.

PMID- 17224662
TI  - Advances in the surgical management of pediatric femoral shaft fractures.
AB  - PURPOSE OF REVIEW: To provide an update on surgical methods of pediatric femur
      fracture treatment. RECENT FINDINGS: Multiple studies describe successful results
      with elastic nail stabilization of pediatric femur fractures. The indications and
      risk factors for complications are being more clearly defined. Trochanteric entry
      locked intramedullary nailing and submuscular bridge plating have also recently
      been reported to produce excellent outcomes in a high percentage of patients.
      Older (>11 years) patients, heavier patients and patients with length-unstable
      fracture patterns may be best treated with locked nailing or plating. SUMMARY:
      Pediatric femur fractures can be successfully treated by a number of methods.
      This review examines the recent literature to provide some guidelines for
      choosing amongst the options for surgical stabilization.

PMID- 17224663
TI  - Influenza vaccines: a pediatric perspective.
AB  - PURPOSE OF REVIEW: To understand the burden of disease attributable to influenza
      among children and to understand the basis for changing recommendations for
      immunization of young children. I will review the current recommendations
      regarding use of trivalent, inactivated influenza vaccine and live, attenuated
      influenza vaccine. RECENT FINDINGS: Annual immunization of all children between 6
      and 59 months of age and their household contacts is recommended starting with
      the 2006-2007 season, including a two-dose strategy for children under 9 years of
      age. SUMMARY: Expanded recommendations are expected to reduce the number of
      outpatient visits, hospitalization rates and mortality rates due to influenza for
      both children and adults.

PMID- 17224664
TI  - Preparing for avian influenza.
AB  - PURPOSE OF REVIEW: Pandemic influenza is inevitable, will have significant impact
      on the population and will challenge healthcare delivery. Planning for an
      influenza pandemic will improve the ability of healthcare facilities to respond
      successfully. RECENT FINDINGS: Planning activities involve determining the role
      of the facility during an influenza pandemic, estimating resources necessary to
      fulfil this role and developing the infrastructure, material and human resources
      surge capacity necessary to meet the estimated needs. Plans to perform
      surveillance for potentially contagious individuals, handle clinical specimens,
      increase social distancing during a pandemic and the development of personal
      preparedness plans may be beneficial. SUMMARY: The goal of this review is to
      provide a framework for healthcare facility pandemic influenza planning.

PMID- 17224665
TI  - New developments in the search for the etiologic agent of Kawasaki disease.
AB  - PURPOSE OF REVIEW: The aim of this article is to review recent developments in
      the search for the etiologic agent of Kawasaki disease. RECENT FINDINGS: Two
      recently proposed theories of Kawasaki disease etiology, the toxic shock syndrome
      toxin-1 hypothesis and the coronavirus NL-63 hypothesis, have been studied
      extensively and have been disproven. Surprisingly, IgA plasma cells infiltrate
      inflamed tissues in acute Kawasaki disease, including the coronary artery, and
      are oligoclonal, or antigen-driven. Synthetic versions of predominant IgA
      antibodies in acute Kawasaki disease arterial tissue bind to an antigen present
      in acute Kawasaki disease ciliated bronchial epithelium and in a subset of
      macrophages in acute inflamed Kawasaki disease tissues. Light and electron
      microscopic studies of the antigen in acute Kawasaki disease ciliated bronchial
      epithelium indicate that the Kawasaki disease-associated antigen localizes to
      cytoplasmic inclusion bodies that are consistent with aggregates of viral protein
      and associated nucleic acid. SUMMARY: The identification of cytoplasmic inclusion
      bodies in acute Kawasaki disease ciliated bronchial epithelium has provided
      direction for future Kawasaki disease etiology studies. Transmission electron
      microscopic examination of glutaraldehyde-fixed medium-sized bronchi from acute
      Kawasaki disease fatalities and analysis of the protein and nucleic acid
      components of the inclusions should provide important information about these
      inclusion bodies and speed the identification of the specific etiologic agent of
      Kawasaki disease.

PMID- 17224666
TI  - Pediatric community-acquired methicillin-resistant Staphylococcus aureus
      infection and colonization: trends and management.
AB  - PURPOSE OF REVIEW: The scourge of community-acquired methicillin-resistant
      Staphylococcus aureus in pediatrics continues unabated. This review provides
      information on changes in epidemiology, therapeutic considerations, and measures
      to control the epidemic. RECENT FINDINGS: The epidemiology and clinical
      manifestations of methicillin-resistant S. aureus have undergone important
      changes that pose challenges in recognition, diagnosis, and treatment for the
      pediatrician. Community-acquired methicillin-resistant S. aureus used to be
      predominantly associated with localized disease among previously healthy
      children; however, there are recent reports of more invasive and severe diseases
      with some fatalities. The antibiotic susceptibility pattern is also changing with
      some community-acquired methicillin-resistant S. aureus having resistance
      patterns indistinguishable from that of hospital-acquired methicillin-resistant
      S. aureus. Thus the choice of antibiotics is becoming even more challenging in
      pediatrics, with an already-limited armamentarium of antibiotics. The management
      of common skin diseases such as furunculosis and boils now requires close
      collaboration between the general pediatrician and the infectious diseases
      specialist. SUMMARY: As the burden of community-acquired methicillin-resistant S.
      aureus disease continues to increase, pediatricians must have a high index of
      suspicion and must institute appropriate antimicrobial therapy based on community
      or regional antibiotic susceptibility of community-acquired methicillin-resistant
      S. aureus. There is an urgent need for effective infection control programs,
      including active surveillance components, to help curb the epidemic.

PMID- 17224667
TI  - Pseudomonas aeruginosa chronic colonization in cystic fibrosis patients.
AB  - PURPOSE OF REVIEW: Chronic infection with Pseudomonas aeruginosa is a leading
      cause of morbidity and mortality in individuals with cystic fibrosis despite the
      aggressive use of antibiotics. P. aeruginosa employs a number of strategies that
      promote chronic pulmonary colonization instead of acute infection. These include
      biofilm formation, evasion of the host immune system, and conversion to a mucoid
      phenotype. This review discusses recent advances regarding P. aeruginosa
      pathogenesis and biofilm behavior in the setting of chronic pulmonary disease.
      RECENT FINDINGS: Biofilm formation in the cystic fibrosis lung likely occurs
      under anaerobic conditions, is controlled by bacterial quorum-sensing mechanisms,
      and is enhanced by environmental components in the cystic fibrosis airway. P.
      aeruginosa possesses regulatory pathways that recognize environmental cues to
      favor either acute infection or chronic colonization. P. aeruginosa that inhabit
      the respiratory tract accumulate mutations favoring chronic colonization.
      Azithromycin, a macrolide with clinical benefit in cystic fibrosis, alters P.
      aeruginosa biofilm formation. Promising new therapies that target biofilm
      formation include molecules that disrupt quorum sensing. SUMMARY: Eradication of
      P. aeruginosa in cystic fibrosis patients remains problematic. As more
      information emerges about P. aeruginosa behavior in vivo, potential therapeutics
      directed against biofilms and mucoid P. aeruginosa are being developed.

PMID- 17224668
TI  - Skin barrier function in atopic dermatitis.
AB  - PURPOSE OF REVIEW: Whereas much investigation in atopic dermatitis has focused
      upon the adaptive immune response, new data suggest that allergic sensitization
      may occur secondary to impairment of skin barrier function. RECENT FINDINGS: Two
      common loss-of-function mutations in the FLG gene encoding filaggrin (an
      important component of terminal keratinocyte differentiation) are strongly
      associated with the development of atopic dermatitis and asthma associated with
      atopic dermatitis. SUMMARY: Genetic defects in skin barrier function should be
      recognized as major risk factors for the development of atopic dermatitis and
      asthma.

PMID- 17224669
TI  - Update on epinephrine for the treatment of anaphylaxis.
AB  - PURPOSE OF REVIEW: Epinephrine is the treatment of choice for anaphylaxis--a life
      threatening and potentially fatal event. The purpose of this review is to
      highlight recent publications relevant to the management of anaphylaxis and
      identify potential barriers which prevent or delay appropriate administration of
      epinephrine. RECENT FINDINGS: Experts have moved towards a consensus on how to
      define anaphylaxis, which has a variable clinical presentation. A clear
      definition, across specialties, is necessary for more accurate determinations of
      prevalence, diagnosis and management. Epinephrine injected intramuscularly is the
      treatment of choice, but there remain gaps in physician knowledge despite
      increases in hospitalization rates for anaphylaxis. Epinephrine is also underused
      by parents, day-care centers and schools. Barriers to access for treatment exist
      in lower socioeconomic groups. Women appear to be at risk for suboptimal
      treatment when autoinjectors are used. Given these issues, other routes of
      administration of epinephrine have been explored. Epinephrine delivered via a
      sublingual route has been successful in animal studies. SUMMARY: Epinephrine is
      the primary therapy for anaphylaxis, yet studies show that it is underutilized.
      By addressing the contributory factors that have been identified, acute and long
      term care of individuals with this potentially life-threatening disorder can be
      optimized.

PMID- 17224670
TI  - Promotion of physical activity in primary care for obesity treatment/prevention
      in children.
AB  - PURPOSE OF REVIEW: Physical activity has been highlighted internationally as a
      beneficial intervention for weight control and the improvement of physical and
      mental health. This review highlights findings from recent literature to guide
      office-based promotion of physical activity for obesity treatment and prevention.
      RECENT FINDINGS: Children worldwide participate in far less than the current
      physical activity recommendations. Family-based activity provides children with
      positive role modeling as well as motivational support for maintaining an active
      lifestyle. The integration of physical activity into daily life can be an
      effective alternative to sports and structured exercise programs. Decreasing
      sedentary behaviors is also a positive contribution, although its link to
      physical activity levels is still unclear. Some families may see neighborhood
      safety and access to recreational facilities as barriers to keeping their
      children physically active. SUMMARY: Research in the field of pediatric obesity
      and overweight treatment and prevention continues to find challenges and
      solutions. Promotion of physical activity by the pediatric provider is
      demonstrated by current evidence to be a positive intervention against this
      global problem.

PMID- 17224671
TI  - Bibliography. Current world literature. Hematology and oncology.

PMID- 17224672
TI  - Updates in Acanthamoeba keratitis.
AB  - PURPOSE: Acanthamoeba keratitis is a potentially blinding microbial disease that
      has been increasing in incidence during the past two decades. Prognosis of this
      serious disease had been dismal, but improvement in diagnosis, a better
      understanding of the natural course of the disease, and recent introduction of
      multiple and effective therapeutic agents have resulted in improvement of visual
      outcomes. METHODS: A review of literature pertaining to Acanthamoeba keratitis.
      RESULTS: Contact lens wear and exposure to contaminated water sources remain the
      most important risk factors; however, in vivo confocal microscopy and improved
      biomicroscopic screening have proven instrumental in accurate early diagnosis.
      Complications of Acanthamoeba keratitis include dacryoadenitis, corneal melting
      and scarring, severe secondary glaucoma, cataract, and chronic anterior segment
      inflammation that can rarely lead to reactive blinding retinal ischemia.
      Combination chemotherapeutic agents have been shown to be more effective than
      monotherapy, whereas rehabilitative surgery such as penetrating keratoplasty is
      best performed on a quiet eye free of ocular inflammation and with no residual
      amoebae. CONCLUSIONS: Increased suspicion by clinicians for Acanthamoeba and
      confocal microscopy have allowed more rapid and accurate diagnosis; treatment
      with multiple antiamoeba drugs is essential to disease resolution. Provided there
      are no residual amoebae after treatment, penetrating keratoplasty has been
      successful in visual rehabilitation. Secondary glaucoma occurs frequently and may
      require drainage procedures for control of intraocular pressure. Posterior
      complications are rare but may lead to ischemic retinitis.

PMID- 17224673
TI  - A scleral soft contact lens designed for the postoperative management of
      pterygium surgery.
AB  - PURPOSE: To introduce a new hydrophilic contact lens design to be used as a
      corneoscleral bandage for different types of conjunctival surgery and pterygium
      surgery. METHODS: The soft lenses are fabricated in large diameters from 17.5 to
      19 mm and have custom peripheral curvatures to guarantee a normal tear film
      circulation to allow for extended wear for 2 or 3 consecutive weeks. CONCLUSIONS:
      This novel design facilitates postoperative recovery and reduces the chance of
      recurrence after pterygium surgery. The authors have been using this type of lens
      in their clinical practice for more than 4 years.

PMID- 17224674
TI  - Modern scleral lenses part I: clinical features.
AB  - PURPOSE: To evaluate the indications for modern scleral lenses and their clinical
      performance in patients who were fitted with scleral lenses at the authors'
      practices. METHODS: In this cross-sectional survey, all the necessary data were
      obtained at the first follow-up visit during the 5-month study period. There were
      four types of scleral lenses: spherical, front-surface toric, back-surface toric,
      and bitoric. The preformed scleral lens fitting technique developed at Visser
      Contact Lens Practice was used in all patients. The lenses were cut by precise
      Sub Micron Lathing from a Boston Equalens II blank at Procornea. Visual acuity
      and slitlamp findings were recorded. A specially designed classification for
      scleral lens fitting was used to investigate clinical performance. RESULTS: The
      largest proportion of the 178 patients (284 eyes) were diagnosed with keratoconus
      (143 [50.4%] eyes) followed by postpenetrating keratoplasty (56 [19.7%] eyes).
      The remaining diagnoses were irregular astigmatism, keratitis sicca, corneal
      dystrophy, and multiple diagnoses. The ratio of spherical to back-surface toric
      designs was 1:1.1. Clinical examination showed sharp increases in visual acuity
      (median increase, 0.45) and safe physiologic responses of the anterior eye. All
      the patients could continue to wear scleral lenses, with 79.2% with the same lens
      parameters. CONCLUSIONS: Several types of corneal abnormality were managed
      successfully with modern scleral lenses. The main indication was optical
      correction of an irregular corneal surface. Satisfactory clinical performance
      meant that all the patients could continue to wear their scleral lenses.

PMID- 17224675
TI  - Modern scleral lenses part II: patient satisfaction.
AB  - PURPOSE: To evaluate the subjective performance of modern scleral lenses in
      patients of the clinics of Visser Contact Lens Practice. METHODS: In this cross
      sectional survey, all the necessary data were collected at the first follow-up
      visit during the 5-month study period. In accordance with the preformed fitting
      technique developed at Visser Contact Lens Practice, four types of scleral lenses
      were used: spherical, front-surface toric, back-surface toric, and bitoric.
      Subjective performance was investigated during an interview that included the use
      of a five-point Likert scale and by means of a questionnaire supplemented by a
      100-mm visual analog scale (VAS). RESULTS: The interview and questionnaire showed
      high scores for patient satisfaction with the current scleral lens in the 178
      patients (284 eyes) (median score, 4; range Likert scale, 1-5; median score,
      >or=75; range VAS, 1-100). Significant increases in scores were seen with the
      current scleral lens compared to the former correction: 78.9% for comfort, 78.2%
      for visual quality, and 87.7% for overall satisfaction (n=284 eyes) (P<0.001). In
      the 99 eyes that switched from back-surface spherical to back-surface toric
      designs, the following significant increases were seen: 61.6%, 37.4%, and 65.7%,
      respectively (P<0.001). CONCLUSIONS.: High patient satisfaction was seen with all
      the modern scleral lens designs in the management of several forms of corneal
      abnormality. The interview showed differences in comfort, visual quality, and
      overall satisfaction in favor of the back-surface toric designs compared to the
      back-surface spherical designs.

PMID- 17224676
TI  - In vitro assessment of medical device toxicity: interactions of benzalkonium
      chloride with silicone-containing and p-hema-containing hydrogel contact lens
      materials.
AB  - PURPOSE: To analyze the interactions of benzalkonium chloride (BAK) with silicone
      containing (lotrafilcon A and galyfilcon A) and p-HEMA-containing (etafilcon A
      and vifilcon A) hydrogel contact lenses and to examine the possibility of using
      sodium fluorescein permeability assay (SFPA), 3-(4,5-dimethylthiazol- 2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay and the bovine lens assay in conjunction
      with confocal laser scanning microscopy (CLSM) as a battery of in vitro
      alternatives to evaluate the potential toxicity of soft contact lenses. METHODS:
      Four soft contact lens types (Focus Monthly [vifilcon A], Focus NIGHT & DAY
      [lotrafilcon A], ACUVUE Advance With Hydraclear [galyfilcon A], and SUREVUE
      [etafilcon A]) were soaked for 24 hours in various concentrations of BAK (1%,
      0.1%, 0.01%, and 0.001%) in 20-mL glass vials. After 24 hours, the lenses were
      gently washed in Hanks' Balanced Salt Solution (HBSS), placed in 5 mL of HBSS,
      and incubated for a total of 7 days at 37 degrees C, 5% CO2. BAK released into
      HBSS (i.e., the extract) was recovered from the vials and used as the test
      chemical in the SFPA (epithelium integrity), MTT assay (cellular viability), and
      the bovine lens assay with CLSM (mitochondrial metabolism and optical
      properties). The amount of BAK extracted from the various contact lenses was
      measured using an Abbe refractometer. Negative controls consisted of HBSS and
      contact lenses subjected to the same conditions as the treated contact lenses,
      but without BAK. RESULTS: Extracts obtained from soaking Focus Monthly lenses in
      BAK caused the most damage to the epithelium and mitochondrial metabolism.
      However, at 0.1% BAK extraction, all lens extracts showed increased levels of
      back vertex distance variability of the cultured bovine lens. CONCLUSIONS:
      Unexpectedly, lenses extracted with HBSS showed SFPA and MTT assay responses and
      an observed effect on the bovine lens epithelium visualized by CLSM, indicating
      that unknown chemical agents may be leached from contact lens polymers.

PMID- 17224677
TI  - Comparison of the efficacy of two lipid emulsion eyedrops in increasing tear film
      lipid layer thickness.
AB  - PURPOSE: The lipid layer of the tear film is critical to maintaining the
      thickness of the multilayered tear film. This study was designed to determine
      whether a single drop of Refresh Dry Eye Therapy or Soothe, both lipid emulsion
      eyedrops, significantly increased the lipid layer thickness (LLT) of patients
      with self-reported dry eyes and thin lipid layers. METHODS: Lipid layer
      interference patterns were used to quantify the LLT of both eyes of eligible
      patients before and after test drop instillation. Patients (n=41) reporting dry
      eye symptoms and having baseline LLT of no more than 75 nm received 40 microL of
      Refresh Dry Eye Therapy in one eye and 40 microL of Soothe in the contralateral
      eye. After instillation, LLT was quantified at 1, 5, and 15 minutes. LLT after
      drop instillation was averaged for the three time points. RESULTS: The mean +/-
      standard error baseline LLT was 59.6 +/- 1.7 nm for eyes treated with Refresh Dry
      Eye Therapy and 61.5 +/- 1.6 nm for eyes treated with Soothe. These means were
      not significantly different (P>0.05). The overall mean LLT after drop
      instillation was 83.2 +/- 3.6 nm for Refresh Dry Eye Therapy (P<0.0001) and 121.5
      +/- 3.8 nm for Soothe (P<0.0001). The mean LLT increase from Soothe (60.0 nm) was
      significantly greater than that from Refresh Dry Eye Therapy (23.6 nm)
      (P<0.0001). CONCLUSIONS: The application of a lipid emulsion eyedrop will
      increase LLT and benefit patients with deficient lipid layers who experience dry
      eye symptoms. Although both products are lipid emulsions, one drop of Soothe
      essentially doubled LLT and provided a mean increase in LLT that was 2.5 times
      greater than that of Refresh Dry Eye Therapy.

PMID- 17224678
TI  - Microbial keratitis pathogens and antibiotic susceptibilities: a 5-year review of
      cases at an urban county hospital in north Texas.
AB  - PURPOSE: To review the epidemiology, risk factors, microbiologic spectrum, and
      outcomes of microbial keratitis and to compare cases in which a causative
      organism is identified to those determined to be sterile during a 5-year period
      at a large county hospital in north Texas. METHODS: A retrospective chart review
      of cases of microbial keratitis at Parkland Memorial Hospital between January
      2000 and December 2004. RESULTS: During this 5-year period, 132 eyes of 131
      patients underwent 139 corneal scrapings for presumed microbial keratitis and an
      organism was reported in 73 (52.5%) cultures. Including abnormal confocal
      microscopy results, a causative organism was determined in 78 (56.1%) cases. At
      least one risk factor was present in 115 (87.1%) cases, with the most common risk
      factors being preexisting ocular disease, contact lens wear, and a history of
      trauma. Nearly 5% of patients reported a history of cocaine use. Gram staining
      correctly identified the organism in 20 (28.6%) culture-positive cases, and
      Pseudomonas aeruginosa was the most common isolate, followed by Staphylococcus
      aureus. The rate of S. aureus resistance to fluoroquinolones (15.4%) was similar
      to rates previously reported from the early to mid 1990s, but less than those
      reported from the late 1990s. Severe complications were more common in the
      nonsterile subgroup (34.2%) than in the sterile (16.9%) subgroup (P=0.041).
      Although the rate of acute intervention was higher in the nonsterile subgroup
      (27.4%) than in the sterile subgroup (20.3%), this difference was not
      statistically significant (P=0.461). Mean logMAR visual acuity was 1.451 (Snellen
      equivalent, 20/563) at presentation and 1.062 (20/231) at the last follow-up
      visit (P<0.001). Presenting and final visual acuities were significantly better
      in the sterile subgroup than in the nonsterile subgroup (P<0.001 and P=0.002,
      respectively). CONCLUSIONS: When a causative organism is not identified in
      microbial keratitis, visual acuity is not as severely affected, and fewer severe
      complications occur. Antibiotic resistance to fluoroquinolones and
      aminoglycosides, though not common, still deserves consideration in the treatment
      of microbial keratitis.

PMID- 17224679
TI  - Paragon corneal refractive therapy lens prescribed for daily wear in a post
      radial keratometry patient.
AB  - PURPOSE: To present a case in which the Corneal Refractive Therapy (CRT) lens, a
      reverse-geometry contact lens designed specifically for overnight
      orthokeratology, was prescribed for daily wear in the treatment of a patient
      after radial keratotomy. METHODS: Case report. RESULTS: The CRT lens provided
      adequate visual acuity and satisfactory daily wearing time without an adverse
      physiologic response. CONCLUSIONS: This case illustrates an off-label use of the
      CRT lens to facilitate lens centration and provide a functional vision correction
      that enhanced a patient's ability to participate in activities of daily living.
      Although further study regarding the long-term safety and efficacy of this lens
      modality is needed, the findings suggest that these lenses provide a viable
      vision correction for patients who are dissatisfied with their postsurgical
      vision, particularly when satisfactory visual acuity cannot be achieved through
      conventional means.

PMID- 17224680
TI  - Clinical investigation of two contact lens care products and their relationship
      to corneal sensitivity, comfort and corneal staining.

PMID- 17224681
TI  - Recent Fusarium outbreak.

PMID- 17224683
TI  - A future for medical genetics: lessons from Catch 22.

PMID- 17224684
TI  - Association study between the NMDA receptor 2B subunit gene (GRIN2B) and
      schizophrenia: a HuGE review and meta-analysis.
AB  - Schizophrenia is a severe mental illness to which hypofunction of the N-methyl-D
      aspartate receptors has been linked. Association studies have implicated the N
      methyl-D-aspartate receptor 2B subunit gene (GRIN2B) as a candidate for
      schizophrenia. Subsequent studies have attempted to replicate the association,
      but the results have been mixed and thus inconclusive. It is necessary to explain
      the inconsistency of these results and to clarify the contribution of the GRIN2B
      gene to schizophrenia. The current meta-analysis covers all published association
      studies up to January 2006 using systematic allelic and genotypic analyses
      involving five polymorphisms. The results show evidence of a statistically
      significant association for GRIN2B. The association seems weaker, but nonetheless
      interesting. The meta-analysis supports the involvement of the glutamate system
      of the brain in the pathogenesis of schizophrenia. This may be the first
      systematic meta-analysis study focusing on GRIN2B.

PMID- 17224685
TI  - APOE is a potential modifier gene in an autosomal dominant form of frontotemporal
      dementia (IBMPFD).
AB  - PURPOSE: Inclusion-body myopathy, Paget's disease of bone and frontotemporal
      dementia is an adult-onset autosomal dominant illness (IBMPFD) caused by
      mutations in the valosin-containing protein (VCP) on chromosome 9p21.1-p12. The
      penetrance of the gene is 82% for myopathy, 49% for Paget's disease, but may be
      as low as 30% for frontotemporal dementia. Modifier genes could account for
      decreased frontotemporal dementia penetrance. In this study apolipoprotein-E
      (APOE) was evaluated for this role in IBMPFD families based on its known modifier
      effect in Alzheimer's disease. METHODS: From a database of 231 members of 15
      families, 174 had APOE genotype available for analysis. Logistic regressions on
      APOE genotype and frontotemporal dementia were performed, using appropriate
      covariates. RESULTS AND CONCLUSION: FTD was associated with APOE 4 genotype
      (P=0.0002), myopathy (P=0.0006), and age (P=0.01), but not microtubule associated
      protein tau (MAPT) H2 haplotype (P=0.5) or gender (0.09) after adjustment for
      membership in pedigrees with at least one APOE 4 genotype. These data suggest a
      potential link between APOE 4 genotype and the specific form of frontotemporal
      dementia found in IBMPFD. The molecular basis of this link bears further
      investigation. We did not observe an association of frontotemporal dementia and
      H2 MAPT haplotype.

PMID- 17224686
TI  - Genotype-phenotype correlations in hereditary hemorrhagic telangiectasia: data
      from the French-Italian HHT network.
AB  - PURPOSE: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder
      characterized by arteriovenous malformations (AVM), mostly cutaneous and mucous
      (telangiectases), but also involving the lungs (PAVM), liver (HAVM) and brain
      (CAVM). We studied the relationship between the phenotype and genotype in
      patients with a proven mutation in either ENG (HHT1) or ACVRL1 (HHT2). METHODS:
      Clinical features and their age of onset were compared between HHT1 and HHT2. The
      type of mutation was also analyzed. Clinical manifestations were distinguished
      from lesions found by screening. RESULTS: Ninety-three HHT1 patients and 250 HHT2
      patients were included. Epistaxis occurred later in HHT2, with incomplete
      penetrance (P<0.0001). Symptomatic PAVMs were more frequent in HHT1 (34.4 vs.
      5.2%, P<0.001), as were cerebral abscesses (7.5 vs. 0.8%, P=0.002).
      Gastrointestinal bleeding occurred more frequently in HHT2 (16.4 vs. 6.5%,
      P=0.017). Symptomatic hepatic involvement was only seen in HHT2 patients. PAVMs
      were more frequently detected in asymptomatic HHT1 patients (54 vs. 12.8%,
      P<0.0001). PAVMs and HAVMs were often family clustered in HHT1 and HHT2,
      respectively. Truncating mutations were associated with a higher frequency of
      epistaxis and telangiectasis, in HHT2. CONCLUSION: This study shows major
      differences between HHT1 and HHT2 phenotypes, which should be taken into account
      for future clinical studies.

PMID- 17224687
TI  - Whole blood RNA offers a rapid, comprehensive approach to genetic diagnosis of
      cardiovascular diseases.
AB  - PURPOSE: Long QT Syndrome, Marfan Syndrome, hypertrophic and dilated
      cardiomyopathy are caused by mutations in large, multi-exon genes that are
      principally expressed in cardiovascular tissues. Genetic testing for these
      disorders is labor-intensive and expensive. We sought to develop a more rapid,
      comprehensive, and cost-effective approach. METHODS: Paired whole blood samples
      were collected into tubes with or without an RNA-preserving solution, and
      harvested for whole blood RNA or leukocyte DNA, respectively. Large overlapping
      cDNA fragments from KCNQ1 and KCNH2 (Long QT Syndrome), MYBPC3 (hypertrophic and
      dilated cardiomyopathy), or FBN1 (Marfan Syndrome) were amplified from RNA and
      directly sequenced. Variants were confirmed in leukocyte DNA. RESULTS: All 4
      transcripts were amplified and sequenced from whole blood mRNA. Six known and 2
      novel mutations were first identified from RNA of 10 probands, and later
      confirmed in genomic DNA, at considerable savings in time and cost. In one
      patient with MFS, RNA sequencing directly identified a splicing mutation. Results
      from RNA and DNA were concordant for single nucleotide polymorphisms at the same
      loci. CONCLUSION: Taking advantage of new whole blood RNA stabilization methods,
      we have designed a cost-effective, comprehensive method for mutation detection
      that should significantly facilitate clinical genetic testing in four lethal
      cardiovascular disorders.

PMID- 17224688
TI  - Heterozygous Fabry women are not just carriers, but have a significant burden of
      disease and impaired quality of life.
AB  - PURPOSE: To determine if there is significant symptomatology in women with
      heterozygous alpha-galactosidase mutations. METHODS: Data from medical records of
      the 44 heterozygous females followed at Cedars-Sinai Medical Center were compiled
      and analyzed for symptoms of Fabry disease. Quality of life data were also
      analyzed. RESULTS: Seventy-six percent were referred due to an affected male
      relative; 76% reported acroparesthesias as their first symptom. A mean of 15.7
      years elapsed from onset of first symptoms to the diagnosis. Quality of life,
      measured by the SF-36 survey, was globally reduced. Pain affected mood and
      enjoyment of life. Central/peripheral nervous, cardiopulmonary, and renal system
      manifestations of Fabry disease were present far above that predicted for random
      X-inactivation of the normal allele. Fatigue, present in 59%, was associated with
      reduced maximum oxygen consumption (P=0.049); exercise intolerance, present in
      83%, was associated with reduced maximal heart rate during exercise testing
      (P=0.0089). Women diagnosed via family history experienced more angina (P=0.035),
      decreased vibration sense (P=0.026), and had a worse percentage predicted FEF25
      75 (P=0.037) compared to women diagnosed because of symptoms. CONCLUSIONS: This
      study indicates that the asymptomatic female carrier of Fabry disease is the
      exception, not the rule: heterozygotes suffer from significant multisystemic
      disease and reduced quality of life and must be monitored and treated
      accordingly.

PMID- 17224689
TI  - Molecular testing for Fragile X Syndrome: lessons learned from 119,232 tests
      performed in a clinical laboratory.
AB  - PURPOSE: To examine the data from over 119,000 Fragile X Syndrome tests and 307
      prenatal tests to detect unsuspected findings and obtain clinical data when
      indicated to optimize genetic counseling. METHODS: A proprietary database
      containing 119,232 consecutive postnatal and 307 prenatal FXS tests performed
      between November 2, 1992 and June 1, 2006 was queried. RESULTS: The distribution
      of normal FMR1 alleles was a bimodal distribution with a major peak at 30 repeats
      and a minor peak at 21 repeats. Of 59,707 tests performed for males, 1.4% had a
      fully expanded and methylated FMR1 allele. Of 59,525 tests performed for females,
      0.61% had an affected FMR1 allele, and 1.7% had a premutation FMR1 allele for a
      total carrier frequency of 1.3%. When fetuses inherited an expanded maternal
      allele, the risk of expansion to a full affected allele was 0%, 5%, 30% and 100%
      for allele sizes of <50, 50-75, 76-100 and >100 repeats, respectively.
      CONCLUSIONS: These figures can be used for genetic counseling of patients
      presenting for carrier detection and prenatal diagnosis for Fragile X Syndrome.

PMID- 17224690
TI  - X-linked infantile spinal muscular atrophy: clinical definition and molecular
      mapping.
AB  - PURPOSE: X-linked infantile spinal-muscular atrophy (XL-SMA) is a rare disorder,
      which presents with the clinical characteristics of hypotonia, areflexia, and
      multiple congenital contractures (arthrogryposis) associated with loss of
      anterior horn cells and death in infancy. We have previously reported a single
      family with XL-SMA that mapped to Xp11.3-q11.2. Here we report further clinical
      description of XL-SMA plus an additional seven unrelated (XL-SMA) families from
      North America and Europe that show linkage data consistent with the same region.
      METHODS: We first investigated linkage to the candidate disease gene region using
      microsatellite repeat markers. We further saturated the candidate disease gene
      region using polymorphic microsatellite repeat markers and single nucleotide
      polymorphisms in an effort to narrow the critical region. Two-point and
      multipoint linkage analysis was performed using the Allegro software package.
      RESULTS: Linkage analysis of all XL-SMA families displayed linkage consistent
      with the original XL-SMA region. CONCLUSION: The addition of new families and new
      markers has narrowed the disease gene interval for a XL-SMA locus between SNP
      FLJ22843 near marker DXS 8080 and SNP ARHGEF9 which is near DXS7132 (Xp11.3
      Xq11.1).

PMID- 17224692
TI  - Applying research evidence to optimize telehomecare.
AB  - Telemedicine is the use of technology to provide healthcare over a distance.
      Telehomecare, a form of telemedicine based in the patient's home, is a
      communication and clinical information system that enables the interaction of
      voice, video, and health-related data using ordinary telephone lines. Most home
      care agencies are adopting telehomecare to assist with the care of the growing
      population of chronically ill adults. This article presents a summary and
      critique of the published empirical evidence about the effects of telehomecare on
      older adult patients with chronic illness. The knowledge gained will be applied
      in a discussion regarding telehomecare optimization and areas for future
      research. The referenced literature in PubMed, MEDLINE, CDSR, ACP Journal Club,
      DARE, CCTR, and CINAHL databases was searched for the years 1995-2005 using the
      keywords "telehomecare" and "telemedicine," and limited to primary research and
      studies in English. Approximately 40 articles were reviewed. Articles were
      selected if telehealth technology with peripheral medical devices was used to
      deliver home care for adult patients with chronic illness. Studies where the
      intervention consisted of only telephone calls or did not involve video or in
      person nurse contact in the home were excluded. Nineteen studies described the
      effects of telehomecare on adult patients, chronic illness outcomes, providers,
      and costs of care. Patients and providers were accepting of the technology and it
      appears to have positive effects on chronic illness outcomes such as self
      management, rehospitalizations, and length of stay. Overall, due to savings from
      healthcare utilization and travel, telehomecare appears to reduce healthcare
      costs. Generally, studies have small sample sizes with diverse types and doses of
      telehomecare intervention for a select few chronic illnesses; most commonly heart
      failure. Very few published studies have explored the cost or quality
      implications since the change in home care reimbursement to prospective payment.
      Further research is needed to clarify how telehomecare can be used to maximize
      its benefits among diverse adult chronic illness populations.

PMID- 17224693
TI  - Simulator technology as a tool for education in cardiac care.
AB  - Assisting nurses in gaining the cognitive and psychomotor skills necessary to
      safely and effectively care for patients with cardiovascular disease can be
      challenging for educators. Ideally, nurses would have the opportunity to
      synthesize and practice these skills in a protected training environment before
      application in the dynamic clinical setting. Recently, a technology known as high
      fidelity human simulation was introduced, which permits learners to interact with
      a simulated patient. The dynamic physiologic parameters and physical assessment
      capabilities of the simulated patient provide for a realistic learning
      environment. This article describes the High Fidelity Human Simulation Laboratory
      at the University of Pittsburgh School of Nursing and presents strategies for
      using this technology as a tool in teaching complex cardiac nursing care at the
      basic and advanced practice nursing levels. The advantages and disadvantages of
      high fidelity human simulation in learning are discussed.

PMID- 17224694
TI  - Telehealth as a tool for enhancing care for patients with cardiovascular disease.
AB  - Telehealth refers to the use of telecommunication technology to remove time and
      distance barriers in the delivery of healthcare services. Telehealth can help
      nurses provide education and counseling, social support, disease monitoring, and
      disease management reminders to cardiovascular patients in their homes. As a
      result, patients gain more flexibility in scheduling healthcare visits, have
      easier and more convenient access to healthcare, may have fewer time-demanding
      clinic visits, receive care in a location that does not require the burden of
      transportation, and in an environment that is less threatening than a clinic or
      emergency department. Cardiovascular healthcare may be enhanced through diverse
      telehealth applications, including sensor technology and wearable monitoring
      systems, Internet-based peripheral monitoring devices, videophones, interactive
      voice response systems, and nanotechnology. Although telehealth enhances care,
      legal, human, and environmental factors need to be considered before implementing
      a telehealth program. Additionally, more evidence that is obtained through large
      multicenter controlled trials about the potential benefits and cost effectiveness
      of telecardiovascular health is needed.

PMID- 17224695
TI  - Use of a telehealth device to deliver a symptom management intervention to
      cardiac surgical patients.
AB  - A variety of approaches can provide cardiac patients with needed follow-up care.
      However, with the explosion of telehealth capabilities, clinicians are more ready
      to explore other methods to integrate the use of telehealth devices into the
      delivery of effective nursing interventions. This article summarizes the
      development of a symptom management intervention for coronary artery bypass graft
      patients using the Health Buddy to deliver a nursing intervention in the early
      recovery period after hospital discharge. Considerations used to design the
      symptom management intervention and selection of this telehealth modality are
      discussed. This overview can help clinicians and researchers gain perspective on
      how to evaluate telehealth modalities to aid in the delivery of interventions for
      cardiac and other clinical populations.

PMID- 17224696
TI  - Integrating telehealth as a strategy for patient management after discharge for
      cardiac surgery: results of a pilot study.
AB  - Advances in telecommunication technologies have improved access and availability
      of telehealth for use in healthcare. In cardiac care, telehealth has
      predominantly been used to manage patients with heart failure. The use of
      telehealth as a strategy for patient management after discharge for cardiac
      surgery can be beneficial in monitoring postoperative status and in the early
      detection of complications. This article provides an overview of the use of
      telehealth and telemanagement in cardiac patients and discusses the results of a
      pilot study as an example of an application of the use of telehealth for elderly
      cardiac surgery patients at high risk of postoperative complications.

PMID- 17224697
TI  - Designing and testing telehealth interventions to improve outcomes for
      cardiovascular patients.
AB  - This article presents considerations for the design and testing of electronic
      interventions to improve recovery outcomes in cardiac patients. A brief
      description of the design and testing of 2 telehealth interventions for cardiac
      patients is provided: HeartCare and E-CHANGE. The HeartCare project was a
      randomized trial of a home support program for patients after coronary artery
      bypass graft surgery. E-CHANGE is an Internet-based home support program designed
      to increase lifestyle exercise after a cardiac event. Lessons learned from these
      2 projects regarding design considerations, system use, effectiveness, and
      research challenges are discussed. Methods to promote the preservation of nursing
      values in electronic systems are described, as well nursing roles in the use of
      computer-assisted care.

PMID- 17224698
TI  - Videoconferencing and telehealth technologies can provide a reliable approach to
      remote assessment and teaching without compromising quality.
AB  - Cardiovascular disease remains a significant chronic healthcare problem in this
      country, with considerable associated economic and quality-of-life challenges.
      Along with these challenges, there is high demand for healthcare provider time,
      particularly in the areas of management of complex healthcare needs and patient
      education. At the same time, a critical nursing shortage exists. Telehealth
      technologies provide opportunities to meet the rapidly growing needs of consumers
      and healthcare practitioners. Many in need of services have limited access to
      high-end technologies. An argument has been made that the lowest level of
      technology needed to carry out a task should be used, if it is capable of
      providing the necessary services. Videoconferencing capabilities allow healthcare
      practitioners to engage in virtual face-to-face encounters with patients or other
      healthcare providers. A variety of levels of sophistication in these
      videoconferencing systems are available. In an effort to evaluate the
      effectiveness and consumer satisfaction with videoconferencing, 3 pilot studies
      were conducted to compare face-to-face, low-bandwidth, and high-bandwidth
      approaches to performing common assessments and patient education activities. In
      one study, a variety of experienced healthcare practitioners performed functional
      assessments of stroke subjects using a collection of validated scales by varying
      approaches (face-to-face, low-bandwidth, and high-bandwidth videoconferencing) in
      a randomized order. In a second study, undergraduate nursing students performed
      similar performance measures and taught an unfamiliar individual how to program
      and use an intravenous pump device, take a tympanic temperature, or to draw up
      insulin in a syringe. In the third study, advanced practice nursing students
      assessed vital signs and performed cardiopulmonary assessments on community
      dwelling subjects using low-bandwidth and face-to-face approaches. Healthcare
      practitioners and students generally preferred high-bandwidth approaches over low
      bandwidth alternatives when videoconferencing was performed; however, most
      participants and practitioners were satisfied with the encounters, regardless of
      the level of technology used.

PMID- 17224699
TI  - Maintaining hope in transition: a theoretical framework to guide interventions
      for people with heart failure.
AB  - Theoretical frameworks provide a structure for the planning and delivery of
      nursing care and for research. Heart failure (HF), a condition of increasing
      prevalence in communities internationally, is responsible for high rates of
      morbidity, mortality, and great societal burden. The HF illness trajectory can be
      unpredictable and uncertain. Markers of transition, such as functional decline
      and increasing dependence, can signal the need for transition to a more
      palliative approach. This transition challenges clinicians to deliver information
      and interventions and to support patients and their families not only in relation
      to their physical status but also in the social, psychological, and existential
      dimensions. This article describes a theoretical framework, Maintaining Hope in
      Transition, informed by transition theory, to assist patients to cope with a
      diagnosis of HF and to guide development of nursing interventions. Transition
      theory provides a useful context to assist clinicians, patients, and their
      families adjust to the challenges inherent in a diagnosis of HF and negotiating
      the illness trajectory. Key factors acknowledged in the Maintaining Hope in
      Transition framework that determine its utility in models of care for HF patients
      are (1) acknowledging the changing of life circumstances, (2) restructuring
      reality, (3) dealing with vulnerability, (4) achieving normalization, and (5)
      resolving uncertainty. It is likely that incorporation of these factors in care
      planning, information, and interventions can facilitate patients' and their
      families' abilities to negotiate the HF illness trajectory, particularly in the
      advanced stages.

PMID- 17224700
TI  - Hypertrophic cardiomyopathy: a review of etiology and treatment.
AB  - Hypertrophic cardiomyopathy (HCM) is a congenital cardiac disease with an
      estimated prevalence of 1:500 in the population. Individuals with HCM can present
      with clinical manifestations that include left ventricular outflow obstruction,
      cardiac dysrhythmias, diastolic heart failure, cardiac angina, and sudden cardiac
      death. Current treatments include pharmacologic intervention to reduce heart rate
      and ventricular contractility as well as surgery or septal alcohol ablation to
      reduce myocardial septal size. Implantable cardiac defibrillators are considered
      a treatment option in individuals with HCM who are at an increased risk for
      sudden cardiac death. The identification of persons at risk for complications
      related to HCM is important for reducing mortality and morbidity in this
      population. In addition, diagnosis of HCM in an individual allows the healthcare
      provider caring for these patients to screen, educate, and institute timely
      preventative measures in other members of the family. The purpose of this review
      is to provide clinicians caring for cardiac patients with a guide for
      recognition, diagnosis, prevention, and treatment of HCM.

PMID- 17224702
TI  - Psychological factors and treatment adherence behavior in patients with chronic
      heart failure.
AB  - BACKGROUND: Chronic heart failure adversely affects 300,000 Australians. Symptom
      stabilization and prognosis are partially determined by patients following
      medical and lifestyle recommendations. METHODS: To test the hypothesis that
      depression, anxiety, and self-efficacy are independent predictors of such
      adherence, 115 predominantly male (70.6%) volunteers with a mean age of 63 years
      were recruited from a major teaching hospital in Australia. RESULTS: Depression
      (Beck Depression Inventory score >10, 33.3%) failed to predict adherence. Trait
      anxiety (State-Trait Anxiety Inventory score >40, 31%) explained minimal
      variability regarding smoking and alcohol adherence. Self-efficacy strongly
      predicted adherence behavior. CONCLUSIONS: Findings will assist cardiac nurses to
      prepare strategies to optimize adherence and quality of life while minimizing
      public health costs.

PMID- 17224703
TI  - Progress in prevention: cardiovascular risk reduction: the fountain of youth?

PMID- 17224704
TI  - Combined overdose of atomoxetine and methylphenidate in a cytochrome P450 2D6
      poor metabolizer.

PMID- 17224705
TI  - Why do clinical trials fail? The problem of measurement error in clinical trials:
      time to test new paradigms?

PMID- 17224706
TI  - Paliperidone extended-release tablets for prevention of symptom recurrence in
      patients with schizophrenia: a randomized, double-blind, placebo-controlled
      study.
AB  - We evaluated the efficacy of paliperidone extended-release (ER), an
      investigational psychotropic agent, in delaying symptom recurrence in adult
      patients with schizophrenia and its safety and tolerability. In this randomized,
      double-blind, placebo-controlled, multicenter study, patients' symptoms were
      stabilized during an 8-week run-in and a 6-week stabilization phases using open
      label, flexibly dosed paliperidone ER (3-15 mg once daily, starting dose = 9 mg).
      The primary efficacy variable was the time of first recurrence of schizophrenia
      symptoms, which included predefined changes in symptom scores, psychiatric
      hospitalization, self-injury, and suicidal or aggressive behavior during the
      double-blind phase (paliperidone ER or placebo treatment). Based on positive
      efficacy, the study was terminated at the preplanned interim analysis (43
      recurrence events). The interim analysis (primary analysis) included 113 patients
      (mean age = 41 years; 51% men, 85% white). In the intent-to-treat group, 14
      paliperidone ER-treated patients (25%) experienced a recurrence event versus 29
      (53%) for placebo. Time-to-recurrence was significantly different, favoring the
      paliperidone ER group (P = 0.005, log-rank test): 25% quantile of time-to
      recurrence was 83 days (paliperidone ER) versus 23 days (placebo). Final analyses
      (n = 205) were confirmatory. During initial open-label treatment with
      paliperidone ER, symptoms improved significantly. This improvement was maintained
      with continued treatment, as were functioning and quality-of-life measures.
      Treatment-emergent adverse events rates were similar: 35% for paliperidone ER and
      40% for placebo. Paliperidone ER treatment versus placebo significantly delayed
      time-to-recurrence in patients with schizophrenia, maintained symptom stability
      and measures of functioning, and was generally well tolerated in this patient
      population.

PMID- 17224707
TI  - Psychomotor and memory effects of haloperidol, olanzapine, and paroxetine in
      healthy subjects after short-term administration.
AB  - RATIONALE: Impaired psychomotor function has been shown to be associated with
      clinical and functional outcome in schizophrenia. However, few studies have
      investigated the short-term effects of antipsychotics on the cognitive and
      psychomotor functions of this patient group. Because many confounding factors
      tend to influence the test results in patient research, this study investigates
      the drugs' effects in healthy volunteers. OBJECTIVES: The short-term effects of
      haloperidol (2.5 mg), olanzapine (10 mg), and paroxetine (20 mg) on psychomotor
      function in 15 healthy volunteers are compared with placebo and each other.
      METHODS: In a crossover design, the subjects completed a battery of psychomotor
      tasks assessing psychomotor speed, sensorimotor accuracy, visuospatial
      monitoring, and speed of information processing. In addition, peak velocity of
      saccadic eye movements and subscales of the visual analog scales were analyzed as
      the objective and subjective measures for sedation, respectively. Finally, the
      verbal memory test was used to assess the drugs' effects on memory. RESULTS:
      Apart from affecting the pursuit task where visuospatial monitoring, sensorimotor
      speed, and sensorimotor accuracy are measured simultaneously, haloperidol has
      been proven to be not associated with sedative nor with impairing effects on
      psychomotor function or verbal memory. In contrast, olanzapine had significant
      sedative effects. Moreover, the subjects displayed a significant impairment on
      all measures of psychomotor function and verbal memory, which was not
      attributable to the drug's sedative effects. After administration of paroxetine,
      no effects were found, with the exception of a single improvement in eye movement
      velocity. CONCLUSIONS: Short-term administration of olanzapine, and not of
      haloperidol, impedes several aspects of psychomotor function and verbal memory in
      healthy volunteers.

PMID- 17224708
TI  - Weight gain during a double-blind multidosage clozapine study.
AB  - Possible variables associated with weight gain during clozapine treatment include
      dosing, treatment duration, baseline body mass index (BMI), sex, and plasma
      norclozapine concentrations. Weight gains during a double-blind, randomized
      clozapine study using 100-, 300-, and 600-mg/d doses were analyzed. It was
      hypothesized that weight gain was associated with baseline BMI, clozapine dosing,
      and demographic factors. The possible contribution of plasma clozapine and
      norclozapine concentrations was explored. Fifty treatment-refractory
      schizophrenia patients were randomized to 100-, 300-, or 600-mg/d doses of
      clozapine for a 16-week, double-blind treatment in a research ward. Nonresponsive
      patients went onto a second and/or a third 16-week, double-blind treatment at the
      other doses. Weights of patients were measured every week. During the first
      clozapine treatment, weight gain varied across 3 baseline BMI categories (normal
      weight patients [4.1 kg, P < 0.001], overweight patients [2.6 kg, P = 0.05], and
      obese patients [0.36 kg, not significant]) and according to dosing (600 mg/d [4.4
      kg], 300 mg/d [2.6 kg], and 100 mg/d [1.3 kg]). Sex had no effect after
      controlling for baseline BMI and dose, but the African-American race had a strong
      significant effect despite the small number of African Americans (n = 6). At the
      end of the first clozapine treatment, plasma norclozapine concentration was not
      significantly correlated with weight gain in the total sample (r = 0.16, P =
      0.32, n = 43), but seems to be strongly correlated in nonsmokers. Despite its
      limitations, this study indicates that baseline BMI, dosing, and, possibly, the
      African-American race may be major determinants of clozapine-induced weight gain.

PMID- 17224709
TI  - Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450
      2D6 function in healthy volunteers.
AB  - This study is the first to directly compare the relative effects of duloxetine,
      escitalopram, and sertraline on the functional activity of the drug-metabolizing
      cytochrome P450 2D6 enzyme as assessed by changes in the pharmacokinetics of the
      cytochrome P450 2D6 model substrate drug, metoprolol. Single-dose
      pharmacokinetics of metoprolol were measured before and after 17 days of
      treatment with escitalopram 20 mg/d, duloxetine 60 mg/d, or sertraline 100 mg/d
      in young healthy male and female participants. The outcome measures were changes
      in metoprolol peak plasma levels, area under the plasma concentration-time curve,
      and clearance. The results were tested using paired t tests and independent t
      tests. The addition of each drug produced statistically significant changes in
      metoprolol pharmacokinetics. The rank order for the change in metoprolol area
      under the plasma concentration-time curve was duloxetine (180%) > escitalopram
      (89%) > sertraline (48% and 67%). Compared with sertraline, duloxetine produced
      statistically significantly larger changes in metoprolol pharmacokinetic
      parameters. The changes produced by escitalopram and sertraline were not
      statistically different.

PMID- 17224710
TI  - Extrapyramidal adverse events associated with atypical antipsychotic treatment of
      bipolar disorder.
AB  - Second-generation antipsychotics (SGAs) have generally replaced classic
      neuroleptics in managing bipolar disorder because of their property of inducing
      extrapyramidal symptoms (EPS) less frequently than conventional agents. However,
      EPS and tardive dyskinesia both remain a concern especially in bipolar patients
      who may be at greater risk of developing these unwanted events. Hence, the aim of
      this study was to identify a definite rank order of EPS potential among such
      agents. All original research articles published in English on the use of SGAs
      for the treatment of bipolar patients were identified through a comprehensive
      Medline search. Only double-blind, randomized, placebo- and/or active comparator
      controlled studies evaluating the effectiveness of atypical antipsychotics in
      bipolar patients were included in this article. Available literature data seem to
      suggest that EPS may occur in a significantly greater proportion of aripiprazole
      treated patients than placebo-treated patients. The relevant bias characterizing
      most of quetiapine trials makes the finding that the incidence of EPS does not
      differ statistically between medicated and placebo groups doubtful. Among SGAs,
      risperidone seems to be associated with the highest risk of inducing EPS at doses
      lower than 6 mg/d. Conversely, data on olanzapine appear to be quite reassuring.
      Although it has been reported that there are no statistically significant
      differences between ziprasidone- and placebo-treated patients in the incidence
      rates of EPS, this information requires further confirmation. Thus, as it regards
      the risk of inducing EPS, among SGAs, olanzapine should be considered a first
      choice medication for bipolar patients. However, clinicians should take into
      consideration the relatively high risk of metabolic complications associated with
      olanzapine use as well as with most of the other SGAs.

PMID- 17224711
TI  - Second-generation antipsychotic exposure and metabolic-related disorders in
      patients with schizophrenia: an observational pharmacoepidemiology study from
      1988 to 2002.
AB  - Patients with schizophrenia are at increased risk for cardiovascular disease as a
      consequence of lifestyle habits, impaired access to health care, and,
      increasingly, due to metabolic side effects ostensibly attributed to second
      generation antipsychotics (SGAs). There is little evidence, however, on the
      extent and temporal patterns of SGA-associated metabolic side effects. We
      longitudinally examined the differential prevalence rates of obesity, diabetes
      mellitus, and diabetic ketoacidosis among inpatients with schizophrenia compared
      with control inpatients without schizophrenia. The data were derived from the
      National Inpatient Sample, the largest all-payer inpatient care database in the
      United States consisting of 5 to 8 million inpatient hospital stays per year
      sampled to approximate a 20% sample of community hospitals from 1988 to 2002.
      Overlaid on these observations was the market penetration data for SGAs. In 1988,
      the net difference from controls in obesity prevalence among inpatients with
      schizophrenia was +4.7%; by 2002, this difference had widened to +14.7%.
      Similarly, a significant increase in net prevalence of diabetes mellitus and
      diabetic ketoacidosis was observed from 1988 to 2002 among schizophrenic
      inpatients. In conclusion, after the introduction of SGAs, patients with
      schizophrenia in the United States have experienced a striking net increase in
      the prevalence of obesity and diabetes mellitus. This is likely to significantly
      add to an already elevated risk for cardiovascular disease in this population.
      Further investigations are urgently required so that health policy can be
      appropriately amended for preventive measures.

PMID- 17224713
TI  - Prolactin release in children treated with risperidone: impact and role of CYP2D6
      metabolism.
AB  - OBJECTIVE: Little is known about the role of CYP2D6 polymorphism in risperidone
      induced prolactin release in children. METHOD: Twenty-five children (aged 5-15
      years) with pervasive developmental disorders were genotyped for CYP2D6
      polymorphisms. Serum prolactin, risperidone, and 9-hydroxyrisperidone were
      assessed at baseline and after 8 weeks of risperidone treatment (mean dosage,
      0.06 +/- 0.03 mg/kg/d). After 24 weeks of treatment, prolactin was measured in a
      subsample of 15 children. Adverse effects were evaluated using a clinician-rated
      survey. RESULTS: Mean +/- SD prolactin levels increased from 7.8 +/- 8.0 ng/mL at
      baseline to 33.2 +/- 12.8 ng/mL at week 8 (P < 0.001), with a slight decrease to
      28.8 +/- 13.6 ng/mL at week 24. At week 8, serum prolactin level was positively
      correlated with dose per kilogram (r = 0.648, P < 0.001), number of functional
      CYP2D6 genes (J = 2.117, P = 0.034), and serum 9-hydroxyrisperidone concentration
      (r = 0.664, P = 0.001) and was negatively correlated with the risperidone/9
      hydroxyrisperidone ratio (r = -0.571, P = 0.004) but not with risperidone
      concentration (r = -0.243, P = 0.264) nor age (r = 0.072, P = 0.733). Prolactin
      elevation was not associated with adverse effects. CONCLUSIONS: Low-to
      intermediate doses of risperidone induced a 4-fold prolactin increase in children
      without a clear development of tolerance up to 6 months. CYP2D6 ultrarapid
      metabolism may be a risk factor for more pronounced prolactin elevation.

PMID- 17224714
TI  - Antidepressant therapy can improve adherence to antiretroviral regimens among HIV
      infected and depressed patients.
AB  - Several strategies have been introduced to manage nonadherence to highly active
      antiretroviral therapy (HAART). Treatment with antidepressants may improve self
      reported adherence. In this brief report, a small sample of HIV-depressed
      patients (n = 9) were treated for a 6-month period with antidepressants improving
      self-reported adherence based on the HAART scale (poor, good, satisfactory, and
      optimal). Before the antidepressant treatment, adherence was reported as "good"
      by 3 patients and "satisfactory" by 6 patients. After antidepressant therapy,
      adherence to antiretroviral regimes was statistically higher in HIV-depressed on
      treatment than in HIV-depressed patients not treated with antidepressants (P <
      0.0001). We used chi2 test with a significance level at P < 0.05. Treating
      depression in HIV-infected patients may serve to improve adherence to HAART.

PMID- 17224715
TI  - Tadalafil for treatment of erectile dysfunction in men on antidepressants.
AB  - OBJECTIVE: The objective of this post hoc analysis was to evaluate tadalafil, a
      treatment indicated for erectile dysfunction (ED), in men on antidepressants.
      METHOD: A retrospective, pooled analysis of 19 double-blind, placebo-controlled
      trials (N = 3864) identified 205 men with ED, mean age of 55 years (range, 27-79
      years) receiving antidepressants and tadalafil 10 mg (n = 38), tadalafil 20 mg (n
      = 113), or placebo (n = 54). Efficacy was measured by the International Index of
      Erectile Function erectile function domain score, the Sexual Encounter Profile
      diary, and a Global Assessment Question. Tolerability was assessed via collection
      and analysis of treatment-emergent adverse events. RESULTS: Patients on
      antidepressants who were treated with tadalafil showed significantly greater
      baseline-to-end point improvement on the International Index of Erectile Function
      score compared with placebo (end point: tadalafil 10 mg, 21.7; tadalafil 20 mg,
      21.8; placebo, 14.5; both P < 0.01). The mean per-patient percent successful
      intercourse postbaseline was also greater with tadalafil 10 mg (54%) and
      tadalafil 20 mg (59%) than placebo (29%, both P < 0.05). Patients taking
      tadalafil 10 (72%) and 20 (76%) mg both reported significant improvement in
      erections on the Global Assessment Question compared with placebo (33%, both P <
      0.01). The incidence of treatment-emergent adverse events was low in all
      treatment groups with the most common being headache, dyspepsia, and back pain.
      CONCLUSION: Tadalafil was well tolerated and improved erectile function in
      patients taking antidepressant medications.

PMID- 17224716
TI  - Does fluoxetine have any effect on the cognition of patients with mild cognitive
      impairment? A double-blind, placebo-controlled, clinical trial.
AB  - OBJECTIVES: Mild cognitive impairment (MCI) may be a prodromal state for
      Alzheimer disease. Recent research suggest a role for other neuronal systems such
      as monoaminergic hypofunction beside cholinergic dysfunction in age-related
      cognitive decline. In several studies, selective serotonin reuptake inhibitors
      demonstrated promotion of neurogenesis in the hippocampus. In this study, the
      effects of fluoxetine, a selective serotonin reuptake inhibitor, on memory and
      cognition of patients with mild cognitive impairment has been studied. METHOD:
      Fifty-eight nondepressed patients with MCI were randomly assigned to take
      fluoxetine or placebo. The patients were administered the Structured Clinical
      Interview for DSM-IV (Diagnosis and Statistical Manual for Mental Disorders,
      Fourth Edition) Disorders, the Mini-Mental Status Examination (MMSE), subtests
      from the Persian standardized Wechsler Memory Scale III (WMS-III)
      preintervention. Forty-four patients completed the 8-week trial. Treatment
      response was defined as improvement in the scores of MMSE, subtests of WMS-III,
      and Clinical Global Impression. RESULT: The patients in the fluoxetine group
      showed improvement in MMSE and immediate and delayed logical memory scores of WMS
      III. The placebo group had no significant changes in the cognitive measurements.
      CONCLUSION: Fluoxetine enhanced memory and cognition in the patients. This was
      consistent with previous studies that emphasized the role of fluoxetine in
      improving memory and promoting neurogenesis in the hippocampus. However, this is
      a preliminary study with small sample size, and larger double-blind placebo
      controlled studies are needed to confirm these findings.

PMID- 17224717
TI  - Displacement of serotonin and dopamine transporters by venlafaxine extended
      release capsule at steady state: a [123I]2beta-carbomethoxy-3beta-(4-iodophenyl)
      tropane single photon emission computed tomography imaging study.
AB  - Both positron emission tomography and single photon emission computed tomography
      (SPECT) studies suggest that saturation of serotonin transporters (SERT) is
      present during treatment with therapeutic doses of selective serotonin reuptake
      inhibitors (SSRIs). Selective serotonin reuptake inhibitors also appear to
      increase the availability of dopamine transporters (DAT). The current study
      measured SERT occupancy and modulation of DAT by the serotonin/norepinephrine
      reuptake inhibitor (SNRI) venlafaxine using [123I]2beta-carbomethoxy-3beta-(4
      iodophenyl)-tropane SPECT. Eight healthy subjects were administered open-label
      venlafaxine extended release capsules (75 mg/d for 4 days followed by 150 mg/d
      for 5 days). Venlafaxine significantly inhibited [123I]beta-CIT binding to SERT
      in the brainstem (55.4%) and the diencephalon (54.1%). In contrast, venlafaxine
      increased [123I]beta-CIT binding to DAT in the striatum (10.1%) after 5 days of
      administration of 150 mg/d. The displacement of [123I]beta-CIT from brain SERT
      and the increase in striatal [123I]beta-CIT binding to DAT appear similar to
      previous work with the SSRI citalopram (40 mg/d). A literature review of SERT
      occupancy by marketed SSRIs and the SNRI venlafaxine using SPECT ([123I]beta-CIT)
      or positron emission tomography ([11C](N, N-Dimethyl-2-(2-amino-4
      cyanophenylthio)-benzylamine) imaging suggests that therapeutic doses of SNRI are
      associated with virtual saturation of the serotonin transporter.

PMID- 17224718
TI  - A randomized, double-blind, crossover trial of modafinil on mood.
AB  - Modafinil, a medication for the excessive sleepiness associated with narcolepsy,
      has been hypothesized to improve not just alertness but mood as well. The purpose
      of this study was to determine how treatment with modafinil affects mood in
      healthy volunteers. Normal healthy volunteers (n = 12, 10 men and 2 women; 30-44
      years) underwent a 3-day, counterbalanced, randomized, crossover, inpatient trial
      of modafinil (400 mg daily) versus placebo with 4-day washout period between 2
      treatments. Mood was assessed daily using both the Positive and Negative Affect
      Schedule and a general mood scale, which consisted of 10 bipolar adjective
      ratings based on a severity scale ranging from 1 to 10. Modafinil increased
      general mood and Negative Affect scales relative to placebo and had a significant
      effect on Positive Affect scales. These results suggest that modafinil may have
      general mood-elevating effects accompanied by increased negative affect
      (anxiety). The findings may have implications for clinical practice, in
      particular for the adjunctive use of modafinil in treatment-resistant depression.

PMID- 17224719
TI  - Abnormal hippocampal neurochemistry in smokers: evidence from proton magnetic
      resonance spectroscopy at 3 T.
AB  - OBJECTIVE: In animals, nicotine, the primary psychoactive constituent of tobacco
      smoke, reduces neurogenesis and increases cell loss in both hippocampus and
      cortex. Accordingly, tobacco smoking has been linked to reduced performance on
      cognitive paradigms requiring attention and working memory in humans. However,
      few prior studies have tested for evidence of structural brain alterations in
      human tobacco smokers. In this study, proton magnetic resonance spectroscopy was
      used to assess the effects of chronic smoking on neuronal integrity of the
      hippocampus and anterior cingulate cortex (ACC). METHODS: Absolute concentrations
      of N-acetylaspartate, total choline (tCho), and total creatine were measured in
      the left hippocampus and ACC in 13 chronic tobacco smokers and 13 nonsmokers
      matched for age, sex, and education. RESULTS: The N-acetylaspartate concentration
      was significantly reduced in smokers relative to nonsmokers in the left
      hippocampus but not in the ACC. There were no group differences in the tCho and
      total creatine concentrations in either voxel. However, ACC tCho concentration
      was positively correlated with magnitude of lifetime exposure to tobacco smoke
      (pack-years). CONCLUSION: The results are consistent with prior observations of
      hippocampal neuronal damage in rodents receiving nicotine and working memory
      deficits in human tobacco smokers. The positive relationship between tCho and
      lifetime tobacco exposure suggests that a component of tobacco smoke, presumably
      nicotine, may increase cortical membrane turnover or modify cell density.
      Together, these results add to growing evidence that nicotine exerts neurotoxic
      effects in human brain, although an a priori nature of the findings cannot be
      ruled out.

PMID- 17224720
TI  - The efficacy and tolerability of tiagabine in adult patients with post-traumatic
      stress disorder.
AB  - The aim of this study was to evaluate the efficacy and tolerability of tiagabine
      in adult patients with post-traumatic stress disorder (PTSD). This 12-week,
      multicenter, double-blind study randomized patients to receive either tiagabine
      or placebo. Tiagabine (administered in divided doses) was initiated at 4 mg/d (2
      mg BID) and individually titrated of up to 4 mg/d weekly to a maximum dose of 16
      mg/d. Assessments included the Clinician-Administered PTSD Scale, Clinical Global
      Impressions of Change, Treatment Outcome PTSD Scale, Davidson Trauma Scale,
      Connor-Davidson Resilience Scale, Sheehan Disability Scale, Massachusetts General
      Hospital Sexual Functioning Questionnaire, and Montgomery-Asberg Depression
      Rating Scale. A total of 232 patients (tiagabine, n = 116; placebo, n = 116) were
      randomized. There were no significant differences in change from baseline in the
      Clinician-Administered PTSD Scale total score at final visit for tiagabine
      compared with placebo (P = 0.85). Similarly, no significant differences were
      observed with tiagabine on the other efficacy outcome measures (described above)
      compared with placebo. Tiagabine was generally well tolerated and not associated
      with weight gain, changes in sexual function, or worsening of depressive
      symptoms. Tiagabine was not significantly different from placebo in the treatment
      of symptoms of PTSD. Additional studies are needed to assess the role of drugs
      that target the gamma-aminobutyric acid system in the treatment of PTSD.

PMID- 17224721
TI  - Clozapine-associated restless legs syndrome.

PMID- 17224722
TI  - A case-control study of patients with resistant schizophrenia after clozapine
      discontinuation.

PMID- 17224723
TI  - Transient hyperglycemia and decreased glucose tolerance during antipsychotic
      monotherapy with amisulpride.

PMID- 17224724
TI  - Attitude of patients with mood disorder toward clinical trials in Japan.

PMID- 17224725
TI  - Venlafaxine discontinuation syndrome and suicidal ideation: a case series.

PMID- 17224726
TI  - Sex differences in antidepressant response in a Canadian primary-care sample.

PMID- 17224727
TI  - Fluvoxamine in the treatment of late-life depression: how much we know coming
      from randomized controlled trials: comment on article by Dr Rossini and
      colleagues.

PMID- 17224728
TI  - Suicidality scores during double-blind fluoxetine and desipramine treatment in
      Mexican Americans.

PMID- 17224730
TI  - Duloxetine and hyponatremia: a report of 5 cases.

PMID- 17224731
TI  - A 2-year, open-label pilot study of adjunctive chromium in patients with
      treatment-resistant rapid-cycling bipolar disorder.

PMID- 17224732
TI  - Quetiapine in a case with Parkinson disease and pathological gambling.

PMID- 17224733
TI  - Duloxetine-induced excessive disturbing and disabling yawning.

PMID- 17224734
TI  - Inhibition of selective noradrenergic reuptake as treatment of pathological
      laughter.

PMID- 17224735
TI  - First case of sialolithiasis associated with atomoxetine.

PMID- 17224736
TI  - The Asp40 mu-opioid receptor allele does not predict naltrexone treatment
      efficacy in heavy drinkers.

PMID- 17224737
TI  - Duloxetine-induced ultrarapid cycling in an adolescent with bipolar depression.

PMID- 17224739
TI  - Rating the raters--who is the research subject?

PMID- 17224740
TI  - Gabapentin-related changes in renal function: two case reports.

PMID- 17224742
TI  - Usefulness of optical coherence tomography parameters of the optic disc and the
      retinal nerve fiber layer to differentiate glaucomatous, ocular hypertensive, and
      normal eyes.
AB  - PURPOSE: To assess Stratus optical coherence tomography (OCT) original parameters
      for identifying glaucomatous damage and to evaluate differences among
      glaucomatous, ocular hypertensive, and normal eyes. DESIGN: Cross-sectional
      prospective study. SUBJECTS AND METHODS: The study was conducted at 2 centers.
      The study population consisted of 55 normal individuals, 95 patients with ocular
      hypertension (OHT), and 79 patients with glaucoma. Retinal nerve fiber layer
      (RNFL) and optic nerve head OCT protocols were used to evaluate all study
      participants. Measurements taken were RNFL thickness, several ratios, RNFL
      asymmetry between both eyes, rim volume, rim width, disc area, cup area, rim
      area, cup/disc (C/D) area ratio, and horizontal and vertical C/D ratios. The main
      outcome measures were the differences in OCT parameters among groups and the
      areas under the receiver operating characteristic curves (AROC). RESULTS: Mean
      RNFL thickness around the disc, and superior and inferior RNFL thickness, were
      significantly thinner in glaucomatous eyes than in OHT or normal eyes (P<0.001).
      Rim parameters were significantly smaller in glaucomatous eyes than in normal
      (P<0.001) and OHT eyes (P=0.01). C/D ratios were significantly greater in
      glaucomatous eyes than in OHT (P<0.001) and normal (P<0.001) eyes. Significant
      differences were found between normal and OHT eyes in 7 disc parameters. No
      difference was found among groups in parameters describing RNFL asymmetry between
      both eyes. The AROC curves of the other RNFL and disk parameters ranged from
      0.741 to 0.85. CONCLUSIONS: Almost all RNFL and disc parameters showed
      significant differences and discriminated between glaucomatous and normal eyes.
      There were significant differences in some optic nerve parameters, but no RNFL
      parameters, between normal and OHT eyes.

PMID- 17224743
TI  - Frequency doubling technology perimetry in open-angle glaucoma eyes with
      hemifield visual field damage: comparison of high-tension and normal-tension
      groups.
AB  - PURPOSE: To evaluate the performance of frequency doubling technology (FDT)
      perimetry in open-angle glaucoma eyes with hemifield visual field damage and to
      compare it between open-angle glaucoma with high pressure [high-tension glaucoma
      (HTG)] and those with normal pressure [normal-tension glaucoma (NTG)] groups.
      METHODS: FDT perimetry with the N-30 full threshold protocol and standard
      automated perimetry (SAP) using the Humphrey Field Analyzer with the 30-2 full
      threshold protocol were performed in 20 eyes of 20 HTG patients and 36 eyes of 36
      NTG patients with visual field damage confirmed with SAP in only one hemifield.
      RESULTS: There was no significant difference in demographics, the Heidelberg
      Retina Tomography indices, and the Humphrey Field Analyzer indices between HTG
      and NTG groups. Regarding the FDT perimetry results, mean deviation in the global
      field (P=0.009) and mean sensitivity in the SAP-spared (P=0.001) and SAP-impaired
      (P=0.011) hemifields were lower; the numbers of FDT abnormal test points
      (probability of abnormality <5%) in the SAP-spared hemifield were significantly
      greater (P=0.005) in HTG than in NTG groups. Eyes in which FDT results of the SAP
      spared hemifield were judged as abnormal was more frequent in HTG groups
      (P=0.007). CONCLUSIONS: The performance of FDT perimetry to detect early or
      preperimetric glaucomatous functional changes should be different between HTG and
      NTG eyes.

PMID- 17224744
TI  - Comparison of trabeculectomy with Ex-PRESS miniature glaucoma device implanted
      under scleral flap.
AB  - PURPOSE: To evaluate the Ex-PRESS miniature implant (Model R 50) placed under
      partial-thickness scleral flap compared with standard trabeculectomy. METHODS: In
      this retrospective comparative series of 100 eyes, we compared 50 eyes in 49
      patients treated with the Ex-PRESS miniature glaucoma implant under a scleral
      flap with 50 matched control eyes in 47 patients treated with trabeculectomy.
      Success was defined as intraocular pressure (IOP) > or =5 mm Hg and < or =21 mm
      Hg, with or without glaucoma medications, without further glaucoma surgery or
      removal of implant. Early postoperative hypotony was defined as IOP <5 mm Hg
      during the first postoperative week. RESULTS: The average follow-up was 10.8
      months (range 3.5 to 18) for the Ex-PRESS group and 11.2 months (range 3 to 15)
      for the trabeculectomy group. Although the mean IOP was significantly higher in
      the early postoperative period in the Ex-PRESS group compared with the
      trabeculectomy group, the reduction of IOP was similar in both groups after 3
      months. The number of postoperative glaucoma medications in both groups was not
      significantly different. Kaplan-Meier survival curve analysis showed no
      significant difference in success between the 2 groups (P=0.594). Early
      postoperative hypotony and choroidal effusion were significantly more frequent
      after trabeculectomy compared with Ex-PRESS implant under scleral flap (P<0.001).
      CONCLUSIONS: The Ex-PRESS implant under a scleral flap had similar IOP-lowering
      efficacy with a lower rate of early hypotony compared with trabeculectomy.

PMID- 17224745
TI  - Trained artificial neural network for glaucoma diagnosis using visual field data:
      a comparison with conventional algorithms.
AB  - PURPOSE: To evaluate and confirm the performance of an artificial neural network
      (ANN) trained to recognize glaucomatous visual field defects, and compare its
      diagnostic accuracy with that of other algorithms proposed for the detection of
      visual field loss. METHODS: SITA Standard 30-2 visual fields, from 100 glaucoma
      patients and 116 healthy participants, formed the data set. Our ANN was a
      previously described fully trained network using scored pattern deviation
      probability maps as input data. Its diagnostic accuracy was compared to that of
      the Glaucoma Hemifield Test, the Pattern Standard Deviation index at the P<5% and
      <1%, and also to a technique based on the recognizing clusters of significantly
      depressed test points. RESULTS: The included tests had early to moderate visual
      field loss (median MD=-6.16 dB). ANN achieved a sensitivity of 93% at a
      specificity level of 94% with an area under the receiver operating characteristic
      curve of 0.984. Glaucoma Hemifield Test attained a sensitivity of 92% at 91%
      specificity. Pattern Standard Deviation, with a cut off level at P<5% had a
      sensitivity of 89% with a specificity of 93%, whereas at P<1% the sensitivity and
      specificity was 72% and 97%, respectively. The cluster algorithm yielded a
      sensitivity of 95% and a specificity of 82%. CONCLUSIONS: The high diagnostic
      performance of our ANN based on refined input visual field data was confirmed in
      this independent sample. Its diagnostic accuracy was slightly to considerably
      better than that of the compared algorithms. The results indicate the large
      potential for ANN as an important clinical glaucoma diagnostic tool.

PMID- 17224746
TI  - Diurnal variation of central corneal thickness and Goldmann applanation tonometry
      estimates of intraocular pressure.
AB  - PURPOSE: To determine whether there is a temporal relationship between the
      diurnal variation of central corneal thickness (CCT) and intraocular pressure
      (IOP) by Goldmann applanation tonometry in young normal human participants in
      vivo. METHODS: Twenty-five eyes of 25 young healthy normal participants were
      examined in a prospective observational cross-sectional study. IOP, CCT and
      corneal curvature were measured using standard clinical techniques over a 24-hour
      period, and the temporal interrelationships between these parameters were
      examined. RESULTS: The overnight change in IOP measured by Goldmann tonometry was
      3.1+/-2.4 mm Hg (P<0.001), CCT was 20.1+/-10.9 mum (P=0.016), with no statistical
      change in central corneal curvature (0.05 mm, P=0.477, paired t test with
      Bonferroni correction). Both IOP and CCT were highest on awakening at 7:00 then
      dropped rapidly to baseline levels by 9:00 (linear mixed models), and these two
      parameters were highly correlated (r=0.978, P<0.001). After 9:00, there was no
      correlation between these parameters (r=-0.453, P=0.260). CONCLUSIONS: The
      results of this study have highlighted a potential link between the diurnal
      variation of CCT and the accuracy of Goldmann tonometry estimates of IOP during
      the first 2 hours after awakening. Clinicians should be wary of using Goldmann
      tonometry to estimate IOP until the overnight increase in CCT has resolved.

PMID- 17224747
TI  - Comparison of silicone and polypropylene Ahmed Glaucoma Valve implants.
AB  - PURPOSE: To compare the efficacy and safety of silicone and polypropylene Ahmed
      Glaucoma Valves (AGVs) in patients with refractory glaucoma. METHODS: A
      retrospective chart review of 180 eyes of 166 patients who underwent AGV
      implantation with a minimum follow-up period of 3 months was performed. All
      patients who underwent implantation of either the AGV model S-2 (polypropylene)
      or model FP-7 (silicone) were included, unless previous laser
      cyclophotocoagulation had been performed. The primary outcome measures were the
      change in intraocular pressure (IOP) and visual acuity after surgery and the rate
      of postoperative complications. RESULTS: No significant differences were seen in
      the baseline characteristics of patients in each group. Baseline IOP was
      statistically equivalent in the 2 groups (silicone =33.8+/-11.9 mm Hg,
      polypropylene=33.0+/-10.3 mm Hg, P=0.6). A significant reduction in IOP from
      baseline was achieved after both silicone and polypropylene AGV implantation
      (silicone =-17.7+/-11.8 mm Hg, polypropylene =-17.7+/-11.3 mm Hg, both
      P<0.00005). However, there was no statistically significant difference in IOP
      decrease between the 2 groups at any follow-up visit (all P>0.09). The mean
      number of postoperative antiglaucoma medications was also similar in the silicone
      and the polypropylene AGV groups at each time point (all P>0.2). The rate of
      complications and the change in visual acuity did not differ between the 2 groups
      (P>0.6 and P>0.3, respectively). CONCLUSIONS: Silicone and polypropylene AGVs
      have similar results with respect to both safety and efficacy in the treatment of
      patients with refractory glaucoma.

PMID- 17224748
TI  - Prevalence of normal tension glaucoma in obstructive sleep apnea syndrome
      patients.
AB  - PURPOSE: To explore the prevalence of normal tension glaucoma (NTG) among
      patients with obstructive sleep apnea syndrome (OSAS) and to examine OSAS as a
      risk factor of NTG. PATIENTS AND METHODS: Fifty-one consecutive white patients
      with OSAS were compared with 40 healthy subjects. All the study subjects
      underwent blood gas analysis, polysomnography, oxyhemoglobin saturation, and an
      ophthalmologic examination including visual field, visually evoked potential
      (VEP), and pattern electroretinography (PERG) and disc analysis with the
      Heidelberg Retina Tomograph II. RESULTS: Three of 51 OSAS patients (5.9%) had
      NTG. No patient in the control group had OSAS or NTG. The severity of OSAS
      correlated with intraocular pressure, the mean deviation of the visual field, the
      cup/disk ratio and the mean of the retinal nerve fiber layer thickness (P<0.01 to
      0.001). Apnea hypopnea index and intraocular pressure were significantly greater
      in OSAS patients with abnormal VEP and PERG, compared to those with normal PERG
      and VEP. CONCLUSIONS: The present study suggests that the prevalence of NTG in
      our OSAS patients is higher than expected in a white population of the same age
      and that OSAS may be an important risk factor for NTG. Our data underline the
      importance of taking an accurate sleep history from patients with NTG and
      referring patients with sleep disturbance for polysomnography.

PMID- 17224749
TI  - No increased risk of developing Alzheimer disease in patients with glaucoma.
AB  - PURPOSE: To investigate whether primary open-angle glaucoma (POAG) is associated
      with increased risk of developing Alzheimer disease (AD). METHODS: In a
      nationwide case register linkage study of patients with hospital admission or
      outpatient contact during the period from 1977 to 2001 in Denmark, the rate of
      subsequent AD for patients with a diagnosis of POAG was compared with the rate
      for patients with primary angle-closure glaucoma (PACG), cataract, and
      osteoarthritis (OA) and with the rate for the general population. RESULTS: A
      total of 11,721 patients with a diagnosis of POAG (including normal tension
      glaucoma), 5975 patients with PACG, 162,640 patients with cataract, and 230,208
      patients with OA were identified in the registers. Patients with POAG did not
      have increased rate of subsequent AD compared to patients with PACG, cataract, or
      OA or compared with the general population. CONCLUSIONS: POAG was not associated
      with increased risk of developing AD. It cannot be excluded that this negative
      finding is due to diagnostic misclassification as register data were used.

PMID- 17224750
TI  - Primary trabeculectomy surgery performed by residents at a county hospital.
AB  - PURPOSE: To evaluate the safety and efficacy of trabeculectomies performed by
      ophthalmology residents at a metropolitan county hospital, under the supervision
      of attending physicians. METHODS: A retrospective analysis of resident-performed
      trabeculectomies at the San Francisco General Hospital from the period of 1994 to
      2004 was performed. The preoperative and postoperative ocular data of 50 eyes in
      35 patients were evaluated. Of the 50 cases, 47 procedures were performed as
      primary trabeculectomies and 3 were revisions of trabeculectomies. RESULTS: The
      average follow-up period was 28.9+/-17.6 months with an intraocular pressure
      (IOP) decrease from 23.2+/-9.4 mm Hg preoperatively to 11.3+/-4.4 mm Hg at last
      follow-up, for a mean reduction of 11.9+/-10.5 mm Hg (51.6%) (P<0.0001). Follow
      up periods ranged from 3 months to over 6 years. The number of medications
      required decreased from 3.2+/-1.1 to 0.6+/-0.1 (P<0.0001). Success, defined by a
      postoperative IOP < or =21 mm Hg or a decreased postoperative IOP of at least 25%
      from preoperative pressure if the preoperative IOP was already < or =21 mm Hg,
      was observed in 42 eyes (84%) at last follow-up. Best-corrected visual acuity was
      stable or improved in 22 eyes (44%) and was noted to decrease 2 or more Snellen
      lines in 28 eyes (56%). Notable complications included 3 cases (6%) of persistent
      hypotony (IOP<5), 1 case (2%) of late endophthalmitis, and 1 case (2%) of
      phthisis. Seven eyes (14%) required subsequent penetrating glaucoma procedures
      due to bleb failure. CONCLUSIONS: Results of this study suggest that the outcomes
      of trabeculectomies performed by residents at a county hospital can have a high
      success rate, comparable with previous studies in the literature. Rates of
      complications are overall similar to those found in the published literature.

PMID- 17224751
TI  - Noninvasive determination of intraocular pressure (IOP) in nonsedated mice of 5
      different inbred strains.
AB  - BACKGROUND: Noninvasive intraocular pressure (IOP) measurement in mice is
      critically important for understanding the pathophysiology of glaucoma. Rebound
      tonometry is one of the methods that can be used for obtaining such measurements.
      We evaluated the ability of the rebound tonometer (RT) to determine IOP
      differences among various mouse strains and whether differences in corneal
      thickness may affect IOP measurements in these animals. MATERIALS AND METHODS:
      Five different commonly used mouse strains (BALB/C, CBA/CAHN, AKR/J, CBA/J, and
      129P3/J) were used. IOP was measured in eyes from 12 nonsedated animals (6 male
      and 6 female) from each strain at 2 to 3 months of age using the RT. IOPs were
      measured in all animals, on 2 different days between 10 AM and 12 PM.
      Subsequently, a number of eyes from each strain were cannulated to provide a
      calibration curve specific for that strain. Tonometer readings for all strains
      were converted to apparent IOP values using the calibration data obtained from
      the calibration curve of the respective strain. For comparison purposes, IOP
      values were also obtained using the C57BL/6 calibration data previously reported.
      IOP for the 5 strains, male and female animals, and the different occasion of
      measurement were compared using repeat measures analysis of variance. The central
      corneal thickness (CCT) of another group of 8 male animals from each of the 5
      strains was also measured using an optical low coherence reflectometry (OLCR)
      pachymeter modified for use with mice. CCT values were correlated to mean IOPs of
      male animals and to the slopes and intercept of individual strain calibration
      curves. RESULTS: Noninvasive IOP measurements confirm that the BALB/C strain has
      lower and the CBA/CAHN has higher relative IOPs than other mouse strains while
      the AKR/J, the CBA/J, and the 129P3/J strains have intermediate IOPs. There is a
      very good correlation of apparent IOP values obtained by RT with previously
      reported true IOPs obtained by cannulation. There was a small but statistically
      significant difference in IOP between male and female animals in 2 strains
      (129P3/J and AKR/J) with female mice having higher relative IOPs. No correlation
      between CCT and IOP was detected. CCT did not correlate with any of the constants
      describing the calibration curves in the various strains. CONCLUSIONS:
      Noninvasive IOP measurement in mice using the RT can be used to help elucidate
      IOP phenotype, after prior calibration of the tonometer. CCT has no effect on
      mouse IOP measurements using the RT.

PMID- 17224752
TI  - Intraluminal pressure response in Baerveldt tube shunts: a comparison of
      modification techniques.
AB  - PURPOSE: To design an apparatus for in vitro quantification of effects of
      modifications to nonvalved tube shunts, and to compare the effects of these
      modifications done to prevent early postoperative hypotony. MATERIALS AND
      METHODS: A testing apparatus was designed and constructed to measure intraluminal
      pressure (ILP) during constant infusion of balanced salt solution at 2 microL/min
      through Baerveldt tube shunts mounted on cadaver eyes. Three different
      modifications were performed and 3 shunts were used for each modification. The
      modifications were partial tube occlusion with a 3-0 Supramid suture, tube
      perforation with a 27-gauge needle on an occluded tube, and a 1.2 mm longitudinal
      venting slit on an occluded tube. RESULTS: The final steady state ILP for the 3-0
      Supramid partially occluded tube ranged between 1.6 and 2.8 mm Hg over 3 trials
      with an average final steady state ILP of 2.0 mm Hg. The 27-gauge needle
      perforation produced ILPs of 4.6 to 8.2 mm Hg over 3 trials with an average final
      steady state pressure of 5.9 mm Hg. The 1.2 mm longitudinal venting slit produced
      an ILP range of 12.6 to 17.3 mm Hg over 3 trials with an average final steady
      state ILP of 14.8 mm Hg. The differences in final steady state ILP between the 3
      modification techniques were statistically significant (P=0.00036). CONCLUSIONS:
      The 3-0 Supramid occlusion and the 27-gauge perforation techniques produced
      hypotony, whereas the 1.2 mm longitudinal venting slit produced acceptable
      pressures in vitro.

PMID- 17224753
TI  - Trabeculectomy with mitomycin C in secondary glaucoma associated with Behcet
      disease.
AB  - PURPOSE: To determine the outcome of initial trabeculectomy with mitomycin C
      (MMC) in the management of secondary glaucoma associated with Behcet disease (BD)
      in a 1-year follow-up period. METHODS: Twenty-three eyes of 13 cases with
      secondary glaucoma associated with BD, were evaluated prospectively. They
      underwent primary trabeculectomy with MMC. The operative success was defined as
      an intraocular pressure (IOP) < or =20 mm Hg (+/- medical therapy) in the absence
      of phthisis and without the necessity of further surgery for glaucoma and success
      rates at the postoperative first day, first month, sixth month, and first year
      were determined. RESULTS: Success was achieved in all of the eyes (100%) at the
      postoperative first day and month, in 21 eyes (91.3%) at the postoperative sixth
      month and in 19 eyes (82.6%) at the postoperative first year. The mean
      preoperative IOP was 30.9+/-5.3 mm Hg under the mean 3.3+/-0.7 antiglaucoma
      medications but it reduced to 16.8+/-3.1 mm Hg under the mean 1.7+/-0.8
      medications at the postoperative sixth month and 18.5+/-3.2 mm Hg under the mean
      2.6+/-1.1 medications at the postoperative first year. CONCLUSIONS:
      Trabeculectomy with MMC provides reduction of IOP and the number of antiglaucoma
      medications in cases with secondary glaucoma associated with BD in a 1-year
      follow-up period.

PMID- 17224754
TI  - The results of screening frequency doubling technology perimetry in different
      locations of the community.
AB  - PURPOSE: To determine the effect of screening location on the frequency of
      abnormal test results with Frequency Doubling Technology (FDT) perimetry. DESIGN:
      Retrospective cross-sectional study. METHODS: The Vision Screening Outreach
      Project conducted FDT testing in community sites surrounding Portland, Oregon.
      The sites were separated into a specific location type: health care clinics, work
      sites, senior centers, festivals/fairs, food banks/shelters, and other locations.
      These locations were compared for differences in the proportion of screening
      failures. MAIN OUTCOME MEASURES: Screening failure (defined as a repeatable,
      abnormal FDT result in either eye). RESULTS: There were 9052 participants from
      211 locations in Oregon and Washington. On initial FDT testing, the right and
      left eye had abnormal results in 18% (1654/9052) and 21% (1918/9052) of
      participants. Of those with abnormal FDT results, approximately 30% of eyes
      reverted to normal on repeat testing. Overall, 13% of participants were screening
      failures. Screening failure was highly associated with age (P<0.001). After
      controlling for age, participants at senior centers (P<0.001) were most likely to
      be screening failures and participants at work sites (P=0.006) were least likely
      to be screening failures when compared with health clinics. CONCLUSIONS: An
      investigator should repeat an initially abnormal FDT result when screening with
      FDT. Age and the location of testing influence the probability of a screening
      failure. Screening in senior centers is most likely to result in screening
      failure. However, only a randomized controlled trial can determine the true
      benefit of FDT screening in these locations.

PMID- 17224755
TI  - Factors affecting the decision to pursue glaucoma fellowship training.
AB  - PURPOSE: To identify factors associated with the choice to pursue glaucoma
      fellowship training by graduating ophthalmology residents. METHODS: An anonymous
      survey was sent to each graduating ophthalmology resident in the United States in
      February 2003. Demographic data and information relating to residency training,
      career goals, and factors influencing career choices were collected from the
      surveys. RESULTS: Surveys were completed by 215 (49.2%) residents, including 135
      (62.8%) who were pursuing fellowships. Among residents undertaking fellowship
      training, 17 (12.6%) selected glaucoma and 118 (87.4%) chose other
      subspecialties. Residents entering glaucoma fellowships performed more glaucoma
      filtering procedures (P=0.006), and they were less likely to publish a paper
      (P=0.05) and have time allocated for research (P=0.04) than residents seeking
      fellowships in other subspecialties. Factors that were rated as less important to
      those choosing glaucoma fellowships included interest in challenging diagnostic
      problems (P=0.009), types of patient problems (P=0.015), an academic career
      (P=0.03), and working with new technology (P=0.04). The decision to pursue
      fellowship training was made later by residents entering glaucoma compared with
      those choosing other subspecialties (P=0.001). CONCLUSIONS: A variety of factors
      affect the decision to pursue fellowship training. There are differences in how
      these factors are weighed among residents seeking fellowships in glaucoma and
      other subspecialties.

PMID- 17224756
TI  - Clinical evaluation of applanation resonance tonometry: a comparison with
      Goldmann applanation tonometry.
AB  - PURPOSE: The purpose of this study was to calibrate and evaluate the precision of
      the new applanation resonance tonometry (ART) in a clinical study designed in
      accordance with the International Standard Organization's requirements. METHODS:
      This was a prospective, randomized, single-center study, where healthy volunteers
      and patients participated. A total of 153 eyes were divided into 3 groups with
      respect to their intraocular pressure (IOP) at screening: <16 mm Hg, 16 to 23 mm
      Hg, and >23 mm Hg. IOP was measured with Goldmann applanation tonometry (GAT) as
      reference method and by ART in both a biomicroscope (ARTBiom) and a handheld
      (ARTHand) setup with a 10-minutes pause between methods. The mean of 6 readings
      was regarded as one measurement value. RESULTS: Mean age of the subjects was 59
      years (range 20 to 87 y). GAT showed a mean IOP of 20.0 mm Hg (range 8.5 to 43.5
      mm Hg, n=153). The precision was 2.07 mm Hg for ARTBiom and 2.50 mm Hg for
      ARTHand, with a significant dependency for age as compared with GAT. Measurement
      order produced a decreasing IOP with a mean of 2.3 mm Hg between the first and
      last method. CONCLUSIONS: The precision obtained in both ARTBiom and ARTHand was
      within the limits set by the International Standard Organization standards for
      tonometers. The standardized procedure and the stability of the biomicroscope
      setup resulted in a slightly better precision as compared with the handheld
      setup. Despite a 10-minutes pause between measurements, the order was a
      significant factor, possibly because the patients were more apprehensive at the
      first measurement.

PMID- 17224757
TI  - Correlation of capsular pseudoexfoliation material and iridocorneal angle pigment
      with the severity of pseudoexfoliation glaucoma.
AB  - PURPOSE: To evaluate the correlation between the amount of pseudoexfoliation
      (PXF) material on the anterior lens capsule, pigment in the iridocorneal angle,
      presenting intraocular pressure (IOP) and severity of glaucoma in patients with
      PXF glaucoma/syndrome. PATIENTS AND METHODS: Anterior lens capsule PXF material
      and iridocorneal pigment of 98 untreated patients with PXF syndrome/glaucoma were
      graded from photographs and correlated with untreated IOP and indices of glaucoma
      severity (cup to disc ratio, and visual field mean deviation, and pattern
      standard deviation). RESULTS: There was a positive statistically significant
      correlation between the iridocorneal angle pigmentation and IOP (P=0.047,
      R2=0.2), but not the indices of glaucoma severity (P>0.13). There was no
      significant correlation between the anterior lens capsule PXF material and IOP or
      the indices of glaucoma severity (P>0.42). The grade of angle pigmentation, but
      not lens PXF, in eyes with IOP >21 mm Hg was significantly higher than in eyes
      with IOP < or =21 mm Hg (P=0.04). CONCLUSIONS: In patients with PXF
      syndrome/glaucoma, gonioscopically identified iridocorneal angle pigmentation
      correlates more strongly with presenting IOP than the amount of PXF material on
      the anterior lens capsule.

PMID- 17224758
TI  - Travoprost 0.004% with and without benzalkonium chloride: a comparison of safety
      and efficacy.
AB  - PURPOSE: To compare the safety and efficacy of travoprost 0.004% without
      benzalkonium chloride (BAC) to that of the marketed formulation of travoprost
      0.004% in patients with open-angle glaucoma or ocular hypertension. METHODS: The
      study was a double-masked, randomized, parallel group, multicenter,
      noninferiority design. Adult patients with open-angle glaucoma or ocular
      hypertension with qualifying intraocular pressure (IOP) on 2 eligibility visits
      received either travoprost 0.004% with BAC (n=346), or travoprost 0.004% without
      BAC (n=344) dosed once-daily each evening. Patients were followed for a period of
      3 months. IOP measurements at 8 AM, 10 AM, and 4 PM were taken at study visits on
      week 2, week 6, and month 3. RESULTS: Mean IOP reductions, across all 9 study
      visits and times ranged from 7.3 to 8.5 mm Hg for travoprost 0.004% without BAC
      and from 7.4 to 8.4 mm Hg for travoprost 0.004% with BAC. Statistical equivalence
      was also demonstrated for the comparison of mean IOP changes; 95% confidence
      limits were within +/-0.8 mm Hg at 9 of 9 study visits and times in both the per
      protocol and intent-to-treat data sets. Adverse events and the number of patients
      discontinued owing to adverse events were similar for both treatment groups.
      Adverse events due to hyperemia occurred in 6.4% and 9.0% of patients treated
      with travoprost 0.004% without BAC and travoprost 0.004% with BAC, respectively.
      CONCLUSION: Travoprost 0.004% without BAC is equivalent to travoprost 0.004% with
      BAC in both safety and efficacy.

PMID- 17224759
TI  - A clinical and molecular genetic study of Egyptian and Saudi Arabian patients
      with primary congenital glaucoma (PCG).
AB  - PURPOSE: To undertake mutation screening of cytochrome P4501B1 (CYP1B1, OMIM
      601771) and myocilin (MYOC, OMIM 601652) genes in Egyptian and Saudi Arabian
      patients with primary congenital glaucoma (PCG). PATIENTS AND METHODS: A clinical
      and molecular genetic study was performed on 11 Egyptian and Saudi Arabian
      patients with PCG. Clinical diagnosis was confirmed by slit lamp biomicroscopy,
      gonioscopy, measurement of intraocular pressure, and corneal diameter. The coding
      regions of CYP1B1 and MYOC genes were amplified by polymerase chain reaction for
      all affected subjects. Direct sequence analysis was performed to search for
      sequence alterations. Haplotype analysis and genotype/phenotype correlation were
      carried out. RESULTS: Three CYP1B1 mutations were identified in 5 PCG patients
      (45.4%) of which 2 were novel (homozygous E173K and heterozygous N498D) and the
      third (G61E) had previously been reported. In addition 10 single nucleotide
      polymorphisms were identified in CYP1B1 and MYOC genes of which 2 were novel.
      However, no pathologic changes in either of the genes were detected in the
      remaining 6 patients. CONCLUSIONS: This is the first report of molecular genetic
      analysis of PCG in the Egyptian population in which 2 novel mutations have been
      identified. It is possible that these mutations are specific to this population
      and may lead to alterations in the protein structure encoded by the gene.
      Patients with no mutations in the screened genes may have mutations in genes yet
      to be identified.

PMID- 17224760
TI  - Changes in scanning laser polarimetry before and after laser capsulotomy for
      posterior capsular opacification.
AB  - PURPOSE: To investigate changes in scanning laser polarimetry with variable
      corneal compensation (GDx-VCC) parameters caused by posterior capsular
      opacification (PCO). METHODS: In this comparative case-control series, 20 eyes
      due to undergo YAG laser capsulotomy for PCO were recruited. GDx-VCC was
      performed before and after laser capsulotomy, and digital photographs were taken
      of the PCO to assess their severity and type. The other eye of each subject was
      used as the control group. RESULTS: Typical scan score was significantly improved
      after laser from 33 to 55.1 (P=0.001; n=19) and TSNIT score was significantly
      lower, dropping from 62.3 to 58.9 (P=0.03; n=19). There was no change in the
      nerve fiber index. All parameters in the control group remained unchanged except
      the Q-score which rose from 8.1 to 8.8 (P=0.05; n=16). There was no correlation
      between severity of PCO or the pearly/fibrous nature and the change in parameter
      values. CONCLUSIONS: We conclude that in subjects being considered with GDx-VCC,
      the presence of visually significant PCO may introduce artifact as judged by the
      typical scan score.

PMID- 17224761
TI  - The risk of glaucoma in pseudoexfoliation syndrome.
AB  - PURPOSE: To determine the conversion rate of pseudoexfoliation syndrome (PEX) to
      pseudoexfoliative glaucoma or treated ocular hypertension. METHODS: Retrospective
      community-based study of newly diagnosed cases of PEX syndrome in all residents
      of Olmsted County, Minnesota between 1976 and 1991. The end point was considered
      the initiation of therapy, which included patients with glaucoma (optic disc
      damage or visual field defects), or with elevated intraocular pressure (IOP) >21
      mm Hg in the presence of risk factors; the subsequent development of damage in
      the latter group was also determined. RESULTS: Two hundred fifty-five patients
      (318 eyes) had newly diagnosed PEX over the 15-year interval. Mean age was 73+/
      10 years; 78% (199/255) were female. Of all PEX patients, 16% were placed on
      therapy at the time of initial diagnosis of PEX. In the remaining PEX patients,
      the probability of being placed on therapy was 44% at 15 years. Bilateral PEX was
      present in 25% at initial diagnosis and developed in another 29% by 15 years. Of
      those not placed on therapy, 16% (23/142) had IOP increase 5+ mm Hg during follow
      up, with 11% (16/142) reaching 22 mm Hg or more. The strongest risk factors for
      converting to therapy were IOP at initial diagnosis of PEX and bilateral
      involvement. CONCLUSIONS: In a geographically defined population of PEX patients,
      16% required treatment upon presentation. Of the remaining PEX patients, 44%
      received therapy over the next 15 years.

PMID- 17224762
TI  - Gender variation in ocular biometry and ultrasound biomicroscopy of primary angle
      closure suspects and normal eyes.
AB  - PURPOSE: To compare A-scan biometry and ultrasound biomicroscopy of primary angle
      closure suspects (PACS) with age-matched normal Indian eyes. PATIENTS AND
      METHODS: Subjects with primary angle closure suspects (n=57 eyes) and normal eyes
      (n=57 eyes) underwent A-scan biometry and ultrasound biomicroscopy. Anterior
      chamber depth (ACD), anterior chamber angle (ACA), axial length (AXL), lens
      thickness, relative lens position (RLP), central corneal thickness (CCT), angle
      opening distance 500, trabecular-ciliary process distance (TCPD), iris-ciliary
      process distance, iris thickness, and scleral-ciliary process angle were
      measured. The subjects were divided into males, females, and combined groups for
      analysis. The parameters were compared using independent sample t test with
      Bonferroni correction for multiple comparisons. RESULTS: In the combined group,
      the PACS subjects presented a significantly low ACD, AXL, CCT, AOD500, TCPD, ACA
      (P<0.001), and RLP (P=0.04). In males, RLP was anterior (P=0.002) and in females,
      the lens thickness (P<0.001) was significantly thicker among the PACS group.
      CONCLUSIONS: ACD, AXL, CCT, TCPD, ACA, and angle opening distance 500 of the PACS
      group were significantly lower than in normals. In females, the lens in PACS was
      thicker than in normals. Lens in males was more anterior-placed in PACS group
      than in normals.

PMID- 17224763
TI  - Model of pulsatile-flow of aqueous humor through the iris-lens canal.
AB  - PURPOSE: To present a model of pulsatile-flow of aqueous humor from posterior
      (PC) to anterior chamber (AC) and to analyze the sensitivity of this novel model
      in detecting typical high risk conditions predisposing to pupillary block.
      METHODS: The model assumes noncontinuous flow of aqueous through the iris-lens
      canal. Aqueous that fills the canal will be ejected toward the AC-side of the
      canal at certain time intervals, and between 2 events of aqueous ejection there
      is no actual flow through this canal. Pupillary pumping rate (PPR) was calculated
      from the aqueous flow rate and the calculated volume of iris-lens canal. RESULTS:
      PPR values were generated by incorporating pupillary diameter (1 to 8 mm),
      aqueous flow rate (1 to 2.5 microL/min), and iris-lens canal width (0.5 to 2 mm)
      and height (3-9 microm) in numerical experimentation with the present model. PPR
      showed inverse dependence on iris-lens canal height and pupillary diameter and
      was directly proportional to aqueous flow rate, in agreement with the steady-flow
      model. However, contrary to the steady-flow model, PPR showed inverse dependence
      on iris-lens canal width and predicted the anticipated PC-AC pressure gradient
      changes at simulated light-dark transition in eyes of patients with clinically
      narrow angles and ultrasound biomicroscopy evidenced pupillary block.
      CONCLUSIONS: Upon the incorporation of real ultrasound biomicroscopy measurements
      in numerical experimentations with both models, the present pulsatile-flow model,
      contrary to the steady-flow model, showed good predictability of PC-AC pressure
      gradient changes in a typical condition predisposing to pupillary block.

PMID- 17224764
TI  - Prospective evaluation of factors associated with post-LASIK corneal
      birefringence with scanning laser polarimetry.
AB  - PURPOSE: To identify factors that affect corneal birefringence, such as the
      corneal polarization axis (CPA) and corneal polarization magnitude (CPM), after
      laser in situ keratomileusis (LASIK) using scanning laser polarimetry with a
      variable corneal polarization compensator. METHODS: The CPA and CPM from 42
      patients (42 eyes) who underwent LASIK and 24 normal untreated subjects (24 eyes)
      were measured 1 week before and 1 week after LASIK. Changes in the CPA and CPM
      after LASIK were studied using Student t test and Pearson correlation
      coefficient. RESULTS: In the LASIK group, the post-LASIK CPA and CPM
      significantly changed, whereas both values did not change in normal subjects.
      Among 5 candidate factors [preoperative CPA (pre-CPA), preoperative CPM (pre
      CPM), age, change in corneal curvature, and ablation depth], the change in CPA
      was significantly correlated with the pre-CPA (r=-0.793) and pre-CPM (r=0.339).
      The change in CPM was correlated with the pre-CPA (r=-0.455) and pre-CPM (r=
      0.411). Over 83% case of postoperative corneal birefringence can be explained by
      only 2 parameters with regression analysis. CONCLUSIONS: The pre-CPA and pre-CPM
      are strongly associated with LASIK-induced changes in CPA and CPM. Variations in
      age, changes in corneal curvature, and ablation depth do not contribute to
      changes in either parameter.

PMID- 17224765
TI  - Classifying patterns of localized glaucomatous visual field defects on automated
      perimetry.
AB  - AIM: To classify the classic patterns of glaucomatous visual field defects on
      automated perimetry and to study their proximity to fixation. STUDY DESIGN: Cross
      sectional observational study. MATERIALS AND METHODS: About 1120 full threshold
      30-2 reliable visual fields of glaucoma patients were analyzed by 2
      glaucomatologists. Classically described patterns of visual field defects were
      identified on the pattern deviation plot and definitions proposed. Interreader
      agreement between 3 independent (not involved in the classification) readers was
      determined. Proximity to fixation of the different patterns was assessed.
      RESULTS: Interreader agreement with 3 readers was found to be 93% or more between
      any 2 readers using the present system of classification. Central fixation was
      seen to be involved in 45% of the glaucomatous visual field defects studied
      overall. CONCLUSIONS: The proposed definitions of topographical glaucomatous
      field defects based on the pattern deviation probability plot are simple to use
      in clinical practice with good interreader agreement.

PMID- 17224766
TI  - The effect of contact lens induced corneal edema on Goldmann applanation
      tonometry measurements.
AB  - AIM: To determine the effect of small increases in corneal hydration on the
      accuracy of Goldmann applanation tonometry estimates of intraocular pressure
      (IOP). MATERIALS AND METHODS: Twenty-five young healthy subjects presented on 3
      separate days approximately 1 week apart. On 2 visits, subjects were required to
      wear a hydrogel contact lens with either a center thickness of 0.3 and 0.7 mm
      (HEMA 38% water content, parallel surface curve) in 1 eye only under closed-eye
      conditions for 2 hours to induce corneal swelling. The third visit acted as a
      control. IOP, corneal thickness, and corneal curvature were measured in both eyes
      before and after contact lens wear on all visits. RESULTS: There was a
      statistically significant increase in corneal thickness of 40.2+/-14.4 microm
      (P<0.001) and 41.9+/-16.4 microm (P<0.001) after wearing the 0.3 and 0.7 mm thick
      contact lenses, respectively (2-tailed paired t test). There was an increase in
      IOP of 2.8+/-2.2 mm Hg (P<0.001) after wearing the 0.3 mm thick contact lens, and
      a statistically insignificant difference of 1.3+/-3.0 mm Hg (P=0.058) after
      wearing the 0.7 mm thick contact lens (2-tailed paired t test). There was a
      statistically significant Pearson correlation between the change in corneal
      thickness and the change in IOP after lens wear (r=0.500, P<0.001, 0.3 mm lens
      and r=0.399, P<0.001, 0.7 mm lens). The corneal hydration-induced measurement
      error was 0.46 mm Hg per 10 microm change in corneal thickness (0.3 mm lens) and
      0.35 mm Hg per 10 microm change in corneal thickness (0.7 mm lens). CONCLUSION: A
      small increase in corneal hydration and thickness may cause a clinically
      significant overestimation of IOP when measured using Goldmann applanation
      tonometry.

PMID- 17224767
TI  - Relationship of cerebral blood flow and central visual function in primary open
      angle glaucoma.
AB  - PURPOSE: To investigate the relations between middle cerebral artery (MCA) blood
      flow velocities and central visual function measured by foveal cone
      electroretinograms (ERG) and visual field. METHODS: Fifteen primary open-angle
      glaucoma patients were recruited. The eye with the more severe visual field
      defect (full threshold 24-2) and/or optic disc damage was chosen. Measurements
      included brachial arterial pressure, heart rate, visual acuity (logMAR), contrast
      sensitivity (CSV-1000), central visual field (Humphrey SITA 10-2), foveal cone
      ERG, and transcranial Doppler. Pearson correlation coefficients were estimated to
      assess the strength of the linear relationship between the MCA flow velocity and
      the other measured parameters. RESULTS: Visual field was successfully completed
      in 12 eyes. We were unable to obtain ERG responses and MCA velocity readings for
      1 patient. A significant correlation was observed between MCA mean flow velocity
      and focal cone ERG amplitude [r=0.69, n=13, confidence interval (CI) 0.22, 0.90,
      P=0.009], but correlation between mean foveal cone ERG implicit time and middle
      cerebral was not statistically significant (r=0.011, n=13, CI 0.47, 0.63). A
      significant correlation was also observed between MCA mean flow velocity and mean
      sensitivity (r=0.76, n=12, CI 0.32, 0.93, P=0.005), and mean defect (r=0.73,
      n=12, CI 0.28, 0.92, P=0.007) of the central visual field, logMAR visual acuity
      (r=0.57, n=14, CI 0.05, 0.84, P=0.036), and contrast sensitivity (r=0.61, n=13,
      CI 0.09, 0.87, P=0.027). CONCLUSIONS: Our findings suggest that in certain
      primary open-angle glaucoma patients diminished central visual function may be
      one manifestation of widespread cerebrovascular insufficiency.

PMID- 17224768
TI  - Large diurnal variation of intraocular pressure despite maximal medical treatment
      in juvenile open angle glaucoma.
AB  - PURPOSE: To report the clinical significance of large fluctuations in intraocular
      pressure (IOP) and the effect of trabeculectomy on diurnal IOP variations in 2
      cases of maximally medically treated juvenile open angle glaucoma (JOAG).
      PATIENTS AND METHODS: A 24-hour IOP monitoring was performed before and after
      trabeculectomy on both eyes of 2 JOAG patients-one with transiently blurred
      vision early in the morning, the other with progression of visual field defect
      despite apparently well-controlled IOP. The patients' optic discs were scanned
      with Heidelberg retina tomograph (HRT) during peak and trough IOPs before
      trabeculectomy. RESULTS: Preoperatively, diurnal IOP varied widely up to 20/19
      (OD/OS) mm Hg in case 1 and up to 16/22 (OD/OS) mm Hg in case 2, even though both
      patients were using 4 different types of antiglaucoma eye drops. Peak IOP was
      associated with temporary blurring of vision and mild corneal edema in 1 patient
      (case 1). Heidelberg retina tomograph revealed a deepening of the optic cup and a
      resultant narrowing of the neuroretinal rim at peak IOP in this patient; this was
      not detected in the second patient who had tilted optic discs. After
      trabeculectomy, diurnal IOP fluctuations were reduced to 4-6/2-4 (OD/OS) mm Hg in
      case 1 and to 6-7/3-7 (OD/OS) mm Hg in case 2, with a decrease in peak IOPs as
      well. CONCLUSIONS: Wide diurnal variation should be suspected in JOAG patients,
      even when receiving maximal medical treatment; this is especially important in
      cases with temporary blurred vision and/or progression of visual field defect
      despite apparently well-controlled IOP. Trabeculectomy was more effective in
      reducing diurnal IOP variation than medical treatment.

PMID- 17224769
TI  - 25-gauge vitrectomy to treat ocular complications of familial amyloid
      polyneuropathy.
AB  - PURPOSE: Secondary glaucoma and vitreous opacity with amyloid fibrils are the 2
      major ocular complications of familial amyloid polyneuropathy (FAP). We
      investigated the feasibility of 25-gauge vitrectomy in excising the opaque
      vitreous into eyes that had already undergone trabeculectomy. METHODS: For the
      purpose of vision recovery, 25-gauge vitrectomy was performed in 2 eyes with
      vitreous amyloidosis. Both eyes had undergone trabeculectomy to treat glaucoma
      secondary to FAP. The survival of the filtration bleb after 25-gauge vitrectomy
      was also evaluated. RESULTS: Vision improved dramatically on the next day after
      the 25-gauge vitrectomy that causes minimal damage to the eye. No apparent
      complications including failure of the filtration bleb have been observed
      throughout the follow-up period of 6 months. CONCLUSIONS: 25-gauge vitrectomy has
      a potential to become a therapy of choice to excise opaque vitreous with amyloid
      fibrils in FAP, especially in the glaucomatous eyes that have already undergone
      trabeculectomy.

PMID- 17224770
TI  - Human amniotic membrane transplantation for tube exposure after glaucoma drainage
      device implantation.
AB  - We present a case of conjunctival melting over the tube of a glaucoma shunt,
      which was successfully repaired with amniotic membrane transplantation.

PMID- 17224771
TI  - Underuse of generic medications.

PMID- 17224772
TI  - Use of generic cardiovascular medications by elderly Medicare beneficiaries
      receiving generalist or cardiologist care.
AB  - BACKGROUND: Elderly Medicare beneficiaries can reduce out-of-pocket spending and
      increase their options for low-cost Medicare Part D plans by using generic drugs.
      Physicians play a key role in determining use of generics and specialty may be a
      particularly influential factor. OBJECTIVES: We sought to compare generic
      cardiovascular drug use by older adults receiving cardiologist and generalist
      care. RESEARCH DESIGN: We undertook a cross-sectional analysis of data from the
      nationally representative Medicare Current Beneficiary Survey. Included were
      community-dwelling adults 66 years of age or older with hypertension, coronary
      disease, or congestive heart failure, one or more Medicare Part B claims for
      outpatient visits with generalists (internist or family practitioner) or
      cardiologists, using one or more cardiovascular drug available in both brand-name
      and generic formulations (n = 1828). MEASURES: The primary outcome was use of one
      or more generic medication aggregated across 5 drug classes: beta-blockers,
      thiazides, calcium channel blockers (CCB), angiotensin-converting enzyme (ACE)
      inhibitors, and alpha1-adrenergic receptor antagonists. Within-class generic use
      also was examined. The main independent variable was cardiologist (20.7%) versus
      generalist-only care (79.3%). RESULTS: In the aggregate, fewer individuals under
      cardiologist care used generics compared with generalist-only care (75% vs. 81%,
      P = 0.03; adjusted relative risk 0.89, 95% confidence interval = 0.79-0.99).
      Overall use of generic beta-blockers was 86.6%; thiazides, 92.0%; ACE inhibitors,
      59.0%; CCB, 55.5%; alpha-blockers 47.7%. In adjusted analysis, generic CCB use
      occurred 34% less often among cardiologist versus generalist-only patients.
      CONCLUSIONS: Older patients of generalists and, to a greater extent,
      cardiologists, often use brand-name drugs when generic equivalents are available.
      Promoting generic prescribing among specialists and generalists may increase
      opportunities for patients and third-party payers to reduce spending on
      prescription drugs.

PMID- 17224773
TI  - The excess medical cost and health problems of family members of persons
      diagnosed with alcohol or drug problems.
AB  - BACKGROUND: Having a family member with substance use problems affects family
      functioning, which may lead to increased medical problems and increased health
      care utilization and costs in the other family members. AIM: We sought to
      estimate the excess medical costs and prevalence of diagnosed health conditions
      of family members of persons with an alcohol or drug diagnosis (AOD) compared
      with the family members of similar persons without an AOD. METHODS: Using a large
      health plan's administrative databases, we identified persons who received an AOD
      between 2001 and 2004 and a similar group of persons with no AOD during that
      time. Using a hierarchical linear mixed model, we compared the cost and
      utilization of the family members of the AOD and non-AOD patients in the 2 years
      prior to the AOD patient's first AOD. Using logistic regression, we determined
      whether the family members of patients with AODs were more likely than comparison
      family members to be diagnosed with medical conditions. RESULTS: Family members
      of patients with AODs had greater health care costs than comparison family
      members in the second year before the index date (490 dollars) and in the year
      before the index date (433 dollars). This was the case for both adult and child
      family members. They also were more likely to be diagnosed with many medical
      conditions, especially substance abuse and depression. CONCLUSIONS: Family
      members of patients with AODs have greater health care costs and are more likely
      to be diagnosed with a number of medical conditions than family members of
      similar persons without an AOD.

PMID- 17224774
TI  - Did the Medicare inpatient rehabilitation facility prospective payment system
      result in changes in relative patient severity and relative resource use?
AB  - BACKGROUND: The Centers for Medicare and Medicaid Services implemented a
      prospective payment system (PPS) in 2002 for care provided by inpatient
      rehabilitation facilities (IRFs) to Medicare beneficiaries. OBJECTIVE: We sought
      to examine changes in the composition of Medicare beneficiaries in IRFs by
      examining the percentages of patients having worse functional or health status
      than the average for their payment groups (relative severity) and of patients
      having greater cost or longer length of stay than the average for their payment
      groups (relative resource use) before versus after IRF PPS; to examine whether
      observed changes in relative resource use were expected given predicted changes;
      and to explore whether these effects varied by IRF Medicare volume. METHODS: In
      an observational study of indicators of Medicare beneficiary relative severity
      and relative resource use, we studied cases paid for by Medicare during 1999 and
      2002 having an acute care stay preceding their IRF stay (n = 363,542 in 1999 and
      446,002 in 2002). RESULTS: Similar percentages of cases had longer than expected
      lengths of stay, greater-than-expected costs per case, and worse-than-expected
      functional status pre- versus post-IRF PPS. Cases under the IRF PPS had lower
      predicted probabilities of death 150 days after admission. Although predicted
      relative resource use remained steady, observed relative resource use decreased
      after IRF PPS. CONCLUSIONS: IRF patient composition has not changed meaningfully
      for Medicare beneficiaries, but patients within payment groups are being provided
      less care, which could be attributable to the IRF PPS, existing trends in
      decreasing length of stay, or both.

PMID- 17224775
TI  - Does the patient's payer matter in hospital patient safety?: a study of urban
      hospitals.
AB  - BACKGROUND: Previous studies have documented that hospitals decrease costs in
      response to reimbursement cutbacks. However, research concerning how this may
      affect quality of care has produced mixed results. Until recently, the ability to
      study changes in patient safety and payment has been limited. OBJECTIVE: The
      objective of the study was to determine whether changes in 4 hospital patient
      safety indicator (PSI) rates are related to changes in the generosity of payers
      over time. DATA AND METHODS: Study data are drawn from 1995-2000 hospital
      discharges in 11 states in the Agency for Healthcare Research and Quality
      Healthcare Cost and Utilization Project State Inpatient Database. Following the
      same organizations over time, we estimate hospital fixed-effects regression
      models of the association of payer-specific time and post Balanced Budget Act
      (BBA) payment changes with risk-adjusted hospital PSI rates controlling for
      patient, organizational, and market characteristics. Four PSIs relevant to a
      large number of patients and hospitals that reflect general care processes are
      studied. RESULTS: The time trend during 1995-2000 is consistently significantly
      positive for private and Medicare hospital PSI rates. Thus, after controlling for
      patient characteristics and organizational and market factors, performance
      worsened. The trend is less consistent for Medicaid and does not exist for self
      pay hospital PSI rates. After adjusting for multiple comparisons, we also find
      that the Medicare trend is fairly consistently higher than that of the other
      payers. In contrast, there is a less consistent BBA effect, especially for
      Medicare.

PMID- 17224776
TI  - The impact of managed care enrollment on emergency department use among children
      with special health care needs.
AB  - BACKGROUND: Many states recently have experimented with managed care as a way
      both to control costs and to enhance continuity of care in their publicly
      financed programs. A few states have applied managed care models to the care of
      chronically ill children. One marker for the effects of managed care is changes
      in use of the emergency department (ED). OBJECTIVE: We sought to determine
      whether a managed care program can reduce ED use for children with chronic health
      problems. SUBJECTS: We studied chronically ill children who were dually enrolled
      in Michigan's Title V program for children with special health care needs and
      Medicaid and who were enrolled in a managed care option at some time during the
      study period. The managed care model emphasized care coordination and did not
      include strong financial incentives for utilization and cost control. Sample
      consisted of 8580 person-months. METHOD: We used a fixed-effect negative binomial
      Poisson regression model to compare ED use before and after joining a managed
      care plan to test whether managed care use was associated with reduced likelihood
      of ED use. RESULTS: Managed care enrollment was associated with a 23% reduction
      in the incidence of ED use among children dually enrolled in Medicaid and Title
      V. CONCLUSIONS: A managed care model is associated with statistically significant
      and substantive reductions in observed use of ED care within an important
      population of children facing chronic illness.

PMID- 17224777
TI  - Caregivers' ratings of access: do children with special health care needs fare
      better under fee-for-service or partially capitated managed care?
AB  - OBJECTIVE: The objective of this study was to evaluate how enrollment in a
      partially capitated managed care (MC) option versus the fee-for-service (FFS)
      system affects caregivers' ratings of dimensions of access to services among
      children with special health care needs (SHCN). SUBJECTS: The data were collected
      from telephone interviews during the summer and fall of 2002 with a random sample
      of 1088 caregivers of children with SHCN who qualified for Supplemental Security
      Income and therefore were enrolled the Medicaid program for children with SHCN in
      the District of Columbia. RESEARCH DESIGN: We used a 2-step procedure in which we
      first estimated plan choice and then constructed a selectivity correction to
      control for the potential selection bias linked to plan choice. We estimated the
      second stage equations predicting caregiver's ratings of dimensions of access as
      a function of the selectivity correction, the plan choice dummy variable and
      other exogenous variables. RESULTS: After controlling for the potential selection
      bias linked to plan choice and other confounding factors, we find that caregivers
      of children in FFS are significantly more likely than caregivers of children
      enrolled in the partially capitated MC plan to rate the following dimensions of
      access as either fair or poor: "access to specialists' care" (P < 0.01), "access
      to emergency room care" (P < 0.01), "convenience of the doctor's office" (P <
      0.01), and "waiting time between making the appointment actual visit" (P < 0.05).
      CONCLUSIONS: We attribute these differences in caregivers' ratings of dimensions
      of access that exist between partially capitated MC and FFS enrollees to case
      management and care coordination services along with higher fees paid for
      pediatrician's and specialists' services available under MC option.

PMID- 17224778
TI  - Trends in treatment costs for localized prostate cancer: the healthy screenee
      effect.
AB  - OBJECTIVE: We sought to obtain estimates of trends in initial treatment costs
      during the prostate-specific antigen (PSA) era that account for the changing
      patient case-mix associated with screening. SUBJECTS: We used reimbursement
      claims for Medicare-eligible subjects diagnosed with nonmetastatic prostate
      cancer between 1991 and 1999. Patients were grouped by initial treatment, with
      17,846 receiving radical prostatectomy (RP), 25,933 receiving external beam
      radiotherapy (XRT), and 4525 receiving brachytherapy (BT). METHODS: Cancer
      attributable costs were computed by subtracting noncancer costs from total
      Medicare reimbursements among newly diagnosed cancer patients. Noncancer costs
      were estimated in 2 ways: (1) average costs among age-matched, cancer-free
      control subjects (control method) and (2) projections based on claims from
      subjects before diagnosis (prediagnosis method). Adjusted annual percent change
      in cancer-attributable costs was calculated using multivariate generalized linear
      models. RESULTS: Noncancer costs increased at a much lower rate among men prior
      to diagnosis (3.8% annually) than among the general Medicare population (10.9%).
      The 2 approaches yielded different results; RP costs declined by 2.4% annually
      (prediagnosis method) versus 6.2% (control method); XRT costs declined by 1.5%
      versus 5.8%; and BT costs declined by 4.1% versus 8.3%. CONCLUSIONS: Because of
      self-selection of PSA screening, men diagnosed with prostate cancer today are now
      healthier overall than men in the general population and are considerably
      healthier than men diagnosed previously. Estimates of cancer-attributable costs
      that do not account for this healthy selection effect are likely to be biased.
      Declines in cancer-attributable treatment costs are evident even after accounting
      for a healthy screenee effect, suggesting that there has been a real reduction in
      cancer treatment costs.

PMID- 17224779
TI  - Trends in colonoscopy for colorectal cancer screening.
AB  - BACKGROUND: A major health priority is to increase colorectal cancer screening,
      and colonoscopy has become an increasingly important method of screening. The
      Medicare program began coverage for colonoscopy for average risk individuals in
      2001. OBJECTIVES: We sought to examine whether overall colorectal cancer
      screening increased over time and whether these increases were a result of
      increased utilization of all methods or a result of greater use of colonoscopy
      but reduced use of other methods, whether the enactment of Medicare coverage was
      associated with an increase in colonoscopy among Medicare enrollees, and whether
      these trends equally affected subpopulations. METHODS: We used nationally
      representative data from the 2000 and 2003 National Health Interview Surveys and
      analyzed data using used chi, difference-in-differences tests, and logistic
      regression analyses to examine whether screening rates differed between 2000 and
      2003. RESULTS: The percentage of individuals being screened for colorectal cancer
      using any method increased modestly from 2000 to 2003 (3%), with increases a
      result of increased use of colonoscopy and a reduction in the use of other
      methods. Increases in colonoscopy use were significant among all populations
      except the insured, non-Medicare population with low incomes. Among Medicare
      enrollees with high/middle incomes, colonoscopy use increased 14% from 2000 to
      2003 compared with an increase of only 7% among low-income groups, which was a
      significant difference (P < 0.01). Similarly, among insured, non-Medicare
      enrollees with high/middle incomes, colonoscopy use increased 11% from 2000 to
      2003 compared with an increase of only 4% among low-income groups, which also was
      a significant difference (P < 0.01). CONCLUSIONS: Colorectal cancer screening
      utilization increased modestly from 2000 to 2003, with the increases that
      primarily were the result of increased colonoscopy use. Increases in colonoscopy
      use, however, were primarily among high/middle income groups. Although Medicare
      coverage may have indirectly facilitated the increase in colonoscopy, we could
      not determine that coverage directly increased screening rates. Screening rates
      remain modest and lower income individuals continue to be screened less. Topics
      for future research include approaches to facilitating screening among low-income
      individuals and evaluating the impact of policy coverage decisions.

PMID- 17224780
TI  - Physician practice revenues and use of information technology in patient care.
AB  - OBJECTIVES: Although information technology (IT) may improve efficiency and
      quality of patient care, the adoption of clinical IT by physicians has been
      limited. This study investigates the relationships between physician practice
      revenue and use of clinical IT. RESEARCH DESIGN: We undertook a cross-sectional
      analysis of data on 6849 U.S. physicians in physician-owned practices who
      responded to the 2000-2001 Community Tracking Study Physician Survey. Physician
      practice revenues, measured as the percentage of total revenues, is defined along
      2 dimensions: type (capitation, noncapitated managed care, or fee-for-service)
      and source (Medicare, Medicaid, or private/other). Analyses were adjusted for
      physician and practice characteristics and geographic location. MEASURES: The
      proportion of physicians using IT for 5 functions of patient care: treatment
      guidelines, formularies, patient notes or lists, electronic prescriptions, and
      data exchange with other physicians. RESULTS: Practice revenues are associated
      with differences in physicians' use of IT in patient care. Above-average Medicaid
      revenue was associated with 20% higher use of IT overall (incidence density ratio
      = 1.20, 95% confidence interval [CI] = 1.12-1.30). Above-average capitation
      revenue corresponds to higher use of IT overall (incidence density ratio = 1.10,
      95% CI = 1.02-1.19) and greater odds of using IT for guidelines (odds ratio =
      1.26, 95% CI = 1.05-1.53). Above-average noncapitated managed care revenue,
      however, has no apparent relationship with IT use. CONCLUSIONS: Differences in
      the type and source of physician revenues were associated with differences in the
      use of IT in patient care in 2000-2001. The relationships between practice
      revenues and IT use varied across clinical IT functions.

PMID- 17224781
TI  - The effect of screening and brief intervention for risky drinking on health care
      utilization in managed care organizations.
AB  - OBJECTIVE: We sought to estimate the effect of screening and brief intervention
      (SBI) for risky alcohol use on the health care utilization of risky drinkers in 4
      managed care organizations. RESEARCH DESIGN: A quasi-experimental group design
      was implemented in which 12 participating primary care clinics randomly were
      assigned to 1 of 3 study conditions. In one condition, physicians, physician
      assistants, and nurse practitioners delivered the brief intervention. In another
      condition, midlevel professionals (usually nurses) performed the brief
      intervention. In the third condition, SBI was not performed. Using administrative
      claims data, we estimated the effect of SBI on individual-level annual days of
      total and inpatient health care utilization; annual outpatient visits; annual
      emergency room visits; and annual visits related to alcohol, drug, or mental
      health conditions. Negative binomial regression models were used to control for
      other factors that may affect health care utilization. RESULTS: Across all
      categories of care, the pre- to postintervention change in average health care
      utilization among risky drinkers in the intervention clinics was not
      significantly different from that of risky drinkers in the comparison clinics.
      CONCLUSIONS: Our findings suggest that there is no effect of SBI on the health
      care utilization of risky drinkers in the year following the intervention.
      Although SBI does not appear to reduce health care utilization, previous studies
      find that it significantly reduces the alcohol consumption of risky drinkers.
      Because these reductions presumably improve patients' overall health and well
      being, managed care organizations may still find it beneficial to implement SBI
      on a broad scale.

PMID- 17224782
TI  - Outpatient mental health utilization among commercially insured individuals: in-
      and out-of-network care.
AB  - OBJECTIVE: This study examined the rates and correlates of out-of-network
      outpatient mental health specialty care. RESEARCH DESIGN: Using administrative
      data from a large insurer, we examine the frequency of out-of-network
      utilization, analyze demographic and clinical characteristics of individuals
      receiving out-of-network care, and examine the types of service provided out-of
      network. RESULTS: Out-of-network outpatient mental health care was received by
      15.4% of adults who used outpatient mental health services, with 11.8% of adult
      outpatient mental health users receiving only out-of-network care and 3.6%
      receiving both in-network and out-of-network care. Out-of-network users received
      significantly more outpatient mental health care than individuals receiving only
      in-network mental health care. Rates of out-of-network psychotherapy services
      were substantially greater than for other commonly provided mental health
      services. CONCLUSION: A significant number of patients covered under this insurer
      received their outpatient mental health care out-of-network. This is most
      pronounced for individuals receiving psychotherapy. Further information is needed
      to improve our understanding of who seeks care from out-of-network providers and
      why as well as the effect of such care on clinical outcomes.

PMID- 17224784
TI  - Glycogen synthase kinase 3beta as a target for the therapy of shock and
      inflammation.
AB  - After the discovery that glycogen synthase kinase (GSK) 3beta plays a fundamental
      role in the regulation of the activity of nuclear factor kappaB, a number of
      studies have investigated the effects of this protein kinase in the regulation of
      the inflammatory process. The GSK-3beta inhibition, using genetically modified
      cells and chemically different pharmacological inhibitors, affects the regulation
      of various inflammatory mediators in vitro and in vivo. Insulin, an endogenous
      inhibitor of GSK-3 in the pathway leading to the regulation of glycogen synthase
      activity, has recently been clinically used in the therapy for septic shock. The
      beneficial anti-inflammatory effects of insulin in preclinical and clinical
      studies could possibly be due, at least in part, to the inhibition of GSK-3 and
      not directly correlated to the regulation of blood glucose. We describe the
      latest studies describing the effects of GSK-3 inhibition as potential target of
      the therapy for diseases associated with inflammation, ischemia/reperfusion, and
      shock.

PMID- 17224785
TI  - The role of the intestinal barrier in the pathogenesis of necrotizing
      enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is the leading cause of death from
      gastrointestinal disease in neonates and is increasing in frequency because of
      recent advances in neonatal care. NEC develops in a stressed preterm infant in
      the setting of intestinal barrier disruption, systemic inflammation, and leads
      to, multisystem organ failure. The intestinal barrier lies at the interface
      between microbes within the intestinal lumen and the immune system of the host,
      and has both immunological and mechanical components. These components serve to
      protect the host from invading pathogens and, at the same time, provide a surface
      area for nutrient absorption. Factors that lead to impairments in the function of
      the intestinal barrier may predispose the host to the invasion of gut-derived
      microbes and to the development of systemic inflammatory disease. This process,
      termed "bacterial translocation," may be compounded during instances in which the
      mechanisms that regulate the repair of the intestinal barrier are disrupted.
      Bacterial translocation is of particular concern to the newborn patient, in which
      immaturity of the mechanical barrier and incomplete development of the host
      immune system combine to render the host at particular risk for the development
      of intestinal inflammation. This review will serve to provide an overview of
      recent evidence regarding the components of the intestinal barrier, and the
      mechanisms by which disruptions in barrier function may contribute to the
      pathogenesis of NEC.

PMID- 17224786
TI  - Post-traumatic hypotension: should systolic blood pressure of 90-109 mmHg be
      included?
AB  - It is generally accepted that patients with a systolic blood pressure (SBP)<90
      mmHg are in "shock" and have a worse prognosis than patients with a higher SBP.
      Our objective was to determine if patients with a SBP of 90-109 mmHg have a worse
      outcome than patients with a higher SBP following trauma. Patients with gastric,
      small bowel, and/or diaphragm injuries were identified retrospectively through
      the trauma database from 1980-2003. All 2071 patients underwent emergent
      laparotomy at an urban, level one trauma center. The mortality rate of patients
      with a SBP of 90-109 mmHg in the ED or OR was 5% (17/354) and significantly
      higher than the 1% (12/1020) mortality seen in patients with a SBP of 110 mmHg or
      greater (P<0.001). The average length of stay of patients with a SBP of 90-109
      mmHg was 15+/-14 days and was significantly longer than the 11+/-11 days seen in
      patients with a higher SBP. If the SBP was 90-109 mmHg, the infection rate was
      39% (131/340), and this was significantly higher than the 22% (219/1016)
      infection rate seen in patients with higher SBP (P<0.001). Trauma patients with a
      systolic blood pressure of 109 mmHg or below are at increased risk for morbidity
      and mortality following trauma. Patients with a systolic blood pressure of 90-109
      mmHg following trauma should be considered as a special group requiring
      aggressive resuscitation and surgery. Early operative control of hemorrhage in
      these patients can reduce mortality and infection.

PMID- 17224787
TI  - Serum albumin levels anticipate antithrombin III activities before and after
      antithrombin III agent in critical patients with disseminated intravascular
      coagulation.
AB  - Elevated thrombin-antithrombin complex (TAT) or decreased serum albumin levels
      suggest heightened vascular permeability in disseminated intravascular
      coagulation (DIC). In such a situation, plasma antithrombin III (AT-III) may
      decrease because of the leakage. We thus examined whether AT-III activity before
      and after administration of an AT-III agent changed depending on plasma TAT
      and/or serum albumin levels in 20 consecutive patients with DIC. We also analyzed
      the pharmacokinetics for AT-III using a two-compartment model. Serum albumin
      levels before AT-III administration correlated with preadministered and
      postadministered AT-III activity, but TAT levels did not. Regardless of TAT
      levels, AT-III trough activity on the third day increased significantly. In
      patients with albumin levels of 2.5 g/dL or less, AT-III trough levels on the
      third day were significantly lower than those with higher levels of albumin. The
      half-life of the distribution phase for AT-III agent in the patients was
      shortened to less than one third the value reported in congenital AT-III
      deficiency, suggesting increased vascular permeability in the acute state
      patients here. The distribution volume of the agent increased remarkably compared
      with the previous control. We report here for the first time that in critical
      patients with DIC, plasma AT-III levels before and after AT-III administration
      could be predicted by preadministered serum albumin levels, but not by TAT. These
      findings could be explained by the pharmacokinetic profile, increased vascular
      permeability and distribution volume, observed in critical patients.

PMID- 17224788
TI  - Collagenase 2/matrix metalloproteinase 8 in critically ill patients with
      secondary peritonitis.
AB  - Secondary peritonitis is an important indication for surgical intensive care
      admissions, and it is associated with high morbidity and mortality. Collagenase
      2/matrix metalloproteinase (MMP) 8 is a tissue matrix-degrading enzyme that is
      released from leukocytes upon inflammatory stimuli and may thus contribute to
      peritonitis-associated organ damage. We studied the levels and activity of MMP-8
      in the peritoneal fluid of 15 critically ill patients with secondary peritonitis.
      The MMP-8 levels were measured from the patients' peritoneal fluid, serum, and
      urine, and from the serum and urine of 10 healthy controls by immunofluorometric
      assay. Median MMP-8 level in peritoneal fluid supernatant was 1,317 microg/L
      (interquartile range [IQR]) (1,254-1,359 microg/L) being significantly higher
      than in the sera of the patients (P=0.008). Molecular forms and isoform
      distribution of MMP-8, MMP-1, and MMP-13 in peritoneal fluid, assessed by Western
      immunoblotting, revealed that the neutrophil-type MMP-8 was the major collagenase
      species in peritoneal fluid, and it was partially in an activated form.
      Catalytically competent, active MMP-8 produced the characteristic cleavage
      products from intact human type I collagen. The serum levels of MMP-8 were higher
      in the patients, 49 microg/L (IQR, 23-214 microg/L), than in the controls, 11
      microg/L (IQR, 8-24 microg/L) (P<0.01). The MMP-8 levels in the urine were higher
      in the patients, 0.27 microg/L (IQR, 0.04-1.89 microg/L), than in the controls,
      0.03 microg/L (IQR, 0.0-0.05 microg/L) (P=0.013). Our data demonstrate for the
      first time that MMP-8 levels are remarkably elevated and in an active and
      catalytically competent form in the peritoneal fluid samples of patients with
      secondary peritonitis.

PMID- 17224789
TI  - Influence of sex and age on mods and cytokines after multiple injuries.
AB  - Although salutary effects of female sex steroids have been demonstrated not only
      in proestrus females but also in male animals treated with estradiol in different
      models of trauma, it remains unknown whether sex hormones influence post
      traumatic immune response in humans. We therefore investigated the effect of sex
      and age on organ dysfunction and clinical course in patients with multiple
      injuries. Polytraumatized patients (injury severity score>16) between 16 and 65
      years old admitted to the Hannover Medical School Level 1 trauma center between
      January 1997 and December 2001 were included. Marshall Score for multiple organ
      dysfunction syndrome (MODS) was calculated for at least 14 days. The length of
      stay in intensive care unit and the ventilator days were recorded in addition to
      the number of transfusions the patient received. A total of 106 males and 37
      females were included in the study. Patients with MODS had increased plasma
      levels of IL-6, IL-8, and IL-10. Furthermore, patients with organ dysfunction had
      more frequent sepsis and higher mortality rates. In addition, MODS was associated
      with extended length of stay in the intensive care unit and increased ventilator
      days. Females not older than 50 years with an injury severity score greater than
      25 suffered significantly less MODS and sepsis compared with age-matched males.
      Moreover, they had significantly lower plasma cytokines. Thus, in this
      prospective study, sex difference was confirmed in MODS and sepsis, with a
      benefit observed in females. Although the levels of sex steroids were not
      measured, it seems that the protective effects may be due to estrogen effects on
      plasma cytokines. This suggestion is based on the fact that such salutary effects
      were apparent predominantly in premenopausal females.

PMID- 17224790
TI  - Early growth response 1 mediates the systemic and hepatic inflammatory response
      initiated by hemorrhagic shock.
AB  - Hemorrhagic shock (HS) is a major cause of morbidity and mortality in trauma
      patients. The early growth response 1 (Egr-1) transcription factor is induced by
      a variety of cellular stresses, including hypoxia, and may function as a master
      switch to trigger the expression of numerous key inflammatory mediators. We
      hypothesized that HS would induce hepatic expression of Egr-1 and that Egr-1
      upregulates the inflammatory response after HS. The Egr-1 mice and wild-type (WT)
      controls (n>or=5 for all groups) were subjected to HS alone or HS followed by
      resuscitation (HS/R). Other mice were subjected to a sham procedure which
      included general anesthesia and vessel cannulation but no shock (sham). After the
      HS, HS/R, or sham procedures, mice were euthanized for determination of serum
      concentrations of interleukin (IL) 6, IL-10, and alanine aminotransferase.
      Northern blot analysis was performed to evaluate Egr-1 messenger RNA (mRNA)
      expression. Liver whole cell lysates were evaluated for Egr-1 protein expression
      by Western blot analysis. Hepatic expression of IL-6, granulocyte colony
      stimulating factor, and intracellular adhesion molecule 1 mRNA was determined by
      semiquantitative reverse transcriptase-polymerase chain reaction. The Egr-1 DNA
      binding was assessed using the electrophoretic mobility shift assay. Hemorrhagic
      shock results in a rapid and transient hepatic expression of Egr-1 mRNA in WT
      mice by 1 h, whereas protein and DNA binding activity was evident by 2.5 h. The
      Egr-1 mRNA expression diminished after 4 h of resuscitation, whereas Egr-1
      protein expression and DNA binding activity persisted through resuscitation. The
      Egr-1 mice exhibited decreased levels of hepatic inflammatory mediators compared
      with WT controls with a decrease in hepatic mRNA levels of IL-6 by 42%,
      granulocyte colony-stimulating factor by 39%, and intracellular adhesion molecule
      1 by 43%. Similarly, Egr-1 mice demonstrated a decreased systemic inflammatory
      response and hepatic injury after HS/R compared with their WT counterparts. Early
      growth response 1 is rapidly upregulated in the liver during and after
      resuscitation from HS. Our results showing a blunted inflammatory response in Egr
      1 mice provides evidence that Egr-1 functions as a proximal signal transduction
      mechanism responding to shock by amplifying the systemic inflammatory response.

PMID- 17224791
TI  - Carbon monoxide inhalation rescues mice from fulminant hepatitis through
      improving hepatic energy metabolism.
AB  - Heme oxygenase 1 (HO-1) enhances cellular antioxidative capability by increasing
      the cleavage of the endogenous and exogenous heme. Besides the biochemical
      activities of HO, the products of heme degradation significantly contribute to
      the cytoprotective effects of HO. Here, we show that HO-1 deficiency
      significantly increases the susceptibility of mice to apoptotic insults, whereas
      expression of HO-1 significantly increased the resistance of primary hepatocyte
      to apoptosis. This phenomenon was correlated with the production of one of its
      catalytic products-carbon monoxide (CO). Surprisingly, exposing the primary mouse
      hepatocyte to CO could improve the cellular energy metabolism in a soluble
      guanylyl cyclase-dependent manner. One-hour inhalation of low-dose CO enhanced
      the hepatic soluble guanylyl cyclase activities in mice. In parallel, the levels
      of hepatic adenosine triphosphate increased significantly and were associated
      with a marked reduction of TNF-alpha-induced apoptosis in the liver of D
      galactosamine-sensitized mice. In addition, CO inhalation for 1 h significantly
      improved the survival of mice after initiation of fulminant hepatitis. Up to 90%
      of mice given CO survived for more than 7 days, whereas control mice died within
      12 h. The data provide novel insight of CO-mediated cytoprotection.

PMID- 17224792
TI  - Hypertonic saline solution increases the expression of heat shock protein 70 and
      improves lung inflammation early after reperfusion in a rodent model of
      controlled hemorrhage.
AB  - Hypertonic saline solution (HS solution, NaCl 7.5%) has shown to restore
      hemodynamic parameters in hemorrhagic shock and to decrease the inflammation
      triggered by ischemia-reperfusion injury (I-R). Therefore, our objective was to
      investigate the effects of HS solution on the mechanisms involved in I-R, in an
      experimental model of controlled hemorrhagic shock. Wistar rats (280-350 g) were
      submitted to controlled bleeding, keeping the mean arterial pressure around 40
      mmHg, for 1 h. After that, rats were randomized and treated with HS solution (4
      mL/kg) or normal saline (34 mL/kg). There were no differences in hemodynamic
      parameters between both groups for at least 2 h after shock. No difference either
      was observed in reactive oxygen species generation (measured indirectly by
      malondialdehyde concentration) or cytokines (interleukins 6 and 10) production
      (measured by enzyme-linked immunosorbent assay). Quantitative analysis of lung
      tissue showed a smaller neutrophil infiltration in animals that received HS
      solution. Moreover, the animals in the HS group showed an increased expression of
      heat shock protein 70. Therefore, we concluded that treatment of hemorrhagic
      shock with HS solution can decrease pulmonary inflammation and increase cellular
      protection by up-regulating heat shock protein 70 expression.

PMID- 17224793
TI  - Heat shock stress ameliorates cytokine mixture-induced permeability by
      downregulating the nitric oxide and signal transducer and activator of
      transcription pathways in Caco-2 cells.
AB  - Proinflammatory cytokines are known to impair intestinal barrier function and to
      activate signaling pathways, whereas heat shock responses prevent cytokine
      induced mucosal damage. We hypothesized that heat shock response blocks the
      effects of proinflammatory cytokines by regulating nitric oxide (NO) production
      and the activities of the Janus kinase/signal transducer and activator of
      transcription (STAT) pathway. A monolayer of Caco-2 cells were pretreated with
      sodium arsenite (SA, 500 micromol/L) for 1 h, followed by a 1-h recovery, and
      then stimulated with a cytokine mixture (cytomix: tumor necrosis factor alpha [10
      ng/mL], interferon beta [1000 U/mL], and interleukin [IL] 1beta [1 ng/mL]) for 24
      h. The permeability of horseradish peroxidase and fluorescein isothiocyanate
      conjugated Dextran and transepithelial resistance and potential difference were
      measured in Ussing chambers. Interleukin-6, IL-8, NO, inducible NO synthase mRNA,
      STAT activity, and suppressor of cytokine signaling (SOCS) expression were
      measured in medium or cell lysates. Cytomix resulted in increased epithelial
      permeability of both fluorescein isothiocyanate-conjugated Dextran and
      horseradish peroxidase; whereas treatment of Caco-2 cells with SA 500 micromol/L
      blocked the cytomix-induced permeability changes. In addition, SA treatment
      decreased cytomix-induced NO production and inducible NO synthase mRNA expression
      and decreased the levels of STAT1, STAT3, SOCS1, and SOCS3. The SA treatment also
      decreased cytomix-induced IL-6 and IL-8 production in a dose-dependent manner. In
      conclusion, cytomix increased epithelial permeability, which is associated with
      increased NO and STAT activities. The SA treatment ameliorated cytomix-induced
      permeability, possibly through the downregulation of the NO and Janus kinase/STAT
      pathways.

PMID- 17224794
TI  - Lipopolysaccharide O-antigen promotes persistent murine bacteremia.
AB  - Bacteremia is a common complication of pneumonia with Klebsiella pneumoniae. In
      the previous work, we have shown that the lipopolysaccharide (LPS) O-antigen in
      K. pneumoniae O1:K2 contributes to lethality during pneumonia in part by
      promoting bacteremia. In the current work, we studied an O-antigen-deficient K.
      pneumoniae strain to further evaluate this polysaccharide's role in bloodstream
      infection. Cultured macrophage and murine bacteremia models were studied. In
      vitro, O-antigen-deficient bacteria, compared with wild-type organisms, were
      stronger activators of the murine alveolar macrophage cell line MH-S as assessed
      by nuclear localization of RelA/p65 and by secretion of cytokines and chemokines.
      O-antigen-deficient Klebsiellae were also more susceptible to killing by murine
      neutrophils. In vivo, the absence of O-antigen allowed more rapid and complete
      clearance of bacteria from the bloodstream, liver, and spleen after intravenous
      injection in mice. Survival was also greater among animals infected with bacteria
      missing the O-antigen. Gene expression profiling (via reverse transcriptase
      polymerase chain reaction of 84 inflammatory mediator complementary DNA) revealed
      that by 24 h postinfection, the livers and spleens of animals infected with O
      antigen-deficient organisms had significantly downregulated cytokine and
      chemokine expression compared with wild-type infected animals. The O-antigen
      surface carbohydrate of O1:K2 serotype K. pneumoniae appears to contribute to
      bacterial virulence by lessening the activation of macrophages, conveying
      resistance to killing by neutrophils, and by promoting persistent infection in
      the blood, liver, and spleen after the onset of bacteremia.

PMID- 17224795
TI  - Hypotensive hemorrhage increases calcium uptake capacity and Bcl-XL content of
      liver mitochondria.
AB  - We tested the hypothesis that the response of mitochondrial uptake of calcium and
      content of Bcl proteins to reversible hemorrhagic shock increases the
      vulnerability for hepatocellular death. Pentobarbital-anesthetized rats were bled
      to a mean arterial pressure of 30 to 40 mmHg for 1 h. A subset was then
      resuscitated (isotonic sodium chloride solution, three times shed volume). Liver
      mitochondria were isolated at the end of hemorrhage and 1.5 h after the onset of
      resuscitation. Resuscitation accelerated mitochondrial respiration in the
      presence of adenosine diphosphate (state 3) above control (P<0.01). The
      respiratory control ratio ([RCR] state 3/state 4) was calculated using the
      respiratory rate in the presence of carboxyatractyloside (state 4). The RCR was
      depressed at the end of hemorrhage and recovered completely in response to
      resuscitation (P<0.05). The mitochondrial capacity for calcium uptake increased
      at the end of hemorrhage and remained greater than control (P<0.01) after
      resuscitation when plasma ornithine carbamoyltransferase (an index of
      hepatocellular injury) was greater than control (P<0.05). At this time, the
      capacity for calcium uptake was correlated with plasma ornithine
      carbamoyltransferase (r=0.819, P<0.01). Mitochondrial content of Bcl-xL, an
      antiapoptotic protein, was increased at the end of hemorrhage (P<0.03) with no
      further change after resuscitation and no change in mitochondrial Bak, a
      proapoptotic protein. Thus, mitochondrial mechanisms are triggered early during
      reversible hypovolemia that may limit the intensity of intracellular calcium
      signaling and its potential to cause cellular injury and death.

PMID- 17224796
TI  - Sesame oil attenuates Cisplatin-induced hepatic and renal injuries by inhibiting
      nitric oxide-associated lipid peroxidation in mice.
AB  - Although cisplatin (cis-diamminedichloroplatinum) is an effective drug for the
      treatment of several solid tumors and has been used therapeutically for decades,
      several cisplatin-induced side effects have limited its therapeutic dosage in
      clinical studies. Our aim was to examine the effect of sesame oil on cisplatin
      induced hepatic and renal injuries in mice (8-week-old female SPF C57BL/6) given
      subcutaneous cisplatin (0, 5, 10, or 20 mg/kg). Hepatic and renal functions,
      lipid peroxidation (LPO) levels, and reactive oxygen free radicals were evaluated
      3 days after cisplatin administration, and tumor volumes were recorded 0, 3, 6,
      and 9 days after cisplatin administration. Sesame oil (i) potently attenuated
      cisplatin-associated hepatic and renal injuries; (ii) decreased cisplatin
      initiated LPO as well as the production of hydroxyl radical, peroxynitrite, and
      nitrite in blood and tissue; and (iii) did not affect the antitumor capacity
      exerted by cisplatin in mice with melanoma. We suggest that sesame oil attenuates
      cisplatin-induced hepatic and renal damage by at least partially inhibiting
      nitric oxide-associated LPO in mice. Sesame oil might be a new approach for
      preventing cisplatin-induced multiple organ injury during the treatment of
      tumors.

PMID- 17224797
TI  - Insulin attenuates the cytokine response in a burn wound infection model.
AB  - A massive burn is one of the most serious injuries resulting in major imbalances
      of the immune system. The aftermath of a burn is frequently complicated by
      infections and septic events that additionally increase mortality and morbidity.
      The aim of the present study was to investigate if insulin attenuates the
      cytokine response of burned mice challenged with Pseudomonas. Male mice
      (C57/BL/6) received a full thickness burn of 35% of their total body surface
      area. Mice received 5 IU/kg insulin i.p. or an equal volume of saline for 5 days
      after burn. Mice were challenged with 5x10 colony forming units Pseudomonas
      aeruginosa intraperitoneally. Serum was harvested 6 h after the bacterial
      challenge, and 18 serum cytokines were measured using the Bio-Plex suspension
      array system (Bio-Rad, Hercules, Calif). All 18 cytokines were elevated after the
      Pseudomonas challenge. However, mice treated with insulin showed significantly
      lower proinflammatory cytokine concentrations of interleukin 5, interleukin 6,
      and keratinocyte-derived chemokine after the Pseudomonas infection when compared
      with placebo-treated mice (P<0.05). In contrast, serum concentrations of G-CSF
      were significantly higher in insulin-treated animals when compared with placebo
      (P<0.05). We conclude, that insulin treatment selectively modulates specific
      cytokines in a burn wound infection model.

PMID- 17224798
TI  - Lymphatic thoracic duct ligation modulates the serum levels of IL-1beta and IL-10
      after intestinal ischemia/reperfusion in rats with the involvement of tumor
      necrosis factor alpha and nitric oxide.
AB  - Intestinal ischemia/reperfusion (I/R) causes local and remote injuries that are
      multifactorial and essentially inflammatory in nature. To study the putative
      influences of nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) on
      the release of interleukin (IL) 1beta and IL-10 and the involvement of lymphatic
      system on a systemic inflammation caused by I/R, we have quantified the serum and
      lymph levels of IL-1beta and IL-10 in rats during I/R after treatment with
      inhibitors of NO synthase (N-nitro-L-arginine methyl ester hydrochloride [L
      NAME]) or TNF-alpha (pentoxifylline [PTX]). Intestinal I/R was performed by means
      of a 45-min occlusion of the mesenteric artery, followed by 2-h reperfusion;
      groups of rats subjected to I/R had the thoracic lymph duct ligated immediately
      before the procedure. The I/R caused a significant increase of the serum levels
      of IL-1beta and IL-10 in rats with intact thoracic lymph duct, whereas the
      thoracic duct ligation blunted the serum release of IL-1beta and elevated that of
      IL-10. The levels of the cytokines collected in the lymph after I/R increased,
      and even more increase was observed in L-NAME-treated rats. L-NAME significantly
      increased the lymph levels of IL-1beta and IL-10; in serum, however, only IL
      1beta increased in rats with either intact or ligated thoracic lymph duct. The
      treatment with PTX reduced the serum levels of IL-1beta irrespective of the lymph
      circulation interruption but was effective to increase the IL-10 levels in intact
      rats during I/R. The lymphatic levels of IL-1beta of rats subjected to I/R were
      reduced and those of IL-10 were increased after treatment with PTX. In
      conclusion, during I/R, the serum levels of IL-1beta seem modulated by stimulant
      mechanisms that could be associated with TNF-alpha and inhibited by NO and by the
      integrity of the thoracic lymphatic flow. On the other hand, IL-10 seems
      controlled by TNF-alpha-related, largely NO-independent mechanisms. Thus, it is
      reasonable to suppose that an endogenous mechanism that can limit the systemic
      inflammatory response ensuing an I/R splanchnic trauma exists.

PMID- 17224799
TI  - Adenosine deaminase acting on RNA 1 accelerates cell cycle through increased
      translation and activity of cyclin-dependent kinase 2.
AB  - Adenosine-to-inosine RNA editing has been recently implicated in the pathogenesis
      of inflammation through the upregulation of the editase adenosine deaminase
      acting on RNA 1 (ADAR1). Because cell proliferation is a key feature of the
      inflammatory process, the present study tested the hypothesis that overexpression
      of ADAR1 accelerates cell cycle. To that end, human embryonic kidney 293 cells
      were transiently transfected with ADAR1 or vector, and cell cycle was evaluated
      by fluorescence-activated cell sorter. Overexpression of wild-type ADAR1
      decreased the proportion of G0-G1 cells (-19%, P<0.01, n=3), increased the
      percentage of S phase cells (+19%, P<0.01, n=3), and did not change the ratio of
      cells residing in the G2-M phase (n=3). This finding was supported by three
      observations. First, there was a parallel production in ADAR1-transfected cells
      of cyclin-dependent kinase (Cdk) 2 and cyclin A, a pivotal protein complex
      upregulated at the G1-S phase checkpoint, and of [p]-Histone H1, a marker of Cdk2
      activity (+102%, P<0.01, n=3). Second, ADAR1-transfected cells displayed higher
      activity of the proliferation marker, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      2H-tetrazolium bromide. Third, using anti-ADAR1 antibody, direct binding of ADAR1
      to Cdk2 messenger RNA was demonstrated in ADAR1-transfected cells by protein-RNA
      cross-linking and immunoprecipitation (+974%, P<0.01, n=3). Finally, causal
      relationships between ADAR1 and Cdk2 were confirmed by a study with the Cdk2
      inhibitor, kenpaullone, which prevented the ADAR1-induced shift from the G0-G1 to
      the S phase. Taken together, these data show that ADAR1 increases cell cycle by
      shifting cells from the G0-G1 to the S phase through the upregulation of Cdk2.

PMID- 17224800
TI  - Randomized clinical study to compare the accuracy of navigated and non-navigated
      thoracic pedicle screws in deformity correction surgeries.
AB  - STUDY DESIGN: Randomized clinical trial (level I evidence). OBJECTIVE: To compare
      the accuracy of non-navigation and Iso-C based navigation in pedicle screw
      fixation in thoracic spine deformities. SUMMARY OF BACKGROUND DATA: Thoracic
      pedicle screw insertion for spinal deformity correction can be associated with
      increased pedicle breaches. Iso-C based navigation has been reported to improve
      the accuracy of pedicle screw placement, but its use in the presence of deformity
      has not been reported. METHODS: Twenty-seven patients with scoliosis and 6
      patients with kyphosis had a total of 478 thoracic pedicle screws. The average
      Cobb angle was 58.4 degrees +/- 8 degrees (range 50 degrees -80 degrees), and the
      mean kyphotic angle was 54.6 degrees +/- 4 degrees (range 51 degrees -76
      degrees). By random allocation, 17 patients had screw insertion under navigation
      (242 screws) and 16 under fluoroscopic control (236 screws). The 2 groups were
      compared for accuracy of screw placement, time for screw insertion, and the
      number of times the C-arm had to be brought into the field. Two independent
      blinded observers determined accuracy using postoperative computed tomography
      assessments. RESULTS: There were 54 (23%) pedicle breaches in the non-navigation
      group as compared to only 5 (2%) in the navigation group (P < 0.001). Thirty
      eight screws (16%) in the non-navigation group had penetrated the anterior or
      lateral cortex compared to 2 screws (0.8%) in the navigation group. Average screw
      insertion time in the non-navigation group was 4.61 +/- 1.05 minutes (range 1.8
      6.5) compared to 2.37 +/- 0.72 minutes (range 1.16-4.5) in navigation group (P <
      0.01). The C-arm had to be moved into the operation field on an average of 1.5 +/
      0.25 times (range 1-3) per screw. With single screening data, an average of 11.4
      pedicles (range 9-14) could be visualized without necessity to bring the C-arm
      into operating field again. CONCLUSIONS: Iso-C navigation increases accuracy, and
      reduces surgical time and radiation in thoracic deformity correction surgeries.

PMID- 17224801
TI  - Electrophysiologic changes in dorsal root ganglion neurons and behavioral changes
      in a lumbar radiculopathy model.
AB  - STUDY DESIGN: The DRG neuron was electrophysiologically investigated using a rat
      model with constriction of the proximal site of the DRG. OBJECTIVES: To
      investigate the pathomechanisms of lumbar radiculopathy, we established a rat
      model with constriction of the proximal site of the DRG. And to characterize the
      DRG neurons in the rat model of lumbar radiculopathy, the physiologic properties
      regarding action potential, Na, and K current of the DRG neurons were analyzed
      through the use of patch clamp recordings. SUMMARY OF BACKGROUND DATA: In lumbar
      root constriction models, properties of secondary afferent neurons in the dorsal
      horn have been investigated. However, the electrical properties of DRG neuron
      have not been well investigated. METHODS: To compare the excitability of DRG
      neurons between root constriction models and sham, we examined the threshold
      current, action potential (AP) threshold, resting membrane potential (RMP),
      afterhyperpolarization (AHP), action potential duration 50 (APD50), action
      potential amplitude, maximum rise time of AP, and pattern of discharges evoked by
      depolarizing current. We also examined the peak Na current and steady-state Na
      and K currents with the voltage clamp technique. RESULTS: The rats in the root
      constriction group demonstrated mechanical allodynia and thermal hyperalgesia. In
      measurement of the action potential, lower threshold current, more depolarized
      RMP, larger AHP, and prolonged APD50 were measured in the root constriction
      neurons compared with the sham group. The incidence of sustained burst was
      significantly higher in root constriction neurons. The Na current in root
      constriction neurons was markedly larger. There were no significant differences
      in K current density and voltage dependency. CONCLUSIONS: The constriction of
      lumbar root increased excitability and Na current amplitude of DRG neurons. These
      findings indicate that lumbar radicular pain may be associated with increased
      excitability of involved DRG neurons.

PMID- 17224802
TI  - Effects of the mechanical load on forward bending motion of the trunk: comparison
      between patients with motion-induced intermittent low back pain and healthy
      subjects.
AB  - STUDY DESIGN: Postural changes and trunk muscle activities were examined in
      patients with motion-induced intermittent low back pain (MILBP) and healthy
      controls. OBJECTIVES: To assess the ability to maintain an upright standing
      position. SUMMARY OF BACKGROUND DATA: Since MILBP is not observed at rest, its
      pathophysiology is complicated to investigate. METHODS.: Postural changes were
      measured with a 3-dimensional motion analyzer, and muscle activities with a
      surface electromyography while 10 female patients at an average age of 76 years
      (MILBP group) and 10 healthy controls at an average age of 74 years (Control
      Group) were standing upright and loaded with 10-kg weights. RESULTS: In the
      Control Group, no significant forward bending motion occurred. In the MILBP
      group, there was a temporal increase in forward bending at various speeds and at
      various time phases. In the MILBP group but not in the Control Group, the rate of
      changes in median power frequency of erector spinae muscle declined significantly
      as compared with that in the Control Group (P < 0.05). CONCLUSIONS: These results
      indicated that fatigue of the back muscles occurred in MILBP patients and could
      be a pain generator in low back pain.

PMID- 17224803
TI  - Plasma neuropeptides in patients undergoing lumbar discectomy.
AB  - STUDY DESIGN: A prospective analysis of patients with lumbar disc herniation
      (LDH). OBJECTIVES: To determine the role of neuropeptides as a biochemical
      signature of pain states in patients with LDH. SUMMARY OF BACKGROUND DATA:
      Increases in the plasma level of neuropeptides have been reported in patients
      suffering from a variety of painful conditions. However, there is no such report
      on patients with LDH. METHODS: From a total of 27 patients with a single-level
      LDH, blood samples were collected before and 3 weeks after lumbar discectomy.
      Plasma levels of alpha calcitonin gene-related peptide (CGRP), galanin,
      neuropeptide Y, and substance P were determined by using enzyme-linked
      immunosorbent assay. The association or correlation between preoperative
      concentration of plasma neuropeptides and gender, patients' age, and VAS were
      analyzed statistically. Also, the concentration of plasma neuropeptides was
      compared before and after lumbar discectomy. RESULTS: Preoperative plasma levels
      of CGRP were correlated significantly with the extent of sciatica as determined
      by VAS. In addition, plasma levels of CGRP and galanin significantly decreased
      after lumbar discectomy in line with the disappearance of pain symptoms.
      CONCLUSIONS: These findings indicate the role of plasma CGRP and possibly galanin
      as a systemic neurochemical signature of pain states in patients with LDH.

PMID- 17224804
TI  - Radiographic assessment of lumbar facet distance spacing and spondylolysis.
AB  - STUDY DESIGN: Spondylolytic defects at L5 are influenced by insufficient
      differential spacing between the inferior articular facets of L4 and superior
      facets of S1. These structures then impinge on the intervening L5 pars
      interarticularis during hyperlordosis, contributing to fracture and resorption of
      the pars. OBJECTIVES: Articular facet spacing was evaluated on clinical
      radiographs of normal and spondylolytic patients. SUMMARY OF BACKGROUND DATA:
      Spondylolysis ranges from a hairline fracture through the pars to a complete
      pseudarthrotic defect. Insufficient increase in the distance between articular
      facets from L4-L5 to L5-S1 has been associated with chronic lytic defects in a
      skeletal sample. METHODS: Anteroposterior radiographs of 39 patients with L5-S1
      spondylolysis were compared with radiographs from 42 normal individuals.
      Differences in transverse distances between lumbar articular facets and pedicles
      were compared using 2-tailed t tests. RESULTS: Patients with spondylolysis
      exhibited a smaller increase in interfacet distance from the L3-L4 facet joints
      to the L5-S1 joints than do normal patients, even relative to vertebral size.
      CONCLUSIONS: Spondylolytic fractures at L5 are influenced by an inadequate
      increase in interfacet distances between adjacent vertebrae. Individuals lacking
      sufficient increase in lower lumbar transverse interfacet dimensions are at
      greater risk of developing and maintaining spondylolytic defects.

PMID- 17224805
TI  - Classification of chance fracture in children using magnetic resonance imaging.
AB  - STUDY DESIGN: MRI study of pediatric Chance fracture. OBJECTIVE: To evaluate bone
      and soft tissue lesions in pediatric Chance fracture. SUMMARY OF BACKGROUND DATA:
      Several descriptions and classifications have been already developed for Chance
      fracture, but mainly for adult. Furthermore, they are all based only on
      radiographic studies. METHODS: MRI and radiographs of 18 children with Chance
      fracture were analyzed before treatment. RESULTS: On MRI, in all cases, no
      abnormal signs were noted on the intervertebral disc. Six patients had a bone
      fracture going through the pedicle and the vertebral body. Twelve patients had a
      physeal injury located on the superior or on the inferior vertebral endplate.
      Three types of lesions could be identified according to the location of the
      lesion in relation to the pedicle. CONCLUSION: MRI is useful in the diagnosis of
      pediatric Chance fracture. It allows physeal injury to be clearly identified from
      disc injury.

PMID- 17224806
TI  - Percutaneous endoscopic discectomy for extraforaminal lumbar disc herniations:
      extraforaminal targeted fragmentectomy technique using working channel endoscope.
AB  - STUDY DESIGN: A retrospective analysis of 41 patients operated for excision of
      soft lumbar extraforaminal disc herniation (EFDH) by percutaneous endoscopic
      extraforaminal approach under local anesthesia by a new technique. OBJECTIVES: To
      describe a new and safer percutaneous endoscopic technique for the removal of
      soft EFDH and report the results on the basis of a new objective criterion
      modified from Oswestry Disability Index (ODI). SUMMARY OF BACKGROUND DATA: EFDHs
      usually occur in older patients and present with atypical symptoms. Their
      diagnosis and treatment are still controversial, with various authors describing
      open midline or paraspinal approaches using the microscope with varying amounts
      of success. Percutaneous endoscopic techniques have traditionally been considered
      unsuitable for these herniations. METHODS: Forty-one patients with a soft EFDH
      were subjected to percutaneous endoscopic discectomy with the new technique. In
      our technique, the skin entry point is medial and the angle of approach steeper
      as compared with the earlier described endoscopic techniques. This might help in
      avoiding exiting root injury and increasing the efficacy of the procedure. The
      results were analyzed on the basis of percentage change in ODI as compared with
      preoperative values. RESULTS: Mean follow-up was 34.1 month. Mean VAS score for
      radicular pain improved from 8.6 to 1.9, and mean ODI improved from 66.3 to 11.5.
      Overall, 92% of patients experienced satisfactory outcome. Two patients had poor
      outcome due to the need for subsequent open surgery. CONCLUSION: Percutaneous
      endoscopic discectomy using the "extraforaminal targeted fragmentectomy"
      technique is an effective and safe procedure for the select group of patients
      with a soft EFDH.

PMID- 17224808
TI  - Addition of choice of complementary therapies to usual care for acute low back
      pain: a randomized controlled trial.
AB  - STUDY DESIGN: A randomized controlled trial. OBJECTIVE: To investigate the
      effectiveness and cost of usual care plus patient choice of acupuncture,
      chiropractic, or massage therapy (choice) compared with usual care alone in
      patients with acute low back pain (LBP). SUMMARY OF BACKGROUND DATA: Few studies
      have evaluated care models with facilitated access to and financial coverage for
      adjunctive complementary and alternative medicine therapies. METHODS: A total of
      444 patients with acute LBP (<21 days) were recruited from 4 clinical sites and
      randomized into 2 groups: usual care or choice. Outcomes included symptoms
      (bothersomeness), functional status (Roland), and satisfaction between baseline
      and 5 weeks, and cost of medical care in the 12 weeks after randomization.
      RESULTS: After 5 weeks, providing patients with a choice did not yield clinically
      important reductions in symptoms (median -4, [interquartile range -7, -2] for
      usual care, and -5 [-7, -3] for choice; P = 0.002) or improvements in functional
      status (-8 [-13, -2] for usual care, and -9 [-15, -4] for choice; P = 0.15).
      Although there was a significantly greater satisfaction with care in the choice
      group, this came at a net increase in costs of 244 dollars per patient. This
      consisted of a 99 dollars reduction in the average cost to the insurer for
      medical care but an additional cost of 343 dollars, for an average of 6.0
      complementary and alternative medicine treatments per patient. CONCLUSIONS: A
      model of care that offered access to a choice of complementary and alternative
      medicine therapies for acute LBP did not result in clinically significant
      improvements in symptom relief or functional restoration. This model was
      associated with greater patient satisfaction but increased total costs. Future
      evaluations of this choice model should focus on patients with chronic conditions
      (including chronic back pain) for which conventional medical care is often costly
      and of limited benefit.

PMID- 17224809
TI  - Glial phosphorylated p38 MAP kinase mediates pain in a rat model of lumbar disc
      herniation and induces motor dysfunction in a rat model of lumbar spinal canal
      stenosis.
AB  - STUDY DESIGN: Immunohistochemical and behavioral study using rat models of lumbar
      disc herniation and cauda equina syndrome. OBJECTIVE: To investigate the
      expression of activated p38 mitogen-activated protein kinases (p38 MAP kinase;
      p38) in the spinal cord and to determine the effect of intrathecal administration
      of a specific p38 inhibitor on pain in a lumbar disc herniation model and on
      motor function and hypoalgesia in a spinal canal stenosis (SCS) model. SUMMARY OF
      BACKGROUND DATA: In pathologic lumbar disc herniation-induced neuropathic pain
      and compression of cauda equina-induced motor dysfunction and hypoalgesia caused
      by SCS, glia are activated and produce certain cytokines, including tumor
      necrosis factor-alpha (TNF-alpha) and interleukins, which play a crucial role in
      the pathogenesis of nerve degeneration. p38 is phosphorylated by these cytokines,
      suggesting that it may play an important role in pain transmission and nerve
      degeneration. Here we have examined the role of p38 in rat models of lumbar disc
      herniation and SCS. METHODS: Six-week-old male Sprague-Dawley rats were used. For
      the disc herniation model, autologous nucleus pulposus was applied to L5 nerve
      roots, which were then crushed. For the SCS model, a piece of silicon was placed
      under the lamina of the fourth lumbar vertebra. We assessed mechanical allodynia,
      hypoalgesia, and motor function using von Frey hairs, treadmill tests, and
      immunohistochemical localization of phosphorylated p38 (P-p38) in the cauda
      equina, dorsal root ganglion (DRG), and spinal cord, which were also double
      stained with NeuN (neuronal marker), GFAP (astrocyte/Schwann cell marker), or
      isolectin B4 (IB4; microglia marker). We also examined the effects of intrathecal
      administration of a specific p38 inhibitor, FR167653, on nucleus pulposus-induced
      pain, hypoalgesia, and motor dysfunction following SCS. RESULTS: We demonstrated
      that activated P-p38-immunoreactive cells in the spinal cord and cauda equina
      were not observed before nerve injury but appeared in the cauda equina, DRG, and
      spinal dorsal horn in the disc herniation and SCS models. Double-labeling
      revealed that most P-p38-immunoreactive cells were isolectin B4-labeled microglia
      and GFAP-immunoreactive Schwann cells. Intrathecal administration of the p38
      inhibitor FR167653 decreased mechanical allodynia in the disc herniation model
      and improved hypoalgesia and intermittent motor dysfunction in the SCS model.
      CONCLUSIONS: Our findings suggest that activated p38 may play an important role
      in the involvement of microglia in the pathophysiology of pain following lumbar
      disc herniation and mechanical hypoalgesia, and motor nerve dysfunction of cauda
      equina following SCS.

PMID- 17224810
TI  - Autoimmune properties of nucleus pulposus: an experimental study in pigs.
AB  - STUDY DESIGN: Assessment of activated T and B cells in a subcutaneous chamber
      filled with autologous nucleus pulposus using flow cytometry and
      immunohistochemistry. OBJECTIVES: To examine if subcutaneously placed autologous
      nucleus pulposus may attract activated T and B cells in an animal model. SUMMARY
      OF BACKGROUND DATA: Nucleus pulposus has been suggested to trigger an autoimmune
      response if exposed to the immune system, for example, in association with disc
      herniation. T-cell activation represents a hallmark in the generation of an
      autoimmune response, subsequently leading to the differentiation of B cells, but
      a causal association between the exposure of nucleus pulposus to the systemic
      circulation and T and B cell activation is still lacking. METHODS: Autologous
      nucleus pulposus was harvested from the intervertebral disc of 9 pigs and placed
      subcutaneously in perforated titanium chambers. In order to control for the
      effect of the titanium chamber, an additional empty chamber was placed
      subcutaneously in each pig. After 7 days, the pigs were killed and the chambers
      were harvested. Flow cytometry and immunohistochemistry were used for analysis of
      T-helper cells (CD4+), cytotoxic T cells (CD8+), and B cells (Igkappa) in the
      chamber exudates and T cells (CD45RC) in the remaining blood clot tissue of the
      chamber. RESULTS: As compared with the empty chambers, the proportion of
      activated T cells (CD4+ and CD8+) was significantly higher in the exudate of the
      nucleus pulposus filled chamber. The proportion of activated B cells expressing
      immunoglobulin kappa (Igkappa) was also significantly elevated in the exudate of
      the nucleus pulposus chambers. The analysis of the remaining chamber tissue
      revealed a significantly higher amount of T cells (CD45RC) in the nucleus
      pulposus chambers than in the empty chambers. CONCLUSIONS: The present findings
      indicate that nucleus pulposus attracts activated T and B cells. However, since
      the cell population in the nucleus pulposus of young pigs may differ from that of
      adult humans, the obtained data may not be directly transferred to the human
      situation of a disc herniation. The observations in the present study may
      nevertheless explain some of the local tissue reactions occurring in association
      with disc herniation and nerve root involvement, thereby providing further
      insight into the pathophysiology of sciatica.

PMID- 17224811
TI  - Effects of direct current electrical stimulation on gene expression of
      osteopromotive factors in a posterolateral spinal fusion model.
AB  - STUDY DESIGN: An in vivo model was used to determine levels of mRNA expression in
      response to direct current (DC) electrical stimulation in a rabbit posterolateral
      fusion model. OBJECTIVES: This study tested the possibility that DC stimulation
      at the surgery site would increase expression of genes related to bone formation
      relative to expression in autograft alone. SUMMARY OF BACKGROUND DATA: DC
      electrical stimulation as an adjunct treatment in spinal surgery has shown
      increased fusion rates when compared with autograft alone, yet the biology of
      such treatment is not fully understood. METHODS: Thirty New Zealand White rabbits
      were entered into the study. A posterolateral, intertransverse process fusion was
      performed bilaterally at L4-L5, with autogenous bone graft. An implantable DC
      stimulator was placed across the decorticated transverse processes before
      placement of autograft. Animals were killed at 3, 7, 14, 21, and 28 days. mRNA
      levels of BMP-2, 4, 6, 7, VEGF, FGF-2, TGF-beta, ALK-2, and ALK-3 were evaluated
      with real-time RT-PCR. RESULTS: mRNA expression was significantly higher in the
      DC stimulated animals versus the control animals for several of the genes
      studied. In particular, levels of mRNA were elevated for BMP-2, BMP-6, and BMP-7.
      CONCLUSIONS: This study shows for the first time that DC stimulation results in a
      sustained increase of multiple osteogenic genes, suggesting that the biologic
      mechanism for the DC-induced increase in the rate and extent of bone formation
      observed clinically may be mediated by the up-regulation of these osteoinductive
      factors.

PMID- 17224812
TI  - Hangman's fracture: a biomechanical comparison of stabilization techniques.
AB  - STUDY DESIGN: In vitro biomechanical flexibility experiment studying 5 sequential
      conditions. OBJECTIVE: To determine the biomechanical differences among 3
      fixation techniques after a simulated hangman's fracture. SUMMARY OF BACKGROUND
      DATA: Type II hangman's fractures are often treated surgically with a C2-C3
      anterior cervical discectomy, fusion, and plating. Other techniques include
      direct fixation with C2 pars interarticularis screws or posterior C2-C3 fixation
      connecting C2 pars screws to C3 lateral mass screws. METHODS: Seven cadaveric
      specimens (Oc-C4) were tested intact, after a simulated hangman's fracture, and
      after each fixation technique. Flexion, extension, lateral bending, and axial
      rotation were induced using nonconstraining torques while recording angular
      motions stereophotogrammetrically. RESULTS: Direct screw fixation reduced motion
      an average of 61% +/- 13% during lateral bending and axial rotation compared to
      the injured state (P < 0.007). However, instability remained during flexion and
      extension. Posterior C2-C3 rod fixation provided significantly greater rigidity
      than anterior plate fixation during lateral bending (P < 0.008) and axial
      rotation (P < 0.04). CONCLUSIONS: Direct fixation of the pars ineffectively
      limits flexion and extension after a Type II hangman's fracture. If pars screw
      fixation can be achieved, posterior C2-C3 fixation more effectively stabilizes a
      hangman's fracture than anterior cervical plating.

PMID- 17224813
TI  - Histomorphometric assessment of thoracoscopically assisted anterior release in a
      porcine model: safety and completeness of disc discectomy with surgeon learning
      curve.
AB  - STUDY DESIGN: A retrospective study using histomorphometric analysis to quantify
      the percentage of discectomy following thoracoscopic anterior release and fusion
      in a porcine model. OBJECTIVE: To investigate the safety and completeness of disc
      and endplate removal with respect to the learning curve of the surgeon in a
      porcine thoracoscopic anterior fusion model. SUMMARY OF BACKGROUND DATA: The
      thoracoscopic approach has been used to perform an anterior release and fusion
      before an open posterior instrumentation, however, there is concern that the
      technique may not provide sufficient visualization or exposure to perform safely
      and completely. METHODS: A total of 32 pigs (160 discs) were assigned to 2 groups
      (early experience, n = 16; late experience, n = 16), and underwent 5 level
      thoracoscopic anterior release followed by anterior instrumentation and fusion
      from T5 to T10. At 4 months after surgery, the spines were harvested, and each
      discectomy disc was histomorphometrically analyzed to determine the percentage of
      disc excision and amount of endplate removal. RESULTS: There were no significant
      differences in the percent disc excision between the early (67% +/- 11%) and late
      groups (69% +/- 10%). Greater than 50% of the disc was excised in 151 of 160
      discectomies (94%). Both superior and inferior endplates were resected in 92 of
      160 disc levels (57%). The amount of endplate removal had improved over time in
      both early and late groups (P < 0.0001). The histologic examination revealed no
      evidence for posterior longitudinal ligament disruption or spinal canal
      encroachment in any disc. CONCLUSIONS: Video-assisted thoracoscopic discectomy is
      safe and allows for a significant amount of disc material excision. This study
      did not demonstrate a learning curve with respect to the amount of disc material
      excised, but a learning curve was seen for endplate excision.

PMID- 17224814
TI  - Radiosurgery for spinal metastases: clinical experience in 500 cases from a
      single institution.
AB  - STUDY DESIGN: A prospective nonrandomized, longitudinal cohort study. OBJECTIVE:
      To evaluate the clinical outcomes of single-fraction radiosurgery as part of the
      management of metastatic spine tumors. SUMMARY OF BACKGROUND DATA: The role of
      stereotactic radiosurgery for the treatment of spinal lesions has previously been
      limited by the availability of effective target immobilization and target
      tracking devices. Large clinical experience with spinal radiosurgery to properly
      assess clinical experience has previously been limited. METHODS: A cohort of 500
      cases of spinal metastases underwent radiosurgery. Ages ranged from 18 to 85
      years (mean 56). Lesion location included 73 cervical, 212 thoracic, 112 lumbar,
      and 103 sacral. RESULTS: The maximum intratumoral dose ranged from 12.5 to 25 Gy
      (mean 20). Tumor volume ranged from 0.20 to 264 mL (mean 46). Long-term pain
      improvement occurred in 290 of 336 cases (86%). Long-term tumor control was
      demonstrated in 90% of lesions treated with radiosurgery as a primary treatment
      modality and in 88% of lesions treated for radiographic tumor progression. Twenty
      seven of 32 cases (84%) with a progressive neurologic deficit before treatment
      experienced at least some clinical improvement. CONCLUSIONS: The results indicate
      the potential of radiosurgery in the treatment of patients with spinal
      metastases, especially those with solitary sites of spine involvement, to improve
      long-term palliation.

PMID- 17224815
TI  - Clinical outcome of posterolateral endoscopic surgery for pyogenic
      spondylodiscitis: results of 15 patients with serious comorbid conditions.
AB  - STUDY DESIGN: Clinical results of posterolateral endoscopic debridement and
      irrigation followed by percutaneous drainage for pyogenic spondylodiscitis were
      analyzed. OBJECTIVES: To report clinical results of transforaminal endoscopic
      surgery for pyogenic spondylodiscitis and to evaluate the effectiveness of this
      procedure in treatment of pyogenic spinal infections. SUMMARY OF BACKGROUND DATA:
      Pyogenic spinal infections have been increasing due to the development of medical
      treatment for patients with comorbid medical problems. Common treatments for
      spinal infections are administration of antibiotics or surgical debridement with
      bone grafts. There have been no reports, however, regarding the clinical outcome
      of posterolateral endoscopic treatment for pyogenic spinal infections. METHODS:
      Fifteen consecutive patients with pyogenic spondylodiscitis in the thoracic or
      lumbar spine were enrolled. Preoperative antibiotic treatment had failed in all
      the patients. The procedures consisted of posterolateral endoscopic debridement
      and irrigation followed by percutaneous drainage through single portal under the
      combination of local and intravenous anesthesia. Pain response using visual
      analog scale (VAS, 0-100 mm), inflammation parameters, and duration of antibiotic
      therapy were investigated. Radiologic evaluation focused on bony fusion, local
      kyphosis, disc height reduction, and abscess formation. RESULTS: All patients
      showed immediate pain reduction after surgery. Averaged VAS for pain was 86
      before surgery and 25 at postoperative 1 week. Average of CRP was 4.00 mg/dL
      before surgery and 1.88 mg/dL at postoperative 1 week. Averaged duration of
      antibiotics therapy was 3.7 weeks. Spinal fusion was obtained in 13 patients. Two
      patients with neurologic deficits due to epidural abscess returned to normal.
      Preoperative psoas abscess in 6 patients disappeared after surgery on MRI.
      CONCLUSIONS: Posterolateral spinal endoscopic debridement and irrigation brought
      immediate pain reduction and good clinical results to patients who had comorbid
      medical problems and had pyogenic spondylodiscitis.

PMID- 17224816
TI  - Cauda equina syndrome: factors affecting long-term functional and sphincteric
      outcome.
AB  - STUDY DESIGN: Retrospective cohort study with prospective clinical follow-up.
      OBJECTIVE: To determine the factors that influence outcome after surgery for
      cauda equina syndrome (CES). SUMMARY OF BACKGROUND DATA: CES is a rare but
      serious consequence of lumbar disc prolapse and can have devastating long-lasting
      neurologic consequences. The timing of surgical decompression remains
      controversial. METHODS: Fifty-six patients with evidence of a sphincteric
      disturbance who underwent urgent surgery were identified and invited to follow
      up. The outcome measures comprised history and examination and several validated
      self-assessment questionnaires. RESULTS: Forty-two patients (78%) attended with a
      mean follow-up of 60 months (range, 25-114 months). Mean age at onset was 41
      years (range, 24-67 years) with 23 males and 19 females. Twenty-six patients were
      operated on within 48 hours of onset of sphincteric symptoms; 5 of these were
      within 24 hours. Acute onset of sphincteric symptoms and the time to operation
      did not influence the outcomes. Leg weakness at onset persisted in a significant
      number of patients at follow-up (P < 0.005). Urinary disturbance at presentation
      did not affect the outcomes. At follow-up, significantly more females had urinary
      incontinence (P < 0.005). Bowel dysfunction at presentation was associated with
      sexual problems at follow-up (P < 0.005). The 13 patients who failed their post
      operative trial without catheter had worse outcomes. The SF-36 scores at follow
      up were reduced compared with age-matched controls in the population. The mean
      ODI was 29, Low Back Outcome Score 42, and VAS 4.5. The time elapsed from
      operation to follow-up was not found to influence the outcomes. CONCLUSIONS: In
      our series, the symptom duration before operation and the speed of onset do not
      affect the outcome more than 2 years after surgery. Based on the SF-36, ODI, and
      Low Back Outcome Scores, patients who have had CES do not return to a normal
      status.

PMID- 17224817
TI  - Fluoroscopic computer-assisted pedicle screw placement through a mature fusion
      mass: an assessment of 24 consecutive cases with independent analysis of computed
      tomography and clinical data.
AB  - STUDY DESIGN: Observational matched cohort study with computed tomography (CT)
      analysis of pedicle screw placement. OBJECTIVE: Assess the clinical accuracy of
      computer-assisted fluoroscopy for the placement of thoracolumbar pedicle screws
      through a mature posterolateral fusion mass. SUMMARY OF BACKGROUND DATA: Pedicle
      screw placement through an amorphous posterolateral fusion mass intuitively
      carries a higher risk of pedicle wall violation. METHODS: Postoperative CT scans
      of 102 pedicle screws placed through a mature posterolateral fusion mass (n = 10
      [T10-T12]; n = 92 [L1-S1]) were independently assessed and compared with a
      matched control (nonobscured anatomy) group. All screws were placed before any
      decompression using the FluoroNav system. RESULTS: In the fusion mass group,
      overall 81.4% of screws were completely within the pedicle. Seven medial and 12
      lateral pedicle breaches occurred. Relative to the total number of screws,
      pedicle breaches were graded II (<2 mm) in 13.5%, III (2-4 mm) in 2.9%, and IV
      (>4 mm) in 2.0% of screws. The number and direction of pedicle breaches were not
      significantly different when compared with the control group. There were no
      clinically significant screw misplacements in either group. CONCLUSIONS: The use
      of computer-assisted fluoroscopy is safe and effective for the placement of
      thoracolumbar (T10-S1) pedicle screws through a posterolateral fusion mass
      without performing laminoforaminotomies.

PMID- 17224818
TI  - Polyethylene wear debris and long-term clinical failure of the Charite disc
      prosthesis: a study of 4 patients.
AB  - STUDY DESIGN: A clinical case series of 4 patients undergoing anterior lumbar
      revision due to failure of total disc replacement surgery. OBJECTIVES: To assess
      the clinical significance of polyethylene wear debris in salvage surgery after
      initial total disc replacement, the pattern and the mechanisms of polyethylene
      wear in the retrieved cores, and the extent of polyethylene debris in the
      periprosthetic tissues obtained from 4 patients. SUMMARY OF BACKGROUND DATA:
      Previous in vitro wear tests have demonstrated low wear rates for lumbar
      artificial discs, suggesting that implant wear may not be a clinically relevant
      issue with total disc replacement. However, only long-term clinical
      investigations with analysis of retrieved implants and periprosthetic tissue can
      ultimately establish the significance of polyethylene wear debris for total disc
      arthroplasty. METHODS: Starting in 2004, we began routinely performing salvage
      procedures in patients with failed total disc replacements. We report on the
      short-term outcomes of 4 patients at our institution who were revised with a
      Charite prosthesis (DePuy Spine, Raynham, MA). Wear analysis of the retrieved
      prosthesis and histologic examination of the periprosthetic tissue were also
      performed. RESULTS: All of the retrieved polyethylene cores showed evidence of
      wear, but the extent and severity varied among the 4 patients. Wear and fracture
      of the core were associated with osteolysis of the underlying sacrum in 1
      patient. Histologic examination of the periprosthetic tissues confirmed the
      presence of wear debris lying in inflammatory fibrous tissue. In 3 of the 4
      patients, implant wear was associated with an unfavorable biomechanical
      environment (e.g., subsidence, migration, undersizing, and adjacent fusion). The
      mechanisms of wear included adhesive/abrasive wear of the central domed region of
      the polyethylene core, as well as chronic rim impingement, resulting in rim
      fatigue and fracture. CONCLUSIONS: This study demonstrates the clinical
      significance of polyethylene wear debris and the potential for osteolysis with
      total disc replacements. The authors recommend that patients undergoing lumbar
      disc arthroplasty receive long-term follow-up to monitor the wear and functional
      status of their implants.

PMID- 17224819
TI  - Risk factors for the development of perioperative complications in elderly
      patients undergoing lumbar decompression and arthrodesis for spinal stenosis: an
      analysis of 166 patients.
AB  - STUDY DESIGN: Retrospective review. OBJECTIVE: To quantify and describe
      perioperative complication rates in a large series of well-matched elderly
      patients who underwent lumbar decompression and arthrodesis. SUMMARY OF
      BACKGROUND DATA: Posterior lumbar decompression and fusion is frequently
      performed to treat lumbar stenosis with instability. An increasing number of
      elderly patients are undergoing operative treatment for degenerative lumbar
      disease. The reported morbidity of performing decompression and arthrodesis in
      this population varies widely in the literature, with recent reports showing a
      high rate of major complications. METHODS: A total of 166 patients age 65 or
      older that underwent primary posterior lumbar decompression and fusion with
      (group 1; n = 75) or without (group 2; n = 91) instrumentation were included.
      Hospital records were reviewed for the occurrence of any complications (major and
      minor), the need for transfusion, estimated length of stay, and disposition at
      discharge. Logistic regression (with the presence/absence of major complications
      as the dependent variable) was used to identify risk factors for the occurrence
      of a complication. RESULTS: Five major complications (3%) occurred (group 1, 1;
      group 2, 4). Minor complications developed in 30.7% of group 1 and 31.9% of group
      2. There were no deaths, and only one perioperative complication was attributable
      to the use of instrumentation. Decompression/fusion of 4 or more segments was
      significantly associated with the occurrence of a major complication. Advanced
      age, the presence of medical comorbidities, or the use of instrumentation did not
      increase the rate of major or minor complications. The occurrence of either a
      major or minor complication prolonged hospital stay. CONCLUSIONS: Posterior
      lumbar decompression and fusion can be safely performed in elderly patients, with
      a low rate of major complications. The addition of instrumentation does not
      increase the complication rate. These results differ from those previously
      reported in the literature, which describe a significantly higher rate of
      complications in this age group, with a prolonged rate of hospitalization.

PMID- 17224820
TI  - Acupuncture for neck disorders.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To determine the effects of
      acupuncture for individuals with neck pain. SUMMARY OF BACKGROUND DATA: Neck pain
      is one of the 3 most frequently reported complaints of the musculoskeletal
      system. Treatments for neck pain are varied, as are the perceptions of benefits.
      METHODS.: We searched CENTRAL (2006, issue 1) and MEDLINE, EMBASE, MANTIS,
      Cumulative Index to Nursing and Allied Health Literature from their beginning to
      February 2006. We searched reference lists and the acupuncture database TCMLARS
      in China. Any published trials using randomized (RCT) or quasi-randomized (quasi
      RCT) assignment to the intervention groups, either in full text or abstract form,
      were included. RESULTS: We found 10 trials that examined acupuncture treatments
      for chronic neck pain. Overall, methodologic quality had a mean of 2.3 of 5 on
      the Jadad scale. For chronic mechanical neck disorders, there was moderate
      evidence that acupuncture was more effective for pain relief than some types of
      sham controls, measured immediately posttreatment. There was moderate evidence
      that acupuncture was more effective than inactive, sham treatments measured
      immediately posttreatment, and at short-term follow-up (pooled standardized mean
      difference, -0.37; 95% confidence interval, -0.61 to -0.12). There was limited
      evidence that acupuncture was more effective than massage at short-term follow
      up. For chronic neck disorders with radicular symptoms, there was moderate
      evidence that acupuncture was more effective than a wait-list control at short
      term follow-up. CONCLUSIONS: There is moderate evidence that acupuncture relieves
      pain better than some sham treatments, measured at the end of the treatment.
      There is moderate evidence that those who received acupuncture reported less pain
      at short-term follow-up than those on a waiting list. There is also moderate
      evidence that acupuncture is more effective than inactive treatments for
      relieving pain posttreatment, and this is maintained at short-term follow-up.

PMID- 17224821
TI  - High-field magnetic resonance imaging of meniscoids in the zygapophyseal joints
      of the human cervical spine.
AB  - STUDY DESIGN: Prospective in vitro study of meniscoids in the cervical
      zygapophysial joints. OBJECTIVES.: To assess the use of high-field magnetic
      resonance imaging (MRI) as a potential tool for evaluating meniscoids of the
      cervical zygapophysial joints. SUMMARY OF BACKGROUND DATA: Pain originating from
      the cervical spine is a frequent condition. It has been suggested that pathologic
      conditions of meniscoids within the zygapophysial joints may cause pain. METHODS:
      Six zygapophysial joints from one embalmed human body were investigated with a
      3.0-T MR unit, equipped with a microimaging-set. MRIs were correlated with
      microanatomical sections. RESULTS: High-quality images of the meniscoids were
      obtained for all joints examined. There was a good correlation between the
      anatomic features derived from MRI and the microanatomical sections. CONCLUSIONS:
      High-field MRI was successfully implemented as a noninvasive method for imaging
      the meniscoids in cervical zygapophysial joints. The results of this in vitro
      study indicate that high-field MRI may be feasible in evaluating patients with
      cervical pain possibly related to meniscoid pathology.

PMID- 17224822
TI  - The long-term effect of multidisciplinary back training: a systematic review.
AB  - STUDY DESIGN: Systematic review of randomized controlled trials. OBJECTIVES: To
      determine the long-term effect of multidisciplinary back training on the work
      participation of patients with nonspecific chronic low back pain. SUMMARY OF
      BACKGROUND DATA: Chronic low back pain is influenced by multiple factors.
      Multidisciplinary back training represents one of the options to take this
      multiplicity into account. So far, only evidence of the short-term effectiveness
      of this approach in terms of work participation is available. METHODS: Electronic
      databases were searched and the references of various articles were screened for
      relevant publications. Ten studies met the inclusion criteria. All included
      studies were evaluated for their methodologic quality. RESULTS: Five of the
      studies had a low methodologic quality. All high-quality studies found a positive
      effect on at least one of the 4 outcome measures used. Based on our criteria,
      effectiveness was found for the outcome measures of work participation and
      quality of life. No effectiveness was found for experienced pain and functional
      status. The intensity of the intervention seems to have no substantial influence
      on the effectiveness of the intervention. CONCLUSION: In the long-term,
      multidisciplinary back training has a positive effect on work participation in
      patients with nonspecific chronic low back pain.

PMID- 17224823
TI  - Patients' satisfaction with provided care/information and expectations on
      clinical outcome after lumbar disc herniation surgery.
AB  - STUDY DESIGN: A prospective study of patients undergoing lumbar disc herniation
      surgery. OBJECTIVES: To assess patients' satisfaction with care/preoperative
      information, if expectations on surgical results and ability to return to work
      are related to baseline characteristics, and/or can predict self-reported
      outcome. Self-reported outcome was compared with objective outcome. SUMMARY OF
      BACKGROUND DATA: Patients' expectations on treatment results have been discussed
      as a predictive factor for postoperative outcome and satisfaction demonstrated to
      be directly related to patient expectations. METHODS: The study includes 148
      patients, 46% women, mean age 40 (range 18-66). Before and 2 years after surgery,
      questionnaires about given information/care, expected/present work ability, and
      expectations on/obtained improvement of physical functions/symptoms (leg and back
      pain, sensibility, and muscle function) were filled in. The visual analog scale
      leg pain, Zung Depression Scale, and Oswestry Disability Index were used as
      baseline characteristics. At 2-year follow-up, self-reported and objective
      outcome was assessed. RESULTS: Satisfaction with given information/care were
      reported by 46% and 82%, respectively. Zung Depression Scale related to
      expectations on leg pain recovery (P = 0.022), work ability (P = 0.046), and
      satisfaction with given information (P = 0.031). Patients who expected to return
      (76%) and not return (24%) to work, returned in 78% and 26%, respectively (P =
      0.021). A high agreement between self-reported outcome and objective outcome were
      found (P < 0.001). CONCLUSIONS: Patients undergoing lumbar disc herniation
      surgery are mostly satisfied with provided care before and after surgery,
      however, less satisfied with information provided. Further, patients with
      preoperative positive expectations on work return and realistic expectations on
      pain and physical recovery have a greater chance to be satisfied with the
      surgical results.

PMID- 17224824
TI  - The impact of psychosocial factors on low back pain: longitudinal results from
      the Belstress study.
AB  - STUDY DESIGN: An epidemiological cohort study. OBJECTIVE: To describe the impact
      of psychosocial factors, both work and nonwork-related, on the prevalence of low
      back pain (LBP) after 6.6 years on average. SUMMARY OF BACKGROUND DATA: There is
      growing consensus that psychosocial factors play a role in the development of
      LBP, although results are not consistent across studies. METHODS: Within a sample
      of 2556 middle-aged men and women from the Belstress study, baseline psychosocial
      factors were measured through self-administered questionnaires and related to
      prevalent cases of LBP after a mean time interval of 6.6 years through Cox
      regression analysis. RESULTS: After adjustment for individual and physical risks,
      including occasional back pain at baseline, the prevalence rate of LBP in men is
      significantly related to baseline low decision latitude and low social support at
      work, and nonsignificantly to high job strain, low wage and job satisfaction,
      feeling stressed at work, and feeling depressed. High job insecurity, feeling
      stressed at work, and feeling depressed nonsignificantly increase the relative
      risks for LBP in women. CONCLUSIONS: Based on the results of this study,
      psychosocial factors (both work and nonwork-related) constitute nonnegligible
      risks for the development of LBP.

PMID- 17224825
TI  - Emotional distress as a predictor for low back disability: a prospective 12-year
      population-based study.
AB  - STUDY DESIGN: A population-based, prospective cohort. OBJECTIVE: To study
      associations between emotional distress and long-term low back disability in a
      general population. SUMMARY OF BACKGROUND DATA: In primary and hospital care
      studies, emotional, cognitive, and personality factors have been associated with
      low back disability, while the association between distress and novel back pain
      episodes has been uncertain. METHODS: A randomly drawn cohort of 1152
      occupationally active persons aged 20-55 years was interviewed with a
      comprehensive psychosocial questionnaire in 1990, and was followed for 12 years
      in national registers over sickness, rehabilitation, and disability benefits.
      Data on emotional distress, earlier low back pain (LBP), education, life style,
      psychosocial, and work-related factors were collected at baseline. RESULTS: Long
      term benefits due to low back disability were granted to 131 persons (11.4%) in
      the follow-up period. In multivariate analysis, earlier LBP, emotional distress,
      low grade of education, and high physical job stress were associated with low
      back disability. Persons with both emotional distress and earlier back pain were
      most at risk for disability (hazard ratio 2.91, 95% confidence interval 1.60
      5.29). Persons with emotional distress but no earlier episodes of LBP had no
      increased risk for low back disability (hazard ratio 0.71, 95% confidence
      interval 0.34-1.45). CONCLUSIONS: Emotional distress is a predictor for low back
      disability in persons with earlier LBP, but not in persons without. To prevent
      low back disability, emotional distress should be considered and treated in
      persons with LBP.

PMID- 17224826
TI  - Avoiding neurologic complications following ligation of the segmental vessels
      during anterior instrumentation of the thoracolumbar spine.
AB  - STUDY DESIGN: A retrospective evaluation of anterior instrumentation of the
      vertebral bodies in the thoracolumbar spine. OBJECTIVE: To evaluate the
      possibility of preserving the segmental vessels following anterior
      instrumentation. SUMMARY OF BACKGROUND DATA: Occlusion of the segmental vessels,
      routinely performed during anterior spine instrumentation, might cause neurologic
      injury secondary to cord ischemia. METHODS: The medical data of 29 patients
      following anterior instrumentation of the vertebral bodies at the thoracolumbar
      spine were reviewed. All underwent surgery recently when we decided to preserve
      the segmental vessels whenever possible. We sought the reasons that enabled us to
      do so regarding age, gender, underlying pathology, surgical technique, operation
      duration, instrumentation type and size, and location in the vertebral body.
      RESULTS: In only 7 patients, fused between T10 and L5, were we able to preserve
      the segmental vessels. All were instrumented with one 6.25-7-mm wide screw in
      each vertebral body connected by one rod, approximately half the screws above and
      half below the segmental vessels. In 22 patients, we were unable to preserve the
      vessels due to the need to insert 2 screws or a large threaded wide vertebral
      cage into each vertebra. CONCLUSIONS: There is adequate space anteriorly in the
      vertebral body, above and below the segmental vessels, for the insertion of one
      screw, even with staples.

PMID- 17224827
TI  - Translaminar microsurgical approach for lumbar herniated nucleus pulposus (HNP)
      in the "hidden zone": clinical and radiologic results in a series of 24 patients.
AB  - STUDY DESIGN: Clinical series. OBJECTIVE: To describe an alternative surgical
      approach for disc herniations in the "hidden zone." SUMMARY OF BACKGROUND DATA:
      Many spine surgeons have suggested different surgical approaches for symptomatic
      preforaminal and foraminal disc herniations. However, almost every surgical
      approach has certain shortcomings when it comes to exposing the "hidden zone"
      without causing some degree of spinal instability. METHODS: Twenty-four patients
      with preforaminal and foraminal disc herniation underwent surgical treatment via
      a translaminar microsurgical approach. RESULTS.: Excellent results were obtained
      in all patients in terms of pain relief, and all had improvement in motor
      strength except for 1 patient. No spinal instability was seen at the latest
      follow-up. CONCLUSIONS: A classic interlaminar interspace approach combined with
      a very limited translaminar fenestration seem to be an acceptable surgical method
      for accessing a preforaminal disc herniation, and this technique has proven to be
      safe and did not cause any instability at the latest follow-up.

PMID- 17224828
TI  - Re: Yoshida et al. Comparison of the anatomical risk for vertebral artery injury
      associated with the C2-pedicle screw and atlantoaxial transarticular screw. Spine
      2006;31:E513-7.

PMID- 17224829
TI  - Re: Reindl R, Ouellet J, Harvey EJ, et al. Anterior reduction for cervical spine
      dislocation. Spine 2006;31:648-52.

PMID- 17224830
TI  - Re: Hughes SS, Pringle T, Phillips F, et al. Settling of fibula grafts following
      multilevel anterior cervical corpectomy. A radiographic evaluation. Spine
      2006;31:1911-5.

PMID- 17224832
TI  - Re: Carragee EJ, Lincoln T, Parmar VS, et al. A gold standard evaluation of the
      'discogenic pain' diagnosis as determined by provocative discography. Spine
      2006;31:2115-23.

PMID- 17224833
TI  - The Roland-Morris Disability Questionnaire.

PMID- 17224835
TI  - Early revision for component malrotation in total knee arthroplasty.
AB  - Component malrotation may result in unsuccessful total knee arthroplasty. We
      asked whether revision improves function in patients with malrotated total knee
      arthroplasty components. We retrospectively reviewed 22 revision total knee
      arthroplasties performed for femoral and/or tibial component malrotation.
      Revision surgery was performed within 2 years of the primary arthroplasty in 81%
      of the cases (18 of 22) with the remainder within 5 years. Although all patients
      had pain, 32% of patients had associated instability and 36% of patients had poor
      range of motion. Average Knee Society Scores improved from 42 preoperatively to
      77 postoperatively. Average Oxford Knee Scores improved from 38 preoperatively to
      29 postoperatively. Although clinical and functional improvement was observed,
      these results are inferior to those for primary knee arthroplasty, and they
      emphasize the need for proper component rotational positioning during primary
      total knee arthroplasty. Internal component malrotation leads not only to
      patellofemoral problems, but also to difficulty in gap balancing and femoral
      component sizing, which may in turn lead to either poor range of motion or
      symptoms of knee instability.

PMID- 17224836
TI  - Incidence of fracture-healing complications after femoral neck fractures.
AB  - What is the relationship between the age or gender of the patient and the
      incidence of fracture-healing complications after internal fixation of
      intracapsular fractures? We aimed to determine the association between the age of
      the patient and fracture nonunion and also to establish if the gender of the
      patient had any influence on the occurrence of fracture nonunion. We
      prospectively studied 1133 patients with intracapsular fractures of the femoral
      neck treated by internal fixation. The overall incidence of nonunion was 19.3%.
      Fracture nonunion was less common for undisplaced fractures than for displaced
      fractures (48 of 565 [8.5%] versus 171 of 568 [30.1%]) and in men than in women
      (35 of 271 [12.9%] versus 184 of 862 [21.3%]). The incidence of nonunion
      progressively increased with age from one of 17 (5.9%) in patients younger than
      40 years to 84 of 337 (24.9%) in patients in their 70s. For patients in their
      80s, the incidence of nonunion began to decrease, but if patients who died within
      1 year after injury were excluded, the incidence continued to increase. Our study
      showed an increased risk for intracapsular hip fractures developing nonunion with
      older age and in females.

PMID- 17224837
TI  - Reconstructing proximal humeral fractures using the bicipital groove as a
      landmark.
AB  - Controversy persists in the literature regarding the use of the bicipital groove
      as an anatomic landmark to restore humeral head retroversion when treating
      complex proximal humeral fractures with arthroplasty. We quantified the three
      dimensional geometry of the bicipital groove in 49 dried humeri relative to the
      intramedullary axis, quantified the reliability of using the bicipital groove as
      an anatomic landmark, and compared this reliability with that of the conventional
      technique that uses a fixed, average angle relative to the epicondylar axis to
      establish humeral head retroversion. The data show the anterior offset of the
      bicipital groove is nearly constant from proximal (7.3 mm +/- 2.8 mm) to distal
      (7.2 mm +/- 1.5 mm) relative to the intramedullary axis. Given the consistency,
      the distal bicipital groove (at the level of the surgical neck) is a reasonable
      landmark to establish humeral head retroversion after complex proximal humeral
      fractures having reliability (angular error of 7.9 degrees +/- 5.8 degrees) as
      good as or better than the conventional fixed-angle technique.

PMID- 17224839
TI  - Psychologic reasons for patients preferring minimally invasive total hip
      arthroplasty.
AB  - Success of an orthopaedic operation depends on patients achieving their primary
      goal(s) and having satisfaction with the outcome. The enthusiasm of patients for
      minimally invasive total hip arthroplasty seems related to satisfaction with the
      operation. We hypothesized patients' attitude toward a small incision would
      increase their confidence and satisfaction with the operation but the importance
      of the incision would dissipate after patients realized their goals of pain
      relief and functional recovery. One hundred sixty-five patients responded to a 14
      question patient-perception questionnaire preoperatively and 6 weeks
      postoperatively and a followup survey at 6 months to 1 year postoperatively. One
      hundred nine patients had small incisions (mean, 9.6 cm) and 56 had long
      incisions (mean, 17.9 cm). Preoperatively patients expected small-incision
      surgery would positively influence their primary goals and satisfaction; at 6
      weeks postoperative they believed more strongly that this was true. By 6 months
      to 1 year, the importance of the incision diminished because 100% of patients met
      their primary goals. Forty percent of patients with a long incision were not
      satisfied and the reasons given were related to the process of reincorporating
      their injured hip into their whole-body image. We confirmed our first hypothesis
      that a small incision influences a patient's satisfaction postoperatively; we
      could not confirm our second hypothesis that incision length did not matter after
      attaining primary goals.

PMID- 17224840
TI  - Experimental joint contracture correction with low torque--long duration repeated
      stretching.
AB  - Tension is necessary to maintain and restore the mechanical properties of soft
      connective tissues. Conversely, reduced tension states such as produced by
      immobilization weaken mechanical properties and facilitate joint contracture. We
      assessed the effect of low torque-long duration stretching to increase the range
      of motion (ROM) and to restore the mechanical properties of contracted joints in
      66 rat knees immobilized for 40 days. After remobilization, we randomly divided
      the contracted knees into four treatment groups treated with repeated stretches
      of diverse torques and duration: stretching with low-torque and long-duration,
      high-torque and short-duration, high-torque and long-duration, low-torque and
      short duration. We included control and natural recovery groups. Phase lag in all
      treatment groups recovered to the same range as in the normal controls. Dynamic
      stiffness, which was not altered by joint immobilization, increased in all
      treatment groups. Deformation and load to failure improved substantially only in
      the low-torque and long-duration stretching group. Low-torque and long-duration
      repeated stretching leads to a greater restoration of ROM with more normal
      mechanical properties compared to high-torque and short duration stretching.

PMID- 17224841
TI  - Distinct inflammatory gene pathways induced by particles.
AB  - The biologic response to particulate load after arthroplasty has not been fully
      characterized but is believed mediated by proinflammatory cytokines released from
      mononuclear cells in the periprosthetic region. To investigate the contribution
      of lymphocytes to expression of proinflammatory genes induced by metal particles,
      we compared gene expression of mononuclear cells in response to metal and
      polymethylmethacrylate particles using cDNA microarray profiling. Peripheral
      blood mononuclear cells and monocytes were stimulated with polymethylmethacrylate
      and titanium particles of clinically relevant sizes. Polymethylmethacrylate
      elicited a six- to 12-fold increase in gene expression of tumor necrosis factor
      alpha, interleukin 1alpha, interleukin 1beta, interleukin 6, and interleukin 8 in
      purified monocytes and unfractionated peripheral blood mononuclear cells.
      Although the effect of titanium on stimulation of purified monocytes was modest,
      stimulation of lymphocyte-containing peripheral blood mononuclear cells by
      titanium particles resulted in monocyte-derived proinflammatory cytokine
      expression. In contrast to polymethylmethacrylate, titanium particles stimulated
      increased expression of T lymphocyte-derived cytokines, including interleukin 2,
      interferon gamma, interleukin 9, and interleukin 22, in peripheral blood
      mononuclear cell cultures. The induction of T cell activation by titanium
      particles suggests lymphocytes may contribute to the inflammation that mediates
      osteolysis in patients with metallic particulate debris after total joint
      replacement.

PMID- 17224842
TI  - Development of the McGill Range of Motion Index.
AB  - We created the McGill Range of Motion Index (McROMI) to allow us to ascribe a
      score to global limited range of motion (ROM) in patients with polyarthritis. Our
      goal was to have an easy-to-use index that required only visual estimation of ROM
      and could be performed by allied health professionals with limited training. The
      index was created with a range of motion ranking technique involving
      rheumatologists at McGill University and its validity was tested in patients with
      early inflammatory arthritis in the McGill Early Arthritis Registry. We
      hypothesized a valid index would correlate with various process and outcome
      measures. We found correlations between the McROMI and function (Health
      Assessment Questionnaire), Health Related Quality of Life (SF-36), pain, a global
      assessment of inflammatory disease activity (DAS28), and the number of tender and
      swollen joints. The McROMI demonstrates good validity as a measure of ROM in
      early inflammatory arthritis. It will prove useful in future research as a means
      of controlling for ROM as a confounder of various outcomes and in studies of
      therapeutic maneuvers to improve ROM.

PMID- 17224843
TI  - Applications of nanotechnology in orthopaedics.
AB  - Nanotechnology is the application of science and engineering at the nanoscale. A
      diverse range of applications are beginning to emerge in all areas of medicine.
      We performed a survey from November 2005 to March 2006 using the Internet search
      engines PubMed, ScienceDirect, ISI Web of Knowledge, and Google Scholar. We
      report on the role of nanotechnology in orthopaedics, exploring current and
      potential applications. Nanostructured materials have been proposed as the next
      generation of orthopaedic implant properties by creating a surface environment
      more conducive for osteoblast function. Bone substitute materials, whose
      nanoscale composition emulates the hierarchic organization of natural bone, shows
      initiation of the desirable formation of an apatite layer. Nanotechnology also
      has been harnessed to improve the cutting performance and quality of surgical
      blades. Postoperative infection rates may be reduced by using nanofibrous
      membrane wound dressings containing antibacterial properties. The most notable
      application of nanotechnology in orthopaedics may be drug delivery, including
      nanotherapeutics for treating bone cancer and arthritis. Nanotechnology is being
      used in orthopaedics, and likely will play a valuable role in future
      developments.

PMID- 17224844
TI  - Effect of clinical pharmacists on utilization of and clinical response to
      antiretroviral therapy.
AB  - OBJECTIVE: To determine the association of clinical pharmacists with health
      outcomes and utilization measures among HIV-infected patients. METHODS:
      Observational study of 1571 HIV-infected patients prescribed their initial highly
      active antiretroviral therapy (HAART) regimen in clinics with and without a
      clinical pharmacist. Outcomes analyzed were changes in plasma HIV RNA level, CD4
      T-cell counts, and service utilization (hospital days, emergency department
      visits, and office visits) over 24 months based on exposure to a clinical
      pharmacist. RESULTS: Patients exposed to a clinical pharmacist tended to be more
      likely to achieve an HIV RNA level <500 copies/mL at 12 months (adjusted odds
      ratio [OR] = 2.01, 95% confidence interval [CI]: 0.92 to 4.37). At 24 months,
      however, results depended on the provider panel size; the ORs for panel sizes <
      or =50 and >50 HIV-infected patients were 1.67 (95% CI: 0.60 to 4.62) and 0.97
      (95% CI: 0.39 to 2.41), respectively. CD4 T-cell counts were modestly but
      nonsignificantly higher for the patients exposed to a clinical pharmacist.
      Utilization also depended on the provider panel size; pharmacist exposure was
      associated with 64% (95% CI: 30% to 108%) and 9% (95% CI: -11% to 33%) increases
      in total hospital days for panel sizes < or =50 and >50 HIV-infected patients,
      respectively. Pharmacist exposure was also associated with a 19% (95% CI: -13% to
      -24%) decrease in office visits for panel sizes < or =50 HIV-infected patients,
      with minimal effect for larger panel sizes. CONCLUSION: Clinical pharmacists seem
      to contribute to lower office visit rates in antiretroviral-naive patients
      initiating HAART.

PMID- 17224845
TI  - Genotypic resistance of archived and circulating viral strains in the blood of
      treated HIV-infected individuals.
AB  - The aim of this study was to evaluate patterns of antiretroviral resistance of
      HIV-1 in peripheral blood mononuclear cells (PBMCs) and in the plasma of patients
      whose therapeutic regimen is failing. Plasma and PBMC samples were collected from
      95 HIV-infected patients undergoing long-term treatment. Genotyping of the
      reverse transcriptase (RT) and protease genes of HIV-1 was undertaken using the
      fluorescent dideoxy-terminator method. Comparison of the amino acid sequence of
      the RT and protease genes in cell-associated variants of HIV-1 with that of the
      plasma revealed that 62 of the 95 patients' samples tested exhibited different
      genotypic resistance patterns (discordant samples [DSs]). In 27% of samples, the
      patterns of resistance detected were concordant in both compartments. In 51% of
      DSs, the greatest number of mutations was found in plasma; however, in 37% of
      DSs, greater numbers of mutations were found in PBMC DNA. The HIV mutation
      patterns detected in plasma do not necessarily reflect those found in the cell
      associated compartment. The observation that the cellular compartment may contain
      an archive of the resistance variant makes this reservoir an interesting
      substrate for analysis of the "resistance potential" in a given patient.

PMID- 17224846
TI  - Early initiation of antiretroviral therapy: the current best way to reduce liver
      related deaths in HIV/hepatitis C virus-coinfected patients.
AB  - Approximately 25% to 35% of HIV-infected persons in developed countries are
      coinfected with hepatitis C virus (HCV). HCV liver disease is accelerated by HIV
      coinfection, especially at low CD4 cell counts. Highly active antiretroviral
      therapy (HAART) dramatically reduces HIV-related mortality, and liver disease has
      emerged as a major cause of death in HIV/HCV-coinfected persons. Anti-HCV therapy
      with pegylated interferon plus ribavirin can cure HCV infection in up to 40% of
      coinfected patients; however, only approximately 10% of coinfected patients are
      considered candidates. Hence, HCV therapy cures approximately 4% of coinfected
      patients. Eleven cohort studies have shown that HAART is associated with a
      reduced rate of progression of HCV liver disease, and 4 of these studies have
      demonstrated a reduction in liver-related mortality. Although offering HCV
      therapy to the few eligible HIV/HCV-coinfected patients is important, early
      initiation of HAART in coinfected patients has a greater public health impact in
      reducing liver-related mortality than in curing HCV infection in approximately 4%
      of these patients.

PMID- 17224847
TI  - Hepatitis B virus genotypes and lamivudine resistance mutations in HIV/hepatitis
      B virus-coinfected patients.
AB  - BACKGROUND: Differences in subtypes, hepatitis B early antigen (HBeAg)-negative
      variants, and drug resistance mutations all seem to influence the clinical and
      therapeutic outcome in patients with chronic hepatitis B virus (HBV) infection.
      Information available on the prevalence and distribution of distinct HBV variants
      in HIV-positive patients is scarce. METHODS: All HIV-infected patients with
      persistent serum hepatitis B surface antigen and detectable HBV viremia were
      identified in a reference HIV clinic located in Madrid, Spain. HBV load,
      subtypes, precore (PC) and basal core promoter (BCP) variants, and lamivudine
      (LAM) resistance mutations were analyzed. RESULTS: A total of 81 HBV/HIV
      coinfected patients (4.1%) were identified in a population of 1968 HIV-positive
      patients. Plasma specimens with detectable HBV viremia could be obtained from 62
      subjects, and this was the study population that underwent further virologic
      characterization. HBV genotype distribution was as follows: A (n = 27), D (n =
      27), E (n = 1), F (n = 2), and G (n = 3). Two patients had mixed HBV genotypes
      (A/E and A/F). HBV subtype A was predominant (74%) among patients infected
      through sexual contact, whereas HBV-D was most frequent (74%) among intravenous
      drug users (P < 0.001). PC/BCP mutants were more frequent in patients with HBV-D
      than in those with HBV-A (63% vs. 18%; P < 0.01). Median time on LAM was 40
      months; patients with HBV-A tended to show LAM resistance mutations more often
      (53% vs. 44%) and to develop them earlier (35 vs. 45 months) than patients with
      HBV-D. The dual L180M + M204V/I mutant was the predominant resistance pattern,
      although a triple rt173V + 180M + 204V, which acts as a vaccine escape mutant,
      was found in 1 individual. In the multivariate analysis, patients with LAM
      resistance mutations were significantly more frequently HBeAg-positive and older
      than individuals with wild-type HBV. Hepatitis-delta was recognized in 13 (21%)
      of these 62 HBV viremic patients, with no association with specific HBV variants.
      CONCLUSION: Risk transmission group, age, and positive serum HBeAg are the main
      determinants of distinct HBV virologic variants, including HBV genotypes and LAM
      resistant mutants, in HBV/HIV-coinfected patients.

PMID- 17224848
TI  - The tablet formulation of lopinavir/ritonavir provides similar bioavailability to
      the soft-gelatin capsule formulation with less pharmacokinetic variability and
      diminished food effect.
AB  - Lopinavir, an HIV protease inhibitor, is coformulated with ritonavir to enhance
      the bioavailability and pharmacokinetics of lopinavir. The original solid oral
      formulation of lopinavir/ritonavir, a soft-gelatin capsule (SGC), requires
      refrigerated storage, is taken as 6 capsules daily at the recommended adult dose,
      and is administered with food to maximize the bioavailability of lopinavir. Melt
      extrusion technology was used to produce a tablet formulation reducing the number
      of dosage units administered per day and simplifying storage requirements. Three
      studies assessed the bioavailability of tablet doses of lopinavir/ritonavir at
      800/200 mg or 400/100 mg under different meal conditions compared with equal
      doses of the SGC after a moderate-fat meal. The tablet was bioequivalent to the
      SGC after a moderate-fat meal with respect to lopinavir and ritonavir areas under
      the concentration-time curve. Compared with the SGC formulation, the tablet
      formulation resulted in more consistent lopinavir and ritonavir exposures within
      and across studies and across meal conditions. The diminished food effect and
      decreased variability of the tablet are likely to result in more consistent
      lopinavir and ritonavir exposures, minimizing the likelihood of extreme high or
      low values compared with the SGC.

PMID- 17224849
TI  - The diagnosis and treatment of HIV-infected children in China: challenges and
      opportunities.
AB  - BACKGROUND: HIV-infected children in China have not been well studied. This
      national survey describes the demographic characteristics and the associated
      diagnostic and antiretroviral treatment (ART) efforts directed toward surviving
      HIV-infected children. METHODS: A cross-sectional study was conducted in the 6
      provinces with the highest HIV prevalence: 4 former plasma donation (FPD)
      provinces and 2 intravenous drug use (IDU) provinces. A survey on demographics
      and treatment-related issues was distributed to the parents or guardians of all
      living HIV-infected children identified through the national case reporting
      system. Descriptive and bivariate analyses were performed on completed surveys.
      RESULTS: Six hundred ninety-two (62.4%) of the total 1108 surveys were returned,
      and 650 were eligible for analysis. The average age in FPD provinces (mean +/-
      SD: 8.1 +/- 3.2 years) was significantly older than in IDU provinces (mean +/-
      SD: 5.4 +/- 2.2 years; P < 0.001). The average lag time from the probable date of
      transmission to a diagnosis for patients with mother-to-child transmission (MTCT)
      was 6.7 +/- 3.1 years in the FPD provinces and 4.7 +/- 1.9 years in the IDU
      provinces (P < 0.001). On the basis of the CD4 cell count or World Health
      Organization staging, 29.8% (144 of 484) of children from all 6 provinces who
      were not on ART needed it. CONCLUSIONS: This first national pediatric survey
      indicates that the age and time required for diagnosis were greater in HIV
      infected children from FPD provinces compared with those from IDU provinces. In
      addition, this survey highlights the prolonged delay in the diagnosis and
      initiation of ART for children in China. Aggressive efforts to identify HIV
      positive pregnant women, scale up prevention of MTCT activities, and expand early
      diagnosis and treatment are urgently needed.

PMID- 17224850
TI  - Detecting unsuspected HIV infection with a rapid whole-blood HIV test in an urban
      emergency department.
AB  - OBJECTIVE: To evaluate and compare HIV screening and provider-referred diagnostic
      testing as strategies for detecting undiagnosed HIV infection in an urban
      emergency department (ED). METHODS: From January 2003 through April 2004, study
      staff offered HIV screening with rapid tests to ED patients regardless of risks
      or symptoms. ED providers could also refer patients for diagnostic testing.
      Patients aged 18 to 54 years without known HIV infection were eligible. RESULTS:
      Of 4849 eligible patients approached for screening, 2824 (58%) accepted and were
      tested; 414 (95%) of 436 provider-referred patients accepted and were tested.
      Thirty-five (1.2%) screened patients and 48 (11.6%) provider-referred patients
      were infected with HIV (P < 0.001). Of these, 18 (51%) screened patients and 24
      (50%) referred patients reported no traditional risk factors; 27 (77%) screened
      patients and 38 (79%) referred patients entered HIV care. Of HIV-infected
      patients with CD4 cell counts available, 14 (45%) of 31 screened patients and 37
      (82%) of 45 provider-referred patients had <200 cells/microL (P < 0.001).
      CONCLUSIONS: ED screening detects HIV infection and links to care patients who
      may not be tested through risk- or symptom-based strategies. The diagnostic yield
      was higher among provider-referred patients, but screening detected patients
      earlier in the course of disease.

PMID- 17224851
TI  - Lack of perceived sleep improvement after 4-month structured exercise programs.
AB  - OBJECTIVE: Many middle-aged women experience decreases in their sleep quality
      during the menopausal transition. Physical activity has been shown to improve
      sleep, but few randomized, controlled trials investigating such effects in this
      population exist. In 164 previously low-active middle-aged women (mean age =
      49.9, SD = 3.6), using a 4-month randomized, controlled trial, we examined
      structured exercise in the form of walking or yoga to determine the effects on
      perceived sleep quality. DESIGN: Participants completed body composition and
      fitness assessments and a battery of psychological measures, including the
      Pittsburgh Sleep Quality Index, at the beginning and end of a 4-month randomized,
      controlled exercise trial with three arms: walking, yoga, and control. RESULTS: A
      series of mixed-model repeated-measures univariate analyses of covariance did not
      reveal any statistically significant intervention effects for total sleep quality
      or any individual sleep-quality domain. The pattern of effect sizes indicated
      that the walking group tended to experience small improvements in five of the
      seven assessed sleep-quality domains. Residual changes in menopausal symptoms and
      depression were associated with residual changes in total sleep quality. However,
      after controlling for the effects of physical activity, only menopausal symptoms
      contributed a unique amount of variance in residual change in total sleep
      quality. CONCLUSIONS: In this study, 4-month moderate-intensity walking and low
      intensity yoga programs were ineffective in yielding statistically significant
      improvements in sleep quality. Exercise interventions of longer durations or
      greater intensity may be needed for such improvements.

PMID- 17224852
TI  - Levonorgestrel-releasing intrauterine system as an adjunct to estrogen for the
      treatment of menopausal symptoms--a review.
AB  - Exogenous estrogen is an effective means of prevention for postmenopausal
      symptoms. Estrogen treatment should be combined with progesterone in non
      hysterectomized women to prevent estrogen-induced malignant transformation of the
      endometrium. Progesterone supplementation using continuous combined estrogen +
      progesterone treatment may result in an increased incidence of breast cancer and
      cardiovascular disease. In addition, progesterone supplementation with sequential
      estrogen + progesterone treatment may cause immediate adverse effects, such as
      irregular bleeding and spotting, breast congestion, fluid retention, abdominal
      distention, and a change in lipid profile. All these effects are related, at
      least in part, to the progesterone component of the therapy.To avoid these
      complications, researchers are seeking safer progestational components and
      different modes of administration. In this article we review the findings on the
      use of the novel levonorgestrel-releasing intrauterine system as a therapeutic
      tool for localized, rather than systemic, progesterone administration in
      postmenopausal women.

PMID- 17224853
TI  - Interaction of obesity and skeletal bone mineral density in tooth retention in
      Japanese postmenopausal women.
AB  - OBJECTIVE: To investigate whether being overweight is associated with increased
      or decreased risk of tooth loss in Japanese postmenopausal women. DESIGN: The
      number of remaining teeth (total, anterior, and posterior teeth), mandibular bone
      height, and mandibular cortical mass were evaluated on the dental panoramic
      radiographs of 450 Japanese postmenopausal women. The bone mineral densities
      (BMDs) at the lumbar spine and femoral neck were measured by dual-energy x-ray
      absorptiometry. These measurements were compared among participants in three body
      mass index (BMI) categories (underweight, normal BMI, and overweight). RESULTS:
      Analysis of covariance adjusted for confounding variables revealed that
      participants who were overweight had a significantly lower number of total (P =
      0.019) and anterior (P = 0.012) remaining teeth than did those with normal BMI,
      although the former had significantly higher skeletal BMD values than the latter.
      No significant difference was observed in mandibular bone height between the
      overweight participants and those with normal BMI. There were no significant
      differences in the number of remaining teeth between the under- and overweight
      participants. Overweight participants had significantly higher skeletal BMDs (P <
      0.001) and tended to have larger mandibular cortical masses than those who were
      underweight. CONCLUSIONS: Despite their higher skeletal BMD, postmenopausal women
      who are overweight may have an increased risk of tooth loss, especially of the
      anterior teeth, compared with women who have normal BMI. This risk appears to be
      similar to that for underweight women.

PMID- 17224854
TI  - Endogenous androgen levels and cardiovascular risk profile in women across the
      adult life span.
AB  - OBJECTIVE: Whether endogenous androgen levels contribute to the cardiovascular
      disease (CVD) risk profile in women is controversial. The purpose of this study
      was to investigate systematically the relationships between serum levels of
      endogenous androgens and sex hormone-binding globulin (SHBG) and biochemical CVD
      risk profile, taking other known risk factors into account. DESIGN: This
      community-based cross-sectional study included 587 non-healthcare-seeking-women,
      aged 18 to 75 years, who were randomly recruited from the community via the
      electoral roll from April 2002 to August 2003. Participants were euthyroid; had
      no usage of exogenous steroids; had no history of tubal ligation, hysterectomy,
      or bilateral oophorectomy; and did not have hyperprolactinemia or polycystic
      ovarian syndrome. The relationships between total testosterone, SHBG, free
      testosterone, dehydroepiandrosterone sulfate, and androstenedione and high
      sensitivity C-reactive protein (CRP) and lipids were explored using linear
      regression with natural logarithm (ln) -or square root-transformed data as
      indicated. Issues of nonlinearity and interaction were addressed by the inclusion
      of extra regression terms where appropriate. We determined the change in the
      proportion of variation for each marker of the CVD risk profile explained by the
      addition of each hormone term to the models, having adjusted for age, body mass
      index, smoking, alcohol, and exercise. RESULTS: Menopausal status did not
      influence the statistical models for high-sensitivity CRP and high-density
      lipoprotein cholesterol, but for both low-density lipoprotein cholesterol and
      triglycerides, the proportion of variation explained by the models was
      substantially less in postmenopausal than in premenopausal women. Almost all of
      the highly statistically significant findings were related to the addition of the
      SHBG terms to the models. The changes in r2 values were highly statistically
      significant for the addition of the SHBG terms to the models for ln CRP and ln
      high-density lipoprotein for both pre- and postmenopausal women (P <= 0.01 and <
      0.001, respectively) and for ln triglycerides in postmenopausal (P < 0.001) and
      premenopausal women (P < 0.01). CONCLUSIONS: Endogenous testosterone and the
      adrenal preandrogens per se are not significant independent determinants of
      circulating high-sensitivity CRP or lipoprotein lipids. Our analyses provide
      further support for the independent predictive value of low SHBG levels for CVD
      risk profile and an independent contribution of the menopausal transition to the
      determination of low-density lipoprotein cholesterol and triglycerides.

PMID- 17224855
TI  - Effects of estradiol with oral or intravaginal progesterone on risk markers for
      breast cancer in a postmenopausal monkey model.
AB  - OBJECTIVE: To evaluate the effects of oral estradiol given with either oral or
      intravaginal micronized progesterone (P4) on risk biomarkers for breast cancer in
      a postmenopausal monkey model. DESIGN: This experiment was a two-way crossover
      study in which 20 ovariectomized adult female cynomolgus macaques were treated
      (in equivalent doses for women) with oral estradiol (1 mg/d) + oral micronized P4
      (200 mg/d) or intravaginal P4 delivered by Silastic rings (6- to 10-mg/d release
      rate). Hormone treatments lasted 2 months and were separated by a 1-month washout
      period. The primary outcome measure was breast epithelial proliferation. RESULTS:
      Serum P4 concentrations were significantly greater in subjects receiving oral P4
      (10.9 ng/mL) compared with intravaginal P4 (3.8 ng/mL) at 2 to 3 hours after oral
      dosing (P<0.0001) but not at 24 to 28 hours after oral dosing (2.9 ng/mL for oral
      P4 vs 3.2 ng/mL for intravaginal P4 at 2 months, P=0.19). Serum estradiol
      concentrations were significantly lower after oral P4 than after intravaginal P4
      (P<0.05 for all time points). Oral P4 resulted in significantly decreased body
      weight (-2.5%) compared with intravaginal P4 (+3.6%) (P=0.0001). Markers of
      breast proliferation, sex steroid receptor expression, and endometrial area did
      not differ significantly between oral P4 and intravaginal P4 treatments (P>0.1
      for all). CONCLUSIONS: Despite different pharmacodynamic profiles, oral and
      intravaginal P4 had similar effects on biomarkers in the postmenopausal breast.

PMID- 17224856
TI  - Preferential prescribing of tibolone and combined estrogen plus progestogen
      therapy in postmenopausal women.
AB  - OBJECTIVE: To verify whether tibolone is preferentially prescribed to women at an
      increased risk for endometrial and breast cancer compared with women who were
      prescribed combined estrogen + progestogen therapies, including sequential
      conjugated equine estrogens/norgestrel, sequential conjugated equine
      estrogens/medroxyprogesterone acetate, continuous conjugated equine
      estrogens/medroxyprogesterone acetate, or continuous 17beta
      estradiol/norethisterone acetate. DESIGN: This was a descriptive study using the
      General Practice Research Database, a UK primary care database. A total of 16,746
      women who, between July 1, 1999, and June 30, 2001, were prescribed either
      tibolone or one of the estrogen + progestogen regimens listed above were
      included. The main outcome measures were risk factors associated with endometrial
      cancer and breast cancer. RESULTS: The clinical background of women who were
      prescribed tibolone differed from that of women who were prescribed combination
      products. More frequently than expected, women who were most recently prescribed
      tibolone had a history of chronic breast disease, a personal history of breast
      cancer, or a history of (long-term) estrogen-only therapy. Furthermore, medical
      records of this group of women showed more frequent reports of hypertension and
      previous uterine procedures. CONCLUSION: This study confirms previous findings
      that in the United Kingdom, general practitioners seem to prescribe tibolone
      preferentially to women with increased risks of breast and endometrial cancer as
      compared with women who are prescribed estrogen + progestogen products.

PMID- 17224857
TI  - Randomized, placebo-controlled trial of the effects of drospirenone-estradiol on
      blood pressure and potassium balance in hypertensive postmenopausal women
      receiving hydrochlorothiazide.
AB  - OBJECTIVE: Drospirenone (DRSP), a spironolactone analog with aldosterone
      antagonist activity, is a novel progestogen developed for use as hormone therapy
      in postmenopausal women in combination with 17beta-estradiol (E2). DRSP/E2 lowers
      blood pressure when used alone in hypertensive postmenopausal women or when
      administered concomitantly with angiotensin-converting enzyme inhibitors or
      angiotensin receptor blockers. DRSP/E2 has not been studied in combination with
      the widely prescribed hydrochlorothiazide (HCTZ). We investigated the effects of
      3 mg DRSP/1 mg E2 versus placebo on blood pressure and potassium balance when
      added to existing therapy with 25 mg HCTZ in postmenopausal women with
      established stage I hypertension. DESIGN: This was a single-center, double-blind,
      randomized, placebo-controlled, two-treatment, two 4-week treatment period
      crossover study in 36 postmenopausal women with stage I hypertension maintained
      on 25 mg HCTZ. The endpoint was a change from baseline in systolic and diastolic
      blood pressures by 24-hour ambulatory blood pressure monitoring. Safety
      monitoring included serum potassium (mEq/L) and adverse events. RESULTS: Mean
      systolic and diastolic blood pressures by 24-hour ambulatory blood pressure
      monitoring were reduced significantly, by -7.2 and -4.5 mm Hg, respectively, with
      DRSP/E2 as compared with placebo. The decrease in potassium with HCTZ was 0.2
      mEq/L less with DRSP/E2 than placebo, suggesting a potassium-sparing effect. The
      most frequently observed adverse events with DRSP/E2 were vaginal bleeding and
      breast tenderness, which were attributable to the hormone therapy. CONCLUSIONS:
      DRSP/E2 substantially lowers systolic and diastolic blood pressure when added to
      existing antihypertensive therapy with HCTZ in hypertensive postmenopausal women.
      In addition, DRSP/E2 has a potassium-sparing effect that counteracts HCTZ-induced
      potassium loss.

PMID- 17224859
TI  - Effect of ultra-low-dose transdermal estradiol on breast density in
      postmenopausal women.
AB  - OBJECTIVE: Women with higher mammographic breast density have increased risk for
      breast cancer, and there is some evidence that a change in breast density may be
      a marker for change in risk for breast cancer. The purpose of this study was to
      determine whether 2 years of treatment with ultra-low-dose transdermal estradiol
      results in a change in breast density. DESIGN: The Ultra-Low-dose Transdermal
      Estradiol Assessment was a randomized, blinded, placebo-controlled trial of 2
      years of treatment with unopposed ultra-low-dose (0.014 mg/d) transdermal
      estradiol for prevention of osteoporosis in 417 postmenopausal women with no
      history of breast cancer who had not had a hysterectomy. We obtained mammograms
      at baseline and after 1 and 2 years of treatment from 276 of the participants.
      Right craniocaudal views were analyzed at a central radiology facility by a
      trained clinician blinded to treatment group and order of acquisition. Contour
      analysis was performed to define dense areas versus fatty tissue. Between-group
      differences in mean change in percent breast density from baseline to 1 and to 2
      years of follow-up were assessed using linear regression models adjusted for
      clinical site. RESULTS: Participants were 66 +/- 5 years old and 94% were white.
      The average percent breast density at baseline was 34%. There was no significant
      difference between treatment groups in change in percent breast density after 1
      year (between-group difference, 0.1%; 95% confidence interval, -1.3% to 1.6%) or
      2 years of treatment (0.8%; -0.6% to 2.1%). CONCLUSIONS: Two years of treatment
      with ultra-low-dose transdermal estradiol did not increase breast density.

PMID- 17224858
TI  - Efficacy of citalopram on climacteric symptoms.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of citalopram for
      climacteric symptoms and to assess the combined effect of citalopram and hormone
      therapy (HT) on climacteric symptoms in women inadequately responsive to HT
      alone. DESIGN: The study included 100 postmenopausal women who were allocated
      into one of four groups: (1) citalopram, (2) placebo, (3) citalopram+HT, or (4)
      placebo+HT. The women who were unable or unwilling to take HT were randomly
      placed in groups 1 and 2. The women who were inadequately responsive to HT were
      randomly placed in groups 3 and 4. The initial dose of citalopram was 10 mg/day
      in groups 1 and 3. After 1 week, the dose was increased to 20 mg/day. After
      starting the medication, follow-up visits took place during the fourth and eighth
      weeks of treatment. During the first and eighth weeks, women completed two
      questionnaires: a modified Kupperman index and the Menopause-Specific Quality of
      Life Questionnaire. RESULTS: Mean hot flash scores significantly improved in all
      groups (P<0.05). The reduction rates were 37% in group 1, 13% in group 2, 50% in
      group 3, and 14% in group 4. Psychosocial complaints and mean values on the
      Kupperman index significantly decreased in all groups (P<0.05). Physical well
      being significantly improved in groups 1, 3, and 4 (P<0.05). The decrease in all
      scores was significantly greater in groups 1 and 3 compared to groups 2 and 4
      (P<0.01). CONCLUSION: Citalopram is an effective alternative treatment option for
      patients who do not want to take HT for the alleviation of climacteric symptoms.
      Adjuvant treatment with a selective serotonin reuptake inhibitor increases the
      effectiveness of HT for the treatment of climacteric symptoms in women who had
      responded inadequately to HT.

PMID- 17224861
TI  - Hot flashes: what are women's expectations from therapeutic options?

PMID- 17224860
TI  - Effect of isolated isoflavone supplementation on ABCA1-dependent cholesterol
      efflux potential in postmenopausal women.
AB  - OBJECTIVE: Isoflavones may display beneficial health effects in postmenopausal
      women. We studied in a clinical trial whether isolated isoflavone treatment in
      postmenopausal women could affect reverse cholesterol transport as evaluated by
      adenosine triphosphate-binding cassette A1- (ABCA1), dependent cholesterol efflux
      from macrophages. In addition, various serum lipid and lipoprotein parameters
      were investigated. Furthermore, we separately assessed equol-producing and non
      equol-producing women. DESIGN: Postmenopausal women (n=56) were treated with
      either isoflavone or placebo tablets for 3 months in a crossover design,
      separated by a 2-month washout period. Fifteen women were classified as equol
      producers, and 15 women were classified as non-equol producers. Serum samples
      were collected before and after each treatment period. [H]-Cholesterol-labeled
      J774 macrophage cells, with and without ABCA1 up-regulation, were incubated with
      the samples, and ABCA1-dependent cholesterol efflux and serum lipid and
      lipoprotein levels were assessed. RESULTS: Serum promoted 3.1%+/-1.1% and 3.2%+/
      1.1% cholesterol efflux from macrophages after isoflavone and placebo treatment,
      respectively. Thus, isoflavone supplementation did not affect ABCA1-dependent
      cholesterol efflux to serum. However, as a novel finding, isoflavone treatment
      increased a subclass of high-density lipoprotein, the pre-beta high-density
      lipoprotein levels by 18% without affecting any other serum lipid concentrations.
      ABCA1-facilitated cholesterol efflux and lipid parameters did not differ between
      equol-producing and non-equol-producing women. CONCLUSION: In postmenopausal
      women, isolated isoflavone treatment does not affect ABCA1-dependent cholesterol
      efflux potential from macrophages but increases circulating pre-beta high-density
      lipoprotein level, which could provide beneficial vascular effects.

PMID- 17224862
TI  - Contrast-Induced Nephropathy (CIN) Consensus Working Panel: executive summary.
AB  - With the advances made in radiology and cardiology, greater numbers of patients
      are expected to undergo exposure to iodinated contrast media in the years to
      come. Contrast-induced nephropathy (CIN) accounts for a significant number of
      cases of hospital-acquired renal failure, with adverse effects on prognosis and
      healthcare costs. The CIN Consensus Working Panel is an international
      multidisciplinary group convened to address the challenges of CIN. The group
      reviewed 865 published papers, chosen for potential relevance from a
      comprehensive literature search that identified over 4000 references. The results
      were used to compile reviews covering the epidemiology and pathogenesis of CIN,
      baseline renal function measurement, risk assessment, identification of high-risk
      patients, contrast medium use, and preventive strategies. In this executive
      summary, consensus statements and an algorithm for the risk stratification and
      management of CIN are presented.

PMID- 17224863
TI  - Screening CT-coronary angiography: ready for prime time?
AB  - Computed tomographic coronary angiography (CTCA) can assist with the diagnosis of
      a variety of cardiovascular disorders. The rationale for performing screening
      CTCA is to define the presence, absence, and severity of coronary artery disease,
      particularly in those patients who are categorized to be at intermediate risk by
      conventional risk factor assessment for a cardiovascular event. In addition to
      coronary artery disease, the interventional cardiologist can also use CTCA to
      evaluate the presence of an anomalous origin of the coronary arteries, the size
      of the coronary arteries for potential stent placement, the extent of coronary
      calcium in the obstructive segment and bypass graft patency. With conventional
      coronary angiography, the combined radiogenic and non-radiogenic mortality is
      0.13%, compared to 0.07% with CTCA. Radiation to the clinician is also greatly
      reduced.

PMID- 17224864
TI  - A systematic overview of anomalous coronary anatomy and an examination of the
      association with sudden cardiac death.
AB  - Coronary artery anomalies are a frequently neglected topic in cardiology.
      However, they are an important cause of cardiac ischemia and sudden death.
      Anomalous pulmonary artery and anomalous aortic origins of the coronaries are 2
      major types of coronary artery anomalies. This article will examine the
      occurrence of these anomalies in the absence of associated congenital defects. A
      review of the literature reveals that the anomaly most commonly associated with
      sudden death is a left main coronary artery arising from the right aortic sinus
      of Valsalva with an interarterial course. The increased risk of sudden death with
      this anomaly has been associated with any of 4 high-risk features: slit-like
      ostium, acute-angle take-off, intramural aortic segment, and interarterial
      course.

PMID- 17224865
TI  - Therapeutic goals for effective platelet inhibition: a consensus document.
AB  - Clopidogrel combined with aspirin is the mainstay of antiplatelet therapy for
      patients who present with acute coronary syndromes as well as following either
      bare metal or drug-eluting stent placement. Limitations of clopidogrel therapy
      include the relatively long time course required to achieve maximal inhibition of
      platelet aggregation, individual variability in response to its effect, the risk
      of bleeding during its administration, and the irreversible nature of P2Y12
      receptor binding, which leads to a prolonged time course for recovery of platelet
      function following discontinuation of clopidogrel. Several investigational P2Y12
      receptor antagonists have pharmacological properties that may overcome some or
      all of these limitations. These novel agents such as prasugrel, AZD6140, and
      cangrelor are in advanced stages of clinical development for potential use in
      patients with coronary artery disease.

PMID- 17224867
TI  - Constrictive pericarditis after coronary artery bypass.
AB  - A 67-year-old male patient received a coronary artery bypass graft. Less than 2
      months afterward, he presented with recurrent exacerbations of congestive heart
      failure. His response to a standard treatment regimen for heart failure was
      partly successful, but a few days after discharge he was readmitted for worsening
      dyspnea and edema. Doppler echocardiography suggested the hemodynamics of
      constrictive pericarditis. Magnetic resonance imaging showed thickened
      pericardium with exudates in the pericardial space. Cardiac catheterization
      confirmed the diagnosis, showing equalization of diastolic pressures of the left
      and right ventricles. The patient underwent subtotal pericardiectomy with
      resolution of the pericardial disease, but he died from respiratory
      insufficiency.

PMID- 17224868
TI  - Antiphospholipid antibody syndrome and acute stent thrombosis.
AB  - Antiphospholipid antibody syndrome is an autoimmune disease characterized by the
      presence of antiphospholipid antibodies and at least 1 clinical manifestation,
      most commonly vascular thrombosis or fetal loss. Antiphospholipid antibodies are
      associated with multiple cardiac manifestations, including valve problems,
      thrombosis within cardiac chambers, and coronary artery thrombosis. We describe
      the case of a 46-year-old woman with recurrent coronary stent thrombosis who was
      found to have antiphospholipid antibodies. After successful coronary artery
      bypass graft surgery, the patient was kept on twice-daily injections of the low
      molecular-weight heparin enoxaparin and started on warfarin. Six days after
      surgery, she was discharged from the hospital in stable condition.

PMID- 17224869
TI  - Heart failure with preserved ejection fraction: disturbing trends.

PMID- 17224870
TI  - Lowering levels of lipids and homocysteine.

PMID- 17224871
TI  - Diabetes, hyperglycemia, and the cardiologist: a call to action for optimizing
      care. Introduction.

PMID- 17224872
TI  - Management of diabetes in the hospital.
AB  - Hyperglycemia is a common complication in hospitalized patients, particularly
      among patients with acute myocardial infarction. It is an independent predictor
      of cardiovascular mortality and morbidity. Management of hyperglycemia with
      intensive insulin therapy has been shown to improve survival, reduce length of
      stay in intensive care, and decrease complications such as renal failure or
      prolonged mechanical ventilation in critically ill patients. Insulin infusions
      are now recommended for the treatment of hyperglycemia in several groups of
      patients, including patients in the intensive care unit and those undergoing
      major surgery. Implementation of protocols and standard orders may be useful to
      ensure the optimal use of insulin in the management of hyperglycemia. Fewer data
      are available to guide the management of hyperglycemia outside the intensive care
      setting. A variety of subcutaneous insulin regimens are now available with
      different pharmacokinetic profiles. These agents are preferred to controlling
      blood sugar with sliding scale regimens alone. Oral therapies may also have a
      role, but many agents may be contraindicated in the acute setting. As
      hyperglycemia has been shown to have significant adverse impact on patient
      outcomes in a variety of settings, cardiologists need to play a role in efforts
      to achieve adequate glycemic control in hospitalized patients with hyperglycemia
      in an effort to improve patient outcomes.

PMID- 17224873
TI  - Prevalence of newly diagnosed diabetes in clinical settings.
AB  - A substantial number of patients being evaluated or treated for cardiovascular
      disease are found to have glucometabolic disorders. Identification of such
      patients is important because treatment for coronary artery disease and stroke
      needs to be individualized. Hyperglycemia on admission or during hospitalization
      regardless of whether diabetes mellitus is known to exist in these patients is
      associated with increased morbidity and mortality. Despite the fact that this has
      been known for some time, various strategies to reduce hyperglycemia have had
      mixed results in cardiac outcomes. Another important factor is that a new
      diagnosis of diabetes mellitus in these patients should result in the patient's
      triage to appropriate healthcare professionals to optimize glycemic control. The
      prevalence of hyperglycemia in patients admitted with acute cardiovascular
      disease and the effect of hyperglycemia on outcome are reviewed.

PMID- 17224874
TI  - Anti-inflammatory effects of insulin and pro-inflammatory effects of glucose:
      relevance to the management of acute myocardial infarction and other acute
      coronary syndromes.
AB  - Hyperglycemia worsens morbidity and mortality for patients in intensive care or
      with acute myocardial infarction, stroke, or coronary artery bypass grafts. The
      control of hyperglycemia with insulin improves clinical outcomes for patients
      with these conditions. This article reviews the anti-inflammatory effects of
      insulin and pro-inflammatory effects of glucose and free fatty acids, and
      provides a mechanistic justification for maintaining euglycemia with insulin
      infusions. Hyperglycemia induced by infusions of a fixed dose of insulin with
      high rates of glucose may neutralize the benefit of insulin, and such regimens
      should be replaced by infusion of insulin to restore and maintain euglycemia.

PMID- 17224875
TI  - From hyperglycemia to the risk of cardiovascular disease.
AB  - Blood glucose is a continuous, progressive risk factor for cardiovascular disease
      (CVD) throughout the dysglycemic range. There is also evidence that post-prandial
      hyperglycemia may be a better predictor of CVD risk than fasting plasma glucose
      or A1C. Targeting normoglycemia appears to reduce CVD events in diabetes mellitus
      (DM), although definitive studies in type 2 DM, as well as in prediabetes, are
      ongoing. Prediabetes has some, but not total, overlaps with the metabolic
      syndrome. Patients with the metabolic syndrome are at a significantly increased
      risk for both CVD and DM. Although the individual components of the syndrome
      predict risk for CVD to approximately equal degree, increased blood glucose,
      perhaps not surprisingly, is the best predictor of diabetes. Finally, there are
      multiple mechanisms by which hyperglycemia can increase the risk for CVD.

PMID- 17224876
TI  - Mechanism by which hyperglycemia plays a role in the setting of acute
      cardiovascular illness.
AB  - Acute hyperglycemia is associated with excess morbidity and mortality in acute
      cardiovascular illness in both diabetic and nondiabetic patients. Hyperglycemia
      is associated with altered myocardial energetics, but abnormalities in glucose
      oxidation and glycolysis do not fully account for this excess risk. Hyperglycemia
      leads to a pro-oxidative/proinflammatory state that is associated with
      endothelial dysfunction, diminished coronary vasodilatory reserve, and a
      prothrombotic state. Hyperglycemia negates the protective effect of ischemic
      preconditioning and, most importantly, appears to interfere with the salutary
      effects of insulin in acute cardiovascular illness. Aggressive therapy with
      continuous infusion of insulin seems to improve a host of metabolic and
      physiologic effects associated with acute hyperglycemia and appears warranted if
      euglycemia can be maintained.

PMID- 17224877
TI  - Glucose, insulin, and potassium for metabolic support in acute myocardial
      infarction: is the jury still out?
AB  - During ischemic and cardiomyopathic conditions, carbohydrate (glucose) metabolism
      in cardiomyocytes predominates over use of free fatty acids. The shift to glucose
      metabolism is a physiologic response to ischemia, which in many patients,
      particularly diabetics or those who are insulin-resistant, is blunted. Free fatty
      acid metabolism during ischemia produces higher levels of lactate and hydrogen
      ions within the ischemic cells. This in turn degrades myocardial contractility,
      induces diastolic dysfunction, and reduces the arrhythmogenic threshold of the
      cardiomyocyte. Suppression of free fatty acid uptake and oxidation by any means
      will increase myocardial glucose substrate utilization in ischemia.
      Theoretically, then, an insulin-glucose solution that can augment GLUT-1 and GLUT
      4 translocation to the sarcolemmal membrane can assist cardiomyocyte survival
      during ischemia; however, study results have not supported metabolic therapy. It
      is essential for any investigation of glucose, insulin, potassium therapy to
      separate out the effect of hyperglycemia and glucose toxicity to make any
      meaningful comment on the effectiveness of metabolic support in myocardial
      infarction.

PMID- 17224878
TI  - Anticoagulation in the cath lab: a contemporary approach. Introduction.

PMID- 17224879
TI  - Bleeding as a predictor of mortality risk.
AB  - The increased rate of bleeding during and after cardiac procedures is a concern.
      The best strategy is prevention of bleeding complications with anticoagulant
      therapy that provides an adequate anti-thrombotic effect while reducing bleeding.
      The independent relationship between bleeding and blood transfusion and mortality
      among patients with coronary artery disease is reviewed. Findings suggest that in
      the modern era of percutaneous coronary intervention, prevention of bleeding
      should be a goal of therapy, which can be achieved while preserving the low rate
      of ischemic complications.

PMID- 17224880
TI  - Practical guidelines for the use of anticoagulants in the catheterization
      laboratory.
AB  - Optimal treatment of patients during percutaneous coronary interventions (PCIs)
      is constantly changing as clinical trials provide new and clinically relevant
      information. Clinicians need to be aware of this information to incorporate these
      new strategies into clinical practice, leading to improvements in the care of
      patients. The direct thrombin inhibitor, bivalirudin, will play an increasingly
      important role as the primary anticoagulant for PCIs because it meets the
      criteria as a safer, cost-effective, and convenient agent in a spectrum of
      clinical scenarios. This article will provide practical guidelines to assist the
      interventional cardiologist to prepare his or her patient for PCI and will focus
      on some of the more common and more difficult patient cohorts, in particular
      those patients with chronic kidney disease as well as the elderly, 2 of the
      fastest growing groups of patients undergoing PCI.

PMID- 17224881
TI  - Bivalirudin in acute coronary syndromes and percutaneous coronary intervention.
AB  - The standard of care for patients with acute coronary syndrome is antithrombotic
      and antiplatelet therapies along with early percutaneous coronary intervention.
      Because of the limitations of heparin, there has been an interest in direct
      thrombin inhibitors, such as bivalirudin, which is now the anticoagulant of
      choice in percutaneous coronary intervention.

PMID- 17224882
TI  - Platelet protagonist/antagonist: understanding the distinguishing characteristics
      of anticoagulants.
AB  - Clinical coagulation laboratory tests do not accurately reflect hemostasis and
      thrombosis in vivo. Thrombin generation in vivo occurs in 3 overlapping phases:
      initiation, priming, and propagation. During initiation, injury to the vessel
      wall exposes the cells to tissue factors, which lead to the production of small
      amounts of thrombin. During priming, the thrombin that is generated initially
      binds to platelets and activates them through protease-activated receptors.
      During the propagation phase, factor X is activated by the factor IXa/VIIIa
      complex that is assembled on the activated platelet surface. Subsequent formation
      of factor Xa/Va complexes on the platelet surface leads to a burst of thrombin
      and fibrin formation. Pharmacologic concentrations of a direct thrombin
      inhibitor, bivalirudin, inhibit thrombin-induced activation of platelets to a
      greater extent than pharmacologic concentrations of unfractionated heparin.

PMID- 17224885
TI  - Contemporary issues in the cath lab. Introduction.

PMID- 17224883
TI  - Economic implications of bivalirudin in the cardiac catheterization laboratory.
AB  - More than 1.2 million percutaneous coronary intervention (PCI) procedures are
      performed each year in the United States, with average hospital costs of more
      than $10,000 per procedure. Despite ongoing improvements in device technology and
      adjunct pharmacology, both ischemic complications (eg, periprocedural myocardial
      infarction) and bleeding complications remain relatively common and are
      associated with both increased costs (in the short term) and mortality (in the
      longer term). Recently, the Randomized Evaluation of PCI Linking Angiomax to
      Reduced Clinical Events (REPLACE)-2 clinical trial demonstrated that the use of
      the direct thrombin inhibitor, bivalirudin, with provisional glycoprotein (GP)
      IIb/IIIa inhibitor for selected patients in place of a conventional
      anticoagulation strategy of heparin and routine use of a GP IIb/IIIa inhibitor,
      resulted in comparable rates of ischemic complications and a significant
      reduction in the frequency of both major and minor bleeding complications. A
      prospectively designed economic analysis was performed using data from 4651 US
      patients who participated in REPLACE-2. In this analysis, patients who were
      assigned to the bivalirudin and provisional GP IIb/IIIa inhibitor strategy had
      anticoagulation costs during PCI that were approximately $400 per patient lower
      than those with heparin plus routine GP IIb/IIIa inhibition. Bivalirudin also
      produced corresponding decreases in total in-hospital costs and aggregate 30-day
      medical care costs. These cost savings derived both from the lower acquisition
      cost of the antithrombotic therapy and the reduced rate of bleeding
      complications, which accounted for approximately 20% of the cost offsets. These
      results suggest that for patients similar to those studied in REPLACE-2 (ie, low
      to moderate risk PCI procedures), use of bivalirudin and provisional GP IIb/IIIa
      inhibition compared with heparin and routine GP IIb/IIIa inhibition can result in
      similar rates of ischemic complications, reduced bleeding, and substantial cost
      savings to both hospitals and the healthcare system. Whether these benefits can
      be extended to higher risk patient subsets including patients with non-ST
      elevation or ST elevation myocardial infarction is currently under investigation.

PMID- 17224886
TI  - Optimizing antiplatelet therapy for the ACS patient: reacting to clinical trial
      data from the ISAR-REACT-2 studies.
AB  - Antiplatelet therapy is the cornerstone of treatment for patients with an acute
      coronary syndrome (ACS). However, patients presenting with possible ACS are a
      heterogeneous population, and there is a choice of many potential combination
      antiplatelet therapies, with aspirin, thienopyridines (eg, clopidogrel), and
      glycoprotein (GP) IIb/IIIa antagonists. The ISAR-REACT-2 trial investigated the
      optimal application of triple (aspirin 1 thienopyridine 1 GP IIb/IIIa inhibitor)
      versus dual (aspirin 1 thienopyridine) antiplatelet therapy for patients with ACS
      undergoing percutaneous coronary intervention. Abciximab was associated with a
      significant 25% relative reduction in risk for the 30-day combined endpoint of
      death, myocardial infarction, or urgent target vessel revascularization. All of
      this benefit was confined to the patients with elevated troponin levels. The data
      indicate that troponin can be used as a biomarker to identify patients most
      likely to benefit from the addition of a GP IIb/IIIa antagonist.

PMID- 17224887
TI  - The relationship of platelet reactivity to the occurrence of post-stenting
      ischemic events: emergence of a new cardiovascular risk factor.
AB  - The reactivity of platelets to agonists plays a central role in the genesis of
      thrombosis following percutaneous coronary intervention (PCI) and spontaneous
      plaque rupture. Antiplatelet therapy has reduced the occurrence of thrombotic
      events following PCI, including myocardial infarction and stent thrombosis.
      Because the platelet is a fundamental component in the generation of an arterial
      thrombus and the stimulus for thrombosis is marked in PCI, it is logical to
      predict that patients with superior platelet inhibition would have the best
      outcomes with respect to ischemic events post PCI. However, until recently there
      was little information linking measurements of high ex vivo platelet reactivity
      to the occurrence of ischemic events. An emerging body of data, mostly from small
      studies, supports the pivotal link between periprocedural platelet physiology and
      increased risk of adverse thrombotic events. This review explores the available
      information linking platelet reactivity during and after PCI to the occurrence of
      adverse events, including myocardial infarction, recurrent ischemia within 6
      months, and stent thrombosis.

PMID- 17224888
TI  - Evolving antithrombotic treatment strategies for acute ST-elevation myocardial
      infarction.
AB  - The importance of the dissolution and prevention of thrombosis in treating
      patients with ST-segment elevation myocardial infarction (STEMI) has motivated
      the development of novel therapies targeting platelet aggregation and thrombus
      formation. In contemporary practice, the current challenge is the integration of
      these therapies into reperfusion strategies that may include fibrinolytic therapy
      or percutaneous coronary revascularization (PCI). Evidence from clinical trials
      shows that addition of glycoprotein IIb/IIIa inhibition to PCI for treatment of
      STEMI has substantially lowered the incidence of recurrent ischemic events and
      improved early survival. In contrast, current trials evaluating a strategy termed
      facilitated PCI, or planned early PCI after pharmacologic reperfusion therapy,
      have presently demonstrated an increased risk of bleeding events and mortality.
      Additional trials have extended the role of antithrombotic agents to STEMI that
      previously were reserved for patients undergoing elective revascularization or
      among those treated with non-ST-segment elevation acute coronary syndromes. For
      example, the recent studies have demonstrated the benefit of clopidogrel
      treatment among STEMI patients treated with fibrinolysis in reducing the
      incidence of infarct artery reocclusion and improving early survival. Other
      anticoagulants under investigation in the management of STEMI include enoxaparin,
      bivalirudin, and fondaparinux. This review summarizes the current status of
      pharmacologic and invasive strategies for the treatment of STEMI and describes
      recent and ongoing directions for clinical investigation.

PMID- 17224889
TI  - Effects of GP IIb/IIIa inhibitors on vascular inflammation, coronary
      microcirculation, and platelet function.
AB  - The platelet glycoprotein (GP) IIb/IIIa inhibitors differ markedly in their
      pharmacokinetics, pharmacodynamics, and differential receptor affinities.
      Abciximab and the small-molecule GP IIb/IIIa inhibitors (eptifibatide, tirofiban)
      have separate, distinct binding sites on the GP IIb/IIIa receptor complex. The
      affinity of abciximab for the platelet GP IIb/IIIa integrin receptor, together
      with non-platelet-receptor mediated effects achieved through its affinity for the
      aVb3 and CD11b/18 receptors, most likely contribute to the clinical benefit
      associated with the use of abciximab as adjunctive pharmacotherapy during primary
      percutaneous coronary intervention for the treatment of ST-elevation acute
      myocardial infarction.

PMID- 17224890
TI  - Impact of chronic kidney disease and diabetes on percutaneous coronary
      intervention outcomes.
AB  - Abnormalities of glucose metabolism and chronic kidney disease (CKD) complicate
      treatment and outcomes for patients undergoing percutaneous coronary intervention
      (PCI). Likely causes of the complicating effects of diabetes include
      hyperglycemia, abnormalities of microvascular perfusion, and a prothrombotic and
      proinflammatory state. CKD predisposes to atherosclerosis, adds to the mortality
      and morbidity risk of cardiovascular disease (CVD), and increases risks for
      patients undergoing PCI. The complexity of the renal dysmetabolic syndrome and
      its close association with CVD must be taken into account when developing a
      therapeutic plan for these patients. Clinical data support the use of abciximab
      for patients with disturbances of glucose metabolism or with CKD who are
      undergoing PCI. The use of drug-eluting stents reduces the rate of target vessel
      revascularization and restenosis.

PMID- 17224891
TI  - Accelerating time to reperfusion in acute myocardial infarction: prehospital and
      emergency department strategies, systems of care, and pharmacologic
      interventions.
AB  - Although primary percutaneous coronary intervention has emerged as the preferred
      reperfusion strategy for patients with ST-segment elevation myocardial infarction
      (STEMI), it is available only in a minority of US hospitals. The fundamental
      problem is that there is presently no organized, uniform, national STEMI triage
      and treatment system that is comparable to the well-developed, highly successful
      system in the United States that directs major trauma victims to verified trauma
      centers. This article reviews prehospital and emergency department triage
      strategies, systems, and pharmacologic interventions for patients with STEMI that
      can help shorten the time to reperfusion in these patients.

PMID- 17224892
TI  - The expanding role of endoscopic ultrasound in pancreatic disease.
AB  - Since endoscopic ultrasound (EUS) was first developed in the 1980s, this
      technology has emerged as the principal modality for imaging the pancreas. When
      compared with other imaging techniques, EUS can more accurately image solid
      lesions of the pancreas and determine vascular involvement that might preclude
      surgery. Furthermore, EUS-guided fine needle aspiration allows safe and accurate
      sampling and histological diagnosis of these lesions. EUS also plays a large role
      in the evaluation of cystic lesions of the pancreas. EUS cyst morphology, as well
      as fluid analysis obtained by fine needle aspiration, can often be used to
      diagnose the etiology of these lesions, helping the clinician to more accurately
      assess the presence or potential for malignancy. EUS can also predict the
      probability of the presence of chronic pancreatitis, primarily on the basis of
      histological correlates. The focus of this review is to discuss the role of EUS
      in these and other commonly encountered pancreatic diseases.

PMID- 17224893
TI  - Chromoendoscopy and its alternatives for colonoscopy: useful in the United
      States?
AB  - American endoscopists have essentially ignored chromoendoscopy (dye spraying) in
      the colon and overwhelmingly perform white-light colonoscopy only. The published
      studies suggest that routine use of chromoendoscopy in Western populations will
      lead to identification of additional flat lesions. However, a number of these
      studies have design flaws. The authors' interpretation of the existing data is
      that pancolonic chromoendoscopy to detect flat and depressed lesions is not yet
      proven as a useful and therefore necessary adjunct to routine colonoscopic
      examination in non-inflammatory bowel disease patients in the United States.
      Chromoendoscopy, particularly combined with magnification, is very effective in
      delineating the pit pattern of polyps and in allowing real-time differentiation
      of adenomatous from non-adenomatous lesions. There might be a role for chromo
      endoscopy with high magnification in the delineation of unresected portions of
      lateral spreading tumors being removed by piecemeal polypectomy and in the
      evaluation of polypectomy scars during endoscopic follow-up. The authors suggest
      that US endoscopists begin to familiarize themselves with shape classification,
      and that they learn a method to determine histology in real time.

PMID- 17224894
TI  - The prevention of gastropathy and upper abdominal symptoms caused by nonsteroidal
      anti-inflammatory drugs.
AB  - The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is increasing, primarily
      due to arthritis in the aging population. This article reviews current data on
      the risk of gastrointestinal complications related to NSAIDs and strategies to
      manage risk in patients taking these agents. Risks of NSAID use include
      gastrointestinal ulceration, hemorrhage, or perforation; renal dysfunction;
      death; and dyspepsia. Alternate therapies include use of non-NSAID analgesics;
      low-dose NSAIDs; and concurrent administration of cytoprotective agents with
      NSAIDs, acid inhibitors, proton pump inhibitors, and COX-2 agents.

PMID- 17224895
TI  - Rifaximin for small intestinal bacterial overgrowth: reviewing the evidence.

PMID- 17224896
TI  - Clostridium difficile: What to do? Less responsive to treatment, more relapses.

PMID- 17224897
TI  - Eosinophilic esophagitis in adults: clinical, endoscopic, and histologic
      findings, and response to treatment with fluticasone propionate.

PMID- 17224898
TI  - Malformations of cortical development and epilepsy, part 1: diagnosis and
      classification scheme.
AB  - Malformations of cortical development (MCDs) are a common cause of epilepsy,
      although seizures are not always the most prominent neurologic manifestation of
      these disorders. In localization-related epilepsy, certain features should create
      a strong suspicion that an MCD is the underlying cause; these include
      developmental delay and static focal neurologic deficits, a family history of
      developmental delay or epilepsy, frequent seizures from onset, and episodes of
      focal status epilepticus. MCDs can be classified according to a number of
      different criteria emphasizing clinical phenotype, imaging findings, pathology,
      or genetic defects. The overall classification of MCDs is based on the 3
      fundamental events of cortical formation: 1) proliferation of neurons and glia in
      the ventricular and subventricular zones; 2) multidirectional migration of
      immature but postmitotic neurons to the developing cerebral cortex; and 3)
      cortical organization. Among the most common and distinct syndromes and entities
      affecting patients with MCDs and epilepsy are focal cortical dysplasia,
      hemimegalencephaly, tuberous sclerosis, classical lissencephaly, periventricular
      nodular heterotopia, focal subcortical heterotopia, polymicrogyria, and
      schizencephaly, all of which are discussed herein.

PMID- 17224899
TI  - Surgery for intracerebral hematoma: the search for the elusive right candidate.
AB  - The value of surgery for patients with intracerebral hemorrhage (ICH) remains a
      topic of debate. Although several studies have been unable to prove the benefit
      of surgical intervention of ICH, there is available evidence to suggest that some
      patients may experience favorable outcome with surgery. Identifying optimal
      candidates and the timing of surgery for the treatment of ICH are crucial issues.
      Studies have explored the value of early and ultra-early surgical intervention,
      as well as the role of stereotactic hematoma evacuation. The International
      Surgical Trial in Intracerebral Hemorrhage suggested that favorable surgical
      outcome was more likely for patients with superficial hematomas, and patients who
      underwent craniotomy in the trial seemed to fare better than those treated with
      other surgical techniques. A retrospective study of patients with brain tissue
      shift has provided evidence that surgery may benefit some deteriorating patients;
      treatment decisions in this patient population should be based on case-by-case
      assessments of the likelihood of recovery after evacuation. It is critical that
      therapeutic alternatives for patients with ICH continue to be explored.

PMID- 17224900
TI  - Neurologic complications of primary systemic amyloidosis.
AB  - Amyloid is a botanical term that denotes a waxy, amorphous, eosinophilic material
      and is used to describe similar pathological findings in humans. The deposits in
      primary systemic amyloidosis are derived from monoclonal serum proteins in plasma
      cell dyscrasia, which are degraded locally in tissues and deposited in insoluble
      sheets that damage organs. The cause of organ damage in amyloidosis is unclear
      but most likely due to the direct toxic effects of amyloid. Symptoms of the
      disorder include neuropathy, myopathy, and cardiac or renal insufficiency; there
      is often multiple-organ involvement. Congestive heart failure and nephrotic
      syndrome are predominant causes of death. Differential difficulties exist in
      diagnosing the disorder, and familial amyloid polyneuropathy directly mimics the
      disease. Diagnostic tools include electromyography, laboratory testing for
      abnormalities in serum and urine, and histological investigation of appropriate
      tissue. The median survival of patients is 2 years. However, melphalan and
      prednisone treatment for at least 1 year has resulted in increased survival
      rates. There have also been reports of benefit from high-dose chemotherapy
      followed by peripheral blood stem cell transplantation. Without early therapy,
      however, the disease has a dismal prognosis, and peripheral neuropathy usually
      persists or worsens despite therapy and improvement in other organs.

PMID- 17224901
TI  - Botulism: the challenge of diagnosis and treatment.
AB  - Botulism is a rare paralytic disease caused by a neurotoxin produced from the
      spore-forming bacterium Clostridium botulinum and in rare cases Clostridium
      butyricum and Clostridium baratii. Botulism has 4 naturally occurring syndromes:
      foodborne, wound, infant botulism, and adult intestinal toxemia. Inhalational
      botulism could result from aerosolization of botulinum toxin, and iatrogenic
      botulism can result from injection of toxin. All of these produce the same
      clinical syndrome of symmetrical cranial nerve palsies followed by descending,
      symmetric flaccid paralysis of voluntary muscles, which may progress to
      respiratory compromise and death. Treatment includes meticulous intensive care
      that includes mechanical ventilation, when necessary, and administration of
      antitoxin.

PMID- 17224902
TI  - Seizures, cognitive abnormalities, and abnormal magnetic resonance imaging
      findings in a 19-year-old woman.
AB  - In this case scenario, the reader has the the opportunity to diagnose the patient
      described in the title, on the basis of the history, examination results,
      laboratory evaluations, and neurophysiologic and imaging findings. The diagnosis
      and a discussion of the case are presented on pages 195-197.

PMID- 17224903
TI  - Advances in the diagnosis, treatment, and understanding of Parkinson's disease
      and parkinsonism.
AB  - Highlights from the Twentieth Annual Symposium on the Etiology, Pathogenesis, and
      Treatment of Parkinson's Disease and Other Movement Disorders October 8, 2006,
      Chicago, IL. Why do substantia nigra neurons die in patients with Parkinson's
      disease? Dr. Weiner discusses an interesting hypothesis presented at the 2006
      symposium. He also reviews some of the other meeting highlights, including
      reports on pathologic gambling, the under-recognition of drug-induced
      parkinsonism, and the latest studies on estrogen replacement therapy, deep brain
      stimulation, and botulinum toxin.

PMID- 17224907
TI  - Loss of AP-2alpha results in deregulation of E-cadherin and MMP-9 and an increase
      in tumorigenicity of colon cancer cells in vivo.
AB  - Activator protein-2 (AP-2) is a transcription factor that regulates proliferation
      and differentiation in mammalian cells and has been implicated in the acquisition
      of the metastatic phenotype in several types of cancer. Herein, we examine the
      role of AP-2alpha in colon cancer progression. We provide evidence for the lack
      of AP-2alpha expression in the late stages of colon cancer cells. Re-expression
      of the AP-2alpha gene in the AP-2alpha-negative SW480 colon cancer cells
      suppressed their tumorigenicity following orthotopic injection into the cecal
      wall of nude mice. The inhibition of tumor growth could be attributed to the
      increased expression of E-cadherin and decreased expression and activity of
      matrix-metalloproteinase-9 (MMP-9) in the transfected cells, as well as a
      substantial loss of their in vitro invasive properties. Conversely, targeting
      constitutive expression of AP-2alpha in AP-2-positive KM12C colon cancer cells
      with small interfering RNA resulted in an increase in their invasive potential,
      downregulation of E-cadherin and increased expression of MMP-9. In SW480 cells,
      re-expression of AP-2alpha resulted in a fourfold increase in the activity of E
      cadherin promoter, and a 5-14-fold decrease in the activity of MMP-9 promoter,
      indicating transcriptional regulation of these genes by AP-2alpha. Chromatin
      immunoprecipitation assay showed that re-expressed AP-2alpha directly binds to
      the promoter of E-cadherin, where it has been previously reported to act as a
      transcriptional activator. Furthermore, chromatin immunoprecipitation assay
      revealed AP-2alpha binding to the MMP-9 promoter, which ensued by decreased
      binding of transcription factor Sp-1 and changes in the recruitment of
      transcription factors to a distal AP-1 element, thus, contributing to the overall
      downregulation of MMP-9 promoter activity. Collectively, our data provide
      evidence that AP-2alpha acts as a tumor suppressor gene in colon cancer..

PMID- 17224908
TI  - The ubiquitin-proteasome system regulates p53-mediated transcription at p21waf1
      promoter.
AB  - The ubiquitin (Ub)-proteasome system (UPS) promotes the proteasomal degradation
      of target proteins by decorating them with Ub labels. Emerging evidence indicates
      a role of UPS in regulating gene transcription. In this study, we provided
      evidence for the involvement of UPS in the transcriptional activation function of
      tumor suppressor p53. We showed that both ubiquitylation and proteasomal
      functions are required for efficient transcription mediated by p53. Disruption of
      transcription by actinomycin D, 5,6-dichloro-1-beta-D-ribofuranosyl-benzimadazole
      or alpha-amanitin leads to accumulation of cellular p53 protein. Proteasome
      inhibition by MG132 increases the occupancy of p53 protein at p53-responsive
      p21(waf1) promoter. In addition, the Sug-1 component of 19S proteasome physically
      interacts with p53 in vitro and in vivo. Moreover, in response to ultraviolet
      induced DNA damage, both the 19S proteasomal components, Sug1 and S1, are
      recruited to p21(waf1) promoter region in a kinetic pattern similar to that of
      p53. These results suggested that UPS positively regulates p53-mediated
      transcription at p21(waf1) promoter.

PMID- 17224911
TI  - Testicular metastasis from carcinoma of prostate: report of two cases.
AB  - Despite the high incidence of prostatic adenocarcinoma and its ability for wide
      dissemination, metastatic involvement of testis is rather uncommon. We report two
      cases (aged 76 and 55 years, respectively), where unilateral testicular
      metastasis was incidentally discovered after bilateral orchiectomy following
      detection of adenocarcinoma prostate in six-quadrant trucut specimen. Both
      patients had obstructive voiding symptoms, hard nodular prostate on direct rectal
      examination and raised serum prostate-specific antigen levels, without associated
      systemic or testicular symptoms. Extensive evaluation excluded any other possible
      primary, although axial skeletal metastasis was detected on radionucleotide bone
      scans, in the first case. These cases highlight the need for proper evaluation of
      testes and para-testicular structures, for accurate staging of these tumors and
      to exclude any possible metastasis.

PMID- 17224909
TI  - Ubiquitin-independent degradation of p53 mediated by high-risk human
      papillomavirus protein E6.
AB  - In vitro, high-risk human papillomavirus E6 proteins have been shown, in
      conjunction with E6-associated protein (E6AP), to mediate ubiquitination of p53
      and its degradation by the 26S proteasome by a pathway that is thought to be
      analogous to Mdm2-mediated p53 degradation. However, differences in the
      requirements of E6/E6AP and Mdm2 to promote the degradation of p53, both in vivo
      and in vitro, suggest that these two E3 ligases may promote p53 degradation by
      distinct pathways. Using tools that disrupt ubiquitination and degradation, clear
      differences between E6- and Mdm2-mediated p53 degradation are presented. The
      consistent failure to fully protect p53 protein from E6-mediated degradation by
      disrupting the ubiquitin-degradation pathway provides the first evidence of an E6
      dependent, ubiquitin-independent, p53 degradation pathway in vivo.

PMID- 17224912
TI  - Highly elevated PSA and dietary PhIP intake in a prospective clinic-based study
      among African Americans.
AB  - African-American men die from prostate cancer (PC) nearly twice as often as white
      US men and consume about twice as much of the predominant US dietary heterocyclic
      amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a genotoxic rat
      prostate carcinogen found primarily in well-cooked chicken and beef. To
      investigate the hypothesis that PhIP exposure increases PC risk, an ongoing
      prospective clinic-based study compared PC screening outcomes with survey-based
      estimates of dietary PhIP intake among 40-70-year-old African-American men with
      no prior PC in Oakland, CA. They completed food-frequency and meat
      cooking/consumption questionnaires and had a prostate-specific antigen (PSA) test
      and digital-rectal exam. Results for 392 men indicated a 17 (+/-17) ng/kg day
      mean (+/-1 s.d.) daily intake of PhIP, about twice that of white US men of
      similar age. PhIP intake was attributable mostly to chicken (61%) and positively
      associated (R(2)=0.32, P<0.0001) with saturated fat intake. An odds ratio (95%
      confidence interval) of 31 (3.1-690) for highly elevated PSA > or =20 ng/ml was
      observed in the highest 15% vs lowest 50% of estimated daily PhIP intake (> or
      =30 vs < or =10 ng/kg day) among men 50+ years old (P=0.0002 for trend) and
      remained significant after adjustment for self-reported family history of
      (brother or father) PC, saturated fat intake and total energy intake. PSA
      measures were higher in African-American men with positive family history
      (P=0.007 all men, P<0.0001 highest PSA quartile). These preliminary results are
      consistent with a positive association between PhIP intake and highly elevated
      PSA, supporting the hypothesis that dietary intervention may help reduce PC risk.

PMID- 17224913
TI  - Overview of the pharmacogenomics of cigarette smoking.
AB  - Cigarette smoking increases the risk of numerous health problems, including
      cancer, cardiovascular and pulmonary disorders, making smoking the leading cause
      of preventable death in the world. Nicotine is primarily responsible for the
      highly addictive properties of cigarettes. Although the majority of smokers
      express a desire to quit, few are successful in doing so. Twin and family studies
      have indicated substantial genetic contributions to smoking behaviors. One major
      research focus has been to elucidate the specific genes involved; this has been
      accomplished primarily through genome-wide linkage analyses and candidate gene
      association studies. Much attention has focused on genes involved in the
      neurotransmitter pathways for the brain reward system and genes altering nicotine
      metabolism. This paper reviews the current state of knowledge for genetic factors
      implicated in smoking behaviors, and examines how genetic variations may affect
      therapeutic outcomes for drugs used to assist smoking cessation.

PMID- 17224914
TI  - Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast
      cancer.
AB  - Paclitaxel is commonly used in the treatment of breast cancer. Variability in
      paclitaxel clearance may contribute to the unpredictability of clinical outcomes.
      We assessed genomic DNA from the plasma of 93 patients with high-risk primary or
      stage IV breast cancer, who received dose-intense paclitaxel, doxorubicin and
      cyclophosphamide. Eight polymorphisms in six genes associated with metabolism and
      transport of paclitaxel were analyzed using Pyrosequencing. We found no
      association between ABCB1, ABCG2, CYP1B1, CYP3A4, CYP3A5 and CYP2C8 genotypes and
      paclitaxel clearance. However, patients homozygous for the CYP1B1*3 allele had a
      significantly longer progression-free survival than patients with at least one
      Valine allele (P=0.037). This finding could reflect altered paclitaxel
      metabolism, however, the finding was independent of paclitaxel clearance.
      Alternatively, the role of CYP1B1 in estrogen metabolism may influence the risk
      of invasive or paclitaxel resistant breast cancer in patients carrying the
      CYP1B1*3 allele.

PMID- 17224915
TI  - Association of the mu-opioid receptor gene with smoking cessation.
AB  - We investigated the association of the OPRM1 genotype with long-term smoking
      cessation and change in body mass index (BMI) following a smoking cessation
      attempt among smokers who attempted to quit using the nicotine replacement
      therapy (NRT) patch or placebo in a randomized controlled trial, and were
      followed-up over an 8-year period following their initial cessation attempt. We
      also investigated possible sex differences in these relationships, given evidence
      for sex differences in smoking cessation and central opioid mechanisms, as well
      as some evidence for sex differences in response to NRT. Our results indicate
      that OPRM1 genotype may moderate the effect of transdermal nicotine patch
      compared to placebo during active treatment, with a benefit of active NRT
      treatment evident in the OPRM1 AA genotype group only and those carrying one or
      more copies of the G allele demonstrating no benefit of active NRT versus placebo
      patch. Our results also indicate a sex difference in change in BMI at 8-year
      follow-up following a smoking cessation attempt, with ex-smokers demonstrating an
      increase in BMI, and this increase being greater in female subjects than in male
      subjects. We did not observe any association of OPRM1 genotype with change in
      BMI, although there was a trend for genotype to influence the observed sex
      difference in change in BMI over time. Future studies should attempt to replicate
      these findings, and investigate the relationship between both short- and long
      term weight gain and smoking cessation and investigate possible mechanisms that
      may underlie these processes. Future studies should also investigate the role of
      OPRM1 genotype and smoking cessation on other appetitive and reward behaviours
      such as alcohol consumption.

PMID- 17224916
TI  - Identification of tightly regulated groups of genes during Drosophila
      melanogaster embryogenesis.
AB  - Time-series analysis of whole-genome expression data during Drosophila
      melanogaster development indicates that up to 86% of its genes change their
      relative transcript level during embryogenesis. By applying conservative
      filtering criteria and requiring 'sharp' transcript changes, we identified 1534
      maternal genes, 792 transient zygotic genes, and 1053 genes whose transcript
      levels increase during embryogenesis. Each of these three categories is dominated
      by groups of genes where all transcript levels increase and/or decrease at
      similar times, suggesting a common mode of regulation. For example, 34% of the
      transiently expressed genes fall into three groups, with increased transcript
      levels between 2.5-12, 11-20, and 15-20 h of development, respectively. We
      highlight common and distinctive functional features of these expression groups
      and identify a coupling between downregulation of transcript levels and targeted
      protein degradation. By mapping the groups to the protein network, we also
      predict and experimentally confirm new functional associations.

PMID- 17224917
TI  - Tissue-specific regulatory elements in mammalian promoters.
AB  - Transcription factor-binding sites and the cis-regulatory modules they compose
      are central determinants of gene expression. We previously showed that binding
      site motifs and modules in proximal promoters can be used to predict a
      significant portion of mammalian tissue-specific transcription. Here, we report
      on a systematic analysis of promoters controlling tissue-specific expression in
      heart, kidney, liver, pancreas, skeletal muscle, testis and CD4 T cells, for both
      human and mouse. We integrated multiple sources of expression data to compile
      sets of transcripts with strong evidence for tissue-specific regulation. The
      analysis of the promoters corresponding to these sets produced a catalog of
      predicted tissue-specific motifs and modules, and cis-regulatory elements.
      Predicted regulatory interactions are supported by statistical evidence, and
      provide a foundation for targeted experiments that will improve our understanding
      of tissue-specific regulatory networks. In a broader context, methods used to
      construct the catalog provide a model for the analysis of genomic regions that
      regulate differentially expressed genes.

PMID- 17224919
TI  - Experimental approaches to the study of HIV-1 latency.
AB  - Viral latency is a reversibly non-productive state of infection that allows some
      viruses to evade host immune responses. As a consequence of its tropism for
      activated CD4(+) T cells, HIV-1 can establish latent infection in resting memory
      CD4(+) T cells, which are generated when activated CD4(+) T cells return to a
      quiescent state. Latent HIV-1 persists as a stably integrated but
      transcriptionally silent provirus. In this state, the virus is unaffected by
      immune responses or antiretroviral drugs, and this latent reservoir in resting
      CD4(+) T cells is a major barrier to curing the infection. Unfortunately, there
      is no simple assay to measure the number of latently infected cells in a patient,
      nor is there an entirely representative in vitro model in which to explore the
      molecular mechanisms of latency. This Review will consider current approaches to
      the analysis of HIV-1 latency both in vivo and in vitro.

PMID- 17224920
TI  - Distribution, diversity and ecology of aerobic CO-oxidizing bacteria.
AB  - Numerous studies indicate that carbon monoxide (CO) participates in a broader
      range of processes than any other single molecule, ranging from subcellular to
      planetary scales. Despite its toxicity to many organisms, a diverse group of
      bacteria that span multiple phylogenetic lineages metabolize CO. These bacteria
      are globally distributed and include pathogens, plant symbionts and
      biogeochemically important lineages in soils and the oceans. New molecular and
      isolation techniques, as well as genome sequencing, have greatly expanded our
      knowledge of the diversity of CO oxidizers. Here, we present a newly emerging
      picture of the distribution, diversity and ecology of aerobic CO-oxidizing
      bacteria.

PMID- 17224918
TI  - Reconstructing dynamic regulatory maps.
AB  - Even simple organisms have the ability to respond to internal and external
      stimuli. This response is carried out by a dynamic network of protein-DNA
      interactions that allows the specific regulation of genes needed for the
      response. We have developed a novel computational method that uses an input
      output hidden Markov model to model these regulatory networks while taking into
      account their dynamic nature. Our method works by identifying bifurcation points,
      places in the time series where the expression of a subset of genes diverges from
      the rest of the genes. These points are annotated with the transcription factors
      regulating these transitions resulting in a unified temporal map. Applying our
      method to study yeast response to stress, we derive dynamic models that are able
      to recover many of the known aspects of these responses. Predictions made by our
      method have been experimentally validated leading to new roles for Ino4 and Gcn4
      in controlling yeast response to stress. The temporal cascade of factors reveals
      common pathways and highlights differences between master and secondary factors
      in the utilization of network motifs and in condition-specific regulation.

PMID- 17224921
TI  - RNA viruses: hijacking the dynamic nucleolus.
AB  - The nucleolus is a dynamic subnuclear structure with roles in ribosome subunit
      biogenesis, mediation of cell-stress responses and regulation of cell growth. The
      proteome and structure of the nucleolus are constantly changing in response to
      metabolic conditions. RNA viruses interact with the nucleolus to usurp host-cell
      functions and recruit nucleolar proteins to facilitate virus replication.
      Investigating the interactions between RNA viruses and the nucleolus will
      facilitate the design of novel anti-viral therapies, such as recombinant vaccines
      and therapeutic molecular interventions, and also contribute to a more detailed
      understanding of the cell biology of the nucleolus.

PMID- 17224922
TI  - Translational control of retroviruses.
AB  - All replication-competent retroviruses contain three main reading frames, gag,
      pol and env, which are used for the synthesis of structural proteins, enzymes and
      envelope proteins respectively. Complex retroviruses, such as lentiviruses, also
      code for regulatory and accessory proteins that have essential roles in viral
      replication. The concerted expression of these genes ensures the efficient
      polypeptide production required for the assembly and release of new infectious
      progeny virions. Retroviral protein synthesis takes place in the cytoplasm and
      depends exclusively on the translational machinery of the host infected cell.
      Therefore, not surprisingly, retroviruses have developed RNA structures and
      strategies to promote robust and efficient expression of viral proteins in a
      competitive cellular environment.

PMID- 17224923
TI  - Interleukin-6 gene amplification and shortened survival in glioblastoma patients.
AB  - Interleukin-6 (IL-6) is known to promote tumour growth and survival. We evaluated
      IL-6 gene amplification in tumours from 53 glioma patients using fluorescence in
      situ hybridisation. Amplification events were detected only in glioblastomas (15
      out of 36 cases), the most malignant tumours, and were significantly associated
      with decreased patient survival.

PMID- 17224924
TI  - Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta
      analysis.
AB  - We conducted a systematic review of the risk of pancreatic cancer in people with
      type I and young-onset diabetes. In three cohort and six case-control studies,
      the relative risk for pancreatic cancer in people with (vs without) diabetes was
      2.00 (95% confidence interval 1.37-3.01) based on 39 cases with diabetes.

PMID- 17224925
TI  - Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and
      neck.
AB  - Despite significant advances in the use of surgery, chemotherapy and radiotherapy
      to treat squamous cell carcinoma of the head and neck (SCCHN), prognosis has
      improved little over the past 30 years. There is a clear need for novel, more
      effective therapies to prevent relapse, control metastases and improve overall
      survival. Improved understanding of SCCHN disease biology has led to the
      introduction of molecularly targeted treatment strategies in these cancers. The
      epidermal growth factor receptor (EGFR) is expressed at much higher levels in
      SCCHN tumours than in normal epithelial tissue, and EGFR expression correlates
      with poor prognosis. Therefore, much effort is currently directed toward
      targeting aberrant EGFR activity (e.g. cell signalling) in SCCHN. This review
      discusses the efficacy of novel therapies targeting the EGFR (e.g. anti-EGFR
      antibodies and EGFR tyrosine kinase inhibitors) that are currently tested in
      SCCHN patients.

PMID- 17224926
TI  - Are exon 19 deletions and L858R EGFR mutations in non-small-cell lung cancer
      clinically different?

PMID- 17224927
TI  - Gemcitabine chemoresistance and molecular markers associated with gemcitabine
      transport and metabolism in human pancreatic cancer cells.
AB  - To identify predictive molecular markers for gemcitabine resistance, we
      investigated changes in the expression of four genes associated with gemcitabine
      transport and metabolism during the development of acquired gemcitabine
      resistance of pancreatic cancer cell lines. The expression levels of human
      equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (dCK), RRM1,
      and RRM2 mRNA were analysed by real-time light cycler-PCR in various subclones
      during the development of acquired resistance to gemcitabine. Real-time light
      cycler-PCR demonstrated that the expression levels of either RRM1 or RRM2
      progressively increased during the development of gemcitabine resistance.
      Expression of dCK was slightly increased in cells resistant to lower
      concentrations of gemcitabine, but was decreased below the undetectable level in
      higher concentration-resistant subclones. Expression of hENT1 was increased in
      the development of gemcitabine resistance. As acquired resistance to gemcitabine
      seems to correlate with the balance of these four factors, we calculated the
      ratio of hENT1 x dCK/RRM1 x RRM2 gene expression in gemcitabine-resistant
      subclones. The ratio of gene expression decreased progressively with development
      of acquired resistance in gemcitabine-resistant subclones. Furthermore, the
      expression ratio significantly correlated with gemcitabine sensitivity in eight
      pancreatic cancer cell lines, whereas no single gene expression level correlated
      with the sensitivity. These results suggest that the sensitivity of pancreatic
      cancer cells to gemcitabine is determined by the ratio of four factors involved
      in gemcitabine transport and metabolism. The ratio of the four gene expression
      levels correlates with acquired gemcitabine-resistance in pancreatic cancer
      cells, and may be useful as a predictive marker for the efficacy of gemcitabine
      therapy in pancreatic cancer patients.

PMID- 17224928
TI  - Pharmacokinetics and metabolism of 13-cis-retinoic acid (isotretinoin) in
      children with high-risk neuroblastoma - a study of the United Kingdom Children's
      Cancer Study Group.
AB  - The administration of 13-cis-retinoic acid (13-cisRA), following myeloablative
      therapy improves 3-year event-free survival rates in children with high-risk
      neuroblastoma. This study aimed to determine the degree of inter-patient
      pharmacokinetic variation and extent of metabolism in children treated with 13
      cisRA. 13-cis-retinoic acid (80 mg m(-2) b.d.) was administered orally and plasma
      concentrations of parent drug and metabolites determined on days 1 and 14 of
      courses 2, 4 and 6 of treatment. Twenty-eight children were studied. The
      pharmacokinetics of 13-cisRA were best described by a modified one-compartment,
      zero-order absorption model combined with lag time. Mean population
      pharmacokinetic parameters included an apparent clearance of 15.9 l h(-1),
      apparent volume of distribution of 85 l and absorption lag time of 40 min with a
      large inter-individual variability associated with all parameters (coefficients
      of variation greater than 50%). Day 1 peak 13-cisRA levels and exposure (AUC)
      were correlated with method of administration (P<0.02), with 2.44- and 1.95-fold
      higher parameter values respectively, when 13-cisRA capsules were swallowed as
      opposed to being opened and the contents mixed with food before administration.
      Extensive accumulation of 4-oxo-13-cisRA occurred during each course of treatment
      with plasma concentrations (mean+/-s.d. 4.67+/-3.17 microM) higher than those of
      13-cisRA (2.83+/-1.44 microM) in 16 out of 23 patients on day 14 of course 2.
      Extensive metabolism to 4-oxo-13-cisRA may influence pharmacological activity of
      13-cisRA.

PMID- 17224930
TI  - Mahogany, blood-brain barrier, and fat mass surge in AVY mice.
AB  - Avy/agouti (Avy) mice have late onset obesity related to overexpression of agouti
      signaling protein (ASP) in the hypothalamus. As mahogany modulates the actions of
      ASP, we tested the transport of mahogany peptide across the blood-brain barrier
      (BBB). The brain uptake of mahogany peptide was significantly higher in young Avy
      mice, and it preceded the surge of fat mass quantified by nuclear magnetic
      resonance. The results suggest a role of accelerated BBB transport in the
      epigenetics of Avy mice.

PMID- 17224929
TI  - Circulating endocannabinoid levels, abdominal adiposity and related
      cardiometabolic risk factors in obese men.
AB  - OBJECTIVE: The link between excess intra-abdominal adiposity (IAA) and metabolic
      complications leading to type 2 diabetes and cardiovascular disease is well
      recognized. Blockade of endocannabinoid action at cannabinoid CB(1) receptors was
      shown to reduce these complications. Here, we investigated the relationship
      between IAA, circulating endocannabinoid levels and markers of cardiometabolic
      risk in male obese subjects. DESIGN, SUBJECTS AND MEASUREMENTS: Fasting plasma
      levels of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2
      AG), were measured by liquid chromatography-mass spectrometry in a study sample
      of 62 untreated asymptomatic men with body mass index (BMI) from 18.7 to 35.2
      kg/m(2). RESULTS: Plasma 2-AG, but not AEA, levels correlated positively with
      BMI, waist girth, IAA measured by computed tomography, and fasting plasma
      triglyceride and insulin levels, and negatively with high-density lipoprotein
      cholesterol and adiponectin levels. Obese men with similar BMI values (> or =30
      kg/m(2)) but who markedly differed in their amount of IAA (< vs > or = 130 cm(2),
      n=17) exhibited higher 2-AG levels in the presence of high IAA. No difference in
      2-AG concentrations was observed between obese men with low levels of IAA vs
      nonobese controls. CONCLUSIONS: These results provide evidence for a relationship
      in men between a key endocannabinoid, 2-AG, and cardiometabolic risk factors,
      including IAA.

PMID- 17224931
TI  - No effect of dietary fat on short-term weight gain in mice treated with atypical
      antipsychotic drugs.
AB  - RATIONALE: Atypical antipsychotic drugs (AAD) induce significant weight gain in
      female C57BL/6J mice. The effect of dietary fat on weight gain and serum lipids
      in this model is unknown. OBJECTIVES: Test the hypothesis that the obesigenic
      effects of these drugs are greater in the presence of a high-fat diet. METHODS:
      Female C57BL/6J mice were treated with atypical antipsychotics for 3 weeks and
      fed either a low-fat or high-fat diet (4.6 vs 15.6% fat by wt). Food intake (FI),
      body weight (BW), body composition, and serum lipids were measured during
      treatment with optimized doses of olanzapine, quetiapine, and risperidone. Energy
      intake (EI) and feed efficiency (FE) were calculated. Group differences in change
      were analyzed via repeated measures analysis of variance (ANOVA). Serum lipid
      concentrations, EI and FE were compared using two-way ANOVA. RESULTS: AAD-treated
      mice gained significantly more weight than controls after 3 weeks (P<0.001).
      Treatment and diet had significant effects on FI and EI over time (P<0.001). AAD
      treated mice had significantly higher FE than controls (P<0.05); however, there
      was no significant drug by diet interaction (P=0.65). Risperidone low-fat mice
      gained significantly more absolute fat mass than placebo low-fat mice (P<0.05).
      All treatment groups, except quetiapine low-fat and olanzapine high-fat, gained
      significantly more absolute lean mass than placebo controls (P<0.05). Cholesterol
      levels were significantly lower in quetiapine and risperidone than placebo
      (P<0.05). Risperidone low-fat mice had significantly higher triglyceride levels
      than placebo and risperidone high-fat mice (P<0.05). CONCLUSIONS: A high-fat diet
      does not increase AAD-induced BW gain in female mice during a 3-week treatment
      period.

PMID- 17224932
TI  - Perceived and observed neighborhood indicators of obesity among urban adults.
AB  - OBJECTIVE: The global obesity epidemic has been partially attributed to modern
      environments that encourage inactivity and overeating, yet few studies have
      examined specific features of the physical neighborhood environment that
      influence obesity. Using two different measurement methods, this study sought to
      identify and compare perceived and observed neighborhood indicators of obesity
      and a high-risk profile of being obese and inactive. DESIGN: Cross-sectional
      telephone surveys (perceived) and street-scale environmental audits (observed)
      were conducted concurrently in two diverse US cities to assess recreational
      facility access, land use, transportation infrastructure and aesthetics.
      SUBJECTS: A total of 1032 randomly selected urban residents (20% obese, 32%
      black, 65% female). ANALYSIS: Bivariate and multivariate logistic regression
      analyses were conducted to estimate the association (adjusted prevalence odds
      ratio (aOR)) between the primary outcome (obese vs normal weight) and perceived
      and observed environmental indicators, controlling for demographic variables.
      RESULTS: Being obese was significantly associated with perceived indicators of no
      nearby nonresidential destinations (aOR=2.2), absence of sidewalks (aOR=2.2),
      unpleasant community (aOR=3.1) and lack of interesting sites (aOR=4.8) and
      observed indicators of poor sidewalk quality (aOR=2.1), physical disorder
      (aOR=4.0) and presence of garbage (aOR=3.7). Perceived and observed indicators of
      land use and aesthetics were the most robust neighborhood correlates of obesity
      in multivariate analyses. CONCLUSIONS: The findings contribute substantially to
      the growing evidence base of community-level correlates of obesity and suggest
      salient environmental and policy intervention strategies that may reduce
      population-level obesity prevalence. Continued use of both measurement methods is
      recommended to clarify inconsistent associations across perceived and observed
      indicators within the same domain.

PMID- 17224933
TI  - Coexistence of maternal central adiposity and child stunting in Mexico.
AB  - OBJECTIVE: To assess the coexistence of maternal adiposity and child stunting
      (CS) in Mexico, estimate its national prevalence and identify the associated
      socio-demographic factors. METHODS: A secondary analysis from the Mexican
      Nutrition Survey 1999, a nationally representative survey, was conducted. Mother
      and children subsamples were matched and a total of 6225 mother/child pairs were
      obtained. Stunting was defined as height-for-age z-scores <-2.0. Maternal body
      mass index (BMI) was classified according to World Health Organization
      recommended cutoff points. Waist-to-hip ratio (WHR) was calculated by dividing
      waist by hip circumferences. Logistic regression models were fitted to explore
      the coexistence of CS and maternal central adiposity (MCA) (WHR> or =0.85) while
      controlling for biological and socio-demographic factors. RESULTS: A total of
      5974 pairs had complete information. MCA coexisted with CS in 6.2% of the
      mother/child pairs. The phenomenon was more prevalent in rural locations, in the
      south region and among indigenous families (14.5, 12.5 and 23.9%). After
      controlling for child age and maternal BMI, a 78% increase in the likelihood of
      CS was related to maternal WHR > or =0.85 (odds ratio (OR)=1.78, 95% confidence
      interval (CI)=1.53, 2.10). After controlling for maternal height, the magnitude
      of the OR decreased (OR=1.33, 95%CI=1.13, 1.57), but remained significant.
      Therefore, it is suggested that women with a WHR approximately 1 have had twice
      the probability of having a stunted child as those with a WHR of 0.65.
      CONCLUSION: Although MCA and CS are two conditions frequently regarded as result
      of opposite determinants, our observation suggests that this is not necessarily
      the case, particularly in populations undergoing the nutrition transition. MCA
      was associated not only to chronic diseases, but also to child stunting.

PMID- 17224934
TI  - Oestrogen receptor alpha gene expression levels are reduced in obese compared to
      normal weight females.
AB  - OBJECTIVE: To determine whether oestrogen receptor (ER)alpha messenger RNA (mRNA)
      levels or single nucleotide polymorphisms (SNPs) are associated with obesity in
      Swedish women. DESIGN: ERalpha mRNA expression levels were measured by real-time
      qPCR in subcutaneous adipose tissue from non-obese (N=16, BMI<30) and obese
      (N=17, BMI>or=30) women. In addition, ERalpha mRNA expression levels were
      determined in isolated adipocytes. ERalpha promoter usage was characterized by 5'
      RACE and by real-time qPCR in subcutaneous adipose tissue from the same non-obese
      and obese women. Two ERalpha SNPs were scored in 509 non-obese and 489 obese
      females. RESULTS: ERalpha mRNA expression levels were lower in obese compared to
      non-obese women in both subcutaneous adipose tissue and in adipocytes. We show
      that two ERalpha promoters are differentially utilized in obese and non-obese
      individuals. We did not find any significant association between obesity and the
      ERalpha SNPs or haplotypes assayed. CONCLUSION: The reduced ERalpha mRNA levels
      observed in adipose tissue from obese compared to non-obese women support a role
      for oestrogen signaling via ERalpha, in control of body weight. Mechanistic
      studies of the role of ERalpha in adipocytes and how its expression is regulated
      in relation to fat mass should be performed. The latter studies should focus on
      the two promoters that are used differently in obese and non-obese individuals.

PMID- 17224935
TI  - [Neuroprotective and neurorestorative therapies for the treatment of Parkinson's
      disease].
AB  - Parkinson's disease is the second most common neurodegenerative disorder after
      Alzheimer's disease. Current therapies are symptomatic and, although these
      therapies are efficacious during the early stages of the disease, they present
      important side effects when they are used for a long time. The ideal therapy
      would be the one that would slow down or stop the progression of the disease.
      This can be achieved, for instance, with neuroprotective and neurorestorative
      therapies. Among them, cell therapy and therapy with trophic factors such as
      glial cell line derived neurotrophic factor (GDNF) are the most challenging and
      promising ones for the scientific community. Although the use of GDNF as a
      treatment for Parkinson s disease was proposed several years ago, it is necessary
      to develop alternative strategies to deliver GDNF appropriately to concrete areas
      of the brain. Here, the use of microspheres as the most suitable tool for the
      administration of this neurotrophic factor is discussed.

PMID- 17224936
TI  - [Modulation of gastrointestinal physiology through probiotic strains of
      Lactobacillus casei and Bifidobacterium bifidum].
AB  - The products called functional foods, which besides being merely nutritional have
      different beneficial effects on the organism, are situated in the context of diet
      and health promotion. Amongst these functional foods we can distinguish, amongst
      others, between probiotic and prebiotic compounds. The micro-organisms most
      widely used in probiotic foods belong to the Lactobacillus and Bifidobacterium
      types. In this article we have studied the effect of diets supplemented with
      Lactobacillus casei or Bifidobacterium bifidum on animal development and
      especially on the intestinal function, centred on their immune, digestive and
      absorptive activity in growing animals. The bacteria strains used modify the
      activity of the small intestine of healthy mice, significantly affecting their
      enzymatic activity (sucrase, maltase and aminopeptidase) and the collection of
      nutrients (galactose and glycilsarcosine), as well as the intestinal immune
      activity (higher number of Peyer's patches). However, these effects do not appear
      to disturb the development of the growing animals since no significant
      differences are appreciated in their body weight or in their blood parameters.
      These results make clear the possible beneficial effects on intestinal physiology
      and contribute to the understanding of the possible mechanisms of action of the
      probiotics, which could be employed in the preventive treatment of different
      pathologies related to the digestive apparatus.

PMID- 17224937
TI  - [Recent trends of the main causes of death in Navarre. 1995-2004].
AB  - We present the statistics for mortality in Navarre for the 1995-2004 period by
      sex, age and cause of death. METHODS: The data proceeds from the statistical
      bulletins on death. The 1995-1999 period is compared with the 2000-2004 period,
      using adjusted rates to the population of Navarre for the year 2001 and the rate
      of potential years of life lost between 0-70 years adjusted to the European
      population. RESULTS: Life expectancy at birth in the 2000-2004 period was 77.9
      years in men and 85 years in women, the latter being one of the highest
      registered at the world level. Infant mortality fell to 3.3 per 1,000 living
      newborn infants. The risk of death has fallen in practically all age groups, with
      a notable fall in mortality of 40% in the 25-34 group at the cost of AIDS. There
      has been a significant increase of mortality due to lung cancer amongst women
      under 65 years of age (46%) in the 2000-2004 period with respect to the previous
      five year period and a sharp fall in mortality due to breast cancer (45.4%). In
      both sexes there has been a continued fall of mortality due to cerebrovascular
      diseases, ischaemic heart diseases, cardiac failure and arteriosclerosis and of
      mortality due to ulcer and cirrhosis. The rates of mortality in Navarre in all
      the main groups of causes are lower than those of Europe, except for the rate of
      mortality due to external causes. CONCLUSIONS: The increase of mortality due to
      lung cancer and other cancers related to smoking, due to the spread of
      consumption in recent decades, could have a negative influence on the life
      expectancy of women in Navarre in coming years. The prevention of mortality due
      to external causes and the prevention of deaths linked to tobacco consumption are
      the two priorities that emerge from the data on mortality in this autonomous
      community.

PMID- 17224938
TI  - [Modulation of biomarkers expression (OR, PR and C-erbB2) in breast cancer
      following neoadjuvant treatment].
AB  - INTRODUCTION: Pre and post-operative oncological therapy in patients with breast
      cancer is determined, amongst other factors, by hormone receptor status and by c
      erbB2 expression. The aim of this study is to determine the influence of
      neoadjuvant therapy on the expression of oestrogen receptor (OR), progesterone
      receptor (PR) and c-erbB2. METHODS: Fifty-three patients with breast cancer
      diagnosed by tru-cut biopsy were studied. Patients with locally advanced
      carcinoma (20) had preoperative treatment. All patients underwent surgical
      resection. Expression of OR, PR and c-erbB2 in both the tru-cut biopsy and the
      gross specimen was compared. RESULTS: We found significant differences in OR, PR
      expression in both biopsy and gross specimen, between the group of patients who
      underwent neoadjuvant treatment and the group without pre-surgical treatment.
      Changes in PR, OR and c-erbB2 status were found between the tru-cut biopsy and
      the gross specimen, in about 10 to 40% of the cases who received neoadjuvant
      therapy. These changes had no statistical significance.

PMID- 17224939
TI  - [Knowledge, conduct and opinions of health professionals concerning
      confidentiality at a hospital].
AB  - BACKGROUND: To analyse the knowledge, conduct and opinions concerning
      confidentiality of the medical and nursing personnel who attended the 13 seminars
      given on this subject at the Virgen del Camino Hospital in Pamplona in the year
      2002. METHODS: Distribution before the start of each seminar of a survey of 11
      closed questions to be completed anonymously. RESULTS: Ninety-three percent
      (93.0%) of the 244 professionals attending the seminars responded to the survey
      (128 doctors and 99 nurses). Ninety-two point one percent (92.1%) of the
      professionals understand what privacy is, but 58.1% do not know any of the laws
      that regulate it. Eighty-seven point five percent (87.5%) know when it is
      legitimate to access the data on a patient, but contrary conduct is recognise in
      a percentage that increases with age, from 12.5% in the group under 31 years old
      to 51.9% in those over 50 years of age. More correct practices were recollected
      amongst nursing personnel even when they show less theoretical knowledge about
      these questions. Forty-nine point seven percent (49.7%) of the professionals
      would join another centre if they wanted their diagnosis not to be divulged
      amongst their colleagues, and 92.2% consider informal comments made in the
      corridors to be the most frequent way of breaking confidentiality in the
      hospital. CONCLUSION: It seems timely to call attention to ethical and legal
      responsibility in our hospital and to encourage reflection amongst professional
      about this questions of confidentiality in order to improve this key dimension of
      health care.

PMID- 17224940
TI  - [Treatment of perianal Crohn's disease].
AB  - Perianal affectation due to Crohn's disease includes a wide spectrum of lesions
      involving different management and prognosis. A thorough exploration of the
      patient, under anaesthetic if necessary, a rectoscope to evaluate the possible
      affectation of the rectum by the disease, and on occasions evaluation through
      endoanal echography or magnetic resonance, are the bases for a correct diagnostic
      and therapeutic focus. Pharmacology and surgery must be complementary in the
      treatment of perianal Crohn's disease and must pursue a double aim: to alleviate
      the symptomology of the patient and prevent possible complications. Except in
      situations of emergency due to perianal sepsis, medical treatment is the first
      step in managing perianal Crohn's disease, and on many occasions it will control
      the disease, making surgery unnecessary. When surgery is required, with the aim
      of a definitive treatment of the perianal lesion, the risk of developing
      complications, especially incontinence, must be contrasted.

PMID- 17224941
TI  - [Operational research in the Health Sciences: Are these techniques appreciated in
      the current literature?].
AB  - The aim of this article is to present the uses of operational research in the
      health sciences, both in the field of the organisation and management of health
      resources and in the field of prevention, detection and treatment of diseases. we
      concentrate on application, without entering into the technical details of the
      mathematical models or the methods of resolution.

PMID- 17224942
TI  - [Is thyroid function screening warranted during pregnancy?].

PMID- 17224943
TI  - [Primary pyomyositis of the psoas muscles in a temperate climate. Review of two
      cases in children followed up over the long term].
AB  - BACKGROUND: We review two cases of primary pyomyositis of the psoas in children
      that occurred in Navarre, their management and long-term evolution. Primary
      pyomyositis of the psoas muscle is a rare infection in a temperate climate. Its
      diagnosis is difficult due to the similarity of the symptoms with several
      infectious processes, mainly septic arthritis of the hip in children and
      adolescents. The rarity of the present cases is due to several facts: occurrence
      in children, in a temperate climate (Navarre), immunocompetent patients and
      without subjacent pathology, besides their monofocal situation that is contrary
      to the more frequent multifocal presentation. These factors, besides the poor
      specificity of the symptoms, constitute a diagnostic challenge. METHODS: We
      present two patients (10 and 12 years old) with fever and a painful hip. Neither
      of the patients had predisposing factors. Both of them showed hip flexion with
      limited range of motion in rotations. Confirmation of the diagnosis was made by
      ultrasound, CT-scan and/or MRI. Needle aspiration of the hip, under general
      anaesthesia, confirmed the reactive origin of the joint effusion in both
      patients. In neither of the two cases was there a significant diagnostic delay.
      Staphylococcus aureus was isolated in the purulent material in one case and in
      the hemoculture in the other. Both patients have been checked in a long-term
      revision (follow-up of 7 and 10 years). RESULTS: They were successfully treated
      by isolated antibiotherapy in one case and surgical drainage in the other.
      Healing was achieved in each case without relapse or sequels in a long-term
      revision. We carry out a global revision of this rare infection, emphasising the
      difficulty of its clinical diagnosis and the different treatment modalities and
      the proper indication. We suggest an algorithm as a clinical guide for its
      clinical-therapeutic management.

PMID- 17224944
TI  - [Multiple symmetric lipomatosis: a case report].
AB  - We present the case of a 46 year-old man with Multiple Symmetric Lipomatosis
      (MSL), an infrequent disease with an unknown aetiology. MSL is characterized by
      multiple masses of adipose tissue and it is usually associated with alcoholism,
      metabolic disorders and neuropathy. We describe the clinical-morphological
      characteristics of the lesions it presents, the exploratory findings, cervical
      CAT, the analytical results and the results of subcutaneous biopsy. MSL type I
      disease was diagnosed. The treatment of choice, the lipectomy, was performed,
      making it possible to obtain a substantial disease improvement, both physical and
      aesthetically.

PMID- 17224945
TI  - [Haemorrhagic exanthema due to dengue virus induced by acetylsalicylic acid].
AB  - Dengue fever, a viral infectious disease characteristic of tropical climates, is
      considered to be a re-emergent pathology responsible for several serious
      outbreaks in the last decade. Some factors have been involved in the spread of
      the virus and its vectorial mosquito carrier: human alteration of the ecosystems,
      improvement and speed in the transit of goods and people and climate changes. As
      a reflection of this, an increase in imported cases is probable, especially in
      tourists coming from endemic areas, considering its short period of incubation (7
      10 days). The recognition of personal antecedents of journeys, the main symptoms
      of the disease and the potential presence of complications (haemorrhagic dengue)
      should be included in the examination of fever of unknown origin or feverish
      exanthema. The case of a patient is presented whose clinical picture of classic
      dengue fever was worsened by self-treatment with acetylsalicylic acid.

PMID- 17224946
TI  - Impact of VISION 2020 on global blindness.

PMID- 17224948
TI  - Demographics of corneal transplantation in Canada in 2004.
AB  - BACKGROUND: Penetrating keratoplasty (PKP) is the most frequently performed
      transplant surgery, and one of the most successful, yet no national study on the
      demographics of corneal transplantation in Canada has been published to date. The
      objectives of this study were to determine demographics of Canadian corneal
      transplant surgeons, donor tissue availability and waitlist length for each
      province, and limiting factors for the number of PKPs performed in Canada.
      METHODS: An anonymous voluntary survey of all Canadian corneal transplant
      surgeons was conducted between June and September 2004, with a concurrent
      voluntary survey of all eye banks in Canada. RESULTS: In 2004, there were 76
      corneal transplant surgeons distributed as follows: British Columbia 17.1%,
      Alberta 11.8%, Saskatchewan 3.9%, Manitoba 7.9%, Ontario 36.8%, Quebec 17.1% and
      the Atlantic provinces 5.3%. The response rate of the Canadian corneal transplant
      surgeon survey was 69.7%. On average, each respondent performed 1 (SD 1)
      PKP/week, 40 (33) PKPs/year, and had a waitlist of 50 (63) patients. The mean
      wait time from date of referral to initial consultation was 10 (SD 7) weeks and
      from time of diagnosis to PKP was 51 (32) weeks. The most significant
      contributing factor to PKP waitlist selected by respondents in all provinces
      except Ontario was donor tissue shortage (64.7%); Ontario respondents (81.0%)
      believed that insufficient operating room time was the main factor. Ontario was
      the only province where all corneal transplant surgeons scheduled PKP electively
      and where surplus corneal tissue was regularly exported. INTERPRETATION:
      Recommendations include standardizing the criteria for acceptable donor tissue
      across all eye banks in Canada to increase efficiency of distribution,
      introducing and properly implementing mandatory referral and request legislation
      to increase donor rates, and increasing availability of operating room time for
      corneal transplant surgeons, especially in Ontario.

PMID- 17224949
TI  - Topical 2% cyclosporine A in preservative-free artificial tears for the treatment
      of vernal keratoconjunctivitis.
AB  - BACKGROUND: A double-masked, placebo-controlled trial to evaluate the short-term
      efficacy and safety of topical 2% cyclosporine A in preservative-free artificial
      tears for patients with vernal keratoconjunctivitis. METHODS: Twenty patients
      with severe vernal keratoconjunctivitis were included in the study. All were
      treated with topical 2% cyclosporine A eye drops. One eye of each patient was
      administered 2% cyclosporine A in preservative-free artificial tears; the fellow
      eye received the placebo (vehicle) for the first 2 weeks, in a double-masked,
      placebo-controlled trial. Thereafter, the placebo eye received cyclosporine A
      (open trial). Symptoms and signs were scored on the day of enrollment and at the
      end of week 2, 4, and 14. RESULTS: At the end of week 2, no statistically
      significant decrease was noted from baseline in mean scores of either signs (p =
      0.18) or symptoms (p = 0.50) in the eyes that received placebo. On the other
      hand, a statistically significant decrease was observed in both sign and symptom
      scores (p < 0.001, for both) of eyes that received cyclosporine A. Significant
      differences were also noted at 2 weeks in mean scores of both signs and symptoms
      (p < 0.001, for both) between the eyes that received cyclosporine A and those
      that received placebo. At week 4 and 14, statistically significant decreases in
      both sign scores and symptom scores were noted compared with baseline in the eyes
      that received cyclosporine A and in the eyes that had initially received placebo
      (p < 0.001, for all). INTERPRETATION: Topical 2% cyclosporine A in preservative
      free artificial tears is effective in alleviating signs and symptoms of patients
      with severe vernal keratoconjunctivitis and had no observed side effects over the
      course of the study.

PMID- 17224950
TI  - Cystoid macular edema after phacoemulsification: risk factors and effect on
      visual acuity.
AB  - BACKGROUND: To determine the incidence and risk factors for cystoid macular edema
      (CME) after phacoemulsification surgery and its effect on visual acuity. METHODS:
      This prospective study evaluated 98 eyes of 98 patients (43 women) with a mean
      (SD) age of 61.8 (11.3) years. Phacoemulsification was performed with temporal
      clear corneal incision and implantation of foldable hydrophilic acrylic
      intraocular lens in the bag. Postoperative visits were on day 1, week 1, and at
      1, 3, and 6 months. In addition, at week 10 all patients had fundus fluorescein
      angiography, and presence of CME was determined. Age, sex, iris colour,
      pseudoexfoliation, type of cataract, phaco time, status of the posterior
      vitreous, iris trauma, severity of anterior chamber reaction, and visual acuities
      were evaluated. RESULTS: No major intraoperative complications occurred. Twenty
      five (25.5%) eyes were CME(+), and 73 (74.4%) eyes were CME(-). CME occurred in
      70% of patients with iris trauma and 20.5% of patients with no iris trauma. CME
      was more common in patients who had postoperative anterior chamber inflammation
      of 2+ or more than in patients with less inflammation (43.2% vs. 11.5%). Complete
      posterior vitreous detachment had some apparent protective effect against CME
      development. The mean visual acuities of CME(+) patients were lower than those of
      CME(-) patients in all postoperative periods. The difference was significant in
      the third month (p < 0.05). INTERPRETATION: CME after phacoemulsification was
      associated with iris trauma and severe postoperative inflammation. Complete
      posterior vitreous detachment had some apparent protective effect against CME
      development. CME may be associated with decreased visual acuity.

PMID- 17224951
TI  - Clinical outcome study of a modified surgical technique for pterygium excision.
AB  - BACKGROUND: Pterygium is a common condition that has many and varied surgical
      management techniques. Our aim was to describe and evaluate the safety and
      efficacy of a modified tissue-sparing surgical procedure for management of
      pterygium. METHODS: This was a retrospective, clinical outcome study of 67
      consecutive pterygium head excisions and mini inferior conjunctival autografts
      (PHEMICA), performed by a single senior surgeon over 7 years. The technique
      evaluated was a modified pterygium head removal and inferior conjunctival
      autograft, maximising host tissue preservation. RESULTS: Group A (primary
      pterygia): 5.25% recurrence rate (3 of 57 eyes). Group B (recurrent pterygia):
      30% recurrence rate (3 of 10 eyes). No major complications occurred. One partial
      autograft necrosis was noted (1.5%, 1 of 67 eyes), with full resolution.
      INTERPRETATION: The described technique is fast, safe, and effective with a 5.25%
      recurrence rate in those with primary pterygia. It is not, however, recommended
      in the treatment of recurrent pterygia; this group of patients requires a more
      radical excision with a larger autograft and the use of adjuncts such as
      mitomycin C.

PMID- 17224952
TI  - Screening for glaucoma in Canada: a systematic review of the literature.
AB  - BACKGROUND: To provide a recommendation on screening for glaucoma in Canada based
      on a review of recent evidence available in the literature. METHODS: A systematic
      literature review was performed to identify publications from MEDLINE, EMBASE,
      HealthSTAR, and Cochrane databases from 1990 to 2005. Relevant articles were
      categorized as economic studies, epidemiologic and intervention studies, or
      policy papers. Web sites and publications from provincial, state, national, and
      international health authorities were reviewed for policy recommendations and
      guidelines. RESULTS: We identified 39 articles (34 epidemiology and intervention,
      and 5 economic studies) for the review. From the economic studies, 2 were simple
      cost analyses and 3 were full economic evaluations (cost-effectiveness). Gaps
      were observed from these economic studies, where incremental cost-effectiveness
      analyses of modelled screening programmes were not observed. A large number of
      alternatives (i.e., screening techniques) and diverse outcome measures were found
      in the 34 epidemiology and intervention studies. This shows that evidence on the
      effectiveness of glaucoma screening programmes is available to be used in future
      modelled analyses. Neutral recommendation made by the Canadian Task Force on
      Periodic Health Examination regarding glaucoma screening in Canada could be
      related to the lack of reliable data and models used in past cost-effectiveness
      analyses. INTERPRETATION: A need exists to reevaluate the cost-effectiveness of a
      screening programme for glaucoma in Canada with updated efficacy and cost data.
      Health and monetary benefits could be improved compared with current practice and
      decision-makers would have the best available data when reevaluating the policy
      on screening for glaucoma.

PMID- 17224953
TI  - Comparison of Proview phosphene tonometry with Goldmann applanation tonometry.
AB  - BACKGROUND: To compare intraocular pressures obtained using a handheld pressure
      phosphene tonometer (PPT) (Proview, Bausch & Lomb Pharmaceuticals, Inc., Tampa,
      Fla.) with Goldmann applanation tonometry. METHODS: Comparative case series of 30
      randomly selected patients. RESULTS: The readings obtained with the pressure
      phosphene tonometer display a higher mean and a larger standard deviation than
      those obtained with the Goldmann applanation tonometer (GAT). Differences between
      PPT and GAT readings tended to decrease as a function of increased Goldmann
      levels. The relation of Proview and Goldmann readings (r = 0.32) and the
      scatterplot were not consistent with the hypothesis that the 2 methods are
      equivalent. INTERPRETATION: Our results indicate that the pressure phosphene-type
      handheld tonometry method, which does not appear to provide an accurate and
      consistent measure of intraocular pressure, is substantially less reliable than
      the Goldmann method.

PMID- 17224954
TI  - Benefits of stereopsis when identifying clinically significant macular edema via
      teleophthalmology.
AB  - BACKGROUND: The need to incorporate stereopsis into a teleophthalmology system is
      controversial. Detection of hard exudate in the macula is suggested by some as an
      adequate surrogate for direct observation of retinal thickening. This study was
      designed to determine how accurate the detection of hard exudate is as a
      surrogate for stereoscopic detection of clinically significant macular edema
      (CSME). METHODS: 120 patients with diabetes underwent clinical retinal
      examination with contact-lens biomicroscopy by a retinal specialist. The presence
      or absence of CSME was recorded. On the same day as clinical grading, 30 degrees
      stereoscopic digital photographs of the macula were captured. At least 2 months
      after clinical examination, the digital images were viewed by masked graders for
      the presence or absence of hard exudate and retinal thickening. RESULTS: 207 eyes
      of 106 patients had complete data sets for both diagnostic modalities. The
      sensitivity of hard exudate (93.9%) in predicting the presence of CSME was
      similar to that of direct stereoscopic observation of retinal thickening (90.9%),
      with p = 0.5. On the other hand, digital stereopsis was significantly more
      specific (92.9%) than was hard exudate (81.6%) in predicting the presence of CSME
      (p < 0.001). This difference was maintained even when controlling for image
      quality. INTERPRETATION: Although the presence of hard exudate within the macula
      is a sensitive surrogate marker for CSME, it is less specific than stereoscopic
      evaluation. Any American Telemedicine Association category 3 teleophthalmology
      system that utilizes hard exudate as a surrogate marker for CSME may refer
      patients unnecessarily for clinical evaluation.

PMID- 17224955
TI  - Orbital and muscle involvement in multiple myeloma.
AB  - CASE REPORT: We report 2 cases of orbital plasmacytoma in patients with known
      multiple myeloma. Orbital spread with secondary maxillary sinus involvement is
      reported in the first case. Case 2 is the first report of immunoglobulin A kappa
      light chain multiple myeloma involving orbital recti muscles. Computed axial
      tomography and magnetic resonance imaging aided the diagnosis, confirmed with
      histopathologic studies. COMMENTS: Extraskeletal spread is rare and orbital
      involvement is exceedingly uncommon. From a review of the literature since 1972,
      we conclude that the immunoglobulin G type of multiple myeloma, whether lambda or
      kappa light chain, may be a risk factor for orbital involvement.

PMID- 17224956
TI  - Gamma interferon assay as an alternative to PPD skin testing in selected patients
      with granulomatous intraocular inflammatory disease.
AB  - BACKGROUND: To evaluate the QuantiFERON-TB test (gamma interferon assay),
      approved by the Centers for Disease Control and Prevention for the detection of
      latent tuberculosis (LTB), in patients who potentially may require
      immunosuppressive therapy for ocular inflammatory disease. METHODS: Blood samples
      from 12 consecutive patients with granulomatous ocular inflammatory disease were
      evaluated first with the purified protein derivative (PPD) skin test and then
      with the QuantiFERON-TB test (11 of 12 patients, 1 declined). The results of the
      2 tests in both U.S.- and non-U.S.-born patients were compared with their
      Bacillus Calmette-Guerin (BCG) vaccination status and chest x-rays. RESULTS: In
      our small series there was a high degree of concordance between the QuantiFERON
      TB assay and the PPD skin test. INTERPRETATION: The QuantiFERON-TB test did not
      demonstrate intrinsic merit over PPD skin testing for screening for LTB in
      selected patients when immunosuppressive therapy is considered. The confounding
      effect of BCG vaccination renders interpretation of both tests difficult. Early
      reports suggest the second-generation tests that are now available may hold
      promise for use in the uveitis clinic and should be formally evaluated.

PMID- 17224957
TI  - Ocular manifestations of dengue fever in an East Indian epidemic.
AB  - BACKGROUND: The incidence and geographic distribution of dengue has increased
      dramatically in recent years. Previously, ocular findings in dengue fever were
      considered rare. We report a spectrum of ocular manifestations of this
      potentially fatal disease and its association with laboratory parameters.
      METHODS: 134 patients hospitalized with a diagnosis of dengue fever during an
      epidemic were included. Systemic and ophthalmic examinations were completed on
      all patients. RESULTS: The mean age was 31.3 years and 63.4% were males. All
      patients presented with fever. Six (4.5%) patients had retrobulbar pain and none
      of the patients presented with any visual complaints. Ocular findings were
      present in 54 (40.3%) patients. Subconjunctival haemorrhage was the commonest eye
      finding seen in 50 patients, of whom 84% had characteristic petechial type of
      haemorrhages. Fundus findings present in 10 (7.5%) patients included dilatation
      and tortuosity of vessels, superficial retinal haemorrhages, cotton-wool spots,
      and hard exudates; the macula, however, was spared in all patients. Only 6 of the
      patients with posterior segment involvement returned for follow-up examination
      and it was found that retinal changes had resolved without any specific treatment
      within 2 to 8 weeks time. Of all laboratory parameters evaluated, marked
      thrombocytopenia (platelet count <50,000/microL) emerged to be significantly
      associated with ocular haemorrhage. INTERPRETATION: Multiple subconjunctival
      haemorrhages, especially petechial type, are a common manifestation of dengue
      infection. Dengue fever patients with marked thrombocytopenia are predisposed to
      spontaneous ocular haemorrhages.

PMID- 17224958
TI  - Elevated intravitreal interleukin-6 levels in patients with proliferative
      diabetic retinopathy.
AB  - BACKGROUND: We conducted this study to elucidate the possible role of interleukin
      6 (IL-6) in the pathogenesis of proliferative diabetic retinopathy (PDR).
      METHODS: Together with pertinent clinical and laboratory data, intravitreal and
      serum concentrations of IL-6 were determined in 8 patients with PDR by means of
      enzyme-linked immunosorbent assay (ELISA). The results were compared with data
      from 8 nondiabetic control subjects undergoing vitrectomy. RESULTS: Significantly
      higher intravitreal IL-6 concentrations were found in patients with PDR (mean
      [SD], 755 [177] pg/mL) compared with control subjects (93 [151] pg/mL) (p =
      0.001). The serum IL-6 levels in the PDR group were lower than the measurable
      threshold of the ELISA kit (<0.16 pg/mL). Diabetic patients with macular edema
      had a higher mean (SD) level of intravitreal IL-6 (896 [73] pg/mL) compared with
      patients without macular edema (613 [119] pg/mL) (Mann-Whitney U test, p = 0.03).
      Correlation analysis did not reveal any significant association between
      intravitreal IL-6 levels and patient age, duration of either diabetes mellitus or
      vitreous hemorrhage, panretinal photocoagulation, type of current medical
      therapy, hyperglycemia, or the biochemical indicators of renal function.
      INTERPRETATION: IL-6, a proinflammatory cytokine, may have a role in PDR.
      Intraocular production of IL-6 appears to be responsible for the elevated
      intravitreal levels observed.

PMID- 17224960
TI  - Multiple bilateral primary cysts of the iris pigment epithelium.
AB  - CASE REPORT: Diagnostic and therapeutic considerations in the case of a 57-year
      old man with multiple iris cysts in both eyes. COMMENTS: Small and hidden from
      view, most primary iris cysts of the iris pigment epithelium remain clinically
      silent. Larger cysts may be noted on examination, but often remain difficult to
      visualize due to their location. By providing a high-resolution view of the iris
      and ciliary body, ultrasound biomicroscopy is a useful adjunct to the clinical
      examination in distinguishing primary cysts of the iris pigment epithelium from
      solid uveal neoplasms.

PMID- 17224959
TI  - Characterization of lymphoproliferative lesions of the conjunctiva:
      immunohistochemical and molecular genetic studies.
AB  - BACKGROUND: Conjunctival lymphoproliferative lesions have not been selected for
      independent analysis with newer immunohistochemical and molecular genetic
      techniques to highlight their unique profile. METHODS: Retrospective case series
      examined biopsies from 16 consecutive patients with conjunctival
      lymphoproliferative lesions. The histopathologic, immunohistochemical, and
      molecular genetic features were characterized, as well as the frequency of tumour
      type, prognostic implications, clinical features, and treatments offered.
      RESULTS: The diagnosis was lymphoma in 12 cases, atypical lymphoid hyperplasia
      (ALH) in 1 case, and reactive lymphoid hyperplasia (RLH) in 3 cases. The primary
      lymphomas consisted of 4 mucosa-associated lymphoid tissue lymphomas (MALTL), 1
      follicular lymphoma (FL), 2 diffuse large B-cell lymphomas (DLBCLs), 1
      lymphoplasmacytic lymphoma, and 1 T-cell lymphoma. Primary lymphomas were treated
      with radiation (n = 7), surgery (n = 1), and topical chemotherapy (n = 1).
      Complete remission was achieved in 8 of 9 primary lymphomas. Two cases of
      recurrence to the other conjunctiva were treated with radiation and both remained
      disease free. Secondary lymphomas included 2 DLBCL and 1 MALTL. Complete
      remission was seen in 2 patients after radiation plus chemotherapy, while the
      patient treated with chemotherapy alone was lost to follow-up. The 1 case of ALH
      presented bilaterally and achieved complete remission after topical chemotherapy
      treatments. The 3 RLH cases were surgically managed and 2 of the 3 recurred and
      were subsequently excised. Eleven lymphomas were of B-cell lineage by
      immunophenotyping. Molecular genetic studies of immunoglobulin heavy chain (IgH)
      gene rearrangement by polymerase chain reaction (PCR) showed clonal bands in 6 of
      12 lymphomas, 1 of 3 RLH (polyclonal by immunophenotyping) and 1 ALH. BCL2-IgH
      [t(14;18)] rearrangement was seen in 8 of 12 cases (1 FL, 3 DLBCLs, 4 MALTLs) by
      real-time quantitative PCR. INTERPRETATION: Conjunctival lymphomas are
      predominantly B-cell type with a high prevalence of MALTL. An unexpected finding
      was the BCL2-IgH rearrangement seen in 4 of 5 MALTL cases in our series. The
      significance of this remains unclear.

PMID- 17224961
TI  - Vitreopapillary traction: cost-effective diagnosis by optical coherence
      tomography.
AB  - CASE REPORTS: A prospective, noncomparative, observational case series. Three
      patients, aged 76 to 81, all referred to subspecialty services for evaluation of
      optic disc elevation, and all were found to have optic disc (vitreopapillary)
      traction as verified by optical coherence tomography. COMMENTS: Vitreopapillary
      traction is a recently recognized syndrome characterized by incomplete posterior
      vitreous detachment. The use of optical coherence tomography is helpful in the
      diagnosis of this syndrome, preventing many costly, unwarranted evaluations.

PMID- 17224962
TI  - Optic neuropathy in refractory neurosarcoidosis treated with TNF-alpha
      antagonist.
AB  - CASE REPORT: To report a rare case of optic neuropathy in refractory
      neurosarcoidosis treated with tumour necrosis factor-alpha antagonist
      (infliximab) perfusion. A 41-year-old man with diabetes presented with an abrupt,
      painless, unilateral visual loss. Thoracic computed tomography disclosed
      mediastinal lymphadenopathy, and evidence from histopathology confirmed
      sarcoidosis. COMMENTS: Corticosteroids alone and with immunosuppressive agents
      failed to suppress the active disease. Alternative therapy of infliximab
      perfusions resulted in disease remission and relative visual improvement, and
      this treatment may warrant further clinical studies.

PMID- 17224963
TI  - Inverse hypopyon as the presenting feature of infectious scleritis in a case of
      tropical pyomyositis.
AB  - CASE REPORT: A 25-year-old man presented with inverse hypopyon due to dense
      inflammatory exudation in the left eye. He was an ascetic with a history of long
      pilgrimages barefoot. Drainage of the pyogenic material with superficial
      exploration revealed localized scleral thinning at 2'o clock. Two days later, a
      thigh abscess was noted, which on ultrasonography showed hypoechoic areas with
      increased muscle mass suggestive of tropical pyomyositis. The culture from
      anterior chamber aspirate grew Staphylococcus aureus, as did 200 mL of pus
      drained from the thigh. His ocular condition improved significantly with high
      dose systemic antibiotics. COMMENTS: To our knowledge, this unusual presentation
      of infectious scleritis and coexistent pyomyositis has not been previously
      reported in the literature.

PMID- 17224964
TI  - Blastoschizomyces capitatus keratitis and melting in a corneal graft.
AB  - CASE REPORT: We present the first case, to our knowledge, of Blastoschizomyces
      capitatus keratitis and melting in a corneal graft. An 80-year-old man was
      treated for a large, severe corneal abscess and melting in the corneal graft of
      his right eye. Medical history was negative for hematologic disorders. Urgent
      penetrating keratoplasty was performed. COMMENTS: Corneal cultures grew B.
      capitatus. Systemic fluconazole and systemic and topical amphotericin B treatment
      were started. Three months after the last operation, no recurrence was observed
      and the graft remained clear. B. capitatus can rarely cause severe keratitis in
      patients even in the absence of hematologic disorders.

PMID- 17224965
TI  - Clinical, histologic, and immunohistochemical evaluation of iris metastases from
      small cell lung carcinoma.
AB  - CASE REPORT: We report the case of a patient with small cell lung carcinoma who
      developed multiple metastases in the iris. The eye was enucleated after failure
      of a conservative approach. The specimen underwent histologic and
      immunohistochemical evaluation that confirmed the diagnosis. COMMENTS: Metastatic
      carcinoma is the most common form of intraocular malignancy, and breast is the
      most prevalent primary location, followed by lung. Small cell lung carcinoma
      constitutes 23.1% of lung neoplasias. It has a significantly worse prognosis than
      non-small cell carcinoma due to its propensity for early and widespread
      dissemination. Uveal metastases involve the choroid more often than the iris and
      ciliary body, probably because the arterial distribution is more abundant in the
      posterior than in the anterior uvea. Iris involvement represents only 9% of the
      metastatic uveal tumours.

PMID- 17224966
TI  - Ocular neovascularization in a patient with Fanconi anemia.
AB  - CASE REPORT: An 11-year-old girl diagnosed with Fanconi anemia was referred to us
      for redness and pain in her right eye. Findings in the right eye included visual
      acuity of counting fingers, neovascular glaucoma, vitreous hemorrhage, optic disc
      neovascularization, and features of peripheral ischemic retinopathy. Findings in
      the left eye included peripheral retinal neovascularization and areas of retinal
      capillary nonperfusion. COMMENTS: Patients with Fanconi anemia may develop ocular
      neovascularization with subsequent severe visual loss due to vitreous hemorrhage
      or neovascular glaucoma. Regular ophthalmic examination, including ophthalmoscopy
      and fluorescein angiography in selected cases, is recommended in such patients.

PMID- 17224967
TI  - Perthes syndrome associated with bilateral optic disc edema.
AB  - CASE REPORT: Perthes syndrome, or traumatic asphyxia syndrome, results from a
      severe crush injury of the thorax. It manifests itself with facial and upper
      chest petechiae, subconjunctival hemorrhages, cervical cyanosis, and occasionally
      neurological symptoms. A patient who had been incarcerated under a block of
      marble presented with severe traumatic asphyxia syndrome complicated by pulmonary
      contusion, fractures of the right clavicle and the 8th and 9th ribs, minimal
      right hemothorax, liver contusion, and bilateral optic disc edema. COMMENTS: To
      our knowledge, we present the first case of Perthes syndrome with bilateral optic
      disc edema.

PMID- 17224968
TI  - Ixodes tick infestation of the eyelid of a child.

PMID- 17224969
TI  - Fourth nerve palsy associated with almost complete absence of the superior
      oblique muscle.

PMID- 17224971
TI  - Epithelial-mesenchymal transition: a potential therapeutic goal for prevention of
      wound fibrosis?

PMID- 17224972
TI  - Parallel asynchronous particle swarm optimization.
AB  - The high computational cost of complex engineering optimization problems has
      motivated the development of parallel optimization algorithms. A recent example
      is the parallel particle swarm optimization (PSO) algorithm, which is valuable
      due to its global search capabilities. Unfortunately, because existing parallel
      implementations are synchronous (PSPSO), they do not make efficient use of
      computational resources when a load imbalance exists. In this study, we introduce
      a parallel asynchronous PSO (PAPSO) algorithm to enhance computational
      efficiency. The performance of the PAPSO algorithm was compared to that of a
      PSPSO algorithm in homogeneous and heterogeneous computing environments for small
      to medium-scale analytical test problems and a medium-scale biomechanical test
      problem. For all problems, the robustness and convergence rate of PAPSO were
      comparable to those of PSPSO. However, the parallel performance of PAPSO was
      significantly better than that of PSPSO for heterogeneous computing environments
      or heterogeneous computational tasks. For example, PAPSO was 3.5 times faster
      than was PSPSO for the biomechanical test problem executed on a heterogeneous
      cluster with 20 processors. Overall, PAPSO exhibits excellent parallel
      performance when a large number of processors (more than about 15) is utilized
      and either (1) heterogeneity exists in the computational task or environment, or
      (2) the computation-to-communication time ratio is relatively small.

PMID- 17224973
TI  - Health and medical informatics education. Proceedings of a special topics
      conference held by the European Federation of Medical Informatics and Working
      Group Education. March 2005. Athens, Greece.

PMID- 17224974
TI  - The WHO eHealth Resolution - eHealth for all by 2015?

PMID- 17224975
TI  - An intelligent data mining model approach for adverse effects of hormone
      replacement therapy.
AB  - OBJECTIVES: A number of controversial studies have been reported on the potential
      risk of breast cancer caused by hormone replacement therapy (HRT). Some studies
      showed a positive relationship between HRT and breast cancer onset, but other
      studies have not confirmed these results. To clarify the contradictory outcomes
      in the relationships between HRT and the onset of breast cancer, we have designed
      an intelligent data mining model (IDM), which is able to find proper prognostic
      factors for cancer onset and provides alternate measures in interpretation of
      outcome of clinical data through hierarchies of attributes. METHODS: Based on the
      selection criteria, we selected 22 sets of random and case-control studies of the
      last 15 years, which identified any involvements of HRT with breast cancer. We
      analyzed the relationship between HRT and breast cancer using an IDM model
      consisting of data mining algorithms and public domain data mining tools.
      Prognostic factors which underline the major etiological dispositions of breast
      cancer were identified. RESULTS: The variables which are closely associated with
      cancer onset to some degree are age 60-69, age at menopause 40-49, parity 0, age
      40-49, and types of menopause oophorectomy. An implementation of IDM model on
      overall pooled data indicated that there is no significant relationship between
      breast cancer onset and HRT. It is suggested that HRT patients with specific
      physiological and pathological conditions related with the higher ranks of
      prognostic factors may have a greater chance to get breast cancer. CONCLUSION:
      The results of this study may guide biomedical research directed at establishing
      the causal relationships between various medications and their complications,
      allowing an accurate assessment of efficacy and side effects of new therapeutic
      treatment in clinical trials without reliance on a large control population.

PMID- 17224976
TI  - sispread: A software to simulate infectious diseases spreading on contact
      networks.
AB  - OBJECTIVES: We present a simulation software which allows studying the dynamics
      of a hypothetic infectious disease within a network of connected people. The
      software is aimed to facilitate the discrimination of stochastic factors
      governing the evolution of an infection in a network. In order to do this it
      provides simple tools to create networks of individuals and to set the
      epidemiological parameters of the outbreaks. METHODS: Three popular models of
      infectious disease can be used (SI, SIS, SIR). The simulated networks are either
      the algorithm-based included ones (scale free, small-world, and random
      homogeneous networks), or provided by third party software. RESULTS: It allows
      the simulation of a single or many outbreaks over a network, or outbreaks over
      multiple networks (with identical properties). Standard outputs are the evolution
      of the prevalence of the disease, on a single outbreak basis or by averaging many
      outbreaks. The user can also obtain customized outputs which address in detail
      different possible epidemiological questions about the spread of an infectious
      agent in a community. CONCLUSIONS: The presented software introduces sources of
      stochasticity present in real epidemics by simulating outbreaks on contact
      networks of individuals. This approach may help to understand the paths followed
      by outbreaks in a given community and to design new strategies for preventing and
      controlling them.

PMID- 17224977
TI  - Designing and redesigning medical telecare services: a forces-oriented model.
AB  - OBJECTIVES: Medical telecare services' designing and redesigning still remains a
      challenging issue since it often depends on how a number of socio-technological
      issues are framed. This work has two key objectives; the former is to
      theoretically analyze the nature of a telecare environment by developing a model
      that reveals potential areas of analysis and the latter is to support designing
      and redesigning medical telecare services by formulating a strategy as well as a
      number of 'state of the art' guidelines. METHODS: We have extended Leavitt's
      diamond to develop a model capable of accurately reflecting the telecare
      environment building dimensions as well as their interactions. This model depends
      on the i) technology, ii) collaborators, iii) tasks, iv) structure, v) social
      forces, and the vi) procedure dimensions. Taking this model as a core element we
      have proposed a service designing and redesigning strategy formulating, in
      parallel, six scalable dimension-oriented guidelines. RESULT: During the two-year
      period (2003-2005) an enormous amount of data was collected (by active
      participating in two EU projects, by conducting semistructured interviews, by
      performing onsite observations as well as by reviewing 78 previous projects) and
      classified, structuring six guidelines. These guidelines can be considered as the
      'state of the art' to support future services' design and redesign. CONCLUSIONS:
      This work considering the telecare environment as a multi-dimensional,
      operational organization has put the focus on accurate telecare services' design
      and redesign. The parameters are not limited, by any means, and are drawn from
      experience of designing services in a variety of telecare domains. The optimal
      parameter combination must be chosen according to the aim of each telecare
      procedure. Further research is needed to determine the minimum parameters to
      support telecare service design.

PMID- 17224978
TI  - AAM-based segmentation for imaging cardiac electrophysiology.
AB  - OBJECTIVES: Activation time (AT) imaging from electrocardiographic (ECG) mapping
      data has been developing for several years. By coupling 4-dimensional volume data
      (3D + time) the electrical sequence can be computed non-invasively. In this paper
      an approach for extracting the ventricular and atrial blood masses for
      structurally normal hearts by using cine-gated short-axis data obtained via
      magnetic resonance imaging (MRI) is introduced. METHODS: The blood masses are
      extracted by employing Active Appearance Models (AAMs). The ventricular blood
      masses are segmented, applying the AAMs after providing apex cordis and base of
      the heart in the volume data, whereas the more complex geometry of the atria
      requires a more specific attempt. On account of this the atrium was divided into
      three divisions of appearance, where the images of the volume data in the related
      divisions have a maximum affinity. The first division reaches from the base of
      the heart to initial visibility of the upper and left lower pulmonary vein. The
      second division up from there to the last occurrence and the third division from
      there to the end of the visibility of the right upper and lower pulmonary vein.
      After extracting the cardiac blood masses the result gets triangulated and
      remeshed for activation time imaging. RESULTS: With this method the cardiac
      models of eight patients were extracted and the AT imaging approach was applied
      to single-beat ECG data of atrial and ventricular depolarization. CONCLUSION: The
      advantage of the proposed AAM approach is that only a few initial parameters have
      to be set. Therefore, the approach can be integrated into a processing pipeline
      that works semi-automatically. The extracted models can be used for further
      investigations.

PMID- 17224980
TI  - Health and medical informatics education.

PMID- 17224979
TI  - The Framingham risk function underestimated absolute coronary heart disease risk
      in Czech men.
AB  - OBJECTIVES: The aim was to validate the Framingham coronary heart disease (CHD)
      risk function with the formula by Wilson et al. (1998) in Czech men. METHODS: The
      validation was performed within the 20-year primary prevention study of
      atherosclerotic risk factors (STULONG) including 1417 middle-aged men from the
      Czech Republic (Prague). A total of 646 men examined in 1979-1988, and followed
      up for ten years, were included into the validation study. The calibration and
      discrimination ability of the Framingham risk function in the Czech population
      were explored. RESULTS: The estimated 10-year risk of CHD by the Framingham risk
      function was 12.8% in 646 men, significantly higher than the observed risk (16.4
      %), p = 0.013. The trend in the 10-year incidence of CHD was significantly
      increasing with quintiles of the estimated risk, p < 0.001. After the
      recalibration of the Framingham risk function, there was an insignificant
      difference between the estimated (18.2%) and observed (16.4%) risks of CHD, p =
      0.320. The Framingham risk function classified men into those with and without
      CHD in the 10-year period with accuracy over 60%. CONCLUSIONS: Unlike some
      validation studies from Western Europe, the Framingham risk function
      significantly underestimated the 10-year CHD risk in the Czech Republic. In
      agreement with these studies, the incidence of CHD was significantly increasing
      across quintiles of the estimated risk.

PMID- 17224981
TI  - Educational challenge of health information systems' interoperability.
AB  - OBJECTIVES: As health care develops from an organization-centered via service
      centered (disease management) towards a person-centered system (favored homecare,
      patient monitoring, body area networks), information systems involved have to be
      semantically interoperable, process-related, decision-supportive, context
      sensitive, user-oriented, and trustworthy. METHODS: The aforementioned paradigm
      shift requires highly flexible solutions based on knowledge concepts, provided by
      a service-oriented and model-driven approach. RESULTS: Information systems'
      design, implementation and maintenance have to be realized based on formal
      grammar. This is true for all considered aspects and views of the system and its
      components, using metalanguages and reflecting all domains touched. CONCLUSIONS:
      For meeting the challenge, involvement of, and close collaboration between,
      experts from different domains as well as knowledge and tooling regarding formal
      modeling and model interchange are required.

PMID- 17224982
TI  - An educational intervention, involving feedback of routinely collected computer
      data, to improve cardiovascular disease management in UK primary care.
AB  - OBJECTIVES: To report the lessons learned from eight years of feeding back
      routinely collected cardiovascular data in an educational context METHODS: There
      are distinct educational and technical components. The educational component
      provides peer-led learning opportunities based on comparative analysis of quality
      of care, as represented in computer records. The technical part ensures that
      relevant evidence-based audit criteria are identified; an appropriate dataset is
      extracted and processed to facilitate quality improvement. Anonymised data are
      used to provide inter-practice comparisons, with lists of identifiable patients
      who need interventions left in individual practices. RESULTS: The progressive
      improvement in cholesterol management in ischaemic heart disease (IHD) is used as
      an exemplar of the changes achieved. Over three iterations of the cardiovascular
      programme the standardised prevalence of IHD recorded in GP computer systems rose
      from 3.8% to 4.0%. Cholesterol recording rose from 47.6% to 89.0%; and the mean
      cholesterol level fell from 5.18 to 4.67 mmol/L; while statin prescribing rose
      from 46% to 57% to 68%. The atrial fibrillation, heart failure and renal
      programmes (more people with chronic kidney disease go on to die from
      cardiovascular cause than from end-stage renal disease) are used to demonstrate
      the range of cardiovascular interventions amenable to this approach. CONCLUSIONS:
      Technical progress has meant that larger datasets can be extracted and processed.
      Feedback of routinely collected data in an educational context is acceptable to
      practitioners and results in quality improvement. Further research is needed to
      assess its utility as a strategy and cost-effectiveness compared with other
      methods.

PMID- 17224983
TI  - Interdisciplinary innovations in biomedical and health informatics graduate
      education.
AB  - OBJECTIVES: Biomedical and health informatics (BHI) is a rapidly growing domain
      that relies on the active collaboration with diverse disciplines and professions.
      Educational initiatives in BHI need to prepare students with skills and
      competencies that will allow them to function within and even facilitate
      interdisciplinary teams (IDT). This paper describes an interdisciplinary
      educational approach introduced into a BHI graduate curriculum that aims to
      prepare informatics researchers to lead IDT research. METHODS: A case study of
      the "gerontechnology" research track is presented which highlights how the
      curriculum fosters collaboration with and understanding of the disciplines of
      Nursing, Engineering, Computer Science, and Health Administration.
      Gerontechnology is a new interdisciplinary field that focuses on the use of
      technology to support aging. Its aim is to explore innovative ways to use
      information technology and develop systems that support independency and increase
      quality of life for senior citizens. As a result of a large research group that
      explores "smart home" technologies and the use of information technology, we
      integrated this new domain into the curriculum providing a platform for computer
      scientists, engineers, nurses and physicians to explore challenges and
      opportunities with our informatics students and faculty. RESULTS: The
      interdisciplinary educational model provides an opportunity for health
      informatics students to acquire the skills for communication and collaboration
      with other disciplines. Numerous graduate and postgraduate students have already
      participated in this initiative. The evaluation model of this approach is
      presented. CONCLUSION: Interdisciplinary educational models are required for
      health informatics graduate education. Such models need to be innovative and
      reflect the needs and trends in the domains of health care and information
      technology.

PMID- 17224984
TI  - Challenges and perspectives of computer-assisted instruction in medical
      education: lessons learned from seven years of experience with the CAMPUS system.
AB  - OBJECTIVES: In this paper we discuss solutions to the problem that medical
      teachers and students do not use modern computer-assisted instruction systems in
      medical education as much as expected by their developers. METHODS: As an example
      for a modern problem-based CAI system we introduce the CAMPUS shell system for
      case-based training in medicine. RESULTS: CAMPUS has received several awards and
      positive evaluation results. Nevertheless, the usage of such systems in courses
      and for self-study could be increased. CONCLUSIONS: Curricular integration of CAI
      as well as further improvements on existing CAI systems to increase the usage in
      medical education is essential.

PMID- 17224985
TI  - Evaluation of a course on patient records.
AB  - OBJECTIVES: To determine whether self-directed learning about (electronic)
      patient records during a PBL (problem-based learning) block, dealing with the
      content of disciplines concerned with the diagnosis and therapy of diseases of
      the abdomen, increased the knowledge of the students with respect to the patient
      records. METHODS: At the beginning and at the end of the ten-week block the same
      questionnaire was offered to the students (180). Cohen's d for effect size was
      used to determine the increase in knowledge. RESULTS: For those students that
      answered the questionnaire twice (53), a Cohen's d of 0.94 was obtained.
      CONCLUSIONS: The knowledge of the students concerning the advantages and
      limitations of (electronic) patient records increased significantly. The
      corresponding effect size was large.

PMID- 17224986
TI  - On educating about medical data management - the other side of the electronic
      health record.
AB  - OBJECTIVES: To summarize background, challenges, objectives, and methods for the
      usability of patient data, in particular with respect to their multiple use, and
      to point out how to lecture medical data management. METHODS: Analyzing the
      literature, providing an example based on Simpson's paradox and summarizing
      research and education in the field of medical data management, respectively
      health information management (in German: Medizinische Dokumentation). RESULTS:
      For the multiple use of patient data, three main categories of use can be
      identified: patient-oriented (or casuistic) analysis, patient-group reporting,
      and analysis for clinical studies. A so-called documentation protocol, related to
      study plans in clinical trials, supports the multiple use of data from the
      electronic health record in order to obtain valid, interpretable results.
      Lectures on medical data management may contain modules on introduction, basic
      concepts of clinical data management and coding systems, important medical coding
      systems (e.g. ICD, SNOMED, TNM, UMLS), typical medical documentation systems
      (e.g. on patient records, clinical and epidemiological registers), utilization of
      clinical data management systems, planning of medical coding systems and of
      clinical data management systems, hospital information systems and the electronic
      patient record, and on data management in clinical studies. CONCLUSION:
      Usability, the ultimate goal of recording and managing patient data, requires,
      besides technical considerations, in addition appropriate methodology on medical
      data management, especially if data is intended to be used for multiple purposes,
      e.g. for patient care and quality management and clinical research. Medical data
      management should be taught in health and biomedical informatics programs.

PMID- 17224987
TI  - The full spectrum of biomedical informatics education at Oregon Health & Science
      University.
AB  - OBJECTIVES: The growing use of health information technology in operational
      settings, along with the maturation of the discipline of biomedical informatics,
      requires reorganization of educational programs in the field. The objective of
      this paper is to provide a context and description of the biomedical informatics
      education program at Oregon Health & Science University. METHODS: The details of
      the program are provided. RESULTS: The paper describes the overall program and
      its component curricula. CONCLUSIONS: OHSU has developed a program that caters to
      the full spectrum of those who will work in the field, allowing education
      tailored to their career goals and needs. The maturation of Internet technologies
      also allow most aspects of the program to be delivered on-line. The informatics
      field must step up to the challenge of educating the best workforce to achieve
      our goals for the optimal use of HIT.

PMID- 17224988
TI  - Selected eHealth applications in Cyprus from the training perspective.
AB  - OBJECTIVES: In this paper a review of selected eHealth applications in Cyprus is
      presented linked with their success or failure based on their training
      activities. METHODS: The eHealth systems presented and their training activities
      include an update of the health information system (HIS) in the public hospitals,
      a medical system for emergency telemedicine (AMBULANCE and EMERGENCY-112
      projects), a home monitoring system for cancer patients (DITIS), a satellite
      based network in healthcare applications (EMISPHER and HEALTHWARE projects), and
      the training activities of the Cyprus Society of Medical Informatics. Different
      methodologies for training were used ranging from classical approaches like train
      the trainers, using demo cases followed by personal training, group training, and
      workshops, to more recent methodologies based on eLearning sessions including
      teleconsultations. RESULTS: The training was carried out successfully in all
      cases. However, not all eHealth systems were put into practice successfully,
      mainly for reasons not related to training. CONCLUSIONS: It is anticipated that
      this paper will promote the importance of these applications and their training
      activities as well as help in the spin off of others thus enabling the offering
      of a better service to the citizen.

PMID- 17224989
TI  - Implementation and evaluation of the MSc course in health informatics in Greece.
AB  - OBJECTIVES: Health informatics is a well established and important multi
      disciplinary and inter-disciplinary field that not only involves informatics but
      also medicine, nursing, engineering, biology and other-related subjects. The
      program has been organized on the basis of an inter-university approach with the
      participation of five Greek universities. The paper aims at providing a current
      description of the academic program and a preliminary evaluation of the
      implementation phase. METHODS: The paper presents a case study of a curriculum
      implementation from the phase of curriculum development to the phase of
      implementation and evaluation. Due to the interdisciplinary character of the
      course appropriate procedures were undertaken to ensure that mixed backgrounds
      can assimilate the broad spectrum of the teaching material taught. In the first
      stages of the implementation international students mainly from Europe attended
      the course. In addition, local graduates provided an extra dimension to the multi
      layered difficulties and challenges of such a course implementation. RESULTS: The
      students registered in the course were from different backgrounds and
      disciplines. They were mainly from health sciences and engineering schools. The
      interdisciplinary arrangement of the course facilitated the proper exchange of
      thoughts, skills, and knowledge among and between students and teachers.
      CONCLUSIONS: The postgraduate course in health informatics at the University of
      Athens has now been running for more than fifteen consecutive years and is one of
      the first and longest standing courses in Europe. Continuous evaluation and
      adaptation is required to fit within the changing and evolving amazing field of
      biomedical and health informatics.

PMID- 17224990
TI  - PCR identification of Mycobacterium tuberculosis complex in a clinical sample
      from a patient with symptoms of tuberculous spondylodiscitis.
AB  - A 42-year-old male complaining of thoracic spine pain was admitted to the
      hospital for evaluation. An X-ray and computer tomography of the thoracic spine
      showed spondylodiscitis of the L3 lumbar and L2-L3 intervertebral disk. The
      tuberculin skin test (PPD) was strongly positive. A radioscopy-guided fine needle
      aspirate of the affected area was cultured but did not reveal the cause of the
      disease. Two biopsy attempts failed to reveal the cause of the disease by
      culturing or by acid-fast-resistant staining (Ziehl Neelsen) of the specimens. A
      third biopsy also failed to detect the infectious agent by using microbiological
      procedures, but revealed the presence of a 245-bp amplicon characteristic of the
      Mycobacterium tuberculosis complex after PCR of the sample. The result
      demonstrates the efficacy of PCR for the identification of M. tuberculosis in
      situations in which conventional diagnosis by culturing techniques or direct
      microscopy is unable to detect the microorganism. Following this result the
      patient was treated with the antituberculous cocktail composed by rifampicin,
      pirazinamide and isoniazid during a six-month period. At the end of the treatment
      the dorsalgia symptoms had disappeared.

PMID- 17224991
TI  - A carbohydrate-based mechanism of species recognition in sea urchin
      fertilization.
AB  - In the present review, we describe a systematic study of the sulfated
      polysaccharides from marine invertebrates, which led to the discovery of a
      carbohydrate-based mechanism of sperm-egg recognition during sea urchin
      fertilization. We have described unique polymers present in these organisms,
      especially sulfated fucose-rich compounds found in the egg jelly coat of sea
      urchins. The polysaccharides have simple, linear structures consisting of
      repeating units of oligosaccharides. They differ among the various species of sea
      urchins in specific patterns of sulfation and/or position of the glycosidic
      linkage within their repeating units. These polysaccharides show species
      specificity in inducing the acrosome reaction in sea urchin sperm, providing a
      clear-cut example of a signal transduction event regulated by sulfated
      polysaccharides. This distinct carbohydrate-mediated mechanism of sperm-egg
      recognition coexists with the bindin-protein system. Possibly, the genes involved
      in the biosynthesis of these sulfated fucans did not evolve in concordance with
      evolutionary distance but underwent a dramatic change near the tip of the
      Strongylocentrotid tree. Overall, we established a direct causal link between the
      molecular structure of a sulfated polysaccharide and a cellular physiological
      event - the induction of the sperm acrosome reaction in sea urchins. Small
      structural changes modulate an entire system of sperm-egg recognition and species
      specific fertilization in sea urchins. We demonstrated that sulfated
      polysaccharides - in addition to their known function in cell proliferation,
      development, coagulation, and viral infection - mediate fertilization, and
      respond to evolutionary mechanisms that lead to species diversity.

PMID- 17224992
TI  - Erythrocyte phosphoglucomutase activity of bipolar I patients currently using
      lithium or carbamazepine.
AB  - Lithium has been used for the last five decades to treat bipolar disorder, but
      the molecular basis of its therapeutic effect is unknown. Phosphoglucomutase is a
      key enzyme in the metabolism of glycogen. In yeast, rabbit and human HEK293
      cells, it is inhibited by lithium in the therapeutic concentration range. We
      measured the phosphoglucomutase activity in erythrocytes and the inhibitor
      constant for lithium in a population of healthy subjects and compared them to
      those of bipolar patients treated with lithium or carbamazepine. The specific
      activity of phosphoglucomutase measured in vitro in erythrocytes from control
      subjects presented a normal distribution, with the difference between the lowest
      and the highest activity being approximately 2-fold (0.53-1.10 nmol mg Hb-1 min
      1). Comparison of phosphoglucomutase activity in untreated bipolar patients and
      control subjects showed no significant difference, whereas comparison between
      bipolar patients treated with carbamazepine or lithium revealed significantly
      lower mean values in patients treated with carbamazepine (747.3 +/- 27.6 vs 879.5
      +/- 35.9 pmol mg Hb-1 min-1, respectively). When we studied the concentration of
      lithium needed to inhibit phosphoglucomutase activity by 50%, a bimodal
      distribution among the population tested was obtained. The concentration of LiCl
      needed to inhibit phosphoglucomutase activity by 50% was 0.35 to 1.8 mM in one
      group of subjects and in the other it was 3 to 4 mM. These results suggest that
      phosphoglucomutase activity may be significant in patients with bipolar disorder
      treated with lithium and carbamazepine.

PMID- 17224993
TI  - Down-regulation of the cardiac sarcoplasmic reticulum ryanodine channel in
      severely food-restricted rats.
AB  - We have shown that myocardial dysfunction induced by food restriction is related
      to calcium handling. Although cardiac function is depressed in food-restricted
      animals, there is limited information about the molecular mechanisms that lead to
      this abnormality. The present study evaluated the effects of food restriction on
      calcium cycling, focusing on sarcoplasmic Ca2+-ATPase (SERCA2), phospholamban
      (PLB), and ryanodine channel (RYR2) mRNA expressions in rat myocardium. Male
      Wistar-Kyoto rats, 60 days old, were submitted to ad libitum feeding (control
      rats) or 50% diet restriction for 90 days. The levels of left ventricle SERCA2,
      PLB, and RYR2 were measured using semi-quantitative RT-PCR. Body and ventricular
      weights were reduced in 50% food-restricted animals. RYR2 mRNA was significantly
      decreased in the left ventricle of the food-restricted group (control = 5.92 +/-
      0.48 vs food-restricted group = 4.84 +/- 0.33, P < 0.01). The levels of SERCA2
      and PLB mRNA were similar between groups (control = 8.38 +/- 0.44 vs food
      restricted group = 7.96 +/- 0.45, and control = 1.52 +/- 0.06 vs food-restricted
      group = 1.53 +/- 0.10, respectively). Down-regulation of RYR2 mRNA expressions
      suggests that chronic food restriction promotes abnormalities in sarcoplasmic
      reticulum Ca2+ release.

PMID- 17224994
TI  - Rapid test for the evaluation of the activity of the prodrug
      hydroxymethylnitrofurazone in the processing of Trypanosoma cruzi messenger RNAs.
AB  - No fully effective treatment has been developed since the discovery of Chagas'
      disease by Carlos Chagas in 1909. Since drug-resistant Trypanosoma cruzi strains
      are occurring and the current therapy is effectiveness in the acute phase but
      with various adverse side effects, more studies are needed to characterize the
      susceptibility of T. cruzi to new drugs. Many natural and/or synthetic substances
      showing trypanocidal activity have been used, even though they are not likely to
      be turned into clinically approved drugs. Originally, drug screening was
      performed using natural products, with only limited knowledge of the molecular
      mechanism involved in the development of diseases. Trans-splicing, which is
      unusual RNA processing reaction and occurs in nematodes and trypanosomes, implies
      the processing of polycistronic transcription units into individual mRNAs; a
      short transcript spliced leader (SL RNA) is trans-spliced to the acceptor pre
      mRNA, giving origin to the mature mRNA. In the present study, permeable cells of
      T. cruzi epimastigote forms (Y, BOL and NCS strains) were treated to evaluate the
      interference of two drugs (hydroxymethylnitrofurazone - NFOH-121 and
      nitrofurazone) in the trans-splicing reaction using silver-stained PAGE analysis.
      Both drugs induced a significant reduction in RNA processing at concentrations
      from 5 to 12.5 microM. These data agreed with the biological findings, since the
      number of parasites decreased, especially with NFOH-121. This proposed
      methodology allows a rapid and cost-effective screening strategy for detecting
      drug interference in the trans-splicing mechanism of T. cruzi.

PMID- 17224995
TI  - Beneficial effect of recombinant human growth hormone on the intestinal mucosa
      barrier of septic rats.
AB  - The objective of the present study was to investigate the effects of recombinant
      human growth hormone (rhGH) on the intestinal mucosa barrier of septic rats and
      explore its possible mechanism. Female Sprague-Dawley rats were randomized into
      three groups: control, Escherichia coli-induced sepsis (S) and treatment (T)
      groups. Groups S and T were subdivided into subgroups 1d and 3d, respectively.
      Expression of liver insulin-like growth factor-1 (IGF-1) mRNA, Bcl-2 and Bax
      protein levels and the intestinal Bax/Bcl-2 ratio, and plasma GH and IGF-1 levels
      were determined. Histological examination of the intestine was performed and
      bacterial translocation was determined. rhGH significantly attenuated intestinal
      mucosal injuries and bacterial translocation in septic rats, markedly decreased
      Bax protein levels, inhibited the decrease of Bcl-2 protein expression and
      maintained the Bax/Bcl-2 ratio in the intestine. rhGH given after sepsis
      significantly improved levels of plasma GH (T1d: 1.28 +/- 0.24; T3d: 2.14 +/-
      0.48 microg/L vs S1d: 0.74 +/- 0.12; S3d: 0.60 +/- 0.18 microg/L; P < 0.05) and
      IGF-1 (T1d: 168.94 +/- 65.67; T3d: 201.56 +/- 64.98 microg/L vs S1d: 116.72 +/-
      13.96; S3d: 107.50 +/- 23.53 microg/L; P < 0.05) and expression of liver IGF-1
      mRNA (T1d: 0.98 +/- 0.20; T3d: 1.76 +/- 0.17 vs S1d: 0.38 +/- 0.09; S3d: 0.46 +/-
      0.10; P < 0.05). These findings indicate that treatment with rhGH had beneficial
      effects on the maintenance of the integrity of the intestinal mucosa barrier in
      septic rats.

PMID- 17224997
TI  - Mesenchymal stem cells from patients with chronic myeloid leukemia do not express
      BCR-ABL and have absence of chimerism after allogeneic bone marrow transplant.
AB  - Bone marrow is a heterogeneous cell population which includes hematopoietic and
      mesenchymal progenitor cells. Dysregulated hematopoiesis occurs in chronic
      myelogenous leukemia (CML), being caused at least in part by abnormalities in the
      hematopoietic progenitors. However, the role of mesenchymal stem cells (MSCs) in
      CML has not been well characterized. The objectives of the present study were to
      observe the biological characteristics of MSCs from CML patients and to determine
      if MSCs originate in part from donors in CML patients after bone marrow
      transplantation (BMT). We analyzed MSCs from 5 untreated patients and from 3 CML
      patients after sex-mismatched allogeneic BMT. Flow cytometry analysis revealed
      the typical MSC phenotype and in vitro assays showed ability to differentiate
      into adipocytes and osteoblasts. Moreover, although some RT-PCR data were
      contradictory, combined fluorescence in situ hybridization analysis showed that
      MSCs from CML patients do not express the bcr-abl gene. Regarding MSCs of donor
      origin, although it is possible to detect Y target sequence by nested PCR, the
      low frequency (0.14 and 0.34%) of XY cells in 2 MSC CML patients by fluorescence
      in situ hybridization analysis suggests the presence of contaminant hematopoietic
      cells and the absence of host-derived MSCs in CML patients. Therefore, we
      conclude that MSCs from CML patients express the typical MSC phenotype, can
      differentiate into osteogenic and adipogenic lineages and do not express the bcr
      abl gene. MSCs cannot be found in recipients 12 to 20 months after BMT. The
      influence of MSCs on the dysregulation of hematopoiesis in CML patients deserves
      further investigation.

PMID- 17224996
TI  - Apolipoprotein E polymorphism in Brazilian dyslipidemic individuals: Ouro Preto
      study.
AB  - The influence of apolipoprotein E alleles and genotypes on plasma lipid levels
      was determined in 185 individuals of mixed ethnicity living in Ouro Preto,
      Brazil. DNA was obtained from blood samples and the genotypes were determined by
      an RFLP-PCR procedure. The *3 allele was the most frequent (72%), followed by *4
      (20%) and *2 (8%); *4 frequency was higher and *2 frequency was lower in the
      dyslipidemic group than in the normal control group. The *2 carriers presented
      lower LDL and total cholesterol levels compared to the *3 and *4 carriers. All
      six expected genotypes were observed in the individuals genotyped: E2/2 (2.1%),
      E4/4 (2.7%), E2/4 (3.7%), E2/3 (8.0%), E3/3 (53.3%), E3/4 (29.9%); no difference
      in genotype frequencies was found between the normal and dyslipidemic groups.
      Compared with *2, the presence of *3 increases more than two times the risk for
      dyslipidemia (OR = 2.31; P = 0.025; 95% CI = 1.06-5.06) and the presence of *4
      increases it three times (OR = 3.31; P = 0.006; 95% CI = 1.36-8.04). The only
      significant effect of genotype was an increased risk for dyslipidemia in the *4
      genotype carriers (E3/4 + E4/4) compared with the *2 genotype carriers (E2/2 +
      E2/3) with OR = 3.69 (95% CI = 1.25-10.88). The present study indicates that in
      the Ouro Preto admixed population the presence of APOE *2 can confer a protective
      effect, whereas the presence of APOE *4 implies an enhanced risk for
      dyslipidemia.

PMID- 17224998
TI  - Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin
      neutralization assay and a modified toxin-binding inhibition test.
AB  - A method for the screening of tetanus and diphtheria antibodies in serum using
      anatoxin (inactivated toxin) instead of toxin was developed as an alternative to
      the in vivo toxin neutralization assay based on the toxin-binding inhibition test
      (TOBI test). In this study, the serum titers (values between 1.0 and 19.5 IU)
      measured by a modified TOBI test (Modi-TOBI test) and toxin neutralization assays
      were correlated (P < 0.0001). Titers of tetanus or diphtheria antibodies were
      evaluated in serum samples from guinea pigs immunized with tetanus toxoid,
      diphtheria-tetanus or triple vaccine. For the Modi-TOBI test, after blocking the
      microtiter plates, standard tetanus or diphtheria antitoxin and different
      concentrations of guinea pig sera were incubated with the respective anatoxin.
      Twelve hours later, these samples were transferred to a plate previously coated
      with tetanus or diphtheria antitoxin to bind the remaining anatoxin. The anatoxin
      was then detected using a peroxidase-labeled tetanus or diphtheria antitoxin.
      Serum titers were calculated using a linear regression plot of the results for
      the corresponding standard antitoxin. For the toxin neutralization assay,
      L+/10/50 doses of either toxin combined with different concentrations of serum
      samples were inoculated into mice for anti-tetanus detection, or in guinea pigs
      for anti-diphtheria detection. Both assays were suitable for determining wide
      ranges of antitoxin levels. The linear regression plots showed high correlation
      coefficients for tetanus (r(2) = 0.95, P < 0.0001) and for diphtheria (r(2) =
      0.93, P < 0.0001) between the in vitro and the in vivo assays. The standardized
      method is appropriate for evaluating titers of neutralizing antibodies, thus
      permitting the in vitro control of serum antitoxin levels.

PMID- 17224999
TI  - Effect of oral ingestion of an extract of the herb Uncaria tomentosa on the
      biodistribution of sodium pertechnetate in rats.
AB  - The aim of the present study was to determine the effect of the oral ingestion of
      an extract of the herb Uncaria tomentosa (cat's claw) on the biodistribution of
      the radiobiocomplex sodium pertechnetate (Na99mTcO4) in rats. The animals (male
      Wistar rats, 2 months old, 180-220 g), were treated (1 mL) with an U. tomentosa
      extract (32 mg/mL, N = 5) or 0.9% NaCl solution (control, N = 5) for 7 days.
      After this period, Na99mTcO4 (3.7 MBq, 0.3 mL) was injected through the ocular
      plexus and after 10 min the rats were killed, the organs isolated and counted in
      a well-gamma counter. A significant (P < 0.05) alteration in Na99mTcO4 uptake i)
      from 0.57 +/- 0.008 to 0.39 +/- 0.06 %ATI/organ (P < 0.05) and from 0.57 +/- 0.17
      to 0.39 +/- 0.14 %ATI/g (P < 0.05) was observed in the heart, ii) from 0.07 +/-
      0.02 to 0.19 +/- 0.07 %ATI/g in the pancreas, and iii) from 0.07 +/- 0.01 to 0.18
      +/- 0.07 %ATI/g (P < 0.05) in muscle after treatment with this extract. Although
      these results were obtained with animals, caution is advisable in the
      interpretation of the nuclear medicine examination when the patient is using this
      herb. This finding is probably an example of drug interaction with a
      radiopharmaceutical, a fact that could lead to misdiagnosis of the examination in
      clinical practice with unexpected consequences for the patient.

PMID- 17225000
TI  - Modifications of the sympathetic skin response in workers chronically exposed to
      lead.
AB  - The long-term effects of low-level lead intoxication are not known. The
      sympathetic skin response (SSR) was evaluated in a group of 60 former workers of
      a primary lead smelter, located in Santo Amaro, BA, Brazil. The individuals
      participating in the study were submitted to a clinical-epidemiological
      evaluation including questions related to potential risk factors for
      intoxication, complaints related to peripheral nervous system (PNS) involvement,
      neurological clinical examination, and also to electromyography and nerve
      conduction studies and SSR evaluation. The sample consisted of 57 men and 3 women
      aged 34 to 69 years (mean +/- SD: 46.8 +/- 6.9). The neurophysiologic evaluation
      showed the presence of lumbosacral radiculopathy in one of the individuals
      (1.7%), axonal sensorimotor polyneuropathy in 2 (3.3%), and carpal tunnel
      syndrome in 6 (10%). SSR was abnormal or absent in 12 cases, representing 20% of
      the sample. More than half of the subjects (53.3%) reported a history of acute
      abdominal pain requiring hospitalization during the period of work at the plant.
      A history of acute palsy of radial and peroneal nerves was reported by about 16.7
      and 8.3% of the individuals, respectively. Mean SSR amplitude did not differ
      significantly between patients presenting or not the various characteristics in
      the current neurological situation, except for diaphoresis. The results suggest
      that chronic lead intoxication induces PNS damage, particularly affecting
      unmyelinated small fibers. Further systematic study is needed to more precisely
      define the role of lead in inducing PNS injury.

PMID- 17225002
TI  - A new model for the population pharmacokinetics of didanosine in healthy
      subjects.
AB  - Didanosine (ddI) is a component of highly active antiretroviral therapy drug
      combinations, used especially in resource-limited settings and in zidovudine
      resistant patients. The population pharmacokinetics of ddI was evaluated in 48
      healthy volunteers enrolled in two bioequivalence studies. These data, along with
      a set of co-variates, were the subject of a nonlinear mixed-effect modeling
      analysis using the NONMEM program. A two-compartment model with first order
      absorption (ADVAN3 TRANS3) was fitted to the serum ddI concentration data. Final
      pharmacokinetic parameters, expressed as functions of the co-variates gender and
      creatinine clearance (CL CR), were: oral clearance (CL = 55.1 + 240 x CL CR +
      16.6 L/h for males and CL = 55.1 + 240 x CL CR for females), central volume (V2 =
      9.8 L), intercompartmental clearance (Q = 40.9 L/h), peripheral volume (V3 = 62.7
      + 22.9 L for males and V3 = 62.7 L for females), absorption rate constant (Ka =
      1.51/h), and dissolution time of the tablet (D = 0.43 h). The intraindividual
      (residual) variability expressed as coefficient of variation was 13.0%, whereas
      the interindividual variability of CL, Q, V3, Ka, and D was 20.1, 75.8, 20.6,
      18.9, and 38.2%, respectively. The relatively high (>30%) interindividual
      variability for some of these parameters, observed under the controlled
      experimental settings of bioequivalence trials in healthy volunteers, may result
      from genetic variability of the processes involved in ddI absorption and
      disposition.

PMID- 17225001
TI  - Neuroprotective effect of ketamine/xylazine on two rat models of Parkinson's
      disease.
AB  - There is a great concern in the literature for the development of neuroprotectant
      drugs to treat Parkinson's disease. Since anesthetic drugs have hyperpolarizing
      properties, they can possibly act as neuroprotectants. In the present study, we
      have investigated the neuroprotective effect of a mixture of ketamine (85 mg/kg)
      and xylazine (3 mg/kg) (K/X) on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP) or 6-hydroxydopamine (6-OHDA) rat models of Parkinson's disease. The
      bilateral infusion of MPTP (100 microg/side) or 6-OHDA (10 microg/side) into the
      substantia nigra pars compacta of adult male Wistar rats under thiopental
      anesthesia caused a modest (~67%) or severe (~91%) loss of tyrosine hydroxylase
      immunostained cells, respectively. On the other hand, an apparent neuroprotective
      effect was observed when the rats were anesthetized with K/X, infused 5 min
      before surgery. This treatment caused loss of only 33% of the nigral tyrosine
      hydroxylase-immunostained cells due to the MPTP infusion and 51% due to the 6
      OHDA infusion. This neuroprotective effect of K/X was also suggested by a less
      severe reduction of striatal dopamine levels in animals treated with these
      neurotoxins. In the working memory version of the Morris water maze task, both
      MPTP- and 6-OHDA-lesioned animals spent nearly 10 s longer to find the hidden
      platform in the groups where the neurotoxins were infused under thiopental
      anesthesia, compared to control animals. This amnestic effect was not observed in
      rats infused with the neurotoxins under K/X anesthesia. These results suggest
      that drugs with a pharmacological profile similar to that of K/X may be useful to
      delay the progression of Parkinson's disease.

PMID- 17225004
TI  - Comparison of etoricoxib and indomethacin for the treatment of experimental
      periodontitis in rats.
AB  - We investigated the effect of etoricoxib, a selective cyclooxygenase-2 inhibitor,
      and indomethacin, a non-selective cyclooxygenase inhibitor, on experimental
      periodontitis, and compared their gastrointestinal side effects. A ligature was
      placed around the second upper left molars of female Wistar rats (160 to 200 g).
      Animals (6 per group) were treated daily with oral doses of 3 or 9 mg/kg
      etoricoxib, 5 mg/kg indomethacin, or 0.2 mL saline, starting 5 days after the
      induction of periodontitis, when bone resorption was detected, until the
      sacrifice on the 11th day. The weight and survival rate were monitored. Alveolar
      bone loss (ABL) was measured as the sum of distances between the cusp tips and
      the alveolar bone. The gastric mucosa was examined macroscopically and the
      periodontium and gastric and intestinal mucosa were examined by histopathology.
      The ongoing ABL was significantly inhibited (P < 0.05) by 3 and 9 mg/kg
      etoricoxib and by indomethacin: control = 4.08 +/- 0.47 mm; etoricoxib (3 mg/kg)
      = 1.89 +/- 0.26 mm; etoricoxib (9 mg/kg) = 1.02 +/- 0.14 mm; indomethacin = 0.64
      +/- 0.15 mm. Histopathology of periodontium showed that etoricoxib and
      indomethacin reduced inflammatory cell infiltration, ABL, and cementum and
      collagen fiber destruction. Macroscopic and histopathological analysis of gastric
      and intestinal mucosa demonstrated that etoricoxib induces less damage than
      indomethacin. Animals that received indomethacin presented weight loss starting
      on the 7th day, and higher mortality rate (58.3%) compared to etoricoxib (0%).
      Treatment with etoricoxib, even starting when ABL is detected, reduces
      inflammation and cementum and bone resorption, with fewer gastrointestinal side
      effects.

PMID- 17225003
TI  - Pharmacological study of anti-allergic activity of Syzygium cumini (L.) Skeels.
AB  - Myrtaceae is a plant family widely used in folk medicine and Syzygium and Eugenia
      are among the most important genera. We investigated the anti-allergic properties
      of an aqueous leaf extract of Syzygium cumini (L.) Skeels (SC). HPLC analysis
      revealed that hydrolyzable tannins and flavonoids are the major components of the
      extract. Oral administration of SC (25-100 mg/kg) in Swiss mice (20-25 g; N =
      7/group) inhibited paw edema induced by compound 48/80 (50% inhibition, 100
      mg/kg; P <or= 0.05) and, to a lesser extent, the allergic paw edema (23%
      inhibition, 100 mg/kg; P <or= 0.05). SC treatment also inhibited the edema
      induced by histamine (58% inhibition; P <or= 0.05) and 5-HT (52% inhibition; P
      <or= 0.05) but had no effect on platelet-aggregating factor-induced paw edema. SC
      prevented mast cell degranulation and the consequent histamine release in Wistar
      rat (180-200 g; N = 7/group) peritoneal mast cells (50% inhibition, 1 microg/mL;
      P <or= 0.05) induced by compound 48/80. Pre-treatment of BALB/c mice (18-20 g; N
      = 7/group) with 100 mg/kg of the extract significantly inhibited eosinophil
      accumulation in allergic pleurisy (from 7.662 +/- 1.524 to 1.89 +/- 0.336 x
      10(6)/cavity; P <= 0.001). This effect was related to the inhibition of IL-5
      (from 70.9 +/- 25.2 to 12.05 +/- 7.165 pg/mL) and CCL11/eotaxin levels (from 60.4
      +/- 8.54 to 32.8 +/- 8.4 ng/mL) in pleural lavage fluid, using ELISA. These
      findings demonstrate an anti-allergic effect of SC, and indicate that its anti
      edematogenic effect is due to the inhibition of mast cell degranulation and of
      histamine and serotonin effects, whereas the inhibition of eosinophil
      accumulation in the allergic pleurisy model is probably due to an impairment of
      CCL11/eotaxin and IL-5 production.

PMID- 17225005
TI  - Antinociceptive properties in mice of a lectin isolated from the marine alga
      Amansia multifida Lamouroux.
AB  - The antinociceptive effects of a lectin (LEC) isolated from the marine alga
      Amansia multifida were determined in Swiss mice. The LEC (1, 5, and 10 mg/kg)
      inhibited acetic acid-induced abdominal writhings in a dose-dependent manner
      after intraperitoneal or oral administration. A partial but significant
      inhibition of writhings was observed after the combination of LEC (10 mg/kg) with
      avidin (1 mg/kg), a potent inhibitor of the hemmaglutinant activity of the
      lectin. However, total writhing inhibition was demonstrable in the group of mice
      treated with LEC plus mannose (1 mg/kg), as compared to LEC alone or to control
      groups. Furthermore, avidin and mainly mannose also play a role in
      antinociception, somehow facilitating the interaction of LEC with its active cell
      sites. In the formalin test, although both phases of the response were
      significantly inhibited, the effect of LEC was predominant during phase 2,
      causing inhibition of licking time that ranged from 48 to 88% after oral (5 and
      10 mg/kg) and intraperitoneal (1 to 5 mg/kg) administration. As is the case with
      morphine, the effect of LEC (2 mg/kg) was reversed by naloxone (2 mg/kg),
      indicating the involvement of the opioid system. LEC was also effective in the
      hot-plate test, producing inhibitory responses to the thermal stimulus, and its
      effects were blocked by naloxone. In the pentobarbital-induced sleeping time,
      although LEC did not alter the onset of sleep significantly, it increased the
      time of sleep within the same dose range compared to control. These results show
      that LEC presents antinociceptive effects of both central and peripheral origin,
      possibly involving the participation of the opioid system.

PMID- 17225006
TI  - Effect of age and gender on sweat lactate and ammonia concentrations during
      exercise in the heat.
AB  - The dependence of sweat composition and acidity on sweating rate (SR) suggests
      that the lower SR in children compared to adults may be accompanied by a higher
      level of sweat lactate (Lac-) and ammonia (NH3) and a lower sweat pH. Four groups
      (15 girls, 18 boys, 8 women, 8 men) cycled in the heat (42 degrees C, 20%
      relative humidity) at 50% VO2max for two 20-min bouts with a 10-min rest before
      bout 1 and between bouts. Sweat was collected into plastic bags attached to the
      subject's lower back. During bout 1, sweat from girls and boys had higher Lac-
      concentrations (23.6 +/- 1.2 and 21.2 +/- 1.7 mM; P < 0.05) than sweat from women
      and men (18.2 +/- 1.9 and 14.8 +/- 1.6 mM, respectively), but Lac- was weakly
      associated with SR (P > 0.05; r = -0.27). Sweat Lac- concentration dropped during
      exercise bout 2, reaching similar levels among all groups (overall mean = 13.7 +/
      0.4 mM). Children had a higher sweat NH3 than adults during bout 1 (girls = 4.2
      +/- 0.4, boys = 4.6 +/- 0.6, women = 2.7 +/- 0.2, and men = 3.0 +/- 0.2 mM; P <
      0.05). This difference persisted through bout 2 only in females. On average,
      children's sweat pH was lower than that of adults (mean +/- SEM, girls = 5.4 +/-
      0.2, boys = 5.0 +/- 0.1, women = 6.2 +/- 0.5, and men = 6.2 +/- 0.4 for bout 1,
      and girls = 5.4 +/- 0.2, boys = 6.5 +/- 0.5, women = 5.2 +/- 0.2, and men = 6.9
      +/- 0.4 for bout 2). This may have favored NH3 transport from plasma to sweat as
      accounted for by a significant correlation between sweat NH3 and H+ (r = 0.56).
      Blood pH increased from rest (mean +/- SEM; 7.3 +/- 0.02) to the end of exercise
      (7.4 +/- 0.01) without differences among groups. These results, however, are
      representative of sweat induced by moderate exercise in the absence of acidosis.

PMID- 17225007
TI  - In vivo estimation of stratum corneum thickness from water concentration profiles
      obtained with Raman spectroscopy.
AB  - Stratum corneum thickness was estimated from water concentration profiles of the
      skin measured by a confocal Raman spectrometer. Stratum corneum apparent
      thickness (SCAT) was defined as the depth where the water content reached an
      almost constant value. Site variations were determined using 15 healthy Japanese
      subjects (6 males, 9 females), and age variations at the cheek and forearm were
      examined using 27 female Japanese subjects. There were marked site variations in
      mean SCAT; 16.8 microm for cheek, 22.6 microm for volar forearm, 29.3 microm for
      back of the hand, and 173.0 microm for palm. These variations were similar to
      reported stratum corneum thickness values obtained in biopsy tissues. The SCAT
      tended to become age-dependently thicker at the forearm, but not at the cheek. In
      addition, SCAT was increased up to two-fold by hydration for 90 min, while lesser
      increases were seen with shorter hydration periods.

PMID- 17225008
TI  - Histamine, but not leukotriene C4, is an essential mediator in cold urticaria
      wheals.
AB  - In addition to histamine, leukotriene C4 (LTC4) might also play a role in
      mediating cold urticaria wheals. To study the significance of LTC4 vs. histamine,
      6 patients with cold urticaria were challenged with the ice cube test before and
      after ingestion of 10 mg cetirizine (antihistamine), 10 mg montelukast
      (leukotriene antagonist) or a combination of both drugs. Cetirizine diminished
      the cold-induced wheal by 50+/- 42%. Montelukast had no significant effect, and
      the combination of both drugs diminished the wheal by 37+/- 33%. Furthermore, a
      skin microdialysis technique detected the release of histamine in the cold
      induced wheal, whereas no LTC4 release was detected. In conclusion, the
      antihistamine is effective and histamine is released, whereas the leukotriene
      antagonist is not effective and LTC4 is not released in the cold urticaria wheal.

PMID- 17225009
TI  - High Prevalence of Torque teno (TT) virus in classical Kaposi's sarcoma.
AB  - Human herpes virus 8 infection is the primary and necessary factor in the
      development of Kaposi's sarcoma, but is not sufficient per se to trigger the
      onset of the disease. In order to search for virological cofactors associated
      with the occurrence of the disease, we investigated the prevalence of active
      infection by two newly discovered viruses, hepatitis G virus and TT virus, among
      patients with classical Kaposi's sarcoma. Serum of 24 patients with Mediterranean
      Kaposi's sarcoma was investigated using polymerase chain reaction and compared
      with that of 68 healthy subjects. Cutaneous samples from patients with Kaposi's
      sarcoma and healthy subjects were investigated for TT virus DNA. No patient had
      serum markers for hepatitis G virus. TT virus DNA was present in the serum of
      21/24 (87.5%) patients and 32/68 (47%) controls (p=0.002). TT virus DNA was
      present in the lesional skin of 5/18 patients with Kaposi's sarcoma (27.7%), but
      not in the skin of controls. TT virus might play a role as a cofactor in the
      clinical emergence of Kaposi's sarcoma in patients infected with Human herpes
      virus 8, perhaps by immunosuppressive effects or by a common transmission pathway
      for these two viruses.

PMID- 17225010
TI  - Five novel mutations of RNA-specific adenosine deaminase gene with dyschromatosis
      symmetrica hereditaria.
AB  - Dyschromatosis symmetrica hereditaria (OMIM127400) is a rare autosomal dominant
      pigmentary genodermatosis caused by mutations in the RNA-specific adenosine
      deaminase (ADAR) gene. This study investigated 5 families and 3 sporadic patients
      with dyschromatosis symmetrica hereditaria in the Chinese Han population from
      Anhui province, China. By direct sequencing, 5 novel ADAR gene mutations
      (c.982C>T, c.1491insA, c.2568_2571delTAAC, c.2969C>G and c.3040G>T) and 3
      mutations described previously (c.3203-2A>G, c.3247C>T and c.3286C>T) were
      identified, all of which were heterozygous. We reviewed a total of 48 mutations
      in the ADAR gene in patients with dyschromatosis symmetrica hereditaria by
      previous reports and speculated that the mutation hotspots on the ADAR gene might
      be located in exons 9-15. The tRNA-specific and double-stranded RNA adenosine
      deaminase domain is essential for the deaminase activity of the ADAR encoded
      protein.

PMID- 17225011
TI  - Absence of an active metabolite for the triazole antifungal pramiconazole.
AB  - Pramiconazole is an antifungal with high potential for the treatment of
      dermatophyte and yeast infections of the skin. It is currently not known whether
      pramiconazole is active alone as the parent agent or assisted by active
      metabolites. The in vitro metabolism as well as the metabolic stability of
      pramiconazole was investigated in subcellular liver fractions and isolated
      hepatocytes of several species. Results indicate that the metabolism of
      pramiconazole was slow, since the enzyme-mediated disappearance of pramiconazole
      was rather slow. To investigate whether pramiconazole was converted into an
      active metabolite in humans, serum samples from healthy volunteers receiving a
      daily dose of 100 or 200 mg pramiconazole for one week were assayed with an agar
      diffusion bioassay and liquid chromatography-tandem mass spectrometry. It was
      concluded that there was no active metabolite present in serum samples from
      healthy volunteers after oral dosing of pramiconazole.

PMID- 17225012
TI  - Effect of UV irradiation on cutaneous cicatrices: a randomized, controlled trial
      with clinical, skin reflectance, histological, immunohistochemical and
      biochemical evaluations.
AB  - The aim of this study was to examine the effect of ultraviolet (UV) irradiation
      on human cutaneous cicatrices. In this randomized, controlled study, dermal punch
      biopsy wounds served as a wound healing model. Wounds healed by primary or second
      intention and were randomized to postoperative solar UV irradiation or to no UV
      exposure. Evaluations after 5 and 12 weeks included blinded clinical assessments,
      skin reflectance measurements, histology, immunohistochemistry, and biochemical
      analyses of the N-terminal propeptide from procollagen-1, hydroxyproline,
      hydroxylysine, and proline. Twelve weeks postoperatively, UV-irradiated
      cicatrices healing by second intention: (i) were significantly pointed out as the
      most disfiguring; (ii) obtained significantly higher scores of colour,
      infiltration and cicatrix area; and (iii) showed significantly higher increase in
      skin-reflectance measurements of skin-pigmentation vs. non-irradiated cicatrices.
      No histological, immunohistochemical or biochemical differences were found. In
      conclusion, postoperative UV exposure aggravates the clinical appearance of
      cicatrices in humans.

PMID- 17225013
TI  - Predicting factors of interstitial lung disease in dermatomyositis and
      polymyositis.
AB  - The aim of this study was to define the predicting factors and evaluate the
      prognosis of interstitial lung disease in dermatomyositis/polymyositis. For the
      period 1995-2005, we retrospectively reviewed the clinical information and
      laboratory data of 56 patients who were diagnosed as definite and probable
      dermatomyositis and polymyositis. Interstitial lung disease is common (41.9%) in
      these patients. Dyspnoea and cough were the two most common initial
      presentations. Anti-Jo1 antibody was more common in those with interstitial lung
      disease. Univariate and multivariate analyses identified primary idiopathic
      dermatomyositis subtype, cough and dyspnoea at onset to be the three independent
      clinical predicting factors of interstitial lung disease. High serum lactate
      dehydrogenase level (>400 U/l) was inversely associated with development of
      interstitial lung disease (OR 0.088, p=0.031). Serum lactate dehydrogenase level
      and presence of anti-Jo1 antibody can serve as laboratory indicators of lung
      complications. Patients with malignancy and older age at onset (more than 60
      years) had poorer prognosis for dermatomyositis/polymyositis (p=0.047 and
      p=0.035, respectively). Interstitial lung disease did not affect the survival of
      dermatomyositis/polymyositis patients.

PMID- 17225014
TI  - Course of Borrelia burgdorferi DNA shedding in urine after treatment.
AB  - Diagnosis of Lyme borreliosis by urine polymerase chain reaction (PCR) has been
      recognized as having better diagnostic sensitivity in patients with erythema
      migrans than serological methods. We made serial tests with 192 urine specimens
      from 70 patients with erythema migrans and 60 urine specimens from 21 patients
      with acrodermatitis chronica atrophicans to evaluate the course of positive urine
      PCR after antibiotic treatment. Before treatment, urine samples from patients
      with erythema migrans showed a positive PCR in 27/34 samples (79%), and those
      from patients with acrodermatitis chronica atrophicans in 7/11 (63%). The
      specificity of bands was proven by hybridization with GEN-ETI-KTM-DEIA kit in
      40/41 samples. Borrelia DNA in urine decreased gradually within the observation
      period of one year in both patients with erythema migrans and acrodermatitis
      chronica atrophicans, and persisted without clinical symptoms in 4/45 patients
      with erythema migrans (8%) after 12 months. Urine PCR can serve as a diagnostic
      method in early Lyme borreliosis and also in seropositive patients with unclear
      clinical symptoms.

PMID- 17225015
TI  - Factors associated with atypical moles in New Hampshire, USA.
AB  - Only a few studies, conducted in Sweden, assessed factors associated with the
      presence of atypical moles in the general population. We conducted a population
      based, case-control study in New Hampshire, USA, to identify factors associated
      with atypical moles. In our study, atypical moles affected 14% of the study
      population. The adjusted odds ratio (OR) was 0.34 (95% confidence interval (CI) =
      0.14-0.80) for those with the highest adulthood recreational sun exposure,
      relative to the lowest. The OR for any freckles, compared to none, was 2.24 (95%
      CI = 1.18-4.25). We found a linear relationship between the number of benign
      moles and the presence of atypical moles (p for trend = 0.0001). The OR was 7.34
      (95% CI = 3.03-17.80) for > 15 benign moles, relative to 0-4. Our data indicate
      that freckles and benign moles, which may reflect melanocytic inducibility, are
      strongly associated with atypical moles. The inverse association with sun
      exposure should be considered with caution.

PMID- 17225016
TI  - Cutaneous manifestations in patients positive for anti-hepatitis C virus
      antibodies.
AB  - Cutaneous diseases can indicate the presence of hepatitis C virus (HCV)
      infection. The aim of this study was to analyse the frequency of cutaneous
      findings in HCV infection and HCV RNA positive cases in Turkey. Fifty consecutive
      patients positive for anti-HCV antibodies,negative controls, and patients
      positive and negative for HCV RNA were examined for any cutaneous findings that
      could be associated with HCV infection. The risk of infected patients developing
      cutaneous finding was higher than for non-infected individuals. Only pruritus
      showed a statistically significant difference in separate assessment of cutaneous
      symptoms. There were no differences in cutaneous findings in HCV RNA positive and
      negative cases. The risk of developing a dermatological finding, especially
      pruritus, was increased in HCV infection.However, because the number of patients
      in this study was too low to allow statistical evaluation of the prevalence of
      dermatological symptoms and diseases, multicentre studies including large numbers
      of patients are needed.

PMID- 17225017
TI  - Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic
      dermatitis in children.
AB  - Tacrolimus ointment is a topical calcineurin inhibitor for the treatment of
      atopic dermatitis. The primary objective of this open-label study was to assess
      the long-term safety of tacrolimus ointment. The primary end-point was the
      incidence of adverse events. Secondary end-points included the Eczema Area and
      Severity Index and a modified version of this index. A total of 466 children with
      atopic dermatitis, aged 2-15 years, applied 0.03% or 0.1% tacrolimus ointment
      twice daily for up to 29.5 months. Skin burning and pruritus were the most common
      application site events; their prevalence decreased over time. There was no
      increase in viral infections or other adverse events over time. Laboratory
      profiles were consistent with those reported in atopic populations. Substantial
      improvement in all efficacy end-points was observed by week 2 and maintained
      throughout the study. Long-term treatment with tacrolimus ointment is safe and
      effective in these patients with atopic dermatitis.

PMID- 17225018
TI  - An efficient new formulation of fusidic acid and betamethasone 17-valerate
      (fucicort lipid cream) for treatment of clinically infected atopic dermatitis.
AB  - To relieve the dryness of atopic dermatitis skin, a lipid formulation of fusidic
      acid and betamethasone 17-valerate (Fucicort Lipid cream) was developed as an
      additional treatment option to the established Fucicort cream. The two
      formulations were compared in patients with clinically infected atopic
      dermatitis. A total of 629 patients were randomized to twice daily double-blind
      treatment for 2 weeks with either Fucicort Lipid cream, Fucicort cream, or the
      new lipid cream vehicle. Clinical assessment was based on a Total Severity Score
      of the eczematous lesions. Bacteriological samples were taken at inclusion and at
      subsequent visit(s) if clinically infected lesions persisted. At the end of
      treatment, the mean reduction in Total Severity score was 82.9% in the lipid
      cream group, 82.7% in the cream group, and 33.0% in the vehicle group. The
      percentage of patients with a successful bacteriological response was 89.7%,
      89.6% and 25.0%, respectively. Thus, the clinical and anti-bacterial effect of
      the lipid cream was found to be similar to that of the established cream
      formulation, and significantly better than that of the vehicle. The new lipid
      formulation, therefore, offers an efficient, safe and well-tolerated alternative
      for the short-term treatment of clinically infected atopic dermatitis.

PMID- 17225019
TI  - Vulvar lichen sclerosus: 11 women treated with tacrolimus 0.1% ointment.
AB  - Lichen sclerosus is a chronic relapsing disease, usually treated with ultra
      potent corticosteroids. As immunological alterations are considered important
      aetiopathogenetic factors in lichen sclerosus, the new immunomodulating topical
      agents, such as tacrolimus and pimecrolimus, have been employed sporadically as
      alternative therapies. The aim of this study was to evaluate the therapeutic
      effects of tacrolimus 0.1% ointment in lichen sclerosus in 11 patients
      unresponsive or poorly responsive to previous treatments. Tacrolimus 0.1%
      ointment was applied twice daily for 6 weeks, then tapered over a further 6
      weeks. Symptoms and objective parameters were evaluated and quantified at the
      start, after 6 weeks, at the end of the topical treatment, and at follow-up
      visits. Improvement or remission of symptoms was observed in the patients who
      completed the study, while objective parameters were poorly influenced and often
      were not related to symptom behaviour. Topical tacrolimus can be considered an
      alternative treatment for lichen sclerosus.

PMID- 17225021
TI  - Idiopathic CD4+ T-cell lymphocytopaenia associated with recalcitrant viral warts
      and squamous malignancy.

PMID- 17225020
TI  - Treatment of ocular cicatricial pemphigoid with the tumour necrosis factor alpha
      antagonist etanercept.

PMID- 17225022
TI  - Psoriasiform drug eruptions under anti-TNF treatment of arthritis are not true
      psoriasis.

PMID- 17225023
TI  - Quadruple extra-mammary Paget's disease.

PMID- 17225024
TI  - Ichthyosiform mycosis fungoides: a neoplastic acquired ichthyosis.

PMID- 17225025
TI  - Epidermal naevus with eccrine duct changes: an orthokeratotic variant of eccrine
      ostial and dermal duct naevus?

PMID- 17225026
TI  - Treatment of scalp psoriasis with betamethasone dipropionate and calcipotriol two
      compound product.

PMID- 17225027
TI  - Lichen aureus induced by interferon-alpha plus ribavirin.

PMID- 17225028
TI  - Papular and reticular elastolytic giant cell granuloma: rapid spontaneous
      regression.

PMID- 17225029
TI  - Long-lasting scrofuloderma of hands and foot.

PMID- 17225030
TI  - Alopecia neoplastica due to metastatic colon adenocarcinoma.

PMID- 17225031
TI  - Motor imagery and stroke rehabilitation: a critical discussion.
AB  - Motor disorders are a frequent consequence of stroke and much effort is invested
      in the re-acquisition of motor control. Although patients often regain some of
      their lost function after therapy, most remain chronically disabled. Functional
      recovery is achieved largely through reorganization processes in the damaged
      brain. Neural reorganization depends on the information provided by sensorimotor
      efferent-afferent feedback loops. It has, however, been shown that the motor
      system can also be activated "offline" by imagining (motor imagery) or observing
      movements. The discovery of mirror neurones, which fire not only when an action
      is executed, but also when one observes another person performing the same
      action, also show that our action system can be used "online" as well as offline.
      It is an intriguing question as to whether the information provided by motor
      imagery or motor observation can lead to functional recovery and plastic changes
      in patients after stroke. This article reviews the evidence for motor imagery or
      observation as novel methods in stroke rehabilitation.

PMID- 17225032
TI  - Muscle strength and muscle training after stroke.
AB  - For many individuals who have experienced a stroke, muscle weakness is the most
      prominent impairment. Both the theoretical and statistical relationships between
      muscle weakness and performance at functional activities suggest that weakness
      may be an appropriate target for therapeutic interventions. Researchers
      investigating the outcomes of strengthening regimens after stroke have routinely
      shown that resistance exercise leads to increased muscle strength, but that
      strength is typically measured using the same maneuvers that were used in
      training. Evidence supporting the use of strengthening regimens to reduce
      limitations in functional activity is equivocal.

PMID- 17225033
TI  - Inpatient stroke rehabilitation: a comparative study of admission criteria to
      stroke rehabilitation units in four European centres.
AB  - OBJECTIVE: To explore the clinical and non-clinical factors involved in decision
      making concerning admission to European stroke rehabilitation units. DESIGN:
      Observational study on case-mix at intake combined with questionnaires and semi
      structured interviews with the medical consultants of each European stroke
      rehabilitation unit. PATIENTS AND SETTINGS: Clinical data on 532 first-ever
      patients after stroke. Medical consultants from 6 European stroke rehabilitation
      units in 4 European countries (UK, Belgium, Germany and Switzerland). METHODS:
      Standardized clinical assessments within 2 days after admission. Questionnaires
      to each medical consultants followed by a qualitative round of semi-structured
      interviews. RESULTS: Case-mix of patients after stroke was significantly
      different between European stroke rehabilitation units. Clinical criteria for
      admission were seldom explicit and were evaluated differently between the
      European stroke rehabilitation units. In the UK units, diagnosis of stroke was
      the only criterion for admission. In the Belgian, German and Swiss units, pre
      morbid conditions were taken into account in admission decisions. The likelihood
      of discharge home was considered highly important in the Swiss units. CONCLUSION:
      Case-mix differences at intake could be linked to different appraisals of
      clinical and non-clinical factors of patients after stroke. The findings urge us
      to be more explicit about decision-making processes at admission in order to
      provide a more comprehensive insight into the interplay between context and
      process of care.

PMID- 17225034
TI  - Can rehabilitation in the home setting reduce the burden of care for the next-of
      kin of stroke victims?
AB  - BACKGROUND: More evidence of the efficacy of caregiver interventions is needed.
      The aim of this study was to evaluate whether counselling in the home setting
      reduces the caregiver burden. METHODS: Thirty-six patients after stroke, median
      age 53 years, with a close family member, were selected for an evaluation of the
      burden of care and 35 participated. They were part of a randomized controlled
      trial, comparing rehabilitation in the home setting with outpatient
      rehabilitation. In the home setting, counselling about the stroke and its
      consequences was included. Assessments with the Caregiver Burden scale were made
      at 3 weeks, 3 months and one year after discharge. RESULTS: The burden of the 2
      groups did not differ. After the intervention, there was a tendency to a lower
      burden for the home setting. The burden for the home setting was then unchanged
      from 3 weeks to 1 year, while outpatient rehabilitation showed a reduced burden
      over time. For the home setting, significant correlations to activity level were
      seen after the intervention. CONCLUSION: A positive effect of counselling was
      seen, as the home setting burden tends to be lower after the intervention, while
      outpatient rehabilitation seems to adjust with time. The results suggest that
      counselling reduces burden and the remaining burden is associated with the
      patient's ability.

PMID- 17225035
TI  - Are clinical characteristics associated with upper-extremity hypertonia in severe
      ischaemic supratentorial stroke?
AB  - OBJECTIVE: The primary goal of this study was to identify clinical risk factors,
      in addition to muscle weakness, for upper-extremity hypertonia in patients with
      severe ischaemic supratentorial stroke. The secondary goal was to investigate the
      time course of upper-extremity hypertonia in these patients during the first 26
      weeks post-stroke. DESIGN: Inception cohort. PATIENTS: Forty-three consecutive
      patients with an acute ischaemic supratentorial stroke and an initial upper
      extremity paralysis admitted to an academic hospital. MAIN OUTCOME MEASURES: 
      PRIMARY OUTCOME: hypertonia assessed by the Ashworth scale at week 26 post
      stroke. Potential risks factors: motor functions assessed by the upper-extremity
      subscore of the Fugl-Meyer motor assessment, Barthel Index at week 1,
      consciousness, sensory disturbances, apraxia, neglect, and hyper-reflexia.
      Secondary outcome: time course of upper-extremity hypertonia by assessing its
      prevalence at 6 consecutive moments post-stroke during a follow-up period of 26
      weeks. RESULTS: Twenty-five patients (63%) developed hypertonia during the follow
      up period of 26 weeks. During this period, the prevalence of hypertonia followed
      a rather dynamic course, with cases of early, transient and late hypertonia.
      Univariate analyses yielded none of the selected clinical characteristics as
      significantly associated with hypertonia. CONCLUSION: Despite the high incidence
      of hypertonia (63%) observed, none of the selected clinical characteristics could
      be identified as a risk factor for hypertonia.

PMID- 17225036
TI  - Are neuroradiological or neurophysiological characteristics associated with upper
      extremity hypertonia in severe ischaemia in supratentorial stroke?
AB  - OBJECTIVE: The primary goal was to identify the neuroradiological and
      neurophysiological risk factors for upper-extremity hypertonia in patients with
      severe ischaemic supratentorial stroke. DESIGN: Inception cohort. PATIENTS: Forty
      three consecutive patients with an acute ischaemic supratentorial stroke and an
      initial upper-extremity paralysis admitted to an academic hospital recruited over
      a 1.5-year period. MAIN OUTCOME MEASURES: Upper-extremity hypertonia was assessed
      by the Ashworth scale and clinically relevant hypertonia was defined as Ashworth
      scale >or=2. Any association of (clinically relevant) hypertonia with
      neuroradiological (lesion side, extent of lesion, and stroke history), and
      neurophysiological (motor-evoked potential and silent period) characteristics was
      investigated. RESULTS: Associations between hypertonia and the selected
      neuroradiological and neurophysiological risk factors were generally low.
      Univariate analyses yielded none of the selected neuroradiological or
      neurophysiological characteristics as significantly associated with hypertonia.
      CONCLUSION: Despite the high incidence of hypertonia in these patients, we could
      not identify any of the selected neuroradiological or neurophysiological
      characteristics as a risk factor for hypertonia.

PMID- 17225037
TI  - Little therapy, little physical activity: rehabilitation within the first 14 days
      of organized stroke unit care.
AB  - OBJECTIVE: To examine rehabilitation interventions and resulting physical
      activity patterns of patients managed in acute stroke units to help inform
      development of a randomized controlled trial of very early rehabilitation.
      DESIGN: An open observational study of patient activity and therapist report of
      patient interventions. A survey of stroke unit resources. METHODS: Patients less
      than 14 days post-stroke from 5 metropolitan stroke units were observed over 2
      consecutive weekdays at 10-minute intervals between 08.00 h and 17.00 h. Physical
      activity, location and person(s) present were ascertained at each observation.
      Therapists completed treatment records. Senior staff completed stroke unit
      surveys. RESULTS: Patients after stroke (n=58) were with therapists 5.2% of the
      observed day. Few patients (17.1%) received daily therapy by more than one
      therapist. When patients received therapy, average session times were 24 minutes
      of physiotherapy, 23 minutes of occupational therapy and 33 minutes of speech
      pathology. The more time that family members were present, the longer the
      treatment time. Four to 11 min of upper-limb therapy was provided. Muscle
      weakness and left hemiparesis were associated with less upper-limb activity.
      CONCLUSION: These acute stroke care units were resourced according to recommended
      staff-patient ratios. Patients received little therapy and had low levels of
      physical activity.

PMID- 17225038
TI  - Return to work and health-related quality of life after burn injury.
AB  - OBJECTIVE: Although severe burn injury is associated with long-term
      rehabilitation and disability, research on returning to work in burn patients is
      limited. The aims of this study were: (i) to explore injury- and personality
      related predictors of returning to work, and (ii) to compare health-related
      quality of life and health outcome in working versus non-working individuals.
      DESIGN: Cross-sectional study. SUBJECTS: Forty-eight former patients with pre
      burn employment were evaluated on average 3.8 years after the burn. METHODS: Data
      were collected from medical records and by a questionnaire in which the patients
      were asked about their main activity status described in the terms: work,
      studies, pension, disability pension, sick leave or unemployment. It also
      contained the Swedish universities Scales of Personality, SF-36, Burn Specific
      Health Scale-Brief, items assessing fear-avoidance, Impact of Event Scale-Revised
      and Hospital Anxiety and Depression Scale. RESULTS: Thirty-one percent had not
      returned to work. In logistic regression, returning to work was associated with
      time since injury, the extent of full-thickness injuries, and the personality
      trait embitterment. Those who did not work had lower health-related quality of
      life, poorer burn-specific health, more fear-avoidance and more symptoms of
      posttraumatic stress disorder, but they did not differ from those who were
      working regarding general mood. CONCLUSION: Returning to work was explained by
      both injury severity and personality characteristics. Those who did not work were
      characterized by low health-related quality of life and poorer trauma-related
      physical and psychological health.

PMID- 17225040
TI  - Use of International Classification of Functioning, Disability and Health (ICF)
      to describe patient-reported disability in multiple sclerosis and identification
      of relevant environmental factors.
AB  - OBJECTIVE: To use the International Classification of Functioning, Disability and
      Health (ICF) to describe patient-reported disability in multiple sclerosis and
      identify relevant environmental factors. METHODS: Cross-sectional survey of 101
      participants in the community. Their multiple sclerosis-related problems were
      linked with ICF categories (second level) using a checklist, consensus between
      health professionals and the "linking rules". The impact of multiple sclerosis on
      health areas corresponding to 48 ICF categories was also assessed. RESULTS: A
      total of 170 ICF categories were identified (mean age 49 years, 72 were female).
      Average number of problems reported was 18. The categories include 48 (42%) for
      body function, 16 (34%) body structure, 68 (58%) activities and participation and
      38 (51%) for environmental factors. Extreme impact in health areas corresponding
      to ICF categories for activities and participation were reported for mobility,
      work, everyday home activities, community and social activities. While those for
      the environmental factors (barriers) included products for mobility, attitudes of
      extended family, restriction accessing social security and health resources.
      CONCLUSION: This study is a first step in the use of the ICF in persons with
      multiple sclerosis and towards development of the ICF Core set for multiple
      sclerosis from a broader international perspective.

PMID- 17225039
TI  - Impact of age and co-morbidity on the functioning of patients with sequelae of
      poliomyelitis: a cross-sectional study.
AB  - OBJECTIVE: To investigate the impact of age and co-morbidity on the functional
      independence and perceived physical functioning of patients with sequelae of
      poliomyelitis. DESIGN: Cross sectional study. SUBJECTS: A convenience sample of
      168 patients with sequelae of poliomyelitis, aged 45-85 years, recruited from 2
      university hospitals. METHODS: Outcome measures were Functional Independence
      Measure (FIMTM) for functional independence, Short Form-36 (SF-36) for physical
      functioning and general mental health, Cumulative Illness Rating Scale (CIRS) for
      co-morbidity. RESULTS: FIMTM scores were significantly lower for the 65-85 year
      age group than for the 45-54 year age group. No differences in the SF-36 were
      found between the age groups, except that the SF-36 general mental health sub
      scale score was significantly better in the 65-85 year age group than in the 45
      54 year age group. The CIRS score increased significantly with age. Linear
      regression showed that age, gender, polio severity, and 4 co-morbidity scores
      ("cardiac", "vascular", "endocrine, metabolic"and "muscle, bone, skin") were
      significantly and inversely associated with functional independence and physical
      functioning. CONCLUSION: The level of functional independence of elderly former
      poliomyelitis patients is lower than that of younger patients. Specific attention
      should be paid to co-morbidity and ageing in this increasingly older population
      of polio survivors, since they negatively affect functional independence and
      perceived functioning.

PMID- 17225041
TI  - Assessing observer agreement when describing and classifying functioning with the
      International Classification of Functioning, Disability and Health.
AB  - OBJECTIVE: The International Classification of Functioning, Disability and Health
      (ICF) is used increasingly to describe and classify functioning in medicine
      without being a psychometrically sound measure. All categories of the ICF are
      quantified using the same generic 0-4 scale. The objective of this study was to
      assess observer agreement when describing and classifying functioning with the
      ICF. DESIGN: A second-level category of the ICF, d430 lifting and carrying
      objects, was used as an example. To the qualifiers of this category, clinically
      meaningful definitions were assigned. Data were collected in a cross-sectional
      survey with repeated measurement. We report raw, specific and chance-corrected
      measures or agreement, a graphical method and the results of log-linear models
      for ordinal agreement. SUBJECTS/PATIENTS: A convenience sample of patients
      requiring physical therapy in an acute hospital. RESULTS: Twenty-five patients
      were assessed twice by 2 observers. Raw agreement was 0.52. Kappa was 0.36,
      indicating fair agreement. Different hierarchical log-linear models indicated
      that the strength of agreement was not homogeneous over all categories.
      CONCLUSION: Observer agreement has to be evaluated when describing and
      classifying functioning using the ICF Qualifiers'scale. When assessing inter
      observer reliability, the first step is to calculate a summary statistic.
      Modelling agreement yields valuable insight into the structure of a contingency
      table, which can lead to further improvement of the scale.

PMID- 17225042
TI  - Efficacy of a flexible orthotic device in patients with osteoporosis on pain and
      activity of daily living.
AB  - OBJECTIVE: To study the efficacy of a flexible orthotic device in patients with
      osteoporosis. DESIGN: Open observational study. PATIENTS: Fifty patients with
      osteoporosis. METHODS: An open observational study was performed on 50 patients
      with osteoporosis in order to investigate the efficacy of a new osteoporosis
      orthotic device, which is an elastic back support with paravertebral air chamber
      pads. The outcome parameters were pain, activities of daily living, individual
      compliance and comfort. The observation period was approximately 2.5 months, and
      the orthotic device was worn continuously during daytime. RESULTS: There was a
      highly significant reduction in pain under exertion from mean 6.1 (SD 1.7) to 4.5
      (SD 1.4) (p < 0.00001), pain when driving (from 5.2 (SD 2.4) to 3.8 (SD 1.9) (p <
      0.00001)), and pain at rest from 4.1 (SD 2.4) to 3.1 (SD 1.9) (p < 0.0001). About
      50% of the patients judged their ability to perform everyday activities as "much
      better"or "better". If physiotherapy was interrupted upon onset of orthosis
      treatment, the results were significantly worse than in patients with continued
      physiotherapy. CONCLUSION: This orthotic device could be a useful addition to the
      medical care of patients with osteoporosis and a complement to drug treatment and
      physiotherapy with regular exercises, which should be continued.

PMID- 17225043
TI  - Motivating disability pensioners with back pain to return to work--a randomized
      controlled trial.
AB  - OBJECTIVE: To investigate the outcome of a brief vocational-oriented intervention
      aiming to motivate disability pensioners with back pain to return to work, and to
      evaluate prognostic factors for having entered a return to work process during
      the following year. DESIGN: A randomized controlled trial was conducted.
      SUBJECTS: Participants (n = 89) (mean age 49 years, 65% women) who had received
      disability pension for more than one year were randomized into an intervention
      group (education, reassurance, motivation, vocational counselling, n = 45) and a
      control group (n = 44). METHODS: Primary outcome measures were return to work or
      having entered a return to work process. Secondary outcome measures were life
      satisfaction, disability, fear avoidance behaviour and expectancy. RESULTS: The
      intervention had no statistically significant effect on return to work or having
      entered a return to work process at 1-year follow-up. Twice as many in the
      intervention group (n = 10, 22%) had entered a return to work process compared
      with the controls (n = 5, 11%). The number needed to treat was 9.2 (95%
      confidence interval (CI) = 3.4, Inf). Only minor differences in secondary outcome
      measures were demonstrated. Positive expectancy, better physical performance and
      less pain were related to return to work. CONCLUSION: The effort of returning
      disability pensioners to work by a brief vocational-oriented intervention may be
      of clinical relevance. The effect needs to be explored further in larger samples
      of disability pensioners.

PMID- 17225045
TI  - Apparatus for dynamic balance training during treadmill walking.
AB  - OBJECTIVE: A presentation of a novel apparatus for dynamic balance training
      during treadmill walking, which was tested in a case study. SUBJECT: The subject
      was a man with incomplete chronic spinal cord injury (C5), graded D on the
      American Spinal Injury Association Impairment Scale. METHODS: Following a 6-month
      baseline period, 4 weeks of control treatment (treadmill walking) and a
      subsequent 4 weeks of experimental treatment (treadmill walking assisted by the
      apparatus) were compared. Outcome measures were Lower Extremities Motor Score,
      Berg Balance Scale, 10-metre walking test and 9-minute walking test. RESULTS:
      During the baseline period the changes in the outcome measures were small. After
      the control treatment the balance score remained unchanged, while walking speed
      and walking endurance increased moderately. Experimental treatment resulted in
      further substantial changes in balance and walking endurance scores, while
      further increase in walking speed was moderate. At follow-up these values were
      maintained. Lower Extremities Motor Scores were almost identical in all study
      phases. CONCLUSION: The subject's walking and balancing abilities improved
      moderately after the control treatment, while greater improvement occurred during
      experimental treatment. This indicates that the apparatus developed might be an
      important tool for facilitating dynamic balancing training during treadmill
      walking.

PMID- 17225044
TI  - Effects of exercise intervention on patients with stroke with prior coronary
      artery disease: aerobic capacity, functional ability, and lipid profile: a pilot
      study.
AB  - OBJECTIVE: To assess the effects of exercise intervention on aerobic capacity,
      functional ability and lipid profile in patients after stroke with prior coronary
      artery disease. PATIENTS: Fifteen patients after stroke with prior coronary
      artery disease. METHODS: Patients were enrolled in a moderate-intensity exercise
      intervention using a graded treadmill for 12 weeks. Before and after the
      intervention, their aerobic capacity and functional ability were assessed by the
      exercise testing and Barthel index, respectively. The total cholesterol (TC),
      lowdensity lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol
      (HDL), triglyceride, and TC/HDL were also evaluated using an enzyme auto
      analyser. RESULTS: After training, the patients'absolute peak oxygen consumption
      (VO2) was increased (p < 0.01); their functional ability was significantly
      improved (p < 0.01); and their TC, LDL, triglyceride, and TC/HDL levels were
      significantly reduced (p < 0.01). However, HDL level did not change
      significantly. In addition, Pearson analysis demonstrated a strong correlation
      between the increase in peak VO2 and the decrease in TC/HDL (r = -0.72, p <
      0.01). CONCLUSION: These results suggest that exercise intervention is beneficial
      for aerobic capacity, functional ability, and some parts of the lipid profile in
      patients after stroke with prior coronary artery disease.

PMID- 17225046
TI  - Ductal carcinoma in situ: correlations between high-resolution magnetic resonance
      imaging and histopathology.
AB  - PURPOSE: The aim of this retrospective study was to determine and correlate
      contrast-enhanced areas and multiple internal dark dots and lines on high
      resolution magnetic resonance imaging (HR-MRI) with findings in surgical
      specimens of ductal carcinoma in situ (DCIS) and to evaluate the ability of HR
      MRI to detect DCIS lesions and clarify HR-MRI features characteristic of DCIS.
      MATERIALS AND METHODS: This study retrospectively reviewed 11 patients diagnosed
      with DCIS who had undergone HR-MRI. Pathological findings and results of HR-MRI
      were compared, and causes of periductal enhancements were analyzed. RESULTS: In
      all patients, HR-MRI using microscopic coils revealed ductally, segmentally, or
      regionally enhanced areas containing multiple dark dots and lines, representing
      local enhancement of stroma adjacent to the mammary duct containing DCIS.
      Neovascularization, infiltration of inflammatory cells, and focal edema occurred
      in enhanced periductal stroma. Poorly enhanced linear or dot-like structures
      correlated with dilated mammary ducts displaying necrosis and tumor impaction.
      CONCLUSION: DCIS was successfully depicted on HR-MRI using a microscopy coil in
      all 11 cases. Ductal, segmental, or regional areas of enhancement with multiple
      dark dots and lines on HR-MRI corresponded to mammary glands containing DCIS with
      periductal enhancement.

PMID- 17225047
TI  - Comparison of 4 MV photon surface dose among Varian, Siemens, and Elekta linear
      accelerators for tangential breast treatment: a phantom study.
AB  - PURPOSE: We have compared the differences in a 4-MV photon surface dose among
      Varian, Siemens, and Elekta linear accelerators (linacs) with wedges for
      tangential breast treatment. MATERIALS AND METHODS: The wedge factor and the
      surface dose were measured using a solid water phantom and an ion chamber for
      each linear accelerator with various field sizes and wedge angles. A tangential
      treatment plan was applied to an elliptical hollow cylinder water phantom with a
      radiochromic film placed thereon. A dose was delivered to a simulated target in
      the phantom, and the resulting dose distribution was analyzed using a film
      scanner. RESULTS: Varian's wedges resulted in the highest wedge factors, ranging
      from 0.37 to 0.75 depending on the wedge angles. Varian's wedges led to the
      highest normalized skin doses, ranging between 0.40 and 0.73 depending on the
      wedge angles and field sizes. In the cylinder phantom test with two tangential
      beams, the Varian linac provided a nearly 20% higher maximum dose than the
      Siemens and Elekta linacs. CONCLUSION: The Varian linac resulted in the highest
      surface doses, and the Elekta linac led to the lowest for nearly all the
      measurement conditions we employed, including open beams.

PMID- 17225048
TI  - Prediction of aortic peak enhancement in monophasic contrast injection protocols
      at multidetector CT: phantom and patient studies.
AB  - PURPOSE: The aim of this study was to investigate whether it is possible to
      predict aortic peak enhancement (APE) from the contrast dose and injection rate.
      MATERIALS AND METHODS: We first undertook an experimental study using a flow
      phantom that simulates the human circulation. We delivered 90-150 ml of iomeprol
      350 at various injection rates and measured the APE values of the simulated
      aorta. In our clinical study we randomized 20 patients into four groups. In
      groups A, B, and C the iodine dose per kilogram of body weight (BW) ranged from
      450 to 600 mg, and the injection duration was fixed at 30 s; group D received 450
      mg/kg over 25 s. We then measured APE in all patients at the whole aorta,
      averaged the three highest values, and took the result as APE. RESULTS: In the
      phantom study, the decision coefficient for the best-fit equation obtained by
      multiple regression analysis of the relation between the iodine dose and
      injection rate and the simulated APE was high (0.93). In the patient study, the
      predicted APE values almost corresponded with the averaged APE values when we
      applied the fitness equation. CONCLUSION: Using our fitness equation, APE on
      contrast-enhanced computed tomography can be predicted from the iodine dose and
      the contrast injection rate per patient weight.

PMID- 17225049
TI  - CT-based postimplant dosimetry of prostate brachytherapy: comparison of 1-mm and
      5-mm section CT.
AB  - PURPOSE: The aim of this study was to compare the outcomes between 1-mm and 5-mm
      section computed tomography (CT)-based postimplant dosimetry. MATERIALS AND
      METHODS: A series of 21 consecutive patients underwent permanent prostate
      brachytherapy. The postimplant prostate volume was calculated using 1-mm and 5-mm
      section CT. One radiation oncologist contoured the prostate on CT images to
      obtain the reconstructed prostate volume (pVol), prostate V(100) (percent of the
      prostate volume receiving at least the full prescribed dose), and prostate D(90)
      (mean dose delivered to 90% of the prostate gland). The same radiation oncologist
      performed the contouring three times to evaluate intraobserver variation and
      subjectively scored the quality of the CT images. RESULTS: The mean +/-1 SD
      postimplant pVol was 20.17 +/- 6.66 cc by 1-mm section CT and 22.24 +/- 8.48 cc
      by 5-mm section CT; the difference in the mean values was 2.06 cc (P < 0.01). The
      mean postimplant prostate V(100) was 80.44% +/- 7.06% by 1-mm section CT and
      77.33% +/- 10.22% by 5-mm section CT. The mean postimplant prostate D(90) was
      83.28% +/- 10.81% by 1-mm section CT and 78.60% +/- 15.75% by 5-mm section CT. In
      the evaluation of image quality, 5-mm section CT was assigned significantly
      higher scores than 1-mm section CT. In regard to intraobserver variation, 5-mm
      section CT revealed less intraobserver variation than 1-mm section CT.
      CONCLUSION: Our current results suggested that the outcomes of postimplant
      dosimetry using 1-mm section CT did not improved the results over those obtained
      using 5-mm section CT in terms of the quality of the CT image or reproducibility.

PMID- 17225050
TI  - Erythema multiforme and Stevens-Johnson syndrome following radiotherapy.
AB  - Erythema multiforme (EM) and Stevens-Johnson syndrome (SJS) are thought to be
      hypersensitivity syndromes with various causes, and radiotherapy might be one of
      the causes of these syndromes. We herein report two cases of EM/SJS following
      radiotherapy. The first case was a 63-year-old woman with breast cancer. At the
      end of postoperative radiotherapy with 60 Gy, severe pruritic erythema appeared
      in the irradiated area and spread over the whole body. She was diagnosed with EM
      by a skin biopsy. The second case was a 77-year-old woman with uterine cervical
      cancer who underwent postoperative radiotherapy. At a dose of 30.6 Gy, pruritic
      redness appeared in the irradiated area and the precordial region, and it became
      widespread rapidly with polymorphic transformation. Although without any
      histological confirmation, SJS was strongly suspected because of her pruritic
      conjunctivitis. Because both patients were given medicines during irradiation,
      radiotherapy may not be the only cause of EM/SJS. However, it should be noted
      that radiotherapy might trigger EM/SJS.

PMID- 17225051
TI  - Novel correction methods as alternatives for the six-dimensional correction in
      CyberKnife treatment.
AB  - PURPOSE: During CyberKnife treatment, the 6D correction method is used to correct
      patient positional errors, including rotational ones. We developed novel
      correction methods for translating rotational errors into 3D, with the aim of
      making their correction safer than with 6D correction and as accurate as
      possible. MATERIALS AND METHODS: These novel correction methods were named the
      gravity correction and the beam correction method. With the gravity correction
      method, the beam coordinates after rotation are corrected to match the tumor
      gravity point with 3D translational components translated by the affine
      transformation matrix. For beam correction, the beam coordinates are corrected to
      match the translated tumor target coordinates for each treatment beam. The
      effectiveness and impact of these methods were demonstrated by means of dose
      volume histogram (DVH) shift evaluation. For analysis of the treatment data of 10
      patients, the treatment beam was rotated in three patterns of rotational degree
      and corrected with the two methods. The amount of tumor gravity point shift in
      the rotation was also calculated, and the deterioration of the tumor DVH was
      studied. RESULTS: In the case of +/-1 degrees , +/-3 degrees , and +/-1 degrees
      rotation for the X, Y, Z axes, the tumor gravity point of all 10 patients moved
      around 2.4 mm on average. Tumor DVH was deteriorated worse as the distance
      between the tumor gravity point and the rotational origin became more distant.
      With the planned D90, which represents the dose above which 90% of the tumor
      volume is irradiated set at 100%, the postrotational average D90 dose
      deteriorated to 96.12% after (+/-1 degrees , +/-3 degrees , and +/-1 degrees )
      rotation. The dose was improved to 99.9% (SD +/- 0.41) after the gravity
      correction, or to 99.87% (SD +/- 0.55) after the beam correction. CONCLUSION: The
      correction methods developed by us can correct tumor DVH findings to the same
      degree as with 6D correction and are safer because the movement required for
      correcting the linac is not rotational but translational only.

PMID- 17225052
TI  - Cardiac imaging using 256-detector row four-dimensional CT: preliminary clinical
      report.
AB  - PURPOSE: Along with the increase of detector rows on the z-axis and a faster
      gantry rotation speed, the spatial and temporal resolutions of the multislice
      computed tomography (CT) have been improved for noninvasive coronary artery
      imaging. We investigated the feasibility of the second specification prototype
      256-detector row four-dimensional CT for assessing coronary artery and cardiac
      function. MATERIALS AND METHODS: The subjects were five patients with coronary
      artery disease. Contrast medium (40-60 ml) was intravenously administered at the
      rate of 3-4 ml/s. The patient's whole heart was scanned for 1.5 s to cover at
      least one cardiac cycle during breathholding without electrocardiographic gating.
      Parameters used were 0.5 mm slice thickness, 0.5 s/rotation, 120 Kv, and 350 mA,
      with a half-scan reconstruction algorithm (temporal resolution 250 ms). Twenty
      six transaxial datasets were reconstructed at intervals of 50 ms. RESULTS: The
      assessability of the coronary arteries in AHA segments 1, 2, 3, 5, 6, 7, 9, and
      11 was visually evaluated, resulting in 29 of 32 (90.9%) segments being
      assessable. Functional assessment was also performed using animated movies
      without banding artifacts in all cases. CONCLUSIONS: The 256-detector row four
      dimensional CT can assess the coronary artery and cardiac function using data
      during 1.5 s without banding artifacts.

PMID- 17225053
TI  - The association between hyperuricemia and the Trp64Arg polymorphism of the beta-3
      adrenergic receptor.
AB  - The object of this study was to determine the association of Trp64Arg
      polymorphism with hyperuricemia. This study is an age-matched, case-controlled
      study of 203 hyperuricemic and 203 normouricemic men. The frequency of genotypes
      was compared between the two groups. Possible confounding metabolic variables
      were included in a multiple logistic regression model for multivariate
      adjustment. The genotype frequencies of Trp64Trp, Trp64Arg, and Arg64Arg in
      hyperuricemic and normouricemic groups are respectively 130, 69, and 4 (64.0%,
      34.0%, 2.0%) and 154, 45, and 4 (75.9%, 22.2%, 2.0%) (P = 0.029, Chi-square
      test). Simple logistic regression analysis indicated that the Trp64Arg genotype
      is significantly associated with hyperuricemia (OR = 1.816, 95% CI (1.167-2.827),
      P = 0.008). Multivariate analysis for controlling metabolic effects also showed a
      significant association with the occurrence of hyperuricemia (OR = 1.937, 95% CI
      (1.149-3.266), P = 0.013). Trp64Arg polymorphism of the beta-3 adrenergic
      receptor may be independently associated with hyperuricemia in males.

PMID- 17225054
TI  - The effect of outfitting style on bone mineral density.
AB  - AIM: Vitamin D deficiency is one of the most important risk factors in the
      development of osteoporosis. Recently, vitamin D deficiency is more frequently
      encountered than expected in Mediterranean countries, which are sunny most of the
      time. Our country is one of these sunny countries and here, we investigated the
      effect of outfitting style on bone mineral density (BMD) and plasma vitamin D
      levels in women aged between 30-40 years. METHOD: Eighty women, aged between 30
      and 40 years, were included in the study. They were divided into two groups,
      depending on their dress selection. Group-1 consisted of 40 cases with an open
      clothing style, while the 40 women in group-2, preferred the covered clothing
      style. Women were questioned in terms of the risk factors for osteoporosis.
      Levels of plasma 25(OH)2 vitamin D3 and parathormone (PTH) were tested along with
      routine blood analyses. BMD of Lumbar 1-4, femur neck, trochanter, and Ward's
      triangle were measured. RESULTS: In group-2, number of pregnancies and body mass
      index (BMI) was statistically significantly higher (p < 0.05). When the
      laboratory parameters were compared, in group-2, only levels of plasma 25 (OH)2
      vitamin D3 was significantly lower than group-1 (p < 0.05). There was no
      significant difference among groups in terms of BMD. In group-2, there was a
      positive correlation between BMI and BMD at L1-4, hip, femur neck, and trochanter
      regions (p < 0.01, 0.01, 0.05, and 0.05, respectively). CONCLUSION: Traditional
      clothing style leads to vitamin D deficiency in women. In order to meet vitamin D
      need, the face, arm and leg regions of the body should be exposed to one minimal
      erythemal dose (MED; i.e., slight redness of the skin) of sunlight, at least two
      or three times a week. We believe that these cases should be more closely
      monitored for bone loss, especially during postmenopausal period, which is
      considered as a risky term in terms of osteoporosis development.

PMID- 17225056
TI  - Refractory rapidly progressive Takayasu's arteritis successfully treated with
      surgery.
AB  - We describe a case of a patient with rapidly progressive Takayasu's arteritis
      (TA) refractory to conventional immunosuppressive therapy in whom bypass surgery
      was successfully performed. A 38-year-old woman had 2 years history of symptoms
      of compromised cerebral circulation, severe claudication of upper and lower limbs
      and stenocardial symptoms. Serial arteriography revealed occlusions of the right
      subclavian and right common iliac arteries and later on stenosis of the abdominal
      aorta and complete obliteration of the left subclavian artery. Coronarography did
      not show coronary stenosis. Completely occluded left subclavian artery resulted
      in a characteristic subclavian steal syndrome. Therapy with combined
      immunosuppressants was ineffective, severe ischaemic symptoms related to arterial
      occlusions progressed and surgical intervention was inevitable. She underwent
      aorto-bifemoral and 10 months later left carotid-axillary bypass grafting. The
      ischaemic symptoms were resolved after surgery. At 3 years follow-up, the patient
      remained asymptomatic with no evidence of restenosis. This case indicates that
      patients with progressive TA with no improvement while on conventional
      immunosuppressive therapy could have satisfactory outcome and excellent long-term
      clinical remission after multiple arterial bypass grafting.

PMID- 17225055
TI  - Inflammatory synovitis due to underlying lipoma arborescens (gadolinium-enhanced
      MRI features): report of two cases.
AB  - Lipoma arborescens (synovial lipomatosis) is a rare, benign intra-articular
      lesion of unknown etiology. It is a very rare primary benign tumour of the
      synovium, which usually affects the knee joint and can lead to slowly progressive
      chronically swollen knee. In this report we described two cases with this rare
      entity with initial presentation of inflammatory synovitis. We also described the
      Gadolinium (Gd-DTPA)-enhanced MRI features. To the best of our knowledge, this is
      the first report that described inflammatory synovitis in association with this
      rare entity.

PMID- 17225057
TI  - Orofacial dystonia related to Sjogren's syndrome.
AB  - Sjogren's syndrome (SS), either primary or secondary, is rarely accompanied by
      CNS complications. We report the exceptional case of a patient with secondary SS,
      who presented orofacial dystonia as a consequence of her disease. Initial
      treatment with clonazepam and levetiracetam was unsuccessful. However, dystonia
      was dramatically improved by a treatment with corticosteroids. This case
      demonstrates that corticosteroids can be efficacious in the treatment of dystonia
      related to SS.

PMID- 17225058
TI  - Tumor-induced osteomalacia.
AB  - Tumor-induced osteomalacia, also known as oncogenic osteomalacia, is a rare
      paraneoplastic syndrome in which vitamin D resistant osteomalacia occurs due to
      the presence of a tumor. The following case report describes a young woman who
      seeks a second opinion from a rheumatologist and is found to have oncogenic
      osteomalacia. Not often discussed in the rheumatology literature, oncogenic
      osteomalacia is a rare and interesting disease entity in which diagnosis is often
      more challenging than treatment.

PMID- 17225059
TI  - Treatment of 153 Japanese patients with Q-switched alexandrite laser.
AB  - We have recently used Q-switched alexandrite laser for the treatment of various
      kinds of pigmented skin lesions. We retrospectively compared therapeutic outcomes
      of 153 Japanese patients who consulted our department. This approach was not very
      efficient for nevus spilus/cafe-au-lait spots, which seemed laser-resistant,
      especially when the pigmentation had appeared after 1 year of age, was treated
      after 5 years of age, was located on the face, was oval with a smooth border, and
      the patient was male. This approach was equally effective for senile lentigo,
      nevus of Ota, and Mongolian spots, but less effective for acquired bilateral
      nevus of Ota-like macules. Some patients with sacral Mongolian spots or those
      with light-colored, senile lentigo developed severe post-inflammatory
      hyperpigmentation after treatment. As a whole, good therapeutic outcome was
      achieved after multiple treatment sessions. However, the use of other lasers or
      other treatment modalities should be considered to treat nevus spilus/cafe-au
      lait spots.

PMID- 17225060
TI  - Acne and PDT: new techniques with lasers and light sources.
AB  - Acne vulgaris is one of the most common dermatologic disorders encountered in
      everyday practice. Treatment options for this often psychologically scarring
      disease are numerous and, for many individuals, provide relief from the disorder.
      However, factors such as antibiotic resistance and slow onset of action from many
      topical therapies have led researchers to seek out alternative therapies,
      especially for those suffering from moderate to severe inflammatory acne
      vulgaris. Lasers and light sources are finding increased usage in the treatment
      of inflammatory acne vulgaris. Light sources including blue lights and intense
      pulsed lights are becoming regular additions to routine medical management to
      enhance the therapeutic response. Finally, photodynamic therapy may change many
      of the acne vulgaris paradigms, as its place is being defined in the treatment of
      moderate to severe inflammatory acne vulgaris. More and more clinical trials are
      showing the effectiveness of 5-aminolevulinic acid and photodynamic therapy in
      the treatment of moderate to severe inflammatory acne vulgaris.

PMID- 17225062
TI  - Metal Ion availability in mitochondria.
AB  - Transition metal ions are required for many aspects of mitochondrial physiology.
      Copper, iron, manganese and zinc are cofactors in metalloenzymes and
      metalloproteins within the organelle. Little is known how cells maintain optimal
      pools of these metal ions for mitochondrial function. This review documents the
      available literature on mitochondrial metal ion pools and protein metallation
      reactions. Upon perturbation in metal pools, mis-metallation reactions do occur.
      Thus, regulation of metal ion accessibility and bioavailability must exist.

PMID- 17225061
TI  - Atx1-like chaperones and their cognate P-type ATPases: copper-binding and
      transfer.
AB  - Copper is an essential yet toxic metal ion. To satisfy cellular requirements,
      while, at the same time, minimizing toxicity, complex systems of copper
      trafficking have evolved in all cell types. The best conserved and most widely
      distributed of these involve Atx1-like chaperones and P(1B)-type ATPase
      transporters. Here, we discuss current understanding of how these chaperones bind
      Cu(I) and transfer it to the Atx1-like N-terminal domains of their cognate
      transporter.

PMID- 17225063
TI  - Bioinformatic analysis of the TonB protein family.
AB  - TonB is a protein prevalent in a large number of Gram-negative bacteria that is
      believed to be responsible for the energy transduction component in the import of
      ferric iron complexes and vitamin B(12) across the outer membrane. We have
      analyzed all the TonB proteins that are currently contained in the Entrez
      database and have identified nine different clusters based on its conserved 90
      residue C-terminal domain amino acid sequence. The vast majority of the proteins
      contained a single predicted cytoplasmic transmembrane domain; however, nine of
      the TonB proteins encompass a approximately 290 amino acid N-terminal extension
      homologous to the MecR1 protein, which is composed of three additional predicted
      transmembrane helices. The periplasmic linker region, which is located between
      the N-terminal domain and the C-terminal domain, is extremely variable both in
      length (22-283 amino acids) and in proline content, indicating that a Pro-rich
      domain is not a required feature for all TonB proteins. The secondary structure
      of the C-terminal domain is found to be well preserved across all families, with
      the most variable region being between the second alpha-helix and the third beta
      strand of the antiparallel beta-sheet. The fourth beta-strand found in the
      solution structure of the Escherichia coli TonB C-terminal domain is not a well
      conserved feature in TonB proteins in most of the clusters. Interestingly,
      several of the TonB proteins contained two C-terminal domains in series. This
      analysis provides a framework for future structure-function studies of TonB, and
      it draws attention to the unusual features of several TonB proteins.

PMID- 17225064
TI  - Ureteral membranous band causing ureteral obstruction after the ureterolithotomy.
AB  - A 45-year-old male admitted to our clinic of symptoms with moderate left flank
      pain and intermittant macroscopic hematuria. During the last 6 months these
      complaints had worsened. He had history of open retroperitoneal ureterolithotomy
      2 years previously for ureteral stone. He was investigated for calculi, infection
      and other urinary abnormalities. Although direct urinary system graphy was
      normal, excretory urography revealed left ureteric obstruction. On ureteroscopy
      membranous band like an ureteral valve causing ureteral obstruction was observed
      and removed with biopsy pens without resection.

PMID- 17225065
TI  - Is there a relationship among age, international index of erectile function,
      international prostate symptom score, and aging males' symptoms score?
AB  - PURPOSE: To investigate the relationship among the International Index of
      Erectile Function (IIEF), International Prostate Symptom Score (IPSS), and Aging
      Males' Symptoms (AMS) scale scores in various age groups of males. PATIENTS AND
      METHODS: A total of 307 male patients enrolled in the study. Mean age was 52.3
      (range 21-77) years. Group 1 consisted of 51 (< or =39 years), Group 2 consisted
      of 160 (40-59 years), and Group 3 consisted of 96 (> or =60 years) patients.
      First five and 15th questions of the IIEF, IPSS, and AMS scale were replied by
      all the patients. The patients were assessed based on the IIEF for erectile
      dysfunction (ED), IPSS for lower urinary tract symptoms (LUTS), and AMS scale for
      Symptomatic Late-Onset Hypogonadism (SLOH). RESULTS: ED, LUTS, and SLOH symptoms
      were detected in 236 (76.8%), 162 (52.8%), and 184 (59.9%) patients. Except for
      total AMS scores, IIEF and IPSS scores were significantly different among the
      groups (p (AMS) = 0.320, p (IIEF) = 0.000, p (IPSS) = 0.000). In the comparisons
      of the IIEF scores between the each group, significant differences were observed
      (p (Group1-Group2) = 0.000, p (Group1-Group3) = 0.000, p (Group2-Group3) =
      0.000). Nevertheless, IPSS score was significantly lower in the patients with age
      < or =39 years than the other age groups (p = 0.000). CONCLUSIONS: In the present
      study, ED ratio and LUTS severity significantly increased in older men. We did
      not find significant relationship between aging and SLOH symptoms. In the light
      of our results, LUTS seems to be an important risk factor on erectile function.

PMID- 17225066
TI  - Pt-based electro-catalytic materials derived from biosorption processes and their
      exploitation in fuel cell technology.
AB  - Yeast-based biomass, immobilised in polyvinyl alcohol (PVA) cryogels, was used as
      a biosorbant material for the recovery of platinum (PtCl (6) (2-) ) from aqueous
      solutions. The resulting biomass-Pt matrices were then employed directly as an
      electro-catalytic anode in a fuel cell configuration to generate electrical
      energy from renewable sources such as glucose and ethanol. We suggest an
      integrated strategy incorporating the derivation of a high-value product from a
      bioremediative process with a view towards producing energy from renewable fuels
      such as glucose and ethanol.

PMID- 17225067
TI  - Reductive transformation of parathion and methyl parathion by Bacillus sp.
AB  - Based on the results of phenotypic features, phylogenetic similarity of 16S rRNA
      gene sequences and BIOLOG test, a soil bacterium was identified as Bacillus sp.
      DM-1. Using either growing cells or a cell-free extract, it transformed parathion
      and methyl parathion to amino derivatives by reducing the nitro group. Pesticide
      transformation by a cell-free extract was specifically inhibited by three
      nitroreductase inhibitors, indicating the presence of nitroreductase activity.
      The nitroreductase activity was NAD(P)H-dependent, O(2)-insensitive, and
      exhibited the substrate specificity for parathion and methyl parathion. Reductive
      transformation significantly decreased the toxicity of pesticides.

PMID- 17225068
TI  - 15N-{1H} NOE experiment at high magnetic field strengths.
AB  - The heteronuclear (15)N-{(1)H} NOE values are typically determined by taking the
      ratio of (15)N signal intensities recorded in the presence and absence of (1)H
      saturation prior to evolution of (15)N magnetization. Since the intensity ratio
      of two independent experiments is taken, complete recovery of (15)N magnetization
      during the scan repetition delay is critical to obtain reliable NOE values.
      Because it may not be practical to wait for the complete recovery of
      magnetization at high magnetic fields, Solomon equations may be used to correct
      measured NOE values. Here, based on experiments and simulations, we show that
      since the cross-correlation between (1)H-(15)N dipole and (15)N chemical shift
      anisotropy becomes significant at high fields for small or deuterated proteins,
      measured NOE values can not be accurately corrected based on the Solomon
      equations. We also discuss ranges of rotational correlation times and proton spin
      flip rate, in which the NOE values can be corrected by the equations.

PMID- 17225069
TI  - The MUMO (minimal under-restraining minimal over-restraining) method for the
      determination of native state ensembles of proteins.
AB  - While reliable procedures for determining the conformations of proteins are
      available, methods for generating ensembles of structures that also reflect their
      flexibility are much less well established. Here we present a systematic
      assessment of the ability of ensemble-averaged molecular dynamics simulations
      with ensemble-averaged NMR restraints to simultaneously reproduce the average
      structure of proteins and their associated dynamics. We discuss the effects that
      under-restraining (overfitting) and over-restraining (underfitting) have on the
      structures generated in ensemble-averaged molecular simulations. We then
      introduce the MUMO (minimal under-restraining minimal over-restraining) method, a
      procedure in which different observables are averaged over a different number of
      molecules. As both over-restraining and under-restraining are significantly
      reduced in the MUMO method, it is possible to generate ensembles of conformations
      that accurately characterize both the structure and the dynamics of native states
      of proteins. The application of the MUMO method to the protein ubiquitin yields a
      high-resolution structural ensemble with an RDC Q-factor of 0.19.

PMID- 17225070
TI  - Marking transgenic Xenopus froglets with passive micro transponders.
AB  - Standard methods to mark Xenopus laevis individuals like tattooing or clipping
      toenails are inappropriate for the fast growing and regenerating small froglets
      and the previously used transponders are too large. In this study we successfully
      adapted micro transponders to tag these animals. Using these new transponders one
      can now tag small froglets directly after metamorphosis, which has not been
      possible previously. This new technique makes the breeding of transgenic frogs
      most efficient, because the frogs do not have to be kept separately and they grow
      much faster when kept together in large containers.

PMID- 17225071
TI  - A transgenic mouse model engineered to investigate human brain-derived
      neurotrophic factor in vivo.
AB  - Brain-derived neurotrophic factor (BDNF) is an attractive component for the
      treatment of various neurodegenerative diseases such as Alzheimer's or
      Parkinson's disease. Innovative non-invasive therapeutic approaches involve
      appropriate pharmacological induction of endogenous BDNF synthesis in brain. A
      transgenic mouse model has been established to study human BDNF gene expression
      and permit the screening of compounds capable of stimulating its activity. A 145
      kb yeast artificial chromosome carrying the human BDNF gene has been engineered
      to produce the transgene which contains the extended BDNF promoter and 3'
      flanking regions and has integrated the enhanced green fluorescent protein (E
      GFP) coding sequence in place of the BDNF coding exon. Five transgenic lines have
      been obtained through microinjection of the YAC into fertilized mouse oocytes.
      From the three lines expressing the transgene, one displays the specific pattern
      of BDNF expression. Faithful tissue-restricted transcription of BDNF 5' exons and
      localization of the fluorescent reporter gene product in the expected brain
      subregions are reported. This line constitutes an exploitable system for
      investigating human BDNF gene regulation in vivo.

PMID- 17225072
TI  - Cholera toxin B protein in transgenic tomato fruit induces systemic immune
      response in mice.
AB  - Cholera toxin B (CTB) subunit is a well-characterized antigen against cholera.
      Transgenic plants can offer an inexpensive and safe source of edible CTB vaccine
      and may be one of the best candidates for the production of plant vaccines. The
      present study aimed to develop transgenic tomato expressing CTB protein,
      especially in the ripening tomato fruit under the control of the tomato fruit
      specific E8 promoter by using Agrobacterium-mediated transformation. Transgenic
      plants were selected using PCR and Southern blot analysis. Exogenous protein
      extracted from leaf, stem, and fruit tissues of transgenic plants was detected by
      ELISA and Western blot analysis, showing specific expression in the ripening
      fruit, with the highest amount of CTB protein being 0.081% of total soluble
      protein. Gavage of mice with ripe transgenic tomato fruits induced both serum and
      mucosal CTB specific antibodies. These results demonstrate the immunogenicity of
      the CTB protein in transgenic tomato and provide a considerable basis for
      exploring the utilization of CTB in the development of tomato-based edible
      vaccine against cholera. The rCTB antigen resulted in much lower antibody titers
      than an equal amount of exogenous CTB in transgenic fruits, suggesting the
      protective effect of the fibrous tissue of the fruit to the exogenous CTB protein
      against the degradation of protease in the digestive tracts of mice.

PMID- 17225074
TI  - Characterizing coral condition using estimates of three-dimensional colony
      surface area.
AB  - Coral reefs provide shoreline protection, biological diversity, fishery harvests,
      and tourism, all values that stem from the physically-complex coral
      infrastructure. Stony corals (scleractinians) construct and maintain the reef
      through deposition of calcium carbonate. Therefore, assessment of coral reefs
      requires at least some measurement endpoints that reflect the biological and
      physical condition of stony corals. Most monitoring programs portray coral
      quantity as live coral cover, which is the two-dimensional proportion of coral
      surface to sea floor viewed from above (planar view). The absence of the third
      dimension, however, limits our ability to characterize coral reef value,
      physiology, health and sustainability. A three-dimensional (3D) approach more
      realistically characterizes coral structure available as community habitat and,
      when combined with estimates of live coral tissue, quantifies the amount of
      living coral available for photosynthesis, growth and reproduction. A rapid coral
      survey procedure that coupled 3D coral quantification with more traditional
      survey measurements was developed and tested in the field. The survey procedure
      relied on only three underwater observations--species identification, colony
      size, and proportion of live tissue--made on each colony in the transect. These
      observations generated a variety of metrics, including several based on 3D colony
      surface area, that are relevant to reef management.

PMID- 17225073
TI  - Global genome expression analysis of rice in response to drought and high
      salinity stresses in shoot, flag leaf, and panicle.
AB  - To elucidate genome-level responses to drought and high-salinity stress in rice,
      a 70 mer oligomer microarray covering 36,926 unique genes or gene models was used
      to profile genome expression changes in rice shoot, flag leaf and panicle under
      drought or high-salinity conditions. While patterns of gene expression in
      response to drought or high-salinity stress within a particular organ type showed
      significant overlap, comparison of expression profiles among different organs
      showed largely organ-specific patterns of regulation. Moreover, both stresses
      appear to alter the expression patterns of a significant number of genes involved
      in transcription and cell signaling in a largely organ-specific manner. The
      promoter regions of genes induced by both stresses or induced by one stress in
      more than one organ types possess relative enrichment of two cis-elements (ABRE
      core and DRE core) known to be associated with water stress. An initial
      computational analysis indicated that novel promoter motifs are present in the
      promoters of genes involved in rehydration after drought. This analysis suggested
      that rice might possess a mechanism that actively detects rehydration and
      facilitates rapid recovery. Overall, our data supports a notion that organ
      specific gene regulation in response to the two abiotic stresses may primarily be
      mediated by organ-specific transcription responses.

PMID- 17225075
TI  - Desorption kinetics of benzene in a sandy soil in the presence of powdered
      activated carbon.
AB  - Desorption kinetics of benzene was investigated with a modified biphasic
      desorption model in a sandy soil with five different powdered activated carbon
      (PAC) contents (0, 1, 2, 5, 10% w/w) as sorbents. Sorption experiments followed
      by series dilution desorption were conducted for each sorbent. Desorption of
      benzene was successively performed at two stages using deionized water and
      hexane. Modeling was performed on both desorption isotherm and desorption rate
      for water-induced desorption to elucidate the presence of sorption-desorption
      hysteresis and biphasic desorption and if present to quantify the desorption
      resistant fraction (q (irr)) and labile fraction (F) of desorption site
      responsible for rapid process. Desorption isotherms revealed that sorption
      desorption exhibited a severe hysteresis with a significant fraction of benzene
      being irreversibly adsorbed onto both pure sand and PAC, and that desorption
      resistant fraction (q (irr)) increased with PAC content. Desorption kinetic
      modeling showed that desorption of benzene was biphasic with much higher (4-40
      times) rate constant for rapid process (k (1)) than that for slow process (k
      (2)), and that the difference in the rate constant increased with PAC content.
      The labile fraction (F) of desorption site showed a decreasing tendency with PAC.
      The experimental results would provide valuable information on remediation
      methods for soils and groundwater contaminated with BTEX.

PMID- 17225076
TI  - Microcosm evaluation of bioaugmentation after field-scale thermal treatment of a
      TCE-contaminated aquifer.
AB  - This paper investigates effects of combining thermal and biological remediation,
      based on laboratory studies of trichloroethene (TCE) degradation. Aquifer
      material was collected 6 months after terminating a full-scale Electrical
      Resistance Heating (ERH), when the site had cooled from approximately 100 degrees
      C to 40 degrees C. The aquifer material was used to construct bioaugmented
      microcosms amended with the mixed anaerobic dechlorinating culture, KB-1(TM), and
      an electron donor (5 mM lactate). Microcosms were bioaugmented during cooling at
      40, 30, 20, and 10 degrees C, as temperatures continually decreased during
      laboratory incubation. Redox conditions were generally methanogenic, and electron
      donors were present to support dechlorination. For microcosms bioaugmented at 10
      degrees C and 20 degrees C, dechlorination stalled at cis-dichloroethene (cDCE)
      and vinyl chloride (VC) 150 days after bioaugmentation. However, within 300 days
      of incubation ethene was produced in the majority of these microcosms. In
      contrast, dechlorination was rapid and complete in microcosms bioaugmented at 30
      degrees C. Microcosms bioaugmented at 40 degrees C also showed rapid
      dechlorination, but stalled at cDCE with partial VC and ethene production, even
      after 150 days of incubation when the temperature had decreased to 10 degrees C.
      These results suggest that sequential bioremediation of TCE is possible in field
      scale thermal treatments after donor addition and bioaugmentation and that the
      optimal bioaugmentation temperature is approximately 30 degrees C. When
      biological and thermal remediations are to be applied at the same location, three
      bioremediation approaches could be considered: (a) treating TCE in perimeter
      areas outside the source zone at temperatures of approximately 30 degrees C; (b)
      polishing TCE concentrations in the original source zone during cooling from
      approximately 30 degrees C to ambient groundwater temperatures; and (c) using
      bioremediation in downgradient areas taking advantages of the higher temperature
      and potential release of organic matter.

PMID- 17225077
TI  - Pathophysiological aspects of cyclophosphamide and ifosfamide induced hemorrhagic
      cystitis; implication of reactive oxygen and nitrogen species as well as PARP
      activation.
AB  - Cyclophosphamide (CP) and ifosfamide (IF) are widely used antineoplastic agents,
      but their side-effect of hemorrhagic cystitis (HC) is still encountered as an
      important problem. Acrolein is the main molecule responsible of this side-effect
      and mesna (2-mercaptoethane sulfonate) is the commonly used preventive agent.
      Mesna binds acrolein and prevent its direct contact with uroepithelium. Current
      knowledge provides information about the pathophysiological mechanism of HC:
      several transcription factors and cytokines, free radicals and non-radical
      reactive molecules, as well as poly(adenosine diphosphate-ribose) polymerase
      (PARP) activation are now known to take part in its pathogenesis. There is no
      doubt that HC is an inflammatory process, including when caused by CP. Thus, many
      cytokines such as tumor necrosis factor (TNF) and the interleukin (IL) family and
      transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator
      protein-1 (AP-1) also play a role in its pathogenesis. When these molecular
      factors are taken into account, pathogenesis of CP-induced bladder toxicity can
      be summarized in three steps: (1) acrolein rapidly enters into the uroepithelial
      cells; (2) it then activates intracellular reactive oxygen species and nitric
      oxide production (directly or through NF-kappaB and AP-1) leading to
      peroxynitrite production; (3) finally, the increased peroxynitrite level damages
      lipids (lipid peroxidation), proteins (protein oxidation) and DNA (strand breaks)
      leading to activation of PARP, a DNA repair enzyme. DNA damage causes PARP
      overactivation, resulting in the depletion of oxidized nicotinamide-adenine
      dinucleotide and adenosine triphosphate, and consequently in necrotic cell death.
      For more effective prevention against HC, all pathophysiological mechanisms must
      be taken into consideration.

PMID- 17225078
TI  - Phytoseiulus persimilis response to herbivore-induced plant volatiles as a
      function of mite-days.
AB  - The predatory mite, Phytoseiulus persimilis (Acari: Phytoseiidae), uses plant
      volatiles (i.e., airborne chemicals) triggered by feeding of their herbivorous
      prey, Tetranychus urticae (Acari: Tetranychidae), to help locate prey patches.
      The olfactory response of P. persimilis to prey-infested plants varies in direct
      relation to the population growth pattern of T. urticae on the plant; P.
      persimilis responds to plants until the spider mite population feeding on a plant
      collapses, after which infested plants do not attract predators. It has been
      suggested that this represents an early enemy-free period for T. urticae before
      the next generation of females is produced. We hypothesize that the mechanism
      behind the diminished response of predators is due to extensive leaf damage
      caused by T. urticae feeding, which reduces the production of volatiles
      irrespective of the collapse of T. urticae population on the plant. To test this
      hypothesis we investigated how the response of P. persimilis to prey-infested
      plants is affected by: 1) initial density of T. urticae, 2) duration of
      infestation, and 3) corresponding leaf damage due to T. urticae feeding.
      Specifically, we assessed the response of P. persimilis to plants infested with
      two T. urticae densities (20 or 40 per plant) after 2, 4, 6, 8, 10, 12 or 14
      days. We also measured leaf damage on these plants. We found that predator
      response to T. urticae-infested plants can be quantified as a function of mite
      days, which is a cumulative measure of the standing adult female mite population
      sampled and summed over time. That is, response to volatiles increased with
      increasing numbers of T. urticae per plant or with the length of time plant was
      infested by T. urticae, at least as long at the leaves were green. Predatory
      mites were significantly attracted to plants that were infested for 2 days with
      only 20 spider mites. This suggests that the enemy-free period might only provide
      a limited window of opportunity for T. urticae because relatively low numbers of
      T. urticae per plant can attract predators. Leaf damage also increased as a
      function of mite-days until the entire leaf was blanched. T. urticae populations
      decreased at this time, but predator response to volatiles dropped before the
      entire leaf was blanched and before the T. urticae population decreased. This
      result supports our hypothesis that predator response to plant volatiles is
      linked to and limited by the degree of leaf damage, and that the quantitative
      response to T. urticae populations occurs only within a range when plant quality
      has not been severely compromised.

PMID- 17225080
TI  - Alterations in coagulation profiles and biochemical and haematological parameters
      in cattle with traumatic reticuloperitonitis.
AB  - This study was designed to investigate alterations in coagulation, and in
      biochemical and haematological parameters in cattle with traumatic
      reticuloperitonitis (TRP). In the study, 28 dairy cattle with TRP and 10
      clinically healthy cattle (control) of different ages and breeds were used.
      Cattle with TRP had prolonged prothrombin time (PT), thrombin time (TT) and
      activated partial thromboplastin time (APTT). Erythrocytopenia, thrombocytopenia
      and hyperfibrinogenaemia were detected in animals with TRP. Furthermore, the
      serum concentrations of total protein, globulin and total bilirubin, and the
      activities of alkaline phosphatase (ALP) and aspartate aminotransferase (AST)
      were also high in cattle with TRP compared to those of the control group. The
      serum concentrations of calcium were significantly low in the TRP group. The
      results of this study, therefore, indicate that TRP causes significant
      coagulation abnormalities and biochemical and haematological alterations in dairy
      cattle.

PMID- 17225079
TI  - Rickettsial pathogens in the tropical rat mite Ornithonyssus bacoti (Acari:
      Macronyssidae) from Egyptian rats (Rattus spp.).
AB  - We collected and tested 616 tropical rat mites (Ornithonyssus bacoti (Hirst))
      from rats (Rattus norvegicus (Berkenhout) and R. rattus (Linnaeus)) throughout 14
      governorates in Egypt and tested DNA extracts from pools of these mites for
      Bartonella spp., Coxiella burnetii, and Rickettsia spp. by PCR amplification and
      sequencing. Three different mite-associated bacterial agents, including one
      Bartonella and two Rickettsia spp., were detected in eight pools of mites.
      Further research could demonstrate the vector potential of mites and
      pathogenicity of these agents to humans or animals.

PMID- 17225081
TI  - Occurrence of Cryptosporidium parvum and bacterial pathogens in faecal material
      in the red fox (Vulpes vulpes) population.

PMID- 17225082
TI  - Development of indirect enzyme-linked immunosorbent assay with nucleoprotein as
      antigen for detection and quantification of antibodies against avian influenza
      virus.
AB  - Avian influenza (AI) is a serious infectious disease caused by avian influenza
      virus (AIV) belonging to type A Orthomyxovirus. In the present study, we
      developed an indirect enzyme-linked immunosorbent assay (ELISA) employing E. coli
      expressed full-length nucleoprotein (NP) of H9N2 avian influenza virus for the
      detection and quantification of antibodies against AIV nucleoprotein. The NP
      ELISA was compared with the AI agar gel propagation (AGP) test, haemagglutination
      inhibition (HI) test, and IDEXX-FlockChek ELISA using 263 sera. The NP-ELISA was
      significantly more sensitive than the AGP and HI tests, and showed 96.2%
      agreement ratio with IDEXX-FlockChek ELISA. With results obtained using the NP
      ELISA, an ELISA titre (ET) prediction equation, with which the ELISA titres of a
      flock or individual chickens can be determined, was derived from a
      positive/negative (P/N) ratio standard curve. The NP-ELISA enables an alternative
      rapid serological diagnosis and is suitable for influenza A antibody screening,
      especially in species that harbour several influenza subtypes.

PMID- 17225083
TI  - Pharmacokinetic profile of erythromycin after intramammary administration in
      lactating dairy cows with specific mastitis.
AB  - The pharmacokinetics of erythromycin was studied in five lactating dairy cows
      following single intramammary infusion of 300 mg erythromycin in each of two
      quarters per cow with specific mastitis. Levels of erythromycin in plasma and
      quarter milk samples were measured by agar plate diffusion assay using
      Micrococcus luteus (ATCC 9341) as the test organism. Erythromycin level in plasma
      reached a peak concentration value (C(max)) of 0.07 +/- 0.01 microg/ml at 30 min;
      thereafter, levels declined gradually to reach 0.05 +/- 0.00 microg/ml 12 h post
      drug administration. The pharmacokinetic profile of the drug revealed mean
      absorption half life (t(1/2 ka)) as 0.26 +/- 0.05 h. The drug was eliminated
      slowly with elimination half-life (t(1/2 beta)) of 13.75 +/- 0.35 h and
      elimination rate constant (k(el)) of 0.04 +/- 0.00 h(-1). The volume of
      distribution based on the zero-time plasma concentration intercept of the least
      squares regression line of the elimination phase (V(d(B))) was 0.032 L/kg. The
      drug crossed to untreated quarters also; mean drug levels of 0.20 +/- 0.07, 0.23
      +/- 0.07, 0.17 +/- 0.04, and 0.17 +/- 0.04 microg/ml were found at 3, 6, 8 and 12
      h, respectively. The mean drug concentration for treated quarters was measured as
      22.97 +/- 2.31 microg/ml milk at first milking (12 h) following drug infusion. No
      apparent adverse reaction was seen in cows administered erythromycin. It is
      concluded that following intramammary infusion erythromycin diffuses readily and
      extensively in various body fluids and tissues and adequate concentration is
      maintained in udder tissues for at least 12 h post intramammary administration.
      Thus, erythromycin may be recommended for local therapy of acute mastitis caused
      by Gram-positive bacteria in lactating dairy cows.

PMID- 17225084
TI  - Development of a simple enzyme immunoassay for the determination of ovine
      luteinizing hormone.
AB  - The present study describes the development and validation of a simple sensitive
      and specific sandwich enzyme immunoassay (EIA) for the quantification of ovine
      luteinizing hormone (LH) in plasma. Microtitre plates were coated with the
      capture antibody 518b7 anti-bovine LH. A second peroxidase-labelled anti-ovine LH
      antibody was used as tracer. A simple 3-step procedure was used for the sample
      analysis; (1) incubation of standards and samples with the pre-coated antibody
      plates for 2 h at 37 degrees C; (2) incubation with the peroxidase-labelled
      antibody for 1 h at room temperature; and (3) colour development with TMB
      substrate. A linear dose-response curve was obtained in the range 0-10 ng/ml (r2
      > 0.99). The detection limit was 0.05 ng/ml, and the intra-assay and inter-assay
      coefficients of variation were 7% and 11.7%, respectively. The theoretical
      stability of microplates and reagents was calculated, this being greater than one
      year. Low or undetectable cross-reactivities were recorded for follicle
      stimulating hormone, bovine thyroid-stimulating hormone, equine chorionic
      gonadotrophin and a gonadotrophin-releasing hormone (GnRH) analogue. The EIA was
      biologically validated by the determination of plasma LH concentrations of nine
      Rasa Aragonesa ovariectomized and estradiol-implanted ewes after a double GnRH
      challenge. In conclusion, this enzyme immunoassay provides an efficient, simple
      and sensitive method for the routine analysis of ovine LH.

PMID- 17225085
TI  - Immunogenicity of empty capsids of porcine circovius type 2 produced in insect
      cells.
AB  - Porcine circovirus type 2 (PCV2), a single-stranded DNA virus, is associated with
      postweaning multisystemic wasting syndrome (PMWS). ORF2 protein (capsid) of PCV2
      was recently demonstrated to be a major immunogenable to induce protection in
      pigs with a prime-boost protocol. In this study, the ORF2 gene of PCV2 was
      expressed in insect cells. The product self-assembled into particles that were
      structurally and antigenically indistinguishable from regular PCV2 capsids. To
      evaluated the immunogenicity of these virus-like particles, PCV2-free piglets
      were vaccinated with the crude lysate from recombinant baculovirus (Ac.ORF2)
      infected insect cells, at doses of 0.1 ml (10(6) cells), 0.5 mL (5 x 10(6) cells)
      or 1.0 ml (10(7) cells). The immune response was monitored by an indirect enzyme
      linked immunosorbent assay (ELISA) for PCV2 antibody and lymphocyte proliferation
      assay. The ELISA results indicated that primary immune response was elicited with
      0.5 ml or 1.0 ml of crude lysate from Ac.ORF2. After boost immunization,
      relatively higher levels of PCV2 antibody were elicited in 0.5-ml or 1.0-ml
      vaccinated groups, compared to the 0.1-ml group. In addition, higher PCV2
      specific lymphocyte proliferation response was developed in piglets vaccinated
      with 0.5 ml or 1.0 ml of crude lysate, especially in those vaccinated with with
      1.0 ml of crude lysate. Thus, the expressed ORF2 protein has significant
      potential as a subunit vaccine against PCV2 infection.

PMID- 17225086
TI  - Genogrouping of vaccine breakdown strains (VBS) of feline calicivirus in Japan.
AB  - Although prevention of feline calcivirus (FCV) infection by vaccination has been
      attempted, and isolation of FCV, development of the disease, and a few fatal
      cases in vaccinated cats have been reported. Fifteen FCV strains isolated from
      cats that had been vaccinated with commercially available FCV vaccines (F9, FCV
      255, and FC-7) were genogrouped. Molecular analysis of viral genomes involved the
      construction of a phylogenetic tree of capsid genes using the NJ method. Cat anti
      F9 serum and rabbit anti-FCV-255 serum were used for virus neutralization tests.
      Molecular phylogenetic analysis of the amino acid sequences of 15 virus isolates
      and those of the previously published and GenBank-deposited 9 global and 14
      Japanese strains showed that 8 (53%) of the 15 virus isolates as well as the
      vaccine strains F9 and FCV-255 belonged to genogroup I (G(A)I), and 7 (47%)
      belonged to genogroup II (G(A)II). Of the 8 G(A)I strains, 2 were isolated from
      cats that had been vaccinated with an F9 strain live vaccine, 5 from cats
      vaccinated with an FCV-255-derived vaccine, and 1 from a cat vaccinated with an
      FC-7-derived vaccine. Of the 7 GAll strains, 5 were isolated from cats that had
      been vaccinated with the F9 strain live vaccine, 1 from a cat vaccinated with the
      FCV-255-derived vaccine, and 1 from a cat vaccinated with the FC-7-derived
      vaccine. These results indicate that more vaccine breakdown strains isolated from
      the cats vaccinated with the F9 strain-derived vaccine belong to G(A)II than to
      G(A)I, whereas more vaccine breakdown strains isolated from the cats vaccinated
      with the FCV-255 strain-derived vaccine belong to G(A)I than to G(A)II, and that
      when the FC-7 strain-derived vaccine is used, the vaccine breakdown strains
      belong almost equally to G(A)I and G(A)II. Thus, the genogroups of virus isolates
      varied with the vaccine strain used (p < 0.05). On the other hand, the
      neutralizing titres of feline anti-F9 serum and rabbit anti-FCV-255 serum against
      the 15 isolates were very low, showing no relationships between neutralizing
      antibody titres and genogroups. The DNA sequence identities between the virus
      isolates and the vaccine strains were low, at 70.6-82.9%, and no strains were
      found to have sequences derived from the vaccine strains. Alignment of amino acid
      sequences showed that the G(A)I or G(A)II virus isolates from the F9-vaccinated
      cats differed at position 428 of the 5' hypervariable region (HVR) of capsid
      region of the F9 strain, whereas those from the FCV-255-vaccinated cats differed
      at positions 438, 453, and 460 of the 5'HVR of capsid region E of the F9 strain.
      We speculate that these differences influence genogrouping. The amino acid
      changes within the F9 linear epitopes common to G(A)I and G(A)II were noted at
      positions 450, 451, 457 of 5'HVR of the capsid region E in the isolates from F9
      derived vaccine-treated cats, and 449, 450, and 451 of 5'HVR of capsid region E
      in the isolates from FCV-255-derived vaccine-treated cats, suggesting that these
      amino acid changes are involved in escapes. These results suggest that alternate
      vaccination with the F9 and FCV-255 strains or the use of a polyvalent vaccine
      containing GAll strains serves to inhibit development.

PMID- 17225088
TI  - Influence of slaughtering method on some aspects of quality of gilthead seabream
      and smoked rainbow trout.
AB  - The effects of several slaughter methods on the quality of fresh and smoked trout
      and fresh gilthead seabream were evaluated during storage at 2 degrees C.
      Electrically stunned trout had slower ATP depletion of raw muscle and lower lipid
      oxidation in smoked product during storage. Gilthead seabream immersed in an ice
      slurry (IS group) after the harvest showed a more regular ATP depletion than in
      fish exposed to CO2. Nevertheless, in the case of the IS group, self-initiated
      behaviour, response to handling and breathing all ceased only after 15-20 min,
      whereas carbon dioxide-stunned fish appeared dead after 5 min. However, gilthead
      seabream group having slower ATP depletion also showed lower lipid oxidation of
      muscle during storage. In both species this could be due to the rapid conversion
      of xanthine dehydrogenase to xanthine oxidase induced by the rapid consumption of
      ATP. Xanthine oxidase, in the presence of redox iron and reintroduced oxygen, can
      produce hydrogen peroxide and, consequently, hydroxyl radicals.

PMID- 17225087
TI  - Ischaemia/reperfusion injury in experimentally induced abomasal volvulus in
      sheep.
AB  - The purpose of the study was to evaluate ischaemia/reperfusion injury in
      simulated abomasal volvulus in sheep. Sixteen ewes were randomly allocated to
      three groups. The control group (n=4) served as sham-operated controls. The
      animals of the ischaemia group and reperfusion group (n=6, each) underwent a
      simulated 'abomasal volvulus'. The abomasum was exteriorized under general
      inhalation anesthesia and forced into a 180( composite function) anticlockwise
      rotation around its longitudinal axis, followed by another 270( composite
      function) anticlockwise rotation around its transectional axis. All ewes were
      monitored for 4 h. In the reperfusion group, volvulus was released after 3 h
      (i.e., 1 h of reperfusion). In the ischaemia group, the volvulus remained for 4 h
      (no reperfusion). Vital signs were monitored and some haematological and
      biochemical parameters were measured, without any significant differences. Full
      section biopsy specimens were taken at the 3rd and 4th hours from the greater
      curvature of the abomasum. Histopathological lesions were scored according to the
      severity of mucosal oedema, submucosal oedema, haemorrhage submucosal and
      submuscularis layers, and polymorphonuclear infiltration on a scale of 0 to 4
      (nil, mild, moderate, severe, and extreme). Another biopsy specimen was taken at
      the 4th hour for transmission electron microscopic examination. The scored
      lesions in light-microscopic examination were significantly different at the 3rd
      and 4th hours between the control and the experimental groups (p<0.05). There was
      no significant difference between the reperfusion and ischaemia groups (p>0.1).
      Within-group comparisons (3rd hour with 4th hour) revealed no significant
      differences. In transmission electron microscopic examination there were no
      remarkable changes in the control group, but in the ischaemia and reperfusion
      groups there were remarkable cellular (epithelial and goblet cells),
      mitochondrial and microvillous changes that strongly implied the occurrence of
      ischaemia (p<0.05). In transmission electron-microscopic examination of abomasal
      samples the lesions were more remarkable in reperfusion group than in the
      ischaemia group. It is concluded that ischaemia/reperfusion injury occurred in
      this model of simulated abomasal volvulus in sheep and that ischaemia/reperfusion
      injury should be considered as a potential determining factor in the outcome of
      cattle with abomasal volvulus.

PMID- 17225089
TI  - Pharmacokinetics of tilmicosin (Provitil powder and Pulmotil liquid AC) oral
      formulations in chickens.
AB  - A bioavailability and pharmacokinetics study of powder and liquid tilmicosin
      formulations was carried out in 18 healthy chickens according to a single-dose,
      two-period, two-sequence, crossover randomized design. The two formulations were
      Provitil and Pulmotil AC. Both drugs were administered to each chicken after an
      overnight fast on two treatment days separated by a 2-week washout period. A
      modified rapid and sensitive HPLC method was used for determination of tilmicosin
      concentrations in chicken plasma. Various pharmacokinetic parameters including
      area under plasma concentration-time curve (AUC(0-72)), maximum plasma
      concentration (C(max)), time to peak concentration (t(max)), elimination half
      life (t(1/2beta)), elimination rate (k(el)), clearance (Cl(B)), mean residence
      time (MRT) and volume of distribution (V(d,area)) were determined for both
      formulations. The average means of AUC(0-72) for Provitil and Pulmotil AC were
      very close (24.24 +/- 3.86, 21.82 +/- 3.14 (microg x h)/ml, respectively), with
      no significant differences based on ANOVA. The relative bioavailability of
      Provitil as compared to Pulmotil AC was 111%. In addition, there were no
      significant differences in the C(max) (2.09 +/- 0.37, 2.12 +/- 0.40 microg/ml),
      tmax (3.99 +/- 0.84, 5.82 +/- 1.04 h), t(1/2beta) (47.4 +/- 9.32, 45.0 +/- 5.73
      h), k(el) (0.021 +/- 0.0037, 0.022 +/- 0.0038 h(-1)), Cl(B) (19.73 +/- 3.73,
      21.37 +/- 4.54ml/(min/kg)), MRT (71.20 +/- 12.87, 67.15 +/- 9.01 h) and V(d,area)
      (1024.8 +/- 87.5, 1009.8 +/- 79.5 ml/kg) between Pulmotil AC and Provitil,
      respectively. In conclusion, tilmicosin was rapidly absorbed and slowly
      eliminated after oral administration of single dose of tilmicosin aqueous and
      powder formulations. Provitil and Pulmotil AC can be used as interchangeable
      therapeutic agents.

PMID- 17225090
TI  - Ginkgolides protect primary cortical neurons from potassium cyanide-induced
      hypoxic injury.
AB  - In this study, we investigated the effects of ginkgolides (Gins A, B, C and J),
      the main constituent of the non-flavone fraction of EGb 761, on hypoxic injury
      induced by potassium cyanide (KCN) in primary cortical neurons. The neurons were
      pretreated with or without ginkgolides for 24 h before incubation with KCN for 4
      h. Cell viability was then determined by a MTT (3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyletrazolium bromide] assay and lactate dehydrogenase (LDH) release from
      neurons into the medium was measured. The morphological changes of neurons were
      observed under inverse microscopy and electron microscopy. The results
      demonstrated that KCN (0.05 mmol/l) significantly decreased cell viability and
      increased LDH release (P < 0.05 versus the control). The characteristic changes
      of neuronal morphology induced by KCN were observed. However, pretreatment of
      neurons with 37.5 microg/ml of ginkgolides (ginkgolides + KCN group) led to a
      significant increase in cell viability, a decrease in LDH release (P < 0.05
      versus the KCN group) and a remarkable improvement in cellular morphology in
      hypoxic neurons compared with the KCN group. The data suggested that ginkgolides
      have a significant role to protect the primary cortical neurons from hypoxic
      injury induced by KCN.

PMID- 17225091
TI  - Optimal integration of shape information from vision and touch.
AB  - Many tasks can be carried out by using several sources of information. For
      example, an object's size and shape can be judged based on visual as well as
      haptic cues. It has been shown recently that human observers integrate visual and
      haptic size information in a statistically optimal fashion, in the sense that the
      integrated estimate is most reliable (Ernst and Banks in Nature 415:429-433,
      2002). In the present study, we tested whether this holds also for visual and
      haptic shape information. In previous studies virtual stimuli were used to test
      for optimality in integration. Virtual displays may, however, contain additional
      inappropriate cues that provide conflicting information and thus affect cue
      integration. Therefore, we studied optimal integration using real objects.
      Furthermore, we presented visual information via mirrors to create a spatial
      separation between visual and haptic cues while observers saw their hand touching
      the object and thus, knew that they were seeing and feeling the same object. Does
      this knowledge promote integration even though signals are spatially discrepant
      which has been shown to lead to a breakdown of integration (Gepshtein et al. in J
      Vis 5:1013-1023, 2005)? Consistent with the model predictions, observers weighted
      visual and haptic cues to shape according to their reliability: progressively
      more weight was given to haptics when visual information became less reliable.
      Moreover, the integrated visual-haptic estimate was more reliable than either
      unimodal estimate. These findings suggest that observers integrate visual and
      haptic shape information of real 3D objects. Thereby, knowledge that multisensory
      signals arise from the same object seems to promote integration.

PMID- 17225092
TI  - Synergistic effects of Lactobacillus rhamnosus ZDY114 and bovine colostrums on
      the immunological function of mouse in vivo and in vitro.
AB  - The synergistic effects of Lactobacillus rhamnosus and bovine colostrums on the
      immunity of mice in vivo and in vitro were investigated. Eight- to ten-week-old
      mice were used for two series experiments; one part of mice were
      immunocompromised by intraperitoneal injections of cyclophosphamide. In series I,
      immunocompromised mice were continuously fed with diet A (L. rhamnosus ZDY114 5 x
      10(7) CFU/kg), B (bovine colostrums 0.5 g/kg), C (combination of diet A and B),
      and D (sterile saline) for 4 weeks and killed. Thereof, phagocytosis ratio and
      index of macrophage to chicken red blood cells in abdominal cavity and lymphocyte
      transformation rate were determined. In series II, both normal and
      immunocompromised mice were used to investigate the in vitro stimulation of
      lymphocyte proliferation by substances from the overnight culture of L. rhamnosus
      ZDY114 by the MTT colorimetric method. Compared with diet D, in the diet A, B,
      and C groups, the phagocytosis ratio of macrophages increased by 1.63, 1.54, and
      2.3-fold, respectively, and the lymphocyte transformation ratio by 1.78, 2.08,
      and 2.35-fold, respectively. In vitro test with MTT showed that 3, 10, 50 kD
      substances from the overnight culture of L. rhamnosus ZDY114 significantly
      increased the growth of lymphocyte by 1.63, 1.53, and 1.34-fold, respectively. In
      conclusion, L. rhamnosus and bovine colostrums can enhance the functions of
      immune system supported by lymphocytes and peritoneal macrophages either in vivo
      or in vitro.

PMID- 17225093
TI  - Development of recombinant Aspergillus oryzae whole-cell biocatalyst expressing
      lipase-encoding gene from Candida antarctica.
AB  - To expand the industrial applications of Candida antarctica lipase B (CALB), we
      developed Aspergillus oryzae whole-cell biocatalyst expressing the lipase
      encoding gene from C. antarctica. A. oryzae niaD300, which was derived from the
      wild type strain RIB40, was used as the host strain. The CALB gene was isolated
      from C. antarctica CBS6678 and expression plasmids were constructed with and
      without secretion signal peptide. The lipase gene was expressed under the control
      of improved glaA and pNo-8142 promoters of plasmids pNGA142 and pNAN8142,
      respectively. The Southern blot analysis demonstrated the successful integration
      of the CALB gene in the genome of A. oryzae. To determine the role of signal
      peptide, the expression plasmids were constructed with homologous and
      heterologous secretion signal sequences of triacylglycerol lipase gene (tglA)
      from A. oryzae and lipase B (CALB) from C. antarctica, respectively. The C
      terminal FLAG tag does not alter the catalytic properties of the lipase enzyme
      and Western blotting analysis using anti-FLAG antibodies demonstrated the
      presence of cell wall and membrane bound lipase responsible for the biocatalytic
      activity of the whole-cell biocatalyst. The resultant recombinant A. oryzae was
      immobilized within biomass support particles (BSPs) made of polyurethane foam
      (PUF) and the BSPs were successfully used for the hydrolysis of para-nitrophenol
      butyrate (p-NPB) and for the optical resolution of (RS)-1-phenyl ethanol by
      enantioselective transesterification with vinyl acetate as acyl donor.

PMID- 17225094
TI  - Recombinant therapeutic antibodies.
AB  - Recombinant antibody technology has revolutionized the development of antibody
      therapeutics. This minireview offers an overview of enabling technologies and
      future prospects of this rapidly progressing field.

PMID- 17225095
TI  - Secretory expression of a heterologous nattokinase in Lactococcus lactis.
AB  - Nattokinase has been reported as an oral health product for the prevention of
      atherosclerosis. We developed a novel strategy to express a nattokinase from
      Bacillus subtilis in a live delivery vehicle, Lactococcus lactis. Promoter P(
      nisZ) and signal peptide SP(Usp) were used for inducible and secretory expression
      of nattokinase in L. lactis. Western blotting analysis demonstrated that
      nattokinase was successfully expressed, and about 94% of the enzyme was secreted
      to the culture. The recombinant nattokinase showed potent fibrinolytic activity,
      equivalent to 41.7 urokinase units per milliliter culture. Expression and
      delivery of such a fibrinolytic enzyme in the food-grade vehicle L. lactis would
      facilitate the widespread application of nattokinase in the control and
      prevention of thrombosis diseases.

PMID- 17225096
TI  - Dose-response relationships and statistical performance of a battery of bacterial
      gene profiling assays.
AB  - Because of increasing awareness and legislative demands, there is a demand for
      the development and use of biological assays for the assessment of the toxicity
      of chemicals, environmental samples. Recently, a growing number of bacterial
      reporter assays have been developed and implemented. Nevertheless, little data is
      published on the performance of these assays in terms of analytical parameters.
      We present results on a battery of 14 transgenic Escherichia coli strains
      carrying different promoter::reporter fusions. Growth characteristics and basal
      expression levels were modeled and fitted, data show that growth curves should be
      taken into account during test development. Our study shows that the induction
      profiles reflect the mode of action, e.g., paraquat clearly induces the soxRS
      operon. The sensitivity of the assay compares well to that of whole organism
      tests, e.g., fish and Daphnia for polar organics. Metal toxicity is detected less
      efficiently, e.g., cadmium is detected near the LC50 of carp, considered a
      relatively insensitive species towards cadmium. The assay variability ranges from
      10 to 40% depending on the strain, comparable to that of other bioassays. The
      variability was shown to be determined by the intrinsic traits of the promoter
      strain combination, not by operating conditions.

PMID- 17225097
TI  - Ergosterol production from molasses by genetically modified Saccharomyces
      cerevisiae.
AB  - Ergosterol is an economically important metabolite produced by fungi. Recombinant
      Saccharomyces cerevisiae YEH56(pHXA42) with increased capacity of ergosterol
      formation was constructed by combined overexpression of sterol C-24(28) reductase
      and sterol acyltransferase in the yeast strain YEH56. The production of
      ergosterol by this recombinant strain using cane molasses (CM) as an inexpensive
      carbon source was investigated. An ergosterol content of 52.6 mg/g was obtained
      with 6.1 g/l of biomass from CM medium containing 60 g/l of total sugar in 30 h
      in shake flask. The ergosterol yield was enhanced through the increasing cell
      biomass by supplementation of urea to a concentration of 6 g/l in molasses
      medium. Fermentation was performed in 5-l bioreactor using the optimized molasses
      medium. In batch fermentation, the effect of agitation velocity on ergosterol
      production was examined. The highest ergosterol yield was obtained at 400 rpm
      that increased 60.4 mg/l in comparison with the shake flask culture. In fed-batch
      fermentation, yeast cells were cultivated, firstly, in the starting medium
      containing molasses with 20 g/l of total sugar, 1.68 g/l of phosphate acid, and 6
      g/l of urea (pH 5.4) for 5 h, then molasses containing 350 g/l of total sugar was
      fed exponentially into the bioreactor to keep the ethanol level in the broth
      below 0.5%. After 40 h of cultivation, the ergosterol yield reached 1,707 mg/l,
      which was 3.1-fold of that in the batch fermentation.

PMID- 17225098
TI  - Multimerization and fusion expression of bovine lactoferricin derivative LfcinB15
      W4,10 in Escherichia coli.
AB  - Antimicrobial peptides are promising candidates for therapeutic and industrial
      application owing to their broad spectrum. In this work, a cost-effective method
      for expression of a potent antimicrobial peptide, bovine lactoferricin derivative
      LfcinB15-W4,10, has been developed. The oligonucleotide encoding the peptide was
      linked to generate different oligomeric oligonucleotide segments containing from
      one to nine but eight tandem copies which was inserted individually to the E.
      coli expression vector pET32a. The thioredoxin fusion peptides were successfully
      expressed and detected with different molecular weight on SDS gel, respectively.
      Among the monomer and other multimeric peptides, the tetramer was expressed at
      the highest level. After purification, more than 10 mg of tetramer with 99%
      purity was obtained from 1 l culture and exhibited similar antimicrobial activity
      as synthetic LfcinB15-W4,10 monomer. The expression system in this study provides
      a potential production method for lactoferricin derivatives and other
      antimicrobial peptides in research and industrial applications.

PMID- 17225099
TI  - Cellulose biosynthesis pathway is a potential target in the improved treatment of
      Acanthamoeba keratitis.
AB  - Acanthamoeba is an opportunistic protozoan pathogen that can cause blinding
      keratitis as well as fatal granulomatous encephalitis. One of the distressing
      aspects in combating Acanthamoeba infections is the prolonged and problematic
      treatment. For example, current treatment against Acanthamoeba keratitis requires
      early diagnosis followed by hourly topical application of a mixture of drugs that
      can last up to a year. The aggressive and prolonged management is due to the
      ability of Acanthamoeba to rapidly adapt to harsh conditions and switch
      phenotypes into a resistant cyst form. One possibility of improving the treatment
      of Acanthamoeba infections is to inhibit the ability of these parasites to switch
      into the cyst form. The cyst wall is partially made of cellulose. Here, we tested
      whether a cellulose synthesis inhibitor, 2,6-dichlorobenzonitrile (DCB), can
      enhance the effects of the antiamoebic drug pentamidine isethionate (PMD). Our
      findings revealed that DCB can block Acanthamoeba encystment and may improve the
      antiamoebic effects of PMD. Using in vitro assays, the findings revealed that DCB
      enhanced the inhibitory effects of PMD on Acanthamoeba binding to and
      cytotoxicity of the host cells, suggesting the cellulose biosynthesis pathway as
      a novel target for the improved treatment of Acanthamoeba infections.

PMID- 17225100
TI  - Expression of an AT-rich xylanase gene from the anaerobic fungus Orpinomyces sp.
      strain PC-2 in and secretion of the heterologous enzyme by Hypocrea jecorina.
AB  - The catalytic domain encoded by an adenine-thymine (AT)-rich xylanase gene (xynA)
      of the anaerobic fungus Orpinomyces was expressed in Hypocrea jecorina under the
      control of the cel7A promoter and terminator. No XynA protein was detected in H.
      jecorina culture supernatants when the original sequence was fused to the H.
      jecorina cel5A region coding for its signal peptide, carbohydrate-binding module,
      and hinge. Replacing the xynA (56% AT content) with a synthetic sequence
      containing lower AT content (39%) supported the extracellular production (150 mg
      l(-1)) of the fusion xylanase by H. jecorina. Northern analysis revealed that
      successful production after the decrease in AT content was related to higher
      levels of the xylanase-specific mRNA. Another construct with an RDKR-coding
      sequence inserted between the cel5A linker and the xynA catalytic domain allowed
      production of the fully processed active xylanase catalytic domain. Both the
      fusion (40 kDa) and the fully processed (28 kDa) forms displayed enzymatic
      properties of family 11 xylanases. Both the R and the Kex2-like KR sites were
      recognized during secretion, resulting in a mixture of two amino termini for the
      28-kDa xylanase. The work demonstrated for the first time that glycoside
      hydrolases derived from anaerobic fungi can be produced by H. jecorina.

PMID- 17225101
TI  - The Pseudozyma flocculosa actin promoter allows the strong expression of a
      recombinant protein in the Pseudozyma species.
AB  - Fungi belonging to the recently classified genus Pseudozyma possess some unique
      properties such as biocontrol activity, production of rare antimicrobial
      glycolipids and production of recombinant proteins. In this work, we report the
      first cloning of a promoter endogenous to the multi-faceted yeast-like Pseudozyma
      flocculosa, that of the actin gene. The promoter region lacked typical TATA or
      CAAT box but displayed three putative GC box and two CT-rich regions. As in other
      related basidiomycetes, only one copy of the actin gene was present in the genome
      of P. flocculosa. The activity of the actin promoter was compared to that of the
      HSP70 promoter from Ustilago maydis in two Pseudozyma species. In P. flocculosa,
      the actin promoter allowed the expression of a very high amount of GFP protein
      (27.8 mg g(-1) total protein) compared to those obtained with the HSP70 promoter
      in liquid culture. By contrast, the levels of GFP expression obtained in liquid
      culture were similar with the actin or the HSP70 promoter in Pseudozyma
      antarctica. A similar pattern of GFP expression was observed in solid culture.
      The cloning of this new promoter offers a unique genetic tool to further exploit
      and study the unusual properties of fungi from the Pseudozyma genus.

PMID- 17225102
TI  - Fermentative production of lactic acid from biomass: an overview on process
      developments and future perspectives.
AB  - The concept of utilizing excess biomass or wastes from agricultural and agro
      industrial residues to produce energy, feeds or foods, and other useful products
      is not necessarily new. Recently, fermentation of biomass has gained considerable
      attention due to the forthcoming scarcity of fossil fuels and also due to the
      necessity of increasing world food and feed supplies. A cost-effective viable
      process for lactic acid production has to be developed for which several attempts
      have been initiated. Fermentation techniques result in the production of either
      D: (-) or L: (+) lactic acid, or a racemic mixture of both, depending on the type
      of organism used. The interest in the fermentative production of lactic acid has
      increased due to the prospects of environmental friendliness and of using
      renewable resources instead of petrochemicals. Amylolytic bacteria Lactobacillus
      amylovorus ATCC 33622 is reported to have the efficiency of full conversion of
      liquefied cornstarch to lactic acid with a productivity of 20 g l(-1) h(-1). A
      maximum of 35 g l(-1) h(-1) was reported using a high cell density of L.
      helveticus (27 g l(-1)) with a complete conversion of 55- to 60-g l(-1) lactose
      present in whey. Simultaneous saccharification and fermentation is proved to be
      best in the sense of high substrate concentration in lower reactor volume and low
      fermentation cost. In this review, a survey has been made to see how effectively
      the fermentation technology explored and exploited the cheaply available source
      materials for value addition with special emphasis on lactic acid production.

PMID- 17225103
TI  - Exploitation of Dunaliella for beta-carotene production.
AB  - Halotolerant microalga Dunaliella, which is exploited for the production of dried
      biomass or cell extract, is used as a medicinal food. With the advancement in
      this field in recent years, the production of bio-organic compounds such as beta
      carotene is established in many countries. Large-scale production of beta
      carotene is controlled by numerous stress factors like high light intensity, high
      salinity, temperature and availability of nutrients. The state-of-the-art
      strategies in industries in closed systems under new set of inductive factors
      will additionally promote the ease of commercial production of beta-carotene.
      This review mainly focuses on the different methodologies employed recently for
      the optimum production of beta-carotene from Dunaliella species.

PMID- 17225104
TI  - Transcriptional analysis of L-methionine catabolism in Brevibacterium linens
      ATCC9175.
AB  - The expression of genes possibly involved in L-methionine and lactate catabolic
      pathways were performed in Brevibacterium linens (ATCC9175) in the presence or
      absence of added L-methionine. The expression of 27 genes of 39 selected genes
      differed significantly in L-methionine-enriched cultures. The expression of the
      gene encoding L-methionine gamma-lyase (MGL) is high in L-methionine-enriched
      cultures and is accompanied by a dramatic increase in volatile sulfur compounds
      (VSC) biosynthesis. Several genes encoding alpha-ketoacid dehydrogenase and one
      gene encoding an acetolactate synthase were also up-regulated by L-methionine,
      and are probably involved in the catabolism of alpha-ketobutyrate, the primary
      degradation product of L-methionine to methanethiol. Gene expression profiles
      together with biochemical data were used to propose catabolic pathways for L
      methionine in B. linens and their possible regulation by L-methionine.

PMID- 17225105
TI  - Mechanism of calcium accumulation in acetate-fed aerobic granule.
AB  - High calcium content has been widely reported in acetate-fed aerobic granules,
      but the reason behind this is unclear yet. By SEM-energy dispersive X-ray mapping
      analysis, this study showed that the majority of calcium was presented in the
      central part of the acetate-fed aerobic granule, and the granule shell part was
      nearly calcium-free. The elemental analysis of calcium ions coupled with the
      chemical titration of carbonate further revealed that the calcium ions that
      accumulated in the acetate-fed aerobic granule mainly existed in the form of
      calcium carbonate (CaCO3). The formation of the CaCO3 appeared to be highly
      dependent on the size of the aerobic granule, i.e., the CaCO3 precipitation was
      found only in aerobic granules with radiuses larger than 0.5 mm. These
      experimental observations with regard to the formation of CaCO3 in the acetate
      fed aerobic granule were further confirmed by the model simulation, which was
      based on the principles of mass diffusion and carbonate dissociation in liquid
      phase. This study for the first time showed that the size of the acetate-fed
      aerobic granule would indeed play an essential role in the CaCO3 formation, and
      provided experimental evidence that a crystal CaCO3 core was not necessarily
      required for granulation.

PMID- 17225106
TI  - ICP-MS as a novel detection system for quantitative element-tagged immunoassay of
      hidden peanut allergens in foods.
AB  - A novel ICP-MS-based ELISA immunoassay via element-tagged determination was
      devised for quantitative analysis of hidden allergens in food. The method was
      able to detect low amounts of peanuts (down to approximately 2 mg peanuts kg(-1)
      cereal-based matrix) by using a europium-tagged antibody. Selectivity was proved
      by the lack of detectable cross-reaction with a number of protein-rich raw
      materials.

PMID- 17225107
TI  - Determination of ethylphenols in wine by in situ derivatisation and headspace
      solid-phase microextraction-gas chromatography-mass spectrometry.
AB  - Contamination by Brettanomyces is a frequent problem in many wineries that has a
      dramatic effect on wine aroma and hence its quality. The yeast
      Brettanomyces/Dekkera is involved in the formation of three important volatile
      ethylphenols-4-ethylphenol, 4-ethylguaiacol and 4-ethylcatechol-that transmit an
      unpleasant aroma to wine that has often been described as 'medicinal', 'stable'
      or 'leather'. This study proposes an in situ derivatisation and headspace solid
      phase microextraction- gas chromatography coupled to mass spectrometry method to
      determine the three ethylphenols in red Brettanomyces-tainted wines. The most
      important variables involved in the derivatisation (acetic anhydride and base
      concentration) and the extraction (extraction temperature and salt addition)
      processes were optimised by experimental design. The optimal conditions using 4
      mL of wine in 20-mL sealed vials were 35 muL of acetic anhydride per millilitre
      of wine, 1 mL of 5.5% potassium carbonate solution and 0.9 g of sodium chloride
      and the extraction was performed with a divinylbenzene-carboxen
      poly(dimethylsiloxane) fibre at 70 degrees C for 70 min. Then, the performance
      characteristics were established using wine samples spiked with the ethylphenols.
      For all compounds, the detection limits were below the odour threshold reported
      in the literature and they were between 2 and 17 microg L(-1) for 4-ethylguaiacol
      and 4-ethylphenol, respectively. Intermediate precision (as relative standard
      deviation) was acceptable, with values ranging from 0.3 to 12.1%. Finally, the
      method was applied in the analysis of aged Brettanomyces-tainted wines.

PMID- 17225108
TI  - Analytical methods for the determination of selected steroid sex hormones and
      corticosteriods in wastewater.
AB  - An analytical method for the determination of 12 selected estrogens, progestagens
      and corticosteroids is presented. The optimization of the method, including
      liquid chromatography separation, extraction on a solid phase, purification on a
      silica gel cartridge and detection by mass spectrometry, is described. Both the
      repeatability, with relative standard deviation ranging from 1.4 to 2.7%, and the
      accuracy, with recoveries ranging from 92.7 to 102.4%, were very satisfactory for
      ten of the target analytes. The limits of detection were lower than 1 ng/L for
      progestagens, androgens and corticosteroids, and ranged between 0.9 and 4.3 ng/L
      for estrogens. The results of the analysis of two sewage treatment plants in the
      area of Lyon (France) by this method reveal that all the compounds investigated
      are present in the effluents. The estrogen most frequently detected was estrone,
      with a median of 26.1 ng/L. The target progestagens were detected with
      concentrations ranging between 5 and 41 ng/L. Androgens were also present in most
      of the samples in the range 1-30 ng/L, while the corticosteroids were present
      only in one plant, with a median of 31.9 ng/L.

PMID- 17225109
TI  - New sample treatment for determination of linear alkylbenzene sulfonate (LAS) in
      agricultural soils by liquid chromatography with fluorescence detection.
AB  - A new sample-treatment procedure has been developed for determination of total
      linear alkylbenzene sulfonate (LAS), i.e. homologues and isomers, in agricultural
      soil. The procedure involves two steps, ultrasound-assisted extraction of LAS
      from the samples with methanol then clean-up of the methanolic extracts and
      preconcentration of the LAS by solid-phase extraction on two adsorbent cartridges
      (SAX and C18). The ultrasound-assisted procedure reduces extraction time (10 min
      in contrast with 6-12 h for conventional Soxhlet extraction) and requires only
      small volumes of organic solvent. The effect of different variables interacting
      in the ultrasound-assisted extraction process was studied. Finally, separation
      and quantification of the homologues and isomers of LAS was performed by liquid
      chromatography with fluorescence detection (LC-FD). 2-Octylbenzenesulfonic acid
      sodium salt (Na-2OC8-LAS) was used as internal standard. The proposed method was
      satisfactorily used for determination of LAS in agricultural soil samples from
      the fertile plain of Granada (Spain).

PMID- 17225110
TI  - A microscale device for measuring emissions from materials for indoor use.
AB  - Emission test chambers or cells are used to determine organic vapour emissions
      from construction products under controlled conditions. Polymeric car trim
      component emissions are typically evaluated using direct thermal
      desorption/extraction. The Microchamber/Thermal Extractor (mu-CTE, Markes
      International) was developed to provide both a complementary tool for rapid
      screening of volatile organic compound (VOC) emissions--suitable for industrial
      quality control--and a means for thermal extraction of larger, more
      representative samples of car trim components. To determine the degree of
      correlation between conventional emission test methods and the microchamber,
      experiments were carried out under different conditions of temperature, air
      change rate and sample conditioning time. Good quantitative and qualitative
      correlation was obtained for measurements at ambient temperature. Moreover, it
      was shown that ambient-temperature emissions data collected using the mu-CTE as
      rapidly as possible--i.e. with minimal or no sample conditioning time-
      nevertheless provided a reliable guide as to how well that material would perform
      in subsequent 3-day chamber tests of VOC emissions. The parameters found to have
      the greatest influence on data correlation for experiments carried out at
      elevated temperatures were the sample mass (for bulk emissions testing) and the
      conditioning time. The results also showed that, within the constraints of
      inherent sample homogeneity, the mu-CTE gave reproducible emissions data, despite
      its small sample size/capacity relative to that of conventional chambers.
      Preliminary results of modelling the air flow within a microchamber using
      computational fluid dynamics showed a high degree of turbulent flow and two
      potential areas of still air which could cause sink effects. However, the
      experimental data reported here and in previous studies showed enhanced recovery
      of semivolatile components from the mu-CTE relative to a recovery from a 1 m(3)
      conventional chamber. This indicates that if these areas of relatively still air
      are present within the microchamber, they do not appear to be significant in
      practice.

PMID- 17225112
TI  - Extending the dynamic range of electrochemical sensors using multiple modified
      electrodes.
AB  - Multiple electrodes, combined with a chemometric strategy to calibrate the
      measurement response, have been used for the determination of an analyte across a
      broader dynamic range than is possible with a single electrode. The model system
      used for the detection of copper comprised electrodes modified with a self
      assembled monolayer. The electrodes were modified with the copper-complexing
      species (3-mercaptopropionic acid, thioctic acid, and the peptides cysteine and
      Gly-Gly-His) and copper was determined over concentrations ranging from nanomolar
      to millimolar using voltammetric analysis. We have demonstrated that by combining
      the calibration functions from the four electrodes a better estimate (i.e. with
      smaller variance) of the concentration of the analyte is obtained. Measurement
      uncertainty is expressed for independently prepared electrodes, which allows the
      possibility of commercial production and factory calibration. The principles of
      using multiple electrodes modified with recognition elements with different
      affinities for the target analyte to extend the dynamic range of sensors is a
      general one that could be applied to other analytes.

PMID- 17225111
TI  - Monitoring the effect of chemicals on biological communities. The biofilm as an
      interface.
AB  - Biofilms can be regarded as early warning systems for detection of the effects of
      toxicants on aquatic systems, because they have been successfully used for
      detection of other environmental stressors (e.g. pH, salinity, organic
      pollution). A variety of methods is used for detection of the effects of
      toxicants by use of biofilms. The methods range from structurally-based to
      functionally-based, and from in vitro-based to systemic approaches. Physiological
      approaches may be appropriate for detection of acute effects. Among these
      methods, photosynthesis is more related to the effect of toxicants affecting
      algal communities, directly or indirectly, and extracellular enzyme activity is
      less specific. Selecting one or the other may depend on the suspected direct
      effect of the toxicant. Integrated studies have revealed the relevance of
      toxicants to top-down or bottom-up regulation of the biofilm community.
      Persistent or chronic effects should affect other biofilm indicators, for example
      growth or biomass-related factors (e.g. chlorophyll), or community composition.
      Among these, community composition might better reflect the effects of the
      toxicant(s), because this may cause a shift from a sensitive to a progressively
      tolerant community. Community composition-based approaches do not usually
      adequately reflect cause-effect relationships and require complementary analysis
      of properties affected in the short-term, for example physiological properties.
      The current array of methods available must be wisely combined to disentangle the
      effects of chemicals on biofilms, and whether these effects are transient or
      persistent, to successfully translate the chemical action of toxicants into the
      effect they might have on the river ecosystem.

PMID- 17225113
TI  - Early hospital discharge with oral antimicrobial therapy in patients with
      hematologic malignancies and low-risk febrile neutropenia.
AB  - Although consensus exists relating criteria for the identification of low-risk
      patients with febrile neutropenia, no clear indication on how to manage these
      patients has been so far provided particularly in outpatients affected by
      hematologic malignancies. The feasibility and safety of early discharge was
      prospectively evaluated in 100 outpatients with hematologic malignancies and
      febrile neutropenia. A strategy considering the risk-index of the Multinational
      Association of Supportive Care in Cancer (MASCC) was applied. High-risk patients
      were entirely managed at hospital. Low-risk patients were early discharged if
      they were afebrile since 48 h and not on supportive therapy requiring
      hospitalization. Out of 90 low-risk episodes, in 69 instances (76.7%), patients
      were discharged after a median of 4 days and continued home therapy with oral
      cefixime (78%) or other antibiotics. Only five outpatients (7.2%) had fever
      recurrence. Twenty-one low-risk patients were not early discharged due to
      worsening conditions (three deaths), need of multiple daily dose therapy, or
      discharge refuse. No clinical characteristic was able to predict the eligibility
      for early discharge. The MASCC risk-index is a useful aid in the identification
      of high-risk febrile neutropenia needing whole in-hospital treatment. As for low
      risk patients, hospitalization at least in the first days of fever is required.
      Cefixime could be included among the oral antibacterial drugs to be used in the
      outpatient treatment of adult patients with febrile neutropenia.

PMID- 17225114
TI  - Tumour thrombus in the superior vena cava from anaplastic carcinoma of the
      thyroid: FDG-PET/CT imaging findings.

PMID- 17225115
TI  - Is radionuclide transmission scanning obsolete for dual-modality PET/CT systems?

PMID- 17225116
TI  - Role of 99mTc-sestamibi SPECT in accurate selection of primary hyperparathyroid
      patients for minimally invasive radio-guided surgery.

PMID- 17225118
TI  - Reduction of FDG uptake in brown adipose tissue in clinical patients by a single
      dose of propranolol.
AB  - PURPOSE: Uptake in brown adipose tissue (hibernating fat) is sometimes seen at
      FDG-PET examinations. Despite a characteristic appearance, this may hide
      clinically relevant uptake. Stimulation of the sympathetic nervous system
      increases glucose uptake of brown fat. We now re-examine patients with brown fat
      activity that could disguise tumour uptake after pre-treatment with propranolol
      (a non-selective beta-blocker) in order to reduce the uptake. Our first
      examinations of this kind are reported. METHODS: Eleven patients with strong
      brown fat uptake were studied. There was a mean of 5 days (range 2-8) between the
      examinations. At the second examination, 80 mg of propranolol was given orally 2
      h before FDG administration. In addition to visual evaluation of the brown fat
      uptake, SUV assessments of the uptake in brown fat, lung, heart, liver, spleen
      and bone marrow were made. RESULTS: All patients showed complete or almost
      complete disappearance of the brown fat activity at the second examination (p <
      0.001) both upon visual evaluation and when comparing SUVs. In seven patients
      there was also uptake in a known or strongly suspected malignancy, which remained
      unchanged between the examinations. Beyond an insignificant decrease in the
      myocardial uptake, there was no redistribution to the various examined organs at
      the second examination. CONCLUSION: Pre-treatment with a single dose of
      propranolol blocks the FDG uptake in brown adipose tissue, thereby increasing the
      specificity of the examination. The tumour uptake seems not to be impaired.

PMID- 17225120
TI  - Unilateral arytenoid adduction improves voice in a patient with bilateral vocal
      fold immobility.
AB  - Bilateral vocal fold immobility (BVFI) due to prolonged endotracheal intubation
      resulted in aphonia without any airway morbidity and was treated by several
      reconstructive procedures. Laryngeal reinnervation and silicone implantation
      failed to medialize one of those two fixed cords. Arytenoid adduction (AA)
      eventually achieved this goal. To select an optimal reconstructive procedure, a
      careful perusal of the history and head and neck examination including laryngeal
      electromyography, are necessary to determine the causes. AA procedure played an
      essential clinical indication in this study, not just an adjunct to the
      medialization laryngoplasty as usual. Since both the vocal cords positions were
      ranked as lateral positions subjectively, the full adduction for one of those two
      fixed vocal cords was performed without significant airway obstruction. The
      practice in this study provided an experience in correcting the voice in patients
      with BVFI. We need further experience to medialize the vocal cord in an
      appropriate magnitude since its counterpart may position variously and compromise
      the airway.

PMID- 17225119
TI  - Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to
      those labelled with other radiometals?
AB  - PURPOSE: Gallium-68 is a metallic positron emitter with a half-life of 68 min
      that is ideal for the in vivo use of small molecules, such as [68Ga
      DOTA,Tyr3]octreotide, in the diagnostic imaging of somatostatin receptor-positive
      tumours. In preclinical studies it has shown a striking superiority over its
      111In-labelled congener. The purpose of this study was to evaluate whether third
      generation somatostatin-based, radiogallium-labelled peptides show the same
      superiority. METHODS: Peptides were synthesised on solid phase. The receptor
      affinity was determined by in vitro receptor autoradiography. The internalisation
      rate was studied in AR4-2J and hsst-HEK-transfected cell lines. The
      pharmacokinetics was studied in a rat xenograft tumour model, AR4-2J. RESULTS:
      All peptides showed high affinities on hsst2, with the highest affinity for the
      Ga(III)-complexed peptides. On hsst3 the situation was reversed, with a trend
      towards lower affinity of the Ga(III) peptides. A significantly increased
      internalisation rate was found in sst2-expressing cells for all 67Ga-labelled
      peptides. Internalisation into HEK-sst3 was usually faster for the 111In-labelled
      peptides. No internalisation was found into sst5. Biodistribution studies
      employing [67Ga-DOTA,1-Nal3]octreotide in comparison to [111In-DOTA,1
      Nal3]octreotide and [67Ga-DOTA,Tyr3]octreotide showed a significantly higher and
      receptor-mediated uptake of the two 67Ga-labelled peptides in the tumour and
      somatostatin receptor-positive tissues. A patient study illustrated the potential
      advantage of a broad receptor subtype profile radiopeptide over a high-affinity
      sst2-selective radiopeptide. CONCLUSION: This study demonstrates that 67/68Ga
      DOTA-octapeptides show distinctly better preclinical, pharmacological
      performances than the 111In-labelled peptides, especially on sst2-expressing
      cells and the corresponding animal models. They may be excellent candidates for
      further development for clinical studies.

PMID- 17225121
TI  - Predictive impact of elevated serum level of IL-18 for early renal dysfunction in
      type 2 diabetes: an observational follow-up study.
AB  - AIMS/HYPOTHESIS: The early identification of type 2 diabetic patients at risk of
      developing microalbuminuria-an independent risk factor for renal and
      cardiovascular diseases-is important to improve the patients' outcomes. We
      investigated whether serum levels of IL-18, a proinflammatory cytokine, were a
      predictor of early renal dysfunction. MATERIALS AND METHODS: A total of 249
      Japanese type 2 diabetic patients without overt proteinuria were enrolled in an
      observational follow-up study (median follow-up 7 years), and their stage of
      diabetic nephropathy was classified and their estimated glomerular filtration
      rate (eGFR) was calculated annually. RESULTS: At baseline, serum levels of IL-18
      were higher in subjects with microalbuminuria (n = 76) than in those with
      normoalbuminuria (n = 173). Elevated serum levels of IL-18 were associated with
      the progression of nephropathy to a higher stage in normoalbuminuric subjects
      (118 [interquartile range 91-159] ng/l vs 155 [interquartile range 121-205] ng/l,
      p = 0.003), but not in microalbuminuric subjects (154 [interquartile range 113
      200] ng/l vs 160 [interquartile range 101-190] ng/l, p = 0.50). The adjusted risk
      for developing microalbuminuria was 3.6 (95% CI 1.2-10.4) in normoalbuminuric
      subjects with serum IL-18 levels above the median (>/=134.6 ng/l), and was
      significantly enhanced in those urinary AERs at the upper end of the normal range
      (7.5 mug/min </= AER < 20 microg/min). Furthermore, the annual rate of decline in
      eGFR, when examined in the study population as a whole, was significantly greater
      in subjects with serum IL-18 levels above the median than in other subjects.
      CONCLUSIONS/INTERPRETATION: The results of our observational follow-up study
      indicate that elevated serum levels of IL-18 may be a predictor of future renal
      dysfunction in type 2 diabetic patients with normoalbuminuria.

PMID- 17225122
TI  - Increasing prevalence of type 2 diabetes in a Scottish population: effect of
      increasing incidence or decreasing mortality?
AB  - AIMS/HYPOTHESIS: We examined incidence, prevalence and mortality from type 2
      diabetes mellitus in a Scottish population over 12 years, and evaluated the
      effects on prevalence of increasing incidence and decreasing mortality. MATERIALS
      AND METHODS: We used a diabetes clinical information system in Tayside
      (population 387,908), Scotland, to identify new cases of type 2 diabetes between
      1993 and 2004 and to calculate incidence rates and mid-year prevalence. We
      defined mortality rates as the number of deaths of diabetic people divided by mid
      year prevalence. We used logistic and Poisson regression to analyse trends. We
      then modelled the increase in prevalence for each year for three scenarios, based
      on whether mortality or incidence rates remained unchanged from 1993. RESULTS:
      There was a doubling in incidence and prevalence of type 2 diabetes in Tayside
      over the 12 years, with statistically significant increasing trends of 6.3 and
      6.7% per year respectively. The mortality rate decreased. If incidence and
      mortality had remained at 1993 levels, there would have been an increase in
      prevalence of 855 per 100,000 in 2003, accounting for 60.1% of the actual
      increase of 1,423 per 100,000. If there had been no mortality decrease,
      prevalence in 2003 would have been very similar to the actual prevalence
      observed. CONCLUSIONS/INTERPRETATION: Decreasing mortality rates in Tayside had
      less effect on the increase in prevalence than did increasing incidence. Even if
      incidence and mortality remain unchanged, prevalence will increase by over 20% in
      the next decade.

PMID- 17225123
TI  - C-peptide: a redundant relative of insulin?

PMID- 17225124
TI  - Inappropriate suppression of glucagon during OGTT but not during isoglycaemic
      i.v. glucose infusion contributes to the reduced incretin effect in type 2
      diabetes mellitus.
AB  - AIMS/HYPOTHESIS: We investigated glucagon responses during OGTT and isoglycaemic
      i.v. glucose infusion, respectively, to further elucidate the mechanisms behind
      the glucose intolerance in patients with type 2 diabetes. MATERIALS AND METHODS:
      Ten patients (eight men) with type 2 diabetes (age: 64 [51-80] years; BMI: 23 [21
      26] kg/m(2); HbA(1c): 6.9 [6.2-8.7]%, values mean [range]) and ten control
      subjects matched for sex, age and BMI were studied. Blood was sampled on two
      separate days following a 4-h 50-g OGTT and an isoglycaemic i.v. glucose
      infusion, respectively. RESULTS: Isoglycaemia during the 2 days was obtained in
      both groups. In the control subjects no difference in glucagon suppression during
      the first 45 min of OGTT and isoglycaemic i.v. glucose infusion (-36 +/- 12 vs 
      64 +/- 23 mmol/l x 45 min; p = NS) was observed, whereas in the group of patients
      with type 2 diabetes significant glucagon suppression only occurred following
      isoglycaemic i.v. glucose infusion (-63 +/- 21 vs 10 +/- 16 mmol/l x 45 min; p =
      0.002). The incretin effect was significantly reduced in patients with type 2
      diabetes compared with control subjects, but no significant differences in the
      secretion of glucagon-like peptide-1 or glucose-dependent insulinotropic
      polypeptide between the two groups during OGTT or isoglycaemic i.v. glucose
      infusion, respectively, could explain this. CONCLUSIONS/INTERPRETATION:
      Attenuated and delayed glucagon suppression in patients with type 2 diabetes
      occurs after oral ingestion of glucose, while isoglycaemic i.v. administration of
      glucose results in normal suppression of glucagon. We suggest that this
      phenomenon contributes both to the glucose intolerance and to the reduced
      incretin effect observed in patients with type 2 diabetes.

PMID- 17225126
TI  - Endoscopic controlled intramedullary fracture reduction. A case report about
      closed fracture reduction under visual control.
AB  - Intramedullary bone endoscopy (IBE) was introduced as a new endoscopic technique
      in the year 2002 to achieve and manipulate the medullary canal of long bone under
      direct visual control. We report on a patient with a proximal femur fracture,
      where the new technique of IBE was used for intramedullary fracture reduction
      under visual control for the first time. Thus, the intraoperative use of an image
      intensifier was reduced.

PMID- 17225125
TI  - Activation of c-Jun NH2-terminal kinase (JNK) pathway during islet
      transplantation and prevention of islet graft loss by intraportal injection of
      JNK inhibitor.
AB  - AIMS/HYPOTHESIS: Although application of the Edmonton protocol has markedly
      improved the outcome for pancreatic islet transplantation, the insulin
      independence rate after islet transplantation from one donor pancreas has
      remained low. During the isolation process and subsequent clinical
      transplantation, islets are subjected to severe adverse conditions that impair
      survival and ultimately contribute to graft failure. The aim of this study was to
      map the c-Jun NH2-terminal kinase (JNK) pathway that mediates islet loss during
      islet transplantation and to clarify whether intraportal injection with JNK
      inhibitor during islet transplantation can prevent islet graft loss. METHODS: We
      measured JNK activity in the liver, fat and muscle of diabetic mice and in the
      liver immediately after islet transplantation. We examined the effect of
      intraportal injection of JNK inhibitory peptide at islet transplantation.
      RESULTS: JNK activity became progressively higher at least until 24 h after
      transplantation. The cell-permeable peptide of JNK inhibitor was delivered not
      only in the liver but also in other insulin target organs, preventing JNK
      activation in the liver at least until 24 h after transplantation and reducing
      JNK activity in these insulin target organs. Moreover, the peptide inhibitor
      prevented islet graft loss immediately after transplantation and improved islet
      transplant outcome. CONCLUSIONS/INTERPRETATION: These findings suggest that
      control of the JNK pathway is extremely important in islet transplantation and
      that intraportal injection of JNK inhibitor during islet transplantation
      (addition of JNK inhibitor to transplant media) could prevent the impairment of
      islet cells, leading to improved outcome for pancreatic islet transplantation.

PMID- 17225127
TI  - Long-term absenteeism due to sickness in Sweden. How long does it take and what
      happens after?
AB  - In this paper, we analyze exits from long-term sickness spells in Sweden. Using
      data for more than 2,500 people, the aim is to analyze the transition to
      different states: return to work, full disability pension, partial disability
      pension, and other exits from the labor force. Given the complexity of the exit
      decision, which encompasses both the individual's choice, the medical evaluation
      and the decision of the insurance adjudicator, we consider the outcome as being
      the result of two aspects of the exit process: one that governs the duration of a
      spell prior to the decision to exit, and another that governs the type of exit.
      Therefore, the analysis is done in two steps: first, we analyze the duration of
      the sickness spells, and then we analyze the process that governs the type of
      exit. The results indicate that both individual characteristics and push factors,
      such as regional unemployment, are important for both components of the decision
      process.

PMID- 17225128
TI  - Discussion point: should governments buy drug patents?
AB  - Between just 1995 and 2003, the number of new chemical entities fell from 45 to
      25, while the costs increased by two and a half times in the same period. Firms
      in the USA accounted for more than half of biotech drugs from 1982 to 2003.
      European firms are losing competitiveness. In this hostile environment for
      investment in pharmaceutical R&D, providing quick access to market for real
      innovations is the main challenge for regulatory agencies. More initiatives, more
      entrepreneurial spirit and easier work regulation are needed to facilitate the
      growth of firms in this field, especially in emerging economies like the Spanish.
      A new open source model proposes the use of pre-competitive public platforms
      formed by young and qualified human capital carrying out research in areas not
      sufficiently attractive for private initiatives, followed by the introduction of
      pharmaceutical companies to carry out the clinical research. The last step would
      be fast and effective approval by assessment agencies. Governments should,
      therefore, facilitate the regulation of socially effective innovations, bringing
      in manufacturers to take part in the post-clinical trial period after entering
      the market. The gathering of incentives between regulatory agencies and
      pharmaceutical industry must be approached through innovation and authorization
      stimulating systems.

PMID- 17225130
TI  - Stochastic simulation of daily air temperature and precipitation from monthly
      normals in North America north of Mexico.
AB  - A simple, stochastic daily temperature and precipitation generator (TEMPGEN) was
      developed to generate inputs for the study of the effects of climate change on
      models driven by daily weather information when climate data are available as
      monthly summaries. The model uses as input only 11 sets of monthly normal
      statistics from individual weather stations. It needs no calibration, and was
      parameterized and validated for use in Canada and the continental United States.
      Monthly normals needed are: mean and standard deviation of daily minimum and
      maximum temperature, first and second order autoregressive terms for daily
      deviations of minimum and maximum temperatures from their daily means,
      correlation of deviations of daily minimum and maximum temperatures, total
      precipitation, and the interannual variance of total precipitation. The
      statistical properties and distributions of daily temperature and precipitation
      data produced by this generator compared quite favorably with observations from
      708 stations throughout North America (north of Mexico). The algorithm generates
      realistic seasonal patterns, variability and extremes of temperature,
      precipitation, frost-free periods and hot spells. However, it predicts less
      accurately the daily probability of precipitation, extreme precipitation events
      and the duration of extreme droughts.

PMID- 17225129
TI  - Cost-effectiveness of extended prophylaxis with fondaparinux compared with low
      molecular weight heparin against venous thromboembolism in patients undergoing
      hip fracture surgery.
AB  - A model was developed to estimate costs and clinical effectiveness of
      fondaparinux compared with enoxaparin after hip fracture surgery in Sweden.
      Outcomes and costs of venous thromboembolism (VTE)-related care from a health
      care perspective were incorporated, with symptomatic deep-vein thrombosis and
      pulmonary embolism, recurrent VTE, post-thrombotic syndrome, major haemorrhage
      and all-cause death being included. Event probabilities were derived from
      fondaparinux clinical trial data and published data. VTE-related resource use and
      associated costs as well as costs of prophylaxis were based on local Swedish
      data. Extended prophylaxis with fondaparinux could avoid an additional 28
      symptomatic VTE per 1,000 patients compared with extended prophylaxis with
      enoxaparin in hip fracture surgery patients. Although the prophylaxis costs were
      higher in the fondaparinux group, these were offset by the lower costs associated
      with treating fewer VTE, which thus indicates that extended fondaparinux
      prophylaxis is the dominant alternative when compared with enoxaparin in hip
      fracture surgery.

PMID- 17225131
TI  - Value of MR phase-contrast flow measurements for functional assessment of
      pulmonary arterial hypertension.
AB  - Goals of our study were to compare the pulmonary hemodynamics between healthy
      volunteers and patients with pulmonary arterial hypertension (PAH) and correlate
      MR flow measurements with echocardiography. Twenty-five patients with PAH and 25
      volunteers were examined at 1.5 T. Phase-contrast flow measurements were
      performed in the ascending aorta and pulmonary trunk, resulting in the following
      parameters: peak velocity (cm/s), average blood flow (l/min), time to peak
      velocity (ms), velocity rise gradient and pulmonary distensibility (cm(2)). The
      bronchosystemic shunt was calculated. In PAH patients transthoracic
      echocardiography and right-heart catheterization (RHC) served as the gold
      standard. In comparison to volunteers, the PAH patients showed significantly
      reduced pulmonary velocities (P = 0.002), blood flow (P = 0.002) and pulmonary
      distensibility (P = 0.008). In patients, the time to peak velocity was shorter
      (P<0.001), and the velocity rise gradient was steeper (P = 0.002) than in
      volunteers. While in volunteers the peak velocity in the aorta was reached
      earlier, it was the reverse in patients. Patients showed a significant
      bronchosystemic shunt (P = 0.01). No meaningful correlation was found between MRI
      measurements and echocardiography or RHC. MRI is a feasible technique for the
      differentiation between PAH and volunteers. Further studies have to be conducted
      for the absolute calculation of pressure estimates.

PMID- 17225132
TI  - Intramuscular cavernous hemangioma arising from masseter muscle: a diagnostic
      dilemma (2006: 12b).
AB  - We report here a case of intramuscular cavernous hemangioma of the right masseter
      muscle in a 41-year-old woman-misdiagnosed preoperatively as parotid tumor-along
      with its imaging and pathologic findings. Preoperative diagnosis of intramuscular
      cavernous hemangiomas of the masseter muscle is problematic, in that they may be
      confused with parotid tumor or other muscular lesions. In a patient with soft
      tissue mass suspected of representing a hemangioma, MR imaging may provide more
      specific information regarding the characteristics, the origin, and the extent of
      the lesion than other imaging modalities.

PMID- 17225133
TI  - [Introduction to the topic: local anaesthesia and Pandora's box].

PMID- 17225135
TI  - Autosomal recessive juvenile onset cataract associated with mutation in BFSP1.
AB  - A genome wide scan in a consanguineous family of Indian origin with autosomal
      recessive developmental cataracts was performed by two-point linkage analysis
      with 382 microsatellite markers. It showed linkage to markers on chromosome 20q,
      between D20S852 and D20S912, with a maximum lod score of 5.4 obtained with
      D20S860. This region encompasses the beaded filament structural protein 1 (BFSP1)
      gene. Direct sequencing revealed a 3343 bp deletion including exon 6 (c.736
      1384_c.957-66 del) predicted to result in a shift of the open reading frame. This
      mutation was absent in 50 control individuals from south India. This is the first
      report of a mutation in the BFSP1 gene associated with human inherited cataracts.
      This further increases the genetic heterogeneity of inherited cataracts and
      provides clues as to the importance of BFSP1 in the cell biology of intermediate
      filaments and their role in the eye lens.

PMID- 17225134
TI  - Eleven new putative aminergic G-protein coupled receptors from Amphioxus
      (Branchiostoma floridae): identification, sequence analysis and phylogenetic
      relationship.
AB  - We have identified eleven novel aminergic-like G-protein coupled receptor (GPCRs)
      sequences (named AmphiAmR1-11) by searching the genomic trace sequence database
      for the amphioxus species, Branchiostoma floridae. They share many of the
      structural motifs that have been used to characterize vertebrate and invertebrate
      aminergic GPCRs. A preliminary classification of these receptors has been carried
      out using both BLAST and Hidden Markov Model analyses. The amphioxus genome
      appears to express a number of D1-like dopamine receptor sequences, including one
      related to insect dopamine receptors. It also expresses a number of receptors
      that resemble invertebrate octopamine/tyramine receptors and others that resemble
      vertebrate alpha-adrenergic receptors. Amphioxus also expresses receptors that
      resemble vertebrate histamine receptors. Several of the novel receptor sequences
      have been identified in amphioxus cDNA libraries from a number of tissues.

PMID- 17225136
TI  - The configuration of the Cu2+ binding region in full-length human prion protein.
AB  - The cellular prion protein (PrP(C)) is a Cu(2+) binding protein connected to the
      outer cell membrane. The molecular features of the Cu(2+) binding sites have been
      investigated and characterized by spectroscopic experiments on PrP(C)-derived
      peptides and the recombinant human full-length PrP(C )(hPrP-[23-231]). The hPrP
      [23-231] was loaded with (63)Cu under slightly acidic (pH 6.0) or neutral
      conditions. The PrP(C)/Cu(2+)-complexes were investigated by extended X-ray
      absorption fine structure (EXAFS), electron paramagnetic resonance (EPR), and
      electron nuclear double resonance (ENDOR). For comparison, peptides from the
      copper-binding octarepeat domain were investigated in different environments.
      Molecular mechanics computations were used to select sterically possible
      peptide/Cu(2+) structures. The simulated EPR, ENDOR, and EXAFS spectra of these
      structures were compared with our experimental data. For a stoichiometry of two
      octarepeats per copper the resulting model has a square planar four nitrogen
      Cu(2+) coordination. Two nitrogens belong to imidazole rings of histidine
      residues. Further ligands are two deprotonated backbone amide nitrogens of the
      adjacent glycine residues and an axial oxygen of a water molecule. Our complex
      model differs significantly from those previously obtained for shorter peptides.
      Sequence context, buffer conditions and stoichiometry of copper show marked
      influence on the configuration of copper binding to PrP(C).

PMID- 17225137
TI  - A molecular dynamics study of Cyclophilin A free and in complex with the Ala-Pro
      dipeptide.
AB  - Six different molecular dynamics simulations of Cyclophilin A, three with the
      protein free in water and three with the Ala-Pro dipeptide bound to the protein,
      have been performed, and analysed with respect to structure and hydration of the
      active site. The water structure in the binding pocket of the free Cyclophilin A
      was found to mimic the experimentally obtained binding cis conformation of the
      dipeptide. Cyclophilin A is a peptidyl-prolyl cis-trans isomerase (PPIase), but
      the mechanism of the cis/trans isomerization is not exactly clear. This study was
      performed to understand better the binding between dipeptide and Cyclophilin A,
      but also two previously proposed isomerization mechanisms are discussed.

PMID- 17225138
TI  - The glutathione antioxidant system is enhanced in growth hormone transgenic coho
      salmon (Oncorhynchus kisutch).
AB  - Insertion of a growth hormone (GH) transgene in coho salmon results in
      accelerated growth, and increased feeding and metabolic rates. Whether other
      physiological systems within the fish are adjusted to this accelerated growth has
      not been well explored. We examined the effects of a GH transgene and feeding
      level on the antioxidant glutathione and its associated enzymes in various
      tissues of coho salmon. When transgenic and control salmon were fed to satiation,
      transgenic fish had increased tissue glutathione, increased hepatic glutathione
      reductase activity, decreased hepatic activity of the glutathione synthesis
      enzyme gamma-glutamylcysteine synthetase, and increased intestinal activity of
      the glutathione catabolic enzyme gamma-glutamyltranspeptidase. However, these
      differences were mostly abolished by ration restriction and fasting, indicating
      that upregulation of the glutathione antioxidant system was due to accelerated
      growth, and not to intrinsic effects of the transgene. Increased food intake and
      ability to digest potential dietary glutathione, and not increased activity of
      glutathione synthesis enzymes, likely contributed to the higher levels of
      glutathione in transgenic fish. Components of the glutathione antioxidant system
      are likely upregulated to combat potentially higher reactive oxygen species
      production from increased metabolic rates in GH transgenic salmon.

PMID- 17225140
TI  - [Urinary tract infections in infants and children -- a consensus on diagnostic,
      therapy and prophylaxis].
AB  - Urinary tract infections (UTI) are among the most common bacterial infections in
      infants and children. The early diagnosis of a pyelonephritis and its rapid,
      calculated antibacterial therapy are decisive for the prognosis. Urogenital
      anomalies, renal damage and bladder dysfunction may influence the risk of
      recurrences of UTI and pyelonephritic scarring. Diagnostic strategies therefore
      should focus on their early recognition. Pediatricians, urologists and
      infectiologists are cooperating in diagnostic, therapy and prophylaxis of UTI.
      The aim of the interdisciplinary consensus presented was to work out a concept
      which may help to manage childhood UTI in daily practice.

PMID- 17225139
TI  - Adjusting energy expenditures to energy supply: food availability regulates
      torpor use and organ size in the Chilean mouse-opossum Thylamys elegans.
AB  - We studied how food abundance and consumption regulates torpor use and internal
      organ size in the Chilean mouse-opossum Thylamys elegans (Dielphidae), a small
      nocturnal marsupial, endemic in southern South America. We predicted that
      exposure to food rations at or above the minimum energy levels necessary for
      maintenance would not lead to any signs of torpor, while reducing food supply to
      energy levels below maintenance would lead to marked increases in frequency,
      duration and depth of torpor bouts. We also analyzed the relationship between
      food availability and internal organ mass. We predicted a positive relationship
      between food availability and internal organ size once the effect of body size is
      removed. Animals were randomly assigned to one of two groups and fed either 70,
      100 or 130% of their daily energy requirement (DER). We found a positive and
      significant correlation between %DER and body temperature, and also between %DER
      and minimum body temperature. In contrast, for torpor frequency, duration and
      depth, we found a significant negative correlation with %DER. Finally, we found a
      significant positive correlation between the %DER and small intestine and ceacum
      dry mass. We demonstrate that when food availability is limited, T. elegans has
      the capacity to reduce their maintenance cost by two different mechanisms, that
      is, increasing the use of torpor and reducing organ mass.

PMID- 17225141
TI  - Differential effects of urapidil and doxazosin on heart rate.
AB  - OBJECTIVE: Although alpha-blockers are effective in lowering blood pressure, they
      may increase heart rate, an unwanted effect that could negatively affect outcome.
      However, the alpha-blocker urapidil might not increase heart rate due to its
      additional effect on 5-HT1A receptors. Therefore, we compared the effects of
      urapidil on heart rate with those of another alpha-blocker, doxazosin. METHODS:
      We performed a randomised, double-blind, placebo-controlled, cross-over study in
      12 healthy males who received single oral doses of 60 mg urapidil, 4 mg doxazosin
      and placebo. Four hours following drug intake, heart rate and blood pressure were
      measured at rest and during exercise. RESULTS: Both doxazosin and urapidil
      decreased blood pressure to the same extent. Compared to placebo, resting heart
      rate was significantly increased by doxazosin (+25%, P < 0.05) but not by
      urapidil (+12%, n.s.). Resting heart rate with doxazosin was significantly higher
      than with urapidil (P < 0.05). Similarly, the rate pressure product (RPP) at rest
      was increased by doxazosin (+17%, P < 0.05) but not by urapidil (+6%, n.s.).
      CONCLUSIONS: We conclude that the increase in heart rate caused by urapidil is
      less pronounced than that with doxazosin, a property that might favour urapidil
      in the treatment of arterial hypertension. In addition, only doxazosin (but not
      urapidil) increased the RPP at rest, a finding that might be helpful to explain
      why this drug was never shown to improve outcome in the treatment of arterial
      hypertension.

PMID- 17225142
TI  - Association of IL-10 level and IL-10 promoter SNPs with specific antibodies in
      penicillin-allergic patients.
AB  - OBJECTIVE: Our aim was to investigate the hypothesis that the sera interleukin-10
      (IL-10) level and polymorphic nucleotides within the IL-10 gene promoters would
      link to specific IgE and IgG production and the expression of penicillin allergy.
      METHODS: One hundred and two patients and 86 healthy subjects were chosen for
      assay of serum IL-10 level by enzyme-linked immunosorbent assay (ELISA) and type 
      1082 G/A and -819 C/T alleles by sequence-specific primer polymerase chain
      reaction (SSP-PCR). Radioallergosorbent test (RAST) and ELISA were used to
      examine eight types of specific immunoglobulin-E (IgE) and IgG antibodies,
      respectively, which included four types of antibodies to major and minor
      antigenic determinants. RESULTS: Compared with control subjects and patients with
      negative-specific IgE, there were significantly lower levels of IL-10 in patients
      with positive-specific IgE (P < 0.05). Similarly, there were significantly lower
      levels of IL-10 in patients with positive-specific IgG compared with normal
      controls and allergic patients with negative-specific IgG (P < 0.05). The visible
      negative correlations existed between IL-10 and four types of specific IgE
      [benzylpenicilloyl (BPO), phenoxomethylpenicilloyl (PVO), benzylpenicillanyl
      (BPA), amoxicillanyl (AXA)], and patients with three or more positive-specific
      IgE had significantly lower IL-10 levels than normal controls (P < 0.01). There
      was a declining trend for IL-10 level in serum with the increase in types of
      positive-specific IgE. But there was no significant difference in serum IL-10
      level between the positive skin-test group and the allergic-history group.
      Compared with controls and patients with negative antibodies, a significantly
      decreased frequency of the -1082 G allele was present in patients with positive
      antibodies (P < 0.01). The allele T and TT genotype at -819 C/T position had
      lower frequency in the negative-specific IgG group than that in the positive
      group and controls (P < 0.01). CONCLUSIONS: Positive specific IgE and IgG are
      associated with decreased IL-10 level in allergic reaction to penicillins. The
      distributions of genotype and frequency of allele at the -1082 G/A position may
      be associated with the production of both specific IgE and IgG antibodies.

PMID- 17225143
TI  - Cerebral and cerebellar ADC values during a migraine attack.
AB  - INTRODUCTION: We investigated the diffusion-weighted MRI changes, apparent
      diffusion coefficient (ADC) values, and conventional MRI findings in specific
      brain areas during migraine attacks in patients with and without aura. METHODS:
      Included in the study were 22 patients (2 male, 20 female) aged between 17 and 49
      years who were diagnosed as having migraine according to the diagnostic criteria
      of the International Headache Society. Also included in the study were 18 age-
      and sex-matched healthy volunteers. Hyperintense lesions were evaluated in
      conventional MR images. Heavily diffusion-weighted images, ADC maps, and
      segmented ADC maps generated for regional ADC (rADC) measurements, were also
      studied. ADC values from specific brain areas were used with appropriate region
      of interests (ROI). RESULTS: Migraine with aura was diagnosed in 13 patients and
      migraine without aura was diagnosed in 9 patients. A total of 23 hyperintense
      lesions within the periventricular white matter and deep white matter were
      detected in five patients (21.8%). All of these hyperintense lesions were seen in
      migraine patients with aura. In only one patient did a hyperintense lesion show
      an increased diffusion pattern on diffusion-weighted images and ADC maps. One
      hyperintense lesion was detected in the control group (5.5%). There was no
      significant difference in ADC values between the migraine and control groups.
      CONCLUSION: T2-weighted hyperintense lesions were significantly more frequent in
      migraine patients especially in those with aura than in the control group. No
      diffusion alterations in diffusion-weighted images were detected in the infra-
      and supratentorial brain areas during migraine attacks in patients with and
      without aura.

PMID- 17225144
TI  - [Idiopathic normal-pressure hydrocephalus. Flow measurement of cerebrospinal
      fluid using phase contrast MRI and its diagnostics importance].
AB  - AIM: The measurement of CSF flow in the aqueduct has been a focus of interest
      since the development of MR imaging (MRI) techniques for this purpose in
      diagnosing idiopathic normal-pressure hydrocephalus (iNPH).The purpose of this
      prospective study was to determine the ability of this diagnostic tool to replace
      invasive methods in establishing the diagnosis of iNPH. PATIENTS AND METHODS:
      Between January 2003 and April 2005, 61 patients with the Hakim triad of clinical
      symptoms and dilated ventricular systems underwent the intrathecal infusion test,
      cerebrospinal tap test, and phase-contrast MRI to measure CSF flow rate in the
      aqueduct. Shunted patients were controlled 12 months postoperatively. Pre- and
      postoperative clinical symptoms were evaluated with the Kiefer score. Outcome was
      calculated according to the NPH recovery rate. RESULTS: According to these
      criteria the patients were classified into groups of 41 with iNPH and 20 with
      brain atrophy. Of the iNPH patients, 39 were shunted and two did not agree to
      surgery. The mean Kiefer score of the shunted patients was statistically
      significantly lower after surgery. The aqueductal CSF flow rate of these patients
      was statistically analyzed and showed that a flow rate of more than 24.5 ml/min
      is 95% specific to iNPH. CONCLUSIONS: Measurement of the CSF flow rate in the
      aqueduct using phase-contrast MRI is a highly specific preselective method for
      diagnosing iNPH.

PMID- 17225145
TI  - [Negative response bias and the validity of personality profiles in
      neuropsychiatric assessment].
AB  - Although symptom validity tests have become available to German test users during
      the last few years, there is very little research into measures of negative
      response bias in personality assessment. The present study investigates the
      effects of negative response bias as measured by the Word Memory Test (WMT) and
      the Structured Inventory of Malingered Symptomatology (SIMS) on self-report
      personality scales. A retrospective analysis was performed on data from 93
      patients who had undergone neuropsychiatric assessment in the context of
      independent medical examination. Complete data sets were available for the WMT,
      the SIMS, and the Freiburg Personality Inventory-Revised (FPI-R). Significant
      differences were found for a number of personality scales, depending on WMT and
      SIMS classification. The FPI-R validity scale (Openness) was linked to neither
      WMT nor SIMS, whereas the results in the latter two instruments showed a
      significant overlap of classification results (phi=0.44). A principal axis
      analysis yielded corresponding results. It is concluded that self-report
      personality measures may be considerably distorted by negative response bias. FPI
      R Openness scale scores do not allow any interpretation in terms of negative
      response bias. More effort should be directed in German-speaking countries
      towards the development and validation of appropriate validity scales.

PMID- 17225146
TI  - Identification of three Zwittermicin A biosynthesis-related genes from Bacillus
      thuringiensis subsp. kurstaki strain YBT-1520.
AB  - Zwittermicin A (ZwA) is a novel, broad-spectrum linear aminopolyol antibiotic
      produced by some Bacillus cereus and Bacillus thuringiensis. However, only part
      of its biosynthesis cluster has been identified and characterized from B. cereus
      UW85. To better understand the biosynthesis cluster of ZwA, a bacterial
      artificial chromosome (BAC) library of B. thuringiensis subsp. kurstaki strain
      YBT-1520, a ZwA-producing strain, was constructed. Two BAC clones, 1F8 and 5E2,
      were obtained by PCR, which overlap the known ZwA biosynthesis cluster of B.
      cereus UW85. This ZwA biosynthesis cluster is at least 38.6 kb and is located on
      the chromosome, instead of the plasmid. Partial DNA sequencing revealed both BAC
      clones carry three new ZwA biosynthesis-related genes, zwa6, zwa5A and zwa5B,
      which were found at the corresponding location of B. cereus UW85. Putative amino
      acid sequences of these genes shown that ZWA6 is homologous to a typical
      carbamoyltransferase from Streptomyces avermitilis, while ZWA5A and ZWA5B are
      homologs of cysteine synthetase and ornithine cyclodeaminase which jointly
      synthesize 2,3-diaminopropionate in the viomycin biosynthesis pathway,
      respectively. The identification of these three genes further supports the
      hypothesized ZwA biosynthesis pathway.

PMID- 17225148
TI  - Posterior horn lateral meniscal tears simulating meniscofemoral ligament
      attachment in the setting of ACL tear: MRI findings.
AB  - PURPOSE: We have noted apparent far lateral meniscal attachment of the
      meniscofemoral ligament (MFL) with an anterior cruciate ligament (ACL) tear. This
      study evaluates MFL attachment and association with posterior horn lateral
      meniscus (PHLM) tear. MATERIALS AND METHODS: Nine months of knee arthroscopy
      reports were reviewed to classify the PHLM and ACL as torn or normal. After
      excluding those with prior knee surgery, MR images were reviewed by two
      radiologists to determine the number of images lateral to PCL, which showed the
      ligaments of Humphrey and Wrisberg visible as structures separate from the PHLM.
      Any patient with abnormal PHLM surface signal not continuous with the MFL was
      excluded. MRI findings were compared with arthroscopy using Student's t test and
      Fisher's exact test. RESULTS: Of the 54 participants, 5 had PHLM tears and 49
      were normal. Twenty-one had ACL tears; all those with an PHLM tear had an ACL
      tear. The ligament of Humphrey inserted on average 0.9 consecutive images lateral
      to the PCL without an PHLM tear and 4.7 with an PHLM tear; the ligament of
      Wrisberg inserted on average 3.0 consecutive images without an PHLM tear and 4.5
      with an PHLM tear (slice thickness/gap = 3 mm/0.5 mm). There was a significant
      association between PHLM tear and number of images (p = 0.0028), and between ACL
      tear and this type of PHLM tear (p = 0.0064). CONCLUSION: Apparent far lateral
      meniscal extension of a meniscofemoral ligament (greater than or equal to four
      images lateral to the PCL) should be considered as a possible PHLM tear,
      especially in the setting of an ACL tear.

PMID- 17225147
TI  - Intramedullary spinal cord abscess complicating thoracic spondylodiscitis caused
      by Bacteroides fragilis.
AB  - Intramedullary spinal cord abscess associated with infectious spondylodiscitis is
      a rare entity. The case of a 66-year-old man with an intramedullary spinal cord
      abscess complicating thoracic spondylodiscitis is presented. The patient was
      unable to ambulate independently due to weakness of the legs. MR imaging showed
      findings suggestive of infectious spondylodiscitis at the T5-T6 level associated
      with epidural and intramedullary spinal cord abscesses. Biopsy of the
      intervertebral disc was performed and Bacteroides fragilis was isolated.
      Antibiotic therapy was instituted, and MR imaging of the thoracic spine was
      performed 6 weeks after the initiation of treatment, showing resolution of the
      epidural and intramedullary spinal cord abscesses.

PMID- 17225149
TI  - Arcuate ligament of the wrist: normal MR appearance and its relationship to
      palmar midcarpal instability: a cadaveric study.
AB  - OBJECTIVE: To describe the magnetic resonance (MR) imaging and gross anatomic
      appearance of the scaphocapitate (SC) ligament and triquetrohamocapitate (THC)
      ligament, which are the radial and ulnar limbs of the composite arcuate ligament,
      a critical volar midcarpal stabilizing ligament. DESIGN: T1 spin-echo and 3D
      gradient-echo MR imaging in the standard, coronal oblique, and axial oblique
      planes were performed both before and following midcarpal arthrography in seven
      cadaveric wrists. The seven specimens were then sectioned in selected planes to
      optimally visualize the SC and THC ligaments. These specimens were analyzed and
      correlated with their corresponding MR images. RESULTS: The SC and THC ligaments
      can be visualized in MR images as structures of low signal intensity that form an
      inverted "V" joining the proximal and distal carpal rows. The entire ligamentous
      complex is best visualized with coronal and axial oblique MR imaging but can also
      be seen in standard imaging planes. CONCLUSION: SC and THC ligaments together
      form the arcuate ligament of the wrist. Their function is crucial to the normal
      functioning of the wrist. Palmar midcarpal instability (PMCI) is a resulting
      condition when abnormalities of these ligaments occur. Dedicated MR imaging in
      the coronal and axial imaging planes can be performed in patients suspected of
      having PCMI.

PMID- 17225150
TI  - Magnetic resonance imaging findings associated with surgically proven rotator
      interval lesions.
AB  - OBJECTIVE: To identify shoulder magnetic resonance imaging (MRI) findings
      associated with surgically proven rotator interval abnormalities. MATERIALS AND
      METHODS: The preoperative MRI examinations of five patients with surgically
      proven rotator interval (RI) lesions requiring closure were retrospectively
      evaluated by three musculoskeletal-trained radiologists in consensus. We assessed
      the structures in the RI, including the coracohumeral ligament, superior
      glenohumeral ligament, fat tissue, biceps tendon, and capsule for variations in
      size and signal alteration. In addition, we noted associated findings of rotator
      cuff and labral pathology. RESULTS: Three of three of the MR arthrogram studies
      demonstrated extension of gadolinium to the cortex of the undersurface of the
      coracoid process compared with the control images, seen best on the sagittal
      oblique images. Four of five of the studies demonstrated subjective thickening of
      the coracohumeral ligament, and three of five of the studies demonstrated
      subjective thickening of the superior glenohumeral ligament. Five of five of the
      studies demonstrated a labral tear. CONCLUSIONS: The MRI arthrogram finding of
      gadolinium extending to the cortex of the undersurface of the coracoid process
      was noted on the studies of those patients with rotator interval lesions at
      surgery in this series. Noting this finding-especially in the presence of a
      labral tear and/or thickening of the coracohumeral ligament or superior
      glenohumeral ligament-may be helpful in the preoperative diagnosis of rotator
      interval lesions.

PMID- 17225151
TI  - Tenosynovial giant cell tumor and pigmented villonodular synovitis: a proposal
      for unification of these clinically distinct but histologically and genetically
      identical lesions.

PMID- 17225152
TI  - A subchondral fracture in transient osteoporosis of the hip.
AB  - Although subchondral changes are reported to be associated with transient
      osteoporosis of the hip (TOH), the etiology of this disorder is unknown.In this
      paper, we describe a 45-year-old man with TOH who underwent both MRI and CT
      examinations. Plain radiographs obtained 2 months after the onset of hip pain
      showed a focal loss of radiodensity in the left femoral head. MRI revealed a bone
      marrow edema pattern in the left femoral head and neck with an associated
      subchondral serpiginous low signal intensity line on the T1-weighted images. A CT
      scan showed a subchondral fracture in the corresponding area. The hip pain and
      imaging abnormalities resolved spontaneously following conservative treatment.
      This case study demonstrated that a subchondral fracture of the femoral head was
      associated with TOH using MRI and CT examinations, and suggests that the presence
      of a subchondral fracture may be important for the pathophysiology of TOH.

PMID- 17225153
TI  - MRI of rupture of the spring ligament complex with talo-cuboid impaction.
AB  - The spring ligament complex is essential for the stability of the longitudinal
      arch of the foot and includes the ligaments between the calcaneus and the talus
      at the superomedial to inferoplantar aspect of the foot. Tears of the spring
      ligament complex are most commonly degenerative in etiology and secondary to
      concomitant abnormality of the posterior tibial tendon. We report MRI findings in
      a 30-year-old man who presented with traumatic rupture of the spring ligament
      complex, seen following dislocation of the talonavicular joint. We also describe
      the previously unreported MRI features of talo-cuboid impaction secondary to
      disruption of the spring ligament complex.

PMID- 17225154
TI  - A marble in the small bowel.

PMID- 17225155
TI  - Correlation of sonographic findings and outcome in necrotizing enterocolitis.
AB  - BACKGROUND: There is little in the literature regarding the use of gray-scale and
      Doppler sonography of the bowel in necrotizing enterocolitis (NEC) and how
      findings depicted by this modality might assist in predicting outcome and
      influence management. OBJECTIVE: To correlate sonographic findings with outcome
      in NEC. MATERIALS AND METHODS: This was a retrospective analysis of clinical and
      abdominal ultrasonography (AUS) findings in NEC from January 2003 to December
      2005. AUS findings were evaluated for portal venous gas, free gas, peritoneal
      fluid, bowel wall thickness, echogenicity, perfusion and intramural gas. Patients
      were categorized into two groups, according to their outcome. RESULTS: A total of
      40 infants were identified who had AUS for NEC prior to any surgical
      intervention. Group A comprised 18 neonates treated medically and recovered
      fully, and group B comprised 22 neonates who required surgery or died. Free gas
      (six patients) and focal fluid collections (three patients) were only found in
      group B. Increased bowel wall echogenicity, absent bowel perfusion, portal venous
      gas, bowel wall thinning, bowel wall thickening, free fluid with echoes and
      intramural gas were seen in both groups, but more frequently in group B. Anechoic
      free fluid was seen more frequently in group A. Increased bowel perfusion was
      seen equally in both groups. CONCLUSION: An adverse outcome was associated with
      the sonographic findings of free gas, focal fluid collections or three or more of
      the following: increased bowel wall echogenicity, absent bowel perfusion, portal
      venous gas, bowel wall thinning, bowel wall thickening, free fluid with echoes
      and intramural gas. Sonographic findings are useful in predicting outcome and
      therefore might help guide management.

PMID- 17225156
TI  - Mesoherbivores reduce net growth and induce chemical resistance in natural
      seaweed populations.
AB  - Herbivory on marine macroalgae (seaweeds) in temperate areas is often dominated
      by relatively small gastropods and crustaceans (mesoherbivores). The effects of
      these herbivores on the performance of adult seaweeds have so far been almost
      exclusively investigated under artificial laboratory conditions. Furthermore,
      several recent laboratory studies with mesoherbivores indicate that inducible
      chemical resistance may be as common in seaweeds as in vascular plants. However,
      in order to further explore and test the possible ecological significance of
      induced chemical resistance in temperate seaweeds, data are needed that address
      this issue in natural populations. We investigated the effect of grazing by
      littorinid herbivorous snails (Littorina spp.) on the individual net growth of
      the brown seaweed Ascophyllum nodosum in natural field populations. Furthermore,
      the capacity for induced resistance in the seaweeds was assessed by removing
      herbivores and assaying for relaxation of defences. We found that ambient
      densities of gastropod herbivores significantly reduced net growth by 45% in
      natural field populations of A. nodosum. Seaweeds previously exposed to grazing
      in the field were less consumed by gastropod herbivores in feeding bioassays.
      Furthermore, the concentration of phlorotannins (polyphenolics), which have been
      shown to deter gastropod herbivores, was higher in the seaweeds that were exposed
      to gastropod herbivores in the field. This field study corroborates earlier
      laboratory experiments and demonstrates that it is important to make sure that
      the lack of experimental field data on marine mesoherbivory does not lead to rash
      conclusions about the lack of significant effects of these herbivores on seaweed
      performance. The results strongly suggest that gastropods exert a significant
      selection pressure on the evolution of defensive traits in the seaweeds, and that
      brown seaweeds can respond to attacks by natural densities of these herbivores
      through increased chemical resistance to further grazing.

PMID- 17225157
TI  - Getting to the fat of the matter: models, methods and assumptions for dealing
      with lipids in stable isotope analyses.
AB  - Within an organism, lipids are depleted in (13)C relative to proteins and
      carbohydrates (more negative delta(13)C), and variation in lipid content among
      organisms or among tissue types has the potential to introduce considerable bias
      into stable isotope analyses that use delta(13)C. Despite the potential for
      introduced error, there is no consensus on the need to account for lipids in
      stable isotope analyses. Here we address two questions: (1) If and when is it
      important to account for the effects of variation in lipid content on delta(13)C?
      (2) If it is important, which method(s) are reliable and robust for dealing with
      lipid variation? We evaluated the reliability of direct chemical extraction,
      which physically removes lipids from samples, and mathematical normalization,
      which uses the carbon-to-nitrogen (C:N) ratio of a sample to normalize delta(13)C
      after analysis by measuring the lipid content, the C:N ratio, and the effect of
      lipid content on delta(13)C (Deltadelta(13)C) of plants and animals with a wide
      range of lipid contents. For animals, we found strong relationships between C:N
      and lipid content, between lipid content and Deltadelta(13)C, and between C:N and
      Deltadelta(13)C. For plants, C:N was not a good predictor of lipid content or
      Deltadelta(13)C, but we found a strong relationship between carbon content and
      lipid content, lipid content and Deltadelta(13)C, and between and carbon content
      and Deltadelta(13)C. Our results indicate that lipid extraction or normalization
      is most important when lipid content is variable among consumers of interest or
      between consumers and end members, and when differences in delta(13)C between end
      members is <10-12 per thousand. The vast majority of studies using natural
      variation in delta(13)C fall within these criteria. Both direct lipid extraction
      and mathematical normalization reduce biases in delta(13)C, but mathematical
      normalization simplifies sample preparation and better preserves the integrity of
      samples for delta(15)N analysis.

PMID- 17225158
TI  - Convergence patterns and multiple species interactions in a designed plant
      mixture of five species.
AB  - It is known that convergence and divergence can occur in complex plant
      communities, but the relative importance of biotic and abiotic factors driving
      these processes is less clear. We addressed this issue in an experiment using a
      range of mixed stands of five species that are common in Swiss fens (Carex elata,
      C. flava, Lycopus europaeus, Lysimachia vulgaris and Mentha aquatica) and two
      levels of water and nutrients. One hundred and seventy-six experimental mixtures
      were maintained in large pots (75 l) for two consecutive growing seasons in an
      experimental garden. The stands varied systematically in the initial relative
      abundance of each of the five species and in overall initial stand abundance. The
      changes in biomass over 2 years were modelled as linear functions of treatments
      and the initial biomass of each species. The dynamics of the system were mainly
      driven by differences in the identity of species and by a negative feedback
      mechanism but also by different abiotic conditions. In all mixtures, C. elata
      became more dominant over time, which caused an overall convergence of community
      composition. In addition, the rate of change of each species' biomass was
      negatively related to its own initial abundance. Thus, a negative feedback
      further contributed to the convergence of communities. Species responded
      differently to water level and nutrient supply, causing community dynamics to
      differ among treatments. However, the different abiotic conditions only slightly
      modified the overall convergence pattern. Competitive interactions between more
      than two species were weaker than the negative feedback but still significantly
      influenced the species' final relative abundance. The negative feedback suggests
      that there is niche partitioning between the species, which permits their
      coexistence.

PMID- 17225159
TI  - Identification of CTL epitopes in hepatitis C virus by a genome-wide
      computational scanning and a rational design of peptide vaccine.
AB  - Developing a peptide-based vaccine for the highly variable hepatitis C virus
      (HCV) remains a challenging task. Variant viruses not only escape antigen
      presentation but also persist in a patient as quasi-species. Such variants are
      often antagonistic to the responding T cell repertoire. To overcome these
      problems, we herein propose a cocktail vaccine consisting of a few epitope
      peptides, which make it possible to outpace the emergence of variant viruses. To
      design such a vaccine, we developed a way to identify HLA-A*2402-binding peptides
      efficiently by means of the computational scanning of the whole genome of the
      pathogen. Most of the predicted peptides exhibited strong binding to the HLA
      A*2402 molecule, while also inducing CD8 T cell responses from the patients'
      peripheral blood mononuclear cells (PBMCs). Peptide-induced T cells were capable
      of lysing HCV-expressing HepG2 cells which process antigens endogenously. The
      amount of HCV core antigen in the patients' livers suggested that the lytic
      activity of the peptide-induced T cells was clearly in a range suitable for
      therapeutic use. If T cells were activated under optimal conditions by high
      density peptides, then they tended to be relatively tolerant of single amino acid
      variations for cytolysis. Finally, an analysis of the viral population isolated
      in Japan suggested no obvious changes due to immune evasion in the viral genome
      even in a host population highly biased toward HLA-A*2402.

PMID- 17225160
TI  - Arginine-vasopressin in neonates with vasodilatory shock after cardiopulmonary
      bypass.
AB  - Successful therapy of vasodilatory shock in adults and children with arginine
      vasopressin (AVP) has been reported previously. Data on the use of vasopressin in
      neonates is limited. This retrospective study reports the effects of AVP
      treatment in neonates with catecholamine-resistant systemic vasodilatation after
      cardiopulmonary bypass. From March 2003 through December 2005, 172 neonates
      underwent open-heart surgery, 17 developed vasopressor-resistant hypotension and
      were treated with AVP. Thirteen patients had a stage I palliation of single
      ventricle, two had a Ross-operation and two had an arterial switch operation. All
      patients received multiple traditional inotropes and vasopressors prior to
      administration of AVP. AVP was started at median 0.0001 U x kg(-1) x min(-1)
      (range 0.00005-0.0002) and titrated up to a maximum of median 0.0003 U x kg(-1) x
      min(-1) (range 0.0001-0.001). AVP led to a significant increase in blood pressure
      (from 49+/-8 mmHg to 69+/-7 mmHg) and the requirement of traditional vasopressors
      decreased significantly. No peripheral vasoconstriction or ischemia was observed.
      Four of 13 patients, all with single ventricle palliation, died. In two patients
      death occurred due to additional complications 6 days after AVP was discontinued.
      One patient, who was still on AVP, died 42 hours postoperatively after prolonged
      hypoxemia not responding to inhaled nitric oxide. One patient arrested on the
      third postoperative day when AVP was almost weaned. CONCLUSION: In neonates with
      vasodilatory shock after cardiopulmonary bypass AVP is a potent agent to increase
      blood pressure when traditional vasopressors are failing.

PMID- 17225161
TI  - Incidence, treatment, and outcome of severe sepsis in ICU-treated adults in
      Finland: the Finnsepsis study.
AB  - OBJECTIVE: To determine the incidence and outcome of severe sepsis in the adult
      Finnish population and to evaluate how treatment guidelines in severe sepsis are
      applied in clinical practice. STUDY DESIGN: A prospective study in 24 closed
      multidisciplinary ICUs in 21 hospitals (4 university and 17 tertiary hospitals)
      in Finland. PATIENTS: All 4,500 consecutive ICU admission episodes were screened
      for severe sepsis during a 4-month period (1 November 2004 - 28 February 2005).
      The referral population was 3,743,225. RESULTS: The severe sepsis criteria were
      fulfilled in 470 patients, who had 472 septic episodes. The incidence of severe
      sepsis in the ICUs in Finland was 0.38/1000 in the adult population (95%
      confidence interval 0.34-0.41). The mean ICU length of stay was 8.2+/-8.1 days.
      ICU, hospital, and 1-year mortality rates were 15.5%, 28.3%, and 40.9%,
      respectively. Respiratory failure requiring ventilation support was the most
      common organ failure (86.2%); septic shock was present in 77% and acute renal
      failure in 20.6% of cases. Activated protein C was given to only 15 of the 55
      patients with indication (27%) and low-dose corticosteroids to 150 of 366 (41%)
      patients with septic shock. CONCLUSIONS: This prospective study found the
      incidence of ICU-treated severe sepsis in Finland to be 0.38 per 1,000 of the
      population. The ICU and hospital mortalities were also lower than earlier
      reported in United States or Australia. Evidence-based sepsis therapies were not
      used as often as recommended.

PMID- 17225162
TI  - Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on
      cognitive performance and the EEG of young healthy male volunteers.
AB  - OBJECTIVES: The aim of this study was to get insight into the central effects of
      TC-1734 (renamed AZD3480), a selective agonist at the neuronal nicotinic receptor
      of the alpha4beta2 subtype. MATERIALS AND METHODS: Electroencephalography (EEG)
      techniques and computerized cognitive tests were performed in young, healthy male
      volunteers during two double-blind and placebo-controlled studies: a rising
      single dose crossover study (from 2 to 320 mg) and a rising repeated dose study
      with a parallel group design (50, 100, and 200 mg). RESULTS: In contrast to acute
      administration, administration of AZD3480 over 10 days produced statistically
      significant enhancement of several cognitive measures (attention and episodic
      memory) compared to placebo. Regarding EEG data, AZD3480 showed acceleration of
      the alpha centroid and of the alpha peak in the single-dose study. This EEG
      profile of the acceleration type was confirmed in the repeated dose study on both
      day 1 and day 10, with the greatest effect observed with the highest dose. The
      EEG pattern shown for AZD3480 was consistent with that previously described with
      other drugs known to improve attention and vigilance (including nicotine). In
      addition, subjects dosed with AZD3480 showed a statistically significant increase
      in mismatch negativity (MMN) amplitude at 50 and 200 mg while reducing MMN
      latency (200 mg only), suggesting an improvement of pre-attentional mechanisms.
      CONCLUSION: These early data in healthy subjects provide encouragement to
      consider development of AZD3480 as a novel agent for the treatment of cognitive
      decline in the elderly, including age-associated memory impairment and/or
      dementia of the Alzheimer's type.

PMID- 17225163
TI  - A translational, caffeine-induced model of onset insomnia in rats and healthy
      volunteers.
AB  - RATIONALE: Insomnia is a common and disabling complaint for which there is a need
      for improved treatments. Successful drug discovery relies on the use of
      appropriate animal models to assess likely outcome in the clinic. OBJECTIVES: The
      purpose of this study was to develop a translational, caffeine-induced model of
      insomnia in rats and healthy volunteers. We used sleep onset latency (SOL) as a
      comparable sleep measure between the two species. The model was validated by two
      effective sleep-promoting agents with different pharmacology, zolpidem and
      trazodone, which have GABA-ergic and serotonergic mechanisms, respectively.
      MATERIALS AND METHODS: In rats, radiotelemetry transmitters with
      electroencephalogram and electromyogram electrodes were implanted for sleep
      recording. Animals were administered with caffeine alone (10 mg/kg) or in
      combination with zolpidem (10 mg/kg) or trazodone (20 mg/kg), or vehicle, in
      crossover experiments. Home polysomnography was performed in 12 healthy male
      volunteers in a randomised, placebo-controlled, 4-week crossover study. Subjects
      received placebo, caffeine (150 mg) or caffeine in combination with zolpidem (10
      mg) or trazodone (100 mg). Subjective sleep effects in volunteers were assessed
      using the Leeds Sleep Evaluation Questionnaire. RESULTS: Caffeine caused a
      significant prolongation in objective SOL in rats and humans. This effect was
      sensitive to zolpidem and trazodone, both of which attenuated the caffeine
      induced increase in SOL. Furthermore, both hypnotics restored the disruption in
      subjective measures of sleep onset caused by caffeine in volunteers. CONCLUSIONS:
      This model therefore provides a promising paradigm in which we can study novel
      treatments for sleep disorders and an opportunity for direct comparison of
      results between rodents and humans.

PMID- 17225165
TI  - Propranolol blocks chronic risperidone treatment-induced enhancement of spatial
      working memory performance of rats in a delayed matching-to-place water maze
      task.
AB  - RATIONALE: Atypical antipsychotics improve cognitive function, including working
      memory, in schizophrenia. Some atypical antipsychotics have been reported to
      activate the locus coeruleus and induce beta-adrenoceptor antagonist sensitive c
      Fos-like immunoreactivity in the prefrontal cortex. MATERIALS AND METHODS: The
      present study investigated the effects of chronic treatment of rats with
      risperidone (1 mg kg(-1) day(-1) s.c.), clozapine (10 mg kg(-1) day(-1) s.c.), or
      acidified saline vehicle control for 2, 4, or 8 weeks on spatial working memory
      performance in a delayed matching-to-place water maze task with a 60-s inter
      trial retention interval with and without acute challenge with propranolol (10
      mg/kg i.p.). RESULTS: Treatment with risperidone for 8 weeks, but not 2 or 4
      weeks, significantly improved working memory performance. In contrast, treatment
      with clozapine for up to 8 weeks did not improve working memory. Acute challenge
      with propranolol blocked the improvement in working memory produced by chronic
      treatment with risperidone, but had no significant effect on performance in
      saline- or clozapine-treated animals. CONCLUSIONS: The delayed matching-to-place
      water maze task may prove valuable in the investigation of the behavioural
      pharmacology of the cognitive effects of antipsychotic drugs. These data suggest
      that beta adrenoceptors may contribute to the cognitive effects of chronic
      treatment with atypical antipsychotics.

PMID- 17225166
TI  - Sex differences in the potency of kappa opioids and mixed-action opioids
      administered systemically and at the site of inflammation against capsaicin
      induced hyperalgesia in rats.
AB  - RATIONALE: Sex differences in the potency of the antinociceptive effects of kappa
      opioids have been reported in various acute pain models with evidence suggesting
      that these sex differences are mediated by activity in the N-methyl-D: -aspartate
      (NMDA) system. OBJECTIVES: The purpose of the present study was to evaluate sex
      differences in the antihyperalgesic actions of selected kappa and mixed-action
      opioids in a persistent pain model and determine if the NMDA system modulates
      these effects in a sexually dimorphic manner. METHODS: Using gonadally intact
      male and female F344 rats, hyperalgesia was induced by local administration of
      capsaicin in the tail, after which the tail was immersed in a mildly noxious
      thermal stimulus (45 degrees C water), and tail-withdrawal latency measured.
      Opioids were then administered systemically (s.c.) and locally (in the tail)
      alone, and in selected combinations with the noncompetitive NMDA antagonist
      dextromethorphan. RESULTS: When administered systemically and locally, the kappa
      opioids spiradoline, U69,593 and U50,488, and the mixed-action opioids
      butorphanol and nalbuphine, produced dose-dependent antihyperalgesic effects.
      Whereas the kappa opioids were generally more potent in males, sex differences
      were not observed with the mixed-action opioids. Peripheral receptor activity was
      confirmed for local administration of kappa opioids by the antagonism observed
      after local, but not intracerebroventricular (i.c.v.), administration of the
      kappa antagonist nor-binaltorphamine (nor-BNI). Dextromethorphan was equally
      potent in attenuating the antihyperalgesia induced by kappa opioids in both males
      and females. CONCLUSIONS: These findings demonstrate sex differences in kappa
      opioid activity in a persistent pain model. Although an NMDA antagonist blocked
      the effects of kappa opioids in this model, these effects were not sexually
      dimorphic as reported in most acute pain models.

PMID- 17225164
TI  - Effort-related functions of nucleus accumbens dopamine and associated forebrain
      circuits.
AB  - BACKGROUND: Over the last several years, it has become apparent that there are
      critical problems with the hypothesis that brain dopamine (DA) systems,
      particularly in the nucleus accumbens, directly mediate the rewarding or primary
      motivational characteristics of natural stimuli such as food. Hypotheses related
      to DA function are undergoing a substantial restructuring, such that the classic
      emphasis on hedonia and primary reward is giving way to diverse lines of research
      that focus on aspects of instrumental learning, reward prediction, incentive
      motivation, and behavioral activation. OBJECTIVE: The present review discusses
      dopaminergic involvement in behavioral activation and, in particular, emphasizes
      the effort-related functions of nucleus accumbens DA and associated forebrain
      circuitry. RESULTS: The effects of accumbens DA depletions on food-seeking
      behavior are critically dependent upon the work requirements of the task. Lever
      pressing schedules that have minimal work requirements are largely unaffected by
      accumbens DA depletions, whereas reinforcement schedules that have high work
      (e.g., ratio) requirements are substantially impaired by accumbens DA depletions.
      Moreover, interference with accumbens DA transmission exerts a powerful influence
      over effort-related decision making. Rats with accumbens DA depletions reallocate
      their instrumental behavior away from food-reinforced tasks that have high
      response requirements, and instead, these rats select a less-effortful type of
      food-seeking behavior. CONCLUSIONS: Along with prefrontal cortex and the
      amygdala, nucleus accumbens is a component of the brain circuitry regulating
      effort-related functions. Studies of the brain systems regulating effort-based
      processes may have implications for understanding drug abuse, as well as energy
      related disorders such as psychomotor slowing, fatigue, or anergia in depression.

PMID- 17225167
TI  - Continuous exposure to the competitive N-methyl-D: -aspartate receptor
      antagonist, LY235959, facilitates escalation of cocaine consumption in Sprague
      Dawley rats.
AB  - RATIONALE: Chronic high dose consumption of cocaine is associated with
      significant negative effects to individual users and society. Nevertheless, the
      precise mechanisms that mediate increases in cocaine consumption in a drug-using
      individual are not fully understood. OBJECTIVES: This study used a long access
      version of the drug self-administration procedure to determine whether escalation
      of cocaine consumption is mediated by increased activity through N-methyl-D: 
      aspartate (NMDA) receptors. MATERIALS AND METHODS: Male Sprague-Dawley rats (n =
      63) were first trained to self-administer cocaine (0.33 mg/infusion, i.v.) under
      a fixed-ratio 1 schedule of reinforcement. After training, some rats were
      implanted with subcutaneous osmotic minipumps filled with vehicle or the
      competitive NMDA receptor antagonist, LY235959, and subsequently allowed to self
      administer cocaine in short (2 h) or long (6 h) access self-administration
      sessions. RESULTS: Vehicle-treated rats escalated cocaine self-administration
      across 14 long-access self-administration sessions. Rats treated with LY235959
      via osmotic minipump, but not twice daily injections, escalated cocaine self
      administration at a greater rate and to a greater degree than vehicle-treated
      rats. In post-escalation cocaine dose-infusion tests, rats treated continuously
      with LY235959 self-administered more cocaine (0.08-1.32 mg/infusion) than vehicle
      treated rats, regardless of access condition, shifting the dose-infusion curves
      upward. During extinction sessions, which were conducted after the escalation
      phase of the study, rats that had long (6 h) access to cocaine stopped responding
      sooner than rats that had short (2 h) access to cocaine, independent of LY235959
      treatment. CONCLUSIONS: These data are consistent with hypo-glutamatergic
      consequences of repeated cocaine exposure.

PMID- 17225168
TI  - Involvement of group II metabotropic glutamate receptors in stress-induced
      behavioural sensitization.
AB  - RATIONALE: A short session of repeated foot shocks in rats causes long-lasting
      sensitization of behavioural, hormonal and autonomic responses to novel stressful
      challenges. The behavioural sensitization can be reduced by anxiolytics and
      mimics aspects of stress-induced changes in patients with post-traumatic stress
      disorder. OBJECTIVES: The aim of this study was to test the efficacy of a group
      II metabotropic glutamate receptor (mGluR) agonist and assess altered brain mGluR
      receptor expression in shock-sensitized rats. MATERIALS AND METHODS: Male Wistar
      rats were exposed to a 15-min session with ten 6-s foot shocks (preshocked). One
      and 2 weeks later, rats were intraperitoneally injected with the group II
      metabotropic glutamate receptor agonist (2R,4R)-4-aminopyrrolidine-2,4
      dicarboxylate (APDC) or vehicle, and 30 min later exposed to 5 min of 85 dB
      noise. For in situ hybridization with probes for mGluR1, mGluR2, mGluR3 and
      mGluR5, preshocked and control rats were killed under basal conditions 2 weeks
      after foot shocks and their brains cryosectioned. RESULTS: APDC had no clear
      effect in controls, but dose-dependently reduced high immobility and increased
      low locomotion and rearing seen in preshocked rats to the levels of controls.
      mGluR3 expression was increased in the basolateral nucleus of the amygdala, and
      mGluR2 expression was increased in the agranular insular cortex of preshocked
      rats compared to controls. CONCLUSIONS: Shock-induced behavioural sensitization
      in rats is reduced by acute treatment with a group II metabotropic glutamate
      receptor agonist. This effect may depend on the increased expression of amygdala
      mGluR3, which could be hypothesized as an endogenous mechanism to counteract
      stress-induced neuronal sensitization.

PMID- 17225171
TI  - Decreased cyclin-dependent kinase activity promotes thyroid hormone-dependent
      tail regression in Rana catesbeiana.
AB  - The thyroid hormone (TH), 3,5,3'-triiodothyronine (T(3)), is an important
      regulator of diverse cellular processes including cell proliferation,
      differentiation, and apoptosis, with increasing evidence that the modulation of
      the phosphoproteome is an important factor in the TH-mediated response. However,
      little is understood regarding the mechanisms whereby phosphorylation may
      contribute to T(3)-mediated cellular outcomes during development. The cyclin
      dependent kinases (Cdks) and mitogen-activated protein kinases (MAPK/ERK) have
      been implicated in TH signaling in mammalian cells. In this study, we have
      investigated, in frogs, the possible role that these kinases may have in the
      promotion of tail regression during tadpole metamorphosis, an important
      postembryonic process that is completely TH-dependent. Cdk2 steady state levels
      and activity increase in the tail concurrent with progression through the growth
      phase of metamorphosis, followed by a precipitous decrease coinciding with tail
      regression. Cyclin-A-associated kinase activity also follows a similar trend
      except that its associated kinase activity is maintained longer before a decrease
      in activity. Protein steady state levels of ERK1 and ERK2 remain relatively
      constant, and their kinase activities do not decrease until much later during
      tail regression. Tail tips cultured in serum-free medium in the presence of T(3)
      undergo regression, which is accelerated by coincubation with a specific Cdk2
      inhibitor. Coincubation with PD098059, a MAPK inhibitor, has no effect. Thus,
      T(3)-dependent tail regression does not require MAPKs, but a decrease in Cdk2
      activity promotes tail regression.

PMID- 17225169
TI  - Glia mechanisms in mood regulation: a novel model of mood disorders.
AB  - INTRODUCTION: Recent evidence in clinical and preclinical studies has implicated
      glutamate neurotransmissions in pathophysiology of mood disorders. The regulation
      of amino acid neurotransmission, i.e., glutamate and gamma-aminobutyric acid
      (GABA) involves coordinated mechanisms of uptake and transport within a
      tripartite synaptic system that includes neurons and glia. Newly appreciated role
      of the glia, more specifically astrocytes on neuronal functions combined with
      reported postmortem abnormalities of glia in patients with mood disorders further
      supports the role of glia in mood disorders. MATERIALS AND METHODS: This report
      presents some of our preliminary results utilizing glia-selective toxins and
      other pharmacological tools to suppress glial function within the limbic system
      to study the resulting behavioral abnormalities, and thus, elucidate glial
      involvement in the development of mood disorders. RESULTS AND DISCUSSION: We
      demonstrate that chronic blockade of glutamate uptake by a glial/neuronal
      transporter antagonist L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) within the
      amygdala, a key area implicated in mood regulation, results in dose-dependent
      reduction in social exploratory behavior and disrupts circadian activity patterns
      consistent with symptoms of mood disorders. Similarly, the selective astrocytic
      glutamate transporter type 1 (GLT-1) blocker dihydrokainic acid (DHK) injected
      into the amygdala also results in reduced social interaction that is blocked by
      selective glutamate N-methyl-D-aspartate (NMDA) type receptor antagonist AP5. The
      results are discussed in the context of glial and glutamate mechanisms in mood
      disorders and potential therapeutic avenues to address these mechanisms.

PMID- 17225172
TI  - Haematopoiesis in snakes (Ophidia) in early postnatal development.
AB  - The occurrence of haematopoiesis has been studied in various parts of the spine
      and in the ribs in four species of snakes (Boa constrictor L., Elaphe guttata L.,
      Lamprophis fulaginosus Boie., Bothrops jararaca Wied.) from hatching until 150
      days of postnatal development. Marrow spaces are formed by chondrolysis with
      various time frames depending on the studied species. Marrow cells egress to the
      general circulation in two ways: via migration through the endothelial cells
      lining the venous sinuses or by the rupture of protrusions. Erythroblasts are
      present in the lumen of marrow sinuses suggesting their final maturation there.
      Various relationships of the spleen to the pancreas have been found. No
      myelopoietic foci occur in the spleen, liver or kidney of any of the studied
      species. However, erythropoiesis (sparse islets) has been observed in Bothrops
      jararaca spleen.

PMID- 17225170
TI  - Accumbens neurochemical adaptations produced by binge-like alcohol consumption.
AB  - RATIONALE: The Scheduled High Alcohol Consumption (SHAC) binge drinking model is
      a simple, partial murine model with which to investigate some of the
      neurobiological underpinnings of alcoholism. OBJECTIVES: The SHAC model was used
      to characterize monoamine and amino acid adaptations produced in the nucleus
      accumbens (NAC) by repeated bouts of high alcohol consumption. METHODS: In vivo
      microdialysis was conducted in the NAC of C57BL/6J (B6) mice during consumption
      of water, a 5% alcohol (v/v) solution for the first time (SHAC1) or a 5% alcohol
      solution for the sixth time (SHAC6). A second set of microdialysis experiments
      assessed the neurotransmitter response to an alcohol challenge injection (1.5 or
      2 g/kg, IP). RESULTS: In both drinking experiments, SHAC1 and SHAC6 mice consumed
      comparable amounts of alcohol during the 40-min period of alcohol availability
      (approximately 1.5 g/kg) and total fluid intake was similar between water and
      SHAC1/6 mice. Despite the similarity in alcohol consumption, alcohol-mediated
      increases in the extracellular concentration of GABA and serotonin were reduced,
      but glutamate was increased in the NAC of SHAC6 mice, relative to SHAC1 animals.
      No differences were observed in extracellular dopamine between SHAC1 and SHAC6
      mice during alcohol consumption. After alcohol injection, SHAC6 mice also
      exhibited sensitized glutamate release, but did not differ from water or SHAC1
      animals for any of the other neurotransmitters examined. Brain alcohol
      concentrations did not differ between groups after injection. CONCLUSIONS:
      Repeated bouts of high alcohol consumption induce an imbalance between inhibitory
      and excitatory neurotransmission within the NAC that may drive excessive drinking
      behavior.

PMID- 17225173
TI  - Second-look arthroscopy after arthroscopy-assisted treatment of tibial plateau
      fractures.
AB  - The only way to show the healing potential in hyaline cartilage after the
      treatment of tibial plateau fractures in humans is the second-look arthroscopy.
      Our aim is to examine the healing potential of the hyaline cartilage in tibial
      plateau fractures treated with arthroscopy-assisted surgery. We applied second
      look arthroscopy to the 12 patients out of 52 who had tibial plateau fractures
      treated by arthroscopy-assisted surgery. The mean age was 41. The tibial plateau
      fractures were classified according to Schatzker classification. The period
      between the primary surgical treatment and second-look arthroscopy was on an
      average of 19 months. Step-off was detected in 3 out of 12 patients. Hyaline
      cartilage of nine patients who did not have step-off was found obviously on the
      fracture line. None of them had displacement. Three patients out of 12 were above
      50 years old and the average follow-up period was 26 months. Grade II-III
      chondral defect was detected on the fracture line and femoral condyle in patients
      above 50 years. For patients below 50 years old, the follow-up period was 21
      months and grade I-II chondral defect was detected on the fracture line and
      femoral condyle. Until now in literature, tibial plateau fractures have been
      evaluated clinically and radiologically, but in our cases we directly saw the
      lesion. Cartilage healing is limited in human beings. On the fracture line,
      cartilage defect continues, although anatomic reduction has been achieved.
      Moreover, if there is step-off, insufficient healing potential appears. Although
      we did not have enough cases, we can say that in tibial plateau fractures
      anatomic reduction is mandatory. Contrary to the common idea, step-off is not
      tolerated by hyaline cartilage.

PMID- 17225174
TI  - Bilateral symptomatic discoid medial meniscus: report of three cases.
AB  - Discoid medial meniscus is very rare and bilateral discoid medial meniscus is
      extremely rare. We report symptomatic bilateral discoid meniscus with abnormal
      attachment to anterior cruciate ligament (ACL) in three patients and we think
      that our report is a combination of very rare conditions. The patients had
      symptoms in both sides and we performed magnetic resonance imaging (MRI) and
      operated five knees. The operation methods were different by the condition of
      menisci.

PMID- 17225175
TI  - Patellar tendon length after anterior cruciate ligament reconstruction: a
      comparative magnetic resonance imaging study between patellar and hamstring
      tendon autografts.
AB  - Patellar tendon shortening after anterior cruciate ligament reconstruction may be
      associated with anterior knee pain or patellofemoral arthritis. The present study
      was designed to compare postoperative changes in patellar tendon length after
      anterior cruciate ligament reconstruction between patellar tendon and hamstring
      tendon autograft. Magnetic resonance images of both knees (operated and healthy)
      and functional outcome were documented at least 1 year postoperatively in 16
      patellar tendon harvested patients and in 32 hamstrings harvested patients.
      Patellar tendon length, patella length and Insall-Salvati ratio were measured.
      The operated knee values were compared to the respective values of the non
      operated control knees. A significant 4.2 mm or 9.7% patellar tendon shortening
      in patellar tendon group and a non-significant 1.14 mm or 2.6% shortening in
      hamstrings group was detected. No significant difference was detected in terms of
      major shortening-patella baja-(6% for the patellar tendon group vs. 0% for the
      hamstring group). There was no significant difference in anterior knee problems
      between the two groups as evidenced by the Shelbourne score (94 for the patellar
      tendon group vs. 98 for the hamstring group). Harvesting of the patellar tendon
      for anterior cruciate ligament reconstruction resulted in a significant
      shortening of the remaining tendon. In contrast harvesting of the hamstring
      tendons did not affect significantly the patellar tendon length. However, the
      incidence of patella baja and overall functional outcome was not significantly
      different between the two groups.

PMID- 17225176
TI  - Assessment of normal ACL double bundle anatomy in standard viewing planes by
      magnetic resonance imaging.
AB  - Anatomical studies show that the native ACL consists of two distinct functional
      bundles, termed the anteromedial (AM) and posterolateral (PL) bundles. The
      utility of using routine magnetic resonance imaging (MRI) to distinguish the
      individual bundles of the ACL has not been evaluated. The purpose of this study
      was to evaluate the intra- and inter-observer agreement for assessment of the AM
      and PL bundles using MRI in the axial, coronal, and sagittal viewing planes. We
      identified a series of patients seen in the senior author's clinic during a 16
      month period. Images were independently evaluated in blinded fashion at two
      separate time points by a musculoskeletal radiologist and two orthopaedic
      residents. The AM bundle was detected in most planes of view with high frequency
      and reliability, while detection of the PL bundle was less frequent and had a
      lower associated reliability. Our results indicate that it is difficult to
      reliably detect both the AM and PL bundles using a low-field strength magnet with
      standard planes of view. It has been demonstrated that the ACL may be imaged
      effectively in planes that are based on the natural course of the ligament, and
      it is likely that this will also facilitate visualization of the individual AM
      and PL bundles. The use of additional oblique planes of view offers a potential
      approach for improved evaluation of the ACL, even with low field strength
      magnets. Future work in this area may assist in the pre-operative assessment of
      isolated AM or PL bundle injuries, facilitating a more anatomic approach to ACL
      reconstruction.

PMID- 17225177
TI  - Clinical, radiologic and arthroscopic assessment and treatment of bilateral
      discoid lateral meniscus.
AB  - The purpose of the study is to evaluate clinical, radiologic and arthroscopic
      features of bilateral discoid lateral meniscus and to assess the outcome of
      arthroscopic meniscectomy. Among the 177 arthroscopies performed for discoid
      lateral meniscus between January 1993 and January 2004, 12 were bilateral. The
      clinical and radiologic evaluation was done from the records. The type of discoid
      meniscus, the type of tear was assessed arthroscopically. All patients underwent
      arthroscopic meniscectomy. Patients were followed up for a minimum period of 2
      years. All patients had pain as presenting symptom. Eight patients presented with
      bilateral knee pain and four patients developed pain in the opposite knee after
      the affected knee was treated. The classically described thud was present in 11
      knees. The widening of the joint space was found in 13 knee radiographs; 14 knees
      had complete type, nine had incomplete type and one had ring type of discoid
      lateral meniscus on arthroscopic evaluation; 20 knees involving 10 complete
      types, all incomplete types and ring type of discoid lateral meniscus showed
      obvious meniscal tears. The remaining four meniscus showed softening of a portion
      of the meniscus. Underlying intra-substance tear was visualized arthroscopically
      in the softened areas on saucerisation. All but one discoid menisci underwent
      arthroscopic partial central meniscectomy. When followed up for an average period
      of 32.6 months 19 knees showed excellent results and 5 knees good results.
      Possibility of bilaterality should be suspected in discoid lateral meniscus.
      Softening of meniscus denotes underlying intra-substance tear. This finding has
      not been described in the literature so far. Arthroscopic partial meniscectomy
      gives good results in symptomatic bilateral discoid meniscus. This to our
      knowledge is the largest series of bilateral discoid lateral menisci.

PMID- 17225178
TI  - Dynamic measurement of patellofemoral kinematics and contact pressure after
      lateral retinacular release: an in vitro study.
AB  - The purpose of this study was to investigate the influence of lateral retinacular
      release and medial and lateral retinacular deficiency on patellofemoral position
      and retropatellar contact pressure. Human knee specimens (n = 8, mean age = 65 SD
      7 years, all male) were tested in a kinematic knee-simulating machine. During
      simulation of an isokinetic knee extension cycle from 120 degrees to full
      extension, a hydraulic cylinder applied sufficient force to the quadriceps tendon
      to produce an extension moment of 31 Nm. The position of the patella was measured
      using an ultrasound based motion analysis system (CMS 100, Zebris). The amount of
      patellofemoral contact pressure and its pressure distribution was measured using
      a pressure sensitive film (Tekscan, Boston). Patellar position and contact
      pressure were first investigated in intact knee conditions, after a lateral
      retinacular release and a release of the medial and lateral retinaculum. After
      lateral retinacular release the patella continuously moved from a significant
      medialised position at flexion (P = 0.01) to a lateralised position (P = 0.02) at
      full knee extension compared to intact conditions, the centre of patellofemoral
      contact pressure was significantly medialised (0.04) between 120 degrees and 60
      degrees knee flexion. Patellofemoral contact pressure did not change
      significantly. In the deficient knee conditions the patella moved on a
      significant lateralised track (P = 0.04) through the entire extension cycle with
      a lateralised centre of patellofemoral pressure (P = 0.04) with a trend (P =
      0.08) towards increased patellofemoral pressure. The results suggest that lateral
      retinacular release did not inevitably stabilise or medialise patellar tracking
      through the entire knee extension cycle, but could decrease pressure on the
      lateral patellar facet in knee flexion. Therefore lateral retinacular release
      should be considered carefully in cases of patellar instability.

PMID- 17225179
TI  - The value of magnetic resonance imaging in our current management of ACL and
      meniscal injuries.
AB  - Magnetic resonance imaging (MRI) is frequently used in the diagnosis of anterior
      cruciate ligament (ACL) and meniscal injuries. The aim of this retrospective
      study was to determine the reliability and value of MRI in our management of ACL
      and meniscal tears. 138 patients who had undergone a MRI to confirm or refute the
      clinical diagnosis of an ACL or meniscal tear were identified. Those who had
      subsequently undergone arthroscopy were selected. MRI findings and clinical
      diagnosis were compared with those at arthroscopy. Sensitivity, specificity,
      positive predictive value (PPV), negative predictive value (NPV) and overall
      accuracy of clinical diagnosis and MRI were then calculated. The overall accuracy
      for MRI was 91, 68 and 86% for detecting ACL, medial meniscal and lateral
      meniscal tears, respectively. Accuracy for clinical diagnosis was 90 and 64% for
      ACL and meniscal tears, respectively. In contrast to other series, our results
      indicate a lower accuracy of MRI in detecting pathology, especially of the ACL
      and medial meniscus. We noted a low sensitivity, specificity and positive
      predictive value but a high negative predictive value rendering MRI most useful
      as a negative diagnostic tool. We suggest that where symptoms and clinical
      findings support one of these diagnoses and arthroscopic therapeutic intervention
      is contemplated, that MRI scanning is not always beneficial. Our current practice
      of requesting scans to routinely confirm the diagnosis should be altered.
      Unnecessary MRI scanning increases the financial burden and delays patient
      treatment.

PMID- 17225180
TI  - Gallbladder mucin production and calcium carbonate gallstones in children.
AB  - In contrast to adults, calcium carbonate gallstones are relatively common in
      children. Their pathogenesis is poorly understood. Cystic duct obstruction
      promotes calcium carbonate formation in bile and increases gallbladder mucin
      production. We tested the hypothesis that mucin producing epithelial cells would
      be increased in gallbladders of children with calcium carbonate gallstones.
      Archival gallbladder specimens from 20 consecutive children who had undergone
      elective cholecystectomy for cholelithiasis were examined. In each case,
      gallstone composition was determined by Fourier transform infrared
      microspectroscopy. Gallbladder specimens from six children who had undergone
      cholecystectomy for conditions other than cholelithiasis during the same period
      were used as controls. Multiple sections were examined in a blinded fashion and
      scored semiquantitatively for mucin production using two stains (alcian blue and
      periodic acid-Schiff). Increased mucin staining was observed in 50% or more
      epithelial cells in five gallbladder specimens from seven children with calcium
      carbonate stones, compared to 5 of 13 with other stone types (P = 0.17) and none
      of the control gallbladders (P = 0.02). Gallbladders containing calcium carbonate
      stones were significantly more likely than those containing other stone types or
      controls to contain epithelial cells with the greatest mucin content (P = 0.03).
      Gallbladders containing calcium carbonate stones were also more likely to show
      the ulcer-associated cell lineage. These results demonstrate an increase in mucin
      producing epithelial cells in gallbladders from children containing calcium
      carbonate stones. This supports the hypothesis that cystic duct obstruction
      leading to increased gallbladder mucin production may play a role in the
      development of calcium carbonate gallstones in children.

PMID- 17225181
TI  - Leucine-rich repeat kinase 1: a paralog of LRRK2 and a candidate gene for
      Parkinson's disease.
AB  - Leucine-rich repeat kinase 1 gene (LRRK1) on chromosome 15q26.3 is a paralog of
      LRRK2 in which multiple substitutions were recently linked to Parkinson's
      disease. We have examined the exon-intron structure of the gene and the expressed
      mRNA sequence in brain. LRRK1 sequencing analysis in 95 probands from families
      with autosomal dominant Parkinson's disease identified 23 variants, 14 of which
      are novel, with four resulting in non-synonymous amino acid substitutions. These
      four substitutions are rare and do not clearly segregate with disease within our
      families or associate with sporadic Parkinson's disease in a US case-control
      series. Subsequent sequencing of exon 26 encoding the kinase activation segment
      in an additional 360 probands identified one further synonymous variant,
      suggesting that LRRK1 variants are not a frequent cause of Parkinson's disease.
      The relative absence of substitutions within LRRK1 highlights a greater
      conservation of sequence than observed for LRRK2. Comparison of evolutionary
      interspecies sequences of LRRK1 and LRRK2 suggests they diverged from a common
      founder gene.

PMID- 17225182
TI  - [18F-FDG-PET in therapy response of esophageal cancer].
AB  - PET imaging with the glucose analog fluorodeoxyglucose (FDG-PET) has been
      evaluated in several studies to monitor tumor response in patients undergoing
      chemo- and radiotherapy. The clinical value of FDG-PET for differentiation of
      residual tumor and therapy induced fibrosis has been documented for esophageal
      cancer. Furthermore, there are now several reports suggesting that quantitative
      assessment of therapy induced changes in tumor FDG-uptake may allow prediction of
      tumor response and patient outcome very early in the course of therapy. This
      suggests that FDG-PET may be used to identify non-responders early during
      neoadjuvant chemoradiotherapy allowing for early modifications of the treatment
      protocol.

PMID- 17225183
TI  - [Interstitial pneumonias].

PMID- 17225184
TI  - [Imaging of emphysema].
AB  - Emphysema is defined as a condition of the lung characterized by abnormal,
      permanent enlargement of airspaces distal to the terminal bronchiole accompanied
      by destruction of the alveolar walls and without obvious fibrosis. It is a very
      common disease with high morbidity and mortality. Histopathologically, there are
      two types of emphysema: panlobular emphysema, typically occurring in alpha1
      antitrypsin deficiency, and centrilobular emphysema, which is strongly associated
      with cigarette smoking. Computed tomography (CT) allows detection of emphysema
      with higher sensitivity than conventional chest radiography and pulmonary
      function tests. CT also allows quantification of emphysema and depicts associated
      changes and complications. The differential diagnosis of emphysema, which is
      characterized by the absence of clearly definable walls on CT, includes cystic
      lung disease, bullae, lung laceration, Langerhans cell histiocytosis, and
      lymphangioleiomyomatosis -which are all characterized by visible walls on CT.

PMID- 17225185
TI  - [Radiologic diagnosis of lung tuberculosis].
AB  - The radiologic knowledge of tuberculosis-associated lung disease is an essential
      tool in the clinical diagnosis of tuberculosis. Chest radiography is the primary
      imaging method, but the importance of CT is still increasing, as CT is more
      sensitive in the detection of cavitation, of hilar and mediastinal
      lymphadenopathie, of endobronchial spread and of complications in the course of
      the disease. In addition, CT has been proven as a valuable technique in the
      assessment of tuberculosis activity, especially in patients where M. tuberculosis
      has not been detected in the sputum or in patients with multidrug-resistant
      tuberculosis. Depending on the immune status of the patient, the morphologic
      spectrum of tuberculosis is quite variable. Early diagnosis of tuberculosis is
      essential to prevent further spread of the disease.

PMID- 17225186
TI  - [MSCT for staging and response evaluation of esophageal cancer].
AB  - Squamous cell carcinomas and adenocarcinomas account for the majority of cases of
      esophageal cancer. Esophageal cancer often is diagnosed in advanced stages as
      clinical symptoms are lacking in early stages. The major aims of imaging in
      esophageal cancer are to determine local tumor extension (T and N staging), to
      rule out systemic disease (M staging), and to assess response to neoadjuvant
      therapy (response evaluation). CT is still inferior to endoscopic ultrasound in
      differentiating T stages and detecting regional lymph node metastases. However,
      it plays a central role in determining infiltration into adjacent organs (T4
      stage) and in ruling out distant metastases. Multislice-CT (MSCT) offers the
      possibility of reconstructions, which often help to assess the relationship
      between tumor and anatomic landmarks like the tracheobronchial tree or the
      diaphragm. First results of CT volumetry for response evaluation are promising;
      however, PET and PET/CT with the glucose analogue FDG are the standard methods to
      evaluate response to neoadjuvant therapy.

PMID- 17225187
TI  - Changes of bone mineral density after cementless total hip arthroplasty with two
      different stems.
AB  - Cementless total hip arthroplasty has achieved reliable long-term results since
      porous coatings were developed, but postoperative changes around the stem remain
      poorly documented. In this study, changes of the bone mineral density (BMD) were
      compared between two types of cementless stem. In group B (28 patients with 31
      hips), a straight tapered stem with porous plasma spray coating on the proximal
      1/4 was used, while group S (24 patients with 26 hips) was given a fluted, tri
      slot stem with porous hydroxyapatite coating on the proximal 1/3. In group B,
      there was an early decrease of BMD, which recovered after 12 months, indicating
      that stress shielding was minimal. In group S, however, BMD continued to decrease
      without recovery. The stem shape and radiological findings suggested that the
      cause of stress shielding in group S was distal fixation.

PMID- 17225188
TI  - Hormonal profiles and biochemical indices of bone turnover in Indian women.
AB  - The study establishes Indian referent database for bone turnover markers. The
      levels of markers decreased across the four quartiles of BMD showing a negative
      correlation with BMD. The study depicts that levels of hormones and bone turnover
      makers can aid in identifying women at risk for osteoporosis. INTRODUCTION:
      Biochemical markers of bone turnover reflect changes in bone metabolism earlier
      and aid in the management of osteoporosis. Since a referent database for Indian
      women is lacking, the study was initiated to establish the same and suggest that
      hormonal profiles and markers of bone turnover can aid in identifying women at
      risk for osteoporosis. METHODS: Osteocalcin (OC), bone specific alkaline
      phosphatase ((BSAP), C-terminal crosslinking telopeptide of type-I collagen (CTX
      I), deoxypyridinoline (DPD), follicle-stimulating hormone (FSH) and estrone
      glucuronide (E(1)G) were measured in 365 Indian women (20-70 years) and
      correlated with BMD measurements by dual energy absorptiometry (DXA) using one
      way analysis of variance (ANOVA). RESULTS: The mean levels of bone resorption
      markers; CTX-I and DPD increased significantly across the age showing a negative
      correlation with BMD. The increase in levels of CTX-I and DPD was significantly
      higher (p < 0.0001) as compared to the femoral and spinal BMD, which dropped only
      30-36%. The levels of bone turnover markers and FSH decreased across the four
      quartiles of spinal and femoral BMD showing a negative correlation whereas E(1)G
      levels increased across the four quartiles. CONCLUSION: The bone turnover markers
      were comparatively low in cohort of Indian women studied.

PMID- 17225189
TI  - Beneficial effect of DL-alpha-lipoic acid on cyclosporine A induced
      hyperlipidemic nephropathy in rats.
AB  - Cyclosporine A (CsA)-induced dyslipidemia is one of the most important risk
      factors for morbidity and mortality after solid organ transplantation. Reducing
      this side effect of CsA by dietary agents may be safe, cost-effective, and
      attractive to both patients and health professionals. Hence the present study was
      designed to evaluate the role of DL-alpha-Lipoic acid (LA) in deteriorating the
      lipid abnormalities induced by CsA in rat kidney. Male albino Wistar rats were
      divided into four groups. CsA administered at a dose of 25 mg/kg body weight,
      orally for 21 days showed abnormal changes in the levels of lipoprotein fractions
      (LDL, HDL and VLDL) and lipid profile in both plasma and renal tissue.
      Significant alterations were also observed in the activities of lipid
      metabolizing enzymes. Co-treatment with LA (20 mg/kg body weight, oral gavage,
      for 21 days) reverted the levels of lipid profile (P < 0.001, P < 0.01) and
      lipoprotein fractions (P < 0.001, P < 0.01) to near control. The activities of
      lipid metabolizing enzymes also showed considerable restoration on LA
      supplementation. The outcome of this study provides evidence that LA (a natural
      metabolic antioxidant) treatment acts as a potent antilipemic agent against CsA
      induced lipid abnormalities.

PMID- 17225190
TI  - Inhibition of nitric oxide synthase enhances contractile response of ventricular
      myocytes from streptozotocin-diabetic rats.
AB  - The contractile hyporesponsiveness of the streptozotocin diabetic rat heart in
      vitro to beta-adrenergic agonists is eliminated when the heart is perfused with
      N(G)-nitro-L-arginine methyl ester (L-NAME), a non-selective inhibitor of nitric
      oxide synthase (NOS). The following study evaluated the hypothesis that an
      increased production of NO/cGMP within the diabetic myocyte inhibits the beta
      adrenergic-stimulated increase in calcium current and contractile response. Male
      Sprague-Dawley rats were given an intravenous injection of streptozotocin (60
      mg/kg). After 8 weeks, L-type calcium currents were recorded in ventricular
      myocytes using the whole cell voltage-clamp method. Shortening of isolated
      myocytes was determined using a video edge detection system. cAMP and cGMP were
      measured using radioimmunoassay. Nitric oxide production was determined using the
      Griess assay kit. Basal cGMP levels and nitric oxide production were elevated in
      diabetic myocytes. Shortening of the diabetic myocytes in response to
      isoproterenol (1 microM) was markedly diminished. However, there was no
      detectable difference in the isoproterenol-stimulated L-type calcium current or
      cAMP levels between control and diabetic myocytes. Acute superfusion of the
      diabetic myocyte with L-NAME (1 mM) decreased basal cGMP and markedly enhanced
      the shortening response to isoproterenol but did not alter isoproterenol
      stimulated calcium current. These data suggest that increased production of
      NO/cGMP within the diabetic myocyte suppressed beta-adrenergic stimulated
      shortening of the myocyte. However, NO/cGMP apparently does not suppress
      shortening of the myocyte by inhibition of the beta-stimulated calcium current.

PMID- 17225191
TI  - Patterns and associations of body weight among older adults in two Asian
      societies.
AB  - Body weight has important health implications across the lifespan. Most recent
      attention has focused on the obesity epidemic that is occurring in many parts of
      the world. However, underweight is also a concern, particularly in less developed
      countries. For most health outcomes there is a curvilinear association with body
      weight, with underweight and overweight (compared to normal weight) being
      associated with a higher prevalence of chronic debilitating and life-threatening
      conditions and ultimately mortality. This paper uses data from two nationally
      representative surveys of older adults (aged 60 and older) in the Philippines
      (1996) and Taiwan (1999) to assess the prevalence of underweight and overweight
      and examine associations between body weight and demographic, socioeconomic, and
      health characteristics in these populations. Older Filipinos have a modest
      prevalence of underweight (29.9%) and low prevalence of overweight (12.2%),
      whereas the reverse is observed in Taiwan (6.4 and 29.3%, respectively). Results
      show generally expected associations between body weight and demographic
      characteristics, health conditions and behaviors. We find little evidence of
      socioeconomic differences in body weight, except in the Philippines where higher
      SES is associated with a lower risk of being underweight. Implications of the
      results are discussed in terms of healthy weight maintenance among critical
      subgroups to potentially reduce the prevalence of disease and improve quality of
      life.

PMID- 17225192
TI  - Unruly grandmothers, ghosts and ancestors: Chinese elders and the importance of
      culture in dementia evaluations.
AB  - This article explores the cultural clashes that occurred when Chinese patients at
      an Alzheimer's center in California were evaluated for dementia. Lack of
      familiarity with Chinese culture made the culturally mainstream American
      clinicians at this center more likely to misinterpret the behavior of elderly
      Chinese-speaking patients and their families and, thereby, more likely to
      misdiagnose such patients and suggest culturally inappropriate recommendations.
      This tendency was reduced when relevant cultural knowledge was incorporated into
      the clinical evaluation. The evaluation process at this clinic and two patient
      examples are discussed to illustrate that familiarity with a patient's cultural
      background is essential for accurate diagnosis and referral. This ethnographic
      case study places the evaluation process in one particular clinic in cultural
      context and is suggestive in the way that exploratory qualitative research is
      meant to be, rather than broadly representative of dementia clinics or clinicians
      as a whole. However, problems created by cultural clashes at this clinic do
      suggest that what may be happening at other dementia clinics as they encounter
      increasingly more patients from diverse cultural backgrounds is an important
      empirical question worthy of further research, using both qualitative and
      quantitative methods.

PMID- 17225193
TI  - The effect of the balance of orthographic neighborhood distribution in visual
      word recognition.
AB  - The present study investigated whether the balance of neighborhood distribution
      (i.e., the way orthographic neighbors are spread across letter positions)
      influences visual word recognition. Three word conditions were compared. Word
      neighbors were either concentrated on one letter position (e.g.,nasse/basse-lasse
      tasse-masse) or were unequally spread across two letter positions
      (e.g.,pelle/celle-selle-telle-perle), or were equally spread across two letter
      positions (e.g.,litre/titre-vitre-libre-livre). Predictions based on the
      interactive activation model [McClelland & Rumelhart (1981). Psychological
      Review, 88, 375-401] were generated by running simulations and were confirmed in
      the lexical decision task. Data showed that words were more rapidly identified
      when they had spread neighbors rather than concentrated neighbors. Furthermore,
      within the set of spread neighbors, words were more rapidly recognized when they
      had equally rather than unequally spread neighbors. The findings are explained in
      terms of activation and inhibition processes in the interactive activation
      framework.

PMID- 17225194
TI  - Homocysteine as a risk factor for cardiovascular disease: should we (still) worry
      about?
AB  - Cardiovascular disease (CVD) is the leading cause of death worldwide. CVD is
      causally related to "classical" risk factors such as elevated blood pressure,
      cholesterol, or glucose level and smoking. A causal role in the development of
      CVD is also suggested for numerous other factors, including an elevated plasma
      homocysteine concentration. Variation of homocysteinaemia is mainly due to
      genetic mutations and/or vitamin deficiency. The homocysteine concentration can
      be lowered with folate. Vitamin supplementation has thus been proposed in
      individuals with hyperhomocysteinaemia in order to reduce their CVD risk. On the
      other hand, population-based studies show little or no association between
      moderate hyperhomocysteinaemia and CVD risk. Nor has any randomised clinical
      trial clearly proven the efficacy of lowering the homocysteine concentration as a
      means of lowering the incidence of CVD. Hence at present it is inappropriate to
      recommend screening and treatment of hyperhomocysteinaemia in asymptomatic
      persons with or without other CVD risk. Until new evidence is available,
      clinicians should focus on better control of the "classical" risk factors for
      CVD.

PMID- 17225195
TI  - Atrial fibrillation: estimated excess rate of stroke due to lacking adherence to
      guidelines.
AB  - QUESTIONS UNDER STUDY: Many patients with atrial fibrillation (AF), risk factors
      for stroke and no obvious contraindications do not receive oral anticoagulation.
      Estimations of the increased rate of stroke due to neglected anticoagulation,
      particularly in an elderly, non-selected population, are unknown. METHODS:
      Consecutive patients with paroxysmal or permanent atrial fibrillation admitted to
      the medical or surgical department of our hospital for any reason were studied.
      Risk factors for stroke and contraindications for anticoagulation were recorded.
      Estimations of the increased rate of cerebrovascular events due to neglected
      anticoagulation were based on data of a large meta-analysis. Patients were
      further stratified into different age and risk groups. RESULTS: 484 patients with
      a mean age of 75 (12) years were studied, 45% were female. 237 patients had no
      oral anticoagulation at hospital discharge, despite guideline recommendations.
      Contraindications for anticoagulation were found in 85 (36%) of these patients,
      resulting in 152 patients with neglected anticoagulation (31% of all patients
      with AF). We estimated that, if all those patients would have been treated
      according to guidelines, 7.4 strokes per year could be prevented in the study
      population. The estimated rate of preventable events was 4.9%/year (7.4/152).
      CONCLUSIONS: With better adherence to guidelines for oral anticoagulation in
      patients with atrial fibrillation and risk factors for stroke, a significant
      number of strokes could be prevented.

PMID- 17225196
TI  - Can high-risk offenders be reliably identified? A follow-up study on dangerous
      offenders in Switzerland released from prison for legal reasons.
AB  - After the recent introduction of preventive detention in Germany, the Swiss
      national council has passed a similar law. In both these countries, as well as
      other nations, there is a controversial debate on post-sentence preventive
      detention of offenders who are found to be very dangerous during enforcement of
      sentence. Empirical results as to if and how far post-sentence preventive
      detention is sensible and appropriate are lacking, due to the scarcity of such
      cases and the need for systematic observation and long survey periods. In all
      cases used in the present study, a very high dangerousness was assessed during
      enforcement of sentence, but release had to be granted for legal reasons. With a
      total of nine cases (all registered from 1997 to 2005), these high-risk offenders
      represented a small and narrowly defined group, ie 2% of all violent and sex
      offenders administered by the Canton of Zurich. They also differ from the main
      population regarding socio-demographics and psychiatric and criminological
      aspects. It was possible to evaluate the progress of eight of the released
      offenders in a follow-up study. All eight offenders re-offended with grave
      violent and sex offences, seven within a year of their release, causing a total
      of twenty-four victims. The present study supports the supposition that at least
      some categories of very dangerous offenders can be reliably detected. It also
      supports the notion that systematic risk assessment during enforcement of
      sentence, using all obtainable information, can help prevent serious violent and
      sex offences. Furthermore, the results also illustrate the necessity of post
      sentence preventive detention of a small number of high-risk offenders as an
      important measure for the protection of potential victims.

PMID- 17225197
TI  - Prescribing practice in a Swiss primary and secondary acute care hospital.
AB  - QUESTIONS UNDER STUDY: Little is known about the prescribing behaviour of
      physicians in hospitals. This analysis, using data based on Computerised
      Physician Order Entry (CPOE), was performed to evaluate prescription patterns, to
      analyse possible over-prescribing of drugs and to assess the compliance with
      therapy-guidelines. METHODS: Within a 12 month period, 68,133 prescriptions in
      three departments were analysed with respect to drug class, duration of therapy,
      dosage, administration route, patient's age, patient's length of stay and number
      of prescriptions per patient. RESULTS: On average, each patient received 12
      drugs. A steady increase in the number of prescribed drugs can be seen between
      the age of 20 and 85. The median duration of intravenously administered
      antibiotics was 4.0 days, the median duration of antibiotic therapy was 9.5 days.
      DISCUSSION: On average, patients were taking 5 drugs on a regular basis on
      admission to hospital. This number was doubled during the hospital stay where
      patients were prescribed 12 drugs on average. On discharge 6 drugs were
      prescribed and thus a reasonable reduction was made. Surgical and Internal
      Medicine wards were using very similar drug classes. Concerning the use of low
      molecular-weight heparin, guidelines were widely adhered to whereas proton-pump
      inhibitors were prescribed too often and the duration of intravenous antibiotic
      therapy tended to be too long.

PMID- 17225198
TI  - A Swiss survey on teaching evidence-based medicine.
AB  - QUESTIONS UNDER STUDY: To explore the degree to which evidence-based medicine
      (EBM) is taught in postgraduate training in different clinical fields. METHODS: A
      questionnaire was mailed to all residents in Swiss hospitals in postgraduate
      medical training programs to obtain specialist titles. Response rate was 65%. In
      an Internet survey, directors of the medical training programs answered questions
      on teaching EBM. Response rate was 75%. RESULTS: Four items used to measure the
      teaching of EBM formed a reliable scale. Teaching EBM is more important in
      internal medicine than in the other clinical fields examined. The lowest values
      were obtained for general surgery. Higher values were observed in the teacher
      sample compared with the resident sample. CONCLUSIONS: In most clinical fields,
      EBM seems not to be an important part of the curriculum. Residents evaluate the
      training differently from teachers. Feedback mechanisms are essential so that
      teachers can know how their training programs are evaluated.

PMID- 17225199
TI  - [Write an article!].

PMID- 17225200
TI  - [Gene-expression profiling in schizophrenia: an overview].
AB  - BACKGROUND: In recent molecular-biological research it has become possible to
      study the activity of genes. Gene expression is characterized, among other
      things, by its variability and its dependence on the developmental phase of the
      organism, on the cell- and tissue-type, and on environmental factors. Now we have
      a technique by which the activity of the 30,000 or more genes that make up the
      human genome can be measured in one go. This technique is known as 'microarray
      screening', 'high-throughput-analysis, or gene-expression profiling'. AIM: To
      describe some of the fundamentals of the gene-expression technique and to present
      an overview of the results of gene-expression studies of brain tissue taken from
      deceased patients. METHOD: We searched PubMed for relevant articles using the
      search terms 'schizophrenia', 'micro-array' and 'gene expression'. We located 10
      articles/studies. RESULTS AND CONCLUSION: We conclude that gene-expression
      profiling has produced some evidence that several functional groups of genes are
      involved in schizophrenia (e.g. gene groups relating to synapses, metabolism,
      myelination and oligodendrocytes). Several of these genes are located on known
      chromosomal risk loci for schizophrenia. Together these findings support the
      theories that postulate that schizophrenia is caused by disturbances in synaptic
      stability and plasticity. There is some evidence that disturbances in myelination
      and fatty-acid metabolism may also play a role.

PMID- 17225202
TI  - [Remission criteria in schizophrenia].
AB  - BACKGROUND: Recent research shows that there is a considerable variation in the
      incidence and course of schizophrenia. The illness therefore can best be defined
      in terms of changeability and plasticity. AIM: An internationally accepted
      standard definition of symptomatic remission. METHOD: Two international panels of
      experts have wrestled with the problem of whether or how symptomatic remission in
      persons diagnosed with schizophrenia can be defined. A draft definition was
      published recently. RESULTS: The proposed definition is conceptually viable and
      can be incorporated easily into both clinical practice and clinical research.
      Acceptance of the remission concept can raise expectations about treatment
      outcome to a higher level than is possible when a patient is merely defined as
      being 'stable', can improve the quality of treatment documentation and facilitate
      the dialogue concerning treatment expectations. The availability of validated
      outcome measures based on remission should enhance the reporting and the
      comparability of clinical research and should facilitate the design and
      interpretation of new research into the relation between symptomatic remission
      and functional outcomes. CONCLUSION: The introduction of standard remission
      criteria can create many opportunities for clinical practice, clinical research
      and cumulative records of results; at the same time it can facilitate a dialogue
      with patients and help to clarify the diagnosis of schizophrenia.

PMID- 17225203
TI  - [An imbalance between drive and guidance. A new model for the pathogenesis of
      schizophrenia].
AB  - BACKGROUND: We still do not know how genetic and environmental factors cause
      schizophrenia. The pathogenesis of this illness is unknown. AIM: To develop a
      pathogenetic model that has greater explanatory power than the existing
      hypotheses concerning schizophrenia. METHOD: We searched the literature with the
      help of Medline (from 1966) using the search terms 'schizophrenia', 'basal
      ganglia', 'striatum' and 'cerebellum'. We also consulted recent manuals on
      schizophrenia, evolutionary psychiatry and neuroanatomy. RESULTS: The analysis
      showed that during the phylogenesis and ontogenesis of the brain two mechanisms,
      which are primarily motor-control mechanisms, are applied to the intentional
      level of functioning; one of these initiates and delivers power to intentions
      (the drive mechanism), whereas the other steers and guides intentions (the
      guidance mechanism). As a result of the repeated application of these two
      mechanisms an imbalance to the detriment of the drive mechanism in the end
      manifests itself as schizophrenia. The model clarifies the clinical and
      epidemiological findings and the course of the illness. CONCLUSION: The model
      provides a more comprehensive explanation for existing clinical and
      epidemiological data than do current alternatives. The model is compliable with
      the main prevailing views of psychiatrists on schizophrenia and it places the
      genesis of schizophrenia in an evolutionary perspective.

PMID- 17225204
TI  - [Dose reduction of conventional antipsychotics: does it reduce tardive
      dyskinesia?].
AB  - The first step in the treatment of tardive dyskinesia is to reduce the dose of
      antipsychotics. The view sometimes expressed in general practice is that,
      initially, dose reduction exacerbates tardive dyskinesia, which is an effect that
      can be explained on theoretical grounds. However, it is apparent from published
      scientific research that dose reduction of conventional antipsychotics tends to
      improve tardive dyskinesia rather than exacerbate it.

PMID- 17225205
TI  - [Reduction of prolonged QTc-interval related risks in treatment with
      neuropharmacological drugs. Recommendations for clinical practice].
AB  - A prolonged QTc-interval may cause potentially life-threatening arrhythmias.
      Almost all drugs used in psychiatric practice are able to prolong the QTc
      interval. There are some indications that clinicians are not sufficiently aware
      of the risks of QTc-interval prolongation in clinical practice. By drawing up a
      list of risk factors associated with prolonged QTc-interval and by correcting for
      these factors as far as possible, one should be able to reduce the overall risk
      of potentially lethal arrhythmias and administer more appropriate pharmacological
      treatment.

PMID- 17225206
TI  - [Cotard's syndrome. Different treatment strategies according to
      subclassification].
AB  - After performing an exploratory factor analysis, Berrios & Luque (1995)
      identified three subcategories in the Cotard's syndrome: Cotard type I, Cotard
      type II and Cotard type psychotic depression. The article, which is based on two
      case studies and an examination of the relevant literature since 1995, explores
      whether there are different treatment strategies for Cotard type I and the Cotard
      type psychotic depression. For the Cotard type psychotic depression,
      electroconvulsive therapy proves to be an effective method of treatment. For
      Cotard type I, antipsychotic therapy seems to be sufficient.

PMID- 17225209
TI  - Long-term function and manovolumetric characteristics after ileal pouch-anal
      anastomosis for ulcerative colitis.
AB  - BACKGROUND: Long-term pouch function and physiological characteristics after
      ileal pouch-anal anastomosis (IPAA) are poorly described. The aim of this study
      was to undertake a prospective investigation of long-term pouch function and
      manovolumetric characteristics. METHODS: Forty-two patients with a median follow
      up of 16 years after IPAA were included. Function was assessed using a
      questionnaire and a score was calculated ranging from 0 to 15 (15 being the
      worst). Manovolumetry was performed and pouchitis recorded. A paired analysis was
      conducted, as the results were compared with previous data for each patient.
      RESULTS: The median functional score was 3.5 (range 0-10) at 2 years and 5 (range
      1-11) at 16 years (P = 0.013). Resting anal canal pressures were higher (P <
      0.001) and squeeze pressures lower (P = 0.008) at long-term follow-up. Ileal
      pouch volumes at distension pressures of 10, 20 and 40 cm H(2)O were diminished
      at 16 years (P < 0.001, P = 0.005 and P = 0.058 respectively). The volume and
      pressure for first sensation and urge to defaecate were reduced. Increased age
      correlated positively with a poor functional score. A history of pouchitis did
      not affect functional or physiological characteristics. CONCLUSION: Ileal pouch
      function declines in the long term. The reasons are unclear, but the ageing
      process may have an impact.

PMID- 17225211
TI  - Inspired supplemental oxygen reduces markers of oxidative stress during elective
      colon surgery.

PMID- 17225210
TI  - Results at up to 20 years after ileal pouch-anal anastomosis for chronic
      ulcerative colitis.
AB  - BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is performed routinely for
      chronic ulcerative colitis. METHODS: Using data from a prospective database and
      annual standardized questionnaires, functional outcome, complications and quality
      of life (QoL) after IPAA were assessed. RESULTS: Some 1885 IPAA operations were
      performed for chronic ulcerative colitis over a 20-year period (mean follow-up 11
      years). The mean age at the time of IPAA was 34.1 years, increasing from 31.2
      years (1981-1985) to 36.3 years (1996-2000). The overall rate of pouch success at
      5, 10, 15 and 20 years was 96.3, 93.3, 92.4 and 92.1 per cent respectively. Mean
      daytime stool frequency increased from 5.7 at 1 year to 6.4 at 20 years (P <
      0.001), and also increased at night (from 1.5 to 2.0; P < 0.001). The incidence
      of frequent daytime faecal incontinence increased from 5 to 11 per cent during
      the day (P < 0.001) and from 12 to 21 per cent at night (P < 0.001). QoL remained
      unchanged and 92 per cent remained in the same employment. Seventy-six patients
      were eventually diagnosed with indeterminate colitis and 47 with Crohn's disease.
      CONCLUSION: IPAA is a reliable surgical procedure for patients requiring
      proctocolectomy for chronic ulcerative colitis and indeterminate colitis. The
      clinical and functional outcomes are excellent and stable for 20 years after
      operation.

PMID- 17225212
TI  - The interpretation of exposure effect estimates in chronic air pollution studies.
AB  - In this article we consider the interpretation of regression parameters used to
      represent 'chronic' or 'long-term' air pollution exposure effects. Although
      scientific interest typically lies in understanding such effects at the level of
      the individual, studies have generally employed a semi-ecological design;
      outcomes and confounder information are collected on individuals while exposure
      is only available at the aggregate-or group-level. A precise interpretation of
      results from a semi-ecological design must take into account the aggregated
      nature, both spatial and temporal, of the exposure measure. The most common
      analysis approach for assessing chronic exposure effects has been within the Cox
      proportional hazards model framework; specific analyses are tailored to
      accommodate the shortcomings of the available exposure information. We revisit
      the underlying assumptions of the Cox model and discuss the implications of two
      common aspects of chronic effects studies: time-dependent exposures and time
      varying effects. Focusing on the consequences of temporal aggregation of
      exposure, we show that an estimate obtained from a time-aggregated semi
      ecological design can correspond to very different underlying time-varying
      exposure and risk scenarios. Further, distinguishing which of these is correct is
      not possible from the semi-ecological data alone. Our goal is to highlight some
      statistical issues faced by existing studies of chronic air pollution effects,
      and aid in the development and planning of future studies.

PMID- 17225213
TI  - Computer-aided diagnosis with potential application to rapid detection of disease
      outbreaks.
AB  - Our objectives are to quickly interpret symptoms of emergency patients to
      identify likely syndromes and to improve population-wide disease outbreak
      detection. We constructed a database of 248 syndromes, each syndrome having an
      estimated probability of producing any of 85 symptoms, with some two-way, three
      way, and five-way probabilities reflecting correlations among symptoms. Using
      these multi-way probabilities in conjunction with an iterative proportional
      fitting algorithm allows estimation of full conditional probabilities. Combining
      these conditional probabilities with misdiagnosis error rates and incidence rates
      via Bayes theorem, the probability of each syndrome is estimated. We tested a
      prototype of computer-aided differential diagnosis (CADDY) on simulated data and
      on more than 100 real cases, including West Nile Virus, Q fever, SARS, anthrax,
      plague, tularaemia and toxic shock cases. We conclude that: (1) it is important
      to determine whether the unrecorded positive status of a symptom means that the
      status is negative or that the status is unknown; (2) inclusion of misdiagnosis
      error rates produces more realistic results; (3) the naive Bayes classifier,
      which assumes all symptoms behave independently, is slightly outperformed by
      CADDY, which includes available multi-symptom information on correlations; as
      more information regarding symptom correlations becomes available, the advantage
      of CADDY over the naive Bayes classifier should increase; (4) overlooking low
      probability, high-consequence events is less likely if the standard output
      summary is augmented with a list of rare syndromes that are consistent with
      observed symptoms, and (5) accumulating patient-level probabilities across a
      larger population can aid in biosurveillance for disease outbreaks.

PMID- 17225214
TI  - Designer self-assembling peptide materials.
AB  - Understanding of macromolecular materials at the molecular level is becoming
      increasingly important for a new generation of nanomaterials for
      nanobiotechnology and other disciplines, namely, the design, synthesis, and
      fabrication of nanodevices at the molecular scale from bottom up. Basic
      engineering principles for microfabrication can be learned through fully grasping
      the molecular self-assembly and programmed assembly phenomena. Self- and
      programmed-assembly phenomena are ubiquitous in nature. Two key elements in
      molecular macrobiological material productions are chemical complementarity and
      structural compatibility, both of which require weak and non-covalent
      interactions that bring building blocks together during self-assembly.
      Significant advances have been made during the 1990s at the interface of
      materials chemistry and biology. They include the design of helical ribbons,
      peptide nanofiber scaffolds for three-dimensional cell cultures and tissue
      engineering, peptide surfactants for solubilizing and stabilizing diverse types
      of membrane proteins and their complexes, and molecular ink peptides for
      arbitrary printing and coating surfaces as well as coiled-coil helical peptides
      for multi-length scale fractal structures. These designer self-assembling
      peptides have far reaching implications in a broad spectrum of applications in
      biology, medicine, nanobiotechnology, and nanobiomedical technology, some of
      which are beyond our current imaginations. [image: see text]

PMID- 17225216
TI  - Self-assembly of semifluorinated minidendrons attached to electron-acceptor
      groups into pyramidal columns.
AB  - The synthesis and self-assembly of twelve semifluorinated first-generation
      dendrons or minidendrons attached to electron-acceptor (n-type) groups generated
      from various combinations of eight acceptors and three dendrons are reported.
      Dendrons attached to small electron-acceptor molecules mediate their self
      assembly into pi-stacks located in the center of a supramolecular helical
      pyramidal column with the long axis of the acceptor perpendicular to the long
      axis of the column. Dendrons attached to large electron-acceptor molecules, such
      as perylene bisimide, mediate the assembly of their acceptors in an unprecedented
      arrangement of pi-stacks that have the long axis of the acceptors parallel to the
      long axis of the supramolecular pyramidal column. All supramolecular columns self
      organize into various periodic columnar arrays that exhibit liquid-crystalline
      phases, crystalline phases, or a liquid-crystalline phase with enhanced
      intracolumnar order. The present study demonstrates the simplicity and the
      versatility of the concept of assembly of n-type electroactive groups mediated by
      semifluorinated dendrons and assesses the scope and limitations of this
      supramolecular strategy.

PMID- 17225217
TI  - First-principles molecular dynamics evaluation of thermal effects on the NMR
      (1)J(Li,C) spin-spin coupling.
AB  - Car-Parrinello (CP) molecular dynamics were applied to sample conformations of
      various models of organolithium aggregates which are chosen to estimate
      (1)J(Li,C) NMR coupling constants. The results show that the deviations from the
      values computed using static (optimized) geometries are small provided no large
      amplitude motions occur within the timescale of the simulations. In the case of
      the vinyllithium dimer, for which rotation of the vinyl chain is observed, this
      approach allows analysis of the various contributions to the experimentally
      measured constants. For the trisolvated methyllithium monomer, partial
      decoordination of solvating dimethyl ether is observed and results in a
      significant shift of (1)J(Li,C). All these results highlight that a varied
      physicochemical machinery is hidden behind general empirical formulas, such as
      the Bauer-Winchester-Schleyer rule used experimentally.

PMID- 17225219
TI  - Water-soluble self-assembled butadiyne-bridged bisporphyrin: a potential two
      photon-absorbing photosensitizer for photodynamic therapy.
AB  - We have synthesized a novel, two-photon-absorbing photosensitizer for two-photon
      absorption photodynamic therapy (2PA-PDT). The molecule is a butadiyne-bridged
      porphyrin dimer terminated with two water-soluble porphyrin monomers connected
      through Zn-imidazolyl self-assembly and covalently linked through olefin
      metathesis. It has an effective two-photon-absorption (2PA) cross-section value,
      sigma((2)), of 33 000+/-4600 GM with 5-ns pulses at 890 nm measured by using the
      open-aperture Z-scan technique. The compound was found to generate singlet
      oxygen, cytotoxic for tumor cells in photodynamic therapy (PDT), under 2PA
      conditions by conducting photobleaching experiments with anthracene-9,10
      dipropionic acid sodium salt (ADPA).

PMID- 17225218
TI  - The supramolecular helical architecture of 8-oxoinosine and 8-oxoguanosine
      derivatives.
AB  - The 8-oxoguanosine derivative 1 and the 8-oxoinosine derivative 2 b, with
      appropriate substituents on their ribose moieties, form hexagonal lyotropic
      mesophases in hydrocarbon solvents. Small-angle X-ray scattering analysis of a
      film of 1 and of the mesophase of 2 b, and NMR and CD spectra of isotropic
      solutions of 2 b, indicate that in both cases the supramolecular structures
      adopted are continuous helices formed by a hydrogen-bond network between the
      heterocyclic bases. Notably, while derivative 2 b, which bears large substituents
      on its ribose moiety, undergoes self-assembly and mesophase formation, oxoinosine
      2 a, with only decanoyl groups on its ribose moiety, does not. This may be
      ascribed to the reduced amphiphilic properties of the latter and the absence of
      aromatic groups.

PMID- 17225220
TI  - The first pure LambdaHT rotamer of a complex with a cis-[metal(nucleotide)2]
      unit: a cis-[Pt(amine)2(nucleotide)2] LambdaHT rotamer with unique molecular
      structural features.
AB  - cis-[PtA2(nucleotide)2] complexes (A2 stands for two amines or a diamine) have
      been extensively investigated as model compounds for key cisplatin-DNA adducts.
      All cis-[metal(nucleotide/nucleoside)2] complexes with guanine and related
      purines characterized in the solid state thus far have the DeltaHT conformation
      (head-to-tail orientation of the two bases and right-handed chirality). In sharp
      contrast, the LambdaHT conformation (left-handed chirality) dominates in acidic
      and neutral aqueous solutions of cis-[PtA2(5'-GMP)2] complexes. Molecular models
      and solution experiments indicate that the LambdaHT conformer is stabilized by 5'
      phosphate/N1H hydrogen-bond interactions between cis nucleotides with the normal
      anti conformation. However, this evidence, while compelling, is indirect. At
      last, conditions have been defined to allow crystallization of this elusive
      conformer. The structure obtained reveals three unique features not present in
      all other cis-[PtA2(nucleotide)2] solid-state structures: a LambdaHT
      conformation, very strong hydrogen-bond interactions between the phosphate and
      N1H of cis nucleotides, and a very small dihedral angle between the planes of the
      two guanines lying nearly perpendicular to the coordination plane. These new
      results indicate that, because there are no local base-base repulsions precluding
      the LambdaHT conformer, global forces rather than local interactions account for
      the predominance of the DeltaHT conformer over the LambdaHT conformer in the
      solid state and in both inter- and intrastrand HT crosslinks of oligonucleotides
      and DNA.

PMID- 17225221
TI  - High enantioselectivity is induced by a single monodentate phosphoramidite ligand
      in iridium-catalyzed asymmetric hydrogenation.

PMID- 17225222
TI  - Aligned carbon nanotubes in the supramolecular order of discotic liquid crystals.

PMID- 17225223
TI  - Towards a 32-electron principle: Pu@Pb12 and related systems.

PMID- 17225224
TI  - Photopatterned arrays of fluorescent organic nanoparticles.

PMID- 17225225
TI  - Single-crystal organic microtubes with a rectangular cross section.

PMID- 17225226
TI  - The azaallylic anion as a synthon for pd-catalyzed synthesis of heterocycles:
      domino two- and three-component synthesis of indoles.

PMID- 17225227
TI  - Total synthesis of (+)-aquaticol by biomimetic phenol dearomatization: double
      diastereofacial differentiation in the Diels-Alder dimerization of orthoquinols
      with a C2-symmetric transition state.

PMID- 17225228
TI  - The use of quantum molecular calculations to guide a genetic algorithm: a way to
      search for new chemistry.
AB  - The process of gene-based molecular evolution has been simulated in silico by
      using massively parallel density functional theory quantum calculations, coupled
      with a genetic algorithm, to test for fitness with respect to a target chemical
      reaction in populations of genetically encoded molecules. The goal of this study
      was the identification of transition-metal complexes capable of mediating a known
      reaction, namely the cleavage of N(2) to give the metal nitride. Each complex
      within the search space was uniquely specified by a nanogene consisting of an
      eight-digit number. Propagation of an individual nanogene into successive
      generations was determined by the fitness of its phenotypic molecule to perform
      the target reaction and new generations were created by recombination and
      mutation of surviving nanogenes. In its simplest implementation, the quantum
      directed genetic algorithm (QDGA) quickly located a local minimum on the
      evolutionary fitness hypersurface, but proved incapable of progressing towards
      the global minimum. A strategy for progressing beyond local minima consistent
      with the Darwinian paradigm by the use of environmental variations coupled with
      mass extinctions was therefore developed. This allowed for the identification of
      nitriding complexes that are very closely related to known examples from the
      chemical literature. Examples of mutations that appear to be beneficial at the
      genetic level but prove to be harmful at the phenotypic level are described. As
      well as revealing fundamental aspects of molecular evolution, QDGA appears to be
      a powerful tool for the identification of lead compounds capable of carrying out
      a target chemical reaction.

PMID- 17225229
TI  - Analysis of intramolecular dynamic processes in enantiomeric diaryl atropisomers
      and related derivatives by 2H NMR spectroscopy in polypeptide liquid crystals.
AB  - We demonstrate the analytical potential of 2H-{1H} NMR spectroscopy in weakly
      ordering, chiral lyotropic liquid crystals made of poly(gamma-benzyl-L-glutamate)
      (PBLG) dissolved in chloroform or dichloromethane for investigating the
      intramolecular dynamic processes of four deuterated diaryls (derivatives of 1-(4'
      methylphenyl)naphthalene). When the rotation of the aryl groups about the sp(2)-
      sp(2) bond is sufficiently slow relative to the NMR timescale, the method allows
      the spectral discrimination of enantiomeric atropisomers or enantiotopic
      directions in the prochiral derivatives. The effect of the position of
      substituents on the phenyl group on the conformational dynamics of these
      compounds has been examined as well as the nature of the organic co-solvent. When
      coalescence phenomena are observed, simulation of the experimental 2H-{1H}
      lineshapes using a formalism tailored for two deuterons undergoing mutual
      exchange allows the rate constants and the activation parameters for the internal
      rotation processes to be calculated. Experimental values of DeltaH(not equal)
      have been compared with data evaluated by molecular modelling calculations and
      the activation parameters are discussed for the various compounds. It is shown
      that these polypeptide mesophases have no significant impact on the
      interconversion dynamics of these compounds. In contrast with the nematic
      thermotropic phases, Haller's equation cannot be used to predict the evolution of
      the quadrupolar splittings (Deltanu(Q) values), and hence the order parameters,
      versus T in the PBLG mesophases. For these particular lyotropic systems, it is
      shown that an exponential function of the form Deltanu(Q)[Hz]=C x exp (-E/RT[K])
      provides excellent agreement between the experimental and expected Deltanu(Q)
      values. Analysis of the results reported in this work suggests that orientation
      and chiral discrimination phenomena in these lyotropic solvents could be treated
      separately because they would involve different interaction mechanisms.

PMID- 17225230
TI  - Tuning the polarization along linear polyaromatic strands for rationally inducing
      mesomorphism in lanthanide nitrate complexes.
AB  - The opposite orientation of the ester spacers in the rodlike ligands L 4C12
      (benzimidazole-OOC-phenyl) and L 5C12 (benzimidazole-COO-phenyl) drastically
      changes the electronic structure of the aromatic systems, without affecting their
      meridional tricoordination to trivalent lanthanides, Ln(III), and their
      thermotropic liquid crystalline (i.e., mesomorphic) behaviors. However, the rich
      mesomorphism exhibited by the complexes [Ln(L 4C12)(NO3)3] (Ln=La-Lu) vanishes in
      [Ln(L 5C12)(NO3)3], despite superimposable molecular structures and comparable
      photophysical properties. Density functional theory (DFT) and time-dependant DFT
      calculations performed in the gas phase show that the inversion of the ester
      spacers has considerable effects on the electronic structure and polarization of
      the aromatic groups along the strands, which control residual intermolecular
      interactions responsible for the formation of thermotropic liquid-crystalline
      phases. As a rule of thumb, an alternation of electron-poor and electron-rich
      aromatic rings favors intermolecular interactions between the rigid cores and
      consequently mesomorphism, a situation encountered for L 4C12, L 5C12, [Ln(L
      4C12)(NO3)3], but not for [Ln(L 5C12)(NO3)3]. The intercalation of an additional
      electron-rich diphenol ring on going from [Ln(L 5C12)(NO3)3] to [Ln(L
      6C12)(NO3)3] restores mesomorphism despite an unfavorable orientation of the
      ester spacers, in agreement with our simple predictive model.

PMID- 17225231
TI  - Synthesis and structures of cross-conjugated bis-dehydroannulenes with a Y
      enediyne motif and different pi topologies.
AB  - A synthesis of cross-conjugated bis-dehydroannulenes with different topologies of
      the pi electrons by Cu(II)-mediated oxidative coupling of the corresponding
      terminal acetylenic precursors is reported. In general, of the two possible modes
      of cyclization, which would yield either a [13]annulene or an [18]annulene, the
      precursors yielded exclusively the bis-dehydro[13]annulenes. However, one example
      of the formation of a bis-dehydro[18]annulene is also reported. The mode of
      cyclization to form either the [13]annulene or the [18]annulene is explained on
      the basis of the conformational preference of the core unit bearing the Y
      enediyne moieties. The structures of the two types of bis-annulenes have been
      unequivocally established by means of single-crystal X-ray crystallographic
      analysis.

PMID- 17225233
TI  - Bond orders and atomic properties of the highly deformed halogenated fullerenes
      C60F18 and C60Cl30 derived from their charge densities.
AB  - The experimental charge densities of the halogenated C(60) fullerenes C(60)F(18)
      and C(60)Cl(30) were determined from high-resolution X-ray data sets measured
      with conventional Mo(Kalpha) radiation at 20 K for C(60)Cl(30) and with
      synchrotron radiation at 92 K for the fluorine compound. Bond topological and
      atomic properties were analyzed by using Bader's AIM theory. For the different C-
      C bonds, which vary in lengths between 1.35 and 1.70 A bond orders n between n=2
      and significantly below n=1 were calculated from the bond topological properties
      at the bond critical points (BCP's). The low bond orders are seen for 5/6 bonds
      with each contributing carbon carrying a halogen atom. By integration over
      Bader's zero flux basins in the electron density gradient vector field atomic
      properties were also obtained. In contrast to free C(60), in which all carbon
      atoms have a uniform volume of 11 A(3) and zero charge, atomic volumes vary
      roughly between 5 and 10 A(3) in the halogenated compounds. Almost zero atomic
      charges are also found in the Cl derivative but a charge separation up to +/-0.8
      e exists between C and F in C(60)F(18) due to the higher fluorine
      electronegativity, which is also seen in the electrostatic potential for which
      the electronegativity difference between carbon and fluorine, and the addition to
      one hemisphere of the fullerene cage leads to a strong potential gradient along
      the C(60)F(18) molecule. From the summation over all atomic volumes it follows
      that the halogen addition does not only lead to a dramatic distortion of the
      C(60) cage but also to a significant shrinkage of its volume.

PMID- 17225232
TI  - One-pot solid-phase glycoblotting and probing by transoximization for high
      throughput glycomics and glycoproteomics.
AB  - The development of rapid and efficient methods for high-throughput protein
      glycomics is of growing importance because the glycoform-focused reverse
      proteomics/genomics strategy will greatly contribute to the discovery of novel
      biomarkers closely related to cellular development, differentiation, growth, and
      aging as well as a variety of diseases such as cancers and viral infection.
      Recently, we communicated that rapid and efficient purification of carbohydrates
      can be achieved by employing sugar-specific chemical ligation with aminooxy
      functionalized polymers, which we termed "glycoblotting" (see S.-I. Nishimura et
      al., Angew. Chem. 2005, 117, 93-98; Angew. Chem. Int. Ed. 2005, 44, 91-96). The
      chemoselective blotting of oligosaccharides present in crude biological materials
      onto synthetic polymers relies on the unique oxime-bond formation between
      aminooxy group displayed on the supporting materials and aldehyde/ketone group at
      the reducing terminal of all oligosaccharides, thus enabling highly selective and
      rapid oligosaccharide purification. Aiming to improve the detection sensitivity
      of the released oligosaccharides, we introduce here a novel strategy for one-pot
      solid-phase glycoblotting and probing by transoximization. We found that
      oligosaccharides captured by the polymer supports via the oxime bond can be
      released in the presence of excess O-substituted aminooxy derivatives in a weakly
      acidic condition. The released oligosaccharides could be recovered as newly
      formed oxime derivatives of the O-substituted aminooxy compound added, thus
      demonstrating the simultaneous releasing and probing. In addition, we synthesized
      a novel aminooxy-functionalized monomer, N-[2-[2-(2-tert
      butoxycarbonylaminooxyacetylamino-ethoxy)ethoxy]ethyl]-2-methacrylamide, which
      allows for the large-scale preparation of a versatile polymer characterized by
      its high stability, high blotting capacity, and easy use. The one-pot protocol
      allowed to profile 23 kinds of N-glycan chains of human serum glycoproteins. This
      concept was further applied for the glycopeptides analysis in a crude mixture
      followed by galactose oxidase treatment to generate free aldehyde group at the
      non-reducing terminal of oligosaccharide moiety of glycopeptides. Our technique
      may be implemented in existing biochemistry and molecular diagnostics
      laboratories because enriched oligosaccharides and glycopeptides by solid-phase
      transoximization with high-sensitive labeling reagents are widely applicable in a
      variety of common analytical methods using two-dimensional HPLC, LC/MS, and
      capillary electrophoresis as well as modern mass spectrometry.

PMID- 17225234
TI  - Total synthesis, molecular editing and evaluation of a tripyrrolic natural
      product: the case of "butylcycloheptylprodigiosin".
AB  - Conflicting reports are found in the literature on whether the ortho-pyrrolophane
      derivative 6, which has been named "butylcycloheptylprodigiosin" even though it
      is a cyclononane derivative, is a natural product or merely a mis-assigned
      structure. This dispute has now been resolved by an unambiguous total synthesis
      of this complex alkaloid which confirms the initial structure assignment. The
      chosen approach is largely catalysis-based, featuring the first application of a
      "Narasaka-Heck" reaction in natural product chemistry. This palladium-catalyzed
      transformation allows the unsaturated oxime ester 26 to be converted into the
      bicyclic dihydropyrrole 27. Other notable reactions of the reported approach to 6
      are a regioselective Tsuji-Trost reaction of the doubly allylic acetate 21 with
      methyl acetoacetate, a base-induced aromatization of 27 to the corresponding
      pyrrole 28, a chemoselective oxidation of the benzylic methyl group in 33 with
      cerium ammonium nitrate in a biphasic reaction medium that does not affect the
      labile pyrrole nucleus, and a Suzuki cross-coupling for the completion of the
      heterocyclic domain. Diversification in the latter step leads to a set of
      analogues that differ from the natural product in the terminal (hetero)arene
      ring. This structural modification results in complete loss of the very
      pronounced ability of the parent compound 6 to induce oxidative cleavage in
      double stranded DNA in the presence of Cu(II). Several cyclononane-, cyclononene-
      and cyclononadiene derivatives prepared en route to 6 have been characterized by
      crystal structure analysis, allowing the conformational behavior of nine-membered
      carbocycles to be studied.

PMID- 17225235
TI  - Insulated molecular wires.
AB  - An astonishing assortment of structures have been described as "insulated
      molecular wires" (IMWs), thus illustrating the diversity of approaches to
      molecular-scale insulation. These systems demonstrate the scope of encapsulation
      in the molecular engineering of optoelectronic materials and organic
      semiconductors. This Review surveys the synthesis and structural characterization
      of IMWs, and highlights emerging structure-property relationships to determine
      how insulation can enhance the behavior of a molecular wire. We focus mainly on
      three IMW architectures: polyrotaxanes, polymer-wrapped pi systems, and
      dendronized polymers, and compare the properties of these systems with those of
      conjugated polymers threaded through mesoporous frameworks and zeolites.
      Encapsulation of molecular wires can enhance properties as diverse as
      luminescence, electrical transport, and chemical stability, which points to
      applications in electroluminescent displays, sensors, and the photochemical
      generation of hydrogen.

PMID- 17225236
TI  - Asymmetric organocatalytic domino reactions.
AB  - The current status of organic synthesis is hampered by costly protecting-group
      strategies and lengthy purification procedures after each synthetic step. To
      circumvent these problems, the synthetic potential of multicomponent domino
      reactions has been utilized for the efficient and stereoselective construction of
      complex molecules from simple precursors in a single process. In particular,
      domino reactions mediated by organocatalysts are in a way biomimetic, as this
      principle is used very efficiently in the biosynthesis of complex natural
      products starting from simple precursors. In this Minireview, we discuss the
      current development of this fast-growing field.

PMID- 17225237
TI  - Reaching the maximum multiplicity of the covalent chemical bond.

PMID- 17225238
TI  - Supramolecular liquid crystals based on cyclo[8]pyrrole.

PMID- 17225239
TI  - Time use and costs of institutionalised elderly persons with or without dementia:
      results from the Nordanstig cohort in the Kungsholmen Project--a population based
      study in Sweden.
AB  - BACKGROUND: The aging of the population has become a worldwide phenomenon. This
      leads to increased demand for services and with limited resources it is important
      to find a way to estimate how resources can be match to those with greatest need.
      AIMS: To analyse time use and costs in institutional care in relation to
      different levels of cognitive and functional capacity for elderly persons.
      METHODS: The population consisted of all institutionalised inhabitants, 75 +
      years, living in a rural community (n = 176). They were clinically examined by
      physicians and interviewed by nurses. Staff and informal care-giving time was
      examined with the RUD (Resource Utilization in Dementia) instrument. RESULTS:
      Tobit regression analyses showed that having dementia increased the amount of ADL
      care time with 0.9 h when compared to those not having dementia, whereas each
      loss of an ADL function (0-6) added 0.6 h of ADL care time. Analysing the total
      care time use, the presence of dementia added more than 9 h, while each loss of
      one ADL function added 2.9 h. There were some informal care contributions,
      however with no correlation to severity in dependency. The estimated cost for
      institutional care increased with more than 85% for people being dependent in 5-6
      ADL activities compared to persons with no functional dependency, and with 30%
      for persons with dementia compared to the non-demented. CONCLUSION: There is a
      variation in time use in institutional settings due to differences in ADL
      dependency but also whether dementia is present or not. This variation has
      implications for costs of institutional care.

PMID- 17225247
TI  - Meeting report: Breaking barriers in microscopy.

PMID- 17225249
TI  - Whole genome genotyping technologies on the BeadArray platform.
AB  - The ability to simultaneously genotype hundreds of thousands of single-nucleotide
      polymorphisms (SNPs) in a single assay has recently become feasible due to
      innovative combinations of assay and array platform multiplexing. In this review,
      we describe the development of the Infinium whole genome genotyping technology
      and the BeadArray platform. We discuss the automated use and performance of a
      series of genotyping BeadChips, including data quality, technology scalability,
      and flexibility in designing array content. We describe high-density tag SNP
      based Bead-Chips and various multi-sample BeadChip configurations with their
      respective applications. These technologies are enabling large-scale whole genome
      association studies that have the potential to revolutionize our ability to
      detect common genetic variants with a significant role in identifying disease
      associated loci, proteins, biomarkers, and pharmacogenomic responses.

PMID- 17225250
TI  - Gap junctional intercellular communication capacity by gap-FRAP technique: a
      comparative study.
AB  - Gap junctions play an important role in vital functions, including the regulation
      of cell growth and cell differentiation. Connexins 43 (Cx43) are the most widely
      expressed gap junction proteins. Cellular localization of phosphorylated Cx43 has
      been implicated in the capacity of gap junctional intercellular communication
      (GJIC). To follow the functionality of GJIC of different cell types, in monolayer
      cultures, characterized by different patterns of phosphorylated Cx43, we used a
      fluorescence recovery after photobleaching (FRAP) technique, and compared two
      tracers, 5(6)-carboxyfluorescein diacetate (CFDA) and calcein acetoxymethylester
      (AM). The GJIC capacity was quantified by estimating fluorescence redistribution
      parameters. The functionality of GJIC was in relation with the staining
      localization of phosphorylated Cx43 to the cell-cell contact areas, corresponding
      to gap junctions between contacting cells. GJIC involvement in fluorescence
      restitution after photobleaching was checked by a gap junction channel inhibition
      assay. We demonstrated that the choice of the dye did not significantly influence
      the fluorescence recovery percentages despite a cell line-dependent CFDA release,
      whereas it had an important impact on fluorescence kinetic profiles. This study
      reinforces the interest of the gap-FRAP approach to quantify modifications in the
      functionality of gap junctions and, above all, argues about the limits of CFDA
      for 3-D future approaches.

PMID- 17225251
TI  - Identification of intracellular targets of small molecular weight chemical
      compounds using affinity chromatography.
AB  - Efforts to characterize small molecular weight chemical inhibitors of
      pharmacological interest tend to identify molecules with high efficiency and
      selectivity, to meet the two criteria required for the clinical development of a
      drug: efficacy and harmlessness. Drug candidates are expected to inhibit
      efficiently the target they have been optimized against (for example, a
      particular type of protein kinase). These hits are also designed to not interfere
      (or as little as possible) with the activity of other cellular enzymes/proteins
      to reduce undesired side effects. Here we discuss the use of immobilized drugs as
      affinity chromatography matrices to purify and identify their bona fide
      intracellular targets. This method not only allows the systematic investigation
      of the selectivity of pharmacological compounds but also the anticipation of
      their putative adverse effects.

PMID- 17225253
TI  - Method for generation of human hyperdiversified antibody fragment library.
AB  - The selection of antibody fragments from libraries using in vitro screening
      technologies has proven to be a very good alternative to the classical hybridoma
      technology, and has overcome the laborious process of antibody humanization.
      However, the complexity of the library is critical in the probability of being
      able to directly isolate a high affinity antibody specific to a target. We report
      a method to make hyperdiversified antibody fragment libraries, based on human
      immunoglobulin variable genes mimicking the somatic hypermutation process. This
      mutagenesis technology, MutaGen, was used for the first time on the entire
      variable domain (frameworks and CDRs) of large repertoires of human variable
      antibody domains. Our MutaGen process uses low-fidelity human polymerases, known
      as mutases, suggested to be involved in the somatic hypermutation process of
      immunoglobulin genes. Depending on the mutases used, we generated complementary
      mutation patterns with randomly distributed mutations. The libraries were
      generated with an average of 1.8 mutations per 100 amino acids. The
      hyperdiversified antibody fragment libraries constructed with our process should
      enable the selection of antibody fragments specific to virtually any target.

PMID- 17225258
TI  - Editorial: Why methods matter.

PMID- 17225257
TI  - Rabies virus glycoprotein expression in Drosophila S2 cells. I. Functional
      recombinant protein in stable co-transfected cell line.
AB  - Recombinant rabies virus glycoprotein (rRVGP) was expressed in Drosophila
      melanogaster Schneider 2 (S2) cells. The cDNA encoding the entire RVGP gene was
      cloned in an expression plasmid under the control of the constitutive actin
      promoter (Ac), which was co-transfected into S2 cells together with a hygromycin
      selection plasmid. Selected S2 cell populations (S2AcRVGP) had a decreased
      ability to grow and consume substrates, when compared to the non-transfected
      cells (S2). They were shown, by PCR, to express the RVGP gene and mRNA and, by
      immunoblotting, to synthesize the rRVGP in its expected molecular mass of 65 kDa.
      ELISA kinetic studies showed the rRVGP expression in cell lysates and
      supernatants attaining concentrations of 300 microg/L. By flow cytometry
      analysis, about 30% of the cells in the co-transfected populations were shown to
      express the rRVGP. Cell populations selected by limiting dilution expressed
      higher rRVGP yields. Mice immunized with rRVGP were shown to synthesize
      antibodies against rabies virus and be protected against experimental infection
      with rabies virus. The data presented here show that S2 cells can be suitable
      hosts for the rRVGP expression, allowing its synthesis in a high degree of
      physical and biological integrity.

PMID- 17225260
TI  - Changes in cancer worry associated with participation in ovarian cancer
      screening.
AB  - While ovarian cancer is rare and screening is not recommended for most women, it
      is being studied as a way to reduce ovarian cancer mortality. As effective
      strategies for screening emerge it will be important to understand the quality of
      life (QOL) effects of participation in ovarian cancer screening. In this study,
      we examined the effects of participation in an ovarian cancer screening program
      on worry about cancer risk and QOL. A randomized controlled clinical trial (n =
      592) was conducted. Women without a family history suggestive of a BRCA1/2
      mutation were randomly assigned to screening and risk counseling, separately and
      in combination. Results were compared to women randomized to usual care alone.
      Levels of cancer worry fell for all study groups and QOL was unaffected; no
      statistically significant differences were found between groups. Increased levels
      of worry about ovarian cancer at 2-year follow-up were found among participants
      in screening receiving abnormal test results. For those who receive abnormal
      results, screening may have long-term effects and increase worry about cancer
      risk. Further research will be required to examine the possibility that screening
      reduces worry when women receive only normal, presumably reassuring, results.

PMID- 17225262
TI  - Antibiotic resistance. The facts behind the news.

PMID- 17225261
TI  - New risks with newer rheumatoid arthritis drugs.

PMID- 17225263
TI  - I hear there's a new vaccine to prevent whooping cough. Is this something I
      should be getting?

PMID- 17225264
TI  - I need to take a nonsteroidal anti-inflammatory drug every day to control my
      arthritis. How can I decrease my chances of developing stomach troubles?

PMID- 17225265
TI  - New guidelines for atrial fibrillation focus on stroke risk.

PMID- 17225267
TI  - Why pauses in breathing during sleep should be a wake-up call.

PMID- 17225266
TI  - To guard your heart, protect your kidneys.

PMID- 17225268
TI  - The truth about statins. Should you be concerned about harm to your liver?

PMID- 17225269
TI  - My father had several heart attacks and strokes. I know I am at risk because I
      started menopause 10 years ago, but is my risk higher than normal due to my
      family history?

PMID- 17225270
TI  - I think I should take folic acid supplements to lower my risk of heart disease. A
      friend told me not to bother. Who's right?

PMID- 17225271
TI  - Does vitamin E help prevent heart disease or heart attack?

PMID- 17225272
TI  - Tide of opinion about fish oil supplements is shifting.

PMID- 17225273
TI  - I was diagnosed with a tumor in my heart called an atrial myxoma. I hadn't
      realized that tumors occurred in the heart. How common are they?

PMID- 17225274
TI  - I heart that angioplasty with stenting doesn't save lives, and also that it does.
      This should be an easy question. Which is it?

PMID- 17225275
TI  - Infection fighters. When germs travel.

PMID- 17225276
TI  - Infection fighters. Many questions, no answers.

PMID- 17225277
TI  - Addictions. Drug twists brain and body.

PMID- 17225278
TI  - Anti-HIV agents. Kaletra and Meltrex update.

PMID- 17225279
TI  - Anti-HIV agents. Dueling nukes: AZT + 3TC vs. tenofovir + FTC.

PMID- 17225280
TI  - Anti-HIV agents. T-20 shows long-term effectiveness and safety.

PMID- 17225281
TI  - Vaccines. Study finds Remune reduces risk of virologic failure.

PMID- 17225282
TI  - Complications & side effects. Nukes and fat wasting.

PMID- 17225283
TI  - Complications & side effects. German researchers study breath test for uncovering
      mitochondrial damage.

PMID- 17225284
TI  - MODS assay for the diagnosis of TB.

PMID- 17225285
TI  - Refining prognosis in non-small-cell lung cancer.

PMID- 17225286
TI  - Case 31-2006: a girl with severe obesity.

PMID- 17225287
TI  - Refining prognosis in non-small-cell lung cancer.

PMID- 17225288
TI  - Survivors of childhood cancer.

PMID- 17225289
TI  - Survivors of childhood cancer.

PMID- 17225290
TI  - Survivors of childhood cancer.

PMID- 17225291
TI  - Case 31-2006: a girl with severe obesity.

PMID- 17225292
TI  - City bus driving and low back pain: a study of the exposures to posture demands,
      manual materials handling and whole-body vibration.
AB  - A cross-sectional study was conducted to investigate worker exposure to posture
      demands, manual materials handling (MMH) and whole body vibration as risks for
      low back pain (LBP). Using validated questionnaire, information about driving
      experience, driving (sitting) posture MMH, and health history was obtained from
      80 city bus drivers. Twelve drivers were observed during their service route
      driving (at least one complete round trip) and vibration measurements were
      obtained at the seat and according to the recommendations of ISO 2631 (1997), for
      three models of bus (a mini-bus, a single-decker bus, a double-decker bus). The
      results showed that city bus drivers spend about 60% of the daily work time
      actually driving, often with the torso straight or unsupported, perform
      occasional and light MMH, and experience discomforting shock/jerking vibration
      events. Transient and mild LBP (not likely to interfere with work or customary
      levels of activity) was found to be prevalent among the drivers and a need for
      ergonomic evaluation of the drivers' seat was suggested.

PMID- 17225294
TI  - PTSD and Vietnam Veterans.

PMID- 17225293
TI  - The comparative efficacy and safety of biologics for the treatment of rheumatoid
      arthritis: a systematic review and metaanalysis.
AB  - OBJECTIVE: Biologics are an important therapeutic option for treating patients
      with rheumatoid arthritis (RA). However, they are associated with rare but severe
      adverse events such as serious infections, lymphoma, or chronic heart failure. In
      addition, dosing regimens and routes of administration differ substantially among
      biologics. In a systematic review, we assessed the comparative efficacy and
      safety of biologic agents for RA. METHODS: We searched electronic databases up to
      May 2006. We limited evidence to controlled trials for efficacy but included
      observational evidence for safety. Outcomes of interest were clinical response,
      radiographic progression, and quality of life. Given the paucity of head-to-head
      evidence, we conducted adjusted, indirect comparisons of placebo-controlled
      trials. RESULTS: Twenty-six controlled trials provided efficacy data; 18
      additional studies assessed safety. The only evidence directly comparing 2
      biologic agents was a nonrandomized, open-label trial that found no differences
      in effectiveness and safety between etanercept and infliximab. Adjusted indirect
      comparisons indicate no significant differences in efficacy between anti-tumor
      necrosis factor (TNF) drugs. However, anti-TNF drugs appear to be more
      efficacious than anakinra, although not all comparisons reached statistical
      significance. Because of the lack of sound longterm safety data, evidence is
      insufficient to draw firm conclusions about the comparative safety of biologics.
      CONCLUSION: Anti-TNF drugs appear to be more efficacious than anakinra but do not
      differ significantly among each other. Clinical considerations such as
      comorbidities, route of administration, dosing regimens, and specific side effect
      profiles may guide the choice of an anti-TNF drug.

PMID- 17225296
TI  - PTSD and Vietnam Veterans.

PMID- 17225295
TI  - PTSD and Vietnam Veterans.

PMID- 17225297
TI  - Driven to distraction.

PMID- 17225299
TI  - [A frequent cause for acute gastroenteritis in winter].

PMID- 17225298
TI  - Is the burden worth the benefit of the Doctorate of Nursing (DNP) for NPs?
      Implications of Doctorate in Nursing Practice--still many unresolved issues for
      nurse practitioners.

PMID- 17225300
TI  - Gleason grading of prostate cancer in needle biopsies vs. radical prostatectomy
      specimens.

PMID- 17225301
TI  - How to prevent 500,000 heart attacks a year. Widespread screening for CVD could
      pinpoint who's vulnerable.

PMID- 17225302
TI  - Early Alzheimer's disease diagnosis gives hope. Detection in initial stages could
      slow progression, perhaps lead to prevention.

PMID- 17225303
TI  - Statin effective in preventing recurrent stroke.

PMID- 17225304
TI  - High blood pressure treatment may protect against dementia.

PMID- 17225305
TI  - Non-surgical way to heal severe heel pain. A new twist on an old exercise might
      bring relief from chronic plantar fasciitis.

PMID- 17225306
TI  - Four short walks better for hypertension than one long.

PMID- 17225307
TI  - Gene may play a role in macular degeneration.

PMID- 17225308
TI  - New recommendations for fibromyalgia relief. Heated pool therapy, certain
      medications among new treatments.

PMID- 17225309
TI  - Biologics--growing knowledge.

PMID- 17225310
TI  - DES ups daughter's breast cancer risk.

PMID- 17225311
TI  - A legacy of heart failure.

PMID- 17225312
TI  - I'm taking bisphosphonates for my osteoporosis, but I've heard it can cause a
      serious jaw condition. Is this something I should be concerned about?

PMID- 17225313
TI  - Anti-HIV agents. Starting therapy--three vs. four drugs.

PMID- 17225314
TI  - Anti-HIV agents. Atazanavir vs. Kaletra.

PMID- 17225315
TI  - Anti-HIV agents. Tipranavir in treatment-experienced PHAs.

PMID- 17225316
TI  - Anti-HIV agents. T-20 (enfurvirtide, Fuzeon).

PMID- 17225317
TI  - Anti-HIV agents. Five-year results from an NNRTI-based regimen.

PMID- 17225318
TI  - Infection fighters. Hepatitis C and HIV.

PMID- 17225320
TI  - Infection fighters. Hepatitis C--response to therapy at 12 weeks is the key to
      success.

PMID- 17225321
TI  - Side effects and complications. Uridine--effects on the liver and depression.

PMID- 17225319
TI  - Infection fighters. Hepatitis C--is a cure possible?

PMID- 17225322
TI  - Side effects and complications. Extended-release high-dose niacin helps lower
      lipid levels.

PMID- 17225323
TI  - Side effects and complications. Dying bones found in a small proportion of PHAs.

PMID- 17225324
TI  - Side effects and complications. Italian study explores reasons for sexual
      dysfunction in men.

PMID- 17225325
TI  - Side effects and complications. Swedes compare treatment switching with
      interruption.

PMID- 17225326
TI  - Know thy neighbor: a survey of diseases and complex syndromes that map to
      chromosomal regions encoding TRP channels.
AB  - On the basis of their ever-expanding roles, not only in sensory signaling but
      also in a plethora of other, often Ca(2+)-mediated actions in cell and whole body
      homeostasis, it is suggested that mutations in TRP channel genes not only cause
      disease states but also contribute in more subtle ways to simple and complex
      diseases. A survey is therefore presented of diseases and syndromes that map to
      one or multiple chromosomal loci containing TRP channel genes. A visual map of
      the chromosomal locations of TRP channel genes in man and mouse is also
      presented.

PMID- 17225327
TI  - [Suicidal behavior in a clinical population of 12-17-year olds with eating
      disorders].

PMID- 17225328
TI  - [A comment to the editorial: "Thrombelastography--should it be done and when?"].

PMID- 17225329
TI  - [Occupational stress?].

PMID- 17225330
TI  - [Aging of the population and public health].

PMID- 17225331
TI  - [A national vaccination strategy or 22 regional programs?].

PMID- 17225332
TI  - Do not resuscitate orders.

PMID- 17225333
TI  - The team had no options.

PMID- 17225334
TI  - Guiding light at the end of the tunnel.

PMID- 17225335
TI  - Making choices in an emergency room.

PMID- 17225336
TI  - The impact of China's one-child policy.

PMID- 17225337
TI  - People's voices on justice, equity and health care in India.

PMID- 17225338
TI  - Justice and placebo controls.

PMID- 17225339
TI  - Johnson v. Superior Court.

PMID- 17225341
TI  - Abstracts from the 8th International Congress on Aerobiology, 21-25 August 2006,
      Neuchatel, Switzerland.

PMID- 17225340
TI  - SIB 2006. Abstracts of the 51st National Congress of the Italian Society of
      Biochemistry and Molecular Biology, Riccione, Italy, 28-30 September 2006.

PMID- 17225342
TI  - Catholic Charities of Sacramento County v. Superior Court of Sacramento County.

PMID- 17225343
TI  - Planned Parenthood of Idaho v. Wasden.

PMID- 17225344
TI  - Tech talk. Keeping mobile computers mobile.

PMID- 17225345
TI  - [Abstracts of the 88th Congress of the Association of Morphologists, Nantes,
      France].

PMID- 17225346
TI  - J.F. v. D.B.

PMID- 17225347
TI  - Culliton v. Beth Israel Deaconess Medical Center.

PMID- 17225348
TI  - Consolidated index to volumes 1-13, 1993-2006.

PMID- 17225349
TI  - Resource guide 2007.

PMID- 17225351
TI  - Abstracts of the 32nd European Congress of Cytology, Venice, Italy, October 1-4,
      2006.

PMID- 17225350
TI  - Abbott v. Bragdon.

PMID- 17225352
TI  - Abstracts of the 1st World Congress of Public Health Nutrition and the 7th
      National Congress of the Spanish Society of Community Nutrition, Barcelona,
      Spain, 28-30 September 2006.

PMID- 17225353
TI  - Show me the money.
AB  - Universities are charities that have a duty to solicit help to fulfil their
      ambitions, both in the provision of education and in the conduct of research. If
      European higher education institutions are to compete effectively on a global
      scale, they must become as good at fundraising as their competitors in the United
      States.

PMID- 17225354
TI  - This place is big enough for both of us.

PMID- 17225355
TI  - What are superintegrons?

PMID- 17225356
TI  - Bibliography. Current world literature. Personality disorders and neuroses.

PMID- 17225357
TI  - [The place of Margaret of Navarre's Comedy of Four Women (1542) in the discourse
      on voluntary celibacy as a model of felicity from Ariosto to Gabrielle Suchon].

PMID- 17225358
TI  - [The theology of death on the eve of the modern period].

PMID- 17225359
TI  - [Death in the early modern period and medical anthropology].

PMID- 17225360
TI  - [Burial in the 16th century].

PMID- 17225361
TI  - [Opera as court celebration: between marriage and death].

PMID- 17225362
TI  - [Witness to the medical reality of the time: Le Mallade (ca. 1535) by Margaret of
      Navarre].

PMID- 17225363
TI  - [Ritual and ceremonial: funeral ceremonies in the courts of the nobility in the
      early modern period].

PMID- 17225364
TI  - [Widows in the early modern period: a study of the legal status and treatment of
      "visible" women in the Frydlant estate in northern Bohemia from 1550 to 1750].

PMID- 17225365
TI  - [The first Slovenian female scientists: educated Slovenian women from the Middle
      Ages to the first half of the 20th century].

PMID- 17225367
TI  - Research insights.
AB  - In any research study, the literature review and the theoretical or conceptual
      framework guide the development of the subsequent research questions and
      hypotheses. Both professional nurses and researchers evaluate the research
      article and its applicability to practice. This article presented the purpose of
      the theoretical framework or conceptual framework in a study, plus the purpose
      for the review of the literature.

PMID- 17225366
TI  - Bridging the generation gap.
AB  - Generational differences will always exist among nurses and patients. However,
      with our limited resources, the aging of our patient population, and increased
      longevity, it is pivotal that we identify effective strategies to transcend
      generational differences that may compromise patient care. By joining forces, we
      can maximize our knowledge and skills and in the process enhance our ability to
      value the contribution of these generational differences to improve quality
      nursing care and rehabilitation practice. Although the solutions may not be
      simple, we must persist in discovering creative solutions to overcome the
      multiple conflicts emerging from patient and nursing generational differences.

PMID- 17225368
TI  - Sticking together! A creative approach to documenting insulin double checks.
AB  - Patient care and family teaching are the heart of the rehabilitation staff
      nurse's role. Documentation of the various aspects of patient care and family
      teaching is a necessary but time-consuming process. In this article you will
      learn how the nurses of one rehabilitation center welcomed a creative time-saving
      method of working together to improve documentation compliance for double
      checking insulin administration. The development of the process, education of the
      staff and the outcomes are included.

PMID- 17225369
TI  - Relationship of RN role responsibilities to job satisfaction.
AB  - This study tested a delivery of care model that maximizes the role of the
      registered nurse in rehabilitation by providing care based on the scope of
      practice exclusive to the registered nurse and supplementing that practice with
      licensed and non-licensed support personnel. The model of care was developed as a
      response to the nursing shortage. The model attempts to best utilize the limited
      resource of registered nurse staffing. The nursing shortage is a national and
      global public health problem that is expected to intensify as the nursing
      population ages. The hypothesis was that when the rehabilitation registered nurse
      is allowed to function in areas for which they are exclusively trained, job
      satisfaction will significantly improve as long as there is sufficient support
      staff to provide for non-essential functions. The conceptual model for the study
      is based on Donabedian's model which demonstrates the relationship between
      satisfaction and patient outcomes. Results indicated that after an initial stage
      of discomfort resulting from a change in role expectations nurse satisfaction
      improved when registered nurses functioned within their exclusive scope of
      practice.

PMID- 17225370
TI  - Comparing two methods of rehabilitation for risk factor modification after a
      cardiac event.
AB  - Because fewer than half of cardiac patients in the United States enroll in
      cardiac rehabilitation (CR) programs, there is a critical need to test
      alternative strategies of delivering CR services. This study tested whether a
      home-based CR (home-CR) program was at least as effective as traditional-CR (trad
      CR) in the modification of coronary heart disease risk factors from the beginning
      of CR (baseline) to 2 and 4 months later. A repeated measures non-inferiority
      quasi-experimental design was used to examine changes in risk factors.
      Participants selected which CR program, traditional versus home-based, in which
      to participate: 37 patients chose trad-CR and 24 patients chose home-CR. The
      following indicators of risk factors were measured: smoking, blood pressure,
      frequency of aerobic exercise, cholesterol, amount of dietary fat, frequency of
      anger, body mass index (BMI), and waist circumference. Home-CR was found to be as
      effective as trad-CR in modification of cardiac risk factors including BMI, waist
      circumference, blood pressure, frequency of aerobic exercise, total cholesterol,
      and a low fat diet. Home-CR was not as effective as trad-CR in reducing the
      frequency of anger. These findings provide support for an alternative method of
      delivering cardiac rehabilitation services.

PMID- 17225371
TI  - Revision of the Rehabilitation Nursing Research Agenda.
AB  - In 2005, the board of directors of the Association of Rehabilitation Nurses (ARN)
      directed the Rehabilitation Nursing Foundation (RNF) to evaluate and revise the
      Rehabilitation Nursing Research Agenda. Following a review of the processes used
      by other nursing organizations to evaluate their research agendas, RNF first
      evaluated the effectiveness of the agenda, and then RNF embarked on a process to
      update and revise the agenda. The process included generating new and revised
      statements of research priorities based on the evaluation process, followed by a
      survey of members of ARN to rate the relevance of each statement to the
      profession. The results are a new Rehabilitation Nursing Research Agenda
      consisting of 19 statements of research priorities grouped into four categories.
      This new agenda has the potential to drive rehabilitation nursing research for
      the next 10 years.

PMID- 17225372
TI  - Physical activity barriers and program preferences among indigent internal
      medicine patients with arthritis.
AB  - The study purpose was to determine, among indigent arthritis patients, physical
      activity barriers, program preference frequencies and demographic associations. A
      structured interview of 223 indigent, internal medicine clinic patients with self
      reported arthritis was administered in a cross-sectional study design. The two
      most frequently reported barriers included bad health (52%) and pain (51%). The
      majority preferred to exercise alone (54%), close to home (76%), and in the early
      morning/evening (83%). The preferred method of receiving exercise information was
      by video or audio tape. Frequency of reported barriers was significantly
      associated with age, ethnicity, and gender; specific program preferences were
      significantly associated with age and gender only. Exercise programs for indigent
      patients with arthritis should be home-based with flexible scheduling.
      Educational material should include both video and audio tape formats. Future
      interventions should consider barriers related to poor health and pain while
      remaining responsive to age, gender, and ethnic differences. Nurses can play a
      pivotal role in such interventions.

PMID- 17225373
TI  - Perceived experience of caring for a wife with stroke.
AB  - This article presents a 55-year-old husband's perceived experience of caring for
      his wife with stroke, as learned from his 1 year of participation in a Web-based
      support intervention study. In a secondary analysis of data, his narrative
      entries (n = 213) were coded and drawn to Friedemann's framework of systemic
      organization. The themes that emerged from these data were that of the caregiver
      providing support, offering solutions, and taking control. Friedemann's system
      maintenance process dimension was the area that captured most of his experience,
      which indicated that this caregiver spent a significant amount of his energy in
      creating control and stability within his environment to maintain congruence or
      balance in his life. These findings can be used to identify and design
      interventions, which for male spousal caregivers, affect the quality of their
      lives.

PMID- 17225374
TI  - High-frequency hearing in phocid and otariid pinnipeds: an interpretation based
      on inertial and cochlear constraints (L).
AB  - Audiograms in air and underwater, determined by previous workers for four
      pinniped species, two eared seals (Otariidae) and two phocids (Phocidae), are
      supplemented here by measurements on their middle ear ossicular mass, enabling
      mechanistic interpretations of high-frequency hearing and audiogram differences.
      Otariid hearing is not largely affected by the medium (air/water). This indicates
      that cochlear constraints limit high-frequency hearing in otariids. Phocids,
      however, have massive middle ear ossicles, and underwater hearing has radically
      shifted towards higher frequencies. This suggests that the high-frequency hearing
      of phocids in air is constrained by ossicle inertia.

PMID- 17225375
TI  - A note on the low-frequency noise reduction of cylindrical capsules (L).
AB  - The noise reductions provided by capsules consisting of uniform cylindrical
      shells whose two ends are closed off by like circular plates are analyzed for the
      low-frequency regime in which a capsule acts quasi-statically, much like a
      pressure vessel. The change in the confined volume is determined from the
      structural deflections produced by a net pressure difference, taking account of
      the interactions of the shell and end plates. Expressions for the noise reduction
      of a single capsule and of two nested capsules are derived. Some insights into
      the noise reduction effects of interaction between the shell and end plates are
      discussed, as are the contributions of these components.

PMID- 17225376
TI  - Lateralization of sine tones-interaural time vs phase (L).
AB  - Listeners estimated the lateral positions of 50 sine tones with interaural phase
      differences ranging from -150 degrees to +150 degrees and with different
      frequencies, all in the range where signal fine structure supports
      lateralization. The estimates indicated that listeners lateralize sine tones on
      the basis of interaural time differences and not interaural phase differences.

PMID- 17225377
TI  - Acoustic beams with angular momentum.
AB  - A family of exact solutions of the Helmholtz equation is used to represent
      transversely bounded helicoidal sound beams. Simple results are obtained for the
      energy content per unit length, the momentum content per unit length, and the
      angular momentum content per unit length. The analysis is restricted to lossless
      media; scattering and viscous damping are neglected. The energy, momentum, and
      angular momentum are calculated to second order in the velocity potential. The
      angular momentum content is always equal to m/omega times the energy content,
      where m (an integer) is the topological charge and omega is the angular
      frequency.

PMID- 17225378
TI  - Anomalous postcritical refraction behavior for certain transversely isotropic
      media.
AB  - Snell's law at the boundary between two transversely isotropic media with a
      vertical axis of symmetry (VTI media) can be solved by setting up a fourth order
      polynomial for the sine of the reflection/transmission angles. This approach
      reveals the possible presence of an anomalous postcritical angle for certain
      transversely isotropic media. There are thus possibly three incident angle
      regimes for the reflection/refraction of longitudinal or transverse waves
      incident upon a VTI medium: precritical, postcritical/preanomalous, and
      postanomalous. The anomalous angle occurs for certain strongly anisotropic media
      where the required root to the phase velocity equation must be switched in order
      to obey Snell's law. The reflection/transmission coefficients, polarization
      directions, and the phase velocity are all affected by both the anisotropy and
      the incident angle. The incident critical angles are also effected by the
      anisotropy.

PMID- 17225379
TI  - Finite element analysis of broadband acoustic pulses through inhomogenous media
      with power law attenuation.
AB  - Acoustic waves in tissues and weakly attenuative fluids often have an attenuation
      parameter, alpha(omega), satisfying alpha(omega)= alpha0omegay in which alpha0 is
      a constant, omega is the frequency, and y is between 1 and 2. This power law
      attenuation is not predicted by the classical thermoviscous wave equation and
      researchers have proposed different modified viscous wave equations in which the
      loss term is a convolution operator or a fractional spatial or temporal
      derivative. In this paper, acoustic waves undergoing power law attenuation are
      modeled by a modification to the thermoviscous wave equation in which the time
      derivative of the viscous term is replaced by a fractional time derivative. An
      explicit time domain, finite element formulation leads to a stable algorithm
      capable of simulating axisymmetric, broadband acoustic pulses propagating through
      attenuative and dispersive media. The algorithm does not depend on the Born
      approximation, long wavelength limit, or plane wave assumptions. The algorithm is
      validated for planar and focused transducers and results include radiation
      patterns from a viscous scatterer in a lossless background and signals reflected
      from a viscous layer. The program can be used to determine scattering parameters
      for large, strong, possibly viscous scatterers, in either a lossless or viscous
      background, for which analytic results are scarce.

PMID- 17225380
TI  - Stability of self-similar plane shocks with Hertzian nonlinearity.
AB  - The nonlinear progressive wave equation [McDonald and Kuperman, J. Acoust. Soc.
      Am. 81, 1406-1417 (1987)] is expressed in a form to accommodate Hertzian
      nonlinearity of order n=3/2 typical of granular media. Stability of self-similar
      plane weak shocks against perturbations in three dimensions is demonstrated for
      arbitrary order nonlinearity with 1 <n <3. Investigation of stability in the
      presence of Hertzian nonlinearity is motivated by the nonlinearity coefficient
      being arbitrarily large in the unstressed state. Energy in the perturbation field
      is shown to fall off at least as fast as 1/t, while energy in the self-similar
      wave falls off slower than 1/t. For an initial wave profile increasing in the
      direction of propagation, it is shown that where the quadratic nonlinearity
      coefficient diverges, the slope of the wave goes to zero.

PMID- 17225381
TI  - Application of a nonlinear boundary condition model to adhesion interphase damage
      and failure.
AB  - In an earlier paper [J. Sadler, B. O'Neill, and R. Maev, J. Acoust. Soc. Am. 118,
      51-59 (2005)], a set of generalized boundary conditions were proposed, based on a
      thin layer (thickness << wavelength) model of the acoustic interface. In this
      paper, the model is extended to cover the more pathological nonlinearity of the
      adhesion interphase-that is, the critically important thin layer where bonds are
      formed between adhesive and substrate. First, the boundary conditions are shown
      to be sufficiently general to cope with all manner of interphase nonlinearity,
      including unilateral cases such as clapping or slipping. To maintain this
      generality, an analytic time domain solution is proposed based on expansion in
      terms of the layer thickness rather than the conventional expansion in terms of
      harmonics. Finally, the boundary conditions are applied to an interphase failure
      model based upon basic continuum damage mechanics principles. It is proposed that
      such a model, which can predict the evolution of the interphase damage under
      stressful conditions, may allow a proper prediction of the ultimate adhesion
      strength based on nonlinear parameters measured nondestructively with ultrasound.

PMID- 17225382
TI  - Axial radiation force of a bessel beam on a sphere and direction reversal of the
      force.
AB  - An expression is derived for the radiation force on a sphere placed on the axis
      of an ideal acoustic Bessel beam propagating in an inviscid fluid. The expression
      uses the partial-wave coefficients found in the analysis of the scattering when
      the sphere is placed in a plane wave traveling in the same external fluid. The
      Bessel beam is characterized by the cone angle beta of its plane wave components
      where beta=0 gives the limiting case of an ordinary plane wave. Examples are
      found for fluid spheres where the radiation force reverses in direction so the
      force is opposite the direction of the beam propagation. Negative axial forces
      are found to be correlated with conditions giving reduced backscattering by the
      beam. This condition may also be helpful in the design of acoustic tweezers for
      biophysical applications. Other potential applications include the manipulation
      of objects in microgravity. Islands in the (ka, beta) parameter plane having a
      negative radiation force are calculated for the case of a hexane drop in water.
      Here k is the wave number and a is the drop radius. Low frequency approximations
      to the radiation force are noted for rigid, fluid, and elastic solid spheres in
      an inviscid fluid.

PMID- 17225383
TI  - Precursor arrivals in the Yellow Sea, their distinction from first-order head
      waves, and their geoacoustic inversion.
AB  - Measurements made as part of the 1996 Yellow Sea experiment at location 37
      degrees N, 124 degrees E, undertaken by China and the U.S. are analyzed. Signals
      generated by explosive sources were received by a 60-m-length vertical line array
      deployed in waters 75 m deep. Evidence is presented that precursor arrivals
      measured at ranges less than 1 km are refracted waves that are zeroth order in
      their ray series classification, and this directly points to the existence of a
      gradient in sediment sound speed. In contrast, first-order head waves, which are
      much weaker in amplitude, would exist only if this gradient were absent. It is
      found that the energy spectrum of precursor arrivals agrees well with a zeroth
      order model, i.e., it is proportional to the source amplitude spectrum, S(f),
      where f is frequency, rather than a first-order model, which would have it
      proportional to S(f)/f. From travel time analysis the sediment sound speed just
      below the water-sediment interface is estimated to be 1573 m/s with a gradient of
      1.1 s(-1), and from analysis of the energy spectrum of the precursor arrivals the
      sediment attenuation is estimated to be 0.08 dB/m/kHz over the frequency range
      150-420 Hz. The results apply to a nominal sediment depth of 100 m.

PMID- 17225384
TI  - Generalization of the rotated parabolic equation to variable slopes.
AB  - The rotated parabolic equation [J. Acoust. Soc. Am. 87, 1035-1037 (1990)] is
      generalized to problems involving ocean-sediment interfaces of variable slope.
      The approach is based on approximating a variable slope in terms of a series of
      constant slope regions. The original rotated parabolic equation algorithm is used
      to march the field through each region. An interpolation-extrapolation approach
      is used to generate a starting field at the beginning of each region beyond the
      one containing the source. For the elastic case, a series of operators is applied
      to rotate the dependent variable vector along with the coordinate system. The
      variable rotated parabolic equation should provide accurate solutions to a large
      class of range-dependent seismo-acoustics problems. For the fluid case, the
      accuracy of the approach is confirmed through comparisons with reference
      solutions. For the elastic case, variable rotated parabolic equation solutions
      are compared with energy-conserving and mapping solutions.

PMID- 17225385
TI  - Simulations of large acoustic scintillations in the straits of Florida.
AB  - Using a full-wave acoustic model, Monte Carlo numerical studies of intensity
      fluctuations in a realistic shallow water environment that simulates the Straits
      of Florida, including internal wave fluctuations and bottom roughness, have been
      performed. Results show that the sound intensity at distant receivers
      scintillates dramatically. The acoustic scintillation index SI increases rapidly
      with propagation range and is significantly greater than unity at ranges beyond
      about 10 km. This result supports a theoretical prediction by one of the authors.
      Statistical analyses show that the distribution of intensity of the random wave
      field saturates to the expected Rayleigh distribution with SI= 1 at short range
      due to multipath interference effects, and then SI continues to increase to large
      values. This effect, which is denoted supersaturation, is universal at long
      ranges in waveguides having lossy boundaries (where there is differential mode
      attenuation). The intensity distribution approaches a log-normal distribution to
      an excellent approximation; it may not be a universal distribution and comparison
      is also made to a K distribution. The long tails of the log-normal distribution
      cause "acoustic intermittency" in which very high, but rare, intensities occur.

PMID- 17225386
TI  - Acoustic scattering from mud volcanoes and carbonate mounds.
AB  - Submarine mud volcanoes occur in many parts of the world's oceans and form an
      aperture for gas and fluidized mud emission from within the earth's crust. Their
      characteristics are of considerable interest to the geology, geophysics,
      geochemistry, and underwater acoustics communities. For the latter, mud volcanoes
      are of interest in part because they pose a potential source of clutter for
      active sonar. Close-range (single-interaction) scattering measurements from a mud
      volcano in the Straits of Sicily show scattering 10-15 dB above the background.
      Three hypotheses were examined concerning the scattering mechanism: (1) gas
      entrained in sediment at/near mud volcano, (2) gas bubbles and/or particulates
      (emitted) in the water column, (3) the carbonate bio-construction covering the
      mud volcano edifice. The experimental evidence, including visual, acoustic, and
      nonacoustic sensors, rules out the second hypothesis (at least during the
      observation time) and suggests that, for this particular mud volcano the dominant
      mechanism is associated with carbonate chimneys on the mud volcano. In terms of
      scattering levels, target strengths of 4-14 dB were observed from 800 to 3600 Hz
      for a monostatic geometry with grazing angles of 3-5 degrees. Similar target
      strengths were measured for vertically bistatic paths with incident and scattered
      grazing angles of 3-5 degrees and 33-50 degrees, respectively.

PMID- 17225387
TI  - Subcritical scattering from buried elastic shells.
AB  - Buried objects have been largely undetectable by traditional high-frequency
      sonars due to their insignificant bottom penetration. Further, even a high
      grazing angle sonar approach is vastly limited by the coverage rate dictated by
      the finite water depth, making the detection and classification of buried objects
      using low frequency, subcritical sonar an interesting alternative. On the other
      hand, such a concept would require classification clues different from the
      traditional high-resolution imaging and shadows to maintain low false alarm
      rates. A potential alternative, even for buried targets, is classification based
      on the acoustic signatures of man-made elastic targets. However, the elastic
      responses of buried and proud targets are significantly different. The objective
      of this work is to identify, analyze, and explain some of the effects of the
      sediment and the proximity of the seabed interface on the scattering of sound
      from completely and partially buried elastic shells. The analysis was performed
      using focused array processing of data from the GOATS98 experiment carried out
      jointly by MIT and SACLANTCEN, and a new hybrid modeling capability combining a
      virtual source-or wave-field superposition-approach with an exact spectral
      integral representation of the Green's functions for a stratified ocean
      waveguide, incorporating all multiple scattering between the object and the
      seabed. Among the principal results is the demonstration of the significant role
      of structural circumferential waves in converting incident, evanescent waves into
      backscattered body waves, emanating to the receivers at supercritical grazing
      angles, in effect making the target appear closer to the sonar than predicted by
      traditional ray theory.

PMID- 17225388
TI  - A comparison of broadband models for sand sediments.
AB  - Chotiros and Isakson [J. Acoust. Soc. Am. 116(4), 2011-2022 (2004)] recently
      proposed an extension of the Biot-Stoll model for poroelastic sediments that
      makes predictions for compressional wave speed and attenuation, which are in much
      better accord with the experimental measurements of these quantities extant in
      the literature than either those of the conventional Biot-Stoll model or the
      rival model of Buckingham [J. Acoust. Soc. Am. 108(6), 2796-2815 (2000)]. Using a
      local minimizer, the Nelder-Mead simplex method, it is shown that there are
      generally at least two choices of the Chotiros-Isakson parameters which produce
      good agreement with experimental measurements. Since one postulate of the
      Chotiros-Isakson model is that, due to the presence of air bubbles in the pore
      space, the pore fluid compressibility is greater than that of water, an
      alternative model based on a conjecture by Biot [J. Acoust. Soc. Am. 34(5), 1254
      1264 (1962)], air bubble resonance, is considered. While this model does as well
      or better than the Chotiros-Isakson model in predicting measured values of wave
      speed and attenuation, the Rayleigh-Plesset theory of bubble oscillation casts
      doubt on its plausibility as a general explanation of large dispersion of
      velocity with respect to frequency.

PMID- 17225389
TI  - Observations of polarized seismoacoustic T waves at and beneath the seafloor in
      the abyssal Pacific ocean.
AB  - Combined seismic and hydrophone observations show that the traditional T wave
      propagates as a seismoacoustic polarized interface wave (Ti) coupled to the
      seafloor. Seismoacoustic Ti waves propagating at the sound speed of water are
      routinely observed over megameter distances at the deep (4979 m) seafloor Hawaii
      2 Observatory (H2O) between Hawaii and California, even though the seafloor site
      is within a shadow zone for acoustic wave propagation. Ti has also been observed
      on seismometers 225 km SSW of Oahu at the OSN1 site at the seafloor and within an
      ODP borehole into the basalt basement. Analyses of timing, apparent velocity,
      energy, and polarization of these interface waves are presented. At low frequency
      (< approximately 5 Hz) Ti propagates dominantly in the sediments and is
      consistent with higher-mode Rayleigh waves. At higher frequencies the observed Ti
      waves dominantly propagate acoustically with characteristics suggesting local
      scattering. The observation of Ti from an earthquake in Guatemala at OSN1, whose
      path is blocked by the Island of Hawaii, is consistent with scattering from the
      vicinity of the Cross Seamount.

PMID- 17225390
TI  - Geoacoustic inversion of short range source data using a plane wave reflection
      coefficient approach.
AB  - Acoustic time series data were collected in a shallow, hard bottom lake
      environment located in central Texas using both short range (2 m) implosive data,
      obtained with the source and a single hydrophone located near mid-depth in the
      waveguide, along with longer range implosive and explosive data from a near
      surface source to a bottom mounted hydrophone. Matched field inversions using
      simulated annealing were performed with a ray trace plus complex plane wave
      reflection coefficient forward propagation model that was validated in previous
      work. Isolating bottom interacting paths to perform the inversions is shown to be
      essential to reduce parameter uncertainties in the hard bottom environment and
      enables a systematic approach to the inversions which establishes the number of
      layers needed to represent the lake environment. Measured transmission loss data
      from a towed source were compared through a RMS error analysis to modeled
      transmission loss, constructed with the parameters from inversions of data from
      several source types, to further establish the validity of the inversion approach
      for this environment. Geoacoustic parameters obtained by inversions of short
      range, low frequency impulsive data are used to predict transmission loss at
      longer ranges and higher frequencies. The range dependence of the global minimum
      is discussed.

PMID- 17225391
TI  - Noise suppression using the coherent onion peeler.
AB  - An innovative noise suppression algorithm, called the coherent onion peeler (COP)
      (patent detained) is derived by minimizing the error in the coherent subtraction
      of the data from a single plane wave model. The COP solution "collapses" for all
      beamforming algorithms to the same solution at the complex hydrophone FFT level.
      Thus, any beamformer can be applied to the residual FFTs after the COP has been
      applied. The COP is applied to the strongest interferer first and the residual
      FFTs represent the acoustic field with this interferer coherently "peeled back"
      like the outer skin of an onion. This procedure can be repeated any number of
      times to coherently suppress the noise from all interferers present. A new
      nonadaptive beamformer is developed that "blends" together the best beam pattern
      properties of conventional beamforming (CBF) near array design frequency and the
      generalized fourier integral method (GFIM) at very low frequencies (VLF). In
      between these frequency extremes, the GFIM-CBF Blend (patent pending) (G-C Blend)
      is a frequency-dependent weighted average of both individual beamformers. COP and
      G-C Blend are applied to the broadband noise emitted by the tow ship, which
      severely degrades the performance of the towed array; COP reduced this broadband
      noise by over 19 dB in a single pass.

PMID- 17225392
TI  - Active control of passive acoustic fields: passive synthetic aperture/Doppler
      beamforming with data from an autonomous vehicle.
AB  - The maneuverability of autonomous underwater vehicles (AUVs) equipped with hull
      mounted arrays provides the opportunity to actively modify received acoustic
      fields to optimize extraction of information. This paper uses ocean acoustic data
      collected by an AUV-mounted two-dimensional hydrophone array, with overall
      dimension one-tenth wavelength at 200-500 Hz, to demonstrate aspects of this
      control through vehicle motion. Source localization is performed using Doppler
      shifts measured at a set of receiver velocities by both single elements and a
      physical array. Results show that a source in the presence of a 10-dB higher
      level interferer having exactly the same frequency content (as measured by a
      stationary receiver) is properly localized and that white-noise-constrained
      adaptive beamforming applied to the physical aperture data in combination with
      Doppler beamforming provides greater spatial resolution than physical-aperture
      alone beamforming and significantly lower sidelobes than single element Doppler
      beamforming. A new broadband beamformer that adjusts for variations in vehicle
      velocity on a sample by sample basis is demonstrated with data collected during a
      high-acceleration maneuver. The importance of including the cost of energy
      expenditure in determining optimal vehicle motion is demonstrated through
      simulation, further illustrating how the vehicle characteristics are an integral
      part of the signal/array processing structure.

PMID- 17225393
TI  - Studying the mechanical behavior of a plastic, shock-resisting, antitank
      landmine.
AB  - Modal behavior in landmines has recently become a topic of interest for acoustic
      landmine detection. It is well known that landmines exhibit mechanical resonance
      behavior that enhances the soil velocity over a buried landmine. Recent
      experimental work by Zagrai et al. [A. Zagrai, D. Donskoy, and A. Ekimov, J.
      Acoust. Soc. Am. 118 (6), 3619-3628 (2005)] demonstrates the existence of
      structural modes in several landmines. The work reported herein parallels the
      work of Zagrai et al. in studying the structural modes of the pressure plate of a
      plastic, cylindrically symmetric, antitank landmine. The pressure plate is
      considered to act as an elastically supported thin elastic plate. An observed
      perturbation of the first symmetric mode of the pressure plate is caused by the
      landmine's shock-resisting mechanism. This is validated by a lumped element model
      for the first symmetric mode coupled to the shock-resisting mechanism.

PMID- 17225394
TI  - Computation of the homogeneous and forced solutions of a finite length, line
      driven, submerged plate.
AB  - A formulation is developed to predict the vibration response of a finite length,
      submerged plate due to a line drive. The formulation starts by describing the
      fluid in terms of elliptic cylinder coordinates, which allows the fluid loading
      term to be expressed in terms of Mathieu functions. By moving the fluid loading
      term to the right-hand side of the equation, it is considered to be a force. The
      operator that remains on the left-hand side is the same as that of the in vacuo
      plate: a fourth-order, constant coefficient, ordinary differential equation.
      Therefore, the problem appears to be an inhomogeneous ordinary differential
      equation. The solution that results has the same form as that of the in vacuo
      plate: the sum of a forced solution, and four homogeneous solutions, each of
      which is multiplied by an arbitrary constant. These constants are then chosen to
      satisfy the structural boundary conditions on the two ends of the plate. Results
      for the finite plate are compared to the infinite plate in both the wave number
      and spatial domains. The theoretical predictions of the plate velocity response
      are also compared to results from finite element analysis and show reasonable
      agreement over a large frequency range.

PMID- 17225395
TI  - On formulation of a transition matrix for electroporoelastic medium and
      application to analysis of scattered electroseismic wave.
AB  - On the basis of Pride's theory (1994) which couples Biot's theory for poroelastic
      medium (1956) and Maxwell equations via flux/force transport equations, we extend
      Yeh et al. (2004) approach for poroelastic medium to develop a transition matrix
      for electroporoelastic medium. The transition matrix, which relates the
      coefficients of scattered waves to those of incident waves, is then derived
      through the application of Betti's third identity and the associated
      orthogonality conditions for the electroporoelastic medium. To illustrate the
      application, a simple case of the scattering problem of a spherical
      electroporoelastic inclusion, embedded within the surrounding electroporoelastic
      medium subjected to an incident plane compressional wave is considered.

PMID- 17225396
TI  - Study of the comparison of the methods of equivalent sources and boundary element
      methods for near-field acoustic holography.
AB  - Boundary element methods (BEM) based near-field acoustic holography (NAH) has
      been used successfully in order to reconstruct the normal velocity on an
      arbitrarily shaped structure surface from measurements of the pressure field on a
      nearby conformal surface. An alternative approach for this reconstruction on a
      general structure utilizes the equivalent sources method (ESM). In ESM the
      acoustic field is represented by a set of point sources located over a surface
      that is close to the structure surface. This approach is attractive mainly for
      its simplicity of implementation and speed. In this work ESM as an approximation
      of BEM based NAH is studied and the necessary conditions for the successful
      application of this approach in NAH is discussed. A cylindrical fuselage surface
      excited by a point force as an example to validate the results is used.

PMID- 17225397
TI  - Impact of perforation impedance on the transmission loss of reactive and
      dissipative silencers.
AB  - The effect of perforation impedance on the acoustic behavior of reactive and
      dissipative silencers is investigated using experimental and computational
      approaches. The boundary element method (BEM) is applied for the prediction of
      transmission loss of silencers with different perforation geometries. The
      variations are considered in the porosity (8.4 and 25.7%) and hole diameter
      (0.249 and 0.498 cm) of perforations for both reactive and dissipative silencers,
      as well as the fiber filling density (100 and 200 kg/m3) for the latter. The
      acoustic impedance for a number of perforations in contact with air alone and
      fibrous material has been incorporated into the predictions, which are then
      compared with the measured transmission loss using an impedance tube setup. The
      results demonstrate the significance of the accuracy of the perforation impedance
      in the predictions for both reactive and dissipative silencers.

PMID- 17225398
TI  - A laboratory investigation of noise reduction by riblike structures on the
      ground.
AB  - This paper investigates the use of periodically spaced edges or wells for the
      control of road traffic noise. The wells have uniform height and width and are
      placed on the ground. Physical scale modeling is used to assess the acoustic
      performance of these structures under laboratory conditions. It is shown that, in
      certain situations where the use of conventional barriers would not be
      appropriate, strategically designed riblike structures can provide insertion
      losses of typically 10-15 dB. The findings are explained in terms of acoustic
      scattering with the approaches used in the study of resonators and
      diffraction/interference gratings.

PMID- 17225399
TI  - Orthogonal adaptation for multichannel feedforward control.
AB  - In active noise control, it is desired to generate destructive interference by
      model-independent control. This is possible for single-channel systems to which a
      recently proposed method, called orthogonal adaptation, is applicable. In this
      study, the new method is extended to multichannel systems. An important issue is
      how to optimize a feedforward controller in the minimum H2 norm sense. In
      practice, secondary paths of some multichannel systems may be nonminimum phase.
      It is a difficult problem to design H2 feedforward controllers for multichannel
      systems with nonminimum phase secondary paths. The problem is solved analytically
      here with the best achievable, a practical and an economical solution. A
      recursive least squares algorithm is presented for online identification of
      multiple paths without persistent excitations. These solutions make it possible
      to implement noninvasive mode-independent controllers for multichannel systems.
      Experiment results are presented to verify the analytical results.

PMID- 17225400
TI  - Geometrical perturbation of an inclined wall on decay times of acoustic modes in
      a trapezoidal cavity with an impedance surface.
AB  - Decay times of acoustic modes of a trapezoidal cavity (TC modes) with an inclined
      wall are studied. Each cavity wall is successively assigned an impedance surface
      and the other five walls are rigid. The decay times are obtained from the
      coupling between rigid-walled modes of the rectangular cavity (RC modes) that
      bounds the trapezoidal cavity. Two coupling mechanisms are identified, namely,
      the damping coupling and the geometrical coupling. The former is related to the
      coupling of RC modes at the impedance surface, while the latter is related to the
      coupling of RC modes at the inclined wall. Both mechanisms include the same
      volume coupling where RC modes couple throughout the trapezoidal cavity. When the
      impedance surface is at either of the two trapezoidal walls, the grouping of TC
      modes with same decay times and the decay time variation with the wall
      inclination are determined only by the damping coupling. When the surface is at
      any of the other rectangular walls, both the damping and geometrical couplings
      are at work. This paper provides an understanding of how the inclined wall and
      the impedance surface location affect the TC-mode grouping, and what determines
      the decay time variation with the inclination.

PMID- 17225401
TI  - Evaluation of decay times in coupled spaces: an efficient search algorithm within
      the Bayesian framework.
AB  - This paper discusses an efficient method for evaluating multiple decay times
      within the Bayesian framework. Previous works [N. Xiang and P. M. Goggans, J.
      Acoust. Soc. Am. 110, 1415-1424 (2001); 113, 2685-2697 (2003); N. Xiang, P. M.
      Goggans, T. Jasa, and M. Kleiner, 117, 3707-3715 (2005)] have applied the
      Bayesian inference to cope with demanding tasks in estimating multiple decay
      times from Schroeder decay functions measured or calculated in acoustically
      coupled spaces. Since then a number of recent works call for efficient estimation
      methods within the Bayesian framework. An efficient analysis is of practical
      significance for better understanding and modeling the sound energy decay process
      in acoustically coupled spaces or even in single spaces for reverberation time
      estimation. This paper will first formulate the Bayesian posterior probability
      distribution function (PPDF) in a matrix form to reduce the dimensionality as
      applied to the decay time evaluation. Based on existence of only global extremes
      of PPDFs as observed from extensive experimental data, this paper describes a
      dedicated search algorithm for an efficient estimation of decay times.

PMID- 17225402
TI  - Modal decomposition method for acoustic impedance testing in square ducts.
AB  - Accurate duct acoustic propagation models are required to predict and reduce
      aircraft engine noise. These models ultimately rely on measurements of the
      acoustic impedance to characterize candidate engine nacelle liners. This research
      effort increases the frequency range of normal-incidence acoustic impedance
      testing in square ducts by extending the standard two-microphone method (TMM),
      which is limited to plane wave propagation, to include higher-order modes. The
      modal decomposition method (MDM) presented includes four normal modes in the
      model of the sound field, thus increasing the bandwidth from 6.7 to 13.5 kHz for
      a 25.4 mm square waveguide. The MDM characterizes the test specimen for normal-
      and oblique-incident acoustic impedance and mode scattering coefficients. The MDM
      is first formulated and then applied to the measurement of the reflection
      coefficient matrix for a ceramic tubular specimen. The experimental results are
      consistent with results from the TMM for the same specimen to within the 95%
      confidence intervals for the TMM. The MDM results show a series of resonances for
      the ceramic tubular material exhibiting a monotonic decrease in the resonant
      peaks of the acoustic resistance with increasing frequency, resembling a rigidly
      terminated viscous tube, and also evidence of mode scattering is visible at the
      higher frequencies.

PMID- 17225403
TI  - Objectively measured and subjectively perceived distortion in nonlinear systems.
AB  - A method for measuring nonlinear distortion, which is applicable to almost any
      transmission system and which can use any input signal as a test signal, is
      proposed. The method exploits the fact that a pair of signals, generated to form
      the real and imaginary parts of the analytical signal corresponding to the input
      signal to a system, lose their property of being a Hilbert pair after being
      passed through a nonlinear system. The method was tested by measuring 12
      different hearing aid compression systems. These objective measurements were
      compared with the subjectively perceived amount of distortion, assessed by a
      group of 10 otologically normal subjects. A reasonably monotonic relation between
      the subjective and objective measures of distortion was observed. The objective
      Hilbert pair based measure can be related to both traditional total harmonic
      distortion and traditional signal to noise ratio.

PMID- 17225404
TI  - Optimum beamformer in correlated source environments.
AB  - A new method for overcoming signal cancellation problems due to correlated
      interferences which occur in a minimum variance distortionless response
      beamformer is proposed. Instead of decorrelating the correlated interferences,
      the coherently combining signal-to-interference plus noise ratio (CC-SINR)
      beamformer regards them as replicas of the desired signal and coherently combines
      them with the desired signal. This method uses an eigenvector constraint that
      suppresses only noise and uncorrelated interferences but retains the desired
      signal and correlated interferences. The CC-SINR beamformer does not require any
      preliminary information on correlated interferences. The signal-to-interference
      plus noise ratio (SINR) of the proposed beamformer output was compared to that of
      a conventional SINR beamformer when correlated interference, uncorrelated
      interference, and white noise exist. In addition, various key parameters that
      affect the performance of the beamformer, such as signal-to-noise ratio,
      uncorrelated interference-to-noise ratio, angular separation between signals,
      attenuation factor, phase delay of correlated interference, and the number of
      sensors were analyzed. All of the experimental results were in good agreement
      with the analytical results.

PMID- 17225405
TI  - Noniterative analytical formula for inverse scattering of multiply scattering
      point targets.
AB  - This paper derives, in the exact framework of multiple scattering theory for
      point targets, a noniterative analytical formula for the nonlinear inversion of
      the target scattering strengths from the scattering or response matrix that can
      be applied after the target positions have been estimated in a previous step via,
      e.g., time-reversal multiple signal classification or another approach. The new
      formula provides a noniterative analytical alternative to the iterative numerical
      solution approach for the same problem presented in a recent paper [A. J.
      Devaney, E. A. Marengo, and F. K. Gruber, "Time-reversal-based imaging and
      inverse scattering of multiply scattering point targets," J. Acoust. Soc. Am.
      118, 3129-3138 (2005)]. The two methods (noniterative versus iterative) are
      comparatively investigated with two numerical examples.

PMID- 17225406
TI  - A nonlinear finite-element model of the newborn ear canal.
AB  - A three-dimensional nonlinear finite-element model of a 22-day-old newborn ear
      canal is presented. The geometry is based on a clinical x-ray CT scan. A
      nonlinear hyperelastic constitutive law is applied to model large deformations.
      The Young's modulus of the soft tissue is found to have a significant effect on
      the ear-canal volume change, which ranges from approximately 27% to 75% over the
      static-pressure range of +/-3kPa. The effects of Poisson's ratio and of the ratio
      C10: C01 in the hyperelastic model are found to be small. The volume changes do
      not reach a plateau at high pressures, which implies that the newborn ear-canal
      wall would not be rigid in tympanometric measurements. The displacements and
      volume changes calculated from the model are compared with available experimental
      data.

PMID- 17225407
TI  - Laser interferometry measurements of middle ear fluid and pressure effects on
      sound transmission.
AB  - An otitis media with effusion model in human temporal bones with two laser
      vibrometers was created in this study. By measuring the displacement of the
      stapes from the medial side of the footplate, the transfer function of the middle
      ear, which is defined as the displacement transmission ratio (DTR) of the
      tympanic membrane to footplate, was derived under different middle ear pressure
      and fluid in the cavity with a correction factor for cochlear load. The results
      suggest that the DTR increases with increasing frequency up to 4k Hz when the
      middle ear pressure was changing from 0 to 20 or -20 cm H20 (e.g., +/-196 daPa)
      and fluid level was increasing from 0 to a full middle ear cavity. The positive
      and negative pressures show different effects on the DTR. The effect of fluid on
      DTR varies between three frequency ranges: f < 1k, between 1k and 4k, and f > 4k
      Hz. These findings show how the efficiency of the middle ear system for sound
      transmission changes during the presence of fluid in the cavity and variations of
      middle ear pressure.

PMID- 17225408
TI  - Columella footplate motion and the cochlear microphonic potential in the embryo
      and hatchling chicken.
AB  - A piezoelectric (PZE) vibrator was used to mechanically drive the columella
      footplate and stimulate the cochlea of chicken embryos and hatchlings. Our
      objectives were to characterize the motion of the PZE driver and determine the
      relationship between columella footplate motion (displacement/ velocity) and the
      cochlear microphonic recorded from the recessus scala tympani (CMrst). At each
      frequency, displacement of the PZE driver probe tip was linearly related to the
      applied voltage over a wide range of attenuation levels (-60 to -20 dBre:50 Vp
      p). The mean displacement across frequencies (100-4000 Hz) was 0.221+/-0.042
      micromp-p for a constant applied voltage level of -20 dBre:50 Vp-p. Displacement
      was within 1.5 dB of the mean for this stimulus level at all frequencies except
      for 4000 Hz, where it was approximately 3 dB higher (p < 0.01). CMrst amplitudes
      in hatchlings were larger than amplitudes in embryos (p=0.003). For a given
      frequency, CM was linearly related to footplate displacement and velocity at both
      ages. The transform ratio of CMrst/A (CM amplitude/displacement) increased at
      approximately 6 dB/octave at frequencies between 100 and 1000 Hz in hatchlings
      suggesting that cochlear impedance (Zc) was resistive at these frequencies. In a
      large fraction of the embryos, Zc exhibited reactive behavior.

PMID- 17225409
TI  - L1,L2 maps of distortion-product otoacoustic emissions from a moth ear with only
      two auditory receptor neurons.
AB  - The tympanal organ of the moth Empyreuma affinis emits physiologically vulnerable
      distortion-product otoacoustic emissions. To assess the nature of underlying
      mechanical nonlinearities, we measured L1,L2 maps by varying both stimulus
      levels. Two types of maps were found: (1) Maps containing dominant islands
      centered at the L1=L2 diagonal as it is typical for saturating nonlinearities
      that can be described by Boltzmann functions. In contrast to maps published for
      mammals and frogs, the shape of such islands includes sharp ridges at L1 or L2
      levels close to 70 dB sound pressure level. This could be produced by a strongly
      asymmetric operating point of the respective transfer functions, consistent with
      the fact that the auditory sensory cells are not hair cells but primary
      mechanoreceptors with a single cilium. The saturating map components could be
      selectively reduced by acoustic suppression. (2) Maps where separated islands
      were less conspicuous but in which the dominant feature consisted of contour
      lines which were orthogonal to the L1=2L2 diagonal and could be generated by an
      expansive nonlinearity. Maps showing strong islands were found for f2 frequencies
      between 26.7 and 45 kHz, maps without strong islands for f2 between 42 and 57.5
      kHz. This suggests a frequency-dependent change regarding the involved mechanical
      nonlinearities.

PMID- 17225410
TI  - Effects of middle-ear immaturity on distortion product otoacoustic emission
      suppression tuning in infant ears.
AB  - Distortion product otoacoustic emission (DPOAE) measures of cochlear function,
      including DPOAE suppression tuning curves and input/output (I/O) functions, are
      not adultlike in human infants. These findings suggest the cochlear amplifier
      might be functionally immature in newborns. However, many noncochlear factors
      influence DPOAEs and must be considered. This study examines whether age
      differences in DPOAE I/O functions recorded from infant and adult ears reflect
      maturation of ear-canal/middle-ear function or cochlear mechanics. A model based
      on linear middle-ear transmission and nonlinear cochlear generation was developed
      to fit the adult DPOAE I/O data. By varying only those model parameters related
      to middle-ear transmission (and holding cochlear parameters at adult values), the
      model successfully fitted I/O data from infants at birth through age 6 months.
      This suggests that cochlear mechanics are mature at birth. The model predicted an
      attenuation of stimulus energy through the immature ear canal and middle ear, and
      evaluated whether immaturities in forward transmission could explain the
      differences consistently observed between infant and adult DPOAE suppression.
      Results show that once the immaturity was compensated for by providing infants
      with a relative increase in primary tone level, DPOAE suppression tuning at f2=
      6000 Hz was similar in adults and infants.

PMID- 17225411
TI  - Role of suppression and retro-cochlear processes in comodulation masking release.
AB  - Recent physiological studies suggest that comodulation masking release (CMR)
      could be a consequence of wideband inhibition at the level of the cochlear
      nucleus. The present study investigates whether the existence region of
      psychophysical CMR is comparable to the inhibitory areas of units showing a
      physiological correlate of CMR. Since the inhibitory areas are similar to
      suppressive regions at the level of the basilar membrane, the amount of CMR that
      can be accounted for by suppression was determined by predicting the data with a
      model incorporating a peripheral nonlinearity. A CMR of up to 6 dB could still be
      experimentally observed for a flanking band (FB) four octaves below the on
      frequency masker (OFM). For FB frequencies below the OFM, the suggested model
      predicts CMR equal to the measured CMR for high levels of the FB. The model
      underestimates the magnitude of CMR for midlevels of the FB, indicating that
      suppression alone cannot account for CMR. The data are consistent with the
      hypothesis that wideband inhibition plays a role in CMR.

PMID- 17225413
TI  - Virtual pitch in a computational physiological model.
AB  - A computational model of nervous activity in the auditory nerve, cochlear
      nucleus, and inferior colliculus is presented and evaluated in terms of its
      ability to simulate psychophysically-measured pitch perception. The model has a
      similar architecture to previous autocorrelation models except that the
      mathematical operations of autocorrelation are replaced by the combined action of
      thousands of physiologically plausible neuronal components. The evaluation
      employs pitch stimuli including complex tones with a missing fundamental
      frequency, tones with alternating phase, inharmonic tones with equally spaced
      frequencies and iterated rippled noise. Particular attention is paid to
      differences in response to resolved and unresolved component harmonics. The
      results indicate that the model is able to simulate qualitatively the related
      pitch-perceptions. This physiological model is similar in many respects to
      autocorrelation models of pitch and the success of the evaluations suggests that
      autocorrelation models may, after all, be physiologically plausible.

PMID- 17225412
TI  - Molecular analysis of the effect of relative tone level on multitone pattern
      discrimination.
AB  - Molecular psychophysics attempts to model the observer's response to stimuli as
      they vary from trial to trial. The approach has gained popularity in multitone
      pattern discrimination studies as a means of estimating the relative reliance or
      decision weight listeners give to different tones in the pattern. Various factors
      affecting decision weights have been examined, but one largely ignored is the
      relative level of tones in the pattern. In the present study listeners detected a
      level-increment in a sequence of 5, 100-ms, 2.0-kHz tone bursts alternating in
      level between 40 and 80 dB SPL. The level increment was made largest on the 40-dB
      tones, yet despite this all four highly-practiced listeners gave near exclusive
      weight to the 80-dB tones. The effect was the same when the tones were replaced
      by bursts of broadband Gaussian noise alternating in level. It was reduced only
      when the level differences were made <10 dB, and it was entirely reversed only
      when the low-level tones alternated with louder bursts of Gaussian noise. The
      results are discussed in terms of the effects of both sensory and perceptual
      factors on estimates of decision weights.

PMID- 17225414
TI  - A test of the binaural equal-loudness-ratio hypothesis for tones.
AB  - It is well known that a tone presented binaurally is louder than the same tone
      presented monaurally. It is less clear how this loudness ratio changes as a
      function of level. The present experiment was designed to directly test the
      Binaural Equal-Loudness-Ratio hypothesis (BELRH), which states that the loudness
      ratio between equal-SPL monaural and binaural tones is independent of SPL. If
      true, the BELRH implies that monaural and binaural loudness functions are
      parallel when plotted on a log scale. Cross-modality matches between string
      length and loudness were used to directly measure binaural and monaural loudness
      functions for nine normal listeners. Stimuli were 1-kHz 200-ms tones ranging in
      level from 5 dB SL to 100 dB SPL. A two-way ANOVA showed significant effects of
      level and mode (binaural or monaural) on loudness, but no interaction between the
      level and mode. Consequently, no significant variations were found in the
      binaural-to-monaural loudness ratio across the range of levels tested. This
      finding supports the BELRH. In addition, the present data were found to closely
      match loudness functions derived from binaural level differences for equal
      loudness using the model proposed by Whilby et al. [J. Acoust. Soc. Am. 119, 3931
      3939 (2006)].

PMID- 17225415
TI  - Binaural comodulation masking release: effects of masker interaural correlation.
AB  - Binaural detection was examined for a signal presented in a narrow band of noise
      centered on the on-signal masking band (OSB) or in the presence of flanking noise
      bands that were random or comodulated with respect to the OSB. The noise had an
      interaural correlation of 1.0 (No), 0.99 or 0.95. In No noise, random flanking
      bands worsened Spi detection and comodulated bands improved Spi detection for
      some listeners but had no effect for other listeners. For the 0.99 or 0.95
      interaural correlation conditions, random flanking bands were less detrimental to
      Spi detection and comodulated flanking bands improved Spi detection for all
      listeners. Analyses based on signal detection theory indicated that the
      improvement in Spi thresholds obtained with comodulated bands was not compatible
      with an optimal combination of monaural and binaural cues or to across-frequency
      analyses of dynamic interaural phase differences. Two accounts consistent with
      the improvement in Spi thresholds in comodulated noise were (1) envelope
      information carried by the flanking bands improves the weighting of binaural cues
      associated with the signal; (2) the auditory system is sensitive to across
      frequency differences in ongoing interaural correlation.

PMID- 17225417
TI  - The kurtosis metric as an adjunct to energy in the prediction of trauma from
      continuous, nonGaussian noise exposures.
AB  - Data from an earlier study [Hamernik et al. (2003). J. Acoust. Soc. Am. 114, 386
      395] were consistent in showing that, for equivalent energy [Leq= 100 dB(A)] and
      spectra, exposure to a continuous, nonGaussian (nonG) noise could produce
      substantially greater hearing and sensory cell loss in the chinchilla model than
      a Gaussian (G) noise exposure and that the statistical metric, kurtosis, computed
      on the amplitude distribution of the noise could order the extent of the trauma.
      This paper extends these results to Leq= 90 and 110 dB(A), and to nonG noises
      that are generated using broadband noise bursts, and band limited impacts within
      a continuous G background noise. Data from nine new experimental groups with 11
      or 12 chinchillas/group is presented. Evoked response audiometry established
      hearing thresholds and surface preparation histology quantified sensory cell
      loss. At the lowest level [Leq=90 dB(A)] there were no differences in the trauma
      produced by G and nonG exposures. For Leq >90 dB(A) nonG exposures produced
      increased trauma relative to equivalent G exposures. Removing energy from the
      impacts by limiting their bandwidth reduced trauma. The use of noise bursts to
      produce the nonG noise instead of impacts also reduced the amount of trauma.

PMID- 17225418
TI  - Individual differences in the sensitivity to pitch direction.
AB  - It is commonly assumed that one can always assign a direction-upward or downward
      to a percept of pitch change. The present study shows that this is true for some,
      but not all, listeners. Frequency difference limens (FDLs, in cents) for pure
      tones roved in frequency were measured in two conditions. In one condition, the
      task was to detect frequency changes; in the other condition, the task was to
      identify the direction of frequency changes. For three listeners, the
      identification FDL was about 1.5 times smaller than the detection FDL, as
      predicted (counterintuitively) by signal detection theory under the assumption
      that performance in the two conditions was limited by one and the same internal
      noise. For three other listeners, however, the identification FDL was much larger
      than the detection FDL. The latter listeners had relatively high detection FDLs.
      They had no difficulty in identifying the direction of just-detectable changes in
      intensity, or in the frequency of amplitude modulation. Their difficulty in
      perceiving the direction of small frequency/pitch changes showed up not only when
      the task required absolute judgments of direction, but also when the directions
      of two successive frequency changes had to be judged as identical or different.

PMID- 17225416
TI  - Electromotile hearing: acoustic tones mask psychophysical response to high
      frequency electrical stimulation of intact guinea pig cochleae.
AB  - When sinusoidal electric stimulation is applied to the intact cochlea, a
      frequency-specific acoustic emission can be recorded in the ear canal. Acoustic
      emissions are produced by basilar membrane motion, and have been used to suggest
      a corresponding acoustic sensation termed "electromotile hearing." Electromotile
      hearing has been specifically attributed to electric stimulation of outer hair
      cells in the intact organ of Corti. To determine the nature of the auditory
      perception produced by electric stimulation of a cochlea with intact outer hair
      cells, guinea pigs were tested in a psychophysical task. First, subjects were
      trained to report detection of sinusoidal acoustic stimuli and dynamic range was
      assessed using response latency. Subjects were then implanted with a ball
      electrode placed into scala tympani. Following the surgical implant procedure,
      subjects were transferred to a task in which acoustic signals were replaced by
      sinusoidal electric stimulation, and dynamic range was assessed again. Finally,
      the ability of acoustic pure-tone stimuli to mask the detection of the electric
      signals was assessed. Based on the masking effects, it is concluded that
      sinusoidal electric stimulation of the intact cochlea results in perception of a
      tonal (rather than a broadband or noisy) sound at a frequency of 8 kHz or above.

PMID- 17225419
TI  - The relationship between frequency selectivity and pitch discrimination: effects
      of stimulus level.
AB  - Three experiments tested the hypothesis that fundamental frequency (fo)
      discrimination depends on the resolvability of harmonics within a tone complex.
      Fundamental frequency difference limens (fo DLs) were measured for random-phase
      harmonic complexes with eight fo's between 75 and 400 Hz, bandpass filtered
      between 1.5 and 3.5 kHz, and presented at 12.5-dB/component average sensation
      level in threshold equalizing noise with levels of 10, 40, and 65 dB SPL per
      equivalent rectangular auditory filter bandwidth. With increasing level, the
      transition from large (poor) to small (good) fo DLs shifted to a higher fo. This
      shift corresponded to a decrease in harmonic resolvability, as estimated in the
      same listeners with excitation patterns derived from measures of auditory filter
      shape and with a more direct measure that involved hearing out individual
      harmonics. The results are consistent with the idea that resolved harmonics are
      necessary for good fo discrimination. Additionally, fo DLs for high fo's
      increased with stimulus level in the same way as pure-tone frequency DLs,
      suggesting that for this frequency range, the frequencies of harmonics are more
      poorly encoded at higher levels, even when harmonics are well resolved.

PMID- 17225420
TI  - The relationship between frequency selectivity and pitch discrimination:
      sensorineural hearing loss.
AB  - This study tested the relationship between frequency selectivity and the minimum
      spacing between harmonics necessary for accurate fo discrimination. Fundamental
      frequency difference limens (fo DLs) were measured for ten listeners with
      moderate sensorineural hearing loss (SNHL) and three normal-hearing listeners for
      sine- and random-phase harmonic complexes, bandpass filtered between 1500 and
      3500 Hz, with fo's ranging from 75 to 500 Hz (or higher). All listeners showed a
      transition between small (good) fo DLs at high fo's and large (poor) fo DLs at
      low fo's, although the fo at which this transition occurred (fo,tr) varied across
      listeners. Three measures thought to reflect frequency selectivity were
      significantly correlated to both the fo,tr and the minimum fo DL achieved at high
      fo's: (1) the maximum fo for which fo DLs were phase dependent, (2) the maximum
      modulation frequency for which amplitude modulation and quasi-frequency
      modulation were discriminable, and (3) the equivalent rectangular bandwidth of
      the auditory filter, estimated using the notched-noise method. These results
      provide evidence of a relationship between fo discrimination performance and
      frequency selectivity in listeners with SNHL, supporting "spectral" and "spectro
      temporal" theories of pitch perception that rely on sharp tuning in the auditory
      periphery to accurately extract fo information.

PMID- 17225422
TI  - Constructing and disrupting listeners' models of auditory space.
AB  - A major problem for an auditory system exposed to sound in a reverberant
      environment is to distinguish reflections from true sound sources. Previous
      research indicates that the process of recognizing reflections is malleable from
      moment to moment. Three experiments report how ongoing input can prevent or
      disrupt the fusion of the delayed sound with the direct sound, a necessary
      component of the precedence effect. The buildup of fusion can be disrupted by
      presenting stimuli in alternation that simulate different reflecting surfaces. If
      buildup of fusion is accomplished first and then followed by an aberrant
      configuration, breakdown of the precedence effect occurs but it depends on the
      duration of the new sound configuration. The Djelani and Blauert (2001) finding
      that a brief disruption has no effect on fusion was confirmed; however, it was
      found that a more lengthy disruption produces breakdown.

PMID- 17225421
TI  - The influence of later-arriving sounds on the ability of listeners to judge the
      lateral position of a source.
AB  - This study examined the deleterious effects of a later-arriving sound on the
      processing of interaural differences of time (IDTs) from a preceding sound. A
      correlational analysis assessed the relative weight given to IDTs of source and
      echo clicks for echo delays of 1-64 ms when the echo click was attenuated
      relative to the source click (0-36 dB). Also measured were proportion correct and
      the proportion of responses predicted from the weights. The IDTs of source and
      echo clicks were selected independently from Gaussian distributions (mu=0 s,
      sigma = 100/s). Listeners were instructed to indicate the laterality of the
      source click. Equal weight was given to the source and echo clicks for echo
      delays of 64 ms with no echo attenuation. For echo delays of 16-64 ms,
      attenuating the echo had no substantial effect on source weight or proportion
      correct until the echo was attenuated by 18-30 dB. At echo delays < or =4 ms,
      source weights and proportions correct remained high regardless of echo
      attenuation. The proportions of responses predicted from the weights were lower
      at echo delays > or =16 ms. Results were discussed in terms of backward
      recognition masking and binaural sluggishness and compared to measurements of
      echo disturbance.

PMID- 17225423
TI  - Amplitude modulation of turbulence noise by voicing in fricatives.
AB  - The two principal sources of sound in speech, voicing and frication, occur
      simultaneously in voiced fricatives as well as at the vowel-fricative boundary in
      phonologically voiceless fricatives. Instead of simply overlapping, the two
      sources interact. This paper is an acoustic study of one such interaction effect:
      the amplitude modulation of the frication component when voicing is present.
      Corpora of sustained and fluent-speech English fricatives were recorded and
      analyzed using a signal-processing technique designed to extract estimates of
      modulation depth. Results reveal a pattern, consistent across speaking style,
      speaker, and place of articulation, for modulation at fo to rise at low voicing
      strengths and subsequently saturate. Voicing strength needed to produce
      saturation varied 60-66 dB across subjects and experimental conditions.
      Modulation depths at saturation varied little across speakers but significantly
      for place of articulation (with [z] showing particularly strong modulation)
      clustering at approximately 0.4-0.5 (a 40%-50% fluctuation above and below
      unmodulated amplitude); spectral analysis of modulating signals revealed weak but
      detectable modulation at the second and third harmonics (i.e., 2fo and 3fo).

PMID- 17225424
TI  - Effect of intonation on cantonese lexical tones.
AB  - In tonal languages, there are potential conflicts between the FO-based changes
      due to the coexistence of intonation and lexical tones. In the present study, the
      interaction of tone and intonation in Cantonese was examined using acoustic and
      perceptual analyses. The acoustic patterns of tones at the initial, medial, and
      final positions of questions and statements were measured. Results showed that
      intonation affects both the FO level and contour, while the duration of the six
      tones varied as a function of positions within intonation contexts. All six tones
      at the final position of questions showed rising FO contour, regardless of their
      canonical form. Listeners were overall more accurate in the identification of
      tones presented within the original carrier than of the same tones in isolation.
      However, a large proportion of tones 33, 21, 23, and 22 at the final position of
      questions were misperceived as tone 25 both within the original carrier and as
      isolated words. These results suggest that although the intonation context
      provided cues for correct tone identification, the intonation-induced changes in
      FO contour cannot always be perceptually compensated for, resulting in some
      erroneous perception of the identity of Cantonese tone.

PMID- 17225425
TI  - Extended speech intelligibility index for the prediction of the speech reception
      threshold in fluctuating noise.
AB  - The extension to the speech intelligibility index (SII; ANSI S3.5-1997 (1997))
      proposed by Rhebergen and Versfeld [Rhebergen, K.S., and Versfeld, N.J. (2005).
      J. Acoust. Soc. Am. 117(4), 2181-2192] is able to predict for normal-hearing
      listeners the speech intelligibility in both stationary and fluctuating noise
      maskers with reasonable accuracy. The extended SII model was validated with
      speech reception threshold (SRT) data from the literature. However, further
      validation is required and the present paper describes SRT experiments with
      nonstationary noise conditions that are critical to the extended model. From
      these data, it can be concluded that the extended SII model is able to predict
      the SRTs for the majority of conditions, but that predictions are better when the
      extended SII model includes a function to account for forward masking.

PMID- 17225426
TI  - Vowel recognition via cochlear implants and noise vocoders: effects of formant
      movement and duration.
AB  - Previous work has demonstrated that normal-hearing individuals use fine-grained
      phonetic variation, such as formant movement and duration, when recognizing
      English vowels. The present study investigated whether these cues are used by
      adult postlingually deafened cochlear implant users, and normal-hearing
      individuals listening to noise-vocoder simulations of cochlear implant
      processing. In Experiment 1, subjects gave forced-choice identification judgments
      for recordings of vowels that were signal processed to remove formant movement
      and/or equate vowel duration. In Experiment 2, a goodness-optimization procedure
      was used to create perceptual vowel space maps (i.e., best exemplars within a
      vowel quadrilateral) that included F1, F2, formant movement, and duration. The
      results demonstrated that both cochlear implant users and normal-hearing
      individuals use formant movement and duration cues when recognizing English
      vowels. Moreover, both listener groups used these cues to the same extent,
      suggesting that postlingually deafened cochlear implant users have category
      representations for vowels that are similar to those of normal-hearing
      individuals.

PMID- 17225427
TI  - Isolating the energetic component of speech-on-speech masking with ideal time
      frequency segregation.
AB  - When a target speech signal is obscured by an interfering speech wave form,
      comprehension of the target message depends both on the successful detection of
      the energy from the target speech wave form and on the successful extraction and
      recognition of the spectro-temporal energy pattern of the target out of a
      background of acoustically similar masker sounds. This study attempted to isolate
      the effects that energetic masking, defined as the loss of detectable target
      information due to the spectral overlap of the target and masking signals, has on
      multitalker speech perception. This was achieved through the use of ideal time
      frequency binary masks that retained those spectro-temporal regions of the
      acoustic mixture that were dominated by the target speech but eliminated those
      regions that were dominated by the interfering speech. The results suggest that
      energetic masking plays a relatively small role in the overall masking that
      occurs when speech is masked by interfering speech but a much more significant
      role when speech is masked by interfering noise.

PMID- 17225428
TI  - Perceptual adaptation by normally hearing listeners to a simulated "hole" in
      hearing.
AB  - Simulations of cochlear implants have demonstrated that the deleterious effects
      of a frequency misalignment between analysis bands and characteristic frequencies
      at basally shifted simulated electrode locations are significantly reduced with
      training. However, a distortion of frequency-to-place mapping may also arise due
      to a region of dysfunctional neurons that creates a "hole" in the tonotopic
      representation. This study simulated a 10 mm hole in the mid-frequency region.
      Noise-band processors were created with six output bands (three apical and three
      basal to the hole). The spectral information that would have been represented in
      the hole was either dropped or reassigned to bands on either side. Such
      reassignment preserves information but warps the place code, which may in itself
      impair performance. Normally hearing subjects received three hours of training in
      two reassignment conditions. Speech recognition improved considerably with
      training. Scores were much lower in a baseline (untrained) condition where
      information from the hole region was dropped. A second group of subjects trained
      in this dropped condition did show some improvement; however, scores after
      training were significantly lower than in the reassignment conditions. These
      results are consistent with the view that speech processors should present the
      most informative frequency range irrespective of frequency misalignment.

PMID- 17225429
TI  - Statistical analysis of the autoregressive modeling of reverberant speech.
AB  - Hands-free speech input is required in many modern telecommunication applications
      that employ autoregressive (AR) techniques such as linear predictive coding. When
      the hands-free input is obtained in enclosed reverberant spaces such as typical
      office rooms, the speech signal is distorted by the room transfer function. This
      paper utilizes theoretical results from statistical room acoustics to analyze the
      AR modeling of speech under these reverberant conditions. Three cases are
      considered: (i) AR coefficients calculated from a single observation; (ii) AR
      coefficients calculated jointly from an M-channel observation (M > 1); and (iii)
      AR coefficients calculated from the output of a delay-and sum beamformer. The
      statistical analysis, with supporting simulations, shows that the spatial
      expectation of the AR coefficients for cases (i) and (ii) are approximately equal
      to those from the original speech, while for case (iii) there is a discrepancy
      due to spatial correlation between the microphones which can be significant. It
      is subsequently demonstrated that at each individual source-microphone position
      (without spatial expectation), the M-channel AR coefficients from case (ii)
      provide the best approximation to the clean speech coefficients when microphones
      are closely spaced (<0.3m).

PMID- 17225430
TI  - Binaural segregation in multisource reverberant environments.
AB  - In a natural environment, speech signals are degraded by both reverberation and
      concurrent noise sources. While human listening is robust under these conditions
      using only two ears, current two-microphone algorithms perform poorly. The
      psychological process of figure-ground segregation suggests that the target
      signal is perceived as a foreground while the remaining stimuli are perceived as
      a background. Accordingly, the goal is to estimate an ideal time-frequency (T-F)
      binary mask, which selects the target if it is stronger than the interference in
      a local T-F unit. In this paper, a binaural segregation system that extracts the
      reverberant target signal from multisource reverberant mixtures by utilizing only
      the location information of target source is proposed. The proposed system
      combines target cancellation through adaptive filtering and a binary decision
      rule to estimate the ideal T-F binary mask. The main observation in this work is
      that the target attenuation in a T-F unit resulting from adaptive filtering is
      correlated with the relative strength of target to mixture. A comprehensive
      evaluation shows that the proposed system results in large SNR gains. In
      addition, comparisons using SNR as well as automatic speech recognition measures
      show that this system outperforms standard two-microphone beamforming approaches
      and a recent binaural processor.

PMID- 17225431
TI  - Model-based sound synthesis of the guqin.
AB  - This paper presents a model-based sound synthesis algorithm for the Chinese
      plucked string instrument called the guqin. The instrument is fretless, which
      enables smooth pitch glides from one note to another. A version of the digital
      waveguide synthesis approach is used, where the string length is time-varying and
      its energy is scaled properly. A body model filter is placed in cascade with the
      string model. Flageolet tones are synthesized with the so-called ripple filter
      structure, which is an FIR comb filter in the delay line of a digital waveguide
      model. In addition, signal analysis of recorded guqin tones is presented.
      Friction noise produced by gliding the finger across the soundboard has a
      harmonic structure and is proportional to the gliding speed. For pressed tones,
      one end of a vibrating string is terminated either by the nail of the thumb or a
      fingertip. The tones terminated with a fingertip decay faster than those
      terminated with a thumb. Guqin tones are slightly inharmonic and they exhibit
      phantom partials. The synthesis model takes into account these characteristic
      features of the instrument and is able to reproduce them. The synthesis model
      will be used for rule based synthesis of guqin music.

PMID- 17225432
TI  - Long-time temperature rise due to absorption of focused gaussian beams in tissue.
AB  - An analytical technique previously developed to study tissue displacement due to
      acoustic radiation force is extended to analyze temperature rise in tissue for
      exposure times that are comparable to, or longer than, the tissue perfusion time.
      A focused transducer with Gaussian amplitude shading is assumed to radiate into a
      perfused tissue medium with constant thermal and acoustic properties. A simple
      closed-form expression is derived for the steady-state temperature rise, and a
      transient correction term is constructed that allows for computation of the
      equilibrium time of the medium. Comparisons with temperature calculations for non
      Gaussian transducers show that the model may be applied to more general intensity
      profiles.

PMID- 17225433
TI  - Whistle variability in South Atlantic spinner dolphins from the Fernando de
      Noronha archipelago off Brazil.
AB  - A series of quali- and quantitative analyses were conducted to evaluate the
      variability of spinner dolphin whistles from the Fernando de Noronha Archipelago
      off Brazil. Nine variables were extracted from each whistle contour, and the
      whistle contours shapes were classified into the seven categories described in
      Driscoll (1995). The analysis showed mean beginning and ending frequencies values
      of 10.78 and 12.74 kHz, respectively. On average, whistle duration was relatively
      short, with mean values around 0.495 s (N=702). Comparative analyses were also
      conducted to investigate the relationship between the obtained results and those
      presented in previous studies. When comparing averages, the results of the study
      of Oswald et al.(2003) in the Tropical Eastern Pacific (TEP) presented less
      significant differences in relation to this study; only whistle duration differed
      significantly between both works. The results of multivariate classification
      tests also pointed TEP population as the closest related to the population
      studied here. The similarities between such disjunct populations might be
      attributed to a more recent isolation event (the closing of the Panama Isthmus)
      than the divergence that has driven North and South Atlantic populations apart.

PMID- 17225434
TI  - Cepstral coefficients and hidden Markov models reveal idiosyncratic voice
      characteristics in red deer (Cervus elaphus) stags.
AB  - Bouts of vocalizations given by seven red deer stags were recorded over the
      rutting period, and homomorphic analysis and hidden Markov models (two techniques
      typically used for the automatic recognition of human speech utterances) were
      used to investigate whether the spectral envelope of the calls was individually
      distinctive. Bouts of common roars (the most common call type) were highly
      individually distinctive, with an average recognition percentage of 93.5%. A
      "temporal" split-sample approach indicated that although in most individuals
      these identity cues held over the rutting period, the ability of the models
      trained with the bouts of roars recorded early in the rut to correctly classify
      later vocalizations decreased as the recording date increased. When Markov models
      trained using the bouts of common roars were used to classify other call types
      according to their individual membership, the classification results indicated
      that the cues to identity contained in the common roars were also present in the
      other call types. This is the first demonstration in mammals other than primates
      that individuals have vocal cues to identity that are common to the different
      call types that compose their vocal repertoire.

PMID- 17225435
TI  - Variation in the hearing sensitivity of a dolphin population determined through
      the use of evoked potential audiometry.
AB  - A portable electrophysiological data collection system was used to assess hearing
      in a captive population of bottlenose dolphins by recording auditory evoked
      potentials (AEPs). The AEP system used a transducer embedded in a suction cup to
      deliver amplitude modulated tones to the dolphin through the lower jaw. Evoked
      potentials were recorded noninvasively using surface electrodes. Adaptive
      procedures allowed hearing thresholds to be estimated from 10 to 150 kHz in a
      single ear in about 45 min. Hearing thresholds were measured in 42 bottlenose
      dolphins (28 male, 14 female), ranging in age from 4 to 47 years. Variations in
      hearing sensitivity with age and sex followed patterns seen in humans and
      terrestrial mammals: generally, within the population there was a progressive
      loss of high frequency hearing with age and an earlier onset of hearing loss in
      males than in females. Hearing loss generally occurred between the ages of 20 and
      30, and all animals over the age of 27 had some degree of hearing loss. Two
      dolphins with profound hearing loss were found within the population. Aberrant
      hearing patterns were observed in related dolphins suggesting genetic links to
      hearing ability may exist.

PMID- 17225436
TI  - Modeling acoustic propagation of airgun array pulses recorded on tagged sperm
      whales (Physeter macrocephalus).
AB  - In 2002 and 2003, tagged sperm whales (Physeter macrocephalus) were
      experimentally exposed to airgun pulses in the Gulf of Mexico, with the tags
      providing acoustic recordings at measured ranges and depths. Ray trace and
      parabolic equation (PE) models provided information about sound propagation paths
      and accurately predicted time of arrival differences between multipath arrivals.
      With adequate environmental information, a broadband acoustic PE model predicted
      the relative levels of multipath arrivals recorded on the tagged whales. However,
      lack of array source signature data limited modeling of absolute received levels.
      Airguns produce energy primarily below 250 Hz, with spectrum levels about 20-40
      dB lower at 1 kHz. Some arrivals recorded near the surface in 2002 had energy
      predominantly above 500 Hz; a surface duct in the 2002 sound speed profile helps
      explain this effect, and the beampattern of the source array also indicates an
      increased proportion of high-frequency sound at near-horizontal launch angles.
      These findings indicate that airguns sometimes expose animals to measurable sound
      energy above 250 Hz, and demonstrate the influences of source and environmental
      parameters on characteristics of received airgun pulses. The study also
      illustrates that on-axis source levels and simple geometric spreading
      inadequately describe airgun pulse propagation and the extent of exposure zones.

PMID- 17225438
TI  - Synthesis of audio spectra using a diffraction model.
AB  - It is shown that the intensity variations of an audio signal in the frequency
      domain can be obtained by using a mathematical function containing a series of
      weighted complex Bessel functions. With proper choice of values for two
      parameters, this function can transform an input spectrum of discrete frequencies
      of unit intensity into the known spectra of different musical instruments.
      Specific examples of musical instruments are considered for evaluating the
      performance of this method. It is found that this function yields musical spectra
      with a good degree of accuracy.

PMID- 17225437
TI  - Acoustic response from adherent targeted contrast agents.
AB  - In ultrasonic molecular imaging, encapsulated micron-sized gas bubbles are
      tethered to a blood vessel wall by targeting ligands. A challenging problem is to
      detect the echoes from adherent microbubbles and distinguish them from echoes
      from nonadherent agents and tissue. Echoes from adherent contrast agents are
      observed to include a high amplitude at the fundamental frequency, and
      significantly different spectral shape compared with free agents (p <0.0003).
      Mechanisms for the observed acoustical difference and potential techniques to
      utilize these differences for molecular imaging are proposed.

PMID- 17225439
TI  - Geometrical effects on the tuning of Chinese and Korean stone chimes.
AB  - The vibrational mode frequencies and mode shapes of ancient stone chimes are
      analyzed and their dependence on stone shapes are discussed. Mode shapes and
      frequencies of several chime models are determined by using finite element
      methods, and these show good agreement with mode shapes and frequencies observed
      in Korean pyeongyeong chime stones using holographic interferometry and
      experimental modal testing. The dependence of mode shapes and frequencies on
      vertex angle and base curvature suggests that the geometries used in late Chinese
      bianqing and Korean pyeongyeong may have been selected to give the best sound.

PMID- 17225440
TI  - The acoustic signature of bubbles fragmenting in sheared flow.
AB  - Measurements of the sound of bubbles fragmenting in fluid shear are presented and
      analyzed. The frequency, amplitude, and decay rate of the acoustic emissions from
      1.8-mm-radius bubbles fragmenting between opposed fluid jets have been
      determined. A broad band of frequencies (1.8 to 30 kHz) is observed with peak
      pressure amplitudes in the range of 0.03 to 2 Pa. While the peak pressure
      amplitudes show no significant scaling with frequency, the frequency dependence
      of the decay rates is consistent with the sum of thermal and acoustic radiation
      losses.

PMID- 17225441
TI  - [Postoperative abdominal tumor: a diagnostic dilemma].

PMID- 17225442
TI  - "Just ascites"?

PMID- 17225443
TI  - [Medicine and research: an indissoluble relationship].

PMID- 17225444
TI  - [Prevalence of liver diseases in a small rural community isolated in the mountain
      heights: clinical, biochemical and ultrasonographic study].
AB  - The goal of this population-based clinical, biochemical and ultrasonographic
      study was to assess the prevalence of liver diseases in Lara, a small rural
      community isolated in the mountain heights of Tucuman, a Province of Argentina
      with the highest reported rates of HAV infection in children. Inhabitants of Lara
      lack electricity, potable water and a sewer system. The study included 102
      individuals representing 41% of the total population. Anti-HBc and anti-HCV were
      negative in all cases. No children showed clinical, biochemical or ecographic
      abnormalities. Among adults, 41% referred alcohol consumption and 12% blood
      transfusions. Only 3 adults (6%) had mildly elevated ALT. Ultrasound showed
      steatosis in 8 individuals (16%), gallstones in 7 (14%), parenchymal micro
      calcifications in 5 (10%) and parasitic cysts in 4 (8%). Prevalence of HAV
      infection in Lara was 89% in adults and 35% in children, being significantly
      lower than that of children of medium/high (53%, p = 0.05) and low (74%, p =
      0.0006) socioeconomic level from the city of Tucuman (control groups). These
      differences were more marked in children aged < 5 years (anti-HAV in 0%, 53% and
      75% respectively). Serologic tests for echinoccocal disease were positive in 3/4
      individuals with parasitic cysts, 2/5 with micro-calcifications and 17/85 (20%)
      with normal ultrasound, thus suggesting a high rate of false-positive results of
      the Elisa test utilized. This study showed that in Lara there is a high
      prevalence of steatosis, gallstones and equinoccocal disease in adults, absence
      of HBVand HCV infection and low exposure to HAV in children especially in those
      aged < 5 years.

PMID- 17225445
TI  - [Duration of viremia and fecal shedding of the virus in hepatitis A infected
      children].
AB  - Hepatitis A virus (HAV) infection is endemic in Argentina. Molecular tools have
      allowed HAV RNA detection to be extent to sera and feces from patients with
      different clinical backgrounds. We compare the sensitivity of the RT-PCR protocol
      we follow using primers targeting different genomic regions and VP3 C terminal
      was the most sensitive. Sequential sera and fecal samples were obtained from 20
      children with acute self limited Hepatitis A. HAV RNA was detectable in 18/20
      children if sera and stool specimens were collected at the onset of symptoms and
      in 19/20 if a later sample was considered. HAV RNA was detectable in serum from
      9/20 patients until day 30 and in feces from 2 patients until day 60 and until
      day 90 in one. Genomic sequences from VP1/2A region in 8 samples showed they all
      belong to subgenotype IA although they were different between them. HAV RNA was
      detectable only in 1/11 sera from children with acute liver failure when VP3 C
      terminal fragment was searched and it belonged to genotype I. Universal
      vaccination in one year old children was recently implemented in Argentina and it
      will dramatically enable the decrease of the viral circulation, making new
      sources of infection emerge and allowing the introduction of new genotypes. The
      application of molecular tools to the study of the natural history of infection
      and to the epidemiologic surveillance may contribute to efficient control and
      lead to rational decisions in public health policies.

PMID- 17225446
TI  - [Non-Hodgkin's lymphomas of the digestive tract and anexal glands in AIDS
      patients].
AB  - BACKGROUND: Non-Hodgkin's lymphoma (NHL) is the second most common neoplasm among
      patients with AIDS. One of the major clinical characteristics of AIDS-associated
      NHL is the high frequency of extra-nodal involvement, including the
      gastrointestinal tract, at initial presentation. METHODS: From January 1997 to
      December 2004, 8 cases of NHL of the digestive tract and anexal glands (liver and
      parotid gland) were observed at the HIV/AIDS division of the Infectious Diseases
      FJ Muniz Hospital from Buenos Aires, Argentina. All patients were staged by
      computed tomography scanning and bone marrow examination, in addition to the
      endoscopic evaluation. RESULTS: All patients were males; 4 were heterosexual, 2
      homosexual, and 1 were a hemophilic and an intravenous drug abuser. The median
      age was 42 years and the median CD4 T cell count was 87 cells/uL at the time of
      the diagnosis of neoplasm. No patient was receiving highly active antiretroviral
      therapy (HAART) at lymphoma diagnosis. The global incidence of AIDS-associated
      lymphomas (central nervous system lymphomas, non-Hodgkin lymphomas and Hodgkin
      lymphoma) during the time of study was 2,9% (54 cases); 17 patients (32%) had
      diagnosis of systemic NHL; 10 (58,8%) of them were extranodal at the onset of
      clinical symptoms and 8 (80%) involvement the digestive tract and anexal glands
      (parotid gland, cavum, esophagus, stomach, duodenum, the right colon in 2
      patients and the liver), as primary NHL of high grade and "B" phenotype. All
      patients presented "B" symptoms at the time of diagnosis. Primary duodenal
      lymphoma was the only Burkitt lymphoma of this serie and we detected the Epstein
      Barr virus genome in the biopsy smears of this tumor and in the hepatic lymphoma.
      Four patients were treated with systemic chemotherapy with granulocitic growth
      factor support plus highly active antiretroviral therapy (HAART); 2 of them
      (cavum and one of the colon) had a prolonged survival with immune reconstitution
      during 5 and 6 years, respectively, after the diagnosis. The median survival of
      the patients, which received HAART plus chemotherapy, was 33 months. The median
      survival of the others patients was 90 days. CONCLUSION: NHL of the
      gastrointestinal tract is a severe complication of advanced HIV/AIDS disease.
      Early diagnosis followed by chemotherapy plus HAART are necessary to improve the
      prognosis and the survival of these patients.

PMID- 17225447
TI  - Celiac disease serology in dermatitis herpetiformis. Which is the best option for
      detecting gluten sensitivity?
AB  - BACKGROUND: Dermatitis herpetiformis (DH), a well-established gluten-sensitive
      skin disorder presenting variable degrees of enteropathy, constitutes a very
      useful model in order to assess the utility of the celiac disease (CD)-related
      serology in patients with mild intestinal damage. OBJECTIVE: Our aim was to
      explore comparatively the performance of a panel of CD-related serologic tests in
      patients with DH. METHODS: We assessed a series of 18 consecutive patients with
      skin biopsy proven DH presenting the overall spectrum of intestinal damage
      ranging from normal mucosa (n = 6) to total villous atrophy (TVA) (n = 6) through
      partial villous atrophy (PVA) (n = 6). Sera were obtained from all patients while
      consuming a gluten containing diet. Serologic tests were antiendomysial, anti
      tissue transglutaminase and antigliadin antibodies, and newly developed tests
      detecting both antibody isotypes (IgA and IgG) against deamidated synthetic
      gliadin-derived peptides (a-GDP). RESULTS: Serologic tests had a variable
      behaviour depending on the degree of enteropathy. While the majority of tests
      detected patients with TVA, only 50% of those with normal histology had positive
      assays. Patients with PVA had discordant results. Classical CD-specific tests
      were positive in only some patients with mild damage while all of them were
      identifed by a single assay detecting both isotypes of a-GDR CONCLUSION: The
      detection of a-GDP antibodies was the most reliable tool in order to identify
      gluten sensitivity in DH patients presenting a wide range of intestinal damage.
      Further studies should explore if these findings can be extrapolated to patients
      with CD having mild enteropathy.

PMID- 17225448
TI  - [Multiple splenic abscesses].
AB  - Multiple splenic abscesses is a rare condition in the clinical practice
      encountered mostly in immunocompromised patients. We report the case of a 81 year
      old male admitted to the hospital for fever, abdominal pain and jaundice. An
      abdominal ultrasound and computed tomography demonstrated multiple splenic
      abscesses. The splenectomy and antibiotics were a very effective therapy. The
      percutaneous drainage as an alternative may be appropriate only in selected
      patients, in order to preserve splenic function.

PMID- 17225449
TI  - ["Glassy - cell" like adenocarcinoma: a new variant of gastric tumor].
AB  - Most gastric malignancies correspond histologically to adenocarcinomas, either of
      the intestinal or diffuse type, other tumoral varieties being much less frequent.
      We report a case of a malignant epithelial tumor, whose histological and
      cytological characteristics correspond to an unusual, although well defined
      entity, which may appear in the cervix and less frequently in the endometrium,
      known as adenocarcinoma of the glassy - cell variety. We have not found any
      previous reports of this particular.

PMID- 17225451
TI  - [The treatment of anorexia-cachexia syndrome in cancer].

PMID- 17225450
TI  - [Apoptosis and progression of hepatic fibrosis in liver diseases].
AB  - Apoptosis is a Greek term that means "the fall of the old leaves of the autumn
      trees". This term describes the process by which undesirable, damaged or old
      cells are eliminated from the multicellular organisms. Pathologic cell death in
      the liver has traditionally been referred to as necrosis, but pathophysiologic
      process in the liver can lead to cell injury and death by apoptosis as well by
      necrosis. The first differs from the second, because it is actively controlled
      and the membrane integrity is maintained, avoiding extravasations of
      intracellular material and inflammatory response. Apoptosis can occur by two
      mechanisms: death receptor (DR) or extrinsic mechanism and mitochondrial or
      intrinsic mechanism. Liver cells express different death receptors: hepatocytes
      express Fas, TNF-R1, TRAIL-R1, TRAIL-R2; Stellate Cell (HCS) express Fas and
      TRAIL when is activated into myofibroblast-like phenotype and undergo apoptosis
      during resolution of liver injury in vivo. Cholangiocytes seem to be type II
      cells (in which the mitochondrial mechanism to apoptotic is essential) regarding
      signaling of Fas endothelial cells from rat livers express Fas, and their
      activation may lead to apoptosis of endothelial cells from hepatic sinusoids.
      Apoptosis mediated by these receptors have a major role in a variety of
      biological processes as tissue injury, protection against pathogenic
      microorganisms, and the role on hepatic injury and posterior progression to
      fibrosis has been well established in different hepatic diseases. Apoptosis may
      occur in the absence of significant transaminase elevations as happen in cellular
      necrosis. This paper is a review of this process.

PMID- 17225452
TI  - Platinum transporters and drug resistance.
AB  - Cisplatin, a platinum coordinated complex, is a widely used antineoplastic agent
      for the treatment of metastatic tumors of the testis, metastatic ovarian tumors,
      lung cancer, advanced bladder cancer and many other solid tumors. The cytotoxic
      action of the drug is often thought to be associated with its ability to bind DNA
      to form cisplatin-DNA adducts. The development of resistance to cisplatin during
      treatment is common and constitutes a major obstacle to the cure of sensitive
      tumors. Although to understand the clinically relevant mechanisms of resistance,
      many studies have been aimed at clarifying the biochemical/molecular alterations
      of cisplatin-resistance cells, these studies did not conclusively identify the
      basis of cellular resistance to cisplatin. In this review, cisplatin resistance
      was discussed in terms of the relevant transporters, such as copper transporters
      (CTRs), organic cation transporters (OCTs) and multi-drug resistance related
      transporters (MDRs). These transporters seem to be contributed to cisplatin
      resistance through the reduction of drug accumulation in the cell. Better
      understanding the mechanism of cisplatin resistance associated with transporters
      will provide the useful informations for overcoming the cisplatin resistance.

PMID- 17225453
TI  - In vitro peroxynitrite scavenging activity of 6-hydroxykynurenic acid and other
      flavonoids from Gingko biloba yellow leaves.
AB  - As part of our research on phytochemicals that exert protective effects against
      diseases related to reactive nitrogen species, we have evaluated the scavenging
      activity of the yellow leaves of Ginkgo biloba on ONOO-. The methanol extract and
      ethyl acetate fraction obtained from yellow leaves of G. biloba evidenced a
      marked scavenging activity on authentic ONOO-. Repeated column chromatography of
      the active ethyl acetate soluble fraction on silica gel, Sephadex LH-20, and RP
      18, resulted in the purification of 15 known compounds, including sciadopitysin
      (1), ginkgolide B (2), bilobalide (3), isoginkgetin (4), kaempferol (5), luteolin
      (6), protocatechuic acid (7), bilobetin (8), amentoflavone (9), beta-sitosterol
      glucopyranoside (10), kaempferol 3-O-rhamnopyranoside (11), kaempferol 3-O
      glucopyranoside (12), kaempferol 3-O-[6"'-O-p-coumaroyl-beta-D-glucopyranosyl(1 -
      > 2)-alpha-L-rhamnopyranoside] (13), kaempferol 3-O-rutinoside (14), and 6
      hydroxykynurenic acid (15). Among the compounds isolated, flavonoids (5, 6 and 11
      14), protocatechuic acid (7), and 6-hydroxykynurenic acid (15) all exhibited
      marked scavenging activities on authentic ONOO-. The IC50 values of 5-7, 11-14
      and 15 were as follows: 2.86 +/- 0.70, 2.30 +/- 0.04, 2.85 +/- 0.10, 5.60 +/-
      0.47, 4.16 +/- 1.65, 2.47 +/- 0.15, 3.02 +/- 0.48, and 6.24 +/- 0.27 microM,
      respectively. DL-Penicillamine (IC50 = 4.98 +/- 0.27 microM) was utilized as a
      positive control. However, the other compounds (1-4, 8-10) exerted no effects
      against ONOO-.

PMID- 17225454
TI  - Synthesis of 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-ones and
      evaluation of their anticonvulsant properties.
AB  - A series of 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-one
      derivatives were synthesized using 7-hydroxy-3,4-dihydro-2(1H)-quinolone as the
      starting material. Their anticonvulsant activities were evaluated by the maximal
      electroshock test (MES) and the subcutaneous pentylenetetrazole test (sc-PTZ),
      and their neurotoxicities were measured by the rotarod neurotoxicity test (Tox).
      The tests demonstrated that 8-hexyloxy-4,5-dihydro-[1.2.4]triazole[4.3
      a]quinoline-1-one (4e) and 8-heptyloxy-4,5-dihydro-[1,2,4] triazole[4,3
      a]quinoline-1-one (4f) were the most potent anticonvulsants, with 4e having ED50
      values of 17.17 mg/kg and 24.55 mg/kg and protective index (PI = TD50/ED50)
      values of 41.9 and 29.3 in the MES and sc-PTZ tests, respectively, and 4f having
      ED50 values of 19.7 mg/kg and 21.2 mg/kg and PI values of 36.5 and 33.9 in the
      MES and sc-PTZ tests, respectively. The PI values of 4e and 4f were many fold
      better than that of the marketed drugs phenytoin, carbamazepine, phenobarbital
      and valproate, which have PI values in the range of 1.6-8.1 in the MES test and <
      0.22-5.2 in the sc-PTZ test. Structure-activity relationships were also
      discussed.

PMID- 17225455
TI  - Cytotoxic phenolic constituents of Acer tegmentosum maxim.
AB  - The chromatographic separation of the MeOH extract from the twigs of Acer
      tegmentosum led to the isolation of ten phenolic compounds. The structures of
      these compounds were determined using spectroscopic methods as 3,7,3',4'
      tetramethyl-quercetin (1), 5,3'-dihydroxy-3,7,4'-trimethoxy flavone (2), 2,6
      dimethoxy-p-hydroquinone (3), (-)-catechin (4), morin-3-O-alpha-L-lyxoside (5), p
      hydroxy phenylethyl-O-beta-D-glucopyranoside (6), 3,5-dimethoxy-4-hydroxy phenyl
      1-O-beta-D-glucoside (7), fraxin (8), 3,5-dimethoxy-benzyl alcohol 4-O-beta-D
      glucopyranoside (9) and 4-(2,3-dihydroxy propyl)-2,6-dimethoxy phenyl beta-D
      glucopyranoside (10). The compounds were examined for their cytotoxic activity
      against five cancer cell lines. Compound 3 exhibited good cytotoxic activity
      against five human cancer cell lines with ED50 values ranging from 1.32 to 3.85
      microM.

PMID- 17225456
TI  - Synthesis, cytotoxicity and structure-activity relationship study of
      terpyridines.
AB  - For the development of novel antitumor agents, we designed and synthesized
      terpyridines, and their biological activities were evaluated. Although most of
      the newly prepared terpyridines showed strong cytotoxicity against several human
      cancer cell lines, [2,2';6',2"]-terpyridine displayed the most significant
      cytotoxicity.

PMID- 17225457
TI  - Prevention of epimerization and quantitative determination of amygdalin in
      Armeniacae Semen with Schizandrae Fructus solution.
AB  - Armeniacae Semen not only contains amygdalin, but emulsin also, which is an
      enzyme that hydrolyzes amygdalin. The extraction yield of amygdalin from
      Armeniacae Semen was low, due to the presence of emulsin, when extracted with
      water. When Schizandrae Fructus solution was used as the extractant; however,
      amygdalin was almost completely extracted, regardless of the cutting size, due to
      the absence of the influence of emulsin. In addition, when the crude powder or
      small piece forms were used with Schizandrae Fructus solution, on epimerization
      of the D-amygdalin into neoamygdalin occurred. D-amygdalin and its conversion
      product, neoamygdalin, were quantitatively analyzed by reverse-phase, high
      performance liquid chromatography (HPLC), with an optimized eluent of 10 mM
      sodium phosphate buffer (pH 2.3), containing 11.5% acetonitrile. The
      concentration and detector response were linearly correlated over the range 0.05
      to 2 mM. The detection limits for both D-amygdalin and neoamygdalin were
      approximately 5 microM for the amount injected.

PMID- 17225458
TI  - Anti-inflammatory activity of flavonoids from Populus davidiana.
AB  - An in vitro bioassay-guide revealed that the methanol (MeOH) extract of the stem
      bark of Populus davidiana showed considerable inhibitory activity against
      cyclooxygenase (COX-1, COX-2). Continuous phytochemical study of the MeOH extract
      of this plant led to the isolation of ten flavonoids; sakuranetin (1),
      rhamnocitrin (2), 7-O-methylaromadendrin (3), naringenin (4), eriodictyol (5),
      aromadendrin (6), kaempferol (7), neosakuranin (8), sakuranin (9) and sakurenetin
      5,4'-di-beta-D-glucopyranoside (10). Their structures were identified on the
      basis of their physicochemical and spectroscopic analyses. The isolated
      compounds, 1-10, were tested for their inhibitory activities against COX-1 and
      COX-2. Compound 7 was found to have potent inhibitory effect on COX-1 and a
      moderate effect on COX-2, meanwhile, compounds 1-6 showed moderate inhibition
      against COX-1 only. Moreover, compounds 5-8 exhibited suppressive effects on
      xanthine oxidase (XO). These results may explain, in part, the traditional uses
      of P. davidiana in ethnomedicine.

PMID- 17225459
TI  - A new furofuran lignan from Geranium thunbergii Sieb. et Zucc.
AB  - A new furofuran lignan, 4-hydroxykobusin (3), together with known lignans,
      kobusin (1), and 7,7'-dihydroxybursherenin (2), were isolated from the whole
      plant of Geranium thunbergii Sieb. et Zucc (Geraniaceae). The structures were
      determined based on the spectral data and a comparison with the published data.
      This is the first report of the presence of furofuran lignan in Geranium species.

PMID- 17225460
TI  - Effects of (+)-eudesmin from the stem bark of magnolia kobus DC. var. borealis
      Sarg. on neurite outgrowth in PC12 cells.
AB  - (+)-Eudesmin [4,8-bis(3,4-dimethoxyphenyl)-3,7-dioxabicyclo[3.3.0]octane] was
      isolated from the stem bark of Magnolia kobus DC. var. borealis Sarg. and found
      to have neuritogenic activity. 50 microM (+)-eudesmin induced neurite outgrowth
      and enhanced nerve growth factor (NGF)-mediated neurite outgrowth from PC12
      cells. At this concentration, (+)-eudesmin also enhanced NGF-induced neurite
      bearing activity and this activity was partially blocked by various protein
      kinase inhibitors. These included PD98059, a mitogen-activated protein kinase
      (MAPK) kinase inhibitor. GF109203X, a protein kinase C (PKC) inhibitor and H89, a
      protein kinase A (PKA) inhibitor. These results suggest that (+)-eudesmin can
      induce neurite outgrowth from PC12 cells by stimulating up-stream MAPK, PKC and
      PKA pathways.

PMID- 17225461
TI  - Monoamine oxidase inhibitory coumarins from the aerial parts of Dictamnus albus.
AB  - The methanol extract from the aerial parts of Dictamnus albus was active in
      inhibiting monoamine oxidase (MAO) from the mouse brain. Activity-guided
      fractionation led to the isolation of four known coumarins, 7-(6'R-hydroxy-3', 7'
      dimethyl-2'E, 7'-octadienyloxy) coumarin (1), auraptene (2), umbelliferone (3),
      and xanthotoxin (4), as active compounds along with an inactive alkaloid,
      skimmianine (5). Compounds 1 and 2 inhibited MAO activity in a concentration
      dependent manner with IC50 values of 0.7 and 1.7 microM, respectively. Compounds
      1 and 2 showed a slight and potently selective inhibitory effect against MAO-B
      (IC50 0.5 and 0.6 microM, respectively) compared to MAO-A (IC50 1.3 and 34.6
      microM, respectively). According to kinetic analyses derived by Lineweaver-Burk
      reciprocal plots, compounds 1 and 2 exhibited a competitive inhibition to MAO-B.

PMID- 17225462
TI  - Induction of apoptosis and transient increase of phosphorylated MAPKs by diallyl
      disulfide treatment in human nasopharyngeal carcinoma CNE2 cells.
AB  - This study was undertaken to elucidate the effect of diallyl disulfide (DADS), an
      oil-soluble organosulfur compound found in garlic, in suppressing human
      nasopharyngeal carcinoma cells. A potent increase (of at least 9-fold) in
      apoptotic cells has accompanied 1) a decrease in cell viability, 2) a increase of
      the fraction of S-phase cells by up to 63.8%, and 3) a transient increase of the
      phospho-p38 and phospho-p42/44 (phosphorylated p38 MAPK and phosphorylated p42/44
      MAPK) in a time- and concentration-dependent manner. These results indicate that
      DADS can induce apoptosis in human nasopharyngeal carcinoma cells via, at least
      partly, S-phase block of the cell cycle, related to a rise in MAPK
      phosphorylation.

PMID- 17225463
TI  - Analyses of single nucleotide polymorphisms and haplotype linkage of the human
      ABCB1 (MDR1) gene in Korean.
AB  - Single nucleotide polymorphisms (SNPs) in the MDR1 gene that are responsible for
      drug efflux can cause toxicity. Therefore, this study determined the SNPs of the
      Korean MDR1 gene, and analyzed the haplotypes and a linkage disequilibrium (LD)
      of the SNPs determined. The frequency of 9 SNPs from the MDR1 gene was determined
      by PCR-RFLP analyses of 100 to 500 healthy individuals. The frequcies of the SNPs
      were C3435T (47.7%), G2677T (37.6%), G2677A (4.4%), T1236C (21.7%), T129C (8%),
      A2956G (2.5%), T307C (1.5%), A41aG (9.2%), C145G (0%), and G4030C (0 %). Analyses
      of the haplotype structure and an estimation of the LD of the combined
      polymorphisms demonstrated that the frequency of the 1236T-2677G-3435T haplotype
      is much higher in Koreans (14.1%) than in Chinese and western black Africans and
      the C3435T SNP in Koreans appears to have LD with T129C in Koreans for the first
      time. These results provide insight into the genetic variation of MDR1 in
      Koreans, and demonstrated the possibility of a new LD in this gene.

PMID- 17225464
TI  - Induction of apoptotic cell death by a ceramide analog in PC-3 prostate cancer
      cells.
AB  - Ceramide analogs are potential chemotherapeutic agents. We report that a ceramide
      analog induces apoptosis in human prostate cancer cells. The ceramide analog
      induced cell death through an apoptotic mechanism, which was demonstrated by DNA
      fragmentation, the cleavage of poly ADP ribose polymerase (PARP), and a loss of
      membrane asymmetry. Treating the cells with ceramide analog resulted in the
      release of various proapoptotic mitochondrial proteins including cytochrome c and
      Smac/DIBLO into the cytosol, and a decrease in the mitochondrial membrane
      potential. In addition, the ceramide analog decreased the phospho-Akt and phospho
      Bad levels. The expression of the antiapoptotic Bcl-2 decreased slightly with
      increasing Bax to Bcl-2 ratio. These results suggest that the ceramide analog
      induces apoptosis by regulating multiple signaling pathways that involve the
      mitochondrial pathway.

PMID- 17225466
TI  - ErmK leader peptide : amino acid sequence critical for induction by erythromycin.
AB  - The ermK gene from Bacillus lichenformis encodes an inducible rRNA methylase that
      confers resistance to the macrolide-lincosamide-streptogramin B antibiotics. The
      ermK mRNA leader sequence has a total length of 357 nucleotides and encodes a 14
      amino acid leader peptide together with its ribosome binding site. The secondary
      structure of ermK leader mRNA and a leader peptide sequence have been reported as
      the elements that control expression. In this study, the contribution of specific
      leader peptide amino acid residues to induction of ermK was studied using the PCR
      based megaprimer mutation method. ermK methylases with altered leader peptide
      codons were translationally fused to E. coil beta-galactosidase reporter gene.
      The deletion of the codons for Thr-2 through Ser-4 reduced inducibility by
      erythromycin, whereas that for Thr-2 and His-3 was not. The replacement of the
      individual codons for Ser-4, Met-5 and Arg-6 with termination codon led to loss
      of inducibility, but stop mutation of codon Phe-9 restored inducibility by
      erythromycin. Collectively, these findings suggest that the codons for residue 4,
      5 and 6 comprise the critical region for induction. The stop mutation at Leu-7
      expressed constitutively ermK gene. Thus, ribosome stalling at codon 7 appears to
      be important for ermK induction.

PMID- 17225465
TI  - Effects of mizoribine on MHC-restricted exogenous antigen presentation in
      dendritic cells.
AB  - Mizoribine (MZR) has been shown to possess immunosuppressive activity that
      selectively inhibits the proliferation of lymphocytes by interfering with inosine
      monophosphate dehydrogenase. The efficacy of MZR is not only in patients who have
      had renal transplantation, but also in patients with rheumatoid arthritis (RA),
      lupus nephritis, and primary nephritic syndrome. Because the exact mechanism of
      its immunosuppressive action is not clear, the object of this study was to
      examine the ability of MZR to regulate the antigen presenting cells (APCs),
      dendritic cells (DCs). In this work, we tested whether MZR (1-10 microg/mL) could
      inhibit the cross-presentation of DCs. DC2.4 cells (H-2K(b)) or bone marrow
      derived DCs (BM-DCs) generated from BM cells of C57BL/6 mouse (H-2K(b)) were
      cultured in the presence of MZR with OVA-microspheres, and the amount of OVA
      peptide-class I MHC complexes was measured by a T cell hybridoma, B3Z, that
      recognizes OVA (257-264 : SIINFEKL)-H-2Kb complex and expresses-galactosidase.
      MZR profoundly inhibited the expression of SIINFEKL-H-2K(b) complexes. This
      inhibitory activity of MZR appeared to affect the phagocytic activity of DCs. MZR
      also decreased IL-2 production when we examined the effects of MZR on CD4+ T
      cells. These results provide an understanding of the mechanism of
      immunosuppressive activity of MZR on the inhibition of MHC-restricted antigen
      presentation and phagocytic activity in relation to their actions on APCs.

PMID- 17225467
TI  - In vivo effects of lead on erythrocytes following chronic exposure through
      drinking water.
AB  - More than 95% of lead, a environmental heavy metal, entering into blood
      accumulates in erythrocytes suggesting erythrocytes as an important target of
      lead toxicity. Recent studies reported that erythrocytes could contribute to
      blood coagulation via phosphatidylserine (PS) exposure in erythrocytes. However,
      in vivo effects of chronic lead exposure especially by drinking water on
      procoagulant activity of erythrocytes have not been studied yet. In the present
      study, we investigated the effects of chronic exposure of lead by drinking water
      on erythrocytes in rats. Groups of 40 male rats were provided with drinking water
      containing various concentrations of lead for 4 weeks and complete blood cell
      count, procoagulant activities of erythrocytes and platelets were evaluated with
      basic inspections on body weight and food/ water consumption. The administration
      of lead containing drinking water increased the blood lead level (BLL) in a dose
      dependent manner up to 22.39 +/- 2.26 microg/dL. Water consumption was
      significantly decreased while food consumption or body weight gain was not
      affected. In contrast to the "previous findings with acute lead exposure, chronic
      lead exposure failed to increase PS exposure in erythrocytes with statistical
      significance although some trends of enhancement were observed. It implies that a
      certain adaptation might have happened in body during repeated exposure to lead,
      resulting in attenuation of PS exposure. With this study, we believe that a
      valuable information was provided for the study on the toxicological significance
      and the risk assessment of lead contaminated drinking water.

PMID- 17225469
TI  - Effect of flavors on the viscosity and gelling point of aqueous poloxamer
      solution.
AB  - This study examined the effects of flavors, which are usually added to improve
      the appeal of pharmaceutical agents, on the viscosity and gelling point of 18%
      (w/w) aqueous poloxamer 407 solutions. Monoterpenes, esters, alcohols, aldehyde .
      ketones and lactone type flavors were examined. The concentrations of flavor
      ranged from 0.1 to 1.0% (w/w). After adding a flavor to the aqueous poloxamer 407
      solution, the viscosity of the solution was measured using a Brookfield
      viscometer, and the gelling point was determined from the viscosity vs.
      temperature plot. The gelling point of the aqueous poloxamer 407 solution
      decreased with increasing concentration of flavors except for coumarin, vanillin
      and ethylvanillin. Thermal analysis with DSC showed an interaction between the
      flavors and poloxamer 407. These results suggest that the flavors bind to the
      hydrophilic end chains of poloxamer 407, which increases the viscosity, causing
      gelation at lower temperatures.

PMID- 17225468
TI  - Synthesis, characterization and in vitro evaluation of triptolide-lysozyme
      conjugate for renal targeting delivery of triptolide.
AB  - A triptolide-lysozyme (TP-LZM) conjugate was synthesized to achieve renal
      specific delivery and to reduce the side effects of triptolide. Triptolide was
      coupled to lysozyme through succinic via an ester bond with an average coupling
      degree of 1 mol triptolide per 1 mol lysozyme. The lysozyme can specifically
      accumulate in the proximal tubular cells of the kidney, making it a potential
      carrier for targeting drugs to the kidney. The structure of triptolide succinate
      (TPS) was confirmed by IR, 1H-NMR, MS and UV. The concentrations of triptolide in
      various samples were determined by reversed-phase high-performance liquid
      chromatography (HPLC). In this study, the physicochemical and stability profiles
      of TP-LZM under various conditions were investgated the stability and releasing
      profiles of triptolide-lysozyme (TP-LZM) under various conditions. In vitro
      release trails showed triptolide-lysozyme was relatively stable in plasma (less
      than 30% of free triptolide released) and could release triptolide quickly in
      lysosome (more than 80% of free triptolide released) at 37 degrees C for 24 h. In
      addition, the biological activities of the conjugate on normal rat kidney
      proximal tubular cells (NRK52E) were also tested. The conjugate can effectively
      reduce NO production in the medium of NRK52E induced by lipopolysaccharide (LPS)
      but with much lower toxicity. These studies suggest the possibility to promote
      curative effect and reduce its extra-renal toxicity of triptolide by TP-LZM
      conjugate.

PMID- 17225470
TI  - Cross-linked starch microspheres: effect of cross-linking condition on the
      microsphere characteristics.
AB  - Cross-linked starch microspheres were prepared using different kinds of cross
      linking agents. The influence of several parameters on morphology, size, swelling
      ratio and drug release rate from these microspheres were evaluated. These
      parameters included cross-linker type, concentration and the duration of cross
      linking reaction. Microspheres cross-linked with glutaraldehyde had smooth
      surface compared with those prepared with epichlorhydrine or formaldehyde. The
      particle size increased with increasing the cross-linking time and increasing the
      drug loading. Swelling ratio of the particles was a function of cross-linker type
      but not the concentration or time of cross-linking. Drug release from starch
      microspheres was measured in phosphate buffer and also in phosphate buffer
      containing alpha-amylase. Results showed that microspheres cross-linked with
      epichlorhydrine released all their drug content in the first 30 minutes. However,
      cross-linking of the starch microspheres with glutaraldehyde or formaldehyde
      decreased drug release rate. SEM and drug release studies showed that cross
      linked starch microspheres were susceptible to the enzymatic degradation under
      the influence of alpha-amylase. Changing the enzyme concentration from 5000 to
      10,000 IU/L, increased drug release rate but higher concentration of enzyme
      (20,000 IU/L) caused no more acceleration.

PMID- 17225472
TI  - Cancer's orphan generation. Medical experts increase the survival rates of teens
      and young adults.

PMID- 17225471
TI  - Formulation of liposome for topical delivery of arbutin.
AB  - The aims of this study were to encapsulate arbutin (AR) in liposome to enhance
      the skin-whitening activity, and to investigate the effect of liposome
      formulation on the entrapment efficiency (EE%), skin permeation rate and skin
      deposition. The liposomes were prepared by a film dispersion method with several
      different formulations and were separated from the solution by using the gel
      filtration method. The physical (size distribution, morphology) and chemical
      (drug entrapment efficiency, hairless mouse skin permeation and deposition)
      properties of liposomes were characterized. The entrapment efficiency in all
      liposome formulations varied between 4.35% and 17.63%, and was dependent on the
      lipid content. The particle sizes of liposomes were in the range of 179.9-212.8
      nm in all liposome formulations. Although the permeation rate of AR in the
      liposome formulations decreased compared with AR solution, the deposition amount
      of AR in the epidermis/dermis layers increased in AR liposomal formulation. These
      results suggest that liposomal formulation could enhance the skin deposition of
      hydrophilic skin-whitening agents, thereby enhancing their activities.

PMID- 17225473
TI  - Screening for all. New guidelines urge every pregnant woman to get early testing
      for risk of Down syndrome.

PMID- 17225474
TI  - Autism's many meanings. A child's culture will affect how he's treated.

PMID- 17225475
TI  - Space cycle: a human-powered centrifuge that can be used for hypergravity
      resistance training.
AB  - INTRODUCTION: This study represents the first step toward testing the hypothesis
      that hypergravity can be used as a unique resistance training modality for
      maintaining the health and function of skeletal muscle in microgravity. The
      primary objectives of this study were to use a human-powered short-arm centrifuge
      for the following: 1) to determine whether subjects could perform squats under
      hypergravity conditions without developing motion sickness or illusory motion; 2)
      to measure foot forces while performing squats under hypergravity conditions; and
      3) to determine the mechanical power required to produce 1.5, 2.0, 2.5, and 3.0
      Gz (head to foot) at the feet. METHODS: Subjects (22 males and 19 females)
      performed 10 squats each at 1.5, 2.0, 2.5, and 3.0 Gz on a human-powered short
      arm centrifuge, the space cycle. Foot forces during each squat were monitored
      using insole force sensors, and normalized to foot forces measured at 1 Gz
      (relative foot forces). RESULTS: Illusory motion was minimized using a visual
      focal point, and did not affect the ability of subjects to perform squats. The
      mean standing relative foot forces at 3.0 Gz were 2.3 and 2.4 for the male and
      female subjects, respectively. The work rate required to power the space cycle
      was a linear function of Gz, and is well within the aerobic scope of untrained
      individuals. DISCUSSION: The findings of this study demonstrate that hypergravity
      can be used as an effective modality for loading skeletal muscle and that
      subjects can perform squat resistance exercise without developing motion sickness
      or illusory motion.

PMID- 17225476
TI  - Cognitive performance following premature awakening from zolpidem or melatonin
      induced daytime sleep.
AB  - BACKGROUND: The hypnotic zolpidem and the hormone melatonin were evaluated and
      directly compared for their effects on performance when subjects sleeping under
      their influence were prematurely awakened from daytime sleep. METHOD: Non-sleep
      deprived volunteers (eight men and five women) received single oral doses of 5 or
      10 mg melatonin (Mel-5; Mel-10), 10 or 20 mg zolpidem (Zol-10; Zol-20), or
      placebo immediately before retiring at 13:00. Performance testing and subjective
      evaluations occurred prior to dosing and following forced awakening at 15:00, 2 h
      after dosing. RESULTS: Compared with placebo, on being awakened under Zol-20,
      significant performance decrements were prevalent on 9 of 10 cognitive tasks,
      including grammatical reasoning, mathematical processing, and word memory.
      Recovery required up to 6 h post-awakening for the more complex tasks. Loss of
      coordination and nausea were also present on awakening under Zol-20. On being
      awakened under Zol-10, significant but relatively less severe and shorter
      duration performance decrements occurred for 4 of the 10 tasks and recovered by 4
      h post-awakening. Under Mel-5 or Mel-10, performance decrements seldom occurred
      and were considerably less severe, briefer, and less systematic than for
      zolpidem. CONCLUSION: Findings indicated that when operational personnel sleeping
      with the aid of either 10 or 20 mg zolpidem are prematurely awakened, it would be
      prudent to evaluate their general well-being and possible need for assistance
      prior to their being permitted to depart crew-rest or to perform tasks and
      duties. In contrast, we found little to no evidence of deteriorated well-being or
      need for assistance when awakened while sleeping under the influence of
      melatonin.

PMID- 17225477
TI  - Can color vision defective subjects who pass the farnsworth lantern test
      recognize surface color codes?
AB  - INTRODUCTION: The International Civil Aviation Organization requires that pilots
      be able to distinguish the colors used in air navigation and in particular be
      able to identify the colors of signal lights. Most national aviation authorities
      use a lantern test to assess the ability of applicants for a pilot's license who
      have abnormal color vision to recognize the colors of signal lights. However,
      color-coding is now widely used in aviation systems other than signal lights.
      Color is used in tarmac markings, maps, manuals, and electronic flight instrument
      displays. These color codes can use 10 or more colors, many more than the 3 to 5
      used for signal lights. This study investigated whether people with defective
      color vision (DCV) who pass the Farnsworth lantern test can recognize the main
      colors used for surface color codes. METHODS: There were 99 subjects with DCV who
      were tested using the Optec 900 version of the Farnsworth lantern test and also
      named the colors of a set of 10 surface colors that varied in shape (dots and
      lines) and size (3 sizes; angular diameters 0.27, 1.0, and 2.4 degrees; angular
      widths 0.14, 0.27, and 0.50 degrees). A control group of 20 subjects with normal
      color vision also named the surface colors. RESULTS: Of the DCV subjects, 19%
      passed the Farnsworth lantern test, of whom 74% made no errors with the surface
      colors. The other 26% made few errors (up to 5 errors in 120 presentations) and
      those errors were mostly to confuse red, orange, and brown. The subjects with
      normal color vision made no errors naming the surface colors. CONCLUSION: Those
      who pass the Farnsworth lantern test can recognize the colors of a 10-color
      surface color code with few or no errors. This is because the small (2.9-min arc)
      stimulus of the lantern test presents a more difficult task than the larger
      surface colors.

PMID- 17225478
TI  - Glider accidents: an analysis of 143 cases, 2001-2005.
AB  - INTRODUCTION: The majority of aviation crashes and casualties take place in
      general and sport aviation. Although gliding has gained popularity in recent
      decades, we could find no systematic analysis of glider accidents. This study
      determined factors associated with both non-fatal and fatal glider accidents to
      document their position within sport and general aviation accidents, and to
      suggest preventive measures and improvements. METHODS: We performed a
      retrospective review of glider accidents for the period 2001-2005 in the database
      maintained by the U.S. National Transportation Safety Board (NTSB). RESULTS: A
      total of 117 non-fatal and 26 fatal glider accidents were reported for the 5-yr
      period. Adverse weather was the cause in 20% of all non-fatal accidents, 60% of
      which occurred in the cruise phase. Logistic regression revealed that fatal
      accidents were predicted by pilot error, flight phase, and home-built aircraft.
      DISCUSSION: Factors contributing to glider crashes are specific to this type of
      sport aviation. Owners of home-built gliders should pay particular attention to
      the aircraft's specifications and design limits.

PMID- 17225479
TI  - Atopic dermatitis: diagnosis, treatment, and aeromedical implications.
AB  - Over the past 30 yr, the prevalence of atopic dermatitis (AD) has increased
      significantly in the general population. Given this increased burden of disease,
      more AD will be seen in civilian and military aviators. This article reviews the
      clinical aspects of AD with a focus on the aeromedical implications of the
      disease. The diagnosis of AD is mainly clinical. Treatment options are numerous,
      although topical corticosteroids are generally the mainstay of treatment. The new
      immunomodulators are options for treatment of AD and have advantages and
      disadvantages when compared with topical corticosteroids. These immunomodulators
      are discussed in detail with an emphasis on their mechanism of action, efficacy,
      side effect profile, and possible risks. The implications of AD in aviators and
      safety of flight are reviewed. Interference of the wearing of cockpit equipment,
      use of systemic or topical medications, and AD's association with the other
      diseases of atopy all contribute to whether an aviator is qualified to fly.
      Environmental triggers, such as temperature changes, sweating, humidity, bathing
      frequency, contact with irritating substances, and stress may exacerbate the
      aviator's disease. Special consideration should be given to the severity of their
      disease, the treatment the aviator requires, and the environment he or she will
      be working and living in before giving aeromedical clearance. Finally, the
      policies of each military service and experiences in civil aviation are
      discussed.

PMID- 17225480
TI  - Head position of helicopter pilots during slalom maneuvers.
AB  - INTRODUCTION: Pilots typically tilt their heads when executing coordinated
      banking turns, a phenomenon commonly attributed to the putative opto-kinetic
      cervical reflex (OKCR). The OKCR is usually described as a reflex, primarily
      driven by stimuli in the visual periphery, and is important to a pilot's spatial
      orientation by providing a relatively stabilized horizontal frame of reference.
      The present paper presents an alternative hypothesis for the observed head
      tilting seen in pilots. METHODS: An archived data set, originally collected for
      other purposes, contained the head turn, pitch, and tilt of 4 helicopter pilots
      recorded at 10 Hz as the pilots executed 42 slalom maneuvers in an AH Mk 7 Lynx
      helicopter under visual flight conditions. The analytic method was a
      correlational analysis of head turn, pitch, and tilt. RESULTS: As expected,
      pilots routinely tilted their heads during the slaloms in a fashion typically
      attributed to the OKCR. Correlations among head turn, tilt, and pitch showed that
      when the helicopter turned left, the head, presumably to look into the turn,
      turned left and also pitched up and tilted right. Similarly, when the helicopter
      turned right, the head, presumably to look into the turn, turned right, pitched
      up, and tilted left. CONCLUSIONS: The head tilting usually attributed to a
      neuromuscular reflex driven by visual stimuli may be a biomechanical consequence
      of the head posture pilots assume when they simply look where they are going,
      eliminating the need to postulate the existence of a novel neuromuscular reflex.

PMID- 17225481
TI  - Avian flight without visual reference: preflight spinning produces spatial
      disorientation.
AB  - INTRODUCTION: Birds regularly fly in conditions of reduced visibility where they
      cannot see the horizon, whereas human pilots under similar conditions are subject
      to spatial disorientation (SD) and must, therefore, rely on instruments to
      maintain safe flight. We surmised that pigeons whose eyes were covered and that
      were rotated in a centrifuge before flight might show signs of SD. METHODS: We
      built a small centrifuge ("ornifuge") that allowed us to spin a bird around the
      vertical axis of its head at 1 cps for a specified number of turns and then
      release it instantly through a trap bottom to fly free. We studied 67 cull racing
      pigeons once each under four conditions: 1) static with normal vision (Static
      See, n = 13); 2) static with eyes covered (Static-Cover, n = 17); 3) spin with
      normal vision (Spin-See, n = 15); and 4) spin with eyes covered (Spin-Cover, n =
      22). Flight behavior immediately on release was observed by the investigators and
      photographed to document the occurrence of initial hovering, direction of
      spontaneous rotation if any, and staggering after landing. Birds released with
      eye-covers flicked them off within a few moments. RESULTS: Both Static-See and
      Static-Cover birds flew normally. For Spin-See, most flew normally, but 27%
      hovered momentarily before flying away. Among Spin-Cover birds, abnormal flight
      was seen in 50% and 72% staggered after landing. DISCUSSION: Spinning in the
      ornifuge produced abnormal flight behavior in the majority of blind-folded birds.
      This may provide a model for examining certain aspects of SD experienced by
      pilots under instrument meteorological conditions and studying the mechanisms
      that make birds relatively resistant to SD.

PMID- 17225483
TI  - B-type natriuretic peptide in healthy subjects after exposure to hyperbaric
      oxygen at 2.5 ATA.
AB  - INTRODUCTION: B-type natriuretic peptide (BNP) is a cardiac hormone used as a
      marker of cardiac dysfunction with diuretic and vasodilating properties secreted
      by the ventricles in response to wall stress. Hyperbaric oxygen (HBO) exposure is
      known to induce hemodynamic effects in humans which can be complicated by acute
      pulmonary edema. The aim of this study was to investigate if HBO has any effects
      on the secretion of BNP in healthy human subjects. METHODS: Eight healthy
      volunteers underwent the following HBO protocol in a hyperbaric chamber:
      compression to 2.5 atmospheres absolute (ATA); 45 min breathing 100% oxygen; 5
      min breathing air; another 45 min in 100% oxygen; then decompression to
      atmospheric pressure. A venous blood sample was drawn before entering the chamber
      (To), immediately at the end of the treatment (T1), and at 5 h from To (T2). BNP
      concentration was determined using a rapid point-of-care immunoassay. Non
      parametric statistics were used to analyze data. RESULTS: No difference in BNP
      levels was found between T0 and T1 or T2. DISCUSSION: The findings of this
      preliminary study show that in healthy subjects a single HBO exposure does not
      significantly modify BNP plasma levels. We hypothesize that this can be the net
      result between the stimulating effect of the HBO-induced vasoconstriction and the
      direct inhibitory effect on BNP secretion of myocyte hyperoxia. We conclude that
      HBO does not modify BNP secretion in healthy volunteers and that the direct
      effect of extreme hyperoxia on BNP secretion deserves further investigation.

PMID- 17225482
TI  - Alcohol screening instruments and psychiatric evaluation outcomes in military
      aviation personnel.
AB  - INTRODUCTION: Alcohol-related disorders are the most prevalent psychiatric
      conditions in the aviation population. Efforts to effectively screen aviators for
      these disorders are continually sought, as underdiagnosis may negatively impact
      aviation safety. This study evaluates screening tools that have been validated in
      non-aviators in terms of their utility for aviator patients. METHODS: There were
      111 male aviation patients (27 +/- 7 yr) referred for psychiatric evaluation at
      the Naval Aerospace Medicine Institute who completed the Self-Administered
      Alcohol Screening Test (SAAST), the Alcohol-Use Disorders Identification Test
      (AUDIT), and the Common Alcohol Logistical Scale-Revised (CAL-R) prior to
      evaluation by a staff psychiatrist or psychologist. RESULTS: There were 40
      patients who were qualified psychiatrically with no diagnosis and 49 patients who
      were disqualified for psychiatric reasons due to a non alcohol-related diagnosis.
      The remaining 22 patients were disqualified for psychiatric reasons with an
      alcohol-related diagnosis. The optimal aviator cut-off scores were consistent
      with those of the general population, although the cut-off score used for the
      SAAST was set at the published sub-threshold level to provide greater
      sensitivity. The sensitivity/specificity values for the SAAST, AUDIT, and CAL-R
      were 59%/94%, 46%/96%, and 68%/81%, respectively. CONCLUSION: The
      psychometrically sophisticated CAL-R is sensitive, specific, and has good
      negative predictive value, although its use requires a psychologist and its
      availability is limited. The SAAST and AUDIT can be administered by a flight
      surgeon or aviation medical examiner (AME). Given the higher sensitivity of the
      SAAST it may be the most beneficial if administered first. The AUDIT can be used
      as a follow-up diagnostic test given its higher specificity.

PMID- 17225484
TI  - Ejection experience 1956-2004 in Japan: an epidemiological study.
AB  - BACKGROUND: Ejection injuries and fatalities are a problem around the world.
      However, the definitions of injury types in past studies have been idiosyncratic,
      and it has been difficult to compare studies across national air forces and
      aircraft types. This study determined factors that contribute to injury or
      fatality in ejections in the Japan Air Self Defense Force (JASDF). METHODS: The
      records for all JASDF ejections for the period 1956-2004 were analyzed to
      determine the relationships between types of injuries and ejection
      characteristics. RESULTS: There were 140 cases, of which 32 (22.9%) induced fatal
      injuries, 13 (9.3%) major injuries, and 95 (67.9%) no injuries. This fatality
      rate of nearly 23% is the highest found in similar studies. The most significant
      reason for fatality was the delay in the decision to eject, accounting for
      approximately 40%. This tendency to delay the decision to eject was observed
      across all of the time periods studied. Fuel exhaustion due to changeable weather
      was cited as a reason for ejecting at a higher rate than in other countries.
      CONCLUSIONS: Delay in the decision to eject was the most significant problem
      affecting ejection survival in Japan and was constant over time.

PMID- 17225485
TI  - Visual conversion disorder in a harbor pilot leading to sudden loss of control of
      a large vessel.
AB  - We describe an accident caused by the rapid onset of visual impairment in a
      ship's pilot, who was subsequently diagnosed as having visual conversion disorder
      (hysterical blindness). This case is documented to draw attention to the unusual
      cause of sudden incapacitation in transport crew and the consequential threat to
      transportation safety. Because sudden visual impairment incidents caused by
      conversion disorder are isolated and rare, they may be under-reported in the
      scientific literature. While it is unlikely that current systems for medical
      screening could anticipate and/or prevent crew incapacitation due to conversion
      disorders, this condition should be borne in mind when consulted by crew who
      report otherwise unexplained physical symptoms in the context of high levels of
      personal stress. It should also be considered when investigating possible medical
      incapacitation in transportation incidents or accidents.

PMID- 17225486
TI  - Rheumatoid arthritis in a military aviator.
AB  - Rheumatoid arthritis is a chronic inflammatory condition whose pathogenesis is
      determined partially by genetic and environmental factors. Without treatment, 20
      to 30% of individuals with this condition will become permanently disabled in a
      few years. Rheumatoid arthritis and its potential complications can cause
      significant disability and could seriously affect the performance of an aviator.
      Traditionally, disease-modifying anti-rheumatic drugs (DMARD) and biologics have
      not been used until disease progression occurs, but they recently have been added
      earlier in the course of disease for a more aggressive approach to treatment. It
      has been shown to significantly reduce the number of affected joints, pain, and
      disability. This newer treatment regimen has helped a military pilot continue his
      aviation career. We present the case of an experienced designated military pilot
      who was diagnosed with rheumatoid arthritis. He was initially treated early with
      a DMARD and biologic medication. He has remained in remission and currently only
      uses etanercept (biologic medication) and a non-steriodal anti-inflammatory drug
      to control his disease. He has responded favorably to therapy and has few
      limitations. Due to his positive response to treatment, the aviator was granted
      military aeromedical waivers for rheumatoid arthritis and chronic medication use.

PMID- 17225487
TI  - Thymic carcinoma.
AB  - This is a case of thymic carcinoma-a rare and highly aggressive type of tumor
      found in the anterior mediastinum. During a routine chest X-ray, a 66-yr-old male
      pilot was found to have a mediastinal mass. After diagnosis, he underwent
      chemotherapy, surgery, and radiation therapy and 1 yr after completion of these
      therapies he was re-issued a third-class medical certificate to fly.

PMID- 17225488
TI  - This month in aerospace medicine history--January 2007.

PMID- 17225489
TI  - Microarray applications in aerospace medicine.

PMID- 17225491
TI  - Brushing up on coverage value--"reducing the exposure to injuries by putting
      value into procedures and practices".

PMID- 17225490
TI  - Increase your treatment acceptance with one simple step.

PMID- 17225492
TI  - Accounts receivable "self analysis" by asking intelligent collections questions.

PMID- 17225493
TI  - Getting started: the process of a start-up practice.

PMID- 17225494
TI  - Remembering September 11, 2001.

PMID- 17225495
TI  - Oral pathology quiz # 53. Case number 1. Adult gingival cyst.

PMID- 17225496
TI  - Health: the British paradox.

PMID- 17225497
TI  - You too, can give the gift of life.

PMID- 17225498
TI  - Processing of dental instruments--are you following the correct procedures to
      ensure that your instruments are safe for patient treatment?--part II.

PMID- 17225499
TI  - Localized severe periodontitis associated with retained impression material and
      root proximity: report of a case.

PMID- 17225500
TI  - Medical quick reference glossary for dental clinicians: liver disease management
      issues.

PMID- 17225501
TI  - Office buildings. Social sustainability. Department of Health Services office
      building, Richmond, California.

PMID- 17225502
TI  - Predictability of locomotion: effects on updating of spatial situation models
      during narrative comprehension.
AB  - We investigated how the updating of spatial situation models during narrative
      comprehension depends on the interaction of cognitive abilities and text
      characteristics. Participants with low verbal and visuospatial abilities and
      participants with high abilities read narratives in which the protagonist's
      motions in a fictitious building were either highly predictable or very hard to
      predict. In Experiment 1, high-ability readers updated spatial situation models
      only if the protagonist's motions were hard to predict, whereas low-ability
      readers did so only if the motions were highly predictable. In Experiment 2,
      facilitated integrative spatial processing compensated for the low-ability
      participants' resource limitations. As a result, both ability groups updated
      spatial situation models with hard-to-predict protagonist motions. These results
      highlight the interactions of cognitive abilities and text characteristics in
      spatial situation model updating.

PMID- 17225503
TI  - Character movement and the representation of space during narrative
      comprehension.
AB  - Traditional research on situation models has examined the accessibility of
      locations and objects during narrative experiences. These studies have described
      a ubiquitous gradient effect: Spatial locations and objects in reader focus are
      more accessible than locations farther from this focus, with accessibility
      decreasing as a function of distance. How might readers' expectations about
      character movement, beyond information about spatial locations, additionally
      affect this accessibility gradient? In two experiments, we investigated whether
      reader expectations for character movement impact the accessibility of spatial
      information from memory. In Experiment 1, participants read stories that
      described characters moving in either a unidirectional or a random pattern
      through a learned environment. In Experiment 2, characters moved forward in a
      unidirectional way or backtracked through previously explored rooms. The results
      suggest that reader expectations for character movement can influence the
      accessibility of spatial information. Such expectations play a critical role in
      processes of narrative comprehension.

PMID- 17225504
TI  - Making sense of abstract events: building event schemas.
AB  - Everyday events, such as making a bed, can be segmented hierarchically, with the
      coarse level characterized by changes in the actor's goals and the fine level by
      subgoals (Zacks, Tversky, & Iyer, 2001). Does hierarchical event perception
      depend on knowledge of actors' intentions? This question was addressed by asking
      participants to segment films of abstract, schematic events. Films were novel or
      familiarized, viewed forward or backward, and simultaneously described or not.
      The participants interpreted familiar films as more intentional than novel films
      and forward films as more intentional than backward films. Regardless of
      experience and film direction, however, the participants identified similar event
      boundaries and organized them hierarchically. An analysis of the movements in
      each frame revealed that event segments corresponded to bursts of change in
      movement features, with greater bursts for coarse than for fine units. Perceiving
      event structure appears to enable event schemas, rather than resulting from them.

PMID- 17225505
TI  - Planning and task management in older adults: cooking breakfast.
AB  - The article describes a simulated "cooking breakfast" task in which participants
      must remember to start and stop cooking five foods so that all the foods are
      "ready" at the same time. In between starting and stopping operations, the
      participants also carried out a "table-setting" task as a filler activity. The
      breakfast task yields various measures of multitasking and executive control.
      Groups of younger and older adults performed the task; half of the participants
      in each group were bilinguals and the other half were monolinguals. The results
      showed substantial age-related decrements in most measures of executive control.
      Additionally, older bilinguals showed some advantages in task management over
      their monolingual peers.

PMID- 17225506
TI  - Priming or executive control? Associative priming of cue encoding increases
      "switch costs" in the explicit task-cuing procedure.
AB  - The explicit task-cuing procedure involves presenting a cue that indicates which
      task to perform on a target. Responses are typically faster when tasks repeat
      than when they alternate, and this difference is often interpreted as a measure
      of the time required for executive control processes to change task set. This
      article suggests that the difference reflects priming of cue encoding when
      successive cues are identical or associatively related. Subjects responded to
      task repetitions more quickly when the cue on the current trial was associatively
      related to the cue on the previous trial (e.g., day --> night) than when the cues
      were unrelated (e.g., verb --> night). Models applied to the time course function
      -generated by manipulating the interval between the onsets of the cue and the
      target--showed that the facilitation was due to cue encoding, a process that does
      not require online executive control.

PMID- 17225507
TI  - Accounting for sequential trial effects in the flanker task: conflict adaptation
      or associative priming?
AB  - The conflict-control loop theory proposes that the detection of conflict in
      information processing triggers an increase in cognitive control, resulting in
      improved performance on the subsequent trial. This theory seems consistent with
      the robust finding that conflict susceptibility is reduced following correct
      trials associated with high conflict: the conflict adaptation effect. However,
      despite providing favorable conditions for eliciting and detecting conflict
      triggered performance adjustments, none of the five experiments reported here
      provide unequivocal evidence of such adjustments. Instead, the results
      corroborate and extend earlier findings by demonstrating that the conflict
      adaptation effect, at least in the flanker task, is only present for a specific
      subset of trial sequences that is characterized by a response repetition. This
      pattern of results provides strong evidence that the conflict adaptation effect
      reflects associative stimulus-response priming instead of conflict-driven
      adaptations in cognitive control.

PMID- 17225508
TI  - Effects of repetition on memory for pragmatic inferences.
AB  - Social interaction requires active inferential processing on the part of the
      listener. Such inferences can affect memory. For example, after hearing the
      karate champion hit the cinder block, one might erroneously recollect having
      heard the verb broke (Brewer, 1977)--a reasonable inference, but one not
      logically necessitated. The mechanisms behind this type of erroneous recollection
      have not been much explored. Experiments in the present article assessed the
      influence of repetition, response deadline, and age (cf. Jacoby, 1999), in an
      effort to demonstrate the dual contributions of familiarity and recollection
      underlying this phenomenon. For older adults, repetition at encoding increased
      the later likelihood of erroneously recognizing pragmatic inferences. For younger
      adults, repetition exerted the opposite effect. Both age groups, however,
      benefited from a second study-test trial. Experiment 2 demonstrated a similar
      interaction on a cued recall test for younger adults, whereby repetition exerted
      different influences as a function of time permitted during retrieval.
      Implications for theories of memory and discourse processing are considered.

PMID- 17225509
TI  - Familiarity and relational preference in the understanding of noun--noun
      compounds.
AB  - When people are presented with noun-noun compounds, they tend to produce two main
      types of interpretation: relational and property interpretations. One theory of
      compounding maintains that relational interpretations are preferred over property
      ones. However, many of the studies supporting this relational preference
      hypothesis appear to be vitiated by a failure to control for the familiarity of
      compounds. A rating study on so-called "novel" compounds used in previous studies
      is reported, which shows that many can be considered to be familiar. Then two
      experiments in which familiarity is controlled are presented, to test the
      relational preference hypothesis, using a sensibility judgment task (Experiment
      1) and a comprehension judgment task (Experiment 2). The results show that
      familiarity has a clear effect on the ease of understanding of noun-noun
      compounds but that there is no hard evidence for relational preference. The
      implications of these results for the empirical literature and for current
      theories are discussed.

PMID- 17225510
TI  - Repetition proportion biases masked priming of lexical decisions.
AB  - Although subjects have little or no awareness of masked primes, Bodner and Masson
      (2001) found that priming of lexical decisions is often enhanced when masked
      repetition primes occur on a high proportion of trials. We used baseline prime
      conditions to specify the locus of this repetition proportion (RP) effect. In
      Experiments 1A and 1B, a .8-RP group showed more priming than did a .2-RP group,
      and this RP effect was due to both (1) increased facilitation from repetition
      primes and (2) increased interference from unrelated primes. In Experiment 2, we
      used the baseline condition to show that subjects are sensitive to RP rather than
      to the proportion of unrelated primes. Direct comparisons of a given prime
      condition (repetition, unrelated) across RP conditions were more stable than were
      comparisons relative to the baseline condition. The increased costs and benefits
      of repetition priming when RP is higher implicate a context-sensitive mechanism
      that constrains accounts of masked priming.

PMID- 17225511
TI  - Dissociating the influence of familiarity and meaningfulness from word frequency
      in naming and lexical decision performance.
AB  - Performance in two experiments was compared on a list of words of high and low
      frequency in which familiarity/meaningfulness (FM) was balanced and on a list of
      high- and low-frequency words in which FM was confounded with frequency (i.e.,
      high frequency--high familiarity vs. low frequency--low familiarity). Both
      repetition and task (lexical decision and naming) were investigated. In the
      lexical decision task of Experiment 1, both frequency and repetition effects were
      larger in the list with FM confounded than in the list with FM matched. In the
      naming task, frequency and repetition effects and their interaction were
      significant, but there was no influence of FM list context. In Experiment 2, in
      which the repetitions occurred across blocks, as opposed to randomly intermixed
      within a list, similar results were found; however, there was no interaction
      between list and repetition. The results suggest that an evaluation of items in
      terms of their meaning and familiarity explains a large part of the variance,
      only in lexical decision. These dimensions may be cued both by subjective
      feelings of familiarity and the extent to which semantic information is available
      and by episodic traces due to recent encounters with the item.

PMID- 17225512
TI  - Relational processing and working memory capacity in comprehension of relative
      clause sentences.
AB  - Previous research has indicated that the cognitive load imposed by tasks in
      various content domains increases with the complexity of the relational
      information processed. Sentence comprehension entails processing noun-verb
      relations to determine who did what to whom. The difficulty of object-extracted
      relative clause sentences might stem from the complex noun-verb relations they
      entail. Across three studies, participants read 16 types of object- and subject
      extracted relative clause sentences at their own pace and then responded to a
      comprehension question for each sentence. Relational processing was assessed
      using a premise integration task or a Latin square task. These tasks predicted
      comprehension of object-relatives before and after controlling for subject
      relatives. Working memory (WM) capacity was assessed using reading span or
      forward and backward digit span tests. WM tasks predicted comprehension of object
      relatives before but not after controlling for subject-relatives. Comprehension
      of object-relatives relied more heavily on a domain-general capacity to process
      complex relations than on WM capacity.

PMID- 17225513
TI  - Hemispheric processing of inferences: the effects of textual constraint and
      working memory capacity.
AB  - In this study, we investigated hemispheric differences in the generation of
      bridging and predictive inferences. Participants read texts that provided either
      strong or weak causal constraints for a particular bridging (Experiment 1) or
      predictive (Experiment 2) inference and performed a lexical decision task to
      inference-related targets presented to the left or the right hemisphere.
      Facilitation for strongly constrained bridging and predictive inferences was
      found in both hemispheres. In contrast, facilitation for weakly constrained
      inferences was stronger in the right than in the left hemisphere for both
      bridging and predictive inferences, although for the latter there was some
      facilitation in the left hemisphere as well. We also considered whether these
      effects differ as a function of the working memory capacity of the reader. High
      working memory capacity readers showed greater facilitation for strongly
      constrained inferences than for weakly constrained inferences in both
      hemispheres, whereas low working memory capacity readers showed this same pattern
      in the left hemisphere but showed equal facilitation for strongly and weakly
      constrained inferences in the right hemisphere. These results suggest that
      hemispheric processing, textual constraint, and working memory capacity interact
      to affect how readers generate causal inferences.

PMID- 17225514
TI  - Contextual knowledge reduces demands on working memory during reading.
AB  - An experiment is reported in which young, middle-aged, and older adults read and
      recalled ambiguous texts either with or without the topic title that supplied
      contextual knowledge. Within each of the age groups, the participants were
      divided into those with high or low working memory (WM) spans, with available WM
      capacity further manipulated by the presence or absence of an auditory target
      detection task concurrent with the reading task. Differences in reading
      efficiency (reading time per proposition recalled) between low WM span and high
      WM span groups were greater among readers who had access to contextual knowledge
      relative to those who did not, suggesting that contextual knowledge reduces
      demands on WM capacity. This position was further supported by the finding that
      increased age and attentional demands, two factors associated with reduced WM
      capacity, exaggerated the benefits of contextual knowledge on reading efficiency.
      The relative strengths of additional potential predictors of reading efficiency
      (e.g., interest, effort, and memory beliefs), along with knowledge, WM span, and
      age, are reported. Findings showed that contextual knowledge was the strongest
      predictor of reading efficiency even after controlling for the effects of all of
      the other predictors.

PMID- 17225515
TI  - Distinctiveness revisited: unpredictable temporal isolation does not benefit
      short-term serial recall of heard or seen events.
AB  - The notion of a link between time and memory is intuitively appealing and forms
      the core assumption of temporal distinctiveness models. Distinctiveness models
      predict that items that are temporally isolated from their neighbors at
      presentation should be recalled better than items that are temporally crowded. By
      contrast, event-based theories consider time to be incidental to the processes
      that govern memory, and such theories would not imply a temporal isolation
      advantage unless participants engaged in a consolidation process (e.g., rehearsal
      or selective encoding) that exploited the temporal structure of the list. In this
      report, we examine two studies that assessed the effect of temporal
      distinctiveness on memory, using auditory (Experiment 1) and auditory and visual
      (Experiment 2) presentation with unpredictably varying interitem intervals. The
      results show that with unpredictable intervals temporal isolation does not
      benefit memory, regardless of presentation modality.

PMID- 17225516
TI  - [A primary study about the correlation between superantigens produced by
      Staphylococcus aureus and chronic rhinosinusitis with nasal polyps].
AB  - OBJECTIVE: To study the role of superantigens produced by Staphylococcus aureus
      in the pathogenesis of nasal polyps. METHOD: sinonasal mucus and polyp/mucosa
      tissue were obtained from sixty-nine patients with chronic rhinosinusitis (42
      patients with bilateral nasal polyps, 27 without nasal polyps). Samples from
      twelve normal subjects were also obtained for comparative negative controls.
      Mucus specimens were cultured for bacteria. Tissue specimens were assayed by
      ELISA for staphylococcal exotoxins. In addition, the histopathology of nasal
      polyps was studied. The paraffin sections were stained with hematoxylin and
      eosin, and these were examined for eosinophil counts. RESULT: The percentages of
      Staphylococcus aureus in sinonasal mucus were 7.1 for chronic rhinosinusitis with
      nasal polyp (CRSwNP) subjects, 3.7% for chronic rhinosinusitis without nasal
      polyps (CRSsNP). and 0 for controls respectively. There were no significant
      differences between these groups. In CRSwNP subjects 23 of 42 samples (54.76%)
      demonstrated reactivity for at least one staphylococcal exotoxin. There were no
      positive results in the CRSsNP or control groups. The mean eosinophil counts were
      23. 94+/-13. 88 in CRSwNP group, 0.29+/-0.51 in CRSsNP group, and 0. 08+/-0.28 in
      controls. The differences in these three groups were all significant ( P <0.05).
      There was a trend toward higher eosinophil levels in polyps of ELISA-positive
      patients compared with that of ELISA-negative patients, although this was not
      statistically different ( P >0.05). CONCLUSION: There were correlation between
      Staphylococcal superantigens and nasal CRSwNP, and superantigens were possible
      etiological agents in the pathogenesis of CRSwNP.

PMID- 17225517
TI  - [The effects of endoscopic sinus surgery on nasality and nasal patency].
AB  - OBJECTIVE: The purpose of this study was to describe the changes of resonance
      characteristics of the nasal cavity (including nasal sinuses) and nasal airway
      resistance (NAR) after endoscopic sinus surgery (ESS), through objective
      measurement of nasality and NAR before and after ESS. METHOD: Sixty- eight
      patients received the examinations of nasality and NAR using Nanometer and Atmos
      Rhinomanometry before and after ESS separately. RESULT: The nasality of patients
      with type III and type II stage 2, stage 3 chronic sinusitis was obviously
      improved ( P <0. 05), but still below the normal range 1 month after ESS. The
      nasality didn't recover to the normal level 3 months postoperatively. However the
      total NAR apparently decreased 1 months after ESS ( P <0. 01) and returned to
      normal 3 months postoperatively. Nasality and the total NAR of patients in type
      II stage 1 turned to normal 1 month after ESS. There are no distinctive changes
      in nasality and total NAR of type I stage 1 patients. CONCLUSION: The total NAR
      significantly decreased close to normal among the patients with severe sinus
      or/and nasal lesions after ESS, however nasality continued aberrant for a
      relatively long period. It is suggested that nasality can't be ameliorated
      immediately after ESS. On the contrary, it is possible to bring some undesirable
      effects to the professional voice users, such as announces, for the changed
      resonance characteristics of the nasal cavity due to the excessive destruction of
      its normal structure.

PMID- 17225518
TI  - [Effects of remifentanil in children undergoing endoscopic-assisted
      adenoidectomy].
AB  - OBJECTIVE: To observe the effect of remifentanil on hemodynamic and
      angiotentratin- II in children undergoing endoscopic-assisted adenoidectomy.
      METHOD: Thirty patients, ASA I -II , were randomly divided into two groups ,
      remifentanil group and fentanyl group. Remifentanil group received remifentanil
      combined with propofol anesthesia, fentanyl group received fentanyl combined with
      propofol anesthesia . Vecuronium was given as muscle relaxant in both groups.
      ECG, HR, BP, Sa02 were monitored in both groups during operation,and peripheral
      venous blood samples were taken on 1d before operation(T1),at the time of
      endotracheal intubation (T2 ), 10 minutes after operation beginning (T3 ),5
      minutes after extubation (T4 ) for check angiotentratin- II , then recorded the
      time of anesthesia, the time of recovery from anesthesia and the time of
      extubation. RESULT: Comparing with T1, T2, and T3 were significant lower in both
      group about the HR, BP and angiotentratin-II. There was no significant difference
      in two groups about SaO2. HR and BP is little lower in remifentanil group than in
      fentanyl group . The anesthesia time was significantly longer in Remifentanil
      group than that in fentanyl group. The recovery time was significantly shorter in
      Remifentanil group than that in fentanyl group. The extubation time was
      significantly shorter in remifentanil group than that in fentanyl group.
      CONCLUSION: Remifentanil is better than fentanyl for stabilizing
      hemodynamic,decreasing the stress responses,reducing the time of recovery and
      extubation in children undergoing endoscopic-assisted adenoidectomy.

PMID- 17225519
TI  - [Study on correlation between HPV57 infection and the etiology of IP].
AB  - OBJECTIVE: To study correlation between HPV infection and the etiology of human
      papilloma and uncover the effects of HPV57 infection on IP, in order to provide a
      new way for IP precaution and treatment. METHOD: Sixty formalin-fixed, paraffin
      embedded specimens of IP were definitely diagnosed by pathologists. They were
      examined by the polymerase chain reaction (PCR) technique to amplify HPV DNA with
      HPV L1 consensus primer and HPV57 type-specific primer. Ten specimens of chronic
      sinusitis were taken as control group. RESULT: All of the sixty IP specimens
      showed negative after amplification by HPV 1.1 consensus primer MY09/11. There
      were forty-seven specimens(47/60, 78.3%) showed positive for HPV type 57 after
      amplification by HPV57 type-specific primer. CONCLUSION: Our findings suggest a
      possible role for HPV type 57 in the pathogenesis of nasal inverted papilloma.

PMID- 17225521
TI  - [The epidemic survey of children rhinosinal inflammatory diseases and their
      correlation with asthma in Nanjing].
AB  - OBJECTIVE: To realize the epidemic features of rhinosinal inflammatory diseases
      in children and their correlation with asthma in Nanjing,China. METHOD: A
      questionnaire survey on children chronic rhinosinusitis (CRS) and airway diseases
      was conducted among 1087 elementary school children, aged from 9 to 10, of seven
      schools in Nanjing city by random cluster sampling, from March to September,
      2004. The questionnaires include such questions as age, gender, family history,
      basis diseases, inducements, environment, therapy, correlative lower airway
      diseases and so on. The survey included screening suspects of CRS and allergic
      rhinitis (AR) by filling up the questionnaires by their parents and then special
      examination withtion of asthma of children was obtained by inquiring whether
      children were diagnosed by physician in last 12 months. The results were dealt
      with statistics. RESULT: Nine hundred and eighty nine questionnaires were
      returned. The response rate was 91% and 942 questionnaires were available. The
      prevalence rate of CRS of children aged from 9 to 10 was 8.8% in Nanjing city.
      The prevalence rate of AR was 5.1%. The prevalence rate of asthma of children was
      5.3%. The incidences of asthma of children with CRS and AR were 19.3% and 39.6%
      respectively, while that of children without rhinosinal inflammatory diseases was
      1. 8%. The results showed that the differences of the incidences of asthma
      between children with CRS, AR and without rhinosinal inflammatory diseases were
      statistically significant( P <0.01). CONCLUSION: Chronic rhinosinusitis is a
      common disease in children. The prevalence rates of CRS and AR in children aged
      from 9 to 10 in Nanjing city were 8.8% and 5. 1%. The incidence of asthma in
      children with rhinosinal inflammatory diseases is markedly higher than that in
      children without these diseases.

PMID- 17225520
TI  - [The clinical study about the serum total and specific IgE levels in Artemisia
      pollen-induced allergic rhinitis patients].
AB  - OBJECTIVE: The aim of our study was to clarify the diagnosis value of total IgE
      and the relationship between total and specific IgE. METHOD: Eight-seven
      Artemisia pollen-sensitive allergic rhinitis patients with obvious autumn onset
      and 80 nonatopic healthy controls were recruited for this study. Serum levels of
      total IgE were determined by using the Elecsys IgE reagent kit (Roche). Serum
      specific IgE antibodies against Artemisia pollen were measured by using a
      fluorescent enzyme immunoassay (UniCAP system, Pharmacia and Upjohn Diagnostics).
      RESULT: The serum total IgE levels in patients with allergic rhinitis were
      compared with the controls. The total IgE levels of the patients were much higher
      than those of the controls(Geometric mean of the patients and the controls were
      0. 185 U/L and 0. 050 U/L respectively, P <0.01). The correlation of the serum
      Artemisia pollen specific IgE and total IgE levels in patients with allergic
      rhinitis was made. No correlation was found between the total and specific IgE
      levels ( P >0. 05). CONCLUSION: There are some reference values for the serum
      total IgE levels to the diagnosis of the Artemisia pollen-induced allergic
      rhinitis patients. There are no correlation between the serum Artemisia pollen
      specific IgE and total IgE levels in patients with allergic rhinitis. Its value
      is limited to predict the specific value according the total IgE.

PMID- 17225522
TI  - [Expression and its significance of STAT3, STAT5, Survivin and Ki67 in nasal NK/T
      cell lymphoma].
AB  - OBJECTIVE: To study the expression and its significance of STAT3, STAT5, Survivin
      and Ki67 in the Epstein-Barr virus associated nasal NK/T cell lymphoma. METHOD:
      The expression of STAT3, STAT5, Survivin and Ki67 were detected with
      immunohistochemistry in 25 cases of nasal NK/T cell lymphoma, and their
      relationship was analyzed. Nasal cavity tissues from 20 cases of chronic
      sinusitis were as the control group. RESULT: The positive rates of STAT3 in the
      lymphoma and in control group were 56% and 10%, respectively (P <0.01). The
      positive rates of STAT5 in the lymphoma and in control group were 68% and 15%,
      respectively (P <0.01). The positive rates of Survivin and Ki67 of nasal NK/T
      cell-lymphoma were 68% and 72%, respectively; but it in the control group was 0%
      and 20%, respectively, P <0.01. The expression of STAT3 was positively related to
      that of Survivin and Ki67(r =0. 428, P <0. 05 and r =0. 704, P <0. 01); The
      expression of STAT5 was not related to that of Survivin and Ki67. CONCLUSION: The
      pathway of STAT may play a role in the development of nasal NK/T cell lymphoma.
      STAT maybe take part in the formation of nasal NK/T cell lymphoma through
      induction of Survivin and Ki67.

PMID- 17225523
TI  - [Study of pharyngeal anatomical diameter in patients with obstructive sleep apnea
      hypopnea syndrome before and after uvulopalatopharyngoplasty].
AB  - OBJECTIVE: To explore the changes of oropharynx in patients with obstructive
      sleep apnea-hypopnea syndrome(OSAHS) before and after long-term
      uvulopalatopharyngoplasty with uvula reserved completely. METHOD: Thirty-one
      patients with OSAHS were studied. The following indexes were measured before and
      after uvulopalatopharyngoplasty: length of uvula, width of uvula base, distance
      between two-side pillars (DBTP), distance between uvula and posterior pharyngeal
      wall(DBUP), length of soft palate, perimeter of neck and body mass index (BMI).
      RESULT: The postoperative length of uvula, width of uvula base, DBTP, DBUP
      changed significantly after uvulopalatopharyngoplasty( P <0.05). The
      postoperative length of soft palate was significantly less than that before
      uvulopalatopharyngoplasty( P <0.05). There was no significance difference in BMI
      and perimeter of neck between preoperative and postoperative patients( P >0.05).
      CONCLUSION: The uvulopalatopharyngoplasty with uvula reserved completely is an
      effective method to solve the airway constriction, especially the oropharynx
      constriction. Transverse diameter could be enlarged to the length of normal
      adults.

PMID- 17225524
TI  - [Management in squamous cell carcinoma of maxillary sinus with orbital invasion].
AB  - OBJECTIVE: To explore the orbital management in advanced squamous cell carcinoma
      of maxillary sinus with orbital invasion. METHOD: Forty-six postoperative cases
      of advanced squamous cell carcinoma of maxillary sinus with orbital invasion were
      followed up. Two,three,five-year survival rates and 2-year recurrence rates were
      analysed in,orbital bone invaded group, periorbit invaded group and orbital
      content invaded group. RESULT: Two, three,five-year survival rates and 2-year
      recurrence rates were 65.2%, 55.6%, 46.7% and 38.1% in orbital bone invaded
      group; 57.1%, 50.0%, 45.5% and 53.8% in periorbit invaded group; 44. 4%, 37. 5%,
      37. 5% and 62. 5% in orbital content invaded group, respectively. Survival rates
      of three groups descended and recurrence rates of three groups ascended but
      without statistical significance( P >0. 05). CONCLUSION: During the surgery for
      advanced squamous cell carcinoma of maxillary sinus with orbital invasion without
      the evidence of optical nerve and eye ball involvement, preservation of orbital
      contents is considerable even though the orbital bone and periorbit are involved
      by the tumor.

PMID- 17225525
TI  - [Clinical value of radionuclide imaging in differentiate the origin of cervical
      mass].
AB  - OBJECTIVE: To study the clinical value of thyroid imaging in differentiate the
      origin cervical mass. METHOD: Sixty-nine patients with cervical mass were
      subjected to 99mTc-pertechnetate imaging. 99Tc-MIBI hot spot imaging and
      perfusion imaging were performed in some of patients with cold or cool nodules.
      The findings of thyroid imaging were compared with follow up and histopathologic
      results. RESULT: Thirty-three of 69 patients were found with thyroid nodules, 36
      patients mass were outside thyroid. Twelve of 33 thyroid nodules were found to be
      subacute thyroiditis. Two cases regarded as thyroglossal duct cyst were found to
      be ectopic thyroid glands. Twenty-seven of 36 masses out side thyroid were
      thyroglossal duct cysts. CONCLUSION: 99m Tc-pertechnetate imaging, 99mTc-MIBI hot
      spot imaging and perfusion imaging are useful to differentiate the origin of
      cervical mass, and differentiate ectopic thyroid from thyroglossal duct cyst.

PMID- 17225526
TI  - [Effect of ephedrine on nasal cavity mucosa and study on therapy of ATP to the
      effect].
AB  - OBJECTIVE: To observe the effects of ephedrine on histomorphology and
      ultrastructure of nasal cavity mucosa from the healthy SD rats and explore the
      intervenient role of adenosine triphosphate(ATP). METHOD: Twenty-three SD rats
      were divided randomly into three groups: Group A as control group; Group B for
      ephedrine; Group C for ephedrine and ATP (injection of ATP into peritoneal while
      ephedrine was given). Nasal cavity mucosa were taken for light microscopy (LM),
      transmission electron microscopy (TEM) at the 1st, 2nd, 3rd and 8th week of the
      experiment. RESULT: The damages in Group B of nasal cavity mucosa of the 1st,
      2nd, 3rd week was aggravated gradually, histomorphology and ultrastructure of
      nasal cavity mucosa had no recovered after withdrawing drug until 8th week. Few
      damages in Group C of nasal cavity mucosa had been found in 1st week and a few
      damages were found in 2nd and 3rd week. The injured cells recovered definitely
      after stopping ephedrine and continuous application of ATP for another 5 weeks.
      CONCLUSION: The nasal cavity mucosa of SD rats can be damaged by ephedrine and
      the degree of damages of which becomes more serious with the increase of time.
      Furthermore the damages do not recover. ATP can alleviate the damages of nasal
      cavity mucosa from SD rats caused by ephedrine and prevent nasal cavity mucosa
      from the damages induced by ephedrine.

PMID- 17225527
TI  - [Advances in research of chemical constituents and pharmacological activites of
      Ephedra].
AB  - The collected information is an attempt to cover the more recent developments in
      the phytochemistry and pharmacology of this genus. During the past years,
      alkaloids, flavonoids, volatile oils, organic acids, polysaccharides, tannins and
      phenolic constituents have been isolated from Ephedra. Pharmacological studies
      are described according to hypoglycemic effects, anticoagulated blood properties,
      depressurization, immunosuppressive activity, antioxidation and antivirus
      activity and so on. The information summarized here is intended to provid a
      rational foundation for the futher development and utilization of Ephedra which
      is rich in China.

PMID- 17225528
TI  - [A review of research on sustainable use of medicinal plants cropland in China].
AB  - In China, about 40% of traditional Chinese medicine (TCM) comes from cultivation
      in agrarian systems. The cropland is fundamental to the productions of medicinal
      plants, and the sustainable soil management is essential for sustainable using of
      the TCM resources, furthermore it affects the local economies of the medicinal
      plant production regions and the sustainable development of TCM agriculture. In
      this paper, the concept of the sustainable use of TCM cropland was discussed and
      the problems on sustainable soil management in China were analyzed from the
      aspects of resources and quality. The research advances in sustainable use of the
      medicinal plants cropland were reviewed from the aspects of continuous cropping
      obstacles, faming systems and degraded soil remediation. The strengthening
      research fields in the further were suggested.

PMID- 17225529
TI  - [Studies on market of drug delivery system product and drug delivery system of
      compound Chinese medicine].
AB  - Based on the progress in the world market of drug delivery system (DDS) product
      and the research profile of DDS of compound Chinese Medicine, The article puts
      forward a new method of studies on DDS of compound Chinese Medicine. It is
      expected that the theory of compatibility of compound Chinese Medicine can be
      shown and its role can be exerted to the largest extent with the application of
      pharmaceutics technology to change the mode of drug delivery of activated
      components of compound Chinese Medicine.

PMID- 17225530
TI  - [Screening strains for Trichoderma spp. for strong antagonism against ginseng
      root pathogens and study on their biological characters].
AB  - OBJECTIVE: To screen the Trichodenna spp. for strong antagonist against ginseng
      root pathogens. METHOD: The biological characters of ten Trichoderma strains were
      compared by culturing on different media. And their antagonistic activity against
      Phytophthora cactorum, Cylindrocarpon destructans and Rhizoctonia solani were
      measured on PDA. RESULT AND CONCLUSION: Tv04-2 and Th3080 showed a good growth on
      soil solution medium and PDA, and also showed high inhibitory efficacy to the
      three pathogens. The two Trichoderma strains showed different growth rate under
      light conditions and pH. Trichoderma strains were sensitive to most fungicides
      used in ginseng root disease controlling, however Tv04-2 was not sensitive to the
      fungicide Junchong Jueba.

PMID- 17225531
TI  - [Effect of HKL-4 on active oxygen metabolism and photochemical efficiency in
      licorice leaf].
AB  - OBJECTIVE: To study the effects of HKL-4 on physiological changes during growth
      of leaves. METHOD: Using licorice (Glycyrrhiza uralensis) as material, the
      effects of HKL-4 on active oxygen metabolism and photochemical efficiency in
      licorice leaf were determined under field condition. RESULT AND CONCLUSION: The
      contents of chlorophyll, activity of SOD and CAT increased, while the MDA
      contents in leaves decreased. The senescence was delayed, so that the
      photochemical efficiency (Fv/Fm) was increasing comparing to the control.

PMID- 17225532
TI  - [Studies on HPLC fingerprint of cortex moutan].
AB  - OBJECTIVE: To establish a HPLC fingerprint for quality evaluation of Cortex
      Moutan. METHOD: The HPLC chromatographic fingerprinting of 30 lots of Cortex
      Moutan was established and major peaks were identified by LC-MS and MS-MS.
      RESULT: The HPLC fingerprint of Cortex Moutan was established, showing 15
      characteristic peaks. The areas of these peaks were found to complied with the
      following rule: paeonol > 1, 2, 3, 4, 6-penta-O-galloyl-glucos > methyl gallate >
      galloylpaeoniflorin > gallic acid > oxypaeoniflorin > other compounds.
      CONCLUSION: The chromatographic fingerprinting of Cortex Moutan with high
      specificity can be used to control its quality and monitor lot to lot
      consistency.

PMID- 17225533
TI  - [Studies on dynamic variation of six isoflavones contents in rhizomes of
      Belamcanda chinensis].
AB  - OBJECTIVE: To study the monthly dynamic variation of the contents of six
      isoflavones in the rhizomes of Belamcanda chinensis cultivated in Nanjing, and
      decide optimum harvesting times. METHOD: HPLC method was used to determine the
      contents of six isoflavones in the samples collected at different times. RESULT:
      It was shown that the total contents of six isoflavones in the rhizomes of B.
      chinensis collected in April were the highest. CONCLUSION: The most optimum
      collecting time of rhizomes of B. chinensis cultivated in Nanjing should be in
      April.

PMID- 17225534
TI  - [Determination of plumbagin in different parts of Plumbago zeylanica by RP-HPLC].
AB  - OBJECTIVE: To develop a RP-HPLC method to determine plumbagin in Plumbago
      zeylanica, and to investigate contents of plumbagin in different parts of. P.
      zeylanica. METHOD: The analysis was carried out at 30 degrees C on a Kromasil
      C18, column eluted with a mobile phase consisting of a mixture of methanol-water
      (65: 35). The flow rate was 1 mL x min(-1), the detector wavelength was 213 nm.
      RESULT: The calibration curve was linear within the concentration ranges of 0.020
      8-0. 104 microg (r = 0. 9999). The average recovery was 98.7%. The contents in
      the root, stem and leaf were 0.394 5%, 0.050 8%, 0.031 4% respectively.
      CONCLUSION: This method is simple, accurate, replicate and suitable for the
      determination of plumbagin in P. zeylanica.

PMID- 17225536
TI  - [Chemical constituents in root of Zanthoxylum nitidum].
AB  - OBJECTIVE: To study the chemical constituents of Zanthoxylum nitidum. METHOD:
      Column chromatography on Silica gel and Sephadex LH - 20, and recrystallization
      were applied for the isolation and purification of the constituents. The
      structures were elucidated on the basis of spectral analysis, chemical evidences
      and by comparison with the data reported in literature. RESULT: From the CHCl3
      fraction and n-butanol fraction of the EtOH extract of the roots of Z. nitidum,
      10 compounds were isolated and identified as 2, 4-dihydroxypyrimidine (1),
      syringic acid (2) , 2, 6-dimethoxy-1, 4-benzoquinone (3) , 4-hydroxybenzoic acid
      (4), ethylparaben (5), (Z)-3-(2, 3, 4-trimethoxyphenyl) acrylic acid (6), 5, 6, 7
      trimethoxycoumarin (7), stigmast-9 (11) -en-3-ol (8), daucosterol (9), beta
      sitosterol (10). CONCLUSION: Compounds 1-9 were isolated and identified from the
      roots of Z. nitidum for the first time. Furthermore, we note here the first
      isolation of compound 6 as a natural product.

PMID- 17225535
TI  - [Determination of 3 kinds of components in huanglian jiedu decoction by HPLC
      under different UV wavelengths].
AB  - OBJECTIVE: To determinate 3 kinds of effective components (5 compounds) in
      Huanglian Jiedu decoction at the same time, namely berberine, palmtine,
      jatrorrhizine, baicalin and geniposide. METHOD: A HPLC method detected by 3
      different UV wavelengths 345 nm for berberine, palmtine and jatrorrhizine, 280 nm
      for baicalin, 238 nm for geniposide. Diamonsil C18 (4.6 mm x 250 mm, 5 microm)
      column was used, the mixture of H2O (A) , CH3OH (B) and 0.05% H3PO4 solution (C)
      as mobile phase in gradient mode. The column temperature was 35 degrees C and the
      flow rate was 1 mL x min(-1). RESULT: This method was applied to determined 5
      compounds in Huanglian Jiedu decoction rapidly and accurately. CONCLUSION: The
      quality control method is convenient, reasonable and credible for Huanglian Jiedu
      decoction.

PMID- 17225537
TI  - [Studies on chemical constituents in roots of Rumex dentatus].
AB  - OBJECTIVE: To investigate the active constituents from Rumex dentatus. METHOD:
      Compounds were isolated by silica gel, Sephadex LH -20 and ODS column
      chromatography and identified by chemical and spectroscopic methods. RESULT: Ten
      compounds were obtained and identified as helonioside A (1), gallic acid (2),
      isovanillic acid (3), p-hydroxycinnamic acid (4), succinic acid (5), n-butyl-beta
      D-fructopyranoside (6), quercetin (7), hexadecanoic acid 2, 3-dihydroxy propyl
      ester (8), beta-sitosterol (9) and daucosterol (10). CONCLUSION: Compounds 1, 3-6
      and 8 were isolated from the genus of Rumex for the first time.

PMID- 17225538
TI  - [Studies on chemical constituents of Euphorbia sororia].
AB  - OBJECTIVE: To study the chemical constituents of the aerial parts of Euphorbia
      sororia. METHOD: Isolation and purification were carried out by silica gel and
      Sephadex LH -20 column chromatographies. Compounds were identified by
      physicochemical properties and spectral analysis. RESULT: Ten compounds were
      isolated from the plant . Their structures were identified as kaempferol (1),
      scopoletin (2) , kaempferol 3-O-glucopyranoside (3) , quercetin (4) , vanillic
      acid (5) , E-p-hydroxycinnamic acid (6) , protocatechuic acid (7), 6, 7
      dihydroxycoumarin (8), beta-sitosterol (9), and daucosterol (10) , respectively.
      CONCLUSION: All the above compounds were isolated from the plant for the first
      time.

PMID- 17225539
TI  - [Studies on chemical constituents from root of Clematis hexapetala].
AB  - OBJECTIVE: To study the chemical constituents from the roots and rhizomes of
      Clematis hexapetala. METHOD: The compounds were separated by means of solvent
      extraction, repeated chromatography with silica gel and HPLC. The structures were
      determined by spectral analysis. RESULT: Nine compounds were isolated as
      friedelin (1) , anemonin (2) , beta-sitosterol (3) , palmitic acid (4) , vanillic
      acid (5) , isolariciresinol (6) , 5-hydroxumethyl-5H-furan-2-one (7) , n-nonane
      (8) , daucosterol (9). CONCLUSION: All the compounds were isolated from the plant
      for the first time.

PMID- 17225540
TI  - [Simultaneous determination of three active constituents in cortex moutan by RP
      HPLC].
AB  - OBJECTIVE: To establish a RP-HPLC method for the simultaneous determination of
      gallic acid, paeoniflorin and paeonol in Cortex Moutan. METHOD: The analysis was
      carried out on a column of YMC-C18 (4. 6 mm x 250 mm, 5 microm), and gradient
      elution was used for the baseline separation of these three constituents with the
      different detection wavelength. RESULT: The linear ranges for gallic acid,
      paeoniflorin and paeonol were 0.0130-0.267, 0.0880-1.76 and 0.164-3.28 microg,
      respectively. Their average recoveries were 104.3%, 101.7% and 99.5%,
      respectively. CONCLUSION: The method was successfully applied to the
      determination of gallic acid, paeoniflorin and paeonol in Cortex Moutan from the
      different drugstores. It was shown in this study that the proposed method could
      be used to evaluate the quality of the medicinal plants or herbal preparations
      containing gallic acid, paeoniflorin and paeonol.

PMID- 17225541
TI  - [Study on therapeutic effects of series of muskone on myocardial infarction
      canines].
AB  - OBJECTIVE: To observe the effects of the series of Muskone (the Muskone includes
      Slender Dutchmanspipe Root, Tumuxiang, and not Slender Dutchmanspipe Root) on
      myocardial ischemia, myocardial infarction and hematological index in
      experimental canines, and to explain the pharmacological action and
      characteristic of its therapeutic effect on ischemic heart disease. METHOD: The
      range and degree of myocardial ischemia was evaluated by epicardial electrogram
      mapping, and the range extent of myocardial infarction was determined by
      quantitate histology (N-BT staining method). Meanwhile, the changes of ET, TXB2,
      6-Keto-PGF1alpha were determined to study the effects of the series of Muskone on
      myocardial ischemia, myocardial infarction and hematological index in
      experimental canines. RESULT: The series of Muskone can improve myocardial
      ischemia and infarction in experimental canines, and relieve significantly the
      degree of myocardial ischemia (Sigma-ST) determined by epicardial electrogram
      mapping, decrease the range of myocardial ischemia (N-ST) determined by
      epicardial electrogram mapping and decrease infarction zone determined by N-BT
      staining method. And it has a significant inhibition on activity of ET induced by
      myocardial ischemia and infarction, and increases 6-Keto-PGF1alpha and 6-Keto
      PGF1alpha/TXB2 induced by myocardial ischemia. CONCLUSION: The series of Muskone
      has significant therapeutic effect on myocardial infarction.

PMID- 17225542
TI  - [Study on irritation of calcium oxalate crystal in raw Pinellia ternata].
AB  - OBJECTIVE: Confirm the irritation of needle-like calcium oxalate crystals in raw
      Pinellia ternata. METHOD: Comparing the irritations of raw P. ternate containing
      calcium oxalate crystals, the raw P. ternate no containing calcium oxalate
      crystals, the pure needle-like calcium oxalate crystals isolated from raw P.
      ternata, the extracts of water and various solvents from raw P. ternate. by using
      the model of rabbits' eyes. Studying the quantity effect relationship of
      different concentration suspensions of needle-like calcium oxalate crystal
      isolated from raw P. ternate on rabbits' eyes. Observing the shape and appearance
      of calcium oxalate crystals in raw P. ternate and raw India Madder Root by the
      electro microscope and comparing their irritation degrees with the same contents
      of calcium oxalate crystals. RESULT: Calcium oxalate crystals in raw P. ternata
      showed very strong irritation property. Under the same content of calcium oxalate
      crystals, the irritation of raw P. ternata and pure needle-like calcium oxalate
      crystals isolated from raw P. ternate had no significant difference. The
      concentrations of needle-like calcium oxalate crystals were do relative to the
      degree of irritation on rabbits' eyes and they showed undoubted quantity-effect
      relationship. CONCLUSION: Calcium oxalate crystal is the irritation component in
      raw P. ternata.

PMID- 17225543
TI  - [Study on bile excretion of scutellarein].
AB  - OBJECTIVE: A HPLC-ECD method was established to determine scutellarin in rat
      bile. METHOD: The analytical column was Prontosil C18 (4.6 mm x 250 mm, 5
      microm), and the mobile phase was consisted of methanol, 50 mmol x L(-1)
      phosphate buffer (adjusted by phosphoric acid to pH 2. 6), and tetrahydrofuran
      (40: 60: 10) , the flow rate was 1.0 mL x min(-1); the potential electrode
      voltage was 100 mv. RESULT: Concentration profile of scutellarin in rat bile was
      shown in this paper after oral administration of scutellarein. CONCLUSION: Only
      scutellarin was detected in rat bile, while both of scutellarin and scutellarein
      were detected in rat plasma.

PMID- 17225544
TI  - [Study on anti-tumor effect of medicinal fungi Phellinus igniarius extracts].
AB  - OBJECTIVE: To study the inhibiting effect of medicinal fungi Phellinus igniarius
      extracts on S180 tumor and the immunoregulation effect on the S180-induced tumor
      mice. METHOD: S180 mice were orally given 100, 200, 400 mg x kg(-1) dosage of P.
      igniarius extracts, then the inhibition grow effect, spleen index, and thyme
      index were measured. RESULT: Medicinal fungi P. igniarius extracts can increase
      the spleen index and thyme index and the inhibiting tumor rate was 31.88%,
      46.25%, 53.13%, respectively. Also, medicinal fungi P. igniarius extracts can
      prolong life in mice. CONCLUSION: The medicinal fungi P. igniarius extracts show
      obviously anti-tumor effect and immunoregulation effect.

PMID- 17225546
TI  - [Effects of annao tablet on S100B and NPY of cortex in chronic epilepsy rats].
AB  - OBJECTIVE: To study the effects of Annao tablet (main component is beta-asarone)
      on S100B and NPY of cortex in chronic epilepsy rats. METHOD: The remedy was
      administered orally. The effects were observed in convulsion model induced by PG,
      then S100B protein and NPY of cortex were determined. RESULT: Annao tablet could
      depress the epileptic degree, postpone spasm latent period and reduce the wet dog
      sample (WDS) times. The remedy could decline S100B and NPY of cortex in chronic
      epilepsy rats. CONCLUSION: Annao tablet has obvious antiepileptic effects and can
      reduce the nerve cell damage induced by epilepsy.

PMID- 17225545
TI  - [Mechanism study of anti-influenza effects of Radix Isatidis water extract by red
      blood cells capillary electrophoresis].
AB  - OBJECTIVE: To research the mechanism of the inhibition effects of BWE on cell
      attachment of influenza virus by capillary electrophoresis. METHOD: The
      morphologic difference of red cells after treating with BWE infected by influenza
      virus was detected with microscope, capillary electrophoresis and HA. RESULT: The
      pretreatment of the normal cells with BWE inhibited the attachment of influenza
      to the cells, while no meaningful inhibition was observed when influenza virus
      was pretreated before being inoculated to cells. CONCLUSION: The results indicate
      that the inhibition effects of BWE on cell attachment of influenza virus may be
      an important mechanism of anti-influenza activity of Radix Isatidis Extracts.

PMID- 17225547
TI  - [A clinical study on a randomized, double-blind control of Chinese medicine
      granules in treatment of vascular dementia].
AB  - OBJECTIVE: To evaluate the effectiveness of Chinese medicine granules (Compound
      Chinese extract from herbs) in the treatment on senile vascular dementia. METHOD:
      One hundred and twenty patients meeting criteria for vascular dementia were
      selected from patients in Dongzhimen Hospital and were randomly assigned into a
      treatment group (n = 70 cases), given 1 package of Chinese medicine granules with
      1 placebo tablets, and a positive control group (n = 50 cases), given 1 tablets
      of Duxil with 1 package of placebo. All subjects took this medication 3 times a
      day for 2 months. Double-blind and double-moulding control were used in this
      study. At a baseline and end (two months later), all subjects were assessed using
      a battery consisting of MMSE and Blessed behavior measuring scale. RESULT: Both
      Chinese medicine granules and Duxil could remarkably increase the score of
      cognition and activity (P < 0.01). They had Similarly effectiveness and there was
      no statistical difference between the two groups in effectiveness of increasing
      memory scores. Chinese medicine granules was better than Duxil in increasing the
      scores of behavior (P < 0.05). CONCLUSION: Chinese medicine granules has certain
      effects on vascular dementia. And it has remarkable effectiveness in ameliorating
      the status of total body. And it can relieve the symptoms in vascular dementia.

PMID- 17225548
TI  - [Clinical study of treatment nonalcoholic fatty liver with qianggan capsule].
AB  - OBJECTIVE: To investigate the therapeutic effect of Qianggan capsule on the
      treatment of nonalcoholic fatty liver. METHODS: One hundred and twenty-two
      patients of nonalcoholic fatty liver were randomly divided into two groups, 64
      patients in the treated group were treated by Qianggan capsule, 5 granule every
      time, twice per day and the 58 patients in control group were treated by
      tiopronin, 0. 2 gram every time, third per day with a therapeutic course of 3
      months. RESULT: Serum levels of ALT and gamma-GT were decreased significantly
      after the treatment of Qianggan capsule (P <0.05). However, TG levels seemed
      decreased but have not significant difference after the treatment of Qianggan
      capsule. The serum level of ALT in control group decreased markedly after
      treatment (P < 0.05), but no obvious change was seen in gamma-GT and TG in
      control group after treatment. The total effective rate in the treated group was
      higher than those in the control group (79.69% vs 62.07%, P < 0.05). CONCLUSION:
      Qianggan capsule is an effective recipe in treating nonalcoholic fatty liver.

PMID- 17225549
TI  - Cloning around.

PMID- 17225551
TI  - A brave new world.

PMID- 17225550
TI  - Unraveling your DNA's secrets.

PMID- 17225552
TI  - Congratulations! It's a (you choose) boy/girl.

PMID- 17225553
TI  - Sexually active women may also benefit from HPV vaccine.

PMID- 17225554
TI  - Should family members be permitted to stay in the room during a code?

PMID- 17225555
TI  - Is your facility prepared for JCAHO imposters?

PMID- 17225556
TI  - Hands-on help. Surgical drains.

PMID- 17225557
TI  - Length of hospital stay determines 'usual time'.

PMID- 17225558
TI  - JCAHO's patient safety goals: a practical guide. Part 1.

PMID- 17225559
TI  - "But I'm not a psych nurse"!

PMID- 17225560
TI  - Gaining control over A-fib.

PMID- 17225561
TI  - Synthesis and bioactivity of aripiprazole derivatives.
AB  - Ten aripirazole (CAS 129722-12-9) derivatives were prepared and examined for
      dopamine receptor antagonist activity. The structures of these newly synthesized
      compounds were confirmed by their elemental analyses and by IR, 1H-NMR and mass
      spectra. It was demonstrated that all the new compounds have dopamine receptor
      antagonist activity to a certain extent. Three compounds showed more potent
      activity than aripiprazole.

PMID- 17225562
TI  - Synthesis and biological activities of some thiazolidin-4-ones.
AB  - In this study, fifteen 2,3-disubstituted-4-thiazolidinone derivatives were
      synthesized by the reaction of Schiff bases and alpha-mercaptoacetic acid. The
      structures of the compounds were elucidated by IR, 1H-NMR, 13C-NMR, mass spectral
      data and elementary analysis. The antihistaminic and anticholinergic activities
      of the compounds were determined by tests performed on isolated guinea pig
      trachea in comparison with aminophylline (CAS 317-34-0). Compound 15 (3-[3-(2
      methyl-piperidine-1-yl)propyl]-2-(4-methyl-phenyl)thiazolidin-4-one
      hydrochloride) showed the highest inhibition (53 %).

PMID- 17225563
TI  - Cardiovascular effects of the selective alphalA-adrenoceptor antagonist silodosin
      (KMD-3213), a drug for the treatment of voiding dysfunction.
AB  - The aim of this study was to assess the cardiovascular effects of silodosin (CAS
      160970-54-7, (-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy)
      phenoxy]ethyllamino)propyll-2,3-dihy-dro-1H-indole-7-carboxamide, KMD-3213), a
      potent selective alpha1A-adrenoceptor (AR) antagonist used for the treatment of
      dysuria. In conscious dogs, orally administered silodosin, at doses (0.2, 2 and
      20 mg/kg) considerably higher than the pharmacologically effective dose,
      decreased blood pressure. These doses, however, had no effects on heart rate or
      on the electrocardiogram (PR interval, QRS interval, QT interval or QTc). In
      addition, the cardiac effects of silodosin were evaluated in an in vitro
      electrophysiological study. Silodosin inhibited the human ether-a-go-go-related
      gene (HERG) tail current, leaving a residual tail current of 45 % control at 10
      micromol/L. However, the concentration that inhibited the HERG tail current was
      considerably higher than its affinity for alphal-ARs. These results suggest that
      while the alpha1B-AR subtype is mainly involved in the regulation of blood
      pressure, the alphalA-AR subtype is not. There seems to exist no evidence of a
      correlation between the function of alphal-AR and ECG changes reflecting
      inhibition of the HERG current. The cardiovascular profile of silodosin suggests
      therefore that it is a safe and well-tolerated drug.

PMID- 17225564
TI  - Effects of the novel non-steroidal anti-inflammatory compound [N-(2-thiolethyl)-2
      {2- [N'- (2,6- dichlorophenyl) amino] phenyl}acetamide on cytokines and
      apoptosis in ischaemic rat brain.
AB  - Ischaemia-reperfusion injury is associated with an inflammatory response as well
      as apoptosis in the affected area. Inflammatory responses are characterized,
      among others, by an increased production of several cytokines, while caspases are
      implicated in the control of apoptosis. The aim of the present work was to
      determine changes in the levels of inflammatory and apoptotic indices in the rat
      brain after cerebral ischaemia-reperfusion and to evaluate the effect of the non
      steroidal anti-inflammatory compound N-(2-thiolethyl)-2-{2-[N'-[2,6
      dichlorophenyl)aminolphenyl} acetamide on these indices. A cerebral ischaemia
      reperfusion rodent model was used to investigate, via immunohistochemical and
      colorimetric techniques, the presence in the brain and spleen of inflammatory
      enzymes cycloxygenases COX-1 and COX-2, cytokines interleukin (IL)-1beta, IL-4,
      IL-6, IL-10, IL-18, tumor necrosis factor alpha (TNF-alpha) and interferon gamma
      (IFN-gamma) as well as the activated form of caspase-3, in treated and untreated
      animals. Cerebral ischaemia-reperfusion caused elevated levels in the rat post
      ischaemia. Treatment with the antiinflammatory derivative reduced the elevation,
      caused by ischaemia, of IFN-gamma, TNF-alpha, IL-1beta IL-6, IL-18 and caspase-3
      levels at 3 days post ischaemia, while it increased the levels of IL-10. It was
      shown that the increase in concentrations of a wide range of cytokines involved
      in the inflammatory reaction causing brain damage after ischaemia-reperfusion can
      be partially reversed by the anti-inflammatory derivative used in this study.

PMID- 17225565
TI  - Synergistic effect of nitric oxide synthase and cyclooxygenase inhibitors on
      carrageenan-induced paw edema in rats.
AB  - The present study examined the effects of L-nitroarginine methylester (L-NAME,
      CAS 50903-99-6), a non-selective nitric oxide synthase (NOS) inhibitor,
      indometacin (IND, CAS 3305-29-1), a non-selective cyclooxygenase (COX) inhibitor,
      and a combination of these agents (L-NAME + IND) on carrageenan-induced paw edema
      for 4 h after the injection of carrageenan in rats. L-NAME at 10 and 30 mg/ kg
      but not 3 mg/kg (i.p.) decreased paw volume slightly but significantly only at 1
      h after the carrageenan injection. IND reduced paw volume slightly at 1 and 3
      mg/kg, and markedly at 10 mg/kg (p.o.). A combination of L-NAME and IND at a
      subthreshold dose (3 mg/kg, i.p. and 1 mg/kg, p.o., respectively) caused a marked
      reduction of paw edema, which was also confirmed by histopathological
      examinations. A combination of N-(3-(aminomethyl)benzyl)acetamidine (1400W, CAS
      180001-34-7), a selective inhibitor of inducible NOS, and IND at 3 mg/kg, i.p.,
      and 1 mg/kg, p.o., respectively, did not show synergistic anti-inflammatory
      effects. In conclusion, the combination of non-selective NOS and COX inhibitors
      had synergistic anti-inflammatory effects on carrageenan-induced paw edema at an
      early stage, suggesting negative crosstalk between the endogenous NOS-NO and COX
      PG pathways in the early stages of acute inflammation.

PMID- 17225566
TI  - Attenuation of ischemia/reperfusion injury in rats by the anti-inflammatory
      action of resveratrol.
AB  - Resveratrol (trans-3,4',5-trihydroxystilbene, CAS 501-36-0), a natural
      antioxidant and polyphenol found in grapes and wine, has been found to
      pharmacologically precondition the heart in nitric oxide (NO)-dependent manner.
      In the vascular system, NO functions as an endogenous inhibitor of leukocyte
      chemotaxis, adherence, and activation. The present study was designed to
      determine if resveratrol, through NO, can block the proadhesive molecules
      generated in the ischemic reperfused myocardium. Isolated hearts were prepared
      from properly anesthetized rats, and mounted on a Langendorff apparatus. The
      hearts were randomly assigned to one of the three groups: (i) control, (ii)
      resveratrol, and (iii) resveratrol + NG-nitro-L-arginine ethyl ester (L-NAME).
      The hearts were perfused in the absence (n = 6) or presence of 10 micromol/L
      resveratrol (n=6) or resveratrol + L-NAME (n = 6) for 15 min. All the hearts were
      then subjected to 30 min ischemia followed by 2 h of reperfusion. Ventricular
      function was monitored, infarct size and apoptotic cell death measured, and the
      proadhesive molecules and malonaldehyde formation determined in the perfusate.
      Resveratrol significantly improved postischemic ventricular function and reduced
      myocardial infarct size compared to the non-treated control group. The amount of
      proadhesive molecules including soluble intracellular adhesion molecule-1 (sICAM
      1), endothelial leukocyte adhesion molecule-1 (sE-Selectin) and vascular cell
      adhesion molecule-1 (sVCAM-1) were each significantly decreased during
      reperfusion in the resveratrol group. L-NAME, a NO blocker, completely abolished
      such beneficial effects of resveratrol. The results support an anti-inflammatory
      action of resveratrol through a NO-dependent mechanism.

PMID- 17225567
TI  - Disposition of 1,4,6,8-tetramethyl-furoquinolinone in normal and ascitic tumor
      bearing mice.
AB  - 1,4,6,8-Tetramethyl-2H-furo[2,3h]quinolin-2-one (FQ) belongs to a series of
      furocoumarin isosters, designed to obtain new drugs for photochemotherapy. The
      objective of this study was to characterize the disposition of orally
      administered 3H-FQ in normal and ascitic tumor bearing mice and to evaluate the
      influence of UVA irradiation in control mice. This compound was rapidly absorbed
      and its decay in serum was biphasic. Binding to serum proteins, which was maximum
      at 30 min (74 %), time-dependently declined. FQ was distributed to all the
      studied tissues, primarily to the liver and kidneys. The administered
      radioactivity was excreted mostly in the urine (43 %) and was associated with
      polar metabolites. The unchanged compound was not present to any detectable
      extent in the urine. Elimination in the faeces, that may include FQ not absorbed,
      was low (14 % of administered radioactivity), emphasizing the quantitatively
      efficient gastrointestinal absorption of the drug. UVA irradiation of FQ-treated
      mice for 2 h caused a significant increase in radioactivity measured in serum as
      well as in the liver. In mice bearing Ehrlich ascitic tumor, serum and tissue
      concentrations were lower than in control animals, possibly due to the larger
      volume of body fluids (10+/-4 ml of ascitic fluid) available for drug
      distribution.

PMID- 17225569
TI  - Kentucky's obesity epidemic.

PMID- 17225568
TI  - Compatibiliity and stability of furosemide and dexamethasone combined in infusion
      solutions.
AB  - AIM: The goal of palliative care is the achievement of the best quality of life
      for patients and their families. For this, the administration of drugs by
      subcutaneous infusion is frequently used since many patients have great
      difficulties in taking drugs orally and regular intramuscular injections are
      painful. Usually, drugs are combined in infusion solutions. The objective was
      therefore to study the compatibility and stability of dexamethasone sodium
      phosphate (CAS 2392-39-4) and sodium furosemide (CAS 54-31-9) combined in
      solutions destined to subcutaneous administration in palliative medicine.
      METHODS: Twelve different solutions were assessed during 15 days. Drug admixtures
      were prepared in polypropylene syringes using 0.9 % saline as diluent and stored
      at 4 degrees C and 25 degrees C in the dark. Initial concentrations were 3.33
      10.0 mg/ ml for sodium furosemide (dose range 40-120 mg/day) and 0.33-3.33 mg/ml
      (dose range 4-40 mg/day) for dexamethasone sodium phosphate. Quantification of
      both drugs was performed by high-performance liquid chromatography. RESULTS:
      After 5 days of storage at both temperatures, the maximum losses obtained were
      lower than 10 % for both drugs. However, after 15 days, slight
      precipitation/turbidity was observed in all mixtures. At this time, maximum
      losses of 20 % were obtained for both drugs. CONCLUSION: These results confirm
      the stability of mixtures prepared with sodium furosemide (< or = 120 mg/day) and
      dexamethasone sodium phosphate (< or = 40 mg/day) for a period of 5 days and with
      independence of their storage at 4 degrees C or 25 degrees C.

PMID- 17225570
TI  - Unstaged lung cancer in Kentucky.
AB  - Comparisons were made for unstaged lung cancer cases both to "staged" lung cancer
      cases and to unstaged cases from all other sites, in Kentucky for 1996-2000.
      Principal findings were that the likelihood of the lung cancer cases to be
      unstaged was greater when the cancer incidence report came from sources other
      than a hospital. This may implicate data system forces [for availability of
      necessary data for completing stage at diagnosis] rather than differences between
      cases per se. The risk of being unstaged by smoking status was reversed between
      lung cancer (lower risk) than for all other cancer sites (higher risk), an
      unexpected pattern. No difference for survival was found for unstaged versus
      staged lung cancer cases, as well as no differences for race and gender. The
      finding of no differences suggests that other forces (eg, age, source of payment)
      may contribute more greatly to one's likelihood of being unstaged with a
      diagnosis of lung cancer than for "all other cancer sites." These patterns pose
      provocative implications for how smoking status may influence clinical
      perspectives and those of persons faced with a diagnosis of cancer.

PMID- 17225571
TI  - The auction.

PMID- 17225578
TI  - [The patient in the center of the care network].

PMID- 17225579
TI  - ["The principal stake is to overcome institutional problems". Interview by
      Enrique Ledesma].

PMID- 17225580
TI  - [History of psychiatric networks].

PMID- 17225581
TI  - [The autistic child and his family in the center of the department level].

PMID- 17225582
TI  - [Physical care in psychiatry].

PMID- 17225583
TI  - [The job of social work, so that the "crazy person" remains a citizen].

PMID- 17225585
TI  - [The divided secret].

PMID- 17225584
TI  - [Collaborating relations in the care network].

PMID- 17225586
TI  - [Theatrical therapeutic expression workshop].

PMID- 17225587
TI  - [Evaluation of professional practices in managing suicidal patients].

PMID- 17225588
TI  - Titration instruments.

PMID- 17225589
TI  - Detection of bovine meat and bone meal in animal feed at a level of 0.1%.
AB  - For the control of the transmission of bovine spongiform encephalopathy in cattle
      via feedstuff, a real-time polymerase chain reaction assay was developed with
      ruminant-specific Bov-B SINE primers, SYBR Green fluorescence detection, and
      melting curve analysis. In formulated cattle and chicken feed samples spiked with
      pure bovine and sheep meat and bone meal heated at 133 degrees C for 20 min, a
      contamination level of 0.1% was detected.

PMID- 17225590
TI  - Determination of arsenic, cadmium, cobalt, chromium, lead, molybdenum, nickel,
      and selenium in fertilizers by microwave digestion and inductively coupled plasma
      optical emission spectrometry detection: collaborative study.
AB  - There is increasing regulatory interest in the non-nutritive metals content of
      fertilizer materials, but at present there is no consensus analytical method for
      acid digestion and instrument detection of those elements in fertilizer matrixes.
      This lack of method standardization has resulted in unacceptable variability of
      results between fertilizer laboratories performing metals analysis. A method has
      been developed using microwave digestion with nitric acid at 200 degrees C,
      followed by inductively coupled plasma-optical emission spectrometry instrument
      detection, for the elements arsenic, cadmium, cobalt, chromium, molybdenum,
      nickel, lead, and selenium. The method has been collaboratively studied, and
      statistical results are here reported. Fourteen collaborators were sent 62 sample
      materials in a blind duplicate design. Materials represented a broad cross
      section of fertilizer types, including phosphate ore, manufactured phosphate
      products, N-P-K blends, organic fertilizers, and micro-nutrient materials. As
      much as possible within the limit of the number of samples, materials were
      selected from different regions of the United States and the world. Limit of
      detection (LOD) was determined using synthetic fertilizers consisting of reagent
      grade chemicals with near zero levels of the non-nutritive elements, analyzed
      blindly. Samples with high iron content caused the most variability between
      laboratories. Most samples reasonably above LOD gave HorRat values within the
      range 0.5 to 2.0, indicating acceptable method performance according to AOAC
      guidelines for analyses in the mg/kg range. The method is recommended for AOAC
      Official First Action status.

PMID- 17225591
TI  - Quantification of eugenol, luteolin, ursolic acid, and oleanolic acid in black
      (Krishna Tulasi) and green (Sri Tulasi) varieties of Ocimum sanctum Linn. using
      high-performance thin-layer chromatography.
AB  - Ocimum sanctum (family Lamiaceae) is a reputed drug of Ayurveda, commonly known
      as Tulasi. In the present work, we quantified 4 marker compounds, viz., eugenol,
      luteolin, ursolic acid, and oleanolic acid, from the leaf of green and black
      varieties of O. sanctum using high-performance thin-layer chromatography (HPTLC)
      with densitometry. The methods were found to be precise, with relative standard
      deviation (RSD) values for intraday analyses in the range of 0.52 to 0.91%, 0.77
      to 1.29%, 0.11 to 0.16%, and 0.34 to 0.42% and for interday analyses in the range
      of 0.73 to 0.96%, 1.02 to 2.08%, 0.11 to 0.12%, and 0.39 to 0.64% for different
      concentrations of eugenol, luteolin, ursolic acid, and oleanolic acid,
      respectively. Instrumental RSD values were 0.24, 0.39, 0.21, and 0.18% for
      eugenol, luteolin, ursolic acid, and oleanolic acid, respectively. Accuracy of
      the methods was checked by conducting a recovery study at 3 different levels for
      the 4 compounds, and the average recoveries were found to be 99.73, 99.3, 100.58,
      and 100.57%, respectively. Eugenol content ranged from 0.175 to 0.362% (w/w) and
      luteolin from 0.019 to 0.046% (w/w) in the samples analyzed. Green variety was
      found to contain higher amounts of ursolic acid [0.478 and 0.348% (w/w), from
      Sources 1 and 2, respectively] than the black variety [0.252 and 0.264% (w/w)
      from Sources 1 and 2, respectively]. Black variety had 0.174 and 0.218% (w/w) of
      oleanolic acid from Sources 1 and 2, respectively, while it was not detected in
      the green variety. Ursolic acid and oleanolic acid ran at the same Rf value and
      could not be resolved in several solvent systems tried. However, we observed that
      only ursolic acid gave yellow fluorescence under 366 nm ultraviolet light after
      derivatization with anisaldehyde-sulfuric acid reagent. The HPTLC-densitometry
      methods for the quantification of the 4 markers in O. sanctum leaf will have the
      applicability in quality control.

PMID- 17225592
TI  - Headspace gas chromatography-flame ionization detector method for organic solvent
      residue analysis in dietary supplements.
AB  - An analytical method has been developed for the identification and quantification
      of 20 organic solvent residues in dietary supplements. The method utilizes a
      headspace sampler interfaced with gas chromatography and flame ionization
      detection. With split injection (5:1) and a DB-624 column, most of the organic
      solvents are separated in 9 min. The method has been validated and was found to
      be relatively simple and fast, and it can be applied to most common organic
      solvent residues. With the mass detector, the method was able to identify organic
      solvents beyond the 20 standards tested.

PMID- 17225595
TI  - Determination of biotin by high-performance liquid chromatography in infant
      formula, medical nutritional products, and vitamin premixes.
AB  - A solid-phase extraction sample preparation procedure was developed for use with
      a high-performance liquid chromatography (HPLC) method for biotin analysis. The
      HPLC method used a reversed-phase C18 column; chromatography run time was 8.5
      min. After eluting from the column, biotin went through postcolumn reaction to
      form a conjugate with streptavidin-fluorescein isothiocyanate, which was then
      detected by a fluorescence detector. This method was tested with infant formula,
      medical nutritional products, and vitamin premix samples.

PMID- 17225594
TI  - Method for the determination of Aconitum alkaloids in dietary supplements and raw
      materials by reversed-phase liquid chromatography with ultraviolet detection and
      confirmation by tandem mass spectrometry: single-laboratory validation.
AB  - A study of single-laboratory validation (SLV) of a reversed-phase liquid
      chromatography (RP-LC) method was conducted for the determination of diester
      diterpene Aconitum alkaloids, viz., aconitine, mesaconitine, and hypaconitine, in
      a variety of dietary supplements, including single- and multiple-ingredient dry
      powder extracts, pills, capsules, and raw materials. The Aconitum alkaloids in
      the samples were extracted by diethyl ether in the presence of ammonia. After
      cleanup with solid-phase extraction to remove the matrix interferences, the
      alkaloids were determined by RP-LC with UV detection at 235 nm, and the results
      were confirmed by tandem mass spectrometry. The linear responses for aconitine,
      mesaconitine, and hypaconitine based on the present LC system ranged from 0.5 to
      200 microg/mL. Relative standard deviations of 2.0 to 6.9% were obtained from
      duplicate analysis of 6 test materials of different matrixes for the 3 Aconitum
      alkaloids performed by 2 analysts on 5 different days. The recoveries determined
      for supplements and raw materials spiked with 3 Aconitum alkaloids at levels of
      2.5-10 microg/g were in the range of 86-99%. In view of the attainment of
      satisfactory results for accuracy, precision, and recovery in the SLV study, it
      is recommended that the method validation process proceed to a collaborative
      study.

PMID- 17225593
TI  - Preparation and characterization of a suite of ephedra-containing standard
      reference materials.
AB  - The National Institute of Standards and Technology, the U.S. Food and Drug
      Administration, Center for Drug Evaluation and Research and Center for Food
      Safety and Applied Nutrition, and the National Institutes of Health, Office of
      Dietary Supplements, are collaborating to produce a series of Standard Reference
      Materials (SRMs) for dietary supplements. A suite of ephedra materials is the
      first in the series, and this paper describes the acquisition, preparation, and
      value assignment of these materials: SRMs 3240 Ephedra sinica Stapf Aerial Parts,
      3241 E. sinica Stapf Native Extract, 3242 E. sinica Stapf Commercial Extract,
      3243 Ephedra-Containing Solid Oral Dosage Form, and 3244 Ephedra-Containing
      Protein Powder. Values are assigned for ephedrine alkaloids and toxic elements in
      all 5 materials. Values are assigned for other analytes (e.g., caffeine, nutrient
      elements, proximates, etc.) in some of the materials, as appropriate. Materials
      in this suite of SRMs are intended for use as primary control materials when
      values are assigned to in-house (secondary) control materials and for validation
      of analytical methods for the measurement of alkaloids, toxic elements, and, in
      the case of SRM 3244, nutrients in similar materials.

PMID- 17225596
TI  - A validated liquid chromatographic method for estimation of solasodine in various
      Solanum species and market formulations.
AB  - This paper describes an improved liquid chromatographic (LC) method involving a
      prechromatographic derivatization step for the estimation of solasodine from
      berries of various Solanum species, market samples of Solanum xanthocarpum herb,
      extract, and its market formulations. Solasodine has heterocyclic nitrogen but
      has no conjugated double bonds in its structure. However, in all reported LC
      methods, detection was made in the ultraviolet range of 200-213 nm. In the
      present study, a prechromatographic derivatization of solasodine was done by
      forming an ion-pair complex of the heterocyclic nitrogen using the acidic dye
      methyl orange and acetate buffer of pH 4.7. Detection could be made in the
      visible range at 530 nm in this method. The method was validated and successfully
      applied to determine solasodine content in various plant samples and polyherbal
      formulations. The relative standard deviation was found to be 0.025% for system
      precision, and 0.8% for the linearity of the method, and the correlation
      coefficient was 0.999. Plant samples and market formulations were analyzed and
      found to contain solasodine in the range of 0.113-0.227% (w/w) on a fresh weight
      basis in berries; 0.3-1.278% (w/w) and 0.412% (w/w) on a dry weight basis in S.
      xanthocarpum herb powder and extract, respectively; and 0.245-0.525% (w/w) on dry
      weight basis in formulations containing S. xanthocarpum herb powder. No matrix
      interference was encountered. The method was found to be accurate, with a mean
      recovery of 100.5 +/- 0.83%. The method has good reproducibility and was found to
      be suitable for estimation of solasodine.

PMID- 17225597
TI  - Spectrophotometric stability-indicating methods for the determination of
      leflunomide in the presence of its degradates.
AB  - Five simple and sensitive methods were developed for the determination of
      leflunomide (I) in the presence of its degradates 4-trifluoromethyl aniline (II)
      and 3-methyl-4-carboxy isoxazole (III). Method A was based on differential
      derivative spectrophotometry by measuring the delta(1)D value at 279.5 nm. Beer's
      law was obeyed in the concentration range of 2.00-20.00 microg/mL with mean
      percentage accuracy of 100.07 +/- 1.32. Method B depended on first-derivative
      spectrophotometry and measuring the amplitude at 253.4 nm. Beer's law was obeyed
      in the concentration range of 2.00-16.00 microg/mL with mean percentage accuracy
      of 98.42 +/- 1.61. Method C was based on the reaction of degradate (II) with 2,6
      dichloroquinone-4-chloroimide (Gibbs reagent). The colored product was measured
      at 469 nm. Method D depended on the reaction of degradate (II) with para-dimethyl
      aminocinnamaldehyde (p-DAC). The absorbance of the colored product was measured
      at 533.4 nm. Method E utilized 3-methyl-2-benzothiazolinone hydrazone in the
      presence of cerric ammonium sulfate with degradate (II). The green colored
      product was measured at 605.5 nm. The linearity range was 40.00-280.00, 2.40
      24.00, and 30-250 microg/mL with mean percentage accuracy of 100.75 +/- 1.21,
      100.13 +/- 1.45, and 99.74 +/- 1.39 for Methods C-E, respectively. All variables
      were studied to optimize the reaction conditions. The proposed methods have been
      successfully applied to the analysis of leflunomide in pharmaceutical dosage
      forms and the results were statistically compared with that previously reported.

PMID- 17225598
TI  - UV spectrophotometric determination of bioflavonoids from a semisolid
      pharmaceutical dosage form containing Trichilia catigua Adr. Juss and
      Ptychopetalum olacoides Bentham standardized extract: analytical method
      validation and statistical procedures.
AB  - A precise, accurate, and sensitive UV spectrophotometric method was developed and
      validated for routine quantification of total bioflavonoids, expressed as rutin,
      from a topical oil-in-water pharmaceutical emulsion containing the extract of
      Trichilia catigua Adr. Juss and Ptychopetalum olacoides Bentham. The method was
      validated experimentally, and the data were treated rigorously by statistical
      analysis. The following analytical parameters were assessed: linearity,
      specificity, intra- and interrun precision measured as relative standard
      deviation (RSD, %), intra- and interrun accuracy (E, %), recovery (Rec., %),
      limit of detection (LOD, microg/mL), and limit of quantification (LOQ,
      microg/mL). The UV spectrophotometric method was linear (r = 0.9995) for standard
      rutin over the concentration range of 5.0-15.0 microg/mL with specificity for
      total bioflavonoids (expressed as rutin) at 361.0 nm with an absence of
      interferents from the complex matrix; RSD of < or = 1.79%, intrarun (E = 97.88 +/
      1.75 to 99.0 +/- 0.33%) and interrun (E = 98.38 +/- 1.12 to 100.79 +/- 1.30%)
      accuracy; Rec. = 98.64 +/- 0.42 to 100.74 +/- 0.41%; LOD = 0.20 microg/mL; and
      LOQ = 0.30 microg/mL.

PMID- 17225599
TI  - Fractional wavelet analysis for the simultaneous quantitative analysis of
      lacidipine and its photodegradation product by continuous wavelet transform and
      multilinear regression calibration.
AB  - Fractional wavelet transform (FWT) was applied to the original absorption spectra
      of lacidipine (LAC) and its photodegradation product (LACD), and the resulting
      FWT spectra were processed by continuous wavelet transform (CWT) and multilinear
      regression calibration (MLRC) for the simultaneous quantitative analysis of both
      products in their binary mixtures. These methods do not require any chemical
      separation step and chemical complex reaction to obtain a detectable signal for
      the degradation product. By using the Mexican hat function, 2 calibration
      functions for LAC and LACD were obtained by measuring the CWT transformed signals
      at 416.1 nm for LAC and 414.6 nm for LACD, after FWT processing of the original
      absorption spectra. The calibration graphs were linear in the concentration range
      of 5.08-40.64 microg/mL for LAC and 0.51-8.16 microg/mL for LACD. The limit of
      detection and the limit of quantitation were found to be 0.289 and 0.956
      microg/mL for LAC and 0.036 and 0.118 microg/mL for LACD, respectively. For
      comparison, the MLRC algorithm was applied to the linear regression functions for
      the individual drug and its photoproduct. In this approach, a set of linear
      regression functions was obtained from the relationship between concentrations
      and FWT signals in the wavelength range 411.0-412.4 nm. Both methods were applied
      to the quantitative evaluation of LAC and LACD in laboratory and pharmaceutical
      samples, and produced very satisfactory results.

PMID- 17225600
TI  - Validation of a liquid chromatographic method for determination of tacrolimus in
      pharmaceutical dosage forms.
AB  - An accurate, simple, and reproducible liquid chromatographic method was developed
      and validated for the determination of tacrolimus in capsules. The analysis is
      performed at room temperature on a reversed-phase C18 column with UV detection at
      210 nm. The mobile phase is methanol-water (90 + 10) at a constant flow rate of
      0.8 mL/min. The method was validated in terms of linearity, precision, accuracy,
      and specificity by forced decomposition of tacrolimus, using acid, base, water,
      hydrogen peroxide, heat, and light. The response was linear in the range of 0.09
      0.24 mg/mL (r2 = 0.9997). The relative standard deviation values for intra- and
      interday precision studies were 1.28 and 2.91%, respectively. Recoveries ranged
      from 98.06 to 102.52%.

PMID- 17225601
TI  - A selective high-performance liquid chromatography method for the determination
      of reboxetine in bulk drug and tablets.
AB  - Reboxetine is used as a selective noradrenaline reuptake inhibitor for the
      treatment of major depressive disorders. It is effective in the treatment of
      severe depression and safer to use than traditional tricyclic antidepressants. In
      this study, a novel, simple, and rapid stability-indicating high-performance
      liquid chromatography (HPLC) method for reboxetine methansulfonate was
      successfully developed and validated for the assay of tablets. The method was
      used to quantify reboxetine in tablets; it employed a C18 column (150 x 4.6 mm
      id) with an isocratic mobile phase consisting of methanol-phosphate buffer (pH 7,
      0.02 M; 55 + 45, v/v) at a flow rate of 1.0 mL/min. Reboxetine was detected by an
      ultraviolet detector at 277 nm. The retention time of reboxetine was about 4.5
      min. The developed HPLC method was validated with respect to linearity,
      precision, sensitivity, accuracy, and selectivity. The method was linear over the
      concentration range 1-50 microg/mL (r = 0.9999). The limits of detection and the
      quantitation of reboxetine were 0.1 and 0.3 microg/mL, respectively. The relative
      standard deviation values for intraday and interday precision were 0.78-1.01 and
      1.08-1.37%, respectively. Selectivity was validated by subjecting a stock
      solution of reboxetine to neutral, acid, and alkali hydrolysis, as well as
      oxidation, dry heat treatment, and photodegradation. The peaks of the degradation
      products did not interfere with the peak of reboxetine. The results indicated
      that the proposed method could be used in a stability assay. The proposed method
      was successfully applied to the determination of reboxetine in tablets.
      Excipients present in the tablets did not interfere with the analysis.

PMID- 17225602
TI  - A reversed-phase high-performance liquid chromatographic method for the
      determination of zafirlukast in pharmaceutical formulations and human plasma.
AB  - Zafirlukast (ZAF) is a leukotriene receptor antagonist used in the treatment of
      chronic asthma. In this study, a simple and sensitive reversed-phase, high
      performance liquid chromatographic method was developed for the determination of
      ZAF in pharmaceutical formulations and human plasma. Piribedil was used as an
      internal standard. Analysis was carried out on a Nucleosil C18 100 A (150 mm x
      4.6 mm id, 5 Vm) column with acetonitrile-pH 3.0 acetate buffer (70 + 30, v/v) as
      the mobile phase at a flow rate of 0.8 mL/min. The peak was detected by an
      ultraviolet detector set at a wavelength of 240 nm. The retention times were
      about 3.9 min for piribedil and 5.8 min for ZAF. The developed method was applied
      to the determination of ZAF in its pharmaceutical formulation and spiked human
      plasma. For quantification of ZAF in spiked plasma, proteins were precipitated
      with ethanol before chromatographic analysis. The calibration range was linear
      from 49.69-437.50 ng/mL in spiked plasma. The absolute recovery from spiked
      plasma was 98.73 +/- 0.42% at a concentration of 254.78 ng/mL of ZAF. No
      endogenous substances from plasma were found to interfere.

PMID- 17225603
TI  - Spectrofluorometric determination of verapamil hydrochloride in pharmaceutical
      preparations and human plasma using organized media: application to stability
      studies.
AB  - A highly sensitive spectrofluorometric method was developed for the determination
      of verapamil hydrochloride (VP HCl) in pharmaceutical formulations and biological
      fluids. The proposed method is based on investigation of the fluorescence
      spectral behavior of VP HCl in micellar systems, such as sodium dodecyl sulfate
      (SDS) and beta-cyclodextrin (beta-CD). In aqueous solutions of borate buffer of
      pH 9 and 8.5, VP HCI was well incorporated into SDS and beta-CD, respectively,
      with enhancement of its native fluorescence. The fluorescence was measured at 318
      nm after excitation at 231 nm. The fluorescence intensity enhancements were 183
      and 107% in SDS and in beta-CD, respectively. The fluorescence-concentration
      plots were rectilinear over the range of 0.02-0.2 and 0.02-0.25 microg/mL, with
      lower detection limits of 5.58 x 10(-3) and 3.62 x 10(-3) microg/mL in SDS and
      beta-CD, respectively. The method was successfully applied to the analysis of
      commercial tablets and the results were in good agreement with those obtained
      with the official method. The method was further applied to the determination of
      VP HCl in real and spiked human plasma. The mean % recoveries in the case of
      spiked human plasma (n=4) was 92.59 +/- 3.11 and 88.35 +/- 2.55 using SDS and
      beta-CD, respectively, while that in real human plasma (n=3) was 90.17 +/- 6.93
      and 89.17 +/- 6.50 using SDS and beta-CD, respectively. The application of the
      method was extended to the stability studies of VP HCl after exposure to
      ultraviolet radiation and upon oxidation with hydrogen peroxide.

PMID- 17225604
TI  - Feasibility study for the production of certified calibrants for the
      determination of deoxynivalenol and other B-trichothecenes: intercomparison
      study.
AB  - Thirteen European laboratories experienced in the analysis of mycotoxins
      participated in an intercomparison study within a European Commission-funded
      project. Goals of the study were to check the fitness for purpose of a small
      batch of gravimetrically prepared calibrants; to compare individually prepared
      calibrants with common calibrants; to check the feasibility of toxin mixtures as
      calibrant solutions; and to give recommendations on the production of future
      certified reference materials (CRMs) with regard to the nature of the calibrant
      and the means of certification. Each laboratory received ampules of each common
      calibrant containing single toxins [solution containing either deoxynivalenol
      (DON), 3-acetyl-DON (3-Ac-DON), nivalenol (NIV), or 15-acetyl-DON (15-Ac-DON)]
      and 3 ampules of toxin-mixture (solutions of DON + 3-Ac-DON + NIV in
      acetonitrile) of known concentrations (about 20 microg/mL). Ampules with single
      toxins (solution containing either DON, 3-Ac-DON, NIV, or 15-Ac-DON) and a toxin
      mixture (solutions of DON + 3-Ac-DON + NIV in acetonitrile) of unknown
      concentrations were distributed to the participants for quantification. The
      participating laboratories used mainly high-performance liquid chromatography
      (HPLC)-diode array detection UV for DON, 3-Ac-DON, NIV, and 15-Ac-DON; gas
      chromatography-electron capture detection (GC-ECD) and GC-mass spectrometry
      methods were used sparingly. Linear calibration curves were achieved by >90% of
      the participants. Relative between-day variation (RSDr) of 26% of the
      laboratories was greater than the target value of 5% for HPLC, and RSDr of 32% of
      the laboratories was greater than the desired value of 10% for GC. Relative
      between-laboratory variation (RSDR) of the GC results obtained with single common
      calibrants was greater than the target value of 16% for all laboratories. RSDR of
      the HPLC results for the common unknown single toxin solutions was less than the
      target value of 8% except for 15-Ac-DON. Generally, better recoveries were
      observed from common calibrants (102% for mix calibrants and 98% for single
      calibrants) than from individually prepared calibrants (95%). This international
      comparison study clearly showed the high scattering of results in the analysis of
      type-B trichothecenes, particularly when GC was used. Obviously, this
      intercomparison study was not suited for the certification of B-trichothecenes. A
      certification of the proposed calibrant material was therefore recommended on the
      basis of its gravimetrical preparation.

PMID- 17225605
TI  - A novel correlation for rapid lactose determination in milk by a cryoscopic
      technique.
AB  - Residual lactose in special milk was systematically determined for people with
      lactose intolerance by means of a rapid on-line measurement of the cryoscopic
      point. A proposed cryoscopic procedure was compared to 2 conventional yet highly
      laborious methods: the enzymatic procedure with spectrophotometric control and
      the polarimetric method. Several experiments with different mixtures of both semi
      skimmed and low-lactose milk were performed. A lineal relationship was found
      between lactose concentration and freezing point, the analytical equation for
      which shows a close relationship regarding the 3 methods used. The advantages of
      the cryoscopic procedure include speed in obtaining results and operational
      simplicity at a low cost, better monitoring of enzymatic hydrolysis kinetics, and
      greater control over the production process for delactosed milk. The equation
      obtained also enables prediction of the lactose percentage in commercial milk by
      a simple measurement of freezing point.

PMID- 17225606
TI  - Determination of the moisture content of instant noodles: interlaboratory study.
AB  - Determination of the moisture content of instant noodles, currently under
      discussion by the Codex Alimentarius Commission (CAC) requires 2 methods: one for
      fried noodles and the other for nonfried noodles. The method to determine the
      moisture content of fried noodles by drying at 105 degrees C for 2 h used in the
      Japanese Agricultural Standard (JAS) system of Japan can be applied to this
      purpose. In the present study, the JAS method for fried noodles was modified to
      be suitable for nonfried noodles by extending the drying time to 4 h. An
      interlaboratory study was conducted to evaluate interlaboratory performance
      statistics for these 2 methods. Ten participating laboratories each analyzed 5
      test materials of fried and nonfried noodles as blind duplicates. After removal
      of outliers statistically, the repeatability (RSDr) and the reproducibility
      (RSD(R)) of these methods were 1.6-2.6 and 3.9-4.8% for fried noodles, and 0.3
      1.5 and 1.3-2.9% for nonfried noodles, respectively.

PMID- 17225607
TI  - Rapid determination and confirmation of biogenic amines in tuna loin by gas
      chromatography/mass spectrometry using ethylchloroformate derivative.
AB  - A gas chromatography-mass spectrometry (GC/MS) method is described for the easy
      rapid determination and simultaneous confirmation of the biogenic amines
      putrescine (PUT), cadaverine (CAD), histamine (HTA), and spermidine (SPD) in
      fresh frozen tuna loin. The method can also be used to monitor tyramine (TYR).
      The method involves homogenization of fish tissue, extraction of biogenic amines
      into trichloroacetic acid solution, centrifugation, alkalization, and
      derivatization of supernatant with ethylchloroformate. All seafood species were
      fortified to contain 2.5, 5.0, 10.0, 12.5, and 25.0 microg/g (ppm) PUT, CAD, and
      SPD; and 10.0, 20.0, 40.0, 50.0, and 100.0 microg/g (ppm) HTA. Determination was
      based on standard curves for each analyte using peak areas with matrix standards
      equivalent to a concentration range bracketing the spike level. A set of 5 matrix
      controls (unfortified tuna tissue) was also analyzed; only endogenous SPD was
      found in all samples. The interassay average recoveries ranged from 57 to 79%
      across analytes and spike levels.

PMID- 17225608
TI  - Interlaboratory evaluation of two enzyme-linked immunosorbent assay kits for the
      detection of egg, milk, wheat, buckwheat, and peanut in foods.
AB  - The labeling of 5 major allergenic ingredients (egg, milk, wheat, buckwheat, and
      peanut) is mandatory in Japan, and 2 series of enzyme-linked immunosorbent assay
      (ELISA) kits have been established as official screening methods. However, these
      official methods have not provided the necessary sensitivity, due in part to poor
      extraction efficiency. To address this need, 2 novel ELISA kits have been
      developed: the FASTKIT ELISA Ver. II Series and the FASPEK Allergenic Substances
      Detection Kit. The new kit systems use an improved extraction buffer that can
      extract insoluble proteins produced by processing and feature new antibodies that
      bind to the denatured proteins extracted with the new extraction buffer. The
      analytical performances of the 2 new ELISA kit series were evaluated in an
      interlaboratory study. Ten laboratories participated in the study and determined
      the major allergenic ingredients contained in 5 types of model processed food.
      The 2 ELISAs displayed fairly good reproducibility and sufficient recovery.

PMID- 17225609
TI  - Determination of nucleic acids using fluorescence probe sensitized by
      microemulsion.
AB  - Because the fluorescence of azur A can be quenched by adding nucleic acid, a
      sensitive fluorometric method for determination of nucleic acids at nanogram
      levels was established. Using optimal conditions, the calibration curves were
      linear in the range of 0-6.0 microg/mL for calf thymus deoxyribonucleic acid (ct
      DNA) and 0-7.0 microg/mL for herring sperm DNA (hs DNA). The limits of
      determination were 3.5 and 3.8 ng/mL, respectively, which shows the high
      sensitivity of this method. Triton X-100 microemulsion was applied as a sensitive
      media to enhance the sensitivity. The binding mode concerning the interactions of
      azur A with nucleic acids was also studied and the association constant with
      different binding numbers was obtained. The method has been applied to the
      determination of nucleic acid in both synthetic and real samples, such as
      cauliflower and pork liver, with satisfactory results.

PMID- 17225610
TI  - Quantitative assessment of hard surface disinfectant activity against the
      foodborne pathogen Listeria monocytogenes.
AB  - Listeria monocytogenes is an important foodborne pathogen that must be controlled
      to ensure food safety. For the years 2003 and 2004, L. monocytogenes caused 20
      deaths per 100 listeriosis cases and was responsible for most food recalls for
      pathogen contamination. The objective of this work was to develop a quantitative
      method to assess disinfectant activity against L. monocytogenes. Standard
      procedures for testing disinfectants against 3 bacteria are described in the AOAC
      Official Methods of Analysis as use-dilution methods. No standard methods are
      provided for L. monocytogenes. In this study, preliminary efficacy of a
      quaternary ammonium compound with hydroperoxide ion was determined for 25
      bacterial strains. The zones of inhibition ranged from 7.0 to 12.5 mm, and the
      minimum inhibitory concentration ranged from 5 to 250 ppm. For final efficacy,
      stainless steel carriers were contaminated with L. monocytogenes and tested
      separately for 5, 10, and 15 min in disinfectant or phenol. After exposure, the
      carriers were placed into 2 series of D/E neutralization broth. For 3
      replications with duplicate samples, the phenol coefficient was 3.3. This
      research presents a technique-sensitive method that provides quantitative data
      for comparison and analysis of disinfectant activity against L. monocytogenes.

PMID- 17225611
TI  - Method modification (2004.08) to field testing of visible powders on a variety of
      nonporous environmental surfaces: field study.
AB  - The RAMP Anthrax Test Cartridge for detecting Bacillus anthracis was validated
      for use in the field for detection of B. anthracis spores in visible powder
      residues on 7 nonporous environmental surfaces. Six teams of trained first
      responders and civil support personnel in Class C personal protective equipment
      sampled visible powder residues on plastic, stainless steel, ceramic tile, wood,
      rubber, sealed concrete, and food-grade painted wood and analyzed the samples on
      the RAMP Anthrax Test System. The accuracy for each surface was at least 97% and
      the overall average was 98.8%. The overall average false-positive rate was 1.79%
      and false-negative rate was 1.07% for all surfaces. There were no significant
      differences between surfaces or between spore levels.

PMID- 17225612
TI  - Enumeration procedure for monitoring test microbe populations on inoculated
      carriers in AOAC use-dilution methods.
AB  - The AOAC Use-Dilution methods do not provide procedures to enumerate the test
      microbe on stainless steel carriers (penicylinders) or guidance on the expected
      target populations of the test microbe (i.e., a performance standard). This
      report describes the procedures used by the U.S. Environmental Protection Agency
      to enumerate the test microbe (carrier counts) associated with conducting the Use
      Dilution method with Staphylococcus aureus (Method 955.15) and Pseudomonas
      aeruginosa (Method 964.02) and the examination of historical data. The carrier
      count procedure involves the random selection of carriers, shearing bacterial
      cells from the carrier surface through sonication, and plating of serially
      diluted inoculum on trypticase soy agar. For each Use-Dilution test conducted,
      the official AOAC method was strictly followed for carrier preparation, culture
      initiation, test culture preparation, and carrier inoculation steps. Carrier
      count data from 78 Use-Dilution tests conducted over a 6-year period were
      compiled and analyzed. A mean carrier count of 6.6 logs (approximately 4.0 x
      10(6) colony-forming units/carrier) was calculated for both S. aureus and P.
      aeruginosa. Of the mean values, 95% fell within +/- 2 repeatability standard
      deviations. The enumeration procedure and target carrier counts are desirable for
      standardizing the Use-Dilution methods, increasing their reproducibility, and
      ensuring the quality of the data.

PMID- 17225613
TI  - Determination of forchlorfenuron residues in watermelon by solid-phase extraction
      and high-performance liquid chromatography.
AB  - A method using solid-phase extraction for cleanup, followed by high-performance
      liquid chromatography with ultraviolet detection (HPLC/UV), was developed for the
      determination of forchlorfenuron residues in watermelon. The pesticide is
      extracted from the sample with acidic acetonitrile, and the extract is loaded
      onto a primary-secondary amine (PSA) column. The pesticide is eluted with acetone
      and determined by HPLC/UV. The PSA column was found to provide effective cleanup,
      removing the greatest number of sample matrix interferences. The acetonitrile
      extraction followed by the PSA cleanup provided recoveries of >95%, coefficients
      of variation (precision) of <10%, and sensitivity of 0.005 mg/kg, in agreement
      with the directives for method validation in residue analysis. The proposed
      method was successfully used to determine forchlorfenuron residue levels and
      dissipation rates in watermelon grown in an experimental greenhouse in Beijing,
      People's Republic of China.

PMID- 17225614
TI  - Determination of spinosad in vegetables and fruits by high-performance liquid
      chromatography with UV and mass spectrometric detection after gel permeation
      chromatography and solid-phase extraction cleanup on a 2-layered column.
AB  - A simple and reliable method was developed for the determination of spinosyns A
      and D, the active ingredients of spinosad, in vegetables and fruits, by high
      performance liquid chromatography with UV detection (HPLC-UV) and confirmation by
      mass spectrometry (MS); the method uses selected gel permeation chromatography
      (GPC) and a 2-layered column for solid-phase extraction system. An aliquot of the
      crude sample extract obtained by acetonitrile extraction is loaded into the GPC
      system. The fraction containing spinosyns A and D is selectively collected and
      loaded directly onto a 2-layered column consisting of graphitized carbon (upper
      layer) and cyclohexyl-bonded silica gel (lower layer). After the column is washed
      with the GPC mobile phase acetone-cyclohexane (3 + 7), the column is eluted with
      acetonitrile containing 2% triethylamine. The eluate is used for HPLC-UV/MS
      analysis. Average recoveries from fortified cabbage, green perilla, fig, and
      strawberry at analyte concentrations of 0.05 and 0.25 microg/g were >85%, and the
      relative standard deviations were <9%. The detection limits for spinosyns A and D
      in green perilla were 0.005 microg/g by UV detection and 0.001 microg/g by MS
      detection.

PMID- 17225615
TI  - Determination of semicarbazide in fresh egg and whole egg powder by liquid
      chromatography/tandem mass spectrometry: interlaboratory validation study.
AB  - An interlaboratory validation study was conducted according to harmonized
      protocols to evaluate the effectiveness of a liquid chromatography/tandem mass
      spectrometry (LC/MS/MS) method for the determination of semicarbazide (SEM) in
      fresh whole egg and in an industrially processed whole egg powder. The sample was
      extracted with hydrochloric acid and derivatized with 2-nitrobenzaldehyde, with
      1,2-[(15)N2(13)C]SEM as the internal standard. The extract was neutralized and
      purified on a solid-phase extraction cartridge. SEM was determined by reversed
      phase LC with detection by MS/MS. Five fresh egg samples, of which 3 were
      obtained from hens fed nitrofurazone (NFZ), one was spiked with SEM at 50
      microg/kg and one was a blank sample, and 5 industrial whole egg powder samples,
      of which 3 were spiked with fresh whole egg from hens fed NFZ, one was spiked
      with SEM at 350 microg/kg, and one was a blank sample, were sent to 15
      laboratories in 10 different European countries. Results were obtained from 12
      participants. Average recoveries of SEM from the fresh egg and the egg powder
      samples were 105.3 and 121.3%, respectively. The relative standard deviation for
      repeatability (RSDr) ranged from 2.9 to 9.3%, and the relative standard deviation
      for reproducibility (RSDR) ranged from 22.5 to 38.1%. The method showed
      acceptable within- and between-laboratory precision for both matrixes, as
      evidenced by the HorRat values, at the target levels for the determination of
      SEM.

PMID- 17225616
TI  - Liquid chromatography/fluorescence method for emamectin B1a and desmethylamino
      emamectin B1a residues in lobster tissue.
AB  - A liquid chromatography (LC)/fluorescence procedure was validated for emamectin
      (EM B1a) and desmethylamino-emamectin (DMAEM B1a) residues in lobster tissue.
      They were extracted by shaking and sonicating with 1% ammonium acetate-methanol
      in the presence of sand. The extract was concentrated, partitioned with ethyl
      acetate, and cleaned up on a propylsulfonic cation exchange cartridge. The
      analytes were eluted from the cartridge with 5% ammonium hydroxide-methyl
      acetate, the eluate was concentrated, and the solvent was changed to dry 20%
      ethyl acetate-acetonitrile before derivatization with trifluoroacetic anhydride-N
      methylimidizole. The products were analyzed by LC-fluorescence, and no
      interference [>limit of detection (LOD)] was detected in the control samples.
      Lobster tissues fortified with EM B1a and DMAEM B1a at 0.5, 5, 10, 25, and 50
      ng/g gave overall mean recoveries of 96.7 +/- 12.4%, relative standard deviation
      (RSD) = 12.8% for EM B1 and 83.6 +/- 12.1%, RSD = 14.5% for DMAEM B1a. Regression
      analysis of the calibration data gave slopes of 0.90 (EM B1a) and 0.71 (DMAEM
      B1a) with an r2 = 0.99 for both compounds. The calculated LOD and limit of
      quantification (LOQ) for EM B1a were 1.10 and 3.32 ng/g, respectively, and for
      DMAEM B1a were 0.762 and 2.31 ng/g, respectively. Residues of EM B1a and DMAEM
      B1a in fortified lobster tissues stored at -20 degrees C showed that residues
      were stable for 10-12 months. No loss of EM B1a and DMAEM B1a residues was
      observed after 3 freeze/thaw cycles of fortified tissue in a 5-day period.

PMID- 17225618
TI  - Committee on microbiology and extraneous materials.

PMID- 17225617
TI  - Multiresidue determination of zeranol and related compounds in bovine muscle by
      gas chromatography/mass spectrometry with immunoaffinity cleanup.
AB  - A gas chromatography/mass spectrometry (GC/MS) method with immunoaffinity cleanup
      was developed for the determination of zeranol and related compounds, taleranol,
      zearalanone, and alpha-zearalenol in bovine muscle. Muscle samples were extracted
      with methanol and cleaned up with immunoaffinity chromatography (IAC) columns
      containing monoclonal antibodies raised against zeranol coupled to CNBr-activated
      Sepharose 4B. After derivatization, the compounds were analyzed by GC/MS. The
      dynamic column capacities for zeranol, taleranol, zearalanone, and alpha
      zearalenol were 2639.7, 2840.3, 2731.5, and 2736.3 ng/mL Sepharose gel,
      respectively. The limits of detection and quantification were 0.5 and 1.0 ng/g,
      respectively, for all 4 compounds. Mean recoveries were 79.6-110.7% with
      coefficients of variation of 3.2-11.4% at spiked levels of 1.0-5.0 ng/g. This IAC
      GC/MS method may be used for the determination of zeranol, taleranol,
      zearalanone, and alpha-zearalenol residues in bovine muscle, and possibly other
      tissues.

PMID- 17225619
TI  - Risk and security in childbirth.
AB  - Risk and security are often defined as being complementary. Security is based on
      risk calculations, which undergo constant change. An increasing number of
      abnormalities can be uncovered in the human body, and more and more people are
      defined as being at risk for various diseases or at risk as child bearers. The
      aim of this paper is to examine the notion of risk, and to understand it in
      different ways as it is applied to childbirth. General and professional
      perspectives on risk are different; views vary as to what constitutes acceptable
      risk, and the association between normalcy and complications is socially and
      culturally determined. Figures for risk and reliability are not objective values.
      The safe and the risky are anchored in certain symbol systems. Alternative and
      dialogic notions have been introduced in conversations and thinking about risk,
      and medicalism and paternalism have been questioned. This questioning has thus
      far had little influence on clinical practice. The two opposite perspectives of
      risk and security in the area of pregnancy and birth should be taken into
      consideration. The childbearing woman has preferences of her own. Dialog with the
      health professional and information about professional facts and professional
      uncertainty should be offered.

PMID- 17225620
TI  - Psychological well-being improves in women with breast cancer after treatment
      with applied relaxation or electro-acupuncture for vasomotor symptom.
AB  - The aim of this study was to evaluate the effect of applied relaxation and
      electro-acupuncture (EA) on psychological well-being in breast cancer-treated
      women with vasomotor symptoms. Thirty-eight breast cancer-treated postmenopausal
      women with vasomotor symptoms were included in the study. They were randomized to
      either treatment with electro-acupuncture (EA) (n = 19, three of them with
      tamoxifen) or applied relaxation (AR) (n = 19, five of them with tamoxifen) over
      a 12-week study period with six months follow-up. Vasomotor symptoms were
      registered daily. A visual analog scale was used to assess climacteric symptom,
      estimation of general well-being was made using the Symptom Checklist, and mood
      using the Mood Scale. These were applied during treatment and at follow-up. In
      total 31 women completed 12 weeks of treatment and six months of follow-up. Hot
      flushes were reduced by more than 50%. Climacteric symptoms significantly
      decreased during treatment and remained so six months after treatment in both
      groups. Psychological well-being significantly improved during therapy and at
      follow-up visits in both groups. Mood improved significantly in the electro
      acupuncture treated group. In conclusion psychological well-being improved in
      women with breast cancer randomized to treatment with either AR or EA for
      vasomotor symptoms and we therefore suggest that further studies should be
      performed in order to evaluate and develop these alternative therapies.

PMID- 17225621
TI  - Premenstrual dysphoric disorder: prevalence, diagnostic considerations, and
      controversies.
AB  - Premenstrual dysphoric disorder (PMDD) has been included as a formal diagnosis of
      a mood disorder in the appendix of the Diagnostic and Statistical Manual of
      Mental Disorders, 4th edition in 1994. The ensuing, critical attention has
      resulted in increased research productivity and clinical recognition of this
      neglected women's health problem. A decade later, this paper will review the
      current literature on PMDD focusing on prevalence, biopsychosocial etiological
      correlates, history of the development of a formal DSM diagnosis, and the
      controversies surrounding the current classification of PMDD. The authors
      conclude that PMDD presents a distinct diagnostic entity and that recognition
      through formal diagnostic criteria serves the important minority of women who
      suffer from this cyclical mood disorder distinct from premenstrual symptoms and
      major depression.

PMID- 17225622
TI  - Memory of childbirth in the second year: the long-term effect of a negative birth
      experience and its modulation by the perceived intranatal relationship with
      caregivers.
AB  - OBJECTIVE: To assess the memory of various subdimensions of the birth experience
      in the second year postpartum, and to identify women in the first weeks
      postpartum at risk of developing a long-term negative memory. DESIGN, METHOD,
      OUTCOME MEASURES: New mothers' birth experience (BE) was assessed 48-96 hours
      postpartum (T1) by means of the SIL-Ger and the BBCI (perception of intranatal
      relationships); early postnatal adjustment (week 3 pp: T1(bis)) was also
      assessed. Then, four subgroups of women were defined by means of a cluster
      analysis, integrating the T1/T1(bis) variables. To evaluate the memory of the BE,
      the SIL-Ger was again applied in the second year after childbirth (T2). First,
      the ratings of the SIL-Ger dimensions of T1 were compared to those at T2 in the
      whole sample. Then, the four subgroups were compared with respect to their
      ratings of the birth experience at T2 (correlations, ANOVAs and t-tests).
      RESULTS: In general, fulfillment, emotional adaptation, physical discomfort, and
      anxiety improve spontaneously over the first year postpartum, whereas in negative
      emotional experience, control, and time-going-slowly no shift over time is
      observed. However, women with a negative overall birth experience and a low level
      of perceived intranatal relationship at T1 run a high risk of retaining a
      negative memory in all of the seven subdimensions of the birth experience.
      CONCLUSIONS: Women at risk of developing a negative long-term memory of the BE
      can be identified at the time of early postpartum, when the overall birth
      experience and the perceived intranatal relationship are taken into account.

PMID- 17225623
TI  - Patients' satisfaction with laparoscopic myomectomy.
AB  - BACKGROUND: Laparoscopic myomectomy offers a uterus-conserving alternative to
      hysterectomy for patients suffering from symptomatic myomas. The following study
      aimed to examine clinically relevant aspects of perceived satisfaction following
      laparoscopic myomectomy. METHOD: 191 women completed a 17-item questionnaire on
      retrospective satisfaction with their choice for the operation and with the
      surgical outcome (e.g., "all myomas were removed", "termination of discomfort").
      A comparison was performed using questionnaire data, patients' demographical data
      and surgical records (e.g., duration of surgery). RESULTS: Women who trusted in
      their decision for the surgical procedure revealed better surgical outcome and
      greater satisfaction with the treatment process than those who were insecure with
      their choice. Age did not influence the patients' perceived satisfaction. In
      anticipation of the surgical outcome, patients placed stronger emphasis on tissue
      preservation than on their wish for a child or on the termination of discomfort.
      CONCLUSIONS: The high overall level of satisfaction and positive outcome in
      various age groups contradicts current recommendations against laparoscopic
      myomectomy for women over 40 years of age.

PMID- 17225624
TI  - Psychosocial factors and mode of delivery.
AB  - Childbirth is a substantial physical and emotional endeavor. Because emergency
      Cesarean and instrumental vaginal delivery impose a greater mortality and
      physical and emotional morbidity on both the mother and the infant than normal
      vaginal delivery, it is important to identify factors that are associated with
      the risk of operative delivery. In previous investigations, some associations
      have been found, but the effect of psychosocial factors is not clear. In this
      study we examined several factors which could be associated with the risk for
      instrumental and surgical delivery. In addition to biomedical factors we included
      psychosocial factors such as depressive symptoms, quality of the relationship of
      the woman with her partner, personality, lifestyle and educational level. We
      assessed 354 healthy nulliparous pregnant women with a child in vertex
      presentation and spontaneous onset of term labor using validated questionnaires.
      We found that social support from the woman's partner in pregnancy, lack of
      depressive symptoms and specific personality traits are not protective against
      instrumentally assisted vaginal delivery or emergency Cesarean section.
      Predictive factors for operative delivery after spontaneous onset of labor are
      higher fetal weight, non-occiput anterior presentation and advanced gestational
      age, and foremost fetal distress during parturition.

PMID- 17225625
TI  - Girls experiencing sexual intercourse early: could it play a part in reproductive
      health in middle adulthood?
AB  - The aim of the present study is to examine the possible relationship between
      experiencing early intercourse and reproductive health characteristics in midlife
      for women. The participants belonged to the Swedish longitudinal research program
      Individual Development and Adaptation (IDA) project. By the age of 14, the cohort
      consisted of 590 girls, whereas 522 gave information about the timing of their
      first sexual intercourse experience. Approximately 29 years later, when the women
      were 43 years old, a sub-cohort of 369 women participated in the psychological
      medical investigation. Those who experienced early intercourse were likely to be
      different on various demographics and have markers of poorer reproductive health
      characteristics than their counterparts. More specifically, those experiencing
      early intercourse were less formally educated, left home earlier, and earned on
      average less than their counterparts who experienced sexual intercourse later.
      Early intercourse likely plays a role in not only specific reproductive health
      but also reproductive health characteristics as a whole in midlife. Early
      intercourse was consistently a predictor of teenage pregnancy, terminated
      pregnancies, no use of contraception, and having menstrual symptoms.

PMID- 17225626
TI  - The psychological effects of stillbirth and neonatal death on fathers: systematic
      review.
AB  - OBJECTIVE: To review the available evidence on the psychological effects of
      perinatal death on fathers. METHOD: Electronic search of CINAHL, MEDLINE and
      PsycINFO databases from 1966-2005. INCLUSION CRITERIA: papers describing at least
      one psychological outcome for fathers who had experienced stillbirth or neonatal
      death. EXCLUSION CRITERIA: papers not in English, dissertations, reviews, books
      without original data, intervention studies, studies of parents without separate
      results for fathers, studies where perinatal loss was not distinguished from
      other losses, first person accounts of a single experience, studies reporting on
      fewer than five fathers. Seventy-seven potential papers were obtained and
      screened by two authors. Seventeen studies were included. Study quality was rated
      using a checklist and main findings were summarized. RESULTS: Quality of
      methodology varied. Qualitative studies described classical grief responses, but
      less guilt than mothers. Fathers described experiences related to their social
      role and potential conflict between grieving couples. Quantitative research
      reported symptoms of anxiety and depression, but at a lower level than mothers.
      Fathers may develop post-traumatic stress disorder following stillbirth.
      DISCUSSION: Case prevalence of psychological disorders is unknown. More good
      quality research is needed. The social role of fathers as carers for their
      partners needs recognition when planning care for bereaved families.

PMID- 17225627
TI  - Psychological and physical factors influencing the health-related quality of life
      of patients of a department of gynecology in a university hospital.
AB  - The aim of our study was to assess the physical and mental quality of life of in
      patients of a Gynecological University Hospital and the factors influencing the
      quality of life. 715 women, who were treated in hospital with non-malignant or
      malignant gynecological or obstetrical diseases, took part in the study. Besides
      demographical data and relevant medical parameters the quality of life (SF-12),
      anxiety and depression (HADS) as well as physical discomforts (GBB) were
      assessed. The physical quality of life of the study population was significantly
      lower than that of the normal population (p < 0.001). Patients with obstetric
      diseases in comparison with patients with malignant gynecological and other
      gynecological diseases had the lowest physical quality of life. Regarding the
      mental factor, patients with malignant gynecological diseases feel most impaired,
      followed by those with other gynecological and obstetrical conditions. The
      multivariate analysis of the quality of life showed that up to 60% of the
      variance could be explained. The lowest variance elucidation was found in
      obstetrical patients in whom the physical complaints elucidated only a small part
      of the variance. Our results show on the one hand the high impairment of mental
      and especially of physical quality of life in women who are in hospital with
      gynecological or obstetrical diseases. On the other hand they show the great
      significance of the quality of life as an outcome parameter. These findings
      should be considered in gynecological in-patient treatments by using integrated
      psychosomatic care.

PMID- 17225628
TI  - Validation of the Edinburgh Postnatal Depression Scale as a screening tool for
      depression in late pregnancy among Nigerian women.
AB  - This study aimed to examine the validity of the Edinburgh Postnatal Depression
      Scale (EPDS) as a screening tool for depression in late pregnancy among Nigerian
      women. A total of 182 women in late pregnancy (32-36 weeks) completed either the
      English or the translated Yoruba language version of the EPDS and a proportion of
      them were then assessed for the presence of DSM-IV major and minor depressive
      disorders using the MINI International Neuropsychiatric Interview. A cut-off
      score of 10 on the EPDS was found to be the best for screening for both major and
      minor depression (sensitivity = 0.867, specificity = 0.915, Diagnostic Likelihood
      Ratio for a positive result = 10.200). When screening for major depression only,
      a cut-off of 12 was found to the most appropriate (sensitivity = 1.000,
      specificity = 0.961, Diagnostic Likelihood Ratio for a positive result = 25.641).
      The EPDS is a valid and useful instrument in screening for depression in late
      pregnancy among Nigerian women.

PMID- 17225629
TI  - Initiative shines spotlight on real-world models for diabetes care in diverse
      populations.

PMID- 17225630
TI  - Hospital offers DM-style programs that physicians embrace.
AB  - A DM model appeals to physicians. DM providers and physicians do not always see
      eye-to-eye when it comes to patient care, but a unique, hospital-funded effort in
      Middlesex County, CT, is getting high marks for the smooth working relationship
      it has forged between the nurse managers who drive the DM interventions and the
      providers who send them patients.

PMID- 17225631
TI  - New-age PHR comes with decision-support, multiple opportunities for DM.
AB  - New-age PHRs aim to uncover opportunities for quality improvement. Health plans
      have been scrutinizing administrative data for years, but thus far have not
      offered such analysis to patients or providers. Doing so is just part of the
      package that will soon be made available to the customers of Manhattan, NY-based
      ActiveHealth Management through Web-based personal health records. The approach
      is designed to get patients more involved in their own care, facilitating
      analysis of not just claims data, but patient-reported data as well.

PMID- 17225632
TI  - Pharmaceutical companies and health plans have a shared interest in boosting
      medication adherence.
AB  - Health plans and pharmaceutical companies develop adherence strategies. With only
      about half of all prescriptions being taken as directed, both health plans and
      pharmaceutical companies are getting serious about developing strategies to keep
      patients on track with their medications. What they're finding is that it's a
      complicated problem requiring patient-centric solutions.

PMID- 17225633
TI  - An examination of twenty literacy, science, and mathematics practices used to
      educate students who are deaf or hard of hearing.
AB  - The results of a multistep process to begin identifying best practices in deaf
      education are presented. To identify current practices, a survey was conducted of
      the literature, the Web sites of professional organizations, and states'
      education Web sites, which yielded a number of commonly discussed practices. Ten
      of the more highly cited practices in literacy instruction and 10 of the more
      highly cited practices in science and mathematics instruction were identified for
      additional scrutiny. Hundreds of articles were examined to identify research
      support for the 20 identified practices. Some practices had adequate research
      support; others had minimal support. The authors identify each of the 20
      practices, describe the practice, present a summary of the literature that was
      examined, and rate the usefulness of the knowledge base relative to a "best
      practice" designation.

PMID- 17225634
TI  - Master teachers' responses to twenty literacy and science/mathematics practices
      in deaf education.
AB  - Under a grant to improve outcomes for students who are deaf or hard of hearing
      awarded to the Association of College Educators--Deaf/Hard of Hearing, a team
      identified content that all teachers of students who are deaf and hard of hearing
      must understand and be able to teach. Also identified were 20 practices
      associated with content standards (10 each, literacy and science/mathematics).
      Thirty-seven master teachers identified by grant agents rated the practices on a
      Likert-type scale indicating the maximum benefit of each practice and maximum
      likelihood that they would use the practice, yielding a likelihood-impact
      analysis. The teachers showed strong agreement on the benefits and likelihood of
      use of the rated practices. Concerns about implementation of many of the
      practices related to time constraints and mixed-ability classrooms were themes of
      the reviews. Actions for teacher preparation programs were recommended.

PMID- 17225635
TI  - Assessment practices of professionals serving students who are deaf or hard of
      hearing: an initial investigation.
AB  - Assessment currently plays a critical role in American schools and society, in
      tasks ranging from ranking schools' effectiveness, to determining individual
      placement, to planning instruction. The purpose of the study was to gather data
      about the formal and informal assessment instruments and processes used by
      professionals in deaf education. Respondents indicated that statewide annual
      assessments are the most frequently used measures, followed by the Stanford
      Achievement Test series and the Woodcock-Johnson III Test of Achievement.
      Commonly used assessment instruments and procedures for each academic area are
      reported in rank order. Issues about current practices are raised, and
      suggestions for additional research related to assessment practices in deaf
      education are provided.

PMID- 17225636
TI  - Oxford House: deaf-affirmative support for substance abuse recovery.
AB  - Deaf individuals seeking substance abuse recovery are less likely to have access
      to treatment and aftercare services because of a lack of culturally and
      linguistically specific programs and insufficient information about existing
      services. Previous research indicates that Oxford House, a network of resident
      run recovery homes, serves a diverse group of individuals in recovery. However,
      research has not addressed the experiences of Deaf Oxford House residents. The
      present study found no significant differences between Deaf and hearing men
      living in Oxford House in terms of sense of community and abstinence self
      efficacy. However, while most of the hearing participants were employed, none of
      the Deaf Oxford House members were. The study's findings indicate that Oxford
      House may be a promising Deaf-affirmative alternative for individuals seeking
      recovery from substance abuse. However, since Oxford Houses are self-supporting,
      Oxford Houses designed for the Deaf community may face unique economic
      challenges.

PMID- 17225637
TI  - Sign language Web pages.
AB  - The WORLD WIDE WEB has changed the way people interact. It has also become an
      important equalizer of information access for many social sectors. However, for
      many people, including some sign language users, Web accessing can be difficult.
      For some, it not only presents another barrier to overcome but has left them
      without cultural equality. The present article describes a system that allows
      sign language-only Web pages to be created and linked through a video-based
      technique called sign-linking. In two studies, 14 Deaf participants examined two
      iterations of signlinked Web pages to gauge the usability and learnability of a
      signing Web page interface. The first study indicated that signing Web pages were
      usable by sign language users but that some interface features required
      improvement. The second study showed increased usability for those features;
      users consequently couldnavigate sign language information with ease and
      pleasure.

PMID- 17225638
TI  - Is there a link between hearing aid use, employment, and income?
AB  - This paper examines hearing aid use by 60 congenitally deaf individuals who
      attended special education units in South Australia. The study indicates that
      only one-third to half of deaf adults wore their hearing aids in social
      situations for speech detection. Just over one-third (n = 22) of the deaf adults
      involved in this study wore their hearing aids at work and less than half (n =
      27) wore their hearing aids at home. Younger deaf adults were more likely to wear
      their hearing aids in the home than older deaf adults. Younger deaf adults tended
      to wear their hearing aids more frequently when they were at school if they had
      perceived their teachers had a positive attitude to deafness. This study found
      that there was no statistically significant relationship between wearing hearing
      aids and employment status. There was also no statistically significant
      difference in hearing aid use between men and women. The low use of hearing aids
      could be attributed at least in part to the current Australian policy regarding
      supply and servicing of hearing aids to congenitally deaf individuals which
      ceases to be free after the individual reaches 21 years of age.

PMID- 17225640
TI  - Visual phonics: an English code buster?
AB  - Visual phonics is an instructional program to provide print awareness, alphabet
      knowledge, and sound-letter correspondence for children with hearing loss who
      experience difficulty developing a foundation of phonemic awareness skills. Its
      purpose is "to clarify the sound symbol relationship between spoken English and
      print" (Waddy-Smith & Wilson, 2003, p. 15). It is implemented in numerous school
      districts, particularly in California and Florida, and can be learned in a 2-day
      workshop. Administrators, teachers, and speech pathologists see potential benefit
      in using Visual Phonics to help students with hearing loss raise their
      achievement scores in reading and spelling. However, it is critical to note that
      Visual Phonics has virtually no research base. Researchers, teachers, and speech
      pathologists are called upon to collect their data and begin research on the
      effectiveness of Visual Phonics. This is a case in which the research-to-practice
      gap must be closed.

PMID- 17225639
TI  - Is tobacco use a problem among deaf college students?
AB  - College students' tobacco use poses a significant public health problem.
      Effective intervention requires understanding of this behavior among race/ethnic,
      cultural, and linguistic collegiate subgroups, including deaf and hard of hearing
      collegians. Findings from a first-ever tobacco-related survey among this
      understudied population are reported. The authors used written questionnaires and
      the Interactive Video Questionnaire, a multimedia computer technology developed
      for use with the deaf and hard of hearing, to interview 241 volunteers on seven
      California college campuses. They found lower self-reported current smoking
      prevalence (14.5%) relative to collegians in the general population, but
      considerable ever smoking (65.1%) and multiple types of tobacco use (37.3%). The
      authors report on factors associated with tobacco use and on students' exposure
      to cigarette marketing, gaps experienced in receipt of antitobacco messages and
      services, and students' antitobacco intervention recommendations. Limitations of
      the research are described, including possible underreporting of participants'
      tobacco use.

PMID- 17225641
TI  - Collect copays and deductibles up front to reduce bad debt and enhance your
      hospital's margins.

PMID- 17225642
TI  - Fellowship program identifies, trains physician leaders.

PMID- 17225643
TI  - Mentor programs help create leaders of tomorrow.

PMID- 17225644
TI  - The passage to adulthood: challenges of late adolescence.
AB  - Late adolescence and the period following, often referred to as emerging
      adulthood, have been noted as particularly important for setting the stage for
      continued development through the life span as individuals begin to make choices
      and engage in a variety of activities that are influential for the rest of their
      lives. Demographic, sociocultural, and labor market changes have made the years
      between ages eighteen and twenty-five more transitional than in the recent past.
      This chapter reviews the critical assets and needs that are essential for keeping
      youth on healthy, productive pathways into adulthood and examines the
      developmental tasks and changes of late adolescence.

PMID- 17225645
TI  - Designing for diversity: incorporating cultural competence in prevention programs
      for urban youth.
AB  - Low-income urban youth of color frequently confront a wide variety of challenges
      and hardships that other young people never experience. The offering of
      prevention programs represents one strategy to help urban youth avoid the risks
      associated with substance abuse. In this chapter, an alternative program strategy
      is posited-one that places diversity with respect to culture, class, and
      environment at the center of prevention efforts. Such an approach, the authors
      argue, is more effective not only in appealing to the sensibilities of urban
      youth but also in altering their behavior.

PMID- 17225646
TI  - Teens and technology: preparing for the future.
AB  - In the past two decades, economic, technological, demographic, and political
      forces have stimulated major change in the learning and working landscape for
      young people. These circumstances compel us to prioritize the integration of
      technology skill building into youth development experiences in order to better
      prepare older youth for the challenges and responsibilities ahead. Facilitating
      older youth's acquisition of technology skills must continue to be a principal
      goal of policymakers, city leaders, and youth program providers. This chapter
      looks at the integration of technology skill building into youth development
      experiences with consideration of gender and races differences in technology
      access and utilization, along with challenges that at-risk teens face.

PMID- 17225647
TI  - First Things First: a framework for successful secondary school reform.
AB  - If youth development initiatives are going to focus on outcomes that we know are
      important in settings that we know can change these outcomes, the first outcomes
      should be educational, and the first setting should be school. School reform
      presents the most feasible, defensible, and informed opportunity for public
      policy to improve the life chances of children and youth in disadvantaged
      communities. This chapter introduces First Things First (FTF), a school reform
      framework grounded in research about how young people develop and how schools
      promote students' engagement and learning. The chapter explores four critical
      features of FTF that focus on students: (1) continuity of care; (2) increased
      instructional time; (3) high, clear, and fair standards; and (4) enriched
      opportunities for students. The critical features of FTF are implemented through
      three strategies: small learning communities, a family advocate system, and
      instructional improvement.

PMID- 17225648
TI  - Three high school after-school initiatives: lessons learned.
AB  - Alarmed by the large numbers of high school-age youth who are disengaged at
      school and leaving high school without a diploma or the important skills for the
      workplace, policymakers and youth advocates are beginning to see high school
      after-school as the new frontier in after-school programming. Although older
      youth represent a sizable percentage of American students, they garner only a
      small fraction of the federal, state, and local investments for after-school
      programs. This chapter reviews the insights and lessons learned from three after
      school initiatives that have shown success in attracting high school students to
      their programs and engaging them in meaningful activities to support their
      success in school and transition to early adulthood: the After School Safety and
      Education for Teens, After School Matters, and the After-School Corporation.
      Emerging from these pioneering efforts are some promising practices and program
      models that can guide the development of future after-school programs, but not
      without the help of policymakers and funders, both public and private.

PMID- 17225649
TI  - Young people and social action: youth participation in the United Kingdom and
      United States.
AB  - This chapter provides two case studies of projects in the United Kingdom and
      United States using a social action approach to encourage youth participation and
      civic engagement. The authors provide a snapshot of U.K. and U.S. policy related
      to inclusionary practice in youth development work, along with testimony from
      youth participating in the two community development initiatives. As part of the
      positive youth development approach, youth inclusion is seen as a key to policy,
      programs, planning, and practice with young people. Educators, researchers, and
      practitioners using participatory methodologies have continued to move the youth
      development field forward. Social action provides a theory and practice that
      enhances community building, social cohesion, and positive youth development.

PMID- 17225650
TI  - Workforce development for older youth.
AB  - The challenges facing youth who are disconnected from our nation's employment and
      education systems are expansive. Research has suggested that youth services and
      supports that are grounded in a developmental approach not only help young people
      avoid self-destructive behavior, but also enable them to acquire the academic and
      work-readiness skills and personal attributes that employers seek. In 1995, the
      National Youth Employment Coalition and its members established the Promising and
      Effective Practices Network (PEPNet) to identify the key elements of quality
      youth programs and develop tools that would help organizations establish, connect
      to, and promote quality programs. PEPNet represents a standards framework that
      captures the key elements common to successful programs that connect youth to
      jobs, careers, and education. This chapter provides some insights into the
      current practices that have been implemented to facilitate older youth's
      transition to the workforce and highlights the supports youth need for successful
      adulthood, citizenship, and career pursuits.

PMID- 17225651
TI  - Going the distance: serving the needs of older youth at scale.
AB  - Few communities have developed successful strategies for attracting large numbers
      of older youth to their out-of-school-time programs. In addition to meeting the
      unique developmental and programmatic needs of this population, communities have
      struggled with the challenge of creating communitywide integrated approaches to
      service delivery and resource development. Communities wanting to build a system
      of supports for older youth must do so in the context of a communitywide strategy
      as opposed to fragmented, individually operating programs and services. A
      communitywide strategy creates greater opportunity for strategic mobilization of
      resources, greater funding leverage, evaluation and assessment consistency, and
      more powerful input into creating a public voice and public will for supporting
      and serving older youth as they make the transition to adulthood.

PMID- 17225652
TI  - Supporting older youth: what's policy got to do with it?
AB  - The nonschool hours are an underused tool in supporting older youth in their
      transition to adulthood. Given competing demands on many teens' time and a host
      of other developmental realities, effective strategies for engaging high
      schoolers look much different from those of their younger counterparts, and those
      differences have programmatic and policy implications. Effective youth policies
      reflect an overarching vision that is about changing lives--a vision that
      addresses a range of risk and protective factors, simultaneously supports
      discrete programs and builds coherent pathways to success, and recognizes that
      children and youth grow up in families and communities. This chapter highlights
      policy innovations related to teens' involvement in out-of-school-time activities
      and then looks at three principles that can help ensure that youth policy
      supports the full range of older youth's unique developmental, social, and
      economic needs.

PMID- 17225653
TI  - "Tobacco has a purpose, not just a past": Feasibility of developing a culturally
      appropriate smoking cessation program for a pan-tribal native population.
AB  - Tobacco has long held spiritual significance to Native people of North America
      but, because of recreational use, it has become a health risk relatively
      recently. More Native people smoke than any other ethnic group (41 percent vs. 24
      percent in whites and blacks), and death rates caused by tobacco-related diseases
      are disproportionately high. However, no tested, culturally tailored smoking
      cessation programs exist for this group. We used a critical-interpretive
      framework to understand the meaning of tobacco and the feasibility of smoking
      cessation interventions in a pan-tribal population. In June 2004, the University
      of Kansas Medical Center (KUMC) and the Oklahoma Area Indian Health Service (IHS)
      collaborated on six focus groups with (IHS) patients. The patients served
      represent over 200 different nations. Our participants provided us with
      modifications to a currently untested program designed by the Muscogee Nation of
      Oklahoma's Tobacco Prevention Program to enhance cultural appropriateness,
      including (1) an emphasis on visual presentation and a "Native" look to program
      educational materials; (2) comprehensive information about tobacco, quitting, and
      coping among Native people; (3) an acknowledgment and incorporation of
      traditional tobacco use and its diversity; and (4) the use of talking circles and
      counseling with Native facilitators.

PMID- 17225654
TI  - At the back stage of prenatal care: Japanese Ob-Gyns negotiating prenatal
      diagnosis.
AB  - In this article, I explore the reluctance of Japanese ob-gyns to discuss prenatal
      diagnosis (PND) tests with pregnant women. The analysis focuses on the culturally
      specific ways in which ob-gyns formulate their cautiousness and criticism toward
      PND while invoking a local moral economy. Analyzing ob-gyns' accounts, I show how
      the ambiguities of PND are constituted in a specific moment in Japanese culture,
      history, disability politics, and national reproductive policies and are
      formulated through local paradigms of thinking about pregnant women, their
      fetuses, and the process of becoming a person in Japanese society. Finally, I
      show how PND in Japan is pushed to a "back-stage" realm in which the diagnosis
      for fetal anomalies is practiced in secrecy.

PMID- 17225655
TI  - Genetic counseling for sex chromosome anomalies (SCAs) in Israel and Germany:
      assessing medical risks according to the importance of fertility in two cultures.
AB  - In this article, I report findings from a comparative study of Israeli and German
      genetic counselors. Specifically, it concerns counselors' attitudes and risk
      assessments relating to prenatal diagnosis of sex chromosome anomalies (SCAs)
      such as Klinefelter and Turner syndromes. Data collected through in-depth
      interviews with counselors in both countries (N = 32) are presented, and the
      types of claims experts deploy in their personal and professional estimation of
      the risks involved in SCAs are analyzed. The article concludes by suggesting that
      the counselors rhetoric concerning SCAs, whose major manifestation is the future
      infertility of the unborn child as well as their estimations of the related
      risks, should be situated in a broader cultural context, that of local Israeli
      and German understandings of the importance of fertility, and not in their
      professional nondirective ethos. Hence, to understand the practice of genetic
      counselors in two late-modern societies, one must understand the unique
      relationship between the individual bodies of pregnant women and the body
      politics of their nations, a relationship mediated by the counselors, who are the
      bearers of knowledge and expertise in this field.

PMID- 17225656
TI  - Chikotsa--secrets, silence, and hiding: social risk and reproductive
      vulnerability in central Mozambique.
AB  - In this article, I examine pregnancy narratives and patterns of reproductive
      health seeking among women of fertile age in central Mozambique. I map the
      interplay between gendered economic marginalization, maternal risk perceptions,
      and pregnancy management strategies. By interpreting my data in light of Shona
      illness theories, I illuminate the ways that embodied experiences of reproductive
      vulnerability, risk perceptions, and social inequalities are linked: women
      attribute the most serious maternal complications to human- or spirit-induced
      reproductive threats of witchcraft and sorcery. This construction of reproductive
      vulnerability as social threats related to material and social competition
      significantly influences prenatal health seeking. Data reveal the structural and
      cognitive gap between biomedical constructions of risk and lay social threat
      perceptions. Plural health care systems are strategically utilized by women
      seeking to minimize both social and biological harm. On-the-ground ethnography
      shows that maternal health initiatives must take this plurality into full and
      accommodative account to achieve viable improvements in reproductive care and
      outcomes.

PMID- 17225657
TI  - Care for infibulated women giving birth in Norway: an anthropological analysis of
      health workers' management of a medically and culturally unfamiliar issue.
AB  - The focus of this article is on Norwegian health care workers' experience and
      management of birth care of women who have undergone infibulation. Because
      infibulation is the most extensive form of female genital cutting, infibulated
      women experience a higher risk of birth complications, and health workers
      generally experience delivery care for this group as challenging. Infibulated
      women, who come from recently arrived immigrant groups, are a challenge to the
      predominant Norwegian birth philosophy of "natural childbirth" and the positive
      evaluation of everything considered natural. The challenges relate to a mixture
      of technical know-how and a complex set of interpretations of central cultural
      elements of gender, nature, health, and gender equity. The findings suggest that
      a combination of taboo, silence, limited knowledge, and emotional difficulty
      along with a wish to be culture sensitive may at times prove counterproductive to
      giving the best help. Health care workers often seem to impose "imagined"
      cultural values on infibulated women, rather than clarifying them through
      personal communication.

PMID- 17225658
TI  - Childhood sexual abuse and HIV risk among crack-using commercial sex workers in
      San Salvador, El Salvador: a qualitative analysis.
AB  - This article explores the relationship between childhood sexual abuse (CSA) and
      later HIV risk. It draws on qualitative, in-depth interviews with 40 women who
      either used crack or engaged in commercial sex work in the greater metropolitan
      area of San Salvador, El Salvador, 28 of whom experienced CSA. Although the
      relationship between CSA and later HIV risk has been clearly demonstrated, the
      processes that lead women who have experienced CSA to experience HIV risk are
      unclear. The theoretical model presented here incorporates the psychological
      effects of CSA, particularly stigmatization, as well as its social consequences
      and the larger context of poverty in which these women live. The meanings women
      draw from past abuse experiences and their rationale for choices made help
      explain the association between CSA and later risk as mediated through sex work
      and crack addiction. Self-report data gathered in this study indicate that HIV
      prevalence may be considerably higher in this high-risk population than
      Salvadoran national rates.

PMID- 17225659
TI  - The roles of sex, gender, and coping in adolescent depression.
AB  - This study investigated the roles of coping and masculinity in higher rates of
      depressive symptoms among adolescent girls, as compared to boys. A model was
      designed and tested through path analysis, which involved the variables of sex,
      gender, problem-focused coping, rumination, and distraction. The Reynolds
      Adolescent Depression Scale and the Bem Sex Role Inventory, as well as a measure
      of coping with general stressors was completed by 246 adolescents. Results showed
      that adolescent girls were more depressed than boys, and that girls used more
      emotion-focused and ruminative coping than did boys. Greater degrees of
      ruminative coping were related to high levels of depressive symptoms. Problem
      focused and distractive coping were positively correlated with masculinity and
      negatively associated with depression. Surprisingly, girls were more likely to
      use problem-focused coping. Problem-focused and distractive coping were found to
      mediate the negative relationship between masculinity and depression.

PMID- 17225660
TI  - Adolescents' psychological response to the experience of community interpersonal
      violence: a cross-national and a cross-cultural comparison.
AB  - A comparative cross-national study investigating the level of experience with
      community interpersonal violence, level of psychological distress, and the
      relationship between exposure and distress among adolescents is presented.
      Participants were 617 first-year college students comprising African Americans
      and Jamaican Americans living in New York City, and Jamaicans living in Kingston,
      Jamaica. The three groups are similar in terms of age, gender, educational level,
      and race; they differ in location of residence, culture, and immigration status.
      Location of residence is related to exposure; immigration status is related to
      distress; but culture is not related to vulnerability when exposed. The effect
      size of the relationship between exposure and distress appears to be robust
      across variations in culture, amount of exposure, and level of distress.

PMID- 17225661
TI  - Risk factors for depression in early adolescence.
AB  - The purpose of this study was to identify salient risk factors for depression in
      early adolescence from a group of common predictors. The following nine
      predictors were examined: (1) perceived quality of peer relationships, (2)
      perceived parental nurturance, (3) perceived parental rejection, (4) self-esteem,
      (5) body image, (6) pubertal status, (7) SES, (8) conduct problems, and (9)
      hyperactivity/inattention. The sample of 2,014 12 and 13 year olds was also
      divided by gender to examine potential sex differences in risk factors for
      depression. Finally, several mediational models were investigated. Self-esteem
      emerged as the strongest predictor of depression in both genders; parental
      behavior also emerged as an important risk factor. Therefore, these two variables
      are discussed as targets for those developing intervention and prevention
      programs.

PMID- 17225662
TI  - Bullying and victimization among black and Hispanic adolescents.
AB  - The prevalence of bullying and victimization by gender, grade level, and
      race/ethnicity was examined among a sample of low socioeconomic, Black and
      Hispanic 6th- to 12th-graders in a large urban school district in Texas. Bullying
      and victimization were measured using specific behaviors. Students were
      classified as bullies (7%), victims (12%), bully-victims (5%), or neither (76%),
      depending on the number and frequency of reported experiences. For specific types
      of bullying (e.g., spreading rumors, excluding others), 4.5%-9.4% of students
      reported participation. Specific types of victimization (e.g., being hit or
      pushed, picked on) ranged from 6%-12%. Gender differences were not observed for
      general bullying and victimization, but physical and some verbal types were more
      prevalent among males. Blacks were more likely to participate in bullying and
      victimization, and these experiences seemed to peak in the 9th grade. This study
      adds to the literature as few U.S. studies on both general and specific types of
      bullying have been conducted among low socioeconomic, racial/ethnic minority
      students in middle and high school.

PMID- 17225663
TI  - Racial discrimination-induced anger and alcohol use among black adolescents.
AB  - This study explored whether a relationship exists between anger among Black
      adolescents that has been provoked by racial discrimination, and alcohol
      consumption. Participants consisted of 134 Black adolescents from 14 to 18 years
      of age, residing in northeast Texas. All participants were administered a
      questionnaire measuring whether and the extent to which they might be dependent
      upon alcohol, a background information questionnaire which included questions
      about their drinking pattern, and a measure designed to assess the extent to
      which they feel angry either because they had been discriminated against or
      observed other Blacks being discriminated against or observed other Blacks being
      discriminated against in various situations. Only gender was found to be
      predictive of scores on the dependency scale. However gender, age, and racial
      discrimination anger scores were found to be predictive of the amount of alcohol
      consumed by the participants. Some implications for theory, research, and
      intervention are suggested.

PMID- 17225664
TI  - The success of Taiwanese fathers in guiding adolescents.
AB  - The purpose of this study was to examine similarities and differences in
      Taiwanese fathers' and adolescents' perceptions of paternal competencies. A multi
      source (fathers (n = 176) and 10- 14-year-old adolescent children (n = 176),
      single-method (both generations completed the Parent Success Indicator)
      investigation was employed. Generational assessments were compared, and effects
      of independent variables were examined. Impressions from both generations were
      significantly different by child school grades and the amount of time fathers
      spent talking to and doing things with their adolescents.

PMID- 17225665
TI  - Future time perspective and motivational categories in Argentinean adolescents.
AB  - This study is based on a sample of 332 Argentinean teenagers in their last year
      of secondary school. In the context of the relational theory of motivation, an
      attempt is made to determine the motivational categories best predicting Future
      Time Perspective (FTP) extension. The influence of the sex, locus of control,
      social class, and school ethos variables on FTP extension is also explored. A
      scale measuring locus of control and the Motivational Induction Method (MIM) have
      been employed to obtain the data. Through stepwise multiple regression, a
      predictive set is determined, made up of life-meaning values, self-fulfillment,
      academic achievement motivation, locus of control, sensual values, and social
      contact. Significant differences are found in FTP extension and locus of control
      in relation to school ethos. The Mann-Whitney and Kruskal-Wallis tests are used
      as statistical proof. A one-way ANOVA is run to examine the relationship between
      locus of control and school ethos levels. The possibility of a motivational
      profile common to Argentinean teenagers is considered and the pedagogical
      consequences of the findings are discussed.

PMID- 17225666
TI  - The influence of dispositional optimism and gender on adolescents' perception of
      academic stress.
AB  - This study investigated the role of optimism together with gender, on students'
      perception of academic stress. Four hundred and thirty secondary school students
      from Singapore participated in this study and data were collected using two self
      report measures: the Life Orientation Test and the Academic Expectation Stress
      Inventory. Results revealed a significant negative relationship between optimism
      and academic stress in students. Gender was not a significant predictor of
      academic stress and no two-way interactions were found between optimism and
      gender of the participants. Possible explanations for the results were suggested
      and implications of the findings were discussed.

PMID- 17225667
TI  - Adolescents' sexual self-disclosure on the internet: deindividuation and
      impression management.
AB  - This study examined the effect of anonymity on adolescents' sexual self
      disclosure on the Internet and the impact of topic intimacy on their reply intent
      for sexual disclosure by conducting a survey with 1,347 adolescents. It was found
      that male participants were more likely than females to engage in sexual self
      disclosure and to correspondingly respond to cyber partners' sexual disclosure.
      Results showed that the greater the anonymity, the greater the intent for sexual
      self-disclosure. Participants exhibited greater reply intent when cyber partners
      self-disclosed sexual topics with greater intimacy, and the effect of topic
      intimacy was more pronounced in male participants. The findings suggest that male
      adolescents tend to adopt a reciprocal strategy in responding to partners' sexual
      disclosure on the Internet, whereas females tend to employ a conservative
      strategy. It was concluded that male and female adolescents revealed differential
      self-presentation and impression management for their sexual self-disclosing and
      responding on the Internet.

PMID- 17225668
TI  - Perceived parent-child relational qualities and parental behavioral and
      psychological control in Chinese adolescents in Hong Kong.
AB  - Chinese secondary school students (N = 3,017) were asked to respond to
      instruments measuring their perceived parent-child relational qualities (parental
      trust of the child, child's trust of parents, child's readiness to communicate
      with parents, and child's satisfaction with parental control), parental
      behavioral control (including indicators of knowledge, expectation, monitoring,
      discipline, and demandingness), and parental psychological control. Results
      showed that parental trust of the child and child's trust of parents were
      positively related to child's readiness to communicate with the parents and
      satisfaction with parental control. While parental trust of the child and child's
      trust of parents were basically negatively related to different aspects of
      behavioral control (except parental knowledge), readiness to communicate with the
      parents and satisfaction with parental control were positively associated with
      parental control. Parent-child relational quality measures were negatively
      related to psychological control. Relative to measures of parental behavioral
      control, parental psychological control was a stronger predictor of parent-child
      relational qualities. The present findings clarify the parent-child relational
      quality correlates of parental behavioral and psychological control.

PMID- 17225669
TI  - Rhythmic characteristics of colloquial and formal Tamil.
AB  - Application of recently developed rhythmic measures to passages of read speech in
      colloquial and formal Tamil revealed some significant differences between the two
      varieties, which are in diglossic distribution. Both were also distinguished from
      a set of control data from British English speakers reading an equivalent
      passage. The findings have implications for the usefulness of the rhythmic
      measures and also the temporal characteristics of Tamil. High levels of
      interspeaker variability affected the measures; in some cases differences within
      each group of five speakers exceeded those separating distinct languages,
      indicating that such measures may not be reliable indicators of typological
      status. Discrepancies between previous findings and remeasurements of the same
      data also show the measures to be sensitive to differences in measurement
      criteria, specifically the treatment of pauses. The results confirm that the
      differences between colloquial and formal Tamil encompass durational
      characteristics, which appear to be largely explicable from differences in their
      syllabic structure. Provisional comparison with other languages suggests that
      their rhythmic properties cannot easily be captured by reference to traditional
      rhythmic classes. This may explain previous confusion in the literature over
      Tamil's temporal characteristics, which have been variously described in terms of
      stress-timing, syllable-timing, and mora-timing.

PMID- 17225670
TI  - Spontaneous speech events in two speech databases of human-computer and human
      human dialogs in Spanish.
AB  - Previous works in English have revealed that disfluencies follow regular patterns
      and that incorporating them into the language model of a speech recognizer leads
      to lower perplexities and sometimes to a better performance. Although work on
      disfluency modeling has been applied outside the English community (e.g., in
      Japanese), as far as we know there is no specific work dealing with disfluencies
      in Spanish. In this paper, we follow a data driven approach in exploring the
      potential benefit of modeling disfluencies in a speech recognizer in Spanish. Two
      databases of human-computer and human-human dialogs are considered, which allow
      the absolute and relative frequencies of disfluencies in the two situations to be
      compared. The rate of disfluencies in human-human dialogs is found to be very
      close to that found for similar databases in English. Due to setup factors, the
      rate of disfluencies found in human-computer dialogs was remarkably higher than
      that reported for similar databases in English. In any case, from the point of
      view of speech recognition, the high frequencies of disfluencies and the distinct
      features of the acoustic events related to them support the need for explicit
      acoustic models. The regularities observed in the distribution of filled pauses
      and speech repairs reveal that including them in the language model of the speech
      recognizer may be also helpful. The extent to which the number of events depends
      on utterance length and on the speaker is also explored. Statistics are shown
      that follow previous studies for English, and a sizeable space is devoted to
      comparing our results with them. Finally, various possible cues for the automatic
      detection of speech repairs--a key issue from the point of view of speech
      understanding--are explored: silent pauses, filled pauses, lengthenings, cut off
      words and discourse markers. As previously observed for English, none of them was
      found to be reliable by itself. More information, especially at the acoustic
      prosodic level, is no doubt needed to reliably detect speech repairs.

PMID- 17225671
TI  - Finding referents in time: eye-tracking evidence for the role of contrastive
      accents.
AB  - In two eye-tracking experiments the role of contrastive pitch accents during the
      on-line determination of referents was examined. In both experiments, German
      listeners looked earlier at the picture of a referent belonging to a contrast
      pair (red scissors, given purple scissors) when instructions to click on it
      carried a contrastive accent on the color adjective (L + H*) than when the
      adjective was not accented. In addition to this prosodic facilitation, a general
      preference to interpret adjectives contrastively was found in Experiment 1: Along
      with the contrast pair, a noncontrastive referent was displayed (red vase) and
      listeners looked more often at the contrastive referent than at the
      noncontrastive referent even when the adjective was not focused. Experiment 2
      differed from Experiment 1 in that the first member of the contrast pair (purple
      scissors) was introduced with a contrastive accent, thereby strengthening the
      salience of the contrast. In Experiment 2, listeners no longer preferred a
      contrastive interpretation of adjectives when the accent in a subsequent
      instruction was not contrastive. In sum, the results support both an early role
      for prosody in reference determination and an interpretation of contrastive focus
      that is dependent on preceding prosodic context.

PMID- 17225672
TI  - Within- word prosodic constraint on coarticulation in Japanese.
AB  - The present study addresses the question of how within-word prosodic constituent
      boundaries constrain V-to-V coarticulation in Japanese. The smallest prosodic
      unit that might affect V-to-V coarticulation is the bimoraic foot. The effect of
      the foot boundary is observed in the present study: the bimoraic foot constrains
      the extent of V-to-V coarticulation in both left-to-right and right-to-left
      directions. For the target vowel /a/, anticipatory V-to-V effects are stronger
      than carryover effects for both within-foot and across-foot conditions. Also, the
      foot constraint works more strongly on anticipatory than on carryover effects.
      Some idiosyncratic variation is observed across speakers; however, even some
      deviant behavior can partly be explained as the result of the interaction of C-to
      V and V-to-V effects and speech rate. Coarticulation is observed to be the
      product of a complex process of constraint interaction.

PMID- 17225673
TI  - Never too safe.

PMID- 17225674
TI  - DNA bar code: screening methods of colorectal cancer.

PMID- 17225675
TI  - Investigating elevated potassium values.

PMID- 17225676
TI  - Lab evaluation of chemical and biological terrorism.

PMID- 17225677
TI  - A healthy transfusion of service from Wyndgate and Dr. Ruxin.

PMID- 17225678
TI  - Dos and don'ts of cross-training.

PMID- 17225679
TI  - What constitutes "accommodating" a disabled employee?

PMID- 17225680
TI  - What HR 686 means to American patients.

PMID- 17225681
TI  - Listen to your heart ... maybe you'll use an FSA.

PMID- 17225682
TI  - Alzheimer's today.

PMID- 17225683
TI  - In cold blood.

PMID- 17225684
TI  - AIDS: we're not there yet.

PMID- 17225685
TI  - [Trends in urology: homage to Professor Hans-Jurg Leisinger].

PMID- 17225686
TI  - [Bladder cancer: understanding the disease and future implications for assessment
      and therapy].
AB  - Since 1940, the evolution in analysis and treatment of bladder cancer refines our
      staging systems and enhances our capabilities in assessing a diagnosis, a
      prognosis and in defining appropriate treatments. Such a study implies a critical
      conceptualisation of tumour developmental pathways, added by the recent
      observations in molecular biology research.

PMID- 17225687
TI  - [Acute and chronic prostatitis, how will we manage it ten years from now?].
AB  - Pelvic pain syndrom arises in an increasing number of men during their life. The
      present classification of prostatitis in four categories facilitates a
      comprehensive review of its diagnosis and treatment. The development of
      techniques related to molecular biology will favour a deeper knowledge in the
      future.

PMID- 17225688
TI  - [Short history of erectile dysfunction treatment].
AB  - Since the origin, the man tried by all possible means to restor his erectile
      capacity. The obscurantism prevailed for a long time. We had to wait up to the
      turn of the 19th Century with Freud to get that things evolve a little bit. In
      the Fifties, the first penile prostheses were developed by Goodwin and Scott. In
      the Sixties, the behavioral therapies by Masters and Johnson. The Eighties
      represent the pharmacological revolution with the discovery of the effects of
      papaverin by Virag, then the E1 prostaglandin by Ishii, as well as the inhibitors
      of the 5 phospho di esterase (sildenafil, vardenafil, tadalafil) following
      studies on nitric oxide by Ignarro, Nobel Prize of medicine in 1998.

PMID- 17225689
TI  - [Urinary lithiasis: history and ethics].
AB  - This paper surveys the evolution of urinary stone treatment, primarily in the
      bladder, from ancient times to the 19th century, taking into consideration, not
      only technical breakthroughs, but also the moral sense of therapists, the social,
      political and religious context of the studied periods, the appreciation of
      symptoms and pain meaning by doctors or barber-surgeons; finally, a set of
      factors which contributes to the evolution of the medical thought.

PMID- 17225690
TI  - [The more it changes, the more it remains the same?].
AB  - Pr H.-J. Leisinger's farewell lesson treats of the evolution of medicine in
      general and urology in particular, in a health system submitted to a global
      change, while emphasizing on the fundamental values of the medical doctor.

PMID- 17225691
TI  - [Hodgkin's disease in children: maximizing survival while minimizing recurrence].

PMID- 17225692
TI  - [The happiness pill...why not?].

PMID- 17225693
TI  - [Taxes, lies, and ideas. When the revision of the value added tax promises a cost
      of health raise of 5.5%].

PMID- 17225694
TI  - [Practical problems of the ECG in the elderly: ventricular bigeminal rhythm. Case
      No, 5].

PMID- 17225695
TI  - [Washington's state of panic: 200 million dollars].

PMID- 17225696
TI  - [Looking at genetics in general and racism in particular].

PMID- 17225697
TI  - [Gamete donation: the right to know genetic origins].

PMID- 17225698
TI  - [A Swedish researcher receives the Schellenberg prize for paraplegia research].

PMID- 17225699
TI  - [EBM, fascism and religion].

PMID- 17225700
TI  - HPV vaccine: a cornerstone of female health.

PMID- 17225701
TI  - Treatment of patients with irritable bowel syndrome.

PMID- 17225702
TI  - Early invasive therapy or conservative management for unstable angina or NSTEMI?

PMID- 17225703
TI  - Hepatitis B vaccine for infants of HBsAg-positive mothers.

PMID- 17225704
TI  - Humidified air for croup?

PMID- 17225705
TI  - Lung cancer: diagnosis and management.
AB  - Lung cancer is the leading cause of cancer-related death in the United States,
      with an average five-year survival rate of 15 percent. Smoking remains the
      predominant risk factor for lung cancer. Lung cancers are categorized as small
      cell carcinoma or non-small cell carcinoma (e.g., adenocarcinoma, squamous cell
      carcinoma, large cell carcinoma). These categories are used for treatment
      decisions and determining prognosis. Signs and symptoms may vary depending on
      tumor type and extent of metastases. The diagnostic evaluation of patients with
      suspected lung cancer includes tissue diagnosis; a complete staging work-up,
      including evaluation of metastases; and a functional patient evaluation.
      Histologic diagnosis may be obtained with sputum cytology, thoracentesis,
      accessible lymph node biopsy, bronchoscopy, transthoracic needle aspiration,
      video-assisted thoracoscopy, or thoracotomy. Initial evaluation for metastatic
      disease relies on patient history and physical examination, laboratory tests,
      chest computed tomography, positron emission tomography, and tissue confirmation
      of mediastinal involvement. Further evaluation for metastases depends on the
      clinical presentation. Treatment and prognosis are closely tied to the type and
      stage of the tumor identified. For stages I through IIIA non-small cell
      carcinoma, surgical resection is preferred. Advanced non-small cell carcinoma is
      treated with a multimodality approach that may include radiotherapy,
      chemotherapy, and palliative care. Chemotherapy (combined with radiotherapy for
      limited disease) is the mainstay of treatment for small cell carcinoma. No major
      organization recommends screening for early detection of lung cancer, although
      screening has interested researchers and physicians. Smoking cessation remains
      the critical component of preventive primary care.

PMID- 17225706
TI  - Leukotriene inhibitors in the treatment of allergy and asthma.
AB  - Leukotriene inhibitors are the first new class of medications for the treatment
      of persistent asthma that have been approved by the U.S. Food and Drug
      Administration in more than two decades. They also have been approved for the
      treatment of allergic rhinitis. Prescriptions of leukotriene inhibitors have
      outpaced the evidence supporting their use, perhaps because of perceived ease of
      use compared with other asthma medications. In the treatment of persistent
      asthma, randomized controlled trials have shown leukotriene inhibitors to be more
      effective than placebo but less effective than inhaled corticosteroids. The use
      of leukotriene inhibitors has not consistently shown an inhaled-steroid-sparing
      effect, a reduction in need for systemic steroid treatment, or a cost savings.
      For exercise-induced asthma, leukotriene inhibitors are as effective as long
      acting beta2-agonist bronchodilators and are superior to placebo; they have not
      been compared with short-acting bronchodilators. Leukotriene inhibitors are as
      effective as antihistamines but are less effective than intranasal steroids for
      the treatment of allergic rhinitis. The use of leukotriene inhibitors in treating
      atopic dermatitis, aspirin-intolerant asthma, and chronic idiopathic urticaria
      appears promising but has not been studied thoroughly. Leukotriene inhibitors
      have minimal side effects and are well tolerated in most populations.

PMID- 17225707
TI  - Childhood and adolescent depression.
AB  - Major depression affects 3 to 5 percent of children and adolescents. Depression
      negatively impacts growth and development, school performance, and peer or family
      relationships and may lead to suicide. Biomedical and psychosocial risk factors
      include a family history of depression, female sex, childhood abuse or neglect,
      stressful life events, and chronic illness. Diagnostic criteria for depression in
      children and adolescents are essentially the same as those for adults; however,
      symptom expression may vary with developmental stage, and some children and
      adolescents may have difficulty identifying and describing internal mood states.
      Safe and effective treatment requires accurate diagnosis, suicide risk
      assessment, and use of evidence-based therapies. Current literature supports use
      of cognitive behavior therapy for mild to moderate childhood depression. If
      cognitive behavior therapy is unavailable, an antidepressant may be considered.
      Antidepressants, preferably in conjunction with cognitive behavior therapy, may
      be considered for severe depression. Tricyclic antidepressants generally are
      ineffective and may have serious adverse effects. Evidence for the effectiveness
      of selective serotonin reuptake inhibitors is limited. Fluoxetine is approved for
      the treatment of depression in children eight to 17 years of age. All
      antidepressants have a black box warning because of the risk of suicidal
      behavior. If an antidepressant is warranted, the risk/benefit ratio should be
      evaluated, the parent or guardian should be educated about the risks, and the
      patient should be monitored closely (i.e., weekly for the first month and every
      other week during the second month) for treatment-emergent suicidality. Before an
      antidepressant is initiated, a safety plan should be in place. This includes an
      agreement with the patient and the family that the patient will be kept safe and
      will contact a responsible adult if suicidal urges are too strong, and assurance
      of the availability of the treating physician or proxy 24 hours a day to manage
      emergencies.

PMID- 17225708
TI  - Informatiom from your family doctor. Depression in children and teens.

PMID- 17225709
TI  - Vascular surgery: an update.
AB  - Caring for patients with vascular illnesses has become increasingly more complex
      and has changed dramatically over the past 10 years, with a widening array of
      diagnostic and treatment options. Carotid artery stenting has the potential to
      become a viable alternative to open surgery in high-risk patients with carotid
      artery disease (i.e., patients older than 80 years and those with previous neck
      surgery or irradiation, contralateral carotid artery occlusion, contralateral
      laryngeal nerve injury, or angina). However, the effectiveness of carotid artery
      stenting as a therapy is still being evaluated in randomized trials. Endovascular
      aortic aneurysm repair is an option for patients who desire or require a less
      invasive modality and who have suitable aortic anatomy. Surgical reconstruction
      remains the standard treatment for ischemic rest pain and tissue loss (critical
      limb ischemia). Balloon angioplasty and stenting are treatment options for
      peripheral vascular disease, although treatment is dependent on the arterial
      segment or segments involved.

PMID- 17225710
TI  - Clinical inquiries: Treatment of acute sciatica.

PMID- 17225711
TI  - Dyspnea and dry cough in a patient with rheumatoid arthritis.

PMID- 17225712
TI  - Pregnant physicians and infectious disease risk.

PMID- 17225713
TI  - Gambel oak.

PMID- 17225714
TI  - Pulmonary complications of common variable immunodeficiency.
AB  - OBJECTIVES: To review pulmonary complications of common variable immunodeficiency
      (CVID) and summarize data available on the use of replacement antibody treatment
      to protect against lung changes. DATA SOURCES: Relevant articles regarding CVID
      and pulmonary disease identified from PubMed and reference lists of review
      articles. STUDY SELECTION: Key articles were selected by the authors. RESULTS:
      Patients with CVID often develop acute sinopulmonary infections that can lead to
      chronic airway inflammation, which can produce substantial morbidity and
      mortality. Replacement immunoglobulin treatment significantly reduces the
      reoccurrence of lower airway infections, but the effect on the development of
      chronic lung damage is not yet clear. Screening examinations, such as pulmonary
      function testing and high-resolution computed tomography of the chest, can be
      used to evaluate pulmonary status. Patients with abnormal findings may benefit
      from more aggressive treatment, including larger doses of immune globulin and the
      use of prophylactic antibiotics. CONCLUSIONS: Pulmonary complications present a
      significant comorbidity in CVID; monitoring may indicate which patients require
      more aggressive treatment.

PMID- 17225715
TI  - Formulation considerations of intranasal corticosteroids for the treatment of
      allergic rhinitis.
AB  - OBJECTIVE: To examine how various aspects of an intranasal corticosteroid (INS)
      formulation may influence the efficacy, tolerability, and patient preference and
      adherence to INS therapy. DATA SOURCES: A PubMed search of the literature was
      conducted for studies on allergic rhinitis published between January 1977 and
      January 2006 using the keywords intranasal corticosteroid, preservatives,
      benzalkonium chloride, and tonicity. STUDY SELECTION: Prospective studies,
      retrospective studies, and case reports were selected for inclusion in this
      review. RESULTS: Currently available INSs are effective first-line treatments for
      allergic rhinitis. Differences in patient preference for a particular INS are
      largely attributable to sensory attributes of the nasal spray, which arise from
      characteristics of the formulation. Additives and preservatives can cause
      tolerability issues by irritating the mucosal membranes and causing nasal drying,
      or they can confer an unpleasant odor or taste to an INS formulation. The
      relative osmotic pressure, or tonicity, of an INS can modulate nasal absorption
      and retention, thereby potentially influencing the clinical efficacy.
      Characteristics such as delivery device and spray volume can affect a patient's
      perception and experience with a particular INS. Newer INSs, such as ciclesonide,
      are in development for the treatment of allergic rhinitis, and consideration of
      the formulation characteristics of these agents is an important part of the
      development process. CONCLUSIONS: INSs are an effective treatment option for
      patients with allergic rhinitis; however, there is room for formulation
      improvement. Optimization of formulation may increase the efficacy, tolerability,
      and patient preference and adherence to INSs.

PMID- 17225716
TI  - Induction of airway remodeling of nasal mucosa by repetitive allergen challenge
      in a murine model of allergic rhinitis.
AB  - BACKGROUND: Although many studies regarding airway remodeling in asthma have been
      reported, only a few studies have investigated airway remodeling in allergic
      rhinitis. OBJECTIVES: To determine whether repetitive allergen challenge could
      induce airway remodeling in the nose and evaluate the effect of steroids using a
      murine model of allergic rhinitis. METHODS: To develop a mouse model of airway
      remodeling, ovalbumin-sensitized mice were repeatedly exposed to inhaled
      ovalbumin administration twice a week for 1 month and 3 months. Matched control
      mice were challenged with phosphate-buffered saline, and the treatment group
      received intraperitoneal dexamethasone injection. Trichrome, periodic acid
      Schiff, hematoxylin-eosin, and immunohistochemical staining against matrix
      metalloproteinase 9 and tissue inhibitors of metalloproteinase 1 were performed
      to nasal and lung tissues, and the level of transforming growth factor beta in
      the nasal lavage fluid was analyzed. RESULTS: Repetitive ovalbumin challenge for
      3 months induced circumferential peribronchial fibrosis in the lung. In the nose,
      subepithelial fibrosis, increased matrix metalloproteinase 9 and tissue
      inhibitors of metalloproteinase 1 expression, goblet cell hyperplasia, and
      submucous gland hypertrophy were observed compared with the control group.
      Features of airway remodeling were more prominent in the lung tissue.
      Administration of dexamethasone significantly inhibited these histologic changes.
      CONCLUSION: Airway remodeling associated with long-term allergen challenge can
      occur in the nasal mucosa and the lung. Steroid treatment prevents airway
      inflammation in response to acute allergen challenge, as well as airway
      remodeling by long-term allergen challenge.

PMID- 17225717
TI  - Radiographic resolution of chronic rhinosinusitis without polyposis after 6 weeks
      vs 3 weeks of oral antibiotics.
AB  - BACKGROUND: Maximal medical therapy is poorly defined in chronic sinusitis
      treatment. OBJECTIVE: To objectively evaluate the radiographic response of
      chronic rhinosinusitis without polyposis after 3 and 6 weeks of oral antibiotics.
      METHODS: Thirty-five patients with confirmed chronic sinusitis without polyposis
      (disease apparent on initial computed tomography [CT] with appropriate symptom
      duration) were prescribed 6 weeks of antibiotics. When possible, culture-directed
      antibiotics were used; otherwise clindamycin was used empirically. A CT was
      performed after 3 and 6 weeks of therapy. CTs were then graded by the Lund-Mackay
      system. Demographic data were reviewed. RESULTS: Of the 35 patients, 16 underwent
      all 3 CT scans and completed all 6 weeks of antibiotics. Three patients completed
      only 3 weeks of antibiotics, and 16 did not undergo the interval 3-week CT. Six
      patients (38%) had statistically significant improvement in their CT scans
      between weeks 3 and 6. In this subset of patients who improved, 37% of their
      overall radiographic improvement occurred in the 3- to 6-week treatment interval.
      No prognostic variables predicted which patients would radiographically improve
      after 3 weeks of antibiotics. CONCLUSION: Some patients achieve radiographic
      improvement and disease resolution after the completion of a 3-week course of
      antibiotics. Therefore, maximal medical therapy for chronic sinusitis may consist
      of longer than 3 weeks of therapy to ensure maximal benefit.

PMID- 17225718
TI  - Asthma hospitalizations among US military personnel, 1994 to 2004.
AB  - BACKGROUND: Acute asthma attacks strike unpredictably and may lead to
      hospitalization in otherwise healthy individuals. The burden of asthma
      hospitalization on the US health care system has greatly interested health care
      workers, many of whom see the incidence of asthma as increasing. OBJECTIVES: To
      examine the annual incidence of hospitalization and the frequency of subsequent
      hospitalization for asthma among all active-duty US military personnel between
      1994 and 2004 and to determine demographic and occupational risk factors of
      asthma hospitalization within this generally healthy US population. METHODS:
      Annual demographic and occupational data were combined with electronic
      hospitalization records for patients with a discharge diagnosis of asthma. Using
      Cox proportional hazard modeling, the authors investigated demographic and
      occupational risk factors for asthma hospitalization. RESULTS: Women, married
      persons, health care workers, enlisted personnel, US Army personnel, and older
      persons were found to have a significantly greater risk of asthma
      hospitalization. Yearly rates of hospitalization declined from 22.3 per 100,000
      persons to 12.6 per 100,000 persons between 1994 and 2004. CONCLUSIONS: Although
      these data have some limitations, they suggest that the burden of asthma
      hospitalizations in the large, healthy population of US military personnel has
      declined during the last decade. The decrease in hospitalization potentially
      reflects improved outpatient management strategies.

PMID- 17225719
TI  - Association of airway hyperresponsiveness with reduced quality of life in
      patients with moderate to severe asthma.
AB  - BACKGROUND: Airway hyperresponsiveness (AHR) is an indicator of poor asthma
      control. Asthma patients with AHR to methacholine have been shown to have a
      poorer quality of life compared with asthma patients without AHR, but it is not
      clear to what degree this is a result of more severe disease in patients with
      AHR. OBJECTIVES: To describe the relationship between AHR and quality of life in
      asthma patients and to determine the impact of the severity of asthma on this
      relationship. METHODS: Data from 691 asthma patients were analyzed to describe
      the relationship between the impact of AHR to methacholine (cumulative dose of
      methacholine required to provoke a 20% decrease in forced expiratory volume in 1
      second, < or = 8 micromol) on quality of life (measured by the Asthma Quality of
      Life Questionnaire) of asthma patients in relation to the severity of asthma
      (according to the Global Initiative for Asthma guidelines). RESULTS: Asthma
      patients with AHR had more severe asthma and a poorer quality of life compared
      with asthma patients without AHR. Furthermore, the quality of life decreased with
      increasing severity of asthma. However, regression analysis showed an independent
      association between both the presence of AHR and the severity of asthma and
      quality of life, as well as an interaction between the effects of these 2
      factors. Finally, subgroup analysis showed that the impact of AHR on the quality
      of life was only clinically significant in moderate to severe asthma but not in
      mild asthma. CONCLUSIONS: AHR is associated with a negative impact on the quality
      of life of asthma patients that is partly independent of the severity of asthma.

PMID- 17225720
TI  - Staphylococcus colonization in atopic dermatitis treated with fluticasone or
      tacrolimus with or without antibiotics.
AB  - BACKGROUND: The skin of patients with atopic dermatitis (AD) exhibits a striking
      susceptibility to colonization and infection by Staphylococcus aureus. Treatment
      with topical anti-inflammatory drugs alone can reduce S. aureus colonization.
      OBJECTIVES: To compare the clinical severity of AD and the S. aureus colonization
      rate between AD patients treated with topical glucocorticoids and those treated
      with tacrolimus and to evaluate the effects of complementary topical
      antistaphylococcal antibiotic therapy and the development of fusidic acid
      resistant S. aureus. METHODS: Sixty AD patients were enrolled in a prospective,
      parallel, randomized study of an 8-week treatment with topical 0.05% fluticasone
      propionate or 0.03% tacrolimus, with or without complementary fusidic acid.
      Disease severity scoring of AD based on SCORing of Atopic Dermatitis (SCORAD),
      colonization rate and density of S. aureus on the skin, and antibiotic
      susceptibility of S. aureus isolates were evaluated. RESULTS: The reduction in
      SCORAD scores correlated with the reduction of S. aureus numbers. Treatment with
      topical tacrolimus resulted in a comparable reduction in SCORAD scores to
      fluticasone but a slower eradication of S. aureus. Complementary fusidic acid had
      no additional benefit compared with fluticasone or tacrolimus alone. Two patients
      developed fusidic acid-resistant S. aureus after 8 weeks of fusidic acid
      treatment. CONCLUSION: Tacrolimus is an appropriate alternative treatment for
      chronic AD. Topical anti-inflammatory therapy alone to improve the allergic skin
      inflammation of AD can reduce S. aureus colonization of the skin. Topical
      antibiotics should be reserved for short-term use in obvious secondary bacterial
      infection.

PMID- 17225721
TI  - Investigation of angioedema associated with the use of angiotensin-converting
      enzyme inhibitors and angiotensin receptor blockers.
AB  - BACKGROUND: Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin
      receptor blockers (ARBs) are known to cause angioedema. OBJECTIVE: To evaluate
      the time to onset of angioedema and the subsequent episodes of angioedema in
      patients initially experiencing ACE-I- or ARB-induced angioedema. METHODS: A
      manual medical record review was conducted on 64 patients with a diagnosis of
      urticaria, angioedema, or anaphylaxis as a result of taking an ACE-I or ARB. Data
      recorded included demographic characteristics; time to onset of symptoms;
      concomitant medication use; laboratory test results; recurrent episodes of
      angioedema, urticaria, or anaphylaxis; and morbidity and mortality. RESULTS: The
      mean age of patients with angioedema was 60.2 years (age range, 32-92 years).
      Women (60%) and African Americans (69%) were affected more commonly. The primary
      location for angioedema was the lips and tongue. Sixty-one of 64 patients
      developed at least one episode of angioedema as the result of taking an ACE-I,
      and 3 patients had angioedema associated with an ARB. The mean time to onset of
      angioedema after initiation of therapy in 51 patients was 1.8 years, with 13
      patients (25%) presenting within the first month and 6 patients (12%) developing
      angioedema in the first week. No patients required a tracheostomy or died. Also,
      none of the 6 patients, whose angioedema was attributed to an ACE-I who then
      received an ARB, developed recurrent angioedema in more than 8.1 patient-years of
      follow-up. CONCLUSIONS: Angioedema attributable to an ACE-I or ARB resolves on
      discontinued use of the medication. It most commonly affects women and African
      Americans and did so in the first month of treatment in 25% of patients.
      Physicians should be aware but not deterred necessarily from recommending an ARB
      in patients with ACE-I-induced angioedema because of the benefits of control of
      hypertension or reducing albuminuria in selected patients.

PMID- 17225722
TI  - Incidence and characteristics of biphasic anaphylaxis: a prospective evaluation
      of 103 patients.
AB  - BACKGROUND: Although it is known that anaphylaxis can follow a biphasic course,
      reports of its incidence are conflicting. Furthermore, little is known about
      predictors of biphasic reactivity. OBJECTIVE: To describe the incidence and
      characteristics of biphasic anaphylaxis occurring in a Canadian tertiary care
      center. METHODS: All patients with emergency department visits and inpatients
      given a diagnosis of "allergic reaction" or "anaphylaxis" during a 3-year period
      were evaluated. Patients were contacted within 72 hours to establish symptoms and
      determine the presence of biphasic reactivity. A full medical record review
      ensued, and uniphasic and biphasic cases were compared using the Mann-Whitney U
      test for continuous data and the chi2 and Fisher exact tests for ordinal data.
      RESULTS: A total of 134 patients with anaphylaxis were identified; complete
      follow-up was obtained for 103 patients. Twenty patients (19.4%) experienced
      confirmed biphasic reactivity. Average time to onset of the second phase was 10
      hours (range, 2-38 hours); 8 patients (40.0%) had their second phase occur more
      than 10 hours after the initial reaction. The clinical presentations and
      histories of uniphasic and biphasic reactors were similar. Time to resolution of
      initial symptoms was significantly longer for biphasic reactors (112 vs 133
      minutes; P = .03). Differences in management were noted: biphasic reactors
      received less epinephrine (P = .048) and tended to receive less corticosteroid (P
      = .06). CONCLUSIONS: Biphasic reactivity occurred with an incidence of 19.4%,
      consistent with first descriptions. The second-phase onset was 10 hours on
      average, but it occurred as late as 38 hours. Biphasic anaphylaxis may be
      related, in part, to undertreatment.

PMID- 17225723
TI  - Association between alcohol consumption and skin prick test reactivity to
      aeroallergens.
AB  - BACKGROUND: A few studies have indicated a positive association between
      consumption of alcohol and allergic sensitization in age and socioeconomically
      heterogeneous populations. OBJECTIVE: To investigate the association between
      consumption of alcohol and allergic sensitization in a young homogenous
      population of high social class (a group with a suspected high prevalence of
      sensitization). METHODS: A total of 1,668 students aged 18 to 35 years recruited
      from universities in Copenhagen, Denmark, underwent skin prick testing (SPT) in
      October or November 2002 and completed a questionnaire about respiratory disease
      and lifestyle habits, including alcohol consumption. SPT positivity was defined
      as a positive reaction (> or =3 mm) against at least 1 of 10 common inhalant
      allergens. RESULTS: Before and after adjustment for sex, age, smoking, atopic
      predisposition, and pet keeping, no significant association was found between
      alcohol consumption (including type of beverage) and SPT positivity. Increasing
      alcohol consumption was significantly negatively associated with asthma symptoms
      and hay fever symptoms. CONCLUSIONS: Alcohol consumption does not favor SPT
      positivity, but cumulated effects were not addressed in the present study.
      Individuals with asthma or hay fever symptoms seem to reduce alcohol intake (a
      healthy drinkers' effect).

PMID- 17225724
TI  - Circadian changes in granulocyte-macrophage colony-stimulating factor message in
      circulating eosinophils.
AB  - BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF), which
      stimulates eosinophil recruitment, activation, and survival, is expressed by
      activated eosinophils. Although eosinophil recruitment and enhanced survival have
      been associated with nocturnal asthma (NA), the contribution of GM-CSF to NA is
      unknown. OBJECTIVE: To determine whether circulating eosinophil GM-CSF expression
      correlates with the symptoms of NA. METHODS: The GM-CSF messenger RNA (mRNA)
      expression at 4 PM and 4 AM was determined by reverse-transcriptase polymerase
      chain reaction with Southern blot analysis in subjects with and without NA and in
      controls. RESULTS: A total of 142 asthma subjects were screened for nocturnal
      asthma with 1-week home peak expiratory flow rate (PEFR) monitoring. Eleven
      subjects had NA (>20% diurnal variation in PEFR on 4 of 7 days), and 6 met the
      criteria for non-NA (<10% diurnal variation in PEFR on 7 of 7 days); 8 controls
      were studied. In subjects with NA, GM-CSF mRNA expression in circulating
      eosinophils increased 3-fold at 4 AM compared with 4 PM. Diurnal changes in GM
      CSF mRNA expression were not detected in the non-NA and control groups.
      CONCLUSIONS: Day-night variation in eosinophil GM-CSF expression is associated
      with circadian variation in airway function in asthma, a key manifestation of
      asthma severity.

PMID- 17225725
TI  - A role for endothelial selectins in allergic and nonallergic inflammatory
      disease.
AB  - BACKGROUND: Several studies indicate that selectin-mediated leukocyte migration
      may depend on the types of initiating inflammatory stimuli or on the vascular
      beds involved in the inflammatory response. Thus, targeting selectin interactions
      to treat inflammation may have variable effects depending on the site and origin
      of the inflammatory response. OBJECTIVE: To address whether selectin-mediated
      leukocyte recruitment is stimulus or tissue dependent. METHODS: We examined
      pulmonary and cutaneous allergic inflammatory responses and silica-induced
      nonallergic lung inflammation and fibrosis in wild-type and P- and E-selectin
      deficient (P/E-/-) double knockout mice. Allergen-sensitized wild-type and P/E-/-
      double knockout mice were challenged either intradermally or via the airways to
      induce allergic responses in the skin or lung, respectively. Other animals were
      subjected to intranasal silica administration to induce a nonallergic lung
      inflammatory/fibrotic response. RESULTS: The P/E-/- mice exhibited significantly
      reduced allergic inflammation in the skin and lung. Allergic late-phase ear
      swelling and allergic lung airway hyperresponsiveness were also significantly
      attenuated in the P/E-/- mice compared with identically treated wild-type
      animals. In contrast, pulmonary inflammation and fibrosis induced by intranasal
      administration of silica particles resulted in a more severe phenotype in the P/E
      /- mice. CONCLUSIONS: Selectin interactions drive allergic inflammation in the
      lung and skin. Silica-induced pulmonary inflammation and fibrosis, however, was
      more pronounced in the absence of selectin interactions, suggesting that selectin
      mediated leukocyte migration may depend on the types of initiating inflammatory
      stimuli.

PMID- 17225726
TI  - Apparent anaphylactoid reaction after treatment with a single dose of
      telithromycin.
AB  - BACKGROUND: Telithromycin, the first ketolide antimicrobial agent available in
      the United States, is related to the macrolide class of antibiotics. Reports of
      immediate-type hypersensitivity reactions with macrolides or ketolides are rare
      overall. OBJECTIVE: To describe a patient with a severe, apparent mast cell
      mediated reaction to telithromycin. METHODS: A 54-year-old woman with a history
      of hypertension was prescribed telithromycin by her primary care physician for
      presumed bacterial sinusitis. Shortly after ingesting the first dose of
      telithromycin she developed severe shortness of breath, wheezing, and angioedema.
      Her allergic history was significant for the development of a maculopapular rash
      after taking sulfonamide antibiotics, but she had received erythromycin and
      azithromycin in the past with no adverse effects. She was intubated with
      difficulty and was treated with epinephrine, diphenhydramine, and
      corticosteroids. The patient made a full recovery. RESULTS: Although not
      confirmed, the patient's severe symptoms were anaphylactoid and were ascribed to
      an immediate-type hypersensitivity reaction to telithromycin. No other causative
      agents, including other drugs, foods, and environmental exposures, were
      implicated in this case. Her history of tolerability to macrolide antibiotics is
      of interest considering the chemical similarities between these drugs and
      telithromycin. CONCLUSION: To our knowledge, this is the first reported case of a
      severe, immediate-type hypersensitivity reaction to telithromycin. Physicians
      prescribing this drug should be aware of this rare but serious effect.

PMID- 17225727
TI  - Seal and whale meat: two newly recognized food allergies.
AB  - BACKGROUND: Alaska's marine mammals compose a large portion of the diet of
      indigenous coastal Alaskan people. Bowhead whales (Balaena mysticetus) and
      bearded seals (Erignathus barbatus), inhabitants of the Bering and Beaufort seas
      along Alaska's western and northern coasts, are 2 of the most important
      subsistence species, serving as major food sources to the native population.
      OBJECTIVE: To describe an Inupiaq boy with symptoms consistent with an IgE
      mediated food allergy after ingestion of bowhead whale and bearded seal meat.
      METHODS: Extracts of cooked bowhead whale and bearded seal were prepared,
      lyophilized, and evaluated for protein content. Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis was performed for each extract, followed by
      transfer to nitrocellulose and IgE immunoblots. Skin prick testing was conducted
      using reconstituted extracts of 1:10 wt/vol dilution. RESULTS: Immunoblots
      revealed serum specific IgE binding with the extracts of bowhead whale and
      bearded seal meat. Protein bands of approximately 25, 40, 50, and 90 kDa were
      found in the seal meat. Protein bands of 55 and 90 kDa were found in the whale
      meat. Skin prick test results were positive to whale and seal extracts with
      appropriate positive and negative controls. Ten control subjects had negative
      reactions to both extracts. CONCLUSION: A patient with moderate anaphylaxis to
      bowhead whale and bearded seal meat demonstrated serum specific IgE by means of
      immunoblot and positive skin prick test results. This is the first known reported
      case of specific IgE to these species.

PMID- 17225728
TI  - Are safety needles safer than traditional needles?

PMID- 17225729
TI  - Exercise-induced anaphylaxis caused by wheat during specific oral tolerance
      induction.

PMID- 17225730
TI  - Allergic contact stomatitis from orthodontic rubber bands.

PMID- 17225731
TI  - Beta2-agonists and paresthesias in multiple sclerosis.

PMID- 17225732
TI  - [Acute ST-segment elevation also possible in non-coronary disorders].
AB  - Three patients were referred with symptoms of acute coronary syndrome. The ECG
      results indicated ST-segment elevation. A 39-year-old man had normal coronary
      arteries and was eventually diagnosed with pericarditis and myocarditis. A 71
      year-old woman had ST-segment elevation caused by mechanical pressure from a
      chest drain that was inserted for a pneumothorax. A 62-year-old man was admitted
      to the intensive care unit and was found to have ST-segment elevation related to
      sepsis and non-significant coronary artery disease. All 3 patients recovered
      following adequate treatment. Percutaneous coronary intervention is the first
      choice therapy for ST-segment elevation myocardial infarction (STEMI). However,
      ST-segment elevation can also occur in patients with non-coronary disorders.
      Clinicians should be encouraged to scrutinise 'STEMI' as a referral diagnosis and
      check if there are signs of coronary mimicry, i.e. ECG changes due to a non
      coronary underlying cause. The ECG changes should be considered in relation to
      the clinical data at presentation, rather than interpreted as a single diagnostic
      finding.

PMID- 17225733
TI  - [Progress and clashes in stem cell therapy research].
AB  - The concept of stem cell therapy, the repair of damaged or diseased tissue by
      transplantation of healthy cells, is deceptively simple. This simplicity has led
      to the hype among desperate patients, their doctors and the media: it would seem
      that every ailment can be treated with stem cells. At this time, however, the
      scientific truth is mostly disappointing. The recent claim from Korea of a major
      breakthrough - the ability to grow stem cells from cloned embryos - turned out to
      be fraudulent. With the exception ofapplications in haematologic diseases, skin
      wounds, and bone and cartilage diseases, most of the putative therapeutic
      applications of stem cell therapy are still under preclinical investigation.
      These include the treatment of Parkinson's and Alzheimer's disease, paraplegia,
      cerebral infarction, amyotrophic lateral sclerosis, multiple sclerosis and
      muscular dystrophy. The treatment of cardiac infarction is currently being
      investigated in clinical trials.

PMID- 17225734
TI  - [The immune system of the skin and stereotyped reaction patterns in inflammatory
      skin diseases].
AB  - The clinical and histological presentation of inflammatory disease in the skin is
      exceedingly heterogeneous. Nonetheless, most inflammatory dermatoses can be
      classified according to five stereotypical tissue-reaction patterns: the
      spongiotic, the lichenoid, the psoriasiform, the vesiculo-bullous and the
      vasculopathic. By means of potent antigen-presenting cells, cytokine and
      chemokine cascades and a skin-specific cutaneous lymphocyte antigen (CLA)
      positive lymphocyte population, the skin is able to respond very efficiently to
      pathogens that threaten the individual. Inflammatory skin diseases follow the
      rules and routes of the physiological reaction to inflammation but however for
      various reasons the immune response may be inadequate, enhanced or chronic. In
      allergic contact dermatitis, which is a prototype of the spongiotic reaction
      pattern, the inflammation is directed against an otherwise harmless antigen, for
      which the body is sensibilized. Lichenoid dermatitis (like erythema multiforme,
      graft versus host disease or lupus erythematodes) is based on a primary cytotoxic
      reaction against the basal epithelial cell, due to alterations in its antigenic
      make-up or due to an altered immune response. In psoriasis, an example of
      psoriasiform dermatitis, the interaction between inflammatory cells, antigen
      presenting cells and epithelial cells is disturbed.

PMID- 17225735
TI  - [Increasing role for angiographic embolisation in the treatment of
      gastrointestinal haemorrhage].
AB  - Endoscopy is the primary diagnostic and therapeutic modality for the vast
      majority of patients with haemorrhage of the upper or lower digestive tract. In
      many hospitals, surgery is the therapy of choice when endoscopy fails or is
      impossible. In patients who have considerable co-morbidity and who are actively
      bleeding from the digestive tract, surgery is associated with a relatively high
      morbidity and mortality. Angiographic embolisation for haemorrhage from the upper
      or lower digestive tract is effective, with success rates varying from 50 to 90%.
      The risk of ischaemic complications of the procedure is acceptably low (< 5%).
      Angiography is not very time-consuming and does not preclude subsequent surgical
      treatment ifangiographic embolisation does not succeed. However, performing
      embolisation requires skill and experience and the procedure is not available
      everywhere. Angiographic embolisation is a valuable alternative to surgery and
      should be considered in all patients with haemorrhage of the digestive tract who
      cannot be treated by means of endoscopy.

PMID- 17225736
TI  - [Diagnostic image (272). A boy with discoloured, painful hands].
AB  - A 6-year-old boy was admittted because of dark discoloured and painful finger
      tips of both hands, which had developed 2 weeks after playing with bare hands in
      a ditch with cold water still containing parts of ice. Trench foot of the hands
      was diagnosed.

PMID- 17225737
TI  - [Compliance with the breast cancer guidelines in the region of the Comprehensive
      Cancer Centre South, 20031/'04].
AB  - OBJECTIVE: To examine the level of compliance with the NABON-guidelines (i.e.
      breast cancer consensus recommendations) issued in 1999 with particular regard to
      the diagnostics and treatment of breast cancer in hospitals in the region covered
      by the Comprehensive Cancer Centre South (covering the Noord-Brabant and Noord
      Limburg areas in the Netherlands). DESIGN: Retrospective, descriptive. METHOD:
      Using the Cancer Registry, the average number ofbreast cancer patients in 16
      general hospital locations in the region covered by the Comprehensive Cancer
      Centre South was determined. Then, from I July 2003 to 30 June 2004, at each
      hospital location, all successive patients in whom carcinoma of the breast
      (invasive or in situ) had been diagnosed were included until one-third of the
      annual total was reached. Data from the medical-case notes of these patients were
      collected in order to examine to what extent the hospital locations had complied
      with the NABON-norms. RESULTS: A total of 581 breast cancer patients were
      included. In general the diagnostics and treatment complied with the consensus
      recommendations in the NABON-policy document. Improvements were mainly indicated
      in the area of logistics. One hospital met the guideline's recommendation that in
      90% of cases, the pathology department should ensure that the results ofa
      histological needle-biopsy are available within 2 days of the biopsy being
      carried out. In 62% of patients, surgery was performed within 3 weeks of the
      necessity of an operation being confirmed, although the target norm was 90%. The
      interval between the last operation and the start of radiotherapy treatment was
      44 instead of the proposed 28 days. Inter-hospital differences in diagnostics
      were seen mainly in the application of sentinel-node biopsy (34-95%).
      Furthermore, broad diversity was observed in the percentage of patients treated
      in the proposed space oftime between pathology result and initial surgery (3-87%)
      and between the last operation and start ofradiotherapy (0-46%) or chemotherapy
      (0-100%).

PMID- 17225738
TI  - [Cerebral infarction due to polycythaemia as the initial manifestation of renal
      cell carcinoma].
AB  - A 65-year-old man with known diabetes mellitus and hypertension (cardiovascular
      risk factors) presented to the Emergency Clinic with a transient language
      disorder and motor- and cognitive-function disorders that had been present for
      the past half a year. Brain imaging revealed multiple white-matter lesions and a
      recent infarction. Routine blood tests revealed polycythaemia. Further tests
      revealed an elevated erythropoietin level and bilateral renal tumours. The
      cognitive functions improved after repeated phlebotomies and surgical resection
      of the renal-cell carcinomas. Before surgery, transcranial ultrasound had shown
      very low cerebral flow velocities, which became normal after correction of the
      haematocrit. This case emphasises the importance of routine blood tests in
      patients with suspected cerebral infarction. To our knowledge, this is the first
      case of cerebral infarction as the first manifestation ofa renal-cell carcinoma.

PMID- 17225739
TI  - [Septic polyarthritis due to an infected nail bed around an ingrown toenail in a
      previously healthy boy].
AB  - A 17-year-old, previously healthy boy was admitted with complaints of fever,
      malaise and pain in the pubic region and groin. His left elbow was also warm and
      swollen and could not be extended fully. Cultures of fluid drained from both hips
      and the elbow, blood and inflamed tissue from the nail bed of the right big toe
      yielded Staphylococcus aureus. The patient was treated with intravenous
      antibiotics for septic arthritis of both hips, the left elbow and possibly the
      pubic symphysis. The infected nail bed, which was the most likely port of entry,
      was also treated. One year later, the original painful symptoms had disappeared
      but the right hip was almost immobile. In a patient with indications of septic
      arthritis, timely diagnosis and adequate therapy reduce the risk of permanent
      damage to the joint.

PMID- 17225740
TI  - [Intoxication due to replacement of the precursor methylphenobarbital by
      phenobarbital].
AB  - An 80-year-old woman with a history of familial primary generalised epilepsy
      presented to the outpatient clinic with complaints of dizziness, confusion,
      dullness and feeling of'being worthless'. It turned out that she had been using
      medication for some time in which the chemical nature of the pharmacologically
      active ingredient had been changed: methylphenobarbital 60 mg t.i.d. had been
      replaced by phenobarbital 60 mg t.i.d. The resultant phenobarbital concentration
      was much higher than the concentration to which she was accustomed. At the same
      dosage, phenobarbital is more active than methylphenobarbital. When one compound
      ofa pharmacologically active substance is replaced by a different compound, the
      dosage should be corrected for both the chemical structure, such as the molecular
      weight, and the pharmacokinetic properties such as absorption, metabolism and
      biological availability.

PMID- 17225741
TI  - [Computers do not improve undergraduate medical education].
AB  - There is no convincing evidence that computer-assisted learning (CAL) leads to
      better doctors. Apprenticeships supervised by expert teachers are a time-honoured
      and effective way to educate future doctors. Medical faculties should not invest
      in CAL at the expense of properly supervised clerkships.

PMID- 17225742
TI  - [Good medical education is impossible without computers].
AB  - Computers are medical instruments, for which reason they must be included in the
      medical curriculum. As educational tools, electronic teaching environments,
      multimedia applications and computers stimulate self-study. Moreover, computers
      make the medical literature readily accessible and facilitate the administration
      of the training programme. They are thus an indispensable part of medical
      education, and of academic and student administration.

PMID- 17225743
TI  - [A patient with serious viral myositis following flu].

PMID- 17225744
TI  - [Complete atrioventricular block during galantamine therapy].

PMID- 17225745
TI  - [Diagnosis image (255). A woman with a painful hand after plaster treatment].

PMID- 17225747
TI  - Falls prevention and Alzheimer's.

PMID- 17225746
TI  - Providers upgrade buildings, expand services.

PMID- 17225748
TI  - Financing LTC with life insurance.

PMID- 17225754
TI  - [Eating disorders in diabetic patients].

PMID- 17225756
TI  - [Chronic obstructive lung disease, from screening to care].

PMID- 17225755
TI  - [Confidentiality and professional secrecy in health establishments].

PMID- 17225757
TI  - [Understanding, preventing and better caring for chronic obstructive lung
      disease].

PMID- 17225758
TI  - [Respiratory tract and physiopathology in chronic obstructive lung disease].

PMID- 17225759
TI  - [From early diagnosis to disability, how to slow the progression of chronic
      obstructive lung disease?].

PMID- 17225761
TI  - [Support care and chronic obstructive lung disease, how to care in other ways?].

PMID- 17225760
TI  - [Screening of chronic obstructive lung disease and education of health
      professionals].

PMID- 17225762
TI  - [Nursing consultation, first encounter in a long term relationship].

PMID- 17225763
TI  - [Inhalation therapy, method of use].

PMID- 17225764
TI  - [Smoking cessation, to better combat chronic obstructive lung disease].

PMID- 17225766
TI  - [Chronic obstructive lung disease and home care nurses, from preventive care to
      palliative care].

PMID- 17225765
TI  - [Smoking cessation specialist nurse].

PMID- 17225767
TI  - [Palliative management of the patient with respiratory insufficiency].

PMID- 17225768
TI  - [The French Association of Patients with Respiratory Insufficiency].

PMID- 17225769
TI  - [Yolande, an ordinary day of a respiratory insufficiency patient].

PMID- 17225770
TI  - [The "patient teacher", or how to teach one's own experience].

PMID- 17225771
TI  - [9/10 Avoiding grave undesirable events related to temporary staffing by
      improving professional practices].

PMID- 17225772
TI  - And the wheel goes 'round and 'round...

PMID- 17225773
TI  - The Trojan horse.

PMID- 17225774
TI  - House calls or "concierge medicine".

PMID- 17225775
TI  - Elections 2006: more crucial than ever.

PMID- 17225776
TI  - Causation question.

PMID- 17225777
TI  - Residency stress.

PMID- 17225778
TI  - Nuclear options: why there will be a fire sale on nuclear imaging equipment in
      2006.

PMID- 17225779
TI  - Epitrochlear lymph node: an unusual physical finding in lymphoma with important
      clinical significance.

PMID- 17225780
TI  - Drug modified arrhythmia: what's your diagnosis?

PMID- 17225781
TI  - Constitutional right to the insanity defense?

PMID- 17225782
TI  - Health of Nashville, 1814.

PMID- 17225783
TI  - [A meningioma resulting in drastic changes in behavior and life course].
AB  - Three patients, a 59-year-old woman, a 51-year-old man and a 66-year-old woman
      presented at a neurological or neurosurgical outpatient clinic after their lives
      had been drastically affected by behavioural changes. Neither the patients nor
      their relatives or friends were aware that the behavioural changes may be caused
      by a medical problem. The cause, a large meningioma, became obvious only after
      physical symptoms occurred a few years later. The patients recovered after
      surgery and regretted having made certain decisions with far-reaching
      repercussions for their lives and families. Behavioural disturbances are seldom
      due to slowly growing brain tumours, but consultation with a neurologist is
      recommended if there is any doubt regarding the possibility of somatic causes.

PMID- 17225784
TI  - [Screening the population for colorectal cancer: the background to a number of
      pilot studies in the Netherlands].
AB  - Colorectal cancer is one of the most common cancers in the Netherlands, where it
      is now the second most commonly-occurring cancer in terms of both incidence
      (10,000 new cases each year) and mortality rate (4,400 each year). - In 40% of
      all cases the disease is diagnosed at a late stage, which is associated with a
      poor outcome. - Research has shown that screening of the general population for
      colorectal cancer by means of the faecal occult blood test (FOBT) results in a
      reduction in mortality of approximately 16%. Whether endoscopic screening will
      result in a greater reduction in the mortality rate is currently under
      investigation. - This year, the first pilot study on implementation of screening
      for colorectal cancer using two different types of FOBT will start in the
      Netherlands.

PMID- 17225785
TI  - [Perioperative nutrition].
AB  - Illness is associated with involuntary weight loss, which is often the result of
      malnutrition. The undernourished surgical patient runs a higher risk of
      postoperative morbidity and mortality. For this reason, perioperative nutrition
      is an important part of a patient's therapy. Supplying substrates for wound
      healing and maintaining existing organic structures are the major goals of
      nutrition. It is recommended that extremely malnourished patients be fed at least
      7 days prior to surgery. It would seem sensible to give a carbohydrate-rich
      beverage up to 2 hours before surgery, both to decrease preoperative anxiety and
      to reduce postoperative insulin resistance. The Dutch tradition of fasting
      patients before surgery is difficult to defend any longer because this policy
      impairs patients' state of health as a result of which they are not optimally
      prepared for the surgical induced stress response. The postoperative recovery of
      all surgical patients can be improved by an early postoperative start of enteric
      nutrition. When the enteric administration of food turns out to be impossible,
      total parenteral nutrition can be given to bridge a long period without food.

PMID- 17225786
TI  - [From the Cochrane Library: both expectant management and curettage are suitable
      options in case of miscarriage].
AB  - A Cochrane systematic review of 5 randomised clinical trials compared the safety
      and efficacy of expectant management versus curettage for early foetal loss. The
      expectant-care group was more likely to have an incomplete miscarriage, a need of
      unplanned curettage, and bleeding. In contrast, curettage was associated with a
      significantly higher risk ofinfection. Given the lack of clear superiority of
      either approach, the woman's preference should play a dominant role in reaching a
      decision.

PMID- 17225787
TI  - [New drugs; palifermin].
AB  - Palifermin is a human keratinocyte growth factor that is produced in Escherichia
      coli by recombinant-DNA-technology. This substance protects against oral
      mucositis in adults undergoing myeloablative therapy. The safety of this product-
      being a growth factor --in the long term has not yet been shown. Adverse effects
      may occur in the skin and mucous membranes.

PMID- 17225788
TI  - [Diagnostic image (304). A woman with microcalcifications at mammography].
AB  - A 72-year-old woman had temporary microcalcifications in the nipple area at
      mammography, possibly caused by skin care products.

PMID- 17225789
TI  - [The anatomy lesson of Dr Nicolaes Tulp by Rembrandt (1632) and the findings
      during dissection of the forearm of a cadaver: anatomical discrepancies].
AB  - OBJECTIVE: To compare The anatomy lesson of Dr Nicolaes Tulp by Rembrandt (1632)
      with the findings during dissection of the forearm of a cadaver. DESIGN:
      Descriptive. METHOD: The left forearm of a 41-year-old white male cadaver was
      dissected, photographs being taken at every stage of dissection. The anatomical
      structures in the original painting and during dissection were described and
      compared. At dissection, several structures were displaced in an attempt to
      reproduce the anatomical structures as shown in the painting. RESULTS: Dissection
      revealed four anatomical differences in comparison with Rembrandt's painting: (a)
      the muscle belly seen at the proximal ulnar side of the forearm in the painting
      was not seen on dissection; section of the insertion of the M. flexor carpi
      radialis and transposition of this muscle to the location of the muscle belly
      created the possibility of lifting up the M. flexor digitorum superficialis and
      reproducing the muscle belly; (b) in the painting, Tulp lifted only the M. flexor
      digitorum superficialis, but the amount of muscle tissue found in the forceps was
      increased in the painting compared with the dissection; (c) the positions of the
      bellies of the M. flexor digitorum superficialis to the index finger and 5th
      digit and to the 3rd and 4th digits were found to be reversed; (d) the
      longitudinal white structure situated in the ulnar part of the 5th digit in the
      painting was not found on dissection. This may have been an anatomical variant of
      the ulnar nerve. CONCLUSION: The anatomical characteristics of the painting could
      not be reproduced by dissection of the forearm of a cadaver.

PMID- 17225790
TI  - [Fever of unknown origin caused by anaplasmosis].
AB  - A 74-year-old man in good clinical condition presented with complaints of
      recurrent fever up to 38 degrees C and diffuse thoracic pain, both present for
      several weeks. Antibiotic therapy did not result in disappearance of the
      symptoms. Except for a picture of chronic inflammation and a positive Anaplasma
      IgM antibody titre, serology yielded no indication ofthe diagnosis. Further
      investigation, including imaging, showed no convincing cause. 'Anaplasma
      infection' remained the working diagnosis. One month after hospitalisation, the
      patient was free of fever without any type of therapy. Control blood tests
      revealed seroconversion to Anaplasma IgG antibodies, constituting serological
      evidence of a recent infection. The prevalence ofanaplasmosis is increasing. Mice
      are the principal reservoir for the intracellular bacteria and the infection is
      transmitted by ticks. In case of fever of unknown origin, since the transmission
      takes place in the same manner, one should consider both Borrelia and an
      infection with Anaplasma.

PMID- 17225791
TI  - [Two patients with lactic acidosis and hypoglycaemia as initial presentation of a
      lymphoma].
AB  - A 32-year-old man who had undergone kidney transplantation presented with
      malaise, severe diarrhoea, nausea and vomiting, productive cough and shortness of
      breath. A 42-year-old woman with no relevant medical history presented with
      fever, weight loss and abdominal pain. Both patients had lactic acidosis and
      hypoglycaemia. Initially, the hyperlactataemia was thought to result from tissue
      hypoxia (sepsis) but it persisted after correction of the hypovolaemia;
      therefore, alternative causes were considered. Both patients were found to have T
      cell lymphoma with liver infiltration. The male patient died before treatment
      could be initiated. The lactic acidosis resolved in the female patient following
      lymphoma treatment, but she died subsequently from the lymphoma. Lymphoreticular
      malignancies should be considered for cases of lactic acidosis with sufficient
      oxygen supply, particularly when hypoglycaemia is also present. The lactic
      acidosis and hypoglycaemia result from increased anaerobic glycolysis in tumour
      cells. Tumour reduction with chemotherapy can reduce the lactic acidosis.

PMID- 17225792
TI  - [The introduction of antiretroviral therapy in Malawi].
AB  - The prevalence of HIV infection in Malawi is high. Until mid 2004, antiretroviral
      therapy (ART) was only available for a fee; later, a programme for free
      distribution was started. When ART was started, no laboratory tests other than an
      HIV test were felt to be necessary. After an introductory period in which
      hospitals were assessed for the presence of sufficient infrastructure and health
      workers were trained in ART, the number of public and private clinics where ART
      was distributed rose to 60. By end 2005, the number of patients on ART was
      37,840, which is 45% of the target in the so-called '3-by-5' initiative of the
      WHO/Joint United Nations Programme on HIV/ AIDS (UNAIDS). The goal of this
      initiative was to have half (85,000) ofthe estimated 170,000 HIV-infected
      individuals in Malawi for whom ART is indicated on treatment by end 2005. After
      12 months of follow-up, 81% of the patients treated were still alive and on
      treatment, while the mortality was 10%, 8% no longer visited the outpatient
      clinic, and 1% had stopped ART. Despite facing various challenges, intensive
      collaboration with all stakeholders involved, under strong leadership of the
      Ministry of Health, has laid the foundation for this thus far successful
      programme.

PMID- 17225793
TI  - [Melatonin: physiological and pathophysiological aspects and possible
      applications].

PMID- 17225794
TI  - [Melatonin: physiological and pathophysiological aspects and possible
      applications].

PMID- 17225795
TI  - Piezoelectric thin films: evaluation of electrical and electromechanical
      characteristics for MEMS devices.
AB  - We present a new measurement method to characterize piezoelectric thin films
      utilizing a four-point bending setup. In combination with a single- or a double
      beam laser interferometer, this setup allows the determination of the effective
      transverse and longitudinal piezoelectric coefficients e31,f and d33,f,
      respectively. Additionally, the dielectric coefficient and the large signal
      electrical polarization are measured to add further important characteristics of
      the film. These data are essential for piezoelectric thin film process
      specification and the design and qualification of microelectromechanical systems
      devices.

PMID- 17225796
TI  - On the 1/f frequency noise in ultra-stable quartz oscillators.
AB  - The frequency flicker of an oscillator, which appears as a 1/f3 line in the phase
      noise spectral density, and as a floor on the Allan deviation plot, originates
      from two basic phenomena, namely, (1) the 1/f phase noise turned into 1/f
      frequency noise via the Leeson effect, and (2) the 1/f fluctuation of the
      resonator natural frequency. The discussion on which is the dominant effect, thus
      on how to improve the stability of the oscillator, has been going on for years
      without giving a clear answer. This article tackles the question by analyzing the
      phase noise spectrum of several commercial oscillators and laboratory prototypes,
      and demonstrates that the fluctuation of the resonator natural frequency is the
      dominant effect. The investigation method starts from reverse engineering the
      oscillator phase noise in order to show that if the Leeson effect was dominant,
      the resonator merit factor Q would be too low as compared to the available
      technology.

PMID- 17225797
TI  - Three-dimensional spatial and temporal temperature imaging in gel phantoms using
      backscattered ultrasound.
AB  - Thermal therapies such as radio frequency, heated saline, and high-intensity
      focused ultrasound ablations are often performed suboptimally due to the
      inability to monitor the spatial and temporal distribution of delivered heat and
      the extent of tissue necrosis. Ultrasound-based temperature imaging recently was
      proposed as a means to measure noninvasively the deposition of heat by tracking
      the echo arrival time shifts in the ultrasound backscatter caused by changes in
      speed of sound and tissue thermal expansion. However, the clinical applicability
      of these techniques has been hampered by the two-dimensional (2-D) nature of
      traditional ultrasound imaging, and the complexity of the temperature dependence
      of sound speed for biological tissues. In this paper, we present methodology,
      results, and validation of a 3-D spatial and temporal ultrasound temperature
      estimation technique in an alginate-based gel phantom to track the evolution of
      heat deposition over a treatment volume. The technique was experimentally
      validated for temperature rises up to approximately 10 degrees C by comparison
      with measurements from thermocouples that were embedded in the gel. Good
      agreement (rms difference = 0.12 degrees C, maximum difference = 0.24 degrees C)
      was observed between the noninvasive ultrasound temperature estimates and
      thermocouple measurements. Based on the results obtained for the temperature
      range studied in this paper, the technique demonstrates potential for
      applicability in image guidance of thermal therapy for determining the location
      of the therapeutic focal spot and assessing the extent of the heated region at
      subablative intensities.

PMID- 17225798
TI  - The impact of aberration on high frame rate cardiac B-mode imaging.
AB  - In echocardiography, especially in 3D echocardiography, achieving high frame
      rates is a major challenge. A suggested solution is parallel receive beamforming.
      Without any compensation, this approach is known to produce block-like artifacts,
      where each block corresponds to one parallel receive group. In this work, in
      vitro imaging, in vivo imaging, and simulations were used to investigate the
      artifacts. In vitro, imaging a tissue phantom, the artifacts were successfully
      compensated for. However, in vivo, imaging the heart, the compensation techniques
      no longer sufficed and the artifacts persisted. With in vivo imaging, aberrating
      tissue layers are present between the heart and the probe. To investigate the
      effects of aberration on a parallel receive system, an in vitro experiment was
      performed with and without a silicon phase aberrator in front of the probe. The
      aberrator caused the artifacts to appear even when compensation techniques were
      applied. Simulations confirmed the measured results and indicated that distorted
      beam profiles and decorrelation between parallel receive groups caused the
      artifacts. To quantify the magnitude of the artifacts, a correlation-based
      indicator was developed. The indicator separated images with and without
      artifacts and confirmed that the artifacts appeared from the combination of
      parallel receive beams and aberration.

PMID- 17225799
TI  - Implementation of the near-field signal redundancy phase-aberration correction
      algorithm on two-dimensional arrays.
AB  - Near-field signal-redundancy (NFSR) algorithms for phase-aberration correction
      have been proposed and experimentally tested for linear and phased one
      dimensional arrays. In this paper the performance of an all-row-plus-two-column,
      two-dimensional algorithm has been analyzed and tested with simulated data sets.
      This algorithm applies the NFSR algorithm for one-dimensional arrays to all the
      rows as well as the first and last columns of the array. The results from the two
      column measurements are used to derive a linear term for each row measurement
      result. These linear terms then are incorporated into the row results to obtain a
      two-dimensional phase aberration profile. The ambiguity phase aberration profile,
      which is the difference between the true and the derived phase aberration
      profiles, of this algorithm is not linear. Two methods, a trial-and-error method
      and a diagonal-measurement method, are proposed to linearize the ambiguity
      profile. The performance of these algorithms is analyzed and tested with
      simulated data sets.

PMID- 17225800
TI  - Modeling prostate anatomy from multiple view TRUS images for image-guided HIFU
      therapy.
AB  - Current planning methods for transrectal high-intensity focused ultrasound
      treatment of prostate cancer rely on manually defining treatment regions in 15-20
      sector transrectal ultrasound (TRUS) images of the prostate. Although effective,
      it is desirable to reduce user interaction time by identifying functionally
      related anatomic structures (segmenting), then automatically laying out treatment
      sites using these structures as a guide. Accordingly, a method has been developed
      to effectively generate solid three-dimensional (3-D) models of the prostate,
      urethra, and rectal wall from boundary trace data. Modeling the urethra and
      rectal wall are straightforward, but modeling the prostate is more difficult and
      has received much attention in the literature. New results presented here are
      aimed at overcoming many of the limitations of previous approaches to modeling
      the prostate while using boundary traces obtained via manual tracing in as few as
      5 sector and 3 linear images. The results presented here are based on a new type
      of surface, the Fourier ellipsoid, and the use of sector and linear TRUS images.
      Tissue-specific 3-D models will ultimately permit finer control of energy
      deposition and more selective destruction of cancerous regions while sparing
      critical neighboring structures.

PMID- 17225801
TI  - Estimating the blood velocity vector using aperture domain data.
AB  - Most conventional blood flow estimation methods measure only the axial component
      of the blood velocity vector. In this study, we developed a new method for two
      dimensional (2-D) velocity vector estimation in which time shifts resulting from
      blood motion are calculated for the individual channels using aperture domain
      data. This allows the construction of a time-shift profile along the array
      direction as a function of channel index, which is approximated by a first-order
      polynomial whose zeroth-order and first-order terms can be used to determine the
      axial and lateral velocity components, respectively. The efficacy of the proposed
      method was verified by simulations and experiments in which the transducer array
      had 64 elements, an aperture size of 1.96 cm, and a center frequency of 5 MHz.
      The flow velocity ranged from 5 to 35 cm/s and the Doppler angle ranged from 0
      degrees to 90 degrees. The experimental results show that the accuracy of axial
      velocity estimation is higher for the new method than for the autocorrelation
      based conventional method when the signal-to-noise ratio is larger than 0 dB. The
      mean estimation error for the axial velocity component is 2.18% for the new
      method, compared to 4.51% for the conventional method. The mean estimation error
      for the lateral velocity component is 15%, which is comparable to existing
      methods.

PMID- 17225802
TI  - Novel transmit protection scheme for ultrasound systems.
AB  - The problem of protecting or isolating extremely sensitive receive circuitry from
      high-voltage transmit circuitry is commonly addressed through the use of diode
      bridges, transformers, or high-voltage switches, which prove to be prohibitively
      expensive, bulky, and power consuming for use in portable, low-cost, battery
      powered systems. These approaches also compound the interconnect difficulties
      associated with two-dimensional (2-D) transducer arrays. In this paper we present
      a novel transmit protection scheme that allows compact MOSFET shunting devices to
      be brought on-chip within each receive channel implemented in a standard CMOS
      integrated circuit process. During transmit, the high voltage transmit pulse is
      driven onto the common connection of the transducer array and the on-chip MOSFET
      devices shunt the current to ground. During receive, these devices are turned
      off, the common connection of the transducer array is shunted to ground, and the
      received echo can be detected as usual. The transmit protection scheme was
      experimentally shown to shunt a 16 mA peak current resulting from the equivalent
      of a 100-V, 25-ns-risetime transmit pulse through a 4 pF transducer element. The
      scheme was also incorporated into a prototype 1024-channel, low-cost, ultrasound
      system successfully used to form pulse echo images.

PMID- 17225803
TI  - Micromachined thin film plate acoustic resonators utilizing the lowest order
      symmetric lamb wave mode.
AB  - Thin film integrated circuits compatible resonant structures using the lowest
      order symmetric Lamb wave propagating in thin aluminum nitride (AlN) film
      membranes have been studied. The 2-microm thick, highly coriented AlN
      piezoelectric films have been grown on silicon by pulsed, direct-current
      magnetron reactive sputter deposition. The films were deposited at room
      temperature and had typical full-width, half-maximum value of the rocking curve
      of about 2 degrees. Thin film plate acoustic resonators were designed and
      micromachined using low resolution photolithography and deep silicon etching.
      Plate waves, having a 12-microm wavelength, were excited by means of both
      interdigital (IDT) and longitudinal wave transducers using lateral field
      excitation (LW-LFE), and reflected by periodical aluminum-strip gratings
      deposited on top of the membrane. The existence of a frequency stopband and
      strong grating reflectivity have been theoretically predicted and experimentally
      observed. One-port resonator designs having varying cavity lengths and transducer
      topology were fabricated and characterized. A quality factor exceeding 3000 has
      been demonstrated at frequencies of about 885 MHz. The IDT based film plate
      acoustic resonators (FPAR) technology proved to be preferable when lower costs
      and higher Qs are pursued. The LW-LFE-based FPAR technology offers higher
      excitation efficiency at costs comparable to that of the thin film bulk acoustic
      wave resonator (FBAR) technology.

PMID- 17225804
TI  - Numerical analysis of strongly nonlinear extensional vibrations in elastic rods.
AB  - In the framework of transduction, nondestructive testing, and nonlinear acoustic
      characterization, this article presents the analysis of strongly nonlinear
      vibrations by means of an original numerical algorithm. In acoustic and
      transducer applications in extreme working conditions, such as the ones induced
      by the generation of high-power ultrasound, the analysis of nonlinear ultrasonic
      vibrations is fundamental. Also, the excitation and analysis of nonlinear
      vibrations is an emergent technique in nonlinear characterization for damage
      detection. A third-order evolution equation is derived and numerically solved for
      extensional waves in isotropic dissipative media. A nine-constant theory of
      elasticity for isotropic solids is constructed, and the nonlinearity parameters
      corresponding to extensional waves are proposed. The nonlinear differential
      equation is solved by using a new numerical algorithm working in the time domain.
      The finite-difference numerical method proposed is implicit and only requires the
      solution of a linear set of equations at each time step. The model allows the
      analysis of strongly nonlinear, one-dimensional vibrations and can be used for
      prediction as well as characterization. Vibration waveforms are calculated at
      different points, and results are compared for different excitation levels and
      boundary conditions. Amplitude distributions along the rod axis for every
      harmonic component also are evaluated. Special attention is given to the study of
      high-amplitude damping of vibrations by means of several simulations. Simulations
      are performed for amplitudes ranging from linear to nonlinear and weak shock.

PMID- 17225805
TI  - Effects of a parallel resistor on electrical characteristics of a piezoelectric
      transformer in open-circuit transient state.
AB  - This paper investigates electrical transient characteristics of a Rosen-type
      piezoelectric transformer (PT), including maximum voltages, time constants,
      energy losses and average powers, and their improvements immediately after
      turning OFF. A parallel resistor connected to both input terminals of the PT is
      needed to improve the transient characteristics. An equivalent circuit for the PT
      is first given. Then, an open-circuit voltage, involving a direct current (DC)
      component and an alternating current (AC) component, and its related energy
      losses are derived from the equivalent circuit with initial conditions. Moreover,
      an AC power control system, including a DC-to-AC resonant inverter, a control
      switch and electronic instruments, is constructed to determine the electrical
      characteristics of the OFF transient state. Furthermore, the effects of the
      parallel resistor on the transient characteristics at different parallel
      resistances are measured. The advantages of adding the parallel resistor also are
      discussed. From the measured results, the DC time constant is greatly decreased
      from 9 to 0.04 ms by a 10 k(omega) parallel resistance under open output.

PMID- 17225806
TI  - Inverse wave field extrapolation: a different NDI approach to imaging defects.
AB  - Nondestructive inspection (NDI) based on ultrasound is widely used. A relatively
      recent development for industrial applications is the use of ultrasonic array
      technology. Here, ultrasonic beams generated by array transducers are controlled
      by a computer. This makes the use of arrays more flexible than conventional
      single-element transducers. However, the inspection techniques have principally
      remained unchanged. As a consequence, the properties of these techniques, as far
      as characterization and sizing are concerned, have not improved. For further
      improvement, in this paper we apply imaging theory developed for seismic
      exploration of oil and gas fields on the NDI application. Synthetic data obtained
      from finite difference simulations is used to illustrate the principle of
      imaging. Measured data is obtained with a 64-element linear array (4 MHz) on a 20
      mm thick steel block with a bore hole to illustrate the imaging approach.
      Furthermore, three examples of real data are presented, representing a lack of
      fusion defect, a surface breaking crack, and porosity.

PMID- 17225807
TI  - A new elastic-wave-based imaging method for scanning the defects inside the
      structure.
AB  - In this paper, a new nondestructive testing method using elastic waves for
      imaging possible voids or defects in concrete structures is proposed. This method
      integrates the point-source/point receiver scheme with the synthetic aperture
      focusing technique (SAFT) process to achieve the effect like scanning with a
      phase array system. This method also is equipped with large functioning depth
      because of the high-energy feature that elastic waves usually possess over
      traditional ultrasound. Both numerical simulations and experimental tests were
      carried out to explore the capabilities of this method in revealing single or
      multiple defects implied in a matrix material. The results from numerical
      simulations indicate that this method can clearly reveal the number of the voids
      or defects, their locations, and front-end profiles. The influence of the
      accuracy of the wave velocity determination on the resultant image also was
      evaluated in this study. Furthermore, the effects of the types of the responses
      to be recorded and the wavelength of the introduced waves also were evaluated so
      that very good resultant images may be obtained. Both the results from the
      numerical simulations and the experimental tests indicate that this elastic-wave
      based method exhibits high potential in inspecting the defects of in-situ
      concrete structures by imaging.

PMID- 17225808
TI  - Model-based phase velocity and attenuation estimation in wideband ultrasonic
      measurement systems.
AB  - A parametric method to estimate frequency-dependent phase velocity and
      attenuation is presented in this paper. The parametric method is compared with
      standard nonparametric Fourier analysis techniques using numerical simulations as
      well as real pulse-echo experiments. Approximate standard deviations are derived
      for both methods and validated with numerical simulations. Compared to standard
      Fourier analysis, the parametric model gives considerably lower variance when
      estimating attenuation and phase velocity. In contrast to nonparametric
      techniques, the proposed estimator avoids the phase unwrapping problem because
      analytical expressions for the continuous phase velocity and attenuation can be
      derived.

PMID- 17225809
TI  - Generation of narrowband antisymmetric lamb waves using a formed laser source in
      the ablative regime.
AB  - A formed laser source, using a four-element lenticular array, is used in the
      ablative regime to generate select, narrowband, acoustic plate waves. The
      arrangement of the array produces acoustical signals that have frequencies
      compatible with the response of the broadband capacitive air-coupled transducer
      used in this study. A simplified concept is presented to explain the effect of a
      line array source on the frequency content of acoustic waves. The analytical
      model for a point pulse surface displacement is derived from the point load
      solution to Lamb's problem. The point pulse displacement elements of a line array
      source are summed mathematically, taking into account all applicable propagation
      modes and dispersion of plate waves. The model considers only the out-of-plane
      displacement of the antisymmetric plate modes to represent the detection
      capability of the broadband receiver. The distribution function of the laser beam
      energy profile is modified to depict the actual energy distribution that
      illuminates the surface of the plate. Filtering functions are made compatible
      with the sensitivity of the broadband receiver so as to retain only the detected
      frequencies in the model. The theoretical model showed good agreement with
      experimental results.

PMID- 17225810
TI  - Polymer coating behavior of Rayleigh-SAW resonators with gold electrode structure
      for gas sensor applications.
AB  - Results from systematic polymer coating experiments on surface acoustic wave
      (SAW) resonators and coupled resonator filters (CRF) on ST-cut quartz with a
      corrosion-proof electrode structure entirely made of gold (Au) are presented and
      compared with data from similar SAW devices using aluminium (Al) electrodes. The
      recently developed Au devices are intended to replace their earlier Al
      counterparts in sensor systems operating in highly reactive chemical gas
      environments. Solid parylene C and soft poly[chlorotrifluoroethylene-co
      vinylidene fluoride] (PCFV) polymer films are deposited under identical
      conditions onto the surface of Al and Au devices. The electrical performance of
      the Parylene C coated devices is monitored online during film deposition. The
      PCVF coated devices are evaluated after film deposition. The experimental data
      show that the Au devices can stand up to 40% thicker solid films for the same
      amount of loss increase than the Al devices and retain better resonance and phase
      characteristics. The frequency sensitivities of Au and Al devices to parylene C
      deposition are nearly identical. After coating with soft PCFV sensing film, the
      Au devices provide up to two times higher gas sensitivity when probed with
      cooling agent, octane, or tetrachloroethylene.

PMID- 17225811
TI  - SAW filters based on parallel-connected coupled resonator filters with offset
      frequencies.
AB  - The concept of coupled resonators is applied to synthesize surface acoustic wave
      filters. Employing two parallel-connected filter tracks, with a frequency shift
      imposed between them, a wide passband with low insertion loss together with well
      controlled rejections is achieved. The operation of the two-track device is based
      on the mutual interaction of the individual transfer functions for the pair of
      tracks. Each track serves to contribute a part of the passband, enabling a wide
      band. Outside of the passband, the signals passing through the two channels may
      cancel each other, thus facilitating efficient control over the rejections.
      However, obtaining rejection stopbands at just the predetermined frequencies
      requires precise values for the materials parameters and a reliable fabrication
      process. Prototype devices fabricated with this approach are demonstrated both on
      quartz and, for the first time, on 42 degrees-LiTaO3. Results for two-track
      devices having either two or three transducers per track and operating either
      single-ended or with a balanced output are presented. The devices are designed
      employing the coupling-of-modes model and transmission-matrix approach, and the
      separate tracks are optimized simultaneously and independently. The center
      frequencies are 868 MHz and 1960 MHz. On quartz, a minimum insertion loss of 4 dB
      and a passband width of 0.23% are achieved at 868 MHz. On 42 degrees-LiTaO3, the
      corresponding figures of merit are 1.3 dB for minimum insertion loss and 4.1%
      bandwidth at 1960 MHz. The filters on 42 degrees-LiTaO3 also have remarkably flat
      passbands.

PMID- 17225812
TI  - Modeling of nonlinear responses for reciprocal transducers involving polarization
      switching.
AB  - Nonlinearities and hysteresis effects in a reciprocal PZT transducer are examined
      by use of a dynamical mathematical model on the basis of phase-transition theory.
      In particular, we consider the perovskite piezoelectric ceramic in which the
      polarization process in the material can be modeled by Landau theory for the
      first-order phase transformation, in which each polarization state is associated
      with a minimum of the Landau free-energy function. Nonlinear constitutive laws
      are obtained by using thermodynamical equilibrium conditions, and hysteretic
      behavior of the material can be modeled intrinsically. The time-dependent
      Ginzburg-Landau theory is used in the parameter identification involving
      hysteresis effects. We use the Chebyshev collocation method in the numerical
      simulations. The elastic field is assumed to be coupled linearly with other
      fields, and the nonlinearity is in the E-D coupling. We present numerical results
      for the reciprocal-transducer system and identify the influence of nonlinearities
      on the system dynamics at high and low frequency as well as electrical impedance
      effects due to tuning by a series inductance. It is found that nonlinear effects
      are not important at high frequencies (1 MHz) subject to high-input voltages, but
      they become important under high-voltage and off-resonance conditions.

PMID- 17225813
TI  - An exact analysis of a rectangular plate piezoelectric generator.
AB  - We study thickness-twist vibration of a finite, piezoelectric plate of polarized
      ceramics or 6-mm crystals driven by surface mechanical loads. An exact solution
      from the three-dimensional equations of piezoelectricity is obtained. The plate
      is properly electroded and connected to a circuit such that an electric output is
      generated. The structure analyzed represents a piezoelectric generator for
      converting mechanical energy to electrical energy. Analytical expressions for the
      output voltage, current, power, efficiency, and power density are given. The
      basic behaviors of the generator are shown by numerical results.

PMID- 17225814
TI  - Thermal compensation in GaPO4 beam resonators: experimental evidence for length
      extensional mode.
AB  - Temperature effects in gallium orthophosphate (GaPO4) vibrating beams are
      reported. In addition to the well-known, thickness-shear AT-cut, temperature
      compensated cuts exist in GaPO4 for length extensional modes. Experimental
      evidence of a temperature-compensated cut in GaPO4 rectangular beam resonator
      vibrating in length extension is given.

PMID- 17225815
TI  - An ultrasound research interface for a clinical system.
AB  - Under a contract with the National Cancer Institute, we have developed a research
      interface to an ultrasound system. This ultrasound research interface (URI) is an
      optional feature providing several basic capabilities not normally available on a
      clinical scanner. The URI can store high-quality beamformed radio-frequency data
      to file for off-line processing. Also, through an integrated user interface, the
      user is provided additional control over the B-mode receive aperture and color
      flow ensemble size. A third major capability is the ability to record and
      playback macro files. In this paper, we describe the URI and illustrate its use
      on three research examples: elastography, computed tomography, and spatial
      compounding.

PMID- 17225816
TI  - Sources of dietary fluoride intake in 6-7-year-old English children receiving
      optimally, sub-optimally, and non-fluoridated water.
AB  - OBJECTIVES: Due to increased consumption of pre-packaged drinks, tap water may no
      longer be the principal source of water intake and consequently fluoride intake.
      Little is known about the importance of solid foods as fluoride sources and how
      the relative contribution of foods/drinks to fluoride intake is affected by
      residing in fluoridated or non-fluoridated areas. This study investigated the
      relative contributions of different dietary sources to dietary fluoride intake
      and compared this in children residing in optimally artificially fluoridated, sub
      optimally artificially fluoridated, and non-fluoridated areas. METHODS: Thirty
      three healthy children aged 6 years were recruited from fluoridated and non
      fluoridated communities and categorised into three groups based on fluoride
      content of home tap water: optimally fluoridated (< or =0.7 mgF/L), sub-optimally
      fluoridated (> or =0.3 to < or =0.7 mgF/L) and non-fluoridated (50.3 mgF/L)
      drinking water. A 3-day dietary diary collected dietary information. Samples of
      foods/drinks consumed were collected and analyzed for fluoride content. RESULTS:
      Drinks provided 59%, 55% and 32% of dietary fluoride intake in optimally, sub
      optimally and non-fluoridated areas respectively. Tap water, fruit squashes and
      cordials (extremely sweet non-alcoholic fruit flavoured drink concentrates)
      prepared with tap water, as well as cooked rice, pasta and vegetables were
      important sources of fluoride in optimally and sub-optimally fluoridated areas.
      Carbonated soft drinks and bread were the most important contributors to dietary
      fluoride intake in the non-fluoridated area. CONCLUSION: The main contributory
      sources to dietary fluoride differ between fluoridated and non-fluoridated areas.
      Estimating total fluoride intake from levels of fluoride in tap water alone is
      unlikely to provide a reliable quantitative measure of intake. Studies monitoring
      dietary fluoride exposure should consider intake from all foods and drinks.

PMID- 17225817
TI  - Oral health status of San Francisco public school kindergarteners 2000-2005.
AB  - OBJECTIVES: To determine the prevalence of dental caries and oral health
      disparities in San Francisco kindergarten public school children from 2000-2005.
      METHODS: The San Francisco Department of Public Health in partnership with the
      San Francisco Dental Society and assistance from the National Dental Association,
      has been conducting annual dental screenings of kindergarten children enrolled in
      the San Francisco Unified School District since 2000. Outcomes assessed from this
      series of cross-sectional screenings included prevalence of caries experience,
      untreated caries, treatment needs, and caries severity by child's sex,
      race/ethnicity, residential zip code, and a proxy for socioeconomic status.
      RESULTS: Of 76 eligible schools, 62-72 participated, and 86-92% of enrolled
      children (n=3,354-3,527) were screened yearly. Although there was a small,
      significant decrease over the time period, in 2005, 50.1% of children had caries
      experience; 28.8% had untreated caries and 7.6% had urgent treatment needs. Each
      year caries prevalence was greatest for Asian children, those attending schools
      with > 50% children eligible for the free or reduced-price meal program, and
      children living in zip codes in and around Chinatown and San Francisco's southern
      border. CONCLUSIONS: Despite signs of improvement, caries remains a public health
      problem especially in Asian and Hispanic children, and children living in certain
      sections of San Francisco.

PMID- 17225818
TI  - A comparison of the impact of information from a clinician and research-based
      information on patient treatment choice in dentistry.
AB  - OBJECTIVES: There is an imperative that clinicians should employ an evidence
      based approach to both clinical care and treatment, and involve patients in the
      decision-making process. In Britain, public policy emphasizes the importance of
      patient involvement, participation and partnership in health care, however little
      is known of the effect of evidence-based information on this. This study compares
      treatment decisions made by dental patients on the basis of two sources of
      evidence: clinician and research. METHOD: Vignette method with the two sources of
      evidence as experimental variables. The study population was a convenience sample
      of dental patients recruited from a clinic waiting area at a Dental Hospital
      (n=100). Each participant read a vignette describing a visit to the dentist for
      treatment of severe toothache in a back tooth. The nature and purpose of the
      visit was identical in each vignette. The participants indicated their decision
      about possible treatment, based on the information they had been given in the
      vignette and rated their confidence in the decision on a three point Likert
      scale. Additionally participants' were asked to rate their own oral health.
      RESULTS: Research evidence influences the confidence patients have in their in
      decision especially when it supports clinical judgement and where individuals
      value their oral health. Research evidence does not replace the confidence that
      patients have in the dentist's clinical judgement. CONCLUSION: Dental patients'
      willingness to engage in treatment is influenced by the dentist's clinical
      recommendation and the importance of oral health to the patient.

PMID- 17225819
TI  - Preferences for oral health states in a US community-dwelling functionally
      impaired older adult population: 2000-2001.
AB  - OBJECTIVES: To determine whether and how much time in a state of ill oral health
      an older person would be willing to trade for optimal oral health. METHODS: This
      is a cross-sectional observational study of 76 subjects (52 female, 24 male) ages
      47-93 (mean 75.2) recruited from a Medicare demonstration. Subjects had to need
      or receive help with 2+ activities of daily living (ADLs) or 3+ instrumental ADLs
      plus had to have had recent significant healthcare services use. A Time Trade-Off
      (TTO) approach was used. TTO utility is defined as the amount of symptom-free
      time (i.e., the optimal oral health state) divided by the amount of time with
      symptoms (either their current oral health state or the worst imaginable oral
      health state, depending on the scenario), at the point of indifference (the point
      past which the person is unwilling to trade additional life expectancy). RESULTS:
      When starting from their current oral health state, 39% of the subjects were
      willing to exchange time resulting in a shorter life with optimal oral health.
      They were willing to trade 14.0 months of life on average and valued each year in
      their current oral health state as 91% of a year in optimal oral health. When
      starting in the poorest oral health state, 79% of the subjects were willing to
      accept a shorter life. They were willing to trade 33.7 months of life on average,
      and valued the poorest state as worth 79% of a year in optimal oral health.
      CONCLUSIONS: Dentists should take into consideration this group's preference for
      optimal oral health.

PMID- 17225820
TI  - Deficits in perceptions of oral health relative to general health in populations.
AB  - OBJECTIVE: To compare perceptions of general health versus oral health within two
      populations. METHODS: Secondary analysis of cross-sectional survey data obtained
      from representative samples of dentate adults in Australia and the United States.
      Australian data were collected in the 2002 National Dental Telephone Interview
      Survey and United States data were from the NHANES, 1988-1994. A stratified
      analysis compared self-ratings of general and oral health among groups classified
      by age, socioeconomic status and access to dental care. RESULTS: In Australia,
      43.6% rated their dental health 'very good' or 'excellent' whereas 58.6% rated
      their general health 'very good' or 'excellent'--a deficit of 15.0%. In the US,
      there was a comparable deficit of 24.2%. The deficit could be explained as a
      'generation gap' where oral health ratings of the youngest cohort resembled the
      general health ratings of middle-aged adults in Australia and retirees in the US.
      An 'affluence gap' was evident where the oral health ratings of wealthier adults
      resembled the general health ratings of disadvantaged adults. Among Australians
      with private dental insurance who had visited a dentist in the past year the oral
      health deficit was negligible. Similar stratification in the US sample
      considerably attenuated the deficit. CONCLUSION: There is a deficit in perceived
      oral health compared with general health at all stages of adulthood and spanning
      the socioeconomic spectrum. The deficit was diminished among insured adults who
      had made a dental visit within the preceding year, suggesting that improved
      access to dental services may help redress the discrepancy.

PMID- 17225821
TI  - Can oral health-related quality of life measures substitute for normative needs
      assessments in 11 to 12-year-old children?
AB  - OBJECTIVES: 1) assess the relationship between a measure of condition-specific
      oral health-related quality of life (OHRQoL) and the related normative need for
      dental treatments, and 2) test the diagnostic validity of the condition-specific
      OHRQoL measure for specific dental conditions in a group of primary school
      children. METHODS: A cross-sectional study of all 11 to 12 year-olds carried out
      in a municipal area of Suphanburi province, Thailand. 1034 children (91.8%) were
      dentally examined to assess their normative needs for 6 types of treatment
      (dental caries, traumatic dental injuries, enamel defects, periodontal,
      orthodontic and prosthodontic treatment). OHRQoL was assessed using the Child
      OIDP index and its Condition-Specific impacts measure for the 6 treatment types.
      RESULTS: The prevalence of specific types of normative needs ranged from 3.2%
      (prosthodontic) to 97.0% (periodontal) and for Condition-Specific oral impacts
      from 0.7% (prosthodontic) to 50.6% (dental caries). Despite their statistically
      significant relationship for every treatment type except for periodontal
      treatment when need was indicated by a CPI score of 1, there were large
      differences between measures of normative need and oral impacts. High proportions
      of children had normative need without impacts and vice versa. The biggest
      differences were for appearance-related conditions (e.g. enamel defects and
      orthodontic treatment). For every type of treatment, oral impacts poorly
      predicted the normative needs of individuals. CONCLUSIONS: Although normative
      needs and OHRQoL are associated, when assessed appropriately, there was
      considerable discrepancy between them. OHRQoL measures cannot replace normative
      needs. Instead, both should be used in combination in order to cover different
      dimensions of oral health.

PMID- 17225822
TI  - School performance indicators as proxy measures of school dental treatment needs:
      a feasibility study.
AB  - OBJECTIVE: This ecological study assessed the feasibility and predictive ability
      of readily available educational indicators as proxy measures of school dental
      treatment needs in York Region elementary school children, Canada. METHOD: Data
      sources included York Region Dental Health Unit dental screening data (2003
      2004); area-based income data from Statistics Canada (2001) based on school
      address postcodes; grade three and grade six school performance results in
      reading, writing mathematics and English as a second language (ESL) data (2003
      2004) obtained from publicly accessible educational websites. RESULTS: Data
      analyses included 219 schools. Pearson's correlations showed that schools with a
      higher percentage of children needing urgent dental treatment had significantly
      higher proportions of children scoring below provincial averages in all six
      school performance categories. Hierarchical stepwise multiple linear regression
      analysis showed that two school performance variables remained in the model after
      controlling for area-based median family income and ESL variables: the percentage
      of grade six pupils scoring below the provincial average in writing and the
      percentage of grade 3 pupils scoring below the provincial average in reading.
      CONCLUSIONS: The study established the feasibility of using school-level school
      performance indicators as proxy measures of school-level dental treatment needs.
      School performance results were good predictors of urgent dental treatment in
      York Region elementary school children. Further studies are needed using data
      from other jurisdictions to determine the utility of educational indicators in
      oral health programs.

PMID- 17225823
TI  - Linguistic adaptation and validation of the General Oral Health Assessment Index
      (GOHAI) in an elderly Japanese population.
AB  - OBJECTIVES: This study sought to develop a Japanese version of the General Oral
      Health Assessment Index (GOHAI) and validate its use in an elderly Japanese
      population. METHODS: The GOHAI scale was translated in a standardized way
      consisting of forward translation, pilot study, and backward translation.
      Psychometric properties of the final version were assessed on 175 participants
      (mean age: 70.0 years, SD 6.4). RESULTS: The response rate was more than 98% for
      each item. The reliability in terms of a Cronbach's alpha value was 0.89. The
      mean GOHAI scores were significantly lower for participants with poor perceived
      oral health (P<0. 001) or poor perceived general health (P<0.01). Significant
      correlations were observed between the GOHAI scores and the general health or
      physical functioning scores of the Medical Outcome Study Short Form 36 (P<0.01).
      CONCLUSIONS: The present study showed that the Japanese version of the GOHAI was
      psychometrically valid in an elderly sample population.

PMID- 17225824
TI  - Oral health, related behaviors and oral health impacts among homeless adults.
AB  - OBJECTIVE: To assess the oral health needs, related behavior and oral health
      impact among homeless persons in Newark, New Jersey. METHODS: Participants
      represented a convenience sample of adults (n=46) participating in Homeless
      Services Day, an annual event sponsored by the Homeless Services Division of the
      Newark, NJ Department of Health and Human Services. Their mean age was 40.4 yr
      (SD=10.0), and 51.1% were female. The majority (76%) reported African-American
      ethnicity; remaining participants self-identified as Hispanic, White or Asian.
      Participants reported being homeless for a median of 11 months, with a range of 1
      to 108 months. RESULTS: The 46 participants had 745 teeth (averaged 16.2 per
      person) that were either missing, had fillings or had untreated decay. Diseased
      teeth averaged 3.8 per person; missing teeth averaged 8.6 per person; and filled
      teeth averaged 3.7 per person. Only 28.3% had a dental visit in the past year.
      Approximately 87% reported negative oral health impacts impact: over half (55.6%)
      had current oral facial pain and two-thirds of our participants reported having
      dental-related face pain during the past year. Additional oral health impacts
      included: eating (42%), smiling (33%), concentrating (18%) and talking (16%).
      CONCLUSIONS: Consistent with other studies, this homeless sample presented with
      considerable oral health needs. Newark's homeless, like other homeless cohorts,
      face access to care and negative oral health impacts. This study informs the need
      for future research that can provide substantive evidence for care providers and
      policy makers.

PMID- 17225825
TI  - Association of smoking in household and dental caries in Japan.
AB  - OBJECTIVES: The study investigated the relationship between smoking in the
      household and dental caries in Japanese children using nationally representative
      cross-sectional data. METHODS: This study included 925 children aged 1-14 years.
      A child was considered to have decayed and/or filled teeth if a dentist diagnosed
      these conditions in deciduous or permanent teeth. Smoking in the household was
      defined as positive if someone in the household reported smoking cigarettes.
      RESULTS: No statistically significant relationship was observed between household
      smoking and caries experience. However, smoking in the household was
      independently associated with an increased prevalence of decayed teeth. The
      adjusted mean of filled teeth among children exposed to household smoking was
      higher than that among non-exposed children. CONCLUSIONS: The results of the
      study failed to substantiate a positive association between passive smoking and
      caries experience in Japanese children.

PMID- 17225826
TI  - Infection control measures among senior dental students in Rio de Janeiro State,
      Brazil.
AB  - OBJECTIVE: The aim of this study was to verify the practices and attitudes of
      senior dental students about infection control procedures. METHODS: A cross
      sectional survey was performed during the 1st semester of 2003. Open- and close
      ended questions were given to 196 students in 6 universities. RESULTS: Overall,
      90.8% of students had been vaccinated for hepatitis B. Only 25.0% have been
      assessed for anti-HBs. A total of 99.5% students reported always using gloves for
      all procedures. Eye protection were always used by 84.2% of students, and all the
      students used face masks for all procedures. Caps or hair covers were used by
      92.3% of students and 87.8% reported no objection to treating patients with
      infectious diseases. Among instructors, the students observed that 60.2% of them
      did not use gloves for all procedures, 43.4% of those didn't change gloves
      between patients. CONCLUSIONS: These results address the need for an improved
      quality assurance, in order for the students and faculty to improve their
      practices and attitudes on infection control measures.

PMID- 17225827
TI  - Specific caries index: A new system for describing untreated dental caries
      experience in developing countries.
AB  - OBJECTIVES: To develop a reproducible surface-specific caries index that provided
      qualitative and quantitative information about untreated dental caries, that
      could be used in conjunction with the DMFS index and would provide information on
      not only the caries prevalence but also the location and type of caries lesion in
      an individual based on clinical examination. METHODS: Untreated carious lesions
      were divided into six types based on the location of the lesions. 339 rural
      school children in the age group of 12-15 years were examined for dental caries
      using both the DMFS index and the Specific Caries Index. RESULTS: Type 1 and 2
      were found to be the most common type of caries lesions. The reproducibility of
      the Specific Caries Index was also found to be good. CONCLUSIONS: Encouraging
      indications about the validity and reproducibility of this new caries index was
      found, suggesting the need for further studies to test its applicability in
      larger and different populations.

PMID- 17225828
TI  - Dental health differences by social class in home-dwelling seniors of Barcelona,
      Spain.
AB  - BACKGROUND: The aim of this study was to assess dental health differences by
      social class in home-dwelling seniors in Spain. METHODS: A cross-sectional
      household survey of a cohort of senior residents in Barcelona (Spain) was
      undertaken. Of 891 survivors (72 years or older), 561 (62.9%) oral examinations
      were completed according to the DMF Index (Decayed, Missing and Filled teeth).
      RESULTS: 42% of participants were edentate. The individuals of social class IV-V
      were more likely to be edentate, and to have fewer than 15 teeth compared to
      those in social class I-II. The DMF Index in dentate individuals (Adjusted
      mean=16.4) also showed significantly worse dental health for lower social classes
      (p = 0.001). CONCLUSIONS: The results of this study indicate a different level of
      utilization of dental health services and dental health by social class in home
      dwelling seniors. Further research is needed to understand the barriers of access
      and social inequality.

PMID- 17225829
TI  - Childhood overweight and orthodontists: results of a survey.
AB  - OBJECTIVES: A survey among orthodontists to assess clinical procedures of
      overweight screening and nutrition intervention among youth was conducted.
      METHODS: Orthodontists identified through professional society membership were
      invited to participate via email. The web-based survey collected information
      regarding overweight screening, nutrition counseling, and referral habits.
      RESULTS: 91% of 111 respondents reported counseling children and families on
      nutrition recommendations. Referral of overweight youth to a dietitian or
      pediatrician was sporadic. Orthodontists who felt that overweight had a severe
      negative impact on dental health were more likely to screen patients for
      overweight and perform dietary counseling for all patients than orthodontists who
      felt the impact of overweight on dental health was less severe. CONCLUSIONS:
      Orthodontists report regularly engaging in dietary discussions with their
      pediatric patients and may serve as important clinical advocates for healthy
      dietary choices among youth. Overweight screening and referral practices among
      orthodontists to appropriate health professionals should be further evaluated as
      interventions for pediatric obesity.

PMID- 17225830
TI  - Periodontal status as predictor of prematurity and low birth weight.
AB  - OBJECTIVE: The objective was to verify the relation between periodontal status
      and prematurity/low birth weight. METHODS: a case control study of 211 women, 44
      being mothers of children born with weight below 2.500g or gestational age of
      less than 37 weeks (case group) and 177 mothers of children born with weight of
      over 2.500g or more and gestational age of 37 weeks or more (control group). The
      women were invited to reply to a questionnaire during the interview. A single
      dentist performed a complete periodontal exam in the oral cavity of each
      participant, including: probing depth, recession, plaque index, bleeding on
      probing, and clinical attachment loss measurements. Descriptive analysis of the
      study variables was performed and the statistical significance was calculated at
      5%, using the chi-squared test. RESULTS: There was no statistically significant
      difference in the clinical parameters between the groups. CONCLUSIONS: The
      findings showed no association between periodontal status and prematurity/low
      birth weight.

PMID- 17225831
TI  - Challenges in making therapeutic lifestyle changes among hypercholesterolemic
      African-American patients and their physicians.
AB  - OBJECTIVE: We explored challenges faced by hypercholesterolemic African-American
      primary care patients and their physicians regarding therapeutic lifestyle
      changes (TLC) and provide patient-influenced recommendations to physicians.
      METHODS: In this qualitative study, 23 urban family medicine patients and their
      physicians (N=12) participated in separate focus groups, where they were asked
      semistructured, open-ended questions about knowledge and barriers to lifestyle
      treatment of high cholesterol. RESULTS: During the focus groups, barriers
      mentioned by physicians were: lack of time for TLC counseling, inadequate
      knowledge about counseling patients, and patient readiness and responsibility to
      change. Patient-revealed barriers included difficulty adhering to a diet/exercise
      regimen and a lack of knowledge about high cholesterol. Patients who were
      successful with adopting a healthy lifestyle identified personal experiences or
      those of family and friends as motivating. CONCLUSION: Physicians desire training
      and resources to better help patients adopt diet and exercise regimens specific
      to their general and health literacy and their access to healthy foods, along
      with their readiness to change. Patients desire that physicians tailor their TLC
      advice to be specific to their context and they want help from physicians in
      setting realistic goals. Such a patient-centered counseling approach may improve
      adherence to lifestyle guidelines and, thus, clinical outcomes.

PMID- 17225832
TI  - Toward eliminating health disparities in HIV/AIDS: the importance of the minority
      investigator in addressing scientific gaps in Black and Latino communities.
AB  - Dialogue in the medical and public health communities has increasingly focused
      attention in the area of health disparities. We believe that the elimination of
      health disparities in the United States will require a multipronged approach that
      includes, at the very least, new approaches in both biomedical and prevention
      interventions. We also believe that since health disparities primarily affect
      communities of color, a model which fosters the development of junior scientists,
      clinicians and researchers of color who serve these communities will yield
      important progress in this field. The Minority HIV/AIDS Research Initiative at
      the Centers for Disease Control and Prevention (CDC) is a program that, through
      targeted research, aims to address health disparities in HIV/AIDS. Although the
      program is disease specific, there are a variety of lessons learned from its
      inception and implementation that can be useful throughout the scientific,
      medical and public health communities.

PMID- 17225833
TI  - Acceptance of HIV testing among African-American college students at a
      historically black university in the south.
AB  - PURPOSE: Routine HIV testing on college campuses has the potential to increase
      students' awareness of their HIV status. Testing targeted only at persons
      reporting HIV risk behaviors will not identify infected persons who may deny or
      be unaware of their risk. Thus, this study sought to investigate the
      acceptability of rapid HIV testing among African-American college students in a
      nontraditional setting on a historically black college/university (HBCU) campus.
      METHODS: A cross-sectional survey on risk behaviors, barriers to testing, and HIV
      testing history was administered to 161 African-American college students at an
      HBCU. All approached students (both those participating and not) were offered
      free HIV rapid testing. RESULTS: Eighty-one African-American college students
      consented to be tested for HIV and all tested negative. Results of the
      questionnaire indicated that African-American college students engage in risky
      sexual behaviors (such as unprotected sex) yet perceive themselves as at little
      or no risk. College students who reported past HIV testing often did so in
      conjunction with routine exams, such as annual pap smears, rather than
      specifically seeking HIV testing. CONCLUSIONS: Routine HIV testing on college
      campuses may be an important public health initiative in reducing the spread of
      HIV. Specifically, this strategy may provide a model for student access to HIV
      testing, particularly males and other students who may be less likely to seek HIV
      testing at traditional medical settings. These data supports expansion of routine
      testing programs directed at African-American college students.

PMID- 17225834
TI  - Knowledge of HIV/AIDS and attitude towards voluntary counseling and testing among
      adults.
AB  - BACKGROUND: Nigeria has the third highest population of people living with human
      immunodeficiency virus (HIV). Despite this, the knowledge of HIV/AIDS and uptake
      of voluntary counseling and testing (VCT) is still low, especially in the rural
      areas. This study assessed knowledge of HIV/AIDS and attitude towards VCT among
      adults in a rural community in northern Nigeria. METHODS: A pretested
      questionnaire was administered on a cross-section of 210 adults in Danbare
      village, northern Nigeria. Information about knowledge of HIV/AIDS and attitudes
      toward VCT was elicited among respondents. RESULTS: The majority of respondents
      (59%) did not know the causative agent of AIDS; however, knowledge of route of
      disease transmission was high, with 71% and 64% of study participants mentioning
      sexual activity and unscreened blood transfusion, respectively, as possible
      transmission routes. Respondents listed avoidance of premarital sex, outlawing
      prostitution, condom use and screening of blood before transfusion as protective
      measures. Overall, 58 (27.6%), 80 (38.1%) and 72 (34.3%) of the respondents had
      good, fair and poor knowledge of HIV/AIDS, respectively. After adjusting for
      confounders, female gender and formal education remained significant predictors
      of HIV/AIDS knowledge. Reasons for rejection of VCT included fear of stigma,
      marital disharmony, incurable nature of the disease and cost of treatment. Formal
      education, female gender and HIV knowledge significantly predicted positive
      attitude toward VCT for HIV/AIDS among the study population. CONCLUSION: More
      than half of the respondents had adequate knowledge of HIV/AIDS, and the majority
      were willing to have VCT. However, misconceptions, fear, gaps in knowledge and
      limited access to VCT remain prevalent. Our findings suggest the need to provide
      health education and scale up VCT services in northern Nigeria by targeting the
      efforts of international and local development partners to underserved rural
      areas.

PMID- 17225835
TI  - Sexual history-taking among primary care physicians.
AB  - BACKGROUND: Because many people seek sexual healthcare in settings where they
      seek primary healthcare, the extent to which primary care physicians take sexual
      histories is important. We surveyed Atlanta-area primary care physicians to
      estimate the extent to which they take sexual histories as well as the components
      of those histories and the circumstances under which they are taken. METHODS:
      Four-hundred-sixteen physicians in four specialties (obstetrics/gynecology,
      internal medicine, general/family practice, pediatrics) responded to a mail
      survey conducted during 2003-2004. Respondents answered whether they asked about
      sexual activity at all, including specific components of a comprehensive sexual
      history such as sexual as sexual orientation, numbers of partners and types of
      sexual activity, during routine exams, initial exams, complaint-based visits or
      never. Respondents also reported their opinions on whether they felt trained and
      comfortable taking sexual histories. RESULTS: Respondents (51% male, 58% white)
      saw an average of 94 patients per week. A majority (56%) felt adequately trained,
      while 79% felt comfortable taking sexual histories. Almost three in five (58%)
      asked about sexual activity at a routine visit, but much smaller proportions (12
      34%) asked about the components of a sexual history. However, 76% of physicians
      reported asking about sexual history (61-75% for various components) if they felt
      it would be relevant to the chief complaint. CONCLUSIONS: Most physicians report
      feeling comfortable taking sexual histories and will do so if the patient's
      apparent complaint is related to sexual health. But sexual histories as part of
      routine and preventive healthcare are less common, and many physicians miss
      essential components of a comprehensive sexual history. Structural changes and
      suggestions for training to enhance sexual history-taking are discussed.

PMID- 17225836
TI  - Racial and ethnic disparities in cancers of the uterine corpus.
AB  - Survival after diagnosis of cancer of the uterine corpus is significantly worse
      in black women as compared with white women. The etiology of the racial and
      ethnic disparities that exist in endometrial cancer incidence and outcome is
      multifactorial and complex. Potential explanations include cancer biology,
      differences in access to care, sociodemographic characteristics, response to
      treatment and comorbid factors. In this article, a review was performed to assess
      the magnitude and reasons for the observed disparity in endometrial cancer
      mortality. Strategies and recommendations to reduce or eliminate differences in
      endometrial cancer outcome are explored. These include advocacy for more research
      to clarify the underlying causes of cancer disparities at all levels, including
      the molecular basis of disparate outcomes, improving access to quality healthcare
      services, establishing culturally competent models of healthcare delivery, and
      developing novel cost-effective screening and early prevention methods.

PMID- 17225838
TI  - Epidemiology of trauma deaths in an urban level-1 trauma center predominantly
      among African Americans--implications for prevention.
AB  - This is a retrospective review to determine demographics, presentation and injury
      characteristics of trauma deaths at Howard University Hospital over an 1-year
      period (1994-2005) and to make recommendations for education and prevention in
      the community based on our findings. Data was obtained from the Howard University
      Hospital trauma registry. From the study period 1994-2005, there was a total of
      365 trauma deaths. The injuries sustained were mainly intentional, which
      accounted for almost 75% of cases--the majority of deaths being due to
      penetrating injuries. There was an almost two-fold increase in trauma deaths on
      Saturdays compared to the rest of the week. The demographics of our study
      population were similar to those reported in the trauma literature. These were
      younger patients and predominantly male. Unique to our population was the
      overwhelming predominance of African-American patients (90%). With these unique
      features, injury prevention would be better served focusing on social and
      community prevention and education rather than the usual methods of blunt-trauma
      prevention--e.g., pedestrian- and motor-vehicle-oriented policies, which may be
      more beneficial in other trauma systems.

PMID- 17225837
TI  - Racial disparity in primary hepatocellular carcinoma: tumor stage at
      presentation, surgical treatment and survival.
AB  - OBJECTIVES: The incidence and mortality rates from primary hepatocellular
      carcinoma (HCC) are higher in black Americans compared to whites. The goal of
      this study was to determine if there are racial disparities in HCC stage at
      diagnosis and treatment. METHODS: We compared patient age, tumor stage, rates of
      surgical intervention and survival in black (n=1718) and white (n=9752) HCC cases
      between 1992 and 2001 in the Surveillance, Epidemiology and End Results (SEER)-11
      + Alaska database. RESULTS: Black HCC cases were significantly younger at
      diagnosis (p < 0.0001). Black cases were more likely to have regional and distant
      metastasis at presentation (p < 0.0005) and were less likely to have surgery
      performed (p < 0.001). The racial difference in surgery treatment was significant
      among patients with localized (p = 0.001) and regional (p = 0.012) HCC, but not
      with distant HCC. Overall survival rates were lower in blacks (p = 0.0033).
      Survival was similar in blacks and whites with regional and distant disease. Yet,
      among patients with localized HCC, survival rates were lower in blacks (p =
      0.0030). CONCLUSIONS: Black HCC patients have more advanced tumor stage at
      diagnosis and lower rates of both surgical intervention and survival. The racial
      disparities in surgical treatment utilization and survival were most striking
      between black and white HCC patients with localized HCC.

PMID- 17225839
TI  - Experience with surgical internal drainage of pancreatic pseudocyst.
AB  - BACKGROUND: Pancreatic pseudocyst is an uncommon disorder in Nigeria compared
      with the Caucasian population. OBJECTIVE: This study was carried out to determine
      the pattern and outcome of surgical management of the disease in a Nigerian
      population. METHODS: The authors reviewed the records of 10 consecutive patients
      with pancreatic pseudocysts who were surgically managed in Aminu Kano Teaching
      Hospital, Kano, Nigeria, from November 1998 to October 2005. RESULTS: There were
      four males and six females, with a mean age of 19.2 years. The etiological
      factors included idiopathic acute pancreatitis in a two-year old child and blunt
      abdominal trauma in two patients. In seven patients, the cause could not be
      determined. The most common clinical features included epigastric pain, fever,
      intra-abdominal mass and vomiting. The duration of symptoms ranged from 15-204
      days (mean=102 days). Open cystogastrostomy was done in eight patients, and two
      patients had cystoduodenostomy. The mean duration of hospital stay after surgery
      was 9.4 days (range = 7-15 days). There was no recurrence in any of the patients
      after about 3-9 months of follow-up with ultrasonography, and no death was
      recorded. CONCLUSION: Open surgical internal drainage is safe and effective with
      low morbidity and mortality. There is a need for provision of facilities for
      minimally invasive laparoscopic and endoscopic techniques.

PMID- 17225840
TI  - Antibody level after hepatitis-B vaccination in hemodialysis patients: impact of
      dialysis adequacy, chronic inflammation, local endemicity and nutritional status.
AB  - We prospectively studied the evolution of HBsAg antibody (HBsAb) after primary
      vaccination (four doses; Engerix B, 40 pg i.m at 0, one, two and six months) in
      29 patients who were seronegative (HBsAb <10 IU/L), had not been previously
      vaccinated and were on hemodialysis. Their mean age was 45.58 +/- 10.98 years,
      and the hemodialysis duration ranged from 1-21 years. In addition, we assessed
      dialysis adequacy for all cases on four different occasions beside the estimation
      of predialysis serum albumin, serum ferritin, C-reactive protein (CRP),
      transferrin saturation ratio (TSAT), body mass index (BMI) and subjective global
      assessment (SGA). We measured anti-HBs titer eight weeks after the fourth dose.
      Our results showed that two patients (6.90%) were nonresponders (HBsAb <10 IU/L)
      after the completion of vaccination. One patient (3.45%) was a weak responder (10
      100 IU/L). Strikingly, 26 patients (89.65%) showed good antibody response (>100
      IU/L). HBsAb titers showed no significant correlation with age, duration of HD
      therapy, serum albumin, CRP, TSAT level, BMI or SGA scores (p > 0.05). Responders
      to primary vaccination had significantly higher levels of urea reduction ratio
      (%) and Kt/V compared to nonresponders (63.61 +/- 6.97% and 1.25 +/- 0.15 vs.
      52.0 +/- 2.10% and 0.92 +/- 0.13, respectively, P < 0.05). In conclusion, this
      was a preliminary study showing a very high response to hepatitis-B vaccination
      among hemodialysis patients that neither correlated with age, systemic
      inflammation nor nutritional status. Efficient hemodialysis was associated with
      good response to hepatitis-B vaccine.

PMID- 17225841
TI  - Review of data of the patients receiving total parenteral nutrition at the
      intensive care unit of a university hospital.
AB  - Parenteral nutrition is commonly administered to patients in intensive care units
      who cannot be fed gastrointestinally. Several problems might be encountered
      during parenteral nutrition. We designed this study to evaluate two years' data
      of the patients who received parenteral nutrition at the intensive care unit of
      the university hospital. Forty-five patients who were treated at this hospital
      between January 1, 2004 and December 31, 2005 were included in this study.
      Patient data were collected via questionnaires designed based on the information
      in the literature. Blood, urinary, oropharyngeal and catheter entry site cultures
      were obtained and analyzed on the third and seventh days of the treatment. We
      found the following results: 31.1% of the patients received parenteral nutrition
      due to renal insufficiency; ready-made amino acid/lipid solutions were used in
      86.7% of the patients; 77.8% of the solutions were administered through a
      peripheral vein; 88.6% of total parenteral nutrition solutions given thorough the
      peripheral vein had higher osmolarities than 800 mOsmol/L; routine Fe and Fe
      binding capacity, prothrombin time, cholesterol and triglyceride level
      assessments were not performed before the initiation of treatment; and the
      culture tests most commonly revealed Staphylococcus epidermidis in the blood,
      Candido species in urine, Streptococcus in throat, and Staphylococcus aureus at
      catheter entry sites. Based on these results, we suggest that organizing a
      nutrition support team would be useful in order to improve the quality of the
      nursery and to provide close and rational management and follow-up of the
      patients receiving total parenteral nutrition.

PMID- 17225842
TI  - Route of nutrition has no effect on the development of infectious complications.
AB  - BACKGROUND: Infection is a serious complication of nutritional support, causing a
      high rate of mortality and morbidity. Critically ill patients having nutritional
      support are prone to infectious complications. Questions regarding the effects of
      the route of nutrition in infectious complications have been asked. We aimed to
      determine the relationship between the route of nutrition and the risk of
      developing infectious complications in severely ill patients on nutritional
      support in an intensive care unit. METHODS: A retrospective review was performed
      on the files of 144 severely ill patients who had either enteral or parenteral
      nutrition during follow-up in an intensive care unit. The primary diagnoses of
      patients were heterogenous. RESULTS: Sixty-eight (35.8%) of them acquired novel
      infections during the hospitalization period. Forty-nine and 19 of the 68
      infected patients had enteral and parenteral nutrition support, respectively.
      Seventy-six (40%) of the patients were free of infection. Fifty-one of 76
      infection-free patients had enteral nutrition support, and 25 of them had
      parenteral nutrition support. Pulmonary infections, urinary tract infections,
      catheter infections and septicemia were the most frequent types of infectious
      complications. There was no significant difference in the rate of infectious
      complications between enteral nutrition and parenteral nutrition groups (p >
      0.05). CONCLUSION: We conclude that the route of the nutritional support in
      severely ill patients having nutritional support in an intensive care unit does
      not affect the rate of infectious complications. We think that comorbid medical
      conditions and the need of intensive care unit support are more important
      parameters that determine the risk of development of infectious complications.

PMID- 17225843
TI  - The epidemiology of pulmonary embolism: racial contrasts in incidence and in
      hospital case fatality.
AB  - Mortality from pulmonary embolism (PE) has declined in the United States over the
      past two decades, yet significant racia l disparities persist with the age
      adjusted rates for blacks about twice those for whites. Incidence studies to date
      have not been successful in defining reasons for this disparity, primarily
      because they have not enrolled sufficient numbers of blacks to allow for racial
      comparisons. This study overcomes that limitation by using New Jersey hospital
      discharge data as a surrogate measure for PE incidence. It examines whether
      differences in access to care, in-hospital case fatality, discharge planning or
      other factors might help explain the observed patterns. Our results revealed an
      elevation in the incidence of PE among blacks compared with whites, similar to
      the contrasts in mortality. In-hospital case fatality did not differ notably
      between blacks and whites, indicating that treatment in-hospital is an unlikely
      contributing factor. We found differences in hospital discharge planning and
      insurance status, suggesting that these factors may play a role. Our results
      point to the need for longitudinal studies on the natural history of the disease
      to better identify and hopefully modify the risk factors responsible for the
      persistent disparity in mortality from PE.

PMID- 17225844
TI  - Assessment of cardiac function and rheumatic heart disease in children with
      adenotonsillar hypertrophy.
AB  - Our aim was to evaluate whether adenotonsillar hypertrophy (ATH) is associated
      with rheumatic heart disease (RHD) in children. Fifty-three patients with ATH and
      50 healthy children as a control group were enrolled in the study. Medical
      history and clinical findings were investigated, and echocardiographies were done
      by researchers who were unaware of the diagnosis. The two groups were compared.
      Valvular findings suggesting RHD were encountered in four patients (7.5%) in the
      ATH group and in two children (4%) in the control group. This difference was not
      statistically significant (p = 0.098); however, we found physiological mitral
      regurgitation to be significantly more frequent in the ATH group than in the
      control group (p = 0.023). ATH did not increase the risk of valvulitis related to
      RHD regardless of adenoid size and frequency of the infection. To preclude the
      misdiagnosis of mitral regurgitation that results from RHD, diagnostic criteria
      for pathological mitral regurgitation should be carefully applied.

PMID- 17225845
TI  - Childhood nephrotic syndrome: change in pattern and response to steroids.
AB  - BACKGROUND: In our center, childhood nephrotic syndrome (NS) had been reported
      for over a decade to be steroid sensitive contrary to reports in other parts of
      Nigeria. The purpose of this study was to determine if there are changes in
      presentation and response to steroids, with reviews of the literature on NS.
      METHODS: Analysis of 28 patients seen at the University of Port Harcourt Teaching
      Hospital, Nigeria, from 1999-2004 with the diagnosis of NS was performed.
      RESULTS: There were 14 girls and 14 boys with NS. The peak age was 1-4 years.
      Twenty (71.4%) children had idiopathic nephrotic syndrome (INS). Four had chronic
      renal failure, one had sickle cell disease (HbSS), two were positive to human
      immunodeficiency virus (HIV) 1 and 2, and one had pulmonary tuberculosis. Anemia
      was found in 13 patients, while 17 had Plasmodium falciparum. Plasmodium malariae
      and hepatitis-B surface antigen were not isolated. Renal biopsy was performed in
      four patients and revealed minimal-change disease in one child, focal segmental
      glomerulosclerosis in two and no conclusive result in one patient. Oral
      prednisolone was used in INS. After one month of therapy, 16 of 20 responded, of
      which 12 (75%) were <5 years. The NS relapsed in 15 of 16 steroid-sensitive
      patients. Cyclophosphamide and levamisole were used in four and one patients with
      FRNS, respectively. Four (14.3%) patients died; all were secondary NS.
      CONCLUSION: INS remains common in our center, and the majority respond to steroid
      therapy

PMID- 17225846
TI  - Nanotechnology and nanomedicine: a primer.
AB  - Nanosciences and nanotechnology are transforming a wide array of products and
      services that have the potential to enhance the practice of medicine and improve
      public health. But there are a number of health, safety and environmental issues
      to be addressed. This review summarizes some basic facts about nanotechnology and
      cites examples of its application to medicine and public health.

PMID- 17225847
TI  - Two unusual cases with Wilson's disease: hepatoma and fulminant hepatitis treated
      with plasma exchange.
AB  - We report two atypical cases of Wilson's disease. The first case is a 22-year-old
      male patient with a history of disease for 15 years and diagnosed as Wilson's
      disease upon investigations. Alpha-fetoprotein level was found elevated and
      computed tomography showed a 3.5-cm liver mass. Hepatocellular carcinoma was
      diagnosed. Radiofrequency ablation and liver transplantation were performed
      successfully. The second case is a 24-year-old female patient who presented with
      fulminant hepatitis. Urinary copper excretion and ceruloplasmin levels were
      suggestive of Wilson's disease. Despite chelation therapy, no improvement was
      observed. Plasma exchange therapy was performed for seven days. Her clinical
      status improved, and transplantation was no longer needed. To conclude, although
      hepatoma is rarely seen in Wilson's disease, patients should be examined
      regularly to diagnose it in a treatable stage. Removal of copper and toxic
      metabolites with plasma exchange therapy may be a way of treatment for fulminant
      hepatitis associated with Wilson's disease.

PMID- 17225848
TI  - A malignant itch.
AB  - We report an unusual presentation of a previously healthy three-year-old Chinese
      girl with a four-week history of apparently unexplained generalized intense itch.
      She had no past history of atopy or xerosis. Despite the severe itch, she had
      only minimal scratch marks on her right gluteal region but no flexural
      involvement. The girl was treated as having scabies and eczema and with oral
      antihistamines by various dermatologists without much improvement. She
      subsequently presented to a regional hospital with right hip pain and fever.
      Radiological and histopathological investigations confirmed that she had a
      peripheral T-cell lymphoma. The itch pattern prior to and following chemotherapy,
      as documented by the DigiTrac wrist-held movement monitor, showed a dramatic
      reduction of her nocturnal itch. The pattern was also very different from that of
      atopic dermatitis in that the scratching was of much higher intensity but lower
      frequency. Intractable pruritus associated with a peripheral T-cell lymphoma has
      not been previously reported in the pediatric literature. This report serves to
      alert clinicians of the gold paradigm that in a patient with an unexplained
      generalized itch, lymphoma and other malignancies must be considered.

PMID- 17225849
TI  - A unique case of pulmonary artery leiomyosarcoma.
AB  - Primary pulmonary artery leiomyosarcomas are rare, and the diagnosis is usually
      confused with other, more common, diseases, especially pulmonary embolism. A 52
      year-old male, previously healthy, sustained a cardiac arrest. Chest CT
      angiography diagnosed a "saddle embolus". Local thrombolysis was tried without
      any obvious success. At this point, the possibility of neoplasm was entertained.
      A cardiac MRI showed a nonhomogeneous mass in the proximal pulmonary artery.
      Successful surgery was performed, and histological examination of the resected
      mass was consistent with leiomyosarcoma. A follow-up cardiac MRI showed no
      residual mass. The dilemma associated with diagnosing pulmonary artery
      leiomyosarcomas will be discussed.

PMID- 17225851
TI  - Penile and oral angioedema associated with peanut ingestion.
AB  - Angioedema is characterized by transient, episodic, nonpruritic, nonpitting and
      well-defined edema that involves the subcutaneous or submucosal tissue, and most
      commonly develops in the head and neck region. Angioedema is caused by
      extravasation of plasma into the interstitial space of the affected tissue. We
      describe a six-year-old boy who developed oral and penile angioedema subsequent
      to the ingestion of peanuts.

PMID- 17225850
TI  - Occupational arsine gas exposure.
AB  - Arsine gas exposure is a rare occupational event and can be completely prevented
      with the use of appropriate protective gear. Exposure often occurs when arsine
      gas is generated while arsenic-containing crude ores or metals are treated with
      acid. Cases of toxicity require an index of suspicion and a good history. In
      particular, it should be in the differential diagnosis in patients who present
      acutely with red/bronze skin and hemoglobinuria. Treatment is supportive and may
      include transfusions and dialysis in severe cases. Clinical severity is
      proportionate to the level of exposure, and severity is directly related to the
      onset of symptoms.

PMID- 17225852
TI  - The futility of universal pre-employment chest radiographs.
AB  - In a developmental center, a preemployment chest x-ray was required for all job
      applicants. We scrutinized the pros and cons of this practice through a review of
      the medical literature and our experience, and discussion with our colleagues. We
      concluded that such chest x-ray caused unwarranted radiation exposure, did not
      produce compliance with the tuberculosis laws, gave a false sense of security
      regarding workers' compensation risk management, was contrary to established
      occupational medicine practice guidelines, and was unnecessary and wasteful. We
      discontinued such chest x-rays. The purpose of the pre-employment examination
      should remain narrowly job related. Even long-established procedures require
      periodic utilization review.

PMID- 17225855
TI  - The origins of concentric demyelination: self-organization in the human brain.
AB  - Balo's concentric sclerosis is a rare atypical form of multiple sclerosis
      characterized by striking concentric demyelination patterns. We propose a robust
      mathematical model for Balo's sclerosis, sharing common molecular and cellular
      mechanisms with multiple sclerosis. A reconsideration of the analogies between
      Balo's sclerosis and the Liesegang periodic precipitation phenomenon led us to
      propose a chemotactic cellular model for this disease. Rings of demyelination
      appear as a result of self-organization processes, and closely mimic Balo
      lesions. According to our results, homogeneous and concentric demyelinations may
      be two different macroscopic outcomes of a single fundamental immune disorder.
      Furthermore, in chemotactic models, cellular aggressivity appears to play a
      central role in pattern formation.

PMID- 17225854
TI  - Recognition, perceptions and treatment practices for severe malaria in rural
      Tanzania: implications for accessing rectal artesunate as a pre-referral.
AB  - OBJECTIVES: Preparatory to a community trial investigating how best to deliver
      rectal artesunate as pre-referral treatment for severe malaria; local
      understanding, perceptions of signs/symptoms of severe malaria and treatment
      seeking patterns for and barriers to seeking biomedical treatment were
      investigated. METHODOLOGY/PRINCIPAL FINDINGS: 19 key informant interviews, 12 in
      depth interviews and 14 focus group discussions targeting care-givers, opinion
      leaders, and formal and informal health care providers were conducted. Monthly
      fever episodes and danger signs or symptoms associated with severe malaria among
      under-fives were recorded. Respondents recognized convulsions, altered
      consciousness and coma, and were aware of their risks if not treated. But, these
      symptoms were perceived to be caused by supernatural forces, and traditional
      healers were identified as primary care providers. With some delay, mothers
      eventually visited a health facility when convulsions were part of the illness,
      despite pressures against this. Although vomiting and failure to eat/suck/drink
      were associated with malaria, they were not considered as indicators of danger
      signs unless combined with another more severe symptom. Study communities were
      familiar with rectal application of medicines. CONCLUSIONS/SIGNIFICANCE:
      Communities' recognition and awareness of major symptoms of severe malaria could
      encourage action, but perceptions of their causes and poor discrimination of
      other danger signs - vomiting and failure to feed - might impede early treatment.
      An effective health education targeting parents/guardians, decision
      makers/advisors, and formal and informal care providers might be a prerequisite
      for successful introduction of rectal artemisinins as an emergency treatment.
      Role of traditional healers in delivering such medication to the community should
      be explored.

PMID- 17225857
TI  - The emergence of HIV transmitted resistance in Botswana: "when will the WHO
      detection threshold be exceeded?".
AB  - BACKGROUND: The Botswana antiretroviral program began in 2002 and currently
      treats 42,000 patients, with a goal of treating 85,000 by 2009. The World Health
      Organization (WHO) has begun to implement a surveillance system for detecting
      transmitted resistance that exceeds a threshold of 5%. However, the WHO has not
      determined when this threshold will be reached. Here we model the Botswana
      government's treatment plan and predict, to 2009, the likely stochastic evolution
      of transmitted resistance. METHODS: We developed a model of the stochastic
      evolution of drug-resistant strains and formulated a birth-death Master equation.
      We analyzed this equation to obtain an analytical solution of the probabilistic
      evolutionary trajectory for transmitted resistance, and used treatment and
      demographic data from Botswana. We determined the temporal dynamics of
      transmitted resistance as a function of: (i) the transmissibility (i.e., fitness)
      of the drug-resistant strains that may evolve and (ii) the rate of acquired
      resistance. RESULTS: Transmitted resistance in Botswana will be unlikely to
      exceed the WHO's threshold by 2009 even if the rate of acquired resistance is
      high and the strains that evolve are half as fit as the wild-type strains.
      However, we also found that transmission of drug-resistant strains in Botswana
      could increase to approximately 15% by 2009 if the drug-resistant strains that
      evolve are as fit as the wild-type strains. CONCLUSIONS: Transmitted resistance
      will only be detected by the WHO (by 2009) if the strains that evolve are
      extremely fit and acquired resistance is high. Initially after a treatment
      program is begun a threshold lower than 5% should be used; and we advise that
      predictions should be made before setting a threshold. Our results indicate that
      it may be several years before the WHO's surveillance system is likely to detect
      transmitted resistance in other resource-poor countries that have significantly
      less ambitious treatment programs than Botswana.

PMID- 17225858
TI  - A group-1 grass pollen allergen influences the outcome of pollen competition in
      maize.
AB  - Worldwide, 400 million people suffer from hay fever and seasonal asthma. The
      major causative agents of these allergies are pollen specific proteins called the
      group-1 grass pollen allergens. Although details of their antigenicity have been
      studied for 40 years with an eye towards immunotherapy, their function in the
      plant has drawn scant attention. Zea m 1 constitutes a class of abundant grass
      pollen allergens coded for by several genes that loosen the walls of grass cells,
      including the maize stigma and style. We have examined the impact of a transposon
      insertion into one of these genes (EXPB1, the most abundant isoform of Zea m 1)
      on the production of Zea m 1 protein, pollen viability, and pollen tube growth,
      both in vitro and in vivo. We also examined the effect of the insertional
      mutation on the competitive ability of the pollen by experimentally varying the
      sizes of the pollen load deposited onto stigmas using pollen from heterozygous
      plants and then screening the progeny for the presence of the transposon using
      PCR. We found that the insertional mutation reduced the levels of Zea m 1 in
      maize pollen, but had no effect on pollen viability, in vitro pollen tube growth
      or the proportion of progeny sired when small pollen loads are deposited onto
      stigmas. However, when large pollen loads are deposited onto the stigmas, the
      transposon mutation is vastly underrepresented in the progeny, indicating that
      this major pollen allergen has a large effect on pollen tube growth rates in
      vivo, and plays an important role in determining the outcome of the pollen-pollen
      competition for access to the ovules. We propose that the extraordinary abundance
      (4% of the extractable protein in maize pollen) of this major pollen allergen is
      the result of selection for a trait that functions primarily in providing
      differential access to ovules.

PMID- 17225856
TI  - Recruitment and activation of RSK2 by HIV-1 Tat.
AB  - The transcriptional activity of the integrated HIV provirus is dependent on the
      chromatin organization of the viral promoter and the transactivator Tat. Tat
      recruits the cellular pTEFb complex and interacts with several chromatin
      modifying enzymes, including the histone acetyltransferases p300 and PCAF. Here,
      we examined the interaction of Tat with activation-dependent histone kinases,
      including the p90 ribosomal S6 kinase 2 (RSK2). Dominant-negative RSK2 and
      treatment with a small-molecule inhibitor of RSK2 kinase activity inhibited the
      transcriptional activity of Tat, indicating that RSK2 is important for Tat
      function. Reconstitution of RSK2 in cells from subjects with a genetic defect in
      RSK2 expression (Coffin-Lowry syndrome) enhanced Tat transactivation. Tat
      interacted with RSK2 and activated RSK2 kinase activity in cells. Both properties
      were lost in a mutant Tat protein (F38A) that is deficient in HIV
      transactivation. Our data identify a novel reciprocal regulation of Tat and RSK2
      function, which might serve to induce early changes in the chromatin organization
      of the HIV LTR.

PMID- 17225859
TI  - No intra-locus sexual conflict over reproductive fitness or ageing in field
      crickets.
AB  - Differences in the ways in which males and females maximize evolutionary fitness
      can lead to intra-locus sexual conflict in which genes delivering fitness
      benefits to one sex are costly when expressed in the other. Trade-offs between
      current reproductive effort and future reproduction and survival are fundamental
      to the evolutionary biology of ageing. This leads to the prediction that sex
      differences in the optimization of age-dependent reproductive effort may generate
      intra-locus sexual conflict over ageing rates. Here we test for intra-locus
      sexual conflict over age-dependent reproductive effort and longevity in the black
      field cricket, Teleogryllus commodus. Using a half-sib breeding design, we show
      that the most important components of male and female reproductive effort (male
      calling effort and the number of eggs laid by females) were positively
      genetically correlated, especially in early adulthood. However, the genetic
      relationships between longevity and reproductive effort were different for males
      and females, leading to low genetic covariation between male and female
      longevity. The apparent absence of intra-locus sexual conflict over ageing
      suggests that male and female longevity can evolve largely independently of one
      another.

PMID- 17225860
TI  - Human neural stem cells over-expressing VEGF provide neuroprotection,
      angiogenesis and functional recovery in mouse stroke model.
AB  - BACKGROUND: Intracerebral hemorrhage (ICH) is a lethal stroke type. As mortality
      approaches 50%, and current medical therapy against ICH shows only limited
      effectiveness, an alternative approach is required, such as stem cell-based cell
      therapy. Previously we have shown that intravenously transplanted human neural
      stem cells (NSCs) selectively migrate to the brain and induce behavioral recovery
      in rat ICH model, and that combined administration of NSCs and vascular
      endothelial growth factor (VEGF) results in improved structural and functional
      outcome from cerebral ischemia. METHODS AND FINDINGS: We postulated that human
      NSCs overexpressing VEGF transplanted into cerebral cortex overlying ICH lesion
      could provide improved survival of grafted NSCs, increased angiogenesis and
      behavioral recovery in mouse ICH model. ICH was induced in adult mice by
      unilateral injection of bacterial collagenase into striatum. HB1.F3.VEGF human
      NSC line produced an amount of VEGF four times higher than parental F3 cell line
      in vitro, and induced behavioral improvement and 2-3 fold increase in cell
      survival at two weeks and eight weeks post-transplantation. CONCLUSIONS: Brain
      transplantation of F3 human NSCs over-expressing VEGF near ICH lesion sites
      provided differentiation and survival of grafted human NSCs and renewed
      angiogenesis of host brain and functional recovery of ICH animals. These results
      suggest a possible application of the human neural stem cell line, which is
      genetically modified to over-express VEGF, as a therapeutic agent for ICH-stroke.

PMID- 17225862
TI  - C4b binding protein binds to CD154 preventing CD40 mediated cholangiocyte
      apoptosis: a novel link between complement and epithelial cell survival.
AB  - Activation of CD40 on hepatocytes and cholangiocytes is critical for amplifying
      Fas-mediated apoptosis in the human liver. C4b-Binding Protein (C4BP) has been
      reported to act as a potential surrogate ligand for CD40, suggesting that it
      could be involved in modulating liver epithelial cell survival. Using surface
      plasmon resonance (BiaCore) analysis supported by gel filtration we have shown
      that C4BP does not bind CD40, but it forms stable high molecular weight complexes
      with soluble CD40 ligand (sCD154). These C4BP/sCD154 complexes bound efficiently
      to immobilised CD40, but when applied to cholangiocytes they failed to induce
      apoptosis or proliferation or to activate NFkB, AP-1 or STAT 3, which are
      activated by sCD154 alone. Thus C4BP can modulate CD40/sCD154 interactions by
      presenting a high molecular weight multimeric sCD154/C4BP complex that suppresses
      critical intracellular signalling pathways, permitting cell survival without
      inducing proliferation. Immunohistochemistry demonstrated co-localisation and
      enhanced expression of C4BP and CD40 in human liver cancers. These findings
      suggest a novel pathway whereby components of the complement system and TNF
      ligands and receptors might be involved in modulating epithelial cell survival in
      chronic inflammation and malignant disease.

PMID- 17225861
TI  - Evolutionary history of LINE-1 in the major clades of placental mammals.
AB  - BACKGROUND: LINE-1 constitutes an important component of mammalian genomes. It
      has a dynamic evolutionary history characterized by the rise, fall and
      replacement of subfamilies. Most data concerning LINE-1 biology and evolution are
      derived from the human and mouse genomes and are often assumed to hold for all
      placentals. METHODOLOGY: To examine LINE-1 relationships, sequences from the 3'
      region of the reverse transcriptase from 21 species (representing 13 orders
      across Afrotheria, Xenarthra, Supraprimates and Laurasiatheria) were obtained
      from whole genome sequence assemblies, or by PCR with degenerate primers. These
      sequences were aligned and analysed. PRINCIPAL FINDINGS: Our analysis reflects
      accepted placental relationships suggesting mostly lineage-specific LINE-1
      families. The data provide clear support for several clades including Glires,
      Supraprimates, Laurasiatheria, Boreoeutheria, Xenarthra and Afrotheria. Within
      the afrotherian LINE-1 (AfroLINE) clade, our tree supports Paenungulata,
      Afroinsectivora and Afroinsectiphillia. Xenarthran LINE-1 (XenaLINE) falls sister
      to AfroLINE, providing some support for the Atlantogenata (Xenarthra+Afrotheria)
      hypothesis. SIGNIFICANCE: LINEs and SINEs make up approximately half of all
      placental genomes, so understanding their dynamics is an essential aspect of
      comparative genomics. Importantly, a tree of LINE-1 offers a different view of
      the root, as long edges (branches) such as that to marsupials are shortened
      and/or broken up. Additionally, a robust phylogeny of diverse LINE-1 is essential
      in testing that site-specific LINE-1 insertions, often regarded as homoplasy-free
      phylogenetic markers, are indeed unique and not convergent.

PMID- 17225863
TI  - Gene sampling strategies for multi-locus population estimates of genetic
      diversity (theta).
AB  - BACKGROUND: Theoretical work suggests that data from multiple nuclear loci
      provide better estimates of population genetic parameters than do single loci,
      but just how many loci are needed and how much sequence is required from each has
      been little explored. METHODOLOGY/PRINCIPLE FINDINGS: To investigate how much
      data is required to estimate the population genetic parameter theta (4N(e)mu)
      accurately under ideal circumstances, we simulated datasets of DNA sequences
      under three values of theta per site (0.1, 0.01, 0.001), varying in both the
      total number of base pairs sequenced per individual and the number of equal
      length loci. From these datasets we estimated theta using the maximum likelihood
      coalescent framework implemented in the computer program Migrate. Our results
      corroborated the theoretical expectation that increasing the number of loci
      impacted the accuracy of the estimate more than increasing the sequence length at
      single loci. However, when the value of theta was low (0.001), the per-locus
      sequence length was also important for estimating theta accurately, something
      that has not been emphasized in previous work. CONCLUSIONS/SIGNIFICANCE: Accurate
      estimation of theta required data from at least 25 independently evolving loci.
      Beyond this, there was little added benefit in terms of decreasing the squared
      coefficient of variation of the coalescent estimates relative to the extra effort
      required to sample more loci.

PMID- 17225864
TI  - High-efficiency FLP and PhiC31 site-specific recombination in mammalian cells.
AB  - DNA site-specific recombinases (SSRs) such as Cre, FLPe, and phiC31, are powerful
      tools for analyzing gene function in vertebrates. While the availability of
      multiple high-efficiency SSRs would facilitate a wide array of genomic
      engineering possibilities, efficient recombination in mammalian cells has only
      been observed with Cre recombinase. Here we report the de novo synthesis of mouse
      codon-optimized FLP (FLPo) and PhiC31 (PhiC31o) SSRs, which result in
      recombination efficiencies similar to Cre.

PMID- 17225865
TI  - Sp1 is essential for p16 expression in human diploid fibroblasts during
      senescence.
AB  - BACKGROUND: p16(INK4a) tumor suppressor protein has been widely proposed to
      mediate entrance of the cells into the senescent stage. Promoter of p16(INK4a)
      gene contains at least five putative GC boxes, named GC-I to V, respectively. Our
      previous data showed that a potential Sp1 binding site, within the promoter
      region from -466 to -451, acts as a positive transcription regulatory element.
      These results led us to examine how Sp1 and/or Sp3 act on these GC boxes during
      aging in cultured human diploid fibroblasts. METHODOLOGY/PRINCIPAL FINDINGS:
      Mutagenesis studies revealed that GC-I, II and IV, especially GC-II, are
      essential for p16(INK4a) gene expression in senescent cells. Electrophoretic
      mobility shift assays (EMSA) and ChIP assays demonstrated that both Sp1 and Sp3
      bind to these elements and the binding activity is enhanced in senescent cells.
      Ectopic overexpression of Sp1, but not Sp3, induced the transcription of
      p16(INK4a). Both Sp1 RNAi and Mithramycin, a DNA intercalating agent that
      interferes with Sp1 and Sp3 binding activities, reduced p16(INK4a) gene
      expression. In addition, the enhanced binding of Sp1 to p16(INK4a) promoter
      during cellular senescence appeared to be the result of increased Sp1 binding
      affinity, not an alteration in Sp1 protein level. CONCLUSIONS/SIGNIFICANCE: All
      these results suggest that GC- II is the key site for Sp1 binding and increase of
      Sp1 binding activity rather than protein levels contributes to the induction of
      p16(INK4a) expression during cell aging.

PMID- 17225866
TI  - Epidemic enhancement in partially immune populations.
AB  - We observe that a pathogen introduced into a population containing individuals
      with acquired immunity can result in an epidemic longer in duration and/or larger
      in size than if the pathogen were introduced into a naive population. We call
      this phenomenon "epidemic enhancement," and use simple dynamical models to show
      that it is a realistic scenario within the parameter ranges of many common
      infectious diseases. This finding implies that repeated pathogen introduction or
      intermediate levels of vaccine coverage can lead to pathogen persistence in
      populations where extinction would otherwise be expected.

PMID- 17225868
TI  - Prevention of neutrophil migration ameliorates rat lung allograft rejection.
AB  - Chemokines activate and recruit specific leukocyte subpopulations. We sought to
      determine whether neutrophil migration, which can contribute to the development
      of ischemia-reperfusion injury, correlates with lung allograft rejection.
      Orthotopic left lung allotransplantation was performed from Brown Norway (donor)
      to Fisher 344 (recipient) rats. Because the role of activated neutrophils in the
      development of allograft rejection is believed to be biphasic, we used specific
      CXC receptor inhibition with antileukinate in 2 dosing regimens. Recipients were
      allocated into 4 groups; A (early administration) received 2 doses of
      antileukinate (10.0 mg/kg) intramuscularly 24 h before and immediately after
      transplantation; B (continuous administration) continuously received
      antileukinate intraperitoneally (10.0 mg/kg/day) for 7 days after surgery. Groups
      A or B were compared with individual controls that received PBS alone. The
      progression of rejection was assessed radiographically. Histologic evaluation of
      allograft rejection based on pathologic rejection grade, performed on day 7,
      demonstrated significantly lower histologic rejection in group B compared with
      the control group (2.1+/-1.0 vs. 3.3+/-0.5; P=0.018), whereas there was no
      significant difference in group A compared with the control group. There were no
      significant differences between the aeration scores of groups A or B compared
      with their control groups. Our data suggest that neutrophils may play a promoting
      role in the development of allograft rejection, and blockage of neutrophil
      migration may suppress acute lung allograft rejection.

PMID- 17225869
TI  - CD151 gene delivery activates PI3K/Akt pathway and promotes neovascularization
      after myocardial infarction in rats.
AB  - Our previous study showed that CD151 promotes neovascularization and improves
      blood perfusion in a rat hindlimb ischemia model. In this study, we investigated
      whether CD151 promotes neovascularization and improves ventricular function after
      myocardial infarction in rats and the mechanisms involved. Rats were subjected to
      sham surgery or coronary artery ligation. We used rAAV for direct delivery of the
      human CD151 gene into the rat myocardium. At 4 weeks after coronary artery
      ligation, human CD151 mRNA was detected using RT-PCR. Measurement of capillary
      density was evaluated using immunostaining for von Willebrand factor, and
      hemodynamic variables and physiological parameters were monitored. Western blot
      analysis for CD151, PI3K, phosphor-Akt, total Akt, phosphor-eNOS, and total eNOS
      was performed. In addition, we also observed the effect of CD151 on the
      expression of VEGF using Western blot analysis. CD151 gene delivery could
      increase the expression of CD151 at gene and protein levels. Overexpression of
      CD151 could increase the number of microvessels in the ischemic myocardium and
      significantly improved the hemodynamic variables after myocardial infarction. In
      addition, CD151 could activate the PI3K pathway, including activation of Akt and
      eNOS, but did not affect the expression of VEGF. This study suggested that CD151
      could promote neovascularization and improve ventricular function after
      myocardial infarction in rats. The mechanism may be that CD151 can activate the
      PI3K pathway and promote neovascularization via the PI3K pathway, without
      affecting ischemia-induced VEGF expression.

PMID- 17225867
TI  - Adenoviral gene delivery to primary human cutaneous cells and burn wounds.
AB  - The adenoviral transfer of therapeutic genes into epidermal and dermal cells is
      an interesting approach to treat skin diseases and to promote wound healing. The
      aim of this study was to assess the in vitro and in vivo transfection efficacy in
      skin and burn wounds after adenoviral gene delivery. Primary keratinocytes (HKC),
      fibroblasts (HFB), and HaCaT cells were transfected using different
      concentrations of an adenoviral construct (eGFP). Transfection efficiency and
      cytotoxicity was determined up to 30 days. Expression was quantified by FACS
      analysis and fluorimeter. Cytotoxicity was measured using the trypan blue
      exclusion method. 45 male Sprague Dawley rats received 2x10(8) pfu of Ad5-CMV
      LacZ or carrier control intradermally into either superficial partial thickness
      scald burn or unburned skin. Animals were euthanized after 48 h, 7 or 14 days
      posttreatment. Transgene expression was assessed using immunohistochemistry and
      bioluminescent assays. The highest transfection rate was observed 48 h
      posttransfection: 79% for HKC, 70% for HFB, and 48% for HaCaT. The eGFP
      expression was detectable in all groups over 30 days (P>0.05). Cytotoxic effects
      of the adenoviral vector were observed for HFB after 10 days and HaCaT after 30
      days. Reporter gene expression in vivo was significantly higher in burned skin
      compared with unburned skin (P=0,004). Gene expression decreases from 2 to 7 days
      with no significant expression after 14 days. This study demonstrates that
      effective adenoviral-mediated gene transfer of epidermal primary cells and cell
      lines is feasible. Ex vivo gene transfer in epithelial cells might have promise
      for the use in severely burned patients who receive autologous keratinocyte
      sheets. Transient cutaneous gene delivery in burn wounds using adenoviral vectors
      causes significant concentrations in the wound tissue for at least 1 week. Based
      on these findings, we hypothesize that transient cutaneous adenoviral gene
      delivery of wound healing promoting factors has potential for clinical
      application.

PMID- 17225870
TI  - Activation of poly(ADP-ribose) polymerase by myocardial ischemia and coronary
      reperfusion in human circulating leukocytes.
AB  - Reactive free radical and oxidant production leads to DNA damage during
      myocardial ischemia/reperfusion. Consequent overactivation of poly(ADP-ribose)
      polymerase (PARP) promotes cellular energy deficit and necrosis. We hypothesized
      that PARP is activated in circulating leukocytes in patients with myocardial
      infarction and reperfusion during primary percutaneous coronary intervention
      (PCI). In 15 patients with ST segment elevation acute myocardial infarction,
      before and after primary PCI and 24 and 96 h later, we determined serum hydrogen
      peroxide concentrations, plasma levels of the oxidative DNA adduct 8-hydroxy-2'
      deoxyguanosine (8OHdG), tyrosine nitration, PARP activation, and translocation of
      apoptosis-inducing factor (AIF) in circulating leukocytes. Plasma 8OHdG levels
      and leukocyte tyrosine nitration were rapidly increased by PCI. Similarly,
      poly(ADP-ribose) content of the leukocytes increased in cells isolated just after
      PCI, indicating immediate PARP activation triggered by reperfusion of the
      myocardium. In contrast, serum hydrogen peroxide concentrations and the
      translocation of AIF gradually increased over time and were most pronounced at 96
      h. Reperfusion-related oxidative/nitrosative stress triggers DNA damage, which
      leads to PARP activation in circulating leukocytes. Translocation of AIF and
      lipid peroxidation occurs at a later stage. These results represent the first
      direct demonstration of PARP activation in human myocardial infarction. Future
      work is required to test whether pharmacological inhibition of PARP may offer
      myocardial protection during primary PCI.

PMID- 17225871
TI  - Recombinant chimeric antibody hCAb as a novel anti-human colorectal carcinoma
      agent.
AB  - A new chimeric IgG1 antibody hCAb which could be specifically directed against a
      cell surface-associated glycoprotein of colorectal cancer cells was prepared by
      genetic engineering technology in our lab. In this study, we explored the
      potential therapeutic mechanisms and described the evaluation of hCAb directed
      against colorectal cancer. The standard 51Cr release assay showed that like many
      other clinically validated IgG1 monoclonal antibodies, hCAb primarily acts by
      antibody-dependent cell-mediated cytotoxicity (ADCC). The maximal cell lysis of
      ADCC induced by hCAb was over 50% in the presence of peripheral blood mononuclear
      cells (PBMCs). Moreover, in vivo studies showed potent antitumor effects in nude
      mice with SW480 and Hce-8693 tumor xenografts. The treatment with hCAb induced a
      dramatic reduction (over 70%) in tumor volume in comparison to untreated control
      group. Furthermore, during the period of treatment, the animals treated by hCAb
      did not show signs of wasting or other visible signs of toxicity. No obvious
      tissue damage in vital organs was detected. The chimeric antibody hCAb may be a
      promising candidate in the treatment of human colorectal cancer. This study can
      provide a reference for the potential application of hCAb in clinical trial.

PMID- 17225873
TI  - Real-time PCR and linkage studies to identify carriers presenting HPRT deleted
      gene.
AB  - Lesch-Nyhan syndrome (LNS) is an X-linked genetic disorder resulting in
      hyperuricemia, choreoathetosis, mental retardation, and self-injurious behavior.
      It is caused by loss of activity of the ubiquitous enzyme hypoxanthine-guanine
      phosphoribosyltransferase (HPRT). The biochemical analysis of residual HPRT
      activity in patients' red blood cells is the first step in LNS diagnosis, and it
      precedes molecular study to discover the specific mutation. Unfortunately,
      biochemical diagnosis of healthy carriers is difficult because HPRT enzymatic
      activity in blood cells is similar in LNS carriers and in healthy people; genetic
      tests can help reveal mutations at the genomic or cDNA level, whereas gross
      deletions involving the first or last exons of HPRT gene are not detectable.
      Until now, a test based on 6-thioguanine-resistant phenotype of HPRT mutant cells
      from LNS patients is the only method accepted for the diagnosis of any kind of
      mutation in carriers. In this work, we introduce a new approach to identify
      carriers of large deletions in HPRT gene using real-time PCR. Results were
      validated in a blinded manner with a linkage study and with results obtained in
      Italian families previously analyzed with selective medium test. Real-time PCR
      analysis clearly confirmed the results obtained by selective medium; linkage data
      strengthened real time results, allowing us to follow the allele with the mutated
      HPRT through the family pedigree. We hope that the real-time PCR approach will
      provide a useful and reliable method to diagnose LNS carriers of large deletions
      in HPRT gene.

PMID- 17225872
TI  - Retinoic acid, GABA-ergic, and TGF-beta signaling systems are involved in human
      cleft palate fibroblast phenotype.
AB  - During embryogenesis, a complex interplay between extracellular matrix (ECM)
      molecules, regulatory molecules, and growth factors mediates morphogenetic
      processes involved in palatogenesis. Transforming growth factor-beta (TGF-beta),
      retinoic acid (RA), and gamma-aminobutyric acid (GABA)ergic signaling systems are
      also potentially involved. Using [3H]glucosamine and [35S]methionine
      incorporation, anion exchange chromatography, semiquantitative radioactive RT
      PCR, and a TGF-beta binding assay, we aimed to verify the presence of phenotypic
      differences between primary cultures of secondary palate (SP) fibroblasts from 2
      year-old subjects with familial nonsyndromic cleft lip and/or palate (CLP-SP
      fibroblasts) and age-matched normal SP (N-SP) fibroblasts. The effects of RA-
      which, at pharmacologic doses, induces cleft palate in newborns of many species-
      were also studied. We found an altered ECM production in CLP-SP fibroblasts that
      synthesized and secreted more glycosaminoglycans (GAGs) and fibronectin (FN)
      compared with N-SP cells. In CLP-SP cells, TGF-beta3 mRNA expression and TGF-beta
      receptor number were higher and RA receptor-alpha (RARA) gene expression was
      increased. Moreover, we demonstrated for the first time that GABA receptor
      (GABRB3) mRNA expression was upregulated in human CLP-SP fibroblasts. In N-SP and
      CLP-SP fibroblasts, RA decreased GAG and FN secretion and increased TGF-beta3
      mRNA expression but reduced the number of TGF-beta receptors. TGF-beta receptor
      type I mRNA expression was decreased, TGF-beta receptor type II was increased,
      and TGF-beta receptor type III was not affected. RA treatment increased RARA gene
      expression in both cell populations but upregulated GABRB3 mRNA expression only
      in N-SP cells. These results show that CLP-SP fibroblasts compared with N-SP
      fibroblasts exhibit an abnormal phenotype in vitro and respond differently to RA
      treatment, and suggest that altered crosstalk between RA, GABAergic, and TGF-beta
      signaling systems could be involved in human cleft palate fibroblast phenotype.

PMID- 17225875
TI  - CYP2D6 polymorphisms in patients with porphyrias.
AB  - The cytochrome P-450 (CYP) isoenzymes, a superfamily of heme proteins which are
      the terminal oxidases of the mixed function oxidases system, metabolize more than
      70% of all clinically approved drugs. The highly polymorphic CYP2D6 isoform
      metabolizes more than 25% of most common drugs, and the phenotypes of the 70-plus
      allelic variants range from compromised to excessive enzymatic activity.
      Porphyrias are a group of inherited or acquired metabolic disorders of heme
      biosynthesis, due to a specific decrease in the activity of one of the enzymes of
      the heme pathway. Clinical signs and symptoms of porphyrias are frequently
      associated with exposure to precipitating agents, including clinically approved
      drugs. CYP enzymes, including CYP2D6, participate in the metabolism of some
      porphyrinogenic drugs, leading to the deregulation of heme biosynthesis.
      Considering that some of the drugs not recommended for use in porphyric patients
      are metabolized by CYP2D6, the presence of CYP2D6 polymorphisms in porphyric
      patients would influence the triggering of the disease when these individuals
      receive a precipitating agent that is metabolized by CYP2D6. To investigate
      CYP2D6 polymorphisms in porphyric patients, healthy Argentinean volunteers,
      porphyric patients, and a group of individuals with high levels of iron were
      studied. Results indicated that the CYP2D6*3 and CYP2D6*4 alleles, in particular,
      would be linked to the onset of disease. Predictive genotyping for CYP2D6 in
      porphyric patients holds promise as a method to improve the clinical efficacy of
      drug therapy and to personalize drug administration for these patients.

PMID- 17225874
TI  - Passive immunization to outer membrane proteins MLP and PAL does not protect mice
      from sepsis.
AB  - Multiple older studies report that immunoglobulin directed to rough mutant
      bacteria, such as E. coli J5, provides broad protection against challenge with
      heterologous strains of Gram-negative bacteria. This protection was initially
      believed to occur through binding of immunoglobulin to bacterial
      lipopolysaccharide (LPS). However, hundreds of millions of dollars have been
      invested in attempting to develop clinically-effective anti-LPS monoclonal
      antibodies without success, and no study has shown that IgG from this antiserum
      binds LPS. Identification of the protective mechanism would facilitate
      development of broadly protective human monoclonal antibodies for treating
      sepsis. IgG from this antiserum binds 2 bacterial outer membrane proteins: murein
      lipoprotein (MLP) and peptidoglycan-associated lipoprotein (PAL). Both of these
      outer membrane proteins are highly conserved, have lipid domains that are
      anchored in the bacterial membrane, are shed from bacteria in blebs together with
      LPS, and activate cells through Toll-like receptor 2. Our goal in the current
      work was to determine if passive immunization directed to MLP and PAL protects
      mice from Gram-negative sepsis. Neither monoclonal nor polyclonal IgG directed to
      MLP or PAL conferred survival protection in 3 different models of sepsis: cecal
      ligation and puncture, an infected burn model, and an infected fibrin clot model
      mimicking peritonitis. Our results are not supportive of the hypothesis that
      either anti-MLP or anti-PAL IgG are the protective antibodies in the previously
      described anti-rough mutant bacterial antisera. These studies suggest that a
      different mechanism of protection is involved.

PMID- 17225877
TI  - Endoscopy by nonphysicians.

PMID- 17225878
TI  - Recent insights into the cellular mechanisms of acute pancreatitis.
AB  - In acute pancreatitis, initiating cellular events causing acinar cell injury
      includes co-localization of zymogens with lysosomal hydrolases, leading to
      premature enzyme activation and pathological exocytosis of zymogens into the
      interstitial space. This is followed by processes that accentuate cell injury;
      triggering acute inflammatory mediators, intensifying oxidative stress,
      compromising the microcirculation and activating a neurogenic feedback. Such
      localized events then progress to a systemic inflammatory response leading to
      multiorgan dysfunction syndrome with resulting high morbidity and mortality. The
      present review discusses some of the most recent insights into each of these
      cellular processes postulated to cause or propagate the process of acute
      pancreatitis, and also the role of alcohol and genetics.

PMID- 17225880
TI  - Prevalence, impact and attitudes toward lower gastrointestinal dysmotility and
      sensory symptoms, and their treatment in Canada: A descriptive study.
AB  - OBJECTIVES: To investigate the impact of lower gastrointestinal (GI) symptoms in
      the general Canadian population, and to explore patient satisfaction with
      traditional therapies and the level of patient interest in new treatments.
      patients and METHODS: Stage 1: A telephone survey of a weighted sample of 1000
      adults (18 years of age or older) was conducted to determine the prevalence of
      five GI symptoms--abdominal pain, abdominal discomfort, bloating, constipation or
      constipation with occasional diarrhea- that were present for 12 weeks or more
      (not necessarily consecutive) over the past year. Respondents with only abdominal
      pain were excluded. Stage 2: A telephone survey of 689 women (18 to 64 years of
      age), experiencing the GI symptoms described in stage 1, was conducted to assess
      symptom impact and treatment satisfaction. RESULTS: Overall, 5.2% of the Canadian
      population (2.3% men and 7.9% women) experienced one or more lower GI symptoms
      (excluding those reporting abdominal pain alone). In stage 2, 26.2% of
      respondents had previously been diagnosed with irritable bowel syndrome. Overall,
      78.1% of participants experienced two or more symptoms. Bloating was the most
      common symptom (75.3%) and abdominal pain the most bothersome and most severe.
      Over the previous three months, 13.2% of respondents missed work or school and
      28.8% were less productive. At least one physician (average of 2.2 physicians)
      was consulted for symptoms in 80.9% of respondents. Of the 63.8% women receiving
      treatment, most used nonprescription products. Patients receiving prescription
      treatments for constipation were most often dissatisfied (75%). CONCLUSIONS:
      Abdominal pain and discomfort, bloating and constipation are common, frequently
      occurring symptoms in the Canadian population and have a high burden on work
      performance and health care seeking. Most patients were dissatisfied with
      traditional therapies.

PMID- 17225879
TI  - The comparison of dexmedetomidine and midazolam used for sedation of patients
      during upper endoscopy: A prospective, randomized study.
AB  - The aim of the present prospective, randomized study was to investigate and
      compare the safety and efficacy of dexmedetomidine versus midazolam in providing
      sedation for gastroscopy. A total of 50 adult patients (25 patients receiving
      dexmedetomidine and 25 patients receiving midazolam), 18 to 60 years of age, and
      rated I and II on the American Society of Anesthesiologists physical status
      classification system were included. A brief questionnaire was used to collect
      demographic data; patients were asked to rate anxiety, satisfaction with care to
      date and expected discomfort on a visual analogue scale. The following parameters
      were measured continuously and recorded every minute: heart rate, mean arterial
      pressure, hemoglobin oxygen saturation and respiratory rate. The two groups were
      similar with regard to age, body mass index, sex, education, duration of
      endoscopy, and ethanol or tobacco use. After the procedure, full recovery time,
      mean arterial pressure, heart rate, respiratory rate and hemoglobin oxygen
      saturation levels were similar in both groups. Both groups also had low levels of
      perceived procedural gagging, discomfort and anxiety scores (P > 0.05), and high
      satisfaction levels (90.1+/-3.0 for dexmedetomidine versus 84.9+/-4.5 for
      midazolam; P > 0.05). Retching and endoscopist satisfaction were significantly
      different in patients receiving dexmedetomidine versus those receiving midazolam
      (88.8+/-6.5 versus 73.5+/-16.4, P < 0.05; and 20.6+/-4.4 versus 45.2+/-6.0; P <
      0.001). In the midazolam group, the number of patients who had adverse effects
      was higher than the dexmedetomidine group (P < 0.05). As a result,
      dexmedetomidine performed as effectively and safely as midazolam when used as a
      sedative in upper gastroscopy; it was superior to midazolam with regard to
      retching, rate of side effects and endoscopist satisfaction. It was concluded
      that dexmedetomidine may be a good alternative to midazolam to sedate patients
      for upper endoscopy.

PMID- 17225881
TI  - Preoperative alpha-fetoprotein slope is predictive of hepatocellular carcinoma
      recurrence after liver transplantation.
AB  - BACKGROUND: Liver transplantation (LT) offers a possible cure for patients with
      hepatocellular carcinoma (HCC) and cirrhosis. However, tumour progression while
      on the waiting list and tumour recurrence after LT are common. The prognostic
      significance of various pre- and postoperative variables were investigated in
      regard to tumour recurrence, with an emphasis on the slope of preoperative serum
      alpha-fetoprotein (AFP) levels. patients and METHODS: Data from 48 patients who
      had HCC diagnosed preoperatively and underwent LT at the McGill University Health
      Centre (Montreal, Quebec) were reviewed retrospectively, and possible risk
      factors for tumour recurrence were examined. RESULTS: Univariate analysis
      revealed a positive correlation between the preoperative AFP slope and vascular
      invasion (P = 0.045), total tumour diameter at explant (P = 0.040), Cancer of the
      Liver Italian Program score (P = 0.017) and recurrence-free survival (P = 0.028).
      Of the preoperative variables examined, only the preoperative AFP slope was
      identified as an independent predictor of tumour recurrence by multivariate
      analysis. Receiver operating characteristic analysis showed that the best
      discriminant cut-off value, calculated as the value of the maximized likelihood
      ratio, was preoperative AFP slope greater than 50 microg/L per month. At this cut
      off, sensitivity was 36%, and specificity was 97%. Patients with a preoperative
      AFP slope greater than 50 microg/L per month had a much worse one-year recurrence
      free survival rate than those with a preoperative AFP slope 50 microg/L per month
      or less (40% versus 90%, P < 0.001). CONCLUSIONS: These results suggest that the
      preoperative AFP slope is an important predictor of HCC recurrence after LT and
      should be examined in future studies of patients receiving LT for HCC.

PMID- 17225883
TI  - Times have changed--Is it time to consider restructuring the CAG?

PMID- 17225884
TI  - Lanthanide reagents in solid phase synthesis.
AB  - From solid-supported ytterbium(III) catalysts to linkers cleaved by electron
      transfer from samarium(II) species, lanthanide reagents are beginning to find
      widespread application in solid phase organic synthesis. This tutorial review
      introduces the use of lanthanide(III) Lewis acids and lanthanide(IV) oxidants in
      solid phase chemistry before concentrating on the growing use of lanthanide(II)
      reagents in the area.

PMID- 17225885
TI  - Synthesis and application in asymmetric catalysis of camphor-based pyridine
      ligands.
AB  - This tutorial review deals with the synthesis and application in asymmetric
      catalysis of camphor-based pyridine ligands. These ligands can be roughly divided
      into two groups: those in which the camphor is annulated in the 2,3-positions to
      the beta-face of the pyridine ring and those in which the pyridine is contained
      as a pendant on the C2 or C3 of the camphor framework. Camphor-based pyridine
      ligands can also contain other donor centers located on the pyridine ring or
      camphor skeleton. Some of these ligands have provided interesting
      enantioselectivities in several asymmetric reactions, such as S(N)2' reactions,
      allylic oxidations, carbonyl additions with organozinc reagents and
      hydrogenations. This review contains a lot of chemistry on ligand synthesis and
      readers will find it of value and also perhaps an inspiration for the development
      of more active and improved versions.

PMID- 17225886
TI  - Near edge X-ray absorption fine structure spectroscopy as a tool to probe
      electronic and structural properties of thin organic films and liquids.
AB  - Synchrotron-based spectroscopic techniques have contributed significantly to a
      better understanding of the properties of materials on the macroscopic and
      microscopic scale over the last decades. They can be applied to samples from a
      diversity of fields, including Biology, Life Sciences, Chemistry and Materials.
      One of these techniques is Near Edge X-Ray Absorption Fine Structure (NEXAFS)
      spectroscopy, revealing electronic structure and information on the orientation
      of adsorbed molecules. The present article describes the basics of the technique
      and the progress it has made over the last three decades, and summarizes some of
      its more recent developments and applications. This tutorial review article
      should be accessible for novices to the field from Physics, Chemistry, Biology,
      Materials, and the Life Sciences, interested in thin organic films and liquid
      systems.

PMID- 17225882
TI  - Colonic squamous cell carcinoma in ulcerative colitis: Report of a case and
      review of the literature.
AB  - Squamous cell carcinoma (SCC) is a rare neoplasm in the colorectum. A case of SCC
      rising from an area of squamous metaplasia in the rectum is presented in a
      patient with long-standing ulcerative colitis and perianal warts. This is the
      first report in the literature describing the evolution of squamous metaplasia in
      the colonic mucosa into invasive carcinoma over time. Related literature on
      colorectal SCC and squamous metaplasia, and their relationships with inflammatory
      bowel disease and human papilloma virus, is reviewed.

PMID- 17225887
TI  - Sulfur: not a "silent" element any more.
AB  - To understand the many important functions of sulfur, a ubiquitous element in
      biological systems, in the environment and for industrial applications, detailed
      analyses are needed. Characterization of the variety of sulfur functional groups
      in a natural sample, often occurring in a wide range of oxidation states, became
      possible when the development of dedicated X-ray absorption near-edge structure
      (XANES) spectroscopy started in the mid-1980s. This tutorial review provides an
      overview of sulfur XANES spectroscopic investigations into the role of sulfur in
      all kinds of natural samples, from sediment and oil to marine-archaeological wood
      and plants.

PMID- 17225888
TI  - Synthetic ion channels and pores (2004-2005).
AB  - This critical review covers synthetic ion channels and pores created between
      January 2004 and December 2005 comprehensively. The discussion of a rich
      collection of structural motifs may particularly appeal to organic, biological,
      supramolecular and polymer chemists. Functions addressed include ion selectivity
      and molecular recognition, as well as responsiveness to light, heat, voltage and
      membrane composition. The practical applications involved concern certain topics
      in medicinal chemistry (antibiotics, drug delivery), catalysis and sensing. An
      introduction to principles and methods is provided for the non-specialist; some
      new sources of inspiration from fields beyond chemistry are highlighted.

PMID- 17225889
TI  - Cellulose--model films and the fundamental approach.
AB  - This critical review describes the recent arrival of ultrathin films of
      cellulose. The methodology of preparation as well as the applications of the
      films for fundamental research is fully covered. The review places cellulose in a
      wider scientific context where cellulose research is no longer a field of
      interest for specialised scientists only. Cellulose and cellulosic materials
      should interest communities such as biochemists, physical chemists, surface
      chemists, organic chemists, polymer chemists and also physicists working close
      the disciplines mentioned. (149 references.).

PMID- 17225890
TI  - Dipolar interactions and hydrogen bonding in supramolecular aggregates:
      understanding cooperative phenomena for 1st hyperpolarizability.
AB  - Weak intermolecular forces like dipolar interactions and hydrogen-bonding lead to
      a variety of different packing arrangements of molecules in crystals and self
      assemblies. Such differences in the arrangements change the extent of excitonic
      splitting and excitation spectra in the multichromophore aggregates. In this
      tutorial review, the role of such interactions in fine tuning the linear and 1st
      non-linear optical (NLO) responses in molecular aggregates are discussed. The non
      additivity of these optical properties arise specifically due to such cooperative
      interactions. Calculations performed on dimers, trimers and higher aggregates for
      model systems provide insights into the interaction mechanisms and strategies to
      enhance the 1st hyperpolarizabilities of pi-conjugated molecular assemblies.
      Flexible dipole orientations in the alkane bridged chromophores show odd-even
      variations in their second-harmonic responses that are explained through their
      dipolar interactions in different conformations. Parameters for the optical
      applications of molecules arranged in constrained geometry, like in
      Calix[n]arene, have been elucidated. We also highlight the recent developments in
      this field of research together with their future prospects.

PMID- 17225891
TI  - Electrochemical oxidation of organic pollutants for the wastewater treatment:
      direct and indirect processes.
AB  - In recent years, there has been increasing interest in finding innovative
      solutions for the efficient removal of contaminants from water, soil and air. The
      present tutorial review summarizes the results of an extensive selection of
      papers dealing with electrochemical oxidation, which is proposed as an
      alternative for treating polluted wastes. Both the direct and indirect approaches
      are considered, and the role of electrode materials is discussed together with
      that of other experimental parameters. Apart from discussing the possibility of
      removing selected contaminants from water using different anodes, efficiency
      rates for pollutant removal have been collected, the dependence of these rates on
      operational conditions advantages and disadvantages determining the further full
      scale commercial application.

PMID- 17225892
TI  - The carbene insertion methodology for the catalytic functionalization of
      unreactive hydrocarbons: no classical C-H activation, but efficient C-H
      functionalization.
AB  - This contribution intends to highlight the use of the metal-catalyzed
      functionalization of unreactive carbon-hydrogen bonds by the carbene insertion
      methodology, that employs diazo compounds as the carbene source.

PMID- 17225893
TI  - Synthesis and coordination chemistry of an alkyne functionalised
      bis(pyrazolyl)methane ligand.
AB  - The alkyne functionalised bidentate N-donor ligand (2
      propargyloxyphenyl)bis(pyrazolyl)methane was prepared in high yield from the
      reaction of (2-hydroxyphenyl)bis(pyrazolyl)methane with propargyl bromide in the
      presence of base. A series of transition-metal complexes including [MCl2] (M=Cu,
      Co, Ni, Zn, Pt), [M2](NO3)2 (M=Cu, Co, Ni, Zn), [Ag]NO3 and [Pd(dppe)](OTf)2 were
      prepared and characterised by spectroscopic techniques. In addition, ligand as
      well as the Co(II) and Zn(II) complexes [CoCl2]2, [ZnCl2] were structurally
      characterized by single-crystal X-ray diffraction. The organometallic gold(I) and
      platinum(II) acetylide complexes [Pz2CH(C6H(4)-2-OCH2C[triple bond, length as m
      dash]CAuPPh3)] and trans-[{Pz2CHC6H(4)-2-OCH2C[triple bond, length as m
      dash]C}2Pt(PPh3)2] were prepared from and [AuCl(PPh3)] and trans-[PtCl2(PPh3)2],
      respectively. Treatment of these complexes with [Pd(OTf)2(dppe)] or
      [Cu(MeCN)4]PF6 results in formation of the cationic, mixed-metal complexes, which
      were isolated (Pt/Pd, Au/Pt) or detected by electrospray mass spectrometry
      (Au/Cu, Pt/Cu).

PMID- 17225894
TI  - Encapsulation of hydride by molecular main group metal clusters: manipulating the
      source and coordination sphere of the interstitial ion.
AB  - The sequential treatment of Lewis acids with N,N'-bidentate ligands and
      thereafter with ButLi has afforded a series of hydride-encapsulating alkali metal
      polyhedra. While the use of Me3Al in conjunction with Ph(2-C5H4N)NH gives Ph(2
      C5H4N)NAlMe2 and this reacts with MeLi in thf to yield the simple 'ate complex
      Ph(2-C5H4N)NAlMe3Li.thf, the employment of an organolithium substrate capable of
      beta-hydride elimination redirects the reaction significantly. Whereas the use of
      ButLi has previously yielded a main group interstitial hydride in which H-
      exhibits micro6-coordination, it is shown here that variability in the
      coordination sphere of the encapsulated hydride may be induced by manipulation of
      the organic ligand. Reaction of (c-C6H11)(2-C5H4N)NH with Me3Al/ButLi yields [{(c
      C6H11)(2-C5H4N)N}6HLi8]+[(But2AlMe2)2Li]-, which is best viewed as incorporating
      only linear di-coordination of the hydride ion. The guanidine 1,3,4,6,7,8
      hexahydro-2H-pyrimido[1,2-a]pyrimidine (hppH) in conjunction with Me2Zn/ButLi
      yields the micro8-hydride [(hpp)6HLi8]+[But3Zn]-.0.5PhMe. Formation of the micro8
      hydride [(hpp)6HLi8]+[ButBEt3]- is revealed by employment of the system
      Et3B/ButLi. A new and potentially versatile route to interstitial hydrides of
      this class is revealed by synthesis of the mixed borohydride-lithium hydride
      species [(hpp)6HLi8]+[Et3BH]- and [(hpp)6HLi8]+[(Et3B)2H]- through the direct
      combination of hppLi with Et3BHLi.

PMID- 17225895
TI  - Solvent dependent reactivity: solvent activation vs. solvent coordination in
      alkylphosphane iron complexes.
AB  - The pyridine-derived tetrapodal tetraphosphane C5H3N[CMe(CH2PMe2)2]2 is
      susceptible to selective protonolysis of a phosphorus-carbon bond in the presence
      of iron(II) salts. Water produces dimethylphosphinic acid, Me2POH, and protonates
      the anionic remainder of the tetraphosphane. The resulting iron(II) complexes and
      (tetrafluoroborate and perchlorate salts, respectively) contain the residual
      chelate ligand in which a methyl group, derived from the ligand skeleton, is in
      agostic interaction with the metal centre, and in which Me2POH, unavailable in
      the free state owing to rapid tautomerisation, is metal-coordinated and thus
      stabilised. Full NMR details are presented, including 31P simulations. The
      reactivity towards alcohols is similar (compounds), and has been studied using
      deuterium labels (NMR). P-C bond cleavage may be suppressed only if all protic
      agents are rigorously excluded, as in the reaction of with Fe(SO3CF3)2.2CH3CN in
      acetonitrile solution, which produces the complex [Fe(NCMe)](SO3CF3)2. In it, the
      ligand acts as an NP4 coordination cap but is severely distorted from square
      pyramidal geometry. The reaction of with anhydrous ferrous bromide, FeBr2, in
      methanol again produces a dimethylphosphinic acid ester ligand, but the complex
      now contains ferric iron coordinated by a carbanionic residual chelate ligand,
      implicating H+ as the oxidising agent under these conditions. Full spectroscopic
      and X-ray structural details are presented for all compounds.

PMID- 17225896
TI  - Synthesis and reactivity studies of palladium(II) complexes containing the N
      phosphorylated iminophosphorane-phosphine ligands Ph2PCH2P{=NP(=O)(OR)2}Ph2
      (R=Et, Ph): application to the catalytic synthesis of 2,3-dimethylfuran.
AB  - Reactions of [PdCl2(COD)] with 1 equiv. of the iminophosphorane-phosphine ligands
      Ph2PCH2P{=NP(=O)(OR)2}Ph2 (R=Et, Ph) lead to the novel Pd(II) derivatives cis
      [PdCl2(kappa2-(P,N)-Ph2PCH2P{=NP(=O)(OR)2}Ph2)] (R=Et, Ph). Pd-N bond cleavage
      readily takes place upon treatment of these species with a variety of two
      electron donor ligands. By this way, complexes cis-[PdCl2(kappa1-(P)
      Ph2PCH2P{=NP(=O)(OR)2}Ph2)(L)] (R=Et, L=CNtBu, CN-2,6-C6H3Me2, py, P(OMe)3,
      P(OEt)3; R=Ph, L=CNtBu, CN-2,6-C6H3Me2, py, P(OMe)3, P(OEt)3) have been
      synthesized in high yields. The addition of two equivalents of ligands to
      dichloromethane solutions of [PdCl2(COD)] results in the formation of complexes
      trans-[PdCl2(kappa1-(P)-Ph2PCH2P{=NP(=O)(OR)2}Ph2)2] (R=Et, Ph), which can be
      converted into the dicationic species [Pd(Ph2PCH2P{=NP(=O)(OR)2}Ph2)2][SbF6]2
      (R=Et, Ph) by treatment with AgSbF6. Complex also reacts with CNtBu to afford
      trans-[Pd(kappa1(P)-Ph2PCH2P{=NP(=O)(OPh)2}Ph2)2(CNtBu)2][SbF6]2. The structures
      of and have been determined by single-crystal X-ray diffraction methods. In
      addition, the ability of these Pd(II) complexes to promote the catalytic
      cycloisomerization of (Z)-3-methylpent-2-en-4-yn-1-ol into 2,3-dimethylfuran has
      also been studied.

PMID- 17225897
TI  - On the role of the counter-ion in defining water structure and dynamics: order,
      structure and dynamics in hydrophilic and hydrophobic gadolinium salt complexes.
AB  - The crystal structures of the hydrated salts of [Gd.DOTAM]3+ and its more
      hydrophobic derivative [Gd.]3+, bearing 4 alpha-phenylethyl groups, (both Gd and
      Yb salts) are reported and compared. The nature of the anion determines the
      degree of ordering in the lattice and the extent of hydration. These effects are
      correlated with the results of 17O and 1H NMR measurements of water exchange
      dynamics in solution. With [Gd.DOTAM]3+, structural ordering or the extent of
      hydration in the hydrated lattice follows the sequence Cl->Br->I- and this order
      also defines the water exchange rate in solution: 7.3, 19.5, 33.3x10(4) s-1 (298
      K), respectively. For [Gd.]3+ salts, the measured relaxivity is determined purely
      by the outer sphere term and the water exchange rate at 298 K is very similar
      (typically 1x10(4) s-1) for chloride, bromide, iodide, acetate, triflate and
      nitrate salts, notwithstanding the different nature and extent of hydration found
      in the crystalline lattice.

PMID- 17225898
TI  - A DFT computational study of spin crossover in iron(III) and iron(II) tripodal
      imidazole complexes. A comparison of experiment with calculations.
AB  - B3LYP* functionals were used to model the sixteen iron(II) (1A, LS and 5T, HS)
      and iron(III) (2T, LS and 6A, HS) complexes of the 1:3 Schiff base condensate of
      tris(2-aminoethyl)amine and imidazole-4-carboxaldehyde, H3L1, and its
      deprotonated forms, [H2L1]1-, [HL1]2-, and [L1]3-. This ligand system is unusual
      in that [FeH3L1]3+, [FeH3L1]2+ and [FeL1]- all exhibit a spin crossover between
      100-300 K. This makes these complexes ideal for a hybrid DFT computational
      approach and provides an opportunity to refine the value of the exact exchange
      admixture parameter, c3, and to predict properties of partially protonated
      complexes that are not experimentally available. The accepted value of 0.20 is
      larger than the value of approximately 0.13 that was found to best reproduce
      experimental data in terms of spin state predictions. With iron(III) B3LYP
      calculations showed that all of the complexes were low spin at 298 K with the
      exception of [FeH3L1]3+ which is spin crossover in agreement with experimental
      results. It was also shown for iron(III) that the ligand field increased as the
      number of protons decreased. In contrast all of the iron(II) complexes were close
      to the spin crossover region regardless of protonation state. Experimental
      structures are fairly well modeled by this system in regard to the key structural
      indicators of spin state, which are the bite and trans angles. The calculated
      iron to nitrogen atom distances are always larger in the high spin form than the
      low spin form but all iron to nitrogen bond distances are larger than the
      experimental values. In general non-bonded interactions are not well modeled by
      this methodology.

PMID- 17225900
TI  - Synthesis of nonanuclear heterometallic carbide clusters. Unexpected formation of
      the [Ru6(CO)16]2-[Pt2(CO)2(dppm)2]2+ ion pair on the way to
      [Ru6C(CO)16Pt3(dppm)2].
AB  - A novel trimetallic cluster [Ru5CRh2Pt2(CO)16(dppm)2] was synthesized via
      coupling of two neutral clusters-[Ru5C(CO)15] and [Rh2Pt2(CO)6(dppm)2]. The
      structure of this mixed metal complex was established using X-ray crystallography
      and 31P NMR spectroscopy. It was found that the reaction between [Ru6C(CO)17] and
      [Pt2(CO)3(dppm)2] leads to spontaneous electron transfer between these
      polynuclear complexes and results in the formation of an unusually stable cluster
      "salt" {[Ru6(CO)16]2-[Pt2(CO)2(dppm)2]2+}, which was characterized by
      crystallographic and spectroscopic methods. Heating of the Ru6-Pt2 ion pair in an
      autoclave (145 degrees C, 15 atm N2) results in fusion of the metal frameworks to
      give a nonanuclear mixed metal [Ru6C(CO)16Pt3(dppm)2] cluster in a good yield.
      The latter complex was obtained earlier as a minor product of another thermal
      reaction and now has been additionally characterized by 31P NMR spectroscopy.

PMID- 17225899
TI  - Rhenium(V) oxocomplexes with novel pyrazolyl-based N4- and N3S-donor chelators.
AB  - The novel pyrazolyl-based ligands 3,5-Me2pz(CH2)2NH(CH2)2NH(CH2)2NH2 and
      pz*(CH2)2NH-Gly-CH2STrit (pz*=pz, 3,5-Me2pz, 4-(EtOOC)CH(2)-3,5-Me2pz) were
      synthesized, and their suitability to stabilize Re(V) oxocomplexes was evaluated
      using different starting materials, namely (NBu4)[ReOCl4], [ReOCl3(PPh3)2] and
      trans-[ReO2(py)4]Cl. Compound reacts with trans-[ReO2(py)4]Cl yielding the
      cationic compound [ReO(OMe){3,5-Me2pz(CH2)2N(CH2)2NH(CH2)2NH2}](BPh4) in a low
      isolated yield. In contrast, the neutral complexes [ReO{pz*(CH2)2NH-Gly-CH2S}]
      (pz*=pz, 3,5-Me2pz, 4-(EtOOCCH2)-3,5-Me2pz) were synthesized almost
      quantitatively by reacting [ReOCl3(PPh3)2] or (NBu4)[ReOCl4] with the trityl
      protected chelators. The X-ray diffraction analysis of and confirmed the
      tetradentate coordination mode of the respective ancillary ligands. In the
      monoanionic chelator coordinates to the metal through four nitrogen atoms, while
      in the chelator is trianionic, coordinating to the metal through three nitrogens
      and one sulfur atom. Solution NMR studies of , including two-dimensional NMR
      techniques (1H COSY and 1H/13C HSQC), confirmed that the N3S coordination mode of
      the chelators is retained in solution. Unlike , complexes may be considered
      relevant in the development of radiopharmaceuticals, as further corroborated by
      the synthesis of the congener [99mTcO{pz(CH2)2-NH-Gly-CH2S}]. This radioactive
      compound was obtained from 99mTcO4- in aqueous medium, in almost quantitative
      yield and with high specific activity and radiochemical purity.

PMID- 17225901
TI  - Preparation and coordinating properties of {CH2(o-C6H4CH2SbMe2)}2, a novel wide
      angle cis-chelating distibine.
AB  - The unique wide-angle distibine, {CH2(o-C6H4CH2SbMe2)}2, has been prepared
      indirectly by reaction of Me2SbCl with the di-Grignard formed unexpectedly by
      coupling of o-C6H4(CH2MgCl)2 in concentrated thf solution, and directly by
      treatment of the {CH2(o-C6H4CH2MgCl)}2 with Me2SbCl. The very oxygen-sensitive
      distibine has been characterised by 1H and 13C{1H} NMR spectroscopy and high
      resolution EIMS. Oxidation of with Br2 gives the air-stable tetrabromide {CH2(o
      C6H4CH2SbMe2Br2)}2. Surprisingly, shows a very strong tendency to function as a
      cis-chelate, e.g. to Pt(IV) in the complex [PtMe3I], forming an 11-membered ring
      and providing a stable Pt(IV) stibine complex, the crystal structure of which
      shows the Sb-Pt-Sb angle to be 95.96(1) degrees. The yellow Pt(II) complex
      [PtCl2] is obtained from reaction of [PtCl2(MeCN)2] with and IR spectroscopic
      data and a crystal structure determination confirm the Cl ligands are mutually
      cis in this species. Reaction of [W(CO)4(piperidine)2] with in refluxing EtOH
      gives [W(CO)4], the IR spectrum of which shows four nu(CO) bands, also consistent
      with cis-Sb2 coordination. The cis-chelation is also confirmed by single-crystal
      X-ray structure determinations of two polymorphs of [W(CO)4].

PMID- 17225903
TI  - Tetraalkylphosphonium polyoxometalates: electroactive, "task-specific" ionic
      liquids.
AB  - The pairing of selected polyoxometalate (POM) anions with appropriate
      tetraalkylphosphonium cations is shown to yield an original family of ionic
      liquids, among them an ambient-temperature "liquid POM".

PMID- 17225904
TI  - A high-spin molecular wheel from self-assembled 'Mn rods'.
AB  - A Mn(16) wheel-like molecule made from the self-assembly of Mn "rods" in alcohol
      displays an S = 14 spin ground state and slow magnetisation relaxation consistent
      with single-molecule magnetism behaviour.

PMID- 17225902
TI  - Structure-reactivity relationships in SHOP-type complexes: tunable catalysts for
      the oligomerisation and polymerisation of ethylene.
AB  - For over 30 years complexes with the general formula [NiPh(P,O)L] (L = tertiary
      phosphine; P,O = chelating phosphanylenolato ligand) have been used as highly
      efficient oligomerisation catalysts suitable for the production of linear alpha
      olefins. The same complexes, which are usually referred to as SHOP-type catalysts
      (SHOP = Shell Higher Olefin Process) can also be used as ethylene polymerisation
      catalysts, provided they are treated with a phosphine scavenger that selectively
      removes the tertiary phosphine ligand (L). This Perspective examines the impact
      of various parameters (influence of the substituents, backbone size, solvent, use
      of co-catalysts, etc.) on the catalytic outcome of the complexes. Overall, this
      review shows that the selectivity and activity of the catalyst may be tuned
      efficiently through directed modification of the P,O chelator.

PMID- 17225905
TI  - Thermodynamic study of lanthanide(III) complexes with bifunctional monophosphinic
      acid analogues of H4dota and comparative kinetic study of yttrium(III) complexes.
AB  - New bifunctional H(4)dota-like ligands with three acetic acid and one phosphinic
      acid pendant arms and propionate (H(5)do3ap(PrA)) or 4-aminobenzyl
      (H(4)do3ap(ABn)) reactive groups bound to the phosphorus atom were investigated.
      Potentiometric studies showed that the ligands have a similar basicity to the
      parent H(4)dota and the stability constants of their complexes with sodium(i) and
      selected lanthanide(III) ions are also similar. Formation and acid-assisted
      decomplexation kinetics of yttrium(III) complexes with a series of H(4)dota-like
      ligands (H(4)dota and its phosphinic/phosphonic acid analogues) were studied and
      the reactions are sensitive to a slight modification of the ligand structure. The
      (2-carboxyethyl)phosphinic acid derivative H(5)do3ap(PrA) and the phosphonic acid
      ligand H(5)do3ap form complexes faster than H(4)dota. The most kinetically inert
      complex is that with H(4)do3ap(ABn). Rates of complexation and decomplexation can
      depend on the ability to transfer proton(s) outside/inside the complex cavity
      and, therefore, on the hydrophobicity of the ligands. The results demonstrate
      that the new bifunctional ligands are suitable for labelling biomolecules with
      yttrium(iii) radioisotopes for utilization in nuclear medicine.

PMID- 17225906
TI  - Synthesis, structure and reactivity of cuboidal-type cluster aqua complexes with
      W3PdS4 4+ core.
AB  - The reaction of PdCl(2) with [W3S4(H2O)9]4+ in the presence of hypophosphorous
      acid in 2 M HCl gives cuboidal cluster [W3(PdCl)S4(H2O)9]3+ (1) which undergoes
      condensation and crystallises from Hpts solutions as edge-linked double cubane
      cluster [{W3PdS4(H2O)9}2](pts)(8).19H2O (pts = p-toluenesulfonate) (1'). The
      substitution of Cl- in (1) by different ligands was explored. The Pd atom in the
      cluster shows an exceptionally high reactivity in the isomerisation of the
      hydrophosphoryl H2P(O)(OH), HP(O)(OH)2, HPPh(O)(OH) and HPPh2(O) molecules into
      the corresponding hydroxo tautomers HP(OH)2, P(OH)3, PhP(OH)2 and Ph2P(OH)
      stabilised by coordination at Pd. The reactions were followed by UV-Vis
      spectrophotometry and 31P NMR. Formation constants of the 1 : 1 coordination of
      [M3(PdCl)S4(H2O)9]3+ (M = Mo, W) with HP(OH)2 and As(OH)3 were obtained. The
      structures of cucurbit[6]uril (C36H36N24O12, CUC[6]) adducts
      [W3(PdP(OH)3)S4(H2O)8Cl]-(C36H36N24O12)Cl3.12.5H2O (2), and
      [W3Pd(PhP(OH)2)S4(H2O)7Cl2]2(C36H36N24O12)Cl4.9H2O (3) were determined by single
      crystal X-ray diffraction.

PMID- 17225907
TI  - Self-assembly of the unique heterotrimetallic Cu/Co/M complexes possessing
      triangular antiferromagnetic {Cu2CoPb}2 and linear ferromagnetic {Cu2CoCd2}
      cores.
AB  - Two novel heterotrimetallic octa-[Cu2CoPbCl4(L)4]2 (1) and pentanuclear
      [Cu2CoCd2Cl6(L)4(HOMe)2] (2) complexes have been prepared in one-pot reactions of
      zerovalent copper with metal chlorides in a methanol (for 1) or acetonitrile (for
      2) solution of 2-(dimethylamino)ethanol (HL) in open air. The crystal structures
      of both compounds consist of discrete centrosymmetric heterotrimetallic molecules
      revealing triangular (1) and unique consecutive (2) arrangements of magnetic
      CuII(2)CoII cores. The complex 1 can be viewed as a dimer made up of tetranuclear
      Cu2CoPbCl4(L)4 units linked through the two micro(2)-Cl atoms. The molecular
      structure of 2 is a pentanuclear assembly containing the previously unknown
      Cu(micro-O)(2)Co(micro-O)(2)Cu core. The magnetic studies of 1 revealed an
      antiferromagnetic coupling (J(CoCu) = 37 cm(-1) and J(CuCu) = 87 cm(-1)) while 2
      exhibits a weak ferromagnetic behavior (J(CoCu) = -3.2 cm(-1) and J(CuCu) = -14.2
      cm(-1)). The correlations between magnetic behaviour and structures as well as
      synthetic features are also discussed.

PMID- 17225908
TI  - Arranging up to six ferrocene carboxamides around metal centres.
AB  - Ferrocene carboxamide, FcCONH(2), forms homo- and heteroleptic complexes with
      Co(II), Ni(II) and Cu(II) via coordination of its carbonyl group. Whereas for
      both Co(II) and Ni(II), hexaferrocenyl complexes are obtained in the presence of
      BF(4)(-) anion, in the case of Cu(II) a tetraferrocenyl species is observed in
      the presence of triflate anion.

PMID- 17225909
TI  - Substitution and derivatization reactions of a water soluble iron(II) complex
      containing a self-assembled tetradentate phosphine ligand.
AB  - Facile substitution reactions of the two water ligands in the hydrophilic
      tetradentate phosphine complex cis
      [Fe{(HOCH2)P{CH2N(CH2P(CH2OH)2)CH2}2P(CH2OH)}(H2O)2](SO4) (abbreviated to
      [Fe(L1)(H2O)2](SO4), 1) take place upon addition of Cl-, NCS-, N3(-), CO3(2-) and
      CO to give [Fe(L1)X2] (2, X = Cl; 4, X = NCS; 5, X=N3), [Fe(L1)(kappa2-O(2)CO)],
      6 and [Fe(L1)(CO)2](SO4), 7. The unsymmetrical mono-substituted intermediates
      [Fe(L1)(H2O)(CO)](SO(4)) and [Fe(L(1))(CO)(kappa(1)-OSO(3))] (8/9) have been
      identified spectroscopically en-route to 7. Treatment of 1 with acetic anhydride
      affords the acylated derivative
      [Fe{(AcOCH2)P{CH2N(CH2P(CH2OAc)2)CH2}2P(CH2OAc)}(kappa2-O(2)SO2)] (abbreviated to
      [Fe(L2)(kappa2-O(2)SO2)], 10), which has increased solubility over 1 in both
      organic solvents and water. Treatment of 1 with glycine does not lead to
      functionalisation of L1, but substitution of the aqua ligands occurs to form
      [Fe(L(1))(NH(2)CH(2)CO(2)-kappa(2)N,O)](HSO(4)), 11. Compound 10 reacts with
      chloride to form [Fe(L(2))Cl(2)] 12, and 12 reacts with CO in the presence of
      NaBPh4 to form [Fe(L2)Cl(CO)](BPh4) 13b. Both of the chlorides in 12 are
      substituted on reaction with NCS- and N3(-) to form [Fe(L2)(NCS)2] 14 and
      [Fe(L2)(N3)2] 15, respectively. Complexes 2.H2O, 4.2H2O, 5.0.812H2O, 6.1.7H2O,
      7.H2O, 10.1.3CH3C(O)CH3, 12 and 15.0.5H2O have all been crystallographically
      characterised.

PMID- 17225910
TI  - Unusual interaction of alkynes with nine-vertex arachno-monocarbaboranes 4-CB8H14
      and [4-CB8H13]-.
AB  - Alkynes R(1)R(2)C(2) react with the neutral monocarbaborane arachno-4-CB(8)H(14)
      (1) at elevated temperatures (115-120 degrees C) under the formation of the
      derivatives of the ten-vertex dicarbaborane nido-5,6-C(2)B(8)H(12) (2) of general
      formula 9-Me-5,6-R1,R2-nido-5,6-C(2)B(8)H(9) (where R1,R2 = H,H 2a; Me,Me 2b;
      Et,Et 2c, H,Ph 2d, and Ph,Ph 2e) in moderate yields (26-52%). Side reaction with
      PhC(2)H also yields 1-Ph-6-Me-closo-1,2-C(2)B(8)H(8) (3d). In contrast, the
      reaction between [arachno-4-CB(8)H(13)](-) anion ((-)) and PhC(2)H produces a
      mixture of the closo anions [1-CB7H8]- (4-) and [1-CB6H7]- (5-) (yields 32 and
      24%, respectively). Individual compounds were isolated and purified by liquid
      chromatography and characterized by NMR spectroscopy ((11)B, (1)H and (13)C)
      combined with two-dimensional [(11)B-(11)B]-COSY and (1)H-{(11)B(selective)}NMR
      techniques.

PMID- 17225911
TI  - Synthesis and structures of selected benzamidinates of Li, Na, Al, Zr and Sn(II)
      using the C1-symmetric ligands [N(SiMe3)C(C6H4Me-4 or Ph)NPh]-.
AB  - Several compounds based on the C(1)-symmetric ligands [N(R)C(Ar)NPh]-
      [abbreviated as B1 (Ar = C(6)H(4)Me-4) or B2 (Ar = Ph), R = SiMe(3)] are
      reported. They are the crystalline metal benzamidinates [Li(mu:kappa2
      B1)(OEt2)](2) (1), [Al(kappa2-B1)2Me] (2), [Al(kappa2-B1)2X] [X = Cl/Me, 1 : 1
      (3)], [Sn(kappa2-B1)2] (4), Zr(kappa2-B1)2Cl2 (5), [Zr(kappa2-B1)3Cl] (6),
      [Na(mu:kappa2-B1)(tmeda)]2 (7), K[B1] (8), Li(B2)(OEt2) (9) and Zr(kappa2-B1)3Cl
      (10) and the known benzamidine Z-H2NC(C6H4Me-4) = NPh (11). They were prepared by
      (i) insertion of the nitrile 4-MeC6H4CN (1, 7, 8, 11) or PhCN (9) into the
      appropriate M-N(R')Ph [R' = R and M = Li (1, 9), Na (7), K (8)] bond and
      subsequent hydrolysis for 11 [R' = H and M = Li], or (ii) a ligand transfer
      reaction using the lithium amidinate 1 and Al(Me)2Cl (2, 3), SnCl2 (4) or ZrCl4
      (5, 6), or Li(B2) and ZrCl4 (10). The X-ray structures of 1, 2, 3, 4, 6b
      (i.e..3PhMe) 7, and 11 are presented. Exploratory polymerisation experiments are
      described, using 2, 5 or 6 as a procatalyst with methylaluminoxane (MAO) (Al : Zr
      ca. 500 : 1) as promoter. Thus toluene solutions were exposed to C2H4 under
      ambient conditions; while 2 was unresponsive, 5 and 6 showed modest activity in
      the formation of polyethylene.

PMID- 17225913
TI  - On understanding the power of judgement in percutaneous coronary intervention.
AB  - AIM: Explain how research can advance the state-of the- practice in percutaneous
      coronary intervention (PCI). METHODS AND RESULTS: Identifying the success factors
      of PCI; identifying decision- making performance (power of judgement) as the
      factor that could be advanced faster than is currently the case; explaining why
      and how such advancement needs a different research approach than those currently
      pursued in medical research; presenting initial results of this approach in the
      form of a set of basic concepts (pivoting around risk) that are useful for
      describing the decision-making process during a PCI. CONCLUSION: Building a
      terminology (ontology) of PCI decision-making concepts and then eliciting expert
      knowledge about the decision-making process itself are promising ways of
      advancing the teachability of PCI and hence the state-of-the practice.

PMID- 17225915
TI  - Loffler endocarditis without peripheral eosinophilia.

PMID- 17225914
TI  - Efficacy of extracorporeal membrane oxygenation in a congenital heart surgery
      program.
AB  - BACKGROUND: To report our experience with extracorporeal membrane oxygenation
      (ECMO) in a congenital heart surgery program. METHODS: Since 12/1996, 24 patients
      (8 newborns, 9 infants, 3 children, 4 adolescents/ adults 17-23 years), mean age
      4.0+/-7.4 years (2 days-23 years), body weight 2.7-87 kg had ECMO as circulatory
      support. Indication was failure to wean from cardiopulmonary bypass in the
      majority of cases. RESULTS: Mean duration of support was 3.8+/-2.9 d (12 h-13 d).
      Fourteen patients were weaned from ECMO (9 discharged), three successfully
      transplanted (one after switching to a pulsatile assist device). One patient on
      left-ventricular support required ECMO for sudden right ventricular failure
      (decreased). There were six deaths on ECMO due to multiorgan failure (MOV) (3) or
      no myocardial recovery (3). Six patients died after weaning (3 MOV, 2 myocardial
      failure, 1 fungal sepsis). Overall, twelve patients (50%) were discharged and are
      clinically well after 3.4+/-2.4 years (0.8-7.2 years). CONCLUSION: In our series,
      ECMO markedly reduces mortality in patients who would otherwise not survive
      either open heart surgery or myocardial failure of any origin and was not
      associated with discernible morbidity in the midterm.

PMID- 17225916
TI  - Stereolithographic reproduction of complex cardiac morphology based on high
      spatial resolution imaging.
AB  - BACKGROUND: Precise knowledge of cardiac anatomy is mandatory for diagnosis and
      treatment of congenital heart disease. Modern imaging techniques allow high
      resolution three-dimensional (3D) imaging of the heart and great vessels. In this
      study stereolithography was evaluated for 3D reconstructions of multidetector
      computed tomography (MDCT) and magnetic resonance imaging (MRI) data. METHODS: A
      plastinated heart specimen was scanned with MDCT and after segmentation a
      stereolithographic (STL) model was produced with laser sinter technique. After
      scanning the STL model with MDCT these data were compared with those of the
      original specimen after rigid registration using the iterative closest points
      algorithm (ICP). The two surfaces of the original specimen and STL model were
      matched and the symmetric mean distance was calculated. Additionally, the heart
      and great vessels of patients (age range 41 days-21 years) with congenital heart
      anomalies were imaged with MDCT (n=2) or free breathing steady, state free
      precession MRI (n=3). STL models were produced from these datasets and the
      cardiac segments were analyzed by two independent observers. RESULTS: All cardiac
      structures of the heart specimen were reconstructed as a STL model within sub
      millimeter resolution (mean surface distance 0.27+/-0.76 mm). Cardiac segments of
      the STL patient models were correctly analyzed by two independent observers
      compared to the original 3D datasets, echocardiography (n=5), x-ray angiography
      (n=5), and surgery (n=4). CONCLUSIONS: High resolution MDCT or MRI 3D datasets
      can be accurately reconstructed using laser sinter technique. Teaching, research
      and preoperative planning may be facilitated in the future using this technique.

PMID- 17225917
TI  - Two rare cases of left and right atrial congenital heart disease: cor triatriatum
      dexter and sinister.

PMID- 17225918
TI  - Plant stanol esters in low-fat milk products lower serum total and LDL
      cholesterol.
AB  - BACKGROUND: Oil-based matrices enriched with plant stanol esters lower serum LDL
      cholesterol. The effects of low-fat milk products have been less thoroughly
      examined. AIM OF THE STUDY: To evaluate the effect of three less explored low-fat
      milk products enriched with plant stanol esters on serum lipid concentrations in
      subjects with mild or moderate hypercholesterolemia. METHODS: A meta-analysis of
      four unpublished sub-studies (yoghurt, yoghurt single-shot drink: Studies I and
      II, or milk). All the substudies were randomized, placebo-controlled, double
      blind and had a parallel-group design. They were carried out in order to evaluate
      the effect of low-fat milk products enriched with plant stanol esters on serum
      lipid concentration. Each stanol-ester-enriched milk product provided 2 g of
      stanols per day, and in each study the intervention period was 5 weeks. A total
      of 199 hypercholesterolemic subjects completed the studies. RESULTS: The pooled
      treatment difference in total cholesterol was -3.8% (95% CI -6.0 to -1.7, p <
      0.001) when stanol was compared to placebo. In LDL cholesterol, the pooled
      treatment difference was -4.9% (95% CI -7.8 to -1.8, p = 0.002). There were no
      significant differences between the groups in pooled HDL cholesterol or
      triacylglycerol concentrations. The results tended to be more pronounced when we
      were certain that the yoghurt single-shot drink was ingested with lunch, and when
      the baseline LDL-cholesterol concentration was > or = 3.5 mmol/l. CONCLUSIONS:
      These results imply that low-fat milk products enriched with plant stanol esters
      lower both total cholesterol and LDL cholesterol statistically significantly in
      subjects with mild or moderate hypercholesterolemia. The changes tended to relate
      to the baseline LDL-cholesterol concentration.

PMID- 17225919
TI  - Fish oil significantly alters fatty acid profiles in various lipid fractions but
      not atherogenesis in apo E-KO mice.
AB  - BACKGROUND: Consumption of fish oil and n-3 fatty acids is associated with
      beneficial modifications in plasma lipid levels. The impact of these
      modifications on development of atherosclerotic lesions merits further
      investigation. AIM OF THE STUDY: The aim of this study was to investigate the
      impact of fish oil consumption on quality and quantity of lipoprotein fatty acids
      and its influence on atherosclerosis in apolipoprotein E-knockout (apo E-KO)
      mice. METHODS: Male apo E-KO mice were treated with 1% dietary fish oil for 14
      weeks. Plasma triglycerides (TG), phospholipids, (PL) and cholesteryl ester (CE)
      fractions were separated using thin layer chromatography. Plasma-free fatty acids
      (FFA) plus fatty acid contents of TG, PL, CE were determined using gas
      chromatography. Aortic atherosclerosis was assessed by histological and
      morphometrical techniques. RESULTS: Twenty-eight fatty acids were identified in
      each of the four lipid compartments. High amounts of n-3 fatty acids
      (eicosapentaenoic (EPA), docosahexaenoic (DHA)) were found in all of these
      fractions. The levels of EPA and DHA increased by 400 and 150%, respectively, in
      FFA, TG and PL compartments; higher increases (>500 and 200%) in EPA and DHA were
      found in CE. This markedly decreased the n-6/n-3 ratios in FFA, TG, PL, and CE by
      60, 72, 53, and 61%, respectively. These changes were accompanied by a
      significant increase in plasma triglyceride levels. Surprisingly, these changes
      did not affect atherogenesis. CONCLUSIONS: Elevated levels of EPA and DHA do not
      appear to prevent development of atherosclerotic plaques in this model. Longer
      studies warrant investigation of the direct benefits of these fatty acids against
      myocardial damage as clinical consequences of advanced atherosclerosis.

PMID- 17225920
TI  - Improved iron bioavailability in an oat-based beverage: the combined effect of
      citric acid addition, dephytinization and iron supplementation.
AB  - BACKGROUND: Iron deficiency in children is a major worldwide nutritional problem.
      An oat beverage was developed for 1- to 3-year-old children and different
      treatments were used to improve the iron bioavailability. AIM OF THE STUDY: To
      investigate the effects of citric acid addition, phytase treatment and
      supplementation with different iron compounds on non-heme iron absorption in
      human from a mineral-supplemented oat-based beverage. METHODS: A 240 g portion of
      a 55Fe-labeled test product (T) or a 59Fe-labeled reference dose (R) was served
      as breakfast after overnight fasting on four consecutive days in the order of
      TRRT. On day 18 the retention of 59Fe was measured by a whole-body counter and
      the erythrocytes uptake of 55Fe and 59Fe by a liquid-scintillation counter. Forty
      two healthy subjects (men and women) were randomized into four study groups,
      members of each being given one of the studied four products (A, B, C, and D)
      supplemented with Fe (1.3 mg/portion), Zn, Ca, Se and P. Ferric ammonium citrate
      (FeAC) was added to products A, B, and C and ferric pyrophosphate (FePP) to
      product D. Citric acid (60 mg/portion) was added to products B, C, and D and
      phytase treatment applied to products C and D. RESULTS: Citric acid improved iron
      absorption by 54% from 3.9% in product A to 6.0% in product B (p = 0.051).
      Phytase treatment increased iron absorption by 78% (from 6.0 to 10.7%, p = 0.003)
      by reducing the phytate-phosphorus content per portion from 16.3 mg in product B
      to 2.8 mg in product C. The two compounds gave similar iron absorption rates (p =
      0.916). CONCLUSIONS: A combination of citric acid addition, dephytinization and
      iron supplementation significantly increased the iron absorption in an oat-based
      beverage. Such a beverage can be useful in the prevention of iron deficiency in 1
      to 3-year-old children.

PMID- 17225921
TI  - Vitamin C promotes human endothelial cell growth via the ERK-signaling pathway.
AB  - BACKGROUND: Epidemiological, secondary prevention and small interventional trials
      suggest a preventive role of vitamin C for cardiovascular diseases (CAD),
      especially through improving endothelial dysfunction. Large primary prevention
      trials failed to confirm this. Mechanistic studies may contribute to resolve this
      discrepancy. AIM OF THE STUDY: We examined whether vitamin C activates mitogen
      activated protein kinases (MAPK) in human umbilical cord venous endothelial cells
      (HUVECs) and whether reactive oxygen species (ROS) play a role in this process.
      METHODS: Subconfluent quiescent HUVECs were incubated with vitamin C alone or in
      combination with catalase (CAT) and/or hydrogenperoxide (H2O2). Intracellular
      MAPK were determined by Western blot, proliferation by cell count and DNA
      synthesis by [3H]-thymidine-uptake. RESULTS: HUVECs were incubated with vitamin C
      (60 microM) for 5-60 min or for 20 min (30-90 microM). A dose-dependent
      phosphorylation of extracellular signal-regulated-kinases (ERKs)-1 and -2 with a
      maximum of phosphorylation at 15-20 min was observed and inhibitable by MEK1/2
      inhibitor U0126 (5-10 microM). Vitamin C (60 microM) stimulated phosphorylation
      of ERK5, but not of p38 and c-Jun, demonstrating a different MAPK-activation
      pattern compared to H2O2. Vitamin C (60 microM) induced proliferation and a dose
      dependent [3H]-thymidine-uptake (30-120 microM) within 20 h. CAT (0.3 U/ml) did
      neither suppress the vitamin C induced [3H]-thymidine-uptake nor ERK1/2
      phosphorylation. CAT (0.3 U/ml), but not vitamin C (60 microM) abrogated the
      inhibitory effects of H2O2 (100 microM) on [3H]-thymidine-uptake. CONCLUSION:
      Physiological vitamin C-concentrations promote proliferation of subconfluent ECs
      by activating an ERK1/2 controlled pathway. Targeting MAPK by vitamin C may
      improve, besides antioxidant mechanisms, endothelial dysfunction by promoting a
      fast regeneration of the endothelium after tissue injury, particularly required
      during secondary prevention and early development.

PMID- 17225923
TI  - A 30-year result of deforming arthritis in systemic lupus erythematosus.
AB  - Symmetric non-erosive polyarthritis is the most common clinical feature in
      systemic lupus erythematosus (SLE). We report on a 42-year follow-up of a 71-year
      old woman who first had polyarthritis in 1963 at the age of 29 and continuously
      since 1975. SLE was diagnosed in 2000 at the age of 66 as anti-dsDNA (56 kIU/l),
      and antinuclear antibodies (1:2,560) turned positive. In 2005 hand and feet
      radiographs revealed severe Jaccoud's arthritis with subluxations but without
      erosions.

PMID- 17225922
TI  - Solubility, uptake and biocompatibility of lutein and zeaxanthin delivered to
      cultured human retinal pigment epithelial cells in tween40 micelles.
AB  - Carotenoids lutein and zeaxanthin are proposed to protect ocular tissues from
      free-radical damage that can cause cataract and age-related macular degeneration
      (AMD). They accumulate selectively in the lens and macular region of the retina.
      Changes in the retinal pigment epithelium are characteristic in AMD. Efficient
      uptake is essential to study the intracellular effects of carotenoids in cell
      cultures. For in vitro experiments carotenoids are often dissolved in organic
      solvents like tetrahydrofuran (THF), dimethylsulfoxide (DMSO) and n-hexane, but
      difficulties have been associated with these application methods. Recently,
      O'Sullivan et al. (SM O'Sullivan et al., Br J Nutr 91 (2004) 757) developed a
      method whereby carotenoids could be delivered to cultured cells without the
      cytotoxic side effects often observed when organic solvents are used. We modified
      this method and investigated the effects of different carotenoid-formulations
      (ethanol/Tween40, methanol/tween40 and acetone/Tween40) on the uptake of lutein
      and zeaxanthin by differentiated ARPE-19 cells, cell viability and the expression
      of the "stress" gene HO-1, which is easily induced by a range of stimuli
      including chemical and physical agents. Micelle formulations prepared with
      ethanol/Tween40 resulted in the lowest LDH release, the highest carotenoid uptake
      and the lowest stress response (changes in HO-1 mRNA expression).

PMID- 17225924
TI  - Serum proinflammatory cytokines directing T helper 1 polarization in patients
      with familial Mediterranean fever.
AB  - Th1 type polarization has been implicated in the pathogenesis of familial
      Mediterranean fever (FMF). Interleukin-12 (IL-12) and IL-10 are proinflammatory
      cytokines, which play crucial role in Th1 and Th2 type immune response,
      respectively. IL-18 has a dual effect on T cell response: it was recognized as an
      IFN-gamma-inducing factor in T cells; acting in synergy with IL-12, leading to
      the development of Th1 type immune responses. But, in the absence of IL-12, IL-18
      can promote the production of Th2 cytokines and take part in allergic
      inflammation. The aim of this study is to measure serum levels of IL-10, IL-12,
      and IL-18 in patients with FMF, and to investigate the relationship of their
      expressions with FMF attacks. Serum IL-10, IL-12, and IL-18 levels from patients
      with FMF were investigated. Thirty-one FMF patients with attack-free, 24 FMF
      patients with attack and 20 healthy controls were enrolled in the study. The
      levels of IL-10, IL-12p70 and IL-18 were measured by ELISA. Serum IL-10 levels
      were not different in FMF patients with attack and attack-free, and healthy
      controls. Serum IL-12 levels in FMF patients both with attack and attack-free
      were significantly higher than healthy controls (P = 0.002 and P = 0.047,
      respectively). There were no differences between FMF patients with attack and
      attack-free with regard to serum IL-12 levels. Serum IL-18 levels in FMF patients
      with attack and attack-free were significantly higher than healthy controls (P <
      0.001 for both groups). With respect to serum IL-18 levels, no difference was
      found between FMF patients with attack and attack-free. Our results suggest that
      IL-12 and IL-18 contribute to the establishment of Th1 polarization seen in FMF
      and play a part in its pathogenesis. Detection of increased levels of IL-12 and
      IL-18 in patients with inactive disease implies that they seem to assist Th1
      activation and subclinical inflammation persisting during the attack-free period
      of the disease.

PMID- 17225925
TI  - The CTLA-4 -1661A/G and -1772T/C dimorphisms in Japanese patients with systemic
      sclerosis.

PMID- 17225927
TI  - Chitinase gene diversity at a deep sea station of the east Pacific nodule
      province.
AB  - The Pacific nodule province covered about 4.5 million km(2) in the east tropical
      Pacific with an abundance of polymetallic nodules at the seafloor. In view of the
      environmental protection and resource preservation, the survey of biodiversity
      was important during the reconnaissance and exploitation in this area. As one of
      the important component of the deep sea ecosystem, the microbial community in the
      Pacific nodule province was still largely unknown. The chitinolytic bacteria
      diversity in deep-sea sediment of a station within the Pacific nodule province
      was examined by molecular technology. A total of 18 chitinase genes were detected
      by a set of degenerate PCR primer specific for chiA gene fragment of family 18
      chitinase. Most of them belonged to the Serratia-like chitinase. Eight genes had
      different amino acid sequences in the conserved motif, encompassing the catalytic
      site among the ChiA protein of family 18 glycosyl hydrolases, and clustered in an
      independent clade on the phylygenetic tree.

PMID- 17225926
TI  - Prokaryotic lifestyles in deep sea habitats.
AB  - Gradients of physicochemical factors influence the growth and survival of life in
      deep-sea environments. Insights into the characteristics of deep marine
      prokaryotes has greatly benefited from recent progress in whole genome and
      metagenome sequence analyses. Here we review the current state-of-the-art of deep
      sea microbial genomics. Ongoing and future genome-enabled studies will allow for
      a better understanding of deep-sea evolution, physiology, biochemistry, community
      structure and nutrient cycling.

PMID- 17225928
TI  - Safety of etanercept therapy in rheumatoid patients undergoing surgery:
      preliminary report.
AB  - This is a preliminary report on a case-series of rheumatoid patients that
      underwent various kinds of elective surgery but did not withdraw etanercept
      therapy in spite of physician advise. Elective surgery consisted of right knee
      surgical prosthesis, bilateral cataract, bilateral hallux valgus, right hip
      prosthesis, bladder stone by cystoscopy and left inguinal hernia. All the
      patients had a regular healing rate. During follow-up (6-12 months) no one of
      these patients were suffering from infective complications after surgery.
      According to same recent literature results, our data suggest that it is the time
      to value rheumatoid patient preferences through a correct information about cost
      benefit of this treatment to establish together with patients if etanercept
      therapy has to be discontinued before and after elective surgery. Finally, we
      think that adverse drug reaction surveillance has to be boosted, and editors of
      leading scientific journal should publish more papers on case-series about drug
      safety and tolerability in particular conditions.

PMID- 17225929
TI  - Long-standing refractory polymyositis responding to mycophenolate mofetil: a case
      report and review of the literature.
AB  - The authors describe a young patient affected by long-standing polymyositis
      refractory to conventional treatment who showed a rapid and striking response to
      mycophenolate mofetil treatment.

PMID- 17225934
TI  - TonB-dependent energy transduction between outer and cytoplasmic membranes.
AB  - The TonB system of Escherichia coli (and most other Gram-negative bacteria) is
      distinguished by its importance to iron acquisition, its contribution to
      bacterial pathogenesis, and a unique and mysterious mechanism of action. This
      system somehow gathers the potential energy of the cytoplasmic membrane (CM)
      proton gradient and delivers it to active transporters in the outer membrane
      (OM). Our understanding of this system is confounded by the challenge of
      reconciling often contradictory in vivo and in vitro studies that are presented
      in this review.

PMID- 17225930
TI  - Xenograft use in reconstructive pelvic surgery: a review of the literature.
AB  - Xenografts, bovine or porcine acellular collagen bioprostheses derived from
      dermis, pericardium, or small-intestine submucosa, were introduced to overcome
      synthetic mesh-related complications. Although there are eight commercially
      available xenografts, there is a paucity of empiric information to justify their
      use instead of the use of synthetic grafts. In addition, limited data are
      available about which graft characteristics are important and whether graft
      reinforced repairs reduce recurrences and improve outcomes. To address these
      knowledge gaps, we conducted a Medline search of published reports on xenografts
      in animal and human trials. Histologic host response to implanted xenograft
      material depends primarily on chemical cross-linking and porosity, and it is
      limited to four responses: resorption, incorporation, encapsulation, and mixed.
      No clinical data unequivocally demonstrate an improved benefit to graft
      reinforced repair.

PMID- 17225931
TI  - Association of vascular parkinsonism with impaired neuronal integrity in the
      striatum.
AB  - The purpose of this study is to identify the underlying differences between
      patients with white matter lesions (WMLs) who manifested gait disturbance
      suggestive of vascular parkinsonism (VaP) and those who did not, using the PET
      scan. Fourteen patients with extensive WMLs, as determined by MRI, were divided
      into two groups - 7 with gait disturbance and 7 without it. Neuronal integrity
      was evaluated with a PET scan using [(11)C]flumazenil (FMZ) by calculating the
      distribution volume of FMZ (FMZ-V(d)) in various regions of interest by non
      linear curve fitting. Additionally, tracer kinetic analysis was applied for voxel
      by-voxel quantification of FMZ-V(d) and data analysis was performed using
      statistical parametric mapping. The striatal FMZ-V(d) values were inversely
      correlated with the motor UPDRS scores (r = 0.70, p < 0.005), and their
      reductions were associated with the presence of gait disturbance. Therefore,
      differences in neuronal integrity in the striatum may determine whether patients
      with WMLs develop VaP or not.

PMID- 17225935
TI  - Acute confusion in patients with systemic cancer.
AB  - OBJECTIVE: To determine the incidence, the causes and the prognostic value for
      survival of acute confusion (delirium) in patients admitted to a general cancer
      hospital. PATIENTS: Hundred consecutive patients with confusion were examined; 78
      had a metastatic disease, 11 had local tumor and 11 had no sign of tumor
      recurrence at admission. Patients with confusion represented 11.8% (95%CI: 9.7
      14.2%) of admissions. Follow-up period lasted 18 months from the inclusion of the
      last patient. RESULTS: Structural brain lesions (SBL) were mostly metastatic and
      caused confusion in 36 patients. 57 patients had a toxic or metabolic
      encephalopathy (TME). The cause remained unexplained in 6 cases, and in one
      patient the final diagnosis was psychotic state. Most patients with TME had more
      than one abnormality which could cause confusion. Confusion was reversible in 34
      patients, and the odds for its regression was 3-fold higher in patients with TME
      (P = 0.02). Survival was significantly shorter (P = 0.02) in patients with SBL
      (median: 3 weeks) than in patients with TME (median: 8 weeks). However, the
      survival was significantly longer (P = 0.007) in patients with only one toxic or
      metabolic disorder (median: 20.5 weeks) than in patients with multiple changes
      (median: 5 weeks). CONCLUSION: Confusion is common in general cancer population.
      TME is the leading etiology and it is due to multiple causes in most patients.
      SBL causes confusion in one third of the patients. Patients with TME have a
      greater chance to recover, and survive longer especially if they have only one
      toxic or metabolic change.

PMID- 17225933
TI  - Instabilities in vertically vibrated fluid-grain systems.
AB  - When a bed of fluid-immersed fine grains is exposed to vertical vibration a
      wealth of phenomena may be observed. At low frequencies a horizontal bed geometry
      is generally unstable and the bed breaks spatial symmetry, acquiring a tilt. At
      the same time it undergoes asymmetric granular convection. Fine binary mixtures
      may separate completely into layers or patterns of stripes. The separated regions
      may exhibit instabilities in which they undergo wave-like motion or exhibit quasi
      periodic oscillations. We briefly review these and a number of related
      behaviours, identifying the physical mechanisms behind each. Finally, we discuss
      the magneto-vibratory separation of binary mixtures which results from exposing
      each component to a different effective gravity and describe the influence of a
      background fluid on this process.

PMID- 17225938
TI  - Proton treatment of uveal melanomas.

PMID- 17225932
TI  - Midbrain serotonin transporter binding potential measured with [11C]DASB is
      affected by serotonin transporter genotype.
AB  - BACKGROUND: Homozygote carriers of two long (L) alleles of the serotonin
      transporter (5-HTT) regulatory region displayed in vitro a twofold increase in 5
      HTT expression compared with carriers of one or two short (S) alleles. However,
      in vivo imaging studies yielded contradictory results. Recently, an A > G
      exchange leading to differential transcriptional activation of 5-HTT mRNA in
      lymphobalstoid cell lines was discovered in the 5-HTT regulatory region. In vitro
      and in vivo evidence suggests that [(11)C]DASB, a new 5-HTT ligand offers some
      advantages over the ligands used in previous studies in measuring 5-HTT density
      independent of synaptic levels of serotonin. METHOD: We assessed 5-HTT binding
      potential (BP (2)) in the midbrain of 19 healthy subjects with positron emission
      tomography and [(11)C]DASB. Accounting for the hypothesized functional similarity
      of L (G) and S in driving 5-HTT transcription, we assessed whether L (A) L (A)
      homozygotes display increased midbrain BP (2) compared with carriers of at least
      one S allele. RESULTS: BP (2) in the midbrain was significantly increased in L
      (A) L (A) homozygotes compared with carriers of at least one S allele.
      Interestingly, the genotype effect on the midbrain was significantly different
      from that on the thalamus and the amygdala where no group differences were
      detected. CONCLUSIONS: This in vivo study provides further evidence that subjects
      homozygous for the L (A) allele display increased expression of 5-HTT in the
      midbrain, the origin of central serotonergic projections.

PMID- 17225936
TI  - Hyperdiploidy defines a distinct cytogenetic entity of meningiomas.
AB  - BACKGROUND: The most common chromosomal aberration found in meningiomas is
      monosomy 22. Progression and recurrence of meningiomas are usually associated
      with additional chromosome losses. Rarely, however, meningiomas have strongly
      hyperdiploid karyotypes with over 50 chromosomes; the objective of this study was
      to explore the cytogenetic and histopathologic patterns as well as the clinical
      significance of hyperdiploidy in meningiomas. METHODS: Within a series of 677
      consecutive meningiomas, we identified a subgroup comprising 16 cases that
      display a strikingly uniform pattern of hyperdiploidy mostly without structural
      chromosome rearrangements, as shown by banding techniques and, in the single
      structurally aberrant case, spectral karyotyping. RESULTS: These meningiomas each
      have between 50 and 56 chromosomes, with trisomy 12 (14/16 cases), trisomy 20
      (13/16 cases), trisomy 5 (12/16 cases), and trisomy 17 (10/16 cases).
      Histomorphologically, hyperdiploid meningiomas feature a heterogeneous phenotype.
      However, they are associated with a higher histological grade, and decreased
      expression of alkaline phosphatase as compared to meningiomas with typical
      karyotype. In two patients, recurrences were documented and three patients died
      of disease during the period of observation, indicating a worse prognosis of
      hyperdiploid than of cytogenetically typical meningiomas. CONCLUSION: We conclude
      that hyperdiploidy constitutes a small but clinically relevant entity of
      biologically aggressive meningiomas, which are cytogenetically distinguishable
      from the majority of common-type meningiomas.

PMID- 17225940
TI  - Radio(chemo)therapy plus resection versus radio(chemo)therapy alone for the
      treatment of stage III esophageal cancer.
AB  - PURPOSE: To compare radio(chemo)therapy with 41.4-50.4 Gy (moderate dose, MD-RCT)
      plus resection versus radio(chemo)therapy with 59.4-66.6 Gy (higher dose, HD-RCT)
      alone for outcome in stage III esophageal cancer, and to investigate potential
      prognostic factors including preradiotherapy (pre-RT) hemoglobin. PATIENTS AND
      METHODS: 148 patients with stage III esophageal cancer, treated with MD-RCT plus
      resection (n = 41) or HD-RCT alone (n = 107), were retrospectively evaluated for
      age, gender, performance status, tumor location, tumor length, stage, histology,
      grading, number of chemotherapy courses, pre-RT hemoglobin, resection, overall
      survival (OS), metastases-free survival (MFS), and locoregional control (LC).
      RESULTS: On univariate analysis, MD-RCT plus resection resulted in better 2-year
      OS (57% vs. 25%; p = 0.049), 2-year MFS (71% vs. 39%; p = 0.041), and 2-year LC
      (76% vs. 39%; p = 0.003). On multivariate analysis, results maintained
      significance for LC (p = 0.021). According to multivariate analysis, pre-RT
      hemoglobin was associated with OS (p = 0.003), MFS (p = 0.043), and LC (p =
      0.041), tumor length with OS (p = 0.002) and MFS (p = 0.017), and the number of
      chemotherapy courses with OS (p = 0.008). Complications were more frequent in the
      MD-RCT-plus-surgery group (p < 0.001). Acute (p = 0.47) and late toxicity (p =
      0.86) were similar in both groups. In patients receiving surgery, R0 resection
      was superior to R1/2 resection for OS (p < 0.001), MFS (p = 0.030), and LC (p <
      0.001). MD-RCT plus R0 resection was also superior to HD-RCT alone. CONCLUSION:
      MD-RCT plus resection resulted in better LC than HD-RCT alone. If R0 resection is
      possible, MD-RCT plus resection appears preferable, as it results in better
      outcome. If only R1/2 resection can be performed, HD-RCT alone appears preferable
      regarding outcome and the greater morbidity associated with resection.

PMID- 17225939
TI  - Radiation therapy for painful heel spurs: results of a prospective randomized
      study.
AB  - PURPOSE: To evaluate the efficacy of two different dose-fractionation schedules
      for radiation therapy (RT) in patients with painful heel spurs. PATIENTS AND
      METHODS: 130 patients were randomized into two groups: the low-dose (LD) group (n
      = 65 heels) received a total dose of 3.0 Gy given in two weekly fractions of 0.5
      Gy; in the high-dose (HD) group (n = 65 heels), two weekly fractions of 1.0 Gy
      were applied over 3 weeks (total dose 6.0 Gy). In 24 sites of the HD group and 17
      sites of the LD group, a second RT course was given. The results were assessed
      using a five-level function score which was documented before RT, at the end of
      each RT course, and at 6 weeks and 6 months thereafter. RESULTS: At 6-month
      follow-up, RT led to a highly significant reduction of symptoms in both groups.
      In the HD group, 31 sites were classified as excellent (score: 90-100), 13 as
      good (score: 70-85), twelve as moderate (score: 45-65), and nine as poor (score:
      0-40). In the LD group, 35 sites were classified as excellent, eight as good, ten
      as moderate, and twelve as poor. The comparison of the difference of the sum
      score and the single criteria before RT and at 6 months after RT using the
      Wilcoxon-Mann-Whitney U-test revealed no statistically significant difference of
      response to RT between both groups. CONCLUSION: RT is an effective treatment
      option for the management of inflammatory heel spurs. The dose for an RT course
      should not exceed 3.0 Gy.

PMID- 17225942
TI  - Postoperative radiotherapy for prostate cancer : evaluation of target motion and
      treatment techniques (intensity-modulated versus conformal radiotherapy).
AB  - PURPOSE: To determine the extent of target motion in postprostatectomy
      radiotherapy (RT) and the value of intensity-modulated radiotherapy (IMRT)
      compared to three-dimensional conformal radiotherapy (3D-CRT). PATIENTS AND
      METHODS: 20 patients underwent CT scans in supine position with both a full
      bladder (FB) and an empty bladder (EB) before RT and at three dates during the RT
      series. Displacements of the CTV (clinical target volume) center of mass and the
      posterior border were determined. 3D-CRT and IMRT treatment plans were compared
      regarding homogeneity, conformity, and dose to organs at risk. RESULTS: In the
      superior-inferior direction, larger displacements were found for EB compared to
      FB scans; anterior-posterior and right-left displacements were similar. With an
      initial rectum volume of < 115 cm(3), 90% of displacements at the posterior
      border were within a margin of 6 mm. The non-target volume irradiated in the high
      dose area doubled in 3D-CRT versus IMRT plans (80 cm(3) vs. 38 cm(3) encompassed
      by the 95% isodose). Bladder dose was significantly lower with IMRT, but no
      advantage was found for the integral rectal dose. An adequate bladder filling was
      paramount to reduce the dose to the bladder. CONCLUSION: Postprostatectomy RT can
      be recommended with FB due to an improved CTV position consistency and a lower
      dose to the bladder. With improved non-target tissue and bladder volume sparing,
      IMRT is an option for dose escalation. However, this analysis did not find an
      advantage concerning the integral rectal dose with IMRT versus 3D-CRT.

PMID- 17225943
TI  - 6-year experience of concurrent radiochemotherapy with vinorelbine plus a
      platinum compound in multimorbid or aged patients with inoperable non-small cell
      lung cancer.
AB  - BACKGROUND AND PURPOSE: Although poor-risk patients represent no minority in
      inoperable non-small cell lung cancer (NSCLC), there is little experience with
      concurrent radiochemotherapy (RCT) in this group. Here, the authors report on the
      feasibility and efficacy of RCT with vinorelbine plus carboplatin or cisplatin in
      NSCLC patients with comorbidities and poor general health or advanced age.
      PATIENTS AND METHODS: A total of 66 patients (ten women, 56 men, median age 68
      years) with inoperable NSCLC and an increased risk of treatment side effects (WHO
      performance score of 2-3; cardiac, pulmonary or renal failure or extensive weight
      loss before treatment, or an age of 71-78 years) were treated with vinorelbine
      12.5 mg/m(2) on days 1, 8, 15, 29, 36, and 43 in combination with either
      carboplatin 70 mg/m(2) (n = 59) or cisplatin 20 mg/m(2) (n = 7) on days 1-5 and
      29-33 in addition to receiving conventional fractionated radiotherapy with doses
      of up to 63 Gy (90% isodose). RESULTS: 62 of 66 patients (94%) reached the 90%
      level of the prescribed radiation dose, and 41/66 patient (62%) received at least
      two cycles of the platinum compound and four cycles of vinorelbine. The following
      hematologic side effects (CTC classification [Common Toxicity Criteria]) were
      observed: grade 3 (12%) and grade 4 (15%) thrombocytopenia, grade 3 (38%) and
      grade 4 (4%) leukocytopenia, and anemia requiring transfusion (26%). Other side
      effects (CTC) included grade 3 (3%) and grade 4 (2%) esophagitis and grade 3
      pneumonitis (3%). The response rates were as follows: complete remission 18%,
      partial remission 56%, stable disease 21%, and progressive disease 5%. The
      cumulative survival rates were 53%, 24%, and 8% at 12 months, 24 months, and 5
      years, respectively. CONCLUSION: After including a larger group of patients than
      in 2003 and following the patients for several years, the authors determine that
      concurrent RCT consisting of vinorelbine plus a platinum compound and
      conventional fractionated radiotherapy can be carried out with manageable
      toxicity, even in this negatively selected population of patients. Their survival
      rates were comparable to those achieved in other studies with simultaneous RCT.

PMID- 17225941
TI  - Radiotherapy for orbital lymphoma : outcome and late effects.
AB  - PURPOSE: To analyze the effectiveness of radiotherapy in the management of
      orbital non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: 42 patients (median
      age 64.5 years) were reviewed retrospectively. The median follow-up period was 58
      months. 26 patients had stage IE orbital lymphoma (22 indolent, four aggressive
      NHLs). 16 patients had advanced NHLs in stages II-IV with orbital involvement
      (eleven indolent, five aggressive NHLs). The median radiation dose was 40 Gy (20
      46 Gy) for indolent lymphoma and 44 Gy (20-48 Gy) for aggressive lymphoma.
      Patients with stage IE were treated with at least 30 Gy. RESULTS: The 5-year
      local control rate for patients with stage I was 100%, the 5-year overall
      survival 91%. Two distant relapses were found, but no lymphoma-related death was
      detected. The 5-year local control rate for patients in stages II, III, and IV
      was 80%. Two local failures were detected. The 5-year overall survival for the
      advanced stages was 47%, nine patients with stages III and IV died due to
      systemic progression of lymphoma. Acute, radiotherapy-related complications grade
      3/4 were not observed. Late effects grade 1/2 were documented in 45%. Six
      patients, treated with doses of > 36 Gy, developed grade 3 complications (four
      cataract, two dryness). CONCLUSION: Radiotherapy alone yields excellent local
      control and overall survival rates in orbital lymphoma stage IE. Local
      irradiation is also well tolerated and effective in advanced NHL stages with
      orbital infiltration. Doses of > 36 Gy resulted in an increase of late
      complications.

PMID- 17225945
TI  - The effect of a carbon-fiber couch on the depth-dose curves and transmission
      properties for megavoltage photon beams.
AB  - PURPOSE: To investigate the attenuation of a carbon-fiber tabletop and a
      combiboard, alongside with the depth-dose profile in a solid-water phantom.
      MATERIAL AND METHODS: Depth-dose measurements were performed with a Roos chamber
      for 6- and 10-MV beams for a typical field size (15 cm x 15 cm, SSD [source
      surface distance] 100 cm). A rigid-stem ionization chamber was used to measure
      transmission factors. RESULTS: Transmission factors varied between 93.6% and
      97.3% for the 6-MV beam, and 95.1% and 97.7% for the 10-MV photon beam. The
      lowest transmission factors were observed for the oblique gantry angle of 150
      degrees with the table-combiboard combination. The surface dose normalized to a
      depth of 5 cm increased from 59.4% (without table, 0 degrees gantry), to 108.6%
      (tabletop present, 180 degrees gantry), and further to 120% (table-combiboard
      combination) for 6-MV photon beam. For 10 MV, the increase was from 39.6%
      (without table), to 88.9% (with table), and to 105.6% (table-combiboard
      combination). For the 150 degrees angle (tablecombiboard combination), the dose
      increased from 59.4% to 120% (6 MV) and from 39% to 108.1% (10 MV). CONCLUSION:
      Transmission factors for tabletops and accessories directly interfering with the
      treatment beam should be measured and implemented into the treatment-planning
      process. The increased surface dose to the skin should be considered.

PMID- 17225944
TI  - Effects of systemic or topical administration of sodium selenite on early
      radiation effects in mouse oral mucosa.
AB  - PURPOSE: To quantify the effect of sodium selenite (selenium) on radiation
      induced oral mucositis (mouse) after subcutaneous or topical administration.
      MATERIAL AND METHODS: Mucosal ulceration of the lower epithelium of mouse tongue
      was analyzed. Selenium (5 mug) was applied subcutaneously (s.c.) or locally, 60
      min or 30 min prior to irradiation, respectively. In combination with single-dose
      irradiation, a single selenium application was given. With daily fractionated
      irradiation (3 Gy/fraction) for 1 week (days 0-4), selenium was administered at
      all 5 days of irradiation. With ten fractions over 2 weeks, selenium was applied
      in week 1, week 2, or both. All fractionation protocols were terminated by graded
      test doses to generate full dose-effect curves. RESULTS: In a single-dose control
      experiment, the ED(50) (dose after which ulcer induction is expected in 50% of
      the mice) was 12.9 +/- 1.6 Gy. Selenium increased the ED(50) to 17.7 +/- 2.6 Gy
      (s.c.; p = 0.0003) and 16.3 +/- 3.0 Gy (local; p = 0.0104). The ED(50) for test
      irradiation after 5 x 3 Gy was 7.4 +/- 2.2 Gy. Subcutaneous administration of
      selenium resulted in an ED(50) of 11.5 +/- 2.0 Gy (p = 0.0015), local application
      yielded an ED(50) of 10.0 +/- 2.1 Gy (p = 0.0284). The ED(50) for test
      irradiation after 10 x 3 Gy/2 weeks was 8.0 +/- 1.7 Gy. Subcutaneous or local
      administration of selenium in week 1 yielded a significant increase in ED(50) to
      10.5 +/- 1.0 Gy (p = 0.0069) and 10.7 +/- 1.0 Gy (p = 0.0039), respectively. By
      clear contrast, selenium administration in week 2 had no significant effect.
      Administration in both weeks resulted in an ED(50) of 9.1 +/- 2.0 Gy (s.c.; p =
      0.2747) and 9.7 +/- 1.4 Gy (local; p = 0.0541). CONCLUSION: Administration of
      sodium selenite during clinically relevant fractionated irradiation protocols has
      a significant effect during the initial treatment phase, i.e., week 1 in the
      mouse. Therefore, in clinical radiotherapy, the latent time to manifestation of
      confluent mucositis may be significantly prolonged, and hence the burden for the
      patient clearly reduced by selenium.

PMID- 17225946
TI  - Letter by M. Fitzek on Hocht S, Bechrakis NE, Nausner M, et al. Proton therapy of
      uveal melanomas in Berlin: 5 years of experience at the Hahn-Meitner Institut:
      in: Strahlenther Onkol 2004;180:419-24 (No. 7) (DOI 10.1007/s00066-004-1222-5).

PMID- 17225937
TI  - Recurrences of meningiomas: predictive value of pathological features and
      hormonal and growth factors.
AB  - OBJECTIVE: Recurrence of apparently completely resected benign meningiomas is a
      rather frequent event, the mechanisms of which are still unclear. The aim of this
      study is to define the pathological features, proliferation indexes, growth
      factors and hormone receptor expression in predicting the meningioma recurrence.
      METHODS: Two groups of 50 completely resected benign WHO I meningiomas, with and
      without recurrence respectively, have been reviewed. Tumor location, consistency,
      vascularity, and histological types have been considered. Immunohistological
      studies include mitotic index (MI), Ki-67 LI, estrogen and progesterone receptors
      (ER and PR), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor
      (EGF), and Bcl-2. All these factors have been correlated with the recurrence.
      RESULTS: The tumor recurrence was not correlated with the patient age, tumor
      location, consistency, vascularity and histology. There was not difference in the
      histological pattern between local and diffuse recurrences. M.I. and Ki-67 LI
      were significantly correlated with the recurrence (P<0.0001). PR negativity had a
      strong predictive value of recurrence (P<0.0001), whereas the ER status was not
      relevant. VEGF and EGF-R were not correlated with the recurrence of meningiomas,
      whereas the Bcl-2 protein positivity showed a tendency to the significativity
      (P=0.0294). The negative association between Bcl-2 and PR is an interesting
      finding of our study. CONCLUSIONS: Higher MI and Ki-67 LI and PR negativity are
      predictive factors of recurrence of benign (WHO I) completely resected
      meningiomas, particularly when Bcl-2 positivity is associated.

PMID- 17225948
TI  - Traumatic brain injury-mediated hypopituitarism. Report of four cases.
AB  - Hypopituitarism has been increasingly recognised following traumatic brain
      injury. We report four children involved in motor vehicle accidents who had
      traumatic brain injury-mediated hypopituitarism. Various hormone defects are
      described. Growth hormone was the most commonly affected pituitary hormone. The
      time interval between the injury and diagnosis of pituitary hormone deficiency
      was between 2.5 weeks to 1.5 years. Hormone replacement therapy permitted normal
      completion of growth and development. Awareness among physicians treating
      children with traumatic brain injury of the risk of hypopituitarism is necessary
      to optimise the outcome.

PMID- 17225949
TI  - Late-onset right-sided diaphragmatic hernia in neonates - case report and review
      of the literature.
AB  - An association between early-onset neonatal Group B streptococcal (GBS) sepsis
      and subsequent diagnosis of late-onset diaphragmatic hernia has been reported. We
      report one such case and review the literature. The index case involved a male
      preterm neonate in whom late-onset right diaphragmatic was diagnosed on day 21
      following early-onset GBS sepsis. Our literature review identified 40 cases of
      such an association. The typical description involves near term male neonates,
      who improved from an early-onset GBS sepsis only to have a secondary respiratory
      deterioration leading to the diagnosis of late-onset right diaphragmatic hernia.
      With surgical repair, this condition has an excellent survival rate. In
      conclusion, the pathophysiological mechanisms underlying the association remain
      to be elucidated. Awareness of the associated pleural effusion is important to
      avoid inadvertent organ injury due to chest drains.

PMID- 17225950
TI  - Stimulation programs for pediatric drug research--do children really benefit?
AB  - Most drugs that are currently prescribed in pediatrics have not been tested in
      children. Pediatric drug studies are stimulated in the USA by the pediatric
      exclusivity provision under the Food and Drug Administration Modernization Act
      (FDAMA) that grants patent extensions when pediatric labeling is provided. We
      investigated the effectiveness of these programs in stimulating drug research in
      children, thereby increasing the evidence for safe and effective drug use in the
      pediatric population. All drugs granted pediatric exclusivity under the FDAMA
      were analyzed by studying the relevant summaries of medical and clinical
      pharmacology reviews of the pediatric studies or, if these were unavailable, the
      labeling information as provided by the manufacturer. A systematic search of the
      literature was performed to identify drug utilization patterns in children. From
      July 1998 to August 2006, 135 drug entities were granted pediatric exclusivity.
      Most frequent drug groups were anti-depressants and mood stabilizers, ACE
      inhibitors, lipid-lowering preparations, HIV antivirals, and non-steroidal anti
      inflammatory and anti-rheumatic drugs. The distribution of the different drugs
      closely matched the distribution of these drugs over the adult market, and not
      the drug utilization by children. Many drug studies in children have been
      performed since the introduction of the FDAMA. However, children infrequently use
      the drugs granted pediatric exclusivity. The priorities for pediatric drug
      research should be set by the need of the patients, not by market considerations.

PMID- 17225951
TI  - Grommets in otitis media with effusion: the most frequent operation in children.
      But is it associated with significant complications?
AB  - INTRODUCTION: Otitis media with effusion is one of the most frequent diseases in
      children, and its management requires the attention of general practitioners,
      pediatricians and ear, nose and throat (ENT) surgeons. The main complications
      associated with tympanostomy tube insertion, are: (1) purulent otorrhea (10-26%
      of cases), in which local otic preparations might be effective, and biofilm
      resistant tubes may decrease this complication in the future; (2)
      myringosclerosis (39-65% of operated ears), with usually no serious sequelae; (3)
      segmental atrophy (16-75% of cases); (4) atrophic scars and pars flaccida
      retraction pockets (28 and 21% of operated ears, respectively); (5) tympanic
      membrane perforations (3% of cases, although with T-tubes, the incidence may be
      as high as 24%); (6) cholesteatoma (1% of cases), although tympanostomy tubes may
      sometimes prevent, rather than contribute to its development; (7) granulation
      tissue (5-40% of instances), when the duration of tube retention is prolonged.
      CONCLUSION: It would appear that the complications associated with tympanostomy
      tube insertion are more frequent than anticipated, reaching 80% of operated ears
      under specific circumstances and in certain subgroups of children. These
      complications may resolve with conservative management, but in persistent cases
      surgical removal of the tubes is mandatory.

PMID- 17225953
TI  - The role of supernova neutrinos on molecular homochirality.
AB  - Electroweak parity violating interaction between supernova (SN) neutrinos and
      electrons of a simple chiral molecule is studied related to the origin of
      molecular homochirality. Appearance of supernova remnants inside molecular clouds
      favours the interaction of SN-neutrinos with interstellar molecules, leading to a
      energetic difference between the two enantiomers of the order of 10(-5) eV. This
      energetic difference is closer to the thermic energy of the interstellar medium,
      so molecular homochirality could be enhanced in molecular clouds containing
      supernova remnants inside it due to neutrino interaction.

PMID- 17225952
TI  - Generation of secondary small interfering RNA in cell-autonomous and non-cell
      autonomous RNA silencing in tobacco.
AB  - Small interfering RNA (siRNA) species with 21-25 nucleotides in length guide mRNA
      cleavage, translational arrest, and heterochromatin formation in RNA interference
      (RNAi). To delineate the target region of RNAi, a construct harboring a
      transcriptional fusion between parts of the target mRNA and the beta
      glucuronidase gene was biolistically delivered into tobacco leaves showing an
      RNAi phenotype and the assay sequence was transiently expressed. The RNAi effect
      was monitored by amplification of this chimeric transcript. By using this assay
      method, we addressed the transitive RNA silencing of a tobacco endoplasmic
      reticulum omega-3 fatty acid desaturase gene (NtFAD3). In the NtFAD3 RNAi plants,
      the target region of RNAi was restricted in the inducer region corresponding to a
      stem sequence of the hairpin double-stranded RNA, indicating that endogenous
      NtFAD3 mRNA was not a template for an RNA-dependent RNA polymerase. The secondary
      NtFAD3 siRNAs were produced in the crossbred plants between the NtFAD3
      overexpressed plant and the NtFAD3 RNAi plant. Similarly, the secondary siRNAs
      were generated in the systemically silenced scion. Although these secondary
      siRNAs originated preferentially from the 3' region downstream of the inducer
      region, the secondary siRNAs produced in the silenced scion (non-cell autonomous
      secondary siRNAs) resulted in the strong degradation of the target mRNA, but the
      secondary siRNAs in the crossbred plants (cell-autonomous secondary siRNAs)
      showed limited RNA degradation activity. These results showed that this in vivo
      assay for determination of RNAi efficiency is a useful tool to delineate RNAi
      mechanisms.

PMID- 17225954
TI  - The sugar model: autocatalytic activity of the triose-ammonia reaction.
AB  - Reaction of triose sugars with ammonia under anaerobic conditions yielded
      autocatalytic products. The autocatalytic behavior of the products was examined
      by measuring the effect of the crude triose-ammonia reaction product on the
      kinetics of a second identical triose-ammonia reaction. The reaction product
      showed autocatalytic activity by increasing both the rate of disappearance of
      triose and the rate of formation of pyruvaldehyde, the product of triose
      dehydration. This synthetic process is considered a reasonable model of origin-of
      life chemistry because it uses plausible prebiotic substrates, and resembles
      modern biosynthesis by employing the energized carbon groups of sugars to drive
      the synthesis of autocatalytic molecules.

PMID- 17225955
TI  - An intimate interplay between precocious, migrating pericytes and endothelial
      cells governs human fetal brain angiogenesis.
AB  - In order to better understand the process of angiogenesis in the developing human
      brain, we have examined the spatial relationship and relative contributions of
      endothelial cells and pericytes, the two primary cell types involved in vessel
      growth, together with their relation with the vascular basement membrane.
      Pericytes were immunolocalized through use of the specific markers nerve/glial
      antigen 2 (NG2) proteoglycan, endosialin (CD248) and the platelet-derived growth
      factor receptor beta (PDGFR-beta), while endothelial cells were identified by the
      pan-endothelial marker CD31 and the blood brain barrier (BBB)-specific markers
      claudin-5 and glucose transporter isoform 1 (GLUT-1). The quantitative analysis
      demonstrates that microvessels of the fetal human telencephalon are characterized
      by a continuous layer of activated/angiogenic NG2 pericytes, which tightly invest
      endothelial cells and participate in the earliest stages of vessel growth.
      Immunolabelling with anti-active matrix metalloproteinase-2 (aMMP-2) and anti
      collagen type IV antibodies revealed that aMMP-2 producing endothelial cells and
      pericytes are both associated with the vascular basement membrane during vessel
      sprouting. Detailed localization of the two vascular cell types during
      angiogenesis suggests that growing microvessels of the human telencephalon are
      formed by a pericyte-driven angiogenic process in which the endothelial cells are
      preceded and guided by migrating pericytes during organization of the growing
      vessel wall.

PMID- 17225956
TI  - Lower HDL-cholesterol among healthy middle-aged Japanese-Brazilians in Sao Paulo
      compared to Natives and Japanese-Brazilians in Japan.
AB  - Blood lipid levels are determined by a combination of genetic and environmental
      factors. Higher than average values of high-density lipoprotein cholesterol (HDL
      cholesterol) have been observed in people of Japanese ethnicity. The aim of this
      study was to investigate whether Japanese immigrants to Brazil and subsequent
      generations maintain the protective benefits associated with higher levels of HDL
      cholesterol, and to examine the potential associations between HDL-cholesterol
      and a variety of other blood lipids, anthropometric and lifestyle factors.
      Healthy men and women aged 35 years and older who were Native Japanese (n = 198)
      or Japanese-Brazilians (JB) living in Sao Paulo, Brazil (n = 198) and in some
      Japanese cities (n = 246) were investigated. Anthropometric variables, blood
      lipids including HDL-cholesterol, and lifestyle factors were assessed. Serum HDL
      cholesterol was observed to be lower for JB in Sao Paulo (both women and men)
      compared with Natives and JB in Japan. Among the groups, triglycerides, waist
      circumference, LDL-cholesterol, meat intake, stress, and smoking were observed to
      be independently negatively associated with HDL-cholesterol, whereas total
      cholesterol, fish intake, and physical activity were positively associated. Lower
      levels of HDL-cholesterol among both men and women of JB in Sao Paulo compared
      with both other groups were confirmed even after lifestyle adjustments. Our
      findings highlight the significantly lower levels of HDL-cholesterol among
      Japanese-Brazilians living in Sao Paulo city compared to Japanese-Brazilians and
      Native Japanese residing in Japan. Although several lifestyle factors were found
      to be significantly associated with HDL-cholesterol, they cannot adequately
      explain the role of the Brazilian cultural environment on HDL-cholesterol levels.

PMID- 17225957
TI  - Early-life and adult socioeconomic status and inflammatory risk markers in
      adulthood.
AB  - BACKGROUND: Associations between childhood and adult socioeconomic status (SES)
      and adult levels of inflammatory markers (C-reactive protein [CRP], fibrinogen,
      white blood cell count [WBC], and von Willebrand factor [vWF]) were examined in
      the Atherosclerosis Risk in Communities (ARIC) Study cohort. METHODS: A total of
      12,681 white and African-American participants provided information on SES (via
      education and social class) and place of residence in childhood and adulthood.
      Residences were linked to census data for neighborhood SES information. Multiple
      imputation was used to impute missing data. Hierarchical and linear regression
      were used to estimate the effects of SES and possible mediation by adult
      cardiovascular disease (CVD) risk factors. FINDINGS: Low childhood social class
      and education were associated with elevated levels of CRP, fibrinogen, WBC, and
      vWF (increments of 17%, 2%, 4% and 3% for lowest versus highest education in
      childhood, respectively) among whites. Findings were less consistent among
      African-Americans. Adult SES was more strongly associated with inflammation than
      childhood SES. Individual-level SES measures were more consistently associated
      with inflammation than neighborhood-level measures. Fibrinogen and WBC showed the
      most consistent associations with SES; the largest changes in inflammation by SES
      were observed for CRP. Covariate adjustment strongly attenuated these
      associations. Mediation of the SES-inflammation associations by BMI, smoking and
      HDL cholesterol (HDL-C) are suggested by these data. CONCLUSION: Low individual-
      and neighborhood-level SES in childhood and adulthood are associated with modest
      increments in adult inflammatory burden. These associations may operate through
      the influence of low SES on traditional CVD risk factors, especially BMI, smoking
      and HDL-C.

PMID- 17225958
TI  - Patterns of bias due to differential misclassification by case-control status in
      a case-control study.
AB  - BACKGROUND: Case-control study is still one of the most commonly used study
      designs in epidemiological research. Misclassification of case-control status
      remains a significant issue because it will bias the results of a case-control
      study. There exist two types of misclassification, differential versus
      nondifferential. It is commonly accepted that nondifferential misclassification
      will bias the results of the study towards the null hypothesis. Conversely, no
      reports have assessed the impact and direction of differential misclassification
      on odds ratio (OR) estimate. The goal of the present study is to demonstrate by
      statistical derivation that patterns exist on the bias induced by differential
      misclassification. METHODS: Based on a 2 x 2 case-control study design, we derive
      the odds ratio without misclassification, and those with misclassification
      according to: (1) controls are misclassified as cases by exposure status; (2)
      cases are misclassified as controls by exposure status; and (3) both controls and
      cases are misclassified by exposure status simultaneously. Furthermore,
      mathematical derivations are shown for each of the ratios of the two odds ratios
      with and without misclassification. These methods are carried out by simulation
      analyses. RESULTS: Simulation analyses show that quite a number of biased odds
      ratios tend to move away from the null hypothesis and result in approaching zero
      or infinity with increasing proportion of misclassification among cases,
      controls, or both. These patterns are associated with the exposure status and the
      values of unbiased odds ratio (<1, 1, or >1). CONCLUSIONS: Our findings suggest
      that, unlike nondifferential misclassification, differential misclassification of
      case-control status in a case-control study may not weaken the exposure-outcome
      association towarding the null hypothesis. Care needs to be taken for
      interpreting the results of a case-control study when there exists differential
      misclassification bias, a practical issue in epidemiological research.

PMID- 17225959
TI  - From counterfactuals to sufficient component causes and vice versa.

PMID- 17225960
TI  - Short-term exposure to somatostatin or muscarinic agonists reduce acetylcholine
      induced 3H-MPP+ release from bovine adrenal medullary cells.
AB  - The aim of this work was to investigate the effect of a short-term exposure to
      somatostatin (SS), its receptors (SSTR) selective agonists as well as muscarinic
      receptors agonists upon acetylcholine-induced release of (3)H-MPP(+ )from bovine
      adrenal medullary cells. Acetylcholine (ACH, 100, 500 microM) was found to
      increase the release of (3)H-MPP(+ )by these cells (to 175 and 171% of basal
      release, respectively). ACH-elicited (3)H-MPP(+) release was significantly
      reduced by hexamethonium (100 microM) and atropine (100 microM), selective
      nicotinic and muscarinic antagonists, respectively. Previous exposure to any of
      two muscarinic agonists, oxotremorine or pilocarpine, led to a significant
      reduction of (3)H-MPP(+) release in response to 100 microM ACH, to about a
      maximum of 51% and 78% of control, respectively. Somatostatin (SS, 0.01-0.1
      microM), previously applied to the preparation, depressed ACH-elicited (3)H-MPP(+
      )release by 25-27%, but only when a 500 microM ACH concentration was used. The
      inhibition exerted by SS upon ACH-evoked (3)H-MPP(+) release appeared to be
      mediated by its SSTR: (1) SSTR2, 3 and 4 subtype agonists mimicked the effects
      seen with SS, and (2) the SSTR non-selective antagonist, cyclo-SS, counteracted
      the SS inhibitory effect. When SS was tested in the presence of any of the
      muscarinic agonists, oxotremorine or pilocarpine, its inhibitory effect on 500
      microM ACH-induced (3)H-MPP(+) release was no longer detectable. These results,
      showing a somewhat similar effect of short-term exposure to SS and muscarinic
      agonists over ACH-induced release of (3)H-MPP(+), as well as the loss of effect
      of SS by the presence of the muscarinic agonists, suggest that these compounds
      may share signalling pathways.

PMID- 17225961
TI  - Cannibalism and intraguild predation in Typhlodromus exhilaratus and T. phialatus
      (Acari: Phytoseiidae) under laboratory conditions.
AB  - Two species of Phytoseiidae are found in the same agroecosystem: Typhlodromus
      exhilaratus prevails in vine plots, while T. phialatus prevails in uncultivated
      surrounding areas. The objective of the present paper was to investigate whether
      the poor settlement of T. phialatus in vine plots can be explained by intraguild
      predation of these two species and/or cannibalism. Predatory abilities of the
      females on larvae and protonymphs were studied under laboratory conditions. A
      first experiment was conducted with only conspecific or heterospecific phytoseiid
      prey, in a second experiment Tetranychus urticae eggs were added to the
      phytoseiid prey. Oviposition, prey consumption, and escape rates of females were
      recorded. Oviposition and intraguild predation rates were higher for T.
      exhilaratus than for T. phialatus. Typhlodromus exhilaratus consumed fewer
      conspecifics than heterospecific phytoseiids, and oviposited when feeding on both
      diets. Typhlodromus phialatus consumed equal amounts of con- and heterospecifics.
      Although these two generalist predators belong to the type III defined by
      McMurtry and Croft (Annual Review of Entomology 42:291-321, 1997), our results
      suggest that they have different predation behaviour. However, because these
      results were obtained in experiments where no choice was given between the two
      phytoseiid species, they are difficult to link to previous studies conducted on
      the intraguild predation of the Phytoseiidae. The greater voracity and
      prolificacy of T. exhilaratus could partially explain the poor settlement of T.
      phialatus in vineyards and the predominance of T. exhilaratus. However, a full
      understanding of this phenomenon will require the study of other factors, such as
      susceptibility to pesticides and micro-climatic conditions, as well as the
      ability to cope with different food sources and host plants.

PMID- 17225962
TI  - The natural vegetation responses to the groundwater change resulting from
      ecological water conveyances to the lower Tarim River.
AB  - This paper takes the ecological water conveyance project (EWCP) that transfers
      water from the Bosten Lake, to Daxihaizi Reservoir, and finally to the Taitema
      Lake as a case study to analyze the dynamic change of the groundwater depth, the
      vegetation responses to the elevation of the groundwater depth as well as the
      relationship between the groundwater depth and the natural vegetation. The
      results from many years' monitoring in field indicate: (1) the groundwater depth
      has been elevating gradually with the increase in the times of watering and the
      elevation range has been expanding continuously in the lower reaches of Tarim
      River. Correspondingly, the natural vegetation has a favorable response to the
      elevation of the groundwater depth. The change of the natural vegetation has
      accordance with that of the groundwater depth. Such facts not only show that
      groundwater is a key factor to the growth of the native vegetation but also prove
      it is feasible that the degraded ecosystem can be restored and protected by the
      EWCP; (2) the results of analysis of the spatial-temporal response of the natural
      vegetation to watering reveals that the beneficial influence of the EWCP on the
      ecosystem in the lower Tarim River is a long-term process; (3) in terms of the
      function and structure of ecosystem after watering in the lower reaches of Tarim
      River, the EWCP does not still reach the goal of ecological restoration at a
      large spatial scale at present. Based on such monitoring results, some
      countermeasures and suggestions for the future restoration strategy are proposed
      so as to provide a theoretical basis for restoring and protecting the ecosystem
      in Tarim River, and meanwhile it can also provide some scientific references for
      implementing the similar ecological projects in other areas.

PMID- 17225963
TI  - Effects of validamycin on some enzymatic activities in soil.
AB  - There have been few investigations of the possible effects of validamycin on the
      enzymatic activities in soil. The objective of this present work was to study the
      short-term influence of enzymatic activity in validamycin treated soils. The
      results showed that high dose of validamycin introduced into soil had an
      significant effect on soil enzymatic activities, the degree of inhibition or
      promotion of enzymatic activities was not only related to the concentration of
      validamycin, but also to the remain time. Compared with the control (non
      treatment with validamycin), 240 ml.mg(-1) validamycin treatment caused a
      significant decrease (14%) of soil catalase activity; validamycin also inhibited
      urease activity to 67.3%, but subsequently, validamycin stimulated its activity
      higher than that of the control. Only the highest dose stimulated acid phophatase
      activities by 29.7%, and other concentration treatments had no effects on these
      enzymatic activities. The above results indicated that validamycin had effects on
      soil enzyme, but the effective time was short. It is also interesting to
      speculate that validamycin can be easily used by the soil microorganism as carbon
      source and energy.

PMID- 17225965
TI  - Ascertainment bias and the pattern of nucleotide diversity at the human ALDH2
      locus in a Japanese population.
AB  - Many East Asian human populations harbor a high-frequency deficiency allele for
      the aldehyde dehydrogenase 2 (ALDH2) enzyme, a critical protein involved in the
      metabolism of ethanol. Here we use resequencing and long-range SNP haplotype data
      from a Japanese sample to test whether patterns of nucleotide diversity and
      linkage disequilibrium at this locus are compatible with a standard neutral model
      of evolution. Examination of the pattern of polymorphism at a locus such as this,
      where the frequency of a common allele is known a priori, introduces an
      ascertainment bias that must be corrected for in analyses of the frequency
      spectrum of polymorphisms. We apply a flexible and generally applicable
      simulation approach to correct for this bias in our ALDH2 data and, also, to
      explore the effect of bias on the commonly used summary statistics Tajima's D, Fu
      and Li's D, and Fay and Wu's H. Our study finds no evidence that the pattern of
      genetic variation at ALDH2 differs from that expected under a standard neutral
      model. However, our general examination of ascertainment bias indicates that a
      priori knowledge of segregating alleles greatly affects the expected
      distributions of summary statistics. Under many parameter combinations we find
      that ascertainment bias introduces an elevated rate of false positives when
      summary statistics are used to test for deviations from a standard neutral model.
      However, we also show that over a wide range of conditions the power of all
      summary statistics can be greatly increased by incorporating prior knowledge of
      segregating alleles.

PMID- 17225966
TI  - Molecular phylogeny, evolution, and functional divergence of the LSD1-like gene
      family: inference from the rice genome.
AB  - The identification of LSD1-like genes in parasite, green algae, moss, pine, and
      monocot and dicot species allowed us to trace the phylogenetic history of this
      gene family. Computational analysis showed that the diversification of members of
      this family could be dated back to the early stage of plant evolution. The
      evolution of plant LSD1-like genes was possibly shaped by two duplication events.
      These proteins, which contain three copies of the LSD1 zinc finger (zf-LSD1)
      domain within their entire polypeptides and play crucial roles in modulating
      disease defense and cell death, resulted from the second duplication. A gain of
      zf-LSD1 domain model was reasonable for explaining the origination of three-zf
      LSD1 domain-containing proteins. The zf-LSD1 domain phylogeny showed that the
      middle (M) and C-terminal (C) domains originated from a common ancestor; the N
      terminal (N) domain might be more ancient than the former two. The divergence of
      the N, M, and C domains was well before the monocot-dicot split. Coevolution
      analysis revealed that four intramolecular domain pairs, including the N domain
      and the interregion between the M and the C domains (INTER2), the M and C domain,
      the N- and C-terminus, and the M domain and C-terminus, possibly coevolved during
      the evolution of three-zf-LSD1 domain-containing proteins. The three zf-LSD1
      domains are evolutionary conserved. Thus, the differences at the N- and C
      terminus would be crucial for functional specificity of LSD1 genes. Strong
      functional constraints should work on the zf-LSD1 domains, whereas reduced
      functional constraint was found in the INTER2 region. Functional divergence
      analysis showed that three-zf-LSD1 domain-containing proteins were significantly
      functionally divergent from those proteins containing only one zf-LSD1 domain, a
      result demonstrating that shifted evolutionary rates between the two clusters
      were significantly different from each other.

PMID- 17225968
TI  - Extensive iatrogenic aortic dissection during renal angioplasty: successful
      treatment with a covered stent-graft.
AB  - An extensive iatrogenic aortic type B dissection during percutaneous transluminal
      renal angioplasty (PTRA) for bilateral renal artery stenosis was treated with a
      covered stent placed in the right renal artery. Control angiography confirmed
      closure of the entry. Postprocedural CT demonstrated a thick intramural hematoma
      (IMH) up to the left subclavian artery. CT follow-up at 8 months showed an almost
      complete resorption of the IMH. While medical treatment is the standard therapy
      for type B dissections, closure of the intimal tear with a covered stent may be
      an additional option in extensive cases during PTRA.

PMID- 17225967
TI  - Unusual origin of a nuclear pseudogene in the Italian wall lizard: intergenomic
      and interspecific transfer of a large section of the mitochondrial genome in the
      genus Podarcis (Lacertidae).
AB  - Two distinct cytochrome b-like sequences were discovered in the genome of
      Podarcis sicula. One of them represents a nuclear copy of a mitochondrial
      sequence (numt-sic) differing by 14.3% from the authentic mitochondrial (mt)
      sequence obtained from the same individual. This numt, however, differs by only
      2.7% from the mt sequence found in one population of Podarcis muralis, a related
      species in which no corresponding numt was detected. The numt-sic sequence
      extends over at least 7637 bp and is homologous to a section of the mt genome
      spanning from the tRNA-Lys to the tRNA-Pro gene. Premature mt stop codons were
      detected in two of the nine protein coding genes of numt-sic. The distribution of
      substitutions among the three codon positions and the transition/transversion
      ratio of the numt-sic sequence resemble, with few exceptions, those of functional
      mt genes, indicating a rather recent transfer to the nucleus. Phylogenetic
      analyses performed on the data set including P. sicula numt-cytb sequences as
      well as mt-cytb sequences from the same individuals and mt sequences of various
      P. muralis populations suggest that numt-sic originated in P. muralis. In a
      geographic survey, P. sicula populations belonging to different mt lineages,
      covering most of the distribution area, were screened for the presence of numt
      sic and for a 15-bp duplication polymorphism in the numt-nd5 sequence. Our
      results suggest that numt-sic has spread rapidly through the species range via
      sexual transmission, thereby being transferred to populations belonging to well
      separated mt lineages that diverged 1-3 Mya.

PMID- 17225969
TI  - Magnetic resonance angiography of uterine artery: changes with embolization using
      gelatin sponge particles alone for fibroids.
AB  - PURPOSE: To assess uterine artery recanalization, together with tumor
      devascularization, after embolization using gelatin sponge particles alone for
      fibroids. METHODS: Twenty-seven patients underwent uterine artery embolization
      (UAE) for fibroids using only gelatin sponge particles. The angiographic endpoint
      of embolization was defined as near stasis of contrast medium in the ascending
      segment of the uterine artery. All patients underwent contrast-enhanced magnetic
      resonance angiography (MRA) before and 4 months after UAE, and contrast-enhanced
      magnetic resonance imaging (CE-MRI) before, 1 week after, and 4 months after UAE.
      The visualization of the uterine arteries before and 4 months after UAE was
      assessed using MRA. The infarction rates of the largest tumor were assessed using
      CE-MRI 1 week after UAE. RESULTS: MRA 4 months after UAE showed 100% (53/53) of
      the descending and transverse segments, and 88% (43/49) of the ascending segments
      that had been noted on baseline MRA. The visualization of the ascending segments
      on MRA 4 months after UAE was identical to that on baseline MRA in 20 of 27
      patients (74%). CE-MRI showed complete infarction of the largest tumor in 22 of
      27 patients (81%), and 90-99% infarction of the largest tumor in the remaining 5
      of 27 patients (19%). CONCLUSION: Based on the MR study, in most cases uterine
      artery recanalization occurred, together with sufficient devascularization of
      fibroids, after UAE using gelatin sponge particles alone.

PMID- 17225970
TI  - Transcatheter embolization of a renal arteriovenous fistula complicated by an
      aneurysm of the feeding renal artery.
AB  - Renal arteriovenous fistula (AVF) is rare. Renal AVF complicated by aneurysm of
      the feeding artery presents a technical challenge for endovascular treatment. We
      report a case managed by covered stenting of the renal artery aneurysm, coil
      embolization of the fistula, and bare stenting of the aorta.

PMID- 17225971
TI  - Porcine transfer study: virtual reality simulator training compared with porcine
      training in endovascular novices.
AB  - PURPOSE: To compare the learning of endovascular interventional skills by
      training on pig models versus virtual reality simulators. METHODS: Twelve
      endovascular novices participated in a study consisting of a pig laboratory (P
      Lab) and a virtual reality laboratory (VR-Lab). Subjects were stratified by
      experience and randomized into four training groups. Following 1 hr of didactic
      instruction, all attempted an iliac artery stenosis (IAS) revascularization in
      both laboratories. Onsite proctors evaluated performances using task-specific
      checklists and global rating scales, yielding a Total Score. Participants
      completed two training sessions of 3 hr each, using their group's assigned method
      (P-Lab x 2, P-Lab + VR-Lab, VR-Lab + P-Lab, or VR-Lab x 2) and were re-evaluated
      in both laboratories. A panel of two highly experienced interventional
      radiologists performed assessments from video recordings. ANCOVA analysis of
      Total Score against years of surgical, interventional radiology (IR) experience
      and cumulative number of P-Lab or VR-Lab sessions was conducted. Inter-rater
      reliability (IRR) was determined by comparing proctored scores with the video
      assessors in only the VR-Lab. RESULTS: VR-Lab sessions improved the VR-Lab Total
      Score (beta = 3.029, p = 0.0015) and P-Lab Total Score (beta = 1.814, p =
      0.0452). P-Lab sessions increased the P-Lab Total Score (beta = 4.074, p <
      0.0001) but had no effect on the VR-Lab Total Score. In the general statistical
      model, both P-Lab sessions (beta = 2.552, p = 0.0010) and VR-Lab sessions (beta =
      2.435, p = 0.0032) significantly improved Total Score. Neither previous surgical
      experience nor IR experience predicted Total Score. VR-Lab scores were
      consistently higher than the P-Lab scores (Delta = 6.659, p < 0.0001). VR-Lab IRR
      was substantial (r = 0.649, p < 0.0008). CONCLUSIONS: Endovascular skills learned
      in the virtual environment may be transferable to the real catheterization
      laboratory as modeled in the P-Lab.

PMID- 17225973
TI  - Colorectal stenting: an effective therapy for preoperative and palliative
      treatment.
AB  - PURPOSE: To demonstrate the effectiveness of preoperative and palliative
      colorectal stent placement in acute colonic obstruction. METHODS: Sixty-seven
      consecutive patients (mean age 67.3 years, range 25-93 years) with clinical and
      radiological signs of colonic obstruction were treated: 45 (67%) preoperatively
      and 22 (33%) with a palliative intent. In 59 patients (88%) the obstruction was
      malignant, while in 8 (12%) it was benign. A total of 73 enteric Wallstents were
      implanted under combined fluoroscopic/endoscopic guidance. RESULTS: Forty-five
      patients were treated preoperatively with a technical success rate of 84%, a
      clinical success rate of 83%, and a complication rate of 16%. Of the 38 patients
      who were successfully stented preoperatively, 36 (95%) underwent surgery 2-22
      days (mean 7.2 days) after stent insertion. The improved general condition and
      adequate bowel cleansing allowed single-stage tumor resection and primary end-to
      end anastomosis without complications in 31 cases (86% of all operations), while
      only 5 patients had colostomies. Stent placement was used as the final palliative
      treatment in 22 patients. The technical success rate was 95%, the clinical
      success rate 72%, and the complication rate relatively high at 67%, caused by
      reocclusion in most cases. After noninvasive secondary interventions (e.g., tube
      placement, second stenting, balloon dilatation) the secondary patency of stents
      was 71% and mean reported survival time after stent insertion was 92 days (range
      10-285 days). CONCLUSION: Preoperative stent placement in acute colonic
      obstruction is minimally invasive and allows an elective one-stage surgery in
      most cases. Stent placement also proved a valuable alternative to avoid colostomy
      in palliation.

PMID- 17225972
TI  - Evaluation of intrahepatic perfusion on fusion imaging using a combined CT/SPECT
      system: influence of anatomic variations on hemodynamic modification before
      installation of implantable port systems for hepatic arterial infusion
      chemotherapy.
AB  - BACKGROUND: In some patients with hepatic tumors, anatomic variations in the
      hepatic arteries may require hemodynamic modification to render effective hepatic
      arterial infusion chemotherapy delivered via implantable port systems. We used a
      combined CT/SPECT system to obtain fused images of the intrahepatic perfusion
      patterns in patients with such anatomic variations and assessed their effects on
      the treatment response of hepatic tumors. METHODS: Using a combined SPECT/CT
      system, we obtained fused images in 110 patients with malignant liver tumors (n =
      75) or liver metastasis from unresectable pancreatic cancer (n = 35). Patients
      with anatomic hepatic arteries variations underwent hemodynamic modification
      before the placement of implantable port systems for hepatic arterial infusion
      chemotherapy. We evaluated their intrahepatic perfusion patterns and the initial
      treatment response of their liver tumors. The perfusion patterns on the fused
      images were classified as homogeneous, local hypoperfusion, and/or perfusion
      defect. Using the WHO criteria of complete response (CR), partial response (PR),
      no change (NC), and progressive disease (PD), we evaluated the patients' tumor
      responses after 3 months on multislice helical CT scans. The treatment was
      regarded as effective in patients who achieved a complete response or partial
      response. RESULTS: Anatomic hepatic artery variations were present in 15 of the
      110 patients (13.6%); 5 manifested replacement of the left hepatic artery (LHA),
      8 of the right hepatic artery (RHA), and 1 each had replacement of the RHA and
      LHA, and replacement of the LHA plus an accessory RHA. In 13 of these 15 patients
      (87%), occlusion with metallic coils was successful. On fusion imaging, the
      perfusion patterns were recorded as homogeneous in 6 patients (43%), as
      hypoperfusion in 7 (50%), and 1 patient had a perfusion defect (7.1%) in the
      embolized arterial region. Of the 8 patients with RHA replacement, 4 manifested a
      homogeneous distribution and 3 hypoperfusion. In 2 of 5 patients with LHA
      replacement, the distribution was homogeneous. In 1 patient with RHA and LHA
      replacement, and in 1 patient with LHA replacement and an accessory RHA, we noted
      hypoperfusion in the RHA territory. All 6 patients with homogeneous distribution
      were classified as PR or NC on follow-up multidetector CT. Of the 7 patients
      manifesting hypoperfusion, 3 were classified as PD (43%), 3 as NC (43%), and 1 as
      PR (14%) on follow-up CT. CONCLUSION: Hemodynamic modification of anatomic
      hepatic artery variations resulted in hypoperfusion on fusion images. Differences
      in the intrahepatic perfusion patterns may affect the response to hepatic
      arterial infusion chemotherapy.

PMID- 17225974
TI  - Hereditary multiple exostoses with pseudoaneurysm.
AB  - A 16-year-old male patient with hereditary multiple exostoses (HME) was found to
      have a pseudoaneurysm of the left popliteal artery caused by osteochondroma in
      the lower femur. The diagnosis was confirmed by ultrasound, magnetic resonance
      imaging and magnetic resonance angiography without the need to perform an
      angiogram. The osteochondroma was excised and the popliteal artery was repaired
      with a saphenous graft. Vascular complications are extremely rare in HME,
      pseudoaneurysm being the most common and mostly located in the popliteal artery.
      This complication should be considered in young HME patients with a mass at the
      knee region. The radiological spectrum of investigations allows the diagnosis of
      this complication with proper and less invasive management procedures for the
      patient.

PMID- 17225975
TI  - Evaluation of extrahepatic perfusion of anticancer drugs in the right gastric
      arterial region on fused images using combined CT/SPECT: is extrahepatic
      perfusion predictive of gastric toxicity?
AB  - BACKGROUND: Hepatic arterial infusion (HAI) chemotherapy is effective for
      treating primary and metastatic carcinomas of the liver. Since hepatic arteries
      also supply the stomach and duodenum, HAI may result in unwanted infusion into
      the upper gastrointestinal tract and consequent gastric toxicity. Using fused
      images obtained with a combined SPECT/CT system, we assessed extrahepatic
      perfusion (EHP) and its correlation with gastrointestinal toxicity in patients
      receiving HAI. METHODS: We studied 41 patients with primary or metastatic
      carcinoma of the liver who received HAI chemotherapy consisting of 5-fluorouracil
      and cisplatin. All underwent abdominal SPECT using a (99m)Tc-MAA (185 MBq)
      instrument and an injection rate of 0.1 ml/min, identical to the chemotherapy
      infusion rate. Delivery was through an implantable port. We analyzed the
      distribution of the anticancer agent on fused images and the relationship between
      EHP of the right gastric arterial region and gastric toxicity. All patients
      underwent esophagogastroduodenoscopy (EGDS). RESULTS: Of the 41 patients, 11
      (27%) manifested enhancement of the duodenal and gastric pyloric region on fused
      images. EGDS at the time of reservoir placement detected gastric ulcers in 10 of
      these patients. CONCLUSION: Fusion imaging with combined SPECT/CT reflects the
      actual distribution of the infused anticancer agents. The detection of EHP on
      fused images is predictive of the direct gastric toxicity from anticancer agents
      in patients undergoing HAI.

PMID- 17225976
TI  - Using evoked potentials to match interaural electrode pairs with bilateral
      cochlear implants.
AB  - Bilateral cochlear implantation seeks to restore the advantages of binaural
      hearing to the profoundly deaf by providing binaural cues normally important for
      accurate sound localization and speech reception in noise. Psychophysical
      observations suggest that a key issue for the implementation of a successful
      binaural prosthesis is the ability to match the cochlear positions of stimulation
      channels in each ear. We used a cat model of bilateral cochlear implants with
      eight-electrode arrays implanted in each cochlea to develop and test a
      noninvasive method based on evoked potentials for matching interaural electrodes.
      The arrays allowed the cochlear location of stimulation to be independently
      varied in each ear. The binaural interaction component (BIC) of the electrically
      evoked auditory brainstem response (EABR) was used as an assay of binaural
      processing. BIC amplitude peaked for interaural electrode pairs at the same
      relative cochlear position and dropped with increasing cochlear separation in
      either direction. To test the hypothesis that BIC amplitude peaks when electrodes
      from the two sides activate maximally overlapping neural populations, we measured
      multiunit neural activity along the tonotopic gradient of the inferior colliculus
      (IC) with 16-channel recording probes and determined the spatial pattern of IC
      activation for each stimulating electrode. We found that the interaural electrode
      pairings that produced the best aligned IC activation patterns were also those
      that yielded maximum BIC amplitude. These results suggest that EABR measurements
      may provide a method for assigning frequency-channel mappings in bilateral
      implant recipients, such as pediatric patients, for which psychophysical measures
      of pitch ranking or binaural fusion are unavailable.

PMID- 17225977
TI  - Non-radical diagnostic biopsies do not negatively influence melanoma patient
      survival.
AB  - BACKGROUND: In fair-skinned Caucasian populations both the incidence and
      mortality rates of cutaneous melanoma have been increasing over the past decades.
      With adjuvant therapies still being under investigation, early detection is the
      only way to improve melanoma patient survival. The influence of incisional
      biopsies on melanoma patient survival has been discussed for many years. This
      study investigates both the influence of diagnostic biopsy type and the presence
      of residual tumor cells in the re-excision specimen on disease free and overall
      survival. METHODS: After (partial) removal of a pigmented skin lesion 471
      patients were diagnosed with stage I/II melanoma and underwent re-excision and a
      sentinel node biopsy. All patients were followed prospectively, mean follow up >5
      years. Patients were divided according to their diagnostic biopsy type (wide
      excision biopsy, narrow excision biopsy, excision biopsy with positive margins
      and incisional biopsy) and the presence of residual tumor cells in their re
      excision specimen. Survival analysis was done using Cox's proportional hazard
      model adjusted for eight important confounders of melanoma patient survival.
      RESULTS: The diagnostic biopsy was wide in 279 patients, narrow in 109 patients,
      52 patients underwent an excision biopsy with positive margins and 31 patients an
      incisional biopsy. In 41 patients residual tumor cells were present in the re
      excision specimen. Both the diagnostic biopsy type and the presence of tumor
      cells in the re-excision specimen did not influence disease free and overall
      survival of melanoma patients. CONCLUSIONS: Non-radical diagnostic biopsies do
      not negatively influence melanoma patient survival.

PMID- 17225978
TI  - Comment to "Effect of primary tumor extirpation in breast cancer patients who
      present with stage IV disease and intact primary tumor" by G V Babiera, R Rao, L
      Feng, F Meric-Bernstam, H M Kuerer, S E Singletary, K K Hunt, M I Ross, K M Gwyn,
      B W Feig, F C Ames, G N Horthobagyi. Ann Surg Oncol 2006;13:776-782.

PMID- 17225979
TI  - Combined radioguided nonpalpable lesion localization and sentinel lymph node
      biopsy for early breast carcinoma.
AB  - BACKGROUND: The aim of this study was to test a new strategy for radioguided
      management of malignant or suspicious nonpalpable breast lesions, with a
      combination of radioguided occult lesion localization (ROLL), sentinel lymph node
      (SLN) mapping, and, if necessary, immediate local surgery and SLN biopsy with a
      single injection of (99m)Tc-labeled dextran for the whole procedure. METHODS: A
      total of 115 nonpalpable lesions were studied: 101 with high suspicion of
      malignancy from which frozen sections had been produced, and 14 carcinomas
      diagnosed by mammotomy. On the day before surgery, 0.2 mL of solution of dextran
      labeled with 15 MBq of (99m)Tc was injected into the center of the lesions under
      imaging guidance. All patients underwent lymphoscintigraphy and open-surgery
      biopsy guided by gamma probe, followed by radiographic verification of the
      specimen. If malignancy was detected, in cases of infiltrating or ductal
      carcinoma-in-situ with comedonecrosis or high nuclear grade, breast-conserving
      surgery and SLN biopsy were performed during the same operation. RESULTS: The
      combination of ROLL and SLN biopsy was feasible and practical. The rate of
      simultaneous SLN mapping by lymphoscintigraphy was 97.4% (112 of 115), and the
      confirmation rate for breast lesion removal by specimen radiography was 100%. It
      was known that 57 cases were malignant at the time of surgery. After segmental
      breast resection, SLN immediately underwent biopsy in 50 cases (34 infiltrating
      carcinomas and 16 ductal carcinoma-in-situ) with probe monitoring. Three were
      cytologically positive for metastasis and required full axillary dissection.
      CONCLUSIONS: ROLL and SLN biopsy are emerging procedures that can be used
      simultaneously. They permit exact breast lesion excision, immediate local breast
      surgery, and intraoperative SLN biopsy in a single procedure. The combination of
      radioguided nonpalpable lesion localization and SLN biopsy is a suitable
      alternative to working up subclinical imaging-detected breast carcinomas.

PMID- 17225980
TI  - Trends in the treatment and outcome of pancreatic cancer in the United States.
AB  - BACKGROUND: Although pancreatic cancer is the fourth leading cause of cancer
      death, few studies have evaluated population-based trends in diagnosis,
      management, and outcome. METHODS: We used the Surveillance, Epidemiology, and End
      Results (SEER) registry to evaluate treatment trends and outcomes for patients 18
      or older with pancreatic adenocarcinoma diagnosed from 1988 through 2002.
      RESULTS: We identified 38,073 patients diagnosed with pancreatic cancer over this
      15-year period; the age-adjusted incidence did not change over this period. Most
      patients were diagnosed with metastatic disease (50.3%), few of whom underwent
      irradiation or cancer-directed surgery (CDS). For patients with localized or
      regional disease (32.9%), 53% underwent some form of treatment. Importantly, the
      rate of CDS increased from 19% in 1988 to 35% in 2002 (P < 0.0001). In
      multivariate analysis, young age, married status, and localized disease were
      associated with significantly higher CDS rates. For patients with nonmetastatic
      disease, 2-year survival rate increased from 8% in 1988 to 15% in 2000. For
      patients with non-metastatic cancer who survived at least 3 months, CDS was
      associated with a significantly higher 2-year survival rate (CDS, 36%; non-CDS,
      10%). CONCLUSIONS: Most patients with pancreatic cancer, even at the end of our
      15-year study period, still presented with metastatic disease, and the survival
      rate for such patients did not change in a meaningful way over time. The
      proportion of patients with nonmetastatic pancreatic cancer who underwent
      potentially curative surgery increased over time in the U.S.; the 2-year survival
      rate for such patients improved, but remained poor.

PMID- 17225981
TI  - Low-dose interleukin-2 administered pre-operatively to patients with gastric
      cancer activates peripheral and peritumoral lymphocytes but does not affect
      prognosis.
AB  - BACKGROUND: There is evidence that cancer is immunogenic under certain
      situations. IL-2 is described to stimulate an effective antitumor immune response
      in vitro and in vivo. The ability of cancer patients to undergo surgical
      resection is still the most important prognostic factor for many solid tumors,
      including gastric adenocarcinoma. The host immune system may be further
      compromised by surgical procedures leading to a generalized state of
      immunodepression in the post-operative period. The aim of this randomized case
      control study is to evaluate the effects of pre-operative low-dose IL-2 treatment
      on patients with gastric adenocarcinoma who undergo surgery. METHODS: Sixty-eight
      patients with gastric adenocarcinoma were enrolled in the study and randomized in
      two groups: 36 patients were pre-treated with IL-2 and 32 underwent surgery
      without any treatment. Total peripheral WBC, neutrophils, CD3(+) T, CD4(+) T,
      CD8(+) T and NK cells were obtained before and after surgery, at different times.
      Peritumoral infiltration was analyzed on all surgical specimens. Overall survival
      and relapse-free survival were studied with a median follow-up of 51 months.
      RESULTS: Low-dose IL-2 treatment resulted in an increase peritumoral lymphocytic
      and eosinophilic infiltrations and in a minor decrease in CD3(+) T and CD4(+) T
      cells after surgery (P < 0.05). A stepwise multivariate analysis revealed that
      overall survival and relapse-free survival were affected only by stage of tumor
      and age of patients. CONCLUSIONS: According to our data low-doses of IL-2
      administered pre-operatively to patients with gastric cancer activate peripheral
      and peri-tumoral lymphocytes but did not affect prognosis.

PMID- 17225982
TI  - Abdominal shape of gastric cancer patients influences short-term surgical
      outcomes.
AB  - BACKGROUND: There is a prevailing belief that both obesity and abdominal shape
      influence abdominal accessibility, and thus affect short-term surgical outcomes
      of gastric cancer surgery. METHODS: We measured the thickness of subcutaneous fat
      (SCF), abdominal anterior-posterior diameter (APD), transverse diameter (TD), and
      intra-abdominal fat volume (IFV) at the umbilicus level by using the abdominal CT
      scans of 291 gastric cancer patients who had undergone subtotal gastrectomy and
      D2 lymph node dissection. Clinicopathological factors including body mass index
      (BMI), APD, TD, IFV, and SCF and surgical outcomes, i.e., dissected lymph node
      number, morbidity, and mortality were analyzed. RESULTS: SCF thickness, APD, TD,
      IFV, and BMI mean values were 20.0 mm (range 2.0-64.0), 188.4 mm (range 128.0
      332.0), 301.4 mm (range 160.0-651.0), 198.3 mm(2) (range 123.4-312.1), and 23.9
      kg/m(2) (range 16.6-34.6), respectively. In male patients, APD was found to
      correlate with the number of retrieved lymph nodes (P = 0.045). Whereas in female
      patients, this was not the case (P = 0.093). Twenty-one patients experienced
      postoperative complications but no postoperative mortality occurred. Female
      patients who experienced postoperative complications had higher APD (32.9 +/-
      10.0 mm versus 26.1 +/- 7.9 mm, P = 0.044) and BMI (27.3 +/- 4.1 kg/m(2) versus
      24.3 +/- 3.5 kg/m(2), P = 0.049) values than those who did not. CONCLUSIONS: We
      conclude that obesity and abdominal shape of gastric cancer patients both
      influence the short-term surgical outcomes of subtotal gastrectomy with D2 lymph
      node dissection.

PMID- 17225985
TI  - [Risk communication through genetic counselling: requirements and problems].
AB  - Genetic counselling is the single most important instrument for the individual
      communication of genetic risks. Beyond medical and psychosocial purposes in terms
      of preparing diagnostic measures and coping with results, genetic counselling
      also serves as a means to ensure the clients' decision autonomy through
      adequately informed consent. Accordingly, indispensable preconditions of the
      counselling process are voluntariness, individuality, non-directiveness, and
      respect of the right not to know. However, the requirement that any genetic
      diagnosis should be embedded into genet ic counselling is all too often neglected
      in today's reality of medicine. Consequently, there is urgent need of legislation
      ensuring mandatory counselling at least before prenatal and predictive genetic
      testing. Additionally, clear standards must be established and enforced for the
      quality of the counselling process as well as for the qualification of
      counsellors, and sufficient personal and institutional resources must be
      provided.

PMID- 17225984
TI  - [Varicella during pregnancy and in neonates].
AB  - Varicella belongs to the most common vaccine-preventable diseases in Germany.
      During pregnancy, varicella may have serious consequences for the pregnant women
      and for the fetus or newborn. Pregnant women who contract varicella are at risk
      of pneumonia which must be regarded as a medical emergency. Chicken pox between
      the 5th and 24th weeks of pregnancy may lead to the congenital varicella
      syndrome. In case of maternal varicella during the last few weeks of pregnancy or
      shortly after delivery, the virus can cause chicken pox in the newborn. Life
      threaten ing disseminated neonatal varicella must be expected if the mother
      develops chicken pox between 5 days before and 2 days after delivery. Using
      currently available diagnostics, immuno-prophylactic and therapeutic
      opportunities, these serious consequences of varicella during pregnancy can be
      prevented.

PMID- 17225983
TI  - Standardized uptake value atlas: characterization of physiological 2-deoxy-2
      [18F]fluoro-D-glucose uptake in normal tissues.
AB  - PURPOSE: The purpose of this study was to map the distribution of 2-deoxy-2
      [18F]fluoro-D-glucose (FDG) uptake in organs of patients with no known
      abnormalities in those tissues. PROCEDURES: We measured maximum and mean
      standardized uptake values (SUV) from FDG-positron emission tomography
      (PET)/computed tomography (CT) obtained from 98 patients (48 males and 50
      females). RESULTS: Significant uptake (mean SUVmean>2.5) was visualized in the
      cerebellum (8.0+/-2.2), soft palate (2.92+/-0.86), palatine tonsils (3.45+/-1.4),
      lingual tonsils (3.08+/-1.05), sublingual glands (3.3+/-1.5), and testes (2.57+/
      0.56). Negative correlation for FDG uptake versus age was observed for the
      palatine tonsils, sublingual glands, and lungs (P<0.001). CONCLUSION: Better
      understanding of physiological uptake throughout the body is valuable for
      improved interpretive accuracy and should be useful for future semi-automated
      comparisons to a normal SUV database.

PMID- 17225986
TI  - [The National Genome Research Network. Genome research in Germany].
AB  - In 2001 Germany's Federal Ministry of Education and Research (BMFM) initiated the
      National Genome Research Network (NGFN). The goals of the NGFN are the
      investigation of the molecular basis of common diseases to improve new methods
      for prevention, diagnosis and therapy. The disease-oriented genome networks
      investigate cardiovascular diseases, cancer, diseases of the nervous system,
      diseases due to environmental factors and infection, and inflammation. They are
      supported by technological platforms and a component for technology transfer. The
      explicit aims include better integration of public health research and economy in
      order to gain an efficient economical and technological utilisation and
      application in community health. This article describes the creation of the NGFN
      in the context of international and national genome research, shows the structure
      and content of the NGFN and gives examples for NGFN research in networks on a
      highly, internationally recognised level.

PMID- 17225987
TI  - [Preimplantation genetic diagnosis. Ethical, social and legal aspects].
AB  - Preimplantation genetic diagnosis (PGD) undertakes an examination of an embryo
      outside the mother's womb subsequent to artificial insemination in order to
      identify a potential genetic and chromosomal impairment of that embryo. PGD is
      not being practiced in the Federal Republic of Germany since it cannot be
      reconciled with the provisions of the Embryo Protection Law. Objections have been
      raised against PGD based on ethical, religious and feminist arguments as well as
      on the grounds of legal framework policy. The essence of those objections relates
      to the fact that this method relativises the inviolability of the embryo in its
      early stages. Even human dignity itself is considered in danger. However, those
      objections have themselves caused demur. A variety of ethical reasons make it
      appear conceivable to allow PGD under narrowly defined conditions in medically
      founded cases. PGD can be used to the benefit of the health of both the pregnant
      mother and the expected children. In case PGD should be permitted, it would have
      to be within the framework of medical and sociopsychological counselling.

PMID- 17225988
TI  - [Genetic diagnostics as a legislation project. Regulatory initiatives and main
      areas of regulation].
AB  - The legislation project of a law on genetic diagnostics appears to have come to a
      standstill; however, it should be taken up again. The national and international
      discussion underlines the need for regulation. This assessment is based on the
      dynamic developments in the field of biological and medical sciences and the
      resulting problems for medical practice, the healthcare system, commercial in
      terests and, not least, patients, volunteers and clients. The German legislators
      cannot only build on the preparatory work of political advisory institutions and
      commissions; besides current legislation in neighbouring countries, several
      regulatory drafts have been prepared in Germany, which provide important
      normative material for legislative work. However, these drafts also reflect the
      conflicts of interest and assessment arising from such a project. Legislation on
      genetic diagnostics is not only concerned with differing focal points of
      regulation and numerous questions of detail but also with decisions on
      fundamental normative orientations and principles of regulation.

PMID- 17225989
TI  - [Public Health Genomics. The integration of genome-based knowledge into public
      health research, policies and health services].
AB  - Which consequences can be drawn from genome-based knowledge and how can it be
      responsibly and timely translated into policies and practice? What are recent
      developments in genetics and molecular biology, what are the challenges, what are
      the risks of these developments? Which policies can provide an acceptable balance
      between providing strong protection of individuals'interests and needs while
      enabling society to benefit from the genomic advances and empowering individuals?
      How can molecular medicine contribute to more effective and efficient health care
      services, and what infrastructures and policies can already now be implemented to
      assure a benefit for population health? Thus, Public Health Genomics (PHG) tries
      to answer these challenging questions. This integration of genomics into the aims
      of public health is called Public Health Genomics (PHG) and is defined as "the
      responsible and effective translation of genome-based knowledge and technologies
      into public policy and health services for the benefit of population health".

PMID- 17225990
TI  - Detection and incidence of drug-induced agranulocytosis in hospital: a
      prospective analysis from laboratory signals.
AB  - AIMS: Our objectives were to assess the detection and incidence of drug-induced
      agranulocytosis in two university hospitals using hematology laboratory data.
      METHODS: A prospective study was undertaken at Toulouse University Hospital
      (France) and Navarra University Hospital (Spain) for 1 year (from 1 May 2004 to
      30 April 2005). Using a computerized process and hematology laboratory data, all
      neutrophil counts with a value less than 500/mm(3) were registered, allowing
      identification of inpatients suffering from agranulocytosis during the period of
      the study. Medical records of all selected patients were then consulted.
      Cytostatic drugs were excluded from this study. RESULTS: During the period of the
      study, 225,659 neutrophil counts were performed in both hospitals, of which 2,835
      (1.26%) had a neutrophil count less than 500/mm(3), corresponding to 739
      patients. Seventeen patients were excluded because of lack of data, and 20 cases
      of infants younger than 3 months were excluded. Among the remaining patients (n =
      702), 23 cases of drug-induced agranulocytosis (excluding cytostatic drugs) were
      suspected. All cases were classified as "serious" since they led to death in 2
      cases, hospitalization or prolongation of hospitalization in 19 cases and
      threatening of vital prognosis in 2 cases. Withdrawal of suspected drugs was done
      in all cases with regression of neutropenia in 21 cases. According to
      hospitalization data, the annual incidence of drug-induced agranulocytosis was
      1.62 (1.0-2.6) per 10,000 inpatients in Toulouse University hospital (based on
      534 cases) and 3.24 (0.9-8.3) per 10,000 inpatients in Navarra University
      Hospital (based on 168 cases). The involved drugs were mainly antibacterial
      (30.4%), immunosuppressive (17.4%), antithyroid (13.0%), antiplatelet (8.7%) and
      nonsteroidal anti-inflammatory (8.7%) ones. Only seven cases from Toulouse
      University Hospital were spontaneously reported by physicians during the same
      period. Thus, the underreporting coefficient (U) was 2.71 (63.2%) in France.
      CONCLUSION: Our survey allowed us to identify the suspected drug-induced
      agranulocytosis through a prospective study in a large sample of inpatients using
      only laboratory data analysis. We also note an important underreporting rate of
      this serious adverse drug reaction (ADR) to the official French pharmacovigilance
      system. Laboratory data analysis could be used for identifying serious ADRs.

PMID- 17225991
TI  - Antipsychotic-induced extrapyramidal symptoms in patients with schizophrenia:
      associations with dopamine and serotonin receptor and transporter polymorphisms.
AB  - BACKGROUND: Little is known about the influence of polymorphisms of the dopamine
      and serotonin system on the risk for extrapyramidal symptoms (EPS) during
      treatment with antipsychotic drugs. METHODS: Of 119 subjects with schizophrenia
      treated with antipsychotics, 63 had current or previous EPS (acute dystonia,
      parkinsonism, tardive dyskinesia), and 56 had no such symptoms. All subjects were
      genotyped for a total of eight dopamine and serotonin receptor and transporter
      polymorphisms: the Taq1A polymorphism of the dopamine D(2) receptor (DRD2) gene,
      the Msc1 polymorphism of the dopamine D(3) receptor (DRD3) gene, the variable
      number of tandem repeat (VNTR) polymorphism of the dopamine transporter (DAT1)
      gene, four polymorphisms (102T/C, His452Tyr, 516 C/T, and Thr25Asn) of the
      serotonin 5-HT(2A) receptor (5HTR2A) gene, and the 5HTTLPR polymorphism of the
      serotonin transporter (5HTT) gene. RESULTS: The frequency of the A1 allele of the
      DRD2 Taq1A polymorphism was significantly higher in the EPS group than in the
      control group [16% vs. 7%, P = 0.040; odds ratio (OR) 2.4; 95% confidence
      interval (CI) 1.1-5.7]. Also, the 9 repeat allele of the DAT1 VNTR polymorphism
      was significantly more common in the EPS group (42% vs. 28%, P = 0.030; OR 1.9;
      95% CI 1.1-3.3). Being a carrier of both DRD2 Taq1A A1 and DAT1 VNTR 9 repeat
      alleles was also significantly associated with the occurrence of EPS (19% vs. 6%,
      P = 0.040; OR 4.0; 95% CI 1.05-15.2) No significant differences in allele
      frequencies were found for the other polymorphisms. CONCLUSION: Presence of the
      Taq1A A1 allele of the DRD2 and the 9 repeat allele of the DAT1 VNTR
      polymorphisms might be risk factors for EPS caused by antipsychotic drugs.

PMID- 17225992
TI  - A fermentation system designed to independently evaluate mixing and/or oxygen
      tension effects in microbial processes: development, application and performance.
AB  - In order to evaluate the independent effects of hydrodynamic conditions and/or
      oxygen tension on culture physiology and productivity, a fermentation system
      designed to control dissolved oxygen at constant power drawn (P/V) was developed.
      The system included a fully instrumented 14 l bioreactor coupled to a PC for data
      acquisition and control. Power drawn was measured (using a commercial torquemeter
      coupled to the shaft) and maintained constant by varying the agitation speed;
      while gas blending was used to control dissolved oxygen concentration. To
      validate the system, rheological-complex fermentations involving xanthan gum
      production and filamentous fungal cultivation (using Xanthomonas campestris and
      Trichoderma harzianum) were developed. In both cases, and despite the changing
      environmental conditions (due to increased broth viscosities and microbial
      respiration), both variables were controlled at the desired set points. Through
      such a system, a rigorous evaluation of the hydrodynamic conditions and/or oxygen
      tension on culture physiology and productivity is now feasible.

PMID- 17225994
TI  - Short-cut nitrification of domestic wastewater in a pilot-scale A/O nitrogen
      removal plant.
AB  - The feasibility of nitrite accumulation in a pilot-scale A/O (anoxic/oxic)
      nitrogen removal plant treating domestic wastewater was investigated at various
      dissolved oxygen (DO) concentrations and pH levels. The results showed that the
      pH was not a useful operational parameter to realize nitrite accumulation.
      Significant nitrite accumulation was observed at the low DO concentration range
      of 0.3-0.8 mg/l and the maximum nitrite accumulation ratio of about 90% occurred
      at a DO concentration of 0.6 mg/l. This suggests a reduction of 22% in the oxygen
      consumption, and therefore a considerable saving in aeration. However, the
      nitrite accumulation was destroyed at the high DO concentration and the
      resumption was very slow. In addition, the average ammonia removal efficiency
      reached as high as 93% at the low DO level. Moreover, experimental results
      indicated that nitrogen could be removed by simultaneous nitrification and
      denitrification (SND) via nitrite in the aerobic zones at the low DO
      concentration, with the efficiency of 6-12%.

PMID- 17225993
TI  - Novel bioconversion of wheat straw to bio-organic fertilizer in a solid-state
      bioreactor.
AB  - In order to increase the eco-efficiency and overall availability of naturally
      renewable resource, the novel bioconversion of steam-exploded wheat straw to bio
      organic fertilizer containing N(2)-fixer, P and K solubilizers was investigated.
      The conversion was performed in solid-state fermentation (SSF) with periodic air
      forced pressure oscillation (PAPO). The results showed that SSF-PAPO was
      competitive with the conventional solid-state fermentation (cSSF) in biomass
      accumulation and wheat straw digestion. With solid-liquid ratio 1:3, microbial
      biomass production at 72 h was high up to 2 x 10(11) cfu g(-1), nearly twice as
      that in cSSF. The degradation rate of cellulose, hemicellulose and lignin after
      fermentation in SSF-PAPO reached 48.57 +/- 10.66, 84.77 +/- 2.75 and 2.15 +/-
      10.11, respectively, which was greater than that of 29.30 +/- 10.28%, 33.47 +/-
      4.85% and 0.53 +/- 9.07% in cSSF, correspondingly. The SSF-PAPO system displayed
      unique advantage, by a novel gas phase control strategy on gas concentration and
      heat gradient, on the bioconversion of wheat straw to the bio-organic fertilizer.

PMID- 17225995
TI  - Carotid angioplasty and stent placement for restenosis after endarterectomy.
AB  - INTRODUCTION: Recurrent carotid stenosis following endarterectomy is a common
      complication, and reoperation may be associated with increased morbidity. The
      goal of this study was to determine the procedural safety and long-term
      complication rates of carotid angioplasty and stenting for recurrent stenosis.
      METHODS: Of 248 consecutive carotid angioplasty and/or stenting procedures
      performed at our institution between March 1996 and November 2005, 83 procedures
      for recurrent stenosis following endarterectomy were performed in 75 patients
      (mean age 68 years; 43 men, 32 women) without cerebral protection devices. The
      patients' medical records were retrospectively reviewed for vascular imaging
      reports and available clinical follow-up. Procedural and long-term complication
      rates were calculated. RESULTS: Recurrent stenosis was reduced from a mean of
      80.6% to no significant stenosis in 82 of 83 procedures. The procedural stroke
      rate was 3 out of 83 procedures (3.6%). The procedural transient ischemic attack
      (TIA) rate was 2 out of 83 procedures (2.4%). Mean follow-up was 22.4 months
      (range 0.1 to 86.7 months) with at least 6 months follow-up for 54 of 83
      procedures (65%). There were five TIAs and no strokes on follow-up (new TIAs at
      25.5 and 43.4 months; recurrent TIAs at 1, 11.1, and 12 months, all with normal
      angiograms). The composite 30-day stroke, myocardial infarction, or death rate
      was 5 of 83 procedures (6.0%). CONCLUSION: In this series, angioplasty and
      stenting were effective in relieving stenosis secondary to recurrent carotid
      disease after endarterectomy, and have low rates of ischemic complications.

PMID- 17225997
TI  - New strategies to screen for endocrine-disrupting chemicals in the Portuguese
      marine environment utilizing large volume injection-capillary gas chromatography
      mass spectrometry combined with retention time locking libraries (LVI-GC-MS-RTL).
AB  - A new analytical strategy to screen for endocrine-disrupting chemicals (EDCs) in
      environmental matrices is presented. The strategy uses solid-phase extraction
      followed by large volume injection and capillary gas chromatography coupled to
      mass spectrometry combined with retention time locking libraries (SPE-LVI-GC-MS
      RTL). Characterization of the proposed methodology (SPE-LVI-GC-MS) for selected
      classes of EDCs enabled high reproducibility and robustness at the ultratrace
      level. The RTL databases used allowed hundreds of non-target semivolatiles (i.e.,
      pesticides, polycyclic aromatic hydrocarbons, polychlorinated biphenyls and other
      classes of suspected EDCs from a great number of unknown environmental matrices)
      to be simultaneously screened for in an easy, fast and remarkable manner. The
      application of the proposed methodology to real environmental samples
      demonstrated its remarkable selectivity and sensitivity at the ultratrace level.
      Screening assessments performed on water and sediment matrices from eight
      Portuguese estuaries and coastal waters identified EDC "hotspots." These EDCs
      mainly come from agricultural and a wide variety of industrial sources, and
      include pesticides and pesticide metabolites, phenolic derivatives and polycyclic
      aromatic hydrocarbons, which are included in the lists of priority substances
      published by international environmental agencies. The estuaries that contained
      relatively high levels of pesticides were Guadiana, Sado and Mondego, while
      Minho, Douro and Formosa showed enhanced levels of phenolic derivatives.
      Dibutyltin and tributyltin, selected as target compounds to be monitored by SPE
      LVI-GC-MS in the selected ion monitoring mode, were shown to be widespread
      contaminants at trace levels in almost all of the sediment matrices assessed. The
      reliability of the proposed methodology undoubtedly makes it a valuable tool that
      could replace other analytical strategies currently used to screen for EDCs
      present in the environment at ultratrace levels.

PMID- 17225998
TI  - Teaching surface characterization to undergraduates.

PMID- 17225996
TI  - New noncellular fluorescence microplate screening assay for scavenging activity
      against singlet oxygen.
AB  - In the present study, a new fluorescence microplate screening assay for
      evaluating scavenging activity against singlet oxygen (1O2) was implemented. The
      chemical generation of 1O2 was promoted using the thermodissociable endoperoxide
      of disodium 3,3'-(1,4-naphthalene)bispropionate (NDPO2). The detection of 1O2 was
      achieved using dihydrorhodamine 123 (DHR), a nonfluorescent molecule that is
      oxidizable to the fluorescent form rhodamine 123 (RH). The combined use of a 1O2
      selective generator and a highly sensitive probe (DHR) was then successfully
      applied to perform a screening assay of the 1O2 scavenging activities of ascorbic
      acid, penicillamine, cysteine, N-acetylcysteine (NAC), methionine, reduced
      glutathione (GSH), dihydrolipoic acid, lipoic acid, and sodium azide. All of
      these antioxidants exhibited concentration-dependent 1O2 scavenging capacities.
      They could be ranked according to observed activity: ascorbic
      acid>cysteine>penicillamine>dihydrolipoic acid>GSH>NAC>sodium azide>lipoic acid
      (IC50 values of 3.0+/-0.2, 8.0+/-0.7, 10.9+/-0.8, 25.2+/-4.5, 57.4+/-5.9, 138+/
      13, 1124+/-128, 2775+/-359 microM, mean+/-SEM, respectively)>methionine (35% of
      scavenging effect at 10 mM). In conclusion, the use of NDPO2 as a selective
      generator for 1O2 and its fluorescence detection by the highly sensitive probe
      DHR is shown to be a reliable and resourceful analytical alternative means to
      implement a microplate screening assay for scavenging activity against 1O2.

PMID- 17225999
TI  - Behaviour of semipermeable membrane devices in neutral pesticide uptake from
      waters.
AB  - The application of semipermeable membrane devices (SPMDs) has been evaluated as a
      passive sampler for the collection of multiresidue pesticides in continental
      waters. Seven chlorinated, five organophosphorus, six carbamate, nine pyrethroid
      and ten other pesticides were tested in order to estimate which compounds can be
      retained with these devices. The effect of water parameters, such as temperature,
      pH, ionic strength and organic matter content, were evaluated for their effect on
      the retention of the pesticides by the SPMDs. Studies of uptake from water were
      performed in a glass beaker containing 2 L distilled water spiked with 50 ng L-1
      of each pesticide investigated. A SPMD was put in the beaker, under turbulent
      conditions, and analysed after 2 days' extraction. The contents of each SPMD were
      microwave-assisted-extracted twice with 30 mL hexane-acetone, to 90 degrees C for
      10 min, and this was followed by a cleanup based on acetonitrile partitioning and
      solid-phase extraction. Gas chromatography with tandem mass spectrometry
      detection was employed for determination of pesticides, and provided low limits
      of detection from 0.5 to 7 ng per SPMD. Higher absorption rates were observed for
      pyrethroid, organophosphorus and chlorinated compounds than for carbamates.
      Pesticide uptake rates were independent of the water composition and decreased at
      low temperature.

PMID- 17226001
TI  - Spectrofluorimetric determination of trace amounts of coenzyme A using a terbium
      ion-ciprofloxacin complex probe in the presence of periodic acid.
AB  - A new spectrofluorimetric method was developed for the determination of trace
      amounts of coenzyme A (CoA). In the presence of periodic acid (H5IO6), CoA can
      remarkably enhance the fluorescence intensity of the Tb3+-ciprofloxacin (CIP)
      complex at 545 nm in a buffer solution at pH 5.4; the enhanced fluorescence
      intensity of the Tb3+ ion is proportional to the concentration of CoA. The
      optimal conditions for the determination of CoA were also investigated. The
      linear range and the detection limit for the determination of CoA were 6.08x10(
      6)-1.64x10(-5) and 2.1x10(-8) mol L-1, respectively. This method is simple,
      practical and relatively free of interference from coexisting substances, and can
      be successfully applied to assess CoA in injection and biological samples.
      Moreover, the enhancement mechanism of the fluorescence intensity of the CoA-Tb3+
      CIP system in the presence of H5IO6 is also discussed.

PMID- 17226002
TI  - New hexamethine-hemicyanine dyes for the development of integrated optochemical
      sensors.
AB  - New far-visible absorbing anilino-cyanine dyes have been synthesised for future
      application as chromoionophores in integrated waveguide absorbance optodes based
      on bulk optodes. The effect of the heterocycle, of the substitution of the
      heterocyclic nitrogen and of the type of heptamethine central ring on the pKa
      values (4.3-8.2 in ethanol-water solutions and 9.5-11.0 in plasticised PVC
      membranes), on the spectroscopic characteristics of the dye and on photostability
      is discussed. pH-selective bulk optodes have been formulated as a first approach
      to develop ion-selective optodes, and sensitivity, repeatability, lifetime and
      response time have been determined. The dyes show good analytical behaviour for
      use as chromoionophores for the development of ion-selective optodes. Reversible
      (80-87%), fast (tr90%=0.94-2.28 min) and pH-sensitive membranes (slopes of 0.09
      0.23 DeltaAbs.pHdec-1, absorbance range 0.19-0.53) have been obtained. Moreover,
      they exhibit good spectroscopic features for employment with integrated
      optochemical sensors: absorption maxima of the acidic species in plasticised PVC
      membranes matched those of 650-670-nm LEDs, high molar absorption coefficients
      (epsilonacidic=3.5x10(4)-9.3x10(4) L mol-1 cm-1 and epsilonbasic=1.9x10(4)
      6.7x10(4) L mol-1 cm-1) and fluorescence.

PMID- 17226003
TI  - Solution to quality assurance challenge 4.

PMID- 17226004
TI  - Use of chemometric and geostatistical methods to evaluate pesticide pollution in
      the irrigation and drainage channels of the Ebro river delta during the rice
      growing season.
AB  - Data sets obtained from quantitative analysis of seventeen pesticides in water
      samples from a network of irrigation and drainage channels in the Ebro river
      delta (Catalonia, NE Spain) have been analysed by chemometric and geostatistical
      methods. Samples were taken at fourteen locations during the main rice-growing
      season, from May to August 2005. Principal-component analysis enabled
      investigation of the spatial and temporal distribution of the main pollution
      patterns caused by application of pesticides in the region under study. A first
      pesticide-contamination pattern from the Ebro river was differentiated from a
      second more specific pattern from the water-drainage channels of the delta,
      collected from the rice fields. The seasonal peak in this more specific rice
      pesticide source was observed in July. Coupling the results from chemometric data
      analysis with use of geostatistical methods was shown to be a useful procedure
      for discovery of the most significant spatial and monthly variations of the main
      pesticide-contamination patterns, taking into account the particular geographical
      structure of the area under study.

PMID- 17226005
TI  - Sum frequency generation spectroscopic study of the condensation effect of
      cholesterol on a lipid monolayer.
AB  - Sum frequency generation (SFG) spectra and surface pressure-molecular area (pi-A)
      isotherms have been obtained for mixed cholesterol-DPPC monolayers with
      cholesterol mole fractions, x(chol.), from 0 to 1.0, at the air-water interface,
      under same conditions, at 22 degrees C. Analysis of the spectra indicated that
      incorporation of cholesterol into the monolayers at 3 mN m-1 greatly increases
      the conformational and orientational order of the alkyl chains of DPPC,
      maximizing these properties at x(chol.)=0.4. Analysis also indicated that order
      in the mixed monolayers at 15 and 35 mN m-1 is not affected by incorporation of
      cholesterol. The pi-A isotherms measured at 3 mN m-1 for the mixed monolayer with
      x(chol.)=0.4 have the largest negative deviation of the molecular area relative
      to those of ideal mixtures (the so-called "condensation effect" of cholesterol),
      indicating the most thermodynamically stable state. Comparison of results from
      SFG spectra and pi-A isotherms explicitly proved that the condensation effect can
      be interpreted in terms of conformational and orientational ordering of the alkyl
      chains of DPPC.

PMID- 17226006
TI  - [Liposuction curettage versus Botox for axillary hyperhidrosis. A prospective
      study of the quality of life].
AB  - BACKGROUND: Axillary hyperhidrosis is a dysfunction of the secretion of sweat
      glands. Conservative treatment modalities are mostly ineffective. Liposuction
      combined with subcutaneous curettage (TLC) destroys the sweat glands, while Botox
      injections inhibit the cholinergic transmission. MATERIAL AND METHOD: Of a total
      of 88 patients, TLC was carried out in 47 and 41 patients received intradermal
      Botox injections. The effect of both forms of treatment on the quality of life
      was assessed using a specific hyperhidrosis questionnaire and was correlated with
      sweat volumes measured by gravimetry. RESULTS: Follow-up after 6 months showed
      significantly changed sweat volumes of 52+/-41 mg/min of TLC patients versus 78+/
      87 mg/min in the Botox group. In the TLC group 91% and in the Botox group 98%
      were satisfied with the result. CONCLUSION: The stress of a single surgical
      intervention is to be weighed against the necessary repetitive application of
      multiple Botox injections. Both methods are superior to other, more radical
      surgical methods in terms of efficacy and complication rates. Botox and TLC lead
      to a significant improvement of the quality of life.

PMID- 17226008
TI  - [Therapy with entecavir in chronic hepatitis B. BEHoLD-Study (Benefits of
      Entecavir for Hepatitis B Liver Disease)].

PMID- 17226007
TI  - [Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis].
AB  - Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis
      (NASH) are the hepatic manifestations of the metabolic syndrome. Since the
      prevalence of obesity and consequently of the metabolic syndrome is steadily
      increasing, the different types of NAFLD are nowadays the most common cause of
      liver injury in North America. The development of NASH and fatty liver cirrhosis
      occurs after a "two-hit-theory", in which hepatic steatosis is followed by lipid
      peroxidation, the production of cytokines and the induction of Fas ligand. A
      standardized drug based therapy does not exist so far, but glitazones have
      emerged as a promising treatment option. However, since the disease is related to
      Western lifestyle, treatment should be based on prevention and changes in
      lifestyle.

PMID- 17226009
TI  - [History and definition(s) of metabolic syndrome].
AB  - Metabolic syndrome--a cluster of metabolic diseases and hypertension--is not a
      new disease. It has been present in the upper classes of all highly developed
      cultures suffering from over-nutrition and limited physical activity. In the
      medical literature, it can be found in Renaissance and Baroque times. We are
      presently experiencing a global tsunami of this syndrome as over-nutrition and
      lack of movement are typical for large groups of the population. The current
      definition of metabolic syndrome of the American Heart Association/National
      Heart, Lung and Blood Institute and the International Diabetes Federation
      incorporates the quartet central obesity, hypertension, increased blood sugar and
      dyslipidemia (hypertriglyceridemia, low HDL cholesterol). Thus, simple,
      collective diagnostics and therapy for this finely meshed group of diseases
      together with its risk factors is possible.

PMID- 17226010
TI  - [The heart in rheumatic diseases].
AB  - As systemic immunological disorders inflammatory rheumatic diseases potentially
      involve organs and structures beyond the musculo-skeletal system including skin
      and blood vessels. Various neurological, renal, pulmonary, hematological and
      cardiac manifestations contribute to the broad clinical picture of connective
      tissue diseases and vasculitides. Regarding cardiac disease all structures of the
      heart may be affected. Pericarditis in lupus, mitral valve changes in the
      antiphospholipid syndrome, myocarditis and coronary artery stenosis in the
      systemic vasculitides are typical examples in systemic rheumatic diseases. Beyond
      this, pulmonary hypertension in systemic sclerosis or congenital heart block in
      newborns of lupus patients are further cardiac issues. Since better treatment
      options led to more long-lasting courses in connective tissue diseases,
      cardiovascular complications as a consequence of chronic disease- and therapy
      related damage gain increasing attention.

PMID- 17226012
TI  - [The early history of transmissible spongiform encephalopathies exemplified by
      scrapie].
AB  - Transmissible spongiform encephalopathies (TSE) are unique diseases in that they
      are sporadic, hereditary, and infectious. The transmissible pathogen--the prion-
      stands out from all other pathogens in being devoid of nucleic acids. Instead its
      most important and possibly only constituent is a host-encoded protein, the prion
      protein (PrP), in an alternative conformation induced by post-translational
      modifications. Thus TSEs belong to and are so far the only transmissible member
      of the continuously growing group of disorders collectively referred to as
      protein conformational disorders. During elucidation of these disorders, many
      different--and contradictory--theories have been put forward. Early researchers,
      mostly driven by the economic effect of these diseases upon sheep farming,
      engaged in heavy disputes concerning the heredity vs infectivity of scrapie.
      After the experimental demonstration of scrapie's infectivity during the
      twentieth century, research focused on elucidating the nature of the
      transmissible agent. The current work comprehensively summarizes the early
      literature available on TSE research.

PMID- 17226011
TI  - [Polycystic ovary syndrome. Prototype of a cardio-metabolic syndrome].
AB  - Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women
      in the reproductive age and is a major cause of anovulation, hyperandrogenism and
      infertility. Since obesity and insulin resistance are predominant features of
      women with PCOS, a variety of metabolic disturbances are associated. There is a
      marked increase in the risk of developing type-2 diabetes in these patients and a
      majority of women with PCOS will subsequently harbour an enhanced cardiovascular
      risk.

PMID- 17226013
TI  - [Cerebral lymphomatoid granulomatosis. A case report].
AB  - We present the case of a 57-year-old patient who was admitted with fever and
      disorientation. The cerebrospinal fluid showed a mild pleocytosis and increased
      protein content. MR imaging revealed multiple lesions, particularly in the
      subcortical white matter, with spot like central contrast enhancement. The
      diagnosis of lymphomatoid granulomatosis was finally made through open lung
      biopsy. Despite treatment with rituximab and, in the later course of the disease,
      additionally with cyclophosphamide, the patient died 3 months after the diagnosis
      was made.

PMID- 17226014
TI  - [Myoclonus].
AB  - Myoclonus, an involuntary movement disorder reveals itself with a wide variety of
      short muscle twitches or jerks, and may cause severe disability. From a clinical
      perspective, it is sometimes difficult to discriminate myoclonus from other
      central movement disorders. Moreover, myoclonus has a spectrum of causes
      including rare neurological syndromes and uncommon manifestations of systemic
      disease. Its pathogenesis is only partially understood. Neurophysiologic
      investigations suggest a close relationship between certain types of myoclonic
      jerking and epilepsy. The use of anticonvulsants for treatment of myoclonus has
      its basis in such observations and empirical evidence. Often high doses or a
      combination of drugs, or both are required, with, however, serious side effects.

PMID- 17226016
TI  - MR imaging of spinal trauma.
AB  - Magnetic resonance (MR) imaging plays an increasingly important role in
      evaluation of the patient who has sustained spinal trauma. This review discusses
      the role of MR imaging relative to plain radiographs and computed tomography in
      the evaluation of the patient with spinal trauma and presents a method for
      systematic review of MR images for assessing spinal injury.

PMID- 17226017
TI  - Contrast reaction from hip arthrogram.
AB  - Arthrography is considered a safe procedure with rare reactions to intra
      articular contrast administration. Although the use of intra-articular contrast
      carries a small risk of reaction, no prior serious complications had been
      encountered in our experience with arthrography. We report a patient's prolonged
      reaction to contrast media after an arthrogram of the hip. Literature review
      demonstrated no prior report of contrast media reactions to hip arthrography.
      Therefore, we decided to review the literature and report our case.

PMID- 17226015
TI  - Embolization for a bleeding pelvic fracture in a patient with persistent sciatic
      artery.
AB  - Emergency embolization for a bleeding pelvic fracture was performed in a patient
      with persistent sciatic artery, a rare anatomic variation in which the internal
      iliac artery continues to the popliteal artery. Successful hemostasis was
      achieved without complications by means of selective catheterization into each
      branch of the internal iliac artery. Awareness of this unusual vascular anatomy
      is critically important to avoid serious complication of emergency embolization.

PMID- 17226018
TI  - Traumatic abdominal aortic injury treated by endovascular stent placement.
AB  - Traumatic injury of the abdominal aorta is rare and potentially lethal. The
      authors present the case of a restrained passenger who was involved in a high
      speed, head-on motor vehicle accident. On arrival in the emergency department,
      the patient complained of abdominal pain, was tachycardic and had a large
      ecchymoses on his right flank and lower abdominal wall. Computed tomography (CT)
      angiography (CTA) of the abdomen revealed a degloving injury to the abdominal
      wall, small bowel injury, and a distal abdominal aortic injury with a small
      amount of retroperitoneal hemorrhage. The patient underwent surgical repair of
      bowel injuries and the anterior abdominal wall. Because of risk of peritoneal
      soiling, open repair of the aorta was not attempted. The interventional radiology
      and vascular surgery services performed an endovascular repair of the aortic
      injury using a bifurcated endograft.

PMID- 17226019
TI  - Chorioretinal anastomosis and photodynamic therapy: a two-year follow-up study.
AB  - BACKGROUND: To evaluate the two-year efficacy of photodynamic therapy with
      Visudyne (PDT) in neovascular age-related macular degeneration (AMD) eyes with
      chorioretinal anastomosis (CRA). METHODS: A non-randomized, institutional,
      prospective study, of 28 consecutive eyes of 23 patients, with CRA, treated with
      PDT. Masked best corrected visual acuity (VA) and angiographic features at
      baseline and during the period of two years were evaluated. RESULTS: Twenty eight
      eyes completed one year and 19 eyes completed two years of follow-up. The number
      of treatments was 3 in the first year, and 0.8 in the second year. A VA loss < 3
      lines occurred in 53% of the eyes, at two years. Treated eyes lost 0.5 lines in
      the first year and 2.4 lines in the second (p < 0.01). Recurrence with additional
      significant VA loss occurred in four eyes (21%) during the second year. Fourteen
      eyes (74%) showed no fluorescein leakage at two years. CONCLUSION: AMD eyes with
      chorioretinal anastomosis can benefit from PDT with Verteporfin at two years.
      However, during the second year significant additional VA loss occurs mainly due
      to recurrence. New modalities of treatment are necessary to achieve VA
      improvement in CRA eyes.

PMID- 17226021
TI  - Enlargement of optic nerve resembling orbital mass in case of optic neuritis.

PMID- 17226020
TI  - Alterations of amino acids and glutamate transport in the DBA/2J mouse retina;
      possible clues to degeneration.
AB  - BACKGROUND: The DBA/2J mouse spontaneously develops ocular hypertension and time
      dependent progressive retinal ganglion cell (RGC) loss. This study examines
      changes in amino acid levels in the vitreous, and changes in the expression of
      retinal glutamate transporters and receptors that occur during the progression of
      this pathology. METHODS: Retinas were obtained from DBA/2J mice at ages 3, 6 and
      11 months. C57BL/6 mice were used as age-matched controls. Vitreal amino acid
      content was measured with HPLC. Western blotting and immunohistochemistry were
      performed using specific antibodies against the glutamate transporters (GLAST,
      GLT-1v, EAAC-1) and glutamate receptors, particularly NMDA (NR1, NR2A, NR2B) and
      AMPA (GluR1, GluR2/3, GluR4) receptors. RESULTS: HPLC showed retinal
      concentrations of glutamate, glutamine, glycine, alanine, lysine, serine, and
      arginine to be significantly higher in DBA/2J mice at 11 months of age compared
      to age-matched controls. Western Blots revealed a moderate decrease of GLAST and
      GLT-1v expression in DBA/2J mice at 6 and 11 months as compared to age-matched
      controls while there was no change in EAAC1. Immunohistochemically, no changes in
      expression of NMDA and AMPA receptors were seen. CONCLUSION: Alterations of amino
      acid content and enhanced glutamate neurotransmission might be involved in the
      pathogenesis of retinal neurodegeneration in the DBA/ 2J mouse model of ocular
      hypertension. Moreover, these mice provide an animal model for studying
      excitotoxic retinal damage.

PMID- 17226022
TI  - Plasma endothelin-1 levels depress optic nerve head circulation detected during
      the glucose tolerance test.
AB  - PURPOSE: To determine the relationship between the changes in optic nerve head
      (ONH) circulation and the level of plasma endothelin-1 (ET-1) during the glucose
      tolerance test (GTT). METHODS: Twenty-six healthy volunteers with normal GTT and
      15 patients with mild hyperglycemia and abnormal GTT were studied. The ONH
      circulation [square blur rate (SBR) value], blood pressure, intraocular pressure
      (IOP), blood glucose, blood insulin and plasma ET-1 were determined before and
      every hour up to 3 h after an oral intake of 75 g of glucose. RESULTS: The SBR
      increased in the normal glucose tolerance group at all times during the GTT, but
      it decreased significantly in the abnormal glucose tolerance group (P < 0.05).
      Before the GTT, the plasma ET-1 level was not significantly different in the two
      groups; however, the level increased 1 h after the oral GTT in the abnormal
      glucose tolerance group (P < 0.05). No significant changes were observed in mean
      blood pressure or IOP. CONCLUSIONS: ONH circulation increased after glucose
      intake in the normal glucose tolerance group and remained high even after the
      blood glucose level had returned to its baseline. The decrease in ONH circulation
      in the abnormal glucose tolerance group was attributed partly to the increased ET
      1.

PMID- 17226024
TI  - Prevalence of ocular manifestations in hereditary hemorrhagic telangiectasia.
AB  - BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a systemic disorder of
      the fibrovascular tissue. Few data have been published on the frequency of
      ophthalmologic manifestations. The aim of this study was to assess this
      frequency. METHODS: A prospective observational cross-sectional study was
      conducted in a multitude of clinical practices and in a tertiary referral center.
      The main outcome measure was the number of vascular malformations detected by an
      ophthalmologic inspection of the retina and the conjunctivae in both eyes in a
      random sample of patients with HHT. RESULTS: No retinal telangiectases were
      observed in any of the 75 patients (150 eyes) examined. Conjunctival
      telangiectases were detected in 28 of 74 patients (47 of 148 eyes). CONCLUSIONS:
      The prevalence of retinal telangiectases seems to be lower than 1/75 (< 1.3%).
      This data does not justify screening procedures to detect retinal telangiectases.
      Ophthalmologists should be aware of the symptoms of HHT and its systemic
      character.

PMID- 17226023
TI  - Anti-adenoviral effect of anti-HIV agents in vitro in serotypes inducing
      keratoconjunctivitis.
AB  - BACKGROUND: Around one million people are affected by adenoviral
      keratoconjunctivitis a year in Japan, and it is recognized as one of the major
      pathogens of ophthalmological nosocomial infection worldwide. Although cidofovir
      can be used systemically for immunocompromised patients with disseminated
      adenoviral infection, no specific anti-adenoviral agent has been established for
      the treatment of adenoviral infection. We evaluated the anti-adenoviral effect of
      anti-HIV (human immunodeficiency virus) agents in this study. METHODS: Five anti
      HIV agents (zalcitabine, stavudine, nevirapine, indinavir and amprenavir) were
      subjected to in vitro evaluation. A549 cells were used for viral cell culture,
      and adenovirus serotypes 3, 4, 8, 19 and 37 were used. After calculating CC(50)
      (50% cytotoxic concentration) of each agent by MTS (3-(4,5-dimethylthiazol-2-yl)
      5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) method, we cultured
      adenovirus with the agents for seven days and quantitatively measured extracted
      adenoviral DNA by real-time PCR. RESULTS: Among the anti-HIV drugs, zalcitabine
      and stavudine, both nucleoside reverse transcriptase inhibitors, showed
      significant anti-adenoviral activity. In contrast, nevirapine, a non-nucleoside
      reverse transcriptase inhibitor, and indinavir and amprenavir, which are both
      protease inhibitors, were ineffective against adenovirus. CONCLUSIONS: These
      results indicate that zalcitabine and stavudine are possible candidates for the
      local and systemic treatment of adenoviral infection, and the anti-adenoviral
      effect might depend on the pharmacological properties of anti-HIV agents. The
      chemical properties on the clinical safety for systemic and local application
      need to be determined in order to for these drugs to be accepted for the
      treatment of adenovirus in clinical settings.

PMID- 17226025
TI  - Intravitreal triamcinolone acetonide in the management of cystoid macular edema
      in Behcet's disease.
AB  - PURPOSE: To determine the efficacy of intravitreal triamcinolone acetonide (ivTA)
      injection in the management of cystoid macular edema (CME) due to uveitis in
      patients with Behcet's disease. METHODS: Ten eyes of seven patients with CME
      associated with Behcet's disease were included in the study. A quantity of 4 mg
      of triamcinolone acetonide was injected intravitreally in all of the eyes. The
      maculas of the patients were evaluated with optical coherence tomography (OCT)
      and fluorescein angiography (FA). The change in visual acuity, fluorescein
      leakage, macular thickness, and potential complications were assessed. RESULTS:
      The mean follow-up was 15.6 months (range 7-19 months). There was an increase of
      more than two Snellen lines in the visual acuity in seven of the ten eyes (70%)
      at the last examination. Macular edema regressed completely in eight of the ten
      eyes (80%) at the last visit on OCT and FA. The mean central macular thickness
      assessed by OCT was 406 mum before treatment and 186.9 mum at the last visit. The
      intraocular pressure (IOP) exceeded 21 mmHg in six eyes of five patients (60%)
      during the follow-up. At the last visit, the IOP was less than 21 mmHg in five
      eyes with medication. One eye underwent glaucoma filtration surgery. Four eyes of
      three patients had cataract progression. In four eyes of four patients (40%), a
      second ivTA injection was given due to relapsing CME. CONCLUSION: Intravitreal
      triamcinolone acetonide (ivTA) may be beneficial in the management of CME in
      patients with Behcet's disease. Repeated ivTA injections might be required if CME
      reoccurs.

PMID- 17226027
TI  - A chickpea Kunitz trypsin inhibitor is located in cell wall of elongating
      seedling organs and vascular tissue.
AB  - Kunitz proteinase inhibitors in legumes have mainly been described as defence and
      storage proteins. Here, we report a Kunitz trypsin inhibitor, encoded by the
      CaTPI-1 gene from Cicer arietinum. The transcription of this gene mainly occurs
      in seedling vegetative organs, and is affected by the light and growth stages.
      The recombinant TPI-1 protein expressed in E. coli was seen to be an efficient
      inhibitor of trypsin. After the generation of polyclonal antibodies against
      recombinant TPI-1 protein, the protein was located in the cell wall of elongating
      epicotyls and radicles by Western-blot experiments, in agreement with the
      transcription pattern. These results, together with the fact that both CaTPI-1
      mRNA and protein levels decreased with epicotyl growth, suggest a possible role
      in the elongation of seedling epicotyls and radicles. Immunolocalization analyses
      of the TPI-1 protein indicated that it is abundant in the cell walls of both
      immature primary xylem cells and surrounding parenchyma cells. This location has
      led us to explore potential functions for TPI-1 protein in vascular tissue during
      seedling elongation.

PMID- 17226028
TI  - Systemic signalling in barley through action potentials.
AB  - Using apoplastic voltage- and ion selective microprobes, in barley leaves action
      potentials (APs) have been measured, which propagate acropetally as well as
      basipetally from leaf to leaf or from root to leaf following the application of
      mild salt stress (e.g. 30-50 mM KCl or NH(4)Cl) or amino acids (e.g. 1 mM
      glutamic acid or 5 mM GABA). Voltage changes were biphasic, followed an 'all-or
      none' characteristic, and propagated at 20-30 cm min(-1) irrespective of the
      direction. With the salt-induced APs, a strong initial depolarization is the main
      AP-releasing factor that first causes Ca(2+) influx and then anion efflux. Ca(2+)
      influx coincides with an initial slower depolarization, the rapid anion efflux
      causes the typical voltage 'break-through'. Subsequently, K(+)-efflux starts
      after the depolarizing voltage has passed the K(+) equilibrium potential
      (inversion of the K(+) driving force). Glutamic acid and GABA induce APs not
      through membrane depolarization, but presumably by binding to a putative receptor
      or to ligand-gated Ca(2+)-conducting channels, respectively, followed by Ca(2+)
      induced activation of anion efflux. APs are accompanied by transient apoplastic
      pH increase (about 1 unit), and by cytoplasmic pH decrease (about 0.5 units). The
      apoplastic pH change is interpreted as an indicator of stress, the cytoplasmic pH
      change as a prerequisite for defence related gene activation. Since APs are
      released by agents added in a moderate concentration range, it is suggested that
      they may serve as first and fast systemic signals following attack from
      pathogens.

PMID- 17226026
TI  - Differential expression of phenylpropanoid and related genes in brown-midrib bm1,
      bm2, bm3, and bm4 young near-isogenic maize plants.
AB  - The expression of phenylpropanoid and related genes was investigated in bm1, bm2,
      bm3, and bm4 near-isogenic maize plants at the 4-5 leaf stage using a gene
      specific cell wall macro-array. The bm3 mutant, which is mutated in the caffeic
      acid O-methyltransferase (COMT) gene, exhibited the lowest number of
      differentially expressed genes. Although no other phenylpropanoid gene had an
      altered expression, two distinct OMT and two cytochrome P450 genes were
      overexpressed suggesting the activation of alternative hydroxylation/methylation
      pathways. The bm1 mutant had the highest number of differentially expressed
      genes, all of which were under-expressed. Bm1 mutant plants were affected not
      only in cinnamyl alcohol dehydrogenase (bm1 related CAD) gene expression as
      expected, but also in the expression of other CAD/SAD gene family members and
      several regulatory genes including MYB, ARGONAUTE and HDZip. As originally
      believed, the bm1 mutation could be localized at the CAD locus, but more probably
      in a gene that regulates the expression of the CAD gene family. The profile of
      under-expressed genes in the bm2 mutant is nearly similar to that of bm1. These
      genes fell under several functional categories including phenylpropanoid
      metabolism, transport and trafficking, transcription factors and regulatory
      genes. As the bm2 mutant exhibited a lower guaiacyl (G) unit lignin content, the
      bm2 mutation could affect a regulatory gene involved, perhaps indirectly, in the
      regulation, conjugation or transport of coniferaldehyde, or the establishment of
      G-rich maize tissues. The pattern of gene expression in bm4 plants, characterized
      by the over-expression of phenylpropanoid and methylation genes, suggests that
      the bm4 mutation likely also affects a gene involved in the regulation of
      lignification.

PMID- 17226029
TI  - Characterization of regulatory non-catalytic hexokinases in Aspergillus nidulans.
AB  - Hexokinases catalyse the first step in glucose metabolism and play a role in
      glucose sensing in mammals, plants and fungi. We describe a new class of
      hexokinases that appear to be solely regulatory in function. The Aspergillus
      nidulans hxkD gene (formerly named xprF) encodes a hexokinase-like protein. We
      constructed hxkDDelta gene disruption mutants which showed increased levels of
      extracellular protease in response to carbon starvation. The hxkDDelta mutations
      are not completely recessive, indicating that the level of the gene product is
      critical. Transcript levels of hxkD increase during carbon starvation and this
      response is not dependent on functional HxkD. A gene encoding a second atypical
      hexokinase (HxkC) was identified. The hxkCDelta gene disruption mutant exhibits a
      phenotype similar, but not identical, to hxkDDelta mutants. As with hxkD,
      mutations in hxkC are suppressed by loss-of-function mutations in xprG, which
      encodes a putative transcriptional activator involved in the response to nutrient
      limitation. We show that GFP-tagged HxkD was found only in nuclei suggesting a
      regulatory role for HxkD. GFP-tagged HxkC was associated with mitochondria.
      Homologs of hxkC and hxkD are conserved in multi-cellular fungi. Genes encoding
      atypical hexokinases are present in many genome sequence databases. Thus, non
      catalytic hexokinases may be widespread.

PMID- 17226030
TI  - Feeding-induced changes of melanin-concentrating hormone (MCH)-like
      immunoreactivity in goldfish brain.
AB  - Intracerebroventricular (ICV) injection of melanin-concentrating hormone (MCH)
      influences feeding behavior in the goldfish and exerts an anorexigenic action in
      goldfish brain, unlike its orexigenic action in mammals. Despite a growing body
      of knowledge concerning MCH function in mammals, the role of MCH in appetite has
      not yet been well studied in fish. The aim of the present study was to
      investigate the involvement of endogenous MCH in the feeding behavior of the
      goldfish. We examined the distribution of MCH-like immunoreactivity (MCH-LI) in
      the goldfish brain and the effect of feeding status upon this distribution.
      Neuronal cell bodies containing MCH-LI were localized specifically to four areas
      of the hypothalamus. Nerve fibers with MCH-LI were found mainly in the
      neurohypophysis, with a few in the telencephalon, mesencephalon, and
      diencephalon. The number of neuronal cell bodies containing MCH-LI in the dorsal
      area adjoining the lateral recess of the third ventricle in the posterior and
      inferior lobes of the hypothalamus showed a significant decrease in fasted fish
      compared with that in normally fed fish, although other areas showed no evident
      differences. We also administered an antiserum against fish MCH (anti-MCH serum)
      by ICV injection and examined its immuno-neutralizing effect on food intake by
      using an automatic monitoring system. Cumulative food intake was significantly
      increased by ICV injection of the anti-MCH serum. These results indicate that MCH
      potentially functions as an anorexigenic neuropeptide in the goldfish brain, and
      that the further study of the evolutionary background of the MCH system and its
      role in appetite is warranted.

PMID- 17226032
TI  - Expanded endonasal approach: a fully endoscopic completely transnasal resection
      of a skull base arteriovenous malformation.
AB  - OBJECTIVE AND IMPORTANCE: Vascular lesions with an intraosseus nidus involving
      the skull base are uncommon and challenging [Gianoli GJ, Amedee RG Vascular
      malformation of the sphenoid sinus. Ear Nose Throat J. 70:373-375;(1991), Malik
      GM, Mahmood A, Mehta BA Dural arteriovenous malformation of the skull base with
      intraosseous vascular nidus. Report of two cases. J. Neurosurg 81:620
      623;(1994)]. We present a pediatric patient, with a life-threatening
      arteriovenous malformation (AVM) of the sphenoid sinus, clivus, and ventral skull
      base, who failed routine multimodality management of AVMs. An entirely
      transsphenoidal fully endoscopic resection was used to resect this ventral
      cranial base AVM with an intraosseus nidus located in the clivus. CLINICAL
      PRESENTATION: A 4-year-old female presented with recurrent, life-threatening
      hemorrhages from a clival and ventral skull base AVM of the entire clivus and
      ventral skull base. The patient had been temporized from the age of 2-4 years
      with multiple internal and external carotid arterial particulate and alcohol
      embolizations, including both external and internal carotid artery embolizations,
      intracranial ligation of the right internal carotid artery, and gamma knife
      irradiation. Despite these multiple interventions, the patient had persistent,
      life-threatening hemorrhages from arterial recanalization and recruitment
      requiring intubation, tracheostomy, and nasopharyngeal packing. INTERVENTION: The
      patient underwent a three-stage surgical intervention to resect the AVM. An open
      subfrontal approach, as the first procedure, provided minimal access to the
      feeding vessels and was therefore aborted. A two-stage image-guided fully
      endoscopic approach via a sublabial midface approach without external incisions
      was performed. Postoperative angiography revealed minimal residual shunting in
      the pharynx and cavernous sinus. The patient has been free of significant
      hemorrhages over the past three years. CONCLUSION: Technological advances in
      endoscopic surgery and image guidance are now allowing for purely endoscopic
      surgical treatment of previously unresectable lesions with acceptable morbidity.
      We report the successful and safe resection of a ventral cranial base AVM via a
      fully endoscopic approach. This paper reports the first AVM with a purely
      intraosseus nidus of the ventral skull base and demonstrates the ability to deal
      with complex ventral skull base lesions using a fully endoscopic transsphenoidal
      technique.

PMID- 17226033
TI  - Long-term survival in children under 3 years of age with low-grade astrocytoma.
AB  - OBJECTIVE: The purpose of this study is to analyze clinical aspects and disease
      free survival (DFS) in children less than 3 years of age diagnosed with low-grade
      astrocytoma. METHODS: In a period of 24 years (1980-2004), a total of 43 (5.4%)
      children were registered with these characteristics. Twenty-three patients had
      pilocytic astrocytoma, 18 diffused, and 2 mixed. Thirty-one (72.1%) children had
      incomplete surgical tumor resection and 12 (27.9%) had a complete tumor
      resection. Twelve (27.9%) patients had cranial radiotherapy and 17 (39.5%)
      received chemotherapy. Overall survival was recorded in 23 (53%). DFS was 50% at
      250 months of follow-up for the whole group. DFS for the supratentorial group was
      60% at 250 months, whereas, for the infratentorial, it was 22% at 120 months (p =
      0.008). CONCLUSION: The only favorable prognostic pattern was the supratentorial
      presentation. Radiotherapy and chemotherapy did not alter the outcome.

PMID- 17226031
TI  - The role of Ommaya reservoir and endoscopic third ventriculostomy in the
      management of post-hemorrhagic hydrocephalus of prematurity.
AB  - OBJECTIVE: The aim of this study is to retrospectively evaluate a series of
      consecutive patients affected by post-hemorrhagic hydrocephalus in prematurity,
      treated with an implant of an Ommaya reservoir followed by ventriculo-peritoneal
      (VP) shunt and/or endoscopic third ventriculostomy (ETV) to evaluate the safety
      and efficacy of these treatment options in the management of the condition.
      METHODS: Between 2002 and 2005, 18 consecutive premature patients affected by
      intra-ventricular haemorrhage (IVH) grades II to IV, presenting with progressive
      ventricular dilatation, were operated for implant of an intra-ventricular
      catheter connected to a sub-cutaneous Ommaya reservoir. Cerebrospinal fluid was
      intermittently aspirated percutaneously by the reservoir according with the
      clinical requirements and the echographic follow-up. The patients who presented a
      progression of the ventricular dilatation were finally operated for VP shunt
      implant or ETV according with the MRI findings. RESULTS: One patient had grade
      II, 5 had grade III, and 12 had grade IV IVH. The mean age at IVH diagnosis was
      5.2 days; the mean age at reservoir implant was 17.3 days. The Ommaya reservoir
      was punctured on an average basis of 11.4 times per patient (range 2-25), and the
      mean interval between aspirations was 2.7 days. The mean CSF volume per tap was
      20 ml. One patient died for pulmonary complications during the study period. Out
      of the 17 survivors, 3 did not develop progressive ventricular dilatation, and
      their reservoir was removed; 14 developed progressive hydrocephalus, 5 of whom
      were implanted with a VP shunt and 9 received an ETV. Amongst the five shunted
      patients, two were re-admitted for shunt malfunction and had their shunt removed
      after ETV after 6.1 and 20.5 months, respectively. Amongst the nine patients who
      received an ETV, five had to be re-operated for VP shunt implant at an average
      interval of 2.17 months (range 9-172 days) because of increasing ventricular
      dilatation. Two of them had a redo third ventriculostomy with shunt removal at 11
      and 25.1 months, respectively, after insertion. The first was reimplanted with a
      VP shunt 4 days later; the second remains shunt free. Therefore, at the end of
      the follow-up period, 10 out of 17 children affected by post-hemorrhagic
      hydrocephalus in prematurity were shunt free (59%). CONCLUSIONS: The combination
      of Ommaya reservoir, VP shunt, and the aggressive use of ETV as a primary
      treatment or as an alternative to shunt revision allowed for a significant
      reduction of shunt dependency in a traditionally shunt-dependent population.
      Further studies are warranted to optimise the algorithm of treatment in these
      patients.

PMID- 17226034
TI  - Third ventriculostomy vs ventriculoperitoneal shunt in pediatric obstructive
      hydrocephalus: results from a Swiss series and literature review.
AB  - INTRODUCTION: Few series compare endoscopic third ventriculostomies (ETV) and
      ventriculoperitoneal shunts (VPS). To avoid the complications after a shunt
      insertion, there is an increased tendency to perform a third ventriculostomy. We
      reviewed all pediatric patients operated in the French-speaking part of
      Switzerland for a newly diagnosed obstructive hydrocephalus since 1992 and
      compared the outcome of patients who benefited from ETV to the outcome of
      patients who benefited from VPS. There were 24 ETV and 31 VPS. DISCUSSION: At 5
      years of follow-up, the failure rate of ETV was 26%, as compared to 42% for the
      VPS group. This trend is also found in the pediatric series published since 1990
      (27 peer-reviewed articles analyzed). CONCLUSION: In accordance to this trend,
      although a statistical difference cannot be assessed, we believe that ETV should
      be the procedure of choice in pediatric obstructive hydrocephalus.

PMID- 17226035
TI  - Pilot study of ifosfamide/carboplatin/etoposide (ICE) for peripheral blood stem
      cell mobilization in patients with high-risk or relapsed medulloblastoma.
AB  - OBJECTIVES: The purpose of this study is to evaluate the stem cell mobilization
      capacity, anti-tumor effect, and feasibility of ifosfamide/carboplatin/etoposide
      (ICE) for transplant-eligible patients with medulloblastoma. MATERIALS AND
      METHODS: Six patients (23 months to 18 years old) with high-risk or relapsed
      medulloblastoma received one cycle of ICE, which consisted of ifosfamide at 1.8
      g/m(2) for 5 days, carboplatin 400 mg/m(2) for 2 days, and etoposide 100 mg/m(2)
      for 5 days. Stem cells were mobilized with ICE followed by granulocyte colony
      stimulating factor at 10 microg kg(-1) day(-1). RESULTS: After one cycle of ICE,
      the median number of harvested CD34+ cells per apheresis session was 11.85 x
      10(6) cells/kg (range, 0.2 to 71.2 x 10(6) cells/kg). Two patients obtained a
      complete response and three patients a partial response. All patients experienced
      severe myelosuppression, and three infectious toxicities were observed.
      CONCLUSIONS: These results suggest that ICE is optimal for mobilizing stem cells,
      effective for high-risk or relapsed medulloblastoma, and tolerable with limited
      non-hematological toxicity.

PMID- 17226036
TI  - Corridor surgery: the current paradigm for skull base surgery.
AB  - INTRODUCTION: Clival chordomas are rare tumors, especially in the pediatric
      population. In this report, we present the case of a 3-year-old boy who was found
      to have a large posterior pharyngeal, clival, and posterior fossa tumor detected
      on a CT scan after a closed head injury. DISCUSSION: Further questioning revealed
      a history of ataxia and dysphagia. Imaging confirmed severe extrinsic brain stem
      compression. The tumor was resected in multiple stages utilizing a minimally
      invasive endoscopic endonasal technique along with open transfacetal,
      transcondylar approach through the carotid-vertebral window. The child suffered
      no permanent complications as a result of our treatment and his dysphagia
      significantly improved. Although a complete resection was not feasible due to
      vascular encasement by the tumor, extensive decompression was obtained with
      minimal morbidity. CONCLUSION: We present this case to illustrate a new paradigm
      of skull base surgical approaches for large clival lesions in pediatric patients
      that allows aggressive resection with minimal morbidity.

PMID- 17226037
TI  - What is the true tethered cord syndrome?
AB  - INTRODUCTION: The tethered cord syndrome (TCS) is a stretch-induced functional
      disorder of the spinal cord with its caudal part anchored by an inelastic
      structure. DISCUSSION: This article clarifies the reversible lesions that occur
      in the cord segments above any of the inelastic abnormalities. These lesions are
      found mostly in the lumbosacral cord, occasionally in the cervical cord and
      closely correlate with clinical findings. Imaging studies alone do not allow
      accurate diagnosis of the TCS. The authors emphasize the importance of adhering
      to the physiological terms "tethered cord syndrome" and "tethered spinal cord" to
      avoid controversies derived from terms that are not based on the pathophysiology
      of TCS.

PMID- 17226039
TI  - The establishment, maintenance and productivity of a laboratory colony of
      Phlebotomus similis Perfiliew, 1963 (Diptera, Psychodidae).
AB  - Phlebotomus similis is a relatively poorly understood sand fly species. This
      paper presents the results of the first successful laboratory colonization of P.
      similis. Some bionomic factors collected on the life history, behaviour, feeding
      preferences, and characteristics of developmental biology of this species are
      described. Furthermore, the parameters of the dynamics and the life history of
      this species under laboratory conditions were quantified. These results will
      facilitate further studies necessary for understanding its potential role as a
      vector of leishmaniasis in the Mediterranean.

PMID- 17226038
TI  - Assessment of neurosurgical outcome in children prenatally diagnosed with
      myelomeningocele and development of a protocol for fetal surgery to prevent
      hydrocephalus.
AB  - INTRODUCTION: Prenatal diagnosis of myelomeningocele (MMC) has permitted a better
      planning for optimum management of the disease. More recently, it has allowed for
      a possible intrauterine repair of the spinal defect. OBJECTIVE: To describe
      neurosurgical outcome in children with myelomeningocele and follow-up at a
      referral center in Fetal Medicine. Patients were characterized for the
      development of a protocol suitable for fetal surgery, and fetuses who were
      possible candidates for intrauterine surgery were identified. MATERIALS AND
      METHODS: A retrospective descriptive analysis was performed of 98 cases of fetal
      myelomeningocele, seen at CAISM-UNICAMP, from January 1994 to December 2002,
      identifying cases with a possible indication for fetal surgery. RESULTS: Mean
      gestational age at diagnosis was 29 weeks (17-39); level of lesion was above the
      sacral region in 92.84%; association with hydrocephalus occurred in 78.57%.
      During clinical course, 82.5% of patients had neurogenic bladder and 60% had
      neural and mental deficits. Potential intrauterine repair rate was 11.57%, using
      criteria from the protocol developed in our service. CONCLUSION: Myelomeningocele
      is associated with severe and frequent sequelae. In virtually 12% of our cases,
      fetal surgery could have been offered as a therapeutic option.

PMID- 17226040
TI  - Symbiotic bacteria in oocyte and ovarian cell mitochondria of the tick Ixodes
      ricinus: biology and phylogenetic position.
AB  - Under natural conditions, eukaryote cells may contain bacteria. Arthropods such
      as ticks, insects or mites are a group particularly favoured by the obligate
      intracellular bacteria. While arthropods are vectors for some of them, other
      bacteria inhabit invertebrate host cells having entered mutualistic interactions.
      Such endosymbionts dwell usually in the host cell vacuoles or cytoplasm but have
      been also reported from tick oocyte mitochondria. The microorganisms contribute
      to mitochondria degradation, but their colonies are not eliminated from the tick
      cells affected. So far, such bacteria have been detected in three research
      centres. The Italian centre has reported on results of microscope and molecular
      analyses, while the Polish centre published molecular data. The Danish centre
      registered a 16S rRNA gene fragment in GenBank. Independent comparisons of the
      16S rRNA gene sequences, carried out in the Italian and Polish centres, confirmed
      that the nucleotide sequences of the Ixodes ricinus endosymbionts formed a single
      clade with certain non-identified tick bacterium species isolated from the tick
      Haemaphysalis wellingtoni. On the other hand, pathogenic species of the genera
      Anaplasma, Ehrlichia and Rickettsia detected in I. ricinus as well as symbionts
      of the genus Wolbachia present in Culex pipiens and Drosophila simulans have been
      placed at a different site on the phylogenetic tree.

PMID- 17226041
TI  - A S-adenosylmethionine synthetase gene from the pathogenic piscine
      hemoflagellate, Cryptobia salmositica.
AB  - We report on the identification of a Cryptobia genomic DNA gene, predict it to
      encode a S-adenosylmethionine synthetase signature 1 motif and propose to name it
      S-adenosylmethionine synthetase (MAT). The open reading frame of MAT is 1,046 bp
      with 341 deduced amino acids. The MAT gene was identified using universal genome
      walking and Southern blot analysis revealed it to be a multi-copy gene. The S
      adenosylmethionine synthetase of Cryptobia salmositica amino acid sequence is
      similar to those of other pathogenic kinetoplastids (Leishmania donovani 71%,
      Leishmania major 70%, Leishmania infantum 71%, Trypanosoma brucei 72%,
      Trypanosoma cruzi 70% and T. cruzi strain CL Brener 70%). The C. salmositica MAT
      has a conserved hexapeptide GAGDQG, which is widely found in bacteria, parasitic
      protozoans and also in humans. These suggest that MAT may have highly conserved
      functions such as regulation of gene expression and biosynthesis of a multitude
      of essential metabolites.

PMID- 17226042
TI  - Refolding of a membrane protein in a microfluidics reactor.
AB  - Membrane protein production for structural studies is often hindered by the
      formation of non-specific aggregates from which the protein has to be denatured
      and then refolded to a functional state. We developed a new approach, which uses
      microfluidics channels, to refold protein correctly in quantities sufficient for
      structural studies. Green fluorescent protein (GFP), a soluble protein, and
      bacteriorhodopsin (BR), a transmembrane protein, were used to demonstrate the
      efficiency of the process. Urea-denatured GFP refolded as the urea diffused away
      from the protein, forming in the channel a uniform fluorescent band when observed
      by confocal microscopy. Sodium dodecyl sulphate-denatured BR refolded within the
      channel on mixing with detergent-lipid mixed micelles. The refolding, monitored
      by absorbance spectroscopy, was found to be flow rate dependent. This potential
      of microfluidic reactors for screening protein-folding conditions and producing
      protein would be particularly amenable for high-throughput applications required
      in structural genomics.

PMID- 17226043
TI  - Ceftriaxone associated nephrolithiasis: a prospective study in 284 children.
AB  - Urinary tract calculi have been reported to account for between 1 in 1,000 and 1
      in 7,600 hospital admissions in children in the USA. The annual incidence of
      urolithiasis in patients older than 10 years is 109 per 100,000 of the population
      in men and 36 per 100,000 of the population in women in Minnesota. The use of
      various medications is considered to be one of the etiologic factors of
      nephrolithiasis. Ceftriaxone is a widely used third-generation cephalosporin that
      is generally considered very safe, but complications such as biliary
      pseudolithiasis, and rarely, nephrolithiasis have been reported in children.
      There is limited information about urolithiasis as a side effect of ceftriaxone.
      The aim of this study was evaluation of the incidence of nephrolithiasis
      following ceftriaxone therapy in children. This quasi-experimental before and
      after study was conducted in Mofid Children's Hospital between 2003 and 2005. All
      patients were treated with 75 mg/kg intravenous ceftriaxone. Diagnosis of
      pyelonephritis was based on standard criteria. The first renal ultrasonography
      was performed on the first or second day of admission and was repeated on the
      last day of treatment. We also evaluated complicated patients for the third time
      with renal ultrasonography 3 months after treatment. Stone-forming patients
      underwent metabolic kidney stone risk factor evaluation. We evaluated 284
      patients with pyelonephritis, 185 girls and 99 boys. The first ultrasonography
      was normal in all of our patients. On the second ultrasonography renal stones
      were reported in 4 out of 284 cases (1.4% and CI=0.96-1.83%). Underlying
      metabolic risk factors could not be identified in stone-forming patients. Follow
      up ultrasonography 3 months later was normal. The results of our study suggest
      that ceftriaxone-treated patients may be at an increased risk of kidney stone
      formation. Stones passed spontaneously in all affected patients so the use of
      this effective drug can be safely continued. Close monitoring of ceftriaxone
      treated patients with regard to kidney stone formation is recommended.

PMID- 17226044
TI  - Molecular analysis of human endometrium: short-term tibolone signaling differs
      significantly from estrogen and estrogen + progestagen signaling.
AB  - Tibolone, a tissue-selective compound with a combination of estrogenic,
      progestagenic, and androgenic properties, is used as an alternative for estrogen
      or estrogen plus progesterone hormone therapy for the treatment of symptoms
      associated with menopause and osteoporosis. The current study compares the
      endometrial gene expression profiles after short-term (21 days) treatment with
      tibolone to the profiles after treatment with estradiol-only (E(2)) and E(2) +
      medroxyprogesterone acetate (E(2) + MPA) in healthy postmenopausal women
      undergoing hysterectomy for endometrial prolapse. The impact of E(2) treatment on
      endometrial gene expression (799 genes) was much higher than the effect of
      tibolone (173 genes) or E(2) + MPA treatment (174 genes). Furthermore,
      endometrial gene expression profiles after tibolone treatment show a weak
      similarity to the profiles after E(2) treatment (overlap 72 genes) and even less
      profile similarity to E(2) + MPA treatment (overlap 17 genes). Interestingly, 95
      tibolone-specific genes were identified. Translation of profile similarity into
      biological processes and pathways showed that ER-mediated downstream processes,
      such as cell cycle and cell proliferation, are not affected by E2 + MPA, slightly
      by tibolone, but are significantly affected by E(2). In conclusion, tibolone
      treatment results in a tibolone-specific gene expression profile in the human
      endometrium, which shares only limited resemblance to E(2) and even less
      resemblance to E2 + MPA induced profiles.

PMID- 17226045
TI  - FragMatch--a program for the analysis of DNA fragment data.
AB  - FragMatch is a user-friendly Java-supported program that automates the
      identification of taxa present in mixed samples by comparing community DNA
      fragment data against a database of reference patterns for known species. The
      program has a user-friendly Windows interface and was primarily designed for the
      analysis of fragment data derived from terminal restriction fragment length
      polymorphism analysis of ectomycorrhizal fungal communities, but may be adapted
      for other applications such as microsatellite analyses. The program uses a simple
      algorithm to check for the presence of reference fragments within sample files
      that can be directly imported, and the results appear in a clear summary table
      that also details the parameters that were used for the analysis. This program is
      significantly more flexible than earlier programs designed for matching RFLP
      patterns as it allows default or user-defined parameters to be used in the
      analysis and has an unlimited database size in terms of both the number of
      reference species/individuals and the number of diagnostic fragments per database
      entry. Although the program has been developed with mycorrhizal fungi in mind, it
      can be used to analyse any DNA fragment data regardless of biological origin.
      FragMatch, along with a full description and users guide, is freely available to
      download from the Aberdeen Mycorrhiza Group web page
      (http://www.aberdeenmycorrhizas.com).

PMID- 17226046
TI  - Peritoneal lavage CEA/CA125 is a prognostic factor for gastric cancer patients.
AB  - BACKGROUND: We recently found an elevation in the pre-operative peritoneal lavage
      carcinoembryonic antigen (CEA) level to be associated with an earlier detection
      of recurrent peritoneal dissemination and a poor prognosis. METHOD: Two hundred
      and twenty-nine patients with gastric cancer were intraoperatively measured for
      tumor markers, CEA and CA125 based on peritoneal lavage using a chemiluminescent
      enzyme immunoassay. RESULTS: The patients were divided into four groups. (A) The
      peritoneal lavage CEA (-) CA125 (-) group (CEA < 0.4 ng/ml, CA125 < 200 ng/ml, n
      = 129); (B) the peritoneal lavage CEA (-) CA125 (+) group (CEA < 0.4 ng/ml, CA125
      >or= 200 ng/ml, n = 50); (C) the peritoneal lavage CEA (+) CA125 (-) group (CEA
      >or= 0.4 ng/ml, CA125 < 200 ng/ml, n = 18); and (D) the peritoneal lavage CEA (+)
      CA125 (+) group (CEA >or= 0.4 ng/ml, CA125 >or= 200 ng/ml, n = 32). The 5-year
      survival of the patients in groups C and D was 40 and 26%, respectively, which
      was lower than that of the patients in any other group (group A, B; p < 0.0001).
      Recurrent sites were both peritoneal dissemination and lymph node/liver in group
      C, while those were only peritoneal dissemination in group D. CONCLUSION: This
      combined analysis of these markers is therefore considered to be helpful method
      to accurately estimate the recurrent sites and prognosis for advanced gastric
      cancer patients.

PMID- 17226047
TI  - Continuing with letrozole offers greater benefits.
AB  - OBJECTIVE: Tamoxifen has been at the foundation of adjuvant treatment to prevent
      disease recurrence in postmenopausal women with hormone-responsive early breast
      cancer. After 5 years of adjuvant tamoxifen therapy, however, options for further
      treatment are limited. Additional tamoxifen is not indicated, as no further
      benefit in disease-free survival (DFS) has been observed. The aromatase inhibitor
      letrozole significantly improves DFS over placebo in postmenopausal women who
      have completed 4.5-6.0 years of adjuvant tamoxifen. MATERIALS AND METHODS: This
      article reviews the data supporting extended adjuvant letrozole therapy.
      CONCLUSIONS: Extended adjuvant letrozole has been shown to be particularly
      effective in patients with node-positive disease, who are at a higher risk for
      disease recurrence, improving both DFS and overall survival. Extended adjuvant
      letrozole is associated with a significant increase in self-reported
      osteoporosis, but no significant increases in fracture, endometrial malignancies,
      hypercholesterolemia, or cardiovascular events and no worsening of quality of
      life, making it suitable for long-term use. The ASCO treatment guidelines
      recommend at least 2.5 years of extended adjuvant letrozole for patients
      completing tamoxifen therapy, based upon the MA.17 trial follow-up period. A
      recent cohort analysis now suggests that extended adjuvant letrozole treatment
      for at least 48 months is associated with greater benefit. The efficacy of
      letrozole for up to 10 years following tamoxifen is also being investigated.

PMID- 17226049
TI  - Clustered carbohydrates as a target for natural killer cells: a model system.
AB  - Membrane-associated oligosaccharides are known to take part in interactions
      between natural killer (NK) cells and their targets and modulate NK cell
      activity. A model system was therefore developed using synthetic glycoconjugates
      as tools to modify the carbohydrate pattern on NK target cell surfaces. NK cells
      were then assessed for function in response to synthetic glycoconjugates, using
      both cytolysis-associated caspase 6 activation measured by flow cytometry and IFN
      gamma production. Lipophilic neoglycoconjugates were synthesized to provide their
      easy incorporation into the target cell membranes and to make carbohydrate
      residues available for cell-cell interactions. While incorporation was successful
      based on fluorescence monitoring, glycoconjugate incorporation did not evoke
      artifactual changes in surface antigen expression, and had no negative effect on
      cell viability. Glycoconjugates contained Le(x), sulfated Le(x), and Le(y)
      sharing the common structure motif trisaccharide Le(x) were revealed to enhance
      cytotoxicity mediated specifically by CD16 +CD56+NK cells. The glycoconjugate
      effects were dependent on saccharide presentation in a polymeric form. Only
      polymeric, or clustered, but not monomeric glycoconjugates resulted in alteration
      of cytotoxicity in our system, suggesting that appropriate presentation is
      critical for carbohydrate recognition and subsequent biological effects.

PMID- 17226048
TI  - Cytotoxic oxysterols induce caspase-independent myelin figure formation and
      caspase-dependent polar lipid accumulation.
AB  - Oxysterols, mainly those oxidized at the C7 position, induce a complex mode of
      cell death exhibiting some characteristics of apoptosis associated with a rapid
      induction of lipid rich multilamellar cytoplasmic structures (myelin figures)
      observed in various pathologies including atherosclerosis. The aim of this study
      was to determine the relationships between myelin figure formation, cell death,
      and lipid accumulation in various cell lines (U937, THP-1, MCF-7 [caspase-3
      deficient], A7R5) treated either with oxysterols (7-ketocholesterol [7KC], 7beta
      hydroxycholesterol, cholesterol-5alpha,6alpha-epoxide, cholesterol-5beta,6beta
      epoxide, 25-hydroxycholesterol) or cytotoxic drugs (etoposide, daunorubicin,
      tunicamycin, rapamycin). Cell death was assessed by the measurement of cellular
      permeability with propidium iodide, characterization of the morphological aspect
      of the nuclei with Hoechst 33342, and identification of myelin figures by
      transmission electron microscopy. Nile Red staining (distinguishing neutral and
      polar lipids) was used to identify lipid content by flow cytometry and spectral
      imaging microscopy. Whatever the cells considered, myelin figures were only
      observed with cytotoxic oxysterols (7KC, 7beta-hydroxycholesterol, cholesterol
      5beta, 6beta-epoxide), and their formation was not inhibited by the broad
      spectrum caspase inhibitor z-VAD-fmk. When U937 cells were treated with
      oxysterols or cytotoxic drugs, polar lipid accumulation was mainly observed with
      7KC and 7beta-hydroxycholesterol. The highest polar lipid accumulation, which was
      triggered by 7KC, was counteracted by z-VAD-fmk. These findings demonstrate that
      myelin figure formation is a caspase-independent event closely linked with the
      cytotoxicity of oxysterols, and they highlight a relationship between caspase
      activity and polar lipid accumulation.

PMID- 17226050
TI  - [Urogenital malformations associated with Wilms' tumor. Molecular genetic and
      clinical aspects].
AB  - Nephroblastoma is commonly a chance finding in a series of malformation
      syndromes. With a frequency of 4-8%, urogenital malformations are amongst the
      most common congenital anomalies in Wilms' tumor patients. For various congenital
      anomalies, there is a genetic predisposition and thus an increased risk of
      developing Wilms' tumor. The WT1 gene product (WT1 protein) usually regulates
      genes that play an important role in normal kidney development and in maintaining
      kidney function. If this gene has a functional change, then this role is no
      longer possible. The consequence is the development of nephrotic syndrome and
      possibly of a Wilms' tumor.

PMID- 17226051
TI  - Non-invasive restrained ECG recording in conscious small rodents: a new tool for
      cardiac electrical activity investigation.
AB  - In vivo electrophysiology remains a suitable method to monitor cardiac activity;
      however, surface electrocardiogram (ECG) monitoring remains complicated in the
      case of small animals. Sedation has helped to maintain the animal still; however,
      it is known that anesthetic drugs impair the regulation of the cardiac electrical
      activity. To circumvent this problem, ECG monitoring using telemetry or
      restraints has been developed. This study reports a new methodology, based on a
      restraining system without further sedation, for recording ECGs on small animal
      models. We investigated its efficacy in Syrian hamsters and in several strains of
      mice, and we compared these data to those obtained with telemetry devices. We
      show that this new system can easily be used in animals of different sizes
      ranging from adult hamsters to newborn mice. When compared to telemetry, this
      restrained ECG monitoring method shows a very good yield, as 65% of total beats
      can be used for further analysis. When recorded in the same animals, RR intervals
      distributions are identical for both techniques. In conclusion, this restrained
      ECG monitoring technique is a well-suited tool for exploring various aspects of
      cardiac electrophysiology in a wide variety of small animals including very young
      mice.

PMID- 17226054
TI  - Unusual death of a baby: a dog attack and confirmation using human and canine
      STRs.
AB  - We performed an autopsy on a 3-month-old baby boy who had only one area severe
      and extensive wound to his head and face. Three unrelated miniature dachshunds
      were in the house. After our investigation, we were able to confirm that the
      wound had in fact been caused by a dog attack, and we were able to identify the
      offending dog among the three dogs using both human and canine short tandem
      repeat obtained from samples taken from the suspected dog and from the scene of
      the attack.

PMID- 17226053
TI  - Even a stopped clock tells the right time twice a day: circadian timekeeping in
      Drosophila.
AB  - "Even a stopped clock tells the right time twice a day, and for once I'm inclined
      to believe Withnail is right. We are indeed drifting into the arena of the
      unwell... What we need is harmony. Fresh air. Stuff like that" "Bruce Robinson
      (1986, ref. 1)". Although a stopped Drosophila clock probably does not tell the
      right time even once a day, recent findings have demonstrated that accurate
      circadian time-keeping is dependent on harmony between groups of clock neurons
      within the brain. Furthermore, when harmony between the environment and the
      endogenous clock is lost, as during jet lag, we definitely feel unwell. In this
      review, we provide an overview of the current understanding of circadian rhythms
      in Drosophila, focussing on recent discoveries that demonstrate how approximately
      100 neurons within the Drosophila brain control the behaviour of the whole fly,
      and how these rhythms respond to the environment.

PMID- 17226055
TI  - Phylogenetic analysis of forensically important Lucilia flies based on cytochrome
      oxidase I sequence: a cautionary tale for forensic species determination.
AB  - Forensic scientists are increasingly using DNA to identify the species of a
      tissue sample. However, little attention has been paid to basic experimental
      design issues such as replication and the selection of taxa when designing a
      species diagnostic test. We present an example using the forensically important
      fly genus Lucilia in which an increasingly larger sample size revealed that
      species diagnosis based on the commonly used cytochrome oxidase I gene (COI) was
      less straightforward than we initially thought. This locus may still be useful
      for diagnosing Lucilia specimens, but additional knowledge other than the
      genotype will be required to reduce the list of candidate species to include only
      forms that can be distinguished by COI. We believe that these results illustrate
      the importance of study design and biological knowledge of the study species when
      proposing a DNA-based identification test for any taxonomic group.

PMID- 17226056
TI  - A Honglian CMS line of rice displays aberrant F0 of F0F1-ATPase.
AB  - Honglian (HL) is one of the three major types of cytoplasmic male sterility (CMS)
      of rice (Oryza sativa L) that has been commercially used in hybrid production. In
      previous studies, the CMS in HL is shown to be associated with a chimeric gene
      orfH79 that is cotranscribed with an extra atp6 in mitochondria. This study
      demonstrated that the intact F0F1-ATPase in HL CMS line was specifically reduced
      in both of its protein quantity and enzyme activity, whereas its F1 sector was
      not affected. It implies that the F0 sector presents a labile linkage with F1. In
      the presence of fertility restorer gene, F0F1-ATPase can be recovered.
      Furthermore, orfH79 transcripts were preferentially polyadenylated, and
      consequently degraded rapidly in florets of the restored hybrid plants,
      indicating that the atp6-orfH79 is involved in the sterile phenotype. With
      inhibition of cytochrome pathway of electron transfer chain, the biomass of the
      sterile plants grown in dark was significantly lower than that of the fertile
      lines. However, the respiration measurements showed an increase in the electron
      transferring capacity in the sterile plants, suggesting that the reduction of
      biomass in sterile line was caused by the disruption of F0F1-ATPase.

PMID- 17226052
TI  - Phototransduction in mouse rods and cones.
AB  - Phototransduction is the process by which light triggers an electrical signal in
      a photoreceptor cell. Image-forming vision in vertebrates is mediated by two
      types of photoreceptors: the rods and the cones. In this review, we provide a
      summary of the success in which the mouse has served as a vertebrate model for
      studying rod phototransduction, with respect to both the activation and
      termination steps. Cones are still not as well-understood as rods partly because
      it is difficult to work with mouse cones due to their scarcity and fragility. The
      situation may change, however.

PMID- 17226057
TI  - Expression of phytoene synthase gene (Psy) is enhanced during fruit ripening of
      Cara Cara navel orange (Citrus sinensis Osbeck).
AB  - Citrus is an important fruit crop as regards accumulation of carotenoids. In
      plant carotenoid biosynthesis, phytoene synthase gene (Psy) plays a key role in
      catalyzing the head-to-head condensation of geranylgeranyl diphosphate molecules
      to produce colorless phytoene. In the present paper, we reported the phytoene
      contents determination and characterization of Psy during fruit ripening of
      "Washington" navel orange and its red-fleshed mutant "Cara Cara". Results showed
      that phytoene was exclusively accumulated in peel and pulp of "Cara Cara".
      Although phytoene was observed accumulating with fruit ripening of "Cara Cara",
      the contents in pulp were 10 times higher than those in peel. The isolated two
      Psy cDNAs were both 1520 bp in full length, containing 436 deduced amino acid
      residues, with a different amino acid at 412th. Genomic hybridization results
      showed that one or two copies might be present in "Cara Cara" and "Washington"
      genomes. During "Cara Cara" and "Washington" fruit coloration, expression of Psy
      was observed to be up-regulated, as revealed by tissue specific profiles in the
      flavedo, albedo, segment membrane and juice sacs. However, Psy expression in
      albedo of "Cara Cara" was higher than that in "Washington", as evidenced by
      phytoene accumulation in the peel.

PMID- 17226058
TI  - Influence of IBA and aphidicolin on DNA synthesis and adventitious root
      regeneration from Malus 'Jork 9' stem discs.
AB  - Adventitious root formation in Malus 'Jork 9' stem discs was studied through
      temporarily blocking DNA synthesis by application of aphidicolin (AD). Higher
      number of roots per disc (8.4) after 21 days of cultivation were formed after a
      24-h pulse of 15 microM AD, compared to control without AD application (6.7),
      with significantly more roots (3.7) already appearing at day 7, compared to 1.5
      roots on the control. The promotive effect of AD on rooting was lower at 5
      microM, while a concentration of 30 microM was slightly inhibitory. Results show
      that DNA synthesis is effectively blocked by AD, and this blockage is overcome
      after AD withdrawal. The data indicate that AD treatment influences cell
      divisions, thereby, might synchronise root initiation. The effects of different
      treatments with and without AD were studied at the cellular level by visualising
      DNA replication through BrdU-labelling. BrdU labelling further revealed temporal
      changes in the competence of the explants to respond to applied IBA. Thus, it is
      shown that the proportion of replicating nuclei present during 28-32 h is
      significantly increased in the split IBA treatment (0-4 h and 28-32 h; treatment
      C3), compared with a single IBA application during 0-8 h (treatment C3.1).

PMID- 17226059
TI  - Classification and localization of acetabular labral tears.
AB  - OBJECTIVE: The purpose of this study was to compare the findings on hip MR
      arthrography (MRA) with the published MRA and arthroscopic classifications of hip
      labral tears and to evaluate a clock-face method for localizing hip labral tears.
      DESIGN/PATIENTS: We retrospectively reviewed 65 hip MRA studies with correlative
      hip arthroscopies. Each labrum was evaluated on MRA using the classification
      system of Czerny and an MRA modification of the Lage arthroscopic classification.
      In addition, each tear was localized on MRA by using a clock-face description
      where 6 o'clock was the transverse ligament and 3 o'clock was anterior. These MRA
      findings were then correlated with the arthroscopic findings using the clock-face
      method of localization and the Lage arthroscopic classification of labral tears.
      RESULTS: At MRA, there were 42 Czerny grade 2 and 23 grade 3 labral tears and 22
      MRA Lage type 1, 11 type 2, 22 type 3 and 10 type 4 tears. At arthroscopy, there
      were 10 Lage type 1 flap tears, 20 Lage type 2 fibrillated tears, 18 Lage type 3
      longitudinal peripheral tears and 17 Lage type 4 unstable tears. The Czerny MRA
      classification and the modified MRA Lage classification had borderline
      correlation with the arthroscopic Lage classification. Localization of the tears
      using a clock-face description was within 1 o'clock of the arthroscopic
      localization of the tears in 85% of the patients. CONCLUSIONS: The Lage
      classification, which is the only published arthroscopic classification system
      for hip labral tears, does not correlate well with the Czerny MRA or an MRA
      modification of the Lage classification. Using a clock-face description to
      localize tears provides a way to accurately localize a labral tear and define its
      extent.

PMID- 17226060
TI  - Effect of pedaling technique on muscle activity and cycling efficiency.
AB  - The purpose of this study was to examine the acute effect of talocrural joint
      position on muscle activity and gross mechanical efficiency (GE). Eleven trained
      cyclists participated in three randomized 6-min cycling bouts at approximately
      80% of maximal aerobic capacity on an electromagnetically braked cycle ergometer
      while oxygen consumption and muscle activity (EMG) were monitored during the
      subject's self-selected pedaling technique (control) and while using a dorsi- and
      plantarflexed pedaling technique. The mean differences in range of motion of the
      dorsi- and plantarflexed technique from the control position were 7.1 +/- 4.4 and
      6.9 +/- 5.4 degrees , respectively. Gastrocnemius EMG activity was higher with
      the dorsiflexion technique than when using the self-selected control position
      (33.2 +/- 13.0 and 24.2 +/- 8.4 microV s, respectively; P < 0.05). Moreover, GE
      was 2.6% lower while riding with the dorsiflexion technique than the control
      position (19.0 +/- 1.2 and 19.5 +/- 1.3%, respectively; P < 0.05). The data
      suggested that introducing more dorsiflexion into the pedal stroke of a trained
      cyclist increases muscle activity of the gastrocnemius lateralis and decreased GE
      when compared to the self-selected pedal stroke.

PMID- 17226061
TI  - Postural differences in hemodynamics and diastolic function in healthy older men.
AB  - The shift from upright to supine posture increases stroke volume in healthy young
      adults, primarily through increased end-diastolic volume. Aging is associated
      with increased ventricular stiffness and impaired diastolic function. The purpose
      of this study was to determine whether the stroke volume change between the
      upright and supine posture was blunted in healthy older men and whether the early
      mitral inflow response to this postural change was reduced by aging. Pulsed
      Doppler echocardiography and tissue Doppler imaging were used to assess stroke
      volume and left ventricular function during upright and supine posture in 10
      young and 12 older healthy men. Cardiac output was greater in the supine versus
      upright condition in both groups. In young men supine posture was associated with
      a large increment in stroke volume (63.1 +/- 7.2 upright to 98.6 +/- 11.7 ml
      supine; P < 0.05) and a decrease in heart rate. In older men, the stroke volume
      increment was smaller (63.9 +/- 3.6 upright to 82.0 +/- 5.7 ml supine; P < 0.05)
      and heart rate decreased less than young men when comparing upright to supine
      posture. Increased stroke volume was associated with higher peak early diastolic
      filling velocity (E) in young men and higher peak late diastolic filling velocity
      (A) in older men. These findings indicate that healthy aging attenuates the
      increase in early filling associated with moving from an upright to a supine
      posture. Furthermore, healthy older men are more dependent upon atrial diastolic
      filling to augment end-diastolic and stroke volume, which may be due to age
      associated increases in left ventricular filling pressure and impaired
      compliance.

PMID- 17226062
TI  - Effects of high-intensity training and acute exercise on in vitro function of rat
      sarcoplasmic reticulum.
AB  - To evaluate the effects of high-intensity training and/or a single bout of
      exercise on in vitro function of the sarcoplasmic reticulum (SR), the rats were
      subjected to 8 weeks of interval running program (final training: 2.5-min running
      x 4 sets per day, 50 m/min at 10% incline). Following training, SR function,
      i.e., Ca2+-ATPase activity and Ca2+-uptake and release rates, was examined in
      homogenates of the superficial region of the vastus lateralis muscle from rats
      subjected to a single bout of treadmill running (50 m/min at 10% incline) for 2.5
      min or to exhaustion. Training brought about a 12.4% increase (P < 0.05) in SR
      Ca2+-uptake rate in rested muscles. This change was not accompanied by
      alterations in Ca2+-ATPase activity, Ca2+-release rate, Ca2+ dependence of enzyme
      and protein contents of Ca2+-ATPase and ryanodine receptor. A single bout of high
      intensity exercise to exhaustion evoked significant reductions (P < 0.05) in SR
      function, irrespective of whether or not the animals were trained. For 2.5-min
      run and exhausted rats, no differences existed between SR functions of untrained
      and trained muscles. These data suggest that high-intensity training may be
      capable of enhancing SR Ca2+-sequestering ability, and may not protect against
      decreasing SR function with high-intensity exercise.

PMID- 17226063
TI  - A case of infant swapping by wild northern muriquis (Brachyteles hypoxanthus).
AB  - Allo-parenting has been observed in a variety of female primates, and typically
      infants are reunited with their biological mothers assuming that their mothers
      are alive. We observed an exception to this pattern when two wild northern
      muriquis (Brachyteles hypoxanthus) exchanged infants of different sexes and then
      reared their adopted infants through weaning. The process of this exchange began
      when the infants were 4 and 8 days old, respectively. The mother of a 4-day old
      female carried and nursed her own daughter and the 8-day old son of a second
      female. The exchange ended when the second mother was first observed carrying the
      wrong infant 1.5 days later. This observation raises questions about the age and
      mechanisms of mother-infant recognition in this species, and about assumptions of
      mother-infant relatedness based on behavioral observations alone.

PMID- 17226064
TI  - Do age- and sex-related variations reliably reflect body size in non-human
      primate vocalizations? A review.
AB  - In vocal communication, the mechanisms of sound production are well understood.
      The length of the vocal folds determines the minimum fundamental frequency, while
      the size and the shape of the vocal tract affect its filtering characteristics
      and hence, the resonant frequencies. Both measures-vocal fold length and vocal
      tract length-are related to body size and therefore, acoustic features are
      expected to vary with body size. Because direct measures of body size are
      difficult to obtain from free-ranging animals, age and sex have often been used
      as proxies. We surveyed studies which included direct measures of size or weight,
      and also studies in which only age and/or sex differences were examined. The main
      purpose was to examine whether age- and sex-related variations in acoustic
      features meet the predictions generated from our knowledge about sound
      production. Our survey revealed that compared to smaller animals, larger animals
      utter longer calls, with a lower fundamental frequency, with smaller formant
      dispersion, and with the energy concentrated in lower frequencies. Age and sex
      reliably reflect the influence of body size on acoustic features when gross size
      differences are examined. However, within age- and sex classes, this relationship
      may break down. In addition to body size, other factors such as internal state or
      social context may also influence the structure of vocal signals and highlight
      the richness of information in calls that is potentially available to listeners.

PMID- 17226065
TI  - Hepatotoxicity induced by alendronate therapy.
AB  - Here we describe a 47-year-old postmenopausal woman who had been taking
      alendronate 70 mg/week for osteoporosis. After two months of alendronate therapy,
      she developed hepatotoxicity, and no other etiological factors for this besides
      the alendronate were apparent. After the alendronate therapy was discontinued,
      the patient's hepatic enzyme levels slowly returned to normal. Hepatotoxicity due
      to alendronate therapy is a rare but possible adverse effect.

PMID- 17226066
TI  - Identification and characterisation of tomato torrado virus, a new plant picorna
      like virus from tomato.
AB  - A new virus was isolated from tomato plants from the Murcia region in Spain which
      showed symptoms of 'torrado disease'; very distinct necrotic, almost burn-like
      symptoms on leaves of infected plants. The virus particles are isometric with a
      diameter of approximately 28 nm. The viral genome consists of two (+)ssRNA
      molecules of 7793 (RNA1) and 5389 nts (RNA2). RNA1 contains one open reading
      frame (ORF) encoding a predicted polyprotein of 241 kDa that shows conserved
      regions with motifs typical for a protease-cofactor, a helicase, a protease and
      an RNA-dependent RNA polymerase. RNA2 contains two, partially overlapping ORFs
      potentially encoding proteins of 20 and 134 kDa. These viral RNAs are
      encapsidated by three proteins with estimated sizes of 35, 26 and 23 kDa. Direct
      protein sequencing mapped these coat proteins to ORF2 on RNA2. Phylogenetic
      analyses of nucleotide and derived amino acid sequences showed that the virus is
      related to but distinct from viruses belonging to the genera Sequivirus,
      Sadwavirus and Cheravirus. This new virus, for which the name tomato torrado
      virus is proposed, most likely represents a member of a new plant virus genus.

PMID- 17226067
TI  - Application of Phi29 DNA polymerase in identification and full-length clone
      inoculation of tomato yellow leaf curl Thailand virus and tobacco leaf curl
      Thailand virus.
AB  - Tomato plants grown in greenhouses in Thailand developed typical symptoms of a
      tomato yellow leaf curl Thailand virus (TYLCTHV) infection. After confirmation by
      ELISA, a Phi29 DNA polymerase approach was chosen for further molecular analysis
      of TYLCTHV. Total DNA purified from infected tomato leaves was subjected to
      rolling-circle amplification (RCA) of DNA-A and DNA-B of TYLCVTHV. In addition, a
      new monopartite geminivirus with a putative recombinant background was identified
      by RCA and tentatively named tobacco leaf curl Thailand virus (TbLCTHV). To
      confirm the composition of both geminiviruses, full-length clones were
      established and used for inoculation of Nicotiana benthamiana by particle
      bombardment or agroinfection. When TYLCTHV DNA-A and DNA-B were applied together
      by particle bombardment or agroinfection, severe stunting, yellowing, and leaf
      curling were observed. Whereas TYLCTHV DNA-A and TbLCTHV revealed no infection
      after'particle bombardment, similar symptoms in N. benthamiana, like leaf upward
      curling and yellowing were observed following agroinfection.DNA components of
      TYLCTHV DNA-A and DNA-B were excised from their respective plasmids, ligated, and
      amplified by Phi29 DNA polymerase. The ability of viral concatamere inoculation
      was evaluated in particle co-bombardment experiments on N. benthamiana. Thus,
      particle bombardment of RCA-derived multimeric products proved to be at least as
      effective as inoculation with a partial repeat construct and tenfold as effective
      as inoculation with excised unit-lengths of DNA-A and DNA-B of TYLCVTHV when
      using each DNA component in an amount of 5 ng.

PMID- 17226068
TI  - Molecular characterization of infectious bursal disease virus (IBDV): diversity
      of very virulent IBDV in Tanzania.
AB  - Nucleotide sequences of the VP2 hypervariable region (VP2-HVR) of 14 infectious
      bursal disease viruses (IBDVs) isolated in Tanzania from 2001 to 2004 were
      determined. Phylogenetic analysis showed that the isolates diverged into two
      genotypes and belonged to the very virulent (VV) type. In the phylogenetic tree,
      strains in one genotype clustered in a distinct group and were closely related to
      some strains isolated in western Africa, with nucleotide similarities of 96.1
      96.8%, while strains in another genotype were clustered within the European/Asian
      VV type with nucleotide similarities ranging from 97.5 to 99.3%. Both genotypes
      were widely distributed throughout Tanzania, and had conserved putative virulence
      marker amino acids (aa) at positions 222(A), 242(I), 256(I), 294(I) and 299(S).
      Our findings demonstrate for the first time the existence of both African and
      European/Asian VV-IBDV variants in Tanzania.

PMID- 17226069
TI  - Changes in glycoprotein components in streptozotocin--nicotinamide induced type 2
      diabetes: influence of tetrahydrocurcumin from Curcuma longa.
AB  - Curcuma longa (Zingiberaceae) has been used traditionally as antidiabetic, and
      has been proven scientifically to possess high antioxidant activity and
      anticancer properties. The active components of Curcuma longa such as curcumin
      and tetrahydrocurcumin (THC), a major colourless metabolite of curcumin also
      possesses antidiabetic, antiinflammatory and antioxidant activity. The
      ethnopharmacological value of this plant, the effect of THC on glycoproteins was
      carried out in normal and streptozotocin-nicotiniamide induced type 2
      hyperglycaemic rats for 45 days. Glucose, plasma insulin and glycoprotein
      components in plasma and tissues (hexose, hexosamine, fucose and sialic acid)
      were determined. Oral administration of THC to diabetic rats showed a decrease in
      the level of blood glucose and plasma glycoproteins. The levels of plasma insulin
      and tissue sialic acid were increased where as the levels of tissue hexose,
      hexosamine and fucose were near normal in diabetic rats treated with THC. The
      present study indicates that the THC possesses a significant beneficial effect on
      glycoprotein moiety in addition to its antidiabetic effect. The effect of THC is
      more prominent than curcumin.

PMID- 17226070
TI  - Antihyperglycemic effects of Platycodon grandiflorum (Jacq.) A. DC. extract on
      streptozotocin-induced diabetic mice.
AB  - The root of Platycodon grandiflorum (Jacq.) A. DC has been reported to have a
      wide range of health benefits in oriental food. This study examined the
      hypoglycemic effects of Platycodon grandiflorum (Jacq.) A. DC aqueous-ethanol
      extract (PGE) in streptozotocin (STZ) -induced diabetic ICR mice (STZ diabetic
      mice) for the first time. The effects of PGE on blood glucose, plasma insulin
      levels and body weight were investigated. A significant decrease in blood glucose
      levels was observed after single administration of PGE. Furthermore,
      Glibenclamide and PGE significantly suppressed the rise in blood glucose after 30
      min in the acute glucose tolerance test. Treatment with glibenclamide and PGE
      resulted in a reduction in blood glucose levels from the 2nd week, and this
      reduction was maintained until the 4th week of treatment. The body weight changed
      slightly in glibenclamide and PGE treated mice in comparison with the STZ control
      group. Plasma insulin levels were increased with glibenclamide treatment in STZ
      diabetic mice, whereas such effect was not observed with PGE. These results
      indicated that PGE could induce hypoglycemic effects without stimulating insulin
      secretion.

PMID- 17226071
TI  - Effect of different cyclooxygenase inhibitors on gastric adaptive cytoprotection
      induced by 20% ethanol.
AB  - In this study, we evaluated the effect of two different dosages of
      therapeutically prescribed nonsteroidal anti-inflammatory drugs (NSAIDs),
      ibuprofen, diclofenac, nimesulide, meloxicam, and celecoxib (ED80 for COX-1 and
      COX-2) on normal gastric mucosa and mucosa, previously exposed to 20% ethanol. At
      COX-2-inhibiting dosages, the NSAIDs tested were nonulcerogenic, and the same
      response profile was observed in "adapted" stomachs. Interestingly, low doses of
      nimesulide and celecoxib increase the levels of Prostaglandin E(2) and COX-2, and
      protect against subsequent 100% ethanol exposition, suggesting that these drugs
      may act as "mild irritants" to gastric mucosa. The ulcerogenic response to NSAIDs
      was prevented by the previous 20% ethanol exposition, probably the result of
      nitric oxide synthesis, because PGE(2) levels in gastric mucosa were reduced by
      these agents and a concomitant nitric oxide blockade reversed this protection.

PMID- 17226072
TI  - Clinical implications of hepatic steatosis in patients with chronic hepatitis C:
      a multicenter study of U.S. veterans.
AB  - Studies have indicated a high prevalence of hepatic steatosis in patients with
      chronic hepatitis C (CHC). To address the impact of steatosis on the clinical
      course of CHC and treatment response requires large multicenter studies. The
      present study analyzed hepatitis C virus (HCV)-infected veterans enrolled in a
      U.S. Veteran Administration multicenter study of the epidemiology and response to
      interferon alpha-2b and ribavirin treatment. Of the 357 patients, 97.1% were
      males, with a mean age of 48.7+/-6.4 years, and 184 (51.5%) had hepatic
      steatosis. The mean body mass index (BMI) was 29.3+/-5.2 kg/m(2), including 37.1%
      who were obese (BMI, > or =30 kg/m(2)). Stage III-IV fibrosis was present in 111
      of 334 (33.3%) of the patients. After adjusting for age, race, and history of
      alcohol use in the past 12 months, only stage III-IV fibrosis was independently
      and significantly associated with hepatic steatosis (P=0.03). There was a trend
      of association between obesity and steatosis independent of the other factors.
      Only HCV genotype was independently associated with a sustained virological
      response (SVR) to interferon alpha-2b and ribavirin treatment after adjusting for
      age, alcohol use, steatosis, BMI, stage III-IV fibrosis, serum AFP, and HCV load.
      In conclusion, analyses of our multicenter trial data demonstrated that the
      prevalence of hepatic steatosis is 51.5% in HCV-infected U.S. veterans. We found
      that steatosis is independently associated with stage III-IV fibrosis. However,
      only HCV genotype, and not steatosis, obesity, or stage III-IV fibrosis, was
      associated with SVR to interferon alpha-2b and ribavirin treatment.

PMID- 17226073
TI  - Preconditioning stress prevents cold restraint stress-induced gastric lesions in
      rats: roles of COX-1, COX-2, and PLA2.
AB  - We investigated the protective effect of mild stress on gastric lesions induced
      by cold-restraint stress, especially concerning prostaglandins (PGs)/cyclo
      oxygenase (COX) isozymes. Rats were exposed to severe stress (cold-restraint
      stress at 10 degrees C for 6 hr) or mild stress (cold-restraint stress at 10
      degrees C for 30 min and kept at room temperature for 60 min) followed by severe
      stress. Severe stress induced gastric lesions, with a concomitant decrease in
      body temperature (BT). The ulcerogenic response was inhibited by atropine but
      worsened by indomethacin and SC-560 but not rofecoxib, although none of these
      agents had any effect on the change in BT. Mild stress suppressed the gastric
      ulceration and the decrease in BT induced by severe stress, and these effects
      were reversed by both COX-1 and COX-2 inhibitors. The expression of COX-2 in the
      stomach was up-regulated from 4 hr after severe stress and this response was
      slightly expedited by mild stress. COX-2 was also expressed in the hypothalamus
      under normal and stressed conditions. Quinacrine (phospholipase A(2) inhibitor)
      attenuated the protective effect of mild stress on the ulceration and decrease in
      BT caused by severe stress. TA-0910 (TRH analogue) at a low dose also prevented
      the gastric ulceration and the decrease in BT induced by severe stress. These
      results suggest that mild stress protects against cold-restraint stress-induced
      gastric ulceration, and the effect is peripherally and centrally mediated by PGs
      derived from both COX-1 and COX-2 through the activation of phospholipase A(2).
      TRH may also be involved in the protective effect of mild stress, probably
      through regulation of the thermogenic system.

PMID- 17226074
TI  - Remission of primary duodenal adenocarcinoma with liver metastases with S-1
      chemotherapy.

PMID- 17226076
TI  - Intrahepatic plastic stent entrapment due to guide wire stripping.

PMID- 17226075
TI  - Altered expression of a Li-cadherin in gastric cancer and intestinal metaplasia.
AB  - The aims of this study were to examine Li-cadherin expression in 74 gastric
      carcinoma tissues, 10 cases with normal gastric tissues, and 21 cases with
      intestinal metaplasia and to investigate the role of Li-cadherin in cell
      differentiation, cancer invasion, and metastasis. Expression of Li-cadherin was
      analyzed by immunohistochemistry and semiquantitative polymerase chain reaction
      and correlated with clinicopathological parameters. Immunohistochemistry showed
      that Li-cadherin was mainly present on the cell membrane and there was no
      staining for liver-intestine cadherin in normal tissues. The reduction of Li
      cadherin mRNA expression was inversely correlated with the grade of
      differentiation (P < 0.05). Significant differences in the expression of liver
      intestine cadherin were found in lymphatic metastasis of the tumors (P < 0.05),
      but the expression of liver-intestine cadherin was not associated with gender
      (P=0.748), serosal invasion (P=0.136), TNM stage (P=0.172), Helicobacter pylori
      infection (P=0.572), liver metastasis (P=0.374), or peritoneal metastasis
      (P=0.621). Multivariate analysis revealed that the expression of Li-cadherin is
      an important predictor of lymph node metastasis. We conclude that there is a
      significant correlation between Li-cadherin expression and the differentiation of
      gastric carcinoma, and Li-cadherin can be a good marker to detect gastric cancer
      at early stages. Increased Li-cadherin expression may contribute to gastric
      cancer invasion to lymph nodes.

PMID- 17226077
TI  - Intrauterine insemination in natural cycle may give better results in older
      women.
AB  - BACKGROUND: Controlled ovarian hyper-stimulation (COH) in combination with
      intrauterine insemination (IUI) has been shown to result in significantly higher
      pregnancy rates compared to un-stimulated (natural cycle) IUI. This may however
      not be true in all ages. METHODS: We performed a retrospective cohort study and
      analysed data collected prospectively on 1759 IUI cycles in couples with
      unexplained infertility. The results were analysed to show the outcome of IUI
      with COH, and IUI in natural cycle (unstimulated), in younger women compared to
      their older counterparts. RESULTS: In women age 37 and younger, COH resulted in a
      significantly higher pregnancy rate (13.0% vs 6.5%) and live-birth rate (10.7% vs
      5.2%) compared to natural cycle IUI (p = 0.025, p = 0.045 respectively). However
      for older women age >37 years, natural cycle (unstimulated) IUI, resulted in a
      significantly higher pregnancy rate (12.0% vs 8.5%) live-birth rate (7.5%vs 3.5%)
      than IUI with COH ((p = 0.0037). This difference is even more significant when
      COH was performed with clomiphene citrate (7.5% vs 2.1%) (p = 0.0017).
      CONCLUSION: COH was associated with a lower live birth rate in older women,
      irrespective of the agent used, and it seems to be worse when the anti
      oestrogenic drug clomiphene citrate was used for COH. Older women may benefit
      more from natural cycle (unstimulated) IUI. A randomised controlled trial is
      required to confirm this observation.

PMID- 17226078
TI  - Molecular cloning, mapping, and expression analysis of the EIF4A2 gene in pig.
AB  - A full-length cDNA clone encoding the eukaryotic translation initiation factor
      4A, isoform 2 (EIF4A2), was cloned from the fetal skeletal cDNA library from the
      pig (Sus scrofa). EIF4A2 is a highly conserved gene for one of the protein
      synthesis initiation factors involved in the binding of mRNA to the ribosome.
      Based on this cDNA sequence, the deduced protein of 407 amino acids contains the
      characteristic motifs shared by the DEAD-box supergene family. The genomic
      nucleotide sequence of this gene was determined and a single nucleotide
      polymorphism located in the 5' untranslated region was genotyped. The porcine
      EIF4A2 was expressed in all tissues examined but in variable amounts. The EIF4A2
      expression level in muscle was upregulated through embryonic and neonatal
      development until adult, suggesting that porcine EIF4A2 was possibly involved in
      translation regulation of other muscle-related genes in muscle formation and
      development. In addition, we mapped porcine EIF4A2 to q4.1 of SSC13, in agreement
      with comparative mapping data.

PMID- 17226079
TI  - Patterns of genetic variation in Swertia przewalskii, an endangered endemic
      species of the Qinghai-Tibet Plateau.
AB  - Swertia przewalskii Pissjauk. (Gentianaceae) is a critically endangered and
      endemic plant of the Qinghai-Tibet Plateau in China. RAPD and ISSR analyses were
      carried out on a total of 63 individuals to assess the extent of genetic
      variation in the remaining three populations. Percentage of polymorphic bands was
      94% (156 bands) for RAPD and 96% (222 bands) for ISSR. A pairwise distance
      measure calculated from the RAPD and ISSR data was used as input for analysis of
      molecular variance (AMOVA). AMOVA indicated that a high proportion of the total
      genetic variation (52% for RAPD and 56% for ISSR) was found among populations;
      pairwise Phi (ST) comparisons showed that the three populations examined were
      significantly different (p < 0.001). Significant genetic differentiation was
      found based on different measures (AMOVA and Hickory theta(B)) in S. przewalskii
      (0.52 on RAPD and 0.56 on ISSR; 0.46 on RAPD and 0.45 on ISSR). The
      differentiation of the populations corresponded to low average gene flow (0.28
      based on RAPD and 0.31 based on ISSR), whereas genetic distance-based clustering
      and coalescent-based assignment analyses revealed significant genetic isolation
      among populations. Our results indicate that genetic diversity is independent of
      population size. We conclude that although sexual reproduction and gene flow
      between populations of S. przewalskii are very limited, they have preserved high
      levels of genetic diversity. The main factors responsible for the high level of
      difference among populations are the isolation and recent fragmentation under
      human disturbance.

PMID- 17226080
TI  - Associations between residential segregation and smoking during pregnancy among
      urban African-American women.
AB  - Approximately 10% of African-American women smoke during pregnancy compared to
      16% of White women. While relatively low, the prevalence of smoking during
      pregnancy among African-American women exceeds the Healthy People 2010 goal of
      1%. In the current study, we address gaps in extant research by focusing on
      associations between racial/ethnic residential segregation and smoking during
      pregnancy among urban African-American women. We linked measures of segregation
      to birth certificates and data from the 2000 census in a sample of US-born
      African-American women (n = 403,842) living in 216 large US Metropolitan
      Statistical Areas (MSAs). Logistic regression models with standard errors
      adjusted for multiple individual observations within MSAs were used to examine
      associations between segregation and smoking during pregnancy and to control for
      important socio-demographic confounders. In all models, a u-shaped relationship
      was observed. Both low segregation and high segregation were associated with
      higher odds of smoking during pregnancy when compared to moderate segregation. We
      speculate that low segregation reflects a contagion process, whereby salutary
      minority group norms are weakened by exposure to the more harmful behavioral
      norms of the majority population. High segregation may reflect structural
      attributes associated with smoking such as less stringent tobacco control
      policies, exposure to urban stressors, targeted marketing of tobacco products, or
      limited access to treatment for tobacco dependence. A better understanding of
      both deleterious and protective contextual influences on smoking during pregnancy
      could help to inform interventions designed to meet Healthy People 2010 target
      goals.

PMID- 17226081
TI  - Symptoms of posttraumatic stress disorder in a New Orleans workforce following
      Hurricane Katrina.
AB  - On August 29, 2005, Hurricane Katrina made landfall resulting in catastrophic
      damage and flooding to New Orleans, LA, and the Gulf Coast, which may have had
      significant mental health effects on the population. To determine rates and
      predictors of symptoms consistent with a diagnosis of posttraumatic stress
      disorder (PTSD) in New Orleans residents following Hurricane Katrina, we
      conducted a web-based survey 6 months after Hurricane Katrina made landfall.
      Participants included 1,542 employees from the largest employer in New Orleans.
      The prevalence of PTSD symptoms was 19.2%. Predictors of PTSD symptoms in a
      multivariate-adjusted regression model included female sex, non-black race,
      knowing someone who died in the storm, not having property insurance, having had
      a longer evacuation, a much longer work commute compared to before Hurricane
      Katrina, and currently living in a newly purchased or rented house or in a
      temporary trailer. Despite universal health coverage and the benefits of an
      employee assistance program for all employees, only 28.5% of those with PTSD
      symptoms had talked to a health professional about the events of Hurricane
      Katrina or issues encountered since the storm. A significant burden of PTSD
      symptoms was present 6 months following Hurricane Katrina among a large group of
      adults who had returned to work in New Orleans. Given their key role in the
      economic redevelopment of the region, there is a tremendous need to identify
      those in the workforce with symptoms consistent with PTSD and to enhance
      treatment options. The strong relationship between displacement from one's pre
      Katrina residence and symptoms of PTSD suggests a need to focus resource
      utilization and interventions on individuals living in temporary housing.

PMID- 17226083
TI  - Comparison of performance characteristics between new and reprocessed
      electrophysiology catheters.
AB  - OBJECTIVE: Electrophysiology (EP) catheter reprocessing is widespread and
      previous studies have examined clinical performance, sterility and safety of
      these reprocessed devices. Here we compare the intrinsic engineering
      characteristics, electrical, mechanical and safety, between new and reprocessed
      devices. MATERIALS AND METHODS: New (58 devices) and clinically used (five
      times)/reprocessed (165 devices) EP catheters from five manufacturers were
      employed to examine and compare catheter electrode continuity, electrode
      isolation, electrical leakage current, shaft torsion and stiffness
      characteristics as well as tip buckling and bond strengths. RESULTS: Electrode
      continuity, isolation and leakage currents for both new and reprocessed EP
      catheters were within acceptance criteria for electrode continuity (<30 Omega)
      and shaft electrical leakage (<0.5 mA) as well as electrode isolation (>200
      Omega). In addition, reprocessed catheters were equivalent when compared with
      their new counterparts. While catheter shaft torque forces varied five fold
      amongst manufacturers, comparison between new and reprocessed devices within a
      manufacturer showed no significant differences. Likewise shaft stiffness showed
      no significant difference between new and reprocessed devices. Average tip
      buckling forces for all catheters were substantially below the acceptance
      criteria of 0.45 lb (between 0.04 and 0.1 lb) with differences between new and
      reprocessed catheters not being significant. All bond strengths for both new and
      reprocessed catheters exceeded the acceptance criteria specified in ISO 10555-1.
      CONCLUSIONS: This study found that reprocessed EP catheters which had undergone
      five actual clinical use/reprocessing cycles met and exceeded acceptance criteria
      specified by industry standards as well as individual manufacturer's criteria for
      both electrical and safety characteristics. We conclude that reprocessed EP
      catheters exhibit electrical, mechanical and safety characteristics which are
      equivalent to their new counterparts.

PMID- 17226082
TI  - Pulmonary vein encircling ablation alters the atrial electrophysiologic response
      to autonomic stimulation.
AB  - OBJECTIVE: Pulmonary vein encircling ablation is often effective in the treatment
      of atrial fibrillation (AF). The success of the procedure does not depend upon
      creation of continuous lines of block. Thus mechanisms by which pulmonary vein
      encircling can cure AF remain unclear. Stimulation of cardiac autonomic ganglia
      alters atrial refractoriness and potentiates AF. We hypothesized that pulmonary
      vein encircling alters atrial autonomic function and that these alterations
      account in part for prevention of AF recurrences following ablation. METHODS:
      Atrial effective refractory periods (ERP) and AF inducibility were quantified in
      ten dogs before and during central autonomic nerve stimulation. Pulmonary vein
      encircling ablation was then performed and electrophysiologic testing repeated.
      In two dogs subjected to sham procedures measurements were repeated without
      performance of ablation. Hearts were examined histologically. RESULTS: Autonomic
      nerve stimulation led to decreased atrial refractoriness and increased AF
      inducibility and duration. Each of these effects were attenuated following
      pulmonary vein encircling (e.g., mean ERP decreased before (-23.7 +/- 1.8, p <
      0.001) but not after ablation (-2.3 +/- 1.9, p = 0.25); AF inducibility increased
      by 26% before vs. 5% after ablation). No attenuation was seen in the sham
      operated animals. Histologic analysis following pulmonary vein encircling
      demonstrated destruction of some but not all autonomic ganglia. CONCLUSION:
      Autonomic stimulation shortens atrial refractory periods and potentiates AF.
      Pulmonary vein encircling ablation partially destroys atrial autonomic inputs,
      attenuates the refractory period shortening effect of autonomic stimulation and
      decreases AF inducibility. Destruction of autonomic ganglia may contribute to the
      anti-fibrillatory effects of pulmonary vein encircling and warrants further
      investigation.

PMID- 17226084
TI  - Variation in left atrial transmural wall thickness at sites commonly targeted for
      ablation of atrial fibrillation.
AB  - BACKGROUND: The number of catheter ablations performed for atrial fibrillation
      (AF) has increased dramatically over the past several years. Regional variation
      in left atrial (LA) wall thickness is known to exist but have not been described
      in detail. AF ablation success and complication rates may be related to regional
      differences in LA wall thickness. OBJECTIVE: To evaluate differences in
      transmural wall thickness in five pre-defined anatomic areas within the LA which
      are commonly targeted for AF ablation. MATERIALS AND METHODS: We measured LA wall
      transmural thickness in 34 human heart specimens using calipers in five anatomic
      areas frequently targeted during AF ablation (anterior wall, septum, mitral
      isthmus, posterior wall and roof). RESULTS: The autopsied individuals were 53%
      female, 67.7% had CAD, 14.7% had atrial fibrillation, 61.8% had hypertension, and
      21.6% had congestive heart failure. The roof was the thinnest region with mean
      thickness measuring significantly less than each other area (p 0.005 for the
      posterior wall and <0.001 for all other areas). The septum was the thickest
      region with mean thickness measuring significantly greater than each other area
      (p = 0.05, 0.001, <0.001, <0.001 measured against the anterior wall, isthmus,
      posterior wall and roof, respectively). CONCLUSIONS: Significant regional
      differences exist for mean left atrial wall thickness among the different
      anatomic areas within the left atrium which are often targeted during catheter
      ablation of AF. These differences may have significant implications in
      determining the ideal intensity and total duration of radiofrequency energy
      required to achieve a safe and successful ablation.

PMID- 17226085
TI  - Transient left ventricular apical ballooning following a prolonged ablation.
AB  - The authors report a case of transient left ventricular apical ballooning after a
      prolonged electrophysiology procedure. Interventional electrophysiologists should
      be aware of this syndrome as a potential complication.

PMID- 17226086
TI  - Transvenous dual site left ventricular pacing plus biventricular pacing for the
      management of refractory ventricular tachycardia.
AB  - This is a case report of a male patient with nonischemic cardiomyopathy who had
      severely depressed left ventricular systolic function and functional class III
      congestive heart failure (CHF). He also had left bundle branch block (LBBB) and
      recurrent ventricular tachycardia (VT). Though the patient's CFH functional class
      improved after implantation of a transvenous biventricular ICD system, recurrent
      VT episodes required the initiation of amiodarone. After an improved condition
      for 28 months, recurrent VT episodes led to multiple consecutive ICD shocks,
      which constituted an electrical storm and a battery status of elective
      replacement indicator (ERI). The recurrent VT episodes were suppressed with
      intravenous amiodarone and lidocaine. As Radiofrequency ablation was declined by
      the patient, a new left ventricular (LV) lead was transvenously added, providing
      biventricular and dual site LV pacing. After this intervention the arrhythmia
      subsided and the intravenous antiarrhythmic medications were stopped. No episodes
      of sustained VT leading to ICD shocks were observed for the following 9 months.
      The events in this case suggest that dual site LV pacing with biventricular
      pacing could be an alternative strategy for the management of refractory VT.

PMID- 17226087
TI  - Does the rate of inappropriate therapy differ in implantable cardioverter
      defibrillators from different manufacturers?
AB  - OBJECTIVE: We conducted this study to compare the rate of >/=1 inappropriate
      therapy between ICDs from two manufacturers which use different discriminatory
      protocols. METHOD: One hundred sixty two patients (mean age 58 +/- 13 years, 126
      male) who received ICDs between January 2001 and 2005 were included in the study.
      Clinical, electrocardiographic, and ICD stored data and electrograms were
      collected and analyzed. Immediately after implantation all the detection and
      discrimination criteria were activated with the nominal values in order to
      compare the two discriminatory protocols under the default manufacturer's
      settings. RESULTS: During the follow up period of 14.3 +/- 10 months, 49 (30%)
      patients received >/=1 inappropriate ICD therapy. The rate of >/=1 inappropriate
      ICD therapy in manufacturer A and B ICDs was 26% (n = 29) and 41% (n = 20),
      respectively. Comparing the rate of >/=1 inappropriate ICD therapy between the
      two groups by Kaplan-Meier analysis and the log rank test resulted in P = 0.04.
      CONCLUSION: Having all discriminatory variables activated with the nominal
      values, discriminatory performance differs between the two manufacturers. Further
      larger-scale studies are warranted to prospectively compare the performance of
      various available ICDs' discriminatory protocols, and define the optimum
      combination of discriminators in each ICD to decrease the rate of inappropriate
      therapy.

PMID- 17226088
TI  - Local cortical circuit model inferred from power-law distributed neuronal
      avalanches.
AB  - How cortical neurons process information crucially depends on how their local
      circuits are organized. Spontaneous synchronous neuronal activity propagating
      through neocortical slices displays highly diverse, yet repeatable, activity
      patterns called "neuronal avalanches". They obey power-law distributions of the
      event sizes and lifetimes, presumably reflecting the structure of local circuits
      developed in slice cultures. However, the explicit network structure underlying
      the power-law statistics remains unclear. Here, we present a neuronal network
      model of pyramidal and inhibitory neurons that enables stable propagation of
      avalanche-like spiking activity. We demonstrate a neuronal wiring rule that
      governs the formation of mutually overlapping cell assemblies during the
      development of this network. The resultant network comprises a mixture of
      feedforward chains and recurrent circuits, in which neuronal avalanches are
      stable if the former structure is predominant. Interestingly, the recurrent
      synaptic connections formed by this wiring rule limit the number of cell
      assemblies embeddable in a neuron pool of given size. We investigate how the
      resultant power laws depend on the details of the cell-assembly formation as well
      as on the inhibitory feedback. Our model suggests that local cortical circuits
      may have a more complex topological design than has previously been thought.

PMID- 17226089
TI  - Identification of human term and preterm labor using artificial neural networks
      on uterine electromyography data.
AB  - OBJECTIVE: To use artificial neural networks (ANNs) on uterine electromyography
      (EMG) data to classify term/preterm labor/non-labor pregnant patients. MATERIALS
      AND METHODS: A total of 134 term and 51 preterm women (all ultimately delivered
      spontaneously) were included. Uterine EMG was measured trans-abdominally using
      surface electrodes. "Bursts" of elevated uterine EMG, corresponding to uterine
      contractions, were quantified by finding the means and/or standard deviations of
      the power spectrum (PS) peak frequency, burst duration, number of bursts per unit
      time, and total burst activity. Measurement-to-delivery (MTD) time was noted for
      each patient. Term and preterm patient groups were sub-divided, resulting in the
      following categories: [term-laboring (TL): n = 75; preterm-laboring (PTL): n =
      13] and [term-non-laboring (TN): n = 59; preterm-non-laboring (PTN): n = 38],
      with labor assessed using clinical determinations. ANN was then used on the
      calculated uterine EMG data to algorithmically and objectively classify patients
      into labor and non-labor. The percent of correctly categorized patients was
      found. Comparison between ANN-sorted groups was then performed using Student's t
      test (with p < 0.05 significant). RESULTS: In total, 59/75 (79%) of TL patients,
      12/13 (92%) of PTL patients, 51/59 (86%) of TN patients, and 27/38 (71%) of PTN
      patients were correctly classified. CONCLUSION: ANNs, used with uterine EMG data,
      can effectively classify term/preterm labor/non-labor patients.

PMID- 17226090
TI  - Identification of youth psychosocial problems during pediatric primary care
      visits.
AB  - This investigation applied the Gateway Provider Model (GPM) of child mental
      health services to investigate whether characteristics of the child, family,
      visit, and provider were related to the identification of youth psychosocial
      problems during primary care visits. Data were gathered during 774 visits to 54
      primary care providers (PCPs) at 13 clinics. Similar to previous investigations
      in primary care settings, 42% of youth demonstrated at least a sub-threshold
      clinical mental health problem. Most PCPs reported high job satisfaction and
      control, but reported varying access to mental health specialists. PCPs generally
      had positive attitudes and beliefs about treating psychosocial problems but many
      reported that doing so was burdensome. Identification was more likely when the
      visit was for a mental health problem, when issues related to psychosocial
      problems were discussed during the visit, when the youth demonstrated mental
      health symptoms, impairment, or burden to the family, and when the youth was
      older, uninsured, or received Medicaid. Identification was less likely when the
      PCP reported greater burden associated with treating psychosocial problems and
      when the PCP reported greater accessibility to mental health specialists. These
      results suggest that identification is associated with the interaction of
      multilevel factors and that the GPM is a useful model to investigate points of
      intervention for improving the identification of children's mental health
      problems in primary care settings.

PMID- 17226091
TI  - Maternal smoking and infant feeding: breastfeeding is better and safer.
AB  - The rise in smoking rates among young women has implications for children's
      health aggravated in lower social strata where infant morbidity and mortality
      rates are higher. The protection afforded by breastfeeding is beneficial to
      infants in rich and poor countries alike. Women (especially when young,
      uneducated, and unsupported) who are smokers constitute a risk group for
      abandoning breastfeeding; moreover, their bottle-fed newborns run a greater risk
      of morbidity and mortality. Bottle-feeding is attendant on maternal cigarette
      smoking. The advantages of breastfeeding over bottle-feeding are discussed with
      regard to systemic effects and the specific effects of cyanide (which can affect
      the iodine metabolism of infants) and nicotine derived from food and maternal
      smoking. Despite great strides in bans on smoking, public health policies should
      be designed to keep in perspective that breastfeeding is an effective tool to
      counterbalance the health disadvantages that under-privileged infants of smoking
      mothers face. This paper argues that infants born to smoking parents are better
      protected by breastfeeding than by formula feeding. Therefore, if public health
      policies cannot stop addicted mothers from smoking during pregnancy it is
      fundamental not to miss the chance of encouraging and supporting breastfeeding.
      The food and health inequalities of socially disadvantaged groups demand well
      crafted public-health policies to reduce the incidence of diseases and compress
      morbidity: these policies need to make it clear that breastfeeding is better and
      safer.

PMID- 17226092
TI  - Gender similarities and differences in the association between risk and
      protective factors and self-reported serious delinquency.
AB  - Boys consistently report higher rates of serious offending during late
      adolescence than do girls, yet research is mixed regarding the ways in which
      males and females may differentially experience risk and protection in their
      families, schools, peer groups, and as individuals. This article examines gender
      differences in 22 psychosocial risk and protective factors associated with
      serious delinquency. Based on self-reported information from 7,829 10th-grade
      students completing the Communities That Care Youth Survey, all psychosocial
      factors were significantly related to serious delinquency for both sexes. For 12
      of the 22 factors, the strength of the association was significantly greater for
      males, and, for 18 factors, boys reported higher levels of risk exposure and
      lower levels of protection than did girls. Together, these findings suggest that
      boys' greater involvement in serious delinquency is due to the combination of
      experiencing more risk and less protection than girls and the greater association
      of these predictors with serious delinquency for boys compared to girls.
      Implications for prevention programming are discussed.

PMID- 17226093
TI  - Executive inhibitory control and cooperative behavior during early school years:
      a follow-up study.
AB  - Several links between aspects of executive functioning and the development of
      social competence have been established. The present study investigates the
      relation between executive inhibitory control and cooperative/non-cooperative
      behavior, in an ecological setting, and from a longitudinal perspective.
      Elementary school children (n=195) of three age groups (7, 9, 11 years,
      initially) were measured at two consecutive time points, at a one-year interval,
      with tasks tapping executive inhibitory control (the Stroop test), and social
      competence (a collaborative puzzle solving task). Executive inhibition was
      identified as the most influential stable predictor only in the case of non
      cooperative behavior and presented strong concurrent relations with both
      cooperative and non-cooperative behavior at follow-up, even when controlling for
      previous level of the same behavior. The findings imply the need to consider the
      important role of executive inhibitory processes in multifactorial models of
      social competence development and in the refinement of present interventions.

PMID- 17226094
TI  - Homotypic versus heterotypic continuity of anxiety symptoms in young adolescents:
      evidence for distinctions between DSM-IV subtypes.
AB  - OBJECTIVE: to investigate homotypic and heterotypic longitudinal patterns of
      symptoms of separation anxiety disorder (SAD), generalized anxiety disorder
      (GAD), social phobia (SoPh), panic disorder (PD), and obsessive compulsive
      disorder (OCD) in young adolescents from the Dutch general population. METHOD:
      2,067 individuals (51.4% girls) from a Dutch community sample, who were assessed
      for the first time when they were aged 10 to 12 years, were followed up across a
      period of two years. At both assessments, anxiety symptoms were assessed with the
      RCADS, a self-report questionnaire. RESULTS: Regression analyses indicated that
      homotypic continuity was relatively high for SAD, GAD, and SoPh symptoms, and for
      PD in girls. CONCLUSIONS: In many studies, anxiety disorders are treated as one
      group of disorders, and some widely used assessment instruments, such as the
      Child Behavior Checklist, do not even contain scales that tap different anxiety
      dimensions. In the present study, evidence for homotypic continuity was found,
      especially for symptoms of separation, social, and generalized anxiety, and for
      symptoms of panic disorder in girls, underscoring the usefulness of making
      distinctions between different anxiety constructs.

PMID- 17226095
TI  - Examining subtypes of behavior problems among 3-year-old children, Part II:
      investigating differences in parent psychopathology, couple conflict, and other
      family stressors.
AB  - This study examined family stressors among 3-year-old children who were
      classified as hyperactive (HYP), hyperactive and oppositional defiant (HYP/OD),
      and non-problem based on mothers' reports of behavior. Children with HYP/OD were
      found to experience higher levels of family stressors than non-problem children
      on almost every family stressor variable. Compared to children with HYP, families
      of children with HYP/OD also tended to report more Axis II maternal
      psychopathology, Axis I paternal psychopathology, and high intensity couple
      conflict tactics. However, the HYP and HYP/OD group did not significantly differ
      on maternal Axis I psychopathology, paternal Axis II psychopathology, parental
      marital status, negative life events, frequency of couple conflict, or use of
      lower intensity couple conflict tactics. Parents of children with HYP and HYP/OD
      reported more negative life events, more maternal adult ADHD symptoms, and more
      maternal avoidance and verbal aggression during marital conflict than parents of
      non-problem children. Implications for treatment and etiology are discussed.

PMID- 17226096
TI  - Resources and well-being among Arab-American elders.
AB  - This study addresses diversity of aging experiences by examining the associations
      among immigrant status, religious affiliation, and resources in the form of both
      human and social capital with the well-being of Arab-American elders. Data were
      drawn from a face-to-face survey of 101 Arab-American men and women aged 56 and
      over living in the metropolitan Detroit area. Correlations demonstrate that
      religious affiliation is not associated with well-being. Multiple regression
      analyses reveal that U.S. born Arab Americans reported less frequent feelings of
      depression and greater life satisfaction than did immigrants, but this variation
      appears to be accounted for by human capital indicators including education level
      and language. Social capital including perceptions of the ability to confide in
      child and relationship quality with spouse is significantly associated with well
      being, yet does not constitute a pathway to well-being for Arab-American elders.
      Human and social capital represent valuable resources and their distribution
      within this immigrant/ethnic group is associated with noteworthy variations in
      well-being.

PMID- 17226098
TI  - Valproic acid aggravates epilepsy due to MELAS in a patient with an A3243G
      mutation of mitochondrial DNA.
AB  - Epilepsy is one of the most common presentations of patients with mitochondrial
      myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS).
      MELAS is typically caused by an A-to-G substitution at nucleotide position 3243
      of mitochondrial DNA. Valproic acid, a common anticonvulsant, can actually
      increase the frequency of seizures in individuals with MELAS. Here, we report a
      single case-study of a 38-year-old man who presented with focal seizures and had
      MELAS Syndrome due to the A3243G mitochondrial DNA mutation. Manifestation of
      epilepsia partialis continua was aggravated by use of valproic acid. Convulsions
      abated after discontinuation of valproic acid. Our experience suggests that
      valproic acid should be avoided for the treatment of epilepsy in individuals with
      mitochondrial disease.

PMID- 17226099
TI  - Intrastriatal hypoxanthine reduces Na(+),K (+)-ATPase activity and induces
      oxidative stress in the rats.
AB  - The main objective of this study was to investigate the effects of a single
      intrastriatal injection of hypoxanthine, a metabolite accumulated in Lesch Nyhan
      disease and possibly involved in its neuropathology, on Na(+),K(+)-ATPase
      activity, as well as on some parameters of oxidative stress, namely
      chemiluminescence (an index of lipid peroxidation), total radical-trapping
      antioxidant parameter--TRAP (an index of total antioxidant capacity of the
      tissue) and total thiol protein membrane content, in striatum, cerebral cortex
      and hippocampus of rats. Results show that hypoxanthine significantly decreased
      Na(+),K(+)-ATPase activity and TRAP while increased chemiluminescence in all
      ipsislateral structures tested. However, no effect on total thiol protein
      membrane content was detected. We suggest that hypoxanthine induces oxidative
      stress in all cerebral structures studied (striatum, hippocampus and cerebral
      cortex) and that the reduction of Na(+),K(+)-ATPase activity was probably
      mediated by reactive oxygen species.

PMID- 17226100
TI  - High-throughput sorting and analysis of human sperm with a ring-shaped laser
      trap.
AB  - Sperm motility is an important concept in fertility research. To this end, single
      spot laser tweezers have been used to quantitatively analyze the motility of
      individual sperm. However, this method is limited with throughput (single sperm
      per spot), lacks the ability of in-situ sorting based on motility and chemotaxis,
      requires high laser power (hundreds of milliWatts) and can not be used to
      dynamically monitor changes in sperm swimming behavior under the influence of a
      laser beam. Here, we report a continuous 3-D ring-shaped laser trap which could
      be used for multi-level and high-throughput (tens to hundred sperm per ring)
      sperm sorting based on their motility and chemotaxis. Under a laser power of only
      tens of milliWatts, human sperm with low to medium velocity are slowed down,
      stopped, or forced to change their trajectories to swim along the ring due to the
      optical gradient force in the radial direction. This is the first demonstration
      of parallel sperm sorting based on motility with optical trapping technology. In
      addition, by making the sperm swimming along the circumference of the ring, the
      effect of laser radiation, optical force and external obstacles on sperm
      energetics are investigated in a more gentle and quantitative way. The
      application of this method could be extended to motility and bio-tropism studies
      of other self-propelled cells, such as algae and bacteria.

PMID- 17226097
TI  - Immunohistochemical study on distribution of NF-kappaB and p53 in gerbil
      hippocampus after transient cerebral ischemia: effect of pitavastatin.
AB  - We investigated the immunohistochemical alterations of the transcription nuclear
      factor kappa-B (NF-kappaB) and transcription factor p53 in the hippocampus after
      transient cerebral ischemia in gerbils. We also examined the effect of 3-hydroxy
      3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the
      alterations of NF-kappaB, p53 and neuronal nuclei in the hippocampus after
      ischemia. Severe neuronal damage was observed in the hippocampal CA1 neurons 5
      and 14 days after ischemia. In the present study, the increase of NF-kappaB
      immunoreactivity in glial cells and p53 immunoreactivity in neurons preceded
      neuronal damage in the hippocampal CA1 sector after ischemia. Thereafter, NF
      kappaB immunoreactivity was induced highly in reactive astrocytes and microglia
      of the hippocampal CA1 sector where severe neuronal damage was observed. Our
      immunohistochemical study showed that pitavastatin prevented the alterations of
      NF-kappaB and p53 in the hippocampal CA1 sector 5 days after transient ischemia.
      Furthermore, our results with neuronal nuclei immunostaining indicate that
      pitavastatin dose-dependently prevented the neuronal cell death in the
      hippocampal CA1 sector 5 days after transient cerebral ischemia. These results
      suggest that the up-regulations of NF-kappaB in glia and p53 in neurons can cause
      neuronal cell death after ischemia. Our findings also support the hypothesis that
      NF-kappaB- and/or p53-mediated neuronal cell death is prevented through
      decreasing oxidative stress by pitavastatin. Thus, NF-kappaB and p53 may provide
      an attractive target for the development of novel therapeutic approaches for
      brain stroke.

PMID- 17226102
TI  - Intravenous drug self-administration in mice: practical considerations.
AB  - Chronic intravenous drug self-administration in rodents is a useful procedure for
      predicting the abuse liability of novel drugs in humans, for evaluating candidate
      treatments for drug abuse and dependence, and for studying the biological basis
      of addiction. Despite the technical challenge in achieving chronic self
      administration behavior in the mouse species, researchers are increasingly using
      genetically engineered mice to investigate the role of specific genes in abuse
      related effects of drugs. This review focuses on recent technical innovations as
      well as theoretical considerations for comparing intravenous (i.v.) drug self
      administration behavior between mouse strains, including mice with targeted
      mutations. Part I of the present article describes techniques for successfully
      conducting self-administration studies in mice, including advantages,
      disadvantages and possible implications of employing various experimental
      approaches. Part II provides a review of recent data that address how the genetic
      background on which mutations are expressed may influence results from gene
      targeting studies.

PMID- 17226101
TI  - Chemical validation of molecular mimicry: interaction of cholera toxin with
      Campylobacter lipooligosaccharides.
AB  - It is generally believed that molecular mimicry between bacterial
      lipooligosaccharide (LOS) and nerve glycolipids may play an important pathogenic
      role in immune-mediated peripheral neuropathy. One of the putative infectious
      agents is Campylobacter jejuni (C. jejuni). To elucidate the structural basis for
      the molecular mimicry, we investigated the structure of the lipooligosaccharide
      (LOS) fraction of C. jejuni, strain HS19, and found that it includes at least two
      components, characterized as fast-and slow-moving bands (LF and LS) by thin-layer
      chromatography as revealed by cholera toxin B subunit (Ctxb) overlay. Structural
      analysis of the oligosaccharide portion of LS established that it had the
      following structure: Gal-GalNAc-(NeuAc)Gal-Hep-(Glc;PO(3)H)Hep-Kdo. The GM1-like
      epitope was validated by a terminal tetrasaccharide unit within this structure.
      On the other hand, analysis of LF revealed an entirely different structure: 1, 4'
      bisphosphoryl glucosamine disaccharide N, N'-acylated by 3-(2
      hydroxytetracosanoyloxy)octadecanoic acid at 2- and 2'-positions, which is
      consistent with that of lipid A. No GM1-like epitope was observed in LF. Both LS
      and LF interacted with Ctxb as demonstrated by TLC-overlay and sucrose density
      gradient centrifugation. Surprisingly, LF does not have the basic GM1 structure
      for interacting with Ctxb. Instead, the affinity of LF to Ctxb required that one
      or both of the phosphate groups be present in the glucosamine disaccharide
      residue because after alkaline phosphatase treatment the dephosphorylated LF was
      unable to bind to Ctxb. We conclude that LS is likely the component contributing
      to GM1-mimicry in autoimmune peripheral neuropathy and that the role of LF is not
      clear but may be associated with the initial activation of autoreactive T cells.

PMID- 17226103
TI  - Use of a novel mouse genotype to model acute benzodiazepine withdrawal.
AB  - Withdrawal from benzodiazepines in physically dependent rodents often requires
      that the drug be dislodged from its receptor with a competitive antagonist.
      Withdrawal Seizure-Prone (WSP) mice were selectively bred for their
      susceptibility to handling-induced withdrawal convulsions following chronic
      treatment with ethanol. Reflecting pleiotropic genetic influences, they also
      experience more severe withdrawal from other sedative-hypnotics including the
      benzodiazepine, diazepam. We used this susceptible genotype to test whether other
      benzodiazepine receptor (BZR) agonists also produce physical dependence following
      acute administration, comparing studies of spontaneous withdrawal with those
      where convulsions were precipitated by a BZR antagonist (flumazenil). Separate
      groups of mice were tested following a single injection of one of eight BZR
      agonists. Several doses of each drug were tested for spontaneous withdrawal, and
      a single dose of each drug was tested for precipitated withdrawal. Withdrawal
      convulsions were seen after all of the drugs by at least one method, suggesting
      that BZR agonists as a class elicit acute physical dependence in this susceptible
      genotype.

PMID- 17226105
TI  - Adiponectin and cardiovascular mortality: evidence for "reverse epidemiology".

PMID- 17226106
TI  - Adrenomedullin gene expression and peptide levels in the heart and blood vessels
      of streptozotocin-diabetic rats.
AB  - The aim of the present study was to assess the changes in gene expression and
      peptide adrenomedullin (AM) levels in cardiovascular and other tissues in the
      streptozotocin-diabetic rats. For this purpose, diabetes was induced by
      intraperitoneal injection of streptozotocin (STZ, 65 mg/Kg body weight). Half of
      the diabetic rats were subcutaneously injected with insulin in the afternoon (4
      units/day) one week after STZ injection until the day before killing. Control
      rats received only saline injection. AM mRNA was determined in cardiovascular and
      other tissues of streptozotocin-diabetic rats using solution-hybridization-RNase
      protection assay. Circulating AM and peptide AM in cardiovascular and other
      tissues were estimated using a specific radioimmunoassay. There were increases in
      preproAM mRNA levels in the left and right ventricles and in the thoracic aorta
      in both the 2-week and 4-week diabetic rats, but not in the two atria, the
      mesenteric artery and the lung. In the 2-week diabetic rats, there were decreases
      in AM contents in the two atria and the lung but an increase in the thoracic
      aorta. In the 4-week diabetic rats, there were bigger decreases in the atria and
      also a decrease in the left ventricle. The plasma AM levels were not changed but
      there was an increase in the excretion of AM in the urine. Our results suggest a
      possible increase in AM release in the heart and the thoracic aorta in the 2-week
      and 4-week diabetic rats.

PMID- 17226107
TI  - Antiproliferative effect of adiponectin on MCF7 breast cancer cells: a potential
      hormonal link between obesity and cancer.
AB  - Adiponectin, a hormone secreted by adipose tissue, circulates at high
      concentrations in human plasma. Paradoxically, plasma levels of adiponectin are
      approximately 50% lower in obese than in lean subjects. An association between
      low plasma levels of adiponectin and higher risk of developing breast and other
      cancers was recently reported. Obesity and overweight have also been associated
      with increased mortality from cancer. To test the hypothesis that adiponectin
      exerts direct antiproliferative and/or pro-apoptotic effects on cancer cells, we
      used the MCF7 human breast adenocarcinoma cell line. The proliferation rate of
      the MCF7 cells was measured using the MTT method, while apoptosis was examined by
      quantifying the DNA fragmentation using an ELISA assay. In addition, adiponectin
      receptor 1 (AdipoR1) and AdipoR2 mRNA expression was detected using RT-PCR.
      Adiponectin diminished the proliferation rate of MCF7 cells; this effect was
      significant after 48-96 hours of treatment. The presence of receptor expression
      suggested that the effect of adiponectin on cell proliferation was most likely
      specific and adiponectin receptor-mediated. Adiponectin induced no apoptosis of
      MCF7 cells over 48 hours. We conclude that adiponectin inhibits proliferation but
      causes no apoptosis of MCF7 breast cancer cells. These data suggest that
      adiponectin may represent a direct hormonal link between obesity and cancer.

PMID- 17226108
TI  - Inhibition of peroxidase and catalase activities and modulation of hydrogen
      peroxide level by inositol phosphoglycan-like compounds.
AB  - Inositol phosphoglycan-like compounds are produced by the hydrolysis of the
      membrane bound glycosyl phosphoinositides. Besides being short term mediators of
      insulin action, they inhibit peroxidases and catalase, increasing the
      concentration of cellular hydrogen peroxide. Although high concentrations of
      hydrogen peroxide are toxic, moderate increases of its basal level are signals
      for different metabolic pathways. The inhibitor, localized in the cytosol of the
      cell, acts on peroxidases and catalase of the same tissue (homologous action) and
      of other tissues or organisms (heterologous action). The inositol phosphoglycan
      like compound inhibits peroxidases with different prosthetic groups, i.e.
      containing iron such as: thyroid peroxidase, lactoperoxidase, horseradish
      peroxidase, soy bean peroxidase; and containing selenium such as glutathione
      peroxidase and 2-cys peroxiredoxin with no prosthetic group. Besides peroxidases,
      the inositol phosphoglycan-like compound inhibits catalase, another heme enzyme.
      The inhibition kinetics demonstrates a noncompetitive effect. The site of action
      is not the prosthetic group, given that the inhibitor does not produce any effect
      on the peak in the Soret region in the presence or absence of hydrogen peroxide.
      In conclusion, the inositol phosphoglycan-like compound is the general inhibitor
      of peroxidases and catalase involved in the modulation of hydrogen peroxide level
      that acts in different metabolic pathways as a signal transducer.

PMID- 17226109
TI  - The effect of chronic nicotine administration on bone mineral content and bone
      strength in normal and castrated male rats.
AB  - Tobacco, containing nicotine as the principal pharmacologically active chemical,
      has been identified as being a risk factor for the development of osteoporosis.
      Thirty-two male Wistar rats of two months of age were castrated or sham operated
      to evaluate the effects of long-term administration (four months) of nicotine in
      drinking water (9.0 mg/kg/day). The presence of cotinine in urine confirmed
      successful delivery of nicotine. The bones were tested mechanically by a three
      point bending test in a Mini Bionix (MTA) testing system. The bones from
      castrated rats were characterized by a reduction in bone density as well as ash,
      calcium and phosphate content. Castration significantly altered mechanical
      properties of bone (9%) and femoral cortical thickness. When intact rats were
      treated with a high dose of nicotine, nicotine had negative effect on tibial bone
      density as well as ash, calcium, phosphate content and significantly altered the
      mechanical properties of bone (12%) and femoral cortical thickness compared to
      intact animals. Nicotine itself does not exert any anti-androgenic effect and
      does not produce changes in the weight of seminal vesicles. Nicotine-induced bone
      loss is associated with high bone turnover in the male rats as expressed by
      increased TrACP and B-ALP. When castrated rats were treated with the high dose of
      nicotine the changes in bone density resulting from castration were not further
      potentiated. These results document the efficacy of nicotine at high doses to
      cause bone loss and loss of bone mechanical strength in intact rats. The results
      of the present study may be interpreted as supporting the hypothesis of nicotine
      as a risk factor for osteoporosis.

PMID- 17226110
TI  - Circulating serum adiponectin concentrations do not differ between obese and non
      obese caucasians and are unrelated to insulin sensitivity.
AB  - Reduced serum levels of adiponectin in obesity and insulin resistance seem
      paradoxical, since adipose tissue is the only source of adiponectin, and reports
      on that subject are contradictory. The aim of this study was to investigate the
      concentrations of adiponectin in non-obese and obese normoglycemic humans, and to
      determine the correlation between adiponectin and HOMA index of insulin
      sensitivity. Based on the WHO definition of obesity, 145 obese subjects and 49
      non-obese controls (aged 20-55 years) were studied. The serum adiponectin
      concentrations did not differ between subjects and controls (p=0.6398) and were
      not correlated with HOMA index (r=-0.0211; p=0.8048, and r=-0.0523; p=0.4757, for
      subjects and controls, respectively). Adiponectin was not correlated with HOMA
      index in females (r=-0.0521; p=0.6546, and r=-0.0825; p=0.3981, for female
      subjects and controls, respectively) as well as in males (r=0.0033; p=0.9791, and
      r=0.0123; p=0.9131, for male subjects and controls, respectively). These results
      lead to the conclusion that neither the concentrations of adiponectin differ
      between obese and non-obese humans, nor does any relationship between adiponectin
      concentration and insulin sensitivity exist.

PMID- 17226111
TI  - Critical evaluation of methods for determination of body fat content in children:
      back to basic parameters?
AB  - Considering the increasing prevalence of obesity among children and of obesity
      related disorders in the pediatric population, the reliable evaluation of body
      fat content in children is of critical importance in research and clinical
      medicine. In this study, we assessed the congruency of different estimates for
      body fat content in prepubertal children. We determined anthropometric
      parameters, such as BMI and skinfold thickness, and bioelectrical impedance in
      676 prepubertal Caucasian children. We calculated body fat percentage (BF%) from
      these parameters applying 5 distinct algorithms and established raw centiles for
      these models. Expectedly, girls had significantly higher BF% regardless of the
      method applied. There were, however, significant variances in the calculated
      amount of BF% between the algorithms, with BIA based equations giving highest
      BF%, while skinfold based equations tended to provide lower BF% values. Direct
      comparison of the algorithms revealed a high degree of inconsistency and poor
      agreement in the assessment of body fat with variations of >10% BF%. Great
      differences in basic parameters, such as DeltaBMI (3.2 kg/m (2)) or
      Deltaskinfolds (1.75-fold), would be needed to reliably predict correct ranking
      of 10% difference in body fat with 95% probability. In summary, BF% strongly
      varies depending on both the method as well as the algorithm used. This questions
      the applicability of such field methods for the assessment of BF% for comparative
      analyses and the superiority of information over basic parameters such as BMI.

PMID- 17226112
TI  - Factors responsible for glucose intolerance in Japanese subjects with impaired
      fasting glucose.
AB  - Impaired fasting glucose (IFG) represents risk of development of diabetes (DM)
      and its complications. We investigated insulin secretion and insulin sensitivity
      in 403 IFG subjects divided into three levels of 2-hour postchallenge glucose (2
      h PG) to clarify the factors responsible in the development of glucose
      intolerance in Japanese IFG. Nearly 60% of the subjects at annual medical check
      up with FPG of 6.1-7.0 mmol/l at the first screening were diagnosed by 75 g oral
      glucose tolerance test (OGTT) to have impaired glucose tolerance (IGT; FPG <7.0
      mmol/l and 7.8 mmol/l <2-h PG <11.1 mmol/l) or DM (isolated postchallenge
      hyperglycemia (IPH); FPG <7.0 mmol/l and 11.1 mmol/l <2-h PG level). The primary
      factor in the decreased glucose tolerance was a decrease in early-phase insulin,
      with some contribution of increasing insulin resistance. In addition, IFG/IGT and
      IFG/IPH subjects showed a compensatory increase in basal insulin secretion
      sufficient to keep FPG levels within the non-diabetic range. IFG is composed of
      three different categories in basal, early-phase insulin secretion, and insulin
      sensitivity.

PMID- 17226113
TI  - Variants of the transcription factor 7-like 2 gene (TCF7L2) are strongly
      associated with type 2 diabetes but not with the metabolic syndrome in the
      MONICA/KORA surveys.
AB  - Recently, significant associations between common variants of the transcription
      factor 7-like 2 gene ( TCF7L2) and type 2 diabetes have been reported. This study
      was designed to replicate the reported associations of the two highly correlated
      (r (2)=0.86) TCF7L2 single nucleotide polymorphisms rs12255372 and rs7903146 with
      type 2 diabetes in a case-control study of 2369 MONICA/KORA participants (678
      cases/1691 controls from Augsburg, Germany). To further investigate the
      pathogenic mechanism underlying these associations, we extended our analyses to
      the metabolic syndrome (IDF, NCEP definitions) and its components in a population
      based study comprising 1404 male and female KORA participants aged 55-74 years.
      Results of our analyses strongly confirmed the minor T alleles as risk variants
      for type 2 diabetes (rs7903146: OR (TvsC) [95% CI]=1.36 [1.18;1.58], p=0.00003,
      and rs12255372: OR (TvsG) [95% CI]=1.31 [1.13;1.51], p=0.0003). Moreover, the T
      allele at rs7903146 was inversely associated with log-transformed, HOMA-%B (beta=
      0.07, p=0.005) as a measure of basal insulin secretion, and log-transformed
      fasting insulin (beta=-0.06, p=0.02). No association was found with insulin
      resistance (HOMA-IR) and the metabolic syndrome. These findings support
      replication evidence that TCF7L2 variants increase type 2 diabetes risk. TCF7L2
      may primarily affect pancreatic beta cell function.

PMID- 17226114
TI  - Positive correlation of galanin with glucose in healthy volunteers during an oral
      glucose tolerance test.
AB  - Galanin has been found in increased amounts in subjects with type 2 diabetes. The
      purpose of the present study was to determine the levels of galanin in healthy
      volunteers during an oral glucose tolerance test (OGTT). We enrolled 11 healthy
      volunteers, 4 males aged 48+/-3.56 years with BMI 27+/-0.5 kg/m (2) and 7 females
      aged 41.3+/-3.05 years with BMI 27.6+/-0.9 kg/m (2). All were in good health
      without cardiac, hepatic, renal or other chronic disease. None were taking any
      medication affecting glucose tolerance (beta-blockers, thiazide diuretics, and
      corticoids) and none had a first degree relative with type 2 diabetes. Glucose
      tolerance was determined by using the International Expert Committee criteria.
      Blood samples were collected at 0, 30, 60, 90, 120 and 180 minutes for the
      measurement of plasma glucose, insulin, C-peptide and human galanin (hGal).
      During the OGTT, hGal exhibited a significant increase from time 0 to 90 minutes
      (p < 0.001) and returned to the basal values at 180 minutes, while a positive
      correlation of blood glucose with hGal was observed during the time scale of
      OGTT. A significant increase was detected both in insulin and C-peptide from the
      early beginning of the test at 30 minutes, which remained steady until 90
      minutes, and returned gradually to the basal values at 180 minutes. No
      relationship was found either between hGal and serum insulin, or between hGal and
      serum C-peptide among the healthy subjects, during the OGTT.

PMID- 17226115
TI  - Improved prediction of relapse of Graves' thyrotoxicosis by combined
      determination of TSH receptor and thyroperoxidase antibodies.
AB  - BACKGROUND: Recently, we and others have demonstrated that high levels of auto
      antibodies to the human TSH-receptor (TRAb) predict relapse of hyperthyroidism in
      Graves' disease (GD). Our objective was to extend the outcome of the prediction
      by combining TRAb with thyroperoxidase antibody (TPO-Ab) measurement. PATIENTS
      AND METHODS: One hundred and thirty-one GD patients (118 females, 13 males) were
      analysed, of whom 94 patients (71.8%) had relapse, whereas 37 (28.2%) went into
      remission. Second generation TRAb and TPO-Ab assays were performed in GD patients
      with relapse and remission in mean 4.3 months after initial diagnosis. RESULTS:
      The mean anti-TPO-Ab levels were similar in all patients with relapse and
      remission. However, there was a steady decline from 4047 U/ml to 530 U/ml in the
      remission group that correlated positively with TRAb values (>2 to >10 IU/l). The
      relapse group remained at consistently high levels. The positive predictive value
      (PPV) for relapse in patients with TRAbs >6 IU/l and anti-TPO-Abs >5000 U/ml was
      100, whereas TRAbs >6 IU/l and anti-TPO-Abs >500 U/ml were associated with a PPV
      of 93.7 up to 96 (p=0.008). These Ab constellations accounted for about one third
      of all GD patients. For patients with TRAbs between >2 and <6 IU/l the PPV was
      66.7-90.0. CONCLUSION: Our follow-up analysis indicates that the prediction of
      relapse of GD can be improved by a combined measurement of TRAb and TPO-Ab. In
      patients with moderately increased Abs, determined about 6 months after initial
      diagnosis, an ablative therapy can be approached without delay.

PMID- 17226117
TI  - Comparison of the mitogenic potency of regular human insulin and its analogue
      glargine in normal and transformed human breast epithelial cells.

PMID- 17226116
TI  - Glucose transporter GLUT8 mRNA expression in intestinal Caco-2 cells is regulated
      by growth and metabolism.

PMID- 17226118
TI  - Identification of Some Prostanoids in Aloe vera Extracts.
AB  - Screening of extracts from ALOE VERA revealed the presence of endogenous
      arachidonic acid, a potential precursor for the prostanoids synthesis. The
      presence of endogenous cyclooxygenase, in the plant extracts, was established by
      radiometric assay. Relatively high proportions of PGE (2) and TXB (2) and low
      proportions of other prostaglandins were identified in the plant extract when
      incubated with [ (14)C]-arachidonic acid. Other lipids present in this plant were
      examined and a high percentage of phosphatidylcholine and cholesterol was
      established. Possible importance of prostaglandins formed endogenously by the
      plant is discussed.

PMID- 17226120
TI  - Aescin Content in Embryogenic Callus and in Embryoids from Leaf Explants of
      Aesculus hippocastanum.
AB  - HPLC determinations of the aescin contents in calli and embryoids from leaf
      explants of AESCULUS HIPPOCASTANUM L. were carried out in order to determine
      whether it was possible to obtain aescin-forming proliferations IN VITRO. The
      results indicate that embryogenic calli and embryoids derived from them produce
      an amount of active principle higher than that of horse-chestnut seeds. The data
      are discussed in terms of the relation between tissue differentiation and
      secondary metabolites biosynthesis.

PMID- 17226121
TI  - Cryopreservation of Papaver somniferum Cell Suspension Cultures*.
AB  - The effect of culture age and various cooling rates on the survival and regrowth
      of cryopreserved cell cultures of PAPAVER SOMNIFERUM L. is described. Survival
      and regrowth following cryopreservation, in liquid nitrogen, occurred only with 4
      and 5 day old cultures. No regrowth was observed in 3 or 6 day old cultures.
      Cooling rate had a significant effect on survival following cryopreservation with
      an optimum cooling rate of 0.5 degrees C min (-1).

PMID- 17226119
TI  - Method of Harvesting the Crude Drug Based on Distribution of Alkaloids in the
      Hook and in the Stem with Hook of Uncaria rhynchophylla1.
AB  - The distribution of the content of the pharmacologically active oxindole
      alkaloids in the hook and in the stem of the crude drug "Cho-to-ko" (dried stem
      with hooks of UNCARIA RHYNCHOPHYLLA) prepared from the cultivated plants were
      investigated. The total oxindole alkaloid content of the stem was similar to that
      of the hook portion. It was also found that the area closest to the hook showed a
      slightly higher alkaloid content than the hook, and that the content of the
      oxindole alkaloid tended to decrease as the distance from the hook increased.
      Therefore, the presence of the hook does not affect the quality of the crude drug
      as far as the oxindole alkaloid content is concerned.

PMID- 17226122
TI  - New Eudesmanolides Related to Torrentin from Artemisia herba-alba subsp.
      valentina.
AB  - The reinvestigation of aerial parts of A. HERBA-ALBA subsp. VALENTINA afforded
      four new eudesmanolides, all of them closely related to torrentin. Their
      structures were deduced by spectroscopic and chemical methods.

PMID- 17226123
TI  - Volatile Constituents of Origanum dubium Leaves and Stem-Bark.
AB  - The compositions of the essential oil of the leaves and stem-bark of ORIGANUM
      DUBIUM Boiss (Labiatae) were analysed for the first time by means of gas
      chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). A total of
      forty-one components were identified; qualitative and quantitative differences in
      the oil compositions were observed. The major constituents of the leaf oil were
      1,8-cineole, linalool, and camphor while gamma-cadinene, linalool, beta
      farnesene, and delta-cadinene were major components of the stem-bark oil.

PMID- 17226124
TI  - Iridoids and an Alkaloid from Oxera morieri1.
AB  - A novel monoterpene alkaloid, oxerine, has been isolated from the aerial parts of
      OXERA MORIERI. Its structure 7 has been elucidated on the basis of its spectral
      data and its sterochemistry established by its synthesis, using harpagide as
      starting material. Five iridoids and verbascoside have also been isolated from
      the plant material.

PMID- 17226125
TI  - Gravacridondiolacetate, A New Dihydrofuroacridone Alkaloid from Ruta graveolens.

PMID- 17226126
TI  - Flavonoids from the Aboveground Parts of Ruscus aculeatus.

PMID- 17226127
TI  - Terpenic Constituents from Icacina senegalensis.

PMID- 17226128
TI  - Kadsulactone and kadsudilactone, two new triterpenoid lactones from kadsura
      species.

PMID- 17226129
TI  - Constituents of the Essential Oil from Melissa officinalis.

PMID- 17226130
TI  - Constituents of the Essential Oil of the Fruits of Zanthoxylum bungeanum.

PMID- 17226131
TI  - The Essential Oil from Tanacetum millefolium.

PMID- 17226132
TI  - Studies on the Chemical Constituents of Premna fulva.

PMID- 17226133
TI  - Phaseoluside-A, A New Soyasapogenol B Triglucoside from Phaseolus vulgaris Seeds.

PMID- 17226134
TI  - Neolignans and Lignans of Nardostachys jatamansi Roots1.

PMID- 17226135
TI  - Polyacetylenes from the Underground Parts of Cichorium intybus.

PMID- 17226136
TI  - Isolation of trans-Phytol from Phyllanthus niruri1.

PMID- 17226137
TI  - In Vitro Production of Essential Oil from Proliferating Shoots of Rosmarinus
      officinalis1.
AB  - The 40-day-old IN VITRO proliferating shoots of ROSMARINUS OFFICINALIS L. var.
      GENUINA forma ERECTUS produced an appreciable quantity of essential oil, i.e.,
      1.8% fw, which was similar in its constituents to that obtained from 1-year-old
      plants, whether naturally grown or IN VITRO-raised potted plants. However, the
      quantity of various constituents identified so far was generally, but marginally,
      less in the former case than the latter two kinds of 1-year-old plants with the
      exception of bornyl acetate and 1,8-cineole, the concentrations of which were
      higher in the proliferated shoots than the plants. The essential oil content of 1
      year-old naturally grown plants was 2.4% fw, while it was 2.38% fw in the IN
      VITRO-raised potted plants of the same age.

PMID- 17226138
TI  - Thermospray Liquid Chromatography/Mass Spectrometry (TSP LC/MS) Analysis of the
      Alkaloids from Cinchona in vitro Cultures.
AB  - The alkaloids from CINCHONA LEDGERIANA shoot cultures and from CINCHONA ROBUSTA
      shoot cultures and a compact globular structure (CGS) culture were analyzed by
      thermospray liquid chromatography/mass spectrometry (TSP LC/MS). Because of the
      relative stability of the alkaloids under TSP discharge ionization conditions, a
      protonated molecule was observed in the mass spectra with hardly any
      fragmentation. When the reference compounds were available, the knowledge of the
      molecular mass and of the retention time was sufficient to identify most of the
      alkaloids. HPLC with UV photodiode-array detection complemented LC/MS perfectly
      by providing information about the aromatic part of the alkaloids (structure and
      substitution pattern). New alkaloids detected in CINCHONA IN VITRO cultures were
      5-methoxytryptamine and corynantheal. In order to determine whether 5
      methoxytryptamine was a precursor of the methoxylated quinolines, this indole was
      incubated with secologanin and several CINCHONA ROBUSTA crude protein extracts.
      Under all conditions tested, the coupling of 5-methoxytryptamine with secologanin
      remained unsuccessful. Only tryptamine condensed with secologanin to yield
      strictosidine. These results indicate that CINCHONA cells are able to methoxylate
      simple indoles like tryptamine and that 5-methoxytryptamine is very likely not
      used for the subsequent biosynthesis of the methoxylated quinolines.

PMID- 17226139
TI  - Isolation and 2D NMR Studies of Alkaloids from Comptonella sessilifoliola1.
AB  - Six known furanoquinoline alkaloids have been isolated from the wood and trunk
      bark of COMPTONELLA SESSILIFOLIOLA (Guillaumin) Hartley (Rutaceae). 2D NMR
      experiments gave the assignment of all the signals for both (1)H- and (13)C-NMR
      spectra. Pteleine and kokusaginine were used as models. The two-dimensional
      carbon-proton correlation experiments, performed for the first time on
      furanoquinoline alkaloids, led us to correct (13)C-NMR assignments previously
      described in the literature.

PMID- 17226140
TI  - Chemical Study on the Alkaloids of Corydalis hsuchowensis.
AB  - Ten alkaloids were isolated from the bulb of CORYDALIS HSUCHOWENSIS W. Y. Lian
      nov. ined. Among them nine alkaloids are known, identified as (-)-stylopine ( 1),
      cheilanthifoline ( 2), (+)-adlumidine ( 3), (+)-bicuculline ( 4), sibiricine (
      5), humosine A ( 6), (+)-bulbocapnine ( 7), (-)-scoulerine ( 8), and protopine (
      10), respectively. The other one is a new isoquinoline alkaloid. The structure
      was deduced as 9 based on spectroscopic analysis and chemical reactions. It was
      named coryximine.

PMID- 17226141
TI  - Subalpinoside (S1), an Unknown Oleandrigenin Glycoside and Other Cardenol from
      Digitalis subalpina var. subalpina.
AB  - From the leaves of DIGITALIS SUBALPINA Br.-Bl. var. SUBALPINA an oleandrigenin
      glycoside was isolated as the main cardiotonic compound besides some known
      glycosides such as evatromonoside, lanatoside A and B, gitoroside, and others.
      The structure of this compound was elucidated by spectroscopic methods ( (1)H-,
      (13)C-, 2D-NMR spectroscopy) as gluco-oleandrigenin digitoxoside. This is the
      first report of the occurrence of oleandrigenin derivatives in a DIGITALIS
      species.

PMID- 17226142
TI  - A New Triterpenoid and its Glycoside from Phytolacca esculenta.
AB  - A new triterpenoid and its glycoside, designated as esculentagenic acid and
      esculentoside J, have been isolated and characterized from the roots of
      PHYTOLACCA ESCULENTA. The new compounds have been identified as 2beta,3beta,23,30
      tetrahydroxyolean-12-en-28-oic acid and 3- O-[beta- D-glucopyranosyl(1-->4)-beta-
      D-xylopyranosyl] - 28- O-beta- D-glucopyranosyl- 2beta,3beta,23,30
      tetrahydroxyolean-12-en-28-oic acid.

PMID- 17226143
TI  - Glyyunnansapogenins G and H: Two New Pentacyclic Triterpenoids of the 18alphaH
      Oleana-9(11),12-diene Type from Glycyrrhiza yunnanensis Roots.
AB  - Two new pentacyclic triterpenoid sapogenins of the 18alpha H-oleana-9(11),12
      diene type named glyyunnansapogenins G and H were isolated from the roots of
      GLYCYRRHIZA YUNNANENSIS Cheng f. et L. K. Tai. Their structures were elucidated
      as 18alpha H-oleana-9(11),12-diene-3beta,21alpha,29-triol and 18alpha H
      3beta,21alpha-dihydroxyoleana-9(11),12-dien-29-oic acid, respectively, by
      spectroscopic methods. This is the first report of the occurrence of the 18alpha
      H series of oleana-9(11),12-diene compounds in nature.

PMID- 17226144
TI  - Three New Dibenzocyclooctadiene Lignans from Kadsura longipedunculata.
AB  - Five dibenzocyclooctadiene lignans were isolated from the stems of KADSURA
      LONGIPEDUNCULATA collected in Guangxi province. Three of them are new compounds,
      named benzoyl-, isovaleroyl-, and isobutyroylbinankadsurin A. Binankadsurin A was
      isolated from nature for the first time. The absolute configuration of
      isovaleroyloxokadsurane, a spirobenzofuranoid lignan from K. COCCINEA, was
      confirmed by chemical correlation with isovaleroylbinankadsurin A.

PMID- 17226145
TI  - Structures of Four New Isoprenylated Xanthones, Cudraxanthones L, M, N, and O
      from Cudrania tricuspidata1,2.
AB  - Four new isoprenylated xanthones, cudraxanthones L, M, N, and O were isolated
      from the ethanol extract of the root bark of CUDRANIA TRICUSPIDATA (Carr.) Bur.
      (Moraceae), collected in China. The structures of cudraxanthones L, M, N, and O
      were shown to be 1-4, respectively, on the basis of chemical and spectral
      evidences.

PMID- 17226146
TI  - Qualitative and Quantitative Analysis of the Phenolic Constituents from
      Orthosiphon aristatus.
AB  - ORTHOSIPHON ARISTATUS (Orthosiphonis folium DAB 9) was studied with regard to its
      phenolic constituents. Twenty compounds were isolated and identified on the basis
      of their spectral characteristics. The compounds included nine lipophilic
      flavones, two flavonol glycosides, and nine caffeic acid derivatives. The
      presence of the recently reported methylripariochromene A could not be confirmed.
      All compounds identified were quantified by HPLC. The caffeic acid derivatives
      including the major compounds rosmarinic acid and 2,3-dicaffeoyltartaric acid
      (67% of total identified phenolics) predominated over the flavones (33%) in an
      aqueous MeOH extract. The predominance of the caffeic acid derivatives was even
      more pronounced in a hot water extract (94.5% of total identified phenolics) that
      was comparable to a herbal tea.

PMID- 17226147
TI  - Exaltoside and 7-Epiexaltoside, Two Novel Acylated Secoiridoid Glucosides from
      Villarsia exaltata*.
AB  - Aerial parts of VILLARSIA EXALTATA (Menyanthaceae) were investigated for
      secoiridoids. Two new acylated compounds of the "foliamenthintype", named
      exaltoside and 7-epiexaltoside, have been isolated and structurally elucidated by
      spectroscopic means ( (1)H-, (13)C-NMR, COSY, FAB and FD mass spectrometry).

PMID- 17226148
TI  - Iridoid Glucosides from Penstemon nitidus.
AB  - From the leaves of PENSTEMON NITIDUS Dougl. (smooth blue beardtongue) besides the
      known iridoid glucosides cornin (syn. verbenalin), hastatoside and beta
      dihydrohastatoside the new compound 10-hydroxycornin has been isolated. The
      structures of all compounds were established by spectroscopic means (FD-MS, (1)H
      , (13)C-, 2D-NMR, and NOE). This is the first report of cornin and analogous 6
      keto iridoids in scrophulariaceous plants. Up to now iridoid glucosides like
      these have only been found in plants belonging to the Cornaceae and its allies
      and to the Lamiaceae-Verbenaceae complex.

PMID- 17226149
TI  - 5''-Hydroxydigipenstroside and Penstriatoside: Novel Dimeric and Trimeric Open
      Chain Monoterpene Glucosides from Penstemon digitalis*.
AB  - A new dimeric open-chain monoterpene glucoside, 5''-hydroxydigipenstroside {1
      beta- D-glucopyranosyl)-8-[5'',8''-dihydroxy-2'',6''-dimethyl-2''( E),6''( E)
      octadienoyl]-5,8-dihydroxy-2,6-dimethyl-2( E),6( E)-octadienoate} has been
      isolated from leaves of PENSTEMON DIGITALIS Nutt. In addition, the novel trimeric
      open-chain monoterpene glucoside penstriatoside {1-(beta- D-glucopyranosyl)-8
      [5'',8''-dihydroxy-2'',6''-dimethyl-2''( E),6''( E)-octadienoyl-8''-(5''',8'''
      dihydroxy-2''',6'''-dimethyl-2''' ( E)6'''( E)-octadienoyl)]-5,8-dihydroxy-2,6
      dimethyl-2 ( E),6( E)-octadienoate} has been encountered. The structures of both
      compounds have been elucidated by spectroscopic means (FD-, FAB-mass, (1)H-,
      (13)C-NMR, COSY, DEPT).

PMID- 17226150
TI  - Guaianolides from Lactuca saligna.
AB  - The phytochemical investigation of the aerial parts of LACTUCA SALIGNA L.
      revealed the presence of lactucin, lactucopicrin, and a new guaianolide named
      11beta,13-dihydrolactucopicrin. The structural configuration was established
      through spectral data.

PMID- 17226151
TI  - Flavonoids and Sesquiterpene Lactones of Artemisia mesatlantica.

PMID- 17226153
TI  - Hamelia patens: A New Source of Ephedrine1.

PMID- 17226152
TI  - 1-n-Butyl-beta-D-fructopyranoside from Liriope spicata var. prolifera.

PMID- 17226154
TI  - Isolation of an Aglycone from Opilia celtidifolia: 3beta-Acetoxyolean-12-ene
      23alpha,28beta-dioic acid.

PMID- 17226155
TI  - Phenylpropanoid Glycosides and Rosmarinic Acid from Momordica balsamina.

PMID- 17226156
TI  - Erratum.

PMID- 17226157
TI  - HPLC analysis of allicin and other thiosulfinates in garlic clove homogenates.
AB  - Reversed-phase high Performance liquid chromatography (C18-HPLC) was used to
      separate and quantitate all the detectable alkyl and alkenyl thiosulfinates,
      including configurational isomers, of garlic homogenates. Pure thiosulfinates
      were synthesized or isolated and identified by (1)H-NMR, and their extinction
      coefficients determined. Some configurational isomers required Separation by
      silica-HPLC. Five previously unreported thiosulfinates have been found, four of
      which contain the TRANS-1-propenyl group and increase several-fold to over half
      the content of allicin upon storage of garlic bulbs at 4 degrees C with a
      concomitant decrease in a gamma-glutamyl peptide. The variation in thiosulfinate
      yield between different countries, stores, bulbs, cloves, and storage times was
      investigated. A method for standardizing the quantitation of allicin yield from
      garlic is proposed and compared to other methods of allicin analysis.

PMID- 17226158
TI  - Genetics of Alkaloids in Papaver somniferum.
AB  - Based on numerical and graphic analyses of 6 x 6 diallele cross progenies (n (2)
      = 36) over two environments, dominance was found to be most prevalent (in
      overdominance range without being inflated by non-allelic interactions) in
      parents for latex yield, and morphine, codeine, thebaine, and narcotine contents.
      However, the additive component was also significant for the former three traits.
      Dominant alleles mostly with positive effects were, by and large, asymmetrically
      distributed in parents except for narcotine content. Heritability estimates were
      moderate and corresponded with low genetic advance estimates for morphine,
      codeine, and thebaine contents. Ample genetic diversity among parents was
      reflected for all traits except narcotine content. On an overall basis, heterosis
      breeding was suggested to be a rewarding proposition for genetic improvement of
      the opium poppy ( PAPAVER SOMNIFERUM L.).

PMID- 17226159
TI  - Diterpenoid Alkaloids from Aconitum vilmorrianum.
AB  - A new diterpenoid alkaloid, vilmorrianone ( 1), has been isolated from ACONITUM
      VILMORRIANUM Kom. The structure was elucidated by spectral methods and confirmed
      by X-ray diffraction analysis. Also four known diterpenoid alkaloids have been
      isolated and identified.

PMID- 17226160
TI  - Medicinal Plants from Papua New Guinea: Graniline-Esters and Germacranolides from
      Blumea arfakiana.
AB  - From the leaves of BLUMEA ARFAKIANA Martelli (Asteraceae), used in traditional
      medicine in Papua New Guinea, besides stigmasterol and beta-eudesmol, four
      graniline esters ( 1-4) have been isolated. Furthermore, blumealactone C ( 5),
      deacetylblumealactone C ( 6), and deoxyblumealactone C ( 7) have been identified.

PMID- 17226161
TI  - Jatamols A and B: Sesquiterpenoids of Nardostachys jatamansi Roots1.
AB  - From the roots and rhizomes of NARDOSTACHYS JATAMANSI, two new eudesmanes
      jatamols A and B were isolated, and their structures were determined by spectral
      analysis and chemical evidence.

PMID- 17226162
TI  - Flavonoids, Phenolic Acids and Coumarins from the Roots of Althaea officinalis.
AB  - From the roots of ALTHAEA OFFICINALIS two flavonoid glycosides were separated.
      Phenolic acids and coumarins were investigated chromatographically. The
      structures of the compounds were established on the basis of acid hydrolysis and
      spectroscopic methods (UV, (1)H-NMR, (13)C-NMR) as hypolaetin 8-glucoside and the
      new flavonoid sulphate - isoscutellarein 4'-methyl ether 8-glucoside-2''-SO (3)K.

PMID- 17226163
TI  - A New Non-Glycosidic Iridoid and a New Bisiridoid from Argylia radiata1.
AB  - From ARGYLIA RADIATA a non-glycosidic iridoid, the (4a S, 7 S, 7a S)-7-hydroxy-7
      methyl-1,4a,5,6,7,7a-heptahydrocyclopenta[ C]pyran-3(4 H)-one, and a bisiridoid,
      derived from the junction of catalpol and 7-deoxyloganic acid, were isolated.

PMID- 17226164
TI  - Two C, O-Glycosylflavones from Stellaria media1.

PMID- 17226166
TI  - Flavonoids from the Aerial Parts of Geranium robertianum.

PMID- 17226165
TI  - Composition of Agathosma capensis Essential Oil.

PMID- 17226167
TI  - Narciclasine: 1H- and 13C-NMR Data and a New Improved Method of Preparation.

PMID- 17226168
TI  - A Flavone-Glucoside-Cleaving beta-Glucosidase from Chamomilla recutita.

PMID- 17226169
TI  - 6-O-p-Coumaroylcatalpol from Verbascum lychnitis.

PMID- 17226170
TI  - Investigation of the Alkaloid Content of Rauwolfia serpentina Roots from
      Regenerated Plants.
AB  - The indole alkaloid content of RAUWOLFIA SERPENTINA roots from regenerated plants
      (from stem-and root-callus) was compared with the parental stock. Although the
      total alkaloid content seems to be slightly higher in the roots from regenerated
      plants, HPLC-analysis of individual alkaloids indicated that the contents of the
      alkaloids ajmaline ( 1), serpentine ( 2), and reserpine ( 3) are lower than in
      the roots of the parental stock. The glucoalkaloid raucaffricine ( 4) was
      identified as a constituent of all samples, thus providing the first evidence for
      its occurrence in roots of RAUWOLFIA SERPENTINA.

PMID- 17226171
TI  - Isolation and Identification of Homologues of Ajoene and Alliin from Bulb
      Extracts of Allium ursinum.
AB  - From the chloroform extract of ALLIUM URSINUM L. (Liliaceae) bulbs, in addition
      to other sulfur-containing constituents ( E/Z)-4,5,9-trithiadeca-1,6,11-dien-9
      oxide [= methylajoene) and ( E/Z)-4,5,9-trithiaocta-1,6-dien-9-oxide (=
      dimethylajoene) were isolated and identified by NMR and mass spectroscopy. These
      two compounds were also found in A. SATIVUM but in lower amounts. The higher
      contents of the corresponding precursors (+)- S-methyl- L-cysteine sulfoxide
      (MCSO) and methylallyl/allylmethy] thiosulfmate in A. URSINUM water/methanol
      extracts correspond with the higher amounts of ajoene homologues.

PMID- 17226172
TI  - Volatile Constituents of the Rhizome of Homalomena occulta.

PMID- 17226173
TI  - Contribution to the Study of the Essential Oil of Various Cultivars of Juniperus
      sabina.

PMID- 17226174
TI  - Volatile Constituents of Monodora tenuifolia Fruit Oil.

PMID- 17226175
TI  - Diterpenes from Siegesbeckia glabrescens.

PMID- 17226177
TI  - Hentriacontan-7-ol and Hentriacont-7Z-ene from Tamarix dioica1.

PMID- 17226176
TI  - Tetrahydroalstonine from Ophiorrhiza discolor.

PMID- 17226178
TI  - Ursolic Acid from Mitragyna speciosa.

PMID- 17226179
TI  - Incorporation of [1-14C]-Isopentenyl Pyrophosphate into Monoterpenes by a Cell
      Free Homogenate Prepared from Callus Cultures of Chrysanthemum cinerariaefolium.
AB  - Callus culture of CHRYSANTHEMUM CINERARIAEFOLIUM (Trev.) Bocc. (Asteraceae),
      initiated with axillary buds from the plant, have been shown to produce
      chrysanthemyl alcohol and chrysanthemic acid. Incubation of a cell-free
      homogenate from the callus with [1- (14)C]-isopentenyl pyrophosphate demonstrated
      incorporation of radioactivity into chrysanthemyl alcohol and chrysanthemic acid
      as well as products from isopentenyl pyrophosphate isomerase (EC 5.3.3.2;
      isopentenyl diphosphate Delta (3)-Delta (2)-isomerase) and prenyltransferase
      activities (EC 2.5.1.11; allylic-terpene-diphosphate:isopentenyl diphosphate
      terpenoid-allyltransferase).

PMID- 17226180
TI  - Production of Sanguinarine by Chelidonium majus Callus Cultures.
AB  - Tissue callus cultures originating from CHELIDONIUM MAJUS L. seeds were
      established on Gamborg B5, Murashige-Skoog (MS), and Schenk-Hildebrandt (SH)
      media. In all experimental conditions, calli accumulated a complex pattern of
      isoquinoline derivatives. The highest values, both in growth and in sanguinarine
      production, were obtained using SH medium.

PMID- 17226181
TI  - Seasonal Variations of the Flavonoid Content from Ginkgo biloba Leaves.
AB  - An HPLC method for the separation and the quantitative determination of flavonol
      glycosides, acylflavonol glycosides, and biflavones in crude leaf extracts from
      GINKGO BILOBA is described. The results, expressed in percentage of rutine,
      kaempferol P-coumaroyl glucorhamnoside, and bilobetin showed a higher amount of
      acylflavonol glycosides in buds, of flavonol glycosides in spring leaves, and of
      biflavones in autumn leaves.

PMID- 17226182
TI  - Acetylenes and Other Constituents from Artemisia dracunculus.
AB  - The aerial parts of ARTEMISIA DRACUNCULUS afforded several known compounds as
      well as three new acetylenes, two phenylpropane derivatives, two monoterpenes,
      hex-3 Z-en-1-ol and vomifoliol A glucosides. The structures were elucidated by
      spectroscopic methods and a few chemical transformations.

PMID- 17226183
TI  - Two New Glycosides from the Roots of Cynanchum versicolor.
AB  - Two new glycosides named cynanversicoside-A and -B, together with glaucogenin-C
      as the aglycone, were isolated from the Chinese crude drug "Pai-Wei", CYNANCHUM
      VERSICOLOR Bunge (Asclepiadaceae). Their structures were determined on the basis
      of spectral and chemical evidence as glaucogenin-C 3- O-beta- D-cymaropyranosyl
      (1-->4)-alpha- L-diginopyranosyl-(1-->4)-beta- D-thevetopyranoside and
      glaucogenin-C 3- O-beta- D-glucopyranosyl-(1-->4)-beta- D-cymaropyranosyl-(1-->4)
      alpha- L-diginopyranosyl-(1-->4)-beta- D-thevetopyranoside.

PMID- 17226184
TI  - Two New Sesquiterpene Esters from Celastrus glaucophyllus.
AB  - Two new sesquiterpene esters, celaglaupin and celaglausin, have been isolated
      from the root bark of CELASTRUS GLAUCOPHYLLUS. Their structures have been
      elucidated on the basis of two-dimensional NMR (1)H- (1)H COSY, (13)C- (1)H COSY,
      and NOESY) and other spectral (UV, IR, HR-mass, and DEPT) analysis as well as
      chemical methods, respectively.

PMID- 17226185
TI  - Two Novel Protoilludane Norsesquiterpenoid Esters, Armillasin and Armillatin,
      from Armillaria mellea.
AB  - Two novel protoilludane norsesquiterpenoid esters, named armillasin and
      armillatin, have been isolated from the artificially cultured mycelium of
      ARMILLARIA MELLEA (Tricholomataceae). Their structures have been assigned on the
      basis of a detailed study of their spectral data. Their relative configurations
      were established from the nuclear Overhauser effects.

PMID- 17226186
TI  - Auriculatin 4'-O-Glucoside: A New Prenylated Isoflavone Glycoside from Erythrina
      eriotricha1.
AB  - In addition to known compounds, sigmoidin C and 8-(3,3-dimethylallyl)-erythrinin
      C, also called senegalensin, a new isoflavone glycoside designated auriculatin 4'
      O-glucoside was isolated from the chloroform extract of the stem bark of
      ERYTHRINA ERIOTRICHA. Its structure was elucidated as 7,6-(2''',2'''-dimethyl-2 H
      pyrano)-2',5-dihydroxy-8-(3,3-dimethylallyl)-isoflavone 4'- O-beta- D-glucoside
      on the basis of spectroscopic methods and chemical evidence.

PMID- 17226187
TI  - Essential Oils of Achillea ptarmica.
AB  - Using GC and GC/MS, 40 compounds were identified in the essential oils of various
      organs of ACHILLEA PTARMICA. Three ponticaepoxides and (+)-(4 S,6' R)-beta
      sesquiphellandrene could be isolated from the root.

PMID- 17226188
TI  - New cis-Khellactone Esters from Angelica flaccida.

PMID- 17226189
TI  - Tricyclooxyisohumulone: a new autoxidation product of humulone.

PMID- 17226190
TI  - Effect of Near-Ultraviolet Light on Alkaloid Production in Multiple Shoot
      Cultures of Catharanthus roseus.

PMID- 17226191
TI  - Alkaloids of Strychnos usambarensis Stem Bark.

PMID- 17226192
TI  - Phytochemical and Biological Study of Slemmadenia minima.

PMID- 17226193
TI  - Constituents of Persicaria stagnina.

PMID- 17226194
TI  - Triterpenoids from Sarcopoterium spinosum and Sanguisorba minor.

PMID- 17226195
TI  - Caffeic Acid Esters from Urtica dioica and U. urens.

PMID- 17226196
TI  - Review of "liganans, chemical, biological and clinical properties".

PMID- 17226197
TI  - Review of "plant polypheonols. Vegetable tannins revisited".

PMID- 17226199
TI  - Addendum.

PMID- 17226198
TI  - Review of "the healing forest: medicinal and toxic plants of the northwest
      amazonia".

PMID- 17226200
TI  - Anti-hepatitic activity of ginesenoside ro1.
AB  - Ginsenoside Ro, an oleanane-type saponin has been screened for activity in
      experimental models of acute and chronic hepatitis. Ginsenoside Ro (50 and 200
      mg/kg, P.O.) inhibited the increase of serum glutamic oxaloacetic transaminase (s
      GOT) and serum glutamic pyruvic transaminase (s-GPT) levels in D-galactosamine
      (GalN)- and carbon tetrachloride (CCl (4))-induced acute hepatitic rats.
      Ginsenoside Ro inhibited the increase of connective tissue in the liver of CCl
      (4)-induced chronic hepatitic rats. Ginsenoside Ro showed a stronger inhibitory
      effect on the GalN-induced acute hepatitic model than those of the aglycone of
      ginsenoside Ro, oleanolic acid, or glycyrrhizic acid and its aglycone,
      glycyrrhetinic acid.

PMID- 17226201
TI  - Alkaloid Production in Relation to Differentiation in Cell and Tissue Cultures of
      Tabernaemontana pandacaqui.
AB  - Alkaloid production in TABERNAEMONTANA PANDACAQUI cultures is dependent on the
      degree of differentiation. At high levels of production the major alkaloid found
      was 3 S-hydroxyvoacangine. This alkaloid has not previously been isolated from
      any plant. Micropropagation of T. PANDACAQUI was quick and highly efficient.

PMID- 17226202
TI  - Bufadienolides from Urginea maritima sensu strictu.
AB  - Fourteen bufadienolides were isolated from bulbs of hexaploid URGINEA MARITIMA
      (L.) Baker SENSU STRICTU. The compounds were identified by means of FAB-MS, (1)
      NMR and (13)C-NMR studies or comparison with authentic substances. Besides the
      already known proscillaridin A, scillaren A, glucoscillaren A, scilliphaeoside,
      glucoscilliphaeoside, 12- EPI-scilliphaeoside, gamabufotalin-3- O-alpha- L
      rhamnoside, 16beta- O-acetyl-gamabufotalin-3- O-alpha- L-rhamnoside,
      scilliglaucoside, and scillicyanoside, four new bufadienolides were isolated:
      5alpha-4,5-dihydroproscillaridin A, 5alpha-4,5-dihydroglucoscillaren A,
      gamabufotalin-3- O-alpha- L-rhamnosido-beta- D-glucoside, and 19-oxo-5alpha-4,5
      dihydro-proscillaridin A.

PMID- 17226203
TI  - New Indole Alkaloids from Amsonia sinensis.
AB  - Fourteen indole alkaloids, Delta (14)-isoeburnamine ( 1), amsosinine ( 2),
      tabersonine, vincadifformine, lochnericine, tetrahydroalstonine, beta-yohimbine,
      isoeburnamine, minovicinine, picrinine, strictamine, rhazimine, vincanidine, and
      decarbomethoxytetrahydrosecamine, were isolated from AMSONIA SINENSIS. Delta (14)
      isoeburnamine ( 1) and amsosinine ( 2) are new compounds, their structures have
      been established by spectral and chemical methods. A known sterol glycoside,
      daucosterol, has also been obtained. The structures of compounds 1 and 2 were
      finally confirmed by X-ray diffraction of single crystals.

PMID- 17226204
TI  - New Diterpenoids from Euphorbia sieboldiana.
AB  - From the acetone extract of roots of EUPHORBIA SIEBOLDIANA, three known
      diterpenes, ENT-atisane-3beta,16alpha,17-triol ( 1), ingenol ( 4), and
      helioscopinolide A ( 5) as well as two new diterpenes, 3beta- O-acetyl- ENT
      atisane-16alpha,17-diol ( 2), and ingenol-20-palmitate ( 3) were isolated. Their
      structures were elucidated by spectroscopic methods and chemical transformations.

PMID- 17226205
TI  - Two New Oleanane Saponins from Anemone flaccida.
AB  - Two new oleanane saponins, named flaccidoside II and III, were isolated from the
      rhizome of ANEMONE FLACCIDA Fr. Schmidt. On the basis of spectroscopic analysis
      and chemical transformation their structures were elucidated as 3- O-[alpha- L
      rhamnopyranosyl-(1-->2)-beta- D-xylopyranosyl]-oleanolic acid 28- O-[alpha- L
      rhamnopyranosyl-(1-->4)-beta- D-glucopyranosyl-(1-->6)-beta- D-glucopyranoside]
      and 3- O-[beta- D-glucopyranosyl-(1-->2)-beta- D-xylopyranosyl]-oleanolic acid 28
      O-[alpha- L-rhamnopyranosyl-(1-->4)-beta- D-glucopyranosyl-(1-->6)-beta- D
      glucopyranoside].

PMID- 17226206
TI  - Constituents of Knema laurina and Knema tenuinervia ssp. setosa.
AB  - Extraction of the stem bark of KNEMA LAURINA Warb. and KNEMA TENUINERVIA W. J. J.
      O. de Wilde ssp. SETOSA de Wilde furnished 3-(12-phenyl-8 Z-dodecenyl)-phenol and
      3-(8 Z-pentadecenyl)-phenol together with 8-hydroxy-6-methoxy-3- N
      pentylisocoumarin, respectively. 2-Carboxy-3-(12-phenyldodecyl)-phenol) and 2,4
      dihydroxy-6-(10-phenyldecyl)-acetophenone were common to both extracts.

PMID- 17226207
TI  - Pyrrolizidine Alkaloids from Ageratum conyzoides.

PMID- 17226208
TI  - Minor Alkaloids of Lupinus albus: 13alpha-Hydroxymultiflorine and 13alpha-Hydroxy
      5-dehydromultiflorine1.

PMID- 17226209
TI  - Isoquinoline Alkaloids from Cardiopetalum calophyllum.

PMID- 17226210
TI  - Essential Oil of Thapsia garganica.

PMID- 17226212
TI  - Alkaloids of Anatolian Thalictrum minus var. majus.

PMID- 17226211
TI  - The Essential Oil of Cymbopogon giganteus.

PMID- 17226213
TI  - Abietane-Type Diterpene Quinones from Salvia nipponica.

PMID- 17226214
TI  - Phenolic Constituents of Rhodiola coccinea, a Tibetan Folk Medicine1.

PMID- 17226215
TI  - New Constituents of Astragalus mongholicus.

PMID- 17226216
TI  - The metabolism of a natural product: lessons learned from cyanogenic glycosides.
AB  - The biosynthesis, compartmentation, and catabolism of cyanogenic glycosides are
      discussed for the cases of some selected examples. These include amygdalin
      (occurring widely in the Rosaceae), the aliphatic cyanogens linamarin and
      lotaustralin (widely occurring, especially in the Leguminosae), and dhurrin
      together with its epimer taxiphyllin (occurring in the genus SORGHUM).
      Mechanistic studies including tracer experiments are described in detail. Unusual
      and even unique metabolites of amino acids have been identified as intermediates
      in these biosynthetic processes.

PMID- 17226217
TI  - Metabolism of monoterpenes in mint (mentha) species.
AB  - Commercial mint ( MENTHA) species produce either C3-oxygenated or C6-oxygenated P
      menthane monoterpene as the major essential oil components. The biosynthetic
      origin of both of these monoterpene families from the common precursor (-)
      limonene is described. The metabolic turnover of monoterpenes occurs during late
      stages of plant development, and the pathway for the transport and catabolism of
      (-)-menthone in peppermint is reviewed as a model for this general process. The
      developmental regulation of monoterpene metabolism is briefly outlined.

PMID- 17226218
TI  - Coumarins and other phenylpropanoid compounds in the defense response of plant
      cells.
AB  - Cultured cells of the Apiaceae, e. g. PETROSELINUM CRISPUM and AMMI MAJUS,
      produce large quantities of coumarin phytoalexins upon treatment with fungal
      elicitors and concomitantly reinforce their cell walls by ferulic ester
      incorporation. In these reactions, the cells mimic the disease resistance
      response commonly expressed in plants following infection by phytopathogenic
      fungi. Both coumarins and ferulic esters are derived from the general
      phenylpropanoid pathway. The elicited Apiaceae cell cultures have therefore
      served as model systems for the investigation of the biosynthetic and regulatory
      mechanisms involved in phenylpropanoid accumulation. The results of these studies
      suggest an unconventional pathway for umbelliferone biosynthesis and demonstrate
      both the transcriptional and post-transcriptional control of a novel pathway to
      feruloyl-CoA. They underline the enormous contribution of such model systems to
      the present knowledge on regulatory patterns and DNA coding in secondary
      metabolism.

PMID- 17226219
TI  - Transport and secretion of natural products in plant cell cultures.
AB  - Using the example of berberine in cell cultures of THALICTRUM and BERBERIS
      species, the transport and secretion of natural products in plant cell cultures
      is reviewed. Topics discussed are the subcellular localization of berberine
      biosynthesis, transport of berberine to vacuoles, extracellular release of
      berberine, mechanism of berberine secretion, uptake and transport of exogenous
      berberine, and the release of berberine by immobilized cells.

PMID- 17226220
TI  - Strategies for the genetic manipulation of alkaloid-producing pathways in plants.
AB  - Increasingly, as a result of recent biochemical work, there exists a realistic
      possibility of taking a molecular genetic approach to the manipulation of
      alkaloid-producing pathways in plant tissue cultures. In the pathways forming
      indole alkaloids in CATHARANTHUS ROSEUS, tropane alkaloids in DATURA and
      HYOSCYAMUS species, and nicotine in NICOTIANA species, recent studies have
      identified a number of key enzymes and at least some of the factors that regulate
      their levels of activity. Such knowledge contributes the basis upon which it has
      become feasible to design a strategy by which the flux in these pathways may be
      enhanced at the genomic level. This review presents a summary of the state-of-the
      art pertaining to these pathways and discusses the strategy to be adopted for a
      molecular approach to their manipulation, together with some of the pitfalls that
      may arise when trying to alter their natural regulation.

PMID- 17226221
TI  - The genetic and biochemical basis of polyketide metabolism in microorganisms and
      its role in drug discovery and development.
AB  - The possibilities for the design of new drug screening and development strategies
      directed to a specific objective on the basis of genetic engineering of
      microorganisms is discussed from two points of view. Firstly, results of work on
      genetic hybrids of STREPTOMYCES species for the production of new metabolites
      such as mederrhodin (1) and aloespanoarin II (4) are described. Secondly, the
      enhanced production of known metabolites such as tetracenomycin A (2) (11) and
      tetracenomycin C (9) by recombinant STREPTOMYCES species is considered.
      Mechanistic aspects of polyketide metabolism are included.

PMID- 17226222
TI  - Molecular mechanisms of the a-factor-dependent control of secondary metabolism in
      streptomyces.
AB  - A-factor, 2-isocapryloyl-(3 R)-hydroxymethyl-gamma-butyrolactone, is a microbial
      hormone controlling secondary metabolism and morphogenesis of STREPTOMYCES
      GRISEUS. The A-factor-receptor protein present in the cytoplasm is a repressor
      type regulator; it plays a role in repressing streptomycin production and
      sporulation while the binding of A-factor to the receptor protein releases its
      repression. Thus, secondary metabolism and sporulation of S. GRISEUS involve a
      step of hormonal regulation by A-factor. The AFSR gene codes for a global
      regulatory protein of 993 amino acids controlling positively secondary metabolic
      formation in STREPTOMYCES COELICOLOR A3(2), probably at the transcriptional
      level. This protein comprises two domains, i.e., an ATP-binding domain at its NH
      (2)-terminal portion and a DNA-binding domain with a helix-turn-helix motif at
      its COOH-terminal portion. The AfsR protein is found to be phosphorylated. It is
      assumed that the extent of phosphorylation-dephosphorylation of the AfsR protein
      modulates the expression of genes responsible for secondary metabolic formation.

PMID- 17226223
TI  - Modern phytotherapy and its uses in gastrointestinal conditions.
AB  - A discussion of the historical background, development, and legal and
      philosophical aspects of phytotherapy as well as suggestions for its scientific
      basis is presented. Applications of phytotherapy for various gastrointestinal
      conditions are discussed for the examples of three remedies. The first example is
      liquorice root, its active principle carbenoxolone, and the drugs Biogastrone and
      Caved-S for the treatment of gastic, peptic and duodenal ulcers; the second
      example is the fruits of the milk thistle, its active principles silymarin and
      silybinin as well as the drug Legalon for the treatment of liver diseases. The
      third example concerns the use of laxatives of plant origin such as plantain
      seeds and the drugs Agiocur and Agiolax. The review concludes with suggestions
      for the future course of phytotherapeutic research.

PMID- 17226224
TI  - Antiprotozoal agents from plant sources.
AB  - Protozoa are responsible for a number of serious tropical diseases including
      amoebiasis, leishmaniasis, malaria, and trypanosomiasis. New drugs are required
      for the treatment of these diseases and the potential of plants to produce new
      clinical agents is discussed.

PMID- 17226225
TI  - Cannabinoids: the separation of central from peripheral effects on a structural
      basis.
AB  - A brief history of the therapeutic uses and legal problems of cannabis as well as
      the component cannabinoids is given. This is followed by a discussion of drug
      development from Delta (1)-tetrahydrocannabinol and its synthetic analogues. The
      controversy of whether the pharmacological effects are of central or peripheral
      origin is included. Then, the potentials for the development of new drugs based
      on the cannabinoid structure for the treatment of pain, inflammation, and related
      conditions are outlined. It is concluded that the central activity of
      cannabinoids is confirmed and that the presence of a C-5 hydroxy group confers
      potent peripheral activity.

PMID- 17226226
TI  - Old and new natural products as the source of modern antithrombotic drugs.
AB  - Natural compounds have been the first historical source of antithrombotic
      compounds (heparin, vitamin K antagonists, streptokinase, urokinase); molecules
      extracted from plants or animals still provide some of the most original and
      promising approaches for the discovery of new drugs in this class. In this
      review, we will briefly describe three examples of current research trends that
      could lead to the development of new antithrombotic drugs of natural origin.
      Flavonoids have been shown to be inhibitors of cyclic nucleotide
      phosphodiesterase; this enzymatic activity is one of the main mechanisms of
      inhibition of aggregation of blood platelets by flavonoids. Some of these
      compounds could represent templates for the development of new inhibitors of
      platelet activation. Garlic ( ALLIUM SATIVUM) has been shown to inhibit platelet
      aggregation IN VIVO and IN VITRO; a number of active principles has now been
      identified and their mechanisms of action are currently being explored. An
      ancient remedy, the medicinal leech ( HIRUDO MEDICINALIS), has been found to
      contain several potent anticoagulant proteins. Among them, hirudin, a polypeptide
      of 65 amino acids, has been identified as one of the most potent inhibitors of
      thrombin. The production of sufficient amounts of hirudin through molecular
      biology techniques has now allowed the performance of clinical trials. These
      three examples show that careful consideration of biochemical,
      ethnopharmacological, or toxicological properties of natural products can still
      constitute a valuable basis for the development of new drugs.

PMID- 17226227
TI  - Endogenous Alkaloids in Man - Synthesis, Analytics, in vivo Identification, and
      Medicinal Importance*,1.
AB  - The IN VITRO and IN VIVO condensation of endogenous (or administered) reactive
      amines and carbonyl compounds is reported, leading to alkaloid-type heterocycles.
      The spectrum of the presented "mammalian alkaloids" ranges from isoquinoline
      derivatives, via beta-carbolines, through to thiazolidines, arising from vitamin
      B (6), chloral, and glyoxylic acid, respectively. Formation of these compounds
      may occur accidentally, but might also be induced intentionally, as a therapy for
      metabolic diseases.

PMID- 17226228
TI  - beta-Carbolines and Tetrahydroisoquinolines: Detection and Function in Mammals.
AB  - beta-Carbolines occur in man and rat. The concentration in various tissues is
      about 100 to 1000 times lower than that of classical neurotransmitters.
      Administration of beta-carbolines in animals induces overlapping but not
      identical activity profiles. The molecular modes of action differ. For example,
      harman (1-methyl-beta-carboline) acts as an endogenous inhibitor of monoamine
      oxidase [E.C. 1.4.3.4.], subtype A, whereas norharman (beta-carboline) probably
      acts by stimulation of a specific beta-carboline receptor which is different from
      the benzodiazepine-GABA receptor complex. There is substantial evidence that
      tetrahydroisoquinolines occur under physiological conditions as well. Whether
      tetrahydropapaveroline serves as a precursor of morphinanes in mammals, as has
      been found in opium poppies, remains to be elucidated.

PMID- 17226229
TI  - Mammalian Alkaloids: Conversions of Tetrahydroisoquinoline-1-carboxylic Acids
      Derived from Dopamine*.
AB  - Racemic and optically active mammalian 6,7-dihydroxy-1,2,3,4
      tetrahydroisoquinoline-1-carboxylic acids derived from dopamine, and
      quinonemethides obtained from them by oxidative decarboxylation at physiological
      pH 7-9, are methylated by S-adenosyl- L-methionine in the presence of catechol- O
      methyl-transferase IN VITRO exclusively at the OH-group at C-7. It can,
      therefore, be stated that these acids are unlikely intermediates in the
      biosynthesis of isoquinolines en route to morphine. Enantiospecific and
      regioselective O-methylations observed with ( S)- and ( R)-norcoclaurines,
      leading in the ( S)-series predominantly to compounds methylated at the hydroxy
      group at C-6, and in the ( R)-series to isomers methylated at the hydroxy group
      at C-7, respectively, are in full accord with similar reactions occurring in the
      plant biosynthesis of morphine. Since the same methylation pattern is ascertained
      in reactions catalyzed by mammalian enzymes, it is suggested that mammals might
      be capable of synthesizing morphine from the same isoquinoline precursors.

PMID- 17226434
TI  - [Experience with laryngotracheal reconstruction in subglottic stenosis in a 30
      years time period].
AB  - BACKGROUND: Severe subglottic stenosis is a difficult condition to manage. It can
      be treated by laryngotracheal reconstruction or cricotracheal resection. PATIENTS
      AND METHODS: In this retrospective study the experiences for treatment of
      isolated subglottic stenosis in 37 patients (age: 3-78 years; stenosis grading:
      20 x grade II, 13 x grade III, and 4 x grade IV) by laryngotracheal
      reconstruction in a 30-years experience are presented. RESULTS: In 33 out of 37
      patients (89.2 %) a sufficient subglottic patency (postoperative endoscopic
      finding: stenosis less than 30 %) was achieved by laryngotracheal reconstruction.
      However, 5 patients of this series had required revision of laryngotracheal
      recontruction and in 22 patients endoscopic removal of granulation tissue had
      been performed. Sufficient widening of the subglottic space had been possible in
      all grade II stenosis (20/20), in 11 out of 13 patients with grade III stenosis,
      and in 3 out of 4 patients with grade IV stenosis. In one child an accidental
      decannulation occurred and due to asphyxia an apallic syndrome developed.
      CONCLUSIONS: Even through laryngotracheal reconstruction is a demanding surgical
      technique requiring great experience it is an effective option for treatment of
      subglottic stenosis less than 90 %. For severe subglottic stenosis (> 90 %)
      treatment by laryngotracheal reconstruction is possible and should be considered
      if mobilisation of the trachea by scar tissue is suited to be worse or to
      extended cricotracheal stenosis is present, both being not good candidates for
      cricotracheal resection.

PMID- 17226436
TI  - [A new model for training in tympanoplasty].
AB  - BACKGROUND: Functional simulation of middle ear reconstruction is a valuable
      tools for training in otosurgery. We introduce a new experimental model which
      provides a direct acoustic feedback of the functional quality of ossicular chain
      reconstruction. METHOD: In this model the tympanic membrane and the ossicular
      chain have to be reconstructed for proper sound transmission to an artificial
      inner ear receptor. The received signal is converted into acoustic information
      and consecutively provided via headphone. RESULTS: Any changes in the
      reconstruction (e. g. tilting the prosthesis) can be experienced online and
      immediately optimized by the surgeon or a trainee. CONCLUSION: The experimental
      model can be used for demonstration and training in otosurgery. This model is
      also suitable for comparing measurements of transfer functions in a calibrated
      version and can be applied to development and critical evaluation of middle ear
      prostheses.

PMID- 17226437
TI  - Transformation of Progesterone by Traemetes hispida.
AB  - TRAEMETES HISPIDA was found to convert progesterone into a mixture of various
      products. Five products were isolated in sufficient amounts by HPLC analysis for
      structural identification and characterization. Three products were found to have
      two hydroxy moieties on axial and equatorial positions at 7beta,15beta, 6beta,
      11alpha, and 11alpha, 15beta sites. The other two products had an extra 17alpha
      hydroxy on the above dihydroxy derivatives to give trihydroxyprogesterone. The
      hydroxylating steps caused by this strain were greatly influenced by the 17beta
      side chain, especially by the C-20 moiety in the steroidal skeleton.

PMID- 17226435
TI  - [Is orbital exenteration indicated for extensive primary mucosal melanomas of the
      sinunasal system?].
AB  - Primary mucosal melanomas are most frequently localized in the sinunasal system.
      Orbital involvement must be excluded in the mostly advanced tumor stage. The aim
      of our study was to find possible indications for orbital exenteration in the T3
      4 sinunasal tumor stage. We evaluated 14 treatment courses at our department from
      1988 to 2004. The analysis disclosed orbital involvement in 43 % of the patients.
      The one patient submitted to orbital exenteration had a survival of only 28
      months, which was not relevantly longer than in the other 9 patients with a T3-4
      tumor stage (median survival of 27 months) or to the two patients with purely
      palliative treatment (survival of 10 and 21 months). We conclude that, due to the
      high generalized metastasis rate, radical surgical procedures can only prolong
      survival in individual cases of advanced-stage sinunasal tumors. Orbital
      decompression should be considered with reference to the quality of life.

PMID- 17226438
TI  - Shoot Tip Culture of Arnica montana for Micropropagation.
AB  - Multiple shoots were regenerated from shoot tips of ARNICA MONTANA on MS and B5
      media supplemented with BA (1 mg/l) and NAA (0.1 mg/l). Sections of 1-2 mm in
      length cultured from IN VITRO germinated seedlings regenerated 7.7 (mean) shoots
      on the MS medium, whereas sections cultured from greenhouse plants regenerated
      9.0 (mean) shoots on the B5 medium within 6 weeks. Subsequent subcultures of
      shoots on the same media but without NAA resulted in similar or lower
      multiplication rates (1.6 to 3.1 in 3 weeks). Shoot development was promoted,
      whereas shoot initiation was simultaneously inhibited by the addition of
      activated charcoal to the media. Rooting was induced by culturing shoots from
      seedling as well as from greenhouse plant shoot tips on MS or B5 medium
      supplemented with NAA. The plantlets were transplanted into soil and grown
      successfully under greenhouse and field conditions.

PMID- 17226439
TI  - Variation in Growth and Secondary Phenolics Among Field-Cultivated Clones of
      Salix myrsinifolia.
AB  - Nine S. MYRSINIFOLIA clones were studied for secondary phenolics and phytomass
      production in an old, unfertilized hayfield after the second growing season. S.
      MYRSINIFOLIA is one of the most promising willow species for the production of
      herbal drug material. Its salicylate content is moderately high in all parts of
      the shoot. The leaf and stem phytomass varied significantly among clones, but
      more than 70% of the total variation could be explained by within-clonal
      phytomass variation. Similarly, the accumulation of salicin, salicortin,
      chlorogenic acid (+)-catechin, proanthocyanidins, and unknowns varied
      significantly according to source (tissue, individual, or clone), and in most
      cases the environmental (within-clonal) variation was nearly as high as the
      genetic variation (between-clones). In the selection of the best clones for the
      production of herbal drug material three main factors should be taken account:
      costs of cultivation, costs for transportation, and costs for production of
      extracts. A high phytomass clone may be a low-quality clone as far as salicylates
      are concerned.

PMID- 17226440
TI  - Inheritance of Biomass Yield and Tropane Alkaloid Content in Hyoscyamus muticus.
AB  - The nature of gene action for biomass yield and tropane alkaloid content was
      ascertained through diallel analysis in Egyptian henbane, HYOSCYAMUS MUTICUS L.
      Dominance variation was preponderant over additive genetic variance, dominance
      being in the overdominance range for both traits. On an overall basis, recessive
      alleles had a positive (i.e. increasing) effect on both the characters. However,
      the positive or negative effects of recessive or dominant alleles were genotype
      specific. Hence, transgressive breeding was suggested for isolating segregants
      with dominant alleles for herb yield and with recessives for alkaloid content so
      as to achieve overall high yields of tropane alkaloid per unit area.

PMID- 17226441
TI  - Phenylethylamine and piperidine alkaloids in aloe species.
AB  - Of the approximately 300 species of ALOE (Liliaceae) native to Africa and Arabia,
      leaf extracts of 224 species have been examined chromatographically for alkaloids
      using ninhydrin, Dragendorff's reagent, nitroprusside, and iodoplatinate as
      revealing agents. From these, 48 (21%) species contained compounds giving a
      strong colorimetric reaction with at least one of these reagents. Tyramine
      derivatives were identified in 18 species and piperidine derivatives in a further
      6 species. The other coloured zones remain unidentified but often appeared to
      represent common amino acids. Some taxonomic correlations are suggested. The
      presence of the toxic hemlock alkaloids in aloes readily available for potential
      medicinal use by local inhabitants sounds a note of caution against the
      unthinking use of these otherwise useful plants.

PMID- 17226442
TI  - Microdontin A and B: Two New Aloin Derivatives from Aloe microdonta.
AB  - The leaf juice of ALOE MICRODONTA Chiov. is used in Somali traditional medicine
      as a remedy for jaundice and for topical treatment of skin diseases. Mucilage was
      precipitated from the fresh juice by addition of ethanol and the supernatant
      chromatographed on Amberlite XAD-2 to yield a fraction containing anthraquinone
      derivatives. Flash chromatography on silica gel followed by preparative TLC
      yielded aloin A and a new compound. Spectral data (mass, (1)H- and (13)C-NMR)
      identified this compound as a mixture of aloin A and B where the glucose of both
      compounds is esterified with 4-hydroxycinnamic acid at the 6'-position. The two
      compounds were denoted as microdontin A and B, respectively.

PMID- 17226443
TI  - Comparative Investigations of the Cardenolide Pattern of Four Varieties of
      Digitalis subalpina Br.-Bl*.
AB  - No remarkable differences in the cardenolide pattern of the four varieties of
      DIGITALIS SUBALPINA could be found. Subalpinoside (Oleandrigenin
      glucodigitoxoside) is the main cardiac glycoside in all varieties.

PMID- 17226444
TI  - Volatile Constituents of Achillea grandifolia.
AB  - Volatile constituents of ACHILLEA GRANDIFOLIA Friv. growing wild in Greece were
      studied by means of GC and GC-EIMS. Sixty constituents were identified. The main
      components were camphor, alpha- and beta-thujone, and 1,8-cineole. Twenty-six
      constituents have not been previously reported in the essential oils of the genus
      Achillea.

PMID- 17226445
TI  - Alkaloidal Constituents of Corydalis stewartii.

PMID- 17226447
TI  - Cepharadione A from Piper methysticum.

PMID- 17226446
TI  - Iridoid Glucosides from the Fruits of Lonicera morrowii.

PMID- 17226448
TI  - Absolute Structure of Kiwiionoside as a Precursor of Loliolide and Actinidiolide,
      from Actinidia chinensis.

PMID- 17226449
TI  - Sesquiterpene Lactones from Picris hieracioides subsp. hieracioides.

PMID- 17226450
TI  - Erratum.

PMID- 17226451
TI  - Letters to the editor.

PMID- 17226452
TI  - The influence of tryptophan and tryptamine feeding and light on alkaloid
      biosynthesis in cinchona seedlings.
AB  - It has previously been shown that, at the onset of germination of CINCHONA seeds,
      transient increases in both the tryptophan level and tryptophan decarboxylase
      (TDC) activity occur. Subsequently, in the seedlings the levels of the TDC
      product tryptamine and its derived alkaloids increase. We investigated whether
      this process can be influenced by external tryptophan or tryptamine feeding.
      Besides, the possible role of light in alkaloid biosynthesis was studied by
      monitoring this process in etiolated seedlings. Tryptophan feeding slightly
      raised the TDC activity in the seedlings, but alkaloid production remained
      unaltered. During tryptamine feeding, the transient increases in tryptophan level
      and TDC activity were still observed, and also here, alkaloid production remained
      unaltered. Finally, in etiolated seedlings the alkaloid biosynthetic pathway
      proceeded normally. Thus, in germinating CINCHONA seedlings alkaloid production
      is not susceptible to tryptophan or tryptamine feeding and independent of light.

PMID- 17226453
TI  - Localization of the biosynthesis and accumulation of monoterpenoids in glandular
      trichomes of thyme.
AB  - Quantitative analyses of the essential oils in intact glandular trichomes
      isolated from thyme cotyledons by the use of an adhesive tape and a glass
      capillary tube showed that the content of thymol per cotyledon was approximately
      equal to the sum total of thymol in peltate glandular trichomes (PGTs) and
      capitate glandular trichomes (CGTs). The amounts of thymol and gamma-terpinene in
      PGTs increased with time until 9 days after germination, when these monoterpenes
      were exclusively found in PGTs. The radioactivity of [U- (14)C]-sucrose
      administered to cotyledonal segments was incorporated into gamma-terpinene and
      thymol most actively by the peripheral part abundant in PGTs, whereas the
      incorporation was markedly decreased by a partial removal of PGTs from
      cotyledons. The cell-free extract of isolated PGTs was capable of cyclizing [
      (14)C]-geranyl pyrophosphate into gamma-terpinene, but this enzymatic reaction
      failed when PGTs were removed from cotyledons. These results indicate that the
      biosynthesis and accumulation of monoterpenes in thyme seedlings take place
      primarily in PGTs.

PMID- 17226454
TI  - NMR-Assignments of N-Acylaporphine Alkaloids from Tinospora crispa.
AB  - N-Formylannonaine ( 1), N-formylnornuciferine ( 2) and N-acetylnornuciferin ( 3),
      have been isolated from stems of TINOSPORA CRISPA (Menispermaceae), and their NMR
      spectra have been fully assigned by 2D-NMR experiments. This is the first
      reported occurrence of N-formyl- and N-acetylaporphines from the genus TINOSPORA.

PMID- 17226455
TI  - Genetic Control of Peltate Glandular Trichome Formation in Perilla frutescens.
AB  - The inheritance of peltate glandular trichome (PGT) formation in PERILLA
      FRUTESCENS leaves was investigated by crossing a normal strain with a variant
      strain with sparse PGT formation. The F (1) and F (2) data suggested that the
      sparse trichome is a dominant character that is controlled by a major gene and a
      few modifying genes which specifically inhibit the development of trichomes of
      the peltate type. Tracer experiments using [ (14)C]-sucrose showed that the
      quantity of essential oil components synthesized in the leaf was positively
      correlated with the number of PGTs, suggesting that the PGT is the main site for
      the biosynthesis of essential oil.

PMID- 17226456
TI  - Canthin-6-one and beta-Carboline Alkaloids from Aerva lanata.
AB  - From the herb of AERVA LANATA six alkaloids were isolated. Canthin-6-one ( 1) and
      beta-carboline-1-propionic acid ( 5) have been found previosly while 10-methoxy
      canthin-6-one ( 2), 10-hydroxy-canthin-6-one ( 3),10- O-beta- D
      glucopyranosyloxycanthin-6-one ( 4), 6-methoxy-beta-carboline-1-propionic acid (
      6) are new alkaloids. Their structures were determined by means of spectoscopic
      analysis and chemical transformations.

PMID- 17226457
TI  - Salvianolic Acids D and E: Two New Depsides from Salvia miltiorrhiza.
AB  - Four water-soluble constituents, salvianolic acids D, E, ethyl lithospermate, and
      isoferulic acid were isolated from SALVIA MILTIORRHIZA. Salvianolic acids D and E
      are new depsides. Their chemical structures were determined by chemical and
      spectral analysis. The structure of salvianolic acid D was finally confirmed by
      comparison with a synthetic product.

PMID- 17226458
TI  - Studies on the Constituents of Adelostemma gracillimum.
AB  - The glycone portion of the glycoside of ADELOSTEMMA GRACILLIMUM Hook. f.
      (Asclepiadaceae) was investigated. Three known polyoxypregnane ester-type
      aglycones, penupogenin ( 1) (1, 2), kidjoranine ( 2) (1, 3), and gagamine ( 3)
      (4, 5), and one new compound named gracigenin ( 4) were isolated and their
      structures were characterized on the basis of spectroscopic evidence, and that of
      ( 4) was determined by X-ray crystallography. It was found to possess an
      unprecedented 8,14- SECO-polyoxypregnane ester-type skeleton, and 4 is the first
      compound with this C (21)-steroid type skeleton to be found in nature.

PMID- 17226459
TI  - Chemical Constituents of the Lichen Ramalina hierrensis.
AB  - The following compounds have been isolated from the lichen RAMALINA HIERRENSIS,
      collected on savin, and endemic to the Canary Islands: ursolic acid, iso
      arborinol acetate, beta-sitosterol, ergosterol peroxide, cerevisterol, (-)
      sandaracopimaric acid, parietin, (+)-usnic acid, (+)-iso-usnic acid, divaricatic
      acid, atranorin, stictic acid, gangaleodin, variolaric acid, montagnetol, and
      hierridin. The structures of all compounds were elucidated by physical, spectral,
      and chemical methods.

PMID- 17226460
TI  - Composition of the Essential Oil of Cymbopogon travancorensis.
AB  - The chemical composition of the essential oil of CYMBOPOGON TRAVANCORENSIS Bor.
      (Poaceae) was investigated by capillary GC and GC-MS. Thirty-five compounds were
      identified. The oil contains mono- and sesquiterpene hydrocarbons (39.60%),
      oxygenated terpenes (30.45%), and phenyl propanoids (22.04%). The main
      constituents of the oil are camphene (11.86%), limonene (18.07%), borneol
      (9.71%), elemicin (17.22%), and elemol (11.21%).

PMID- 17226461
TI  - Glycyrrhetol and beta-Peltoboykinolic Acid from Adenocalymma alliaceum.

PMID- 17226462
TI  - Tormentic Acid and 2alpha-Hydroxyursolic Acid from Arnebia euchroma.

PMID- 17226463
TI  - Limonoids of Fagaropsis glabra.

PMID- 17226464
TI  - Cardenolide and Neutral Lipid Biosynthesis from Malonate in Digitalis lanata.
AB  - DIGITALIS LANATA plants were grown on water culture in a controlled environment
      and in the young, growing leaves free sterols (0.335 micromol/g FW),
      triacylglycerols (0.97 micromol/g FW) and cardenolides (1.82 micromol/g FW) were
      the major apolar and polar lipids. The cardenolide-containing fraction from these
      tissues was separated into 26 cardenolides by HPLC. The 5 major components
      (accounting for 60 % of the occurring glycosides) lanatosides A and C,
      acetyldigoxin, acetyldigitoxin, and glucoevatromonoside were identified by FABMS.
      Incorporation experiments with [2- (14)C]-acetate, [2- (14)C]-malonate, [2-
      (14)C]-mevalonate, and [U- (14)C]-sucrose (absorbed by excised, young, growing
      leaves) showed the labelling of all the occurring cardenolides after a 3 day
      incorporation period (as judged by HPLC). Comparing the simultaneous synthesis of
      labelled sterols and triacylglycerols, malonate could be considered as the most
      effective precursor in cardenolide synthesis, reaching an incorporation value of
      4.1 % in a 4 day incorporation period. A time-course experiment revealed a
      temporary accumulation of (14)C in glucoevatromonoside, which may play a role as
      an intermediate in cardenolide production of DIGITALIS LANATA.

PMID- 17226465
TI  - Search for Factors Related to the Indole Alkaloid Production in Cell Suspension
      Cultures of Tabernaemontana divaricata.
AB  - Three strains derived from one cell line of a suspension culture of
      TABERNAEMONTANA DIVARICATA were obtained by subculturing on three different
      media: (i) Strain A: normal MS-medium (1), (ii) Strain S: medium in which the
      carbon source was starch instead of sucrose, and (iii) Strain N: medium in which
      the ammonium/nitrate ratio was changed from 1: 2 to 1:1. The alkaloid contents of
      all three strains were compared at each subculture for nearly one year. Strain N
      showed after its initiation a gradually increasing alkaloid production up to
      levels of about 500 microg/gDW. Strain A (on the original medium) showed a
      stable, but low alkaloid production (+/- 20 microg/gDW) while strain S turned
      into a non-producing line. The dissimilation curves, morphology, intracellular
      carbohydrates, and free amino acid pools of all three strains were determined.
      Strain N showed the highest biomass, the least dissimilation, most plastids, most
      intracellular carbohydrates, and high levels of arginine and glutamine, while
      strain S showed the lowest biomass, most dissimilation, no plastids, little
      intracellular carbohydrates, and high levels of arginine, phenylalanine, and
      tyrosine. The observed differences are discussed and evidence is provided that
      the differences are not caused by genetic instability.

PMID- 17226466
TI  - Structure revision of 4-hydroxyaloin: 10-hydroxyaloins a and B as main in vitro
      oxidation products of the diastereomeric aloins1.
AB  - A reinvestigation of the anthrone derivative 4-hydroxyaloin as main product of
      the mild IN VITRO-oxidation of aloin has led to the revision of the proposed
      structure as the aloin-analogous oxanthrone derivative, the new 10-hydroxyaloin,
      which was prepared from aloin by an improved procedure in ammonia at pH 9. 10
      Hydroxyaloin was separated into its C10-diastereomers A and B by analytical and
      preparative chromatographic methods. Their structures were elucidated by
      spectroscopic methods (FAB-MS; (1)H/ (13)C-NMR; CD), which show that 10
      hydroxyaloin A is the 10 R,1' R compound and that 10-hydroxyaloin B has the 10
      S,1' R-configuration.

PMID- 17226467
TI  - New Lignan Glucosides from Stemmadenia minima*.
AB  - Reinvestigation of the polar fractions from the stem bark of STEMMADENIA MINIMA
      A. Gentry (Apocynaceae) afforded two known and four new lignan glucosides. Their
      structures were deduced by spectroscopic and chemical methods.

PMID- 17226468
TI  - The Essential Oil of Sphacele chamaedryoides.

PMID- 17226469
TI  - Light inhibits the formation of capsaicin from capsicum callus.

PMID- 17226470
TI  - Pyrrolizidine Alkaloids from the Seeds of Crotalaria sessiliflora.

PMID- 17226471
TI  - Flavonoids from Carthamus tinctorius Flowers.

PMID- 17226472
TI  - A Furanocoumarin from Angelica archangelica.

PMID- 17226473
TI  - Elaeocarpidine, a Naturally Occurring Racemate, from Tarenna vanprukii.

PMID- 17226474
TI  - Adhyperforin: A Homologue of Hyperforin from Hypericum perforatum.

PMID- 17226476
TI  - Isolation and Characterisation of Sulphur Compounds from Tulbaghia violacea.

PMID- 17226475
TI  - Isoachifolidiene, a Precursor of Guaianolide Peroxides from Achillea
      millefolium1.

PMID- 17226477
TI  - Canthin-6-one and beta-Carboline Alkaloids from Hannoa chlorantha Root Bark.

PMID- 17226478
TI  - Alkaloids from Cybistetes longifolia.

PMID- 17226479
TI  - Cathin-6-one from the Root Bark of Phellodendron chinense.

PMID- 17226480
TI  - Artemisinin G: A Sesquiterpene from Artemisia annua.

PMID- 17226481
TI  - Production of Forskolin in in vitro Cultures of Coleus forskohlii.
AB  - Shoot tip culture, root organ suspension, and callus culture producing roots were
      established from shoot tip, root tip, and hypocotyl segments, respectively, on
      Murashige and Skoog's and White's basal media with or without growth regulators.
      Forskolin was identified by TLC and HPLC in 60 days old shoot differentiating
      culture, 30 days old micropropagated plants, and root organ suspension but not in
      rhizogenic callus. Shoot differentiating culture established in the presence or
      absence of BAP revealed more or less similar amounts of forskolin as that of the
      micropropagated plants. Root organ suspension showed traces of forskolin
      production.

PMID- 17226482
TI  - Production of Forskolin by Axenic Coleus forskohlii Roots Cultivated in Shake
      Flasks and 20-l Glass Jar Bioreactors*.
AB  - Root cultures of COLEUS FORSKOHLII Briq. were initiated from primary callus or
      IBA-treated suspension cultures and maintained on Gamborg's B5 medium containing
      1 mg/l IBA. Transformed root cultures were established by infecting surface
      sterilized leaves with AGROBACTERIUM RHIZOGENES strain 15834. Transformation was
      confirmed by mannopine detection. These cultures displayed the typical
      characteristics of hairy root cultures, with the sole exceptions of slow growth
      in hormone-free medium and accelerated growth on medium containing phytohormones.
      All root cultures examined formed forskolin and its derivatives in amounts
      ranging from 500 to 1300 mg/kg dry weight, corresponding to about 4 to 5 mg/l.
      During cultivation roots could be cut into small pieces without affecting growth
      and forskolin production. Scale-ups of the cultivation procedure were performed
      in 20-l glass jars with a working volume of 10 to 13l. Forskolin production in
      bioreactors was better than in shake flasks. Levels of almost 14 mg/l could be
      reached after 21 d of cultivation. As in the shake flask experiments cutting the
      roots did not affect growth or productivity in a negative way.

PMID- 17226483
TI  - Characterization of the formation of allicin and other thiosulfinates from
      garlic.
AB  - The effects of pH, neutralization after acidification, time, and temperature on
      the yield of dialkyl thiosulfinates released from garlic powder and garlic cloves
      were determined. All dipropenyl thiosulfinates (allicin, 1-propenyl allyl, and
      allyl 1-propenyl) were formed at an optimum pH of 4.5-5.0. The methyl propenyl
      thiosulfinates (allyl methyl + methyl allyl and 1-propenyl methyl + methyl 1
      propenyl) and dimethyl thiosulfinate were optimally formed at pH 6.5-7.0 and pH
      5.5, respectively. Below pH 3.6 no thiosulfinates were formed. Neutralization of
      the pH failed to restore thiosulfinate generation from garlic previously
      incubated at pH 3 or below. Thus, alliinase is completely and irreversibly
      inhibited by the acidic conditions found in the stomach. The dipropenyl
      thiosulfinates were completely formed in 0.3 min at 37 degrees C, while the
      methyl thiosulfinates were not completely formed until 3.5 min. Allyl 1-propenyl
      thiosulfinate was the most rapidly formed, and the most unstable, thiosulfinate.
      The stability of the dipropenyl thiosulfinates was improved at pH 4.5 or lower.
      Drying garlic at 60 degrees C had no effect on alliin or the rate of formation of
      the dipropenyl thiosulfinates, but decreased trans-1-propenylcysteine sulfoxide
      (isoalliin) and the rate of formation of the methyl thiosulfinates. The results
      demonstrate that there are two alliinase activities in garlic, that a stomach
      acid-resistant coating on garlic powder tablets is necessary for thiosulfinate
      release, and that carefully prepared garlic powder can release similar amounts of
      total thiosulfinates to whole garlic cloves.

PMID- 17226484
TI  - New Flavonoid Glycosides from Arnicae Flos DAB 91.
AB  - Five flavonoid glycosides were identified from flowers of Arnica montana, ten
      from A. CHAMISSONIS subsp. FOLIOSA var. INCANA. The structures were established
      on the basis of acid hydrolysis and spectral data (UV, NMR, MS) as the 7-beta
      glucosides of pectolinarigenin, apigenin, and chrysoeriol; luteolin 3'- O-beta
      glucoside; the 3-beta-glucuronides of kaempferol, isorhamnetin, and 6
      methoxykaempferol; the 3,7-di-beta-glucosides of quercetin and patuletin; the 3
      beta-glucosides of betuletol and quercetagetin 6,3',4'-trimethyl ether; and the 7
      [6''- O-(2-methylbutyryl)]=glucosides of luteolin and eupafolin. The latter four
      are new natural compounds. Differences between these two ARNICA species are
      discussed.

PMID- 17226485
TI  - New Ecdysteroids from Serratula tinctoria.
AB  - Six new ecdysteroids have been isolated from SERRATULA TINCTORIA; these are: the
      2,22- and 3,22-diacetates of 20-hydroxyecdysone, 5beta-hydroxyrubrosterone, 3-epi
      poststerone, 3-epi-rubrosterone, and 22-oxo-20-hydroxyecdysone. These minor
      compounds were found together with the known ecdysteroids, 20-hydroxyecdysone,
      its 2-, 3-, and 22-monoacetates, rubrosterone, poststerone, polypodine B
      (5beta,20-dihydroxyecdysone), pterosterone (25-deoxy-20,24-dihydroxyecdysone),
      and makisterone C (24-ethyl-20-hydroxyecdysone). All these ecdysteroids were
      isolated by a combination of several chromatographic techniques (liquid
      chromatography on alumina, DCCC, and HPLC), then identified using standard mass
      spectrometric and 2D (1)H-NMR techniques.

PMID- 17226486
TI  - New Eremophilane Type Lactones from the Roots of Ligularia veitchiana.
AB  - Phytochemical investigation of the roots of LIGULARIA VEITCHIANA has resulted in
      the characterization of two new eremophilanolides together with beta-sitosterol,
      stigmasterol, taraxol, and liguhodgsonal whose structure was further confirmed by
      the (13)C-NMR techniques. The structures of the new constituents were elucidated
      by spectroscopic methods and shown to be 1beta, 10beta-epoxy-6beta(2'
      hydroxymethylacryloyloxy)-8beta-hydroxy-eremophila-7(11)-en-12,8alpha-olide ( 1)
      and 1beta, 10beta-epoxy-6beta-(2'-hydroxymethylacryloyloxy)-8beta-ethoxy
      eremophila-7(11)-en-12,8alpha-olide ( 2).

PMID- 17226487
TI  - Salutaridine N-Oxide from the Capsules of Papaver bracteatum.
AB  - A novel compound, salutaridine N-oxide ( 1) has been isolated from PAPAVER
      BRACTEATUM Lindl (Papaveraceae) in which the major alkaloids were salutaridine
      and thebaine. Semisynthetic 1 was prepared for structure confirmation. Other
      components of the alkaloidal fraction were isothebaine, oripavine, neopine, and
      thebaine N-oxide.

PMID- 17226488
TI  - Eudesmanolides and Other Constituents from Artemisia argyi.
AB  - The phytochemical investigation of the aerial parts of ARTEMISIA ARGYI afforded
      beta-sitosterol, stigmasterol, alpha-amyrin, beta-amyrin, friedelin, naringenin,
      quercetin, and four eudesmane derivatives, two of which were new eudesmanolides.
      The structures of the novel compounds were elucidated by high field NMR
      techniques.

PMID- 17226489
TI  - Structural Elucidation of Dendranthemosides A and B: Two New beta-Ionone
      Glucosides from Dendranthema shiwogiku.
AB  - From the N-BuOH soluble fraction of an MeOH extract of DENDRANTHEMA SHIWOGIKU,
      two new beta-ionone glucosides and roseoside were isolated, the structures of the
      new compounds elucidated were 2 and 3, respectively, on the basis of
      spectroscopic data and the results of an enzymic hydrolysis of 2.

PMID- 17226490
TI  - Chemical Varieties of Essential Oils from Elsholtzia polystachya from Two
      Different Locations in India1.
AB  - Capillary GC, GC-MS, IR, GC-IR, (1)H- and (13)C-NMR studies of the essential oil
      from the leaves and cones of ELSHOLTZIA POLYSTACHYA collected from two different
      locations in India revealed that one oil contained 1,8-cineol (37.3%), the other
      one perillene (61.2%) as the main constituent.

PMID- 17226491
TI  - Neolignans, Norneolignans, and Other Components from Krameria sonorae1.

PMID- 17226492
TI  - Polyprenyl Hydroquinones from Croogomphus rutilus.

PMID- 17226493
TI  - Further studies on drying willow (salix) twigs: the effect of low drying
      temperature on labile phenolics.

PMID- 17226494
TI  - Volatile Oil Constituents of Dennettia tripetala.

PMID- 17226495
TI  - Triterpenoids and Steroids from Aster poliothamnus.

PMID- 17226496
TI  - Isolation of 1,2-Epoxypulegone from Acrocephalus indicus.

PMID- 17226497
TI  - Isolation, Identification, and Chemical Synthesis of 6alpha-Hydroxyraumacline: A
      Novel Alkaloid from Cultivated Rauwolfia serpentina Cells.
AB  - From RAUWOLFIA SERPENTINA cells cultivated in the presence of ajmaline ( 2) the
      new indole alkaloid, 6alpha-hydroxyraumacline ( 1), was isolated. This alkaloid
      also occurs in significant amounts in the nutrition medium. A simple chemical
      synthesis of 1 was developed starting from ajmaline ( 2).

PMID- 17226498
TI  - Concentration of Ginkgolides and Bilobalide in Ginkgo biloba Leaves in Relation
      to the Time of Year.
AB  - The concentrations of ginkgolides A, B, and C, and bilobalide were determined in
      the leaves of 3 different Dutch GINKGO BILOBA trees from late spring until late
      autumn 1990. The concentration versus harvest time plots were roughly the same
      for all the compounds in each of the 3 trees. Concentration was lowest in spring
      and then gradually increased until a maximum in late summer or early autumn was
      reached. Thereafter the concentration declined until leaf fall. The difference in
      ginkgolide and bilobalide content between the 3 trees was very high. For
      ginkgolide B, the pharmacologically most potent compound, the maximum
      concentration was less than 3, 68 and 204 ppm respectively. Possible reasons for
      these differences and consequences for phytotherapy are discussed briefly.

PMID- 17226499
TI  - Influence of the 70% methanolic extract from red ginseng on the lysosome of tumor
      cells and on the cytocidal effect of mitomycin c1.
AB  - The influence of the 70% methanolic extract (RMe) from Red Ginseng on the
      lysosome of tumor cells and on the cytocidal effect of mitomycin C (MMC) was
      investigated. RMe treatment showed an inhibitory effect on the solid form of
      Ehrlich ascites carcinoma but had no effect on the ascites form. MMC combined
      with RMe showed stronger antitumor effects, at the same time, the activity of
      lysosomal enzymes in tumor cells was also increased in comparison with that
      treated with MMC alone. Furthermore, RMe promoted the uptake of MMC into the
      tumor cells and enhanced IN VITRO the cytotoxicity of MMC against the cultured
      tumor cells. From these results it was concluded that RMe labilized the lysosomes
      of tumor cells IN VIVO, and increased the uptake of MMC into the tumor cells, and
      that the cytocidal effect of MMC was enhanced by concomitant treatment with RMe.

PMID- 17226500
TI  - The Constitution and Configuration of Isocaryophyllen-13-al.
AB  - The aerial parts of CUNILA SPICATA Benth., a Brasilian Lamiaceae, afforded a
      sesquiterpene-aldehyde named isocaryophyllen-13-al (beta-betulenal) ( 1). The
      constitution and configuration of this compound were established by high field
      NMR-techniques for the first time.

PMID- 17226501
TI  - Epimeric (20R,20S)-Verazine Isolated from Veratrum maackii: Two-Dimensional NMR
      Studies and Total Assignment of 1H- and 13C-Resonances.
AB  - (13)C-NMR evidence shows that verazine [(25 S)-iminocholesta-5,22( N)-diene-3beta
      ol] isolated from the Chinese plant VERATRUM MAACKII (Melanthiaceae) consists of
      a 20 R/20 S mixture of epimers. The determination of the configurations at the
      chiral epimeric center and of the conformation of the 17beta-side chain is based
      on the total assignment of the (13)C- and (1)H-NMR resonances. This goal was
      achieved by the extensive use of homo- and heteronuclear shift correlation and
      two-dimensional NOE spectroscopy methods at high magnetic field.

PMID- 17226502
TI  - On the botanical distribution of chiral forms of gossypol.
AB  - Plants belonging to Malvaceae (about 90 species belonging to 33 genera) were
      analysed for the presence of gossypol by reversed-phase HPLC using absorbance
      detection at 365 nm, and the chirality and optical purity of gossypol were
      determined whenever the analysis was positive. Only plants belonging to the
      cotton tribe (Gossypieae) contained gossypol (detection limit better than
      0.001%). In particular, no gossypol could be detected in ABELMOSCHUS ESCULENTUS
      (ocra), HIBISCUS TILIACEUS, H. SABDARIFFA, and HEREA BRASI-LIENSIS, earlier
      claimed to contain this compound. Gossypol-containing plants usually produced
      dextrorotatory gossypol of varying optical purity; an enantiomeric excess of (-)
      gossypol was detected in only one plant, GOSSYPIUTN BARBADENSE.

PMID- 17226503
TI  - Sesquiterpene Lactones and Other Constituents from Artemisia feddei.
AB  - The aerial parts of ARTEMISIA FEDDEI Levl. et Vant., common in the NW of China,
      contain several widespread plant constituents and five sesquiterpene lactones two
      of which are new guaianolides. The structures were elucidated by spectroscopic
      methods.

PMID- 17226504
TI  - The volatiles of two bystropogon species from the canary islands (Spain).
AB  - The essential oils of two BYSTROPOGON species of the mint family endemic to the
      Canary Islands (Spain) have been analyzed by a combination of GLC/MS, retention
      indices, 1R, (13)C-NMR and (1)H-NMR spectra. The major components of the volatile
      oils were found to be pulegone, isomenthone, and methone in B. ORIGANIFOLIUS and
      3-octyl acetate, limonene, and TRANS-beta-caryophyllene in B. CANARIENSIS.

PMID- 17226505
TI  - Diterpenoid Constituents of Rabdosia longituba.

PMID- 17226506
TI  - A New Hemiterpene Glucoside from Ornithogalum montanum.

PMID- 17226507
TI  - Isolintetralin: A New Lignan from Phyllanthus niruri.

PMID- 17226508
TI  - Guaianolide Glucosides from Elephantopus scaber.

PMID- 17226509
TI  - Protoalkaloids from Boscia angustifolia.

PMID- 17226510
TI  - (+)-Norchelidonine from Chelidonium majus.

PMID- 17226511
TI  - An Oxygenated Tetrahydrobergamotene from the Essential Oil of Dracocephalum
      nutans*.

PMID- 17226512
TI  - Composition of the Essential Oil of Cymbopogon coloratus*.

PMID- 17226514
TI  - Hydroxycoumarins from Fraxinus ornus Bark.

PMID- 17226513
TI  - Studies on the Chemical Constituents of Kalopanax septemlobus.

PMID- 17226516
TI  - Baton exchange.

PMID- 17226515
TI  - Penicillium camemberti A New Source of Brefeldin A.

PMID- 17226517
TI  - Procyanidin Production by Fagopyrum esculentum Callus Culture.
AB  - FAGOPYRUM ESCULENTUM CALLUS cultures grown on B5 medium synthesize procyanidins
      B2 (0.6-1.8 mg/g dry wt) and B2-3'- O-gallate (3.5-6.0 mg/g dry wt). Sucrose is a
      better source than other carbohydrates and moderate concentrations (3-4%)
      stimulate both growth and procyanidin synthesis. While darkness was not a
      limiting factor, light induced faster growth and increased procyanidin contents.
      Treatment with gallic acid strongly stimulated the procyanidin B2-3'- O-gallate
      production, but drastically inhibited growth, leading to a two-step-culture
      experiment combining convenient growth and increased galloylated dimer synthesis
      (up to 45 mg/g dry wt).

PMID- 17226518
TI  - The Norcoclaurine Pathway is Operative in Berberine Biosynthesis in Coptis
      japonica.
AB  - The commercially used cell suspension culture of COPTIS JAPONICA Makino
      (Ranunculaceae) incorporates [beta- (13)C]tyrosine into both halves of the
      berberine molecule (isoquinoline and benzyl portion) while L-[3'- (18)O]DOPA only
      labels the isoquinoline portion of this molecule. This labelling pattern
      indicates that different C (6)-C (2) units derived from tyrosine form this
      molecule. This result and the incorporation of ( S)-[1- (13)C] norcoclaurine into
      berberine demonstrates that the biosynthesis of protoberberine alkaloids in
      COPTIS involves the norcoclaurine but not the norlaudanosoline pathway.

PMID- 17226519
TI  - Immunostimulant Activity of Picroliv, the Iridoid Glycoside Fraction of
      Picrorhiza kurroa, and its Protective Action against Leishmania donovani
      Infection in Hamsters1.
AB  - Picroliv, a standardised fraction from root and rhizome of PICRORHIZA KURROA,
      consisting of iridoid glycosides and shown to be responsible for its
      hepatoprotective activity, was studied for immunostimulant activity. Oral
      administration of Picroliv (10 mg/kg x 7 days) in mice prior to immunization with
      sheep red blood cells (SRBC) resulted in a significant increase in
      haemagglutinating antibody (HA) titre, plaque forming cells (PFC), and delayed
      hypersensitivity (DTH) response to SRBC. Picroliv enhanced the non-specific
      immune response characterized by an increase in macrophage migration index (MMI),
      [ (14)C]-glucosamine uptake, phagocytosis of [ (14)C]-leucine labelled
      ESCHERICHIA COLI, chemiluminescence of peritoneal macrophages, and higher uptake
      of [ (3)H]-thymidine in the lymphocytes of treated mice. It also induced a high
      degree of protection in golden hamsters against challenge infection with
      LEISHMANIA DONOVANI promastigotes.

PMID- 17226520
TI  - Jasamplexosides A, B and C: Novel Dimeric and Trimeric Secoiridoid Glucosides
      from Jasminum amplexicaule.
AB  - Three new secoiridoid glucosides, jasamplexosides A, B and C, were isolated from
      the crude drug "Niu du teng", the leaves and stems of JASMINUM AMPLEXICAULE,
      together with the known secoiridoid glucosides, 10-hydroxyligstroside and
      jasminoside. Their structural elucidation by spectroscopic studies is described.

PMID- 17226521
TI  - Tussilagine and isotussilagine: two pyrrolizidine alkaloids in the genus arnica1.
AB  - In flowerheads of ARNICA MONTANA, A. CHAMISSONIS ssp. FOLIOSA, A. AMPLEXICAULIS,
      and A. SACHALINENSIS, traces of the non-toxic pyrrolizidine alkaloids tussilagine
      and isotussilagine were detected. Their identity was unambiguously confirmed by
      direct comparison (TLC, GC, GC/MS) with the authentic samples.

PMID- 17226522
TI  - Genetic Variability of the Essential Oil Content of Melissa officinalis1.
AB  - The essential oil content of various populations of MELISSA OFFICINALIS L.
      (Lamiaceae), cultivated under Mediterranean climatic conditions (Ebro-Delta,
      Spain) has been investigated during five years of selection and improvement of
      the genetic plant material. Starting with an essential oil content of 0.2-0.3%, a
      content of more than 0.5% was obtained as a result of genetic improvement. A weak
      negative correlation between the content of essential oil and phenotypical growth
      parameters such as the number of branches per plant and height was observed. No
      correlation between biomass production per plant and essential oil content could
      be found. By the method of hybridization, M. OFFICINALIS synthetics with a high
      yield of biomass and essential oil content were selected.

PMID- 17226523
TI  - Content and Composition of M. officinalis Oil in Relation to Leaf Position and
      Harvest Time1.
AB  - The content and composition of the essential oil in the leaves of M. OFFICINALIS
      L. (Lamiaceae) cultivated under Mediterranean climatic conditions were
      investigated. Different leaf positions and different times of harvest during the
      year and during the day were considered. It was shown that in the terminal
      leaves, the content of essential oil was more than 0.1% higher than in the
      others. The results obtained also indicated a variation of the oil composition.
      The favourable climatic and environmental conditions of the Ebro-Delta in Spain
      permitted four harvests per year with a maximum of 0.4% essential oil in
      September. To reduce losses of volatile terpenoids, a harvest in the morning
      during summertime is recommended.

PMID- 17226524
TI  - Phthalides and Monoterpenes of the Hexane Extract of the Roots of Ligusticum
      porteri1.

PMID- 17226525
TI  - Phenolic Constituents of Wikstroemia retusa.

PMID- 17226526
TI  - New Constituents from Ocimum sanctum.

PMID- 17226727
TI  - [Test of mask acceptance (MAT) in elderly patients with obstructive sleep apnea].

PMID- 17226729
TI  - [Role of epigenetics in the carcinogenesis of head and neck carcinomas - possible
      new targeted therapy?].
AB  - In search of new targeted therapies for squamous cell carcinoma of the head neck
      (HNSCC), a better understanding of the carcinogenesis is of outmost importance.
      Recent studies show that not only genetic but also epigenetic alterations
      initiate the multistep process of tumordevelopment. Epigenetic changes lead to
      altered gene expression without alterations of the DNA sequence. The best
      characterized epigenetic change is the methylation of the promoter region of
      genes, especially of tumorsuppressor genes. The methylation of the promoter
      region blocks the promoter and therefore represses transcription. The loss of the
      gene products of tumorsuppressor genes leads to increased proliferation and
      decreased apoptosis. Methylation of tumorsuppressor genes was shown in
      precancerous lesions of HNSCC, which emphasizes the importance of methylation as
      an early biomarker. Several studies of tumor cell cultures show reactivated
      expression of proteins and as a result reduction of proliferation and induction
      of apoptosis after treatment with demethylating agentens. This presents a very
      promising new option for a targeted therapy.

PMID- 17226731
TI  - [Screening of modified polyethylene surfaces for tissue engineering of
      chondrocytes].
AB  - BACKGROUND: Reconstructive surgery needs high requirements of substitutes for
      cartilages. The availability of autologous material is limited. The use of
      implants can cause inflammatory reactions. Therefore the biocompatibility of
      porous polyethylene should be improved by masking the synthetic surface with
      autologous cells. The polyethylene surface was functionalized by collagen, in
      order to enhance the contact between polyethylene and the surrounding cells.
      METHODS: The modified surfaces were characterized and tested by an in vitro
      screening with primary human chondrocytes. RESULTS: The modification of
      polyethylene surfaces by collagen coating increased the life time of chondrocytes
      growing at this surface. The effect was independent of the former
      functionalization. CONCLUSIONS: It is possible to cultivate chondrocytes on
      polyethylene surfaces. The results have to be proven in a long-term animal
      experimental study.

PMID- 17226732
TI  - [Medical informations about risks of removing the cerumen].

PMID- 17226733
TI  - [Tumors of the eyelids].

PMID- 17226737
TI  - Neuropsychology of cortical versus subcortical dementia syndromes.
AB  - Neuropsychological studies have shown that there are several prominent
      differences in the patterns of cognitive deficits that occur in neurodegenerative
      disorders that have their primary etiology in either cortical or subcortical
      brain dysfunction. Quantitative and qualitative differences are apparent across
      many cognitive domains, including memory (in all its aspects), attention,
      executive functions, language and semantic knowledge, and visuospatial abilities.
      These distinct patterns of deficits have been broadly characterized as forming
      cortical and subcortical dementia syndromes. Differentiating between cortical and
      subcortical dementia provides a heuristically useful model for understanding
      brain-behavior relationships in neurodegenerative diseases and may improve the
      ability to clinically distinguish among various dementing disorders.

PMID- 17226738
TI  - Mild cognitive impairment: current research and clinical implications.
AB  - Mild cognitive impairment refers to the transitional state between the cognitive
      changes of normal aging and the fully developed clinical features of dementia.
      This topic has received a great deal of attention in the literature in recent
      years and is being proposed for clinical applications as well. Clinical
      guidelines, including the original memory-focused criteria and the more recent
      broadly defined set of criteria, will be presented. The clinical outcome of
      individuals with mild cognitive impairment will be discussed and several
      explanations for variability in the literature will be considered. Predictors of
      progression, including genetic, neuroimaging, biomarker, and clinical
      characteristics, will be presented, as will the controversies regarding the
      underlying neuropathology of mild cognitive impairment. The recently completed
      mild cognitive impairment clinical trials will be discussed and the lessons
      learned from them translated into recommendations for future investigations.
      Finally, the clinical utility of mild cognitive impairment, its incorporation
      into clinical practice, and directions for future research will be proposed.

PMID- 17226739
TI  - Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in the elderly.
      Currently, 4.5 million individuals in the United States are estimated to have AD,
      and that number is projected to increase to at least 14 million by the year 2050.
      AD is a major cause of disability and mortality, and its impact on health care
      costs, including direct and indirect medical and social service costs, is
      estimated to be greater than $100 billion per year. AD typically presents with an
      insidious decline in memory that progresses to affect language, visuospatial
      perception, calculations, and executive functioning. Behavioral and psychiatric
      symptoms are also frequent in AD. Diagnosis is determined clinically, as there is
      currently no laboratory test to confirm AD in life. The neuropathologic hallmarks
      of AD are neuritic plaques and neurofibrillary tangles. Currently available
      medical therapies have demonstrated modest benefits but likely do not alter
      disease progression. Caregivers play a large role in managing the patient and
      should be encouraged to seek out adult day care centers, home health services,
      respite care, and additional social support.

PMID- 17226740
TI  - Dementia with Lewy bodies.
AB  - Synucleinopathies, with and without dementia, encompass a wide range of diseases
      including Parkinson's disease, multiple system atrophy, rapid eye movement (REM)
      sleep behavior disorder, and dementia with Lewy bodies (DLB). DLB is a
      neurodegenerative disorder resulting in slowly progressive and unrelenting
      dementia until death. Prevalence studies suggest that it is the second most
      common dementing illness in the elderly. The neuropathologic findings of DLB show
      a wide anatomic range. Lewy bodies and Lewy-related pathology are found from the
      brain stem to the cortex and, in many cases, associated with concurrent
      Alzheimer's disease pathology. A recent international consortium on DLB has
      resulted in revised criteria for the clinical and pathological diagnosis of DLB
      incorporating new information about the core clinical features and improved
      methods for their assessment. The presentation of DLB is typically one of
      cortical and subcortical cognitive impairments, with worse visuospatial and
      executive dysfunction than Alzheimer's disease. There may be relative sparing of
      memory especially in the early stages. Core clinical features of DLB include
      fluctuating attention, recurrent visual hallucinations, and parkinsonism.
      Suggestive features include REM sleep behavior disorder, severe neuroleptic
      sensitivity, and low dopamine transporter uptake in the basal ganglia on
      functional neuroimaging. Additional supportive features that commonly occur in
      DLB, but with lower specificity, include repeated falls and syncope, transient,
      unexplained loss of consciousness, severe autonomic dysfunction, hallucinations
      in other modalities, systematized delusions, depression, relative preservation of
      medial temporal lobe structures on structural neuroimaging, reduced occipital
      activity on functional neuroimaging, prominent slow wave activity on
      electroencephalogram, and low uptake myocardial scintigraphy. Management of DLB
      includes pharmacological and nonpharmacological interventions for its cognitive,
      neuropsychiatric, motor, and sleep disturbances.

PMID- 17226741
TI  - Frontotemporal dementia.
AB  - Frontotemporal dementia (FTD) is an uncommon but important form of degenerative
      disease. It may make up 50% of dementia cases presenting before age 60. The
      symptoms are related to the anatomic areas affected. Neary divided the clinical
      syndromes into "frontotemporal dementia," "progressive nonfluent aphasia," and
      "semantic dementia." However, the pathology may extend beyond the frontal and
      temporal lobes and additional symptoms may be found. Although most cases are
      sporadic, some cases are genetic. The best-known genetic mutation causing FTD is
      frontotemporal dementia with parkinsonism, linked to the microtubule-associated
      protein tau on chromosome 17. There are other known genes and chromosome loci
      related to FTD. The most common pathology found is frontotemporal degeneration
      with ubiquitin inclusions. In contrast, FTD with Pick bodies is rare. Although
      there are strategies to help patients and their families, there is no known
      treatment for the disease.

PMID- 17226742
TI  - Normal pressure hydrocephalus.
AB  - Idiopathic normal pressure hydrocephalus (INPH) is a treatable neurological
      disorder in older adults involving disturbances of gait/balance, control of
      micturition, and/or cognition in combination with enlargement of the cerebral
      ventricles. Diagnosis can be challenging due to its varied presentation and
      overlap with other disorders common in the elderly. Evidence-based consensus
      guidelines for diagnosis and treatment of INPH have been created that can assist
      in clinical management. Diagnosis requires clinical documentation of one or more
      of the characteristic symptoms of INPH in combination with a brain imaging study
      demonstrating nonobstructive ventricular enlargement disproportionate to cerebral
      atrophy. Gait and balance disturbances are the most common presenting findings in
      INPH and may occur alone or together with cognitive and urinary symptoms. Adjunct
      tests, particularly those involving transient removal of cerebrospinal fluid via
      lumbar puncture or lumbar drain, can serve the dual purpose of adding to
      diagnostic certainty and assisting in prognostication about response to
      treatment. Prognostication is important because neurosurgical treatment by
      placement of a ventricular shunt, while effective, carries the risk of
      potentially significant morbidity. Outcome of shunting in INPH is most often
      successful when patients are accurately diagnosed, suitably evaluated for
      surgical candidacy, and managed carefully throughout the preoperative, surgical,
      and postoperative periods.

PMID- 17226743
TI  - Vascular dementia: emerging trends.
AB  - Vascular dementia is a term used to describe a constellation of cognitive and
      functional impairment that can be viewed as a subset of the larger syndrome of
      vascular cognitive impairment associated with cerebrovascular brain injury.
      Vascular dementia is a common disorder among the elderly, although it can also
      occur in younger persons. Comprising 20% of all cases of dementia in the United
      States, vascular dementia is the second most common form of dementia after
      Alzheimer's disease. Patients with vascular dementia often exhibit mood and
      behavioral changes and may have focal neurological signs on neurological
      examination. Primary treatment is through primary or secondary modification of
      cerebrovascular risk factors such as hypertension, although symptomatic
      treatments with cholinesterase inhibitors have shown modest symptomatic benefit.

PMID- 17226744
TI  - Multiple sclerosis.
AB  - Multiple sclerosis (MS) is a demyelinating disease of the central nervous system
      that commonly leads to inflammatory and atrophic brain pathology, often causing
      cognitive impairment. MS-associated cognitive impairment was first described over
      a century ago. However, with the advent of standardized neuropsychological
      testing and quantitative brain imaging, the frequency, quality, and correlates of
      cognitive impairment are better understood. Dementia is rare in MS, although it
      is known to occur in 10 to 25% of patients. Our data suggest a frequency of 22%
      among clinic attendees. In addition to the cognitive impairments evident in MS
      dementia, changes in personality and social behavior also occur. For example,
      some patients develop euphoria sclerotica and marked deficiency in social
      empathy, conditions that in combination with executive dysfunction cause
      considerable hardship for patients and caregivers. These neuropsychiatric
      manifestations of MS dementia are correlated with magnetic resonance imaging
      indicators of brain atrophy, including ventricle enlargement, neocortical volume,
      and normalized whole brain volume. Recent developments in pharmacological
      treatment for disease progression and management of cognitive symptoms hold
      promise for patients suffering from the degenerative aspects of MS.

PMID- 17226745
TI  - Dementia and neurocognitive disorders due to HIV-1 infection.
AB  - Human immunodeficiency virus-type 1 (HIV-l) infection is the most common
      preventable and treatable cause of neurocognitive impairment in individuals under
      age 50 years. Although the incidence of HIV-associated dementia has decreased
      over the past few years due to combination antiretroviral therapy (cART), the
      prevalence of less severe HIV-associated neurocognitive impairment continues to
      increase. HIV-associated neurocognitive impairment is a significant burden to
      persons living with HIV infection, caregivers, and the health care system.
      Neurocognitive changes associated with HIV are typically subcortical, consisting
      of the triad of cognitive, behavior, and motor dysfunction. HIV-associated
      dementia and HIV-associated neurocognitive impairment are clinical diagnostic
      syndromes with neuropsychological performance testing, neuroimaging, and cerebral
      spinal fluid studies providing additional information. With the advent of more
      effective cART, the incidence of fatal opportunistic complications has
      dramatically diminished. Accordingly, the present review focuses on primary HIV
      induced disease of the central nervous system, rather than its opportunistic
      complications.

PMID- 17226747
TI  - Molecular dynamics study of the conformational dynamics and energetics of some
      large-ring cyclodextrins (CDn, n = 24, 25, 26, 27, 28, 29).
AB  - Molecular dynamics simulations in water solution were performed on six large-ring
      cyclodextrins (LR-CDs) with a degree of polymerization 24, 25, 26, 27, 28, and
      29. The AMBER parm99 force field and explicit water molecules (TIP3P) were used
      in the simulations. The present research was aimed at further extending our
      knowledge on the structural dynamics and the energetics of this new class of
      compounds that may eventually provide chiral cavities suitable for formation of
      inclusion complexes with small molecules, and, accordingly, to serve as host
      structures for chiral recognition. The study focused on several representatives
      flanking CD26-the largest LR-CD for which X-ray data is available. Both the
      monitoring of the structural variations during the simulations as well as the
      analyses of energy balances are indicative for high flexibility of the
      macrorings. Slight differences of the overall preferred shapes were detected with
      diminishing the size of the macromolecules from CD29 to CD24. An elongated cavity
      (CD28) or a double parallel strand in different specific representations are the
      dominating motifs in the LR-CDs studied: with loops at the two ends (CD25, CD28,
      CD29), with a loop at one end (CD25), twisted (CD26, CD27) or twisted with an
      open portion in the middle (CD24), helical (CD24, CD25), or linking two loops
      from one of their sides (CD27). Two loops connected by an arc (CD28, CD29) and a
      cavity with the shape of an extended rectangular (CD24, CD28) appear
      preferentially during the conformational interconversions of the two larger CDs,
      whereas helical motifs are present in the smaller macrorings: an extended helix
      with ends linked by an arc (CD24), helical turn and helical portion (CD26, CD27).
      A triple propeller conformation or three symmetrical loops of almost equal size
      were also detected for CD26 and CD29, respectively. The present results further
      support the hypothesis for the existence of more than one cavity in large-ring
      cyclodextrins and suggest preferred conformations in water solution for the LR
      CDs with degree of polymerization from 24 to 29.

PMID- 17226746
TI  - A battery of DNA effect biomarkers to evaluate environmental exposure of Flemish
      adolescents.
AB  - The present paper deals with the evaluation of a battery of genotoxicity
      biomarkers in healthy Flemish adolescents and their relation with common
      pollutants occurring in their life environment. DNA damage as reflected by the
      comet assay appeared to be most sensitive to ozone (partial r(2) = 0.102, p <
      0.00001), and to a lesser extent to ortho-cresol (partial r(2) = 0.055; p =
      0.001) and 1-hydroxy-pyrene (1-OH-pyrene, partial r(2) = 0.031; p = 0.013). 8
      hydroxy-deoxyguanosine (8-OHdG) was only related to ortho-cresol (r(2) = 0.069; p
      < 0.007). Interestingly, the comet assay results and urinary 8-OHdG
      concentrations were positively correlated with a Pearson r = 0.21 (p = 0.003, N =
      200). Logistic regression models revealed significant relations between chromatid
      breaks and 1-OH-pyrene (relative risk (RR): 1.58; p = 0.008), and t,t-muconic
      acid (RR: 1.71; p = 0.014). There was no correlation between micronucleus
      formation or occurrence of chromosomal or chromatid breaks on the one hand and
      comet or 8-OHdG results on the other hand. Thus, in this study the comet assay on
      whole blood samples and urine 8-OHdG measurements especially appeared sensitive
      biomarkers for assessing the genetic effects of environmental pollutants to which
      adolescents may be exposed.

PMID- 17226748
TI  - Enantioselective preparative HPLC separation of the HBCD-Stereoisomers from the
      technical product and their absolute structure elucidation using X-ray
      crystallography.
AB  - 1,2,5,6,9,10-Hexabromocyclododecane (HBCD) is a widely used flame retardant,
      which tends to persist in the environment and accumulates in biota. The six
      stereoisomers (three racemates named alpha-, beta-, and gamma-HBCD) of the
      technical mixture were isolated with high-performance liquid chromatography
      (HPLC). Direct separations were performed on a chiral stationary phase containing
      permethylated beta-cyclodextrin (NUCLEODEX beta-PM column) and the pure
      enantiomers of alpha-, beta-, and gamma-HBCD were physically characterized for
      the first time. The absolute configurations of all six isomers were determined by
      anomalous dispersion using single crystal X-ray crystallography. Optical
      rotations alphaD in tetrahydrofuran were +4.2/-4.0 (alpha-HBCD), +26.1/-27.5
      (beta-HBCD), and +68.0/-66.3 (gamma-HBCD). The sense of rotation could be
      correlated with the absolute configurations of alpha-, beta-, and gamma-HBCD
      enantiomers and their order of elution on a chiral permethylated beta
      cyclodextrin-bonded stationary phase. The diastereomersalpha-, beta-, and gamma
      HBCD displayed distinctly different melting points as well as (1)H-, (13)C NMR,
      and IR spectra.

PMID- 17226749
TI  - Evidence for multiple signaling pathways in single squid olfactory receptor
      neurons.
AB  - At least two different G-protein-mediated transduction cascades, the adenylate
      cyclase and phospholipase C (PLC) pathway, process chemosensory stimuli for
      various species. In squid olfactory receptor neurons (ORNs), physiological
      studies indicate that both pathways may be present; however, confirmation of the
      transduction molecules at the protein level is absent. Here we provide evidence
      that the G-proteins involved in both adenylate cyclase and PLC pathways are
      present in squid ORNs (Lolliguncula brevis). We used immunoblotting to show that
      Galpha(olf), Galpha(q), and a downstream effector, enzyme PLC140, are present in
      the squid olfactory epithelium (OE). To localize these proteins to one or more of
      the five morphological cell types described for squid OE, paraformaldehyde-fixed
      olfactory organs were cryosectioned (10 microm), double-labeled for Galpha(olf),
      Galpha(q), or PLC140, and imaged. Analysis of serial sections from entire
      olfactory organs for epithelial area and patterns of immunofluorescence revealed
      a region of highest immunoreactivity at the anterior half of the organ. At the
      cellular level, type 1 cells could not be distinguished morphologically and were
      not included in the analysis. The three labeling patterns observed in type 2
      cells were Galpha(q) alone, PLC140 alone, and colocalization of Galpha(q) and
      PLC140. Subsets of cell types 3, 4, and 5 showed colocalization of Galpha(olf)
      with Galpha(q) but not with PLC140. These data suggest that the PLC pathway
      predominates in type 2 cells; however, coexpression of Galpha(olf) with Galpha(q)
      in cell types 3, 4, and 5 suggests that both pathways may participate in
      olfactory transduction in non-type 2 squid ORNs.

PMID- 17226750
TI  - Primary visual cortex volume and total neuron number are reduced in
      schizophrenia.
AB  - A number of studies that assessed the visual system in subjects with
      schizophrenia found impairments in early visual processing. Furthermore,
      functional imaging studies suggested changes in primary visual cortex activity in
      subjects with schizophrenia. Interestingly, postmortem studies of subjects with
      schizophrenia reported an increased density of neurons in the primary visual
      cortex (Brodmann's area 17, BA17). The observed changes in visual processing may
      thus be reflected in structural changes in the circuitry of BA17. To characterize
      the structural changes further we used stereological methods based on unbiased
      principles of sampling (Cavalieri's principle and the optical fractionator) to
      estimate the total volume and neuron number of BA17 in postmortem brains from 10
      subjects with schizophrenia and 10 matched normal comparison subjects. In
      addition, we assessed cortical thickness. We found a marked and significant
      reduction in total neuron number (25%) and volume (22%) of BA17 in the
      schizophrenia group relative to the normal comparison subjects. In contrast, we
      found no changes in neuronal density or cortical thickness between the two
      groups. Subjects with schizophrenia therefore have a smaller cortical area
      allocated to primary visual perception. This finding suggests the existence of a
      schizophrenia-related change in cortical parcellation.

PMID- 17226751
TI  - CCK1 and 2 receptors are expressed in immortalized rat brain neuroblasts:
      intracellular signals after cholecystokinin stimulation.
AB  - Cholecystokinin (CCK) is one of the most abundant neuropeptides in the central
      nervous system (CNS) where it promotes important functions by activation of
      receptors CCK1 and CCK2. Our aim was to investigate CCK receptors expression and
      their downstream intracellular signaling in immortalized rat brain neuroblasts.
      Results show that CCK1 and CCK2 receptor mRNAs and CCK2 receptor protein are
      expressed in neuroblasts. CCK incubation of neuroblasts leads to stimulation in a
      time-dependent manner of several signaling pathways, such as tyrosine
      phosphorylation of adaptor proteins paxillin and p130(Cas), phosphorylation of
      p44/p42 ERKs as well as PKB (Ser473). Moreover, CCK-8 stimulates the DNA-binding
      activity of the transcription factor AP-1. The CCK2 receptor agonist gastrin
      stimulates ERK1/2 phosphorylation in a comparable degree as CCK does. ERK1/2
      phosphorylation activated by CCK-8 was markedly inhibited by the CCK2 receptor
      antagonist CR2945. Incubation for 48 h with CCK-8 increases neuroblasts viability
      in a similar degree as EGF. In summary, our data clearly identify CCK1 and CCK2
      receptor mRNAs and CCK2 receptor protein in brain neuroblasts and show that
      incubation with CCK promotes cell proliferation and activates the phosphorylation
      of survival transduction pathways. Stimulation of ERK1/2 phosphorylation by CCK
      is mainly mediated by the CCK2 receptor. Moreover, this work might provide a
      novel model of proliferating neuronal cells to further study the biochemical
      mechanisms by which the neuropeptide CCK exerts its actions in the CNS.

PMID- 17226752
TI  - Chitosan prevents the development of AOM-induced aberrant crypt foci in mice and
      suppressed the proliferation of AGS cells by inhibiting DNA synthesis.
AB  - We study the effect of fungal-derived chitosan on the development of chemical
      induced colonic precancerous lesions in ICR mice and delineate its possible
      molecular mechanisms. In the 2 weeks preventive experiments, mice fed with a diet
      containing high molecular weight chitosan (HMWC) had significant fewer aberrant
      crypt foci formation than those fed with control diet. As the treatment extended
      to 6 weeks, both low molecular weight chitosan (LMWC)- and HMWC-fed mice
      contained less aberrant crypt foci when compared to control. However, such effect
      was not observed in mice in the 6 weeks therapeutic experiments. The anti
      tumorigenesis effect of water-soluble chitosan oligomer (WSCO) was tested on four
      cancer cell lines. WSCO significantly suppressed AGS and to a less extent, COLO
      205 cells proliferation. Flow cytometry analysis of cell cycle distribution
      indicated that the percentage of S phase reduced significantly in AGS cells
      treated with WSCO together with a decrease in DNA synthesis rate in BrdU
      incorporation assay. WSCO treatment also upregulated cell cycle-related genes
      p21/Cip and p27/Kip, whereas downregulated that of PCNA.

PMID- 17226753
TI  - BMP-2 promotes differentiation of osteoblasts and chondroblasts in Runx2
      deficient cell lines.
AB  - To investigate the molecular mechanism underlying the differentiation of
      osteoblasts and chondroblasts, we established a clonal cell lines, RD-C6, from
      Runx2-deficient mouse embryos. RD-C6 cells expressed almost undetectable levels
      of phenotypes related to osteoblast and chondroblast differentiation at basal
      culture condition, whereas treatment with recombinant human bone morphogenetic
      protein-2 (rhBMP-2) or transduction of BMP-2 by adenovirus effectively induced
      this cell line to express mRNA related to the differentiation of osteoblasts and
      chondroblasts including alkaline phosphatase, osteocalcin, and osterix.
      Transduction of Runx2 also induced the expression of these mRNA in RD-C6 cells.
      BMP-2 transduction increased expression levels of mRNA for Msx2 and Dlx5, but
      Runx2 transduction induced no significant increases in expression levels of these
      mRNA. Microarray analysis using RD-C6 cells with or without rhBMP-2 treatment
      demonstrated that BMP-2 upregulated 66 genes including 13 transcription-related
      molecules such as Id1, Id2, Id4, Hey1, Smad6, Smad7, and Msx2. To confirm bone
      and cartilage formation ability of RD-C6 cells, we transplanted RD-C6 cells into
      the peritoneal cavity of athymic mice using diffusion chambers with rhBMP-2. RD
      C6 cells generated unmineralized cartilage but not bone. These results indicate
      that BMP-2 induces Runx2-deficient cells to express markers related to osteoblast
      and chondroblast differentiation using a Runx2-independent pathway, but it failed
      to induce these cells to differentiate into bone-forming osteoblasts and mature
      chondrocytes.

PMID- 17226754
TI  - Uppsalator's acceleration.
AB  - Semiquantitative prediction of the Uppsalator (electroosmotical oscillator
      developed in Uppsala) under constant voltage is confirmed via numerical solution
      of exact nonlinear integro-differential equations in partial derivatives (PDE).
      Critical voltage and characteristic features of pressure and liquid flow velocity
      as functions of time are reproduced with high precision. In particular, the
      number of inflection points per period of oscillating velocity increases with
      growing voltage from two to six. A new feature is demonstrated. For sufficiently
      high voltages the Uppsalator shows normal deceleration, i.e., the oscillation
      period grows with voltage. However, in some supercritical range of voltages,
      acceleration is observed, as expressed by decrease of the oscillation period with
      growing voltage. Thus, the Uppsalator at constant voltage considered earlier as
      an impossible phenomenon represents a great challenge for experimental
      verification.

PMID- 17226755
TI  - Andreas Chrambach and Rene Descartes: Plutarch's parallel lives?

PMID- 17226756
TI  - Investigation of hormone activity in butterfly imaginal wing discs by protein
      expression pattern changes.
AB  - In a proteomic approach using 2-DE, the changes in protein expression patterns in
      wing imaginal discs induced by hormone treatment have been studied. Here we show
      the response of butterfly imaginal wing disc tissue taken from late fifth instar
      larvae of the African-Mocker swallowtail Papilio dardanus (Lepidoptera) to the
      insect hormones 20-hydroxyecdysone (20-HE) and juvenile hormone (JH). The tissues
      were cultured in the presence of one hormone or a combination of both and their
      protein expression was compared to the pattern obtained from untreated wing
      discs. All the treatments resulted in changes in the expression pattern distinct
      from the uninduced control, indicating a distinct protein regulation induced by
      the hormones. The treatment with both of the hormones, which are known to have
      antagonistic physiological effects, did show a unique pattern, presumably the
      result, in part, of synergistic effects on protein expression mediated by the
      combined effects of both the hormones. The extent of the interaction between JH
      and 20-HE indicates a complex molecular regulation, far beyond a simple
      antagonistic effect.

PMID- 17226757
TI  - Shotgun electroelution: a proteomic tool for simultaneous sample elution from
      whole SDS-polyacrylamide gel slabs.
AB  - A high-throughput device has been constructed which allows parallel
      electroelution of separated SDS-protein bands directly from intact unsectioned
      polyacrylamide gel slabs as well as single electroelution of certain protein
      spots into a 384-well standard flat-bottom multiwell plate. The prototype
      provides complete, quick elution for proteomics from 1-D or from 2-D gels without
      gel sectioning. Since the elution chamber matrix requires no assembly, sample
      handling can be easily carried out by existing robotic workstations. The current
      design is a good candidate for automation of spot elution since there are no
      moving liquid containing components in the apparatus. Eight SDS-proteins were
      eluted in test runs and an average 70% sample recovery was achieved by re
      electrophoresis of the electro-eluates.

PMID- 17226758
TI  - pH transients during salt removal in isoelectric trapping separations: a curse
      revisited.
AB  - The pH transients that occur during isoelectric trapping separations as a result
      of the removal of nonampholytic ionic components have been re-examined. Salts
      containing strong electrolyte anions and cations, both with equal and dissimilar
      mobilities, have been studied using anodic and cathodic buffering membranes whose
      pH values were both equidistant and nonequidistant from pH 7. The direction and
      magnitude of the pH transient (acidic or basic) was found to depend on both the
      mobilities of the anion and cation (mu(anion)/mu(cation)) and the pH difference
      between pH 7 and the pH of the buffering membranes (|pH(memb) (anodic) - 7|/|7 -
      pH(memb) (cathodic)|). When |pH(memb) (anodic) - 7|/|7 - pH(memb) (cathodic)| =
      1, mu(anion)/mu(cation)<1 leads to an acidic pH transient, mu(anion)/mu(cation) =
      1 eliminates the pH transient and mu(anion)/mu(cation)>1 leads to a basic pH
      transient. When mu(anion)/mu(cation) = 1, |pH(memb) (anodic) - 7|/|7 - pH(memb)
      (cathodic)|<1 leads to a basic pH transient, |pH(memb) (anodic) - 7|/|7 -
      pH(memb) (cathodic)| = 1 eliminates the pH transient and |pH(memb) (anodic) -
      7|/|7 - pH(memb) (cathodic)|>1 leads to an acidic pH transient. By selecting
      appropriate anodic and cathodic buffering membranes to adjust the |pH(memb)
      (anodic) - 7|/|7 - pH(memb) (cathodic)| value, pH transients caused by dissimilar
      anion and cation mobilities can be avoided.

PMID- 17226759
TI  - A dynamic molecular probe to investigate catalytic effects and Joule heating in
      enantioselective MEKC.
AB  - Enantiomerization of ferroin [tris(1,10-phenanthroline)-iron(II)-complex] was
      investigated by enantioselective dynamic micellar EKC. The enantiomer separation
      was performed in an aqueous 50 mM sodium borate/sodium dihydrogenphosphate buffer
      at pH 8.0 in the presence of the chiral surfactant sodium cholate. The unified
      equation of dynamic chromatography was employed to determine reaction rate
      constants from the electropherograms featured with distinct plateau formation.
      Activation parameters DeltaH( not equal) = 124.0 +/- 0.5 kJ/mol and DeltaS( not
      equal) = 121 +/- 1 J.K(-1)mol(-1) were calculated from temperature-dependent
      measurements between 10.0 and 27.5 degrees C in 2.5 K steps. Considering the data
      obtained by polarimetry of enantiomeric pure ferroin in water, it was found that
      enantiomerization rate in the micelle is accelerated by a factor of 12. Because
      of the highly positive activation entropy DeltaS( not equal), ferroin was used as
      a temperature-sensitive dynamic molecular probe to determine temperature
      deviations caused by Joule heating.

PMID- 17226760
TI  - Decreased EXT expression and intracellular accumulation of heparan sulphate
      proteoglycan in osteochondromas and peripheral chondrosarcomas.
AB  - Mutational inactivation of EXT1 or EXT2 is the cause of hereditary multiple
      osteochondromas. These genes function in heparan sulphate proteoglycan (HSPG)
      biosynthesis in the Golgi apparatus. Loss of heterozygosity of the EXT1 locus at
      8q24 is frequently found in solitary osteochondromas, whereas somatic mutations
      are rarely found. We investigated the expression of EXT1 and EXT2 (quantitative
      RT-PCR) and of different HSPGs (immunohistochemistry) in solitary and hereditary
      osteochondromas and in cases with malignant progression to secondary peripheral
      chondrosarcoma, in relation to possible mutations and promoter methylation. The
      mutation status of patients with multiple osteochondromas correlated with
      decreased EXT1 or EXT2 expression found in their resected tumours. We could not
      show somatic point mutations or promoter hypermethylation in 17 solitary tumours;
      however, EXT1 expression was decreased in 15 cases, whereas EXT2 was not.
      Intracellular accumulation of syndecan-2 and heparan sulphate-bearing isoforms of
      CD44 (CD44v3) was found in most tumours, which concentrated in the Golgi
      apparatus as shown by confocal microscopy. This contrasted with the extracellular
      expression found in normal growth plates. In conclusion, mutational inactivation
      of either EXT1 or EXT2 leads to loss of mRNA expression of the corresponding
      gene. We hypothesize that loss of EXT expression disrupts the function of the
      EXT1/2 complex in HSPG biosynthesis, resulting in the intracellular accumulation
      of HSPG core proteins that we found in these tumours.

PMID- 17226761
TI  - CD36 is a novel and potential anti-fibrogenic target in albumin-induced renal
      proximal tubule fibrosis.
AB  - Albumin is not only a risk factor for diabetic nephropathy (DN), but also a
      therapeutic target. Hence, scientists have long sought ways to elucidate the
      interactions between albumin and diabetic renal tubule fibrosis. CD36, a surface
      receptor for thrombospondin-1, has been reported to interact with latent
      transforming growth factor-beta1 (TGF-beta1) and activate its fibrogenic
      bioactivity. This study elucidates the interactions between CD36 and renal tubule
      fibrosis. LLC-PK1 cells were applied to represent renal proximal tubule cells.
      The expression of CD36 was evaluated by flow cytometry. Fibronectin was assayed
      by Western blot and enzyme-linked immunosorbent assay (ELISA). Bioactive TGF
      beta1 was assayed by ELISA. We demonstrated that albumin was shown significantly
      to inhibit cell growth without affecting hypertrophy status since protein content
      and cell size remained unaffected under albumin treatment. Moreover, albumin dose
      dependently (0, 1, or 10 mg/ml) enhanced the secretion of bioactive TGF-beta1 and
      fibronectin with the upregulation of CD36. Intriguingly, CD36 siRNA, a potent
      silencer for CD36 effectively suppressed the albumin-induced increase in CD36,
      TGF-beta1, and even fibronectin level. Accordingly, albumin is a pro-fibrogenic
      factor for proximal tubule cells since albumin per se markedly upregulated the
      expression of TGF-beta1 and fibronectin. Most importantly, CD36 may mediate
      albumin-induced cellular fibrosis since CD36 siRNA appeared to have anti-fibrosis
      effects. This work suggests that CD36 is a novel and potential therapeutic target
      for diabetic renal tubule fibrosis.

PMID- 17226762
TI  - An oncogenetic tree model in gastrointestinal stromal tumours (GISTs) identifies
      different pathways of cytogenetic evolution with prognostic implications.
AB  - To model the cytogenetic evolution in gastrointestinal stromal tumour (GIST), an
      oncogenetic tree model was reconstructed using comparative genomic hybridization
      data from 203 primary GISTs (116 gastric and 87 intestinal GISTs, including 151
      newly analysed cases), with follow-up available in 173 cases (mean 40 months;
      maximum 133 months). The oncogenetic tree model identified three major
      cytogenetic pathways: one initiated by -14q, one by -1p, and another by -22q. The
      -14q pathway mainly characterized gastric tumours with predominantly stable
      karyotypes and more favourable clinical course. On the other hand, the -1p
      pathway was more characteristic of intestinal GISTs, with an increased capacity
      for cytogenetic complexity and more aggressive clinical course. Loss of 22q, more
      closely associated with -1p than -14q, appeared to initiate the critical
      transition to an unfavourable cytogenetic subpathway. This -22q pathway included
      accumulation of +8q, -9p, and -9q, which could all predict disease-free survival
      in addition to tumour site. Thus, insights into the cytogenetic evolution
      obtained from oncogenetic tree models may eventually help to gain a better
      understanding of the heterogeneous site-dependent biological behaviour of GISTs.

PMID- 17226763
TI  - Neuronal morphology and neuropil structure in the stomatogastric ganglion of the
      lobster, Homarus americanus.
AB  - The stomatogastric nervous system (STNS) has long been used as a model system for
      the study of central pattern generation, neuromodulation, and network dynamics.
      Anatomical studies of the crustacean stomatogastric ganglion (STG) in different
      species have mostly been restricted to subsets of neurons and/or general
      structural features. For the first time, we describe the morphology of all STG
      neurons belonging to the two circuits that produce the well-described pyloric and
      gastric rhythms in the lobster, Homarus americanus. Somata sit on the dorsal and
      lateral surface of the STG and send a single primary neurite into the core of the
      neuropil, which is mostly made up of larger lower order branches. The perimeter
      of the neuropil consists mostly of finer higher order branches.
      Immunohistochemical labeling for synaptic proteins is associated with the small
      diameter branches. Somata positions are not constant but show preferred locations
      across individuals. The number of copies is constant for all neuron types except
      the PY and GM neurons (PY neuron number ranges from 3 to 7, and GM neuron number
      ranges from 6 to 9). Branch structure is largely nondichotomous, and branches can
      deviate substantially from cylindrical shape. Diameter changes at branch points
      can be as large as 20-fold. Clearly, the morphology of a specific neuron type can
      be quite variable from animal to animal.

PMID- 17226764
TI  - Occipital sulci of the human brain: variability and probability maps.
AB  - The morphological variation of the sulci of the occipital region of the human
      brain was examined in both the left and the right hemispheres in 40 normal adult
      human brains on magnetic resonance images. We identified the occipital sulci and
      marked their corresponding gray matter voxels on the magnetic resonance images,
      which had been transformed into the Montreal Neurological Institute standard
      proportional stereotaxic space in order to construct probability maps. In the
      medial occipital region, the calcarine sulcus was the longest and most constant
      sulcus. We identified, in the inferior part of the medial occipital lobe, the
      lingual sulcus and the posterior collateral sulcus, and, in the superior part,
      the inferior and superior sagittal sulci of the cuneus. On the lateral surface of
      the occipital lobe, the lateral occipital, the lunate, and the transverse and
      inferior occipital sulci were identified. The parieto-occipital fissure and the
      temporo-occipital incisure were also identified on the lateral and medial
      surfaces. Finally, the patterns of the occipital sulci and gyri were examined in
      20 post-mortem human hemispheres fixed in formalin. Probability maps of the
      occipital sulci were constructed, which provide a quantitative description of the
      variability of the sulci in standard stereotaxic space and may be used to
      identify the location of voxels in other magnetic resonance images transformed
      into the same streotaxic space. These maps are a useful tool in the study of
      functional activations related to visual processing.

PMID- 17226765
TI  - Dual transcriptional control of claudin-11 via an overlapping GATA/NF-Y motif:
      positive regulation through the interaction of GATA, NF-YA, and CREB and negative
      regulation through the interaction of Smad, HDAC1, and mSin3A.
AB  - The expression of claudin-11, a key integral tight junction protein, is tightly
      regulated to ensure that the integrity of the seminiferous epithelium could be
      maintained during the translocation of spermatocytes at the blood-testis barrier
      at stages VIII-IX. In this study, we elucidate how the overlapping GATA/NF-Y
      motif within the core promoter of claudin-11 gene is modulated by differential
      binding of various transcription factors, resulting in dual transcriptional
      control. Using electrophoretic mobility shift assay (EMSA) and chromatin
      immunoprecipitation (ChIP) assay, we confirmed that GATA, nuclear factor YA (NF
      YA), and cAMP response element-binding protein (CREB) form a complex in vivo and
      bind to the GATA/NF-Y region to promote claudin-11 gene transcription. Such gene
      activations were significantly reduced in the presence of siRNA specific to these
      transcription factors. GATA and CREB transactivation could be further modulated
      by the presence of Smad3 and Smad4 proteins. Binding of Smad proteins at the
      GATA/NF-Y motif could repress the GATA and CREB transactivation of claudin-11
      gene. Such repression which required the recruitment and physical interactions of
      histone deacetylase 1 and its co-repressor, mSin3A with Smad proteins, was
      abolished by treatment with Trichostatin A, thus suggesting the involvement of
      histone deacetylation at the site of the promoter region. It is believed that
      cyclic changes in the ratio of positive regulators (GATA, NF-Y, and CREB) to
      negative regulators (Smads) in the seminiferous epithelium during the
      spermatogenic cycle might provide a precise control in claudin-11 gene
      transcription.

PMID- 17226766
TI  - Concerted activation of the Mdm2 promoter by p72 RNA helicase and the
      coactivators p300 and P/CAF.
AB  - A scarcely studied and under-recognized feature of RNA helicases is their ability
      to regulate gene transcription. In particular, very little is known about the
      role of p72 RNA helicase in gene regulation. Here, we have analyzed how this
      helicase may enhance promoter activity. We demonstrate that p72 RNA helicase
      forms complexes with the homologous coactivators p300 and CBP in vitro and in
      vivo, especially leading to an enhancement of the transactivation potential of
      their C-termini. In addition, we show that the p300/CBP-associated protein
      (P/CAF) also interacts with p72 RNA helicase, and both this interaction and the
      binding to p300/CBP are mediated by the N-terminal 63 amino acids of p72 RNA
      helicase. p300, P/CAF and p72 RNA helicase synergize to stimulate selected
      promoters, including the Mdm2 one. Notably, downregulation of p72 RNA helicase
      leads to reduced Mdm2 transcription. Furthermore, our data suggest that p72 RNA
      helicase activates the Mdm2 promoter in a p53 dependent and independent manner.
      Collectively, our results have unraveled a mechanism of how p72 RNA helicase can
      regulate gene transcription, namely by cooperating with p300/CBP and P/CAF.
      Thereby, p72 RNA helicase may not only be involved in the p53-Mdm2 regulatory
      loop, but also profoundly impact on the transcriptome through various CBP/p300
      and P/CAF interacting proteins.

PMID- 17226768
TI  - Oncostatin M promotes osteogenesis and suppresses adipogenic differentiation of
      human adipose tissue-derived mesenchymal stem cells.
AB  - Oncostatin M (OSM) is a multifunctional cytokine of the interleukin-6 family and
      has been implicated in embryonic development, differentiation, inflammation, and
      regeneration of liver and bone. In the present study, we demonstrated that
      treatment of human adipose mesenchymal stem cells (hADSCs) with OSM-attenuated
      adipogenic differentiation, as indicated by decreased accumulation of
      intracellular lipid droplets and down-regulated expression of adipocytic markers,
      such as lipoprotein lipase and PPARgamma. However, OSM treatment stimulated
      osteogenic differentiation, as demonstrated by the increase in matrix
      mineralization and expression levels of osteogenic differentiation markers,
      including alkaline phosphatase, Runx2, and osteocalcin. OSM treatment induced
      activation of JAK2, JAK3, and ERK in hADSCs, and pre-treatment of hADSCs with the
      JAK2 inhibitor, AG490, significantly restored the OSM-induced inhibition of
      adipogenic differentiation. Whereas, the JAK3 inhibitor, WHI-P131, and the MEK
      inhibitor, U0126, had no effects on the anti-adipogenic activity of OSM. On the
      other hand, the pro-osteogenic activity of OSM was prevented by treatment of the
      cells with WHI-P131 or U0126, but not with AG490. These results indicate that
      distinct signaling pathways, including JAK2, JAK3, and MEK-ERK, play specific
      roles in the OSM-induced anti-adipogenic and pro-osteogenic differentiation of
      hADSCs.

PMID- 17226769
TI  - NF-kappaB pathway is involved in griseofulvin-induced G2/M arrest and apoptosis
      in HL-60 cells.
AB  - Griseofulvin (GF), an oral antifungal agent, has been shown to exert
      antitumorigenesis effect through G2/M cell cycle arrest in colon cancer cells.
      But the underlying mechanisms remained obscure. The purpose of this study is to
      test the cytotoxic effect of GF on HL-60 and HT-29 cells and elucidate its
      underlying molecular pathways. Dose-dependent and time-course studies by flow
      cytometry demonstrated that 30 to 60 microM GF significantly induced G2/M arrest
      and to a less extend, apoptosis, in HL-60 cells. In contrast, only G2/M arrest
      was observed in HT-29 cells under similar condition. Pretreatment of 30 microM
      TPCK, a serine protease inhibitor, completely reversed GF-induced G2/M cell cycle
      arrest and apoptosis in HL-60 cells but not in HT-29 cells. The GF-induced G2/M
      arrest in HL-60 cells is reversible. Using EMSA and super-shift analysis, we
      demonstrated that GF stimulated NF-kappaB binding activity in HL-60 cells, which
      was completely inhibited by pretreatment of TPCK. Treatment of HL-60 with 30
      microM GF activated JNK but not ERK or p38 MAPK and subsequently resulted in
      phosphorylation of Bcl-2. Pretreatment of TPCK to HL-60 cells blocked the GF
      induced Bcl-2 phosphorylation but not JNK activation. Time course study
      demonstrated that activation of cdc-2 kinase activity by GF correlated with Bcl-2
      phosphorylation. Taken together, our results suggest that activation of NF-kappaB
      pathway with cdc-2 activation and phosphorylation of Bcl-2 might be involved in
      G2/M cell cycle arrest in HL-60 cells.

PMID- 17226767
TI  - Periostin regulates collagen fibrillogenesis and the biomechanical properties of
      connective tissues.
AB  - Periostin is predominantly expressed in collagen-rich fibrous connective tissues
      that are subjected to constant mechanical stresses including: heart valves,
      tendons, perichondrium, cornea, and the periodontal ligament (PDL). Based on
      these data we hypothesize that periostin can regulate collagen I fibrillogenesis
      and thereby affect the biomechanical properties of connective tissues.
      Immunoprecipitation and immunogold transmission electron microscopy experiments
      demonstrate that periostin is capable of directly interacting with collagen I. To
      analyze the potential role of periostin in collagen I fibrillogenesis, gene
      targeted mice were generated. Transmission electron microscopy and morphometric
      analyses demonstrated reduced collagen fibril diameters in skin dermis of
      periostin knockout mice, an indication of aberrant collagen I fibrillogenesis. In
      addition, differential scanning calorimetry (DSC) demonstrated a lower collagen
      denaturing temperature in periostin knockout mice, reflecting a reduced level of
      collagen cross-linking. Functional biomechanical properties of periostin null
      skin specimens and atrioventricular (AV) valve explant experiments provided
      direct evidence of the role that periostin plays in regulating the viscoelastic
      properties of connective tissues. Collectively, these data demonstrate for the
      first time that periostin can regulate collagen I fibrillogenesis and thereby
      serves as an important mediator of the biomechanical properties of fibrous
      connective tissues.

PMID- 17226770
TI  - Jedi--a novel transmembrane protein expressed in early hematopoietic cells.
AB  - Self-renewal and differentiation of hematopoietic stem and progenitor cells are
      defined by the ensembles of genes expressed by these cells. Here we report
      identification of a novel gene named Jedi, which is expressed predominantly in
      short- and long-term repopulating stem cells when compared to more mature bone
      marrow progenitors. Jedi mRNA encodes a transmembrane protein that contains
      multiple EGF-like repeats. Jedi and two earlier reported proteins, MEGF10 and
      MEGF11, share a substantial homology and are likely to represent a novel protein
      family. Studies of the potential role of Jedi in hematopoietic regulation
      demonstrated that the retrovirally mediated expression of Jedi in bone marrow
      cells decreased the number of myeloid progenitors in in vitro clonogenic assays.
      In addition, expression of Jedi in NIH 3T3 fibroblasts resulted in a decreased
      number of late and early myeloid progenitors in the non-adherent co-cultured bone
      marrow cells. Jedi shares a number of structural features with the
      Jagged/Serrate/Delta family of Notch ligands, and our experiments indicate that
      the extracellular domain of Jedi, similar to the corresponding domain of Jagged1,
      inhibits Notch signaling. On the basis of obtained results, we suggest that Jedi
      is involved in the fine regulation of the early stages of hematopoietic
      differentiation, presumably through the Notch signaling pathway.

PMID- 17226771
TI  - Dissection of mammalian replicators by a novel plasmid stability assay.
AB  - A plasmid, bearing a mammalian replication initiation region (IR) and a matrix
      attachment region (MAR) was previously shown to be efficiently amplified to high
      copy number in mammalian cells and to generate chromosomal homogeneously staining
      regions (HSRs). The amplification mechanism was suggested to entail a head-on
      collision at the MAR between the transcription machinery and the hypothetical
      replication fork arriving from the IR, leading to double strand breakage (DSB)
      that triggered HSR formation. The experiments described here show that such
      plasmids are stabilized if collisions involving not only promoter-driven
      transcription but also promoter-independent transcription are avoided, and stable
      plasmids appeared to persist as submicroscopic episomes. These findings suggest
      that the IR sequence that promotes HSR generation may correspond to the sequence
      that supports replication initiation (replicator). Thus, we developed a "plasmid
      stability assay" that sensitively detects the activity of HSR generation in a
      test sequence. The assay was used to dissect two replicator regions, derived from
      the c-myc and DHFR ori-beta loci. Consequently, minimum sequences that
      efficiently promoted HSR generation were identified. They included several
      sequence elements, most of which coincided with reported replicator elements.
      These data and this assay will benefit studies of replication initiation and
      applications that depend on plasmid amplification.

PMID- 17226773
TI  - Transcriptional regulation of human Oct4 by steroidogenic factor-1.
AB  - Oct4 encodes a transcription factor that is involved in the maintenance of self
      renewal in stem cells. Recently, the molecular mechanisms that regulate Oct4
      expression have come under investigation. In this study, we demonstrate that the
      orphan nuclear receptor steroidogenic factor-1 (SF-1) behaves as a
      transcriptional activator of human Oct4 (hOct4) through direct interaction with a
      SF-1 binding element in the hOct4 proximal promoter. We found that Oct4 and SF-1
      were co-expressed in undifferentiated human embryonal carcinoma NCCIT cells and
      downregulated during retinoic acid-mediated differentiation. We examined the
      functional role played by SF-1 in regulation of hOct4 transcription using a
      luciferase reporter assay and Western blot analysis. Overexpression of SF-1
      increased up to about threefold hOct4 promoter activity and endogenous hOct4
      protein expression. Sequence analysis of the hOct4 promoter revealed that the
      transcriptional activity was closely linked to Conserved Regions 1 (CR1) and 2
      (CR2), which contain three putative SF-1-binding sites (1st, 2nd, and 3rd SF-1).
      Binding assays and mutagenesis of binding sites indicated that the 1st and 2nd SF
      1 elements (in CR1 and CR2, respectively) might be important cis-regulatory
      elements in hOct4 promoter activity. However, differences in response to SF-1
      overexpression between wild-type and mutant hOct4 promoters revealed that the 1st
      SF-1 element is the key binding site for SF-1-mediated transcriptional
      activation. Thus, our data indicate that SF-1 plays a crucial role in the
      regulation of hOct4 transcription through direct binding to the 1st SF-1 in CR1
      of the hOct4 proximal promoter.

PMID- 17226772
TI  - Macrophage depletion in the murine olfactory epithelium leads to increased
      neuronal death and decreased neurogenesis.
AB  - Apoptosis of olfactory sensory neurons (OSNs) induced by olfactory bulbectomy
      (OBX) leads to the activation of resident macrophages within the olfactory
      epithelium (OE). These macrophages phagocytose degenerating OSNs and secrete
      chemokines, which recruit additional macrophages into the OE, and
      cytokines/growth factors, which regulate basal cell proliferation and
      differentiation and maturation of OSNs. In this study we apply for the first time
      the use of liposome-encapsulated clodronate to selectively deplete macrophages
      during the OSN degeneration/regeneration cycle in order to elucidate the role(s)
      of macrophages in regulating cellular mechanisms that lead to apoptosis and
      neurogenesis. Mice were injected intranasally and intravenously with either
      liposome-encapsulated clodronate or empty liposomes prior to and after OBX or
      sham OBX. At 48 hours after surgery the numbers of macrophages in the OE of both
      sham and OBX clodronate-treated mice were significantly reduced compared to
      liposome-treated controls (38% and 35%, respectively, P < 0.05). The reduction in
      macrophage numbers was accompanied by significant decreases in OE thickness (22%
      and 21%, P < 0.05), the number of mOSNs (1.2- and 1.9-fold, P < 0.05), and basal
      cell proliferation (7.6- and 3.8-fold, P < 0.005) in sham and OBX mice,
      respectively, compared to liposome-treated controls. In OBX mice there was also
      increased immunoreactivity for active caspase-3 in the OE and olfactory nerves of
      clodronate-treated OBX mice compared to liposome-treated controls. These results
      indicate that macrophages modulate the OSN population in the normal and target
      ablated murine OE by influencing neuronal survival and basal cell proliferation,
      resulting in neurogenesis and replacement of mature OSNs.

PMID- 17226774
TI  - Decorin synthesized by arterial smooth muscle cells is retained in fibrin gels
      and modulates fibrin contraction.
AB  - Fibrin serves as a provisional extracellular matrix (ECM) for arterial smooth
      muscle cells (ASMC) after vascular injury, yet little is known about the effect
      of fibrin on ECM remodeling by these cells. To address this question, monkey ASMC
      were grown on fibrin gels and tissue culture (TC) plastic, and proteoglycan
      synthesis and accumulation were assessed by radiolabeling. Initial rates of (35)S
      sulfate incorporation into proteoglycans were identical for both groups, but
      increased proteoglycan accumulation was observed in cultures grown for 48 h on
      fibrin. This increased accumulation on fibrin was due to reduced proteoglycan
      turnover and retention within the fibrin gel. Decorin and biglycan constituted 40
      and 14% of the total proteoglycan in the fibrin gels, whereas their combined
      contribution was only 12% in control matrices. To explore whether the retention
      of decorin in fibrin had any influence on the properties of the fibrin gel, ASMC
      mediated fibrin contraction assays were performed. Both de novo synthesis of
      decorin as well as decorin added during polymerization inhibited the ability of
      the cells to contract fibrin. In contrast, decorin added exogenously to mature
      fibrin matrices had no effect on fibrin gel contraction. This study illustrates
      that decorin derived from ASMC selectively accumulates in fibrin and modifies
      fibrin architecture and mechanical properties. Such an accumulation may influence
      wound healing and the thrombotic properties of this provisional pro
      atherosclerotic ECM.

PMID- 17226775
TI  - Interleukin-1beta selectively decreases the synthesis of versican by arterial
      smooth muscle cells.
AB  - Proteoglycans accumulate in lesions of atherosclerosis but little is known as to
      which factors regulate the synthesis of these molecules. Interleukin-1beta (IL
      1beta) is a cytokine involved in vascular lesion development but it is not clear
      whether it has specific effects on proteoglycan synthesis by arterial smooth
      muscle cells (ASMC). Monkey ASMC were treated with IL-1beta and proteoglycan
      synthesis assessed using [(35)S]-sulfate and [(35)S]-Trans amino acid labeling.
      Four prominent size populations of proteoglycans, as determined by SDS-PAGE
      gradient gel electrophoresis, were observed in the culture medium and identified
      as versican, biglycan, decorin, and an unknown population that migrated to the
      gel interface. IL-1beta treatment decreased significantly the synthesis of
      versican, while increasing the synthesis of decorin, but having no effect on
      biglycan synthesis. Northern blot analyses confirmed this selective effect on
      versican and decorin mRNA transcripts. Nuclear run-on and RNA inhibition studies
      showed that decreased mRNA for versican was due to increased mRNA degradation and
      not to changes in transcription. In addition, IL-1beta increased the synthesis of
      the population of proteoglycans that separated at the SDS-PAGE gel interface.
      Chondroitinase ABC lyase digestion of this population revealed a complex of
      proteins composed of versican (350 kDa), an unidentified protein (215 kDa), and a
      23 kDa protein identified by sequence analyses as serglycin. These data
      demonstrate that IL-1beta selectively downregulates versican synthesis by ASMC,
      while positively regulating the synthesis of other proteoglycans.

PMID- 17226776
TI  - Phosphorylation of mitochondrial phospholipid scramblase 3 by protein kinase C
      delta induces its activation and facilitates mitochondrial targeting of tBid.
AB  - Phospholipid scramblase 3 (PLS3) is a member of the phospholipid scramblase
      family present in mitochondria. PLS3 plays an important role in regulation of
      mitochondrial morphology, respiratory function, and apoptotic responses. PLS3 is
      phosphorylated by PKC-delta at Thr21 and is the mitochondrial target of PKC-delta
      induced apoptosis. Cells with overexpression of PLS3, but not the
      phosphoinhibitory mutant PLS3(T21A), are more susceptible to apoptosis induced by
      AD198, an extranuclear targeted anthracycline that activates PKC-delta. Here we
      report that the phosphomimetic mutant of PLS3(T21D) by itself can induce
      apoptosis in HeLa cells. Using proteoliposomes with addition of pyrene-labeled
      phosphatidylcholine (PC) at the outer leaflet, we measured the lipid flip-flop
      activity of PLS3 and its phosphorylation mutant. PLS3(T21D) is more potent than
      wild-type PLS3 or PLS3(T21A) to transfer pyrene-PC from the outer leaflet to the
      inner leaflet of liposomes. Based on our previous finding that PLS3 enhances tBid
      induced mitochondrial damages, we tested the hypothesis that PLS3 enhances
      cardiolipin translocation to mitochondrial surface and facilitates tBid
      targeting. Fluorescein-labeled tBid(G94E) was used as a probe to quantify
      cardiolipin on the surface of mitochondria. Mitochondria from cells treated with
      AD198 or cells expressing PLS3(T21D) had a higher level of tBid-binding capacity
      than control cells or cells expressing wild-type PLS3. These findings indicate
      that phosphorylation of PLS3 by PKC-delta induces PLS3 activation to facilitate
      mitochondrial targeting of tBid and apoptosis.

PMID- 17226777
TI  - Tumor microenvironment: the role of the tumor stroma in cancer.
AB  - The tumor microenvironment, composed of non-cancer cells and their stroma, has
      become recognized as a major factor influencing the growth of cancer. The
      microenvironment has been implicated in the regulation of cell growth,
      determining metastatic potential and possibly determining location of metastatic
      disease, and impacting the outcome of therapy. While the stromal cells are not
      malignant per se, their role in supporting cancer growth is so vital to the
      survival of the tumor that they have become an attractive target for
      chemotherapeutic agents. In this review, we will discuss the various cellular and
      molecular components of the stromal environment, their effects on cancer cell
      dynamics, and the rationale and implications of targeting this environment for
      control of cancer. Additionally, we will emphasize the role of the bone marrow
      derived cell in providing cells for the stroma.

PMID- 17226778
TI  - Identification and predominant expression of annexin A2 in epithelial-type cells
      of the rice field eel.
AB  - Annexin is the largest family of genes encoding eukaryotic calcium-binding
      proteins that do not contain the EF hand motif. Annexin A2 has a common annexin
      core domain, consisting of four so-called annexin repeats, and each of these
      repeats has about 70 amino acids in length. Here we report identification of
      annexin A2 from rice field eel by degenerate PCR and RACE techniques. Three
      dimensional structure prediction shows that it has similar annexin repeat
      architecture. Phylogenetic analysis shows that this gene fits with the annexin A2
      clade of vertebrates. Subcellular co-localization and co-immunoprecipitation
      indicated annexin A2 interacted with its ligand S100A10, confirming
      characteristics of the rice field eel annexin A2. RT-PCR and Western blot results
      indicate annexin A2 expressed ubiquitously in adult tissues. Immunofluorescence
      analysis shows obvious immunoreactivity in the nuclear membrane of developing
      oocytes and base membrane of mature oocytes in ovary and ovotestis. After the
      gonad differentiates into testis, annexin A2 protein expressed in the site of
      seminal vesicles epithelium in testis. The results provided a clue to the
      potential role of annexin A2 in the gonadal differentiation from ovary, via
      ovotestis to testis of the rice field eel.

PMID- 17226779
TI  - Crystallization and preliminary X-ray analysis of a domain in the Runx2
      transcription factor that interacts with the 1alpha,25 dihydroxy vitamin D3
      receptor.
AB  - The Runx2 transcription factor is a key regulator of osteoblast differentiation.
      In response to 1alpha,25 dihydroxy vitamin D3, Runx2 may interact with the
      1alpha,25 dihydroxy vitamin D3 receptor (VDR) in the promoter of target genes,
      producing a synergic activation of their transcription. Previous studies have
      suggested that the motifs responsible for the VDR-Runx2 interaction are contained
      within the 230-361 domain of Runx2. In this work, we confirmed by GST-pull down
      that Runx2(I(209-361)) is sufficient to interact with the VDR. To obtain
      structural information, GST-Runx2(I(209-361)) protein was overexpressed in
      Escherichia coli, purified and crystallized using the hanging-drop vapor
      diffusion method and polyethyleneglycol as a precipitant. The crystals were found
      to diffract to a maximum resolution of 2.7 A and a complete data set to a 3.3 A
      resolution was collected and analyzed. The crystals belong to the tetragonal
      system, with a space group P4 and unit-cell parameters of a = b = 90.8, and c =
      57.2 A. The presence of a monomer of the recombinant GST-Runx2(I(209-361)) in the
      asymmetric unit gives a V(M) of 2.7 A(3) Da(-1) and a solvent content of 54.8%.

PMID- 17226780
TI  - Evaluation of the viability of cultured corneal endothelial cells by quantitative
      electron probe X-ray microanalysis.
AB  - Construction of artificial organs and tissues by tissue engineering is strongly
      dependent on the availability of viable cells. For that reason, the viability and
      the physiological status of cells kept in culture must be evaluated before the
      cells can be used for clinical purposes. In this work, we determined the
      viability of isolated rabbit corneal endothelial cells by trypan blue staining
      and quantitative electron probe X-ray microanalysis. Our results showed that the
      ionic content of potassium in cultured corneal endothelial cells tended to rise
      initially, but significantly decreased in cells in the fifth (and final)
      subculture, especially in comparison to cells in the fourth subculture (P <
      0.001). However, the concentration of sulfur was higher in the fifth subculture
      than in the fourth subculture (P < 0.001), with a nonsignificant increase in
      sodium in the fifth subculture (P = 0.031). These data imply a remarkable
      decrease in the K/Na ratio from the fourth to the fifth subculture. Our
      microanalytical results, along with the morphological differences between cells
      in the last two subcultures, are compatible with an early phase of the
      preapoptotic process in the fifth subculture, and suggest that cells of the first
      four subcultures would be better candidates for tissue engineering.

PMID- 17226781
TI  - Contributions of pro-oxidant and anti-oxidant conditions to the actions of 24,25
      dihydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 on phosphate uptake in
      intestinal cells.
AB  - The steroid hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] rapidly stimulates the
      uptake of phosphate in isolated chick intestinal cells, while the steroid 24,25
      dihydroxyvitamin D3 [24,25(OH)2D3] inhibits the rapid stimulation by 1,25(OH)2D3.
      Earlier work in this laboratory has indicated that a cellular binding protein for
      24,25(OH)2D3 is the enzyme catalase. Since binding resulted in decreased catalase
      activity and increased H2O2 production, studies were undertaken to determine if
      pro-oxidant conditions mimicked the inhibitory actions of 24,25(OH)2D3, and anti
      oxidant conditions prevented the inhibitory actions of 24,25(OH)2D3. An antibody
      against the 24,25(OH)2D3 binding protein was found to neutralize the inhibitory
      effect of the steroid on 1,25(OH)2D3-mediated 32P uptake. Incubation of cells in
      the presence of 50 nM catalase was also found to alleviate inhibition. In another
      series of experiments, isolated intestinal epithelial cells were incubated as
      controls or with 1,25(OH)2D3, each in the presence of the catalase inhibitor 3
      amino-1,2,4-triazole, or with 1,25(OH)2D3 alone. Cells exposed to hormone alone
      again showed an increased accumulation of 32P, while cells treated with catalase
      inhibitor and hormone had uptake levels that were indistinguishable from
      controls. We tested whether inactivation of protein kinase C (PKC), the signaling
      pathway for 32P uptake, occurred. Incubation of cells with phorbol-13-myristate
      (PMA) increased 32P uptake, while cells pretreated with 50 microM H2O2 prior to
      PMA did not exhibit increased uptake. Likewise, PMA significantly increased PKC
      activity while cells exposed to H2O2 prior to PMA did not. It is concluded that
      catalase has a central role in mediating rapid responses to steroid hormones.

PMID- 17226782
TI  - Injury of skeletal muscle and specific cytokines induce the expression of gap
      junction channels in mouse dendritic cells.
AB  - Dendritic cells (DCs) in culture express at least connexin43, a protein subunit
      of gap junctions, and form gap junction channels, which could be important for T
      cells activation. Here, we evaluated whether DCs express connexins in vivo and
      also to identify components of their microenvironment that regulate the
      functional expression of gap junctions. In vivo studies were performed in lymph
      nodes of mice under control conditions or after skeletal muscle damage. In double
      immunolabeling studies, connexin45 was frequently detected in DEC205(+) DCs in
      lymph nodes of control animals, whereas connexin43 was rarely found in DCs.
      However, connexin43 was upregulated in DCs after skeletal muscle damage.
      Upregulation of connexin43 gene expression by tissue damage was also confirmed in
      mice carrying a beta-galactosidase reporter gene in a connexin43 allele. The
      effect of several cytokines on the expression of functional gap junctions between
      cultured DCs was also tested. Under control conditions, cultured DCs did not
      communicate via gap junctions. However, after treatment with keratinocyte
      conditioned medium or cytokine mixtures containing at least TNF-alpha and IL
      1beta, they became transiently coupled through a pathway sensitive to octanol, a
      gap junction blocker. Cellular coupling induced by effective cytokine mixtures
      was prevented by IL-6. Single cytokines (TNF-alpha, IL-1beta, IFN-gamma, or IL-6)
      or other mixtures than the described above did not induce coupling via gap
      junctions. Increased levels of connexin43 and connexin45 protein and mRNA
      accompanied the appearance of cellular coupling. These studies provide
      demonstration of connexin expression and regulation by specific danger signals in
      DCs.

PMID- 17226783
TI  - Beta-adrenergic receptor agonists delay while antagonists accelerate epithelial
      wound healing: evidence of an endogenous adrenergic network within the corneal
      epithelium.
AB  - Wound healing is a complex and well-orchestrated biological process. Corneal
      epithelial cells (CECs) must respond quickly to trauma to rapidly restore barrier
      function and protect the eye from noxious agents. They express a high level of
      beta2-adrenergic receptors but their function is unknown. Here, we report the
      novel finding that they form part of a regulatory network in the corneal
      epithelium, capable of modulating corneal epithelial wound repair. Beta
      adrenergic receptor agonists delay CEC migration via a protein phosphatase 2A
      mediated mechanism and decrease both electric field-directed migration and
      corneal wound healing. Conversely, beta-adrenergic receptor antagonists
      accelerate CEC migration, enhance electric field-mediated directional migration,
      and promote corneal wound repair. We demonstrate that CECs express key enzymes
      required for epinephrine (beta-adrenergic receptor agonist) synthesis in the
      cytoplasm and can detect epinephrine in cell extracts. We propose that the
      mechanism for the pro-motogenic effect of the beta-adrenergic antagonist is
      blockade of the beta2-adrenergic receptor preventing autocrine catecholamine
      binding. Further investigation of this network will improve our understanding of
      one of the most frequently prescribed class of drugs.

PMID- 17226784
TI  - Mutations of the RDX gene cause nonsyndromic hearing loss at the DFNB24 locus.
AB  - Ezrin, radixin, and moesin are paralogous proteins that make up the ERM family
      and function as cross-linkers between integral membrane proteins and actin
      filaments of the cytoskeleton. In the mouse, a null allele of Rdx encoding
      radixin is associated with hearing loss as a result of the degeneration of inner
      ear hair cells as well as with hyperbilirubinemia due to hepatocyte dysfunction.
      Two mutant alleles of RDX [c.1732G>A (p.D578N) and c.1404_1405insG
      (p.A469fsX487)] segregating in two consanguineous Pakistani families are
      associated with neurosensory hearing loss. Both of these mutant alleles are
      predicted to affect the actin-binding motif of radixin. Sequence analysis of RDX
      in the DNA samples from the original DFNB24 family revealed a c.463C>T transition
      substitution that is predicted to truncate the protein in the FERM domain (F for
      4.1, E for ezrin, R for radixin, and M for moesin) (p.Q155X). We also report a
      more complete gene and protein structure of RDX, including four additional exons
      and five new isoforms of RDX that are expressed in human retina and inner ear.
      Further, high-resolution confocal microscopy in mouse inner ear demonstrates that
      radixin is expressed along the length of stereocilia of hair cells from both the
      organ of Corti and the vestibular system.

PMID- 17226785
TI  - Heparin suppresses lipid raft-mediated signaling and ligand-independent EGF
      receptor activation.
AB  - Heparin is well known to suppress vascular smooth muscle cell (VSMC)
      proliferation, and attempts to exploit this therapeutically have led to
      recognition of multiple pathways for heparin's anti-mitogenic actions. At low
      concentrations (ca. 1 microg.ml(-1)), these suppressive effects may reflect
      physiological activities of endogenous heparan sulfates, and appear to be rapid
      responses to extracellular or cell surface-associated heparin. Because heparin
      has been shown to influence expression of caveolin proteins, and caveolae/lipid
      rafts are critical structures modulating cell signaling, we examined the effect
      of heparin on signaling involving cholesterol-rich membrane microdomains. The
      VSMC line PAC-1 activates the MAP kinase Erk in response to the cholesterol
      sequestering agents methyl-beta-cyclodextrin and nystatin. This follows a
      temporal sequence that involves Ras-GTP activation of MEK, and is independent of
      PKC, Src, and PI3 kinase. However, ligand-independent phosphorylation of the EGF
      receptor (EGFR) by removal of cholesterol precedes Ras activation, and the EGFR
      kinase inhibitor AG1478 blocks Erk phosphorylation, supporting occurrence of the
      signaling sequence EGFR-Ras-MEK-Erk. Phosphorylation of EGFR occurs predominantly
      in caveolin-rich microdomains as identified by Western blotting of fractions from
      density gradient centrifugation of membranes prepared under detergent-free
      conditions. In these situations, heparin inhibits phosphorylation of EGFR on the
      Src-dependent site Tyr(845), but not the autophosphorylation of Tyr(1173), and
      decreases Ras activation and Erk phosphorylation. We conclude that heparin can
      suppress Erk signaling in VSMC with effects on site-specific phosphorylation of
      EGFR localized in caveolin-enriched lipid rafts.

PMID- 17226786
TI  - Protein kinase D2 potentiates MEK/ERK/RSK signaling, c-Fos accumulation and DNA
      synthesis induced by bombesin in Swiss 3T3 cells.
AB  - Protein kinase D (PKD) plays an important role in mediating cellular DNA
      synthesis in response to G protein-coupled receptor (GPCR) agonists but the
      function of other isoforms of the PKD family has been much less explored. Here,
      we examined whether PKD2 overexpression in Swiss 3T3 cells facilitates DNA
      synthesis and the activation of the extracellular regulated protein kinase (ERK)
      pathway in response to the mitogenic GPCR agonist bombesin. We show that PKD2
      overexpression markedly potentiated the ability of this agonist to induce DNA
      synthesis. Addition of bombesin to Swiss 3T3 cells overexpressing PKD2 also
      induced a striking increase in the duration of MEK/ERK/RSK activation as compared
      with cultures of control cells. In contrast, neither DNA synthesis nor the
      duration of ERK activation in response to epidermal growth factor, which acts via
      protein kinase C/PKD2-independent pathways, was increased. Furthermore, bombesin
      promoted a striking accumulation of c-Fos protein in cells overexpressing PKD2.
      Our study demonstrates that PKD2, like PKD, facilitates mitogenesis and supports
      the hypothesis that an increase in the duration of the ERK signaling leading to
      accumulation of immediate gene products is one of the mechanisms by which
      isoforms of the PKD family enhance re-initiation of DNA synthesis by Gq-coupled
      receptor activation.

PMID- 17226787
TI  - Fractionated and acute irradiation induced signaling in a murine tumor.
AB  - The effect of fractionated doses of Co(60) gamma-irradiation (2 Gy per fraction
      over 5 days), as is delivered in cancer radiotherapy, was compared with acute
      doses of 10 and 2 Gy, in a serially transplanted mouse fibrosarcoma grown in
      Swiss mice. The aspects that were studied included the three major mitogen
      activated protein (MAP) kinases, namely p44 MAP kinase, p38 MAP kinase, and
      stress-activated protein (SAP) kinase, which are known to be involved in
      determining the cell fate following exposure to ionizing radiation. The response
      of dual specificity phosphatase PAC1 which is involved in the dephosphorylation
      of MAP kinases was also looked at. There were significant differences in the
      response to different dose regimens for all the factors studied. Fractionated
      irradiation elicited an adaptive response with a sustained activation over 7 days
      of prosurvival p44 MAP kinase which was balanced by the increased activation of
      proapoptotic p54 SAP kinase up to 1 day post-irradiation, whereas, phosphorylated
      p38 MAP kinase showed a decrease at most time points. PAC1 was induced following
      fractionated irradiation and may be acting as a feed back regulator of p44 MAP
      kinase. The activation of SAP kinase after fractionated irradiation may be a
      stress response, whereas, constitutively activated p44 MAP kinase may play an
      important role in the induction of radioresistance during fractionated
      radiotherapy of cancer and may serve as a promising target for specific
      inhibitors to enhance the efficacy of radiotherapy.

PMID- 17226788
TI  - From the laboratory bench to the patient's bedside: an update on clinical trials
      with mesenchymal stem cells.
AB  - Mesenchymal Stem Cells (MSCs) are non-hematopoietic multi-potent stem-like cells
      that are capable of differentiating into both mesenchymal and non-mesenchymal
      lineages. In fact, in addition to bone, cartilage, fat, and myoblasts, it has
      been demonstrated that MSCs are capable of differentiating into neurons and
      astrocytes in vitro and in vivo. MSCs are of interest because they are isolated
      from a small aspirate of bone marrow and can be easily expanded in vitro. As
      such, these cells are currently being tested for their potential use in cell and
      gene therapy for a number of human diseases. Nevertheless, there are still some
      open questions about origin, multipotentiality, and anatomical localization of
      MSCs. In this review, we discuss clinical trials based on the use of MSCs in
      cardiovascular diseases, such as treatment of acute myocardial infarction,
      endstage ischemic heart disease, or prevention of vascular restenosis through
      stem cell-mediated injury repair. We analyze data from clinical trials for
      treatment of osteogenesis imperfecta (OI), which is a genetic disease
      characterized by production of defective type I collagen. We describe progress
      for neurological disease treatment with MSC transplants. We discuss data on
      amyotrophic lateral sclerosis (ALS) and on lysosomal storage diseases (Hurler
      syndrome and metachromatic leukodystrophy). A section of review is dedicated to
      ongoing clinical trials, involving MSCs in treatment of steroid refractory Graft
      Versus Host Disease (GVHD); periodontitis, which is a chronic disease affecting
      periodontium and causing destruction of attachment apparatus, heart failure, and
      bone fractures. Finally, we will provide information about biotech companies
      developing MSC therapy.

PMID- 17226790
TI  - Descending GABAergic projections to the mesencephalic locomotor region in the
      lamprey Petromyzon marinus.
AB  - The mesencephalic locomotor region (MLR) plays a significant role in the control
      of locomotion in all vertebrate species investigated. Forebrain neurons are
      likely to modulate MLR activity, but little is known about their inputs.
      Descending GABAergic projections to the MLR were identified by double-labeling
      neurons using Neurobiotin injected into the MLR combined with immunofluorescence
      against GABA. Several GABAergic projections to the MLR were identified in the
      telencephalon and diencephalon. The most abundant GABAergic projection to the MLR
      came from the caudal portion of the medial pallium, a region that may have
      similarities with the amygdala of higher vertebrates. A small population of
      GABAergic cells projecting to the MLR was found in the striatum and the ventral
      portion of the lateral pallium, which could respectively correspond to the input
      and output components of the basal ganglia thought to be involved in the
      selection of motor programs. Other GABAergic projections were found to come from
      the thalamus and the hypothalamus, which could take part in the motivational
      aspect of motor behavior in lampreys. Electrophysiological experiments were also
      carried out to examine the effects of GABA agonists and antagonists injected into
      the MLR in a semi-intact lamprey preparation. The GABA agonist inhibited
      locomotion, whereas the GABA antagonist initiated it. These results suggest that
      the GABAergic projections to the MLR modulate the activity of MLR neurons, which
      would be inhibited by GABA at rest.

PMID- 17226789
TI  - Generation of insulin-producing cells from PDX-1 gene-modified human mesenchymal
      stem cells.
AB  - Islet cell replacement is considered as the optimal treatment for type I
      diabetes. However, the availability of human pancreatic islets for
      transplantation is limited. Here, we show that human bone marrow-derived
      mesenchymal stem cells (hMSCs) could be induced to differentiate into functional
      insulin-producing cells by introduction of the pancreatic duodenal homeobox-1
      (PDX-1). Recombinant adenoviral vector was used to deliver PDX-1 gene into hMSCs.
      After being infected with Ad-PDX-1, hMSCs were successfully induced to
      differentiate into insulin-secreting cells. The differentiated PDX-1+ hMSCs
      expressed multiple islet-cell genes including neurogenin3 (Ngn3), insulin, GK,
      Glut2, and glucagon, produced and released insulin/C-peptide in a weak glucose
      regulated manner. After the differentiated PDX-1+ hMSCs were transplanted into
      STZ-induced diabetic mice, euglycemia can be obtained within 2 weeks and
      maintained for at least 42 days. These findings validate the hMSCs model system
      as a potential basis for enrichment of human beta cells or their precursors, and
      a possible source for cell replacement therapy in diabetes.

PMID- 17226791
TI  - Regulation of matrix metalloproteinases and tissue inhibitors of matrix
      metalloproteinases by Porphyromonas gingivalis in an engineered human oral mucosa
      model.
AB  - Under physiological conditions, matrix metalloproteinases (MMPs) are involved in
      the remodeling and turnover of periodontal tissue and their activity is tightly
      regulated by tissue inhibitors of metalloproteinases (TIMPs). Disturbances in the
      balance between MMPs and TIMPs may result in excessive tissue destruction. We
      previously used an engineered human oral mucosa (EHOM) model to demonstrate that
      Porphyromonas gingivalis, a major etiological agent of periodontitis, infiltrates
      connective tissue and induces significant loss of attachment of the stratified
      epithelium from the basement membrane. The aim of the present study was to
      investigate the effect of P. gingivalis on the expression and production of MMP
      2, MMP-9, TIMP-1, and TIMP-2 by oral fibroblasts and epithelial cells. The EHOM
      model was infected with P. gingivalis ATCC 33277 or its derivative gingipain-null
      mutant (KDP128) for different periods of time. MMP and TIMP mRNA expression was
      evaluated by reverse transcription-polymerase chain reaction (RT-PCR) analysis,
      while protein secretion into the culture medium was assessed by enzyme-linked
      immunosorbent assays. P. gingivalis significantly up-regulated MMP-2 and MMP-9
      mRNA expression by oral epithelial cells. This MMP gene activation was paralleled
      by TIMP-2 gene activation. However, only MMP-9 mRNA expression was significantly
      enhanced by the gingipain-null mutant. At 8 and 24 h post-infection, P.
      gingivalis increased significantly the MMP-9 protein level compared to the
      uninfected EHOM model. The present study reports the ability of P. gingivalis to
      regulate MMP and TIMP production by oral cells, a phenomenon that may contribute
      to tissue destruction.

PMID- 17226793
TI  - Out of the veil of death rode the one million! Neandertals and their genes.
AB  - Two recent papers report extensive nuclear DNA sequence from a 38,000-year-old
      Neandertal fossil, comparing it to modern humans and estimating when it diverged
      from, and whether it contributed to, our gene pool. Based on 65,250 and over a
      million base-pairs of sequence across the genome, respectively, the groups
      arrived at slightly different interpretations. The data are an exciting and
      interesting new contribution, but are not surprising, and a sense of history and
      question helps put them in perspective.

PMID- 17226792
TI  - The phosphodiesterase 5 inhibitor sildenafil stimulates angiogenesis through a
      protein kinase G/MAPK pathway.
AB  - cGMP-degrading pathways have received little attention in the context of
      angiogenesis. In the present study we set out to determine whether cGMP-specific
      phosphodiesterase 5 (PDE5) inhibition affects new blood vessel growth. Incubation
      of chicken chorioallantoic membranes (CAMs) in vivo with sildenafil increased
      vascular length in a dose-dependent manner. Moreover, incubation of cultured
      endothelial cells (ECs) with the PDE5 inhibitor promoted proliferation,
      migration, and organization into tube-like structures. The effects of sildenafil
      on the angiogenesis-related properties of EC could be blocked by pre-treatment
      with the soluble guanylyl cyclase (sGC) inhibitor ODQ or the protein kinase G
      (PKG) I inhibitor DT-3. In addition, over-expression of sGC in EC led to an
      enhanced growth and migratory response to sildenafil. To study the signaling
      pathways implicated in the sildenafil-stimulated angiogenic responses we
      determined the phosphorylation status of mitogen-activated protein kinase (MAPK)
      members. Incubation of cells with sildenafil increased both extracellular signal
      regulated kinase 1/2 (ERK1/2) and p38 phosphorylation in a time-dependent manner.
      Inhibition of MEK by PD98059 and p38 with SB203580 blocked sildenafil-induced
      proliferation and migration, respectively, suggesting that these MAPK members are
      downstream of PDE5 and mediate the angiogenic effects of sildenafil. PDE5
      inhibitors could, thus, be used in disease states where neo-vessel growth is
      desired.

PMID- 17226794
TI  - Diurnal rhythm of the chromatin protein Hmgb1 in rat photoreceptors is under
      circadian regulation.
AB  - Hmgb1 belongs to a family of structure-specific DNA binding proteins with DNA
      chaperone-like properties that mediate chromatin remodeling in a wide range of
      nuclear processes including regulation of transcription, DNA repair, genome
      stability, and stress response. A diurnal oscillation of Hmgb1 at the protein
      level occurs in rat retinal photoreceptor cells and to a lesser extent in bipolar
      neurons. Expression of Hmgb1 was least at night at Zeitgeber time (ZT) 18 and
      maximal in the middle of the lights-on period (ZT6). Since rhythmic expression of
      Hmgb1 protein in photoreceptors continued in complete darkness, it is likely
      under control of a circadian clock. Within photoreceptor nuclei, Hmgb1
      colocalized with acetylated histone H3, a marker of euchromatin. Outside the
      nucleus a distinct smaller-sized isoform of Hmgb1 was present in photoreceptor
      inner segments and bound to a membrane fraction with characteristics of
      endoplasmic reticulum membranes. The rhythmic expression of Hmgb1 protein may
      underlie the circadian change in chromatin remodeling in addition to histone
      acetylation.

PMID- 17226795
TI  - Spam and the evolution of the fly's eye.
AB  - The open rhabdoms of the fly's eye enhance absolute sensitivity but to avoid
      compromising spatial acuity they require precise optical geometry and neural
      connections.1 This neural superposition system evolved from the ancestral insect
      eye, which has fused rhabdoms. A recent paper by Zelhof and co-workers shows that
      the Drosophila gene spacemaker (spam) is necessary for development of open
      rhabdoms, and suggests that mutants revert to an ancestral state. Here I outline
      how open rhabdoms and neural superposition may have evolved via nocturnal
      intermediates, and discuss the implications for the role of spam in insect
      phylogeny.

PMID- 17226796
TI  - CAG and CTG repeat polymorphism in exons of human genes shows distinct features
      at the expandable loci.
AB  - Although the trinucleotide repeats are present in the exons of numerous human
      genes, the allele distribution is not well known, and the factors responsible for
      their intergenic and intragenic variability are not well understood. We have
      analyzed the length and sequence variation within the most commonly occurring CAG
      and CTG repeats in a large number of human genes selected to contain the longest
      reported repeat tracts. Our study revealed that in genes other than those
      implicated in the Triplet Repeat Expansion Diseases (TREDs), the very long and
      highly polymorphic repeats are rather infrequent. The length of pure repeat tract
      in the most frequent allele was found to correlate well with the rate of the
      repeat length polymorphism, and CAA triplets were shown to be the most frequent
      CAG repeat interruptions. As both the CAG and CAA triplets code for glutamine,
      our results may suggest that the selective pressure disfavors the long
      uninterrupted CAG repeats in genes and transcripts but not the long normal
      polyglutamine tracts in proteins. This may indicate that hairpin structures
      formed in ssDNA and RNA by long pure CAG repeats would be selected against as
      they may impede normal cellular processes.

PMID- 17226797
TI  - Aldosterone-sensitive neurons of the nucleus of the solitary tract: multisynaptic
      pathway to the nucleus accumbens.
AB  - The nucleus accumbens (NAc) is part of a forebrain system implicated in reward,
      motivation, and learning. NAc neurons become activated during various ingestive
      activities, including salt intake. A subset of neurons within the nucleus tractus
      solitarius (NTS) shows c-Fos activation during prolonged sodium deprivation in
      rats. These neurons express mineralocorticoid receptors and the enzyme 11-beta
      hydroxysteroid dehydrogenase type 2 (HSD2), which makes them selectively
      sensitive to aldosterone-an adrenal hormone that modulates sodium appetite. Here
      we tested whether these neurons project multisynaptically to the core or shell
      subregions of the NAc. Pseudorabies virus (PRV)-a retrograde transneuronal tracer
      was injected into the NAc in rats and after 3-4 days PRV-infected HSD2 neurons
      were identified. PRV injections into the NAc core yielded greater numbers of PRV
      labeled HSD2 neurons than did comparable injections into the NAc shell.
      Transneuronal labeling was also found in brainstem sites that receive direct
      projections from HSD2 neurons, namely, lateral parabrachial and prelocus
      coeruleus nuclei. In other experiments a retrograde neural tracer (cholera toxin
      beta-subunit) was injected into the NAc. Extensive retrograde labeling was found
      in the midline thalamus and frontal cortical regions, but no cells were labeled
      in the NTS or parabrachial region. These findings indicate that the HSD2 neurons
      project via a multisynaptic pathway to the NAc, which may be relayed sequentially
      through two sites: the dorsolateral pons and the paraventricular thalamic
      nucleus. HSD2 neurons may be part of an ascending pathway involved in the salt
      seeking behavior of sodium-depleted rats.

PMID- 17226798
TI  - Association of the neuronal nicotinic receptor beta2 subunit gene (CHRNB2) with
      subjective responses to alcohol and nicotine.
AB  - Nicotine addiction and alcohol dependence are highly comorbid disorders that are
      likely to share overlapping genetic components. We have examined two neuronal
      nicotinic receptor subunit genes (CHRNA4 and CHRNB2) for possible associations
      with nicotine and alcohol phenotypes, including measures of frequency of use and
      measures of initial subjective response in the period shortly after first using
      the drugs. The subjects were 1,068 ethnically diverse young adults participating
      in ongoing longitudinal studies of adolescent drug behaviors at the University of
      Colorado, representing both clinical and community samples. Analysis of six SNPs
      in the CHRNA4 gene provided modest support for an association with past 6 month
      use of alcohol in Caucasians (three SNPs with P < 0.08), but no evidence for an
      association with tobacco and CHRNA4 was detected. However, a SNP (rs2072658)
      located immediately upstream of CHRNB2 was associated with the initial subjective
      response to both alcohol and tobacco. This study provides the first evidence for
      association between the CHRNB2 gene and nicotine- and alcohol-related phenotypes,
      and suggests that polymorphisms in CHRNB2 may be important in mediating early
      responses to nicotine and alcohol.

PMID- 17226799
TI  - BDNF variant linked to anxiety-related behaviors.
AB  - Brain-derived neurotrophic factor (BDNF) is the most-abundant neurotrophin in the
      brain. In mammals, it is synthesized as a precursor called proBDNF, which is
      proteolytically cleaved to generate mature BDNF. The BDNF gene is located on
      chromosome 11p13, and a functional single nucleotide polymorphism (SNP) of this
      gene has been shown to produce a valine (Val)-to-methionine (Met) substitution in
      the proBDNF protein at codon 66 (Val66Met). Several papers suggest that this SNP
      is related to decreased hippocampal volume and hippocampus-mediated memory
      performance in humans. Recently, Chen et al. generated a variant BDNF mouse
      (BDNF(Met/Met)) that reproduces the phenotypic hallmarks in humans with a variant
      Met allele. In the behavioral analysis, BDNF(Met/Met) mice show increased anxiety
      related behaviors. This mini-review examines the impact of Met substitution of
      proBDNF on anxiety-related behaviors.

PMID- 17226801
TI  - Regulation of male traits by testosterone: implications for the evolution of
      vertebrate life histories.
AB  - The negative co-variation of life-history traits such as fecundity and lifespan
      across species suggests the existence of ubiquitous trade-offs. Mechanistically,
      trade-offs result from the need to differentially allocate limited resources to
      traits like reproduction versus self-maintenance, with selection favoring the
      evolution of optimal allocation mechanism. Here I discuss the physiological
      (endocrine) mechanisms that underlie optimal allocation rules and how such rules
      evolve. The hormone testosterone may mediate life-history trade-offs due to its
      pleiotropic actions in male vertebrates. Conservation in the actions of
      testosterone in vertebrates has prompted the 'evolutionary constraint
      hypothesis,' which assumes that testosterone signaling mechanisms and male traits
      evolve as a unit. This hypothesis implies that the actions of testosterone are
      similar across sexes and species, and only the levels of circulating testosterone
      concentrations change during evolution. In contrast, the 'evolutionary potential
      hypothesis' proposes that testosterone signaling mechanisms and male traits
      evolve independently. In the latter scenario, the linkage between hormone and
      traits itself can be shaped by selection, leading to variation in trade-off
      functions. I will review recent case studies supporting the evolutionary
      potential hypothesis and suggest micro-evolutionary experiments to unravel the
      mechanistic basis of life-history evolution.

PMID- 17226802
TI  - Non-genomic transgenerational inheritance of disease risk.
AB  - That there is a heritable or familial component of susceptibility to chronic non
      communicable diseases such as type 2 diabetes, obesity and cardiovascular disease
      is well established, but there is increasing evidence that some elements of such
      heritability are transmitted non-genomically and that the processes whereby
      environmental influences act during early development to shape disease risk in
      later life can have effects beyond a single generation. Such heritability may
      operate through epigenetic mechanisms involving regulation of either imprinted or
      non-imprinted genes but also through broader mechanisms related to parental
      physiology or behaviour. We review evidence and potential mechanisms for non
      genomic transgenerational inheritance of 'lifestyle' disease and propose that the
      'developmental origins of disease' phenomenon is a maladaptive consequence of an
      ancestral mechanism of developmental plasticity that may have had adaptive value
      in the evolution of generalist species such as Homo sapiens.

PMID- 17226800
TI  - Planar cell polarity signaling in vertebrates.
AB  - Planar cell polarity (PCP) refers to the polarization of a field of cells within
      the plane of a cell sheet. This form of polarization is required for diverse
      cellular processes in vertebrates, including convergent extension (CE), the
      establishment of PCP in epithelial tissues and ciliogenesis. Perhaps the most
      distinct example of vertebrate PCP is the uniform orientation of stereociliary
      bundles at the apices of sensory hair cells in the mammalian auditory sensory
      organ. The establishment of PCP in the mammalian cochlea occurs concurrently with
      CE in this ciliated epithelium, therefore linking three cellular processes
      regulated by the vertebrate PCP pathway in the same tissue and emerging as a
      model system for dissecting PCP signaling. This review summarizes the
      morphogenesis of this model system to assist the interpretation of the emerging
      data and proposes molecular mechanisms underlying PCP signaling in vertebrates.

PMID- 17226803
TI  - Physiological relevance of telomeric G-quadruplex formation: a potential drug
      target.
AB  - The concept of a G-quartet, a unique structural arrangement intrinsic to guanine
      rich DNA, was first introduced by Gellert and colleagues over 40 years ago. For
      decades, it has been uncertain whether the G-quartet and the structure that it
      gives rise to, the G-quadruplex, are purely in vitro phenomena. Nevertheless, the
      presence of signature G-rich motifs in the eukaryotic genome, and the plethora of
      proteins that bind to, modify or resolve this nucleic acid structure in vitro
      have provided circumstantial evidence for its physiological relevance. More
      recently, direct visualisation of G-quadruplex DNA at native telomeres was
      achieved, bolstering the evidence for its existence in the cell. Furthermore, G
      quadruplex folded telomeric DNA has been found to perturb telomere function and
      to impede the action of telomerase, an enzyme overexpressed in >85% of human
      cancers, hence opening up a novel avenue for cancer therapy in the form of G
      quadruplex stabilising agents.

PMID- 17226804
TI  - Development and function of the mammalian spleen.
AB  - The vertebrate spleen has important functions in immunity and haematopoiesis,
      many of which have been well studied. In contrast, we know much less about the
      mechanisms governing its early embryonic development. However, as a result of
      work over the past decade-mostly using knockout mice--significant progress has
      been made in unravelling the genetic processes governing the spleen's early
      development. Key genetic regulators, such as Tlx1 and Pbx1, have been identified,
      and we know some of the early transcriptional hierarchies that control the early
      patterning and proliferation of the splenic primordium. In mouse and humans,
      asplenia can arise as a result of laterality defects, or the spleen can be absent
      with no other discernible abnormalities. Surprisingly, given the spleen's diverse
      functions, asplenic individuals suffer no major haematopoietic or immune defects
      apart from a susceptibility to infection with encapsulated bacteria. Recent
      evidence has shed light on a previously unknown role of the spleen in the
      development and maintenance of specific B cell populations that are involved in
      the initial response to infection caused by encapsulated bacteria. The lack of
      these populations in asplenic mice and humans may go some way to explaining this
      susceptibility.

PMID- 17226805
TI  - The correlation of extranodal invasion with other prognostic parameters in lymph
      node positive breast cancer.
AB  - BACKGROUND: The presence of extranodal invasion (ENI) in the metastatic lymph
      nodes is reported to increase the risk of locoregional recurrence while
      shortening disease-free and overall survival in patients with breast cancer. In
      this study the relationship between ENI and other prognostic parameters and
      survival is investigated. METHODS: Of 650 patients with breast cancer who were
      treated in Ankara Oncology Teaching and Research Hospital from 1996 to 2003, 368
      (56.6%) had lymph node metastasis. The patients with axillary metastasis were
      separated into two groups as with and without invasion to lymph node capsule and
      the surrounding adipose tissue. Clinicopathologic features were analyzed by
      univariate and multivariate logistic regression. RESULTS: Of 368 patients with
      axillary metastasis, 135 (36.7%) had ENI. Based on multivariate analysis; the
      number of metastatic lymph nodes, lymphatic invasion, and tumor necrosis were
      found to be related with ENI. In the group with ENI, 5-year overall survival rate
      was 74.8%, compared to 82.3% for patients without ENI which was significantly
      lower (P = 0.04). CONCLUSIONS: In lymph node positive breast cancer with presence
      of ENI, adverse prognostic parameters are more frequently encountered and has a
      worse overall survival compared to group without ENI.

PMID- 17226807
TI  - Control of crystallinity of hydrated products in a calcium phosphate bone cement.
AB  - In this study, a calcium phosphate cement (CPC), consisting of partially
      crystallized calcium phosphate (PCCP), was synthesized. X-ray diffraction (XRD),
      Fourier transform infrared spectrometry (FTIR) and scanning electronic microscope
      (SEM) were used to characterize the cement. The results showed that by changing
      the ratio of amorphous calcium phosphate (ACP) to PCCP in the cement, hydrated
      products of controllable crystallinity were obtained. With increase in the
      relative amount of PCCP, the hydrated products changed gradually from very poor
      crystallinity with little needle-like hydroxyapatite (Hap) crystallites to
      relatively high crystallinity with more needle-like Hap crystallites; the
      compressive strength of the cement increased, and the degradation of the cement
      decreased. The cement was implanted into the tibia tubercle of healthy mature
      Zelanian white rabbits and the histological specimens were obtained after 4 and
      16 weeks of implantation. The result revealed that this bone cement was
      biocompatible and showed very early osteoconductive properties. Thus, the CPC has
      potential for use in orthopedic surgery for filling non- load-bearing bone
      defects.

PMID- 17226808
TI  - Dual radiolabeling to study protein adsorption competition in relation with
      hemocompatibility.
AB  - Human fibrinogen (Fg) and albumin (HSA) were labeled with (3)H and (14)C,
      respectively. Dual counting allowed the adsorbed amount of the two proteins to be
      determined simultaneously. Single adsorption, adsorption of the two proteins in
      competition, but also exchange (substitution by molecules of the same nature) and
      displacement (desorption under the action of the other protein) experiments were
      performed on two model surfaces, glass and polystyrene (PS), as well as on pure
      polyvinylchloride (PVC-s) and on PVC from blood bag (PVC-b). As expected, the
      adsorbed amount of a single protein is higher on a hydrophobic compared to a
      hydrophilic surface. When the two proteins are adsorbed in competition, they are
      found in equal proportion on glass, while HSA is twice more abundant than Fg on
      PS and PVC-s and about six times more abundant on PVC-b. This trend is related to
      an increase of the water contact angle of the substrates. For PVC-b, the contact
      angle is affected by the presence of aliphatic components exposed at the extreme
      surface, as determined by angle-resolved X-ray photoelectron spectroscopy. In
      exchange and displacement experiments, the first adsorbed molecules remain
      dominating on PS while they can be removed from glass. Given the known importance
      of HSA and Fg adsorption for the fate of materials placed in contact with blood,
      the method described in this paper may be used as a first approach to orient the
      design of surfaces with improved hemocompatibility.

PMID- 17226806
TI  - Bone tissue engineering with novel rhBMP2-PLLA composite scaffolds.
AB  - The aims of the present study were to fabricate a novel porous polylactic acid
      (PLLA) composite scaffold and evaluate the capacity of the scaffold in carrying
      recombinant bone morphogenetic protein 2 (rhBMP2) for engineering bone formation.
      The structures of the PLLA scaffolds were evaluated by SEM and the controlled
      release of rhBMP2 from the composite scaffolds was assayed by ELISA. Bone
      induction by the scaffolds loaded with or without rhBMP2 was performed in the
      calf muscle of twenty Wistar rats for 3, 7, 10, 14, and 28 days. Tissue specimens
      were examined by Masson's trichrome and von Kossa stainings, and
      immunohistochemistry of bone proteins. Our results indicated that a moderate
      foreign body reaction was found in control scaffolds, which lasted for 4 weeks.
      The addition of rhBMP2 to this novel scaffold dramatically alleviated the adverse
      responses to PLLA. Enhanced deposition of collagen matrix and endochondral
      formation were observed in rhBMP2-PLLA scaffolds at 7-10 days, compatible with an
      early release of rhBMP2 in the composite scaffolds. Bone sialoprotein and
      osteopontin were demonstrated simultaneously. Von Kossa staining was observed in
      the test group at 10-14 days. In conclusion, the PLLA scaffolds exhibited the
      capability of carrying rhBMP2 for inducing bone formation within 2 weeks. These
      results suggest that rhBMP2-PLLA scaffold may be applicable in tissue
      engineering.

PMID- 17226809
TI  - Retropubic versus perineal radical prostatectomy in early prostate cancer: eight
      year experience.
AB  - BACKGROUND: Prostate cancer is the most common malignancy in men and the second
      leading cause of cancer death. A randomized study was performed on patients with
      localized prostate cancer and treated with radical prostatectomy using the
      perineal or the retropubic approach comparing oncological outcomes, cancer
      control, and functional results. STUDY DESIGN: Between 1997 and 2004, in a
      randomized study 200 patients underwent a radical prostatectomy performed by
      retropubic (100 patients) or perineal (100 patients) approach. RESULTS:
      Differences between hospital stay, duration of catheter drainage, intraoperative
      blood loss, and transfusion requirements were statistically significant in favor
      of perineal prostatectomy. Differences between positive surgical margins and
      urinary continence in the two groups were not statistically significant at 6 and
      24 months. Differences between erectile function at 24 months were statistically
      significant in favor of retropubic prostatectomy. CONCLUSIONS: Radical perineal
      prostatectomy is an excellent alternative approach for radical surgery in the
      treatment of early prostate cancer.

PMID- 17226810
TI  - Shape-engineered fibroblasts: cell elasticity and actin cytoskeletal features
      characterized by fluorescence and atomic force microscopy.
AB  - The regulation of cell shape, which determines cell behaviors including adhesion,
      spreading, migration, and proliferation in an engineered artificial extracellular
      milieu, is an important task in tissue engineering and in development of
      functional biomaterials. To deepen the understandings of shape-dependent cell
      mechanics, the cell elasticity and structural features of the actin cytoskeleton
      (CSK) were characterized for shape-engineered fibroblasts; round and spindle
      shaped cells cultured on photolithographically microprocessed surfaces, employing
      the cellular microindentation tests and fluorescence observation of actin CSK by
      the combination of atomic force microscopy (AFM) and fluorescence microscopy
      (FM). The relationships among cell elasticity, the structural features of actin
      CSK, and engineered cell shape were analyzed and compared with those of control
      cells that had been cultured on nonprocessed surfaces (termed naturally extended
      cells). Results showed that the spindle-shaped cells with sparse or no apical
      stress fibers (ASFs) exhibited similar stiffness to that of the naturally
      extended cells with dense ASFs. The elasticity of spindle-shaped cells was
      affected only slightly by the stress fiber (SF) density, which is in marked
      contrast to the significant correlation shown between cell elasticity and SF
      density in naturally extended cells. This result implies that the elasticity of
      regionally restricted adhesion-surface-induced shape-engineered cells,
      particularly of highly elongated cells, is affected predominantly by cell shape
      rather than by structural features of SFs.

PMID- 17226811
TI  - Fast and efficient screening system for new biomaterials in tissue engineering: a
      model for peripheral nerve regeneration.
AB  - The use of three-dimensional biodegradable matrices is one major issue in tissue
      engineering. Numerous materials, fabrication techniques, and modifications have
      been used and tested in different areas of tissue engineering recently. But
      nevertheless, technology is far from being optimized and optimal constructs with
      bioidentical and mechanical properties have not been described in the literature
      so far. Hence, there is great demand of new suitable biomaterials for tissue
      engineering applications. In this study, a fast and efficient screening system
      for initial testing of biomaterials for cell culture application was developed.
      The set up for the screening system and the decision criteria applied for the
      determination of suitability of new materials are presented. Hep-G2 and PC-12
      cells were seeded onto different matrices and cultured over a period of 2 weeks.
      The viability of the cells was monitored via the MTT assay. Cell spreading was
      investigated by DAPI-staining of cell nuclei. Furthermore, the adhesion of the
      cells on the different matrices was examined by counting the number of attached
      cells. With these general assays a classification of materials is possible with
      regard to their suitability. Optimal cell models must be chosen for the defined
      applications and at least two cell lines are necessary for a differentiating
      interpretation.

PMID- 17226812
TI  - Coding with spike shapes and graded potentials in cortical networks.
AB  - In cortical neurones, analogue dendritic potentials are thought to be encoded
      into patterns of digital spikes. According to this view, neuronal codes and
      computations are based on the temporal patterns of spikes: spike times, bursts or
      spike rates. Recently, we proposed an 'action potential waveform code' for
      cortical pyramidal neurones in which the spike shape carries information. Broader
      somatic action potentials are reliably produced in response to higher conductance
      input, allowing for four times more information transfer than spike times alone.
      This information is preserved during synaptic integration in a single neurone, as
      back-propagating action potentials of diverse shapes differentially shunt
      incoming postsynaptic potentials and so participate in the next round of spike
      generation. An open question has been whether the information in action potential
      waveforms can also survive axonal conduction and directly influence synaptic
      transmission to neighbouring neurones. Several new findings have now brought new
      light to this subject, showing cortical information processing that transcends
      the classical models.

PMID- 17226815
TI  - DNA barcoding in animal species: progress, potential and pitfalls.
AB  - Despite 250 years of work in systematics, the majority of species remains to be
      identified. Rising extinction rates and the need for increased biological
      monitoring lend urgency to this task. DNA sequencing, with key sequences serving
      as a "barcode", has therefore been proposed as a technology that might expedite
      species identification. In particular, the mitochondrial cytochrome c oxidase
      subunit 1 gene has been employed as a possible DNA marker for species and a
      number of studies in a variety of taxa have accordingly been carried out to
      examine its efficacy. In general, these studies demonstrate that DNA barcoding
      resolves most species, although some taxa have proved intractable. In some
      studies, barcoding provided a means of highlighting potential cryptic, synonymous
      or extinct species as well as matching adults with immature specimens. Higher
      taxa, however, have not been resolved as accurately as species. Nonetheless, DNA
      barcoding appears to offer a means of identifying species and may become a
      standard tool.

PMID- 17226814
TI  - Deletion of exon 16 of the dystrophin gene is not associated with disease.
AB  - The DNA of a male harbored a deletion of exon 16 as well as most of introns 15
      and 16 of the dystrophin gene. The person was completely healthy, with universal
      normal muscle strength, and normal muscle histology and creatine kinase levels.
      The deletion was also present in DNA from a muscle biopsy, excluding mosaicism as
      an explanation for the phenotype. We conclude that the protein segment encoded by
      exon 16 of the dystrophin gene is of no importance for the essential function of
      dystrophin. The findings suggest that even large gene re-arrangements of the
      dystrophin gene may not always be disease-causing, and caution a diagnosis of
      dystrophinopathy in sporadic cases of single exon in-frame deletions.

PMID- 17226813
TI  - Aggressiveness and outcome of papillary thyroid carcinoma (PTC) versus
      microcarcinoma (PMC): a mono-institutional experience.
AB  - BACKGROUND: Papillary thyroid carcinoma (PTC) represents 70%-75% of well
      differentiated thyroid cancers. Although most reports have shown that papillary
      thyroid microcarcinomas (PMC) follow an indolent course, a few series have
      demonstrated that a significant number of them are associated with extrathyroidal
      extension and nodal or distant metastases. METHODS: Four hundred eighty-four
      patients with papillary thyroid cancer (102, PMC; 382, PTC) were enrolled in this
      study. The median follow-up was 102 months. RESULTS: No difference between PTC
      and PMC patients was observed for age, gender, multifocality, extrathyroidal
      extension, and lymph nodes metastasis. The prevalence of nodal involvement
      developing during the follow-up period was significantly higher in PMC than PTC
      (58.8% vs. 38.5%, P = 0.002). An unfavorable clinical course occurred in 96
      subjects (21.8%). Logistic analysis showed that the strongest association with
      the worst prognosis was found for age and TNM stage III (P < 0.001). Analysis
      also confirmed that the presence of intranodular vascularity is a predictor of
      unfavorable outcome (P = 0.044). CONCLUSIONS: We suggest always performing a
      total thyroidectomy followed by radiometabolic therapy in papillary carcinomas
      independent of their size. If the choice in PMCs should be more conservative
      (hemithyroidectomy), we purpose to limit this procedure to the cancers without
      Doppler features suggesting intranodular vascular pattern.

PMID- 17226817
TI  - Reply to Butterfield on stem-group "worms": fossil lophotrochozoans in the
      Burgess Shale.

PMID- 17226816
TI  - Goat PRND expression pattern suggests its involvement in early sex
      differentiation.
AB  - Expression of the goat prion protein gene locus was assessed by reverse
      transcriptase-polymerase chain reaction on testes and ovaries at various
      developmental stages. A weak and stochastic expression of the PRNP and PRNT genes
      was observed. For PRNT, it is consistent with the detected deletions of two
      single nucleotides within its open reading frame in ruminant genes. PRND was
      expressed in both tissues at all stages. Whereas its expression is constant in
      the ovaries, it increases in testes between 36 and 46 days postcoitum (dpc) and
      remains high thereafter. In testes, Doppel was found in the nucleus of germinal
      cells and in the cytoplasm of Leydig cells at 44 dpc. It was detected in the
      cytoplasm of Leydig cells and of some Sertoli and germinal cells at 62 dpc. In
      the ovaries, it was observed in the nucleus of germinal cells at 44 dpc and
      mainly in their cytoplasm at 62 dpc. This expression pattern was shown to
      parallel that of C-kit and suggests Doppel involvement in early testis
      differentiation.

PMID- 17226820
TI  - Saphenofemoral junction: the Line of Biglioli.

PMID- 17226819
TI  - Transverse humeral ligament: does it exist?
AB  - The insertion of the tendon of subscapularis is accepted as being on the lesser
      tubercle of the humerus. The transverse humeral ligament (THL) is described as a
      distinct entity in most textbooks, overlying the long tendon of biceps as it
      emerges from the capsule of the shoulder joint. In this study, we dissected 85
      embalmed shoulders to clarify the anatomy of the THL and variation in the
      insertion of the tendon of subscapularis. In all specimens no distinct THL could
      be identified, but in every shoulder a fibrous expansion arose from the posterior
      lamina of the tendon of pectoralis major overlying the long tendon of biceps. In
      86% of shoulders, fibres from the tendon of subscapularis passed over the long
      tendon of biceps within this fibrous expansion and inserted on to the greater
      tubercle of the humerus where one would expect to find the THL. In 33% of
      dissections, fibres from the tendon of subscapularis lay deep to the long tendon
      of biceps, inserting either into the bicipital groove or on to the greater
      tubercle. In only 8% of cases did the tendon of subscapularis insert exclusively
      on to the lesser tubercle. We conclude that the THL does not exist as a separate
      entity. We suggest that in the majority of cases, the structure overlying the
      long tendon of biceps as it emerges from the capsule of the shoulder joint
      consists of tendinous fibres from subscapularis, contained within a fibrous
      expansion derived from the posterior lamina of the tendon of pectoralis major. In
      the minority of shoulders, where the tendon of subscapularis inserts exclusively
      on to the lesser tubercle, we hypothesise that this fibrous expansion acts as a
      retinaculum preventing the long tendon of biceps from "bowstringing."

PMID- 17226821
TI  - Avulsion of ascending lumbar and iliolumbar veins in anterior spinal surgery: an
      anatomical study.
AB  - To expose the disc between the 4th and 5th lumbar vertebrae in anterior spinal
      surgery, left to right retraction of inferior vena cava and aorta is required.
      This manoeuvre can be complicated by venous haemorrhage that, in most cases, is
      due to avulsion of the left ascending lumbar vein (ALV) or the left iliolumbar
      vein (ILV). We dissected 23 embalmed cadavers to assess the factors that
      contribute to the risk of tearing these two veins during retraction. We describe
      a triangular region that should help surgeons in identifying the ALV and ILV.
      This triangle is defined by the lateral border of the common iliac vein, the
      medial border of the psoas major muscle, and the superior end-plate of the L5
      vertebral body. We observed that 3 cm between the termination of the left ALV, or
      a common stem with the ILV, and the termination of the common iliac vein is the
      critical distance, less than which the risk of venous avulsion is highest.
      Although the sample considered is small, our study seems to suggest that male
      patients tend to have a higher risk of venous avulsion than female patients.

PMID- 17226818
TI  - Versican proteolysis mediates myocardial regression during outflow tract
      development.
AB  - An important phase of cardiac outflow tract (OFT) formation is the remodeling of
      the distal region of the common outlet in which the myocardial sleeve is replaced
      by with smooth muscle. Here we demonstrate that expression of the proteoglycan
      versican is reduced before the loss of myocardium from the distal cardiac outlet
      concomitant with an increase in production of the N-terminal cleavage fragment of
      versican. To test whether versican proteolysis plays a role in OFT remodeling, we
      determined the effects of adenoviral-mediated expression of a versican isoform
      devoid of known matrix metalloproteinase cleavage sites (V3) and an N-terminal
      fragment of versican (G1). V3 expression promoted an increase in thickness of the
      proximal OFT myocardial layer independent of proliferation. In contrast, the G1
      domain caused thinning and interruptions of the OFT myocardium. These in vivo
      findings were consistent with findings using cultured primary cardiomyocytes
      showing that the V3 promoted myocardial cell-cell association while the G1 domain
      caused a loss of myocardial cell-cell association. Taken together, we conclude
      that intact versican and G1-containing versican cleavage products have opposing
      effects on myocardial cells and that versican proteolysis may facilitate the loss
      of distal myocardium during OFT remodeling.

PMID- 17226822
TI  - Bony eminence on the middle cranial fossa corresponding to the temporomandibular
      joint.
AB  - We report a nameless bony eminence over the temporomandibular joint (TMJ) and its
      possible clinical significance. Forty-two half heads of 21 UK Caucasian cadavers
      (61-95 years old, mean 84.3 +/- 8.2 years, male:female = 11:10) were used to
      investigate the surface of the middle cranial fossa (MCF) over the TMJ. The
      thickness of the bony roof of the glenoid fossa was also measured. A bony
      eminence over the glenoid fossa was observed in half of the specimens. Some
      showed a complete oval bulge, which completely reflected the contour of the
      glenoid fossa. The others showed a bony bulge, which partially reflected that
      contour. The mean (+/-SD) thickness of the bone in the roof of glenoid fossa was
      1.5 +/- 1.2 mm. The mean bony thickness of specimens showing the eminence was 0.8
      +/- 0.5 mm, whereas it was 2.3 +/- 1.2 mm in specimens without an eminence. These
      differences were statistically significant (P < 0.01). The osteological features
      we describe may be relevant to certain clinical problems. Traumatic dislocation
      of mandibular condyle, for example, might relate to a weakness of the glenoid
      fossa.

PMID- 17226823
TI  - The poor, the Black, and the marginalized as the source of cadavers in United
      States anatomical education.
AB  - When the practice of hands-on anatomical dissection became popular in United
      States medical education in the late 18th and early 19th centuries, demand for
      cadavers exceeded the supply. Slave bodies and thefts by grave robbers met this
      demand. Members of the public were aware that graves were being robbed and
      countered with various protective measures. Since the deterrence of grave robbing
      took time and money, those elements of society who were least economically and
      socially advantaged were the most vulnerable. Enslaved and free African
      Americans, immigrants, and the poor were frequently the target of grave robbing.
      The politically powerful tolerated this behavior except when it affected their
      own burial sites. Slave owners sold the bodies of their deceased chattel to
      medical schools for anatomic dissection. Stories of the "night doctors" buying
      and stealing bodies became part of African American folklore traditions. The
      physical and documentary evidence demonstrates the disproportionate use of the
      bodies of the poor, the Black, and the marginalized in furthering the medical
      education of white elites.

PMID- 17226825
TI  - Extended right trisegmentectomy using in situ hypothermic perfusion with modified
      HTK solution for a large intrahepatic cholangiocarcinoma.
AB  - The technique of right hepatic trisegmentectomy has been standardized for large
      tumors that involve the right lobe and extend into the medial segment of the left
      lobe. However, these tumors are deemed unresectable if they encroach across the
      falciform ligament into the left lateral segment. We report the technique of
      extended right trisegmentectomy in a patient with a large intrahepatic
      cholangiocarcinoma that involved the right lobe of the liver and extended into
      the medial and lateral segments of the left lobe. The resection was performed by
      using total hepatic vascular isolation and in situ hypothermic perfusion with
      modified histidine-tryptophan-ketoglutarate (HTK) solution into the left lateral
      segment. The biliary enteric anastomosis was constructed using a double
      hepaticojejunostomy to Segments II and III bile ducts. The procedure allowed safe
      parenchymal dissection with preservation of the blood supply to Segments II and
      III. Furthermore, in situ hypothermic perfusion protected the remnant liver from
      the deleterious effects of warm ischemia during parenchymal dissection and
      facilitated postoperative recovery. To the best of our knowledge, this is the
      first report of extended right trisegmentectomy for the treatment of intrahepatic
      cholangiocarcinoma in the Western literature.

PMID- 17226826
TI  - Central core disease due to recessive mutations in RYR1 gene: is it more common
      than described?
AB  - Central core disease (CCD) is an autosomal-dominant congenital myopathy, with
      muscle weakness and malignant hyperthermia (MH) susceptibility. We identified two
      of nine Brazilian CCD families carrying two mutations in the RYR1 gene. The
      heterozygous parents were clinically asymptomatic, and patients were mildly
      affected, differing from the few autosomal-recessive cases described previously.
      Recessive inheritance in CCD may therefore be more common than previously
      appreciated, which has important implications for genetic counseling and MH
      prevention in affected families.

PMID- 17226827
TI  - Celiac disease presenting with motor neuropathy: effect of gluten free-diet.
AB  - Celiac disease is a rare cause of neuropathy that most commonly presents with
      symmetric distal sensory disturbances. We describe two patients with celiac
      disease in whom neuropathy presented unusually with progressive weakness of the
      limbs. In both patients a gluten-free diet induced a significant improvement of
      muscle strength and neurophysiological abnormalities, suggesting a direct
      pathogenetic role of sensitivity to gluten. Celiac disease should be considered
      in patients with idiopathic neuropathy even when gastrointestinal symptoms are
      absent.

PMID- 17226828
TI  - The performance of the new 6-31G(##) basis set: molecular structures and
      vibrational frequencies of transition metal carbonyls.
AB  - The performance of the newly proposed 6-31G(##) basis set for calculating the
      equilibrium structure and vibrational frequencies of transition metal carbonyl
      complexes has been studied at the HF and DFT levels of theory. The 6-31G(##)
      basis set has been constructed by augmentation of the 6-31G basis set by diffuse
      and polarization functions, which are generated from the corresponding 6-31G
      basis AOs response functions obtained in the frame of propagator approach. The
      predicted values of bond distances and vibrational frequencies for the title
      compounds are in good agreement with the experimental data. The relative energies
      and HOMO-LUMO gaps were also estimated for the series of MCO complexes.

PMID- 17226830
TI  - Theoretical study and rate constant calculation for reaction of CF(3)CH(2)OH with
      OH.
AB  - The reaction mechanism of CF(3)CH(2)OH with OH is investigated theoretically and
      the rate constants are calculated by direct dynamics method. The potential energy
      surface (PES) information, which is necessary for dynamics calculation, is
      obtained at the B3LYP/6-311G (d, p) level. The single-point energy calculations
      are performed at the MC-QCISD level using the B3LYP geometries. Complexes, with
      the energies being less than corresponding reactants and products, are found at
      the entrance and exit channels for methylene-H-abstraction channel, while for the
      hydroxyl-H-abstraction channel only entrance complex is located. By means of
      isodesmic reactions, the enthalpies of the formation for the species
      CF(3)CH(2)OH, CF(3)CHOH, and CF(3)CH(2)O are estimated at the MC-QCISD//B3LYP/6
      311G (d, p) level of theory. The rate constants for two kinds of H-abstraction
      channels are evaluated by canonical variational transition state theory with the
      small-curvature tunneling correction (CVT/SCT) over a wide range of temperature
      200-2000 K. The calculated results are in good agreement with the experimental
      values in the temperature region 250-430 K. The present results indicate that the
      two channels are competitive. Below 289 K, hydroxyl-H-abstraction channel has
      more contribution to the total rate constants than methylene-H-abstraction
      channel, while above 289 K, methylene-H-abstraction channel becomes more
      important and then becomes the major reaction channel.

PMID- 17226829
TI  - The way of stabilizing non-IPR fullerenes and structural elucidation of
      C(54)Cl(8).
AB  - Recently, a new non-IPR chlorofullerene C(54)Cl(8) was isolated experimentally
      (Science 2004, 304, 699). To explore the ways to stabilize non-IPR fullerenes,
      the authors studied all of the possible isomers of C(54) fullerene and some of
      the C(54)Cl(8) isomers at PM3, B3LYP/3-21G, and B3LYP/6-31G* levels. Combined
      with analysis of pentagon distributions, bond resonance energies, and steric
      strains, C(54):540 with the least number of 5/5 bonds was determined to be the
      thermodynamically best isomer for the C(54)Cl(8). Based on C(54):540, the most
      probable structure of the experimental C(54)Cl(8) was elucidated. The results
      suggested one of the necessary conditions of stabilizing non-IPR fullerenes:
      chemical derivatizations of either endohedral complexation or exohedral addition
      need to sufficiently stabilize all of the kinetically unstable 5/5 bonds of the
      cages.

PMID- 17226831
TI  - Theoretical density functional theory studies on interactions of small
      biologically active molecules with isolated heme group.
AB  - We present ab-initio density functional theory studies on the interactions of
      small biologically active molecules, namely NO, CO, O(2), H(2)O, and NO(2) (-)
      with the full-size heme group. Our results show that the small molecule-iron bond
      is the strongest in carbonyl and the weakest in nitrite system. Trans influence
      induced by NO binding to the five-coordinate heme complex is shown. Nitric oxide
      in the resulting complex might be described as NO(-). The differences among the
      small ligands of XO type (CO, NO, O(2)), and their distant chemical behavior from
      H(2)O and NO(2) (-) ligands in binding to the Fe(II) ion, are shown. Moreover,
      the role of the heme ring as a reservoir of electrons in the studied complexes is
      invoked. The analysis of the parameters defining the iron-histidine bond
      indicates that this bond is longer and weaker in nitrosyl and carbonyl complexes
      than in the other systems. Our findings support the proposed mechanism of soluble
      guanylate cyclase (sGC) activation and suggest that the first step of sGC
      activation by CO may be the same as during the activation by NO. Obtained results
      are then compared with the data concerning smaller model of the heme, the
      porphyrin complexes, available in the literature.

PMID- 17226832
TI  - Point scattering: a new geometric invariant with applications from (nano)clusters
      to biomolecules.
AB  - A new geometric invariant is defined from "first principles" for a point
      ensemble, which can represent clusters, molecules, crystals, and biomolecules.
      The scattering of a point ensemble is defined in terms of the Euclidean distance
      matrix and a vector measuring the weighted departure of the points from the
      cluster centre. Using the Rayleigh-Ritz theorem this function is maximized
      obtaining the point scattering of the ensemble. The point scattering shows
      several properties which are useful for studying clusters, molecules, crystals,
      and biomolecules. We examined different natural clusters of hard spheres such as
      colloidal particles and fullerenes, as well as protein-peptide complexes and the
      effect of temperature on protein structure. In all cases point scattering
      differentiates point ensembles with different structures, which are not
      distinguished by other geometric invariants, such as the second moment of mass
      distribution, surface areas, and volumes. Point scattering also shows better
      correlation with thermodynamic parameters of binding and describes the interior
      cavities of hollowed ensembles better than the other geometric measures.

PMID- 17226833
TI  - Calculations of frequency-dependent molecular magnetizabilities with quasi
      relativistic time-dependent generalized unrestricted Hartree-Fock method.
AB  - The time-dependent generalized unrestricted Hartree-Fock (TDGUHF) method combined
      with a two-component quasi-relativistic Hamiltonian generated from the Douglas
      Kroll-Hess (DKH) transformation was developed to calculate frequency-dependent
      molecular magnetizabilities, which are the linear response quantity of a molecule
      to an external magnetic field. By calculating the magnetizabilities of H(2)X (X =
      O, S, Se, and Te), the noble gases (He, Ne, Ar, Kr, and Xe) and small open shell
      molecules (CH(2), CH(3), and O(2)), we found that scalar relativistic terms
      affect mainly the diamagnetic magnetizability and spin-orbit (SO) interaction
      affects the paramagnetic magnetizability.

PMID- 17226834
TI  - Thermodynamic calculations for molecules with asymmetric internal rotors-
      application to 1,3-butadiene.
AB  - We present quantum mechanical partition functions, free energies, entropies, and
      heat capacities of 1,3-butadiene derived from ab initio calculations. Our
      technique makes use of a reaction path-like Hamiltonian to couple all 23
      vibrational modes to the large-amplitude torsion, which involves heavy asymmetric
      functional groups. Ab initio calculations were performed at the B3LYP, MP2, and
      CCSD(T) levels of theory and compared with experimental values as a reference
      case. By using the ab initio potentials and projected frequencies, simple
      perturbative expressions are presented for computing the couplings of all the
      vibrational modes to the large-amplitude torsion. The expressions are
      particularly suited for programming in the new STAR-P software platform which
      automatically parallelizes our codes with distributed memory via a familiar
      MATLAB interface. Using the efficient parallelization scheme of STAR-P, we obtain
      thermodynamic properties of 1,3-butadiene for temperatures ranging from 50 to 500
      K. The free energies, entropies, and heat capacities obtained from our
      perturbative formulas are compared with conventional approximations and
      experimental values found in thermodynamic tables.

PMID- 17226835
TI  - Optimized Monte Carlo sampling in forward-backward semiclassical dynamics.
AB  - Forward-backward semiclassical dynamics (FBSD) provides a rigorous and powerful
      methodology for calculating time correlation functions in condensed phase systems
      characterized by substantial quantum mechanical effects associated with zero
      point motion, quantum dispersion, or identical particle exchange symmetries. The
      efficiency of these simulations arises from the use of classical trajectories to
      capture all dynamical information. However, full quantization of the density
      operator makes these calculations rather expensive compared to fully classical
      molecular dynamics simulations. This article discusses the convergence properties
      of various correlation functions and introduces an optimal Monte Carlo sampling
      scheme that leads to a significant reduction of statistical error. A simple and
      efficient procedure for normalizing the FBSD results is also discussed.
      Illustrative examples on model systems are presented.

PMID- 17226836
TI  - Generation of basis sets with high degree of fulfillment of the Hellmann-Feynman
      theorem.
AB  - A direct relationship is established between the degree of fulfillment of the
      Hellman-Feynman (electrostatic) theorem, measured as the difference between
      energy derivatives and electrostatic forces, and the stability of the basis set,
      measured from the indices that characterize the distance of the space generated
      by the basis functions to the space of their derivatives with respect to the
      nuclear coordinates. On the basis of this relationship, a criterion for obtaining
      basis sets of moderate size with a high degree of fulfillment of the theorem is
      proposed. As an illustrative application, previously reported Slater basis sets
      are extended by using this criterion. The resulting augmented basis sets are
      tested on several molecules finding that the differences between energy gradient
      and electrostatic forces are reduced by at least one order of magnitude.

PMID- 17226837
TI  - Site specificity of alpha-H abstraction reaction among secondary structure motif-
      an ab initio study.
AB  - The initial step of protein oxidation is studied through alpha-H abstraction by
      an OH radical with various secondary structure motifs of proteins. It is found
      that there exist preferential alpha-Hs in this kind of abstractions. The typical
      abstraction mechanism involves three steps: forming a pre-reactive complex before
      abstraction, the abstraction reaction, and the H(2)O detachment from a post
      reactive complex to form the product, C(alpha)-center radical. Using the
      stability of the pre-reactive complex and the reaction barrier, we provide some
      explanation for this site preference. The feasibility of alpha-H abstraction by
      OH radical depends not only on the types of secondary structure, but also on the
      reaction condition, such as in aqueous or in gas phase. Moreover, the reactivity
      of the abstraction also depends on the location of alpha-H in the secondary
      structure motifs. The preferential alpha-Hs to be abstracted in beta-sheet are
      those immediate to the amide or carbonyl group, and without involving hydrogen
      bonding, whereas in reverse turns, the preferential alpha-Hs are near the C
      terminal of type I and near the N-terminal of type II. In general, the alpha-Hs
      in alpha-helix are more difficult to be abstracted than those in beta-sheet and
      polypeptide in linear form. It is consistent with the trend of their bond
      dissociation energies. Our theoretical rate constant of N-acetyldiglycin
      methylamide (Ac(Gly)(2)NHCH(3)) in aqueous solution (6.75 x 10(8) M(-1) s(-1)) is
      close to the experimental observation of N-acetyldiglycinamide (Ac(Gly)(2)NH(2))
      (8.6 x 10(8) M(-1) s(-1)).

PMID- 17226838
TI  - Finite group theory for large systems. 3. Symmetry-generation of reduced matrix
      elements for icosahedral C(20) and C(60) molecules.
AB  - This paper uses symmetry-generation to simplify the determination of Hamiltonian
      reduced matrix elements. It is part of a series on using computers to apply
      finite group theory to quantum mechanical calculations on large systems. Symmetry
      generation is an expression of the whole molecule as a sum of symmetry
      transformations on a smaller reference structure. Then on a suitably-conditioned
      symmetry-adapted basis, the reduced matrix elements of the Hamiltonian are
      averages of certain elements of the simpler reference structure matrix. The
      smaller the reference structure, the greater is the computational savings. Single
      atom reference structures are used here for the Huckel treatment of icosahedral
      C(20) and C(60) fullerenes. The analytical power of this approach is illustrated
      by determining the two bond lengths of C(60) from spectral data.

PMID- 17226839
TI  - Theoretical study of the electronic spectra of oxidized and reduced states of
      lumiflavin and its derivative.
AB  - Time-dependent density functional theory has been applied to investigate the
      electronic absorption spectrum of oxidized and reduced lumiflavin and its
      derivative, 8-NH(2)-lumiflavin. The calculations allow the authors to explain the
      origin of the difference in spectral features between oxidized and reduced states
      of lumiflavin. For the reduced lumiflavin, a reasonable assignment of the
      experimental spectrum has been made for the first time. Furthermore, the results
      obtained reveal that the NH(2) group plays a critical role in shaping the
      spectral features of 8-NH(2)-lumiflavin, and offer a reasonable explanation for
      the spectral changes upon substituting the NH(2) group for the CH(3) group of
      lumiflavin.

PMID- 17226840
TI  - Long range behavior of high-rank topological multipole moments.
AB  - The construction of a high-rank multipolar force field (for peptides) is a
      complex task, leading to several intermediate questions in need of a clear
      answer. Here we focus on the convergence of the (electrostatic) multipolar
      expansion at medium and long range. Using molecular electron densities, quantum
      chemical topology (QCT) defines the atoms as finite volumes, each endowed with
      multipole moments. The terms in the multipole expansion are grouped according to
      powers of the internuclear distance, R(-L). Given two atom types at a given
      distance, we determine which rank (L) is necessary for the electrostatic energy
      to converge to the exact interaction energy within a certain error. With this
      information, the rank of the expansion for each interaction can be adapted to the
      required accuracy and the available computing power.

PMID- 17226841
TI  - When to start supplementary iron to prevent iron deficiency in early childhood in
      sub-Saharan Africa setting.
AB  - BACKGROUND: To study the efficacy of oral ferrous fumarate, an inexpensive,
      readily available preparation on iron deficiency in infants in Africa. PROCEDURE:
      Four months old (group 1, n = 252) and 6-18 months old (group 2, n = 360) healthy
      infants attending four primary health care centers (PHC) for vaccination/well
      child visits in Benin were studied. Ninety-six pregnant women (PW) over 36 weeks
      gestational age attending the same PHC during the study period were also studied.
      Infants were offered 2 months supplementation with oral powdered generic ferrous
      fumarate (GFF), that is, 5 mg/kg/day of elemental iron, given twice and were
      reevaluated 2 months later for hematological indices. The prevalence of anemia
      and iron deficiency among pregnant women was assessed using hematological indices
      and transferrin saturation. RESULTS: The prevalence of anemia was 42.0%, 61.9%,
      and 37.5% in groups 1, 2, and PW, respectively. All anemic PW were iron
      deficient. Hemoglobin level shifted towards high values after supplementation. In
      addition, 24 infants from group 1 whose mothers interrupted the treatment, showed
      a significant decrease in hemoglobin level values, and similar improvement after
      two additional months of supplementation. CONCLUSION: Programs to prevent iron
      deficiency in Africa should utilize inexpensive preparations, start during
      pregnancy, continue in infants at 3 months of age and address problems of
      noncompliance.

PMID- 17226842
TI  - Interstitial brachytherapy for childhood soft tissue sarcoma.
AB  - BACKGROUND: To evaluate the efficacy of interstitial brachytherapy (BRT) in
      children undergoing combined modality treatment for soft tissue sarcomas (STS).
      PROCEDURE: From September 1984 to December 2003, 50 children (median age 13
      years, range 1 to 18) with STS who received BRT as part of loco-regional
      treatment were included. There were 30 males and 20 females, the majority (68%)
      had primary lesions, synovial sarcoma (32%) was the most common histological
      type, and 26% had high-grade lesions. Treatment included wide local excision and
      BRT with or without external beam radiotherapy (EBRT). Thirty children (60%)
      received BRT alone. RESULTS: After a median follow-up of 51 months, the local
      control (LC), disease-free survival, and overall survival were 82%, 68%, and 71%,
      respectively. LC was superior in patients with tumor size </=5 cm versus >5 cm
      (96% vs. 67%, P = 0.04), symptom duration <2 months versus >2 months (100% vs.
      73%, P = 0.05), and Grade I versus Grade II versus Grade III tumors (100% vs. 93%
      vs. 57%, P = 0.03). Children receiving a combination of BRT and EBRT had
      comparable LC to those receiving BRT alone (78% vs. 84%, P = 0.89). There was no
      significant difference in LC for patients receiving LDR versus HDR BRT (77% vs.
      92%, P = 0.32, for BRT alone; and 67% vs. 100%, P = 0.17, for BRT + EBRT).
      CONCLUSION: Interstitial BRT with or without EBRT appears to result in
      satisfactory outcome in children with STS. Radical BRT alone, when used
      judiciously in select groups of children, results in excellent local control and
      functional outcome with reduced treatment-related morbidity.

PMID- 17226843
TI  - Treatment of neuroblastoma-related opsoclonus-myoclonus-ataxia syndrome with high
      dose dexamethasone pulses.
AB  - Opsoclonus-myoclonus-ataxia-syndrome (OMS) represents a rare neuroblastoma
      associated paraneoplastic syndrome that commonly results in neurologic deficits
      despite tumor resection and immunosuppressive therapy. We describe the response
      of five such children to high-dose dexamethasone pulses including two patients in
      whom previous glucocorticoids, rituximab, and cytostatic drugs were not
      successful. All patients had MYCN non-amplified tumors that were detected 1 to 7
      months after the onset of the OMS or ataxia. This treatment resulted in a good
      partial response in three and in complete remission in two patients. Our results
      show that dexamethasone pulses are likely to be useful for both, first-line- and
      salvage-therapy for OMS-patients.

PMID- 17226844
TI  - Cause of mortality in 5-year survivors of childhood cancer.
AB  - Survivors of childhood and adolescent cancer are at risk for long-term effects of
      disease and treatment. The Childhood Cancer Survivor Study assessed overall and
      cause-specific mortality in a retrospective cohort of 20,690 5-year survivors.
      Eligible subjects were individuals diagnosed with cancer (from 1970 to 1986)
      before the age of 21 who had survived 5 years from diagnosis. Underlying cause of
      death was obtained from death certificates and other sources, then and coded and
      categorized as recurrent disease, sequel of cancer treatment, or non-cancer
      related. Age and sex standardized mortality ratios (SMRs) were calculated using
      United States population mortality data. The cohort demonstrated an 8.2-fold
      excess in overall mortality (95% confidence interval, 7.9 to 8.5). Recurrence of
      the original cancer was the leading cause of death among 5-year survivors,
      accounting for 57% of deaths. Statistically significant excess mortality rates
      were seen due to subsequent malignancies (SMR = 15.0), along with cardiac (SMR =
      6.9), and pulmonary (SMR = 8.7). There was no increase seen for automotive
      accidents (SMR = 1.0), other accidents (SMR = 1.3), or suicide (SMR = 1.0). While
      recurrent disease remains a major contributor to late mortality in 5-year
      survivors of childhood cancer, significant excesses in mortality risk associated
      with treatment-related complications exist up to 25 years after the initial
      cancer diagnosis.

PMID- 17226846
TI  - Long-term complications of treatment of children and adolescents with cancer:
      gene polymorphisms and causes of excess mortality.

PMID- 17226845
TI  - The future of pediatric cancer and complex diseases: aren't they all?
AB  - Over the past decade, the investigation of human genetics and disease has pursued
      both common and uncommon germ-line variation and shown that both can be
      associated with altered risk for cancer and its outcomes. This line of
      investigation has not only begun to generate markers for disease but also
      insights into the biological pathways that are altered in cancer. Already, there
      is emerging evidence that germ-line genetic variation can alter susceptibility to
      different types of cancers, including pediatric cancers. It is evident that
      common genetic variation has emerged as a key component of a comprehensive
      understanding of pediatric cancer and its outcome. Future studies should unravel
      the complex interaction between genes and the environment.

PMID- 17226847
TI  - Osteosarcoma metastatic to the kidney and iatrogenic hemorrhage.
AB  - A 16-year old female presented painful masses in the lumbar region 5 years after
      the initial diagnosis of a localized osteosarcoma of the tibia. Abdominal X-ray
      revealed calcified masses. A bone scan confirmed an increased uptake in the renal
      areas. An ultrasound-guided fine needle biopsy confirmed the diagnosis of
      metastases. The procedure was complicated by subcapsular hemorrhage and gross
      hematuria. Renal metastases from osteosarcoma are usually asymptomatic and
      invisible on abdominal X-rays. The diagnosis is generally established by
      radionuclide bone scan or abdominal CT-scan. Our observation suggests that
      histological documentation of these unusual clinical presentations should be
      carefully weighed against the risk of the procedure.

PMID- 17226848
TI  - A stress echocardiography study of cardiac function during progressive exercise
      in pediatric oncology patients treated with anthracyclines.
AB  - BACKGROUND: Anthracycline-treated patients (AP) are at risk for cardiac
      dysfunction years after treatment. Cardiac function has not been evaluated during
      exercise in AP. The purpose of this study was to assess exercise tolerance, left
      ventricular (LV) function, and hemodynamics during progressive exercise.
      PROCEDURE: We studied 47 AP (cumulative dose: 36-504 mg/m(2)) who were in
      complete remission and 12 healthy controls (CON). AP were further grouped by
      cumulative dose (LOW <or= 260 mg/m(2); HIGH >or= 260 mg/m(2)) and resting
      echocardiographic function. All subjects performed 3-min incremental stages on a
      semi-recumbent cycle ergometer until volitional fatigue. Using echocardiography
      and Doppler, LV dimensions, posterior wall thickness (LVPWs), peak aortic
      velocity (PAoV), shortening fraction (SF), rate-corrected mean velocity of fiber
      shortening (MVCFc), wall stress at peak systole (sigmaPS), stroke volume index
      (SVI), and cardiac index (CI) were determined. Measurements were performed at
      rest, during each stage of exercise, and in recovery. RESULTS: AP did less work
      than CON (P < 0.050). CON and LOW had similar resting function, while HIGH had a
      lower SF and MVCFc (P < 0.050) and a higher sigmaPS (P < 0.001). Resting SVI and
      CI were also lower in HIGH. At peak exercise, MVCFc and sigmaPS remained
      different in HIGH, and both AP groups had a lower SF, SVI, and CI (P < 0.001). AP
      had an abnormal SVI response to exercise. AP showed a smaller initial increase in
      SVI that was not maintained throughout exercise. CONCLUSIONS: AP have reduced
      exercise tolerance. There also appears to be a dose-related effect on myocardial
      contractility and SVI. These findings may help to guide treatment.

PMID- 17226849
TI  - Incidence of childhood cancer in Switzerland: the Swiss Childhood Cancer
      Registry.
AB  - BACKGROUND: This report describes the incidence of childhood cancer in
      Switzerland, based on the data from the Swiss Childhood Cancer Registry (SCCR), a
      national hospital-based cancer registry with very high coverage, founded in 1976
      by the Swiss Paediatric Oncology Group (SPOG). PROCEDURE: Malignancies were coded
      according to the International Classification of Childhood Cancer (ICCC-3).
      Incidence rates per 100,000 person-years were calculated for all malignancies and
      groups of malignancies in Swiss residents less than 15 years of age for the
      decade 1995-2004. RESULTS: The SCCR annually registered on average 174 new cases
      of cancer in Swiss residents aged <15 years, with a median age at diagnosis of
      5.6 years. The crude incidence of childhood cancer in children aged <15 years was
      13.5, higher for boys (15.0 per 100,000) than for girls (12.1 per 100,000), and
      was nearly twice as high in the first 5 years of life (19.3 per 100,000) than in
      the age group 5 to 14 years (10.8 per 100,000). CONCLUSION: Incidence of
      childhood cancers in the SCCR was similar to neighbouring countries and to data
      published by regional cancer registries in Switzerland for the same period,
      suggesting good completeness of registration. This makes the SCCR a valuable
      resource for national and international research on childhood cancer.

PMID- 17226850
TI  - Treatment of recurrent clear cell sarcoma of the kidney with brain metastasis.
AB  - BACKGROUND: Clear cell sarcoma of the kidney (CCSK) is known for its propensity
      to metastasize to bone, but it also spreads to other sites including the brain.
      This study was undertaken to describe the treatment and outcomes of patients with
      recurrent CCSK involving the brain. METHODS: A retrospective records review was
      conducted on eight patients with CCSK who developed brain metastases after
      complete responses to initial therapy. RESULTS: The recurrences occurred at a
      median of 24.5 months after initial diagnosis (range, 12-53 months). At the time
      of recurrence, patients were treated with multimodal therapy including biopsy or
      resection, radiation therapy, and chemotherapy. All patients received a variable
      number of courses of ifosfamide, carboplatin, and etoposide (ICE), with or
      without other agents. Four patients received high-dose chemotherapy with
      autologous stem cell rescue. One patient died from complications of bacteremia 8
      weeks after starting chemotherapy. The other seven patients achieved a complete
      response after either surgery or ICE chemotherapy. Of these, six patients were
      alive without disease with a median follow-up of 30 months from the time of
      recurrence (range, 24 to 71 months). All six survivors received radiation therapy
      and four had gross total resections. Three survivors received high-dose
      chemotherapy with stem cell rescue. CONCLUSION: Patients with recurrent CCSK
      involving the brain can have durable survival after recurrence. ICE chemotherapy,
      together with radiation therapy and surgery, provides a reasonable salvage
      regimen for recurrent CCSK. It is unclear whether high-dose chemotherapy confers
      a benefit compared to conventional-dose chemotherapy.

PMID- 17226851
TI  - A pilot intervention to enhance psychosexual development in adolescents and young
      adults with cancer.
AB  - BACKGROUND: Evidence suggests that cancer diagnosed during adolescence and young
      adulthood may present considerable challenges to what would otherwise be a
      relatively smooth developmental trajectory, particularly in areas related to
      reproductive health. We created and pilot tested a two-session, individually
      delivered, counseling intervention to enhance psychosexual development in this
      unique population. PROCEDURES: A total of 21 patients, aged 15 to 25 years and
      treated for cancer within the past 5 years, completed the counseling
      intervention. Patients were adaptively randomized to begin the intervention
      immediately, or to be placed on a 3-month waitlist, after which time, they were
      reassessed and began the intervention. The content of the intervention included
      education, dialog, and support regarding cancer and such issues as sexual
      development and function, body image, fertility, prevention of sexually
      transmitted disease and unwanted pregnancy, and romantic relationships (e.g.,
      dating, sexual communication). A 1-month follow-up booster call followed the
      intervention. Questionnaires were completed at baseline, post-waitlist (for half
      the sample), post-treatment, and at 3-month follow-up. RESULTS: Participation in
      the intervention increased cancer-specific knowledge regarding sexual issues;
      improved body image; lessened anxiety about sexual and romantic relationships;
      and decreased overall level of psychological distress. Gains were maintained
      through the 3-month follow-up. CONCLUSIONS: Addressing issues of reproductive
      health in the adolescent/young adult with cancer can and should be offered as a
      part of comprehensive pediatric cancer care.

PMID- 17226852
TI  - Oral anticoagulation with warfarin is significantly influenced by steroids and
      CYP2C9 polymorphisms in children with cancer.
AB  - Clinical management of warfarin therapy is complex, and dosing algorithms do not
      include genetic factors or interactions with other drugs for warfarin dose
      determinations. We evaluated the interaction of warfarin and CYP2C9 polymorphisms
      and concomitant corticosteroids in 29 children with cancer. Children with
      heterozygous polymorphisms of CYP2C9 achieved target INR sooner and more
      frequently had INR above the target level, compared to children without
      mutations. Children on concomitant steroids had significantly lower warfarin
      requirements. Thus, awareness of CYP2C9 genotype and steroid-induced
      responsiveness to warfarin may be important when administrating oral
      anticoagulation in children.

PMID- 17226853
TI  - Evidence about HUI and hemophilia in response to Young et al. "How well does the
      Canadian hemophilia outcomes-kids' life assessment tool (CHO-KLAT) measure the
      quality of life of boys with hemophilia?".

PMID- 17226854
TI  - Midbrain sonography in patients with essential tremor.
AB  - Several studies have reported an increased risk to develop Parkinson's disease
      (PD) in essential tremor (ET) populations. Hyperechogenicity of the substantia
      nigra (SN) is a common transcranial sonography (TCS) finding in PD and has been
      suggested as a PD risk-marker in nonparkinsonian subjects. This study compared SN
      areas of 44 ET patients with 100 controls and 100 PD patients. Sixteen percent of
      ET patients had SN hyperechogenicity as compared with 3% of controls and 75% of
      PD patients. These findings might correspond to an increased risk of ET patients
      to develop PD. Long-term follow-up will show if those with hyperechogenic SN
      develop PD, while these without will not.

PMID- 17226855
TI  - Exercise improves efficacy of levodopa in patients with Parkinson's disease.
AB  - The objective was to investigate the impact of exercise on absorption and
      efficacy of levodopa (LD) in patients with Parkinson's disease (PD). A soluble,
      immediate release LD formulation was given followed by exercise near the aerobic
      limit on one day to PD patients, who underwent the same procedure only at rest on
      the second day. LD plasma behavior did not significantly differ between both
      conditions, but the motor response was significantly better 120 and 150 min after
      LD intake on the day with exercise than on the day with rest. Moderate exercise
      increases clinical efficacy of LD.

PMID- 17226856
TI  - Characteristics of sensory trick-like manoeuvres in jaw-opening dystonia.
AB  - We evaluated the effect of different manipulations on the performance of a
      standardized counting task in 7 patients with idiopathic jaw-opening dystonia.
      Patients used a small stick as sensory stimulus. Following conditions were
      examined: stick placed between teeth and cheek (CHEEK), biting on stick (TEETH),
      voluntary jaw occlusion without stick (OCCLUSION). Articulation was rated by
      patients and experimenters and surface electromyographic activity (EMG) was
      recorded. Patient-rating (CHEEK - 36.6%, TEETH - 48.1%) and EMG (-18.1%; -17.3%)
      were significantly improved for conditions using the stick, whereas experimenter
      rating showed a trend for TEETH (-16.2%). Although jaw occlusion during speaking
      deteriorates articulation in healthy subjects, there was no further deterioration
      in patients and EMG was even significantly reduced (-18.6%). Comparable results
      were obtained in 1 patient using a special dental device. We conclude that
      sensory tricks significantly improve subjective and objective parameters. Besides
      tactile stimulation, altered proprioceptive feedback and antagonist activation
      may modulate hyperactive dystonic networks.

PMID- 17226857
TI  - Impaired motor imagery in patients with essential tremor: a case control study.
AB  - Motor imagery (MI), which refers to the process of mental representation of
      movements, has not been studied in patients with essential tremor (ET). We
      investigated the presence of impaired MI in ET patients compared with healthy
      controls. A group of drug-naive and nondemented ET patients and age-matched
      controls were studied using transcranial magnetic stimulation, while they were
      specifically instructed to try and imagine themselves performing two motor tasks.
      The various clinical and electrophysiological variables were evaluated and
      compared. Repeated measures ANOVA demonstrated a significant difference between
      ET patients and controls with respect to mean motor-evoked potential (MEP)
      amplitudes (F(1,38) = 31.92, P < 0.005) during MI. The process of MI effectively
      facilitated MEP amplitude in controls but not in ET patients, regardless of side
      of stimulation or motor tasks. We provide evidence to demonstrate impairment of
      MI in a group of ET patients compared with healthy controls. The basis for this
      novel finding is unclear, and further studies are warranted to determine whether
      it is related to cerebellar or motor cortical dysfunction.

PMID- 17226858
TI  - Postural responses to continuous unilateral neck muscle vibration in standing
      patients with cervical dystonia.
AB  - Several observations support the notion that integration of neck proprioceptive
      input is impaired in cervical dystonia (CD). An example is the inconsistent or
      opposite to normal effect of lateral neck muscle vibration on body rotation
      during stepping. We hypothesized that lateral neck vibration produces abnormal
      responses also in a static task. Normal subjects and patients with CD stood
      quietly with eyes closed, without or with vibration applied to the
      sternocleidomastoid muscle, and center of foot pressure and body sway were
      recorded by a dynamometric platform. Patients had a larger than normal sway under
      control condition. They showed little or no postural responses to vibration. When
      body tilt occurred, it was rarely in the frontal plane as in normal subjects, but
      in the sagittal plane. No relationship existed between vibration-induced tilt
      during stance and body rotation during stepping. Therefore, in CD, proprioceptive
      neck input is less used for the construction of the postural vertical during
      quiet stance than it is used for the definition of the subjective straight ahead
      during a dynamic task.

PMID- 17226859
TI  - Endothelial cells in peripheral blood of healthy subjects and patients with
      metastatic carcinomas.
AB  - BACKGROUND: A lack of standardized assays and consensus of cell definition has
      lead to a wide variation in the reported range of circulating endothelial cells
      (CECs). METHODS: An automated rare cell analysis system was used to enumerate
      nucleated, CD146+/CD105+/CD45- CECs in 4 mL of blood. RESULTS: Recoveries of
      spiked HUVECs were linear over a range of 0-1,241 cells (R2>or=0.99) with
      recoveries of >or=70% at each spike level. Correlation coefficient values for
      interoperator variability and duplicate sample variation were (R2=0.99 and 0.90),
      respectively. Correlation of CEC counts between tubes 1-2 and 2-3 drawn from the
      same subject in sequence differed (R2=0.48 and 0.63, respectively). The normal
      CEC reference range established in 249 healthy donors was 1-20 CECs/mL blood. CEC
      counts were significantly higher in the 206 metastatic carcinoma patients
      (P<0.0001). CONCLUSION: CECs can be accurately and reproducibly enumerated in
      blood and are elevated in metastatic carcinomas compared with healthy donors.
      Phlebotomy procedures can affect endothelial cell counts.

PMID- 17226860
TI  - A high-throughput 3-parameter flow cytometry-based cell death assay.
AB  - Apoptosis plays a role in many disease states, and the evaluation of novel
      therapeutics that alters the apoptotic cascade is an area of intense
      investigation. However, many generally available methods to evaluate cell death
      are either time consuming, imprecise, or both. We report a system that permits
      simultaneous evaluation of three apoptotic markers (cell membrane integrity,
      mitochondrial membrane potential, and cell cycle progression) with minimal
      technical manipulation. This system is particularly well-suited for toxicologic
      evaluation of novel compounds and profiling of new apoptosis-inducing agents.

PMID- 17226861
TI  - Drug resistance in B-cell chronic lymphocytic leukemia: predictable by in vitro
      evaluation with a multiparameter flow cytometric cytotoxicity assay.
AB  - BACKGROUND: Patients with B-cell chronic lymphocytic leukemia (B-CLL) often
      demonstrate variable responses to similar treatments. It would be highly
      desirable to develop a personalized therapeutic strategy for selection of
      appropriate drugs or regimens based on the drug sensitivity profiles of leukemic
      cells from individuals. METHODS: We applied a multiparameter flow cytometric drug
      cytotoxicity assay to evaluate drug effects specifically on B-CLL cells from 43
      individuals after leukemic cells were incubated in vitro with fludarabine,
      chlorambucil, cladribine, or prednisolone. RESULTS: We demonstrated that
      different B-CLL cell populations from 43 individuals showed a marked variability
      in drug sensitivity. In vitro resistance to fludarabine was greatest in B-CLL
      cells with deletions of p53, a cytogenetic abnormality that is almost invariably
      associated with a poor therapeutic response clinically. CONCLUSIONS: In vitro
      drug sensitivity profiles analyzed by a multiparameter flow cytometric
      cytotoxicity assay may serve as a tool to facilitate individualized selection of
      appropriate drugs for treatment in B-CLL. Prospective trials will be needed to
      validate the clinical utility of this flow cytometric cytotoxicity assay.

PMID- 17226862
TI  - Influence of 4- and 6-color flow cytometers and acquisition/analysis softwares on
      the determination of lymphocyte subsets in HIV infection.
AB  - BACKGROUND AND OBJECTIVES: Lymphocyte immunophenotyping provides valuable
      information for the diagnosis and monitoring of patients with cellular
      immunodeficiencies, such as HIV/AIDS. In this study, we have assessed the
      influence of 4-color and 6-color flow cytometers, and respective analytical
      softwares on the enumeration of lymphocytes in HIV infected individuals. METHODS:
      The expression of various cell surface markers on lymphocytes was measured from
      the EDTA blood of 66 HIV infected patients on the FACSCalibur (4-color) and
      FACSCanto (6-color) flow cytometers. Percentage of lymphocytes expressing a
      particular cell surface marker was analyzed on FACSCalibur using the Cell Quest
      Pro software (v 5.2), while the analysis on FACSCanto was done using FACSCanto (v
      1.0.3) and FACSDiva (v 4.1) softwares respectively. RESULTS: The data shows
      significantly higher mean CD3 T-cell counts on FACSCalibur, Cell Quest Pro (1,864
      +/- 1,044 cells/microl) as compared to FACSCanto (1,840 +/- 1,040 cells/microl)
      (P < 0.05). The CD4 T-cell counts were also higher on FACSCalibur, Cell Quest Pro
      (885 +/- 770 cells/microl), and FACSDiva (892 +/- 773 cells/microl) versus
      FACSCanto (867 +/- 767 cells/microl) (P < 0.05). FACSCalibur, Cell Quest Pro, and
      FACSDiva showed similar values except for CD8 T-lymphocytes where FACSDiva had
      significantly lower values (P < 0.05). The B-cell counts were unaffected when
      either of the instruments or softwares were used, while the natural killer (NK)
      cells (CD16 + 56 positive cells) showed similar trend like CD3 and CD4 counts
      with significant differences in the mean cell counts between FACSCalibur, Cell
      Quest Pro (240 +/- 165 cells/microl), and FACSDiva (238 +/- 163 cells/microl)
      versus FACSCanto with higher NK cell counts (260 +/- 176 cells/microl).
      CONCLUSIONS: The enumeration of lymphocyte subsets was comparable between
      FACSCalibur, Cell Quest Pro, and FACSDiva, based analysis and it was
      significantly different than FACSCanto software based analysis. Our observations
      suggest that FACSDiva software should be preferred over the FACSCanto software
      for immunophenotyping on FACSCanto flow cytometer and the laboratories should
      report the instrument and software used for the specimen analysis while reporting
      immunophenotyping results.

PMID- 17226863
TI  - Flow cytometric immunphenotyping of epithelial cancer cells in effusions-
      technical considerations and pitfalls.
AB  - BACKGROUND: Data regarding the role of flow cytometry (FCM) in the
      characterization of malignant effusions are limited to date. In the present
      study, we optimized the conditions for FCM immunphenotyping of effusions using a
      four-color analysis and investigated aspects related to the advantages and
      limitations of this method in this setting. METHODS: FCM analysis optimization
      for the study of epithelial cells was undertaken using five carcinoma cell lines,
      and subsequently applied to malignant pleural and peritoneal effusions using
      antibodies against epithelial and mesothelial markers (Ber-EP4 and EMA), CD138,
      and integrin subunits. FCM of frozen versus fresh specimens and the performance
      of FCM compared to immunhistochemistry were evaluated. RESULTS: FCM optimization
      was achieved and applied to clinical specimens, with resulting detection of
      epithelial markers and adhesion molecules on cancer cells. Frozen clinical
      specimens and cell lines showed reduced CD138 expression compared to fresh
      specimens, with conservation of the remaining epitopes. FCM generally showed
      comparable performance to immunhistochemistry. CONCLUSIONS: FCM is an effective
      method for characterization of cancer cells in clinical effusion specimens in
      both the diagnostic and research setting, and is comparable to
      immunhistochemistry in terms of sensitivity and specificity, with the additional
      advantage of providing quantitative data. The majority of epitopes are conserved
      in frozen cells, but a minority may be lost, suggesting that the thorough testing
      of each antibody in both conditions is mandatory.

PMID- 17226864
TI  - Analyzing B cell chronic lymphocytic leukemia with Oncomark tubes on a FACSCanto.

PMID- 17226865
TI  - Ruthenium-Lewis acid catalyzed asymmetric Diels-Alder reactions between dienes
      and alpha,beta-unsaturated ketones.
AB  - The complex [Ru(Cp)(R,R-BIPHOP-F)(acetone)][SbF(6)], (R,R)-1 a, was used as
      catalyst for asymmetric Diels-Alder reactions between dienes (cyclopentadiene,
      methylcyclopentadiene, isoprene, 2,3-dimethylbutadiene) and alpha,beta
      unsaturated ketones (methyl vinyl ketone (MVK), ethyl vinyl ketone, divinyl
      ketone, alpha-bromovinyl methyl ketone and alpha-chlorovinyl methyl ketone). The
      cycloaddition products were obtained in yields of 50-90 % and with
      enantioselectivities up to 96 % ee. Ethyl vinyl ketone, divinyl ketone and the
      halogenated vinyl ketones worked best and their reactions with acyclic dienes
      consistently provided products with >90 % ee. alpha-Chlorovinyl methyl ketone
      performed better than alpha-bromovinyl methyl ketone. The reaction also provided
      a [4.3.1]bicyclic ring system in 95 % ee through an intramolecular cycloaddition
      reaction. Crystal structure determinations of [Ru(Cp)((S,S)-BIPHOP
      F)(mvk)][SbF(6)], (S,S)-1 b, and [Ru(Cp)((R,R)-Me(4)BIPHOP-F)(acrolein)][SbF(6)],
      (R,R)-2 b, provided the basis for a rationalization of the asymmetric induction.

PMID- 17226866
TI  - Stereoselective biocatalytic synthesis of (S)-2-hydroxy-2-methylbutyric acid via
      substrate engineering by using "thio-disguised" precursors and oxynitrilase
      catalysis.
AB  - 3-Tetrahydrothiophenone (4) and 4-phenylthiobutan-2-one (7) were used as masked 2
      butanone equivalents to give the corresponding cyanohydrins 5 (79 % yield, 91 %
      ee) and 8 (95 % yield, 96 % ee) in an enzymatic cyanohydrin reaction applying the
      hydroxynitrile lyase (HNL) from Hevea brasiliensis. After hydrolysis and
      desulphurisation the desired intermediate (S)-2-hydroxy-2-methylbutyric acid (10)
      was obtained with 99 % ee. Interestingly, when applying (R)-selective HNL from
      Prunus amygdalus again the (S)-cyanohydrin 5 was formed (62 % ee). The absolute
      configuration of 5 was verified by crystal structure determination of the
      corresponding hydrolysis derived carboxylate. The fact that both enzymes yield
      the same enantiomer was analysed and interpreted by molecular modelling
      calculations.

PMID- 17226867
TI  - Molecular factors responsible for the formation of the axially polar columnar
      mesophase Col(h)P(A).
AB  - The structure of hexacatenar bent-shape molecules has been systematically
      modified in order to determine the main molecular factors responsible for the
      appearance of the axially polar columnar mesophase. It was found that the
      stability of the polar phase is very sensitive to the subtle modifications of the
      molecular shape: the phase is solely preserved if the modification is made at the
      terminal parts of the mesogenic core, whilst any other modifications destabilize
      the phase. It can be concluded that the main factor driving the transition
      between the phase made of flat supramolecular discs and the axially polar phase
      made of the cone-like units is the ability to fulfill close packing conditions in
      order to eliminate voids between neighboring molecular rigid cores.

PMID- 17226868
TI  - Effect of cyanato, azido, carboxylato, and carbonato ligands on the formation of
      cobalt(II) polyoxometalates: characterization, magnetic, and electrochemical
      studies of multinuclear cobalt clusters.
AB  - Five Co(II) silicotungstate complexes are reported. The centrosymmetric
      heptanuclear compound K(20)[{(B-beta-SiW(9)O(33)(OH))(beta
      SiW(8)O(29)(OH)(2))Co(3)(H(2)O)}(2)Co(H(2)O)(2)]47 H(2)O (1) consists of two {(B
      beta-SiW(9)O(33)(OH))(beta-SiW(8)O(29)(OH)(2))Co(3)(H(2)O)} units connected by a
      {CoO(4)(H(2)O)(2)} group. In the chiral species K(7)[Co(1.5)(H(2)O)(7))][(gamma
      SiW(10)O(36))(beta-SiW(8)O(30)(OH))Co(4)(OH)(H(2)O)(7)]36 H(2)O (2), a {gamma
      SiW(10)O(36)} and a {beta-SiW(8)O(30)(OH)} unit enclose a mononuclear
      {CoO(4)(H(2)O)(2)} group and a {Co(3)O(7)(OH)(H(2)O)(5)} fragment. The two
      trinuclear Co(II) clusters present in 1 enclose a mu(4)-O atom, while in 2 a
      mu(3)-OH bridging group connects the three paramagnetic centers of the trinuclear
      unit, inducing significantly larger Co-L-Co (L=mu(4)-O (1), mu(3)-OH (2))
      bridging angles in 2 (theta(av(Co-L-Co))=99.1 degrees ) than in 1 (theta(av(Co-L
      Co))=92.8 degrees ). Weaker ferromagnetic interactions were found in 2 than in 1,
      in agreement with larger Co-L-Co angles in 2. The electrochemistry of 1 was
      studied in detail. The two chemically reversible redox couples observed in the
      positive potential domain were attributed to the redox processes of Co(II)
      centers, and indicated that two types of Co(II) centers in the structure were
      oxidized in separate waves. Redox activity of the seventh Co(II) center was not
      detected. Preliminary experiments indicated that 1 catalyzes the reduction of
      nitrite and NO. Remarkably, a reversible interaction exists with NO or related
      species. The hybrid tetranuclear complexes K(5)Na(3)[(A-alpha
      SiW(9)O(34))Co(4)(OH)(3)(CH(3)COO)(3)]18 H(2)O (3) and K(5)Na(3)[(A-alpha
      SiW(9)O(34))Co(4)(OH)(N(3))(2)(CH(3)COO)(3)]18 H(2)O (4) were characterized: in
      both, a tetrahedral {Co(4)(L(1))(L(2))(2)(CH(3)COO)(3)} (3: L(1)=L(2)=OH; 4:
      L(1)=OH, L(2)=N(3)) unit capped the [A-alpha-SiW(9)O(34)](10-) trivacant
      polyanion. The octanuclear complex K(8)Na(8)[(A-alpha
      SiW(9)O(34))(2)Co(8)(OH)(6)(H(2)O)(2)(CO(3))(3)]52 H(2)O (5), containing two
      {Co(4)O(9)(OH)(3)(H(2)O)} units, was also obtained. Compounds 2, 3, 4, and 5 were
      less stable than 1, but their partial electrochemical characterization was
      possible; the electronic effect expected for 3 and 4 was observed.

PMID- 17226869
TI  - Ferromagnetism in a new manganese-related Brownmillerite: La0.5Sr0.5MnO2.5.
AB  - The topotactic reduction of La0.5Sr0.5MnO3 leads to ordering of the anionic
      vacancies in the La0.5Sr0.5MnO2.5 composition. The isolated material, which is
      isostructural with Sr2Fe2O5, crystallises in the brownmillerite structural type
      with unit cell parameters a=0.54117(3), b=1.67608(12), c=0.54004(3) nm and space
      group Ibm2. Its microstructural characterisation by means of electron diffraction
      and high-resolution electron microscopy suggests a complex microstructure arising
      from the coherent intergrowth of different brownmillerite-type domains that show
      short-range ordering at the A sub-lattice. The layer structure of
      La0.5Sr0.5MnO2.5 leads to a double magnetic behaviour where a ferromagnetic two
      dimensional component is present.

PMID- 17226871
TI  - Self-assembly of an alkylated guanosine derivative into ordered supramolecular
      nanoribbons in solution and on solid surfaces.
AB  - We report on the synthesis and self-assembly of a guanosine derivative bearing an
      alkyloxy side group under different environmental conditions. This derivative was
      found to spontaneously form ordered supramolecular nanoribbons in which the
      individual nucleobases are interacting through H-bonds. In toluene and chloroform
      solutions the formation of gel-like liquid-crystalline phases was observed. Sub
      molecularly resolved scanning tunneling microscopic imaging of monolayers
      physisorbed at the graphite-solution interface revealed highly ordered two
      dimensional networks. The recorded intramolecular contrast can be ascribed to the
      electronic properties of the different moieties composing the molecule, as proven
      by quantum-chemical calculations. This self-assembly behavior is in excellent
      agreement with that of 5'-O-acylated guanosines, which are also characterized by
      a self-assembled motif of guanosines that resembles parallel ribbons. Therefore,
      for guanosine derivatives (without sterically demanding groups on the guanine
      base) the formation of supramolecular nanoribbons in solution, in the solid
      state, and on flat surfaces is universal. This result is truly important in view
      of the electronic properties of these supramolecular anisotropic architectures
      and thus for potential applications in the fields of nano- and opto-electronics.

PMID- 17226870
TI  - Synthesis, ionisation potentials and electron affinities of hexaazatrinaphthylene
      derivatives.
AB  - Several hexaazatrinaphthylene derivatives and a tris(thieno)hexaazatriphenylene
      derivative have been synthesised by reaction of the appropriate diamines with
      hexaketocyclohexane. The crystal structure of 2,3,8,9,14,15-hexachloro
      5,6,11,12,17,18-hexaazatrinaphthylene has been determined by X-ray diffraction;
      this reveals a molecular structure in good agreement with that predicted by
      density functional theory (DFT) calculations and pi-stacking with an average
      spacing between adjacent molecular planes of 3.18 A. Solid-state ionisation
      potentials have been measured by using UV photoelectron spectroscopy and fall in
      the range of 5.99 to 7.76 eV, whereas solid-state electron affinities, measured
      using inverse photoelectron spectroscopy, vary in the range -2.65 to -4.59 eV.
      The most easily reduced example is a tris(thieno)hexaazatriphenylene substituted
      with bis(trifluoromethyl)phenyl groups; DFT calculations suggest that the highly
      exothermic electron affinity is due both to the replacement of the outermost
      phenylene rings of hexaazatrinaphthylene with thieno groups and to the presence
      of electron-withdrawing bis(trifluoromethyl)phenyl groups. The rather exothermic
      electron affinities, the potential for adopting pi-stacked structures and the low
      intramolecular reorganisation energies obtained by DFT calculations suggest that
      some of these molecules may be useful electron-transport materials.

PMID- 17226872
TI  - Neutron powder diffraction with (nat)Sm: crystal structures and magnetism of a
      binary samarium deuteride and a ternary samarium magnesium deuteride.
AB  - Binary SmH(3) (trigonal, a=656.7(3), c=680.1(3) pm, P$?bar 3$c1, Z=6), ternary
      SmMg2H7 (tetragonal, a=626.47(6), c=937.2(2) pm, P4(1)2(1)2, Z=4) and the
      corresponding deuterides SmD3 (a=653.9(1)m, c=676.7(2) pm) and SmMg2D7
      (a=624.10(1), c=934.81(2) pm) have been prepared by hydrogenation (deuteration)
      of elemental samarium and the Laves phase SmMg2, respectively, and investigated
      by X-ray and neutron powder diffraction and SQUID and vibration magnetometry. The
      problem of the enormous neutron absorption of the natural isotopic mixture
      (natSm) is circumvented by carefully choosing the neutron wavelength
      (approximately 50 pm) and the use of double-walled cylindrical sample holders and
      a high-intensity neutron diffractometer (D4c at ILL). SmD3 crystallises with a
      tysonite-type structure and has three independently ordered deuterium atom sites
      with trigonal-planar, trigonal-pyramidal and tetrahedral metal environments and
      Sm--D bond lengths in the range 220(1)-258(1) pm (average: 235 pm). SmMg2D7 is a
      new deuteride that crystallises with an LaMg2D7-type structure. It displays four
      fully occupied deuterium sites having triangular and tetrahedral metal
      environments and Sm--D bond lengths in the range 227.6(5)-246.8(8) pm (average:
      239 pm). These are the first samarium-deuterium bond lengths to be reported. Both
      deuterides are paramagnetic down to 2 K (SmD3: mueff=0.63(1) muB, thetap
      approximately -4 K; SmMg2D7: mueff=0.57(2) muB, thetap approximately -4 K). Their
      crystal structures and chemical and physical properties suggest mainly ionic
      bonding according to the limiting ionic formulae Sm3+(H-)3 and Sm3+(Mg2+)2(H-)7.

PMID- 17226874
TI  - Adsorption, diffusion and desorption of chlorine on and from rutile TiO2{110}: a
      theoretical investigation.
AB  - The adsorption, diffusion and desorption of chlorine on and from stoichiometric,
      reduced and partially reduced (defective) rutile TiO2{110} are investigated using
      ab initio density functional theory (DFT) calculations. Theoretical results are
      compared with experimental investigations, and microkinetic simulations based on
      DFT values are then used to verify the diffusion mechanisms assumed in the
      experimental investigations.

PMID- 17226873
TI  - Luminescent Eu(III) and Gd(III) trisbipyridine cryptates: experimental and
      theoretical study of the substituent effects.
AB  - Synthesis, absorption spectra and luminescebce properties of a series of
      lanthanide trisbipyridine cryptates Ln within R-Bpy x R-Bpy x R-Bpy, where Ln =
      Eu, Gd and R = H, COOH, COOCH3, CONH(CH2)2NH2 are described. Comparison of the
      unsubstituted parent compound with the substituted compounds shows that
      bipyridine substitution doesn't alter significantly the photophysical properties
      of the lanthanide cryptate. The absorption maximum is slightly red-shifted when
      three bipyridines are substituted, whereas substituting one bipyridines has a
      negligible effect on the absorption spectra. The experimental triplet state
      energy is between 21600 and 22 100 cm(-1) for the series of compounds and the
      luminescence lifetimes at 77 K are between 0.5 and 0.8 ms in HO2 and equal to 1.7
      ms in D2O. The experimental characterizations are completed by DFT and TD-DFT
      calculations to assess the ability of these approaches to predict absorption
      maxima, triplet state energies and structural parameters of lanthanide cryptates
      and to characterize the electronic structure of the excited states. The
      calculations on the unsubstituted parent and substituted compounds show that
      absorption maxima and lowest 3pipi* triplet state energies can be accurately
      determined from density functional theory (DFT) and time-dependent (TD) DFT
      calculations.

PMID- 17226875
TI  - Physico-chemical characterization of nanofiltration membranes.
AB  - This study presents a methodology for an in-depth characterization of six
      representative commercial nanofiltration membranes. Laboratory-made
      polyethersulfone membranes are included for reference. Besides the physical
      characterization [molecular weight cut-off (MWCO), surface charge, roughness and
      hydrophobicity], the membranes are also studied for their chemical composition
      [attenuated total reflectance Fourier spectroscopy (ATR-FTIR) and X-ray
      photoelectron spectroscopy (XPS)] and porosity [positron annihilation
      spectroscopy (PAS)]. The chemical characterization indicates that all membranes
      are composed of at least two different layers. The presence of an additional
      third layer is proved and studied for membranes with a polyamide top layer. PAS
      experiments, in combination with FIB (focused ion beam) images, show that these
      membranes also have a thinner and a less porous skin layer (upper part of the top
      layer). In the skin layer, two different pore sizes are observed for all
      commercial membranes: a pore size of 1.25-1.55 angstroms as well as a pore size
      of 3.20-3.95 angstroms (both depending on the membrane type). Thus, the pore size
      distribution in nanofiltration membranes is bimodal, in contrast to the generally
      accepted log-normal distribution. Although the pore sizes are rather similar for
      all commercial membranes, their pore volume fraction and hence their porosity
      differ significantly.

PMID- 17226876
TI  - One- and two-photon singlet oxygen generation with new fluorene-based
      photosensitizers.
AB  - The spectral properties of new fluorene-based photosensitizers for efficient
      singlet oxygen production are investigated at room temperature and 77 K. Two
      photon absorption (2PA) cross-sections of the fluorene derivatives are measured
      by the open aperture Z-scan method. The quantum yields of singlet oxygen
      generation under one- and two-photon excitation (phi(delta) and 2PAphi(delta),
      respectively), are determined by the direct measurement of singlet oxygen
      luminescence at approximately 1270 nm. The values of phi(delta) are independent
      of excitation wavelength, ranging from 0.6-0.9. The singlet oxygen quantum yields
      under two-photon excitation are 2PAphi(delta) approximately 1/2 phi(delta),
      indicating that the two processes exhibit the same mechanism of singlet oxygen
      production, independent of the mechanism of photon absorption.

PMID- 17226877
TI  - Synthesis of DNA-sequence-selective hairpin polyamide platinum complexes.
AB  - Two DNA-sequence-selective hairpin polyamide platinum(II) complexes, containing
      pyrrole and imidazole heterocyclic rings, have been synthesised by different
      methods. A six-ring complex, selective for (A/T)GGG(A/T) DNA sequences, was made
      by using solid-phase synthesis, whilst an eight-ring complex, selective for
      (A/T)CCTG(A/T) DNA sequences, was made by utilising standard wet chemistry. Solid
      phase synthesis resulted in a significantly higher yield, required less
      purification and is more efficient than the wet synthesis; as such, it is the
      preferred method for further work. The metal complexes were characterised by (1)H
      and (195)Pt NMR spectroscopy and ESI mass spectrometry. The two compounds provide
      a foundation for the synthesis of more complex molecules containing multiple
      hairpins and/or platinum groups.

PMID- 17226879
TI  - Chemical micropatterning of polycarbonate for site-specific peptide
      immobilization and biomolecular interactions.
AB  - Polycarbonate (PC) is a useful substrate for the preparation of microfluidic
      devices. Recently, its utility in bioanalysis has attracted much attention owing
      to the possibility of using compact discs as platforms for the high-throughput
      analysis of biomolecular interactions. In this article we report a novel method
      for the chemical micropatterning of polycarbonate based on the printing of
      functionalized silica nanoparticles. The semicarbazide groups present on the
      surface of the nanoparticles were used for the site-specific semicarbazone
      ligation of unprotected peptides derivatized by an alpha-oxoaldehyde group. The
      peptide micropatterns permitted the specific capture of antibodies. We report
      also the characterization of micropatterns on PC by using a wide-field optical
      imaging technique called Sarfus; this allows the detection of nm-thick films by
      using nonreflecting PC substrates and an optical microscope working with
      reflected differential interference contrast. The method described here is an
      easy way to modify polycarbonate surfaces for biomolecular interaction studies
      and should stimulate the use of PC for developing plastic biosensors.

PMID- 17226878
TI  - Droplets as microreactors for high-throughput biology.
AB  - Inspired by the principles of biological evolution, biologists--and others--have
      in recent decades harnessed the power of "natural" selection to sift through huge
      libraries of genes and find those with desirable properties. At the same time,
      the demand for high-throughput biochemical and genetic assays and screens has
      driven the development of increasingly miniaturised assay systems. An exciting
      synergy is now emerging between these two fields, whereby the tools of ultrahigh
      throughput screening promise to open up new directions in molecular engineering.

PMID- 17226880
TI  - [Os3(CO)6(PMe3)3](mu3-eta2:eta2:eta2-C60)[Re3(mu-H)3(CO)9]: a fullerene[60]
      coordinated to two different trinuclear clusters.

PMID- 17226881
TI  - Template synthesis of multishelled Cu2O hollow spheres with a single-crystalline
      shell wall.

PMID- 17226882
TI  - Formation of vesicular structures through the self-assembly of a flexible bis
      zwitterion in dimethyl sulfoxide.

PMID- 17226883
TI  - Luminescence detection of open-shell transition-metal ions by photoinduced
      electron transfer controlled by internal charge transfer of a receptor.

PMID- 17226885
TI  - Synthetic study towards azadirachtin: an efficient and stereoselective
      construction of the AB rings with full functionality.

PMID- 17226884
TI  - Chromium-carbyne complexes: intermediates for organic synthesis.

PMID- 17226886
TI  - Structures of RNA switches: insight into molecular recognition and tertiary
      structure.
AB  - RNA switches (riboswitches) have important functions in gene regulation. They
      comprise an aptamer domain, which is responsible for ligand binding, and an
      expression platform that transmits the ligand-binding state of the aptamer domain
      through a conformational change. Riboswitches can regulate gene expression either
      at the level of transcription or translation, and it has been proposed that
      riboswitch mechanisms are even used to regulate the processing of mRNA. This
      Minireview summarizes the current understanding of the structures and mode of
      action of RNA switches, with particular focus on secondary and tertiary
      interactions, which stabilize the global RNA structure and thus determine the
      function of the aptamer domain.

PMID- 17226887
TI  - Characterization of the enzyme BtrD from Bacillus circulans and revision of its
      functional assignment in the biosynthesis of butirosin.

PMID- 17226888
TI  - The oxorhenium(VII)-catalyzed direct condensation of phosphoric acid with an
      alcohol.

PMID- 17226890
TI  - Catalysis by gold(I) and gold(III): a parallelism between homo- and heterogeneous
      catalysts for copper-free Sonogashira cross-coupling reactions.

PMID- 17226889
TI  - Remarkably simple fabrication of superhydrophobic surfaces using electroless
      galvanic deposition.

PMID- 17226891
TI  - Crystal-state 3D-structural characterization of novel, Aib-based, turn and
      helical peptides.
AB  - The crystal-state conformations of the hexapeptide amide Pht-(Aib)(6)-NH
      C(CH(3))(2)-O-OtBu (7), the hexapeptide Ac-L-aIle-(Aib)(5)-OtBu (6), the
      pentapeptide Z-(Aib)(3)-L-Glu(OtBu)-Aib-O-(CH(2))(2)-(1)Nap (5), the
      tetrapeptides Z-(Aib)(2)-L-His(N(tau)-Trt)-Aib-OMe (4 I) and Z-(Aib)(2)-L-Nva-Aib
      OtBu (4 II), the tripeptide Pyr-(Aib)(3)-OtBu (3 I), the dipeptide amides Pyr
      (Aib)(2)-(4)NH-TEMPO (3 II) and Piv-(Aib)(2)-NH-C(CH(3))(2)-O-OtBu (3 III), and
      the dipeptides Pht-Aib-betaAc(6)c-OtBu (2 I), Pht-Aib-NH-C(CH(3))(2)-O-OtBu (2
      II) and Boc-gGly-mAib-OH (2 III) have been determined by X-ray diffraction
      analyses. All peptides investigated are characterized by one or more turn/helix
      forming Aib residues. Except the three short dipeptides, all are folded into
      C==O...H--N intramolecularly H-bonded 3(10)-helices, or into various types of
      beta-turns. In the structure of 6, two independent molecules of opposite screw
      sense were observed in the asymmetric unit, generating diastereomeric 3(10)
      helices.

PMID- 17226892
TI  - Triterpenoids from Eugenia grandis: structure elucidation by NMR spectroscopy.
AB  - A new pentacyclic triterpenoid, 2alpha,3beta-dihydroxylup-12-en-28-oic acid (1)
      and a rarely encountered pentacyclic triterpenoid, 3beta-hydroxylup-12-en-28-oic
      acid (2), together with five known compounds, friedelin (3), 3beta-friedelinol
      (4), betulinic acid (5), oleanolic acid (6) and beta-sitosterol (7) were isolated
      from the chloroform extract of stem bark of Eugenia grandis (Syn: Syzygium
      grande). The structure and stereochemistry of the new compound (1) and the rarely
      encountered compound (2) were established by 1D and 2D NMR spectroscopic
      techniques. All the above isolated compounds from this plant are reported for the
      first time.

PMID- 17226894
TI  - Giving equality of opportunity a fair innings.

PMID- 17226895
TI  - Role of endosonography in non-malignant pancreatic diseases.
AB  - Endoscopic ultrasound (EUS) has emerged as a valuable tool in the evaluation of
      benign and malignant pancreatic diseases. The ability to obtain high quality
      images and perform fine-needle aspiration (FNA) has led EUS to become the
      diagnostic test of choice when evaluating the pancreas. This article will review
      the role of EUS in benign pancreatic diseases.

PMID- 17226896
TI  - Pancreatitis-associated protein: from a lectin to an anti-inflammatory cytokine.
AB  - Pancreatitis-associated protein (PAP) was discovered in the pancreatic juice of
      rats with acute pancreatitis. PAP is a 16 kDa secretory protein structurally
      related to the C-type lectins although classical lectin-related function has not
      been reported yet. Then, it was demonstrated that PAP expression may be activated
      in some tissues in a constitutive or injury- and inflammation-induced manner.
      More recently, it has been found that PAP acts as an anti-inflammatory factor in
      vitro and in vivo. PAP expression can be induced by several pro- and anti
      inflammatory cytokines and by itself through a JAK/STAT3-dependent pathway. PAP
      is able to activate the expression of the anti-inflammatory factor SOCS3 through
      the JAK/STAT3-dependent pathway. The JAK/STAT3/SOCS3 pathway seems to be a common
      point between PAP and several cytokines. Therefore, it is reasonable to propose
      that PAP is a new anti-inflammatory cytokine.

PMID- 17226900
TI  - Importance of performance status for treatment outcome in advanced pancreatic
      cancer.
AB  - Despite progress in the treatment of advanced and metastatic pancreatic cancer
      (PC), the outcome of this disease remains dismal for the majority of patients.
      Given the moderate efficacy of treatment, prognostic factors may help to guide
      treatment decisions. Several trials identified baseline performance status as an
      important prognostic factor for survival. Unfit patients with a Karnofsky
      performance status (KPS) below 70% only have a marginal benefit from chemotherapy
      with gemcitabine (Gem) and may often benefit more from optimal supportive care.
      Once, however, the decision is taken to apply chemotherapy, KPS may be used to
      select either mono- or combination chemotherapy. Patients with a good performance
      status (KPS = 90%-100%) may have a significant and clinically relevant survival
      benefit from combination chemotherapy. By contrast, patients with a poor
      performance status (KPS < or = 80%) have no advantage from intensified therapy
      and should rather receive single-agent treatment.

PMID- 17226899
TI  - Differential diagnosis between functional and organic intestinal disorders: is
      there a role for non-invasive tests?
AB  - Abdominal pain and bowel habits alterations are common symptoms in the general
      population. The investigation to differentiate organic from functional bowel
      disorders represents a considerable burden both for patients and public health
      service. The selection of patients who should undergo endoscopic and/or
      radiological procedures is one of the key points of the diagnostic process, which
      should avoid the abuse of invasive and expensive tests as well as the
      underestimation of potentially harmful diseases. Over the coming years,
      clinicians and researchers will be challenged to develop strategies to increase
      the patient's compliance and to reduce the economic and social costs of the
      intestinal diseases.

PMID- 17226897
TI  - Early diabetic neuropathy: triggers and mechanisms.
AB  - Peripheral neuropathy, and specifically distal peripheral neuropathy (DPN), is
      one of the most frequent and troublesome complications of diabetes mellitus. It
      is the major reason for morbidity and mortality among diabetic patients. It is
      also frequently associated with debilitating pain. Unfortunately, our knowledge
      of the natural history and pathogenesis of this disease remains limited. For a
      long time hyperglycemia was viewed as a major, if not the sole factor,
      responsible for all symptomatic presentations of DPN. Multiple clinical
      observations and animal studies supported this view. The control of blood glucose
      as an obligatory step of therapy to delay or reverse DPN is no longer an arguable
      issue. However, while supporting evidence for the glycemic hypothesis has
      accumulated, multiple controversies accumulated as well. It is obvious now that
      DPN cannot be fully understood without considering factors besides hyperglycemia.
      Some symptoms of DPN may develop with little, if any, correlation with the
      glycemic status of a patient. It is also clear that identification of these
      putative non-glycemic mechanisms of DPN is of utmost importance for our
      understanding of failures with existing treatments and for the development of new
      approaches for diagnosis and therapy of DPN. In this work we will review the
      strengths and weaknesses of the glycemic hypothesis, focusing on clinical and
      animal data and on the pathogenesis of early stages and triggers of DPN other
      than hyperglycemia.

PMID- 17226898
TI  - Advances in small animal mesentery models for in vivo flow cytometry, dynamic
      microscopy, and drug screening.
AB  - Using animal mesentery with intravital optical microscopy is a well-established
      experimental model for studying blood and lymph microcirculation in vivo. Recent
      advances in cell biology and optical techniques provide the basis for extending
      this model for new applications, which should generate significantly improved
      experimental data. This review summarizes the achievements in this specific area,
      including in vivo label-free blood and lymph photothermal flow cytometry, super
      sensitive fluorescence image cytometry, light scattering and speckle flow
      cytometry, microvessel dynamic microscopy, infrared (IR) angiography, and high
      speed imaging of individual cells in fast flow. The capabilities of these
      techniques, using the rat mesentery model, were demonstrated in various studies;
      e.g., real-time quantitative detection of circulating and migrating individual
      blood and cancer cells, studies on vascular dynamics with a focus on lymphatics
      under normal conditions and under different interventions (e.g. lasers, drugs,
      nicotine), assessment of lymphatic disturbances from experimental lymphedema,
      monitoring cell traffic between blood and lymph systems, and high-speed imaging
      of cell transient deformability in flow. In particular, the obtained results
      demonstrated that individual cell transportation in living organisms depends on
      cell type (e.g., normal blood or leukemic cells), the cellos functional state
      (e.g., live, apoptotic, or necrotic), and the functional status of the organism.
      Possible future applications, including in vivo early diagnosis and prevention of
      disease, monitoring immune response and apoptosis, chemo- and radio-sensitivity
      tests, and drug screening, are also discussed.

PMID- 17226901
TI  - Interferon-alpha response in chronic hepatitis B-transfected HepG2.2.15 cells is
      partially restored by lamivudine treatment.
AB  - AIM: To characterize the IFN-response and its modulation by the antiviral
      compound lamivudine in HBV-transfected HepG2.2.15 cells. METHODS: HepG2.2.15 and
      HepG2 cells were stimulated with various concentrations of IFN-alpha2a in the
      presence or absence of lamivudine. Then, total RNA was extracted and analysed by
      customised cDNA arrays and northern blot for interferon-inducible genes (ISGs).
      In addition, cellular proteins were extracted for EMSA and western blot. HBV
      replication was assessed by southern blot or ELISAs for HBsAg and HBeAg. RESULTS:
      Two genes (MxA, Cig5) with completely abolished and 4 genes (IFITM1, -2, -3, and
      6-16) with partially reduced IFN-responses were identified in HepG2.2.15 cells.
      In 2 genes (IFITM1, 6-16), the response to IFN-alpha could be restored by
      treatment with lamivudine. This effect could not be explained by a direct
      modulation of the Jak/Stat signalling pathway since EMSA and western blot
      experiments revealed no suppression of Stat1 activation and ISGF3 formation after
      stimulation with IFN-alpha in HepG2.2.15 compared to HepG2 cells. CONCLUSION:
      These results are consistent with the assumption that chronic hepatitis B may
      specifically modulate the cellular response to IFN by a selective blockage of
      some ISGs. Antiviral treatment with lamivudine may partially restore ISG
      expression by reducing HBV gene expression and replication.

PMID- 17226902
TI  - Correlation between in vitro and in vivo immunomodulatory properties of lactic
      acid bacteria.
AB  - AIM: To investigate the correlation between in vitro and in vivo immunomodulation
      potential of the probiotic strain and its ability to prevent experimental colitis
      in mice. METHODS: In vitro immunomodulation was assessed by measuring interleukin
      (IL)-12p70, IL-10, tumor necrosis factor alpha (TNFalpha) and interferon gamma
      (IFNgamma) release by human peripheral blood mononuclear cells (PBMCs) after 24 h
      stimulation with 13 live bacterial strains. A murine model of acute TNBS-colitis
      was next used to evaluate the prophylactic protective capacity of the same set of
      strains. RESULTS: A strain-specific in vivo protection was observed. The strains
      displaying an in vitro potential to induce higher levels of the anti-inflammatory
      cytokine IL-10 and lower levels of the inflammatory cytokine IL-12, offered the
      best protection in the in vivo colitis model. In contrast, strains leading to a
      low IL-10/IL-12 cytokine ratio could not significantly attenuate colitis
      symptoms. CONCLUSION: These results show that we could predict the in vivo
      protective capacity of the studied lactic acid bacteria (LAB) based on the
      cytokine profile we established in vitro. The PBMC-based assay we used may thus
      serve as a useful primary indicator to narrow down the number of candidate
      strains to be tested in murine models for their anti-inflammatory potential.

PMID- 17226903
TI  - Rescue of the albino phenotype by introducing a functional tyrosinase minigene
      into Kunming albino mice.
AB  - AIM: To use the tyrosinase minigene as a visual marker to perform microinjection
      training and improve the techniques related with transgene to greatly elevate the
      efficiency of gene transfer. METHODS: A mouse tyrosinase minigene, i.e., TyBS, in
      which the 2.25-kb authentic genomic 5' non-coding flanking sequence of mouse
      tyrosinase was fused to a mouse tyrosinase cDNA, was introduced into the
      fertilized eggs of outbred Kunming albino mice. RESULTS: Of the 11 animals that
      developed from the injected eggs, two mice (P1 and #8) exhibited pigmented hair
      (P1) and eyes (P1 and #8), as confirmed by PCR analysis for the tyrosinase
      minigene integrated into the genome. When founder P1 was bred to Kunming male
      mouse, six progeny out of 11 offspring inherited the transgene and the pigmented
      eye phenotype. CONCLUSION: Taken together, these results suggest that this
      minigene encodes the active tyrosinase protein and that its 5' flanking region
      contains the sequences regulating the expression of mouse tyrosinase gene as
      expected. We have rescued the albino phenotype by introduction and expression of
      a functional tyrosinase minigene in the Kunming albino mouse and the transgene
      can be passed to subsequent generation. These findings also indicate that TyBS
      can be a useful visual marker gene in the co-transgenic experiments.

PMID- 17226904
TI  - Antiproliferation and apoptosis induction of paeonol in HepG2 cells.
AB  - AIM: To investigate the antiproliferative effect of paeonol (Pae) used alone or
      in combination with chemotherapeutic agents [cisplatin (CDDP), doxorubicin (DOX)
      and 5-fluorouracil (5-FU)] on human hepatoma cell line HepG2 and the possible
      mechanisms. METHODS: The cytotoxic effect of drugs on HepG2 cells was measured by
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
      Morphologic changes were observed by acridine orange (AO) fluorescence staining.
      Cell cycle and apoptosis rate were detected by flow cytometry (FCM). Drug-drug
      interactions were analyzed by the coefficient of drug interaction (CDI). RESULTS:
      Pae (7.81-250 mg/L) had an inhibitory effect on the proliferation of HepG2 cells
      in a dose-dependent manner, with the IC50 value of (104.77 +/- 7.28) mg/L. AO
      fluorescence staining and FCM assays showed that Pae induced apoptosis and
      arrested cell cycle at S phase in HepG2 cells. Further, different extent
      synergisms were observed when Pae (15.63, 31.25, 62.5 mg/L) was combined with
      CDDP (0.31-2.5 mg/L), DOX (0.16-1.25 mg/L), or 5-FU (12.5-100 mg/L) at
      appropriate concentrations. The IC50 value of the three drugs decreased
      dramatically when combined with Pae (P < 0.01). Of the three different
      combinations, the sensitivity of cells to drugs was considerably different.
      CONCLUSION: Pae had a significant growth-inhibitory effect on the human hepatoma
      cell line HepG2, which may be related to apoptosis induction and cell cycle
      arrest. It also can enhance the cytotoxicity of chemotherapeutic agents on HepG2
      cells, and the S phase arrest induced by Pae may be one of the mechanisms of
      these interactions.

PMID- 17226905
TI  - Detection of disseminated pancreatic cells by amplification of cytokeratin-19
      with quantitative RT-PCR in blood, bone marrow and peritoneal lavage of
      pancreatic carcinoma patients.
AB  - AIM: To evaluate the diagnostic potential of cytokeratin-19 (CK-19) mRNA for the
      detection of disseminated tumor cells in blood, bone marrow and peritoneal lavage
      in patients with ductal adenocarcinoma of the pancreas. METHODS: Sixty-eight
      patients with pancreatic cancer (n = 37), chronic pancreatitis (n = 16), and non
      pancreatic benign surgical diseases (n = 15, control group) were included in the
      study. Venous blood was taken preoperatively, intraoperatively and at
      postoperative d 1 and 10. Preoperative bone marrow aspirates and peritoneal
      lavage taken before mobilization of the tumor were analyzed. All samples were
      evaluated for disseminated tumor cells by CK-19-specific nested-PCR and
      quantitative fluorogenic RT-PCR. RESULTS: CK-19 mRNA expression was increased in
      24 (64%) blood samples and 11 (30%) of the peritoneal lavage samples in the
      patients with pancreatic cancer. In 15 (40%) of the patients with pancreatic
      cancer, disseminated tumor cells were detected in venous blood and bone marrow
      and/or peritoneal lavage. In the peritoneal lavage, the detection rates were
      correlated with the tumor size and the tumor differentiation. CK-19 levels were
      increased in pT3/T4 and moderately/poorly differentiated tumors (G2/G3).
      Pancreatic cancer patients with at least one CK-19 mRNA-positive sample showed a
      trend towards shorter survival. Pancreatic cancer patients showed significantly
      increased detection rates of disseminated tumor cells in blood and peritoneal
      lavage compared to the controls and the patients with chronic pancreatitis.
      CONCLUSION: Disseminated tumor cells can be detected in patients with pancreatic
      ductal adenocarcinoma by CK-19 fluorogenic RT-PCR. In peritoneal lavage,
      detection rate is correlated with tumor stage and differentiation. In the
      clinical use, CK-19 is suitable for the distinction between malignant and benign
      pancreatic disease in combination with other tumor-specific markers.

PMID- 17226906
TI  - Efficacy of long term cyclic administration of the poorly absorbed antibiotic
      Rifaximin in symptomatic, uncomplicated colonic diverticular disease.
AB  - AIM: To comparatively evaluate the long term efficacy of Rifaximin and dietary
      fibers in reducing symptoms and/or complication frequency in symptomatic,
      uncomplicated diverticular disease. METHODS: 307 patients (118 males, 189
      females, age range: 40-80 years) were enrolled in the study and randomly assigned
      to: Rifaximin (400 mg bid for 7 d every month) plus dietary fiber supplementation
      (at least 20 gr/d) or dietary fiber supplementation alone. The study duration was
      24 mo; both clinical examination and symptoms' questionnaire were performed every
      two months. RESULTS: Both treatments reduced symptom frequency, but Rifaximin at
      a greater extent, when compared to basal values. Symptomatic score declined
      during both treatments, but a greater reduction was evident in the Rifaximin
      group (6.4 +/- 2.8 and 6.2 +/- 2.6 at enrollment, P = NS, 1.0 +/- 0.7 and 2.4 +/-
      1.7 after 24 mo, P < 0.001, respectively). Probability of symptom reduction was
      higher and complication frequency lower (Kaplan-Meyer method) in the Rifaximin
      group (P < 0.0001 and 0.028, respectively). CONCLUSION: In patients with
      symptomatic, uncomplicated diverticular disease, cyclic administration of
      Rifaximin plus dietary fiber supplementation is more effective in reducing both
      symptom and complication frequency than simple dietary fiber supplementation.
      Long term administration of the poorly absorbed antibiotic Rifaximin is safe and
      well tolerated by the patients, confirming the usefulness of this therapeutic
      strategy in the overall management of diverticular disease.

PMID- 17226908
TI  - Role of ciprofloxacin in patients with cholestasis after endoscopic retrograde
      cholangiopancreatography.
AB  - AIM: To determine the role of ciprofloxacin in reducing cholangitis in
      cholestatic patients with adequate biliary drainage after endoscopic retrograde
      cholangiopancreatography (ERCP). METHODS: A randomized, controlled trial was
      performed in 48 cholestatic patients at Rajavithi Hospital (Tertiary Referral
      Center for ERCP: 600 cases per year). All the 48 patients received 200 mg
      ciprofloxacin intravenous injection for 30 min before starting any procedures,
      and then were randomly divided in two groups. Twenty-two patients in study group
      continually received ciprofloxacin until 48 h after ERCP. Causes of biliary
      obstruction, bacteriology of bile and blood (in cholangitis) and clinical
      cholangitis were recorded. RESULTS: Forty-eight patients were enrolled and
      divided into continuous ciprofloxacin treatment group (n = 22) and discontinuous
      ciprofloxacin treatment group (n = 26). During ERCP, stones were found in 22
      patients, malignant diseases in 24 patients and other pathologic lesions in 5
      patients. One (4.5%) of the 22 patients who received ciprofloxacin and 2 (6.3%)
      of the 26 patients who discontinued ciprofloxacin after ERCP developed
      cholangitis (relative risk = 0.71; 95% CI = 0.14-3.65; P = 0.88). Bacterobilia
      was found in 27 (56.3%) out of 48 patients. E. coli and Streptococcus viridans
      were the most common organisms. CONCLUSION: Continual use of ciprofloxacin in
      patients with cholestasis after adequate biliary drainage procedures plays no
      role in reducing cholangitis.

PMID- 17226907
TI  - Proximal gastric motility in critically ill patients with type 2 diabetes
      mellitus.
AB  - AIM: To investigate the proximal gastric motor response to duodenal nutrients in
      critically ill patients with long-standing type 2 diabetes mellitus. METHODS:
      Proximal gastric motility was assessed (using a barostat) in 10 critically ill
      patients with type 2 diabetes mellitus (59 +/- 3 years) during two 60-min
      duodenal infusions of Ensure (1 and 2 kcal/min), in random order, separated by 2
      h fasting. Data were compared with 15 non-diabetic critically ill patients (48 +/
      5 years) and 10 healthy volunteers (28 +/- 3 years). RESULTS: Baseline proximal
      gastric volumes were similar between the three groups. In diabetic patients,
      proximal gastric relaxation during 1 kcal/min nutrient infusion was similar to
      non-diabetic patients and healthy controls. In contrast, relaxation during 2
      kcal/min infusion was initially reduced in diabetic patients (P < 0.05) but
      increased to a level similar to healthy humans, unlike non-diabetic patients
      where relaxation was impaired throughout the infusion. Duodenal nutrient
      stimulation reduced the fundic wave frequency in a dose-dependent fashion in both
      the critically ill diabetic patients and healthy subjects, but not in critically
      ill patients without diabetes. Fundic wave frequency in diabetic patients and
      healthy subjects was greater than in non-diabetic patients. CONCLUSION: In
      patients with diabetes mellitus, proximal gastric motility is less disturbed than
      non-diabetic patients during critical illness, suggesting that these patients may
      not be at greater risk of delayed gastric emptying.

PMID- 17226909
TI  - Twenty-four hour intra-arterial infusion of 5-fluorouracil, cisplatin, and
      leucovorin is more effective than 6-hour infusion for advanced hepatocellular
      carcinoma.
AB  - AIM: To evaluate the time dependence of intra-arterial 5-fluorouracil (5-FU)
      therapy for advanced hepatocellular carcinoma (aHCC). METHODS: Thirty-seven adult
      Japanese patients who had aHCC and liver cirrhosis were treated with combined
      intra-arterial 5-FU, cisplatin (CDDP), and leucovorin (LV). The Japan Integrated
      Staging score (JIS score) of each patient was 3 or more. The patients were
      divided into two groups, after which the 15 patients in group S were treated with
      6-h infusion chemotherapy (LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/m2
      per 4 h) and the 22 patients in group L were treated with 24-h infusion
      chemotherapy (LV at 12 mg/h, CDDP at 10 mg/h, and 5-FU at 250 mg/ m2 per 22 h).
      Continuous infusion chemotherapy was performed via the proper hepatic artery
      every 5 d for 4 wk using an implanted drug reservoir. RESULTS: The percentages of
      patients with a partial response after 4 wk of chemotherapy were 6.7% in group S
      and 31.8% in group L. The survival of group L was significantly better than that
      of group S, with the median survival time being 496 d in group L and 226 d in
      group S (P < 0.05). CONCLUSION: Continuous 24-h intra-arterial infusion is more
      effective for aHCC and can markedly prolong survival time as compared to 6-h
      infusion.

PMID- 17226910
TI  - Totally laparoscopic trans-hiatal gastroesophagectomy for benign diseases of the
      esophago-gastric junction.
AB  - AIM: To prospectively present our initial experience with totally laparoscopic
      transhiatal esophagogastrectomies for benign diseases of the cardia and distal
      esophagus. METHODS: Laparoscopic gastric mobilization and tubularization combined
      with transhiatal esophageal dissection and intrathoracic esophagogastric
      anastomosis accomplished by a circular stapler was done in 3 patients. There were
      2 females and 1 male patient with a mean age of 73 +/- 5 years. RESULTS: Two
      patients were operated on due to benign stromal tumor of the cardia and one
      patient had severe oesophageal peptic stenosis. Mean blood loss was 47 +/- 15 mL
      and mean operating time was 130 +/- 10 min. There were no cases that required
      conversion to laparotomy. All patients were extubated immediately after surgery.
      Soft diet intake and ambulation times were 5.1 +/- 0.4 d and 2.6 +/- 0.6 d,
      respectively. There were no intraoperative and postoperative complications and
      there were no perioperative deaths. The average length of hospital stay was 9.3
      +/- 3 d. All procedures were curative and all resected margins were tumor free.
      The mean number of retrieved lymph nodes was 18 +/- 8. CONCLUSION: Laparoscopic
      transhiatal esophago-gastrectomy for benign lesions has good effects and proves
      feasible and safe.

PMID- 17226911
TI  - Impact of endoscopic ultrasound-guided fine needle biopsy for diagnosis of
      pancreatic masses.
AB  - AIM: To evaluate the diagnostic accuracy of histological evaluation of pancreatic
      tissue samples obtained by a modified method for recovering and processing the
      endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) material in the
      differential diagnosis of pancreatic solid masses. METHODS: Sixty-two consecutive
      patients with pancreatic masses were prospectively studied. EUS was performed by
      the linear scanning Pentax FG-38UX echoendoscope. Three FNAs (22G needle) were
      carried out during each procedure. The materials obtained with first and second
      punctures were processed for cytological study. Materials of the third puncture
      were recovered into 10% formol solution by careful injection of saline solution
      through the needle, and processed for histological study. RESULTS: Length of the
      core specimen obtained for histological analysis was 6.5 +/- 5.3 mm (range 1-22
      mm). Cytological and histological samples were considered as adequate in 51
      (82.3%) and 52 cases (83.9%), respectively. Overall sensitivity of both
      pancreatic cytology and histology for diagnosis of malignancy was 68.4%. Contrary
      to cytology, histology was able to diagnose tumours other than adenocarcinomas,
      and all cases of inflammatory masses. Combination of cytology and histology
      allowed obtaining an adequate sample in 56 cases (90.3%), with a global
      sensitivity of 84.21%, specificity of 100% and an overall accuracy of 90.32%. The
      complication rate was 1.6%. CONCLUSION: Adequate pancreatic core specimens for
      histological examination can be obtained by EUS-guided FNA. This technique is
      mainly useful for the diagnosis of different types of pancreatic tumours and
      evaluation of benign diseases.

PMID- 17226912
TI  - Immunogenicity of recombinant hepatitis B virus vaccine in patients with and
      without chronic hepatitis C virus infection: a case-control study.
AB  - AIM: To compare the response of standard hepatitis B virus (HBV) vaccination
      between patients with chronic hepatitis C virus (HCV) infection and healthy
      individuals. METHODS: This is a prospective case-control study. A total of 38
      patients with chronic HCV infection and 40 healthy controls were included.
      Vaccination was performed by injection of 20 microg recombinant HBsAg into the
      deltoid muscle at mo 0, 1 and 6. Anti-HBs concentration was determined 3 mo after
      the last dose and compared between the two groups. The response pattern was
      characterized as (1) high-response when the anti-HBs antibody titer was > 100
      IU/L, (2) low-response when the titer was 10-100 IU/L and (3) no-response when
      the titer was < 10 IU/L. RESULTS: In the patient group, there were 10/38 (26.3%)
      non-responders, 8/38 (21.1%) low-responders and 20/38 (52.6%) high-responders.
      The corresponding values in the control group were 2/40 (5.0%), 7/40 (17.5%) and
      31/40 (77.5%), respectively. The response pattern was statistically different
      between the two groups. In multivariate analysis, smoking was a significant
      confounder, while HCV infection lost its significant correlation with lower
      antibody response. CONCLUSION: Patients with chronic HCV infection tend to
      respond weakly to HBV vaccination compared to healthy individuals, though this
      correlation is not independent according to multivariate analysis.

PMID- 17226913
TI  - Ginkgo biloba extract (EGb 761) attenuates lung injury induced by intestinal
      ischemia/reperfusion in rats: roles of oxidative stress and nitric oxide.
AB  - AIM: To investigate the effect of ginkgo biloba extract (EGb 761) on lung injury
      induced by intestinal ischemia/reperfusion (II/R). METHODS: The rat model of II/R
      injury was produced by clamping the superior mesenteric artery for 60 min
      followed by reperfusion for 180 min. The rats were randomly allocated into sham,
      II/R, and EGb + II/R groups. In EGb + II/R group, EGb 761 (100 mg/kg per day) was
      given via a gastric tube for 7 consecutive days prior to surgery. Rats in II/R
      and sham groups were treated with equal volumes of the vehicle of EGb 761. Lung
      injury was assessed by light microscopy, wet-to-dry lung weight ratio (W/D) and
      pulmonary permeability index (PPI). The levels of malondialdehyde (MDA) and
      nitrite/nitrate (NO2(-)/NO3(-)), as well as the activities of superoxide
      dismutase (SOD) and myeloperoxidase (MPO) were examined. Western blot was used to
      determine the expression of inducible nitric oxide synthase (iNOS). RESULTS: EGb
      761 markedly improved mean arterial pressure and attenuated lung injury,
      manifested by the improvement of histological changes and significant decreases
      of pulmonary W/D and PPI (P < 0.05 or 0.01). Moreover, EGb 761 markedly increased
      SOD activity, reduced MDA levels and MPO activity, and suppressed NO generation
      accompanied by down-regulation of iNOS expression (P < 0.05 or 0.01). CONCLUSION:
      The results indicate that EGb 761 has a protective effect on lung injury induced
      by II/R, which may be related to its antioxidant property and suppressions of
      neutrophil accumulation and iNOS-induced NO generation. EGb 761 seems to be an
      effective therapeutic agent for critically ill patients with respiratory failure
      related to II/R.

PMID- 17226915
TI  - Jejuno-jejunal invagination due to intestinal melanoma.
AB  - Cutaneous melanoma is one of the most studied neoplastic lesions in biology and
      clinical oncology. It has been well documented that this type of neoplasm
      presents a high metastatic rate, and is able to involve nearly every tissue. Non
      cutaneous melanoma represents an unusual pattern of melanoma, and the small
      intestine is an uncommon anatomic localization. Herein we report an extremely
      rare clinical case of a young woman affected by a bleeding jejunal melanoma,
      whose early clinical presentation was an intestinal invagination.

PMID- 17226914
TI  - Are heat stroke and physical exhaustion underestimated causes of acute hepatic
      failure?
AB  - While cardiopulmonary symptoms are common in patients undergoing classical or,
      due to physical exercise, exertional heat stroke, the failure of other organs is
      a rarely described phenomenon. Here we present two cases of acute hepatic
      failure, one due to classic heat shock, while the other occurred while the
      patient was doing a marathon-type running. Both cases presented with very high
      transaminases and significantly elevated international normalized ratio (INR). No
      other causes for liver failure could be identified but physical exhaustion and
      hyperthermia.

PMID- 17226916
TI  - An unusual cause of cholecystitis: heterotopic pancreatic tissue in the
      gallbladder.
AB  - Gallbladder localization of heterotopic pancreas (HP) is uncommon and very rarely
      gives rise to symptoms. Herein we report a case of HP found in the gallbladder
      neck presented with signs and symptoms of cholecystitis. The patient was a 40
      year old male, suffering from epigastric pain, abdominal fullness and fever. On
      physical examination, the right upper abdomen was tender with a positive Murphy's
      sign. Ultrasonographic examination showed a hydropic gallbladder without stones
      and he underwent a cholecystectomy. Pathological examination revealed an
      intramural nodule (9 mm) in the neck region which is consisted of acini, ducts
      and islet cells of an aberrant pancreatic tissue. Although HP is encountered
      rarely in the gallbladder and is found incidentally during pathological studies,
      this case emphasizes that HP might cause symptoms and present clinically as
      cholecystitis. For this reason, in patients presenting with symptomatic
      gallbladder diseases, including cholecystitis without any other pathology, HP
      should be taken into consideration before it is diagnosed as "idiopathic".

PMID- 17226917
TI  - A case of interstitial pneumonitis in a patient with ulcerative colitis treated
      with azathioprine.
AB  - The early hypersensitivity reaction and late bone marrow depression are well
      known side-effects of azathioprine, whereas interstitial pneumonia is a rare
      complication. A 40-year old male patient had been treated with azathioprine in
      consequence of extensive ulcerative colitis for 10 years. He then complained of 7
      d of fever, cough and catarrhal signs, without symptoms of active colitis.
      Opportunistic infections were ruled out. The chest X-ray, CT and lung biopsy
      demonstrated the presence of interstitial inflammation. Azathioprine therapy was
      discontinued as a potential source of the pulmonary infiltrate. In response to
      steroid therapy, and intensive care, the pulmonary infiltrate gradually decreased
      within 4 wk. Three months later, his ulcerative colitis relapsed, and ileo-anal
      pouch surgery was performed. In cases of atypical pneumonia, without a proven
      infection, azathioprine-associated interstitial pneumonitis may be present, which
      heals after withdrawal of the drug.

PMID- 17226918
TI  - Gallbladder lymphangioma: a case report and review of the literature.
AB  - Lymphangiomas are rare, benign tumors of the lymphatic system, usually present in
      children aged 5 years and younger. Because they are asymptomatic until the mass
      enlarges to cause symptoms, most lymphangiomas are diagnosed at adulthood
      incidentally. We experienced a case of a 60-year-old man diagnosed with a cystic
      lymphangioma of the gallbladder, which was successfully resected without any
      complication. Magnetic resonance imaging and magnetic resonance
      cholangiopancreatography were very helpful for the diagnosis of the cystic lesion
      around the gallbladder as were ultrasonography and computed tomography scan.
      These showed a multi-lobulated cystic mass with intact cystic duct and bile duct
      in the gallbladder fossa. The patient underwent an open cholecystectomy and the
      histological findings were consistent with a cystic lymphangioma of the
      gallbladder. We here report the case of cystic lymphangioma of the gallbladder
      with a review of the literature.

PMID- 17226920
TI  - Future of toxicology--lipid peroxidation in the future: from biomarker to
      etiology.
AB  - On the basis of a large number of reports concerning the detection of lipid
      peroxidation products as biomarkers in human diseases, there is no doubt that
      their steady-state levels increase under pathophysiological states associated
      with oxidative stress. The key question is whether they play any causative roles.
      This may be a matter of primary concern, which represents an important direction
      to pursue in the future of toxicology. My latest approach from autoimmune
      response induced by lipid peroxidation products will be illustrated.

PMID- 17226921
TI  - Conformation-specific recognition of carcinogen-DNA adduct in escherichia coli
      nucleotide excision repair.
AB  - We report a systematic and quantitative structure-function relationship study of
      the major N-[deoxyguanosin-8-yl]-2-aminofluorene adduct (AF) derived from the
      prototype carcinogen 2-aminofluorene and its derivatives. The AF adduct is known
      to exist in two distinct conformational motifs, depending upon the location of
      the hydrophobic fluorine moiety: major groove binding "B type" (B) conformation
      (AF-dGanti) and base-displaced "stacked" (S) conformation (AF-dGsyn). The AF
      induced S/B conformational heterogeneity is sequence-dependent and follows a
      typical two-site dynamic chemical exchange. The population of S conformation
      decreases in the order of 3'-G > A > C > T, indicating the importance of the
      purine flanking bases in promoting the stacking structure. Line-shape analysis
      showed that the S/B interconversion energy barriers (DeltaG) are in the narrow 14
      16 kcal/mol range. The energy differences of the two conformers are relatively
      small (<0.5 kcal/mol), suggesting a possibility for a facile adduct conformation
      switch in the active site of a polymerase. The S/B equilibrium modulates the
      efficiency of Escherichia coli UvrABC-based nucleotide excision repair (NER) in a
      conformation-specific manner. The 19F NMR/NER results indicate greater repair
      susceptibility for the base-displaced S conformer, which lacks a Watson-Crick
      base pair at the lesion site. These findings represent the first of its kind
      quantitative structure-function work relating NER activity to a specific adduct
      conformer and will lead to a better understanding of how bulky DNA adducts are
      accommodated by the repair protein.

PMID- 17226922
TI  - Structural determinants of binding of aromates to extracellular matrix: a multi
      species multi-mode CoMFA study.
AB  - For small molecules acting in tissues, including signaling peptides, effectors,
      inhibitors, and other drug candidates, nonspecific binding to the extracellular
      matrix (ECM) is a critical phenomenon affecting their disposition, toxicity, and
      other effects. A commercially available ECM mimic, forming a solidified layer at
      the bottom of the vials, was used to measure the association constants of 25
      simple aromatic compounds to two forms of ECM proteins, solidified (s-ECM) and
      dissolved (d-ECM) in the buffer during the incubation. Except for small
      homologous series, the binding data did not correlate with the lipophilicity and
      acidity of the compounds, contrary to a common expectation for nonspecific
      binding. To elucidate the putative structures of averaged binding sites of s-ECM
      and d-ECM, comparative molecular field analysis (CoMFA) was applied in a modified
      version taking into consideration that multiple modes and multiple species may be
      involved. The method shapes a receptor site model from a set of grid points in
      which the interaction energies between a probe atom and superimposed ligands are
      calculated. Electrostatic and steric energies in the grid points are
      characterized by regression coefficients. The forward-selection nonlinear
      regression analysis was used to optimize the coefficients in the novel multi
      species, multi-mode CoMFA models. These models showed satisfactory descriptive
      and predictive abilities for both s-ECM and d-ECM binding data, which were better
      than those obtained with the standard, one-mode CoMFA analysis. The calibrated
      models, defining the electrostatic and van der Waals regions of putative binding
      sites, are suitable for the prediction of ECM binding for untested chemicals.

PMID- 17226923
TI  - Lymphocyte loss and immunosuppression following acetaminophen-induced
      hepatotoxicity in mice as a potential mechanism of tolerance.
AB  - Current evidence suggests that drug-induced liver disease can be caused by an
      allergic response (drug-induced allergic hepatitis, DIAH) induced by hepatic drug
      protein adducts. The relatively low incidence of these reactions has led us to
      hypothesize that tolerogenic mechanisms prevent DIAH from occurring in most
      people. Here, we present evidence for the existence of one of these regulatory
      pathways. Following a hepatotoxic dose of acetaminophen in C57Bl/6 mice,
      lymphocyte loss that appeared to be due at least in part to apoptosis was noted
      in the spleen, thymus, and draining lymph nodes of the liver. There was no
      observable lymphocyte loss in the absence of hepatotoxicity. Acetaminophen
      induced liver injury (AILI) also led to a functional suppression of the immune
      system as determined by the inhibition of a delayed-type hypersensitivity
      response to dinitrochlorobenzene. Further studies with adrenalectomized mice
      suggested a role for corticosterone in the depletion of lymphocytes following
      APAP-induced liver injury. In conclusion, these findings suggest that lymphocyte
      loss and immunosuppression following AILI may prevent subsequent occurrences of
      allergic hepatitis and possibly other forms of APAP-induced allergies induced by
      hepatic drug-protein adducts. Similar regulatory pathways may inhibit other
      hepatotoxic drugs from causing allergic reactions.

PMID- 17226924
TI  - Binding of dimethylarsinous acid to cys-13alpha of rat hemoglobin is responsible
      for the retention of arsenic in rat blood.
AB  - The metabolism, disposition, and carcinogenicity of arsenic differ dramatically
      between humans and rats. To understand the molecular basis of these differences,
      we have characterized arsenic species in rats that were treated with inorganic
      arsenate (iAsV), monomethylarsonic acid (MMAV), or dimethylarsinic acid (DMAV)
      for up to 15 weeks. Arsenic significantly accumulated in the red blood cells
      (RBCs) of rats in the form of hemoglobin (Hb) complexed with dimethylarsinous
      acid (DMAIII), regardless of whether the rats were treated with iAsV, MMAV, or
      DMAV, suggesting rapid methylation of arsenic species followed by strong binding
      of DMAIII to rat Hb. The binding site for DMAIII was identified to be cysteine 13
      in the alpha-chain of rat Hb with a stoichiometry of 1:1. Over 99% of the total
      arsenic (maximum 2.5-3.5 mM) in rat RBCs was bound to Hb for all rats examined (n
      = 138). In contrast, only 40-49% of the total arsenic (maximum approximately 10
      muM) in rat plasma was bound to proteins. The ratios of the total arsenic in RBCs
      to that in plasma ranged from 88-423 for rats that were fed iAsV, 100-680 for
      rats that were fed MMAV, and 185-1393 for rats that were fed DMAV, when samples
      were obtained over the 15-week exposure duration. Previous studies have shown an
      increase in urothelial hyperplasia in rats fed DMAV. This is the first article
      reporting that treatment with iAsV in the drinking water also produces urothelial
      hyperplasia and at an even earlier time point than dietary DMAV. Dietary MMAV
      produced only a slight urothelial response. A correlation between the Hb-DMAIII
      complex and urothelial lesion severity in rats was observed. The lack of cysteine
      13alpha in human Hb may be responsible for the shorter retention of arsenic in
      human blood. These differences in the disposition of arsenicals may contribute to
      the observed differences between humans and rats in susceptibility to arsenic
      carcinogenicity.

PMID- 17226925
TI  - Lead-induced procoagulant activation of erythrocytes through phosphatidylserine
      exposure may lead to thrombotic diseases.
AB  - Lead (Pb) is a ubiquitous heavy metal pollutant in various environmental media,
      especially in food and drinking water. In human blood, about 95% of lead is
      associated with erythrocytes, suggesting that erythrocytes could be an important
      target of lead toxicity in the cardiovascular system. Recent studies suggested
      that erythrocytes could contribute to blood coagulation via phosphatidylserine
      (PS) exposure and resultant procoagulant activation. We investigated the effects
      of lead on the procoagulant activity of erythrocytes using in vitro human
      erythrocyte and in vivo rat models. In a flow cytometric analysis, lead (Pb2+)
      enhanced PS exposure on human erythrocytes in a concentration- and time-dependent
      manner. The concentration of lead (1-5 microM) used in the current investigation
      is well within the ranges observed in blood from lead-exposed populations. PS
      exposure by lead appeared to be mediated by increased intracellular calcium
      levels as shown by 19F-NMR and intracellular ATP depletion. Consistent with these
      findings, the activity of scramblase, which is important in the induction of PS
      exposure, was enhanced, whereas the activity of flippase, which translocates
      exposed PS to inner membrane, was inhibited by lead treatment. Furthermore, lead
      exposed erythrocytes increased thrombin generation as determined by a
      prothrombinase assay and accelerated the coagulation process initiated by tissue
      factor in plasma. These procoagulant activations by lead were also confirmed in
      vivo. Administration of lead significantly enhanced PS exposure on erythrocytes
      and, more importantly, elevated thrombus formation in a rat venous thrombosis
      model. These results suggest that lead exposure can provoke procoagulant activity
      in erythrocytes by PS exposure, contributing to enhanced clot formation. These
      data will provide new insights into the mechanism of lead-induced cardiovascular
      diseases.

PMID- 17226926
TI  - Electrophilic chemistry related to skin sensitization. Reaction mechanistic
      applicability domain classification for a published data set of 106 chemicals
      tested in the mouse local lymph node assay.
AB  - This article presents an overview of electrophilic reaction mechanisms relevant
      to skin sensitization, with reference to a published skin sensitization test data
      set for 106 chemicals. Where appropriate to aid the interpretation, additional
      data on a small number of further compounds are also discussed. It is shown that
      there is a close correspondence in the way differences and similarities in skin
      sensitization potency of chemicals relate to differences and similarities in
      their physical organic chemistry and electrophilic reaction mechanistic
      chemistry. The 106 chemicals are classified into their reaction mechanistic
      applicability domains, and reactivity-sensitization trends are analyzed for each
      domain: the Michael acceptor and pro-Michael acceptor electrophile domain; the
      SNAr electrophile domain; the SN2 electrophile domain; the Schiff base
      electrophile domain; the acyl transfer electrophile domain; and the non
      electrophilic non-pro-electrophilic domain. The last of these domains should be
      populated mainly by non-sensitizers. Classification of 87 of the 106 compounds,
      using these domains, was straightforward. In most of the domains and subdomains
      where there are sufficient compounds, clear trends can be seen, in conformity
      with the Relative Alkylation Index (RAI) model, between sensitization potential
      and reactivity/hydrophobicity. Of the remaining 19 compounds, 7 are alpha-X
      methyl-gamma-lactones that on the basis of published organic chemistry studies
      and guinea pig sensitization data can be classed as pro-Michael acceptors by
      elimination of HX but that are mostly negative in the LLNA, indicating a
      difference in bioactivation capabilities between mice and guinea pigs. The other
      12 compounds, whose chemistry was not immediately obvious, were found after
      further analysis and literature research to fit into appropriate mechanistic
      domains that rationalize their skin sensitizing properties.

PMID- 17226927
TI  - Electrophilic reactions of skin-sensitizing sultones.
AB  - Reactions of the strong skin sensitizer hexadec-1-ene-1,3-sultone with sodium
      hydroxide, sodium methoxide, sodium metabisulfite, sodium butanethiolate, n
      butylamine, and aniline have been investigated, and the reaction products have
      been identified. Most of the nucleophiles studied react by nucleophilic addition
      (Michael type addition) to the double bond at the 2-position, although in most
      cases the final products result from further reactions of the initital adducts.
      The findings are considered together with those reported by Meschkat, Barratt,
      and Lepoittevin for reactions of hex-1-ene-1,3-sultone and hexane-1,3-sultone,
      and the implications of the two sets of findings for the mechanism of skin
      sensitizing action are discussed. It is concluded that nucleophilic attack at the
      3-position of the alk-1-ene-1,3-sultones occurs only with those nucleophiles,
      which either have very low reactivity in nucleophilic addition or are unable to
      give rise to thermodynamically stable products via initial reaction at the 2
      position. It is further concluded that the observed differences in electrophilic
      reactivity between alk-1-ene-1,3-sultones and alkane-1,3-sultones are not large
      enough to rationalize the differences in skin sensitization properties between
      the two types of sultone. It is suggested that the differences in specificity
      arise because the alk-1-ene-1,3-sultones act as Michael type electrophiles
      whereas the alkane sultones act as SN2 electrophiles. It is suggested that the
      reason for the greater potency of the alk-1-ene-1,3-sultones may be the ability
      of the initial C2 adducts with protein to undergo further reactions by
      substitution at C3, leading to cross-linking and consequent perturbation to the
      protein tertiary structure.

PMID- 17226928
TI  - Cytotoxicity of a Quinone-containing Cockroach Sex Pheromone in Human Lung
      Adenocarcinoma Cells.
AB  - The cytotoxic effects of blattellaquinone (BTQ), a sex pheromone produced by
      adult female German cockroaches, have been studied using human lung
      adenocarcinoma A549 cells. 1,4-Benzoquinone (BQ), a toxic chemical implicated in
      benzene toxicity, was used as a reference compound. Both BQ and BTQ showed
      comparable toxicity toward A549 cells, with LD50 values estimated to be 14 and 19
      microM, respectively. These two compounds increased the formation of an oxidized
      fluorescent probe, 2',7'-dichlorofluorescein, but had no effect on the cellular
      GSSG level. Interestingly, BTQ increased the level of 8-epi-prostaglandin F2alpha
      and was 4-fold more efficient in depleting cellular GSH content than BQ. Of the
      five GSH adducts of BTQ isolated, three were identified as mono-GSH conjugates,
      and the other two were di-conjugates. Mass spectrometric and NMR analyses of the
      di-conjugates showed that the second GSH molecule displaced the isovaleric acid
      moiety, potentially via a nucleophilic substitution reaction. The ability of BTQ
      to conjugate a second GSH molecule without quinone regeneration indicated that it
      may be a more effective cross-linking agent than BQ. Future experiments may be
      needed to evaluate the overall safety of BTQ before the commercialization of the
      compound as a cockroach attractant.

PMID- 17226929
TI  - Kinetics and mechanism of the oxidation of the glutathione dimer by hypochlorous
      Acid and catalytic reduction of the chloroamine product by glutathione reductase.
AB  - Oxidized glutathione (GSSG) reacts with two molar equivalents of HOCl/OCl- (a
      neutrophil-derived oxidant and a common biocide) to form the dichloro (bis-N
      chloro-gamma-l-glutamyl) derivative (NDG). The reaction of less than two molar
      equivalents of HOCl with GSSG does not yield the unsymmetrical monochloro
      derivative (NCG) but rather a stoichiometric amount of NDG and GSSG. This result
      is explained by a faster reaction of the second equivalent of HOCl with NCG than
      that of the first equivalent of HOCl with GSSG. The rates of reaction of GSSG2-,
      GSSG3-, and GSSG4- (successive deprotonation of the ammonium groups) have been
      investigated, and it is clear that GSSG2- is unreactive, whereas GSSG4- is about
      twice as reactive as GSSG3-. Accordingly, the following mechanism is proposed
      (constants for 5 degrees C): H+ + OCl- = HOCl, pK1 = -7.47; GSSG2- = GSSG3- + H+,
      pK2 = 8.5; GSSG3- = GSSG4- + H+, pK3 = 9.5; GSSG3- + HOCl --> NCG3- + H2O, k4 =
      2.7(2) x 106 M-1 s-1; GSSG4- + HOCl --> NCG4- + H2O, k5 = 3.5(3) x 107 M-1 s-1;
      NCG3- --> NDG4- + H+, k6 = fast; and NCG4- + HOCl --> NDG4- + H2O, k7 = fast. At
      physiologic pH, the k4 pathway dominates. NDG decomposes at pH 7.4 in a first
      order process with kdec = 4.22(1) x 10-4 s-1 (t1/2 = 27 min). Glutathione
      reductase (EC 1.6.4.2) is capable of catalyzing the reduction of NDG by NADPH.
      The only NDG-derived product that is observed (by NMR) after the reduction by
      NADPH is GSH. Thus, in the presence of the GOR/NADPH system, GSH is capable of
      redox buffering a 3/2 mol equiv of HOCl rather than a 1/2 mol equiv as previously
      assumed.

PMID- 17226930
TI  - Hplc/electrospray ionization mass spectrometric analysis of the heterocyclic
      aromatic amine carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in
      human milk.
AB  - A new procedure has been developed for the extraction of 2-amino-1-methyl-6
      phenyl-imidazo[4,5-b]pyridine (PhIP) and other heterocyclic aromatic amines from
      human breast milk samples. Extracts were analyzed by high-performance liquid
      chromatography/electrospray ionization/tandem mass spectrometry (HPLC/ESI-MS/MS)
      with selective reaction monitoring detection. Tandem ESI-MS/MS detection provides
      much improved sensitivity and specificity, compared with those of a previous
      method that used selected ion monitoring. Milk samples were collected from 48
      healthy volunteers, including five vegetarians. Donors completed a detailed
      dietary questionnaire. The concentrations of PhIP in the milk samples were low
      and below the limit of quantification (0.68 pg/mL) for all subjects except one,
      for whom a concentration of 1.0 pg PhIP/mL was measured. Our results indicate
      that the levels of PhIP in human milk are substantially lower than what was
      previously reported.

PMID- 17226931
TI  - Desulfoyessotoxins from Adriatic mussels: a new problem for seafood safety
      control.
AB  - Two new desulfated yessotoxin (YTX) analogues were isolated from a toxic batch of
      Adriatic mussels collected in October 2004. Their stereostructures were
      elucidated through extensive NMR and MS-based analysis. The finding of these
      desulfocarboxyhomoYTXs in shellfish poses additional problems to those
      institutions entitled to control seafood safety, since desulfated YTXs fail the
      European Union method currently in force for checking toxicity in mollusks.

PMID- 17226932
TI  - Lipidomic analysis for lipid peroxidation-derived aldehydes using gas
      chromatography-mass spectrometry.
AB  - A lipidomic method is described for the measurement of lipid peroxidation-derived
      aldehydes using gas chromatography/electron ionization/mass spectrometry with
      selected ion monitoring (GC/EI/MS-SIM). Aldehydes in the samples were converted
      into their pentafluorobenzyl (PFB)-oximes using PFB-hydroxylamine, and other
      functional groups such as the hydroxyl groups were further derivatized into the
      trimethylsilyl ethers. The PFB-oxime derivatives could be comprehensively
      detected by the SIM of m/z 181, which is a characteristic fragment ion of the PFB
      oxime derivatives. At the same time, each aldehyde was classified into five
      groups (alkanals, 2-alkenals, 2,4-alkadienals, 2-hydroxyalkanals, and 4-hydroxy-2
      alkenals) by SIM of the structure-specific fragment ions. Determination of the 4
      hydroxy-2-alkenals was also performed by confirmation of their higher reactivity
      with the sulfhydryl group. On the basis of the mass spectrometric
      characterization, we have identified at least 33 aldehydes formed upon the FeII
      mediated decomposition of the arachidonic acid-, linoleic acid-, and
      docosahexaenoic acid-hydroperoxides in vitro. We then applied this system to the
      in vivo samples and successfully observed the increase in aldehydes in the liver
      of mice intraperitoneally injected with bromobenzene, an experimental animal
      model for lipid peroxidation. Using this comprehensive analysis, unique
      differences in the formation between each aldehyde could be observed. This method
      is useful for simultaneously monitoring the lipid peroxidation-derived aldehydes
      formed under oxidative stress in vivo.

PMID- 17226933
TI  - Quantitation of an acetaldehyde adduct in human leukocyte DNA and the effect of
      smoking cessation.
AB  - Acetaldehyde is one of the most prevalent carcinogens in cigarette smoke. It is
      also a major metabolite of ethanol and is found widely in the human diet and
      environment. Acetaldehyde DNA adducts are critical for its carcinogenic
      properties. The role of acetaldehyde DNA adducts in human cancer related to
      tobacco and alcohol exposure could be investigated with a suitable biomarker.
      Therefore, in this study, we have developed a method for analysis of the major
      DNA adduct of acetaldehyde, N2-ethylidene-dGuo (1), in human leukocyte DNA.
      Leukocyte DNA was subjected to enzyme hydrolysis in the presence of NaBH3CN,
      which converts adduct 1 to N2-ethyl-dGuo (2). [15N5]N2-ethyl-dGuo was used as the
      internal standard. After solid-phase extraction, N2-ethyl-dGuo was quantified by
      LC-ESI-MS/MS-SRM. The method was sensitive, accurate, and precise, and applicable
      to low microgram amounts of DNA. It was applied to investigate the effect of
      smoking cessation on levels of adduct 1, measured as adduct 2. Twenty-five
      smokers who were only light drinkers were eligible for the study. Levels of
      adduct 2 were quantified at two baseline time points separated by one week and
      again after four weeks of abstinence from smoking and alcohol consumption. The
      mean (+/-S.D.) levels of adduct 2 measured in the leukocytes of the smokers were
      1310 +/- 1720 (range 124-7700) and 1120 +/- 1140 (range 138-5760) fmol/micromol
      dGuo at the two baseline points and 705 +/- 438 (range 111-1530) fmol/micromol
      dGuo after 4 weeks of cessation. The median level of adduct 2 decreased
      significantly by 28% upon quitting smoking (P = 0.02). These results demonstrate
      that the major acetaldehyde DNA adduct can be reliably quantified by MS/MS
      methods in human leukocyte DNA and that cigarette smoking has a modest but
      significant effect on its levels.

PMID- 17226934
TI  - 4D-fingerprint categorical QSAR models for skin sensitization based on the
      classification of local lymph node assay measures.
AB  - Currently, the only validated methods to identify skin sensitization effects are
      in vivo models, such as the local lymph node assay (LLNA) and guinea pig studies.
      There is a tremendous need, in particular due to novel legislation, to develop
      animal alternatives, for eaxample, quantitative structure-activity relationship
      (QSAR) models. Here, QSAR models for skin sensitization using LLNA data have been
      constructed. The descriptors used to generate these models are derived from the
      4D-molecular similarity paradigm and are referred to as universal 4D
      fingerprints. A training set of 132 structurally diverse compounds and a test set
      of 15 structurally diverse compounds were used in this study. The statistical
      methodologies used to build the models are logistic regression (LR) and partial
      least-square coupled logistic regression (PLS-LR), which prove to be effective
      tools for studying skin sensitization measures expressed in the two categorical
      terms of sensitizer and non-sensitizer. QSAR models with low values of the Hosmer
      Lemeshow goodness-of-fit statistic, X(2)HL, are significant and predictive. For
      the training set, the cross-validated prediction accuracy of the logistic
      regression models ranges from 77.3% to 78.0%, whereas that of the PLS-logistic
      regression models ranges from 87.1% to 89.4%. For the test set, the prediction
      accuracy of logistic regression models ranges from 80.0% to 86.7%, whereas that
      of the PLS-logistic regression models ranges from 73.3% to 80.0%. The QSAR models
      are made up of 4D-fingerprints related to aromatic atoms, hydrogen bond
      acceptors, and negatively partially charged atoms.

PMID- 17226935
TI  - Chemical nature of stochastic generation of protein-based carbonyls: metal
      catalyzed oxidation versus modification by products of lipid oxidation.
AB  - An assessment of 2,4-dinitrophenylhydrazine (DNPH)-detectable protein-based
      carbonyls is one of the most common assays used to quantify oxidative stress in
      vitro and in vivo. In this study, we compared, for the lipid-binding protein beta
      lactoglobulin, the extent to which carbonyl reactivity could be introduced by
      adventitious metal-catalyzed oxidation (MCO) in the absence and presence of a
      polyunsaturated lipid or by treatment with various individual bifunctional lipid
      oxidation products capable of introducing carbonyls into proteins by adduction to
      nucleophilic side chains. With metal ions and either O2/reductant or H2O2 as the
      terminal oxidant, the maximal level of DNPH-detectable carbonyl generation
      obtainable in several hours was 0.1-0.2 mol carbonyl per mol protein monomer,
      with Cu(II) being more effective than Fe(II). Exposure instead to bifunctional
      lipoxidation-derived aldehydes (1-2 mM) generated in some cases in excess of 1
      mol carbonyl per mol protein. The rank order of carbonyl incorporation reactivity
      was acrolein > 4-oxo-2-nonenal > 4-hydroxy-2-nonenal > 2,4-decadienal >
      malondialdehyde. Protein cross-linking ability followed a somewhat different rank
      order. Parallel studies on reductively methylated beta-lactoglobulin revealed
      that His and Cys residues are intrinsically more responsible than Lys residues
      for carbonyl appearance and that the availability of Lys residues accounts for
      the reduction of carbonyl content at later time (presumably reflecting cross
      linking chemistry) that occurs for acrolein and 4-oxo-2-nonenal. Overall, these
      results suggest that DNPH reactivity observed physiologically on
      nonmetalloproteins may arise more from the attachment of lipid-derived products
      of oxidative stress than from adventitious MCO of side chains. Additional studies
      carried out to clarify the potential use of DNPH derivatization to tag peptide
      based carbonyls for mass spectrometric analysis revealed that DNPH derivatization
      can reverse under the conditions used for proteolysis.

PMID- 17226936
TI  - Metabolism and bioactivation of 3-methylindole by human liver microsomes.
AB  - Metabolism and bioactivation of 3-methylindole (3MI) were investigated in human
      liver microsomes. The metabolism of two deuterium-labeled analogues of 3MI
      permitted a relatively unambiguous identification of multiple metabolites and
      glutathione (GSH) adducts of reactive intermediates. A total of eight oxidized
      metabolites were detected, five of which were assigned as previously identified 3
      methyloxindole, 3-hydroxy-3-methylindolenine, 3-hydroxy-3-methyloxindole, 5
      hydroxy-3-methylindole, and 6-hydroxy-3-methylindole. Among the three new
      metabolites, one was either 4- or 7-OH-3-methylindole, and the other two were
      derived from additional oxidation on the phenyl ring of 3-methyloxindole. When
      GSH was added to the microsomal incubations, seven conjugates that had molecular
      ions corresponding to the incorporation of GSH and an atom of oxygen at m/z 453
      (group I) were produced, and two additional conjugates had molecular ions at m/z
      437 that corresponded to the incorporation of GSH with no additional oxygen
      (group II). Two conjugates in group I (m/z 453) were apparently derived by GSH
      addition to the 5,6-epoxide metabolite of 3-methyloxindole. These two GSH adducts
      were tentatively identified as 5-(glutathione-S-yl)-3-methyloxindole and 6
      (glutathione-S-yl)-3-methyloxindole. The most abundant conjugate in group I was
      identified as 3-(glutathione-S-yl)-3-methyloxindole, which substantiated the
      presence of the putative 2,3-epoxy-3-methylindole intermediate. The remaining
      four adducts in group I were likely formed by conjugation of GSH at different
      positions of the phenyl ring, possibly via oxidation of 5-hydroxy-3-methylindole
      and 6-hydroxy-3-methylindole to two very interesting new electrophilic
      benzoquinone imine intermediates. For the group II conjugates (m/z 437), two
      isomers were identified as 2-(glutathione-S-yl)-3-methylindole and 3-(glutathione
      S-yl-methyl)-indole. The former adduct was primarily derived from the 2,3-epoxide
      intermediate by thiol conjugation followed by dehydration. The latter adduct was
      consistent with our previously published work on the dehydrogenation of 3MI. In
      those studies, we showed that the reactive intermediate, 3-methylenenindolenine,
      was formed by hydrogen abstraction at the methyl group and was trapped with GSH.
      The putative dehydrogenation bioactivation mechanism is also substantiated by the
      finding that CYP2E1 selectively generated 2-(glutathione-S-yl)-3-methylindole but
      did not produce 3-(glutathione-S-yl-methyl)-indole. In summary, the results not
      only confirmed the formation of 2,3-epoxide-3-methylindole in human liver
      microsomes but also suggested that the phenolic metabolites of 3-methylindole
      were dehydrogenated to previously uncharacterized reactive intermediates.

PMID- 17226937
TI  - Glutathione transferase omega 1 catalyzes the reduction of S
      (phenacyl)glutathiones to acetophenones.
AB  - S-(Phenacyl)glutathione reductase (SPG-R) plays a significant role in the
      biotransformation of reactive alpha-haloketones to nontoxic acetophenones.
      Comparison of the apparent subunit size, amino acid composition, and catalysis of
      the reduction of S-(phenacyl)glutathiones indicated that a previously described
      rat SPG-R (Kitada, M., McLenithan, J. C., and Anders, M. W. (1985) J. Biol. Chem.
      260, 11749-11754) is homologous to the omega-class glutathione transferase GSTO1
      1. The available data show that the SPG-R reaction is catalyzed by GSTO1-1 and
      not by other GSTs, including the closely related GSTO2-2 isoenzyme. In the
      proposed reaction mechanism, the active-site cysteine residue of GSTO1-1 reacts
      with the S-(phenacyl)glutathione substrate to give an acetophenone and a mixed
      disulfide with the active-site cysteine; a second thiol substrate (e.g.,
      glutathione or 2-mercaptoethanol) reacts with the active-site disulfide to
      regenerate the catalytically active enzyme and to form a mixed disulfide. A new
      spectrophotometric assay was developed that allows the rapid determination of SPG
      R activity and specific measurement of GSTO1-1 in the presence of other GSTs.
      This is the first specific reaction attributed to GSTO1-1, and these results
      demonstrate the catalytic diversity of GSTO1-1, which, in addition to SPG-R
      activity, catalyzes the reduction of dehydroascorbate and monomethylarsonate(V)
      and also possesses thioltransferase and GST activity.

PMID- 17226938
TI  - Effect of alterations of key active site residues in O6-alkylguanine-DNA
      Alkyltransferase on its ability to modulate the genotoxicity of 1,2
      dibromoethane.
AB  - The production of mutations and the reduction in survival of cells treated with
      alpha,omega-dihaloalkanes is greatly enhanced by the presence of O6-alkylguanine
      DNA alkyltransferase (AGT), a DNA repair protein that removes O6-alkylguanine
      adducts from DNA [Liu, L., Hachey, D. L., Valadez, G., Williams, K. M.,
      Guengerich, F. P., Loktionova, N. A., Kanugula, S., and Pegg, A. E. (2004) J.
      Biol. Chem. 279, 4250-4259]. The effects of alterations to key residues in the
      active site of AGT were studied using AGTs with point mutations. It was found
      that mutants of AGT at positions Tyr114, Arg128, Pro140, Gly156, Gly160, and
      Tyr158 did not bring about the increase in genotoxicity of 1,2-dibromoethane seen
      with wild-type AGT, although these mutants, with the exception of those at Tyr114
      and Arg128, are known to have sufficient AGT repair function to be able to
      protect cells from alkylating agents. The R128A mutant was able to react with 1,2
      dibromoethane at the Cys145 acceptor site, but the resulting AGT-Cys145S-(CH2)2Br
      was much less able to produce a covalent adduct with DNA. This result is
      explained by the need for AGT to induce a structural change in the DNA "flipping"
      of a guanine nucleotide into the substrate binding pocket where Cys145 is located
      since the side chain of residue Arg128 plays a critical role in this reaction.
      Point mutations in AGT at the other sites (Y114A, P140K, and Y158H) reduced the
      ability of the protein to react with 1,2-dibromoethane as measured by the loss of
      activity. These results were confirmed by MS analysis of the tryptic peptide that
      contains the modified Cys145. There was no change in the stability of the AGT
      Cys145S-(CH2)2Br intermediate formed in mutants Y158H and P140K. The reaction was
      studied in detail with mutant P140K using dihaloalkanes of different length; no
      effect of the mutations was seen with dibromomethane, but an enhanced difference
      was observed with 1,3-dibromopropane and 1,5-dibromopentane. These results show
      that even slight alterations in the active site pocket of AGT that do not prevent
      its ability to protect cells from alkylating agents can block the paradoxical
      enhancement of the genotoxicity of the larger alpha,omega-dihaloalkanes by
      reducing the reaction with Cys145.

PMID- 17226940
TI  - Dynamic processes leading to covalent bond formation for S(N)1 reactions.
AB  - The SN1 reaction mechanism is one of the most fundamental processes in organic
      chemistry. As such, it has been the subject of study for over 70 years with the
      purpose of seeking to understand the fundamental parameters that control
      reactivity. With recent advances in both electronic structure theory and condense
      phase reaction dynamics theory as well as in experimental probes of these
      reactions on the femtosecond and picosecond time scale, we are beginning to gain
      new insights into the nature of these reactions.

PMID- 17226941
TI  - Polar order by rational design: crystal engineering with parallel beloamphiphile
      monolayers.
AB  - Polar order in the biosphere is limited to nanometer-sized domains, occurs with
      essentially complete cancellation, or is avoided on purpose. One thus wonders
      whether large-scale polar order is even possible, and this question is the
      subject of the dipole alignment problem. We addressed this challenge with an
      interdisciplinary approach bringing together elements of mathematics, electronic
      structure theory and computational chemistry, physical-organic and synthetic
      chemistry, crystallization and crystallography, and, most importantly, patience
      and much thought about intermolecular bonding in molecular crystals. The azine-
      and biphenyl-based beloamphiphiles (Y-Ph-MeC=N-N=CMe-Ph-X and Y-Ph-Ph-X) are
      ascendants of a new generation of highly anisotropic functional materials with
      perfect polar order.

PMID- 17226942
TI  - Studies of electronic coupling and mixed valency in metal-metal quadruply bonded
      complexes linked by dicarboxylate and closely related ligands.
AB  - Complexes of the form [(tBuCO2)3M2]2(mu-O2C-X-CO2), where M is Mo or W and X is a
      pi conjugated organic group, are ideally suited for studies of electronic
      coupling between the two redox centers via M2 delta-bridge pi conjugation. The
      complexes have intense metal-to-bridge charge-transfer transitions in the visible
      or near-IR region of the spectrum and exhibit thermo-, solvato- and
      electrochromic behavior. Chemical oxidation results in the formation of mixed
      valence species that are particularly well-suited for the study of the class
      II/III border. The extent of electronic coupling is determined by a variety of
      spectroscopic techniques and, in particular, by EPR and electronic absorption
      spectroscopy. The latter provides a direct measure of the electronic coupling
      parameter Hab in pairs (Mo and W) of otherwise identical complexes. Similarly,
      the substitution within the bridge of the CO2 group by COS or RNCO allows an
      evaluation of the mechanism of the electronic coupling in closely related
      complexes. Electronic structure calculations employing density functional theory
      complement frontier molecular orbital theory in the interpretation of the
      physicochemical properties of these complexes.

PMID- 17226943
TI  - Organization of zeolite microcrystals for production of functional materials.
AB  - This Account summarizes various methods of organizing zeolite microcrystals into
      two-dimensional functional entities such as monolayers, multilayers, and
      patterned monolayers on various substrates and three-dimensional functional
      entities such as microballs and protein-zeolite composite fibrils. In the case of
      monolayer assembly, various types of linkages and substrates, factors that govern
      the rate, degree of coverage, degree of close packing, degree of uniform
      orientation, and average binding strength between each crystal and the substrate
      are described. The current and future applications of the organized products are
      also discussed.

PMID- 17226944
TI  - Metal-based turn-on fluorescent probes for sensing nitric oxide.
AB  - Nitric oxide, a reactive free radical, regulates a variety of biological
      processes. The absence of tools to detect NO directly, rapidly, specifically, and
      selectively motivated us to synthesize metal-based fluorescent probes to
      visualize the presence of NO. We prepared and investigated Co(II), Fe(II),
      Ru(II), Rh(II), and Cu(II) complexes as turn-on fluorescent NO sensors. Our
      exploration has provided insight into how the interaction of transition-metal
      centers with nitric oxide can be utilized for NO sensing.

PMID- 17226945
TI  - Plasmonic nanostructures: artificial molecules.
AB  - This Account describes a new paradigm for the relationship between the geometry
      of metallic nanostructures and their optical properties. While the interaction of
      light with metallic nanoparticles is determined by their collective electronic or
      plasmon response, a compelling analogy exists between plasmon resonances of
      metallic nanoparticles and wave functions of simple atoms and molecules. Based on
      this insight, an entire family of plasmonic nanostructures, artificial molecules,
      has been developed whose optical properties can be understood within this
      picture: nanoparticles (nanoshells, nanoeggs, nanomatryushkas, nanorice), multi
      nanoparticle assemblies (dimers, trimers, quadrumers), and a nanoparticle-over
      metallic film, an electromagnetic analog of the spinless Anderson model.

PMID- 17226946
TI  - Modular and dynamic functionalization of polymeric scaffolds.
AB  - The design and synthesis of multifunctionalized, architecturally controlled
      polymers is a prerequisite for a variety of future applications of polymeric
      materials. On the basis of Nature's use of self-assembly in the creation of
      biomaterials, this Account describes concepts that were developed over the past 5
      years that utilize noncovalent interactions such as hydrogen bonding, ionic
      interactions, electrostatic interactions, metal coordination, and pi-pi stacking
      in modification of copolymer side-chains to obtain multifunctional polymeric
      materials, induce polymer morphology changes, and influence bulk-polymer
      properties.

PMID- 17226947
TI  - Ultrafast 2D IR vibrational echo spectroscopy.
AB  - The experimental technique and applications of ultrafast two-dimensional infrared
      (2D IR) vibrational echo spectroscopy are presented. Using ultrashort infrared
      pulses and optical heterodyne detection to provide phase information, unique
      information can be obtained about the dynamics, interactions, and structures of
      molecular systems. The form and time evolution of the 2D IR spectrum permits
      examination of processes that cannot be studied with linear infrared absorption
      experiments. Three examples are given: organic solute-solvent complex chemical
      exchange, dynamics of the hydrogen-bond network of water, and assigning peaks in
      an IR spectrum of a mixture of species.

PMID- 17226948
TI  - Effect of carboxylate-binding mode on metal binding/selectivity and function in
      proteins.
AB  - We delineate the factors governing the carboxylate-binding mode (monodentate vs
      bidentate) in metalloproteins. We reveal how the carboxylate-binding mode affects
      the binding affinity and selectivity of a metal ion as well as the function of a
      metalloprotein using Ca2+-binding proteins and enzymes (ribonuclease H1,
      phosphoserine phosphatase, and ribonucleotide reductase) as examples. The
      collected data indicate that a carboxylate monodentate left arrow over right
      arrow bidentate switch, in addition to other structural factors, could be used to
      fine tune the metal-binding site affinity and/or selectivity, thus modifying the
      function/properties of the metalloprotein.

PMID- 17226951
TI  - Polyketal microparticles: a new delivery vehicle for superoxide dismutase.
AB  - There is currently great interest in developing microparticles that can enhance
      the delivery of proteins to macrophages. In this communication, we present a new
      acid-sensitive polymer for drug delivery, poly(cyclohexane-1,4-diyl acetone
      dimethylene ketal) (PCADK). PCADK is designed to hydrolyze, after phagocytosis by
      macrophages, in the acidic environment of the phagosome and enhance the
      intracellular delivery of phagocytosed therapeutics. Other key attributes of
      PCADK for drug delivery are its well-characterized degradation products and
      straightforward synthesis. PCADK hydrolyzes into 1,4-cyclohexanedimethanol, a
      compound used in food packaging, and acetone, a compound on the FDA GRAS list.
      PCADK was synthesized using the acetal exchange reaction between 1,4
      cyclohexanedimethanol and 2,2-dimethoxypropane, and could be obtained on a
      multigram scale in one step. The hydrolysis kinetics of the ketal linkages in
      PCADK were measured by 1H NMR and were determined to be pH-sensitive, having a
      half-life of 24.1 days at pH 4.5 and over 4 years at pH 7.4. The therapeutic
      enzyme superoxide dismutase (SOD), which scavenges reactive oxygen species, was
      encapsulated into PCADK-based microparticles using a double emulsion procedure.
      Cell culture experiments demonstrated that PCADK-based microparticles
      dramatically improved the ability of SOD to scavenge reactive oxygen species
      produced by macrophages. We anticipate numerous applications of PCADK in drug
      delivery, based on its acid sensitivity, well-characterized degradation products,
      and straightforward synthesis.

PMID- 17226952
TI  - N-(Iodoacetyl)-N'-(anthraquinon-2-oyl)-ethylenediamine (IAED): a new
      heterobifunctional reagent for the preparation of biochips.
AB  - Design and synthesis of a new heterobifunctional reagent, N-(iodoacetyl)-N'
      (anthraquinon-2-oyl)-ethylenediamine (IAED), have been described for the
      preparation of oligonucleotide-based biochips. The performance of the featured
      reagent is probed by the immobilization of thiolated and thiophosphorylated
      oligonucleotides on modified glass microslides via two routes (routes A and B).
      The immobilization procedure was accelerated by performing a chemical reaction
      between thiolated oligomers and the iodoacetyl moiety of the reagent under
      microwaves (MW), where it is completed in just 10 min. The quality of the
      constructed oligonucleotide microarrays was tested by performing a hybridization
      assay with a complementary target and subsequently used for the detection of base
      mismatches. The immobilized probes were found to be thermally stable.

PMID- 17226953
TI  - Visualization of the degradation of a disulfide polymer, linear poly(ethylenimine
      sulfide), for gene delivery.
AB  - Polyethylenimine (PEI) shows high transfection efficiency and cytoxicity due to
      its high amine density. The new disulfide cationic polymer, linear
      poly(ethylenimine sulfide) (l-PEIS), was synthesized for efficient and safe gene
      delivery. As the amine density of l-PEIS increased, the transfection efficiency
      also increased. l-PEIS-6 and l-PEIS-8 show transfection efficiencies that are
      similar to that of PEI. However, cytotoxicity of l-PEIS was not observed due to
      the biodegradable disulfide bond. The disulfide bonds are stable in the oxidative
      extracellular condition and can be degraded rapidly in the reductive
      intracellular condition. The degradation of l-PEIS in HeLa cells was visualized
      by fluorescence microscopy using the probe-probe dequenching effect of BODIPY-FL
      fluorescence dye. l-PEIS was degraded completely within 3 h.

PMID- 17226954
TI  - Poly(glycoamidoamine)s for gene delivery. structural effects on cellular
      internalization, buffering capacity, and gene expression.
AB  - The study of polymeric nucleic acid delivery vehicles has recently grown because
      of their promise for many biomedical applications. In an effort to understand how
      the chemical traits of polymers affect the biological mechanisms of nucleic acid
      delivery, we have calculated the buffering capacity in the physiological pH range
      of a series of 10 poly(glycoamidoamine)s with systematic structural variations in
      the amine stoichiometry (from 1 to 4), carbohydrate moiety (d-glucarate or l
      tartarate), and amine spacer (ethylene or butylene) within their repeat units. In
      addition, we have compared the buffering capacity of these polymeric vectors to
      their polyplex (polymer-DNA complex) stability, cellular internalization, and
      gene expression profiles to understand the parameters that are important for
      increasing gene delivery efficiency. The results indicate that the buffering
      capacity is not always the primary characteristic that determines the gene
      delivery efficiency for all the poly(glycoamidoamine)s. We have found that the
      buffering capacity may affect the gene delivery efficiency only when analogous
      structures containing the same number of amines but different carbohydrates are
      compared. We reveal that the cellular internalization is the key step in the gene
      delivery process with systems containing different amine stoichiometry. Also,
      increasing the number of methylene groups between the secondary amines increases
      toxicity to a large degree. This systematic and heuristic approach of studying
      the correlations between structural variables and gene delivery efficiency will
      facilitate the development of effective synthetic vectors for specific nucleic
      acid delivery applications.

PMID- 17226955
TI  - Tat-functionalized near-infrared emissive polymersomes for dendritic cell
      labeling.
AB  - Dendritic cells (DCs) play a pivotal role in both immune tolerance and the
      initiation of immunological responses. The ability to track DCs in vivo is
      imperative for the development of DC-based cellular therapies and to advance our
      understanding of DC function and pathophysiology. Here, we conjugate a cell
      permeable peptide, Tat, to near-infrared (NIR) emissive polymersomes in order to
      enable efficient intracellular delivery for future DC tracking with these optical
      probes. NIR imaging allows quantitative, repetitive, in vivo detection of
      fluorophore-laden cells, at centimeter tissue depths without disturbing cellular
      function. Flow cytometry and confocal microscopy results indicate that Tat
      mediated polymersome delivery to DCs is concentration and time dependent,
      resulting in punctate intracellular localization. Further, loading cells with Tat
      NIR emissive polymersomes does not interfere with cytokine-induced DC maturation
      and has modest effects on DC viability, but has a significant effect on mature DC
      induced activation of naive T cells. We observe significant uptake of NIR
      emissive polymersomes when conjugated to the peptide, with a lower detection
      limit of 5000 labeled DCs. The extent of polymersome delivery is estimated as 70
      000 +/- 10 000 vesicles/cell, equivalent to 0.7 +/- 0.1 fmol of NIR fluorophore.
      Our studies will enable future in vivo tracking of ex vivo labeled DCs by NIR
      fluorescence based imaging.

PMID- 17226956
TI  - Tumor cell targeting of transferrin-PEG-TNF-alpha conjugate via a receptor
      mediated delivery system: design, synthesis, and biological evaluation.
AB  - PEGylation is a procedure of growing interest for enhancing the therapeutic and
      biotechnological potential of peptides and proteins. Transferrin (Tf) has been
      proposed to be useful for targeting cancer cells. The aim of this study was to
      modify PEGylated recombinant human tumor necrosis factor alpha (PEG-TNF-alpha)
      with Tf to form Tf-PEG-TNF-alpha conjugates, which would maintain the advantages
      of PEGylation and also achieve the function of active targeting to tumor cells.
      In PEGylation reactions with 5-, 20-, 40-, and 60-fold molar excess of 3.4 kDa N
      hydroxysuccinimide-PEG-maleimide (PT1, PT2, PT3, and PT4, respectively), PEG-TNF
      alpha conjugates with different PEG chains were synthesized. A perfusion
      chromatography technique using a cation-exchange column was introduced to purify
      PEG-TNF-alpha conjugates. PT4 with about five PEG chains was selected as a lead
      candidate due to highest extent of PEGylation and maximum reaction yield.
      Thiolated Tf was conjugated to the maleimide group at the distal end of the PEG
      chains on the PEG-TNF-alpha conjugates, with the resulting Tf-PEG-TNF-alpha
      conjugates after purification containing approximately one Tf ligand on one TNF
      alpha molecule. The conjugate of Tf and PT4 (TPT4) was selected to assess the
      specificity and affinity to transferrin receptor (TfR) on two kinds of tumor
      cells, K562 and KB. Both the receptor binding assays and the competition
      experiments were performed using radioligand binding analysis. The results
      demonstrated that TPT4 as well as Tf bound specifically to the TfR on the tumor
      cell surface and the affinity of the conjugate to TfR was similar to that of
      native Tf. In contrast, PEG-TNF-alpha demonstrated no specificity. The
      biodistribution and antitumor effects were investigated in S-180 tumor-bearing
      mice. It was found that TPT4 could markedly alter in vivo behavioral
      characteristics of TNF-alpha. Compared with TNF-alpha and PT4, extravasated TPT4
      in tumor tissues exhibited a significantly delayed blood clearance and the
      highest intratumoral TNF-alpha levels. Furthermore, the inhibitory rate of tumor
      of TPT4 enhanced 5.3- and 1.8-fold over that of TNF-alpha and PT4, indicating
      that TPT4 exhibited the highest antitumor activity. These results suggested that
      Tf-PEG-TNF-alpha was a useful long circulating conjugate with the capabilities of
      specific receptor binding resulting in enhanced antitumor activity of TNF-alpha.

PMID- 17226957
TI  - Stability of cell-penetrating peptide-morpholino oligomer conjugates in human
      serum and in cells.
AB  - Cell penetrating peptides (CPPs) have been shown to enhance the cellular uptake
      of antisense oligonucleotides (AOs). However, the effectiveness of the CPPs for
      cytoplasmic or nuclear delivery of therapeutic AOs must take into account the
      possible entrapment of the CPP-AO conjugates in endosomes/lysosomes and the
      overall stability of the CPP-AO conjugates to enzymes. This includes the
      stabilities of the CPPs and AOs themselves as well as the linkage between them.
      In this study, we investigated the effects of several structural features of
      arginine-rich CPPs on the metabolic stability of CPP conjugated to
      phosphorodiamidate morpholino oligomers (PMOs) in human serum and in cells. Those
      structural features include amino acid configurations (d or l), incorporation of
      non-alpha-amino acids, peptide sequences, and types of linkages between CPPs and
      PMOs. Using matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry, we found that the stability of the CPP portion was varied although
      the PMO portion of the conjugate was completely stable both in cells and in human
      serum. d-Configuration CPPs were completely stable, while l-CPPs were degraded in
      both serum and HeLa cells. Insertions of 6-aminohexanoic acid residues (X) into
      an R8 peptide increased the corresponding CPP's serum stability with the degree
      of stability being dependent upon the positions of X. However, X-containing CPPs
      were degraded rapidly intracellularly. Insertions of beta-alanines (B) into the
      R8 peptide increased its serum stability and intracellular stability. An amide or
      a maleimide linkage was stable in both serum and cells; however, an unhindered
      disulfide linkage was not stable in either. By using fluorescent microscopy, flow
      cytometry, and an antisense splice correction assay, the cellular uptakes of an X
      containing conjugate and its fragments were compared to their antisense
      activities. We found that a large fraction of the conjugate was trapped within
      vesicles and the degraded fragments cannot escape from the vesicles. This study
      indicates that the incorporation of non-alpha-amino acids into l-CPPs can
      increase the metabolic stability of CPP-PMOs without using costly d-CPPs.
      However, the position and type of non-alpha-amino acids affect the degree of
      stability extracellularly and intracellularly. In addition, this study reveals
      that the degradation of an X-containing CPP-PMO conjugate is a more rapid process
      than degradation of a B-containing conjugate. Last, the endosomal/lysosomal
      trapping limits the effectiveness of a CPP-PMO conjugate, and the stability of
      the CPP is one of the factors affecting the ability of the conjugate to escape
      the endosomes/lysosomes.

PMID- 17226958
TI  - Site-specific PEGylation of protein disulfide bonds using a three-carbon bridge.
AB  - The covalent conjugation of a functionalized poly(ethylene glycol) (PEG) to
      multiple nucleophilic amine residues results in a heterogeneous mixture of PEG
      positional isomers. Their physicochemical, biological, and pharmaceutical
      properties vary with the site of conjugation of PEG. Yields are low because of
      inefficient conjugation chemistry and production costs high because of complex
      purification procedures. Our solution to these fundamental problems in PEGylating
      proteins has been to exploit the latent conjugation selectivity of the two sulfur
      atoms that are derived from the ubiquitous disulfide bonds of proteins. This
      approach to PEGylation involves two steps: (1) disulfide reduction to release the
      two cysteine thiols and (2) re-forming the disulfide by bis-alkylation via a
      three-carbon bridge to which PEG was covalently attached. During this process,
      irreversible denaturation of the protein did not occur. Mechanistically, the
      conjugation is conducted by a sequential, interactive bis-alkylation using
      alpha,beta-unsaturated beta'-monosulfone functionalized PEG reagents. The
      combination of (a) maintaining the protein's tertiary structure after disulfide
      reduction, (b) the mechanism for bis-thiol selectivity of the PEG reagent, and
      (c) the steric shielding of PEG ensure that only one PEG molecule is conjugated
      at each disulfide bond. PEG was site-specifically conjugated via a three-carbon
      bridge to 2 equiv of the tripeptide glutathione, the cyclic peptide hormone
      somatostatin, the tetrameric protein l-asparaginase, and to the disulfides in
      interferon alpha-2b (IFN). SDS-PAGE, mass spectral, and NMR analyses were used to
      confirm conjugation, thiol selectivity, and connectivity. The biological activity
      of the l-asparaginase did not change after the attachment of four PEG molecules.
      In the case of IFN, a small reduction in biological activity was seen with the
      single-bridged IFN (without PEG attached). A significantly larger reduction in
      biological activity was seen with the three-carbon disulfide single-bridged PEG
      IFNs and with the double-bridged IFN (without PEG attached). The reduction of the
      PEG-IFN's in vitro biological activity was a consequence of the steric shielding
      caused by PEG, and it was comparable to that seen with all other forms of PEG
      IFNs reported. However, when a three-carbon bridge was used to attach PEG, our
      PEG-IFN's biological activity was found to be independent of the length of the
      PEG. This property has not previously been described for PEG-IFNs. Our studies
      therefore suggest that peptides, proteins, enzymes, and antibody fragments can be
      site-specifically PEGylated across a native disulfide bond using three-carbon
      bridges without destroying their tertiary structure or abolishing their
      biological activity. The stoichiometric efficiency of this approach also enables
      recycling of any unreacted protein. It therefore offers the potential to make
      PEGylated biopharmaceuticals as cost-effective medicines for global use.

PMID- 17226960
TI  - Influence of different spacers on the biological profile of a DOTA-somatostatin
      analogue.
AB  - Radiolabeled somatostatin analogues have been successfully used for targeted
      radiotherapy and for imaging of somatostatin receptor (sst1-5)-positive tumors.
      Nevertheless, these analogues are subject to improving their tumor-to-nontarget
      ratio to enhance their diagnostic or therapeutic properties, preventing
      nephrotoxicity. In order to understand the influence of lipophilicity and charge
      on the pharmacokinetic profile of [1,4,7,10-tetraazacyclododecane-1,4,7,10
      tetraacetic acid (DOTA)]-somatostatin-based radioligands such as [DOTA,1-Nal3]
      octreotide (DOTA-NOC), different spacers (X) based on 8-amino-3,6-dioxaoctanoic
      acid (PEG2), 15-amino-4,7,10,13-tetraoxapentadecanoic acid (PEG4), N-acetyl
      glucosamine (GlcNAc), triglycine, beta-alanine, aspartic acid, and lysine were
      introduced between the chelator DOTA and the peptide NOC. All DOTA-X-NOC
      conjugates were synthesized by Fmoc solid-phase synthesis. The partition
      coefficient (log D) at pH = 7.4 indicated that higher hydrophilicity than [111In
      DOTA]-NOC was achieved with the introduction of the mentioned spacers, except
      with triglycine and beta-alanine. The high affinity of [InIII-DOTA]-NOC for human
      sst2 (hsst2) was preserved with the structural modifications, while an overall
      drop for hsst3 affinity was observed, except in the case of [InIII-DOTA]-beta-Ala
      NOC. The new conjugates preserved the good affinity for hsst5, except for [InIII
      DOTA]-Asn(GlcNAc)-NOC, which showed decreased affinity. A significant 1.2-fold
      improvement in the specific internalization rate in AR4-2J rat pancreatic tumor
      cells (sst2 receptor expression) at 4 h was achieved with the introduction of Asp
      as a spacer in the parent compound. In sst3-expressing HEK cells, the specific
      internalization rate at 4 h for [111In-DOTA]-NOC (13.1% +/- 0.3%) was maintained
      with [111In-DOTA]-beta-Ala-NOC (14.0% +/- 1.8%), but the remaining derivatives
      showed <2% specific internalization. Biodistribution studies were performed with
      Lewis rats bearing the AR4-2J rat pancreatic tumor. In comparison to [111In-DOTA]
      NOC (2.96% +/- 0.48% IA/g), the specific uptake in the tumor at 4 h p.i. was
      significantly improved for the 111In-labeled sugar analogue (4.17% +/- 0.46%
      IA/g), which among all the new derivatives presented the best tumor-to-kidney
      ratio (1.9).

PMID- 17226959
TI  - Incorporation of CpG oligonucleotide ligand into protein-loaded particle vaccines
      promotes antigen-specific CD8 T-cell immunity.
AB  - The development of multicomponent biotherapeutic carriers is an important
      challenge in the field of drug delivery, particularly in the area of protein
      based vaccines. While the delivery of protein antigens to antigen presenting
      cells (APCs) is crucial for this type of vaccination, the incorporation of
      additional adjuvants may be just as important in order to generate more potent
      immune responses. This article presents the synthesis and biological evaluation
      of carrier particles that both deliver a protein payload to APCs and display
      receptor ligands for the enhancement of APC immunostimulation. Particles
      displaying CpG oligonucleotide ligands for Toll-like receptor 9 were synthesized.
      The addition of CpG DNA to the particles led to a 45-fold increase in the
      secretion of interleukin-12, a cytokine that aids in T-cell activation, and a
      significant increase in the expression of costimulatory molecules by APCs.
      Moreover, vaccination with particles containing both ovalbumin (OVA) and CpG DNA
      induced a superior OVA-specific CD8 T-cell response in vivo, as measured by
      increased OVA-specific CD8 T-cell proliferation, secretion of the proinflammatory
      cytokine IFN-gamma, and the induction of OVA-specific cytotoxicity.

PMID- 17226961
TI  - Synthesis, DNA interaction, and cytotoxic activity of a novel proflavine
      dithiazolidinone pharmacophore.
AB  - Five novel proflavine-dithiazolidinone derivatives 4a-4e have been designed and
      synthesized by the reaction of dialkyl acridin-3,6-diyl dithioureas 3a-3e with
      methyl bromoacetate. The binding affinity of dithiazolidinone hydrochlorides 5a
      5e with calf thymus DNA and plasmid (pUC19) DNA was investigated by a variety of
      spectroscopic techniques including UV-vis, fluorescence, and CD spectroscopy. The
      effects of 5a-5e on the thermal denaturation profiles of calf thymus DNA were
      also studied. From spectrophotometric and spectrofluorimetric titrations, the
      binding constants for the pUC19 DNA-drug complexes were determined (K = 6.2-2.2 x
      104 M-1). In vitro cytotoxic activities of compounds 5a-5e toward murine leukemia
      cell line L1210 and human uterus carcinoma HeLa cells were also examined. 2',2' '
      [(Acridin-3,6-diyl)diimino]-3',3' '-dipropyl-1,3-dithiazolidin-4-one
      hydrochloride (5b) showed the highest activity against these cells with IC50
      values of 6.3 microM and 12.9 microM over the course of 72 h.

PMID- 17226962
TI  - Synthesis of cetuximab-immunoliposomes via a cholesterol-based membrane anchor
      for targeting of EGFR.
AB  - The objective of the present study was to construct epidermal growth factor
      receptor (EGFR) targeting cetuximab-immunoliposomes (ILs) for targeted delivery
      of boron compounds to EGFR(+) glioma cells for neutron capture therapy. The ILs
      were synthesized by using a novel cholesterol-based membrane anchor, maleimido
      PEG-cholesterol (Mal-PEG-Chol), to incorporate cetuximab into liposomes by either
      surface conjugation or a post-insertion method. For post-insertion, the transfer
      efficiency of MAb conjugates from micelles to liposome was examined at varying
      temperatures, mPEG2000-DSPE ratios, and micelle-to-liposome lipid ratios.
      Following this, the cetuximab-ILs were evaluated for targeted delivery of the
      encapsulated boron anion, dodecahydro-closo-dodecaborate (2-) (B12H122-), to
      human EGFR gene transfected F98EGFR glioma cells as potential delivery agents for
      boron neutron capture therapy (BNCT). In addition, cellular uptake of cetuximab
      ILs, encapsulating a fluorescence dye, was analyzed by confocal fluorescence
      microscopy and flow cytometry, and boron content was quantified by ICP-MS. Much
      greater ( approximately 8-fold) cellular uptake of boron was obtained using
      cetuximab-ILs in EGFR(+) F98EGFR compared with nontargeted human IgG-ILs. On the
      basis of these observations, we have concluded that cholesterol can serve as an
      effective anchor for MAb in liposomes, and cetuximab-ILs are potentially useful
      delivery vehicles for BNCT of gliomas.

PMID- 17226963
TI  - Enzymatic and nonenzymatic synthesis of glutathione conjugates: application to
      the understanding of a parasite's defense system and alternative to the discovery
      of potent glutathione S-transferase inhibitors.
AB  - A primary pathway for metabolism of electrophilic compounds in Schistosoma
      japonicum involves glutathione S-transferase (SjGST)-catalyzed formation of
      glutathione (GSH) conjugates. As part of a program aimed at gaining a better
      understanding of the defense system of parasites, a series of aromatic halides (1
      8), aliphatic halides (9, 10), epoxides (11-20), alpha,beta-unsaturated esters
      (21, 22), and alpha,beta-unsaturated amides (23, 24) were prepared, and their
      participation in glutathione conjugate formation was evaluated. Products from
      enzymatic and nonenzymatic reactions of these substances with glutathione were
      characterized and quantified by using reverse-phase high-performance liquid
      chromatography (HPLC), NMR, and fast atom bombardment mass spectrometry (FAB-MS)
      analysis. Mechanisms for formation of specific mono(glutathionyl) or
      bis(glutathionyl) conjugates are proposed. Although the results of this effort
      indicate that SjGST does not catalyze addition or substitution reactions of 1, 3,
      4, 7-9, 11-13, 15-17, 19-21, and 24, they demonstrate that 2, 5, 6, 14, 18, and
      23 undergo efficient enzyme-catalyzed conjugation reactions. The kcat values for
      SjGST with 23 and 18 are about 886-fold and 14-fold, respectively, larger than
      that for 5. This observation suggests that 23 is a good substrate in comparison
      to other electrophiles. Furthermore, the initially formed conjugation product,
      23a, is also a substrate for SjGST in a process that forms the bis(glutathionyl)
      conjugate 23b. Products arising by enzymatic and nonenzymatic pathways are
      generated under the conditions of SjGST-activated GSH conjugation. Interestingly,
      production of nonenzymatic GSH conjugates with electrophilic substrates often
      overwhelms the activity of the enzyme. The nonenzymatic GSH conjugates, 9a-11a,
      16a, 21a, and 22a, are inhibitors of SjGST with respective IC50 values of 1.95,
      75.5, 0.96, 19.0, 152, and 0.36 microM, and they display moderate inhibitory
      activities against human GSTA2. Direct evidence has been gained for substrate
      inhibition by 10 toward SjGST and GSTA2 that is more potent than that of its GSH
      conjugate 10a. The significance of this work is found in the development of a
      convenient NMR-based technique that can be used to characterize glutathione
      conjugates derived from small molecule libraries as part of efforts aimed at
      uncovering specific potent SjGST and GSTA2 inhibitors. This method has potential
      in applications to the identification of novel inhibitors of other GST targets
      that are of chemotherapeutic interest.

PMID- 17226964
TI  - Copper-activated DNA photocleavage by a pyridine-linked bis-acridine
      intercalator.
AB  - We report the synthesis of new photonuclease 4 consisting of two acridine rings
      joined by a pyridine-based copper binding linker. We have shown that
      photocleavage of plasmid DNA is markedly enhanced when this ligand is irradiated
      in the presence of copper(II) (419 nm, 22 degrees C, pH 7.0). Viscometric data
      indicate that 4 binds to DNA by monofunctional intercalation, and equilibrium
      dialysis provides an estimated binding constant of 1.13 x 105 M-1 for its
      association with calf thymus DNA. In competition dialysis experiments, 4 exhibits
      preferential binding to GC-rich DNA sequences. When Cu(II) is added at a ligand
      to metal ratio of 1:1, electrospray ionization mass spectrometry demonstrates
      that compound 4 undergoes complex formation, while thermal melting studies show a
      10 degrees C increase in the Tm of calf thymus DNA. Groove binding and
      intercalation are suggested by viscometric data. Finally, colorimetric and
      scavenger experiments indicate that the generation of Cu(I), H2O2, and superoxide
      contributes to the production of DNA frank strand breaks by the Cu(II) complex of
      4. Whereas the strand breaks are distributed in a relatively uniform fashion over
      the four DNA bases, subsequent piperidine treatment of the photolysis reactions
      shows that alkaline labile lesions occur predominantly at guanine.

PMID- 17226965
TI  - Synthesis of cell-penetrating conjugates of calpain activator peptides.
AB  - Calpains, the intracellular proteolytic enzymes, play important roles in various
      processes in cells. The lack of calpain or its overexpression is thought to be an
      underlying factor in some diseases. In this study, we report the synthesis of a
      new group of cell-penetrating calpastatin-peptide conjugates with the activating
      capacity of m-calpain intracellularly. In these constructs, peptides related to
      the calpastatin A or C subunit with the capabiliy of activation of isolated m
      calpain was covalently conjugated to the C-terminal of penetratin via amide,
      thioether, or disulfide bond. These conjugates were prepared by solid-phase
      synthesis and/or by chemical ligation and properly characterized (MS, HPLC). Our
      results using isolated m-calpain suggest that conjugation does not interfere with
      the enzyme-activating effect of the calpastatin peptides; in fact, the efficiency
      of the conjugates was markedly higher. The conjugates with different bonds showed
      essentially the same level of activation. Internalization experiments with
      fluorophore (4-[7-hydroxycoumaryl] acetic acid (Hca) at the N-terminal of
      penetratin and/or 5(6)-carboxyfluorescein (cf)) labeled conjugates show that
      these constructs are taken up by COS-7 cells. Using cell lysates produced after
      incubation with the 1:1 (mol/mol) mixture of calpastatin A and C peptide
      conjugates, we found a significant calpain activating effect. We also noticed
      that the conjugate even with a disulfide bond between the components seems to be
      stable and activate m-calpain after intracellular translocation under the
      conditions studied. To the best of our knowledge, this is the first report to
      describe conjugates with an m-calpain activating effect on isolated enzymes and
      more importantly within living cells after transmembrane delivery. Thus, these
      conjugates seem to be appropriate as molecular tools to activate intracellular m
      calpain and to study calpain functions in living cells.

PMID- 17226966
TI  - Novel bioreducible poly(amido amine)s for highly efficient gene delivery.
AB  - A series of novel bioreducible poly(amido amine)s containing multiple disulfide
      linkages (SS-PAAs) were synthesized and evaluated as nonviral gene vectors. These
      linear SS-PAAs could be easily obtained by Michael-type polyaddition of various
      primary amines to the disulfide-containing cystamine bisacrylamide. The SS-PAA
      polymers are relatively stable in medium mimicking physiological conditions (pH
      7.4, 150 mM PBS, 37 degrees C), but are rapidly degraded in the presence of 2.5
      mM DTT, mimicking the intracellular reductive environment (pH 7.4, [R-SH] = 5 mM,
      37 degrees C). The polymers efficiently condense DNA into nanoscaled (<200 nm)
      and positively charged (>+20 mV) polyplexes that are stable under neutral
      conditions but are rapidly destabilized in a reductive environment, as was
      revealed by both dynamic light scatting measurement and agarose gel assays.
      Moreover, most of the poly(amido amine)s possess buffer capacities in the pH
      range pH 7.4-5.1 that are even higher than polyethylenimine (pEI), a property
      that may favorably contribute to the endosomal escape of the polyplexes.
      Polyplexes of four of the seven SS-PAAs studied were able to transfect COS-7
      cells in vitro with transfection efficiencies significantly higher than those of
      branched pEI, being one of the most effective polymeric gene carriers reported to
      date. Importantly, also in the presence of serum, a high level of gene expression
      could be observed when the incubation time was elongated from 1 h to 4 h. XTT
      assays showed that SS-PAAs and their polyplexes possess essentially no or only
      very low cytotoxicity at concentrations where the highest transfection activity
      is observed. The results indicate that bioreducible poly(amido amine)s have
      excellent properties for the development of highly potent and nontoxic polymeric
      gene carriers.

PMID- 17226967
TI  - Sugar-quantum dot conjugates for a selective and sensitive detection of lectins.
AB  - One-pot synthesized neoglycoconjugates with a reactive thiol group are introduced
      here for functionalization with carbohydrates for solubilization and
      stabilization of CdSe-ZnS quantum dots in aqueous solution. Three different sizes
      of quantum dots (QDs) with lactose, melibiose, and maltotriose on their surface
      have been utilized, for the first time, for lectin detection through
      agglutination assay. The sugar-QDs thus synthesized were characterized by
      transmission election microscopy (TEM), fluorescence, and absorption
      spectroscopy. Agglutination of sugar-QDs by three different lectins occurred
      through specific multivalent carbohydrate-lectin interactions and was studied
      extensively by monitoring the scattered light at 600 nm. This assay was very
      selective, which has been demonstrated by a more selective binding of soybean
      agglutinin (SBA) with melibiose-QD, as compared to lactose-QD, and specific
      deagglutination caused by alpha-d-galactose, while alpha-d-mannose did not show
      any effect. The detection sensitivity of the maltotriose-QD was tested with
      Concanavalin A (ConA), and as little as 100 nM of the lectin was detected using
      light scattering. The detection sensitivity of this protocol has been enhanced
      considerably by the fluorescence properties of QDs. This agglutination process
      seems to occur through formation of smaller soluble aggregates, which further
      associate to form larger aggregates.

PMID- 17226968
TI  - Ricin antitoxins based on lyotropic mesophases containing galactose amphiphiles.
AB  - Lyotropic mesophases of the inverse hexagonal or cubic type are nanostructured
      materials that result from the self-assembly of amphiphilic surfactant molecules
      in water. The extremely large area of the surfactant-water interface inherent
      within these structures makes them attractive media for sorbent or encapsulant
      systems. Here, we report on the development of a new class of polyvalent
      materials that are based on the incorporation of bioactive ligands within
      lyotropic mesophases. In particular, we have studied the potential for these
      materials to behave as polyvalent antitoxins by incorporating synthetic galactose
      amphiphiles, which mimic the natural cell surface ligand for the protein toxin
      ricin. The study demonstrates that cubic morphology lyotropic mesophases
      containing galactose amphiphiles exhibit high specificity ricin uptake, with
      favorably high dissociation constants and high capacities. We suggest that
      lyotropic mesophase polyvalent ligands are thus promising materials for the
      incorporation of a broad range of cell surface recognition moieties and hence may
      have wide applicability as materials capable of partaking in biological
      recognition processes.

PMID- 17226969
TI  - Sequence-specific targeting of RNA with an oligonucleotide-neomycin conjugate.
AB  - The synthesis of neomycin covalently attached at the C5-position of 2'
      deoxyuridine is reported. The synthesis outlined allows for incorporation of an
      aminoglycoside (neomycin) at any given site in an oligonucleotide (ODN) where a
      thymidine (or uridine) is present. Incorporation of this modified base into an
      oligonucleotide, which is complementary to a seven-bases-long alpha-sarcin loop
      RNA sequence, leads to enhanced duplex hybridization. The increase in Tm for this
      duplex (DeltaTm = 6 degrees C) suggests a favorable interaction of neomycin
      within the duplex groove. CD spectroscopy shows that the modified duplex adopts
      an A-type confirmation. ITC measurements indicate the additive effects of ODN and
      neomycin binding to the RNA target (Ka = 4.5 x 107 M-1). The enhanced stability
      of the hybrid duplex from this neomycin-ODN conjugate originates primarily from
      the enthalpic contribution of neomycin {DeltaDeltaHobs = -7.21 kcal/mol
      (DeltaHneomycin conjugated - DeltaH nonconjugated)} binding to the hybrid duplex.
      The short linker length allows for selective stabilization of the hybrid duplex
      over the hybrid triplex. The results described here open up new avenues in the
      design and synthesis of nucleo-aminoglycoside-conjugates (N-Ag-C) where the
      inclusion of any number of aminoglycoside (neomycin) molecules per
      oligonucleotide can be accomplished.

PMID- 17226970
TI  - Protein delivery by the cell-penetrating peptide YTA2.
AB  - In most cases, the transport of cell-penetrating peptide (CPP) with a cargo
      molecule over the plasma membrane requires a cross-linking of the cargo molecule
      to the peptide. Lately, a method of cargo delivery, coincubation with CPP, has
      been applied. We have studied uptake and toxicity of the CPP, YTA2, in the Bowes
      human melanoma cell line and human MDA-MB-231 breast cancer cell line and
      compared the results with known cell-penetrating peptides. The results show that
      fluoresceinyl YTA2 is taken up by the Bowes cells with 3.23 nmol/mg protein and
      shows low membrane toxicity to the cells with an EC50 of 60 microM. Furthermore,
      we show that YTA2 is capable of delivering cargo proteins, such as beta
      galactosidase and tetramethyl rhodamine iso-thiocyanate (TRITC) labeled
      streptavidin into cells by coincubation. The delivery of TRITC-labeled
      streptavidin was quantified to 42.4 pmol streptavidin/mg protein. The delivery of
      proteins into the cells by mere coincubation is an advantage, since the chemical
      coupling between the CPP and the cargo molecule, which adds time-consuming
      synthesis and purification steps, can be omitted. In addition, the flexibility in
      CPP cargo delivery is increased.

PMID- 17226971
TI  - Development of tissue plasminogen activator specific "on demand cleavable" (odc)
      linkers for radioimmunotherapy by screening one-bead-one-compound combinatorial
      peptide libraries.
AB  - New strategies are needed to protect normal organs from radiation in cancer
      radioimmunotherapy (RIT). This can be achieved by rapid clearance of radiometal
      in the circulation after accumulation of radioimmunoconjugates (RIC) in the
      tumor. Our strategy is to place highly efficient and specific cleavable linkers
      between radiometal chelates and the tumor targeting agents. Such linkers must be
      resistant to cleavage by enzymes present in the plasma and the tumor. After
      radiotargeting agents have accumulated in the tumor, a cleaving agent can be
      administered "on demand" to cleave a specific linker, resulting in the release of
      radiometal from the circulating RIC in a form that will have rapid renal
      clearance. We have selected TNKase, a thrombolytic agent approved for patient
      use, as our model on-demand cleaving agent. To identify TNKase-specific linkers,
      we screened fluorescent-quenched random "one-bead-one-compound" (OBOC)
      combinatorial peptide libraries. d-Amino acid containing peptides that were
      specific for TNKase but were resistant to cleavage by plasma and tumor-associated
      proteases were identified. One of these peptide substrates (rqYKYkf) was used to
      link the DOTA chelate to ChL6, a monoclonal antibody known to target breast
      cancer. This antibody conjugate was stable in plasma for 7 days while preserving
      the immunoreactivity to intact tumor cells. The addition of TNKase at clinical
      achievable plasma level (10 mug/mL) resulted in the release of 28% of the
      radiometal from the radioimmunoconjugate within 72 h. This lead linker, after
      further optimization to increase its response to TNKase, may be useful in the
      development of more effective radioimmunotherapeutic and radioimaging agents.

PMID- 17226972
TI  - Encapsulated magnetic nanoparticles as supports for proteins and recyclable
      biocatalysts.
AB  - This paper describes the bioconjugation of histidine-tagged enzymes and other
      proteins to the surface of composite "magnetomicelles" consisting of magnetic
      gamma-Fe2O3 nanoparticles encapsulated within cross-linked polystyrene-block
      polyacrylate copolymer micelle shells. Free carboxylic acid groups on the
      magnetomicelle surface were converted to Cu2+-iminodiacetic acid (IDA) for
      protein capture. The conjugation of T4 DNA ligase and enhanced green fluorescent
      protein to magnetomicelles revealed that proteins were captured with a high
      surface density and could be magnetically separated from reaction mixtures and
      subsequently released from the nanoparticle surface. Additionally, bioconjugation
      of T7 RNA polymerase yielded a functional enzyme that maintained its biological
      activity and could be recycled for up to three subsequent transcription
      reactions. We propose that protein-magnetomicelle bioconjugates are effective for
      protein bioseparation and enzymatic recycling and further strengthen the idea
      that nanoparticle surfaces have utility in protein immobilization.

PMID- 17226973
TI  - Design, synthesis, and evaluation of [188Re]organorhenium-labeled antibody
      fragments with renal enzyme-cleavable linkage for low renal radioactivity levels.
AB  - Renal localization of radiolabeled antibody fragments constitutes a problem in
      targeted imaging and radiotherapy. We have reported that Fab fragments labeled
      with 3'-[131I]iodohippuryl Nepsilon-maleoyl-lysine (HML) showed markedly low
      renal radioactivity levels even shortly after injection, due to a rapid and
      selective release of m-[131I]iodohippuric acid by the action of brush border
      enzymes. To estimate the applicability of the molecular design to metallic
      radionuclides, [188Re]tricarbonyl(cyclopentadienylcarbonate)rhenium ([188Re]CpTR
      COOH) was conjugated with Nepsilon-tert-butoxycarbonyl-glycyl-lysine or Nepsilon
      maleoyl-glycyl-lysine to prepare [188Re]CpTR-GK-Boc or [188Re]CpTR-GK. The
      cleavage of the glycyl-lysine linkage of the two compounds generates a glycine
      conjugate of [188Re]CpTR-COOH ([188Re]CpTR-Gly), which possesses in vivo
      behaviors similar to those of m-iodohippuric acid. The hydrolysis rate of the
      peptide bond in [188Re]CpTR-GK-Boc was compared with that in 3'
      [125I]iodohippuryl Nepsilon-Boc-lysine ([125I]HL-Boc) using brush border membrane
      vesicles (BBMVs) prepared from rat kidneys. [188Re]CpTR-GK was conjugated to
      thiolated Fab fragments to prepare [188Re]CpTR-GK-Fab. The biodistribution of
      radioactivity after injection of [188Re]CpTR-GK-Fab was compared with that of
      [125I]HML-Fab and [188Re]CpTR-Fab prepared by conjugating N-hydroxysuccinimidyl
      ester of [188Re]CpTR-COOH with antibody fragments. While [188Re]CpTR-GK-Boc
      liberated [188Re]CpTR-Gly in BBMVs, [125I]HL-Boc liberated m-[125I]iodohippuric
      acid at a much faster rate. In addition, although [125I]HL-Boc was hydrolyzed by
      both metalloenzymes and nonmetalloenzymes, metalloenzymes were responsible for
      the cleavage of the peptide linkage in [188Re]CpTR-GK-Boc. In biodistribution
      studies, [188Re]CpTR-GK-Fab exhibited significantly lower renal radioactivity
      levels than did [188Re]CpTR-Fab. However, the renal radioactivity levels of
      [188Re]CpTR-GK-Fab were slightly higher than those of [125I]HML-Fab. The analysis
      of urine samples collected for 6 h postinjection of [188Re]CpTR-GK-Fab showed
      that [188Re]CpTR-Gly was the major radiometabolite. In tumor-bearing mice,
      [188Re]CpTR-GK-Fab significantly reduced renal radioactivity levels without
      impairing the radioactivity levels in tumor. These findings indicate that the
      molecular design of HML can be applied to metallic radionuclides by using a
      radiometal chelate of high inertness and by designing a radiometabolite of high
      urinary excretion when released from antibody fragments following cleavage of a
      glycyl-lysine linkage. This study also indicates that a change in chemical
      structure of a radiolabel attached to a glycyl-lysine linkage significantly
      affected enzymes involved in the hydrolysis reaction. Since there are many kinds
      of enzymes that cleave a variety of peptide linkages on the renal brush border
      membrane, selection of a peptide linkage optimal to a radiometal chelate of
      interest may provide radiolabeled antibody fragments that exhibit renal
      radioactivity levels similar to those of [131I]HML-labeled ones. The in vitro
      system using BBMVs might be useful for selecting an appropriate peptide linkage.

PMID- 17226974
TI  - Applications of tailored ferrocenyl molecules as electrochemical probes of
      biochemical interactions.
AB  - The development of electrochemical probes useful for investigating the occupancy
      by other molecules of sites on complex proteins such as human serum albumin (HSA)
      is described. Ferrocenyl-(oxoethylene)-fatty acid compounds of different fatty
      acid chain length probed different binding sites on HSA. The interaction could be
      changed from one primarily with a drug binding site, when the probe was ferrocene
      methanol, to one predominantly with medium-chain fatty acid binding sites, by
      adding an (oxoethylene)-fatty acid substituents. Finally, the interaction could
      be changed to one interacting primarily with high-affinity long-chain fatty acid
      binding sites, as the fatty acid chain length in ferrocene-(oxoethylene)-fatty
      acid molecules increased. These results strongly implied that the binding could
      be further tailored by relatively simple modifications to the probe, for example,
      by changing the balance of hydrophobicity and hydrophilicity. The possibility of
      a procedure using mass-produced electrochemical cells to determine the fractional
      occupancy of different sites on HSA is demonstrated.

PMID- 17226975
TI  - Neighboring group-controlled hydrolysis: towards "designer" drug release
      biomaterials.
AB  - To give the first demonstration of neighboring group-controlled drug delivery
      rates, a series of novel, polymerizable ester drug conjugates was synthesized and
      fully characterized. The monomers are suitable for copolymerization in
      biomaterials where control of drug release rate is critical to prophylaxis or
      obviation of infection. The incorporation of neighboring group moieties differing
      in nucleophilicity, geometry, and steric bulk in the conjugates allowed the rate
      of ester hydrolysis, and hence drug liberation, to be rationally and widely
      controlled. Solutions (2.5 x 10-5 mol dm-3) of ester conjugates of nalidixic acid
      incorporating pyridyl, amino, and phenyl neighboring groups hydrolyzed according
      to first-order kinetics, with rate constants between 3.00 +/- 0.12 x 10-5 s -1
      (fastest) and 4.50 +/- 0.31 x 10- 6 s-1 (slowest). The hydrolysis was
      characterized using UV-visible spectroscopy. When copolymerized with poly(methyl
      methacrylate), free drug was shown to elute from the resulting materials, with
      the rate of release being controlled by the nature of the conjugate, as in
      solution. The controlled molecular architecture demonstrated by this system
      offers an attractive class of drug conjugate for the delivery of drugs from
      polymeric biomaterials such as bone cements in terms of both sustained, prolonged
      drug release and minimization of mechanical compromise as a result of release. We
      consider these results to be the rationale for the development of "designer" drug
      release biomaterials, where the rate of required release can be controlled by
      predetermined molecular architecture.

PMID- 17226976
TI  - Synthesis and biological evaluation of a new type of 99mtechnetium-labeled Fatty
      Acid for myocardial metabolism imaging.
AB  - Technetium-labeled fatty acids intended for myocardial metabolism imaging and the
      respective rhenium model complexes were synthesized according to the "4 + 1"
      mixed-ligand approach and investigated in vitro and in vivo. The non-radioactive
      rhenium model complexes were characterized by NMR, IR, and EA, and the
      geometrical impact of the chelate unit on the integrity of the fatty acid head
      structure was determined by single-crystal X-ray analyses. To estimate the
      diagnostic value of the 99mTc-labeled fatty acids, the compounds were
      investigated in experiments in vitro and in biodistribution studies using male
      Wistar rats. The new fatty acid tracers contain the metal core in the oxidation
      states +3, well-wrapped in a trigonal-bipyramidal coordination moiety, which is
      attached at the omega-position of a fatty acid chain. This structural feature is
      considered to be a good imitation of the well-established iodinated phenyl fatty
      acids. High heart extraction in perfused heart studies (up to 26% injected dose
      (ID)) and noticeable heart uptake of the 99mTc tracers in vivo being in the order
      of 2% ID/g at 5 min (postinjection, pi.), accompanied by a good heart to blood
      ratio of 8, confirms that the new Tc compounds are suitable as fatty acid
      tracers.

PMID- 17226977
TI  - Fluorescent ligands for the hemagglutinin of influenza A: synthesis and ligand
      binding assays.
AB  - Two fluorescent conjugates of sialic acid have been prepared, with a convenient
      synthetic route that involves preparation of an unsaturated benzyl ester by cross
      metathesis, followed by combined hydrogenation/ hydrogenolysis to provide a
      sialoside bearing a delta-carboxybutyl group, suitable for coupling with the
      chosen fluorophores. The fluorescent conjugates bound to bromelain-cleaved
      hemagglutinin (BHA) with affinities in the low microM range. Binding was
      accompanied by approximately 4.5-fold fluorescence enhancement for the dansyl
      conjugate 1 and approximately 3-fold fluorescence quenching for the pyrene
      conjugate 3.

PMID- 17226978
TI  - Fluoro-pegylated (FPEG) imaging agents targeting Abeta aggregates.
AB  - A novel approach of producing positron emission tomography (PET) imaging agents
      through the formation of bioconjugates based on a pegylation-fluorination
      strategy resulting in fluoro-pegylated (FPEG) molecules is reported. This
      approach offers a simple and easy method by which to incorporate 18F in the
      target molecule without an appreciable increase in the lipophilicity. After 18F
      labeling, this convenient approach leads to PET imaging probes binding to Abeta
      aggregates in the brain (an important factor associated with Alzheimer's disease)
      using the known core structures, such as [2-(4-dimethylaminophenyl)-vinyl]
      benzoxazol (3') or 2-phenylbenzothiazole (4). This approach appears to be
      effective in some core structures, but it cannot be uniformly applied to all
      structures.

PMID- 17226979
TI  - Self-assembled monolayers with latent aldehydes for protein immobilization.
AB  - Aldehyde functions are widely used for immobilization of biomolecules on glass
      surfaces but have found little attention for biofunctionalization of self
      assembled monolayers (SAMs) on gold, due to interference between thiol and
      aldehyde functions. This problem was recently solved by synthesis of an
      alkanethiol that carried a vicinal diol group [Jang et al. (2003) Nano Lett. 3,
      691-694]. The latter served as a latent aldehyde function that was unmasked by
      short exposure of the vicinal diol-terminated SAM to aqueous periodate. However,
      the synthesis of the new vicinal diol-terminated alkane thiol was time-consuming
      and had an overall yield of approximately 3.5%. In the present study, a general
      modular strategy was introduced by which SAM components with vicinal diol
      functions were rapidly synthesized with high yield: this was accomplished by
      amide bond formation between a SAM-forming carboxylic acid (exemplified by lipoic
      acid and 16-mercaptohexadecanoic acid) with 3-aminopropane-1,2-diol, using
      suitable protecting groups. The disulfide or free thiol group afforded SAM
      formation on gold and, after periodate oxidation of the vicinal diol functions,
      proteins were covalently bound via their lysine residues. At 1 mg/mL protein
      concentration, complete surface coverage was reached within minutes. No further
      protein was bound by nonspecific adsorption, but cognate proteins were
      specifically bound with high capacity. Pyrogallol-O-hexadecanoic acid and 10
      undecenoic acid were also coupled with 3-aminopropane-1,2-diol by amide bond
      formation, thereby producing latent aldehyde-containing SAM components for metal
      oxides and hydrogen-terminated silicon, respectively, to show the general
      usefulness of the new synthetic design.

PMID- 17226980
TI  - 3,4,6-Tri-O-acetyl-2-deoxy-2-[18F]fluoroglucopyranosyl phenylthiosulfonate: a
      thiol-reactive agent for the chemoselective 18F-glycosylation of peptides.
AB  - 3,4,5-Tri-O-acetyl-2-[18F]fluoro-2-deoxy-d-glucopyranosyl 1-phenylthiosulfonate
      (Ac3-[18F]FGlc-PTS) was developed as a thiol-reactive labeling reagent for the
      site-specific 18F-glycosylation of peptides. Taking advantage of highly
      accessible 1,3,4,6-tetra-O-acetyl-2-deoxy-2-[18F]fluoroglucopyranose, a three
      step radiochemical pathway was investigated and optimized, providing Ac3
      [18F]FGlc-PTS in a radiochemical yield of about 33% in 90 min (decay-corrected
      and based on starting [18F]fluoride). Ac3-[18F]FGlc-PTS was reacted with the
      model pentapeptide CAKAY, confirming chemoselectivity and excellent conjugation
      yields of >90% under mild reaction conditions. The optimized method was adopted
      to the 18F-glycosylation of the alphavbeta3-affine peptide c(RGDfC), achieving
      high conjugation yields (95%, decay-corrected). The alphavbeta3 binding affinity
      of the glycosylated c(RGDfC) remained uninfluenced as determined by competition
      binding studies versus 125I-echistatin using both isolated alphavbeta3 and human
      umbilical vein endothelial cells (Ki = 68 +/- 10 nM (alphavbeta3) versus Ki = 77
      +/- 4 nM (HUVEC)). The whole radiosynthetic procedure, including the preparation
      of the 18F-glycosylating reagent Ac3-[18F]FGlc-PTS, peptide ligation, and final
      HPLC purification, provided a decay-uncorrected radiochemical yield of 13% after
      a total synthesis time of 130 min. Ac3-[18F]FGlc-PTS represents a novel 18F
      labeling reagent for the mild chemoselective 18F-glycosylation of peptides
      indicating its potential for the design and development of 18F-labeled bioactive
      S-glycopeptides suitable to study their pharmacokinetics in vivo by positron
      emission tomography (PET).

PMID- 17226981
TI  - Soluble camptothecin derivatives prepared by click cycloaddition chemistry on
      functional aliphatic polyesters.
AB  - Aliphatic polyesters are of interest as biomaterials and drug-delivery vehicles,
      as their ability to degrade under physiological conditions provides a mechanism
      for both drug release and clearance of the polymer from the body. Presented here
      is the synthesis of a polyester-drug graft copolymer conjugate, enabled by click
      cycloaddition of azide-functionalized camptothecin derivatives with alkyne
      functionalized aliphatic polyesters. Further grafting of residual alkyne groups
      with azide-terminated poly(ethylene oxide) gave a water-soluble polyester
      camptothecin conjugate. Control over PEGylation and drug loading, inherent to the
      graft copolymer design, opens versatile routes to new materials with potential
      utility in polymer therapeutics.

PMID- 17226982
TI  - Direct ring conjugation of catecholamines and their immunological interactions.
AB  - Catecholamine derivatives were synthesized with potential applications as coating
      antigens in biosensors or in the raising of specific antibodies. Thioether
      bridged derivatives of the catecholamines dopamine, norepinephrine, and
      epinephrine that attach carboxylic acid functionalities directly to the aromatic
      ring via an easily incremented linker chain were synthesized by an
      electrochemical method. These derivatives were purified by convenient ion
      exchange chromatography, exact positions of conjugation determined by NMR, and a
      dopamine derivative immobilized in situ in a BIAcore surface plasmon resonance
      (SPR) biosensor and its antibody binding studied in comparison with
      immobilization via the catecholamine primary amine. Binding of an antibody raised
      to an amine-conjugated protein conjugate showed clear distinction between
      conjugations at different positions on the catecholamine, illustrating the
      importance of rational conjugate design in immunosensing of the catecholamines.

PMID- 17226983
TI  - A versatile photocleavable bifunctional linker for facile synthesis of substrate
      DNA conjugates for the selection of nucleic acid catalysts.
AB  - Covalent photocleavable attachment of small molecules or peptides to
      oligonucleotides is an integral strategic element in the selection of novel
      nucleic acid enzymes. Here, we report the synthesis of a multipurpose,
      photocleavable bifunctional linker (PCBL) suitable for nucleic acid selections
      and other biotechnology applications. PCBL contains a photocleavable O
      nitrobenzyl group flanked on one side by an N-hydroxysuccinimidyl ester (reactive
      toward primary amines) and on the other side by a sulfhydryl. To demonstrate the
      utility of PCBL, the linker was used to couple an analog of the antibiotic
      chloramphenicol (Cam) to the 5' end of an amino-modified 8-mer DNA oligo.
      Coupling was confirmed by MALDI-TOF spectrophotometry. Decoupling was performed
      by irradiating the coupled species with near-UV light (approximately 360 nm),
      regenerating the original amino-modified oligo. Ligation of the Cam-PCBL-DNA
      conjugate to random-sequence RNA generated a diversity library appropriate for
      the selection of new ribozymes that catalyze reactions involving the tethered
      substrate. Coupling and decoupling of the Cam analog from the library was
      monitored on a trilayered organomercurial polyacrylamide gel. The
      coupling/decoupling strategy described here is readily generalized to many
      combinations of macromolecules and small molecules. For example, analogs of this
      small molecule-DNA conjugate can be generated as synthons for ligation to nucleic
      acid diversity libraries during each round of novel ribozyme selections, or they
      can be immobilized onto chips for addresssably reversible microarray analysis.

PMID- 17226984
TI  - A complete microfluidic screening platform for rational protein crystallization.

PMID- 17226985
TI  - A pentanuclear manganese single-molecule magnet with a large anisotropy.

PMID- 17226986
TI  - Enzyme-responsive molecular assembly system with amylose-primer surfactants.

PMID- 17226987
TI  - Bifunctional catalysis of proton transfer at an antibody active site.

PMID- 17226988
TI  - NMR detection of protein 15N spins near paramagnetic lanthanide ions.

PMID- 17226989
TI  - Cross-bridging reaction of 5,20-diethynyl substituted hexaphyrins to vinylene
      bridged hexaphyrins.

PMID- 17226990
TI  - Azidoproline containing helices: stabilization of the polyproline II structure by
      a functionalizable group.

PMID- 17226991
TI  - Reversible cell deformation by a polymeric actuator.

PMID- 17226992
TI  - Simultaneous supralinear line-narrowing and sensitivity enhancement at high
      fields in magic angle spinning NMR of spin-1/2 nuclei in solids.

PMID- 17226993
TI  - High-accuracy distance measurement between remote methyls in specifically
      protonated proteins.

PMID- 17226994
TI  - Conformational dynamics of substrate in the active site of cytochrome P450 BM
      3/NPG complex: insights from NMR order parameters.

PMID- 17226995
TI  - Extremely strong and readily accessible AAA-DDD triple hydrogen bond complexes.

PMID- 17226996
TI  - Boron binding by a siderophore isolated from marine bacteria associated with the
      toxic dinoflagellate Gymnodinium catenatum.

PMID- 17226997
TI  - Photodelivery of nitric oxide from water-soluble platinum nanoparticles.

PMID- 17226998
TI  - A versatile strategy for quantum dot ligand exchange.

PMID- 17226999
TI  - Pentaindenocorannulene and tetraindenocorannulene: new aromatic hydrocarbon pi
      systems with curvatures surpassing that of C60.

PMID- 17227000
TI  - Intramolecular cyclobutadiene cycloaddition/cyclopropanation/thermal
      rearrangement: an effective strategy for the asymmetric syntheses of
      pleocarpenene and pleocarpenone.

PMID- 17227001
TI  - Ultralarge and thermally stable electro-optic activities from supramolecular self
      assembled molecular glasses.

PMID- 17227002
TI  - Synthesis of potent bicyclic bisarylimidazole c-Jun N-terminal kinase inhibitors
      by catalytic C-H bond activation.

PMID- 17227003
TI  - Lewis Acid-promoted intermolecular acetal-initiated cationic polyene
      cyclizations.

PMID- 17227004
TI  - Low-temperature heck reactions of axially chiral o-iodoacrylanilides occur with
      chirality transfer: implications for catalytic asymmetric heck reactions.

PMID- 17227005
TI  - Catalytic enantioselective allenylation reactions of aldehydes with tethered
      bis(8-quinolinolato) (TBOx) chromium complex.

PMID- 17227006
TI  - Total synthesis of (+/-)-merrilactone A via catalytic Nazarov cyclization.

PMID- 17227007
TI  - Catalytic enantioselective Mannich-type reactions of ketoimines.

PMID- 17227008
TI  - Intermolecular chirality transfer from silicon to carbon: interrogation of the
      two-silicon cycle for Pd-catalyzed hydrosilylation by stereoisotopochemical
      crossover.

PMID- 17227009
TI  - A conformational switch to beta-sheet structure in cytochrome c leads to heme
      exposure. Implications for cardiolipin peroxidation and apoptosis.

PMID- 17227010
TI  - Unusual mechanical performance of amphiphilic crosslinked polymer networks.

PMID- 17227011
TI  - Spirastrellolide B reveals the absolute configuration of the spirastrellolide
      macrolide core.

PMID- 17227012
TI  - Enantioselective synthesis and structure revision of solandelactone E.

PMID- 17227013
TI  - Design of a functional membrane protein by engineering a heme-binding site in
      glycophorin A.
AB  - We have designed a functional model membrane protein by engineering a bis
      Histidine heme-binding site into a natural membrane protein, glycophorin A (GpA),
      structurally characterized by the dimerization of a single transmembrane helix.
      Out of the 32 residues comprising the transmembrane helix of GpA, five amino
      acids were mutated; the resulting protein, ME1, has been characterized in dodecyl
      phosphocholin (DPC) micelles by UV-vis, CD spectroscopy, gel electrophoresis, and
      analytical ultracentrifugation. ME1 binds heme with sub-micromolar affinity and
      maintains the highly helical secondary structure and dimeric oligomerization
      state of GpA. The ME1-Heme complex exhibits a redox potential of -128 +/- 2 mV vs
      SHE, indicating that the heme resides in a hydrophobic environment and is well
      shielded from the aqueous phase. Moreover, ME1 catalyzes the hydrogen peroxide
      dependent oxidation of organic substrates such as TMB (2,2',5,5'-tetramethyl
      benzidine). This protein may provide a useful framework to investigate how the
      protein matrix tunes the cofactor properties in membrane proteins.

PMID- 17227014
TI  - Effect of the methionine ligand on the reorganization energy of the type-1 copper
      site of nitrite reductase.
AB  - Copper-containing nitrite reductase harbors a type-1 and a type-2 Cu site. The
      former acts as the electron acceptor site of the enzyme, and the latter is the
      site of catalytic action. The effect of the methionine ligand on the
      reorganization energy of the type-1 site was explored by studying the electron
      transfer kinetics between NiR (wild type (wt) and the variants Met150Gly and
      Met150Thr) with Fe(II)EDTA and Fe(II)HEDTA. The mutations increased the
      reorganization energy by 0.3 eV (30 kJ mol-1). A similar increase was found from
      pulse radiolysis experiments on the wt NIR and three variants (Met150Gly,
      Met150His, and Met150Thr). Binding of the nearby Met62 to the type-1 Cu site in
      Met150Gly (under influence of an allosteric effector) lowered the reorganization
      energy back to approximately the wt value. According to XRD data the structure of
      the reduced type-1 site in Met150Gly NiR in the presence of an allosteric
      effector is similar to that in the reduced wt NiR (solved to 1.85 A), compatible
      with the similarity in reorganization energy.

PMID- 17227015
TI  - Interactions of 1-methylimidazole with UO2(CH3CO2)2 and UO2(NO3)2: structural,
      spectroscopic, and theoretical evidence for imidazole binding to the uranyl ion.
AB  - The first definitive high-resolution single-crystal X-ray structure for the
      coordination of the 1-methylimidazole (Meimid) ligand to UO2(Ac)2 (Ac = CH3CO2)
      is reported. The crystal structure evidence is confirmed by IR, Raman, and UV-vis
      spectroscopic data. Direct participation of the nitrogen atom of the Meimid
      ligand in binding to the uranium center is confirmed. Structural analysis at the
      DFT (B3LYP) level of theory showed a conformational difference of the Meimid
      ligand in the free gas-phase complex versus the solid state due to small
      energetic differences and crystal packing effects. Energetic analysis at the MP2
      level in the gas phase supported stronger Meimid binding over H2O binding to both
      UO2(Ac)2 and UO2(NO3)2. In addition, self-consistent reaction field COSMO
      calculations were used to assess the aqueous phase energetics of combination and
      displacement reactions involving H2O and Meimid ligands to UO2R2 (R = Ac, NO3).
      For both UO2(NO3)2 and UO2(Ac)2, the displacement of H2O by Meimid was predicted
      to be energetically favorable, consistent with experimental results that suggest
      Meimid may bind uranyl at physiological pH. Also, log(Knitrate/KAc) calculations
      supported experimental evidence that the binding stoichiometry of the Meimid
      ligand is dependent upon the nature of the reactant uranyl complex. These results
      clearly demonstrate that imidazole binds to uranyl and suggest that binding of
      histidine residues to uranyl could occur under normal biological conditions.

PMID- 17227016
TI  - Following photoinduced dynamics in bacteriorhodopsin with 7-fs impulsive
      vibrational spectroscopy.
AB  - Sub-10-fs laser pulses are used to impulsively photoexcite bacteriorhodopsin (BR)
      suspensions and probe the evolution of the resulting vibrational wave packets.
      Fourier analysis of the spectral modulations induced by transform-limited as well
      as linearly chirped excitation pulses allows the delineation of excited- and
      ground-state contributions to the data. On the basis of amplitude and phase
      variations of the modulations as a function of the dispersed probe wavelength,
      periodic modulations in absorption above 540 nm are assigned to ground-state
      vibrational coherences induced by resonance impulsive Raman spectral activity
      (RISRS). Probing at wavelengths below 540 nm-the red edge of the intense excited
      state absorption band-uncovers new vibrational features which are accordingly
      assigned to wave packet motions along bound coordinates on the short-lived
      reactive electronic surface. They consist of high- and low-frequency shoulders
      adjacent to the strong C=C stretching and methyl rock modes, respectively, which
      have ground-state frequencies of 1008 and 1530 cm-1. Brief activity centered at
      approximately 900 cm-1, which is characteristic of ground-state HOOP modes, and
      strong modulations in the torsional frequency range appear as well. Possible
      assignments of the bands and their implication to photoinduced reaction dynamics
      in BR are discussed. Reasons for the absence of similar signatures in the pump
      probe spectral modulations at longer probing wavelengths are considered as well.

PMID- 17227017
TI  - Electrostatics and color: massive electrostatic perturbation of chromophores by
      ion cluster ligands.
AB  - The SASAPOS protocol, a general reaction sequence allowing complete exchange of
      various neutral ligands X in organic, elementorganic, and inorganic systems by
      cationic ligands L+, has been applied to a variety of pentafluorophenyl
      substituted dyes of the general formula C6F5-X=Y-D (X, Y = N, CH; D = donor
      substituted arene), yielding the corresponding polycationically substituted dyes.
      The perturbation of the chromophores by the massive electrostatic effects
      introduced via the SASAPOS method led to bathochromic shifts of the absorption
      maxima of up 140 nm, 7600 cm-1, respectively. A strong dependency of the specific
      shifts on the nature of the connecting pi linker -X=Y- (N vs CH) has been
      detected by UV-vis absorption spectroscopy. Additionally, the effects of
      resubstitution of cationic ligands L+ by OH and O- have been studied.

PMID- 17227018
TI  - A fluorescence-based synthetic LPS sensor.
AB  - For the detection of bioanalytes, there is an ongoing search for synthetic
      sensors to replace enzyme-based assays which are sensitive to contaminants or
      suboptimal storage conditions. Lipopolysaccharide (LPS), a bacteria-borne
      endotoxin that may lead to life-threatening conditions such as septic shock, is
      one such case. Fluorescently labeled analogues of two peptide variants derived
      from the putative ligand-binding domain of the LPS-binding protein CD14 were
      developed that detect and discriminate LPS and lipids down to the submicromolar
      concentration range. Peptides are terminally labeled with carboxyfluorescein and
      tetramethylrhodamine. For one given peptide, sensitivity and specificity for the
      detection of LPS and discrimination from other lipids are achieved by spectral
      signatures that combine changes in the fluorescence resonance energy transfer
      (FRET) between both dyes and the total emission of tetramethylrhodamine.
      Alternatively, specificity is obtained by combining the FRET efficiencies of both
      peptide variants. In comparison to published synthetic LPS sensors, the CD14
      derived sensors yield an increase in sensitivity by about 3 orders of magnitude
      and exhibit specificity for analytes for which the design of synthetic
      recognition elements is a challenging task. Moreover, one of the sensors enabled
      the detection of LPS in the presence of up to 50% fetal calf serum, thereby
      demonstrating the feasibility of this peptide-based approach for clinically
      relevant samples.

PMID- 17227019
TI  - Catalytic intermolecular amination of C-H bonds: method development and
      mechanistic insights.
AB  - Reaction methodology for intermolecular C-H amination of benzylic and 3 degrees C
      H bonds is described. This process uses the starting alkane as the limiting
      reagent, gives optically pure tetrasubstituted amines through stereospecific
      insertion into enantiomeric 3 degrees centers, displays high chemoselectivity for
      benzylic oxidation, and enables the facile preparation of isotopically enriched
      15N-labeled compounds. Access to substituted amines, amino alcohols, and diamines
      is thereby made possible in a single transformation. Important information
      relevant to understanding the initial steps in the catalytic cycle, reaction
      chemoselectivity, the nature of the active oxidant, and pathways for catalyst
      inactivation has been gained through mechanistic analysis; these studies are also
      presented.

PMID- 17227020
TI  - Investigation of proton transport tautomerism in clusters of protonated nucleic
      acid bases (cytosine, uracil, thymine, and adenine) and ammonia by high-pressure
      mass spectrometry and ab initio calculations.
AB  - The energetics of the ion-molecule interactions and structures of the clusters
      formed between protonated nucleic acid bases (cytosine, uracil, thymine, and
      adenine) and ammonia have been studied by pulsed ionization high-pressure mass
      spectrometry (HPMS) and ab initio calculations. For protonated cytosine, uracil,
      thymine, and adenine with ammonia, the measured enthalpies of association with
      ammonia are -21.7, -27.9, -22.1, and -17.5 kcal mol-1, respectively. Different
      isomers of the neutral and protonated nucleic acid bases as well as their
      clusters with ammonia have been investigated at the B3LYP/6-31+G(d,p) level of
      theory, and the corresponding binding energetics have also been obtained. The
      potential energy surfaces for proton transfer and interconversion of the clusters
      of protonated thymine and uracil with ammonia have been constructed. For
      cytosine, the experimental binding energy is in agreement with the computed
      binding energy for the most stable isomer, CN01-01, which is derived from the
      enol form of protonated cytosine, CH01, and ammonia. Although adenine has a
      proton affinity similar to that of cytosine, the binding energy of protonated
      adenine to ammonia is much lower than that for protonated cytosine. This is shown
      to be due to the differing types of hydrogen bonds being formed. Similarly,
      although uracil and thymine have similar structures and proton affinities, the
      binding energies between the protonated species and ammonia are different.
      Strikingly, the addition of a single methyl group, in going from uracil to
      thymine, results in a significant structural change for the most stable isomers,
      UN01-01 and TN03-01, respectively. This then leads to the difference in their
      measured binding energies with ammonia. Because thymine is found only in DNA
      while uracil is found in RNA, this provides some potential insight into the
      difference between uracil and thymine, especially their interactions with other
      molecules.

PMID- 17227021
TI  - Control of mesoporous silica nanostructures and pore-architectures using a
      thickener and a gelator.
AB  - A chiral cationic thickener l-ValPyBr, which was able to enhance the viscosity of
      water and form loosely physical gel in mixtures of water and alcohols, was
      synthesized. Sol-gel polymerization of TEOS was carried out in mixtures of water
      and alcohols under basic conditions using the self-assemblies of l-ValPyBr as
      template. The left-handed twisted mesoporous silica nanoribbons, which were
      constructed by nanotubes in monolayer, were obtained, and they tended to self
      assemble into bundle structure. Stirring under the preparation process played an
      important role in the formation of this bundle structure. The obtained silica
      nanoribbons were uniform in width, thickness, and helical pitch without combining
      amorphous particles. The helical pitch and pore size of the mesoporous silica
      nanoribbons sensitively depended on the volume ratio of alcohols to water in the
      reaction mixtures. With increasing volume ratio of alcohols to water in the
      reaction mixture, the morphologies of the obtained silica changed from left
      handed twisted ribbon to coiled ribbon, then to tubular structure. A compound l
      ValPyPF6, structurally related to thickener l-ValPyBr, was able to form physical
      gel in ethanol, THF, acetonitrile, and the mixtures of ethanol and water. Left
      handed multiple helical mesoporous silica nanofibers were prepared by using the
      self-assemblies of l-ValPyPF6 as template in mixtures of water and alcohols under
      basic conditions. By controlling both the volume ratio of ethanol to water and
      the weight ratio of l-ValPyPF6 to TEOS, two- or three-dimensional pore
      architecture constructed by porous chiral nanotubes was obtained.

PMID- 17227022
TI  - Ultrafast and ultraslow oxygen atom transfer reactions between late metal
      centers.
AB  - Oxotrimesityliridium(V), (mes)3Ir=O (mes = 2,4,6-trimethylphenyl), and
      trimesityliridium(III), (mes)3Ir, undergo extremely rapid degenerate intermetal
      oxygen atom transfer at room temperature. At low temperatures, the two complexes
      conproportionate to form (mes)3Ir-O-Ir(mes)3, the 2,6-dimethylphenyl analogue of
      which has been characterized crystallographically. Variable-temperature NMR
      measurements of the rate of dissociation of the mu-oxo dimer combined with
      measurements of the conproportionation equilibrium by low-temperature optical
      spectroscopy indicate that oxygen atom exchange between iridium(V) and
      iridium(III) occurs with a rate constant, extrapolated to 20 degrees C, of 5 x
      107 M-1 s-1. The oxotris(imido)osmium(VIII) complex (ArN)3Os=O (Ar = 2,6
      diisopropylphenyl) also undergoes degenerate intermetal atom transfer to its
      deoxy partner, (ArN)3Os. However, despite the fact that its metal-oxygen bond
      strength and reactivity toward triphenylphosphine are nearly identical to those
      of (mes)3Ir=O, the osmium complex (ArN)3Os=O transfers its oxygen atom 12 orders
      of magnitude more slowly to (ArN)3Os than (mes)3Ir=O does to (mes)3Ir (kOsOs =
      1.8 x 10-5 M-1 s-1 at 20 degrees C). Iridium-osmium cross-exchange takes place at
      an intermediate rate, in quantitative agreement with a Marcus-type cross
      relation. The enormous difference between the iridium-iridium and osmium-osmium
      exchange rates can be rationalized by an analogue of the inner-sphere
      reorganization energy. Both Ir(III) and Ir(V) are pyramidal and can form
      pyramidal iridium(IV) with little energetic cost in an orbitally allowed linear
      approach. Conversely, pyramidalization of the planar tris(imido)osmium(VI)
      fragment requires placing a pair of electrons in an antibonding orbital. The
      unique propensity of (mes)3Ir=O to undergo intermetal oxygen atom transfer allows
      it to serve as an activator of dioxygen in cocatalyzed oxidations, for example,
      acting with osmium tetroxide to catalyze the aerobic dihydroxylation of
      monosubstituted olefins and selective oxidation of allyl and benzyl alcohols.

PMID- 17227023
TI  - Investigating the molecular mechanisms of in-plane mechanochemistry on cantilever
      arrays.
AB  - Free-standing cantilevers, which directly translate specific biochemical
      reactions into micromechanical motion, have recently attracted much attention as
      label-free biosensors and micro/nano robotic devices. To exploit this
      mechanochemical sensing technology, it is essential to develop a fundamental
      understanding of the origins of surface stress. Here we report a detailed study
      into the molecular basis of stress generation in aqueous environments focusing on
      the pH titration of model mercaptohexadecanoic acid self-assembled monolayers
      (SAMs), using in situ reference cantilevers coated with nonionizable
      hexadecanethiol SAMs. Semiautomated data analysis and a statistical model were
      developed to quantify cyclic deprotonation/protonation reactions on multiple
      arrays. In-plane force titrations were found to have the sensitivity to detect
      ionic hydrogen bond formation between protonated and nonprotonated carboxylic
      acid groups in the proximity of the surface pK1/2, which generated a mean tensile
      differential surface stress of +1.2 +/- 0.3 mN/m at pH 6.0, corresponding to 1 pN
      attractive force between two adjacent MHA molecules. Conversely, the magnitude of
      compressive differential surface stress was found to increase progressively with
      pH >/= 7.0, reaching a maximum of -14.5 +/- 0.5 mN/m at pH 9.0, attributed to
      enhanced electrostatic repulsion between deprotonated carboxylic acid groups.
      However, striking differences were observed in the micromechanical responses to
      different ionic strength and ion species present in the aqueous environment,
      highlighting the critical role of counter- and co-ions on surface stress. Our
      findings provide fundamental insights into the molecular mechanisms of in-plane
      mechanochemistry, which may be exploited for biosensing and nanoactuation
      applications.

PMID- 17227024
TI  - CT-CT annihilation in rigid perylene end-capped pentaphenylenes.
AB  - The time-dependent spectral properties of a rigid, extended system consisting of
      three pentaphenylene units end-capped with perylene monoimide were investigated
      in detail by femtosecond transient absorption and single photon timing
      measurements. In polar solvents, the molecular system shows the occurrence of
      photoinduced charge transfer. Upon gradually increasing the excitation power,
      annihilation involving two states with charge-transfer character has been
      observed. Quantum-chemical calculations performed on the system consisting of two
      pentaphenylene units end-capped with perylene monoimide strongly support the
      experimental data.

PMID- 17227025
TI  - Near-infrared (NIR) to red and green up-conversion emission from silica sol-gel
      thin films made with La(0.45)Yb(0.50)Er(0.05)F(3) nanoparticles, hetero-looping
      enhanced energy transfer (Hetero-LEET): a new up-conversion process.
AB  - Bright green and red luminescence has been generated with a 980 nm diode laser
      from silica sol-gel thin films made with La0.45Yb0.50Er0.05F3 nanoparticles
      through a newly described hetero-looping-enhanced energy-transfer (hetero-LEET)
      up-conversion process, which exhibits a power dependence similar to that of a
      photon avalanche (PA). The hetero-LEET mechanism is potentially more efficient
      than PA, ground-state absorption/excited-state absorption (GSA/ESA), and energy
      transfer (ETU) mechanisms because it combines resonant ground-state absorption
      with a looping or feedback process.

PMID- 17227026
TI  - Design and optimization of molecular nanovalves based on redox-switchable
      bistable rotaxanes.
AB  - Redox-controllable molecular nanovalves based on mesoporous silica nanoparticles
      have been fabricated, using two bistable [2]rotaxanes with different spacer
      lengths between their recognition sites as the gatekeepers. Three different
      linkers with varying chain lengths have been employed to attach the bistable
      [2]rotaxane molecules covalently to the silica substrate. These nanovalves can be
      classified as having IN or OUT locations, based on the positions of the tethered
      bistable [2]rotaxanes with respect to the entrances to the nanopores. The
      nanovalves are more efficient when the bistable [2]rotaxane-based gatekeepers are
      anchored deep within (IN) the pores than when they are attached closer to (OUT)
      the pores' orifices. The silica nanopores can be closed and opened by moving the
      mechanically interlocked ring component of the bistable [2]rotaxane closer to and
      away from the pores' orifices, respectively, a process which allows luminescent
      probe molecules, such as coumarins, tris(2-phenylpyridine)iridium, and rhodamine
      B, to be loaded into or released from the mesoporous silica substrate on demand.
      The lengths of the linkers between the surface and the rotaxane molecules also
      play a critical role in determining the effectiveness of the nanovalves. The
      shorter the linkers, the less leaky are the nanovalves. However, the distance
      between the recognition units on the rod section of the rotaxane molecules does
      not have any significant influence on the nanovalves' leakiness. The controlled
      release of the probe molecules was investigated by measuring their luminescence
      intensities in response to ascorbic acid, which induces the ring's movement away
      from the pores' orifices, and consequently opens the nanovalves.

PMID- 17227027
TI  - Analysis of PUGNAc and NAG-thiazoline as transition state analogues for human O
      GlcNAcase: mechanistic and structural insights into inhibitor selectivity and
      transition state poise.
AB  - O-GlcNAcase catalyzes the cleavage of beta-O-linked 2-acetamido-2-deoxy-beta-d
      glucopyranoside (O-GlcNAc) from serine and threonine residues of post
      translationally modified proteins. Two potent inhibitors of this enzyme are O-(2
      acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) and 1,2
      dideoxy-2'-methyl-alpha-d-glucopyranoso[2,1-d]-Delta2'-thiazoline (NAG
      thiazoline). Derivatives of these inhibitors differ in their selectivity for
      human O-GlcNAcase over the functionally related human lysosomal beta
      hexosamindases, with PUGNAc derivatives showing modest selectivities and NAG
      thiazoline derivatives showing high selectivities. The molecular basis for this
      difference in selectivities is addressed as is how well these inhibitors mimic
      the O-GlcNAcase-stabilized transition state (TS). Using a series of substrates,
      ground state (GS) inhibitors, and transition state mimics having analogous
      structural variations, we describe linear free energy relationships of
      log(KM/kcat) versus log(KI) for PUGNAc and NAG-thiazoline. These relationships
      suggest that PUGNAc is a poor transition state analogue, while NAG-thiazoline is
      revealed as a transition state mimic. Comparative X-ray crystallographic analyses
      of enzyme-inhibitor complexes reveal subtle molecular differences accounting for
      the differences in selectivities between these two inhibitors and illustrate key
      molecular interactions. Computational modeling of species along the reaction
      coordinate, as well as PUGNAc and NAG-thiazoline, provide insight into the
      features of NAG-thiazoline that resemble the transition state and reveal where
      PUGNAc fails to capture significant binding energy. These studies also point to
      late transition state poise for the O-GlcNAcase catalyzed reaction with
      significant nucleophilic participation and little involvement of the leaving
      group. The potency of NAG-thiazoline, its transition state mimicry, and its lack
      of traditional transition state-like design features suggest that potent
      rationally designed glycosidase inhibitors can be developed that exploit
      variation in transition state poise.

PMID- 17227028
TI  - Highly selective Diels-Alder reactions of directly connected enyne dienophiles.
AB  - The paper describes the course of cycloadditions of Diels-Alder dienophiles
      containing linked enyne sites, each substituted with activating groups.
      Consistently, it was found that in the enyne cases the Diels-Alder reaction
      occurred specifically at the acetylenic center. Furthermore, it was found that
      the regiochemical sense of the cycloaddition was apparently determined by the
      remote activating group bound to the olefinic site. This remote acrylyl group
      totally dominated the course of the cycloaddition, relative to the activating
      group bound directly on the acetylene site. Explanations for these findings at
      the computational level are provided. The computations also rationalize the
      strong preference for cycloaddition to occur at the acetylene linkage and
      encompass the otherwise surprising regiochemical dominance by the remote ester on
      the olefinic site. The high selectivities available through such reactions
      provide important new opportunities in the synthesis of orsenillate type
      substructures that are found in a variety of natural products of contemporary
      interest.

PMID- 17227029
TI  - Design of sandwichlike complexes based on the planar tetracoordinate carbon unit
      CAl4(2-).
AB  - Ever being a large curiosity, a series of simple "planar tetracoordinate carbon
      (ptC)" molecules have been recently characterized by experiments. Incorporation
      of such exotic ptC units into the assembled molecular materials, which will
      bridge the isolated clusters in molecular beams and the potential solid
      materials, is very challenging. In this paper, we described the first attempt on
      how to assemble the fewest-number ptC unit CAl42- into molecular materials in
      sandwich forms on the basis of the density functional theory calculations on a
      series of model compounds [D(CAl4)M]q- as well as the saturated compounds
      [D(CAl4)Mn] ((D = CAl42-, Cp-(C5H5-); M = Li, Na, K, Be, Mg, Ca). For M = Li, Be,
      Mg, and Ca, the ptC unit CAl42- can only be assembled in our newly proposed
      "heterodecked sandwich" scheme (e.g., [Cp(CAl4)M]q- (M = Li, Na, K, q = 2; M =
      Be, Mg, Ca, q = 1)) so as to avoid cluster fusion. For M = Na and K, the ptC unit
      CAl42- can be assembled in both the traditional "homodecked sandwich" [(CAl4)2M]q
      (M = Li, Na, K, q = 3; M = Be, Mg, Ca, q = 2) and the novel heterodecked
      sandwich schemes. Moreover, the counterions were found to have an important role
      in determining the type of the ground structures for the homodecked sandwich.
      Various assembled species in extended frameworks were designed. Notably, among
      all the designed sandwich species, the ptC unit CAl42- generally prefers to
      interact with the partner deck at the side (Al-Al bond) or corner (Al atom) site.
      This has not been reported in the sandwich complexes on the basis of the known
      decks such as Cp-, P5-, N42-, and Al42-, for which only the traditional face-face
      interaction type was considered. Our results for the first time showed that the
      ptC unit CAl42- can act as a new type of "superatom". The present results are
      expected to enrich the flat carbon chemistry, superatom chemistry, metallocenes,
      and combinational chemistry.

PMID- 17227030
TI  - Photon-induced selective interaction between small-diameter metallic carbon
      nanotubes and triton X-100.
AB  - We report a highly selective chemical interaction between single-walled carbon
      nanotubes and Triton X-100 according to nanotubes' electronic structure and
      diameter. The interaction is induced by laser irradiation at power densities down
      to 10-2 microW/microm2 but with photon energies matching those for electronic
      transition in nanotubes. Our experimental results point to a photon-induced
      chemical interaction of Triton X-100 with metallic nanotubes below 1.1 nm in
      diameter and indicate the selectivity being dictated by Fermi electrons and
      enhanced by curvature-induced strain.

PMID- 17227031
TI  - End-to-end vs interior loop formation kinetics in unfolded polypeptide chains.
AB  - The conformational search for favorable intramolecular interactions during
      protein folding is limited by intrachain diffusion processes. Recent studies on
      the dynamics of loop formation in unfolded polypeptide chains have focused on
      loops involving residues near the chain ends. During protein folding, however,
      most contacts are formed between residues in the interior of the chain. We
      compared the kinetics of end-to-end loop formation (type I loops) to the
      formation of end-to-interior (type II loops) and interior-to-interior loops (type
      III loops) using triplet-triplet energy transfer from xanthone to
      naphthylalanine. The results show that formation of type II and type III loops is
      slower compared to type I loops of the same size and amino acid sequence. The
      rate constant for type II loop formation decreases with increasing overall chain
      dimensions up to a limiting value, at which loop formation is about 2.5-fold
      slower for type II loops compared to type I loops. Comparing type II loops of
      different loop size and amino acid sequence shows that the ratio of loop
      dimension over total chain dimension determines the rate constant for loop
      formation. Formation of type III loops is 1.7-fold slower than formation of type
      II loops, indicating that local chain motions are strongly coupled to motions of
      other chain segments which leads to faster dynamics toward the chain ends. Our
      results show that differences in the kinetics of formation of type I, type II,
      and type III loops are mainly caused by differences in internal flexibility at
      the different positions in the polypeptide chain. Interactions of the polypeptide
      chain with the solvent contribute to the kinetics of loop formation, which are
      strongly viscosity-dependent. However, the observed differences in the kinetics
      of formation of type I, type II, and type III loops are not due to the increased
      number of peptide-solvent interactions in type II and type III loops compared to
      type I loops as indicated by identical viscosity dependencies for the kinetics of
      formation of the different types of loops.

PMID- 17227032
TI  - J-GFT NMR for precise measurement of mutually correlated nuclear spin-spin
      couplings.
AB  - G-matrix Fourier transform (GFT) NMR spectroscopy is presented for accurate and
      precise measurement of chemical shifts and nuclear spin-spin couplings correlated
      according to spin system. The new approach, named "J-GFT NMR", is based on a
      largely extended GFT NMR formalism and promises to have a broad impact on
      projection NMR spectroscopy. Specifically, constant-time J-GFT (6,2)D (HA-CA-CO)
      N-HN was implemented for simultaneous measurement of five mutually correlated NMR
      parameters, that is, 15N backbone chemical shifts and the four one-bond spin-spin
      couplings 13Calpha-1Halpha, 13Calpha-13C', 15N-13C', and 15N-1HNu. The experiment
      was applied for measuring residual dipolar couplings (RDCs) in an 8 kDa protein Z
      domain aligned with Pf1 phages. Comparison with RDC values extracted from
      conventional NMR experiments reveals that RDCs are measured with high precision
      and accuracy, which is attributable to the facts that (i) the use of constant
      time evolution ensures that signals do not broaden whenever multiple RDCs are
      jointly measured in a single dimension and (ii) RDCs are multiply encoded in the
      multiplets arising from the joint sampling. This corresponds to measuring the
      couplings multiple times in a statistically independent manner. A key feature of
      J-GFT NMR, i.e., the correlation of couplings according to spin systems without
      reference to sequential resonance assignments, promises to be particularly
      valuable for rapid identification of backbone conformation and classification of
      protein fold families on the basis of statistical analysis of dipolar couplings.

PMID- 17227033
TI  - Zinc-zinc bonded zincocene structures. Synthesis and characterization of Zn2(eta5
      C5Me5)2 and Zn2(eta5-C5Me4Et)2.
AB  - While, in general, decamethylzincocene, Zn(C5Me5)2, and other zincocenes,
      Zn(C5Me4R)2 (R = H, But, SiMe3), react with dialkyl and diaryl derivatives,
      ZnR'2, to give the half-sandwich compounds (eta5-C5Me4R)ZnR', under certain
      conditions the reactions of Zn(C5Me5)2 with ZnEt2 or ZnPh2 produce unexpectedly
      the dizincocene Zn2(eta5-C5Me5)2 (1) in low yields, most likely as a result of
      the coupling of two (eta5-C5Me5)Zn* radicals. An improved, large scale (ca. 2 g)
      synthesis of 1 has been achieved by reduction of equimolar mixtures of Zn(C5Me5)2
      and ZnCl2 with KH in tetrahydrofuran. The analogous reduction of Zn(C5Me4R)2 (R =
      H, SiMe3, But) yields only decomposition products, but the isotopically labeled
      dimetallocene 68Zn2(eta5-C5Me5)2 and the related compound Zn2(eta5-C5Me4Et)2 (2)
      have been obtained by this procedure. Compound 2 has lower thermal stability than
      1, but it has been unequivocally characterized by low-temperature X-ray
      diffraction studies. As for 1 a combination of structural characterization
      techniques has provided unambiguous evidence for its formulation as the Zn-Zn
      bonded dimer Zn2(eta5-C5Me4Et)2, with a short Zn-Zn bond of 2.295(3) A indicative
      of a strong Zn-Zn bonding interaction. The electronic structure and the bonding
      properties of 1 and those of related dizincocenes Zn2(eta5-Cp')2 have been
      studied by DFT methods (B3LYP level), with computed bond distances and angles for
      dizincocene 1 very similar to the experimental values. The Zn-Zn bond is strong
      (ca. 62 kcal.mol-1 for 1) and resides in the HOMO-4, that has a contribution of
      Zn orbitals close to 60%, consisting mostly of the Zn 4s orbitals (more than
      96%).

PMID- 17227034
TI  - Supramolecular PEG-co-oligo(p-benzamide)s prepared on a peptide synthesizer.
AB  - An automated synthesis protocol has been developed for the preparation of oligo(p
      benzamide)s on solid support using a commercial peptide synthesizer employing a
      variation of standard Fmoc chemistry. Bis(trichloromethyl carbonate) in NMP was
      used to activate the aromatic carboxylic acids for acylation of secondary
      aromatic amines on solid support. N-Protected hepta(p-benzamide) was
      automatically prepared on solid support and manually converted to a solid
      supported block co-oligomer by attaching a poly(ethylene glycol) chain. Cleavage
      from the support could be achieved with minimal loss of the p-methoxybenzyl N
      protective group. While the N-protected block co-oligomer was molecularly
      dissolved in nonpolar organic solvents, the N-deprotected block co-oligomer
      adopted a rod-coil conformation and showed strong aggregation as evidenced by gel
      permeation chromatography and transmission electron microscopy. Rigid rodlike
      aggregates could be observed in chloroform, toluene, as well as water.

PMID- 17227035
TI  - Engineering copper sites in proteins: loops confer native structures and
      properties to chimeric cupredoxins.
AB  - The ligand-containing loops of two copper-binding electron-transfer proteins
      (cupredoxins) have been swapped. In the azurin (AZ) variant in which the
      plastocyanin (PC) sequence is introduced (AZPC), the loop adopts a conformation
      identical to that in PC. The reduction potential of AZPC is raised as compared to
      AZ and matches that of PC. In the previously published AZAMI variant (AMI =
      amicyanin), the shorter introduced loop adopts the same conformation as in AMI,
      and the reduction potential is lowered to equal that of AMI (Yanagisawa, S.;
      Dennison, C. J. Am. Chem. Soc. 2004, 126, 15711-15719. Li, C.; et al. Proc. Natl.
      Acad. Sci. U.S.A. 2006, 103, 7258-7263). Thus, the loop structure plays an
      important role in tuning the reduction potential of a type 1 copper site with
      contributions from protein dipoles in this region probably the most important
      feature. The structure of the loop also seems to be a major factor in controlling
      dissociation and protonation of the C-terminal His ligand, which can act as a
      switch to regulate electron-transfer reactivity. The PCAZ variant (PC with the AZ
      loop) possesses an active site, which is different from those of both PC and AZ,
      and it is assumed that the introduced loop does not adopt a structure as in AZ.
      This contributes to the observed instability of PCAZ and highlights that loop
      scaffold interactions are important for stabilizing the active site of a
      cupredoxin.

PMID- 17227036
TI  - Formation of water-dispersible nanotubular graphitic assembly decorated with
      isothiouronium ion groups and its supramolecular functionalization.
AB  - A newly designed Gemini-shaped hexabenzocoronene amphiphile (1), carrying an
      isothiouronium ion-appended side chain, self-assembles in CH2Cl2 to form a
      nanotubular object, whose graphitic wall is densely covered by a positively
      charged molecular layer of isothiouronium ion pendants. The graphitic nanotube
      can be dispersed uniformly in aqueous media owing to effective hydration as well
      as electrostatic repulsion. Post-supramolecular functionalization of the nanotube
      surface is possible, without disruption of the tubular morphology, by taking
      advantage of a specific interaction of the isothiouronium ion pendants with
      oxoanion guests. Mixing with sodium poly(4-styrenesulfonate) results in wrapping
      of the nanotube, while complexation with an electron-accepting oxoanion such as
      anthraquinone carboxylate allows photoinduced electron transfer from the
      graphitic wall to the bound guest molecules.

PMID- 17227041
TI  - HPLC separation and NMR structural elucidation of sn-1,2-, 2,3-, and 1,3
      diacylglycerols from olive oil as naphthylethylurethane derivatives.
AB  - In this study, sn-1,2-, sn-2,3-, and sn-1,3-diacylglycerols were isolated from
      olive oil, and their urethane derivatives (urethanes) were prepared. Normal-phase
      high-performance liquid chromatography (NP-HPLC) separation of the urethane
      isomers was performed and the separate classes were studied by nuclear magnetic
      resonance (NMR). The use of 1H NMR and homo- and heteronuclear 2D techniques
      provided a great amount of information in a very short time, particularly when a
      high-field NMR instrument (700 MHz) was used. Particularly diagnostic for this
      kind of compound was the glyceridic moiety that presents typical chemical shifts
      both for carbon and hydrogen. These studies show the usefulness of NMR
      spectroscopy to recognize clearly the sn-1,3- and, moreover, sn-1,2- with respect
      to sn-2,3-diacylglycerols, although very minor differences occur between them.

PMID- 17227042
TI  - Improved detection of sugar addition to maple syrup using malic acid as internal
      standard and in 13C isotope ratio mass spectrometry (IRMS).
AB  - Stable carbon isotope ratio mass spectrometry (delta13C IRMS) was used to detect
      maple syrup adulteration by exogenous sugar addition (beet and cane sugar). Malic
      acid present in maple syrup is proposed as an isotopic internal standard to
      improve actual adulteration detection levels. A lead precipitation method has
      been modified to isolate quantitatively malic acid from maple syrup using
      preparative reversed-phase liquid chromatography. The stable carbon isotopic
      ratio of malic acid isolated from this procedure shows an excellent accuracy and
      repeatability of 0.01 and 0.1 per thousand respectively, confirming that the
      modified lead precipitation method is an isotopic fractionation-free process. A
      new approach is proposed to detect adulteration based on the correlation existing
      between the delta13Cmalic acid and the delta13Csugars-delta13Cmalic acid (r =
      0.704). This technique has been tested on a set of 56 authentic maple syrup
      samples. Additionally, authentic samples were spiked with exogeneous sugars. The
      mean theoretical detection level was statistically lowered using this technique
      in comparison with the usual two-standard deviation approach, especially when
      maple syrup is adulterated with beet sugar : 24 +/- 12% of adulteration detection
      versus 48 +/- 20% (t-test, p = 7.3 x 10-15). The method was also applied to
      published data for pineapple juices and honey with the same improvement.

PMID- 17227043
TI  - Solid-phase extraction combined with high-performance liquid chromatography
      atmospheric pressure chemical ionization-mass spectrometry analysis of pesticides
      in water: method performance and application in a reconnaissance survey of
      residues in drinking water in Greater Cairo, Egypt.
AB  - Monitoring of water resources for pesticide residues is often needed to ensure
      that pesticide use does not adversely impact the quality of public water supplies
      or the environment. In many rural areas and throughout much of the developing
      world, monitoring is often constrained by lack of testing facilities; thus,
      collection of samples and shipment to centralized laboratories for analysis is
      required. The portability, ease of use, and potential to enhance analyte
      stability make solid-phase extraction (SPE) an attractive technique for handling
      water samples prior to their shipment. We describe performance of an SPE method
      targeting a structurally diverse mixture of 25 current-use pesticides and two
      common degradates in samples of raw and filtered drinking water collected in
      Greater Cairo, Egypt. SPE was completed in a field laboratory in Egypt, and
      cartridges were shipped to the United States for elution and high-performance
      liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry
      analysis. Quantitative and reproducible recovery of 23 of 27 compounds (average =
      96%; percent relative standard deviation = 21%) from matrix spikes (1 microg L-1
      per component) prepared in the field and from deionized water fortified similarly
      in the analytical laboratory was obtained. Concurrent analysis of unspiked
      samples identified four parent compounds and one degradate in drinking water
      samples. No significant differences were observed between raw and filtered
      samples. Residue levels in all cases were below drinking water and "harm to
      aquatic-life" thresholds, indicating that human and ecological risks of pesticide
      contamination were relatively small; however, the study was limited in scale and
      scope. Further monitoring is needed to define spatial and temporal variation in
      residue concentrations. The study has demonstrated the feasibility of performing
      studies of this type using SPE to extract and preserve samples in the field. The
      approach should be broadly applicable in many settings.

PMID- 17227044
TI  - Preparation of anti-tetracycline antibodies and development of an indirect
      heterologous competitive enzyme-linked immunosorbent assay to detect residues of
      tetracycline in milk.
AB  - Tetracycline (TC) is a broad-spectrum antibiotic used increasingly in animal
      husbandry to treat diseases or to promote growth as feed additives. To avoid
      using labor-intensive instrumental methods to detect residues of TC in food and
      food products, a simple and convenient indirect heterologous competitive enzyme
      linked immunosorbent assay (ELISA) method for TC was developed using polyclonal
      antibody prepared in this study. Three new immunogens, TC-o-tolidine-bovine serum
      albumin (BSA), TC- 4-aminobenzoic acid-cationized BSA (cBSA), and TC-1,1'
      carbonyldiimidazole-cBSA, were synthesized in this research to develop anti-TC
      antibodies. All antibodies raised in rabbits and coating antigens synthesized
      were screened and characterized using homologous and heterologous ELISA formats
      to select the best combination. An optimized ELISA gave an IC50 value of 3.92
      mug/mL toward TC in PBS buffer. The specificity of the assay was studied by
      measuring cross-reactivity of the antibody with the structurally closely related
      compounds of chlortetracycline (112%) and oxytetracycline (<2%). The recovery
      rates from the TC-fortified raw milk samples were in the range of 74-116%, while
      the intra- and interassay coefficients of variation were <14.5 and <25.0,
      respectively.

PMID- 17227045
TI  - Internal standardization--atomic spectrometry and geographical pattern
      recognition techniques for the multielement analysis and classification of
      Catalonian red wines.
AB  - Major and minor (K, P, Ca, Mg, Na, Fe, Mn, Zn, and Sr) and trace (Ba, Ni, Pb, V,
      Co, Cd, and Sb) elements from wine samples from the Denomination of Origin (DO)
      Emporda-Costa Brava (Catalonia, Spain) were analyzed by inductively coupled
      plasma atomic emission spectrometry (ICP-AES) and mass spectrometry (ICP-MS)
      respectively. Previously, a comparison of different calibration methodologies and
      sample digestion treatments had been carried out using ANOVA statistical tool.
      The obtained results demonstrated that internal standardization provides reliable
      results with the advantage that no further manipulation of the sample is needed.
      A principal component analysis of the concentration data was performed to
      differentiate the samples of DO Emporda-Costa Brava from wine samples from other
      wine-producing regions in Spain (i.e., Penedes, Somontano, and Rioja). It was
      found that Sr and Ba contents discriminate the two DO groups. Moreover, a
      discriminant analysis function involving both variables distinguishes the two
      groups with a 100% classification rate. At the level of the leave-one-out cross
      validation, all of the Emporda-Costa Brava samples were well classified, whereas
      the other DOs presented two borderline misclassifications.

PMID- 17227046
TI  - Poly- and monoclonal antibody-based ELISAs for fipronil.
AB  - An enzyme-linked immunosorbent assay (ELISA) for fipronil was developed by using
      polyclonal antibodies (pABs) or monoclonal antibodies (mABs), and its suitability
      of the determination of this analyte in spiked water samples was studied. The
      pABs-based assay showed I50 = 17.95 ppb, I90 = 203.40 ppb, and I10 = 0.066 ppb,
      whereas the mABs-based assay showed I50 = 5.99 ppb, I90 = 485.40 ppb, and I10 =
      0.074 ppb. The recoveries of fipronil from tap water samples by pABs-based ELISA
      were 93.00-124.00% in the range of 0-500 ng/mL, and those obtained from the
      samples by mABs-based ELISA were 94.70-108.00%. Different types of water from
      pool, river, and sea were spiked at different levels (ranging form 0.1 to 10
      microg/L) and were assayed by the indirect ELISA with mABs. The recoveries of
      fipronil by this ELISA were in the range of 80-120%. The results demonstrate that
      this assay is suitable for the quantitative detection of fipronil at trace levels
      in water samples.

PMID- 17227047
TI  - Prediction of Japanese green tea ranking by gas chromatography/mass spectrometry
      based hydrophilic metabolite fingerprinting.
AB  - An innovative technique for green tea's quality determination was developed by
      means of metabolomics. Gas-chromatography coupled with time-of-flight mass
      spectrometry and multivariate data analysis was employed to evaluate the quality
      of green tea. Alteration of green tea varieties and manufacturing processes
      effects a variation in green tea metabolites, which leads to a classification of
      the green tea's grade. Therefore, metabolic fingerprinting of green tea samples
      of different qualities was studied. A set of ranked green tea samples from a
      Japanese commercial tea contest was analyzed with the aim of creating a reliable
      quality-prediction model. Several multivariate algorithms were performed. Among
      those, the partial least-squares projections to latent structures (PLS) analysis
      with the spectral filtering technique, orthogonal signal correction (OCS), was
      found to be the most practical approach. In addition, metabolites that play an
      important role in green tea's grade classification were identified.

PMID- 17227048
TI  - Colorimetric sensor array for soft drink analysis.
AB  - Fourteen commercial soft drinks have been analyzed using colorimetric sensor
      arrays made from a set of 25 chemically responsive dyes printed on a hydrophobic
      membrane. Digital imaging of the dye array before and after immersion provides a
      color change profile as a unique fingerprint for each specific analyte. The
      digital data library generated was analyzed with statistical and chemometric
      methods, including principal component analysis (PCA) and hierarchical clustering
      analysis (HCA). Facile identification of all of the soft drinks was readily
      achieved using comparison of the color change profiles or a PCA score plot. Using
      a HCA dendrogram, the misclassification rate was <2%, and even very similar sodas
      were easily differentiated. In addition, the monitoring of soft drinks as they
      degas or upon dilution also proved to be possible. This work demonstrates the
      potential of our colorimetric sensor array technology for quality
      assurance/control applications of sodas and perhaps other beverages as well.

PMID- 17227049
TI  - Structure-activity relationships of tea compounds against human cancer cells.
AB  - The content of the biologically active amino acid theanine in 15 commercial
      black, green, specialty, and herbal tea leaves was determined as the 2,4
      dinitrophenyltheanine derivative (DNP-theanine) by a validated HPLC method. To
      define relative anticarcinogenic potencies of tea compounds and teas, nine green
      tea catechins, three black tea theaflavins, and theanine as well as aqueous and
      80% ethanol/water extracts of the same tea leaves were evaluated for their
      ability to induce cell death in human cancer and normal cells using a tetrazolium
      microculture (MTT) assay. Compared to untreated controls, most catechins,
      theaflavins, theanine, and all tea extracts reduced the numbers of the following
      human cancer cell lines: breast (MCF-7), colon (HT-29), hepatoma (liver) (HepG2),
      and prostate (PC-3) as well as normal human liver cells (Chang). The growth of
      normal human lung (HEL299) cells was not inhibited. The destruction of cancer
      cells was also observed visually by reverse phase microscopy. Statistical
      analysis of the data showed that (a) the anticarcinogenic effects of tea
      compounds and of tea leaf extracts varied widely and were concentration dependent
      over the ranges from 50 to 400 microg/mL of tea compound and from 50 to 400
      microg/g of tea solids; (b) the different cancer cells varied in their
      susceptibilities to destruction; (c) 80% ethanol/water extracts with higher
      levels of flavonoids determined by HPLC were in most cases more active than the
      corresponding water extracts; and (d) flavonoid levels of the teas did not
      directly correlate with anticarcinogenic activities. The findings extend related
      observations on the anticarcinogenic potential of tea ingredients and suggest
      that consumers may benefit more by drinking both green and black teas.

PMID- 17227050
TI  - Quantitative analysis of anticancer 3-deoxyanthocyanidins in infected sorghum
      seedlings.
AB  - 3-Deoxyanthocyanidins are structurally related to the anthocyanin pigments, which
      are popular as health-promoting phytochemicals. Here, it is demonstrated that the
      3-deoxyanthocyanidins are more cytotoxic on human cancer cells than the 3
      hydroxylated anthocyanidin analogues. At 200 microM concentration, luteolinidin
      reduced the viability of HL-60 and HepG2 cells by 90 and 50%, respectively.
      Sorghum is a major source of 3-deoxyanthocyanidins, which are present as seed
      pigments and as phytoalexins responding to pathogen attack. On the basis of the
      collision-induced dissociation spectra of luteolinidin and apigeninidin, an LC
      MS/MS method, operating in multiple-reaction monitoring mode, was developed for
      the specific detection and accurate quantification of these compounds in complex
      mixtures, which may be difficult to analyze using absorbance measurements. The
      results demonstrated that inoculated sorghum seedlings could be utilized for
      convenient and large-scale production of 3-deoxyanthocyanidins. A quantity of
      almost 270 microg/g (fresh weight) of luteolinidin was produced 72 h after fungal
      inoculation of 1-week-old seedlings.

PMID- 17227051
TI  - Effects of a chitin-binding vicilin from Enterolobium contortisiliquum seeds on
      bean bruchid pests (Callosobruchus maculatus and Zabrotes subfasciatus) and
      phytopathogenic fungi (Fusarium solani and Colletrichum lindemuntianum).
AB  - Chitin-binding vicilin from Enterolobium contortisiliquum seeds was purified by
      ammonium sulfate followed by gel filtration on Sephacryl 300-SH and on Sephacryl
      200-SH. The vicilin, called EcV, is a dimeric glycoprotein composed of 1.03%
      carbohydrates and a Mr of 151 kDa, consisting of two subunits of Mr of 66.2 and
      63.8 kDa. The EcV homogeneity was confirmed in a PAGE where it was observed to be
      a unique acid protein band with slow mobility in this native gel. E.
      contortisiliquum vicilin (EcV) was tested for anti-insect activity against C.
      maculatus and Zabrotes subfasciatus larvae and for phytopathogenic fungi, F.
      solani and C. lindemuntianum. EcV was very effective against both bruchids,
      producing 50% mortality for Z. subfasciatus at an LD50 of 0.43% and affected 50%
      of the larvae mass with an ED50 of 0.65%. In artificial diets given to C.
      maculatus, 50% of the larvae mass was affected with an ED50 of 1.03%, and larva
      mortality was 50% at LD50 of 1.11%. EcV was not digested by midgut homogenates of
      C. maculatus and Z. Subfasciatus until 12 h of incubation, and at 24 h EcV was
      more resistant to Z. subfasciatus larval proteases. The binding to chitin present
      in larvae gut associated to low EcV digestibility could explain its lethal
      effects. EcV also exerted an inhibitory effect on the germination of F. solani at
      concentrations of 10 and 20 microg mL-1. The effect of EcV on fungi is possibly
      due to binding to chitin-containing structures of the fungal cell wall.

PMID- 17227052
TI  - Supplementation of test meals with fat-free phytosterol products can reduce
      cholesterol micellarization during simulated digestion and cholesterol
      accumulation by Caco-2 cells.
AB  - Phytosterols have been shown to reduce cholesterol absorption in humans.
      Supplementing phytosterols in fat-free formulations, however, has yielded
      controversial results. In the present study, we investigated the effect of
      supplementing test meals with different fat-free phytosterol products on
      cholesterol incorporation into mixed micelles during simulated digestion and
      accumulation of micellar cholesterol by Caco-2 cells: control orange juice (OJ),
      orange juice supplemented with either multivitamin/multimineral tablets (MVT),
      multivitamin/multimineral tablets containing phytosterols (MVT+P), and
      phytosterol powder (PP). These combinations were added to Ensure-based test meals
      and spiked with cholesterol of natural isotopic composition or 13C2-cholesterol
      to differentiate external from endogenous cholesterol. After simulated
      gastric/small intestinal digestion, micelle fractions were analyzed for
      cholesterol enzymatically (n = 6-20/product) and by high-performance liquid
      chromatography-tandem mass spectrometry (n = 12/product) and added to Caco-2
      cells to determine the accumulation of 13C2-cholesterol (n = 10-24/product). As
      compared to OJ, PP and MVT+P significantly decreased cholesterol micellarization
      (determined enzymatically) by 70 +/- 39 (mean +/- SD) and 70 +/- 39%,
      respectively (P < 0.001, Bonferroni). The stable isotope experiments revealed
      that both PP and MVT+P reduced cholesterol micellarization [by 25 +/- 12 (P =
      0.055) and 21 +/- 8% (P = 0.020), respectively, Fisher's protected LSD test] and
      Caco-2 cell accumulation (by 28 +/- 8 and 10 +/- 8%, respectively; P < 0.010,
      Bonferroni). OJ+P did not inhibit micellarization or accumulation of cholesterol
      by Caco-2 cells. This study shows that fat-free phytosterol-containing products
      can significantly inhibit cholesterol micellarization and Caco-2 cell
      bioaccessibility, albeit to different extents depending on individual
      formulations. This is most likely explained by inhibition of cholesterol
      micellarization.

PMID- 17227053
TI  - Absorption and excretion of luteolin and apigenin in rats after oral
      administration of Chrysanthemum morifolium extract.
AB  - Chrysanthemum morifolium extract (CME) has the protective effect on
      cardiovascular diseases. Luteolin and apigenin are two major bioactive components
      in vivo when CME is orally administrated to experimental animal. The present
      paper shows the study of the absorption and excretion of luteolin and apigenin in
      rats after a single oral dose of CME (200 mg/kg). The levels of luteolin and
      apigenin in plasma, urine, feces, and bile were measured by HPLC after
      deconjugation with hydrochloric acid or beta-glucuronidase/sulfatase. The results
      showed that the plasma concentrations of luteolin and apigenin reached the
      highest peak level at 1.1 and 3.9 h after dosing, respectively. The area under
      the concentration-time curves (AUC) for luteolin and apigenin were 23.03 and
      237.6 microg h mL-1, respectively. The total recovery of the dose was 37.9% (6.6%
      in urine; 31.3% in feces) for luteolin and 45.2% (16.6% in urine; 28.6% in feces)
      for apigenin. The cumulative luteolin and apigenin excreted in the bile was 2.05%
      and 6.34% of the dose, respectively. All of the results suggest apigenin may be
      absorbed more efficiently than luteolin in CME in rats, and both luteolin and
      apigenin have a slow elimination phase, with a quick absorption, so a possible
      accumulation of the two flavonoids in the body can be hypothesized.

PMID- 17227054
TI  - Effect of barley coffee on the adhesive properties of oral streptococci.
AB  - Some beverages and foods protect tooth surfaces against Streptococcus mutans
      colonization. Adhesion of S. mutans is a crucial step in the initiation and
      development of dental caries. In this study, we showed that barley coffee (BC), a
      beverage made from roasted barley, interferes with S. mutans adsorption to
      hydroxyapatite (HA), and we identified its antiadhesive components. The effects
      of sublethal concentrations (sub-MICs) of BC on the adhesion of S. mutans to
      saliva-coated HA beads were assessed using three experimental approaches: (A)
      Beads were pretreated with BC before adding bacteria, (B) BC and bacteria were
      added to the beads simultaneously, and (C) streptococci grown in the presence of
      sub-MICs of BC were added to the beads. All treatments induced variable but
      significant inhibition of S. mutans sucrose-dependent and -independent adherence
      to HA. Similar results were obtained with other oral streptococci. BC components
      were fractioned by dialysis and gel filtration chromatography; the <1000 Da
      molecular mass (MM) fraction, which contains polyphenols, zinc, and fluoride
      ions, and the >1000 kDa MM fraction, which consists of a potent brown
      antioxidant, melanoidin, both displayed antiadhesive properties. High-MM
      melanoidin was not detected in unroasted barley, indicating that it forms during
      the roasting process. Results suggest that BC consumption may influence the
      colonization of tooth surfaces by cariogenic bacteria.

PMID- 17227055
TI  - Comparison of extraction methods for the quantification of selected
      phytochemicals in peanuts (Arachis hypogaea).
AB  - Peanuts have been reported to contain bioactive phytochemicals, particularly
      isoflavones (genistein, daidzein, and biochanin A) and trans-resveratrol.
      Currently, limited data are available regarding the levels of these bioactive
      compounds in peanuts with variations in reported levels. The purpose of this
      study was to compare four methods of extraction [stirring, sonication, Soxtec,
      and microwave-assisted sonication (MAS)] for runner peanuts. Quantification of
      the selected compounds was conducted by reverse-phase high-performance liquid
      chromatography (RP-HPLC). The results showed that the MAS and Soxtec methods
      extracted significantly higher amounts of the phytochemicals. Also, the defatted
      peanuts gave significantly higher amounts of the phytochemicals compared to the
      nondefatted peanuts. The high levels of the isoflavones may be attributed to heat
      induced conversion of conjugate glycosides to aglycons. The MAS and Soxtec
      methods may be used for total isoflavone content quantitation, while sonication
      or stirring may be the method of choice for quantitation of isoflavone
      composition (aglycons and glycoside conjugates) in peanuts.

PMID- 17227056
TI  - High-amylose corn exhibits better antioxidant activity than typical and waxy
      genotypes.
AB  - The consumption of fruits, vegetables, and whole grains rich in antioxidative
      phytochemicals is associated with a reduced risk of chronic diseases such as
      cancer, coronary heart disease, diabetes, Alzheimer's disease, cataract, and aged
      related functional decline. For example, phenolic acids are among the main
      antioxidative phytochemicals in grains that have been shown to be beneficial to
      human health. Corn (Zea mays L.) is a major staple food in several parts of the
      world; thus, the antioxidant activity of several corn types was evaluated. The
      2,2-Diphenyl-1-picryhydrazyl free radical (DPPH*) scavenging activity, total
      phenolic content (TPC), antioxidant capacity of lipid-soluble substances (ACL),
      oxygen radical absorbance capacity (ORAC), and phenolic acid compositions of
      typical and mutant genotypes (typical-1, waxy, typical-2, and high-amylose) were
      investigated. The DPPH* scavenging activity at 60 min was 34.39-44.51% in
      methanol extracts and 60.41-67.26% in HCl/methanol (1/99, v/v) extracts of corn.
      The DPPH* scavenging activity of alkaline hydrolysates of corn ranged from 48.63
      to 64.85%. The TPC ranged from 0.67 to 1.02 g and from 0.91 to 2.15 g of ferulic
      acid equiv/kg of corn in methanol and HCl/methanol extracts, respectively. The
      TPC of alkaline hydrolysates ranged from 2.74 to 6.27 g of ferulic acid equiv/kg
      of corn. The ACL values were 0.41-0.80 and 0.84-1.59 g of Trolox equiv/kg of corn
      in methanol and HCl/methanol extracts, respectively. The ORAC values were 10.57
      12.47 and 18.76-24.92 g of Trolox equiv/kg of corn in methanol and HCl/methanol
      extracts, respectively. ORAC values of alkaline hydrolysates ranged from 42.85 to
      68.31 g of Trolox equiv/kg of corn. The composition of phenolic acids in alkaline
      hydrolysates of corn was p-hydroxybenzoic acid (5.08-10.6 mg/kg), vanillic acid
      (3.25-14.71 mg/kg), caffeic acid (2.32-25.73 mg/kg), syringic acid (12.37-24.48
      mg/kg), p-coumaric acid (97.87-211.03 mg/kg), ferulic acid (1552.48-2969.10
      mg/kg), and o-coumaric acid (126.53-575.87 mg/kg). Levels of DPPH* scavenging
      activity, TPC, ACL, and ORAC in HCl/methanol extracts were obviously higher than
      those present in methanol extracts. There was no significant loss of antioxidant
      capacity when corn was dried at relatively high temperatures (65 and 93 degrees
      C) postharvest as compared to drying at ambient temperatures (27 degrees C).
      Alkaline hydrolysates showed very high TPC, ACL, and ORAC values when compared to
      methanol and HCl/methanol extracts. High-amylose corn had a better antioxidant
      capacity than did typical (nonmutant) corn genotypes.

PMID- 17227057
TI  - Food components inhibiting recombinant human histidine decarboxylase activity.
AB  - Histidine decarboxylase (HDC) catalyzes histamine formation from histidine.
      Histamine is a bioactive amine acting as a neurotransmitter as well as a chemical
      mediator. Phenolic food components have been tested for their ability to inhibit
      recombinant human HDC. Epicatechin gallate (ECG) was found to be a potent
      inhibitor as it inhibited HDC activity in a competitive manner with Ki = 10 muM
      against l-histidine. Epigallocatechin gallate (EGCG) showed time-dependent
      inhibition which disappeared under anaerobic conditions. It is probable that time
      dependent inhibition could be due to the result of autoxidation of EGCG. The
      initial burst observed for EGCG suggests that EGCG itself is involved in HDC
      inhibition as observed for ECG. Our present results have shown that the tested
      food components can inhibit HDC activity. This inhibition likely affects
      histamine biosynthesis and possibly leads to controlling the biological action
      induced by histamine. Therefore, those food components exhibiting HDC inhibitory
      activity might be potentially useful in controlling histamine-induced biological
      actions.

PMID- 17227058
TI  - Detection of land animal remains in fish meals by the polymerase chain reaction
      restriction fragment length polymorphism technique.
AB  - In the present study a technique was developed with the aim of guaranteeing the
      composition and security of fish meals, since it allows verification of whether
      these meals contain land animal remains. The method is based on polymerase chain
      reaction (PCR) and length polymorphism, followed by a restriction fragment length
      polymorphism (RFLP). Specific primers for every species were designed and
      calibrated, generating exclusively a PCR product with a specific size when DNA
      for each species was present in the sample. This technique allows the detection
      of land animal remains in fish meals, specifically cow, chicken, pig, horse,
      sheep, and goat. The identity of the PCR products can be confirmed by RFLP
      analysis using only one restriction enzyme. The selected restrictase generated
      one characteristic restriction profile for every species included in this study.
      The detection limit of this method was calculated by using mixtures of fish meals
      in different proportions and meal that exclusively contained remains of one of
      these land species studied. The analytical strategy herein proposed was applied
      to fish and meat meals, giving good results, both in the analyzed standards and
      in commercial samples.

PMID- 17227059
TI  - Influence of winemaking practices on the concentration of rare earth elements in
      white wines studied by inductively coupled plasma mass spectrometry.
AB  - Influence of clarification, filtration, and storage on the concentration of rare
      earth elements (REEs) was studied in white wines by inductively coupled plasma
      mass spectrometry (ICP-MS). Smooth and parallel chondrite-normalized (CN) plots
      were obtained for wines which have never been in contact with fining agents.
      Clarification and filtration generally used in white wine production were
      simulated in the laboratory using nontreated reference wines, and CN plots were
      compared before and after treatments. Clarification by bentonites yields an
      overall increase in REE concentrations resulting in substantially parallel CN
      curves well above the plots of the corresponding nontreated wines. Filtration
      using silicate (SiO2), on the other hand, changes the CN profile in a nonparallel
      manner due to a higher release of La, Ce, Pr, Nd, and Gd, more than other
      elements studied. Filtration with cellulose powder causes a small increase in the
      concentration of light REEs, while the concentrations of other elements remain
      basically unchanged. Storage conditions could also affect the REE pattern of
      wine. We found that the influence of glass is greater than that of stainless
      steel and wood. In addition, we report that commercially available finished white
      wines from the same region show highly different REE patterns depending on the
      winemaking practices employed.

PMID- 17227060
TI  - Formation of amyloid-like fibrils by ovalbumin and related proteins under
      conditions relevant to food processing.
AB  - Protein aggregation is important in food processing, and this work investigated
      the aggregation of food proteins as a source of amyloid fibrils for use in
      bionanotechnology. Both purified and crude mixtures of albumin proteins were
      denatured by heat, which caused aggregation to occur. Protein denaturation was
      measured by using circular dichroism spectrometry and by following thioflavin T
      fluorescence, which is widely used as a diagnostic test for amyloid formation.
      There was a good correlation between the increase in thioflavin T fluorescence
      and loss of helical structure as the temperature was increased. Formation of
      thioflavin T fluorescence was dependent on temperature, but less dependent on
      salt and protein concentration. X-ray fiber diffraction patterns of denatured
      bovine serum albumin suggested that the protein had a similar cross-beta
      structure to that of amyloid fibrils. These results are consistent with the
      aggregates seen during food processing, being amyloid-like in nature.

PMID- 17227061
TI  - Photoprotection of vitamins in skimmed milk by an aqueous soluble lycopene-gum
      Arabic microcapsule.
AB  - Riboflavin (Rf)-mediated photosensitized degradation of vitamins A and D3 in
      skimmed milk under illumination with a white fluorescence lamp was studied by
      using the HPLC technique. The photosensitized degradation of both vitamins
      followed first-order kinetics, and the temperature effect on the observed
      photodegradation rate constant allowed the determination of the activation energy
      Ea as being 4 and 16 kcal/mol for vitamins A and D3, respectively. The addition
      of lycopene microencapsulated by spray-drying with a gum arabic-sucrose (8:2)
      mixture (MIC) produced a reduction of ca. 45% in the photosensitized degradation
      rate of both vitamins. Front-face fluorescence experiments showed the same
      photoprotection factor in the degradation of Rf itself, indicating that the
      photodegradation mechanism involved Rf-mediated reactive species, such as the
      excited triplet state of Rf, 3Rf*, and/or singlet molecular oxygen, 1O2. The
      interaction of both 3Rf* and 1O2 with MIC was evaluated in aqueous solutions by
      using laser-induced time-resolved absorption or emission spectroscopy, and the
      contribution of an inner-filter effect in the presence of MIC in skimmed milk was
      evaluated by diffuse reflectance spectroscopy. The main operating mechanism of
      photoprotection is due to the deactivation of 3Rf* by the proteic component of
      gum arabic; thus, gum arabic based microcapsules could be used to improve the
      photostability of milk during its storage and/or processing under light.

PMID- 17227062
TI  - Effect of heat treatment on the phenolic compounds and antioxidant capacity of
      citrus peel extract.
AB  - This paper reports the effects of heat treatment on huyou (Citrus paradisi
      Changshanhuyou) peel in terms of phenolic compounds and antioxidant capacity.
      High-performance liquid chromatography (HPLC) coupled with a photodiode array
      (PDA) detector was used in this study for the analysis of phenolic acids (divided
      into four fractions: free, ester, glycoside, and ester-bound) and flavanone
      glycosides (FGs) in huyou peel (HP) before and after heat treatment. The results
      showed that after heat treatment, the free fraction of phenolic acids increased,
      whereas ester, glycoside, and ester-bound fractions decreased and the content of
      total FGs declined (P < 0.05). Furthermore, the antioxidant activity of methanol
      extract of HP increased (P < 0.05), which was evaluated by total phenolics
      contents (TPC) assay, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS*+)
      method, and ferric reducing antioxidant power (FRAP) assay. The correlation
      coefficients among TPC, ABTS, FRAP assay, and total cinnamics and benzoics (TCB)
      in the free fraction were significantly high (P < 0.05), which meant that the
      increase of total antioxidant capacity (TAC) of HP extract was due at least in
      part to the increase of TCB in free fraction. In addition, FGs may be destroyed
      when heated at higher temperature for a long time (for example, 120 degrees C for
      90 min or 150 degrees C for 30 min). Therefore, it is suggested that a proper and
      reasonable heat treatment could be used to enhance the antioxidant capacity of
      citrus peel.

PMID- 17227063
TI  - Cooking behavior of rice in relation to kernel physicochemical and structural
      properties.
AB  - A set of 27 rice varieties were evaluated for their morphological grain
      characteristics (length, width, thickness, thousand kernel weight, TKW), chemical
      composition (amylose, protein, and ash content) and starch properties
      (gelatinization temperature and enthalpy, amylose-lipid complex). In addition,
      cell walls were characterized by the arabinoxylan and beta-glucan contents. A
      rapid method for determining optimum rice cooking time was developed based on the
      swelling ratio; a fixed value of 2.55 gave a gelatinization level of 95% assessed
      by differential scanning calorimetry and translucence testing. Optimum cooking
      time appears positively correlated with kernel thickness and TKW but also with
      ash content. Confocal laser and scanning electron microscope observation of
      uncooked rice grains revealed different structural features (cell size) and
      fracture behavior: for some cultivars, the fracture showed ruptured cells,
      whereas for others most cells were intact. These structural differences, which
      may be linked to pectin content, could partly explain rice kernel cooking
      behavior.

PMID- 17227064
TI  - Determination of the geographic origin of onions between three main production
      areas in Japan and other countries by mineral composition.
AB  - Onions (Allium cepa L.) are produced in many countries and are one of the most
      popular vegetables in the world, thus leading to an enormous amount of
      international trade. It is currently important that a scientific technique be
      developed for determining geographic origin as a means to detect fraudulent
      labeling. We have therefore developed a technique based on mineral analysis and
      linear discriminant analysis (LDA). The onion samples used in this study were
      from Hokkaido, Hyogo, and Saga, which are the primary onion-growing areas in
      Japan, and those from countries that export onions to Japan (China, the United
      States, New Zealand, Thailand, Australia, and Chile). Of 309 samples, 108 were
      from Hokkaido, 52 were from Saga, 77 were from Hyogo, and 72 were from abroad.
      Fourteen elements (Na, Mg, P, Mn, Co, Ni, Cu, Zn, Rb, Sr, Mo, Cd, Cs, and Ba) in
      the samples were determined by frame atomic adsorption spectrometry, inductively
      coupled plasma optical emission spectrometry, and inductively coupled plasma mass
      spectrometry. The models established by LDA were used to discriminate the
      geographic origin between Hokkaido and abroad, Hyogo and abroad, and Saga and
      abroad. Ten-fold cross-validations were conducted using these models. The
      discrimination accuracies obtained by cross-validation between Hokkaido and
      abroad were 100 and 86%, respectively. Those between Hyogo and abroad were 100
      and 90%, respectively. Those between Saga and abroad were 98 and 90%,
      respectively. In addition, it was demonstrated that the fingerprint of an element
      pattern from a specific production area, which a crop receives, did not easily
      change by the variations of fertilization, crop year, variety, soil type, and
      production year if appropriate elements were chosen.

PMID- 17227065
TI  - Enrichment of tocopherols and phytosterols in canola oil during seed germination.
AB  - The effect of canola (Brassica napus L.) seed germination under illuminated and
      dark environments on the total concentration and the composition of tocopherols
      and phytosterols in seedlings and extracted oil were investigated. During the
      first 10 days of germination, a decrease in gamma-tocopherol was offset by an
      increase in alpha-tocopherol, indicating the interconversion of these isomers.
      From day 10 to day 20 under illumination, there was a net increase in alpha
      tocopherol and total tocopherols suggesting the synthesis of new tocopherols,
      whereas there was no net increase in tocopherols in dark. Tocopherols were mainly
      concentrated in the leafy seedling tops rather than in the non-photosynthesizing
      bottoms, whereas phytosterols were equally distributed across both sections. The
      total tocopherol content of oil extracted from 20-day-old seedlings was 4.3- to
      6.5-fold higher than that of intact seeds. On a dry seedling basis, the content
      and composition of phytosterols did not change significantly (p > 0.05) over the
      sprouting period, but the concentration of total phytosterols in the oil fraction
      increased 4.2- to 5.2-fold. The concentration of these valuable phytochemicals in
      the oil fraction is largely due to the depletion of oil reserves during
      germination, as well as the de novo synthesis of new alpha-tocopherol stimulated
      by the presence of light. Germination may represent a viable means to naturally
      concentrate these high-value constituents in canola oil, offering improvements in
      oil quality based on the nutritional value and oxidative protection offered by
      tocopherols and the health benefits provided by both tocopherols and
      phytosterols.

PMID- 17227066
TI  - Amino acid composition and antioxidant capacity of Spanish honeys.
AB  - The amino acid composition of 53 honey samples from Spain, consisting of 39
      floral, 5 honeydew, and 9 blend honeys, has been determined. Physicochemical
      characteristics, polyphenolic content, amino acid composition, and estimation of
      the radical scavenging capacity against the stable free radical DPPH of the honey
      samples were analyzed. The resulting data have been statistically evaluated. The
      results showed that pH, acidity, net absorbance, electrical conductivity, and
      total polyphenolic contents of the honeys showed a strong correlation with the
      radical scavenging capacity. The correlation between the radical scavenging
      capacity of honey and amino acid contents was high with 18 of the 20 amino acids
      detected, with correlation values higher than those obtained for polyphenolic
      content. These results suggest that the amino acid composition of honey is an
      indicator of the sample's scavenging capacity.

PMID- 17227067
TI  - Andean potato cultivars (Solanum tuberosum L.) as a source of antioxidant and
      mineral micronutrients.
AB  - Potato tubers were evaluated as a source of antioxidants and minerals for the
      human diet. A genetically diverse sample of Solanum tuberosum L. cultivars native
      to the Andes of South America was obtained from a collection of nearly 1000
      genotypes using microsatellite markers. This size-manageable collection of 74
      landraces, representing at best the genetic diversity among potato germplasm, was
      analyzed for iron, zinc, calcium, total phenolic, total carotenoid, and total
      vitamin C contents. The hydrophilic antioxidant capacity of each genotype was
      also measured using the oxygen radical absorbance capacity (ORAC) assay. The iron
      content ranged from 29.87 to 157.96 microg g-1 of dry weight (DW), the zinc
      content from 12.6 to 28.83 microg g-1 of DW, and the calcium content from 271.09
      to 1092.93 microg g-1 of DW. Total phenolic content varied between 1.12 and 12.37
      mg of gallic acid equiv g-1 of DW, total carotenoid content between 2.83 and
      36.21 microg g-1 of DW, and total vitamin C content between 217.70 and 689.47
      microg g-1 of DW. The range of hydrophilic ORAC values was 28.25-250.67 micromol
      of Trolox equiv g-1 of DW. The hydrophilic antioxidant capacity and the total
      phenolic content were highly and positively correlated (r = 0.91). A strong
      relationship between iron and calcium contents was also found (r = 0.67).
      Principal component analysis on the studied nutritional contents of the core
      collection revealed that most potato genotypes were balanced in terms of
      antioxidant and mineral contents, but some of them could be distinguished by
      their high level in distinct micronutrients. Correlations between the
      micronutrient contents observed in the sample and the genetic distances assessed
      by microsatellites were weakly significant. However, this study demonstrated the
      wide variability of health-promoting micronutrient levels within the native
      potato germplasm as well as the significant contribution that distinct potato
      tubers may impart to the intake in dietary antioxidants, zinc, and iron.

PMID- 17227068
TI  - Effects of season and postharvest storage on the carotenoid content of Solanum
      phureja potato tubers.
AB  - The total carotenoid content was determined of tubers from 38 Solanum phureja
      lines grown in field plots over 3 years. The results indicated a significant
      difference between years, but the ranking was similar from year to year and the
      interaction between season and variety was small. Postharvest storage
      significantly reduced the carotenoid content of the tubers, and reducing the
      storage temperature further lowered the carotenoid content. Examination of the
      individual carotenoids revealed that lutein was the most stable and least likely
      to be reduced, while the levels of the carotenoids derived from beta-carotene
      were significantly reduced during storage at either temperature. Exposure of the
      tubers to either mercury or sodium lights resulted in a significant increase in
      total carotenoid content, concomitant with elevated chlorophyll. Although both
      types of radiation produced a broadly similar increase in total carotenoid
      contents, differential effects on the individual carotenoid profile of the light
      induced carotenoids were observed.

PMID- 17227069
TI  - Survey of dioxin-like compounds in dairy feeds in the United States.
AB  - The United States Environmental Protection Agency (USEPA) has completed a survey
      of dioxin-like compounds (including 17 dioxin and furan (CDD/F) congeners and 12
      coplanar polychlorinated biphenyl (PCBs) congeners) in dairy feeds from 10 dairy
      research facilities around the United States, sampling the overall mixtures and
      the major and minor feed components. Low levels of dioxin were found in all feed
      mixtures with an average concentration of 0.05 pg/g (ppt) toxic equivalent (TEQ)
      dry weight. This is lower than previously found in dairy feeds by about a factor
      of 4. While it is possible that generally lower levels of dioxins in the
      environment in recent years may explain this result, examinations of the data
      suggest that the oven drying used to prepare the wet feed samples could have
      resulted in a loss of dioxins from the feed materials. The percentage of the
      total TEQ due to CDD/Fs was about four times that of PCBs. Leafy vegetations in
      the feed (the silages and the hays) had concentrations about twice as high as
      nonleafy, protected vegetation of the feeds (the ground or meal corn, cottonseed,
      and others). Minor components did not significantly influence the final feed
      mixture concentration of dioxin TEQ. However, in one of the feed mixtures, a
      minor component with a high concentration of 38.5 ppt TEQ effectively doubled the
      concentration of the overall feed mixture.

PMID- 17227070
TI  - Adaptation of the biobed composition for chlorpyrifos degradation to Southern
      Europe conditions.
AB  - Biobeds developed in Sweden bind and degrade pesticides from point sources. The
      objective of this work was to adapt the biobed to Italian operating conditions,
      for example, to identify organic materials as effective as those in the original
      Swedish composition. The capacity of urban and garden composts alone or mixed
      with citrus peel or straw to degrade chlorpyrifos and its metabolite TCP was
      compared to the typical Swedish biomix consisting of straw, peat, and soil. A
      tendency for higher 14C-chlorpyrifos mineralization and lower TCP levels was
      observed in the biomixes with garden compost alone or amended with straw. In a
      second trial, a high correlation of lower TCP with increasing levels of straw in
      typical Swedish biomixes was observed. Straw stimulates production of lignin
      degrading enzymes such as manganese peroxidase (MnP), and further trials with
      pure MnP showed that this enzyme degrades TCP. Materials with an active lignin
      degrading microflora are a prerequisite for effective dissipation of chlorpyrifos
      and non-accumulation of TCP. Thus, lignocellulosic materials as straw and garden
      composts should be present in biomixes to be used under Italian conditions.

PMID- 17227071
TI  - Potential use of biodegradable chelate N-(1,2-dicarboxyethyl)-D,L-aspartic
      acid/Fe3+ as an Fe fertilizer.
AB  - In the past several years, concern about the environmental fate of recalcitrant
      synthetic ligands (e.g., EDTA) has increased. The used of new biodegradable
      chelating agents such as imidodisuccinic acid (IDHA) has been proposed as an
      alternative. However, its application as an iron ligand to correct iron chlorosis
      in agriculture has not yet been studied. Then the objective of this work is to
      determine the fertilizer capacity of IDHA/Fe3+ using interaction assays with
      soils and soil materials and evaluating Fe nutrition of efficient and susceptible
      plants. Interaction of IDHA/Fe3+ with soil materials produces a reduction of the
      amount of soluble Fe. This is in good agreement with studies on the stability of
      the IDHA/Fe3+ chelate. In general, plant response to IDHA/Fe3+ in hydroponics is
      acceptable and better than that to EDTA/Fe3+. This good behavior seems to be
      related to the lower coordination of the iron in IDHA/Fe3+ with respect to
      EDTA/Fe3+.

PMID- 17227072
TI  - Size distribution, complexing capacity, and stability of phosphate-metal-humic
      complexes.
AB  - Size distribution, maximum complexing ability, and stability constants for
      phosphate-metal-humic (PO43--M-HA) complexes involving two trivalent (Fe and Al)
      and five divalent metal (M) bridges (Zn, Cu, Mn, Ca, and Mg) were investigated at
      the pH values 4, 6, and 8. Results highlighted the existing competition between
      metal-humic acid (M-HA) aggregation and the formation of PO43--M-HA complexes.
      However, the fact that only a very low fraction of complexed metal is involved in
      PO43- fixation seems to be related to the existence of specific electronic and/or
      steric requirements in the binding site in the metal-humic complex. The
      importance of the ionic form of phosphate (H2PO4- or HPO42-) and the involvement
      of phenolic and especially carboxylic groups in the phosphate binding are
      discussed. Finally, the order of stability obtained for PO43--M-HA complexes was
      similar to that of M-HA complexes. This result suggests that PO43--M-HA might
      play a significant role in the dynamics of phosphorus in certain soil types.

PMID- 17227073
TI  - Influence of epicatechin reactions on the mechanisms of Maillard product
      formation in low moisture model systems.
AB  - The influence of the polyphenolic compound epicatechin on Maillard chemistry was
      investigated under simulated roast conditions (10% moisture at 220 degrees C for
      10 min). Quantitative gas chromatography (GC) analysis indicated that the
      addition of epicatechin to glucose or fructose/glycine model systems
      significantly reduced the generation of hydroxyacetone, 2-methylpyrazine, 2,3,5
      trimethylpyrazine, furfural, 2-acetylfuran, 5-methylfurfural, 2(5H)-furanone, 2
      acetylpyrrole, and furfuryl alcohol. These analytes were reported to be primarily
      generated from intact C2, C3, C4, C5, and C6 sugar fragments based on gas
      chromatography/mass spectrometry quantitative isotopomeric analysis of a 1:1
      13C6:12C6 hexose sugar/glycine model system. Liquid chromatography/mass
      spectrometry qualitative isotopomeric analysis of a 1:1 13C6:12C6 hexose
      sugar/glycine/epicatechin model systems confirmed epicatechin reacted with
      Maillard reactants in the model systems; two main reaction products were
      reported, epicatechin-C5 and -C6 sugar fragment adducts. In addition, LC/MS
      analysis of a model system consisting of only 3-deoxy-2-hexosulose and
      epicatechin identified 3-deoxy-2-hexosulose as a precursor of the epicatechin-C5
      and -C6 sugar fragment adducts reaction products. These results imply that
      epicatechin quenched 3-deoxy-2-hexosulose (a key source C6 to C1 sugar fragments)
      and consequently inhibited Maillard product formation.

PMID- 17227074
TI  - Model studies on the influence of matrix type and storage environment on the
      stability of a model aroma mixture during storage.
AB  - The objective of this study was to investigate the effect of oxygen in the
      storage atmosphere on the degradation of model compounds when present in water or
      a medium chain triglyceride (MCT) matrix. A model aroma compound mixture was
      prepared in oil (MCT) or water, and it was then stored under either an ambient
      air or argon atmosphere containing respectively ca. 20% and <0.5% residual
      oxygen. Samples were analyzed by SPME-GC/MS to determine the relative stability
      over time of different classes of aroma compounds. The low-oxygen atmosphere
      appeared to have a significant protective effect on sulfur compounds, aldehydes,
      and ketones in oil but a detrimental influence on pyrroles. Data showed little
      influence of the atmosphere for these compounds in water. In addition, the type
      of matrix had a significant effect (P < 0.05) on the stability of aldehydic,
      ester, and pyrrole compounds. These compounds were more stable in MCT than in
      water.

PMID- 17227075
TI  - Selected odor compounds in soymilk as affected by chemical composition and
      lipoxygenases in five soybean materials.
AB  - Protein, fat content, and beany odor affect consumers' choice of soy foods. Our
      objective was to characterize protein, lipid, and lipoxygenase activities and
      fatty acid compositions in food soybeans and to determine how chemical
      composition and enzyme activities related to the generation of beany odor
      components, including hexanal, hexanol, trans-2-nonenal, 1-octen-3-ol, and trans
      2,trans-4-decadienal in soymilk. Protein, lipid, and fatty acid compositions and
      lipoxygenase activities of five soybean materials, including Proto, IA2032, IA
      2064, IA3017, and L-Star varieties, were analyzed. Soymilk was prepared by a
      traditional method involving soaking, grinding, and cooking processes. Selected
      odor compounds in raw and cooked soymilk were analyzed by solid-phase
      microextraction and gas chromatography. Results showed that soybeans differed in
      crude protein and lipid content, lipoxygenase activities, and fatty acid
      compositions. L-Star had the highest and Proto the lowest lipid content among the
      five soybean cultivars. Protein content, lipoxygenases, and linoleic acid were
      positively correlated with beany odor content in soymilk made from the selected
      soybean materials. After boiling for 20 min, the soymilk made from L-Star and
      IA2032 retained the lowest odor profiles among the soymilk products made from the
      five selected materials.

PMID- 17227076
TI  - Transglutaminase polymerization of peanut proteins.
AB  - Transglutaminase promotes protein cross-linking reactions through an acyl
      transferase mechanism involving protein-bound glutaminyl residues and primary
      amines including the epsilon-amino group of lysine residues in soy, myosin,
      gluten, oat globulin, casein, and whey. Herein, we present a first report of
      exogenous transglutaminase catalysis of several peanut protein fractions,
      including purified Ara h 1. In most cases, SDS-PAGE banding patterns revealed the
      formation of high molecular weight polymers while catalysis of Ara h 1 resulted
      in distinct dimer formation. Cross-linking effects were accomplished in the
      presence and absence of the reducing reagent, dithiothreitol. Ortho
      phthaldialdehyde assays, used to quantify the degree of polymerization, indicated
      approximately 21% and approximately 30% coupling over a similar time interval,
      using either cold hexane extracted peanut protein fractions or lightly roasted
      flour dispersions, respectively. Rheological measurements established that
      transglutaminase-modified peanut extracts exhibited lowered viscosity readings
      compared to nontreated dispersions. Peanut protein polymers and glycoprotein
      conjugates, created by covalent linkage between protein substrates and
      monosaccharide amino sugars, exhibited similar IgE binding activity, compared to
      control solutions. These results suggested that potential allergic responses were
      not enhanced after enzymatic modification. Ultimately, these approaches may
      provide novel peanut-based food ingredients with unique functional
      characteristics for expanded applications within the world marketplace.

PMID- 17227077
TI  - Effect of alkaline deamidation on the structure, surface hydrophobicity, and
      emulsifying properties of the Z19 alpha-zein.
AB  - Different deamidation conditions for the Z19 alpha-zein were studied in order to
      find the best conditions for the development of the emulsifying properties.
      Alkaline deamidation was chosen, and the effects on the peptide bond cleavage,
      secondary structure, emulsifying properties, and surface hydrophobicity were
      studied. The Z19 alpha-zein was deamidated by using 0.5 N NaOH containing 70%
      ethanol at 70 degrees C for 12 h. A deamidation degree (DD) of 60.6 +/- 0.5%, and
      a degree of hydrolysis (DH) of 5 +/- 0.5% were achieved. Analysis by far-UV
      circular dichroism showed that the denaturation was mainly promoted by the high
      temperature used during the incubation. The adequate balance between the DD and
      the DH results in an effective emulsifying property improvement for the Z19 alpha
      zein. Thus, after the deamidation treatment, the surface hydrophobicity decreased
      from 9.5 x 104 +/- 6.8 x 103 to 46 x 104 +/- 2.1 x 103, and the emulsion
      stability increased from 18 +/- 0.7% to 80 +/- 4.7% since the oil globules
      stabilized by the modified protein were smaller (57.7 +/- 5.73 nm) and more
      resistant to coalescence than those present in the native protein emulsions (1488
      +/- 3.92 nm).

PMID- 17227078
TI  - Slow-binding inhibition of soybean lipoxygenase-1 by dodecyl gallate.
AB  - Dodecyl gallate inhibited the soybean lipoxygenase-1 (EC 1.13.11.12, type-1)
      catalyzed peroxidation of linoleic acid with an IC50 of 0.007 microM without
      being oxidized. The progress curves for enzyme reactions were recorded by both
      spectrophotometric and polarographic methods, and the inhibition kinetics
      revealed competitive and slow-binding inhibition. Both the initial velocity and
      steady-state rate in the progress curve decreased with increasing dodecyl
      gallate. The kinetic parameters that described the inhibition by dodecyl gallate
      were evaluated by nonlinear regression fits.

PMID- 17227080
TI  - Quantitation of tocotrienol and tocopherol in various rice brans.
AB  - Rice bran is abundant in bioactive compounds including tocotrienol (T3,
      unsaturated vitamin E). T3 has been reported about its potential functionalities
      (i.e., antiangiogenic effect), so much attention has been paid on usability of
      rice bran T3. Hence, we developed a rapid screening method for T3-rich rice bran
      by one-step equilibrium direct solvent extraction followed by normal phase high
      performance liquid chromatography (HPLC). The method gave high-extraction rate of
      rice bran T3 and tocopherol (above 90%), and the determination of vitamin E by
      HPLC was completed within 15 min. Using the method, an average of total T3
      content in 109 kinds of rice bran samples was 830 mug/g dry wt. Kouchi-Akamai,
      Joushuu, and Wataribune were found as the T3-rich rice bran varieties (1350-1430
      microg T3/g dry wt). According to T3 ratio against total vitamin E (wt %), the
      average ratio was 61%. Hirayama, Moritawase, and Kaneko were found as the
      varieties having the highest T3 ratio (80-86%). Since T3 content in Koshihikari
      rice bran (the leading variety in Japan) was a little above the average, we cross
      fertilized Koshihikari with T3-rich varieties and found that T3 content or ratio
      in F1 was improved compared with Koshihikari. The varieties found rich in T3
      could be used for nutraceutical purpose.

PMID- 17227079
TI  - Diet alters the fatty acid composition of individual phospholipid classes in beef
      muscle.
AB  - The objective of this study was to investigate the effect of diet on the
      distribution of phospholipid classes and fatty acid profiles of individual
      phospholipid classes in longissimus muscle of beef. An experiment was established
      to examine the effect of pasture-based versus concentrate diet offered to two
      different breeds (German Holstein and German Simmental bulls) to enhance the
      content of beneficial fatty acids in beef and improve the meat quality for the
      consumer. High-performance thin-layer chromatography was utilized to separate the
      phospholipid classes. The fatty acid composition of the individual phospholipid
      classes was determined by gas chromatography. The main phospholipid classes in
      the muscle were phosphatidylethanolamine and phosphatidylcholine, representing
      approximately 60% of the total phospholipids, followed by phosphatidylinositol
      ranging between 11.8 and 14.8%. The results have shown that the fatty acid
      profiles in the detected seven phospholipid classes can be affected by different
      feeding systems. Pasture-based feeding resulted in an enrichment of total and
      individual n-3 fatty acids in all phospholipid classes of muscle lipids of bulls
      compared with those fed on concentrate. In contrast, pasture-based diet
      significantly decreased the proportion of total and individual n-6 fatty acids in
      phospholipid classes, except in the sphingomyelin fraction. The total saturated
      fatty acid proportions in the phospholipid classes were different and ranged
      between 4.5% in the cardiolipin fraction and 50.5% in the sphingomyelin fraction
      of muscle lipids of bulls. Furthermore, the diet effects on the saturated fatty
      acid proportion in the different phospholipid classes differ widely. The results
      have shown that the C18:1 trans and CLA profiles in the detected seven
      phospholipid classes can be affected by different feeding systems.

PMID- 17227081
TI  - Proteomic response to intracellular proteins of Monascus pilosus grown under
      phosphate-limited complex medium with different growth rates and pigment
      production.
AB  - Monascus pigments are important colorings in food applications. Rice containing
      potassium phosphate and sodium nitrate was reported as a good pigment-producing
      medium for Monascus in previous studies. We found that the lack of potassium
      phosphate in this medium depressed red pigment production in cultivated Monascus
      pilosus. However, the influence of phosphate limitation on the biochemical
      metabolisms concerning culture growth and pigment production in Monascus remains
      unknown. Here, we used proteomic analysis by two-dimensional gel electrophoresis,
      matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass
      spectrometry (MALDI-TOF/TOF MS), tandem mass spectrometry (MS/MS), and database
      interrogation to separate and identify the proteins of M. pilosus grown between
      the lack of potassium phosphate and the control media. Phosphate limitation to
      this complex medium induced an up-regulation of aldehyde dehydrogenase and
      several glycolytic enzymes in Monascus relative to the control. In contrast, the
      metabolic enzymes such as glucosamine:fructose-6-phosphate aminotransferase and
      ADP-ribosylation factor 1 were up-regulated in the control.

PMID- 17227082
TI  - Impact of electrostatic interactions on formation and stability of emulsions
      containing oil droplets coated by beta-lactoglobulin-pectin complexes.
AB  - Interfacial protein-polysaccharide complexes can be used to improve the physical
      stability of oil-in-water emulsions. The purpose of this study was to examine the
      impact of ionic strength on the formation and stability of oil-in-water emulsions
      containing polysaccharide-protein-coated droplets. Emulsions were prepared that
      contained 0.1 wt % corn oil, 0.05 wt % beta-lactoglobulin, and 0.02 wt % pectin
      at pH 7. The emulsions were then adjusted to pH 4 to promote electrostatic
      deposition of the pectin molecules onto the surfaces of the protein-coated
      droplets. The salt concentration of the aqueous phase (0 or 50 mM NaCl) was
      adjusted either before or after deposition of the pectin molecules onto the
      droplet surfaces. We found that stable emulsions containing polysaccharide
      protein-coated droplets could be formed when the salt was added after pectin
      adsorption but not when it was added before pectin adsorption. This phenomenon
      was attributed to the ability of NaCl to promote droplet flocculation in the
      protein-coated droplets so that the pectin molecules adsorbed onto the surfaces
      of flocs rather than individual droplets when salt was added before pectin
      adsorption. We also found that polysaccharide-protein-coated droplets had a much
      improved stability to salt-induced flocculation than protein-coated droplets with
      the same droplet charge (zeta-potential). Theoretical predictions indicated that
      this was due to the ability of the adsorbed polysaccharide layer to strongly
      diminish the van der Waals attraction between the droplets.

PMID- 17227083
TI  - Model studies on acrylamide generation from glucose/asparagine in aqueous
      glycerol.
AB  - Acrylamide formation from asparagine and glucose in different ratios in neutral
      glycerol/water mixtures was found to increase with decreasing water activity
      (0.33 < or = aw < or = 0.71 investigated) and increasing temperature (120 degrees
      C < or = T < or = 160 degrees C investigated). The initial rate of acrylamide
      formation was found to be approximately proportional to the asparagine
      concentration for an excess of asparagine, but less dependent on an excess of
      glucose. A steady-state concentration of acrylamide was established at 160
      degrees C after 1 h for aw = 0.33 (30 microg x L-1 for GLU:ASN = 10:1, 11 microg
      x L-1 for GLU:ASN = 1:1, and 130 microg x L-1 for GLU:ASN = 1:10) and for aw =
      0.47 (15 microg x L-1 for GLU:ASN = 10:1 and 80 microg x L-1 for GLU:ASN = 1:10),
      suggesting a protection by glucose against acrylamide degradation. The energy of
      activation, as estimated from the temperature dependence of the initial rate,
      increased with decreasing aw despite a higher rate of formation of acrylamide at
      low aw. For high aw, water elimination from a reaction intermediate is suggested
      to be rate determining. For low aw, the increase in energy of activation (and
      enthalpy of activation) is accordingly counteracted by a more positive entropy of
      activation, in agreement with decarboxylation as rate determining at low aw.

PMID- 17227084
TI  - Production of lactoferricin and other cationic peptides from food grade bovine
      lactoferrin with various iron saturation levels.
AB  - Purification of lactoferricin (Lfcin), a cationic antimicrobial peptide, was
      achieved by peptic digestion of food grade bovine lactoferrin (LF) followed by
      fractionation on an industrial grade cation exchange resin with stepwise salt
      gradient elution. The digest and eluted fractions were partially characterized by
      MALDI-ToF MS and N-terminal sequencing. A fraction eluted using phosphate buffer
      with 2.0 M NaCl contained predominantly two peptides with masses of 3196 and 3124
      Da, which corresponded to the 26- and 25-amino acid peptides FKCRR WQWRM KKLGA
      PSITC VRRAF (A), containing the Lfcin sequence. Putative sequences of cationic
      peptides in other eluted fractions included FKNKS RSFQ, WRMKK LGAPS ITCVR RA, and
      GAPSI TCVRR AFALE CIRAI AEKKA. The iron saturation level of LF had no effect on
      the production of Lfcin. Nevertheless, the digestion of LF containing lower iron
      content led to the production of a higher quantity of low molecular weight
      cationic peptides. A two-step process using industrial grade cation exchange
      resin led to 35% recovery of Lfcin and also produced other cationic peptides with
      potential bioactive properties.

PMID- 17227085
TI  - Influence of heating on oil-in-water emulsions prepared with soybean soluble
      polysaccharide.
AB  - The effect of heating on the physicochemical properties of emulsions prepared
      with soybean soluble polysaccharide (SSPS) was investigated. The emulsions were
      stable after heating at 90 degrees C for up to 30 min. Heating at different pH
      values or in the presence of CaCl2 (<10 mM) did not affect the stability;
      however, at higher concentrations of calcium ions, the emulsion particle size
      increased. Two fractions, a high molecular weight (HMF) and a low molecular
      weight (LMF) fraction, were separated from the crude SSPS preparation by gel
      fitration. Emulsions prepared with SSPS/HMF (MW = 310-420 kDa) showed little
      change in size with heating, while the protein impurities of the SSPS/LMF
      fraction formed aggregates by heating at pH 7. Analysis of the heat-induced
      aggregation of the two fractions of SSPS suggested that the changes in SSPS
      functionality with heating can be attributed to the protein impurities (LMF)
      present in the SSPS.

PMID- 17227086
TI  - Investigations on the effects of growth rate and dietary vitamin C on skeletal
      muscle collagen and hydroxylysyl pyridinoline cross-link concentration in farmed
      Atlantic salmon (Salmo salar).
AB  - We have investigated the interactions between dietary vitamin C levels (at 33,
      79, 135, and 424 mg kg-1 of wet mass feed) and growth rate on the collagen and
      cross-link contents of fast muscle in farmed juvenile Atlantic salmon (Salmo
      salar L.). The growth rate was measured over an 11 week period using the thermal
      growth coefficient (TGC). Alkaline-soluble (0.1 M NaOH) (a-s) hydroxyproline
      (HYP) and alkaline-insoluble (i-s) HYP were determined as a measure of collagen
      content and hydroxylysyl pyridinoline (PYD) as a measure of mature collagen cross
      link concentration. There was a approximately 5-fold increase in muscle vitamin C
      concentration at similar feed conversion ratios ( approximately 0.82) as dietary
      vitamin C levels increased from 39 to 424 mg kg-1 of wet mass feed. However, even
      the lowest dietary vitamin C was sufficient for normal skeletal development and
      growth. The lowest dietary vitamin C level tested resulted in a approximately 27%
      decrease in the a-sHYP concentration relative to the other diets, whereas there
      was no significant effect of vitamin C on the i-sHYP and PYD concentrations.
      ANOVA revealed no significant interaction between vitamin C and growth rate,
      whereas the covariate TGC was significant for i-sHYP and PYD but not for a-sHYP.
      Pyridinoline cross-link and i-s HYP concentrations were 11.1 and 7.7% lower,
      respectively, in high (TGC > 3.9) mass than low (TGC < 3.9) growth rate fish.
      These small differences in collagen cross-linking were associated with a 15.6%
      decrease in fillet firmness measured with an instrumental texture analyzer. It
      was concluded that for healthy juvenile salmon reared under controlled growth
      conditions, the dietary vitamin C inclusion of 79 mg kg-1 of wet mass feed was
      sufficient to produce the required synthesis of soluble muscle collagen.
      Furthermore, post-translational modifications of the collagen leading to cross
      linking showed a small decrease with increasing growth rate but was independent
      of vitamin C concentration in the diet at these levels.

PMID- 17227087
TI  - Determination of selenium bioavailability from wheat mill fractions in rats by
      using the slope-ratio assay and a modified torula yeast-based diet.
AB  - Selenium is an essential mineral micronutrient for animals, and significant
      evidence supports an association between supranutritional Se intake and a
      reduction in the incidence of some forms of cancer. Thus, supplemental Se intake
      may provide an avenue for reducing cancer incidence. However, an important issue
      to consider is the form of Se that should be provided in such a supplement,
      because the bioavailability and bioactivity of Se can vary dramatically depending
      on the chemical form in which it is delivered. Because wheat products are the
      largest source of Se in U.S. diets, the absorption of Se was evaluated in
      different fractions of milled wheat that exhibits very high Se levels, owing to
      its production on naturally Se-rich soils. An experiment was conducted to
      determine the bioavailability of Se from three milled fractions of high-Se wheat.
      The method used was the slope-ratio assay, which measures the ability of Se from
      the wheat fractions to regenerate Se-dependent enzyme activities and tissue Se
      concentrations in Se-deficient rats. The responses generated from wheat Se were
      compared to a standard response curve generated by feeding graded amounts of Se
      as sodium selenite (Na2SeO3; NaSelenite) or selenomethionine (SeMet) in an AIN
      93G-Torula yeast-based diet. Results showed that Se from wheat flour (
      approximately 75% extraction) was nearly 100% available by a number of measures
      including plasma, liver, kidney, and muscle Se concentrations and liver and
      erythrocyte Se-dependent enzyme activities when compared with similar measures in
      rats fed NaSelenite or SeMet. However, on the basis of similar criteria, Se from
      wheat shorts was only about 85% available and that from wheat bran was about 60%
      available for absorption. These results indicate that high-Se wheat products,
      mainly those made from refined flour alone, might be particularly well suited for
      use as dietary Se supplements.

PMID- 17227088
TI  - Addition of antioxidant of bamboo leaves (AOB) effectively reduces acrylamide
      formation in potato crisps and French fries.
AB  - The present study was to demonstrate the efficiency of antioxidant of bamboo
      leaves (AOB) on the reduction of acrylamide during thermal processing and to
      summarize the optimal level of AOB applied in potato-based products. Potato
      crisps and French fries were immersed into different contents of AOB solution,
      and the frying processing parameters were optimized. The acrylamide content was
      determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The
      sensory evaluation was performed in double blind manner. Our results showed that
      nearly 74.1% and 76.1% of acrylamide in potato crisps and French fries was
      reduced when the AOB addition ratio was 0.1% and 0.01% (w/w), respectively. The
      maximum inhibitory rate was achieved when the immersion time was designed as 60
      s. Sensory evaluation results showed that the crispness and flavor of potato
      crisps and French fries processed by AOB solution had no significant difference
      compared to normal potato matrixes (P > 0.05) when the AOB addition ratio was
      <0.5% (w/w). These results suggested that AOB could significantly reduce
      acrylamide formation in potato-based foods and keep original crispness and flavor
      of potato matrixes. This study could be regarded as a pioneer contribution on the
      reduction of acrylamide in various foods by natural antioxidants.

PMID- 17227089
TI  - Toxicological and analytical investigations of noni (Morinda citrifolia) fruit
      juice.
AB  - Morinda citrifolia (noni) is known to contain genotoxic anthraquinones in the
      roots. Because of the widespread use of noni juice, the possible genotoxic risk
      was examined through a battery of short-term tests. Noni juice was also
      chemically analyzed for the possible presence of anthraquinones. Noni juice
      extract in the Salmonella microsome assay showed a slight mutagenic effect in
      strain TA1537, due to the presence of flavonoids. No mutagenicity was observed in
      the mammalian mutagenicity test with V79 Chinese hamster fibroblasts. Rats
      treated with a noni juice concentrate did not show DNA repair synthesis (UDS) in
      primary rat hepatocytes, nor could DNA adducts or DNA strand breaks be observed.
      HPLC analysis of noni juice for anthraquinones was negative, with a sensitivity
      of <1 ppm. In summary, chemical analysis and genotoxicity tests reveal that noni
      juice does not have a genotoxic potential and that genotoxic anthraquinones do
      not exist in noni juice.

PMID- 17227090
TI  - Curcuminoids form reactive glucuronides in vitro.
AB  - Curcumin is of current interest because of its putative anti-inflammatory,
      anticarcinogenic, and anti-Alzheimer's activity, but its pharmacokinetic and
      metabolic fate is poorly understood. The present in vitro study has therefore
      been conducted on the glucuronidation of curcumin and its major phase I
      metabolite, hexahydro-curcumin, as well as of various natural and artificial
      analogs. The predominant glucuronide generated by rat and human liver microsomes
      from curcumin, hexahydro-curcumin, and other analogs with a phenolic hydroxyl
      group was a phenolic glucuronide according to LC-MS/MS analysis. However, a
      second glucuronide carrying the glucuronic acid moiety at the alcoholic hydroxyl
      group was formed from the same curcuminoids, but not hexahydro-curcuminoids, by
      human microsomes. Curcuminoids without a phenolic hydroxyl group gave rise to the
      aliphatic glucuronide only. The phenolic glucuronides of curcuminoids, but not of
      hexahydro-curcuminoids, were rather lipophilic and, in part, unstable in aqueous
      solution, their stability depending strongly on the type of aromatic
      substitution. The phenolic glucuronide of curcumin and of its natural congeners,
      but not the parent compounds, clearly inhibited the assembly of microtubule
      proteins under cell-free conditions, implying chemical reactivity of the
      glucuronides. These novel properties of the major phase II metabolites of
      curcuminoids deserve further investigation.

PMID- 17227091
TI  - Detection of castor contamination by real-time polymerase chain reaction.
AB  - Due to the potential for intentional contamination of food with crude
      preparations containing ricin, a real-time PCR method was developed for the
      detection of castor plant material in ground beef. One primer pair was identified
      and confirmed to be castor-specific and efficient for amplification of ricin in
      DNA extracts from castor or beef matrices. Of three different DNA extraction
      protocols compared, the hexadecyltrimethylammonium bromide (CTAB) method yielded
      the highest quality of DNA for QPCR assay. The detection limit for castor
      contamination in ground beef samples was <0.001% (<10 microg of castor acetone
      powder per gram of beef, corresponding to 0.5 microg of ricin), indicating
      excellent sensitivity for the assay, well below the threshold for oral toxicity.

PMID- 17227092
TI  - Effect of varus/valgus malalignment on bone strains in the proximal tibia after
      TKR: an explicit finite element study.
AB  - Malalignment is the main cause of tibial component loosening. Implants that
      migrate rapidly in the first two post-operative years are likely to present
      aseptic loosening. It has been suggested that cancellous bone stresses can be
      correlated with tibial component migration. A recent study has shown that patient
      specific finite element (FE) models have the power to predict the short-term
      behavior of tibial trays. The stresses generated within the implanted tibia are
      dependent on the kinematics of the joint; however, previous studies have ignored
      the kinematics and only applied static loads. Using explicit FE, it is possible
      to simultaneously predict the kinematics and stresses during a gait cycle. The
      aim of this study was to examine the cancellous bone strains during the stance
      phase of the gait cycle, for varying degrees of varus/valgus eccentric loading
      using explicit FE. A patient-specific model of a proximal tibia was created from
      CT scan images, including heterogeneous bone properties. The proximal tibia was
      implanted with a commercial total knee replacement (TKR) model. The stance phase
      of gait was simulated and the applied loads and boundary conditions were based on
      those used for the Stanmore knee simulator. Eccentric loading was simulated. As
      well as examining the tibial bone strains (minimum and maximum principal strain),
      the kinematics of the bone-implant construct are also reported. The maximum
      anterior-posterior displacements and internal-external rotations were produced by
      the model with 20 mm offset. The peak minimum and maximum principal strain values
      increased as the load was shifted laterally, reaching a maximum magnitude for -20
      mm offset. This suggests that when in varus, the load transferred to the bone is
      shifted medially, and as the bone supporting this load is stiffer, the resulting
      peak bone strains are lower than when the load is shifted laterally (valgus). For
      this particular patient, the TKR design analyzed produced the highest cancellous
      bone strains when in valgus. This study has provided an insight in the variations
      produced in bone strain distribution when the axial load is applied
      eccentrically. To the authors' knowledge, this is the first time that the bone
      strain distribution of a proximal implanted tibia has been examined, also
      accounting for the kinematics of the tibio-femoral joint as part of the
      simulation. This approach gives greater insight into the overall performance of
      TKR.

PMID- 17227093
TI  - The biomechanics of human femurs in axial and torsional loading: comparison of
      finite element analysis, human cadaveric femurs, and synthetic femurs.
AB  - To assess the performance of femoral orthopedic implants, they are often attached
      to cadaveric femurs, and biomechanical testing is performed. To identify areas of
      high stress, stress shielding, and to facilitate implant redesign, these tests
      are often accompanied by finite element (FE) models of the bone/implant system.
      However, cadaveric bone suffers from wide specimen to specimen variability both
      in terms of bone geometry and mechanical properties, making it virtually
      impossible for experimental results to be reproduced. An alternative approach is
      to utilize synthetic femurs of standardized geometry, having material behavior
      approximating that of human bone, but with very small specimen to specimen
      variability. This approach allows for repeatable experimental results and a
      standard geometry for use in accompanying FE models. While the synthetic bones
      appear to be of appropriate geometry to simulate bone mechanical behavior, it has
      not, however, been established what bone quality they most resemble, i.e.,
      osteoporotic or osteopenic versus healthy bone. Furthermore, it is also of
      interest to determine whether FE models of synthetic bones, with appropriate
      adjustments in input material properties or geometric size, could be used to
      simulate the mechanical behavior of a wider range of bone quality and size. To
      shed light on these questions, the axial and torsional stiffness of cadaveric
      femurs were compared to those measured on synthetic femurs. A FE model,
      previously validated by the authors to represent the geometry of a synthetic
      femur, was then used with a range of input material properties and change in
      geometric size, to establish whether cadaveric results could be simulated. Axial
      and torsional stiffnesses and rigidities were measured for 25 human cadaveric
      femurs (simulating poor bone stock) and three synthetic "third generation
      composite" femurs (3GCF) (simulating normal healthy bone stock) in the midstance
      orientation. The measured results were compared, under identical loading
      conditions, to those predicted by a previously validated three-dimensional finite
      element model of the 3GCF at a variety of Young's modulus values. A smaller FE
      model of the 3GCF was also created to examine the effects of a simple change in
      bone size. The 3GCF was found to be significantly stiffer (2.3 times in torsional
      loading, 1.7 times in axial loading) than the presently utilized cadaveric
      samples. Nevertheless, the FE model was able to successfully simulate both the
      behavior of the 3GCF, and a wide range of cadaveric bone data scatter by an
      appropriate adjustment of Young's modulus or geometric size. The synthetic femur
      had a significantly higher stiffness than the cadaveric bone samples. The finite
      element model provided a good estimate of upper and lower bounds for the axial
      and torsional stiffness of human femurs because it was effective at reproducing
      the geometric properties of a femur. Cadaveric bone experiments can be used to
      calibrate FE models' input material properties so that bones of varying quality
      can be simulated.

PMID- 17227094
TI  - Finite element modeling for strain rate dependency of fracture resistance in
      compact bone.
AB  - Crack growths in compact bones driven by various strain rate levels were studied
      using finite element modeling. The energy resistance curves in bovine femur
      cortical bones were characterized, whereas the orthotropic viscoelasticity in
      bone materials was accounted for to assess the effect of strain rate on the
      energy resistance curve. The models were also used to justify the anticipated
      plane strain response as a result of rather thick specimens used in experiments.
      Similarities were found between the experimental and model results when crack
      resistance ability exhibited in bones with slow loading rates, while unstable
      crack growth existed in bones with rapid loading rates. The critical energy
      release rates slightly decreased with the increase in strain rates. The hybrid
      experimental and computational method introduced in this study could be
      beneficial for application in fracture study in which standard experiments cannot
      be validly performed.

PMID- 17227095
TI  - Thermally induced convective movements in a standard experimental model for
      characterization of lesions prior to radiofrequency functional neurosurgery.
AB  - Experimental exploration of equipment for stereotactic functional neurosurgery
      based on heating induced by radio-frequency current is most often carried out
      prior to surgery in order to secure a correct function of the equipment. The
      experiments are normally conducted in an experimental model including an albumin
      solution in which the treatment electrode is submerged, followed by a heating
      session during which a protein clot is generated around the electrode tip. The
      clot is believed to reflect the lesion generated in the brain during treatment.
      It is thereby presupposed that both the thermal and electric properties of the
      model are similar to brain tissue. This study investigates the presence of
      convective movements in the albumin solution using laser Doppler velocimetry. The
      result clearly shows that convective movements that depend on the time dependent
      heating characteristics of the equipment arise in the solution upon heating. The
      convective movements detected show a clear discrepancy compared with the in vivo
      situation that the experimental model tries to mimic; both the velocity (maximum
      velocity of about 5 mms) and mass flux are greater in this experimental setting.
      Furthermore the flow geometry is completely different since only a small fraction
      of the tissue surrounding the electrode in vivo consists of moving blood, whereas
      the entire surrounding given by the albumin solution in the experimental model is
      moving. Earlier investigations by our group (Eriksson et al., 1999, Med. Biol.
      Eng. Comput. 37, pp. 737-741; Wren, 2001, Ph.D. thesis; and Wren et al., 2001,
      Med. Biol. Eng. Comput. 39, pp. 255-262) indicate that the heat flux is an
      essential parameter for the lesion growth and final size, and that presence of
      convective movements in the model might substantially increase the heat flux.
      Thus, convective movements of the magnitude presented here will very likely
      underestimate the size of the brain lesion, a finding that definitely should be
      taken into consideration when using the model prior to patient treatment.

PMID- 17227096
TI  - Thermal detection of embedded tumors using infrared imaging.
AB  - Breast cancer is the most common cancer among women. Thermography, also known as
      thermal or infrared imaging, is a procedure to determine if an abnormality is
      present in the breast tissue temperature distribution. This abnormality in
      temperature distribution might indicate the presence of an embedded tumor.
      Although thermography is currently used to indicate the presence of an
      abnormality, there are no standard procedures to interpret these and determine
      the location of an embedded tumor. This research is a first step towards this
      direction. It explores the relationship between the characteristics (location and
      power) of an embedded heat source and the resulting temperature distribution on
      the surface. Experiments were conducted using a resistance heater that was
      embedded in agar in order to simulate the heat produced by a tumor in the
      biological tissue. The resulting temperature distribution on the surface was
      imaged using an infrared camera. In order to estimate the location and heat
      generation rate of the source from these temperature distributions, a genetic
      algorithm was used as the estimation method. The genetic algorithm utilizes a
      finite difference scheme for the direct solution of the Pennes bioheat equation.
      It was determined that a genetic algorithm based approach is well suited for the
      estimation problem since both the depth and the heat generation rate of the heat
      source were accurately predicted.

PMID- 17227097
TI  - Turbulence modeling in three-dimensional stenosed arterial bifurcations.
AB  - Under normal healthy conditions, blood flow in the carotid artery bifurcation is
      laminar. However, in the presence of a stenosis, the flow can become turbulent at
      the higher Reynolds numbers during systole. There is growing consensus that the
      transitional k-omega model is the best suited Reynolds averaged turbulence model
      for such flows. Further confirmation of this opinion is presented here by a
      comparison with the RNG k-epsilon model for the flow through a straight,
      nonbifurcating tube. Unlike similar validation studies elsewhere, no assumptions
      are made about the inlet profile since the full length of the experimental tube
      is simulated. Additionally, variations in the inflow turbulence quantities are
      shown to have no noticeable affect on downstream turbulence intensity, turbulent
      viscosity, or velocity in the k-epsilon model, whereas the velocity profiles in
      the transitional k-omega model show some differences due to large variations in
      the downstream turbulence quantities. Following this validation study, the
      transitional k-omega model is applied in a three-dimensional parametrically
      defined computer model of the carotid artery bifurcation in which the sinus bulb
      is manipulated to produce mild, moderate, and severe stenosis. The parametric
      geometry definition facilitates a powerful means for investigating the effect of
      local shape variation while keeping the global shape fixed. While turbulence
      levels are generally low in all cases considered, the mild stenosis model
      produces higher levels of turbulent viscosity and this is linked to relatively
      high values of turbulent kinetic energy and low values of the specific
      dissipation rate. The severe stenosis model displays stronger recirculation in
      the flow field with higher values of vorticity, helicity, and negative wall shear
      stress. The mild and moderate stenosis configurations produce similar lower
      levels of vorticity and helicity.

PMID- 17227098
TI  - Two mathematical models for predicting dispersion of particles in the human lung.
AB  - The dispersion of particles in the human lung is modeled as a series of virtual
      mixing tanks. Using the experimental results of Scherer et al. (1975, J. Appl.
      Physiol., 38(4), pp. 719-723) for a five-generation glass lung model, it is shown
      that each generation of the glass lung behaves like an independent virtual mixing
      tank. The corresponding resident time distribution is shown to have a variance
      approximately equal to the square of the average time a particle spends in the
      generation. By assuming that each generation of the human lung behaves as an
      independent virtual mixing tank, the realistic lung data provided by Weibel
      (1963, Morphometry of the Human Lung, Spinger-Verlag, New York) are used to
      validate this assumption in two ways. First, the half-width of the exhaled
      particle concentration profile is obtained. Second, a system of differential
      equations, with the concentration of particles in each mixing tank as its
      solution, is derived and solved numerically. This gives the exhaled concentration
      profile. Both techniques yield similar results to each other, and both give
      excellent agreement with the experimental data. The virtual mixing tank approach
      allows the complex mixing that occurs in the branching pathways of the lung to be
      more simply modeled. The model, thereby derived, is simple to change and could
      lead to enhancements in the understanding of the underlying processes
      contributing to the ventilation of the lung in health and disease.

PMID- 17227099
TI  - Support force measures of midsized men in seated positions.
AB  - Two areas not well researched in the field of seating mechanics are the
      distribution of normal and shear forces, and how those forces change with seat
      position. The availability of these data would be beneficial for the design and
      development of office, automotive and medical seats. To increase our knowledge in
      the area of seating mechanics, this study sought to measure the normal and shear
      loads applied to segmental supports in 12 seated positions, utilizing three
      inclination angles and four levels of seat back articulation that were associated
      with automotive driving positions. Force data from six regions, including the
      thorax, sacral region, buttocks, thighs, feet, and hand support were gathered
      using multi-axis load cells. The sample contained 23 midsized subjects with an
      average weight of 76.7 kg and a standard deviation of 4.2 kg, and an average
      height of 1745 mm with a standard deviation of 19 mm. Results were examined in
      terms of seat back inclination and in terms of torso articulation for
      relationships between seat positions and support forces. Using a repeated
      measures analysis, significant differences (p<0.05) were identified for normal
      forces relative to all inclination angles except for forces occurring at the hand
      support. Other significant differences were observed between normal forces behind
      the buttocks, pelvis, and feet for torso articulations. Significant differences
      in the shear forces occurred under the buttocks and posterior pelvis during
      changes in seat back inclination. Significant differences in shear forces were
      also identified for torso articulations. These data suggest that as seat back
      inclination or torso articulation change, significant shifts in force
      distribution occur.

PMID- 17227100
TI  - Electromyography of superficial and deep neck muscles during isometric,
      voluntary, and reflex contractions.
AB  - Increasingly complex models of the neck neuromusculature need detailed muscle and
      kinematic data for proper validation. The goal of this study was to measure the
      electromyographic activity of superficial and deep neck muscles during tasks
      involving isometric, voluntary, and reflexively evoked contractions of the neck
      muscles. Three male subjects (28-41 years) had electromyographic (EMG) fine wires
      inserted into the left sternocleidomastoid, levator scapulae, trapezius, splenius
      capitis, semispinalis capitis, semispinalis cervicis, and multifidus muscles.
      Surface electrodes were placed over the left sternohyoid muscle. Subjects then
      performed: (i) maximal voluntary contractions (MVCs) in the eight directions (45
      deg intervals) from the neutral posture; (ii) 50 N isometric contractions with a
      slow sweep of the force direction through 720 deg; (iii) voluntary oscillatory
      head movements in flexion and extension; and (iv) initially relaxed reflex muscle
      activations to a forward acceleration while seated on a sled. Isometric
      contractions were performed against an overhead load cell and movement dynamics
      were measured using six-axis accelerometry on the head and torso. In all three
      subjects, the two anterior neck muscles had similar preferred activation
      directions and acted synergistically in both dynamic tasks. With the exception of
      splenius capitis, the posterior and posterolateral neck muscles also showed
      consistent activation directions and acted synergistically during the voluntary
      motions, but not during the sled perturbations. These findings suggest that the
      common numerical-modeling assumption that all anterior muscles act
      synergistically as flexors is reasonable, but that the related assumption that
      all posterior muscles act synergistically as extensors is not. Despite the small
      number of subjects, the data presented here can be used to inform and validate a
      neck model at three levels of increasing neuromuscular-kinematic complexity:
      muscles generating forces with no movement, muscles generating forces and causing
      movement, and muscles generating forces in response to induced movement. These
      increasingly complex data sets will allow researchers to incrementally tune their
      neck models' muscle geometry, physiology, and feedforward/feedback
      neuromechanics.

PMID- 17227101
TI  - The relation between collagen fibril kinematics and mechanical properties in the
      mitral valve anterior leaflet.
AB  - We have recently demonstrated that the mitral valve anterior leaflet (MVAL)
      exhibited minimal hysteresis, no strain rate sensitivity, stress relaxation but
      not creep (Grashow et al., 2006, Ann Biomed Eng., 34(2), pp. 315-325; Grashow et
      al., 2006, Ann Biomed. Eng., 34(10), pp. 1509-1518). However, the underlying
      structural basis for this unique quasi-elastic mechanical behavior is presently
      unknown. As collagen is the major structural component of the MVAL, we
      investigated the relation between collagen fibril kinematics (rotation and
      stretch) and tissue-level mechanical properties in the MVAL under biaxial loading
      using small angle X-ray scattering. A novel device was developed and utilized to
      perform simultaneous measurements of tissue level forces and strain under a
      planar biaxial loading state. Collagen fibril D-period strain (epsilonD) and the
      fibrillar angular distribution were measured under equibiaxial tension, creep,
      and stress relaxation to a peak tension of 90 N/m. Results indicated that, under
      equibiaxial tension, collagen fibril straining did not initiate until the end of
      the nonlinear region of the tissue-level stress-strain curve. At higher tissue
      tension levels, epsilonD increased linearly with increasing tension. Changes in
      the angular distribution of the collagen fibrils mainly occurred in the tissue
      toe region. Using epsilonD, the tangent modulus of collagen fibrils was estimated
      to be 95.5+/-25.5 MPa, which was approximately 27 times higher than the tissue
      tensile tangent modulus of 3.58+/-1.83 MPa. In creep tests performed at 90 N/m
      equibiaxial tension for 60 min, both tissue strain and epsilonD remained constant
      with no observable changes over the test length. In contrast, in stress
      relaxation tests performed for 90 min epsilonD was found to rapidly decrease in
      the first 10 min followed by a slower decay rate for the remainder of the test.
      Using a single exponential model, the time constant for the reduction in collagen
      fibril strain was 8.3 min, which was smaller than the tissue-level stress
      relaxation time constants of 22.0 and 16.9 min in the circumferential and radial
      directions, respectively. Moreover, there was no change in the fibril angular
      distribution under both creep and stress relaxation over the test period. Our
      results suggest that (1) the MVAL collagen fibrils do not exhibit intrinsic
      viscoelastic behavior, (2) tissue relaxation results from the removal of stress
      from the fibrils, possibly by a slipping mechanism modulated by noncollagenous
      components (e.g. proteoglycans), and (3) the lack of creep but the occurrence of
      stress relaxation suggests a "load-locking" behavior under maintained loading
      conditions. These unique mechanical characteristics are likely necessary for
      normal valvular function.

PMID- 17227102
TI  - Nonlinear anisotropic stress analysis of anatomically realistic cerebral
      aneurysms.
AB  - BACKGROUND: Static deformation analysis and estimation of wall stress
      distribution of patient-specific cerebral aneurysms can provide useful insights
      into the disease process and rupture. METHOD OF APPROACH: The three-dimensional
      geometry of saccular cerebral aneurysms from 27 patients (18 unruptured and nine
      ruptured) was reconstructed based on computer tomography angiography images. The
      aneurysm wall tissue was modeled using a nonlinear, anisotropic, hyperelastic
      material model (Fung-type) which was incorporated in a user subroutine in ABAQUS.
      Effective material fiber orientations were assumed to align with principal
      surface curvatures. Static deformation of the aneurysm models were simulated
      assuming uniform wall thickness and internal pressure load of 100 mm Hg. RESULTS:
      The numerical analysis technique was validated by quantitative comparisons to
      results in the literature. For the patient-specific models, in-plane stresses in
      the aneurysm wall along both the stiff and weak fiber directions showed
      significant regional variations with the former being higher. The spatial maximum
      of stress ranged from as low as 0.30 MPa in a small aneurysm to as high as 1.06
      MPa in a giant aneurysm. The patterns of distribution of stress, strain, and
      surface curvature were found to be similar. Sensitivity analyses showed that the
      computed stress is mesh independent and not very sensitive to reasonable
      perturbations in model parameters, and the curvature-based criteria for fiber
      orientations tend to minimize the total elastic strain energy in the aneurysms
      wall. Within this small study population, there were no statistically significant
      differences in the spatial means and maximums of stress and strain values between
      the ruptured and unruptured groups. However, the ratios between the stress
      components in the stiff and weak fiber directions were significantly higher in
      the ruptured group than those in the unruptured group. CONCLUSIONS: A methodology
      for nonlinear, anisotropic static deformation analysis of geometrically realistic
      aneurysms was developed, which can be used for a more accurate estimation of the
      stresses and strains than previous methods and to facilitate prospective studies
      on the role of stress in aneurysm rupture.

PMID- 17227103
TI  - Regional multiaxial mechanical properties of the porcine anterior lens capsule.
AB  - The lens capsule of the eye plays fundamental biomechanical roles in both normal
      physiological processes and clinical interventions. There has been modest
      attention given to the mechanical properties of this important membrane, however,
      and prior studies have focused on 1-D analyses of the data. We present results
      that suggest that the porcine anterior lens capsule has a complex, regionally
      dependent, nonlinear, anisotropic behavior. Specifically, using a subdomain
      inverse finite element method to analyze data collected via a new biplane video
      based test system, we found that the lens capsule is nearly isotropic (in-plane)
      near the pole but progressively stiffer in the circumferential compared to the
      meridional direction as one approaches the equator. Because the porcine capsule
      is a good model of the young human capsule, there is strong motivation to
      determine if similar regional variations exist in the human lens capsule for
      knowledge of such complexities may allow us to improve the design of surgical
      procedures and implants.

PMID- 17227104
TI  - Effects of wall calcifications in patient-specific wall stress analyses of
      abdominal aortic aneurysms.
AB  - It is generally acknowledged that rupture of an abdominal aortic aneurysm (AAA)
      occurs when the stress acting on the wall over the cardiac cycle exceeds the
      strength of the wall. Peak wall stress computations appear to give a more
      accurate rupture risk assessment than AAA diameter, which is currently used for a
      diagnosis. Despite the numerous studies utilizing patient-specific wall stress
      modeling of AAAs, none investigated the effect of wall calcifications on wall
      stress. The objective of this study was to evaluate the influence of
      calcifications on patient-specific finite element stress computations. In
      addition, we assessed whether the effect of calcifications could be predicted
      directly from the CT-scans by relating the effect to the amount of calcification
      present in the AAA wall. For 6 AAAs, the location and extent of calcification was
      identified from CT-scans. A finite element model was created for each AAA and the
      areas of calcification were defined node-wise in the mesh of the model.
      Comparisons are made between maximum principal stress distributions, computed
      without calcifications and with calcifications with varying material properties.
      Peak stresses are determined from the stress results and related to a
      calcification index (CI), a quantification of the amount of calcification in the
      AAA wall. At calcification sites, local stresses increased, leading to a peak
      stress increase of 22% in the most severe case. Our results displayed a weak
      correlation between the CI and the increase in peak stress. Additionally, the
      results showed a marked influence of the calcification elastic modulus on
      computed stresses. Inclusion of calcifications in finite element analysis of AAAs
      resulted in a marked alteration of the stress distributions and should therefore
      be included in rupture risk assessment. The results also suggest that the
      location and shape of the calcified regions--not only the relative amount--are
      considerations that influence the effect on AAA wall stress. The dependency of
      the effect of the wall stress on the calcification elastic modulus points out the
      importance of determination of the material properties of calcified AAA wall.

PMID- 17227105
TI  - A new experimental system for the extended application of cyclic hydrostatic
      pressure to cell culture.
AB  - Mechanical forces have been shown to be important stimuli for the determination
      and maintenance of cellular phenotype and function. Many cells are constantly
      exposed in vivo to cyclic pressure, shear stress, and/or strain. Therefore, the
      ability to study the effects of these stimuli in vitro is important for
      understanding how they contribute to both normal and pathologic states. While
      there exist commercial as well as custom-built devices for the extended
      application of cyclic strain and shear stress, very few cyclic pressure systems
      have been reported to apply stimulation longer than 48 h. However, pertinent
      responses of cells to mechanical stimulation may occur later than this. To
      address this limitation, we have designed a new cyclic hydrostatic pressure
      system based upon the following design variables: minimal size, stability of
      pressure and humidity, maximal accessibility, and versatility. Computational
      fluid dynamics (CFD) was utilized to predict the pressure and potential shear
      stress within the chamber during the first half of a 1.0 Hz duty cycle. To
      biologically validate our system, we tested the response of bone marrow
      progenitor cells (BMPCs) from Sprague Dawley rats to a cyclic pressure
      stimulation of 120/80 mm Hg, 1.0 Hz for 7 days. Cellular morphology was measured
      using Scion Image, and cellular proliferation was measured by counting nuclei in
      ten fields of view. CFD results showed a constant pressure across the length of
      the chamber and no shear stress developed at the base of the chamber where the
      cells are cultured. BMPCs from Sprague Dawley rats demonstrated a significant
      change in morphology versus controls by reducing their size and adopting a more
      rounded morphology. Furthermore, these cells increased their proliferation under
      cyclic hydrostatic pressure. We have demonstrated that our system imparts a
      single mechanical stimulus of cyclic hydrostatic pressure and is capable of at
      least 7 days of continuous operation without affecting cellular viability.
      Furthermore, we have shown for the first time that BMPCs respond to cyclic
      hydrostatic pressure by alterations in morphology and increased proliferation.

PMID- 17227106
TI  - A theoretical framework to analyze bend testing of soft tissue.
AB  - It has been hypothesized that repetitive flexural stresses contribute to the
      fatigue-induced failure of bioprosthetic heart valves. Although experimental
      apparatuses capable of measuring the bending properties of biomaterials have been
      described, a theoretical framework to analyze the resulting data is lacking.
      Given the large displacements present in these bending experiments and the
      nonlinear constitutive behavior of most biomaterials, such a formulation must be
      based on finite elasticity theory. We present such a theory in this work, which
      is capable of fitting bending moment versus radius of curvature experimental data
      to an arbitrary strain energy function. A simple finite element model was
      constructed to study the validity of the proposed method. To demonstrate the
      application of the proposed approach, bend testing data from the literature for
      gluteraldehyde-fixed bovine pericardium were fit to a nonlinear strain energy
      function, which showed good agreement to the data. This method may be used to
      integrate bending behavior in constitutive models for soft tissue.

PMID- 17227107
TI  - Altered multiaxial mechanical properties of the porcine anterior lens capsule
      cultured in high glucose.
AB  - Hyperglycemia can alter the mechanical properties of tissues through the
      formation of advanced glycation endproducts in matrix proteins that have long
      half-lives. We used a custom experimental system and subdomain finite element
      method to quantify alterations in the regional multiaxial mechanical properties
      of porcine lens capsules that were cultured for 8 or 14 weeks in high glucose
      versus control media. Findings revealed that high glucose significantly stiffened
      the capsules in both the circumferential and the meridional directions, but it
      did not affect the known regional variations in anisotropy. Such information
      could be important in the design of both improved clinical procedures and
      intraocular implants for diabetic patients.

PMID- 17227108
TI  - Renal cell carcinoma with rhabdoid features: an aggressive neoplasm with
      overexpression of p53.
AB  - CONTEXT: Adult renal cell carcinoma (RCC) with rhabdoid features is a recently
      recognized morphologic variant of kidney carcinoma. To date, only very few
      studies have been published on this subject and p53 was not previously studied.
      OBJECTIVE: To evaluate clinical attributes, morphology, and immunohistochemistry
      in RCC with rhabdoid component. DESIGN: Reviewing a consecutive series of 310
      RCCs, we identified 14 cases of RCC with rhabdoid features. All cases were
      reviewed and subjected to detailed clinical and pathologic studies with
      immunohistochemical evaluation of p53. RESULTS: All tumors were clear RCCs with
      rhabdoid component representing from 5% to 50% of the tumor volume. Rhabdoid
      cells were large with a central eosinophilic intracytoplasmic inclusion and an
      eccentric atypical nucleus. Tumor necrosis was common (13/14) and sometimes
      extensive. Nine of 14 tumors were staged pT3, 4 of 14 were pT2, and only 1 tumor
      was pT1. On immunohistochemistry, rhabdoid cells were positive for vimentin (14/
      14), epithelial membrane antigen (11/14), and cytokeratin (9/14). Desmin and
      smooth muscle actin were always negative. p53 was positive in 10 of 14 tumors in
      the rhabdoid areas (5%-50% of tumor cells stained) but only in 5 of 14 cases in
      usual clear renal cell areas. In the follow-up, 10 of 14 patients developed
      metastases and 6 of 14 died of the disease. The median of survival was 8 months.
      CONCLUSIONS: We showed that RCC with rhabdoid features is a very aggressive
      neoplasm with a poor prognosis. We observed an overexpression of p53 in the
      rhabdoid component that may be implicated in the tumor dedifferentiation.

PMID- 17227109
TI  - Prospective step sections for small skin biopsies.
AB  - CONTEXT: In our laboratory, for small skin biopsies or curetted specimens, 3
      slides are prepared before the case is reviewed by the dermatopathologist.
      OBJECTIVE: To examine the utility of these "prospective" step sections in
      improving diagnostic accuracy and turnaround time. DESIGN: Five hundred
      consecutive cases, in which step sections had been cut prior to slide review,
      were studied. For each specimen, 3 slides, each consisting of 1 ribbon of tissue
      containing 4 to 6 sections, were obtained at 50-microm intervals from the
      paraffin block. RESULTS: Fifty-eight biopsies (12%) were nondiagnostic using
      slide 1 alone. Step sections provided a diagnosis in 19 of 58 cases. In an
      additional 15 cases (3%) in which a diagnosis was possible using slide 1, deeper
      levels resulted in a change in diagnosis. Thus, in 34 (7%) of 500 biopsies,
      deeper levels resulted in improved diagnostic accuracy. In addition, the
      pathologist would have ordered step sections in a further 117 cases (23%) to
      clarify the diagnosis rendered on level 1 or to exclude other lesions. Thus, 30%
      of small skin biopsies would have required deeper levels if step sections had not
      been obtained prior to slide review. CONCLUSIONS: In our laboratory, the use of
      prospective step sections is essentially cost-neutral and case turnaround time is
      improved by 9% to 45%. Step sections result in a changed diagnosis in 7% of small
      skin biopsy specimens.

PMID- 17227110
TI  - Application of a combined protocol for rational request and utilization of
      antibody assays improves clinical diagnostic efficacy in autoimmune rheumatic
      disease.
AB  - CONTEXT: Because of a marked increase in the number of requests for antinuclear
      antibodies, anti-extractable nuclear antigen antibodies, and anti-double-stranded
      DNA antibodies for the diagnosis of autoimmune rheumatic disease, guidelines have
      been proposed for their appropriate use. OBJECTIVE: To evaluate in terms of
      clinical efficacy and cost-benefit ratio the outcome of applying a protocol for
      the diagnosis of autoimmune rheumatic disease. DESIGN: A diagnostic protocol for
      the rational utilization of second-level tests (anti-extractable nuclear antigen
      antibodies and anti-double-stranded DNA antibodies) was applied at Hospital
      Polyclinic beginning January 2004. The appropriateness of 685 consecutive
      requests received at the clinical pathology laboratory from January to June 2004
      was assessed. Patients who underwent these laboratory tests were followed up for
      12 months after blood sample drawing. RESULTS: Introduction of the protocol led
      to a significant reduction in the number of second-level tests prescribed (27.9%
      vs 49.5% for anti-extractable nuclear antigen antibodies; 27.5% vs 56.6% for anti
      double-stranded DNA antibodies). After the period of observation, none of the 163
      patients who had negative results on the first-level test and were asymptomatic,
      for whom second-level tests had not therefore been performed, were found to have
      autoimmune rheumatic disease. In 90.5% (77/85) of patients positive for the
      second-level tests, clinical confirmation of autoimmune rheumatic disease was
      obtained. CONCLUSIONS: Not only did application of the diagnostic protocol reduce
      the number of second-level tests performed but it also increased their
      specificity. Our data thus indicate that the use of shared guidelines by clinical
      and laboratory specialists yields satisfactory results.

PMID- 17227111
TI  - Human leukocyte antigen alleles and haplotypes associated with chronicity of
      hepatitis B virus infection in Koreans.
AB  - CONTEXT: Chronic hepatitis B infection is the leading cause of cirrhosis and
      hepatocellular carcinoma. Human leukocyte antigen may be involved in the
      chronicity of hepatitis B virus (HBV) infection. OBJECTIVE: To analyze the
      association between HBV chronicity and human leukocyte antigen alleles and
      haplotypes of 636 organ donors and recipients. DESIGN: Subjects were categorized
      into 2 groups according to their clinical and serologic profiles, specifically,
      an HBV natural convalescent group and an HBV chronic carrier (CC) group. RESULTS:
      Hepatitis B chronicity was positively associated with A33 (P = .004, odds ratio
      [OR] = 1.59) and DR7 (P < .001, OR = 2.58), and negatively associated with HLA
      DR13 (P < .001, OR = 0.40). Coexpression of A33 and DR7 was significantly higher
      in the CC group (OR = 3.63), compared with that of either allele alone (OR = 1.76
      in A33; OR = 2.53 in DR7). The statistically significant haplotypes were B44-DR7
      (P < .001, OR = 5.44), A33-DR7 (P < .001, OR = 4.47), and A33-B44-DR7 (P < .001,
      OR = 7.31) in the CC group. CONCLUSIONS: Our results indicate that alleles of
      A33, DR7, and haplotypes containing DR7 are associated with HBV chronicity among
      Koreans. Moreover, the 2 antigens had an additive effect on chronicity. These
      findings support the theory that human leukocyte antigen class I-restricted
      cytotoxic T cells and human leukocyte antigen class II-restricted helper T cells
      play an important role in HBV chronicity.

PMID- 17227112
TI  - Differential expression of melanocytic markers in myoid, lipomatous, and vascular
      components of renal angiomyolipomas.
AB  - CONTEXT: Renal angiomyolipoma is a tumor composed of varying amounts of fat,
      smooth muscle, and blood vessels. Characteristically, tumor cells express
      melanocytic markers such as HMB-45 and Melan-A. Recently, several other markers
      have been described as having excellent diagnostic sensitivity in cutaneous
      melanocytic lesions. OBJECTIVES: To compare the sensitivities of 5 melanocytic
      markers in renal angiomyolipoma and to study the expression patterns of these
      markers in the 3 different components of angiomyolipoma. DESIGN: A tissue
      microarray of 20 renal angiomyolipomas was constructed. For each case, 3 cores
      containing fat, blood vessels, and smooth muscle were taken. The tissue
      microarray was then stained for HMB-45, Melan-A, tyrosinase, NK1-C3, and CD117.
      RESULTS: HMB-45 was positive in 95%, Melan-A in 85%, NK1-C3 in 70%, tyrosinase in
      50%, and CD117 in 40% of the cases. All (20/20) were positive for HMB-45 and
      Melan-A combined. These 5 markers had different sensitivities in the 3
      components. HMB-45 was positive in 90%, 85%, and 80% of fat, smooth muscle, and
      blood vessel components, respectively; Melan-A in 70%, 60%, and 40%; NK1-C3 in
      55%, 55%, and 45%; tyrosinase in 30%, 40%, and 10%; and CD117 in 20%, 40%, and
      10%, respectively, of these 3 components. CONCLUSIONS: HMB-45 and Melan-A
      combined were positive in 100% of the renal angiomyolipomas. We recommend the use
      of these 2 markers in the workup of this entity, including those with
      predominantly 1 component. Other melanocytic markers are of limited use. A tissue
      block comprising predominantly fat or smooth muscle components should be used
      when performing melanocytic marker immunostain.

PMID- 17227113
TI  - Differential expression of kinase genes in primary hyperparathyroidism: adenoma
      versus normal and hyperplastic parathyroid tissue.
AB  - CONTEXT: Differentiation between adenoma and hyperplasia or even normal
      parathyroid tissue is difficult and based mainly on the surgeon's skill.
      Exploration of genes that express differentially in these various tissues using
      microarrays and other sophisticated research tools will enable identification and
      perhaps development of new methods of perioperative diagnosis. OBJECTIVE: To
      assemble a panel of kinase genes to differentiate parathyroid adenoma from normal
      and hyperplastic parathyroid tissue. DESIGN: RNA was extracted from adenoma,
      hyperplasia, and normal parathyroid tissue and hybridized to a microarray
      containing 359 human cDNAs of known kinase genes. Signals of exposure were
      scanned and quantified with software for digital image analysis. Semiquantitative
      reverse transcriptase polymerase chain reaction analysis of sample genes was
      performed, up-regulated or down-regulated, to validate the microarray results.
      RESULTS: The ratio values considered significant (<0.5 or >1.5) suggest that
      genes up-regulated in parathyroid adenoma are those responsible for blood vessel
      angiogenesis and genes belonging to the cyclin-dependent kinase inhibitor groups.
      Genes down-regulated in parathyroid adenoma are related to cellular growth and
      apoptosis--genes from the mitogen-activated protein kinase group and DNA
      dependent protein kinase group. An interesting gene down-regulated in the
      parathyroid adenoma samples is related to the serine/threonine protein kinases
      that exert a key function in calcium handling. A panel of 5 genes was defined:
      p19, p21 and the gene for vascular endothelial growth factor from the up
      regulated group, and the gene for protein kinase C and SGK from the down
      regulated group. Reverse transcriptase polymerase chain reaction confirmed the
      microarray results for these genes. CONCLUSIONS: The kinase genes panel presented
      can be used to differentiate parathyroid adenoma from normal and hyperplastic
      parathyroid tissue in particular when histopathology fails to provide a decisive
      diagnosis.

PMID- 17227114
TI  - Placental mesenchymal dysplasia.
AB  - CONTEXT: Placental mesenchymal dysplasia is characterized by placentomegaly and
      may be mistaken for molar pregnancy both clinically and macroscopically because
      of the presence of "grapelike vesicles." It may be associated with a completely
      normal fetus, a fetus with growth restriction, or a fetus with features of
      Beckwith-Wiedemann syndrome. OBJECTIVE: To review the etiology, molecular
      pathology, gross and microscopic features, clinical presentation, complications,
      and differential diagnosis of placental mesenchymal dysplasia. DATA SOURCES: The
      PubMed and the Medline databases were systematically searched for articles
      between 1970 and 2006. The following keywords were used: placental mesenchymal
      dysplasia, mesenchymal hyperplasia, molar pregnancy, pseudomolar pregnancy,
      Beckwith-Wiedemann syndrome, and placentomegaly. Relevant references from review
      articles were also searched. CONCLUSIONS: Placental mesenchymal dysplasia should
      be considered in the differential diagnosis when the ultrasonographic findings
      show a cystic placenta. Close attention should be paid to fetal morphology for
      early recognition of fetal complications and to prevent unnecessary termination
      of pregnancy in cases associated with a normal fetus.

PMID- 17227115
TI  - Primary peritoneal serous borderline tumors.
AB  - CONTEXT: Primary peritoneal serous borderline tumor is a rare epithelial
      proliferation that can present as an incidental finding at laparotomy and raises
      concern for a primary ovarian tumor with peritoneal implants. OBJECTIVE: To
      present a brief history of this condition and describe its distinctive histology
      and clinical presentation, as well as to review the chief differential diagnostic
      considerations, to include mesothelial proliferations, endosalpingiosis,
      endometriosis, high-grade primary peritoneal papillary serous carcinoma, and
      implants from primary ovarian serous neoplasms. DATA SOURCES: Relevant articles
      indexed in PubMed (National Library of Medicine) between 1966 and 2005,
      references thereof, and reference surgical pathology texts. CONCLUSIONS: Primary
      peritoneal serous borderline tumor should be considered in the differential
      diagnosis of an epithelial proliferation with prominent psammoma bodies on the
      peritoneal surface of specimens submitted for nongynecologic complaints.

PMID- 17227116
TI  - Nephrogenic systemic fibrosis mimicking inflammatory breast carcinoma.
AB  - Nephrogenic systemic fibrosis, previously known as nephrogenic fibrosing
      dermopathy, is a newly recognized systemic fibrosing disorder primarily affecting
      patients with chronic renal failure. Patients with skin involvement often develop
      papules and plaques with peau d'orange surface changes. The lower extremities and
      trunk are most commonly affected. The most important histologic differential
      diagnosis is with scleromyxedema. To our knowledge, we report the first case of
      nephrogenic systemic fibrosis involving the breasts of a 61-year-old woman with
      end-stage renal disease, clinically mimicking inflammatory breast carcinoma. We
      propose that nephrogenic systemic fibrosis be considered in the differential
      diagnosis as a rare possibility when cutaneous changes in the breast suggest
      inflammatory breast carcinoma in a patient with renal failure.

PMID- 17227117
TI  - Agranular CD4+/CD56+ hematodermic neoplasm: a distinct entity described in the
      recent World Health Organization-European Organization for Research and Treatment
      of Cancer classification for cutaneous lymphomas.
AB  - Agranular CD4+/CD56+ hematodermic neoplasm is a distinct form of lymphoma with
      aggressive behavior and marked predilection for cutaneous involvement. Because of
      CD56 positivity, natural killer cells were initially suggested as the cell of
      origin in this tumor. In the recent World Health Organization-European
      Organization for Research and Treatment of Cancer classification, the term
      blastic natural killer cell lymphoma has been replaced with CD4+/CD56+
      hematodermic neoplasm because of its derivation from a plasmacytoid dendritic
      cell precursor. Clinicopathologic features, immunohistochemical features, and
      differential diagnosis of this rare neoplasm with emphasis on the recent World
      Health Organization-European Organization for Research and Treatment of Cancer
      classification are discussed.

PMID- 17227118
TI  - Clear cell sarcoma of tendons and aponeuroses: a review.
AB  - Clear cell sarcoma of tendons and aponeuroses, also referred to as malignant
      melanoma of soft parts, is a rare malignancy derived from neural crest cells. It
      usually presents in the distal lower extremities of young adults, frequently
      attached to tendons or aponeuroses. It behaves like a high-grade soft tissue
      sarcoma and is associated with poor overall survival. Magnetic resonance imaging
      studies of the lesion reveal T1 hypointensity, T2 hyperintensity, and gadolinium
      uptake. Grossly, the tumor is usually circumscribed with a histologic pattern of
      uniform polygonal to fusiform cells with clear to pale eosinophilic cytoplasm
      divided into variably sized clusters by fibrous septa. Immunohistochemical
      studies in most cases show that the neoplastic cells are positive with HMB-45 and
      react with antibody against S100 protein. Most cases show a reciprocal
      cytogenetic translocation t(12;22)(q13;q12) that creates a unique chimeric fusion
      EWSR1/ATF1 gene transcript. Metastasis occurs mainly to regional lymph nodes and
      lungs. Poor prognostic indicators include a tumor size equal to or more than 5
      cm, presence of metastasis, and necrosis. The mainstay of treatment is wide
      excision of the tumor. The use of sentinel lymph node biopsy may become an
      important procedure in detecting occult regional metastasis and guiding the
      extent of surgery. The beneficial effects of adjuvant chemotherapy and
      radiotherapy have not been fully evaluated. This article provides a short
      overview of the current knowledge of clear cell sarcoma of tendons and
      aponeuroses.

PMID- 17227120
TI  - Pseudocysts may be seen in immunoglobulin G4-associated autoimmune pancreatitis.

PMID- 17227121
TI  - De novo membranous nephropathy in renal allografts with unusual histology.

PMID- 17227122
TI  - Assessment monitoring of laboratory critical values: a College of American
      Pathologists Q-Tracks study of 180 institutions.
AB  - CONTEXT: Critical laboratory value reporting is a highly visible and essential
      key activity for clinical laboratories. OBJECTIVE: To measure critical laboratory
      value reporting in multiple institutions over time and to examine the practice
      patterns and demographic factors associated with sustained improvement in
      critical value reporting. DESIGN: A longitudinal cohort study of 180 clinical
      laboratories that provided quarterly critical values reporting data for 2 to 16
      quarters was conducted using a uniform definition of successful caregiver
      notification. Mixed linear model analysis of the 2001 through 2004 dataset was
      performed. RESULTS: A decrease in total and inpatient rates of undocumented
      critical values per 1000 results was associated with (1) the American Association
      of Blood Banks inspection within the past 2 years (P = .01, for both total and
      inpatient rates); (2) unit secretary/clerical staff not authorized to accept
      inpatient critical value notification (P = .004 [total] and .001 [inpatient]);
      and (3) the mandatory practice of requiring notification of health care providers
      when handling inpatients known to have results repeatedly in the critical range
      (P = .01, for both total and inpatient rates). Continued participation in the Q
      Tracks monitoring program was associated with significant and progressive
      improvement in total, inpatient, and outpatient critical value reporting (P =
      .02, .01, and .003, respectively). CONCLUSIONS: Critical value reporting improved
      as the duration of participation in the Q-Tracks monitoring program increased.
      Improved total and inpatient critical value reporting was associated with factors
      that may be markers for institutions with priorities of quality management and
      enhanced communication with responsible caregivers.

PMID- 17227123
TI  - Flow cytometric detection of ZAP-70 in chronic lymphocytic leukemia: correlation
      with immunocytochemistry and Western blot analysis.
AB  - CONTEXT: Expression of ZAP-70 in chronic lymphocytic leukemia (CLL) predicts
      worse clinical outcome in patients with early-stage disease. It has become
      important to include ZAP-70 in the immunophenotyping panel used to diagnose CLL,
      commonly performed by flow cytometry (FC). Nevertheless, the methodology used to
      detect ZAP-70 by FC has not been extensively evaluated. OBJECTIVE: To describe
      our FC method for detecting ZAP-70 in CLL and assess whether this assay is useful
      in estimating the ZAP-70 protein level in CLL cells. DESIGN: ZAP-70 expression
      was assessed by FC in 45 consecutive newly diagnosed CLL patients, and the
      results were correlated with those of immunocytochemistry and Western blot
      analysis. RESULTS: With >25% ZAP-70-positive B cells as the cutoff, the FC
      results had a perfect concordance with those of immunocytochemistry (39/39, 100%)
      and Western blot analysis (7/7, 100%). The use of autofluorescence controls was
      found to be superior to other alternatives. Overall, 19 (42%) of 45 cases were
      ZAP-70 positive in our series. Since only 7 cases (16%) had >20% to 30% ZAP-70
      positive B cells, the cutoff of >25% readily separated CLL into positive and
      negative groups in most cases. ZAP-70 positivity was significantly associated
      with atypical morphology but not other laboratory parameters evaluated.
      CONCLUSIONS: With proper specimen processing and the use of directly fluorescence
      conjugated anti-ZAP-70 antibody, one can readily incorporate ZAP-70 into the
      routine FC study panel for CLL. Our data suggest that FC is a rapid and useful
      method to estimate the ZAP-70 protein expression level in CLL.

PMID- 17227124
TI  - Phosphorylated histone H3, Ki-67, p21, fatty acid synthase, and cleaved caspase-3
      expression in benign and atypical granular cell tumors.
AB  - CONTEXT: Granular cell tumors (GCTs) are classified as benign when none of the
      following features is present: spindling of the tumor cells, necrosis, diffuse
      pleomorphism, prominent nucleoli, high nuclear-cytoplasmic ratio, and mitotic
      rate >2 per 10 high-power fields. It has been suggested that a GCT be classified
      as atypical when 1 or 2 of these features are seen and as malignant when 3 or
      more of these are present. In our practice, we do not classify GCTs as malignant
      in the absence of metastasis. OBJECTIVE: To compare immunohistochemical staining
      for phosphorylated histone H3 (PHH3), Ki-67 (MIB-1), p21, fatty acid synthase,
      and cleaved caspase-3 in histologically classified benign and atypical GCTs.
      DESIGN: We reviewed 25 cases of GCT from our archives and classified 14 as
      atypical based on histologic features. Immunohistochemical staining for PHH3, Ki
      67, p21, fatty acid synthase, and cleaved caspase-3 was performed using standard
      methods. The number of positive cells for Ki-67, p21, and PHH3 was calculated in
      10 consecutive high-power fields in a hot spot. Fatty acid synthase and cleaved
      caspase-3 cytoplasmic expression was graded from 1 to 3. RESULTS: Ki-67 and PHH3
      scores were significantly higher in atypical GCTs. The expression of p21, fatty
      acid synthase, and cleaved caspase-3 was not significantly different between
      atypical and benign GCTs. CONCLUSIONS: This study shows that histologic features
      are reliable in identifying GCTs that have a higher proliferative potential as
      shown by higher immunoreactivity for Ki-67 and PHH3. These immunostains may help
      in classifying GCTs in cases where a thorough histologic evaluation is precluded
      by the small size of a biopsy specimen.

PMID- 17227125
TI  - Low-level genomic instability is a feature of papillary thyroid carcinoma: an
      array comparative genomic hybridization study of laser capture microdissected
      papillary thyroid carcinoma tumors and clonal cell lines.
AB  - CONTEXT: Previous chromosomal comparative genomic hybridization (CGH) studies of
      papillary thyroid carcinoma (PTC) have demonstrated a low prevalence of
      aberrations, with the majority of tumors showing no evidence of chromosomal
      instability. The technique of CGH can be optimized, however, using array CGH and
      laser capture microdissection to ensure pure cell populations for analysis.
      OBJECTIVE: To assess PTC using array CGH applied to laser capture microdissected
      tumor cells and pure cell cultures. DESIGN: Well-characterized PTC (known ret/PTC
      and BRAF mutation status), including samples from 5 tumors with classic
      morphology, 3 follicular variant tumors, and 3 clonal PTC cell lines, were
      analyzed. RESULTS: Copy gain and loss occurred in all of the tumor cases and cell
      lines examined. The most common recurrent aberrations involved gains on
      chromosomes 1, 5, 7, 11, 15, 17, and 22, with recurrent deletions occurring on
      chromosomes 4, 18, and 19. Analysis of the data from the 8 tumor samples showed
      that amplifications of TP73 (1p36.33), SNRPN (15q12), and PDGFB (22q13.1)
      occurred exclusively in tumors with a wild type BRAF. CONCLUSIONS: This study
      shows a higher prevalence of aberrations detected using array CGH allied to laser
      capture microdissection than previously described in the literature, and it
      appears that the combination of laser capture microdissection and arrayed clones
      optimizes studies utilizing CGH. Copy gain of PDGFB occurs in a subset of tumors
      showing no evidence of mutated BRAF or rearranged ret, suggesting that copy gain
      of PDGFB may underlie the increased expression of platelet-derived growth factor
      described recently in the literature.

PMID- 17227126
TI  - Analysis of loss of heterozygosity in atypical and negative bile duct brushing
      cytology specimens with malignant outcome: are "false-negative" cytologic
      findings a representation of morphologically subtle molecular alterations?
AB  - CONTEXT: Conventional cytologic evaluation of bile duct brushings for neoplasia
      has high specificity but relatively low sensitivity. OBJECTIVE: The aim of this
      pilot study was to examine whether K-ras mutations and loss of heterozygosity for
      multiple microsatellite markers in bile duct brushings would contribute to the
      detection of malignancy in cases initially reported as "negative" or "atypical."
      DESIGN: Bile duct brushing specimens with a negative or an atypical cytologic
      result (9 cases) had a benign result on the surgical pathology specimen, and 9
      additional negative or atypical cases demonstrated adenocarcinoma on the resected
      surgical specimen. Cells from representative cytopathology and histology slides
      were microdissected and analyzed for K-ras mutations and for loss of
      heterozygosity with a panel of 15 polymorphic markers on chromosomes 1p, 3p, 5q,
      9p, 9q, 10q, 17p, and 22q. RESULTS: Among cytology cases with malignant outcome,
      loss of heterozygosity or K-ras mutation was detected in 8 (88.8%) of 9 cases. In
      the corresponding 9 surgical pathology specimens with adenocarcinoma, K-ras
      mutations and/or allelic losses were detected in all (100%). Loss of
      heterozygosity or K-ras mutation was not detected in cytology cases that had a
      benign surgical outcome. The fractional allelic loss of these 9 cytology
      specimens ranged from 0 to 0.25 (mean, 0.14). This compared with the fractional
      allelic loss ranging from 0.15 to 0.42 (mean, 0.27) for the corresponding
      surgical specimens. CONCLUSIONS: This pilot study suggests that low-level
      fractional allelic loss or K-ras mutation in the negative/atypical cytology
      samples with malignant outcome is a representation of morphologically subtle
      molecular alterations.

PMID- 17227127
TI  - High incidence of chromosome 1 abnormalities in a series of 27 renal oncocytomas:
      cytogenetic and fluorescence in situ hybridization studies.
AB  - CONTEXT: It has recently been shown by cytogenetics that there is a high
      incidence of chromosome 1 abnormalities in renal oncocytomas. OBJECTIVE: To
      confirm the cytogenetic results by fluorescence in situ hybridization (FISH)
      analysis. DESIGN: Nine additional cytogenetic analyses were added to those
      reported in our recent study, with a total of 27 tumors studied, which makes it
      the largest series of renal oncocytomas studied to date by cytogenetics and/or
      FISH. We used the LSI 1p36/LSI 1q25 Dual Color Probe Set to make the analyses.
      RESULTS: In this study, combined cytogenetics and FISH showed loss of chromosome
      arm 1p1 in 48% of renal oncocytomas. By FISH, deletion of 1p36.3 was observed in
      59% of renal oncocytomas, whereas by cytogenetics, abnormality in chromosome 1
      was seen in 32% of tumors. However, the incidence of chromosome 1 abnormalities
      among 9 bilateral tumors was much higher than in single tumors (88% vs 28%,
      respectively). Loss of only the 1p36.3 site occurred in 2 renal oncocytomas with
      translocation of chromosome 1, as shown by cytogenetics. Concordance between the
      2 techniques, when they were used simultaneously to detect chromosome 1p1
      abnormality, was 82%. CONCLUSIONS: This study further confirmed our prior results
      demonstrating the widespread occurrence of chromosome 1 abnormalities in renal
      oncocytomas. Although no abnormalities in chromosome 1 in tumors with normal
      karyotypes were detected by FISH using the current set of probes, a much higher
      incidence of such abnormalities was found in bilateral tumors, suggesting that
      genetic alterations related to the development of renal oncocytoma reside in this
      region.

PMID- 17227128
TI  - Mucin expression in reactive gastropathy: an immunohistochemical analysis.
AB  - CONTEXT: Reactive gastropathy is the second most common diagnosis made on gastric
      biopsies. Increased epithelial proliferation and modifications of epithelial
      cytokeratin profile, distinct from those of Helicobacter pylori gastritis, have
      been previously reported. However, the evaluation of mucins, important components
      of the protective mucosal mucous layer, has not been reported. OBJECTIVE: To
      investigate alterations of membrane and secreted mucins in reactive gastropathy
      of various etiologies using antibodies against mucin glycoproteins. DESIGN:
      Thirty-eight gastric biopsies diagnosed as reactive gastropathy, related to
      nonsteroidal anti-inflammatory drugs (n = 18) or bile reflux (n = 6) or of
      indeterminate etiology (n = 14), were evaluated using antibodies to MUC1, MUC5AC,
      MUC6, and MUC2. All cases were confirmed to be negative for H. pylori. The
      biopsies were classified in 3 groups based on the severity of cytoarchitectural
      changes (mild, moderate, and severe). Mucin expression and its distribution were
      recorded and the results correlated with the cytoarchitectural alterations and
      etiologies. RESULTS: Loss of MUC1, either patchy or complete, was noted in 67% of
      the cases. Aberrant expression of MUC5AC in pyloric glands was observed in 81% of
      the cases, and aberrant expression of MUC6 in the upper foveolar epithelium was
      diffusely seen in 14% of the cases. Aberrant expression of MUC2 in non-goblet
      cells was observed in a single case. Aberrant expression of MUC6 was less
      extensive in the nonsteroidal anti-inflammatory drugs group than in other 2
      groups (P = .03). Concurrently, the diffuse distribution of aberrant MUC6
      expression was seen only in the cases of severe gastropathy (P = .09). There was
      no correlation between modifications in expression of other mucins and either the
      etiologies or the severity of cytoarchitectural changes. CONCLUSIONS: Expressions
      of membrane (MUC1) and secreted (MUC5AC, MUC6) mucins are frequently modified in
      reactive gastropathy. The alteration of MUC1, which is involved in cell adhesion
      and polarity, may play a role in the development of the serrated profile of
      reactive gastropathy. Milder modifications of the secreted mucins may be
      explained by the reactive/regenerative nature of the process. Importantly, theses
      changes are different from the increase in MUC6 and reduction of MUC5AC
      expression reported in H. pylori gastritis, underlying their mechanistic
      differences. It is worth noting that similar alterations of mucin expression are
      shared by various etiologies, that is, nonsteroidal anti-inflammatory drugs and
      bile reflux, consistent with the nonspecific nature of reactive gastropathy.

PMID- 17227129
TI  - The heterogeneous distribution of monosomy 3 in uveal melanomas: implications for
      prognostication based on fine-needle aspiration biopsies.
AB  - CONTEXT: The detection of monosomy 3 in uveal melanomas has repeatedly been
      associated with adverse outcome. Fine-needle aspiration biopsy is being used to
      detect monosomy 3 in these tumors, based on the assumption that this chromosomal
      abnormality is distributed homogeneously throughout the tumor. OBJECTIVE: To
      study the distribution of monosomy 3 in primary uveal melanoma by fluorescence in
      situ hybridization (FISH). DESIGN: We studied 50 enucleated eyes with uveal
      melanoma. In all 50 tumors we performed cytogenetic analysis and FISH using a DNA
      specific probe for the centromere region of chromosome 3 on cultured tumor cells.
      In addition, the percentage of tumor cells with monosomy 3 was assessed by FISH
      on nuclei, isolated from paraffin-embedded tissue and compared to results of FISH
      on regular histology sections of the paraffin-embedded tissue. RESULTS: Combining
      karyotyping and FISH on cultured cells identified monosomy 3 in 19 (38%) of 50
      tumors, whereas FISH on nuclei isolated from paraffin-embedded tissue showed 31
      (62%) of 50 as having monosomy for chromosome 3. FISH analysis on paraffin
      sections showed tumor heterogeneity for copy number of chromosome 3 in at least 7
      cases. CONCLUSIONS: FISH analysis on paraffin sections shows that heterogeneity
      of monosomy of chromosome 3 is a frequent phenomenon in uveal melanoma. FISH on
      nuclei isolated from paraffin-embedded tissue identifies a higher frequency of
      monosomy 3 than the traditional combination of karyotyping and FISH on cultured
      uveal melanoma cells. The practice of assigning patients to risk categories based
      on fine-needle aspiration biopsy samples from primary uveal melanoma may be
      subject to error based on the heterogeneous distribution of monosomy 3 in these
      tumors.

PMID- 17227130
TI  - Sensitivity of peripheral blood smear review for the diagnosis of Candida
      fungemia.
AB  - CONTEXT: Case reports have described detection of candidemia by examination of
      peripheral blood smears. It is unclear whether this method has wider
      applicability for early detection of fungemia. OBJECTIVE: To determine the
      sensitivity of smear review for detecting candidemia. DESIGN: Normal and
      cytopenic blood was spiked with increasing concentrations of yeast. Smears were
      prepared and reviewed by a pathologist and by technical staff. Staff members
      blinded to the purpose of the study first performed a routine slide review and
      then a targeted review for yeast. RESULTS: The pathologist detected isolated
      yeast forms at a concentration of 1 to 5 x 10(5) colony-forming units (CFU)/mL.
      When blinded to the purpose of the study, technical staff could detect Candida in
      most samples when the yeast concentration was 1 to 5 x 10(7) CFU/mL, but found it
      in only a small fraction of samples with lower concentrations. When asked to
      examine the smears specifically for yeast, they could detect it in most samples
      containing 1 to 5 x 10(6) CFU/mL. CONCLUSIONS: Detection of candidemia by
      peripheral blood smear examination requires a yeast concentration of 1 to 5 x
      10(5) CFU/mL or greater. This degree of fungemia is unusual; therefore, detection
      of candidemia by blood smear review will not be possible in most cases.
      Sensitivity of smear review for yeast detection is greatly increased if the
      microscopist is specifically directed to look for the presence of yeast.

PMID- 17227131
TI  - Early-life family structure and microbially induced cancer risk.
AB  - BACKGROUND: Cancer may follow exposure to an environmental agent after many
      decades. The bacterium Helicobacter pylori, known to be acquired early in life,
      increases risk for gastric adenocarcinoma, but other factors are also important.
      In this study, we considered whether early-life family structure affects the risk
      of later developing gastric cancer among H. pylori+ men. METHODS AND FINDINGS: We
      examined a long-term cohort of Japanese-American men followed for 28 y, and
      performed a nested case-control study among those carrying H. pylori or the
      subset carrying the most virulent cagA+ H. pylori strains to address whether
      family structure predicted cancer development. We found that among the men who
      were H. pylori+ and/or cagA+ (it is possible to be cagA+ and H. pylori- if the H.
      pylori test is falsely negative), belonging to a large sibship or higher birth
      order was associated with a significantly increased risk of developing gastric
      adenocarcinoma late in life. For those with cagA+ strains, the risk of developing
      gastric cancer was more than twice as high (odds ratio 2.2; 95% confidence
      interval 1.2-4.0) among those in a sibship of seven or more individuals than in a
      sibship of between one and three persons. CONCLUSIONS: These results provide
      evidence that early-life social environment plays a significant role in risk of
      microbially induced malignancies expressing five to eight decades later, and
      these findings lead to new models to explain these interactions.

PMID- 17227132
TI  - Two-year morbidity-mortality and alternatives to prolonged breast-feeding among
      children born to HIV-infected mothers in Cote d'Ivoire.
AB  - BACKGROUND: Little is known about the long-term safety of infant feeding
      interventions aimed at reducing breast milk HIV transmission in Africa. METHODS
      AND FINDINGS: In 2001-2005, HIV-infected pregnant women having received in
      Abidjan, Cote d'Ivoire, a peripartum antiretroviral prophylaxis were presented
      antenatally with infant feeding interventions: either artificial feeding, or
      exclusive breast-feeding and then early cessation from 4 mo of age. Nutritional
      counseling and clinical management were provided for 2 y. Breast-milk substitutes
      were provided for free. The primary outcome was the occurrence of adverse health
      outcomes in children, defined as validated morbid events (diarrhea, acute
      respiratory infections, or malnutrition) or severe events (hospitalization or
      death). Hazards ratios to compare formula-fed versus short-term breast-fed
      (reference) children were adjusted for confounders (baseline covariates and
      pediatric HIV status as a time-dependant covariate). The 18-mo mortality rates
      were also compared to those observed in the Ditrame historical trial, which was
      conducted at the same sites in 1995-1998, and in which long-term breast-feeding
      was practiced in the absence of any specific infant feeding intervention. Of the
      557 live-born children, 262 (47%) were breast-fed for a median of 4 mo, whereas
      295 were formula-fed. Over the 2-y follow-up period, 37% of the formula-fed and
      34% of the short-term breast-fed children remained free from any adverse health
      outcome (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI], 0.87
      1.38; p = 0.43). The 2-y probability of presenting with a severe event was the
      same among formula-fed (14%) and short-term breast-fed children (15%) (adjusted
      HR, 1.19; 95% CI, 0.75-1.91; p = 0.44). An overall 18-mo probability of survival
      of 96% was observed among both HIV-uninfected short-term and formula-fed
      children, which was similar to the 95% probability observed in the long-term
      breast-fed ones of the Ditrame trial. CONCLUSIONS: The 2-y rates of adverse
      health outcomes were similar among short-term breast-fed and formula-fed
      children. Mortality rates did not differ significantly between these two groups
      and, after adjustment for pediatric HIV status, were similar to those observed
      among long-term breast-fed children. Given appropriate nutritional counseling and
      care, access to clean water, and a supply of breast-milk substitutes, these
      alternatives to prolonged breast-feeding can be safe interventions to prevent
      mother-to-child transmission of HIV in urban African settings.

PMID- 17227133
TI  - Proteomic profiling of the amniotic fluid to detect inflammation, infection, and
      neonatal sepsis.
AB  - BACKGROUND: Proteomic analysis of amniotic fluid shows the presence of biomarkers
      characteristic of intrauterine inflammation. We sought to validate prospectively
      the clinical utility of one such proteomic profile, the Mass Restricted (MR)
      score. METHODS AND FINDINGS: We enrolled 169 consecutive women with singleton
      pregnancies admitted with preterm labor or preterm premature rupture of
      membranes. All women had a clinically indicated amniocentesis to rule out intra
      amniotic infection. A proteomic fingerprint (MR score) was generated from fresh
      samples of amniotic fluid using surface-enhanced laser desorption ionization
      (SELDI) mass spectrometry. Presence or absence of the biomarkers of the MR score
      was interpreted in relationship to the amniocentesis-to-delivery interval,
      placental inflammation, and early-onset neonatal sepsis for all neonates admitted
      to the Newborn Special Care Unit (n = 104). Women with "severe" amniotic fluid
      inflammation (MR score of 3 or 4) had shorter amniocentesis-to-delivery intervals
      than women with "no" (MR score of 0) inflammation or even "minimal" (MR score of
      1 or 2) inflammation (median [range] MR 3-4: 0.4 d [0.0-49.6 d] versus MR 1-2:
      3.8 d [0.0-151.2 d] versus MR 0: 17.0 d [0.1-94.3 d], p < 0.001). Nonetheless, a
      "minimal" degree of inflammation was also associated with preterm birth
      regardless of membrane status. There was a significant association between the MR
      score and severity of histological chorioamnionitis (r = 0.599, p < 0.001).
      Furthermore, neonatal hematological indices and early-onset sepsis significantly
      correlated with the MR score even after adjusting for gestational age at birth
      (OR for MR 3-4: 3.3 [95% CI, 1.1 to 9.2], p = 0.03). When compared with other
      laboratory tests routinely used to diagnose amniotic fluid inflammation and
      infection, the MR score had the highest accuracy to detect inflammation (white
      blood cell count > 100 cells/mm3), whereas the combination of Gram stain and MR
      score was best for rapid prediction of intra-amniotic infection (positive
      amniotic fluid culture). CONCLUSIONS: High MR scores are associated with preterm
      delivery, histological chorioamnionitis, and early-onset neonatal sepsis. In this
      study, proteomic analysis of amniotic fluid was shown to be the most accurate
      test for diagnosis of intra-amniotic inflammation, whereas addition of the MR
      score to the Gram stain provides the best combination of tests to rapidly predict
      infection.

PMID- 17227134
TI  - Ghost authorship in industry-initiated randomised trials.
AB  - BACKGROUND: Ghost authorship, the failure to name, as an author, an individual
      who has made substantial contributions to an article, may result in lack of
      accountability. The prevalence and nature of ghost authorship in industry
      initiated randomised trials is not known. METHODS AND FINDINGS: We conducted a
      cohort study comparing protocols and corresponding publications for industry
      initiated trials approved by the Scientific-Ethical Committees for Copenhagen and
      Frederiksberg in 1994-1995. We defined ghost authorship as present if individuals
      who wrote the trial protocol, performed the statistical analyses, or wrote the
      manuscript, were not listed as authors of the publication, or as members of a
      study group or writing committee, or in an acknowledgment. We identified 44
      industry-initiated trials. We did not find any trial protocol or publication that
      stated explicitly that the clinical study report or the manuscript was to be
      written or was written by the clinical investigators, and none of the protocols
      stated that clinical investigators were to be involved with data analysis. We
      found evidence of ghost authorship for 33 trials (75%; 95% confidence interval
      60%-87%). The prevalence of ghost authorship was increased to 91% (40 of 44
      articles; 95% confidence interval 78%-98%) when we included cases where a person
      qualifying for authorship was acknowledged rather than appearing as an author. In
      31 trials, the ghost authors we identified were statisticians. It is likely that
      we have overlooked some ghost authors, as we had very limited information to
      identify the possible omission of other individuals who would have qualified as
      authors. CONCLUSIONS: Ghost authorship in industry-initiated trials is very
      common. Its prevalence could be considerably reduced, and transparency improved,
      if existing guidelines were followed, and if protocols were publicly available.

PMID- 17227135
TI  - Tobacco smoke, indoor air pollution and tuberculosis: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Tobacco smoking, passive smoking, and indoor air pollution from
      biomass fuels have been implicated as risk factors for tuberculosis (TB)
      infection, disease, and death. Tobacco smoking and indoor air pollution are
      persistent or growing exposures in regions where TB poses a major health risk. We
      undertook a systematic review and meta-analysis to quantitatively assess the
      association between these exposures and the risk of infection, disease, and death
      from TB. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis
      of observational studies reporting effect estimates and 95% confidence intervals
      on how tobacco smoking, passive smoke exposure, and indoor air pollution are
      associated with TB. We identified 33 papers on tobacco smoking and TB, five
      papers on passive smoking and TB, and five on indoor air pollution and TB. We
      found substantial evidence that tobacco smoking is positively associated with TB,
      regardless of the specific TB outcomes. Compared with people who do not smoke,
      smokers have an increased risk of having a positive tuberculin skin test, of
      having active TB, and of dying from TB. Although we also found evidence that
      passive smoking and indoor air pollution increased the risk of TB disease, these
      associations are less strongly supported by the available evidence. CONCLUSIONS:
      There is consistent evidence that tobacco smoking is associated with an increased
      risk of TB. The finding that passive smoking and biomass fuel combustion also
      increase TB risk should be substantiated with larger studies in future. TB
      control programs might benefit from a focus on interventions aimed at reducing
      tobacco and indoor air pollution exposures, especially among those at high risk
      for exposure to TB.

PMID- 17227136
TI  - Parental family structure, Helicobacter pylori, and gastric adenocarcinoma.

PMID- 17227137
TI  - When is replacement feeding safe for infants of HIV-infected women?

PMID- 17227138
TI  - Authors, ghosts, damned lies, and statisticians.

PMID- 17227139
TI  - A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism.
AB  - BACKGROUND: HIV protease inhibitor (PI) therapy results in the rapid selection of
      drug resistant viral variants harbouring one or two substitutions in the viral
      protease. To combat PI resistance development, two approaches have been
      developed. The first is to increase the level of PI in the plasma of the patient,
      and the second is to develop novel PI with high potency against the known PI
      resistant HIV protease variants. Both approaches share the requirement for a
      considerable increase in the number of protease mutations to lead to clinical
      resistance, thereby increasing the genetic barrier. We investigated whether HIV
      could yet again find a way to become less susceptible to these novel inhibitors.
      METHODS AND FINDINGS: We have performed in vitro selection experiments using a
      novel PI with an increased genetic barrier (RO033-4649) and demonstrated
      selection of three viruses 4- to 8-fold resistant to all PI compared to wild
      type. These PI-resistant viruses did not have a single substitution in the viral
      protease. Full genomic sequencing revealed the presence of NC/p1 cleavage site
      substitutions in the viral Gag polyprotein (K436E and/or I437T/V) in all three
      resistant viruses. These changes, when introduced in a reference strain,
      conferred PI resistance. The mechanism leading to PI resistance is enhancement of
      the processing efficiency of the altered substrate by wild-type protease.
      Analysis of genotypic and phenotypic resistance profiles of 28,000 clinical
      isolates demonstrated the presence of these NC/p1 cleavage site mutations in some
      clinical samples (codon 431 substitutions in 13%, codon 436 substitutions in 8%,
      and codon 437 substitutions in 10%). Moreover, these cleavage site substitutions
      were highly significantly associated with reduced susceptibility to PI in
      clinical isolates lacking primary protease mutations. Furthermore, we used data
      from a clinical trial (NARVAL, ANRS 088) to demonstrate that these NC/p1 cleavage
      site changes are associated with virological failure during PI therapy.
      CONCLUSIONS: HIV can use an alternative mechanism to become resistant to PI by
      changing the substrate instead of the protease. Further studies are required to
      determine to what extent cleavage site mutations may explain virological failure
      during PI therapy.

PMID- 17227141
TI  - Author sequence and credit for contributions in multiauthored publications.

PMID- 17227140
TI  - Evolution, interactions, and biological networks.

PMID- 17227142
TI  - Stem cell promise, interrupted: how long do US researchers have to wait?

PMID- 17227143
TI  - Active spatial perception in the vibrissa scanning sensorimotor system.
AB  - Haptic perception is an active process that provides an awareness of objects that
      are encountered as an organism scans its environment. In contrast to the
      sensation of touch produced by contact with an object, the perception of object
      location arises from the interpretation of tactile signals in the context of the
      changing configuration of the body. A discrete sensory representation and a low
      number of degrees of freedom in the motor plant make the ethologically prominent
      rat vibrissa system an ideal model for the study of the neuronal computations
      that underlie this perception. We found that rats with only a single vibrissa can
      combine touch and movement to distinguish the location of objects that vary in
      angle along the sweep of vibrissa motion. The patterns of this motion and of the
      corresponding behavioral responses show that rats can scan potential locations
      and decide which location contains a stimulus within 150 ms. This interval is
      consistent with just one to two whisk cycles and provides constraints on the
      underlying perceptual computation. Our data argue against strategies that do not
      require the integration of sensory and motor modalities. The ability to judge
      angular position with a single vibrissa thus connects previously described,
      motion-sensitive neurophysiological signals to perception in the behaving animal.

PMID- 17227144
TI  - Different quaternary structures of human RECQ1 are associated with its dual
      enzymatic activity.
AB  - RecQ helicases are essential for the maintenance of chromosome stability. In
      addition to DNA unwinding, some RecQ enzymes have an intrinsic DNA strand
      annealing activity. The function of this dual enzymatic activity and the
      mechanism that regulates it is, however, unknown. Here, we describe two
      quaternary forms of the human RECQ1 helicase, higher-order oligomers consistent
      with pentamers or hexamers, and smaller oligomers consistent with monomers or
      dimers. Size exclusion chromatography and transmission electron microscopy show
      that the equilibrium between the two assembly states is affected by single
      stranded DNA (ssDNA) and ATP binding, where ATP or ATPgammaS favors the smaller
      oligomeric form. Our three-dimensional electron microscopy reconstructions of
      human RECQ1 reveal a complex cage-like structure of approximately 120 A x 130 A
      with a central pore. This oligomeric structure is stabilized under conditions in
      which RECQ1 is proficient in strand annealing. In contrast, competition
      experiments with the ATPase-deficient K119R and E220Q mutants indicate that RECQ1
      monomers, or tight binding dimers, are required for DNA unwinding. Collectively,
      our findings suggest that higher-order oligomers are associated with DNA strand
      annealing, and lower-order oligomers with DNA unwinding.

PMID- 17227145
TI  - The costs of carnivory.
AB  - Mammalian carnivores fall into two broad dietary groups: smaller carnivores (<20
      kg) that feed on very small prey (invertebrates and small vertebrates) and larger
      carnivores (>20 kg) that specialize in feeding on large vertebrates. We develop a
      model that predicts the mass-related energy budgets and limits of carnivore size
      within these groups. We show that the transition from small to large prey can be
      predicted by the maximization of net energy gain; larger carnivores achieve a
      higher net gain rate by concentrating on large prey. However, because it requires
      more energy to pursue and subdue large prey, this leads to a 2-fold step increase
      in energy expenditure, as well as increased intake. Across all species, energy
      expenditure and intake both follow a three-fourths scaling with body mass.
      However, when each dietary group is considered individually they both display a
      shallower scaling. This suggests that carnivores at the upper limits of each
      group are constrained by intake and adopt energy conserving strategies to counter
      this. Given predictions of expenditure and estimates of intake, we predict a
      maximum carnivore mass of approximately a ton, consistent with the largest
      extinct species. Our approach provides a framework for understanding carnivore
      energetics, size, and extinction dynamics.

PMID- 17227146
TI  - Discrete states of a protein interaction network govern interphase and mitotic
      microtubule dynamics.
AB  - The cytoplasm of eukaryotic cells is thought to adopt discrete "states"
      corresponding to different steady states of protein networks that govern changes
      in subcellular organization. For example, in Xenopus eggs, the interphase to
      mitosis transition is induced solely by activation of cyclin-dependent kinase 1
      (CDK1) that phosphorylates many proteins leading to a reorganization of the
      nucleus and assembly of the mitotic spindle. Among these changes, the large array
      of stable microtubules that exists in interphase is replaced by short, highly
      dynamic microtubules in metaphase. Using a new visual immunoprecipitation assay
      that quantifies pairwise protein interactions in a non-perturbing manner in
      Xenopus egg extracts, we reveal the existence of a network of interactions
      between a series of microtubule-associated proteins (MAPs). In interphase,
      tubulin interacts with XMAP215, which is itself interacting with XKCM1, which
      connects to APC, EB1, and CLIP170. In mitosis, tubulin interacts with XMAP215,
      which is connected to EB1. We show that in interphase, microtubules are stable
      because the catastrophe-promoting activity of XKCM1 is inhibited by its
      interactions with the other MAPs. In mitosis, microtubules are short and dynamic
      because XKCM1 is free and has a strong destabilizing activity. In this case, the
      interaction of XMAP215 with EB1 is required to counteract the strong activity of
      XKCM1. This provides the beginning of a biochemical description of the notion of
      "cytoplasmic states" regarding the microtubule system.

PMID- 17227147
TI  - Measurement issues associated with conditional reasoning tests: indirect
      measurement and test faking.
AB  - Conditional reasoning is a new measurement technique used to measure cognitive
      biases associated with latent personality motives. The current article describes
      3 studies examining 2 related measurement issues associated with conditional
      reasoning tests (CRTs). Study 1 examined the necessity of maintaining indirect
      assessment when administering CRTs. Results indicated that, compared with a
      control condition, 2 experimental conditions that disclosed the purpose of
      assessment yielded significant mean shifts on a CRT. Study 2 explored whether
      CRTs could be faked when the purpose of assessment was not disclosed. Results
      indicated that when indirect measurement was maintained, CRTs appeared to be
      resistant to faking. Study 3 compared scores on the Conditional Reasoning Test
      for Aggression across student, applicant, and incumbent samples. Results
      indicated no significant mean differences among these samples.

PMID- 17227148
TI  - The development of collective efficacy in teams: a multilevel and longitudinal
      perspective.
AB  - The authors developed and tested a longitudinal multilevel model of collective
      efficacy formation. In 50 self-managing student teams, they investigated the
      effects of individual-level and team-level factors on observed behaviors and the
      subsequent development of collective efficacy for mastering a complex team task.
      Self-efficacy for teamwork, task-relevant knowledge, and collective efficacy
      predicted individual teamwork behaviors (rated by peers). Aggregated measures of
      teamwork behavior were related to subsequent collective efficacy, which was
      significantly related to final team performance.

PMID- 17227149
TI  - A review of research methods in IO/OB work-family research.
AB  - A methodological review was conducted of work-family (WF) research published in
      industrial-organizational psychology and organizational behavior journals over a
      period of 24 years (1980-2003). Content analysis was conducted on 225 individual
      studies published in 210 articles to categorize methodological features,
      including the research design, sources of data used, data analysis techniques,
      reliability and validity of measures used, and sociodemographic characteristics
      of the samples. Results support many of the criticisms of WF research and suggest
      that scholars publishing WF research in industrial-organizational psychology and
      organizational behavior journals could make greater use of longitudinal and
      experimental research designs, gather more multisource data, and move beyond the
      individual level of analysis. Adopting more diverse conceptualizations of family,
      including a greater proportion of racial and ethnic minorities, and studying
      workers in occupations other than managerial or professional positions also
      appear warranted. Finally, methodological trends varied across specific WF
      content areas, which suggests that distinct methodologies might be useful to
      advance knowledge of specific WF topics.

PMID- 17227150
TI  - Commitment to family roles: effects on managers' attitudes and performance.
AB  - The authors tested the premise that family role commitment (i.e., marital role
      commitment, parental role commitment) has simultaneous negative and positive
      effects on managers' (N = 346) life satisfaction, career satisfaction, and
      performance through family-to-work interference and enhancement. The authors also
      explored whether psychological strain mediates the effects of interference and
      enhancement on outcomes. The authors expected family role commitment to reduce
      the favorability of outcomes by increasing interference. To the contrary, they
      found that neither marital nor parental role commitment was associated with
      increased interference. The authors expected family role commitment to improve
      outcomes by increasing enhancement. As expected, marital role commitment was
      associated with increased enhancement, which, in turn, seemed to reduce strain
      and strengthen outcomes. Parental role commitment was also associated with
      increased enhancement. However, parental role commitment had direct positive
      effects on outcomes that were more substantial than its indirect effects through
      enhancement. Overall, marital and parental role commitment had more benefits than
      costs.

PMID- 17227151
TI  - Work and family satisfaction and conflict: a meta-analysis of cross-domain
      relations.
AB  - This meta-analysis is a review of the literature examining the relations among
      stressors, involvement, and support in the work and family domains, work-family
      conflict, and satisfaction outside of those domains. Results suggest that a
      considerable amount of variability in family satisfaction is explained by work
      domain-specific variables, whereas a considerable amount of variability in job
      satisfaction is explained by family domain-specific variables, with job and
      family stress having the strongest effects on work-family conflict and cross
      domain satisfaction. The authors propose future directions for research on work
      and family issues focusing on other explanatory mechanisms and moderators of
      cross-domain relations.

PMID- 17227153
TI  - Why are women penalized for success at male tasks?: the implied communality
      deficit.
AB  - In 3 experimental studies, the authors tested the idea that penalties women incur
      for success in traditionally male areas arise from a perceived deficit in
      nurturing and socially sensitive communal attributes that is implied by their
      success. The authors therefore expected that providing information of communality
      would prevent these penalties. Results indicated that the negativity directed at
      successful female managers--in ratings of likability, interpersonal hostility,
      and boss desirability--was mitigated when there was indication that they were
      communal. This ameliorative effect occurred only when the information was clearly
      indicative of communal attributes (Study 1) and when it could be unambiguously
      attributed to the female manager (Study 2); furthermore, these penalties were
      averted when communality was conveyed by role information (motherhood status) or
      by behavior (Study 3). These findings support the idea that penalties for women's
      success in male domains result from the perceived violation of gender-stereotypic
      prescriptions.

PMID- 17227154
TI  - Emotional exhaustion and job performance: the mediating role of motivation.
AB  - The literature concerning the relationship between emotional exhaustion and
      performance led researchers to raise questions about the extent to which the
      variables are related. In 2 time-lagged samples, the authors found that
      motivation mediates the emotional exhaustion-job performance relationship.
      Moreover, the authors found that participants appear to target their investment
      of resources in response to emotional exhaustion to develop social support
      through social exchange; specifically, emotional exhaustion was associated with
      communion striving resources that were manifest in the form of organizational
      citizenship behaviors targeted at individuals. Implications of this relationship
      for theories of burnout and for management practice are discussed.

PMID- 17227155
TI  - Self-efficacy and work-related performance: the integral role of individual
      differences.
AB  - The present study estimated the unique contribution of self-efficacy to work
      related performance controlling for personality (the Big 5 traits), intelligence
      or general mental ability, and job or task experience. Results, based on a meta
      analysis of the relevant literatures, revealed that overall, across all studies
      and moderator conditions, the contribution of self-efficacy relative to
      purportedly more distal variables is relatively small. Within moderator
      categories, there were several cases in which self-efficacy made unique
      contributions to work-related performance. For example, self-efficacy predicted
      performance in jobs or tasks of low complexity but not those of medium or high
      complexity, and self-efficacy predicted performance for task but not job
      performance. Overall, results suggest that the predictive validity of self
      efficacy is attenuated in the presence of individual differences, though this
      attenuation does depend on the context.

PMID- 17227156
TI  - A meta-analytic examination of the goal orientation nomological net.
AB  - The authors present an empirical review of the literature concerning trait and
      state goal orientation (GO). Three dimensions of GO were examined: learning,
      prove performance, and avoid performance along with presumed antecedents and
      proximal and distal consequences of these dimensions. Antecedent variables
      included cognitive ability, implicit theory of intelligence, need for
      achievement, self-esteem, general self-efficacy, and the Big Five personality
      characteristics. Proximal consequences included state GO, task-specific self
      efficacy, self-set goal level, learning strategies, feedback seeking, and state
      anxiety. Distal consequences included learning, academic performance, task
      performance, and job performance. Generally speaking, learning GO was positively
      correlated, avoid performance GO was negatively correlated, and prove performance
      GO was uncorrelated with these variables. Consistent with theory, state GO tended
      to have stronger relationships with the distal consequences than did trait GO.
      Finally, using a meta-correlation matrix, the authors found that trait GO
      predicted job performance above and beyond cognitive ability and personality.
      These results demonstrate the value of GO to organizational researchers.

PMID- 17227157
TI  - Does a structured free recall intervention reduce the effect of stereotypes on
      performance ratings and by what cognitive mechanism?
AB  - The purpose of this article was to extend previous work on the effect of racial
      biases on performance ratings. The 1st of 2 studies examined whether a structured
      free recall intervention decreased the influence of negative racial biases on the
      performance ratings of Black men. Results indicated that without the
      intervention, raters who endorsed a negative stereotype of Black men as managers
      evaluated Black men more negatively. However, the structured free recall
      intervention successfully reduced these effects. The second study examined in
      more detail the cognitive mechanisms underlying the success of the intervention.
      Results are consistent with the assumption that the reduction of the influence of
      racial biases under structured free recall conditions is a consequence of a
      modified strength threshold for retrieval of behaviors from memory.

PMID- 17227158
TI  - The use of background and ability profiles to predict college student outcomes.
AB  - To determine whether profiles of predictor variables provide incremental
      prediction of college student outcomes, the authors 1st applied an empirical
      clustering method to profiles based on the scores of 2,771 entering college
      students on a battery of biographical data and situational judgment measures,
      along with SAT and American College Test scores and high school grade point
      average, which resulted in 5 student groups. Performance of the students in these
      clusters was meaningfully different on a set of external variables, including
      college grade point average, self-rated performance, class absenteeism,
      organizational citizenship behavior, intent to quit their university, and
      satisfaction with college. The 14 variables in the profile were all significantly
      correlated with 1 or more of the outcome measures; however, nonlinear prediction
      of these outcomes on the basis of cluster membership did not add incrementally to
      a linear-regression-based combination of these 14 variables as predictors.

PMID- 17227159
TI  - The interactive effects of recruitment practices and product awareness on job
      seekers' employer knowledge and application behaviors.
AB  - In this article, the author draws on research from the literature on marketing
      and recruitment to identify how recruitment practices and company product
      awareness are related to job seekers' application behaviors through 3 aspects of
      job seekers' employer knowledge. Based on results from a within-subject design
      with data from 123 recruiting companies and 456 student job seekers, the author's
      findings suggest that the relationships between recruitment strategies and
      application intentions and decisions are moderated by product awareness.
      Specifically, low-information recruitment practices are significantly and
      positively related to application behaviors through employer familiarity and
      employer reputation when product awareness is low. In contrast, high-information
      recruitment practices are related to job seekers' application behaviors through
      employer reputation and job information when product awareness is high.

PMID- 17227160
TI  - Antecedents and outcomes of abusive supervision: test of a trickle-down model.
AB  - The authors examined antecedents of abusive supervision and the relative
      importance of interactional and procedural justice as mediators of the
      relationship between abusive supervision and the work outcomes of affective
      organizational commitment and individual- and organization-directed citizenship
      behaviors. Data were obtained from subordinate-supervisor dyads from a
      telecommunication company located in southeastern China. Results of moderated
      regression analysis revealed that authoritarian leadership style moderated the
      relationship between supervisors' perceptions of interactional justice and
      abusive supervision such that the relationship was stronger for supervisors high
      rather than low in authoritarian leadership style. In addition, results of
      structural equation modeling analysis revealed that subordinates' perceptions of
      interactional but not procedural justice fully mediated the relationship between
      abusive supervision and the work outcomes. Implications for future investigations
      of abusive supervision are discussed.

PMID- 17227161
TI  - Leader-member exchange and member performance: a new look at individual-level
      negative feedback-seeking behavior and team-level empowerment climate.
AB  - From a basis in social exchange theory, the authors investigated whether, and
      how, negative feedback-seeking behavior and a team empowerment climate affect the
      relationship between leader-member exchange (LMX) and member performance. Results
      showed that subordinates' negative feedback-seeking behavior mediated the
      relationship between LMX and both objective and subjective in-role performance.
      In addition, the level of a team's empowerment climate was positively related to
      subordinates' own sense of empowerment, which in turn negatively moderated the
      effects of LMX on negative feedback-seeking behavior.

PMID- 17227163
TI  - Take care! The evaluation of a team-based burnout intervention program for
      oncology care providers.
AB  - In this quasi-experimental study among staff of 29 oncology wards, the authors
      evaluated the effects of a team-based burnout intervention program combining a
      staff support group with a participatory action research approach. Nine wards
      were randomly selected to participate in the program. Before the program started
      (Time 1), directly after the program ended (Time 2), and 6 months later (Time 3),
      study participants filled out a questionnaire on their work situation and well
      being. Results of multilevel analyses showed that staff in the experimental wards
      experienced significantly less emotional exhaustion at both Time 2 and Time 3 and
      less depersonalization at Time 2, compared with the control wards. Moreover,
      changes in burnout levels were significantly related to changes in the perception
      of job characteristics over time.

PMID- 17227164
TI  - Predicting workplace aggression: a meta-analysis.
AB  - The authors conducted a meta-analysis of 57 empirical studies (59 samples)
      concerning enacted workplace aggression to answer 3 research questions. First,
      what are the individual and situational predictors of interpersonal and
      organizational aggression? Second, within interpersonal aggression, are there
      different predictors of supervisor- and coworker-targeted aggression? Third, what
      are the relative contributions of individual (i.e., trait anger, negative
      affectivity, and biological sex) and situational (i.e., injustice, job
      dissatisfaction, interpersonal conflict, situational constraints, and poor
      leadership) factors in explaining interpersonal and organizational aggression?
      Results show that both individual and situational factors predict aggression and
      that the pattern of predictors is target specific. Implications for future
      research are discussed.

PMID- 17227165
TI  - Expectations of obese trainees: how stigmatized trainee characteristics influence
      training effectiveness.
AB  - This study identifies stigma as a potential precursor to self-fulfilling
      prophecies in training interactions. Expectations held by leaders often result in
      actions that elicit expectancy-confirming behaviors from their subordinates. The
      results of the present study suggest that trainee weight (manipulated with a
      photograph depicting the trainee as either obese or average weight for height)
      influenced female trainer expectations and evaluations of the training and
      trainee. Furthermore, the results suggest that negative expectations held by
      trainers were related to trainee evaluations of the training and the trainer and,
      for less flexible trainers, to decrements in trainee performance on the trained
      task. Overall, the results suggest that trainer expectations can be influenced by
      stereotypes held about trainee characteristics, thus undermining training
      effectiveness.

PMID- 17227166
TI  - An extension of uncertainty management theory to the self: the relationship
      between justice, social comparison orientation, and antisocial work behaviors.
AB  - A multisource field study of 103 employees and their supervisors tested an
      extension of uncertainty management theory (E. A. Lind & K. Van den Bos, 2002; K.
      Van den Bos & E. A. Lind, 2002). According to this theory, persons high in social
      comparison orientation (F. X. Gibbons & B. P. Buunk, 1999) experience chronic
      uncertainty about the self. It was hypothesized that this should strengthen the
      effects of interactional and procedural justice perceptions on antisocial work
      behaviors. As predicted, the negative relationship between employee perceptions
      of interactional justice and supervisory ratings of antisocial work behaviors was
      stronger for people who are high as compared with low in social comparison
      orientation. Results provide evidence for an extension of uncertainty management
      theory to the self-domain.

PMID- 17227167
TI  - Majority and minority influence in group negotiation: the moderating effects of
      social motivation and decision rules.
AB  - In organizational groups, often a majority has aligned preferences that oppose
      those of a minority. Although such situations may give rise to majority
      coalitions that exclude the minority or to minorities blocking unfavorable
      agreements, structural and motivational factors may stimulate groups to engage in
      integrative negotiation, leading to collectively beneficial agreements. An
      experiment with 97 3-person groups was designed to test hypotheses about the
      interactions among decision rule, the majority's social motivation, and the
      minority's social motivation. Results showed that under unanimity rule, minority
      members block decisions, thus harming the group, but only when the minority has
      proself motivation. Under majority rule, majority members coalesce at the
      minority's expense, but only when the majority has a proself motivation.
      Implications for negotiation research and group decision making are discussed.

PMID- 17227168
TI  - Leader-member exchange and citizenship behaviors: a meta-analysis.
AB  - This article provides a meta-analytic review of the relationship between the
      quality of leader-member exchanges (LMX) and citizenship behaviors performed by
      employees. Results based on 50 independent samples (N = 9,324) indicate a
      moderately strong, positive relationship between LMX and citizenship behaviors
      (rho = .37). The results also support the moderating role of the target of the
      citizenship behaviors on the magnitude of the LMX-citizenship behavior
      relationship. As expected, LMX predicted individual-targeted behaviors more
      strongly than it predicted organizational targeted behaviors (rho = .38 vs. rho =
      .31), and the difference was statistically significant. Whether the LMX and the
      citizenship behavior ratings were provided by the same source or not also
      influenced the magnitude of the correlation between the 2 constructs.

PMID- 17227169
TI  - The impact of political skill on impression management effectiveness.
AB  - In this study, the authors investigated the effect of an individual's political
      skill on the relationships between 5 different impression management tactics
      (intimidation, exemplification, ingratiation, self-promotion, and supplication)
      and supervisor evaluations of performance. To test these relationships, the
      authors used a matched sample of 173 supervisor-subordinate dyads who worked full
      time in a state agency. Findings showed that individuals who used high levels of
      any of the tactics and who were politically skilled achieved more desirable
      supervisor ratings than did those who used the tactics but were not politically
      skilled. Opposite results were found when impression management usage was low.
      That is, individuals who were not politically skilled created a more desirable
      image in their supervisors' eyes than did their politically skilled counterparts
      when they did not use these tactics. Practical and research implications for the
      findings as well as directions for future research are offered.

PMID- 17227170
TI  - If you feel bad, it's unfair: a quantitative synthesis of affect and
      organizational justice perceptions.
AB  - Whereas research interest in both individual affect/temperament and
      organizational justice has grown substantially in recent years, affect's role in
      the perception of organizational justice has received scant attention. Here, the
      authors integrate these literatures and test bivariate relationships between
      state affect (e.g., moods), trait affect (e.g., affectivity), and organizational
      justice variables using meta-analytically aggregated effect sizes. Results
      indicated that state and trait positive and negative affect exhibit statistically
      significant relationships with perceptions of distributive, procedural, and
      interactional justice in the predicted directions, with mean population-level
      correlations ranging in absolute magnitude from M(rho) = .09 to M(rho) = .43.
      Correlations involving state affect generally were larger but not significantly
      different from those involving trait affect. Finally, the authors propose ideas
      for investigations at the primary-study level.

PMID- 17227171
TI  - Black and White women's perspectives on femininity.
AB  - The authors explore how Black and White women view three aspects of normative
      femininity, and whether self-rated femininity is related to feminism. Through
      telephone surveys, a nationally representative sample of women (N=1130) rated
      themselves on feminism and items derived from Collins' (2004) benchmarks of
      femininity: feminine appearance, traits, and traditional gender role ideology.
      Confirmatory factor analysis revealed both groups conceptualized femininity as
      including the same dimensions, although Black women rated themselves higher on
      items related to feminine appearance. Among White women, traditional gender
      ideology was negatively related to feminism; among Black women, wearing feminine
      clothes was positively related to feminism. Results are discussed in terms of
      possibilities for resistance to the hegemonic concept of femininity that both
      groups share.

PMID- 17227172
TI  - Acculturation and depression among Hispanics: the moderating effect of
      intercultural competence.
AB  - In the present study the authors examined the relative contributions of typical
      acculturation indicators, general coping, and intercultural competence in
      predicting depression among 96 Hispanic adults. The results indicated that
      intercultural competence served to moderate the relationship between
      acculturation and depression. The combination of high acculturation and high
      intercultural competence was associated with fewer symptoms. General coping
      accounted for significant amounts of variance in predicting depression, over and
      above traditional acculturation variables alone, suggesting that an active
      problem-solving style was associated with a healthier outcome. The findings are
      discussed within the context of integrating competence-based variables into
      psychological conceptualizations of cultural adaptation and the importance of
      group-specific abilities as potential buffers against negative mental health
      consequences.

PMID- 17227173
TI  - The influence of race and ethnicity on psychiatric diagnoses and clinical
      characteristics of children and adolescents in children's services.
AB  - This study examined the influence of race and ethnicity on psychiatric diagnoses
      and clinical characteristics of 1,189 children and adolescents participating in
      the federally funded Comprehensive Community Mental Health Services for Children
      and Their Families Program. Results showed that after controlling for age,
      gender, functional impairment, and socioeconomic status, there were significant
      race and ethnicity effects on diagnosis and clinical characteristics. Black and
      Native Hawaiian youth were more likely than White youth to be diagnosed with
      disruptive behavioral disorders. Hispanic and Native Hawaiian youth were less
      likely than White youth to be diagnosed with depression or dysthymia. Black,
      Asian American, and Native Hawaiian youth were rated as exhibiting less
      internalizing behavior problems than White youth. Implications for research,
      practice, and policy are discussed.

PMID- 17227174
TI  - The stage-specific role of spirituality among African American Christian women
      throughout the breast cancer experience.
AB  - This study presents the results of semistructured interviews conducted with 18
      African American Christian women regarding the role of spirituality throughout
      their breast cancer experiences. The spiritual themes relevant for phases of the
      breast cancer experience are identified. Analysis resulted in the identification
      of 11 codes and 5 subcodes that corresponded to the diagnosis, treatment, and
      posttreatment phases of the breast cancer experience. Most of the survivors
      indicated that their spirituality and faith assisted them throughout the breast
      cancer experience. Discussion focuses on the spiritual resources used by the
      participants at the different stages in the breast cancer experience. Attention
      is given to implications for how professionals can use these resources to assist
      African American women coping with breast cancer.

PMID- 17227175
TI  - Ethnic variation in depressive symptoms in a community sample in Hawaii.
AB  - A modified CES-D was administered to a community sample of 176 European Americans
      (EA), 209 Native Hawaiians (NH), and 357 Japanese Americans (JA), yielding
      measures of depression, positive affect, depressed affect, somatic disturbance,
      and disturbed interpersonal relations. Positive affect was lower in JA relative
      to EA, consistent with findings among Native Japanese, a pattern attributed to
      cultural variation in emotion regulation. NH reported lower positive affect than
      EA, accompanied by elevated negative affect and somatic disturbance, suggesting
      generally higher levels of depressive symptoms. The three ethnic groups varied in
      mental health care usage with differing associations between depressive symptoms
      and experiences of stressful life events. Taken together, these results suggest
      ethnic variation in depressive symptoms may arise from differing cultural
      beliefs.

PMID- 17227176
TI  - Teasing, acculturation, and cultural conflict: psychosocial correlates of body
      image and eating attitudes among South Asian women.
AB  - The current study examined sociocultural correlates of body dissatisfaction and
      maladaptive eating attitudes among 74 South Asian American women. Participants
      completed measures assessing three forms of teasing--general appearance,
      weight/shape, and ethnic--as well as thin-ideal internalization, acculturation,
      cultural conflict, body dissatisfaction, and maladaptive eating attitudes.
      Results indicated that all three types of teasing and cultural conflict were
      significantly related to body dissatisfaction and maladaptive eating attitudes.
      Cultural conflict was found to mediate the relationship between ethnic teasing
      and body dissatisfaction. Neither thin-ideal internalization nor acculturation
      was significantly associated with either body dissatisfaction or maladaptive
      eating attitudes. However, body dissatisfaction was found to mediate the
      relationship between weight/shape teasing and maladaptive eating attitudes.
      Implications of these findings and possible future directions for research on
      South Asian American women are discussed.

PMID- 17227177
TI  - A pilot investigation of the effects of stress on neuropsychological performance
      in Asian-Indians in the United States.
AB  - The present study evaluated the effects of stress and the ethnicity of the
      examiner on neuropsychological performance in a sample of Asian-Indian males in
      the United States. Participants were 60 Asian-Indian college students randomly
      assigned to one of four conditions in a 2 x 2 factorial design. The first factor
      was level of stress induction and the second was ethnicity of examiners. Results
      suggested that both stress inducing instructions and examiner ethnicity impacted
      highly demanding tasks, while moderately difficult tasks were less sensitive to
      ethnicity of the examiner. Results also indicate that examiners should recognize
      the potential impact of ethnicity and heightened level of stress when
      administering and interpreting neuropsychological measures.

PMID- 17227178
TI  - Racism experiences and psychological functioning in African American college
      freshmen: is racial socialization a buffer?
AB  - Previous research has documented the negative effects of racism on the
      psychological health of African Americans. However, consideration of racial
      socialization as a potential buffer against racism experiences has received
      limited attention. The present study investigated whether two types of parental
      racial socialization messages reduced the impact of racism on psychological
      functioning in a sample of 247 African American college freshmen (M=18.30).
      Results indicated that students who reported more racism experiences also had
      poorer levels of psychological functioning as indicated by higher levels of
      psychological stress and psychological distress. Parental messages emphasizing
      the use of African American cultural resources to cope with racism reduced the
      impact of racism on psychological stress only. Cultural pride messages predicted
      less psychological distress while messages emphasizing the use of cultural
      resources predicted greater psychological distress. However, neither message type
      moderated the relationship between racism experiences and psychological distress.
      These results suggest that racial socialization messages have complex relations
      to psychological functioning in African American college students.

PMID- 17227179
TI  - Racial microaggressions and the Asian American experience.
AB  - Racial microaggressions were examined through a focus group analysis of 10 self
      identified Asian American participants using a semistructured interview and brief
      demographic questionnaire. Results identified 8 major microaggressive themes
      directed toward this group: (a) alien in own land, (b) ascription of
      intelligence, (c) exoticization of Asian women, (d) invalidation of interethnic
      differences, (e) denial of racial reality, (f) pathologizing cultural
      values/communication styles, (g) second class citizenship, and (h) invisibility.
      A ninth category, "undeveloped incidents/responses" was used to categorize
      microaggressions that were mentioned by only a few members. There were strong
      indications that the types of subtle racism directed at Asian Americans may be
      qualitatively and quantitatively different from other marginalized groups.
      Implications are discussed.

PMID- 17227180
TI  - Representing word meaning and order information in a composite holographic
      lexicon.
AB  - The authors present a computational model that builds a holographic lexicon
      representing both word meaning and word order from unsupervised experience with
      natural language. The model uses simple convolution and superposition mechanisms
      (cf. B. B. Murdock, 1982) to learn distributed holographic representations for
      words. The structure of the resulting lexicon can account for empirical data from
      classic experiments studying semantic typicality, categorization, priming, and
      semantic constraint in sentence completions. Furthermore, order information can
      be retrieved from the holographic representations, allowing the model to account
      for limited word transitions without the need for built-in transition rules. The
      model demonstrates that a broad range of psychological data can be accounted for
      directly from the structure of lexical representations learned in this way,
      without the need for complexity to be built into either the processing mechanisms
      or the representations. The holographic representations are an appropriate
      knowledge representation to be used by higher order models of language
      comprehension, relieving the complexity required at the higher level.

PMID- 17227181
TI  - The simultaneous type, serial token model of temporal attention and working
      memory.
AB  - A detailed description of the simultaneous type, serial token (ST2) model is
      presented. ST2 is a model of temporal attention and working memory that
      encapsulates 5 principles: (a) M. M. Chun and M. C. Potter's (1995) 2-stage
      model, (b) a Stage 1 salience filter, (c) N. G. Kanwisher's (1987, 1991) types
      tokens distinction, (d) a transient attentional enhancement, and (e) a mechanism
      for associating types with tokens called the binding pool. The authors
      instantiate this theoretical position in a connectionist implementation, called
      neural-ST2, which they illustrate by modeling temporal attention results focused
      on the attentional blink (AB). They demonstrate that the ST2 model explains a
      spectrum of AB findings. Furthermore, they highlight a number of new temporal
      attention predictions arising from the ST2 theory, which are tested in a series
      of behavioral experiments. Finally, the authors review major AB models and
      theories and compare them with ST2.

PMID- 17227182
TI  - Parallel and serial processes in visual search.
AB  - A long-standing issue in the study of how people acquire visual information
      centers around the scheduling and deployment of attentional resources: Is the
      process serial, or is it parallel? A substantial empirical effort has been
      dedicated to resolving this issue (e.g., J. M. Wolfe, 1998a, 1998b). However, the
      results remain largely inconclusive because the methodologies that have
      historically been used cannot make the necessary distinctions (J. Palmer, 1995;
      J. T. Townsend, 1972, 1974, 1990). In this article, the authors develop a
      rigorous procedure for deciding the scheduling problem in visual search by making
      improvements in both search methodology and data interpretation. The search
      method, originally used by A. H. C. van der Heijden (1975), generalizes the
      traditional single-target methodology by permitting multiple targets. Reaction
      times and error rates from 29 representative search studies were analyzed using
      Monte Carlo simulation. Parallel and serial models of attention were defined by
      coupling the appropriate sequential sampling algorithms to realistic constraints
      on decision making. The authors found that although most searches are conducted
      by a parallel limited-capacity process, there is a distinguishable search class
      that is serial.

PMID- 17227183
TI  - The nature of individual differences in working memory capacity: active
      maintenance in primary memory and controlled search from secondary memory.
AB  - Studies examining individual differences in working memory capacity have
      suggested that individuals with low working memory capacities demonstrate
      impaired performance on a variety of attention and memory tasks compared with
      individuals with high working memory capacities. This working memory limitation
      can be conceived of as arising from 2 components: a dynamic attention component
      (primary memory) and a probabilistic cue-dependent search component (secondary
      memory). This framework is used to examine previous individual differences
      studies of working memory capacity, and new evidence is examined on the basis of
      predictions of the framework to performance on immediate free recall. It is
      suggested that individual differences in working memory capacity are partially
      due to the ability to maintain information accessible in primary memory and the
      ability to search for information from secondary memory.

PMID- 17227184
TI  - Where (who) are collectives in collectivism? Toward conceptual clarification of
      individualism and collectivism.
AB  - In psychological research on cultural differences, the distinction between
      individualism and collectivism has received the lion's share of attention as a
      fundamental dimension of cultural variation. In recent years, however, these
      constructs have been criticized as being ill-defined and "a catchall" to
      represent all forms of cultural differences. The authors argue that there is a
      conceptual confusion about the meaning of ingroups that constitute the target of
      collectivism. Collectives are rarely referred to in existing measures to assess
      collectivism. Instead, networks of interpersonal relationships dominate the
      operational definition of "ingroups" in these measures. Results from a content
      analysis of existing scales support this observation. To clarify and expand the
      individualism-collectivism distinction, a theoretical framework is proposed that
      draws on M. B. Brewer and G. Gardner's (1996) conceptualization of individual,
      relational, and collective selves and their manifestation in self
      representations, beliefs, and values. Analyses of data from past studies provide
      preliminary support for this conceptual model. The authors propose that this new
      theoretical framework will contribute conceptual clarity to interpretation of
      past research on individualism and collectivism and guide future research on
      these important constructs.

PMID- 17227185
TI  - Dual-process theory and signal-detection theory of recognition memory.
AB  - Two influential models of recognition memory, the unequal-variance signal
      detection model and a dual-process threshold/detection model, accurately describe
      the receiver operating characteristic, but only the latter model can provide
      estimates of recollection and familiarity. Such estimates often accord with those
      provided by the remember-know procedure, and both methods are now widely used in
      the neuroscience literature to identify the brain correlates of recollection and
      familiarity. However, in recent years, a substantial literature has accumulated
      directly contrasting the signal-detection model against the threshold/detection
      model, and that literature is almost unanimous in its endorsement of signal
      detection theory. A dual-process version of signal-detection theory implies that
      individual recognition decisions are not process pure, and it suggests new ways
      to investigate the brain correlates of recognition memory.

PMID- 17227186
TI  - Adaptive learning and risk taking.
AB  - Humans and animals learn from experience by reducing the probability of sampling
      alternatives with poor past outcomes. Using simulations, J. G. March (1996)
      illustrated how such adaptive sampling could lead to risk-averse as well as risk
      seeking behavior. In this article, the author develops a formal theory of how
      adaptive sampling influences risk taking. He shows that a risk-neutral decision
      maker may learn to prefer a sure thing to an uncertain alternative with identical
      expected value and a symmetric distribution, even if the decision maker follows
      an optimal policy of learning. If the distribution of the uncertain alternative
      is negatively skewed, risk-seeking behavior can emerge. Consistent with recent
      experiments, the model implies that information about foregone payoffs increases
      risk taking.

PMID- 17227187
TI  - Moving beyond pure signal-detection models: comment on Wixted (2007).
AB  - The dual-process signal-detection (DPSD) model assumes that recognition memory is
      based on recollection of qualitative information or on a signal-detection-based
      familiarity process. The model has proven useful for understanding results from a
      wide range of memory research, including behavioral, neuropsychological,
      electrophysiological, and neuroimaging studies. However, a number of concerns
      have been raised about the model over the years, and it has been suggested that
      an unequal-variance signal-detection (UVSD) model that incorporates separate
      recollection and familiarity processes (J. T. Wixted, 2007) may provide an
      equally good, or even better, account of the data. In this article, the authors
      show that the results of studies that differentiate these models support the
      predictions of the DPSD model and indicate that recognition does not reflect the
      summing of 2 signal-detection processes, as the new UVSD model assumes. In
      addition, the assumptions of the DPSD model are clarified in order to address
      some of the common misconceptions about the model. Although important challenges
      remain, hybrid models such as this provide a more useful framework within which
      to understand human memory than do pure signal-detection models.

PMID- 17227190
TI  - Stimulus-outcome interactions during instrumental discrimination learning by rats
      and humans.
AB  - The associative structure mediating goal-directed action was investigated using
      congruent and incongruent conditional discriminations. The stimulus was the same
      as the outcome in each component of the congruent discriminations, whereas the
      stimulus of one component of the incongruent discriminations was the same as the
      outcome of the other component. Humans, but not rats, learned the congruent
      discrimination more rapidly than the incongruent discrimination, a difference
      that the authors attribute to the fact that outcome-response associations caused
      response conflict in the incongruent discrimination. Moreover, responding was
      resistant to outcome devaluation following incongruent, but not congruent,
      training, suggesting that both humans and rats adopted a stimulus-response
      strategy to resolve the incongruent discrimination.

PMID- 17227191
TI  - Preference for symmetry is experience dependent in newborn chicks (Gallus
      gallus).
AB  - Spontaneous pecking preferences toward symmetric or asymmetric stimuli were
      tested in newborn chicks (Gallus gallus). A preference for asymmetric patterns
      was found in naive chicks (either 24 or 48 hours old), although a preference for
      symmetry appeared at retest after chicks had experienced standard rearing
      conditions (Experiments 1 and 2). Only food-experienced chicks preferred
      symmetric patterns; food-deprived and hand-fed chicks did not show any preference
      (Experiment 3). A key factor that allowed for the emergence of a preference for
      symmetry may relate to the improving of pecking sensorimotor skills occurring
      during active food manipulation. Possible explanations are discussed for the late
      emergence of the preference for symmetry and for the preference for asymmetry
      found in naive chicks.

PMID- 17227192
TI  - Rudimental numerical competence in 5-day-old domestic chicks (Gallus gallus):
      identification of ordinal position.
AB  - Numerical competencies were investigated for the 1st time in very young nonhuman
      animals. Chicks (Gallus gallus) learned to identify the 3rd, 4th, or 6th
      positions in a series of 10 identical positions (Experiment 1). Use of spatial
      information (i.e., distances) was ruled out in Experiment 2 (chicks generalized
      the reinforced response to an array of stimuli rotated by 90 degrees as compared
      with training) and Experiment 3 (chicks generalized their response to a series in
      which distances between the single positions had been manipulated). Chicks found
      the correct position even when both identity and distance of each position
      changed from trial to trial (Experiment 4). Overall, young chicks seemed to use
      ordinality when required to identify a target by its numerical serial position.

PMID- 17227193
TI  - How much does number matter to a monkey (Macaca mulatta)?
AB  - Although many animal species can represent numerical values, little is known
      about how salient number is relative to other object properties for nonhuman
      animals. In one hypothesis, researchers propose that animals represent number
      only as a last resort, when no other properties differentiate stimuli. An
      alternative hypothesis is that animals automatically, spontaneously, and
      routinely represent the numerical attributes of their environments. The authors
      compared the influence of number versus that of shape, color, and surface area on
      rhesus monkeys' (Macaca mulatta) decisions by testing them on a matching task
      with more than one correct answer: a numerical match and a nonnumerical (color,
      surface area, or shape) match. The authors also tested whether previous
      laboratory experience with numerical discrimination influenced a monkey's
      propensity to represent number. Contrary to the last-resort hypothesis, all
      monkeys based their decisions on numerical value when the numerical ratio was
      favorable.

PMID- 17227194
TI  - Rhesus monkeys (Macaca mulatta) enumerate large and small sequentially presented
      sets of items using analog numerical representations.
AB  - Two rhesus monkeys selected the larger of two sequentially presented sets of
      items on a computer monitor. In Experiment 1, performance was related to the
      ratio of set sizes, and the monkeys discriminated between sets with up to 10
      items. Performance was not disrupted when 1 set had fewer than 4 items and 1 set
      had more than 4 items, a critical trial type for differentiating object file and
      analog models of numerical representation. Experiment 2 controlled the interitem
      rate of presentation. Experiment 3 included some trials on which number and
      amount (visual surface area) offered conflicting cues. Experiment 4 varied the
      total duration of set presentation and the duration of item visibility. In all of
      the experiments, performance remained high, although total set presentation
      duration also acted as a partial cue for the monkeys. Overall, the data indicated
      that rhesus monkeys estimate the approximate number of items in sequentially
      presented sets and that they are not relying solely on nonnumerical cues such as
      rate, duration, or cumulative amount.

PMID- 17227195
TI  - Disconnect in concept learning by rhesus monkeys (Macaca mulatta): judgment of
      relations and relations-between-relations.
AB  - The authors investigated the role that entropy measures, discriminative cues, and
      symbolic knowledge play for rhesus monkeys (Macaca mulatta) in the acquisition of
      the concepts of same and different for use in a computerized relational matching
      to-sample task. After repeatedly failing to perceive relations between pairs of
      stimuli in a 2-choice discrimination paradigm, monkeys rapidly learned to
      discriminate between 8-element arrays. Subsequent tests with smaller arrays,
      however, suggested that, although important for the initial acquisition of the
      concept, entropy is not a variable on which monkeys are dependent. Not only do
      monkeys choose a corresponding relational pair in the presence of a cue, but they
      also choose the cue itself in the presence of the relational pair--in essence,
      labeling those relations. Subsequent failure in the judgment of relations-between
      relations, however, suggests that perhaps a qualitatively different cognitive
      component exists that prevents monkeys from behaving analogically.

PMID- 17227196
TI  - The role of similarity in human associative learning.
AB  - In 2 experiments, humans received sequences of patterns that were similar (AX-
      >BX, AY-->BY, AZ-->BZ) or dissimilar (CX-->DY, CY-->DZ, CZ-->DX). The patterns
      were portrayed as bugs that could be eliminated with 2 insecticide sprays (red or
      blue). Either spray eliminated bugs with Features A and C, and participants
      learned by trial and error to use one spray (e.g., red) to eliminate bugs with
      Feature B and the other spray (e.g., blue) to eliminate those with Feature D. In
      Experiment 1, participants' spray choice for bugs with Feature A came to match
      that used to eliminate bugs with Feature B, but there was no such associative
      transfer between Features C and D. That is, similarity promoted associative
      transfer of responding between paired patterns when the features used to
      manipulate similarity (i.e., X, Y, and Z) were irrelevant. In Experiment 2, in
      which X, Y, and Z were relevant to the solution of configural discrimination,
      similarity hindered such associative transfer. These results complement those
      found in pigeons (R. A. Rescorla & D. J. Gillan, 1980) and indicate that
      similarity should not be accorded independent status as a principle of
      associative learning.

PMID- 17227197
TI  - The feature positive effect in the face of variability: novelty as a feature.
AB  - Past literature has shown, across various methods and species, that feature
      positive (FP) tasks (AB-/B+) are learned more easily than are feature negative
      (FN) tasks (AB-/B+), giving rise to what is known as the feature positive effect
      (FPE). Experiment 1 was intended to assess the role of expected absence in the
      FPE through manipulation of the context (constant vs. varied common elements)
      that was paired with the feature. The results indicate that novel contextual
      elements (varied common elements) may be salient enough to eliminate the FPE,
      creating a feature negative effect (FNE). Experiment 2 replicated the FNE. The
      addition of a testing phase confirmed that participants in the FN task judged
      novel stimuli to be strong positive predictors whereas participants in the FP
      task did not, thus producing a novelty FPE. These results are problematic for
      contemporary associative learning models.

PMID- 17227198
TI  - Reassembling our view of vulnerable populations.

PMID- 17227199
TI  - Transition to Medicare Part D: an early snapshot of barriers experienced by
      younger dual eligibles with disabilities.
AB  - OBJECTIVE: This study assessed the impact of transition from Medicaid drug
      coverage to Medicare Part D on a sample of dually eligible adults younger than
      age 65 years with disabilities. STUDY DESIGN: Telephone survey of employed adults
      participating in the Kansas Medicaid Buy-In program, Working Healthy, about their
      experiences in accessing medications after their transition to Part D. METHODS: A
      total of 328 (55%) individuals from a random sample of 600 agreed to participate
      in a survey administered by a university-based research unit during February and
      March 2006, which included 18 questions with yes/no, multiple choice, and open
      ended responses. Participants resembled other Kansas dual eligibles
      demographically and medically, other than having slightly higher rates of mental
      illness and lower rates of mental retardation and some physical conditions.
      Participants' 2004 Medicare and Medicaid claims data were analyzed to obtain an
      overview of their comorbidities and previous prescription use. RESULTS: Twenty
      percent of participants reported difficulty obtaining medications, including
      drugs in Part D-protected classes; 13% were required to switch medications; and
      8% stopped taking at least 1 medication. More than half did not know they could
      change plans monthly, potentially improving their access to medications.
      CONCLUSION: The high incidence of access problems despite Centers for Medicare &
      Medicaid Services (CMS) safeguards points to the need for ongoing monitoring of
      Part D. If the problems persist, CMS must be willing to modify the program and/or
      better enforce the rules already in place to avoid adverse outcomes for
      beneficiaries with disabilities.

PMID- 17227200
TI  - Productivity enhancement for primary care providers using multicondition care
      management.
AB  - OBJECTIVE: To assess the impact of a multicondition care management system on
      primary care physician efficiency and productivity. STUDY DESIGN: Retrospective
      controlled repeated-measures design comparing physician productivity with the
      proportion of patients in the care management system. METHODS: The setting was
      primary care clinics in Intermountain Healthcare, a large integrated delivery
      network. The care management system consisted of a trained team with nurses as
      care managers and specialized information technology. We defined the use of the
      care management system as a proportion of referrals by the physician to the care
      manager. Clinic, physician, and patient panel demographics were used to adjust
      expected visit productivity and were included in a multivariate mixed model with
      repeated measures comprising work relative value units and system use. RESULTS:
      The productivity of 120 physicians in 7 intervention clinics and 14 control
      clinics was compared during 24 months. Clinic, physician, and patient panel
      characteristics exhibited similar characteristics, although patients in
      intervention clinics were less likely to be married. Adjusted work relative value
      units were 8% (range, 5%-12%) higher for intervention clinics vs control clinics.
      Additional annual revenue was estimated at 99,986 dollars per clinic. These
      additional revenues outweighed the estimated cost of the program of 92,077
      dollars. CONCLUSIONS: Physician productivity increased when more than 2% of
      patients were seen by a care management team; the increased revenue in our market
      exceeded the cost of the program. Implications for the creation, structure, and
      reimbursement of such teams are discussed.

PMID- 17227201
TI  - Computerized indicators of potential drug-related emergency department and
      hospital admissions.
AB  - OBJECTIVES: To computerize indicators of potential drug-related emergency
      department and hospital admissions and to report the incidence of these potential
      drug-related morbidities for a managed care organization. STUDY DESIGN:
      Retrospective review of healthcare organizations' pharmacy and administrative
      claims databases. METHODS: Thirty-nine indicators were coded and were used in an
      automated search of claims data. The indicators of potential drug-related
      morbidities comprised a pattern of care and an associated adverse outcome.
      Poisson distribution regression analysis was performed to assess the association
      of patient factors with indicator positives. RESULTS: The incidence densities for
      indicator positives were 1.96 (95% confidence interval, 1.60-2.40) per 1000
      patient-years in the general population and 13.6 (95% confidence interval, 8.8
      20.2) per 1000 patient-years among older persons. Age, male sex, number of
      medical conditions, and number of medications from different classes were
      associated with an increased rate of indicator positives. CONCLUSIONS: Indicators
      of potential drug-related morbidities can be fully automated and used to search
      through medical and pharmacy claims. The indicators investigated in this study
      show promise as a quality improvement tool and should be further developed and
      evaluated.

PMID- 17227202
TI  - Practice patterns for managing Helicobacter pylori infection and upper
      gastrointestinal symptoms.
AB  - OBJECTIVE: To assess adherence with guidelines for testing and treatment of
      Helicobacter pylori infection and upper gastrointestinal symptoms. STUDY DESIGN:
      Retrospective longitudinal cohort analysis of patient-level medical and pharmacy
      claims from 75 US managed care plans. METHODS: Persons with new claims for
      antisecretory medication, H pylori tests, or endoscopies were selected from among
      2 million plan members continuously enrolled from 2001 to 2004 and were grouped
      by initial clinical diagnosis (3456 with peptic ulcer disease [PUD], 14,593 with
      nonulcer dyspepsia [NUD], and 36,233 with gastroesophageal reflux disease
      [GERD]). Diagnostic procedures, medications received, and sequencing of specific
      procedures and medications were examined relative to published guidelines by
      initial diagnosis, age, and physician specialty. RESULTS: While guidelines
      recommend testing before treatment, one third of persons receiving antibiotics
      for H pylori infection had not first been tested for the infection. In one third
      of all posttreatment testing, primary care practitioners incorrectly used
      serologic tests, despite their inability to distinguish cured from active
      infection. Eighteen percent of patients with GERD were tested for H pylori,
      although there is no causal link between them. Only two thirds of patients aged
      50 to 64 years with presumed PUD underwent endoscopy, which guidelines recommend
      for older adults; yet one third of patients with PUD aged 18 to 49 years, for
      whom prompt endoscopy is generally not recommended, had an endoscopy within 30
      days of their index date. CONCLUSIONS: Substantial noncompliance with widely
      disseminated guidelines calls for better understanding of appropriate indications
      for H pylori testing and endoscopy to improve patient care and conserve
      healthcare resources.

PMID- 17227203
TI  - Efforts to reduce racial disparities in Medicare managed care must consider the
      disproportionate effects of geography.
AB  - OBJECTIVE: To examine the impact of geographic variation on racial differences in
      7 of 15 Health Plan Employer Data and Information Set (HEDIS) measures that
      assess the quality of the Medicare managed care program (also known as
      Medicare+Choice). STUDY DESIGN: Cross-sectional analysis using the 2004
      individual-level HEDIS for Medicare managed care plans and 2003 Medicare
      enrollment and demographic (ie, denominator) data for more than 5.1 million
      Medicare+Choice enrollees. METHODS: Individual-level HEDIS data were linked with
      Medicare enrollment data. Hierarchical generalized linear models were used to
      assess statistical significance of region and race. Direct standardization was
      used to estimate the rate of meeting each HEDIS standard while controlling for
      differences in age and sex. RESULTS: Quality of care for white Medicare+Choice
      enrollees was strongly correlated with the racial composition of the geographic
      area. Except for cholesterol management after an acute cardiac event, between
      region racial variation was consistently greater than within-region racial
      variation. CONCLUSION: Removing within-region racial variation while ignoring
      geographic differences will not equalize the experiences of black and white
      elders. Rather, both racial and geographic components of healthcare quality must
      be addressed if the Medicare managed care program is to provide care of equal
      quality to all elders regardless of race.

PMID- 17227205
TI  - Cysteine at position 217 in the intracellular loop 1 plays a critical role in
      human PTH receptor type 1 membrane translocation and function.
AB  - PTHR1 mutants lacking endogenous cysteines in transmembrane and intracellular
      domains were generated. Mutant receptors were tested for their biological
      activities and mRNA and cell surface expression levels. C217 in intracellular
      loop 1 was determined to play a critical role in cell surface translocation and
      function of the receptor. INTRODUCTION: Elucidating the role of different domains
      of PTH receptor 1 (PTHR1) is essential for understanding the mechanism of ligand
      receptor interactions. Here we present a study directed at determining the
      importance of cysteine residues present in the intracellular and transmembrane
      (TM) domains of the receptor. MATERIALS AND METHODS: Mutant receptors were
      generated by site-directed mutagenesis. Biological activities were characterized
      by adenylyl cyclase and competition binding assays. RT-PCR, ELISA, and
      immunofluorescence microscopy were carried out to determine receptor mRNA and
      protein expression levels. RESULTS: Mutations C460L and C462L in TM7, C568L in
      the C-terminal intracellular domain of the receptor, and removal of C397 in
      intracellular loop (ICL)3 by insertion of cleavage sites for Factor Xa did not
      affect binding affinity of PTH or agonist-induced adenylyl cyclase activity,
      although maximal responses (IC(max) and EC(max)) were decreased. However,
      mutations C217L in ICL1 or both C217L and C568L simultaneously resulted in a
      decrease in binding and loss of adenylyl cyclase activity. RT-PCR results showed
      that the observed changes in binding and activity were not caused by changes in
      mRNA expression. Next, we determined cell surface and total expression of the
      wildtype and mutant receptors by ELISA. We found that mutations of C460/C462 to L
      moderately decreased transfer of receptors to the cell surface. However, mutation
      of C217 to L in the ICL1 drastically reduced cell surface expression.
      Immunofluorescence and confocal microscopy studies confirmed reduced cell surface
      expression of receptors containing the C217L mutation. Similar results were
      obtained when replacing C217 and C460/C462 of the receptor with A instead of L.
      CONCLUSIONS: Our studies indicate that the cysteine at position 217 in ICL1 plays
      a critical role in translocation to the cell surface and biological function of
      PTHR1.

PMID- 17227206
TI  - Occurrence and characterization of carbapenemase-producing Enterobacteriaceae:
      report from the SENTRY Antimicrobial Surveillance Program (2000-2004).
AB  - Emergence and dissemination of Enterobacteriaceae isolates harboring
      carbapenemases in various geographic regions represents a significant threat to
      the management of nosocomial infections. Enterobacteriaceae isolates from the
      SENTRY Antimicrobial Surveillance Program (2000-2004) demonstrating decreased
      susceptibility to imipenem and meropenem (minimum inhibitory concentration [MIC],
      > or =2 mg/L) were evaluated for the production of metallo-beta-lactamases and
      serine carbapenemases using disk approximation and polymerase chain reaction
      (PCR) tests. Carbapenemase-producing strains were epidemiologically typed by
      automated riboprinting and pulsed-field gel electrophoresis (PFGE) to establish
      clonality. Among 37,557 Enterobacteriaceae (5 genus groups) evaluated, 119
      (0.32%) had increased carbapenem MIC values, and a carbapenemase was identified
      in 51 (42.9%) of these strains. KPC-2 and KPC-3 were the most frequently
      occurring carbapenemases (24 isolates, 20.2%) in the United States and were
      detected in Klebsiella spp, Citrobacter spp., Enterobacter spp., and Serratia
      marcescens strains isolated in New York, Arkansas, and Virginia. SME-2-producing
      S. marcescens were isolated in the New York City area, Texas, and Ohio, while NMC
      A was found in one E. cloacae strain from New York. In contrast, metallo-beta
      lactamases were prevalent in Europe. IMP-1-producing E. cloacae (11 isolates)
      were detected in Turkey, while VIM-1-producing strains were found in Italy
      (Enterobacter spp.) and Greece (Klebsiella pneumoniae). Clonal dissemination of
      carbapenemase-producing strains was observed in several medical centers on both
      continents. The occurrence of carbapenemases in various Enterobacteriaceae
      remains rare but appears to be spreading geographically (not in Latin America),
      mainly with metallo-beta-lactamases being found in Mediterranean Europe and KPC
      enzymes in the New York City area.

PMID- 17227207
TI  - Comparison of the proteome of isoniazid-resistant and -susceptible strains of
      Mycobacterium tuberculosis.
AB  - In an effort to determine whether there is a major difference in protein level
      between isoniazid resistant and susceptible Mycobacterium tuberculosis strains,
      the proteins extracted from nine isoniazid (INH) monoresistant M. tuberculosis
      strains, seven isoniazid susceptible M. tuberculosis strains, and M. tuberculosis
      H37Rv, were analyzed by two-dimensional polyacrylamide gel electrophoresis (2D
      PAGE). In all protein spot differences, five protein spots that are upregulated
      in INH-resistant strains were identified as Rv1446c, Rv3028c, Rv0491, Rv2971, and
      Rv2145 by matrix-assisted laser desorption/ionization-time of fight-mass
      spectrometry (MALDI-TOF-MS). Most of these differential proteins are membrane
      proteins, which are known to be rich in potential diagnostic and therapeutic
      protein targets. These results suggest that the differentially expressed proteins
      from INH-resistant strains might be used as potential immunodiagnosis antigens
      and candidate novel drug targets against drug-resistant tuberculosis.

PMID- 17227208
TI  - Emergence of optochin resistance among Streptococcus pneumoniae in Portugal.
AB  - In most clinical microbiology laboratories optochin susceptibility is used in the
      screening and identification of Streptococcus pneumoniae. We report the
      characterization of 32 optochin-resistant S. pneumoniae strains from 10
      laboratories that constituted 3.2% of all isolates recovered in 2005 in 30
      laboratories in Portugal. Resistant isolates consisted of bile-soluble optochin
      susceptible and optochin-resistant subpopulations with identical antimicrobial
      susceptibility patterns, capsular types and pulsed-field gel electrophoresis
      (PFGE) profiles. The most frequent serotypes--1, 19A, 11A, 3, 8, and 15A--were
      all common serotypes present in infection and colonization isolates in the
      country. The PFGE profiles of the 32 isolates corresponded to those of previously
      identified clones and confirmed that the emergence of these strains could not be
      attributed to clonal expansion. Clinical laboratories must be aware that optochin
      resistant pneumococci are presently circulating in the community. Because
      accurate identification of S. pneumoniae is essential for correct diagnosis and
      adequate therapy of patients, we recommend that at least the bile solubility test
      should be routinely performed in cases of suspected pneumococcal etiology, even
      if the isolates are optochin-resistant.

PMID- 17227209
TI  - In vitro activities of voriconazole and five licensed antifungal agents against
      Candida dubliniensis: comparison of CLSI M27-A2, Sensititre YeastOne, disk
      diffusion, and Etest methods.
AB  - We compared the in vitro activity of six antifungal agents against 62 isolates of
      Candida dubliniensis by the Clinical Laboratory Standards Institute (CLSI
      [formerly National Committee for the Clinical Laboratory Standards]) M27-A2,
      Sensititre YeastOne, disk diffusion, and Etest methods and we studied the effect
      of the time of reading. For the azoles, voriconazole was the most potent in vitro
      followed by fluconazole, ketoconazole, and itraconazole. All the isolates were
      susceptible to amphotericin B and flucytosine. The highest rate of resistance was
      obtained against itraconazole with a high number of isolates defined as
      susceptible dose-dependent. At 24 hr, 100% of the isolates were susceptible to
      ketoconazole, amphotericin B, and flucytosine, 98% susceptible to voriconazole
      and fluconazole, and 95% for itraconazole. At 48 hr, 100% of the isolates
      remained susceptible for flucytosine and amphotericin B, 95% for voriconazole,
      93% for fluconazole, 90% for ketoconazole, and 82% for itraconazole. The
      agreement between the CLSI and the other methods was better at 24 than 48 hr.

PMID- 17227210
TI  - Susceptibility of Lactobacillus plantarum strains to six antibiotics and
      definition of new susceptibility-resistance cutoff values.
AB  - The minimum inhibitory concentrations (MICs) of six antibiotics with activity
      against gram-positive bacteria (ampicillin, clindamycin, erythromycin,
      gentamicin, streptomycin, and tetracycline) were determined by microdilution and
      the Etest in 121 Lactobacillus plantarum strains of plant and dairy origin. MIC
      values for all antibiotics varied widely between strains. The analysis of both
      absolute MICs and their distribution was used to define new susceptibility
      resistance cutoff values for all antibiotics, except for streptomycin. Based on
      these new cutoffs, the studied strains were nearly all identified as either
      susceptible (ampicillin, clindamycin, erythromycin, and gentamicin) or
      intrinsically resistant (streptomycin). The exceptions were four strains with
      MICs for tetracycline higher than the cutoff point (64 microg ml(1)); these were
      suspected to harbor acquired resistance determinants.

PMID- 17227211
TI  - Occurrence of extended spectrum beta-lactamases among isolates of
      Enterobacteriaceae from urinary tract infections in southern Italy.
AB  - The present investigation was undertaken to assess the prevalence of extended
      spectrum beta-lactamases (ESbetaLs) among urinary tract infection (UTI) isolates.
      During 4 months in 2004, a total of 650 Enterobacteriaceae strains from UTIs was
      collected by five clinical microbiology laboratories located in southern Italy
      and the beta-lactamase production was investigated. A total of 50 of the 650
      isolates were double-disk positive and suspected of producing an ESbetaL;
      Escherichia coli (36.0%) and Klebsiella pneumoniae (32.0%) were the most common
      species among all ESbetaL producers. Characterization of ESbetaL determinants was
      carried out by the colony blot hybridization method, and polymerase chain
      reaction (PCR) and DNA sequencing in order to identify the presence of bla (TEM),
      bla (SHV), bla (PER), and bla (CTX-M) determinants. The ESbetaL variants found in
      this study were the following: TEM-15, TEM-24, TEM-52, TEM-134, SHV-12, CTX-M-1,
      CTX-M-3, CTX-M-15, and PER-1. As expected, the majority of the isolates were
      found to be susceptible to imipenem (94%), cefepime (54%) and piperacillin
      tazobactam (54%). The results of this survey show the prevalence of ESbetaL
      enzymes among enterobacterial pathogens causing UTIs in southern Italy.

PMID- 17227212
TI  - Prevalence of aminoglycoside-modifying enzymes genes among isolates of
      Enterococcus faecalis and Enterococcus faecium in Iran.
AB  - Disks containing 120 microg of gentamicin were used to detect high-level
      gentamicin-resistant phenotype (HLGR) among isolates of Enterococcus faecalis (n
      = 79) and E. faecium (n = 35). These isolates were collected from three hospitals
      in Tehran during 2002-2004. The macrobroth dilution assay was then used to
      determine the minimum inhibitory concentration (MIC) of gentamicin. The
      susceptibility of isolates against amikacin, netilmicin, tobramycin, and
      kanamycin were also determined by Kirby-Bauer method. All isolates were subjected
      to polymerase chain reaction (PCR) assays targeting aminoglycoside modifying
      enzyme (AMEs) genes including aac(6 ')-aph(2 "), aph(2 ")-Ib, aph(2 ")-Ic, aph(2
      ")-Ia, aph(2 ")-Id, aph(3 ')-IIIa, and ant(4 ')-Ia. Fifty-nine isolates (52%)
      showed HLGR phenotype. All isolates with HLGR phenotype and those showing 64 <
      MIC < 500 microg/ml contained aac(6 ')-aph(2 "). The aph(3 ')-IIIa was found in
      61% of the isolates with HLGR phenotypes and in 65% of isolates with MIC < 500.
      Coexistence of aac(6 ')-aph(2 ") and aph(3 ')-IIIa gene among HLGR isolates of E.
      faecalis and E. faecium were 60% and 65%, respectively. The gene aph(2 ")-Ic was
      amplified in two isolates of E. faecium. The results of PCR for aph(2 ")-Id,
      ant(4 ')-Ia and aph(2 ")-Ib genes were negative. The aac(6 ')-aph(2 ") was the
      most frequent gene encoding resistance to gentamicin and other aminoglycosides
      followed by aph(3 ')-IIIa. Isolates lacking these genes were susceptible to all
      aminoglyocosides tested in this study.

PMID- 17227213
TI  - Antimicrobial resistance in nontyphoidal Salmonella from food sources in
      Colombia: evidence for an unusual plasmid-localized class 1 integron in serotypes
      Typhimurium and Anatum.
AB  - Seventy-two isolates representing 18 serotypes recovered from various food
      samples collected in Colombia were tested for antimicrobial susceptibilities. The
      collection was further characterized for extended-spectrum cephalosporin,
      aminoglycoside, and tetracycline resistance markers. Multidrug resistant (MDR)
      isolates were further investigated for class 1 integrons and were evaluated for
      the presence of conjugative plasmids along with a determination of the
      incompatibility group by polymerase chain reaction (PCR). Antibiogram analysis
      showed that the incidence rate of ceftiofur resistance was moderately high (15%).
      A similar level of resistance to neomycin and oxytetracycline (11% and 10%,
      respectively) was also observed. There was a high prevalence of gene cassettes as
      part of one or more class 1 integrons (61%), many of which contained determinants
      that contributed to the resistance profile. Class 1 integrons identified in MDR
      Salmonella enterica serotypes Typhimurium and Anatum isolates were characterized.
      Sequencing identified several incomplete open reading frames (ORFs) as part of a
      gene cassette (bla-( imp-13 ), dfr7, blr1088, and aac8) along with a complete
      gene cassette (bla-(oxa2)) in each case. A mosaic of gene cassettes was identical
      in the two Salmonella serotypes. These integrons were located to a conjugative
      replicon. Plasmid profiling and incompatibility typing identified three plasmids
      belonging to Inc groups A/C, P, and W. Our study highlights the role of
      integrons, contributing to a MDR phenotype that is capable of dissemination to
      other bacteria.

PMID- 17227214
TI  - Antimicrobial resistance in commensal Escherichia coli isolated from muscle foods
      as related to the veterinary use of antimicrobial agents in food-producing
      animals in Austria.
AB  - Controversy exists on veterinary drug application in food animal production and
      the relevance for human health of antimicrobial resistant commensals isolated
      from food. The aim of this study was to analyze antimicrobial resistance in
      Escherichia coli isolated from retail meat of various animal species (including
      wild roe deer) in Austria. Our results were analyzed taking into consideration
      the current practices of Austrian veterinarians with regard to their use of
      antibiotic drugs during pig, poultry, and beef production. Resistant isolates
      were found most often in pork (76%) followed by poultry (63%) and beef (40%). On
      wild deer carcasses purchased from Austrian hunters only one isolate was found to
      be resistant. The latter indicates that antimicrobial resistance is not yet an
      environmental problem in animals living in the wild. The common use of
      tetracyclines in veterinary medication in various animal species is clearly
      reflected in the incidence of antimicrobial resistant isolates in commensal E.
      coli. The intensive use of fluoroquinolones in poultry could explain the high
      numbers of nalidixic acid resistant isolates found on poultry meat. Our findings
      partly explain the impact of veterinary drug application on the resistance
      development of E. coli isolated from meat.

PMID- 17227215
TI  - Cloacal Lactobacillus isolates from broilers often display resistance toward
      tetracycline antibiotics.
AB  - Lactobacillus crispatus, L. reuteri, L. amylovorus, L. gallinarum, and L.
      salivarius subsp. salivarius strains isolated from cloacal swabs of broiler
      chickens derived from 20 different farms in Belgium were tested for
      susceptibility to tetracycline and minocycline. Acquired resistance percentages
      to these antibiotics were extremely high for L. crispatus, L. reuteri, L.
      gallinarum, and L. salivarius subsp. salivarius (75%-100%). L. amylovorus on the
      contrary, displayed lower resistance percentages (25%) toward minocycline and
      tetracycline. In several strains, resistance against the tetracycline antibiotics
      was associated with the presence of the resistance genes tet(K), tet(L), tet(M),
      tet(W), and tet(Z). To our knowledge, this is the first report of tet(Z) in
      lactobacilli and tet(K), tet(L), and tet(W) in lactobacilli identified to species
      level. Our findings strengthen the evidence of intestinal Lactobacillus species
      acting as a pool of antimicrobial resistance genes urging the need for prudent
      use of tetracycline antibiotics in poultry production.

PMID- 17227216
TI  - Correction.

PMID- 17227217
TI  - Fragile external phenotype of modern human proximal femur in comparison with
      medieval bone.
AB  - Proximal femur macroanatomy of 118 medieval and 67 contemporary adults, 84
      contemporary elderly, and 48 contemporary hip fracture cases was evaluated.
      Within approximately 1000 years, the femoral neck axis has become longer, and its
      cross-section has become proportionally smaller and more oval in shape. These
      changes in the present external phenotype alone account for approximately 50%
      higher fall-induced stress compared with the medieval situation. INTRODUCTION:
      Bones, as whole skeletal structures, adapt to mechanical stresses they
      customarily experience. Because the present, mechanized lifestyle apparently
      deprives our skeletons of vigorous, habitual physical exertion, we studied
      whether the proximal femur phenotype has evolved vulnerable to fragility
      fractures by time. MATERIALS AND METHODS: Proximal femur macroanatomy of 118
      medieval and 67 contemporary adults, 84 contemporary elderly, and 48 contemporary
      hip fracture cases was evaluated. Using direct measurements of external bone
      dimensions and geometric properties, we estimated the fall-induced stress as an
      index of hip fragility. RESULTS: Within approximately 1000 years, the femoral
      axis length has become substantially longer (analysis of covariance, body height
      adjusted, p < 0.001), whereas the neck circumference has not increased. The
      macroanatomy was found similar between the contemporary adult and elderly groups.
      In hip fracture cases, however, the femoral axis length was further lengthened (p
      < 0.001), but the circumference was somewhat smaller (p = 0.001). Consequently,
      the estimated fall-induced stress can be approximately 1.5-fold today compared
      with the medieval times (p < 0.001), and the secular trend seemed to be worse in
      women (sex-time interaction, p = 0.001). CONCLUSIONS: The modern, relatively
      slender phenotype of the proximal femur alone seems to increase the fall-induced
      stress considerably, and when this phenotype coincides the osteoporotic,
      internally deteriorated femoral neck structure, fracture risk is imminent. This
      mechanically compromised external phenotype underscores the importance of timely
      strengthening of the skeleton and its regular maintenance throughout life.

PMID- 17227218
TI  - Multicenter blinded analysis of RT-PCR detection methods for paramyxoviruses in
      relation to Paget's disease of bone.
AB  - Conflicting results have been reported on the detection of paramyxovirus
      transcripts in Paget's disease, and a possible explanation is differences in the
      sensitivity of RT-PCR methods for detecting virus. In a blinded study, we found
      no evidence to suggest that laboratories that failed to detect viral transcripts
      had less sensitive RT-PCR assays, and we did not detect measles or distemper
      transcripts in Paget's samples using the most sensitive assays evaluated.
      INTRODUCTION: There is conflicting evidence on the possible role of persistent
      paramyxovirus infection in Paget's disease of bone (PDB). Some workers have
      detected measles virus (MV) or canine distemper virus (CDV) transcripts in cells
      and tissues from patients with PDB, but others have failed to confirm this
      finding. A possible explanation might be differences in the sensitivity of RT-PCR
      methods for detecting virus. Here we performed a blinded comparison of the
      sensitivity of different RT-PCR-based techniques for MV and CDV detection in
      different laboratories and used the most sensitive assays to screen for evidence
      of viral transcripts in bone and blood samples derived from patients with PDB.
      MATERIALS AND METHODS: Participating laboratories analyzed samples spiked with
      known amounts of MV and CDV transcripts and control samples that did not contain
      viral nucleic acids. All analyses were performed on a blinded basis. RESULTS: The
      limit of detection for CDV was 1000 viral transcripts in three laboratories
      (Aberdeen, Belfast, and Liverpool) and 10,000 transcripts in another laboratory
      (Manchester). The limit of detection for MV was 16 transcripts in one laboratory
      (NIBSC), 1000 transcripts in two laboratories (Aberdeen and Belfast), and 10,000
      transcripts in two laboratories (Liverpool and Manchester). An assay previously
      used by a U.S.-based group to detect MV transcripts in PDB had a sensitivity of
      1000 transcripts. One laboratory (Manchester) detected CDV transcripts in a
      negative control and in two samples that had been spiked with MV. None of the
      other laboratories had false-positive results for MV or CDV, and no evidence of
      viral transcripts was found on analysis of 12 PDB samples using the most
      sensitive RT-PCR assays for MV and CDV. CONCLUSIONS: We found that RT-PCR assays
      used by different laboratories differed in their sensitivity to detect CDV and MV
      transcripts but found no evidence to suggest that laboratories that previously
      failed to detect viral transcripts had less sensitive RT-PCR assays than those
      that detected viral transcripts. False-positive results were observed with one
      laboratory, and we failed to detect paramyxovirus transcripts in PDB samples
      using the most sensitive assays evaluated. Our results show that failure of some
      laboratories to detect viral transcripts is unlikely to be caused by problems
      with assay sensitivity and highlight the fact that contamination can be an issue
      when searching for pathogens by sensitive RT-PCR-based techniques.

PMID- 17227219
TI  - Effects of a one-month treatment with PTH(1-34) on bone formation on cancellous,
      endocortical, and periosteal surfaces of the human ilium.
AB  - Using bone histomorphometry, we found that a 1-month treatment with PTH(1-34)
      [hPTH(1-34)] stimulated new bone formation on cancellous, endocortical, and
      periosteal bone surfaces. Enhanced bone formation was associated with an increase
      in osteoblast apoptosis. INTRODUCTION: The precise mechanisms by which hPTH(1-34)
      increases bone mass and improves bone structure are unclear. Using bone
      histomorphometry, we studied the early effects of treating postmenopausal women
      with osteoporosis with hPTH(1-34). MATERIALS AND METHODS: Tetracycline-labeled
      iliac crest bone biopsies were obtained from 27 postmenopausal women with
      osteoporosis who were treated for 1 month with hPTH(1-34), 50 microg daily
      subcutaneously. The results were compared with tetracycline-labeled biopsies from
      a representative control group of 13 postmenopausal women with osteoporosis.
      RESULTS: The bone formation rate on the cancellous and endocortical surfaces was
      higher in hPTH(1-34)-treated women than in control women by factors of 4.5 and
      5.0, respectively. We also showed a 4-fold increase in bone formation rate on the
      periosteal surface, suggesting that hPTH(1-34) has the potential to increase bone
      diameter in humans. On the cancellous and endocortical surfaces, the increased
      bone formation rate was primarily caused by stimulation of formation in ongoing
      remodeling units, with a modest amount of increased formation on previously
      quiescent surfaces. hPTH(1-34)-stimulated bone formation was associated with an
      increase in osteoblast apoptosis, which may reflect enhanced turnover of the
      osteoblast population and may contribute to the anabolic action of hPTH(1-34).
      CONCLUSIONS: These findings provide new insight into the cellular basis by which
      hPTH(1-34) improves cancellous and cortical bone architecture and geometry in
      patients with osteoporosis.

PMID- 17227220
TI  - Breast cancer-associated gene 3 (BCA3) is a novel Rac1-interacting protein.
AB  - BCA3 was identified in a yeast two-hybrid screen as a novel Rac1-interacting
      partner in osteoclasts. BCA3 binds directly to Rac and, in vivo, binds GTP-Rac
      but not GDP-Rac. Perinuclear co-localization of BCA3 and Rac1 is observed in CSF
      1-treated osteoclasts. Overexpression of BCA3 attenuates CSF-1-induced cell
      spreading. We conclude that BCA3 regulates CSF-1-dependent Rac activation.
      INTRODUCTION: Rac1, a ubiquitously expressed GTPase, is a mediator of colony
      stimulating factor 1 (CSF-1)-dependent actin remodeling in osteoclasts. Because
      the role of Rac in osteoclasts has not been fully defined, we undertook a yeast
      two-hybrid screen to identify Rac-interacting partners in these cells. MATERIALS
      AND METHODS: A yeast two-hybrid screen was undertaken using a cDNA library
      prepared from osteoclast-like cells as prey and either native Rac1 or
      constitutively active Rac1 (Q61L) as bait. Radiolabeled breast cancer-associated
      gene 3 (BCA3) protein constructs were generated in vitro using rabbit reticulate
      lysates and used in vitro binding assays with Rac1. In vivo binding was assessed
      using myc-tagged Rac1(Q61L) and HA-tagged BCA3. PBD pull-down assays were used to
      determine if GTP-loaded Rac1 preferentially bound BCA3. Co-localization of Rac1
      and BCA3 in osteoclasts was assessed using confocal immunofluorescence. The
      functional significance of the BCA3-Rac1 interaction was assessed by examining
      the effect of overexpressing BCA3 in RAW 264.7 cells on the subsequent spreading
      response to CSF-1. RESULTS: One of three positive clones from the wildtype Rac1
      screen and all three positive clones from the Rac1(Q61L) screen encoded the same
      protein, BCA3. BCA3 expression in osteoclasts was confirmed by RT-PCR and
      immunocytochemistry. BCA3 bound directly to Rac1 in vitro. Deletional analysis
      indicated that amino acids 76-125 in BCA3 are important for its ability to bind
      Rac. In vivo association of the two proteins was shown by co-immunoprecipitation
      of BCA3 and Rac1. Only GTP-bound-Rac but not GDP-bound Rac could interact with
      BCA3 in vivo. Confocal immunocytochemistry showed perinuclear co-localization of
      BCA3 and Rac1 in CSF-1-treated neonatal rat osteoclasts but not in resting
      osteoclasts. Overexpression of BCA3 markedly attenuated the spreading response to
      CSF-1 in RAW 264.7 cells. CONCLUSIONS: These data establish that BCA3 is a novel
      Rac1-interacting protein and suggest that it may influence the ability of Rac1 to
      remodel the actin cytoskeleton.

PMID- 17227221
TI  - Genetic and environmental determinants of volumetric and areal BMD in multi
      generational families of African ancestry: the Tobago Family Health Study.
AB  - BMD is higher and fracture risk is lower among individuals of African versus
      European descent, but little is known about the genetic architecture of BMD in
      the former group. Heritabilities of areal and volumetric BMD were moderate in our
      large families of African descent but differed for trabecular and cortical BMD.
      INTRODUCTION: Populations of African ancestry have lower osteoporotic fracture
      risk and higher BMD than other ethnic groups. However, there is a paucity of
      information regarding the genetic and environmental influences on bone health
      among populations of African heritage. MATERIALS AND METHODS: We dissected the
      genetic architecture of areal BMD measured by DXA at the proximal femur, lumbar
      spine, and whole body and volumetric BMD measured by pQCT at the distal and
      proximal radius and tibia in 283 women and 188 men > or =18 years of age (mean,
      43 years) from eight multigenerational Afro-Caribbean families (mean family size
      > 50). Using quantitative genetic methods, we estimated the residual heritability
      and the effects of anthropometric, demographic, lifestyle, and medical variables
      on areal and volumetric BMD. RESULTS: Compared with U.S. non-Hispanic blacks and
      whites, areal BMD at the femoral neck was highest in the Afro-Caribbean men and
      women at all ages. Trabecular volumetric BMD decreased linearly with increasing
      age, whereas cortical volumetric BMD did not decrease until age 40-49, especially
      in women. Anthropometric, lifestyle, and medical factors accounted for 12-32% of
      the variation in areal and volumetric BMD, and residual heritabilities (range,
      0.23-0.52) were similar to those reported in other ethnic groups. Heritability of
      cortical BMD was substantially lower than that of areal or trabecular volumetric
      BMD, although the measured covariates accounted for a similar proportion of the
      total phenotypic variation. CONCLUSIONS: Our study is the first comprehensive
      genetic epidemiologic analysis of volumetric BMD measured by QCT and the first
      analysis of these traits in extended families of African descent. Genes account
      for as much or more of the total variation in areal and volumetric BMD than do
      environmental factors, but these effects seem to differ for trabecular and
      cortical bone.

PMID- 17227222
TI  - FGF23 concentrations vary with disease status in autosomal dominant
      hypophosphatemic rickets.
AB  - We measured FGF23 concentrations in subjects with ADHR. FGF23 and serum phosphate
      correlated positively in controls and negatively in subjects with ADHR. Elevated
      FGF23 concentrations were associated with lower phosphate values. The variable
      phenotype in ADHR may be caused by fluctuations in FGF23. INTRODUCTION: Autosomal
      dominant hypophosphatemic rickets (ADHR) is a rare disorder of phosphaturia,
      hypophosphatemia, inappropriately low/normal calcitriol, and
      rickets/osteomalacia. ADHR is caused by mutations in a circulating peptide,
      fibroblast growth factor 23 (FGF23). We present the first report of FGF23
      concentrations in subjects with ADHR. The aim was to test the hypotheses that
      subjects with ADHR have elevated FGF23 concentrations and that FGF23
      concentrations are associated with disease severity. MATERIALS AND METHODS: This
      was an observational study at a tertiary referral center. Subjects were from
      three kindreds with FGF23 mutations causing ADHR (n = 42). Controls were
      participants from these families without mutations (n = 55). Fasting blood and
      urine samples were obtained. Biochemistries were determined, and FGF23
      concentrations were measured using two ELISAs. RESULTS: Three cases are presented
      illustrating activity of disease and FGF23 concentrations. One case shows
      persistent hypophosphatemia and elevation of FGF23 concentrations, whereas
      another shows remission of hypophosphatemia corresponding to a decrease in
      previously elevated FGF23 concentrations. Overall cross-sectional group
      differences were nonsignificant for serum phosphate and FGF23 concentrations. C
      terminal FGF23 concentration in controls was 61.0 +/- 28.6 (SD) RU/ml (median,
      52.5 RU/ml), and in subjects with mutations was 148.8 +/- 374.5 RU/ml (median,
      63.1 RU/ml). Mean intact FGF23 concentration in controls was 44.7 +/- 14.9 pg/ml
      (median, 40.4 pg/ml), and in subjects with mutations was 83.2 +/- 233.0 pg/ml
      (median, 39.0 pg/ml). C-terminal FGF23 concentrations were at least +2 SD in
      10/42(24%), and intact FGF23 concentrations were at least +2 SD in 3/34(9%).
      Phosphate correlated positively with C-terminal and intact FGF23 in both controls
      and in subjects with mutations with phosphate >2.5 mg/dl but correlated
      significantly negatively with C-terminal and intact FGF23 in ADHR subjects with
      phosphate < or =2.5 mg/dl. CONCLUSIONS: Elevated FGF23 concentrations are
      associated with hypophosphatemia in ADHR, and remission of the phenotype is
      associated with lower FGF23 concentrations. FGF23 has an opposite relationship
      with phosphate in ADHR compared with controls. We conclude that ADHR symptoms and
      disease severity likely fluctuate with FGF23 concentrations.

PMID- 17227223
TI  - Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal
      mineralization.
AB  - PHOSPHO1 is a phosphatase highly expressed in bone. We studied its functional
      involvement in mineralization through the use of novel small molecule inhibitors.
      PHOSPHO1 expression was present within matrix vesicles, and inhibition of enzyme
      action caused a decrease in the ability of matrix vesicles to calcify.
      INTRODUCTION: The novel phosphatase, PHOSPHO1, belongs to the haloacid
      dehalogenase superfamily of hydrolases and is capable of cleaving
      phosphoethanolamine (PEA) and phosphocholine to generate inorganic phosphate. Our
      aims in this study were to examine the expression of PHOSPHO1 in murine
      mineralizing cells and matrix vesicles (MV) and to screen a series of small
      molecule PHOSPHO1-specific inhibitors for their ability to pharmacologically
      inhibit the first step of MV-mediated mineralization. MATERIALS AND METHODS: q
      PCR and immunohistochemistry were used to study the expression and localization
      profiles of PHOSPHO1. Inhibitors of PHOSPHO1's PEA hydrolase activity were
      discovered using high-throughput screening of commercially available chemical
      libraries. To asses the efficacy of these inhibitors to inhibit MV
      mineralization, MVs were isolated from TNAP-deficient (Akp2(-/-)) osteoblasts and
      induced to calcify in their presence. RESULTS: q-PCR revealed a 120-fold higher
      level of PHOSPHO1 expression in bone compared with a range of soft tissues. The
      enzyme was immunolocalized to the early hypertrophic chondrocytes of the growth
      plate and to osteoblasts of trabecular surfaces and infilling primary osteons of
      cortical bone. Isolated MVs also contained PHOSPHO1. PEA hydrolase activity was
      observed in sonicated MVs from Akp2(-/-) osteoblasts but not intact MVs.
      Inhibitors to PHOSPHO1 were identified and characterized. Lansoprazole and
      SCH202676 inhibited the mineralization of MVs from Akp2(-/-) osteoblasts by 56.8%
      and 70.7%, respectively. CONCLUSIONS: The results show that PHOSPHO1 localization
      is restricted to mineralizing regions of bone and growth plate and that the
      enzyme present within MVs is in an active state, inhibition of which decreases
      the capacity of MVs to mineralize. These data further support our hypothesis that
      PHOSPHO1 plays a role in the initiation of matrix mineralization.

PMID- 17227224
TI  - Are nonresorbing osteoclasts sources of bone anabolic activity?
AB  - Some osteopetrotic mutations lead to low resorption, increased numbers of
      osteoclasts, and increased bone formation, whereas other osteopetrotic mutations
      lead to low resorption, low numbers of osteoclasts, and decreased bone formation.
      Elaborating on these findings, we discuss the possibility that osteoclasts are
      the source of anabolic signals for osteoblasts. In normal healthy individuals,
      bone formation is coupled to bone resorption in a tight equilibrium. When this
      delicate balance is disturbed, the net result is pathological situations, such as
      osteopetrosis or osteoporosis. Human osteopetrosis, caused by mutations in
      proteins involved in the acidification of the resorption lacuna (ClC-7 or the a3
      V-ATPase), is characterized by decreased resorption in face of normal or even
      increased bone formation. Mouse mutations leading to ablation of osteoclasts
      (e.g., loss of macrophage-colony stimulating factor [M-CSF] or c-fos) lead to
      secondary negative effects on bone formation, in contrast to mutations where bone
      resorption is abrogated with sustained osteoclast numbers, such as the c-src
      mice. These data indicate a central role for osteoclasts, and not necessarily
      their resorptive activity, in the control of bone formation. In this review, we
      consider the balance between bone resorption and bone formation, reviewing novel
      data that have shown that this principle is more complex than originally thought.
      We highlight the distinct possibility that osteoclast function can be divided
      into two more or less separate functions, namely bone resorption and stimulation
      of bone formation. Finally, we describe the likely possibility that bone
      resorption can be attenuated pharmacologically without the undesirable reduction
      in bone formation.

PMID- 17227225
TI  - Mitochondrial-nuclear communications.
AB  - Mitochondria cannot be made de novo but replicate by a mechanism of recruitment
      of new proteins, which are added to preexisting subcompartments. Although
      mitochondria have their own DNA, more than 98% of the total protein complement of
      the organelle is encoded by the nuclear genome. Mitochondrial biogenesis requires
      a coordination of expression of two genomes and therefore cross talk between the
      nucleus and mitochondria. In mammals, regulation of mitochondrial biogenesis and
      proliferation is influenced by external factors, such as nutrients, hormones,
      temperature, exercise, hypoxia, and aging. This complexity points to the
      existence of a coordinated and tightly regulated network connecting different
      pathways. Communications are also required for eliciting mitochondrial responses
      to specific stress pathways. This review covers the mechanisms of mitochondrial
      biogenesis and the way cells respond to external signals to maintain
      mitochondrial function and cellular homeostasis.

PMID- 17227226
TI  - Tetrapyrrole biosynthesis in higher plants.
AB  - Tetrapyrroles play vital roles in various biological processes, including
      photosynthesis and respiration. Higher plants contain four classes of
      tetrapyrroles, namely, chlorophyll, heme, siroheme, and phytochromobilin. All of
      the tetrapyrroles are derived from a common biosynthetic pathway. Here we review
      recent progress in the research of tetrapyrrole biosynthesis from a cellular
      biological view. The progress consists of biochemical, structural, and genetic
      analyses, which contribute to our understanding of how the flow and the synthesis
      of tetrapyrrole molecules are regulated and how the potentially toxic
      intermediates of tetrapyrrole synthesis are maintained at low levels. We also
      describe interactions of tetrapyrrole biosynthesis and other cellular processes
      including the stay-green events, the cell-death program, and the plastid-to
      nucleus signal transduction. Finally, we present several reports on attempts for
      agricultural and horticultural applications in which the tetrapyrrole
      biosynthesis pathway was genetically modified.

PMID- 17227227
TI  - Nuclear factor-kappa B: a transcription factor for all seasons.
AB  - NF-kappaB, first discovered in 1986 in the nucleus of B cells as an
      immunoglobulin-kappa light chain enhancer, is today known as a transcription
      factor that is ubiquitously present in all cell types (not just B cells). It is
      conserved from drosophila to man, resides in the cytoplasm (not nucleus) in the
      resting state and binds to the promoter of > 400 different genes (not just
      immunoglobulin). Both NF-kappaB and TNF are essential components of the immune
      system, with their critical physiological role being in the immune defense.

PMID- 17227228
TI  - NF-kappa B as a therapeutic target in autoimmune disease.
AB  - NF-kappaB transmits signals from the cell surface to the nucleus. Signaling
      through cell surface receptors to activate NF-kappaB and mitogen-activated
      protein kinases through adaptor molecules is of critical importance to survival
      and activation of all cells in the body, including those regulating innate and
      adaptive immunity. As such, NF-kappaB is a key signaling component in
      autoimmunity and an attractive target for autoimmune disease therapy. However,
      given its global importance, targeting NF-kappaB tends to be immunosuppressive.
      In this review, the authors discuss the roles played by NF-kappaB in
      autoimmunity, drugs which target it, and complexities which need to be addressed
      to improve the use of NF-kappaB as a target. Finally, the authors highlight some
      novel approaches that are likely to be important in the next generation of NF
      kappaB therapies.

PMID- 17227229
TI  - NF-kappa B as a therapeutic target in neurodegenerative diseases.
AB  - NF-kappaB is a transcription factor that regulates numerous physiological
      functions, and that is involved in the pathogenesis of various diseases. In the
      nervous system there is evidence supporting a dual role of NF-kappaB in
      neurodegenerative diseases; activation of NF-kappaB in neurons promotes their
      survival, whereas activation in glial and immune cells mediates pathological
      inflammatory processes. The reason for such a dichotomy lies in the complexity of
      the NF-kappaB system. Emerging research has begun to dissect the pathways leading
      to the activation of the different NF-kappaB proteins, and the gene targets of NF
      kappaB, in cells of the nervous system. In this article the authors discuss
      recent findings concerning the roles of NF-kappaB in the pathogenesis of several
      neurodegenerative disorders, and its potential as a pharmaceutical target for
      these disorders.

PMID- 17227230
TI  - NF-kappa B as a target for cancer therapy.
AB  - NF-kappaB transcription factors and the signaling pathways that activate them
      play a critical role in cancer development, progression and therapy, and recently
      have become a focal point for intense drug discovery and development efforts.
      This article presents a critical review on the different types of inhibitors
      targeting the NF-kappaB pathway at several stages.

PMID- 17227231
TI  - Protection of endogenous enkephalin catabolism as natural approach to novel
      analgesic and antidepressant drugs.
AB  - The most efficient drugs to alleviate severe pain are opioid compounds. However,
      their chronic use could be associated with serious drawbacks, such as tolerance,
      respiratory depression and constipation. Therefore, there is a need for compounds
      able to efficiently alleviate inflammatory and neurogenic pain following chronic
      treatment. The discovery that the endogenous opioid peptides, enkephalins, are
      inactivated by two metallopeptidases, neutral endopeptidase and aminopeptidase N,
      which can be blocked by synthetic dual inhibitors, represents a promising way to
      develop 'physiological' analgesics devoid of morphine side effects. These dual
      inhibitors also have antidepressant-like properties through enkephalin-related
      activation of delta-opioid receptors. This is expected to reduce the emotional
      component of pain in humans. This article reviews the promising data obtained for
      future development of a new class of analgesic that could be of major interest in
      a number of severe and chronic pain syndromes.

PMID- 17227232
TI  - Targeting acetylcholinesterase to treat neurodegeneration.
AB  - Neurodegenerative disorders, such as Alzheimer's disease, are often characterised
      by the degeneration of the cholinergic system. Thus, the aim of many treatment
      regimens is to support this system either by means of muscarinic agonists or by
      inhibitors of acetylcholinesterase (AChE), the latter being able to increase the
      concentration of acetylcholine. However, both pharmacological groups of drugs can
      only help in the beginning of the progressive disease. The finding that the
      occupation of the peripheral anionic site of AChE is able to stop the formation
      of the amyloid plaque led to the development of bivalent ligands that occupy both
      the active and the peripheral site. This dual action might be more beneficial for
      treatment of Alzheimer s disease than simple inhibition of the acetylcholine
      hydrolysis. Thus, the new bivalent ligands are the focus of this review.

PMID- 17227233
TI  - MTP inhibition as a treatment for dyslipidaemias: time to deliver or empty
      promises?
AB  - The development of cholesterol-lowering drugs, including a statins, bile acid
      sequestrants and cholesterol absorption inhibitors has expanded the options for
      cardiovascular prevention. Recent treatment guidelines emphasise that individuals
      at substantial risk for atherosclerotic coronary heart disease should meet
      defined lipid targets. Combination therapy with drugs that have different and
      complementary mechanisms of action is often needed to achieve these goals.
      Existing approaches to the treatment of hypercholesterolaemia are still
      ineffective in halting the progression of coronary artery disease in some
      patients despite combination therapies. Other patients are resistant to, or
      intolerant of, conventional pharmacotherapy and remain at high-risk of
      atherosclerotic cardiovascular disease, so that alternative approaches are
      needed. New agents, including inhibitors of microsomal triglyceride transfer
      protein (MTP), may play a future role, either alone or in combination, in the
      treatment of hyperlipidaemias. This review focuses on novel approaches to treat
      dyslipidaemias via the inhibition of MTP. Patients most suitable for use of MTP
      inhibitors include those with hepatic hypersecretion of apoB, including the
      metabolic syndrome, Type 2 diabetes mellitus and familial combined
      hyperlipidaemia, as well as homozygous and heterozygous familial
      hypercholesterolaemia. However, certain safety issues with these agents need
      resolving, particularly fatty liver disease.

PMID- 17227234
TI  - The role of renin-angiotensin system inhibition in the treatment of hypertension
      in metabolic syndrome: are all the angiotensin receptor blockers equal?
AB  - The metabolic syndrome (MetS) is a strong predictor of cardiovascular morbidity
      and mortality, as well as new Type 2 diabetes. MetS consists of visceral obesity,
      elevated blood pressure, impaired glucose metabolism, atherogenic dyslipidaemia
      (elevated triglycerides and low levels of high-density lipoprotein cholesterol),
      as well as other metabolic abnormalities. The underlying pathophysiology seems to
      be largely, but not uniquely, attributable to insulin resistance. Existing
      antihypertensive drugs were designed to lower blood pressure rather than to
      modify the metabolic abnormalities associated with hypertension. This review
      considers the role of renin-angiotensin system inhibition and especially the use
      of angiotensin receptor blockers (ARBs) in the treatment of hypertension in MetS.
      There are differences among ARBs. Among them is the uricosuric effect of
      losartan. Furthermore, telmisartan may function as a partial agonist of the
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma).

PMID- 17227235
TI  - Malignancies of the head and neck: the role for molecular targeted agents.
AB  - Although cancers arising in the head and neck region are a diverse group of
      malignancies, a unifying thread remains a poor overall survival for patients with
      advanced, recurrent or metastatic disease. Treatment strategies need to evolve
      and improve upon established therapeutic practices. As the process of cancer
      evolution is understood to be derived from aberrations in genetic and epigenetic
      processes, molecularly targeted agents offer attractive therapeutic options by
      restoring normal control of oncogenic processes. The direct role for the
      treatment of squamous cell carcinoma of the head and neck, nasopharynx and
      salivary gland carcinomas with these novel, molecularly targeted agents are
      reviewed and their potential to improve on the existing standard of care is
      further explored.

PMID- 17227236
TI  - Is YKL-40 a new therapeutic target in cancer?
AB  - YKL-40 is produced by cancer cells and tumour-associated macrophages. YKL-40 may
      play a role in cancer cell proliferation, differentiation, survival,
      invasiveness, metastasis, in angiogenesis and the inflammation and remodelling of
      the extracellular matrix surrounding the tumour. Serum YKL-40 is a biomarker of
      prognosis, confirmed in 13 different types of cancer including > 2500 patients.
      Highest serum YKL-40 is found in patients with metastatic cancer with the
      shortest recurrence-free interval and shortest overall survival. Serum YKL-40
      provides independent information compared with clinical characteristics and
      biomarkers, such as HER2, carcinoembryonic antigen, CA-125, prostate-specific
      antigen and lactate dehydrogenase. The authors hypothesise that inhibition of YKL
      40 by monoclonal antibodies either directly or towards its receptor may be as
      efficient a cancer therapeutic as the monoclonal antibodies against HER2, HER1,
      vascular endothelial growth factor and CD20. Drugs inhibiting YKL-40 should be
      explored as new cancer therapeutics.

PMID- 17227237
TI  - Targeting serum antibody for cancer diagnosis: a focus on colorectal cancer.
AB  - The ability of the immune system to magnify the appearance of disease by
      generating relatively large amounts of antibody in response to small amounts of
      disease makes it a natural biosensor, and serum antibodies have emerged as
      promising biomarkers for the detection of cancer. This review summarizes recent
      progress in targeting serum antibodies for cancer diagnosis, with a particular
      focus on colorectal cancer (CRC). Several serum antibodies have been detected at
      increased levels in CRC patients, including p53, carcinoembryonic antigen, Ras,
      topoisomerase II-alpha, histone deacetylase 3 and 5, ubiquitin C-terminal
      hydrolase L3, tropomyosin and cyclin B1. As each antibody is only present in a
      limited proportion of patients (usually < 40%), a combination of serum antibodies
      that defines the 'immunological signature' of cancer needs to be developed. High
      throughput methods to identify new serum antibodies for cancer diagnosis are also
      reviewed.

PMID- 17227238
TI  - Recent advances in targeted therapy for non-small cell lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) is characterized by wide molecular
      heterogeneity. In recent years, novel agents that target specific, aberrant
      molecular pathways in NSCLC have been under rigorous evaluation. Erlotinib, an
      inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase,
      improves survival for advanced NSCLC patients who progressed following one or two
      prior chemotherapy regimens. Novel molecular predictive markers, such as EGFR
      mutations and gene amplification, are at present under evaluation to select
      patients for therapy with erlotinib. Another area of progress is the recent
      demonstration that bevacizumab, a monoclonal antibody against the vascular
      endothelial growth factor (VEGF), extended survival when administered in
      combination with chemotherapy for patients with non-squamous NSCLC. Promising
      anticancer activity has also been noted with agents that inhibit the VEGF
      receptor tyrosine kinase in patients with advanced NSCLC. Inhibitors of the
      proteosomal complex, histone deacetylase, mammalian target of rapamycin pathway,
      and other growth factor receptor-mediated signaling are under investigation for
      treatment of NSCLC. These developments have paved the way for a new era of tailor
      made therapies based on clinical or molecular/genetic profiles in the treatment
      of NSCLC. This article reviews the recent advances in targeted therapy of
      advanced NSCLC.

PMID- 17227240
TI  - [Adult dominant polycystic kidney disease: molecular mechanisms and new
      therapeutic possibilities].

PMID- 17227242
TI  - [Recommendations for the use of equations to estimate glomerular filtration rate
      in adults. Spanish Society of Nephrology].

PMID- 17227241
TI  - [Hypoadiponectinemia: a cardiovascular risk factor in uremia. A view from the
      evidence].

PMID- 17227243
TI  - [Molecular diagnosis of adult dominant polycystic kidney disease in the Canary
      Islands].
AB  - Adult dominant polycystic kidney disease is an hereditary condition responsible
      for 6% of end-stage renal failure in Spain. Two genes were located in chromosomes
      16 and 4 as related to this age-dependent disease in the 90s (PKD1 and PKD2). The
      diagnosis can be easily achieved by sonographic study, but molecular analysis by
      means of linkage analysis has the advantage of an early diagnosis in asymptomatic
      genetic carriers, with a view to the preventive follow-up of these subjects and
      genetic counselling. In this paper we present the results of molecular analysis
      of 30 families with Adult Dominant Polycystic Kidney Disease (from the province
      of Las Palmas Spain), carried out linkage analysis with two series of
      microsatellite markers located within or in the vicinity ofPKD1 (D16S521, KG8,
      AC2.5, CW2, SM7) and PKD2 (D4S1538, D4S1534, D4S423,D4S414) genes. The objectives
      of the study were: first, to verify the informativeness, and therefore, the
      usefulness of these markers for family studies in our population; and second,to
      assess the sensitivity and specificity of the genetic analysis in our population.
      Most of the markers showed a high heterozygosity, comparable to data in other
      studies. Considering the alleles of the different markers together in a
      chromosome as an haplotype increased the informativeness of the markers, and
      allowed the unequivocal identification of genetic data in 97.7% of patients and
      88.7% of healthy subjects. The sensitivity and specificity of the genetic
      analysis were 90.7% (CI 95%: 85.7-95.7) and 86.8% (CI 95%: 80.6-93.0),
      respectively.

PMID- 17227244
TI  - [Helicobacter pylori does not contribute to iron deficiency in hemodialysis
      patients].
AB  - BACKGROUND: Many studies in the general population have shown a link between
      Helicobacter pylori infection and iron-deficiency, often resulting in iron
      deficient anaemia. Despite the high prevalence of iron deficiency in hemodialysis
      patients, no studies have been performed in this population. OBJECTIVE: To
      evaluate the role of Helicobacter pylori infection in the appearance of anemia
      and the iron requirements in our hemodialysis population. MATERIAL AND METHODS:
      After excluding patients with severe pathology and short life expectancy and
      those with blood losses secondary to other causes, 79 patients were included.Iron
      requirements and anaemia were determined by iron serum, ferritin, and hematocrit
      values; and by transfusion, eritropoietin and iron requirements. The diagnosis of
      Helicobacter pylori status was established by the concordance of at least two of
      the three non invasive diagnostic methods performed (breath test, serology and
      fecal antigen of Helicobacter pylori). RESULTS: Prevalence of Helicobacter pylori
      infection was 43%. No significant differences between patients infected or not by
      Helicobacter pylori were found in any of the variables analysed: hematocrit
      (33.5% versus 34.1%), serum iron (58.9 versus 63.7 pg/dl), ferritin(340.3 versus
      264.2 ng/ml), transferrin saturation index (22.5% versus 25.2%), dose of
      eritropoietin administered (96.6 versus 93.5 U/kg/weekly), and parenteral iron
      (1,389 versus 1,538 mg/year). A noteworthy finding was that patients with
      Helicobacter pylori infection had been on hemodialysis for a shorter period than
      those without (37.4 versus 63.7 months,p = 0.04). CONCLUSION: Helicobacter pylori
      infection has no effect on anaemia (hematocrit, Eritropoietin dose or iron needs)
      in our hemodialysis patients. Prevalence of Helicobacter pylori is lower in
      patients with longer time on dialysis. We consider that the diagnosis of
      Helicobacter pylori infection must be reserved for clinical peptic ulcer
      suspicion or patients on transplant waiting list.

PMID- 17227245
TI  - [Compliance with the 2002 consensus document of the Spanish Society of Nephrology
      for the control of diabetic nephropathy in Catalonia (ECCODIAB)].
AB  - OBJECTIVE: To evaluate the level of compliance with the 2002 consensus document
      (Spanish Society of Nephrology) on guidelines for the detection, prevention and
      treatment of diabetic nephropathy in Catalonia. SUBJECTS AND METHODS: Multicenter
      (23 hospitals), observational, cross-sectional, descriptive study conducted in
      413 diabetic patients (61.7% men, 38.3% women) with a median age of 66.2 +/-11.5
      years (26-93 years). The ANOVA test (post-hoc analysis; p value< 0.05) was used
      to study the relationships between the stages of diabetic nephropathyand
      different variables. RESULTS: 90.3% of the patients had type 2 DM. The following
      anthropometric parameters were observed: BMI 29.8 +/- 5 kg/m2 (BMI > 30 kg/m2:
      48.7%) and waist circumference 104.1 +/- 14 cm (48.6% men > 102 cm and 78.9%
      women > 88 cm). Serum creatinine 1.9 +/- 1.3 mg/dl and simplified MDRD equation
      45.3 +/- 25.0 ml/min/1.73 m2 [65.8%with CKD stages 3 and 4]. 80% of patients had
      ophthalmologic examination and 52.8% antiplatelet treatment. Hb A1c was 7.3 +/-
      1.3%, but the percentage of patients with glycated hemoglobin > 7% and 8% was
      54.9 and 28.6% [only 50.2% had been seen by an endocrinologist in the last 6
      months]. 52.8% of patients were treated with insulin and 44.1% with anti-diabetic
      drugs, although only 19.6% used the new anti-diabetic drugs. 61% of patients had
      an LDLc > 100 mg/dl (61% treated) and 44% had triglycerides (TG) > 150 mg/dl (72%
      treated). 95% of patients presented with hypertension (BP > or = 130/80 mmHg),91%
      were undergoing antihypertensive treatment (79.7% with angiotensin-converting
      enzyme inhibitors and / or angiotensin receptor blockers). 81% with
      microalbuminuria and 78%with established proteinuria were receiving anti
      proteinuric treatment. Of the patients considered to be refractory to BP (>3
      drugs), only 28.9% underwent ambulatory BP monitoring. Significant differences
      were observed between stages of diabetic nephropathy and glycated hemoglobin
      (HBA1c; p = 0.048), systolic blood pressure (SBP; p = 0.024), lipidic control
      (HDLc; p = 0.015 and TG; p = 0.034), anemia (Hb; p = 0.010) and CKD (creatinine
      and sMDRD; p = 0.000). The levels of compliance with the therapeutic objectives
      regarding lipid control (LDL < or = 100 mg/dl and TG< or = 150 mg/dl), BP < or =
      130/80 mmHg and HbA1c < or =7% were 1 objective: 68%, 2 objectives: 21.8% and 3
      objectives: only 4% of patients. CONCLUSIONS: According to the results of our
      study, only a reduced proportion of patients fulfilled the different therapeutic
      end-points indicated. Future measures will be directed at improving physician
      patient relationships with the main aim of intensifying the therapeutic measures
      to attain better metabolic and blood pressure control, nephroprotection and
      prevention in the appearance of cardiovascular events.

PMID- 17227246
TI  - [Hemodialysis prospective multicentric quality study].
AB  - In medicine a considerable amount of resources are used in research, but very
      little attention is paid to ensuring that the findings of research are
      implemented in routine clinical practice. This prospective study has the aim to
      evaluate the efficiency of some clinical management strategies (feedback,
      benchmarking and improving plans) on haemodialysis treatment results in 4
      different dialysis centres. We collected consensus data related to haemodialysis
      results every 6-8 months and informed each centre about its own results
      (feedback) and how these related to the others(benchmarking). We designed
      improving plans for any bad result detected. By the end of two years of follow
      up, 294 patients had been included in the study. The results obtained at the end
      of the study had improved in comparison with those obtained at the beginning
      (statistically significant) for the following indicators: % of patients with Hb<
      11 g/dl, % patients with Kt/v < 1.2, mean Kt/v, mean albumin, % patients with
      albumin< 3.5 g/dl y % patients with C reactive protein (CRP) > 5 mg/dl. No
      statistical changes were found in: mean erythropoietin (EPO) doses, blood
      pressure (BP), phosphorus plasmatic,calcium-phosphorus product, parathormone
      (PTHi) and vascular access distribution. We explained the absence of any
      improvement because of adequate start indicators in some areas (BP and vascular
      access), therapy with limited efficiency (calcitriol, calcium carbonate and
      others), lack of support resources (dietetic unit) or inadequate
      design/implementation of improving plans.In conclusion, our intervention
      illustrates that combined clinical management strategies(feedback, benchmarking
      and improving plans) are efficiency in improving some areas of haemodialysis
      treatment (anaemia, dialysis dose, nutrition and inflammation), although it does
      not improve calcium phosphate metabolism related indicators.

PMID- 17227247
TI  - [Control of arterial hypertension by means of a regimen of hemodialysis on
      alternate days (HDAA or EODD: "Every Other Day Dialysis") versus 2 conventional
      regiments of 4 and 5 hours per session 3 times a week with 72 hours without
      sessions during the weekends].
AB  - An increase in the frequency of hemodialysis sessions improves control of
      extracellular volume and blood hypertension and consequently reduces the
      mortality related to cardiovascular aetiology in hemodialysis patients.We report
      the evolution of the blood hypertension depending on the need for
      antihypertensive drugs in a group of 38 prevalent patients that were included in
      a every-other-day dialysis schedule (EODD), and compare it with the results in
      two other groups of prevalent patients that were dialyzed in conventional,
      previously employed schedules without week-end sessions 4 hours x 3 x week and 5
      hours x 3 x week. All three groups received hemodialysis treatment for more than
      6 months.A 68% (26/38) of the patients received antihypertensive treatment at the
      beginning the EODD schedule and, after 16 months, only 7.9% (3/38) of them
      required antihypertensive treatment (p < 0.001) with reduction in two of the
      three remanent patients; hypertension control in those 25 patients took an
      average of 100 +/- 15 days. The final frequency of hypertension in EODD was lower
      (p < 0.002) than the frequency registered in the 84 prevalent patients in 4h x 3
      x week schedule, and also lower (p = 0.065) than the frequency of the 56
      prevalent patients in 5h x 3 x week schedule. There is a significant difference
      (p < 0,05) between EODD and 4h x 3 x week schedule as regards average figures of:
      increase in weight, decrease in dry-weight, blood pressure levels and hypotension
      incidence. EODD also produced better results than 5h x 3 x week schedule in this
      regard although statistics did not reflect it. The results using the every-other
      day hemodialysis schedule support previous experiences(Lecce, Columbia) which
      achieved a good control of the dry-weight by means of suppressing the volume
      overload gained during the weekend and consequently obtaining adequate
      ultrafiltration rates and high reduction both of the hypertension and of the
      symptoms of intolerance to hemodialysis, which are so frequent in conventional
      schedules with 72 hours without hemodialysis sessions.

PMID- 17227248
TI  - [Prospective monitoring of vascular access in hemodialysis by means of a
      multidisciplinary team].
AB  - PURPOSE: Nowadays, expert guidelines recommend the monitoring programs of the
      vascular access (VA) by a multidisciplinary team. MATERIAL AND METHOD: We present
      the experience over the last five years, of a prospective VA surveillance by a
      multidisciplinary team. The quality indicators reached are described as the
      associated factors for survival of the new VA. RESULTS: Three hundred seventeen
      VA have been studied, 73% were arteriovenous fistulas(AVF) and the rest were
      polytetrafluoroethylene (PTFE) grafts at 282 patients. The main causes of
      dysfunctions were elevated dynamic venous pressure (42.5%) and the decreased
      blood flow (36.4%) with a 88% of positive predictive value. Over the 5 years
      there was 88 thrombosis (24 AVF and 64 PTFE grafts), that means a hazard
      thrombosis global rate of 0.15 access/year, which were distributed in 0.06 for
      AVF and 0.38 in PTFE grafts. Two hundred and one repairs of VA were done: 66.6%
      were elective repair after a proper review by the multidisciplinary team and the
      rest of them were done after the AV thrombosis happened. Urgent rescue surgeries
      were done in 76% of the thrombosis. 62.5% of the patients did not need a catheter
      after vascular access thrombosis. The complication relation with AVF and PTFE
      were 11.4% of the total patients hemodialysis hospitalizations. 65.2% of the VA
      were new access. 57% of patients were properly reviewed in the pre-dialysis unit
      at least once and 80% of them start haemodialysis with a mature access. The
      average survival (Kaplan Meier) of the new AVF was 1,575+/-55 days vs 1,087+/-102
      of the PTFE grafts (p < 0.008). The survival after 1, 2 and 3 years for the AVF
      was 89%, 85% and 83% and for the PTFE graft 3% 67% and 51% respectively. The Cox
      regression has proved that the type of vascular access is the strongest factor
      associated to VA survival. The survival added of VA repaired due to dysfunction
      was 1,062 +/- 97 days vs 707 +/- 132 due to thrombosis, log rank 5.17 (p < 0,02).
      The increasing risk of those repaired after a thrombosis vs dysfunction is 4.2 p
      < 0,01. CONCLUSIONS: The monitoring of the vascular access by a multidisciplinary
      team has reached:low rate of thrombosis, high elective number of repairs of the
      VA, high urgent rescue surgery after a thrombosis and a few number catheter
      needed and hospitalizations. AVF are associated with greater survival than PTFE.
      The VA repair due to dysfunction vs thrombosis had a greater survival as well.

PMID- 17227249
TI  - [Vascular access outcome in patients aged over 75 years].
AB  - We report a retrospective study on the results of 132 native fistulas, 12 grafts
      and 27 tunneled catheters followed during 30 months in 144 patients on
      hemodialysis. The results were compared according to patient age: 75 years or
      over (n = 58, 80.3 +/- 3.5) vs below 75 years (n = 86, 59.5 +/- 13.3). Gender,
      presence of diabetes and type of fistula were also included in the analysis.
      RESULTS: There were no statistically significant differences between both groups
      in the use of tunneled catheters or grafts (8.6% vs 5.8% y 5.2% vs 10.5%
      respectively), primary failure of native fistulas (7.1% in those aged 75 years or
      over vs 25.5% in patients below 75 years), rate of thrombosis (0.03 vs
      0.09/patient year at risk respectively) or number of percutaneous or surgical
      procedures in order to maintain the fistula patency (0.11 vs 0.16/patient year at
      risk respectively). At the same time no differences were seen in the primary,
      primary assisted and secondary patency of the native fistulas. The mean age of
      the patients when the first access fistula was created was different according to
      the area of surgery (74.9 +/- 9.3 for the elbow vs 64.9 +/- 16.2 years for the
      forearm, p < 0.005). Diabetes was an unfavourable factor for primary (HR Cox
      2.08, p < 0.05) or secondary (Log Rank, p <0.05) patency. CONCLUSION: The
      vascular access for hemodialysis in elderly patients presents a similar evolution
      to that seen in younger populations if the access creation is based on an
      exhaustive study, including ecodoppler of the vascular map and the use of more
      proximal fistulas if necessary. Therefore the more frequent use of grafts or
      catheters in elderly patients is not justified.

PMID- 17227250
TI  - [Tesio twin catheter system for hemodialysis tunnelized using an echo-guided
      technique. Retrospective analysis of 210 catheters].
AB  - PURPOSE: Review a large experience in the placement of tunnelled catheters to
      assess the outcomes with twin catheter system as hemodialysis access. MATERIAL
      AND METHODS: We retrospectively reviewed clinical and hemodialysis data regarding
      of ESRD patients who were referred from 2 dialysis facilities for placement of
      tunnelled catheters hemodialysis access between 1996 March and 2005 July. For
      catheter insertion a real-time sonography technique was used (Site Rite II Dymax
      corporation) in performing vascular access procedure. The twin catheter system
      available during the study period consisted of 2 x 10-F12. Patients suspected to
      present bacteraemia related to catheter were followed with established protocols.
      Catheter suspected malfunction or thrombosis was treated with low dose Urokinase.
      To evaluated dialysis dose and adequacy, blood flow rates were recorded and Kt/v
      calculated by Daugirdas 2nd generation formula. RESULTS: Overall study period of
      112 months, 210 catheters were inserted in 148 patients(93 males and 55 females,
      mean age 68,6 +/- 4,95 years). 101 catheters were inserted in internal jugular
      vein, 84 in femoral and 25 in subclavian. The successful insertion rate with only
      single needle pass was 87.8%, immediate procedural complications rate was 4.7%.
      The catheters were in place a total of 18,324 days during the study period (mean
      87.2 days; range 4-1,280 days). The mean flow blood rate was 252,4 DS +/- 42.4
      mL/min, Mean Kt/v was 1,21 DS +/- 0,07. Seventy-seven catheters malfunctioned
      during study period, in 55 cases urokinase was effective in recovering blood flow
      rate over 250 mL/min and 25 necessitated removal for ineffective urokinase.
      Infection incidence was 11.9% with bacteraemia related catheter rate of 2.8
      episodes per 1,000 catheter-days, Gram positive bacteria was found in (84%), Gram
      negative in (12%) and others(4%). CONCLUSION: Placement of tunnelled twin
      catheters system using real-time sonography technique can be performed with
      excellent technical success, safety and acceptable catheter performance and
      outcomes for effective hemodialysis.

PMID- 17227251
TI  - [Magnetic resonance hydrography in peritoneal dialysis].

PMID- 17227252
TI  - [Heparin-induced thrombocytopenia in hemodialysis. Case report and review of the
      literature].
AB  - Thrombocytopenia is a potential complication of heparin therapy. There are two
      forms of heparin-induced thrombocytopenia (HIT). Type-I HIT is characterized by a
      mild decrease in platelet count that occurs within the first 2-4 days after
      heparin initiation. The platelet count often returns to normal without stop
      heparin treatment. The mechanism of thrombocytopenia appears to be due to a
      direct effect of heparin on platelet activation. The second form (type-II) is an
      immune-mediated disorder characterized by severe thrombocytopenia, which may
      include both arterial and venous thrombosis. We present a case of type-II HIT
      occurred in a hemodialysis patient resulting in acute pulmonary embolism and
      peripheral venous thrombosis, and review the literature.

PMID- 17227253
TI  - [Prolonged acute renal failure and severe polyradiculopathy in ethylene glycol
      intoxication].
AB  - Ethylene glycol intoxication involves acute renal failure and severe metabolic
      acidosis. Prolonged renal insufficiency can occur but terminal chronic renal
      failure has been reported in very few cases. We describe a patient who after
      ingestion of 920 ml of ethylene glycol developed prolonged acute renal failure
      needing hemodialysis for 37 days and then he partly recovered renal function. The
      patient developed a severe sensitive-motor and autonomic polyradiculopathy.

PMID- 17227254
TI  - [Allopurinol-induced chronic granulomatous interstitial nephritis].
AB  - Although drug induced interstitial nephritis is a relatively common cause of
      renal failure,granulomatous forms remain a rare condition. The development of a
      chronic granulomatous interstitial nephritis due to allopurinol is exceptional,
      only three cases have been described previously. We report on a patient who
      presented a granulomatous interstitial nephritis after 10 years of allopurinol
      administration (300 mg/day). At diagnosis, he had end stage renal disease and
      dialysis treatment was needed. Two months after drug withdrawal and on corticoid
      treatment a slow recovery of renal function was observed, allowing the
      interruption of dialysis. Two years after, the creatinine clearance is 23
      ml/min,being dialysis free. We discuss the differential diagnosis of
      granulomatous interstitial nephritis and its rare association with allopurinol
      treatment.

PMID- 17227255
TI  - [Secondary amyloidosis with irreversible acute renal failure caused by visceral
      leishmaniasis in a patient with AIDS].
AB  - We report a case of visceral leishmaniasis and acute renal failure in a white
      male patient, 28 years of age, infected with the human immunodeficiency virus
      (HIV). The clinical presentation of the patient was diarrheic syndrome of long
      evolution, fever, hepatosplenomegaly and pancytopenia, accompanied by nephrotic
      syndrome and irreversible acute renal failure. Renal biopsy showed glomerular AA
      amyloid deposits. This is the first case described in humans of secondary
      amyloidosis caused by visceral leishmaniasis.

PMID- 17227256
TI  - [Healthcare assistants vis-a-vis living organ donation. An attitudinal study in a
      hospital with a cadaveric and living solid organ transplant program].

PMID- 17227257
TI  - [Acute renal failure associated with severe falciparum malaria].

PMID- 17227258
TI  - [Endocarditis in hemodialysis and prognosis].

PMID- 17227259
TI  - [Cryptosporidiosis. A rare infection in renal transplantation].

PMID- 17227260
TI  - [Anuric acute renal failure due to acetazolamide].

PMID- 17227262
TI  - Enteral nutrition versus glucose-based or lipid-based parenteral nutrition and
      tight glycaemic control in critically ill patients.
AB  - OBJECTIVE: Early administration of nutrition and attention to tight glycaemic
      control are both associated with improved outcomes in critically ill patients. We
      hypothesized that blood glucose control would be better achieved in patients
      receiving enteral rather than parenteral nutrition and, in the latter group,
      would be better achieved using a "balanced" glucose plus lipid solution than a
      dextrose-based solution as calorie source. METHODS: We conducted a retrospective
      interrogation of the intensive care database as part of a clinical audit of a 12
      bed mixed medical and surgical ICU in a tertiary referral teaching hospital
      between September 2003 and March 2004. Patients expected to stay in the ICU for
      longer than 48 hours were treated according to an intensive insulin therapy
      protocol. They received enteral nutrition (EN) or, if EN was not tolerated,
      parenteral nutrition (PN) or combined EN and PN. PN comprised a glucose-based
      solution (GluPN) during the first 3 months of the study and a balanced glucose
      plus lipid solution (LipPN) during the second 3 months. RESULTS: 96 patients were
      treated according to the protocol. Patients receiving PN (n = 26) had
      significantly longer ICU length of stay and greater daily caloric intake than did
      those receiving EN (n = 70) during both study periods. Mean blood glucose,
      percentage of blood glucose measurements within the target range, and daily
      insulin dose did not differ significantly between patients receiving EN and PN or
      GluPN and LipPN. CONCLUSION: When used in association with a tight glycaemic
      control regimen, PN is not associated with poorer glycaemic control in critically
      ill patients than EN.

PMID- 17227263
TI  - A phase II randomised controlled trial of intensive insulin therapy in general
      intensive care patients.
AB  - OBJECTIVE: To determine the safety and efficacy of an intensive insulin regimen
      compared with a conventional insulin regimen in general intensive care unit
      patients. METHODS: A phase II, randomised controlled trial was conducted in 70
      critically ill patients in a closed multidisciplinary ICU of a university
      affiliated tertiary hospital. We assessed patient characteristics at baseline.
      Trial process measures included number of blood glucose measurements per day and
      number in target range, type and quantity of caloric intake, patient outcome and
      insulin dosing. The primary outcome was the median blood glucose concentration.
      Secondary outcome measures were incidence of hypoglycaemia (blood glucose level <
      2.2 mmol/L), clinical sequelae of hypoglycaemia and hospital mortality. RESULTS:
      Thirty-five patients were randomised to each of the two groups. More blood
      glucose samples were taken per day in the intensive insulin group (16 versus 9),
      but the number of samples in the normoglycaemic range was 48.5%, compared with
      79.8% within the target glucose range in the conventional insulin group. The
      median (interquartile range) blood glucose concentrations in the intensive and
      conventional insulin therapy groups were 5.4 (5.1-5.7) mmol/L and 7.9 (7.2-9.0)
      mmol/L, respectively (difference, 2.5 mmol/L; P < 0.0001). Five patients (14.3%)
      in the intensive insulin therapy group became hypoglycaemic versus none in the
      conventional insulin therapy group. There were no detected clinical sequelae of
      hypoglycaemia. CONCLUSION: The intensive insulin regimen was effective in
      achieving the target blood glucose concentration, with clear separation from the
      conventional insulin regimen. Although the incidence of hypoglycaemia was
      increased, there was no detectable harm.

PMID- 17227264
TI  - Effect of heparin in arterial line flushing solutions on platelet count: a
      randomised double-blind study.
AB  - INTRODUCTION: Arterial catheters are widely used in intensive care units for
      continuous blood pressure monitoring and blood sampling. Studies have examined
      the effect of heparin on patency of arterial catheters but not on platelet
      counts. Heparin is a naturally occurring anticoagulant that helps prevent
      clotting and is given to prevent and treat thrombosis. It has many other effects,
      including reducing platelet counts. METHODS: A prospective, randomised, double
      blind study compared the effects of heparinised and normal saline (both
      administered via a continuous flush device to an arterial catheter) on patients'
      platelet counts. All patients admitted to a mixed medical-surgical ICU between
      April and December 2003 were eligible for entry. Exclusion criteria were age
      under 16 years, known sensitivity to heparin, pre-existing coagulopathy that
      precluded heparin, or requirement for therapeutic heparin. Lines were inserted
      into radial, brachial or femoral arteries. A 500 mL bag of saline for the flush
      was injected with numbered syringes, containing either normal saline (NS, 35
      patients) or 500 IU heparin (HS, 30 patients), and pressurised. Platelet count
      was assessed daily. RESULTS: Mean platelet counts were 234.6 x 10(9)/L (NS)
      versus 256.6 x 10(9)/L (HS). Comparison using the central limit theorem showed
      means were not different at the 95% confidence interval (- 77.6 to 37 x 10(9)/L).
      CONCLUSION: Use of heparin in normal saline as a continuous flush for an arterial
      catheter does not reduce platelet counts in critically ill patients.

PMID- 17227265
TI  - Continuous negative extrathoracic pressure in children after congenital heart
      surgery.
AB  - OBJECTIVE: To study the effects of continuous negative extrathoracic pressure
      (CNEP) in children after surgery for congenital heart defects. METHODS: We
      applied - 3 to - 6 cmH2O CNEP with a cuirass and ventilator to 16 infants and
      children managed in a paediatric intensive care unit after surgery for congenital
      heart defects between July 2003 and July 2004. Changes in haemodynamics and gas
      exchange were assessed 1h and 8h after CNEP application. All patients were
      breathing spontaneously after successful extubation while receiving CNEP.
      RESULTS: Patients were aged 1-34 months (median, 11.5 months). Six had undergone
      right heart bypass surgery (Group A), and 10 had received positive pressure
      ventilation for >48 h after other types of heart surgery (Group B). Urine output
      increased significantly, by 49% at 1 h in Group A, and by 65% in Group B.
      Decreases in central venous pressure, from median (range) of 15 (12-22)mmHg to 12
      (10-21) mmHg in Group A, and from 9 (5-13)mmHg to 8.5 (5-12)mmHg in Group B, and
      tendency to increases in arterial blood pressure were observed after 1h. In Group
      B, oxygen saturation increased from 96.5% (84%-100%) at baseline to 99% (87%
      100%) and 100% (88%-100%) at 1 h and 8 h, respectively. CONCLUSION: Prophylactic
      application of CNEP immediately after extubation appears to decrease right
      ventricular load and improve arterial oxygenation. CNEP might become a useful
      option in the management of congenital heart surgery patients.

PMID- 17227266
TI  - Long-term outcome of acute respiratory distress syndrome caused by severe acute
      respiratory syndrome (SARS): an observational study.
AB  - OBJECTIVE: We examined long-term outcome of pulmonary function, exercise capacity
      and health-related quality of life (HRQoL) in patients with acute respiratory
      distress syndrome (ARDS) caused by severe acute respiratory syndrome (SARS).
      METHODS: 59 critically ill patients with ARDS caused by SARS between March and
      July 2003 were studied prospectively and followed up for 1 year. Thirty-six
      underwent pulmonary function testing and a 6-minute walk test, and 35 underwent
      HRQoL evaluation by Short Form-36 questionnaire at 3, 6, and 12 months after
      illness onset. RESULTS: Mean age was 47 (SD, 15.7) years. Median APACHE II score
      was 10 (interquartile range [IQR], 7-12). Only 47% required invasive mechanical
      ventilation. Median admission and worst PaO2/FIO2 ratio were 142 (IQR, 94-177)
      mmHg and 86 (IQR, 66-122) mmHg, respectively. Median stay in ICU and hospital
      were 9 (IQR, 5-20) and 31 (IQR, 20-54) days, respectively. Mortality was 24% at
      hospital discharge and at 1 year. Mean lung volumes and spirometric measurements
      were nearly normal by 6 months. Except for diffusion capacity adjusted for
      haemoglobin concentration (DLCO) measured at 12 months, there was no significant
      difference in pulmonary function measurement between those who had mechanical
      ventilation and those who did not. The 6-minute walk distance (6MWD) improved
      from 3 to 6 months, with no further significant change. Younger patients had near
      normal HRQoL by 6 months. Those aged over 40 years had impaired HRQoL at multiple
      domains even at 12 months. At 12 months, forced expiratory volume in 1 second,
      forced vital capacity and 6MWD correlated significantly with multiple SF-36
      domain scores. DLCO correlated significantly only with domain scores reflecting
      physical function. CONCLUSIONS: The mortality of SARS-related ARDS is similar to
      the mortality of ARDS from other causes. A substantial number of patients with
      SARS-related ARDS survived without receiving mechanical ventilation. Patients had
      good recovery of pulmonary function and HRQoL.

PMID- 17227267
TI  - Measurement of cardiac output with a non-invasive continuous wave Doppler device
      versus the pulmonary artery catheter: a comparative study.
AB  - INTRODUCTION AND AIM: Cardiac index remains an important measured variable used
      to optimise fluid and haemodynamic support in the postoperative cardiac setting.
      Recent developments in non-invasive continuous wave Doppler devices enable rapid
      assessment of cardiac index with decreased morbidity. This study aimed to
      determine the clinical utility of one such device, the USCOM device (USCOM Ltd,
      Sydney, NSW), in assessing cardiac index compared with invasive continuous
      measurements of cardiac index using a pulmonary artery (PA) catheter. METHODS: A
      prospective study was undertaken in patients admitted to an intensive care unit
      after cardiac revascularisation, open-heart surgery or cardiac or pulmonary
      transplant, most of whom required haemodynamic support. Cardiac index was
      measured by a single operator using the USCOM device. Continuous cardiac index
      measurements using the PA catheter were obtained (blinded to USCOM measurements)
      within 15 minutes of the USCOM measurement. RESULTS: 30 patients were enrolled.
      Adequate Doppler signals were obtained in 26, yielding 34 paired measurements.
      Comparison of the two methods using a Bland-Altman analysis identified a bias of
      0.22 with limits of agreement of - 1.17 (- 1.53 to - 0.82) and 1.62 (1.26 to
      1.97), representing limits of agreement for interchangeability of 52%.
      CONCLUSION: In a heterogeneous population of postoperative cardiac patients, non
      invasive determination of cardiac index using USCOM had limited clinical utility.
      Doppler flow signal quality may have been affected by intrathoracic air, patient
      position and operator learning curve. Given accepted inherent inaccuracies of
      continuous cardiac output assessment, further investigation is required to
      validate the suitability of USCOM in this patient population.

PMID- 17227268
TI  - End-of-life care in the intensive care unit: the Irish Ethicus data.
AB  - OBJECTIVE: To study the frequency, rationale and process for withholding (WH) and
      withdrawing (WD) life-sustaining therapies in intensive care patients in Ireland.
      DESIGN: Prospective, observational study, comprising a subset of the European
      Ethicus Study. SETTING AND PARTICIPANTS: 122 patients who died or who had life
      sustaining therapies limited in the ICU of a university hospital, 1 September
      1999 to 30 June 2000. OUTCOME MEASURES AND RESULTS: An end-of-life (EOL)
      treatment decision was made for 85/122 patients (69%). Forty-five (36%) had
      therapy withheld, 40 (33%) had it withdrawn, 26 (21%) had unsuccessful
      cardiopulmonary resuscitation, and 11 (10%) suffered brain death. The median time
      from ICU admission to death was 4.0 days for WH patients and 2.9 days for WD
      patients (range, 10 minutes to 123 days). The discussion to limit therapy was
      initiated by the ICU doctor in 50 cases (59%), and involved families in 66 cases
      (78%). Families initiated 9% of EOL discussions. Nursing staff were involved in
      98% of decisions. No patients were mentally competent, but their wishes were
      known in 28% of cases. The primary reason for limiting life-sustaining therapy
      was that the patient was unresponsive to maximum therapy (68% of patients). An
      EOL decision was made every 55 hours during "office hours" and every 120 hours
      during "on-call" working hours. Withholding was more frequent than withdrawing
      during "on call" periods. DISCUSSION: The frequency of withdrawal or withholding
      of therapy in this Irish ICU is in line with current international practice. The
      time to EOL decision-making is variable and relatively short compared with that
      in the United States, but similar to that in Europe. Clinicians are the primary
      initiators of the EOL decision in Ireland, with little patient involvement.
      Family members are more likely to initiate an EOL decision than in Europe. EOL
      decisions were usually made during "routine" working hours after significant
      consultation with all groups.

PMID- 17227269
TI  - Survival after out-of-hospital cardiac arrest in Sydney, Australia.
AB  - BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a significant cause of
      death, but there is little published information on its incidence and outcomes in
      Australia. AIM: This study was undertaken to determine the incidence and survival
      from OHCA in Sydney, New South Wales. METHODS: Patients listed on the Ambulance
      Service of NSW database as having an OHCA during the 12-month period 1 June 2004
      to 31 May 2005 were matched with the NSW Registry of Births, Deaths and Marriages
      to determine if they had died, and how long they survived. Survival was also
      determined for patients aged 80 years or older, and for the presenting
      electrocardiograph (ECG) rhythm. RESULTS: OHCAs were recorded for 2011 people in
      a population of 3.993 million. The age-standardised incidence was 52.6 events per
      100,000 person-years (95% CI, 51.6-53.6). Incidence was significantly higher in
      older age groups. Only 24% of patients survived past the day of the OHCA.
      Survival for 28 days, 90 days and 1 year was 12.6%, 12.2%, and 11.5%,
      respectively. Survival was highest when the presentation ECG was ventricular
      fibrillation. Patients aged 80 years or older had lower survival rates.
      CONCLUSION: Survival from OHCA in Sydney is low, and lower in patients aged 80
      years or older. The incidence of OHCA in Sydney is similar to that in the rest of
      the world. Mortality occurs early after OHCA. Hence, for interventions to be
      effective in improving survival, they need to be targeted at the early stages of
      OHCA.

PMID- 17227270
TI  - The effect of extubation failure on outcome in a multidisciplinary Australian
      intensive care unit.
AB  - BACKGROUND: A reported association between extubation failure (EF) and increased
      hospital length of stay and mortality led us to assess outcome of EF in an
      Australian intensive care unit. DESIGN AND SETTING: Non-interventional cohort
      study in the intensive care/high dependency unit of a tertiary referral hospital,
      2000-2003. METHODS: EF was defined as reintubation within 72 hours of extubation.
      Causes of EF were determined by review of the clinical notes and prospective
      record of the EF event. Patients were excluded if they were aged < or = 14 years,
      self-extubated, were reintubated to replace a defective endotracheal tube, or had
      been extubated but were returning to the operating theatre. Physiological
      variables used to calculate severity of illness score were analysed to ascertain
      correlation with EF. RESULTS: 2761 patients were electively extubated, and 52
      (1.8%) fulfilled the criteria for EF. Compared with those successfully extubated,
      EF patients had a higher 24 h APACHE II score (18.0+/-7.0 [mean+/-SD] v 15.3+/
      7.4, P=0.009), significant increases in length of stay in ICU (12.8+/-8.3 v 3.0+/
      6.0 days, P<0.001) and hospital (33.5 +/-40.8 v 18.0+/-28.6 days, P<0.001) and
      tracheostomy rate (38.5% v 3.5%, P<0.001). The commonest cause of EF was excess
      secretions or aspiration (32%). EF was independently associated with hospital
      mortality (odds ratio [OR], 2.10; 95% CI, 1.00-4.41; P=0.048) and low serum
      albumin level on admission (OR, 0.75; 95% CI, 0.55-1.00; P=0.05). Neither
      aetiology of airway failure (OR, 2.21; 95% CI, 0.56- 8.75; P=0.25) nor time to
      reintubation (OR, 0.99; 95% CI, 0.97-1.01; P=0.76) were associated with
      mortality. CONCLUSION: Our findings confirm an increased risk of adverse outcomes
      for patients with EF. We observed a comparatively low EF rate. Confirmation in
      similar patient cohorts is required.

PMID- 17227271
TI  - Impact of manufacturing improvements on clinical safety of albumin: Australian
      pharmacovigilance data for 1988-2005.
AB  - OBJECTIVE: To evaluate the impact of manufacturing improvements on the clinical
      safety of human albumin solutions in Australia. METHODS: This retrospective study
      examined the incidence of spontaneously reported post-market adverse drug
      reactions (ADRs) in Australia associated with successive generations of albumin
      products manufactured by the Bioplasma Division of CSL Limited (CSL Bioplasma)
      over 18 years (1988-2005). Key characteristics of each product generation which
      could affect clinical safety, such as purity, aggregates and prekallikrein
      activator (PKA) levels, were also identified from CSL batch release records.
      RESULTS: A total of 3.7 million bottles of iso-oncotic and hyperoncotic albumin
      products were distributed in Australia over the period. Improvements to
      manufacturing processes resulted in products with increased albumin purity, lower
      levels of impurities such as aggregates and PKA, and reduced batch-to-batch
      variation. The total ADR incidence (number of ADRs per 100 000 bottles
      distributed) associated with the products currently supplied was 1.5 and 1.7 for
      Albumex 4 (2VI) and Albumex 20 (2VI), respectively. This was a significant
      reduction compared with the earlier generation products Stable Plasma Protein
      Solution (14.1) and 20% Normal Serum Albumin (11.5), respectively (P<0.0001). In
      particular, hypotensive reactions declined substantially. CONCLUSION: Post-market
      pharmacovigilance data collected for successive generations of human albumin
      products supplied in Australia over 18 years indicates that manufacturing
      improvements have significantly improved the clinical safety profile of this
      product.

PMID- 17227272
TI  - Conservative management of flail chest after cardiopulmonary resuscitation by
      continuous negative extrathoracic pressure.
AB  - Flail chest after blunt trauma usually requires good pain control and positive
      pressure support. Continuous negative extrathoracic pressure (CNEP) causes a
      splinting effect around the anterior chest wall and upper abdomen which increases
      functional residual capacity and improves lung mechanics. We report an 82-year
      old woman with flail chest after cardiopulmonary resuscitation. She underwent
      mechanical ventilation, with two failed attempts at extubation. She was
      subsequently ventilated non-invasively using CNEP, allowing early successful
      extubation. This case illustrates the use of CNEP for weaning and ventilating
      patients with flail chest after blunt trauma.

PMID- 17227273
TI  - An unusual case of vascular catastrophe.
AB  - Thrombotic thrombocytopenic purpura (TTP) has been recognised as an entity since
      1924, and haemolytic uraemic syndrome (HUS) since 1955. The disease processes
      have generated new interest during the past two decades, and much progress has
      been made both in understanding and treating these diseases. They are best
      thought of as part of the same disease spectrum, characterised by
      thrombocytopenia and microangiopathic haemolytic anaemia on the blood film. We
      present a patient with HUS/ TTP who developed the macroangiopathic thrombotic
      complications of coronary occlusion causing myocardial infarction, and cerebral
      artery occlusion causing massive stroke. To our knowledge, this is the first
      published report of macroangiopathic complications of this condition.

PMID- 17227274
TI  - Heparin-induced thrombocytopenia without thrombosis: an evidence-based review of
      current literature.
AB  - BACKGROUND AND AIM: There has been a recent change in the management guidelines
      for patients with heparin-induced thrombocytopenia with the addition of a
      recommendation to commence parenteral anticoagulation in patients with isolated
      HIT without evidence of thrombosis. We assessed the evidence supporting this
      recommendation, to answer the following questions: in a patient with isolated
      HIT, should alternative anticoagulation be commenced, what alternative agent
      should be used, what is the recommended duration of anticoagulation, and when
      should warfarin be used? METHODS: We searched MEDLINE (using keywords "heparin
      induced thrombocytopenia", "heparin induced thrombocytopaenia", "HIT" and
      "HITTS") and PubMed (using MeSH terms "thrombocytopenia" and "heparin") from 1966
      to 2006 and selected articles for further assessment according to specified
      criteria. RESULTS: We assessed 12 non-randomised studies, five large case series
      and multiple small case series. CONCLUSION: Although patients with isolated HIT
      are at considerable risk of new thrombosis, there is limited evidence to support
      or reject the use of non-heparin anticoagulation in this group. Non-randomised,
      historically controlled trials support the use of lepirudin and argatroban;
      evidence favouring danaparoid is limited to large case series and one
      retrospective observational study. Duration of parenteral anticoagulation and
      warfarin use are guided by consensus opinion alone.

PMID- 17227275
TI  - An appraisal of selection and use of catecholamines in septic shock - old becomes
      new again.
AB  - The use of catecholamines to defend and resuscitate patients with septic shock
      remains a cornerstone of intensive care medicine. The pharmacological support of
      the failing circulation during sepsis and septic shock should be directed at
      augmenting perfusion of vital organs and facilitating venous return, rather than
      peripheral arterial vasoconstriction. There appears to be a teleological
      rationale for primary use of catecholamines to augment failing endogenous
      neurohumoral and neuroendocrine cardiovascular systems. To this end, it seems
      intuitive to use the predominant naturally occurring catecholamine,
      noradrenaline, as the first-line agent for circulatory failure, although there
      are no definitive clinical trials to support this. Adrenaline has an established
      place in many parts of the world, particularly low-income countries, and appears
      to be equivalent to noradrenaline for reversing septic shock. There is increasing
      evidence for adverse neuroendocrine and immunological effects of dopamine,
      warranting circumspection about its use. The use of synthetic inotropes and
      vasopressors for septic shock remains limited, with little biological rationale.
      Clinicians should wait for definitive outcome-based trials of these expensive
      agents before incorporating them into practice. Supplemental endocrine
      replacement therapy with low-dose corticosteroids and vasopressin appears
      biologically plausible and has an emerging role. Results of large-scale, high
      quality trials of endogenous catecholamines for sepsis and septic shock are
      awaited. These may provide additional, important information for evidence-based
      guidelines, which currently remain of limited clinical utility.

PMID- 17227277
TI  - Chronic hyponatraemia and risk of myelinolysis: why is it so difficult to control
      the change in plasma sodium?

PMID- 17227276
TI  - Australasian trends in intra-aortic balloon counterpulsation weaning: results of
      a postal survey.
AB  - OBJECTIVE: To generate baseline data describing Australasian intra-aortic balloon
      counterpulsation (IABP) weaning practice. METHODS: A five-part questionnaire was
      mailed in April 2005 to all 192 intensive care units in Australia and New
      Zealand. RESULTS: 116 ICUs responded (response rate, 60%), and 54 reported using
      IABP. Most of the 54 were in hospitals which were public government-funded (65%),
      had between 100 and 500 beds (69%), and treated a minimum of 11 patients annually
      with IABP (60%). The most common method of withdrawing IABP support was ratio
      reduction alone (61%). ICUs most likely to undertake ratio weaning were higherend
      users of IABP (> 20 cases per annum) (P = 0.04). Other weaning practices involved
      a combination of ratio followed by volume reduction (17%), volume then ratio
      (11%), and volume only (4%). Approaching statistical significance, ratio
      reduction weaning less frequently required IABP reinsertion or inotropic increase
      after balloon removal (P = 0.07). ICUs with documented weaning policies were less
      likely to require IABP reinsertion or inotropic increase after balloon removal (P
      = 0.06). Criteria considered important before IABP weaning or removal were: blood
      pressure (92%); heart rate (76%); pulmonary artery wedge pressure (59%);
      noradrenaline dose (78%); adrenaline dose (57%); and dobutamine dose (57%).
      Ninety per cent of ICUs reported increasing inotropes after balloon removal only
      rarely (1:50 patients) or occasionally (1:10 patients), while 87% of ICUs
      reported never needing to reinsert the balloon or only rarely. CONCLUSION: The
      Australasian approach to IABP weaning is eclectic. While ratio reduction weaning
      appears the most successful manner of support withdrawal, it may be a consequence
      of a volume-outcome relationship, with high- end users achieving better results
      through IABP familiarity.

PMID- 17227278
TI  - Relative adrenocorticoid insufficiency exists and should be treated.
AB  - The issue of relative adrenocortical insufficiency (RAI) in septic shock is
      confused and uncertain. Multiple definitions of RAI have been proposed, but it is
      most commonly defined as an increment of less than 250 nmol/L in total serum
      cortisol level after administration of 250 microg corticotropin. RAI is
      associated with an increased risk of death, after adjustment for other factors
      that might independently influence risk. It is likely that the definition of RAI,
      if it exists, will be modified in the future, based on research that measures the
      level of free serum cortisol (the active fraction), rather than total serum
      cortisol (as currently measured). There is strong, but not overwhelming, evidence
      that administration of low doses of hydrocortisone to patients with septic shock,
      especially those with RAI, improves survival.

PMID- 17227279
TI  - Relative adrenal insufficiency in sepsis: match point or deuce?

PMID- 17227280
TI  - Reflections on being the first Japanese fellow of the joint faculty of intensive
      care medicine.

PMID- 17227281
TI  - Notable Australian contributions to the management of ventilatory failure of
      acute poliomyelitis: with special reference to the Both respirator and Dr. John
      A. Forbes.
AB  - When Australia's 1937 epidemic of poliomyelitis created an urgent need for extra
      ventilating machines to compensate for respiratory paralysis, Edward Both, an
      innovative Adelaide biomedical engineer, invented a wooden-cabinet respirator
      capable of being made relatively quickly in sufficient quantity. His device, here
      called "the Both", alleviated the problem at Adelaide's Northfield Infectious
      Diseases Hospital and others, and in late 1938 was introduced into England when
      Both was visiting there. Appreciating its merits, Lord Nuffield financed assembly
      line production at the Morris motor works in Cowley, Oxford. Then, through the
      Nuffield Department of Anaesthetics in Oxford's Radcliffe Infirmary, he had the
      Both distributed Commonwealth-wide, as a gift for treating ventilatory failure in
      polio - especially in children. For the 1937 epidemic in Victoria, and to the
      design of Melbourne University's Professor of Engineering, Aubrey Burstall,
      nearly 200 of another wooden-cabinet respirator were ultimately built. Some were
      installed at the Acute Respiratory Unit of the Infectious Diseases Hospital at
      Fairfield, then others "all over Australia". However, by the early 1950s, the
      Both had replaced Fairfield Hospital's "Burstall", which had functioned as
      Victoria's favoured respirator since 1937. Dr John Forbes at Fairfield became the
      foremost Australian clinician for expertise with the Both. Before the advent of
      intermittent positive pressure ventilation, the Both's usefulness had seen it
      tried for ventilatory failure in some non-polio conditions, but uptake of that
      application was limited. Nonetheless, Nuffield's philanthropy with the (Nuffield
      )Both ultimately furthered progress along the 20th century pathway to intensive
      care medicine.

PMID- 17227282
TI  - Radiologically assisted cerebrospinal fluid sampling in a morbidly obese patient.

PMID- 17227283
TI  - "In the Flesh: the Monro Dynasty 1720-1846" is now online.

PMID- 17227284
TI  - Biomaterials and scaffold design: key to tissue-engineering cartilage.
AB  - Cartilage remains one of the most challenging tissues to reconstruct or replace,
      owing to its complex geometry in facial structures and mechanical strength at
      articular surfaces in joints. This non-vascular tissue has poor replicative
      capacity and damage results in its functionally inferior repair tissue,
      fibrocartilage. This has led to a drive for advancements in tissue engineering.
      The variety of polymers and fabrication techniques available continues to expand.
      Pore size, porosity, biocompatibility, shape specificity, integration with native
      tissue, degradation tailored to rate of neocartilage formation and cost
      efficiency are important factors which need consideration in the development of a
      scaffold. The present review considers the current polymers and fabrication
      methodologies used in scaffold engineering for cartilage and postulates whether
      we are closer to developing the ideal scaffold for clinical application.

PMID- 17227285
TI  - Pharmacological profile of the 5-HT(2C) receptor agonist WAY-163909; therapeutic
      potential in multiple indications.
AB  - The 5-HT(2C) receptor subtype has been implicated in a wide variety of conditions
      including obesity, anxiety, depression, obsessive compulsive disorder,
      schizophrenia, migraine and erectile dysfunction and as a consequence has
      received considerable attention as a target for drug discovery. Here we review
      the pharmacological, pharmacokinetic and toxicological profile of WAY-163909
      {(7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta
      [b][1,4]diazepino[6,7,1hi]indole}, a novel 5-HT(2C) receptor selective agonist.
      Consistent with a potential therapeutic utility in obesity, schizophrenia and
      depression WAY-163909 was found to have robust dose-dependent effects in animal
      models of obesity, psychotic-like behavior or depression.

PMID- 17227286
TI  - Review of the pharmacology and clinical profile of bupropion, an antidepressant
      and tobacco use cessation agent.
AB  - Bupropion hydrochloride ((+/-)-2-tert-butylamino)-3'-chloropropiophenone x HCl)
      is a nonselective inhibitor of the dopamine transporter (DAT) and the
      norepinephrine transporter (NET) and is also an antagonist at neuronal nicotinic
      acetylcholine receptors (nAChRs). In animal models used commonly to screen for
      antidepressant activity, bupropion shows a positive response. Also using animal
      models, bupropion has been shown to attenuate nicotine-induced unconditioned
      behaviors, to share or enhance discriminative stimulus properties of nicotine and
      to have a complex effect on nicotine self-administration, i.e., low doses
      augmenting nicotine self-administration and high doses attenuating self
      administration. Current studies show that bupropion facilitates the acquisition
      of nicotine conditioned place preference in rats, further suggesting that
      bupropion enhances the rewarding properties of nicotine. Bupropion has been shown
      to attenuate the expression of nicotine withdrawal symptoms in both animal models
      and human subjects. With respect to relapse, current studies show that bupropion
      attenuates nicotine-induced reinstatement in rats, but large individual
      differences are apparent. Clinically, bupropion is used as a treatment for two
      indications, as an antidepressant, the indication for which it was developed, and
      as a tobacco use cessation agent. In clinical trials, bupropion is being tested
      as a candidate treatment for psychostimulant drug abuse, attention-deficit
      hyperactivity disorder (ADHD) and obesity. Bupropion is available in three
      bioequivalent oral formulations, immediate release (IR), sustained release (SR),
      and extended release (XL). Extensive hepatic metabolism of bupropion produces
      three pharmacologically active metabolites, which may contribute to its clinical
      profile.

PMID- 17227288
TI  - Silperisone: a centrally acting muscle relaxant.
AB  - Silperisone is a tolperisone like organosilicon compound with centrally acting
      muscle relaxant properties. Studies in mice showed that silperisone may have less
      propensity to cause CNS depressant or motor side effects than tolperisone or
      other antispastic drugs. In cats and rats, silperisone was an effective
      suppressant of monosynaptic and polysynaptic spinal reflexes and decerebrate
      rigidity. Its suppressant effect on the spinal reflexes was also demonstrated in
      the isolated hemisected rat spinal cord in vitro. The in vivo potency and
      efficacy of silperisone by i.v administration were similar to those of
      tolperisone and eperisone. However, in cats by intraduodenal administration and
      in mice by oral administration its duration of action was much longer and its
      functional bioavailability much higher than of the other two drugs. With regard
      to its profile of actions silperisone was similar to tolperisone with minor
      differences. The most striking difference was in pontine facilitation and bulbar
      inhibition of the patellar reflex. Tolperisone depressed both, whereas
      silperisone inhibited only the former. The mechanism underlying the spinal reflex
      depressant effects of silperisone involves the blockade of voltage gated neuronal
      sodium and calcium channels leading to a decreased release of excitatory
      transmitter and reduced neuronal excitability. In addition, silperisone has
      potassium channel blocking effect, which is stronger than that of tolperisone.
      Silperisone is absorbed rapidly and is extensively metabolized in rats. However,
      its metabolism in dogs and particularly in humans is much less extensive. The
      elimination half-life of silperisone in humans is 12 to 16 h, so that it can be
      administered once or twice daily. Phase I clinical studies with silperisone at
      doses up to 150 mg/day failed to detect any adverse effects at plasma
      concentrations considered to be effective in the preclinical tests. These
      findings suggested that silperisone might be a useful antispastic drug. However,
      findings in chronic animal toxicity studies led to the discontinuation of
      silperisone's development.

PMID- 17227289
TI  - A new look at the respiratory stimulant doxapram.
AB  - A number of life-threatening clinical disorders may be amenable to treatment with
      a drug that can stimulate respiratory drive. These include acute respiratory
      failure secondary to chronic obstructive pulmonary disease, post-anesthetic
      respiratory depression, and apnea of prematurity. Doxapram has been available for
      over forty years for the treatment of these conditions and it has a low side
      effect profile compared to other available agents. Generally though, the use of
      doxapram has been limited to these clinical niches involving patients in the
      intensive care, post-anesthesia care and neonatal intensive care units. Recent
      basic science studies have made considerable progress in understanding the
      molecular mechanism of doxapram's respiratory stimulant action. Although it is
      unlikely that doxapram will undergo a clinical renaissance based on this new
      understanding, it represents a significant advance in our knowledge of the
      control of breathing.

PMID- 17227287
TI  - Augmentation treatment of psychotherapy for anxiety disorders with D-cycloserine.
AB  - Anxiety disorders are among the most common mental disorders. One of the most
      effective strategies to treat anxiety disorders is exposure therapy with or
      without cognitive intervention. Fear reduction in exposure therapy is similar to
      extinction learning. Preclinical studies suggest that extinction learning can be
      blocked by antagonists at the glutamatergic N-methyl-D-aspartate (NMDA) receptor,
      and facilitated with D-cycloserine (DCS), a partial agonist at the glycine
      recognition site of the NMDA receptor in the amygdala. DCS is an established
      antibiotic drug for the chronic treatment of tuberculosis in humans, but has only
      recently been investigated as an augmentation therapy for psychological treatment
      procedures. The review of the literature provides preliminary support for the use
      of acute dosing of DCS as an adjunctive intervention to exposure therapy for
      anxiety disorders, including specific phobia and social anxiety disorder.
      Negative results have recently been reported in the treatment of subclinical
      fears of animals. These studies suggest that DCS needs to be administered on an
      acute rather than a chronic dosing schedule, include sufficient time for memory
      consolidation, and be administered together with psychological treatment that
      leaves sufficient room for further improvement. It remains to be seen whether
      these highly promising findings represent reliable pharmacological strategies to
      enhance exposure therapy of anxiety disorders.

PMID- 17227290
TI  - Paracetamol: new vistas of an old drug.
AB  - Paracetamol (acetaminophen) is one of the most popular and widely used drugs for
      the treatment of pain and fever. It occupies a unique position among analgesic
      drugs. Unlike NSAIDs it is almost unanimously considered to have no
      antiinflammatory activity and does not produce gastrointestinal damage or
      untoward cardiorenal effects. Unlike opiates it is almost ineffective in intense
      pain and has no depressant effect on respiration. Although paracetamol has been
      used clinically for more than a century, its mode of action has been a mystery
      until about one year ago, when two independent groups (Zygmunt and colleagues and
      Bertolini and colleagues) produced experimental data unequivocally demonstrating
      that the analgesic effect of paracetamol is due to the indirect activation of
      cannabinoid CB(1) receptors. In brain and spinal cord, paracetamol, following
      deacetylation to its primary amine (p-aminophenol), is conjugated with
      arachidonic acid to form N-arachidonoylphenolamine, a compound already known
      (AM404) as an endogenous cannabinoid. The involved enzyme is fatty acid amide
      hydrolase. N-arachidonoylphenolamine is an agonist at TRPV1 receptors and an
      inhibitor of cellular anandamide uptake, which leads to increased levels of
      endogenous cannabinoids; moreover, it inhibits cyclooxygenases in the brain,
      albeit at concentrations that are probably not attainable with analgesic doses of
      paracetamol. CB(1) receptor antagonist, at a dose level that completely prevents
      the analgesic activity of a selective CB(1) receptor agonist, completely prevents
      the analgesic activity of paracetamol. Thus, paracetamol acts as a pro-drug, the
      active one being a cannabinoid. These findings finally explain the mechanism of
      action of paracetamol and the peculiarity of its effects, including the
      behavioral ones. Curiously, just when the first CB(1) agonists are being
      introduced for pain treatment, it comes out that an indirect cannabino-mimetic
      had been extensively used (and sometimes overused) for more than a century.

PMID- 17227292
TI  - Progression of astrocytomas and meningiomas: an evaluation in vitro.
AB  - OBJECTIVES/BACKGROUND: In biological terms, progression means that malignancy
      increases as genetic mutations accumulate leading to increased proliferation and
      invasion capacity. By verifying the proliferation capacity, human telomerase
      reverse transcriptase (hTERT) expression and in vitro invasion, in a group of
      highly malignant glioblastomas, benign meningiomas and astrocytomas, at the
      initial stage of progression, we have analysed putative progression in vitro for
      proliferation and telomerase expression. MATERIALS AND METHODS: The relative
      proliferation status (visualized with Ki-67 antibodies) and presence of hTERT
      protein was analysed in 27 intracranial tumours (6 astrocytomas, 8 glioblastomas
      and 13 meningiomas) by immunohistochemistry on paraffin-embedded biopsy tissue,
      as well as on primary tumour-derived cell cultures. A confrontation model was
      used to analyse invasiveness in vitro. RESULTS: The mean proliferation indices
      were 22.3 (SD = 18.1) for glioblastomas and 2.1 (SD = 1.9) for low-grade (LG)
      astrocytomas. The group of benign meningiomas had a labelling index of 2.2 (SD =
      2.7). Mean percentages of staining for hTERT varied between 36.5 (SD = 28.4) for
      glioblastomas and 10.2 (SD = 8.6) for LG astrocytomas. The group of benign
      meningiomas had a labelling index of 12.4 (SD = 19.2) for hTERT. A significant
      difference was seen for Ki-67 (P < 0.05) and hTERT (P < 0.001) in vivo versus in
      vitro. No difference was seen between the group of invasive and non-invasive
      tumour-derived cell cultures for the histopathological markers Ki-67 and hTERT (P
      > 0.05) in vitro. CONCLUSIONS: The elevated expression of hTERT and Ki-67 in
      vitro provides a potential prognostic tool for early detection of the progression
      of brain tumours. As tumour cells require telomerase for continued proliferation,
      the expression of hTERT may mark immortality, leading to indefinite life span. On
      the other hand, hTERT expression and cell proliferation are not linked directly
      to invasion in vitro.

PMID- 17227291
TI  - Constitutive histone H2AX phosphorylation and ATM activation are strongly
      amplified during mitogenic stimulation of lymphocytes.
AB  - OBJECTIVES: We recently postulated that constitutive activation of Ataxia
      Telangiectasia, Mutated (CAA) and constitutive histone H2AX phosphorylation (CHP)
      seen in cells not treated with genotoxic agents are the events triggered by DNA
      damage caused by endogenous reactive oxygen species (ROS), the product of
      mitochondrial oxidative metabolism. The aim of this study was to seek further
      evidence in support of this postulate, namely to test whether the levels of CAA
      and CHP correlate with cells metabolic activity. MATERIALS & METHODS: Peripheral
      blood lymphocytes are non-cycling (G(0)) cells characterized by minimal rate of
      oxidative metabolism. A dramatic rise in transcriptional and translational
      activity, an increase in number of mitochondria, and induction of DNA
      replication, occur during their mitogenic stimulation. This classic model of cell
      activation was chosen to study a possible correlation between CAA and CHP versus
      metabolic activity and generation of ROS. RESULTS: The levels of CAA and CHP in
      lymphocytes were increased many-fold during their stimulation. This increase was
      paralleled by the rise in extent of endogenously generated ROS. The growth of
      stimulated lymphocytes in the presence glucose antimetabolite 2-deoxy-D-glucose
      led to markedly lowered translational activity, decreased ROS generation and
      correspondingly attenuated CHA and CAA. CONCLUSIONS: The present data are
      consistent with our postulate that CHP and CAA report DNA damage by endogenous
      oxidants whose level correlates with metabolic activity. Because cumulative DNA
      damage by ROS generated via oxidative metabolism is considered the key mechanism
      responsible for cell ageing and senescence the data imply that these processes
      are delayed in G(0) quiescent lymphocytes or stem cells as compared with
      proliferating cells.

PMID- 17227293
TI  - Varying responses of human cells with discrepant p53 activity to ionizing
      radiation and heat shock exposure.
AB  - OBJECTIVES: Both heat shock (HS) and ionizing radiation have an impact on the
      cell cycle and may induce cell cycle arrest or apoptosis. Mutations of the p53
      gene are observed at a high frequency in human tumours and are recognized in
      about half of all human cancers. Sensitivity to radiation, heat and anticancer
      agents has been observed in p53(+/+) cells, but not in mutated or p53-deficient
      cells. Moreover, enhancement of radiosensitivity by HS has been observed in wild
      type p53 cells but not in p53-deficient cells. The molecular mechanism of the
      differential cell response to HS or ionizing radiation is not yet understood.
      MATERIALS AND METHODS: Differences in cellular response to radiation (200 kV X
      ray, 1, 2, 5 Gy) and HS (39 degrees C, 41 degrees C and 43 degrees C for 30 min)
      on cell cycle progression of cultures of human p53 mutant cells were investigated
      by flow cytometry. In addition, the effects of stressors used on the expression
      of several heat shock genes (HSP27, HSP60, HSP70, HSC70, HSP75, HSP78, HSP90)
      were studied by reverse transcriptase-polymerase chain reaction. RESULTS AND
      CONCLUSIONS: Yet, with respect to HSP gene expression, different stressors
      produced similar effects. Combination of HS and radiation treatment significantly
      induced the transcription of the HSP70 gene above the level induced by each
      stressor alone. Cell cycle analysis, however, revealed striking differences in
      prolonged dynamics of cell division in response to each stressor. Thus, p53
      status could be a useful indicator in predictive assays for hyperthermia cancer
      treatment in combination with radiation and/or chemotherapy.

PMID- 17227294
TI  - Photodynamic therapy combined with a cysteine proteinase inhibitor
      synergistically decrease VEGF production and promote tumour necrosis in a rat
      mammary carcinoma.
AB  - OBJECTIVES: Photodynamic therapy (PDT) and inhibition of cathepsin B proteases by
      cystatin (cysteine proteinase inhibitor, CPI) are potential new tumour treatment
      modalities. We have investigated the efficacy of PDT and CPI alone and in
      combination on a solid mammary carcinoma transplanted into Wistar rats. MATERIALS
      AND METHODS: Intraperitoneally injected single doses of chlorine e6 or HpD as
      photosensitizers were excited at 630 nm (90 J/cm(2)). CPI (500 micro g per
      animal) was injected around the tumour daily during the 8-day treatment.
      Inoculation of tumour was either on day 1 of the protocol, or 8 days before. On
      day 8, tumour size was measured, tumour necrosis and vascularization were
      determined based on haematoxylin and eosin (H&E)-stained sections and serum
      vascular endothelial growth factor (VEGF) levels measured using an enzyme-linked
      immunosorbent assay kit. RESULTS: No differences (two-way anova) were found for
      treatments started with various time lags. At doses where CPI or PDT alone had no
      or negligible effect, their combination caused a marked (P < 0.001) decrease in
      serum VEGF, paralleled by a significant decrease in tumour size and number of
      capillary vessels, and a significant increase in necrosis (up to 80% of the
      tumour tissue). CONCLUSIONS: The combination of PDT and CPI could be a useful
      approach in tumour therapy as the two agents appear to be synergistic and
      probably decrease VEGF production by the tumour tissue.

PMID- 17227295
TI  - Pharmacodynamics of T-cell function for monitoring immunosuppression.
AB  - OBJECTIVES: Recent studies show that measuring pharmacodynamic (PD) effects
      offers a unique possibility to predict immunosuppression. Thus, in this study we
      have monitored the PD properties of immunosuppressants on diverse T-cell
      functions in heart transplant (HTx) recipients. MATERIALS: PDs and blood
      concentrations (PK) of three different basis-immunosuppressive drugs were
      studied: cyclosporin A (CsA); tacrolimus (TRL) and sirolimus (SRL). T-cell
      function was analysed by expression of proliferating cell nuclear antigen (PCNA)
      labelling, expression of cytokines (IL-2, IFN-gamma) and surface antigen (for
      example, CD25) by FACS analysis. RESULTS: In group I, at time points C0 and C2,
      increased CsA-PK significantly inhibited expression of IL-2, IFN-gamma, PCNA and
      CD25 (P < 0.05). Correlations (r(2)) at C2 between inhibition of T-cell functions
      (PD) with PK and with drug doses were: CsA-PK: 0.71-0.91 and CsA-dose: 0.73-0.87.
      In group II, increased TRL-PK over time did not further inhibit expression of
      CD25, but inhibited PCNA expression more on day 3, and IL-2 and IFN-gamma
      expression was significantly higher on days 2 and 3 compared to PD effects of CsA
      (P < 0.05). Blood SRL concentrations in C0 group III, increased on day 1 and
      remained stable at days 3 and 4. Expression of PCNA was not altered in the SRL-PK
      category, whereas expression of CD25 was higher and expression of cytokines was
      lower than PD effects of CsA. CONCLUSIONS: Our results show that PD effects on T
      cell function can be used to monitor immunosuppression bringing potential to
      increase the efficacy and safety of immunosuppressive therapy after HTx.

PMID- 17227296
TI  - Spontaneous cell proliferation is associated with poor sensitivity to
      glucocorticoids in patients infected with HTLV.
AB  - BACKGROUND: Human T-cell lymphotropic viruses (HTLV)-I/II have a special tropism
      for infecting T cells and inducing spontaneous lymphocyte proliferation.
      Leukaemia and neurological manifestations are associated with HTLV-I/II
      infections, and treatment is usually based on anti-inflammatory drugs including
      glucocorticoids. Although steroid resistance has been reported, it is unknown
      whether this condition is related to the infection itself or to the treatment.
      OBJECTIVE: We investigated whether spontaneous cell proliferation is associated
      with T-cell sensitivity to glucocorticoids. MATERIALS AND METHODS: Twenty-eight
      HTLV-I/II patients and 11 healthy age-matched controls took part in this study.
      Lymphocytes were isolated and cultured in vitro to measure spontaneous and
      mitogen-induced proliferation as well as cellular sensitivity to dexamethasone.
      RESULTS: Patients with HTLV-I/II infection showed similar stimulated and
      unstimulated T-cell proliferation as well as comparable sensitivity to
      dexamethasone in vitro. There were no group differences in the frequency of
      glucocorticoid responders versus non-responders. However, T cells of patients
      with spontaneous proliferation were unresponsive to mitogenic stimulation and
      were remarkably more resistant to dexamethasone than cells of patients with
      normal proliferation. CONCLUSION: These data suggest that the poor clinical
      response to steroids may be associated with spontaneous cell proliferation during
      HTLV infection.

PMID- 17227297
TI  - Human amniotic fluid-derived stem cells have characteristics of multipotent stem
      cells.
AB  - OBJECTIVES: To characterize mesenchymal stem cell-like cells isolated from human
      amniotic fluid for a new source of therapeutic cells. MATERIALS: Fibroblastoid
      type cells obtained from amniotic fluid at the time of birth. METHODS: The
      ability of ex vivo expansion was investigated until senescence, and stem cell
      like characteristics were analyzed by examining differentiation potential,
      messenger RNA expression and immunophenotypes. RESULTS AND CONCLUSIONS: A
      morphologically homogenous population of fibroblastoid-type (HAFFTs) cells,
      similar to mesenchymal stem cells from bone marrow (BM-MSCs), was obtained at the
      third passage. The cells became senescent after 27 passages over a period of 8
      months while undergoing 66 population doublings. Under appropriate culture
      conditions, by the 8th passage they differentiated into adipocytes, osteocytes,
      chondrocytes and neuronal cells, as revealed by oil red O, von Kossa, Alcian blue
      and anti-NeuN antibody staining, respectively. Immunophenotype analyses at the
      17th passage demonstrated the presence of TRA-1-60; SSEA-3 and-4; collagen types
      I, II, III, IV and XII; fibronectin; alpha-SMA; vimentin; desmin; CK18; CD44;
      CD54; CD106; FSP; vWF; CD31; and HLA ABC. Reverse transcriptase-polymerase chain
      reaction analysis of the HAFFTs from passages 6-20 showed consistent expression
      of Rex-1, SCF, GATA-4, vimentin, CK18, FGF-5 and HLA ABC genes. Oct-4 gene
      expression was observed up to the 19th passage but not at the 20th passage.
      HAFFTs showed telomerase activity at the 5th passage with a decreased level by
      the 21st passage. Interestingly, BMP-4, AFP, nestin and HNF-4alpha genes showed
      differential gene expression during ex vivo expansion. Taken together, these
      observations suggest that HAFFTs are pluripotent stem cells that are less
      differentiated than BM-MSCs, and that their gene expression profiles vary with
      passage number during ex vivo expansion.

PMID- 17227298
TI  - Generation of somatic cell hybrids for the production of biologically active
      factors that stimulate proliferation of other cells.
AB  - OBJECTIVE: Some normal somatic cells in culture divide a limited number of times
      before entering a non-dividing state called replicative senescence and fusion of
      normal cells with immortal cells claimed to produce hybrid cells of limited
      proliferation. We reinvestigated the proliferative capacity of hybrid cells
      between normal cell and immortal cell. MATERIALS AND METHODS: Normal pig
      fibroblast cells and cells of immortal mouse fibroblast cell line F7, a
      derivative of GM05267, were fused by polyethylene glycol treatment and
      subsequently the fused cells were cultured in a selective medium containing
      hypoxanthine-aminopterin-thymidine in order to enrich the hybrid cells. The
      hybrid cells were then monitored for chromosome content and proliferation.
      RESULTS: Cytogenetic analysis revealed that the hybrid cells contained polyploidy
      chromosomes derived from normal pig fibroblasts. These hybrid cells exhibit no
      sign of replicative senescence after more than 190 population doublings in vitro.
      Instead, these hybrid cells have an accelerated growth and proliferate even in
      the complete absence of glutamine. In addition, these hybrids produce
      biologically active factors in the conditioned media, which not only can
      accelerate their own proliferation but also can reinitiate mitotic activity in
      the senescent-like normal fibroblast cells. CONCLUSIONS: Our results question the
      validity of cellular senescence as a dominant trait. Additionally, the generation
      of hybrid cells using the specific mouse cell line can be applied to the
      generation of hybrids with other normal cell types and can be used to produce
      tissue-specific growth-factor(s) to extend the lifespan and/or improve the
      proliferation of various normal cells, including adult stem cells.

PMID- 17227299
TI  - Simulating mouse mammary gland development: cell ageing and its relation to stem
      and progenitor activity.
AB  - BACKGROUND: Somatic stem and progenitor cell division is likely to be an
      important determinant of tumor development. Each division is accompanied by a
      risk of fixing genetic mutations, and/or generating innately immortal cells that
      escape normal physiological controls. AIM: Using biological information, we aimed
      to devise a theoretical model for mammary gland development that described the
      effect of various stem/progenitor cells activities on the demographics of adult
      mammary epithelial cell populations. RESULTS: We found that mammary ductal trees
      should develop in juvenile mice despite widely variant levels of activity in the
      progenitor compartment. Sequestration (inactivation) of progenitor cells
      dramatically affected the aging-maturation of the population without affecting
      the total regenerative capacity of the gland. Our results showed that if stem and
      progenitor cells can be demonstrated in glands regenerated by serial
      transplantation, they originated in a canonical primary stem cell (providing a
      functional definition of mammary stem cells). Finally, when the probability of
      symmetric division of stem cells increased above a threshold, the mammary
      epithelial population overall was immortal during serial transplantation.
      CONCLUSIONS: This model provides, (1) a theoretical framework for testing whether
      the phenotypes of genetically modified mice (many of which are breast cancer
      models) derive from changes of stem and progenitor activity, and (2) a means to
      evaluate the resolving power of functional assays of regenerative capacity in
      mammary epithelial cell populations.

PMID- 17227300
TI  - Nicotine-induced proliferation of isolated rat pancreatic acinar cells: effect on
      cell signalling and function.
AB  - OBJECTIVES: The aim of the current study was to investigate whether nicotine
      treatment would induce the proliferation of isolated rat primary pancreatic
      acinar cells in culture by activating mitogen-activated protein kinase (MAPK)
      signalling and exocrine secretion. MATERIALS AND METHODS: A nicotine dose- and
      time-response curve was initially developed to determine the optimal dose and
      time used for all subsequent studies. Proliferation studies were conducted by
      cell counting and confirmed further by bromodeoxyuridine (BrdU) incorporation and
      flow cytometry assays. MAPK signalling studies were conducted by Western blot
      analysis. Localization of ERK1/2 signals, with or without nicotine and the MAPK
      inhibitor, was visualized by immunofluorescence. RESULTS: Nicotine treatment
      caused dose-dependent activation of extracellular signal-regulated kinases
      (ERK1/2), the maxima occurring at 100 micro m and at 3 min after treatment; the
      response was suppressed by the ERK1/2 inhibitor. Maximal nicotine-induced cell
      proliferation occurred at 24 h, and UO126-treatment significantly reduced this
      response. Exposure of cells to 100 microm nicotine for 6 min significantly
      enhanced both baseline and cholecystokinin-stimulated cell function, and these
      effects were not affected by treatment with the inhibitor of ERK1/2 but were
      suppressed by mecamylamine, a nicotinic receptor antagonist. CONCLUSIONS: Our
      results suggest that nicotine treatment induced cell proliferation of isolated
      pancreatic acinar cells and that this is coupled with the activation of MAPK
      signalling with no effect on its function. Hence, in primary cells, the mechanism
      of induction and regulation of these two processes, cell proliferation and cell
      function, by nicotine treatment are independent of each other.

PMID- 17227302
TI  - Eosinophilic esophagitis: an update.
AB  - Eosinophilic esophagitis (EE) is a disease that is being recognized with
      increasing frequency. In children it is responsible for feeding disorders,
      vomiting, reflux symptoms and abdominal pain and in adults it causes dysphagia
      and esophageal food impactions. The diagnosis requires the histologic finding of
      > 20 eosinophils per high powered field in esophageal squamous mucosa. The most
      common treatment regimens in children and adults involve the ingestion of topical
      corticosteroids. Symptomatic relapse after one treatment course is common, and
      many patients require repeated courses of treatment. The long-term prognosis of
      EE is largely unknown.

PMID- 17227303
TI  - Lack of EGFR gene mutations in exons 19 and 21 in esophageal (Barrett's)
      adenocarcinomas.
AB  - Epidermal growth factor receptor is over-expressed in several tumors and is the
      target for the tyrosine kinase inhibitor gefitinib. This receptor is also over
      expressed in esophageal adenocarcinomas. In non-small cell lung cancer, specific
      somatic mutations residing in the epidermal growth factor receptor tyrosine
      kinase in the activation loop and the glycine-rich P-loop, are responsible for an
      enhanced sensitivity toward gefitinib. We analyzed exons 19 and 21 coding for the
      receptor tyrosine kinase of the epidermal growth factor gene in 105 samples of
      esophageal (Barrett's) adenocarcinoma by denaturing high-pressure liquid
      chromatography. We found only one silent mutation in exon 19 of adenine to
      guanine in codon 754 leading to a substitution of K to K, the rest of the sample
      being wild-type genotype. In conclusion, mutations within the tyrosine kinase
      domain of EGFR associated with sensitivity of non-small cell lung cancer patients
      to gefitinib are not present in esophageal (Barrett's) adenocarcinoma.

PMID- 17227304
TI  - Concurrent chemoradiation for patients with squamous cell carcinoma of the
      cervical esophagus.
AB  - Little is known concerning the role of concurrent chemoradiation (CCRT) in the
      management of carcinoma of the cervical esophagus. We retrospectively evaluated
      our treatment approach for patients with cervical esophageal cancer with special
      emphasis on CCRT with or without surgery. Medical records of 21 consecutive
      patients with cervical esophageal carcinoma treated mainly with CCRT (1997-2004)
      were reviewed, and factors that influenced patient survival were analyzed
      retrospectively. Nineteen received CCRT with cisplatin/5-fluorouracil and five
      underwent curative surgery. Two patients who were deemed unfit for CCRT received
      radiation therapy alone. All had three-dimensional treatment planning (median
      total dose, 40 Gy with surgery, 64 Gy without surgery). Of the 19 patients who
      received CCRT, 11 patients including five who underwent curative surgery achieved
      initial local control. Neither of the two patients who received radiation therapy
      alone achieved local control. Among 19 patients who underwent CCRT, 9/11 with T1
      3 grade tumors achieved initial local control, but only 2/8 patients with T4
      tumors (P = 0.011, chi(2) test) achieved initial local control. No patient
      without initial local control survived > 20 months compared with 2-year and 5
      year survival rates of 60% and 40% in those who achieved initial local control (P
      = 0.038). No patient with T4 tumors survived > 18 months, whereas 2- and 5-year
      survival rates were 62% and 41%, respectively, in those with T1-3 tumors (P =
      0.006). The significant effect of T-classification on survival was maintained
      when analyzed among 19 patients who received CCRT. CCRT shows promise for
      cervical esophageal carcinoma. T-classification and initial local control had
      significant impact on survival.

PMID- 17227306
TI  - Predictive factors associated with prolonged chest drain production after
      esophagectomy.
AB  - After esophagectomy, pleural drainage is performed to ensure complete drainage of
      the pleural cavities. The aim of this study was to detect predisposing factors
      for prolonged drainage. Patients who underwent transhiatal or extended
      transthoracic esophagectomy for adenocarcinoma of the distal esophagus or
      gastroesophageal junction were included. Patients who underwent esophagectomy
      produced a median total drainage volume of 2477 mL (range 30-14,908). Seventy
      five patients needed chest drainage = 7 days (short drainage) while 57 patients
      needed chest drainage > 7 days (prolonged drainage). Factors associated with
      prolonged drainage were a transthoracic approach (P < 0.001), a higher volume of
      blood loss (P = 0.027), a higher number of resected lymphnodes (P = 0.046) and a
      radical dissection (P = 0.033). Prolonged pleural drainage is associated with a
      transthoracic approach and is seen more often in patients after a microscopically
      radical dissection. Prolonged drainage is a sign of adequate dissection on the
      site of the primary tumor, probably due to the more extensive trauma to the
      lymphatic vessels in the mediastinum.

PMID- 17227305
TI  - Transabdominal ligation of the thoracic duct as treatment of choice for
      postoperative chylothorax after esophagectomy.
AB  - Postoperative chylothorax after injury of the thoracic duct during esophagectomy
      is a rare but severe complication which may lead to serious problems such as loss
      of fat and proteins, and immunodeficiency. Without treatment mortality can rise
      to over 50%. From 1988 to 2005, we treated 10 patients with postoperative
      chylothorax after 409 resections of the esophagus (2.4%). Of these 10 patients
      nine underwent transthoracic esophagectomy with gastric pull-up to enable an
      intrathoracic (n = 7) or cervical (n = 2) anastomosis and one patient received a
      transhiatal esophagectomy with gastric pull-up and cervical anastomosis. The
      average amount of postoperative chylus was 2205 mL (200-4500 mL) per day. After a
      median postoperative interval of 10 days, relaparotomy and transhiatal double
      ligation of the thoracic duct was performed in nine out of 10 patients. One
      patient could be managed conservatively. The average amount of chylus was reduced
      to 151 mL per day (90.5%). Seven patients had no complications, and three
      suffered from postoperative pneumonia. Two of the patients with pneumonia
      recovered, and one died. Discharge from hospital, after ligation of the thoracic
      duct, was possible after a median time of 18 days (11-52). Ligation of the
      thoracic duct via relaparotomy appeared to be a simple and safe method to treat
      postoperative chylothorax.

PMID- 17227307
TI  - Prognostic significance of body mass indices for patients undergoing
      esophagectomy for cancer.
AB  - The aim of this study was to determine the role of body mass index (BMI) in a
      Western population on outcomes after esophagectomy for cancer. Two hundred and
      fifteen consecutive patients undergoing esophagectomy for esophageal cancer of
      any cell type were studied prospectively. Patients with BMIs > 25 kg/m were
      classified as overweight and compared with control patients with BMIs below these
      reference values. Ninety-seven patients (45%) had low or normal BMIs, 86 patients
      (40%) were overweight, and a further 32 (15%) were obese. High BMIs were
      associated with a higher incidence of adenocarcinoma versus squamous cell
      carcinoma (83%vs. 14%, P = 0.041). Operative morbidity and mortality were 53% and
      3% in overweight patients compared with 49% (P = 0.489) and 8% (P = 0.123) in
      control patients. Cumulative survival at 5 years was 27% for overweight patients
      compared with 38% for control patients (P = 0.6896). In a multivariate analysis,
      age (hazard ratio [HR] 1.492, 95% CI 1.143-1.948, P = 0.003), T-stage (HR 1.459,
      95% CI 1.028-2.071, P = 0.034), N-stage (HR 1.815, 95% CI 1.039-3.172, P = 0.036)
      and the number of lymph node metastases (HR 1.008, 95% CI 1.023-1.158, P =
      0.008), were significantly and independently associated with durations of
      survival. High BMIs were not associated with increased operative risk, and long
      term outcomes were similar after R0 esophagectomy.

PMID- 17227308
TI  - Is intestinal metaplasia a necessary precursor lesion for adenocarcinomas of the
      distal esophagus, gastroesophageal junction and gastric cardia?
AB  - Adenocarcinoma of the distal esophagus and gastroesophageal junction are believed
      to arise in Barrett's esophagus with intestinal metaplasia. Whether
      adenocarcinoma can arise in columnar lined esophagus without intestinal
      metaplasia is in doubt. Whether adenocarcinoma of the gastric cardia arises in
      intestinal metaplasia of the gastric cardia is also in doubt. We aim to evaluate
      the relationship of size and stage of adenocarcinoma of the distal esophagus,
      gastroesophageal junction and gastric cardia to intestinal metaplasia and other
      types of columnar epithelium. Seventy-four patients who had esophagogastrectomy
      for adenocarcinomas in this region were examined histologically to assess the
      frequency of residual intestinal metaplasia in the surrounding epithelium. Tumors
      without residual intestinal metaplasia were evaluated for the presence of other
      columnar epithelia and correlated with tumor size and stage. Cardiac mucosa was
      present around all tumors. Residual intestinal metaplasia was present in 48 (65%)
      tumors, including 33/38 (87%) distal esophageal, 10/25 (45%) junctional and 5/11
      (45%) gastric cardia tumors. The prevalence of intestinal metaplasia was 100% in
      all tumors that were less than 1 cm in maximum diameter and all intramucosal
      tumors. The prevalence of residual intestinal metaplasia decreased with
      increasing tumor size and stage. These data strongly support the contention that
      adenocarcinomas of this region, including those in the gastric cardia, arise in
      intestinal metaplastic epithelium. The absence of residual intestinal metaplasia
      in larger tumors is the result of tumor overgrowing the intestinal metaplasia
      from which it arose.

PMID- 17227309
TI  - Sound spectrogram analysis in patients receiving Kawahara's surgical voice
      restoration for advanced carcinoma of the hypopharynx and cervical esophagus.
AB  - Loss of voice after total laryngectomy is a major concern that has prompted much
      effort to develop methods of surgical voice restoration. In 1992, Kawahara
      described a tracheocolic shunt for voice restoration using a revascularized
      ileocolic graft. With this method, aspiration through the phonatory shunt is
      prevented by the ileocolic valve (Bauhin's valve), while vocalization is allowed.
      The purpose of this study was to use sound spectrogram analysis to evaluate
      voices surgically restored in that way. Between 2002 and 2005, 10 consecutive
      patients underwent laryngopharyngoesophagectomy with Kawahara's surgical voice
      restoration for advanced carcinoma of the hypopharynx and/or cervical esophagus
      at Akita University Hospital, Japan. We then used sound spectrography to analyze
      and compare the voices of patients receiving Kawahara's voice restoration,
      against healthy volunteers and patients who underwent the same surgery without
      voice restoration and spoke using an electronic larynx. We also evaluated the
      intelligibility of conversation and performed a listening test. The sound
      spectrograms showed that when produced by the electronic larynx, consonant sounds
      and voice frequencies below 300 Hz were not clearly recognized. By contrast, in
      patients who received Kawahara's surgical voice restoration, consonant and vowel
      sounds at frequencies above and below 300 Hz were clearly recognized. Although
      conversation was intelligible with both Kawahara's surgical voice restoration and
      the electronic device, listeners judged the voice produced by the former to be
      superior. Thus, the voice produced by Kawahara's surgical voice restoration is
      superior to that produced by the electronic larynx.

PMID- 17227310
TI  - When are reflux episodes symptomatic?
AB  - Careful scrutiny of pH recordings and symptom diaries in patients having 24-hour
      pH-metry reveals that most reflux episodes are asymptomatic. Although this
      observation is well known and long recognized, the explanation for why one reflux
      episode leads to symptoms and others do not is incompletely understood. Forty
      four patients with chronic typical gastroesophageal reflux disease (GERD)
      symptoms referred for ambulatory pH testing were studied. Antisecretory
      medication was stopped 2 weeks prior to the study. Two meals were taken during
      the study; one standardized (hamburger, fries, milk-shake) and one at the
      patient's discretion. A system onset marker noted the type, beginning and end of
      symptoms (heartburn, regurgitation, chest pain). Age, sex, upright/supine
      position, nadir pH, time pH < 4, and relationship to meals were compared for
      symptomatic/asymptomatic reflux episodes. An acid reflux event was defined as a
      drop in pH < 4 lasting > 5 seconds. The pH catheter detected 1464 reflux
      episodes. Only 93 (6.3%) were symptomatic. Forty-six of the 93 (49.4%) were
      associated with heartburn, 38 (40.9%) with regurgitation, and nine (9.7%) with
      chest pain. Nadir pH was significantly lower in symptomatic episodes. Nearly 50%
      of symptomatic reflux episodes occurred after meals, especially after non
      standardized compared to standardized meal. Symptomatic episodes tended to be
      longer in duration and to occur in the supine position, while age/sex made no
      difference. Six percent of the reflux episodes were temporally associated with
      typical GERD symptoms. This association seems to be influenced by the acidity of
      the refluxate. Nearly half of the symptomatic reflux episodes occurred after
      eating.

PMID- 17227311
TI  - Familial trends of inheritance in gastro esophageal reflux disease, Barrett's
      esophagus and Barrett's adenocarcinoma: 20 families.
AB  - We reported four families with familial Barrett's esophagus (FBE) in 1993. This
      follow-up study includes an additional 16 families with FBE, gastroesophageal
      reflux disease (GERD) and BE-related adenocarcinoma (BEAC) highlighting the
      familial trends of inheritance. A retrospective survey of endoscopic and
      histopathological reports on 95 confirmed cases of BE from 1975 to 2005 was
      performed and a detailed family history was obtained. Five representative
      pedigrees from a total of 20 are discussed here. These 20 families represent one
      of the largest cohorts studied over three decades from a single institution.
      Familial BE is more common than previously thought and the prevalence of GERD, BE
      and BEAC in these families is distinctly higher than with sporadic cases. The
      conditions appear to be inherited in an autosomal dominant fashion with
      incomplete penetrance. Hence diligence in taking family history with BE patients
      is critical since the endoscopic screening of relatives is warranted in FBE.
      Earlier diagnosis and surveillance of FBE should hopefully improve outcomes.

PMID- 17227312
TI  - The lower esophageal sphincter strength in patients with gastroesophageal reflux
      before and after laparoscopic Nissen fundoplication.
AB  - Lower esophageal sphincter pressure (LESP) and sphincter strength (LESS) were
      measured before and after short and floppy laparoscopic Nissen fundoplication
      (LNF) in 38 patients with severe gastro-esophageal reflux disease (GERD). These
      patients were compared with a control group of 23 healthy volunteers. GERD was
      assessed by stationary manometry, 24-h pH recordings and endoscopy. LESS was
      verified by motorized pull-back of an air-filled balloon catheter from the
      stomach into the esophagus. The catheter assembly was well tolerated by all study
      participants. LESP increased significantly after operation from 8 mmHg to 14 mmHg
      (75% of normal values; P < 0.0001), but compared to the control group, LESP (22
      mmHg) decreased significantly (P < 0.002). In the control group and in patients
      with GERD, LESP and LESS showed excellent correlation (r = 0.97, r = 0.94,
      respectively). After LNF, LESS increased significantly from 0.6 to 1.6 N (P <
      0.0001), about 166%. We conclude that the measurement of LESS is able to explain
      the discrepancy between satisfactory NF operation and the distinct increase of
      postoperative LESP. The evaluation of LESS is a helpful tool in assessing
      functional understanding of laparoscopic Nissen fundoplication with a short and
      floppy wrap.

PMID- 17227313
TI  - The effect of laparoscopic partial fundoplication on dysphagia, esophageal and
      lower esophageal sphincter motility.
AB  - It has been suggested that dysphagia is less common after partial versus complete
      fundoplication. The mechanisms contributing to postoperative dysphagia remain
      unclear. The objective of the present prospective study was to investigate
      esophageal motility and the prevalence of dysphagia in patients who have
      undergone laparoscopic partial fundoplication. Symptoms, lower esophageal
      sphincter (LES) characteristics and esophageal body motility were evaluated
      prospectively in 62 patients before and after laparoscopic partial
      fundoplication: 33 women and 29 men with a mean age of 44 +/- 1.5 years (range,
      21-71). The patients filled in symptom questionnaires and underwent stationary
      and ambulatory manometry and 24-h pH-metry before and after operation. A small
      but significant increase in LES pressure from 14.8 +/- 0.9 to 17.8 +/- 0.8 mmHg
      was seen after laparoscopic partial fundoplication. Further, LES characteristics
      and esophageal body motility were not different post- versus preoperation. Three
      months after surgery, dysphagia was present in eight patients. No differences in
      LES characteristics or body motility were present between patients with and
      without dysphagia. Six months after the operation dysphagia was present in only
      three patients (3.2% mild and 1.6% severe dysphagia). Adequate reflux control was
      obtained in 85% of the patients. Laparoscopic partial fundoplication offers
      adequate reflux control without affecting esophageal body motility and with a
      very low incidence of postoperative dysphagia.

PMID- 17227314
TI  - Trans-cutaneous electrogastrographic study of gastric myoelectric activity in
      transposed intrathoracic stomach after esophagectomy.
AB  - We examined the feasibility of trans-cutaneous electrogastrography (EGG) in
      recording myoelectric activity of the transposed thoracic stomach after
      esophagectomy. Nineteen patients who had Ivor-Lewis esophagectomy were studied.
      The EGG signal was recorded using cutaneous electrodes placed over the lower
      sternum. Eleven patients who underwent total gastrectomy served as controls.
      Normal rhythm pattern (2.4-3.6 cpm > or = 70%) and power ratio (PR > or = 2) was
      observed in five and 12 patients, respectively, after esophagectomy. The
      observation of normal gastric rhythm was more frequent in the postprandial period
      in the esophagectomy group (median 42.6%vs. 7.4%, P = 0.01), and the PR was
      significantly higher (median 2.27 vs. 1.38, P = 0.013) than the gastrectomy
      group. Feeding further increased the prevalence of normal gastric slow wave in
      the esophagectomy group (median 14.8% to 42.6%, P = 0.002) and improved the
      stability of dominant frequency (median 78% to 67%, P = 0.015). We conclude that
      gastric myoelectric activities of thoracic transposed stomach can be detected
      from cutaneous sternal electrodes. This represented a preservation of gastric
      motility even when the stomach is pulled up to the thorax as a substitute for the
      esophagus.

PMID- 17227315
TI  - Squamous cell carcinoma and Zenker diverticulum.
AB  - Squamous cell carcinoma in a Zenker diverticulum is a very rare condition. We
      report a case of a patient with a Zenker carcinoma, who was primarily
      functionally inoperable and therefore received neoadjuvant radiochemotherapy
      before cardiac bypass surgery. After a complicated course with cardiogenic shock
      and myocardial infarction, a re-evaluation of functional risk analysis and the
      tumor situation revealed operability. Subsequently, partial hypopharyngectomy and
      partial cervical esophageal resection with lymphadenectomy was performed.
      Reconstruction of the gastrointestinal continuity was made by interposition of a
      free small bowel graft and microvascular anastomosis. The postoperative course
      showed a small anastomotic leakage of the hypopharyngeal-small bowel anastomosis,
      which was successfully treated conservatively.

PMID- 17227316
TI  - Surgical resection of solitary adrenal metastasis from esophageal carcinoma
      following esophagectomy.
AB  - The prognosis of esophageal carcinoma following esophagectomy is poor due to a
      high frequency of metastasis to periesophageal lymph nodes and distant organs.
      However, we experienced a case with good prognosis following resection of a
      solitary adrenal metastatic tumor. The patient was a 70-year-old man diagnosed
      with type 2 esophageal cancer (Lt-Ae, T2N1M0, Stage IIB) who was treated with
      esophagectomy. Eight months following surgery, solitary adrenal metastasis was
      detected by CT, and was resected. At 42 months follow-up he has had a good
      quality of life in the community without evidence of recurrence. To the best of
      our knowledge, only five cases with resected solitary adrenal metastases
      including our case, have been reported, and show a greater than 1-year survival.
      Consequently, we suggest that resection of solitary organ metastases is a good
      alternative, even following esophagectomy.

PMID- 17227317
TI  - Non-alcoholic fatty liver disease, the metabolic syndrome and the risk of
      cardiovascular disease: the plot thickens.
AB  - Non-alcoholic fatty liver disease (NAFLD) affects a substantial proportion of the
      general population and is frequently associated with many features of the
      metabolic syndrome (MetS). Currently, the importance of NAFLD and its
      relationship with the MetS is being increasingly recognized, and this has
      stimulated an interest in the possible role of NAFLD in the development of
      atherosclerosis. Recent studies have reported the association of NAFLD with
      multiple classical and non-classical risk factors for cardiovascular disease
      (CVD). Moreover, there is a strong association between the severity of liver
      histopathology in NAFLD patients and greater carotid artery intima-media
      thickness and plaque, and lower endothelial flow-mediated vasodilation (as
      markers of subclinical atherosclerosis) independent of obesity and other MetS
      components. Finally, it has recently been demonstrated that NAFLD is associated
      with an increased risk of all-cause death and predicts future CVD events
      independently of other prognostic factors, including MetS components. Overall,
      therefore, the evidence from these recent studies strongly emphasizes the
      importance of assessing the global CVD risk in patients with NAFLD. Moreover,
      these novel findings suggest a more complex picture and raise the possibility
      that NAFLD, as a component of the MetS, might not only be a marker but also an
      early mediator of CVD.

PMID- 17227318
TI  - The UK Diabetes Research Network--an opportunity and a challenge.
AB  - The Department of Health has funded a national diabetes network to support
      clinical research. The network will facilitate recruitment into clinical trials
      and has been widely welcomed by clinicians. However, if the network is to reach
      its full potential, all those involved will need to advocate a change in attitude
      towards clinical trials and research, encouraging participation and contribution
      of data. Clinicians need to be willing to take a proactive view about research
      studies, and to encourage patients to adopt a positive and altruistic attitude
      towards trial participation. The future of trials and other important clinical
      research in the UK may depend on it.

PMID- 17227319
TI  - All-cause and cardiovascular mortality in diabetic subjects increases
      significantly with reduced estimated glomerular filtration rate (eGFR): 10 years'
      data from the South Tees Diabetes Mortality study.
AB  - AIMS: To investigate the association between estimated glomerular filtration rate
      (eGFR) and total and cardiovascular mortality in a population-based cohort of
      diabetic subjects. METHODS: A longitudinal study using a population-based
      district diabetes register comprising 3288 subjects in South Tees, UK. The eGFR
      was calculated using the Modification of Diet in Renal Disease (MDRD) study
      equation. Patients were stratified by baseline eGFR into five stages as per the
      National Kidney Foundation guidelines: Stage 1, eGFR > 90; Stage 2, eGFR 60-89;
      Stage 3, eGFR 30-59; Stage 4, eGFR 15-29; and Stage 5, eGFR < 15 ml/min per 1.73
      m(2). Main outcome was all-cause and cardiovascular mortality between 1 January
      1994 and 31 July 2004. RESULTS: At baseline, mean age (58.4 years) differed
      between groups. Persons with lower eGFR were older (P < 0.001). Thirty-six
      percent (n = 1193, males 56%) had died by 10 years (cardiovascular cause in 60%).
      Median follow-up was 10.5 years amounting to 28 342 person years. Stages 4 and 5
      (eGFR <or= 29 ml/min per 1.73 m(2)) were amalgamated for mortality analysis.
      Total and cardiovascular mortality increased with reduced eGFR. Adjusted hazard
      ratios (HR) [95% confidence interval (CI)] for all-cause mortality comparing
      groups 2 and 3, and 4 and 5 combined with group 1 were 1.28 (1.02, 1.60), 2.58
      (2.05, 3.25) and 6.42 (4.25, 9.71), respectively. Adjusted HRs (95% CI) for
      mortality due to circulatory disease comparing groups 2 and 3, and 4 and 5
      combined with group 1 were 1.50 (1.10, 2.06), 3.32 (2.41, 4.58) and 7.99 (4.69,
      13.62), respectively. CONCLUSIONS: In diabetic subjects, mortality increases
      significantly with reduced GFR. Low eGFR identifies patients at high risk of
      cardiovascular mortality who should be targeted for aggressive risk factor
      modification.

PMID- 17227320
TI  - Incipient cardiovascular autonomic imbalance revealed by wavelet analysis of
      heart rate variability in Type 2 diabetic patients.
AB  - AIM: Incipient cardiovascular autonomic imbalance is not readily diagnosed by
      conventional methods. Spectral analysis of heart rate variability (HRV) by
      wavelet transform (WT) was used to measure cardiovascular autonomic function in
      patients with Type 2 diabetes. METHODS: Thirty-two diabetic patients without (D),
      26 with cardiovascular autonomic neuropathy (DAN) and 72 control subjects (C)
      participated. A 30-min HRV time series was analysed by wavelet transformation and
      four characteristic frequency intervals were defined: I (0.0095-0.021 Hz), II
      (0.021-0.052 Hz), III (0.052-0.145 Hz) and IV (0.145-0.6 Hz). RESULTS: When
      compared with C, in both D and DAN the normalized power and amplitude of interval
      II were increased and of interval IV decreased, resulting in a significantly
      higher II/IV ratio. Furthermore, in DAN the normalized power and amplitude of
      interval I were increased and of interval III decreased when compared with the D
      and C groups. The diabetic patients were divided in two equal subgroups according
      to HbA(1c) < 8.0% and >or= 8.0%. In the subgroup with HbA(1c) >or= 8.0%,
      normalized power in interval II was significantly higher and in interval IV
      significantly lower than in the subgroup with HbA(1c) < 8.0%. In D, but not in
      DAN patients prescribed ACE inhibitors, the absolute amplitude and power of
      oscillations were significantly higher than in patients not taking ACE inhibitor
      therapy. CONCLUSIONS: Patients with diabetes have increased sympathetic and
      decreased parasympathetic cardiac activity regardless of the presence of
      autonomic neuropathy. Glycaemic control and treatment with ACE inhibitors may
      favourably influence HRV in diabetic patients without autonomic neuropathy.

PMID- 17227321
TI  - Insulin detemir compared with NPH insulin in children and adolescents with Type 1
      diabetes.
AB  - AIMS: This study compared the effect of insulin detemir on glycaemic control
      (HbA(1c), fasting plasma glucose and variability thereof) with that of Neutral
      Protamine Hagedorn human isophane (NPH) insulin, both combined with insulin
      aspart, in children with Type 1 diabetes mellitus, and compared the safety of
      these treatments. METHODS: In this 26-week, open-label, randomized (2 : 1),
      parallel-group study, 347 (140 prepubertal and 207 pubertal) children with Type 1
      diabetes, aged 6-17 years, received insulin detemir (n = 232) or NPH insulin (n =
      115) once or twice daily, according to the prestudy regimen, plus premeal insulin
      aspart. RESULTS: The mean HbA(1c) decreased by approximately 0.8% with both
      treatments. After 26 weeks, the mean difference in HbA(1c) was 0.1% (95%
      confidence interval -0.1, 0.3) (insulin detemir 8.0%, NPH insulin 7.9%). Within
      subject variation in self-measured fasting plasma glucose was significantly lower
      with insulin detemir than with NPH insulin (SD 3.3 vs. 4.3, P < 0.001), as was
      mean fasting plasma glucose (8.4 vs. 9.6 mmol/l, P = 0.022). The risk of
      nocturnal hypoglycaemia (22.00-07.00 h) was 26% lower with insulin detemir (P =
      0.041) and the risk of 24-h hypoglycaemia was similar with the two treatments (P
      = 0.351). The mean body mass index (BMI) Z-score was lower with insulin detemir
      (P < 0.001). CONCLUSIONS: Basal-bolus treatment with insulin detemir or NPH
      insulin and premeal insulin aspart in children and adolescents with Type 1
      diabetes mellitus improved HbA(1c) to a similar degree. The lower and more
      predictable fasting plasma glucose, lower risk of nocturnal hypoglycaemia and
      lower BMI observed with insulin detemir are clinically significant advantages
      compared with NPH insulin.

PMID- 17227323
TI  - Stability of an empirical psychosocial taxonomy across type of diabetes and
      treatment.
AB  - AIMS: The aims of the study were (i) to examine whether an empirical psychosocial
      taxonomy, based on key diabetes-related variables, is independent of type of
      diabetes and treatment, and (ii) to further establish the external validation of
      the taxonomy. METHODS: In a cross-sectional study, 82 patients with Type 1 and 86
      patients with Type 2 diabetes mellitus were assigned to one of three psychosocial
      patient profiles based on their Multidimensional Diabetes Questionnaire (MDQ)
      scores. General psychological and diabetes-specific measures were obtained
      through self-report and HbA(1c) was measured. RESULTS: Equal proportions of Type
      1 and Type 2 patients, and of patients using insulin and oral medication/diet
      only were classified within each of the three psychosocial profiles. External
      validation confirmed the validity and distinctiveness of the patients' profiles.
      The patient profiles were independent of demographic variables, body mass index,
      duration of diabetes, complexity of treatment, number of complications, social
      desirability, and major stress levels. CONCLUSIONS: The Psychosocial Taxonomy for
      Patients with Diabetes provides a new way to categorize individuals who may have
      more in common than just their type of diabetes and/or its treatment and can help
      target interventions to individual patients' needs.

PMID- 17227322
TI  - Magnetic resonance imaging: a reliable method for measuring pancreatic volume in
      Type 1 diabetes.
AB  - AIM: To validate magnetic resonance imaging (MRI) for monitoring pancreatic
      atrophy in Type 1 diabetes. METHODS: Twelve male patients with Type 1 diabetes of
      duration >or= 10 years (median age 28, range 19-32 years) and 12 healthy controls
      (median age 30, range 22-36 years) were invited for two abdominal MRI scans, 14
      days apart. Four sequences were used: standard T1-weighted; standard T2-weighted;
      volumetric interpolated breath-hold examination (VIBE); and T1-weighted breath
      hold with fat suppression (T1BHFS). The pancreas was identified on coded images
      by one observer and volumes estimated by interpolation. RESULTS: Eleven patients
      and all controls were scanned twice. Visualization of the pancreas was best with
      VIBE and T1BHFS, allowing volume estimation from 47 and 46 scans, respectively.
      The pancreatic volume of patients estimated from these sequences were half those
      of controls (52.4 ml, +/- 17.1 ml, mean +/- sd) vs. (101 ml, +/- 19.5 ml, P <
      0.001) and estimates showed little bias between visits; mean difference 1.1 ml
      (95% CI; -3.1 to 5.3 ml, P = 0.61) using VIBE and -2.6 ml (-5.8 to 0.6 ml, P =
      0.03) using T1BHFS. Both sequences gave similar precision; the standard deviation
      of the differences in volume estimates between visits was 9.7 ml for VIBE and 7.3
      ml for T1BHFS, although mean volumes estimated from T1BHFS were 4.9 ml lower (
      8.2 to -1.7 ml, P = 0.005). CONCLUSIONS: Pancreatic volume can be measured
      reliably using MRI and shows a 48% reduction in long-standing Type 1 diabetes as
      compared with age-matched normal subjects. MRI should prove useful in determining
      the natural history of pancreatic atrophy in diabetes.

PMID- 17227324
TI  - Association of diabetes-related emotional distress with diabetes treatment in
      primary care patients with Type 2 diabetes.
AB  - AIMS: To characterize the determinants of diabetes-related emotional distress by
      treatment modality (diet only, oral medication only, or insulin). METHODS: A
      total of 815 primary care patients with Type 2 diabetes completed the Problem
      Areas in Diabetes (PAID) Scale and other questions. We linked survey data to a
      diabetes clinical research database and used linear regression models to assess
      the associations of treatment with PAID score. RESULTS: PAID scores were
      significantly higher among insulin-treated (24.6) compared with oral-treated
      (17.8, P < 0.001) or diet-treated patients (14.7, P < 0.001), but not different
      between oral- vs. diet-treated patients (P = 0.2). Group scores remained similar,
      but the statistical significance of their differences was reduced and ultimately
      eliminated after sequential adjustment for diabetes severity, HbA(1c), body mass
      index, regimen adherence, and self-blood-glucose monitoring. Insulin-treated
      patients reported significantly higher distress than oral- or diet-treated
      patients on 16 of 20 PAID items. 'Worrying about the future' and 'guilt/anxiety
      when ... off track with diabetes' were the top two serious problems (PAID >or= 5)
      in all treatment groups. Not accepting diabetes diagnosis was a top concern for
      oral- and diet-treated patients, and unclear management goals distressed diet
      treated patients. CONCLUSIONS: Primary care patients treated with insulin
      reported higher diabetes-related emotional distress compared with oral- or diet
      treated patients. Greater distress was largely explained by greater disease
      severity and self-care burdens. To improve diabetes-specific quality of life,
      clinicians should address patients' sense of worry and guilt, uncertain
      acceptance of diabetes diagnosis, and unclear treatment goals.

PMID- 17227325
TI  - Long-term effects of a structured intensive diabetes education programme (SIDEP)
      in patients with Type 2 diabetes mellitus--a 4-year follow-up study.
AB  - AIMS: Patient education is a very important part of diabetes care. However, until
      now, little data has been presented about the long-term effectiveness of
      structured intensive diabetes education programmes (SIDEP) for people with Type 2
      diabetes mellitus. METHODS: People with Type 2 diabetes (n = 547) hospitalized
      from December 1999 to December 2000 were randomly assigned to two groups. Two
      hundred and nineteen patients undertook an inpatient SIDEP and the remaining
      patients received conventional glycaemic control without intensive education.
      After discharge, all patients were monitored regularly. Laboratory data were
      obtained, and adherence to self-care behaviour was determined on a five-point
      scale by questionnaires completed annually. RESULTS: Of the patients who
      completed the SIDEP, 160 (73.1%) were followed up for more than 4 years. The mean
      HbA(1c) (7.9 +/- 1.2 vs. 8.7 +/- 1.6%; P < 0.05) and the frequency of
      hospitalization related to diabetes per patient per year (0.3 +/- 0.6 vs. 0.8 +/-
      0.9; P < 0.05) was significantly lower in the SIDEP group than in the control
      group. The SIDEP group adhered more closely to self-care behaviour than the
      control group over 4 years (P < 0.05). People with Type 2 diabetes mellitus of
      longer duration and those treated with insulin had poorer HbA(1c) at follow-up.
      CONCLUSIONS: A well-designed, intensive patient education programme is necessary
      for people with diabetes. However, regular and sustained reinforcement with
      encouragement is also required to maintain optimal glycaemic control, especially
      in insulin-treated patients.

PMID- 17227326
TI  - Long-term effects of leisure time physical activity on risk of insulin resistance
      and impaired glucose tolerance, allowing for body weight history, in Danish men.
AB  - AIMS: To determine if the level of leisure time physical activity (LTPA) in young
      adulthood in obese and non-obese men reduces the risk of insulin resistance (IR)
      and impaired glucose tolerance (IGT) in middle age, and if such an effect is
      explained by the current level of LTPA, or by the body mass index (BMI) history
      preceding and subsequent to the assessment of LTPA. METHODS: Longitudinal study
      of groups of obese and randomly selected non-obese men identified at around age
      19, and re-examined at mean ages of 32, 44 and 51. BMI was measured at all four
      examinations. LTPA was assessed by self-administrated questionnaires at the last
      three examinations. IR and the presence of IGT was determined by an oral glucose
      tolerance test at the last examination. RESULTS: LTPA in young adulthood reduced
      the risk of IR and IGT in middle age throughout the range of BMI. Adjustment for
      the BMI history preceding and subsequent to the assessment of LTPA attenuated the
      association with IR and IGT, but active men remained at low risk of IR and IGT.
      Adjustment for subsequent and current levels of LTPA, smoking habits, alcohol
      intake, educational level and family history of diabetes had no notable influence
      on the results. CONCLUSION: LTPA appears to reduce the risk of IR and IGT, an
      effect which is not explained by the current level of physical activity, and only
      partially explained by the BMI history preceding and subsequent to the assessment
      of LTPA.

PMID- 17227327
TI  - How many cases of Type 2 diabetes mellitus are due to being overweight in middle
      age? Evidence from the Midspan prospective cohort studies using mention of
      diabetes mellitus on hospital discharge or death records.
AB  - AIMS: To relate body mass index (BMI) in middle age to development of diabetes
      mellitus. METHODS: Participants were 6927 men and 8227 women from the
      Renfrew/Paisley general population study and 3993 men from the Collaborative
      occupational study. They were aged 45-64 years and did not have reported diabetes
      mellitus. Cases who developed diabetes mellitus, identified from acute hospital
      discharge data and from death certificates in the period from screening in 1970
      1976 to 31 March 2004, were related to BMI at screening. RESULTS: Of
      Renfrew/Paisley study men 5.4%, 4.8% of women and 5% of Collaborative study men
      developed diabetes mellitus. Odds ratios for diabetes mellitus were higher in the
      overweight group (BMI 25 to < 30 kg/m(2)) than in the normal weight group (BMI
      18.5 to < 25 kg/m(2)) and highest in the obese group (BMI >or= 30 kg/m(2)).
      Compared with the normal weight group, age-adjusted odds ratios for overweight
      and obese Renfrew/Paisley men were 2.73 [95% confidence interval (CI) 2.05, 3.64]
      and 7.26 (95% CI 5.26, 10.04), respectively. Further subdividing the normal,
      overweight and obese groups showed increasing odds ratios with increasing BMI,
      even at the higher normal level. Assuming a causal relation, around 60% of cases
      of diabetes could have been prevented if everyone had been of normal weight.
      CONCLUSIONS: Overweight and obesity account for a major proportion of diabetes
      mellitus, as identified from hospital discharge and death records. With recent
      increases in the prevalence of overweight, the burden of disease related to
      diabetes mellitus is likely to increase markedly. Primordial prevention of
      obesity would be a major strategy for reducing the incidence of diabetes mellitus
      in populations.

PMID- 17227328
TI  - Asymmetrical dimethylarginine is related to renal function, chronic inflammation
      and macroangiopathy in patients with Type 2 diabetes and albuminuria.
AB  - AIMS: Patients with Type 2 diabetes mellitus (T2DM) and micro- and
      macroalbuminuria are at increased cardiovascular risk. The endogenous nitric
      oxide synthase inhibitor asymmetrical dimethylarginine (ADMA) is increased in
      renal failure and could promote atherosclerosis. To determine the relationship
      between ADMA, renal albumin excretion rate (AER) and cardiovascular risk, we
      studied 103 T2DM patients. METHODS: ADMA, symmetrical dimethylarginine (SDMA) and
      L-arginine were determined by high-performance liquid chromatography in plasma
      from 36 normo-, 40 micro- and 27 macroalbuminuric patients with T2DM (age 64 +/-
      11 years; 38 women) who had comparable age, sex and metabolic parameters. Forty
      six patients had macrovascular disease (MVD). RESULTS: ADMA was significantly
      increased in patients with micro- and macroalbuminuria [median 0.61
      (interquartile range 0.55-0.70) micromol/l and 0.62 (0.50-0.79) micromol/l,
      respectively] compared with those with normoalbuminuria [0.55 (0.48-0.63)
      micromol/l; both P < 0.05]. SDMA was elevated in micro- and macroalbuminuria
      [0.57 (0.42-0.80) micromol/l and 0.64 (0.50-0.96) micromol/l] compared with
      normoalbuminuric subjects [0.44 (0.37-0.53) micromol/l; both P < 0.01]. Patients
      with increased AER and MVD had higher ADMA and SDMA compared with those without
      MVD (both P < 0.001). L-arginine was comparable between all groups. ADMA
      correlated significantly with high-sensitivity C-reactive protein (hsCRP) and
      glomerular filtration rate (GFR) but not with the extent of albumin excretion,
      body mass index, fasting glucose, HbA(1c) or plasma lipids. CONCLUSIONS:
      Increased ADMA in T2DM patients with albuminuria is linked to cardiovascular
      disease and is associated with renal dysfunction and subclinical inflammation.

PMID- 17227329
TI  - Experiences of patients with insulin-treated diabetes in conscript military
      service.
AB  - AIMS: To determine how young adults with insulin therapy manage daily care of
      diabetes during the physically demanding conditions of conscript military
      service, and to evaluate the effects of military service on glycaemic control and
      on the incidence of acute diabetic complications. METHODS: An observational study
      of 47 young male volunteer conscripts receiving insulin therapy was carried out
      at the Signal Regiment in Riihimaki from January 2001 to July 2005. Outcome
      measures were drop-out rate from service, management of diabetes care, glycaemic
      control, and occurrence of severe hypoglycaemia or ketoacidosis during service.
      RESULTS: Forty (85%) diabetic conscripts completed service, with service time
      ranging from 180 to 362 days, and seven (15%) interrupted service. One-third of
      conscripts reported difficulties during military training with insulin injections
      and blood glucose testing. The mean HbA(1c) during service increased by 0.6%
      units (P = 0.007) from baseline. Five events of severe hypoglycaemia in three
      conscripts (overall incidence rate 0.15 per patient-year) and one ketoacidosis
      event occurred. Diabetic conscripts were chosen for leadership training more
      often than non-diabetic conscripts. CONCLUSIONS: Our data suggest that selected
      and motivated adolescents on insulin therapy can manage the daily care of
      diabetes and maintain appropriate glycaemic control during service, although the
      risk of severe hypoglycaemia exists.

PMID- 17227330
TI  - Bone loss in diabetic patients with chronic kidney disease.
AB  - OBJECTIVE: We investigated whether loss of bone is detectable during follow-up of
      diabetic patients with chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS:
      In 40 initially non-dialysed diabetic patients with CKD (isotopic glomerular
      filtration rate < 60 ml/min/1.73 m(2) or albumin excretion rate > 30 mg/24 h),
      body composition (DEXA scan) and glomerular filtration rate (GFR determined from
      (51)Cr-EDTA clearance) were measured at a 2-year interval, and compared by paired
      t-tests. RESULTS: The 40 patients, mainly with Type 2 diabetes (n = 28), were men
      (n = 28), aged 65 +/- 11 years, with diabetes duration 18 +/- 11 years. GFR was
      initially 38.0 (range 8-89) ml/min/1.73 m(2). CKD progressed during follow-up:
      eight started haemodialysis and GFR declined in the 32 others (P < 0.05 vs.
      initial). T-scores for total body (initial -0.61 +/- 1.11, final -1.11 +/- 1.40;
      P < 0.001) and femoral neck (initial -1.88 +/- 0.15, final -2.07 +/- 0.15; P <
      0.05) declined. Ten patients were osteopaenic at baseline (no osteoporosis),
      whereas most were osteopaenic (n = 21, P < 0.05) and five were osteoporotic at
      final assessment. The 16 patients who became osteopaenic or osteoporotic during
      follow-up did not differ from the others for the type of diabetes, age, GFR,
      albumin excretion rate, HbA(1c), GFR reduction and the requirement for dialysis
      during follow-up. They were all men (P < 0.01 by chi-squared test), with reduced
      initial total body T-score (-1.20 +/- 0.82, others -0.32 +/- 1.13; P < 0.05) and
      a lower body mass index (24.6 +/- 4.3; others 27.7 +/- 4.3; P < 0.05).
      CONCLUSION: Bone loss, especially in the femoral neck, is progressive in diabetic
      patients with CKD.

PMID- 17227332
TI  - Transient and persistent impaired glucose tolerance and progression to diabetes
      in South Asians and Europeans: new, large studies are a priority.

PMID- 17227331
TI  - Paradoxical HDL-C reduction during rosiglitazone and fibrate treatment.
AB  - AIMS: Dyslipidaemia in Type 2 diabetes mellitus (T2DM) is one of the major
      contributors in the pathogenesis of atherosclerosis. Thiazolidinediones (TZD), a
      class of drugs used in the treatment of T2DM, also modify lipids, especially
      lowering serum triglycerides and raising high-density lipoprotein cholesterol
      (HDL-C). METHODS: We describe five patients taking rosiglitazone and a fibrate
      who showed a paradoxical fall in HDL-C, which would have been missed if HDL-C had
      not been routinely monitored. This could have had a major impact in increasing
      the cardiovascular risk in these patients. RESULTS: Our five patients showed
      marked variation in both the decrease in serum HDL-C (50-89%) and also in the
      time taken for recovery of HDL-C after withdrawal of rosiglitazone (between 5 and
      20 weeks). Apolipoprotein A1 mirrored the drop in HDL-C in four of the five
      patients but in one subject this was not seen, suggesting the possibility of
      multiple mechanisms leading to the phenomenon described, perhaps involving HDL
      metabolism. Improvements in glycaemic control with rosiglitazone (absolute
      HbA(1c) reduction between 0.6 and 3.0%) were seen in four of our patients. This
      suggests that the peroxisomal proliferator-activated receptor gamma signalling
      pathways relevant to glucose homeostasis were intact. CONCLUSION: As
      atherosclerosis is associated with a decrease in the HDL-C level, our
      observations reinforce the message that HDL-C should be measured before and after
      the commencement of rosiglitazone and also on increasing the dosage

PMID- 17227333
TI  - No association between CD14 (C-260-->T) variant and plasma triglycerides or body
      mass index in non-diabetic Caucasians.

PMID- 17227335
TI  - Effect of a pocket-size tablet-dispensing device on glycaemic control in Type 2
      diabetic patients.

PMID- 17227338
TI  - Ergotamine use in severe diabetic autonomic neuropathy.

PMID- 17227340
TI  - Signaling networks that regulate muscle development: lessons from zebrafish.
AB  - Locomotion mediated by skeletal muscle provides a basis for the behavioral
      repertoire of most animals. Embryological and genetic studies of mouse, bird,
      fish and frog embryos are providing insights into the functions of the myogenic
      regulatory factors (MRFs) and the signaling molecules that regulate activity of
      MRFs. Nevertheless, our understanding of muscle development remains somewhat
      limited. Fundamental goals are to elucidate how mesodermal cells are induced
      during gastrulation to form muscle precursor cells and how muscle precursor cells
      acquire specific cell fates, such as slow and fast muscle cells. In this review,
      we focus on studies of zebrafish muscle development that have advanced our
      understanding of the molecular genetics of muscle cell induction and
      specification.

PMID- 17227341
TI  - Dan is required for normal morphogenesis and patterning in the developing chick
      inner ear.
AB  - During vertebrate inner ear development, compartmentalization of the auditory and
      vestibular apparatuses along two axes depends on the patterning of transcription
      factors expressed in a region-specific manner. Although most of the patterning is
      regulated by extrinsic signals, it is not known how Nkx5.1 and Msx1 are
      patterned. We focus on Dan, the founding member of the Cerberus/Dan gene family
      that encodes BMP antagonists, and describe its function in morphogenesis and
      patterning. First, we confirmed that Dan is expressed in the dorso-medial region
      of the otic vesicle that corresponds to the presumptive endolymphatic duct and
      sac (ed/es). Second, we used siRNA knockdown to demonstrate that depletion of Dan
      induced both a severe reduction in the size of the ed/es and moderate deformities
      of the semicircular canals and cochlear duct. Depletion of Dan also caused
      suppression of Nkx5.1 in the dorso-lateral region, suppression of Msx1 in the
      dorso-medial region, and ectopic induction of Nkx5.1 and Msx1 in the ventro
      medial region. Most of these phenotypes also appeared following misexpression of
      the constitutively active form of BMP receptor type Ib. Thus, Dan is required for
      the normal morphogenesis of the inner ear and, by inhibiting BMP signaling, for
      the patterning of the transcription factors Nkx5.1 and Msx1.

PMID- 17227342
TI  - Microarray analysis of zygotic expression of transcription factor genes and cell
      signaling molecule genes in early Ciona intestinalis embryos.
AB  - In ascidians, specification of embryonic cells takes place very early at the 16-,
      32- and 64-cell stages, and this developmental event involves zygotic expression
      of various genes, some encoding transcription factors and some encoding cell
      signaling molecules. Previous studies have demonstrated that approximately 50
      transcription factor genes and 25 signaling molecule genes commence their zygotic
      expression by the 64-cell stage of Ciona intestinalis embryos. With the aid of
      oligonucleotide-based microarray, we examined the zygotic expression profiles of
      developmental genes in early Ciona embryos. Although the microarray method had a
      tendency to barely detect zygotic expression of genes that are expressed
      maternally, the present results confirmed the results of previous studies. In
      addition, the present analysis demonstrated the zygotic expression of four genes
      that were not identified in previous studies, and this result was confirmed by
      whole-mount in situ hybridization. Our results therefore provide further
      information on the developmental genes that are zygotically expressed in early
      Ciona embryos, and demonstrate that the microarray is a powerful tool for future
      studies of the gene regulatory network in Ciona, a basal chordate with a body
      plan similar to that of vertebrates.

PMID- 17227343
TI  - Characterization of the sperm-associated body and its role in the fertilization
      of the chicken Gallus domesticus.
AB  - The present paper aimed to characterize the substance forming the sperm
      associated body (SB), to find its producing sites, and to show its functions in
      the fertilization of chicken. The SB was found both in between the inner and
      outer layers of vitelline membranes around eggs and in the oviductal
      infundibulum. Material from which the SB is constructed (SB substance) was
      isolated from the vitelline membranes. It was a hydrophobic protein with a
      molecular size of 570 kDa. X-ray microanalysis detected calcium in the aggregates
      of the SB substance. Immunofluorescence and immunoelectron microscopy showed that
      the substance was produced in secretory cells in the luminal epithelium of the
      oviductal infundibulum and was provided to the egg on and in its vitelline
      membrane. During incubation, the SB substance bound with spermatozoa in the
      posterior portion of their flagella. Holes and disks were found in the vitelline
      membranes of fertile eggs at a ratio of 1: 19-24. Over 94% of the holes were
      accompanied by SB. The presence of SB is necessary for fertile spermatozoa to
      make holes in the membrane and to enter the fertile egg.

PMID- 17227344
TI  - Improved method for visualizing cells revealed dynamic morphological changes of
      ventral neuroblasts during ventral cleft closure of Caenorhabditis elegans.
AB  - The formation of intricate and functional biological structures depends on the
      dynamic changes of cellular morphology. Confocal laser scanning microscopy (CLSM)
      is a widely used method to reveal the three-dimensional (3-D) structure of cells
      during the development of Caenorhabditis elegans (C. elegans) and other model
      organisms. Improving the efficiency and image quality of CLSM would benefit
      studies using this method. We found that CED-10::GFP::CED-10, a green fluorescent
      protein (GFP) marker, is intensely expressed beneath the cell surface,
      facilitating visualization of cellular morphology in C. elegans embryos. By
      combining the unique properties of this marker, and with the help of direct 3-D
      rendering of images obtained by CLSM, we developed a simple but powerful method
      for investigating cellular morphology in developing embryos. Using this method
      we, for the first time, document the dynamic changes in the morphology of ventral
      neuroblasts in vivo during ventral cleft closure.

PMID- 17227345
TI  - Biochemical composition of ovine follicular fluid in relation to follicle size.
AB  - The aim of this study was to biochemically characterize ovine follicular fluid
      and to relate possible changes in composition to follicular size. Ovaries were
      collected from adult and cycling non-pregnant slaughtered sheep (Ovis aries)
      during breeding season. A total of 104 pairs of ovaries were investigated and
      these data were then compared. Follicular fluid was aspirated from small (< 2
      mm), medium (2-4 mm) and large (> 4 mm) nonatretic ovarian follicles. The
      follicular fluid was centrifuged at 4 degrees C and 5000 g for 30 min to remove
      any cells and stored at -80 degrees C prior to assay. Follicular fluid samples
      were analyzed for glucose, total protein, cholesterol, triglycerides, lactate,
      urea, creatinine, sodium, potassium, chloride, calcium, phosphorus, magnesium,
      acid phosphatase, alkaline phosphatase, and lactate dehydrogenase. Data were
      analyzed by the linear regression model. As follicles became larger, the
      concentrations of glucose and cholesterol significantly (P < 0.05) increased
      while those of triglycerides, lactate, alkaline phosphatase and lactate
      dehydrogenase significantly (P < 0.05) decreased.

PMID- 17227346
TI  - Quantitation of the male and female types of mitochondrial DNA in a blue mussel,
      Mytilus galloprovincialis, using real-time polymerase chain reaction assay.
AB  - The system termed doubly uniparental inheritance (DUI) of mitochondrial
      transmission to progeny has been reported in Mytilus. Under DUI, it has been
      thought that males have both paternally (M type) and maternally (F type)
      transmitted mitochondrial DNA (mtDNA), and females have only F type. However, the
      presence of M type in females has been reported. To clarify the ratio of M type
      to F type mtDNA in female and male tissues to further our understanding of
      mitochondrial transmission, we developed a procedure to measure the copy numbers
      of the two types of mtDNA in Mytilus galloprovincialis using a real-time
      polymerase chain reaction assay. The following results were obtained by this
      method. In females, the copy numbers of M type mtDNA detected in adductor muscle,
      gonad and eggs were approximately 10 000-fold lower than those of F type. In
      males, F type dominated in adductor muscle, as in the female tissue. However,
      copy numbers of M type mtDNA were approximately 1000-fold higher than those of F
      type in gonad and 100 000-fold higher than those of F type in sperm. We examined
      the quantity relationship between the two types of mtDNA and the transmission
      mechanism of mtDNA in M. galloprovincialis.

PMID- 17227347
TI  - Therapeutic patient education in oncology: pedagogical notions for women's health
      and prevention.
AB  - Therapeutic patient education has been defined by the World Health Organization
      as a comprehensive approach to support patients and their families to better
      understanding of their diseases. In oncology, the contribution of therapeutic
      education may enable the patients to have adequate information of the illness, to
      actively participate in the management of the disease, to understand how to live
      with the illness, to learn how to face the critical moments of the clinical
      course, and to live in harmony with all health professionals. In addition, there
      may be several advantages for health professionals: a reduction in emotional
      labour, increased professional satisfaction, and a reduction in the potential
      tensions and conflicts with patients and their relatives. We suggest that
      therapeutic patient education in oncology may be useful for both patients and
      health professionals and probably lead to a reduction in the costs of healthcare
      delivery.

PMID- 17227348
TI  - Microbiology and management of infected solid tumours.
AB  - Infection has been recognized as one of the major obstacles to the successful
      management of patients with malignant tumours. Aerobic and anaerobic bacteria of
      endogenous source are a major cause of infections in the necrotic tumour,
      especially when they occur in proximity to a site where these bacteria reside as
      part of the normal flora. Although surgical removal or evacuation of the purulent
      fluid is preferred, this is not always feasible in a patient with a malignant
      tumour. Antimicrobial therapy against potential bacterial pathogens is often the
      sole therapy or is used along with surgical drainage or removal of the infected
      area. This review describes the microbiology and management of infection in
      necrotic tumours.

PMID- 17227349
TI  - Returning to work following cancer: a qualitative exploratory study into the
      experience of returning to work following cancer.
AB  - The experience of returning to work following cancer is a largely unknown area of
      cancer research. This preliminary study aimed to explore the factors that
      influence decisions about return to work either during or after cancer treatment
      and to identify the important aspects of returning to work. Qualitative data were
      collected using individual interviews (n = 19) and two focus groups (n = 4, n =
      6), predominantly with breast cancer survivors. Patterns of returning to work
      were diverse and a variety of reasons influenced work decisions, including
      financial concerns and regaining normality. Participants also discussed their
      ability to work, health professionals' advice, side effects, support and
      adjustments, and attitudes towards work. Although the majority adapted well, a
      few encountered difficulties on their return. It is evident that more advice is
      required from health professionals about returning to work, along with reasonable
      support and adjustments from employers to ensure that cancer survivors are able
      to successfully reintegrate back into the workforce.

PMID- 17227351
TI  - Cancer Information and Support Centres: fixing parts cancer drugs cannot reach.

PMID- 17227350
TI  - Factors causing early relapse after lung metastasis surgery.
AB  - Haematogenous lung metastases are usually considered a sign of widespread
      metastatic disease. However, in most primary cancers, the first filter for
      distant tumours are the lungs. In some patients, the metastatic process may stop
      at the lungs. In these selected patients, there are studies that have shown the
      benefits of metastasectomy. The objective of this paper is to analyse the
      morbidity and mortality of lung metastasectomy and determine the factors that
      predispose to early relapse. Forty-two patients operated on for lung metastases,
      and four were excluded as they were assessed intraoperatively to be unresectable,
      leaving 38 patients to be analysed. The variables analysed were: age, sex,
      primary tumour, disease-free interval, number of metastases, bilaterality,
      morbidity and mortality, relapse, reinterventions, relapse-free interval after
      metastasectomy and survival. The surgical technique was a posterolateral
      thoracotomy, and there were no perioperative deaths. Morbidity was 11% (n = 4),
      and surgical reintervention of the haemothorax was necessary. Survival after 1, 2
      or 3 years was 87%, 61% and 25% respectively, and the percentage of relapse-free
      patients was 71%, 56% and 17% respectively. The main factors associated with
      early relapse were histological type of tumour (more relapse in sarcoma, and less
      in adenocarcinoma), the disease-free interval between the primary tumour and lung
      metastases, and the number of metastases. Surgery was required a second time in
      five patients who had relapsed lung metastases, but extirpation could be
      performed in only four patients, of whom three were relapse free after 6, 12 and
      24 months respectively, and the fourth had relapsed lung metastases after 18
      months. Resection of lung metastases can be performed with low morbidity and
      mortality. The main prognostic factors for survival are complete surgery,
      histological type, disease-free interval between the primary tumour and
      metastases, and the number of lung metastases.

PMID- 17227352
TI  - The social and emotional toll of chemotherapy - patients' perspectives.
AB  - The aim of this paper is to briefly describe the unique methodology employed by
      nine nurse researchers who conducted research into the social and emotional
      effects of chemotherapy from the patient's perspective, and to present four
      dominant themes. The research developed from discussions at a local UK Nurses
      Oncology Forum, during which nurses voiced their concern about the social and
      emotional implications for people receiving chemotherapy. It was anticipated that
      understanding the issues from the patient's perspective would assist nurses to
      reconsider and reshape the care provided, particularly in the chemotherapy
      clinic. Using principles of phenomenology, the nurse researchers collected data
      from participants using conversational-style interviews. Some participants kept
      diaries of chemotherapy experiences. These data were subsequently analysed using
      a modified phenomenological analysis framework. Nineteen people were recruited to
      the study, resulting in 98 interviews and seven diaries. Eight major themes
      emerged from the data: striving for normality, the role of significant others,
      feeling up - feeling down, flagging, being sociable, anxiety, the chemotherapy
      process, and participating in the research. Relationship dynamics, the perceived
      role of significant others and the frustrations associated with lack of
      concentration and memory loss are important findings that should influence
      nursing care and management.

PMID- 17227353
TI  - Evaluating partnership working: lessons for palliative care.
AB  - Partnership working in palliative care is being increasingly promoted as the
      solution to poorly coordinated health and social care services. A key example is
      the UK National Institute for Clinical Excellence (NICE) guidance on supportive
      and palliative care. However, partnerships have costs in negotiating, developing
      and maintaining working relationships and translating these into successful
      outcomes, so may not always be the best or most effective method of service
      improvement. This article explores structural, procedural, financial,
      professional and legitimacy barriers to partnership working. We conclude that
      these five barriers could be sufficient to destroy emerging partnerships. Nowhere
      in the NICE guidance on supportive and palliative care are such barriers
      acknowledged. We suggest that current and projected palliative care partnerships
      should be critically evaluated against both process and outcome success criteria.
      Such evaluations must be integral to partnerships, to learn about what makes an
      effective palliative care partnership, and what affects partnerships have on
      patient care and outcomes. Partnerships may not be the panacea for issues of
      fragmentation, and should not be the only solution considered. Lessons should be
      learnt from the UK's promulgation of partnerships to ensure that these are used
      appropriately and only where patient benefit can be anticipated.

PMID- 17227354
TI  - Exercise stage of change, barriers, expectations, values and preferences among
      breast cancer patients during treatment: a pilot study.
AB  - With increasing evidence supporting physical activity benefits during breast
      cancer treatment, addressing exercise adherence with consideration of the unique
      exercise barriers, outcome expectations and preferences of cancer patients is
      needed. Our pilot study aimed to determine the following during breast cancer
      treatment: (1) exercise barriers, outcome expectations/values and associations
      with exercise stage of change and (2) exercise preferences. A cross-sectional
      survey was administered to 23 breast cancer patients during treatment.
      Participants were primarily aged 50-60 years (52%), Caucasian (91%), with stage I
      (30%), II (44%) or III (26%) disease. A total of 48% were receiving chemotherapy.
      In total, 50% were in the pre-contemplation/contemplation stage of change, with
      34% in action/maintenance. Common exercise adherence barriers (i.e. lack of
      priority, self-discipline, procrastination and fatigue) demonstrated
      statistically significant negative associations with exercise. Frequent outcome
      expectations included improving heart/lungs, reducing disease risk, building
      muscle strength and losing weight. Important outcomes included improving state of
      mind, reducing fatigue and avoiding injury. Outcome expectations (i.e. less
      depression, boredom and nausea) were positively associated with exercise. The
      majority preferred walking (100%), moderate-intensity (61%), home-based (78%)
      exercise. Among breast cancer patients during treatment, exercise adherence
      barriers are general and disease specific. Outcome expectations are physical
      benefits, with the most important outcomes being psychological or avoidance of
      risk (i.e. injury).

PMID- 17227356
TI  - Patients' subjective symptoms, quality of life and intake of food during the
      recovery period 3 and 12 months after upper gastrointestinal surgery.
AB  - Few studies describe patients' quality of life and their experienced symptoms
      during the recovery period after having undergone upper gastrointestinal surgery
      at 3 and 12 months. The aims of this study were to explore patients' quality of
      life and symptoms preoperatively and at 3 and 12 months following upper
      gastrointestinal surgery and to describe and compare patients' experiences of
      appetite, food intake, weight changes, tiredness and sleeping patterns. A
      descriptive and comparative quantitative design was used. Three instruments were
      used: the Gastrointestinal Symptom Rating Scale, the European Organisation for
      Research and Treatment of Cancer Quality of Life Questionnaire and the Eating
      Dysfunction Scale. A questionnaire was used to investigate symptoms such as mood,
      appetite, sleep, activities and well-being. Twenty-four patients were included in
      the study. The major results were that anxiety levels and global health status
      decreased and that patients felt more disappointed after 12 months compared with
      after 3 months. Four patients at 3 months after surgery and eight patients at 12
      months regained their weight compared with the situation before surgery. The
      contribution of nursing care activities focusing on the importance of food intake
      and the patients' current and historical medical records in relation to their
      health status should continue to be examined and researched over a longer period
      of time.

PMID- 17227355
TI  - Safety and efficacy of transdermal fentanyl in patients with cancer pain: phase
      IV, Turkish oncology group trial.
AB  - We have performed a prospective evaluation of the efficacy, safety and
      convenience of the transdermal therapeutic system - fentanyl (TTS-F) in Turkish
      cancer patients when it was newly available in Turkey. Ninety-nine patients with
      historically confirmed malignancy and pain entered the study; the mean age was
      55.1 (16-58) years. The study duration was 28 days. Transdermal therapeutic
      system - fentanyl was used in opioid-naive or pre-treated patients. Most patients
      reported a decrease in pain severity. Use of rescue medication decreased from day
      4 to day 28. The majority of patients rated patch convenience of use as
      excellent. A total of 22.2% of patients experienced adverse events that were
      either probably related or very likely to be related to the study drug. The
      majority of the adverse events mentioned were related to the digestive system.
      Eighteen serious adverse events were reported by 13 patients. Six events were
      doubtfully related, and 12 events were not related to the study drug. Four
      patients died during the trial. None of these deaths was attributed to the study
      drug. In conclusion, the trial showed that TTS-F is easily managed, effective and
      will help to enable the appropriate opioid administration to patients who are
      suffering from cancer pain in Turkey.

PMID- 17227357
TI  - Tumour marker prescriptions for cancer screening in the Hellenic primary care.
AB  - Tumour markers are neither sensitive nor specific enough for cancer screening.
      Despite established guidelines, tumour marker 'screening myth' may be alive among
      physicians, but no study has analysed the phenomenon. This study aims to
      investigate tumour marker recommendation for screening purposes in primary care
      setting. A total of 209 Hellenic physicians were surveyed for screening
      activities by a multiple-choice questionnaire. Data were abstracted for the
      following tumour marker recommendations: carcinoembryonic antigen (CEA); cancer
      antigens 19.9, 125 and 15.3; alpha-fetoprotein and beta-human chorionic
      gonadotropin (beta-HCG). A high rate of physicians advocate that tumour markers
      in cancer screening (range from 24% for beta-HCG to 46% for CEA). This phenomenon
      is not related to age, sex, type and level of physicians' specialization. In
      conclusion, many physicians recommend tumour markers for screening purposes. This
      may be harmful, since their prescriptions unnecessarily burden health economics,
      and further evaluation of false-positive findings might be associated with
      increased costs and risk from additional diagnostic/therapeutic interventions.

PMID- 17227358
TI  - Using e-learning as a tool for multidisciplinary education.

PMID- 17227362
TI  - Cryptic variation in butterfly eyespot development: the importance of sample size
      in gene expression studies.
AB  - Previous studies have shown that development can be robust to variation in
      parameters such as the timing or level of gene expression. This leads to the
      prediction that natural populations should be able to host developmental
      variation that has little phenotypic effect. Cryptic variation is of particular
      interest because it can result in selectable phenotypes when "released" by
      environmental or genetic factors. Currently, however, we have little idea of how
      variation is distributed between genes or over time in pattern formation
      processes. Here we survey expression of Notch (N), Spalt (Sal), and Engrailed
      (En) during butterfly eyespot determination to better understand how pattern
      formation may vary within a population. We observed substantial heterochronic
      variance in the progress of spatial expression patterns for all three proteins,
      suggesting some degree of developmental buffering in eyespot development. Peak
      variance for different proteins was found at both early and late stages of
      development, contrasting with previous models suggesting that the distribution of
      variance should be more temporally focused during pattern formation. We speculate
      that our observations are representative of a standing reservoir of cryptic
      variation that may contribute to phenotypic evolution under certain
      circumstances. Our results also provide a strong cautionary message that gene
      expression studies with limited sample sizes can be positively misleading in
      terms of inferring expression pattern time series, as well as for making cross
      species phylogenetic comparisons.

PMID- 17227363
TI  - Molecular paleoecology: using gene regulatory analysis to address the origins of
      complex life cycles in the late Precambrian.
AB  - Molecular paleoecology is the application of molecular data to test hypotheses
      made by paleoecological scenarios. Here, we use gene regulatory analysis to test
      between two competing paleoecological scenarios put forth to explain the
      evolution of complex life cycles. The first posits that early bilaterians were
      holobenthic, and the evolution of macrophagous grazing drove the exploitation of
      the pelagos by metazoan eggs and embryos, and eventually larvae. The alternative
      hypothesis predicts that early bilaterians were holopelagic, and new adult stages
      were added on when these holopelagic forms began to feed on the benthos. The
      former hypothesis predicts that the larvae of protostomes and deuterostomes are
      not homologous, with the implication that larval-specific structures, including
      the apical organ, are the products of convergent evolution, whereas the latter
      hypothesis predicts homology of larvae, specifically homology of the apical
      organ. We show that in the sea urchin, Strongylocentrotus purpuratus, the
      transcription factors NK2.1 and HNF6 are necessary for the correct spatial
      expression profiles of five different cilia genes. All of these genes are
      expressed exclusively in the apical plate after the mesenchyme-blastula stage in
      cells that also express NK2.1 and HNF6. In addition, abrogation of SpNK2.1
      results in embryos that lack the apical tuft. However, in the red abalone,
      Haliotis rufescens, NK2.1 and HNF6 are not expressed in any cells that also
      express these same five cilia genes. Nonetheless, like the sea urchin, the
      gastropod expresses both NK2.1 and FoxA around the stomodeum and foregut, and
      FoxA around the proctodeum. As we detected no similarity in the development of
      the apical tuft between the sea urchin and the abalone, these molecular data are
      consistent with the hypothesis that the evolution of mobile, macrophagous
      metazoans drove the evolution of complex life cycles multiple times independently
      in the late Precambrian.

PMID- 17227364
TI  - Expression of Pax gene family members in the anthozoan cnidarian, Nematostella
      vectensis.
AB  - Pax genes are a family of homeodomain transcription factors that have been
      isolated from protostomes (e.g., eight in Drosophilia) and deuterostomes (e.g.,
      nine in vertebrates) as well as outside the Bilateria, from sponges, a placozoan,
      and several classes of cnidarians. The genome of an anthozoan cnidarian, the
      starlet sea anemone, Nematostella vectensis, has been surveyed by both degenerate
      polymerase chain reaction and in silico for the presence of Pax genes. N.
      vectensis possesses seven Pax genes, which are orthologous to cnidarian Pax genes
      (A,B,C, and D) previously identified in another anthozoan, a coral, Acropora
      millepora. Phylogenetic analyses including data from nonchordate deuterostomes
      indicates that there were five Pax gene classes in the protostome-deuterostome
      ancestor, but only three in the cnidarian-bilaterian ancestor, with PaxD class
      genes lost in medusozoan cnidarians. Pax genes play diverse roles in bilaterians,
      including eye formation (e.g., Pax6), segmentation (e.g., Pax3/7 class genes),
      and neural patterning (e.g., Pox-neuro, Pax2/5/8). We show the first expression
      data for members of all four Pax classes in a single species of cnidarian. N.
      vectensis Pax genes are expressed in both a cell-type and region-specific manner
      during embryogenesis, and likely play a role in patterning specific components of
      the cnidarian ectodermal nerve net. The results of these patterns are discussed
      with respect to Pax gene evolution in the Bilateria.

PMID- 17227365
TI  - Ectoderm- and endomesoderm-specific GATA transcription factors in the marine
      annelid Platynereis dumerilli.
AB  - The GATA family of transcription factors appears to retain conserved roles in
      early germ layer patterning in most, if not all, animals; however, the number and
      structure of GATA factor genes varies substantially when different animal genomes
      are compared. Thus, the origin and relationships of invertebrate and vertebrate
      GATA factors, and their involvement in animal germ layer evolution, are unclear.
      We identified two highly conserved GATA factor genes in a marine annelid, the
      polychaete Platynereis dumerilii. A phylogenetic analysis indicates that the two
      Platynereis GATA factors are orthologous to the GATA1/2/3 and GATA4/5/6
      subfamilies present in vertebrates. We also identified conserved motifs within
      each GATA class, and assigned the divergent Caenorhabditiselegans and Drosophila
      melanogaster GATA factor genes to the vertebrate classes. Similar to their
      vertebrate homologs, PdGATA123 mRNA expression was restricted to ectoderm,
      whereas PdGATA456 was detected only in endomesoderm. Finally, we identified in
      genome databases one GATA factor gene in each of two distantly related cnidarians
      that include motifs from both bilaterian GATA factor classes. Our results show
      that distinct orthologs of the two vertebrate GATA factor classes exist in a
      protostome invertebrate, suggesting that bilaterian GATA factors originated from
      GATA1/2/3 and 4/5/6 ancestral orthologs. Moreover, our results indicate that the
      GATA gene duplication and the functional divergence that led to these two
      ancestral GATA factor genes occurred after the split of the bilaterian stem group
      from the cnidarians.

PMID- 17227366
TI  - Gene expression patterns in a novel animal appendage: the sea urchin pluteus arm.
AB  - The larval arms of echinoid plutei are used for locomotion and feeding. They are
      composed of internal calcite skeletal rods covered by an ectoderm layer bearing a
      ciliary band. Skeletogenesis includes an autonomous molecular differentiation
      program in primary mesenchyme cells (PMCs), initiated when PMCs leave the vegetal
      plate for the blastocoel, and a patterning of the differentiated skeletal units
      that requires molecular cues from the overlaying ectoderm. The arms represent a
      larval feature that arose in the echinoid lineage during the Paleozoic and offers
      a subject for the study of gene co-option in the evolution of novel larval
      features. We isolated new molecular markers in two closely related but
      differently developing species, Heliocidaris tuberculata and Heliocidaris
      erythrogramma. We report the expression of a larval arm-associated ectoderm gene
      tetraspanin, as well as two new PMC markers, advillin and carbonic anhydrase.
      Tetraspanin localizes to the animal half of blastula stage H. tuberculata and
      then undergoes a restriction into the putative oral ectoderm and future location
      of the postoral arms, where it continues to be expressed at the leading edge of
      both the postoral and anterolateral arms. In H. erythrogramma, its expression
      initiates in the animal half of blastulae and expands over the entire ectoderm
      from gastrulation onward. Advillin and carbonic anhydrase are upregulated in the
      PMCs postgastrulation and localized to the leading edge of the growing larval
      arms of H. tuberculata but do not exhibit coordinated expression in H.
      erythrogramma larvae. The tight spatiotemporal regulation of these genes in H.
      tuberculata along with other ontogenetic and phylogenetic evidence suggest that
      pluteus arms are novel larval organs, distinguishable from the processes of
      skeletogenesis per se. The dissociation of expression control in H. erythrogramma
      suggest that coordinate gene expression in H. tuberculata evolved as part of the
      evolution of pluteus arms, and is not required for larval or adult development.

PMID- 17227367
TI  - Limb ossification in the Paleozoic branchiosaurid Apateon (Temnospondyli) and the
      early evolution of preaxial dominance in tetrapod limb development.
AB  - Despite the wide range of shapes and sizes that accompany a vast variety of
      functions, the development of tetrapod limbs follows a conservative pattern of de
      novo condensation, branching, and segmentation. Development of the zeugopodium
      and digital arch typically occurs in a posterior to anterior sequence, referred
      to as postaxial dominance, with a digital sequence of 4-3-5-2-1. The only
      exception to this pattern in all of living Tetrapoda can be found in salamanders,
      which display a preaxial dominance in limb development, a de novo condensation of
      a basale commune (distal carpal/tarsal 1+2) and a precoccial development of
      digits I and II. These divergent patterns have puzzled researchers for over a
      century leading to various explanatory hypotheses. Despite many advances in
      research on tetrapod limb development, the divergent evolution of these two
      pathways and its causes are still not understood. Based on an extensive
      ontogenetic series we investigated the pattern of limb development of the 300 Ma
      old branchiosaurid amphibian Apateon. This revealed a preaxial dominance in limb
      development that was previously believed to be unique and derived for modern
      salamanders. The Branchiosauridae are favored as close relatives of extant
      salamanders in most phylogenetic hypotheses of the highly controversial origins
      and relationships of extant amphibians. The findings provide new insights into
      the evolution of developmental pathways in tetrapod limb development, the
      relationships of modern amphibians with possible Paleozoic antecedents, and their
      initial timing of divergence.

PMID- 17227368
TI  - Epigenetic interactions and the structure of phenotypic variation in the cranium.
AB  - Understanding the developmental and genetic basis for evolutionarily significant
      morphological variation in complex phenotypes such as the mammalian skull is a
      challenge because of the sheer complexity of the factors involved. We hypothesize
      that even in this complex system, the expression of phenotypic variation is
      structured by the interaction of a few key developmental processes. To test this
      hypothesis, we created a highly variable sample of crania using four mouse
      mutants and their wild-type controls from similar genetic backgrounds with
      developmental perturbations to particular cranial regions. Using geometric
      morphometric methods we compared patterns of size, shape, and integration in the
      sample within and between the basicranium, neurocranium, and face. The results
      highlight regular and predictable patterns of covariation among regions of the
      skull that presumably reflect the epigenetic influences of the genetic
      perturbations in the sample. Covariation between relative widths of adjoining
      regions is the most dominant factor, but there are other significant axes of
      covariation such as the relationship between neurocranial size and basicranial
      flexion. Although there are other sources of variation related to developmental
      perturbations not analyzed in this study, the patterns of covariation created by
      the epigenetic interactions evident in this sample may underlie larger scale
      evolutionary patterns in mammalian craniofacial form.

PMID- 17227369
TI  - Two AGAMOUS-like MADS-box genes from Taihangia rupestris (Rosaceae) reveal
      independent trajectories in the evolution of class C and class D floral homeotic
      functions.
AB  - Duplicate genes may be retained by sub- and/or neofunctionalization through
      changes in gene expression and/or coding sequence, and therefore have the
      potential to contribute to the genetic robustness and diversification of an
      organism. In this study, two MADS-box genes were isolated from Taihangia
      rupestris, a core eudicot species belonging to the Rosaceae. Sequence and
      phylogenetic analyses revealed that they are clade members of the euAG and PLE
      lineages, respectively, and hence the two genes are named TrAG (Taihangia
      rupestris AGAMOUS) and TrSHP (Taihangia rupestris SHATTERPROOF). Southern blot
      analysis shows that TrSHP is a single-copy gene in the T. rupestris genome. In
      situ hybridization analyses show that both TrAG and TrSHP are mainly expressed in
      the stamens, carpels, and ovules. When the stamen primordia are firstly observed,
      TrAG is initially expressed in the floral meristem domain that will initiate
      stamens and carpels. In contrast, no TrSHP signal is observed at this
      developmental stage. At late stages of carpel development, TrAG expression is
      detected in the ovules, ovaries, and developing styles and stigmas, whereas TrSHP
      expression is tightly restricted to the ovules. The transgenic Arabidopsis plants
      containing 35S::TrAG and 35S::TrSHP, respectively, showed similar phenotypes,
      including homeotic conversions of sepals into carpelloid structures bearing
      ovules and petals into staminoid organs, and the fruits shattering prematurely
      along the dehiscence zone. In addition, the phenotype of the transgenic
      35S::TrSHP Arabidopsis plants revealed that perianth abscission was inhibited.
      Yeast two-hybrid assays indicated that TrAG can interact with TrSEP3, whereas
      TrSHP cannot. The data suggest that the euAG and PLE paralogs, TrAG and TrSHP,
      may have subfunctionalized and/or neofunctionalized through changes in expression
      patterns and accumulating variations in the coding regions. Taking these findings
      together with those available expression and functional data from Arabidopsis and
      other species, we conclude that the compensatory ways vary among the euAG and PLE
      lineage pairs in eudicot species.

PMID- 17227370
TI  - Heterochrony, cannibalism, and the evolution of viviparity in Salamandra
      salamandra.
AB  - The way in which novelties that lead to macroevolutionary events originate is a
      major question in evolutionary biology, and one that can be addressed using the
      fire salamander (Salamandra salamandra) as a model system. It is exceptional
      among amphibians in displaying intraspecific diversity of reproductive
      strategies. In S. salamandra, two distinct modes of reproduction co-occur: the
      common mode, ovoviviparity (females giving birth to many small larvae), and a
      phylogenetically derived reproductive strategy, viviparity (females producing
      only a few large, fully metamorphosed juveniles, which are nourished maternally).
      We examine the relationship between heterochronic modifications of the ontogeny
      and the evolution of the new reproductive mode in the fire salamander. The in
      vitro development of embryos of ovoviviparous and viviparous salamanders from
      fertilization to metamorphosis is compared, highlighting the key events that
      distinguish the two modes of reproduction. We identify the heterochronic events
      that, together with the intrauterine cannibalistic behavior, characterize the
      derived viviparous reproductive strategy. The ways in which evolutionary
      novelties can arise by modification of developmental programs can be studied in
      S. salamandra. Moreover, the variation in reproductive modes and the associated
      variation of sequences of development occur in neighboring, conspecific
      populations. Thus, S. salamandra is a unique biological system in which
      evolutionary developmental research questions can be addressed at the level of
      populations.

PMID- 17227372
TI  - Evaluation of the knowledge of tooth avulsion of school professionals from
      Adamantina, Sao Paulo, Brazil.
AB  - Tooth avulsion is common in children, and emergency management in these cases is
      critical. This management can be made, not only by a dentist but by people who
      are present where the accident occurs. Consequently, knowledge of tooth avulsion
      is fundamental for school professionals working with children. The purpose of the
      present study was to evaluate the knowledge of tooth avulsion of school
      professionals from Adamantina, Sao Paulo, Brazil. For that purpose a
      questionnaire, including questions regarding emergency procedures for tooth
      avulsion, was answered by 117 teachers. The results demonstrated that 75.2% of
      school professionals knew the importance of emergency management and 60.6% would
      look for a dentist for treatment of the cases; 18.8% would reimplant the tooth
      and 7.6% would keep it in milk. This study showed the lack of knowledge of
      teachers on tooth avulsion; educational campaigns are necessary to improve the
      emergency management of tooth avulsion.

PMID- 17227373
TI  - Knowledge of general practitioners dentists about the emergency management of
      dental avulsion in Curitiba, Brazil.
AB  - The prognosis of traumatized teeth in general and of avulsed teeth in particular
      depends on prompt and appropriate treatment. Management of traumatic injuries may
      be a challenge to the non-specialized dentist, as they may occur when dentists
      are least prepared for it. The objective of this research was to investigate the
      knowledge of general practitioner dentists about the emergency management of
      dental avulsion in Curitiba, PR, Brazil. A group of 250 professionals were
      interviewed. The questions were related to knowledge of how to treat traumatic
      avulsion of teeth. The results suggest that the level of knowledge on the
      management of dental avulsion of the general practitioners dentists in Curitiba
      is adequate.

PMID- 17227374
TI  - Mouthguards: difference in longitudinal dimensional stability between single- and
      double-laminated fabrication techniques.
AB  - Though the use of mouthguards (MGs) has increased with the increase in sporting
      activities, little is known about the influence of their fabrication methods on
      longitudinal dimensional stability. The objective of this study was to compare
      the difference in the longitudinal dimensional stability between single and
      laminated MGs. Single-layer MGs were made from a 4.0 mm thick ethylene vinyl
      acetate (EVA) sheet and laminated MGs were made from two 2.0 mm thick sheets of
      EVA. MGs were kept in a 37 degrees C water bath for 60 h, equivalent to the time
      period of 3-months inter-oral use. MG deformation was analyzed by measuring
      designated points on the MG border using a profile projector (J-12, Nikon Inc.,
      Tokyo, Japan) before and after the water immersion. A finite-element model was
      also created to examine the time course of stress accumulation during the sheet
      forming process using Finite Element software. Longitudinal deformation was
      smaller in the laminated MGs than in the single-layer MGs in the anterior area (P
      < 0.05). Finite element method (FEM) analysis also showed the largest stress
      accumulation in the anterior incisal area where deformations were mainly
      observed. Laminated double layer MGs have advantages over single-layer MGs in
      terms of longitudinal stability due to lower stress accumulation during the
      fabrication process.

PMID- 17227375
TI  - Effectiveness of mouthguards in reducing neurocognitive deficits following sports
      related cerebral concussion.
AB  - Although it is widely accepted that mouthguards decrease the incidence of dental
      injuries, there is a controversy among sports medicine professionals as to the
      effectiveness of mouthguards in decreasing the incidence or severity of sports
      related cerebral concussion (SRCC). While some experimental data suggest that
      this may be the case, there exist a number of reports suggesting that mouthguards
      do not serve this purpose. These conclusions have been drawn, however, without
      actually measuring the extent of neurocognitive dysfunction in athletes following
      sports-related concussion. The purpose of this study was to determine whether
      mouthguard use reduces the neurocognitive and symptomatic impairments that follow
      an injurious episode of SRCC. Preseason baseline data were collected as part of
      an ongoing clinical program that uses a computerized neurocognitive test to
      assess various faculties of brain function and symptoms reported at the time of
      testing. Follow-up testing from 180 student-athletes who had sustained an SRCC
      was analyzed for the purpose of this study. These athletes were separated into
      one of two groups: those who reported using mouthguards and those who did not.
      Neurocognitive testing was accomplished using the Immediate Post-Concussion and
      Assessment Test (ImPACT). Results suggest that neurocognitive deficits at the
      time of the athletes' first follow-up assessment did not differ between
      mouthguard users and non-users, suggesting that mouthguard use does little to
      reduce the severity of neurocognitive dysfunction and onset of symptoms following
      sports-related head trauma. However, an interesting finding in this study was
      that athletes experienced significantly lower neurocognitive test scores and
      reported higher symptom scores following SRCC regardless of mouthguard use. This
      emphasizes a thorough clinical evaluation of athletes that have sustained an
      SRCC. Although it was found in this study that mouthguard use does not decrease
      the severity of concussion, it is important to note that the use of mouthguards
      is paramount in reducing maxillofacial and dental trauma and their use should
      continue to be mandated by athletic associations and supported by all dental and
      sports medicine professionals.

PMID- 17227376
TI  - An in vitro study of the pH of three calcium hydroxide dressing materials.
AB  - Calcium hydroxide is widely used as a root canal dressing material because of its
      favorable alkalinizing effect. It has been suggested that the action comes from
      diffusion of hydroxyl ions through the apical foramen. The purpose of this in
      vitro study was to test the pH changes that occurred over a period of 30 days
      using a mixture of calcium hydroxide and distilled water and two commercial
      calcium hydroxide products in a simulated periapical environment. The materials
      were inserted in glass tubes closed at one end, which were placed in individual
      vials containing distilled water at a pH 7.4. Unfilled glass tubes were used as
      controls. Alkalinity changes of the medium were measured at 1 and 24 h and 15 and
      30 days. The alkalinizing properties of all materials showed a rapid increase at
      1 and 24 h followed by a continuous but more gradual increase from 15 to 30 days.
      The control tubes did not cause a change in pH of the medium, which remained at
      pH 7.4. At the end of the observation period, the alkalinizing properties of
      Calasept and Ultracal XS were significantly higher (P < 0.05) than the calcium
      hydroxide/distilled water paste.

PMID- 17227377
TI  - The effect of calcium hydroxide root filling on dentin fracture strength.
AB  - This in vitro study measured the effect of calcium hydroxide root filling on the
      microtensile fracture strength (MTFS) of teeth. A total of 40 extracted human
      disease-free permanent maxillary incisors were hand and rotary instrumented and
      vertically compacted with United States Pharmacopeia (USP) calcium hydroxide. The
      teeth were stored in a moist environment for 7, 28, and 84 days. As a control
      group, 10 teeth were vertically compacted with gutta percha and sealer. The MTFS
      of the teeth was measured (Mpa) using an Instron machine. Data were assessed
      statistically using an unpaired t-test (P value). The intracanal placement of
      calcium hydroxide weakened the MTFS of teeth by 13.9 Mpa per 77 days: an average
      of 0.157 MPa day-1. Between 7 and 84 days, the MTFS of the dentin was reduced by
      43.9%. This difference was statistically significant (P < 0.05). A statistical
      difference (P < 0.05) was observed between the mean MTFS of the calcium hydroxide
      filled dentin between 7 days (45.7 MPa) and 28 days (35.6 MPa) and also between 7
      and 84 days (31.8 MPa). There was also a significant difference (P < 0.05)
      between the MTFS of the calcium hydroxide-filled dentin after 84 days (31.8 MPa)
      and the gutta percha-filled dentin (41.3 MPa) when used as a control root filling
      material. The weakening of the dentin by 23-43.9% following root canal filling
      with calcium hydroxide provides compelling evidence to re-evaluate the daily
      usage of this material in endodontic therapy.

PMID- 17227378
TI  - Evaluation of dentin permeability after light activated internal dental
      bleaching.
AB  - The aim of this in vitro study was to assess quantitatively the dentin
      permeability of human teeth after intracoronal bleaching therapy with 35%
      hydrogen peroxide activated by LEDs, halogen lamp or using the walking bleach
      technique. Forty human maxillary central incisors had standard access cavities
      performed and the cervical thirds of the canals were prepared with Gates-Glidden
      drills up to a size 130. Roots were resected between the coronal and middle
      thirds and the apical portions were discarded. A glass ionomer, 2 mm thick
      cervical plug was placed inside the canal, at the cement-enamel junction level.
      Group I received 35% hydrogen peroxide gel activated by LEDs. Group II was
      submitted to 35% hydrogen peroxide gel activated by halogen lamp. Group III
      received 35% hydrogen peroxide gel and the walking bleach technique was followed.
      Group IV (control) received a dry cotton pellet inside the pulp chamber with
      temporary restoration. Dentinal permeability was quantified by copper ion
      penetration. Linear measurements were obtained by analysis of digital images
      under x 5 magnification. Mean values and SD for the experimental groups were: I,
      7.1% (+/-3.2%); II, 8.4% (+/-3.0%); III, 9.1% (+/-3.0%); IV, 1.3% (+/-2.8%). One
      way ANOVA was used to analyze the results. Results showed an increase of
      permeability values for groups I, II and III when compared to group IV (control);
      however, no statistical differences were found between the three tested bleaching
      techniques. It can be concluded that 35% hydrogen peroxide activated by LED,
      halogen lamp or used following the walking bleach technique produced similar
      increase in dentinal permeability.

PMID- 17227379
TI  - Influence of enamel matrix derivative (Emdogain) and sodium fluoride on the
      healing process in delayed tooth replantation: histologic and histometric
      analysis in rats.
AB  - Although it has already been shown that enamel matrix derivative (Emdogain)
      promotes periodontal regeneration in the treatment of intrabony periodontal
      defects, there is little information concerning its regenerative capacity in
      cases of delayed tooth replantation. To evaluate the alterations in the
      periodontal healing of replanted teeth after use of Emdogain, the central
      incisors of 24 Wistar rats (Rattus norvegicus albinus) were extracted and left on
      the bench for 6 h. Thereafter, the dental papilla and the enamel organ of each
      tooth were sectioned for pulp removal by a retrograde way and the canal was
      irrigated with 1% sodium hypochlorite. The teeth were assigned to two groups: in
      group I, root surface was treated with 1% sodium hypochlorite for 10 min
      (changing the solution every 5 min), rinsed with saline for 10 min and immersed
      in 2% acidulated-phosphate sodium fluoride for 10 min; in group II, root surfaces
      were treated in the same way as described above, except for the application of
      Emdogain instead of sodium fluoride. The teeth were filled with calcium hydroxide
      (in group II right before Emdogain was applied) and replanted. All animals
      received antibiotic therapy. The rats were killed by anesthetic overdose 10 and
      60 days after replantation. The pieces containing the replanted teeth were
      removed, fixated, decalcified and paraffin-embedded. Semi-serial 6-microm-thick
      sections were obtained and stained with hematoxylin and eosin for histologic and
      histometric analyses. The use of 2% acidulated-phosphate sodium fluoride provided
      more areas of replacement resorption. The use of Emdogain resulted in more areas
      of ankylosis and was therefore not able to avoid dentoalveolar ankylosis. It may
      be concluded that neither 2% acidulated-phosphate sodium fluoride nor Emdogain
      were able to prevent root resorption in delayed tooth replantation in rats.

PMID- 17227380
TI  - Reattachment of a fractured permanent molar cusp: a 12-month follow-up.
AB  - A posterior crown fracture due to acute trauma is an uncommon type of dental
      injury. This case report presents combined endodontic-bioadhesive treatment of a
      complicated crown fracture of a permanent molar due to a horse riding accident.
      Endodontic therapy was initiated following surgical removal of the fractured
      mesiolingual cusp, which was stored frozen until bonding procedures could be
      carried out. Subgingival and proximal contours of the missing cusp were
      maintained by an interim glass-ionomer restoration during endodontic therapy.
      Following root-canal obturation, the fractured cusp was reattached using a total
      etch adhesive and composite resin system. The patient was recalled at 1, 3, 6 and
      12 months, demonstrating excellent clinical and radiographic findings.

PMID- 17227381
TI  - Use of hydroxyapatite in tooth replantation radiographically followed up for 14
      years: a case report.
AB  - A lateral incisor was replanted 4 h after trauma. The tooth subsequently
      developed external root resorption treated with calcium hydroxide initially and
      with a hydroxyapatite root filling subsequently. Radiographs of the replanted
      tooth were obtained to follow up the patient for 14 years.

PMID- 17227382
TI  - Multidisciplinary treatment approach for crown fracture and crown-root fracture -
      a case report.
AB  - The increased incidence of traumatic injuries to anterior teeth is a consequence
      of leisure activities, where the most common injuries are crown fractures.
      Treatment of the dental trauma is complex and requires a comprehensive and
      accurate diagnostic and treatment plan. It is also important to consider the
      biological, functional, esthetic and economic aspects, as well as the patient's
      desire. The purpose of this article is to report a case that shows the
      multidisciplinary approach required to successfully manage the rehabilitation of
      a maxillary central incisor with a complex crown fracture and a maxillary lateral
      incisor, that at first presented an oblique crown-root fracture, and after the
      orthodontic extrusion, suffered a more apical new crown-root fracture.

PMID- 17227383
TI  - Segmental osteotomy to reposition multiple osseointegrated dental implants in the
      anterior maxilla in a trauma patient.
AB  - A 16-year-old young man had severe loss of alveolar bone and lost four teeth in
      the anterior maxilla because of traumatic injury in a traffic accident. To
      overcome the surgically compromised condition for implant rehabilitation, the
      deficient ridge was augmented by autogenous bone graft from the mandibular
      symphysis. The augmented ridge had much improvement in width but less in vertical
      height. Four implants were placed to gain initial osseointegration. Segmental
      osteotomy was performed to occlusally reposition the implants and bone for 5-mm
      in the anterior maxilla. After 2 years of clinical follow-up, the rehabilitation
      outcome is satisfactory and stable.

PMID- 17227384
TI  - Replantation and transplantation following avulsion of two maxillary incisors.
AB  - Here we describe replantation and transplantation as a treatment conducted in a
      16-year-old patient following a bicycle accident. An avulsed left central incisor
      in maxilla was replanted after extra-oral root canal treatment, and the lost
      right central incisor of the maxilla was replaced by a left lateral incisor of
      the mandible in the region of the fracture fissure. Follow-up examination at 34
      months showed validity of treatment, although slight evidence of replacement
      resorption in the transplanted and replanted teeth was revealed.

PMID- 17227386
TI  - Temperature compensation through systems biology.
AB  - Temperature has a strong influence on most individual biochemical reactions.
      Despite this, many organisms have the remarkable ability to keep certain
      physiological fluxes approximately constant over an extended temperature range.
      In this study, we show how temperature compensation can be considered as a
      pathway phenomenon rather than the result of a single-enzyme property. Using
      metabolic control analysis, it is possible to identify reaction networks that
      exhibit temperature compensation. Because most activation enthalpies are
      positive, temperature compensation of a flux can occur when certain control
      coefficients are negative. This can be achieved in networks with branching
      reactions or if the first irreversible reaction is regulated by a feedback loop.
      Hierarchical control analysis shows that networks that are dynamic through
      regulated gene expression or signal transduction may offer additional
      possibilities to bring the apparent activation enthalpies close to zero and lead
      to temperature compensation. A calorimetric experiment with yeast provides
      evidence that such a dynamic temperature adaptation can actually occur.

PMID- 17227385
TI  - Docosahexaenoic acid stabilizes soluble amyloid-beta protofibrils and sustains
      amyloid-beta-induced neurotoxicity in vitro.
AB  - Enrichment of diet and culture media with the polyunsaturated fatty acid
      docosahexaenoic acid has been found to reduce the amyloid burden in mice and
      lower amyloid-beta (Abeta) levels in both mice and cultured cells. However, the
      direct interaction of polyunsaturated fatty acids, such as docosahexaenoic acid,
      with Abeta, and their effect on Abeta aggregation has not been explored in
      detail. Therefore, we have investigated the effect of docosahexaenoic acid,
      arachidonic acid and the saturated fatty acid arachidic acid on monomer
      oligomerization into protofibrils and protofibril fibrillization into fibrils in
      vitro, using size exclusion chromatography. The polyunsaturated fatty acids
      docosahexaenoic acid and arachidonic acid at micellar concentrations stabilized
      soluble Abeta42 wild-type protofibrils, thereby hindering their conversion to
      insoluble fibrils. As a consequence, docosahexaenoic acid sustained amyloid-beta
      induced toxicity in PC12 cells over time, whereas Abeta without docosahexaenoic
      acid stabilization resulted in reduced toxicity, as Abeta formed fibrils.
      Arachidic acid had no effect on Abeta aggregation, and neither of the fatty acids
      had any protofibril-stabilizing effect on Abeta42 harboring the Arctic mutation
      (AbetaE22G). Consequently, AbetaArctic-induced toxicity could not be sustained
      using docosahexaenoic acid. These results provide new insights into the toxicity
      of different Abeta aggregates and how endogenous lipids can affect Abeta
      aggregation.

PMID- 17227387
TI  - Properties of pyranose dehydrogenase purified from the litter-degrading fungus
      Agaricus xanthoderma.
AB  - We purified an extracellular pyranose dehydrogenase (PDH) from the basidiomycete
      fungus Agaricus xanthoderma using ammonium sulfate fractionation and ion-exchange
      and hydrophobic interaction chromatography. The native enzyme is a monomeric
      glycoprotein (5% carbohydrate) containing a covalently bound FAD as its
      prosthetic group. The PDH polypeptide consists of 575 amino acids and has a
      molecular mass of 65 400 Da as determined by MALDI MS. On the basis of the
      primary structure of the mature protein, PDH is a member of the glucose-methanol
      choline oxidoreductase family. We constructed a homology model of PDH using the
      3D structure of glucose oxidase from Aspergillus niger as a template. This model
      suggests a novel type of bi-covalent flavinylation in PDH, 9-S-cysteinyl, 8-alpha
      N3-histidyl FAD. The enzyme exhibits a broad sugar substrate tolerance, oxidizing
      structurally different aldopyranoses including monosaccharides and
      oligosaccharides as well as glycosides. Its preferred electron donor substrates
      are D-glucose, D-galactose, L-arabinose, and D-xylose. As shown by in situ NMR
      analysis, D-glucose and D-galactose are both oxidized at positions C2 and C3,
      yielding the corresponding didehydroaldoses (diketoaldoses) as the final reaction
      products. PDH shows no detectable activity with oxygen, and its reactivity
      towards electron acceptors is rather limited, reducing various substituted
      benzoquinones and complexed metal ions. The azino-bis-(3-ethylbenzthiazolin-6
      sulfonic acid) cation radical and the ferricenium ion are the best electron
      acceptors, as judged by the catalytic efficiencies (k(cat)/K(m)). The enzyme may
      play a role in lignocellulose degradation.

PMID- 17227389
TI  - Development and implementation of new educational concepts in a dental
      curriculum.
AB  - The Academic Centre for Dentistry Amsterdam introduced a fully renewed 5-year
      dental curriculum in September 2003. In this article, the educational principles
      and didactic choices that form the basis of the curriculum development are
      presented and attention is given to the process of development and the
      implementation strategy that constitute such an important part of the success of
      introducing a new curriculum. Special characteristics of the new curriculum are
      the clinical training practice, professional conduct, the elective profiles and
      academic education. In clinical practice, groups of students from different
      levels run a group practice in which they learn to work together, delegate tasks,
      solve clinical problems and apply evidence-based dentistry. In the new curriculum
      students learn to conduct themselves as professionals. In the third and in the
      fifth year, students choose an elective profile oriented, respectively, on
      research and on clinical knowledge and skills. Academic education is an important
      spearhead in this curriculum in which students not only learn why research is
      important to dentistry but also how dentists can use research to their own
      benefit. In development and implementation, a stepwise approach was used in which
      as many people as logistically possible were involved.

PMID- 17227390
TI  - The effect of a community dental service outreach programme on the confidence of
      undergraduate students to treat children: a pilot study.
AB  - OBJECTIVE: To examine the effect of a community dental service (CDS) outreach
      teaching programme on undergraduates' confidence to undertake a range of
      paediatric dental procedures. METHOD: Eighteen final year dental students
      completed a questionnaire prior to, and following participation in an outreach
      teaching programme. At each time point, the students were asked to identify how
      confident they felt to carry out a range of procedures commonly encountered in
      the treatment of children, employing a Likert scale modified to comprise six
      points where a rating of 1 represented 'not at all confident' and a rating of 6
      'very confident'. RESULTS: The distribution of scores at each time point
      indicated that students were more confident to carry out each of the listed
      procedures following participation in the outreach teaching programme than they
      had been on completion of their paediatric dentistry sessions within the School
      of Dentistry. At the individual student level, 16 of the 18 students indicated
      that they were, overall, more confident following their placement than
      previously. CONCLUSIONS: It can be concluded that the long-established CDS
      outreach teaching programme run by the School of Dentistry, Wales College of
      Medicine in conjunction with the staff of Cardiff and Vale NHS Trust is a
      valuable adjunct to undergraduate teaching in paediatric dentistry.

PMID- 17227391
TI  - Evaluation of student and faculty perceptions of the PBL curriculum at two dental
      schools from a student perspective: a cross-sectional survey.
AB  - Problem-based learning (PBL) research has primarily highlighted issues related to
      medical education and less evaluation has been reported from the field of dental
      education. Furthermore, literature reports tend to focus mainly on PBL from a
      pedagogic and curriculum constructional view and up to this date, studies from a
      student perspective are lacking. The aim of this study was to approach the
      evaluation of student and staff perceptions of PBL curricula from a student
      perspective at two separate schools: the Faculty of Odontology at the University
      of Malmo, Sweden and the dental school of the University of Southern California,
      School of Dentistry (USCSD), Los Angeles, CA, USA. The study was initiated and
      conducted by two of the authors, at the time senior students at the Faculty of
      Odontology in Malmo, Sweden. The study was comprised of a literature search, a 2
      week field trip to USCSD, USA, survey distribution to students and faculty in
      both schools, analysis of the data and a written report for oral defence. The
      results from the survey were intended to provide feedback on student and faculty
      perceptions regarding the PBL curriculum. The results indicate a general student
      and faculty satisfaction with the PBL curriculum. Perhaps, surprisingly their
      perceptions did not differ significantly despite differences in geography,
      culture and implementation of PBL pedagogy.

PMID- 17227392
TI  - An audit to assess the outcome of a 1-day acupuncture course for dentists.
AB  - OBJECTIVE: The principal author has, during the last 4 years, given 45 1-day
      courses in acupuncture involving 450 dentists arranged under the umbrella of
      continuous post-graduate dental education. There is a paucity of evidence in the
      published dental literature regarding the outcomes after such courses, and the
      objective of this work was to analyse the outcome after a 1-day acupuncture
      course. MATERIALS AND METHODS: In co-operation with the individual post-graduate
      centres, a questionnaire was posted to all participants to ascertain whether; (a)
      the dentist has taken up acupuncture; (b) how often acupuncture was used; (c) any
      reasons for not incorporating acupuncture into the daily practice. To further
      evaluate the quality of the course, the following questions were addressed; (d)
      overall rating of the course; (e) the relevance of the course, assessed on a
      scale from 1 to 6 (1, highly unfavourable; 6, very high favourable). MAIN
      OUTCOME: A total of 209 (51.6%) questionnaires were returned, although 15 (3.7%)
      were subsequently excluded. The male:female ratio of respondents was 3:2, with an
      average age of 42 and 19 years of experience in dental practice. As many as 46%
      of respondents had incorporated acupuncture into their practice and 19% reported
      using acupuncture several times a month. The conditions treated were control of
      the gag reflex, stress management, sinusitis, headache and facial pain. The main
      reasons for not taking up acupuncture was 'the dentist never actually got round
      to starting' (83%) and lack of appropriate patients (60%). Regarding the
      evaluation of the course, the assessment forms were obtained from 47% of the
      participants. Participants from all centres rated the course in the top end, 5.3
      of 6.0 possible.

PMID- 17227393
TI  - Validity and reliability of patient satisfaction questionnaires in a dental
      school in Japan.
AB  - PURPOSE: The purpose of this study was to construct questionnaires for the dental
      school setting from freely given patient answers with the aid of text mining, and
      to confirm the structure, reliability and validity of the questionnaires.
      METHODS: Using these questionnaires, we carried out a survey of the satisfaction
      of patients treated at the Dental Hospital of the Tsurumi University School of
      Dental Medicine. A total of 3394 patients participated in the study. To confirm
      the reliability of inter-item correlations and construct validity, factor
      analysis was carried out, and items belonging to each factor and Cronbach's alpha
      coefficients were calculated. RESULTS: Four factors were extracted and 64.0% of
      the variance was explained by these four factors. All correlation coefficients
      were >0.85. These four factors were: 'Treatment', 'Communication', 'Facilities'
      and 'Appearances'. From structural equation modelling, we determined that overall
      satisfaction was >0.75 and was statistically significant. CONCLUSION: The
      questionnaires used in this study are useful for measuring patient satisfaction
      in the dental school hospital setting.

PMID- 17227394
TI  - Comparison between computer-aided testing and traditional multiple choice: an
      equivalence study.
AB  - AIMS: Computer-aided learning (CAL) is a viable alternative to traditional
      teaching methods. While CAL is used for teaching only, computer-aided testing
      (CAT) can be applied as a computer-based examination method. The aim of the
      present study was to compare the performance of undergraduate students in
      computer-interactive tests and traditional multiple choice tests and to evaluate
      the influence of question length and language skills on test results. MATERIALS
      AND METHODS: Fifty-two native German-speaking students and five non-native
      speaking students were randomly assigned to two groups. They were required to
      answer 20 conventional multiple choice questions and 20 questions using the
      interactive MobiTed system. An analysis of variance and t-tests (alpha = 0.05)
      were used to compare scores. RESULTS: Non-native speakers scored significantly
      lower on the interactive test compared with the native speaking students (P =
      0.048 for long questions and P = 0.003 for short questions). There were no
      significant group differences on the conventional multiple choice test (P = 0.052
      for long questions and P = 0.089 for short questions). Based on the results of
      the native speaking students neither test method nor question length had an
      influence on overall performance. CONCLUSION: Interactive multiple choice tests
      may provide an alternative to written tests, especially when considering time
      expenditure. Language skills and question length should be taken into account
      when setting time limits for examination.

PMID- 17227395
TI  - Oral health behaviour and its determinants amongst Iranian dental students.
AB  - OBJECTIVES: To study the oral health behaviour (OHB) of Iranian senior dental
      students in relation to their gender, background characteristics, knowledge of
      preventive care, and attitudes towards preventive dentistry. MATERIALS AND
      METHODS: Using a cluster random sampling approach, a questionnaire survey was
      conducted with 327 senior dental students in seven dental schools. The
      questionnaire covered age, gender, parents' employment in dentistry, previous
      academic education in dental hygiene, oral self-care, most recent dental check
      up, knowledge of preventive dentistry and attitudes towards it. Attending a
      dental check-up by a dentist or a classmate within the last year was defined as
      preventive care use. Chi-square test and logistic regression models were used for
      statistical analyses. RESULTS: Women reported significantly higher frequencies of
      tooth brushing (P < 0.001), fluoridated toothpaste use (P = 0.001) and flossing
      (P < 0.001) compared with men. Respondents who had been previously educated as
      dental hygienists had lower frequencies of eating sugary snacks (P < 0.001) and
      paid more attention to preventive care (P = 0.03) than others. Those with more
      extensive knowledge of preventive care reported higher frequencies of using
      fluoridated toothpaste (P = 0.05). Reported frequencies of brushing were higher
      amongst those with more positive attitudes (P = 0.03). In logistic regression
      models, having at least one parent employed as a dentist was significantly
      associated with higher frequencies of eating sugary snacks (P = 0.047, OR = 0.3)
      and more frequent preventive care use (P = 0.048, OR = 2.9). CONCLUSION:
      Education and training in preventive measures should be effective enough to
      overcome background characteristics. There is room for improving the OHB of
      Iranian dental students.

PMID- 17227397
TI  - The introduction of a new assessment system in restorative dentistry: the
      undergraduate and patient experience.
AB  - In 2000, the University of Bristol Dental School Division of Restorative
      Dentistry carried out a review of the assessment methods used within the
      undergraduate programme. Following this review, a number of key recommendations
      were made and the system of formative assessment within the division was changed.
      Audits were conducted immediately prior to the introduction of the new system and
      2 years after it had been introduced, the results of these audits are presented.
      There was no change in the number of failed appointments between the initial
      audit and the second audit. There was a reduction in the number of patients
      treated by more than one student from 25% to 14% (approximating to 3% if student
      withdrawal from the course is taken into account). The length of time taken to
      complete treatment reduced between the two audits with more than half of all
      patients having their treatment completed within 3 months of their initial
      examination in the second audit. Ninety-five percent of treatment plans were
      completed in the second audit compared with only 62% in the first audit. In the
      second audit, the outstanding 5% of cases were signed off as incomplete for
      satisfactory reasons by the member of supervisory staff (e.g. patients who had
      moved away or were discharged due to poor attendance). Student comments were
      mostly positive, the small number of negative comments related to some students
      being confused by the paperwork in the new system. The overall process has been
      an extremely positive experience which has resulted in an assessment system with
      increased clarity which appears to have reduced the stress levels reported by the
      undergraduate students on the programme and improved the quality of patient care
      within restorative dentistry.

PMID- 17227396
TI  - Prevention-oriented practice of Iranian senior dental students.
AB  - OBJECTIVES: To investigate self-reported preventive practice of Iranian senior
      dental students in dental caries management. SUBJECTS AND METHODS: To obtain an
      estimated sample size of 250 subjects, seven state dental schools were selected
      based on a stratified random sampling approach. All the senior dental students (n
      = 327) were asked to voluntarily fill in a self-administered pre-tested
      questionnaire during the spring term in 2005. In the questionnaire two
      hypothetical patient cases (a high-risk and a low-risk patient) were presented
      and the students were asked to express their conceptions on a five-point Likert
      scale about including each of nine given alternatives in the patients' treatment
      plans. The respondents' self-reported oral self-care (OSC), preventive knowledge,
      attitude towards prevention and self-perceived competency in giving preventive
      care were also assessed. Chi-squared test and logistic regression model served
      for statistical analyses. RESULTS: A total of 270 students filled in the
      questionnaire (response rate = 82%). Acquiring high scores of preventive practice
      as assessed by patient cases was found to be more frequent among those reporting
      recommended OSC (P = 0.007) and those with higher attitude scores (P < 0.001).
      Also, those reporting being competent in giving preventive care had higher scores
      of preventive practice compared with the others (P = 0.02). In the regression
      model, recommended OSC (P = 0.05, OR = 1.9) and positive attitudes towards
      preventive dentistry (P = 0.001, OR = 3.3) showed significant association with
      acquiring highest scores of preventive practice. CONCLUSION: To improve their
      preventive practice in the future, more emphasis should be placed on the dental
      students' own oral health behaviour and attitudes related to it.

PMID- 17227398
TI  - Theory and the microbial world.

PMID- 17227399
TI  - The searchlight and the bucket of microbial ecology.

PMID- 17227400
TI  - The human microbiome: eliminating the biomedical/environmental dichotomy in
      microbial ecology.

PMID- 17227401
TI  - Riding giants.

PMID- 17227402
TI  - The future of single-cell environmental microbiology.

PMID- 17227403
TI  - Moving to a higher level of abstraction.

PMID- 17227404
TI  - Single-cell genomics.

PMID- 17227405
TI  - The importance of individuals and scale: moving towards single cell microbiology.

PMID- 17227406
TI  - Real-time microbial ecology.

PMID- 17227407
TI  - Data storm.

PMID- 17227408
TI  - The effect of Photorhabdus luminescens (Enterobacteriaceae) on the survival,
      development, reproduction and behaviour of Caenorhabditis elegans (Nematoda:
      Rhabditidae).
AB  - The free-living soil nematode Caenorhabditis elegans interacts with diverse
      microorganisms in its natural habitat. These microorganisms may serve as a food
      source or represent a harmful threat. As such, they constitute one of the most
      important ecological factors of the worm's natural environment. In this study, we
      examined the interaction between two natural isolates of C. elegans and three
      natural isolates of the entomopathogenic bacterium Photorhabdus luminescens. Two
      of the tested P. luminescens strains were clearly pathogenic. They consistently
      reduced the worm's developmental, survival and reproductive rate, most likely
      through the production of nematicidal compounds. The third natural isolate tested
      did not decrease worm fitness. These differences could be associated with a
      deletion of one gene (tcdA4) ( approximately 7kb) of the toxin complex D
      pathogenicity island, which was found in only the non-pathogenic strain. Our
      study additionally highlights the importance of behaviour in defence.
      Caenorhabditis elegans showed two distinct avoidance behaviours towards the
      pathogenic but not the non-pathogenic P. luminescens strains. In particular,
      nematodes physically escaped and also reduced the ingestion of pathogenic
      bacteria. Our results strongly suggest that C. elegans possesses the capacity to
      distinguish between and subsequently respond to harmful and non-harmful strains
      of the same bacterial species. The underlying mechanisms of such interactions are
      currently unknown. Their dissection will represent a major challenge for future
      research and should enhance our knowledge of the ecology of this important model
      organism in biological research.

PMID- 17227409
TI  - Diversity of phototrophic bacteria in microbial mats from Arctic hot springs
      (Greenland).
AB  - We investigated the genotypic diversity of oxygenic and anoxygenic phototrophic
      microorganisms in microbial mat samples collected from three hot spring
      localities on the east coast of Greenland. These hot springs harbour unique
      Arctic microbial ecosystems that have never been studied in detail before.
      Specific oligonucleotide primers for cyanobacteria, purple sulfur bacteria, green
      sulfur bacteria and Choroflexus/Roseiflexus-like green non-sulfur bacteria were
      used for the selective amplification of 16S rRNA gene fragments. Amplification
      products were separated by denaturing gradient gel electrophoresis (DGGE) and
      sequenced. In addition, several cyanobacteria were isolated from the mat samples,
      and classified morphologically and by 16S rRNA-based methods. The cyanobacterial
      16S rRNA sequences obtained from DGGE represented a diverse, polyphyletic
      collection of cyanobacteria. The microbial mat communities were dominated by
      heterocystous and non-heterocystous filamentous cyanobacteria. Our results
      indicate that the cyanobacterial community composition in the samples were
      different for each sampling site. Different layers of the same heterogeneous mat
      often contained distinct and different communities of cyanobacteria. We observed
      a relationship between the cyanobacterial community composition and the in situ
      temperatures of different mat parts. The Greenland mats exhibited a low diversity
      of anoxygenic phototrophs as compared with other hot spring mats which is
      possibly related to the photochemical conditions within the mats resulting from
      the Arctic light regime.

PMID- 17227410
TI  - Kleptoplasty in an Antarctic dinoflagellate: caught in evolutionary transition?
AB  - Photosynthetic dinoflagellates contain a diverse collection of plastid types, a
      situation believed to have arisen from multiple endosymbiotic events. In
      addition, a number of heterotrophic (phagotrophic) dinoflagellates possess the
      ability to acquire chloroplasts temporarily by engulfing algae and retaining
      their chloroplasts in a functional state. These latter relationships typically
      last from a few days to weeks, at which point the chloroplasts lose function, are
      digested and replaced with newly acquired plastids. A novel and abundant
      dinoflagellate related to the icthyotoxic genera Karenia and Karlodinium was
      recently discovered by us in the Ross Sea, Antarctica. Sequencing of its plastid
      small subunit ribosomal gene indicated that it did not share evolutionary history
      with the plastids of Karenia or Karlodinium, but was closely related to the free
      living haptophyte Phaeocystis antarctica, a species that often dominates
      phytoplankton blooms in the Ross Sea. Chloroplast uptake was observed to occur
      rapidly (within 2 days), with retention in cultures being long-lived (several
      months) but not permanent. The dinoflagellate was also incapable of growing
      indefinitely in continuous darkness with algae as prey. Our findings may indicate
      an emerging endosymbiotic event yielding a dinoflagellate that is presently
      neither purely phototrophic nor purely heterotrophic, but occupies a niche
      juxtaposed between these contrasting nutritional modes.

PMID- 17227411
TI  - Bacterial community shifts in organically perturbed sediments.
AB  - Bacterial abundance, diversity and sediment function were investigated in
      organically perturbed sediments under Tasmanian salmon (Salmo salar) farms and
      adjacent reference sites. Bacterial numbers increased as farming and organic
      loading progressed through the farm stocking cycle and declined during the fallow
      period, although not to prestocking levels. Bacterial numbers ranged between
      approximately 2 x 10(8) and 3 x 10(9) cells per gram of sediment and were higher
      at cage sites than reference sites. Microelectrode and respiration data also
      demonstrated a clear effect of organic loading on sediments. Denaturing gradient
      gel electrophoresis (DGGE) showed that bacterial communities shifted both in
      response to farm loading and its cessation. A seasonal effect on microbial
      communities was also evident. Although bacterial communities did shift again
      during the fallowing period, this shift was not necessarily a return to
      preloading communities. The complexity of community shifts may be affected by the
      vast functional redundancy of bacterial groups. All bacterial communities,
      including those at reference sites, were highly dynamic. Respiration studies of
      amended sediments indicated that fish farm sediments were at least as resilient
      and diverse as reference site communities. The results of this study indicate
      that the functional redundancy of highly complex bacterial communities
      contributes to their robustness. The relationship between diversity and stability
      in bacterial communities remains unclear and requires further investigation
      before an understanding of bacterial response to perturbation is possible.

PMID- 17227412
TI  - Unveiling fungal zooflagellates as members of freshwater picoeukaryotes: evidence
      from a molecular diversity study in a deep meromictic lake.
AB  - This study presents an original 18S rRNA PCR survey of the freshwater
      picoeukaryote community, and was designed to detect unidentified heterotrophic
      picoflagellates (size range 0.6-5 microm) which are prevalent throughout the year
      within the heterotrophic flagellate assemblage in Lake Pavin. Four clone
      libraries were constructed from samples collected in two contrasting zones in the
      lake. Computerized statistic tools have suggested that sequence retrieval was
      representative of the in situ picoplankton diversity. The two sampling zones
      exhibited similar diversity patterns but shared only about 5% of the operational
      taxonomic units (OTUs). Phylogenetic analysis clustered our sequences into three
      taxonomic groups: Alveolates (30% of OTUs), Fungi (23%) and Cercozoa (19%). Fungi
      thus substantially contributed to the detected diversity, as was additionally
      supported by direct microscopic observations of fungal zoospores and sporangia. A
      large fraction of the sequences belonged to parasites, including Alveolate
      sequences affiliated to the genus Perkinsus known as zooparasites, and chytrids
      that include host-specific parasitic fungi of various freshwater phytoplankton
      species, primarily diatoms. Phylogenetic analysis revealed five novel clades that
      probably include typical freshwater environmental sequences. Overall, from the
      unsuspected fungal diversity unveiled, we think that fungal zooflagellates have
      been misidentified as phagotrophic nanoflagellates in previous studies. This is
      in agreement with a recent experimental demonstration that zoospore-producing
      fungi and parasitic activity may play an important role in aquatic food webs.

PMID- 17227413
TI  - Assessment of anaerobic benzene degradation potential using 16S rRNA gene
      targeted real-time PCR.
AB  - Benzene is a common groundwater pollutant that is often recalcitrant under the
      anaerobic conditions that prevail at hydrocarbon-contaminated aquifers. Thus,
      determining the potential for anaerobic benzene degradation is important to
      assess the feasibility of intrinsic bioremediation. In this work we developed a
      16S rRNA biomarker to estimate the concentration of putative benzene degraders in
      a methanogenic consortium that has been enriched on benzene for several years.
      Primers were designed based on phylogenetic information from this consortium. The
      primers and probe were obtained by sequencing the dominant denaturing gradient
      gel electrophoresis band of this consortium, which corresponded to
      Desulfobacterium sp. clone OR-M2. No hybridization was observed with DNA samples
      from negative controls (i.e. toluene-degrading and dehalorespiring methanogenic
      consortia that do not degrade benzene). Samples from an anaerobic aquifer column
      that was bioaugmented with this benzene-degrading consortium showed a strong
      correlation between benzene degradation activity and the concentration of the
      target organism. Although our data do not prove that Desulfobacterium sp. is a
      benzene degrader, its enrichment as a result of benzene consumption and its
      correlation to anaerobic benzene degradation activity suggest that it either
      initiates benzene degradation or is a critical (commensal) partner. Therefore,
      the utility of this primers and probe set to assess anaerobic benzene degradation
      potential was demonstrated. This is the first report of the use of real-time
      quantitative PCR for forensic analysis of anaerobic benzene degradation. Whether
      this biomarker will be adequately selective and broadly applicable to assess
      benzene degradation potential under strongly anaerobic (sulfate reducing and
      methanogenic) conditions will require further research.

PMID- 17227414
TI  - Autotrophic CO2 fixation via the reductive tricarboxylic acid cycle in different
      lineages within the phylum Aquificae: evidence for two ways of citrate cleavage.
AB  - Autotrophic carbon fixation was characterized in representative members of the
      three lineages of the bacterial phylum Aquificae. Enzyme activity measurements
      and the detection of key genes demonstrated that Aquificae use the reductive
      tricarboxylic acid (TCA) cycle for autotrophic CO(2) fixation. This is the first
      time that strains of the Hydrogenothermaceae and 'Desulfurobacteriaceae' have
      been investigated for enzymes of autotrophic carbon fixation. Unexpectedly, two
      different mechanisms of citrate cleavage could be identified within the
      Aquificae. Aquificaceae use citryl-CoA synthetase and citryl-CoA lyase, whereas
      Hydrogenothermaceae and 'Desulfurobacteriaceae' use ATP citrate lyase. The first
      mechanism is likely to represent the ancestral version of the reductive TCA
      cycle. Sequence analyses further suggest that ATP citrate lyase formed by a gene
      fusion of citryl-CoA synthetase and citryl-CoA lyase and subsequently became
      involved in a modified version of this pathway. However, rather than having
      evolved within the Aquificae, our phylogenetic analyses indicate that Aquificae
      obtained their ATP citrate lyase through lateral gene transfer. Aquificae play an
      important role in biogeochemical processes in a variety of high-temperature
      habitats. Thus, these findings substantiate the hypothesis that autotrophic
      carbon fixation through the reductive TCA cycle is widespread and contributes
      significantly to biomass production particularly in hydrothermal habitats.

PMID- 17227415
TI  - Microbial diversity and dynamics in multi- and single-compartment anaerobic
      bioreactors processing sulfate-rich waste streams.
AB  - We investigated bacterial and archaeal community structures and population
      dynamics in two anaerobic bioreactors processing a carbohydrate- and sulfate-rich
      synthetic wastewater. A five-compartment anaerobic migrating blanket reactor
      (AMBR) was designed to promote biomass and substrate staging, which partially
      separates the processes of methanogenesis and sulfidogenesis in the middle and
      outer compartment(s) respectively. The second reactor was a conventional, single
      compartment upflow anaerobic sludge blanket (UASB) reactor. Both reactors, which
      were seeded with the same inoculum, performed well when the influent chemical
      oxygen demand (COD)/SO(4) (2-) mass ratio was 24.4. The AMBR performed worse than
      the UASB reactor when the influent COD/SO(4) (2-) mass ratio was decreased to 5.0
      by raising the sulfate load. Terminal restriction fragment length polymorphism
      analyses of bacterial 16S rRNA genes showed that the increase in sulfate load had
      a greater impact on bacterial diversity and community structure for the five AMBR
      compartments than for the UASB reactor. Moreover, bacterial community profiles
      across AMBR compartments became more similar through time, indicating a
      converging, rather than a staged community. While similar populations were
      abundant in both reactors at the beginning of the experiment, fermenting bacteria
      (clostridia, streptococci), and sulfate-reducing bacteria became more abundant in
      the AMBR, after shifting to a higher sulfate load, while a novel Thermotogales
      like population eventually became predominant in the UASB reactor. A similar
      shift in the community structure of the hydrogenotrophic methanogens in the AMBR
      occurred: representatives of the Methanobacteriaceae out-competed the
      Methanospirillaceae after increasing the sulfate load in the AMBR, while the
      archaeal community structure was maintained in the UASB.

PMID- 17227416
TI  - Abundance, distribution and potential activity of methane oxidizing bacteria in
      permafrost soils from the Lena Delta, Siberia.
AB  - The methane oxidation potential of active layer profiles of permafrost soils from
      the Lena Delta, Siberia, was studied with regard to its respond to temperature,
      and abundance and distribution of type I and type II methanotrophs. Our results
      indicate vertical shifts within the optimal methane oxidation temperature and
      within the distribution of type I and type II methanotrophs. In the upper active
      layer, maximum methane oxidation potentials were detected at 21 degrees C. Deep
      active layer zones that are constantly exposed to temperatures below 2 degrees C
      showed a maximum potential to oxidize methane at 4 degrees C. Our results
      indicate a dominance of psychrophilic methanotrophs close to the permafrost
      table. Type I methanotrophs dominated throughout the active layer profiles but
      their number strongly fluctuated with depth. In contrast, type II methanotrophs
      were constantly abundant through the whole active layer and displaced type I
      methanotrophs close to the permafrost table. No correlation between in situ
      temperatures and the distribution of type I and type II methanotrophs was found.
      However, the distribution of type I and type II methanotrophs correlated
      significantly with in situ methane concentrations. Beside vertical fluctuations,
      the abundance of methane oxidizers also fluctuated according to different
      geomorphic units. Similar methanotroph cell counts were detected in samples of a
      flood plain and a polygon rim, whereas cell counts in samples of a polygon centre
      were up to 100 times lower.

PMID- 17227418
TI  - Diversity and abundance of sulfate-reducing microorganisms in the sulfate and
      methane zones of a marine sediment, Black Sea.
AB  - The Black Sea, with its highly sulfidic water column, is the largest anoxic basin
      in the world. Within its sediments, the mineralization of organic matter occurs
      essentially through sulfate reduction and methanogenesis. In this study, the
      sulfate-reducing community was investigated in order to understand how these
      microorganisms are distributed relative to the chemical zonation: in the upper
      sulfate zone, at the sulfate-methane transition zone, and deeply within the
      methane zone. Total bacteria were quantified by real-time PCR of 16S rRNA genes
      whereas sulfate-reducing microorganisms (SRM) were quantified by targeting their
      metabolic key gene, the dissimilatory (bi)sulfite reductase (dsrA). Sulfate
      reducing microorganisms were predominant in the sulfate zone but occurred also in
      the methane zone, relative proportion was maximal around the sulfate-methane
      transition, c. 30%, and equally high in the sulfate and methane zones, 5-10%. The
      dsrAB clone library from the sulfate-methane transition zone, showed mostly
      sequences affiliated with the Desulfobacteraceae. While, the dsrAB clone
      libraries from the upper, sulfate-rich zone and the deep, sulfate-poor zone were
      dominated by similar, novel deeply branching sequences which might represent Gram
      positive spore-forming sulfate- and/or sulfite-reducing microorganisms. We thus
      hypothesize that terminal carbon mineralization in surface sediments of the Black
      Sea is largely due to the sulfate reduction activity of previously hidden SRM.
      Although these novel SRM were also abundant in sulfate-poor, methanogenic areas
      of the Black Sea sediment, their activities and possibly very versatile metabolic
      capabilities remain subject of further study.

PMID- 17227417
TI  - Analysis of nitrite reductase (nirK and nirS) genes and cultivation reveal
      depauperate community of denitrifying bacteria in the Black Sea suboxic zone.
AB  - Chemical profiles of the Black Sea suboxic zone show a distribution of nitrogen
      species which is traditionally associated with denitrification, i.e. a secondary
      nitrite maximum associated with nitrate depletion and a N(2) gas peak. To better
      understand the distribution and diversity of the denitrifier community in the
      Black Sea suboxic zone, we combined a cultivation approach with cloning and
      sequencing of PCR-amplified nitrite reductase (nirS and nirK) genes. The Black
      Sea suboxic zone appears to harbour a homogeneous community of denitrifiers. For
      nirK, over 94% of the sequences fell into only three distinct phylogenetic
      clusters, and for nirS, a single closely related sequence type accounted for 91%
      of the sequences retrieved. Both nirS and nirK genes showed a dramatic shift in
      community composition at the bottom of the suboxic zone, but overall, nirK-based
      community composition showed much greater variation across depths compared with
      the highly uniform distribution of nirS sequences throughout the suboxic zone.
      The dominant nirK and nirS sequences differed at the amino acid level by at least
      17% and 8%, respectively, from their nearest database matches. Denitrifying
      isolates recovered from the suboxic zone shared 97% 16S rRNA gene sequence
      similarity with Marinobacter maritimus. Analysis of the recently discovered nirS
      gene from the anammox bacterium Candidatus'Kuenenia stuttgartiensis' revealed
      that mismatches with commonly used primers may have prevented the previous
      detection of this divergent sequence.

PMID- 17227419
TI  - Abundance of six tetracycline resistance genes in wastewater lagoons at cattle
      feedlots with different antibiotic use strategies.
AB  - The abundance of six tetracycline resistance genes tet(O), tet(Q), tet(W),
      tet(M), tet(B) and tet(L), were quantified over time in wastewater lagoons at
      concentrated animal feeding operations (CAFO) to assess how feedlot operation
      affects resistance genes in downstream surface waters. Eight lagoons at five
      cattle feedlots in the Midwestern United States were monitored for 6 months.
      Resistance and 16S-rRNA gene abundances were quantified using real-time PCR, and
      physicochemical lagoon conditions, tetracycline levels, and other factors (e.g.
      feedlot size and weather conditions) were monitored over time. Lagoons were
      sorted according to antibiotic use practice at each site, and designated as 'no
      use', 'mixed-use' or 'high-use' for comparison. High-use lagoons had
      significantly higher detected resistance gene levels (tet(R); 2.8 x 10(6) copies
      ml(-1)) relative to no-use lagoons (5.1 x 10(3) copies ml(-1); P < 0.01) and
      mixed-use lagoons (7.3 x 10(5) copies ml(-1); P = 0.076). Bivariate correlation
      analysis on pooled data (n = 54) confirmed that tet(R) level strongly correlated
      with feedlot area (r = 0.67, P < 0.01) and 'total' bacterial 16S-rRNA gene level
      in each lagoon (r = 0.51, P < 0.01), which are both characteristic of large
      CAFOs. tet(M) was the most commonly detected gene, both in absolute number and
      normalized to 16S-rRNA gene level, although tet(O), tet(Q) and tet(W) levels were
      also high in the mixed and high-use lagoons. Finally, resistance gene levels were
      highly seasonal with abundances being 10-100 times greater in the autumn versus
      the summer. Results show that antibiotic use strategy strongly affects both the
      abundance and seasonal distribution of resistance genes in associated lagoons,
      which has implications on water quality and feedlot management practices.

PMID- 17227420
TI  - Isolation and gene quantification of heterotrophic N2-fixing bacterioplankton in
      the Baltic Sea.
AB  - Cyanobacteria are regarded as the main N(2)-fixing organisms in marine waters.
      However, recent clone libraries from various oceans show a wide distribution of
      the dinitrogenase reductase gene (nifH) originating from heterotrophic
      bacterioplankton. We isolated heterotrophic N(2)-fixing bacteria from Baltic Sea
      bacterioplankton using low-nitrogen plates and semi-solid diazotroph medium
      (SSDM) tubes. Isolates were analysed for the nitrogenase (nifH) gene and active
      N(2) fixation by nested polymerase chain reaction (PCR) and acetylene reduction
      respectively. A primer-probe set targeting the nifH gene from a gamma
      proteobacterial isolate, 97% 16S rDNA similarity to Pseudomonas stutzeri, was
      designed for measuring in situ dynamics using quantitative real-time PCR. This
      nifH gene sequence was detected at two of 11 stations in a Baltic Proper transect
      at abundances of 3 x 10(4) and 0.8 x 10(3) copies per litre seawater
      respectively. Oxygen requirements of isolates were examined by cultivation in
      SSDM tubes where oxygen gradients were determined with microelectrodes. Growth,
      and thereby N(2) fixation, was observed as horizontal bands formed at oxygen
      levels of 0-6% air saturation. The apparent microaerophilic or facultative
      anaerobic nature of the isolates explains why the SSDM approach is the most
      appropriate isolation method. Our study illustrates how combined isolation,
      functional analyses and in situ quantification yielded insights into the oxygen
      requirements of heterotrophic N(2)-fixing bacterioplankton isolates, which were
      confirmed to be present in situ.

PMID- 17227421
TI  - Determining the identity and roles of oil-metabolizing marine bacteria from the
      Thames estuary, UK.
AB  - Crude oil is a complex mixture of different hydrocarbons. While diverse bacterial
      communities can degrade oil, the specific roles of individual members within such
      communities remain unclear. To identify the key bacterial taxa involved in
      aerobic degradation of specific hydrocarbons, microcosm experiments were
      established using seawater from Stanford le Hope, Thames estuary, UK, adjacent to
      a major oil refinery. In all microcosms, hydrocarbon degradation was significant
      within 10 weeks, ranging from > 99% of low-molecular-weight alkanes (C(10)
      C(18)), 41-84% of high-molecular-weight alkanes (C(20)-C(32)) and pristane, and
      32-88% of polycyclic aromatic hydrocarbons (PAHs). Analysis of 16S rRNA sequences
      from clone libraries and denaturing gradient gel electrophoresis (DGGE) indicated
      that, except when incubated with fluorene, PAH-degrading communities were
      dominated by Cycloclasticus. Moreover, PAH-degrading communities were distinct
      from those in microcosms containing alkanes. Degradation of the branched alkane,
      pristane, was carried out almost exclusively by Alcanivorax. Bacteria related to
      Thalassolituus oleivorans (99-100% identity) were the dominant known alkane
      degraders in n-alkane (C(12)-C(32)) microcosms, while Roseobacter-related
      bacteria were also consistently found in these microcosms. However, in contrast
      to previous studies, Thalassolituus, rather than Alcanivorax, was dominant in
      crude oil-enriched microcosms. The communities in n-decane microcosms differed
      from those in microcosms supplemented with less volatile alkanes, with a
      phylogenetically distinct species of Thalassolituus out-competing T. oleivorans.
      These data suggest that the diversity and importance of the genus Thalassolituus
      is greater than previously established. Overall, these experiments demonstrate
      how degradation of different petroleum hydrocarbons is partitioned between
      different bacterial taxa, which together as a community can remediate petroleum
      hydrocarbon-impacted estuarine environments.

PMID- 17227422
TI  - Effects of temperature and biostimulation on oil-degrading microbial communities
      in temperate estuarine waters.
AB  - Improved strategies for oil-spill remediation will follow a better understanding
      of the nature, activities and regulating parameters of petroleum hydrocarbon
      degrading microbial communities in temperate marine environments. The addition of
      crude oil to estuarine water resulted in an immediate change in bacterial
      community structure, increased abundance of hydrocarbon-degrading microorganisms
      and a rapid rate of oil degradation, suggesting the presence of a pre-adapted oil
      degrading microbial community and sufficient supply of nutrients. Relatively
      rapid degradation was found at 4 degrees C, the lowest temperature tested; and it
      was temperature rather than nutrient addition that most influenced the community
      structure. A detailed phylogenetic analysis of oil-degrading microcosms showed
      that known hydrocarbonoclastic organisms like Thalassolituus and Cycloclasticus,
      as well as proposed oil degraders like Roseobacter, were present at both 4
      degrees C and 20 degrees C, demonstrating the thermo-versatility of such
      organisms. Clones related to Oleispira antarctica (98% 16S rRNA similarity), a
      psychrophilic alkane degrader, were dominant in the 4 degrees C oil-degrading
      community, whereas other clones constituting a different clade and showing 94%
      similarity 16S rRNA with O. antarctica were found in situ. These findings
      demonstrate the potential for intrinsic bioremediation throughout the course of
      the year in temperate estuarine waters, and highlight the importance of both
      versatile psychrotolerant and specialized psychrophilic hydrocarbon-degrading
      microbes in effecting this process at low temperatures.

PMID- 17227423
TI  - In vitro cell growth of marine archaeal-bacterial consortia during anaerobic
      oxidation of methane with sulfate.
AB  - Anoxic sediment from a methane hydrate area (Hydrate Ridge, north-east Pacific;
      water depth 780 m) was incubated in a long-term laboratory experiment with semi
      continuous supply of pressurized [1.4 MPa (14 atm)] methane and sulfate to
      attempt in vitro propagation of the indigenous consortia of archaea (ANME-2) and
      bacteria (DSS, Desulfosarcina/Desulfococcus cluster) to which anaerobic oxidation
      of methane (AOM) with sulfate has been attributed. During 24 months of
      incubation, the rate of AOM (measured as methane-dependent sulfide formation)
      increased from 20 to 230 micromol day(-1) (g sediment dry weight)(-1) and the
      number of aggregates (determined by microscopic counts) from 0.5 x 10(8) to 5.7 x
      10(8) (g sediment dry weight)(-1). Fluorescence in situ hybridization targeting
      16S rRNA of both partners showed that the newly grown consortia contained central
      archaeal clusters and peripheral bacterial layers, both with the same morphology
      and phylogenetic affiliation as in the original sediment. The development of the
      AOM rate and the total consortia biovolume over time indicated that the consortia
      grew with a doubling time of approximately 7 months (growth rate 0.003 day(-1))
      under the given conditions. The molar growth yield of AOM was approximately 0.6 g
      cell dry weight (mol CH(4) oxidized)(-1); according to this, only 1% of the
      consumed methane is channelled into synthesis of consortia biomass.
      Concentrations of biomarker lipids previously attributed to ANME-2 archaea (e.g.
      sn-2-hydroxyarchaeol, archaeol, crocetane, pentamethylicosatriene) and
      Desulfosarcina-like bacteria [e.g. hexadecenoic-11 acid (16:1omega5c), 11,12
      methylene-hexadecanoic acid (cy17:0omega5,6)] strongly increased over time (some
      of them over-proportionally to consortia biovolume), suggesting that they are
      useful biomarkers to detect active anaerobic methanotrophic consortia in
      sediments.

PMID- 17227424
TI  - Comparison of chitinolytic enzymes from an alkaline, hypersaline lake and an
      estuary.
AB  - We examined the genetic and physiological characteristics of chitin degrading
      enzymes expressed by fosmids cloned from two strains of chitinolytic
      gammaproteobacteria isolated from alkaline, hypersaline Mono Lake, California;
      and from a metagenomic library derived from an estuarine bacterial community
      (Dean Creek, Sapelo Island, GA, USA). The Mono Lake chitinolytic enzymes
      presented unique adaptations in terms of halo- and alkalitolerance. The sequence
      from one of the Mono Lake isolates (strain 12A) was a conventional family 18
      glycosyl hydrolase; however, the expressed protein had a novel secondary activity
      peak at pH 10. We obtained a novel family 20 glycosyl hydrolase sequence from
      Mono Lake strain AI21. The activity of the expressed protein had a pH optimum of
      10, several pH units higher than any other enzyme currently assigned to this
      family, and the enzyme retained 80% of its activity at pH 11. The enzyme was also
      halotolerant, retaining activity in salt solutions of up to 225 g l(-1). Sequence
      analysis indicated a molecular weight of approximately 90 kDa for the protein,
      and that it contained two active sites. Culture supernatant contained two
      chitinolytic proteins, 45 and 31 kDa, suggesting possible post-expression
      modification of the gene product. In contrast, the sequence found in the
      estuarine metagenomic library and the functional characteristics of the protein
      expressed from it were those of a conventional family 18 glycosyl hydrolase.

PMID- 17227425
TI  - Unexpected diversity in populations of the many-celled magnetotactic prokaryote.
AB  - The many-celled magnetotactic prokaryote (MMP) is an uncultivated, highly motile
      aggregate of 10-30 cells containing numerous chains of greigite (Fe(3)S(4))
      magnetosomes. It is unique to marine environments and is abundant in slightly
      sulfidic sediments of the Little Sippewissett salt marsh (Falmouth, MA). We
      sequenced 16s rDNA genes from a natural population of MMP and found five lineages
      separated by at least 5% sequence divergence. Fluorescent in situ hybridization
      probes for three of these lineages showed significant variation in their relative
      abundances across a seasonal cycle in marsh productivity. The MMP should
      therefore be considered a separate genus in the delta-proteobacteria rather than
      a single species as previously thought. All cells in each aggregate express
      identical SSU rRNAs, suggesting that the aggregates are composed of a single MMP
      phylotype. This observation supports a model of the MMP as comprised of clonal
      cells which reproduce by binary fission of the aggregate.

PMID- 17227426
TI  - Biochemical prey recognition by planktonic protozoa.
AB  - Planktonic flagellates and ciliates are the major consumers of phytoplankton and
      bacterioplankton in aquatic environments, playing a pivotal role in carbon
      cycling and nutrient regeneration. Despite certain unicellular predators using
      chemosensory responses to locate and select their prey, the biochemical
      mechanisms behind prey reception and selection have not been elucidated. Here we
      identify a Ca(2+)-dependent, mannose-binding lectin on the marine dinoflagellate
      Oxyrrhis marina, which is used as a feeding receptor for recognizing prey.
      Blocking the receptor using 20 microM mannose-BSA inhibited ingestion of
      phytoplankton prey, Isochrysis galbana, by 60%. In prey selection studies, O.
      marina ingested twice as many 6 mum diameter beads coated with mannose-BSA as
      those coated with galNac-BSA. When pre-incubated with mannose-BSA, O. marina was
      no longer able to discriminate between different sugar-coated beads. Thus, these
      findings reveal molecular mechanisms of protozoan prey recognition. Our results
      also indicate the functional similarity between cellular recognition used by
      planktonic protozoa to discriminate between different prey items, and those used
      by metazoan phagocytic blood cells to recognize invading microorganisms.

PMID- 17227427
TI  - Identification of acetate-utilizing Bacteria and Archaea in methanogenic
      profundal sediments of Lake Kinneret (Israel) by stable isotope probing of rRNA.
AB  - Acetate is an important intermediate in the decomposition of organic matter in
      anoxic freshwater sediments. Here, we identified distinct microorganisms active
      in its oxidation and transformation to methane in the anoxic methanogenic layers
      of Lake Kinneret (Israel) profundal sediment by rRNA-based stable isotope probing
      (RNA-SIP). After 18 days of incubation with amended [U-(13)C]acetate we found
      that archaeal 16S rRNA was (13)C-labelled to a far greater extent than bacterial
      rRNA. We identified acetoclastic methanogens related to Methanosaeta concilii as
      being most active in the degradation and assimilation of acetate. Oxidation of
      the acetate-methyl group played only a minor role, but nevertheless 'heavy'(13)C
      labelled bacterial rRNA templates were identified. 'Heavy' bacteria were mainly
      affiliated with the Betaproteobacteria (mostly Rhodocyclales and
      Nitrosomonadales), the Nitrospira phylum (related to 'Magnetobacterium bavaricum'
      and Thermodesulfovibrio yellowstonii), and also with the candidate phylum
      'Endomicrobia'. However, the mode of energy gain that allowed for the
      assimilation of (13)C-acetate by these bacterial groups remains unknown. It may
      have involved syntrophic oxidation of acetate, reduction of chlorinated
      compounds, reduction of humic substances, fermentation of organic compounds, or
      even predation of (13)C-labelled Methanosaeta spp. In summary, this SIP
      experiment shows that acetate carbon was predominantly consumed by acetoclastic
      methanogens in profundal Lake Kinneret sediment, while it was also utilized by a
      small and heterogeneous community of bacteria.

PMID- 17227428
TI  - 217 000-year-old DNA sequences of green sulfur bacteria in Mediterranean
      sapropels and their implications for the reconstruction of the paleoenvironment.
AB  - Deep-sea sediments of the eastern Mediterranean harbour a series of dark, organic
      carbon-rich layers, so-called sapropels. Within these layers, the carotenoid
      isorenieratene was detected. Since it is specific for the obligately anaerobic
      phototrophic green sulfur bacteria, the presence of isorenieratene may suggest
      that extended water column anoxia occurred in the ancient Mediterranean Sea
      during periods of sapropel formation. Only three carotenoids (isorenieratene,
      beta-isorenieratene and chlorobactene) are typical for green sulfur bacteria and
      thus do not permit to differentiate between the approximately 80 known
      phylotypes. In order to reconstruct the paleoecological conditions in more
      detail, we searched for fossil 16S rRNA gene sequences of green sulfur bacteria
      employing ancient DNA methodology. 540 bp-long fossil sequences could indeed be
      amplified from up to 217 000-year-old sapropels. In addition, such sequences were
      also recovered from carbon-lean intermediate sediment layers deposited during
      times of an entirely oxic water column. Unexpectedly, however, all the recovered
      16S rRNA gene sequences grouped with freshwater or brackish, rather than truly
      marine, types of green sulfur bacteria. It is therefore feasible that the
      molecular remains of green sulfur bacteria originated from populations which
      thrived in adjacent freshwater or estuarine coastal environments rather than from
      an indigenous pelagic population.

PMID- 17227429
TI  - High viral infection rates in Antarctic and Arctic bacterioplankton.
AB  - The frequency of visibly phage-infected bacterial cells (FVIB) and the average
      number of phages per cell [i.e. burst size (BS)] were determined in Antarctic and
      Arctic ultra-oligotrophic freshwater environments. Water samples were collected
      from two Antarctic freshwater lakes and cryoconite holes from a glacier in the
      Arctic. Data from this bipolar study show the highest FVIB (average 26.1%, range
      5.1% to 66.7%) and the lowest BS (average 4, range 2-15) ever reported in the
      literature. The bacterial density is low in these ultra-oligotrophic freshwater
      environments but a large proportion of the bacteria are visibly infected. Our
      results suggest that a constant virioplankton population can be maintained in
      these extreme environments even though host density is low and often slow
      growing.

PMID- 17227430
TI  - Tn5530 from Burkholderia cepacia strain 2a encodes a chloride channel protein
      essential for the catabolism of 2,4-dichlorophenoxyacetic acid.
AB  - Chloride channel proteins (ClC) are found in living systems where they transport
      chloride ions across cell membranes. Recently, the structure/function of two
      prokaryotic ClC has been determined but little is known about the role of these
      proteins in the microbial metabolism of chlorinated compounds. Here we show that
      transposon Tn5530 from Burkholderia cepacia strain 2a encodes a ClC protein
      (BcClC) which is responsible for expelling Cl(-) ions generated during the
      catabolism of 2,4-dichlorophenoxyacetic acid (a chlorinated herbicide). We found
      that BcClC has the ability to transport Cl(-) ions across reconstituted
      proteoliposome membranes. We created two mutants in which the intrachannel
      glutamate residue of the protein, known to be responsible for opening and closing
      the channel (i.e. gating), was changed in order to create constitutively open and
      closed forms. We observed that cells carrying the closed-channel protein
      accumulated Cl(-) ions intracellularly leading to a decrease in intracellular pH,
      cell stasis and death. Further, we established that BcClC has the same gating
      mechanism as that reported for the ClC protein from Salmonella typhimurium. Our
      results show that the physiological role of ClC is to maintain cellular
      homeostasis which can be impaired by the catabolism of chlorinated compounds.

PMID- 17227431
TI  - Rapid detection and enumeration of trh-carrying Vibrio parahaemolyticus with the
      alkaline phosphatase-labelled oligonucleotide probe.
AB  - An alkaline phosphatase (AP)-labelled oligonucleotide probe was developed to
      detect and enumerate trh(+)Vibrio parahaemolyticus in seafood. The probe was
      evaluated using 40 isolates of V. parahaemolyticus, 45 isolates of other vibrios
      and 55 non-vibrio isolates. The probe reacted specifically with V.
      parahaemolyticus possessing either the trh1 or trh2 variant of the trh gene and
      was found to be 100% specific for trh(+)V. parahaemolyticus. Using the trh probe,
      V. parahaemolyticus carrying trh gene was targeted in 34 seafood samples by
      direct plating and colony hybridization procedure. The trh(+)V. parahaemolyticus
      could be detected in five of 34 (14.7%) samples and the levels ranged from 5.0 x
      10(2) to 3.4 x 10(3) cfu g(-1). Colonies of trh(+)V.parahaemolyticus were
      isolated from the five positive samples. Forty seafood samples were analysed for
      trh(+)V. parahaemolyticus by colony hybridization following enrichment in
      alkaline peptone water. 16 samples (40%) were positive for trh gene and trh(+)V.
      parahaemolyticus was isolated from 15 samples (37.5%). To assess the sensitivity
      of the trh probe, seafood homogenates spiked with known concentrations of trh
      positive V. parahaemolyticus were plated and hybridized. Counts obtained using
      the probe were similar to those of inocula. The results suggest that the AP
      labelled trh probe is useful for the detection and enumeration of trh(+)V.
      parahaemolyticus in seafood.

PMID- 17227432
TI  - Growth and mechanism of filamentous-sulfur formation by Candidatus Arcobacter
      sulfidicus in opposing oxygen-sulfide gradients.
AB  - Studies were conducted in opposing gradients of oxygen and sulfide in microslide
      capillaries to (i) characterize the chemical microenvironment preferred by
      Candidatus Arcobacter sulfidicus, a highly motile, sulfur-oxidizing bacterium
      that produces sulfur in filamentous form, and (ii) to develop a model describing
      the mechanism of filamentous-sulfur formation. The highly motile microorganisms
      are microaerophilic, with swarms effectively aggregating within oxic-anoxic
      interfaces by exhibiting a chemotactic response. The position of the band was
      found to be largely independent of the sulfide concentration as it always formed
      at the oxic-anoxic interface. Flux calculations based on steady state gradients
      of oxygen and sulfide indicate that sulfide is incompletely oxidized to sulfur,
      in line with the formation of filamentous sulfur by these organisms. It is
      proposed that Candidatus Arcobacter sulfidicus effectively competes with other
      sulfur-oxidizing bacteria in the environment by being able to tolerate higher
      concentrations of hydrogen sulfide (1-2 mM) and by possessing the ability to grow
      at very low oxygen concentrations (1-10 muM). The formation of mat-like
      structures from filamentous sulfur appears to be a population mediated effort
      allowing these organisms to effectively colonize environments characterized by
      high sulfide, low oxygen and dynamic fluid movement.

PMID- 17227434
TI  - Chronic hypoxia stress-induced differential modulation of heat-shock protein 70
      and presynaptic proteins.
AB  - Chronic hypoxia exposure can cause neurobehavioral dysfunction, but the
      underlying cellular and molecular mechanisms remain unclear. Here, we found that
      adult Lymnaea stagnalis snails maintained in low O(2) (approximately 5%) for 4
      days developed slowed reactions to light stimuli, and reduced righting movement.
      Semiquantitative immunoblotting analyses showed that hypoxia exposure induced
      increased expression of heat-shock protein (HSP)70 in ganglion preparations, and
      suppressed expression of the presynaptic proteins syntaxin I, synaptic vesicle
      protein 2 (SV2) and synaptotagmin I. Detailed time course analyses showed that an
      early moderate increase developed within 6 h, preceding a substantial up
      regulation of HSP70 after 4 days; an early reduction of syntaxin I in the first
      24 h; a delayed reduction of synaptotagmin I after 4 days; and a biphasic change
      in SV2. Using a double-stranded RNA interference approach, we demonstrated that
      preventing the hypoxia inducible HSP70 enhanced down-regulation of syntaxin and
      synaptotagmin, and aggravated motor and sensory suppression. Co
      immunoprecipitation analysis revealed an interaction between HSP70 and syntaxin.
      We have thus provided the first evidence that early induction of HSP70 by chronic
      hypoxia is critical for maintaining expression levels of presynaptic proteins.
      These findings implicate a new molecular mechanism underlying chronic hypoxia
      induced neurobehavioral adaptation and impairment.

PMID- 17227435
TI  - Differential roles of Rap1 and Rap2 small GTPases in neurite retraction and
      synapse elimination in hippocampal spiny neurons.
AB  - The Rap family of small GTPases is implicated in the mechanisms of synaptic
      plasticity, particularly synaptic depression. Here we studied the role of Rap in
      neuronal morphogenesis and synaptic transmission in cultured neurons.
      Constitutively active Rap2 expressed in hippocampal pyramidal neurons caused
      decreased length and complexity of both axonal and dendritic branches. In
      addition, Rap2 caused loss of dendritic spines and spiny synapses, and an
      increase in filopodia-like protrusions and shaft synapses. These Rap2
      morphological effects were absent in aspiny interneurons. In contrast,
      constitutively active Rap1 had no significant effect on axon or dendrite
      morphology. Dominant-negative Rap mutants increased dendrite length, indicating
      that endogenous Rap restrains dendritic outgrowth. The amplitude and frequency of
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-mediated miniature
      excitatory postsynaptic currents (mEPSCs) decreased in hippocampal neurons
      transfected with active Rap1 or Rap2, associated with reduced surface and total
      levels of AMPA receptor subunit GluR2. Finally, increasing synaptic activity with
      GABA(A) receptor antagonists counteracted Rap2's inhibitory effect on dendrite
      growth, and masked the effects of Rap1 and Rap2 on AMPA-mediated mEPSCs. Rap1 and
      Rap2 thus have overlapping but distinct actions that potentially link the
      inhibition of synaptic transmission with the retraction of axons and dendrites.

PMID- 17227436
TI  - Agmatine transport into spinal nerve terminals is modulated by polyamine analogs.
AB  - Agmatine (decarboxylated arginine) is an endogenous amine found in the CNS that
      antagonizes NMDA receptors and inhibits nitric oxide synthase. Intrathecally
      administered agmatine inhibits hyperalgesia evoked by inflammation, nerve injury
      and intrathecally administered NMDA. These actions suggest an antiglutamatergic
      neuromodulatory role for agmatine in the spinal cord. Such a function would
      require a mechanism of regulated clearance of agmatine such as neuronal or glial
      uptake. Consistent with this concept, radiolabeled agmatine has been shown to
      accumulate in synaptosomes, but the mechanism of this transport has not been
      fully characterized. The present study describes an agmatine uptake system in
      spinal synaptosomes that appears driven by a polyamine transporter.
      [(3)H]Agmatine uptake was Ca(2+), energy and temperature dependent.
      [(3)H]Agmatine transport was not moderated by L-arginine, L-glutamate, glycine,
      GABA, norepinephrine or serotonin. In contrast, [(3)H]agmatine uptake was
      concentration dependently inhibited by unlabeled putrescine and by unlabeled
      spermidine (at significantly higher concentrations). Similarly, [(3)H]putrescine
      uptake was inhibited in a concentration-dependent manner by unlabeled agmatine
      and spermidine. The polyamine analogs paraquat and methylglyoxal bis
      (guanylhydrazone) inhibited, whereas the polyamine transport enhancer
      difluoromethylornithine increased, [(3)H]agmatine transport. Taken together,
      these results suggest that agmatine transport into spinal synaptosomes may be
      governed by a polyamine transport mechanism.

PMID- 17227437
TI  - Down-regulation of dopamine transporter by iron chelation in vitro is mediated by
      altered trafficking, not synthesis.
AB  - Neurological development and functioning of dopamine (DA) neurotransmission is
      adversely affected by iron deficiency in early life. Iron-deficient rats
      demonstrate significant elevations in extracellular DA and a reduction in
      dopamine transporter (DAT) densities in the caudate putamen and nucleus
      accumbens. To explore possible mechanisms by which cellular iron concentrations
      control DAT functioning, endogenous DAT-expressing PC12 cells were used to
      determine the effect of iron chelation on DAT protein and mRNA expression
      patterns. In addition, we used human DAT (hDAT)-transfected Neuro2a (N2A) cells
      to examine DAT degradation and trafficking patterns. A 50 microM treatment for 24
      h with the iron chelator, desferrioxamine (DFO), significantly decreased dopamine
      uptake in a dose-dependent manner, with no apparent change in K(m), in both PC12
      and N2A cells. Reduced DA uptake was accompanied by concentration- and time
      dependent reductions in total DAT protein levels in both cell lines. Exposure to
      increasing concentrations of DFO did not significantly alter DAT mRNA in either
      PC12 or N2A cells. However, DAT degradation rates increased three-fivefold in
      both cell types exposed to 50 microM DFO for 24 h. Biotinylation studies in N2A
      cells indicate a more dramatic loss of DAT in the membrane fraction, while
      OptiPrep fractionation experiments revealed an increase in lysosomal DAT with
      iron chelation. Inhibition of protein kinase C activation with staurosporin
      prevented the effect of iron chelation on DAT function, suggesting that in vitro
      iron chelation affects DAT primarily through the effects on trafficking rather
      than on synthesis.

PMID- 17227438
TI  - Nicotine partially protects against paraquat-induced nigrostriatal damage in
      mice; link to alpha6beta2* nAChRs.
AB  - Epidemiological studies indicate that smoking is a negative, and exposure to
      pesticides, a positive risk factor for Parkinson's disease (PD). The purpose of
      this study was to assess the interplay between these two factors in a rodent
      model of nigrostriatal damage. To approach this, mice were administered nicotine,
      the agent in smoke implicated in neuroprotection. They were then treated for 3
      weeks with the pesticide, paraquat, while nicotine was continued. Paraquat
      treatment decreased (25%) nigral dopaminergic neurons, consistent with previous
      results. Chronic nicotine administration significantly protected against nigral
      cell damage, with only a 16% decline in mice treated with both nicotine and
      paraquat. Paraquat treatment also decreased (14%) the striatal dopamine
      transporter, an effect that was partially prevented by nicotine. These changes in
      the striatal dopamine transporter paralleled those in a select striatal
      alpha6beta2* nicotinic receptor (nAChR) subtype. In contrast, striatal
      alpha4beta2* nAChRs were not decreased with paraquat treatment, suggesting they
      are on a differential subset of dopaminergic terminals. The results show that
      nicotine treatment partially protects against paraquat-induced declines in
      nigrostriatal dopaminergic neurons to which a select population of alpha6beta2*
      nAChRs are localized. Moreover, these data support epidemiological findings that
      environmental influences can elicit opposing effects on nigrostriatal
      dopaminergic integrity.

PMID- 17227439
TI  - Adriamycin-mediated nitration of manganese superoxide dismutase in the central
      nervous system: insight into the mechanism of chemobrain.
AB  - Adriamycin (ADR), a potent anti-tumor agent, produces reactive oxygen species
      (ROS) in cardiac tissue. Treatment with ADR is dose-limited by cardiotoxicity.
      However, the effect of ADR in the other tissues, including the brain, is unclear
      because ADR does not pass the blood-brain barrier. Some cancer patients receiving
      ADR treatment develop a transient memory loss, inability to handle complex tasks
      etc., often referred to by patients as chemobrain. We previously demonstrated
      that ADR causes CNS toxicity, in part, via systemic release of cytokines and
      subsequent generation of reactive oxygen and nitrogen species (RONS) in the
      brain. Here, we demonstrate that treatment with ADR led to an increased
      circulating level of tumor necrosis factor-alpha in wild-type mice and in mice
      deficient in the inducible form of nitric oxide (iNOSKO). However, the decline in
      mitochondrial respiration and mitochondrial protein nitration after ADR treatment
      was observed only in wild-type mice, not in the iNOSKO mice. Importantly, the
      activity of a major mitochondrial antioxidant enzyme, manganese superoxide
      dismutase (MnSOD), was reduced and the protein was nitrated. Together, these
      results suggest that NO is an important mediator, coupling the effect of ADR with
      cytokine production and subsequent activation of iNOS expression. We also
      identified the mitochondrion as an important target of ADR-induced NO-mediated
      CNS injury.

PMID- 17227440
TI  - Anandamide: an update.
AB  - Endocannabinoid system has attracted the researchers to investigate into its ever
      fascinating roles governing many of the physiological functions in the human
      body. The prime endogenous cannabinoids are arachidonoylethanolamide also called
      anandamide and 2-arachidonoylglycerol. Recent pharmacological advances point out
      that this system of molecules are in initial stages and by updating our current
      knowledge, we could innovatively design molecules for suitable interventions that
      could be potentially beneficial to the mankind.

PMID- 17227441
TI  - Preclinical and clinical pharmacology of alcohol dependence.
AB  - In recent years, advances in neuroscience led to the development of new
      medications to treat alcohol dependence and especially to prevent alcohol relapse
      after detoxification. Whereas the earliest medications against alcohol dependence
      were fortuitously discovered, recently developed drugs are increasingly based on
      alcohol's neurobiological mechanisms of action. This review discusses the most
      recent developments in alcohol pharmacotherapy and emphasizes the neurobiological
      basis of anti-alcohol medications. There are currently three approved drugs for
      the treatment of alcohol dependence with quite different mechanisms of action.
      Disulfiram is an inhibitor of the enzyme aldehyde dehydrogenase and acts as an
      alcohol-deterrent drug. Naltrexone, an opiate antagonist, reduces alcohol craving
      and relapse in heavy drinking, probably via a modulation of the mesolimbic
      dopamine activity. Finally, acamprosate helps maintaining alcohol abstinence,
      probably through a normalization of the chronic alcohol-induced
      hyperglutamatergic state. In addition to these approved medications, many other
      drugs have been suggested for preventing alcohol consumption on the basis of
      preclinical studies. Some of these drugs remain promising, whereas others have
      produced disappointing results in preliminary clinical studies. These new drugs
      in the field of alcohol pharmacotherapy are also discussed, together with their
      mechanisms of action.

PMID- 17227442
TI  - Comparative effects of two type I interferons, human IFN-alpha and ovine IFN-tau
      on indoleamine-2,3-dioxygenase in primary cultures of human macrophages.
AB  - Type I interferons (IFNs) are widely used to treat viral diseases. Depressive
      symptoms and suicide attempts are common neuropsychiatric side-effects during
      treatment with type I IFNs. Activation of indoleamine-2,3-dioxygenase (IDO), the
      first and rate-limiting enzyme of the kynurenine pathway by IFNs, leads to an
      increase in tryptophan (Trp) catabolism. Low levels of Trp lead to decrease of
      serotonin synthesis, which is likely to be related to the depressive symptoms.
      Ovine type I interferon-tau (IFN-tau) has a more potent antiretroviral effect and
      is less toxic than human type I IFN-alpha. Effects of IFN-tau and IFN-alpha on
      IDO expression and activity in primary cultures of human macrophages were
      compared in parallel to those of IFN-gamma, considered as one of the most potent
      IDO inducer. We found that both IFN-alpha and IFN-tau were poor inducers of IDO
      compared with IFN-gamma. However, IDO activation was slightly and significantly
      lower with ovine IFN-tau than human IFN-alpha, suggesting that ovine IFN-tau
      might have a lower impact on serotoninergic pathway compared with human IFN
      alpha.

PMID- 17227443
TI  - Advanced-glycation end products (AGEs) derived from glycated albumin suppress
      early beta1-adrenergic preconditioning.
AB  - Ischemic heart disease in diabetic patients might be linked to the accumulation
      of advanced-glycation end products (AGEs). In ischemic rat hearts, expression of
      receptor for AGEs and its ligands is significantly enhanced and involved in
      cardiac ischemia/reperfusion (I/R) injury even in the absence of diabetes. It has
      recently been reported that diabetic human myocardium cannot be protected by
      preconditioning. In this context, our hypothesis was that beta1-adrenergic
      preconditioning might be altered in the presence of AGEs. Using an isolated non
      working rat heart model, this study investigated the effect of AGEs on
      cardioprotection induced by transient beta1-adrenoceptor (beta1-AR) stimulation
      with xamoterol (Xa). After 6-hydroxydopamine (6-OHDA) pre-treatment and a 20-min
      stabilization period, hearts were perfused at constant pressure for 20 min, then
      subjected to 40 min of global ischemia and 30 min of reperfusion (I/R, Ctrl); and
      exposed to 0.01 microm Xa for 5 min framed with or without 15.2 microm albumin
      (Alb) or glycated albumin (Gly Alb). The main endpoints were the mean coronary
      flow (MCF), the left ventricular end-diastolic pressure (LVEDP), rate-pressure
      product (RPP) and creatine kinase (CK) release and necrosis area. XA induced an
      increase in the MCF after I/R (t = 85 min), a protective effect on the LVEDP, an
      improvement in RPP, a decrease of CK release during reperfusion and a reduction
      of necrotic area. The beneficial effects induced by Xa during reperfusion were
      suppressed by the administration of Gly Alb during Xa infusion, whereas Alb did
      not hamper Xa-induced protection. These results suggest that AGEs suppress the
      cardioprotection resulting from the activation of beta1-ARs and thus might
      contribute to cardiovascular damages seen in diabetic patients.

PMID- 17227444
TI  - In vivo pharmacodynamic interactions between two drugs used in orthostatic
      hypotension--midodrine and dihydroergotamine.
AB  - A combination of midodrine and dihydroergotamine (DHE) is frequently used
      clinically in patients suffering from severe orthostatic hypotension (OH).
      Whereas midodrine acts as a selective, peripheral alpha1-receptor agonist, DHE
      displays complex pharmacology and can behave as an alpha-adrenergic receptor
      agonist or antagonist. Surprisingly, the consequences of such a combination on
      blood pressure have never been investigated. The present study was performed in
      order to evaluate the pressor effects induced by the administration of both
      midodrine and DHE in old conscious dogs (n = 6) in experimental condition
      reproducing autonomic failure-related baroreflex dysfunction (atropine 0.1
      mg/kg). For this purpose, we first studied the relative potency and intrinsic
      activity of each agonist and noradrenaline (NA) for the alpha1-adrenergic
      receptor. The orders of potency obtained in our study were 0.35, 11 and 400
      microg/kg for NA, DHE and midodrine, and intrinsic activity: NA > midodrine >
      DHE. These results strongly suggest that DHE really acts in vivo as an alpha1
      adrenoceptor partial agonist. Afterwards, the pressor effects of coadministration
      of midodrine (0.4 mg/kg) and DHE (15 microg/kg) were investigated: in one
      setting, midodrine was first administered, followed by DHE; in another, DHE was
      first administered, followed by midodrine. Our results show that in conscious
      dogs, the combination of midodrine and DHE leads to near-complete abolition of
      the pressor effect induced by the first administered drug. This in vivo proof of
      such antagonistic effects on blood pressure could explain clinical observations
      of worsening of OH in humans administered midodrine plus DHE. Although in vivo
      results obtained in conscious healthy dogs need to be experimentally and
      clinically confirmed in humans suffering from OH, these results strongly suggest
      that a midodrine-DHE combined treatment should be avoided in clinical practice.

PMID- 17227445
TI  - Contractile and relaxant properties of rat-isolated pulmonary veins related to
      localization and histology.
AB  - The aim of this study was to investigate the in vitro vasomotor properties of rat
      extra-and intralobar pulmonary veins (PVs) related to their localization and to
      assess the modulatory role of endothelium on these properties. Segments from PVs
      were mounted in small vessel myograph and stretched at various diameters (D(10),
      D(20), D(30)) corresponding to intraluminal pressures of 10, 20 or 30 mmHg. At
      D(10) or D(20), contractile responses to phenylephrine, U46619 and angiotensin II
      of distal intralobar part of PVs were smaller compared with those of proximal
      extralobar part, but no longer different when distal part was stretched at D(30).
      When submitted to an NO donor, sodium nitroprusside, distal part of PV relaxed
      more strongly when stretched at D(30) compared with D(10). Acetylcholine and
      bradykinin were devoid of relaxing effect on distal parts stretched at D(10), but
      in contrast to acetylcholine, bradykinin slightly relaxed preparations stretched
      at D(30). Isoprenaline strongly relaxed PVs ( approximately 80% of initial
      precontraction), with the distal part exhibiting a higher sensitivity to the
      agonist compared with the proximal part. This relaxation was also observed with
      salbutamol and suppressed with ICI 118551, which is in favour of the involvement
      of beta(2)-adrenoceptors in this effect. Preincubation of the preparations with
      N(G)-nitro-l-arginine methyl ester (10(-4) m) and indomethacin (10(-5) m) did not
      modify the contractile responses to U46619, nor the relaxing response to
      isoprenaline, which support that endothelium does not appear to play a
      significant modulatory role in these responses. Histological and electron
      microscopical examinations of proximal and distal sections of the same vein show
      that the layers of smooth muscle cells and cardiomyocytes were thicker in the
      proximal compared with the distal part. This study shows that, because of
      morphological heterogeneity of the PVs, the site of dissection and the initial
      condition of tension can play a significant role upon the sensitivity and the
      magnitude of the responses to both contractile and relaxing agonists.

PMID- 17227446
TI  - Intraindividual comparison of human radial and internal thoracic arteries in
      vitro and the effect of preoperative calcium blocker therapy.
AB  - The patency rate of radial artery (RA) conduits is considerably lower than that
      of internal thoracic artery (ITA) grafts and the evidence suggests that this is
      due to a clinically suspected higher incidence of vasospasm. The aim of this
      study was, therefore, to compare intraindividually the pharmacological reactivity
      of RA with that of ITA. Both RA and ITA were taken from the same patients and
      investigated in parallel. Changes in tone were monitored isometrically on ring
      preparations from both arteries in organ baths with modified Krebs-Henseleit
      solution containing 1.25 mm calcium chloride at 1 g passive preload. In
      intraindividual comparisons maximal receptor-mediated contractile responses to
      noradrenaline and endothelin-1 and endothelium-dependent acetylcholine-induced
      relaxant responses revealed no differences between both arteries. By contrast,
      depolarization-induced contractions to potassium chloride (KCl) appeared to be
      significantly higher in RA than in ITA. Further analysis, however, revealed that
      this difference was due to preoperative calcium entry blocker (Ca(2+)eB) therapy.
      Compared with control tissues, maximal responses to KCl were significantly
      attenuated in the ITA but unchanged in RA when arteries were obtained from
      patients with preoperative Ca(2+)eB therapy. The present results suggested that
      functional responses to pharmacological stimuli of both RA and ITA were quite
      similar. Preoperative Ca(2+)eB therapy, however, attenuated markedly responses to
      KCl of the ITA leaving those of RA unchanged. These results, demonstrating a
      lower sensitivity to Ca(2+)eB of RA, therefore suggested that in addition to
      Ca(2+)eB other classes of drug may be more effective at reducing the propensity
      of RA conduits to vasospasm.

PMID- 17227447
TI  - Vasorelaxant effect of iloprost on isolated human internal mammary artery.
AB  - In this study, vasodilator effect of iloprost on KCl-induced contraction in human
      internal mammary artery (IMA) was studied and compared with other vasodilators
      papaverin and diltiazem. Ring segments of IMA were studied in organ baths for
      measurement of isometric tension. After the tissues has reached their baseline
      tension, precontraction was induced by 100 mm KCl and cumulative concentration
      relaxation was measured by the application of iloprost (10(-9)-10(-6) m),
      papaverine (10(-5)-10(-4) m), diltiazem (10(-9)-10(-4) m) or ethanol; a solvent
      for iloprost; alone. The maximal relaxation of IMA segments to iloprost was 13.5
      +/- 2.2%. Iloprost caused significantly limited relaxation when compared with
      papaverin (106.0 +/- 2.9%) and diltiazem (93.6 +/- 2.5%) (P < 0.001). Papaverin
      produced the greatest maximal relaxation to KCl-induced contraction of IMA. The
      potency of iloprost (-log EC(50) = 6.59 +/- 0.19) was significantly higher than
      those of papaverine (-log EC(50) = 4.21 +/- 0.11) and diltiazem (-log EC(50) =
      5.63 +/- 0.06) (P < 0.001). In addition, -log EC(50) of diltiazem was
      significantly greater than papaverin (P < 0.001). Iloprost appears to be more
      potent than those of papaverine and diltiazem but it was inefficient in maximal
      inhibition on KCl-induced contraction. Iloprost may have little benefit in KCl
      related vasoconstriction on human IMA segments.

PMID- 17227448
TI  - Effect of alpha-asarone and a derivative on lipids, bile flow and Na+/K+-ATPase
      in ethinyl estradiol-induced cholestasis in the rat.
AB  - Administration of ethinyl estradiol (EE), a widely used component of oral
      contraceptives, has been associated with impairment of bile flow and the capacity
      to excrete organic anions in man and experimental animals. alpha-Asarone (2,4,5
      trimethoxypropenylbenzene) and 2-methoxy-4-(2-propenyl) phenoxyacetic acid (MPPA)
      have shown hypolipidemic effects. In addition to these effects, we decided to
      evaluate the properties of these compounds on EE-induced cholestasis. Wistar male
      rats were injected subcutaneously with 10 mg/kg of EE for 5 days; simultaneously,
      alpha-asarone or MPPA were also administered and appropriate controls were
      performed. alpha-asarone and MPPA decreased plasma and bile cholesterol. EE
      diminished triglycerides total, low-density lipoprotein, high-density lipoprotein
      and bile cholesterol. MPPA further decreased these lipid parameters. Alkaline
      phosphatase (an enzyme marker of cholestasis) was increased after administration
      of EE, but this effect was prevented significantly by alpha-asarone or MPPA
      administration. Bile flow was importantly decreased by EE and increased by alpha
      asarone alone. Furthermore, alpha-asarone or MPPA preserved the normal bile flow
      in EE-treated rats. EE inhibited the activity of the Na(+)/K(+)-ATPase, while
      both alpha-asarone and MPPA preserved this enzyme activity. Na(+)/K(+)-ATPase is
      involved in Na(+)-coupled uptake of bile acids into hepatocytes and, therefore,
      ultimately is the driving force for the generation of bile flow. Therefore, the
      anticholestatic effects of alpha-asarone and MPPA, described herein by the first
      time, may be due to its ability to preserve ATPase activity. This enzyme is
      negatively regulated by membrane cholesterol, thus the hypolipidemic effects of
      the compounds tested may be responsible for Na(+)/K(+)-ATPase activity and bile
      flow maintenance.

PMID- 17227449
TI  - Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a
      mouse model of diabetic neuropathic pain.
AB  - Diabetic neuropathic pain, an important microvascular complication in diabetes
      mellitus, has been recognized as one of the most difficult types of pain to
      treat. The underlying mechanisms of painful symptoms may be closely associated
      with hyperglycaemia but a lack of the understanding of its proper aetiology,
      inadequate relief, development of tolerance and potential toxicity of classical
      antinociceptives warrant the investigation of the newer agents to relieve this
      pain. The aim of the present study was to explore the antinociceptive effect of
      resveratrol on diabetic neuropathic pain and to examine its effect on serum
      tumour necrosis factor-alpha (TNF-alpha) and whole brain nitric oxide (NO)
      release. Four weeks after a single intraperitoneal injection of streptozotocin
      (STZ, 200 mg/kg), mice were tested in the tail immersion and hot-plate assays.
      Diabetic mice exhibited significant hyperalgesia along with increased plasma
      glucose and decreased body weights when compared with control mice. Daily
      treatment with resveratrol (5, 10 and 20 mg/kg body weight; p.o.) for 4 weeks
      starting from the 4th week of STZ injection significantly attenuated thermal
      hyperalgesia. Resveratrol also decreased the serum TNF-alpha levels and whole
      brain NO release in a dose-dependent manner. These results point towards the
      potential of resveratrol in attenuating diabetic neuropathic pain.

PMID- 17227450
TI  - The effect of modulation of gamma-glutamyl transpeptidase and nitric oxide
      synthase activity on GSH homeostasis in HepG2 cells.
AB  - High glutathione (GSH) level and elevated gamma-glutamyl transpeptidase (gammaGT)
      activity are hallmarks of tumor cells. Toxicity of drugs and radiation to the
      cells is largely dependent on the level of thiols. In the present studies, we
      attempted to inhibit gammaGT activity in human hepatoblastoma (HepG2) cells to
      examine whether the administration of gammaGT inhibitors, acivicin (AC) and
      1,2,3,4-tetrahydroisoquinoline (TIQ) influences cell proliferation and enhances
      cytostatic action of doxorubicin (DOX) and cisplatin (CP) on HepG2 cells. The
      effects of these inhibitors were determined by 1-(4,5-dimethylthiazol-2-yl)-3,5
      diphenylformazan (MTT), BrdU and lactate dehydrogenase (LDH) tests and by
      estimation of GSH level. Additionally, we investigated the changes in caspase-3
      activity, which is a marker of apoptosis. The obtained results showed that the
      gammaGT inhibitors introduced to the medium alone elicited cytotoxic effect,
      which was accompanied by an increase in GSH level in the cells. TIQ concomitantly
      increased caspase-3 activity. Doxorubicin and CP proved to be cytotoxic, and both
      inhibitors augmented this effect. As well DOX as CP radically decreased GSH
      levels, whereas gammaGT inhibitors had diverse effects. Therefore, the obtained
      results confirm that gammaGT inhibitors can enhance pharmacological action of DOX
      and CP, which may permit clinicians to decrease their doses thereby alleviating
      side effects. Aminoguanidine (nitric oxide synthase inhibitor) given alone was
      little cytotoxic to HepG2 cells, while its introduction to the medium together
      with DOX and CP significantly increased their cytotoxicity. Aminoguanidine on its
      own did not show any effect on GSH level in HepG2 cells, but markedly and
      significantly elevated its concentration when added in combination with CP but
      not with DOX. This indicates that when CP was used as a cytostatic, GSH level
      rose after treatment with its combination with both AC and aminoguanidine.

PMID- 17227451
TI  - MnTBAP, a synthetic metalloporphyrin, inhibits production of tumor necrosis
      factor-alpha in lipopolysaccharide-stimulated RAW 264.7 macrophages cells via
      inhibiting oxidative stress-mediating p38 and SAPK/JNK signaling.
AB  - Antioxidants are able to inhibit inflammatory gene expression in response to
      lipopolysaccharide via down-regulating generation of intracellular reactive
      oxygen species (ROS) as second messengers. The effect of manganese (III) tetrakis
      (4-benzoic acid) porphyrin (MnTBAP), a synthetic metalloporphyrin with
      antioxidant activity, on tumor necrosis factor (TNF)-alpha production in
      lipopolysaccharide-stimulated RAW 264.7 macrophage cells was examined. MnTBAP
      prevented the generation of intracellular ROS in lipopolysaccharide-stimulated
      RAW 264.7 cells and further inhibited lipopolysaccharide-induced TNF-alpha
      production. MnTBAP exclusively prevented the phosphorylation of p38 mitogen
      activated protein kinase (MAPK) and stress-activated protein kinase (SAPK/JNK)
      whereas it did not affect the phosphorylation and activation of nuclear factor
      kappaB and extracellular signal regulated kinase 1/2. MnTBAP was suggested to
      inhibit lipopolysaccharide-induced TNF-alpha production by the prevention of
      intracellular ROS generation and subsequent inactivation of p38 MAPK and
      SAPK/JNK.

PMID- 17227452
TI  - Possible involvement of ActVI-ORFA in transcriptional regulation of actVI
      tailoring-step genes for actinorhodin biosynthesis.
AB  - The actinorhodin biosynthetic gene (act) cluster in Streptomyces coelicolor
      carries a functionally unknown gene, actVI-ORFA. We have characterized an ActVI
      ORFA disruptant by functional complementation and reverse transcriptase
      polymerase chain reaction analysis of the expression profiles of the act genes.
      Introduction of the functional actVI-ORFA gene into the disruptant restored
      actinorhodin production to an extent similar to that seen in the wild-type cells
      and abolished the accumulation of actinorhodin biosynthetic intermediates and
      shunt products specific for actVI mutants. Thus, unique phenotypes observed in
      the mutant are solely dependent on the function of actVI-ORFA. The disruptant was
      shown to yield significantly lower levels of the transcripts for certain act
      genes, especially for the actVI-ORF1-VA-ORF2 transcription unit, leading to the
      accumulation of the intermediates and shunt products. The functional actVI-ORFA
      gene restored expression of actVI-ORF1, which encodes a key reductase in the
      actinorhodin tailoring step, in the mutant cells, indicating a possible
      regulatory role of ActVI-ORFA.

PMID- 17227453
TI  - Dimeric structure of nucleoside diphosphate kinase from moderately halophilic
      bacterium: contrast to the tetrameric Pseudomonas counterpart.
AB  - Light scattering and chemical cross-linking analyses of nucleoside diphosphate
      kinase (NDK) from moderate halophile, Halomonas sp. 593 (HaNDK), unambiguously
      demonstrated that this enzyme formed a dimeric structure, in contrast to the
      Pseudomonas NDK (PaNDK), a nonhalophilic counterpart, and other NDKs from Gram
      negative bacteria, which all formed a tetrameric structure. Comparison of HaNDK
      and PaNDK showed that the HaNDK was less thermally stable than the PaNDK: the
      optimum temperature of PaNDK enzyme activity was 20 degrees C higher than that of
      HaNDK. However, the HaNDK readily refolded and reassembled back to the active
      dimeric structure, upon heat denaturation at 0.2 M NaCl, as soon as the
      temperature was lowered. On the contrary, the thermally more stable PaNDK was
      irreversibly denatured at its melting temperature.

PMID- 17227454
TI  - Alcohol increases hemolysis by staphylococci.
AB  - It was recently found that alcohols can confer hemolytic properties on certain
      species of yeast. Here, it is reported that alcohol can promote hemolysis by
      various species of staphylococci, including strains of Staphylococcus aureus,
      Staphylococcus epidermidis and Staphylococcus hominis. In order to study this
      novel phenomenon in S. aureus and S. epidermidis, strains that exhibit this
      phenomenon (e.g. S. aureus 8325-4, COL, SH1000, S. epidermidis), as compared with
      strains that exhibited little alcohol-enhanced hemolysis (e.g. S. aureus 8325-4
      DeltaTRAP, RN6911) were examined. Both ethanol and n-butanol caused upregulation
      of the virulence regulator-RNAIII, with a concomitant increase in the production
      of alpha, beta and gamma-hemolysins in strain 8325-4. In S. aureus COL and
      SH1000, there was an increase in RNAIII but no change in transcription levels of
      alpha, beta and gamma hemolysins. Staphylococcus epidermidis stain sofi exhibited
      increased RNAIII and beta hemolysin production. Staphylococcus aureus mutant
      strains (8325-4 DeltaTRAP and RN6911) showed no change in the transcription level
      of the RNAIII regulator and the above hemolysins. Increased hemolysis in S.
      aureus COL, SH1000 and mutant strains may be caused by other hemolysins (not
      regulated by RNAIII) or through other mechanisms such as hyperoxidation or
      cytotoxic lipids.

PMID- 17227455
TI  - Oryza sativa rice plants contain molecules that activate different quorum-sensing
      N-acyl homoserine lactone biosensors and are sensitive to the specific AiiA
      lactonase.
AB  - Gram-negative bacteria most often use N-acyl homoserine lactones (AHLs) as
      intercellular quorum-sensing signal molecules. In this study, it was demonstrated
      that rice plants contain AHL mimic molecules that are very sensitive to the
      highly specific AiiA lactonase enzyme and can activate three different AHL
      bacterial biosensors, indicating that the compounds have a homoserine lactone
      structure and could be AHLs. The possible source and biological significance of
      this finding are discussed.

PMID- 17227456
TI  - A new Sodalis lineage from bloodsucking fly Craterina melbae (Diptera,
      Hippoboscoidea) originated independently of the tsetse flies symbiont Sodalis
      glossinidius.
AB  - Symbiotic bacterium closely related to the secondary symbiont of tsetse flies,
      Sodalis glossinidius, has been described from the bloodsucking fly Craterina
      melbae. Phylogenetic analysis of two genes, 16S rRNA gene and component of type
      three secretion system, placed the bacterium closer to the Sitophilus-derived
      branch of Sodalis than to the tsetse symbionts. This indicates that the Craterina
      derived lineage of Sodalis originated independent of the tsetse flies symbionts
      and documents the capability of Sodalis bacteria either to switch between
      different host groups or to establish the symbiosis by several independent
      events.

PMID- 17227457
TI  - Selenite-reducing capacity of the copper-containing nitrite reductase of
      Rhizobium sullae.
AB  - Rhizobium sullae strain HCNT1 contains a nitric oxide-producing nitrite reductase
      of unknown function due to the absence of a complementary nitric oxide reductase.
      HCNT1 had the ability to grow on selenite concentrations as high as 50 mM, and
      during growth, selenite was reduced to the less toxic elemental selenium. An
      HCNT1 mutant lacking nitrite reductase grew poorly in the presence of 5 mM
      selenite, was unable to grow in the presence of 25 or 50 mM selenite and also
      showed no evidence of selenite reduction. A naturally occurring nitrite reductase
      deficient R. sullae strain, CC1335, also showed little growth on the higher
      concentrations of selenite. Mobilization of a plasmid containing the HCNT1 gene
      encoding nitrite reductase into CC1335 increased its resistance to selenite. To
      confirm that this ability to grow in the presence of high concentrations of
      selenite correlated with nitrite reductase activity, a new nitrite reductase
      containing strain was isolated from the same location where HCNT1 was isolated.
      This strain was also resistant to high concentrations of selenite. Inactivation
      of the gene encoding nitrite reductase in this strain increased selenite
      sensitivity. These data suggest that the nitrite reductase of R. sullae provides
      resistance to selenite and offers an explanation for the radically truncated
      denitrification found uniquely in this bacterium.

PMID- 17227458
TI  - Characterization and molecular cloning of a heterodimeric beta-galactosidase from
      the probiotic strain Lactobacillus acidophilus R22.
AB  - Beta-galactosidase from the probiotic strain Lactobacillus acidophilus R22 was
      purified to apparent homogeneity by ammonium sulphate fractionation, hydrophobic
      interaction, and affinity chromatography. The enzyme is a heterodimer consisting
      of two subunits of 35 and 72 kDa, as determined by gel electrophoresis. The
      optimum temperature of beta-galactosidase activity was 55 degrees C (10-min
      assay) and the range of pH 6.5-8, respectively, for both o-nitrophenyl-beta-D
      galactopyranoside (oNPG) and lactose hydrolysis. The Km and Vmax values for
      lactose and oNPG were 4.04+/-0.26 mM, 28.8+/-0.2 micromol D-glucose released per
      min per mg protein, and 0.73+/-0.07 mM, 361+/-12 micromol o-nitrophenol released
      per min per mg protein, respectively. The enzyme was inhibited by high
      concentrations of oNPG with Ki,s=31.7+/-3.5 mM. The enzyme showed no specific
      requirements for metal ions, with the exception of Mg2+, which enhanced both
      activity and stability. The genes encoding this heterodimeric enzyme, lacL and
      lacM, were cloned, and compared with other beta-galactosidases from lactobacilli.
      Beta-galactosidase from L. acidophilus was used for the synthesis of prebiotic
      galacto-oligosaccharides (GOS) from lactose, with the maximum GOS yield of 38.5%
      of total sugars at about 75% lactose conversion.

PMID- 17227459
TI  - Type III secretion system-associated pilus of Pseudomonas syringae as an epitope
      display tool.
AB  - Type III secretion system-associated pili found in several plant pathogenic
      bacteria are required for injection of virulence proteins from bacteria into the
      plant cells. The possibility to use the type III secretion pilus of Pseudomonas
      syringae as an epitope display tool was studied. The advantage of the type III
      secretion pilus, compared with conventional fimbrial epitope display tools, is
      that the pilin subunits of the type III secretion pilus can auto-assemble into
      intact pili in vitro. Various peptides were inserted into the type III secretion
      pilin subunit, and secretion, assembly and surface properties of the modified
      pili were monitored. It was concluded that the outwards-projecting N-terminal
      region of the pilin can bear even 43 amino acids insertion. The three-dimensional
      structure of the epitope, however, can restrict the use of the pilus as an
      epitope display tool: a beta-hairpin structure was poorly tolerated.

PMID- 17227460
TI  - Differential expression of cysteine proteases in developmental stages of the
      parasitic ciliate Ichthyophthirius multifiliis.
AB  - An expressed sequence tag database of the freshwater fish parasite,
      Ichthyophthirius multifiliis (Ciliophora) was analyzed to seek for proteases
      potentially involved in the invasion and degradation of host tissues during
      infection. The translation of the database revealed two cathepsin L cysteine
      proteases (Icp1 and Icp2) of the C1A peptidase subfamily. The analysis of Icp1
      and Icp2 sequences suggested that both proteases would be synthesized as
      preproproteins, with a mature domain of 27.9 and 22.8 kDa, respectively. Their
      expression level was determined in the trophont parasitic stage, in the tomont
      reproductive stage, and in the theront infective stage by real-time RT-PCR. ICP1
      and ICP2 were significantly upregulated in trophont and theront stages in
      comparison with the tomont stage. Mature peptides of Icp1 and Icp2 were
      identified in crude extracts of I. multifiliis trophonts by LC-MS/MS. Zymograms
      showed three to seven activity bands at the optimum pH of cathepsin L cysteine
      proteases. Two bands displaying cysteine protease activity were identified by
      inhibition with E-64. They represented the major proteolytic activity of the
      trophont stage at pH 5-7, suggesting that cysteine proteases play an important
      role in the infection process.

PMID- 17227461
TI  - A comprehensive survey on isoleucine biosynthesis pathways in seven epidemic
      Leptospira interrogans reference strains of China.
AB  - Previous studies have indicated that different species of Leptospira synthesize
      isoleucine via either pyruvate and/or threonine pathways. Seven epidemic
      Leptospira interrogans reference strains from China belonging to different
      serovars, together with three saprophytic strains of Leptospira biflexa and
      Leptospira meyeri, were analysed. The isoleucine biosynthesis properties were
      studied firstly by measuring the key enzymes of the two pathways, citramalate
      synthase (CimA, CE4.1.3.-) and threonine deaminase (IlvA, CE4.2.1.16), from cell
      extracts of the bacteria. Meanwhile, alpha-isopropylmalate synthase (LeuA,
      CE4.2.1.12), the key enzyme of leucine biosynthesis, was also measured as a
      control. It was found that all L. interrogans strains synthesized isoleucine via
      the pyruvate pathway exclusively, but L. biflexa and L. meyeri used both
      pathways. Dot-Blot and PCR amplification of both cimA and ilvA genes in the
      corresponding strains provided additional evidence consistent with the data of
      enzymatic assays. Although it is evident that leptospires' isoleucine
      biosynthesis may preferentially adapt either to the pyruvate pathway exclusively
      for pathogens or to the combination of both pyruvate and threonine pathways for
      saprophytes, broader sampling with careful genomospecies identification is needed
      for a solid conclusion.

PMID- 17227463
TI  - Activation of quiescent infections by postharvest pathogens during transition
      from the biotrophic to the necrotrophic stage.
AB  - Insidious fungal infections of postharvest pathogens remain quiescent, as
      biotrophs, during fruit growth and harvest, but activate their development and
      transform to necrotrophs, which elicit decay symptoms, during ripening and
      senescence. Exposure of unripe hosts to pathogens quickly initiates defensive
      signal-transduction cascades that limit fungal growth and development, but
      exposure to the same pathogens during ripening and storage activates a
      substantially different signaling cascade that facilitates fungal colonization.
      The first step in the activation of quiescent infections may involve the fungal
      capability to cope with plant defense responses by detoxification and efflux
      transport of antifungals, or by overcoming the suppression of pathogenicity
      factors. The second step toward the activation of quiescent infections is
      actively modulated by the pathogen in response to a host signal(s), and includes
      alkalization or ammonification of the host tissue, which sensitizes the host and
      activates the transcription and secretion of fungal-degradative enzymes that
      promote maceration of the host tissue. Feedback signals involving, for example,
      nitrogen and sugar further enhance pH changes, synthesis of hydrolytic enzymes
      and saprophytic development in the macerated tissue. This review describes the
      coordinated series of mechanisms that regulate the activation of quiescent
      infections in various fruit/vegetable-pathogen interactions.

PMID- 17227462
TI  - RNA-mediated gene silencing in the phytopathogenic fungus Bipolaris oryzae.
AB  - The Ascomycetous fungus Bipolaris oryzae is the causal agent of brown leaf spot
      disease in rice and is a model for studying photomorphogenetic responses by near
      UV radiation. Targeted gene disruption (knockout) for functional analysis of
      photomorphogenesis-related genes in B. oryzae can be achieved by homologous
      recombination with low efficiency. Here, the applicability of RNA silencing
      (knockdown) as a tool for targeting endogenous genes in B. oryzae is reported. A
      polyketide synthase gene (PKS1), involved in fungal DHN melanin biosynthesis
      pathways, was targeted by gene silencing as a marker. The silencing vector
      encoding hairpin RNA of the PKS1 fragment was constructed in a two-step PCR-based
      cloning, and introduced into the B. oryzae genomic DNA. Silencing of the PKS1
      gene resulted in albino phenotypes and reduction of PKS1 mRNA expression. These
      results demonstrate the applicability of targeted gene silencing as a useful
      reverse-genetics approach in B. oryzae.

PMID- 17227464
TI  - Biogenic volatile organic compounds as potential carbon sources for microbial
      communities in soil from the rhizosphere of Populus tremula.
AB  - Catabolism of a (14)C-labelled volatile monoterpene compound (geraniol) to
      (14)CO(2) was investigated in soils taken from the rhizosphere at distances up to
      200 cm from the trunks of three small Populus tremula trees growing at different
      sites in Slovenia. Emissions of limonene of up to 18 microg m(-2) h(-1) were
      detected from the soil surface at each site. Evolution of (14)C-labelled CO(2)
      was measured as a product of catabolism of (14)C-labelled geraniol introduced
      into the soil samples. Indigenous soil microorganisms degraded the geraniol
      rapidly. There was a significant difference in relative lag times and rates of
      catabolism along the gradient from the tree trunks, with relatively longer lag
      times and lower rates occurring in soil samples from the farthest point from the
      tree.

PMID- 17227465
TI  - Speciation of sulfur from filamentous microbial mats from sulfidic cave springs
      using X-ray absorption near-edge spectroscopy.
AB  - Most transformations within the sulfur cycle are controlled by the biosphere, and
      deciphering the abiotic and biotic nature and turnover of sulfur is critical to
      understand the geochemical and ecological changes that have occurred throughout
      the Earth's history. Here, synchrotron radiation-based sulfur K-edge X-ray
      absorption near-edge structure (XANES) spectroscopy is used to examine sulfur
      speciation in natural microbial mats from two aphotic (cave) settings. Habitat
      geochemistry, microbial community compositions, and sulfur isotope systematics
      were also evaluated. Microorganisms associated with sulfur metabolism dominated
      the mats, including members of the Epsilonproteobacteria and Gammaproteobacteria.
      These groups have not been examined previously by sulfur K-edge XANES. All of the
      mats consisted of elemental sulfur, with greater contributions of cyclo
      octasulfur (S8) compared with polymeric sulfur (Smicro). While this could be a
      biological fingerprint for some bacteria, the signature may also indicate
      preferential oxidation of Smicro and S8 accumulation. Higher sulfate content
      correlated to less S8 in the presence of Epsilonproteobacteria. Sulfur isotope
      compositions confirmed that sulfur content and sulfur speciation may not
      correlate to microbial metabolic processes in natural samples, thereby
      complicating the interpretation of modern and ancient sulfur records.

PMID- 17227466
TI  - Proteomics analysis of the Francisella tularensis LVS response to iron
      restriction: induction of the F. tularensis pathogenicity island proteins IglABC.
AB  - Francisella tularensis is a highly virulent, facultative intracellular pathogen
      that causes tularemia in humans and animals. Although it is one of the most
      infectious bacterial pathogens, little is known about its virulence mechanisms.
      In this study, the response of F. tularensis live vaccine strain to iron
      depletion, which simulates the environment within the host, was investigated. In
      order to detect alterations in protein synthesis, metabolic labeling, followed by
      2D-PAGE analysis was used. Globally, 141 protein spots were detected whose levels
      were significantly altered in the iron-restricted medium. About 65% of the spots
      were successfully identified using mass spectrometric approaches. Importantly,
      among the proteins produced at an increased level during iron-limited growth,
      three proteins were found encoded by the igl operon, located in the F. tularensis
      pathogenicity island I (FPI). Of these, the IglC and IglA proteins were
      previously reported to be necessary for full virulence of F. tularensis. These
      results, obtained at the proteome level, support and confirm recently published
      data showing that the igl operon genes are transcribed in response to iron
      limitation.

PMID- 17227467
TI  - Rhizobitoxine production in Agrobacterium tumefaciens C58 by Bradyrhizobium
      elkanii rtxACDEFG genes.
AB  - We examined the genetic basis and transfer for production of rhizobitoxine, an
      inhibitor of ethylene biosynthesis in plants, directed by the rtx genes of
      Bradyrhizobium elkanii. Comparison with genome sequences of Bradyrhizobium
      japonicum and Xanthomonas oryzae suggests that the rtx genes extend from the
      previously identified rtxAC genes through four additional genes rtxDEFG. Reverse
      transcription-PCR analysis showed that the rtxACDEFG genes are expressed as an
      operon. Mutational analysis indicated that rtxDEG mutants reduced rhizobitoxine
      biosynthesis, while the rtxA gene is essential for its synthesis. Introduction of
      the rtxACDEFG into Agrobacterium tumefaciens resulted in strong expression of
      rtxACDEFG and production of RtxA protein, but no rhizobitoxine was detectable.
      Addition of O-acetylhomoserine, a precursor of rhizobitoxine, to the
      Agrobacterium derivative, however, fostered production of rhizobitoxine in
      culture. The diluted culture supernatant inhibited the activities of beta
      cystathionase and 1-aminocyclopropane-1-carboxylate synthase, indicating that A.
      tumefaciens carrying rtxACDEFG genes excreted biologically active rhizobitoxine.

PMID- 17227468
TI  - Transcription in Escherichia coli PHL628 biofilms.
AB  - The biofilm-specific gene expression of Escherichia coli PHL628 was compared with
      that from exponentially growing planktonic cells using macroarray technology. In
      duplicate experiments, both biofilm and planktonic cells were grown in separate
      continually stirred tank reactors at 57% of the maximal planktonic growth rate.
      When transcriptional results from planktonic cultures were compared with that of
      biofilm grown cells, c. 4.5% of the genome showed a significant change in
      expression. The results presented here point to an extremely heterogeneous
      biofilm wherein specific gene induction was consistent with the response of
      biofilm cells to gradients in electron acceptors, nutrients, carbon source and a
      variety of stresses. A mutant in one of the genes, gspM (pshM), that was induced
      in biofilms was constructed and was shown to be compromised for its ability to
      form mature biofilms. This analysis provides additional insight into the genes
      induced during biofilm development, the gradients they respond to, the
      contribution of one gene to biofilm development, and a comparison of this with
      other transcriptional profiles from E. coli biofilms.

PMID- 17227469
TI  - Two noncellulosomal cellulases of Clostridium thermocellum, Cel9I and Cel48Y,
      hydrolyse crystalline cellulose synergistically.
AB  - The genome of Clostridium thermocellum contains a number of genes for
      polysaccharide degradation-associated proteins that are not cellulosome bound.
      The list includes beta-glucanases, glycosidases, chitinases, amylases and a
      xylanase. One of these 'soluble'-enzyme genes codes for a second glycosyl
      hydrolase (GH)48 cellulase, Cel48Y, which was expressed in Escherichia coli and
      biochemically characterized. It is a cellobiohydrolyse with activity on native
      cellulose such as microcrystalline and bacterial cellulose, and low activity on
      carboxymethylcellulose. It is about 100 times as active on amorphic cellulose and
      mixed-linkage barley beta-glucan compared with cellulase Cel9I. The enzyme Cel48Y
      shows a distinct synergism of 2.1 times with the noncellulosomal processive
      endoglucanase Cel9I on highly crystalline bacterial cellulose at a 17-fold excess
      of Cel48Y over Cel9I. These data show that C. thermocellum has, besides the
      cellulosome, the genes for a second cellulase system for the hydrolysis of
      crystalline cellulose that is not particle bound.

PMID- 17227470
TI  - The intracellular proteolytic system of Yarrowia lipolytica and characterization
      of an aminopeptidase.
AB  - Intracellular proteases of Yarrowia lipolytica have been scarcely studied. These
      enzymes may play an important role in nitrogen metabolism, posttranslational
      processing, nutritional stress, dimorphism, etc.; biochemical and genetic control
      of these enzymes can help in obtaining high-level expression of recombinant
      proteins in heterologous systems. In this study, we report the presence of three
      proteases: aminopeptidase yylAPE, carboxypeptidase yylCP and dipeptidyl
      aminopeptidase yylDAP, measured under several nutritional conditions. Yarrowia
      lipolytica produced the highest level of intracellular proteolytic enzymes, i.e.
      yylAPE, yylCP and yylDAP, in media with peptone during stationary growth phase.
      When soluble extracts were subjected to PAGE, and the three activities were
      revealed in gels with the corresponding substrates, only one band of activity was
      detected for each one. The three enzymes were affected by serine protease
      inhibitors. Chelating agents affected mainly APE activity. The aminopeptidase was
      purified by selective fractionation with ammonium sulfate and three
      chromatographic steps (anion exchange, hydrophobic interaction and gel filtration
      chromatography). The enzyme had a molecular mass of 97 kDa; optimal pH and
      temperature were 7.0 and 37 degrees C, respectively. The aminopeptidase showed a
      preference for lysine in the N-position. The K(m) value was 0.86 microM and
      V(max) value was 990.8 micromoL min(-1) mg(-1) for Lys-pNA.

PMID- 17227471
TI  - Bacillus subtilis rapD, a direct target of transcription repression by RghR,
      negatively regulates srfA expression.
AB  - The Bacillus subtilis genome encodes eleven Rap proteins, which are conserved
      tetratricopeptide-containing regulatory proteins. Of those characterized to date,
      all except RapI negatively regulate response regulators, including Spo0F, ComA
      and DegU, via protein-protein interactions. RapD has not yet been fully
      characterized. It was examined whether RapD inhibits the expression of spoIIE,
      srfA and aprE, which are Spo0F-, ComA- and DegU-regulated genes, respectively. It
      was observed that multicopy rapD inhibited srfA expression, which suggests that
      RapD inhibits ComA. This was reinforced by the fact that multicopy rapD also
      blocked the expression of rapC and rapF, which belong to the ComA regulon. The
      expression of rapD was reported to depend on the extracytoplasmic function sigma
      factor SigX. DNA microarray analysis and gel retardation assays revealed that
      rapD expression is directly repressed by RghR. Thus, the ComA regulon is
      regulated by rapD in a SigX- and RghR-dependent manner.

PMID- 17227472
TI  - The impact of ACE genotype on serum ACE activity in a black South African male
      population.
AB  - The strong association between the angiotensin I-converting enzyme (ACE) gene I/D
      polymorphism with serum ACE activity appears lacking in Nigerians and Kenyans,
      but has not previously been well assessed in others of African origin. This study
      addressed this issue in an ethnically well defined black South African
      population. A putative association for the A22982G ACE gene variant, a QTL likely
      to impact on serum ACE activity, was also sought. Subjects were 200 healthy male
      black South African volunteers from the Xhosa ethnic group. Venous blood was
      obtained from all subjects for DNA extraction. ACE I/D and A22982G genotypes were
      determined and serum ACE activity measured. Age and blood pressure were recorded.
      For the group as a whole (mean +/- SD age 38.5 +/- 9.8 years, SBP 119.6 +/- 14.1
      mmHg, DBP 78.2 +/- 10.1 mmHg) serum ACE activity was 38.2 +/- 11.2 nmol ml(
      1)min(-1). ACE I/D genotype was not significantly associated with serum ACE
      activity. In contrast, the A22982G variant was significantly associated with
      serum ACE activity, being 35.9 +/- 9.6, 38.1 +/- 10.6 and 42.4 +/- 15.3 nmol ml(
      1)min(-1) for AA, AG and GG genotypes respectively; p = 0.03 by ANOVA and p =
      0.01 by linear trend. In keeping with the findings in some other African
      populations, the ACE I/D polymorphism is not strongly associated with serum ACE
      activity in Xhosa South Africans. As such, it cannot be used as a marker of ACE
      activity in these subjects. In this regard the use of the A22982G gene variant
      may be more appropriate.

PMID- 17227473
TI  - Non-SCN5A related Brugada syndromes: verification of normal splicing and
      trafficking of SCN5A without exonic mutations.
AB  - Recently, it has been reported that under 20% of Brugada syndrome cases are
      linked to SCN5A mutations. The purpose of this study was to clarify whether
      abnormalities other than exonic mutations, such as splicing disorders, decreased
      mRNA expression levels, or membrane transport abnormalities of SCN5A, play a role
      in the pathogenesis of Brugada syndrome. We analyzed all SCN5A exons and splice
      sites using genomic DNA from 23 Brugada syndrome patients. We also analyzed the
      mRNA obtained from RV cardiomyocytes using real time PCR and sequencing, to study
      the expression levels and splicing patterns of SCN5A. The localization of SCN5A
      was examined by immunofluorescence analysis. A de novo heterozygous G to A
      transversion in a 5' splice junction of the intron between exons 21 and 22 was
      detected in 1 patient. In the mRNA analysis of Brugada syndrome patients without
      a mutation of SCN5A no splicing abnormalities were detected, and the SCN5A mRNA
      levels were similar to those of normal controls. Immunofluorescence analyses
      revealed that SCN5A is located on the surface membrane not only in the RV
      cardiomyocytes of normal controls but also in those with Brugada syndrome. We can
      confirm that some Brugada syndrome patients without exonic mutations in SCN5A had
      no other SCN5A abnormalities, including any involving the location of the SCN5A
      protein. These results suggest the involvement of other proteins in the
      pathogenesis in Brugada syndrome.

PMID- 17227475
TI  - Complex segregation analysis accounting for GxE of bone mineral density in
      European pedigrees selected through a male proband with low BMD.
AB  - Osteoporosis is a common multifactorial disorder characterized by low bone mass
      (BMD) and high susceptibility to low-trauma fractures. Family and twin studies
      have found a strong genetic component in the determination of BMD, but the mode
      of inheritance of this trait is not yet fully understood. BMD is a complex trait
      whose expression is confounded by environmental influences and polygenic
      inheritance. Detection of potential gene-environment interactions is of great
      interest in the determination of bone health status. Here we have conducted
      segregation analyses, using the regressive class D models, in a sample of 100
      European pedigrees (NEMO) with 713 subjects (524 measured for phenotypes)
      identified via a male with low BMD values at either the Lumbar Spine or the
      Femoral Neck. Segregation analyses were conducted on the residuals of LS-BMD and
      FN-BMD adjusted for gender, age and BMI. We tested for gene-covariate (GxE)
      interactions, and investigated the impact of significant GxE interactions on
      segregation results. Without GxE a major effect was found to be marginally
      significant in LS-BMD and highly significant in FN-BMD. For both traits the
      Mendelian hypothesis was rejected. Significant Age x gene and BMI x gene
      interactions were revealed. Accounting for GxE increased statistical evidence for
      a major factor in LS-BMD, and improved the fit of the data to the Mendelian
      transmission model for both traits. The best fitting models suggested a
      codominant major gene accounting for 45% (LS-BMD) and 44% (FN-BMD) of the
      adjusted BMDs. However, substantial residual correlations were also found, and
      these remained highly significant after accounting for the major gene.

PMID- 17227474
TI  - Haplotype structure of FSHB, the beta-subunit gene for fertility-associated
      follicle-stimulating hormone: possible influence of balancing selection.
AB  - Follicle-stimulating hormone (FSH) is essential for human reproduction. The
      unique functions of this hormone are provided by the FSH receptor-binding beta
      subunit encoded by the FSHB gene. Resequencing and genotyping of FSHB in three
      European, two Asian and one African population, as well as in the great apes
      (chimpanzee, gorilla, orangutan), revealed low diversity and significant excess
      of polymorphisms with intermediate frequency alleles. Statistical tests for FSHB
      showed deviations from neutrality in all populations suggesting a possible effect
      of balancing selection. Two core haplotypes were identified (carried by 76-96.6%
      of each population's sample), the sequences of which are clearly separated from
      each other. As fertility most directly affects an organism's fitness, the
      carriers of these haplotypes have apparently had more success in human history to
      contribute to the next generation. There is a preliminary observation suggesting
      that the second most frequent FSHB haplotype may be associated with rapid
      conception success in females. Interestingly, the same haplotype is related to an
      ancestral FSHB variant shared with the ancestor of the great apes. The
      determination of the functional consequence of the two core FSHB variants may
      have implications for understanding and regulating human fertility, as well as in
      assisting infertility treatments.

PMID- 17227476
TI  - Heritability for plasma VEGF concentration in the Stanislas family study.
AB  - Vascular endothelial growth factor (VEGF), a key regulator of blood vessel
      function during angiogenesis, has been related to various diseases including
      atherosclerosis, neurodegenerative disorders and cancers. However, data about
      genetic determinants of its concentration in blood are scarce. The present study
      aimed at estimating additive genetic heritability, household component effect and
      the influence of 3 common VEGF polymorphisms on plasma VEGF concentration. A
      random sub-sample of 160 nuclear families (647 individuals), aging from 5 to 57,
      was obtained from the Stanislas Family Study. Plasma VEGF concentration was
      measured by a multiplexing ELISA and genotyping of the polymorphisms C(-460)T,
      G(405)C and C(936)T of the VEGF gene was carried out by RFLP. After adjustment
      for the influence of known environmental covariates, significant familial
      correlations were observed for plasma VEGF concentration (P< or = 0.01 and P< or
      = 0.001) for all the various pairs of relatives, except between spouses. In
      addition, variance component analysis showed no significant household common
      environment contribution to variability of this trait, while the genetic
      contribution accounted for 60.6% regardless of the 4 classes of relatives. Taking
      the three polymorphisms into account did not modify the variance components.
      These results show that plasma VEGF concentrations are under genetic control in
      healthy families and that none of the 3 candidate polymorphisms significantly
      altered heritability.

PMID- 17227477
TI  - Molecular variability of the 16p13.3 region in Amerindians and its
      anthropological significance.
AB  - A total of 1558 base pairs in the 16p13.3 region were investigated in 98
      individuals of Mongolian, Northern Arctic and Amerindian affiliation, and the
      results compared with those obtained in a previous worldwide study of the same
      genomic region. Fifty-five polymorphic sites could be classified into thirty-five
      haplotypes from the total data. A median joining network based on the haplotypes
      revealed two distinct clusters: one with low diversity, with haplotypes found in
      all five geographic-ethnic categories; while the other, with the most divergent
      haplotypes, was composed mainly of Africans and a few Amerindians. Almost all
      neutrality parameters yielded significantly negative values. Demographic
      simulations with the exclusively Amerindian dataset rejected all scenarios,
      including a bottleneck beginning more than 12,000 years ago. The demographic
      scenarios tested considering population growth were similar among the Amerindian
      and worldwide or Eurasian data sets. The results suggest that Amerindians are a
      representative sample of Eurasian populations, preserving the signal of
      demographic growth from the out of Africa exodus and, together with data from
      uniparental markers, support a scenario of a bottleneck of moderate intensity
      during the peopling of the New World.

PMID- 17227478
TI  - Dissecting the genetic history of Sao Tome e Principe: a new window from Y
      chromosome biallelic markers.
AB  - Twenty biallelic Y chromosome markers were analyzed in Angolares, Forros and
      Tongas, three population groups from the African archipelago of Sao Tome e
      Principe. While most male lineages belonged to sub-Saharan haplogroups, the
      component of European origin added up 23.9% in the archipelago. This contrasts
      with the reported absence of European mtDNA lineages, and the combined findings
      testify to a strong sex-biased admixture process during the long-lasting colonial
      period in Sao Tome e Principe. Furthermore, the male mediated European component
      was clearly found to be out of proportion to the small demographic impact of the
      Portuguese on the islands, reflecting high variance in the reproductive success
      of the individuals that contributed to its peopling. The male portion of European
      ancestry was 33.3% in Forros, 27.3% in Tongas and approximately two-fold less,
      14.5%, in Angolares. The Angolares also showed the lowest haplogroup diversity
      and the most reduced number of different haplogroups. The current results
      reinforce our previous evidence pointing to remarkable restrictions in gene flow
      between Angolares and other Sao Tomean inhabitants, in agreement with their
      considerable isolation and confinement to the south-eastern tip of Sao Tome until
      recently.

PMID- 17227479
TI  - Influence of the Angiotensin II type I receptor gene 1166A > C polymorphism on BP
      and aortic pulse wave velocity among Malays.
AB  - Angiotensin II type 1 receptor (AGT1R) gene 1166A > C polymorphism has been shown
      to be associated with essential hypertension and aortic stiffness as measured by
      carotid femoral pulse wave velocity (PWV). This study was carried out to
      investigate the association of the 1166A > C polymorphism with blood pressure
      (BP) and PWV among Malay hypertensive and normotensive subjects. Two hundred and
      one hypertensive subjects without evidence of cardiovascular (CV) complications
      and 201 age- and sex-matched normotensive subjects were studied in a cross
      sectional design. Blood pressures (BP) and PWV were measured, and 1166A > C
      genotype was determined by polymerase chain reaction followed by restriction
      enzyme digestion. The 1166C allele frequency was 7.96% and 7.73% among Malay
      hypertensive and normotensive subjects, respectively. There was no association of
      the 1166A > C polymorphism with BP in the hypertensive, normotensive or overall
      Malay populations. PWV was significantly higher among 1166C allele carriers as
      compared to non-carriers (10.52 +/- 1.82 vs. 10.15 +/- 1.80, p = 0.040) in the
      overall population, but not in the hypertensive and normotensive populations
      separately. In conclusion, the frequency of 1166C polymorphism is similar among
      Malay hypertensive and normotensive subjects. This polymorphism has no
      association with BP but may have an influence on PWV in Malays, which needs
      further investigation.

PMID- 17227480
TI  - Regression-based multivariate linkage analysis with an application to blood
      pressure and body mass index.
AB  - Multivariate linkage analysis has been suggested for the analysis of correlated
      traits, such as blood pressure (BP) and body mass index (BMI), because it may
      offer greater power and provide clearer results than univariate analyses.
      Currently, the most commonly used multivariate linkage methods are extensions of
      the univariate variance component model. One concern about those methods is their
      inherent sensitivity to the assumption of multivariate normality which cannot be
      easily guaranteed in practice. Another problem possibly related to all
      multivariate linkage analysis methods is the difficulty in interpreting nominal p
      values, because the asymptotic distribution of the test statistic has not been
      well characterized. Here we propose a regression-based multivariate linkage
      method in which a robust score statistic is used to detect linkage. The p-value
      of the statistic is evaluated by a simple and rapid simulation procedure.
      Theoretically, this method can be used for any number and type of traits and for
      general pedigree data. We apply this approach to a genome linkage analysis of
      blood pressure and body mass index data from the Beaver Dam Eye Study.

PMID- 17227481
TI  - Two-sample comparison based on prediction error, with applications to candidate
      gene association studies.
AB  - To take advantage of the increasingly available high-density SNP maps across the
      genome, various tests that compare multilocus genotypes or estimated haplotypes
      between cases and controls have been developed for candidate gene association
      studies. Here we view this two-sample testing problem from the perspective of
      supervised machine learning and propose a new association test. The approach
      adopts the flexible and easy-to-understand classification tree model as the
      learning machine, and uses the estimated prediction error of the resulting
      prediction rule as the test statistic. This procedure not only provides an
      association test but also generates a prediction rule that can be useful in
      understanding the mechanisms underlying complex disease. Under the set-up of a
      haplotype-based transmission/disequilibrium test (TDT) type of analysis, we find
      through simulation studies that the proposed procedure has the correct type I
      error rates and is robust to population stratification. The power of the proposed
      procedure is sensitive to the chosen prediction error estimator. Among commonly
      used prediction error estimators, the .632+ estimator results in a test that has
      the best overall performance. We also find that the test using the .632+
      estimator is more powerful than the standard single-point TDT analysis, the
      Pearson's goodness-of-fit test based on estimated haplotype frequencies, and two
      haplotype-based global tests implemented in the genetic analysis package FBAT. To
      illustrate the application of the proposed method in population-based association
      studies, we use the procedure to study the association between non-Hodgkin
      lymphoma and the IL10 gene.

PMID- 17227482
TI  - Variation of estimates of SNP and haplotype diversity and linkage disequilibrium
      in samples from the same population due to experimental and evolutionary sample
      size.
AB  - Studies of genetic polymorphisms and diversity between and within human
      populations are increasingly characterised by a very large number of genetic
      markers but using a relatively small number of individuals from which DNA samples
      were taken. In this report we examine the limitations of a small experimental
      sample size relative to a large genomic sample size, and quantify the sampling
      variance of a number of measures of diversity and linkage disequilibrium. The
      relationship between sample size and observed levels of polymorphism and
      haplotype diversity at the level of a gene is investigated under a neutral model
      of sequence evolution, using coalescent simulations. It is shown that the effect
      of evolutionary sampling, as manifested by differences between samples (genes) in
      measures of diversity estimated using very large sample sizes, is substantial,
      with a coefficient of variation of the number of detected polymorphic SNPs or
      haplotypes in the order of 15%. The effect of experimental design (sample size)
      is also very large, and a number of 'significant' results reported in the
      literature can be explained by sampling alone. The expected correlation
      coefficient of measures of linkage disequilibrium across samples from the same
      population has been quantified and found to be consistent with empirical
      estimates from the literature.

PMID- 17227484
TI  - A conversation between Peter Puchner and John K. Lattimer.

PMID- 17227485
TI  - Renal ischaemia: not a problem in laparoscopic partial nephrectomy?

PMID- 17227486
TI  - Informed consent: are we deluding ourselves? A randomized controlled study.

PMID- 17227488
TI  - Mentoring in laparoscopic urology.

PMID- 17227487
TI  - Young men with prostate cancer: are they different and how should they be
      managed?

PMID- 17227489
TI  - Vertical rectus abdominis flap reconstruction in patients with advanced penile
      squamous cell carcinoma.
AB  - OBJECTIVES: To evaluate the role of radical surgical debridement and excision
      with a vertical rectus abdominis myocutaneous (VRAM) flap reconstruction in
      patients with advanced penile cancer and subcutaneous metastatic disease, as the
      quality of life in such patients is extremely poor, multimodal treatments often
      fail and the outlook for the patient is limited with the development of
      uncontrollable disease. PATIENTS AND METHODS: Four patients with advanced penile
      cancer presenting with fungating, cutaneous tumour deposits received palliative
      surgical resections for abdominal and inguinal disease. A VRAM flap was used in
      all cases to achieve tissue coverage. RESULTS: All grafts were viable and the
      mean inpatient stay was 14 days. There were no immediate complications after
      surgery; patient satisfaction and symptom relief was excellent. CONCLUSIONS:
      Aggressive palliative resection with a VRAM can dramatically improve the
      patients' quality of life in advanced penile cancer, permitting disease control
      with satisfactory cosmesis. However, a multidisciplinary approach involving both
      the urological reconstructive and plastic surgeon is essential.

PMID- 17227490
TI  - Validity of prostate-specific antigen as a tumour marker in men with prostate
      cancer managed by watchful-waiting: correlation with findings at serial
      endorectal magnetic resonance imaging and spectroscopic imaging.
AB  - OBJECTIVE: To investigate the validity of prostate-specific antigen (PSA) as a
      tumour marker in men with clinically localized prostate cancer who have selected
      watchful waiting, by determining if serial PSA level measurements are correlated
      with findings of malignancy or benign prostatic hyperplasia (BPH) at serial
      endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopic
      imaging (MRSI). PATIENTS AND METHODS: We retrospectively identified 69 men with
      biopsy-proven prostate cancer being managed by watchful waiting, who underwent
      serial endorectal MRI/MRSI and who had contemporaneous serial PSA measurements.
      The mean (range) follow-up was 392 (294-571) days. A panel of three experienced
      readers reviewed the initial and follow-up MRI/MRSI studies, and classified
      findings of prostate cancer as stable or progressive. Another reader assessed BPH
      by calculating total gland and central gland volumes on all studies. RESULTS: At
      the follow-up MRI/MRSI, 51, 17 and one patient had stable, progressive, or
      unevaluable prostate cancer, respectively. The mean PSA velocity was
      significantly greater in patients with radiologically progressive disease (1.42
      vs 0.42 ng/mL/year, P = 0.04). A PSA velocity of >0.75 ng/mL/year identified
      those with radiologically progressive disease with a true-positive fraction of
      0.71 and a false-positive fraction of 0.39. PSA levels were not correlated with
      changes in total or central gland volumes (P > 0.05). CONCLUSIONS: In men with
      clinically localized prostate cancer who select watchful waiting, serial PSA
      levels are correlated with findings of malignancy but not BPH at serial
      endorectal MRI/MRSI, suggesting that PSA is a useful longitudinal tumour marker
      in this population.

PMID- 17227491
TI  - Prostate cancer detection in men with an initial diagnosis of atypical small
      acinar proliferation.
AB  - OBJECTIVE: To determine the subsequent prostatic adenocarcinoma detection rate
      amongst men with an initial diagnosis of atypical small acinar proliferation
      (ASAP). PATIENTS AND METHODS: We reviewed the Illawarra Prostate Pathology
      Database over a 10-year period (January 1994 to January 2004) for specimens
      diagnosed as ASAP. These specimens were re-reviewed and clinical data obtained.
      RESULTS: Of 61 cases of ASAP, there were complete follow-up data for 31. In this
      group nine patients had no further biopsies at our institution; the other 22 had
      at least one repeat biopsy. The incidence of prostatic adenocarcinoma in this
      group was 17/31 (55%). This included 13 diagnoses on second biopsy, three on
      third biopsy and one diagnosed at another institution. CONCLUSION: This study
      showed a detection rate for prostatic adenocarcinoma of 55% after an initial
      diagnosis of ASAP, which indicates that an initial diagnosis of ASAP mandates re
      biopsy.

PMID- 17227492
TI  - Transdermal oestrogen therapy as a second-line hormonal intervention in prostate
      cancer: a bad experience.
AB  - OBJECTIVE: To compare transdermal oestrogen with oral diethylstilbestrol (DES) as
      a second- or third-line hormonal therapy in the treatment of prostate cancer.
      PATIENTS AND METHODS: In all, 32 assessable patients who, having already had a
      relapse on at least one line of hormonal therapy, received transdermal oestrogen
      therapy as an alternative to oral DES, when DES became unavailable. RESULTS:
      Whereas DES had controlled the prostate-specific antigen (PSA) level for a median
      of 29 weeks in a group of 15 patients in remission, all but one had an increase
      in PSA level (median 86% increase above the starting PSA level) within a median
      of 8 weeks after introducing transdermal therapy. This increase was reversed in
      seven of the 12 patients who recommenced DES therapy. CONCLUSION: Although the
      use of transdermal oestrogen is currently attracting enthusiasm as a first-line
      treatment for prostate cancer, these results show that for second- or third-line
      therapy further cautious research with careful monitoring is necessary.

PMID- 17227494
TI  - A prospective evaluation of the short-term impact and recovery of health-related
      quality of life in men undergoing radical prostatectomy.
AB  - OBJECTIVE: To prospectively evaluate the acute and short-term effects of radical
      retropubic prostatectomy (RRP) on health-related quality of life (HRQoL) using a
      validated generic HRQoL instrument that measures overall health status, as
      although there is increasing interest in the HRQoL of patients being treated for
      prostate cancer, most studies have focused on long-term outcomes. PATIENTS AND
      METHODS: In all, 121 men undergoing RRP for clinically localized prostate cancer
      were prospectively evaluated for short-term HRQoL using an acute Short Form-12
      version-2 Physical and Mental Health Survey Acute Form before and serially each
      week from 1 to 6 weeks after RRP. The physical (PCS) and mental component score
      (MCS) were calculated from the questionnaires at each time and the data analysed
      by random coefficient modelling. Separate models were fitted for MCS and PCS
      using covariates of race, age, estimated blood loss (EBL), time after RRP, and
      their interaction terms. RESULTS: The PCS initially declined and improved
      linearly. and the baseline level was not achieved by 6 weeks, but modelling lines
      showed an expected return to baseline at 7-8 weeks for all patients. Age had a
      significant relationship with the PCS; older men (>60 years) scored higher, and
      their PCS remained significantly higher after RRP than younger men (< or =60
      years) until 5 weeks. EBL also had a significant relationship with PCS; men with
      an EBL of >500 mL had a significantly lower PCS at 1 week and this remained
      significantly lower than for men with an EBL of < or = 500 mL until approximately
      7 weeks. The MCS improved immediately after RRP and remained higher throughout
      the study than at baseline. Race was the only covariate for which there were
      significant differences in the MCS. The MCS was significantly lower at baseline
      for African-Americans than for Caucasian Americans, and remained lower until 6
      weeks after RRP. CONCLUSIONS: There were significant changes in HRQoL during in
      the short-term after RRP. Younger men and those with a higher EBL might have a
      slower recovery of the PCS after RRP. African-Americans had a slower increase in
      MCS and might have a different initial emotional or mental health response to RRP
      than have Caucasians.

PMID- 17227493
TI  - Early effects of pharmacological androgen deprivation in human prostate cancer.
AB  - OBJECTIVES: To assess the early histological effects of pharmacological androgen
      deprivation (AD), which have been assessed only over longer periods, as surgical
      castration leads rapidly to diminished cell proliferation and enhanced cell death
      within the prostate. PATIENTS AND METHODS: With Institutional Review Board
      approval, 35 patients were randomly assigned (seven in each group) to receive 0,
      7, 14, 21 and 28 days of AD (flutamide, 250 mg orally three times/day, and one
      injection with leuprolide acetate 7.5 mg) before radical prostatectomy. The
      surgical specimens were assessed by conventional histology and
      immunohistochemistry, while macroarray analysis and quantitative real-time
      polymerase chain reaction (QRT-PCR) were used to examine gene expression.
      RESULTS: There were morphological changes within the prostatic tissues as early
      as 7 days after initiating AD, similar to the response to castration. There was
      tumour cell vacuolization indicating cellular injury, glandular atrophy and
      mononuclear cell infiltration as prominent and progressive effects but, by
      contrast with castration studies, there were no changes in epithelial
      proliferation or apoptosis. Macroarray analysis, validated by QRT-PCR and
      immunohistochemistry, showed up-regulation of numerous and potentially counter
      effective genes involved in the cell cycle and apoptosis. CONCLUSIONS:
      Pharmacological AD induces significant involution within prostatic tissues over 7
      28 days, but allows the persistence of some viable tumour cells capable of
      proliferation.

PMID- 17227495
TI  - Correlation between risk factors for vascular disease and the American Urological
      Association Symptom Score.
AB  - OBJECTIVE: To evaluate the correlation between risk factors for vascular disease
      and the American Urological Association Symptom Score (AUA-SS), by comparing the
      presence of these risk factors with the degree of lower urinary tract symptoms
      (LUTS). PATIENTS AND METHODS: We retrospectively reviewed the medical history,
      AUA-SS, and prostate volume of men who had a radical prostatectomy. The degree of
      LUTS in men with and without risk factors for cardiovascular disease was
      compared. RESULTS: The mean AUA-SS was 7.2 for the entire cohort, 5.6 in men with
      no risk factors, and 7.9 in men with at least one risk factor (P < 0.05). In men
      with one to four risk factors, the mean AUA-SS was 6.9, 7.9, 10.7, and 19.5,
      respectively. There was no correlation between the AUA-SS and prostate size in
      the entire cohort or among any groups. CONCLUSIONS: Men with risk factors for
      vascular disease are more likely to have a higher AUA-SS than men without these
      risk factors. These findings suggest the possibility of an association between
      vascular disease and the development and severity of LUTS in men.

PMID- 17227496
TI  - Redefining response in overactive bladder syndrome.
AB  - OBJECTIVE: To evaluate three potential definitions of treatment response in
      overactive bladder (OAB) syndrome, based on the International Continence Society
      (ICS) definition of OAB, using pooled data from two large clinical trials of the
      antimuscarinic agent solifenacin succinate. PATIENTS AND METHODS: As the ICS
      definition of OAB does not rely on urodynamic observations for a diagnosis, the
      use of composite endpoints, such as in the definitions examined here, might
      provide a more relevant measure of patient benefits. Each definition was tested
      to assess the impact of pharmacotherapy, comparing treatment response rates based
      on composite endpoints. Responder definitions were validated based on the impact
      on quality of life (QoL). Pooled data from two 12-week multinational,
      multicentre, double-blind randomized studies of solifenacin, a once-daily oral
      antimuscarinic for treating OAB symptoms, were used for this analysis. Based on
      the symptom data from these studies (episodes of urgency, incontinence, nocturia
      and voiding frequency per 24 h), response was defined as being: (i) a reduction
      by half or more in all baseline symptoms; (ii) a reduction by half or more in
      urgency and at least one other symptom; or (iii) resolution of urgency episodes
      and at least one other symptom. Health-related QoL changes were recorded using
      the King's Health Questionnaire (KHQ). RESULTS: Solifenacin at 5 mg or 10 mg once
      daily resulted in significantly higher response rates than with placebo,
      irrespective of the definition of a responder (P < or = 0.001). When assessing
      the most challenging definition of response (resolution of urgency and at least
      one other symptom), solifenacin at 5 mg and 10 mg resulted in 20% and 25% of
      patients, respectively, meeting the response criteria, vs 12% of placebo-treated
      patients (P < or = 0.001 for both solifenacin doses). For all three definitions
      of response, responders showed greater improvements in all KHQ domains than did
      nonresponders, and the differences were statistically significant. CONCLUSIONS:
      The two strictest definitions of response (halving or more in all baseline
      symptoms or resolution of urgency and more than one other symptom) appeared to
      capture QoL changes most effectively. Establishing the most appropriate
      definition to assess treatment-related changes in OAB will require further
      investigation, but it is clear from this analysis that composite clinical
      endpoints, based on the ICS definition of OAB, are a valid approach for assessing
      the effect of treatments for OAB.

PMID- 17227497
TI  - The penile suspensory ligament: abnormalities and repair.
AB  - OBJECTIVE: To assess men presenting with abnormalities of the penile suspensory
      ligament (PSL) and its correction. PATIENTS AND METHODS: In all, 35 men
      presenting with abnormalities of the PSL that were subsequently repaired were
      included in this series. The causes included; sexual trauma (15 men), congenital
      absence of the PSL/congenital penile curvature (14), and two each with venogenic
      erectile dysfunction, Peyronie's disease and penile dysmorphic disorder. The
      diagnosis was made clinically by the presence of a palpable gap between the
      symphysis pubis and the penis, together with medical history and examination of
      penile torsion or instability. The surgical repair used nonabsorbable sutures
      placed between the symphysis pubis and the tunica albuginea of the penis.
      RESULTS: A 'good' surgical outcome was defined as correction of the penile
      deformity or instability and achieving normal sexual function. There was a good
      surgical outcome in 91% of men as defined, and 86% of the men were happy with the
      outcome. There were no significant complications, but three men needed a repeat
      PSL repair. CONCLUSION: Men with abnormalities of the PSL can present with a
      variety of clinical symptoms, but when correctly diagnosed the repair is a simple
      technique with a successful cosmetic and functional outcome.

PMID- 17227498
TI  - The influence of age on treatment outcomes in men with erectile dysfunction
      treated with two regimens of tadalafil: results of the SURE study.
AB  - OBJECTIVE: To evaluate whether patterns of sexual activity and efficacy over time
      to two dosing regimens of tadalafil differ with ageing in men with erectile
      dysfunction (ED). PATIENTS AND METHODS: The SURE study was a multicentre,
      crossover, open-label study. In all, 4262 men with ED were randomly assigned to
      treatment with tadalafil 20 mg on-demand before sexual activity, or three times
      per week for 5-6 weeks. After a 1-week washout period, patients were crossed over
      to the alternative regimen for 5-6 weeks. This post hoc analysis evaluated the
      pattern of sexual attempts, efficacy and safety of these two regimens of
      tadalafil across several age groups. RESULTS: The mean number of sexual attempts
      per week decreased from a range of 2.6-2.8 at age < or = 40 years to 1.9 at age
      >70 years. Age did not significantly influence the time of sexual activity after
      dosing. A high percentage of attempts occurred >4 h after dosing for all age
      groups ( approximately 70% for men taking tadalafil three times per week and
      approximately 50% for men taking tadalafil on-demand). For all age groups, most
      attempts took place in the late evening. The mean per-patient rate of successful
      attempts was similar for each interval up to 36 h after dosing and decreased with
      increasing age (> or =75% at age < or = 60 years, > or = 68% at age >60 to < or =
      70 years, and > or = 60% at age >70 years). Tadalafil was well tolerated at all
      ages. CONCLUSIONS: Patterns of sexual activity with tadalafil 20 mg, taken on
      demand or three times per week, were similar in the different age groups.
      Tadalafil was effective up to 36 h after dosing for all age groups.

PMID- 17227499
TI  - Digital three-dimensional modelling of the male pelvis and bicycle seats: impact
      of rider position and seat design on potential penile hypoxia and erectile
      dysfunction.
AB  - OBJECTIVE: To digitally model (three-dimensional, 3D) the course of the pudendal
      arteries relative to the bony pelvis in the adult male, and to identify sites of
      compression with different bicycle riding positions as a potential cause of
      penile hypoxia and erectile dysfunction. SUBJECTS AND METHODS: 3D models were
      made from computed tomography scans of one adult male pelvis (a healthy
      volunteer) and three bicycle seats. Models were correlated with lateral
      radiographs of a seated rider to determine potential vascular compression between
      the bony pelvis and seats at different angles of rider positioning. RESULTS:
      Pelvis/seat models suggest that the most likely site of compression of the
      internal pudendal artery is immediately below the pubic symphysis, especially
      with the rider leaning forward. For an upright rider, the internal pudendal
      arteries do not appear to be compressed between the seat and the bony pelvis.
      Leaning partly forward with arms extended, the seat/symphysis areas were reduced
      to 73 mm(2) with standard seat and 259 mm(2) with a grooved seat. Leaning fully
      forward, the seat/symphysis areas decreased (no space with standard seat; 51
      mm(2) with a grooved seat) and both the ischial tuberosities and the pubic
      symphysis might be in contact with the seat. CONCLUSION: A grooved seat allows
      better preservation of the seat/symphysis space than a standard seat, but the
      rider's position is more important for preserving the seat-symphysis space (and
      reducing compression) than is seat design alone. Any factors which influence the
      seat-symphysis space (including an individual's anatomy, seat design and rider
      position) can increase the potential for penile hypoxia and erectile
      dysfunction/perineal numbness.

PMID- 17227500
TI  - The effects of cyclical oestrogen on bladder and urethral structure and function.
AB  - OBJECTIVE: To determine the effects of cycling oestrogen in rabbits, as oestrogen
      is essential for physiological maintenance and integrity of the female urogenital
      tract. MATERIALS AND METHODS: Changes in circulating oestrogen have marked
      effects on the bladder of experimental animals, with ovariectomy (Ovx) inducing
      smooth muscle (SM) and mucosal atrophy, increasing collagen synthesis and
      deposition, decreasing contractile function, mucosal and SM blood flow; oestrogen
      reverses these effects and increases bladder mass and SM density, primarily by
      stimulating angiogenesis and increasing blood flow. Twenty adult female New
      Zealand White rabbits were divided into five equal groups; group 1 served as the
      control group, and groups 2-5 had a bilateral Ovx. Group 2 received no oestradiol
      and was assessed 2 weeks after Ovx; groups 3-5 received 17-beta oestradiol from a
      subcutaneous slow-release tablet 2 weeks after Ovx, which remained in place for a
      subsequent 2-week period. Group 3 was then assessed after the 2 weeks on
      oestradiol. Groups 4 and 5 then had their oestradiol tablets removed for 2 weeks
      and group 4 was assessed after this period off oestradiol. Group 5 then received
      a new oestradiol tablet that was left in place for an additional 2 weeks.
      RESULTS: Both groups receiving oestrogen (3 and 5) had a statistically
      significantly greater bladder weight than both the control group and group 2. The
      volume fraction of SM paralleled the bladder weight, showing that oestrogen
      increased the volume fraction of SM whereas Ovx and low oestrogen decreased the
      SM fraction. The cross-sections of the urethra from groups 3 and 5 were
      significantly wider than those of either the control or group 1, also being
      consistent with the structural effects of oestrogen. Intra-arterial phenylephrine
      increased urethral pressure to a similar level in all groups. The urethral
      pressure response to intra-arterial acetylcholine shifted from contraction in the
      control to relaxation in the oestrogen-treated groups. Ovx resulted in a lower
      vascular density, whereas oestrogen resulted in a significant increase in
      vascular density (angiogenesis). CONCLUSIONS: Cyclical oestrogen had pronounced
      structural and pharmacological effects. Low oestrogen decreased the volume
      fraction of SM, increased collagen, and decreased vasculature, whereas oestrogen
      mediated a marked hypertrophy of the SM components, decreased the collagen
      component, and stimulated angiogenesis. Cyclical oestrogen also had marked
      effects on the responses to intra-arterial acetylcholine, shifting the response
      from contraction to relaxation.

PMID- 17227501
TI  - Anything new for the ladies in 2007?

PMID- 17227502
TI  - Importance of peripheral biopsies in maximising the detection of early prostate
      cancer in repeat 12-core biopsy protocols.

PMID- 17227503
TI  - Immunostaining for placental alkaline phosphatase on fine-needle aspiration
      specimens to detect noninvasive testicular cancer: a prospective evaluation in
      cryptorchid men.

PMID- 17227504
TI  - Computed tomography urography for diagnosing bladder cancer.

PMID- 17227506
TI  - The treatment of female bladder outlet obstruction.

PMID- 17227508
TI  - Gene expression profiling of the human prostate zones.

PMID- 17227510
TI  - Surgical Atlas. Percutaneous nephrolithotomy: the Mannheim technique.

PMID- 17227512
TI  - Pro: Anorectal testing is useful in fecal incontinence.

PMID- 17227513
TI  - Con: Anorectal manometry and imaging are not necessary in patients with fecal
      incontinence.

PMID- 17227514
TI  - A balancing view: Fecal incontinence: test or treat empirically--which strategy
      is best?

PMID- 17227515
TI  - Esophageal stricture: incidence, treatment patterns, and recurrence rate.
AB  - OBJECTIVES: We aimed to determine the incidence, natural history, and recurrence
      rate of esophageal stricture diagnosed in primary care. METHODS: From the U.K.
      General Practice Research Database, we identified patients with a stricture
      diagnosis recorded between 1994 and 2000. Diagnoses were confirmed by general
      practitioner-completed questionnaires. Patients with stricture were compared to
      an age- and sex-matched sample of controls from the original source population.
      We estimated the incidence of stricture, potential risk factors, and
      comorbidities, and relative risk (RR) for subsequent stricture recurrence and
      mortality. RESULTS: The incidence of esophageal stricture was 1.1 per 10,000
      person-years and increased markedly with age. Incidence of stricture decreased
      from 1994 to 2000, concomitant with a substantial increase in proton pump
      inhibitor (PPI) use. The majority of stricture cases (68%) were peptic. Prior
      dysphagia, gastroesophageal reflux disease (GERD), hiatus hernia, peptic ulcer
      disease, and heavy alcohol use were associated with an increased risk of
      stricture. The rate of stricture recurrence was 11.1 per 100 person-years. Risk
      of recurrence associated with long-term PPI use adjusting for other factors was
      0.6 (95% CI 0.3-1.1). Mortality in patients with peptic stricture was similar to
      that in the control population. CONCLUSIONS: Esophageal stricture is a rare
      event, and most cases in primary care are peptic strictures. Prior GERD, hiatus
      hernia, and peptic ulcer are associated with an increased risk of peptic
      stricture. Incidence of stricture decreased from 1994 to 2000.

PMID- 17227516
TI  - Office-based unsedated small-caliber endoscopy is equivalent to conventional
      sedated endoscopy in screening and surveillance for Barrett's esophagus: a
      randomized and blinded comparison.
AB  - OBJECTIVES: A major limitation to screening and surveillance of Barrett's
      esophagus is the complexity, expense, and risk associated with sedation for upper
      endoscopy. This study examines the feasibility, accuracy, and patient
      acceptability of office-based unsedated endoscopy as an alternative. METHODS: Of
      274 eligible adults scheduled for endoscopic screening for gastroesophageal
      reflux symptoms or surveillance of Barrett's esophagus at a tertiary care center,
      121 underwent unsedated small-caliber endoscopy and conventional endoscopy in a
      randomized crossover study. The two procedures were compared with regard to
      histological detection of Barrett's esophagus and dysplasia and biopsy size.
      Patients answered questionnaires assessing the tolerability of the procedures.
      RESULTS: The prevalence of Barrett's esophagus was 26% using conventional
      endoscopy and 30% using unsedated endoscopy (P= 0.503). The level of agreement
      between the two approaches was "moderate" (kappa= 0.591). Each modality detected
      four cases of low-grade dysplasia with concordance on one case. The tissue
      samples collected with unsedated endoscopy were smaller than with conventional
      endoscopy (P < 0.001). The majority of subjects rated their experience with both
      procedures as being well tolerated with minimal or no difficulty. When asked
      which procedure they would prefer in the future, 71% (81/114) chose unsedated
      small-caliber endoscopy. CONCLUSIONS: Office-based unsedated small-caliber
      endoscopy is technically feasible, well tolerated, and accurate in screening for
      Barrett's esophagus, despite yielding a smaller biopsy specimen. This approach
      bears the potential to eliminate the infrastructure and cost required for
      intravenous sedation in this application.

PMID- 17227517
TI  - Comparative study of conventional colonoscopy, chromoendoscopy, and narrow-band
      imaging systems in differential diagnosis of neoplastic and nonneoplastic colonic
      polyps.
AB  - AIM: To identify the feasibility of the narrow-band imaging (NBI) method compared
      with that of conventional colonoscopy and chromoendoscopy for distinguishing
      neoplastic and nonneoplastic colonic polyps. METHOD: This study enrolled
      consecutive patients who underwent colonoscopy using a conventional colonoscope
      between January and February 2006 at Chang-Gung Memorial Hospital, Linkou Medical
      Center, Taiwan. These 78 patients had 110 colorectal polyps. During the
      procedure, conventional colonoscopy first detected lesions, and then the NBI
      system was used to examine the capillary networks. Thereafter indigo carmine
      (0.2%) was sprayed directly on the mucosa surface prior to evaluating the crypts
      using a conventional colonoscope. The pit patterns were characterized using the
      classification system proposed by Kudo. Finally, a polypectomy or biopsy was
      performed for histological diagnosis. RESULTS: Of the 110 colorectal polyps, 65
      were adenomas, 40 were hyperplastic polyps, and five were adenocarcinomas. The
      NBI system and pit patterns for all lesions were analyzed. For differential
      diagnosis of neoplastic (adenoma and adenocarcinoma) and nonneoplastic
      (hyperplastic) polyps, the sensitivity of the conventional colonoscope for
      detecting neoplastic polyps was 82.9%, specificity was 80.0% and diagnostic
      accuracy was 81.8%, significantly lower than those achieved with the NBI system
      (sensitivity 95.7%, specificity 87.5%, accuracy 92.7%) and chromoendoscopy
      (sensitivity 95.7%, specificity 87.5%, accuracy 92.7%). Therefore, no significant
      difference existed between the NBI system and chromoendoscopy during differential
      diagnosis of neoplastic and nonneoplastic polyps. CONCLUSION: The NBI system
      identified morphological details that correlate well with polyp histology by
      chromoendoscopy.

PMID- 17227518
TI  - Hold on Picasso, narrow band imaging is here.
AB  - The goal of colonoscopy is to identify and remove premalignant and malignant
      polyps. During colonoscopy it is not feasible to differentiate with certainty if
      a polyp is benign or premalignant, resulting in removal of all polyps via
      polypectomy. In attempts to overcome this clinical dilemma, techniques such as
      chromendoscopy have been developed to aid in improving the accuracy of
      identifying precancerous polyps. Chromendoscopy helps detect suspicious polyps
      using a dye spraying technique, but it is time consuming and causes collateral
      distortion of the adjacent mucosal field. Recently, narrow band imaging (NBI) has
      been able to highlight abnormal mucosal topography and microvasculature by
      illuminating with narrow range blue light. This is achieved with the click of a
      button on the endoscope, and the accuracy of differentiating between abnormal and
      normal mucosa is equivalent to chromendoscopy. NBI and other similar technologies
      will likely provide an electronic, easier alternative to chromoendoscopy to aid
      the endoscopist in differentiation among benign, premalignant, and malignant
      mucosal patterns.

PMID- 17227519
TI  - Afternoon colonoscopies have higher failure rates than morning colonoscopies.
AB  - BACKGROUND: There are several known predictors of an incomplete colonoscopy or
      difficult colonoscopy. In addition, inadequate bowel preparation has been
      reported in procedures scheduled later in the day. Operator fatigue, which tends
      to be higher as the day passes on, may also impact colonoscopy completion rate.
      AIMS: To determine the influence of performing outpatient colonoscopies in the
      afternoon versus morning on the completion rates of colonoscopy and adequacy of
      bowel preparation. METHODS: Retrospective chart review of all outpatient
      colonoscopies performed between November 2003 and October 2004 in the Division of
      Gastroenterology at MetroHealth Medical Center in Cleveland, Ohio. Patient
      demographics, indications for procedure, and colonoscopic findings were reviewed.
      Patients received polyethylene glycol electrolyte-based bowel preparation in the
      evening prior to the day of the scheduled colonoscopy. RESULTS: A total of 2,087
      colonoscopies was performed, of which 1,084 were in the morning and 999 were in
      the afternoon. Patients in the morning and afternoon were similar in regards to
      the known risk factors predictive of an incomplete colonoscopy. The incompletion
      rate was significantly higher in the afternoon compared to the morning (6.5% vs
      4.1%, P= 0.013, OR for incompletion was 1.64, CI 1.11-2.44). Inadequate bowel
      preparation was found in 167 out of 1,084 (15.4%) colonoscopies in the morning
      and 197 out of 999 (19.7%) colonoscopies in the afternoon (P= 0.011). Even after
      excluding incomplete colonoscopies due to poor bowel preparation precluding
      examination, the incompletion rate was still higher in the afternoon (5% vs 3.2%,
      P= 0.043, OR 1.60, CI 1.03-2.51). CONCLUSIONS: Scheduling of colonoscopies in the
      afternoon compared to the morning may be an independent predictor of an
      incomplete colonoscopy and inadequate bowel preparation. According to our study
      findings, scheduling of all outpatient colonoscopies preferentially in the
      morning would avoid suboptimal procedures in 5% of patients and the need for
      unnecessary repeat colonoscopy or an alternative imaging study in 2.4% of
      patients.

PMID- 17227520
TI  - Evaluation of F-actin ELISA for the diagnosis of autoimmune hepatitis.
AB  - OBJECTIVE: Antibodies to F-actin have been proposed to increase specificity in
      the diagnosis of autoimmune hepatitis (AIH). We compared the diagnostic value of
      a new F-actin enzyme-linked immunosorbent assay (ELISA) with the current gold
      standard of detection of smooth muscle antibodies by indirect immunofluorescence
      (SMA-IFT). METHODS: Archived sera of 47 patients with SMA positive AIH were
      tested with the F-actin ELISA and SMA-IFT. Prospectively collected sera of 123
      patients with various liver diseases, 35 of whom had AIH, were analyzed by both
      assays. Different cutoff limits were considered for the F-actin ELISA (increments
      between 20 and 60 ELISA units) and SMA-IFT (titers of 1:40, 1:80, and 1:160).
      RESULTS: The F-actin ELISA had a sensitivity of 100% to detect all of 47 SMA
      positive AIH sera and the value of the ELISA units correlated with that of SMA
      titers (p < 0.0001). In prospective analysis, F-actin ELISA showed a superior
      sensitivity (74% vs 34%) and a similar specificity (98% vs 99%) and positive
      predictive value (88% vs 92%), compared with SMA-IFT. Combining both assays
      improved neither sensitivity nor specificity. CONCLUSIONS: The new F-actin ELISA
      seems to be a useful diagnostic tool with similar specificity and superior
      sensitivity for the diagnosis of AIH, compared with standard SMA-IFT. Due to its
      simplicity and operator independency, the F-actin ELISA may become a preferred
      screening technique for detection of autoantibodies in patients with suspected
      AIH.

PMID- 17227521
TI  - The emerging importance of chronic hepatitis C infection in Asian Americans.
AB  - OBJECTIVES: To study the demographics, epidemiology, and natural history of
      chronic hepatitis C in Asian Americans. METHODS: This retrospective survey
      describes 260 Asian Americans with chronic hepatitis C referred to one tertiary
      center. RESULTS: Ninety-two percent of patients were born in Asia. Fifty-one
      percent reported a history of unsafe therapeutic injections, which was a risk
      factor only in those with exposure outside the United States (p < 0.0001). A
      history of transfusion was reported in 41% of patients and was more frequent in
      those with exposure within the Unites States (p < 0.0001). Only 3.8% reported a
      history of intravenous drug abuse, which was more frequent in those with exposure
      within the United States (p < 0.0001). Hepatitis C genotype 1 was detected in
      64.2% of patients, genotype 2 in 18.3%, and genotype 6 in 11.3%. Genotype 1 had a
      significantly lower sustained virologic response rate (32.8%) to interferon
      treatment, compared with genotype 2 (77.8%) or 6 (69.2%). During a mean follow-up
      of 6 yr, 26 patients developed hepatocellular carcinoma (HCC). Logistic
      regression model revealed fibrosis stage 4 (odds ratio [OR] 8.87, 95% confidence
      interval [CI] 2.97-26.48, p < 0.0001), age at presentation (55 vs 35 yr--OR 3.45,
      95% CI 1.22-9.75, p= 0.0194), and baseline albumin level (3.0 vs 4.0 mg/dL--OR
      3.47, 95% CI 1.02-11.76, p= 0.0464) were independent predictive factors for HCC
      development. CONCLUSIONS: Asian Americans with a history of unsafe therapeutic
      injections must be screened for chronic hepatitis C. Antiviral treatment should
      be initiated prior to development of cirrhosis. Surveillance for HCC must be
      routinely performed in cirrhosis patients.

PMID- 17227522
TI  - Liver stiffness measurement versus clinicians' prediction or both for the
      assessment of liver fibrosis in patients with chronic hepatitis C.
AB  - OBJECTIVES: The goal of this study was to estimate the additional value of liver
      stiffness measurement (LSM) with physicians' assessment of fibrosis based on
      epidemiological, clinical, and biological parameters. METHODS: One hundred forty
      two unselected patients with chronic hepatitis C were included. Liver biopsy and
      LSM were performed simultaneously. First, four physicians (two junior residents
      with limited experience in hepatology and two senior hepatologists) independently
      predicted the stage of fibrosis according to the METAVIR classification, using
      clinical, epidemiological, and biological data. For the second step, they were
      informed of LSM values and could modify their first evaluation if necessary.
      Finally, the two successive evaluations were compared with the histological
      fibrosis score. RESULTS: Providing LSM values improved agreement between
      physicians and resulted in a better correlation between clinical impression and
      histological liver fibrosis. The diagnostic performances were only significantly
      improved with transient elastography for the diagnosis of cirrhosis where
      assessment improved in three of the four physicians (AUROC [area under receiver
      operating characteristic curve]: 0.76 vs 0.87, 0.80 vs 0.87, and 0.83 vs 0.89,
      all p < 0.05). Moreover, these performances were nearly similar for junior and
      senior physicians when LSM was provided with the AUROC ranging from 0.69 to 0.72
      for significant fibrosis and 0.87 to 0.90 for cirrhosis. CONCLUSIONS: Providing
      LSM values to physicians results in a better estimation of liver fibrosis and a
      more accurate diagnosis of cirrhosis. Moreover, it allows physicians with limited
      experience to predict liver fibrosis as well as experienced hepatologists.

PMID- 17227523
TI  - Risk factors for clinical phenotypes of Crohn's disease of the ileal pouch.
AB  - BACKGROUND: Crohn's disease (CD) of the pouch can occur in patients with
      colectomy and ileal pouch-anal anastomosis (IPAA) originally performed for a
      preoperative diagnosis of ulcerative colitis. The clinical presentations of CD of
      the pouch are inflammatory, fibrostenotic, and fistulizing. Risk factors for
      clinical phenotypes of CD of the pouch have not been characterized. METHODS: A
      total of 78 eligible patients with CD of the pouch together with 294 nonselected
      non-CD patients with IPAA seen in the Pouchitis Clinic were enrolled, including
      28 with inflammatory CD, 18 with fibrostenotic CD, and 32 with fistulizing CD.
      The clinical phenotypes of CD were diagnosed based on a combined assessment of
      clinical, endoscopic, radiographic, and histologic features. Three separate
      analyses were performed, and for each analysis, the outcome of interest was
      having one of the phenotypes versus not having it. A stepwise selection
      multivariable logistic regression analysis was used. RESULTS: In the
      multivariable analysis, the risk factor for inflammatory CD was higher afferent
      limb endoscopy scores (hazard ratio [HR] 1.87 95% confidence interval [CI] 1.54
      2.27); the risk factors for fibrostenotic CD were higher afferent-limb (95% CI
      1.81-3.48, HR 2.51) and higher cuff (95% CI 1.01-1.84, HR 1.36) endoscopy scores;
      and for fistulizing CD the risk factors were younger age (95% CI 0.93-0.99, HR
      0.96), female gender (95% CI 1.35-6.97, HR 3.07), a preoperative diagnosis of
      indeterminate colitis (95% CI 1.72-9.34, HR 4.00), and no use of nonsteroidal
      antiinflammatory drugs (95% CI 1.31-8.25, HR 3.28). CONCLUSIONS: Each of the
      three phenotypes of CD of the pouch was associated with certain risk factors,
      suggesting that each of these diseases has a different etiology and disease
      process. The identification and management of some of the modifiable risk factors
      may reduce CD-related morbidity.

PMID- 17227524
TI  - Sensitivity disturbances in patients with irritable bowel syndrome and
      fibromyalgia.
AB  - BACKGROUND: Although visceral hypersensitivity is a common feature among patients
      with irritable bowel syndrome (IBS), studies on somatic sensitivity have given
      controversial results. AIM: To assess visceral sensitivity in response to
      isotonic rectal distensions and somatic sensitivity at different layers of the
      body wall (skin, subcutis, and muscle) in patients with IBS and fibromyalgia
      (FM), within and outside the area of abdominal pain referral. MATERIALS AND
      METHODS: We studied 10 patients with IBS, 5 patients with FM, 9 patients with
      IBS+FM, and 9 healthy controls. Rectal distensions were performed by increasing
      tension at 4 g steps up to 64 g or discomfort. Pain thresholds to electrical
      stimulation were measured within and outside the areas of abdominal pain
      referral. RESULTS: Patients with IBS and IBS+FM demonstrated rectal
      hypersensitivity in comparison to controls. The threshold of discomfort was 44 +/
      5 g in IBS and 36 +/- 5 in IBS+FM patients, while patients with FM and healthy
      controls tolerated all distensions without discomfort. In the areas of pain
      referral, pain thresholds of all three tissues of the body wall were lower than
      normal in all patients groups (p < 0.001). In control areas, the pain thresholds
      were normal in skin, and lower than normal in subcutis and muscle in IBS (p <
      0.001). FM and IBS+FM demonstrated somatic hypersensitivity at all sites (p <
      0.001 vs healthy). CONCLUSION: Our observations seem to indicate that, although
      sharing a common hypersensitivity background, multiple mechanisms may modulate
      perceptual somatic and visceral responses in patients with IBS and FM.

PMID- 17227525
TI  - Neostigmine-induced postprandial phasic contractility in the proximal stomach and
      dyspepsia-like symptoms in healthy volunteers.
AB  - BACKGROUND AND AIMS: In a subset of functional dyspepsia patients, we have
      recently described the association between unsuppressed postprandial phasic
      contractions of the proximal stomach and a specific symptom pattern. To better
      elucidate the role of phasic contractility of the proximal stomach in symptom
      generation, we aimed at inducing this motility pattern in healthy volunteers and
      we carefully monitored symptom onset. PATIENTS AND METHODS: Eleven healthy
      volunteers underwent gastric barostat on two separate days. Gastric tone and
      phasic contractility were evaluated for a 90-minute period. In particular, after
      30 min of basal recording, a caloric liquid meal and neostigmine 0.5 mg IV or
      saline in a double-blind, randomized, crossover protocol were administered.
      During the measurement, severity of 9 dyspeptic symptoms was evaluated on a
      visual analog scale. Computer-aided baseline reconstruction allowed us to
      quantify phasic contractions as a motility index (MI), reflecting the area
      between signal and baseline normalized over time. Perception of contractions
      after placebo or neostigmine was evaluated. Moreover, we tested for influence of
      gastric tone and phasic contractility on symptoms. RESULTS: After neostigmine,
      gastric accommodation was not different than after placebo (225 +/- 36 vs 206 +/-
      76 mL, P= NS). During the first 30-min postprandial period, the MI was
      significantly higher after neostigmine than after placebo (26.4 +/- 3 vs 21.4 +/-
      3, P < 0.001), confirming the induction of unsuppressed postprandial phasic
      contractions. The postprandial total symptom score was significantly higher after
      neostigmine compared to saline; several individual postprandial symptom scores
      were also significantly higher after neostigmine-compared placebo. After
      neostigmine, a higher percentage of postprandial contractions was perceived
      compared to placebo. CONCLUSIONS: Unsuppressed postprandial phasic contractility
      of the proximal stomach is a mechanism potentially involved in the pathogenesis
      of dyspeptic symptoms.

PMID- 17227526
TI  - Optical coherence tomography evaluation of ulcerative colitis: the patterns and
      the comparison with histology.
AB  - HYPOTHESIS: The optical coherence tomography (OCT) is an imaging modality based
      on infrared light backscattering properties of tissues. OCT studies documented
      the disappearance of crypts and the alteration in light backscattering as
      features of ulcerative colitis (UC) in human colon. This technique should be more
      and more able to identify tissue microstructures with a resolution that is nearly
      that of histology (optical biopsy). AIM: To evaluate whether there are OCT
      patterns specific for UC and to compare the overall technique performance with
      the histology. METHODS: A total of 27 patients (20-76 yr) with UC underwent OCT
      imaging during a total colonoscopy. The OCT images were collected both from
      affected and normal sites in active UC or disease in remission. Two biopsies of
      the same sites were acquired. The OCT images were separately scored. Two
      pathologists blinded to the endoscopic and OCT patterns scored the samples.
      RESULTS: Three OCT patterns were identified: the mucosal backscattering
      alteration (MBA), the delimited dark areas (DDA), and the layered colonic wall
      (LCW). In colon affected segments of active and UC in remission, these patterns
      showed a good correspondence with the histology. Moreover, in 14/25 (56%) normal
      sites above the affected segment, the OCT documented the pathological features,
      confirmed only in 10/14 by the histology. Thus, the assessed sensitivity and
      specificity of OCT in normal segments of UC patients have been 100% and 69%,
      respectively. CONCLUSIONS: The in vivo OCT correctly detected disease features in
      endoscopically affected colon segments, but even in apparently normal segments of
      UC patients.

PMID- 17227527
TI  - Maximizing detection of adenomas and cancers during colonoscopy.
AB  - Some patients who undergo colonoscopy that appeared to have cleared the
      colorectum of neoplasia return within a short interval (1-3 yr) with colorectal
      cancer. Although several a priori mechanisms could account for this occurrence,
      wide variation in detection rates of adenomas and cancer at colonoscopy suggests
      that suboptimal colonoscopic technique is a significant contributor. Optimal
      technique with white-light colonoscopy involves taking adequate time for
      inspection during withdrawal (an average of at least 6 min in normal colons),
      interrogating the proximal sides of folds, flexures, and valves, clearing fluid
      and debris, and distending adequately. Some adjunctive techniques are directed
      toward exposing more colonic mucosa during colonoscopy. Wide-angle colonoscopy
      appears to improve efficiency but does not eliminate miss rates. Colonoscopy in
      retroflexion was unsuccessful in reducing miss rates in one study, whereas cap
      fitted colonoscopy was successful in reducing miss rates in one small study.
      Techniques to improve detection of flat lesions include pancolonic
      chromoendoscopy (CE). In two randomized controlled trials, CE improved adenoma
      detection, but CE does not appear to provide substantially greater yields than
      those obtained by the more sensitive white-light colonoscopists. Narrow band
      imaging and autofluorescence are being assessed for improved detection of flat
      lesions. Adenoma detection rates are an important measure of the quality of
      colonoscopy and should be reported to endoscopists in quality improvement
      programs in colonoscopy.

PMID- 17227528
TI  - Adequate relief in IBS treatment trials: corrections to errors stated by
      Whitehead et al.

PMID- 17227531
TI  - Endoscopic ultrasound in esophageal cancer staging.

PMID- 17227532
TI  - Continuous infusion or repeated intravenous bolus injection of high-dose
      omeprazole in patients at high risk of rebleeding from peptic ulcers?

PMID- 17227534
TI  - Response: Double blind trial in Crohn's disease of autologous colon extracted
      proteins Am J Gastroenterol 2006;101:561-8.

PMID- 17227538
TI  - Endoscopic clipping can be dangerous.

PMID- 17227539
TI  - Factors associated with the development of intestinal strictures or obstructions
      in patients with Crohn's disease.

PMID- 17227540
TI  - Successful paternity of a healthy child while taking methotrexate for Crohn's
      disease.

PMID- 17227544
TI  - Isolation and characterization of the RAD54 gene from Arabidopsis thaliana.
AB  - Homologous recombination (HR) is an essential process in maintaining genome
      integrity and variability. In eukaryotes, the Rad52 epistasis group proteins are
      involved in meiotic recombination and/or HR repair. One member of this group,
      Rad54, belongs to the SWI2/SNF2 family of DNA-stimulated ATPases. Recent studies
      indicate that Rad54 has important functions in HR, both as a chromatin
      remodelling factor and as a mediator of the Rad51 nucleoprotein filament. Despite
      the importance of Rad54 in HR, no study of Rad54 from plants has yet been
      performed. Here, we cloned the full-length AtRAD54 cDNA sequence; an open reading
      frame of 910 amino acids encodes a protein with a predicted molecular mass of
      101.9 kDa. Western blotting analysis showed that the AtRad54 protein was indeed
      expressed as a protein of approximately 110 kDa in Arabidopsis. The predicted
      protein sequence of AtRAD54 contains seven helicase domains, which are conserved
      in all other Rad54s. Yeast two-hybrid analysis revealed an interaction between
      Arabidopsis Rad51 and Rad54. AtRAD54 transcripts were found in all tissues
      examined, with the highest levels of expression in flower buds. Expression of
      AtRAD54 was induced by gamma-irradiation. A T-DNA insertion mutant of AtRAD54
      devoid of full-length AtRAD54 expression was viable and fertile; however, it
      showed increased sensitivity to gamma-irradiation and the cross-linking reagent
      cisplatin. In addition, the efficiency of somatic HR in the mutant plants was
      reduced relative to that in wild-type plants. Our findings point to an important
      role for Rad54 in HR repair in higher plants.

PMID- 17227545
TI  - Analysis of calcium spiking using a cameleon calcium sensor reveals that
      nodulation gene expression is regulated by calcium spike number and the
      developmental status of the cell.
AB  - Rhizobium-made Nod factors induce rapid changes in both Ca(2+) and gene
      expression. Mutations and inhibitors that abolish Nod-factor-induced Ca(2+)
      spiking block gene induction, indicating a specific role for Ca(2+) spiking in
      signal transduction. We used transgenic Medicago truncatula expressing a
      "cameleon" Ca(2+) sensor to assess the relationship between Nod-factor-induced
      Ca(2+) spiking and the activation of downstream gene expression. In contrast to
      ENOD11 induction, Ca(2+) spiking is activated in all root-hair cells and in
      epidermal or pre-emergent root hairs cells in the root tip region. Furthermore,
      cortical cells immediately below the epidermal layer also show slow Ca(2+)
      spiking and these cells lack Nod-factor-induced ENOD11 expression. This indicates
      a specialization in nodulation gene induction downstream of Nod-factor perception
      and signal transduction. There was a gradient in the frequency of Ca(2+) spiking
      along the root, with younger root-hair cells having a longer period between
      spikes than older root hairs. Using a Ca(2+)-pump inhibitor to block Ca(2+)
      spiking at various times after addition of Nod factor, we conclude that about 36
      consecutive Ca(2+) spikes are sufficient to induce ENOD11-GUS expression in root
      hairs. To determine if the length of time of Ca(2+) spiking or the number of
      Ca(2+) spikes is more critical for Nod-factor-induced ENOD11 expression, jasmonic
      acid (JA) was added to reduce the rate of Nod-factor-induced Ca(2+) spiking. This
      revealed that even when the period between Ca(2+) spikes was extended, an
      equivalent number of Ca(2+) spikes were required for the induction of ENOD11.
      However, this JA treatment did not affect the spatial patterning of ENOD11-GUS
      expression suggesting that although a minimal number of Ca(2+) spikes are
      required for Nod-factor-induced gene expression, other factors restrict the
      expression of ENOD11 to a subset of responding cells.

PMID- 17227546
TI  - Comparative genomics and repetitive sequence divergence in the species of diploid
      Nicotiana section Alatae.
AB  - Combining phylogenetic reconstructions of species relationships with comparative
      genomic approaches is a powerful way to decipher evolutionary events associated
      with genome divergence. Here, we reconstruct the history of karyotype and tandem
      repeat evolution in species of diploid Nicotiana section Alatae. By analysis of
      plastid DNA, we resolved two clades with high bootstrap support, one containing
      N. alata, N. langsdorffii, N. forgetiana and N. bonariensis (called the n = 9
      group) and another containing N. plumbaginifolia and N. longiflora (called the n
      = 10 group). Despite little plastid DNA sequence divergence, we observed, via
      fluorescent in situ hybridization, substantial chromosomal repatterning,
      including altered chromosome numbers, structure and distribution of repeats.
      Effort was focussed on 35S and 5S nuclear ribosomal DNA (rDNA) and the HRS60
      satellite family of tandem repeats comprising the elements HRS60, NP3R and NP4R.
      We compared divergence of these repeats in diploids and polyploids of Nicotiana.
      There are dramatic shifts in the distribution of the satellite repeats and
      complete replacement of intergenic spacers (IGSs) of 35S rDNA associated with
      divergence of the species in section Alatae. We suggest that sequence
      homogenization has replaced HRS60 family repeats at sub-telomeric regions, but
      that this process may not occur, or occurs more slowly, when the repeats are
      found at intercalary locations. Sequence homogenization acts more rapidly (at
      least two orders of magnitude) on 35S rDNA than 5S rDNA and sub-telomeric
      satellite sequences. This rapid rate of divergence is analogous to that found in
      polyploid species, and is therefore, in plants, not only associated with
      polyploidy.

PMID- 17227547
TI  - A mutation in Arabidopsis cytochrome b5 reductase identified by high-throughput
      screening differentially affects hydroxylation and desaturation.
AB  - As a model for analyzing the production of novel fatty acids in oilseeds, we used
      the genetic and molecular techniques available for Arabidopsis to characterize
      modifying mutations affecting the accumulation of hydroxy fatty acids in the
      seeds of Arabidopsis plants that express a transgene for the castor bean fatty
      acid hydroxylase, FAH12. We developed a high-throughput analytical system and
      used it to identify three complementation classes of mutations with reduced
      hydroxy fatty acid accumulation from among Arabidopsis M3 seed samples derived
      from chemical mutagenesis. We identified one of the mutations by positional
      cloning as a single base pair change in a gene encoding NADH:cytochrome b5
      reductase (CBR1, At5g17770). When expressed in yeast, the mutant form of the
      enzyme was less active and less stable than the wild-type enzyme.
      Characterization of homozygous mutant lines with and without the FAH12 transgene
      (FAH12 cbr1-1 and cbr1-1, respectively) indicated that the only detectable
      consequence of the cbr1-1 mutation was on desaturase and hydroxylase reactions in
      the developing seed. The leaf and root fatty compositions, as well as the growth,
      development and seed production of mutant plants were indistinguishable from wild
      type. Interestingly, while the cbr1-1 mutation reduced the accumulation of
      hydroxy fatty acids in seeds by 85%, the effects on 18:1 and 18:2 desaturation
      reactions were much less (<25% and <60%, respectively). These results suggest
      that there is competition in developing seeds among the several reactions that
      utilize reduced cytochrome b5.

PMID- 17227548
TI  - PDX1 is essential for vitamin B6 biosynthesis, development and stress tolerance
      in Arabidopsis.
AB  - Vitamin B6 is an essential coenzyme for numerous metabolic enzymes and is a
      potent antioxidant. In plants, very little is known about its contribution to
      viability, growth and development. The de novo pathway of vitamin B6 biosynthesis
      has only been described recently and involves the protein PDX1 (pyridoxal
      phosphate synthase protein). Arabidopsis thaliana has three homologs of PDX1, two
      of which, PDX1.1 and PDX1.3, have been demonstrated as functional in vitamin B6
      biosynthesis in vitro and by yeast complementation. In this study, we show that
      the spatial and temporal expression patterns of PDX1.1 and PDX1.3, investigated
      at the transcript and protein level, largely overlap, but PDX1.3 is more abundant
      than PDX1.1. Development of single pdx1.1 and pdx1.3 mutants is partially
      affected, whereas disruption of both genes causes embryo lethality at the
      globular stage. Detailed examination of the single mutants, in addition to those
      that only have a single functional copy of either gene, indicates that although
      these genes are partially redundant in vitamin B6 synthesis, PDX1.3 is more
      requisite than PDX1.1. Developmental distinctions correlate with the vitamin B6
      content. Furthermore, we provide evidence that in addition to being essential for
      plant growth and development, vitamin B6 also plays a role in stress tolerance
      and photoprotection of plants.

PMID- 17227549
TI  - ATR and ATM play both distinct and additive roles in response to ionizing
      radiation.
AB  - The ATR and ATM protein kinases are known to be involved in a wide variety of
      responses to DNA damage. The Arabidopsis thaliana genome includes both ATR and
      ATM orthologs, and plants with null alleles of these genes are viable.
      Arabidopsis atr and atm mutants display hypersensitivity to gamma-irradiation. To
      further characterize the roles of ATM and ATR in response to ionizing radiation,
      we performed a short-term global transcription analysis in wild-type and mutant
      lines. We found that hundreds of genes are upregulated in response to gamma
      irradiation, and that the induction of virtually all of these genes is dependent
      on ATM, but not ATR. The transcript of CYCB1;1 is unique among the cyclin
      transcripts in being rapidly and powerfully upregulated in response to ionizing
      radiation, while other G(2)-associated transcripts are suppressed. We found that
      both ATM and ATR contribute to the induction of a CYCB1;1:GUS fusion by IR, but
      only ATR is required for the persistence of this response. We propose that this
      upregulation of CYCB1;1 does not reflect the accumulation of cells in G(2), but
      instead reflects a still unknown role for this cyclin in DNA damage response.

PMID- 17227550
TI  - Time of day modulates low-temperature Ca signals in Arabidopsis.
AB  - We tested the hypothesis that the circadian clock modulates Ca(2+)-based
      signalling pathways, using low-temperature (LT)-induced Ca(2+) signals. We
      investigated the relationship between diurnal and circadian modulation of LT
      induced increases in cytosolic-free calcium ([Ca(2+)](cyt)), and regulation of
      [Ca(2+)](cyt)-dependent outputs of the LT-signalling network (RD29A transcript
      abundance and stomatal closure). We measured [Ca(2+)](cyt) non-invasively using
      aequorin, and targeted aequorin to the guard cell using a guard cell-specific
      GAL4-green fluorescent protein enhancer trap line. LT caused transient increases
      in whole plant and guard cell [Ca(2+)](cyt). In guard cells, the LT-induced
      [Ca(2+)](cyt) elevation preceded stomatal closure. In whole plants, the magnitude
      of LT-induced [Ca(2+)](cyt) transients, measured from the entire plant or
      specifically the guard cell, varied with the time of day: LT-induced
      [Ca(2+)](cyt) transients were significantly higher during the mid-photoperiod
      than at the beginning or end. Diurnal variation in LT-induced guard cell
      [Ca(2+)](cyt) increases was not correlated to diurnal variation in LT-induced
      stomatal closure. There was circadian modulation of LT-induced whole plant
      [Ca(2+)](cyt) increases, which were correlated to the circadian pattern of RD29A
      induction. In order to understand the significance of LT-induced [Ca(2+)](cyt)
      increases, we used a computer simulation to demonstrate that, in guard cells, LT
      induced [Ca(2+)](cyt) increases measured from a population of cells are likely to
      represent the summation of cold-induced single-cell [Ca(2+)](cyt) oscillations.

PMID- 17227551
TI  - The FOX hunting system: an alternative gain-of-function gene hunting technique.
AB  - We have developed a novel gain-of-function system that we have named the FOX
      hunting system (Full-length cDNA Over-eXpressing gene hunting system). We used
      normalized full-length cDNA and introduced each cDNA into Arabidopsis by in
      planta transformation. About 10 000 independent full-length Arabidopsis cDNAs
      were expressed independently under the CaMV 35S promoter in Arabidopsis. Each
      transgenic Arabidopsis contained on average 2.6 cDNA clones and was monitored
      under various categories such as morphological changes, fertility and leaf color.
      We found 1487 possible morphological mutants from 15 547 transformants. When 115
      pale green T(1) mutants were analyzed, 59 lines represented the mutant phenotypes
      in more than 50% of the T(2) progeny. Characterization of two leaf color mutants
      revealed the significance of this approach. We also document mutants from several
      categories and their corresponding full-length cDNAs.

PMID- 17227552
TI  - Alloimmunity: no toll exemption.

PMID- 17227553
TI  - Gal knockout and beyond.
AB  - Recently, Galalpha1-3Galbeta1-4GlcNAc (Gal) knockout (k/o) pigs have been
      developed using genetic cloning technologies. This remarkable achievement has
      generated great enthusiasm in xenotransplantation studies. This review summarizes
      the current status of nonhuman primate experiments using Gal k/o pig organs.
      Briefly, when Gal k/o pig organs are transplanted into primates, hyperacute
      rejection does not occur. Although graft survival has been prolonged up to a few
      months in some cases, the overall results were not better than those using Gal
      positive pig organs with human complement regulatory protein transgenes. Gal k/o
      pig kidneys rapidly developed rejection which was associated with increased anti
      non-Gal antibodies. Although the precise mechanisms of Gal k/o pig organ
      rejection are not clear, it could result from incomplete deletion of Gal, up
      regulation of new antigen (non-Gal antigen) and/or production of non-Gal
      antibodies. Future work in xenotransplantation should place emphasis on further
      modification of donors, such as combining human complement regulatory genes with
      Gal k/o, deleting non-Gal antigens and adding protective/surviving genes or a
      gene that inhibits coagulation. Induction of donor-specific T- and B-cell
      tolerance and promotion of accommodation are also warranted.

PMID- 17227555
TI  - Anti-CD45RB monoclonal antibody prolongs renal allograft survival in cynomolgus
      monkeys.
AB  - Previously, an anti-CD45RB monoclonal antibody (mAb) has been shown to induce
      murine allograft tolerance. The present study was performed to assess the ability
      of an anti-human CD45RB mAb to prevent rejection in a monkey MHC-mismatched
      kidney transplant model. The recipients were allocated into the following
      treatment groups: (1) isotype control IgG; (2) mouse anti-human CD45RB IgG1
      (6G3); (3) human-mouse chimeric anti-CD45RB-IgG1 (C6G3-IgG1); (4) human-mouse
      chimeric anti-CD45RB-IgG2 (C6G3-IgG2); (5) tacrolimus at a subtherapeutic dose
      and (6) tacrolimus and C6G3-IgG1 in combination. Monotherapy with anti-CD45RB mAb
      significantly prolonged renal allograft survival to a median survival of 21 days.
      Adding a subtherapeutic dose of tacrolimus improved the efficacy of the anti
      CD45RB mAb, achieving a median survival of 85 days, whereas a subtherapeutic dose
      of tacrolimus alone only moderately prolonged survival to 27 days. Treatment with
      anti-CD45RB mAb resulted in an alteration of the CD45RB(hi) : CD45RB(lo) cell
      ratio in the peripheral blood. We have, for the first time, demonstrated that an
      anti-human CD45RB mAb (6G3) can prolong graft survival. Induction with an anti
      CD45RB mAb improves the efficacy of tacrolimus in the prevention of rejection.
      These encouraging results indicate that an anti-CD45RB mAb may be valuable in
      future clinical transplantation.

PMID- 17227556
TI  - Quantification of basal and stimulated ROS levels as predictors of islet potency
      and function.
AB  - We have developed a luminol-based assay using intact islets, which allows for
      quantification of reactive oxygen species (ROS). In addition, an index capable of
      characterizing metabolic and mitochondrial integrity prior to transplantation was
      created based on the capacity of islets to respond to high glucose and rotenone
      (mitochondrial respiratory chain complex I inhibitor) by production of ROS. To
      validate this assay, lipid peroxidation and antioxidative defense capacity were
      evaluated by detection of malondialdehyde (MDA) levels and glutathione peroxidase
      activity (GPx), respectively. Also, flow cytometric analyses of ROS
      (dihydroethidine), apoptosis (Annexin V, active caspases), necrosis (Topro3), and
      mitochondrial membrane potential (JC-1) were done in parallel to correlate with
      changes in luminol-measured ROS. ATP/ADP ratios were quantified by HPLC and the
      predictive value of ROS measurement on islet functional potency was correlated
      with capacity to reverse diabetes in a streptozotocin-induced diabetic NOD.scid
      mouse model as well as in human transplant recipients. Our data demonstrate that
      levels of ROS in islets correlate with the percentage of apoptotic cells and
      their functional potency in vivo. The ROS indices following glucose and rotenone
      exposure are indicative of metabolic potency and mitochondrial integrity and can
      be used as surrogate markers to evaluate the quality of islets prior to
      transplantation.

PMID- 17227557
TI  - Sirolimus improves early microcirculation, but impairs regeneration after
      pancreatic ischemia-reperfusion injury.
AB  - Ischemia and reperfusion injury remains a relevant problem in clinical pancreas
      transplantation. We investigated the effect of sirolimus (SRL) in a rodent model
      of 90-min warm pancreatic ischemia. Four groups were studied: (1) sham surgery
      and vehicle; (2) sham surgery and SRL; (3) warm ischemia and vehicle; (4) warm
      ischemia and SRL. SRL (1.5 mg/kg/day) and vehicle were administered
      intraperitoneally for 3 days prior to surgery until the animals were killed.
      Microcirculation was assessed immediately after reperfusion by means of
      intravital fluorescence microscopy. Histopathological injury, apoptosis,
      proliferation and biochemical parameters were analyzed at 2 h, 1 day and 5 days
      after surgery. Ninety minutes after ischemia, intravital microscopy revealed an
      improved functional capillary density (p < 0.05) and reduction of adherent
      leucocytes (p < 0.01) and platelets (p < 0.05) in the SRL-treated group compared
      to the vehicle-treated controls. In contrast, on day 5 after ischemia, the
      pancreatic tissue of SRL-treated animals showed a higher grade of histological
      injury (p < 0.05) and higher rate of apoptotic cells (p < 0.05) than the vehicle
      controls. In summary, our data indicate that administration of SRL improves
      microcirculation at a very early stage, but results in an impairment of the
      recovery phase after pancreatic ischemia-reperfusion injury.

PMID- 17227558
TI  - Chronic cardiac transplant arteriopathy in mice: relationship of alloantibody,
      C4d deposition and neointimal fibrosis.
AB  - Murine heterotopic cardiac allografts were used to reveal some of the fundamental
      interrelationships between donor-specific alloantibodies (DSA), chronic
      transplant arteriopathy (CTA) and capillary C4d deposition. B10.BR recipients of
      B10.A hearts developed transient DSA and C4d deposition that peaked on day 7 and
      became undetectable at day 56 while CTA developed progressively. Male cardiac
      grafts in female recipients showed similar degrees of CTA at day 56 but never
      developed DSA or C4d deposition, indicating that T cell-mediated mechanisms are
      sufficient to produce CTA. Passive transfer of monoclonal IgG2a anti-H-2K(k) into
      B6.RAG1 KO recipients of B10.BR hearts over 14-28 days led to progressive CTA. If
      treatment was stopped on day 14, lesions showed little progression and had no C4d
      deposition or detectable DSA on day 42. If treatment was stopped on day 28 when
      the lesions were fully developed, no regression occurred over the next 28 days,
      even though C4d deposition and circulating antibody became undetectable.
      Therefore, a minimum threshold of antibody exposure is needed to cause CTA. Once
      the CTA develops, C4d may become negative after DSA disappears. Thus, serial
      samples are needed in clinical studies to ascertain the relevance of alloantibody
      to the lesions of chronic graft rejection.

PMID- 17227559
TI  - Early hemodynamic injury during donor brain death determines the severity of
      primary graft dysfunction after lung transplantation.
AB  - Sympathetic discharge and hypertensive crisis often accompany brain death,
      causing neurogenic pulmonary edema. Progressive systemic inflammatory response
      develops, which can injure the lung further. We investigated whether (a) early
      hemodynamic injury during donor brain death increases reperfusion injury after
      lung transplantation and (b) delaying lung recovery would augment reperfusion
      injury further, because of the progressive systemic inflammatory response in the
      donor. Brain death was induced by intracranial balloon inflation in rats, with or
      without alpha-adrenergic blockade pretreatment to prevent the hypertensive
      crisis. Another group of rats had a sham procedure. Lungs were retrieved 15 min
      after brain death or sham procedure and reperfused using recipient rats. In a
      fourth group, brain death was induced and the lungs were retrieved 5 h after
      brain death and reperfused. Postreperfusion, lungs retrieved early from untreated
      brain-dead donors developed more severe reperfusion injury, as assessed by
      functional parameters and inflammatory markers, than those from sham or alpha
      blockade-treated donors. Lungs retrieved late from brain-dead donors had similar
      inflammatory markers after reperfusion to those retrieved early, but
      significantly lower pulmonary vascular resistance. Early hemodynamic damage
      during donor brain death increases reperfusion injury after lung transplantation.
      Delaying retrieval may allow the lung to recover from the hemodynamic injury.

PMID- 17227560
TI  - Changes in renal function after clinical islet transplantation: four-year
      observational study.
AB  - Tight glycemic control can reduce progression of diabetic nephropathy (DN) while
      the histological changes may regress after pancreas transplantation. Clinical
      islet transplantation (CIT) can restore euglycemia but the effects of CIT and
      concomitant immunosuppression on renal function are not known. Renal function
      (modification of diet in renal disease estimated glomerular filtration rate
      [GFR]) is reported in 41 type 1 diabetes subjects followed for 29.8 (6-57) months
      after CIT who received sirolimus and tacrolimus. HbA(1c) improved by 3 months
      (6.1 +/- 0.5 vs. 8.1 +/- 1.3%, p < 0.001) and was sustained. Over 4 years
      estimated GFR (eGFR) declined (repeated measures ANOVA: p = 0.0011). The median
      rate of change in eGFR was -0.39 mL/min/1.73 m(2)/month but was highly variable
      (range: +1.62 to -2.79 mL/min/1.73 m(2)/month). Progression of albuminuria was
      observed in ten individuals while regression of microalbuminuria was observed in
      only one (chi square = 22.51, df = 4, p = 0.0002). Despite improved glycemia, CIT
      and concomitant immunosuppression, was associated with a fall in eGFR and
      progression of albuminuria over 4 years of observation. The rate of decline in
      eGFR was extremely variable and difficult to predict. The risk of progressive
      nephrotoxicity with decline in eGFR should be discussed with prospective CIT
      candidates and the risk: benefit ratio carefully considered in individuals with
      pre-existing renal impairment.

PMID- 17227561
TI  - Cold ischemia time and allograft outcomes in live donor renal transplantation: is
      live donor organ transport feasible?
AB  - One of the greatest obstacles to the implementation of regional or national
      kidney paired donation programs (KPD) is the need for the donor to travel to
      their matched recipient's hospital. While transport of the kidney is an
      attractive alternative, there is concern that prolonged cold ischemia time (CIT)
      would diminish the benefits of live donor transplantation (LDTx). To examine the
      impact of increased CIT in LDTx, 1-year serum creatinine (SCr), delayed graft
      function (DGF), acute rejection (AR) and allograft survival (AS) were analyzed in
      38 467 patients by 2 h CIT groups (0-2, 2-4, 4-6 and 6-8 h) using data from the
      United Network for Organ Sharing/Organ Procurement and Transplantation Network
      (UNOS/OPTN). Adjusted probabilities of DGF and AR were estimated in multivariate
      logistic regression models and AS was examined in multivariate Cox proportional
      hazards models. Although some increase in DGF was observed between the 0-2 h
      (4.7%) and 4-6 h (8.3%) groups, prolonged CIT did not result in inferior SCr,
      increased AR or compromised AS in any group with >2 h CIT compared with the 0-2 h
      group. Comparable long-term outcomes for these grafts suggests that transport of
      live donor organs may be a feasible alternative to donor travel in KPD regions
      where CIT can be limited to 8 h.

PMID- 17227562
TI  - Successful combined partial auxiliary liver and kidney transplantation in highly
      sensitized cross-match positive recipients.
AB  - Combined liver and renal transplantations can be performed against a positive
      cross-match, indicating that the liver protects the kidney from the harmful HLA
      antibodies. This led us to the hypothesis that a partial auxiliary liver graft
      may have a similar protective effect when performed together with the kidney in
      highly sensitized patients. Seven patients, with broadly reacting HLA antibodies
      and positive crossmatches, were transplanted with a partial liver and a kidney
      from the same donor. In one of the cases a living donor was used. We performed
      lymphocytotoxic and flow cross-matches before and after the transplantation.
      Cross-matches turned negative after grafting in five of seven cases. The kidney
      function was excellent, without rejections, during the follow-up (24-60 months)
      in these patients. In two cases the cross-match remained positive after
      transplantation, one with a never-functioning renal graft and the other with an
      early graft failure, probably due to humoral rejection. A simultaneous
      transplantation of a partial auxiliary liver graft from the same donor, with the
      sole purpose of protecting the kidney from harmful lymphocytotoxic antibodies,
      can be performed successfully despite a positive cross-match and may thus be a
      new option of treatment for highly sensitized patients waiting for a kidney
      transplant.

PMID- 17227563
TI  - Selective use of older adults in right lobe living donor liver transplantation.
AB  - Many centers are reluctant to use older donors (>44 years) for adult right-lobe
      living donor liver transplantation (RLDLT) due to concerns about possible
      increased morbidity in donors and poorer outcomes in recipients. Since 2000, 130
      adult RLDLTs have been performed at our institution. Recipients were divided into
      those who received a right lobe graft from a donor </=age 44 (n = 89, 68%; median
      age 30) and those who received a liver graft from a donor age >44 (n = 41, 32%;
      mean age 52). The two donor and recipient populations had similar demographic and
      operative profiles. With a median follow-up of 29 months, the severity and number
      of complications in older donors were similar to those in younger donors. No
      living donor died. Older donor allografts had initial allograft dysfunction
      compared to younger donors. Complication rates were similar among recipients in
      both groups but there was a higher bile duct stricture rate with older donor
      grafts (27% vs. 12%; p = 0.04). One-year recipient graft survival was 86% for
      older donors and 85% for younger donors (p = 0.95). Early experience with the use
      of selected older adults (>44 years) for RLDLT is encouraging, but may be
      associated with a higher rate of biliary complications in the recipient.

PMID- 17227564
TI  - Nontransplantation of livers from deceased donors who are able to donate another
      solid organ: how often and why it happens.
AB  - Deceased donor factors associated with poor graft outcome are well known, but how
      often these factors lead to livers left untransplanted is poorly defined. A
      nested, case-control study was conducted using the United Network for Organ
      Sharing (UNOS) database from 1987 to 2005. Only those donating >/=1 solid organ
      were included. Primary outcome was livers not transplanted (LNT, cases) versus
      transplanted (LT, controls). Primary variables for multivariate analysis were
      donor age and obesity. Covariates included donation after cardiac death (DCD),
      cerebral vascular accident death, viral serologies, cancer, ALT and bilirubin.
      There were 23 373 (26%) LNT's from 91 362 donors who donated at least one organ.
      Percent LNT fell over time (1987-1990: 48%; 1991-1995: 29%; 1996-2000: 21%; 2000
      2005: 16%; p < 0.01). Increased age (odds ratio: 4.2, 95% confidence interval 3.6
      4.9, p < 0.01) and obesity (2.1, 1.9-2.3, p < 0.01) were significantly associated
      with LNT across all time periods. Other significant factors included DCD and
      elevated ALT. For 2001-2005, population attributable risk indicate that age >40,
      abnormal ALT and obesity account for 32.6%, 25.3% and 9.2% of untransplanted
      livers, respectively. Use of expanded criteria livers has pushed LNT lower in
      spite of an aging and heavier donor population. Nevertheless, age and obesity
      still account for a significant portion of untransplanted livers.

PMID- 17227565
TI  - Biliary strictures in 130 consecutive right lobe living donor liver transplant
      recipients: results of a Western center.
AB  - Biliary strictures remain the most challenging aspect of adult right lobe living
      donor liver transplantation (RLDLT). Between 04/2000 and 10/2005, 130 consecutive
      RLDLTs were performed in our center and followed prospectively. Median follow-up
      was 23 months (range 3-67) and 1-year graft and patient survival was 85% and 87%,
      respectively. Overall incidence of biliary leaks (n = 19) or strictures (n = 22)
      was 32% (41/128) in 33 patients (26%). A duct-to-duct (D-D) or Roux-en-Y (R-Y)
      anastomosis were performed equally (n = 64 each) with no difference in stricture
      rate (p = 0.31). The use of ductoplasty increased the number of grafts with a
      single duct for anastomosis and reduced the biliary complication rate compared to
      grafts >/=2 ducts (17% vs. 46%; p = 0.02). Independent risk factors for
      strictures included older donor age and previous history of a bile leak. All
      strictures were managed nonsurgically initially but four patients ultimately
      required conversion from D-D to R-Y. Ninety-six percent (123/128) of patients are
      currently free of any biliary complications. D-D anastomosis is safe after RLDLT
      and provides access for future endoscopic therapy in cases of leak or stricture.
      When presented with multiple bile ducts, ductoplasty should be considered to
      reduce the potential chance of stricture.

PMID- 17227566
TI  - Rejection under alpha interferon therapy in liver transplant recipients.
AB  - Interferon alpha (IFN) is the corner stone drug for the treatment of recurrent
      hepatitis C (HCV) in liver transplant (LT) recipients. One of its serious
      potential adverse effects is acute and chronic rejection. The aim of this study
      was to review our experience using IFN-based therapy, in order to examine the
      incidence and the risk factors for rejection, and the outcome of patients who
      developed rejection. Between September 1990 and December 2004, 70 LT recipients
      were treated. Patients started antiviral treatment 16 (1-137) months after LT.
      Histological follow-up was available in all patients according to protocol
      biopsies. Rejection was diagnosed and graded according to Banff classification.
      Twenty-one percent of patients developed acute rejection (5 mild, 9 moderate and
      1 severe) during IFN-based therapy. Patients were treated for 8 (1-15) months
      prior to rejection. Previous history of acute rejection before IFN therapy and
      treatment with pegylated-IFN was significantly associated with rejection (p =
      0.04 and p = 0.02, respectively). The rejection was successfully treated in 87%
      of patients. No chronic rejection or graft losses were observed. Acute rejection
      under IFN-based therapy often occurs in LT recipients, but early diagnosis with
      protocol biopsies and early treatment can lead to a favorable outcome.

PMID- 17227567
TI  - Efficacy and safety of antifibrinolytic drugs in liver transplantation: a
      systematic review and meta-analysis.
AB  - Although several randomized controlled trials (RCTs) have shown the efficacy of
      antifibrinolytic drugs in liver transplantation, their use remains debated due to
      concern for thromboembolic complications. None of the reported RCTs has shown a
      higher incidence of these complications in treated patients; however, none of the
      individual studies has been large enough to elucidate this issue completely. We
      therefore performed a systematic review and meta-analysis of efficacy and safety
      endpoints in all published controlled clinical trials on the use of
      antifibrinolytic drugs in liver transplantation. Studies were included if
      antifibrinolytic drugs (epsilon-aminocaproic acid, tranexamic acid (TA) or
      aprotinin) were compared with each other or with controls/placebo. Intraoperative
      red blood cell and fresh frozen plasma requirements, the perioperative incidence
      of hepatic artery thrombosis, venous thromboembolic events and mortality were
      analyzed. We identified 23 studies with a total of 1407 patients which met the
      inclusion criteria. Aprotinin and TA both reduced transfusion requirements
      compared with controls. No increased risk for hepatic artery thrombosis, venous
      thromboembolic events or perioperative mortality was observed for any of the
      investigated drugs. This systematic review and meta-analysis does not provide
      evidence for an increased risk of thromboembolic events associated with
      antifibrinolytic drugs in liver transplantation.

PMID- 17227568
TI  - Active immunization to prevent de novo hepatitis B virus infection in pediatric
      live donor liver recipients.
AB  - This study aims to evaluate the efficacy of HBV vaccination as an alternative
      preventive measure against de novo HBV infection in pediatric living donor liver
      transplantation (LDLT). Sixty recipients were enrolled in this study. Thirty
      received grafts from anti-HBc(+) donors, and another 30 received grafts from anti
      HBc(-) donors. HBV vaccine was given pretransplant to every candidate.
      Posttransplant, lamivudine was routinely given to recipients receiving anti
      HBc(+) grafts for about 2 years. Forty-seven (78%) recipients achieved high
      levels of anti-HBs titer (>1000 IU/L). Two (3.3%) recipients developed de novo
      HBV infection where one received an anti-HBc(-) graft and another received an
      anti-HBc(+) graft. Both recipients were in the lower anti-HBs titer group (<1000
      IU/L). The incidence of de novo HBV infection was significantly higher in the
      lower titer group (15.4% vs. 0%, p = 0.04). The median follow-up period was 51
      months in recipients with anti-HBc(-) grafts and 57 months in those with anti
      HBc(+) grafts. Active immunization is an effective method to prevent de novo HBV
      infection. It can result in high levels of anti-HBs titer (>1000 IU/L) which may
      prevent de novo HBV infection in pediatric patients with efficient primary
      vaccination undergoing LDLT.

PMID- 17227569
TI  - Traumatic memories of relatives regarding brain death, request for organ donation
      and interactions with professionals in the ICU.
AB  - Little is known about the memories of relatives after they have been confronted
      with the brain death of a loved one and the request for organ donation. We
      conducted this study, guided by Grounded Theory, to explore relatives'
      experiences, their interactions with health care providers and what influenced
      their memories. We interviewed 40 relatives (31 consenting to and 9 refusing
      organ donation) of 33 brain-dead individuals. Relatives described their
      experiences as a difficult process composed of several stages spanning from the
      initial encounter to the final decision about donation. Long-term memories of
      bereaved relatives were influenced by the characteristics of their decision
      making style (clear vs. ambivalent) and the perceived quality of the interaction
      with professionals on the intensive care unit. Organ-focused behavior of
      professionals and an ambivalent decision-making style of relatives appear to be
      risk factors for traumatic memories.

PMID- 17227570
TI  - Clinical Trial of the Pan-Caspase Inhibitor, IDN-6556, in Human Liver
      Preservation Injury.
AB  - Cold ischemia/warm reperfusion (CI/WR) injury remains a problem in liver
      transplantation. The aim of the current study was to assess the utility of the
      pan-caspase inhibitor IDN-6556 on CI/WR injury during human liver
      transplantation. This report is a post hoc analysis of a Phase II, multi-center,
      randomized, placebo-controlled, double-blinded, parallel group study. Subjects
      were assigned to four treatment groups: Group 1 (Organ storage/flush: Placebo
      Recipient: Placebo); Group 2 (Organ storage/flush: 15 microg/mL-Recipient:
      Placebo); Group 3 (Organ storage/flush: 5 microg/mL-Recipient: 0.5 mg/kg); and
      Group 4 (Organ storage/flush: 15 microg/mL-Recipient: 0.5 mg/kg). Liver cell
      apoptosis was assessed by serum concentrations of the apoptosis-associated
      CK18Asp396 ('M30') neo-epitope, TUNEL assay and caspase 3/7 immunohistochemistry.
      Liver injury was assessed by serum AST/ALT determinations. Serum markers of liver
      cell apoptosis were reduced in all groups receiving drug as compared to placebo.
      However, TUNEL, caspase 3/7 positive cells and serum AST/ALT levels were only
      consistently reduced in Group 2 (drug exposed to organ only). This reduction in
      serum transaminases was significant and observed across the study. In conclusion,
      IDN-6556 when administered in cold storage and flush solutions during liver
      transplantation offers local therapeutic protection against CI/WR-mediated
      apoptosis and injury. However, larger studies are required to confirm these
      observations.

PMID- 17227573
TI  - Utility versus utilization of DCD liver allografts.

PMID- 17227574
TI  - Transplantation of en bloc kidneys from very small pediatric donors.

PMID- 17227571
TI  - Renal allograft protection with angiotensin II type 1 receptor antagonists.
AB  - The renal benefits of agents inhibiting the renin-angiotensin-aldosterone system
      in renal transplant recipients, i.e. preventing the development of chronic graft
      nephropathy, are supposed but not finally proven. In a double-blind, placebo
      controlled, cross-over study, we evaluated the influence of losartan on surrogate
      markers of tubular injury, urine excretion of transforming growth factor beta-1
      (TGF-beta1) and amino-terminal propeptide of type III procollagen (PIIINP) in 16
      patients after transplantation. The patients received randomly either losartan
      (50-100 mg daily) or the beta-blocker carvedilol (12.5-25 mg) for 8 weeks,
      allowing a placebo washout between treatments. The target office through blood
      pressure (BP) was below 130/85 mmHg. The BP did not differ in the treatment
      periods. Losartan significantly decreased N-acetyl-beta-d-glucosaminidase and
      alfa-1 microglobulin excretion relative to placebo and carvedilol. Urine
      excretion of TGF-beta1 and PIIINP was significantly lower after losartan. In
      conclusion, losartan reduces urine excretion of proteins associated with tubular
      damage and graft fibrosis.

PMID- 17227575
TI  - An assessment of the RIFLE criteria for acute renal failure in critically ill HIV
      infected patients.

PMID- 17227576
TI  - Brain metastases as primary manifestation of a melanocytic malignant peripheral
      nerve sheath tumor in a 60-year-old man.
AB  - BACKGROUND: Malignant peripheral nerve sheath tumors are rare tumor entities that
      originate from peripheral nerve sheaths and have an unfavorable prognosis.
      Metastatic spread to the cerebral parenchyma is absolutely rare. This case report
      describes the clinical course in a 60-year-old man whose tumor came to medical
      attention because of a seizure. CASE PRESENTATION: Magnetic resonance imaging
      demonstrated two intracerebral lesions. The symptomatic lesion was removed
      microneurosurgically and histology demonstrated a metastasis from a malignant
      peripheral nerve sheath tumor. Postoperatively, whole-brain irradiation was
      performed. The primary tumor was identified in the area of the sciatic nerve on
      the right. Follow-up 14 months after resection showed that there was no
      progression of the intracerebral lesions but an increase in size and number of
      distant metastases. CONCLUSION: There are no generally accepted guidelines for
      the treatment of malignant peripheral nerve sheath tumors with cerebral
      metastases. This case report presents and discusses one possible therapeutic
      approach. Due to the poor overall prognosis, the least invasive therapy should be
      chosen.

PMID- 17227577
TI  - Effect of neural connectivity on autocovariance and cross covariance estimates.
AB  - BACKGROUND: Measurements of auto and cross covariance functions are frequently
      used to investigate neural systems. In interpreting this data, it is commonly
      assumed that the largest contribution to the recordings comes from sources near
      the electrode. However, the potential recorded at an electrode represents the
      superimposition of the potentials generated by large numbers of active neural
      structures. This creates situations under which the measured auto and cross
      covariance functions are dominated by the activity in structures far from the
      electrode and in which the distance dependence of the cross-covariance function
      differs significantly from that describing the activity in the actual neural
      structures. METHODS: Direct application of electrostatics to calculate the
      theoretical auto and cross covariance functions that would be recorded from
      electrodes immersed in a large volume filled with active neural structures with
      specific statistical properties. RESULTS: It is demonstrated that the potentials
      recorded from a monopolar electrode surrounded by dipole sources in a uniform
      medium are predominantly due to activity in neural structures far from the
      electrode when neuronal correlations drop more slowly than 1/r3 or when the size
      of the neural system is much smaller than a known correlation distance.
      Recordings from quadrupolar sources are strongly dependent on distant neurons
      when correlations drop more slowly than 1/r or the size of the system is much
      smaller than the correlation distance. Differences between bipolar and monopolar
      recordings are discussed. It is also demonstrated that the cross covariance of
      the recorded in two spatially separated electrodes declines as a power-law
      function of the distance between them even when the electrical activity from
      different neuronal structures is uncorrelated. CONCLUSION: When extracellular
      electrophysiologic recordings are made from systems containing large numbers of
      neural structures, it is important to interpret measured auto and cross
      covariance functions cautiously in light of the long range nature of the electric
      fields. Using recording electrodes that are bipolar or quadrupolar minimizes or
      eliminates these effects and hence these electrodes are preferred when electrical
      recordings are made for the purpose of auto and cross correlation analysis of
      local electrical activity.

PMID- 17227578
TI  - Cancer mortality trends in the Umbria region of Italy 1978-2004: a joinpoint
      regression analysis.
AB  - BACKGROUND: The aim of the present paper was to analyse cancer mortality in the
      Umbria region, from 1978 to 2004. Mortality trends depend on a number of factors
      including exposures, health system interventions, and possibly artefact (e.g.
      classification change, variations of data completeness). Descriptive data on
      mortality only allow for generation of hypotheses to explain observed trends.
      Some clues on the respective role of possible mortality determinants may be found
      comparing mortality with incidence and survival data. METHODS: Mortality data for
      the periods 1978-1993 and 1994-2004 were supplied by the National Institute of
      Statistics (ISTAT) and the Regional Causes of Death Registry (ReNCaM)
      respectively. Sex and site-specific mortality time trends were analysed by the
      "joinpoint regression" method. RESULTS: For all sites combined, in both sexes,
      the standardised rate was first increasing before the end of the eighties and
      decreasing thereafter. Gastric cancer mortality showed a different trend by
      gender; that is the rate constantly decreased over the period among females
      while, for males, it was first increasing up to 1985 and decreasing thereafter.
      Liver cancer trend showed a pattern similar to gastric cancer. Large bowel cancer
      showed a gender specific trend, that is it was increasing among males and stable
      among females. Also lung cancer mortality varied by gender: it started to decline
      after 1989 among males but was steadily increasing over the study period among
      women. A decreasing trend for female breast cancer mortality began in 1994.
      Prostate cancer mortality trend is the only one showing two significant
      joinpoints: mortality decreased up to 1990, then it increased up to 1998 and,
      finally, was decreasing. CONCLUSION: Overall cancer mortality was decreasing in
      both sexes in Umbria and this favourable trend will probably continue and further
      improve since population screening against breast, cervix, and large bowel
      cancers were recently introduced. Besides gastric cancer, tobacco-related cancers
      and prostate cancer mainly contributed to mortality reduction in males, whereas
      breast cancer mainly contributed to declining mortality in females.

PMID- 17227579
TI  - Directed cell migration in the presence of obstacles.
AB  - BACKGROUND: Chemotactic movement is a common feature of many cells and
      microscopic organisms. In vivo, chemotactic cells have to follow a chemotactic
      gradient and simultaneously avoid the numerous obstacles present in their
      migratory path towards the chemotactic source. It is not clear how cells detect
      and avoid obstacles, in particular whether they need a specialized biological
      mechanism to do so. RESULTS: We propose that cells can sense the presence of
      obstacles and avoid them because obstacles interfere with the chemical field. We
      build a model to test this hypothesis and find that this naturally enables
      efficient at-a-distance sensing to be achieved with no need for a specific and
      active obstacle-sensing mechanism. We find that (i) the efficiency of obstacle
      avoidance depends strongly on whether the chemotactic chemical reacts or remains
      unabsorbed at the obstacle surface. In particular, it is found that chemotactic
      cells generally avoid absorbing barriers much more easily than non-absorbing
      ones. (ii) The typically low noise in a cell's motion hinders the ability to
      avoid obstacles. We also derive an expression estimating the typical distance
      traveled by chemotactic cells in a 3D random distribution of obstacles before
      capture; this is a measure of the distance over which chemotaxis is viable as a
      means of directing cells from one point to another in vivo. CONCLUSION:
      Chemotactic cells, in many cases, can avoid obstacles by simply following the
      spatially perturbed chemical gradients around obstacles. It is thus unlikely that
      they have developed specialized mechanisms to cope with environments having low
      to moderate concentrations of obstacles.

PMID- 17227580
TI  - Phenotypes of myopathy-related actin mutants in differentiated C2C12 myotubes.
AB  - BACKGROUND: About 20 % of nemaline myopathies are thus far related to skeletal
      muscle alpha-actin. Seven actin mutants located in different parts of the actin
      molecule and linked to different forms of the disease were selected and expressed
      as EGFP-tagged constructs in differentiated C2C12 mytoubes. Results were compared
      with phenotypes in patient skeletal muscle fibres and with previous expression
      studies in fibroblasts and C2C12 myoblasts/myotubes. RESULTS: Whereas EGFP wt
      actin nicely incorporated into endogenous stress fibres and sarcomeric
      structures, the mutants showed a range of phenotypes, which generally changed
      upon differentiation. Many mutants appeared delocalized in myoblasts but
      integrated into endogenous actin structures after 4-6 days of differentiation,
      demonstrating a poor correlation between the appearance in myotubes and the
      severity of the disease. However, for some mutants, integration into stress
      fibres induced aberrant structures in differentiated cells, like thickening or
      fragmentation of stress fibres. Other mutants almost failed to integrate but
      formed huge aggregates in the cytoplasm of myotubes. Those did not co-stain with
      alpha-actinin, a main component of nemaline bodies found in patient muscle.
      Interestingly, nuclear aggregates as formed by two of the mutants in myoblasts
      were found less frequently or not at all in differentiated cells. CONCLUSION:
      Myotubes are a suitable system to study the capacity of a mutant to incorporate
      into actin structures or to form or induce pathological changes. Some of the
      phenotypes observed in undifferentiated myoblasts may only be in vitro effects.
      Other phenotypes, like aberrant stress fibres or rod formation may be more
      directly correlated with disease phenotypes. Some mutants did not induce any
      changes in the cellular actin system, indicating the importance of additional
      studies like functional assays to fully characterize the pathological impact of a
      mutant.

PMID- 17227581
TI  - Spot the match - wildlife photo-identification using information theory.
AB  - BACKGROUND: Effective approaches for the management and conservation of wildlife
      populations require a sound knowledge of population demographics, and this is
      often only possible through mark-recapture studies. We applied an automated spot
      recognition program (I3S) for matching natural markings of wildlife that is based
      on a novel information-theoretic approach to incorporate matching uncertainty.
      Using a photo-identification database of whale sharks (Rhincodon typus) as an
      example case, the information criterion (IC) algorithm we developed resulted in a
      parsimonious ranking of potential matches of individuals in an image library.
      Automated matches were compared to manual-matching results to test the
      performance of the software and algorithm. RESULTS: Validation of matched and non
      matched images provided a threshold IC weight (approximately 0.2) below which
      match certainty was not assured. Most images tested were assigned correctly;
      however, scores for the by-eye comparison were lower than expected, possibly due
      to the low sample size. The effect of increasing horizontal angle of sharks in
      images reduced matching likelihood considerably. There was a negative linear
      relationship between the number of matching spot pairs and matching score, but
      this relationship disappeared when using the IC algorithm. CONCLUSION: The
      software and use of easily applied information-theoretic scores of match
      parsimony provide a reliable and freely available method for individual
      identification of wildlife, with wide applications and the potential to improve
      mark-recapture studies without resorting to invasive marking techniques.

PMID- 17227583
TI  - Methods for peptide identification by spectral comparison.
AB  - BACKGROUND: Tandem mass spectrometry followed by database search is currently the
      predominant technology for peptide sequencing in shotgun proteomics experiments.
      Most methods compare experimentally observed spectra to the theoretical spectra
      predicted from the sequences in protein databases. There is a growing interest,
      however, in comparing unknown experimental spectra to a library of previously
      identified spectra. This approach has the advantage of taking into account
      instrument-dependent factors and peptide-specific differences in fragmentation
      probabilities. It is also computationally more efficient for high-throughput
      proteomics studies. RESULTS: This paper investigates computational issues related
      to this spectral comparison approach. Different methods have been empirically
      evaluated over several large sets of spectra. First, we illustrate that the peak
      intensities follow a Poisson distribution. This implies that applying a square
      root transform will optimally stabilize the peak intensity variance. Our results
      show that the square root did indeed outperform other transforms, resulting in
      improved accuracy of spectral matching. Second, different measures of spectral
      similarity were compared, and the results illustrated that the correlation
      coefficient was most robust. Finally, we examine how to assemble multiple spectra
      associated with the same peptide to generate a synthetic reference spectrum.
      Ensemble averaging is shown to provide the best combination of accuracy and
      efficiency. CONCLUSION: Our results demonstrate that when combined, these methods
      can boost the sensitivity and specificity of spectral comparison. Therefore they
      are capable of enhancing and complementing existing tools for consistent and
      accurate peptide identification.

PMID- 17227582
TI  - Calpain-5 gene variants are associated with diastolic blood pressure and
      cholesterol levels.
AB  - BACKGROUND: Genes implicated in common complex disorders such as obesity, type 2
      diabetes mellitus (T2DM) or cardiovascular diseases are not disease specific,
      since clinically related disorders also share genetic components. Cysteine
      protease Calpain 10 (CAPN10) has been associated with T2DM, hypertension,
      hypercholesterolemia, increased body mass index (BMI) and polycystic ovary
      syndrome (PCOS), a reproductive disorder of women in which isunlin resistance
      seems to play a pathogenic role. The calpain 5 gene (CAPN5) encodes a protein
      homologue of CAPN10. CAPN5 has been previously associated with PCOS by our group.
      In this new study, we have analysed the association of four CAPN5 gene
      variants(rs948976A>G, rs4945140G>A, rs2233546C>T and rs2233549G>A) with several
      cardiovascular risk factors related to metabolic syndrome in general population.
      METHODS: Anthropometric measurements, blood pressure, insulin, glucose and lipid
      profiles were determined in 606 individuals randomly chosen from a cross
      sectional population-based epidemiological survey in the province of Segovia in
      Central Spain (Castille), recruited to investigate the prevalence of
      anthropometric and physiological parameters related to obesity and other
      components of the metabolic syndrome. Genotypes at the four polymorphic loci in
      CAPN5 gene were detected by polymerase chain reaction (PCR). RESULTS: Genotype
      association analysis was significant for BMI (p < or = 0.041), diastolic blood
      pressure (p = 0.015) and HDL-cholesterol levels (p = 0.025). Different CAPN5
      haplotypes were also associated with diastolic blood pressure (DBP) (0.0005 < or
      = p < or = 0.006) and total cholesterol levels (0.001 < or = p < or = 0.029). In
      addition, the AACA haplotype, over-represented in obese individuals, is also more
      frequent in individuals with metabolic syndrome defined by ATPIII criteria (p =
      0.029). CONCLUSION: As its homologue CAPN10, CAPN5 seems to influence traits
      related to increased risk for cardiovascular diseases. Our results also may
      suggest CAPN5 as a candidate gene for metabolic syndrome.

PMID- 17227584
TI  - Historical trends in survival of hospitalized heart failure patients: 2000 versus
      1995.
AB  - BACKGROUND: Population-based secular trends in survival of patients with
      congestive heart failure (CHF) are central to public health research on the
      burden of the syndrome. METHODS: Patients 35-79 years old with a CHF discharge
      code in 1995 or 2000 were identified in 22 Minneapolis-St. Paul hospitals. A
      sample of the records was abstracted (50% of 1995 records; 38% of 2000 records).
      A total of 2,257 patients in 1995 and 1,825 patients in 2000 were determined to
      have had a CHF-related hospitalization. Each patient was followed for one year to
      ascertain vital status. RESULTS: The risk profile of the 2000 patient cohort was
      somewhat worse than that of the 1995 cohort in both sex groups, but the
      distributions of age and left ventricular ejection fraction were similar. Within
      one year of admission in 2000, 28% of male patients and 27% of female patients
      have died, compared to 36% and 27% of their counterparts in 1995, respectively.
      In various Cox regression models the average year effect (2000 vs. 1995) was
      around 0.75 for men and 0.95 to 1.00 for women. The use of angiotensin converting
      enzyme inhibitors and beta-blockers was associated with substantially lower
      hazard of death during the subsequent year. CONCLUSION: Survival of men who were
      hospitalized for CHF has improved during the second half of the 1990s. The trend
      in women was very weak, compatible with little to no change. Documented benefits
      of angiotensin converting-enzyme inhibitors and beta-blockers were evident in
      these observational data in both men and women.

PMID- 17227585
TI  - Breast cancer metastasis suppressor 1 (BRMS1) inhibits osteopontin transcription
      by abrogating NF-kappaB activation.
AB  - BACKGROUND: Osteopontin (OPN), a secreted phosphoglycoprotein, has been strongly
      associated with tumor progression and aggressive cancers. MDA-MB-435 cells
      secrete very high levels of OPN. However metastasis-suppressed MDA-MB-435 cells,
      which were transfected with breast cancer metastasis suppressor 1 (BRMS1),
      expressed significantly less OPN. BRMS1 is a member of mSin3-HDAC transcription
      co-repressor complex and has been shown to suppress the metastasis of breast
      cancer and melanoma cells in animal models. Hence we hypothesized that BRMS1
      regulates OPN expression. RESULTS: The search for a BRMS1-regulated site on the
      OPN promoter, using luciferase reporter assays of the promoter deletions,
      identified a novel NF-kappaB site (OPN/NF-kappaB). Electrophoretic mobility shift
      assays and chromatin immunoprecipitations (ChIP) confirmed this site to be an NF
      kappaB-binding site. We also show a role of HDAC3 in suppression of OPN via
      OPN/NF-kappaB. CONCLUSION: Our results show that BRMS1 regulates OPN
      transcription by abrogating NF-kappaB activation. Thus, we identify OPN, a tumor
      metastasis activator, as a crucial downstream target of BRMS1. Suppression of OPN
      may be one of the possible underlying mechanisms of BRMS1-dependent suppression
      of tumor metastasis.

PMID- 17227586
TI  - The association of the ankle-brachial index with incident coronary heart disease:
      the Atherosclerosis Risk In Communities (ARIC) study, 1987-2001.
AB  - BACKGROUND: Peripheral arterial disease (PAD), defined by a low ankle-brachial
      index (ABI), is associated with an increased risk of cardiovascular events, but
      the risk of coronary heart disease (CHD) over the range of the ABI is not well
      characterized, nor described for African Americans. METHODS: The ABI was measured
      in 12186 white and African American men and women in the Atherosclerosis Risk in
      Communities Study in 1987-89. Fatal and non-fatal CHD events were ascertained
      through annual telephone contacts, surveys of hospital discharge lists and death
      certificate data, and clinical examinations, including electrocardiograms, every
      3 years. Participants were followed for a median of 13.1 years. Age- and field
      center-adjusted hazard ratios (HRs) were estimated using Cox regression models.
      RESULTS: Over a median 13.1 years follow-up, 964 fatal or non-fatal CHD events
      accrued. In whites, the age- and field-center-adjusted CHD hazard ratio (HR, 95%
      CI) for PAD (ABI<0.90) was 2.81 (1.77-4.45) for men and 2.05 (1.20-3.53) for
      women. In African Americans, the HR for men was 4.86 (2.76-8.47) and for women
      was 2.34 (1.26-4.35). The CHD risk increased exponentially with decreasing ABI as
      a continuous function, and continued to decline at ABI values > 1.0, in all race
      gender subgroups. The association between the ABI and CHD relative risk was
      similar for men and women in both race groups. A 0.10 lower ABI increased the CHD
      hazard by 25% (95% CI 17-34%) in white men, by 20% (8-33%) in white women, by 34%
      (19-50%) in African American men, and by 32% (17-50%) in African American women.
      CONCLUSION: African American members of the ARIC cohort had higher prevalences of
      PAD and greater risk of CHD associated with ABI-defined PAD than did white
      participants. Unlike in other cohorts, in ARIC the CHD risk failed to increase at
      high (>1.3) ABI values. We conclude that at this time high ABI values should not
      be routinely considered a marker for increased CVD risk in the general
      population. Further research is needed on the value of the ABI at specific
      cutpoints for risk stratification in the context of traditional risk factors.

PMID- 17227587
TI  - Skeletal muscle oxygen saturation does not estimate mixed venous oxygen
      saturation in patients with severe left heart failure and additional severe
      sepsis or septic shock.
AB  - INTRODUCTION: Low cardiac output states such as left heart failure are
      characterized by preserved oxygen extraction ratio, which is in contrast to
      severe sepsis. Near infrared spectroscopy (NIRS) allows noninvasive estimation of
      skeletal muscle tissue oxygenation (StO2). The aim of the study was to determine
      the relationship between StO2 and mixed venous oxygen saturation (SvO2) in
      patients with severe left heart failure with or without additional severe sepsis
      or septic shock. METHODS: Sixty-five patients with severe left heart failure due
      to primary heart disease were divided into two groups: groups A (n = 24) and B (n
      = 41) included patients without and with additional severe sepsis/septic shock,
      respectively. Thenar muscle StO2 was measured using NIRS in the patients and in
      15 healthy volunteers. RESULTS: StO2 was lower in group A than in group B and in
      healthy volunteers (58 +/- 13%, 90 +/- 7% and 84 +/- 4%, respectively; P <
      0.001). StO2 was higher in group B than in healthy volunteers (P = 0.02). In
      group A StO2 correlated with SvO2 (r = 0.689, P = 0.002), although StO2
      overestimated SvO2 (bias -2.3%, precision 4.6%). In group A changes in StO2
      correlated with changes in SvO2 (r = 0.836, P < 0.001; DeltaSvO2 = 0.84 x
      DeltaStO2 - 0.67). In group B important differences between these variables were
      observed. Plasma lactate concentrations correlated negatively with StO2 values
      only in group A (r = -0.522, P = 0.009; lactate = -0.104 x StO2 + 10.25).
      CONCLUSION: Skeletal muscle StO2 does not estimate SvO2 in patients with severe
      left heart failure and additional severe sepsis or septic shock. However, in
      patients with severe left heart failure without additional severe sepsis or
      septic shock, StO2 values could be used to provide rapid, noninvasive estimation
      of SvO2; furthermore, the trend in StO2 may be considered a surrogate for the
      trend in SvO2.

PMID- 17227588
TI  - Lentiviral-mediated gene correction of mucopolysaccharidosis type IIIA.
AB  - BACKGROUND: Mucopolysaccharidosis type IIIA (MPS IIIA) is the most common of the
      mucopolysaccharidoses. The disease is caused by a deficiency of the lysosomal
      enzyme sulphamidase and results in the storage of the glycosaminoglycan (GAG),
      heparan sulphate. MPS IIIA is characterised by widespread storage and urinary
      excretion of heparan sulphate, and a progressive and eventually profound
      neurological course. Gene therapy is one of the few avenues of treatment that
      hold promise of a sustainable treatment for this disorder. METHODS: The murine
      sulphamidase gene cDNA was cloned into a lentiviral vector and high-titre virus
      produced. Human MPS IIIA fibroblast cultures were transduced with the
      sulphamidase vector and analysed using molecular, enzymatic and metabolic assays.
      High-titre virus was intravenously injected into six 5-week old MPS IIIA mice.
      Three of these mice were pre-treated with hyperosmotic mannitol. The weight of
      animals was monitored and GAG content in urine samples was analysed by
      polyacrylamide gel electrophoresis. RESULTS: Transduction of cultured MPS IIIA
      fibroblasts with the sulphamidase gene corrected both the enzymatic and metabolic
      defects. Sulphamidase secreted by gene-corrected cells was able to cross correct
      untransduced MPS IIIA cells. Urinary GAG was found to be greatly reduced in
      samples from mice receiving the vector compared to untreated MPS IIIA controls.
      In addition, the weight of treated mice became progressively normalised over the
      6-months post-treatment. CONCLUSION: Lentiviral vectors appear promising vehicles
      for the development of gene therapy for MPS IIIA.

PMID- 17227590
TI  - Clear cell carcinoid tumor of the distal common bile duct.
AB  - BACKGROUND: Carcinoid tumors rarely arise in the extrahepatic bile duct and can
      be difficult to distinguish from carcinoma. There are no reports of clear cell
      carcinoid (CCC) tumors in the distal bile duct (DBD) to the best of our
      knowledge. Herein, we report a CCC tumor in the DBD and review the literature
      concerning extrahepatic bile duct carcinoid tumors. CASE PRESENTATION: A 73-old
      man presented with fever and occult obstructive jaundice. Ultrasonography,
      computed tomography (CT) and magnetic resonance cholangiopancreaticography (MRCP)
      demonstrated a nodular tumor projection in the DBD without regional lymph node
      swelling. Under suspicion of carcinoma, we resected the head of the pancreas
      along with 2nd portion duodenectomy and a lymph node dissection. The surgical
      specimen showed a golden yellow polypoid tumor in the DBD (0.8 x 0.6 x 0.5 cm in
      size). The lesion was composed of clear polygonal cells arranged in nests and a
      trabecular pattern. The tumor invaded through the wall into the fibromuscular
      layer. Immunohistochemical stains showed that neoplastic cells were positive for
      neuron-specific enolase (NSE), chromogranin A, synaptophysin, and pancreatic
      polypeptide and negative for inhibin, keratin, CD56, serotonin, gastrin and
      somatostatin. The postoperative course was uneventful and he is living well
      without relapse 12 months after surgery. CONCLUSION: Given the preoperative
      difficulty in differentiating carcinoid from carcinoma, the
      pancreaticoduodenectomy is an appropriate treatment choice for carcinoid tumors
      located within the intra-pancreatic bile duct.

PMID- 17227589
TI  - An increase in dietary n-3 fatty acids decreases a marker of bone resorption in
      humans.
AB  - Human, animal, and in vitro research indicates a beneficial effect of appropriate
      amounts of omega-3 (n-3) polyunsaturated fatty acids (PUFA) on bone health. This
      is the first controlled feeding study in humans to evaluate the effect of dietary
      plant-derived n-3 PUFA on bone turnover, assessed by serum concentrations of N
      telopeptides (NTx) and bone-specific alkaline phosphatase (BSAP). Subjects (n =
      23) consumed each diet for 6 weeks in a randomized, 3-period crossover design: 1)
      Average American Diet (AAD; [34% total fat, 13% saturated fatty acids (SFA), 13%
      monounsaturated fatty acids (MUFA), 9% PUFA (7.7% LA, 0.8% ALA)]), 2) Linoleic
      Acid Diet (LA; [37% total fat, 9% SFA, 12% MUFA, 16% PUFA (12.6% LA, 3.6% ALA)]),
      and 3) alpha-Linolenic Acid Diet (ALA; [38% total fat, 8% SFA, 12% MUFA, 17% PUFA
      (10.5% LA, 6.5% ALA)]). Walnuts and flaxseed oil were the predominant sources of
      ALA. NTx levels were significantly lower following the ALA diet (13.20 +/- 1.21
      nM BCE), relative to the AAD (15.59 +/- 1.21 nM BCE) (p < 0.05). Mean NTx level
      following the LA diet was 13.80 +/- 1.21 nM BCE. There was no change in levels of
      BSAP across the three diets. Concentrations of NTx were positively correlated
      with the pro-inflammatory cytokine TNFalpha for all three diets. The results
      indicate that plant sources of dietary n-3 PUFA may have a protective effect on
      bone metabolism via a decrease in bone resorption in the presence of consistent
      levels of bone formation.

PMID- 17227592
TI  - Endometriosis: disease pathophysiology and the role of prostaglandins.
AB  - Endometriosis is considered to be a polygenic disease with a complex,
      multifactorial aetiology that affects about 10% of women in the reproductive age.
      Women with endometriosis have symptoms that include chronic pelvic pain,
      dysmenorrhoea and dyspareunia, significantly reducing their quality of life.
      Endometriosis is also the primary cause of infertility in women, with the
      prevalence rate ranging from 20% to 50%. The high prevalence and severe outcomes
      of this disease have made it a major public health concern in modern society.
      Currently, the mechanism(s) responsible for the initiation and promotion of this
      disease remains obscure. In this review, we focus on the expression, regulation
      and action of prostaglandins in the cellular and molecular mechanisms that
      contribute to the development and/or maintenance of endometriosis.

PMID- 17227591
TI  - Intra-abdominal pressure in severe acute pancreatitis.
AB  - BACKGROUND: Hospital mortality in patients with severe acute pancreatitis (SAP)
      remains high. Some of these patients develop increased intra-abdominal pressure
      (IAP) which may contribute to organ dysfunction. The aims of this study were to
      evaluate the frequency of increased IAP in patients with SAP and to assess the
      development of organ dysfunction and factors associated with high IAP. METHODS:
      During 2001-2003 a total of 59 patients with severe acute pancreatitis were
      treated in the intensive care unit (ICU) of Helsinki University Hospital. IAP was
      measured by the intravesical route in 37 patients with SAP. Data from these
      patients were retrospectively reviewed. RESULTS: Maximal IAP, APACHE II score,
      maximal SOFA score, maximal creatinine, age and maximal lactate were
      significantly higher in nonsurvivors. There was a significant correlation of the
      maximal IAP with the maximal SOFA, APACHE II, maximal creatinine, maximal
      lactate, base deficit and ICU length of stay. Patients were divided into
      quartiles according to the maximal IAP. Maximal IAP was 7-14, 15-18, 19-24 and 25
      33 mmHg and the hospital mortality rate 10%, 12.5%, 22.2% and 50% in groups 1-4,
      respectively. A statistically significant difference was seen in the maximal
      SOFA, ICU length of stay, maximal creatinine and lactate values. The mean ICU
      free days in groups 1-4 were 45.7, 38.8, 32.0 and 27.5 days, respectively. The
      difference between groups 1 and 4 was statistically significant. CONCLUSION: In
      patients with SAP, increased IAP is associated with development of early organ
      failure reflected in increased mortality and fewer ICU-free days. Frequent
      measurement of IAP during intensive care is important in optimizing abdominal
      perfusion pressure and recognizing patients potentially benefitting from
      decompressive laparotomy.

PMID- 17227595
TI  - Evaluation of milk components during whole lactation in healthy quarters.
AB  - Several milk components related to immune defences (lysozyme, lactoferrin and
      gamma-globulins, gamma-G) and to inflammation (somatic cell counts, SCC; N-acetyl
      beta-glucosaminidase, NAGase; albumin) were considered. Forty-one quarters and
      685 samples of 24 cows were included in the study; among them 534 samples were
      defined as negative (78.0%), 93 as diseased (13.5%) and 58 (8.5%) as subclinical.
      The pattern of each milk component in quarters always negative during the follow
      up period was evaluated by a mixed model. Statistical analysis showed that days
      in milk (DIM), age (primiparous, pluriparous), herd and the interaction between
      herd and days in milk significantly influenced all the markers, with very few
      exceptions. A subset of samples including the negative quarters before the first
      outcome of an infection or a subclinical mastitis and the samples from quarters
      always negative was also selected. The analysis showed that herd, DIM and health
      status had a significant influence on most markers. Overall, primiparous cows
      were confirmed to have higher levels of most of the markers than pluriparous
      cows. The presence of a herd effect on non specific immune defences in fully
      negative quarters implies that when the mechanisms behind their release are fully
      elucidated, it might be possible to modulate them. Udder tissues were confirmed
      as an important source of some immune components, as supported by the
      inconsistency between SCC mean values and NAGase, lysozyme and lactoferrin
      values. Overall, quarters with high levels of NAGase, lysozyme and gamma-G,
      exposed to bacteria, did not develop subclinical mastitis. Hence, invading
      pathogens could induce the development of subclinical IMI when these components
      and gammaG are in low concentration.

PMID- 17227594
TI  - Aetiology of intramammary infection and its effect on milk composition in goat
      flocks.
AB  - Although there has been little study of the origin of intramammary infection
      (IMI) in goats, a common view is that most bacterial infection in goats occurs
      during milking. In the present study, the dynamics of occurrence of udder
      infection during and between lactations in three Anglo-Nubian goat farms in
      Israel was monitored. Coagulase-negative staphylococci were the predominant
      bacteria in the IMIs. We found that about 15% of the yearling does were already
      infected with bacteria when they joined the flock, whereas about 8% of the goats
      that dried-off returned with new IMIs. Moreover, virtually none of the goats
      acquired infection during lactation. Thus, our study showed that the aetiology of
      IMI in goats is very similar to that in dairy cows. A preventive treatment during
      the dry period should, therefore, be considered as an effective means of reducing
      the current rate of bacterial infections in goats.

PMID- 17227593
TI  - Effects of feeding two levels of propionibacteria to dairy cows on plasma
      hormones and metabolites.
AB  - To determine the effect of feeding propionibacteria on metabolic indicators
      during lactation, multiparous and primiparous Holstein cows were fed one of three
      dietary treatments in a 2 x 3 factorial design from 2 weeks prepartum to 30 weeks
      post partum: (1) Control (primiparous n=5, multiparous n=8) fed a total mixed
      ration (TMR); (2) high-dose group (primiparous n=6, multiparous n=5) fed TMR plus
      6 x 10 (11) cfu/head daily (high-dose P169) of propionibacterium strain P169; or
      (3) low-dose group (primiparous n=8, multiparous n=6) fed TMR plus 6 x 10(10)
      cfu/head daily (low-dose P169) of P169. Blood samples were collected weekly and
      analysed for plasma concentrations of glucose, insulin, insulin-like growth
      factor-I (IGF-I), leptin, nonesterified fatty acids (NEFA) and cholesterol.
      Between weeks 25 and 30, all groups received bovine somatotropin (bST) every 2
      weeks. Low-dose P169 multiparous cows had lower (P<0.05) plasma insulin and
      glucose concentrations than high-dose P169 multiparous cows, whereas high-dose
      P169 primiparous cows had lower glucose but greater insulin concentartions than
      low-dose P169 primiparous cows (P<0.05). Plasma insulinratioglucose molar ratios
      were 13-18% lower (P<0.05) in low-dose P169 cows than in control or high-dose
      P169 cows. Plasma IGF-I, NEFA and leptin levels did not differ among diet groups
      between weeks 1 and 25. Low-dose P169 multiparous cows had 25% greater plasma
      cholesterol levels than high-dose P169 and control multiparous cows, but
      cholesterol levels in primiparous cows did not differ. During bST treatment, high
      dose P169 multiparous cows and low-dose P169 primiparous cows had lower IGF-I
      levels than their respective controls and, regardless of parity, high-dose P169
      cows had greater NEFA than control cows. Although supplemental feeding of P169
      altered plasma hormones and metabolites, the particular effects were dependent on
      dose of P169 and parity of cows.

PMID- 17227596
TI  - Haptoglobin and serum amyloid A in relation to the somatic cell count in quarter,
      cow composite and bulk tank milk samples.
AB  - Milk somatic cell count (SCC) is the gold standard in diagnosis of subclinical
      mastitis, and is also an important parameter in quality programmes of dairy
      cooperatives. As routine SCC analysis is usually restricted to central
      laboratories, much effort has been invested in the search for alternative
      biomarkers of mastitis and milk quality, including the presence in the milk of
      the acute phase proteins (APP), haptoglobin (Hp) and serum amyloid A (SAA). The
      aim of this study was to investigate relationships between Hp, SAA and SCC in
      quarter, cow composite, and bulk tank milk samples. Cows (n=165), without any
      clinical signs of disease or abnormalities in the milk or udder, from three
      different dairy farms, were used. Cow composite milk samples from all cows
      delivering milk at the sampling occasion were taken once in each herd. In one of
      the farms, representative quarter milk samples (n=103) from 26 cows were also
      collected. In addition, bulk tank milk samples from 96 dairy farms were included
      in the study. Samples were analysed for Hp, SAA and SCC, and relationships
      between the parameters were evaluated at quarter, cow and tank milk levels using
      Chi-square analysis. Milk samples were categorized according to their SCC, and
      the presence, or no presence, of SAA and Hp, based on the detection limits of the
      screening methods (0.3 mg/l and 1.0 mg/l for SAA and Hp, respectively). Hp and
      SAA were found in milk at quarter, cow composite and bulk tank levels. A large
      proportion (53%) of the animals had detectable milk concentrations of APP, and
      SAA was detected more frequently, and at higher concentrations than Hp,
      regardless of sample type. SAA was detected in as many as 82% of the bulk tank
      milk samples. Significant relationships were found between Hp, SAA and SCC at
      quarter and cow composite milk levels, but only between SAA and SCC at bulk tank
      milk level. Detectable levels of APP were more common at high SCC.

PMID- 17227597
TI  - Cell function in the bovine mammary gland: a preliminary study on interdependence
      of healthy and infected udder quarters.
AB  - Udder defence mechanisms are not completely explained by current mastitis
      research. The anatomical construction of the udder implies that infection of one
      udder quarter does not influence the immune status of neighbouring quarters. To
      test this hypothesis, we compared the immune reactions of individual udder
      quarters in response to microbial attacks. In the course of immune reactions,
      polymorphonuclear leucocytes (PMN) release oxygen radicals, which can be
      determined by chemiluminescence (CL). Milk from 140 udder quarters of 36 cows was
      analysed for somatic cell count (SCC), differential cell count, viability and CL
      activity. Quarters with an SCC < 100,000 cells/ml and free of pathogens were
      defined as uninfected, all other quarters were categorized as infected. Three
      groups of cows were classified cytologically: group A (healthy, 11 animals, SCC
      limit < 100,000 cells/ml); group B (moderate mastitis, 8 cows, SCC > or = 100,000
      and < 400,000 cells/ml in at least one quarter); and group C (severe mastitis, 17
      cows, SCC > or = 400,000 cells/ml in at least one quarter). Infected and
      uninfected quarters in groups B and C were analysed separately. Viability of PMN
      leucocytes was significantly (P=0.0012) lower in group A (72.6%) than in healthy
      quarters of group C (84.0%). Lowering the SCC limit of healthy quarters to
      <50,000 cells/ml (group A: all quarters within the udder) revealed striking
      differences between samples of groups B and C: in addition to varying
      differential cell counts and viabilities, CL activity of group B<50 (2929 CL
      units/million PMN) was markedly lower than that of the other groups (5616 in
      group A<50 and 6445 CL units/million PMN in group C<50). These results allow the
      conclusion that the infection of one udder quarter influences the cell activity
      of neighbouring quarters. When the SCC threshold for healthy quarters was reduced
      to 50,000 cells/ml, greater differences in cell activities were detected between
      healthy udders and healthy quarters of infected udders.

PMID- 17227599
TI  - Effect of subclinical intramammary infection on somatic cell counts and chemical
      composition of goats' milk.
AB  - We investigated effects of subclinical intramammary infection (IMI) on milk
      somatic cell count (SCC) and milk composition in udder halves of dairy goats. A
      total of 35 mixed-age Alpine does (70 udder halves; approximately 55 kg body
      weight) were rotationally grazed on a mixture of vegetative forages
      (wheat/berseem clover, sudan grass and cowpeas). Milk samples for bacterial
      analysis and SCC were collected monthly from both halves from April to September,
      2001. Across stages of lactation, 19-31% of udder halves became infected. The
      prevalence of IMI exhibited quadratic patterns through multi-peaked responses
      within each stage of lactation. Higher rates of IMI were observed during the
      early stage of lactation (19% in May) and in the late stage of lactation (31% in
      September). Coagulase negative Staphylococcus (CNS, 43.7%), Staph. aureus
      (35.4%), and Pseudomonas aeruginosa (12.4%) were the most prevalent pathogens.
      Within single-strain IMI, log SCC (6.24) was lower (P<0.01) for CNS than those
      derived from IMI by Staph. aureus (6.49), Ps. aeruginosa (6.53) or Serratia spp.
      (6.90). Infected udder halves had a higher average SCC (4761 v. 2259 x 10(3)
      cells/ml; P<0.01) than uninfected halves, but uninfected halves often had similar
      levels of SCC to infected halves. Daily average milk production was not
      significantly different between infected and non-infected goats and the
      relationship between IMI and SCC was not always correlated. Effective mastitis
      screening requires bacteriological culture since SCC was not highly correlated.

PMID- 17227598
TI  - Intramammary infections in heifers during early lactation following intramammary
      infusion of pirlimycin hydrochloride or penicillin-novobiocin at the first
      milking after parturition.
AB  - A study was conducted to determine whether intramammary antibiotic treatment of
      heifer mammary glands following the first milking after calving was effective for
      reducing the percentage of mammary quarters infected during early lactation.
      Jersey and Holstein heifers from two research herds were assigned to one of three
      treatment groups: (1) no intramammary infusion following the first milking after
      parturition, (2) intramammary infusion of all quarters with pirlimycin
      hydrochloride following the first milking after parturition and (3) intramammary
      infusion of all quarters with novobiocin sodium plus penicillin G procaine
      following the first milking after parturition. Almost 93% of Jersey heifers
      (40/43) and 73.1% of quarters (125/171) were infected at the first milking.
      Almost 77% of quarters (33/43) were cured following treatment with pirlimycin,
      61.8% (21/34) were cured following treatment with penicillin-novobiocin and 39.6%
      (19/48) of infections were eliminated spontaneously in the untreated control
      group. Significantly fewer infections were observed in pirlimycin or penicillin
      novobiocin treated mammary glands of Jersey heifers during early lactation than
      in untreated control mammary glands. Almost 89% of Holstein heifers (32/36) and
      52.8% of quarters (76/144) were infected at the first milking. About 57% (12/21)
      of quarters were cured following treatment with pirlimycin, 41.4% (12/29) were
      cured following treatment with penicillin-novobiocin and 23.1% (6/26) of
      infections were eliminated spontaneously in the untreated negative control group.
      Significantly fewer infections were observed in pirlimycin treated mammary glands
      of Holstein heifers during early lactation than in untreated control mammary
      glands. However, no significant differences were observed following penicillin
      novobiocin treatment of Holstein heifers after the first milking of lactation
      compared with untreated control quarters. Coagulase-negative staphylococci,
      Streptococcus uberis and Streptococcus dysgalactiae subsp dysgalactiae were
      isolated most frequently in heifers from both herds.

PMID- 17227600
TI  - The emerging role of telemedicine in diagnosing and treating sleep disorders.
AB  - Over one-third of adults are at risk of developing sleep disorders. Telemedicine
      is emerging as an effective tool in sleep medicine by allowing people to undergo
      sleep studies without overnight hospital stays (e.g. monitoring at home).
      Telemedicine has the potential to overcome several obstacles in the diagnosis and
      treatment of sleep disorders by offering increased access to sleep specialists,
      enhancing health-care support for patients in their homes and providing cost
      effective professional education. The initial costs for telemedicine equipment
      and training are not insignificant; however, the benefits may outweigh the
      expense over time. However, recapturing the initial costs cannot be assumed.

PMID- 17227601
TI  - Experience with asynchronous medical teleconsultation in the Alliance of the
      Italian hospitals worldwide.
AB  - A store-and-forward teleconsultation system was established for 36 Italian
      hospitals located in 22 different countries. Referrals were made to a network of
      33 health centres in Italy via a management centre (MC). The MC was equipped with
      a server to manage the service. The participating hospitals used client
      workstations with special software. The referring centres generated
      teleconsultation requests, which were sent to the MC and allocated manually by
      the latter to the most appropriate specialist on the basis of information
      provided in the message. From 1 June 2005 to 15 March 2006, 187 enquiries out of
      221 were answered. The median response time was two days. A service satisfaction
      survey was conducted among the users and about 90% of the responses were
      positive. The teleconsultation system represents a mechanism for providing
      equitable access to health care for all the referring doctors.

PMID- 17227602
TI  - Four years experience with teleneuropathology.
AB  - Between 2002 and 2005, we made 343 intraoperative frozen section diagnoses with a
      telepathology system, which connected a neurosurgical department to our
      department of pathology. An expert neuropathologist performed at least one brief
      gross examination, and this was followed by a smear preparation and a frozen
      section slide for each case. Frozen section diagnosis lasted on average 26.1 min,
      calculated from the beginning of gross examination until the surgeon was given
      the diagnosis. The majority of cases (283 or 83%) were diagnosed in 15-40 min.
      The mean time needed for macroscopic examination was 3.0 min, time for staining
      4.2 min, smear diagnosis took 5.4 min and time for histological diagnosis 10.7
      min. Telemicroscopy of a smear slide took 11 times longer compared with light
      microscopy, and telemicroscopy of a frozen section slide took 16 times longer
      than with light microscopy. In 6% of cases, the telepathology software posed
      technical problems, which delayed the time of diagnosis, but not by more than 4
      min. We were able to render a diagnosis in all cases (system reliability 100%).
      After eliminating sampling errors (i.e. cases with no diagnostic material in the
      frozen section slides and/or in smear preparations), the diagnostic accuracy for
      telepathology was 97.9%.

PMID- 17227603
TI  - A qualitative comparative analysis of the conditions affecting early maternal
      transfer patterns.
AB  - In Arkansas, almost all of the high-risk-pregnancy resources are concentrated in
      a single place, at the University of Arkansas for Medical Sciences (UAMS). During
      the 6-month period before a telemedicine programme started, there were five
      operational telemedicine sites in the state, and during the subsequent 12-month
      period, there were 13 telemedicine sites in operation. Data were gathered on
      birth-related transfers during the two periods. Qualitative comparative analysis
      (QCA) was used to assess the effect of different combinations of telemedical and
      hospital-level resources on the timing of maternal transfers. Early (pre-33-week
      gestational age) maternal transfers occurred in period 1 (before the telemedicine
      programme started), only from areas with level-2 hospital resources and no
      telemedicine access; early transfers also occurred in period 2 from areas with
      level-2 hospital resources and either telemedicine access or no telemedicine
      access. We conclude that combinations of resources affect physician decisions
      regarding transfer and that QCA is a useful tool for examining the growth and
      development of telemedicine systems.

PMID- 17227604
TI  - A therapeutic alliance can exist without face-to-face contact.
AB  - We examined the therapeutic alliance in 64 parents who completed treatment with a
      non-professional telephone coach in a paediatric psychosocial and behavioural
      intervention study called Family Help. The mean total Working Alliance Inventory
      score was 242.7 (95% confidence interval [CI]: 240.2, 245.2). Overall, the total
      scores were very high regardless of coach/parental age or gender, socioeconomic
      class/educational level of the parent, severity or type of the child's mental
      health disorder or modality of treatment delivery. The results were compared with
      normative data reported from other studies, which suggested that the distance
      therapeutic alliance scores were at least similar to face-to-face therapeutic
      alliance scores. The present study provides evidence that a strong, positive
      therapeutic alliance can exist in the absence of face-to-face contact using non
      professional telephone coaches.

PMID- 17227605
TI  - An assessment of the video image quality required in a remote vision guidance
      system for visually impaired pedestrians.
AB  - A study was carried out to determine the most acceptable quality of video images
      for use in remote guidance of visually impaired pedestrians. A video image clip
      of 20 s duration was captured using a digital camera, while walking a sample
      route. The video image clip was encoded at bit rates of 30 and 48 kbit/s, and
      frame rates of 10, 7.5, 5 and 2.7 fps. Two standard resolutions were used:
      Quarter Common Intermediate Format (QCIF) (176 x 144 pixels) and Common
      Intermediate Format (CIF) (352 x 288 pixels). Twelve participants gave their
      judgment on the picture update rate (smoothness of movement), the bit rate and
      the static resolution. The mean scores for total quality (five-point scale)
      ranged from 3.3 to 4.8, but there was no significant difference between them. The
      mean scores for smoothness (five-point scale) ranged from 3.0 to 4.7, but there
      was no significant difference between them. The mean score for the resolution of
      the QCIF video clips was 2.9 (SD = 0.9) and for the CIF recordings were 4.1 (SD =
      0.7), but there was no significant difference between them. The majority of the
      participants were most comfortable with video which was transmitted at 48 kbit/s
      and 7.5 fps. Therefore, this quality can be considered satisfactory for remote
      guidance.

PMID- 17227606
TI  - Perspectives from the Veterans Health Administration about opportunities and
      barriers in telemedicine.
AB  - We used qualitative interviews to examine the perceptions of direct providers of
      telemedicine services, primary care providers (PCPs) and hospital administrators
      about opportunities and barriers to the implementation of telemedicine services
      in a network of Veterans Health Administration hospitals. A total of 37
      interviews were conducted (response rate of 28%) with 17 direct telemedicine
      providers, nine PCPs and 11 administrators. The overall inter-coder reliability
      across all themes was high (Scott's pi = 0.94). Direct telemedicine providers
      generally agreed that telemedicine improved rapport with patients, and
      respondents in all three groups generally agreed that telemedicine improves
      access, productivity, and the quality and coordination of care. Respondents
      mentioned several benefits to home telemedicine, including the ability to better
      manage chronic diseases, provide frequent clinician contact, facilitate quick
      responses to patient needs and provide care in patient's homes. Most respondents
      anticipated future growth in telemedicine services. Barriers to telemedicine
      implementation included technical challenges, the need for more education and
      training for patients and staff, preferences for in-person care, the need for
      programme improvement and the need for additional staff time to provide
      telemedicine services.

PMID- 17227607
TI  - Randomized controlled trial of the effectiveness of an intervention to implement
      evidence-based patient decision support in a nursing call centre.
AB  - We evaluated the effect of an intervention on call centre nurses' knowledge of
      decision support and skills in coaching callers facing value-sensitive health
      decisions. Forty-one registered nurses at a health call centre were randomly
      assigned to an intervention or control group. The intervention was a coaching
      protocol, online tutorial, skills building workshop and performance feedback. The
      main outcome measures were: knowledge test; blinded quality assessment of
      coaching skills during simulated calls and call duration. Compared with controls,
      nurses in the intervention group had better knowledge (74 versus 60%, P = 0.007)
      and decision coaching skills (81 versus 44%, P < 0.001), particularly in
      assessing decisional needs (information, values clarity, support, stage and
      timing of decision) and addressing support issues. Call duration did not differ
      (18.5 versus 16.7 min, P = 0.73). The coaching protocol was rated as compatible
      with nurses' views on decision-making and more advantageous compared with their
      usual practices. The intervention improved the quality of nurses' decision
      coaching without affecting call duration.

PMID- 17227608
TI  - Accuracy of paediatric echocardiographic transmission via telemedicine.
AB  - We evaluated the accuracy of realtime echocardiography studies conducted via
      telemedicine (at 384 kbit/s) and prerecorded video studies, by comparing the
      results with subsequent in-person echocardiography examination performed at
      follow-up. Between January 2002 and December 2004, there were 769 paediatric echo
      studies of patients aged one day to 19 years by telemedicine. There were three
      cases (0.4%) in which the study could not be successfully transmitted in realtime
      due to ISDN line or equipment failure. These were recorded, then transmitted and
      reviewed within 24 h. A normal heart was demonstrated in 272 studies (35%). A non
      urgent congenital heart defect (CHD) was detected in 311 studies (41%). A
      critical cardiac abnormality was identified in 25 studies (3% of the total).
      Sixty-seven studies were repeated in person at the tertiary centre. All but one
      of the follow-up echocardiograms confirmed our initial telemedicine diagnosis
      (99% sensitivity). There were 655 videorecorded studies delivered to the tertiary
      centre between February 2002 and November 2003. Thirty-two patients had a
      repeated echocardiogram performed there. There were either discrepancies or lack
      of diagnostic clarity in 12 studies (38%) compared with on-site echo evaluations.
      This suggests that echocardiography evaluation using videorecordings may be less
      accurate than via realtime telemedicine.

PMID- 17227609
TI  - Preliminary evaluation of the use of a CDMA-based emergency telemedicine system.
AB  - We have conducted a preliminary evaluation of the use of a code division multiple
      access (CDMA)-based emergency telemedicine system to be used by emergency
      rescuers providing first-aid treatment for patients. The prototype system
      included five instrumentation modules for measuring non-invasive arterial blood
      pressure (NIBP), arterial oxygen saturation (SpO(2)), six-channel
      electrocardiogram (ECG), blood glucose concentration and body temperature. The
      patient data were transferred to a doctor's PC through CDMA and TCP/IP networks
      using an embedded personal digital assistant (PDA) phone. Performance tests in
      the laboratory showed that the system provided reliable values with error ranges
      within +/-1% for heart rate, +/-5 mmHg for NIBP, +/-2% for SpO(2) and +/-1% for
      glucose. The feasibility of the prototype system was then evaluated with 15 real
      emergency patients on Jeju Island over a two-month period. Measured data were
      transmitted from a moving ambulance to the emergency medical centre without
      significant CDMA connection loss or transmission errors. The average transfer
      time was 8 min. Four emergency doctors and 11 rescuers completed a questionnaire.
      There were favourable reviews from the users.

PMID- 17227612
TI  - Developing needs-assessment tools for e-learning initiatives in preventive
      medicine in Pakistan.

PMID- 17227613
TI  - Reasoning and dyslexia: a spatial strategy may impede reasoning with visually
      rich information.
AB  - Bacon, Handley, and Newstead (2003, 2004), have presented evidence for individual
      differences in reasoning strategies, with most people seeming to represent and
      manipulate problem information using either a verbal or a spatial strategy. There
      is also evidence that individuals with dyslexia are inclined to conceptualise
      information in a visuo-spatial, rather than a verbal, way (e.g. von Karolyi et
      al., 2003). If so, we might expect a higher proportion of individuals with
      dyslexia to be spatial reasoners, compared with individuals who do not have
      dyslexia. The study reported here directly compared strategies reported by these
      two groups of participants on a syllogistic reasoning task. Moreover, problem
      content was manipulated so that reasoning across concrete and abstract materials
      could be compared. The findings suggest that whilst most individuals without
      dyslexia use a verbal strategy, reasoners with dyslexia do tend to adopt a
      spatial approach, though their performance is impaired with visually concrete
      materials. However, when reasoning with more abstract content, they perform
      comparably with non-dyslexic controls. The paper discusses these results in the
      light of recent research which has suggested that visual images may impede
      reasoning, and considers how individuals with dyslexia may differ from other
      reasoners.

PMID- 17227615
TI  - Targeting nitric oxide for cancer therapy.
AB  - A blueprint for the ideal anticancer molecule would include most of the
      properties of nitric oxide (NO*), but the ability to exploit these
      characteristics in a therapeutic setting requires a detailed understanding of the
      biology and biochemistry of the molecule. These properties include the ability of
      NO* to affect tumour angiogenesis, metastasis, blood flow and immuno
      surveillance. Furthermore NO* also has the potential to enhance both radio- and
      chemotherapy. However, all of these strategies are dependent on achieving
      appropriate levels of NO*, since endogenous levels of NO* appear to have a clear
      role in tumour progression. This review aims to summarize the role of NO* in
      cancer with particular emphasis on how the properties of NO* can be exploited for
      therapy.

PMID- 17227616
TI  - Evaluation of metered dose inhaler (MDI) formulations of ciclosporin.
AB  - Our purpose was to evaluate metered dose inhaler (MDI) formulations of
      cyclosporin (cyclosporine) for aerodynamic properties, chemical stability and
      bioactivity. Ciclosporin formulations (0.1, 0.5 and 1.0% w/w) were prepared in
      hydrofluoroalkane (HFA) propellants (134a and 227) containing 3 and 6% ethanol.
      Aerodynamic properties of the MDI formulations were analysed using an eight-stage
      Andersen cascade impactor and respirable mass and non-respirable mass, mass
      median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were
      determined from the impaction profiles. The chemical stability of 0.1%
      ciclosporin in HFA 227 containing 3% ethanol formulation stored at room
      temperature and 40 degrees C was evaluated by HPLC at 0, 14, 30 and 90 days. The
      bioactivity of ciclosporin MDI formulations was evaluated by determining the
      ciclosporin-mediated inhibition of interleukin-2 (IL-2) release from human Jurkat
      cells stimulated with phorbol 12-myristate 13-acetate (PMA). As ethanol
      concentration increased from 3 to 6%, respirable mass decreased from 2.3 mg per
      five actuations to 0.04 mg per five actuations for HFA 227 formulations, and from
      1.5 mg to 0.09 mg per five actuations for HFA 134a formulations. The MMAD for
      both HFA 134a and 227 formulations increased with an increase in ciclosporin
      concentration. HPLC analysis showed ciclosporin to be extremely stable in HFA 227
      at room temperature and 40 degrees C. Stimulation of Jurkat cells with PMA
      released significant amounts of IL-2, which was inhibited by ciclosporin in a
      dose-dependent manner. This study shows the feasibility of developing chemically
      stable and bioactive HFA-based MDI formulations of ciclosporin.

PMID- 17227617
TI  - The influence of non-disintegrating tablet dimensions and density on their
      gastric emptying in fasted volunteers.
AB  - The aim of this work was to identify the influence of tablet density on their
      gastric emptying in fasted subjects and to compare the findings with those of a
      previous study using the same subjects with tablets of a larger diameter. Tablets
      of 6.6 mm diameter and densities of 1.41 and 2.85 g cm-3 were labelled with 99mTc
      and 111In. They were coated with ethyl cellulose to ensure that they remained
      intact within the gastrointestinal tract. Their position within the
      gastrointestinal tract of fasted healthy subjects was monitored with a double
      headed gamma camera at 1-min time intervals. The median gastric emptying time and
      the interquartile range were derived from the Bernoulli random event
      distribution. It was found that the dense tablets had a significantly longer
      gastric emptying time than the light tablets. Comparison with the results from
      the previous study gave a clear indication that irrespective of tablet density,
      the 6.6-mm tablets had longer gastric emptying times than the 12.0-mm tablets.

PMID- 17227618
TI  - Modification of the crystal habit of celecoxib for improved processability.
AB  - Crystallization is often used in the pharmaceutical industry for purification and
      isolation of drugs, and also as a means of generating polymorphs or isomorphs.
      The aim of this study was to investigate the role of extrinsic crystallization
      parameters on the crystallized product, with special emphasis on improving the
      mechanical properties of acicular celecoxib. Celecoxib isomorphs were prepared
      using different techniques (solvent crystallization and vapour diffusion) and
      crystallization conditions (solvents, stirring, degree of supersaturation,
      crystallization temperature and seeding). Powder X-ray diffractometry,
      spectroscopic and thermal methods were used to investigate physical
      characteristics of crystals. Growth kinetics and aggregation dynamics of
      crystallization in polar and non-polar solvents were simulated using a dynamic
      light scattering method. The quick appearance of broad peaks over the range of 10
      8000 nm in chloroform during crystallization simulation studies indicated faster
      aggregation in non-polar solvents. Aspect ratio, flow, compressibility and
      surface area of recrystallized products were also determined. Surface topography
      was determined by atomic force microscopy and the lath-shaped crystals (aspect
      ratio of 2-4) exhibited a roughness index of 1.79 in comparison with 2.92 for
      needles. Overall, the lath-shaped isomorphs exhibited improved flow and better
      compressibility.

PMID- 17227619
TI  - Topical buparvaquone formulations for the treatment of cutaneous leishmaniasis.
AB  - As the part of a study to develop buparvaquone (BPQ) formulations for the
      treatment of cutaneous leishmaniasis, the topical delivery of BPQ and one of its
      prodrugs from a range of formulations was evaluated. In previous studies, BPQ and
      its prodrugs were shown to be potent antileishmanials in-vitro, with ED50 values
      in the nanomolar range. 3-Phosphono-oxymethyl-buparvaquone (3-POM-BPQ) was the
      most potent antileishmanial and was chosen, together with the parent drug, for
      further investigation. The ability of the parent and prodrug formulations to
      cross human and murine skin was tested in-vitro using the Franz diffusion cells.
      Formulations intended for topical application containing either BPQ or 3-POM-BPQ
      were developed using excipients that were either acceptable for topical use (GRAS
      or FDA inactive ingredients) or currently going through the regulatory process.
      BPQ was shown to penetrate both human epidermal membranes and full thickness
      BALB/c skin from a range of formulations (gels, emulsions). Similarly, 3-POM-BPQ
      penetrated full-thickness BALB/c skin from several gel formulations. In-vitro
      binding studies showed that BPQ bound melanin in a dose-dependent manner and
      preferably bound to delipidized skin over untreated BALB/c skin (on a weight to
      weight basis). The results confirm that BPQ and its prodrug 3-POM-BPQ can
      penetrate the skin from several formulations, making them potentially interesting
      candidates for further investigation of topical formulations using in-vivo models
      of cutaneous leishmaniasis.

PMID- 17227620
TI  - Image analysis by pulse coupled neural networks (PCNN)--a novel approach in
      granule size characterization.
AB  - A biologically inspired spiking neural network model, the pulse coupled neural
      network (PCNN), has been applied for the first time in bulk particle
      characterization, and specifically in the characterization of pharmaceutical
      granule size distributions. The PCNN was trained on surface images of
      pharmaceutical granule beds, and the adjustable parameters (radius neuron
      interconnection, r0, linking weight coefficient, beta, local threshold potential,
      VTheta, and number of iterations) were successfully optimized using design of
      experiments. As demonstrated with size fractions of granules, it was found that
      the PCNN produced granule size-dependent signals. In general, a first highest and
      relatively narrow peak located in the region of two to twelve iterations
      corresponded to smaller particle size, while larger particles resulted in wider
      peaks and in highest (not first) peak at a range between 13 and 25 iterations.
      Better predictions, i.e. lower RMSEP (root mean squared error of prediction)
      values, were obtained using high beta value, low r0 and VTheta values, while the
      number of iterations had to exceed 110 and the optimized model (RMSEP lower than
      5) corresponded to PCNN variables: r0=1, beta=0.4, VTheta=2, and number of
      iterations=150. The coefficient of determination (R2) of the model was 0.94 and
      the predicted variation (Q2) was 0.91, while the Pearson correlation coefficient
      between the predicted and the measured mean particle size by sieving for eight
      test batches was 0.98. These findings could be characterized as promising and
      encouraging for the further use of image analysis by PCNNs in pharmaceutical bulk
      particle size and shape characterization.

PMID- 17227621
TI  - Enteric-coated solid dosage forms containing sodium bicarbonate as a drug
      substance: an exception from the rule?
AB  - Sodium bicarbonate (sodium hydrogen carbonate) is used as an oral medication in
      disorders such as mild metabolic acidosis and chronic kidney disease. The two
      commercial products on the German market, bicaNorm and Nephrotrans, and also
      newly developed multiple-unit pellet formulations, have been characterized in
      these investigations by in-vitro methods like disintegration and dissolution
      testing. Both marketed products containing sodium bicarbonate are of sufficient
      pharmaceutical quality according to the European Pharmacopoeia. However, they and
      the novel pellet preparations showed different drug release at moderately
      elevated pH values. Early drug release may cause dose dumping in the stomach and
      adverse drug effects from the developed carbon dioxide. The soft capsule
      preparation (Nephrotrans) released the smallest amount of sodium bicarbonate at
      pH 1 and 4.5 of all formulations tested. It appeared that oral dosage
      formulations of sodium bicarbonate were an exception to the rule: the monolithic
      soft capsule seemed to be superior to an enteric-coated tablet as well as to
      multiple-unit pellet formulations from the biopharmaceutical point of view. Our
      results correspond with individual reports on adverse effects from patients
      treated with the sodium bicarbonate products.

PMID- 17227622
TI  - Involvement of alpha1-acid glycoprotein in inter-individual variation of
      disposition kinetics of ropivacaine following epidural infusion in off-pump
      coronary artery bypass grafting.
AB  - The influence of drug interaction and protein variants on the binding disposition
      of ropivacaine to alpha1-acid glycoprotein (AGP) was examined. The subjects were
      five patients who received epidural infusion of ropivacaine for 24-54 h in off
      pump coronary artery bypass grafting followed by drug combination therapy, and 10
      healthy volunteers. The post-operation plasma albumin concentration showed little
      overall change, while the AGP concentration in the five patients decreased for 6
      h, then increased gradually to about 3-times the initial value by 54 h. The
      unbound fraction in plasma (fu) of ropivacaine gradually decreased as the AGP
      concentration increased, but there was large inter-individual variation among the
      five patients. In contrast, there was a good correlation between the fu value and
      AGP concentration when ropivacaine was added to blood samples from the 10 healthy
      volunteers. Among the volunteers, eight showed F1S variants and two showed F1
      variant without S variant of AGP. The fu value of ropivacaine did not differ
      between these two groups. However, when ropivacaine was added in combination with
      dipyridamole, the fu values of ropivacaine in blood from volunteers with F1S
      variants were greater than those in blood from volunteers without S variant. In
      the case of co-administration of disopyramide or lidocaine, there was no such
      difference. Among the patients, one showed F1S variants and four showed F1
      variant without S variant. The results indicate that variability in the side
      effects of therapy with ropivacaine alone is caused by the change of the unbound
      concentration upon changes in the AGP concentration. However, in combination
      therapy, it is also important to consider the AGP variant-dependence of the
      inhibitory effect of concomitantly administered drugs.

PMID- 17227623
TI  - Uptake characteristics of liposomes by rat alveolar macrophages: influence of
      particle size and surface mannose modification.
AB  - The influence of particle size and surface mannose modification on the uptake of
      liposomes by alveolar macrophages (AMs) was investigated in-vitro and in-vivo.
      Non-modified liposomes of five different particle sizes (100, 200, 400, 1000 and
      2000 nm) and mannosylated liposomes with 4-aminophenyl-alpha-D-mannopyranoside
      (particle size 1000 nm) were prepared, and the uptake characteristics by rat AMs
      in-vitro and in-vivo were examined. The uptake of non-modified liposomes by rat
      AMs in-vitro increased with an increase in particle size over the range of 100
      1000 nm, and became constant at over 1000 nm. The uptake of non-modified
      liposomes by AMs after pulmonary administration to rats in-vivo increased with an
      increase in particle size in the range 100-2000 nm. The uptake of mannosylated
      liposomes (particle size 1000 nm) by rat AMs both in-vitro and in-vivo was
      significantly greater than that of non-modified liposomes (particle size 1000
      nm). The results indicate that the uptake of liposomes by rat AMs is dependent on
      particle size and is increased by surface mannose modification.

PMID- 17227625
TI  - Efflux of baicalin, a flavone glucuronide of Scutellariae Radix, on Caco-2 cells
      through multidrug resistance-associated protein 2.
AB  - Baicalin and its aglycone, baicalein, being are strong antioxidants and have
      various pharmacological actions. Baicalein has shown a unique metabolic fate in
      rat intestine, being excreted into the intestinal lumen from mucosal (epithelial)
      cells following glucuronidation of baicalein absorbed after oral administration.
      The purpose of this study was to examine the absorption and excretion of baicalin
      and baicalein in a Caco-2 cell monolayer model to evaluate the disposition of
      baicalin and baicalein in the human intestine. When baicalein at 5 microM was
      loaded on the apical side of the Caco-2 cell monolayer, baicalein was not
      transferred to the basolateral side, but more baicalin was excreted onto the
      apical side than was being absorbed onto the basolateral side. The amount of
      baicalin recovered on both sides accounted for more than 90% of the baicalein
      absorbed from the apical surface. This was supported by the fact that Caco-2 cell
      microsomes showed UDP-glucuronate glucuronosyltransferase activity towards
      baicalein to form baicalin. On the other hand, when baicalein was loaded at
      higher concentrations, baicalin excretion became saturated, and then baicalein
      was transferred to the basolateral side. Furthermore, baicalin efflux was not
      inhibited by MDR1/P-glycoprotein substrates such as ciclosporin and vinblastine,
      but significantly inhibited by multidrug resistance-associated protein 2 (MRP2,
      ABCC2) substrates such as probenecid and genistein. MRP2 was also detected in
      Caco-2 cells by Western blotting using specific antibodies. In addition,
      baicalin, but not baicalein, enhanced dose-dependently the vanadate-sensitive
      ATPase activity of human MRP2. These results indicated that, in Caco-2 cells, any
      baicalein absorbed after loading at low concentrations of baicalein was not
      transferred to the basolateral side, but was first transformed into baicalin in
      the cells and excreted through the action of MRP2, mainly to the apical side.

PMID- 17227624
TI  - Ellagic acid peracetate is superior to ellagic acid in the prevention of
      genotoxicity due to aflatoxin B1 in bone marrow and lung cells.
AB  - Earlier observations carried out in our laboratory highlighted the mode of action
      of acetoxy 4-methylcoumarins and quercetin pentaacetate in preventing the
      genotoxicity of aflatoxin B1 (AFB1). We have extended the observation to an
      acetoxy biscoumarin i.e. ellagic acid peracetate (EAPA), which unlike ellagic
      acid (EA) has demonstrated time-dependent inhibition of liver microsomes
      catalysed AFB1-epoxidation as measured by AFB1 binding to DNA. EAPA was more
      potent than EA in preventing bone marrow and lung cells from AFB1-induced
      genotoxicity. EAPA was acted upon by microsomal acetoxy drug:protein
      transacetylase (TAase) leading to modulation of the catalytic activity of certain
      functional proteins (cytochrome P450, NADPH cytochrome c reductase and
      glutathione S-transferase), possibly by way of protein acetylation.

PMID- 17227626
TI  - Shifts in metabolic parameters surrounding glucose homoeostasis resulting from
      tricyclic antidepressant therapy: implications of insulin resistance?
AB  - This study displayed the physiological effects the tricyclic antidepressants
      amitriptyline or trimipramine have on glucose homoeostasis in male Wistar rats.
      An insulin secreting cell line (INS-1) was also used to determine effects
      tricyclic antidepressants have on insulin secretion and insulin displacement.
      Thirty rats each received a 1 mg kg-1 dose of amitriptyline or trimipramine for a
      period of 14 weeks; another 14 rats served as the control group. Blood glucose,
      serum insulin and muscle and liver glycogen levels were determined. Kidney, liver
      and muscle insulin degradation was measured and compared with insulin degrading
      enzyme concentrations in the latter two tissues. INS-1 cells were used to
      determine the effect 1 microM amitriptyline has on insulin secretion.
      Displacement studies for [3H]glibenclamide by amitriptyline or trimipramine were
      undertaken on INS-1 cells. A significant increase in blood glucose (P<0.01) was
      found for both test groups after 6 and 14 weeks of receiving the medication,
      which may be related to a significant decrease in liver and muscle glycogen
      levels (P<0.001). Serum insulin levels remained unchanged, although a significant
      increase in insulin degradation was observed in the muscle, liver and kidney,
      which may be related to a significant increase in insulin degrading enzyme
      (P<0.001) that was found. A significant increase in insulin secretion was
      observed for the INS-1 cells treated with amitriptyline, although no significant
      displacement for the [3H]glibenclamide was evident for amitriptyline or
      trimipramine. The significant alterations in glucose homoeostasis observed, as
      well as the significant changes associated with insulin secretion and degradation
      associated with amitriptyline or trimipramine treatment, imply that prolonged use
      of these medicines may lead to insulin resistance and full blown diabetes.

PMID- 17227627
TI  - Enantioselectivity of thalidomide serum and tissue concentrations in a rat glioma
      model and effects of combination treatment with cisplatin and BCNU.
AB  - Thalidomide is currently under evaluation as an anti-angiogenic agent in cancer
      treatment, alone and in combination with cytotoxic agents. Thalidomide is a
      racemate with known pharmacologic and pharmacokinetic enantioselectivity. In a
      previous study with thalidomide combination chemotherapy, we found evidence of
      anti-tumour synergy. In this study, we examined whether the synergy involved
      altered pharmacokinetics of thalidomide enantiomers. Adult female F344 rats were
      implanted with 9L gliosarcoma tumours intracranially, subcutaneously (flank), or
      both. Effectiveness of oral thalidomide alone, and with intraperitoneal BCNU or
      cisplatin combination chemotherapy, was assessed after several weeks treatment.
      Presumed pseudo steady-state serum, tumour and other tissues, collected after
      treatment, were assayed for R- and S-thalidomide by chiral HPLC. Both serum and
      tissue concentrations of R-thalidomide were 40-50% greater than those of S
      thalidomide. Co-administration of BCNU or cisplatin with thalidomide did not
      alter the concentration enantioselectivity. Poor correlation of concentration
      with subcutaneous anti-tumour effect was found for individual treatments, and
      with all treatments for intracranial tumours. The consistency of the enantiomer
      concentration ratios across treatments strongly suggests that the favourable
      antitumour outcomes from interactions between thalidomide and the cytotoxic
      agents BCNU and cisplatin did not have altered enantioselectivity of thalidomide
      pharmacokinetics as their basis.

PMID- 17227628
TI  - The protective action of scutellarin against immunological liver injury induced
      by concanavalin A and its effect on pro-inflammatory cytokines in mice.
AB  - Scutellarin is a natural compound from a Chinese herb. The purpose of this paper
      was to study the protective effect of scutellarin on concanavalin A (Con A)
      induced immunological liver injury and its effect on liver nuclear factor kappaB
      (NF-kappaB), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN
      gamma), and inducible nitric oxide synthase (iNOS) expression in mice. Mouse
      liver injury was produced by injection of Con A 25 mg kg-1 via the tail vein.
      Scutellarin 50 or 100 mg kg-1 was peritoneally administered to mice 9 or 1 h
      before injection of Con A. The levels of serum alanine aminotransferase (ALT) and
      asparatate aminotransferase (AST), NO2-/NO3- and TNF-alpha were determined with
      biochemical kits, and ELISA using Quantikine Mouse TNF-alpha kit according the
      manufacturer's instructions. Liver lesions were examined by light microscope. The
      expression of TNF-alpha, IFN-gamma, iNOS and Fas mRNA in the livers was detected
      by RT-PCR; and the expression of c-Fos, c-Jun, iNOS and IkappaB proteins was
      measured by Western Blotting. As a result, pretreatment with scutellarin 100 mg
      kg-1 significantly decreased the serum ALT, AST, NO2-/NO3- and TNF-alpha levels,
      and also reduced liver lesions induced by Con A. Scutellarin 100 mg kg-1 down
      regulated expression of TNF-alpha and iNOS mRNA, and c-Fos, c-Jun and iNOS
      protein, while scutellarin enhanced the degradation of IkappaB in the livers of
      mice injected with Con A. The results suggest that scutellarin has a protective
      action against Con A-induced liver injury in mice, and its active mechanism may
      be related to the inhibition of the NF-kappaB-TNF-alpha-iNOS transduction
      pathway.

PMID- 17227629
TI  - In-vitro and in-vivo anti-inflammatory action of the ethanol extract of
      Trachelospermi caulis.
AB  - In this study, we aimed to investigate the anti-inflammatory activity,
      antinociceptive activity and the action mechanism of Trachelospermi caulis
      extract. The anti-inflammatory effects were investigated using arachidonic acid,
      12-O-tetradecanoylphorbol 13-acetate or carrageenan-induced oedema assays.
      Antinociceptive activity, using the acetic acid-induced writhing model, was also
      tested in mice. The extract exhibited dose-dependent and significant (P<0.05 at
      100-400 mg kg-1) anti-inflammatory and antinociceptive activity in the animals.
      To further understand the mechanism of activity, we investigated whether the
      extract inhibited the expression of inducible nitric oxide synthase (iNOS), the
      production of nitric oxide (NO) and the expression of TNF-alpha from murine
      macrophage RAW 264.7 cells. Similar to the in-vivo activity, the iNOS expression,
      NO production and TNF-alpha expression were found to be dose dependent and
      significantly suppressed by the extract through the inhibition of the p38 MAP
      kinase/NF-kappaB pathway. Taken together, the results presented here suggest that
      T. caulis extract may be useful for the treatment of various inflammatory
      diseases.

PMID- 17227630
TI  - Study of potential systemic oxidative stress animal models for the evaluation of
      antioxidant activity: status of lipid peroxidation and fat-soluble antioxidants.
AB  - Although many compounds have already been tested in-vitro to determine their
      antioxidant profile, it is necessary to investigate the in-vivo effect of
      potential antioxidants. However, representative models of systemic oxidative
      stress have been poorly studied. Here, different potential systemic oxidative
      stress animal models have been investigated. These included a vitamin E-deficient
      rat, a diabetic rat and an atherosclerotic rabbit model. Plasma/serum
      malondialdehyde was measured as a parameter of oxidative damage. Plasma/serum fat
      soluble antioxidants were determined as markers of antioxidant defence. We
      demonstrated that vitamin E-deficient rats were not suitable as a model of
      systemic oxidative stress, whereas diabetic and atherosclerotic animals showed
      increased systemic oxidative damage, as reflected by significantly augmented
      plasma/serum malondialdehyde. Moreover, plasma coenzyme Q9 increased by 80% in
      diabetic rats, confirming systemic oxidative stress. In view of these
      observations and economically favouring factors, the diabetic rat appeared to be
      the most appropriate systemic oxidative stress model. These findings have
      provided important information concerning systemic oxidative stress animal models
      for the in-vivo study of antioxidants.

PMID- 17227631
TI  - Prednisolone phosphate-containing TRX-20 liposomes inhibit cytokine and chemokine
      production in human fibroblast-like synovial cells: a novel approach to
      rheumatoid arthritis therapy.
AB  - To evaluate the potential of using prednisolone phosphate (PSLP)-containing 3,5
      dipentadecyloxybenzamidine hydrochloride (TRX-20) liposomes to treat rheumatoid
      arthritis (RA), we examined their ability to bind human fibroblast-like synovial
      (HFLS) cells and their effects in these cells. To test for binding, Lissamine
      rhodamine B-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (rhodamine)
      labelled PSLP-containing TRX-20 liposomes were added to HFLS cells, and the
      fluorescence intensity of the rhodamine bound to the cells was evaluated.
      Rhodamine-labelled PSLP-containing liposomes without TRX-20 were used as a
      negative control. To evaluate the uptake of liposomes by the HFLS cells, we used
      TRX-20 liposomes containing 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) and p
      xylene-bis-pyridinium bromide (DPX), and observed the cells by fluorescence
      microscopy. The effects of the PSLP in TRX-20 liposomes on HFLS cells were
      assessed by the inhibition of the production of two inflammatory cytokines
      (interleukin 6 and granulocyte macrophage colony-stimulating factor) and one
      inflammatory chemokine (interleukin 8). The interaction of the PSLP-containing
      TRX-20 liposomes with HFLS cells was approximately 40 times greater than that of
      PSLP-containing liposomes without TRX-20. PSLP-containing TRX-20 liposomes bound
      to HFLS cells primarily via chondroitin sulfate. TRX-20 liposomes taken up by the
      cell were localized to acidic compartments. Furthermore, the PSLP-containing TRX
      20 liposomes inhibited the production of the inflammatory cytokines and the
      chemokine more effectively than did the PSLP-containing liposomes without TRX-20.
      These results indicate that PSLP-containing TRX-20 liposomes show promise as a
      novel drug delivery system that could enhance the clinical use of glucocorticoids
      for treating RA.

PMID- 17227632
TI  - Cancer screening in Asia.

PMID- 17227633
TI  - Multistate and multifactorial progression of gastric cancer: results from
      community-based mass screening for gastric cancer.
AB  - Although multistate progression models for gastric cancer have been proposed,
      estimation of quantitative parameters of such models is yet to be done. The
      present study was conducted to elucidate risk factors for gastric cancer and its
      precursors, and to model the progression rates from superficial gastritis to
      gastric cancer. Data were derived from a community-based screening programme for
      gastric cancer in the Matzu region of Taiwan. A total of 2184 residents
      participated in a two-stage screening project. Subjects testing positive for
      Helicobacter pylori infection or pepsinogen (PGI or PII/PGII ratio) and
      immunoglobulin G (IgG), and subjects with a history of peptic ulcer or other
      upper gastrointestinal disease or with a family history of gastric cancer were
      referred to endoscopy. We identified 325 biopsy-proven precursors and gastric
      cancers, including 148 superficial gastritis (SG), 42 atrophic gastritis (AG),
      117 intestinal metaplasia (IM) and two gastric cancers. Three further cancers
      were diagnosed on endoscopy alone and 14 were later diagnosed in those who did
      not comply with referral to endoscopy. A Markov process model was used to
      estimate the progression rates from superficial gastritis through to gastric
      cancer, with exponential regression to assess the effect of covariates on
      progression rates. The annual progression rate from SG to AG was 0.0670 (95%
      confidence interval [CI] 0.0446-0.0895). Annual progression rates from AG to IM
      and from IM to gastric cancer were 0.2775 (0.1665-0.3884) and 0.2265 (0.1315
      0.3214), respectively. This gives average dwelling times in AG and IM of 3.60
      years and 4.42 years, respectively. Progression from no disease to SG was
      significantly accelerated in those testing positive for H. pylori, those testing
      positive for PGI and in subjects with a family history of gastric cancer or a
      personal history of upper gastrointestinal disease. Further progression to AG and
      IM was significantly accelerated in those testing positive for PGI and in those
      with a history of upper gastrointestinal disease.

PMID- 17227634
TI  - Colorectal cancer screening using immunochemical faecal occult blood testing in
      Japan.
AB  - Japan has had a programme of colorectal cancer screening with immunochemical
      faecal occult blood testing since 1992. Participation rates are around 17%.
      Approximately 7% of subjects test positive and, of these, around 60% comply with
      the request to undergo further diagnostic testing. Colorectal cancer rates have
      been increasing rapidly in Japan in recent decades, and there is an urgent need
      to improve participation rates.

PMID- 17227635
TI  - Colorectal cancer screening with faecal occult blood test within a multiple
      disease screening programme: an experience from Keelung, Taiwan.
AB  - BACKGROUND: Given increasing rates of colorectal cancer (CRC) in countries with
      intermediate incidence rates, the decision to implement population-based
      screening must consider the trade-off between high costs and a relatively low
      yield. In Taiwan, we proposed community-based CRC screening using faecal occult
      blood tests (FOBT) within a multiple disease screening programme. AIMS: Based on
      early results from the screening programme, we aimed to compare the projected
      efficacies, in terms of reductions in CRC mortality, achieved with multiple
      disease screening, single disease screening and no screening programmes. METHODS:
      Annual FOBT has been included in the Keelung multiple disease screening
      programme. A total of 26,008 subjects were offered screening. Early indicators
      have been estimated to assess the potential effectiveness of this programme,
      including the Dukes' stage distribution of screen-detected cases, the
      proportionate incidence and the prevalence/incidence ratio. Transition rates
      according to adenoma size and Dukes' stage have been estimated from an eight
      state Markov model. The projected mortality reductions based on this disease
      natural history have been estimated using Markov Chain Monte Carlo simulation for
      both multiple screening and single screening. RESULTS: The overall attendance
      rate was 82% at the first screen and 87% at the second screen. At the first
      screen, 70% of screen-detected cases were localized (i.e. Dukes' stage A or B).
      The corresponding figure for the second screen was 80%. Approximately three
      quarters of detected adenomas were smaller than 1 cm. The estimated mean
      transition times from diminutive adenoma to small adenoma, from small adenoma to
      large adenoma and from large adenoma to pre-clinical Dukes' A or B invasive
      carcinoma were 14.4, 5.4 and 5.6 years, respectively. Estimated reductions in CRC
      mortality, based on annual screening, are 23 and 33% for the single and multiple
      disease screening programmes, respectively. Multiple screening with an annual
      screening regime may lead to a further 13% reduction in mortality when compared
      to conventional single screening. CONCLUSION: Early indications suggest that
      population-based screening for CRC with FOBT, implemented through a multi-disease
      screening programme, is both feasible and efficacious. Further evaluation of the
      programme, through longer follow-up and cost-effectiveness analysis, is now
      required.

PMID- 17227637
TI  - Breast, stomach and colorectal cancer screening in Korea.
AB  - Some issues and activities in cancer screening in Korea are briefly described, in
      particular those in stomach, breast and colorectal screening. There is randomized
      trial evidence for the efficacy of screening for breast cancer and colorectal
      neoplasia. Stomach cancer screening is as yet unproven, but the disease is very
      common in Korea and one of the leading causes of death. There are major related
      issues to be addressed by the country in the near future. These include improving
      uptake and coverage rates, quality control and evaluation. Colorectal cancer will
      be a major concern as its incidence and mortality rates have been increasing
      rapidly in recent years.

PMID- 17227636
TI  - Cancer screening in Singapore, with particular reference to breast, cervical and
      colorectal cancer screening.
AB  - Cancer is the leading cause of mortality in Singapore, accounting for 27.1% of
      deaths in 2004. The most common cancers are those of the lung, colon and rectum,
      liver, stomach, and prostate in men; and breast, colon and rectum, lung, ovary
      and cervix in women. Singapore has the highest age-adjusted breast cancer
      incidence in Asia. National population screening programmes have been implemented
      for breast and cervical cancer. BreastScreen Singapore (BSS), the first
      population-based nationwide mammographic breast-screening programme in Asia, was
      launched in 2002, incorporating international standards and practice guidelines.
      For improved quality assurance, two-view screening mammography is carried out.
      From January 2002 until March 2004, BSS conducted over 84,000 screens, with an
      overall recall rate of 9.5%, and an overall invasive cancer detection rate of
      4.48 per 1000 screened. Close to 30% of the cancers diagnosed was ductal
      carcinoma in situ. Papanicolaou (Pap) smear screening for cervical cancer has
      been available opportunistically since 1964. The national CervicalScreen
      Singapore programme was launched in 2004, aiming to achieve coverage of 80% of
      targeted women by 2010. Colorectal cancer currently has the highest incidence of
      all cancers in Singapore. The health authorities advocate colorectal cancer
      screening for the average risk population, starting from age 50 years, but in the
      absence of a national screening programme, the reliance is on opportunistic
      screening.

PMID- 17227638
TI  - Evolution of breast cancer screening in countries with intermediate and
      increasing incidence of breast cancer.
AB  - BACKGROUND: Few studies have been published regarding the practice of breast
      cancer screening in Asian countries. AIMS: The present study illustrates how the
      health policy for breast cancer screening has evolved in Taiwan from selective
      mammographic screening within a high-risk group, firstly to a programme of
      physical examination by public health nurses, and finally to a two-stage breast
      cancer screening programme, with a risk assessment followed by mammography for
      those at moderate to high risk. DATA SOURCES: Breast cancer screening has evolved
      from 1995 to 2004 in Taiwan in three stages: (1) selective screening for breast
      cancer with mammography, ultrasound and physical examination only in first-degree
      relatives of breast cancer cases (1995-1998); (2) a programme of mass screening
      (1999-2001) with physical examination by public health nurses; and (3) two-stage
      breast cancer screening with a risk factor questionnaire and mammography for
      those deemed at moderate-to-high risk (2002-2004). The questionnaire was based on
      significant risk factors in a previous epidemiological study, in conjunction with
      the physical examination programme, a risk score was constructed from the
      logistic regression coefficients from the previous study, and women with a score
      above the median in the previous epidemiological study were assigned to
      mammography. RESULTS: Two-stage mammography screening had the most favourable
      results compared with the two previous screening regimes. It had a positive
      predictive value of recall after mammography of 14%, compared with 8% for
      selective screening and 2% for physical examination. Of screen-detected cancers
      in the two-stage programme, 71% were either ductal carcinoma in situ or stage T1,
      compared with 61% for selective screening and 60% for physical examination. The
      area under the receiver operating characteristic curve was 71% for the two-stage
      programme. CONCLUSIONS: For a low- to medium-risk country such as Taiwan, two
      stage screening has acceptable parameters of recall and cancer detection, and
      compares well with other screening strategies.

PMID- 17227639
TI  - Some issues in screening for breast and other cancers.
AB  - BACKGROUND: There are some issues in screening for cancer, especially breast
      cancer, which are worthy of further study. METHODS: We reviewed some approaches
      to the following issues in breast cancer screening: absolute benefit,
      overdiagnosis, separation of effects of screening from effects of others on
      deaths from breast cancer over time and determination of which tumours benefit
      most from early detection. For separation of screening effects from other
      effects, we developed a simple analysis of survival by tumour size. For the other
      issues, we identified methods and results from the literature on the randomized
      trials of screening and on service screening programmes. We also reviewed
      screening issues pertaining to other selected cancers, including some cancers
      common or becoming common in Asia. RESULTS: Published results from the Swedish
      Two-County Trial showed that for 350 women screened for 10 years, one life would
      be saved. Results from service screening programmes in Florence and elsewhere
      suggested that overdiagnosis is a minor phenomenon and mainly confined to ductal
      carcinoma in situ. Data from before and after the inception of screening in East
      Anglia suggested that 40-60% of the recent improvement in survival of breast
      cancer cases was due to early detection. Published data from the Swedish Two
      county Trial indicated that the majority of the benefit of breast screening
      derives from early detection of grades 2 and 3 ductal carcinoma. CONCLUSIONS:
      Mammographic screening is effective in saving lives from breast cancer. Other
      cancers, which have strong evidence for a benefit of screening in terms of saving
      lives from cancer, are cervical and colorectal cancers. There is also evidence of
      a reduction in mortality associated with ultrasound screening for liver cancer in
      subjects at very high risk of the disease. There are a number of other cancers
      that are potential candidates for early detection. There is clearly an
      opportunity for saving lives from further development and implementation of
      cancer screening.

PMID- 17227640
TI  - Cervical and oral cancer screening in India.
AB  - Incidence of both cervical and oral cancer are high in India. Although there are
      no organized cervical or oral screening programmes in the country, a number of
      research projects are ongoing or recently completed. In cervical screening, a
      number of studies of visual inspection with various aids and studies of human
      papillomavirus (HPV) testing are in progress. Long-term follow-up of these will
      inform policy on cervical screening in limited resource countries. A randomized
      trial of oral visual inspection for cancer or premalignant lesions in 192,053
      subjects has been conducted in Kerala, South India. In the trial population as a
      whole, the study group showed a non-significant 21% reduction in mortality from
      oral cancer compared with the control group. In users of alcohol, tobacco or
      both, in which more than 90% of oral cancer deaths occurred, the reduction was a
      significant 34% (relative risk = 0.66, 95% confidence interval 0.45-0.95). On the
      basis of these results, screening for oral abnormalities has the potential to
      prevent 37,000 deaths per year worldwide.

PMID- 17227641
TI  - Cervical cancer screening in Thailand: an overview.
AB  - In Thailand, there have been no 'organized' programmes of screening for cervical
      cancer. For the most part, screening has been unsystematic or provided to women
      'on demand'. In 2002, the Department of Medical Services of the Ministry of
      Public Health proposed the screening of the entire population of women in
      Thailand at 5-yearly intervals from the ages of 35 to 60 years. As a first step,
      measures to increase the capacity for obtaining and interpreting papanicolaou
      (Pap) smears have been put in place. Research studies have examined the
      effectiveness of screening with Pap smears in Thailand, and confirmed that, as
      elsewhere, protection is related to the number of previous tests and the time
      elapsed since the most recent one. Coverage of the population remains low. Other
      methods of screening are being investigated in Thailand, including visual
      inspection following acetic acid (VIA), followed by immediate treatment of
      observed lesions by cryotherapy ('see and treat'). Other research studies have
      examined the acceptability and performance of self-sampling as a means of
      obtaining Pap smears, and the use of mobile clinics to increase coverage of at
      risk women in rural settings. Human papillomavirus (HPV) testing has been used to
      identify high-risk women, or to help decide which women with low-grade
      abnormality on cytology should undergo more intensive follow-up. Prevalence of
      HPV in normal women in Thailand is 9-20%, but HPV testing has not been used on
      any systematic basis to date. Current screening programmes in Thailand are not
      very effective. The national cancer control programme aims to increase the
      coverage of screening. The population-based cancer registry will provide an
      effective and economical method of evaluating the impact of early diagnosis and
      screening at community level.

PMID- 17227642
TI  - Efficacy and cost-effectiveness of nationwide cervical cancer screening in
      Taiwan.
AB  - The annual cervical screening programme using the Papanicolaou (Pap) smear test
      was launched for women aged 30 years and over from 1995 in Taiwan. This study
      aimed to evaluate the Taiwanese cervical screening policy and to make
      recommendations based on the empirical findings from cervical screening data
      between 1995 and 1998. We used a stochastic process to model the natural history
      of precancerous lesions and cervical cancer. Based on the estimated results,
      Monte-Carlo computer simulation was used to evaluate the effectiveness in terms
      of the reduction in incidence of and mortality from cervical cancer for screening
      regimes with different screening intervals. Annual Pap smear screening with 100%
      compliance was estimated to lead to an approximate 80% reduction in deaths from
      cervical cancer. With 50% compliance, around a 40% reduction was expected.
      Triennial screening with high compliance was as effective as annual screening
      with low compliance, and more cost-effective. Based on the observed Taiwan Pap
      smear-screening programme between 1995 and 1998, with 44.5% women attending at
      least once, there was an estimated reduction of 16% in deaths from cervical
      carcinoma. The estimated effectiveness was greater when the period was extended
      to 2001, in which period 61% of women attended at least once. The screening
      programme by 2001 was estimated to reduce cervical cancer mortality by 50% (95%
      confidence interval: 29-65%). The incremental cost-effectiveness was estimated as
      8174 dollars per additional life-year gained. In conclusion, triennial screening
      targeting women aged 30-69 is recommended, along with efforts to enhance the
      compliance rate.

PMID- 17227643
TI  - Cancer screening in the USA.
AB  - Once screening for cancer has been shown to be effective, reducing cancer
      morbidity and mortality in the population depends on the successful delivery of
      mass screening. Today, screening for cancer may be achieved through the organized
      delivery of services, or unsystematically, by individual referral for screening
      at intervals which are not necessarily optimal or regularly spaced. Organized
      screening is distinguished from unsystematic screening primarily on the basis of
      how the offer of screening occurs--whether by invitation, issued from centralized
      population registers or coincidently, depending on individuals seeking screening
      on their own, or having providers initiate screening during visits for care for
      other reasons. This manuscript describes cancer screening in the USA, which for
      most Americans is unsystematic. While this model can achieve many of the goals of
      screening, these goals are achieved at a greater cost, less efficiently, and
      without the assurance of full participation of the entire, eligible population.
      In order to achieve the fullest potential of cancer screening in the most cost
      effective manner, screening should be organized, with attention to monitoring the
      fullest performance of the programme from recruitment to follow-up.

PMID- 17227644
TI  - Evolution of multiple disease screening in Keelung: a model for community
      involvement in health interventions?
AB  - OBJECTIVE: Screening for cancer and other chronic conditions tends to be
      conducted in independent programmes; that is, screening for one disease at a
      time. The Keelung community-based multiple disease screening programme, developed
      in Keelung city, Taiwan, is a notable exception. Here, we report on the Keelung
      programme's ethos and development within the community, focusing on equity of
      delivery of the service, and community involvement. In addition, we present some
      preliminary cost-effectiveness analyses of multiple disease screening. METHODS:
      The Keelung programme offers screening for breast, colorectal and liver cancers,
      cervical and oral neoplasia, all of which have an evidence base for their
      efficacy, and for diabetes, hypertension, osteoporosis and hyperlipidaemia, which
      are of unknown efficacy. We assessed variability of coverage rates of the Keelung
      Community-based Integrated Screening (KCIS) programme with age and socioeconomic
      status, availability of facilities for referral of positive screenees, and
      numbers of community social workers, general practitioners and local hospitals
      involved in the programme. We also assessed in qualitative terms how the
      programme interacts with non-health agencies. Finally, we simulated activities
      and costs for a variety of single- and multiple-disease screening situations.
      RESULTS: Between 1999 and 2003, coverage increased overall from 14.7 to 34.4%,
      and increased most dramatically in people aged 60-79 years (from around 30 to
      60%) and in those of lower educational status (from around 40 to 70%). There was
      a significant growth in the involvement of social workers and volunteers in the
      programme, and an increase in the availability of local diagnostic and care
      facilities for those screened positive. In addition, there was substantial
      involvement of non-health agencies in publicizing the programme. In the health
      economic simulations, compared with no screening, the extra costs to gain an
      additional life year were estimated as 667 US dollars, 608 US dollars, 4227 and
      4789 US dollars for multiple screening with 100% attendance, multiple screening
      with 70% attendance, single disease screening with 100% attendance and single
      disease screening with 30% attendance at each programme (i.e. 74% attendance for
      at least one out of four programmes), respectively. CONCLUSIONS: The innovative
      design and outreach procedures of the KCIS have led to a growth in delivery of
      screening services to groups sometimes overlooked (equity), community involvement
      in health care (participation) and the use of non-health organizations for
      publicity and health education (collaboration). Simulation studies indicate that
      multiple disease screening may be more cost-effective than single disease
      screening.

PMID- 17227646
TI  - The chequered history of malaria control: are new and better tools the ultimate
      answer?
AB  - Following Ronald Ross' demonstration in 1897 that mosquitoes transmit malarial
      parasites, efforts to control malaria were naturally focussed on attacking the
      mosquito vector by various measures, mainly directed against the aquatic stages.
      Although the results were spectacular in some areas, there was a growing
      realisation that effective control of malaria depended on other factors,
      including the availability of better drugs than quinine and a greater
      understanding of the epidemiology of the disease under various environmental
      conditions. With the discovery of DDT, an all-out effort was made to eradicate
      malaria by attacking adult mosquitoes. Eradication was not achieved in many
      countries, mainly because of inadequate health infrastructures. With the
      emergence of chloroquine-resistant parasites, the search for more effective drug
      regimens intensified, various drugs and drug combinations were assessed, and
      methods were developed to monitor and assess degrees of resistance. Since
      resistance to drugs can develop very quickly, the use of drug combinations,
      especially those containing artemisinin derivatives, is now recommended.
      Insecticide-impregnated bednets have become the preferred method of vector
      control. Although the search for better tools must continue, the events of the
      past century emphasise the need to strengthen health systems to ensure that they
      are capable of delivering effective interventions and of assessing their
      effectiveness in controlling malaria.

PMID- 17227647
TI  - An update on Chagas disease (human American trypanosomiasis).
AB  - Human American trypanosomiasis or Chagas disease -- named after Carlos Chagas who
      first described it in 1909 -- exists only on the American continent. It is caused
      by a parasite, Trypanosoma cruzi, that is transmitted to humans by blood-sucking
      triatomine bugs, by blood transfusion, and transplacentally. Chagas disease has
      two, successive phases: acute and chronic. The acute phase lasts 6-8 weeks. After
      several years of starting the chronic phase, 20%-35% of infected individuals (the
      percentage varying with geographical area) develop irreversible lesions of the
      autonomous nervous system in the heart, the oesophagus, the colon and/or the
      peripheral nervous system. Data on the prevalence and distribution of Chagas
      disease markedly improved in quality during the 1980s, as a result of
      demographically representative, cross-sectional studies carried out in countries
      where no accurate information on these parameters was available. Experts had
      previously met in Brasilia, in 1979, and devised standard protocols for carrying
      out country-wide studies not only on the prevalence of human infection with T.
      cruzi but also on house infestation with the triatomine vectors. Thanks to a co
      ordinated programme in the southernmost countries of South America (i.e.the
      'Southern Cone'), transmission of T. cruzi by the vectors or blood transfusion
      has been successfully interrupted in Uruguay (from 1997), Chile (from 1999) and
      Brazil (from 2005), and the global incidence of new human infection with T. cruzi
      has decreased by 67%. Similar multi-country control initiatives have been
      launched in the Andean countries and in Central America, with the goal of
      interrupting all transmission of T. cruzi to humans by 2010 -- a goal set, in
      1998, as a resolution of the World Health Assembly. Recent advances in basic
      research on T. cruzi include the genetic characterization of populations of the
      parasite and the sequencing of its genome.

PMID- 17227648
TI  - African trypanosomiasis.
AB  - Trypanosomiasis remains one of the most serious constraints to economic
      development in sub-Saharan Africa and, as a consequence, related research has
      been subject to strong social and political as well as scientific influences. The
      epidemics of sleeping sickness that occurred at the turn of the 20th Century
      focussed research efforts on what became known as 'the colonial disease'. This
      focus is thought to have produced 'vertical' health services aimed at this one
      disease, while neglecting other important health issues. Given the scale of these
      epidemics, and the fact that the disease is fatal if left untreated, it is
      unsurprising that sleeping sickness dominated colonial medicine. Indeed, recent
      evidence indicates that, if anything, the colonial authorities greatly under
      estimated the mortality attributable to sleeping sickness. Differences in
      approach to disease control between Francophone and Anglophone Africa, which in
      the past have been considered ideological, on examination prove to be logical,
      reflecting the underlying epidemiological divergence of East and West Africa.
      These epidemiological differences are ancient in origin, pre-dating the colonial
      period, and continue to the present day. Recent research has produced control
      solutions, for the African trypanosomiases of humans and livestock, that are
      effective, affordable and sustainable by small-holder farmers. Whether these
      simple solutions are allowed to fulfil their promise and become fully integrated
      into agricultural practice remains to be seen. After more than 100 years of
      effort, trypanosomiasis control remains a controversial topic, subject to the
      tides of fashion and politics.

PMID- 17227649
TI  - Echinococcosis: historical landmarks and progress in research and control.
AB  - Although hydatid cysts were recognised and described in ancient times, in both
      livestock and humans, it was not until the 17th Century that their biological
      nature began to be understood. The past 50 years have seen a veritable revolution
      in knowledge and technology applicable to the biology of the cestodes and the
      diseases they cause. The parasites that form hydatid cysts belong to the genus
      Echinococcus, which is now recognized as a complex of closely related cestode
      parasites adapted to a variety of host-assemblages linked by predator-prey
      relationships. Synanthropic transmission in dogs and domestic livestock greatly
      increases the possibilities of zoonotic transmission, and the highest prevalences
      of Echinococcus infection in humans therefore occur in populations engaged in
      livestock rearing in which domestic dogs have access to the viscera of the
      livestock that serve as intermediate hosts. The application of modern scientific
      technology over the last few decades has not only revealed the diversity of host
      parasite relationships within the genus Echinococcus but also led to greatly
      improved technology for the diagnosis and treatment of the echinococcoses in
      humans and lower animals. Although control programmes have led to marked
      reductions in transmission in certain geographical and socio-political settings,
      transmission and the resultant diseases continue unabated throughout most of the
      parasites' world-wide distribution.

PMID- 17227650
TI  - Loiasis.
AB  - Loiasis affects millions of individuals living in the forest and savannah regions
      of Central Africa. In some areas, this disease constitutes one of the most common
      reasons for medical consultation. The burden posed by loiasis is probably under
      estimated and, in addition, individuals harbouring high Loa microfilarial loads
      are at risk of developing serious neurological reactions after treatment with
      diethylcarbamazine or ivermectin. These events are currently significantly
      hampering the development of the African Programme for Onchocerciasis Control,
      and operational research is required to address the issue. The results of recent
      studies, involving either human populations from endemic areas or monkey models,
      have provided much more detail of the mechanisms associated with amicrofilaraemic
      or so-called 'occult' loiasis. New diagnostic tools have also been developed in
      the last decade, and various protocols are now available for the risk-free
      treatment of loiasis cases.

PMID- 17227653
TI  - [Deep venous thrombosis--who, what, why?].

PMID- 17227651
TI  - Towards the elimination of onchocerciasis.
AB  - Human onchocerciasis is a severely disabling filarial disease that is endemic in
      28 African countries, six Latin American countries and Yemen. The disease causes
      a high burden of blindness and visual loss, along with itching and other severe
      dermal manifestations. It constitutes a significant obstacle to socio-economic
      development in highly endemic riverine areas, where the Simulium blackflies that
      act as vectors breed. Onchocerciasis has been subject to control efforts for more
      than 50 years, initially mainly through vector control but since 1988, with free
      access to ivermectin (Mectizan), also through large-scale chemotherapy. The
      Onchocerciasis Control Programme in West Africa operated successfully from 1974
      to 2002 in 11 countries, covering the worst savannah foci of the disease through
      vector control and, in its later stages, also through ivermectin distribution.
      The African Programme for Onchocerciasis Control was established in 1995, to
      cover the remaining endemic areas in Africa, with the sustainable annual
      distribution of ivermectin by 2010 its main goal. Meanwhile, the Onchocerciasis
      Elimination Program for the Americas is making rapid progress in the virtual
      regional elimination of the disease through ivermectin distribution, which is
      achievable primarily because the vectors in the western hemisphere are less
      efficient than those elsewhere. The global elimination of onchocerciasis as a
      public-health problem is now within reach but this will require long-term
      strategies to secure the great gains made so far, through ivermectin treatment
      and local vector control. Research is needed to define the optimal approaches
      with the existing tools and to intensify the development of alternative
      strategies, such as macrofilaricidal drugs for wide-scale use.

PMID- 17227654
TI  - [Deep venous thrombosis--epidemiology, diagnosis and treatment].
AB  - The pathogenesis of deep vein thrombosis (DVT) involves vascular changes or
      injury, stasis and alterations in the blood composition. The risk increases with
      age; however, important risk factors are cancer, surgery, immobilisation and
      hormone therapy. DVT most often appears in the crural veins. The diagnosis is
      based on ultrasound, d-dimer and clinical examination. Correct treatment requires
      gradient compression hosiery, low-molecular heparins and anticoagulant therapy.
      Duration of treatment depends on the individual risk of recurrence.

PMID- 17227655
TI  - [Outpatient treatment of deep-vein thrombosis].
AB  - INTRODUCTION: The treatment of deep-vein thrombosis (DVT) is increasingly managed
      in an outpatient setting. This is the first retrospective study of an outpatient
      treatment program for DVT patients in a Danish hospital. MATERIALS AND METHODS:
      Case records from all DVT patients treated at Frederikshavn Hospital between 1997
      and 2003 were studied to analyse patient characteristics and the risk of
      pulmonary embolism, bleeding and recurrence. Questionnaires about the use of
      outpatient treatment programs were sent to all Danish hospitals. RESULTS: A total
      of 265 patients were registered, of whom 141 (53.2%) were treated in an inpatient
      setting, 120 (45.3%) were treated only in an outpatient setting and 4 (1.5%)
      underwent initial inpatient treatment for less than 24 hours followed by
      outpatient treatment. The percentage of patients in ambulatory care increased
      during the study period. Outpatient treatment proved to be as safe as treatment
      during hospitalisation. Most hospitals reported that the majority of DVT patients
      are still managed in primary hospitalisation. CONCLUSION: The organisation used
      by Frederikshavn is recommended to hospitals that plan to utilise an outpatient
      treatment program for DVT patients. A certain delay must be expected in the
      transition from an inpatient to an outpatient setting. International studies have
      documented the cost-effectiveness as well as patient benefits and preferences
      from such programs.

PMID- 17227656
TI  - [Possible therapeutic intervention with inhibitors and promoters of phospholipase
      A2 subtypes].
AB  - Phospholipase A2 (PLA2) is a group of enzymes discovered more than a century ago
      in insect and snake poison. Not more than 20 years ago they were identified in
      vertebrates, and during the last five years, research has accelerated in relation
      to isolating and cloning several members of this super-family in humans. PLA2
      inhibitors are in the process of being developed for pharmaceutical use. The
      purpose of this review is to outline the relevance and prospectives of PLA2 in a
      clinical perspective.

PMID- 17227658
TI  - [Comparison of registration of data from the Danish Childhood Diabetes Register
      and The National Discharge Register].
AB  - In 1996 The Danish Childhood Diabetes Register (DIA-REG B&U) was established.
      Data are validated yearly against The National Discharge Register (NDR). In the
      first seven years, 1509 cases were found either in the DSBD or in the NDR. Four
      percent did not have diabetes. Two percent had another code than DE10. In 5.2%
      cases, the first registration dates in NDR were a half year or more after onset
      of diabetes. In addition, there were 29 cases only found in the DSBD. In
      conclusion, the sensitivity and specificity is high in the NDR, but there is some
      misclassification and the first admission dates are not equal to the date of
      disease onset. Thus, studies of diabetes in childhood should be based on a
      validated register such as the DIA-REG B&U.

PMID- 17227657
TI  - [Therapy with stem cells for acute ischemic heart disease: myocardial
      regeneration?].
AB  - Treatment of ischemic heart disease with injections of bone-marrow-derived stem
      cells is a promising new modality. However, recent medium-sized placebo
      controlled trials in patients with acute myocardial infarction have not been
      conclusive regarding the treatment effect. This short review aims to elucidate
      some of the unresolved issues raised by the first clinical trials. These include
      long-term safety, tissue-distribution of infused cells, selecting the optimal
      cell type and number, timing of the treatment, and the mechanism of a potential
      treatment effect.

PMID- 17227659
TI  - [Transgastric necrosectomy by open surgery in necrotising acute pancreatitis].
AB  - INTRODUCTION: Conventional surgery for necrotising acute pancreatitis is often
      associated with high mortality and morbidity rates. The aim of this study was to
      describe the initial experience with a new and presumed lesser invasive surgical
      procedure. MATERIAL AND METHODS: The outcome of patients who underwent
      transgastric necrosectomy and subsequent marsupialisation due to necrotising
      pancreatitis was registered. RESULTS: Seven patients (five males, two females)
      with a median age of 47 years (range 32-62 years) had surgery. The reasons for
      pancreatitis were: gallstones (n = 4), idiopathic (n = 2) and alcohol (n = 1).
      The median time from onset of symptoms to surgery was 40 days (range 29-90 days).
      Four patients (57%) had an uneventful post-operative stay. Three patients (43%)
      had one or more complications requiring invasive therapy. Two of these patients
      needed repeated surgery. The median postoperative hospitalisation was 18 days
      (range 10-65 days). There was no post-operative mortality. At a three-month
      follow-up, one patient had exocrine pancreatic insufficiency, and one patient had
      both exocrine pancreatic insufficiency and diabetes mellitus. CONCLUSION:
      Transgastric necrosectomy seems to be associated with a low risk of complications
      for selected patients with necrotising acute pancreatitis. However, further
      experience with the procedure is needed in order to draw valid conclusions.

PMID- 17227660
TI  - [Prostate cancer in Denmark 1943-2002].
AB  - INTRODUCTION: Previous studies in Denmark have reported an increase in prostate
      cancer (PC) incidence- and mortality rates. So far, it has not been possible to
      establish the rising incidence as a consequence of an increase in diagnostic
      procedures. This study reviews the trends in PC incidence and mortality rates in
      Denmark during the 60-year-period from 1943 to 2002. MATERIAL AND METHODS:
      Register-based study. RESULTS: The age-standardised (World Standard Population)
      rate of PC in Denmark increased from 11.4/100,00 in the period 1943-47 to
      38.2/100,000 in the period 1998-2002. Mortality rate increased from 13.5/100,000
      in 1953 to 19.1/100,000 in the period 1993-98. Within the last 10 years changes
      in age-distribution and clinical stage, especially among younger patients,
      indicate a shift towards a more active diagnostic policy. CONCLUSION: In
      concordance with other studies we found an increasing PC incidence. In the last
      10-year-period studied from 1993 to 2002, our study found the rise in incidence
      most likely explained by an increase in diagnostic activity, presumably as
      unsystematic PSA-based "gray-zone screening". This development contrasts with the
      national recommendation for PSA-based screening for PC. The rising incidence will
      necessitate allocation of increased resources for evaluation, treatment, and
      follow-up of patients with PC.

PMID- 17227661
TI  - [Experiences from a stress clinic. A pilot study].
AB  - INTRODUCTION: The aim of the study was to develop a multi-disciplinary stress
      management program for employees with long-term stress. METHODS: In a two-year
      period, 66 people active in the labour market were referred to the stress clinic
      at an occupational medicine clinic. All but 10 went through the program for four
      months and were further evaluated after one year regarding employment, symptoms
      and salivary cortisol. The program consisted of 1) an evaluation of symptoms of
      depression and stress, 2) stress management consultations, 3) introduction to
      relaxation techniques and physical exercise and 4) in some cases contact to the
      work place for adjustments or referral to psychiatric evaluation. Physiological
      measures such as maximal oxygen uptake, blood pressure, cholesterol, HDL, TSH,
      HbA1C, fasting glucose and fibrinogen were carried out at baseline and after four
      months. Salivary cortisol was measured at baseline, after four months and one
      year. As a control group 24 people with similar symptoms referred to the Clinic
      of Occupational Medicine were used. RESULTS: A significantly larger number of
      people in the study group (82%) than in the control group (42%) were employed
      after one year. There was no difference between the two groups regarding the
      prevalence of stress symptoms during the follow-up period, even though the
      prevalence decreased significantly. However, the prevalence of depression was
      significantly lower after one year in the study group (4%) compared to the
      control group (40%). Maximum oxygen uptake increased and fibrinogen decreased
      significantly in four months. The rise in salivary cortisol from awakening until
      30 minutes later increased significantly during one year and correlated with
      symptoms of depression.

PMID- 17227663
TI  - [Severe hyperventilation as a differential diagnosis of acute coronary syndrome].
AB  - We report a case where a 30-year-old, otherwise healthy female was admitted to
      hospital with symptoms of hyperventilation, including chest discomfort and an
      abnormal ECG showing ST depressions and T-wave inversions. The ECG changes
      disappeared spontaneously during the next 24 hours as the patient was calmed
      down. A few weeks after discharge, the ECG changes were partially reproduced
      during a six-minute hyperventilation test. It is worth remembering that severe
      hyperventilation can cause ECG changes similar to those seen in acute coronary
      syndrome.

PMID- 17227662
TI  - [Procalcitonin for early diagnosis of bacteraemia in children with cancer].
AB  - INTRODUCTION: Fever and infections are common complications in children with
      cancer during chemotherapy. The purpose of this study was to investigate the
      usefulness of procalcitonin (PCT) in the identification of children with
      bacteraemia at time of admission with febrile episodes. Furthermore, we compared
      the usefulness of procalcitonin with that of C-reactive protein (CRP). MATERIAL
      AND METHODS: We evaluated 55 febrile episodes in 34 children in treatment for
      cancer. We found 24 episodes of bacteraemia and 31 episodes with negative blood
      cultures. RESULTS: The median PCT and CRP levels in children with positive blood
      cultures were significantly higher compared with children with negative blood
      cultures. The optimum cut-off level to predict bacteraemia was 1 mg/l for PCT and
      50 mg/l for CRP. In distinguishing between febrile episodes with and without
      bacteraemia, PCT was found to have higher positive predictive value and similar
      negative predictive value as compared to CRP at the optimum cut-off level.
      CONCLUSION: These results show the potential usefulness of PCT as an early
      indicator for bacteraemia in febrile children with cancer and furthermore
      indicate that PCT may be more sensitive than CRP in the assessment of the cause
      of fever in these children.

PMID- 17227664
TI  - [Penetrated IUD as the cause of stricture in the sigmoid colon].
AB  - A 42-year-old woman became pregnant for the second and third times following
      insertion of an IUD in the puerperium of her first pregnancy. The IUD was thought
      to have been expelled. Nineteen years after insertion, the woman developed
      abdominal pain and diarrhoea. A sigmoid stricture was diagnosed by endoscopy.
      Laparotomy showed that the IUD had perforated the uterus and penetrated the
      sigmoid colon. Resection was performed. This case demonstrates the need to
      investigate every case of a missing IUD.

PMID- 17227665
TI  - [Acute myocardial infarction during pregnancy].
AB  - Acute myocardial infarction in pregnancy is a rare condition. Two cases of
      suspected acute myocardial infarction during pregnancy are presented. Acute
      myocardial infarction in pregnancy is most often caused by atherosclerosis. Other
      possible aetiologies are dissection, embolism and arterial spasm. Acute coronary
      angiography is recommended as an early diagnostic procedure that does not present
      any risk to the embryo. Treatment with aspirin and heparin is safe, but there
      have been only a few case studies of the use of the newer antithrombotic drugs,
      chlopidogrel and GPIIb-IIIa inhibitors, in pregnant women.

PMID- 17227667
TI  - Relationship between quality of life and child traffic fatalities.
AB  - Traffic injuries are the leading cause of morbidity and mortality of children
      around the world. Economic development and quality of life are main components of
      public health. Using canonical correlation analysis, this study examined the
      relationship between quality of life and traffic fatality among children. Data
      were collected from 19 countries by using World Health Organization and OECD
      statistics. The results indicated that there is a strong relationship between
      quality of life and children traffic fatality. Growing quality of life has become
      protective against child traffic accident mortality. Increasing in gross national
      income per capita, life expectancy at birth number of years, road motor vehicles
      per thousand population, and share of persons of working age (15-64 years) in
      employment also increases children traffic safety.

PMID- 17227666
TI  - New methods to identify and rank high pedestrian crash zones: an illustration.
AB  - Identifying and ranking high pedestrian crash zones plays a key role in
      developing efficient and effective strategies to enhance pedestrian safety. This
      paper presents (1) a Geographical Information Systems (GIS) methodology to study
      the spatial patterns of pedestrian crashes in order to identify high pedestrian
      crash zones, and (2) an evaluation of methods to rank these high pedestrian crash
      zones. The GIS based methodology to identify high pedestrian crash zones includes
      geocoding crash data, creating crash concentration maps, and then identifying
      high pedestrian crash zones. Two methods generally used to create crash
      concentration maps based on density values are the Simple Method and the Kernel
      Method. Ranking methods such as crash frequency, crash density, and crash rate,
      as well as composite methods such as the sum-of-the-ranks and the crash score
      methods are used to rank the selected high pedestrian crash zones. The use of
      this methodology and ranking methods for high pedestrian crash zones are
      illustrated using the Las Vegas metropolitan area as the study area. Crash data
      collected for a 5-year period (1998-2002) were address matched using the street
      name/reference street name intersection location reference system. A crash
      concentration map was then created using the Kernel Method as it facilitates the
      creation of a smooth density surface when compared to the Simple Method. Twenty
      two linear high crash zones and seven circular high crash zones were then
      identified. The GIS based methodology reduced the subjectivity in the analysis
      process. Results obtained from the evaluation of methods to rank high pedestrian
      crash zones show a significant variation in ranking when individual methods were
      considered. However, rankings of high pedestrian crash zones were relatively
      consistent with little to no variation when the sum-of-the-ranks method and the
      crash score method were used. Thus, these composite methods are recommended for
      use in ranking high pedestrian crash zones instead of individual methods.

PMID- 17227669
TI  - Skin reactivity to thimerosal and phenol-preserved Montenegro antigen in Brazil.
AB  - A randomized double-blind trial was performed to determine the frequency of
      positive reactions to the Montenegro antigen (leishmanin) preserved in thimerosal
      (Merthiolate) 1:10,000 or phenol 0.4%. The respective products were tested
      separately in 400 young healthy individuals from a non-endemic area for
      Leishmaniases. Each volunteer received one of the following reagents:
      merthiolated antigen, phenolated antigen, merthiolated saline, or phenolated
      saline. The frequency of positive responses to each reagent after the first
      application was as follows: 0% (phenolated saline), 9.2% (merthiolated saline),
      34.6% (antigen in phenolated saline), and 41.1% (antigen in merthiolated saline).
      After 1 week, volunteers who had tested positive for merthiolated or phenolated
      antigen were retested with the respective preservative, while negatives were
      retested with the preservative they had not received during the first test. In
      all, 331 volunteers who received merthiolated saline during the study, of whom 41
      (12.4%) tested positive. Meanwhile, 326 volunteers who received phenolated
      saline, 4 (1.2%) tested positive. Positive reactions in each group were similar
      in relation to gross appearance skin reactions. Considering the high frequency of
      hypersensitivity to thimerosal in the study population, it is recommended that
      this compound should be replaced as a preservative of the leishmanin antigen.
      Almost 30% of positive reactions to Montenegro antigen in what is considered a
      non-endemic region was surprising and will be the object of future studies.

PMID- 17227668
TI  - Population genetic structure of the malaria vector Anopheles moucheti in south
      Cameroon forest region.
AB  - We used recently developed microsatellite DNA markers to explore the population
      genetic structure of the malaria vector, Anopheles moucheti. Polymorphism at 10
      loci was examined to assess level of genetic differentiation between four A.
      moucheti populations from South Cameroon situated 65-400 km apart. All
      microsatellite loci were highly polymorphic with a number of distinct alleles per
      locus ranging from 9 to 17. Fst estimates ranging from 0.0094 to 0.0275 (P <
      0.001) were recorded. These results suggest a very low level of genetic
      differentiation between A. moucheti populations. The recently available
      microsatellite loci revealed useful markers to assess genetic differentiation
      between geographical populations of A. moucheti in Cameroon.

PMID- 17227670
TI  - New analogs of 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 with
      conformationally restricted side chains: evaluation of biological activity and
      structural determination of VDR-bound conformations.
AB  - We have successfully prepared E- and Z- isomers of 17-20 dehydro analogs of 2
      methylene-19-nor-(20S)-1alpha,25-dihydroxyvitamin D3 (2MD). Both isomers bind to
      the recombinant rat vitamin D receptor (VDR) with high affinity. The Z-isomer
      (Vit-III 17-20Z) displays activity in vivo and in vitro that is similar to 2MD.
      The in vitro activity of the E-isomer (Vit-III 17-20E) is comparable to the
      natural hormone, though in vivo this analog is significantly less calcemic.
      Crystal structures of the rat VDR ligand binding domain complexed with the
      analogs demonstrate that the Vit-III 17-20Z analog is oriented almost identically
      to 2MD, with only minor differences induced by the planar configuration around
      the C17-C20 double bond. The Vit-III 17-20E analog is oriented in a conformation
      distinct from both 2MD and the natural hormone. The structural comparisons
      suggest that the position of C21 in the ligand binding site may be an important
      determinant of biological activity.

PMID- 17227671
TI  - A new EGFR inhibitor induces apoptosis in colon cancer cells.
AB  - The use of agents targeting EGFR represents a new frontier in colon cancer
      therapy. Among these, mAbs and EGFR tyrosine kinase inhibitors seemed to be the
      most promising. However they have demonstrated scarce utility in therapy, the
      former being effective only at toxic doses, the latter resulting inefficient in
      colon cancer. This paper presents studies on a new EGFR inhibitor, FR18, a
      molecule containing the same naphthoquinone core as shikonin, an agent with great
      anti-tumor potential. In HT29, a human colon carcinoma cell line, flow cytometry,
      immunoprecipitation, and Western blot analysis, confocal spectral microscopy have
      demonstrated that FR18 is active at concentrations as low as 10 nM, inhibits EGF
      binding to EGFR while leaving unperturbed the receptor kinase activity. At
      concentration ranging from 30 nM to 5 microM, it activates apoptosis. FR18 seems
      therefore to have possible therapeutic applications in colon cancer.

PMID- 17227672
TI  - Identification of amino acid residues in the Ah receptor involved in ligand
      binding.
AB  - The Ah receptor (AhR) is a ligand-activated transcription factor. Five amino
      acids as candidate amino acids necessary for ligand binding within or near the
      ligand-binding domain were selected based on their evolutional conservation and
      their aromatic nature that could interact with xenobiotic ligands. These amino
      acids were changed to Ala, and the mutated AhRs were subjected to a test of their
      transactivation activity in HeLa cells. Mutation of Phe318 completely lost its
      activity whereas other mutations only weakly impaired activity. The Leu
      substituted mutant, AhR(Phe318Leu), activated the luciferase activity to the
      level comparable to wild type in the cells treated with 3-methylcholanthrene (MC)
      but not at all with beta-naphthoflavone (beta-NF). Ligand-binding activity of
      mutants was examined with [3H]MC in vitro. AhR(Phe318Ala) could not bind to
      [3H]MC. [3H]MC bound by AhR(Phe318Leu) was competed with unlabeled MC but not
      with beta-NF. A structural model of the ligand-binding domain was constructed.

PMID- 17227673
TI  - Shedding off specific lipid constituents from sperm cell membrane during
      cryopreservation.
AB  - Membrane damage is one of the main reasons for reduced motility and fertility of
      sperm cells during cryopreservation. Using a model system of sperm
      cryopreservation developed in our laboratory, we have investigated the detailed
      changes due to cryopreservation in the plasma membrane lipid composition of the
      goat epididymal sperm cells. Total lipid and its components, i.e., neutral
      lipids, glycolipids and phospholipids decreased significantly after
      cryopreservation. Among neutral lipids sterols, steryl esters and 1-O-alkyl-2,3
      diacyl glycerols decreased appreciably, while among phospholipids, major loss was
      observed for phosphatidyl choline and phosphatidyl ethanolamine. Unsaturated
      fatty acids bound to the phospholipids diminished while the percentage of
      saturated acids increased. The cholesterol:phospholipid ratio enhanced and the
      amount of hydrocarbon, which was unusually high, increased further on
      cryopreservation. The data indicates that profound increase of the hydrophobicity
      of the cell membrane is one of the major mechanisms by which spermatozoa acquire
      potential to resist or combat stress factors like cryodamage. The results are
      compatible with the view that for survival against cryodamage, sperm cells
      modulate the structure of their outer membrane by shedding off preferentially
      some hydrophilic lipid constituents of the cell membrane.

PMID- 17227674
TI  - The selective retention of lutein, meso-zeaxanthin and zeaxanthin in the retina
      of chicks fed a xanthophyll-free diet.
AB  - Lutein and zeaxanthin are pigmented oxygenated carotenoids, or xanthophylls,
      derived from plants and concentrated in the retina of primates and birds. We
      investigated the transport, distribution and depletion of lutein and zeaxanthin
      in the plasma and tissues of newly hatched chicks fed xanthophyll-free diets. One
      day-old Leghorn chicks were randomly divided into two groups. A control group was
      fed a diet containing lutein and zeaxanthin (5.2 and 1.7 mg/kg diet,
      respectively) for 28 days. An experimental group was fed a diet containing no
      lutein and zeaxanthin for 28 days. Plasma and tissues were analyzed for lutein
      and zeaxanthin at 28 days (control) and on days 1, 14 and 28 (experimental). At
      hatching, lutein and zeaxanthin were the predominant carotenoids present in the
      blood and tissues. As indicated by their similar mass contents, there was
      complete transfer of these carotenoids from egg yolk to chick. Lutein and
      zeaxanthin concentrations in the plasma and tissues of chicks fed the xanthophyll
      free diet decreased rapidly to almost zero (with a depletion time of seven days
      [t(1/2)]). In contrast, the retina retained its initial concentrations of lutein
      and zeaxanthin similar to the control group. meso-Zeaxanthin and cis-zeaxanthin
      were identified only in the retina. The retina concentrated zeaxanthin over
      lutein. Lutein and zeaxanthin were selectively retained in the retinas of chicks
      fed a xanthophyll-free diet. In contrast, the plasma and other tissues lost up to
      90% of their original content of xanthophylls. These data emphasize the relative
      stability of lutein and zeaxanthin in the cone-rich retina where they are present
      as esters in oil droplets. The tissue depletion suggests the need for a regular
      dietary intake of lutein and zeaxanthin because of rapid depletion in the body.
      It is clear that these xanthophylls may have an essential role in the cone-rich
      retina of the chick as evidenced by their selective retention.

PMID- 17227675
TI  - Characterization of early retinal progenitor microenvironment: presence of
      activities selective for the differentiation of retinal ganglion cells and
      maintenance of progenitors.
AB  - The maintenance and differentiation of retinal progenitors take place in the
      context of the microenvironment in which they reside at a given time during
      retinal histogenesis. To understand the nature of the microenvironment in the
      developing retina, we have examined the influence of activities present during
      the early stage of retinal histogenesis on enriched retinal progenitors, using
      the neurosphere model. Early and late retinal progenitors, enriched as
      neurospheres from embryonic day 14 (E14) and E18 rat retina, respectively, were
      cultured in embryonic day 3 (E3) chick retinal conditioned medium, simulating the
      microenvironment present during early retinal histogenesis. Examination of the
      differentiation and proliferation of retinal progenitors revealed that the early
      microenvironment contains at least three regulatory activities, which are
      partitioned in different size fractions of the conditioned medium with different
      heat sensitivity. First, it is characterized by activities, present in heat
      stable <30 kDa fraction, that promote the differentiation of retinal ganglion
      cells (RGCs), the early born neurons. Second, it contains activities, present in
      heat-sensitive >30 kDa fraction, that regulate the number of early born neurons
      and maintain the pool of retinal progenitors. Third, it possesses activities,
      present in heat-sensitive <30 kDa fraction, that prevent the premature
      differentiation of early retinal progenitors into the late born neurons. Thus,
      our observations demonstrate the regulatory influence of microenvironment on the
      maintenance and differentiation of retinal progenitors and establish neurospheres
      as a viable model system for the examination of such influences.

PMID- 17227676
TI  - Sequential injection affinity chromatography utilizing an albumin immobilized
      monolithic column to study drug-protein interactions.
AB  - In this study, sequential injection affinity chromatography was used for drug
      protein interactions studies. The analytical system used consisted of a
      sequential injection analysis (SIA) manifold directly connected with convective
      interaction media (CIM) monolithic epoxy disks modified by ligand-immobilization
      of protein. A non-steroidal, anti-inflammatory drug, naproxen (NAP) and bovine
      serum albumin (BSA) were selected as model drug and protein, respectively. The
      SIA system was used for sampling, introduction and propulsion of drug towards to
      the monolithic column. Association equilibrium constants, binding capacity at
      various temperatures and thermodynamic parameters (free energy DeltaG, enthalpy
      DeltaH) of the binding reaction of naproxen are calculated by using frontal
      analysis mathematics. The variation of incubation time and its effect in on-line
      binding mode was also studied. The results indicated that naproxen had an
      association equilibrium constant of 2.90 x 10(6)M(-1) at pH 7.4 and 39 degrees C
      for a single binding site. The associated change in enthalpy (DeltaH) was -27.36
      kcal mol(-1) and the change in entropy (DeltaS) was -73 cal mol(-1)K(-1) for a
      single type of binding sites. The location of the binding region was examined by
      competitive binding experiments using a biphosphonate drug, alendronate (ALD), as
      a competitor agent. It was found that the two drugs occupy the same class of
      binding sites on BSA. All measurements were performed with fluorescence
      (lambda(ext)=230 nm, lambda(em)=350 nm) and spectrophotometric detection
      (lambda=280 nm).

PMID- 17227677
TI  - Quantitative determination of organic priority pollutants in the composts of
      sewage sludge with rice straw by gas chromatography coupled with mass
      spectrometry.
AB  - In order to investigate the occurrence and distribution of organic contaminants
      in the compost of sewage sludge with rice straw, four different composting
      treatments at a low carbon/nitrogen (C/N) ratio (13:1) were conducted. Thirty
      semi-volatile organic compounds (SVOCs) listed as priority pollutants by both
      China and the US Environmental Protection Agency (EPA) were Soxhlet-extracted,
      separated and analyzed by gas chromatography coupled with mass spectrometry (GC
      MS). The results showed that after composting (56 days) most of SVOCs were
      detected in the final composts. The total concentrations of polycyclic aromatic
      hydrocarbons (PAHs) and phthalic acid esters ranged from 1.8 to 10 mg/kg dry
      weight (d.w.) and from 9.8 to 18 mg/kg d.w., respectively, being significantly
      higher than those of chlorobenzenes and nitroaromatic compounds which were
      generally less than 1.0 mg/kg d.w. The concentrations and predominant compounds
      of organic contaminants in the different composts varied, and were affected by
      their physico-chemical properties and the composting processes. Concentrations of
      SVOCs in the static aerated composting processes especially intermittently
      aerated composting treatment were considerably lower than those in the manual
      turned composting treatments. Concentrations of organic contaminants especially
      PAHs and di(2-ethylhexyl) phthalate in the final composts were in agreement with
      the maximum permissible limits for agricultural purposes proposed by the European
      Union and by the EPA.

PMID- 17227678
TI  - Cognitive fatigue of executive processes: interaction between interference
      resolution tasks.
AB  - A resource depletion framework motivated a novel strategy for investigating
      whether the central executive is unitary or separable into relatively independent
      subprocesses. The idea that tasks with overlapping neural representations may
      involve similar executive components was also critical to our approach. Of
      particular interest were tasks requiring resolution of interference among
      competing representations. Within a single experimental session intensive
      training reduced the ability to resolve interference on a transfer task if the
      training task placed high demands on interference resolution. Negative transfer
      was absent when interference resolution was minimally required by the task, or
      when the training and transfer tasks did not rely on overlapping neural
      representations. These results suggest a nonunitary central executive composed of
      separable subcomponents, at least one of which mediates interference resolution.
      Our results are consistent with an executive control process specialized for the
      selection of task-relevant representations from competitors. The results also
      agree with the view that higher cognitive processes are resource limited and can
      be temporarily depleted.

PMID- 17227680
TI  - The first case of mitoxantrone exposure in early pregnancy.
AB  - Mitoxantrone is an antineoplastic agent considered a potential human teratogen
      because of its mechanism of action and is classified by the US Food and Drug
      Administration in pregnancy category risk D. In the literature there are only
      four cases of women exposed to the drug in late pregnancy. We report the first
      case of mitoxantrone therapy in the first trimester and during the pregnancy. A
      41-year-old woman affected with multiple sclerosis, conceived during therapy and
      continued mitoxantrone until 29 weeks and 3 days of her pregnancy. She delivered
      by cesarean section at 39 weeks a growth restricted female baby weighing 1950g
      without evidence of congenital malformations.

PMID- 17227679
TI  - Do deep dyslexia, dysphasia and dysgraphia share a common phonological
      impairment?
AB  - This study directly compared four patients who, to varying degrees, showed the
      characteristics of deep dyslexia, dysphasia and/or dysgraphia--i.e., they made
      semantic errors in oral reading, repetition and/or spelling to dictation. The
      "primary systems" hypothesis proposes that these different conditions result from
      severe impairment to a common phonological system, rather than damage to task
      specific mechanisms (i.e. grapheme-phoneme conversion). By this view, deep
      dyslexic/dysphasic patients should show overlapping deficits but previous studies
      have not directly compared them. All four patients in the current study showed
      poor phonological production across different tasks, including repetition,
      reading aloud and spoken picture naming, in line with the primary systems
      hypothesis. They also showed severe deficits in tasks that required the
      manipulation of phonology, such as phoneme addition and deletion. Some of the
      characteristics of the deep syndromes - namely lexicality and imageability
      effects - were typically observed in all of the tasks, regardless of whether
      semantic errors occurred or not, suggesting that the patients' phonological
      deficits impacted on repetition, reading aloud and spelling to dictation in
      similar ways. Differences between the syndromes were accounted for by variation
      in other primary systems--particularly auditory processing. Deep dysphasic
      symptoms occurred when the impact of phonological input on spoken output was
      disrupted or reduced, either as a result of auditory/phonological impairment, or
      for patients with good phonological input analysis, when repetition was delayed.
      'Deep' disorders of reading aloud, repetition and spelling can therefore be
      explained in terms of damage to interacting primary systems such as phonology,
      semantics and vision, with phonology playing a critical role.

PMID- 17227681
TI  - Inactivation and purification of cowpea mosaic virus-like particles displaying
      peptide antigens from Bacillus anthracis.
AB  - Chimeric cowpea mosaic virus (CPMV) particles displaying foreign peptide antigens
      on the particle surface are suitable for development of peptide-based vaccines.
      However, commonly used PEG precipitation-based purification methods are not
      sufficient for production of high quality vaccine candidates because they do not
      allow for separation of chimeric particles from cleaved contaminating species.
      Moreover, the purified particles remain infectious to plants. To advance the CPMV
      technology further, it is necessary to develop efficient and scalable
      purification strategies and preferably eliminate the infectivity of chimeric
      viruses. CPMV was engineered to display a 25 amino acid peptide derived from the
      Bacillus anthracis protective antigen on the surface loop of the large coat
      protein subunit. The engineered virus was propagated in cowpea plants and
      assembled into chimeric virus particles displaying 60 copies of the peptide on
      the surface. An effective inactivation method was developed to produce non
      infectious chimeric CPMV virus-like particles (VLPs). Uncleaved VLPs were
      separated from the contaminating cleaved forms by anion exchange chromatography.
      The yield of purified chimeric VLPs was 0.3 g kg(-1) of leaf tissue. The results
      demonstrate the ability to generate multi-gram quantities of non-infectious,
      chimeric CPMV VLPs in plants for use in the development of peptide-based
      vaccines.

PMID- 17227683
TI  - Dissimilarities in the vocal control over communication and echolocation calls in
      bats.
AB  - Bats, like other mammals, use communication calls for social interaction, but
      rely at the same time on sophisticated echolocation systems for orientation and
      prey capture. Both call types are of laryngeal origin, but can be distinguished
      on the basis of their spectral and temporal features and apparently their
      functional involvement as well. Although they share a common final motor pathway,
      there is evidence that separate vocally active brainstem areas are involved in
      the functional control of communication and echolocation calls. This review
      summarizes findings that support the above assumption, and focus on the
      functional involvement of the periaqueductal gray, the paralemniscal area, and
      the nucleus of the brachium of the inferior colliculus, in differentiated vocal
      control.

PMID- 17227682
TI  - Sensory neuron-specific receptor agonist BAM8-22 inhibits the development and
      expression of tolerance to morphine in rats.
AB  - We observed that intrathecal (i.t.) bovine adrenal medulla 22, an endogenous
      opioid peptide, partially reverses morphine tolerance. However, its mechanism
      remains unclear. The present study determined the effects of BAM8-22, a
      derivative of BAM22 and selective sensory neuron-specific receptor (SNSR)
      agonist, on the development and maintenance of tolerance to spinal morphine.
      Intrathecal administration of BAM8-22 at various doses (0.1, 1 and 10nmol) did
      not alter withdraw latencies assessed in both paw withdraw and tail flick tests.
      Co-administration of BAM8-22 (0.1nmol) every other day, but not daily, with
      morphine remarkably attenuated the development of morphine tolerance.
      Pretreatment and co-treatment with BAM8-22 (0.1nmol) significantly reversed
      established morphine tolerance. Furthermore, intermittent administration of BAM8
      22 with morphine consistently resumed morphine-induced antinociception. However,
      i.t. BAM8-22 did not alter morphine-induced hyperalgesia. These results suggested
      that SNSR may be able to modulate the sensitivity of opioid receptor serving as a
      most probable underlying mechanism for the effects of BAM8-22 on morphine
      tolerance. This study also demonstrated that intermittent combination of SNSR
      agonist BAM8-22 with morphine might be better regimen for long-term use of
      opioids to treat chronic pain.

PMID- 17227684
TI  - Impaired social interaction and reduced anxiety-related behavior in vasopressin
      V1a receptor knockout mice.
AB  - The arginine vasopressin (AVP) system plays an important role in social behavior.
      Autism, with its hallmark disturbances in social behavior, has been associated
      with the V1a receptor (V1aR) gene. Furthermore, impairments of social function
      are often observed in symptoms of schizophrenia. Subchronic phencyclidine (PCP)
      produces behaviors relating to certain aspects of schizophrenic symptoms such as
      impairing social interaction in animals and it reduces the density of V1aR
      binding sites in several brain regions. Here, we report that V1aR knockout (KO)
      mice exhibited impairment of social behavior in a social interaction test, and
      showed reduced anxiety-related behavior in elevated plus-maze and marble-burying
      behavior tests. Given the current findings, the V1aR may be involved in the
      regulation of social interaction, and V1aR KO mice could be used as an animal
      model of psychiatric disorders associated with social behavior deficits, such as
      autism and schizophrenia.

PMID- 17227685
TI  - The transcriptional regulatory network of the amino acid producer Corynebacterium
      glutamicum.
AB  - The complete nucleotide sequence of the Corynebacterium glutamicum ATCC 13032
      genome was previously determined and allowed the reliable prediction of 3002
      protein-coding genes within this genome. Using computational methods, we have
      defined 158 genes, which form the minimal repertoire for proteins that presumably
      act as transcriptional regulators of gene expression. Most of these regulatory
      proteins have a direct role as DNA-binding transcriptional regulator, while
      others either have less well-defined functions in transcriptional regulation or
      even more general functions, such as the sigma factors. Recent advances in genome
      wide transcriptional profiling of C. glutamicum generated a huge amount of data
      on regulation of gene expression. To understand transcriptional regulation of
      gene expression from the perspective of systems biology, rather than from the
      analysis of an individual regulatory protein, we compiled the current knowledge
      on the defined DNA-binding transcriptional regulators and their physiological
      role in modulating transcription in response to environmental signals. This
      comprehensive data collection provides a solid basis for database-guided
      reconstructions of the gene regulatory network of C. glutamicum, currently
      comprising 56 transcriptional regulators that exert 411 regulatory interactions
      to control gene expression. A graphical reconstruction revealed first insights
      into the functional modularity, the hierarchical architecture and the topological
      design principles of the transcriptional regulatory network of C. glutamicum.

PMID- 17227686
TI  - A theoretical study of phenolic compounds with antioxidant properties.
AB  - Quantum chemical calculations at the DFT/B3LYP, HF, and AM1 and PM3 semiempirical
      levels were employed to calculate a set of molecular properties for 41 phenol
      compounds with antioxidant activity. The significant molecular descriptors
      related to the compounds were the vertical ionization potentials (IPvs) and the
      charge on oxygen atom 7. The IPv has been calculated using Koopman's theorem IPv=
      epsilon(HOMO(DFT)), IPv=-epsilon(HOMO(HF)) and as the difference of energy
      calculations for the corresponding cation and for the neutral form IPv(E(cation)
      E(neutral)) obtained with the DFT/B3LYP method. The best model obtained showed
      not only the statistical significance but also predictive ability.

PMID- 17227687
TI  - Induction of secretory immunity and memory at mucosal surfaces.
AB  - Mucosal epithelia comprise an extensive vulnerable barrier which is reinforced by
      numerous innate defence mechanisms cooperating intimately with adaptive immunity.
      Local generation of secretory IgA (SIgA) constitutes the largest humoral immune
      system of the body. Secretory antibodies function both by performing antigen
      exclusion at mucosal surfaces and by virus and endotoxin neutralization within
      epithelial cells without causing tissue damage. SIgA is thus persistently
      containing commensal bacteria outside the epithelial barrier but can also target
      invasion of pathogens and penetration of harmful antigens. Resistance to toxin
      producing bacteria such as Vibrio cholerae and enterotoxigenic Escherichia coli
      appears to depend largely on SIgA, and so does herd protection against horizontal
      faecal-oral spread of enteric pathogens under naive or immunized conditions--with
      a substantial innate impact both on cross-reactivity and memory. Like natural
      infections, live mucosal vaccines or adequate combinations of non-replicating
      vaccines and mucosal adjuvants, give rise not only to SIgA antibodies but also to
      longstanding serum IgG and IgA responses. However, there is considerably
      disparity with regard to migration of memory/effector cells from mucosal
      inductive sites to secretory effector sites and systemic immune organs. Also,
      although immunological memory is generated after mucosal priming, this may be
      masked by a self-limiting response protecting the inductive lymphoid tissue in
      the gut. The intranasal route of vaccine application targeting nasopharynx
      associated lymphoid tissue may be more advantageous for certain infections, but
      only if successful stimulation is achieved without the use of toxic adjuvants
      that might reach the central nervous system. The degree of protection obtained
      after mucosal vaccination ranges from reduction of symptoms to complete
      inhibition of re-infection. In this scenario, it is often difficult to determine
      the relative importance of SIgA versus serum antibodies, but infection models in
      knockout mice strongly support the notion that SIgA exerts a decisive role in
      protection and cross-protection against a variety of infectious agents.
      Nevertheless, relatively few mucosal vaccines have been approved for human use,
      and more basic work is needed in vaccine and adjuvant design, including
      particulate or live-vectored combinations.

PMID- 17227688
TI  - Safety and tolerability of a high-potency zoster vaccine in adults >/= 50 or
      years of age.
AB  - BACKGROUND: Herpes zoster (HZ) incidence rises with age, especially after 50
      years of age, probably due to waning varicella-zoster virus (VZV)-specific
      immunity. The Shingles Prevention Study [Oxman MN, Levin MJ, Johnson GR, Schmader
      KE, Straus SE, Gelb LD, et al. A vaccine to prevent herpes zoster and
      postherpetic neuralgia in older adults, N Engl J Med 2005;352:2271-84], enrolled
      people >/= 60 or years of age and showed that zoster vaccine prevents HZ and
      postherpetic neuralgia (PHN), presumably through boosting VZV-specific immunity.
      This study of people >/= 50 or years of age compared the safety and tolerability
      of two zoster vaccine potencies. METHODS: Adults >/= 50 or years old enrolled in
      a randomized, double-blind, multicenter study to compare the safety and
      tolerability of one dose of two zoster vaccine potencies, approximately 58,000
      and approximately 207,000 plaque-forming units/dose. Adverse experiences (AEs)
      were recorded on a standardized Vaccination Report Card for 42 days
      postvaccination. For assessment of injection-site AEs, clinically acceptable
      tolerability was predefined based on experience with PNEUMOVAX 23, a licensed
      vaccine recommended for use in older people. RESULTS: Six hundred and ninety
      eight subjects (age 50-90 years, median 64 years) were enrolled. No serious
      vaccine-related AEs were reported. Similar AE rates were observed in the higher
      and lower potency groups (overall systemic AEs: 37.5 and 39.3%, vaccine-related
      systemic AEs: 10.9 and 13.2%, injection-site AEs: 63.0 and 59.8%). Rates for a
      combined endpoint of moderate or severe injection-site pain/tenderness/soreness
      and swelling were 17.2% (95% CI 13.9, 21.0) and 9.0% (95% CI 5.6, 13.4),
      respectively. Most combined endpoint events were reported as moderate in
      intensity. CONCLUSIONS: Both vaccine potencies were generally well tolerated in
      this study of people > or years of age. Although rates of some moderate or severe
      injection-site AEs were greater in the higher potency group, all rates met the
      prespecified criteria for clinically acceptable tolerability.

PMID- 17227689
TI  - Utility of the aged BALB/c mouse model to demonstrate prevention and control
      strategies for severe acute respiratory syndrome coronavirus (SARS-CoV).
AB  - The causative agent of Severe Acute Respiratory Syndrome (SARS) was identified as
      a coronavirus (CoV) following the outbreak of 2002-2003. There are currently no
      licensed vaccines or treatments for SARS-CoV infections. Potential prevention and
      control strategies that show promise in vitro must be evaluated in animal models.
      The aged BALB/c mouse model for SARS supports a high level of viral replication
      in association with clinical illness and disease that mimics SARS in the elderly.
      We tested two preventive strategies, vaccination and passive transfer of serum
      antibody, to determine the extent of protection achieved against SARS-CoV
      challenge in this model. These approaches were able to achieve or induce antibody
      titers sufficient to reduce viral load, protect from weight loss and reduce or
      eliminate histopathologic changes in the lungs of aged mice. This study validates
      the utility of the aged BALB/c mouse model for evaluation of the efficacy of
      vaccines and immunoprophylaxis.

PMID- 17227690
TI  - Development and registration of recombinant veterinary vaccines. The example of
      the canarypox vector platform.
AB  - The canarypox vaccine vector (ALVAC) technology has been used to develop and
      license several vaccines for companion animals and horses in the European Union
      and USA. ALVAC is a ubiquitous vector with high biosafety since it is non
      replicative in mammalians, is genetically and physically stable, and able to
      induce both humoral and cell-mediated immune responses against the expressed
      transgene product. Specific rules apply for the development and registration of
      recombinant vector vaccines. The biology of the vector as well as the recombinant
      virus must be thoroughly documented to allow the risk assessment of its use in
      the target species. In particular, its safety for the host and the environment
      must be extensively demonstrated before field trials can be authorized.

PMID- 17227691
TI  - European Pharmacopoeia foot-and-mouth disease vaccine potency testing in cattle:
      between test variability and its consequences.
AB  - In the event of a foot-and-mouth (FMD) outbreak in a densely populated livestock
      area within the European Community, emergency vaccination will most likely be
      employed. The objective of the present study was to support the European FMD
      control policy by evaluating the between test variability of the European
      accepted method for assessing the potency, a major determinant in vaccine choice,
      of an FMD vaccine batch. The test system suffers from low in vivo repeatability
      and reproducibility (67.6 and 58.8%, respectively). Consequently, the results of
      10 identical, individual vaccine potency tests using an FMD virus O1 Manisa
      vaccine batch indicate that the obtained potency of a vaccine with an overall 50%
      protective dose (PD(50)) value of 9.99 may vary from 4.59 to 24.25 PD(50).

PMID- 17227692
TI  - Water balances in intensively monitored forest ecosystems in Europe.
AB  - A soil hydrological model based on Darcy's law was used to calculate hydrological
      fluxes for 245 intensively monitored forest plots in Europe. Local measured input
      data for the model were rather limited and input was partly based on generic
      data. To obtain the best results, the model was calibrated on measured
      throughfall at the plots. Median transpiration fluxes are 350 mm; median leaching
      fluxes are 150 mm yr(-1) with the highest values in areas with high rainfall.
      Uncertainty analyses indicate that the use of local meteorological data instead
      of generic data leads to lower leaching fluxes at 70% of the plots due to an
      overestimation of the wind speed on basis of main meteorological stations. The
      underestimation of the leaching fluxes is confirmed by the median Cl fluxes which
      were slightly positive for the considered plots.

PMID- 17227693
TI  - Effect of fluoride intoxication on endometrial apoptosis and lipid peroxidation
      in rats: role of vitamins E and C.
AB  - Fluoride is a strong, hard anion and cumulative toxic agent. The effect of
      fluoride intoxication on lipid peroxidation in endometrial tissue and the
      protective effects of combinations of vitamins E and C in rats were studied.
      Additionally, the apoptotic changes in endometrial tissue were examined.
      Experimental groups were as follows: control group; a group treated with 100 mg/l
      fluoride (F group); and a group treated with 100 mg/l fluoride plus vitamins E
      and C (F+Vit group). The F and F+Vit groups were treated orally with fluoride for
      30 days. Vitamins E and C were injected simultaneously at doses of 50 mg/kg day
      i.m. and 20 mg/kg day body weight i.p. Extensive formation of DNA strand breaks,
      the typical biochemical feature of apoptosis, was detected with the use of the
      terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick and
      labeling (TUNEL) method. Malondialdehyde (MDA) levels were determined in uterine
      tissue of rats. Fluoride caused a significant increase in MDA levels (an
      important marker of lipid peroxidation) in the fluoride group compared with the
      controls (p<0.05). Vitamins E and C significantly reduced the fluoride-induced
      lipid peroxidation in the F+Vit group compared with the F group (p<0.05). Diffuse
      apoptosis in glandular epithelium and stromal cells was found in endometrial
      tissues of F treated rats by TUNEL method. The severity of these lesions was
      reduced by the administration of vitamins. From these results, it can be
      concluded that subchronic fluoride administration causes endometrial apoptosis,
      and lipid peroxidation may be a molecular mechanism involved in fluoride-induced
      toxicity. Furthermore, treatment with a combination of vitamins E and C reduced
      endometrial apoptosis caused by fluoride.

PMID- 17227694
TI  - Elevated cerebrospinal fluid F2-isoprostane levels indicating oxidative stress in
      healthy siblings of multiple sclerosis patients.
AB  - Lipid peroxidation has been implicated in the pathogenesis of multiple sclerosis
      (MS). Isoprostanes, isomers of prostaglandins, are produced by free radical
      mediated peroxidation of fatty acids in vivo and can be quantified in biological
      fluids. This study examines the levels of cerebrospinal fluid (CSF) F2
      isoprostanes (F2-iPs) in MS patients (n=46), their healthy siblings (n=46) and
      unrelated controls (n=50). The median CSF F2-iP concentration (range) was
      significantly higher in siblings of MS patients, as compared to healthy controls
      (40.0 [7.1-68.7] and 29.1 [6.4-60.3] pg/mL, respectively, p=0.031). MS patients
      demonstrated F2-iP levels intermediate between siblings and controls. F2-iP
      levels in MS patients and siblings correlated significantly (R=0.360, p=0.012).
      These results suggest that siblings of MS patients have an increased oxidative
      stress response to environmental and/or genetic factors that may be involved in
      MS pathogenesis.

PMID- 17227695
TI  - Simultaneous reconstruction of upper and lower lip beside chin and nasal lobule:
      in a case of facial chemical burn.

PMID- 17227696
TI  - Tissue expansion in burn sequelae repair.
AB  - Burns may cause emotional, aesthetic and functional sequelae. Extended or
      hypertrophic scars are usually difficult to repair using local tissues, and the
      use of skin grafts may cause further injuries to the donor sites. The use of
      tissue expanders may offer a better option in the treatment of burn sequelae.
      This is a report on our experience using tissue expanders in 54 cases (23
      patients) of burn sequelae located in different anatomical areas. Fourteen of the
      patients were female and nine male ranging in age between 5 and 48. The expanders
      were placed in the subgaleal, submuscular, subfascial or subcutaneous planes.
      Skin expansion was completed in 50 cases (92.5%). The injured area was removed by
      advancement flaps in 44 cases and by transposition flaps in 6 of them. Primary
      expansion was performed in 42 cases and reexpansion in 12. The rate of
      complications was 24.07%, of which 30.8% were considered to be absolute and 69.2%
      relative. Tissue expansion is an excellent option for burn sequelae treatment
      because it provides skin of similar local characteristics and does not damage the
      donor site. The procedure can be repeated in the event of major sequelae
      (reexpansion).

PMID- 17227697
TI  - Personality disorders in early adolescence and the development of later substance
      use disorders in the general population.
AB  - Assessments of personality disorder (PD) and conduct disorder (CD) in a random
      community sample at mean age 13 were employed to predict subsequent substance
      abuse disorder (SUD), trajectories of symptoms of abuse or dependence on alcohol,
      marijuana, or other illicit substances, and hazard of initiating marijuana use
      over the subsequent decade. Personality disorders and conduct disorder were
      associated with diagnoses and symptoms of SUDs in every model and their effects
      were independent of correlated family risks, participant sex, and other Axis I
      disorders. Specific elevated PD symptoms in early adolescence were also
      associated with differential trajectories of already initiated SUD symptoms as
      well as elevated risk for future onset of SUD symptoms. For several models the
      greatest of these effects were shown for borderline PD and for conduct disorder,
      the predecessor of adult antisocial PD. Passive-aggressive PD also showed
      independent elevation effects on substance use symptoms for alcohol and
      marijuana. Analyses over 30 years suggest that Cluster B PD (borderline,
      histrionic, narcissistic) are independent risks for development of SUD and
      warrant clinical attention.

PMID- 17227699
TI  - Endometrial safety after 5 years of continuous combined transdermal estrogen and
      intrauterine levonorgestrel delivery for postmenopausal hormone substitution.
AB  - OBJECTIVE: To investigate endometrial histology and thickness of the endometrium
      after long-term use of continuous transdermal estrogen substitution combined with
      intrauterine release of levonorgestrel (LNG) in postmenopausal women. DESIGN: A 5
      year non-comparative prospective clinical trial. SUBJECTS: Out of 182 symptomatic
      postmenopausal women using estrogen substitution therapy (EST) combined with a
      novel T-shaped LNG-releasing intrauterine system (Femilis Slim LNG-IUS), to
      prevent endometrial proliferation and bleeding, only those women (n=102) who used
      two consecutive LNG-IUSs, were isolated with the aim to study the long-term
      effects on the endometrium. The mean age of the women was 57 years (range 47-71).
      The majority of women received percutaneous 17beta estradiol, 1.5mg daily, or an
      equivalent dose by patch or orally, on a continuous basis. MAIN OUTCOME MEASURES:
      Endometrial histology and ultrasonographic evidence of endometrial suppression,
      after a period of approximately 5 years of use. The mean duration of use of the
      regimen was 70 months (range 25-98). RESULTS: The dominant endometrial histologic
      picture was that of inactive endometrium characterized by glandular atrophy and
      stroma decidualization (Kurman classification 5b). No cases of endometrial
      hyperplasia were found. On transvaginal ultrasound, this corresponds with a thin
      endometrium (< or = 5 mm). CONCLUSION: The results of this 5-year study in 102
      postmenopausal women using EST demonstrates that the LNG-IUS effectively opposes
      the estrogenic effect on the endometrium resulting in strong suppression during
      the entire period of EST. Due to its high efficacy and absence of systemic
      effects on organ tissues (e.g., breasts), target delivery in the uterine cavity
      could be a preferred route to administer a progestagen in women using EST.

PMID- 17227698
TI  - Childhood sexual abuse and the course of alcohol dependence development: findings
      from a female twin sample.
AB  - Childhood sexual abuse (CSA) has been associated with increased risk for alcohol
      dependence (AD), but the extent to which CSA history may impact transitions in
      the course of AD development remains unclear. The current study examined the role
      of CSA in initiation of alcohol use and rate of progression from first drink to
      AD using a sample of 3536 female twins (mean age=21.6 years). Psychiatric
      diagnoses and alcohol use histories were obtained via telephone interviews using
      an adaptation of the SSAGA. The contribution of CSA to alcohol outcomes
      independent of familial influences was estimated by using co-twin AD status to
      adjust for familial liability to AD. CSA was associated with higher rates of both
      lifetime alcohol use and AD, but CSA-associated risk for consumption of first
      alcoholic drink was evident only at ages 12 and 13. Rate of transition from first
      alcohol use to AD did not differ by CSA status. Findings indicate that CSA and
      elevated risk for AD may be linked via early age at first drink and that
      progression from first drink to AD follows a similar course among women with and
      without histories of CSA.

PMID- 17227700
TI  - Antibacterial activity and in vitro anti-tumor activity of the extract of the
      larvae of the housefly (Musca domestica).
AB  - One of the significant characteristics of traditional Chinese medicine is the use
      of insects, other terrestrial arthropods and their products as drugs. In the
      present work, the extract of housefly (Musca domestica) larvae was studied by an
      agar well diffusion assay and minimum bactericidal concentration (MBC)
      determination for detection of antimicrobial activity and by MTT assay method to
      test its in vitro anti-tumor activity. In our studies, the extract inhibited six
      tested bacterial pathogens and Escherichia coli Jm109, a gene-modified strain
      resistant to ampicillin with the MBCs ranging from 200 to 1600 microg/ml, while
      Gram-positive bacteria were more sensitive than Gram-negative bacteria. The
      extract showed high in vitro anti-tumor activity against human colon cancer cell
      line CT26 with the IRs ranging from 62 to 89%. The extract of housefly larvae
      inoculated with Shigella dysenteriae 51302 exhibited higher antibacterial
      activity and in vitro anti-tumor activity than that of native larvae, which may
      indicate the same principle involved in the use of Bombyx mori larvae infected
      with silk moth fungus Beauveria bassiana and Hepialis larvae infected with
      Cordiceps fungus in the traditional Chinese medicine. Both extracts did not show
      any coagulation activity and haemolysis activity against rabbit erythrocytes at
      500 and 1000 microg/ml. The results support its use in the traditional Chinese
      medicine, and warrant the further identification of the active molecule in the
      housefly larvae.

PMID- 17227703
TI  - High prevalence of SHV-12 and the emergence of CTX-M-12 in clinical isolates of
      Klebsiella pneumoniae from Korea.

PMID- 17227702
TI  - Inactivation of ppk differentially affects virulence and disrupts ATP homeostasis
      in Salmonella enterica serovars Typhimurium and Gallinarum.
AB  - Polyphosphate is involved in resistance to stress in a number of bacterial
      species; however, its role in the virulence of Salmonella enterica serovars which
      differ in their host range has not been described. We examined the role of
      polyphosphate kinase in infection, growth and survival of S. Typhimurium (broad
      host range) and S. Gallinarum (avian-adapted). We also used ppk mutants to assess
      the downstream effects on intracellular ATP levels. ppk mutants had significantly
      (P<0.05) elevated ATP in stationary phase compared to the wild-type and,
      depending on the serovar, were defective in growth, survival and virulence. The
      virulence of S. Typhimurium ppk::SpcStr was significantly (P<0.05) attenuated
      following oral infection of both Rhode Island Red chickens and BALB/c mice. In
      contrast, inactivation of the ppk gene of S. Gallinarum did not affect growth or
      virulence. The differential contribution of polyphosphate to the virulence of S.
      Typhimurium and S. Gallinarum may reflect aspects of the pathogenesis and host
      range of these serovars. The ppk mutant of both serovars survived significantly
      less well (P<0.05) in a saline starvation-survival model, relative to the
      respective parent. The effect of ppk mutation on survival was formally described
      by fitting the data to the Weibull model and by estimation of k(max). Measurement
      of rpoS promoter activity using a lacZ transcriptional fusion demonstrated
      repression of rpoS in a ppk background, confirming a role for polyphosphate in
      RpoS induction. Together the data indicate the crucial importance of maintaining
      stable intracellular ATP during infection and nutritional stress. We suggest that
      polyphosphate plays a central role in homeostasis during growth and stress.

PMID- 17227704
TI  - Social disability in different mental disorders.
AB  - OBJECTIVE: To assess the social disability of people with different psychiatric
      disorders. METHODS: Cross-site survey in five psychiatric hospitals (Dresden,
      Wroclaw, London, Michalovce and Prague). Working-aged patients diagnosed (ICD-10)
      with schizophrenia and related disorders (F2), affective disorders (F3), anxiety
      disorders (F4), eating disorders (F5) and personality disorders (F6), were
      assessed at admission (n=969) and 3 months after discharge (n=753) using the
      Brief Psychiatric Rating Scale and the Groningen Social Disability Schedule. The
      main outcome measure was Interviewer-rated social disability. RESULTS: During
      acute episodes patients with personality, eating and schizophrenic disorders
      functioned less effectively than those with affective or anxiety disorders. After
      controlling for age and severity of psychopathology, there was no significant
      effect of the diagnosis (during remission), sex, education and history of
      disorder on disability. Site, employment and partnership were significant factors
      for the level of social disability in both measure points. CONCLUSION: Severity
      of psychopathological symptoms, not the diagnosis of a mental disorder, was the
      most significant factor in determining the level of social functioning,
      particularly during the remission period. Site, employment and partnership
      appeared as significant factors influencing the level of social disability.

PMID- 17227705
TI  - Cavum septum pellucidum in patients with first episode psychosis and individuals
      at high risk of psychosis.

PMID- 17227706
TI  - Psychopathological consequences after a terrorist attack: an epidemiological
      study among victims, the general population, and police officers.
AB  - BACKGROUND AND AIM: To assess the prevalence and correlates of post-traumatic
      stress disorder (PTSD), major depression and anxiety disorders other than PTSD,
      among three samples with different level of exposure to the March 11, 2004
      terrorist attacks in Madrid. METHOD: We sampled three groups of persons-those
      injured in the attacks, the residents of Alcala de Henares, and police officers
      involved with the rescue effort-with different exposure to the March 11, 2004
      terrorist attacks, using random sampling from comprehensive censuses of all three
      groups. In person interviews were conducted with all three groups between 5 and
      12 weeks after March 11, 2004. Questionnaire included assessment of socio
      demographic characteristics, of PTSD using the Davidson trauma scale, and of a
      range of psychiatric illnesses using the mini international neuropsychiatric
      interview (MINI). RESULTS: The overall sample included 127 persons injured in the
      attack, 485 residents of Alcala de Henares, and 153 policemen involved in rescue.
      Of all three groups 57.5%, 25.9% and 3.9% of persons, respectively, reported
      symptoms consistent with any assessed psychiatric disorder. The use of
      psychoactive medication before March 11, 2004 was consistently the main predictor
      of PTSD and major depression among those injured and of major depression and
      anxiety disorders others than PTSD among residents of Alcala. CONCLUSIONS: There
      was a substantial burden of psychological consequences of the March 11, 2004
      terrorist attacks two months after the event. Persons with prior mental illness
      are at higher risk of post-event psychopathology, across groups of exposure.

PMID- 17227707
TI  - Computerized assessment of cognition in schizophrenia: promises and pitfalls of
      CANTAB.
AB  - OBJECTIVE: Over the last decade, the Cambridge Neuropsychological Test Automated
      Battery (CANTAB), which comprises visuo-spatial tasks, has been utilized in
      cognitive studies of schizophrenia. A clear approach concerning the usage of
      CANTAB for the appraisal of neurocognitive dysfunction in schizophrenia is
      currently lacking. METHOD: In this paper, we have first reviewed the overall
      applications of CANTAB and then evaluated methodological strengths and weaknesses
      of CANTAB as a neurocognitive battery for schizophrenia. We carried out a
      systematic search and assessment of studies where CANTAB was utilized to measure
      cognitive function in schizophrenia. We have also attempted to quantify the
      available data and perform a meta-analysis, but this approach turned out to be
      still premature. RESULTS: CANTAB has enabled researchers to highlight significant
      deficits affecting broad cognitive domains in schizophrenia, such as working
      memory, decision-making, attention, executive functions and visual memory. So
      far, the most consistent deficit observed with CANTAB testing has been
      attentional set-shifting, suggestive of fronto-striatal dysfunctions. In
      addition, preliminary evidence points towards the potential use of CANTAB to
      identify cognitive predictors of psychosocial functioning, to describe the
      relationships between symptoms and cognition, and to measure the impact of
      pharmacological agents on cognitive functioning. CONCLUSION: CANTAB has been used
      successfully to highlight the range of visuo-spatial cognitive deficits in
      schizophrenia, producing similar results to those obtained with some traditional
      neuropsychological tests. Further studies validating the use of CANTAB following
      the standard set by Measurement And Treatment Research to Improve Cognition in
      Schizophrenia (MATRICS) are warranted.

PMID- 17227708
TI  - The role of Shp2 (PTPN11) in cancer.
AB  - Tyrosyl phosphorylation, which is controlled by protein-tyrosine kinases (PTKs)
      and protein-tyrosine phosphatases (PTPs), regulates numerous cellular processes.
      Altered expression and/or mutations in PTKs are linked to many forms of cancer,
      yet until recently little was known about the roles of PTPs in normal cells or in
      cancer. Earlier work established that a member of the PTP superfamily, PTEN, is
      an important tumor suppressor gene. We now know that at least one other PTP, the
      SH2 domain-containing phosphatase Shp2, is a bona fide oncogene that is mutated
      in several types of leukemia and hyperactivated by other mechanisms in some solid
      tumors. Understanding how Shp2 and other PTPs contribute to oncogenesis should
      provide new insights into pathogenesis and might suggest new targets for anti
      neoplastic drugs.

PMID- 17227709
TI  - The 25-hydroxyvitamin D threshold for better health.
AB  - Available data supporting a target serum level of at least 75 nmol/l 25
      hydroxyvitamin D (25-OHD) include studies on bone mineral density (bmd), fracture
      prevention, lower extremity function, and cancer prevention. Given the high cost
      and disability from falls, fractures, and cancer treatment a shared threshold for
      25-OHD has significant public health implications, especially so, if a large part
      of the population is below this threshold. This article summarizes available
      evidence supporting the 75 nmol/l threshold, reviews adherence to Vitamin D
      treatment in fracture trials in regard to achieved anti-fracture efficacy, and
      finally discusses current recommendations for Vitamin D intake.

PMID- 17227710
TI  - Substituted thiophene-anthranilamides as potent inhibitors of human factor Xa.
AB  - A series of thiophene-containing non-amidine factor Xa inhibitors is described.
      Simple methyl-substituted thiophene analogs were relatively weak inhibitors.
      However, introduction of hydrophilic substituents at C-4 or C-5 of the thiophene
      afforded inhibitors with low nanomolar potency. Optimization of the thiophene
      substituent at C-4 afforded subnanomolar inhibitors with improved in vitro
      anticoagulant activity. Incorporating basic amine substituents on the thiophene
      increased hydrophilicity and improved anticoagulant activity. The pharmacokinetic
      profile of one inhibitor was evaluated in dogs, and the X-ray crystal structure
      of this compound bound to factor Xa provides insight into the observed SAR for
      binding to factor Xa.

PMID- 17227712
TI  - Investigations on the effect of high surface albedo on erythemally effective UV
      irradiance: results of a campaign at the Salar de Uyuni, Bolivia.
AB  - Measurements and model calculations have been performed to study the effect of
      high surface albedo on erythemally effective UV irradiance. A central part of the
      investigation has been a one week measurement campaign at Salar de Uyuni in the
      Southern part of the Bolivian Altiplano. The Salar de Uyuni, the largest salt
      lake of the world, is characterized by largely homogeneous surface conditions
      during most of the year. Albedo measurements performed by an UV radiometer result
      in a reflectivity for erythemally effective radiation of 0.69+/-0.02. The
      measurements show hardly any dependency on solar elevation, indicating the
      homogeneity of the surface and nearly isotropic reflection properties of the
      Salar. The effects of the high albedo surface on the erythemally effective
      irradiance, i.e. the UV index (UVI), has been experimentally determined by
      simultaneous measurements of several UV radiometers located at different sites
      around and on the Salar. In this context a method for the minimization of
      systematic deviations between the individual detectors used for the investigation
      is presented. It ensures the intercomparability of the performed UV measurements
      within +/-2% which is a distinct improvement compared to the typical absolute
      accuracy of UV irradiance measurements in the order of +/-5%. For solar
      elevations around 50 degrees the UVI measured close to the center of the Salar is
      typically enhanced by 20% compared to the values determined outside. Towards
      lower solar elevations this increase becomes slightly weaker. The measurements
      agree well with both, own corresponding 1D and previously published 3D radiative
      transfer calculations from literature.

PMID- 17227711
TI  - Development of selective inhibitors for anti-apoptotic Bcl-2 proteins from BHI-1.
AB  - A series of inhibitors for anti-apoptotic Bcl-2 proteins based on BHI-1 were
      synthesized and their binding interactions with Bcl-2, Bcl-X(L), and Bcl-w were
      evaluated. It was found that modification of BHI-1 resulted in varied binding
      profiles among Bcl-2, Bcl-X(L), and Bcl-w, and a set of inhibitors with varied
      selectivity to Bcl-2, Bcl-X(L), and Bcl-w proteins have been identified.
      Molecular modeling of the interaction of the BHI-1 based analogues with the anti
      apoptotic Bcl-2 proteins suggested that the binding site for the BHI-1 based
      inhibitor was the least conserved section among Bcl-2, Bcl-X(L), and Bcl-w:
      targeting the non-conserved section may account for the observed selectivity of
      the BHI-1 based inhibitors among the anti-apoptotic Bcl-2 proteins. The validity
      of the model was supported by a strong correlation between the model-calculated
      binding energy and the experimental binding affinity. In summary, our studies
      suggest that most of the reported inhibitors for anti-apoptotic Bcl-2 proteins
      are nonselective and BHI-1 is a promising template to distinguish among Bcl-2,
      Bcl-X(L), and Bcl-w by targeting the non-conserved domain among the anti
      apoptotic Bcl-2 proteins. Molecular-modeling-aided rational development of BHI-1
      based selective inhibitor for anti-apoptotic Bcl-2 proteins is underway.

PMID- 17227713
TI  - EPR study of copper(II) complexes of hydroxysalen derivatives in order to be used
      in the DNA cleavage.
AB  - Two series of functionalized hydroxy-salen-copper(II) complexes with various side
      chain lengths have been synthesized. The first one is characterised by amino side
      chain protected by the tert-butyloxycarbonyl group (Boc) whereas, the second
      series is obtained by removal of the Boc-protecting group under acidic conditions
      and formation instead of it an ammonium salt. EPR studies were carried out on the
      copper(II) complexes. EPR signals attributed to monomers and dimers of Cu2+
      species were evidenced. Determination of the copper(II) environment in each
      complex was attempted using all the experimental results. Square planar and
      tetrahedral symmetries were found for the copper(II) monomers. From the fine
      structure observed for the pair signal, the distance between the Cu2+ ions in the
      pair has been calculated (3.9-4.3A). From these values, it seems that the
      formation of pairs is obtained by a face-to-face bimolecular association.

PMID- 17227714
TI  - Cross-immunity and antibody responses to different immobilisation serotypes of
      Ichthyophthirius multifiliis.
AB  - Vaccination of channel catfish with either of two serotypes of the parasitic
      ciliate Ichthyophthirius multifiliis conferred protection against challenge
      infection by either serotype. Fish were vaccinated by intracoelomic injection
      with live theronts of isolate G5 (serotype D) or isolate G12 (a new serotype),
      which express different surface immobilisation antigens. Vaccination with live
      G12 theronts conferred complete protection against subsequent challenge by both
      serotypes while vaccination with G5 theronts elicited only partial protection
      against both serotypes. Vaccination with trophont lysates did not protect against
      challenge infection. Sera from vaccinated fish were tested in immobilisation
      assays, ELISAs, and Western blots. Serum antibodies recognised only
      immobilisation antigens of the serotype used for vaccination in immobilisation
      assays or on Western blots. No antigens common to both serotypes were identified
      by Western blots. In contrast, serum antibodies bound antigens in cell lysates
      from both serotypes by ELISA, demonstrating that antibodies recognising both
      serotypes are produced in response to infection, which presumably confer observed
      cross-serotype protection.

PMID- 17227715
TI  - An implantable carotid sinus baroreflex activating system: surgical technique and
      short-term outcome from a multi-center feasibility trial for the treatment of
      resistant hypertension.
AB  - OBJECTIVES: To assess perioperative outcomes and blood pressure (BP) responses to
      an implantable carotid sinus baroreflex activating system being investigated for
      the treatment of resistant hypertension. METHODS: We report on the first
      seventeen patients enrolled in a multicenter study. Bilateral perivascular
      carotid sinus electrodes (CSL) and a pulse generator (IPG) are permanently
      implanted. Optimal placement of the CSL is determined by intraoperative BP
      responses to test activations. Acute BP responses were tested postoperatively and
      during the first four months of follow-up. RESULTS: Prior to implant, BP was
      189.6+/-27.5/110.7+/-15.3 mmHg despite stable therapy (5.2+/-1.8 antihypertensive
      drugs). The mean procedure time was 202+/-43 minutes. No perioperative strokes or
      deaths occurred. System tests performed 1 or up to 3 days postoperatively
      resulted in significant (all p < or = 0.0001) mean maximum reduction, with
      standard deviations and 95% confidence limits for systolic BP, diastolic BP and
      heart rate of 28+/-22 (17, 39) mmHg, 16+/-11 (10, 22) mmHg and 8+/-4 (6, 11) BPM,
      respectively. Repeated testing during 3 months of therapeutic electrical
      activation demonstrated a durable response. CONCLUSIONS: These preliminary data
      suggest an acceptable safety of the procedure with a low rate of adverse events
      and support further clinical development of baroreflex activation as a new
      concept to treat resistant hypertension.

PMID- 17227716
TI  - Initial experience in endovenous laser ablation (EVLA) of varicose veins due to
      small saphenous vein reflux.
AB  - OBJECTIVE: Conventional surgery for varicose veins due to small saphenous reflux
      is associated with high recurrence rates (up to 50%), many resulting from
      inadequate surgery. This prospective audit examines the safety and efficacy of
      EVLA in the treatment of this. METHOD: 65 patients (68 limbs) with varicosities
      due to primary or recurrent sapheno-popliteal junction (SPJ) and small saphenous
      vein (SSV) reflux underwent out-patient EVLA (810 nm diode laser). The SSV was
      ablated from mid-calf to the SPJ. Symptomatic improvement (Aberdeen Varicose Vein
      Severity Score [AVVSS]), time to return to normal activity, post-EVLA analgesic
      requirements, and complications were recorded. RESULTS: Duplex ultrasound follow
      up (median 6-months) confirmed abolition of SPJ/SSV reflux in all limbs following
      a median total laser energy delivery of 1131J (IQR 928-1364) at an energy density
      of 66.3 Joules/cm (IQR 54.2-71.6). AVVSS improved from 15.4 (IQR 11.8-19.7) to
      4.6 (IQR 3.2-6.7) at three months (p<0.001). Median analgesia requirement was 3
      days (23% [15/65] patients required none) and the median time to normal activity
      was 0 (0-4) days (65% [42/65] returning to normal daily activity immediately).
      There were no instances of skin burns or DVT but 3 patients (4.4%) developed
      transient cutaneous numbness (sural nerve). 98% (64/65) patients would undergo
      EVLT again. CONCLUSIONS: EVLA abolished SPJ/SSV reflux in all limbs. This is
      likely to be more effective than conventional surgery, although long-term follow
      up is required. Data from a randomised control trial would be desirable.

PMID- 17227717
TI  - Influence of secondary infection on amputation in chronic critical limb ischemia.
AB  - OBJECTIVES: To evaluate the influence of secondary infection on major amputation
      in chronic critical leg ischemia (CLI). DESIGN: Prospective, controlled
      observational study. MATERIALS AND METHODS: Sixty-seven patients with CLI and
      ischemic lesions participated in the study. Presence of infection was defined by
      clinical, laboratory and radiological criteria. Patients were categorized as
      having no local infection, soft tissue infection or osteomyelitis treated without
      antibiotics, amoxicillin/clavulanacid for 1 month or ciprofloxacin and
      clindamycin for 3 months, respectively. Clinical outcome was assessed at 2, 6 and
      12 months. Study endpoints were major amputation and mortality. Analyses were
      performed using the Kaplan-Meier method. RESULTS: Forty-seven of 67 patients had
      a local infection. Major amputation was lower in patients with successful
      revascularization as compared to patients unsuitable for or with failed (without)
      revascularization (0% vs 26%, p<0.01). In patients with successful
      revascularization the probability of complete healing was lower with secondary
      infection (23% vs 71%, p=0.03). In patients without revascularization complete
      healing was rare (<10%), but secondary infection did not influenced major
      amputation, mortality or serious adverse events. CONCLUSION: Secondary infection
      reduces the likelihood of successful healing following revascularisation of CLI.

PMID- 17227719
TI  - Molecular motions in HIV-1 gp120 mutants reveal their preferences for different
      conformations.
AB  - Both the crystal structures of the HIV-1 gp120 core bound by the CD4 and antigen
      17b, and the SIV gp120 core pre-bound by CD4 are known. We built the homology
      models of gp120 with loops V3 and V4 in the CD4-complex, CD4-free and CD4
      unliganded states, and models of the 375 S/W and 423 I/P mutants in the CD4-free
      and unliganded states, respectively. CONCOORD was utilized for generating
      ensembles of the seven gp120 models that were analyzed by essential dynamics
      analyses to identify their preferred concerted motions. The revealed large-scale
      concerted motions are related to either the receptor association/release or the
      conformational transition between different conformational states. Essential
      subspace overlap analyses were performed to quantitatively distinguish the
      preference for conformational transitions between states of the gp120 mutants and
      further to ascertain what kind of conformational state that the mutants prefer to
      adopt. Results indicate that the 375 S/W mutant, in which the tryptophan indole
      group is predicted to occupy the phe43 pocket in the gp120 interior, favors a
      conformation close to the CD4-bound state. However, the other mutant 423 I/P
      inclines to prevent the formation of bridging sheet and stabilize the
      conformation in the unliganded state. Our theoretical analyses are in agreement
      with experimentally determined mutation effects, and can be extended to a new
      approach to design or screen mutants that have effects on conformation/function
      of a protein.

PMID- 17227720
TI  - Very small injected samples to study chloroquine and quinine in human serum using
      capillary-LC and native fluorescence.
AB  - A comparison between HPLC with conventional fluorescence detection and capillary
      LC (microHPLC) with native laser-induced fluorescence (LIF) detection was done to
      determine chloroquine (CQ) and quinine (Q) in human serum. HPLC experiments were
      run with parameters of the conventional fluorimeter set at the highest level of
      sensitivity. Results were compared with those obtained on microHPLC coupled to a
      ZETALIF (He-Cd 325 nm) detector which provided a 50-fold increase in sensitivity.
      In microHPLC-LIF injection volumes were 200 nL instead of 10 microL in
      conventional HPLC. The separation was completed within 3 min (6 min on HPLC). The
      limit of detection on microHPLC-LIF was 1.9 and 1.3 fmol for CQ and Q,
      respectively. Both experiments were validated on serum samples. The mean recovery
      was more than 95% for CQ and Q. The intra- and inter-day precision and accuracy
      were found to be within the acceptable limits (<10%).

PMID- 17227718
TI  - Nitric oxide differentially regulates the gene expression of caspase genes but
      not some autophagic genes.
AB  - Nitric oxide (NO) is fundamentally important molecule which produces a wide range
      of cellular effects with the most poorly understood one being alteration in the
      sensitivity to cell death. The objective of this study was to test the hypothesis
      that NO would differentially affect caspase or autophagy gene expression in a
      manner that might account for the disparate actions of NO to either enhance or
      protect against cell death. Neonatal mouse cardiomyocytes in culture were treated
      with the NO donor SIN-1 (3-morpholinosydnonimine hydrochloride) for up to 20 h.
      RNA was collected, after either 2, 4 or 20 h, labeled and hybridized to cDNA
      microarray slides The concentration of SIN-1 was selected after concentration
      response studies of SIN-1 on cell viability, assessed by the MTT assay. The cDNA
      microarrays were used that contained the mouse genome version 2.0 with genes for
      enzymes crucial to apoptosis, namely caspases-1, -2, -3, -6, -7, -8, -9, -11, -12
      and -14, as well as for enzymes crucial to autophagy namely beclin-1, Apg5l and
      Apg12l. Considering the entire 20 h period, treatment with SIN-1 was associated
      with significant (p<0.05) changes in five caspases. In contrast, there were no
      changes in the three separate genes involved in autophagy. Time course
      experiments showed a consistent increase in caspase-8, -11 and -14, and a
      consistent decrease in caspase-1 and -6. Notably, caspase-1 showed a persistent
      and marked reduction so that after 20 h of treatment, caspase-1 was dramatically
      reduced, almost ten fold, to 0.14+/-0.11 of control. In conclusion, these results
      suggest that: (i) NO regulates the expression of genes involved in apoptotic but
      not some involved in autophagic cell death; (ii) the more recently discovered
      caspase-14 may have a role in the heart; (iii) NO-induced alteration of different
      caspases may explain the ability of NO to either enhance or protect against cell
      death depending on whether associated factors involve, respectively caspases-8, 
      11, and -14 or -1 and -6.

PMID- 17227721
TI  - Rapid online-SPE-MS/MS method for ketoprofen determination in dermal interstitial
      fluid samples from rats obtained by microdialysis or open-flow microperfusion.
AB  - Pharmacokinetic studies of topical ketoprofen formulations using continuous
      sampling techniques such as microdialysis (MD) or open-flow microperfusion (OFM)
      require sensitive assays due to small sample volumes. A simple and easy online
      SPE-MS/MS method for ketoprofen analysis was developed for both MD and OFM
      samples obtained from rat dermal tissue. The quantification range is 25-5000
      ng/ml with a limit of detection of 3 ng/ml using only 10 microl sample volume.
      The method is characterized by a simple setup using a short polymeric SPE column
      (OASIS HLB) for desalting with 1.5 min run times in combination with a sensitive
      MS detection in negative ESI MRM mode. An easy sample workup procedure was used
      which enables high throughput analysis of a large number of samples for
      pharmacokinetic studies. In addition, a commercial available (fenoprofen) as well
      as an isotopically labelled (deuterated ketoprofen) standard were investigated as
      potential internal standards. The method was validated according to FDA
      guidelines for bioanalytical validation in terms of accuracy, intra-batch and
      inter-batch precision, linearity, matrix effect, recovery and stability for both
      internal standards. Accuracies were 98-113% (fenoprofen) and 95-108% (deuterated
      ketoprofen), intra-batch precision was 2-3% R.S.D. (fenoprofen) and 2-6% R.S.D.
      (deuterated ketoprofen), and inter-batch precision was 2-6% R.S.D. (fenoprofen)
      and 3-6% R.S.D. (deuterated ketoprofen) over the entire quantification range. The
      presented method was applied to dermal interstitial fluid samples obtained in a
      topical administration study of ketoprofen in rats.

PMID- 17227723
TI  - Diarrheal diseases in the history of public health.
AB  - While the public health threat of HIV/AIDS in developing countries has drawn
      increasing attention from the international community for more than two decades,
      other health problems such as diarrheal diseases continue to contribute to higher
      morbidity and mortality rates in much of the developing world. This literature
      review is an account of both the history and current risks associated with
      diarrheal diseases.

PMID- 17227724
TI  - Cystine inhibits creatine kinase activity in pig retina.
AB  - BACKGROUND: Cystinosis is an autosomal recessive disorder associated with
      lysosomal cystine accumulation caused by defective cystine efflux. Visual deficit
      is a possible consequence of cystine accumulation in cornea and retina.
      Fibroblasts from cystinotic patients present ATP deficit with intact
      mitochondrial energy-generating capacity by an unknown mechanism. Considering
      that creatine kinase is a thiol enzyme crucial for energy homeostasis in retina,
      and disulfides like cystine may alter thiol enzymes, the main objective of the
      present study was to investigate the effect of cystine and cysteamine, the drug
      used for treatment of cystinotic patients, on creatine kinase activity in
      cytosolic and mitochondrial fractions of the retina from adult pigs. METHODS:
      Retina was isolated from 6-month-old Landrace pigs, homogenized and mitochondrial
      and cytosolic fractions separated by centrifugation. Cytosolic and mitochondrial
      creatine kinase activities were determined in the presence of different
      concentrations of cystine and/or cysteamine. RESULTS: Cystine inhibited the
      enzyme activity in a dose- and time-dependent manner and cysteamine prevented and
      reversed the inhibition caused by cystine, suggesting that cystine inhibits
      creatine kinase activity by oxidation of the sulfhydryl groups of the enzyme.
      CONCLUSIONS: Considering that creatine kinase is a crucial enzyme for retina
      energy homeostasis, in case cystine leaves lysosome these results provide a
      possible mechanism for cystine toxicity and also another beneficial effect for
      the use of cysteamine in patients with cystinosis.

PMID- 17227725
TI  - Influence of ovariectomy in the right ventricular contractility in heart failure
      rats.
AB  - BACKGROUND: Clinical studies in postmenopausal women suggest that female hormones
      play an important role in maintaining healthy cardiovascular conditions. The
      objective of this study was to evaluate the influence of ovarian hormones in the
      right ventricle contractility in heart failure (HF) rats following myocardial
      infarction (MI). METHODS: Female Wistar rats were divided into four groups:
      healthy ovariectomized (OVX), ovariectomized with HF (OVX-HF), HF, and sham
      operated (SHAM). Ovariectomy was performed in 10-week-old rats, and MI was
      induced 1 week later. Eight weeks after MI, right ventricular (RV) performance
      was analyzed using RV strip preparations. RESULTS: Ovariectomy did not change the
      infarct size (HF: 42 +/- 3.5 vs. OVX-HF: 39 +/- 1.5%). In the presence of
      isoproterenol (ISO) and calcium, the isometric force was reduced in both HF
      groups. Ovariectomy did not modify the positive inotropic parameter in the
      control and in HF rats. Time to peak tension (TPT) was prolonged in both
      ovariectomized groups compared to SHAM (ISO 10(-7) M OVX: 125 +/- 12( *); SHAM:
      81 +/- 4; HF: 87 +/- 4; OVX-HF: 102 +/- 6( *) msec, ( *)p <0.01 vs. SHAM), and
      relaxation time (RT) was prolonged in OVX (270 +/- 16( *) msec) and OVX-HF (241
      +/- 10( *) msec) vs. SHAM (197 +/- 6 msec; ( *)p <0.01 vs. SHAM). CONCLUSIONS: We
      conclude that the absence of female ovarian hormones during nine weeks does not
      influence the right ventricle positive inotropic response, but it prolongs the
      time of contraction and relaxation in normal and in HF rats following MI.

PMID- 17227726
TI  - RCE1 corneal epithelial cell line: its variability on phenotype expression and
      differential response to growth factors.
AB  - BACKGROUND: By serial transfer of rabbit corneal epithelial cells, the
      spontaneous RCE1 cell line was previously established. These cells mimic the
      stage-dependent differentiation of the corresponding cell type. METHODS: RCE1
      cells were cultured either on plastic culture dishes or on collagen rafts to
      compare the epithelial ultrastructure after growth on these substrata. Phenotypic
      variability was studied after subcloning of cells. The differentiation ability of
      each subclone was determined by Western blot with antibodies against the
      differentiation-linked keratin pair K3/K12 and by measuring LDH activity and LDH
      isozymes in cytosolic extracts. The proliferative response of RCE1 cells to EGF,
      TGFalpha, amphiregulin, bFGF or IL-6 was determined under serum-free culture
      conditions. RESULTS: Cells grown on collagen rafts formed 5- to 7-layered
      epithelia with characteristics closer to those found in normal corneal epithelium
      than cells cultivated on plastic substrata, which formed 3- to 5-layered
      epithelia. Subcloning experiments demonstrated that every proliferative cell is
      able to grow and constitute stratified epithelia expressing K3/K12 keratins. LDH
      levels in RCE1 epithelia were similar to those of cultured or freshly harvested
      corneal epithelia; however, they showed a slightly altered LDH isozyme set, with
      prevalence of LDH-3 isoform. Whereas EGF and TGF-alpha were equipotent,
      amphiregulin elicited a 4-fold lower proliferative response. Also, bFGF was 10
      fold less mitogenic than EGF, and IL-6 had the lowest effect with an ED(50) 20
      fold lower than EGF. CONCLUSIONS: The results demonstrate that every RCE1
      proliferative cell has the ability to generate epithelial sheets. We conclude
      that EGF and TGF-alpha are the major effectors of RCE1 cell proliferation.

PMID- 17227727
TI  - Radioiodine treatment in autoimmune hyperthyroidism: analysis of outcomes in
      relation to dosage.
AB  - BACKGROUND: Controversy exists regarding the optimal dose of radioiodine ((131)I)
      therapy in autoimmune hyperthyroidism (i.e., Graves' Disease). METHODS: In order
      to evaluate the efficacy and safety of high dose (131)I therapy in autoimmune
      hyperthyroidism, a retrospective review of patients who received (131)I therapy
      for Graves' disease from 1980 to 2000 in the Instituto Nacional de Ciencias
      Medicas y Nutricion Salvador Zubiran, Mexico City was carried out. RESULTS: The
      study population consisted of 596 autoimmune hyperthyroid patients with a mean
      age of 35 years. The mean follow-up period was 10.31 +/- 2.37 years. Remission of
      hyperthyroidism occurred in 81.9%, persistent hyperthyroidism was recorded in
      14.4% and recurrence in 3.7%. (131)I doses of 5-9 mCi (185-333 MBq) and > or =20
      mCi (> or =740 MBq) were associated with remission rates of 65.5% and 87.7%
      respectively. Remission occurred earlier and more often with high doses of
      (131)I. The high-dose group (20-30 mCi [740-1110 MBq]) had the lowest rate of
      persistence (9.7, 27.5 and 34.3%, for 20-30 [740-1110 MBq], 10-14 [370-518 MBq]
      and 5-9 [185-333 MBq] mCi, respectively p <0.05) and hypothyroidism occurred
      earlier in this group (p = 0.05). CONCLUSIONS: Remission of autoimmune
      hyperthyroidism is more likely with doses of 20-30 mCi (740-1110 MBq).

PMID- 17227728
TI  - Cytokine production from peripheral blood mononuclear cells in patients with
      ankylosing spondylitis and their first-degree relatives.
AB  - BACKGROUND: To understand the cytokine levels in different disease activities of
      patients with ankylosing spondylitis (AS), we measured proinflammatory and
      antiinflammatory cytokine production from peripheral blood mononuclear cells
      (PBMC) in patients with AS and their first-degree relatives (FDR). METHODS: PBMC
      were obtained from 26 patients with AS and 24 FDR and then stimulated with PHA
      for 72 h. In the supernatants, the following three cytokines, tumor necrosis
      factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-10, were measured
      by ELISA. Disease activity in AS patients was divided into high disease activity
      (Group 1) and low disease activity (Group 2), based on the Bath AS Disease
      Activity Index (BASDAI > or =4 or <4). Healthy FDR of AS patients (Group 3) and
      healthy subjects (Group 4) were used as a control group. RESULTS: TNF-alpha
      production from PBMC was significantly increased in Group 1 patients compared to
      Group 2 patients (1371 +/- 1008 pg/mL vs. 355 +/- 89 pg/mL, p <0.05) or FDR (1371
      +/- 1008 pg/mL vs. 552 +/- 89 pg/mL, p <0.05) or healthy subjects (1371 +/- 1008
      pg/mL vs. 436 +/- 114 pg/mL, p <0.01). IL-1beta also showed a similarly
      significant difference between the two groups (Group 1 vs. Group 2, Group 1 vs.
      Group 4) (p <0.05). In contrast, IL-10 was significantly decreased in Group 1
      when compared to Group 2 (126 +/- 64 pg/mL vs. 272 +/- 150 pg/mL, p <0.05).
      CONCLUSIONS: Patients with high BASDAI had increased production of TNF-alpha and
      IL-1beta compared to those with low BASDAI or healthy FDR, suggesting that
      proinflammatory cytokines may play an important role during active inflammation.

PMID- 17227729
TI  - Effects of calcitonin, risedronate, and raloxifene on erythrocyte antioxidant
      enzyme activity, lipid peroxidation, and nitric oxide in postmenopausal
      osteoporosis.
AB  - BACKGROUND: The aims of this study were to compare erythrocyte antioxidant enzyme
      activities, lipid peroxidation, and nitric oxide levels (NO) in women with
      postmenopausal osteoporosis (PMO) and non-porotic postmenopausal healthy controls
      and to assess the relationship between bone mineral density and these
      oxidant/antioxidant parameters. Additionally, in vivo effects of three different
      anti-osteoporotic drugs, calcitonin, risedronate and raloxifene, on the
      erythrocyte oxidant-antioxidant status in women with PMO were also assessed.
      METHODS: Postmenopausal women aged 40-65 years and without previous diagnosis or
      treatment for osteoporosis and independent in activities of daily living were
      included. Bone mineral density was measured at the lumbar spine and proximal
      femur using DXA. Erythrocyte enzyme activities of superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), catalase (CAT), and lipid peroxidation end
      product malondialdehyde (MDA) and nitrite/nitrate levels, by product of NO, were
      assessed. Fifty-nine women with PMO were included (mean age 56.7 years), 44
      completed course of therapy and were analyzed. Twenty-two non-porotic healthy
      women (mean age 55.8 years) were included as controls. RESULTS: Patients had
      significantly lower CAT and GSH-Px enzyme activity and higher levels of MDA and
      NO than non-porotic healthy controls. Proximal femur BMD measurements
      significantly correlated with NO levels. QUALEFFO scores improved in different
      levels with these short-term treatments. In all treatment groups, erythrocyte MDA
      levels significantly decreased; moreover, risedronate reduced NO levels and
      raloxifene enhanced CAT enzyme activity. CONCLUSIONS: Oxidative stress plays an
      important role in the pathogenesis of PMO. Studied drugs had ultimate effects on
      reducing lipid peroxidation. Raloxifene also had potent effects in the
      enhancement of antioxidant defense system.

PMID- 17227730
TI  - Effect of psychological stress on salivary interleukin-1beta in psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory skin disease in which several Th1
      cytokines such as interleukin-1 beta (IL-beta) have been shown to play a pivotal
      role. Psychological stress has also been implicated in triggering or exacerbating
      the disease. METHODS: Salivary IL-1beta and cortisol levels of 25 patients with
      psoriasis were compared with those of 50 age- and sex-matched healthy controls
      under basal conditions and after a standardized stressful procedure including
      mental arithmetics and the Stroop Color-Word Naming Test. RESULTS: At baseline,
      mean IL-1beta levels were higher in patients with psoriasis than controls (p
      <0.001), whereas mean cortisol levels did not differ significantly between
      groups. Although IL-1beta levels increased after stress among controls, they did
      not increase among patients with psoriasis, with a significant group-by-time
      interaction (p <0.01). After stress, cortisol levels were significantly increased
      in both groups as compared with baseline (p < or =0.001), without any group-by
      time interaction. Perceived stress was similar among psoriatic patients and
      controls. There was no significant correlation between changes in IL-1beta and
      changes in cortisol. CONCLUSIONS: The higher basal IL-1beta levels among
      psoriatic patients suggest that its production is increased. Changes in
      proinflammatory cytokine activity in psoriatic skin may play an important role in
      propagating inflammation. The blunted response of IL-1beta to stress observed in
      psoriatic patients may reflect a "ceiling effect", or be ascribed to a defective
      response of the immune system to adrenergic stimuli.

PMID- 17227731
TI  - Homocysteine concentrations and molecular analysis in patients with congenital
      heart defects.
AB  - BACKGROUND: Congenital heart defects are the result of incomplete heart
      development and, like many diseases, have been associated with high homocysteine
      concentration. METHODS: We evaluated homocysteine, folic acid and vitamin B(12)
      concentrations, and the mutations 677C>T and 1298A>C in MTHFR, 844ins68 in CBS
      and 2756A>G in MTR genes in 58 patients with congenital heart defects, 38 control
      subjects, and mothers of 49 patients and 26 controls. RESULTS: Control and
      patients presented normal range concentrations for homocysteine (7.66 +/- 3.16
      microM and 6.95 +/- 3.12 microM, respectively), folic acid (8.31 +/- 3.00 ng/mL
      and 11.84 +/- 10.74 ng/mL) and vitamin B(12,) (613.56 +/- 307.57 pg/mL and 623.37
      +/- 303.12 pg/mL), which did not differ among groups. For the mothers studied,
      homocysteine and vitamin B(12) concentrations also did not differ between groups.
      However, folic acid concentrations of mothers showed significant difference, the
      highest values being in the group of patients. No difference was found in allele
      frequencies among all groups studied. CONCLUSIONS: In the studied groups, high
      homocysteine seems not to be correlated with congenital heart defects, as well as
      folic acid and vitamin B(12). The mutations studied, in isolation, were not
      related to congenital heart defects, but high concentration of maternal
      homocysteine is associated with the presence of three or four mutated alleles.

PMID- 17227732
TI  - Analysis of the sodium iodide symporter expression in histological slides from a
      nodular goiter.
AB  - BACKGROUND: The aim of the study was analysis at both the level and the cell site
      of the sodium/iodide symporter (NIS) in histological slides from hot, warm, and
      cold nodules and extranodular parenchyma according to scintigraphy. METHODS: The
      study population consisted of 97 people who underwent surgery for a toxic nodular
      goiter (26 patients) or a non-toxic nodular goiter (71 patients).
      Immunohistochemical study was performed with 198 histological slides from hot,
      warm, and cold nodules (study slides) and the extranodular parenchyma (control
      slides). The level of NIS expression was estimated objectively using the
      computerized image analysis system, Quantimet 600S (Leica, Cambridge, UK).
      RESULTS: We found significantly higher NIS expression in hot nodules than in cold
      nodules and in warm nodules than in cold ones. We found significantly higher NIS
      expression in hot and warm nodules than in the surrounding parenchyma. The level
      of NIS expression did not differ significantly between cold nodules and the
      collateral tissues. CONCLUSIONS: Our data indicate that NIS protein participates
      in the development of hyperthyroidism in the course of a nodular goiter. We
      confirm that the functional state of a nodular goiter is determined by NIS
      expression in nodules, not in collateral parenchyma. The low metabolism of cold
      nodules does not simply result from decreased level of NIS protein or its
      defective targeting to the cell membrane. The observation of NIS in the cell
      cytoplasm of hot nodules seems to indicate that the intracellular localization of
      NIS does not determine loss of its activity.

PMID- 17227733
TI  - Myocardial perfusion and ventricular function assessed by SPECT and Gated-SPECT
      in end-stage renal disease patients before and after renal transplant.
AB  - BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in
      end-stage renal disease (ESRD). Renal transplant is known to improve left
      ventricle hypertrophy and systolic dysfunction in selected groups of patients.
      METHODS: We assessed myocardial perfusion, wall motion and functional parameters
      by single photon emission computed tomography (SPECT) and Gated-SPECT in 30
      consecutive ESRD patients with normal coronary angiograms before and after renal
      transplantation. RESULTS: Uremic cardiomyopathy improved significantly after the
      transplant. The proportion of patients with angina decreased from 26 to 0%; the
      frequency of cardiomegaly decreased from 57 to 20% (p <0.01); the frequency of
      segments with perfusion defects decreased from 42.7 to 10.2% (p <0.001); the
      proportion of patients with low left ventricular ejection fraction (LVEF) dropped
      from 53.3 to 20% (p <0.001); and mean LVEF increased from (48.0 +/- 9.7% to 58.2
      +/- 8.2%). Similarly, the proportion of segments showing systolic wall
      thickening, hypokinesia and dyskinesia also decreased significantly after renal
      transplant (p <0.01). CONCLUSIONS: Uremic cardiomyopathy may be potentially
      reversible in patients with normal angiographic coronary arteries after renal
      transplant in a relatively short period of time. SPECT and Gated-SPECT are
      objective gateway methods to determine myocardial perfusion, hypokinesia,
      dyskinesia, and functional parameters (left ventricular ejection fraction and
      systolic wall thickening) and may be useful to establish diagnostic,
      coronariographic, prognostic, and therapeutic indications.

PMID- 17227734
TI  - Correlation between cognitive impairment and prognostic parameters in patients
      with congestive heart failure.
AB  - BACKGROUND: Cognitive impairment has been observed in patients with congestive
      heart failure (CHF). We analyzed in-hospital CHF patients with neuropsychological
      tests attempting to correlate the results with prognostic parameters. METHODS:
      All subjects underwent a mini-mental state examination (MMSE), memory and
      learning tests (Corsi Block-tapping test, Verbal Span test, Prose Memory test,
      Visual Search), anxiety and depression scale test. New York Hospital Association
      (NYHA) class, brain natriuretic peptide (BNP) and left ventricular ejection
      fraction (LVEF) were evaluated. RESULTS: Sixty patients (mean age 65.5 years)
      were analyzed. NYHA class was 2.9 +/- 0.9, LVEF was 32.9 +/- 13.7%, BNP plasma
      level 683.3 +/- 864.3 pg/mL. In 23.3% of cases a pathological MMSE score emerged;
      memory and learning test results were abnormal in 3.4-37%. A positive correlation
      between MMSE and age (r = 0.18, p = 0.01), BNP (r = 0.25, p = 0.02) was observed
      but not between MMSE and years of education, NYHA class and LVEF. The Corsi Block
      tapping test was related to educational duration (r = 0.12, p = 0.02) with a
      positive trend for BNP (r = 0.2, p = 0.07). The Prose Memory test and Visual
      Search were influenced by the patients' educational level (r = 0.36, p = 0.0001;
      r = 0.27, p = 0.0001). CONCLUSIONS: CHF patients manifest an impairment of MMSE
      and memory and learning test performance. In our population MMSE correlates to
      plasma BNP and advanced age.

PMID- 17227735
TI  - Oxypurine and purine nucleoside concentrations in renal vein of allograft are
      potential markers of energy status of renal tissue.
AB  - BACKGROUND: Impairment of organ function derived from ischemia-reperfusion injury
      is an important problem in solid organ transplantation. Cell alterations induced
      by ischemia prime the tissue for subsequent damage that occurs during the
      reperfusion phase. Purine nucleosides and oxypurines are products of adenine
      nucleotides degradation. Reperfusion and reoxygenation are accompanied by
      production of reactive oxygen species and free radicals, which lead to damage of
      graft tissue. The aim of this study was to measure concentrations of adenine
      nucleotides and their metabolites in renal allograft vein as well as in
      recipient's peripheral veins during the reperfusion period and to evaluate their
      usefulness as markers of tissue metabolism in kidney allografts. METHODS: The
      study enrolled 20 renal transplant recipients. The first blood sample was taken
      from the recipient's ulnar vein before anastomosing of the kidney graft's vessels
      with recipient's iliac vessels. Samples were then taken from the renal allograft
      and ulnar veins 5 min after total graft reperfusion measured with an infrared
      camera. High-performance liquid chromatography (HPLC) was performed to measure
      whole blood and plasma concentrations of adenosine triphosphate (ATP), adenosine
      monophosphate (AMP), guanosine (Guo), inosine (Ino), hypoxanthine (Hyp), xanthine
      (Xan), uric acid (UA), and uridine (Urd). RESULTS: Hyp and Xan concentrations
      were significantly increased in renal allograft vein after reperfusion as
      compared with peripheral vein during the pre- and post-reperfusion periods.
      CONCLUSIONS: The results of the present study suggest that differences in Hyp and
      Xan concentrations between renal and peripheral veins reflect metabolic
      alterations in renal tissue during reperfusion and may be useful for graft
      function monitoring during reperfusion.

PMID- 17227736
TI  - Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in
      patients with major depression: impact of antidepressant treatment.
AB  - BACKGROUND: There has been much evidence in recent years that free oxygen
      radicals and nitric oxide (NO) may play an important role in the pathophysiology
      of neuropsychiatric disorders. In this study, we aimed to investigate whether NO,
      xanthine oxidase (XO), superoxide dismutase (SOD), and adenosine deaminase (ADA)
      levels are associated with major depression (MD) and to evaluate the impact of
      antidepressant treatments on NO, SOD, ADA and XO levels in MD. METHODS: Thirty
      six patients who were diagnosed as MD according to DSM-IV criteria and 20 healthy
      controls were included. The serum levels of NO, XO, SOD, and ADA were measured by
      spectrophotometric methods both in patients and controls. Patients were treated
      with antidepressant drugs for 8 weeks. All patients were assessed by Hamilton
      Depression Rating Scale (HDRS) both before and after antidepressant treatment.
      RESULTS: ADA and XO levels of the patients were significantly higher than the
      controls. SOD level of the patients was significantly lower than the controls.
      Although NO levels of the patients were higher than the controls, the difference
      was not statistically significant. There was no correlation between HDRS and the
      parameters studied (SOD, ADA, XO, and NO) of the patients. After 8 weeks of
      antidepressant treatment, ADA and SOD activities were increased, whereas NO and,
      XO levels decreased significantly. CONCLUSIONS: ADA, XO, and SOD activity may
      have a pathophysiological role in MD and may predict prognosis of MD. Activity of
      these enzymes may be used to monitor effects of the antidepressant treatment.

PMID- 17227737
TI  - Cut-off values for anthropometric variables that confer increased risk of type 2
      diabetes mellitus and hypertension in Iraq.
AB  - BACKGROUND: Body mass index (BMI) is often used to reflect total body fat amount
      (general obesity), whereas waist circumference (WC), waist-to-hip ratio (WHpR) or
      waist-to height ratio (WHtR) is used as a surrogate of body fat centralization
      (central obesity). The purpose of the present study was to identify cut-offs for
      BMI and upper-body adiposity (WC, WHpR, and WHtR) that, associated with increased
      risk of type 2 DM and hypertension in Iraqi adults, would be consistent with
      overweight and central adiposity. METHODS: This was a community-based cross
      sectional survey for establishing cut-off values for BMI and upper-body adiposity
      (WC, WHpR or WHtR) associated with increased risk of type 2 DM and hypertension
      from one district in Southern Iraq, Basrah (Abu-Al-khasib). The total number of
      persons involved was 12,986 (6693 men and 6293 women), aged 45.6 +/- 15.7 years.
      RESULTS: The cut-off point in men associated with increased risk of type 2 DM and
      hypertension were BMI 25.4 and 24.9, WC 90 and 95 cm, WHpR 0.92 for both and WHtR
      0.52 and 0.55, respectively. For women, the cut-off point associated with
      increased risk of type 2 DM and hypertension were BMI 26.1 and 26.5, WC 91 and 95
      cm, WHpR 0.91 for both, and for WHtR 0.56 and 0.59, respectively. The best index
      for association with type 2 DM was WHpR with cut-off point of 0.92 for men and
      0.91 for women. For hypertension, the best index is WHtR (with cut-off point of
      0.55 for men and 0.59 for women), whereas the least reliable index was the BMI
      for both type 2 DM and hypertension. CONCLUSIONS: Our finding showed that, in
      Iraqi adults, WHpR has the strongest association with type 2 DM and WHtR for
      hypertension.

PMID- 17227738
TI  - Bone mineral density and its related factors in elderly male Chinese patients
      with type 2 diabetes.
AB  - BACKGROUND: There have been few investigations conducted on the epidemiology and
      risk factors of osteoporosis in patients with diabetes in China. The aim of this
      study was to disclose the percentage and the possible risk factors that influence
      bone mineral density (BMD) in this population. METHODS: One hundred thirty-one
      elderly male patients with type 2 diabetes (73.12 +/- 5.54 years of age, diabetic
      duration 5.28 +/- 3.56 years, HbA(1C) 7.87% +/- 1.82 %), >65 years of age were
      recruited. All subjects were submitted to dual-energy X-ray absorptiometry to
      evaluate the BMD at lumbar spine (LS), femoral neck (FN), and femoral trochanter
      (FT). Fasting blood samples were taken to check hormones and biochemical levels.
      Demographic data were also collected. RESULTS: In the different bone sites
      studied, the percentage of osteoporosis and osteopenia varied in this group of
      patients ranging from 29.0 to 31.3% and 29.0 to 33.6%, respectively. Weight,
      HbA(1C), body mass index, and testosterone were correlated with BMD at all the
      bone sites studied. Weight was the best predictor among the above parameters for
      BMD by linear regression analysis at LS and FN, whereas testosterone was the best
      predictor for BMD at FT. CONCLUSIONS: In the different bone sites studied, the
      percentage of osteoporosis and osteopenia varied ranging from 29.0 to 31.3% and
      29.0 to 33.6%, respectively. Weight was the best predictor for BMD at LS and FN
      and testosterone was the best predictor for BMD at FT. Poor glycemic control was
      correlated with osteoporosis.

PMID- 17227739
TI  - Tropospheric ozone toxicity vs. usefulness of ozone therapy.
AB  - There is a general consensus that continuous inhalation of air polluted with
      ozone is detrimental for the lungs and vital organs. Even if the concentration of
      tropospheric ozone is slightly above the tolerated dose, toxicity ensues owing to
      the cumulative dose inhaled for months. However, in medicine ozone is used as a
      real drug and a precise concentration and therapeutic dosage must be calibrated
      against the antioxidant capacity of blood. As ozone reacts with blood, it
      generates pharmacological messengers such as H(2)O(2) and lipid oxidation
      products (LOPs). These activate several biochemical pathways in blood cells,
      which after reinfusion are responsible for therapeutic activities lasting several
      days. Neither acute nor chronic toxicity has been registered.

PMID- 17227740
TI  - Finally, some light on the 'Pillar of Homeopathy'.

PMID- 17227741
TI  - The diversity of veterinary homeopathy.

PMID- 17227743
TI  - Homeopathic Arnica montana for post-tonsillectomy analgesia: a randomised placebo
      control trial.
AB  - OBJECTIVE: To evaluate the efficacy of Homeopathic Arnica in reducing the
      morbidity following tonsillectomy. METHODS: Randomised double blind, placebo
      controlled trial at a tertiary referral centre. 190 patients over the age of 18
      undergoing tonsillectomy were randomised into intervention and control groups
      receiving either Arnica 30c or identical placebo, 2 tablets 6 times in the first
      post-operative day and then 2 tablets twice a day for the next 7 days. The
      primary outcome measure was the change in pain scores (visual analogue scale)
      recorded by the patient on a questionnaire over 14 days post-operatively;
      Secondary outcome measures were: analgesia consumption, visits to the GP or
      hospital, antibiotic usage, the day on which their swallowing returned to normal
      and the day on which they returned to work. RESULTS: 111 (58.4%) completed
      questionnaires were available for analysis. The Arnica group had a significantly
      larger drop in pain score from day 1 to day 14 (28.3) compared to the placebo
      group (23.8) with p < 0.05. The two groups did not differ significantly on
      analgesic consumption or any of the other secondary outcome measures (number of
      post-operative visits to GP, use of antibiotics and secondary haemorrhage
      readmissions). CONCLUSION: The results of this trial suggest that Arnica montana
      given after tonsillectomy provides a small, but statistically significant,
      decrease in pain scores compared to placebo.

PMID- 17227742
TI  - A systematic review of the quality of homeopathic pathogenetic trials published
      from 1945 to 1995.
AB  - BACKGROUND: The quality of information gathered from homeopathic pathogenetic
      trials (HPTs), also known as 'provings', is fundamental to homeopathy. We
      systematically reviewed HPTs published in six languages (English, German,
      Spanish, French, Portuguese and Dutch) from 1945 to 1995, to assess their quality
      in terms of the validity of the information they provide. METHODS: The literature
      was comprehensively searched, only published reports of HPTs were included.
      Information was extracted by two reviewers per trial using a form with 87 items.
      Information on: medicines, volunteers, ethical aspects, blinding, randomization,
      use of placebo, adverse effects, assessments, presentation of data and number of
      claimed findings were recorded. Methodological quality was assessed by an index
      including indicators of internal and external validity, personal judgement and
      comments of reviewers for each study. RESULTS: 156 HPTs on 143 medicines,
      involving 2815 volunteers, produced 20,538 pathogenetic effects (median 6.5 per
      volunteer). There was wide variation in methods and results. Sample size (median
      15, range 1-103) and trial duration (mean 34 days) were very variable. Most
      studies had design flaws, particularly absence of proper randomization, blinding,
      placebo control and criteria for analysis of outcomes. Mean methodological score
      was 5.6 (range 4-16). More symptoms were reported from HPTs of poor quality than
      from better ones. In 56% of trials volunteers took placebo. Pathogenetic effects
      were claimed in 98% of publications. On average about 84% of volunteers receiving
      active treatment developed symptoms. The quality of reports was in general poor,
      and much important information was not available. CONCLUSIONS: The HPTs were
      generally of low methodological quality. There is a high incidence of
      pathogenetic effects in publications and volunteers but this could be
      attributable to design flaws. Homeopathic medicines, tested in HPTs, appear safe.
      The central question of whether homeopathic medicines in high dilutions can
      provoke effects in healthy volunteers has not yet been definitively answered,
      because of methodological weaknesses of the reports. Improvement of the method
      and reporting of results of HPTs are required. REFERENCES: References to all
      included RCTs are available on-line at.

PMID- 17227744
TI  - The use of homeopathic combination remedy for dengue fever symptoms: a pilot RCT
      in Honduras.
AB  - A double-blind, placebo-controlled randomized trial of a homeopathic combination
      medication for dengue fever was carried out in municipal health clinics in
      Honduras. Sixty patients who met the case definition of dengue (fever plus two
      ancillary symptoms) were randomized to receive the homeopathic medication or
      placebo for 1 week, along with standard conventional analgesic treatment for
      dengue. The results showed no difference in outcomes between the two groups,
      including the number of days of fever and pain as well as analgesic use and
      complication rates. Only three subjects had laboratory confirmed dengue. An
      interesting sinusoidal curve in reported pain scores was seen in the verum group
      that might suggest a homeopathic aggravation or a proving. The small sample size
      makes conclusions difficult, but the results of this study do not suggest that
      this combination homeopathic remedy is effective for the symptoms that are
      characteristic of dengue fever.

PMID- 17227745
TI  - Outcomes from homeopathic prescribing in veterinary practice: a prospective,
      research-targeted, pilot study.
AB  - BACKGROUND AND AIMS: Targeted research development in veterinary homeopathy is
      properly informed by the systematic collection and analysis of relevant clinical
      data obtained by its practitioners. We organised a pilot data collection study,
      in which 8 Faculty of Homeopathy veterinarians collected practice-based clinical
      and outcomes data over a 6-month period. METHODS: A specifically designed Excel
      spreadsheet enabled recording of consecutive clinical appointments under the
      following headings: date; identity of patient and owner (anonymised); age, sex
      and species of patient; medical condition/complaint treated; whether confirmed
      diagnosis, chronic or acute, new or follow-up case; owner-assessed outcome (7
      point Likert scale: -3 to +3) compared with first appointment; homeopathic
      medicine/s prescribed; other medication/s for the condition/complaint.
      Spreadsheets were submitted monthly by e-mail to the project organisers for data
      checking, synthesis and analysis. RESULTS: Practitioners submitted data regularly
      and punctually, and most data cells were completed. 767 individual patients were
      treated (547 dogs, 155 cats, 50 horses, 5 rabbits, 4 guinea-pigs, 2 birds, 2
      goats, 1 cow, and 1 tortoise). Outcome from two or more homeopathic appointments
      per patient condition was obtained in 539 cases (79.8% showing improvement, 6.1%
      deterioration, 11.7% no change; outcome not recorded in 2.4% of follow-ups).
      Strongly positive outcomes (scores of +2 or +3) were achieved in: arthritis and
      epilepsy in dogs and, in smaller numbers, in atopic dermatitis, gingivitis and
      hyperthyroidism in cats. CONCLUSIONS: Systematic recording of data by
      veterinarians in clinical practice is feasible and capable of informing future
      research in veterinary homeopathy. A refined version of the spreadsheet can be
      used in larger-scale research-targeted veterinary data collection.

PMID- 17227746
TI  - Randomised controlled trials of homeopathy in hyperactive children: treatment
      procedure leads to an unconventional study design. Experience with open-label
      homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised,
      double-blind, cross-over trial.
AB  - BACKGROUND: Treatment of patients with attention deficit hyperactivity disorder
      (ADHD) with homeopathy is difficult. The Swiss randomised, placebo controlled,
      cross-over trial in ADHD patients (Swiss ADHD trial) was designed with an open
      label screening phase prior to the randomised controlled phase. During the
      screening phase, the response of each child to successive homeopathic medications
      was observed until the optimal medication was identified. Only children who
      reached a predefined level of improvement participated in the randomised, cross
      over phase. Although the randomised phase revealed a significant beneficial
      effect of homeopathy, the cross-over caused a strong carryover effect diminishing
      the apparent difference between placebo and verum treatment. METHODS: This
      retrospective analysis explores the screening phase data with respect to the risk
      of failure to demonstrate a specific effect of a randomised controlled trial
      (RCT) with randomisation at the start of the treatment. RESULTS: During the
      screening phase, 84% (70/83) of the children responded to treatment and reached
      eligibility for the randomised trial after a median time of 5 months (range 1
      18), with a median of 3 different medications (range 1-9). Thirteen children
      (16%) did not reach eligibility. Five months after treatment start, the
      difference in Conners Global Index (CGI) rating between responders and non
      responders became highly significant (p = 0.0006). Improvement in CGI was much
      greater following the identification of the optimal medication than in the
      preceding suboptimal treatment period (p < 0.0001). CONCLUSIONS: Because of the
      necessity of identifying an optimal medication before response to treatment can
      be expected, randomisation at the start of treatment in an RCT of homeopathy in
      ADHD children has a high risk of failure to demonstrate a specific treatment
      effect, if the observation time is shorter than 12 months.

PMID- 17227747
TI  - Reporting data on homeopathic treatments (RedHot): a supplement to CONSORT.
AB  - When homeopathy is tested in clinical trials, understanding and appraisal is
      likely to be improved if published reports contain details of prescribing
      strategies and treatments. An international Delphi panel was convened to develop
      consensus guidelines for reporting homeopathic methods and treatments. The panel
      agreed 28 treatment- and provider-specific items that supplement the Consolidated
      Standards of Reporting Trials (CONSORT) Statement items 2, 3, 4 and 19. The
      authors recommend these for adoption by authors and journals when reporting
      trials of homeopathy.

PMID- 17227748
TI  - Clinical management of idiopathic epilepsy in dogs with homeopathic Belladonna
      200C: a case series.
AB  - Epilepsy is an important neurological disorder in dogs. Belladonna 200C was
      evaluated in 10 dogs with idiopathic epilepsy. During the seizure phase, 3-4
      drops of Belladonna 200C were administered orally at 15 min intervals until
      considerable reduction in seizure activity, then four times daily. Four dogs with
      head shaking syndrome in addition to seizures were given Cocculus 6C, 3-4 drops
      orally weekly for 3 months in addition. Numbers of fits reduced to 2-3 during
      first 2 weeks post-therapy and then became occasional in next 2 weeks. With
      continuation of Belladonna therapy, no fits were observed during 2-7 months
      follow-up. In two cases epileptic fits reappeared within 15-25 days of cessation
      of therapy. Belladonna therapy was resumed and seizure control was again
      achieved. Owners were advised to continue the therapy at least twice daily until
      there were no fits for 2-3 months. Liver specific enzymes were monitored, no
      abnormalities were observed.

PMID- 17227749
TI  - Homeopathic treatment for infertility in a prize Nelore bull.
AB  - Treatments for infertility in bulls are not described in homeopathic literature.
      A few treatments, such as changing the protein content of the diet, giving extra
      minerals, etc have been proposed. This case report describes homeopathic
      treatment for infertility in a prize bull. A Nelore bull, considered infertile
      for 3 years, was treated with homeopathic Pulsatilla nigricans 200 CH. Decreased
      total sperm defects, increased sperm motility and a very impressive increased
      number of doses of semen produced were observed. The bull relapsed after
      treatment was withdrawn, but again responded when it was resumed. Since only one
      animal was observed one cannot assume that the observed changes were due only to
      this treatment. Further studies may establish the real benefits of a homeopathic
      medicine in bull infertility.

PMID- 17227750
TI  - The history of MSM--homeopathy and natural medicines.

PMID- 17227751
TI  - 20 years ago: The British Homoeopathic Journal, January 1987.

PMID- 17227753
TI  - Patient compliance.

PMID- 17227752
TI  - NSAIDs, Myocardial infarction, rebound effect and similitude.

PMID- 17227754
TI  - Mutational study of heparan sulfate 2-O-sulfotransferase and chondroitin sulfate
      2-O-sulfotransferase.
AB  - Heparan sulfate (HS) and chondroitin sulfate (CS) are highly sulfated
      polysaccharides with a wide range of biological functions. Heparan sulfate 2-O
      sulfotransferase (HS-2OST) transfers the sulfo group from 3'-phosphoadenosine 5'
      phosphosulfate (PAPS) to the 2-OH position of the hexauronic acid that is
      adjacent to N-sulfated glucosamine, whereas chondroitin sulfate 2-O
      sulfotransferase (CS-2OST) transfers the sulfo group to the hexauronic acid that
      is adjacent to N-acetylated galactosamine. Here we report a systematic
      mutagenesis study of HS-2OST and CS-2OST based on their structural homology to
      estrogen sulfotransferase and HS 3-O-sulfotransferase isoform 3 (3-OST3), for
      which crystal structures exist. We have identified six residues possibly involved
      in binding to PAPS. HS-2OST carrying mutations of these residues lacks
      sulfotransferase activity and the ability to bind 3'-phosphoadenosine 5'
      phosphate, a PAPS analogue, as determined by isothermal titration calorimetry.
      Similar residues involved in binding to PAPS were also identified in CS-2OST.
      Additional residues that participate in carbohydrate substrate binding were also
      identified in both enzymes. Mutations at these residues led to the loss of
      sulfotransferase activity but maintained the ability to bind to phosphoadenosine
      5'-phosphate. The catalytic function of HS-2OST appears to involve two histidine
      residues (His140 and His142), whereas only one histidine (His168) of CS 2-OST is
      likely to be critical. This unique feature of HS 2-OST catalytic residues
      directed us to characterize the Drosophila heparan sulfate 2-O-sulfotransferase.
      The results from this study provide insight into the differences and similarities
      various residues play in the biological roles of the HS-2OST and CS-2OST enzymes.

PMID- 17227755
TI  - Interaction between human cathepsins K, L, and S and elastins: mechanism of
      elastinolysis and inhibition by macromolecular inhibitors.
AB  - Proteolytic degradation of elastic fibers is associated with a broad spectrum of
      pathological conditions such as atherosclerosis and pulmonary emphysema. We have
      studied the interaction between elastins and human cysteine cathepsins K, L, and
      S, which are known to participate in elastinolytic activity in vivo. The enzymes
      showed distinctive preferences in degrading elastins from bovine neck ligament,
      aorta, and lung. Different susceptibility of these elastins to proteolysis was
      attributed to morphological differences observed by scanning electron microscopy.
      Kinetics of cathepsin binding to the insoluble substrate showed that the process
      occurs in two steps. The enzyme is initially adsorbed on the elastin surface in a
      nonproductive manner and then rearranges to form a catalytically competent
      complex. In contrast, soluble elastin is bound directly in a catalytically
      productive manner. Studies of enzyme partitioning between the phases showed that
      cathepsin K favors adsorption on elastin; cathepsin L prefers the aqueous
      environment, and cathepsin S is equally distributed among both phases. Our
      results suggest that elastinolysis by cysteine cathepsins proceeds in cycles of
      enzyme adsorption, binding of a susceptible peptide moiety, hydrolysis, and
      desorption. Alternatively, the enzyme may also form a new catalytic complex
      without prior desorption and re-adsorption. In both cases the active center of
      the enzymes remains at least partly accessible to inhibitors. Elastinolytic
      activity was readily abolished by cystatins, indicating that, unlike enzymes such
      as leukocyte elastase, pathological elastinolytic cysteine cathepsins might
      represent less problematic drug targets. In contrast, thyropins were relatively
      inefficient in preventing elastinolysis by cysteine cathepsins.

PMID- 17227756
TI  - Post-transcriptional up-regulation of ADAM17 upon epidermal growth factor
      receptor activation and in breast tumors.
AB  - ADAM17 is a transmembrane metalloprotease involved in the proteolytic release of
      the extracellular domain of many cell surface molecules, a process known as
      ectodomain shedding. Despite its likely participation in tumor progression and
      its current consideration as a therapeutic target, very little is known about the
      regulation of the expression of ADAM17. Here we show that long term treatment
      with epidermal growth factor (EGF) leads to a marked increase in the levels of
      ADAM17. EGF receptor activation does not affect the levels of the mRNA that
      encodes for, or the rate of synthesis of, ADAM17 but increases its half-life. The
      effect of EGF is biologically relevant because it increases the shedding of
      several substrates of ADAM17, including the desmosomal cadherin Dsg-2. Analysis
      of protein and mRNA levels in mammary tumor samples shows that in vivo the levels
      of ADAM17 can also be controlled post-transcriptionally. Finally, we show that
      both the shed extracellular domains of Dsg-2 and ADAM17 are frequently expressed
      in tumors, further supporting the participation of the metalloprotease in
      malignant progression.

PMID- 17227757
TI  - Human biliverdin reductase, a previously unknown activator of protein kinase C
      betaII.
AB  - Human biliverdin reductase (hBVR), a dual specificity kinase (Ser/Thr/Tyr) is, as
      protein kinase C (PKC) betaII, activated by insulin and free radicals (Miralem,
      T., Hu, Z., Torno, M. D., Lelli, K. M., and Maines, M. D. (2005) J. Biol. Chem.
      280, 17084-17092; Lerner-Marmarosh, N., Shen, J., Torno, M. D., Kravets, A., Hu,
      Z., and Maines, M. D. (2005) Proc. Natl. Acad. Sci. U. S. A. 102, 7109-7114).
      Here, by using 293A cells co-transfected with pcDNA3-hBVR and PKC betaII
      plasmids, we report the co-immunoprecipitation of the proteins and co
      purification in the glutathione S-transferase (GST) pulldown assay. hBVR and PKC
      betaII, but not the reductase and PKC zeta, transphosphorylated in assay systems
      supportive of activity of only one of the kinases. PKC betaII K371R mutant
      protein ("kinase-dead") was also a substrate for hBVR. The reductase increased
      the Vmax but not the apparent Km values of PKC betaII for myelin basic protein;
      activation was independent of phospholipids and extended to the phosphorylation
      of S2, a PKC-specific substrate. The increase in substrate phosphorylation was
      blocked by specific inhibitors of conventional PKCs and attenuated by sihBVR. The
      effect of the latter could be rescued by subsequent overexpression of hBVR. To a
      large extent, the activation was a function of the hBVR N-terminal chain of
      valines and intact ATP-binding site and the cysteine-rich C-terminal segment. The
      cobalt protoporphyrin-activated hBVR phosphorylated a threonine in a peptide
      corresponding to the Thr500 in the human PKC betaII activation loop. Neither
      serine nor threonine residues in peptides corresponding to other phosphorylation
      sites of the PKC betaII nor PKC zeta activation loop-derived peptides were
      substrates. The phosphorylation of Thr500 was confirmed by immunoblotting of
      hBVR.PKC betaII immunocomplex. The potential biological relevance of the hBVR
      activation of PKC betaII was suggested by the finding that in cells transfected
      with the PKC betaII, hBVR augmented phorbol myristate acetate-mediated c-fos
      expression, and infection with sihBVR attenuated the response. Also, in cells
      overexpressing hBVR and PKC betaII, as well as in untransfected cells, upon
      treatment with phorbol myristate acetate, the PKC translocated to the plasma
      membrane and co-localized with hBVR. hBVR activation of PKC betaII underscores
      its potential function in propagation of signals relayed through PKCs.

PMID- 17227758
TI  - The role of diacylglycerol lipase in constitutive and angiotensin AT1 receptor
      stimulated cannabinoid CB1 receptor activity.
AB  - The cannabinoid CB1 receptor (CB1R) is a G protein-coupled receptor, which
      couples to the Gi/o family of heterotrimeric G proteins. The receptor displays
      both basal and agonist-induced signaling and internalization. Although basal
      activity of CB1Rs is attributed to constitutive (agonist-independent) receptor
      activity, studies in neurons suggested a role of postsynaptic endocannabinoid
      (eCB) release in the persistent activity of presynaptic CB1Rs. To elucidate the
      role of eCBs in basal CB1R activity, we have investigated the role of
      diacylglycerol lipase (DAGL) in this process in Chinese hamster ovary (CHO)
      cells, which are not targeted specifically with eCBs. Agonist-induced G protein
      activation was determined by detecting dissociation G protein subunits expressed
      in CHO cells with bioluminescence resonance energy transfer (BRET), after
      labeling the alpha and beta subunits with Renilla luciferase and enhanced yellow
      fluorescent protein (EYFP), respectively. Preincubation of the cells with
      tetrahydrolipstatin (THL), a known inhibitor of DAGLs, caused inhibition of the
      basal activity of CB1R. Moreover, preincubation of CHO and cultured hippocampal
      neurons with THL increased the number of CB1Rs on the cell membrane, which
      reflects its inhibitory action on CB1R internalization in non-simulated cells. In
      CHO cells co-expressing CB1R and angiotensin AT1 receptors, angiotensin II
      induced Go protein activation that was blocked by both a CB1R antagonist and THL.
      These data indicate that cell-derived eCB mediators have a general role in the
      basal activity of CB1Rs in non-neural cells and neurons, and that this mechanism
      can be stimulated by AT1 receptor activation.

PMID- 17227759
TI  - Ganglioside GD1a is an essential coreceptor for Toll-like receptor 2 signaling in
      response to the B subunit of type IIb enterotoxin.
AB  - Innate recognition and signaling by Toll-like receptors (TLRs) is facilitated by
      functionally associated coreceptors, although the cooperativity mechanisms
      involved are poorly understood. As a model we investigated TLR2 interactions with
      the GD1a ganglioside binding subunit of type IIb Escherichia coli enterotoxin (LT
      IIb-B(5)). Both LT-IIb-B(5) and a GD1a binding-defective mutant (LT-IIb
      B(5)(T13I)) could modestly bind to TLR2, but only the wild-type molecule
      displayed a dramatic increase in TLR2 binding activity in the presence of GD1a
      (although not in the presence of irrelevant gangliosides). Moreover, fluorescence
      resonance energy transfer experiments indicated that LT-IIb-B(5) induces lipid
      raft recruitment of TLR2 and TLR1 and their clustering with GD1a, in contrast to
      the GD1a binding-defective mutant, which moreover fails to activate TLR2
      signaling. LT-IIb-B(5)-induced cell activation was critically dependent upon the
      Toll/IL-1 receptor domain-containing adaptor protein, which was induced to
      colocalize with TLR2 and GD1a, as shown by confocal imaging. Therefore, GD1a
      provides TLR2 coreceptor function by enabling the ligand to recruit, bind, and
      activate TLR2. These findings establish a model of TLR2 coreceptor function and,
      moreover, suggest novel mechanisms of adjuvanticity by non-toxic derivatives of
      type II enterotoxins dependent upon GD1a/TLR2 cooperative activity.

PMID- 17227760
TI  - The crystal structure of Atg3, an autophagy-related ubiquitin carrier protein
      (E2) enzyme that mediates Atg8 lipidation.
AB  - Atg3 is an E2-like enzyme that catalyzes the conjugation of Atg8 and
      phosphatidylethanolamine (PE). The Atg8-PE conjugate is essential for autophagy,
      which is the bulk degradation process of cytoplasmic components by the
      vacuolar/lysosomal system. We report here the crystal structure of Saccharomyces
      cerevisiae Atg3 at 2.5-A resolution. Atg3 has an alpha/beta-fold, and its core
      region is topologically similar to canonical E2 enzymes. Atg3 has two regions
      inserted in the core region, one of which consists of approximately 80 residues
      and has a random coil structure in solution and another with a long alpha-helical
      structure that protrudes from the core region as far as 30 A. In vivo and in
      vitro analyses suggested that the former region is responsible for binding Atg7,
      an E1-like enzyme, and that the latter is responsible for binding Atg8. A sulfate
      ion was bound near the catalytic cysteine of Atg3, suggesting a possible binding
      site for the phosphate moiety of PE. The structure of Atg3 provides a molecular
      basis for understanding the unique lipidation reaction that Atg3 carries out.

PMID- 17227761
TI  - Modification of lipopolysaccharide with colanic acid (M-antigen) repeats in
      Escherichia coli.
AB  - Colanic acid (CA) or M-antigen is an exopolysaccharide produced by many
      enterobacteria, including the majority of Escherichia coli strains. Unlike other
      capsular polysaccharides, which have a close association with the bacterial
      surface, CA forms a loosely associated saccharide mesh that coats the bacteria,
      often within biofilms. Herein we show that a highly mucoid strain of E. coli K-12
      ligates CA repeats to a significant proportion of lipopolysaccharide (LPS) core
      acceptor molecules, forming the novel LPS glycoform we call MLPS.MLPS
      biosynthesis is dependent upon (i) CA induction, (ii) LPS core biosynthesis, and
      (iii) the O-antigen ligase WaaL. Compositional analysis, mass spectrometry, and
      nuclear magnetic resonance spectroscopy of a purified MLPS sample confirmed the
      presence of a CA repeat unit identical in carbohydrate sequence, but differing at
      multiple positions in anomeric configuration and linkage, from published
      structures of extracellular CA. The attachment point was identified as O-7 of the
      L-glycero-D-manno-heptose of the outer LPS core, the same position used for O
      antigen ligation. When O-antigen biosynthesis was restored in the K-12 background
      and grown under conditions meeting the above specifications, only MLPS was
      observed, suggesting E. coli can reversibly change its proximal covalently linked
      cell surface polysaccharide coat from O-antigen to CA in response to certain
      environmental stimuli. The identification of MLPS has implications for potential
      underlying mechanisms coordinating the synthesis of various surface
      polysaccharides.

PMID- 17227762
TI  - Evidence for the involvement of carbon-centered radicals in the induction of
      apoptotic cell death by artemisinin compounds.
AB  - Artemisinin and its derivatives are currently recommended as first-line
      antimalarials in regions where Plasmodium falciparum is resistant to traditional
      drugs. The cytotoxic activity of these endoperoxides toward rapidly dividing
      human carcinoma cells and cell lines has been reported, and it is hypothesized
      that activation of the endoperoxide bridge by an iron(II) species, to form C
      centered radicals, is essential for cytotoxicity. The studies described here have
      utilized artemisinin derivatives, dihydroartemisinin, 10beta-(p
      bromophenoxy)dihydroartemisinin, and 10beta-(p-fluorophenoxy)dihydroartemisinin,
      to determine the chemistry of endoperoxide bridge activation to reactive
      intermediates responsible for initiating cell death and to elucidate the
      molecular mechanism of cell death. These studies have demonstrated the selective
      cytotoxic activity of the endoperoxides toward leukemia cell lines (HL-60 and
      Jurkat) over quiescent peripheral blood mononuclear cells. Deoxy-10beta-(p
      fluorophenoxy)dihydroartemisinin, which lacks the endoperoxide bridge, was 50-
      and 130-fold less active in HL-60 and Jurkat cells, respectively, confirming the
      importance of this functional group for cytotoxicity. We have shown that chemical
      activation is responsible for cytotoxicity by using liquid chromatography-mass
      spectrometry analysis to monitor endoperoxide activation by measurement of a
      stable rearrangement product of endoperoxide-derived radicals, which was formed
      in sensitive HL-60 cells but not in insensitive peripheral blood mononuclear
      cells. In HL-60 cells the endoperoxides induce caspase-dependent apoptotic cell
      death characterized by concentration- and time-dependent mitochondrial membrane
      depolarization, activation of caspases-3 and -7, sub-G(0)/G(1) DNA formation, and
      attenuation by benzyloxycarbonyl-VAD-fluoromethyl ketone, a caspase inhibitor.
      Overall, these results indicate that endoperoxide-induced cell death is a
      consequence of activation of the endoperoxide bridge to radical species, which
      triggers caspase-dependent apoptosis.

PMID- 17227763
TI  - Pathogen recognition by Toll-like receptor 2 activates Weibel-Palade body
      exocytosis in human aortic endothelial cells.
AB  - The endothelial cell-specific granule Weibel-Palade body releases vasoactive
      substances capable of modulating vascular inflammation. Although innate
      recognition of pathogens by Toll-like receptors (TLRs) is thought to play a
      crucial role in promotion of inflammatory responses, the molecular basis for
      early-phase responses of endothelial cells to bacterial pathogens has not fully
      been understood. We here report that human aortic endothelial cells respond to
      bacterial lipoteichoic acid (LTA) and synthetic bacterial lipopeptides, but not
      lipopolysaccharide or peptidoglycan, to induce Weibel-Palade body exocytosis,
      accompanied by release or externalization of the storage components von
      Willebrand factor and P-selectin. LTA could activate rapid Weibel-Palade body
      exocytosis through a TLR2- and MyD88-dependent mechanism without de novo protein
      synthesis. This process was at least mediated through MyD88-dependent
      phosphorylation and activation of phospholipase Cgamma. Moreover, LTA activated
      interleukin-1 receptor-associated kinase-1-dependent delayed exocytosis with de
      novo protein synthesis and phospholipase Cgamma-dependent activation of the NF
      kappaB pathway. Increased TLR2 expression by transfection or interferon-gamma
      treatment increased TLR2-mediated Weibel-Palade body exocytosis, whereas reduced
      TLR2 expression under laminar flow decreased the response. Thus, we propose a
      novel role for TLR2 in induction of a primary proinflammatory event in aortic
      endothelial cells through Weibel-Palade body exocytosis, which may be an
      important step for linking innate recognition of bacterial pathogens to vascular
      inflammation.

PMID- 17227764
TI  - A multicopper ferroxidase involved in iron binding to transferrins in Dunaliella
      salina plasma membranes.
AB  - The halotolerant alga Dunaliella salina is unique among plants in that it
      utilizes a transferrin (TTf) to mediate iron acquisition (Fisher, M., Zamir, A.,
      and Pick, U. (1998) J. Biol. Chem. 273, 17553-17558). Two new proteins that are
      induced by iron deprivation were identified in plasma membranes of D. salina as
      follows: a multicopper ferroxidase termed D-Fox and an internally duplicated
      glycoprotein (p130B). D-Fox and p130B are accessible to glycolytic, proteolytic,
      and biotin surface tagging treatments, suggesting that they are surface-exposed
      glycoproteins. Induction of D-Fox was also manifested by ferroxidase activity in
      plasma membrane preparations. These results are puzzling because ferroxidases in
      yeast and in Chlamydomonas reinhardtii function in redox-mediated iron uptake, a
      mechanism that is not known to operate in D. salina. Two lines of evidence
      suggest that D-Fox and p130B interact with D. salina triplicated transferrin
      (TTf). First, chemical cross-linking combined with mass spectroscopy analysis
      showed that D-Fox and p130B associate with TTf and with another plasma membrane
      transferrin. Second, detergent-solubilized D-Fox and p130B comigrated on blue
      native gels with plasma membrane transferrins. 59Fe autoradiography indicated
      that this complex binds Fe3+ ions. Also, the induction of D-Fox and p130B is
      kinetically correlated with enhanced iron binding and uptake activities. These
      results suggest that D-Fox and p130B associate with plasma membrane transferrins
      forming a complex that enhances iron binding and iron uptake. We propose that the
      function of D-Fox in D. salina has been modified during evolution from redox
      mediated to transferrin-mediated iron uptake, following a gene transfer event of
      transferrins from an ancestral animal cell.

PMID- 17227765
TI  - Aminosulfonate modulated pH-induced conformational changes in connexin26
      hemichannels.
AB  - Gap junction channels regulate cell-cell communication by passing metabolites,
      ions, and signaling molecules. Gap junction channel closure in cells by
      acidification is well documented; however, it is unknown whether acidification
      affects connexins or modulating proteins or compounds that in turn act on
      connexins. Protonated aminosulfonates directly inhibit connexin channel activity
      in an isoform-specific manner as shown in previously published studies. High
      resolution atomic force microscopy of force-dissected connexin26 gap junctions
      revealed that in HEPES buffer, the pore was closed at pH < 6.5 and opened
      reversibly by increasing the pH to 7.6. This pH effect was not observed in non
      aminosulfonate buffers. Increasing the protonated HEPES concentration did not
      close the pore, indicating that a saturation of the binding sites occurs at 10 mM
      HEPES. Analysis of the extracellular surface topographs reveals that the pore
      diameter increases gradually with pH. The outer connexon diameter remains
      unchanged, and there is a approximately 6.5 degrees rotation in connexon lobes.
      These observations suggest that the underlying mechanism closing the pore is
      different from an observed Ca2+-induced closure.

PMID- 17227766
TI  - Junctional adhesion molecule-C promotes metastatic potential of HT1080 human
      fibrosarcoma.
AB  - The junctional adhesion molecule (JAM) family is a key molecule in a process
      called transendothelial migration or diapedesis. Here, we report implications of
      JAM-C in cancer metastasis. We first determined the mRNA expression of JAMs in 19
      kinds of cancer cell lines. JAM-C was expressed in most of tumors having potent
      metastatic properties. Especially in murine K-1735 melanoma cell lines, the
      highly metastatic sublines (M2 and X21) strongly expressed JAM-C when compared
      with the poorly metastatic ones (C-10 and C23). Next, we investigated the role of
      JAM-C in cancer metastasis by using human JAM-C (hJAM-C) gene-transfected HT1080
      fibrosarcoma cells. In comparison with mock-transfected HT1080 cells, these cells
      showed a significant increase in the adhesion to various extracellular substrates
      and the invasion across a Matrigel-coated membrane. The knockdown of hJAM-C using
      small interfering RNA resulted in the suppression of both the adhesion and the
      invasion of HT1080 cells, suggesting that endogenous hJAM-C might be involved in
      tumor metastasis. Finally, we studied the role of hJAM-C in an in vivo
      experimental metastatic model. The results showed that the overexpression of hJAM
      C in HT1080 cells significantly decreased the life spans of the tumorbearing
      mice. In contrast, the knockdown of hJAM-C in HT1080 cells suppressed the weight
      gain of the lungs with metastatic colonies. We conclude that the expression of
      JAM-C promotes metastasis by enhancing both the adhesion of cancer cells to
      extracellular matrices and the subsequent invasion.

PMID- 17227767
TI  - Anandamide protects from low serum-induced apoptosis via its degradation to
      ethanolamine.
AB  - Anandamide (AEA) is a lipid molecule belonging to the family of endocannabinoids.
      Various studies report neuroprotective activity of AEA against toxic insults,
      such as ischemic conditions and excitotoxicity, whereas some show that AEA has
      pro-apoptotic effects. Here we have shown that AEA confers a protective activity
      in N18TG2 murine neuroblastoma cells subjected to low serum-induced apoptosis. We
      have demonstrated that the protection from apoptosis by AEA is not mediated via
      the CB1 receptor, the CB2 receptor, or the vanilloid receptor 1. Interestingly,
      breakdown of AEA by fatty acid amide hydrolase is required for the protective
      effect of AEA. Furthermore, the ethanolamine (EA) generated in this reaction is
      the metabolite responsible for the protective response. The elevation in the
      levels of reactive oxygen species during low serum-induced apoptosis is not
      affected by AEA or EA. On the other hand, AEA and EA reduce caspase 3/7 activity,
      and AEA attenuates the cleavage of PARP-1. Taken together, our results
      demonstrate a role for AEA and EA in the protection against low serum-induced
      apoptosis.

PMID- 17227768
TI  - MAP4K4 gene silencing in human skeletal muscle prevents tumor necrosis factor
      alpha-induced insulin resistance.
AB  - Tumor necrosis factor-alpha (TNF-alpha) induces skeletal muscle insulin
      resistance by impairing insulin signaling events involved in GLUT4 translocation.
      We tested whether mitogenic-activated protein kinase kinase kinase kinase isoform
      4 (MAP4K4) causes the TNF-alpha-induced negative regulation of extracellular
      signal-regulated kinase-1/2 (ERK-1/2), c-Jun NH2-terminal kinase (JNK), and the
      insulin receptor substrate-1 (IRS-1) on the insulin signaling pathway governing
      glucose metabolism. Using small interfering RNA (siRNA) to suppress the
      expression of MAP4K4 protein 85% in primary human skeletal muscle cells, we
      provide evidence that TNF-alpha-induced insulin resistance on glucose uptake was
      completely prevented. MAP4K4 silencing inhibited TNF-alpha-induced negative
      signaling inputs by preventing excessive JNK and ERK-1/2 phosphorylation, as well
      as IRS-1 serine phosphorylation. These results highlight the MAPK4K4/JNK/ERK/IRS
      module in the negative regulation of insulin signaling to glucose transport in
      response to TNF-alpha. Depletion of MAP4K4 also prevented TNF-alpha-induced
      insulin resistance on Akt and the Akt substrate 160 (AS160), providing evidence
      that appropriate insulin signaling inputs for glucose metabolism were rescued.
      Silencing of MAP2K1 and MAP2K4, signaling proteins downstream of MAP4K4,
      recapitulated the effect of MAP4K4 siRNA in TNF-alpha-treated cells. Thus,
      strategies to inhibit MAP4K4 may be efficacious in the prevention of TNF-alpha
      induced inhibitory signals that cause skeletal muscle insulin resistance on
      glucose metabolism in humans. Moreover, in myotubes from insulin-resistant type
      II diabetic patients, siRNA against MAP4K4, MAP2K4, or MAP2K1 restored insulin
      action on glucose uptake to levels observed in healthy subjects. Collectively,
      our results demonstrate that MAP4K4 silencing prevents insulin resistance in
      human skeletal muscle and restores appropriate signaling inputs to enhance
      glucose uptake.

PMID- 17227769
TI  - Restoration of liver mass after injury requires proliferative and not embryonic
      transcriptional patterns.
AB  - Normal adult liver is uniquely capable of renewal and repair after injury.
      Whether this response represents simple hyperplasia of various liver elements or
      requires recapitulation of the genetic program of the developing liver is not
      known. To study these possibilities, we examined transcriptional programs of
      adult liver after partial hepatectomy and contrasted these with developing
      embryonic liver. Principal component analysis demonstrated that the time series
      of gene expression during liver regeneration does not segregate according to
      developmental transcription patterns. Gene ontology analysis revealed that liver
      restoration after hepatectomy and liver development differ dramatically with
      regard to transcription factors and chromatin structure modification. In
      contrast, the tissues are similar with regard to proliferation-associated genes.
      Consistent with these findings, real-time polymerase chain reaction showed
      transcription factors known to be important in liver development are not induced
      during liver regeneration. These three lines of evidence suggest that at a
      transcriptional level restoration of liver mass after injury is best described as
      hepatocyte hyperplasia and not true regeneration. We speculate this novel pattern
      of gene expression may underlie the unique capacity of the liver to repair itself
      after injury.

PMID- 17227771
TI  - gamma-Secretase-mediated release of the low density lipoprotein receptor-related
      protein 1B intracellular domain suppresses anchorage-independent growth of
      neuroglioma cells.
AB  - The low density lipoprotein receptor related protein 1B (LRP1B) is a large
      endocytic receptor that was first identified as a candidate tumor suppressor
      gene. In the current investigation we demonstrate that LRP1B undergoes regulated
      intramembrane proteolysis in a gamma-secretase-dependent process. The released
      intracellular domain (ICD) then translocates to the nucleus via a nuclear
      localization signal that is present within this domain. ICD release first
      requires shedding of the LRP1B ectodomain, which appears to be catalyzed by a
      member of the metalloproteinase family. Employing site-directed mutagenesis
      studies, we identified lysine residues 4432 and 4435 and arginine 4442 as key
      amino acids important for ectodomain shedding of LRP1B. We also demonstrate that
      an LRP1B minireceptor as well as the ICD domain alone suppresses anchorage
      independent growth of LRP1B-deficient neuroglioma cells (H4 cells).
      Interestingly, abrogating ectodomain shedding resulted in a loss of the ability
      of LRP1B minireceptors to suppress anchorage-independent growth. Together, these
      studies reveal that LRP1B has tumor suppression function that is mediated by
      proteolytic processing of the receptor resulting in ICD release.

PMID- 17227770
TI  - Phorbol esters induce intracellular accumulation of the anti-apoptotic protein
      PED/PEA-15 by preventing ubiquitinylation and proteasomal degradation.
AB  - Phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes
      (PED/PEA)-15 is an anti-apoptotic protein whose expression is increased in
      several cancer cells and following experimental skin carcinogenesis. Exposure of
      untransfected C5N keratinocytes and transfected HEK293 cells to phorbol esters
      (12-O-tetradecanoylphorbol-13-acetate (TPA)) increased PED/PEA-15 cellular
      content and enhanced its phosphorylation at serine 116 in a time-dependent
      fashion. Ser-116 --> Gly (PED(S116G)) but not Ser-104 --> Gly (PED(S104G))
      substitution almost completely abolished TPA regulation of PED/PEA-15 expression.
      TPA effect was also prevented by antisense inhibition of protein kinase C (PKC)
      zeta and by the expression of a dominant-negative PKC-zeta mutant cDNA in HEK293
      cells. Similar to long term TPA treatment, overexpression of wild-type PKC-zeta
      increased cellular content and phosphorylation of WT-PED/PEA-15 and PED(S104G)
      but not of PED(S116G). These events were accompanied by the activation of Ca2+
      calmodulin kinase (CaMK) II and prevented by the CaMK blocker, KN-93. At
      variance, the proteasome inhibitor lactacystin mimicked TPA action on PED/PEA-15
      intracellular accumulation and reverted the effects of PKC-zeta and CaMK
      inhibition. Moreover, we show that PED/PEA-15 bound ubiquitin in intact cells.
      PED/PEA-15 ubiquitinylation was reduced by TPA and PKC-zeta overexpression and
      increased by KN-93 and PKC-zeta block. Furthermore, in HEK293 cells expressing
      PED(S116G), TPA failed to prevent ubiquitin-dependent degradation of the protein.
      Accordingly, in the same cells, TPA-mediated protection from apoptosis was
      blunted. Taken together, our results indicate that TPA increases PED/PEA-15
      expression at the post-translational level by inducing phosphorylation at serine
      116 and preventing ubiquitinylation and proteosomal degradation.

PMID- 17227772
TI  - Chronic hexosamine flux stimulates fatty acid oxidation by activating AMP
      activated protein kinase in adipocytes.
AB  - The hexosamine biosynthesis pathway (HBP) serves as a nutrient sensor and has
      been implicated in the development of type 2 diabetes. We previously demonstrated
      that fatty acid oxidation was enhanced in transgenic mouse adipocytes, wherein
      the rate-limiting enzyme of the HBP, glutamine:fructose-6-phosphate
      amidotransferase (GFA), was overexpressed. To explore the molecular mechanism of
      the HBP-induced fatty acid oxidation in adipocytes, we studied AMP-activated
      protein kinase (AMPK), an energy sensor that stimulates fatty acid oxidation by
      regulating acetyl-CoA carboxylase (ACC) activity. Phosphorylation and activity of
      AMPK were increased in transgenic fat pads and in 3T3L1 adipocytes treated with
      glucosamine to stimulate hexosamine flux. Glucosamine also stimulated
      phosphorylation of ACC and fatty acid oxidation in 3T3L1 adipocytes, and these
      stimulatory effects were diminished by adenovirus-mediated expression of a
      dominant negative AMPK in 3T3L1 adipocytes. Conversely, blocking the HBP with a
      GFA inhibitor reduced AMPK activity, ACC phosphorylation, and fatty acid
      oxidation. These changes are not explained by alterations in the cellular AMP/ATP
      ratio. Further demonstrating that AMPK is regulated by the HBP, we found that
      AMPK was recognized by succinylated wheat germ agglutinin, which specifically
      binds O-GlcNAc. The levels of AMPK in succinylated wheat germ agglutinin
      precipitates correlated with hexosamine flux in mouse fat pads and 3T3L1
      adipocytes. Moreover, removal of O-GlcNAc by hexosaminidase reduced AMPK
      activity. We conclude that chronically high hexosamine flux stimulates fatty acid
      oxidation by activating AMPK in adipocytes, in part through O-linked
      glycosylation.

PMID- 17227773
TI  - Membrane-permeable calmodulin inhibitors (e.g. W-7/W-13) bind to membranes,
      changing the electrostatic surface potential: dual effect of W-13 on epidermal
      growth factor receptor activation.
AB  - Membrane-permeable calmodulin inhibitors, such as the napthalenesulfonamide
      derivatives W-7/W-13, trifluoperazine, and calmidazolium, are used widely to
      investigate the role of calcium/calmodulin (Ca2+/CaM) in living cells. If two
      chemically different inhibitors (e.g. W-7 and trifluoperazine) produce similar
      effects, investigators often assume the effects are due to CaM inhibition. Zeta
      potential measurements, however, show that these amphipathic weak bases bind to
      phospholipid vesicles at the same concentrations as they inhibit Ca2+/CaM; this
      suggests that they also bind to the inner leaflet of the plasma membrane,
      reducing its negative electrostatic surface potential. This change will cause
      electrostatically bound clusters of basic residues on peripheral (e.g. Src and K
      Ras4B) and integral (e.g. epidermal growth factor receptor (EGFR)) proteins to
      translocate from the membrane to the cytoplasm. We measured inhibitor-mediated
      translocation of a simple basic peptide corresponding to the calmodulin-binding
      juxtamembrane region of the EGFR on model membranes; W-7/W-13 causes
      translocation of this peptide from membrane to solution, suggesting that caution
      must be exercised when interpreting the results obtained with these inhibitors in
      living cells. We present evidence that they exert dual effects on
      autophosphorylation of EGFR; W-13 inhibits epidermal growth factor-dependent EGFR
      autophosphorylation under different experimental conditions, but in the absence
      of epidermal growth factor, W-13 stimulates autophosphorylation of the receptor
      in four different cell types. Our interpretation is that the former effect is due
      to W-13 inhibition of Ca2+/CaM, but the latter results could be due to binding of
      W-13 to the plasma membrane.

PMID- 17227774
TI  - Fungal peptide Destruxin A plays a specific role in suppressing the innate immune
      response in Drosophila melanogaster.
AB  - Destruxins are a class of insecticidal, anti-viral, and phytotoxic cyclic
      depsipeptides that are also studied for their toxicity to cancer cells. They are
      produced by various fungi, and a direct relationship has been established between
      Destruxin production and the virulence of the entomopathogen Metarhizium
      anisopliae. Aside from opening calcium channels, their in vivo mode of action
      during pathogenesis remains largely uncharacterized. To better understand the
      effects of a Destruxin, we looked at changes in gene expression following
      injection of Destruxin A into the fruit fly Drosophila melanogaster. Microarray
      results revealed reduced expression of various antimicrobial peptides that play a
      major role in the humoral immune response of the fly. Flies co-injected with a
      non-lethal dose of Destruxin A and the normally innocuous Gram-negative bacteria
      Escherichia coli, showed increased mortality and an accompanying increase in
      bacterial titers. Mortality due to sepsis was rescued through ectopic activation
      of components in the IMD pathway, one of two signal transduction pathways that
      are responsible for antimicrobial peptide induction. These results demonstrate a
      novel role for Destruxin A in specific suppression of the humoral immune response
      in insects.

PMID- 17227775
TI  - Endotoxin-binding proteins modulate the susceptibility of bacterial endotoxin to
      deacylation by acyloxyacyl hydrolase.
AB  - Acyloxyacyl hydrolase (AOAH) is an eukaryotic lipase that partially deacylates
      and detoxifies Gram-negative bacterial lipopolysaccharides and
      lipooligosaccharides (LPSs or LOSs, endotoxin) within intact cells and
      inflammatory fluids. In cell lysates or as purified enzyme, in contrast,
      detergent is required for AOAH to act on LPS or LOS (Erwin, A. L., and Munford,
      R. S. (1990) J. Biol. Chem. 265, 16444-16449 and Katz, S. S., Weinrauch, Y.,
      Munford, R. S., Elsbach, P., and Weiss, J. (1999) J. Biol. Chem. 274, 36579
      36584). We speculated that the sequential interactions of endotoxin (E) with
      endotoxin-binding proteins (lipopolysaccharide-binding protein (LBP), CD14, and
      MD-2) might produce changes in endotoxin presentation that would allow AOAH
      greater access to its substrate, lipid A. To test this hypothesis, we measured
      the activity of purified AOAH against isolated, metabolically labeled
      meningococcal LOS and Escherichia coli LPS that were presented either as
      aggregates (LOSagg or LPSagg)+/-LBP or as monomeric protein (sCD14 or MD-2)
      endotoxin complexes. Up to 100-fold differences in the efficiency of endotoxin
      deacylation by AOAH were observed, with the following rank order of
      susceptibility to AOAH: E:sCD14>or=endotoxin aggregates (Eagg):LBP (molar ratio
      of E/LBP 100:1)>>Eagg, Eagg:LBP (E/LBP approximately 1, mol/mol), or E:MD-2. AOAH
      treatment of LOS-sCD14 produced partially deacylated LOS still complexed with
      sCD14. The underacylated LOS complexed to sCD14 transferred to MD-2 and thus
      formed a complex capable of preventing TLR4 activation. These findings strongly
      suggest that LBP- and CD14-dependent extraction and transfer of endotoxin
      monomers are accompanied by increased exposure of fatty acyl chains within lipid
      A and that the acyl chains are then sequestered when LOS binds MD-2. The
      susceptibility of the monomeric endotoxin-CD14 complex to AOAH may help constrain
      endotoxin-induced TLR4 activation when endotoxin and membrane CD14 are present in
      excess of MD-2/TLR-4.

PMID- 17227776
TI  - Transcriptional and epigenetic regulation of interleukin-2 gene in activated T
      cells by morphine.
AB  - Chronic morphine inhibits interleukin-2 (IL-2) at both the transcriptional and
      protein synthesis levels. The molecular mechanisms by which morphine decreases IL
      2 are not fully understood. The production of IL-2 is tightly regulated by
      several transcription factors that bind to the IL-2 promoter. Herein, we show
      that chronic morphine treatment results in an increase in cAMP levels with a
      concurrent up-regulation of the cAMP inducible repressor inducible cAMP early
      repressor (ICER)/cAMP response element modulator (CREM) and down-regulation of p
      cAMP-response element-binding protein (CREB) in activated T cells. Furthermore,
      ICER competes for p-CREB binding to the cAMP-responsive elements (CREs) site.
      This leads to the uncoupling of CBP/p300 thereby abrogating IL-2 transcription.
      Overexpression of either antisense CREM or CREB plasmid rescued morphine-induced
      inhibition of IL-2 promoter activity and protein production. In addition, we also
      found that chronic morphine treatment inhibited the acetylation and
      trimethylation of histones and decreased both DNA demethylation and accessibility
      of the IL-2 promoter. These findings suggest that chronic morphine treatment may
      function through both transcriptional and epigenetic mechanisms to inhibit IL-2
      production.

PMID- 17227777
TI  - Predictive factors for incident musculoskeletal disorders in an in-plant
      surveillance program.
AB  - OBJECTIVES: A surveillance program for upper-limb work-related musculoskeletal
      disorders (UWMSD) based on assessment of health and risk factors was implemented
      between 1996 and 2000 in a large shoe factory with overall high levels for
      biomechanical exposure. The study aimed to identify workers with an increased
      risk of UWMSD incidence. METHODS: In 1996, 1997 and 2000, 166 workers filled out
      a questionnaire and underwent a standardized physical examination. Factors from
      the 1996 questionnaire (general, personal and occupational factors) associated
      with UWMSD incidence in 1997 were selected. The predictive role of these
      variables was studied with a logistic model, taking into account also gender and
      age. The performance of a risk score based on this model was studied in 2000,
      using the Wilcoxon test and ROC curves. RESULTS: In 1997, 28 incident cases of
      UWMSD were observed (N = 107, 26.2%). Work pace and prior history of UWMSD were
      the only factors significantly associated with UWMSD incidence in 1997
      (respectively 33% versus 13%, P = 0.02 and 58% versus 22%, P = 0.01).
      Psychological distress (36% versus 21%, P = 0.10), physical fatigue (35% versus
      22%, P = 0.14), repetitiveness (30% versus 18%, P = 0.17) and task precision (33%
      versus 21%, P = 0.16) were also included in the logistic model for 1997 UWMSD
      incidence. Controlling for these variables, prior history of UWMSD remained
      associated with incidence in 1997 (OR = 5.5, 95% CI = 1.4-21.8). In the period
      from 1997 to 2000, 24 incident cases were observed (N = 102, 23.5%). The risk
      score, based on variables from the 1997 model, was significantly higher for
      incident cases (median = 6 in incident cases versus 4.5 for healthy subjects, P =
      0.02). ROC curves indicated that the highest agreement reached 67% for
      sensitivity and 59% for specificity. Among subjects who did not change their task
      (N = 71, 18 incident cases), performance reached 66% for specificity with the
      same sensitivity. CONCLUSION: These results suggest that surveillance programs of
      UWMSD at a company level are possible even with overall high levels for
      biomechanical exposure and should take into account occupational and personal
      factors, including prior history of UWMSD.

PMID- 17227778
TI  - Reconciling national treatment policies and drug regulation in Kenya.

PMID- 17227779
TI  - Socioeconomic position and the risk of gastric and oesophageal cancer in the
      European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).
AB  - OBJECTIVES: To evaluate the association of socioeconomic position with
      adenocarcinoma of the oesophagus and stomach. METHODS: The European Prospective
      Investigation into Cancer and Nutrition (EPIC) cohort comprises about 520 000
      participants mostly aged 35-70 years. Information on diet and lifestyle was
      collected at recruitment. After an average follow-up of 6.5 years, 268 cases with
      adenocarcinoma of the stomach and 56 of the oesophagus were confirmed. We
      examined the effect of socioeconomic position on cancer risk by means of
      educational data and a computed Relative Index of Inequality (RII). In a nested
      case-control study, adjustment for Helicobacter pylori (H. pylori) infection was
      performed. RESULTS: Higher education was significantly associated with a reduced
      risk of gastric cancer [vs lowest level of education, hazard ratio (HR): 0.64,
      95% Confidence intervals (CI): 0.43-0.98]. This effect was more pronounced for
      cancer of the cardia (HR: 0.42, 95% CI: 0.20-0.89) as compared to non-cardia
      gastric cancer (HR: 0.66, 95% CI: 0.36-1.22). Additionally, the inverse
      association of educational level and gastric cancer was stronger for cases with
      intestinal (extreme categories, HR: 0.13, 95% CI: 0.04-0.44) rather than diffuse
      histological subtype (extreme categories, HR: 0.71 95% CI: 0.37-1.40). In the
      nested case-control study, inverse but statistically non-significant associations
      were found after additional adjustment for H. pylori infection [highest vs lowest
      level of education: Odds ratio (OR) 0.53, 95% CI: 0.24-1.18]. Educational level
      was non-significantly, inversely associated with carcinoma of the oesophagus.
      CONCLUSION: A higher socioeconomic position was associated with a reduced risk of
      gastric adenocarcinoma, which was strongest for cardia cancer or intestinal
      histological subtype, suggesting different risk profiles according to educational
      level. These effects appear to be explained only partially by established risk
      factors.

PMID- 17227780
TI  - Vaccination and the risk of childhood acute leukaemia: the ESCALE study (SFCE).
AB  - BACKGROUND: In 2002, a poster alerted the French health authorities to the
      possibility that the risk of childhood leukaemia might be increased by hepatitis
      B vaccination. Elucidating the role of vaccination in the aetiology of childhood
      acute leukaemia (AL) was therefore included in the objectives of an ongoing
      national study. METHODS: The ESCALE study was a French national population-based
      case-control study conducted in France in 2003 and 2004 in order to investigate
      the role of infectious, environmental and genetic factors in four childhood
      neoplastic diseases (leukaemia, lymphoma, neuroblastoma and brain tumour). The
      controls were randomly selected from the French population and age and gender
      frequency matched with the cases. A total of 776 cases of AL (91% of the eligible
      cases) and 1681 controls (71% of the eligible controls) were included. In a
      specific standardized telephone interview, which was the same for both the cases
      and controls, each mother was asked to read out her child's complete vaccination
      record. RESULTS: No association between vaccination and the risk of childhood AL:
      acute lymphoblastic leukaemia or acute myeloblastic leukaemia was observed. No
      relationship between the risk of leukaemia and the type of vaccine, number of
      doses of each vaccine, total number of injections, total number of vaccine doses
      or number of early vaccinations was evidenced. No confounding factor was
      observed. CONCLUSION: The study did not show any evidence of a role of
      vaccination in the aetiology of childhood leukaemia.

PMID- 17227781
TI  - WNT5A--target of CUTL1 and potent modulator of tumor cell migration and invasion
      in pancreatic cancer.
AB  - Previously, we have identified the transcription factor CUTL1 as an important
      mediator of tumor invasion and target of tumor growth factor-beta. Using high
      throughput approaches, we identified several putative downstream effectors of
      CUTL1, among them WNT5A, a secreted member of the Wnt multigene family. The aim
      of this study was to investigate the role of WNT5A as a novel target of CUTL1 in
      pancreatic cancer. CUTL1 and WNT5A were stably over-expressed as well as
      transiently and stably knocked down by RNA interference. Effects on
      proliferation, migration and invasiveness were investigated by thymidine
      incorporation, Boyden chamber experiments and time-lapse microscopy. Expression
      of WNT5A in pancreatic cancer tissues was analyzed by real-time polymerase chain
      reaction (RT-PCR) and immunohistochemistry. We found that CUTL1 transcriptionally
      up-regulated WNT5A on RNA, protein and promoter level. WNT5A significantly
      enhanced migration, proliferation and invasiveness, mediating the pro-invasive
      effects of CUTL1 to a major extent. WNT5A effects were accompanied by a marked
      modulation of marker genes associated with epithelial-mesenchymal transition.
      Using RT-PCR and immunohistochemistry, we found that WNT5A is up-regulated early
      during pancreatic cancerogenesis in pancreatic intraepithelial neoplasias lesions
      and in invasive pancreatic adenocarcinomas, as compared with normal pancreas
      tissues. These data identify WNT5A as important target of CUTL1 and as novel
      mediator of invasiveness and tumor progression in pancreatic cancer.

PMID- 17227782
TI  - Does child labour affect final height?
AB  - BACKGROUND: Although the negative effects of child labour on health are well
      known, the impact of child labour on final height is still controversial. AIMS:
      To assess the effect of child labour on the final height of young adults.
      METHODS: The study included 2063 adults aged 23-25 years from a cohort study of
      all live births (6827) in Ribeirao Preto, Brazil (1978-79). Height was measured
      in centimetres. Information on work, physical activity and smoking was obtained
      retrospectively and the other variables were obtained at cohort baseline. Work
      was classified according to age at first job: <14 (child labour), 14-16 and
      >or=17 years. Analyses were performed separately for males and females. Multiple
      linear regression analysis followed bivariate and stratified analysis. RESULTS:
      The average height for males and females were respectively 176.0 cm [95%
      confidence interval (CI) 175.6-176.4] and 162.7 cm (95% CI 162.3-163.0). Labour
      before the age of 14 years was performed by 20% of males and 12% of females. In
      the bivariate analysis, child labour was statistically associated with final
      height for both males (P < 0.01) and females (P < 0.01). However, the association
      was not maintained after adjusting for confounders. CONCLUSION: We were not able
      to demonstrate significant height differences between those previously employed
      or not employed as a child, other than differences explained by other social and
      biological factors.

PMID- 17227783
TI  - Work-related musculoskeletal disorders in Norway's offshore petroleum industry.
AB  - BACKGROUND: Since 1992, physicians have reported work-related diseases among
      workers in Norway's offshore petroleum industry to the Petroleum Safety
      Authority, as required by law. AIMS: To analyse the number of reported work
      related musculoskeletal disorders and risk factors (occupation and reported
      exposure) from 1992 to 2003. METHODS: Data from the Petroleum Safety Authority's
      registry of work-related diseases were analysed. RESULTS: During the 12 years,
      3131 new work-related musculoskeletal disorders were reported and this was the
      category of work-related disease most frequently reported (47%). The number of
      work-related musculoskeletal disorders varied substantially from year to year.
      Disorders of the upper limb accounted for 53% and back disorders for 20% of all
      work-related musculoskeletal disorders. Lower limb disorders accounted for 16%,
      of which knee disorders dominated (12% of all cases). The dominant occupational
      categories were maintenance work (40%) and catering (21%). Frequently reported
      types of exposure were high physical workload, repetitive work and walking on
      hard surfaces/climbing stairs and ladders. CONCLUSION: Strategies for preventing
      musculoskeletal disorders should be carried out to reduce the burden of high
      physical workload and repetitive work, especially in maintenance work and
      catering. Further research is recommended on the association between walking on
      hard surfaces/climbing stairs and ladders and knee disorders. Reporting routines
      need to be improved to monitor trends over time and to assess the effects of
      interventions.

PMID- 17227784
TI  - Clinical and economic impact of stress echocardiography compared with exercise
      electrocardiography in patients with suspected acute coronary syndrome but
      negative troponin: a prospective randomized controlled study.
AB  - AIMS: Patients attending hospital with suspected acute coronary syndrome (ACS),
      non-diagnostic electrocardiogram (ECG), and negative troponin present a
      diagnostic dilemma for admitting physicians. We sought to determine the clinical
      and economic impact of stress echocardiography (SEcho) when compared with
      exercise ECG (ExECG) in the assessment of these patients. METHODS AND RESULTS:
      Following pre-test assessment by (Thrombolysis in Myocardial Infarction) TIMI
      score, patients were randomized to ExECG (n=218) or SEcho (n=215). Subsequently,
      low-risk patients were discharged; those considered high risk were referred for
      coronary angiography. Patients were followed-up for cardiac events and a cost
      analysis performed. SEcho was superior to ExECG in stratifying patients as low
      risk (77 vs. 33%, respectively, P<0.0001) with no difference in cardiac event
      rate (5 vs. 3%, respectively). SEcho classified fewer patients as intermediate
      risk (3 vs. 39%, respectively, P<0.0001) and fewer patients required further
      tests when compared with ExECG (3 vs. 47%, respectively, P<0.0001). Costs for
      detection of coronary artery disease were significantly less in patients
      undergoing SEcho (pound366.63 vs. pound515.48, P=0.004). CONCLUSION: SEcho is
      superior to ExECG in the risk stratification of patients with suspected ACS but
      negative troponin. SEcho resulted in less diagnostic uncertainty, fewer referrals
      for further investigation, and hence, a significant cost benefit over ExECG.

PMID- 17227785
TI  - Better, (perhaps) cheaper, but is it best?

PMID- 17227786
TI  - A left atrial thrombus too big to embolize.

PMID- 17227787
TI  - Prevalence and prognostic implications of non-sustained ventricular tachycardia
      in ST-segment elevation myocardial infarction after revascularization with either
      fibrinolysis or primary angioplasty.
AB  - AIMS: We compared the prevalence and prognostic implications of non-sustained
      ventricular tachycardia (nsVT) detected early after ST-segment elevation
      myocardial infarction (STEMI) in patients randomized to either fibrinolysis or
      primary angioplasty in the DANAMI-2 trial. METHODS AND RESULTS: Holter recordings
      were available in 1017 patients (fibrinolysis: n=501; primary angioplasty:
      n=516). Primary endpoint was all-cause mortality. The prevalence of nsVT was 8.8%
      in fibrinolysis-treated, and 8.1% in primary angioplasty-treated patients
      (P=0.71). During 4519 patient-years of follow-up (median 4.3 years), 116 patients
      died [fibrinolysis vs. angioplasty: HR=1.1 (95% CI, 0.8-1.6), P=0.47]. In
      univariate analysis, nsVT patients treated with fibrinolysis, had significantly
      higher mortality when compared with those without nsVT (P<0.001). However, after
      adjustment for other relevant prespecified risk factors, the association between
      nsVT and mortality did not remain statistically significant. In patients treated
      with primary angioplasty, nsVT was not associated with mortality in either
      univariate or multivariate analyses. CONCLUSION: Immediate revascularization with
      primary angioplasty for STEMI does not affect the subsequent prevalence of nsVT
      when compared with fibrinolysis. After adjustment for other relevant risk
      factors, the prognostic value of nsVT detected early after STEMI is limited,
      regardless of the chosen reperfusion strategy.

PMID- 17227788
TI  - Adjunctive antiarrhythmic drug therapy in patients with implantable cardioverter
      defibrillators: a systematic review.
AB  - AIMS: To assess the efficacy and safety of adjunctive antiarrhythmic drug therapy
      for preventing implantable cardioverter defibrillator (ICD) therapies. METHODS
      AND RESULTS: We conducted a systematic literature search to identify all
      randomized, controlled trials assessing the efficacy of adjunctive antiarrhythmic
      drug therapy. Trial data were reviewed and extracted independently by two
      investigators in an unblinded, standardized manner. Eight trials including a
      total of 1889 patients were analysed. There was heterogeneity in the type of
      antiarrhythmic used in the treatment arm (amiodarone, sotalol, azimilide, and
      dofetilide) as well as in the control group (five trials compared with placebo
      and three trials compared with beta-blocker). The main outcome, risk of shock
      therapy, was reduced when comparing amiodarone plus beta-blocker with beta
      blocker alone (HR 0.27; 95% CI 0.14-0.52) and when comparing sotalol with placebo
      (HR 0.55; 95% CI 0.4-0.78). The effect was not conclusive when comparing sotalol
      with other beta-blocker (HR 0.61; 95% CI 0.37-1) and azimilide or dofetilide with
      placebo (HR 0.78; 95% CI 0.58-1.04 and HR 0.67; 95% CI 0.43-1.04, respectively).
      Although there were some benefits for secondary outcomes in all antiarrhythmics,
      the magnitude of the benefit was higher with amiodarone. CONCLUSION: Amiodarone
      is the most effective treatment to reduce ICD shock therapies. The benefit of
      other antiarrhythmics is limited to secondary outcomes.

PMID- 17227789
TI  - The common non-synonymous variant G38S of the KCNE1-(minK)-gene is not associated
      to QT interval in Central European Caucasians: results from the KORA study.
AB  - AIMS: The QT interval in the general population is a complex trait with 30-50%
      heritability. QT prolongation is associated with an increased risk of sudden
      death. A recent family-based study found an association between QT interval and
      the common non-synonymous Glycin 38 Serine variant (G38S, rs1805127) of the KCNE1
      gene coding for the minK-potassium channel subunit. We intended to replicate this
      finding in a large population sample of central European Caucasian ancestry as
      part of our ongoing search for genetic variants predisposing to arrhythmias.
      METHODS AND RESULTS: We studied 3966 unrelated individuals from the KORA S4
      population-based study without atrial fibrillation, pacemaker implant, or
      pregnancy. Individuals were genotyped by MALDI-TOF mass spectrometry. We did not
      detect any significant association between the genotypes of the G38S variant and
      the QT interval in the entire population or in any gender. CONCLUSION: Unlike the
      common Lysine 897 Threonine variant of KCNH2 (K897T, rs1805123) the G38S variant
      of KCNE1 does not appear to have a strong modifying effect on QT interval.
      However, we cannot rule out an effect of G38S on QT in other ethnic groups, under
      exercise or medications or on the risk for arrhythmias and sudden death.

PMID- 17227790
TI  - Recombinant human hyaluronidase Hyal-1: insect cells versus Escherichia coli as
      expression system and identification of low molecular weight inhibitors.
AB  - The human hyaluronidase Hyal-1, one of six human hyaluronidase subtypes,
      preferentially degrades hyaluronic acid present in the extracellular matrix of
      somatic tissues. Modulations of Hyal-1 expression have been observed in a number
      of malignant tumors. However, its role in disease progression is discussed
      controversially due to limited information on enzyme properties as well as the
      lack of specific inhibitors. Therefore, we expressed human Hyal-1 in a
      prokaryotic and in an insect cell system to produce larger amounts of the
      purified enzyme. In Escherichia coli, Hyal-1 formed inclusion bodies and was
      refolded in vitro after purification by metal ion affinity chromatography.
      However, the enzyme was produced with extremely low folding yields (0.5%) and
      exhibited a low specific activity (0.1 U/mg). Alternatively, Hyal-1 was secreted
      into the medium of stably transfected Drosophila Schneider-2 (DS-2) cells. After
      several purification steps, highly pure enzyme with a specific activity of 8.6
      U/mg (consistent with the reported activity of human Hyal-1 from plasma) was
      obtained. Both Hyal-1 enzymes showed pH profiles similar to the hyaluronidase of
      human plasma with an activity maximum at pH 3.5-4.0. Deglycosylation of Hyal-1,
      expressed in DS-2 cells, resulted in a decrease in the enzymatic activity
      determined by a colorimetric hyaluronidase activity assay. Purified Hyal-1 from
      DS-2 cells was used for the investigation of the inhibitory activity of new
      ascorbic acid derivatives. Within this series, l-ascorbic acid tridecanoate was
      identified as the most potent inhibitor with an IC(50) of 50 +/- 4 microM
      comparable with glycyrrhizic acid.

PMID- 17227791
TI  - Analysis of news of the Japanese asbestos panic: a supposedly resolved issue that
      turned out to be a time bomb.
AB  - BACKGROUND: Asbestos-linked public health problems were widely reported in Japan,
      in 2005. The objective is to apply text mining with network analysis to
      characterize these problems. METHODS: Text mining with network analysis of
      newspaper headlines including the word 'asbestos' published in 1987 and 2005 was
      conducted. Outcome measures are occurrence of the words and simultaneous
      occurrence of two words in the newspaper headlines. RESULTS: In 36 headlines,
      which contained the word 'asbestos' in 1987, the word 'pollution' (40%) appeared
      most frequently, followed by 'removal' (31%) and 'campaign' (29%). For
      combinations of words, the following occurred most frequently: 'campaign and
      expulsion' (26%) followed by 'removal and campaign' (14%). Of 293 headlines in
      2005, the following words appeared: 'hazard' (31%), 'person' (16%) and 'death'
      (13%). For combinations, the following appeared: 'person and death' (9%).
      Asbestos pollution and removal campaigns were reported in 1987, but the death of
      citizens was reported in 2005. CONCLUSIONS: Text mining with network analysis,
      which presents one of the methods for visualization of text data, suggests the
      following insight. Insufficient steps against asbestos had been taken for 20
      years, which is compatible with the latency period. It has resulted in widespread
      exposure to asbestos and more severe asbestos-related public health problems
      among citizens. This methodology suggests that analyzing text data by this method
      can serve future surveillance and efficient use of epidemiological knowledge.

PMID- 17227792
TI  - The role of spoken and sign languages in the retention of written words by
      prelingually deafened native signers.
AB  - The purpose of this study was to determine the nature and efficiency of the
      strategies used by prelingually deafened native signers for the temporary
      retention of written words with reference to a primary language-coding hypothesis
      (M. A. Shand, 1982). For the gathering of the data, participants were shown lists
      of serially presented written target words that they were asked to recognize
      according to their presentation order from within word pools that contained
      different types of code-specific distracter words. Three performance dimensions
      were examined: (a) false recognition of target words, (b) correct recognition of
      target words, and (c) retention of target word presentation order. Participants
      were prelingually deafened native signers (n=11, average grade level=8.18 [1.17])
      and a hearing control group (n=25, average grade level=9.00 [0.76]). Findings
      from the analysis of the nature of false recognition and the number of correctly
      recognized words show convincingly that formationally similar distracter words
      interfered with the memory performance of the native signers and phonologically
      similar distracter words with that of the hearing control group. It was concluded
      that the participants decoded written words into a code reflecting their primary
      language experience for their temporary retention in working memory.

PMID- 17227793
TI  - Reciprocal regulation of Rac1 and Rho1 in Drosophila circulating immune
      surveillance cells.
AB  - In many cell types it is evident that the small GTPases Rac and Rho regulate each
      other's activities. What is unclear is exactly how this regulation occurs. To
      further elucidate this interaction we examined the activities of Rac1 and Rho1 in
      Drosophila cellular immune surveillance cells. In larvae the cellular immune
      response involves circulating cells (hemocytes) that can be recruited from a
      hematopoietic organ located behind the brain, as well as a sessile population
      found just underneath the larval cuticle. We demonstrate for the first time that
      Rho-kinase activation requires both Rho1 and the Drosophila c-Jun N-terminal
      kinase (Basket). We also show that Rac1, via Basket, regulates Rho1 activity,
      possibly by inhibiting RhoGAPp190. In the reciprocal pathway, co-expression of
      dominant negative Rho-kinase and constitutive active Rho1 induces a Rac1-like
      phenotype. This induction requires the formin Diaphanous. Co-expression of
      dominant negative Rho-kinase and constitutive active Rho1 also induces filopodia
      formation, with Diaphanous enriched at the tips. The Rac1-like phenotypes, and
      filopodia formation, could be blocked by co-expression of dominant negative Rac1.
      Finally, though dominant negative Rac1 is able to block filopodia formation in
      the overexpression experiments, only Rac2 is necessary for filopodia formed by
      hemocytes after parasitization.

PMID- 17227794
TI  - Filamin links cell shape and cytoskeletal structure to Rho regulation by
      controlling accumulation of p190RhoGAP in lipid rafts.
AB  - Cytoskeleton-dependent changes in the activity of the small GTPase Rho mediate
      the effects of cell shape on cell function; however, little is known about how
      cell spreading and related distortion of the cytoskeleton regulate Rho activity.
      Here we show that rearrangements of the actin cytoskeleton associated with early
      phases of cell spreading in human microvascular endothelial (HMVE) cells suppress
      Rho activity by promoting accumulation of p190RhoGAP in lipid rafts where it
      exerts its Rho inhibitory activity. p190RhoGAP is excluded from lipid rafts and
      Rho activity increases when cell rounding is induced or the actin cytoskeleton is
      disrupted, and p190RhoGAP knockdown using siRNA prevents Rho inactivation by cell
      spreading. Importantly, cell rounding fails to prevent accumulation of p190RhoGAP
      in lipid rafts and to increase Rho activity in cells that lack the cytoskeletal
      protein filamin. Moreover, filamin is degraded in spread cells and cells that
      express a calpain-resistant form of filamin exhibit high Rho activity even when
      spread. Filamin may therefore represent the missing link that connects
      cytoskeleton-dependent changes of cell shape to Rho inactivation during the
      earliest phases of cell spreading by virtue of its ability to promote
      accumulation of p190RhoGAP in lipid rafts.

PMID- 17227795
TI  - Functional genomics in Trypanosoma brucei identifies evolutionarily conserved
      components of motile flagella.
AB  - Cilia and flagella are highly conserved, complex organelles involved in a variety
      of important functions. Flagella are required for motility of several human
      pathogens and ciliary defects lead to a variety of fatal and debilitating human
      diseases. Many of the major structural components of cilia and flagella are
      known, but little is known about regulation of flagellar beat. Trypanosoma
      brucei, the causative agent of African sleeping sickness, provides an excellent
      model for studying flagellar motility. We have used comparative genomics to
      identify a core group of 50 genes unique to organisms with motile flagella. These
      genes, referred to as T. brucei components of motile flagella (TbCMF) include 30
      novel genes, and human homologues of many of the TbCMF genes map to loci
      associated with human ciliary diseases. To characterize TbCMF protein function we
      used RNA interference to target 41 TbCMF genes. Sedimentation assays and direct
      observation demonstrated clear motility defects in a majority of these knockdown
      mutants. Epitope tagging, fluorescence localization and biochemical fractionation
      demonstrated flagellar localization for several TbCMF proteins. Finally,
      ultrastructural analysis identified a family of novel TbCMF proteins that
      function to maintain connections between outer doublet microtubules, suggesting
      that they are the first identified components of nexin links. Overall, our
      results provide insights into the workings of the eukaryotic flagellum, identify
      several novel human disease gene candidates, reveal unique aspects of the
      trypanosome flagellum and underscore the value of T. brucei as an experimental
      system for studying flagellar biology.

PMID- 17227796
TI  - Wnt/beta-catenin mediates radiation resistance of Sca1+ progenitors in an
      immortalized mammary gland cell line.
AB  - The COMMA-Dbeta-geo cell line has been shown to contain a permanent subpopulation
      of progenitor cells that are enriched in outgrowth potential. Using the COMMA
      Dbeta-geo cell line as a model, we sought to study the radioresistance of mammary
      progenitor cells. Using the putative progenitor cell marker stem cell antigen 1
      (Sca1), we were able to isolate a discrete subpopulation of Sca1(+) multipotent
      cells from the immortalized COMMA-Dbeta-geo murine mammary cell line. At a
      clinically relevant dose, the Sca1(+) cells were resistant to radiation (2 Gy).
      Sca1(+) cells contained fewer gamma-H2AX(+) DNA damage foci following
      irradiation, displayed higher levels of endogenous beta-catenin, and selectively
      upregulated survivin after radiation. Expression of active beta-catenin enhanced
      self-renewal preferentially in the Sca1(+) cells, whereas suppressing beta
      catenin with a dominant negative, beta-engrailed, decreased self-renewal of the
      Sca1(+) cells. Understanding the radioresistance of progenitor cells may be an
      important factor in improving the treatment of cancer. The COMMA-Dbeta-geo cell
      line may provide a useful model to study the signaling pathways that control
      mammary progenitor cell regulation.

PMID- 17227797
TI  - Pancreatic stellate cells are an important source of MMP-2 in human pancreatic
      cancer and accelerate tumor progression in a murine xenograft model and CAM
      assay.
AB  - The effect of the characteristic desmoplastic reaction of pancreatic cancer on
      tumor progression is largely unknown. We investigated whether pancreatic stellate
      cells, which are responsible for the desmoplastic reaction, support tumor
      progression. Immunohistology revealed that matrix metalloproteinase-2 (MMP-2),
      which is suggested to promote pancreatic cancer progression, is present in
      stellate cells adjacent to cancer cells. In vitro, stellate cells exhibited a
      much higher basal expression of MMP-2 compared with cancer cells. Panc1-,
      MiaPaCa2- and SW850-conditioned media stimulated MMP-2 release of stellate cells
      as detected by zymography. Cancer cells expressed and released basigin [BSG,
      extracellular matrix metalloproteinase inducer (EMMPRIN), CD147], a glycoprotein
      that is known to stimulate MMP-2 in mesenchymal cells, as detected by
      immunostaining, western blot and reverse transcription-polymerase chain reaction.
      Tumor cell-conditioned medium and BSG purified by affinity chromatography from
      supernatants of cancer cells, but not supernatants depleted from BSG, stimulated
      expression of MMP-1 and MMP-2 of stellate cells as demonstrated by western blot
      and zymography. Moreover, the interaction of stellate cells and cancer cells
      promoted the invasiveness of Panc-1 cells in the chorioallantoic membrane assay
      and increased the weight of tumors induced by all carcinoma cell lines in nude
      mice by 2.1-3.7-fold. Our findings support the assumption that the interaction of
      stellate cells and cancer cells promotes progression of pancreatic cancer.

PMID- 17227798
TI  - Patient perception of the Human Fertilisation and Embryology Authority.

PMID- 17227799
TI  - A woman's choice? The gendered risks of voluntary euthanasia and physician
      assisted suicide.

PMID- 17227800
TI  - Pituitary-gonadal function in adolescent males born appropriate or small for
      gestational age with or without intrauterine growth restriction.
AB  - CONTEXT: Being born small for gestational age (SGA) is suggested to influence
      female pituitary-gonadal axis, but only a few studies have focused on male
      pituitary-gonadal function. OBJECTIVE: Our objective was to evaluate the
      influence of fetal growth rate on male reproductive function. DESIGN: We
      conducted a follow-up study of a prospective study with data on third trimester
      fetal growth velocity and birth weight. SETTING: The study was conducted at
      Copenhagen University Hospital. PARTICIPANTS: Fifty-two healthy adolescent males
      participated. They were divided into those born appropriate for gestational age
      (AGA) and SGA, with or without intrauterine growth restriction. MAIN OUTCOME
      MEASURES: Pubertal stage, testicular size, and reproductive hormones were
      determined. Overnight 20-min LH and FSH profiles and overnight urine LH and FSH
      were determined in an additional study (n=30). RESULTS: No significant
      differences were found in testosterone levels (19.2 vs. 18.9 nmol/liter), inhibin
      B levels (186.5 vs. 188.0 pg/ml), or LH/testosterone ratio (0.15 vs. 0.18)
      between AGA and SGA, respectively. No significant differences in overnight
      secretory patterns of gonadotropins or testicular size and morphology were
      determined by ultrasonography between AGA and SGA. Fetal growth velocity did not
      influence any of the reproductive hormone levels. Overnight urinary LH and FSH
      excretion correlated statistically significantly with overnight LH (r=0.50;
      P=0.02) and FSH (r=0.44; P=0.04) secretion, respectively. CONCLUSION: Poor third
      trimester growth and/or low birth weight had no effect on subsequent male
      reproductive hormones. Contrasting a previous study, we found no difference in
      testosterone or inhibin B levels between SGA and AGA, suggesting that testicular
      function was not impaired in adolescent males born after compromised fetal
      growth.

PMID- 17227801
TI  - Annual zoledronate increases bone density in highly active antiretroviral therapy
      treated human immunodeficiency virus-infected men: a randomized controlled trial.
AB  - CONTEXT: Recent studies have reported low bone mineral density (BMD) in HIV
      infected patients. Annual iv administration of 4 mg zoledronate has been shown to
      increase BMD and suppress bone turnover in postmenopausal women. OBJECTIVE: The
      objective of the study was to determine whether annual administration of 4 mg
      zoledronate will increase BMD in HIV-infected men receiving highly active
      antiretroviral therapy. DESIGN AND SETTING: A 2-yr randomized placebo-controlled
      trial was conducted in a clinical research center. PARTICIPANTS: A total of 43
      HIV-infected men were treated with highly active antiretroviral therapy for at
      least 3 months, with BMD T score less than -0.5. INTERVENTION: Participants
      received annual iv administration of 4 mg zoledronate or placebo. All
      participants took 400 mg/d calcium and 1.25 mg/month vitamin D. MEASUREMENTS: BMD
      at the lumbar spine, total hip and total body, and bone turnover markers were
      measured. RESULTS: At the lumbar spine, BMD increased by 8.9% over 2 yr in the
      zoledronate group compared with an increase of 2.6% in the control group
      (P<0.001). At the total hip, BMD increased by 3.8% over 2 yr in the zoledronate
      group compared with a decrease of 0.8% in the control group (P<0.001). At the
      total body, BMD increased by 2.3% over 2 yr compared with a decrease of 0.5% in
      the control group (P<0.001). Urine N-telopeptide decreased by 60% at 3 months in
      the zoledronate group and thereafter remained stable. CONCLUSIONS: Annual
      administration of zoledronate is a potent and effective therapy for the
      prevention or treatment of bone loss in HIV-infected men. The current data
      provide the first trial evidence of the BMD effects of annual zoledronate beyond
      1 yr in any population, as well as being the first reported trial in men.

PMID- 17227802
TI  - Alendronate prevents bone loss in patients with acute spinal cord injury: a
      randomized, double-blind, placebo-controlled study.
AB  - CONTEXT: Patients who sustain an acute spinal cord injury (SCI) experience rapid
      dramatic reductions in bone mineral density (BMD), especially marked in
      sublesional areas and sometimes leading to hypercalcemia and hypercalciuria, as
      well as increased fracture risk. OBJECTIVE: In this prospective, double-blind,
      randomized, placebo-controlled study, we evaluated the hypothesis that oral
      alendronate administration would preserve BMD when administered soon after acute
      SCI. PATIENTS AND INTERVENTION: Thirty-one patients with acute SCI were randomly
      allocated to receive oral alendronate 70 mg/wk or placebo, within 10 d of acute
      SCI, for 12 months. MAIN OUTCOME MEASUREMENTS: At entry and at 3, 6, 12, and 18
      months, total body bone density, lumbar and hip BMD, ultrasound of the calcaneus,
      24-h urinary calcium, and serum C-telopeptide (betaCTX) were measured. RESULTS:
      At study entry, patients in the two groups were well matched for age, gender,
      severity of neurological deficit, BMD, urinary calcium, and betaCTX. BMD indices
      declined steadily in the placebo group, and this effect was attenuated
      significantly by alendronate. After 12 months, there was a 5.3% difference
      (P<0.001) in total body BMD and a 17.6% difference (P<0.001) in the total hip BMD
      between the two groups. Alendronate compared with placebo induced significant
      (P<0.001) reductions in urinary calcium excretion and serum betaCTX. No treatment
      related side effects were noted. CONCLUSIONS: We conclude that alendronate
      therapy, 70 mg/wk, initiated soon after acute SCI, prevents bone loss and is not
      associated with side effects.

PMID- 17227803
TI  - Malignant paragangliomas associated with mutations in the succinate dehydrogenase
      D gene.
AB  - INTRODUCTION: Malignant paragangliomas have been well described in carriers of
      mutations of the succinate dehydrogenase B (SDHB) gene, but have rarely been
      associated with mutations in the succinate dehydrogenase D (SDHD) gene. AIM: The
      aim of the study was to report the different clinical expression patterns of
      malignant paragangliomas in five patients with SDHD (D92Y) mutations observed in
      approximately 200 SDHD (D92Y) mutation carriers followed in our institution.
      RESULTS: Metastasis and/or local tumor invasion was documented 0 (n=2), 1, 18,
      and 30 yr after the initial diagnosis of paraganglioma. Malignancy was proven by
      paraganglioma bone metastases (n=2), intrathoracic paraganglioma with lymph node
      metastases, locally invasive head-and-neck paraganglioma with destruction of the
      petrosal bone, and locally invasive paraganglioma of the bladder with lymph node
      metastases. Four of the five patients developed catecholamine excess during
      follow-up due to intraadrenal paraganglioma (pheochromocytoma) (n=1), extra
      adrenal paraganglioma (n=2), and presumed subclinical disease (n=1). CONCLUSION:
      SDHD mutations (D92Y) are associated with malignant paragangliomas and
      catecholamine excess with remarkable interindividual variations despite the same
      mutation. We estimate that the prevalence of malignancy in carriers of D92Y
      mutations is at least 2.5%.

PMID- 17227804
TI  - Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron emission tomography as a
      tool to localize an insulinoma or beta-cell hyperplasia in adult patients.
AB  - CONTEXT AND OBJECTIVE: Fluorine-18-L-dihydroxyphenylalanine (18F-DOPA) positron
      emission tomography (PET) is a promising method in localizing neuroendocrine
      tumors. Recently, it has been shown to differentiate focal forms of congenital
      hyperinsulinism of infancy. The current study was set up to determine the
      potential of 18F-DOPA PET in identifying the insulin-secreting tumors or beta
      cell hyperplasia of the pancreas in adults. PATIENTS AND METHODS: We
      prospectively studied 10 patients with confirmed hyperinsulinemic hypoglycemia
      and presumed insulin-secreting tumor using 18F-DOPA PET. Anatomical imaging was
      performed with computed tomography (CT) and magnetic resonance imaging (MRI). All
      patients were operated on, and histological verification was available in each
      case. Semiquantitative PET findings in the pancreas using standardized uptake
      values were compared to standardized uptake values of seven consecutive patients
      with nonpancreatic neuroendocrine tumors. RESULTS: By visual inspection of 18F
      DOPA PET images, it was possible in nine of 10 patients to localize the
      pancreatic lesion, subsequently confirmed by histological analysis. 18F-DOPA
      uptake was enhanced in six of seven solid insulinomas and in the malignant
      insulinoma and its hepatic metastasis. Two patients with beta-cell hyperplasia
      showed increased focal uptake of 18F-DOPA in the affected areas. As compared to
      CT or MRI, 18F-DOPA PET was more sensitive in localizing diseased pancreatic
      tissue. CONCLUSION: 18F-DOPA PET was useful in most patients with insulinoma and
      negative CT, MRI, and ultrasound results. In agreement with previous findings in
      infants, preoperative 18F-DOPA imaging seems to be a method of choice for the
      detection of beta-cell hyperplasia in adults. It should be considered for the
      detection of insulinoma or beta-cell hyperplasia in patients with confirmed
      hyperinsulinemic hypoglycemias when other diagnostic work-up is negative.

PMID- 17227805
TI  - Protein metabolism in acromegaly: differential effects of short- and long-term
      treatment.
AB  - CONTEXT: GH acutely increases body protein by stimulating protein synthesis and
      reducing protein oxidation. OBJECTIVE: The objective of the study was to
      determine whether these changes in protein metabolism are sustained in long-term
      GH excess and reversed by correction. DESIGN: We conducted a cross-sectional
      study in 16 acromegalic and 18 normal subjects and a longitudinal study in which
      acromegalic subjects were studied before and after short-term (n=8) or long-term
      (n=10) treatment. SETTING: The study was conducted at a clinical research center.
      MAIN OUTCOME MEASURES: Whole-body rates of leucine appearance (leucine Ra; an
      index of protein breakdown), leucine oxidation, and nonoxidative leucine disposal
      (NOLD; an index of protein synthesis) estimated using infusion of 1-[13C] leucine
      were measured. RESULTS: Leucine Ra and NOLD were greater (P<0.01) in acromegalic
      compared with normal subjects, whereas leucine oxidation did not differ. Leucine
      oxidation increased significantly (P<0.05) after short-term treatment but
      returned to baseline after long-term treatment. Both leucine Ra and NOLD
      decreased significantly (P<0.05) after short- and long-term treatment. Adjustment
      for body composition did not affect results. CONCLUSIONS: In acromegalic
      subjects, protein breakdown and synthesis are increased, whereas protein
      oxidation does not differ from normal subjects. Protein oxidation increases
      transiently, whereas protein breakdown and synthesis are stably reduced after
      treatment. Because protein oxidation represents irreversible loss, we conclude
      that the normal state of protein oxidation found in acromegaly and after long
      term treatment represents metabolic adaptation, which maintains protein mass at a
      steady state after stable changes in GH status.

PMID- 17227806
TI  - High plasma level of remnant-like particles cholesterol in familial combined
      hyperlipidemia.
AB  - CONTEXT: The traditional lipid and lipoprotein levels in patients with familial
      combined hyperlipidemia (FCH) are relatively mildly elevated and do not fully
      explain the increased risk of cardiovascular disease (CVD). In other populations,
      high remnant-like particles cholesterol (RLP-C) levels are an independent risk
      factor for CVD. OBJECTIVE: The objective of the study was to investigate whether
      plasma RLP-C concentrations are elevated in patients with FCH and contribute to
      the increased prevalence of CVD. DESIGN, SETTING, PARTICIPANTS: In this cross
      sectional study, we studied RLP-C levels in 37 FCH families comprising 582
      subjects, of whom 134 subjects were diagnosed FCH based on total cholesterol,
      triglyceride, and apolipoprotein-B levels. Plasma RLP-C concentrations were
      determined using an immune-separation technique. RESULTS: For both men and women,
      the mean plasma RLP-C concentration (mmol/liter) was 2-fold elevated in FCH
      patients [0.59 (0.54-0.66) and 0.40 (0.37-0.43), respectively] compared with both
      normolipidemic relatives [0.27 (0.26-0.29) in male and 0.22 (0.21-0.23) in
      female, all P<0.000]; and spouses [0.27 (0.23-0.31) in male and 0.24 (0.21-0.27)
      in female, all P<0.000]. Plasma RLP-C levels above the 90th percentile predicted
      prevalent CVD, independently of nonlipid cardiovascular risk factors [odds ratio
      2.18 (1.02-4.66)] and triglyceride levels [odds ratio 2.35 (1.15-4.83)]. However,
      in both FCH patients and controls, RLP-C did not provide additional information
      about prevalent CVD over and above non-high-density lipoprotein cholesterol
      levels. CONCLUSIONS: Patients with FCH have 2-fold elevated plasma RLP-C levels,
      which add to the atherogenic lipid profile and contribute to the increased risk
      for CVD. However, for clinical practice, non-high-density lipoprotein cholesterol
      is the best predictor of prevalent CVD.

PMID- 17227808
TI  - Is omitting post urinary-tract-infection renal ultrasound safe after normal
      antenatal ultrasound? An observational study.
AB  - BACKGROUND: Guidelines recommend obtaining a renal ultrasonogram (RUS) for young
      children after a first urinary tract infection (UTI). OBJECTIVE: The aim of the
      current study was to assess the concordance of prenatal and post-UTI RUS findings
      in children with a first simple UTI. METHODS: This was a prospective study and
      included all children aged 5 years or younger who were hospitalised with a first
      simple UTI (determined as clinical response and normalisation of temperature
      within 48 h on initiation of antibacterial therapy with no complications). Data
      were collected from each child regarding the results of prenatal and post-UTI
      RUS. RESULTS: Overall, 250 children were included in the study and the results of
      late-pregnancy and post-UTI RUS were available for 84% (n = 209). Complete
      concordance between the two RUS was demonstrated in 96% (n = 201). The predictive
      value of normal antenatal to normal post-UTI RUS was 96% (95% CI: 93% to 99%).
      These results include four children with mild transient pelvic dilatation. In
      eight children in whom renal anomalies were demonstrated only in post-UTI RUS,
      the influence of these anomalies on the children's management was negligible.
      CONCLUSIONS: Prenatal-RUS have been performed in most children <5 years old
      hospitalised with a first simple UTI. Concordance with post-infection tests is
      very high. Findings which appear only in post-infectious RUS usually have
      negligible effects on children's management. Thus, in such children with normal
      antenatal RUS omitting post-UTI RUS could be considered.

PMID- 17227807
TI  - Epidemiology of neonatal group B streptococcal disease in the Netherlands before
      and after introduction of guidelines for prevention.
AB  - OBJECTIVES: (1) To describe the epidemiology of neonatal group B streptococcal
      (GBS) disease over five years (1997-2001) in the Netherlands, stratified for
      proven and probable sepsis and for very early (<12 h), late early (12 h - <7
      days) and late (7-90 days) onset sepsis. (2) To evaluate the effect of the
      introduction in January 1999 of guidelines for prevention of early onset GBS
      disease based on risk factors. METHODS: Data on cases were collected in
      collaboration with the Dutch Paediatric Surveillance Unit and corrected for under
      reporting by the capture-recapture technique. RESULTS: Total incidence of proven
      very early onset, late early onset and late onset GBS sepsis was 0.32, 0.11 and
      0.14 per 1000 live births, respectively, and of probable very early onset, late
      early onset and late onset GBS sepsis was 1.10, 0.18 and 0.02 per 1000 live
      births, respectively. Maternal risk factors were absent in 46% of the proven
      early onset cases. Considerably more infants with proven GBS sepsis were boys.
      64% of the infants with proven very early onset GBS sepsis were first born
      compared with 47% in the general population. After the introduction of guidelines
      the incidence of proven early onset sepsis decreased considerably from 0.54 per
      1000 live births in 1997-8 to 0.36 per 1000 live births in 1999-2001. However,
      there was no decrease in the incidence of meningitis and the case fatality rate
      in the first week of life. The incidence of late onset sepsis also remained
      unchanged. CONCLUSION: After the introduction prevention guidelines based on risk
      factors there has been a limited decrease in the incidence of proven early onset
      GBS sepsis in the Netherlands. This study therefore recommends changing the Dutch
      GBS prevention guidelines.

PMID- 17227809
TI  - Effect of oral administration of dydrogestrone versus vaginal administration of
      natural micronized progesterone on the secretory transformation of endometrium
      and luteal endocrine profile in patients with premature ovarian failure: a proof
      of concept.
AB  - BACKGROUND: We aimed to explore the endometrial histology and endocrine profiles
      on day 21 of an artificial cycle in patients with premature ovarian failure (POF)
      treated with oral dydrogesterone (DG) or vaginal micronized progesterone.
      METHODS: The study was designed as a prospective pilot study at an academic
      reproductive medicine unit. Six POF patients were included in the study. After
      estrogen endometrial priming, patients were randomized to receive DG or
      progesterone in two subsequent cycles. The main outcome measure was the
      endometrial histology and the endocrine profiles on day 21 of the cycle. RESULTS:
      Development of endometrial glands corresponded to an early secretory phase in
      five out of six cases supplemented with DG (out-phase). In contrast, five out of
      six cases treated with micronized progesterone showed an endometrium
      corresponding to a mid-luteal phase (in-phase) (P = 0.021 versus DG). There was a
      significant difference in the mean progesterone value [8.6 versus 0.3 microg l(
      1) (P = 0.013)], the mean LH value [12.9 versus 22.5 IU l(-1) (P = 0.049)] and
      the mean FSH value [13.0 versus 23.9 IU l(-1) (P = 0.047)] between the
      progesterone and DG group, respectively, on day 21 of the cycle. CONCLUSIONS:
      After estrogen endometrial priming in POF patients, exogenous vaginal micronized
      progesterone is more effective than oral DG in creating an 'in-phase' secretory
      endometrium and induces significantly higher progesterone and lower LH and FSH
      serum concentrations on day 21 of the cycle.

PMID- 17227810
TI  - Age-related role of ambulatory electrocardiographic monitoring in risk
      stratification of patients with complete congenital atrioventricular block.
AB  - AIMS: The aim of the paper was to assess the importance of 24 h
      electrocardiographic Holter monitoring in determining predictive factors for
      Adams-Stokes (AS) attacks and heart failure (HF) in children and adolescents with
      complete congenital atrioventricular block (CCAVB). METHODS AND RESULTS: Forty
      five patients were divided into two groups according to the presence of AS
      attacks and HF and six age-related subgroups. The following parameters of 24 h
      electrocardiographic Holter monitoring were analysed: (i) minimum heart rate
      (HR), (ii) maximum HR, (iii) average HR, (iv) daytime HR (v) rhythm and
      conduction disturbance. Adams-Stokes attacks and HF occurred in 10 and 8
      patients, respectively (40%). Five of six neonates with HF had maximum HR < 74
      bpm and daytime HR < 58 bpm. Maximum HR below 68 bpm and daytime HR below 52 bpm
      were recorded in all the children up to 8 years of age with AS attacks and HF and
      only in 3 of 14 asymptomatic patients. All the patients above 8 years of age with
      AS attacks had maximum HR below 62 bpm. Of 6 patients with daytime HR < 50 bpm AS
      attacks were present in two. Episodes of marked ventricular slowing during sleep
      were registered in 4 of 10 (40%) patients and in 3 of 27 (11%) symptomless
      patients. CONCLUSION: Risk factors for development of AS attacks and HF in
      patients with CCAVB include: (i) maximum HR < 74 bpm in neonates, <68 bpm up to
      the age of 8 and <62 bpm at ages above 8, (ii) daytime HR <58 bpm in neonates and
      < 52 bpm till the age of 8, and (iiii) abrupt pauses in ventricular rate that are
      at least twice the basic cycle length after the neonatal period.

PMID- 17227811
TI  - Medium-term follow-up and modes of failure following epicardial pacemaker
      implantation in young children.
AB  - AIMS: Young children suffering from congenital or post-operative AV-block require
      life-long pacemaker stimulation. Due to the anatomical prerequisites initially
      epicardial electrodes are implanted and the generator is placed in the upper
      abdominal wall. The following study investigated modes of failure leading to
      reoperation in this group of technically challenging patients. METHODS AND
      RESULTS: Between October 2000 and May 2005, a total of 21 infants (age 3 days to
      5 years) underwent pacemaker implantation using a subxyphoidal incision for
      newborns (and a partial lower or complete median sternotomy for older children).
      Nine patients had previous cardiac surgery for complex congenital defects. The
      remaining 12 young children suffered from congenital AV-Block (CAVB). Twenty-one
      bipolar epicardial electrodes (Medtronic Capsure epi) were fixed to the right
      ventricle, 15 had additional implantation of a bipolar atrial lead. The pacemaker
      generator (Medtronic Kappa 701) was implanted into the right upper abdominal
      wall. Indications for revision were recorded. No mortality was observed; pacing
      and sensing parameters remained stable up to a 5-year follow-up. A total of four
      reoperations occurred. Three of the four revisions were caused by ventricular
      electrode fracture. At revision, two electrodes were broken at the crossing
      between the pericardial cavity and the abdominal wall, one bipolar lead at the Y
      division into the two tip electrodes. One reoperation was due to a pacemaker
      recall. All revisions were performed without complications. CONCLUSION: In our
      institute epicardial pacing in young children was associated with a satisfactory
      clinical outcome, but also a significant number of failures leading to
      reoperation, mainly due to electrode fracture caused by the muscular activity of
      this patient group. Reoperations were performed at a low risk.

PMID- 17227813
TI  - Natriuretic peptides in patients with atrial fibrillation and advanced chronic
      heart failure: determinants and prognostic value of (NT-)ANP and (NT-pro) BNP.

PMID- 17227814
TI  - Superiority of the Lyon schuss view over the standing anteroposterior view for
      detecting joint space narrowing, especially in the lateral tibiofemoral
      compartment, in early knee osteoarthritis.
AB  - OBJECTIVE: To evaluate the validity of using the conventional anteroposterior
      (AP) radiograph of the knee in order to identify joint space narrowing (JSN) at
      an early stage of osteoarthritis (OA). METHODS: Grading of JSN using a 0-5 score
      and quantitative measurement of joint space width (JSW) of the medial and lateral
      compartments of the tibiofemoral joint in AP and fluoroscopically assisted
      posteroanterior Lyon schuss (LS) radiographs of 202 patients with knee OA.
      RESULTS: Knees without definite JSN (score <2) were twice as common in AP than in
      LS radiographs (36.1% vs 18.8%). The number of knees showing definite medial JSN
      was identical in both views but four knees showing a medial OA in AP view were
      classified differently in the LS radiographs (three bicompartmental OA and one
      lateral OA). The frequency of lateral JSN was approximately twice as great in the
      LS view as in the AP view. JSN score was significantly higher (p<0.001) and JSW
      was significantly smaller (p<0.01) in the LS view than in the AP view. In knees
      with definite JSN, JSW of the compartment with no narrowing was significantly
      (p<0.04) larger than in knees that did not exhibit definite JSN. Medial JSW and
      lateral JSW were inversely correlated (p<0.001). CONCLUSIONS: The standing AP
      radiograph performed poorly in identifying both the location of JSN in patients
      with early tibiofemoral OA (especially, lateral OA) and the severity of JSN. The
      LS radiographs are preferable to standing AP views for the selection of patients
      for therapeutic trials of structure-modifying OA drugs.

PMID- 17227816
TI  - Increased cystatin C expression in the pre-eclamptic placenta.
AB  - Trophoblast invasion is regulated by proteinases and their inhibitors. Cystatin C
      inhibits cysteine proteinases. The serum concentration of cystatin C is increased
      in late pregnancy and pre-eclampsia. We aimed to investigate whether the
      expression of cystatin C is increased in the pre-eclamptic placenta and to
      investigate the expression pattern of cystatin C mRNA and protein in placental
      tissue. Tissue samples from the central part of the placenta from 13 normal and
      22 pre-eclamptic pregnancies were included. We used real-time polymerase chain
      reaction (RT-PCR) and in situ hybridization for mRNA expression analysis and
      immunohistochemistry and Western blotting for protein expression analysis. RT-PCR
      showed a significantly higher expression of cystatin C mRNA in pre-eclampsia than
      in normal pregnancy, with the highest expression in cases with severe pre
      eclampsia. In situ hybridization revealed a distinct pattern of high expression
      in the extravillous trophoblast cells of the basal plate and low expression in
      the syncytiotrophoblast covering villi. The cystatin C protein distribution
      matched the mRNA expression pattern. Western blot analysis revealed an increased
      protein expression in cases with severe pre-eclampsia and confirmed the presence
      of cystatin C in amniotic fluid samples. The high expression of cystatin C mRNA
      in the extravillous trophoblast cells of the basal plate suggests a role for
      cystatin C in the regulation of proteases in placentation. Placental expression
      and secretion of cystatin C could contribute to the elevated maternal plasma
      levels seen in pre-eclampsia.

PMID- 17227815
TI  - Involvement of nuclear factor-kB activation through RhoA/Rho-kinase pathway in
      LPS-induced IL-8 production in human cervical stromal cells.
AB  - Interleukin-8 (IL-8) is a chemokine that recruits and activates neutrophils in
      stromal tissue and plays an essential role in cervical ripening. Nuclear factor
      kB (NF-kB) is known to be important for the up-regulation of IL-8 gene
      expression. We examined the molecular mechanisms responsible for NF-kB activation
      in IL-8 production in cervical stromal cells. Lipopolysaccharide (LPS) and IL
      1beta stimulated IL-8 production by cervical stromal cells in a dose-dependent
      manner. Pretreatment of cervical stromal cells with inhibitors of RhoA (C3
      transferase exoenzyme), Rho-kinase (Y-27632) or NF-kB (BAY11-7082) effectively
      blocked LPS-induced IL-8 release. In contrast, IL-1beta-induced IL-8 production
      was significantly blocked by BAY11-7082, but not by C3 transferase exoenzyme or Y
      27632. Pull-down assays showed that LPS activated RhoA, but IL-1beta caused only
      a lower level of activation. Transfection of the cervical stromal cells with RhoA
      small interfering RNA (siRNA) inhibited LPS-stimulated IL-8 production, whereas
      IL-1beta-induced IL-8 production was not significantly inhibited by knockdown of
      RhoA with siRNA. Using an NF-kB transcription reporter vector, luciferase assays
      demonstrated that incubation with LPS or IL-1beta induced the activation of NF-kB
      in cervical stromal cells. Activation of NF-kB by LPS was inhibited by treatment
      with C3 exoenzyme, Y-27632 or RhoA siRNA. However, inhibition of the RhoA/Rho
      kinase pathway did not attenuate the activation of NF-kB by IL-1beta. These
      results suggest that LPS-induced IL-8 production is accompanied by enhanced NF-kB
      activation through the RhoA/Rho-kinase pathway in human cervical cells.

PMID- 17227817
TI  - Predictive value of IL-18 and SC5b-9 for neurocognitive dysfunction after
      cardiopulmonary bypass.
AB  - BACKGROUND: Neurological injury after cardiopulmonary bypass (CPB) continues to
      be a major problem after cardiac surgery. The aim of this study was to
      investigate the predictive value of Interleukin-18 (IL-18) and SC5b-9 as
      biochemical markers of neurocognitive dysfunction after cardiac surgery. METHODS:
      A total of 30 patients undergoing elective cardiac surgery using CPB were
      recruited. Blood samples were obtained for IL-18 and SC5b-9 concentrations before
      induction, 24, 48, 72, 96 and 120 h post-CPB and 6 weeks after operation. In
      addition, patients underwent a standard battery of neuropsychometric tests before
      operation and at day 5 and 6 weeks after operation. RESULTS: Serum concentration
      of IL-18, but not SC5b-9, was significantly different between patients with and
      without neurocognitive dysfunction; serum IL-18 concentration significantly
      increased in patients with neurocognitive dysfunction (P = 0.018). Neurological
      outcome was significantly dependent on peak difference in IL-18 concentration at
      day 5 (P = 0.033), but not on peak difference in SC5b-9 concentration (P = 0.16).
      Eight patients had neurocognitive dysfunction at day 5 and three had
      neurocognitive dysfunction at 6 weeks. In a very small number of patients, no
      significant association was demonstrated between IL-18 or SC5b-9 concentrations
      and neurocognitive dysfunction at 6 weeks. CONCLUSIONS: IL-18 has the potential
      as a useful marker of neurological dysfunction, requiring further investigation.

PMID- 17227818
TI  - Intrathecal betamethasone for cancer pain in the lower half of the body: a study
      of its analgesic efficacy and safety.
AB  - BACKGROUND: Sufficient analgesia for cancer pain is sometimes difficult to
      achieve with conventional treatments. We aimed at investigating the analgesic
      efficacy and safety of intrathecal betamethasone in patients with uncontrollable
      cancer pain. METHODS: Betamethasone 1 mg mixed with saline was injected into the
      lumbar intrathecal space once a week in 10 patients with persistent cancer pain
      in the lower half of the body. During the 4-week study period, the analgesic
      efficacy and adverse effects related to intrathecal betamethasone were observed.
      RESULTS: Long-lasting analgesia (mean numerical pain score < or = 5) for 7 days,
      after immediate analgesia within 10 min, was obtained without the need to
      increase the morphine dose in 5 of 10 patients. In almost all of the patients,
      not only pain, but also uncomfortable symptoms were improved. Adverse effects
      related to neurotoxicity of intrathecal betamethasone, such as sensory and motor
      dysfunctions, were not observed in any patients. CONCLUSION: When conventional
      cancer pain treatments are not successful, intrathecal betamethasone may be
      useful, as it probably induces long-lasting analgesia without adverse effects and
      improves activities of daily living, especially in patients with vertebral bone
      metastases.

PMID- 17227819
TI  - Influence of acute normovolaemic haemodilution on the dose-response relationship
      and time course of action of cisatracurium besylate.
AB  - BACKGROUND: Acute normovolaemic haemodilution (ANH) is an efficacious blood
      conservation strategy aiming at avoiding allogeneic blood transfusion. ANH was
      shown to increase the potency of vecuronium, atracurium, and rocuronium. The aim
      of our study was to investigate whether cisatracurium potency is altered with
      ANH. METHODS: Using the Relaxometer mechanomyograph, we compared cisatracurium
      dose-response relationship and time course of action in 60 patients randomly
      allocated to the ANH or control groups. Patients in each group were randomly
      allocated to receive one of three cisatracurium doses (30, 40, 50 microg kg(-1))
      followed by a second supplemental dose to reach a total of 100 microg kg(-1).
      RESULTS: ANH did not result in a significant shift in cisatracurium log dose
      probit dose-response curve. There was no significant difference in mean (95%
      confidence intervals) ED(50), ED(90), and ED(95) (effective doses required for
      50, 90, and 95% first twitch depression) between the ANH group [29.5 (27-32),
      50.4 (47.4-53.4), 58.7 (55.3-62) microg kg(-1)] and the control group [28.2 (25.3
      31), 47.6 (44.9-50.3), 55.3 (52.5-58.1) microg kg(-1)], whereas there was no
      difference in mean (SD) Dur(25) and Dur(0.8) (time until 25% first twitch and 0.8
      train-of-four ratio recoveries) between the ANH group [40.8 (5.9), 64.7 (8.4)
      min] and the control group [42.2 (7.6), 66.5 (10.7) min]. CONCLUSIONS: Our
      results demonstrated that unlike other previously reported neuromuscular blocking
      drugs, ANH did not alter cisatracurium potency. Thus, cisatracurium would be the
      neuromuscular blocking drug of choice in patients who undergo surgery with ANH,
      as no dose adjustments are required.

PMID- 17227820
TI  - CpG-B ODNs potently induce low levels of IFN-alphabeta and induce IFN-alphabeta
      dependent MHC-I cross-presentation in DCs as effectively as CpG-A and CpG-C ODNs.
AB  - Deoxycytidyl-deoxyguanosine [(CpG)3] oligodeoxynucleotides (ODNs) signal through
      TLR9 to induce type-I IFN (IFN-alphabeta) and IFN-alphabeta-dependent MHC-I cross
      presentation of exogenous antigens by dendritic cells (DCs). A puzzle was
      presented by our observation that three ODN classes, CpG-A, CpG-B, and CpG-C, had
      similar efficacy for induction of IFN-alphabeta-dependent MHC-I antigen cross
      presentation by myeloid DCs despite greatly differing for induction of IFN
      alphabeta (CpG-A>CpG-C>>CpG-B). All ODN classes similarly enhanced plasmacytoid
      DC (pDC) presentation of exogenous MHC-I-restricted peptide, although pDCs did
      not cross-process protein antigen. MHC-I and the transporter for antigen
      presentation were induced by all ODN classes or IFN-alpha. CpG-B ODNs were
      slightly more potent than CpG-A or CpG-C ODNs for induction of low levels of IFN
      alphabeta but less efficacious at high concentrations than CpG-A or CpG-C ODNs.
      Low levels of IFN-alphabeta induced by CpG-B ODNs sufficed for full induction of
      MHC-I cross-presentation. Thus, CpG-B ODNs are slightly more potent but less
      efficacious than CpG-A and CpG-C ODNs for induction of IFN-alphabeta. High
      sensitivity to IFN-alphabeta allows CpG-B ODNs to be equally efficacious for
      induction of MHC-I cross-presentation. CpG-B ODNs may be effective for inducing
      therapeutic responses that require low levels of IFN-alphabeta and may avoid
      unnecessarily high induction of IFN-alphabeta.

PMID- 17227821
TI  - Immune complexes suppress IFN-gamma signaling by activation of the FcgammaRI
      pathway.
AB  - Antigen-driven immune responses are modulated by immune complexes (ICs), in part
      through their ability to inhibit IFN-gamma-dependent MHC Class II expression. We
      have demonstrated previously that ICs dramatically inhibit IFN-gamma-induced
      activation of human monocytes through the suppression of the JAK/STAT signaling
      pathway. In the current study, we further explore the mechanisms by which ICs
      regulate IFN-gamma activation of human monocytes. Consistent with previous
      studies in monocytes pretreated with ICs, there was a reduction in steady-state
      levels of RNA by real-time RT-PCR of the IFN-inducible protein 10 gene as well as
      the FcgammaRI gene. Pull-down assays confirm that IC pretreatment inhibits IFN
      gamma-induced STAT1 phosphorylation without affecting the ability of STAT1 to
      bind to the STAT1-binding domain of the IFN-gamma receptor. In addition, the
      inhibitory function of ICs was reduced when cells from the FcR common gamma-chain
      knockout mice were used, supporting the role of the FcgammaRI in this inhibitory
      pathway. It is unexpected that ICs also require the phosphatase Src homology-2
      containing tyrosine phosphatase 1 (SHP-1) to inhibit IFN-gamma induction, as
      demonstrated by studies with cells from the SHP-1 knockout (motheaten) mice.
      These data suggest a mechanism of IC-mediated inhibition of IFN-gamma signaling,
      which requires the ITAM-containing FcgammaRI, as well as the ITIM-dependent
      phosphatase SHP-1, ultimately resulting in the suppression of STAT1
      phosphorylation.

PMID- 17227822
TI  - Signaling requirements for translocation of P-Rex1, a key Rac2 exchange factor
      involved in chemoattractant-stimulated human neutrophil function.
AB  - PI 3,4,5-trisphosphate [PI(3,4,5)P3; PIP3]-dependent Rac exchanger 1 (P-Rex1) is
      a Rac-specific guanine nucleotide exchange factor abundant in neutrophils and
      myeloid cells. As a selective catalyst for Rac2 activation, P-Rex1 serves as an
      important regulator of human neutrophil NADPH oxidase activity and chemotaxis in
      response to a variety of extracellular stimuli. The exchange activity of P-Rex1
      is synergistically activated by the binding of PIP3 and betagamma subunits of
      heterotrimeric G proteins in vitro, suggesting that the association of P-Rex1
      with membranes is a prerequisite for cellular activation. However, the spatial
      regulation of endogenous P-Rex1 has not been well defined, particularly in human
      neutrophils activated through G protein-coupled receptors. Upon stimulation of
      neutrophil chemoattractant receptors, we observed that P-Rex1 translocated from
      cytoplasm to the leading edge of polarized cells in a G protein betagamma subunit
      and PIP3-dependent manner, where it colocalized with F-actin and its substrate,
      Rac2. Redistribution of P-Rex1 to the leading edge was also dependent on tyrosine
      kinase activity and was modulated by cell adhesion. Furthermore, we observed that
      activation of cAMP-dependent protein kinase A (PKA), which phosphorylates and
      inactivates P-Rex1, inhibited its translocation. Our data indicate that
      endogenous P-Rex1 translocates to areas of Rac2 and cytoskeletal activation at
      the leading edge in response to chemoattractant stimuli in human neutrophils and
      that this translocation can be negatively modulated by activation of PKA and by
      cell adhesion.

PMID- 17227823
TI  - JAK kinases control IL-5 receptor ubiquitination, degradation, and
      internalization.
AB  - IL-5, IL-3, and GM-CSF are related hematopoietic cytokines, which regulate the
      function of myeloid cells and are mediators of the allergic inflammatory
      response. These cytokines signal through heteromeric receptors containing a
      specific alpha chain and a shared signaling chain, betac. Previous studies
      demonstrated that the ubiquitin (Ub) proteasome degradation pathway was involved
      in signal termination of the betac-sharing receptors. In this study, the upstream
      molecular events leading to proteasome degradation of the IL-5 receptor (IL-5R)
      were examined. By using biochemical and flow cytometric methods, we show that JAK
      kinase activity is required for betac ubiquitination and proteasome degradation
      but only partially required for IL-5R internalization. Furthermore, we
      demonstrate the direct ubiquitination of the betac cytoplasmic domain and
      identify lysine residues 566 and 603 as sites of betac ubiquitination. Lastly, we
      show that ubiquitination of the betac cytoplasmic domain begins at the plasma
      membrane, increases after receptor internalization, and is degraded by the
      proteasome after IL-5R internalization. We propose an updated working model of IL
      5R down-regulation, whereby IL-5 ligation of its receptor activates JAK2/1
      kinases, resulting in betac tyrosine phosphorylation, ubiquitination, and IL-5R
      internalization. Once inside the cell, proteasomes degrade the betac cytoplasmic
      domain, and the truncated receptor complex is terminally degraded in the
      lysosomes. These data establish a critical role for JAK kinases and the
      Ub/proteasome degradation pathway in IL-5R down-regulation.

PMID- 17227824
TI  - Parapharyngeal abscess in a patient receiving etanercept.
AB  - OBJECTIVE: To report a case of parapharyngeal abscess associated with
      Streptococcus viridans in a patient with rheumatoid arthritis receiving treatment
      with etanercept. CASE SUMMARY: A 40-year-old man diagnosed with rheumatoid
      arthritis had received treatment with nonsteroidal antiinflammatory drugs,
      methotrexate, and deflazacort. Six months prior to admission, the patient had a
      Disease Activity Score of 3.4; clinicians decided to start treatment with
      etanercept. Chest X-rays were normal and the tuberculin skin test was negative.
      Treatment with etanercept plus methotrexate was started. Three months later,
      methotrexate was discontinued. Six months after etanercept therapy was started,
      the patient presented to our emergency department with a swelling of his neck,
      odynophagia, otalgia, and trismus. The clinical course was consistent with
      parapharyngeal abscess. Etanercept treatment was suspended. The parapharyngeal
      abscess was drained and intravenous methylprednisolone, amoxicillin/clavulanic
      acid, and clindamycin were administered. The parapharyngeal abscess secretion
      culture was positive for S. viridans and Bacteroides spp. The patient's condition
      improved with antibiotic therapy; he was discharged 5 days after admission.
      DISCUSSION: Tumor necrosis factor-alpha plays an essential role in the immune
      mediated response to infection. In our patient, the most possible cause of
      parapharyngeal abscess was considered to be etanercept because of the temporal
      relationship between exposure to the drug and onset of symptoms. Etanercept was
      the only drug administered before the abscess developed. Based on the Naranjo
      probability scale, an association between etanercept and the adverse reaction
      could be considered possible. CONCLUSIONS: Patients initiated on etanercept
      therapy should be closely monitored for the development of tuberculosis and other
      infections. During treatment, all febrile or novel illnesses should be evaluated
      promptly. If clinical evaluation leads to the suspicion of tuberculosis and other
      infections associated with etanercept, it should be discontinued immediately.

PMID- 17227825
TI  - Tegaserod for treating chronic constipation in elderly patients.
AB  - OBJECTIVE: To evaluate data that address the safety and efficacy of tegaserod for
      the management of chronic constipation (CC) in elderly patients. DATA SOURCES:
      Primary literature was identified through MEDLINE (1966-January 2007) and EMBASE
      (2002-January 2007) using the search terms tegaserod, elderly, and constipation.
      Additional information was requested from the pharmaceutical manufacturer. STUDY
      SELECTION AND DATA EXTRACTION: Clinical trials evaluating the efficacy and safety
      of tegaserod for treating CC were considered for inclusion. Emphasis was placed
      on data relevant to use of tegaserod in the elderly and on CC. DATA SYNTHESIS:
      Two efficacy trials evaluated tegaserod for treating constipation. They enrolled
      a total of 331 elderly patients, comprising approximately 13% of study patients.
      Tegaserod was effective for improving constipation in the overall study
      populations; no significant adverse events were noted. However, both studies
      lacked a subgroup analysis in the elderly. Diarrhea occurred more commonly with
      higher doses of tegaserod and may be a concern in older adults. A 13 month safety
      trial found tegaserod to be well tolerated for treatment of constipation, with
      similar adverse events seen as in the 12 week efficacy studies. Specific data
      were not provided for elderly patients. CONCLUSIONS: Tegaserod should not replace
      current therapies for treatment of CC in the elderly. The drug has been studied
      in a small number of older adults; thus, data are inconclusive about its use in
      this population. Older adults have a higher risk of diarrhea with tegaserod.
      Cautious use is warranted until further studies specifically address the elderly
      population.

PMID- 17227826
TI  - Nur77 converts phenotype of Bcl-B, an antiapoptotic protein expressed in plasma
      cells and myeloma.
AB  - Defects in apoptosis mechanisms play important roles in malignancy and
      autoimmunity. Orphan nuclear receptor Nur77/TR3 has been demonstrated to bind
      antiapoptotic protein Bcl-2 and convert it from a cytoprotective to a
      cytodestructive protein, representing a phenotypic conversion mechanism. Of the 6
      antiapoptotic human Bcl-2 family members, we found that Nur77/TR3 binds strongest
      to Bcl-B, showing selective reactivity with Bcl-B, Bcl-2, and Bfl-1 but not Bcl
      X(L), Mcl-1, or Bcl-W. Nur77 converts the phenotype of Bcl-B from antiapoptotic
      to proapoptotic. Bcl-B is prominently expressed in plasma cells and multiple
      myeloma. Endogenous Bcl-B associates with endogenous Nur77 in RPMI 8226 myeloma
      cells, where RNA interference experiments demonstrated dependence on Bcl-B for
      Nur77-induced apoptosis. Furthermore, a Nur77-mimicking peptide killed RPMI 8226
      myeloma cells through a Bcl-B-dependent mechanism. Because Bcl-B is abundantly
      expressed in plasma cells and some myelomas, these findings raise the possibility
      of exploiting the Nur77/Bcl-B mechanism for apoptosis for eradication of
      autoimmune plasma cells or myeloma.

PMID- 17227827
TI  - Deficiency of Bim in dendritic cells contributes to overactivation of lymphocytes
      and autoimmunity.
AB  - Apoptosis in dendritic cells (DCs) can potentially regulate DC homeostasis and
      immune responses. We have previously observed that inhibition of the Fas
      signaling pathway in DCs results in spontaneous T-cell activation and the
      development of systemic autoimmunity in transgenic mice. However, the role for
      different apoptosis pathways in DCs in regulating DC homeostasis and immune
      tolerance remains to be determined. Bim, a BH3-only protein of the Bcl-2 family,
      was expressed at low levels in DCs and was significantly up-regulated by
      signaling from CD40 or toll-like receptors (TLRs). Because Bim(-/-) mice develop
      spontaneous systemic autoimmunity, we investigated whether Bim(-/-) DCs
      contributed to lymphoproliferation and autoimmunity in these mice. Bim(-/-) DCs
      showed decreased spontaneous cell death, and induced more robust T-cell
      activation in vitro and in vivo. Moreover, Bim(-/-) DCs induced autoantibody
      production after adoptive transfer. Our data suggest that Bim is important for
      regulating spontaneous cell death in DCs, and Bim-deficient DCs may contribute to
      the development of autoimmune diseases in Bim(-/-) mice.

PMID- 17227828
TI  - Nonredundant roles for Stat5a/b in directly regulating Foxp3.
AB  - Stats (signal transducers and activators of transcription) regulate multiple
      aspects of T-cell fate. T regulatory (Treg) cells are a critical subset that
      limits immune responses, but the relative importance of Stat5a/b versus Stat3 for
      Treg cell development has been contentious. We observed that peripheral
      CD25(+)CD4(+) T cells were reduced in Stat5(DeltaN) mice; however, the levels of
      Foxp3, a transcription factor that is critical for Treg cells, were normal in
      splenic CD4(+) T cells even though they were reduced in the thymus. In contrast,
      complete deletion of Stat5a/b (Stat5(-/-)) resulted in dramatic reduction in CD25
      or Foxp3-expressing CD4(+) T cells. An intrinsic requirement was demonstrated by
      reduction of Stat5a/b in CD4-expressing cells and by stem cell transplantation
      using Stat5(-/-) fetal liver cells. Stat5a/b were also required for optimal
      induction of Foxp3 in vitro and bound directly to the Foxp3 gene. Reduction of
      Stat3 in T cells did not reduce the numbers of Treg cells in the thymus or
      spleen; however, Stat3 was required for IL-6-dependent down-regulation of Foxp3.
      Therefore, we conclude that Stat5a/b have an essential, nonredundant role in
      regulating Treg cells, and that Stat3 and Stat5a/b appear to have opposing roles
      in the regulation of Foxp3.

PMID- 17227829
TI  - Factors governing the activation of adoptively transferred donor T cells infused
      after allogeneic bone marrow transplantation in the mouse.
AB  - Murine models of bone marrow transplantation were used to study the mechanisms
      governing the activation of donor lymphocyte infusions (DLIs) manifesting as
      lymphohematopoietic graft-versus-host (LH-GVH) and graft-versus-leukemia (GVL)
      reactivities. We demonstrate here that established mixed chimerism influences the
      potency of DLI-mediated alloreactivity only in the MHC-mismatched but not MHC
      matched setting. In the MHC-matched setting, high levels (>or= 40%) of residual
      host chimerism correlated negatively with DLI-mediated alloreactivity
      irrespective of the timing of their administration, the donor's previous
      sensitization to host antigens, or the level of residual host APCs. In vivo
      administration of Toll-like receptor (TLR) ligands was required to maximize DLI
      mediated LH-GVH and GVL reactivities in chimeras with low levels (<or= 15%) of
      residual host chimerism. In contrast, coadministration of DLI with antigen
      presenting cell (APC) activators was insufficient to augment their LH-GVH
      response in the presence of high levels of host chimerism unless the host's T
      cells were transiently depleted. Together, these results show the cardinal
      influence of donor-host incompatibility on DLI-mediated GVH responses and suggest
      that in MHC-matched chimeras, the induction of optimal alloreactivity requires
      not only donor T cells and host APCs but also TLR ligands and in the presence of
      high levels of host chimerism depletion of host T cells.

PMID- 17227830
TI  - CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and
      predict clinical outcome in patients with acute myeloid leukemia treated with
      gemtuzumab ozogamicin monotherapy.
AB  - Gemtuzumab ozogamicin (GO) contains an anti-CD33 antibody to facilitate uptake of
      a toxic calicheamicin-gamma(1) derivative. While recent in vitro data
      demonstrated a quantitative relationship between CD33 expression and GO
      cytotoxicity, previous correlative studies failed to identify a significant
      association between CD33 expression and clinical outcome. Studying patients
      undergoing GO monotherapy for relapsed acute myeloid leukemia (AML), we now find
      that AML blasts of responders have a significantly higher mean CD33 level and
      lower P-glycoprotein (Pgp) activity compared with nonresponders. CD33 expression
      and Pgp activity are inversely correlated. While both variables are associated
      with outcome, Pgp remains significantly associated with outcome even after
      adjusting for CD33, whereas CD33 does not show such an association after
      adjusting for Pgp. The inverse relationship between CD33 and Pgp suggests a
      maturation-stage-dependent expression of both proteins, and offers the rationale
      for using cell differentiation-promoting agents to enhance GO-induced
      cytotoxicity.

PMID- 17227831
TI  - Osteoblasts support B-lymphocyte commitment and differentiation from
      hematopoietic stem cells.
AB  - Early B lymphopoiesis in mammals is induced within the bone marrow (BM)
      microenvironment, but which cells constitute this niche is not known. Previous
      studies had shown that osteoblasts (OBs) support hematopoietic stem cell (HSC)
      proliferation and myeloid differentiation. We now find that purified primary
      murine OBs also support the differentiation of primitive hematopoietic stem cells
      through lymphoid commitment and subsequent differentiation to all stages of B
      cell precursors and mature B cells. Lin(-)Sca-1(+)Rag-2(-) BM cell
      differentiation to B cells requires their attachment to OBs in vitro, and this
      developmental process is mediated via VCAM-1, SDF-1, and IL-7 signaling induced
      by parathyroid hormone (PTH). Addition of cytokines produced by nonosteoblastic
      stromal cells (c-Kit ligand, IL-6, and IL-3) shifted the cultures toward
      myelopoiesis. Confirming the role of OBs in B lymphopoiesis, we found that
      selective elimination of osteoblasts in Col2.3Delta-TK transgenic mice severely
      depleted pre-pro-B and pro-B cells from BM, preceding any decline in HSCs. Taken
      together, these results demonstrate that osteoblasts are both necessary and
      sufficient for murine B-cell commitment and maturation, and thereby constitute
      the cellular homolog of the avian bursa of Fabricius.

PMID- 17227832
TI  - Trib1 and Evi1 cooperate with Hoxa and Meis1 in myeloid leukemogenesis.
AB  - Cooperative activation of Meis1 and Hoxa9 perturbs myeloid differentiation and
      eventually leads myeloid progenitors to leukemia, yet it remains to be clarified
      what kinds of subsequent molecular processes are required for development of
      overt leukemia. To understand the molecular pathway in Hoxa9/Meis1-induced
      leukemogenesis, retroviral insertional mutagenesis was applied using retrovirus
      mediated gene transfer. The mice that received Hoxa9/Meis1-transduced bone marrow
      cells developed acute myeloid leukemia (AML), and Trib1, Evi1, Ahi1, Raralpha,
      Pitpnb, and AK039950 were identified as candidate cooperative genes located near
      common retroviral integration sites. Trib1 and Evi1 were up-regulated due to
      retroviral insertions, and coexpression of these genes significantly accelerated
      the onset of Hoxa9/Meis1-induced AML, suggesting that Trib1 and Evi1 are the key
      collaborators. Furthermore, Trib1 by itself is a novel myeloid oncogene,
      enhancing phosphorylation of ERK, resulting in inhibition of apoptosis. These
      results demonstrate the importance of specific oncogene interaction in myeloid
      leukemogenesis.

PMID- 17227833
TI  - Activation of the Hedgehog signaling pathway in T-lineage cells inhibits TCR
      repertoire selection in the thymus and peripheral T-cell activation.
AB  - TCR signal strength is involved in many cell fate decisions in the T-cell
      lineage. Here, we show that transcriptional events induced by Hedgehog (Hh)
      signaling reduced TCR signal strength in mice. Activation of Hh signaling in
      thymocytes in vivo by expression of a transgenic transcriptional-activator form
      of Gli2 (Gli2DeltaN(2)) changed the outcome of TCR ligation at many stages of
      thymocyte development, allowing self-reactive cells to escape clonal deletion;
      reducing transgenic TCR-mediated positive selection; reducing the ratio of
      CD4/CD8 single-positive (SP) cells; and reducing cell surface CD5 expression. In
      contrast, in the Shh(-/-) thymus the ratio of CD4/CD8 cells and both positive and
      negative selection of a transgenic TCR were increased, demonstrating that Shh
      does indeed influence TCR repertoire selection and the transition from double
      positive (DP) to SP cell in a physiological situation. In peripheral T cells,
      Gli2DeltaN(2) expression attenuated T-cell activation and proliferation, by a
      mechanism upstream of ERK phosphorylation.

PMID- 17227835
TI  - The BH3-mimetic GX15-070 synergizes with bortezomib in mantle cell lymphoma by
      enhancing Noxa-mediated activation of Bak.
AB  - Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma resistant to
      conventional chemotherapy. The Bcl-2 pathway is deregulated in these tumors and
      may represent an interesting target for new therapeutic strategies. The new small
      molecule pan-Bcl-2 inhibitor GX15-070 mimics BH3-only proteins by binding to
      multiple antiapoptotic Bcl-2 members. Here we show that GX15-070 induced
      apoptosis in vitro in MCL cell lines and primary cells from patients with MCL by
      releasing Bak from Mcl-1 and Bcl-X(L) at short incubation times and low
      micromolar doses. GX15-070 was effective in cells bearing defective DNA damage
      sensor genes or cell-cycle regulators, inducing Bax and Bak conformational
      changes, mitochondrial depolarization, phosphatidylserine exposure, and caspase-3
      activation. Furthermore, GX15-070 synergized with bortezomib, sensitizing MCL
      cells to low doses of this proteasome inhibitor, by neutralizing bortezomib
      induced Mcl-1 accumulation and cooperating with Noxa to induce Bak displacement
      from this protein. These events led to an increased activation of the
      mitochondrial apoptotic pathway. Importantly, GX15-070 alone or in combination
      with bortezomib showed no significant cytotoxic effect in peripheral blood
      mononuclear cells from healthy donors. All these findings suggest that GX15-070
      alone or in combination with bortezomib represents a new attractive therapeutic
      approach for MCL treatment.

PMID- 17227834
TI  - Relative antithrombotic and antihemostatic effects of protein C activator versus
      low-molecular-weight heparin in primates.
AB  - The anticoagulant and anti-inflammatory enzyme, activated protein C (APC),
      naturally controls thrombosis without affecting hemostasis. We therefore
      evaluated whether the integrity of primary hemostasis was preserved during
      limited pharmacological antithrombotic protein C activator (PCA) treatment in
      baboons. The double-mutant thrombin (Trp215Ala/Glu217Ala) with less than 1%
      procoagulant activity was used as a relatively selective PCA and compared with
      systemic anticoagulation by APC and low-molecular-weight heparin (LMWH) at doses
      that inhibited fibrin deposition on thrombogenic segments of arteriovenous
      shunts. As expected, both systemic anticoagulants, APC (0.028 or 0.222 mg/kg for
      70 minutes) and LMWH (0.325 to 2.6 mg/kg for 70 minutes), were antithrombotic and
      prolonged the template bleeding time. In contrast, PCA at doses (0.0021 to 0.0083
      mg/kg for 70 minutes) that had antithrombotic effects comparable with LMWH did
      not demonstrably impair primary hemostasis. PCA bound to platelets and
      leukocytes, and accumulated in thrombi. APC infusion at higher circulating APC
      levels was less antithrombotic than PCA infusion at lower circulating APC levels.
      The observed dissociation of antithrombotic and antihemostatic effects during PCA
      infusion thus appeared to emulate the physiological regulation of intravascular
      blood coagulation (thrombosis) by the endogenous protein C system. Our data
      suggest that limited pharmacological protein C activation might exhibit
      considerable thrombosis specificity.

PMID- 17227836
TI  - Exposure to mercury in the mine of Almaden.
AB  - OBJECTIVES: To describe the process for obtaining mercury and the historical
      exposure of Almaden miners to mercury. METHODS: Information on every workplace
      and historical data on production, technological changes in the productive
      process and biological and environmental values of mercury was collected. A job
      exposure matrix was built with these values and the exposure to inorganic mercury
      was estimated quantitatively as mug/l of urine mercury. A cumulative exposure
      index was calculated for every worker by adding the estimates for every year in
      the different workplaces. RESULTS: In the mine, the highest exposures occurred
      during drilling, with values up to 2.26 mg/m3 in air, 2194 microg/l in urine and
      374 microg/l in blood. Furnace operation and cleaning were the tasks with the
      highest values in metallurgy, peaking up to 3.37 mg/m3. The filling of bottles
      with mercury by free fall gave values within a range of 1.13-2.43 mg/m3 in air;
      these values dropped to 0.32-0.83 mg/m3 after introducing a new ventilation
      system. The toxicity effects of high doses of inorganic mercury on the central
      nervous and urinary systems have been known for decades. CONCLUSIONS: The
      exposure of the workers in Almaden mines to mercury has been very high. The
      extremely high content cinnabar ore of the mine explains the increased
      concentrations of mercury in air at the work places. This, together with
      inadequate working conditions, explains the high mercury levels found in blood
      and urine during the study period.

PMID- 17227837
TI  - Inter-rater agreement in the assessment of exposure to carcinogens in the
      offshore petroleum industry.
AB  - OBJECTIVES: To evaluate the reliability of an expert team assessing exposure to
      carcinogens in the offshore petroleum industry and to study how the information
      provided influenced the agreement among raters. METHODS: Eight experts
      individually assessed the likelihood of exposure for combinations of 17
      carcinogens, 27 job categories and four time periods (1970-1979, 1980-1989, 1990
      1999 and 2000-2005). Each rater assessed 1836 combinations based on summary
      documents on carcinogenic agents, which included descriptions of sources of
      exposure and products, descriptions of work processes carried out within the
      different job categories, and monitoring data. Inter-rater agreement was
      calculated using Cohen's kappa index and single and average score intraclass
      correlation coefficients (ICC) (ICC(2,1) and ICC(2,8), respectively). Differences
      in inter-rater agreement for time periods, raters, International Agency for
      Research on Cancer groups and the amount of information provided were
      consequently studied. RESULTS: Overall, 18% of the combinations were denoted as
      possible exposure, and 14% scored probable exposure. Stratified by the 17
      carcinogenic agents, the probable exposure prevalence ranged from 3.8% for
      refractory ceramic fibres to 30% for crude oil. Overall mean kappa was 0.42
      (ICC(2,1) = 0.62 and ICC(2,8) = 0.93). Providing limited quantitative measurement
      data was associated with less agreement than for equally well described
      carcinogens without sampling data. CONCLUSION: The overall kappa and single-score
      ICC indicate that the raters agree on exposure estimates well above the chance
      level. The levels of inter-rater agreement were higher than in other comparable
      studies. The average score ICC indicates reliable mean estimates and implies that
      sufficient raters were involved. The raters seemed to have enough documentation
      on which to base their estimates, but provision of limited monitoring data leads
      to more incongruence among raters. Having real exposure data, with the inherent
      variability of such data, apparently makes estimating exposure in a rigid
      semiquantitative manner more difficult.

PMID- 17227838
TI  - Cancer mortality in a synthetic spinning plant in Besancon, France.
AB  - OBJECTIVES: To assess the mortality of a cohort of workers in a synthetic textile
      spinning plant and to evaluate the relationship between mortality from lung,
      liver and bladder cancer and the processes or the products used. METHODS: The
      study population consisted of male workers present for at least 6 months in the
      plant from 1968 to 1984. The cohort was followed until 1999. Vital status and the
      causes of death were determined by consulting national registries. The population
      of the Franche-Comte region was used for comparison. In total, 17 groups of
      exposure were assessed by the industrial hygienist, based on the consensus of an
      expert group that determined the exposure levels of each job to selected
      occupational hazards. Each worker was assigned to one or several groups,
      according to his occupational history. Confounding factors could not be assessed.
      Standardised mortality ratios (SMR) and 95% bilateral confidence intervals were
      calculated based on an assumed Poisson distribution of the number of cases to
      compare the plant mortality and the population mortality. Internal analyses were
      performed with Cox models in order to assess the risks of death related to the
      various exposures. RESULTS: In the whole cohort, mortality from all malignant
      neoplasms was lower than expected, but this was not significant. All the
      estimated SMRs were lower than or close to 1. The "hot -line fitters" (RR = 2.13;
      n = 9; 1.06 to 4.29) and the "fibre-drawing workers" (RR = 1.83; n = 20;1.09 to
      3.07) experienced a statistically significant excess in mortality from lung
      cancer. A slightly elevated but not significant risk of death related to lung
      cancer (RR = 1.5; n = 41; 0.8 to 2.7) was observed in the groups with the highest
      exposure to mineral fibres. A statistically significant increase in cancer deaths
      was observed for workers with high exposure to dust (higher intensity: RR = 1.42;
      n = 79; 1.06 to 1.89). CONCLUSION: Some findings, mainly of lung cancer, justify
      further exploration in other plants in this industry.

PMID- 17227839
TI  - Wrinkled hard skins on polymers created by focused ion beam.
AB  - A stiff skin forms on surface areas of a flat polydimethylsiloxane (PDMS) upon
      exposure to focused ion beam (FIB) leading to ordered surface wrinkles. By
      controlling the FIB fluence and area of exposure of the PDMS, one can create a
      variety of patterns in the wavelengths in the micrometer to submicrometer range,
      from simple one-dimensional wrinkles to peculiar and complex hierarchical nested
      wrinkles. Examination of the chemical composition of the exposed PDMS reveals
      that the stiff skin resembles amorphous silica. Moreover, upon formation, the
      stiff skin tends to expand in the direction perpendicular to the direction of ion
      beam irradiation. The consequent mismatch strain between the stiff skin and the
      PDMS substrate buckles the skin, forming the wrinkle patterns. The induced
      strains in the stiff skin are estimated by measuring the surface length in the
      buckled state. Estimates of the thickness and stiffness of the stiffened surface
      layer are estimated by using the theory for buckled films on compliant
      substrates. The method provides an effective and inexpensive technique to create
      wrinkled hard skin patterns on surfaces of polymers for various applications.

PMID- 17227840
TI  - Constitutively high dNTP concentration inhibits cell cycle progression and the
      DNA damage checkpoint in yeast Saccharomyces cerevisiae.
AB  - In eukaryotic cells the concentration of dNTP is highest in S phase and lowest in
      G1 phase and is controlled by ribonucleotide reductase (RNR). RNR activity is
      eliminated in all eukaryotes in G1 phase by a variety of mechanisms:
      transcriptional regulation, small inhibitory proteins, and protein degradation.
      After activation of RNR upon commitment to S phase, dATP feedback inhibition
      ensures that the dNTP concentration does not exceed a certain maximal level. It
      is not apparent why limitation of dNTP concentration is necessary in G1 phase. In
      principle, dATP feedback inhibition should be sufficient to couple dNTP
      production to utilization. We demonstrate that in Saccharomyces cerevisiae
      constitutively high dNTP concentration transiently arrests cell cycle progression
      in late G1 phase, affects activation of origins of replication, and inhibits the
      DNA damage checkpoint. We propose that fluctuation of dNTP concentration controls
      cell cycle progression and the initiation of DNA replication.

PMID- 17227841
TI  - Core-controlled polymorphism in virus-like particles.
AB  - This study concerns the self-assembly of virus-like particles (VLPs) composed of
      an icosahedral virus protein coat encapsulating a functionalized spherical
      nanoparticle core. The recent development of efficient methods for VLP self
      assembly has opened the way to structural studies. Using electron microscopy with
      image reconstruction, the structures of several VLPs obtained from brome mosaic
      virus capsid proteins and gold nanoparticles were elucidated. Varying the gold
      core diameter provides control over the capsid structure. The number of subunits
      required for a complete capsid increases with the core diameter. The packaging
      efficiency is a function of the number of capsid protein subunits per gold
      nanoparticle. VLPs of varying diameters were found to resemble to three classes
      of viral particles found in cells (T=1, 2, and 3). As a consequence of their
      regularity, VLPs form three-dimensional crystals under the same conditions as the
      wild-type virus. The crystals represent a form of metallodielectric material that
      exhibits optical properties influenced by multipolar plasmonic coupling.

PMID- 17227842
TI  - BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein, is required
      for correct glycosylation and function of integrin beta1.
AB  - Glycosylation of beta1 integrin (beta1) in the Golgi complex has been related to
      its function in multiple cell processes, e.g., invasiveness, matrix adhesion, and
      migration. Brefeldin A-inhibited guanine nucleotide-exchange proteins (BIG) 1 and
      BIG2 activate human ADP-ribosylation factors (ARF) 1 and ARF3 by catalyzing the
      replacement of ARF-bound GDP with GTP to regulate Golgi vesicular transport. We
      show here a requirement for BIG1 (but not BIG2) in glycosylation and function of
      beta1. In HepG2 cells treated for 48 or 72 h with BIG1, but not BIG2, siRNA, both
      the amount and electrophoretic mobility of the initially 130-kDa beta1 were
      increased. BIG1 content had risen by 48 h after removal of BIG1 siRNA, and the
      faster-migrating, aberrant 130-kDa beta1 was not seen. Peptide N-glycosidase F,
      but not endoglycosidase H, digestion converted all beta1 to an approximately 85
      kDa (core protein) form. By electron microscopy, Golgi membranes in BIG1-depleted
      cells were less sharply defined than those in mock or BIG2 siRNA-treated cells,
      with more vesicle-like structures at the transface. Amounts of active RhoA-GTP
      also were decreased in such cells and restored by overexpression of HA-BIG1.
      Aberrant beta1 was present on the cell surface, but its function in cell
      spreading, adhesion, and migration was impaired. By immunofluorescence
      microscopy, BIG1 siRNA-treated cells showed less spreading and concentration of
      beta1 at the cell surface. These results indicate a previously unrecognized role
      for BIG1 in the glycosylation of beta1 by Golgi enzymes, which is critical for
      its function in developmental and other vital cell processes.

PMID- 17227843
TI  - The neck of caveolae is a distinct plasma membrane subdomain that concentrates
      insulin receptors in 3T3-L1 adipocytes.
AB  - Insulin receptors (IRs) segregate on plasma membrane microvilli, but in cells
      devoid of microvilli, such as adipocytes, the localization of IRs is a matter of
      controversy. In the present study, we examined the distribution of IRs in the
      plasma membrane of 3T3-L1 adipocytes. Quantitative electron microscopy indicates
      that IRs are predominantly associated with the neck, but not the bulb, of
      caveolae. Caveola necks represent distinct microdomains of the plasma membrane.
      Indeed, as shown by freeze-fracture analysis, intramembrane particles are
      concentrated as necklaces around the craters of caveolae. In addition,
      subcellular fractionation suggests that the neck and the bulb of caveolae present
      a different resistance to detergent solubility. Finally, cytoskeletal components,
      including actin, are highly enriched in the membrane area underlying the neck
      part of caveolae. IRs coimmunoprecipitate with cytoskeletal components, and
      disruption of the actin cytoskeleton alters IRs expression, localization, and
      signaling, thus supporting the notion that caveola necks are involved in
      intracellular signaling by IRs. Together, these results suggest that cytoskeletal
      proteins anchor IRs to microdomains in the caveola necks of 3T3-L1 adipocytes. By
      homology with IR localization in other cell types, we suggest that the necks of
      caveolae may represent the counterpart of microvillar domains in cells poor in
      microvilli such as adipocytes and that they play an important role as signaling
      platforms.

PMID- 17227844
TI  - Structural analysis of Bub3 interactions in the mitotic spindle checkpoint.
AB  - The Mad3/BubR1, Mad2, Bub1, and Bub3 proteins are gatekeepers for the transition
      from metaphase to anaphase. Mad3 from Saccharomyces cerevisiae has homology to
      Bub1 but lacks a corresponding C-terminal kinase domain. Mad3 forms a stable
      heterodimer with Bub3. Negative-stain electron microscopy shows that Mad3 is an
      extended molecule (approximately 200 A long), whereas Bub3 is globular. The Gle2
      binding-sequence (GLEBS) motifs found in Mad3 and Bub1 are necessary and
      sufficient for interaction with Bub3. The calorimetrically determined
      dissociation constants for GLEBS-motif peptides and Bub3 are approximately 5
      microM. Crystal structures of these peptides with Bub3 show that the interactions
      for Mad3 and Bub1 are similar and mutually exclusive. In both structures, the
      GLEBS peptide snakes along the top surface of the beta-propeller, forming an
      extensive interface. Mutations in either protein that disrupt the interface cause
      checkpoint deficiency and chromosome instability. We propose that the structure
      imposed on the GLEBS segment by its association with Bub3 enables recruitment to
      unattached kinetochores.

PMID- 17227845
TI  - All four CatSper ion channel proteins are required for male fertility and sperm
      cell hyperactivated motility.
AB  - Mammalian spermatozoa become motile at ejaculation, but before they can fertilize
      the egg, they must acquire more thrust to penetrate the cumulus and zona
      pellucida. The forceful asymmetric motion of hyperactivated spermatozoa requires
      Ca2+ entry into the sperm tail by an alkalinization-activated voltage-sensitive
      Ca2+-selective current (ICatSper). Hyperactivation requires CatSper1 and CatSper2
      putative ion channel genes, but the function of two other related genes (CatSper3
      and CatSper4) is not known. Here we show that targeted disruption of murine
      CatSper3 or CatSper4 also abrogated ICatSper, sperm cell hyperactivated motility
      and male fertility but did not affect spermatogenesis or initial motility. Direct
      protein interactions among CatSpers, the sperm specificity of these proteins, and
      loss of ICatSper in each of the four CatSper-/- mice indicate that CatSpers are
      highly specialized flagellar proteins.

PMID- 17227846
TI  - Aberrant localization and underglycosylation of highly accumulating single-chain
      Fv-Fc antibodies in transgenic Arabidopsis seeds.
AB  - Production of high-value recombinant proteins in transgenic seeds is an
      attractive and economically feasible alternative to conventional systems based on
      mammalian cells and bacteria. In contrast to leaves, seeds allow high-level
      accumulation of recombinant proteins in a relatively small volume and a stable
      environment. We demonstrate that single-chain variable fragment (scFv)-Fc
      antibodies, with N-terminal signal sequence and C-terminal KDEL tag, can
      accumulate to very high levels as bivalent IgG-like antibodies in Arabidopsis
      thaliana seeds and illustrate that a plant-produced anti-hepatitis A virus scFv
      Fc has similar antigen-binding and in vitro neutralizing activities as the
      corresponding full-length IgG. As expected, most scFv-Fc produced in seeds
      contained only oligomannose-type N-glycans, but, unexpectedly, 35-40% was never
      glycosylated. A portion of the scFv-Fc was found in endoplasmic reticulum (ER)
      derived compartments delimited by ribosome-associated membranes. Additionally,
      consistent with the glycosylation data, large amounts of the recombinant protein
      were deposited in the periplasmic space, implying a direct transport from the ER
      to the periplasmic space between the plasma membrane and the cell wall. Aberrant
      localization of the ER chaperones calreticulin and binding protein (BiP) and the
      endogenous seed storage protein cruciferin in the periplasmic space suggests that
      overproduction of recombinant scFv-Fc disturbs normal ER retention and protein
      sorting mechanisms in the secretory pathway.

PMID- 17227847
TI  - Deprivation-induced synaptic depression by distinct mechanisms in different
      layers of mouse visual cortex.
AB  - Long-term depression (LTD) induced by low-frequency synaptic stimulation (LFS)
      was originally introduced as a model to probe potential mechanisms of deprivation
      induced synaptic depression in visual cortex. In hippocampus, LTD requires
      activation of postsynaptic NMDA receptors, PKA, and the clathrin-dependent
      endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      receptors. It has long been assumed that LTD induced in visual cortical layer 2/3
      by LFS of layer 4 uses similar mechanisms. Here we show in mouse visual cortex
      that this conclusion requires revision. We find that LTD induced in layer 2/3 by
      LFS is unaffected by inhibitors of PKA or alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptor endocytosis but is reliably blocked by an
      endocannabinoid CB1 receptor antagonist. Conversely, LFS applied to synapses on
      layer 4 neurons produces LTD that appears mechanistically identical to that in
      CA1 and is insensitive to CB1 blockers. Occlusion experiments suggest that both
      mechanisms contribute to the loss of visual responsiveness after monocular
      deprivation.

PMID- 17227849
TI  - Structure of the monooxygenase component of a two-component flavoprotein
      monooxygenase.
AB  - p-Hydroxyphenylacetate hydroxylase from Acinetobacter baumannii is a two
      component system consisting of a NADH-dependent FMN reductase and a monooxygenase
      (C2) that uses reduced FMN as substrate. The crystal structures of C2 in the
      ligand-free and substrate-bound forms reveal a preorganized pocket that binds
      reduced FMN without large conformational changes. The Phe-266 side chain swings
      out to provide the space for binding p-hydroxyphenylacetate that is oriented
      orthogonal to the flavin ring. The geometry of the substrate-binding site of C2
      is significantly different from that of p-hydroxybenzoate hydroxylase, a single
      component flavoenzyme that catalyzes a similar reaction. The C2 overall structure
      resembles the folding of medium-chain acyl-CoA dehydrogenase. An outstanding
      feature in the C2 structure is a cavity located in front of reduced FMN; it has a
      spherical shape with a 1.9-A radius and a 29-A3 volume and is interposed between
      the flavin C4a atom and the substrate atom to be hydroxylated. The shape and
      position of this cavity are perfectly fit for housing the oxygen atoms of the
      flavin C4a-hydroperoxide intermediate that is formed upon reaction of the C2
      bound reduced flavin with molecular oxygen. The side chain of His-396 is
      predicted to act as a hydrogen-bond donor to the oxygen atoms of the
      intermediate. This architecture promotes the nucleophilic attack of the substrate
      onto the terminal oxygen of the hydroperoxyflavin. Comparative analysis with the
      structures of other flavoenzymes indicates that a distinctive feature of
      monooxygenases is the presence of specific cavities that encapsulate and
      stabilize the crucial hydroperoxyflavin intermediate.

PMID- 17227848
TI  - Long latency of evoked quantal transmitter release from somata of locus coeruleus
      neurons in rat pontine slices.
AB  - The locus coeruleus (LC) harbors a compact group of noradrenergic cell bodies
      projecting to virtually all parts of the central nervous system. By using
      combined measurements of amperometry and patch-clamp, quantal vesicle release of
      noradrenaline (NA) was detected as amperometric spikes, after depolarization of
      the LC neurons. After a pulse depolarization, the average latency of amperometric
      spikes was 1,870 ms, whereas the latency of glutamate-mediated excitatory
      postsynaptic currents was 1.6 ms. A substantial fraction of the depolarization
      induced amperometric spikes originated from the somata. In contrast to glutamate
      mediated excitatory postsynaptic currents, NA secretion was strongly modulated by
      the action potential frequency (0.5-50 Hz). Somatodendritic NA release from LC
      upon enhanced cell activity produced autoinhibition of firing and of NA release.
      We conclude that, in contrast to classic synaptic transmission, quantal NA
      release from LC somata is characterized by a number of distinct properties,
      including long latency and high sensitivity to action potential frequency.

PMID- 17227850
TI  - Id1 restrains myeloid commitment, maintaining the self-renewal capacity of
      hematopoietic stem cells.
AB  - Appropriate hematopoietic stem cell (HSC) self-renewal reflects the tight
      regulation of cell cycle entry and lineage commitment. Here, we show that Id1, a
      dominant-negative regulator of E protein transcription factors, maintains HSC
      self-renewal by preserving the undifferentiated state. Id1-deficient HSCs show
      increased cell cycling, by BrdU incorporation in vivo, but fail to efficiently
      self-renew, leading to low steady-state HSC numbers and premature exhaustion in
      serial bone marrow transplant assays. The increased cycling reflects the
      perturbed differentiation process, because Id1 null HSCs more readily commit to
      myeloid differentiation, with inappropriate expression of myeloerythroid-specific
      genes. Thus, Id1 appears to regulate the fate of HSCs by acting as a true
      inhibitor of differentiation.

PMID- 17227851
TI  - Induction of inducible NO synthase in bystander human T cells increases
      allogeneic responses in the vasculature.
AB  - Inducible NO synthase (iNOS) in human T cells is implicated in the pathogenesis
      of graft arteriosclerosis. Here we analyze the regulation and role of iNOS in
      human peripheral blood T cells. Allogeneic endothelial cells (EC) or dermal
      fibroblasts induce iNOS mRNA and protein expression, as well as enzymatic
      activity in primary human CD8 T cells. Although human EC activate T cells through
      the presentation of alloantigen, iNOS induction is confined to nonactivated T
      cells and does not depend on MHC molecules or costimulators. iNOS induction does
      involve new transcription and depends on NF-kappaB. JAK signaling, initiated
      during T cell activation, inhibits iNOS expression. Even though iNOS is confined
      to bystander T cells, inhibition of iNOS activity reduces T cell proliferation in
      response to allogeneic EC, and addition of low levels of a NO donor rescues T
      cell responses. Similarly, iNOS is preferentially expressed by nonproliferating T
      cells within allografted arteries in vivo, and inhibition of iNOS activity
      reduces the number of activated T cells in these artery segments. These data
      identify a previously undescribed mechanism for enhanced activation of
      alloreactive T cells, namely stromal cell-mediated induction of iNOS in bystander
      T cells.

PMID- 17227852
TI  - The aryl hydrocarbon receptor is activated by modified low-density lipoprotein.
AB  - Endogenous activation of the aryl hydrocarbon receptor (AHR) is required for
      normal vascular development. This biology led us to investigate the interplay
      between the AHR and vascular physiology by using an in vitro model of fluid shear
      stress. Using this system, we show that fluid flow induces a robust AHR-mediated
      increase in CYP1 expression. Furthermore, we demonstrate that incubation with
      sheared bovine or human sera is sufficient for AHR activation, indicating that
      direct cellular exposure to shear stress is not required for this response.
      Fractionation of sera by size and density revealed the AHR-activating factor to
      be low-density lipoprotein (LDL). Purified LDL (0.1 mg/ml) from sheared sera
      induces a 6-fold increase in AHR-mediated signaling as compared with LDL purified
      from static sera. Similar results were obtained by exposing a purified fraction
      of LDL to fluid flow, suggesting that shear stress is capable of directly
      modifying LDL structure and/or function. In addition, we show that LDL can be
      converted to an AHR-activating species by conventional methods of lipoprotein
      modification, such as NaOCl oxidation. Finally, we demonstrate that an increased
      level of AHR-activating LDL is present in the sera of AHR null mice as compared
      with heterozygous littermates, suggesting a role for the Ahr locus in the
      physiological response to modified LDL in vivo. Overall, these data demonstrate a
      previously undescribed relationship between LDL modification and AHR biology and
      provide a potential explanation for the vascular abnormalities observed in AHR
      null mice.

PMID- 17227853
TI  - Transcriptional regulation of protein complexes within and across species.
AB  - Yeast two-hybrid and coimmunoprecipitation experiments have defined large-scale
      protein-protein interaction networks for many model species. Separately,
      systematic chromatin immunoprecipitation experiments have enabled the assembly of
      large networks of transcriptional regulatory interactions. To investigate the
      functional interplay between these two interaction types, we combined both within
      a probabilistic framework that models the cell as a network of transcription
      factors regulating protein complexes. This framework identified 72 putative
      coregulated complexes in yeast and allowed the prediction of 120 previously
      uncharacterized transcriptional interactions. Several predictions were tested by
      new microarray profiles, yielding a confirmation rate (58%) comparable with that
      of direct immunoprecipitation experiments. Furthermore, we extended our framework
      to a cross-species setting, identifying 24 coregulated complexes that were
      conserved between yeast and fly. Analyses of these conserved complexes revealed
      different conservation levels of their regulators and provided suggestive
      evidence that protein-protein interaction networks may evolve more slowly than
      transcriptional interaction networks. Our results demonstrate how multiple
      molecular interaction types can be integrated toward a global wiring diagram of
      the cell, and they provide insights into the evolutionary dynamics of protein
      complex regulation.

PMID- 17227854
TI  - Androgen receptor decoy molecules block the growth of prostate cancer.
AB  - The androgen receptor (AR) is activated by both ligand-dependent and -independent
      mechanisms. Current therapies for prostate cancer target the ligand-binding
      domain in the C terminus of the AR. However, ligand-independent activation of the
      AR occurs by the N-terminal domain (NTD), making the NTD a potential novel target
      for the treatment of hormone refractory prostate cancer. A possible therapeutic
      approach is to overexpress an AR NTD peptide to create decoy molecules that
      competitively bind the interacting proteins required for activation of the
      endogenous full-length AR. We provide evidence that in vivo expression of AR NTD
      decoys decreased tumor incidence and inhibited the growth of prostate cancer
      tumors. This growth inhibition was characterized by a 10-fold decrease in serum
      levels of prostate-specific antigen (PSA) (46.7 ng/ml+/-19.9 vs. 432.4 ng/ml+/
      201.3; P=0.0299) and a 4-fold decrease in tumor volume (92.2 mm3+/-43.4 vs. 331.4
      mm3+/-85.5; P=0.011). AR NTD decoy molecules also delayed hormonal progression,
      as determined by time to rising PSA levels after castration of the host. The
      tumors treated with AR NTD decoys contained more apoptotic cells and fewer
      proliferating cells, whereas no effect was seen on the viability of cells that
      did not depend on the AR. This work provides further evidence of the importance
      of the NTD of the AR in the progression of prostate cancer and presents a target
      for the development of antagonists of the AR in the clinical management of this
      disease.

PMID- 17227855
TI  - Decoding the neural substrates of reward-related decision making with functional
      MRI.
AB  - Although previous studies have implicated a diverse set of brain regions in
      reward-related decision making, it is not yet known which of these regions
      contain information that directly reflects a decision. Here, we measured brain
      activity using functional MRI in a group of subjects while they performed a
      simple reward-based decision-making task: probabilistic reversal-learning. We
      recorded brain activity from nine distinct regions of interest previously
      implicated in decision making and separated out local spatially distributed
      signals in each region from global differences in signal. Using a multivariate
      analysis approach, we determined the extent to which global and local signals
      could be used to decode subjects' subsequent behavioral choice, based on their
      brain activity on the preceding trial. We found that subjects' decisions could be
      decoded to a high level of accuracy on the basis of both local and global signals
      even before they were required to make a choice, and even before they knew which
      physical action would be required. Furthermore, the combined signals from three
      specific brain areas (anterior cingulate cortex, medial prefrontal cortex, and
      ventral striatum) were found to provide all of the information sufficient to
      decode subjects' decisions out of all of the regions we studied. These findings
      implicate a specific network of regions in encoding information relevant to
      subsequent behavioral choice.

PMID- 17227856
TI  - RNA expression in a cartilaginous fish cell line reveals ancient 3' noncoding
      regions highly conserved in vertebrates.
AB  - We have established a cartilaginous fish cell line [Squalus acanthias embryo cell
      line (SAE)], a mesenchymal stem cell line derived from the embryo of an
      elasmobranch, the spiny dogfish shark S. acanthias. Elasmobranchs (sharks and
      rays) first appeared >400 million years ago, and existing species provide useful
      models for comparative vertebrate cell biology, physiology, and genomics.
      Comparative vertebrate genomics among evolutionarily distant organisms can
      provide sequence conservation information that facilitates identification of
      critical coding and noncoding regions. Although these genomic analyses are
      informative, experimental verification of functions of genomic sequences depends
      heavily on cell culture approaches. Using ESTs defining mRNAs derived from the
      SAE cell line, we identified lengthy and highly conserved gene-specific
      nucleotide sequences in the noncoding 3' UTRs of eight genes involved in the
      regulation of cell growth and proliferation. Conserved noncoding 3' mRNA regions
      detected by using the shark nucleotide sequences as a starting point were found
      in a range of other vertebrate orders, including bony fish, birds, amphibians,
      and mammals. Nucleotide identity of shark and human in these regions was
      remarkably well conserved. Our results indicate that highly conserved gene
      sequences dating from the appearance of jawed vertebrates and representing
      potential cis-regulatory elements can be identified through the use of
      cartilaginous fish as a baseline. Because the expression of genes in the SAE cell
      line was prerequisite for their identification, this cartilaginous fish culture
      system also provides a physiologically valid tool to test functional hypotheses
      on the role of these ancient conserved sequences in comparative cell biology.

PMID- 17227857
TI  - Structural analysis and dimerization potential of the human TAF5 subunit of
      TFIID.
AB  - TFIID is an essential factor required for RNA polymerase II transcription but
      remains poorly understood because of its intrinsic complexity. Human TAF5, a 100
      kDa subunit of general transcription factor TFIID, is an essential gene and plays
      a critical role in assembling the 1.2 MDa TFIID complex. We report here a
      structural analysis of the TAF5 protein. Our structure at 2.2-A resolution of the
      TAF5-NTD2 domain reveals an alpha-helical domain with distant structural
      similarity to RNA polymerase II CTD interacting factors. The TAF5-NTD2 domain
      contains several conserved clefts likely to be critical for TFIID complex
      assembly. Our biochemical analysis of the human TAF5 protein demonstrates the
      ability of the N-terminal half of the TAF5 gene to form a flexible, extended
      dimer, a key property required for the assembly of the TFIID complex.

PMID- 17227858
TI  - Sensory integration across space and in time for decision making in the
      somatosensory system of rodents.
AB  - Environment is represented in the brain by a neural code that is a result of the
      spatiotemporal pattern of incoming sensory information. Sensory neurons encode
      inputs across space and in time such that activity of a given cell inhibits the
      ability of near-simultaneously arriving sensory stimuli to excite the cell. At
      the behavioral level, consequences of such suppression are unknown. We
      investigated the contribution of spatially distributed, near-simultaneous sensory
      inputs to decision making in a whisker-dependent learning task. Mice learned the
      task with a single whisker or multiple whiskers alike. Both groups of mice had
      similar learning curves and final success rates. However, multiple-whisker
      animals had faster response times than single-whisker mice, requiring only about
      half the time to perform the task successfully. The results show that spatially
      distributed sensory inputs in a highly redundant sensory environment improve
      speed but not accuracy of the decisions made during simple sensory detection.
      Suppression of the near-simultaneous sensory inputs could, therefore, act to
      reduce the sensory redundancy.

PMID- 17227859
TI  - The hallmark of AGC kinase functional divergence is its C-terminal tail, a cis
      acting regulatory module.
AB  - The catalytic activities of eukaryotic protein kinases (EPKs) are regulated by
      movement of the C-helix, movement of the N and C lobes upon ATP binding, and
      movement of the activation loop upon phosphorylation. Statistical analysis of the
      selective constraints associated with AGC kinase functional divergence reveals
      conserved interactions between these regulatory regions and three regions of the
      C-terminal tail (C-tail): the N-lobe tether (NLT), the active-site tether (AST),
      and the C-lobe tether (CLT). The NLT serves as a docking site for an upstream
      kinase PDK1 and, upon activation, positions the C-helix within the ATP binding
      pocket. The AST directly interacts with the ATP binding pocket, and the CLT
      interacts with the interlobe linker and the alphaC-beta4 loop, which appears to
      serve as a hinge for C-helix movement. The C-tail is a hallmark of AGC functional
      divergence inasmuch as most of the conserved core residues that distinguish AGC
      kinases from other EPKs are associated with the NLT, AST, or CLT. Moreover,
      several AGC catalytic core conserved residues that interact with the C-tail
      strikingly diverge from the canonical residues observed at corresponding
      positions in nearly all other EPKs, suggesting that the catalytic core may have
      coevolved with the C-tail in AGC kinases. These observations, along with the fact
      that the C-tail is needed for catalytic activity suggests that the C-tail is a
      cis-acting regulatory module that can also serve as a regulatory "handle," to
      which trans-acting cellular components can bind to modulate activity.

PMID- 17227860
TI  - Activity-based probes for proteomic profiling of histone deacetylase complexes.
AB  - Histone deacetylases (HDACs) are key regulators of gene expression that require
      assembly into larger protein complexes for activity. Efforts to understand how
      associated proteins modulate the function of HDACs would benefit from new
      technologies that evaluate HDAC activity in native biological systems. Here, we
      describe an active site-directed chemical probe for profiling HDACs in native
      proteomes and live cells. This probe, designated SAHA-BPyne, contains structural
      elements of the general HDAC inhibitor suberoylanilide hydroxamic acid (SAHA), as
      well as benzophenone and alkyne moieties to effect covalent modification and
      enrichment of HDACs, respectively. Both class I and II HDACs were identified as
      specific targets of SAHA-BPyne in proteomes. Interestingly, multiple HDAC
      associated proteins were also enriched by SAHA-BPyne, even after denaturation of
      probe-labeled proteomes. These data indicate that certain HDAC-associated
      proteins are directly modified by SAHA-BPyne, placing them in close proximity to
      HDAC active sites where they would be primed to regulate substrate recognition
      and activity. We further show that SAHA-BPyne can be used to measure differences
      in HDAC content and complex assembly in human disease models. This chemical
      proteomics probe should thus prove valuable for profiling both the activity state
      of HDACs and the binding proteins that regulate their function.

PMID- 17227861
TI  - A trap-and-release integrated microfluidic system for dynamic microarray
      applications.
AB  - Dynamic microarrays hold great promise for advancing research in proteomics,
      diagnostics and drug discovery. However, this potential has yet to be fully
      realized due to the lack of reliable multifunctional platforms to transport and
      immobilize particles, infuse reagents, observe the reaction, and retrieve
      selected particles. We achieved all these functions in a single integrated device
      through the combination of hydrodynamic and optical approaches. Hydrodynamic
      forces allow simultaneous transportation and immobilization of large number of
      particles, whereas optical-based microbubble technique for bead retrieval gives
      dexterity in handling individual particles without complicated circuitry. Based
      on the criterion derived in this paper, the device was designed, and fabricated
      using standard photolithography and soft lithography methods. We examined the
      dynamics of bubble formation and dissipation in the device, and parametric
      studies revealed that higher power settings at short intervals were more
      efficient than low power settings at longer intervals for bead retrieval. We also
      demonstrated the capabilities of our device and its potential as a tool for
      screening methods such as the "one-bead-one-compound" (OBOC) combinatorial
      library method. Although both approaches, hydrodynamic confinement and optical
      based microbubbles, are presented in one device, they can also be separately used
      for other applications in microchip devices.

PMID- 17227862
TI  - Wrath of the wraiths of CatSper3 and CatSper4.

PMID- 17227863
TI  - Pestera cu Oase 2 and the cranial morphology of early modern Europeans.
AB  - Between 2003 and 2005, the Pestera cu Oase, Romania yielded a largely complete
      early modern human cranium, Oase 2, scattered on the surface of a Late
      Pleistocene hydraulically displaced bone bed containing principally the remains
      of Ursus spelaeus. Multiple lines of evidence indicate an age of approximately
      40.5 thousand calendar years before the present (approximately 35 ka 14C B.P.).
      Morphological comparison of the adolescent Oase 2 cranium to relevant Late
      Pleistocene human samples documents a suite of derived modern human and/or non
      Neandertal features, including absence of a supraorbital torus, subrectangular
      orbits, prominent canine fossae, narrow nasal aperture, level nasal floor, angled
      and anteriorly oriented zygomatic bones, a high neurocranium with prominent
      parietal bosses and marked sagittal parietal curvature, superiorly positioned
      temporal zygomatic root, vertical auditory porous, laterally bulbous mastoid
      processes, superiorly positioned posterior semicircular canal, absence of a
      nuchal torus and a suprainiac fossa, and a small occipital bun. However, these
      features are associated with an exceptionally flat frontal arc, a moderately
      large juxtamastoid eminence, extremely large molars that become progressively
      larger distally, complex occlusal morphology of the upper third molar, and
      relatively anteriorly positioned zygomatic arches. Moreover, the featureless
      occipital region and small mastoid process are at variance with the large facial
      skeleton and dentition. This unusual mosaic in Oase 2, some of which is
      paralleled in the Oase 1 mandible, indicates both complex population dynamics as
      modern humans dispersed into Europe and significant ongoing human evolution once
      modern humans were established within Europe.

PMID- 17227864
TI  - Explicit off-line criteria for stable accurate time filtering of strongly
      unstable spatially extended systems.
AB  - Many contemporary problems in science involve making predictions based on partial
      observation of extremely complicated spatially extended systems with many degrees
      of freedom and physical instabilities on both large and small scales. Various new
      ensemble filtering strategies have been developed recently for these
      applications, and new mathematical issues arise. Here, explicit off-line test
      criteria for stable accurate discrete filtering are developed for use in the
      above context and mimic the classical stability analysis for finite difference
      schemes. First, constant coefficient partial differential equations, which are
      randomly forced and damped to mimic mesh scale energy spectra in the above
      problems are developed as off-line filtering test problems. Then mathematical
      analysis is used to show that under natural suitable hypothesis the time
      filtering algorithms for general finite difference discrete approximations to an
      sxs partial differential equation system with suitable observations decompose
      into much simpler independent s-dimensional filtering problems for each spatial
      wave number separately; in other test problems, such block diagonal models
      rigorously provide upper and lower bounds on the filtering algorithm. In this
      fashion, elementary off-line filtering criteria can be developed for complex
      spatially extended systems. The theory is illustrated for time filters by using
      both unstable and implicit difference scheme approximations to the stochastically
      forced heat equation where the combined effects of filter stability and model
      error are analyzed through the simpler off-line criteria.

PMID- 17227865
TI  - Histoplasma capsulatum alpha-(1,3)-glucan blocks innate immune recognition by the
      beta-glucan receptor.
AB  - Successful infection by fungal pathogens depends on subversion of host immune
      mechanisms that detect conserved cell wall components such as beta-glucans. A
      less common polysaccharide, alpha-(1,3)-glucan, is a cell wall constituent of
      most fungal respiratory pathogens and has been correlated with pathogenicity or
      linked directly to virulence. However, the precise mechanism by which alpha-(1,3)
      glucan promotes fungal virulence is unknown. Here, we show that alpha-(1,3)
      glucan is present in the outermost layer of the Histoplasma capsulatum yeast cell
      wall and contributes to pathogenesis by concealing immunostimulatory beta-glucans
      from detection by host phagocytic cells. Production of proinflammatory TNFalpha
      by phagocytes was suppressed either by the presence of the alpha-(1,3)-glucan
      layer on yeast cells or by RNA interference based depletion of the host beta
      glucan receptor dectin-1. Thus, we have functionally defined key molecular
      components influencing the initial host-pathogen interaction in histoplasmosis
      and have revealed an important mechanism by which H. capsulatum thwarts the host
      immune system. Furthermore, we propose that the degree of this evasion
      contributes to the difference in pathogenic potential between dimorphic fungal
      pathogens and opportunistic fungi.

PMID- 17227866
TI  - IFN-stimulated gene 15 functions as a critical antiviral molecule against
      influenza, herpes, and Sindbis viruses.
AB  - Type I interferons (IFNs) play an essential role in the host response to viral
      infection through the induction of numerous IFN-stimulated genes (ISGs),
      including important antiviral molecules such as PKR, RNase L, Mx, and iNOS. Yet,
      additional antiviral ISGs likely exist. IFN-stimulated gene 15 (ISG15) is a
      ubiquitin homolog that is rapidly up-regulated after viral infection, and it
      conjugates to a wide array of host proteins. Although it has been hypothesized
      that ISG15 functions as an antiviral molecule, the initial evaluation of ISG15
      deficient mice revealed no defects in their responses to vesicular stomatitis
      virus or lymphocytic choriomeningitis virus, leaving open the important question
      of whether ISG15 is an antiviral molecule in vivo. Here we demonstrate that ISG15
      is critical for the host response to viral infection. ISG15-/- mice are more
      susceptible to influenza A/WSN/33 and influenza B/Lee/40 virus infections. ISG15
      /- mice also exhibited increased susceptibility to both herpes simplex virus type
      1 and murine gammaherpesvirus 68 infection and to Sindbis virus infection. The
      increased susceptibility of ISG15-/- mice to Sindbis virus infection was rescued
      by expressing wild-type ISG15, but not a mutant form of ISG15 that cannot form
      conjugates, from the Sindbis virus genome. The demonstration of ISG15 as a novel
      antiviral molecule with activity against both RNA and DNA viruses provides a
      target for the development of therapies against important human pathogens.

PMID- 17227867
TI  - Restoration of connexin26 protein level in the cochlea completely rescues hearing
      in a mouse model of human connexin30-linked deafness.
AB  - Mutations in genes coding for connexin26 (Cx26) and/or Cx30 are linked to
      approximately half of all cases of human autosomal nonsyndromic prelingual
      deafness. Cx26 and Cx30 are the two major Cx isoforms found in the cochlea, and
      they coassemble to form hybrid (heteromeric and heterotypic) gap junctions (GJs).
      This molecular arrangement implies that homomeric GJs would remain in the cochlea
      if one of the coassembly partners were mutated resulting in null expression. We
      generated mice in which extra copies of the Cx26 gene were transgenically
      expressed from a modified bacterial artificial chromosome in a Cx30-/-
      background. In the absence of the Cx30 gene, Cx26 expressed from extra alleles
      completely restored hearing sensitivity and prevented hair cell death in deaf
      Cx30-/- mice. The results indicated that hybrid GJs consisting of Cx26 and Cx30
      were not essential for normal hearing in mice and suggested that up-regulation of
      Cx26 or slowing down its protein degradation might be a therapeutic strategy to
      prevent and treat deafness caused by Cx30 mutations.

PMID- 17227868
TI  - Alterations of cellular bioenergetics in pulmonary artery endothelial cells.
AB  - Idiopathic pulmonary arterial hypertension (IPAH) is pathogenetically related to
      low levels of the vasodilator nitric oxide (NO). Because NO regulates cellular
      respiration and mitochondrial biogenesis, we hypothesized that abnormalities of
      bioenergetics may be present in IPAH. Evaluation of pulmonary artery endothelial
      cells from IPAH and control lungs in vitro revealed that oxygen consumption of
      IPAH cells was decreased, especially in state 3 respiration with substrates
      glutamate-malate or succinate, and this decrease paralleled reduction in Complex
      IV activity and IPAH cellular NO synthesis. IPAH pulmonary artery endothelial
      cells had decreased mitochondrial dehydrogenase activity and lowered
      mitochondrial numbers per cell and mitochondrial DNA content, all of which
      increased after exposure to NO donors. Although IPAH/pulmonary artery endothelial
      cells' ATP content was similar to control under normoxia, cellular ATP did not
      change significantly in IPAH cells under hypoxia, whereas ATP decreased 35% in
      control cells, identifying a greater dependence on cellular respiration for
      energy in control cells. Evidence that glucose metabolism was subserving the
      primary role for energy requirements of IPAH cells was provided by the
      approximately 3-fold greater glycolytic rate of IPAH cells. Positron emission
      tomography scan with [18F]fluoro-deoxy-D-glucose performed on IPAH patients and
      healthy controls revealed significantly higher uptake in IPAH lungs as compared
      with controls, confirming that the glycolytic rate was increased in vivo. Thus,
      there are substantial changes in bioenergetics of IPAH endothelial cells, which
      may have consequences for pulmonary hypertensive responses and potentially in
      development of novel imaging modalities for diagnosis and evaluation of
      treatment.

PMID- 17227869
TI  - Cdc42 GTPase-activating protein deficiency promotes genomic instability and
      premature aging-like phenotypes.
AB  - Cdc42 is a member of the Rho GTPase family known to regulate cell actin
      cytoskeleton organization, polarity, and growth, but its function in mammalian
      organismal physiology remains unclear. We found that natural aging of WT mice is
      marked with increased Cdc42 activity in various tissues. Among the negative
      regulators of Cdc42, gene targeting of Cdc42 GTPase-activating protein (Cdc42GAP)
      results in constitutively elevated Cdc42-GTP level in diverse tissues of adult
      mice; significantly shortened life span of the animals; and multiple premature
      aging-like phenotypes, including a reduction in body mass, a loss of subdermal
      adipose tissue, severe lordokyphosis, muscle atrophy, osteoporosis, and reduction
      of reepithelialization ability in wound-healing. Cdc42GAP-/- mouse embryonic
      fibroblasts and/or tissues display reduced population doubling, significantly
      dampened DNA damage repair activity after DNA-damaging agent treatment,
      accumulated genomic abnormalities, and induction of p53, p16Ink4a, p21Cip1, and
      senescence-associated beta-galactosidase expressions. Furthermore, Cdc42
      activation is sufficient to promote a premature cellular senescence phenotype
      that depends on p53. These results suggest a role of Cdc42 activity in regulating
      mammalian genomic stability and aging-related physiology.

PMID- 17227871
TI  - Barriers and strategies to influencing physician behavior.

PMID- 17227870
TI  - Progressive parkinsonism in mice with respiratory-chain-deficient dopamine
      neurons.
AB  - Mitochondrial dysfunction is implicated in the pathophysiology of Parkinson's
      disease (PD), a common age-associated neurodegenerative disease characterized by
      intraneuronal inclusions (Lewy bodies) and progressive degeneration of the
      nigrostriatal dopamine (DA) system. It has recently been demonstrated that
      midbrain DA neurons of PD patients and elderly humans contain high levels of
      somatic mtDNA mutations, which may impair respiratory chain function. However,
      clinical studies have not established whether the respiratory chain deficiency is
      a primary abnormality leading to inclusion formation and DA neuron death, or
      whether generalized metabolic abnormalities within the degenerating DA neurons
      cause secondary damage to mitochondria. We have used a reverse genetic approach
      to investigate this question and created conditional knockout mice (termed
      MitoPark mice), with disruption of the gene for mitochondrial transcription
      factor A (Tfam) in DA neurons. The knockout mice have reduced mtDNA expression
      and respiratory chain deficiency in midbrain DA neurons, which, in turn, leads to
      a parkinsonism phenotype with adult onset of slowly progressive impairment of
      motor function accompanied by formation of intraneuronal inclusions and dopamine
      nerve cell death. Confocal and electron microscopy show that the inclusions
      contain both mitochondrial protein and membrane components. These experiments
      demonstrate that respiratory chain dysfunction in DA neurons may be of
      pathophysiological importance in PD.

PMID- 17227872
TI  - The Patient Safety and Quality Improvement Act of 2005: provisions and potential
      opportunities.

PMID- 17227873
TI  - Development and evaluation of a 1-day interclerkship program for medical students
      on medical errors and patient safety.
AB  - Medical students need to be well informed about medical errors and patient
      safety. Pursuant to a needs assessment and pilot program, 229 third-year students
      participated in a 1-day program on patient safety including a plenary session and
      workshops. Attitudes and beliefs were measured by a survey at the beginning and
      end of the program. Completed surveys were returned by 124 (54%) students. Their
      level of agreement with 14 of 21 rating scale items changed in the expected
      direction. There were 7 items in which the students' baseline responses were
      already positive and did not change significantly. A 1-day program on patient
      safety in the third year of medical school can change students' attitudes and
      beliefs. There may be a subset of students needing closer attention. The findings
      provide evidence for the validity of the attitude survey and reinforce the
      effectiveness of interclerkship programs in medical schools.

PMID- 17227874
TI  - The role of physicians and certification boards to improve quality.
AB  - Amid growing focus on individual physician performance, it is timely to examine
      what evidence exists that physicians can be facilitators and leaders for health
      care quality improvement in their local health care environments. Despite the
      importance of governmental policy and national initiatives, change in health care
      quality must occur in the context of local communities. Therefore, individual
      physician involvement, working with other local health care leaders and
      providers, will be crucial to future quality improvement. The objectives of this
      article are as follows: (1) outline why physicians must be involved in quality
      improvement, (2) delineate the barriers and facilitators to physician
      involvement, and (3) discuss how medical certification boards can facilitate
      greater physician involvement in quality improvement.

PMID- 17227875
TI  - Patient safety rounds: description of an inexpensive but important strategy to
      improve the safety culture.
AB  - Patient safety rounds (PSRs) were established at the University of Michigan
      Medical Center to improve patient safety by opening a new line of communication
      between the chief of staff and frontline caregivers. Patient safety rounds are
      biweekly, hour long meetings between the chief of staff and care givers on
      individual patient care units. In the past 4 years (2002 to 2006), 70 PSRs have
      been conducted, and more than 900 area staff members have participated. Staff
      attendance averages 8 to 10 unit or area staff members per session. Patient
      safety rounds have proven to be a concrete, inexpensive mechanism to enhance
      patient safety. Benefits have been documented in the improvement in the safety
      culture and development and implementation of preventive strategies to solve
      patient safety issues. Key components in the success of PSRs are active medical
      staff leadership and the engagement of physicians and senior management in the
      process improvements the PSRs have directed.

PMID- 17227876
TI  - Improving diabetes care through a multicomponent quality improvement model in a
      practice-based research network.
AB  - This article reports the impact of a multicomponent quality improvement
      intervention on adherence with 13 measures of diabetes care and a summary
      measure, the Diabetes Summary Quality Index (Diabetes-SQUID). The intervention
      was conducted between January 1, 2004, and July 1, 2005, within 66 primary care
      practices in 33 states, including 372 providers and 24 250 adult patients with
      diabetes. Across all practices, the average Diabetes-SQUID was 50.6% (10th
      percentile 36.5%, 90th percentile 63.0%) on January 1, 2004, and 58.4% (10th
      percentile 47.6%, 90th percentile 69.7%) on July 1, 2005, with an average
      absolute improvement of 7.8% (95% confidence interval, 5.9%-9.7%). Significant
      improvements occurred for 12 of the 13 individual measures: blood pressure and
      urine microalbumin monitoring; HDL cholesterol, LDL cholesterol, triglyceride,
      and glycosylated hemoglobin measurements; prescription of antiplatelet therapy;
      and blood pressure, HDL-cholesterol, LDL-cholesterol, triglyceride, and
      glycosylated hemoglobin control. The findings suggest that a multicomponent
      intervention can have a robust impact on quality of care for diabetes.

PMID- 17227877
TI  - Patient satisfaction, self-rated health status, and health confidence: an
      assessment of the utility of single-item questions.
AB  - This study examined if known predictors of patient satisfaction would still be
      significant when single items are used. Approximately 5000 elderly persons were
      randomly sampled from 65 000 households in West Texas. Single-item questions
      about patient satisfaction, self-rated overall health status, self-rated mental
      health, and health confidence were analyzed by chi-square tests and logistic
      regressions. Slightly more than 12% of the participants were not satisfied or
      barely satisfied with health care received. Those who reported higher health
      confidence, lower self-rated overall health, having emotional problems, or who
      were men were less likely to be satisfied with health care. A simple survey tool
      based on single-item questions identified by the current study might be useful
      for monitoring patient satisfaction, self-rated health, and health confidence in
      primary care settings and hence might assist management in capturing the basic
      picture for improving health care quality.

PMID- 17227878
TI  - The concept of reliability in emergency medicine.
AB  - Despite the fact that the United States boasts one of the most advanced health
      care systems in the world, this system is highly "unreliable" and fraught with
      error. This article is an introduction to the concept of "reliability" in
      emergency medicine. It suggests ways in which the health care system could
      promote increased reliability of operations and processes in the emergency
      department by using reliability principles and tools that have proven successful
      in other high-risk settings. Through comparisons to aviation and nuclear power,
      this article illustrates the differences in culture between emergency medicine
      and other high-risk organizations and points to the qualities that promote
      reliability. Finally, a specific model for reliability in the emergency
      department, operations, and clinical processes is proposed.

PMID- 17227880
TI  - A classification scheme for redox-based modifications of proteins.

PMID- 17227879
TI  - Emergency departments in crisis: implications for accessibility, quality, and
      safety.

PMID- 17227881
TI  - Heme oxygenase-1: a multifaceted triple-threat molecule.

PMID- 17227882
TI  - Follicle-stimulating hormone-induced activation of Gata4 contributes in the up
      regulation of Cyp19 expression in rat granulosa cells.
AB  - Several studies have suggested that the transcription factor GATA4 plays an
      important role in ovarian function. This study evaluated the effects of GATA4 on
      the regulation of the Cyp19 gene in primary rat granulosa cells under basal
      conditions and in response to stimulation by FSH. A significant increase in GATA4
      mRNA, protein, and DNA binding activity was observed in rats treated with
      pregnant mare serum gonadotropin, a hormone that binds to the FSH receptors, and
      in granulosa cells incubated with FSH. Enrichment of the Cyp19 promoter was
      observed in granulosa cells treated with FSH after chromatin precipitation with
      an anti-GATA4 antibody. Mutation of the GATA binding site on the Cyp19 promoter
      and inhibition of GATA4 expression with specific small interfering RNA
      significantly reduced FSH-enhanced Cyp19 expression, whereas overexpression of
      GATA4 increased Cyp19 promoter activity. A synergistic effect observed between
      GATA4 overexpression and FSH treatment in Cyp19 expression was abolished by
      mutating Ser105 in the GATA4 protein or by pretreating granulosa cells with a
      protein kinase A inhibitor. Inhibition of phosphatidylinositol-dependent kinase
      (PI3-K)/casein kinase 2 or ERK1/2 attenuated GATA4/FSH synergism, whereas the
      simultaneous blockade of PI3-K/casein kinase 2 and ERK1/2 activity eliminated
      Cyp19 stimulation. Finally, we demonstrated that FSH increases GATA4
      phosphorylation and that GATA4 activation requires the activation of multiple
      kinases, including ERK1/2, PI3-K, and protein kinase A. These findings
      demonstrate that GATA4 contributes in the regulation of Cyp19 expression in the
      rat ovary and provide the first evidence that FSH regulates GATA4 activity.

PMID- 17227883
TI  - Altered promoter recycling rates contribute to dominant-negative activity of
      human peroxisome proliferator-activated receptor-gamma mutations associated with
      diabetes.
AB  - The transcription factor peroxisome proliferator-activated receptor-gamma
      (PPARgamma) plays an important role in regulating lipid and glucose metabolism
      and improves insulin sensitivity in diabetic patients when activated by
      thiazolidinedione drugs. Several loss-of-function mutations in PPARgamma have
      been identified that cause lipodystrophy and diabetes in humans. Because affected
      individuals are heterozygotes and have one normal PPARgamma allele, it is of
      interest to know whether these mutations act in a dominant-negative fashion to
      inhibit the activity of the wild-type (WT) receptor. Here we compare the
      molecular phenotypes of two previously identified PPARgamma mutations: P467L,
      reported to be dominant negative; and F388L, reported to be devoid of dominant
      negative activity. We developed a competitive chromatin immunoprecipitation assay
      to measure the relative ability of mutant PPARgamma to compete with WT receptor
      for binding to a PPAR regulatory element (PPRE)-containing promoter. By
      determining the ratio of mutant and WT receptors bound to a PPRE over time, we
      estimated the relative promoter turnover rate of each receptor. This assay
      demonstrated that PPARgamma bearing the P467L had a reduced promoter turnover
      rate compared with the F388L receptor, and over time out-competed the WT receptor
      for promoter binding sites. We propose that the P467L receptor is dominant
      negative because in a cell containing both WT and mutant receptors, the majority
      of the PPAR-regulated promoters will be occupied by the transcriptionally
      defective mutant receptor. In contrast, the F388L mutation lacks dominant
      negative activity because its more rapid promoter turnover rate prevented it from
      out-competing the WT receptor for promoter binding sites.

PMID- 17227884
TI  - Dynamic histone acetylation/deacetylation with progesterone receptor-mediated
      transcription.
AB  - Histone acetylation is a highly dynamic posttranslational modification that plays
      an important role in gene expression. Previous work showed that promoter histone
      deacetylation is accompanied by progesterone receptor (PR)-mediated activation of
      the mouse mammary tumor virus (MMTV) promoter. We investigated the role of this
      deacetylation and found that this histone deacetylation is not a singular event.
      In fact, histone acetylation at the MMTV promoter is highly dynamic, with an
      initial increase in acetylation followed by an eventual net deacetylation of
      histone H4. The timing of increase in acetylation of H4 coincides with the time
      at which PR, RNA polymerase II, and histone acetyltransferases cAMP response
      element-binding protein (CREB)-binding protein and p300 are recruited to the MMTV
      promoter. The timing in which histone H4 deacetylation occurs (after PR and RNA
      polymerase II recruitment) and the limited effect that trichostatin A and small
      interfering RNA knockdown of histone deacetylase (HDAC)3 have on MMTV
      transcription suggests that this deacetylation activity is not required for the
      initiation of PR-mediated transcription. Interestingly, two HDACs, HDAC1 and
      HDAC3, are already present at the MMTV before transcription activation. HDAC
      association at the MMTV promoter fluctuates during the hormone treatment. In
      particular, HDAC3 is temporarily undetected at the MMTV promoter within minutes
      after hormone treatment when the histone H4 acetylation increases but returns to
      the promoter near the time when histone acetylation levels start to decline.
      These results demonstrate the dynamic nature of coactivator/corepressor-promoter
      association and histone modifications such as acetylation during a transcription
      activation event.

PMID- 17227887
TI  - Evolution and structural diversification of hyperpolarization-activated cyclic
      nucleotide-gated channel genes.
AB  - Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are members of
      the voltage-gated channel superfamily and play a critical role in cellular pace
      making. Overall sequence conservation is high throughout the family, and channel
      functions are similar but not identical. Phylogenetic analyses are imperative to
      understand how these genes have evolved and to make informed comparisons of HCN
      structure and function. These have been previously limited, however, by the small
      number of available sequences, from a minimal number of species unevenly
      distributed over evolutionary time. We have now identified and annotated 31 novel
      genes from invertebrates, urochordates, fish, amphibians, birds, and mammals.
      With increased sequence numbers and a broader species representation, a more
      precise sequence comparison was performed and an evolutionary history for these
      genes was constructed. Our data confirm the existence of at least four vertebrate
      paralogs and suggest that these arose via three duplication and diversification
      events from a single ancestral gene. Additional lineage-specific duplications
      appear to have occurred in urochordate and fish genomes. Based on exon boundary
      conservation and phylogenetic analyses, we hypothesize that mammalian gene
      structure was established, and duplication events occurred, after the divergence
      of urochordates and before the divergence of fish from the tetrapod lineage. In
      addition, we identified highly conserved sequence regions that are likely
      important for general HCN functions, as well as regions with differences
      conserved among each of the individual paralogs. The latter may underlie more
      subtle isoform-specific properties that are otherwise masked by the high identity
      among mammalian orthologs and/or inaccurate alignments between paralogs.

PMID- 17227886
TI  - Loss of testicular orphan receptor 4 impairs normal myelination in mouse
      forebrain.
AB  - Testicular orphan nuclear receptor 4 (TR4) has been suggested to play important
      roles in the development and functioning of the central nervous system (CNS). We
      find reduced myelination in TR4 knockout (TR4(-/-)) mice, which is particularly
      obvious in forebrains and in early developmental stages. Further analysis reveals
      that CC-1-positive (CC-1+) oligodendrocytes are decreased in TR4(-/-) forebrains.
      The O4+ signals are also reduced in TR4(-/-) forebrains when examined at
      postnatal d 7. However, the number and proliferation rate of platelet-derived
      growth factor receptor alpha-positive (PDGFalphaR+) oligodendrocyte precursor
      cells (OPCs) remain unaffected in these regions, suggesting that loss of TR4
      interrupts oligodendrocyte differentiation. This is further supported by the
      observation that CC-1+ oligodendrocytes derived from 5-bromo-2'-deoxyuridine
      incorporating OPCs are significantly reduced in TR4(-/-) forebrains. We also find
      higher Jagged1 expression levels in axon fiber-enriched regions in TR4(-/-)
      forebrains, suggesting a more activated Notch signaling in these regions that
      correlates with previous reports showing that Notch activation inhibits
      oligodendrocyte differentiation. Together, our results suggest that TR4 is
      required for proper myelination in the CNS and is particularly important for
      oligodendrocyte differentiation and maturation in the forebrain regions. The
      altered Jagged1-Notch signaling in TR4(-/-) forebrain underlies a potential
      mechanism that contributes to the reduced myelination in the forebrain.

PMID- 17227888
TI  - Fast skeletal muscle myosin heavy chain gene cluster of medaka Oryzias latipes
      enrolled in temperature adaptation.
AB  - To disclose mechanisms involved in temperature acclimation of fish muscle, we
      subjected eurythermal fish of medaka Oryzias latipes to cloning of myosin heavy
      chain genes (MYHs). We cloned cDNAs encoding fast skeletal muscle myosin heavy
      chain (MYH) isoforms from cDNA libraries of medaka acclimated to 10 and 30
      degrees C and observed that different MYH cDNA clones are expressed in the two
      temperature-acclimated fish. Subsequently, we isolated several overlapping MYH
      contigs by shotgun cloning strategy from a medaka genomic library. Contig
      assembly of the complete medaka MYH (mMYH) locus of 219 kbp revealed a cluster of
      tandemly arrayed 11 mMYHs, in which eight genes are actually transcribed, with
      the remaining three being pseudogenes. Expression analysis of the transcribed
      genes revealed that two genes were each highly expressed in medaka acclimated to
      10 and 30 degrees C, whereas comparatively lower expression levels of the three
      genes were exclusively observed in medaka acclimated to 30 degrees C. cDNAs of
      the remaining genes were too underrepresented in the libraries to determine the
      expression levels, and the transcripts could only be obtained by reverse
      transcription-polymerase chain reaction. Deduced amino acid sequences in the loop
      1 and loop 2 regions of mMYHs were highly variable, suggesting that these
      isoforms were functionally different. The present findings consolidate our
      knowledge on teleost MYH multigene family and would provide further insight into
      the mechanisms by which expressions of individual MYH molecules are fine-tuned
      with environmental temperature fluctuations with further functional analysis of
      the genes concerned.

PMID- 17227889
TI  - Desmoplakin: an unexpected regulator of microtubule organization in the
      epidermis.
AB  - Despite their importance in cell shape and polarity generation, the organization
      of microtubules in differentiated cells and tissues remains relatively unexplored
      in mammals. We generated transgenic mice in which the epidermis expresses a
      fluorescently labeled microtubule-binding protein and show that in epidermis and
      in cultured keratinocytes, microtubules stereotypically reorganize as they
      differentiate. In basal cells, microtubules form a cytoplasmic network emanating
      from an apical centrosome. In suprabasal cells, microtubules concentrate at cell
      cell junctions. The centrosome retains its ability to nucleate microtubules in
      differentiated cells, but no longer anchors them. During epidermal
      differentiation, ninein, which is a centrosomal protein required for microtubule
      anchoring (Dammermann, A., and A. Merdes. 2002. J. Cell Biol. 159:255-266;
      Delgehyr, N., J. Sillibourne, and M. Bornens. 2005. J. Cell Sci. 118:1565-1575;
      Mogensen, M.M., A. Malik, M. Piel, V. Bouckson-Castaing, and M. Bornens. 2000. J.
      Cell Sci. 113:3013-3023), is lost from the centrosome and is recruited to
      desmosomes by desmoplakin (DP). Loss of DP prevents accumulation of cortical
      microtubules in vivo and in vitro. Our work uncovers a differentiation-specific
      rearrangement of the microtubule cytoskeleton in epidermis, and defines an
      essential role for DP in the process.

PMID- 17227890
TI  - Aberrant monomethylation of histone H4 lysine 20 activates the DNA damage
      checkpoint in Drosophila melanogaster.
AB  - PR-Set7 is a histone methyltransferase that specifically monomethylates histone
      H4 lysine 20 (K20) and is essential for cell proliferation. Our results show that
      in PR-Set7 mutants, the DNA damage checkpoint is activated. This phenotype is
      manifested by reduction in both the mitotic and the S phase indexes, a delay in
      the progression through early mitosis, and strong reduction of cyclin B.
      Furthermore, in a double mutant of PR-Set7 and mei-41 (the fly ATR orthologue),
      the abnormalities of mitotic progression and the cyclin B protein level were
      rescued. PR-Set7 also showed a defect in chromosome condensation that was
      enhanced in the double mutant. We therefore propose that monomethylated H4K20 is
      involved in the maintenance of proper higher order structure of DNA and is
      consequently essential for chromosome condensation.

PMID- 17227891
TI  - Nucleoplasmic LAP2alpha-lamin A complexes are required to maintain a
      proliferative state in human fibroblasts.
AB  - In human diploid fibroblasts (HDFs), expression of lamina-associated polypeptide
      2 alpha (LAP2alpha) upon entry and exit from G(0) is tightly correlated with
      phosphorylation and subnuclear localization of retinoblastoma protein (Rb).
      Phosphoisoforms of Rb and LAP2alpha are down-regulated in G(0). Although RbS780
      phosphoform and LAP2alpha are up-regulated upon reentry into G(1) and colocalize
      in the nucleoplasm, RbS795 migrates between nucleoplasmic and speckle
      compartments. In HDFs, which are null for lamins A/C, LAP2alpha is mislocalized
      within nuclear aggregates, and this is correlated with cell cycle arrest and
      accumulation of Rb within speckles. Nuclear retention of nucleoplasmic Rb during
      G(1) phase but not of speckle-associated Rb depends on lamin A/C. siRNA knock
      down of LAP2alpha or lamin A/C in HDFs leads to accumulation of Rb in speckles
      and G(1) arrest, probably because of activation of a cell cycle checkpoint. Our
      results suggest that LAP2alpha and lamin A/C are involved in controlling Rb
      localization and phosphorylation, and a lack or mislocalization of either protein
      leads to cell cycle arrest in HDFs.

PMID- 17227892
TI  - Cell cycle progression and de novo centriole assembly after centrosomal removal
      in untransformed human cells.
AB  - How centrosome removal or perturbations of centrosomal proteins leads to G1
      arrest in untransformed mammalian cells has been a mystery. We use microsurgery
      and laser ablation to remove the centrosome from two types of normal human cells.
      First, we find that the cells assemble centrioles de novo after centrosome
      removal; thus, this phenomenon is not restricted to transformed cells. Second,
      normal cells can progress through G1 in its entirety without centrioles.
      Therefore, the centrosome is not a necessary, integral part of the mechanisms
      that drive the cell cycle through G1 into S phase. Third, we provide evidence
      that centrosome loss is, functionally, a stress that can act additively with
      other stresses to arrest cells in G1 in a p38-dependent fashion.

PMID- 17227893
TI  - Loss of APC induces polyploidy as a result of a combination of defects in mitosis
      and apoptosis.
AB  - Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene initiate
      a majority of colorectal cancers. Acquisition of chromosomal instability is an
      early event in these tumors. We provide evidence that the loss of APC leads to a
      partial loss of interkinetochore tension at metaphase and alters mitotic
      progression. Furthermore, we show that inhibition of APC in U2OS cells
      compromises the mitotic spindle checkpoint. This is accompanied by a decrease in
      the association of the checkpoint proteins Bub1 and BubR1 with kinetochores.
      Additionally, APC depletion reduced apoptosis. As expected from this combination
      of defects, tetraploidy and polyploidy are consequences of APC inhibition in
      vitro and in vivo. The removal of APC produced the same defects in HCT116 cells
      that have constitutively active beta-catenin. These data show that the loss of
      APC immediately induces chromosomal instability as a result of a combination of
      mitotic and apoptotic defects. We suggest that these defects amplify each other
      to increase the incidence of tetra- and polyploidy in early stages of
      tumorigenesis.

PMID- 17227895
TI  - Intramolecular rearrangement of linolenate peroxyl radicals in lipoxygenase
      reactions at lower oxygen content.
AB  - Variation of tissue oxygen content is thought to be a possible factor in
      determining the structural diversity of hydroperoxy fatty acids. In the present
      study, we evaluated the structural diversity of intermediate carbon-centered
      radicals at lower oxygen content. When the buffered solution (pH 7.4) containing
      1.0 mM alpha-linolenic acid, 1.0 muM soybean 15-lipoxygenase, and 1.0 mM nitroxyl
      radical [3-carbamoyl-2,2,5,5-tetramethyl-3-pyrroline-N-oxyl (CmDeltaP)], which
      selectively traps carbon-centered radicals, was incubated in a sealed vial, the
      generation of linolenate hydroperoxide was completed within 1 min. In the
      subsequent reaction at lower oxygen content, the production of the [LnA-H+O(2)].
      CmDeltaP adduct was ascertained by liquid chromatography tandem mass spectrometry
      with precursor ion scanning. Furthermore, HPLC analysis with photodiode array
      detection showed that the adduct exhibits an absorption maximum at 278 nm,
      indicating a conjugated triene moiety. On the basis of these facts, the structure
      of the adduct was speculated to be C(2)H(5)-CH(CmDeltaP)-CH = CH-CH = CH-CH = CH
      CH(OOH) -C(7)H(14)-COOH. We proposed a possible reaction pathway as follows: a
      linolenate 9-peroxyl radical generated in the lipoxygenase reaction might be
      converted into C(2)H(5)-.CH-CH = CH-CH = CH-CH = CH-CH(OOH) -C(7)H(14)-COOH
      through an intramolecular rearrangement. This intermediate radical may give rise
      to hydroperoxy fatty acids with structural diversity.

PMID- 17227894
TI  - Involvement of zebrafish Na+,K+ ATPase in myocardial cell junction maintenance.
AB  - Na(+),K(+) ATPase is an essential ion pump involved in regulating ionic
      concentrations within epithelial cells. The zebrafish heart and mind (had)
      mutation, which disrupts the alpha1B1 subunit of Na(+),K(+) ATPase, causes heart
      tube elongation defects and other developmental abnormalities that are
      reminiscent of several epithelial cell polarity mutants, including nagie oko
      (nok). We demonstrate genetic interactions between had and nok in maintaining
      Zonula occludens-1 (ZO-1)-positive junction belts within myocardial cells.
      Functional tests and pharmacological inhibition experiments demonstrate that
      Na(+),K(+) ATPase activity is positively regulated via an N-terminal
      phosphorylation site that is necessary for correct heart morphogenesis to occur,
      and that maintenance of ZO-1 junction belts requires ion pump activity. These
      findings suggest that the correct ionic balance of myocardial cells is essential
      for the maintenance of epithelial integrity during heart morphogenesis.

PMID- 17227896
TI  - Minimally invasive approaches for diagnosis and treatment of early-stage breast
      cancer.
AB  - Breast cancer management has been evolving toward minimally invasive approaches.
      Image-guided percutaneous biopsy techniques provide accurate histologic diagnosis
      without the need for surgical biopsy. Breast conservation therapy has become the
      treatment standard for early-stage breast cancer. Sentinel lymph node biopsy is a
      new procedure that can predict axillary lymph node status without the need of
      axillary lymph node dissection. The next challenge is to treat primary tumors
      without surgery. For this purpose, several new minimally invasive procedures,
      including radiofrequency ablation, interstitial laser ablation, focused
      ultrasound ablation, and cryotherapy, are currently under development and may
      offer effective tumor management and provide treatment options that are
      psychologically and cosmetically more acceptable to the patients than are
      traditional surgical therapies. In this review, we give an overview of minimally
      invasive approaches for the diagnostic and therapeutic management of early-stage
      breast cancer.

PMID- 17227897
TI  - Disseminated malignancy misdiagnosed as thrombotic thrombocytopenic purpura: A
      report of 10 patients and a systematic review of published cases.
AB  - BACKGROUND: Patients with disseminated malignancy who present with
      microangiopathic hemolytic anemia and thrombocytopenia may be misdiagnosed as
      thrombotic thrombocytopenic purpura (TTP), resulting in inappropriate plasma
      exchange treatment, a procedure with major risk, and delay of appropriate
      chemotherapy. PURPOSE: To assess clinical features that may distinguish occult
      disseminated malignancy from TTP. PATIENTS AND METHODS: We report the 17-year
      experience of The Oklahoma TTP-Hemolytic-Uremic Syndrome (HUS) Registry (1989
      2005) and a systematic review of previously published case reports. RESULTS: Ten
      of 351 patients in the Oklahoma Registry who were initially diagnosed with TTP
      and treated with plasma exchange were subsequently discovered to have
      disseminated malignancy. Only one patient had a history of cancer. In these 10
      patients, neurologic abnormalities, hematocrit, platelet count, and serum
      creatinine were not different from the 133 concurrent patients with idiopathic
      TTP. Patients with disseminated malignancy had a longer duration of symptoms,
      more frequent presence of respiratory symptoms, higher lactate dehydrogenase
      levels, and more often failed to respond to plasma exchange treatment. Diagnosis
      of malignancy was made by bone marrow biopsy in six patients but not until
      autopsy in two patients. A systematic literature review identified 19 additional
      patients, reported from 1965 to 2005, in whom TTP or HUS was initially suspected
      and systemic malignancy was subsequently discovered. Fourteen different malignant
      disorders were diagnosed in these 29 patients. CONCLUSIONS: Occult disseminated
      malignancy may mimic TTP. A search for systemic malignancy, including a bone
      marrow biopsy, is appropriate when patients with TTP have atypical clinical
      features or fail to respond to plasma exchange.

PMID- 17227898
TI  - Cancer statistics, trends, and multiple primary cancer analyses from the
      Surveillance, Epidemiology, and End Results (SEER) Program.
AB  - An overview of cancer statistics and trends for selected cancers and all sites
      combined are given based on data from the Surveillance, Epidemiology, and End
      Results Program. Median age at diagnosis for all sites combined shows a 2-year
      increase from 1974 through 1978 to 1999 through 2003. Changes in cancer incidence
      rates from 1975 through 2003 are summarized by annual percent change for time
      periods determined by joinpoint regression analysis. After initial stability
      (1975-1979), incidence rates in women for all cancer sites combined increased
      from 1979 through 2003, although the rate of increase has recently slowed. For
      men, initial increases in all cancer sites combined (1975-1992) are followed by
      decreasing incidence rates (1992-1995) and stable trends from 1995 through 2003.
      Female thyroid cancer shows continued increasing incidence rates from 1981
      through 2003. Blacks have the highest incidence and mortality rates for men and
      women for all cancer sites combined. Based on 2001 through 2003 data, the
      likelihood of developing cancer during one's lifetime is approximately one in two
      for men and one in three for women. Five-year relative survival for all stages
      combined (1996-2002) ranges from 16% for lung to 100% for prostate cancer
      patients. Cancer survival varies by stage of disease and race, with lower
      survival in blacks compared with whites. The risk of developing subsequent
      multiple primary cancers varies from 1% for an initial liver primary diagnosis to
      16% for initial bladder cancer primaries. The impact on the future U.S. cancer
      burden is estimated based on the growing and aging U.S. population. The number of
      new cancer patients is expected to more than double from 1.36 million in 2000 to
      almost 3.0 million in 2050.

PMID- 17227899
TI  - The continuum of care: a paradigm for the management of metastatic colorectal
      cancer.
AB  - New agents for the treatment of metastatic colorectal cancer have extended median
      overall survival to more than 20 months, an increase that has changed the view of
      advanced colorectal cancer from an acute to a chronic condition. This article
      proposes a shift in treatment strategy from the concept of successive "lines" of
      therapy, in which chemotherapy is continued until disease progression, to that of
      a continuum of care, in which the use of chemotherapy is tailored to the clinical
      setting and includes switching chemotherapy prior to disease progression,
      maintenance therapy, drug "holidays," and surgical resection of metastases in
      selected patients. In this approach, the distinction between lines of therapy is
      no longer absolute. This represents a paradigm shift in the management of
      metastatic colorectal cancer to that of a continuum of care approach that
      includes individualized planning, in which patients are given the opportunity to
      benefit from exposure to all active agents and modalities while minimizing
      unnecessary treatment and toxicity, with the ultimate goal of improving survival
      as well as quality of life.

PMID- 17227900
TI  - Management of recurrent testicular germ cell tumors.
AB  - Although front-line chemotherapy cures most men with testicular germ cell tumors,
      salvage therapy is still important in a small but significant minority. Second
      line conventional-dose or high-dose chemotherapy with stem cell rescue may cure
      25%-50% of patients. New chemotherapeutic agents, including the taxanes
      gemcitabine and oxaliplatin, have added to the therapeutic armamentarium. Salvage
      surgical resection has an important role in selected patients. Cisplatin
      refractory patients have a poor prognosis with current therapy, and novel
      chemotherapeutic and biologic agents need to be discovered for such patients.

PMID- 17227901
TI  - The use of bisphosphonates in elderly cancer patients.
AB  - As life expectancy increases throughout the 21st century, the size of the elderly
      population will also expand. This will have a marked effect on the number of
      patients with cancer who are classified as elderly. Despite this, the design of
      most clinical studies of cancer therapies excludes those patients who are > or
      =70 years of age. Bisphosphonates are an example of a cancer therapy that has not
      been examined in randomized clinical trials of elderly patients. These agents are
      used for the prevention of skeletal complications and the relief of bone pain in
      patients with bone metastases. When deciding which bisphosphonate to prescribe to
      an elderly patient, each drug should be considered on its individual merits.
      Examples of areas of concern with bisphosphonates in elderly patients include
      their relative renal safety profiles and propensity for osteonecrosis of the jaw.
      Another consideration when choosing the most appropriate formulation is the
      preferred method of administration (oral or i.v.), which may affect patient
      compliance with therapy. As the use of bisphosphonates increases, the need for
      data on their use in elderly patients also becomes greater. Clinical trials of
      bisphosphonates in this patient population are currently under way, and their
      results are keenly awaited.

PMID- 17227902
TI  - Early changes in CA125 after treatment with pegylated liposomal doxorubicin or
      topotecan do not always reflect best response in recurrent ovarian cancer
      patients.
AB  - PURPOSE: To examine early changes in CA125 relative to objective response in
      patients with recurrent ovarian cancer treated with pegylated liposomal
      doxorubicin (PLD) or topotecan and to compare the CA125 trends between the two
      chemotherapeutics. PATIENTS AND METHODS: Patients with recurrent ovarian cancer,
      all of whom had measurable or evaluable disease, were randomized to receive 50
      mg/m2 PLD every 28 days (n = 239) or 1.5 mg/m2 topotecan for 5 days every 21 days
      (n = 235) as part of a previously reported multicenter study. CA125 measurements
      were obtained prior to therapy and with each cycle of administration. Assessable
      patients underwent radiographic evaluation for response after two cycles of
      therapy. Objective responses were compared to trends in CA125 values at the end
      of cycles 1 and 2. CA125 changes were categorized as baseline (+/-10%), +/- 10%
      25% variance, and > 25% variance. RESULTS: Among patients treated with PLD, 50%
      of complete responders (CR) and 41% of partial responders (PR) had increases in
      CA125 from baseline to cycle 1. Increases in CA125 were also seen in topotecan
      treated patients; however, fewer patients had increases (20% and 8%,
      respectively). Overall, 15% of responding patients (CR + PR) receiving PLD and 6%
      receiving topotecan had elevated CA125 after two cycles of therapy. For those
      patients achieving a partial response, 19% of PLD-treated patients and 8% of
      topotecan-treated patients had CA125 levels above baseline at cycle 2.
      CONCLUSIONS: Considerable intrapatient variation in CA125 values is present among
      responding patients. Early increases in CA125 may not predict ultimate outcome,
      especially in PLD-treated patients.

PMID- 17227903
TI  - Increasing chemotherapy in small-cell lung cancer: from dose intensity and
      density to megadoses.
AB  - The hypothesis that increasing cytotoxic dose intensity will improve cancer cure
      rates is compelling. Although supporting evidence for this hypothesis has accrued
      for several tumor types, including lymphomas, breast cancer, and testicular
      cancers, it remains unproven. Small-cell lung cancer is extremely chemo- and
      radiosensitive, with a response rate of 80% achieved routinely, but few patients
      are cured by chemoradiotherapy. In this setting, increased cytotoxic dose
      intensity might improve cure rates. The finding that response rates in small-cell
      lung cancer correlate with received cytotoxic dose intensity merely confirms that
      "less is worse" and "more is better." Within conventional ranges, dose intensity
      can be increased with the support of hematopoietic growth factors and/or by
      shortening treatments intervals; however, dose intensity could be increased by
      only 20%-30%, and a survival advantage has not been clearly demonstrated. Given
      its high chemosensitivity, small-cell lung cancer was one of the first
      malignancies deemed suitable for increasing dose intensity and even for the use
      of a megadose with the support of autologous bone marrow transplantation. Some
      interest is emerging again due to improvements in supportive care, such as the
      availability of hematopoietic growth factors and peripheral blood progenitor
      cells.

PMID- 17227904
TI  - Final report of toxicity and efficacy of a phase II study of oral
      cyclophosphamide, thalidomide, and prednisone for patients with relapsed or
      refractory multiple myeloma: A Hoosier Oncology Group Trial, HEM01-21.
AB  - Thalidomide has direct antimyeloma and immunomodulatory effects. In addition,
      both thalidomide and metronomic chemotherapy inhibit angiogenesis. The synergy of
      such a combination may decrease toxicity while maintaining efficacy. The Hoosier
      Oncology Group conducted a phase II trial of oral cyclophosphamide (50 mg b.i.d.
      for 21 days), thalidomide (200 mg/day), and prednisone (50 mg q.o.d.) (CTP) per
      28-day course in patients with relapsed multiple myeloma (MM). Of the 37 patients
      enrolled, 16 had prior stem cell transplantation. The median follow-up time was
      25.3 months (95% confidence interval [CI] 23.2-27.7). Of 35 patients treated, 22
      patients (62.9%) responded: 7 (20.0%) complete responses, 2 (5.7%) near-complete
      responses, and 13 (37.1%) partial responses. Eight patients (22.9%) had stable
      disease, and three (8.6%) had disease progression. Two patients withdrew from the
      study early due to reasons unrelated to progression or toxicity and were treated
      as nonresponders. The median time to best response and time to progression were
      3.6 months (95% CI 2.8-10.9) and 13.2 months (95% CI 9.4-21.0), respectively. The
      median number of treatment cycles was seven (range 1-12 cycles). Grade III to IV
      toxicities included leukopenia (42.9%; febrile neutropenia, 11.4%), hyperglycemia
      (20%), sensory neuropathy (11.4%), thromboses (8%), and motor neuropathy (5.7%).
      No patient withdrew from the study due to toxicity. The efficacy and low toxicity
      of the CTP regimen support the future development of such an approach in MM.

PMID- 17227905
TI  - Food and Drug Administration drug approval summary: Sunitinib malate for the
      treatment of gastrointestinal stromal tumor and advanced renal cell carcinoma.
AB  - On January 26, 2006, sunitinib (Sutent) received regular approval as monotherapy
      for the treatment of patients with gastrointestinal stromal tumor after disease
      progression on or intolerance to imatinib mesylate (Gleevec). Time-to-tumor
      progression (TTP) of sunitinib-treated patients was superior to that of placebo
      treated patients. Median TTP of sunitinib-treated patients was 27.3 weeks,
      compared with 6.4 weeks for placebo-treated patients (p < .0001). Partial
      responses were observed in 6.8% of sunitinib-treated patients and no placebo
      treated patients. Sunitinib also received accelerated approval on January 26,
      2006, as monotherapy for treatment of advanced renal cell carcinoma (RCC). In two
      single-arm trials of sunitinib in patients with metastatic RCC, partial responses
      were observed in 25.5% (95% confidence interval [CI], 17.5, 34.9) and 36.5% (95%
      CI, 24.7, 49.6) of patients. Median response durations in the two trials were
      27.1 weeks (95% CI, 24.4, incalculable) and 54 weeks (95% CI, 34.3, 70.1).
      Treatment-emergent adverse events in sunitinib-treated patients included
      diarrhea, mucositis, skin abnormalities, altered taste, electrolyte
      abnormalities, hypertension, and diminution in left ventricular ejection
      fraction. Cardiac safety of sunitinib in patients with preexisting cardiac
      abnormalities remains unknown. Based on nonclinical findings, physicians
      prescribing sunitinib should monitor for adrenal insufficiency in patients who
      undergo stressors such as surgery, trauma, or severe infection. Caution should be
      exercised when administering sunitinib in combination with known CYP3A4 inducers
      or inhibitors.

PMID- 17227906
TI  - A randomized, double-blind study of pegylated liposomal doxorubicin for the
      treatment of AIDS-related Kaposi's sarcoma.
AB  - BACKGROUND: Despite a decreased incidence of AIDS-related Kaposi's sarcoma (KS)
      due to the advent of highly active antiretroviral therapy, approximately 15% of
      AIDS patients still develop AIDS-related KS. This study evaluated the clinical
      benefit, tumor response, and safety of pegylated liposomal doxorubicin for the
      treatment of AIDS-related KS. METHODS: This was a double-blind, multicenter study
      that randomized patients with AIDS-related KS to six cycles of pegylated
      liposomal doxorubicin (20 mg/m2; n = 60) or liposomal daunorubicin (40 mg/m2; n =
      19) every 2 weeks. Clinical benefit was assessed using patient questionnaires and
      monitoring of KS-associated symptoms. Tumor responses were assessed using imaging
      techniques, direct measurement of skin lesions, and photographs, when possible.
      RESULTS: Clinical benefit was observed in 48/60 patients (80%) receiving
      pegylated liposomal doxorubicin and was maintained for a median of 62 days
      (range, 28-107 days). Clinical benefit was achieved by 12/19 patients (63.2%)
      receiving liposomal daunorubicin and was maintained for a median of 55 days
      (range, 28-84 +days). Clinical benefit correlated with tumor response. Tumor
      responses were achieved by 55.0% of patients receiving pegylated liposomal
      doxorubicin and 31.6% of patients receiving liposomal daunorubicin. Response
      rates were similar within each treatment group when only those patients without
      changes in antiretroviral therapy during treatment were considered. Adverse
      events associated with pegylated liposomal doxorubicin were neutropenia (30%),
      nausea (28.3%), and asthenia (16.7%). CONCLUSIONS: Pegylated liposomal
      doxorubicin is safe and effective for the treatment of AIDS-related KS, with most
      patients experiencing clinical benefit, tumor response, or both.

PMID- 17227907
TI  - Randomized, double-blind, placebo-controlled crossover trials of venlafaxine for
      hot flashes after breast cancer.
AB  - BACKGROUND: Although venlafaxine reduces self-reported hot flashes, no data have
      established the drug's impact on physiologically documented hot flashes. Two
      randomized, double-blind, placebo-controlled crossover trials examined the
      efficacy of two doses of venlafaxine in relation to physiological and self
      reported hot flashes and other outcomes, including negative affect, fatigue,
      sleep, and quality of life. METHODS:  SAMPLE: 57 breast cancer survivors in the
      low-dose study; 20 in the high-dose study. SETTING: university cancer clinics in
      the Southeast and Midwest. INTERVENTION: 37.5 mg of venlafaxine (low-dose study)
      or 75 mg of venlafaxine (high-dose study). MEASURES: hot flash frequency
      (physiological monitor, diary, and event marker), hot flash severity (diary), hot
      flash bother (diary), and questionnaires for hot flash impact on daily life,
      negative affect, fatigue, sleep, and quality of life. RESULTS: Subjective but not
      physiological hot flash measures showed placebo effects. Venlafaxine resulted in
      modest decreases in hot flashes, but only hot flash interference improved
      differentially at the higher dose. The timing of venlafaxine's effects on hot
      flashes varied by dose. Only women with a > or =50% decrease in physiological hot
      flashes experienced significant improvement in fatigue, sleep quality, and
      quality of life. Although side effects were mild, most patients discontinued
      venlafaxine long-term. CONCLUSIONS: Although venlafaxine resulted in modest and
      acute reductions in hot flashes with few side effects, it may not be tolerable to
      some patients long-term. At least 50% relief in physiological hot flashes may be
      needed for patients to demonstrate improvement in other outcomes, including
      decreased fatigue, improved sleep, and improved quality of life.

PMID- 17227908
TI  - Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to
      long-term hematopoietic stem cells.
AB  - For decades, in vitro expansion of transplantable hematopoietic stem cells (HSCs)
      has been an elusive goal. Here, we demonstrate that multipotent adult progenitor
      cells (MAPCs), isolated from green fluorescent protein (GFP)-transgenic mice and
      expanded in vitro for >40-80 population doublings, are capable of multilineage
      hematopoietic engraftment of immunodeficient mice. Among MAPC-derived GFP+CD45.2+
      cells in the bone marrow of engrafted mice, HSCs were present that could
      radioprotect and reconstitute multilineage hematopoiesis in secondary and
      tertiary recipients, as well as myeloid and lymphoid hematopoietic progenitor
      subsets and functional GFP+ MAPC-derived lymphocytes that were functional.
      Although hematopoietic contribution by MAPCs was comparable to control KTLS HSCs,
      approximately 10(3)-fold more MAPCs were required for efficient engraftment.
      Because GFP+ host-derived CD45.1+ cells were not observed, fusion is not likely
      to account for the generation of HSCs by MAPCs.

PMID- 17227909
TI  - Helper T cell IL-2 production is limited by negative feedback and STAT-dependent
      cytokine signals.
AB  - Although required for many fundamental immune processes, ranging from self
      tolerance to pathogen immunity, interleukin (IL)-2 production is transient, and
      the mechanisms underlying this brevity remain unclear. These studies reveal that
      helper T cell IL-2 production is limited by a classic negative feedback loop that
      functions autonomously or in collaboration with other common gamma chain (IL-4
      and IL-7) and IL-6/IL-12 family cytokines (IL-12 and IL-27). Consistent with this
      model for cytokine-dependent regulation, they also demonstrate that the
      inhibitory effect can be mediated by several signal transducer and activator of
      transcription (STAT) family transcription factors, namely STAT5, STAT4, and
      STAT6. Collectively, these findings establish that IL-2 production is limited by
      a network of autocrine and paracrine signals that are readily available during
      acute inflammatory responses and, thus, provide a cellular and molecular basis
      for its transient pattern of expression.

PMID- 17227910
TI  - Regulation of IL-27 p28 gene expression in macrophages through MyD88- and
      interferon-gamma-mediated pathways.
AB  - Interleukin (IL)-27 is the newest member of the IL-12 family of heterodimeric
      cytokines composed of the Epstein-Barr virus-induced gene 3 and p28 chains. IL-27
      not only plays an important role in the regulation of differentiation of naive T
      helper cells but also possesses antiinflammatory properties. IL-27 is an early
      product of activated monocytes/macrophages and dendritic cells. However, the
      mechanisms whereby inflammatory signals stimulate IL-27 production have not been
      explored. In this study, we investigated the transcriptional regulation of the
      mouse IL-27 p28 gene in macrophages in response to lipopolysaccharide (LPS) and
      interferon (IFN)-gamma. We found that LPS-stimulated p28 production was
      completely dependent on the Toll-like receptor 4/myeloid differentiation factor
      88 (MyD88)-mediated pathway but only partially dependent on nuclear factor kappaB
      c-Rel. IFN-gamma-induced p28 production/secretion was also partially dependent on
      MyD88 but independent of c-Rel. We then cloned the mouse p28 gene promoter and
      mapped its multiple transcription initiation sites. Furthermore, we identified
      critical promoter elements that mediate the inductive effects of LPS and IFN
      gamma, separately and synergistically, on p28 gene transcription in a c-Rel- and
      interferon regulatory factor 1-dependent manner, respectively.

PMID- 17227911
TI  - The antiinflammatory activity of IgG: the intravenous IgG paradox.
AB  - How high doses of intravenous IgG (IVIG) suppress autoimmune diseases remains
      unresolved. We have recently shown that the antiinflammatory activity of IVIG can
      be attributed to a minor species of IgGs that is modified with terminal sialic
      acids on their Fc-linked glycans. Here we propose that these Fc-sialylated IgGs
      engage a unique receptor on macrophages that, in turn, leads to the upregulation
      of an inhibitory Fcgamma receptor (FcgammaR), thereby protecting against
      autoantibody-mediated pathology.

PMID- 17227912
TI  - Detection of chromatin-associated single-stranded DNA in regions targeted for
      somatic hypermutation.
AB  - After encounter with antigen, the antibody repertoire is shaped by somatic
      hypermutation (SHM), which leads to an increase in the affinity of antibodies for
      the antigen, and class-switch recombination (CSR), which results in a change in
      the effector function of antibodies. Both SHM and CSR are initiated by activation
      induced cytidine deaminase (AID), which deaminates deoxycytidine to deoxyuridine
      in single-stranded DNA (ssDNA). The precise mechanism responsible for the
      formation of ssDNA in V regions undergoing SHM has yet to be experimentally
      established. In this study, we searched for ssDNA in mutating V regions in which
      DNA-protein complexes were preserved in the context of chromatin in human B cell
      lines and in primary mouse B cells. We found that V regions that undergo SHM were
      enriched in short patches of ssDNA, rather than R loops, on both the coding and
      noncoding strands. Detection of these patches depended on the presence of DNA
      associated proteins and required active transcription. Consistent with this, we
      found that both DNA strands in the V region were transcribed. We conclude that
      regions of DNA that are targets of SHM assemble protein-DNA complexes in which
      ssDNA is exposed, making it accessible to AID.

PMID- 17227915
TI  - IFNgamma: issuing macrophages a license to kill.
AB  - T cells tell macrophages when to start making the toxic soup of lysosomal
      enzymes, reactive oxygen species, and nitric oxide that destroys intracellular
      pathogens. In 1983, Carl Nathan proved that this start signal comes in the form
      of the secreted cytokine IFNgamma.

PMID- 17227914
TI  - T cell self-reactivity forms a cytokine milieu for spontaneous development of IL
      17+ Th cells that cause autoimmune arthritis.
AB  - This report shows that highly self-reactive T cells produced in mice as a result
      of genetically altered thymic T cell selection spontaneously differentiate into
      interleukin (IL)-17-secreting CD4+ helper T (Th) cells (Th17 cells), which
      mediate an autoimmune arthritis that clinically and immunologically resembles
      rheumatoid arthritis (RA). The thymus-produced self-reactive T cells, which
      become activated in the periphery via recognition of major histocompatibility
      complex/self-peptide complexes, stimulate antigen-presenting cells (APCs) to
      secrete IL-6. APC-derived IL-6, together with T cell-derived IL-6, drives naive
      self-reactive T cells to differentiate into arthritogenic Th17 cells. Deficiency
      of either IL-17 or IL-6 completely inhibits arthritis development, whereas
      interferon (IFN)-gamma deficiency exacerbates it. The generation,
      differentiation, and persistence of arthritogenic Th17 cells per se are, however,
      insufficient for producing overt autoimmune arthritis. Yet overt disease is
      precipitated by further expansion and activation of autoimmune Th17 cells, for
      example, via IFN-gamma deficiency, homeostatic proliferation, or stimulation of
      innate immunity by microbial products. Thus, a genetically determined T cell self
      reactivity forms a cytokine milieu that facilitates preferential differentiation
      of self-reactive T cells into Th17 cells. Extrinsic or intrinsic stimuli further
      expand these cells, thereby triggering autoimmune disease. Intervention in these
      events at cellular and molecular levels is useful to treat and prevent autoimmune
      disease, in particular RA.

PMID- 17227913
TI  - Mechanism of thioamide drug action against tuberculosis and leprosy.
AB  - Thioamide drugs, ethionamide (ETH) and prothionamide (PTH), are clinically
      effective in the treatment of Mycobacterium tuberculosis, M. leprae, and M. avium
      complex infections. Although generally considered second-line drugs for
      tuberculosis, their use has increased considerably as the number of multidrug
      resistant and extensively drug resistant tuberculosis cases continues to rise.
      Despite the widespread use of thioamide drugs to treat tuberculosis and leprosy,
      their precise mechanisms of action remain unknown. Using a cell-based activation
      method, we now have definitive evidence that both thioamides form covalent
      adducts with nicotinamide adenine dinucleotide (NAD) and that these adducts are
      tight-binding inhibitors of M. tuberculosis and M. leprae InhA. The crystal
      structures of the inhibited M. leprae and M. tuberculosis InhA complexes provide
      the molecular details of target-drug interactions. The purified ETH-NAD and PTH
      NAD adducts both showed nanomolar Kis against M. tuberculosis and M. leprae InhA.
      Knowledge of the precise structures and mechanisms of action of these drugs
      provides insights into designing new drugs that can overcome drug resistance.

PMID- 17227916
TI  - The role of S4 charges in voltage-dependent and voltage-independent KCNQ1
      potassium channel complexes.
AB  - Voltage-gated potassium (Kv) channels extend their functional repertoire by
      coassembling with MinK-related peptides (MiRPs). MinK slows the activation of
      channels formed with KCNQ1 alpha subunits to generate the voltage-dependent I(Ks)
      channel in human heart; MiRP1 and MiRP2 remove the voltage dependence of KCNQ1 to
      generate potassium "leak" currents in gastrointestinal epithelia. Other Kv alpha
      subunits interact with MiRP1 and MiRP2 but without loss of voltage dependence;
      the mechanism for this disparity is unknown. Here, sequence alignments revealed
      that the voltage-sensing S4 domain of KCNQ1 bears lower net charge (+3) than that
      of any other eukaryotic voltage-gated ion channel. We therefore examined the role
      of KCNQ1 S4 charges in channel activation using alanine-scanning mutagenesis and
      two-electrode voltage clamp. Alanine replacement of R231, at the N-terminal side
      of S4, produced constitutive activation in homomeric KCNQ1 channels, a phenomenon
      not observed with previous single amino acid substitutions in S4 of other
      channels. Homomeric KCNQ4 channels were also made constitutively active by
      mutagenesis to mimic the S4 charge balance of R231A-KCNQ1. Loss of single S4
      charges at positions R231 or R237 produced constitutively active MinK-KCNQ1
      channels and increased the constitutively active component of MiRP2-KCNQ1
      currents. Charge addition to the CO2H-terminal half of S4 eliminated constitutive
      activation in MiRP2-KCNQ1 channels, whereas removal of homologous charges from
      KCNQ4 S4 produced constitutively active MiRP2-KCNQ4 channels. The results
      demonstrate that the unique S4 charge paucity of KCNQ1 facilitates its unique
      conversion to a leak channel by ancillary subunits such as MiRP2.

PMID- 17227917
TI  - Importance of hydration and dynamics on the selectivity of the KcsA and NaK
      channels.
AB  - Fundamental concepts governing ion selectivity in narrow pores are reviewed and
      the microscopic factors responsible for the lack of selectivity of the NaK
      channel, which is structurally similar to the K+-selective KcsA channel, are
      elucidated on the basis of all-atom molecular dynamics free energy simulations.
      The results on NaK are contrasted and compared with previous studies of the KcsA
      channel. Analysis indicates that differences in hydration of the cation in the
      pore of NaK is at the origin of the lack of selectivity of NaK.

PMID- 17227920
TI  - Abdominal wall reconstruction after temporary abdominal closure: A ten-year
      review.
AB  - Abdominal wall reconstruction (AWR) is often required for hernias created after
      temporary abdominal closure (TAC). Demographic and clinical data from patients
      undergoing TAC and AWR between January 1, 1992, and December 31, 2002, were
      collected and univariate analysis performed. Temporary abdominal closure and AWR
      were performed in 21 patients. Complications developed in 12 patients (57.1%)
      after TAC; associated risk factors were mesh placement (P = .04) and skin
      grafting (P = .04). Successful AWR included mesh (n = 6), component separation (n
      = 6), primary repair (n = 4), and 3 combination techniques. Six patients (28.6%)
      developed intraoperative complications, and 14 (66.7%) developed postoperative
      complications. Intraoperative complications were increased in patients with
      tissue expanders (P = .01). Postoperative complications (P = .04) were less
      likely with component separation. The complication rate with TAC and AWR is high.
      Tissue expanders are associated with an increased risk of intraoperative
      complications with AWR, whereas component separation is associated with a
      reduction in postoperative complications.

PMID- 17227921
TI  - Laparoscopic resection of clinically suspected gastric stromal tumors.
AB  - Gastrointestinal stromal tumors (GISTs) account for 5% of all gastric tumors.
      Preoperative diagnosis is relatively difficult because biopsy samples are rarely
      obtained during fibergastroscopy. Surgical radical resection is the gold standard
      treatment, allowing pathologic study for both diagnosis and prognosis.
      Laparoscopic resection has become an alternative to the open approach, but long
      term results are not well known. The aim of this study is to report experience
      with laparoscopic resection, placing special emphasis on preoperative diagnosis
      and describing long-term results. A retrospective analysis was made of all
      patients undergoing a laparoscopic resection for clinically suspected
      gastrointestinal stromal tumors between November 1998 and August 2006 at 2
      tertiary hospitals. The medical records of all participants were reviewed
      regarding surgical technique, clinicopathologic features, and postoperative long
      term outcome. Laparoscopic gastric resection was attempted in 22 patients (13
      women and 9 men) with a mean age of 66.7 years (range, 29-84 years). One patient
      had 2 gastric tumors. Tumor localization was upper gastric third in 6 patients,
      mid-gastric third in 7, and distal third in 10. Surgical techniques were
      transgastric submucosal excision (n = 1), wedge resection (n = 13), partial
      gastrectomy with Y-en-Roux reconstruction (n = 6), and total gastrectomy with Y
      en-Roux reconstruction (n = 2). Two patients (9.1%) required conversion to the
      open procedure because of tumor size. Postoperative morbidity was delayed gastric
      emptying in 3 patients. Median postoperative stay was 6 days (range, 4-32 days).
      Pathologic and immunohistochemical study confirmed gastrointestinal stromal
      tumors in 18 cases. The other 4 cases were adenomyoma, hamartoma, plasmocytoma,
      and parasitic tumor (anisakis). Median tumor size was 5.6 cm (range, 2.5-12.5 cm)
      in cases of gastrointestinal stromal tumors. Malignant risk of gastrointestinal
      stromal tumors assessed according to mitotic index and size was low (n = 8),
      intermediate (n = 6), or high (n = 4). After a median follow-up of 32 months
      (range, 1-72 months), there was 1 case of recurrence of GIST. Definitive
      preoperative diagnosis of gastric submucosal tumors is frequently difficult. The
      laparoscopic approach to surgical treatment of these tumors seems safe and is
      associated with acceptable intermediate-term results, especially in cases of
      gastrointestinal stromal tumors.

PMID- 17227918
TI  - The location of a closed channel gate in the GABAA receptor channel.
AB  - Considerable controversy surrounds the location of the closed channel gate in
      members of the Cys-loop receptor family of neurotransmitter-gated ion channels
      that includes the GABAA, glycine, acetylcholine, and 5-HT3 receptors. Cysteine
      accessibility studies concluded that the gate is near the cytoplasmic end of the
      channel in acetylcholine and GABAA receptors but in the middle of the 5-HT3A
      receptor channel. Zn2+ accessibility studies in a chimeric 5-HT3-ACh receptor
      suggested the gate is near the channel's cytoplasmic end. In the 4-A resolution
      structure of the acetylcholine receptor closed state determined by cryoelectron
      microscopy, the narrowest region, inferred to be the gate, is in the channel's
      midsection from 9' to 14' but the M1-M2 loop residues at the channel's
      cytoplasmic end were not resolved in that structure. We used blocker trapping
      experiments with picrotoxin, a GABAA receptor open channel blocker, to determine
      whether a gate exists at a position more extracellular than the picrotoxin
      binding site, which is in the vicinity of alpha1Val257 (2') near the channel's
      cytoplasmic end. We show that picrotoxin can be trapped in the channel after
      removal of GABA. By using the state-dependent accessibility of engineered
      cysteines as reporters for the channel's structural state we infer that after
      GABA washout, with picrotoxin trapped in the channel, the channel appears to be
      in the closed state. We infer that a gate exists between the picrotoxin binding
      site and the channel's extracellular end, consistent with a closed channel gate
      in the middle of the channel. Given the homology with acetylcholine and 5-HT3
      receptors there is probably a similar gate in those channels as well. This does
      not preclude the existence of an additional gate at a more cytoplasmic location.

PMID- 17227922
TI  - A randomized controlled trial of laparoscopic nissen fundoplication versus proton
      pump inhibitors for treatment of patients with chronic gastroesophageal reflux
      disease: One-year follow-up.
AB  - A randomized controlled trial conducted in patients with gastroesophageal reflux
      disease compared optimized medical therapy using proton pump inhibitor (n = 52)
      with laparoscopic Nissen fundoplication (n = 52). Patients were monitored for 1
      year. The primary end point was frequency of gastroesophageal reflux dis-ease
      symptoms. Surgical patients had improved symptoms, pH control, and overall
      quality of life health index after surgery at 1 year compared with the medical
      group. The overall gastroesophageal reflux disease symptom score at 1 year was
      unchanged in the medical patients, but improved in the surgical patients.
      Fourteen patients in the medical arm experienced symptom relapse requiring
      titration of the proton pump inhibitor dose, but 6 had satisfactory symptom
      remission. No surgical patients required additional treatment for symptom
      control. Patients controlled on long-term proton pump inhibitor therapy for
      chronic gastroesophageal reflux disease are excellent surgical candidates and
      should experience improved symptom control after surgery at 1 year.

PMID- 17227923
TI  - How are decisions to introduce new surgical technologies made? Advanced
      laparoscopic surgery at a Canadian community hospital: A qualitative case study
      and evaluation.
AB  - The introduction of many new surgical technologies is associated with increased
      costs and uncertainty regarding risks and benefits. Currently, little is known
      about how decisions are made regarding the adoption of surgical innovations. To
      study the decision-making process for adoption of advanced laparoscopic surgical
      procedures at a community hospital in Toronto, Canada, we used qualitative case
      study methods. Data were collected using semi-structured interviews with key
      informants. We performed a modified thematic analysis of the data, using the
      conceptual framework for priority setting known as accountability for
      reasonableness, which consists of 4 conditions: relevance, publicity, appeals,
      and enforcement. Several advanced laparoscopic surgical procedures were
      introduced at the hospital between 2000 and 2005. During that time, there was no
      structured, explicit process for making decisions about introducing new surgical
      technologies. Use of the new surgical technologies was relevant, as measured by
      the perception of patient benefit and alignment with the hospital's strategic
      priorities. There was no systematic structure in place to oversee publicity,
      appeals, or enforcement. The decision to adopt advanced laparoscopic surgery at a
      community hospital in Toronto, Canada, was made primarily on the basis of its
      relevance to patient care. The process for making decisions about the adoption of
      new surgical technologies can be improved.

PMID- 17227924
TI  - The effect of direct-from-recovery room discharge of laparoscopic cholecystectomy
      patients on recovery room workload.
AB  - Ambulatory laparoscopic cholecystectomy pathways move patients through the
      hospital without encountering delays caused by congested inpatient bed units.
      However, redirecting patients to a direct discharge pathway might not be
      beneficial if recovery capacity is further taxed by additional workload. In this
      study, we attempt to assess the operational impact on recovery room workload of
      directly discharging laparoscopic cholecystectomy patients to home. We conducted
      a retrospective case-control review of recovery room flow sheets to determine
      recovery room time and effort required for laparoscopic cholecystectomy patients.
      The study was restricted to patients of a single surgeon to minimize confounds
      from surgical technique. Fifty-seven case patients (May 1, 2004, through November
      30, 2004), all managed with intent to directly discharge from the recovery room,
      were compared with control patients (n = 81) from the corresponding 6 months in
      the year before the direct-discharge plan. The times (mean; 95% confidence
      interval) to meet objective criteria for adequate pain control (3.5 minutes [2.1
      to 5.9] versus 4.0 minutes [2.6 to 6.1]) and readiness for discharge from phase 1
      recovery (8.1 minutes [4.8 to 13.6] versus 6.1 minutes [4.0 to 9.5]) were not
      different between the groups. The number and distribution of interventions
      documented in the recovery process were not different between groups, nor was
      there a difference in recovery room length of stay (158 minutes [138 to 182]
      versus 149 minutes [132 to 167]). In our study, recovery room records reveal
      little if any increased workload associated with the direct-to-home discharge of
      laparoscopic cholecystectomy patients.

PMID- 17227925
TI  - Life expectancy benefits of gastric bypass surgery.
AB  - Bariatric surgery is the most effective treatment for achieving sustained weight
      loss in morbidly obese patients. Although the use of gastric bypass is growing
      rapidly, the potential life expectancy benefits of the procedure are unknown. We
      created a Markov decision analysis model to examine the effect of gastric bypass
      surgery on life expectancy in morbidly obese patients (body mass index [BMI] = 40
      kg/m2). Input assumptions for the model were obtained from published life tables
      (baseline mortality risks), epidemiologic studies (obesity-related excess
      mortality), and large case series (surgical outcomes). In our baseline analysis,
      a 40-year-old woman (BMI = 40 kg/m2) would gain 2.6 years of life expectancy by
      undergoing gastric bypass (38.7 years versus 36.2 years without surgery). In
      sensitivity analysis, life-years gained with surgery remained substantial when
      assumptions were varied across reasonable ranges for surgical mortality risk (1.0
      3.0 years) and effectiveness (0.9-4.4 years). Life-years gained with gastric
      bypass surgery did not vary considerably by age and sex subgroups. Relative to
      other major surgical procedures, gastric bypass for morbid obesity is associated
      with substantial gains in life expectancy. Long- term data from prospective
      studies are needed to confirm this finding.

PMID- 17227926
TI  - Classifying cause of death after cancer surgery.
AB  - A retrospective, single-center study was conducted to understand variation in
      mortality after elective cancer surgery. Fifty-two patients who died
      perioperatively after elective cancer resections (colon, esophageal, pancreatic,
      lung, gastric and liver) were identified. A methodology was developed and used
      during medical record review to capture the occurrence and chronology of 21
      postoperative complications. Data were reviewed by 3 attending surgeons who
      assigned cause of death based on information from the entire clinical record.
      This methodology demonstrated good construct validity, with 81% agreement between
      cause of death assigned by expert review of data from the instrument and that
      assigned by expert review of the clinical records (kappa = 0.75, P < .005). Cause
      specific mortality can be reliably and systematically measured after cancer
      surgery. Understanding variation in cause-specific mortality can inform future
      quality improvement efforts.

PMID- 17227927
TI  - The future of teaching surgical endoscopy.
AB  - Gastrointestinal surgery, with its emphasis on endoscopy, has renewed interest in
      teaching surgical endoscopy. The field is rapidly evolving, with innovative
      techniques emanating from the laboratory to the operating room and endoscopy
      suite. To ensure that surgeons spearhead the field of endoscopic surgery, a new
      strategy for teaching surgical endoscopy to residents and practicing surgeons
      must be developed.

PMID- 17227929
TI  - Innovation and the surgical trainee.

PMID- 17227928
TI  - Simulation for training with the Autosuture Endo Stitch device.
AB  - The rapid development and deployment of novel laparoscopic instruments present
      the surgical educator and trainee with a significant challenge. Several useful
      instruments have been particularly difficult to teach the novice. We have
      developed a platform that allows the combination of the actual instrument handle
      with a virtual re-creation of the instrument tip. We chose the Autosuture Endo
      Stitch device as the prototypical instrument because it satisfies our subjective
      experience of "useful, but hard to teach." A software package was developed to
      support the re-creation of the needle and suture that accompany the device. The
      apparatus has haptic capabilities and collision detection so that the needle
      driver is "aware" of suture and instrument contact. The developed virtual
      environment allows re-creation of the necessary motion to simulate the
      instrument, the trainee can use the actual instrument handle, and the system can
      be altered to accommodate other instruments.

PMID- 17227930
TI  - "Splenectomy: From bucket to bag".

PMID- 17227931
TI  - Summaries for patients. Comparison of survival among HIV-infected and noninfected
      people in Denmark, 1995-2005.

PMID- 17227932
TI  - Survival of persons with and without HIV infection in Denmark, 1995-2005.
AB  - BACKGROUND: The expected survival of HIV-infected patients is of major public
      health interest. OBJECTIVE: To estimate survival time and age-specific mortality
      rates of an HIV-infected population compared with that of the general population.
      DESIGN: Population-based cohort study. SETTING: All HIV-infected persons
      receiving care in Denmark from 1995 to 2005. PATIENTS: Each member of the
      nationwide Danish HIV Cohort Study was matched with as many as 99 persons from
      the general population according to sex, date of birth, and municipality of
      residence. MEASUREMENTS: The authors computed Kaplan-Meier life tables with age
      as the time scale to estimate survival from age 25 years. Patients with HIV
      infection and corresponding persons from the general population were observed
      from the date of the patient's HIV diagnosis until death, emigration, or 1 May
      2005. RESULTS: 3990 HIV-infected patients and 379,872 persons from the general
      population were included in the study, yielding 22,744 (median, 5.8 y/person) and
      2,689,287 (median, 8.4 years/person) person-years of observation. Three percent
      of participants were lost to follow-up. From age 25 years, the median survival
      was 19.9 years (95% CI, 18.5 to 21.3) among patients with HIV infection and 51.1
      years (CI, 50.9 to 51.5) among the general population. For HIV-infected patients,
      survival increased to 32.5 years (CI, 29.4 to 34.7) during the 2000 to 2005
      period. In the subgroup that excluded persons with known hepatitis C coinfection
      (16%), median survival was 38.9 years (CI, 35.4 to 40.1) during this same period.
      The relative mortality rates for patients with HIV infection compared with those
      for the general population decreased with increasing age, whereas the excess
      mortality rate increased with increasing age. LIMITATIONS: The observed mortality
      rates are assumed to apply beyond the current maximum observation time of 10
      years. CONCLUSIONS: The estimated median survival is more than 35 years for a
      young person diagnosed with HIV infection in the late highly active
      antiretroviral therapy era. However, an ongoing effort is still needed to further
      reduce mortality rates for these persons compared with the general population.

PMID- 17227933
TI  - Effect of New York State regulatory action on benzodiazepine prescribing and hip
      fracture rates.
AB  - BACKGROUND: Medicare Part D excludes benzodiazepines from coverage, and numerous
      state government policies limit use of benzodiazepines. No data indicate that
      such policies have decreased the incidence of hip fracture. OBJECTIVE: To assess
      whether a statewide policy that decreased the use of benzodiazepines among
      elderly persons by more than 50% has decreased the incidence of hip fracture.
      DESIGN: A quasi-experiment comparing changes in outcomes before and after a
      policy change in a study U.S. state (New York) and a control state (New Jersey).
      SETTING: Two U.S. state Medicaid programs, 1988-1990. PATIENTS: Medicaid
      enrollees in New York (n = 51 529) and New Jersey (n = 42 029) who received or
      did not receive a benzodiazepine. MEASUREMENTS: Benzodiazepine prescribing and
      hazard ratios for hip fracture, adjusted for age and eligibility category.
      INTERVENTION: A statewide policy, implemented in New York in 1989, that required
      triplicate forms for benzodiazepine prescribing to allow surveillance by health
      authorities. RESULTS: The triplicate prescription policy immediately resulted in
      a 60.3% (95% CI, -66.3% to -54.2%) reduction in benzodiazepine use among women
      and 58.5% (-64.3% to -52.8%) among men. Benzodiazepine use in New Jersey remained
      stable. Hazard ratios for hip fracture that were adjusted for age and eligibility
      category did not change in New York or New Jersey when the periods before and
      after use of the triplicate prescription policy were compared (change from 1.2 to
      1.1 among female benzodiazepine recipients [P = 0.70], 1.3 to 1.1 [P = 0.08]
      among female nonrecipients, 0.8 to 1.1 [P = 0.56] among male recipients, and 1.1
      to 1.3 [P = 0.46] among male nonrecipients). LIMITATIONS: Information was lacking
      on race, benzodiazepine dose, and other potential determinants of continued
      benzodiazepine prescribing. CONCLUSIONS: Policies that lead to substantial
      reductions in the use of benzodiazepines among elderly persons do not necessarily
      lead to decreased incidence of hip fracture. Limitations on coverage of
      benzodiazepines under Medicare Part D may not achieve this widely assumed
      clinical benefit.

PMID- 17227934
TI  - Systematic review: the safety and efficacy of growth hormone in the healthy
      elderly.
AB  - BACKGROUND: Human growth hormone (GH) is widely used as an antiaging therapy,
      although its use for this purpose has not been approved by the U.S. Food and Drug
      Administration and its distribution as an antiaging agent is illegal in the
      United States. PURPOSE: To evaluate the safety and efficacy of GH therapy in the
      healthy elderly. DATA SOURCES: The authors searched MEDLINE and EMBASE databases
      for English-language studies published through 21 November 2005 by using such
      terms as growth hormone and aging. STUDY SELECTION: The authors included
      randomized, controlled trials that compared GH therapy with no GH therapy or GH
      and lifestyle interventions (exercise with or without diet) with lifestyle
      interventions alone. Included trials provided GH for 2 weeks or more to community
      dwelling participants with a mean age of 50 years or more and a body mass index
      of 35 kg/m2 or less. The authors excluded studies that evaluated GH as treatment
      for a specific illness. DATA EXTRACTION: Two authors independently reviewed
      articles and abstracted data. DATA SYNTHESIS: 31 articles describing 18 unique
      study populations met the inclusion criteria. A total of 220 participants who
      received GH (107 person-years) completed their respective studies. Study
      participants were elderly (mean age, 69 years [SD, 6]) and overweight (mean body
      mass index, 28 kg/m2 [SD, 2]). Initial daily GH dose (mean, 14 microg per kg of
      body weight [SD, 7]) and treatment duration (mean, 27 weeks [SD, 16]) varied. In
      participants treated with GH compared with those not treated with GH, overall fat
      mass decreased (change in fat mass, -2.1 kg [95% CI, -2.8 to -1.35] and overall
      lean body mass increased (change in lean body mass, 2.1 kg [CI, 1.3 to 2.9]) (P <
      0.001), and their weight did not change significantly (change in weight, 0.1 kg
      [CI, -0.7 to 0.8]; P = 0.87). Total cholesterol levels decreased (change in
      cholesterol, -0.29 mmol/L [-11.21 mg/dL]; P = 0.006), although not significantly
      after adjustment for body composition changes. Other outcomes, including bone
      density and other serum lipid levels, did not change. Persons treated with GH
      were significantly more likely to experience soft tissue edema, arthralgias,
      carpal tunnel syndrome, and gynecomastia and were somewhat more likely to
      experience the onset of diabetes mellitus and impaired fasting glucose.
      LIMITATIONS: Some important outcomes were infrequently or heterogeneously
      measured and could not be synthesized. Most included studies had small sample
      sizes. CONCLUSIONS: The literature published on randomized, controlled trials
      evaluating GH therapy in the healthy elderly is limited but suggests that it is
      associated with small changes in body composition and increased rates of adverse
      events. On the basis of this evidence, GH cannot be recommended as an antiaging
      therapy.

PMID- 17227935
TI  - Systematic review: opioid treatment for chronic back pain: prevalence, efficacy,
      and association with addiction.
AB  - BACKGROUND: The prevalence, efficacy, and risk for addiction for persons
      receiving opioids for chronic back pain are unclear. PURPOSE: To determine the
      prevalence of opioid treatment, whether opioid medications are effective, and the
      prevalence of substance use disorders among patients receiving opioid medications
      for chronic back pain. DATA SOURCES: English-language studies from MEDLINE (1966
      March 2005), EMBASE (1966-March 2005), Cochrane Central Register of Controlled
      Clinical Trials (to 4th quarter 2004), PsychInfo (1966-March 2005), and retrieved
      references. STUDY SELECTION: Articles that studied an adult, nonobstetric sample;
      used oral, topical, or transdermal opioids; and focused on treatment for chronic
      back pain. DATA EXTRACTION: Two investigators independently extracted data and
      determined study quality. DATA SYNTHESIS: Opioid prescribing varied by treatment
      setting (range, 3% to 66%). Meta-analysis of the 4 studies assessing the efficacy
      of opioids compared with placebo or a nonopioid control did not show reduced pain
      with opioids (g, -0.199 composite standardized mean difference [95% CI, -0.49 to
      0.11]; P = 0.136). Meta-analysis of the 5 studies directly comparing the efficacy
      of different opioids demonstrated a nonsignificant reduction in pain from
      baseline (g, -0.93 composite standardized mean difference [CI, -1.89 to -0.03]; P
      = 0.055). The prevalence of lifetime substance use disorders ranged from 36% to
      56%, and the estimates of the prevalence of current substance use disorders were
      as high as 43%. Aberrant medication-taking behaviors ranged from 5% to 24%.
      LIMITATIONS: Retrieval and publication biases and poor study quality. No trial
      evaluating the efficacy of opioids was longer than 16 weeks. CONCLUSIONS: Opioids
      are commonly prescribed for chronic back pain and may be efficacious for short
      term pain relief. Long-term efficacy (> or =16 weeks) is unclear. Substance use
      disorders are common in patients taking opioids for back pain, and aberrant
      medication-taking behaviors occur in up to 24% of cases.

PMID- 17227936
TI  - Update in neurology.

PMID- 17227938
TI  - Scream.

PMID- 17227937
TI  - Incorporating quality of evidence into decision analytic modeling.
AB  - Our objective was to illustrate the effects of using stricter standards for the
      quality of evidence used in decision analytic modeling. We created a simple 10
      parameter probabilistic Markov model to estimate the cost-effectiveness of
      directly observed therapy (DOT) for individuals with newly diagnosed HIV
      infection. We evaluated quality of evidence on the basis of U.S. Preventive
      Services Task Force methods, which specified 3 separate domains: study design,
      internal validity, and external validity. We varied the evidence criteria for
      each of these domains individually and collectively. We used published research
      as a source of data only if the quality of the research met specified criteria;
      otherwise, we specified the parameter by randomly choosing a number from a range
      within which every number has the same probability of being selected (a uniform
      distribution). When we did not eliminate poor-quality evidence, DOT improved
      health 99% of the time and cost less than 100,000 dollars per additional quality
      adjusted life-year (QALY) 85% of the time. The confidence ellipse was extremely
      narrow, suggesting high precision. When we used the most rigorous standards of
      evidence, we could use fewer than one fifth of the data sources, and DOT improved
      health only 49% of the time and cost less than 100,000 dollars per additional
      QALY only 4% of the time. The confidence ellipse became much larger, showing that
      the results were less precise. We conclude that the results of decision modeling
      may vary dramatically depending on the stringency of the criteria for selecting
      evidence to use in the model.

PMID- 17227939
TI  - Deflection of a diagnosis.

PMID- 17227940
TI  - Acupuncture and knee osteoarthritis.

PMID- 17227941
TI  - Acupuncture and knee osteoarthritis.

PMID- 17227942
TI  - Acupuncture and knee osteoarthritis.

PMID- 17227943
TI  - Redesigning residency education in internal medicine.

PMID- 17227944
TI  - Diastolic blood pressure in coronary artery disease.

PMID- 17227945
TI  - A rare mimic of hereditary hemorrhagic telangiectasia and conjunctivitis.

PMID- 17227946
TI  - Facing an uncertain climate.

PMID- 17227947
TI  - Neuroendocrine self-control: dendritic release of vasopressin.

PMID- 17227948
TI  - Endocannabinoids link rapid, membrane-mediated corticosteroid actions to
      behavior.

PMID- 17227951
TI  - Hiding human thymidine kinase 1 from APC/C-mediated destruction by thymidine
      binding.
AB  - Thymidine kinase 1 (TK1) is a key cytosolic enzyme in the salvage pathway for
      dTTP synthesis. In mitotic exit, human TK1 (hTK1) is degraded via the anaphase
      promoting complex/cyclosome (APC/C)-Cdh1 pathway to limit dTTP production. In
      this study, we show that thymidine binding stabilizes hTK1 during growth arrest.
      By in vitro degradation, ubiquitination, and Cdh1 binding analyses, we provide
      direct evidence that thymidine binding protects wild-type hTK1 protein from APC/C
      Cdh1-mediated destruction. In contrast, mutant-type hTK1 protein defective in
      thymidine binding ability could still be polyubiquitinated by APC/C-Cdh1 in the
      presence of thymidine. These results suggest that the status of thymidine binding
      to hTK1 protein determines its susceptibility to degradation due to APC/C
      targeting. Our in vivo experimental data also demonstrated that thymidine
      treatment abolished Cdh1/proteasome-responsive suppression of hTK1 expression.
      Moreover, exposure of mitotic-arrested K562 cells to thymidine (100 microM)
      stabilized endogenous TK1, causing nucleotide imbalance in the early G1 phase and
      an increase of S phase accumulation. In conclusion, thymidine is not only a
      substrate of TK1 but also acts as its expression regulator by modulating its
      proteolytic control during mitotic exit, conferring a feed-forward regulation of
      dTTP formation.

PMID- 17227950
TI  - Enhanced CXCL1 production and angiogenesis in adenosine-mediated lung disease.
AB  - Angiogenesis is a feature of chronic lung diseases such as asthma and pulmonary
      fibrosis; however, the pathways controlling pathological angiogenesis during lung
      disease are not completely understood. Adenosine is a signaling molecule that has
      been implicated in the exacerbation of chronic lung disease and in the regulation
      of angiogenesis; however, the relationship between these factors has not been
      investigated. The current study utilized adenosine deaminase (ADA)-deficient mice
      to determine whether chronic elevations in adenosine in vivo result in pulmonary
      angiogenesis. Results demonstrate substantial angiogenesis in the tracheas of ADA
      deficient mice in association with adenosine elevations. ADA replacement enzyme
      therapy resulted in a lowering of adenosine levels and reversal of tracheal
      angiogenesis, indicating that the increases in vessel number are dependent on
      adenosine elevations. Levels of the angiogenic chemokine CXCL1 (mouse functional
      homologue of human IL-8) were found to be elevated in an adenosine-dependent
      manner in the lungs of ADA-deficient mice. Neutralization of CXCL1 and its
      receptor, CXCR2, resulted in the inhibition of angiogenic activity, which
      suggests that CXCL1 signaling through the CXCR2 receptor mediated the observed
      increases in angiogenesis. Our findings suggest that adenosine plays an important
      role, via CXCL1, in the induction of pulmonary angiogenesis.

PMID- 17227953
TI  - Regulation of phagocyte NADPH oxidase activity: identification of two cytochrome
      b558 activation states.
AB  - Activation of the phagocyte NADPH oxidase (phox) requires the association of
      cytosolic proteins (p67-phox, p47-phox, p40-phox, and Rac1/2) with the membrane
      cytochrome b558, leading to a hemoprotein conformation change. To clarify this
      mechanism, the phagocyte NADPH oxidase complex was isolated through cytochrome
      b558 purification after three chromatographic steps. The purified neutrophil
      complex was constitutively active in the absence of an amphiphile agent with a
      maximum turnover (125 mol O2(-) x s(-1) x mol heme b(-1)), indicating that
      cytochrome b558 has been activated by cytosolic proteins and is in an "open
      conformation," able to transfer a maximum rate of electrons. In contrast, the
      phox complex prepared with B lymphocyte cytosol shows a lower constitutive
      turnover (approximately 50 mol O2(-) x s(-1) x mol heme b(-1)). Analysis of phox
      complex components by Western blot and mass spectrometry showed the presence of
      cytosolic factors (especially p67-phox) and structural proteins (moesin, ezrin).
      To investigate the difference in activity of phox complexes, we evaluated the
      effect of MRP8 and MRP14, specifically expressed in neutrophils, on the activity
      of the B lymphocyte complex. MRPs induce the switch between the partially and the
      fully "open" cytochrome b558 conformation. Moreover, their effect was independent
      of p67-phox. Data point out two potential cytochrome b558 activation states.

PMID- 17227952
TI  - Anti-ulcer treatment during pregnancy induces food allergy in mouse mothers and a
      Th2-bias in their offspring.
AB  - The treatment of dyspeptic disorders with anti-acids leads to an increased risk
      of sensitization against food allergens. As these drugs are taken by 30-50% of
      pregnant women due to reflux and heartburn, we aimed here to investigate the
      impact of maternal therapy with anti-acids on the immune response in the
      offspring in a murine model. Codfish extract as model allergen was fed with or
      without sucralfate, an anti-acid drug, to pregnant BALB/c mice during pregnancy
      and lactation. These mothers developed a codfish-specific allergic response shown
      as high IgG1 and IgE antibody levels and positive skin tests. In the next step we
      analyzed whether this maternal sensitization impacts a subsequent sensitization
      in the offspring. Indeed, in stimulated splenocytes of these offspring we found a
      relative Th2-dominance, because the Th1- and T-regulatory cytokines were
      significantly suppressed. Our data provide evidence that the anti-acid drug
      sucralfate supports sensitization against food in pregnant mice and favors a Th2
      milieu in their offspring. From these results we propose that anti-acid treatment
      during pregnancy could be responsible for the increasing number of sensitizations
      against food allergens in young infants.

PMID- 17227954
TI  - Host-symbiont interactions of the primary endosymbiont of human head and body
      lice.
AB  - The first mycetome was discovered more than 340 yr ago in the human louse.
      Despite the remarkable biology and medical and social importance of human lice,
      its primary endosymbiont has eluded identification and characterization. Here, we
      report the host-symbiont interaction of the mycetomic bacterium of the head louse
      Pediculus humanus capitis and the body louse P. h. humanus. The endosymbiont
      represents a new bacterial lineage in the gamma-Proteobacteria. Its closest
      sequenced relative is Arsenophonus nasoniae, from which it differs by more than
      10%. A. nasoniae is a male-killing endosymbiont of jewel wasps. Using
      microdissection and multiphoton confocal microscopy, we show the remarkable
      interaction of this bacterium with its host. This endosymbiont is unique because
      it occupies sequentially four different mycetomes during the development of its
      host, undergoes three cycles of proliferation, changes in length from 2-4 microm
      to more than 100 microm, and has two extracellular migrations, during one of
      which the endosymbionts have to outrun its host's immune cells. The host and its
      symbiont have evolved one of the most complex interactions: two provisional or
      transitory mycetomes, a main mycetome and a paired filial mycetome. Despite the
      close relatedness of body and head lice, differences are present in the mycetomic
      provisioning and the immunological response.

PMID- 17227955
TI  - Protein kinase C-dependent mitochondrial translocation of proapoptotic protein
      Bax on activation of inducible nitric-oxide synthase in rostral ventrolateral
      medulla mediates cardiovascular depression during experimental endotoxemia.
AB  - Sympathetic premotor neurons for the maintenance of vasomotor tone are located in
      rostral ventrolateral medulla (RVLM). We demonstrated previously that
      overproduction of nitric oxide (NO) by inducible NO synthase (iNOS) in RVLM,
      leading to caspase 3-dependent apoptotic cell death, plays a pivotal role in
      cardiovascular depression during endotoxemia induced by intravenous
      administration of Escherichia coli lipopolysaccharide. The interposing
      intracellular events remain unknown. We evaluated the hypothesis that these
      events encompass protein kinase C (PKC) activation, which triggers activation and
      translocation of Bax that opens mitochondrial permeability transition pore by
      interacting with adenine nucleotide translocase (ANT) or voltage-dependent anion
      protein (VDAC), followed by cytosolic release of cytochrome c. In Sprague-Dawley
      rats, coimmunoprecipitation and Western blot analyses revealed sequential
      manifestations during endotoxemia of membrane-bound translocation of PKC,
      dissociation of cytosolic PKC/Bax complex, mitochondrial translocation of
      activated Bax, augmented Bax/ANT or Bax/VDAC association, elevated cytosolic
      cytochrome c and caspase 3, and DNA fragmentation in ventrolateral medulla.
      Microinjection of iNOS inhibitor into bilateral RVLM significantly retarded PKC
      and Bax activation. The induced association of translocated Bax with ANT or VDAC
      and the triggered mitochondrial apoptotic signaling cascade were blunted by
      blockade in RVLM of PKC, mitochondrial translocation of Bax, Bax channels, ANT,
      or caspase 3, alongside significant amelioration of cardiovascular depression. We
      conclude that formation of mitochondrial Bax/ANT or Bax/VDAC complex that
      initiates caspase 3-dependent apoptosis in the RVLM as a result of PKC-dependent
      mitochondrial translocation of activated Bax activated by iNOS-derived NO plays a
      pivotal role in the manifestation of endotoxin-induced cardiovascular depression.

PMID- 17227956
TI  - EGCG, a green tea polyphenol, improves endothelial function and insulin
      sensitivity, reduces blood pressure, and protects against myocardial I/R injury
      in SHR.
AB  - Epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea, may augment
      metabolic and vascular actions of insulin. Therefore, we investigated effects of
      EGCG treatment to simultaneously improve cardiovascular and metabolic function in
      spontaneously hypertensive rats (SHR; model of metabolic syndrome with
      hypertension, insulin resistance, and overweight). In acute studies, EGCG (1-100
      microM) elicited dose-dependent vasodilation in mesenteric vascular beds (MVB)
      isolated from SHR ex vivo that was inhibitable by N(omega)-nitro-L-arginine
      methyl ester (L-NAME; nitric oxide synthase antagonist) or wortmannin
      [phosphatidylinositol (PI) 3-kinase inhibitor]. In chronic studies, 9-wk-old SHR
      were treated by gavage for 3 wk with EGCG (200 mg.kg(-1).day(-1)), enalapril (30
      mg.kg(-1).day(-1)), or vehicle. A separate group of SHR receiving L-NAME (80 mg/l
      in drinking water) was treated for 3 wk with either EGCG or vehicle. Vasodilator
      actions of insulin were significantly improved in MVB from EGCG- or enalapril
      treated SHR (when compared with vehicle-treated SHR). Both EGCG and enalapril
      therapy significantly lowered systolic blood pressure (SBP) in SHR. EGCG therapy
      of SHR significantly reduced infarct size and improved cardiac function in
      Langendorff-perfused hearts exposed to ischemia-reperfusion (I/R) injury. In SHR
      given L-NAME, beneficial effects of EGCG on SBP and I/R were not observed. Both
      enalapril and EGCG treatment of SHR improved insulin sensitivity and raised
      plasma adiponectin levels. We conclude that acute actions of EGCG to stimulate
      production of nitric oxide from endothelium using PI 3-kinase-dependent pathways
      may explain, in part, beneficial effects of EGCG therapy to simultaneously
      improve metabolic and cardiovascular pathophysiology in SHR. These findings may
      be relevant to understanding potential benefits of green tea consumption in
      patients with the metabolic syndrome.

PMID- 17227957
TI  - Autonomic involvement in the permanent metabolic programming of hyperinsulinemia
      in the high-carbohydrate rat model.
AB  - Exposure to a high-carbohydrate (HC) milk formula during the suckling period
      results in permanent metabolic programming of hyperinsulinemia in HC rats.
      Previous studies have shown that hyperinsulinemia in HC rats involves a
      programmed hyperresponsiveness to glucose. However, the immediate onset and
      persistence of enhanced insulin secretion throughout life suggests a role for
      numerous factors that control insulin secretion. Present in vivo and in vitro
      studies have shown a role for altered autonomic activity, including increased
      parasympathetic and decreased sympathetic activities, in the maintenance of
      hyperinsulinemia in 100-day-old HC rats. HC rats were shown to be more sensitive
      to cholinergic-induced potentiation of glucose-stimulated insulin secretion
      (GSIS) in response to acetylcholine and showed increased sensitivity to blockade
      of cholinergic-induced insulin secretion by the muscarinic-type 3 receptor
      specific antagonist 4-diphenylacetoxy-N-methylpiperidine. In addition, HC rats
      were less sensitive to adrenergic-induced inhibition of insulin secretion by
      oxymetazoline, whereas treatment with yohimbine resulted in increased GSIS.
      Furthermore, HC rats showed greater reductions in plasma insulin levels after
      vagotomy, as well as an attenuation of yohimbine-induced potentiation of GSIS,
      suggesting that yohimbine-mediated changes are mediated by parasympathetic
      activity. Changes in autonomic regulation of GSIS are supported by increased mRNA
      levels of the parasympathetic signaling molecules muscarinic-type 3 receptor,
      phospholipase Cbeta1, and protein kinase C-alpha and decreased levels of
      alpha(2a)-adrenergic receptors in islets from adult HC rats. In conclusion,
      metabolic programming of hyperinsulinemia throughout adulthood of HC rats
      involves changes in autonomic activity in response to the HC dietary intervention
      in the suckling period.

PMID- 17227958
TI  - A1 adenosine receptor partial agonist lowers plasma FFA and improves insulin
      resistance induced by high-fat diet in rodents.
AB  - There is substantial evidence in the literature that elevated plasma free fatty
      acids (FFA) play a role in the pathogenesis of type 2 diabetes. CVT-3619 is a
      selective partial A(1) adenosine receptor agonist that inhibits lipolysis and
      lowers circulating FFA. The present study was undertaken to determine the effect
      of CVT-3619 on insulin resistance induced by high-fat (HF) diet in rodents. HF
      diet feeding to rats for 2 wk caused a significant increase in insulin, FFA, and
      triglyceride (TG) concentrations compared with rats fed chow. CVT-3619 (1 mg/kg)
      caused a time-dependent decrease in fasting insulin, FFA, and TG concentrations.
      Acute administration of CVT-3619 significantly lowered the insulin response,
      whereas glucose response was not different with an oral glucose tolerance test.
      Treatment with CVT-3619 for 2 wk resulted in significant lowering of FFA, TG, and
      insulin concentrations in rats on HF diet. To determine the effect of CVT-3619 on
      insulin sensitivity, hyperinsulinemic euglycemic clamp studies were performed in
      C57BL/J6 mice fed HF diet for 12 wk. Glucose infusion rate was decreased
      significantly in HF mice compared with chow-fed mice. CVT-3619 treatment 15 min
      prior to the clamp study significantly (P < 0.01) increased glucose infusion rate
      to values similar to that for chow-fed mice. In conclusion, CVT-3619 treatment
      lowers FFA and TG concentrations and improves insulin sensitivity in rodent
      models of insulin resistance.

PMID- 17227959
TI  - Long-term estrogen deficiency lowers regional blood flow, resting systolic blood
      pressure, and heart rate in exercising premenopausal women.
AB  - The cardiovascular consequences of hypoestrogenism in premenopausal women are
      unclear. Accordingly, the influence of menstrual status and endogenous estrogen
      (E(2)) exposure on blood pressure (BP), heart rate (HR), and calf blood flow in
      young (18-35 yr) regularly exercising premenopausal women with exercise
      associated menstrual aberrations was investigated. Across consecutive menstrual
      cycles, daily urinary ovarian steroid levels were analyzed, and the area under
      the curve was calculated to determine menstrual status and E(2) exposure. BP, HR,
      blood flow, vascular conductance, and resistance were measured at baseline and
      following ischemic calf exercise. Exercising subjects consisted of 14 ovulatory
      (ExOv), 10 short-term (anovulatory and <or=100 days amenorrhea; ST-E(2) Def), and
      8 long-term (>100 days amenorrhea; LT-E(2) Def) E(2)-deficient women. Nine
      sedentary ovulatory subjects (SedOv) were also studied. All groups were similar
      in age (24.8 +/- 0.7 yr), height (164.8 +/- 1.3 cm), weight (57.9 +/- 0.9 kg),
      and body mass index (21.3 +/- 0.3 kg/m(2)). E(2)-deficient groups had lower (P <
      0.002) E(2) exposure compared with ovulatory groups. Resting systolic BP, HR,
      blood flow, and vascular conductance were lower (P < 0.05) and vascular
      resistance higher (P < 0.05) in LT-E(2) Def compared with both ovulatory groups.
      Peak ischemic blood flow, vascular conductance, and HR were also lower (P < 0.05)
      and vascular resistance higher (P < 0.05) in LT-E(2) Def compared with all other
      groups. Our findings show that exercising women with long-term E(2) deficiency
      have impaired regional blood flow and lower systolic BP and HR compared with
      exercising and sedentary ovulatory women. These cardiovascular alterations
      represent markers of altered vascular function and autonomic regulation of which
      the long-term effects remain unknown.

PMID- 17227960
TI  - Determination of protein replacement rates by deuterated water: validation of
      underlying assumptions.
AB  - H(2)O administration has recently been proposed as a simple and convenient method
      to measure protein synthesis rates. (2)H(2)O administration results in deuterium
      labeling of free amino acids such as alanine, and incorporation into proteins of
      labeled alanine can then be used to measure protein synthesis rates. We examined
      first whether during (2)H(2)O administration plasma free alanine enrichment is a
      correct estimate of the enrichment in the tissue amino acid pools used for
      protein synthesis. We found that, after (2)H(2)O administration, deuterium
      labeling in plasma free alanine equilibrated rapidly with body water, and stable
      enrichment values were obtained within 20 min. Importantly, oral administration
      of (2)H(2)O induced no difference of labeling between portal and peripheral
      circulation except for the initial 10 min after a loading dose. The kinetics of
      free alanine labeling were comparable in various tissues (liver, skeletal muscle,
      heart) and in plasma with identical plateau values. We show next that increased
      glycolytic rate or absorption of unlabeled amino acids from ingested meals do not
      modify alanine labeling. Calculated synthesis rates of mixed proteins were much
      higher (20- to 70-fold) in plasma and liver than in muscle and heart. Last,
      comparable replacement rates of apoB100-VLDL were obtained in humans by using the
      kinetics of incorporation into apoB100 of infused labeled leucine or of alanine
      labeled by (2)H(2)O administration. All of these results support (2)H(2)O as a
      safe, reliable, useful, and convenient tracer for studies of protein synthesis,
      including proteins with slow turnover rate.

PMID- 17227961
TI  - Abnormal muscle and hematopoietic gene expression may be important for clinical
      morbidity in primary hyperparathyroidism.
AB  - In primary hyperparathyroidism (PHPT), excess PTH secretion by adenomatous or
      hyperplastic parathyroid glands leads to elevated serum [Ca(2+)]. Patients
      present complex symptoms of muscular fatigue, various neuropsychiatric,
      neuromuscular, and cardiovascular manifestations, and, in advanced disease,
      kidney stones and metabolic bone disease. Our objective was to characterize
      changes in muscle and hematopoietic gene expression in patients with reversible
      mild PHPT after parathyroidectomy and possibly link molecular pathology to
      symptoms. Global mRNA profiling using Affymetrix gene chips was carried out in
      biopsies obtained before and 1 yr after parathyroidectomy in seven patients
      discovered by routine blood [Ca(2+)] screening. The tissue distribution of PTH
      receptor (PTHR1 and PTHR2) mRNAs were quantitated using real-time RT-PCR in
      unrelated persons to define PTH target tissues. Of about 10,000 expressed genes,
      175 muscle, 169 hematological, and 99 bone-associated mRNAs were affected.
      Notably, the major part of muscle-related mRNAs was increased whereas
      hematological mRNAs were predominantly decreased during disease. Functional and
      molecular network analysis demonstrated major alterations of several tissue
      characteristic groups of mRNAs as well as those belonging to common cell
      signaling and major metabolic pathways. PTHR1 and PTHR2 mRNAs were more
      abundantly expressed in muscle and brain than in hematopoietic cells. We suggest
      that sustained stimulation of PTH receptors present in brain, muscle, and
      hematopoietic cells have to be considered as one independent, important cause of
      molecular disease in PHPT leading to profound alterations in gene expression that
      may help explain symptoms like muscle fatigue, cardiovascular pathology, and
      precipitation of psychiatric illness.

PMID- 17227962
TI  - Response of plasma CNP forms to acute anabolic and catabolic interventions in
      growing lambs.
AB  - Using a novel marker of C-type natriuretic peptide (CNP) synthesis [amino
      terminal pro-CNP (NT-proCNP)], we have recently shown that plasma NT-proCNP is
      strongly correlated with skeletal growth and markers of bone formation and is
      reversibly reduced by glucocorticoids. The effects on CNP of other catabolic or
      anabolic factors, known to affect skeletal growth, are unknown. Accordingly, we
      have studied the response of plasma CNP forms to acute catabolic (caloric
      restriction) and anabolic [growth hormone (GH) stimulation] interventions in
      lambs and related the findings to circulating IGF-I levels, growth velocity, and
      markers of bone formation. Lambs fed a reduced caloric intake (25% of normal) for
      6 days exhibited reduced live weight, plasma urea, and IGF-I (P < 0.001 for all)
      compared with control lambs. Basal levels of NT-proCNP (40.1 +/- 0.9 pmol/l) fell
      promptly to a nadir (28.1 +/- 0.8 pmol/l, P < 0.001) on day 6, returning rapidly
      to basal levels upon refeeding. Although plasma alkaline phosphatase (ALP) fell
      (P < 0.001), reductions in metacarpal growth velocity were not significant within
      the 12-day period of study. In contrast to caloric restriction, long-acting
      bovine recombinant GH (2.5 mg/kg on days 0 and 6), as expected, increased plasma
      IGF-I more than twofold above control for 12 days (P < 0.001). Growth velocity
      did not differ during the 30 days of observation, and, consistent with unchanged
      growth velocity, plasma NT-proCNP and ALP were also unaffected. In conclusion,
      CNP synthesis and markers of bone formation are acutely sensitive to catabolism
      but unaffected by doses of GH that fail to stimulate skeletal growth.

PMID- 17227963
TI  - Differential effects of fasting and leptin on proopiomelanocortin peptides in the
      arcuate nucleus and in the nucleus of the solitary tract.
AB  - The alpha-melanocyte-stimulating hormone (alpha-MSH), derived from
      proopiomelanocortin (POMC), is generated by a posttranslational processing
      mechanism involving the prohormone convertases (PCs) PC1/3 and PC2. In the brain,
      alpha-MSH is produced in the arcuate nucleus (ARC) of the hypothalamus and in the
      nucleus of the solitary tract (NTS) of the medulla. This peptide is key in
      controlling energy balance, as judged by changes observed at transcriptional
      level. However, little information is available regarding the biosynthesis of the
      precursor POMC and the production of its processed peptides during feeding,
      fasting, and fasting plus leptin in the ARC compared with the NTS in conjunction
      with the PC activity. In this study we found that, in the ARC, pomc mRNA, POMC
      derived peptides, and PC1/3 all decreased during fasting, and administration of
      leptin reversed these effects. In contrast, in the NTS, where there is a large
      amount of a 28.1-kDa peptide similar in size to POMC, the 28.1-kDa peptide and
      other POMC-derived peptides, including alpha-MSH, were further accumulated in
      fasting conditions, whereas pomc mRNA decreased. These changes were not reversed
      by leptin. We also observed that, during fasting, PC2 levels decreased in the
      NTS. These data suggest that, in the NTS, fasting induced changes in POMC
      biosynthesis, and processing is independent of leptin. These observations
      indicate that changes in energy status affect POMC in the brain in a tissue
      specific manner. This represents a novel aspect in the regulation of energy
      balance and may have implications in the pathophysiology of obesity.

PMID- 17227964
TI  - Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition
      and oxidative stress generation in adult cardiomyocytes.
AB  - In aerobic conditions, the heart preferentially oxidizes fatty acids. However,
      during metabolic stress, glucose becomes the major energy source, and enhanced
      glucose uptake has a protective effect on heart function and cardiomyocyte
      survival. Thus abnormal regulation of glucose uptake may contribute to the
      development of cardiac disease in diabetics. Ketone bodies are often elevated in
      poorly controlled diabetics and are associated with increased cellular oxidative
      stress. Thus we sought to determine the effect of the ketone body beta
      hydroxybutyrate (OHB) on cardiac glucose uptake during metabolic stress. We used
      2,4-dinitrophenol (DNP), an uncoupler of the mitochondrial oxidative chain, to
      mimic hypoxia in cardiomyocytes. Our data demonstrated that chronic exposure to
      OHB provoked a concentration-dependent decrease of DNP action, resulting in 56%
      inhibition of DNP-mediated glucose uptake at 5 mM OHB. This was paralleled by a
      diminution of DNP-mediated AMP-activated protein kinase (AMPK) and p38 MAPK
      phosphorylation. Chronic exposure to OHB also increased reactive oxygen species
      (ROS) production by 1.9-fold compared with control cells. To further understand
      the role of ROS in OHB action, cardiomyocytes were incubated with H(2)O(2). Our
      results demonstrated that this treatment diminished DNP-induced glucose uptake
      without altering activation of the AMPK/p38 MAPK signaling pathway. Incubation
      with the antioxidant N-acetylcysteine partially restored DNP-mediated glucose but
      not AMPK/p38 MAPK activation. In conclusion, these results suggest that ketone
      bodies, through inhibition of the AMPK/p38 MAPK signaling pathway and ROS
      overproduction, regulate DNP action and thus cardiac glucose uptake. Altered
      glucose uptake in hyperketonemic states during metabolic stress may contribute to
      diabetic cardiomyopathy.

PMID- 17227965
TI  - Knocking down the diencephalic thyrotropin-releasing hormone precursor gene
      normalizes obesity-induced hypertension in the rat.
AB  - We recently showed that diencephalic TRH may mediate the central leptin-induced
      pressor effect. Here, to study the role of TRH in obesity-induced hypertension
      (OIH), we used a model of OIH produced by a high-fat diet (HFD, 45 days) in male
      Wistar rats. After 4 wk, body weight and systolic arterial blood pressure (SABP)
      increased in HFD animals. Plasma leptin was correlated with peritoneal adipose
      tissue. Then, we treated OIH animals with an antisense oligodeoxynucleotide and
      small interfering (si)RNA against the prepro-TRH. Antisense significantly
      decreased diencephalic TRH content and SABP at 24 and 48 h posttreatment. Similar
      effects were observed with siRNA against prepro-TRH but for up to 4 wk.
      Conversely, vehicle, an inverted antisense sequence and siRNA against green
      fluorescence protein, produced no changes. SABP decrease seems to be owing to an
      inhibition of the obesity-enhanced sympathetic outflow but not to an alteration
      in thyroid status. Using a simple OIH model we demonstrated, for the first time,
      that central TRH participates in the hypertension induced by body weight gain
      probably through its well-known action on sympathetic activity. Thus the TRH
      leptin interaction may contribute to the strong association between hypertension
      and obesity.

PMID- 17227966
TI  - The cover. Exotic Landscape.

PMID- 17227967
TI  - Opioid prescriptions soar: increase in legitimate use as well as abuse.

PMID- 17227968
TI  - MRI contrast agents may pose risk for patients with kidney disease.

PMID- 17227969
TI  - Brain scan may predict schizophrenia.

PMID- 17227970
TI  - Fixed-dose unfractionated heparin vs low-molecular-weight heparin for venous
      thromboembolism.

PMID- 17227971
TI  - Fixed-dose unfractionated heparin vs low-molecular-weight heparin for venous
      thromboembolism.

PMID- 17227972
TI  - Fixed-dose unfractionated heparin vs low-molecular-weight heparin for venous
      thromboembolism.

PMID- 17227973
TI  - Fixed-dose unfractionated heparin vs low-molecular-weight heparin for venous
      thromboembolism.

PMID- 17227976
TI  - Increasing medical school matriculation for minority students.

PMID- 17227974
TI  - Raloxifene vs tamoxifen.

PMID- 17227977
TI  - Use of virtual reality simulation for mission rehearsal for carotid stenting.

PMID- 17227978
TI  - Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing
      curative-intent resection of pancreatic cancer: a randomized controlled trial.
AB  - CONTEXT: The role of adjuvant therapy in resectable pancreatic cancer is still
      uncertain, and no recommended standard exists. OBJECTIVE: To test the hypothesis
      that adjuvant chemotherapy with gemcitabine administered after complete resection
      of pancreatic cancer improves disease-free survival by 6 months or more. DESIGN,
      SETTING, AND PATIENTS: Open, multicenter, randomized controlled phase 3 trial
      with stratification for resection, tumor, and node status. Conducted from July
      1998 to December 2004 in the outpatient setting at 88 academic and community
      based oncology centers in Germany and Austria. A total of 368 patients with gross
      complete (R0 or R1) resection of pancreatic cancer and no prior radiation or
      chemotherapy were enrolled into 2 groups. INTERVENTION: Patients received
      adjuvant chemotherapy with 6 cycles of gemcitabine on days 1, 8, and 15 every 4
      weeks (n = 179), or observation ([control] n = 175). MAIN OUTCOME MEASURES:
      Primary end point was disease-free survival, and secondary end points were
      overall survival, toxicity, and quality of life. Survival analysis was based on
      all eligible patients (intention-to-treat). RESULTS: More than 80% of patients
      had R0 resection. The median number of chemotherapy cycles in the gemcitabine
      group was 6 (range, 0-6). Grade 3 or 4 toxicities rarely occurred with no
      difference in quality of life (by Spitzer index) between groups. During median
      follow-up of 53 months, 133 patients (74%) in the gemcitabine group and 161
      patients (92%) in the control group developed recurrent disease. Median disease
      free survival was 13.4 months in the gemcitabine group (95% confidence interval,
      11.4-15.3) and 6.9 months in the control group (95% confidence interval, 6.1-7.8;
      P<.001, log-rank). Estimated disease-free survival at 3 and 5 years was 23.5% and
      16.5% in the gemcitabine group, and 7.5% and 5.5% in the control group,
      respectively. Subgroup analyses showed that the effect of gemcitabine on disease
      free survival was significant in patients with either R0 or R1 resection. There
      was no difference in overall survival between the gemcitabine group (median, 22.1
      months; 95% confidence interval, 18.4-25.8; estimated survival, 34% at 3 years
      and 22.5% at 5 years) and the control group (median, 20.2 months; 95% confidence
      interval, 17-23.4; estimated survival, 20.5% at 3 years and 11.5% at 5 years; P =
      .06, log-rank). CONCLUSIONS: Postoperative gemcitabine significantly delayed the
      development of recurrent disease after complete resection of pancreatic cancer
      compared with observation alone. These results support the use of gemcitabine as
      adjuvant chemotherapy in resectable carcinoma of the pancreas. TRIAL
      REGISTRATION: isrctn.org Identifier: ISRCTN34802808.

PMID- 17227979
TI  - Analysis of observational studies in the presence of treatment selection bias:
      effects of invasive cardiac management on AMI survival using propensity score and
      instrumental variable methods.
AB  - CONTEXT: Comparisons of outcomes between patients treated and untreated in
      observational studies may be biased due to differences in patient prognosis
      between groups, often because of unobserved treatment selection biases.
      OBJECTIVE: To compare 4 analytic methods for removing the effects of selection
      bias in observational studies: multivariable model risk adjustment, propensity
      score risk adjustment, propensity-based matching, and instrumental variable
      analysis. DESIGN, SETTING, AND PATIENTS: A national cohort of 122,124 patients
      who were elderly (aged 65-84 years), receiving Medicare, and hospitalized with
      acute myocardial infarction (AMI) in 1994-1995, and who were eligible for cardiac
      catheterization. Baseline chart reviews were taken from the Cooperative
      Cardiovascular Project and linked to Medicare health administrative data to
      provide a rich set of prognostic variables. Patients were followed up for 7 years
      through December 31, 2001, to assess the association between long-term survival
      and cardiac catheterization within 30 days of hospital admission. MAIN OUTCOME
      MEASURE: Risk-adjusted relative mortality rate using each of the analytic
      methods. RESULTS: Patients who received cardiac catheterization (n = 73 238) were
      younger and had lower AMI severity than those who did not. After adjustment for
      prognostic factors by using standard statistical risk-adjustment methods, cardiac
      catheterization was associated with a 50% relative decrease in mortality (for
      multivariable model risk adjustment: adjusted relative risk [RR], 0.51; 95%
      confidence interval [CI], 0.50-0.52; for propensity score risk adjustment:
      adjusted RR, 0.54; 95% CI, 0.53-0.55; and for propensity-based matching: adjusted
      RR, 0.54; 95% CI, 0.52-0.56). Using regional catheterization rate as an
      instrument, instrumental variable analysis showed a 16% relative decrease in
      mortality (adjusted RR, 0.84; 95% CI, 0.79-0.90). The survival benefits of
      routine invasive care from randomized clinical trials are between 8% and 21%.
      CONCLUSIONS: Estimates of the observational association of cardiac
      catheterization with long-term AMI mortality are highly sensitive to analytic
      method. All standard risk-adjustment methods have the same limitations regarding
      removal of unmeasured treatment selection biases. Compared with standard
      modeling, instrumental variable analysis may produce less biased estimates of
      treatment effects, but is more suited to answering policy questions than specific
      clinical questions.

PMID- 17227980
TI  - Risk factors for early myocardial infarction in South Asians compared with
      individuals in other countries.
AB  - CONTEXT: South Asians have high rates of acute myocardial infarction (AMI) at
      younger ages compared with individuals from other countries but the reasons for
      this are unclear. OBJECTIVE: To evaluate the association of risk factors for AMI
      in native South Asians, especially at younger ages, compared with individuals
      from other countries. DESIGN, SETTING, AND PARTICIPANTS: Standardized case
      control study of 1732 cases with first AMI and 2204 controls matched by age and
      sex from 15 medical centers in 5 South Asian countries and 10,728 cases and
      12,431 controls from other countries. Individuals were recruited to the study
      between February 1999 and March 2003. MAIN OUTCOME MEASURE: Association of risk
      factors for AMI. RESULTS: The mean (SD) age for first AMI was lower in South
      Asian countries (53.0 [11.4] years) than in other countries (58.8 [12.2] years;
      P<.001). Protective factors were lower in South Asian controls than in controls
      from other countries (moderate- or high-intensity exercise, 6.1% vs 21.6%; daily
      intake of fruits and vegetables, 26.5% vs 45.2%; alcohol consumption > or
      =once/wk, 10.7% vs 26.9%). However, some harmful factors were more common in
      native South Asians than in individuals from other countries (elevated
      apolipoprotein B(100) /apolipoprotein A-I ratio, 43.8% vs 31.8%; history of
      diabetes, 9.5% vs 7.2%). Similar relative associations were found in South Asians
      compared with individuals from other countries for the risk factors of current
      and former smoking, apolipoprotein B100/apolipoprotein A-I ratio for the top vs
      lowest tertile, waist-to-hip ratio for the top vs lowest tertile, history of
      hypertension, history of diabetes, psychosocial factors such as depression and
      stress at work or home, regular moderate- or high-intensity exercise, and daily
      intake of fruits and vegetables. Alcohol consumption was not found to be a risk
      factor for AMI in South Asians. The combined odds ratio for all 9 risk factors
      was similar in South Asians (123.3; 95% confidence interval [CI], 38.7-400.2] and
      in individuals from other countries (125.7; 95% CI, 88.5-178.4). The similarities
      in the odds ratios for the risk factors explained a high and similar degree of
      population attributable risk in both groups (85.8% [95% CI, 78.0%-93.7%] vs 88.2%
      [95% CI, 86.3%-89.9%], respectively). When stratified by age, South Asians had
      more risk factors at ages younger than 60 years. After adjusting for all 9 risk
      factors, the predictive probability of classifying an AMI case as being younger
      than 40 years was similar in individuals from South Asian countries and those
      from other countries. CONCLUSION: The earlier age of AMI in South Asians can be
      largely explained by higher risk factor levels at younger ages.

PMID- 17227981
TI  - Palliative management of fatigue at the close of life: "it feels like my body is
      just worn out".
AB  - Fatigue is the most common chronic symptom associated with cancer and other
      chronic progressive diseases. The assessment and treatment of fatigue at or near
      the end of life can be complex. Some of the challenges include its subjective
      nature, with great variability in its source, how it is expressed, and how it is
      perceived, requiring treatment to be based on patient report of frequency and
      severity; its multidimensional character; and the limited understanding of its
      pathophysiology. Using the case of an 82-year-old retired nurse with fatigue that
      could be explained by a number of concurrent conditions, including anemia, weight
      loss, depression and isolation, dyspnea, deconditioning, and medications, the
      authors illustrate the clinical approach to assess and treat fatigue at the end
      of life.

PMID- 17227982
TI  - End-of-life care for homeless patients: "she says she is there to help me in any
      situation".

PMID- 17227983
TI  - The role of litigation in defining drug risks.

PMID- 17227984
TI  - Adjuvant therapy for pancreatic cancer: one small step forward.

PMID- 17227985
TI  - Estimating treatment effects using observational data.

PMID- 17227986
TI  - JAMA patient page. Pancreatic cancer.

PMID- 17227987
TI  - Response rate as an endpoint in clinical trials.

PMID- 17227988
TI  - Calcium supplementation and prevention of colorectal neoplasia: lessons from
      clinical trials.

PMID- 17227991
TI  - Personal mouse colonies give hope for pancreatic cancer patients.

PMID- 17227990
TI  - Institute of Medicine, Congress seek solutions to FDA's safety woes through
      reform, funding.

PMID- 17227992
TI  - Stat bite: Pancreatic cancer by stage.

PMID- 17227989
TI  - Prevention of gastric cancer: a miss.

PMID- 17227993
TI  - Adaptive design may hasten clinical trials.

PMID- 17227994
TI  - Researchers tackle metastasis, cancer's last frontier.

PMID- 17227995
TI  - Improvement in histologic response but not survival in osteosarcoma patients
      treated with intensified chemotherapy: a randomized phase III trial of the
      European Osteosarcoma Intergroup.
AB  - BACKGROUND: Previous randomized controlled trials that used the two-drug
      chemotherapy regimen of cisplatin and doxorubicin as the conventional arm showed
      no evidence of benefit from an increase in the number of agents or the length of
      treatment. It was then proposed that survival could be improved by increasing the
      planned dose intensity of cisplatin and doxorubicin. METHODS: Previously
      untreated patients with nonmetastatic, high-grade, central osteosarcoma of an
      extremity were randomly assigned to Regimen-C (conventional treatment with six 3
      week cycles of cisplatin [100 mg/m2 by 24-hour infusion] and doxorubicin [25
      mg/m2/day by 4-hour infusion for 3 days]) or to Regimen-DI (intensified treatment
      with identical total doses of cisplatin and doxorubicin, planned as six 2-week
      cycles supported by granulocyte colony stimulating factor (G-CSF). Surgery was
      scheduled for week 6 in both arms. Primary and secondary outcome measures were
      overall and progression-free survival, respectively. Intention-to-treat analyses
      were performed using standard survival analysis methods. Landmark analyses were
      performed in patients with known surgical details and centrally reviewed
      histologic response. All statistical tests were two-sided. RESULTS: Between May
      1993 and September 2002, treatment was randomly allocated to 497 eligible
      patients. Six cycles of chemotherapy were completed by 78% of patients in Regimen
      C and 80% of patients in Regimen-DI. The delivered preoperative median dose
      intensity of cisplatin was 86% in Regimen-C and 111% in Regimen-DI (as the
      percentage of that planned for the conventional regimen). Postoperative median
      dose intensity of cisplatin was 82% in Regimen-C and 110% in Regimen-DI (the
      corresponding figures for doxorubicin dose intensity were similar). Regimen-DI
      was associated with lower risks of severe leucopenia and neutropenia and higher
      risks of thrombocytopenia and mucositis. Good histologic response (>90% tumor
      necrosis) was observed in 36% of Regimen-C patients and 50% of Regimen-DI
      patients (P = .003, chi2 test). There was no evidence of a difference in overall
      survival (hazard ratio [HR] = 0.94, 95% CI = 0.71 to 1.24; P = .64) or
      progression-free survival (HR = 0.98, 95% CI = 0.77 to 1.24; P = .83). Landmark
      analyses showed similar results. CONCLUSIONS: Planned intensification of
      chemotherapy with cisplatin and doxorubicin increased received dose intensity and
      resulted in a statistically significant increase in favorable histologic response
      rate, but not in increased progression-free or overall survival. Our results call
      into question the use of histologic response as a surrogate outcome measure in
      trials of this disease.

PMID- 17227996
TI  - Prolonged effect of calcium supplementation on risk of colorectal adenomas in a
      randomized trial.
AB  - BACKGROUND: Calcium supplementation has been shown to decrease the risk of
      recurrence of colorectal adenomas in randomized trials. However, the duration of
      this protective effect after cessation of active supplementation is not known.
      METHODS: In the Calcium Polyp Prevention Study, 930 subjects with a previous
      colorectal adenoma were randomly assigned from November 1988 through April 1992
      to receive placebo or 1200 mg of elemental calcium daily for 4 years. The Calcium
      Follow-up Study was an observational phase of the trial that tracked adenoma
      occurrence for an average of 7 years after the end of randomized treatment and
      gathered information regarding the use of medications, vitamins, and supplements
      during that time. We obtained follow-up information for 822 subjects, 597 of whom
      underwent at least one colonoscopy after the end of study treatment and are
      included in this analysis. Generalized linear models were used to compute
      relative risks (RRs) and 95% confidence intervals (CIs) for the effect of
      randomized calcium treatment on risk of adenoma recurrence during the first 5
      years after study treatment ended and during the subsequent 5 years. Statistical
      tests were two-sided. RESULTS: During the first 5 years after randomized
      treatment ended, subjects in the calcium group still had a substantially and
      statistically significantly lower risk of any adenoma than those in the placebo
      group (31.5% versus 43.2%; adjusted RR = 0.63, 95% CI = 0.46 to 0.87, P = .005)
      and a smaller and not statistically significant reduction in risk of advanced
      adenomas (adjusted RR = 0.85, 95% CI = 0.43 to 1.69, P = .65). However, the
      randomized treatment was not associated with the risk of any type of polyp during
      the next 5 years. The findings were broadly similar when the analysis was
      restricted to subjects who did not report use of any calcium supplements after
      the treatment phase of the trial ended. CONCLUSION: The protective effect of
      calcium supplementation on risk of colorectal adenoma recurrence extends up to 5
      years after cessation of active treatment, even in the absence of continued
      supplementation.

PMID- 17227997
TI  - Chemoprevention of precancerous gastric lesions with antioxidant vitamin
      supplementation: a randomized trial in a high-risk population.
AB  - BACKGROUND: Gastric cancer is one of the most common malignancies worldwide.
      Histopathologic studies have identified a sequence of changes in the gastric
      mucosa that mark the slow progression from normal tissue to carcinoma.
      Epidemiologic evidence suggests that a diet rich in fresh fruit and vegetables
      could be a protective factor against this disease. This effect may be mediated
      through antioxidant vitamins. METHODS: A randomized, double-blind chemoprevention
      trial was conducted among 1980 subjects in Tachira State, Venezuela (whose
      population is at high risk for gastric cancer), to determine the effect of
      dietary supplementation with vitamin C, vitamin E, and beta-carotene on the
      progression and regression of precancerous gastric lesions. Subjects were
      randomly assigned to receive either a combination of vitamin C (750 mg/day),
      vitamin E (600 mg/day), and beta-carotene (18 mg/day) or placebo for 3 years.
      Changes in the gastric mucosa were determined by histologic diagnosis based on
      five biopsies taken from prespecified areas of the stomach at baseline and
      annually for 3 years. All biopsies were reviewed by a single expert pathologist.
      Progression rates (and regression rates) were calculated by comparing the first
      and last available gastroscopies for each subject and dividing the number of
      subjects whose diagnoses increased (decreased) in severity by the total follow-up
      time. Overall rate ratios were calculated by Poisson regression, controlling for
      baseline diagnosis. All statistical tests were two-sided. RESULTS: Median plasma
      vitamin levels were increased in the treatment group between baseline and 1 year
      after randomization from 0.43 micromol/L (interquartile range [IQR] = 0.26-0.69)
      to 2.89 micromol/L (IQR = 1.76-4.22) for beta-carotene, from 26.7 micromol/L (IQR
      = 23.1-31.2) to 54.9 micromol/L (IQR = 42.8-67.6) for alpha-tocopherol, and from
      47.70 micromol/L (IQR = 36.9-58.5) to 61.9 micromol/L (IQR = 52.2-72.7) for
      vitamin C. Overall progression rates per 100 person-years were 74.3 in the
      placebo group and 67.8 in the group randomly assigned to vitamins. Overall
      regression rates were 109.4 in the placebo group and 116.5 in the group randomly
      assigned to vitamins. There was no statistically significant difference in
      progression rate (rate ratio = 0.92, 95% confidence interval [CI] = 0.74 to 1.15)
      or regression rate (rate ratio = 1.09, 95% CI = 0.90 to 1.33) between vitamin and
      placebo groups. CONCLUSION: Supplementation with antioxidant micronutrients is
      not an effective tool for gastric cancer control in this high-risk population.
      The results of this trial are consistent with previous findings on the lack of
      effect of nutritional supplementation on precancerous gastric lesions.

PMID- 17227998
TI  - Critical review of published microarray studies for cancer outcome and guidelines
      on statistical analysis and reporting.
AB  - BACKGROUND: Both the validity and the reproducibility of microarray-based
      clinical research have been challenged. There is a need for critical review of
      the statistical analysis and reporting in published microarray studies that focus
      on cancer-related clinical outcomes. METHODS: Studies published through 2004 in
      which microarray-based gene expression profiles were analyzed for their relation
      to a clinical cancer outcome were identified through a Medline search followed by
      hand screening of abstracts and full text articles. Studies that were eligible
      for our analysis addressed one or more outcomes that were either an event
      occurring during follow-up, such as death or relapse, or a therapeutic response.
      We recorded descriptive characteristics for all the selected studies. A critical
      review of outcome-related statistical analyses was undertaken for the articles
      published in 2004. RESULTS: Ninety studies were identified, and their descriptive
      characteristics are presented. Sixty-eight (76%) were published in journals of
      impact factor greater than 6. A detailed account of the 42 studies (47%)
      published in 2004 is reported. Twenty-one (50%) of them contained at least one of
      the following three basic flaws: 1) in outcome-related gene finding, an unstated,
      unclear, or inadequate control for multiple testing; 2) in class discovery, a
      spurious claim of correlation between clusters and clinical outcome, made after
      clustering samples using a selection of outcome-related differentially expressed
      genes; or 3) in supervised prediction, a biased estimation of the prediction
      accuracy through an incorrect cross-validation procedure. CONCLUSIONS: The most
      common and serious mistakes and misunderstandings recorded in published studies
      are described and illustrated. Based on this analysis, a proposal of guidelines
      for statistical analysis and reporting for clinical microarray studies, presented
      as a checklist of "Do's and Don'ts," is provided.

PMID- 17227999
TI  - Atopy and risk of non-Hodgkin lymphoma.
AB  - BACKGROUND: A possible connection between allergy and cancer has been suspected,
      but allergy-related conditions or atopy have been inconsistently associated with
      reduced risks of non-Hodgkin lymphoma. We investigated this association in a
      population-based case-control study and in a prospective study with prediagnostic
      blood specimens. METHODS: We carried out a population-based study of 3055 case
      patients with non-Hodgkin lymphoma and 3187 control subjects in Denmark and
      Sweden, including questionnaire information on allergy and blood specimens, and a
      nested case-control study within a prospective cohort of more than 400,000
      Finnish women. In the second study, serum specimens from the 198 case patients
      who developed non-Hodgkin lymphoma within a median of 8.9 years after the blood
      was drawn were matched with serum specimens from 594 control subjects. In both
      studies, laboratory-based evidence of allergy (atopy) was determined in serum on
      the basis of specific IgE reactivity to common inhalant allergens. Dissemination
      of disease was classified by the Ann Arbor system. Odds ratios (ORs) with 95%
      confidence intervals (CIs) were calculated by logistic regression. RESULTS: In
      the first study, ever having hay fever, but not other allergic conditions, was
      associated with a reduced risk of non-Hodgkin lymphoma. In particular, subjects
      with specific IgE reactivity in serum had a 32% (95% CI = 20% to 42%) lower risk
      of overall non-Hodgkin lymphoma than those without such reactivity. However,
      among case patients, dissemination of the disease was strongly inversely
      associated with specific IgE reactivity. In the second (i.e., prospective) study,
      no association was found between non-Hodgkin lymphoma and specific IgE
      reactivity, except possibly immediately before a diagnosis of non-Hodgkin
      lymphoma (> or = 10 years before diagnosis, OR = 1.00, 95% CI = 0.48 to 2.09; 5-9
      years before, OR = 0.95, 95% CI = 0.50 to 1.84; 1-4 years before, OR = 0.33, 95%
      CI = 0.11 to 1.02; and < 1 year before, OR = 0.27, 95% CI = 0.03 to 2.31).
      CONCLUSION: Allergy may not be causally associated with the risk of non-Hodgkin
      lymphoma. The inverse association observed in some case-control studies may arise
      because non-Hodgkin lymphoma suppresses the immunologic response to allergens.

PMID- 17228000
TI  - Prognostic value of Ki67 expression after short-term presurgical endocrine
      therapy for primary breast cancer.
AB  - Tumor expression of the proliferation antigen Ki67 is widely used to assess the
      prognosis of cancer patients. A change in the expression of Ki67 after short-term
      exposure of patients to therapeutic agents is frequently used as a
      pharmacodynamic marker of efficacy, particularly among breast cancer patients
      before undergoing surgery. To determine the clinical significance of the level of
      tumor cell proliferation during endocrine therapy for breast cancer, we measured
      the expression of Ki67 in tumor biopsy samples taken before and after 2 weeks of
      presurgical treatment with anastrozole or tamoxifen or the combination of
      anastrozole plus tamoxifen in 158 patients with hormone receptor-positive primary
      disease. In a multivariable analysis, we found that higher Ki67 expression after
      2 weeks of endocrine therapy was statistically significantly associated with
      lower recurrence-free survival (P = .004) whereas higher Ki67 expression at
      baseline was not. Larger baseline tumor size and lower estrogen receptor level
      after 2 weeks of treatment were also statistically significantly associated with
      poorer recurrence-free survival (P < .001 and P = .04, respectively). Our data
      indicate that measurements of tumor Ki67 level after short-term endocrine
      treatment may improve the prediction of recurrence-free survival by integrating
      the prognostic value of Ki67 level at baseline with changes in Ki67 level that
      are associated with treatment benefit.

PMID- 17228001
TI  - A prospective study of periodontal disease and pancreatic cancer in US male
      health professionals.
AB  - Two previous cohort studies reported positive associations between tooth loss or
      periodontitis and pancreatic cancer risk. Data on periodontal disease were
      obtained at baseline and every other year thereafter in a cohort of 51,529 male
      health professionals aged 40-75 years. A total of 216 patients were diagnosed
      with incident pancreatic cancer during 16 years of follow-up. Multivariable
      relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox
      proportional hazards models controlling for potential confounders, including
      detailed smoking history. All statistical tests were two-sided. Compared with no
      periodontal disease, history of periodontal disease was associated with increased
      pancreatic cancer risk (overall, multivariable RR = 1.64, 95% CI = 1.19 to 2.26;
      P = .002; crude incidence rates: 61 versus 25 per 100,000 person-years; among
      never smokers, multivariable RR = 2.09, 95% CI = 1.18 to 3.71; P = .01; crude
      incidence rates: 61 versus 19 per 100,000 person-years). In contrast, baseline
      number of natural teeth and cumulative tooth loss during follow-up were not
      strongly associated with pancreatic cancer. The association between periodontal
      disease and increased risk of pancreatic cancer may occur through plausible
      biologic mechanisms, but confirmation of this association is necessary.

PMID- 17228003
TI  - Re: Survival with aromatase inhibitors and inactivators versus standard hormonal
      therapy in advanced breast cancer: meta-analysis.

PMID- 17228004
TI  - Cutaneous recall phenomenon at the site of previous doxorubicin extravasation
      after second-line chemotherapy.

PMID- 17228005
TI  - Images in cardiovascular medicine. Electrocardiogram, echocardiography, and
      magnetic resonance imaging characteristics in Uhl's disease.

PMID- 17228006
TI  - Images in cardiovascular medicine. Magnetic resonance imaging of a posttraumatic
      myocardial infarction and ventricular septal defect with a closure device in
      place.

PMID- 17228007
TI  - Images in cardiovascular medicine. Sinus of Valsalva aneurysm with right
      ventricular outflow tract obstruction: evaluation with Doppler, real-time 3
      dimensional and contrast echocardiography.

PMID- 17228008
TI  - Letter by Ben-Dov and Bursztyn regarding article, "Role of diuretics in the
      prevention of heart failure: the Antihypertensive and Lipid-Lowering Treatment to
      Prevent Heart Attack Trial".

PMID- 17228009
TI  - Viewpoint: pharmaceutical innovation in Europe.

PMID- 17228010
TI  - The cardiovascular world is definitely not flat.

PMID- 17228011
TI  - Cardiac resynchronization therapy in New York Heart Association class IV heart
      failure: it is all about selection.

PMID- 17228012
TI  - Is renal artery stenting the correct treatment of renal artery stenosis? The case
      for renal artery stenting for treatment of renal artery stenosis.

PMID- 17228013
TI  - Is renal artery stenting the correct treatment of renal artery stenosis? Case
      against angioplasty and stenting of atherosclerotic renal artery stenosis.

PMID- 17228014
TI  - Ebstein's anomaly.

PMID- 17228015
TI  - Role of radiation therapy in localized aggressive lymphoma.

PMID- 17228016
TI  - Clinical uses of microsatellite instability testing in colorectal cancer: an
      ongoing challenge.

PMID- 17228017
TI  - Mind your elders: therapeutic implications of epidermal growth factor receptor
      inhibition in older patients with advanced non-small-cell lung cancer.

PMID- 17228018
TI  - Cisplatin-induced long-term hearing impairment is associated with specific
      glutathione s-transferase genotypes in testicular cancer survivors.
AB  - PURPOSE: Cisplatin, a cornerstone of combination chemotherapy in the treatment of
      testicular cancer, induces hearing impairment with considerable interindividual
      variations. These differences might be a result of functional polymorphisms in
      cisplatin-detoxifying enzymes like glutathione S-transferases (GSTs). PATIENTS
      AND METHODS: We identified 173 cisplatin-treated testicular cancer survivors
      (TCSs) who had participated in a long-term survey that included audiometric
      testing and lymphocyte sampling. The hearing decibel thresholds at 4,000 Hz were
      categorized into leveled scales by normative decibel percentiles. Known
      functional polymorphisms (positive or negative) in GSTT1 and GSTM1 and codon 105
      A/G (Ile/Val) in GSTP1 were analyzed by multiplex polymerase chain reaction,
      followed by restriction enzyme cutting, and separated by gel electrophoresis.
      RESULTS: The risk of having an inferior audiometric result was more than four
      times higher in TCSs with 105Ile/105Ile-GSTP1 or 105Val/105Ile-GSTP1 compared
      with 105Val/105Val-GSTP1 (odds ratio [OR] = 4.21; 95% CI, 1.99 to 8.88; P < .001
      when modeled by ordinal logistic regression [OLR]). GSTM1 positivity was
      detrimental for hearing ability. Two combined genotypes were associated with
      hearing ability. The presence of pattern 1 (GSTT1 positive, GSTM1 positive, and
      105Ile/105Ile-GSTP1) was associated with hearing impairment (OR = 2.76; 95% CI,
      1.35 to 5.64; P = .005, OLR). TCSs with pattern 2 (GSTT1 positive, GSTM1
      positive, and 105Val/105Val-GSTP1) had better hearing ability than TCSs without
      this pattern (OR = 5.35; 95% CI, 2.25 to 12.76; P < .001, OLR). CONCLUSION: The
      presence of both alleles of 105Val-GSTP1 offered protection against cisplatin
      induced hearing impairment. Two genotype patterns with good and poor protection
      against cisplatin-induced ototoxicity were identified.

PMID- 17228019
TI  - Phase II clinical trial of chemotherapy-naive patients > or = 70 years of age
      treated with erlotinib for advanced non-small-cell lung cancer.
AB  - PURPOSE: This is a phase II, multicenter, open-label study of chemotherapy-naive
      patients with non-small-cell lung cancer (NSCLC) and age > or = 70 years who were
      treated with erlotinib and evaluated to determine the median, 1-year, and 2-year
      survival. The secondary end points include radiographic response rate, time to
      progression (TTP), toxicity, and symptom improvement. PATIENTS AND METHODS:
      Eligible patients with NSCLC were treated with erlotinib 150 mg/d until disease
      progression or significant toxicity. Tumor response was assessed every 8 weeks by
      computed tomography scan using Response Evaluation Criteria in Solid Tumors.
      Tumor samples were analyzed for the presence of somatic mutations in EGFR and
      KRAS. RESULTS: Eighty eligible patients initiated erlotinib therapy between March
      2003 and May 2005. There were eight partial responses (10%), and an additional 33
      patients (41%) had stable disease for 2 months or longer. The median TTP was 3.5
      months (95% CI, 2.0 to 5.5 months). The median survival time was 10.9 months (95%
      CI, 7.8 to 14.6 months). The 1- and 2- year survival rates were 46% and 19%,
      respectively. The most common toxicities were acneiform rash (79%) and diarrhea
      (69%). Four patients developed interstitial lung disease of grade 3 or higher,
      with one treatment-related death. EGFR mutations were detected in nine of 43
      patients studied. The presence of an EGFR mutation was strongly correlated with
      disease control, prolonged TTP, and survival. CONCLUSION: Erlotinib monotherapy
      is active and relatively well tolerated in chemotherapy-naive elderly patients
      with advanced NSCLC. Erlotinib merits consideration for further investigation as
      a first-line therapeutic option in elderly patients.

PMID- 17228020
TI  - Partially matched, nonmyeloablative allogeneic transplantation: clinical outcomes
      and immune reconstitution.
AB  - PURPOSE: Allogeneic transplantation is typically limited to younger patients
      having a matched donor. To allow a donor to be found for nearly all patients, we
      have used a nonmyeloablative conditioning regimen in conjunction with stem cells
      from a related donor with one fully mismatched HLA haplotype. PATIENTS AND
      METHODS: Fludarabine, cyclophosphamide, and alemtuzumab were used as the
      preparatory regimen. Additional graft-versus-host disease (GVHD) prophylaxis
      included mycophenolate with or without cyclosporine. Patients with persistence of
      disease had a donor lymphocyte boost planned. Toxicities, engraftment, response,
      survival, and immune recovery are reported. RESULTS: Forty-nine patients with
      hematologic malignancies or marrow failure and no other available donors were
      enrolled. Ninety-four percent of patients had successful engraftment, and 8% had
      secondary graft failure. The treatment-related mortality rate was 10.2%, and 8%
      of patients had severe GVHD. Encouraging evidence of quantitative lymphocyte
      recovery through expansion of transplanted T cells was noted by 3 to 6 months.
      Seventy-five percent of patients attained a complete remission, and 1-year
      survival rate was 31% (95% CI, 18% to 44%). A standard-risk group of 19 patients
      with aplasia or in remission at transplantation demonstrated a 63% 1-year
      survival rate (95% CI, 38% to 80%) and 2.9-year median overall survival time (95%
      CI, 6.2 to 48 months). CONCLUSION: Nonmyeloablative therapy using haploidentical
      family member donors is feasible because the main obstacles of GVHD and graft
      rejection are manageable, allowing readily available stem-cell donors to be found
      for nearly all patients. Further qualitative and quantitative improvement in
      immune recovery is needed to address the high rate of relapse and risk of severe
      infections.

PMID- 17228021
TI  - CHOP alone compared with CHOP plus radiotherapy for localized aggressive lymphoma
      in elderly patients: a study by the Groupe d'Etude des Lymphomes de l'Adulte.
AB  - PURPOSE: Chemoradiotherapy has been considered standard treatment for patients
      with limited-stage aggressive lymphoma on the basis of trials conducted before
      the introduction of the International Prognostic Index. To evaluate this approach
      in elderly patients with low-risk localized lymphoma, we conducted a trial
      comparing chemoradiotherapy with chemotherapy alone. PATIENTS AND METHODS:
      Previously untreated patients older than 60 years with localized stage I or II
      histologically aggressive lymphoma and no adverse prognostic factors of the
      International Prognostic Index were randomly assigned to receive either four
      cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus
      involved-field radiotherapy (299 patients) or chemotherapy alone with four cycles
      of CHOP (277 patients). RESULTS: With a median follow-up time of 7 years, event
      free and overall survival did not differ between the two treatment groups (P = .6
      and P = .5, respectively). The 5-year estimates of event-free survival were 61%
      for patients receiving chemotherapy alone and 64% for patients receiving CHOP
      plus radiotherapy; the 5-year estimates of overall survival were 72% and 68%,
      respectively. In a multivariate analysis, overall survival was affected by stage
      II disease (P < .001) and male sex (P = .03). CONCLUSION: In this large
      prospective study, CHOP plus radiotherapy did not provide any advantage over CHOP
      alone for the treatment of low-risk localized aggressive lymphoma in elderly
      patients.

PMID- 17228022
TI  - Clinicopathologic and pedigree differences in amsterdam I-positive hereditary
      nonpolyposis colorectal cancer families according to tumor microsatellite
      instability status.
AB  - PURPOSE: To establish the clinicopathologic and familial differences within
      Amsterdam I-positive families, showing either tumor microsatellite instability
      (MSI) or microsatellite stability (MSS) in order to confirm or deny the existence
      of hereditary nonpolyposis colorectal cancer (HNPCC) without defects in the
      mismatch repair system. PATIENTS AND METHODS: Sixty-four Amsterdam I-positive
      families were included in the study for which full, three-generation, family
      medical histories and colorectal paraffin-embedded tumors were obtained. Both
      personal and clinicopathologic information of patients were collected. In all
      cases, both the MSI status and the mismatch repair (MMR) protein expression were
      analyzed. MMR genetic testing was performed on the MSI families. RESULTS: Of the
      Amsterdam I-positive families, 59.4% were tumor MSI, and 40.6% were tumor MSS.
      When comparing both groups, the statistical differences were observed in the age
      of onset (MSI, 41 years; MSS, 53 years); in the colorectal tumor location, more
      frequently proximal in MSI cases; in fewer mucinous tumors in MSS; and loss of
      MMR protein expression in the MSI tumors. Regarding the individual and familial
      cancer history, we observed a predominance of individuals with multiple primary
      tumors in MSI pedigrees, as well as differences in the type of tumors developed
      within the family. CONCLUSION: Our findings support the suspicion of another
      hereditary colorectal syndrome different from HNPCC and characterized by MSS, the
      normal MMR immunohistochemical expression, the presence of only colorectal
      tumors, and the absence of individuals with multiple primary tumors. All these
      circumstances suggest the existence of a non-MMR gene being responsible for this
      new syndrome.

PMID- 17228024
TI  - The Q121/Q121 genotype of ENPP1/PC-1 is associated with lower BMI in non-diabetic
      whites.
AB  - This study investigated the role of the ENPP1/PC-1 gene K121Q polymorphism in
      predicting BMI (kg/m2) in non-diabetic individuals. Three independent samples (n
      = 631, n = 304, and n = 505) of adult whites were analyzed. Selection criteria
      were fasting plasma glucose level <126 mg/dL, absence of severe obesity (BMI > or
      =40 kg/m2), and lack of treatment known to modulate BMI. In Sample 1, BMI values
      were different in individuals carrying the K121/K121 (KK), K121/Q121 (KQ), and
      Q121/Q121 (QQ) genotypes (25.5 +/- 4.3, 25.3 +/- 4.1, and 22.8 +/- 2.5 kg/m2,
      respectively (adjusted p = 0.022); BMI values in Samples 2 and 3 also tended to
      be different, although the differences, after adjustment for age and sex, did not
      reach statistical significance. When data were pooled, BMI values were 25.8 +/-
      4.4, 25.6 +/- 4.4, and 23.6 +/- 3.3 kg/m2 in KK, KQ, and QQ individuals (adjusted
      p = 0.029). According to a recessive model, QQ individuals had lower BMI values
      than KK and KQ individuals combined (23.6 +/- 3.3 kg/m2 vs. 25.7 +/- 4.4 kg/m2;
      adjusted p = 0.008). These data suggest that the QQ genotype of the ENPP1/PC-1
      gene is associated with lower BMI. If similar results are confirmed in
      prospective studies, the K121Q polymorphism may help identify people at risk for
      obesity.

PMID- 17228023
TI  - Prognostic and predictive roles of high-degree microsatellite instability in
      colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and
      Bowel Project Collaborative Study.
AB  - PURPOSE: The role of high-degree microsatellite instability (MSI-H) as a marker
      to predict benefit from adjuvant chemotherapy remains unclear. PATIENTS AND
      METHODS: To help define its impact, we conducted an analysis of National Surgical
      Adjuvant Breast and Bowel Project (NSABP) patients who were randomly assigned to
      a surgery-alone group (untreated cohort) and patients assigned to an adjuvant
      fluorouracil (FU) -treated group (treated cohort). MSI-H and other potential
      markers were assessed (TGF-BRII, p53, thymidylate synthase, and Ki67). RESULTS:
      In all, 98 (18.1%) of 542 patients exhibited MSI-H, and there was a strong
      inverse relationship between MSI-H and mutant p53 status (P < .001). The
      prognostic analyses showed increased recurrence-free survival (RFS) for MSI-H
      patients versus MSS/MSI-L patients (P = .10), but showed no difference in overall
      survival (OS; P = .67). There was a potential interaction between MSI-H and
      mutant p53 in terms of improved RFS (P = .03). In the predictive marker analysis,
      we observed no interaction between MSI status and treatment for either RFS (P =
      .68) or OS (P = .62). Hazard ratios (HR) for RFS for MSI-H versus MSS/MSI-L
      patients were 0.77 (95% CI, 0.40 to 1.48) in the untreated-patients group and
      0.60 (95% CI, 0.30 to 1.19) in the treated-patients group. HRs for OS were 0.82
      (95% CI, 0.44 to 1.51) and 1.02 (95% CI, 0.56 to 1.85) for the respective groups.
      There was a trend toward improved RFS in patients with MSI-H and mutant p53.
      CONCLUSION: These results do not support the use of MSI-H as a predictive marker
      of chemotherapy benefit.

PMID- 17228025
TI  - The SH2B gene is associated with serum leptin and body fat in normal female
      twins.
AB  - Src-homology-2 (SH2)-B, a Janus tyrosine kinase 2-interacting protein, has been
      identified recently as a key regulator of leptin and insulin sensitivity, glucose
      homeostasis, and body weight in mice. The aim of this study was to determine
      whether single-nucleotide polymorphisms (SNPs) in the human SH2B gene are
      associated with these variables. A tagging SNP (tSNP), Ala484Thr (rs7498665), was
      selected to represent five common SNPs (minor allele frequency > 0.05) in perfect
      linkage disequilibrium in a 16-kb region encompassing the SH2B gene. The tSNP was
      genotyped in 2455 white female twins (mean age, 47.4 +/- 12.6 years) from the St.
      Thomas' United Kingdom Adult Twin Registry (Twins United Kingdom). Ala484Thr
      (minor allele frequency, 0.38) was associated with serum leptin, total fat, waist
      circumference, and body weight (P = 0.02 to 0.04). The coding SNP has no
      predicted effect on protein structure or function and is likely to be in linkage
      disequilibrium with an as-yet unidentified functional variant in the SH2B gene.
      Our results support a role for SH2-B in modulating the regulation of body weight
      and fat by leptin in this female population. If SH2-B signaling is attenuated in
      diet-induced obesity, it could become a target for drug-induced leptin
      sensitization.

PMID- 17228026
TI  - Prevalence and risk factors of overweight and obesity in China.
AB  - OBJECTIVE: To examine the prevalence and risk factors of overweight and obesity
      in China. RESEARCH METHODS AND PROCEDURES: A cross-sectional survey was conducted
      in a nationally representative sample of 15,540 Chinese adults in 2000-2001. Body
      weight, height, and waist circumference were measured by trained observers.
      Overweight and obesity were defined according to the World Health Organization
      classification. Central obesity was defined according to guidelines of the
      International Diabetes Federation. RESULTS: Mean BMI and waist circumference were
      23.1 kg/m2 and 79.6 cm, respectively, for men and 23.5 kg/m2 and 77.2 cm,
      respectively, for women. The prevalences of overweight and obesity were 24.1% and
      2.8% in men and 26.1% and 5.0% in women, respectively. The prevalence of central
      obesity was 16.1% in men and 37.6% in women. The prevalences of overweight,
      obesity, and central obesity were higher among residents in northern China
      compared with their counterparts in southern China and among those in urban areas
      compared with those in rural areas. Lifestyle factors were the most important
      risk factors to explain the differences in overweight and central obesity between
      northern and southern residents. Among women, lifestyle and diet were the most
      important risk factors to explain the differences between urban and rural
      residents, whereas socioeconomic status, lifestyle, and diet were all important
      among men. DISCUSSION: Our study indicates that overweight and obesity have
      become important public health problems in China. Environmental risk factors may
      be the main reason for regional differences in the prevalence of overweight and
      obesity in China.

PMID- 17228027
TI  - Internalization of weight bias: Implications for binge eating and emotional well
      being.
AB  - OBJECTIVE: This study examined the relationship between internalization of
      negative weight-based stereotypes and indices of eating behaviors and emotional
      well-being in a sample of overweight and obese women. RESEARCH METHOD AND
      PROCEDURES: The sample was comprised of 1013 women who belonged to a national,
      non-profit weight loss organization. Participants completed an on-line battery of
      self-report questionnaires measuring frequency of weight stigmatization and
      coping responses to deal with bias and symptoms of depression and self-esteem,
      attitudes about weight and obesity, and binge eating behaviors. In addition,
      participants were asked to list the most common weight-based stereotypes and
      whether they believed them to be true or false. RESULTS: Participants who
      believed that weight-based stereotypes were true reported more frequent binge
      eating and refusal to diet in response to stigma experiences compared with those
      who reported stereotypes to be false. The degree to which participants believed
      stereotypes to be true or false was not related to types or amount of stigma
      experiences reported, self-esteem, depression, or attitudes toward obese persons.
      In addition, engaging in weight loss strategies as a response to bias was not
      predicted by stereotype beliefs or by actual stigma experiences, regardless of
      the amount or types of stigma reported. DISCUSSION: These findings suggest that
      obese individuals who internalize negative weight-based stereotypes may be
      particularly vulnerable to the negative impact of stigma on eating behaviors and
      also challenge the notion that stigma may motivate obese individuals to engage in
      efforts to lose weight. This study highlights a new area of research that
      warrants attention to better understand weight stigma and its potential
      consequences for health.

PMID- 17228028
TI  - Polyunsaturated fatty acid pattern in liver and erythrocyte phospholipids from
      obese patients.
AB  - OBJECTIVE: Our aim was to study the fatty acid (FA) composition of liver
      phospholipids and its relation to that in erythrocyte membranes from patients
      with obese nonalcoholic fatty liver disease (NAFLD), as an indication of lipid
      metabolism alterations leading to steatosis. RESEARCH METHODS AND PROCEDURES:
      Eight control subjects who underwent antireflux surgery and 12 obese patients
      with NAFLD who underwent subtotal gastrectomy with a gastro-jejunal anastomosis
      in Roux-en-Y were studied. The oxidative stress status of patients was assessed
      by serum F2-isoprostanes levels (gas chromatography/negative ion chemical
      ionization tandem mass spectrometry). Analysis of FA composition of liver and
      erythrocyte phospholipids was carried out by gas-liquid chromatography. RESULTS:
      Patients with NAFLD showed serum F2-isoprostanes levels 84% higher than controls.
      Compared with controls, liver phospholipids from obese patients exhibited
      significantly 1) lower levels of 20:4n-6, 22:5n-3, 22:6n-3 [docosahexaenoic acid
      (DHA)], total long-chain polyunsaturated FA (LCPUFA), and total n-3 LCPUFA, 2)
      higher 22:5n-6 [docosapentaenoic acid (DPAn-6)] levels and n-6/n-3 LCPUFA ratios,
      and 3) comparable levels of n-6 LCPUFA. Levels of DHA and DPAn-6 in liver were
      positively correlated with those in erythrocytes (r = 0.77 and r = 0.90,
      respectively; p < 0.0001), whereas DHA and DPAn-6 showed a negative association
      in both tissues (r = -0.79, p < 0.0001 and r = -0.58, p < 0.01, respectively),
      associated with lower DHA/DPAn-6 ratios. DISCUSSION: Obese patients with NAFLD
      showed marked alterations in the polyunsaturated fatty acid pattern of the liver.
      These changes are significantly correlated with those found in erythrocytes, thus
      suggesting that erythrocyte FA composition could be a reliable indicator of
      derangements in liver lipid metabolism in obese patients.

PMID- 17228029
TI  - Galectin-3 stimulates preadipocyte proliferation and is up-regulated in growing
      adipose tissue.
AB  - OBJECTIVE: Some cytokines and mediators of inflammation can alter adiposity
      through their effects on adipocyte number. To probe the molecular basis of
      obesity, this study determined whether galectin-3 was present in adipose tissue
      and investigated its effects on fat cell number. RESEARCH METHODS AND PROCEDURES:
      In the first study, obesity-prone C57BL/6J mice were fed with high-fat (58%)
      diet. Epididymal fat pads were collected at Day 0, Day 60, and Day 120 after the
      start of high-fat feeding. RESULTS: Levels of adipocyte galectin-3 protein,
      determined using Western blot analysis, increased as the mice became obese.
      Galectin-3 mRNA and protein were then detected in human adipose tissue, primarily
      in the preadipocyte fraction. It was found that recombinant human galectin-3
      stimulated proliferation of primary cultured preadipocytes as well as DNA
      synthesis through lectin-carbohydrate interaction. DISCUSSION: Galectin-3, which
      has been known to play a versatile role especially in immune cells, might play a
      role also in adipose tissue and be associated with the pathophysiology of
      obesity.

PMID- 17228030
TI  - Expression and localization of melanocortin-1 receptor in human adipose tissues
      of severely obese patients.
AB  - OBJECTIVE: The melanocortin system is a key regulator in the hypothalamus of
      energy intake and expenditure. It is frequently linked with obesity and
      apparently modulates sympathetic outflow to white adipose tissues. The role of
      the melanocortins within adipose tissues, however, is not entirely clear. This
      study was aimed at determining the quantitative expression of the five
      melanocortin receptors (MC1-R to MC5-R) in subcutaneous and omental fat of obese
      patients and non-obese subjects. RESEARCH METHODS AND PROCEDURES: Expression of
      MC1-R to MC5-R, proopiomelanocortin, agouti signaling protein, leptin, leptin
      receptor, and uncoupling protein-1 was investigated in human fat samples by
      quantitative reverse transcription-polymerase chain reaction. MC1-R expression
      was also studied in preadipocytes, adipocytes, and monocytic THP-1 cells and by
      immunohistochemical localization in adipose tissues. RESULTS: Notable expression
      was found for MC1-R, whereas no mRNA for MC2-R and MC3-R was detected; MC4-R and
      MC5-R mRNA was occasionally detectable but at very low levels. MC1-R mRNA in
      subcutaneous fat was increased in obese patients as compared with controls;
      omental fat of both groups had slightly higher MC1-R expression than subcutaneous
      fat and did not differ between patient groups. Immunohistochemical analysis of
      the MC1-R in adipose tissue sections showed that MC1-R expression was higher in
      macrophages but also present in adipocytes. DISCUSSION: The expression of MC1-R
      and the lack of MC2-R in human adipose tissues indicate that the melanocortins
      may regulate cell proliferation and/or inflammatory signals rather than
      lipolysis. Also, the increased expression of MC1-R in subcutaneous fat of obese
      subjects may reflect one aspect of the pathophysiology of obesity.

PMID- 17228031
TI  - Chronological approach of diet-induced alterations in muscle mitochondrial
      functions in rats.
AB  - OBJECTIVE: Mitochondrial dysfunction might predispose individuals to develop
      insulin resistance. Our objective was to determine whether mitochondrial
      dysfunction or insulin resistance was the primary event during high-fat (HF)
      diet. RESEARCH METHODS AND PROCEDURES: Rats were fed an HF diet for 0, 3, 6, 9,
      14, 20, or 40 days and compared with control. Soleus and tibialis muscle
      mitochondrial activity were assessed using permeabilized fiber technique. Insulin
      [area under the curve for insulin (AUC(I))] and glucose [area under the curve for
      glucose (AUC(G))] responses to intraperitoneal glucose tolerance test as well as
      fasting plasma non-esterified fatty acids (NEFAs), triglyceride, and glycerol
      concentrations were determined. RESULTS: AUC(I) and AUC(G) were altered from Day
      6 (p < 0.01 vs. Day 0). In soleus, oxidative phosphorylation (OXPHOS) activity
      was transiently enhanced by 26% after 14 days of HF diet (p < 0.05 vs. Day 0)
      conjointly with 62% increase in NEFA concentration (p < 0.05 vs. Day 0). This was
      associated with normalized AUC(G) at Day 14 and with a decline of plasma NEFA
      concentration together with stabilization of intra-abdominal adiposity at Day 20.
      Prolongation of HF diet again caused an increase in plasma NEFA concentration,
      intra-abdominal adiposity, AUC(I), and AUC(G). At Day 40, significant decrease in
      OXPHOS activity was observed in soleus. DISCUSSION: Mitochondria first adapt to
      overfeeding in oxidative muscle limiting excess fat deposition. This potentially
      contributes to maintain glucose homeostasis. Persistent overfeeding causes
      insulin resistance and results in a slow decline in oxidative muscle OXPHOS
      activity. This shows that the involvement of mitochondria in the predisposition
      to insulin resistance is mainly due to an inability to face prolonged excess fat
      delivery.

PMID- 17228032
TI  - Down-regulation of microsomal prostaglandin E2 synthase-1 in adipose tissue by
      high-fat feeding.
AB  - OBJECTIVE: Prostaglandin (PG)E2 is a lipid mediator implicated in inflammatory
      diseases and in the regulation of lipolysis and adipocyte differentiation. This
      work was, thus, undertaken to study the regulation of the various PGE2 synthases
      (PGESs) in obesity. RESEARCH METHODS AND PROCEDURES: C57Bl/6 mice were subjected
      to a high-fat or regular diet for 12 weeks. The levels of PGE2 in white adipose
      tissue (WAT) of lean and obese mice were quantified by liquid chromatography-mass
      spectrometry, and the change in expression of the three major PGES caused by diet
      induced obesity was characterized by Western blotting. Human preadipocytes and
      3T3-L1 cells were used to assess the expression of microsomal prostaglandin E2
      synthase-1 (mPGES-1) during adipogenesis. RESULTS: mPGES-1, mPGES-2, and
      cytosolic PGES proteins were all detected in WAT of lean animals. mPGES-1 was
      expressed at higher levels in WAT than in any other tissues examined and was more
      abundant (3- to 4-fold) in epididymal (visceral) compared with inguinal
      (subcutaneous) WAT. Expression of mPGES-1 was also detected in undifferentiated
      and differentiated 3T3-L1 cells and in human primary subcutaneous preadipocytes
      at all stages of adipogenesis. The mPGES-1 protein was substantially down
      regulated in epididymal and inguinal WAT of obese mice, whereas mPGES-2 and
      cytosolic PGES remained relatively stable. Concordantly, the PGE2 levels in obese
      inguinal WAT were significantly lower than those of lean animals. DISCUSSION:
      These data suggest that mPGES-1 is the major form of PGESs contributing to the
      synthesis of PGE2 in WAT and that its down-regulation might be involved in the
      alterations of lipolysis and adipogenesis associated with obesity.

PMID- 17228033
TI  - Intra-abdominal fat burden discriminated in vivo using proton magnetic resonance
      spectroscopy.
AB  - OBJECTIVE: To assess proton magnetic resonance spectroscopy (1H-MRS) as a means
      to distinguish among mice with disparate intra-abdominal body fat compositions,
      and to measure changes in intra-abdominal fat burden during weight loss and
      regain. RESEARCH METHODS AND PROCEDURES: Intra-abdominal fat burden was analyzed
      as a ratio of integrated areas under the curves of fat to water (1)H-MRS signals
      collected from a region of interest standardized across B6.V-Lep(ob), C57BL/6,
      and A-ZIP/F mice that exhibited various genotypically related body fat
      compositions, ranging from obese (B6.V-Lep(ob)) to minimal body fat (A-ZIP/F). 1H
      MRS analysis of fat burden was compared with intra-abdominal fat volume and with
      a single cross-sectional intra-abdominal fat area calculated from segmented
      magnetic resonance images. Similar measurements were made from obese B6.V-Lep(ob)
      mice before, during, and after they were induced to lose weight by leptin
      administration. RESULTS: Relative amounts of intra-abdominal fat analyzed by 1H
      MRS differed significantly according to body composition and genotype of the
      three strains of mice (p < 0.05). Intra-abdominal fat assessed by 1H-MRS
      correlated with both intra-abdominal fat volume (r = 0.88, p < 0.001) and body
      weight (r = 0.82, p < 0.001) among, but not within, all three genotypes. During
      weight loss and regain, there was a significant overall pattern of changes in
      intra-abdominal fat quantity that occurred, which was reflected by 1H-MRS (p =
      0.006). DISCUSSION: Results support the use of localized 1H-MRS for assessing
      differences in intra-abdominal fat. Refinements in 1H-MRS voxel region of
      interest size and location as well as instrument precision may result in improved
      correlations within certain body compositions.

PMID- 17228034
TI  - Body composition of obese subjects by air displacement plethysmography: The
      influence of hydration.
AB  - OBJECTIVE: We investigated whether air displacement plethysmography (ADP) could
      detect small changes in body composition of obese subjects with alterations in
      hydration. RESEARCH METHODS AND PROCEDURES: Ten obese subjects (mean BMI, 39.3 +/
      2.8 kg/m2) entered the ADP chamber without and with oil (1, 2, or 4 liters),
      water (1, 2, or 4 liters), or mixed (1 liter oil + 1 liter water or 2 liters oil
      + 2 liters water) loads. Real and measured changes in body composition were
      compared by regression analysis and Bland-Altman procedures. RESULTS: The ADP
      measured changes in volume did not differ from the real values and were strongly
      correlated with them (r = 0.98). In all cases, loads of differing composition and
      similar volume led to different values of fat, fat-free mass, and percentage fat.
      Water was detected as increased fat-free mass only with loads of > or =2 liters,
      most of the water being falsely detected as increased fat mass. The observed
      changes were correlated with the real ones for fat mass (r = 0.68; p < 0.0001),
      fat-free mass (r = 0.66; p < 0.0001), and percentage fat (r = 0.61; p < 0.0001),
      but fat mass changes were overestimated by approximately 1 kg, and fat-free mass
      changes were underestimated by approximately 1 kg. This underestimation increased
      with the highest water loads, as shown by the Bland-Altman plot (r = -0.27; p <
      0.05). Percentage fat changes were overestimated by 0.8% (p < 0.001); the
      magnitude of the error was correlated with the weight of the water load (r =
      0.62; p < 0.0001). DISCUSSION: ADP accurately measures changes in body volume,
      discriminating small changes in body composition. It overestimates changes in
      adiposity, as most of the increased hydration is detected as an enlarged fat
      mass.

PMID- 17228035
TI  - Bioelectrical impedance vs. four-compartment model to assess body fat change in
      overweight adults.
AB  - OBJECTIVE: The Tanita TBF-305 body fat analyzer is marketed for home and clinical
      use and is based on the principles of leg-to-leg bioelectrical impedance analysis
      (BIA). Few studies have investigated the ability of leg-to-leg BIA to detect
      change in percentage fat mass (%FM) over time. Our objective was to determine the
      ability of leg-to-leg BIA vs. the four-compartment (4C) model to detect small
      changes in %FM in overweight adults. RESEARCH METHODS AND PROCEDURES: Thirty
      eight overweight adults (BMI, 25.0 to 29.9 kg/m2; age, 18 to 44 years; 31 women)
      participated in a 6-month, randomized, double-blind, placebo-controlled study of
      a nutritional supplement. Body composition was measured at 0 and 6 months using
      the Tanita TBF-305 body fat analyzer [using equations derived by the manufacturer
      (%FM(T-Man)) and by Jebb et al. (%FM(T-Jebb))] and the 4C model (%FM(4C)).
      RESULTS: Subjects in the experimental group lost 0.9%FM(4C) (p = 0.03), a loss
      that did not reach significance using leg-to-leg BIA (0.6%FM(T-Man), p = 0.151;
      0.6%FM(T-Jebb), p = 0.144). We observed large standard deviations (SDs) in the
      mean difference in %FM between the 4C model and the Tanita(Manufacturer) (2.5%)
      and Tanita(Jebb) (2.2%). Ten subjects fell outside +/-1 SD of the mean
      differences at 0 and 6 months; those individuals were younger and shorter than
      those within +/-1 SD. DISCUSSION: Leg-to-leg BIA performed reasonably well in
      predicting decreases in %FM in this group of overweight adults but resulted in
      wide SDs vs. %FM(4C) in individuals. Cross-sectional determinations of %FM of
      overweight individuals using leg-to-leg BIA should be interpreted with caution.

PMID- 17228036
TI  - Pre-meal water consumption reduces meal energy intake in older but not younger
      subjects.
AB  - OBJECTIVE: To determine whether the consumption of water 30 minutes before an ad
      libitum meal reduces meal energy intake in young and older adults. RESEARCH
      METHODS AND PROCEDURES: Healthy, non-obese young (n = 29; age, 21 to 35 years)
      and older (n = 21; age, 60 to 80 years) individuals were provided with an ad
      libitum lunch meal on two occasions. Thirty minutes before the lunch meals,
      subjects were given either a water preload (WP: 375 mL, women; 500 mL, men) or no
      preload (NP). Energy intake at the two lunch meals was measured. Visual analog
      scales were used to assess changes in hunger, fullness, and thirst during the
      meal studies. RESULTS: There was no significant difference in meal energy intake
      between conditions in the young subjects (892 + 51 vs. 913 +/- 54 kcal for NP and
      WP, respectively; p = 0.65). However, meal energy intake after the WP was
      significantly reduced relative to the NP condition in the older subjects (682 +
      53 vs. 624 +/- 56 kcal for NP and WP, respectively; p = 0.02). This effect was
      caused primarily by the reduction in meal energy intake after water consumption
      in older men. Hunger ratings were lower and fullness ratings were higher in older
      compared with younger adults (p < 0.01). Fullness ratings were higher in the WP
      condition compared with the NP condition for all subjects (p = 0.01). No age
      differences in thirst were detected during the test meals. DISCUSSION: Under
      acute test meal conditions, pre-meal water consumption reduces meal energy intake
      in older but not younger adults. Because older adults are at increased risk for
      overweight and obesity, intervention studies are needed to determine whether pre
      meal water consumption is an effective long-term weight management strategy for
      the aging population.

PMID- 17228037
TI  - Association of eating frequency with body fatness in pre- and postmenopausal
      women.
AB  - OBJECTIVE: To examine associations between eating frequency (EF) and body fatness
      in pre- and postmenopausal women, after excluding potential low-energy reporters.
      RESEARCH METHODS AND PROCEDURES: In this cross-sectional study of 220 free-living
      women, 64 pre- and 50 postmenopausal non-low-energy-reporting women were further
      analyzed (age, 24 to 74 years; BMI, 18.5 to 38.6 kg/m2). Anthropometric and body
      composition measurements (DXA) were performed in all study participants. EF,
      energy, and macronutrient intake were assessed by 3-day food record. Physical
      activity level and energy expenditure were assessed by self-reported
      questionnaire. RESULTS: No association between EF and adiposity indices was
      detected in premenopausal women. In contrast, EF was positively correlated with
      percentage body fat in postmenopausal women (r = 0.30, p = 0.03). EF was
      positively correlated with total energy intake in both groups and with total
      energy expenditure in premenopausal women only (r = 0.34, p = 0.02). Multivariate
      analysis revealed that, in postmenopausal women, EF was a significant predictor
      of body fatness (standardized beta = 0.41, p = 0.01). DISCUSSION: Frequent eating
      was not found to be related to adiposity in premenopausal women, but it was
      associated with increased body fat in postmenopausal women. Possible explanations
      could be that the frequent eating is not associated with a physically active
      lifestyle in postmenopausal women or that frequent eating predisposes women after
      menopause to a higher energy intake by increasing food stimuli and rendering it
      more difficult for them to control energy balance.

PMID- 17228038
TI  - Nut consumption and weight gain in a Mediterranean cohort: The SUN study.
AB  - OBJECTIVE: To assess the association, in a Mediterranean population, between nut
      consumption and risk of weight gain (at least 5 kg) or the risk of becoming
      overweight/obese. RESEARCH METHODS AND PROCEDURES: The Seguimiento Universidad de
      Navarra project is a prospective cohort of 8865 adult men and women who completed
      a follow-up questionnaire after a median of 28 months. Dietary habits were
      assessed with a previously validated semiquantitative food-frequency
      questionnaire. RESULTS: Nine hundred thirty-seven participants reported a weight
      gain of > or =5 kg at follow-up. After adjusting for age, sex, smoking, leisure
      time physical activity, and other known risk factors for obesity, participants
      who ate nuts two or more times per week had a significantly lower risk of weight
      gain (odds ratio: 0.69; 95% confidence interval: 0.53 to 0.90, p for trend =
      0.006) than those who never or almost never ate nuts. Participants with little
      nut consumption (never/almost never) gained an average of 424 grams (95%
      confidence interval: 102 to 746) more than frequent nut eaters. Nut consumption
      was not significantly associated with incident overweight/obesity in the cohort.
      DISCUSSION: Frequent nut consumption was associated with a reduced risk of weight
      gain (5 kg or more). These results support the recommendation of nut consumption
      as an important component of a cardioprotective diet and also allay fears of
      possible weight gain.

PMID- 17228040
TI  - Controlled study of critical parent and family factors in the obesigenic
      environment.
AB  - OBJECTIVE: Critical gaps remain in our understanding of the obesigenic family
      environment. This study examines parent and family characteristics among obese
      youth presenting for treatment in a clinic setting. RESEARCH METHODS AND
      PROCEDURES: Families of 78 obese youth (BMI z-score = 2.4; age, 8 to 16 years;
      59% girls; 49% African-American) were compared with 71 non-overweight (BMI z
      score = -0.02) demographically matched comparisons. Parents completed measures
      assessing family demographics, psychological distress (Symptom Checklist 90
      Revised), and family functioning both broadly (Family Environment Scale:
      Conflicted, Support, Control) and at mealtimes (About Your Child's Eating
      Revised: Mealtime Challenges, Positive Mealtime Interaction). Height and weight
      were obtained from all participants. RESULTS: Compared with mothers and fathers
      of non-overweight youth, parents of obese youth had significantly higher BMIs (p
      < 0.001). Mothers of obese youth reported significantly greater psychological
      distress (p < 0.01), higher family conflict (p < 0.05), and more mealtime
      challenges (p < 0.01). Less positive family mealtime interactions were reported
      by both mothers (p < 0.01) and fathers (p < 0.05) of obese youth. These group
      differences did not vary by child sex or race. Logistic regression analyses
      indicated that maternal distress and mealtime challenges discriminated between
      obese and non-overweight youth after controlling for maternal BMI. Family
      conflict was explained, in part, by maternal distress. DISCUSSION: Obese youth
      who present for treatment in a clinic setting are characterized by psychosocial
      factors at the parent and family level that differ from non-overweight youth.
      These data are critical because they identify factors that may be serving as
      barriers to a family's or youth's ability to implement healthy lifestyle
      behaviors but that are potentially modifiable.

PMID- 17228039
TI  - Desaturation of skeletal muscle structural and depot lipids in obese individuals
      during a very-low-calorie diet intervention.
AB  - OBJECTIVE: This study investigated whether a very-lowcalorie dietary intervention
      (VLCD) may influence composition of skeletal muscle cell membrane phospholipid
      and composition and concentration of intramyocellular triglyceride (IMTG) in
      obese subjects. The working hypothesis proposed that a VLCD would decrease
      saturated fatty acids (FAs) and increase long-chain polyunsaturated FAs (LCPUFAs)
      in muscular structural lipids, as such changes have been associated with improved
      insulin sensitivity. RESEARCH METHODS AND PROCEDURES: Skeletal muscle biopsies
      (vastus lateralis) were obtained from 13 obese subjects (nine women) before and
      after 8 weeks on VLCD (approximately 600 to 800 kcal/d). FA composition in muscle
      cell membrane phospholipid and concentration and FA composition of IMTG were
      determined by gas-liquid chromatography. RESULTS: Baseline BMI was 36.0 +/- 3.4
      kg/m2. Weight loss was 9.3 +/- 1.1 kg (8.8 +/- 1.1%; p < 0.0001); loss of adipose
      tissue was 5.9 +/- 0.9 kg (p < 0.0001). Insulin resistance (by homeostasis model
      assessment) decreased (-44 +/- 7%; p < 0.001). Muscle cell membrane phospholipid
      saturated FAs decreased (-3.2 +/- 1.3%; p < 0.05), whereas monounsaturated FAs
      (4.3 +/- 1.7%; p < 0.05), LCPUFAs (11 +/- 6%; p < 0.05), and the ratio of LCPUFAs
      to saturated FAs (12 +/- 5%; p < 0.05) increased. IMTG decreased, but not
      significantly (-5%). IMTG-saturated FAs decreased (-3.3 +/- 1.5%; p < 0.05),
      whereas LCPUFAn-3 (29 +/- 9%; p < 0.01), LCPUFAn-6 (33 +/- 9%; p < 0.01), and the
      ratio of LCPUFAs to saturated FAs (34 +/- 8%; p < 0.001) increased. Plasma total
      cholesterol (-15 +/- 6%; p < 0.05), low-density lipoprotein-cholesterol (-16 +/-
      5%; p < 0.01), high-density lipoprotein-cholesterol (-8 +/- 2%; p < 0.01), and
      plasma triglyceride (-19 +/- 12%; p = 0.10) all decreased during the VLCD.
      DISCUSSION: Desaturation of both muscle cell membrane phospholipid and IMTG was
      significant but modest during a VLCD in obese subjects. Further research must
      delineate whether such changes in skeletal muscle structural and depot lipid
      composition themselves are enough to promote the observed improvements in insulin
      action.

PMID- 17228041
TI  - Associations between multiple measures of parental feeding and children's
      adiposity in United Kingdom preschoolers.
AB  - OBJECTIVE: Research into the association between parental control over feeding
      and children's adiposity has produced inconclusive results. Some studies have
      found parental control to be associated with unhealthy food choices and
      disordered intake regulation, whereas others have found favorable or null
      associations between control and adiposity. This study hypothesized that
      variability in measures of parental feeding could contribute to these
      discrepancies. Scales from a range of existing parental feeding questionnaires
      were used together, in the same large sample of children, to examine associations
      with adiposity. RESEARCH METHODS AND PROCEDURES: Associations between scores on
      scales from three published parental feeding questionnaires [Child Feeding
      Questionnaire (CFQ); Preschooler Feeding Questionnaire (PFQ); and Parental
      Feeding Style Questionnaire (PFSQ)] and children's BMI z-scores, calculated from
      measured heights and weights, were examined in a socioeconomically diverse sample
      of 439 parents and their 3- to 5-year-old children. RESULTS: Higher scores on CFQ
      Pressure to Eat and PFQ Pushing the Child to Eat More were significantly
      associated with lower BMI z-score, while PFSQ Prompting to Eat, CFQ Restriction,
      PFSQ Instrumental Feeding, and PFSQ Emotional Feeding were unassociated with BMI
      z-score. DISCUSSION: These results suggest that parents of leaner children are
      more likely to encourage their children to eat. Other feeding strategies seemed
      to have negligible relationships with children's BMI z-scores at this stage.
      Longitudinal and genetically informed designs are needed to clarify the causal
      pathways between parental feeding and children's adiposity.

PMID- 17228042
TI  - Psychosocial and physical impairment in overweight adolescents at high risk for
      eating disorders.
AB  - OBJECTIVE: Many overweight adolescents display elevated risk for the development
      of eating disorders, as seen in higher rates of weight/shape concerns and
      disordered eating behaviors, but the extent of impairment in this subset of high
      risk adolescents has not been explored. RESEARCH METHODS AND PROCEDURES: Eighty
      one overweight adolescents (63% girls) presenting for an Internet-based weight
      loss program were assessed at baseline using the Eating Disorder Examination
      Questionnaire, the Depression, Anxiety, and Stress Scale, and the Pediatric
      Quality of Life questionnaire. Adolescents who earned elevated scores on both the
      Weight Concern and Shape Concern subscales of the Eating Disorder Examination
      Questionnaire were considered at high risk for the development of eating
      disorders (56.8%). RESULTS: Comparisons of high- and normal-risk groups revealed
      that high-risk adolescents reported higher levels of depression [F(3,76) = 5.75,
      p = 0.019], anxiety [F(3,76) = 5.67, p = 0.020], and stress [F(3,75) = 8.50, p =
      0.005], and greater impairments in physical health [F(3,77) = 10.7, p = 0.002],
      emotional functioning [F(3,77) = 5.3, p = 0.024], and social functioning [F(3,77)
      = 10.0, p = 0.002]. There were no differences in school functioning [F(3,77) =
      1.5, p = 0.219]. Among the high-risk adolescents, over half (52.2%) reported
      binge eating at least once in the past month. DISCUSSION: Results suggest that
      overweight adolescents at high risk for the development of eating disorders also
      experience elevated levels of negative affect, impairment in health-related
      quality of life, and eating disturbances, although prospective data are needed to
      determine the directionality between eating disorder pathology and general
      psychopathology. Further research is warranted to evaluate whether behavioral
      weight loss interventions should be enhanced for this high-risk subset.

PMID- 17228043
TI  - Weight loss on the web: A pilot study comparing a structured behavioral
      intervention to a commercial program.
AB  - OBJECTIVE: Internet weight loss programs have become widely available as
      alternatives to standard treatment, but few data are available on their efficacy.
      This study aimed to investigate the effectiveness of a structured behavioral
      weight loss website (VTrim) vs. a commercial weight loss website (eDiets.com).
      RESEARCH METHODS AND PROCEDURES: A randomized, controlled trial was conducted
      from February 2003 to March 2005, in 124 overweight and obese subjects ages 18
      years and older with a BMI of 25 to 39.9 kg/m2 (mean age, 47 +/- 9 years; BMI, 32
      +/- 3 kg/m2; 20% men). Analyses were performed for the 88 subjects who had
      complete follow-up data. Participants were randomly assigned to 12-month VTrim (n
      = 62) or eDiets.com (n = 62) intervention. VTrim participants had access to a
      therapist-led structured behavioral weight loss program delivered on-line.
      eDiets.com subjects had access to a self-help commercial on-line weight loss
      program. Body weight, social support, and use of website components were measured
      at 0, 6, and 12 months. RESULTS: Repeated-measures analyses showed that the VTrim
      group lost significantly more weight than the eDiets.com group at 6 months (8.3
      +/- 7.9 kg vs. 4.1 +/- 6.2 kg; p = 0.004) and maintained a greater loss at 12
      months (7.8 +/- 7.5 kg vs. 3.4 +/- 5.8 kg; p = 0.002). More participants in the
      VTrim group maintained a 5% weight loss goal (65% vs. 37.5%; p = 0.01) at 12
      months. DISCUSSION: An on-line, therapist-led structured behavioral weight loss
      website produced greater weight loss than a self-help commercial website. Because
      commercial sites have great potential public health impact, future research
      should investigate the feasibility of incorporating a more structured behavioral
      program into a commercial application.

PMID- 17228044
TI  - DXA measurements confirm that parental perceptions of elevated adiposity in young
      children are poor.
AB  - OBJECTIVE: To compare parental assessments of child body weight status with BMI
      measurements and determine whether children who are incorrectly classified differ
      in body composition from those whose parents correctly rate child weight. Also to
      ascertain whether children of obese parents differ from those of non-obese
      parents in actual or perceived body weight. RESEARCH METHODS AND PROCEDURES:
      Weights, heights, BMI, and waist girths of New Zealand children ages 3 to 8 years
      were determined. Fat mass, fat percentage, and lean mass were measured by DXA (n
      = 96). Parents classified child weight status as underweight, normal-weight,
      slightly overweight, or overweight. Centers for Disease Control and Prevention
      2000 percentiles of BMI were used. RESULTS: Parents underestimated child weight
      status. Despite having 83% more fat mass than children with BMI values below the
      85th percentile, only 7 of 31 children with BMI values at or above the 85th
      percentile were rated as slightly overweight or overweight. In the whole sample,
      participants whose weight status was underestimated by parents (40 of the 96
      children) had l9% less fat mass but similar lean mass as children whose weight
      status was correctly classified. However, children of obese and non-obese parents
      did not differ in body composition or anthropometry, and obese parents did not
      underestimate child weight more than non-obese parents. DISCUSSION: Because
      parents underestimate child weight, but BMI values at or above the 85th
      percentile identify high body fat well, advising parents of the BMI status of
      their children should improve strategies to prevent excessive fat gain in young
      children.

PMID- 17228045
TI  - Lifecourse socioeconomic position and weight change among blacks: The Pitt County
      study.
AB  - OBJECTIVE: The elevated prevalence of obesity among U.S. blacks has been
      attributed to low socioeconomic position (SEP), despite inconsistent empirical
      findings. It is unclear whether low SEP at various lifecourse stages
      differentially influences adulthood BMI and BMI change. RESEARCH METHODS AND
      PROCEDURES: Among 1167 black adults in the Pitt County Study, we examined
      independent cross-sectional and longitudinal associations between SEP, measured
      in childhood and adulthood, and BMI and 13-year BMI change. Low vs. high
      childhood SEP was measured by parental occupation and childhood household
      deprivation; low vs. high adulthood SEP was assessed by employment status,
      education, and occupation. Using childhood and adulthood SEP, four lifecourse SEP
      categories were created: low-low, low-high, high-low, high-high. RESULTS: We
      found no consistent associations between SEP and BMI or BMI change among men.
      Among women, we observed the expected inverse association between SEP and BMI at
      baseline. In multivariable-adjusted analyses, socioeconomically advantaged women
      demonstrated larger 13-year increases in BMI: skilled vs. unskilled parental
      occupation (6.1 vs. 4.8 kg/m2, p = 0.04); college-educated vs. < high school (6.2
      vs. 4.5 kg/m2, p = 0.04); white-collar vs. blue-collar job (5.8 vs. 4.8 kg/m2, p
      = 0.05); and high-high vs. low-low lifecourse SEP (6.5 vs. 4.6 kg/m2, p = 0.02).
      DISCUSSION: For women in this black cohort, lower SEP predicted earlier onset of
      obesity; however, low SEP was less predictive of BMI increases over time. Our
      findings demonstrate complex patterns of association between SEP and BMI change
      among black women.

PMID- 17228046
TI  - The effects of a low-carbohydrate ketogenic diet and a low-fat diet on mood,
      hunger, and other self-reported symptoms.
AB  - OBJECTIVE: To investigate the effects of weight loss diets on mood, food
      cravings, and other self-reported symptoms. RESEARCH METHODS AND PROCEDURES: Mood
      and other symptoms were evaluated by participant self-report using the Atkins
      Health Indicator Test (AHIT) in individuals undergoing weight loss following
      either a low-carbohydrate, ketogenic diet (LCKD) or a low-fat diet (LFD).
      Participants were 119 overweight community volunteers randomized to an LCKD or an
      LFD. An additional 51 participants who had completed an earlier trial contributed
      data for the psychometric analyses but were not included in the prospective
      analyses. Self-reported symptom levels on seven scales factor-analytically
      derived from the AHIT (negative affect, fatigue, somatic symptoms, physical
      effects of hunger, insomnia, hunger, and stomach problems) were acquired during
      12 visits. RESULTS: After adjusting for the change in BMI over the course of the
      trial, participants experienced significant improvements in most symptoms
      regardless of diet. Diet group x visit interactions were observed for negative
      affect [F(9,803) = 2.30, p = 0.015] and hunger [F(9,803) = 3.62, p < 0.0002].
      Examination of means indicated that the LCKD group reported less negative affect
      and hunger, compared with the LFD group. DISCUSSION: Regardless of diet,
      participants experienced significant improvement in a broad range of symptoms.
      Symptoms of negative affect and hunger improved to a greater degree in patients
      following an LCKD compared with those following an LFD. Whether these symptom
      changes explain the greater short-term weight loss generally experienced by LCKD
      followers deserves further research.

PMID- 17228047
TI  - Comparison of self-reported and measured BMI as correlates of disease markers in
      US adults.
AB  - OBJECTIVE: The purpose of this study is to evaluate the validity of BMI based on
      self-reported data by comparison with technician-measured BMI and biomarkers of
      adiposity. RESEARCH METHODS AND PROCEDURES: We analyzed data from 10,639 National
      Health and Nutrition Education Study III participants > or =20 years of age to
      compare BMI calculated from self-reported weight and height with BMI from
      technician-measured values and body fatness estimated from bioelectrical
      impedance analysis in relation to systolic blood pressure, fasting blood levels
      of glucose, high-density lipoprotein-cholesterol, triglycerides, C-reactive
      protein, and leptin. RESULTS: BMI based on self-reported data (25.07 kg/m2) was
      lower than BMI based on technician measurements (25.52 kg/m2) because of
      underreporting weight (-0.56 kg; 95% confidence interval, -0.71, -0.41) and
      overreporting height (0.76 cm; 95% confidence interval, 0.64, 0.88). However, the
      correlations between self-reported and measured BMI values were very high (0.95
      for whites, 0.93 for blacks, and 0.90 for Mexican Americans). In terms of
      biomarkers, self-reported and measured BMI values were equally correlated with
      fasting blood glucose (r = 0.43), high-density lipoprotein-cholesterol (r = 
      0.53), and systolic blood pressure (r = 0.54). Similar correlations were observed
      for both measures of BMI with plasma concentrations of triglycerides and leptin.
      These correlations did not differ appreciably by age, sex, ethnicity, or obesity
      status. Correlations for percentage body fat estimated through bioelectrical
      impedance analysis with these biomarkers were similar to those for BMI.
      DISCUSSION: The accuracy of self-reported BMI is sufficient for epidemiological
      studies using disease biomarkers, although inappropriate for precise measures of
      obesity prevalence.

PMID- 17228048
TI  - The validity of obesity based on self-reported weight and height: Implications
      for population studies.
AB  - OBJECTIVE: To validate self-reported information on weight and height in an adult
      population and to find a useful algorithm to assess the prevalence of obesity
      based on self-reported information. RESEARCH METHODS AND PROCEDURES: This was a
      cross-sectional survey consisting of 1703 participants (860 men and 843 women, 30
      to 75 years old) conducted in the community of Vara, Sweden, from 2001 to 2003.
      Self-reported weight, height, and corresponding BMI were compared with measured
      data. Obesity was defined as measured BMI > or = 30 kg/m2. Information on
      education, self-rated health, smoking habits, and physical activity during
      leisure time was collected by a self-administered questionnaire. RESULTS: Mean
      differences between measured and self-reported weight were 1.6 kg (95% confidence
      interval, 1.4; 1.8) in men and 1.8 kg (1.6; 2.0) in women (measured higher),
      whereas corresponding differences in height were -0.3 cm (-0.5; -0.2) in men and 
      0.4 cm (-0.5; -0.2) in women (measured lower). Age and body size were important
      factors for misreporting height, weight, and BMI in both men and women. Obesity
      (measured) was found in 156 men (19%) and 184 women (25%) and with self-reported
      data in 114 men (14%) and 153 women (20%). For self-reported data, the
      sensitivity of obesity was 70% in men and 82% in women, and when adjusted for
      corrected self-reported data and age, it increased to 81% and 90%, whereas the
      specificity decreased from 99% in both sexes to 97% in men and 98% in women.
      DISCUSSION: The prevalence of obesity based on self-reported BMI can be estimated
      more accurately when using an algorithm adjusted for variables that are
      predictive for misreporting.

PMID- 17228049
TI  - BMI and retinal vascular caliber in children.
AB  - OBJECTIVE: In adult populations, changes in retinal vascular caliber have been
      linked with obesity and metabolic syndrome. We examined the association of BMI
      and weight with retinal vascular caliber in children. RESEARCH METHODS AND
      PROCEDURES: This was a school-based, cross-sectional study of 768 children, 7 to
      9 years old, randomly sampled from the Singapore Cohort Study of the Risk Factors
      for Myopia. Participants had digital retinal photographs. Retinal vascular
      caliber was measured using a computer-based program and combined to provide
      average calibers of arterioles and venules in that eye. Weight and height were
      measured using standardized protocol. These data were used to calculate BMI.
      RESULTS: In this population, the mean retinal arteriolar and venular calibers
      were 156.40 microm [95% confidence interval (CI), 155.44 to 157.36] and 225.43
      microm (95% CI, 224.10 to 226.74) respectively. After controlling for age,
      gender, race, parental monthly income, axial length, birth weight, and birth
      length, each 3.1 kg/m2 (standard deviation) increase in BMI was associated with a
      2.55-microm (95% CI, 1.21 to 3.89; p < 0.001) larger retinal venular caliber. In
      multivariable analysis, greater weight was also significantly associated with
      larger retinal venular caliber. BMI and weight were not associated with retinal
      arteriolar caliber. Height was not significantly associated with retinal
      arteriolar or venular caliber. DISCUSSION: Greater BMI and weight are associated
      with larger retinal venular caliber in healthy children.

PMID- 17228050
TI  - Increasing trends in waist circumference and abdominal obesity among US adults.
AB  - OBJECTIVE: Some studies have shown that abdominal obesity may be a better
      predictor than overall obesity for disease risks and all-cause mortality. This
      study sought to examine the recent trends in waist circumference (WC) among
      adults in the United States. RESEARCH METHODS AND PROCEDURES: Data from the
      National Health and Nutrition Examination Survey during 1988-1994, 1999-2000,
      2001-2002, and 2003-2004 were analyzed to estimate the trends in the mean WC and
      the prevalence of abdominal obesity. Pooled t tests were used to test the
      differences in estimates between two time periods. RESULTS: Between the periods
      of 1988-1994 and 2003-2004, the age-adjusted mean WC increased from 96.0 cm to
      100.4 cm among men (p < 0.001) and from 89.0 cm to 94.0 cm among women (p <
      0.001); the age-adjusted prevalence of abdominal obesity increased from 29.5% to
      42.4% among men (p < 0.001) and from 47.0% to 61.3% among women (p < 0.001).
      Between the periods of 1999-2000 and 2003-2004, a significant increase occurred
      in mean WC only among men (from 99.0 cm to 100.4 cm; p = 0.03) and in the
      prevalence of abdominal obesity among both men (from 37.0% to 42.2%; p = 0.03)
      and women (from 55.3% to 61.3%; p = 0.04). People with a BMI of 25 to 29 kg/m2
      had a greater relative increase in abdominal obesity. DISCUSSION: The mean WC and
      the prevalence of abdominal obesity among U.S. adults have increased continuously
      during the past 15 years. Over one-half of U.S. adults had abdominal obesity in
      the period of 2003-2004.

PMID- 17228051
TI  - Recognition of childhood overweight during health supervision visits: Does BMI
      help pediatricians?
AB  - OBJECTIVE: To assess, in diverse pediatric practices, the frequency of
      overweight/obesity (OW/OB) identification during health supervision visits and
      its association with BMI curve use. RESEARCH METHODS AND PROCEDURES:
      Pediatricians in public and private practice in St. Louis, MO, participated in a
      study of the care of chronic conditions during health supervision visits.
      Requested information from 30 visits per pediatrician of children 6 to 17 years
      of age included the visit note, the growth chart, and a one-page questionnaire
      about patient demographics and visit content. Pediatricians indicated the
      presence and discussion of common chronic conditions, including OW/OB.
      Identification was compared with patient BMI category, and associations between
      identification and patient and visit characteristics, including BMI curve use,
      were examined. RESULTS: Twenty-one (40%) of contacted pediatricians returned
      information from 557 visits. Pediatricians identified OW/OB in 27% of children
      with a BMI at the 85th to 94th percentile and 86% of children with a BMI at or
      above the 95th percentile. Identification was higher in adolescents but was not
      associated with patient sex or race, practice setting, insurance type, or visit
      length. Only 41% of growth charts were current, and 6.1% had BMI plotted. BMI
      plotting was associated with OW/OB identification when the BMI was at the 85th to
      94th percentile but not when the BMI was at or above the 95th percentile. After
      controlling for BMI percentile, OW/OB identification was significantly associated
      with diet counseling (odds ratio, 7.46; 95% confidence interval, 3.42 to 16.24)
      and exercise counseling (odds ratio, 5.57; 95% confidence interval, 2.61 to
      11.90). DISCUSSION: Despite low BMI curve use, pediatricians recognized most
      overweight/obese children with a BMI at or above the 95th percentile. BMI
      plotting may increase recognition in mildly overweight children.

PMID- 17228052
TI  - Waist circumference as a predictor of disability among older adults.
AB  - OBJECTIVE: Few studies have addressed the association between abdominal obesity,
      as measured by waist circumference (WC), and disability in the elderly. Moreover,
      those studies were cross-sectional and yielded inconsistent results. The
      objective of this study was to examine longitudinally the association between WC
      and self-reported disability among older adults. RESEARCH METHODS AND PROCEDURES:
      A prospective cohort study was conducted from 2001 to 2003 in 3235 persons (1411
      men and 1824 women) representative of the non-institutionalized Spanish
      population ages 60 years and older. Baseline information was collected by home
      based personal interviews and measurement of WC, weight, and height. Two years
      later, information on disability was obtained by telephone interview. The
      association of interest was summarized with odds ratios obtained by logistic
      regression. RESULTS: Among persons reporting no disability at baseline, WC
      predicted disability 2 years later. After adjustment for age, education, tobacco
      use, alcohol consumption, and physical activity, men in the highest WC quintile
      had 2.17 (95% confidence interval, 1.15 to 4.09) times more risk of mobility
      disability and 4.77 (95% confidence interval, 2.50 to 9.13) times more risk of
      agility disability than those in the lowest quintile. Additional adjustment for
      BMI, chronic diseases, and cognitive function led to only a slight reduction in
      this association. Results were similar for women. No statistically significant
      association was observed between WC and restriction of daily activities,
      limitation in instrumental activities of daily living, and limitation in bathing
      or dressing, in either men or women. DISCUSSION: WC predicts mobility and agility
      disability in old age. Avoidance of the highest values of WC might decrease the
      risk of disability in older adults.

PMID- 17228053
TI  - Burden of infection and fat mass in healthy middle-aged men.
AB  - OBJECTIVE: Our aim was to study the effect of exposure to four infections on fat
      mass. RESEARCH METHODS AND PROCEDURES: This was a cross-sectional study of
      healthy middle-aged men from the general population (n = 74). 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 (ELISAs). A total
      pathogen burden score based on these seropositivities [Quantitative
      Seropositivity Index (QSI)] was constructed. Fat mass was measured by
      bioelectrical impedance. RESULTS: We observed significant relationships between
      the HSV-1 titer and fat mass and percentage fat mass. The associations were
      stronger when considering the infection burden. The QSI was significantly
      associated with fat mass (r = 0.30, p = 0.009) and percentage fat mass (r = 0.27,
      p = 0.01). Those subjects in the highest tertile of fat mass showed significantly
      higher QSI (259.5 +/- 74.1 vs. 206.9 +/- 78.2, p = 0.007). In subjects that were
      seropositive for Enteroviruses, the relationship between the QSI and fat mass was
      strengthened (r = 0.51, p = 0.02). In a multivariate regression analysis, the
      QSI, independently of age and C-reactive protein, contributed to 9% of fat mass
      variance. DISCUSSION: Pathogen burden showed an association with fat mass.
      Subjects with increased fat mass could be more susceptible to developing multiple
      infections resulting in a chronic low-grade inflammation. We can not exclude the
      possibility that exposure to multiple infections leads to increased fat mass.

PMID- 17228054
TI  - Short sleep duration is associated with reduced leptin levels and increased
      adiposity: Results from the Quebec family study.
AB  - OBJECTIVE: To explore cross-sectional associations between short sleep duration
      and variations in body fat indices and leptin levels during adulthood in a sample
      of men and women involved in the Quebec Family Study. RESEARCH METHODS AND
      PROCEDURES: Anthropometric measurements, plasma lipid-lipoprotein profile, plasma
      leptin concentrations, and total sleep duration were determined in a sample of
      323 men and 417 women ages 21 to 64 years. RESULTS: When compared with adults
      reporting 7 to 8 hours of sleep per day, the adjusted odds ratio for
      overweight/obesity was 1.38 (95% confidence interval, 0.89 to 2.10) for those
      with 9 to 10 hours of sleep and 1.69 (95% confidence interval, 1.15 to 2.39) for
      those with 5 to 6 hours of sleep, after adjustment for age, sex, and physical
      activity level. In each sex, we observed lower adiposity indices in the 7- to 8
      hour sleeping group than in the 5- to 6-hour sleeping group. However, all of
      these significant differences disappeared after statistical adjustment for plasma
      leptin levels. Finally, the well-documented regression of plasma leptin levels
      over body fat mass was used to predict leptin levels of short-duration sleepers
      (5 and 6 hours of sleep), which were then compared with their measured values. As
      expected, the measured leptin values were significantly lower than predicted
      values. DISCUSSION: There may be optimal sleeping hours at which body weight
      regulation is facilitated. Indeed, short sleep duration predicts an increased
      risk of being overweight/obese in adults and is related to a reduced circulating
      leptin level relative to what is predicted by fat mass. Because sleep duration is
      a potentially modifiable risk factor, these findings might have important
      clinical implications for the prevention and treatment of obesity.

PMID- 17228055
TI  - The impact of central obesity as a prerequisite for the diagnosis of metabolic
      syndrome.
AB  - OBJECTIVE: To compare the prevalence of metabolic syndrome (MS) defined according
      to the American Heart Association (AHA)/National Heart Lung and Blood Institute
      (NHLBI) and the International Diabetes Federation (IDF) and to determine the
      effect of the presence of central obesity on the phenotype (insulin resistance
      and other cardiovascular risk factors) associated with MS. RESEARCH METHODS AND
      PROCEDURES: We studied 4723 Chinese, Malays, and Asian Indians living in
      Singapore. Each individual was categorized according to the five criteria for MS
      as defined by the AHA/NHLBI and the IDF. The population was categorized according
      to the presence of three or more criteria and then further subcategorized
      according to the presence or absence of central obesity. Characteristics of each
      group were compared using ANOVA and the chi2 test. RESULTS: MS was present in
      20.2% (IDF) and 26.9% (AHA/NHLBI) of the population. Of the population, 6.7%
      exhibited three or more features of MS without central obesity. Use of the IDF
      definition, which requires central obesity, is associated with greater insulin
      resistance but similar levels of other cardiovascular disease risk factors than
      the use of the AHA/NHLBI definition, which does not require central obesity.
      DISCUSSION: In this Southeast Asian population, the IDF and the AHA/NHLBI
      definitions of MS identify different segments of the MS population. The IDF
      definition may be more appropriate for the identification of those with insulin
      resistance and increased risk of type 2 diabetes. In contrast, the AHA/NHLBI
      definition may better identify those at increased risk of cardiovascular disease.

PMID- 17228056
TI  - Targeted protein degradation by Salmonella under phagosome-mimicking culture
      conditions investigated using comparative peptidomics.
AB  - The pathogen Salmonella enterica is known to cause both food poisoning and
      typhoid fever. Because of the emergence of antibiotic-resistant isolates and the
      threat of bioterrorism (e.g. contamination of the food supply), there is a
      growing need to study this bacterium. In this investigation, comparative
      peptidomics was used to study S. enterica serovar Typhimurium cultured in either
      a rich medium or in an acidic, low magnesium, and minimal nutrient medium
      designed to roughly mimic the macrophage phagosomal environment (within which
      Salmonella are known to survive). Native peptides from cleared cell lysates were
      enriched by using isopropanol extraction and analyzed by using both LC-MS/MS and
      LC-FTICR-MS. We identified and quantified 5,163 peptides originating from 682
      proteins, and the data clearly indicated that compared with Salmonella cultured
      in the rich medium, cells cultured in the phagosome-mimicking medium had
      dramatically higher abundances of a wide variety of protein degradation products,
      especially from ribosomal proteins. Salmonella from the same cultures were also
      analyzed using traditional, bottom-up proteomic methods, and when the peptidomics
      and proteomics data were analyzed together, two clusters of proteins targeted for
      proteolysis were tentatively identified. Possible roles of targeted proteolysis
      by phagocytosed Salmonella are discussed.

PMID- 17228057
TI  - Proline-rich regions in transcriptional complexes: heading in many directions.
AB  - Although many protein complexes are now known, the precise details of how each
      component operates are rarely understood. Through a combination of bioinformatics
      and analysis of gene-trapped mouse clones, Enkhmandakh et al. were able to deduce
      the modular function for a part of Ssdp1, a crucial component of the Ldb1
      transcriptional complex, which plays a central role in mammalian head
      development. A proline-rich module from Ssdp1 is likely responsible for
      transactivation, and this region is curiously mobile, occurring in different
      proteins in different species. The results underscore the importance of protein
      modularity in complex organization, as well as the role of irregular or
      disordered parts of proteins in crucial biological processes.

PMID- 17228059
TI  - Quality of life of older adults in Canada and Brazil.
AB  - In this study, we examined the factors contributing to quality of life (QOL) of
      older adults in regions of Canada and Brazil. The WHOQOL-BREF and a demographic
      data sheet were administered to random samples of 202 older adults from Canada
      and 288 from Brazil. Ratings on overall QOL and on the physical, psychological,
      and environmental domains were higher in the Canadian sample. Social domain
      scores were not significantly different. The authors found the same pattern of
      factors (health satisfaction, enough money, meaning in life, and opportunities
      for leisure activities) contributed to the variance of QOL in both countries,
      except for physical environment, which was significant in Brazil and not in
      Canada. Health satisfaction was the strongest contributor to QOL in both samples,
      and satisfaction with personal relationships was not significant in either
      country.

PMID- 17228060
TI  - Adherence to a behavioral program to prevent incontinence.
AB  - This exploratory study assesses factors predicting adherence to a behavioral
      intervention to prevent urinary incontinence. Community-dwelling, post-menopausal
      women (N = 164) were taught pelvic floor muscle training (PFMT) and bladder
      training (BT) and followed with surveys for 1 year. Content analysis of open
      ended responses coded descriptions of approaches participants used to incorporate
      PFMT into daily life. Exploratory bivariate and logistic regression analyses
      determined predictors of approach used and adherence. Results indicate women
      incorporated PFMT into their lives using either a routine or ad hoc approach.
      Those using a routine approach at 3 months were 12 times more likely to adhere
      (odds ratio [OR] = 12.4, confidence interval [CI] = 4.0-38.8, p < .001) at a high
      level at 3 months and significantly more likely to maintain that level 12 months
      post-intervention (OR = 2.7, CI = 1.2-6.0, p < .014). Practicing BT was related
      to high adherence.

PMID- 17228061
TI  - Field notes and theoretical memos in grounded theory.
AB  - In this article the authors expose some of the mystique surrounding field notes
      and theoretical memos in a Glaserian grounded theory study. Definitions, types,
      and content of field notes and theoretical memos are presented. Exemplars from a
      study of mothers living with serious mental illness are provided to illustrate
      how these forms of documentation evolved during the course of the study. The
      authors argue that, although the processes of field noting and memoing may blur
      as a study progresses, they nevertheless retain their independent functions. The
      authors contend that without understanding the complementary function of these
      two types of documentation, data cannot evolve to a higher interpretive level.
      This article contributes specific ideas for improving the methods used by
      qualitative nurse researchers.

PMID- 17228062
TI  - Self-cognitions in antisocial alcohol dependence and recovery.
AB  - Cross-sectional relationships between content and structural properties of the
      self-concept and alcohol use in young adults with antisocial alcohol dependence
      (AAD) (n = 24), those in recovery from AAD (n = 18), and controls (n = 23) were
      examined using the schema model of the self-concept. Persons with AAD had a trend
      toward fewer positive self-schemas than did controls, and had more negative self
      schemas and a trend toward higher interrelatedness than did those in recovery and
      controls. They also showed evidence of a drinking-related self-schema, whereas
      those in recovery showed evidence of a recovery-related self-schema. Finally,
      evidence to support a model using properties of the self-concept to predict high
      levels of alcohol use was found. These findings provide a beginning empirical
      foundation for the development of nursing interventions aimed at altering self
      structure to prevent the development of and promote recovery from antisocial
      alcohol dependence.

PMID- 17228063
TI  - Health status in an invisible population: carnival and migrant worker children.
AB  - One goal of Healthy People 2010 (2003) is to close the gap of disparities in
      access to care and health. The purpose of this descriptive exploratory study was
      to evaluate health status indicators in the children of itinerant carnival and
      migrant farmworkers aged birth to 12 years. Health status outcomes (immunization
      records, well-child examinations, dental health status, and growth parameters)
      were compared between the two groups and to national averages to identify health
      disparities. All forms were available in Spanish and English. A total of 97
      children were recruited for this study: 45 carnival children and 52 migrant
      farmworker children.

PMID- 17228064
TI  - Balancing the needs of the scientist and the subject in trauma research.
AB  - All participants in research are vulnerable to some extent. Survivors of trauma
      are often sought as participants for research studies and may be at an increased
      risk of emotional or psychological distress as a result of research
      participation. Scientists need to pay careful attention to issues of informed
      consent and the potential harm and benefits from research participation. This
      article explores challenges of selecting a sample, informed consent, and study
      continuation when conducting research with survivors of trauma.

PMID- 17228066
TI  - Biological pacemaking: a concept whose time has come...or is coming.
AB  - "..when biological pacemakers reach clinical testing it is likely that some form
      of tandem therapy [with electronic pacemakers] will be used.."

PMID- 17228067
TI  - Underuse of revascularisation in acute coronary syndromes.
AB  - Is coronary revascularisation being underused in patients at highest risk, and
      overused in those at lower risk?

PMID- 17228068
TI  - Left ventricular pressure-volume loops during mechanical alternans in a patient
      with dilated cardiomyopathy.

PMID- 17228069
TI  - Retrograde coronary interventions of chronic total occlusions.

PMID- 17228070
TI  - A pretest prognostic score to assess patients undergoing exercise or
      pharmacological stress testing.
AB  - OBJECTIVE: A previously developed pretest score was validated to stratify
      patients presenting for exercise testing with suspected coronary disease
      according to the presence of angiographic coronary disease. Our goal was to
      determine how well this pretest score risk stratified patients undergoing
      pharmacological and exercise stress tests concerning prognostic endpoints.
      DESIGN: Retrospective cohort analysis. SETTING: University hospital stress
      laboratory. PATIENTS: 7452 unselected ambulatory patients with symptoms of
      suspected coronary disease undergoing stress testing between 1995 and 2004. MAIN
      OUTCOMES MEASURES: All-cause death, cardiac death and non-fatal myocardial
      infarction. RESULTS: The rate of all-cause death was 5.5% (CI 5.0 to 6.1) with
      4.3 (SD 2.4) years of follow-up (Exercise 2.8% (CI 2.3 to 3.2) v Pharmacological
      group 11.9% (CI 10.5 to 13.3); p<0.001). The rate of cardiac death/myocardial
      infarction was 2.6% (CI 2.2 to 3.0) (Exercise 1.4% (CI 1.1 to 1.8) v
      Pharmacological group 5.3% (CI 4.3 to 6.2); p<0.001). In both groups,
      stratification by pretest score was significant for all-cause death and the
      combined endpoint. However, stratification was more effective in the
      pharmacological group using the combined endpoint rather than all-cause death.
      Pharmacological stress patients in intermediate and high risk groups were at
      higher risk than their respective exercise test cohorts. Referral for
      pharmacological stress testing was found to be an independent predictor of time
      to death (2.7 (CI 2.0 to 3.6); p<0.001). CONCLUSION: A pretest score previously
      validated to stratify according to angiographic outcomes, effectively risk
      stratified pharmacological and exercise stress patients according to the combined
      endpoint of cardiac death/myocardial infarction.

PMID- 17228071
TI  - Spontaneous coronary vasospasm in the catheterisation laboratory: prompt
      resolution after atropine injection.

PMID- 17228073
TI  - Free-floating left atrial thrombus formed in a few weeks in a patient with a
      normal mitral prosthesis.

PMID- 17228072
TI  - Coronary artery-left atrial fistula caused by feeding artery rupture in cardiac
      myxoma.

PMID- 17228075
TI  - Haemodynamic significance of ostial side branch nipping following percutaneous
      intervention at bifurcations: a pressure wire pilot study.

PMID- 17228074
TI  - Carvedilol improves endothelium-dependent vasodilation in patients with dilated
      cardiomyopathy.

PMID- 17228076
TI  - Targeting drug-eluting stents to lesions at high risk of restenosis: a flawed
      approach?

PMID- 17228077
TI  - The effects of the angiotensin II receptor (type I) antagonist irbesartan in
      patients with cardiac syndrome X.

PMID- 17228078
TI  - Relation between nitric oxide metabolites and haemoglobin concentrations in
      patients with ischaemic heart disease.

PMID- 17228079
TI  - Antiplatelet treatment for coronary heart disease.

PMID- 17228080
TI  - Diagnosis and management of patients with aortic dissection.

PMID- 17228081
TI  - Management of tricuspid valve regurgitation.

PMID- 17228082
TI  - Repetitive activation of glutamatergic inputs evokes a long-lasting excitation in
      rat globus pallidus neurons in vitro.
AB  - External globus pallidus (GPe) neurons express abundant metabotropic glutamate
      receptor 1 (mGluR1) in their somata and dendrites and receive glutamatergic
      inputs mainly from the subthalamic nucleus. We investigated whether synaptically
      released glutamate could activate mGluR1s using whole cell and cell-attached
      recordings in rat brain slice preparations. Repetitive internal capsule
      stimulation evoked EPSPs followed by a slow depolarizing response (sDEPO) lasting
      10-20 s. Bath application of both GABA(A) and GABA(B) receptor antagonists
      increased the amplitude of sDEPOs. A mixture of AMPA/kainate and N-methyl-d
      aspartate receptor antagonists did not alter sDEPOs. The induction of sDEPOs was
      only partially mediated by mGluR1 because mGluR1 antagonists reduced but failed
      to completely block the responses. Voltage-clamp recordings revealed that slow
      inward currents sensitive to mGluR1 antagonist were larger at -60 than at -100
      mV, whereas the currents insensitive to mGluR1 antagonist were larger at -100
      than at -60 mV. In cell-attached recordings, repetitive internal capsule
      stimulation evoked long-lasting excitations in GPe neurons, which were also
      partially suppressed by mGluR1 antagonists. Application of a glutamate uptake
      inhibitor or an mGluR1 agonist significantly increased the spontaneous firing
      rate but decreased the excitations to repetitive stimulation. These results
      suggest that synaptically released glutamate can activate mGluR1, contributing to
      the induction of long-lasting excitation in GPe neurons and that background
      mGluR1 activation suppresses the slow mGluR1 responses. Thus mGluR1 may play
      important roles in the control of GPe neuronal activity.

PMID- 17228084
TI  - Central regulation of food intake in ageing.
AB  - Energy homeostasis and fuel metabolism undergo significant modifications in the
      course of ageing. During the second half of life many humans increase their body
      mass and develop glucose intolerance that may lead to obesity and type 2
      diabetes. However, many old people suffer from being underweight, and this
      "anorexia of elderly" may seriously compromise their health under certain
      circumstances. Experimental studies into the causes of ageing-related impairments
      of food intake regulation were performed mainly on rat, and to some extent, on
      non-human primates. It was found that the expression of NPY, the most potent
      orexigenic peptide, and of NPY receptors, is highly suppressed in the
      hypothalamus of old rats. Moreover, the increase of NPY mRNA after fasting was
      severely blunted in old as compared to young rats. Similar reductions, although
      of lower magnitude, were reported for other hypothalamic orexigenic compounds
      such as, AgRP and orexins. Interestingly, ageing does not significantly alter
      hypothalamic mRNA levels of important anorexigens such as CART and aMSH. The
      presented findings suggest that, at least in rodents, ageing is associated with
      the general down-regulation of hypothalamic peptides that stimulate food intake
      and unchanged expression of anorexigenic peptides. This situation may be
      responsible for the decreased appetite drive in senescent animals and loss of
      weight at the end-of-life period. If similar changes of the central control of
      food intake underly "anorexia of ageing" observed in some elderly, it is possible
      that therapeutic intervention at this regulatory level may be possible in the
      future.

PMID- 17228083
TI  - Autonomic control network active in Aplysia during locomotion includes neurons
      that express splice variants of R15-neuropeptides.
AB  - Splice-variant products of the R15 neuropeptide gene are differentially expressed
      within the CNS of Aplysia. The goal of this study was to test whether the neurons
      in the abdominal ganglion that express the peptides encoded by this gene are part
      of a common circuit. Expression of R15 peptides had been demonstrated previously
      in neuron R15. Using a combination of immunocytochemical and analytical methods,
      this study demonstrated that R15 peptides are also expressed in heart exciter
      neuron RB(HE), the two L9(G) gill motoneurons, and L40--a newly identified
      interneuron. Mass spectrometric profiling of individual neurons that exhibit R15
      peptide-like immunoreactivity confirmed the mutually exclusive expression of two
      splice-variant forms of R15 peptides in different neurons. The L9(G) cells were
      found to co-express pedal peptide in addition to the R15 peptides. The R15
      peptide-expressing neurons examined here were shown to be part of an autonomic
      control circuit that is active during fictive locomotion. Activity in this
      circuit contributes to implementing a central command that may help to coordinate
      autonomic activity with escape locomotion. Chronic extracellular nerve recording
      was used to determine the activity patterns of a subset of neurons of this
      circuit in vivo. These results demonstrate the potential utility of using shared
      patterns of neuropeptide expression as a guide for neural circuit identification.

PMID- 17228086
TI  - The effect of orexins on intestinal motility in vitro in fed and fasted rats.
AB  - Orexin-A and -B (OXA, OXB) are peptides involved in many gastrointestinal (GI)
      functions, including motility. Orexins, their precursors and receptors are
      present in the GI tract. The expression of orexins increases in the hypothalamus
      and gastrointestinal tract in response to fasting. We have examined the effect of
      OXA and OXB on GI motility in vitro in fed and fasted rats. The intestinal
      segments were mounted in chambers filled with Krebs solution. Isotonic
      contractions were measured in response to acetylcholine (10(-5) M), electric
      field stimulation (EFS), and orexins (10(-9)-10(-7) M) alone or in the presence
      of orexin-1 type receptor antagonist, SB- 334867 (10(-5) M), tetrodotoxin (TTX)
      10(-6) M, or atropine (10(-5) M). Orexins caused a dose-dependent increase of
      intestinal segment contractions with a more pronounced effect of OXB over OXA.
      Fasting did not influence orexin-induced responses. Incubation with SB-334867 led
      to a marked decrease in orexin-induced contractions in OXA-treated segments,
      while those of OXB were not affected. Atropine diminished contractions only in
      fasted animals, while TTX led to a decreased response to orexins in both groups.
      The results show that OXB is predominant in inducing gut motility response, that
      the effect of orexins is not fully dependent on cholinergic and Na(+)
      transmissions, and that involvement of other transmitters is possible.

PMID- 17228085
TI  - Central and local (enteric) action of orexins.
AB  - Orexin-A (OXA, hypocretin-1) and orexin-B (OXB, hypocretin-2) are peptides
      derived from the same 130 amino acid long precursor (prepro-orexin) that bind and
      activate two closely related orphan G protein-coupled receptors. Orexins and
      their receptors were first discovered in the rat brain, and soon after that in
      peripheral neural structures, including the vagal nerve and enteric nervous
      system, and in other structures involving the gastrointestinal tract diffuse
      neuroendocrine system, pancreas tissue, stomach and intestinal mucosa. Orexins
      and their receptors were also demonstrated in the testes, adrenals, kidneys, and
      placenta. This review is focused on central and enteric actions. Originally,
      orexins were considered to be neurotransmitters that centrally stimulate food
      intake in animals and humans, but it soon became evident that their action is
      broader due to activation of a large number of neuronal pathways involved in
      energy homeostasis, sleep-awake behavior, nociception reward seeking, food and
      drug addiction, as well as reproduction, cardiovascular and adrenal function. In
      the gastrointestinal tract, orexins have been found so far to affect
      gastrointestinal motility and gastric, intestinal and pancreatic secretions. The
      effects were observed following central (intraventricular) or local
      (intraluminal, intraarterial), but not peripheral (intravenous), administrations
      of orexins. Since the expression of orexins in the gastrointestinal tract is
      enhanced during fasting, and fasting reveals many of the orexin gastrointestinal
      effects, it seems probable that on the local level, orexins keep the
      gastrointestinal tract functions ready during fasting and play role in brain-gut
      axis control.

PMID- 17228088
TI  - Neural aspects of ghrelin-induced gastroprotection against mucosal injury induced
      by noxious agents.
AB  - Ghrelin, identified in oxyntic mucosa has been recently implicated in the control
      of food intake and growth hormone (GH) release but whether this hormone can
      influence the gastric secretion and gastric mucosal integrity have been little
      studied. We compared the effects of intraperitoneal (i.p.) and
      intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion
      in rats equipped with gastric fistula (GF) and gastric lesions induced in rats by
      75% ethanol and ischemia-reperfusion (I/R) with or without vagotomy or functional
      ablation of afferent sensory nerves by capsaicin. The number and the area of
      gastric lesions was measured by planimetry, the GBF was assessed by H(2)-gas
      clearance method and blood was withdrawn for the determination of the plasma
      ghrelin and gastrin levels. Ghrelin (5-80 microg/kg i.p. or 600-5000 ng/rat
      i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced
      by ethanol and I/R. These protective effects of ghrelin were accompanied by the
      significant rise in the gastric mucosal blood flow (GBF) and plasma ghrelin and
      gastrin levels. Ghrelin given i.p. or injected i.c.v. in standard doses 20
      microg/kg or 5000 ng/kg, respectively, significantly attenuated the gastric
      mucosal damage and significantly raised the GBF. Ethanol applied i.g. in smaller
      concentrations (12.5% and 25%) produced a significant increase in plasma
      immunorective ghrelin levels and this effect was inhibited in rats receiving
      ethanol in higher concentrations (75% and 100%). Ghrelin-induced protection after
      its i.p. or i.c.v. administration and accompanying increase in the GBF were
      completely abolished by vagotomy and capsaicin-deactivation of sensory nerves.
      Concurrent treatment with CGRP added to ghrelin restored the gastroprotective and
      hyperemic effects of ghrelin applied i.p. or i.c.v. in rats with capsaicin
      denervation. We conclude that central and peripheral ghrelin exerts a potent
      protective and gastric secretory effects in rats exposed to ethanol and I/R, and
      that these actions involve vagal nerve integrity, partially depending upon
      afferent nerves and hyperemia mediated by sensory neuropeptides such as CGRP
      released from these nerves.

PMID- 17228087
TI  - Neuroendocrine control of metabolic homeostasis in Polish centenarians.
AB  - Neuropeptides play a pivotal role in the control of metabolic homeostasis. We
      aimed to evaluate the release of neuropeptides involved in the control of energy
      homeostasis in relation to metabolic status in aging humans. The study group
      consisted of 183 women: 75 centenarians (above 100 yrs old), 26 elderly women
      (below 70 yrs), 45 younger women (mean 26 yrs) and 37 obese women (mean 41.6
      yrs). Fasting plasma concentration of leptin, adiponectin, ghrelin active,
      neuropeptide Y (NPY) and insulin were measured. Our results showed several
      differences in the metabolic and neurohormonal status in the centenarian group.
      The incidence of hypertension, glucose intolerance, insulin resistance and
      dyslipidemia was lower compared with obese women. Leptin and NPY concentrations
      were significantly lower than in elderly and obese subjects. Moreover, NPY level
      was higher than that in the younger group. Plasma adiponectin values were higher
      than in any of the other group. Insulin levels were significantly lower compared
      with the young and obese groups. Furthermore, a negative correlation was found
      between adiponectin and HOMA-IR, and adiponectin and insulin. Ghrelin active
      concentrations were significantly lower compared with the young subjects.
      However, ghrelin levels were higher than in obese subjects. We conclude that
      altered neuropeptide activity in centenarians may play a role in the mechanisms
      contributing to prolonged survival.

PMID- 17228089
TI  - The effects of fasting and refeeding on adrenal cortex morphometry and serum
      concentrations of ACTH and corticosterone in young and old male rats.
AB  - The impairment of homeostatic mechanisms in ageing becomes often apparent upon
      physiological or pathological stimulation. We have previously shown that fasting
      and refeeding revealed the existence of age-related changes of carbohydrate and
      lipid metabolism. Because fuel metabolism is partially controlled by
      corticosteroids we decided to determine the effects of refeeding on adrenal gland
      morphometry, ACTH, and corticosterone serum levels in young (5 mo) and (20 mo)
      old male Wistar rats. Fasting for 48 h did not change serum ACTH and
      corticosterone in both age groups. ACTH level did not change after 24 h of
      refeeding in young and old rats. However, in old, but not young animals,
      refeeding resulted in the decrease of corticosterone serum concentration. The
      relative weight of adrenal gland (% of body weight) did not change significantly
      with age (p=0.05). Fasting for 48 h induced in old rats but not in young ones
      increase of relative adrenal weight, and the volume of the reticular zone.
      Refeeding reduced adrenal volume, fascicular zone and reticular zone. Refeeding
      for 24 h decreased the total volume of adrenal gland of old rats due to a decline
      of the volumes of fascicular and reticular zones. In young rats refeeding reduced
      the volume of reticular zone. It is concluded that refeeding revealed ageing
      dependent decline in the secretion of corticosterone, the key hormone of
      prolonged stress response.

PMID- 17228090
TI  - Leptin and age-related down-regulation of lipogenic enzymes genes expression in
      rat white adipose tissue.
AB  - The age-related inverse relationship between gene expression of lipogenic enzymes
      and leptin gene expression as well as inhibitory effect of leptin on lipogenic
      enzyme's gene expression suggest that leptin could be responsible in part for the
      low rate of lipogenesis in white adipose (WAT) of old rats. Based on the data
      published recently we propose a model for the direct inhibitory effect of leptin
      on lipogenesis. This model may explain the age-related decrease of lipogenic
      activity in WAT. It is likely that despite of higher concentration of
      noradrenaline (which inhibits leptin gene expression in WAT) in old animals, the
      age-dependent decrease of beta-adrenergic receptor density in rat adipocytes may
      lead to the increase of leptin gene expression and to the increase of WAT leptin
      concentration. High concentration of leptin in adipose tissue decreases sterol
      regulatory element binding protein-1 (SREBP-1) gene expression by paracrine
      and/or autocrine action on adipocyte, which leads to the decrease of SREBP-1c
      level (mature form). The suppression of SREBP-1c synthesis causes a decrease of
      lipogenic enzyme's gene expression which consequently results in lower rate of
      fatty acid synthesis in WAT. This model does not exclude the indirect, via
      hypothalamus (by decreasing food consumption), inhibitory action of leptin on WAT
      lipogenesis. Therefore, it is likely that leptin exerts its inhibitory effect on
      WAT lipogenesis both directly at the level of adipocytes, and indirectly through
      hypothalamus by decreasing food intake. The inhibitory effect of of high leptin
      concentration on lipogenesis in WAT of old rats could prevent over-accumulation
      of triacylglycerols in adipocyte, and by this way could protect against further
      development of the fat mass.

PMID- 17228091
TI  - Role of adiponectin in the regulation of carbohydrate and lipid metabolism.
AB  - Adiponectin, an adipocyte-derived plasma protein, has been shown to play an
      important role in the regulation of fatty acid and glucose metabolism.
      Adiponectin enhances fatty acid oxidation both in skeletal and cardiac muscle as
      well as in the liver, thus reducing triglyceride content in these tissues.
      Moreover, it stimulates glucose uptake by skeletal and cardiac muscle, and
      inhibits glucose production by the liver; consequently decreasing blood glucose
      levels. This review focuses on the molecular mechanisms underlying adiponectin
      effects on carbohydrate and lipid metabolism in skeletal muscle, cardiac muscle
      and liver.

PMID- 17228092
TI  - The effects of weight cycling on serum leptin levels and lipogenic enzyme
      activities in adipose tissue.
AB  - Weight cycling is one of the widely used weight reduction strategies; however,
      the adverse effects of this method include regaining significant amounts of
      weight. The molecular mechanisms underlying weight gain following cycles of
      dietary deprivation and refeeding are still poorly understood. One of the
      possibilities is that repeated loss and gain of weight may promote fat deposition
      in adipose tissue. To test this hypothesis we investigated serum leptin levels
      and lipogenic enzyme activities in white adipose tissue (WAT) of male Wistar rats
      during 12 days of ad libitum feeding following multiple cycles of alternating
      food deprivation and refeeding. Rats subjected to eight cycles of food
      deprivation and refeeding (MFR group) showed significantly decreased circulating
      leptin levels when compared with control rats (nearly 50% decrease in leptin
      levels, P < 0.01). Throughout 12 days of ad libitum feeding, serum leptin levels
      increased modestly but remained significantly (24%, P < 0.05) lower than control
      levels. Fatty acid synthase (FAS) and malic enzyme (ME) activities (chosen as
      representatives of enzymes directly involved in fatty acid synthesis) were found
      to be considerably higher in WAT of MFR rats refed for 3 days in comparison to
      control rats, and remained elevated even after 12 days of refeeding. These
      observations suggest that the elevation of lipogenic enzyme activities induced by
      multiple cycles of dietary deprivation followed by refeeding persists for several
      days, markedly increasing the lipogenic capacity of adipose tissue, which,
      accompanied by a decrease in circulating leptin levels, may promote weight gain.

PMID- 17228093
TI  - Stem cells as a two edged sword--from regeneration to tumor formation.
AB  - Evidence has accumulated that quiescent stem cells or cells developmentally
      closely related to them distributed in various organs may be a cellular origin of
      cancer development. In support of this notion, stem cells (SC) are long-lived
      cells with distinctive properties of self-renewal and has the potential to
      proliferate extensively. Given these features, it's possible that they may become
      the subject of consecutive accumulated mutations that are crucial for initiation
      of cancer. Therefore, mutations that occur in normal stem cells might lead to
      their malignant transformation and tumor initiation. Furthermore, many biological
      features of normal and cancer SC such as the physiological trafficking of normal
      and metastasis of cancer stem cells involve similar molecular mechanisms, and we
      discuss these similarities here.

PMID- 17228094
TI  - Apoptosis and autophagy in mammary gland remodeling and breast cancer
      chemotherapy.
AB  - Apoptosis - programmed cell death (PCD) type I is physiological process
      responsible for cell loss during mammary gland involution after natural weaning
      or litter removal in rodents, after weaning in sow and during drying off in goat
      and cow. The regulation of mammary epithelial cell (MEC) apoptosis in bovine
      mammary gland occurs at three levels. The first level comprises intracellular
      regulatory proteins, e.g. Bcl-2 family death promoters and inhibitors. The second
      level is represented by intramammary inductors of apoptosis, e.g. FIL, IGFBPs,
      Fas ligand, TGF-betas. The expression and activity of these auto/paracrine
      inductors of apoptosis is controlled and modulated by the third level factors,
      e.g. systemic galactopoetic hormones, nutrition, reproductive status and milking
      management. Our recent study proved that apoptosis in involuting bovine mammary
      gland is accompanied by increased intensity of autophagy, regarded as a
      cytoprotective process but in advanced stage as a PCD type II. Moreover, we have
      reported for the first time the ability of TGF-beta(1) to induce both apoptosis
      and autophagy in bovine BME-UV1 MEC. Much more pronounced heterogeneity of PCD
      was observed when breast cancer cells were exposed to anticancer drugs. The
      primary responses of breast cancer MCF-7 cells to camptothecin (CPT) are
      apoptosis and autophagy (as a cytoprotective process). In this case autophagy
      occurs in cells which are resistant to apoptosis as a tool of cancer cell
      survival. The fail-safe responses of breast cancer cells to persisting CPT
      induced stress are apoptosis accompanied by morphological and biochemical
      features of autophagy or type II PCD with advanced subcellular degradation. The
      threshold between autophagy as a cytoprotective process (reversible) or PCD
      (irreversible) is difficult to establish and probably depends on the extent of
      degradation of cellular components. Proapoptotic protein Bid may serve as a
      molecular switch between apoptosis and autophagy. Bid knock down in MCF-7 cells
      exposed to CPT leads to a shift of cell death from apoptosis to autophagy. Since
      bid and other proapoptotic genes undergo mutations in malignant cells, the
      ability of cancer cells commitment to autophagy may have important therapeutic
      implications.

PMID- 17228095
TI  - Modulation of oxidative DNA damage repair by the diet, inflammation and
      neoplastic transformation.
AB  - Oxidative DNA damage and DNA repair may mediate several cellular processes, like
      replication and transcription, mutagenesis and apoptosis and thus may be
      important for the organism development as well as its pathogenesis, including
      cancer. Activity of DNA repair enzymes can depend on many factors, such as gene
      polymorphism, mRNA and protein level, as well as enzymes activation and
      inhibition. Modulation of base excision repair pathway eliminating from DNA
      oxidatively formed lesions may be caused by the diet, inflammation and neoplastic
      transformation. Reactive oxygen species and some diet components induce
      transcription of several Base Excision Repair enzymes, e.g. major human AP
      endonuclease, (APE1) and 8-oxoG-DNA glycosylase (OGG1). The carcinogenic process
      in human lung decreases repair activity for 8-oxoGin transcription independent
      manner, but increases repair activity of epsilon A and epsilon C, as measured in
      tumors and unchanged lung tissues of lung cancer patients. Thus, modulation of
      repair enzymes activities may be a cell response on their way to differentiation
      ot neoplastic transformation.

PMID- 17228096
TI  - Apical NA+/H+ exchangers in the mammalian gastrointestinal tract.
AB  - The Slc9a family of nine Na(+)/H(+) exchangers (NHE) plays a critical role in
      neutral sodium absorption in the mammalian intestine as well as other absorptive
      and secretory epithelia of digestive organs. These transport proteins mediate the
      electroneutral exchange of Na(+) and H(+) and are crucial in a variety of
      physiological processes, including the fine tuning of intracellular pH, cell
      volume control and systemic electrolyte, acid-base and fluid volume homeostasis.
      Here, we review the role of the Na(+)/H(+) exchange mechanism as it relates to
      the physiology of organs and cells involved in nutrient absorption, and we
      describe physiological and molecular aspects of individual isoforms, including
      their structure, tissue-, and subcellular distribution, as well as their
      regulation by physiological stimuli at the transcriptional and post
      transcriptional levels. A particular emphasis is placed on Na(+)/H(+) exchanger
      isoforms expressed on the apical (brush border) membrane of the epithelial cells,
      and the consequences of gene-targeted mutation of individual isoforms are
      discussed in the context of the physiology of digestive organs. Where available,
      we also provide a review of pathophysiological states related to aberrant
      expression and/or activity of Na(+)/H(+) exchangers within the confines of the
      digestive system.

PMID- 17228097
TI  - Plasma proteome analysis: 2D gels and chips.
AB  - The knowledge of concentration, modification and interaction of proteins is
      fundamental in determining the phenotype of living organisms. Plasma, the primary
      clinical specimen, contains numerous and diverse proteins. The functions of these
      proteins are as manifold as the diversity of the protein themselves. Many of them
      have been largely used for many years as biomarkers of diseases and indicators of
      the physiological functions. The study of plasma proteome promises to be a
      significant advance in various areas of biological and clinical research. Two
      dimensional polyacrylamide gel electrophoresis is considered as a primary tool in
      separating thousand of plasma proteins. This approach enables comparing normal
      and diseased samples revealing differently expressed proteins. Other proteomic
      techniques suitable for plasma analysis such as protein microarrays are now
      either established or are still being improved. This article briefly reviews the
      application of two-dimensional electrophoresis and the current status of
      technical aspects for plasma proteome.

PMID- 17228099
TI  - Actin cytoskeleton and beta-actin expression in correlation with higher
      invasiveness of selected hepatoma Morris 5123 cells.
AB  - Our studies were focused on the isolation and characterization of highly motile
      fraction of cells from hepatoma Morris 5123 population. Cells that underwent
      several migration cycles through Matrigel - coated filters were successfully
      cultured. The invasion index was determined by means of Matrigel invasion assay.
      Statically significant increase in the value of invasion factor for selected
      cells variant in comparison to the parental population was observed. The
      considerable changes in the cell shape were followed by the reorganization of the
      actin cytoskeleton structure including a dense subcortical congestion in the
      distribution of beta -actin isoform. The visualization of this protein in tumor
      cells was performed by immunostaining and scanning fluorescent confocal
      microscopy. The results were confirmed by densitometry analysis of Western blots.
      In addition, the increased state of actin polymerization in the cytoplasmic
      fraction of selected cells was determined as measured by filamentous to monomeric
      (F:G) actin ratio. Concluding, the selected fraction of hepatoma Morris 5123
      cells with higher invasion capacity was characterized by rounded shape,
      remarkable increase of beta -actin level, its submembrane concentration as well
      as with the increased state of actin polymerization with respect to parental
      cells population.

PMID- 17228100
TI  - Quantitative study of soybean-induced changes in proliferation and programmed
      cell death in the intestinal mucosa of young rats.
AB  - The use of soybean in human and animal nutrition is limited because of high
      content of bioactive compounds: enzyme inhibitors, polyphenols, goitrogens,
      phytates, saponins, sugars, and agglutinins. The damage of intestinal mucosa
      structure was previously observed in animals fed soybean supplemented diets.
      Hence, the objectives of the presented study were to compare intensity of
      epithelium remodeling processes in different intestinal segments, and to evaluate
      the influence of the 1% of soybean dietary supplementation on the processes in
      intestinal mucosa. The experiment was performed on 30 Wistar rats fed AIN-93
      based diets. Animals were divided randomly into three groups: control (CTRL),
      with 1% of raw soybean (RS) and with 1% of soaked and boiled soybean (BS). The
      samples of: duodenum (DUO), proximal jejunum (PROX), mid-jejunum (MID), distal
      jejunum (DIST) and ileum (ILE) were collected. The following processes in these
      samples were evaluated: mitosis (Ki-67), apoptosis (Cpp32), autophagy (MAP I LC3)
      and DNA damage (p53). Present data show that modification of soybean by soaking
      and subsequent boiling markedly influences the enterocyte turnover in the small
      intestine mucosa. Increased mitotic ratio in the intestine of rats fed with
      boiled soybean masks the negative effects of soybean on the small intestine
      structure.

PMID- 17228098
TI  - Age-dependent changes in bovine skeletal muscle transcriptomic profile.
AB  - The postnatal growth of muscle tissue occurs by hypertrophy comprising satellite
      cells proliferation, differentiation and protein turnover. The highest rate of
      skeletal muscle gains and protein synthesis in bulls occurs in the period between
      180 and 360 days of postnatal life. However, genes which are responsible for
      quantitative and qualitative changes in skeletal muscle during this period are
      not identified up to date. The aim of our study was to compare the changes in
      transcriptomic profile of skeletal muscle (m. semitendinosus) in 12 Polish Black
      and White bulls between 6 and 12 month of life. For experimental purposes we used
      bovine cDNA microarray (the NBFGC EST collection) which contains 18,263 unique
      genes, derived from many different tissue types and various physiologically
      important states within these tissues. Our results revealed 53 genes which
      expression changed in the same manner depending on age of all examined pairs of
      animals. Thirty two of these genes showed at least 2-fold difference in
      expression between two analyzed age points. Age-dependent up-regulation was the
      most pronounced in the case of following genes: similar to MAD2L1 binding
      protein, similar to thymocyte protein thy28 isoform 1, similar to type I inositol
      1,4,5-triphosphate 5-phosphatase, similar to nucleoside diphosphate kinase 6,
      proline rich 14, similar to transcription factor E2-alpha and phospholipase C
      gamma 1. The highest age-dependent decrease of the transcript was observed in the
      case of: similar to ubiquitin carboxy-terminal hydrolase L1, similar to latent
      TGF-beta binding protein 3 precursor, phospho-mannomutase 2, CD74 antigen,
      similar to BCL6 co-repressor-like 1, platelet/endothelial cell adhesion molecule
      (PECAM1), necdin, zygin, tight junction protein 3, ankyrin and apolipoprotein-L3.
      Although the role of the most of above genes and interactions between products of
      their expression is not clear at the moment, the significance of their response
      between 6 and 12 month of age may indicate their involvement in growth,
      development and metabolic changes in bovine skeletal muscle during the first year
      of postnatal life.

PMID- 17228101
TI  - Leptin is the modulator of HSP60 gene expression in AR42J cells.
AB  - Leptin, circulating protein involved in the control of body weight and energy
      expenditure received attention as a modulator of immune response of the organism.
      Leptin receptors have been detected in the pancreas and experimental studies have
      shown that leptin protects the pancreas against the damage induced by caerulein
      overstimulation. Heat shock proteins (HSP) are endogenous proteins produced by
      various cells exposed to high temperature or to the noxious agents. HSP protect
      the cells against various environmental and endogenous stressors. The implication
      of HSP60 in the leptin-induced pancreatic protection has not been examined yet.
      The aim of this study was: to investigate the changes of HSP60 mRNA signal in the
      pancreatic AR42J cells subjected to caerulein and leptin. AR42J cells were
      incubated in standart medium at 37 degrees C for: 0, 1, 3, 5, 12 or 24 h, under
      basal conditions. Incubation time of 3 h was selected for the next experiments.
      AR42J cells were incubated in presence of caerulein (10(-11), 10(-9) or 10(-7)
      M), leptin (10(-8) or 10(-6) M), or combination of above. Gene expression for
      HSP60 was determined by RT-PCR. The mRNA signal for HSP60 has been observed in
      AR42J pancreatic cells under basal conditions. Incubation of AR42J cells in
      presence of leptin (10(-8) or 10(-6) M) resulted in the significant increase of
      gene expression for HSP60 in both groups of AR42J cells. Caerulein stimulation
      reduced mRNA signal for HSP60. The strongest mRNA signal for HSP60 has been
      observed after the exposition of AR42J cells to combination of leptin and
      caerulein. We conclude that: 1. Gene expression for HSP60 has been detected in
      pancreatic AR42J cells under basal conditions. 2. HSP60 gene expression was
      significantly increased in pancreatic AR42J cells stimulated by leptin whereas
      caerulein reduced this signal. 3. The strongest gene expression for HSP60 has
      been detected in the cells incubated with combination of caerulein and leptin.

PMID- 17228102
TI  - In vivo and in vitro effects of hyperglycemia on Na+ -K+, Ca+2, Mg+2-dependent
      ATPases activity in brain synaptosomes of aging rats.
AB  - Cerebral metabolism of glucose, one of the determinants of tissue ATP level, is
      crucial for the CNS function. The activity of P-type pumps: Na(+), K(+)-ATPase,
      Ca(+2)-ATPase and Mg(+2)-ATPase were examined in rat brain synaptosomes to
      determine if changes in the enzyme activity related to aging are potentially
      associated with alterations in glucose homeostasis. Male Wistar rats (newborn, 3-
      and 18-month-old) were sacrificed by decapitation and synaptic plasma membranes
      were isolated from brains. In vivo study demonstrated that 18-month-old rats were
      characterized by hyperglycemia, hyperinsulinemia and increased total
      antyoxidative status (TAS) level. These conditions had a different impact on
      activities of the ATPases tested in vivo: only the activity of Ca(+2)-ATPase
      decreased whereas that of Mg(+2)-ATPase increased significantly. In vitro
      experiments, prior incubation of isolated synaptosomes with glucose of
      concentrations corresponding to normoglycemia in vivo (4.5 - 6.5 mM), stimulated
      Ca(+2)-ATPase activity, whereas higher glucose concentrations (10.0 - 12.5 mM)
      inhibited significantly the enzyme activity. The most sensitive to hyperglycemia
      appeared Na(+), K(+)-ATPase in old rats synaptosomes with the progressive decline
      starting at 6.5 mM glucose. The activity of Mg(+2)-ATPase was not inhibited in
      vitro even at high glucose concentrations that may explain the increased in vivo,
      activity of this enzyme in old, hyperglycemic rats.

PMID- 17228103
TI  - A positive contrast, tri-modality tissue marker for breast tumour localization.
AB  - A new interstitial breast localization marker is proposed which exhibits positive
      contrast in T1-weighted MRI, ultrasound and x-ray mammography. Unlike previous
      markers which provide MRI contrast on the basis of a susceptibility-induced
      signal void, this marker provides a clear positive contrast without any loss of
      signal or spatial distortion. The marker is composed of 400 microm diameter
      copper microspheres suspended in a Gd-DTPA-doped gel matrix. Optimal contrast in
      T1-weighted spoiled gradient recalled MRI was found to occur with the addition of
      10 mM Gd-DTPA. Ultrasound contrast was generated on the basis of scattering from
      the copper microspheres. X-ray contrast was provided by the high x-ray
      attenuation properties of the copper microspheres. The study demonstrates
      potential suitability of the marker for use as a breast localization marker based
      on ex vivo studies of chicken breast.

PMID- 17228104
TI  - Conversion of CT numbers into tissue parameters for Monte Carlo dose
      calculations: a multi-centre study.
AB  - The conversion of computed tomography (CT) numbers into material composition and
      mass density data influences the accuracy of patient dose calculations in Monte
      Carlo treatment planning (MCTP). The aim of our work was to develop a CT
      conversion scheme by performing a stoichiometric CT calibration. Fourteen
      dosimetrically equivalent tissue subsets (bins), of which ten bone bins, were
      created. After validating the proposed CT conversion scheme on phantoms, it was
      compared to a conventional five bin scheme with only one bone bin. This resulted
      in dose distributions D(14) and D(5) for nine clinical patient cases in a
      European multi-centre study. The observed local relative differences in dose to
      medium were mostly smaller than 5%. The dose-volume histograms of both targets
      and organs at risk were comparable, although within bony structures D(14) was
      found to be slightly but systematically higher than D(5). Converting dose to
      medium to dose to water (D(14) to D(14wat) and D(5) to D(5wat)) resulted in
      larger local differences as D(5wat) became up to 10% higher than D(14wat). In
      conclusion, multiple bone bins need to be introduced when Monte Carlo (MC)
      calculations of patient dose distributions are converted to dose to water.

PMID- 17228105
TI  - Full modelling of the MOSAIC animal PET system based on the GATE Monte Carlo
      simulation code.
AB  - Positron emission tomography (PET) systems dedicated to animal imaging are now
      widely used for biological studies. The scanner performance strongly depends on
      the design and the characteristics of the system. Many parameters must be
      optimized like the dimensions and type of crystals, geometry and field-of-view
      (FOV), sampling, electronics, lightguide, shielding, etc. Monte Carlo modelling
      is a powerful tool to study the effect of each of these parameters on the basis
      of realistic simulated data. Performance assessment in terms of spatial
      resolution, count rates, scatter fraction and sensitivity is an important
      prerequisite before the model can be used instead of real data for a reliable
      description of the system response function or for optimization of reconstruction
      algorithms. The aim of this study is to model the performance of the Philips
      Mosaic animal PET system using a comprehensive PET simulation code in order to
      understand and describe the origin of important factors that influence image
      quality. We use GATE, a Monte Carlo simulation toolkit for a realistic
      description of the ring PET model, the detectors, shielding, cap, electronic
      processing and dead times. We incorporate new features to adjust signal
      processing to the Anger logic underlying the Mosaic system. Special attention was
      paid to dead time and energy spectra descriptions. Sorting of simulated events in
      a list mode format similar to the system outputs was developed to compare
      experimental and simulated sensitivity and scatter fractions for different energy
      thresholds using various models of phantoms describing rat and mouse geometries.
      Count rates were compared for both cylindrical homogeneous phantoms. Simulated
      spatial resolution was fitted to experimental data for (18)F point sources at
      different locations within the FOV with an analytical blurring function for
      electronic processing effects. Simulated and measured sensitivities differed by
      less than 3%, while scatter fractions agreed within 9%. For a 410-665 keV energy
      window, the measured sensitivity for a centred point source was 1.53% and mouse
      and rat scatter fractions were respectively 12.0% and 18.3%. The scattered
      photons produced outside the rat and mouse phantoms contributed to 24% and 36% of
      total simulated scattered coincidences. Simulated and measured single and prompt
      count rates agreed well for activities up to the electronic saturation at 110 MBq
      for the mouse and rat phantoms. Volumetric spatial resolution was 17.6 microL at
      the centre of the FOV with differences less than 6% between experimental and
      simulated spatial resolution values. The comprehensive evaluation of the Monte
      Carlo modelling of the Mosaic system demonstrates that the GATE package is
      adequately versatile and appropriate to accurately describe the response of an
      Anger logic based animal PET system.

PMID- 17228106
TI  - Digimouse: a 3D whole body mouse atlas from CT and cryosection data.
AB  - We have constructed a three-dimensional (3D) whole body mouse atlas from
      coregistered x-ray CT and cryosection data of a normal nude male mouse. High
      quality PET, x-ray CT and cryosection images were acquired post mortem from a
      single mouse placed in a stereotactic frame with fiducial markers visible in all
      three modalities. The image data were coregistered to a common coordinate system
      using the fiducials and resampled to an isotropic 0.1 mm voxel size. Using
      interactive editing tools we segmented and labelled whole brain, cerebrum,
      cerebellum, olfactory bulbs, striatum, medulla, masseter muscles, eyes, lachrymal
      glands, heart, lungs, liver, stomach, spleen, pancreas, adrenal glands, kidneys,
      testes, bladder, skeleton and skin surface. The final atlas consists of the 3D
      volume, in which the voxels are labelled to define the anatomical structures
      listed above, with coregistered PET, x-ray CT and cryosection images. To
      illustrate use of the atlas we include simulations of 3D bioluminescence and PET
      image reconstruction. Optical scatter and absorption values are assigned to each
      organ to simulate realistic photon transport within the animal for
      bioluminescence imaging. Similarly, 511 keV photon attenuation values are
      assigned to each structure in the atlas to simulate realistic photon attenuation
      in PET. The Digimouse atlas and data are available at
      http://neuroimage.usc.edu/Digimouse.html.

PMID- 17228107
TI  - Reference tissue quantification of DCE-MRI data without a contrast agent
      calibration.
AB  - The quantification of dynamic contrast-enhanced (DCE) MRI data conventionally
      requires a conversion from signal intensity to contrast agent concentration by
      measuring a change in the tissue longitudinal relaxation rate, R(1). In this
      paper, it is shown that the use of a spoiled gradient-echo acquisition sequence
      (optimized so that signal intensity scales linearly with contrast agent
      concentration) in conjunction with a reference tissue-derived vascular input
      function (VIF), avoids the need for the conversion to Gd-DTPA concentration. This
      study evaluates how to optimize such sequences and which dynamic time-series
      parameters are most suitable for this type of analysis. It is shown that signal
      difference and relative enhancement provide useful alternatives when full
      contrast agent quantification cannot be achieved, but that pharmacokinetic
      parameters derived from both contain sources of error (such as those caused by
      differences between reference tissue and region of interest proton density and
      native T(1) values). It is shown in a rectal cancer study that these sources of
      uncertainty are smaller when using signal difference, compared with relative
      enhancement (15 +/- 4% compared with 33 +/- 4%). Both of these uncertainties are
      of the order of those associated with the conversion to Gd-DTPA concentration,
      according to literature estimates.

PMID- 17228108
TI  - Experimental spectral measurements of heavy K-edge filtered beams for x-ray
      computed mammotomography.
AB  - A dual modality computed mammotomography (CmT) and single photon emission
      computed tomography (SPECT) system for dedicated 3D breast imaging is in
      development. Using heavy K-edge filtration, the CmT component narrows the energy
      spectrum of the cone-shaped x-ray beam incident on the patient's pendant,
      uncompressed breast. This quasi-monochromatic beam is expected to improve
      discrimination of tissue with similar attenuation coefficients while restraining
      absorbed dose to below that of dual view mammography. Previous simulation studies
      showed the optimal energy that maximizes dose efficiency for a 50/50%
      adipose/glandular breast is between 30 and 40 keV. This study experimentally
      validates these results using pre-breast and post-breast spectral measurements
      made under tungsten tube voltages between 40 and 100 kVp using filter materials
      with K-edge values ranging from 15 to 70 keV. Different filter material
      thicknesses are used, approximately equivalent to the 200th and 500th attenuating
      value layer (VL) thickness. Cerium (K = 40.4 keV) filtered post-breast spectra
      for 8-18 cm breasts are measured for a range of breast compositions. Figures of
      merit include mean beam energy, spectral full-width at tenth-maximum, beam
      hardening and dose for the range of breast sizes. Measurements corroborate
      simulation results, indicating that for a given dose, a 200th VL of cerium
      filtration may have optimal performance in the dedicated mammotomography
      paradigm.

PMID- 17228109
TI  - A finite size pencil beam algorithm for IMRT dose optimization: density
      corrections.
AB  - For beamlet-based IMRT optimization, fast and less accurate dose computation
      algorithms are frequently used, while more accurate algorithms are needed to
      recompute the final dose for verification. In order to speed up the optimization
      process and ensure close proximity between dose in optimization and verification,
      proper consideration of dose gradients and tissue inhomogeneity effects should be
      ensured at every stage of the optimization. Due to their speed, pencil beam
      algorithms are often used for precalculation of beamlet dose distributions in
      IMRT treatment planning systems. However, accounting for tissue heterogeneities
      with these models requires the use of approximate rescaling methods. Recently, a
      finite size pencil beam (fsPB) algorithm, based on a simple and small set of
      data, was proposed which was specifically designed for the purpose of dose pre
      computation in beamlet-based IMRT. The present work describes the incorporation
      of 3D density corrections, based on Monte Carlo simulations in heterogeneous
      phantoms, into this method improving the algorithm accuracy in inhomogeneous
      geometries while keeping its original speed and simplicity of commissioning. The
      algorithm affords the full accuracy of 3D density corrections at every stage of
      the optimization, hence providing the means for density related fluence
      modulation like penumbra shaping at field edges.

PMID- 17228110
TI  - The influence of metal artefacts on the range of ion beams.
AB  - The influence of artefacts due to metal implants on the range of ion beams is
      investigated, using a geometrically well-defined head and pelvic phantom together
      with inserts from steel, titanium and tungsten. The ranges along various beam
      paths including artefacts were calculated from the TPS and compared to known
      calculations for phantoms without any insert. In the head phantom, beams
      intersecting the streak artefacts lead to errors in the range of around or below
      1%, which is mainly due to a cancellation of various effects. Beams through the
      metal or close to it show an underestimation of 3.5% of the range for tungsten.
      For the pelvic phantom, a large underestimation of the range is observed for a
      lateral path through the metal insert. In the case of tungsten and steel, range
      errors of -5% and -18% are observed, respectively. Such beam paths are typically
      used for pelvic tumours in radiotherapy with ion beams. For beams in the anterior
      posterior direction through the inserts, an overestimation of ion ranges of up to
      3% for titanium and 8% for steel is expected, respectively. Beam paths outside
      the metal insert show a large cancellation for the lateral beams (leading to
      errors of around 1% only) and somewhat higher errors for anterior-posterior beams
      (around 3% for titanium and 6% for steel). The analysis of CT data of patients
      with dental implants of gold as compared to patients with healthy teeth also
      showed a significant effect of the artefacts on the distribution of HU in the
      data, namely a redistribution of HU to higher and lower values as compared to
      patients with healthy teeth. The corresponding mean range variation was a 2.5%
      reduction in the data with artefacts as compared to the data without artefacts.
      It is concluded that beam paths through metal implants should generally be
      avoided in proton and ion therapy. In this case, the underestimation of ion range
      due to artefacts alone may amount to 3% for dental fillings and up to 5% and 18%
      for hip prosthesis made of titanium and steel, respectively. It is important to
      note that the size of the metal inserts cannot be determined correctly from the
      images, so that a correction of the ranges in metal also leads to large
      uncertainties. Finally, it should be stressed that the stated relative deviations
      are strictly valid only for the investigated phantoms and can only give a rough
      estimate on the size of range uncertainties that may appear in real patients.

PMID- 17228111
TI  - Variations in lithium target thickness and proton energy stability for the near
      threshold 7Li(p,n)7Be accelerator-based BNCT.
AB  - The usable range of thickness for the solid lithium target in the accelerator
      based neutron production for BNCT via the near-threshold (7)Li(p,n)(7)Be reaction
      was investigated. While the feasibility of using a (7)Li-target with thickness
      equal to that which is required to slow down a mono-energetic 1.900 MeV incident
      proton to the 1.881 MeV threshold of the (7)Li(p,n)(7)Be reaction (i.e., t(min) =
      2.33 microm) has already been demonstrated, dosimetric properties of neutron
      fields from targets greater than t(min) were assessed as thicker targets would
      last longer and offer more stable neutron production. Additionally, the
      characteristics of neutron fields generated by (7)Li(p,n)(7)Be for Gaussian
      incident protons with mean energy of 1.900 MeV were evaluated at a (7)Li-target
      thickness t(min). The main evaluation index applied in this study was the
      treatable protocol depth (TPD) which corresponds to the depth in an irradiated
      medium that satisfies the requirements of the adapted dose protocol. A maximum
      TPD (TPD(max)) was obtained for each irradiation condition from the relationship
      between the TPD and the thickness of boron dose enhancer (BDE) used. For a mono
      energetic 1.900 MeV proton beam, the deepest TPD(max) of 3.88 cm was attained at
      the (7)Li-target thickness of t(min) and a polyethylene BDE of 1.10 cm. When the
      intended TPD for a BNCT clinical treatment is shallower than the deepest
      TPD(max), the usable (7)Li-target thickness would be between t(min) and an upper
      limit t(upper) whose value depends on the BDE thickness used. In terms of the
      effect of stability of the incident proton energy, Gaussian incident proton
      energies stable to within +/-10 keV of 1.900 MeV were found to be feasible for
      the neutron production via the near-threshold (7)Li(p,n)(7)Be reaction for BNCT
      provided that a suitable BDE is used.

PMID- 17228112
TI  - Precision-controlled elution of a 82Sr/82Rb generator for cardiac perfusion
      imaging with positron emission tomography.
AB  - A rubidium-82 ((82)Rb) elution system is described for use with positron emission
      tomography. Due to the short half-life of (82)Rb (76 s), the system physics must
      be modelled precisely to account for transport delay and the associated activity
      decay and dispersion. Saline flow is switched between a (82)Sr/(82)Rb generator
      and a bypass line to achieve a constant-activity elution of (82)Rb. Pulse width
      modulation (PWM) of a solenoid valve is compared to simple threshold control as a
      means to simulate a proportional valve. A predictive-corrective control (PCC)
      algorithm is developed which produces a constant-activity elution within the
      constraints of long feedback delay and short elution time. The system model
      parameters are adjusted through a self-tuning algorithm to minimize error versus
      the requested time-activity profile. The system is self-calibrating with 2.5%
      repeatability, independent of generator activity and elution flow rate. Accurate
      30 s constant-activity elutions of 10-70% of the total generator activity are
      achieved using both control methods. The combined PWM-PCC method provides
      significant improvement in precision and accuracy of the requested elution
      profiles. The (82)Rb elution system produces accurate and reproducible constant
      activity elution profiles of (82)Rb activity, independent of parent (82)Sr
      activity in the generator. More reproducible elution profiles may improve the
      quality of clinical and research PET perfusion studies using (82)Rb.

PMID- 17228113
TI  - Horizontal shear wave scattering from a nonwelded interface observed by magnetic
      resonance elastography.
AB  - A method based on magnetic resonance elastography is presented that allows
      measuring the weldedness of interfaces between soft tissue layers. The technique
      exploits the dependence of shear wave scattering at elastic interfaces on the
      frequency of vibration. Experiments were performed on gel phantoms including
      differently welded interfaces. Plane wave excitation parallel to the planar
      interface with corresponding motion sensitization enabled the observation of only
      shear-horizontal (SH) wave scattering. Spatio-temporal filtering was applied to
      calculate scattering coefficients from the amplitudes of the incident,
      transmitted and reflected SH-waves in the vicinity of the interface. The results
      illustrate that acoustic wave scattering in soft tissues is largely dependent on
      the connectivity of interfaces, which is potentially interesting for imaging
      tissue mechanics in medicine and biology.

PMID- 17228114
TI  - Evaluation of on-board kV cone beam CT (CBCT)-based dose calculation.
AB  - On-board CBCT images are used to generate patient geometric models to assist
      patient setup. The image data can also, potentially, be used for dose
      reconstruction in combination with the fluence maps from treatment plan. Here we
      evaluate the achievable accuracy in using a kV CBCT for dose calculation.
      Relative electron density as a function of HU was obtained for both planning CT
      (pCT) and CBCT using a Catphan-600 calibration phantom. The CBCT calibration
      stability was monitored weekly for 8 consecutive weeks. A clinical treatment
      planning system was employed for pCT- and CBCT-based dose calculations and
      subsequent comparisons. Phantom and patient studies were carried out. In the
      former study, both Catphan-600 and pelvic phantoms were employed to evaluate the
      dosimetric performance of the full-fan and half-fan scanning modes. To evaluate
      the dosimetric influence of motion artefacts commonly seen in CBCT images, the
      Catphan-600 phantom was scanned with and without cyclic motion using the pCT and
      CBCT scanners. The doses computed based on the four sets of CT images (pCT and
      CBCT with/without motion) were compared quantitatively. The patient studies
      included a lung case and three prostate cases. The lung case was employed to
      further assess the adverse effect of intra-scan organ motion. Unlike the phantom
      study, the pCT of a patient is generally acquired at the time of simulation and
      the anatomy may be different from that of CBCT acquired at the time of treatment
      delivery because of organ deformation. To tackle the problem, we introduced a set
      of modified CBCT images (mCBCT) for each patient, which possesses the geometric
      information of the CBCT but the electronic density distribution mapped from the
      pCT with the help of a BSpline deformable image registration software. In the
      patient study, the dose computed with the mCBCT was used as a surrogate of the
      'ground truth'. We found that the CBCT electron density calibration curve differs
      moderately from that of pCT. No significant fluctuation was observed in the
      calibration over the period of 8 weeks. For the static phantom, the doses
      computed based on pCT and CBCT agreed to within 1%. A notable difference in CBCT-
      and pCT-based dose distributions was found for the motion phantom due to the
      motion artefacts which appeared in the CBCT images (the maximum discrepancy was
      found to be approximately 3.0% in the high dose region). The motion artefacts
      induced dosimetric inaccuracy was also observed in the lung patient study. For
      the prostate cases, the mCBCT- and CBCT-based dose calculations yielded very
      close results (<2%). Coupled with the phantom data, it is concluded that the CBCT
      can be employed directly for dose calculation for a disease site such as the
      prostate, where there is little motion artefact. In the prostate case study, we
      also noted a large discrepancy between the original treatment plan and the CBCT
      (or mCBCT)-based calculation, suggesting the importance of inter-fractional organ
      movement and the need for adaptive therapy to compensate for the anatomical
      changes in the future.

PMID- 17228115
TI  - Influence of Poisson's ratio on elastographic direct and inverse problems.
AB  - We consider the displacement of an elastic material under an external compression
      (axial or almost axial stress). We assume that only one component of the
      displacement is observed, in the direction of compression (axial displacement),
      or alternatively, that two components are observed in a plane. These hypotheses
      are in accordance with an imaging modality, namely ultrasonic elastography. In
      the case of a homogeneous medium we show that any value of Poisson's ratio allows
      us to predict the observed value of the axial displacement. When two components
      of the displacement are measured in a plane, the Poisson's ratio of the plane
      strain model that predicts the observed displacement is not the same as the tri
      dimensional material. These facts are illustrated by numerical experiments in the
      case of an inhomogeneous medium. We also present results on experimental phantom
      data, where the inverse problem of reconstructing the Young's modulus is solved
      assuming different values for Poisson's ratio.

PMID- 17228116
TI  - Nonlinear optical microscopy at wavelengths exceeding 1.4 microm using a
      synchronously pumped femtosecond-pulsed optical parametric oscillator.
AB  - A singly resonant femtosecond-pulsed synchronously pumped optical parametric
      oscillator (SPOPO) is reported that provides a wavelength-tunable alternative to
      the Cr:forsterite source for nonlinear microscopy applications. Periodically
      poled lithium niobate within an external resonator was synchronously pumped by a
      commercial fs-pulsed Nd:YLF laser source to provide fs-pulsed continuously
      tunable radiation from 1.45 to 1.63 microm. Third harmonic generation (THG)
      microscopy and three-photon laser scanning fluorescence microscopy (3PLSM) of a
      range of samples were subsequently performed using this long-wavelength SPOPO
      source. The ability to tune the excitation wavelength delivered to the sample
      significantly improved the efficiency of both the 3PLSM and THG imaging
      experiments.

PMID- 17228117
TI  - Influence of dose engine accuracy on the optimum dose distribution in intensity
      modulated proton therapy treatment plans.
AB  - Analytical dose computation algorithms like pencil beam algorithms (PB) are
      presently used for clinical treatment planning in intensity-modulated proton
      therapy. PB offer fast computation times, but are based on substantial
      approximations. Monte Carlo algorithms (MC) offer better accuracy, but are
      slower. We present a comparison of optimized treatment plans for six patients
      computed either with PB or MC. Both PB and MC are used during optimization, plus
      MC is used to recompute PB results. PB is used with different accuracy settings
      that define the coarseness of approximation. We evaluate the errors of PB
      optimized treatment plans via comparison with MC optimized plans (convergence
      errors) and MC recomputed plans (systematic errors) occurring for different
      accuracy settings of the PB. The level of lateral heterogeneities, being one of
      the main sources of inaccuracies of the PB, is quantified by a formula. In
      geometries with high levels of lateral heterogeneities, the shortcomings of PB
      are most obvious. For these geometries, simple PB lead to clinically significant
      differences and more accurate PB settings have to be used to diminish the error.
      The most accurate PB settings lead however to longer computing times by
      approximately a factor of 2 to 4 compared to PB with simple settings. Although
      the errors can be diminished, they cannot be fully eliminated even with
      sophisticated PB. Further gain in accuracy can therefore only be reached with MC
      in optimization. The use of MC in optimization is technically feasible, the
      computing times are however about 25 to 50 times longer compared to PB with most
      accurate settings.

PMID- 17228118
TI  - Robust fluoroscopic respiratory gating for lung cancer radiotherapy without
      implanted fiducial markers.
AB  - For gated lung cancer radiotherapy, it is difficult to generate accurate gating
      signals due to the large uncertainties when using external surrogates and the
      risk of pneumothorax when using implanted fiducial markers. We have previously
      investigated and demonstrated the feasibility of generating gating signals using
      the correlation scores between the reference template image and the fluoroscopic
      images acquired during the treatment. In this paper, we present an in-depth
      study, aiming at the improvement of robustness of the algorithm and its
      validation using multiple sets of patient data. Three different template
      generating and matching methods have been developed and evaluated: (1) single
      template method, (2) multiple template method, and (3) template clustering
      method. Using the fluoroscopic data acquired during patient setup before each
      fraction of treatment, reference templates are built that represent the tumour
      position and shape in the gating window, which is assumed to be at the end-of
      exhale phase. For the single template method, all the setup images within the
      gating window are averaged to generate a composite template. For the multiple
      template method, each setup image in the gating window is considered as a
      reference template and used to generate an ensemble of correlation scores. All
      the scores are then combined to generate the gating signal. For the template
      clustering method, clustering (grouping of similar objects together) is performed
      to reduce the large number of reference templates into a few representative ones.
      Each of these methods has been evaluated against the reference gating signal as
      manually determined by a radiation oncologist. Five patient datasets were used
      for evaluation. In each case, gated treatments were simulated at both 35% and 50%
      duty cycles. False positive, negative and total error rates were computed.
      Experiments show that the single template method is sensitive to noise; the
      multiple template and clustering methods are more robust to noise due to the
      smoothing effect of aggregation of correlation scores; and the clustering method
      results in the best performance in terms of computational efficiency and
      accuracy.

PMID- 17228119
TI  - Searching for the best model: ambiguity of inverse solutions and application to
      fetal magnetoencephalography.
AB  - Fetal brain signals produce weak magnetic fields at the maternal abdominal
      surface. In the presence of much stronger interference these weak fetal fields
      are often nearly indistinguishable from noise. Our initial objective was to
      validate these weak fetal brain fields by demonstrating that they agree with the
      electromagnetic model of the fetal brain. The fetal brain model is often not
      known and we have attempted to fit the data to not only the brain source
      position, orientation and magnitude, but also to the brain model position.
      Simulation tests of this extended model search on fetal MEG recordings using
      dipole fit and beamformers revealed a region of ambiguity. The region of
      ambiguity consists of a family of models which are not distinguishable in the
      presence of noise, and which exhibit large and comparable SNR when beamformers
      are used. Unlike the uncertainty of a dipole fit with known model plus noise,
      this extended ambiguity region yields nearly identical forward solutions, and is
      only weakly dependent on noise. The ambiguity region is located in a plane
      defined by the source position, orientation, and the true model centre, and will
      have a diameter approximately 0.67 of the modelled fetal head diameter. Existence
      of the ambiguity region allows us to only state that the fetal brain fields do
      not contradict the electromagnetic model; we can associate them with a family of
      models belonging to the ambiguity region, but not with any specific model. In
      addition to providing a level of confidence in the fetal brain signals, the
      ambiguity region knowledge in combination with beamformers allows detection of
      undistorted temporal waveforms with improved signal-to-noise ratio, even though
      the source position cannot be uniquely determined.

PMID- 17228120
TI  - Recovery of total I-131 activity within focal volumes using SPECT and 3D OSEM.
AB  - We experimentally investigated the SPECT recovery of I-131 activity in multiple
      spheres located simultaneously at different locations within a cylindrical
      phantom that had an elliptical cross section. The sphere volumes ranged from 209
      cc down to 4.2 cc. A Prism 3000 camera and two types of parallel-hexagonal-hole
      collimation were employed: high energy (HE) and ultra high energy (UHE). Using
      appropriately-different 3D models of the point source response function for the
      two types of collimation, approximately the same recovery of activity could be
      achieved with either collimation by 3D OSEM reconstruction. The recovery
      coefficient was greater with no background activity in the phantom by 0.10, on
      average, compared to that with background. In the HE collimation case, the
      activity recovery was considerably better for all volumes using 3D OSEM
      reconstruction than it had been in the past using 1D SAGE reconstruction.
      Recovery-coefficient-based correction in a simulated patient case involving
      spherical tumours moderately improved the activity estimates (average error
      reduced from 14% to 9% for UHE collimation, and from 15% to 11% for HE
      collimation). For a test case with HE collimation, increasing the projection
      image sampling density while decreasing the image voxel size increased the
      recovery coefficient by 0.075 on average, and, if used in a full set of
      calibration measurements of recovery coefficient versus volume, might lead to
      further improvement in accuracy for the patient case.

PMID- 17228121
TI  - Improvement of spatial resolution in the longitudinal direction for isotropic
      imaging in helical CT.
AB  - Experiments were conducted to confirm the isotropic spatial resolution of
      multislice CT with a 0.5 mm slice thickness. Isotropic spatial resolution means
      that the spatial resolution in the transaxial plane (X-Y plane) and that in the
      longitudinal direction (Z direction) are equivalent. To obtain point spread
      function (PSF) values in the X-Y-Z directions, three-dimensional voxel data were
      obtained by helical scanning of a bead phantom. The modulation transfer function
      (MTF) values were then obtained by three-dimensional Fourier transform of the
      PSF. Evaluation of the spatial resolution in the X-Y-Z directions by the MTF
      values showed that the spatial resolution in the Z direction does not depend on
      the reconstruction kernel used. It was also found that the spatial resolution in
      the Z direction, as compared with that in the X-Y plane, is superior with the
      standard kernel for the abdomen and is inferior with the high-definition kernel
      for the ears/bones. By performing sharpening filter processing in the Z direction
      with a high-definition kernel, comparable spatial resolution could be obtained in
      the X-Y-Z directions. It was confirmed that adjusting the spatial resolution in
      the Z direction with the reconstruction kernel used is an effective method for
      isotropic imaging.

PMID- 17228122
TI  - In vivo areal modulus of elasticity estimation of the human tympanic membrane
      system: modelling of middle ear mechanical function in normal young and aged
      ears.
AB  - The quasi-static elastic properties of the tympanic membrane system can be
      described by the areal modulus of elasticity determined by a middle ear model.
      The response of the tympanic membrane to quasi-static pressure changes is
      determined by its elastic properties. Several clinical problems are related to
      these, but studies are few and mostly not comparable. The elastic properties of
      membranes can be described by the areal modulus, and these may also be
      susceptible to age-related changes reflected by changes in the areal modulus. The
      areal modulus is determined by the relationship between membrane tension and
      change of the surface area relative to the undeformed surface area. A middle ear
      model determined the tension-strain relationship in vivo based on data from
      experimental pressure-volume deformations of the human tympanic membrane system.
      The areal modulus was determined in both a younger (n = 10) and an older (n = 10)
      group of normal subjects. The areal modulus for lateral and medial displacement
      of the tympanic membrane system was smaller in the older group (mean = 0.686 and
      0.828 kN m(-1), respectively) compared to the younger group (mean = 1.066 and
      1.206 kN m(-1), respectively), though not significantly (2p = 0.10 and 0.11,
      respectively). Based on the model the areal modulus was established describing
      the summated elastic properties of the tympanic membrane system. Future model
      improvements include exact determination of the tympanic membrane area accounting
      for its shape via 3D finite element analyses. In vivo estimates of Young's
      modulus in this study were a factor 2-3 smaller than previously found in vitro.
      No significant age-related differences were found in the elastic properties as
      expressed by the areal modulus.

PMID- 17228123
TI  - A greedy heuristic using adjoint functions for the optimization of seed and
      needle configurations in prostate seed implant.
AB  - We continue our work on the development of an efficient treatment-planning
      algorithm for prostate seed implants by incorporation of an automated seed and
      needle configuration routine. The treatment-planning algorithm is based on region
      of interest (ROI) adjoint functions and a greedy heuristic. As defined in this
      work, the adjoint function of an ROI is the sensitivity of the average dose in
      the ROI to a unit-strength brachytherapy source at any seed position. The greedy
      heuristic uses a ratio of target and critical structure adjoint functions to rank
      seed positions according to their ability to irradiate the target ROI while
      sparing critical structure ROIs. Because seed positions are ranked in advance and
      because the greedy heuristic does not modify previously selected seed positions,
      the greedy heuristic constructs a complete seed configuration quickly. Isodose
      surface constraints determine the search space and the needle constraint limits
      the number of needles. This study additionally includes a methodology that scans
      possible combinations of these constraint values automatically. This automated
      selection scheme saves the user the effort of manually searching constraint
      values. With this method, clinically acceptable treatment plans are obtained in
      less than 2 min. For comparison, the branch-and-bound method used to solve a
      mixed integer-programming model took close to 2.5 h to arrive at a feasible
      solution. Both methods achieved good treatment plans, but the speedup provided by
      the greedy heuristic was a factor of approximately 100. This attribute makes this
      algorithm suitable for intra-operative real-time treatment planning.

PMID- 17228124
TI  - High accuracy multiple scatter modelling for 3D whole body PET.
AB  - A new technique for modelling multiple-order Compton scatter which uses the
      absolute probabilities relating the image space to the projection space in 3D
      whole body PET is presented. The details considered in this work give a valuable
      insight into the scatter problem, particularly for multiple scatter. Such
      modelling is advantageous for large attenuating media where scatter is a dominant
      component of the measured data, and where multiple scatter may dominate the total
      scatter depending on the energy threshold and object size. The model offers
      distinct features setting it apart from previous research: (1) specification of
      the scatter distribution for each voxel based on the transmission data, the
      physics of Compton scattering and the specification of a given PET system; (2)
      independence from the true activity distribution; (3) in principle no scaling or
      iterative process is required to find the distribution; (4) explicit multiple
      scatter modelling; (5) no scatter subtraction or addition to the forward model
      when included in the system matrix used with statistical image reconstruction
      methods; (6) adaptability to many different scatter compensation methods from
      simple and fast to more sophisticated and therefore slower methods; (7) accuracy
      equivalent to that of a Monte Carlo model. The scatter model has been validated
      using Monte Carlo simulation (SimSET).

PMID- 17228125
TI  - Reduced-order parameter optimization for simplifying prostate IMRT planning.
AB  - Intensity-modulated radiotherapy (IMRT) has become an effective tool for cancer
      treatment with radiation. However, even expert radiation planners still need to
      spend a substantial amount of time manually adjusting IMRT optimization
      parameters such as dose limits and costlet weights in order to obtain a
      clinically acceptable plan. In this paper, we describe two main advances that
      simplify the parameter adjustment process for five-field prostate IMRT planning.
      First, we report the results of a sensitivity analysis that quantifies the effect
      of each hand-tunable parameter of the IMRT cost function on each clinical
      objective and the overall quality of the resulting plan. Second, we show that a
      recursive random search over the six most sensitive parameters as an outer loop
      in IMRT planning can quickly and automatically determine parameters for the cost
      function that lead to a plan meeting the clinical requirements. Our experiments
      on a ten-patient dataset show that for 70% of the cases, we can automatically
      determine a plan in 10 min (on the average) that is either clinically acceptable
      or requires only minor adjustment by the planner. The outer-loop optimization can
      be easily integrated into a traditional IMRT planning system.

PMID- 17228126
TI  - Room scatter factor modelling and measurement error analysis of 192Ir HDR
      calibration by a Farmer chamber.
AB  - We introduce an empirical formula to directly calculate the room scatter factor
      in the calibration of (192)Ir HDR using a Farmer chamber. Compared to the data of
      Selvam et al (2001 Phys. Med. Biol. 46 2299), our formula is accurate to within
      0.3%. Our method saves time because the room scatter can be obtained in one
      calculation rather than being deduced through a series of setups of different
      source-chamber distances. It could also be cost effective because a calibration
      jig might be no longer necessary. We only need to position the applicator and
      chamber at a fixed space in air and measure its distance. We also analysed the
      effects of two possible errors arising from ignoring the room scatter and the
      measurement error of the source-chamber distance. We recommend that the source
      chamber distance should be at least 10 cm.

PMID- 17228127
TI  - Current concepts in the treatment of autoimmune pancreatitis.
AB  - Autoimmune pancreatitis is a recently described chronic inflammatory disease of
      the pancreas which appears to be part of a systemic disorder characterized by a
      lymphoplasmacytic infiltrate in affected organs that is rich in IgG4 positive
      cells. The inflammatory component of the disease appears to resolve with steroid
      treatment, though relapses do occur. Here we briefly discuss the role of steroid
      therapy in the management of autoimmune pancreatitis.

PMID- 17228128
TI  - Epidermal growth factor receptor inhibition strategies in pancreatic cancer:
      past, present and the future.
AB  - Pancreatic carcinoma is an unusually lethal disease and to date treatment with
      standard chemotherapy has yielded disappointing results. The epidermal growth
      factor receptor (EGFR) is known to be over-expressed in pancreatic cancer and
      there is data to suggest that this molecular characteristic may be a poor
      prognostic factor as it may denote a more aggressive form of the disease. Current
      therapeutic modalities to target the EGFR include monoclonal antibodies directed
      against the extracellular domain of the receptor as well as tyrosine kinase
      inhibitors that disable the activating portion of the receptor. Preclinical
      studies in pancreatic cancer models have demonstrated the efficacy of both of
      these treatment options and at present they are in various stages of clinical
      testing in combination with other cytotoxic drugs, with other biologic therapies
      and in conjunction with radiotherapy. The combination of gemcitabine and one of
      the tyrosine kinase inhibitors, erlotinib, is the first combination therapy to
      demonstrate survival benefits in pancreatic cancer in a phase III study albeit a
      modest one. Increased understanding of the EGFR pathway may permit the use of
      other targeted agents to either augment therapeutic efficacy or circumvent
      resistance. Additional EGFR targeted strategies for pancreatic cancer are being
      developed that may further circumvent mechanisms resistance to EGFR inhibition.

PMID- 17228129
TI  - Pancreatic cancer incidence in relation to female reproductive factors: Iowa
      Women's Health Study.
AB  - OBJECTIVE: Motivated by inconsistent literature, we evaluated the association
      between incident pancreatic cancer and reproductive characteristics. DESIGN: The
      Iowa Women's Health Study is a large prospective population-based cohort followed
      from 1986 to 2003. Reproductive information was self-reported. PARTICIPANTS: The
      study population comprised 37,459 women aged 55-69 years at baseline. Over 18
      years, 228 incident pancreatic cancers were identified. RESULTS: In a
      multivariate-adjusted model there were no associations between incident
      pancreatic cancer and age at first birth, number of births, age at menarche, or
      use of hormones. There was a statistically significant inverse association
      between age at menopause and pancreatic cancer incidence. Compared to menopause
      less than 45 years, the hazard ratio of pancreatic cancer was 0.61 (95% CI, 0.40
      0.94) for menopause at 45-49 years, 0.75 (95% CI, 0.51-1.09) for 50-54 years, and
      0.35 (95% CI, 0.18-0.68) for menopause at 55 years or more (P trend=0.005). This
      association held after restricting the cohort to never smokers. The associations
      between pancreatic cancer and ages at natural and surgical menopause followed
      similar patterns. In a parallel fashion, risk of pancreatic cancer was decreased
      for women with intact ovaries compared to those who had oophorectomy: hazard
      ratio was 0.70 (95% CI, 0.50-0.99). CONCLUSIONS: Our results indicate that older
      age at menopause is associated with reduced pancreatic cancer risk, but further
      research is warranted.

PMID- 17228130
TI  - Heterotopic pancreas mimicking cholangiocarcinoma. Case report and literature
      review.
AB  - CONTEXT: Majority of the patients developing obstructive jaundice have an
      underlying malignancy. Identification of a benign pathology like heterotopic
      pancreas as an aetiology is uncommon and usually occurs only subsequent to a
      major operation. CASE REPORT: We report a case of heterotopic pancreas adjacent
      to the ampulla of Vater mimicking distal cholangiocarcinoma. A 47-year-old
      patient presented with abdominal pain and obstructive jaundice. ERCP demonstrated
      a distal common bile duct stricture suspicious of cholangiocarcinoma. He
      underwent a pylorus-preserving pancreaticoduodenectomy. Histology showed a nodule
      of heterotopic pancreatic tissue adjacent to the ampulla. CONCLUSION: We have
      reviewed the literature on heterotopic pancreas of the periampullary region
      presenting with biliary obstruction. This is a rare entity and remains difficult
      to diagnose, despite advances in radiological and endoscopic imaging techniques.
      For symptomatic patients with an established diagnosis of periampullary
      heterotopic pancreas, local excision may be sufficient. However, in the absence
      of unequivocal imaging or histological confirmation of benign pathology, and when
      there is a suspicion of underlying malignancy, pancreaticoduodenectomy may be the
      only treatment option, as in this case.

PMID- 17228131
TI  - Diagnosis of a metastatic phyllodes tumor of the pancreas using EUS-FNA.
AB  - CONTEXT: Phyllodes tumors are rare fibro-epithelial lesions which make up less
      than 1% of all breast neoplasms. After curative surgery, distant metastases may
      occur without local recurrence; the typical sites of the metastases being the
      lungs and the bones. Endoscopic ultrasound (EUS) and EUS-guided fine needle
      aspiration (EUS-FNA) has emerged as the leading modalities for the evaluation of
      pancreatic masses. Until now, there have been no published reports on the use of
      EUS-FNA to diagnose recurrent phyllodes tumors metastatic to the pancreas. CASE
      REPORT: A 55-year-old female was hospitalized for the problem of painless
      obstructive jaundice due to a pancreatic head mass causing biliary obstruction.
      She had a past history of a left breast phyllodes tumor treated with mastectomy.
      The diagnostic dilemma was whether this was a case of primary pancreatic cancer
      or a recurrent phyllodes tumor presenting as a pancreatic metastasis. EUS-FNA of
      the mass was performed and it revealed a metastatic phyllodes tumor. The patient
      was treated with palliative biliary stenting and was referred for palliative
      chemotherapy. CONCLUSION: This is the first report of a recurrent phyllodes tumor
      metastatic to the pancreas diagnosed using EUS-FNA. It highlights the utility of
      EUS-FNA in characterizing the nature of pancreatic head masses.

PMID- 17228132
TI  - Acute drug induced hepatitis due to erlotinib.
AB  - CONTEXT: Acute drug induced hepatitis has not been commonly associated with
      epidermal growth factor receptor (EGFR) inhibitors. Hepatotoxicity seen with
      erlotinib, a small molecule tyrosine kinase inhibitor to EGFR, is usually
      transient with mild elevation of transaminases. CASE REPORT: We report a case of
      acute severe hepatitis resulting from erlotinib monotherapy in a patient with
      locally advanced pancreatic cancer. Hepatotoxicity resolved once erlotinib was
      discontinued and serum transaminases returned to baseline normal values.
      CONCLUSIONS: Acute severe hepatitis though rare is occasionally observed with
      EGFR inhibitors gefitinib or erlotinib. As EGFR inhibitors are now incorporated
      with chemotherapy in advanced pancreatic cancers, clinicians should be aware of
      this potential complication.

PMID- 17228133
TI  - Follicular lymphoma of the pancreas: a case report and proposed new strategies
      for diagnosis and surgery of benign or low-grade malignant lesions of the head of
      the pancreas.
AB  - CONTEXT: Primary pancreatic lymphoma is a rare form of extranodal lymphoma
      originating in the pancreas. The present report describes a case of follicular
      lymphoma of the pancreas with unique CT and MRI findings. CASE REPORT: A 58-year
      old male complained of sudden abdominal pain, and routine ultrasonography
      detected an 8 cm hypoechoic tumor in the head of the pancreas. The 3D image
      generated using multi-cholangiography and virtual duodenography provided the
      information necessary for a laparotomy. The tumor was enucleated for diagnosis.
      Follicular lymphoma is quite rare in the pancreas and gastrointestinal tract. A
      considerable number of pancreatic lymphoma subtypes have been reported. The
      expression "pancreatic lymphoma" has been used to describe both primary lymphoid
      neoplasms originating in the pancreatic parenchyma and tumors invading from a
      peri-pancreatic lymphadenopathy. The present case belongs to the latter, which
      might explain the unique imaging findings and histological type. These subtypes
      display different imaging findings and different clinical characteristics. In the
      future, primary pancreatic lymphoma should be discussed separately depending on
      the subtype. CONCLUSION: We propose a new subtype of primary pancreatic lymphoma.
      Multi-cholangiography and virtual duodenography provided the information
      necessary for a laparotomy in the present case. Enucleation is indicated for
      benign and low-grade malignant tumors of the pancreas, even if the tumor is
      located in the head of the pancreas.

PMID- 17228134
TI  - Ampullary carcinoma associated with an annular pancreas.
AB  - CONTEXT: Annular pancreas is an uncommon congenital abnormality. Co-existence of
      this condition with a pancreaticobiliary malignancy is an exceptionally rare
      occurrence. CASE REPORT: We present a case report of a 78-year-old woman with
      jaundice due to an ampullary carcinoma associated with an annular pancreas
      treated by pancreaticoduodenectomy. CONCLUSIONS: A collection of previously
      reported cases is reviewed together with the relevant literature. Obstructive
      jaundice is an uncommon feature of annular pancreas; hence the possibility of co
      existent pancreaticobiliary malignancy should be excluded.

PMID- 17228135
TI  - Pancreatoblastoma.
AB  - Pancreatoblastoma (PB), or infantile pancreatic carcinoma, is an extremely rare
      pancreatic tumor in childhood, comprising 0.5% of pancreatic non-endocrine
      tumors. Although PB mainly presents during childhood but can also occur in
      adults. PB tend to be less aggressive in infants and children compared to adults.
      Children with PB usually present late with upper abdominal pain and many have a
      palpable mass in the epigastrium. Mechanical obstruction of the upper duodenum
      and gastric outlet by tumor in the head of the pancreas may be associated with
      vomiting, jaundice and gastrointestinal bleeding. Histologically, PB is
      characterized with distinct acinar and squamoid cell differentiation. PB has been
      associated with alterations in the Wnt signaling pathway and chromosome 11p loss
      of heterozygosity (LOH), Beckwith-Wiedemann syndrome and familial adenomatous
      polyposis. The majority of these tumors arise in the head of the pancreas. Alpha
      fetoprotein may be elevated in up to 68% of patients with PB. Ultrasound and CT
      scan may be useful but preoperative diagnosis is often quite difficult. The
      treatment of choice is complete resection, that may often be curative. The role
      of adjuvant chemotherapy or radiotherapy is still under discussion due to small
      number of patients treated as yet. Chemotherapy regimens consisting of
      cyclophosphamide, etoposide, doxorubicin, and cisplatin have been used in
      neoadjuvant setting with anecdotal benefit. Prognosis of this rare tumor is good,
      when resected completely. Prognosis is poorer, when there is metastasis or when
      it is inoperable. On the whole, PB is regarded to be a curable tumor; hence the
      clinical diagnosis should be made early. Awareness of this rare tumor of pancreas
      is essential for early detection and proper management. The author review the
      clinical presentation, etiology, diagnosis, treatment and prognosis of PB in this
      presentation.

PMID- 17228136
TI  - Familial pancreatic cancer: hope can become truth.

PMID- 17228137
TI  - Proceedings of the 30th National Congress of the Italian Association for the
      Study of the Pancreas (AISP). Milan, Italy, September 21-23, 2006.

PMID- 17228138
TI  - Contrast-enhanced ultrasonography of the pancreas.

PMID- 17228139
TI  - The imaging of pancreatic exocrine solid tumors: the role of computed tomography
      and positron emission tomography.
AB  - The only potentially radical treatment for pancreatic cancer is the removal of
      the tumor which can be performed by total or subtotal surgical resection of the
      pancreas; this is possible in the early stages of the disease when the tumor is
      confined to the pancreatic gland without metastasis to the liver, lymph nodes
      and/or the peritoneum, or involvement of the vascular system such as the celiac
      trunk and its branches and the superior mesenteric artery. In this paper, we
      describe the accuracy of computed tomography and positron emission tomography in
      the diagnosis of exocrine pancreatic cancer.

PMID- 17228140
TI  - Pancreatic cancer imaging: the new role of endoscopic ultrasound.
AB  - Pancreatic cancer is the most deadly of all gastrointestinal malignancies and has
      a very poor prognosis. Unfortunately, most patients present late in the course of
      their disease and, at the time of diagnosis, only 10 to 25% of patients will be
      eligible for potentially curative resection. Efforts must be oriented towards an
      early diagnosis and towards reliably identifying patients who can really benefit
      from major surgery. A suspected pancreatic tumor can be a difficult challenge for
      the clinician. In the last ten years, we have witnessed notable technological
      improvements in radiological and nuclear imaging. Taking this into account, we
      will try to delineate the new role of endoscopic ultrasound (EUS) in pancreatic
      tumor imaging and to place EUS in a shareable diagnostic and staging algorithm.
      To date, the most accurate imaging techniques for pancreatic neoplasms remain
      contrast-enhanced computed tomography and EUS. EUS has the highest accuracy in
      detecting small lesions, in assessing tumor size and lymph node involvement, but
      helical CT must still be the first choice in patients with a suspected pancreatic
      tumor. However, after this first step, there is a place for EUS as a second
      diagnostic level in several cases: negative results on CT scan and persistent
      strong clinical suspicion of pancreatic cancer, doubtful results on CT scans or
      the need for cytohistological confirmation. In the near future, there will be
      great opportunities for the development of diagnostic and therapeutic EUS and
      pancreatic cancer could be the best testing ground.

PMID- 17228141
TI  - New therapies for pancreatic cancer: current standard.

PMID- 17228142
TI  - Vascular complications of pancreatectomy.
AB  - Despite decreased postoperative mortality, pancreatic resections continue to be
      associated with high morbidity rates. Vascular complications and, in particular,
      erosive bleeding from the large retroperitoneal vasculature are particularly
      difficult to treat and account for a large percentage of the residual
      postoperative mortality of pancreatic resections. We herein analyze the
      pathogenesis, diagnosis, preventive measures and possible remedies of either
      hemorrhagic or occlusive complications of pancreatic resections through a review
      of the literature and of our institutional experience consisting of 818
      pancreatectomies.

PMID- 17228143
TI  - Medical complications of pancreatic resections.
AB  - The sequelae of pancreas surgery are determined by the type of procedure, the
      extent of the parenchymal resection and the underlying disorder. In ductal
      carcinoma, the outcome is heavily influenced by the disease itself. Mortality
      rates are lower in centers which perform the most operations. In chronic
      pancreatitis, surgical management is essentially therapeutic for complications
      and palliative for the disease whose progress is closely correlated with the
      sequelae. Elective surgery does not appear to increase the risk of diabetes
      whereas distal pancreatectomy is an independent risk factor. Parenchymal
      resection aggravates nutritional deficiencies, such as low selenium, linoleic
      acid, LDL and apolipoprotein B levels, and thus increases the risk of
      atherogenesis. Abstinence from alcohol is an indispensable step towards the
      disappearance of postoperative pain.

PMID- 17228144
TI  - Pancreatectomy for pancreatic disease and quality of life.
AB  - The aim of this paper was to review the data existing in the English literature
      on the quality of life in patients who undergo surgical resection of the
      pancreatic gland either for benign or for malignant diseases. MEDLINE, Web of
      Science, and ScienceDirect were browsed in order to select the data existing in
      the literature on quality of life and pancreatic surgery. Alerts received by e
      mail were also taken into account. Only full text papers were selected. Of the
      161 papers found, only 13 papers were evaluated for the purpose of this study: 11
      focused on surgical resective procedures in chronic pancreatitis and two focused
      their interest on assessing the quality of life related to resective procedures
      in pancreatic neoplasms. Despite the scarcity of studies assessing the quality of
      life in patients who underwent pancreatic surgery, there is the need to routinely
      assess well-being in patients who have been operated on.

PMID- 17228145
TI  - The determinant factors of recurrence following resection for ductal pancreatic
      cancer.
AB  - Long-term survival for patients with pancreatic carcinoma is low, even following
      resection. Most patients who undergo curative treatment, develop recurrence
      usually at the same site of resection or in the liver. Failure seals the fate of
      the patient. Local recurrence occurs frequently; however, it is rarely a direct
      cause of death. In fact, most patients die from distant metastases. From a
      clinical point of view, it is important to distinguish recurrence from relapse.
      In fact, recurrence can be recognized as the reappearance of the disease in the
      surgical bed, often due to inadequate surgical clearance. On the other hand, the
      concept of relapse should be much more related to the appearance of the disease
      in a distant site. Both underestimated staging of the diagnosis and the
      biological features of the tumor can cause relapse. Up to now, there have only
      been a few reviews on the incidence and pattern of failure following resection.
      Detailed knowledge of the recurring sites of pancreatic carcinoma and study of
      the factors influencing disease-free survival are significant in developing
      neoadjuvant, surgical and adjuvant treatment. The aim of this review is to point
      out the major factors most commonly identified as determinants of both recurrence
      and relapse.

PMID- 17228146
TI  - Endoscopic stenting in benign pancreatic diseases.
AB  - The role of endoscopic therapy in the management of pancreatic diseases is
      continuously evolving; at present, most pathological conditions of the pancreas
      are successfully treated by endoscopic retrograde cholangiopancreatography
      (ERCP), endoscopic ultrasound (EUS) or both. Endoscopic placement of stents has
      played and still plays a major role in the treatment of chronic pancreatitis,
      pseudocysts, pancreas divisum, main pancreatic duct injuries, pancreatic
      fistulae, complications of acute pancreatitis, recurrent idiopathic pancreatitis
      and in the prevention of post-ERCP pancreatitis. These stents are currently
      routinely placed to reduce intraductal hypertension, bypass obstructing stones,
      restore lumen patency in cases with dominant, symptomatic strictures, seal main
      pancreatic duct disruption, drain pseudocysts or fluid collections, treat
      symptomatic major or minor papilla sphincter stenosis, and prevent procedure
      induced acute pancreatitis. The present review aims at updating and discussing
      techniques, indications and results of endoscopic pancreatic duct stent placement
      in acute and chronic inflammatory diseases of the pancreas.

PMID- 17228147
TI  - Giant calcified bulla compressing the mediastinum.

PMID- 17228148
TI  - Duodenal cancer diagnosed by capsule endoscopy and double balloon enteroscopy in
      a patient with hereditary nonpolyposis colorectal cancer.

PMID- 17228149
TI  - Celecoxib and curcumin additively inhibit the growth of colorectal cancer in a
      rat model.
AB  - BACKGROUND: Multiple studies have indicated that specific COX-2 inhibitors may
      prevent CRC. However, the long-term use of COX-2 inhibitors is not toxicity-free
      and may be limited due to its cardiovascular side effects. The present study was
      carried out to examine the chemopreventive effects of celecoxib and curcumin
      alone and in combination using the 1,2-dimethylhydrazine (DMH) rat model.
      METHODS: Male rats were injected with DMH and randomly divided into four groups
      that consumed one of the following diets: (a) AIN-076 control diet; (b) AIN
      076/curcumin (0.6%); (c) AIN-076/celecoxib (0.16%), or (d) AIN-076/celecoxib
      (0.16%) and curcumin (0.6%). Aberrant crypt foci (ACF) were identified by
      intensive staining with methylene blue in comparison to the surrounding normal
      crypts. RESULTS: The average number of ACF per rat colon was 64.2 +/- 3 in the
      control group, 39 +/- 5 and 47 +/- 10 for the curcumin- and celecoxib-treated
      group, respectively, and 24.5 +/- 6 in the group that had received both agents.
      CONCLUSIONS: In vivo, curcumin augments the growth inhibitory effect of
      celecoxib. This may be clinically important as this dose of celecoxib can be
      achieved in human serum following standard anti-inflammatory dosing of 100 mg.

PMID- 17228150
TI  - The changes in angiogenic gene expression in recurrent multiple chorioangiomas.
AB  - OBJECTIVES: To assess the messenger ribonucleic acid expression in placental
      tissue of growth factors, cytokines, angiogenic and anti-angiogenic factors in
      one case of recurrent multiple chorioangiomas. METHODS: Complementary
      deoxyribonucleic acid array analysis was performed on the affected placentae and
      on normal placentaes (controls) to compare messenger ribonucleic acid levels of
      96 genes involved in angiogenesis. RESULTS: Eleven genes presented more than two
      fold alteration in expression levels: undetectable (angiopoietin 1, osteonectin,
      tyrosine kinase endothelial, neuropilin 1), decreased (transcription growth
      factor beta receptor 3, tissue inhibitor of metalloproteinase type 2, EGF
      receptor, integrin-alpha V, tyrosine kinase vascular endothelial growth factor
      receptor 2), increased (angiopoietin 2, osteopontin). CONCLUSIONS: We illustrated
      the complexity of angiogenic disruption in recurrent multiple chorioangiomas
      leading to the difficulty to propose a single candidate gene to explain this
      pathology.

PMID- 17228151
TI  - Intrathoracic pressure in congenital chylothorax: keystone for the rationale of
      thoracoamniotic shunting?
AB  - Thoracoamniotic shunting in fetal pleural effusion has poor results, with an
      overall survival of less than 50% when hydrops is associated. Those cases without
      hydrops presented the best evolution, but the indication in these cases remains
      controversial. We present a dichorionic diamniotic twin pregnancy at 29 weeks'
      with right pleural effusion and hydrops, in which one fetus presented diaphragm
      inversion and mediastinal shift, both considered as ultrasonographic signs of
      thoracic hypertension. A thoracoamniotic shunt reversed these signs immediately.
      Nevertheless, 1 week after, these signs and skin edema reappeared and the
      effusion increased, leading to a second thoracocenthesis for drainage and
      intrathoracic pressure measurement. Amniotic fluid and intrathoracic pressures
      were found at 21 and 39 mm Hg, respectively. A cesarean section was performed and
      the catheter was found to be obliterated by cellular detritus of leukocytes and
      fibrin. Our conclusion is that ultrasonographic signs of elevated thoracic
      pressure are a keystone for the shunt indication, and that this could be
      corroborated by direct measurements. This can be an important parameter for
      precise indication of thoracoamniotic shunting.

PMID- 17228152
TI  - Prenatal sonographic diagnosis of a rare Cantrell's pentalogy variant with
      associated open neural tube defect - a case report.
AB  - Cantrell's pentalogy is a very rare congenital anomaly. The hallmark of this
      condition is the presence of ectopia cordis and an abdominal wall defect. Its
      association with craniorachischisis is even more infrequent with just a few cases
      reported in the literature. The authors describe a case of a prenatal ultrasound
      diagnosis of Cantrell's pentalogy with posterior encephalocele and spinal
      dysraphism associated.

PMID- 17228153
TI  - Use of T-cell antibodies for donor dosaging in a canine model of in utero
      hematopoietic stem cell transplantation.
AB  - AIM: Microchimerism following canine in utero hematopoietic stem cell
      transplantation (IUHSCT) development of T-cell dosing regimens. OBJECTIVE: To
      investigate the use of anti-T-cell antibodies for cell dosing of the donor graft
      in a canine model of IUHSCT. STUDY DESIGN: Canine IUHSCT was performed by
      ultrasound-guided intraperitoneal injection in days 35-38 of fetal canines with
      CD34(+) cells at doses of 4.5 x 10(8) to 1.3 x 10(9) cells/kg and T cells (CD3(+)
      CD5(+)) at doses of 8 x 10(6) to 8.8 x 10(8) cells/kg. Postnatal studies included
      tissue histology and polymerase chain reaction-based chimerism analysis. RESULTS:
      Term survival was 86-100%. Microchimerism (0-2%) was detected in five of eight
      recipients in multiple tissues. Histopathology revealed no evidence of graft
      versus-host disease (GVHD). CONCLUSION: Canine IUHSCT is a useful model to
      investigate the role of donor T cells in engraftment and GVHD. IUHSCT at early
      gestational ages with high doses of donor T cells in the graft yields
      microchimerism in multiple tissues without GVHD.

PMID- 17228154
TI  - Transient chorioamniotic membrane separation after fetoscope guide laser therapy
      for twin-twin transfusion syndrome: a case report.
AB  - Chorioamniotic membrane separation (CMS) means that the close attachment of
      amniotic and chorionic membranes is disrupted, usually following the traumatic
      entry into the amniotic cavity including fetal therapy. We report a case of twin
      twin transfusion syndrome receiving fetoscopic guide laser therapy at gestational
      age of 19 weeks with partial CMS detected at the fifth week (gestational age of
      24 weeks) after surgery and resealed 1 week later. There was no more CMS noted
      till delivery at gestational age of 34 weeks 6 days. CMS after fetoscope surgery
      may reseal spontaneously.

PMID- 17228155
TI  - Diffuse placental chorioangiomatosis and fetal hydrops.
AB  - A highly unusual case of a pregnancy complicated by diffuse placental
      chorioangiomatosis that resulted in a live-birth and short-term fetal survival is
      reported. The potential for antenatal diagnosis and intrauterine treatment to
      optimise fetal outcome is discussed.

PMID- 17228156
TI  - Acute recurrent polyhydramnios: a combination of amniocenteses and NSAID may be
      curative rather than palliative.
AB  - Acute recurrent polyhydramnios is a rare occurrence characterized by a poor fetal
      outcome. This is a case report describing a 34-year-old woman presenting with
      acute recurrent polyhydramnios. Treatment with non-steroidal anti-inflammatory
      drugs (NSAID) and therapeutic amniocenteses was initiated immediately and
      resulted in a decreased amniotic fluid production from 30 weeks' gestation. Even
      after the discontinuation of NSAID treatment, the amniotic fluid production
      normalized, and the woman delivered a healthy boy at 39 weeks 2 days' gestation.
      Amniotic prolactin was measured at three occasions using an enzyme-linked
      immunosorbent assay. As in normal pregnancies, amniotic prolactin levels
      decreased by 80% from highest to lowest value in this case of resolving acute
      recurrent polyhydramnios.

PMID- 17228157
TI  - Fetoscopic laser surgery in 100 pregnancies with severe twin-to-twin transfusion
      syndrome in the Netherlands.
AB  - OBJECTIVE: In this prospective cohort study, we evaluated the initial results of
      fetoscopic laser surgery for severe second trimester twin-to-twin transfusion
      syndrome (TTTS) treated at our centre. METHOD: A total of 100 consecutive
      pregnancies with severe second trimester TTTS treated at our centre with
      selective fetoscopic laser coagulation of vascular anastomoses on the placental
      surface between August 2000 and November 2004 were included in the study.
      Perinatal survival was analysed in relation to Quintero stage. RESULTS: Median
      gestational age was 20 weeks at fetoscopy (range: 16-26) and 33 weeks at delivery
      (range: 18-40). Perinatal survival rate was 70% (139/200). The treatment resulted
      in at least one survivor at the age of 4 weeks in 81% of pregnancies. Perinatal
      survival was significantly higher when treatment was performed in the early
      Quintero stages (95% in stage 1, 76% in stage 2, 70% in stage 3, 50% in stage 4)
      (p = 0.02). CONCLUSION: Results of fetoscopic laser surgery for TTTS in our
      centre are similar to those in specialised centres in other countries. Diagnosis
      and treatment in the early Quintero stages resulted in significantly higher
      perinatal survival.

PMID- 17228158
TI  - Fetus-in-fetu: a rare entity.
AB  - Fetus-in-fetu is a malformed parasitic monozygotic diamniotic twin that is found
      inside the body of the living child or adult. A 3-year-old male child presented
      with a retroperitoneal mass, which on radiological examination showed
      retroperitoneal teratoma. Pathological examination revealed fetus-in-fetu with
      partially developed vertebral column.

PMID- 17228159
TI  - Short femurs detected at 25 and 31 weeks of gestation diagnosed as Leroy I-cell
      disease in the postnatal period: a report of two cases.
AB  - Leroy I-cell disease is a rare autosomal recessive lysosomal storage disorder
      characterized by marked psychomotor and growth retardation, skeletal anomalies,
      and typical facial features. There is a biochemical defect in uridine diphospho-N
      acetylglucosamine-1-phosphotransferase, which is the enzyme responsible for
      addition of a mannose phosphate residue for lysosomal trafficking. Prenatal
      diagnosis is possible by analysis of enzyme activity in chorionic villi or
      cultured amniocytes, but this is offered to families only known to be at
      increased risk. We describe two cases that had bilateral shortness of the femurs
      at 25 and 31 weeks of gestation in the ultrasound scan and were diagnosed as
      Leroy I-cell disease by plasma enzyme analysis in the postnatal period. There was
      also bowing of the femurs in one case. None of the two families had a history of
      Leroy I-cell disease. The parents of one case were second-degree cousins. In view
      of these two cases that are presented, we propose that Leroy I-cell disease
      should be included in the differential diagnosis of short femurs even when there
      is no evident family history.

PMID- 17228160
TI  - Alcohol injection for the intrauterine treatment of chorioangioma in a pregnancy
      with transfusion resistant fetal anemia: a case report.
AB  - Chorioangiomas are usually small, clinically inevident, benign vascular lesions
      of the placenta, but larger ones may cause serious perinatal and neonatal
      complications. There is need for in utero intervention in these fetuses. Several
      interventions are described to relieve pathophysiologic insult on fetus. Alcohol
      injection is one of the therapeutic interventions. In this case, we present a
      patient with chorioangioma and early onset of hydrops fetalis and polyhydramnios
      at 24th week of gestation. Successful intratumoral injection of absolute ethyl
      alcohol relieved hydrops fetalis and polyhydramnios. Unfortunately, pregnancy
      ended at 28th week and a 1,330 g fetus was delivered.

PMID- 17228161
TI  - Prenatal diagnosis of Bartter syndrome with biochemical examination of amniotic
      fluid: case report.
AB  - Antenatal Bartter syndrome typically presents with marked fetal polyuria that
      leads to polyhydramnios and premature delivery. In our case, polyhydramnios was
      detected at 26 weeks of gestation and amniotic fluid chloride level was high.
      Serial amnion-drains were performed. During indomethacine treatment, fetal
      bradycardia developed. The mother was given daily oral potassium to maintain
      normal serum level and prevent fetal arrhythmias. After birth, hypokalaemic
      alkalosis, low chloride, hyper-reninemia and hyperaldosteronemia were detected.

PMID- 17228162
TI  - Fulminant sepsis after second-trimester amniocentesis in pregnant women by in
      vitro fertilization and embryo transfer.
AB  - Second-trimester amniocentesis is a common procedure for prenatal diagnosis.
      Sepsis is a rare complication after amniocentesis and may rapidly deteriorate if
      prompt treatment, including broad-spectrum antibiotics and removal of the
      infected abortus, is delayed. In vitro fertilization and embryo transfer (IVF-ET)
      is a standard final treatment for infertile women. Transvaginal oocyte retrieval
      is necessary for such women; this procedure potentially causes Escherichia coli
      attaching and effacing in the abdominal cavity. Here we report that two pregnant
      women by IVF-ET developed sepsis after second-trimester amniocentesis. The cause
      of sepsis after amniocentesis is still unknown. We provided the possibility of
      the causation of the E. coli infection associated with the previous intra
      abdominal procedure, but it needs more evidence to prove it.

PMID- 17228164
TI  - Maternal morbidity following routine second trimester genetic amniocentesis.
AB  - Two cases of septic complications of routine second trimester amniocentesis are
      presented. The first case is a 37-year-old gravida suffering from ulcerative
      colitis who was admitted for amniocentesis in the 18th week of her third
      pregnancy. An uncomplicated transabdominal amniocentesis was performed using a
      sterile technique and ultrasound guidance. Twenty-eight hours later the patient
      had a septic abortion and sepsis. The second case is a 34-year-old gravida in the
      24th week of her pregnancy who was admitted with amnionitis 10 h after an
      uncomplicated amniocentesis, and subsequently had a septic abortion. A high index
      of suspicion and rapid intervention were crucial in both cases.

PMID- 17228163
TI  - Amniocentesis for twin pregnancies: is alpha-fetoprotein useful in confirming
      that the two sacs were sampled?
AB  - OBJECTIVE: To assess if amniotic fluid alpha-fetoprotein (AFAFP) could be useful
      to determine if both sacs are sampled during an amniocentesis for twin
      pregnancies. METHOD: We reviewed all amniocenteses performed on twin pregnancies
      over a 5-year period. Inclusion criteria were restricted to pregnancies where
      both karyotypes and AFAFP were available on each fetus. Pregnancies complicated
      by fetal anomalies were excluded. The following information was obtained:
      maternal age, gestational age at the procedure, karyotypes, AFAFP values,
      pregnancy and neonatal outcome. Placental pathology reports were used to confirm
      chorionicity. Analysis was performed to evaluate the impact of the fetal gender
      and chorionicity on the AFAFP values. RESULTS: 260 pregnancies were reviewed.
      Mean maternal age was 36.9 years (33.6, 40.1). Gestational age at the time of the
      procedure was 16.2 weeks (14.5, 17.9). Complications included 1.8% of
      misdiagnosis (discrepancy between karyotype and gender). The difference of AFAFP
      values between the two fetuses was statistically larger in dichorionic
      pregnancies than in monochorionic gestations. Fetal gender had no influence on
      the AFAFP. CONCLUSION: Amniocentesis in twin pregnancies is associated with a
      1.8% risk of misdiagnosis. AFAFP can help to assess the chorionicity of a twin
      pregnancy. When the difference between the two values is <0.2 MoM and the
      chorionicity was thought to be dichorionic and the two karyotypes are similar,
      then failure to sample both sacs should be suspected.

PMID- 17228165
TI  - Prenatal diagnosis of a fetus with partial trisomy 7p.
AB  - We report a prenatal diagnosis of a fetus with partial trisomy 7p.
      Ultrasonography at 28 weeks of gestation of a 27-year-old multigravid woman
      revealed a growth-retarded fetus with agenesis of the corpus callosum, enlarged
      left kidney, single umbilical artery, hypertelorism, depressed nasal bridge,
      frontal bossing, irregular maxiller alveolar composition, club feet, flexion
      deformity of the upper extremities and Epstein anomaly. Fetal karyotype was
      46,XX,der(9)add(9p24),16qh+. Our results indicated that the fetus had an
      unbalanced translocation, which resulted in duplication of the proximal segment
      of 7p. Maternal karyotype was (46,XX,t(7,9)(p15.3,p24),16qh+). Because fetal
      death occurred at 31 weeks of gestation, induction of labor was performed. An
      enlarged anterior fontanel and micrognathia were seen during fetal autopsy.
      Trisomy 7p is related to a well-known clinical picture with a dismal prognosis.
      Our report showed that the outcome of the affected pregnancy may also be poor.
      Detection of fetal chromosomal abnormality and parental translocations are
      essential for counseling of the parents.

PMID- 17228166
TI  - Etoricoxib tolerability in patients with hypersensitivity to nonsteroidal anti
      inflammatory drugs.
AB  - BACKGROUND: Adverse reactions to nonsteroidal anti-inflammatory drugs (NSAIDs)
      are commonly observed, particularly among patients with chronic urticaria or
      asthma. The identification of a safe and reliable alternative is a frequent
      problem in clinical practice. Our aim was to investigate the clinical
      tolerability of etoricoxib, a new selective cyclooxygenase-2 inhibitor, in a
      group of patients with well-established NSAID hypersensitivity. METHODS: We
      assessed 31 adults (21 women and 10 men) who reported one or more adverse
      reactions to NSAIDs, manifested as cutaneous, respiratory or anaphylactic
      symptoms. Sixteen of them reported reactions to a single NSAID (single reactors)
      and 15 to more than one NSAID (multiple reactors); the most frequently involved
      drug was acetylsalicylic acid. First, each patient underwent allergologic tests
      (skin and/or oral challenge tests) with culprit NSAIDs and then tolerability
      tests with increasing doses of etoricoxib up to 120 mg. All challenges were
      performed under single-blind, placebo-controlled conditions. RESULTS: NSAID
      hypersensitivity was diagnosed in all 31 patients: 3 displayed positive results
      to pyrazolone skin tests and the other 28 to challenges with culprit NSAIDs. None
      reacted to either placebos or etoricoxib. CONCLUSIONS: Etoricoxib seems to be a
      safe alternative for patients with well-demonstrated NSAID hypersensitivity.

PMID- 17228167
TI  - Interleukin-16 inhibits immunoglobulin e production by B lymphocytes.
AB  - BACKGROUND: The increased production of IgE is a hallmark of atopic disorders.
      CD4+ T cells regulate the production of Immunoglobulin (Ig) E by B cells.
      Interleukin (IL) 16, a CD4+ specific cytokine, is highly expressed at sites of
      allergic inflammation. Our aim was to determine the effect of IL-16 on IgE
      production in atopic subjects. METHODS: Freshly isolated peripheral blood
      mononuclear cells (PBMC) from atopic subjects were stimulated with recombinant IL
      (rIL) 4 and anti-CD40 antibody to promote IgE production in the presence or
      absence of rIL-16 added at different time intervals prior to stimulation. The
      levels of IgE in cell culture supernatants collected at day 14 were measured by
      ELISA. The effect of IL-16 on the expression of the Cepsilon transcript was
      evaluated by reverse-transcription polymerase chain reaction. To evaluate whether
      the modulatory effect of IL-16 on IgE production was mediated by interferon-gamma
      (IFN-gamma), anti-CD40/IL-4-stimulated PBMC were cultured in the presence of rIL
      16 and neutralizing concentrations of anti-IFN-gamma antibody. RESULTS: PBMC
      stimulated with rIL-4 (400 U/ml) and anti-CD40 monoclonal antibody (0.5
      microg/ml) produced significant amounts of IgE (range: 1.3-46.0 ng/ml). The
      addition of rIL-16 twenty-four hours before stimulation significantly reduced the
      levels of IgE released by anti-CD40/IL-4-stimulated PBMC (0.5-29.6 ng/ml, p <
      0.05). IL-16 reduced the expression of the Cepsilon transcript in stimulated
      PBMC. IL-16 induced the expression of IFN-gamma mRNA. However, the use of anti
      IFN-gamma antibody did not alter the effect of IL-16 on IgE production. Rescue
      doses of IL-13 did not restore the production of IgE by PBMC treated with IL-16.
      IL-16 did not alter IgE production in CD14-depleted cell preparations suggesting
      that the IL-16-mediated effects on IgE production may be related to CD14+ cells.
      CONCLUSION: These data show that IL-16 inhibits IgE production and therefore may
      play an important regulatory role in atopic disorders.

PMID- 17228168
TI  - Role of human leucocyte antigen DQ in the presentation of T cell epitopes in the
      major cow's milk allergen alphas1-casein.
AB  - BACKGROUND: Little is known about the association between human leucocyte antigen
      (HLA) and cow's milk allergy (CMA). The aim of the present study was to determine
      the HLA restriction of T cell clones (TCCs) specific to alphas1-casein, the most
      abundant milk protein, and to study possible HLA class II allele associations
      with CMA. METHODS: alphas1-Casein-specific TCCs were derived from 6 children with
      CMA, 9 atopic children without CMA and 5 non-atopic children. T cell epitope
      specificity was defined by stimulation with overlapping peptides, spanning the
      alphas1-casein molecule. HLA restriction was determined in proliferation assays
      using antibodies blocking either HLA-DP, HLA-DQ or HLA-DR. HLA genotyping was
      performed in 32 subjects with CMA, 23 atopic and 22 non-atopic individuals.
      RESULTS: Ten TCCs were restricted to HLA-DQ, 6 TCCs to HLA-DR and 4 TCCs to HLA
      DP. The sequence in alphas1-casein that was most immunogenic to T cells from
      children with CMA contained T cell epitopes restricted to DQB1*0201, DPB1*0401
      and DRB1*1501. The DQB1*0501 allele frequency was lower in children with CMA than
      in non-atopic children, but this difference could not be confirmed in an
      additional group of subjects with and without CMA. CONCLUSIONS: HLA-DQ plays a
      substantial role in the presentation of T cell epitopes in alphas1-casein.
      However, HLA class II allele frequencies do not show major differences between
      cow's milk allergic, atopic and non-atopic subjects. T cell epitopes in the most
      immunogenic region are presented by various abundantly present HLA genotypes.
      Therefore, this sequence may be a suitable target for peptide immunotherapy.

PMID- 17228169
TI  - Immunotherapy with an aluminum hydroxide-adsorbed Juniperus ashei foreign pollen
      extract in seasonal indigenous cypress pollen rhinoconjunctivitis. A double
      blind, placebo-controlled study.
AB  - BACKGROUND: The efficacy of standardized Juniperus ashei extract was assessed in
      patients with allergic rhinoconjunctivitis due to European cypress pollens.
      METHODS: Forty adults with European cypress-allergic rhinoconjunctivitis were
      randomized to receive immunotherapy or a matched placebo. Specific immunotherapy
      was performed with a standardized, aluminum hydroxide-adsorbed J. ashei extract
      with a potency of 100 IR (arbitrary index of reactivity) containing 54 microg of
      Jun a 1/ml (Alustal, Stallergenes, France). Subcutaneous injections started in
      October 2000. The maintenance dose was 0.30 ml of the 100-IR concentration per
      month. Rhinitis and conjunctivitis symptoms were rated according to a 4-point
      score. RESULTS: Seventeen patients from the treated group and 15 patients from
      the placebo group completed year 2001; 14 in each group completed year 2002. A
      statistically significant improvement (41%, p < 0.02) in the conjunctivitis
      symptom score was observed in actively treated patients compared to the placebo
      group at the peak of the 2001 pollen season. Improvement in rhinitis (17%) was
      not significant. This significant improvement was greater at the peak of the 2002
      pollen season (63%, p < 0.01). CONCLUSIONS: This study therefore indirectly
      validates the concept of treatment by major allergen because J. ashei is absent
      from the region in which this study was conducted.

PMID- 17228170
TI  - Severe immediate allergic reactions to grapes: part of a lipid transfer protein
      associated clinical syndrome.
AB  - BACKGROUND: Grape allergy is considered rare; grape lipid transfer protein (LTP;
      Vit v 1), an endochitinase and a thaumatin-like protein (TLP) have been reported
      as grape allergens. A considerable number of patients have referred to our
      department for severe reactions to grapes, and several IgE binding proteins were
      detected. OBJECTIVES: The aim of this study was to identify and characterise the
      allergens involved in severe allergic reactions to grapes and describe the
      population in which they occur. METHODS: Patients with reported severe allergic
      reactions to grapes (n = 37) are described. Grape allergens were
      purified/fractionated by a combination of chromatographic techniques, identified
      by proteomic analysis and biochemically characterised. Immunoreactivity was
      assessed by blot (inhibitions) and RAST (inhibitions), and skin prick tests were
      performed with the isolated allergens. RESULTS: All subjects were polyallergic,
      sensitised and reactive to several additional foods and pollen. All patients were
      sensitised to grape LTP. A 28-kDa expansin, a 37.5-kDa polygalacturonase
      inhibiting protein, a 39-kDa beta-1,3-glucanase and a 60-kDa protein were
      identified as minor grape allergens. Endochitinase and TLP did not play a role.
      Inhibition experiments revealed the possible cross-reactive role of LTP for
      clinical sensitivities to other LTP-containing plant foods, but also the
      involvement of cross-reactive carbohydrate determinants of minor allergens in IgE
      cross-reactivity. CONCLUSIONS: LTP is the major grape allergen, while additional
      minor allergens may contribute to clinical reactivity. Severe grape allergy
      presents in atopic patients who frequently react to other LTP-containing, plant
      derived foods. The 'LTP syndrome' is the appropriate term to describe this
      condition.

PMID- 17228171
TI  - Continuous ambulatory peritoneal dialysis peritonitis: broth inoculation culture
      versus water lysis method.
AB  - BACKGROUND/AIM: In the setting of empiric antibiotic treatment of peritoneal
      dialysis-related peritonitis complications, the speed with which a
      bacteriological diagnosis can be achieved is of importance. We compare the
      clinical performance of two culture methods to diagnose the causative
      microorganisms as suggested by the International Society for Peritoneal Dialysis
      and the United Kingdom Health Protection Agency. METHODS: We prospectively
      evaluated microbiological cultures of peritoneal fluid samples by the direct
      broth culture versus water lysis. Samples from 17 consecutive patients with
      dialysis-associated peritonitis were examined. RESULTS: Of the 17 dialysates
      cultured, 14 (82.4%) were positive by one of the two methods. The final culture
      results agreed in 16 of 17 specimens (94.1%). The preliminary organism
      identification rate by Gram staining with the broth culture method was 70.6%,
      which was significantly greater than 17.6% by the water lysis method (p =
      0.0019). In particular, the broth culture technique demonstrated superior Gram
      stain performance to identify Gram-positive organisms. Among the 13 dialysate
      samples positive by both methods, the broth culture method detected organisms
      faster than the water lysis method (1.3 +/- 0.7 vs. 2.6 +/- 1.6 days, p = 0.005).
      CONCLUSIONS: Our results support the routine use of the broth culture technique
      using BacT/Alert blood culture bottles in order to facilitate early streamlining
      of empiric antibiotic therapy. Gram staining of sediments after centrifugation is
      associated with low diagnostic yield. Whether the lysis-centrifugation technique
      could provide additional value in case of peritonitis with a high likelihood of
      culture-negative results needs to be evaluated.

PMID- 17228172
TI  - Seasonal variation of serum lipid levels in stable renal transplant recipients.
AB  - BACKGROUND/AIMS: Seasonal variation in lipid levels is well described in the
      general population, but has not been examined in renal transplant recipients
      (RTR). We sought to determine whether seasonal differences exist in RTR, a group
      at high risk for hyperlipidemia. METHODS: We reviewed our population of 920
      adults, identifying primary allograft recipients with survival > or =1 year,
      stable function, and > or =1 pair of post-6 months 'winter' (December 21 to March
      20) plus 'summer' (June 21 to September 22) fasting lipid measurements within the
      same year. Correlations between factors affecting lipids and lipid level change
      were followed by multiple linear regression analysis. RESULTS: 243 patients
      contributed 344 pairs. When most recent seasonal pair (n = 243) and all pairs (n
      = 344) were separately analyzed, no seasonal total cholesterol difference (winter
      vs. summer) was seen (5.08 vs. 5.05 mmol/l, p = 0.80; 5.11 vs. 5.09 mmol/l, p =
      0.81 respectively). Opposing variation was seen between hyperlipidemic and
      nonhyperlipidemic patients (0.08 vs. -0.18 mmol/l for winter minus summer, p =
      0.02). In multivariate analysis, seasonal cholesterol variation was predicted by
      level (p < 0.0001) and hemoglobin change (p = 0.01), while triglyceride variation
      was predicted only by level (p = 0.01). CONCLUSION: RTR do not exhibit seasonal
      variation in lipids, unlike the general population. Factors unique to RTR such as
      immunosuppressive therapies may act to suppress any seasonal effects.

PMID- 17228173
TI  - Prevalence of vitamin D deficiency and the safety and effectiveness of monthly
      ergocalciferol in hemodialysis patients.
AB  - BACKGROUND: Vitamin D deficiency is common in CKD and dialysis patients. Studies
      suggest a physiologic autocrine and/or paracrine role for 1,25(OH)D produced via
      1alpha-hydroxylase in tissues such as vascular smooth muscle, breast, prostate,
      and bone marrow. Studies have not yet defined the optimal dose and duration of
      vitamin D necessary to replete and maintain stores in dialysis patients, or
      whether it is safe or beneficial. METHODS: We performed a review of the
      prevalence of vitamin D deficiency and the safety and effectiveness of
      ergocalciferol oral supplementation (vitamin D(2), 50,000 IU monthly) given to
      hemodialysis patients during dialysis May to October 2005 in St. Louis (latitude
      38 degrees ). RESULTS: Among the 119-patient cohort present for the entire 6
      months, 25(OH)D was (mean +/- SD) 16.9 +/- 8.5 ng/ml, (91% < 30 ng/ml) and
      increased to 53.6 +/- 16.3 ng/ml (p < 0.001), (95% > 30 ng/ml, and none > 100
      ng/ml). Initial versus 6 mo. serum calcium (9.1 +/- 0.56 vs. 9.2 +/- 0.70),
      phosphorus (5.25 +/- 1.38 vs. 5.11 +/- 1.31), Ca x P, and paricalcitol dose (10.3
      +/- 9.6 vs. 11.3 +/- 9.2 mcg/week) were not significantly different. No
      hypercalcemia could be attributed to supplementation. Mean hemoglobin did not
      change significantly (11.96 +/- 1.4 vs. 11.69 +/- 1.4, p = 0.124), but most
      patients experienced a reduced weekly epoetin dose. Epoetin dose decreased in 64%
      of patients, and increased in 28%. CONCLUSIONS: We conclude that the vast
      majority of hemodialysis patients are vitamin D-deficient; monthly ergocalciferol
      50,000 IU is safe and effective in normalizing serum 25(OH)D levels and may have
      an epoetin-sparing effect.

PMID- 17228174
TI  - Involvement of transglutaminase-2 in pathological changes in renal disease.
AB  - BACKGROUND: Transglutaminase (Tg)-2 is shown to be related to renal fibrosis.
      However, its roles in human kidney disease have not been fully studied. METHODS:
      Using immunohistochemistry, we examined Tg-2 expression in renal biopsy specimens
      from 22 patients with IgA nephropathy (IgAN) and correlated the intensity of Tg-2
      staining with clinical and histopathological parameters. We compared the
      distribution and intensity of Tg-2 staining with those of transforming growth
      factor (TGF)-beta staining. RESULTS: In normal human kidneys, Tg-2 staining was
      not significant. In IgAN kidneys, glomerular Tg-2 staining correlated with serum
      creatinine (S-Cr), creatinine clearance (Ccr), urinary protein excretion,
      glomerular sclerosis, and mesangial cell proliferation. Tubulointerstitial Tg-2
      correlated with S-Cr, Ccr, N-acetyl-beta-glucosaminidase, urinary beta(2)
      microglobulin, and tubulointerstitial injuries. Tg-2 staining in the vicinity of
      vascular poles of glomeruli preceded the development of mesangial lesions, and
      was more remarkable in cases with renal impairment. The distribution and
      intensity of Tg-2 staining were not consistent with those of TGF-beta staining.
      In glomerular crescents, Tg-2 staining was remarkable. CONCLUSION: The present
      study showed a correlation between Tg-2 expression and renal function and
      pathological changes. Tg-2 expression in the vicinity of vascular poles was
      notable because that may be an initial marker of glomerular injury.

PMID- 17228175
TI  - Functional magnetic resonance imaging is more reliable than somatosensory evoked
      potential or mapping for the detection of the primary motor cortex in proximity
      to a tumor.
AB  - The accurate localization of the primary motor cortex (M1) is critical for the
      preservation of motor function during resection of brain tumors in and around the
      M1. The goal of the present study was to determine which technique provided the
      most accurate localization of M1. The accuracy of preoperative functional
      magnetic resonance imaging (fMRI), intraoperative somatosensory evoked potential
      (SEP) and cortical mapping for the localization of M1 was determined in 17
      patients with brain tumors in and around the M1. Because localization of the M1
      is typically symmetrical in the cerebral hemispheres, the M1 on the affected side
      was localized by determination of the M1 location on the unaffected side using
      fMRI with patient hand clenching. The location of M1 was successfully determined
      by SEP in 5 of 11 cases. In the remainder of cases, the sulcus at which phase
      reversal occurred during SEP was shifted 1 or 2 gyri rostral to the central
      sulcus. The location of M1 was successfully determined by brain mapping in 9 of
      15 cases. In the remainder of cases, stimulation failed to elicit a motor
      response. Finally, the location of M1 was successfully determined by fMRI in 16
      of 17 cases. These data indicate that fMRI was more reliable than SEP or brain
      mapping for the detection of M1 in proximity to a tumor.

PMID- 17228176
TI  - Gamma-knife-based stereotactic radiosurgery for uveal melanoma.
AB  - Nineteen patients with uveal melanoma were treated with Gamma-Knife-based
      stereotactic radiosurgery (SRS). The radiation dose was 40 Gy prescribed to the
      50% isodose line for all patients. The median follow-up was 40 months. The 3- and
      5-year overall survival rates were 86 and 55%, respectively. The 3- and 5-year
      tumor control rates were both 94%. Six of the 19 treated patients (32%) developed
      distant metastasis 31-75 months after SRS. Out of the 19 patients treated with
      SRS, 2 had improved, 4 had stable and 13 had worse vision in the treated eye.
      Gamma-Knife-based SRS appears to provide excellent local control of uveal
      melanoma. The risk of distant metastasis is significant. Effective systemic
      therapy is to be explored to improve the treatment outcome of uveal melanoma.

PMID- 17228177
TI  - Neuropsychological effects of bilateral deep brain stimulation of the subthalamic
      nucleus in Parkinson's disease.
AB  - OBJECTIVE: Although a relatively new technique, bilateral deep brain stimulation
      (DBS) of the subthalamic nucleus (STN) for the treatment of advanced cases of
      Parkinson's disease (PD) shows considerable promise. While the benefits of the
      STN stimulation for the treatment of motor symptoms of PD are well established,
      some studies have reported negative neuropsychological outcomes, especially in
      elderly patients. The objective of the present study was to investigate the
      neuropsychological effects of bilateral STN-DBS in a small sample of elderly
      patients with PD. METHODS: Six patients with PD (mean age 73.0 +/- 10.45 years)
      were assessed both before and approximately 6 months after DBS surgery in six
      neuropsychological domains. These domains included orientation, estimated IQ,
      attention/working memory, language, memory, and visual-spatial functioning.
      Additionally, depressive symptoms were assessed using the Geriatric Depression
      Scale. Daily doses of antiparkinsonian medications, in levodopa equivalents, were
      also compared pre- and postoperatively. RESULTS: Antiparkinsonian medications
      were reduced postoperatively by a mean of 65%, from a mean levodopa equivalent
      dosage of 987 mg/day to 346 mg/day. Category fluency, a word generation task
      within the language domain, was the only test in which participants demonstrated
      a statistically significant decline in performance. Participants demonstrated a
      mean score decrease of 41% (p < 0.05) in category fluency. CONCLUSIONS: The
      pathophysiology of the observed deficit remains ill defined. However, despite a
      small sample size, the study provides further evidence that bilateral STN-DBS in
      PD patients can be associated with negative neuropsychological outcome in word
      fluency, especially in elderly patients. Implications regarding patient selection
      for bilateral STN-DBS and recommendations for future research are further
      discussed.

PMID- 17228178
TI  - Bilateral stereotactic amygdalotomy for self-mutilation disorder. Case report and
      review of the literature.
AB  - Bilateral stereotactic amygdalotomy for the management of patients with severe
      aggressive behavior disturbances was first introduced by Hideki Narabayashi in
      1961. Since then, more than 500 cases have been reported in scientific
      literature, with a variety of cited behavior improvement rates. The advances of
      psychopharmacology along with the existent skepticism of the medical community in
      regards to psychosurgery have resulted in a dramatic decrease in the number of
      amygdalotomies performed worldwide. In our current communication, we report a
      case of bilateral stereotactic amygdalotomy for a medically refractory self
      mutilation disorder. We also review the pertinent literature with an emphasis on
      the selection of the most appropriate anatomical targets, the procedure-related
      complications and the outcomes of this occasionally helpful procedure.

PMID- 17228179
TI  - Petrous bone Langerhans cell histiocytosis treated with radiosurgery.
AB  - Langerhans cell histiocytosis (LCH) is a rare disease that may show as a solitary
      or multifocal lesion of bone, soft tissue or viscera. Involvement of the temporal
      bone has been described in 15-61% of patients with LCH, usually in association
      with multisystemic involvement. We report the case of a 30-year-old man
      presenting with vertigo and fluctuating hearing loss caused by monosystemic LCH
      of the left petrous bone. The patient was treated with radiosurgery (covering
      dose 10 Gy at 85% isodose, maximum dose 11.76 Gy). Two years after treatment, no
      evidence of recurrent disease was found in the CT scan or MRI. We discuss the
      treatment of temporal bone LCH, traditionally based on surgery, low-dose
      radiation therapy and intralesional steroids. To our knowledge, this is the first
      reported case of LCH of the petrous bone successfully treated with radiosurgery.
      This approach may be interesting in cases of LCH located on nonaccessible areas
      of the temporal bone.

PMID- 17228180
TI  - Pilot study of web-based bronchoscopy education using the Essential
      Bronchoscopist in developing countries (Mozambique and Mauritania).

PMID- 17228181
TI  - Age at growth hormone therapy start and first-year responsiveness to growth
      hormone are major determinants of height outcome in idiopathic short stature.
AB  - AIM: To develop methods to identify factors associated with a favorable outcome
      in GH-treated children with idiopathic short stature (ISS). METHODS: From 4,685
      children listed as having ISS within KIGS (Pfizer International Growth Database),
      we studied (a) the prediction model group (n = 657) to develop the first-year
      prediction model, and (b) the near adult height group (NAH; n = 256) which
      received GH for >4 years to develop descriptive models for adult height and
      overall height gain. RESULTS: NAH group at GH start: age was 10.0 years, height 
      2.5 SD score (SDS), weight -2.3 SDS, height minus mid-parental height (MPH) -1.5
      SDS; GH dose 0.19 mg/kg/week. Height gain was 1.1 SDS at a median age of 17.2
      years. Growth response correlated positively with GH dose and weight at the start
      of GH treatment, and negatively with age and height SDS minus MPH SDS. The model
      explains 39% (error SD 1.2 cm) of the variability. Adult height correlated (R(2)
      = 0.64) positively with height at GH start, MPH and the first-year responsiveness
      to GH, and negatively with age. CONCLUSIONS: Prepubertal children with ISS who
      show an appropriate first-year response to GH are likely to benefit from long
      term treatment, even on low GH dosages.

PMID- 17228182
TI  - RSO interview with Shan Marlette. Interview by Rene Michel.

PMID- 17228183
TI  - Beta radiation shielding with lead and plastic: effect on bremsstrahlung
      radiation when switching the shielding order.
AB  - Lead and plastic are commonly used to shield beta radiation. Radiation protection
      literature is ubiquitous in advising the placement of plastic first to absorb all
      the beta particles before any lead shielding is used. This advice is based on the
      well established theory that radiative losses (bremsstrahlung production) are
      more prevalent in higher atomic number (Z) materials than in low Z materials.
      Using 32P beta radiation, we measured bremsstrahlung photons transmitted through
      lead and plastic (Lucite) shielding in different test configurations to determine
      the relative efficacy of lead alone, plastic alone, and the positional order of
      lead and plastic. With the source (32P) and detector held at a constant
      separation distance, we inserted lead and/or plastic absorbers and measured the
      reduction in bremsstrahlung radiation level measured by the detector. With these
      test conditions, analysis of measured bremsstrahlung radiation in various
      thicknesses and configurations of lead and plastic shielding shows the following:
      placing plastic first vs. lead first reduces the transmitted radiation level only
      marginally (10% to 40%); 2 mm of additional lead is sufficient to correct the
      "mistake" of placing the lead first; and for equal thicknesses or weights of lead
      and plastic, lead is a more efficient radiation shield than plastic.

PMID- 17228184
TI  - Assessment of potassium iodide (KI) distribution program among communities within
      the emergency planning zones (EPZ) of two nuclear power plants.
AB  - The primary objective of this study was to evaluate a joint state and local
      government-sponsored potassium iodide (KI) distribution program in New Jersey.
      This program is part of a radiological emergency response system for residents
      living within the Emergency Planning Zones (EPZs) of nuclear power facilities. KI
      pills and an informational fact sheet were distributed locally at six different
      public clinics in the summer of 2002. In this study, a mailed survey was
      developed, pilot tested, and sent to the general public to assess knowledge about
      KI use. The survey consisted of two groups of people, those who attended a KI
      distribution clinic and those that did not attend a clinic. There was a
      statistically significant difference in knowledge among the two groups of survey
      respondents regarding KI prophylaxis, with a mean of 46% of survey questions
      answered correctly by those who attended a clinic vs. 15% by those who did not
      attend. Certain questions were problematic for the public to answer correctly and
      included potential low compliance with government instructions for taking KI,
      confusion regarding where the public can obtain KI pills during an emergency, and
      the lack of awareness on the proper use of KI for children, pregnant women, and
      persons over the age of 40 y. Additional outreach in these specific areas is
      warranted. This study also found that there was a highly variable geographic
      pattern of homes that have a supply of KI pills, with some areas having 60% of
      the households supplied with pills from the clinic while other areas had as low
      as 1% of the homes supplied with KI pills.

PMID- 17228185
TI  - Optimization of radioactive waste storage.
AB  - In several countries, low-level radioactive wastes are treated and stored
      awaiting construction and operation of a final repository. In some cases, interim
      storage may be extended for decades requiring special attention regarding
      security issues. The International Atomic Energy Agency (IAEA) recommends
      segregation of wastes that may be exempted from interim storage or ultimate
      disposal. The paper presents a method to optimize the decision making process
      regarding exemption vs. interim storage or ultimate disposal of these wastes.

PMID- 17228186
TI  - Design and simulation of a neutron facility.
AB  - State and other regulatory entities require that for any facility housing a
      particle accelerator the surrounding areas must be restricted to public access
      unless the dose equivalent rate is less than 0.02 mSv h at 5 cm from any
      accessible wall surrounding the facility under conditions of maximum radiation
      output. A Monte Carlo radiation transport simulation code, MCNP5, was used to
      design a proposed facility to shield two D-T neutron generators and one D-D
      neutron generator. A number of different designs were simulated, but due to cost
      and space issues a small concrete cave proved to be the best solution for the
      shielding problem. With this design, all of the neutron generators could be used
      and all of the rooms surrounding the neutron facility could be considered
      unrestricted to public access. To prevent unauthorized access into the restricted
      area of the neutron facility, light curtains, warning lights, door interlocks,
      and rope barriers will be built into the facility.

PMID- 17228189
TI  - Evaluation of two commercially available portal monitors for emergency response.
AB  - The Human Monitoring Laboratory has compared two types (the P3 and the
      MiniSentry) of portal monitors that can be field deployed in response to an
      emergency. They can be used to screen persons for internal or external
      radioactive contamination by fission activation products (neither unit is capable
      of detecting alpha or beta radiation, and the amount of material required to
      alarm the monitors is unacceptably high for low energy x rays or gamma rays)
      following an incident involving the release of radioactive material (accidental
      or intentional). It was found that the P3 benefits from simplicity but requires
      slightly more activity to alarm than the MiniSentry, although for emergency
      response, the amount of activity that can be detected is far below a level where
      significant health effects will occur. The MiniSentry was found to have more
      capability than the P3, but these benefits also bring their own disadvantages. It
      was also found that the MiniSentry would be difficult to deploy in an outdoor
      setting whereas the P3 is well designed for a field setting. Despite the
      differences found, the HML has concluded that both have a distinct place in
      emergency monitoring. In the future, the HML plans to have both instruments ready
      for field deployment.

PMID- 17228187
TI  - Radiation safety protocol for high dose 131I therapy of thyroid carcinoma in
      patients on hemodialysis for chronic renal failure.
AB  - Iodine ablation therapy for thyroid cancer on patients receiving dialysis poses
      unique radiation safety challenges. Exposure to gamma and beta negative particles
      by the hemodialysis (HD) staff is a concern that has not been well studied. A 53
      y-old male patient on HD for chronic renal failure was scheduled for 131I high
      dose therapy as treatment for thyroid papillary carcinoma. The patient was on HD
      every other day, prior to ablation. A high dose of 131I (3,607.5 MBq) was
      required. The patient was admitted for 131I therapy, and continued HD. Thyroid
      cancer ablation therapy was administered according to our institutional protocol.
      New radiation safety measures were developed and implemented in order to give the
      patient an optimal treatment dose, reduce radiation to the patient (critical
      organs and whole body), and to protect the HD personnel. This included placing
      two lead shields between the patient and the HD nurse, and HD monitoring by two
      alternating nurses to reduce their radiation exposure. Film badges were used to
      measure radiation exposure to the nursing staff. Dosimetry calculations were
      obtained to determine radiation absorbed doses by the optic lens, skin, and whole
      body. Quality control verification for this shielding arrangement proved to be
      effective in protecting the HD staff against gamma and beta negative radiation
      from recent 131I high dose therapy. Implementation of this model proved to be an
      effective and adequate radiation safety protocol for limiting radiation exposure
      to the HD staff. The patient was given 3607.5 MBq for optimal treatment after HD.
      Hemodialysis was repeated after approximately 48 and 96 h to remove excess 131I
      and reduce radiation to the patient.

PMID- 17228190
TI  - A prediction of accelerator-produced activation products.
AB  - The operational radiation protection issues associated with the Z-Machine
      accelerator located at Sandia National Laboratories are large: a variety of
      materials can be placed into the machine; these materials can be subjected to a
      variety of nuclear reactions, producing a variety of activation products. Without
      full understanding of the most likely contaminants, a realistic identification of
      the radiological hazards and appropriate controls is not possible. This paper
      presents a process developed to provide a realistic prediction of the accelerator
      produced radionuclides of interest.

PMID- 17228191
TI  - Contamination during a brachytherapy procedure.
AB  - This paper describes an unusual contamination incident that occurred during the
      treatment of a prostate cancer patient with seeds containing 125I. The incident
      became particularly interesting as the radiation safety procedures in place prior
      to the incident were, in fact, inappropriate for the type of incident that
      occurred, resulting in a series of response errors. Strands containing 108 125I
      seeds with a total activity of 1.61 GBq (43.6 mCi) were implanted into a
      patient's prostate and the patient was sent to the recovery room. A radiation
      survey detected radiation levels of up to 15 microR h(-1), 10 cm from the surface
      of the implantation needles. Multiple individuals entered the room and were
      potentially exposed to contamination. Contamination was detected in a sample of
      the patient's urine, indicating that one or more implanted seeds were leaking.
      Initial test results for staff showed that 12 of 15 had thyroid levels
      potentially above their corresponding minimum detectable activity levels, with
      calculated thyroid burdens ranging from 0.17 kBq to 0.94 kBq, but, subsequent
      measurements, using each staff member's thigh counts as background, suggested
      that no staff member had been contaminated. The patient showed high uptake of
      125I in his neck 10 d following the incident, estimated to correspond to an
      initial thyroid burden of 58 kBq. The possibility of contamination was not
      immediately considered due to the suspicion of the more common problem of a
      misplaced source. The initial measurements suggesting thyroidal contamination in
      staff point to an error in our thyroid screening method.

PMID- 17228194
TI  - Transparency in reimbursement policy rewards clinical excellence: the pay-for
      performance era means quality and revenue are no longer separate issues for
      healthcare providers.

PMID- 17228195
TI  - Infusion nursing standards of practice.

PMID- 17228196
TI  - Hematologic disorders associated with human immunodeficiency virus and AIDS.
AB  - Nurses encounter patients with human immunodeficiency virus infection at various
      stages of their infection and in a variety of settings. This article focuses on
      the most common hematologic disorders associated with human immunodeficiency
      virus infection and acquired immunodeficiency syndrome, which can precipitate
      complications and frequently accompany hospitalization. It is important for
      nurses to have a solid foundation as to the cause of these disorders, their
      impact on quality of life and outcomes, and management strategies.

PMID- 17228197
TI  - A proactive approach to combating venous depletion in the hospital setting.
AB  - This study focuses on the effects of infusion nurse specialists on the culture of
      an institution as it relates to infusion therapy practice. During the 18-month
      study, data were gathered on the outcomes of the proactive approach instituted by
      the infusion specialists. Outcomes assessed included phlebitis prevalence,
      peripherally inserted catheter placements, patient satisfaction scores, and ratio
      of catheters being placed by interventional radiology to the bedside placements.
      The study discusses the methods used by the infusion team in an attempt to change
      the approach to infusion therapy.

PMID- 17228198
TI  - Development of an evaluation tool for a clinical practice guideline on nursing
      assessment and device selection for vascular access.
AB  - This study developed and tested a chart audit tool to assess the implementation
      of evidence-based recommendations for vascular access nursing assessment and
      device selection. Chart audits of 71 patients were conducted in a home healthcare
      agency and a community hospital prior to guideline implementation. Observations
      of initial infusion therapy and chart audit documentation of 31 patients were
      also compared. Results from observations indicated that nurses provided care
      consistent with the recommendations, but findings from chart audits indicated
      that assessment and decisionmaking were poorly documented. Studies that use only
      precomparison and postcomparison by chart audit may miss changes in nursing
      practice.

PMID- 17228202
TI  - Operational definition of moist wound healing.

PMID- 17228203
TI  - Qualitative research proposals--Part I: Posing the problem.

PMID- 17228205
TI  - Pressure mapping.

PMID- 17228206
TI  - Are ankle and toe brachial indices (ABI-TBI) obtained by a pocket Doppler
      interchangeable with those obtained by standard laboratory equipment?
AB  - PURPOSE: The aim of this study was to determine if the ankle and toe brachial
      indices obtained by an experienced registered nurse (RN) using a pocket Doppler
      were within acceptable levels of agreement with those obtained by a registered
      vascular technologist (RVT) using standard laboratory equipment. DESIGN: A within
      subjects comparative design was used. SETTING AND SUBJECTS: Thirty subjects who
      were referred to a vascular laboratory for arterial studies were recruited. All
      tests were performed in the outpatient vascular laboratory of a large, urban
      medical center. METHODOLOGY: Ankle and toe brachial indices were measured on each
      subject by the RN and the RVT during each visit. Data were analyzed using the
      Bland-Altman method to assess the level of agreement between the RN's pocket
      Doppler and the RVT's standard laboratory equipment. RESULTS: Differences between
      each instrument's ankle brachial indices were within the a priori 15% limit of
      agreement. Differences between each instrument's toe brachial indices exceeded
      the a priori 15% limit of agreement. CONCLUSION: The ankle brachial index
      obtained by using a pocket Doppler by an experienced RN is interchangeable with
      vascular laboratory testing for detection of lower extremity arterial disease
      (LEAD). The pocket Doppler-derived toe brachial index was not interchangeable
      with vascular laboratory testing for detection of LEAD.

PMID- 17228207
TI  - Incontinence-associated dermatitis: a consensus.
AB  - Incontinence-associated dermatitis (IAD) is an inflammation of the skin that
      occurs when urine or stool comes into contact with perineal or perigenital skin.
      Little research has focused on IAD, resulting in significant gaps in our
      understanding of its epidemiology, natural history, etiology, and
      pathophysiology. A growing number of studies have examined clinical and economic
      outcomes associated with prevention strategies, but less research exists
      concerning the efficacy of various treatments. In the clinical and research
      settings, IAD is often combined with skin damage caused by pressure and shear or
      related factors, sometimes leading to confusion among clinicians concerning its
      etiology and diagnosis. This article reviews existing literature related to IAD,
      outlines strategies for assessing, preventing, and treating IAD, and provides
      suggestions for additional research needed to enhance our understanding and
      management of this common but under-reported and understudied skin disorder.

PMID- 17228209
TI  - Survey of wound, ostomy and continence (WOC) nurse clinicians on stomal and
      peristomal complications: a content validation study.
AB  - PURPOSE: Validated and reliable stomal and peristomal complication definitions
      and associated interventions are lacking. Available literature is either narrowly
      medically focused or only of case study level. The objectives of this study were
      to establish content validation data for the proposed stomal and peristomal
      complication definitions and their associated interventions, to obtain the data
      related to contact with stomal and peristomal complication patients, and to gain
      insight into the ostomy care process. METHODS: A researcher-designed survey was
      sent to 2900 expert Wound, Ostomy and Continence nurse clinicians via a national
      mailing to a representative nonrandomized sample of participants who identified
      that they included ostomy care in their professional practice. In total, 686
      nurses returned the survey, a response rate of 24%. The purposive sample was
      asked to quantify the degree of validity of the survey's stated stomal and
      peristomal definitions and interventions. Hand-written qualitative comments of
      the participants were transcribed, analyzed, and themes were derived. RESULTS: On
      a scale of 1 to 4, the mean score for all definitions and interventions was 3.64
      (SD=0.30). The overall survey's content validity index was .91. Ratings
      demonstrated high consensus validation on the stomal and peristomal definitions
      and interventions, with definitions scoring higher. The mean scores and the
      content validity index results on selected items were slightly lower for
      interventions, especially stomal interventions. Qualitative analysis of
      participants' comments about the whole instrument generated 10 themes and
      associated subthemes related to omitted complications and interventions and
      general observations about the ostomy care process and the validation research
      process. CONCLUSION: The proposed stomal and peristomal definitions and
      interventions were rated as generally valid. Further research documenting
      validation of participants' comments is necessary. Given the findings, additional
      complications and interventions not identified in the literature were noted and
      need to be further scrutinized and researched.

PMID- 17228210
TI  - Difficulties experienced by the ostomate after hospital discharge.
AB  - PURPOSE: This descriptive study used a mailed survey to identify difficulties
      related to the stoma that ostomates experience after discharge from the hospital,
      who they sought help from, and if the advice was perceived as helpful. SUBJECTS
      AND SETTING: Ostomates who are 18 years or older and have undergone a urinary or
      fecal diversion at a North Carolina hospital between January 1, 2003 and June 30,
      2005, were asked to respond to a survey about the difficulties related to their
      ostomy. INSTRUMENT: The survey gathered demographic and anthropometric data,
      information regarding stomal complications, self-evaluation of emotional state,
      and contact with clinicians and support groups. RESULTS: Of the 140 surveys
      mailed, 43 were returned, demonstrating a return rate of 31%. Thirty-four
      returned surveys were useable for statistical analysis. The top 5 difficulties
      experienced by the respondents were peristomal skin irritation (76%), pouch
      leakage (62%), odor (59%), reduction in previously enjoyed activities (54%), and
      depression/anxiety (53%). Twenty percent of the ostomates who experienced
      difficulties after surgery did not seek help. Ostomates primarily sought help
      from nurses when they experienced problems related to the stoma and its
      maintenance. For mental health, sleep, and sexual problems, a medical doctor was
      the practitioner of choice. Ostomates were satisfied with most of the help they
      received from an ostomy nurse; satisfaction was lower for home health nurses and
      surgeon or primary care physician practices. Average wear time for a stoma pouch
      was 4 days. CONCLUSION: The majority of the ostomates experienced difficulty with
      pouch leakage, skin irritation, odor, depression or anxiety, and uneven pouching
      surfaces. Ostomates desire assistance with these problems and will benefit from
      long-term follow-up by an ostomy nurse.

PMID- 17228211
TI  - An introduction to genetics and application to Crohn's disease.
AB  - Gene-based diagnostics and therapeutics are being explored for application in
      many areas of healthcare. An understanding of the principles of genomics has
      become fundamental to patient care within all specialties of nursing and is
      expected to be included in certification exams in the near future. This
      introductory article is designed to provide practicing Wound, Ostomy, and
      Continence nurses with basic information to enhance their abilities to comprehend
      genetics information, apply it to practice, and translate it to colleagues and
      patients. Specifics about the genetic basis of Crohn's disease are used to
      illustrate the application of the concepts described in the article.

PMID- 17228212
TI  - Emergency department management and short-term outcome of children with
      constipation.
AB  - BACKGROUND: Constipation is a common diagnosis made in the pediatric emergency
      department (ED). Specific evidence-based standards for evaluation and treatment
      are lacking. OBJECTIVE: To describe variation in evaluation and treatment of
      constipation and characteristics and treatments associated with improvement.
      METHODS: This single-site descriptive study examined constipated children
      discharged from the ED. Chart review provided history, examination, evaluation,
      and treatment. Symptoms and on-going treatment were assessed by telephone
      interview at 4 to 6 weeks. Patients were dichotomized to poor versus adequate
      responders. Poor responders had 2 or more of the following: overall constipation,
      persistent presenting symptom, bowel movement frequency of less than once every
      other day, painful defecation, and/or abdominal pain. RESULTS: The study group
      had 121 patients, with mean age of 6.4 years; 54% were female. Abdominal pain was
      the most common complaint (66%); 46% reported hard/infrequent stools. Most (67%)
      had symptoms for less than 1 week. Many (41%) previously sought care for the same
      problem. Most (70%) had abdominal radiographs. One third received an enema in the
      ED, and most patients were prescribed laxatives, most commonly polyethylene
      glycol (80%). After an enema, 28% were discharged without constipation
      medication. At follow-up, 35% were using laxatives, and 27% had sought additional
      care. Nearly half (42%) were poor responders. Poor responders were younger (5.1
      vs. 7.3 years; P < 0.01). There was no difference in response based upon sex,
      duration of symptoms, or ED treatment. CONCLUSIONS: Although older children are
      more likely to improve, many constipated children continue to have symptoms. Type
      of ED therapy is unrelated to on-going symptoms at 4 to 6 weeks.

PMID- 17228213
TI  - Computer modeling of patient flow in a pediatric emergency department using
      discrete event simulation.
AB  - Increasing patient census and department overcrowding are universal concerns in
      pediatric emergency medicine. Accurate predictions of patient flow and resource
      utilization in the pediatric emergency department (PED) are important in
      determining what aspects of PED activity could be modified to improve patient
      flow, reduce patient waiting times, and increase staff efficiency and morale, and
      thus direct change more effectively. BACKGROUND: We report (1) the construction
      of a Patient Flow Model (PFM) using discrete event simulation to test simulated
      PED staffing scenarios that were designed to alleviate the pressures that result
      from increased census and overcrowding, and (2) a Physician Scheduling Analysis
      Tool to assist in physician scheduling. METHODS: Arena discrete event simulation
      modeling software was used to develop a model of PED patient flow after extensive
      interviews with PED staff and direct observation of patient flow in July 2005. A
      total of 517 patients were directly observed, and all modeled aspects of their
      interaction with PED staff and resources were recorded. Historical demographic
      patient arrival information was combined with observed patient flow data to
      provide simulated patient arrival rates for the PFM and was also used to
      construct the Physician Scheduling Analysis Tool. Validation of the PFM was
      performed by comparing annual simulated patient flow data with actual patient
      flow data. Previously determined staffing scenarios were applied to the
      simulation and the resulting performance indicator outputs examined. RESULTS: The
      PFM was validated on model-wide and process-specific levels, with excellent
      validation observed on high acuity-patient length of stay and for highly detailed
      processes such as triage and registration. Simulation of the addition of a
      hospital volunteer and a second triage nurse demonstrated reductions in pretriage
      waiting time and the proportion of patients waiting longer than 30 or 60 minutes
      for pretriage. Simulation of an extra physician shift to the staff schedule
      demonstrated reductions in length of stay for patients of all triage categories.
      CONCLUSIONS: The PFM accurately represents patient flow through the department
      and can provide simulated patient flow information on a variety of scenarios. It
      can effectively simulate changes to the model and its effects on patient flow.

PMID- 17228214
TI  - High-fidelity medical simulation as an assessment tool for pediatric residents'
      airway management skills.
AB  - OBJECTIVES: To evaluate high-fidelity medical simulation as an assessment tool
      for pediatric residents' ability to manage an acute airway. METHODS: We performed
      a prospective, observational study in which 16 pediatric residents were consented
      and then brought to the medical simulation center. They were placed in 2
      different computer-driven scenarios and asked to manage the cases. The first
      scenario was a 3-month-old infant with bronchiolitis and severe respiratory
      distress and was programmed to develop respiratory failure. The second case was a
      16-year-old adolescent with alcohol intoxication and respiratory depression and
      was programmed for emesis and aspiration. Both cases included a nurse, parent,
      and intern. We recorded performance of predetermined critical actions and any
      harmful actions. RESULTS: There were 47 attempts at intubation with 27 successes
      (56%). Appropriate preoxygenation was performed in 15 (47%) of 32 cases.
      Appropriate rapid sequence induction was administered in 21 (66%) of 32 cases.
      Cricoid pressure was applied in 20 (63%) of 32 cases. End-tidal carbon dioxide
      detector was used in 11 (34%) of 32 cases. A nasogastric tube was placed in 14
      (44%) of 32 cases. Harmful actions included rapid sequence induction administered
      before intubation equipment setup, bag-valve mask not connected to oxygen,
      inappropriate endotracheal tube size, pulling cuffed endotracheal tube out while
      inflated, and placing the laryngoscope blade on backwards. CONCLUSIONS: Our data
      identified many areas of concern with resident skills in managing an airway. This
      project suggests that high-fidelity medical simulation can assess a resident's
      ability to manage an airway as well as a program's effectiveness in teaching the
      skills necessary to manage an acute pediatric airway.

PMID- 17228215
TI  - Measurement accuracy of fever by tympanic and axillary thermometry.
AB  - As the basic sciences develop, temperature measurement methods and devices were
      improved. For hundreds of years both in clinics and home, mercury-in-glass
      thermometer was the standard of human temperature measurements. In this study, we
      aimed to compare tympanic infrared thermometers with the conventional temperature
      option, mercury-in-glass thermometer, which is historical standard in the
      clinical conditions. METHODS: A total of 102 randomly selected pediatric patients
      who admitted to our hospital were enrolled, and simultaneous temperature
      measurements were performed via axilla and external auditory canal with 3
      different techniques. For external auditory recordings, infrared tympanic First
      Temp Genius for clinical use and Microlife IR 1DA1 for home usage were used.
      Classic mercury-in-glass thermometers were used for axillary recording. For each
      method, 886 measurements were performed. RESULTS: The mean results of the
      axillary mercury-in-glass thermometers, infrared tympanic First Temp Genius, and
      Microlife IR 1DA1 were 36.8 +/- 0.7, 37.5 +/- 0.9, 36.9 +/- 0.8, respectively.
      The Bland-Altman plot of differences suggests that 95% of the infrared tympanic
      clinical use thermometer readings were within the limits of agreement, which is
      +0.27 and -1.75 degrees C range of mercury-in-glass thermometer. The Bland-Altman
      plot of differences suggests that 95% of the tympanic home-use thermometer
      readings were within the limits of agreement, which is +0.98 and -1.27 degrees C
      range of mercury-in-glass thermometer. In our group, 15% of the patients were
      misdiagnosed as febrile with home-use tympanic thermometer, whereas this
      percentage was 4% with clinical tympanic thermometer. Also, 5% and 31% of febrile
      patients were misdiagnosed as afebrile with clinical tympanic and home-use
      tympanic thermometer, if axillary mercury-in-glass thermometer recording defines
      fever. DISCUSSION: Our results showed that there is a significant difference in
      each recording with different thermometers, and this variance was present in both
      higher and lower readings. We recommend thathome-use infrared tympanic
      thermometer could be used for screening but must not be considered as a tool to
      decide patients follow-up.

PMID- 17228216
TI  - Sydenham chorea: a case report and review of the literature.
AB  - Sydenham chorea (SC) is the neurological manifestation of rheumatic fever and is
      the most common acquired chorea in children. The disease presents as choreiform
      movements and behavioral changes after a streptoccocal throat infection. Although
      the incidence of SC has diminished because of aggressive antibiotic treatment,
      both isolated cases and epidemics persist, necessitating emergency physicians to
      be familiar with the disease. We describe the case of a 9-year-old girl with SC.
      A discussion of the pathophysiology, clinical presentation, and management of SC
      in the emergency department follows.

PMID- 17228218
TI  - Spontaneous pneumomediastinum in children: a literature review.
AB  - Spontaneous pneumomediastinum (SPM) is a rare, generally benign condition in
      young children caused by alveolar rupture and dissection of air into the
      mediastinum and hilum. In children, SPM is seen most commonly in asthmatics but
      may also occur in any patient who induces a Valsalva maneuver, including
      coughing, forceful vomiting, or first-time wheezing. There are limited reports on
      SPM in first-time wheezing episodes. We report a case of a 4-year-old girl with
      no history of wheezing who presents with wheezing, mild respiratory distress, and
      salient radiographic findings of pneumomediastinum, including spinnaker sail sign
      and continuous diaphragm sign. The SPM is generally a benign entity that requires
      supportive care, and resolution occurs spontaneously. This article will allow the
      clinician to become familiar with the specific clinical and radiological signs
      associated with SPM.

PMID- 17228217
TI  - Isolated costal hyperostosis: a rare cause of severe hemothorax.
AB  - Chest pain due to hemothorax is rare. However, the possibility of traumatic
      hemothorax must always be suspected. We report a case of a 15-year-old girl with
      hemothorax after erosion of the intercostal artery of the left seventh rib by a
      histological proved solitary costal hyperostosis. She presented with a 2-month
      history of intermittent left-sided chest pain and 3 episodes of acute chest pain
      followed by dizziness and loss of consciousness. The chest radiograph revealed a
      large left pleural effusion and a thin-section chest computed tomography scan
      that was performed after drainage of the hemothorax indicated a spicule
      projecting inward into the chest from the left seventh rib. After thoracotomy, a
      solitary costal hyperostosis causing a traumatic pseudoaneurysm of the
      intercostal artery was removed by partial resection of the left seventh rib, the
      intercostals vessels were ligated, and the pseudoaneurysm excised.

PMID- 17228219
TI  - Ventricular septal defect secondary to a unique mechanism of blunt trauma: a case
      report.
AB  - We report the case of an adolescent boy who had progressive respiratory distress
      and cardiovascular compromise after striking his chest against his bicycle
      handlebars. An echocardiogram in the emergency department revealed a large
      ventricular septal defect. The boy did well after emergent operative repair and
      subsequent replacement of a torn tricuspid valve. The characteristics of
      ventricular septal defects from blunt trauma are briefly discussed.

PMID- 17228221
TI  - Review of medications used in juvenile rheumatoid arthritis.
AB  - Juvenile rheumatoid arthritis is a chronic condition. The goal of therapy is to
      control pain, preserve joint range of motion and function, minimize systemic
      complications, and assist in normal growth and development. Recent advances in
      understanding the pathophysiology of arthritis have expanded the treatment of
      this chronic condition. Many medications including nonsteroidal anti-inflammatory
      agents, disease-modifying antirheumatic drugs, biologic agents, and cytotoxic
      agents are available for treating juvenile rheumatoid arthritis. Emergency
      medicine physicians should be familiar with the different classes and adverse
      effects of these drugs.

PMID- 17228220
TI  - Redefining the community pediatric hospitalist: the combined pediatric
      ED/inpatient unit.
AB  - BACKGROUND: The use of pediatric hospitalists in community hospitals has
      increased over the past decade in response to the desire to provide high-quality
      pediatric care. Many hospitals are challenged to create financially independent
      and productive programs. OBJECTIVE: To evaluate an alternative approach to
      traditional community hospital pediatric care of having pediatricians work in a
      combined pediatric Emergency Department (PED)/inpatient unit. DESIGN/METHODS:
      Franklin Square Hospital Center converted its pediatric hospitalist program from
      a traditional inpatient with partial Emergency Department (ED) coverage program
      to one that covers a combined PED/inpatient unit. Outcome categories were
      compared between the year before opening, 2003, to the year after, 2004. Measures
      included total part B billing, overall patient satisfaction scores for the PED
      and inpatient unit from the Press Ganey patient satisfaction survey, perception
      of wait times and time to admission, and risk-adjusted inpatient length of stay
      (ALOS). RESULTS: Part B billings from the 5.5 Full Time Equivalent (FTE)
      pediatric hospitalists increased 82% from increased 61% from 2003 to 2004, from
      1,631,583 dollars in 2003 to 2,967,715 dollars in 2004 as a result of increased
      volume of ED patients seen by pediatricians. The mean inpatient satisfaction
      score did not significantly change, 75.7 in 2003 and 79.0 in 2004 (P = 0.432),
      but the mean PED score significantly increased from 75.8 to 83.4 (P = 0.0001).
      Mean scores of the efficiency measures on the survey increased for PED patients,
      with the mean score for wait time to treatment increasing from 62.0 to 75.3 (P <
      0.0001). Total throughput time through the ED improved significantly as well from
      143 minutes to 122 minutes (P = 0.0003). Risk-adjusted length of stay performance
      did not change; for calendar year 2003, the mean monthly ALOS was 1.883 (95%
      range 1.503, 2.263), compared with a 2004 mean monthly ALOS of 1.869 (95% range
      1.523, 2.216). CONCLUSIONS: Implementation of a combined PED/inpatient unit was
      associated with increased billing by hospitalists, increased satisfaction scores
      of ED patients, and decreased ED throughput times. Pediatric hospitalist programs
      that want to improve financial and patient outcomes in a community setting could
      consider adopting the combined unit approach.

PMID- 17228222
TI  - Swallowed a coin: well-maybe not.

PMID- 17228223
TI  - Pediatric anaphylaxis.

PMID- 17228225
TI  - ECGs in the ED.

PMID- 17228226
TI  - Pediatric emergency medicine: legal briefs.

PMID- 17228227
TI  - Diabetic ketoacidosis presenting with pneumomediastinum.

PMID- 17228229
TI  - Neurenteric cyst arising in the high convexity parietal lesion: case report.
AB  - OBJECTIVE: Supratentorial neurenteric cysts (NC) are rare; only 16 cases were
      reported previously, the majority of which were located in the anterior fossa or
      in the deep midline structure. We report a case of NC arising in the high
      convexity parietal lesion and briefly discuss the histogenesis of NC in such an
      unusual location. CLINICAL PRESENTATION: A 63-year-old man presented with a 1
      month history of progressive headache and dizziness. Computed tomographic and
      magnetic resonance imaging scans demonstrated a 4 x 5 x 5 cm extra-axial cystic
      lesion in the right parietal convexity adjacent to the sagittal sinus without
      contrast enhancement. A translucent thin-walled cyst containing a milky-white
      fluid was partially excised via a right parietal craniotomy. INTERVENTION: The
      cyst wall was composed of a thin fibroconnective tissue lined by a single layer
      of ciliated columnar epithelial cells and pseudostratified columnar epithelium.
      Mucous-secreting goblet cells of epithelial lining reacted to periodic acid-Shiff
      staining. The internal epithelial cells were immunoreactive to cytokeratin and
      epithelial membrane antigen, but not to carcinoembryonic antigen, glial
      fibrillary acidic protein, or S-100 protein. A follow-up magnetic resonance
      imaging scan taken 6 months later showed resolution of mass effect without
      evidence of cyst recurrence. The patient was discharged home in excellent
      condition. CONCLUSION: A case of NC arising in the high convexity parietal lesion
      is described. Supratentorial NCs located far from the location of the primitive
      endoderm suggest the possibility that NCs could arise from ectopic endodermal
      tissue through an undetermined process of anomalous differentiation. Total
      surgical excision of the cyst wall and contents is the best treatment for the
      symptomatic cases. Subtotal or partial resection without injury to important
      neurovascular structures are reasonable alternatives, but long-term careful
      follow-up magnetic resonance imaging or computed tomography is necessary to
      monitor for recurrence of any residual lesion.

PMID- 17228230
TI  - Spinal cord herniation into associated pseudomeningocele after brachial plexus
      avulsion injury: case report.
AB  - OBJECTIVE: Posttraumatic spinal cord herniation is a rare condition. We describe
      a case of spinal cord herniation into an associated pseudomeningocele after a
      brachial plexus avulsion injury. CLINICAL PRESENTATION: A 33-year-old man began
      to develop progressive Horner's syndrome 14 years after a brachial plexus
      avulsion injury. At a clinical presentation 17 years after that injury, sensory
      disturbance and a unilateral pyramidal sign were also evident. In addition to
      myelography and computed tomographic myelography findings, coronal magnetic
      resonance imaging scans clearly demonstrated herniation of the spinal cord into a
      large pseudomeningocele inside the C7-T1 intervertebral foramen. Another
      pseudomeningocele inside the T1-T2 intervertebral foramen was also noted.
      INTERVENTION: The patient underwent a C6-T2 laminectomy, during which the spinal
      cord was found to be herniated through a dural defect into a pseudomeningocele at
      the C8 root level, and a second dural defect was also shown, with an arachnoid
      outpouching that included an avulsed T1 root. The spinal cord herniation was
      reduced and the dural defects were repaired. After surgery, the patient showed no
      significant neurological changes, and his condition stabilized. CONCLUSION:
      Brachial plexus root avulsions may result in the formation of pseudomeningoceles
      and can lead to spinal cord herniation. Coronal magnetic resonance imaging is
      useful to demonstrate spinal cord herniation as well as pseudomeningoceles.
      Surgical treatment is recommended for such cases with progressive symptoms to
      prevent further deterioration.

PMID- 17228231
TI  - Delayed cerebral vasospasm secondary to bacterial meningitis after lumbosacral
      spinal surgery: case report.
AB  - OBJECTIVE: Delayed cerebral vasospasm is an under-recognized complication of
      meningitis. This case report is important because it is the first to definitively
      associate vasospasm with meningitis using catheter angiography. Furthermore, it
      is the first to correlate the time course of delayed cerebral vasospasm with
      meningitis. CLINICAL PRESENTATION: We present a patient who developed a partial
      expressive aphasia 9 days after developing meningitis, consistent with cerebral
      vasospasm, after lumbosacral spinal surgery. INTERVENTION: Vasospasm was
      confirmed by angiography and transcranial Doppler sonography, and symptoms
      responded to hypervolemia, hypertension, and hemodilution therapy. CONCLUSION: If
      a patient develops neurological symptoms consistent with a timeline of delayed
      cerebral vasospasm in the setting of meningitis, angiographic evaluation and
      appropriate therapy should be pursued.

PMID- 17228233
TI  - When the bone flap hits the floor.

PMID- 17228235
TI  - Outcome of oculomotor nerve palsy from posterior communicating artery aneurysms:
      comparison of clipping and coiling.

PMID- 17228237
TI  - Duration of in vivo antimicrobial activity of antibiotic-impregnated
      cerebrospinal fluid catheters.

PMID- 17228239
TI  - Natural history of intracranial atherosclerosis: a critical review.

PMID- 17228241
TI  - Outcome of surgical clipping of unruptured aneurysms as it compares with a 10
      year nonclipping survival period.

PMID- 17228243
TI  - Harvesting of the sural nerve using a stripper.

PMID- 17228245
TI  - Diagnosis, treatment, and analysis of long-term outcomes in idiopathic normal
      pressure hydrocephalus.

PMID- 17228249
TI  - Ribonucleic acid interference for neurological disorders: candidate diseases,
      potential targets, and current approaches.
AB  - OBJECTIVE: Ribonucleic acid (RNA) interference (RNAi) is a conserved evolutionary
      defense mechanism that is gaining utility for therapeutic application by
      modulating gene expression or silencing disease-causing genes. METHODS: This
      strategy has recently achieved success in mammalian cells via synthetic small
      interfering RNA or short hairpin RNA expressed in vectors for gene delivery. The
      vector-based RNAi strategy has particular potential because of the possibility of
      targeted gene delivery, long-term gene expression, and the potential means of
      penetrating the blood-brain barrier. RESULTS: RNAi-based approaches have been
      proposed for a variety of neurological disorders, including dominant genetic
      diseases, neurodegenerative diseases, malignant brain tumors, pain, and viral
      induced encephalopathies. CONCLUSION: This review summarizes the current
      approaches of the RNAi strategy for neurological disorders, focusing on potential
      targets for therapeutic intervention.

PMID- 17228250
TI  - The dopaminergic nigrostriatal system and Parkinson's disease: molecular events
      in development, disease, and cell death, and new therapeutic strategies.
AB  - For several decades, the clinical study of Parkinson's disease has driven an
      increasingly sophisticated understanding of the dopaminergic system and its
      complex role in modulating motor behavior. This article reviews salient areas of
      research in this field, commencing with the molecular biology of the development
      of the mesencephalic dopaminergic system. We then discuss events thought to be
      crucial in the cellular and molecular pathology of Parkinson's disease, proposed
      mechanisms of cell death, and relevant toxin models. These advancements are used
      as a template to review emerging therapeutic techniques, including
      neuroprotection strategies, surgical treatment of trophic factors, gene therapy,
      and neural transplantation.

PMID- 17228251
TI  - Stereotactic radiosurgery: adjacent tissue injury and response after high-dose
      single fraction radiation: Part I--Histology, imaging, and molecular events.
AB  - Radiosurgery is now the preferred treatment modality for many intracranial
      disease processes. Although almost 50 years have passed since it was introduced
      as a tool to treat neurological disease, investigations into its effects on
      normal tissues of the central nervous system are still ongoing. The need for
      these continuing studies must be underscored. A fundamental understanding of the
      brain parenchymal response to radiosurgery would permit development of strategies
      that would enhance and potentiate the radiosurgical treatment effects on diseased
      tissue while mitigating injury to normal structures. To date, most studies on the
      response of the central nervous system to radiosurgery have been performed on
      brain tissue in the absence of pathological lesions, such as benign tumors or
      metastases. Although instructive, these investigations fail to emulate the
      majority of clinical scenarios that involve radiosurgical treatment of specific
      lesions surrounded by normal brain parenchyma. This article is the first in a two
      part series that addresses the brain parenchyma's response to radiosurgery. This
      first article analyzes the histological, radiographic, and molecular data
      gathered regarding the brain parenchymal response to radiosurgery and aims to
      suggest future studies that could enhance our understanding of the topic. The
      second article in the series begins by discussing strategies for radiosurgical
      therapeutic enhancement. It concludes by focusing on strategies for mitigation
      and repair of radiation-induced brain injury.

PMID- 17228252
TI  - Extended endoscopic endonasal transsphenoidal approach for the removal of
      suprasellar tumors: Part 2.
AB  - OBJECTIVE: The widespread use of the endoscope in transsphenoidal pituitary
      surgery has recently contributed to the extension of the approach beyond the
      tuberculum sellae and planum sphenoidale for the management of lesions located in
      the suprasellar area, either with an endoscope-assisted or purely endoscopic
      technique. Based on our previous experience with more than 450 standard
      endoscopic transsphenoidal operations, we have retrospectively evaluated the
      effectiveness of the extended endoscopic endonasal transsphenoidal approach in
      the management of lesions mainly located in the suprasellar area. METHODS:
      Between January 2004 and December 2005, 20 consecutive patients underwent
      extended endoscopic endonasal transsphenoidal surgery for a total of 21
      procedures. The series consisted of seven pituitary adenomas, seven
      craniopharyngiomas, three suprasellar Rathke's cleft cysts, two tuberculum sellae
      meningiomas, and one pilocytic astrocytoma of the chiasm. RESULTS: Tumor removal,
      as assessed by postoperative magnetic resonance imaging, revealed complete
      removal of the lesion in four out of seven pituitary adenomas, five out of seven
      craniopharyngiomas, three out of three Rathke's cleft cysts, and two out of two
      tuberculum sellae meningiomas. One patient (5%) with craniopharyngioma had a
      postoperative cerebrospinal fluid leak that required reoperation. The same
      patient experienced a sphenoid mycosis, which was treated with medical therapy.
      Some specific conditions associated with the anatomy of the surgical route, as
      well as to the morphology of the lesion, have resulted to condition the
      feasibility of the approach. CONCLUSION: Small and medium sized suprasellar
      lesions located in the midline, with or without a limited parasellar extension
      and without involvement of vascular structures, seem amenable to be resected
      through such extended endoscopic transsphenoidal approach. Improvements in
      closure techniques and the use of new materials and surgical glues seem to
      significantly reduce the postoperative cerebrospinal fluid leak rate and
      meningitis.

PMID- 17228253
TI  - Risk of malignancy after gamma knife stereotactic radiosurgery.
AB  - OBJECTIVE: To assess the risk of radiosurgery to cause malignant transformation
      in benign tumors or to induce new malignancies. METHODS: A retrospective cohort
      study comparing the Sheffield, England, radiosurgery patient database with
      national mortality and cancer registries. This data set comprises approximately
      5000 patients and 30,000 patient-years of follow-up, with more than 1200 patients
      having a follow-up period longer than 10 years. RESULTS: In this material, a
      single new astrocytoma was diagnosed, whereas, based on national incidence
      figures, 2.47 cases would have been predicted. CONCLUSION: No increased risk of
      malignancy was detected in this series, supporting the safety of radiosurgery.
      Pragmatically, in advising patients, the risks of malignancy would seem small,
      particularly if such risks are considered in the context of the other risks faced
      by patients with intracranial pathologies requiring radiosurgical treatments.

PMID- 17228254
TI  - Intraoperative subcortical language tract mapping guides surgical removal of
      gliomas involving speech areas.
AB  - OBJECTIVE: Subcortical stimulation can be used to identify functional language
      tracts during resection of gliomas located close to or within language areas or
      pathways. The objective of the present study was to investigate the feasibility
      of the routine use of subcortical stimulation for identification of language
      tracts in a large series of patients with gliomas and to determine the influence
      that subcortical language tract identification exerted on the extent of surgery
      and on the appearance of immediate and definitive postoperative deficits.
      METHODS: Subcortical stimulation for language tract identification was
      systematically used during surgical removal of 88 gliomas (44 high-grade and 44
      low-grade gliomas) involving language pathways. Procedures were performed during
      asleep/awake craniotomy. Subcortical stimulation was continuously alternated with
      surgical resection in a back-and-forth fashion. Language performances were tested
      by neuropsychological language evaluation preoperatively and at 3, 30, and 90
      days after surgery. RESULTS: Language tracts were identified in 59% of patients,
      with differences according to tumor location but not according to histological
      grade. Language tract identification influenced the ability to reach a complete
      tumor removal in low-grade gliomas, in which tracts were documented inside the
      peripheral mass of the tumor. Identification of language tracts was associated
      with a higher occurrence of transient postoperative deficits (67.3% of cases),
      but a low occurrence of definitive morbidity (2.3% of cases). A pattern of
      typical language disturbances related to the phonological and semantic system can
      be identified according to tumor location, with preservation being important for
      the maintenance of language integrity. CONCLUSION: Our study supports the routine
      use of subcortical stimulation for language tract identification as a reliable
      tool for guiding surgical removal of gliomas in or in close proximity to language
      areas or pathways.

PMID- 17228255
TI  - Subependymal giant-cell astrocytomas in pediatric tuberous sclerosis disease:
      when should we operate?
AB  - OBJECTIVE: A small percentage of tuberous sclerosis patients will develop a
      subependymal giant-cell astrocytoma. Given the morbidity and mortality when such
      a lesion is left undiagnosed, successive follow-up imaging in pediatric patients
      has been recommended. Surgical removal of the lesion has become the procedure of
      choice; however, the timing of this surgery is still a controversial subject. By
      analyzing our own series of data, as well as other published series, we have
      attempted to reach a consensus on the benefits of early versus late surgery.
      METHODS: We retrospectively reviewed 19 patients treated surgically for
      intraventricular tumors in Foch Hospital and at the Fondation Adolphe de
      Rothschild in Paris, France, and we analyzed published pediatric reports from
      1980 to 2006. RESULTS: The results from our own population, as well as from other
      published pediatric series (15 series), indicate that subependymal giant-cell
      astrocytomas have a good prognosis when a macroscopically total resection has
      been performed. In our series, residual lesions tended to enlarge, but residual
      tumors remaining stable have been reported. Careful follow-up examination should
      be undertaken because late recurrences do occur. Larger or symptomatic lesions
      tend to have a higher morbidity. CONCLUSION: We think that any lesion fulfilling
      the criteria for a subependymal giant-cell astrocytoma as previously described in
      the literature (lesion around the foramen of Monro, greater than 5 mm, with
      incomplete calcifications) should be removed as soon as clear evidence of growth
      has been confirmed.

PMID- 17228256
TI  - Subarachnoid hemorrhage treated with clipping: long-term effects on employment,
      relationships, personality, and mood.
AB  - OBJECTIVE: Only one-third of patients regain functional independence after
      aneurysmal subarachnoid hemorrhage (SAH). Despite this recovery, many of these
      patients experience psychosocial problems. We assessed the long-term effects of
      SAH on employment, relationships, personality, and mood. METHODS: We included
      patients who had been treated by clipping after SAH between 1985 and 2001 and who
      resumed independent living. Patients underwent structured interviews regarding
      employment, relationships, and personality before and after the SAH. Anxiety and
      depression were assessed by the Hospital Anxiety and Depression Scale, and scores
      were compared between the study group and a control population. RESULTS: Six
      hundred and ten patients were interviewed (mean follow-up after SAH, 8.9 yr). Of
      the employed patients, 26% stopped working and 24% worked shorter hours or had a
      position with less responsibility. On average, patients returned to work 9.4
      months after discharge (range, 0-96 mo). Seven percent of patients were divorced
      because of SAH-related problems. Fifty-nine percent of the patients reported
      changes in personality, with the most commonly noted changes being increased
      irritability (37%) or emotionality (29%). Patients with SAH had a statistically
      significant higher mean depression score than the control population.
      Approximately 10% of the patients had a Hospital Anxiety and Depression Scale
      score in the range of a probable depressive or anxious state. Only 25% reported a
      complete recovery without psychosocial or neurological problems. CONCLUSION: The
      long-term psychosocial effects of SAH are considerable, even in patients who
      regain functional independence. Treating physicians should be aware of these long
      term effects of SAH when discussing prognosis and reintegration to work after
      initial recovery with patients and family.

PMID- 17228257
TI  - Three-day phenytoin prophylaxis is adequate after subarachnoid hemorrhage.
AB  - OBJECTIVE: Phenytoin (PHT) is widely administered after subarachnoid hemorrhage,
      often for several weeks or months. In addition to known side effects, PHT use has
      been correlated with cognitive disability and poor outcome. To reduce the rate of
      PHT complications, we converted from a multi-week prophylactic regimen to a 3-day
      course of treatment. This study evaluates the changes in seizure rates and
      adverse events. METHODS: From July 1998 to June 2002, 453 patients with
      spontaneous subarachnoid hemorrhage were treated. In the first 9 months, 79
      patients were administered PHT until discharged from the hospital, unless a drug
      reaction occurred first. In the last 39 months, PHT was discontinued 3 days after
      admission (370 patients), unless there was a history of epilepsy (four patients).
      This study represents a retrospective analysis of prospectively collected data,
      with follow-up periods of 3 to 12 months after discharge. RESULTS: The 3-day PHT
      regimen produced a statistically significant reduction (P = 0.002) in the rate of
      PHT complications. In the first period, seven (8.8%) out of 79 patients
      experienced a hypersensitivity reaction, compared with two (0.5%) out of 370
      patients in the second period. The percentage of patients having seizures, both
      short- and long-term, did not change significantly. In the first period, the
      seizure rate during hospitalization was 1.3%; in the second period, it was 1.9%
      (P = 0.603). At an average follow-up period of 6.7 months, three (5.7%) out of 53
      survivors in the first period experienced a seizure (including those who had a
      seizure during hospitalization). In the second period, 12 (4.6%) out of 261
      survivors experienced a seizure at an average follow-up period of 5.4 months (P =
      0.573). CONCLUSION: A 3-day regimen of PHT prophylaxis is adequate to prevent
      seizures in subarachnoid hemorrhage patients. Drug reactions are significantly
      reduced, but seizure rates do not change. Short-term PHT administration may be a
      superior treatment paradigm.

PMID- 17228258
TI  - Preoperative simulation for microvascular decompression in patients with
      idiopathic trigeminal neuralgia: visualization with three-dimensional magnetic
      resonance cisternogram and angiogram fusion imaging.
AB  - OBJECTIVE: Precise assessment of the complex nerve-vessel relationship at the
      root entry zone of the trigeminal nerve is useful for planning microvascular
      decompression in patients with idiopathic trigeminal neuralgia. We have applied a
      fusion imaging technique of three-dimensional (3-D) magnetic resonance
      cisternography and co-registered 3-D magnetic resonance angiography (MRA) that
      allows virtual reality for the preoperative simulation of the neurovascular
      conflict at the trigeminal nerve root entry zone. METHODS: Fusion images of 3-D
      magnetic resonance cisternograms and angiograms were reconstructed by a
      perspective volume-rendering algorithm from the volumetric data sets of magnetic
      resonance cisternography, obtained by a T2-weighted 3-D fast spin echo sequence,
      and co-registered MRA, by a 3-D time-of-flight sequence. Consecutive series of 12
      patients with idiopathic trigeminal neuralgia were studied with fusion 3-D
      magnetic resonance cisternogram and MRA in the preoperative assessment for the
      microvascular decompression of the affected trigeminal nerve. RESULTS: The
      complex anatomical relationship of the offending vessels to the trigeminal nerve
      root entry zone was depicted on the fusion 3-D magnetic resonance cisternogram
      and MRA. The presence of offending vessels and compressive site of neurovascular
      conflict was assessed from the various viewpoints within the cistern and was
      presumed by the preoperative simulation through the surgical access (surgeon's
      eye view). The blinded surgical trajectory was discerned by the virtual image
      through the opposite direction projected from above (bird's-eye view). The 3-D
      visualization of the nerve-vessel relationship with fusion images was consistent
      with the intraoperative trajectory and findings. CONCLUSION: Fusion imaging of 3
      D magnetic resonance cisternogram and MRA may prove a useful adjunct for the
      diagnosis and decision-making process to execute the microvascular decompression
      in patients with idiopathic trigeminal neuralgia.

PMID- 17228259
TI  - Cerebral blood flow in traumatic contusions is predominantly reduced after an
      induced acute elevation of cerebral perfusion pressure.
AB  - OBJECTIVE: To evaluate the response to an acute elevation of cerebral perfusion
      pressure (CPP) of the regional cerebral blood flow (rCBF) measured in the
      edematous area of traumatic contusions. METHODS: rCBF was measured in the
      intracontusional low-density area, in the pericontusional healthy-appearing brain
      tissue surrounding the contusion, in a healthy-appearing area in the
      contralateral hemisphere, in 16 head-injured patients with 16 traumatic
      contusions larger than 2 cm at baseline, and after 20 minutes of norepinephrine
      induced 20-mmHg elevation of CPP levels. RESULTS: After an induced acute
      elevation of CPP from baseline values of 65.8 ml/100 g/min (standard deviation,
      8.6) to final values of 88.7 ml/100 g/min (standard deviation, 8.9; P < or =
      0.0001), we found that rCBF mean levels decreased in the intracontusional low
      density area (P = 0.0278), and change in rCBF was inversely associated to the
      baseline values. After grouping contusions according to the rCBF response to
      induced acute CPP elevation, rCBF mean values recorded at baseline were
      significantly lower in lesions with "rCBF improvement" than in those with "rCBF
      reduction" in the intracontusional low-density area (P = 0.0435). CONCLUSION: Our
      findings suggest that CPP elevation induced by norepinephrine is effective in
      improving contusional rCBF only in selected cases, which are represented by a
      subset of contusions with critical perfusion, which can be identified by rCBF
      measurements. Conversely, in contusions with rCBF higher than critical low
      values, the CPP elevation could probably induce a temporary breakdown of the
      blood brain barrier, and the norepinephrine leads to a vasoconstriction with a
      worsening of regional perfusion.

PMID- 17228260
TI  - Is aqueductal stroke volume, measured with cine phase-contrast magnetic resonance
      imaging scans useful in predicting outcome of shunt surgery in suspected normal
      pressure hydrocephalus?
AB  - OBJECTIVE: To evaluate clinical usefulness of cerebrospinal fluid stroke volume
      (SV) assessed in the cerebral aqueduct, via cine phase-contrast magnetic
      resonance imaging, for predicting outcome after shunt surgery in suspected normal
      pressure hydrocephalus. METHODS: Thirty-eight patients with suspected normal
      pressure hydrocephalus were included. SV was assessed using cine phase-contrast
      magnetic resonance imaging, and the results were kept blinded until postoperative
      follow-up after 7 +/- 5.8 months (mean +/- standard deviation). Selection to
      surgery was based on a positive lumbar infusion test or cerebrospinal fluid tap
      test, and outcome was evaluated with objective tests. RESULTS: Six patients were
      excluded from SV measurements because of technical difficulties. Eight patients
      were not operated (negative lumbar infusion test and cerebrospinal fluid tap
      test). SV in the not operated patients (mean, 66 +/- 53 microl) did not differ
      from the operated patients (95 +/- 78 microl; P = 0.335). Operated patients
      showed statistically significant improvements in walk (P = 0.020), reaction time
      (P = 0.006), and memory (P = 0.001) tests. Patients were divided into three
      groups according to SV range: low (0-50 microl), middle (51-100 microl), and high
      (>100 microl). No statistically significant (P > 0.05) improvements in any of the
      objective tests were found in any of the SV ranges. The numbers of individually
      improved patients were similar in the different SV ranges: six out of seven in
      the low, nine out of nine in the middle, and five out of eight in the high range.
      Weak correlations were found between SV and the initial pulse amplitude (Rs =
      0.043; P = 0.014) as well as the plateau pulse amplitude (Rs = 0.043; P = 0.014)
      as measured with the lumbar infusion test. CONCLUSION: The data from this study
      show no evidence that cine phase-contrast magnetic resonance imaging measurements
      of SV in the cerebral aqueduct are useful for selecting patients with normal
      pressure hydrocephalus symptoms to shunt surgery.

PMID- 17228261
TI  - Clinicoradiological review: bilateral ethmoidal artery dural arteriovenous
      fistulas.

PMID- 17228263
TI  - Functional imaging in a low-field, mobile intraoperative magnetic resonance
      scanner: expanded paradigms.
AB  - OBJECTIVE: We previously demonstrated the capability to obtain functional
      magnetic resonance imaging (MRI) scans of the motor cortex in healthy volunteers
      using a low-field mobile operating room-based MRI scanner with 0.12-T field
      strength. Using an expanded (0.15-T), but still mobile, version of this system,
      our goal was to acquire data showing activation of other areas of functionally
      important cortex. METHODS: Five healthy volunteers were scanned with the low
      field scanner using finger tapping, hand touch, silent word generation, text
      listening, and visual stimulation paradigms. The data was analyzed offline using
      publicly available software. For comparison, the volunteers were then scanned
      with a 3-T diagnostic MRI scanner. RESULTS: Significant cortical activation was
      demonstrated on 16 out of 22 images obtained on the operating room-based scanner.
      Motor activation was most robust, followed by silent word generation, text
      listening, and hand touch paradigms. The correlation coefficients compared
      favorably with the images obtained on the 3-T scanner. The signal changes were
      higher for images obtained with the low-field, mobile scanner compared with those
      performed with the 3-T diagnostic MRI scanner. CONCLUSION: Functional MRI scans
      of multiple cortical areas can be acquired with a low-field strength magnet
      designed for intraoperative imaging. Further refinement of this technique may
      allow for the acquisition of true intraoperative functional MRI scans
      immediately, before, and even during cranial surgery in select patients.

PMID- 17228262
TI  - Neural engineering to produce in vitro nerve constructs and neurointerface.
AB  - OBJECTIVE: Recently, our laboratory recapitulated a natural form of axon growth
      that occurs between late embryogenesis and early adulthood. In this article, we
      describe how this novel neural engineering approach may be used to produce a
      nervous tissue interface to integrate disconnected motor and sensory functions
      for external control. METHODS: For nervous system repair, we recently developed a
      unique method to engineer nervous tissue constructs in vitro consisting of
      bundles of axons spanning two populations of neuronal somata. To integrate
      electronics and nervous tissue to transform electrophysiological signals into
      electronic signals, we have designed a nervous tissue interface. RESULTS: Our
      nervous tissue interface consists of stretch-grown nervous tissue with one end
      interfaced with a multiple electrode array, enabling us to detect and record real
      time efferent signals conducted down the nerve and stimulate afferent sensory
      signaling. CONCLUSION: Our ultimate goal is to develop a neurally controlled
      prosthesis and a nervous system interface that could be linked to the patient's
      thoughts, providing two-way signaling for motor control and feedback from
      multiple external stimuli.

PMID- 17228264
TI  - Genetic aberrations in gliomatosis cerebri.
AB  - OBJECTIVE: Identifying the genetic alterations in gliomatosis cerebri (GC) may
      yield clinically useful prognostic markers and provide clues as to whether GC
      represents a distinct pathological entity or is an extreme form of diffusely
      infiltrative glioma. METHODS: Clinical histories, treatment histories, magnetic
      resonance imaging, and pathological analysis of patients with GC treated at
      either the University of California San Francisco or the Mayo Clinic were
      reviewed. Degenerate oligonucleotide-primed polymerase chain reaction was
      performed on biopsy samples of GC. Comparative genomic hybridization was used to
      determine relative deoxyribonucleic acid copy number. We evaluated relationships
      of clinical and radiological treatment and comparative genomic hybridization data
      to survival after diagnosis with Cox regression analysis. RESULTS: Radiographic
      analysis and biopsy specimens were available for study in 29 patients (17 men, 12
      women). Comparative genomic hybridization was successfully performed in 22
      patients. Contrast enhancement was the most significant predictor of poor
      survival (P = 0.0026). Loss of chromosomes 13q and 10q and gains of 7q were also
      independent significant predictors of poor survival (P = 0.0032, 0.0335, and
      0.0487, respectively). Patients treated with temozolomide or with radiation
      therapy had improved survival, but this effect did not reach statistical
      significance (P = 0.180 and 0.124, respectively). CONCLUSION: Chromosomal
      aberrations associated with aggressive astrocytomas are predictors of poor
      outcome in patients with GC. This suggests that GC may be an architectural
      variant of diffuse astrocytomas. The presence of these aberrations and the
      presence of any contrast enhancement on magnetic resonance imaging scans are
      possible stratifiers for patients with GC. Stratification of GC into higher- and
      lower-grade forms may be useful in tailoring treatments to patients with this
      disease.

PMID- 17228265
TI  - Microglia in gemistocytic astrocytomas.
AB  - OBJECTIVE: Although gemistocytic astrocytomas are graded as World Health
      Organization II astrocytomas, they behave more aggressively than other
      astrocytomas. Their proliferative potential is low, and it remains an intriguing
      question why these tumors are so biologically "successful." They show a high
      mutation rate of the P53 gene, cytological abnormalities, and frequent
      perivascular mononuclear infiltrates. Microglial cells, a feature of this
      astrocytoma variant, are of increasing interest in the context of glioma growth.
      METHODS: We selected 23 tumor biopsies from 201 samples obtained from patients
      with gemistocytic astrocytomas operated at Mayo Clinic between 1985 and 1998.
      These tumors were formerly analyzed for P53 mutations, p53 protein, and
      proliferative activity (). Immunolabeling for three microglial markers, including
      CR3/43, Ki-M1P, and iba1, was performed on adjacent tissue sections. In addition,
      in situ hybridization for the alpha-chain of the major histocompatibility complex
      (MHC) Class II molecule recognized by the CR3/43 monoclonal antibody was
      performed. RESULTS: A high number of microglia was detected in gemistocytic
      astrocytomas. More microglia were present if the fraction of gemistocytic tumor
      cells was high (correlation coefficient = 0.699; P < 0.0002). Interestingly, a
      number of gemistocytes were immunoreactive for MHC Class II molecules, an
      observation confirmed by in situ hybridization. Importantly, the higher the
      number of Class II immunoreactive gemistocytes, the fewer Class II positive
      microglial cells could be detected (correlation coefficient = -0.5649; P <
      0.005). CONCLUSION: Our results support the view that gemistocytic astrocytomas
      contain unusually high numbers of microglial cells. We propose that the finding
      of aberrant MHC Class II expression by gemistocytic tumor cells correlates with a
      loss of immune-competent MHC Class II-expressing microglia. This may be related
      to the especially poor prognosis of gemistocytic astrocytomas for which induction
      of T cell anergy could provide one explanation.

PMID- 17228267
TI  - Persistence of the nitric oxide-dependent vasodilator pathway of cerebral vessels
      after experimental subarachnoid hemorrhage.
AB  - OBJECTIVE: Efficiency of the treatment of cerebral vasospasm (CVS) after
      subarachnoid hemorrhage (SAH) by interfering with the nitric oxide-cyclic
      guanosine monophospate (cGMP) pathway seems to be inconsistent. So far, it
      remains unclear whether or not insufficient access to the drugs or impaired
      reactivity of the vessels is responsible for this inconsistency. Therefore, the
      aim of the present investigation was to characterize this pathway on cerebral
      arteries during CVS. METHODS: CVS was induced using the rat double hemorrhage
      model and was determined by magnetic resonance perfusion weighted imaging. Rats
      were sacrificed on Day 3 and Day 5 after SAH. Immunohistochemical staining of the
      basilar artery for endothelial nitric oxide synthases and the alpha- and beta
      subunits of the soluble guanylate cyclase was performed. Basilar artery ring
      segments on Day 5 were used for measurement of isometric force. Concentration
      effect curves for acetylcholine, sodium nitroprusside, and 8-bromo-cGMP were
      constructed and compared by maximum effect and pD2. RESULTS: The
      immunohistochemical expression of endothelial nitric oxide synthase was
      comparable in all groups. The soluble guanylate cyclase alpha- and beta-subunits
      were significantly diminished on Day 3, but recovered by Day 5. The relaxation
      attributable to acetylcholine and 8-bromo-cGMP was virtually identical in
      controls and during CVS. Relaxation attributable to sodium nitroprusside,
      however, was significantly enhanced after SAH (maximum effect, control: 88 +/-
      12%; Day 5: 117 +/- 26%). CONCLUSION: The present investigations suggest the
      persistence of endothelium-, nitric oxide-, and cGMP-dependent relaxation during
      CVS. Therefore, the treatment of CVS interfering with this pathway seems not to
      be limited by alterations inside the vessel wall.

PMID- 17228268
TI  - High-frequency monopolar electrical stimulation of the rat cerebral cortex.
AB  - OBJECTIVE: Intraoperative monitoring of the motor-evoked potential has been
      widely used in patients undergoing neurosurgery. Direct stimulation of the brain
      with high-frequency monopolar stimulation (HFMS) is one of the most common
      methods to produce motor-evoked potential. We studied the influence of HFMS on
      the rat cerebral cortex. METHODS: We applied 1.5, 15, 30, 40, or 50 mA of HFMS to
      the rat sensorimotor cortex by a short sequence of five monopolar, monophasic,
      anodal rectangular 500-Hz pulses. We delivered one short five-pulse train 100
      times every 5 seconds and examined pre- and post-stimulation
      electroencephalograms and histological changes at the stimulation site. RESULTS:
      We observed no spike waves after HFMS in any of the rats. There was no change in
      the power spectrum or frequency content in any of the rats exposed to HFMS.
      Histologically, there was significant swelling of the dendrites in rats
      sacrificed immediately after exposure to 40- and 50-mA stimulation; the 50-mA
      stimulation group also exhibited slight swelling of the mitochondria. These
      findings were not obtained in any of the rats sacrificed 30 days after
      stimulation. CONCLUSION: In rats exposed to a stimulation intensity of 30-mA or
      less, no morphological or electrophysiological changes were observed. However,
      the possibility that HFMS may affect neural tissue cannot be ruled out.

PMID- 17228266
TI  - Adenoviral-mediated gene transfer into the canine brain in vivo.
AB  - OBJECTIVE: Glioblastoma multiforme (GBM) is a devastating brain tumor for which
      there is no cure. Adenoviral-mediated transfer of conditional cytotoxic (herpes
      simplex virus [HSV] 1-derived thymidine kinase [TK]) and immunostimulatory (Fms
      like tyrosine kinase 3 ligand [Flt3L]) transgenes elicited immune-mediated long
      term survival in a syngeneic intracranial GBM model in rodents. However, the lack
      of a large GBM animal model makes it difficult to predict the outcome of
      therapies in humans. Dogs develop spontaneous GBM that closely resemble the human
      disease; therefore, they constitute an excellent large animal model. We assayed
      the transduction efficiency of adenoviral vectors (Ads) encoding beta
      galactosidase (betaGal), TK, and Flt3L in J3T dog GBM cells in vitro and in the
      dog brain in vivo. METHODS: J3T cells were infected with Ads (30 plaque-forming
      units/cell; 72 h) encoding betaGal (Ad-betaGal), TK (Ad-TK), or Flt3L (Ad-Flt3L).
      We determined transgene expression by immunocytochemistry, betaGal activity,
      Flt3L enzyme-linked immunosorbent assay, and TK-induced cell death. Ads were also
      injected intracranially into the parietal cortex of healthy dogs. We determined
      cell-type specific transgene expression and immune cell infiltration. RESULTS:
      Adenoviral-mediated gene transfer of HSV1-TK, Flt3L, and betaGal was detected in
      dog glioma cells in vitro (45% transduction efficiency) and in the dog brain in
      vivo (10-mm area transduced surrounding each injection site). T cells and
      macrophages/activated microglia infiltrated the injection sites. Importantly, no
      adverse clinical or neuropathological side effects were observed. CONCLUSION: We
      demonstrate effective adenoviral-mediated gene transfer into the brain of dogs in
      vivo and support the use of these vectors to develop an efficacy trial for canine
      GBM as a prelude to human trials.

PMID- 17228269
TI  - Dittmar and the history of stereotaxy; or rats, rabbits, and references.
AB  - The renaissance of stereotactic functional neurosurgery has resulted in increased
      interest in its origins. Twenty articles concerning this field trace the history
      back to a paper published in 1873 by Dittmar: "Uber die Lage des sogenannten
      Gefaesszentrums in der Medulla oblongata" [On the location of the so-called
      vasomotor center in the medulla oblongata]. Few facts are presented. But, taken
      together, the impression given by the secondary sources is that Dittmar, in 1873,
      presented a guiding device for localization of intracranial structures for the
      positioning of electrodes/blades in the medulla oblongata in rats. Of the
      publications that cite Dittmar's original article as their only quoted source,
      half did not specify the inserted object and the animal of the experiment. The
      remaining articles reported either that the introduced object was an electrode or
      that the experiments were performed on rats. Dittmar's original article, however,
      did not report use of his apparatus for insertion of electrodes, nor did he use
      rats. All experiments were performed by making incisions in the medulla oblongata
      in rabbits. Dittmar's apparatus was constructed to allow more precision when
      performing incisions in the medulla oblongata than could be obtained performing
      incisions freehand. The incision point was chosen and the blade introduced with
      direct visual guidance. This has been described as "spatial localization of
      intracranial structures," "a special targeting instrument," or simply, "a guiding
      device." In our opinion, it can most properly be classified as a supportive arm.

PMID- 17228270
TI  - Future perspectives on antithrombin and antiplatelet therapies: novel
      antiplatelet and antithrombin therapies.
AB  - The recognition that thrombosis is fundamental to acute coronary syndromes (ACS)
      has inspired the development of novel therapies to inhibit platelet aggregation
      and thrombus formation. Several recent advances have been made in the management
      of patients undergoing percutaneous coronary revascularization and those with
      acute coronary syndromes to improve early and late clinical outcomes. The
      research efforts leading to these improvements in care have focused on
      antiplatelet and anticoagulant therapies coupled with early invasive treatment
      options. In particular, ongoing clinical trials seek to refine treatment
      strategies for patients relative to individual risk presentation and to determine
      the appropriate timing of the administration of antithrombotic therapies and
      revascularization. Simultaneous with attention toward improving efficacy with
      novel antithrombotic therapies, however, is an ongoing need to minimize bleeding
      risk. The purpose of this review is to provide a pathophysiologic rationale for
      the development of novel antiplatelet and antithrombin therapies in ACS and
      percutaneous coronary intervention, to examine the results of recent trials, and
      to present future directions for clinical investigation.

PMID- 17228273
TI  - Benefit of sentinel lymph node mapping in non-small cell lung cancer.

PMID- 17228274
TI  - Thoracoscopic surgery for lung cancer.
AB  - Thoracoscopic surgery has raised awareness in minimizing invasiveness in
      respiratory surgery. In the case of lung cancer, technical difficulties
      associated with standard curative surgery may not allow the use of a total
      thoracoscopic procedure. Although thoracoscopic lung cancer surgery is minimally
      invasive and safe, it demands a high level of skill and care. Surgery is often
      performed using a small incision and direct vision, with the thoracoscope serving
      as a light source. However, thoracoscopic surgery is expected to progress further
      in the near future. In addition, a new surgical system that comprehends both open
      and video-assisted thoracic surgery (VATS) may gain popularity.

PMID- 17228275
TI  - Role of video-assisted thoracic surgery for the diagnosis of indeterminate
      pulmonary nodule.
AB  - PURPOSE: A study was undertaken to evaluate the validity and efficacy of video
      assisted thoracic surgery (VATS) for the diagnosis of indeterminate pulmonary
      nodules. MATERIALS AND METHODS: Between April 2001 and November 2004, 57 adult
      patients (31 males, 26 females) with a clinical diagnosis of pulmonary nodules by
      preoperative chest computed tomographic (CT) scanning were included in this
      study. RESULTS: A definitive tissue diagnosis was obtained in all 57 patients.
      The mean age of the patients was 66+/-9.8 yrs. The mean size of the tumor was
      1.76+/-0.67 cm. 38 patients (67%) had malignant disease. Twenty eight patients
      (49%) had primary lung cancer and 10 patients (18%) had metastatic lung cancer
      from an extrathoracic primary neoplasm. The rate of malignancy was 65% in the
      tumor sizes equal to or less than 2 cm. Among primary lung cancer, most patients
      had primary adenocarcinoma (24 cases)(86%). Pathologic staging showed T1N0 (stage
      IA) in 18 cases (69%), T2N0 (stage IB) in 4 cases (15%), T2N1 (stage IIB) in 1
      case (4%), and T1N2 (stage IIIA) in 3 cases (12%). In 10 patients (18%) who
      required preoperative placement of a localization hookwire with a string near the
      nodule, the rate of malignancy was 70%. In 7 patients with positive positron
      emission tomography (PET) imaging with F-18 fluorodeoxyglucose (FDG), the rate of
      malignancy was 57% and proved to be falsely positive in 3 cases (43%). There was
      no operative mortality and no significant morbidity in all cases. CONCLUSION: We
      proposed that VATS, which is safe and offers virtually 100% sensitivity and
      specificity, should be performed for most small (<3 cm in diameter) and all
      indeterminate pulmonary lesions on the basis of these results.

PMID- 17228276
TI  - Is oxygen supplementation needed after standard pulmonary resection for primary
      lung cancer?
AB  - OBJECTIVE: Theoretically, anatomical pulmonary resection does not cause any shunt
      effect, and thus it is thought that oxygen (O(2)) supplementation is not
      necessary after a pulmonary lobectomy or pneumonectomy. Without O(2)
      supplementation, we have streamlined our postoperative management for pulmonary
      resection. In the present study, we prospectively assessed our perioperative
      management for both requirement of O(2) supplementation and postoperative
      complications. PATIENTS AND METHODS: From April 2003 to March 2005, 89
      consecutive patients underwent a pulmonary lobectomy or pneumonectomy for primary
      lung cancer. Our protocol for perioperative care is as follows: [Preoperative]
      Smoking cessation longer than 2 weeks before surgery. [Intraoperative] Postero
      lateral thoracotomy through the 5th or 6th rib bed. Cutting of the 5th or 6th
      intercostal nerve before closure of the wound. [Postoperative day (POD) 1] O(2)
      administration was discontinued in the morning. Ambulation without O(2)
      supplementation. [POD 2] Removal of an epidural catheter. During the
      postoperative period, percutaneous monitoring of O(2) saturation was continued.
      RESULTS: The mean postoperative O(2) saturation of those 89 patients was 97.0% on
      the POD 1, 96.4% on the POD 2, 96.6% on the POD 3, and 97.5% on the POD 7. Only 3
      patients required O(2) therapy after discontinuation of O(2) administration due
      to non-lethal pulmonary embolism. Depending on the duration of smoking cessation
      prior to operation, the patients were divided into 4 groups (2 weeks >, 1 month
      >, 1 month </=, and nonsmokers). Neither the incidence of postoperative
      complications nor the length of postoperative hospital stay was different among
      those 4 groups. CONCLUSION: It is suggested that the postoperative O(2)
      supplementation is not routinely necessary.

PMID- 17228277
TI  - Limitations of retrograde continuous tepid blood cardioplegia for myocardial
      remodeling.
AB  - OBJECTIVE: We assessed potential limitations of retrograde continuous tepid blood
      cardioplegia (RCTBC) for myocardial remodeling, represented by hypertrophied
      and/or dilated myocardium in patients with severe cardiomyopathy following single
      aortic valve replacement. METHODS: The study was conducted on 91 patients who
      underwent initial single aortic valve replacement with tepid cardiopulmonary
      bypass (CPB) and RCTBC. Based on the postoperative maximum creatine phosphokinase
      (max CPK)-MB level, the patients were allocated to Group H (>/=100 IU/mL) with
      severe cardiomyopathy or Group L (<100 IU/mL) to make intergroup comparisons of
      preoperative, intraoperative, and postoperative parameter values. RESULTS:
      Preoperative measurements were as follows: pressure gradient between left
      ventricle and aorta (DeltaPG), 92.8+/-46.2 mmHg in Group H and 57.9+/-41.6 mmHg
      in Group L (p<0.01); implanted valve size, 21.0+/-2.2 mm in Group H and 22.8+/
      2.2 mm in Group L (p<0.01); left ventricular end-diastolic volume (LVEDV),
      155.7+/-73.3 mL in Group H and 224.3+/-101.5 mL in Group L (p<0.01). The rate of
      RCTBC flow rate increase did not differ between the groups (17.6% in Group H and
      20.7% in Group L), while the rate of concomitant use of optional antegrade
      coronary perfusion was significantly lower in Group H (25%) than in Group L (37%)
      (p<0.05). Pre- and post-perfusion lactic acid levels in the myocardial protection
      solution measured every 30 min after aortic cross clamping were higher in Group H
      than in Group L. CONCLUSION: The study suggests preoperative high DeltaPG, small
      aortic root diameter, and low LVEDV, namely, concentrically hypertrophied
      myocardium, as risk factors for severe cardiomyopathy after RCTBC. RCTBC in
      patients with any risk factor should be accompanied by an increase in initial
      continuous perfusion flow and/or aggressive use of intermittent antegrade
      coronary perfusion.

PMID- 17228278
TI  - Central arterial cannulation and the arch first method for aortic arch aneurysm
      repair.
AB  - BACKGROUND: We investigated whether the axillary artery or ascending aorta
      cannulation combined with the arch first method decreases the risk of stroke
      during total arch replacement. PATIENTS AND METHODS: From January 2002 to January
      2006, 35 total arch replacements were performed with the arch first method and
      central arterial cannulation. The mean age was 66+/-10 years. The cannulation
      sites were the axillary artery in 19 and the ascending aorta in 16. The arch
      first method (a short period of deep hypothermic circulatory arrest with
      retrograde cerebral perfusion and then subsequent antegrade cerebral perfusion)
      was used in all patients. RESULTS: The mean retrograde cerebral perfusion time
      was 29+/-7 min. The incidence of the permanent neurological dysfunction related
      to the surgical procedures was 2.9% (1/35). Hospital mortality was 5.7% of
      patients (2/35). There was no difference in the operative outcome between the 2
      arterial inflow sites. CONCLUSION: At the time of total arch replacement, the use
      of central arterial cannulation and the arch first method are effective methods
      for preventing permanent brain injury. Cannulation of the ascending aortic using
      Dispersion cannula perfusing toward the aortic valve is considered to be a safe
      and favorable method for central arterial cannulation.

PMID- 17228279
TI  - Simplified elephant trunk technique promotes thrombo-occlusion of the false lumen
      in acute type A aortic dissection.
AB  - OBJECTIVE: We developed a "simplified elephant trunk (SET) graft technique" as a
      refinement of the original elephant trunk. A cuff is created in a single 4
      branched graft, which is used for the distal anastomosis; the residual distal
      graft is used as the trunk. We expected the SET would secure the anastomosis and
      promote the thrombo-occlusion of the false lumen in the down stream of the aorta.
      In this paper, we highlight the usage of the SET for arch replacement of acute
      aortic dissection cases in comparison with the same arch replacement without the
      SET method. PATIENTS AND METHODS: Between March 1996 and March 2002, 35 patients
      underwent arch replacement for acute aortic dissection. Twenty-two of them had a
      patent false lumen in the downstream aorta at the operation and 17 (SET: 8, non
      SET (NSET) : 9) out of 22 underwent enhanced computed tomography (CT) scan 2
      weeks after and 1 year after operation. We calculated the ratio of the false
      lumen in the aorta (F ratio) and the ratio of the patent false lumen in the whole
      false lumen (E ratio) by CT scan. These values were calculated every 3 cm down to
      15 cm below the anastomosis, thus resulting in 5 segments. RESULTS: The false
      lumen throughout all segments disappeared (F ratio =0) in none of both group 2
      weeks after operation. One year thereafter, in 5 (63%) patients in the SET group,
      no false lumen in any segment existed, while in contrast a false lumen still
      existed in some of the segments in all NSET patients. Although neither the F and
      E ratio of the NSET group change during this period in any segments, those of the
      SET group decreased significantly in all the segments except for the E ratio of
      segment 5. CONCLUSION: The SET promoted thrombo-occlusion thus leading to the
      disappearance of the residual false lumen, possibly by avoiding persistent
      endoleakage at the anastomotic site.

PMID- 17228280
TI  - Pulmonary torsion following right upper lobectomy.
AB  - We report on a case of postoperative lobar torsion in a 51-year-old woman
      following right upper lobectomy. A right middle lobar torsion was diagnosed by
      postoperative observation with chest X-ray and bronchofiberscopy. An emergency
      rethoracotomy was performed and a middle lobectomy was carried out. The
      postoperative course was uneventful and the patient was discharged on the 17th
      day after rethoracotomy. Careful postoperative observation with chest radiography
      and bronchofiberscopy is important for the precise diagnosis of a lobar torsion.
      In a case of lobar torsion following lobectomy, rethoracotomy should be
      immediately carried out.

PMID- 17228281
TI  - A subtotal sternectomy successfully reconstructed with composix mesh.
AB  - Sternal tumors are uncommon, which often require extended resections with
      reconstructions. Various techniques have been used, including a choice of
      prostheses and the use of musculocutaneous flaps for reconstructions. A 74-year
      old male presented with a metastatic sternal tumor. He underwent a subtotal
      sternectomy with partial resection of bilateral clavicles and ribs. A sternal
      reconstruction was performed with Composix mesh and pectoralis major (PM) muscle
      flaps. This prosthesis was thought to be very suitable due to the ease of
      handling, good stability, and prevention of adhesion. In comparison to
      conventional prostheses, these points could be advantageous.

PMID- 17228282
TI  - Giant mediastinal liposarcoma: a case report.
AB  - Liposarcomas are extremely rare in the mediastinum. They may achieve considerable
      size before causing any symptoms. Mediastinal liposarcomas may invade surrounding
      structures like the pericardium or the superior vena cava. Complete surgical
      excision is the optimal treatment in resectable cases. Excision of adjacent
      structures like the pericardium may be needed if the tumor infiltrates them. We
      report on a case of a giant liposarcoma of the mediastinum involving both
      hemithoraces and extending into the neck, which was successfully managed by
      complete surgical excision.

PMID- 17228283
TI  - Delayed hemopericardium with constrictive pericarditis after blunt trauma: a
      report of a surgical case.
AB  - Constrictive pericarditis (CP) following hemopericardium has been reported in the
      literature but its pathogenesis is open to question. Proposed mechanisms include
      trauma leading to damage of the mesothelial lining resulting in decreased
      fibrinolytic activity in the presence of blood. We present a patient who
      sustained blunt thoracoabdominal trauma in a car accident and subsequently
      developed delayed hemopericardium leading to constrictive pericarditis and
      impending cardiac tamponade. We performed a pericardiectomy to relieve the
      compression. Closely prolonged monitoring and emergent operation are suggested
      for such kinds of delayed complications.

PMID- 17228284
TI  - Off-pump coronary artery bypass grafting for a patient with anomalous origin of
      the right coronary artery from the pulmonary artery.
AB  - We report on a case of a 70-year-old chronic hemodialysis patient. He presented
      with anomalous origin of the right coronary artery from the pulmonary artery
      (ARCAPA) and severe left anterior descending coronary artery (LAD) stenosis,
      which supplied collateral flow to the right coronary artery (RCA). The patient
      complained of myocardial ischemic symptoms during routine hemodialysis. We
      performed off-pump coronary artery bypass grafting (OPCABG) surgery and ligation
      of the origin of the ARCAPA. Previous reports described that the myocardial
      ischemia was a rare complication with the ARCAPA patients. However, this case
      required coronary revascularization because of the atherosclerotic LAD stenosis
      as a collateral source of the RCA.

PMID- 17228285
TI  - Large saphenous vein graft aneurysm with a fistula to the right atrium.
AB  - We report on a case of a 65-year-old man who was admitted for anterior chest pain
      on effort. He had received coronary artery bypass grafting (CABG) surgery 20
      years ago with saphenous vein grafts (SVGs) to the left anterior descending
      artery (LAD) and right coronary artery (RCA). An angiography demonstrated large
      aneurysmal dilatation of both grafts and a fistulous communication between the
      middle portion of the right SVG and the right atrium (RA). The aneurysm was
      excised surgically, and the fistula was closed with the right atrial wall with
      additional bypass grafts of the left internal thoracic artery (LITA) and
      gastroepiploic artery (GEA).

PMID- 17228286
TI  - Rupture of a normal-sized, non-dissected distal aortic arch in a Marfan patient.
AB  - We successfully repaired a rupture of a normal-sized, non-dissected distal aortic
      arch in a patient with Marfan syndrome. Six years previously she had undergone
      repair of the thoraco-abdominal aortic aneurysm with a 24-mm knitted Dacron graft
      for type B chronic aortic dissection. The rupture site was located at the back of
      the native distal aortic arch just 10 mm above the proximal anastomosis, and just
      below the left subclavian artery. This unexpected situation might be related to
      dilatation of the knitted Dacron graft up to 34 mm (142%), thus stretching out
      the fragile native aorta in this Marfan patient.

PMID- 17228287
TI  - Late-term regression of stenosis at the kink site in the internal thoracic artery
      in two cases.
AB  - A kink in the internal thoracic artery (ITA) is a rare postoperative complication
      after coronary artery bypass surgery. The kink can be accompanied by significant
      stenosis and has been observed after the ITAs are harvested by the
      skeletonization method. In this report, we present two cases in which early
      postoperative angiography showed the kink accompanied by significant stenosis,
      and late angiography revealed regression of stenosis at the kink site. Immediate
      intervention is not always necessary even when the kink, accompanied by
      significant stenosis was observed on early postoperative angiography.

PMID- 17228288
TI  - A case report on a full-thickness chest wall reconstruction with polypropylene
      mesh and stainless steel mesh concurrently using a transverse rectus abdominis
      myocutaneous flap.
AB  - A full-thickness chest wall resection requires subsequent chest wall
      reconstruction. A chest wall resection and reconstruction was performed using a
      transverse rectus abdominis myocutaneous (TRAM) flap, together with polypropylene
      mesh (Marlex mesh) and stainless steel mesh (SSM). A 71-year-old man was
      diagnosed as having recurrent lung cancer in the chest wall, and underwent
      surgical resection. Marlex mesh was sutured to the posterior wall of the surgical
      defect. A portion of the SSM was adjusted to the size of the defect and cut out.
      Its edges were folded to make the portion into a plate. This SSM plate was placed
      anteriorly to the Marlex mesh and sutured to the ribs. The Marlex mesh was folded
      back on the SSM plate by 2 cm and fixed. After the above procedures, a left-sided
      TRAM flap was raised through a subcutaneous tunnel up to the defect and sutured
      to the region. The patient was discharged from hospital 19 days postoperatively.
      The wound was fine and he had no flail chest or dyspnea, and carcinomatous pain
      resolved.

PMID- 17228289
TI  - Is quality of anticoagulation a 'wild card' in the treatment of patients with
      atrial fibrillation?

PMID- 17228290
TI  - Should all patients with heart failure and left ventricular dysfunction receive
      combined CRT-ICD therapy?

PMID- 17228291
TI  - Can Helicobacter pylori eradication therapy be shortened to 4 days?

PMID- 17228292
TI  - How useful is exercise and dietary counseling after liver transplantation?

PMID- 17228293
TI  - Is epalrestat an effective treatment for diabetic peripheral neuropathy?

PMID- 17228294
TI  - What factors determine patient adherence to osteoporosis treatment regimens?

PMID- 17228295
TI  - Renal hemodynamic responses to renin-angiotensin blockade differ in men and
      women.

PMID- 17228296
TI  - Sleep apnea in peritoneal dialysis: nocturnal versus continuous ambulatory
      treatment.

PMID- 17228301
TI  - Epidermolysis bullosa: from fundamental molecular biology to clinical therapies.

PMID- 17228302
TI  - Oct-4: the almighty POUripotent regulator?
AB  - Oct-4 plays an essential role as a central regulator of the undifferentiated
      state. Grinnell et al. demonstrate for the first time that Oct-4 by itself has
      the ability to reprogram committed somatic cells, inducing their
      dedifferentiation by reverting them to a more developmentally potent state. This
      study provides evidence that Oct-4 might be the master regulator of the
      pluripotent state in mammalian cells.

PMID- 17228303
TI  - Human keratinocyte Toll-like receptors promote distinct immune responses.
AB  - It has been well established that Toll-like receptors (TLRs) are expressed by
      keratinocytes and respond to their respective ligands to initiate immune
      responses. However, it appears that keratinocytes, via differential activation of
      TLRs, may play a key role in determining the type of subsequent cutaneous immune
      response generated against a particular pathogen.

PMID- 17228304
TI  - What is the alpha2beta1 integrin doing in the epidermis?
AB  - The alpha2beta1 integrin is abundantly expressed by basal keratinocytes in intact
      skin and is required for re-epithelialization of human skin wounds. However, as
      Grenache et al. and Zweers et al. report, closure of mouse wounds does not
      require this receptor. The discrepancies between these models may reflect
      differences in the composition of the dermal matrices and in the proteinases
      expressed in response to injury.

PMID- 17228305
TI  - Migraine and cardiovascular disease: is there a link?

PMID- 17228306
TI  - Does deep brain stimulation of the subthalamic nucleus in Parkinson's disease
      affect cognition and behavior?

PMID- 17228307
TI  - Should patients with anaplastic oligodendroglial tumors receive adjuvant
      chemotherapy?

PMID- 17228308
TI  - What radiation dose is safe in patients with non-small-cell lung cancer?

PMID- 17228309
TI  - Self-reporting instruments in rheumatoid arthritis.

PMID- 17228310
TI  - Etanercept plus sulfasalazine: added value in rheumatoid arthritis?

PMID- 17228311
TI  - What is the best treatment modality for children with renal stones of 1-2 cm
      diameter?

PMID- 17228312
TI  - Does radical prostatectomy provide a survival benefit as primary treatment for
      high-grade prostate cancer?

PMID- 17228313
TI  - Macrophage-mediated bystander effect triggered by tumor cell apoptosis.
AB  - Restoration of apoptosis is an important therapeutic strategy for cancer, but
      bystander effects may be crucial to treatment success. We examined the
      involvement of bystander effects in the outcome of pro-apoptotic treatments and
      investigated the role of macrophages. Using a murine N202 breast cancer chamber
      model and intravital microscopy, we observed bystander apoptosis in vivo in mixed
      spheroids consisting of bystander N202 cells plus modified N202 cells
      overexpressing the p14ARF N-terminal region, which promotes p53-mediated
      apoptosis. The effect was not observed in cocultures in vitro, and could not be
      transferred through conditioned medium from modified N202 cells. However, if
      macrophages were also included in the N202 co-cultures, bystander apoptosis was
      restored, and correlated with elevated surface expression of phosphatidyl serine,
      a macrophage recognition molecule, on the modified N202 cells. Bystander killing
      was not observed in cocultures of N202 cells plus macrophages plus cisplatin
      treated or 5-fluorouracil-treated N202 cells, where apoptosis induction in the
      target cell population was inefficient, suggesting that specific activation of
      macrophages by apoptotic tumor cells was required. The results suggest that pro
      apoptotic therapies benefit both from the intrinsic vulnerability of cancer cells
      to apoptosis and from an innate immune response that amplifies the therapeutic
      effect.

PMID- 17228314
TI  - A CD46-binding chimpanzee adenovirus vector as a vaccine carrier.
AB  - A replication-defective chimeric vector based on the chimpanzee adenovirus
      serotype C1 was developed and tested as a vaccine carrier in mice. The AdC1 virus
      is closely related to human adenoviruses of subgroup B2 and uses CD46 for cell
      attachment. To overcome poor growth of E1-deleted AdC1 vectors on cell lines that
      provide the E1 of adenovirus of the human serotype 5 (AdHu5) virus in trans, the
      inverted terminal repeats and some of the early genes of AdC1 were replaced with
      those from AdC5, a chimpanzee origin adenovirus of subfamily E. The chimeric
      AdC1/C5 vector efficiently transduces CD46-expressing mouse dendritic cells (DCs)
      in vitro and initiates their maturation. Transduction of DCs in vivo is
      inefficient in CD46 transgenic mice. The AdC1/C5 vector induces transgene product
      specific B- and CD8(+) T-cell responses in mice. Responses are slightly higher in
      wild-type mice than in CD46 transgenic mice. Transgene product-specific T-cell
      responses elicited by the AdC1/C5 vector can be increased by priming or boosting
      with a heterologous adenovirus vector. Pre-existing immunity to adenovirus of the
      common human serotype 5 does not affect induction of cell-mediated immune
      responses by the AdC1/C5 vector. This vector provides an additional tool in a
      repertoire of adenovirus-based vaccine vectors.

PMID- 17228315
TI  - Multiple reduced-intensity conditioning regimens facilitate correction of Fabry
      mice after transplantation of transduced cells.
AB  - Hematopoietic cell transplantation can impact lysosomal storage disorders (LSDs)
      and will be enhanced by gene therapy. Transduced cells in LSDs often secrete the
      therapeutic hydrolase, which can be used by bystander cells. However, toxicity
      associated with myeloablative transplant preparative regimens limits many
      applications of this approach in gene therapy. We hypothesized that reduced
      intensity (RI) conditioning regimens would allow stable engraftment of
      therapeutically transduced cells and allow correction of Fabry disease. We
      transplanted transduced cells into Fabry mice receiving eight different
      clinically relevant chemotherapy- and/or radiotherapy-based RI conditioning
      regimens generating modest and transient lymphoid/myeloid cell depletion. Two
      comprehensive transplantation Protocols were performed. Firstly, transplantation
      of 0.38 x 10(6) gene-modified stem/progenitor cells was nominally effective; none
      of the RI regimens led to stable alpha-galactosidase A (alpha-gal A) correction.
      Secondly, transduced cells were preselected for functional transgene expression
      and transplanted at a higher dose (0.72 x 10(6) cells). Each RI regimen yielded
      engraftment of functional transgene-positive cells through 180 days along with
      increased plasma alpha-gal A activity. Importantly, the RI regimens mediated
      broad organ enzyme correction and were not associated with immune responses
      against alpha-gal A. RI conditioning thus has an important role in gene therapy
      for LSDs; a variety of regimens can be effective in this context.

PMID- 17228316
TI  - Five-year follow-up of trial of replication-competent adenovirus-mediated suicide
      gene therapy for treatment of prostate cancer.
AB  - Replication-competent adenovirus-mediated suicide gene therapy is an
      investigational cancer treatment that combines the oncolytic actions of human
      adenoviruses with the cytotoxic effects of chemo-radiosensitizing genes.
      Previously, we reported the short-term effects of this therapy in men with local
      recurrence of prostate cancer after definitive radiotherapy. With a median
      prostate-specific antigen (PSA) follow-up of 5 years, we report here the effect
      of the gene therapy on prostate-specific antigen doubling time (PSADT), a
      surrogate end point with significant prognostic power. When considering all
      evaluable subjects, the PSADT increased following the gene therapy from a mean of
      17 to 31 months (median 16 to 22 months) (P=0.014). Assuming that salvage
      androgen suppression therapy androgen suppression therapy (AST) was uniformly
      initiated at a PSA of 15 ng/mL, the gene therapy would have delayed the projected
      onset of salvage therapy by an average of 2 years. The results indicate that
      replication-competent adenovirus-mediated suicide gene therapy may provide a
      potential long-term benefit to patients, as shown by a lengthening of the PSADT,
      and delay in when salvage therapy is indicated. Given the high morbidity
      associated with AST, we believe this approach could provide an attractive
      treatment option for selection of patients experiencing PSA relapse following
      definitive therapy.

PMID- 17228317
TI  - The genetic engineering of hematopoietic stem cells: the rise of lentiviral
      vectors, the conundrum of the ltr, and the promise of lineage-restricted vectors.
AB  - Recent studies on the integration patterns of different categories of retroviral
      vectors, the genotoxicity of long-terminal repeats (LTRs) and other genetic
      elements, the rise of lentiviral technology and the emergence of regulated vector
      systems providing tissue-restricted transgene expression and RNA interference,
      are profoundly changing the landscape of stem cell-based therapies. New
      developments in vector design and an increasing understanding of the mechanisms
      underlying insertional oncogenesis are ushering in a new phase in hematopoietic
      stem cell (HSC) engineering, thus bringing the hitherto exclusive reliance on LTR
      driven, gamma-retroviral vectors to an end. Based on their ability to transduce
      non-dividing cells and their genomic stability, lentiviral vectors offer new
      prospects for the manipulation of HSCs. Tissue-specific vectors, as exemplified
      by globin vectors, not only provide therapeutic efficacy, but may also enhance
      safety, insofar that they restrict transgene expression in stem cells, progenitor
      cells and blood cells in all but the transcriptionally targeted lineage. This
      review provides a survey of these advances as well as several remaining
      challenges, focusing in particular on the importance of achieving adequate levels
      of protein expression from a limited number of vector copies per cell-ideally one
      to two.

PMID- 17228319
TI  - Th17 cells: An orphan with influence.

PMID- 17228318
TI  - Cytokine regulation of immunopathology in toxoplasmosis.
AB  - Toxoplasma gondii infection is an important cause of central nervous system and
      ocular disease, both in immunocompromised and in certain immunocompetent
      populations. Although parasite-mediated host cell lysis is probably the principal
      cause of tissue destruction in immunodeficiency states, hypersensitivity and
      inflammatory responses may underlie severe disease in otherwise immuno-sufficient
      individuals. In this review, we have critically evaluated the body of
      experimental evidence indicating a role of CD4 T cells in systemic and local
      immunopathology associated with T. gondii infection. We also discuss the
      pathogenic roles of cytokines produced by T helper (Th) 1 and Th17 cells and the
      protective and homeostatic roles of interleukin (IL)-10, transforming growth
      factor-beta and IL-27 in modulating hypersensitivity responses induced by T.
      gondii.

PMID- 17228320
TI  - Immunopathogenesis of poxvirus infections: forecasting the impending storm.
AB  - Variola virus, the causative agent of smallpox, is a member of the poxvirus
      family and one of the most virulent human pathogens known. Although smallpox was
      eradicated almost 30 years ago, it is not understood why the mortality rates
      associated with the disease were high, why some patients recovered, and what
      constitutes an effective host response against infection. As variola virus
      infects only humans, our current understanding of poxvirus infections comes
      largely from historical clinical data from smallpox patients and from animal
      studies using closely related viruses such as ectromelia, myxoma and monkeypox.
      The outcome of an infection is determined by a complex interaction between the
      type of immune response mounted by the host and by evasion mechanisms that the
      virus has evolved to subvert it. Disease pathogenesis is also a function of both
      host and viral factors. Poxviruses are not only cytopathic, causing host tissue
      damage, but also encode an array of immunomodulatory molecules that affect the
      severity of disease. The ability of the host to control virus replication is
      therefore critical in limiting tissue damage. However, in addition to targeting
      virus, the immune response can inadvertently damage the host to such a degree
      that it causes illness and even death. There is growing evidence that many of the
      symptoms associated with serious poxvirus infections are a result of a 'cytokine
      storm' or sepsis and that this may be the underlying cause of pathology.

PMID- 17228321
TI  - Lymphoid organogenesis: Educating stroma.

PMID- 17228322
TI  - Activation-induced upregulation of inhibitory killer Ig-like receptors is
      regulated by protein kinase C.
AB  - Inhibitory killer Ig-like receptor (KIR) expression was upregulated by protein
      kinase C (PKC) activation in stable Jurkat clones that express KIR or CD8KIR
      fusion proteins. PKC-induced KIR upregulation was mediated by the cytoplasmic
      tail of KIR and regulated at the post-transcriptional level. PKC inhibition,
      metabolic labeling and colocalization studies demonstrated that the activation of
      the conventional PKCs upregulated surface and cellular KIR levels by stimulating
      the maturation processes in endoplasmic reticulum-Golgi and by promoting the
      recycling of surface KIR through sorting endosomes. Similar studies also revealed
      that KIR was secreted to plasma membrane through lytic granules in a PKCdelta
      dependent manner. Consequently, PKCdelta inhibition caused the formation of giant
      perinuclear granules, which trapped KIR and FasL as well as CPE and Lamp1.

PMID- 17228323
TI  - Tyrosine kinase Syk associates with toll-like receptor 4 and regulates signaling
      in human monocytic cells.
AB  - Toll-like receptor 4 (TLR4) induces an innate immune response in mammals by
      recognizing lipopolysaccharide (LPS), a component of the cell wall of Gram
      negative bacteria. In this study, we show that tyrosine kinase Syk constitutively
      associates with TLR4 in THP-1 cells. As previously reported in peripheral blood
      mononuclear cells, TLR4 gets inducibly tyrosine phosphorylated upon LPS
      engagement in THP-1 cells. Piceatannol, a pharmacological inhibitor of the
      tyrosine kinase Syk, abrogates TLR4 tyrosine phosphorylation at low doses. The
      kinetics of TLR4 tyrosine phosphorylation in THP-1 cells coincides with an early
      wave of Syk tyrosine phosphorylation. Additionally, serine threonine kinase
      interleukin-1 (IL1) receptor-associated kinase 1 (IRAK-1) is transiently
      recruited to the complex containing adaptor molecule MyD88, TLR4 and Syk within 1
      min of LPS engagement and dissociates by 30 min. Finally, the inhibition of Syk
      with piceatannol has no effect on LPS-mediated release of cytokines IL6, IL1beta,
      tumor necrosis factor-alpha, neither on chemokines macrophage inhibitory protein
      (MIP)1alpha, MIP1beta, monocyte chemoattractant protein -1, IL8, Groalpha and
      RANTES. However, IL10 and IL12p40 releases are significantly inhibited. Our
      findings implicate Syk as a novel modulator of LPS-mediated TLR4 responses in
      human monocytic cells and shed insight into the kinetics of early complex
      formation upon LPS engagement.

PMID- 17228324
TI  - Inhibition of apoptosis induced by heat shock preconditioning is associated with
      decreased phagocytosis in human polymorphonuclear leukocytes through inhibition
      of Rac and Cdc42.
AB  - The functionality of polymorphonuclear leukocytes (PMNL) and the exact process of
      the protective program employed by these cells in response to the heat shock (HS)
      remain ill-defined and debated. Particularly, the mechanism of phagocytic
      impairment induced by the HS and the molecular events associated with the delay
      of apoptosis used by these cells in such condition have given conflictual data.
      The aim of the present work is to study the consequences of the HS in different
      pathways involved in human PMNL apoptosis and subsequently in human PMNL
      phagocytic function. We demonstrated that HS (41 degrees C, 1 h) preconditioning
      induced inhibition of spontaneous PMNL apoptosis observed at 18 h in control
      cells incubated at 37 degrees C. This inhibition was characterized by absence of
      morphological nuclear changes, decrease of DNA fragmentation, low level of
      annexin V expression and decrease of caspase-3 activity. In parallel, HS
      increased both Hsp70 and Mcl-1 protein levels in PMNL. Phagocytosis of latex
      beads by PMNL was inhibited by HS (41 degrees C, 1 h) preconditioning despite an
      upregulation of CD11b, CD16 and CD47. Moreover, HS induced prolonged F actin
      depolymerization and inhibited both Rac and Cdc42 activation in PMNL. Finally,
      our results identify a new function of Mcl-1 in HS protection against apoptosis.

PMID- 17228325
TI  - Transient transmission of porcine endogenous retrovirus to fetal lambs after pig
      islet tissue xenotransplantation.
AB  - Evidence for the in vivo transmission of porcine endogenous retrovirus (PERV)
      from porcine xenografts to various recipient animals has been inconsistent. To
      characterize the contribution of the host immune system to the potential for PERV
      transmission from pig islet tissue xenografts to host tissues, we examined two
      immunoincompetent animal models, thymectomizsed fetal lambs and NODscid mice. Pig
      proislets were grafted into fetal lambs or adult NODscid mice. Conventional,
      nested and real-time PCR/RT-PCR tests were used to search for PERV and pig cell
      specific sequences (porcine mitochondrial cytochrome oxidase II (COII) or
      mitochondrial ribosomal 12S) in pig proislets, host liver and spleen at 5-84 days
      (lambs) or 96 days (mice) after transplantation. Xenografts were harvested at the
      same time points. The copy number of PERV sequences and host cell-specific
      nuclear (palmitoylcarnitine transferase) sequences was assessed by real-time PCR
      to estimate the proportion of PERV-infected host cells. Pig proislets were shown
      to be PERV+ve by PCR and immunohistochemistry (PERV B env protein p15E). PERV
      transmission (PERV A, B or C DNA in the absence of porcine COII or 12S sequences)
      was detected by nested PCR and real-time PCR in 4/12 fetal lamb liver samples 5
      23 days after transplantation; the maximum copy number of PERV B env sequences
      was found at day 5 (700 copies/1 x 10(6) lamb cells). A total of 4/12 fetal lambs
      demonstrated both PERV and 12S porcine sequences in liver samples (days 5-84) by
      real-time PCR, suggesting that pig cells had migrated to those tissues and
      established microchimerism; nested PCR showed evidence for microchimerism
      (porcine COII sequences alone) in 2/12 lambs (day 5). The incidence of PERV
      transmission and frequency of microchimerism was similar in host spleen analysed
      by real-time PCR. Histological examination showed complete xenograft rejection by
      23 days after transplantation to fetal lambs. In contrast, pig proislet
      xenografts survived long term (> or =day 96) in NODscid mice but no PERV
      transmission was found. Both nested and real-time PCR assays revealed that 2/3
      mice had become microchimeric. Long-term expression of PERV A, B and C as well as
      porcine 12S or COII RNAs was found at the graft site (day 96) only, indicating
      that PERV transcription and possibly replication, continued in the donor pig
      islet tissue after transplantation. Overall, detection of PERV transmission and
      microchimerism was limited by the sensitivity of the PCR assay and the primers
      chosen. The absence of stable PERV transmission and microchimerism in fetal lambs
      and the rejection of pig proislet xenografts correlated in time with the
      establishment of host immunocompetence. We therefore suggest that the frequent
      failure to identify PERV transmission late after transplantation could be due to
      the immunological destruction of PERV-infected host cells. Recipient NODscid mice
      demonstrated long-term microchimerism and intragraft PERV expression, which was
      consistent with their stable immunoincompetence.

PMID- 17228326
TI  - Progranulin mutations in Dutch familial frontotemporal lobar degeneration.
AB  - Mutations in the progranulin (PGRN) gene have recently been identified in
      frontotemporal lobar degeneration with ubiquitin inclusions linked to chromosome
      17q21. We report here the finding of two novel frameshift mutations and three
      possible pathogenic missense mutations in the PGRN gene. Furthermore, we
      determined the frequency of PGRN mutations in familial cases recruited from a
      large population-based study of frontotemporal lobar degeneration carried out in
      The Netherlands.

PMID- 17228327
TI  - Association of PDCD1 polymorphisms with childhood-onset systemic lupus
      erythematosus.
AB  - A regulatory single nucleotide polymorphism (SNP) PD1.3G/A located on programmed
      cell death 1 (PDCD1) gene, was shown to be involved in susceptibility to systemic
      lupus erythematosus (SLE) in Swedish, European American, and Mexican cases.
      However, association to childhood-onset SLE has not been analyzed. The aim of
      this study was to investigate the association of PDCD1 polymorphisms and
      haplotypes with susceptibility to childhood-onset SLE in Mexican population.
      Three PDCD1 SNPs, PD1.3G/A, PD1.5C/T, PD1.6G/A, were analyzed in 250 childhood
      onset SLE Mexican patients and 355 healthy controls in a case-control association
      study. Polymorphisms were genotyped by TaqMan technology. Stratification analysis
      was performed on the SLE cohort to investigate the SNP association with renal
      disorder. In addition, haplotypes were constructed with these three SNPs. The
      PD1.3A allele was significantly associated to childhood-onset SLE (P=0.0019, odds
      ratio (OR) 2.73, 95% confidence interval (95% CI) 1.35-5.56). The other PDCD1
      SNPs did not show association. A total of 155 patients (62%) had nephritis, and
      no association was observed with PDCD1 SNPs. The ACG haplotype (PD1.3A, PD1.5C,
      PD1.6G) included almost all PD1.3A alleles, and it was more frequent in SLE
      patients (5.5%) than in controls (2.1%) (P=0.003; OR 2.73, 95% CI 1.37-5.46). The
      haplotype structure in Mexican controls was significantly different from those
      reported in Spanish and Swedish. Our results support association of the PD1.3A
      SNP to susceptibility of childhood-onset SLE in Mexican population and does not
      show association to lupus nephritis in this age group.

PMID- 17228328
TI  - Partial duplications of the MSH2 and MLH1 genes in hereditary nonpolyposis
      colorectal cancer.
AB  - Numerous reports have highlighted the contribution of MSH2 and MLH1 genomic
      deletions to hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch's
      syndrome, but genomic duplications of these genes have been rarely reported.
      Using quantitative multiplex PCR of short fluorescent fragments (QMPSF), 962 and
      611 index cases were, respectively, screened for MSH2 and MLH1 genomic
      rearrangements. This allowed us to detect, in 11 families, seven MSH2
      duplications affecting exons 1-2-3, exons 4-5-6, exon 7, exons 7-8, exons 9-10,
      exon 11, and exon 15, and three MLH1 duplications affecting exons 2-3, exon 4 and
      exons 6-7-8. All duplications were confirmed by an independent method. The
      contribution of genomic duplications of MSH2 and MLH1 to HNPCC can therefore be
      estimated approximately to 1% of the HNPCC cases. Although this frequency is much
      lower than that of genomic deletions, the presence of MSH2 or MLH1 genomic
      duplications should be considered in HNPCC families without detectable point
      mutations.

PMID- 17228329
TI  - Spindle regulation in neural precursors of flies and mammals.
AB  - The mitotic spindle is the cellular scaffold that facilitates proper segregation
      of genetic material during cell division. Far from being static, the spindle is a
      dynamically regulated tool that can alter its size, shape and position during
      mitosis. Work in both insect and vertebrate systems has shown that regulation of
      this structure involves an array of highly conserved proteins. Moreover, it is
      now clear that tight regulation of the spindle during the process of neurogenesis
      is paramount to proper cell division and generation of the nervous system as a
      whole.

PMID- 17228330
TI  - Motoring along with the bacterial RecA protein.
AB  - The recombinases of the RecA family are often viewed only as DNA-pairing proteins
      - they bind to one DNA segment, align it with homologous sequences in another DNA
      segment, promote an exchange of DNA strands and then dissociate. To a first
      approximation, this description seems to fit the eukaryotic (Rad51 and Dmc1) and
      archaeal (RadA) RecA homologues. However, the bacterial RecA protein does much
      more, coupling ATP hydrolysis with DNA-strand exchange in a manner that greatly
      expands its repertoire of activities. This article explores the protein
      activities and experimental results that have identified RecA as a motor protein.

PMID- 17228331
TI  - Impaired firing and sodium channel function in CA1 hippocampal interneurons after
      transient cerebral ischemia.
AB  - Although interneurons in area CA1 of the hippocampus are less vulnerable to
      cerebral ischemia than CA1 pyramidal cells, it is not clear whether their
      relatively intact cellular morphology implies preservation of normal function. As
      maintenance of cellular excitability and firing properties is essential for
      interneurons to regulate neural networks, we investigated these aspects of
      interneuronal function after transient cerebral ischemia in rats. Cerebral
      ischemia in rats was induced for 8 mins by a combination of bilateral common
      carotid artery occlusion and hypovolemic hypotension, and whole cell patch clamp
      recordings were made in hippocampal slices prepared 24 h after reperfusion.
      Interneurons located within stratum pyramidale of area CA1 exhibited normal
      membrane properties and action potentials under these conditions. However, their
      excitability had declined, as evidenced by an increased action potential
      threshold and a rightward shift in the relationship between injected depolarizing
      current and firing rate. Voltage-clamp experiments revealed that transient
      cerebral ischemia reduced the peak Na(+) current and shifted Na(+) channel
      activation to more depolarized values, but did not alter steady-state
      inactivation of the channel. Double immunofluorescence cytochemistry showed that
      transient cerebral ischemia also reduced Na(v)1.1 subunit immunoreactivity in
      interneurons that coexpressed parvalbumin. We conclude that transient cerebral
      ischemia renders CA1 interneurons less excitable, that depressed excitability
      involves impaired Na(+) channel activation and that Na(+) channel dysfunction is
      explained, at least in part, by reduced expression of the Na(v)1.1 subunit. These
      changes may promote interneuron survival, but might also contribute to pyramidal
      cell death.

PMID- 17228332
TI  - The upregulation of glial glutamate transporter-1 participates in the induction
      of brain ischemic tolerance in rats.
AB  - Glial glutamate transporter-1 (GLT-1) plays an essential role in removing
      glutamate from the extracellular space and maintaining the glutamate below
      neurotoxic level in the brain. To explore whether GLT-1 plays a role in the
      acquisition of brain ischemic tolerance (BIT) induced by cerebral ischemic
      preconditioning (CIP), the present study was undertaken to observe in vivo
      changes in the expression of GLT-1 and glial fibrillary acidic protein (GFAP) in
      the CA1 hippocampus during the induction of BIT, and the effect of dihydrokainate
      (DHK), an inhibitor of GLT-1, on the acquisition of BIT in rats.
      Immunohistochemistry for GFAP showed that the processes of astrocytes were
      prolonged after a CIP 2 days before the lethal ischemic insult, which could
      protect pyramidal neurons in the CA1 hippocampus against delayed neuronal death
      induced normally by lethal ischemic insult. The prolonged processes extended into
      the area between the pyramidal neurons and tightly surrounded them. These changes
      made the pyramidal layer look like a 'shape grid'. Simultaneously, the prolonged
      and extended processes showed a great deal of GLT-1. Western blotting analysis
      showed significant upregulation of GLT-1 expression after the CIP, especially
      when it was administered 2 days before the subsequent lethal ischemic insult.
      Neuropathological evaluation by thionin staining showed that DHK dose-dependently
      blocked the protective role of CIP against delayed neuronal death induced
      normally by lethal brain ischemia. It might be concluded that the surrounding of
      pyramidal neurons by astrocytes and upregulation of GLT-1 induced by CIP played
      an important role in the acquisition of the BIT induced by CIP.

PMID- 17228333
TI  - Cerebral glutamine and glutamate levels in relation to compromised energy
      metabolism: a microdialysis study in subarachnoid hemorrhage patients.
AB  - Astrocytic glutamate (Glt) uptake keeps brain interstitial Glt levels low. Within
      the astrocytes Glt is converted to glutamine (Gln), which is released and
      reconverted to Glt in neurons. The Glt-Gln cycle is energy demanding and impaired
      energy metabolism has been suggested to cause low interstitial Gln/Glt ratios.
      Using microdialysis (MD) measurements from visually noninjured cortex in 33
      neurointensive care patients with subarachnoid hemorrhage, we have determined how
      interstitial Glt and Gln, as a reflection of the Glt-Gln cycle turnover, relate
      to perturbed energy metabolism. A total of 3703 hourly samples were analyzed. The
      lactate/pyruvate (L/P) ratios correlated to the Gln/Glt ratios (r=-0.66), but
      this correlation was not stronger than the correlation between L/P and Glt
      (r=0.68) or the correlation between lactate and Glt (r=0.65). A novel observation
      was a linear relationship between interstitial pyruvate and Gln (r=0.52). There
      were 13 periods (404 h) of 'energy crisis', defined by L/P ratios above 40. All
      were associated with high interstitial Glt levels. Periods with L/P ratios above
      40 and low pyruvate levels were associated with decreased interstitial Gln
      levels, suggesting ischemia and failing astrocytic Gln synthesis. Periods with
      L/P ratios above 40 and normal or high pyruvate levels were associated with
      increased interstitial Gln levels, which may represent an astrocytic
      hyperglycolytic response to high interstitial Glt levels. The results imply that
      moderately elevated L/P ratios cannot always be interpreted as failing energy
      metabolism and that interstitial pyruvate levels may discriminate whether or not
      there is sufficient astrocytic capacity for Glt-Gln cycling in the brain.

PMID- 17228334
TI  - The relationship between the pleiotropic phenotypic effects of a mutation fixed
      by selection.
AB  - A pleiotropic model of mutation is presented that allows for correlations between
      the effects of a new mutation and for the distribution of mutational effects to
      vary from being leptokurtic to normally distributed. Using this model I quantify
      how selection transforms the correlation between the effects of a new (random)
      mutation into the correlation between the effects of a mutation that is fixed by
      selection and contributes to an adaptation. Results suggest that under most
      conditions the correlation between the effects of a fixed mutation is less than
      the correlation between the effects of a new mutation. I also generalize previous
      results that quantified the expected size of a fixed mutation's effect on a
      character given an observed effect of that mutation on another character. In
      agreement with previous results, work here suggests that as the observed effect
      becomes large and beneficial the expected effect on another character approaches
      the expected effect of a new (random) mutation given the observed effect. Lastly,
      these theoretical results are related to recent empirical work that found
      beneficial mutations had a positive correlation in their pleiotropic effects.

PMID- 17228335
TI  - Effects of d-amphetamine and buprenorphine combinations on speedball
      (cocaine+heroin) self-administration by rhesus monkeys.
AB  - The simultaneous i.v. administration of heroin and cocaine, called a 'speedball,'
      is often reported clinically, and identification of effective pharmacotherapies
      is a continuing challenge. We hypothesized that treatment with combinations of a
      monoamine releaser d-amphetamine, and a mu partial agonist, buprenorphine, might
      reduce speedball self-administration by rhesus monkeys. Speedballs (0.01
      mg/kg/inj cocaine+0.0032 mg/kg/inj heroin) and food (1 g banana-flavored pellets)
      were available during four daily sessions on a second-order schedule of
      reinforcement (fixed ratio (FR)2 (variable ratio (VR)16:S)). Monkeys were treated
      for 10 days with saline or ascending doses of d-amphetamine (0.0032-0.032
      mg/kg/h)+buprenorphine (0.075 or 0.237 mg/kg/day) in combination. d
      Amphetamine+both doses of buprenorphine produced an amphetamine dose-dependent
      decrease in speedball self-administration in comparison to the saline treatment
      baseline (P<0.01-0.001), but food-maintained responding did not change
      significantly. d-Amphetamine alone (0.032 mg/kg/h) significantly decreased both
      food (P<0.01) and speedball-maintained responding (P<0.05). During saline control
      treatment, speedball unit doses of 0.0032 mg/kg/inj cocaine+0.001 mg/kg/inj
      heroin were at the peak of the speedball dose-effect curve. Daily treatment with
      0.01 mg/kg/h d-amphetamine+0.237 mg/kg/day buprenorphine produced a significant
      downward and rightward shift in the speedball dose-effect curve (P<0.01) and no
      significant effect on food-maintained responding. A significant decrease in
      speedball self-administration was sustained over 10 days of treatment. These
      findings are consistent with our previous reports and suggest that medication
      mixtures designed to target both the stimulant and the opioid component of the
      speedball may be an effective approach to polydrug abuse treatment.

PMID- 17228336
TI  - Nicotine dependence, symptoms and oxidative stress in male patients with
      schizophrenia.
AB  - The high rate of smoking in schizophrenia may reflect patients' attempts to
      reduce the side effects of antipsychotic medications, and one mechanism for this
      reduction may be a reduction in oxidative stress and free radical-mediated brain
      damage that may contribute to schizophrenic symptoms and to complications of its
      treatment. Symptoms were assessed with the Positive and Negative Syndrome Scale
      (PANSS), side effects were assessed with the Simpson and Angus Rating Scale
      (SAS), and malondialdehyde (MDA), superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px) and catalase (CAT) activities were measured in plasma. All of
      these measures were compared in 130 male inpatients with DSM-IV schizophrenia:
      104 smokers and 26 non-smokers. The results showed that the positive PANSS
      symptoms were lower in smokers than non-smokers (14.5 vs 17.5), while the
      negative symptoms were lower in those who smoked more cigarettes (r=-0.23). The
      SAS showed no differences. The CAT activity was correlated with both GSH-Px and
      SOD activities. Of the three enzymes only the CAT activity was significantly
      higher in smokers than non-smokers (2.9 vs 1.6 U/ml), but greater SOD activity
      correlated more cigarettes smoked (r=0.24). Consistent with some protection
      against oxidative stress, MDA also was significantly lower in smokers than non
      smokers (9.2 vs 14.4 nmol/ml). The fewer positive symptoms in smokers and fewer
      negative symptoms in those who smoked more cigarettes may be a selection bias,
      but appears to be associated with decreased oxidative stress and lipid
      peroxidation in schizophrenics who smoke tobacco.

PMID- 17228338
TI  - Minocycline attenuates hyperlocomotion and prepulse inhibition deficits in mice
      after administration of the NMDA receptor antagonist dizocilpine.
AB  - The present study was undertaken to examine whether the second generation
      antibiotic drug minocycline attenuates behavioral changes (eg, acute
      hyperlocomotion and prepulse inhibition (PPI) deficits) in mice after the
      administration of the N-methyl-D-aspartate (NMDA) receptor antagonist (+)-MK-801
      (dizocilpine). Dizocilpine (0.1 mg/kg)-induced hyperlocomotion was significantly
      attenuated by pretreatment with minocycline (40 mg/kg). Furthermore, the PPI
      deficits after a single administration of dizocilpine (0.1 mg/kg) were attenuated
      by pretreatment with minocycline (10, 20, or 40 mg/kg), in a dose-dependent
      manner. Moreover, in vivo microdialysis study in the free-moving mice revealed
      that pretreatment with minocycline (40 mg/kg, i.p.) significantly attenuated the
      increase of extracellular dopamine (DA) levels in the frontal cortex and striatum
      after administration of dizocilpine (0.1 mg/kg), suggesting that the inhibition
      of dizocilpine-induced DA release by minocycline may, at least in part, be
      implicated in the mechanism of action of minocycline with respect to dizocilpine
      induced behavioral changes in mice. These findings suggest that minocycline could
      attenuate behavioral changes in mice after the administration of the NMDA
      receptor antagonist dizocilpine. Therefore, it is possible that minocycline would
      be a potential therapeutic drug for schizophrenia.

PMID- 17228339
TI  - Significant increase in the aggressive behavior of transgenic mice overexpressing
      peripheral progastrin peptides: associated changes in CCK2 and serotonin
      receptors in the CNS.
AB  - The gastrin precursor peptide, progastrin (PG), is secreted from enteroendocrine
      cells in the intestine and increased in patients with hypergastrinemia and
      colorectal cancers. In recent years, we and others have demonstrated an important
      role of PG peptides in colorectal carcinogenesis, and were surprised to note
      significant changes in the behaviors of transgenic mice overexpressing PGs. In
      the present studies, we examined emotional behaviors of transgenic mice
      overexpressing PG in the intestinal and peripheral circulation. Aggression,
      locomotor activity and anxiety-like behaviors of the homozygous transgenic
      (Tg/Tg) mice and the wild-type (WT) littermates were examined by
      intruder/resident test, open field and elevated plus maze, respectively. A
      significant increase in the aggression, locomotor activity, and anxiety-like
      behaviors was detected in the Tg/Tg vs WT mice. As CCK, CCK(2) receptors
      (CCK(2)R), and 5-HT(1A) receptors (5-HT(1A)R) in the CNS play an important role
      in these behaviors, possible changes in the expression of CCK and CCK(2)R and the
      density of CCK(2)R and 5-HT(1A)R were determined by either real-time RT-PCR or
      autoradiography of ligand binding assays. The results suggest that the
      expressions of CCK and CCK(2)R were increased in the hypothalamus, and the
      density of CCK(2)R were increased in the hypothalamus and amygdala of Tg/Tg vs WT
      mice. Similarly, the density of 5-HT(1A)R was increased in the hypothalamus. Our
      results suggest that an upregulation of the CCK response system and 5-HT(1A)R in
      the hypothalamus of Tg/Tg mice may mediate the alterations in the observed
      behaviors of these mice.

PMID- 17228337
TI  - Atomoxetine reverses nicotine withdrawal-associated deficits in contextual fear
      conditioning.
AB  - Recent evidence suggests that the cognitive symptoms of nicotine withdrawal and
      the cognitive symptoms of attention deficit hyperactivity disorder (ADHD) may
      share neural correlates. Thus, therapeutics that ameliorate ADHD symptoms may
      also ameliorate nicotine-withdrawal symptoms. The present research tested this
      hypothesis in an animal model of nicotine withdrawal-associated cognitive
      deficits using atomoxetine, a norepinephrine reuptake inhibitor that is approved
      by the FDA to treat the symptoms of ADHD. C57BL/6 mice were prepared with osmotic
      minipumps that administered 6.3 mg/kg/day of nicotine or saline, and the
      minipumps were removed after 12 days of continuous treatment. Twenty-four hours
      later, mice were trained in delay fear conditioning using two paired
      presentations of an auditory conditioned stimulus (CS) with a footshock
      unconditioned stimulus. Testing for freezing in response to the training context
      and for freezing in response to the CS occurred the next day. Nicotine-withdrawn
      mice and their saline-treated counterparts received either saline or atomoxetine
      before training and the context test. Consistent with previous research, the
      results indicate that mice withdrawn from chronic nicotine demonstrated lower
      levels of contextual fear conditioning than mice that were not withdrawn from
      chronic nicotine. Atomoxetine dose-dependently reversed the deficit, suggesting
      that nicotine withdrawal may be associated with changes in noradrenergic
      function, acetylcholinergic function, and/or with changes in cell signaling
      cascades that are activated by both nicotine and norepinephrine. These data
      suggest that atomoxetine may be efficacious for treating nicotine withdrawal
      associated cognitive deficits that promote relapse in abstinent smokers.

PMID- 17228340
TI  - Brief RU 38486 treatment normalizes the effects of chronic stress on calcium
      currents in rat hippocampal CA1 neurons.
AB  - Chronic stress alters many properties in rat brain, like serotonin responsiveness
      and dendritic morphology. In the present study, we examined (i) whether
      unpredictable stress during 21 days affects calcium (Ca) currents of CA1
      pyramidal neurons recorded on day 22; and (ii) if so, whether this change is
      normalized by treatment with the glucocorticoid receptor-antagonist RU 38486
      during days 18-21. At 3 weeks of unpredictable stress increased the amplitude of
      the peak and sustained calcium current components, determined in hippocampal
      slices prepared from animals under rest (ie, with low corticosterone levels). The
      increased Ca-current amplitude was associated with an enhanced cell capacitance;
      current density was not significantly affected by chronic stress. In slices from
      stressed rats that received RU 38486, no stress-induced enhancement of calcium
      current amplitude was seen, while RU 38486 by itself did not alter calcium
      currents in handled controls. We confirmed earlier observations that brief in
      vitro treatment with 100 nM corticosterone, thus substantially activating the low
      affinity glucocorticoid receptors, increases Ca-current amplitude recorded 1-4 h
      later in slices from naive rats. However, Ca-current amplitude was not affected
      by corticosterone applied to slices from handled controls and currents were even
      decreased by corticosterone given to slices from chronically stressed rats,
      suggesting that corticosterone effects depend on the history of the animal. In
      conclusion, the data indicate that chronic stress, RU 38486 treatment as well as
      acute rises in corticosterone level strongly modulate calcium influx into CA1
      neurons. This could have consequences for the viability of these neurons.

PMID- 17228341
TI  - The diurnal cortisol cycle in delinquent male adolescents and normal controls.
AB  - Patterns of low hypothalamus-pituitary-adrenal (HPA) activity have been observed
      in antisocial groups. As conflicting results have been reported in children and
      adolescents, the aim of this study was to further investigate HPA activity in
      antisocial behavior by studying the relationship between the diurnal cortisol
      cycle, as well as the cortisol awakening response (CAR), and antisocial behavior
      in male adolescents. The diurnal cortisol cycle and the CAR during the first hour
      after awakening were compared between 12- to 14-year-old boys who attended a
      delinquency diversion program (DP), with and without a disruptive behavior
      disorder (DBD) (respectively DP+; n=24 and DP-; n=65), and matched normal
      controls (NC; n=32). The DP+ group, but not the DP- group, showed a significantly
      slower decrease of cortisol during the diurnal cycle than the NC group.
      Furthermore, the DP+ group had significantly lower cortisol levels in the first
      hour after awakening as compared with the NC group. The results indicate altered
      HPA activity in delinquent boys with a DBD. Etiological mechanisms, directions
      for future research, and clinical implications are discussed.

PMID- 17228342
TI  - Moderate increase in dietary sucrose does not influence fasting or postprandial
      serum lipids regardless of the presence of apolipoprotein E2 allele in healthy
      subjects.
AB  - OBJECTIVE: To investigate whether a moderate increase in dietary sucrose intake
      induces different serum lipid responses in normolipidemic subjects with the
      epsilon 2 allele compared with subjects without the epsilon 2 allele. DESIGN:
      Controlled, parallel study. SUBJECTS: There were 15 subjects with the
      apolipoprotein E (APOE)3/2 genotype and 19 subjects with the APOE 3/3 or 3/4
      genotype, whose mean+/-s.d. age was 48+/-14 and 35+/-10 years, respectively. All
      subjects had normal glucose metabolism. INTERVENTIONS: The subjects were
      instructed to increase their sucrose intake by 40 g/day for 8 weeks and to
      decrease the intake of saturated and unsaturated fat to maintain energy balance.
      Dietary adherence was monitored using food records and the actual increase in
      sucrose intake was 39.8+/-18.4 g/day. Sixteen subjects (nine with APOE 3/2
      genotype, seven with APOE 3/3 or 3/4 genotypes) participated also in an 8 h oral
      fat tolerance test at the beginning and at the end of the intervention. RESULTS:
      Body weight remained stable during the intervention. Sucrose intake did not have
      a significant effect on fasting concentrations of serum total and lipoprotein
      lipids, plasma glucose, serum insulin, squalene and non-cholesterol sterols in
      either genotype group. Neither were there any changes in postprandial lipid or
      insulin responses. CONCLUSIONS: Moderate increase in sucrose intake does not
      affect fasting or postprandial serum lipid responses in healthy subjects with or
      without the epsilon 2 allele.

PMID- 17228343
TI  - Mexican anthropometric percentiles for ages 10-18.
AB  - OBJECTIVE: To elaborate Mexican growth charts based on international methodology.
      DESIGN: Data were obtained from the Mexican National Health Survey. The survey
      was stratified and probabilistic representative of all the country. SETTING:
      Nationwide open population living in urban and rural areas. SUBJECTS: Boys (8545)
      and girls (9983) from 10 to 18 years participating in the survey. METHODS: Age,
      weight and height were recorded. Empirical percentiles were calculated and
      smoothed. Smoothed curves were approximated using least-mean square estimation.
      RESULTS: Tables and figures for percentile values of weight, height and body mass
      index (BMI) for age, as well as percentile values of weight and BMI for height
      for both genders are presented. Regarding 50th BMI for age percentiles, Mexicans
      had higher levels than the Americans in the Centers for Disease Control and
      Prevention growth charts; Mexicans were lower but had similar weights than the
      Americans. Owing to the high BMI, the percentile corresponding to an overweight
      level (25 kg/m(2)) at 18 years was 74.5 in boys and 72.5 in girls, whereas
      obesity level (30 kg/m(2)) at 18 years was 97.3 and 97.4 in boys and girls,
      respectively. CONCLUSIONS: The present growth charts are snapshots of a Mexican
      population. Because of the high median BMI compared to US and World Health
      Organization standards, we must be cautious in establishing an upper normal
      cutoff for clinical normality, not merely selecting the 85th and 95th percentiles
      as equivalents of overweight and obesity, respectively. Therefore, we proposed
      percentiles 74.5 in boys and 72.5 in girls as the action points of overweight as
      they are the percentiles corresponding to BMI 25 kg/m(2) at 18 years.
      SPONSORSHIP: The survey was supported by the Mexican Minister of Health.
      Statistical analyses were sponsored by Dr Del-Rio-Navarro.

PMID- 17228345
TI  - High intake of milk, but not meat, decreases bone turnover in prepubertal boys
      after 7 days.
AB  - OBJECTIVE: To compare the short-term effect of a high milk and a high meat
      intake, identical in protein amount, on bone turnover during prepuberty. SETTING:
      A University department. DESIGN AND SUBJECTS: From 28, randomly recruited, 8-year
      old boys, first 14 were assigned to the milk group and next 14 to the meat group.
      In each group, 12 boys finished the dietary intervention. INTERVENTION: Milk (1.5
      l/day) and meat (250 g/d), both containing approximately 53 g of protein, were
      given together with the habitual diet for 7 days. At baseline and day-7, serum
      osteocalcin (s-OC), bone-specific alkaline phosphatase (s-BAP) and C-terminal
      telopeptides of type I collagen (s-CTX) were measured (immunoassay) and dietary
      intake was estimated (a 3-day weighted food record). RESULTS: Baseline s-OC, s
      BAP and s-CTX were not significantly different between the groups. After 7 days,
      the average protein intake increased in both groups by 47.5 g; the milk group had
      higher (P<0.0001) calcium intake; s-OC and s-CTX decreased (P< or =0.04) in the
      milk group (-30.9%; -18.7%, respectively) compared with the meat group (+6.4%; 
      1.0%, respectively) and s-BAP decreased (P=0.06) both in the milk (-3.9%) and the
      meat group (-7.5%). CONCLUSIONS: At the equal protein intake, milk, but not meat,
      decreased bone turnover in prepubertal boys after 7 days. This effect was
      probably due to some milk-derived compounds, rather than to the total protein
      intake. Future studies should elucidate the mechanism(s) of milk-related decline
      of bone turnover and its relevance for peak bone mass during growth. SPONSORSHIP:
      University PhD scholarships.

PMID- 17228344
TI  - B-group vitamins, MTHFR C677T polymorphism and carotid intima-media thickness in
      clinically healthy subjects.
AB  - OBJECTIVE: Plasma B-group vitamins and age may affect the carotid intima-media
      thickness (IMT) in subjects with different 677TT genotype of the
      methylenetetrahydrofolate reductase (MTHFR) gene. DESIGN: A hospital-based cross
      study. SETTING: Genomic and Vascular Center, Changhua Christian Hospital,
      Changhua, Taiwan. SUBJECTS: Five hundred and forty-one clinically healthy
      subjects. INTERVENTION: Fasting plasma, homocysteine (Hcy), vitamin B(6), vitamin
      B(12), folate and B-mode carotid ultrasound. RESULTS: MTHFR genotype, plasma
      concentrations of folate, vitamin B(6) and vitamin B(12) and age were
      significantly correlated to the plasma Hcy concentration. MTHFR 677TT carriers
      had higher concentrations of Hcy than did subjects with the CC and CT genotypes.
      Age, sex, body mass index and plasma Hcy were independent contributors to
      increase carotid IMT. However, with stratification by mean value of age and B
      group vitamins concentrations, we found that at advanced age, lower plasma folate
      and vitamin B(12) were three risk factors involved in the enhancing effect of the
      MTHFR 677TT genotype on the increase of plasma Hcy and carotid IMT. CONCLUSION:
      MTHFR 677TT-related carotid atherosclerosis was only identified in healthy
      elderly subjects with lower level of plasma folate and vitamin B(12).
      SPONSORSHIP: Changhua Christian Hospital.

PMID- 17228346
TI  - Parental perceptions of feeding practices in five European countries: an
      exploratory study.
AB  - OBJECTIVE: To gain an insight into parental perceptions of infant feeding
      practices in five European countries. DESIGN: An exploratory investigation using
      focus group discussions. Various aspects addressed included social and cultural
      setting for the consumption of food, infant feeding practice and behaviour,
      consumer health awareness and sources of information, and attitudes towards a
      healthy infant diet. SETTING: Focus group participants were recruited from
      centres in five countries, Germany, Italy, Scotland, Spain and Sweden, with three
      focus groups being conducted in each centre. SUBJECTS: A total of 108 parents
      with infants up to the age of 12 months participated in focus group discussions
      across these centres. METHODS: Focus groups were conducted with participants from
      centres in five countries. RESULTS: The majority of parents in this study chose
      to initiate breastfeeding and prepare infant food at home. Parents did not
      strictly adhere to infant feeding guidelines when introducing complementary foods
      into their infant's diets. There were cross-cultural differences in sources of
      information on infant feeding practice with the paediatrician in Germany, Italy
      and Spain. The health visitor in Scotland and the child welfare clinics in Sweden
      were the most popular sources. CONCLUSIONS: A number of cultural differences and
      similarities in attitudes towards infant feeding practice were revealed. This
      makes European wide approaches to promoting healthy infant feeding difficult as
      different infant feeding practices are influenced not only by parental
      perceptions but also by advice from health professionals and feeding guidelines.
      Further data need to be available on parents' attitudes and beliefs towards
      infant feeding practice to investigate further the rationale for differing
      beliefs and attitudes towards infant feeding practice. SPONSORSHIP: EU Fifth
      Framework QLRT 2002 02606.

PMID- 17228347
TI  - Effect of weight loss on the postprandial response to high-fat and high
      carbohydrate meals in obese women.
AB  - OBJECTIVE: To assess the effect of weight loss on the plasma lipid and remnant
      like lipoprotein cholesterol (RLPc) response to a high-fat or a high-carbohydrate
      meal in a population of obese women. DESIGN: Nutritional intervention study.
      SUBJECTS: Sixteen obese women (mean body mass index (BMI): 37.6+/-5 kg/m(2)).
      METHODS: Subjects were asked to follow an energy-restricted diet (800 kcal/day)
      for 7 weeks, followed by a 1-week maintenance diet. Before and after weight loss,
      each participant was given (in random order) two iso-energetic meals containing
      either 80% fat and 20% protein (the high-fat meal) or 80% carbohydrate and 20%
      protein (the high-carbohydrate meal). Blood samples were collected over the
      following 10-h period. A two-way analysis of variance with repeated measures was
      used to assess the effect of the meal and postprandial time on biological
      variables and postprandial responses (notably RLPc levels). RESULTS: Weight loss
      was associated with a significant decrease in fasting triglyceride (P=0.0102),
      cholesterol (P<0.0001), low-density lipoprotein cholesterol (P=0.0003), high
      density lipoprotein-cholesterol (P=0.0009) and RLPc (P=0.0015) levels. The
      triglyceride response to the high-fat meal was less intense after weight
      reduction than before (interaction P<0.002). This effect persisted after
      adjustment on baseline triglyceride levels. The triglyceride response to the high
      carbohydrate meal was biphasic (i.e. with two peaks, 1 and 6 h after carbohydrate
      intake). After adjustment on baseline values, weight reduction was associated
      with a trend towards a reduction in the magnitude of the second triglyceride peak
      (interaction P<0.054). In contrast, there was no difference in postprandial RLPc
      responses before and after weight loss, again after adjustment on baseline
      levels. CONCLUSION: Our data suggest that weight loss preferentially affects
      postprandial triglyceride metabolism.

PMID- 17228348
TI  - Preventing excessive weight gain during pregnancy - a controlled trial in primary
      health care.
AB  - OBJECTIVE: To investigate whether individual counselling on diet and physical
      activity during pregnancy can have positive effects on diet and leisure time
      physical activity (LTPA) and prevent excessive gestational weight gain. DESIGN: A
      controlled trial. SETTING: Six maternity clinics in primary health care in
      Finland. The clinics were selected into three intervention and three control
      clinics. SUBJECTS: Of the 132 pregnant primiparas, recruited by 15 public health
      nurses (PHN), 105 completed the study. INTERVENTIONS: The intervention included
      individual counselling on diet and LTPA during five routine visits to a PHN until
      37 weeks' gestation; the controls received the standard maternity care. RESULTS:
      The counselling did not affect the proportion of primiparas exceeding the weight
      gain recommendations or total LTPA when adjusted for confounders. The adjusted
      proportion of high-fibre bread of the total weekly amount of bread decreased more
      in the control group than in the intervention group (difference 11.8%-units, 95%
      confidence interval (CI) 0.6-23.1, P=0.04). The adjusted intake of vegetables,
      fruit and berries increased by 0.8 portions/day (95% CI 0.3-1.4, P=0.004) and
      dietary fibre by 3.6 g/day (95% CI 1.0-6.1, P=0.007) more in the intervention
      group than in the control group. There were no high birth weight babies (>or=4000
      g) in the intervention group, but eight (15%) of them in the control group
      (P=0.006). CONCLUSIONS: The counselling helped pregnant women to maintain the
      proportion of high-fibre bread and to increase vegetable, fruit and fibre
      intakes, but was unable to prevent excessive gestational weight gain.

PMID- 17228349
TI  - Similar serum plant sterol responses of human subjects heterozygous for a
      mutation causing sitosterolemia and controls to diets enriched in plant sterols
      or stanols.
AB  - OBJECTIVE: We investigated the serum phytosterol responses of heterozygous
      relatives of sitosterolemia patients to diets enriched in phytosterols or
      stanols. DESIGN: Randomized double-blind crossover design. SETTING: Muenster,
      Germany. SUBJECTS: Eight heterozygous and 13 control subjects were recruited. One
      heterozygote and three controls dropped out. INTERVENTIONS: Seven heterozygotes
      and 10 controls received daily portions of margarine containing 2 g of plant
      sterols, 2 g of stanols or a control margarine for 6 weeks each in a randomized
      order. These phases were intercepted by wash-out periods of 6 weeks each.
      RESULTS: Compared to the control period, serum phytosterol concentrations
      increased overall by more than 20% when subjects consumed the plant sterol
      margarine (F((1,15))=8.719, P=0.01), with no significant difference between
      heterozygotes (mean +14.5 (s.d. 17.2) micromol/l, +23.0%) and controls (+4.9
      (9.9) micromol/l, +20.5%; F((1,15))=2.168, P=0.162), but decreased when subjects
      consumed the stanol-enriched margarine (F((1,15))=12.124, P=0.003), again to a
      similar extent in heterozygotes (-34.2 (41.2) micromol/l, -54.2%) and controls (
      12.2 (9.2) micromol/l, -50.6%; F((1,15))=2.729, P=0.119). The lowest total serum
      concentrations of cholesterol and phytosterols were seen after the diet enriched
      in stanols. Serum stanol concentrations increased on this diet, but on a very low
      level and never exceeded 0.05% of serum cholesterol levels in any subject.
      CONCLUSIONS: Serum phytosterol concentrations increased only moderately in
      heterozygotes consuming a diet enriched in phytosterols, indicating that they
      retained considerable capacity to excrete phytosterols even at higher intakes.

PMID- 17228350
TI  - Body composition by the four-compartment model: validity of the BOD POD for
      assessing body fat in Mexican elderly.
AB  - OBJECTIVE: The aims of this study were to validate BOD POD in a wide sample of
      healthy and independent Mexican elderly men and women subjects using the 4
      compartment (4C) model as the reference method, and to evaluate the assumptions
      of the densitometric two-compartment (2C) model. DESIGN: Cross-sectional study
      designed to assess body composition and validation of a method based on 2C model
      (BOD POD). SETTING: Urban and rural regions of Sonora, Mexico. SUBJECTS: Two
      hundred and two free-living subjects >or=60 years old were completed in this
      study. METHODS: Body density and body fat were measured by the BOD POD, total
      body water by deuterium dilution and total body bone ash by dual energy X-ray
      absorptiometry. Body composition was determined using Baumgartner's equation.
      RESULTS: Percent body fat by the 4C model was 31.2 and 42.5% in men and women,
      respectively (P<0.001). Group mean accuracy of body fat by BOD POD against that
      of the 4C model showed an effect of sex (P<0.001), but not the method (P=0.27).
      Results of individual accuracy showed no significant difference with the identity
      line and the slope was significantly different from zero or a slope similar to
      one. Precision assessed by model R (2) was high for all subjects and for men and
      women by separate. The standard error of the estimate was low for all and for men
      and women by separate. Bland and Altman analysis showed no significant bias.
      CONCLUSION: The BOD POD technique is a valid and reliable method compared to the
      4C model and it could be applied in subjects with similar physical and
      anthropometric characteristics to subjects of this study.

PMID- 17228351
TI  - Different antioxidant profiles in Italian centenarians: the Sardinian
      peculiarity.
AB  - In this study, 153 Italian centenarians from four different geographical areas,
      including Modena (northern Italy), Ancona (central Italy), Perugia (central
      Italy) and Sardinia island (AKEA Project) were enrolled. Plasma levels of vitamin
      C, uric acid, vitamin A and vitamin E as well as the activities of superoxide
      dismutase and glutathione peroxidase were measured. Subjects were compared to a
      younger control population of the same areas, divided into three age groups:
      <or=60; 61-80 and 81-99 years. The main result of this study is that, whereas in
      Italian population elevated levels of plasma vitamins A and E seem to be
      important for longevity, this do not apply to centenarians from Sardinia, in
      which probably other factors play a more important role.

PMID- 17228352
TI  - Bias in height and weight reported by Swedish adolescents and relations to body
      dissatisfaction: the COMPASS study.
AB  - OBJECTIVE: To assess the size of biases in self-reported height, weight in a
      large sample of adolescents with special attention to possible effects of body
      dissatisfaction and to assess how such biases may influence estimates of
      overweight and obesity. DESIGN: Cross-sectional study. SETTING: Unselected
      population from Southwestern parts of Stockholm County, Sweden. SUBJECTS: Two
      thousand seven hundred and twenty-six boys and girls, 15 years of age. METHODS:
      Data were collected by a questionnaire answered by adolescents and a physical
      examination made by trained study nurses. A validated physical appearance scale
      and body silhouettes were embedded into the questionnaire. RESULTS: Obese boys
      under-reported their weight (5.2 kg) (95% confidence intervals (CI) 3.7; 6.6)
      more than obese girls (3.8 kg) (95% CI 1.8; 5.8). Agreement between self-reported
      and measured body mass index (BMI)-categories (obese, overweight and non
      overweight/obese) as estimated by weighted kappa was 0.77 (95% CI 0.72; 0.82) for
      girls and 0.74 (95% CI 0.70; 0.79) for boys. For obese girls and boys sensitivity
      of self-reports were 0.65 (95% CI 0.47; 0.79) and 0.52 (95% CI 0.38; 0.66). Boys
      with low scores on the physical appearance scale under-reported their weight and
      BMI more than those with high scores. Boys and girls who wished to be leaner
      under-reported their weight and BMI more than subjects who were satisfied with
      their body size (P<0.05). CONCLUSION: Thirty-five percent of obese girls and 48%
      of obese boys would remain undetected from self-reported data. Boys and girls who
      were dissatisfied with their physical appearance or size under-reported their
      weight more than satisfied subjects.

PMID- 17228353
TI  - Prognostic indicators in metastatic spinal cord compression: using functional
      independence measure and Tokuhashi scale to optimize rehabilitation planning.
AB  - STUDY DESIGN: Retrospective, descriptive study. OBJECTIVE: To determine if
      patients with metastatic spinal cord compression (MSCC) make significant
      functional gains through rehabilitation. To study survival and predictors of
      survival in MSCC. To explore predictive factors for high or low functional gains
      in MSCC. SETTING: Inpatient neuro-oncology rehabilitation ward, Henderson General
      Hospital, Hamilton, Canada. METHODS: Clinical records were examined for 63
      inpatients with MSCC. Demographics, treatment of MSCC, length of rehabilitation,
      admission, and discharge Functional Independence Measure (FIM) scores, Tokuhashi
      score and survival data were collected. Statistical analyses included
      nonparametric comparisons, Kaplan-Meier analyses, Cox regression, and exploratory
      logistic regression. RESULTS: FIM score improved from 83 to 102 (P<0.0001).
      Estimated median survival from time of rehabilitation was 10.0 months. Kaplan
      Meier analysis showed longer survival in patients with high Tokuhashi scores (9
      15) compared to low scores (0-8) (P<0.005); and high FIM change (>13) compared to
      low FIM change (< or =13) (P<0.02). Cox regression revealed that high FIM gain
      and high Tokuhashi score were prognostic factors. Logistic regression showed
      Tokuhashi score (odds ratio (OR)=1.30, 95% confidence interval (CI)=1.04-1.62)
      and length of rehabilitation (OR=1.04, 95% confidence interval (CI)=1.01-1.07)
      were associated with high FIM gain. CONCLUSIONS: Rehabilitation improves
      functional outcomes in MSCC. Patients who had a high Tokuhashi score and achieved
      high functional gains after rehabilitation had longer survival. Tokuhashi score
      and length of rehabilitation were associated with high FIM gain. The Tokuhashi
      score can help identify patients with good prognosis and potential for
      improvement during rehabilitation.

PMID- 17228354
TI  - Epidemiology of spinal cord injuries in the 2005 Pakistan earthquake.
AB  - STUDY DESIGN: Prospective observational study. OBJECTIVES: To identify the
      epidemiological features specific to spinal injuries as a result of an
      earthquake. SETTINGS: Rawalpindi, Pakistan in the months after the 8 October 2005
      earthquake. METHODS: In the month after the earthquake, the one established
      rehabilitation center was augmented with two makeshift spinal cord centers.
      Information on mechanism of injury, mode of evacuation, associated injuries was
      gathered, and a detailed clinical and radiological assessment was performed.
      Neurological status and functional outcome was determined after 10 weeks.
      RESULTS: Of an estimated 650-750 spinal cord injuries, 187 were admitted to these
      centers, including 80 men and 107 women with a mean age of 28.3+/-12.4 years.
      Injuries occurred while standing in 57.8% of patients. Most (83.4%) who reached
      the spinal cord center were airlifted. A urinary catheter had been placed before
      admission in 91.5%. Most of the patients were paraplegic 89.3, with 50.8%
      incomplete injuries. Fracture or fracture dislocation was present in 70, and 75%
      underwent spinal fixation. Although pressure ulcers (28.9%) and urinary tract
      infections (39%) were common, deep venous thromboses (4.8%) and depression (5.8%)
      were seldom detected. At 10 weeks, 75% were continent or performing intermittent
      catheterization. There were no deaths and two births. CONCLUSION: After a
      disaster, evacuation of persons with a spinal cord injury to a specialized center
      results in low mortality. Response planning for disasters should include early
      aggressive medical rehabilitation.

PMID- 17228356
TI  - Endogenous risk factors for deep-vein thrombosis in patients with acute spinal
      cord injuries.
AB  - STUDY DESIGN: Case-control study. AIM OF THE STUDY: Investigate the presence of
      additional endogenous risk factors of deep-vein thrombosis (DVT). SETTING:
      Regional Spinal Unit of Florence, Italy. METHODS: A total of 43 patients with
      spinal lesion and a history of DVT during the acute stage of their neurological
      impairment (Group A) were comprehensively evaluated and the blood concentrations
      of the following risk factors, that are presumably associated with DVT, were
      determined: antithrombin III (ATIII), protein C (PC), protein S (PS), factor V
      Leiden, gene 200210A polymorphism, homocysteine (Hcy), inhibitor of plasminogen
      activator-1 (PAI-1) and lipoprotein A (LpA). The control group (Group B)
      consisted of 46 patients matched to Group A for sex, age, neurological status and
      prophylactic treatment during the acute stage, with no history of DVT.
      Statistical analysis was performed using the Mann-Whitney and Fisher's exact
      tests. RESULTS: Of the individuals in Group A, 14% had no risk factor and 86% had
      at least one; however, in Group B 54% had no endogenous risk factors and 46% had
      at least one. None of the individuals in either group had a deficit in their
      coagulation inhibitors (ATIII, PC and PS), and the LpA level was equivalent in
      the two groups. The levels of Hcy and PAI-1 were significantly higher in Group A.
      CONCLUSIONS: Increases in the levels of plasma Hcy and PAI-1 are demonstrated to
      be independent risk factors for developing a DVT.

PMID- 17228357
TI  - Spinal epidural Rosai-Dorfman disease preceding by relapsing uveitis: a case
      report with literature review.
AB  - STUDY DESIGN: Case report. SETTING: Tertiary referral center hospital in Taiwan.
      OBJECTIVES: To report a case of spinal Rosai-Dorfman disease (RDD) presenting
      with paraparesis and also preceding by relapsing uveitis for 6 months. A thoracic
      laminectomy was performed to remove the solid mass. The pathological diagnosis
      reveals infiltrating histiocytes, emperipolesis and positivity for S-100. There
      is no recurrence 1 year later with MR imaging. CONCLUSIONS: The relapsing
      idiopathic uveitis may be a prodrome for this unusual disease, because RDD is
      associated closely to defective immunogical response. Early and accurate
      diagnosis of CNS RDD may reverse the neurologic deficits by early decompression.

PMID- 17228355
TI  - Impact of spinal cord injury on self-perceived pre- and postmorbid cognitive,
      emotional and physical functioning.
AB  - STUDY DESIGN: Cross-sectional study with repeated measurements. OBJECTIVES: To
      examine the patient's perspective of the impact of spinal cord injury (SCI) on
      physical, cognitive, emotional function, and quality of life (QOL). SETTING:
      Australia. METHODS: A sample of 63 patients with SCI, 32 of whom had recent
      injuries, and 31 with established injuries were administered the Ruff
      Neurobehavioral Inventory to examine patients' subjective evaluation of pre- and
      post-injury functioning. Current happiness levels were also evaluated using the
      Subjective Happiness Scale. A follow up assessment was performed 6 months later
      to examine changes over time. RESULTS: A significant difference was found between
      perception of pre- and postmorbid function on composite Cognitive (t=5.99, df=62,
      P<0.001), Physical (t=11.56, df=62, P<0.001), and QOL (t=7.16, df=62, P<0.001)
      scales and on several of the Emotional subscales including anxiety, paranoia and
      suspicion, and substance abuse (P<0.001). A series of hierarchical regression
      analyses indicate that post-SCI pain was a significant predictor of: cognitive
      (R(2)=0.20, P<0.001); emotional (R(2)=0.13, P<0.004); and of QOL (R(2)=0.22,
      P<0.001) functioning. With the exception of a decrease in happiness (P<0.01),
      there were no significant changes in any measures over the 6 month time period.
      CONCLUSIONS: There are significant changes in patients' perceptions of physical
      and cognitive functioning, and of QOL before and after SCI and some aspects of
      emotional functioning. Pain has a significant adverse effect on functioning.
      Happiness decreased slightly in the 6 months between surveys.

PMID- 17228358
TI  - Resistance training and locomotor recovery after incomplete spinal cord injury: a
      case series.
AB  - STUDY DESIGN: Longitudinal intervention case series. OBJECTIVE: To determine if a
      12-week resistance and plyometric training program results in improved muscle
      function and locomotor speed after incomplete spinal cord injury (SCI). SETTING:
      University research setting. METHODS: Three ambulatory individuals with chronic
      (18.7+/-2.2 months post injury) motor incomplete SCI completed 12 weeks of lower
      extremity resistance training combined with plyometric training (RPT). Muscle
      maximum cross-sectional area (max-CSA) of the knee extensor (KE) and plantar
      flexor (PF) muscle groups was determined using magnetic resonance imaging (MRI).
      In addition, peak isometric torque, time to peak torque (T (20-80)), torque
      developed within the initial 220 ms of contraction (torque(220)) and average rate
      of torque development (ARTD) were calculated as indices of muscle function.
      Maximal as well as self-selected gait speeds were determined pre- and post-RPT
      during which the spatio-temporal characteristics, kinematics and kinetics of gait
      were measured. RESULTS: RPT resulted in improved peak torque production in the KE
      (28.9+/-4.4%) and PF (35.0+/-9.1%) muscle groups, as well as a decrease in T(20
      80), an increased torque(220) and an increase ARTD in both muscle groups. In
      addition, an increase in self-selected (pre-RPT=0.77 m/s; post-RPT=1.03 m/s) and
      maximum (pre-RPT=1.08 m/s; post-RPT=1.47 m/s) gait speed was realized. Increased
      gait speeds were accompanied by bilateral increases in propulsion and hip
      excursion as well as increased lower extremity joint powers. CONCLUSIONS: The
      combination of lower extremity RPT can attenuate existing neuromuscular
      impairments and improve gait speed in persons after incomplete SCI.

PMID- 17228359
TI  - 'Endotoxin tolerance': TNF-alpha hyper-reactivity and tubular cytoresistance in a
      renal cholesterol loading state.
AB  - The term 'endotoxin tolerance' defines a state in which prior endotoxin
      (lipopolysaccharide (LPS)) exposure induces resistance to subsequent LPS attack.
      However, its characteristics within kidney have not been well defined. Hence,
      this study tested the impact of LPS 'preconditioning' (LPS-PC; 18 or 72 h
      earlier) on: (i) selected renal inflammatory mediators (tumor necrosis factor
      (TNF)-alpha, interleukin-10 (IL-10), monocyte chemotactic protein-1 (MCP-1),
      inducible nitric oxide synthase (iNOS), Toll-like receptor 4 (TLR4); protein or
      mRNA); (ii) cholesterol homeostasis (a stress reactant); and (iii) isolated
      proximal tubule (PT) vulnerability to hypoxia or membrane cholesterol
      (cholesterol oxidase/esterase) attack. Two hours post LPS injection, LPS-PC mice
      manifested reduced plasma TNF-alpha levels, consistent with systemic LPS
      tolerance. However, in kidney, paradoxical TNF-alpha hyper-reactivity
      (protein/mRNA) to LPS existed, despite normal TLR4 protein levels. PT TNF-alpha
      levels paralleled renal cortical results, implying that PTs were involved. LPS-PC
      also induced: (i) renal cortical iNOS, IL-10 (but not MCP-1) mRNA hyper
      reactivity; (ii), PT cholesterol loading, and (iii) cytoresistance to hypoxia and
      plasma membrane cholesterol attack. A link between cholesterol homeostasis and
      cell LPS responsiveness was suggested by observations that cholesterol reductions
      in HK-2 cells (methylcyclodextrin), or reductions in HK-2 membrane fluidity
      (A2C), blunted LPS-mediated TNF-alpha/MCP-1 mRNA increases. In sum: (i) systemic
      LPS tolerance can be associated with renal hyper-responsiveness of selected
      components within the LPS signaling cascade (e.g., TNF-alpha, iNOS, IL-10); (ii)
      PT cytoresistance against hypoxic/membrane injury coexists; and (iii) LPS-induced
      renal/PT cholesterol accumulation may mechanistically contribute to each of these
      results.

PMID- 17228360
TI  - Preserved leukocyte CD11b expression at the site of interstitial inflammation in
      patients with high-flux hemodiafiltration.
AB  - The impact of high-flux hemodialysis on clinical outcomes remains controversial.
      We have previously shown that in vivo transmigrated leukocytes from patients with
      low-flux bioincompatible hemodialysis have an impaired capacity to upregulate
      CD11b at the site of interstitial inflammation. In the present study, we
      investigated the in vivo capacity of transmigrated monocytes and granulocytes to
      express CD11b at the site of interstitial inflammation in 10 patients on
      biocompatible high-flux hemodiafiltration or high-flux hemodialysis and 12
      healthy subjects, and the in vitro response to a bacteria-related peptide (N
      formyl-methionyl-leucyl-phenylalanine (fMLP)). Leukocyte formation of hydrogen
      peroxide (H(2)O(2)) and leukocyte apoptosis were also studied. In patients, both
      monocytes and granulocytes had a preserved capacity to express CD11b following in
      vivo transmigration to sites of interstitial inflammation, compared with cells
      from healthy subjects. Furthermore, monocytes and granulocytes from patients
      showed a preserved ability to respond to challenge with fMLP in the extravascular
      milieu. The intracellular killing capacity of leukocytes (H(2)O(2) production) in
      the interstitium was similar as of cells from healthy subjects both before and
      after stimulation with fMLP. Following maximal receptor independent stimulation
      (phorbol 12-myristate 13-acetate), leukocytes from patients showed lower H(2)O(2)
      production at the site of intense inflammation, compared with cells from healthy
      subjects. Finally, leukocyte apoptosis in interstitial inflammation was similar
      in patients and healthy subjects. We conclude that in vivo transmigrated
      leukocytes from patients on biocompatible high-flux hemodiafiltration or high
      flux hemodialysis have a preserved capacity to express CD11b at the site of
      interstitial inflammation. This may have important biological implications.

PMID- 17228361
TI  - Variants of C1GALT1 gene are associated with the genetic susceptibility to IgA
      nephropathy.
AB  - IgA nephropathy (IgAN) is a polygenic disorder and the precise role of genetic
      factors remains elusive. Increasing evidences have implicated the aberrant
      galactosylation of IgA1 molecules in the pathogenesis of IgAN. The
      galactosyltransferase, core 1 beta3-Gal-T, and its chaperone, Cosmc, play
      important roles in beta1,3 glycosylation of IgA1 molecule. A case-control
      association study was performed to investigate the association between single
      nucleotide polymorphisms (SNPs) of C1GALT1 and C1GALT1C1 genes and the
      susceptibility to IgAN. A total of 1164 subjects were enrolled, including 670
      IgAN patients and 494 geographically matched healthy controls. Five SNPs, 
      734C/T, -465A/G, -330G/T, -292C/-, and 1365G/A in C1GALT1 were selected as
      tagging SNPs. The D allele and DD genotype of -292C/- in IgAN patients were
      significantly lower than in the controls (P<0.01). The frequency of haplotype
      YATIG (Y=C or T) was significantly lower in patients than in controls (0.0719 vs
      0.1168, P=2.775 x 10(-4), odds ratio (OR)=0.70). The haplotype YAGDA (0.1236 vs
      0.0791, P=3.815 x 10(-3), OR=1.77) and YATDG (0.0840 vs 0.0298, P=1.258 x 10(-5),
      OR=3.03) were significantly higher in patients than in controls. The present
      study suggested that the polymorphisms of C1GALT1 gene were associated with the
      genetic susceptibility to IgAN in Chinese population.

PMID- 17228362
TI  - Eosinophilic glomerulonephritis in children in Southwestern Uganda.
AB  - Acute renal disease is common in sub-Saharan Africa, with high mortality. Its
      etiology is poorly understood; quartan malaria owing to Plasmodium malariae was
      implicated in previous series. Few previous studies have included histological
      data; furthermore, much of the literature pre-dates the human immunodeficiency
      virus (HIV) epidemic. We report prospective analysis of acute proteinuric renal
      disease in children in rural Uganda. Clinical and laboratory data are presented
      on 65 patients (aged 2-14 years, mean 8.4; 35 male, 30 female) in 41 of whom
      histological diagnosis was obtained by renal biopsy. The most frequent
      histological finding was endocapillary proliferative glomerulonephritis (GN) in
      27/41 cases, in 20 of which eosinophils were very prominent. No cases showed
      features of HIV nephropathy. Malarial films were positive in 11 cases: all owing
      to Plasmodium falciparum. Patients were treated with diuretics,
      antihypertensives, and supportive measures. Corticosteroids were rarely used,
      being reserved for patients with minimal changes on renal biopsy. Clinical
      outcomes were fair: 91% of patients survived to discharge. We conclude that acute
      GN is common in children in Uganda, that an unusual eosinophilic proliferative GN
      is the most frequent histological finding, that HIV is not implicated as an
      important factor in this age group, and that good outcomes can be achieved using
      simple clinical and laboratory diagnostic methods. Renal biopsy in selected cases
      is feasible and helpful, especially in allowing rational use of corticosteroids
      and other potentially toxic treatments. Symptomatic treatments and careful
      supportive care will allow the majority of children to recover.

PMID- 17228363
TI  - Decreased in vitro osteoblast proliferation and low turnover bone disease in
      nonuremic proteinuric patients.
AB  - Patients with proteinuria, even those with normal glomerular filtration rate,
      often present abnormal bone histology. We evaluated bone histology and the in
      vitro proliferation of osteoblasts in samples obtained from 17 proteinuric
      patients with primary glomerulopathies. Histomorphometric analysis of bone
      biopsies was performed, and bone fragments were obtained for osteoblast culture,
      in which we evaluated cell proliferation. In comparison to controls, patients
      presented lower trabecular bone volume (20.9+/-14.5% vs 26.8+/-5.9%; P=0.0008);
      lower trabecular number (1.7+/-0.2/mm vs 2.0+/-0.3/mm; P=0.004); and greater
      trabecular separation (475.5+/-96.4 microm vs 368.3+/-86.2 microm, P=0.0002). We
      also found alterations in bone formation and resorption: lower osteoid volume
      (0.9+/-0.7% vs 2.0+/-1.4%; P=0.0022); lower osteoid thickness (6.4+/-2.8 microm
      vs 11.5+/-3.2 microm; P<0.0001); less mineralizing surface (4.6+/-3.1% vs 13.5+/
      6.0%; P<0.0001); lower bone formation rate (0.03+/-0.04 microm(3)/microm(2)/day
      vs 0.09+/-0.05 microm(3)/microm(2)/day; P<0.0001); and greater osteoclast surface
      (0.35+/-0.6 vs 0.05+/-0.1%, P=0.0016). Mean in vitro osteoblast proliferation was
      lower in patients than in controls (910.2+/-437.1 vs 2261.0+/-1121.0 d.p.m./well,
      P=0.0016). Serum concentrations of 25-hydroxyvitamin-D(3) correlated negatively
      with proteinuria and positively with in vitro osteoblast proliferation. Our
      results demonstrate that nonuremic proteinuric glomerulonephritic patients
      present bone structure disorder, low bone formation and high bone resorption, as
      well as low osteoblast proliferation.

PMID- 17228365
TI  - Fimbrial lectins influence the chemokine repertoire in the urinary tract mucosa.
AB  - The defense against mucosal infections relies on chemokines that recruit
      inflammatory cells to the mucosa. This study examined if the chemokine response
      to uro-pathogenic Escherichia coli is influenced by fimbrial expression. The CXC
      (CXCL1, CXCL5, CXCL8, CXCL9, CXCL10) and CC chemokines (CCL2, CCL3, CCL5) were
      quantified after in vitro infection of uro-epithelial cells with a fimbriated E.
      coli pyelonephritis isolate, or with P or type 1 fimbriated transformants of an
      avirulent E. coli K-12 strain. The response profile was shown to vary with the
      fimbrial type. Type 1 fimbriated E. coli elicited mainly CXCL1 and CXCL8, whereas
      P fimbriated E. coli stimulated CCL2 and CCL5 and class II were more potent
      chemokine inducers than class III P fimbriae. Chemokines were also quantified in
      urine samples from 73 patients with febrile urinary tract infection, and analyzed
      as a function of disease severity and fimbrial expression by the strain infecting
      each patient. A complex CXC and CC chemokine response was detected in patient
      urine, with a significant influence of the fimbrial type. The results show that
      virulence factors like fimbriae may modify the mucosal chemokine response. This
      mechanism may allow the host to adjust the inflammatory cell infiltrate to fit
      the infecting strain.

PMID- 17228364
TI  - Role of mesothelial cell-derived granulocyte colony-stimulating factor in
      interleukin-17-induced neutrophil accumulation in the peritoneum.
AB  - Recent studies suggest that peritoneal CD4(+) T lymphocytes may control
      recruitment of polymorphonuclear leukocytes (PMN) during peritonitis by an
      interleukin-17 (IL-17)-dependent mechanism. IL-17 and granulocyte colony
      stimulating factor (G-CSF) have been proposed to form an axis that regulates PMN
      transmigration. Here we report on the role of G-CSF released by human peritoneal
      mesothelial cells (HPMCs) in IL-17A-mediated peritoneal PMN accumulation. In
      vitro exposure of HPMCs to IL-17A resulted in a time- and dose-dependent release
      of G-CSF. This effect was related to the induction of G-CSF mRNA and mediated
      through the nuclear factor-kappaB (NF-kappaB) pathway. The novel observation was
      that IL-17A-stimulated NF-kappaB activation in HPMCs followed a biphasic profile,
      with an early induction (45 min), followed by the return to basal levels (90
      min), and a delayed induction (3 h). Tumor necrosis factor alpha synergistically
      amplified IL-17A-induced G-CSF production by enhanced NF-kappaB activation and
      through stabilization of G-CSF mRNA. Intraperitoneal (i.p.) administration of IL
      17A in Balb/c mice resulted in increased local levels of G-CSF and selective PMN
      accumulation. Administration of anti-G-CSF blocking antibody before IL-17A
      injection significantly reduced the IL-17A-triggered PMN infiltration. This
      effect occurred despite increased i.p. levels of PMN-specific chemokines KC and
      macrophage inflammatory protein-2 seen in animals treated with anti-G-CSF
      antibody. These data demonstrate that the mesothelium-derived G-CSF plays an
      important role in IL-17A-induced PMN recruitment into the peritoneum.

PMID- 17228366
TI  - The importance of transitions between dialysis and transplantation in the care of
      end-stage renal disease patients.
AB  - Analyses describing outcomes of kidney transplantation usually exclude the
      survival of wait-listed patients and dialysis patients with failed kidney
      transplants, and thus reflect only a portion of the typical transplant process.
      We determined death rates during the continuum of wait-listing, transplantation,
      and after allograft failure among adult end-stage renal disease patients in the
      United States between 1995 and 2003. Before transplantation, death rates
      increased with longer waiting times. Death rates were lowest during the period of
      allograft function and highest after allograft failure. Patients were at
      particularly high risk during periods of transition between dialysis and
      transplantation (death rates during the peri-transplant period and during the re
      initiation of dialysis after transplant failure were 8.2/100 patient-years (95%
      confidence interval (CI) 7.7, 8.8) and 17.9/100 patient-years (95% CI 15.7,
      20.3), respectively compared to 6.4/100 patient-years (95% CI 6.25, 6.51) during
      the period of wait-listing. Diabetic patients and older patients were at
      increased risk at all time points. The most common known cause of death in all
      age subgroups was cardiovascular disease. The proportion of death owing to sepsis
      was greatest after allograft failure (16.8% of all deaths were due to sepsis
      compared to 14.0% during wait-listing, and 12.7% during the period of allograft
      function). Consideration of the entire transplant experience as a whole should
      help to focus patient care on periods of particularly high risk, and emphasizes
      opportunities to improve outcomes by strategies aimed at preventing death owing
      to cardiovascular and infectious causes.

PMID- 17228367
TI  - Basolateral carbonic anhydrase IV in the proximal tubule is a
      glycosylphosphatidylinositol-anchored protein.
AB  - Carbonic anhydrase (CA) IV facilitates HCO(3) reabsorption in the renal proximal
      tubule by catalyzing the reversible hydration of CO(2). CAIV is tethered to cell
      membranes via a glycosylphosphatidylinositol (GPI) lipid anchor. As there is
      basolateral as well as apical CAIV staining in proximal tubule, the molecular
      identity of basolateral CAIV was examined. Biotinylation of confluent monolayers
      of rat inner medullary collecting duct cells stably transfected with rabbit CAIV
      showed apical and basolateral CAIV, and in the cell transfectants expressing high
      levels of CAIV, a transmembrane form was targeted to the basolateral membrane.
      Basolateral expression of CAIV ( approximately 46 kDa) was confirmed in normal
      kidney tissue by Western blotting of vesicle fractions enriched for basolateral
      membranes by Percoll density fractionation. We examined the mode of membrane
      linkage of basolaterally expressed CAIV in the kidney cortex. CAIV detected in
      basolateral or apical membrane vesicles exhibited similar molecular size by
      sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis following
      deglycosylation, and was equally sensitive to phosphatidylinositol-specific
      phospholipase C digestion, indicating that CAIV is expressed on the basolateral
      membrane as a GPI-anchored protein. Half of the hydratase activity of basolateral
      vesicles was resistant to SDS denaturation, compatible with being CAIV. Thus, GPI
      anchored CAIV resides in the basolateral membrane of proximal tubule epithelia
      where it may facilitate HCO(3) reabsorption via association with kNBC1.

PMID- 17228370
TI  - Dichromated pullulan diffraction gratings: influence of environmental conditions
      and storage time on their properties.
AB  - Investigations of the environmental stability of diffraction gratings, recorded
      in dichromated pullulan (DCP), are reported. Profile changes of DCP surface
      relief gratings, under high humidity conditions, were analyzed using an atomic
      force microscope. It was found that the profile was not altered, while the
      diffraction efficiency was preserved. The influence of storage life on the
      diffraction efficiency and surface profile of DCP gratings were also
      investigated. It was concluded that DCP gratings offer much better stability
      compared with the dichromated gelatin.

PMID- 17228369
TI  - Fiber grating sensing interrogation based on an InGaAs photodiode linear array.
AB  - We present a new method of the fiber grating sensing interrogation technique by
      utilizing an indium gallium arsenide photodiode linear array and blazed fiber
      Bragg gratings. An interrogation system based on an InGaAs photodiode linear
      array is designed, and the system performance is analyzed. The interrogation
      system shows a good prospect for smart sensing.

PMID- 17228371
TI  - Parallel-slab polarizing beam splitter and photopolarimeter.
AB  - A dielectric-slab polarizing beam splitter (PBS) is described that generates two
      parallel beams of orthogonal p and s linear polarizations in reflection and
      functions as a diattenuator in transmission. The plane-parallel slab, which is
      set at Brewster's angle, is uncoated on one side and has an s-polarization
      antireflection coating (s-ARC) on the other side. Analytical results are
      presented for a PBS that uses a high-index slab coated with a low-index single
      layer s-ARC, which is particularly suited for the IR. A novel multistage
      photopolarimeter that uses two such PBSs in series is described as being capable
      of sequential and simultaneous measurement of all four Stokes parameters of
      light.

PMID- 17228368
TI  - The normal kidney filters nephrotic levels of albumin retrieved by proximal
      tubule cells: retrieval is disrupted in nephrotic states.
AB  - The origin of albuminuria remains controversial owing to difficulties in
      quantifying the actual amount of albumin filtered by the kidney. Here we use
      fluorescently labeled albumin, together with the powerful technique of intravital
      2-photon microscopy to show that renal albumin filtration in non-proteinuric rats
      is approximately 50 times greater than previously measured and is followed by
      rapid endocytosis into proximal tubule cells (PTCs). The endocytosed albumin
      appears to undergo transcytosis in large vesicles (500 nm in diameter),
      identified by immunogold staining of endogenous albumin by electron microscopy,
      to the basolateral membrane where the albumin is disgorged back to the
      peritubular blood supply. In nephrotic rats, the rate of uptake of albumin by the
      proximal tubule (PT) is decreased. This is consistent with reduced expression of
      clathrin, megalin, and vacuolar H(+)-ATPase A subunit, proteins that are critical
      components of the PT endocytotic machinery. These findings strongly support the
      paradigm-shifting concept that the glomerular filter normally leaks albumin at
      nephrotic levels. Albuminuria does not occur as this filtered albumin load is
      avidly bound and retrieved by PTCs. Dysfunction of this retrieval pathway leads
      to albuminuria. Thus, restoration of the defective endocytotic and processing
      function of PT epithelial cells might represent an effective strategy to limit
      urinary albumin loss, at least in some types of nephrotic syndrome.

PMID- 17228372
TI  - Three-dimensional direct-write lithography into photopolymer.
AB  - We demonstrate a three-dimensional direct-write lithography system capable of
      writing deeply buried, localized index structures into diffusion-mediated
      photopolymer. The system is similar to that used for femtosecond writing in
      glass, but has a number of advantages including greater flexibility in the
      writing media and the ability to use low power, inexpensive, continuous-wave
      lasers. This system writes index structures both parallel and perpendicular to
      the writing beam in different types of photopolymers, providing control over the
      feature size and shape. We demonstrate that this system can be used to create
      single-mode waveguides that are deeply embedded in the photopolymer medium.

PMID- 17228373
TI  - Improved silica-zirconia sol synthesis for fabrication of a single-mode embedded
      dielectric channel waveguide with low transmission losses.
AB  - A novel inorganic-organic hybrid silica-zirconia solgel material, which can
      generate 10 microm thick film in a single spin-coating process, has been
      developed and employed in the fabrication of an embedded dielectric channel
      waveguide on a silica buffer layer of a silicon substrate. The fabricated channel
      waveguide core had steep ridge walls, good smoothness, and high robustness, and
      the novel sol synthesis enabled a precise control of the geometrical and optical
      parameters of the embedded dielectric channel waveguide. In the 1.55 microm
      telecommunication window, the fundamental modes TE(00) and TM(00) in the embedded
      channel waveguide had low transmission losses of 0.40 +/- 0.03 dB/cm and 0.59 +/-
      0.03 dB/cm, respectively.

PMID- 17228374
TI  - Ultra-widely tunable long-period holey-fiber grating by the use of mechanical
      pressure.
AB  - We report an ultra-widely tunable long-period holey-fiber grating, which combines
      the wide-range single-mode behavior and transverse strain sensitivity of the
      holey fibers with the advantages of mechanically induced long-period fiber
      gratings. We obtain a versatile widely tunable long-period holey-fiber grating
      with attractive transmission spectral characteristics for optical communications,
      fiber-based amplifiers, and lasers. The mechanically induced long-period holey
      fiber grating shows a continuous tuning range over 500 nm, more than 12 dB depth
      notches with less than 0.75 dB out-of-band losses, and bandwidth control from 10
      to 40 nm.

PMID- 17228375
TI  - Lens axicons in oblique illumination.
AB  - Lens axicons, i.e., lenses or lens systems designed to work like axicons, can be
      a simple and inexpensive way of generating the characteristic axicon focal line.
      In the design of most lens axicons, only on-axis properties have been considered.
      We present the design of a lens axicon with improved off-axis characteristics. It
      is constructed from a singlet lens but with a double-pass feature that allows for
      a line of uniform width and a stop positioned to minimize aberrations. We perform
      off-axis analysis and experiments for this system and for another lens axicon,
      one designed for its on-axis characteristics. We conclude that the off-axis
      performance of the double-pass axicon is better than both that of an ordinary
      cone axicon and that of the other lens axicon.

PMID- 17228376
TI  - Compact system description for systems comprising a tilted plane parallel plate.
AB  - A paraxial model describing the astigmatism generated by a plane-parallel plate
      is derived. This model fits the framework of the 4x4 matrix formalism that
      Arsenault used to describe cylindrical lenses. The framework including this new
      model is used to build a compact system description of a plane-parallel plate
      combined with a cylindrical lens, from which several imaging properties are
      derived. Calculation results are compared with ray-trace simulation results and
      measurements. Both the ray-trace and the experimental results are in excellent
      agreement with the calculated results.

PMID- 17228377
TI  - Employing spectra of polycrystalline materials for the verification of optical
      constants obtained from corresponding low-symmetry single crystals.
AB  - The determination of optical constants from spectra of low-symmetry single
      crystals or from spectra stemming from unfavorable crystal faces by dispersion
      analysis is a difficult task. Besides oscillator frequencies, band positions can
      additionally depend on oscillator strength as well as on the relative orientation
      of the transition moment. Therefore the results of the analysis are highly prone
      to errors. We present an easy method to validate the oscillator data resulting
      from dispersion analysis by the comparison of measured and simulated spectra of
      randomly oriented polycrystalline materials. Depending on the crystallite size,
      either average reflectance and transmittance theory (ARTT) or average refractive
      index theory (ARIT) can be applied to model the spectra of polycrystalline
      compounds. As an alternative to ARIT, effective medium theory (EMA) can also be
      employed. However, since principal dielectric functions do not exist in the
      general triclinic case, which are needed for the application of EMA, we suggest
      using the eigenvalues of the dielectric tensor function instead. Our method for
      the verification of optical constants of single crystals is validated using
      monoclinic CuO as an example.

PMID- 17228378
TI  - Form and structure factors for impedance and reflection from periodic layers.
AB  - In an exact treatment of the Maxwell equations, we derive form and structure
      factors for reflection from periodic layers, and we show that these factors are
      significantly different from their analogs in kinematic x-ray diffraction. Quite
      generally, we show that reflection and impedance can be written precisely as the
      sum of an additive form factor and the product of a structure factor and a second
      form factor. This additive form factor does not have an analog in kinematic x-ray
      diffraction. It is demonstrated that the form factors are found by analytic
      continuation to an arbitrary wavelength of expressions for the impedance both at
      long wavelengths and at quarter wavelengths. A correction to the Bragg law
      relating fringe spacing to the total structure thickness is derived. We go beyond
      previous numerical work by deriving simple analytic exact expressions for
      reflection and impedance of periodic layers for all frequencies within the
      reflection passband, and for an arbitrary number of periods in the structure, an
      arbitrary index profile within each period, arbitrary layer thicknesses (not just
      quarter-wave layers), and for arbitrary sizes of the refractive index
      differences.

PMID- 17228379
TI  - Enhancement of diffraction efficiency and storage life of poly(vinyl chloride)
      based optical recording medium with incorporation of an electron donor.
AB  - The diffraction efficiency, sensitivity, and storage life of methylene blue
      sensitized poly(vinyl chloride) film was improved by the addition of an electron
      donor in the matrix. The addition of pyridine enhanced the diffraction efficiency
      by two times, and storage life of the gratings was increased to 2-3 days.

PMID- 17228380
TI  - Reconstruction domain compression of phase-shifting digital holograms.
AB  - Phase-shifting digital hologram compression has been mainly studied in the
      recording domain, where data possess a rather randomlike appearance, yielding
      reduced compression efficiency. We carry out the compression of such data in the
      reconstruction domain, which benefits from the spatial correlation of the data
      yielding, increased efficiency. Real holographic data are used to demonstrate the
      performance of the new approach. It is also shown that the reconstruction is not
      limited to the initially obtained view, as additional views can still be obtained
      with appropriate postprocessing.

PMID- 17228381
TI  - Fusion algorithm for poultry skin tumor detection using hyperspectral data.
AB  - We consider a feature selection method to detect skin tumors on chicken carcasses
      using hyperspectral (HS) reflectance data. Detection of chicken tumors is
      difficult because the tumors vary in size and shape; some tumors are small, early
      stage tumor spots. We make use of the fact that a chicken skin tumor consists of
      a lesion region surrounded by a region of thickened skin and that the spectral
      responses of the lesion and the thickened-skin regions of tumors are considerably
      different and train our feature selection algorithm to separately detect lesion
      regions and thickened-skin regions; we then fuse the two HS detection results to
      reduce false alarms. To the best of our knowledge, these techniques are new. Our
      forward selection and modified branch and bound algorithm is used to select a
      small number of lambda spectral features that are useful for discrimination.
      Initial results show that our method offers promise for a good tumor detection
      rate and a low false alarm rate.

PMID- 17228383
TI  - All-fiber dynamic gain equalizer based on a twisted long-period grating written
      by high-frequency CO2 laser pulses.
AB  - A novel dynamic gain equalizer for flattening Er-doped fiber amplifiers based on
      a twisted long-period fiber grating (LPFG) induced by high-frequency CO(2) laser
      pulses is reported for the first time to our knowledge. Experimental results show
      that its transverse-load sensitivity is up to 0.34 dB/(g.mm(-1)), while the twist
      ratio of the twisted LPFG is approximately 20 rad/m, which is 7 times higher than
      that of a torsion-free LPFG. In addition, it is found that the strong orientation
      dependence of the transverse-load sensitivity of the torsion-free LPFG reported
      previously has been weakened considerably. Therefore such a dynamic gain
      equalizer based on the unique transverse-load characteristics of the twisted LPFG
      provides a much larger adjustable range and makes packaging of the gain equalizer
      much easier. A demonstration has been carried out to flatten an Er-doped fiber
      amplifier to +/-0.5 dB over a 32 nm bandwidth.

PMID- 17228384
TI  - Phase error corrected 4-bit true time delay module using a cascaded 2 x 2 polymer
      waveguide switch array.
AB  - A fully integrated 4-bit true time delay device using polymer optical switches
      and waveguide delay lines is demonstrated. The fabricated device, which contains
      five 2x2 thermo-optic switches, has a maximum power consumption of 143 mW and a
      switching time less than 3 ms. The rf phase error, which is affected by the
      optical switch cross talk, is also theoretically analyzed and proved to be
      negligible by experimental results.

PMID- 17228382
TI  - Dispersion multiplexing with broadband filtering for miniature spectrometers.
AB  - We replace the traditional grating used in a dispersive spectrometer with a
      multiplex holographic grating to increase the spectral range sensed by the
      instrument. The multiplexed grating allows us to measure three different,
      overlapping spectral bands on a color digital focal plane. The detector's
      broadband color filters, along with a computational inversion algorithm, let us
      disambiguate measurements made from the three bands. The overlapping spectral
      bands allow us to measure a greater spectral bandwidth than a traditional
      spectrometer with the same sized detector. Additionally, our spectrometer uses a
      static coded aperture mask in the place of a slit. The aperture mask allows
      increased light throughput, offsetting the photon loss at the broadband filters.
      We present our proof-of-concept dispersion multiplexing spectrometer design with
      experimental measurements to verify its operation.

PMID- 17228385
TI  - Diode-side-pumped 131 W, 1319 nm single-wavelength cw Nd:YAG laser.
AB  - A diode-side-pumped high-power 1319 nm single-wavelength Nd:YAG continuous wave
      (cw) laser is described. Through reasonable coating design of the cavity mirrors,
      the 1064 nm strongest line as well as the 1338 nm one have been successfully
      suppressed. The laser output powers corresponding to four groups of different
      output couplers operating at 1319 nm single wavelength have been compared. The
      output coupler with the transmission T=5.3% has the highest output power, and a
      131 W cw output power was achieved at the pumping power of 555 W. The optical
      optical conversion efficiency is 23.6%, and the slope efficiency is 46%. The
      output power is higher than the total output power of the dual-wavelength laser
      operating at 1319 nm and 1338 nm in the experiment.

PMID- 17228386
TI  - Thermal characterization of liquid core optical ring resonator sensors.
AB  - The liquid core optical ring resonator (LCORR) has recently shown promise as a
      high-sensitivity label-free lab-on-a-chip biological-chemical sensor. We
      investigate experimentally and theoretically the temperature dependence of the
      LCORR to establish a noise baseline, which will enable us to implement a
      temperature stabilization mechanism to reduce the thermally induced noise and to
      improve the sensor detection limit. Our studies involve analysis of the thermo
      optic and thermomechanical effects of fused silica and aluminosilicate glass as
      they impact LCORR performance. Both thick-walled and thin-walled LCORRs are
      investigated to elucidate the contribution of water in the core to the thermal
      response of the LCORRs. Theoretical calculations based on Mie theory are used to
      verify the experimental observations.

PMID- 17228387
TI  - Optimal coupling of light from a cylindrical scintillator into an optical fiber.
AB  - Radiation dose measurements based on scintillator detection are conveniently made
      by coupling the light from the scintillator into an optical fiber. The low light
      levels involved typically require sensitive photodetectors, so it is advantageous
      to increase the available signal by optimizing the optical coupling efficiency
      between the scintillator and optical fiber. We model this process using geometric
      optics and finite-element ray tracing to determine the features that maximize the
      amount of light coupled to an optical fiber from a cylindrical scintillator. We
      also address whether the coupling can be improved by using an intermediate
      optical element such as a lens, and we provide a means for calculating its
      required optical properties for a given geometry.

PMID- 17228388
TI  - Dual-trap technique for reduction of low-frequency noise in force measuring
      optical tweezers.
AB  - High-resolution long-time force measurements by optical tweezers are often
      limited by low-frequency (1/f) noise. A dual-trap technique is presented that can
      reduce such noise in the force signal. It incorporates a second trap (a reference
      trap) that probes the noise in the system and it is based upon the assumption
      that the low-frequency parts of the noise from the two traps are correlated. A
      subtraction of the low-frequency signal from the reference trap from the signal
      from the force measuring trap will therefore yield a net signal that is
      significantly less influenced by noise. It is shown that this dual-trap technique
      can reduce the noise in the force signal up to 60% depending on detection
      bandwidth.

PMID- 17228389
TI  - Laser-fiber system for ablation of intraocular tissue using the fourth harmonic
      of a pulsed Nd:YAG laser.
AB  - We report on a method for delivering high fluence pulsed 266 nm laser radiation
      to the target tissue via an optical fiber. The fourth harmonic of a Nd:YAG laser
      was concentrated using a hollow glass taper and launched into an optical fiber.
      Fluences of up to 2 J/cm(2) were routinely output at the tapered optical fiber
      tip. The maximum fluence generated before failure of the optical fiber was
      between 3.5 and 8 J/cm(2). Ablation of ocular tissue was demonstrated using
      fluences of 1.0 and 0.4 J/cm(2). The delivery system has the potential for use in
      intraocular surgical procedures.

PMID- 17228390
TI  - Stabilization of an optical microscope to 0.1 nm in three dimensions.
AB  - Mechanical drift is a long-standing problem in optical microscopy that occurs in
      all three dimensions. This drift increasingly limits the resolution of advanced
      surface-coupled, single-molecule experiments. We overcame this drift and achieved
      atomic-scale stabilization (0.1 nm) of an optical microscope in 3D. This was
      accomplished by measuring the position of a fiducial mark coupled to the
      microscope cover slip using back-focal-plane (BFP) detection and correcting for
      the drift using a piezoelectric stage. Several significant factors contributed to
      this experimental realization, including (i) dramatically reducing the low
      frequency noise in BFP detection, (ii) increasing the sensitivity of BFP
      detection to vertical motion, and (iii) fabricating a regular array of nanometer
      sized fiducial marks that were firmly coupled to the cover slip. With these
      improvements, we achieved short-term (1 s) stabilities of 0.11, 0.10, and 0.09 nm
      (rms) and long-term (100 s) stabilities of 0.17, 0.12, and 0.35 nm (rms) in x, y,
      and z, respectively, as measured by an independent detection laser.

PMID- 17228395
TI  - Vegetable protein lowers blood pressure.

PMID- 17228394
TI  - Antidepressants plus exercise an antidote to depression.

PMID- 17228396
TI  - Help for the sleep-deprived. If counting sheep doesn't work for you, there are
      other successful strategies.

PMID- 17228397
TI  - A toast to your health.

PMID- 17228398
TI  - Uterine cancer could be harbinger of other cancers. An inherited mutation--Lynch
      syndrome--may lead to higher risk.

PMID- 17228399
TI  - I survived a heart attack five years ago and haven't had any serious symptoms
      since then. What are the odds I'll have another heart attack? I've tried to do
      everything my doctors suggest--taking medicines, eating less fat in my diet and
      not smoking.

PMID- 17228400
TI  - I am currently taking methotrexate for my rheumatoid arthritis, but I've heard
      that it doesn't interact well with penicillin. Are there any other drugs I should
      not take while taking methotrexate?

PMID- 17228401
TI  - I've had one bout with shingles. Can I get it again? Can I prevent it?

PMID- 17228402
TI  - Infection fighters. Hepatitis C--some types are worse than others.

PMID- 17228403
TI  - Vaccines. Vaccines as therapy.

PMID- 17228404
TI  - Side effects and complications. Can statins help reverse body-shape changes in
      men?

PMID- 17228406
TI  - [Lies and Latin].

PMID- 17228405
TI  - A modeling study of notch noise responses of type III units in the gerbil dorsal
      cochlear nucleus.
AB  - A computational model of the neural circuitry of the gerbil dorsal cochlear
      nucleus (DCN), based on the MacGregor's neuromime model, was used to simulate
      type III unit (P-cell) responses to notch noise stimuli. The DCN patch model is
      based on a previous computational model of the cat DCN [Hancock, K. E., and H. F.
      Voigt. Ann. Biomed. Eng. 27:73-87, 1999]. According to the experimental study of
      Parsons et al. [Ann. Biomed. Eng. 29:887-896, 2001], the responses of gerbil DCN
      type III units to notch noise stimuli are similar to those of cat DCN type IV
      units, which are thought to be spectral notch detectors. This suggests that type
      III units in the gerbil DCN may serve as spectral notch detectors. In this
      modeling study, a simplified notch noise response plot--spike discharge rate vs.
      notch cutoff frequency plot--was used to compare model responses to the
      experimental results. Parameter estimation and sensitivity analysis of three
      connection parameters within the DCN patch have been studied and shows the model
      is robust, providing reasonable fits to the experimental data from 14 of 15 type
      III units examined.

PMID- 17228407
TI  - [Sex differences in sports performance].

PMID- 17228408
TI  - [Eating for top performance in sports?].

PMID- 17228410
TI  - [Mountaineering--crazy or genial?].

PMID- 17228409
TI  - [Red card--aggression in sports].

PMID- 17228411
TI  - [How can human beings perform in the outer space? Exercise in space].

PMID- 17228412
TI  - [Diving--an extreme sport?].

PMID- 17228413
TI  - [Tour de France--what heart can pull through it?].

PMID- 17228415
TI  - [Are elite soccer players more often injured?].

PMID- 17228414
TI  - New guidelines on malaria prevention: A summary.
AB  - Travellers to many tropical areas remain at risk of contracting malaria.
      Resistance of malaria parasites to a number of drugs continues to increase in
      degree and distribution, so that some older, trusted prophylactic drugs, such as
      chloroquine, are no longer useful in some parts of the world. Despite the
      introduction of new drugs and the reduction of malaria risk in some areas, such
      as parts of India, the number of people travelling continues to increase and
      malaria reports in the UK are not decreasing. New updated prevention guidelines
      from the Health Protection Agency Advisory Committee on Malaria Prevention (ACMP)
      in UK travellers (Chiodini P, Hill D, Lalloo D, Lea G, Walker E, Whitty C, et al.
      Guidelines for malaria prevention in travellers from the United Kingdom. London:
      Health Protection Agency; January 2007. Available from:
      http://www.hpa.org.uk/infections/topics_az/malaria/default.htm) aim to raise
      awareness of the risks of malaria and help UK travel health advisors in giving
      malaria prevention advice to all those who need it. Together with the ACMP
      malaria treatment guidelines it is hoped that the risk of illness and death from
      malaria in UK travellers can be reduced. This article summarises the new ACMP
      malaria prevention guidelines.

PMID- 17228416
TI  - [Can asthma be induced by elite sports performance?].

PMID- 17228417
TI  - [Long term musculoskeletal effects of elite sports performance].

PMID- 17228418
TI  - [The death and the death certificates].

PMID- 17228419
TI  - [Death certificates--we have created vigorous solution].

PMID- 17228420
TI  - Protests in China over suspicions of a pay-or-die policy.

PMID- 17228421
TI  - Child death in Germany sparks health-policy review.

PMID- 17228422
TI  - Obesity and migraine: a population study.

PMID- 17228423
TI  - Abstracts of the International Continence Society 36th Annual Meeting,
      Christchurch, New Zealand, 27 November-1 December 2006.

PMID- 17228424
TI  - Abstracts of the 14th International Symposium on Bioluminescence and
      Chemiluminescence.

PMID- 17228425
TI  - Bioluminescence, chemiluminescence and fluorescence imaging, January 2004-May
      2006 literature.

PMID- 17228427
TI  - Reduce your credit card processing costs.

PMID- 17228426
TI  - Effects of organophosphate compounds on a soil protist, Colpoda inflata
      (Ciliophora, Colpodidae).
AB  - Many investigations on protists indicate that they play an important role in
      agricultural soils. We have tested the effects of three organophosphate (OP)
      pesticides, basudin, cidial, and fenix, on the soil ciliate Colpoda inflata, and
      examined its viability, fission rate, ability to excyst and extrude macronuclear
      chromatin into cytoplasm. Exposure to these OPs caused a dose-dependent effect on
      cell viability, and significantly reduced the mean fission rate at a
      concentration of 1/10(5) v/v. After exposure of resting cysts to 1/10(5) v/v or
      1/10(6) v/v concentrations of basudin or cidial, the number of excysted cells was
      significantly lower than that of the controls. Conversely, exposure to a 1/10(5)
      v/v fenix concentration did not affect excystment and exposure to 1/10(6) v/v was
      found to promote excystment. Moreover, exposure to these OPs (1/10(4) v/v or
      1/10(5) v/v) interferred with the ability to extrude macronuclear chromatin. The
      median lethal concentration in 60 min for each OPs tested was at least a hundred
      times lower than the doses recommended by the manufacturer. Finally, as the
      inhibition of cholinesterase (ChE) activity is the first target of OPs, the
      presence of ChE activity was checked in C. inflata. Three ChE activities were
      found, hydrolyzing the substrates acetyl-beta-methyl thiocholine iodide,
      propionyl thiocholine iodide and butyryl thiocholine iodide, that appeared to be
      very low and not inhibited by OP-exposure.

PMID- 17228428
TI  - Overtime and timekeeping: what are the rules?

PMID- 17228429
TI  - Oral pathology quiz # 53. Case number 2. Lymphoma.

PMID- 17228430
TI  - Oral pathology quiz # 53. Case number 3. Traumatic eosinophilic ulcer.

PMID- 17228431
TI  - Oral pathology quiz # 53. Case number 4. Ameloblastoma.

PMID- 17228432
TI  - Terminally ill patient's experience still haunts this hospice nurse.

PMID- 17228433
TI  - Nurses reflect on how PTSD affects the lives of many.

PMID- 17228435
TI  - Saved by a sliver.

PMID- 17228436
TI  - [Melatonin: physiological and pathophysiological aspects and possible
      applications].

PMID- 17228437
TI  - [End-of-life decisions in seriously ill patients: the position of intensive care
      nurses].

PMID- 17228438
TI  - Perimenopause, hormones, and midlife health. Hormone researchers are shifting
      some of their attention from menopause to the years that precede it.

PMID- 17228439
TI  - Fatty fish linked to lower kidney cancer risk in women.

PMID- 17228440
TI  - Recognizing the mind-skin connection. Some skin conditions have a psychological
      dimension that may need to be addressed, too.

PMID- 17228441
TI  - Big toe got you down?  It may be hallux rigidus. A stiff and painful big toe can
      knock you off your feet. Here's what you can do about it.

PMID- 17228442
TI  - By the way, doctor. I read that spirulina is the next wonder vitamin. What can
      you tell me about it?

PMID- 17228444
TI  - APTIMA assay approved for HIV testing.

PMID- 17228443
TI  - Updated DHHS treatment guidelines.

PMID- 17228445
TI  - Antiretroviral rounds. A patient with multiple resistance mutations and a history
      of nonadherence.

PMID- 17228446
TI  - Meeting report. Report from ICAAC.

PMID- 17228447
TI  - New HIV drugs needed for the next decade.

PMID- 17228448
TI  - The state of access to Kaletra.

PMID- 17228449
TI  - World CAB meets with Gilead.

PMID- 17228450
TI  - Optimizing antiretroviral therapy for HCV coinfected people.

PMID- 17228451
TI  - Path of least resistance. New drug development guidance needed from FDA.

PMID- 17228452
TI  - Report from the 2nd International Workshop on HIV and Hepatitis Co-Infection,
      January 12-14, 2006, Amsterdam, Netherlands. Risk factors for liver damage from
      HAART.

PMID- 17228453
TI  - Report from the 2nd International Workshop on HIV and Hepatitis Co-Infection,
      January 12-14, 2006, Amsterdam, Netherlands.  Early treatment of sexually
      transmitted hepatitis C.

PMID- 17228454
TI  - Report from the 2nd International Workshop on HIV and Hepatitis Co-Infection,
      January 12-14, 2006, Amsterdam, Netherlands.  Longer is better for genotype 3
      treatment.

PMID- 17228455
TI  - Report from the 2nd International Workshop on HIV and Hepatitis Co-Infection,
      January 12-14, 2006, Amsterdam, Netherlands.  Tenofovir or adefovir for hepatitis
      B.

PMID- 17228456
TI  - Co-infections. Faster fibrosis with hepatitis C and HIV.

PMID- 17228457
TI  - Co-infections. Fighting fatigue and depression in HCV/HIV co-infection.

PMID- 17228458
TI  - Co-infections. Reducing risk form severe liver injury.

PMID- 17228459
TI  - Vaccines. From Brazil and France: a vaccine against HIV may lower viral load.

PMID- 17228460
TI  - Vaccines. From Israel: a T-cell vaccine.

PMID- 17228461
TI  - Vaccines. Can vaccines against HPV work in PHAs?

PMID- 17228462
TI  - Complications and side effects. Alberta clinic saves lives but faces new
      challenges.

PMID- 17228463
TI  - Complications and side effects. French researchers study bone disease.

PMID- 17228464
TI  - Addictions. Crystal meth research.

PMID- 17228465
TI  - Addictions.  Can an anti-seizure drug assist recovery from cocaine and crystal
      meth addiction?

PMID- 17228466
TI  - Immune boosters. Clues to long-term survival may lie in CD91.

PMID- 17228467
TI  - Wasting. Anabolic steroid helps women gain weight.

PMID- 17228468
TI  - Complications and side effects. Is it age or AIDS?

PMID- 17228469
TI  - Complications and side effects. Comparing the safety of statins.

PMID- 17228470
TI  - Complications and side effects. Health Canada warns about statin side effects.

PMID- 17228471
TI  - Drug interactions. Rosiglitazone and anti-HIV agents.

PMID- 17228472
TI  - Complications and side effects. Concerns about statins.

PMID- 17228473
TI  - Anti-HIV agents. Still searching for a cure.

PMID- 17228474
TI  - Anti-HIV agents. Overcoming barriers to a cure.

PMID- 17228475
TI  - Anti-HIV agents. Can valproic acid help flush HIV from hiding?

PMID- 17228477
TI  - Anti-HIV agents. Canadian trial of valproic acid.

PMID- 17228476
TI  - Anti-HIV agents. Valproic acid and HIV eradication--many questions remain.

PMID- 17228478
TI  - Global. Malnutrition link to HIV, AIDS focus at conference.

PMID- 17228479
TI  - Gates makes record contribution to Global Fund.

PMID- 17228480
TI  - Disclosure. Malpractice charges against attorney over HIV test dismissed.

PMID- 17228481
TI  - Global. 7 GI countries derided for failing to meet AIDS goals.

PMID- 17228482
TI  - Study weakens link between HIV prevalence and poverty.

PMID- 17228483
TI  - Exposure. Transmission of HIV unnecessary to uphold conviction.

PMID- 17228484
TI  - Prisons. HIV-positive prisoner's claim of care denial is dismissed.

PMID- 17228485
TI  - Exposure. Miranda challenge fails for HIV-positive child sex abuser.

PMID- 17228486
TI  - Global. WHO updates AIDS statistics at international conference.

PMID- 17228489
TI  - [Mechanisms for countering plague in modern China: the examples of Yunnan,
      Guangdong, and Fujian provinces].

PMID- 17228488
TI  - [The Ljubljana doctors: specialists around 1900].

PMID- 17228490
TI  - Bibliography. Current World Literature. Large intestine.

PMID- 17228487
TI  - Statin therapy in cardiovascular diseases other than atherosclerosis.
AB  - Statins are drugs that inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)
      reductase, thereby blocking the synthesis of cholesterol. Since being discovered
      in Japan in the mid 1970s, statins have been widely used to lower low-density
      lipoprotein cholesterol. However, analysis of cardiovascular research has
      revealed other important effects beyond changes in lipid parameters, referred to
      as pleiotropic effects. This paper focuses on the effects of statins as anti
      ischemic agents with improvement in endothelial function, along with studies on
      valvular aortic stenosis, atrial fibrillation, heart failure, peripheral arterial
      disease, and cancer. As the evolution of statin research continues, there appear
      to be new potential benefits from statins to be found in many facets of
      cardiovascular disease.

PMID- 17228491
TI  - Intraluminal metastasis at the colostomy site after Hartmann's procedure for
      obstructive rectal cancer.

PMID- 17228492
TI  - [Throw off the population-determinism halo: also, on the course of thought and
      methods in historical population research].

PMID- 17228493
TI  - An unusual retrorectal tumour in adults: the teratoma.

PMID- 17228494
TI  - [Athletic and para-athletic associations in Marseilles before 1901].

PMID- 17228495
TI  - [The beginnings of athletic camaraderie in Var and the 1 July 1901 law].

PMID- 17228496
TI  - [Fragments and body unity: questions and artistic opinions of neoclassical and
      realist painters in France in the first half of the 19th century].

PMID- 17228497
TI  - [The incommensurability of theories: a historical case for debate].

PMID- 17228499
TI  - "Atar oun kai" in Galen and his predecessors.

PMID- 17228498
TI  - [The human body as a factor in Scandinavian democracy].

PMID- 17228500
TI  - [The Arabic translation of Galen's De locis affectis].
AB  - The article concerns the Arabic translation of this tract in found in the works
      of Hubaish ibn al-Hasan Al-acsam in connection with an earlier Syriac translation
      of Hunain ibn Ishaq which is now lost.

PMID- 17228501
TI  - [With regard to Alcmaeon and Hippocrates].

PMID- 17228502
TI  - [Wine and women: an overlooked passage in the Hippocratic corpus].
AB  - A passage taken from the Hippocratic Corpus states that at the beginning of
      pregnancy women say that they do not like the taste of wine. This passage should
      be added to evidence about wine drinking by women in Classical Greece. It shows
      that, contrary to previous opinion, women drank wine when they were in good
      health and corresponds with the notion that it was often prescribed by physicians
      in order to cure illness.

PMID- 17228503
TI  - Practical ethics. Doc dilemma.

PMID- 17228504
TI  - Legal. In the crosshair.

PMID- 17228505
TI  - What do I do now, coach? What to do when your professor says you have a
      publishable manuscript.

PMID- 17228506
TI  - Children's life transition following sexual abuse.
AB  - The life transition of children 6 to 13 years old was studied for 1 to 3 years
      following sexual abuse. Data included transcripts from in-depth interviews about
      the children's daily living experiences and drawings were analyzed using the
      ADOPT analysis procedure. Implications for nursing include the use of drawings as
      a research technique and the effectiveness of strategies used by participants to
      manage the aftermath of the trauma.

PMID- 17228507
TI  - An evaluation of perceived education and training needs of staff nurses and care
      officers.
AB  - This study was carried out to ascertain the specific education and training needs
      of nursing and care officer staff working at the Central Mental Hospital (CMH) in
      Dublin, Ireland, which provides national forensic psychiatric services. This is
      the first time an education and training needs analysis was conducted for all
      nursing and care officer staff.

PMID- 17228508
TI  - Intimate partner violence screening and treatment: the importance of nursing
      caring behaviors.
AB  - Intimate partner violence (IPV) is a major health concern worldwide. It is the
      primary cause of traumatic injury to women and one of the leading causes of death
      for pregnant women. Emergency department (ED) nurses are in a unique position to
      identify, IPV victims, however, many hospital EDs do not perform routine
      screenings. This article reviews the literature associated with barriers to
      screening for IPV and victim's experiences when seeking care in an ED following
      IPV.

PMID- 17228509
TI  - Research and evaluation of clinical nurse mentoring: implications for the
      forensic context.
AB  - The impact of mentoring programmes was examined in this extensive literature
      review. The effectiveness of such programs was considered for both the general
      clinical nursing and clinical forensic nursing environments. No literature
      discussing clinical nurse mentoring within forensic settings was discovered
      during the review, thus implications for this unique context are drawn from the
      current available literature.

PMID- 17228510
TI  - Considering culture in understanding interpersonal violence.
AB  - Interpersonal violence is a global phenomenon. Forensic nurses should seek
      cultural competency to help them better understand the relationship between
      culture and interpersonal violence.

PMID- 17228511
TI  - Integrating prevention into practice: an introduction to sexual violence primary
      prevention literature.
AB  - IAFN received a grant in 2005 from the Centers for Disease Control and Prevention
      to help members integrate primary sexual violence prevention into practice. This
      column reviews some of the online literature available and reframes the concept
      of prevention as it relates to forensic nursing.

PMID- 17228512
TI  - Cause of death among elder homicide victims: a 10-year medical examiner review.
AB  - A study of elderly homicide victims brought to a Pennsylvania medical examiner's
      office reveals interesting findings about cause of death.

PMID- 17228513
TI  - [Surgery of primary hyperparathyroidism].
AB  - Surgery of primary hyperparathyroidism. Primary hyperparathyroidism is usually
      caused by a single parathyroid adenoma, rarely by multiple adenomas or
      hyperplasia and in 1-2% of cases by carcinoma. The definitive cure of the disease
      can be achieved only by surgical means. Unfortunately, only 10% of expected cases
      based on the number of population are diagnosed in Hungary. The main reason is
      that the disease has no specific symptoms and it causes only a few cases present
      with clinical entities such as nephrolithiasis, osteoporosis-osteopenia,
      pancreatitis, hypertension, peptic ulcer disease, depression, etc. The clue to
      the diagnosis of primary hyperparathyroidism is usually the laboratory result of
      hypercalcemia and in order to this aim the measurement of serum Ca would be an
      obligatory part of routine laboratory investigation in Hungary. The diagnosis of
      primary hyperparathyroidism rests on the laboratory confirmation of increased
      serum calcium and inappropriately elevated intact parathyroid hormone
      concentrations. If surgical intervention is planned, cervical ultrasonography and
      parathyroid-scintigraphy are indicated for the exact localization of
      hyperfunctioning parathyroid gland(s). CT and/or MRI are usually not necessary,
      except in cases of previous neck operation. The operation must be performed by
      surgeon skilled in parathyroid surgery. The surgical success can be assessed
      intraoperatively by the use of a gamma probe or by intraoperative measurement of
      parathyroid hormone concentrations in the serum or in the removed tissue(s).
      Support of these procedures is recommended. Although many recent publications
      deal with the minimal invasive methods of parathyroidectomy, the cost
      effectiveness of these newer techniques are controversial.

PMID- 17228514
TI  - [Sexually transmitted infections in the XXI century].
AB  - Sexually transmitted infections in the XXI century. The most important
      measurements in the management of sexually transmitted diseases are discussed.
      Course and incidence of classical venereal diseases, especially that of syphilis
      are detailed. In 2004 the incidence of early infectious syphilis significantly
      increased and it is emphasized that this tendency can be observed also in 2005.
      Differential diagnostic issues of male and female urogenital diseases with
      discharge are reviewed, and problems of STDs of viral origin (genital herpes,
      genital warts, HIV infection) are briefly discussed. The importance of careful
      and specific microbiological diagnostics in the management of patients with
      venereal diseases and other sexually transmitted infections is emphasized.

PMID- 17228516
TI  - [Kinesiological examinations and cutaneous EMG with integrated 3D UH system in
      adolescent idiopathic scoliosis (type: King 1-13)].
AB  - The origin of idiopathic scoliosis is unknown however there are many hypothesis.
      One of them is the biomechanic theory. The cause of spreading the cutaneous EMG
      is: noninvasive, and can be used during movements. AIM: Authors find by CMS
      system in their earlier examination, that range of right rotation (of idiopathic
      scoliotic spine King 1-3 type) increased. They supposed that the change of spine
      motion cause change in muscle functions also. To verify this hypothesis above:
      they made examinations by cutaneous EMG parallel to the kinesiological
      examinations.(CMS system, 3D ultrasound movement analyse). METHOD: Kinesiological
      examinations on 25 girls with idiopathic scoliosis (King 1-3) were performed
      parallel to examining cutaneous bilateral EMG on eight spinal close muscles.
      RESULT AND CONCLUSION: They established that beside functional movements there
      were a so called non-functional movement however this component were small.
      Analysing the results, they used phase and amplitude analysis. In the course of
      phase- and amplitude analysis, they took only those changes into consideration
      which were significantly different of the two side compared with to healty
      groups. In the course of phase- and amplitude analysis, they found: that muscle
      erector spine was weakened in strength and decreased in movement range. They
      intend to make clear the etiology part in idiopathic scoliosis.

PMID- 17228515
TI  - [Retrospective analysis of the effect of vinpocetine infusion in ophthalmologic
      disorders].
AB  - Retrospective analysis of the effect of vinpocetine infusion in ophthalmologic
      disorders. The authors retrospectively examined the effect of vinpocetine
      infusion on various ophthalmological disorders. Based on the data of 280 patients
      they concluded that vinpocetine infusion has beneficial effects in numerous
      ophthalmologic disorders of vision and visual field. There was a clear difference
      regarding the response to treatment. Best results were achieved in diseases
      characterized by sclerosis, hypertonia and macular degeneration. The improvement
      was modest or progression was slowed in patients with nervus opticus ischaemia,
      glaucoma and myopia. These results are in accordance with the literature data.
      The beneficial effect of vinpocetine can be explained by the fact that the
      vessels of the eye are in direct connection with the cerebral circulation and
      hereby the circulation improving effect of vinpocetine could be effective. The
      neuronal effects of vinpocetine could also play a role at least in two ways. On
      the one hand by the direct effect exerted on the cells of retina (these cells are
      related to the neurons), and on the other hand by the improvement of the
      circulation and metabolism of the secondary visual cortex found in the occipital
      lobe (this effect is proved by PET studies).

PMID- 17228517
TI  - [Cripples at the medieval hospital of Batmonostor, Hungary--archeological
      findings].
AB  - Cripples from the medieval hospital of Batmonostor, Hungary. People with
      disabilities were generally burdened with a painful fate in ancient times,
      however in the hospitals was no effective therapy. The hospital of Batmonostor
      was founded at late 13th century, The authors examine by morphological,
      radiological and histological methods 426 complete skeletons excavated from
      medieval (14th-15th century) cemetery of Batmonostor (Hungary). Among them 30
      cases (7.1%) of bony ankylosis, (24 cases on lower limb and 6 cases on upper
      limb) was found. Sacroiliac ankylosis 3 cases, Bechterew's spondylitis
      ankylopoetica 1 case was seen. Spondylitis tuberculosa and malum Potti 4 cases,
      and hunchback with other aetiology 2 cases was detected. Beside the cases with
      ankylosis severe posttraumatic osteomyelitis (7 cases), primary malignant bone
      tumors (2 cases) and an osteoplastic metastatic tumors (probably prostata
      carcinoma) was diagnosed. Paleopathologic study of the physically disabled may
      yield information and insight on the prevalence of crippling disorders. The
      authors hypothetize, that crippled persons lived in the hospital until their
      deaths.

PMID- 17228518
TI  - [Malignant gastrointestinal stromal tumor arising in a duodenal diverticulum].
AB  - Malignant gastrointestinal stromal tumor arising in a duodenal diverticulum. The
      authors describe the case of a 74-year-old male patient who was operated on for a
      GIST found in a large duodenal diverticulum, co-using gastrointestinal bleeding.
      This diverticulum--including the tumor--was removed by resection the distal part
      of the stomach and proximal third of duodenum. The histology revealed malignant
      gastrointestinal stromal tumor (GIST). 6 months after the operation he remained
      tumor free according to the control examinations. On the basis of new pathologic
      classification we summarise the signs, the diagnostic and therapeutic
      possibilities and the histologic characteristics of gastrointestinal stromal
      tumors.

PMID- 17228519
TI  - Genetic polymorphisms of human ABC transporter ABCG2: development of the standard
      method for functional validation of SNPs by using the Flp recombinase system.
AB  - The vector-mediated introduction of cDNA into mammalian cells by calcium
      phosphate co-precipitation or permeation with lipofectamine is widely used for
      the integration of cDNA into genomic DNA. However, integration of cDNA into the
      host's chromosomal DNA occurs randomly at unpredictable sites, and the number of
      integrated recombinant DNAs is not controllable. To investigate the effect of
      genetic polymorphisms of ABCG2 on the protein expression and the drug resistance
      profile, we developed the Flp-In method to integrate one single copy of ABCG2
      variant-cDNA into FRT-tagged genomic DNA. More than 20 metaphase spreads were
      examined for both fluorescence in situ hybridization (FISH) mapping and
      multicolor-FISH analysis, and it has been revealed that ABCG2 cDNA was
      incorporated into the telomeric region of the short arm on one of chromosomes 12
      in Flp-In-293 cells. Based on the currently available SNP data for human ABCG2,
      we have created a total of seven variants by site-directed mutagenesis and stably
      expressed them in Flp-In-293 cells. While mRNAs of those integrated ABCG2
      variants and wild type were evenly expressed in Flp-In-293 cells, the protein
      expression levels of F208S and S441N variants were found to be markedly low. It
      is suggested that the protein instability due to enhanced degradation resulted in
      the low levels of their protein expression. Thus, the Flp recombinase system
      would provide a useful tool to validate the effect of nonsynonymous SNPs on the
      protein stability and post-translational modification of ABCG2.

PMID- 17228520
TI  - Inhibition of tumor angiogenesis by Brahma Rasayana (BR).
AB  - The current therapy for prostate cancer includes radical prostatectomy, radiation
      therapy and hormonal ablation. Chemotherapy also provides beneficial results for
      some patients with advanced prostate cancer but with several harmful side
      effects. Hence there is a need to identify and develop alternate therapies, which
      can reduce the disease progression with minimal or few side effects. Earlier
      studies from our laboratory have shown that a Polyherbal mixture, Brahma Rasayna
      (BR) rich in anti-oxidant principles has a potential to be an anti-tumor agent.
      BR treatment of MAT-LyLu cell inoculated Copenhagen rats resulted in a decrease
      of palpable tumor incidence, delay in tumor occurrence and lower mean tumor
      volumes. Also, a significant reduction in tumor weight and lung metastasis was
      observed in BR treated animals in comparison to untreated controls. In the
      present study, we focused to examine the effect of BR on angiogenesis and
      regulation of molecular markers involved in angiogenesis using in-vivo and in
      vitro models. BR treatment showed a significant reduction in Factor VIII
      expression compared to control indicating reduced angiogenesis. BR treated tumor
      specimens showed a decrease in the pro-angiogenic factors like VEGF, MMP-9 and
      MMP-2. Methanolic extract of BR was found to inhibit the proliferation, tube
      formation, cell migration and attachment of HUVEC on matrigel in a dose dependant
      manner. These findings suggest the possible mechanism(s) of action of BR in the
      reduction of tumor growth and metastatic spread.

PMID- 17228521
TI  - Cytotoxicity of different selective serotonin reuptake inhibitors (SSRIs) against
      cancer cells.
AB  - Cell membrane ion transporters expression and activity are altered in cancer
      cells and these phenotypic alterations offer potential targets for cancer
      therapies. Among the therapeutic agents affecting cell membrane transporters,
      serotonin reuptake inhibitors (SSRIs) have been shown to have anticancer
      potential. In this work, we have compared two SSRIs, one very specific for
      serotonin reuptake transporters (paroxetine) and another which also inhibit
      norepinephrine and dopamine transporters (venlafaxine), for their ability to
      counteract growth of various murine and human cancer cell lines. We found that
      paroxetine has cytotoxic activity against tumor cells, both of murine or human
      origin in the micromolar concentration range, whereas venlafaxine has not. A
      neurotransmitter receptor mediated mechanism of action appears thus unlikely for
      SSRIs cytotoxicity on cancer cells. With ranges of SSRIs cytotoxicity on cancer
      cells defined, limits in their possible applicability in cancer therapy is
      discussed.

PMID- 17228522
TI  - Cytotoxic effects of leaf, stem and root extracts of Nerium oleander on leukemia
      cell lines and role of the p-glycoprotein in this effect.
AB  - Nerium oleander (No), is a toxic plant. In recent studies, it was determined that
      the extracts of this plant are effective to treat some types of cancer, but these
      studies are limited and do not include human leukemia. In the present study,
      firstly we aimed to investigate in vitro the cytotoxic effects of No on the HL60
      and K562 leukemia cell lines. The cells were incubated with six different
      concentrations of each three extracts. MTT assay was employed as a cytotoxicity
      test. It was observed that concentrations of 1000, 500 and 50 microg/ml from each
      extract possess marked antileukemic effects. No leaf and root extracts were seen
      to be more cytotoxic than the stem extract according to LC50. Secondly, in order
      to understand the role of P-gp in cytotoxicity, P-gp levels of K562 resistant and
      sensitive cells were measured by flow cytometry before treatment extracts, and
      then, the cells were incubated with No leaf, stem and root extracts in 500
      microg/ml concentrations overnight. After incubation, measurements showed
      decreased levels of P-gp in the cells. Hence, it is possible to think contributes
      to their cytotoxic effects that inhibiting of the P-gp pump by No extracts on
      leukemia cell lines.

PMID- 17228523
TI  - Genetic reduction of matriptase-1 expression is associated with a reduction in
      the aggressive phenotype of prostate cancer cells in vitro and in vivo.
AB  - PURPOSE: Matriptase-1 has been implicated as playing an important role in various
      types of cancer progression through many different cancer related pathways. In
      the current study we assessed the efficacy of targeting matriptase-1 using
      ribozyme technology in vitro and in vivo. EXPERIMENTAL DESIGN: Matriptase-1
      expression was reduced in the PC-3 and DU-145 cell line using hammerhead ribozyme
      transgenes. In vitro assays were set up to assess changes in growth, invasion,
      adhesion and migration in these cells. In vivo tumour development model was also
      used to examine the efficacy of targeting matriptase-1 in a living environment.
      RESULTS: The in vitro results suggest an overall reduction in the aggressive
      nature of the two cell lines (PC-3 and DU-145) when matriptase-1 levels are
      reduced, with properties such as growth, invasiveness and migration all being
      reduced (in most cases a greater than 50% reduction in migration and invasion
      compared to the control was observed), though strangely an increase in adhesion
      is seen in the PC-3 knockout. The in vitro data is strongly backed up by the
      results of the in vivo work which demonstrates matriptase-1 deficient cells have
      a substantially reduced ability to grow and develop in vivo compared to control
      cells when explanted into nude mice, with significant differences in growth and
      development (P < or = 0.05) being seen after 7 days, and highly significant
      differences (p < or = 0.001) after 15 days. CONCLUSIONS: Together this data
      strongly implicates matriptase-1 as playing a vital role in the aggressive nature
      and progression of prostate cancer.

PMID- 17228524
TI  - Genome-wide cDNA microarray screening of genes related to the benefits of
      paclitaxel and irinotecan chemotherapy in patients with advanced non-small cell
      lung cancer.
AB  - Previous studies have demonstrated that not only the benefits but also the
      toxicities of chemotherapy can be predicted by cDNA microarray analysis of tumor
      specimens obtained before chemotherapy against non-small cell lung cancer
      (NSCLC). We conducted a study of cDNA microarray analysis to determine whether
      the gene expression in peripheral blood taken from patients prior to chemotherapy
      were correlated with the outcome of chemotherapy with paclitaxel (Pac) and
      irinotecan (CPT) against advanced NSCLC. Thirty-one patients with stage IIIB or
      IV NSCLC were treated with CPT at 60 mg/m2 and Pac at 160 mg/m2 every 2 weeks.
      Seventeen of 31 patients achieved PR and the overall RR was 54.8%. The median
      survival time was 426 days and the 1-year survival rate was 58.1%. The expression
      levels of 1176 genes were analyzed in 31 patients with the AtlasTM Human Cancer
      1.2 Array. Stepwise multivariate analysis revealed that the genes encoding
      protein phosphatase, IL-1alpha and IgA were independent predictive factors for
      chemosensitivity. Stepwise regression analysis revealed that the thyrotropin
      releasing hormone receptor and alkylation repair genes were independent
      prognostic factors. In conclusion, the expression of certain genes was able to
      predict the benefits of this Pac and CPT chemotherapy regimen.

PMID- 17228525
TI  - Cancer chronomics I. Origins of timed cancer treatment: early marker rhythm
      guided individualized chronochemotherapy.
AB  - A 21-year old patient who presented in 1973 with a rare and highly malignant
      ovarian endodermal sinus tumor with spillage into the peritoneal cavity is alive
      and well today after receiving chronochemotherapy. During the first four courses
      of treatment, medications were given at different circadian stages. Complete
      blood counts and marker variables such as mood, vigor, nausea, and temperature
      were monitored around the clock and analyzed by cosinor to seek times of highest
      tolerance. Remaining treatment courses were administered at a time corresponding
      to the patient's best drug tolerance, rather than extrapolating the timing of
      optimal cyclophosphamide administration from also-implemented parallel laboratory
      studies on mice. Notwithstanding remaining hurdles in bringing chronochemotherapy
      to the clinic for routine care, merits of marker rhythm-guided chronotherapy
      documented in this and other case reports have led to the doubling of the two
      year disease-free survival of patients with large perioral tumors in a clinical
      trial.

PMID- 17228526
TI  - Cancer chronomics II. Origins of timing cancer treatment.
AB  - This paper is a memorial to Mikhail Victorovich Berezkin (MVB) (10 April 1940 -
      16 January 2005), an enthusiastic advocate of chrono-oncology. It illustrates his
      early dose- and circadian time-response curves, limited as yet by a 4-timepoint
      approach, provides a list of his publications, and offers a succinct overview of
      individualized marker rhythm-guided oncotherapy.

PMID- 17228528
TI  - Dr. Robert J. Wright receives the Dr. Jack E. Wells Memorial Dedication to
      Dentistry Award.

PMID- 17228527
TI  - Cancer chronomics III. Chronomics for cancer, aging, melatonin and experimental
      therapeutics researchers.
AB  - This position paper documents the merit of including for basic and clinical
      investigations the mapping of circadian and other rhythms and yet broader
      chronomes, time structures in and around us. Chronobiometry used herein relies on
      inferential statistical methods and on materials documented earlier. The
      circadian amplitude of melatonin is shown to relate both to cancer risk and to
      the presence of overt cancer, when no differences are found in the 24-hour
      average of melatonin. Optimization of treatment by timing, thoroughly documented
      along the circadian scale earlier, could be broadened to include optimization
      along the scale of the week, and eventually beyond. In both cases, reliance on
      marker rhythmometry is advocated. More generally, the limits of knowledge are
      expanded by considering already mapped spectral components and their
      characteristics that can be influenced by the dynamics of heliogeomagnetic
      signals heretofore unassessed.

PMID- 17228529
TI  - How help became available.

PMID- 17228530
TI  - Chemical dependency and dentistry.

PMID- 17228531
TI  - The Tennessee Dental Association Concerned Dental Professionals Committee.

PMID- 17228532
TI  - Genetics and the disease of chemical dependency.

PMID- 17228533
TI  - Nitrous oxide abuse: dentistry's unique addiction.

PMID- 17228534
TI  - Methamphetamine and meth mouth: an overview.

PMID- 17228535
TI  - How chemical dependency affects the dental office family.

PMID- 17228536
TI  - Baldrige interrupted. Premier and North Mississippi both took home the
      prestigious quality award, but their victory celebrations were shortlived.
AB  - Winning an award as prestigious as the Malcolm Baldrige Quality Award is usually
      excellent news. For two recent victors, however, their wins were overshadowed by
      questions over past business practices and possible conflicts of interest, in
      particular at alliance Premier. (At right, a Premier employee conducts client
      training).

PMID- 17228537
TI  - CEOs focus on finances, docs. Execs cite financial challenges as No. 1 problem:
      ACHE.

PMID- 17228538
TI  - Managed-care shake-up. Two major Mich. players leaving insurance business.

PMID- 17228539
TI  - Part D extension. Some get more time to enroll in drug program.

PMID- 17228540
TI  - N.Y.'s turn. Groups formulating universal plans.

PMID- 17228541
TI  - Emergency preparedness. Texas system scores first with inflatable surge hospital.

PMID- 17228542
TI  - Healthcare's sacred cows. Have Berwick and Gingrich become too powerful for the
      common good?

PMID- 17228543
TI  - Consumers are king. From IT projects to quality initiatives to improved
      transparency, in '07 it's all about making the healthcare experience better,
      safer.

PMID- 17228544
TI  - Looking beyond the horizon. Systems buck investment trends, going longer-term
      with 'alternative' portfolios.

PMID- 17228545
TI  - Hitting resistance. Two doc-owned hospitals sell to not-for-profits.

PMID- 17228547
TI  - Tuberculosis: where are we going?

PMID- 17228546
TI  - The future of the acute hospital.

PMID- 17228549
TI  - Self-harm in the general hospital.

PMID- 17228548
TI  - Targeting cancers with tyrosine kinase inhibitors: lessons learned from chronic
      myeloid leukaemia.

PMID- 17228550
TI  - Depression in physical illness.

PMID- 17228551
TI  - Why illness perceptions matter.

PMID- 17228552
TI  - Delirium: an update on diagnosis, treatment and prevention.

PMID- 17228553
TI  - Psychological treatments in liaison psychiatry: the evidence base.

PMID- 17228554
TI  - What can the UK learn from the USA about improving the quality and safety of
      healthcare?
AB  - The US healthcare system provides evidence that spending more on healthcare does
      not result in better care, but also offers many lessons and surprises on how the
      quality and safety of healthcare can be improved. The US Institute of Medicine
      has clearly articulated what needs to be achieved. A series of US agencies,
      including the Joint Commission on Accreditation of Healthcare Organizations, the
      Centers for Medicare and Medicaid Services (CMS), other major players, and the
      Hospital Quality Alliance, routinely collect and report on numerous measures of
      the quality and safety of inpatient and outpatient healthcare. Most attention to
      improving care in the UK has focused on vertically integrated, closed healthcare
      systems, but the US experience provides additional models from the work of
      Quality Improvement Organizations and of numerous voluntary organisations that
      sponsor collaborative improvement.

PMID- 17228555
TI  - Health in an unequal world: social circumstances, biology and disease.

PMID- 17228556
TI  - Understanding hypoxia signalling in cells--a new therapeutic opportunity?
AB  - The possibility that cells possess specific interfaces with molecular oxygen that
      have a prime function in biological control has long interested biologists.
      Specific 'oxygen-sensing' mechanisms have been defined in bacteria and yeast,
      but, until recently, have remained elusive in higher organisms. Studies of
      hypoxia pathways have now, however, revealed the existence of a series of non
      haem Fe(ll) and 2-oxoglutarate-dependent dioxygenases that catalyse oxygen
      regulated hydroxylation of specific amino acids in a key transcription factor
      termed hypoxia-inducible factors (HIFs). These post-translational hydroxylations
      govern both the proteolytic stability and activity of HIF and therefore the
      transcription of many hundreds of human genes whose expression changes in
      accordance with cellular oxygen availability. This paper will review these
      developments and consider the biological and potential therapeutic implications.

PMID- 17228557
TI  - Mother and child care in art.

PMID- 17228558
TI  - Development of a pictorial scale of pain intensity for patients with
      communication impairments: initial validation in a general population.
AB  - This study evaluated a new six-point ordinal scale for measuring pain intensity.
      Seventy-two participants aged between 23 and 87 years rated the intensity of
      'present pain' as well as remembered episodes of 'severe' and 'mild' pain on the
      scale of pain intensity (SPIN), a 10 cm visual analogue scale (VAS) and a 0-10
      numeric scale, in random order. Retesting followed an intervening assessment.
      Participants' comments on the scales were analysed thematically. Spearman's
      correlation between scales all exceeded 0.78 (p<O.O01). Test-retest of the SPIN
      gave percentage agreements (weighted kappa) of present pain 69% (0.83), severe
      pain 94% (0.94) and mild pain 83% (0.85). Most participants preferred using an
      ordinal scale to the continuous VAS. Some found numbers easier to use whereas
      others found the SPIN more helpful. We conclude that the SPIN provides a valid
      measure of pain intensity in patients fully able to communicate their views and
      experiences. Investigation in patients with cognitive or communication
      impairments is now required.

PMID- 17228559
TI  - Is sensible use being made of an inpatient Holter monitoring and transthoracic
      echocardiogram service within acute medicine?
AB  - Transthoracic echocardiograms (TTE) and 24-hour Holter recordings are commonly
      requested investigations for patients presenting with symptoms thought to be due
      to underlying cardiac pathology. The objective of this study was to audit the use
      of inpatient TTE and Holter monitors in acute medical patients under the care of
      physicians other than cardiologists within a tertiary cardiology referral centre.
      This was accomplished by a retrospective analysis of 4,623 TTE and 3,145 Holters
      reported by cardiologists between 8 October 1999 and 3 November 2005. The age
      range for Holter monitoring was 16-104 years, mean 70 (SD 18) years. The age
      range for TTE was 16-101 years, mean 68 (SD 17) years. Of the Holters performed,
      69.1% were within normal limits. Atrial fibrillation/flutter was the commonest
      arrhythmia, found in 787 patients (25.0%). A total of 99 patients were referred
      to a cardiologist; 47 of these patients were permanently paced. Of the TTE
      requests to assess left ventricular function, 44.8% were normal. A cardiac source
      of embolism was found in 1.8% of requests to assess for this. TTE requests for
      infective endocarditis confirmed the diagnosis in 4.1% of patients. Holter
      investigation and TTE were commonly requested investigations; a large proportion
      of both, however, were within normal limits. This suggests that more
      consideration is required before making the request for Holter investigation and
      TTE, as more appropriate investigations may be available.

PMID- 17228560
TI  - Constrictive pericarditis: lessons from the past five years' experience in the
      South West Cardiothoracic Centre.
AB  - There are still patients who develop constrictive pericarditis. The aetiology has
      changed from times when it usually resulted from tuberculosis or purulent
      infection. The symptoms and signs may be misinterpreted and lead to the wrong
      diagnosis of congestive cardiac failure, lung disease, or liver disease. Patients
      with constrictive pericarditis present to specialists in different disciplines.
      We describe our experience, over five years, in one tertiary referral centre. We
      highlight the presentation, aetiology, investigation, and treatment and hope to
      remind all physicians of an uncommon but treatable condition.

PMID- 17228561
TI  - Novel strategies for protection and repair of the central nervous system.
AB  - Clinical possibilities in many neurological conditions are limited by our current
      inability to correct structural damage to the nervous system, and treatments to
      prevent damage are also limited. Current research has produced promising
      treatments that promote neuroprotection, plasticity, axon regeneration,
      remyelination and cell replacement. As these treatments go through clinical
      trials and enter the clinic, the treatment of several neurological conditions
      will change greatly.

PMID- 17228563
TI  - General medicine for the physician.

PMID- 17228562
TI  - Medicine at high altitude.
AB  - Medicine at high altitude provides important insights into the acute and chronic
      effects of hypoxia. Acute mountain sickness (AMS) is a common syndrome occurring
      after acute ascent to over 2,500 m and is caused by increased capillary
      permeability. A number of factors have been identified that increase the risk of
      AMS, in particular exercise. Avoiding rapid ascent, undue exercise and the use of
      acetazolamide are useful preventative measures but severe symptoms may require
      oxygen, dexamethasone and descent. Acute mountain sickness is usually self
      limiting but may progress into the serious syndromes of pulmonary and cerebral
      oedema. Acclimatisation and adaptation are important for workers and residents at
      high altitude and the improvement seen in maximum exercise has been incorporated
      into some training schedules for endurance athletes. Chronic and subacute high
      altitude diseases largely result from polycythemia and pulmonary hypertension.

PMID- 17228564
TI  - Cardiac arrests at the Cenotaph.
AB  - This report describes the case histories of three veterans who suffered cardiac
      arrests at the 2005 Cenotaph Remembrance Parade. All three were successfully
      resuscitated and admitted to the St Thomas' Hospital Coronary Care Unit. They had
      internal cardioverter defibrillators (ICDs) inserted and remain well. All three
      plan to attend Remembrance ceremonies this year. We review the evidence between
      emotional stress and arrhythmias and the updated National Institute for Health
      and Clinical Excellence (NICE) guidelines for ICDs.

PMID- 17228565
TI  - Current clinical uses of intravenous immunoglobulin.

PMID- 17228566
TI  - Skin cancer: prevalence, prevention and treatment.

PMID- 17228567
TI  - Systematic review of systematic reviews of acupuncture published 1996-2005.

PMID- 17228568
TI  - Who's for five nine-hour shifts a week?

PMID- 17228570
TI  - Creationism or evolution: is there a valid distinction?

PMID- 17228569
TI  - Communicating information on cardiopulmonary resuscitation to hospitalised
      patients.

PMID- 17228571
TI  - Equine conformation: clues to performance and soundness?

PMID- 17228572
TI  - Prevalence, heritability and significance of musculoskeletal conformational
      traits in Thoroughbred yearlings.
AB  - REASONS FOR PERFORMING STUDY: The assessment of belief that equine conformation
      is associated with performance and durability is a fundamental concept of
      horsemanship. Surprisingly, there is almost no quantitative evidence to support
      these beliefs. OBJECTIVES: To assess the prevalence and heritability of
      conformational traits in Thoroughbred yearlings, and investigate their
      significance for subsequent turf flat-racing performance and durability. METHODS:
      Nine selected conformational traits were assessed in a consistent, qualitative
      manner by a single veterinary observer and entered into a database together with
      details of pedigree and racing records. RESULTS: Conformational data were
      collected from 3916 Thoroughbred yearlings sold at public auction during the 7
      year period 1993-1999. Most of the horses (72%) raced in the UK in turf flat
      races; just 7% of the yearlings failed to race. Prevalence of conformational
      defects for the UK horses was reported, with turned out feet the most commonly
      recorded defect (30% of all horses). There was a tendency towards a greater
      proportion of horses with defects in the group of unraced horses compared with
      horses that raced, but this was not statistically significant. There were some
      significant associations between racing performance and conformational defects
      but these were found to be almost completely explained by an effect of sire. All
      of the conformational traits showed considerable evidence of genetic influence,
      with heritability indices ranging 0.16-1.00. CONCLUSIONS AND POTENTIAL RELEVANCE:
      Overall, there were only weak associations between performance and conformation
      that could not be accounted for by the very strong relationship between pedigree
      and conformation. Further study of potential association between highly heritable
      conformation traits and racing durability and racing performance should be
      undertaken utilising validated, quantitative methods and technology.

PMID- 17228573
TI  - Carpal and fetlock conformation of the juvenile Thoroughbred from birth to
      yearling auction age.
AB  - REASONS FOR PERFORMING STUDY: There is little information available about
      conformational changes in the forelimbs of growing foals. OBJECTIVES: To describe
      the conformation of the carpus and fetlock of Thoroughbred foals from birth to
      yearling sale age. METHODS: Subjective assessments of the fetlock and carpal
      conformation of 119 Thoroughbred foals were made within the first month of life
      and then at 30 day intervals until at least age 120 days. At least 70 subjects
      were examined further at 60 day intervals until September of their second year.
      Conformation grades are reported for 5 age groups: first 7 days and at a mean of
      46, 176, 362 and 525 days. The conformation of all available sires and dams of
      subjects was also graded. RESULTS: All subjects demonstrated carpal deviations,
      such as valgus, outward rotation and offset, and approximately 30% had fetlock
      deviations. Heavier birth weights were associated with carpal offset and fetlock
      inward conformation at most ages, and heavier yearlings were more likely to be
      carpal valgus. The carpal conformation of the sire (offset and outward rotation)
      was associated with similar yearling carpal conformation. During the study
      period, the carpal conformation of Thoroughbred foals became less valgus and more
      offset. Fetlock conformation became more inwardly deviated during the first 6
      months of the study. CONCLUSIONS: Carpal and fetlock conformation change greatly
      in Thoroughbred foals up to age 18 months. The phenotype of the sire can be
      associated with yearling carpal conformation and bodyweight, particularly at
      birth and as yearlings, is associated with yearling fetlock and carpal
      conformation. POTENTIAL RELEVANCE: New factors associated with forelimb
      conformational deviations have been identified that may help breeders better to
      manage young racing stock.

PMID- 17228574
TI  - Reliability of conformational measurements in the horse using a three-dimensional
      motion analysis system.
AB  - REASONS FOR PERFORMING STUDY: The importance of a reliable method for
      conformation studies is generally acknowledged, but there are only limited data
      on the accuracy and precision of current assessment methods. OBJECTIVES: To
      assess (1) the accuracy and repeatability of marker placement, (2) influence of
      stance of the horse on conformational parameters, (3) practicality of a
      computerised motion analysis system and (4) to compare the computerised motion
      analysis system to photographic systems of assessment. METHODS: Twenty-eight
      reflective markers placed over anatomical landmarks were located in 3D using a
      computerised motion analysis system and their coordinates used to calculate
      segment lengths and joint angles. Four experiments, involving a cadaver study, a
      series of repeated measures on a single Thoroughbred and repeat measurements on
      108 racehorses were performed. RESULTS: Identification of anatomical landmarks
      was found to introduce the biggest variation in the measurements for proximal
      conformation parameters with the interoperator being larger than intraoperator
      variation. Length measurements were least influenced by stance, with distal
      interphalangeal and metacarpo/metatarsophalangeal joint angles being the most
      variable. In some measurements, the variation between stances within a horse
      proved to be almost as large as between horses, rendering these parameters less
      useful as predictors of performance or orthopaedic health. CONCLUSIONS: A
      computerised motion analysis system allows 3D assessment of conformation with
      high accuracy and precision. It eliminates 3 major sources of error associated
      with photography-based methods and increases accuracy of conformational
      assessment by allowing repeat measurements in a relatively short period.
      POTENTIAL RELEVANCE: Studies on conformation should be viewed in the light of the
      limitations of the measurement technique used. The presented method maximises
      accuracy and precision and is a valuable basis for future studies investigating
      the effect of conformation on performance or orthopaedic health.

PMID- 17228575
TI  - Variation in conformation in a cohort of National Hunt racehorses.
AB  - REASONS FOR PERFORMING THE STUDY: Assessment of conformation is commonly used in
      the selection of horses for performance purposes. Little information is available
      on the normal range of conformational traits within the Thoroughbred population.
      OBJECTIVES: To describe variations in conformation in a cohort of racing
      Thoroughbreds in order to provide a set of baseline standards within which
      conformational traits can be considered normal. MATERIALS AND METHODS: Ninety
      eight conformational parameters were measured in a cohort of 108 National Hunt
      racehorses using a digital motion analysis system. The measurements consisted of
      segment lengths, joint angles in 2D and 3D, inclinations, deviations and
      circumference measurements. The differences between left and right sides were
      determined to obtain a measure of asymmetry. Conformational parameters were
      related to each horse's country of origin, preferred race distance and race type.
      RESULTS: The majority of parameters followed a normal distribution with the
      biggest relative variation in hoof related measurements and in stifle and coxal
      angle. All circumference measurements and the majority of the length measurements
      were significantly correlated with the height of the horse at the withers. No
      underlying pattern of combinations of conformational parameters was identified.
      Twenty-five per cent of the parameters showed a significant difference between
      left and right-sided measurements. A significant difference in girth and
      intermandibular width was observed between Irish and French horses. CONCLUSIONS:
      Thoroughbreds differ from other breeds, not only with regard to segment lengths
      but also with regard to joint angles and deviations. Variation in conformational
      parameters was relatively small and no distinct pattern of combinations of
      conformational traits identified. CLINICAL RELEVANCE: The variation in
      conformational measurements in Thoroughbred racehorses establishes a set of
      baseline measurements of conformational range against which individual horses can
      be assessed.

PMID- 17228576
TI  - The effect of conformation on orthopaedic health and performance in a cohort of
      National Hunt racehorses: preliminary results.
AB  - REASONS FOR PERFORMING STUDY: There is a lack of scientific data and studies on
      the effect of conformation on performance or on orthopaedic health. OBJECTIVES:
      To investigate the relationship between conformation, injury and performance in
      racehorses used for racing over fences. METHODS: Over 2 years, 108 National Hunt
      racehorses were followed and their medical and performance data recorded.
      Conformation was measured in 3D with a computerised motion analysis system.
      Linear multiple regression models were used to evaluate the effect of
      conformation on measures of race performance and stepwise forward logistic
      regression models to assess the effect on risk of injury. RESULTS: An increase in
      intermandibular width, flexor angle of the shoulder joint and coxal angle (the
      angle between the ilium and ischium) was demonstrated to have a positive effect
      on performance. Performance decreased with increasing girth, length of the hind
      digit and valgus conformation of the metacarpophalangeal joint. The risk of
      suffering from superficial digital flexor tendon injury increased with increasing
      metacarpophalangeal joint angle and with carpus valgus conformation. The risk of
      pelvic fracture increased with valgus conformation of the tarsus and decreased
      with an increasing coxal angle. CONCLUSION: Valgus deformation was demonstrated
      to be detrimental to performance or increased risk of injury, perhaps resulting
      in higher loads on musculoskeletal structures. The coxal angle was the only
      parameter to have an effect on both risk of injury and performance. An alignment
      of the muscles with the axis of the pelvis may be beneficial for force
      transmission and decrease the bending moment of the muscles on the bones. The
      statistical power of this study is limited, however it provides preliminary data
      necessary for the planning of a larger scale study on the effect of conformation
      on performance and risk of injury. CLINICAL RELEVANCE: Studies of the effects of
      conformation on performance and risk of injury may aid in identifying individuals
      likely to perform well on the racecourse and avoid risks of injury.

PMID- 17228577
TI  - Effect of standing tarsal angle on joint kinematics and kinetics.
AB  - REASONS FOR PERFORMING STUDY: The tarsal joint is a frequent site of lameness,
      but little objective information is available regarding the effects of tarsal
      conformation on joint movements or forces. OBJECTIVE: To compare tarsal
      kinematics and kinetics in horses with large, intermediate and small tarsal
      angles. METHODS: Sagittal plane standing angle of the right tarsal joint was
      measured in 16 horses as they stood squarely with the hind hooves vertically
      beneath the hip joint. Tarsal angles were classified as small (< 155.5 degrees),
      intermediate (155.5-165.5 degrees) or large (> 165.5 degrees). Reflective
      markers, attached over the centres of joint rotation, were tracked during stance
      as the horses trotted across a force plate at a standardised speed. Joint angles
      and ground reaction forces were combined with morphometric data to calculate net
      joint moments and net joint powers across the tarsus using inverse dynamics.
      RESULTS: In all horses, the tarsus flexed during the impact phase and extended in
      late stance. Tarsal angles were stratified according to standing tarsal angle
      throughout stance. Horses with large standing angles showed less flexion and less
      energy absorption at the tarsus during the impact phase than those with
      intermediate or small angles and generated less vertical impulse than horses with
      small standing angles. Net extensor moment at the tarsus during stance was lower
      for horses with large standing angles. CONCLUSIONS: In horses with large tarsal
      angles, less concussion was absorbed during the impact phase, which may be a
      factor in the development of degenerative joint disease; and the smaller vertical
      impulse and extensor moment later in stance may limit propulsive ability.
      However, the smaller net joint moment may reduce the risk of plantar ligament
      desmitis. CLINICAL SIGNIFICANCE: The effects of conformation on kinematics and
      kinetics of the tarsal joint may influence both performance and soundness.

PMID- 17228578
TI  - Hoof ground interaction: when biomechanical stimuli challenge the tissues of the
      distal limb.

PMID- 17228579
TI  - Hoof growth and wear of semi-feral ponies during an annual summer 'self-trimming'
      period.
AB  - REASONS FOR PERFORMING STUDY: Despite growing interest in application natural
      models of hoof-maintenance in domestic horses, little data is available to
      describe natural conformation and proposed mechanisms of self-maintenance.
      OBJECTIVES: Quantitatively describe hoof growth and wear during a period of 'self
      trimming' within a herd of semi-feral ponies. METHODS: Hoof length, growth and
      wear were measured for a sample of 40 animals during a period of 'self-trimming'
      from June through September, 2005. RESULTS: For front hooves, mean toe lengths in
      July, August and September were significantly less than in June. For the hind,
      mean toe length in August was significantly less than in June, July and
      September. Increased rate of wear, as opposed to decreased growth rate, was the
      major contributor to overall shorter hoof lengths. Cumulative wear expressed as a
      percentage of the June baseline toe length ranged from 21-57% (mean 38%) for the
      front and 12-46% (mean 32%) for the hind. CONCLUSIONS: Significant cracking,
      tearing and increased wear, known as 'self-trimming' is a measurable herd-wise
      phenomenon in horses maintained under natural social and environmental
      conditions. POTENTIAL RELEVANCE: Although just one example herd, these data
      provide quantitative support of anecdotal reports of 'self-trimming' as a
      mechanism contributing to natural self-maintenance of the equine hoof.

PMID- 17228580
TI  - Uneven feet in a foal may develop as a consequence of lateral grazing behaviour
      induced by conformational traits.
AB  - REASONS FOR PERFORMING STUDY: Conformational traits are important in breeding,
      since they may be indicative for performance ability and susceptibility to
      injuries. OBJECTIVES: To study whether certain desired conformational traits of
      foals are related to lateralised behaviour while foraging and to the development
      of uneven feet. METHODS: Twenty-four Warmblood foals, born and raised at the same
      location, were studied for a year. Foraging behaviour was observed by means of
      weekly 10 min scan-sampling for 8 h. A preference test (PT) was developed to
      serve as a standardised tool to determine laterality. The foals were evaluated at
      age 3, 15, 27 and 55 weeks. The PT and distal limb conformation were used to
      study the relation between overall body conformation, laterality and the
      development of uneven feet. Pressure measurements were used to determine the
      loading patterns under the feet. RESULTS: About 50% of the foals developed a
      significant preference to protract the same limb systematically while grazing,
      which resulted in uneven feet and subsequently uneven loading patterns. Foals
      with relatively long limbs and small heads were predisposed to develop laterality
      and, consequently unevenness. CONCLUSIONS: Conformational traits may stimulate
      the development of laterality and therefore indirectly cause uneven feet.

PMID- 17228581
TI  - Developmental aspects of distal limb conformation in the horse: the potential
      consequences of uneven feet in foals.
AB  - REASONS FOR PERFORMING STUDY: Distal limb conformation is generally accepted to
      be an important item with respect to performance and soundness in mature horses,
      but little is known about the developmental aspects. OBJECTIVES: To gain insight
      into the development of distal limb conformation and to assess the possible
      consequences of uneven feet in foals. METHODS: Conformation of the distal front
      limbs of 23 Warmblood foals was scored visually and measured using radiographs,
      at ages 27 and 55 weeks. At the same ages, pressure measurements were made under
      both front feet. RESULTS: At both ages the hoof-pastern axis was broken-backwards
      on radiographs, but only occasionally recognised as such, when scored by eye.
      Over time, the hoof angle decreased, while both the angles of the dorsal and
      solar surfaces of the distal phalanx (P3) increased and the parallelism between
      hoof wall and P3 improved. The foals with uneven feet at age 27 weeks showed a
      significant difference in distal limb loading that persisted until age 55 weeks.
      CONCLUSIONS: The alignment of the distal limb in the sagittal plane increased in
      a 6 month period. Visual assessment was not sensitive enough to appreciate this.
      The growth processes in the distal limb could not compensate for existing
      unevenness and ensuing asymmetrical limb loading. POTENTIAL RELEVANCE: Foals have
      a different conformation of the distal limb from mature horses, which should be
      taken into account when interpreting radiographs. Unevenness of the feet resulted
      in asymmetrical loading of the proximal and distal interphalangeal joint, which
      might lead to increased susceptibility to overload injuries and decreased
      performance at mature age.

PMID- 17228582
TI  - Time domain characteristics of hoof-ground interaction at the onset of stance
      phase.
AB  - REASONS FOR PERFORMING STUDY: Little is known about the interaction of the hoof
      with the ground at the onset of stance phase although is it widely believed that
      high power collisions are involved in the aetiopathology of several conditions
      causing lameness. OBJECTIVES: To answer 3 questions regarding the fundamental
      nature of hoof-ground collision: (1) is the collision process deterministic for
      ground surfaces that present a consistent mechanical interface (2) do collision
      forces act on the hoof in a small or large range of directions and (3) Is the
      hoof decelerated to near-zero velocity by the initial deceleration peak following
      ground contact? METHODS: Hoof acceleration during the onset of stance phase was
      recorded using biaxial accelerometry for horses trotting on a tarmac surface and
      on a sand surface. Characteristics of the collision process were identified both
      from vector plots and time series representations of hoof acceleration, velocity
      and displacement. RESULTS: The response of the hoof to collision with smooth
      tarmac was predominantly deterministic and consistent with the response of a
      spring-damper system following shock excitation. The response to collision with
      sand was predominantly random. The deceleration peak following ground contact did
      not decelerate the hoof to near-zero velocity on tarmac but appeared to on sand.
      On both surfaces, collision forces acted on the hoof in a wide range of
      directions. CONCLUSIONS: The study suggests the presence of stiff, viscoelastic
      structures within the foot that may act as shock absorbers isolating the limb
      from large collision forces. POTENTIAL RELEVANCE: The study indicates objectives
      for future in vivo and in vitro research into the shock absorbing mechanism
      within the equine foot; and the effects of shoe type and track surface properties
      on the collision forces experienced during locomotion. Studies of this nature
      should help to establish a link between musculoskeletal injury, hoof function and
      hoof-ground interaction if, indeed, one exists.

PMID- 17228583
TI  - The horse-racetrack interface: a preliminary study on the effect of shoeing on
      impact trauma using a novel wireless data acquisition system.
AB  - REASONS FOR PERFORMING STUDY: There is a need to determine accelerations acting
      on the equine hoof under field conditions in order to better assess the risks for
      orthopaedic health associated with shoeing practices and/or surface conditions.
      OBJECTIVES: To measure the acceleration profiles generated in Thoroughbred
      racehorses exercising at high speeds over dirt racetracks and specifically to
      evaluate the effect of a toe grab shoe compared to a flat racing plate, using a
      newly developed wireless data acquisition system (WDAS). METHODS: Four
      Thoroughbred racehorses in training and racing were used. Based on previous
      trials, each horse served as its own control for speed trials, with shoe type as
      variable. Horses were evaluated at speeds ranging from 12.0-17.3 m/sec. Impact
      accelerations, acceleration on break over and take-off, and temporal stride
      parameters were calculated. Impact injury scores were also determined, using peak
      accelerations and the time over which they occurred. RESULTS: Recorded
      accelerations for the resultant vector (all horses all speeds) calculated from
      triaxial accelerometers ranged 96.3-251.1 g, depending on the phase of the impact
      event. An association was observed between shoe type and change in acceleration
      in individual horses, with 2 horses having increased g on initial impact with toe
      grab shoes in place. In the final impact phase, one horse had an increase of 110
      g while wearing toe grab shoes. Increased accelerations were also observed on
      break over in 2 horses while wearing toe grab shoes. CONCLUSIONS: Shoe type may
      change impact accelerations significantly in an individual horse and could
      represent increased risk for injury. Further work is needed to determine if
      trends exist across a population. POTENTIAL RELEVANCE: The WDAS could be used for
      performance evaluation in individual horses to evaluate any component of the
      horse-performance surface interface, with the goal of minimising risk and
      optimising performance.

PMID- 17228584
TI  - A novel wireless data acquisition system for the measurement of hoof
      accelerations in the exercising horse.
AB  - REASONS FOR PERFORMING STUDY: A device is needed to safely and wirelessly
      evaluate accelerations experienced by the horse hoof under a variety of surface
      conditions with the horse exercising at training or racing speeds. OBJECTIVES: To
      develop a miniaturised wireless data acquisition system (WDAS) which reliably
      records hoof accelerations and the times over which they occur in a minimally
      invasive manner in the exercising Thoroughbred. METHODS: The following criteria
      were set for device development: production of a lightweight and minimally
      invasive system, which provides an adequate acceleration range, appropriate
      frequency response to capture high speed events, and compatibility with a low
      power wireless telemetry system. Following device development, the WDAS was
      calibrated, and tested in 6 Thoroughbred horses over a variety of surfaces.
      RESULTS: Collection of acceleration in seven trials using 6 horses over a variety
      of surfaces resulted in repeatable acceleration data with respect to the overall
      characteristic shape of the impact profile. Impact accelerations varied with
      surface, ranging 34.8-191.7 g. Accelerations on take off were in a similar range,
      although higher in some trials. Peak impact accelerations tended to larger over
      the grass paddock surface, than either the indoor arena or the dirt track. During
      dirt track trials, accelerations on take-off were often comparably larger than
      those observed on impact within the same footfall. CONCLUSIONS: This study
      reports the development of a wireless system that successfully measures hoof
      acceleration in a minimally invasive manner over a variety of surface and
      exercise conditions. POTENTIAL RELEVANCE: The WDAS will be used in further
      studies to evaluate various components of the horse-racetrack interface, in an
      attempt to identify risk factors for musculoskeletal injury in the Thoroughbred
      racehorse.

PMID- 17228586
TI  - The corticosteroid laminitis story: 1. Duty of care.

PMID- 17228585
TI  - The use of MP3 recorders to log data from equine hoof mounted accelerometers.
AB  - REASONS FOR PERFORMING STUDY: MP3 recorders are readily available, small,
      lightweight and low cost, providing the potential for logging analogue hoof
      mounted accelerometer signals for the characterisation of equine locomotion.
      These, however, require testing in practice. OBJECTIVES: To test whether 1)
      multiple MP3 recorders can maintain synchronisation, giving the ability to
      synchronise independent recorders for the logging of multiple limbs
      simultaneously; and 2) features of a foot mounted accelerometer signal
      attributable to foot-on and foot-off can be accurately identified from horse foot
      mounted accelerometers logged directly into an MP3 recorder. METHODS: Three
      experiments were performed: 1) Maintenance of synchronisation was assessed by
      counting the number of samples recorded by each of 4 MP3 recorders while mounted
      on a trotting horse and over 2 consecutive 30 min periods in 8 recorders on a
      bench. 2) Foot-on and foot-off times obtained from manual transcription of MP3
      logged data and directly logged accelerometer signal were compared. 3)
      MP3/accelerometer acquisition units were used to log accelerometer signals from
      racehorses during extended training sessions. RESULTS: Mean absolute error of
      synchronisation between MP3 recorders was 10 samples per million (compared to
      mean number of samples, range 1-32 samples per million). Error accumulation
      showed a linear correlation with time. Features attributable to foot on and foot
      off were equally identifiable from the MP3 recorded signal over a range of equine
      gaits. CONCLUSIONS: Multiple MP3 recorders can be synchronised and used as a
      relatively cheap, robust, reliable and accurate logging system when combined with
      an accelerometer and external battery for the specific application of the
      measurement of stride timing variables across the range of equine gaits during
      field locomotion. POTENTIAL RELEVANCE: Footfall timings can be used to identify
      intervals between the fore and hind contacts, the identification of diagonal
      advanced placement and to calculate stride timing variables (stance time,
      protraction time and stride time). These parameters are invaluable for the
      characterisation and assessment of equine locomotion.

PMID- 17228587
TI  - The corticosteroid laminitis story: 2. Science of if, when and how.

PMID- 17228588
TI  - The corticosteroid laminitis story: 3. The clinician's viewpoint.

PMID- 17228589
TI  - The role of biomechanics in the study of conformation and its relationship to
      orthopaedic health.

PMID- 17228590
TI  - Endoscopic assessment and treatment of lesions of the deep digital flexor tendon
      in the navicular bursae of 20 lame horses.
AB  - REASONS FOR PERFORMING STUDY: Clinical lesions of the deep digital flexor tendon
      and navicular bone are being reported with increasing frequency. However, the
      role of direct visualisation by navicular bursoscopy in the diagnosis and
      management of such injuries has not been explored. HYPOTHESIS: Navicular
      bursoscopy: 1) corroborates information obtained from other, noninvasive imaging
      modalities; 2) allows direct visualisation of lesions unidentified by other
      diagnostic modalities; 3) provides further information on morphology of lesions;
      and 4) permits minimally invasive surgical access to lesions. METHODS: The case
      records of all horses that underwent diagnostic navicular bursoscopy for the
      investigation of lameness admitted to 2 referral clinics (the Royal Veterinary
      College and Reynolds House Referrals) were evaluated retrospectively. Follow-up
      information was obtained by telephone questionnaire. RESULTS: Twenty-three bursae
      were examined endoscopically in 20 horses. Tears of the deep digital flexor
      tendon were seen in all horses (22 bursae). In 8 bursae, cartilage lesions were
      also present and in one bursa this was the only abnormal finding. Computed
      tomography and low field magnetic resonance imaging predicted tendon lesions in
      most cases, but failed to identify cartilage damage. Greater than 6 month follow
      up information was available for 15 animals of which 11 were sound and 9 had
      returned to preoperative levels of performance. CONCLUSION: Lameness localised to
      the foot may result from tears of the deep digital flexor tendon and/or navicular
      fibrocartilage loss. Navicular bursoscopy allows comprehensive evaluation of
      these changes and also permits appropriate lesion management. POTENTIAL
      RELEVANCE: The diagnostic information obtained from and therapeutic options
      offered by bursoscopy justify its use in horses with clinical findings localising
      lameness to the navicular bursa.

PMID- 17228591
TI  - Morphological alterations in oxidative muscles and mitochondrial structure
      associated with equine atypical myopathy.
AB  - REASONS FOR PERFORMING STUDY: There is a lack of well documented studies about
      muscular lesions in equine atypical myopathy (EAM). OBJECTIVES: To characterise
      morphopathological changes of striated muscles and myocardium, to progress
      understanding of this disease. METHODS: Thirty-two horses age 0.5-7 years kept on
      pasture were referred for a sudden ataxia/myoglobinuria syndrome. Clinical
      examination (stiffness, muscle pain, muscle fasciculations, abnormal gait,
      recumbency, myoglobinuria, tachycardia, sweating) and plasma CPK, LDH and AST
      levels were consistent with extensive myonecrosis and, together with anamnestic
      data, with so-called 'equine atypical myopathy' (EAM), a disease of unknown
      aetiology reported since 1939. Macroscopic and microscopic (histology,
      histoenzymology, ultrastructure) lesions were evaluated. RESULTS: Necropsic
      examination revealed large areas of muscle necrosis, the extent and severity of
      which varied between cases and muscles, but which were clearly more constant and
      severe in respiratory and postural muscles and in the myocardium. Histology
      highlighted a multifocal and monophasic process compatible with Zenker
      degeneration/necrosis that mostly and segmentally affected type 1 fibres.
      Histochemical evaluation revealed a weak and disorganised pattern of NADH
      tetrazolium reductase staining, the absence of calcium salts precipitates and a
      dramatic accumulation of lipid droplets. Ultrastructural examination often
      revealed fibres of which the sole modifications were altered mitochondria and
      sarcoplasmic lipidosis. CONCLUSIONS: Taken together, the data suggest that a
      primary alteration of mitochondria should be considered, although secondary
      mitochondrial abnormalities have yet to be ruled out. POTENTIAL RELEVANCE: The
      morphological features gathered here reveal that EAM shares most of the
      characteristics of toxic myopathies.

PMID- 17228592
TI  - The effect of uterine torsion on mare and foal survival: a retrospective study,
      1985--2005.
AB  - REASONS FOR PERFORMING STUDY: Anecdotal speculation suggests that prognosis for
      survival of mares and foals following correction of uterine torsion has improved
      over the past 30 years. OBJECTIVES: To determine statistically the outcome of
      uterine torsion according to duration of clinical signs, stage of gestation,
      parity, physical examination findings, method of correction, prognosis for
      survival and reproductive health of the mare, and prospects for the foal within
      the neonatal period. METHODS: This retrospective study combined cases from 4
      equine referral hospitals. RESULTS: The stage of gestation at which uterine
      torsion occurred was a risk factor for survival of mare and foal. Overall mare
      survival was 53/63 (84%); when uterine torsion occurred at < 320 days gestation,
      36/37 (97%) of mares survived compared to 17/26 (65%) survival rate when uterine
      torsion occurred at > or = 320 days gestation. Overall foal survival was 54%
      (29/54). When uterine torsion occurred at < 320 days gestation, 21/29 (72%) foals
      survived compared to 8/25 (32%) when uterine torsion occurred at > or = 320 days
      gestation. Thirty mares were discharged from the hospital carrying a viable fetus
      following uterine torsion correction and 25/30 (83%) of these mares delivered
      live foals that survived beyond the neonatal period. CONCLUSIONS: Prognosis for
      survival for mares and foals following uterine torsion is good and improves if
      torsion occurs < 320 days compared to > or = 320 days gestation. CLINICAL
      RELEVANCE: Gestational timing of uterine torsion should be considered when
      advising clients about the prognosis for survival of the mare and foal. The
      prognosis for a mare delivering a live foal is good if the mare is discharged
      from the hospital following uterine torsion correction with a viable fetus.

PMID- 17228593
TI  - Retrospective study of dystocia in mares at a referral hospital.
AB  - REASONS FOR PERFORMING STUDY: The period between the onset of dystocia and its
      resolution has an important bearing on fetal outcome. There are few published
      data on which to base decisions regarding optimum management of cases in
      practice. OBJECTIVES: To evaluate and compare the effects of a coordinated
      dystocia management protocol (CDMP) with that of a previous protocol of random
      management on time to resolution and outcome in both an emergency dystocia
      referral population of mares (referred emergency cases: EM) and in a population
      of mares residing in hospital due to high risk pregnancy (HRP) concerns that then
      experience dystocia at parturition. METHODS: Retrospective study performed at a
      university hospital referral centre of cases presenting from 1991-2004 divided
      into Group 1 (pre-CDMP) and Group 2 (CDMP). RESULTS: Medical records of 71 cases
      with dystocia were retrieved and data recorded. For referred emergency cases
      (EM), time from hospital presentation to resolution decreased significantly by 32
      min (P = 0.03) after institution of CDMP. Survival rate of mares at discharge was
      86%. Survival of EM foals was low, with 10% in Group 1 and 13% in Group 2,
      surviving to discharge. For EM foals delivered alive, survival to discharge was
      30% and 43% in Groups 1 and 2, respectively. Median Stage II was significantly (P
      < 0.001) different at 71 and 282 min for EM foals delivered alive vs. those not
      alive at delivery, respectively. Median duration of Stage II was also
      significantly (P < 0.001) different between EM foals surviving and not surviving
      to discharge, at 44 and 249 min, respectively. Survival of HRP dystocia foals to
      discharge was 79%. CONCLUSIONS: Although CDMP reduced the time from presentation
      at the hospital to resolution significantly for EM, total duration of Stage II
      for EM was unchanged, as was foal outcome. POTENTIAL RELEVANCE: Very early
      referral of mares with dystocia to referral centres with dystocia management
      protocols may improve fetal outcome as increased duration of Stage II in the
      horse affects fetal outcome negatively.

PMID- 17228594
TI  - Lamellar pro-inflammatory cytokine expression patterns in laminitis at the
      developmental stage and at the onset of lameness: innate vs. adaptive immune
      response.
AB  - REASONS FOR PERFORMING STUDY: Recent research has indicated that inflammation
      plays a role in the early stages of laminitis and that, similar to organ failure
      in human sepsis, early inflammatory mechanisms may lead to downstream events
      resulting in lamellar failure. Characterisation of the type of immune response
      (i.e. innate vs. adaptive) is essential in order to develop therapeutic
      strategies to counteract these deleterious events. OBJECTIVES: To quantitate gene
      expression of pro-inflammatory cytokines known to be important in the innate and
      adaptive immune response during the early stages of laminitis, using both the
      black walnut extract (BWE) and oligofructose (OF) models of laminitis. METHODS:
      Real-time qPCR was used to assess lamellar mRNA expression of interleukins-1beta,
      2, 4, 6, 8, 10, 12 and 18, and tumour necrosis factor alpha and interferon gamma
      at the developmental stage and at the onset of lameness. RESULTS: Significantly
      increased lamellar mRNA expression of cytokines important in the innate immune
      response were present at the developmental stage of the BWE model, and at the
      onset of acute lameness in both the BWE model and OF model. Of the cytokines
      characteristic of the Th1 and Th2 arms of the adaptive immune response, a mixed
      response was noted at the onset of acute lameness in the BWE model, whereas the
      response was skewed towards a Th1 response at the onset of lameness in the OF
      model. CONCLUSIONS: Lamellar inflammation is characterised by strong innate
      immune response in the developmental stages of laminitis; and a mixture of innate
      and adaptive immune responses at the onset of lameness. POTENTIAL RELEVANCE:
      These results indicate that anti-inflammatory treatment of early stage laminitis
      (and the horse at risk of laminitis) should include not only therapeutic drugs
      that address prostanoid activity, but should also address the marked increases in
      lamellar cytokine expression.

PMID- 17228595
TI  - Laminar xanthine oxidase, superoxide dismutase and catalase activities in the
      prodromal stage of black-walnut induced equine laminitis.
AB  - REASONS FOR STUDY: Xanthine oxidase (XO)-dependent production of superoxide anion
      and hydrogen peroxide, a characteristic of ischaemia-reperfusion injury, may
      contribute to the development of equine laminitis. OBJECTIVE: To determine the
      levels of XO and antioxidant enzymes (catalase, superoxide dismutase [SOD]) in
      the digital laminae of normal horses (CON) and horses in the developmental stage
      of laminitis using the black walnut extract (BWE) model. METHODS: Healthy horses
      (n = 12) were administered BWE (BWE group, n = 6), or water (CON group, n = 6)
      through a nasogastric tube. At the onset of leucopenia in the BWE-treated
      animals, all horses were anaesthetised, digital laminae and other samples
      collected rapidly and flash frozen, and the animals subjected to euthanasia.
      Extracts of the frozen tissues were assayed for the 2 conformational forms of
      xanthine: oxygen oxidoreductase (XOR), namely, xanthine dehydrogenase (XDH) and
      xanthine oxidase (XO), as well as the antioxidant enzymes, SOD and catalase.
      RESULTS: Extracts of liver, lungs and skin, but not digital laminae, from either
      CON or BWE-treated horses had endogenous SOD, whereas all had endogenous XO and
      catalase. The levels of XDH, XO and catalase were similar in extracts of laminae
      from CON and BWE-treated horses as was the ratio of XDH to XO in extracts.
      CONCLUSIONS AND POTENTIAL RELEVANCE: The absence of increased XO activity suggest
      against the involvement of this reactive oxygen intermediate-generating system in
      the development of laminar pathology in BWE-treated horses. Conversely, the
      absence of SOD from extracts of equine digital laminae, but not other tissues,
      suggests that the equine digital laminae are highly susceptible to damage by
      superoxide anion, produced, for example, by emigrant inflammatory leucocytes.

PMID- 17228596
TI  - Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl
      and its primary metabolite in horses.
AB  - REASONS FOR PERFORMING STUDY: In order to evaluate its potential as an adjunct to
      inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be
      determined. OBJECTIVES: To describe the pharmacokinetics of fentanyl and its
      metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v.
      administration of a single dose to horses that were awake in Treatment 1 and
      anaesthetised with isoflurane in Treatment 2. METHODS: A balanced crossover
      design was used (n = 4/group). During Treatment 1, horses received a single dose
      of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were
      anaesthetised with isoflurane and maintained at 1.2 x minimum alveolar
      anaesthetic concentration. After a 30 min equilibration period, a single dose of
      fentanyl (4 microg/kg bwt, i.v.) was administered to each horse. Plasma fentanyl
      and PMA concentrations were measured at various time points using liquid
      chromatography-mass spectrometry. RESULTS: Anaesthesia with isoflurane
      significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl
      elimination half-life, in awake and anaesthetised horses, was 1 h and volume of
      distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively.
      Anaesthesia with isoflurane also significantly decreased PMA apparent clearance
      and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in
      awake and anaesthetised horses, respectively. CONCLUSIONS AND POTENTIAL
      RELEVANCE: Pharmacokinetics of fentanyl and PMA in horses were substantially
      altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters
      provide information necessary for determination of suitable fentanyl loading and
      infusion doses in awake and isoflurane-anaesthetised horses.

PMID- 17228597
TI  - Innervation and nerve injections of the lumbar spine of the horse: a cadaveric
      study.
AB  - REASONS FOR PERFORMING STUDY: The distal limb innervation of the horse has been
      studied extensively to allow use of local anaesthetic techniques to detect the
      origin of pain in lameness. However, the innervation of the lumbar spine has so
      far been poorly described and a more precise description may assist clinicians to
      localise back pain in the horse. OBJECTIVES: To gain better knowledge of the
      innervation of the lumbar spine and identify salient anatomical features that
      might be used for diagnostic and therapeutic ultrasound guided injections.
      METHODS: The spines of 8 mature horses were dissected. Branches of the dorsal
      rami were followed and their anatomical relationship, with articular facets,
      interspinous structures and muscles, noted. The spines of 3 other horses were
      sectioned transversely and dissected to identify ultrasonographic landmarks of
      the nerves. Six other spines were used to assess the accuracy of ultrasound
      guided injections of the nerves with blue dye. RESULTS: Gross dissections
      confirmed the dual segmental innervation of the articular facets. Each lumbar
      articular facet of 2 lumbar vertebrae was innervated by the medial branch of the
      dorsal ramus exiting from the intervertebral foramen between those vertebrae, but
      also by the branch originating of the dorsal ramus cranial to it. The medial
      branch divided into 2 nerves before exiting the intertransverse space and has
      salient anatomical landmarks which could be identified ultrasonographically. The
      ultrasound guided injection technique appeared to be of an accuracy that would be
      clinically useful. CONCLUSION: The results identified that the salient anatomical
      features of the medial branch of the dorsal ramus, as described in the present
      study, can be used as landmarks for reliable ultrasound-guided injection.
      POTENTIAL RELEVANCE: This study has a clear clinical relevance for development of
      diagnostic and therapeutic injection techniques of the lumbar spine in the horse.

PMID- 17228598
TI  - Racing performance after arthroscopic removal of apical sesamoid fracture
      fragments in Thoroughbred horses age < 2 years: 151 cases (1989--2002).
AB  - REASONS FOR PERFORMING STUDY: Studies on arthroscopic removal of apical proximal
      sesamoid fracture fragments in Thoroughbred (TB) horses age > or = 2 years have
      reported a high success rate. However, there are no reports documenting the
      racing prognosis of TB horses that undergo such surgery as weanlings or
      yearlings. OBJECTIVES: To describe the incidence of apical proximal sesamoid
      fractures in immature TB horses, age < 2 years and determine probability and
      quality of racing performance after arthroscopic removal of such fractures in 151
      TB weanlings and yearlings. METHODS: The medical records of TB horses age < 2
      years that underwent arthroscopic surgery for removal of apical proximal sesamoid
      fracture fragments were reviewed. Follow-up information was obtained from race
      records. Student's t tests were used to compare performance variables of operated
      racehorses to that of their maternal siblings. RESULTS: Ninety-two percent
      (139/151) of fractures occurred in the hindlimbs and 8% (11/151) in the forelimbs
      (fracture of both fore- and hindlimb, n = 1). Horses with forelimb fractures had
      a greatly reduced probability of racing (55%) compared to those with hindlimb
      fractures (86%). Overall, 84% of the horses raced post operatively and had
      performance records similar to that of their maternal siblings, 78% (787/1006) of
      which raced. CONCLUSIONS: Arthroscopic removal of apical proximal sesamoid
      fracture fragments in TB weanlings and yearlings carries an excellent prognosis
      for racing in horses with hindlimb fractures and a reduced prognosis in those
      with forelimb fractures. Medial fractures of the forelimb carry the worst
      prognosis. POTENTIAL RELEVANCE: The determination of prognosis increases
      knowledge on apical sesamoid bone fractures and potential for arthroscopic
      restoration of the ability to race; and enables the value of yearlings for
      subsequent sale to be established.

PMID- 17228599
TI  - Identification of environmental factors affecting the prevalence of insect bite
      hypersensitivity in Shetland ponies and Friesian horses in The Netherlands.
AB  - REASONS FOR PERFORMING STUDY: It is expected that climate and habitat factors
      influence the prevalence of culicoides and, therefore, the prevalence of insect
      bite hypersensitivity (IBH), but very little is described in the literature to
      prove the association of these factors. Prevalence varies widely from 3% in
      certain areas of Great Britain to 60% in certain parts of Australia. OBJECTIVES:
      To describe the influence of environmental factors on the prevalence of IBH in
      Shetland ponies and Friesian horses in The Netherlands. METHODS: Data on 3284
      Shetland and 2824 Friesian mares (n = 6108) were collected in The Netherlands,
      based on 90 regions, according to postal codes. The climate components, amount of
      rainfall, number of warm days, number of cold days, and habitat components of
      soil type and type of vegetation were collected for each region. RESULTS:
      Prevalence of IBH varied widely from 0-71.4% per region. The results showed that
      the environment with low IBH-prevalence had high rainfall, many cold days and few
      warm days per year. Habitats with a low IBH-prevalence were based along the coast
      line. Habitats with increasing prevalence of IBH had soils of clay with heather
      and woody vegetation. Friesian mares had a higher IBH prevalence than Shetland
      mares, which could indicate an effect of genetic background or an effect of year.
      CONCLUSIONS: There is an environmental effect on IBH prevalence within The
      Netherlands, which is caused by climate and habitat factors. POTENTIAL RELEVANCE:
      The results provide a more accurate description of environmental factors and
      their impact on development of IBH; and should help better to understand habitat
      and climate effects, and to distinguish these from other effects, such as animal
      factors (genetics, age or sex).

PMID- 17228600
TI  - Parenteral nutrition in foals: a retrospective study of 45 cases (2000--2004).
AB  - REASONS FOR PERFORMING STUDY: Adequate nutritional support of sick foals in
      critical care is an important aspect of treatment. When enteral feeding is
      contraindicated, parenteral nutrition (PN) provides a source of energy and
      protein. However, no study has critically assessed the use of PN in a large group
      of foals. OBJECTIVE: The administration of PN to clinically ill foals was
      examined retrospectively to determine the effects of PN formulation and variables
      on the incidence of PN-associated complications and outcome. HYPOTHESES: There
      was no effect of PN formula on 1) the occurrence or type of complications; 2) of
      PN formula on outcome; 3) of disease severity on the occurrence or type of
      complications; and 4) of disease severity on outcome. METHODS: Medical records of
      45 foals, presented to the Marion duPont Scott Equine Medical Center, which
      received PN, were reviewed for the years 2000-2004. RESULTS: The indications for
      PN were recumbency, depression or gastrointestinal conditions. Formulation of PN
      was not associated with the development of complications, and there was no
      association of PN formula with patient survival. Disease severity was positively
      associated with the development of PN complications and the occurrence of PN
      complications was associated with an increased risk of nonsurvival. CONCLUSION
      AND POTENTIAL RELEVANCE: The use of lipid-containing PN solutions facilitates the
      delivery of energy to the critically-ill foal without increasing the risk of
      deleterious side effects. Severely ill foals are more prone to develop
      complications associated with PN and to have a poor outcome.

PMID- 17228601
TI  - Ultrasound-guided coxofemoral arthrocentesis in horses.
AB  - REASON FOR PERFORMING STUDY: Coxofemoral joint pain is probably underestimated
      due to difficulties in identifying hip pain. The deep location of the joint and
      proximity of the sciatic nerve make arthrocentesis based on external landmarks a
      difficult and potentially risky procedure in mature horses. OBJECTIVES: To
      describe an ultrasound-guided injection technique of the coxofemoral joint in
      standing horses and to evaluate its accuracy and potential
      difficulties/complications. METHODS: Nine mature horses had both pelvic areas
      prepared for sterile ultrasound examination (3.5 MHz curvilinear probe).
      Coxofemoral joints were located and penetrated at their craniodorsolateral aspect
      under ultrasonographic guidance and injected with sterile contrast medium. A
      standing ventrodorsal radiographic view of each hemipelvis centred on the hip was
      obtained for each horse to assess the injection site. Horses were evaluated for
      10 days following injection for possible complications. RESULTS: Intra-articular
      injection was successful in all 18 joints. The procedure was well tolerated by
      horses under minimal restraint. Mean +/- s.d. needle repositionings required
      before accurate placement was 1.5 +/- 1.3 per joint. Once the needle was in the
      joint, synovial fluid was obtained in 7/18 joints. Minimal periarticular contrast
      medium was detected in 2/18 joints. Mean +/- s.d. ultrasonographic examination
      time required for coxofemoral localisation, accurate needle positioning and
      injection was 4.3 +/- 2.1 min. No complications were observed in the 10 days
      following injection. CONCLUSION: The ultrasound-guided coxofemoral arthrocentesis
      is an accurate, reliable and safe technique that offers a real time evaluation of
      needle introduction into the deep and narrow coxofemoral joint space. POTENTIAL
      RELEVANCE: Although this technique remains to be tested on clinical cases, it is
      a promising tool to facilitate diagnosis of coxofemoral pain, septic arthritis or
      administration of intra-articular medication.

PMID- 17228602
TI  - Bacteraemia in neonatal foals: clinicopathological differences between Gram
      positive and Gram-negative infections, and single organism and mixed infections.
AB  - REASONS FOR PERFORMING STUDY: Treatment for bacteraemia in foals must be started
      before the identity of the causative organism is known. Information aiding
      selection of effective antimicrobials should improve outcome. OBJECTIVES: To
      describe differences in clinical and clinicopathological data and outcome in
      foals with bacteraemia due to different classes of bacteria. METHODS: Records of
      foals with a positive blood culture, age < 10 days and presenting to a university
      hospital 1995-2004, were reviewed. Bacterial culture results, subject details,
      historical information, physical examination findings at admission and
      clinicopathological data generated during the first 48 h of hospitalisation were
      analysed. Results from foals with Gram-positive or Gram-negative organisms,
      single or mixed organism bacteraemias, and with bacteraemia due to 3 commonly
      isolated organisms were compared. RESULTS: Eighty-five foals met the inclusion
      criteria. Gram-negative organisms (n = 59) Gram-positive organisms (n = 13) or
      multiple organisms (n = 19) were cultured from individual foals. Foals with Gram
      negative bacteraemia had lower total white blood cell and lymphocyte counts at
      admission than did those from which only Gram-positive bacteria were cultured.
      Mixed organism bacteraemia was associated with tachycardia, increased serum
      concentrations of sodium, chloride and urea nitrogen, acidosis, respiratory
      distress, recumbency on admission and nonsurvival. Actinobacillus spp. infections
      were associated with leucopenia, neutropenia, lymphopenia and depression on
      hospital admission. CONCLUSIONS AND POTENTIAL RELEVANCE: Recognising particular
      patterns of clinical and clinicopathological findings associated with infection
      with specific groups of bacteria may, in the future, aid antimicrobial selection
      and influence prognosis in bacteraemic foals.

PMID- 17228603
TI  - Equine physiotherapy: a comparative view of the science underlying the
      profession.

PMID- 17228604
TI  - Comments about the importance of behaviour to equine clinicians.

PMID- 17228605
TI  - [Risk management in a regional screening program for breast cancer in the region
      of Lazio, Italy].
AB  - In the Lazio Region, it has been put into effect a plan of clinical Risk
      Management for the Breast Cancer Screening Regional Program (BCSP), involving all
      of the 12 Local Health Units and the Public Health Agency of Lazio (ASP). Being
      the BCSP a health care service, it consists of a perfect integration of health
      care structures, professionals and skills working for the citizens. This program
      originates from an unexpressed health need and leads to a evidence-based health
      benefit. The BCSP provides free breast screening for 700,000 women aged between
      50 and 69 in the Lazio region; the Public Health Agency carries out the clinical
      governance of the BCSP The prevention of errors and incidents represents a
      fundamental basis of governance: it is a contribution to the achievement of
      efficacy in breast cancer screening. The BCSP deals with screening incidents from
      a systemic point of view and actively involves several Local Health Units staff
      going through each step of the whole patient's clinical path, from the
      identification of the target population, to the oncological treatment of positive
      cases. The programme is an integration of different tools: literature research,
      process analysis using the HFMEA methodology and reporting system. The results
      reached so far are the following: the regional severity rating scale, the
      regional Master-List of possible adverse events, occurrence and detection rating
      scale.

PMID- 17228606
TI  - [Occupational exposure to formaldehyde in three pathology departments].
AB  - Although formaldehyde has recently been classified by the IARC as "carcinogenic
      in humans" (class 1), it is still widely used in pathology departments for the
      fixing and conservation of biological tissues. Its use therefore raises the
      question of occupational exposure. The present paper reports the results of an
      environmental monitoring campaign to evaluate pollution by formaldehyde in
      various areas of three pathology departments. Chemi-adsorbent cartridges able to
      adsorb airborne formaldehyde were used to detect the substance. Quantitative
      determination of the formaldehyde was carried out by means of liquid
      chromatography (HPLC). The concentrations of airborne formaldehyde in the areas
      monitored were fairly modest, being below the limits of indoor concentration
      proposed by the OSHA. In one of the three departments, however these limits were
      exceeded in 40% of the samples taken in the room used for the storage of
      containers. As yet, in spite of the recent class 1 classification by the IARC, no
      provisions have been made to ban the use of formaldehyde. It is therefore
      essential to draw up environmental monitoring programmes in order to evaluate
      occupational exposure and to assess the efficacy of any preventive measures
      adopted.

PMID- 17228607
TI  - [Environmental hygiene of the surgery suites for the control of surgical wound
      infection: Italian legislation and international guidelines].
AB  - Aim of the study is to describe the application of surgical site infection (SSI)
      control procedures in general surgery operating rooms of Piedmont region
      hospitals. A specific data collection form was designed to record information. 54
      questionnaires were compiled. Piedmont legislation related to operating rooms'
      equipment is obeyed in more than 90% of hospitals. Nevertheless, there are some
      critical aspects than could be risk factors for SSI or that are not useful in
      order to prevent them: use of UV radiation (11.3%), use of tacky mats at the
      entrance of the operating room (5.7%), special cleaning of operating rooms after
      contaminated or dirty operations (73.6%) and routine environmental sampling (10%)
      that is strongly recommended by ISPESL guideline in disagreement with
      international recommendations. Steam autoclave is used for surgical instruments
      sterilization by 100% of hospitals, but only 50% of them performs an annual
      validation of both autoclave performance and sterilization procedures. The study
      gave useful information in order to promote some structural modifications and
      personnel education for efficacious SSI prevention and control.

PMID- 17228608
TI  - [Exposure to traffic noise and effects on attention].
AB  - This study was aimed to evaluate if workers exposed to environmental stressors,
      including the urban traffic noise, might show significant differences compared to
      a control group in neuro-psychological and emotional profile as well as
      neurophysiological functions. In particular if these differences could be
      evidenced by the application of the "oddball paradigm" for event related
      potential P300 component. The study consisted of the following examinations: (1)
      exposed workers vs. controls under the odd-ball paradigm and the Stroop test in
      baseline condition; (2) amplitude and latency ofP300 (in baseline condition and
      after administration of acute urban traffic noise and Stroop test). The research
      was carried on a sample of 81 volunteers: 39 workers exposed to environmental
      stressors and 42 controls. The phonometric measurements showed mean levels of
      noise due urban traffic like 74 dBAeq. In baseline condition significative
      differences in exposed workers vs. control were found in Raven's Matrices PM 38
      (p = 0.002) and Arithmetic reasoning from WAIS-R (p = 0.0024). Attention
      capacities as measured by Digit Span Forward and Visual Search, emotional
      functioning as measured by state- and trait-anxiety test and mood profile were
      not different in the two groups. Either in baseline condition or after acute
      stimuli no significant changes were found in two groups concerning the odd-ball
      paradigm. Exposed workers showed a higher execution time at Stroop test compared
      to controls (p = 0.047). No differences were found in the number of errors at the
      Stroop test. Before the acute stimulus, P300 amplitude was significant higher in
      the exposed workers than in controls (p = 0.002) while the latency was not
      different between two groups. Both noise (p = 0.001) and Stroop test (p = 0.002)
      stimulation increased the P300 latency of the whole sample, without significant
      differences between exposed workers and controls. A significative decrease of
      P300 amplitude due noise both in the exposed workers (p = 0.001) and in controls
      (p = 0.012) was found, without significant difference between the two groups.
      These results are interpreted as follows: (1) there are chronic effects on
      cognitive functioning in the exposed group vs. controls in baseline condition,
      like showed by significant differences in Raven PM38 and WAIS-R; (2) the exposed
      workers have a smaller cognitive flexibility, as shown by the Stroop test
      results; (3) in baseline condition the greater P300 amplitude in exposed workers
      reflect a greater division of attentive resources vs. controls, probably linked
      to the chronic stimulation by environmental stressors, especially noise, to which
      these workers are exposed; (4) the effects on P300 latency and amplitude can
      document the physiological response both in the exposed and not exposed to the
      acute stimulus and that the lack of significative differences in P300 latency and
      amplitude may be due to adaptative response to acute stimuli in exposed too. Our
      results allow us to consider that in workers exposed to urban stressor, such as
      noise, there are effects on cognitive functioning, especially on attention,
      without auditory damages. The valuation of P300 might represent a valid
      diagnostic instrument to evaluate the effects on cognitive functions especially
      on attention, in workers chronically and acutely exposed to urban stressors.

PMID- 17228609
TI  - [Results of the evaluation of environmental technological risk of an Italian
      region (Puglia)].
AB  - In order to plan a correct planning and a realization of interventions to support
      Regional Environmental Authority, results of "Technological Risk" methodology
      applied in a Italian region (Puglia) are reported. In this paper two main risk
      factors has been evaluated (high risk activities, areas with environmental crisis
      high risk) and determined indicators able to describe, in case of accident or
      anomalous event, potential interactions in the normal industrial process. Than
      has been described operative phases to consent risk factors evaluation and their
      evolution, considering also pressures on the environment identified by other
      issues. Some themes were in detail studied through territorial analysis and set
      of rules. This work enables to carry out a specific database for factories
      subject to "substantial risk" and finally was completed data processing with
      thematic maps and statistic analysis.

PMID- 17228610
TI  - [Pre-adolescents and sport: results of a health survey in some secondary schools
      of Brianza].
AB  - This study is aimed at assessing time dedicated to, motivation and involvement in
      physical activity on behalf of pre-adolescents. 802 students (49.3% boys and
      50.7% girls; mean age: 12.6) attending 43 classes of 11 Brianza's post-elementary
      schools. A questionnaire was prepared and administered to the involved sample.
      Classes took part in this study through randomized selection and data were
      analyzed using program Epi Info 6. Most of the respondents (60.1%) stay involved
      in sport because "it makes me feel good" and 32.4% because sport is "enjoyable
      and entertaining". Pre-adolescents chose the sport in which they become engaged
      on the basis of personal inclination (40%), in order to share experiences and
      their free time with friends (15.4%); 13.7% declare to prefer sport to be
      practiced in team. (13.7%). The most practiced sport are: football (51.3% boys,
      4.5% girls), volley (3.9%-36.4%), dance (0.8%-25.2%) e swimming (9.4%-14%). 80.8%
      in the sample practice physical activity in settings outside schools and, among
      these, 51.7% dedicate three or more hours weekly to extra-school activities.
      There are significant differences (p < 0.05) between males' and females'
      engagement in physical activity (mean value: 4.1 hours; males: 4.6 h, females:
      3.5 h). Among pre-teens, 18% declare to be physically inactive at all; 15.7% do
      not take part in sport activities because afraid to be bullied or shamed by
      peers. Research show that males are significantly more involved in physical
      activity than females.

PMID- 17228611
TI  - [Working reinstatement and mental health].
AB  - Mental illness, as anxiety, schizophrenia, obsessive-compulsive disorders,
      anorexia, have a huge impact on any working population. These disorders are a
      medical and social reality in strong increasing and they represent a great public
      interest. People suffering from a mental illness experience many inconveniences:
      a reduced possibility in choosing of the type of job, the necessity of a support,
      the difficulty in changing job, a reduction of the working hours, discriminations
      and abuse. This study explored the role of work in enhancing the economic and
      social integration of people with mental disorders. The importance of addressing
      specific issues (supported employment, vocational rehabilitation) related to the
      employment of persons with mental health problems has also been recognized.

PMID- 17228613
TI  - [Health certification requested for admission to degree courses in Italian
      university medical schools].
AB  - Prior to enrollment in degree courses in Italian university medical schools
      students are required to undergo health tests and preventive measures. The aim of
      this study was to census and assess the health certification required by Italian
      universities. Information was collected from course admission notices published
      on the university websites. Most universities requested health certificates for
      the academic year 2005-2006. Requirements usually focused on the risk of
      tuberculosis and hepatitis B for students enrolled in degree courses in medicine
      and surgery and in dentistry and dental prosthetics. Additional certification
      concerning physical and mental well being suited to specific tasks was also
      required for courses for the health professions of nurses, midwives,
      rehabilitation, technical and health prevention staff The request of several
      universities for antituberculosis vaccination clashed with legislation currently
      in force. Most universities did not notify the subsequent requirement for
      certification concerning physical and mental wellbeing on the website admissions
      list. The survey showed that Italian universities adopt different criteria in
      requesting certifications and different terms and conditions. In addition,
      requirements were often not updated. Competent university medical staff should be
      consulted to define what health certification is required from students for
      admission to different courses in university medical schools.

PMID- 17228612
TI  - [Tobacco smoking among medical students of the University of Milano, Italy].
AB  - In order to evaluate smoking habits among the future medical class an anonymous
      questionnaire about tobacco smoking was submitted to 822 students of the
      University of Milano in six academic years, from 1998/99 to 2003/04. A total of
      184 students (22.4%) were smoker 463 (56.3%) had never smoked and 161 (19.6%) had
      previously smoked. More than half of these last had quit smoking during the
      university years. Smoking habits resulted influenced by the habits in the family
      (parents and brothers) and among the friends. Anti-smoking campaigns among
      medical students are needed taking into account their future role in health
      promotion and in prevention of tobacco smoking and its consequences.

PMID- 17228615
TI  - Population review of 2004 and 2005: England and Wales.
AB  - This article outlines the main features of the population of England and Wales in
      2005. Where 2005 figures have not yet been published, data for 2004 are given.

PMID- 17228614
TI  - Recommendation and report on the death penalty and persons with mental
      disabilities.

PMID- 17228616
TI  - The 2007 Census Test: a major step towards the 2011 Census.
AB  - The Office for National Statistics (ONS) is planning a major Census field test in
      2007. It will form part of the planning and testing programme leading to up the
      next Census of Population for England and Wales in 2011, which will also include
      a Rehearsal in 2009. The 2007 Test will be a large-scale test in five local
      authority (LA) areas selected to reflect a range of field conditions, covering
      some 100,000 households in total. Within England the Test will cover parts of
      Bath and North East Somerset, Camden, Liverpool and Stoke-on-Trent. In Wales the
      Test will take place in Carmarthenshire. The selected LAs have been chosen to
      provide a varied cross-section of the population and types of housing that would
      be covered in a full census. This article sets out the main aims for the Test and
      describes the design and location of the sampled areas and the basis for their
      selection. It goes on to detail the ways (previously reported in Population Trend
      1251) in which the ONS Census team and the LAs involved are working in
      partnership in planning the census enumeration with the long-term view of
      improving overall census coverage and user confidence in the results. The article
      notes that decisions on the topics to be covered in the 2007 Test have only
      recently been decided, and concludes with an overview of the qustions to be
      included in the 2007 Test questionnaire.

PMID- 17228617
TI  - Nicholson pledges to devolve 90pc of resources to local NHS.

PMID- 17228618
TI  - Special measures. In control and ready to share: hope emerges from tragedy.

PMID- 17228619
TI  - On targets.

PMID- 17228620
TI  - 'The only thing you can't predict is where it will go'. An interview with Cliff
      Prior.

PMID- 17228621
TI  - Barometer. Public health Dec 2006.

PMID- 17228622
TI  - Healthcare reform. Is the NHS ready for US business guru's strategy?
AB  - The central argument of the new book by renowned US academics Michael Porter and
      Elizabeth Olmsted Teisberg is that the US health system is broken because rather
      than improving quality and efficiency, it focuses on budgetary battles. HSJ
      gathered together six leading healthcare insiders to discuss whether his
      diagnosis is applicable to the NHS. Nick Edwards was there.

PMID- 17228623
TI  - HSJ Awards. Acute healthcare organisation of the year. Winner: Heart of England
      Foundation Trust.

PMID- 17228624
TI  - HSJ Awards. Primary care organisation of the year. Winner: Oldham PCT.

PMID- 17228625
TI  - HSJ Awards. Chronic disease management. Winner: South Sefton PCT.

PMID- 17228626
TI  - HSJ Awards. Clinical service redesign. Winner: Croydon PCT.

PMID- 17228627
TI  - HSJ Awards. Good corporate citizenship. Winner: Newham University Hospital Trust.

PMID- 17228628
TI  - HSJ Awards. Implementing NICE guidance. Winner: NHS Greater Glasgow and Clyde.

PMID- 17228630
TI  - HSJ Awards. Improving patient access. Winner: NHS Forth Valley.

PMID- 17228629
TI  - HSJ Awards. Improving care with e-technology. Winner: South Staffordshire
      Healthcare Foundation Trust.

PMID- 17228631
TI  - HSJ Awards. Information-based decision making. Winner: Croydon PCT.

PMID- 17228633
TI  - HSJ Awards. Patient-centred care. Winner: Croydon PCT.

PMID- 17228632
TI  - HSJ Awards. Mental health innovation. Winner: Avon and Wilts Mental Health
      Partnership Trust.

PMID- 17228634
TI  - HSJ Awards. Patient safety. Winner: Lancashire Care Trust.

PMID- 17228635
TI  - HSJ Awards. Primary care innovation. Winner: Croydon PCT.

PMID- 17228636
TI  - HSJ Awards. Recruitment and retention. Winner: Newham University Hospital Trust.

PMID- 17228637
TI  - HSJ Awards. Reducing health inequalities. Winner: Sandwell PCT.

PMID- 17228638
TI  - HSJ Awards. Skills development. Winner: NHS West Midlands.

PMID- 17228639
TI  - Standard setting. A dip into quality improvement pot reveals star ideas.

PMID- 17228640
TI  - Leadership. Peak practice.

PMID- 17228641
TI  - [Morphometry of the recurrent laryngeal nerves of the rat].
AB  - In mammals the recurrent laryngeal nerves are dissimilar in length between both
      sides. This asymmetry involves different time of arrival of the stimulus to the
      laryngeal musculature controlled by each nerve. Thus, several explanations have
      been addressed to elucidate the closest of the glottis at the same time despite
      the unlike length of the nerves. However, previous works on the topic lack of
      several important data. The present study compares, in two groups of 10 and 6
      rats, the length and the composition of myelinated fibers in the recurrent
      laryngeal nerves of both sides, by means of light microscopy and a computerized
      morphometric analysis. The results show a mean difference of 0,84 cm longer the
      left than the right recurrent laryngeal nerve. No statistical differences were
      observed in the number of myelinated fibers between both sides. However, the
      myelinated fibers of the right side were statistically bigger in diameter than
      the fibers of the left side. The data are discussed in the context of the
      mechanisms for the compensation of the dissimilar length of both recurrent
      laryngeal nerves.

PMID- 17228642
TI  - [Comparison between 18F-FDG PET and conventional imaging techniques (CT SCAN and
      MRI) in the diagnosis of head and neck tumor suspicion of recurrence].
AB  - BACKGROUND: This study aimed to assess the results obtained with the positron
      emission tomography (PET) and conventional anatomic imaging methods (CT scan and
      MRI) in the diagnosis of suspicion of tumor recurrence in head and neck cancers.
      METHODS: Thirty patients with suspicion of tumor recurrence due to head and neck
      cancers were reviewed retrospectively. Consequently, 34 PET studies were
      performed. The images were obtained in the PET Institute of Madrid. They were
      interpreted by visual and semiquantitative analysis. The results were confirmed
      with clinical follow-up, response to treatment or with histological studies in
      some cases. RESULTS: Sensitivity and specificity of the PET were 95.6% and 81.8%
      respectively, while it was 65% and 80% for the CT scan/MRI. CONCLUSIONS: We can
      conclude that PET provides better results than conventional imaging techniques in
      the detection of head and neck cancer recurrence.

PMID- 17228643
TI  - [Benign paroxysmal positional vertigo of the horizontal semicircular canal].
AB  - OBJECTIVE: Assesment of 8 new cases of benign paroxysmal positional vertigo of
      the horizontal semicircular canal (BPPV-HC), since this variant of benign
      positional vertigo occurs rarely. An oculographic study of features in the
      positional response was carried out. Electrooculograpy (EOG) allows an exhaustive
      study of positional nystagmus. MATERIAL AND METHODS: We have studied
      retrospectively 8 patients with BPPV-HC and positive head rotation manoeuvre
      registered by EOG techniques. Possible alterations in other EOG tests in the
      group of patients were analyzed. RESULTS: Most of the patients (7/8) expressed
      bilateral horizontal geotropic changing-direction nystagmus. One patient
      exhibited apogeotropic horizontal nystagmus. 5/8 cases showed caloric
      hypofunction. CONCLUSIONS: We have proven that BPPV-HC is an uncommon disorder.
      In most of the cases, provocative manoeuver generates bilateral horizontal
      geotropic changing-direction nystagmus that probably is due to canalitiasis of
      the horizontal semicircular canal. The rest, a few cases, exhibit apogeotropic
      horizontal response that can be secondary to cupulolitiasis or location particles
      in the anterior portion of the horizontal canal. A caloric test showed abnormal
      in many and can help to locatize the affected ear.

PMID- 17228644
TI  - [Petrous bone fracture. Our experience: 1999-2004].
AB  - OBJECTIVE: To review the petrous bone fractures during the last five years (1999
      2004) in our hospital, its manage, control, and analysis onf the associated
      factors. To analyse the managing protocoles and current bibliography. MATERIAL
      AND METHODS: We review 266 temporal bone fractures, 74 with petrous bone
      association. We analyse these fractures by sex distribution, injurie severity,
      otorhinolaryngological clinical findings, production mechanism and radiological
      findings. The cases are discussed and compared with current bibliography.
      CONCLUSIONS: Petrous bone fractures must be always suspected in patients with
      head trauma, specially if it associates severity and otorrhagia. It is necessary
      a deep colaboration between neurosurgeons, radiologists and
      otorhinolaryngologists to obtain a good management, control and follow up of the
      patients.

PMID- 17228646
TI  - [Second primary tumors in head and neck cancer].
AB  - INTRODUCTION: The development of second primary tumors (SPT) in patients with
      head and neck squamous cell carcinoma (HNSCC) has become an increasingly
      important factor in clinical treatment decisions. PURPOSE: To define favourable
      clinical characteristics for overall survival, in patients with SP head and neck
      cancer. MATERIAL AND METHOD: Records of 633 patients with SCC treated from 1984
      to 2004 were reviewed to describe clinical characteristics of the SPT. RESULTS:
      The overall incidence of SPT was 11%. The incidence of the index tumors was as
      follows: supraglottic cancer 21% and oral cancer 16%. The most common SPT
      occurred in head and neck area in 47%, lung in 32% and esophagus in 11%. Second
      primary was associated with a poor 5 years survival in patients with HN-SCC (23
      versus 53% in control group). CONCLUSION: Because of the high rate of second
      primary tumors, protocols including chemoprophylaxis should be investigated.
      Prevention and early detection are indicated.

PMID- 17228645
TI  - [Subjetive benefits and limitations in relation with the cochlear implant
      reported by adolescent and adult patients].
AB  - OBJECTIVE: To identify the subjetive benefits and limitations of the pre and
      postlingually adolescent and adult patients of the cochlear implants program at
      Clinical Hospital San Cecilio (Granada). MATERIAL AND METHODS: Cross-sectional
      study of 60 pre and postlingually deaf patients who received cochlear implant
      with more than 12 years and at least a year of experience. A open-ended
      questionnaire was used to value their subjetive experience. A descriptive
      analysis was made and we applied the square Chi and Mann-Withney tests. RESULTS:
      The average implant usage per day was greater in the postlingually patients (14.6
      hours) that in the prelingually (10.4 hours). Between the acoustic benefits, both
      more frequent were the perception of environmental sounds and the possibility of
      to converse easier, specially with one or two persons. The benefit more indicated
      by the patients was the improvement in its mood. The perception in noise
      situations was the difficulty more indicated by all patients. The problems, in
      relation with the device, more frequently indicated were the size and the weight.
      CONCLUSION: the cochlear implant provides subjetive benefits to the patients that
      complement their improvement in perception of the oral language and facilitate
      the re/integration of the deaf patients at his work and in his social life.
      Therefore, the speech perception tests must be complemented with another type of
      materials to value the result of the cochlear implant and then we will can to
      speak of success or failure.

PMID- 17228648
TI  - [Multifocal localized amyloidosis in a pediatric patient].
AB  - Amyloidosis of the upper airway is rare in the pediatric age group. We present a
      primary amyloidosis in the nasopharynx and nasal cavity in a 14-year-old girl.
      The symptoms were nasal obstruction and mucoid discharge. The diagnostic was
      revealed by histologycal analysis obtained from local surgical excision.

PMID- 17228647
TI  - [Montgomery salivary bypass tube: a simple solution for pharyngocutaneous
      fistulas].
AB  - INTRODUCTION: The pharyngocutaneous fistulas (PCF) are among the complications
      surgeons and nursing personnel fear the most due to their complexity to prevent
      and/or cure them. Montgomery salivary bypass tube is an effective therapeutic
      option in the treatment of the PCF following laryngectomy. The aim of our study
      was to describe our experience with salivary bypass in the treatment of the PCF.
      METHODS: This was a retrospective analysis of pharyngocutaneous fistulas in 21
      patients in whom total laryngectomy was performed for squamous cell carcinoma of
      the larynx or hypopharynx (January 1999-December 2005). We determinate the
      overall efficacy of the Montgomery salivary bypass tube in the treatment of the
      PCF. RESULTS: A pharyngocutaneous fistula developed within a mean time of 7 days
      from surgery (from 2nd to 20th day). Montgomery salivary bypass tube was the
      therapeutic option in all these PCF.12 patients required local anesthesia to
      introduce the tube and in 9 patients the insertion method was with general
      anesthesia with direct vision of the hypopharynx. The mean healing time was 26
      days, except in one case. This PCF achieved spontaneous closure with local wound
      care after the bypass was removed. CONCLUSIONS: The observed results corroborated
      the relevance of Montgomery salivary bypass tube as an important therapeutic
      option in the treatment of the PCF. There was no need of surgical treatment.

PMID- 17228649
TI  - [Migration and extrusion from the upper digestive tract to the skin of the neck
      of a foreign body (fish bone)].
AB  - Foreign bodies ingestion is a common problem seen at emergency rooms and mostly
      involved are fish and chicken bones. The diagnosis can be difficult because of
      the age of the patient (children and older patients with dental prosthesis). The
      shape of the foreign body leds to the course of the pathology, with possible
      mayor complications like migration into the fascial spaces of the neck,
      retropharyngeal abscess and perforation of the pharynx or esophagus which have
      the potential to cause morbidity and mortality. We present a 88-year-old lady who
      swallowed a 3 cm linear sharp fish bone which migrated from the pharynx to the
      skin of the neck, surfaced through a fistulous orifice and threw out six weeks
      later. No intervention was needed. A discussion of the management of migrated
      foreign bodies follows.

PMID- 17228650
TI  - [Studies on cultivation measures of Angelica dahurica].
AB  - OBJECTIVE: To evaluate the effect of seedingtime, density of crop and
      fertilization on the yield of Angelica dahurica. METHOD: Use weighing method to
      measure the output of A. dahurica. RESULT: The highest yield of seeding-time is
      8373 kg/hm' on April 20, which is considerably different compared with April 5
      and May 5; the highest yield of the density is 9300 kg/hm2 on 330,000 plants/hm2;
      the yield of fertilization tests all are considerable higher than that of the
      contrast. CONCLUSION: The appropriate seeingtime of A. dahurica is the first or
      second ten days of April, the appropriate density is 330,000 plants/hm2, and the
      appropriate amount of fertilization is N24P20, i.e pure N 360 kg and P20, 300 kg
      per hectare.

PMID- 17228651
TI  - [Tissue culture and rapid propagation of Trichosanthes kirilowii].
AB  - OBJECTIVE: To study tissue culture of Trichosanthes kirilowii, and establish the
      technique of rapid propagation. METHODS: Cluster buds were induced from stem tip
      and stem with axillary bud, calluses were induced from stems and leaves. RESULTS:
      Cluster buds could be induced on both the bud and axillary bud from 2-years-old
      tuber of Trichosanthes kirilowii with MS medium containing 2 mg/L BA and 0.5 
      0.05 mg/L NAA. The roots could be induced with MS + 0.1 mg/L NAA + 0.2 mg/L IBA.
      The seedling with roots could be transplanted after domestication, and achieved
      the rapid seedling propagation. Calluses could be induced from the stems and
      leaves with MS + 4 mg/L BA + 0.5 mg/L NAA, and the calluses then could be
      differentiated into seedlings without root. CONCLUSION: The male and female
      seedlings of Trichosanthes kirilowii can be propagated largely using stem tip or
      axillary bud in short period. The technique of rapid propagation on Trichosanthes
      kirilowii have a high benefit and low costs.

PMID- 17228652
TI  - [Study on the comparison of polysaccharides in Ginkgo biloba leaves].
AB  - OBJECTIVE: To determine the suitable tree's age, tree's sex and gathering seasons
      for Ginkgo biloba leaves. METHODS: The twelve different polysaccharides were
      obtained by extracting and precipitating from Ginkgo biloba leaves and to see if
      there were differences among them. The concentration of Ginkgo biloba leaf
      polysaccharides with the highest gain ratio will be determined by HPLC. RESULT:
      The average gain ratio of Ginkgo biloba leaf polysaccharides was 4.29%, among
      them the gain ratio of 10-years old female Ginkgo biloba leaf collected in the
      last ten days of September was the highests, its polysaccharides concentration
      was 61.5% with RSD = 2.5% (n = 6). CONCLUSION: The gain ratios were different in
      different Ginkgo biloba leaves and the changing rules provide scientific basis
      for the GAP of medicinal plants.

PMID- 17228653
TI  - [Comparation of constitutions between raw Psoralea corylifolia L. and processed
      one].
AB  - OBJECTIVE: To study the processing material foundation of Psoralea corylfolia L.
      and compare the content of psoralen, isopsoralen and microelement between raw
      Psoralea corylifolia L. and processed one. METHODS: The content of psoralen,
      isopsoralen and microelement were obtained by HPLC-gradient elution and ICP-AES.
      RESULTS: The content of psoralen, isopsoralen and microelement Mn, Ca, Mg, Fe, Zn
      were raising, but the change of that of microelement Cu was not obvious.
      CONCLUSION: The content of effective composition of Psoralea corylifolia L. is
      raised by Lei-Gong method and the biological activity is improved simultaneously.

PMID- 17228654
TI  - [Molecular characteristic marker method of 27 breeds of common Umbelliferae
      Chinese herb medicinal plants by sequencing rDNA].
AB  - OBJECTIVE: To probe a molecular marker method of accrediting fingerprinting of 27
      kinds of common Umbelliferae Chinese herb medicinal plants by sequencing rDNA.
      METHOD: The rDNA sequences of the 27 breeds of common Umbelliferae Chinese herb
      medicinal plants were amplified, and were digested by restriction endonuclease,
      and were seperated via polypropylene electrophoresis, at last 6 breeds of them
      were sequenced. RESULTS: The rDNA sequence fragment we gained concluded ITS1,
      ITS2, 5.8S complete sequence and 18S, 26S part sequence. On the electrophoresis
      map of PCR products digested by restriction endonuclease MSP I, 27 breeds
      appeared 16 kinds of characteristic map, 11 of them differ from others; and PCR
      products digested by restriction endonuclease HaeIII, there appeared 5 kinds of
      characteristic map among 27 breeds, 3 of them differ from others. The sequenced
      result of 6 breeds showed genes whose length extented from 652bp to 656bp were
      acquired. These sequences of 3 breeds which showed the same electrophoresis map
      after digested by restriction endonuclease HaeIII exhibited great similarity
      according to similar phylogenetic tree constructed on rDNA sequence. CONCLUSION:
      The rDNA sequence character is effective molecular marker for classifying the
      different Umbellerae Chinese herb medicinal plants. And the method of sequencing
      rDNA surpassed that of restriction fragment long polymorphism (RFLP).

PMID- 17228655
TI  - [Identification of Magnolia biondii Pamp by X-Ray diffraction Fourier pattern
      method].
AB  - OBJECTIVE: To establish a new identification and analysis method of Magnolia
      biondii Pamp. METHODS: Powder X-Ray diffraction fourier fingerprint pattern
      method. RESULT: Experiment and analysis were carried out on five samples. The
      standard X-Ray diffraction Fourier fingerprint pattern method and characteristic
      diffraction peaks of Magnolia biondii Pamp were obtained. CONCLUSION: The method
      can be used for the identification of Magnolia biondii Pamp.

PMID- 17228656
TI  - [Study on the chemical constituents of the leaves from Crataegus pinnatifida Bge.
      var. major N. E. Br].
AB  - OBJECTIVE: to study the chemical components of the leaves from Crataegus
      pinnatifida Bge. var major N. E. Br. METHODS: Constituents were isolated by using
      silica gel, porous resin, Sephadex LH-20 chromatographic technique, etc. Their
      structures were elucidated by chemical and spectroscopic methods. RESULTS:
      Fourteen compounds were identified as quercetin (1), hyperoside (2), quercetin 3
      O-beta-D-glucoside (3), rutin (4), quercetin 3-O-[alpha-L-rhamnopyranosyl(1-4)
      alpha-L-rhamnopyranosyl-(1-6)-beta-glucopyranoside] (5), vitexin (6), 6"-O-acetyl
      vitexin (7), vitexin 2"-O-rhamnoside (8), vitexin 4"-O-glucoside (9), chlorogenic
      acid (10), ursolic acid (11), beta-sitosterol (12), beta-daucosterol (13), n
      triacontanol (14). CONCLUSION: Compound 5 and 14 were isolated from Crataegus L.
      for the first time.

PMID- 17228657
TI  - [Study on steroidal compounds from Dioscorea zingiberensis].
AB  - OBJECTIVE: To study the chemical constituents of Dioscorea zingiberensis. METHOD:
      Manifold chromatography methods were used to separate the chemical constituents,
      and the chemical stuctures were determined by spectral analyses. RESULT: 6
      compounds were isolated from Dioscorea zingiberensis and identified as deltonin,
      protodeltonin, zingiberensis newsaponin, dioscin, 3-O-[beta-D-glucopyranosyl(1 -
      > 4)]-beta-D-glucopyranosyl-diosgenin, diosgenin. CONCLUSION: Deltonin and
      protodeltonin were isolated from this plant for the first time.

PMID- 17228658
TI  - [Study on steroidal saponins of Dioscorea septemloba thunb].
AB  - OBJECTIVE: To isolate and identify steroidal saponins from the rhizomes of
      Dioscorea septemloba Thunb. METHODS: The compounds were isolated by solvent
      extraction, column chromatography on silica gel and ODS, and their structures
      were elucidated on the base of chemical and spectral analyses. RESULTS: Three
      steroidal saponins were isolated from the rhizomes of Dioscorea septemloba Thunb,
      and their structures were detemined as dioscin (I), protodioscin (II),
      protogracillin (III). CONCLUSION: Compound II and III were obtained from the
      rhizomes of Dioscorea septemloba Thunb for the first time.

PMID- 17228659
TI  - [Comparison of volatile oil chromatographic fingerprints of rhizoma curcumae
      longae and rhizoma wenyujin concisum].
AB  - To explore the same and difference of chemical components between the
      chromatographic fingerprints of volatile oil of Rhizoma Curcumae Longae and
      Rhizoma Wenyujin Concisum, the chromatographic/spectroscopic data of fingerprints
      were comparative analyzed using modified window target-testing factor analysis
      method. The results of comparisons showed that ten chemical components present in
      Rhizoma Curcumae Longae are absent in Rhizoma Wenyujin Concisum, while nine
      chemical components are present in Rhizoma Wenyujin Concisum but absent in
      Rhizoma Curcumae Longae. Also, nine common components are both present in Rhizoma
      Curcumae Longae and Rhizoma Wenyujin Concisum.

PMID- 17228660
TI  - [Studies on the chemical constituents of hypogeal part from Limonium bicolor].
AB  - OBJECTIVE: To study chemical constituents of hypogeal part from Limonium bicolor.
      METHODS: Column chromatography and spectral analysis were usded to isolate and
      identify the constituents, respectively. RESULTS: Four compounds were isolated
      and identified as beta-sitosterol (1), gallic acid (2), luteolin (3), quercetin
      (4). Some white grease was obtained, and nine constituents were identified by GC
      MS elementarily. They were 2,4-dimethyl-heptene (5), ethylbenzene (6), O-xylene
      (7), styrene (8), hexadecanoic acid etylester (9), 9,12-octodecadienoic acid
      etylester (10), diisooctyl phthalate (11), alpha-amyrin (12), beta-amyrin (13),
      respectively. CONCLUSION: Compound 1 is isolated from Limonium bicolor and
      compounds 5-13 are extracted from Limonium Mill for the first time.

PMID- 17228661
TI  - [The effect of ligustrazine on cells proliferation in cortex and striatum after
      focal cerebral ischemia in adult rats].
AB  - OBJECTIVE: To explore the effect of Ligustrazine on cells proliferation in cortex
      and striatum after focal cerebral ischemia in adult rats. METHODS: Focal cerebral
      ischemia was induced by left middle cerebral artery occlusion (MCAO) with suture
      method. Two hours later, injection of Ligustrazine (80 mg/kg, 1 time/d) was
      performed peritoneally. Four hours after the ischemia, 5-bromodeoxyuridine (BrdU)
      (50 mg/kg, 1 time/d) was injected peritoneally. At 7d, 14d and 21d after
      ischemia, BrdU-Labeled cells in the cortex and striatum were observed by
      immunohistochemical staining. RESULTS: In ischemia model group, at 7 day, BrdU
      labeled cells were observed in the ipsilateral cortex and striatum. With the
      prolongation of ischemia, the number of BrdU-labeled cells increased, reached the
      peak at 21d. In Ligustrazine group, BrdU-labeded cells were observed with an
      intense distribution in ischemic penumbra of the cortex and striatum. With the
      prolongation of ischemia, the number of BrdU-labeled cells increased
      significantly at 14d, and reached the peak at 21d. The numbers of BrdU-labeled
      cells at 7d, 14d and 21d were more than those in ischemia model group
      respectively. CONCLUSION: Ligustrazine increase the proliferated cells in the
      cortex and striatum after focal cerebral ischemia in adult rats. The results
      suggest that it may be useful for promoting self-repair after ischemia.

PMID- 17228662
TI  - [Primary research on anti-tumor activity of panaxadiol fatty acid esters].
AB  - For making use of Ginseng resources and finding new anti-tumor drugs, the anti
      tumor activity of three kinds of new panaxadiol fatty acid ester derivates: 3beta
      acetoxy panaxadiol (I), 3beta-palmitic acid aceloxy panaxadiol (II), 3beta
      octadecanoic acid aceloxy panaxadiol (Ill) and panaxaiol were compared through
      the method of cell stain and counting. Tumor cell was Vero cell line. Positive
      control was 5-FU. Blank was RPM11640 culture medium. Negative control was
      RPM11640 culture medium and the solvent for subjected drugs. The result showed
      that compound I had the strongest anti-tumor activity, second was panaxadiol, II
      and III had the same and the weakest antitumor activity. Furthermore, the anti
      tumor activities of panaxadiol fatty acid ester derivates showed positive
      correlation with subjects' concentrations, but no relationship with molecular
      weight of fatty acid.

PMID- 17228663
TI  - [The influence of Solanum lyratum Thunb extract on apoptosis and the expression
      of fas/fasL genes in Hela cells].
AB  - OBJECTIVE: To explore the effects of Solanum lyratum Thunb (SL) extract on the
      apoptosis and the expression of fas and fasL genes in Hela cells. METHODS: The
      proliferation inhibitory rate was evaluated by MTF assay. Induction of cell
      apoptosis rate was determined by flow cytometry. The expression of Fas protein
      was detected by two-step immunhistochemical staining. The expression of fas and
      fasL mRNA was detected by semi-quantitive RT-PCR. RESULTS: SL extract displayed
      strong proliferation inhibitory effect in a dose-and-time-dependent manner
      against Hela cell. The rate of apoptosis was increased obviously. The expression
      of fas mRNA and protein was increased significantly, and fasL mRNA was decreased
      markedly. CONCLUSION: SL can induce apoptosis by up-regulating expression of fas
      and fasL genes, and inhibit the development of Hela cells.

PMID- 17228664
TI  - [The experimental research about the effect of Prunella vulgaris L. on Raji cells
      growth and expression of apoptosis related protein].
AB  - OBJECTIVE: To investigate the anti-lymphoma effect of Prunella vulgaris L. in
      order to offer exprimental data for the treatment of lymphoma with Prunella
      vulgaris L. in clinic. METHODS: Effect of Prunella vulgaris L. injection on
      inhibition ratio of cell growth of Raji cells and IC50 were tested by MTT assay.
      The growth curve line of Raji cells was drawn also by MTT assay. The cellular
      morphology was observed by invert microscope, Giemas staining and MTT assay. The
      expression of apoptosis related protein bcl-2, bax was measured by
      immunocytochemistry and the quantitative analysis was made with figure analysis
      system. RESULTS: 1. Prunella vulgaris L. could obviously suppress the cell
      proliferation of Raji cells in a concentration-dependent manner (r = 0.97). The
      IC50 was 0.118 mg/ml. 2. After Raji cells was reacted with injection of Prunella
      vulgaris L. (50 mg/ml) , the morphlogical of apoptosis were observed by invert
      microscope, Giemsa staining and MTT assay. RESULTS: The results of
      immunocytochemistry showed that after Raji cells were treated by the injection of
      Prunella vulgaris L. (50 mg/ml) for 48 hours, the expression of bcl-1 was up
      regulated, and the expression of bax was down-regulated. The differences between
      process group and control group were significant (P < 0.01). CONCLUSION: Prunella
      vulgaris L. can suppress the proliferation of Raji cells and may be a new anti
      lymphoma drug. Inducing the apoptosis of Raji cells maybe one of anti-lymphoma
      mechanisms.

PMID- 17228665
TI  - [A pharmacology study of Cyclovirobuxinum D on curing myocardial ischemia induced
      by isoprenaline].
AB  - OBJECTIVE: To explore the pharmacology actions of Cyclovirobuxinum D (Cvb-D) for
      the myocardial ischemia and study its possible mechanism. METHODS: The rats were
      given orally with Cvb-D 0.55 g/kg, 1.1 g/kg and 2.2 g/kg per day, for 21 days.
      The myocardial ischemia model were induced by isoprenaline. The rats ECG, serum
      CPK, LDH, FFA and myocardium tissue SOD, MDA level were detected. RESULTS: Cvb-D
      could significantly reduce myocardial ischemia model induced by isoprenaline
      rats' sigmaJ of ECG, shorten ECG resume time, reduce serum FFA content, serum
      CPK, LDH activation, reduce cardiac tissue MDA content, raise the cardiac tissue
      SOD activation. CONCLUSION: Cvb-D can decrease the release of FFA, CPK, LDH and
      improve the model rats' myocardium MDA, SOD level. It may be some of mechanisms
      of its anti-myocardial ischemia effect.

PMID- 17228666
TI  - [Study on the use of ultrasound technique in extraction of polysaccharides from
      Loquat leaf].
AB  - In order to gain the optimal extract condition of extraction polysaccharides in
      Loquate leaf by ultrasound technique, the single factor and the orthogonal
      experiments were carried. The results showed that the optimal condition turned
      out to be ultrasound extraction time 35 min, ultrasound power 120W, extraction
      temperature 60 degrees C and the liquid-to-solid ratio 12: 1. In contrast to
      conventional extraction method, the ultrasound technique could be a better method
      for extracting the polysaccharides from Loquat leaf with a higher yield and
      shorter time.

PMID- 17228667
TI  - [Determination of acacetin in Xiangjuganmao Keli (no sweet) by HPLC].
AB  - OBJECTIVE: To establish a method for the determination of acacetin in
      Xiangjuganmao Keli (no sweet). METHODS: Acacetin in powdered herb was extracted
      by ultrasonator with methanol and was hydrolyzed with hydrochloric acid.
      Separation was accomplished on an ODS reversed phase column (5 microm, 4.6 x 250
      mm) with a mobile phase of methanol-water-acetic acid(350: 150: 2). The detective
      wavelength was at 340 nm. RESULTS: The method was accurate, the results were
      stable and reproducible. The linear range of calibration cure was within the
      concentration of 2.00 - 10.00 microg/ml (r = 0.9998). The average extraction
      recovery was 99.9% (n = 6), RSD = 0.41% (n = 6). CONCLUSION: The method is
      simple, convenient, sensitive, and reproducible for quality control of
      Xiangjuganmao Keli (no sweet).

PMID- 17228668
TI  - [Study on the preparation and quality standard of Ephedra sinica dispensing
      granules].
AB  - OBJECTIVE: To optimize the preparation process and to set up the quality standard
      of Ephedra sinica Dispensing Granules. METHODS: Nine experiments were carried out
      by L9 (3(4)) orthogonal design. Ephedra sinica Dispensing Granules was identified
      by TLC and the content of ephedrine was determined by HPLC. RESULTS: The optimal
      extraction process was as follows: the water that 10 times of Ephedra sinica, was
      decocted 3 times and each time was sustained for 1.5 hours. The linear
      relationship of ephedrine hydrochloride was at the range of 0.0081 - 0.1377
      microg (r = 0.999 9). The average recovery was 100.25% ( RSD = 2.24%, n = 6).
      CONCLUSION: The extraction process is scientific. The method is available with a
      good reproducibility and can control the quality of Ephedra sinica Dispensing
      Granules.

PMID- 17228669
TI  - [Study on the extraction process for salidroside and p-tyrosol in Rhodiola
      crenulata].
AB  - OBJECTIVE: To investigate the optimum ethanol extraction process conditions for
      salidroside and p-tyrosol from Rhodiola crenulata. METHODS: The extraction rate
      of ethanol extract and content of salidroside and p-tyrosol were chosen as the
      assessment index by using the orthogonal design. The ethanol content (%), solvent
      quantum (fold) and extracting time (hour) were reviewed. RESULTS: The optimum
      ethanol extraction process conditions were as follows: adding 6 fold of 80%
      ethanol, extracting for 2h and 2 times. CONCLUSION: The optimum extraction
      process can give a reference to the research of new medicine and production of
      industry.

PMID- 17228671
TI  - [Application of one-stage arteriovenous shunt to circulation reconstruction for
      extensive arterial ischemic disease of lower extremities].
AB  - OBJECTIVE: To investigate the clinical effect of the one-stage arteriovenous
      shunt on the extensive arterial ischemic disease of the lower extremities.
      METHODS: The one-stage arteriovenous shunts in the lower extremities were applied
      to 90 patients with extensive arterial ischemic diseases, including arterial
      occlusive disease (AODs, 62 patients) and thromboangiitis obliterans (TAOs,28
      patients). By the retrospective analysis on the clinical materials and the follow
      up of the postoperative patients, the immediate and the long-term surgical
      outcomes were summarized. RESULTS: During the hospitalization, 88 patients
      achieved a remarkable surgical effectiveness, with an immediate surgical
      effectiveness rate of 97.7% (88/90), but 2 patients failed in the operation and
      had to undergo amputation of the lower limb. Of the 72 patients who were followed
      up for 0.5-5 years after the arteriovenous shunt operation, 64 could have a
      sufficient blood supply to the lower extremities, with a long-term effectiveness
      rate of 88.9% (64/72); however, 8 patients had to undergo transplantation of the
      greater omentum or amputation of the lower limb. CONCLUSION: The one-stage
      arteriovenous shunt performed on the lower extremities for an extensive arterial
      ischemic disease is a simpler and more effective surgical protocol for
      reconstruction of the circulation of the patient who is not suitable for the
      operation of arterial bypass.

PMID- 17228672
TI  - [Intraoperative imaging to monitor prosthetic fixation for total hip
      arthroplasty].
AB  - OBJECTIVE: To explore the intraoperative imaging to monitor the prosthetic
      fixation for the total hip arthroplasty (THA) and to increase the accuracy of the
      primary THA prosthetic fixation. METHODS: From April 2000 to August 2005, 69
      patients (75 hips) underwent THA monitored by the imaging (the imaged THA group,
      Group I), and 72 patients (78 hips) underwent THA with the standard method (the
      standard THA group, Group S). There were 32 72 patients (78 hips) underwent THA
      with the standard method (the standard THA group s in Group S). There were 32
      males and 37 females in Group S. The mean ages of the patients in Group I and
      Group S were 62. 3 years and 60. 5 years respectively, ranging 46-75 years in
      Group I and 43-75 years in Group S. Preoperative diagnoses were femoral neck
      fractal measure (Garden III, IV ) in 23 patients (23 hips) in Group and 2 5
      patients (25 hips) in Group S, acetabular dysplasia Campbell I , II) in 9
      patients (10 hips) in Group I and 11 patients (13 hips) in Group S osteoarthritis
      in 16 patients (17 hips) in Group I and 15 patients (15 hips) in Group S, femoral
      head osteonecrosis (Ficat III, IV ) 15 patients (16 hips) in Group I and 17
      patients (17 hips) in Group S, and rheumatoid arthritis in 6 patients (9 hips) in
      Group I and 4 patients (8 hips) in Group S. There were 21 hips of cement
      prostheses in Group I and 22 hips in Group ferative 12 hips of cementless
      prostheses in Group I and 11 hips in Group S, 42 hips of cement and cementless
      prostheses in Group I and 45 hips in Group S. Group I used the standard THA and
      the intraoperative X-ray monitoring the prosthetic fixation in the numerical
      measure of abduction angle, anteversion angle, femoral neck length, and femoral
      offset distance. The items compared between Group I and Group S included
      incisional length, intraoperative bleeding, transfusion, operative time,
      frequency of X-ray imaging, infection, postoperative functional recovery, and
      prosthetic position of postoperative X-ray imaging. RESULTS The follow-up on 62
      patients in Group I and 64 patients in Group S for 6-64 months averaged 42 months
      revealed that there were statistically significant differences in incisional
      length, intraoperative bleeding. transfusion, operative time, frequency of X-ray
      imaging, postoperative functional recovery, prosthetic position of postoperative
      X-ray imaging, and the Harris score between Group I and Group S one year after
      operation. The results of Group I were significatnly better than those of Group
      S. CONCLUSION: The intraoperative X-ray imaging can increase the accuracy of the
      THA prosthetic fixation and reduce the incidence of THA maloperation by The X-ray
      imaging can also be used in county hospitals if C-arm fluoroscopy can be
      provided.

PMID- 17228670
TI  - [Effects of immunosuppressants on cytokine expressions after repair for nerve
      injury in a rat model].
AB  - OBJECTIVE: To explore effects of several immunosuppressants on cytokine
      expressions after repair for a sciatic nerve injury in a rat model. METHODS: The
      sciatic nerves of 42 rats were cut and sutured end-to-end. After operation, the
      rats were divided into 6 groups. Group A (n = 9) was served as a control with no
      medicines given. Group B (n= 9) was given methylprednisolone 20 mg/(kg x d) for 2
      days. Groups C(n= 9) and D(n = 3) were given FK506 1 mg/(kg - d) for 2 weeks and
      4 weeks respectively, and were given the same doses of methylprednisolone as
      Group B. Groups E and F were given CsA 2 mg/(kg - d) for 2 weeks and 4 weeks
      respectively, and were given the same doses of methylprednisolone as Group B. The
      sciatic nerves were sampled at 1, 2 and 4 weeks postoperatively. And
      immunohistochemistry stainings of interleukin 1beta (IL-1beta), tumor necrosis
      factor alpha (TNF-alpha), interferon gamma(IFN-gamma) and macrophage migration
      inhibitory factor(MIF) were performed. The staining results were compared and
      analyzed. RESULTS: The expression peaks of IL-1beta and IFN-gamma were found at
      the 1st week postoperatively in Group A. Then, the expression decreased rapidly
      at the 2nd week and disappeared at the 4th week. As for TNF-a and MIF, they were
      only found to have a low expression until the 1st week in Group A. In groups C-F,
      the expression peaks of IL-1beta, TNF-alpha and IFN-gamma were found at the 2nd
      week, while the expression peak of MIF was still at the 1st week, and the
      expression of all the cytokines extended to the 4th week. The expressions of
      these cytokines in Group B were just between the expression levels of Group A and
      Groups C-F. CONCLUSION: Immunosuppressants can delay the expression peaks and
      significantly extend the expression time of IL-1beta, TNF-alpha, IFN-gamma and
      MIF after repair for a sciatic nerve injury in a rat model.

PMID- 17228673
TI  - [An experimental study on prevention of peridural adhesion after laminectomy].
AB  - OBJECTIVE: To explore effective substances and methods for prevention of
      peridural adhesion. METHODS: Laminectomy was performed on the 5th lumbar segment
      in 64 rabbits, which were equally divided into 4 groups. The dura mater (12 mm x
      6 mm) was exposed. The exposed dura mater was left uncovered in Group A; the
      exposed dura mater was covered with sodium hyaluronate jel (high molecular
      weight, 1 ml) in Group B; the lamina repair was performed with the autologous
      spinous process in Group C; the lamina repair was performed with the sodium
      hyaluronate jel filling and the autologous spinous process in Group D. The
      specimens were observed grossly and histologically at 2, 4, 6 and 8 weeks
      postoperatively. The computed imaging analysis on the epidural adhesion was also
      performed at 6 weeks postoperatively. RESULTS: 1) The gross anatomical
      evaluation: Severe peridural adhesion was formed in Group A, less adhesion formed
      in Groups B and C, but no obvious adhesion formed in Group D. 2) The area
      percentage of the epidural scar: The area percentage of the epidural scar was
      15.89%+/-1.88% and 13.94%+/-1.89% in Groups C and D respectively, which were
      significantly lower than those in Groups A and B (22.66%+/-2.89% and 20.70%+/
      2.82%, P<0. 05). 3) The density of epidural scar: The density of the epidural
      scars were 42.03%+/-7.36% and 36. 50+/-9.08% in Groups B and D, which were
      significantly lower than those in Groups A and C (63.73%+/-6.06% and 52. 11%+/-
      4.10%, P< 0.05). CONCLUSION: The high molecular weight sodium hyaluronate jel
      filling combined with the lamina repair using the autologous spinous process has
      the best preventive effect on the peridural adhesion after laminectomy.

PMID- 17228674
TI  - [Determination on contents of matrix metalloproteinase 3 and interleukin 1 in
      tissues of lumbar disc herniation and their roles in pathogenesis].
AB  - OBJECTIVE: To determine the contents of matrix metalloproteinase 3 (MMP-3) and
      interleukin 1 (IL-1) in the tissues of the lumbar disc herniation and to
      investigate their roles in the pathogenesis. METHODS: The tissues of the
      herniated lumbar disc were obtained from 30 patients undergoing surgery for
      persistent radiculopathy from June 2003 to December 2004 and at the same time
      these samples were divided into the following three experimental groups: the
      bulge group (n =11), the protrusion group (n = 9), and the prolapsus group (n =
      10), 14 males, 16 females, aged 33-64 years. As the control group, 9 lumbar disc
      specimens were harvested from 9 patients (4 males, 5 females, aged 21-58 years)
      suffering from bursting fracture of the lumbar spine. The specimens were analyzed
      by the ELISA method for the contents of MMP-3 and IL-1. RESULTS: The contents of
      MMP-3(14.25+/-1. 32, 19.89+/-2.97, 20.69+/-2.18 ng/ml in the bulge group,
      protrusion group and prolapsus group, separately) and IL-1 (8.52+/-0.22, 11.88+/
      0.52, 11.90+/-0.73 pg/ml in the bulge group, protrusion group and prolapsus
      group, separately) in the experimental groups were significantly higher than
      those in the control group. The contents of MMP-3 and IL-1 in the protrusion
      group were not significantly higher than those in the prolapsus group, but they
      were significantly higher than those in the bulge group(P<0.01). The contents of
      MMP-3 had a significant relationship with the contents of IL-1 in the three
      experimental groups and the control group(P<0. 01). CONCLUSION: The result
      demonstrates that the tissues of the lumbar disc herniation can produce both MMP
      3 and IL-1, which may have an unknown but important relationship with each other.

PMID- 17228676
TI  - [Reconstruction of nasal subunits with reversed vascularized preauricular and ear
      composite flap].
AB  - OBJECTIVE: To explore the technique for reconstructing nasal subunits with the
      reversed vascularized preauricular and ear composite flap. METHODS: From June
      2003 to August 2005 the preauricular and ear composite flap, which was pedicled
      by the reversed superficial temporal vessel, was harvested and transplanted to
      repair the defects of the nasal tip, soft triangle, and ala by the microsurgical
      technique. The flap ranged in area from 3.5 cm x 2. 5 cm to 2. 0 cm x 1. 5 cm,
      with the pedicles 4 to 6 cm in length. The reversed superficial temporal vessel
      pedicles were directly anastomosed to the angular artery and vein adjacent to the
      nasal ala. RESULTS: Among the 12 patients who had been treated, 11 had their
      vessel pedicles successfully anastomosed to the angular vessels, while the
      remaining 1 patient had the stump of the superficial temporal vessel anastomosed
      after the flap harvest via the vessel graft because the angular vessels were not
      found in the recipient area. All the flaps survived with a satisfactory esthetic
      result after operation. CONCLUSION: The technique for reconstructing nasal
      subunits with the reversed vascularized preauricular and ear composite flap,
      which is directly anastomosed to the angular vessel, can avoid the vessel
      grafting and therefore it can avoid an additional damage to the patient.

PMID- 17228675
TI  - [Submental island flaps for reconstruction of hypopharyngeal non-circumferential
      defects after hypopharyngeal carcinoma removal].
AB  - OBJECTIVE: To study the feasibility, surgical techniques, and results of
      submental island flaps for reconstruction of hypopharyngeal non-circumferential
      defects. METHODS: A retrospective review of the archives was performed on 16
      patients (6 males, 10 females, aged 41-78 years) who suffered from hypopharyngeal
      cancer. From August 1998 to August 2002, the patients underwent a partial removal
      of the hypopharynx and reconstruction by submental island flaps. Their
      hypopharyngeal carcinomas belonged to squamous carcinoma. Of the 16 patients (2
      in UICC clinical stage I , 11 in m , 3 in IV ), 9 had their pathological origin
      in the pyriform sinus, 4 in the posterior pharyngeal wall, and 3 in the
      postcricoid. The flap area ranged from 8. 0 cm x 4. 5 cm to 5. 0 cm x 3. 0 cm.
      RESULTS: The follow-up for 3-7 years showed that the submental island flaps
      healed well in all patients with a success rate of 100%. The swallowing function
      returned to normal 10-14 days after operation without complications of salivary
      fistula and infection. The 3-year and 5-year survival rates were 68. 8% (11/16)
      and 62. 5% (5/8), respectively. CONCLUSION: Submental island flaps are convenient
      for reconstruction of hypopharyngeal non-circumferential defects, and they are
      safe and reliable, too.

PMID- 17228677
TI  - [Synthetical treatment for facial paralysis using static and dynamic techniques].
AB  - OBJECTIVE: To investigate a synthetical technique combining static and dynamic
      states for treating facial paralysis. METHODS: From October 1993 to November
      2005, 93 patients (26 males, 67 females; aged 9-69 years; illness course, 6
      months to 24 years) with facial paralysis were admitted for treatment, of whom 48
      were unknown in their pathological origins, 32 had a history of intracranial or
      ear operation, 13 had their facial paralysis related to trauma. We applied
      synthetical techniques for treating facial paralysis, including denerved muscle
      (extensor hallucis brevis and extensor digitorum brevis) free graft using an
      operating or chemical technique, temporal muscular flap suspending, treatment of
      eye closure by uplifting zygomo-malar tissues and temporal muscular flap
      suspending, brow lifting by the Buried Guiding Suture Appliance, Botox injection,
      and the nerve amputation of normal side for mandibular marginal ramus paralysis.
      RESULTS: After the treatment for 82 patients with the method of the denerved
      muscle free graft combining femoral muscular flap suspending, 3 patients with the
      method of uplifting zygomo-malar tissues combining temporal muscular flap
      suspending for eye closure, 15 patients with the method of the Buried Guiding
      Suture for eyebrow lifting, 4 patients with the Botox injection and nerve
      amputation of normal side for the mandibular marginal ramus paralysis, 93
      patients had a good therapeutic result. The follow-up for 3 months to 10 years in
      all the patients revealed that 75 patients were satisfied with their treatment
      results and 13 patients were almost satisfied according to the criteria for the
      facial symmetrical checking and the House-Brackmann grading system. The technique
      had advantages of a complete survival of the related small muscles, a hidden
      incision, less trauma for the Botox injection, and the denerved muscles for
      surrounding nerve inserting. CONCLUSION: The synthetical technique combining
      static and dynamic states for treating facial paralysis is a good therapeutic
      method and the therapies for facial paralysis should vary with the different
      conditions of the paralysis. We advocate an individuation treatment for facial
      paralysis.

PMID- 17228678
TI  - [Prevention and treatment of postoperative complications after skin soft tissue
      expansion for scar alopecia].
AB  - OBJECTIVE: To summarize the prevention and treatment of postoperative
      complications after the skin soft tissue expansion for scar alopecia. METHODS:
      From January 1995 to June 2005, 57 patients with scar alopecia were admitted to
      our department for treatment. Of the patients, 25 were males and 32 were females
      with their ages ranging from 5 to 55 years. The causes were burn in 33 patients,
      trauma in 14, alopecia after head surgery in 8, and other causes in 2. Their
      disease courses ranged from 6 months to 15 years. For treatment, 89 therapeutic
      expanders were utilized in 57 patients. The retrospective analysis on the
      complications and their prevention and treatment were performed. RESULTS: The
      follow-up for 3-12 months averaged 6 months revealed that 81 areas undergoing the
      expander insertion healed well and the hair grew well, too. Eight areas
      undergoing the expander insertions had complications, including expander exposure
      in 2 patients, infection in 2, hematoma in 1, expander rupture in 1, necrosis of
      the flap tip in I, and scar necrosis at the injection port in 1. The results also
      revealed that there was a significantly increased rate of complications in the
      patients aged 5-10 years and the patients older than 50 years (P<0. 05). The
      complication rate in the patients who received 2 expanders at one time was
      significantly higher than that in the patients who received only 1 expander (P<0.
      05). However, there was no significant difference in the complication rate in the
      other kinds of patients. All the complications were effectively treated with a
      satisfactory therapeutic result. CONCLUSION: The skin soft tissue expansion for
      scar alopecia can effectively prevent and treat postoperative complications. If
      the complications are identified early and treated properly, the therapeutic
      results will be satisfactory.

PMID- 17228679
TI  - [Classification of finger flaps and its use in emergency treatment for finger
      injuries].
AB  - OBJECTIVE: To choose the homo-digital and the hetero-digital flaps in the
      reconstruction of the distal finger injuries and to summarize the treatment
      results obtained in the clinical practice. METHODS: From August 2001 to June
      2005, 112 injured fingers in 108 patients (68 males, 40 females; aged 16-63
      years) were surgically treated. The injuries were due to emotion, crushing or
      avulsion, and they underwent operations 2 hours after the injuries. Nine kinds of
      flaps were taken from the dorsal or volar aspect of the injured fingers to cover
      the defects of the distal fingers. The flaps were divided into two kinds: 1) The
      flaps were nourished by the main digital arterial branches, including the V-Y
      island flap based on the digital neurovascular bundles, the reversed digital
      artery flap, the modified Moberg flap, and the twins flaps based on the digital
      general neurovascular bundles (flaps ranging in area from 1.5 cm X 2.00cm); and r
      The flaps were nourished by the collateral digital arterial branches, including
      the dorsoulnar arterial retrograde flap of the thumb(flaps ranging in area from
      1. cm X 1.. cm to 3.. cm Xx2. 5 cm) and the reverse flap based on the dorsal
      branches of the digital artery (flaps ranging in area from 1. 7 cmX x1. 0 cm to
      4. 5 cmX x . 0 cm), the volar flap based on the transverse palmar branch of the
      digital artery (flaps ranging in area from 2.0 cm Xx1.0 cm to 2. 5 cm Xx2. 0 cm).
      and the island flap from the dorsum of the index finger and the digital local
      flaps. RESULTS: The follow-up for 2 weeks to 8 months revealed that all the flaps
      survived with an exception of flap necrosis in 3 patients and superficial
      necrosis in 3 patients. The sensation reached almost normal levels in the flaps
      based on collateral digital arteries and the two-point discrimination was between
      5 mm and 10 mm in the flaps based on the arterial branches. The finger motion
      ability was good and the finger appearance was satisfactory. CONCLUSION: The
      choice of the above-mentioned skin flaps can repair the soft tissue defects of
      the distal parts of the fingers, which can have a satisfactory restoration
      contour.

PMID- 17228680
TI  - [Application of pedicled anterolateral thigh flap transferring for coverage of
      oversized skin defect of hand].
AB  - OBJECTIVE: To introduce the application of the pedicled anterolateral thigh flap
      transferring for coverage of the oversized skin defect of the hand. METHODS: The
      pedicled anterolateral thigh flap was transferred to cover the large skin defects
      of the hands or the skin defects of the abdomen after the abdominal flap
      transferred to the hand in 5 male patients aged 16-44 years from April 2002 to
      August 2005. The injured sites were as follows:4 right hands and 1 left hand,
      including 2 hands injured by a machine and 3 hands injured by burning. The
      mechanically injured patients underwent an operation within 6 hours after the
      injury. The burned patients were reconstructed by the flap transferring 4-7 days
      after the burn when the decayed tissues could be clearly indentified. The areas
      of the hand defects were 12-19 cm x 18-22 cm. The areas of the pedicled
      anterolateral thigh flaps were 7-12 cm x 16-24 cm. The areas of the abdominal
      flaps were 13-20 cm x 19-23 cm. The pedicles were separated 3 weeks after the
      repairing operation. RESULTS: All the flaps survived well and there was no
      vascular crisis, with the wound healing of the first intention. The skin defects
      of the hand were covered completely. Five patients were followed up for 6-12
      months. The texture of the flaps was soft and the flaps had a good blood
      circulation. Of the patients, 3 underwent the finger exclusion and degreasing
      operation 4-7 months after operation. All the flaps of the hands had protective
      sensation, which could meet the requirement of the daily life. CONCLUSION: The
      pedicled anterolateral thigh flap can provide the large coverage for the skin
      defects of the hands. The risk of the operation can be greatly decreased by
      obviation of the vessel anastomosis. It can be an optimal choice for the
      management of the oversized skin defects of the hands.

PMID- 17228681
TI  - [Comparison between two different repairing methods for skin defects of foot and
      ankle].
AB  - OBJECTIVE: To explore a suitable repairing method for skin defects of the foot
      and ankle, and to evaluate the therapeutic effects of the different repairing
      methods. METHODS: From January 2000 to October 2005, 36 patients with skin
      defects of the foot and ankle underwent the repairing treatment, of whom 35 were
      males and 1 was patients with skin defects of the foot and ankle underwent the
      repairing treatment, of whom 35 were males and 1 was 2 repaired groups. And the
      patients in the 2 groups were equally satisfied with the repairing treatments.
      female, aged 5-62 years, averaged 38 years. Of the 36 patients, 12 had an injury
      by a machine, 22 had a traffic accident, 1 had an infection, and 1 had a cold
      injury. And the injuries involved the dorsum of the foot, heel, forefoot, and
      medial or lateral malleolus. The injuries were respectively treated by 2
      different repairing methods, the repair with the coverage by the lateral
      supramalleolar flaps and the repair with the coverage by the reverse sural
      neurocutaneous flaps. The skin defects ranged in area from 5 cm x 4 cm to 20 cm x
      10 cm. The lateral supramalleolar flap was used in 15 patients (15 flaps) with a
      flap area of 5 cm x 4 cm-15 cm x 8 cm, and the reverse sural neurocutaneous flap
      was used in 21 patients (22 flaps) with a flap area of 6 cm x 4 cm-20 cm x 10 cm.
      We retrospectively observed the therapeutic results and compared the success
      rates of the two methods. RESULTS: Of the 36 patients, 15 underwent the repair
      with the coverage by 15 lateral supramalleolar flaps; 10 achieved a complete
      survival of the flaps, 2 developed an epidermal necrosis over the distal part,
      and 3 developed a complete necrosis. The other 21 patients underwent the repair
      with the coverage by 22 reverse sural neurocutaneous flaps. Of the 22 flaps, 21
      had a complete survival, and only 1 failed to coverage by 22 reverse sural
      neurocutaneous flaps. Of the 22 flaps, 21 had a complete survival, and only 1
      failed to survive. The comparison revealed that there was no difference in the
      color, texture, and contour of the flaps between the 2 repaired groups. And the
      patients in the 2 groups were equally satisfied with the repairing treatments.
      The sensation of the flaps recovered to S0-S1. CONCLUSION: The repairing of the
      foot and ankle skin defects with the coverage by the lateral supramalleolar flaps
      or by the reverse sural neurocutaneous flaps can achieve a similar good
      therapeutic result. However, the repair with the lateral supramalleolar flaps is
      more suitable for the skin defect of a smaller area over the medial or lateral
      malleolus, or the proximal dorsum of the foot; the repair with the reverse sural
      neurocutaneous flaps is more suitable for the skin defect of a larger area over
      the foot and ankle without serious destruction of the malleolar arterial rete.

PMID- 17228682
TI  - [Repair of extensive gluteal-sacral defect with posterior femoral cutaneous
      neurovascular island flap].
AB  - OBJECTIVE: To explore the clinical value of repairing extensive gluteal-sacral
      defects with the posterior femoral cutaneous neurovascular island flap. METHODS:
      From July 2002 to May 2005, the posterior femoral cutaneous neurovascular flap
      was applied to repairing extensive gluteal-sacral defects in 6 patients (3 males,
      3 females; aged 31-59 years). Three patients had a skin defect in the gluteal
      sacral region caused by squamous cell carcinoma, 1 patient had the defect in the
      same region caused by malignant fibrohistiocytoma, and 2 patients had the defect
      caused by bedsores of grade III . The area of defects ranged from 15 cm X 8 cm to
      16 cm X 10 cm. The flaps ranged in area from 15 cm x 8 cm to 18 cm x 10 cm.
      RESULTS: In all the 6 patients had their flaps survived well and the wounds
      gained the primary healing. The follow-up for 2. 5-12 months revealed that, flaps
      were satisfactory in their appearance, texture, and sensory functions.
      CONCLUSION: The repair of extensive gluteal-sacral defects with the posterior
      femoral cutaneous neurovascular island flap has advantages of the unchanged
      anatomic structures, reliable blood supply, easy dissection for extensive
      defects, good sensory recovery, and sacrificing no major vessels; therefore, this
      kind of repair is an optimal approach to repairing extensive gluteal-sacral
      defects.

PMID- 17228683
TI  - [Distal perforator-based gluteus maximus muscle V-Y flap for treatment of sacral
      ulcers].
AB  - OBJECTIVE: To explore the method of the distal perforator-based gluteus maximus
      muscle V-Y flap to treat the sacral ulcer and to simplify the operative
      procedures. METHODS: From March 2002 to March 2005, 11 cases of sacral ulcer were
      repaired by distal perforator-based gluteus maximus muscle flaps. The area of
      sacral ulcer ranged from 13 cmX 11 cm to 18 cmX 14 cm. Of 11 cases, 7 were female
      and 4 were male, whose age ranged from 21 to 69 years, and the disease course was
      8 months to 3 years. A triangular flap was designed to create a V-Y advancement
      flap. The length of the base was made almost equal to the diameter of the defect.
      The apex of the triangle was located near the great trochanter. The medial part
      of the flap was elevated as a fasciocutaneous flap by dissecting the layer
      between the fascia and the muscle. The distal part of the flap was elevated by
      dissecting the layer between the gluteus maximus muscle and the fascia of the
      deeper muscle group. The flap was advanced to the defect. RESULTS: All the flaps
      survived. After a follow-up of 5 months to 3 years, the bilateral buttocks were
      symmetry and whose appearance was satisfactory. Except for 1 case dying of other
      disease, no recurrence of ulcer was observed. All the flaps survived. CONCLUSION:
      The distal perforator-based fasciocutaneous V-Y flap for treatment of sacral
      ulcers is a simple and reliable technique, which has several advantages over the
      conventional V-Y flap technique,such as excellent excursion, viable coverage.with
      the fasciocutaneous component, high flap reliability, preservation of the
      contralateral buttock, and preservation of the gluteus maximus muscle function.

PMID- 17228684
TI  - [Clinical studies on maintenance of cross-leg position through internal fixation
      with Kirschner wire after cross-leg flap procedure].
AB  - OBJECTIVE: To study the feasibility of a new method for the cross-leg position
      maintained by the Kirschner wire internal fixation after the cross-leg flap
      procedure. METHODS: From December 2004 to October 2005, 5 patients (4 males, 1
      female; aged 14-52 years) were admitted to our department, who suffered from the
      tibia exposure or the internal fixation plate exposure after operation because of
      the tibia fracture by trauma for 1-8 weeks. The soft tissue defects ranged in
      area from 2.4 cm x 2.0 cm to 4. 2 cm x 3.0 cm. The soft tissue around the wound
      in the leg was too poor in condition to perform an operation of the local flap
      transplantation, but the wound and the tibia had no obvious infection, so an
      operation of the cross-leg flap transplantation was performed to cover the
      wounds. The operation was performed with the routine cross-leg flap method
      introduced in the medical literature. After operation the cross-leg position was
      maintained through a simple internal fixation with two Kirschner wire, which were
      inserted through the tibia of the cross region of both the legs, and layers of
      dressings were placed as a cushion between the crossed legs in case of the
      crushing skin ulcer formation. The effect of fixation, blood circulation in the
      cutaneous flap, and the stress of the pedicle were observed postoperatively.
      After 3-4 weeks the pedicle of the cross-leg flap was cut off; the crossed legs
      were detached and the Kirschner wire were pulled out. RESULTS: All the flaps
      survived with a good blood circulation and a low pedicle stress. The patients had
      a relatively comfortable position because all the areas of the legs could be
      allowed to make some motions except the cross-area of the legs. Another advantage
      of this fixation method was its convenience for observing the blood circulation
      of the cutaneous flap and for changing the dressings. Neither infection in the
      holes of the Kirschner wire nor crushing skin ulcer formation in the area of the
      cross-leg could be observed. The follow-up for 3-18 months revealed that all the
      flaps were in good condition with no edema, contracture or skin pigmentation.
      CONCLUSION: The method of using the Kirschner wire to maintain the cross-leg
      position after the cross-leg flap procedure has more advantages than the plaster
      fixation. This improved method is simpler, and can achieve a tighter fixation in
      the cross-leg area to maintain the cross-leg position, allowing a micro-motion in
      other parts of the legs. The patients can have a relatively comfortable posture,
      and have a more convenient dressing changes and observation on the blood
      circulation in the flaps.

PMID- 17228685
TI  - [Internal fixation for pelvic posterior ring lesions].
AB  - OBJECTIVE: To explore the choice for the internal fixation in treatment of pelvic
      posterior lesions. METHODS: From May 2000 to June 2005, the treatment was given
      to 40 patients (28 males, 12 females, aged 21-58 years) with pelvic posterior
      ring fracture and dislocation. Of the patients, 23 had a traffic accident, 11 had
      a crush injury and 6 had a fall. As for the state of an injury to the pelvic
      posterior ring, 22 patients had dislocation of the sacroiliac joint, 12 had a
      sacrum fracture dislocation, and 6 had an ala iliac fracture and dislocation of
      the sacroiliac joint. According to the Denis (1988) classification, fracture of
      the (sacral region I was found in 6 cases, fracture of the sacral) region II in 3
      cases, and fracture of the sacral region III in 3 cases. As for the complication
      of the pelvic front ring fracture: separation of the symphysis pubis was found in
      14 cases, fracture of the superior ramus and inferior ramus of the pubis on one
      side in 10 cases. The two-side superior ramus of public and inferior ramus of
      pubis in 8 cases, homopleural acetabular fracture on one side in 4 cases,
      acetabular fracture on one side and contralateral superior ramus and inferior
      ramus fracture of the pubis in 3 cases, and acetabular fracture on the opposite
      side in 1 case. As for the operation, 28 patients underwent the still-plate
      internal fixation of the sacroiliac joint from anterior at 24 h to 15 days after
      the injury, 2 underwent the screw internal fixation of the sacroiliac joint from
      posterior, and remaining 10 underwent the internal fixation by the Galveston
      Technique associated with the ISOLA system. The therapeutic results were
      analyzed. RESULTS: The follow-up of the 40 patients for 6 months to 3 years
      revealed that before operation 3 had a sacral plexus nerve injury, and after
      operation 1 patient developed perineum numbness and urinary incontinence, 1
      developed claudication,3 developed posterior urethral fragmentation, and 2
      developed urinary bladder rupture; however, they had a complete recovery after
      the reparative surgery. CONCLUSION: In treatment of the pelvic posterior ring
      lesions, an appropriate internal fixation can be chosen according to the type of
      the pelvic fracture, applicability of internal fixation, condition of the
      patient,equipment available, and the doctor's experience.

PMID- 17228686
TI  - [Reparative treatment of urethral defect in adult penis].
AB  - OBJECTIVE: To summarize the methods of repairing the urethral defect in the penis
      of an adult and the clinical application of the island skin flaps of the scrotum
      septum to the reparative treatment. METHODS: From January 2000 to November 2005,
      twenty-six cases of urethral defect in penis, including 16 cases of congenital
      urethral defect, 6 cases of traumatic urethral defect in middle penis, and 4
      cases of distal urethral defect, were repaired by the local penis fascia flaps.
      The island skin flaps of the scrotum septum were transferred to cover the penis
      wound. The pedicle contained the artery of the posterior scrotum and the artery
      of the anterior scrotum. The flap taken from the scrotum septum was 2.5 cm x 5.5
      cm in area. RESULTS: After a follow-up of 7 months to 4 years, all the 26
      patients had the healing of the first intention without urethral fistula,
      urethral narrowness or penis curvature, except 4 patients who developed infection
      and leakage of urine, but the wounds healed spontaneously 2-4 weeks after
      operation. CONCLUSION: The penis fascia flaps and the island skin flaps of the
      scrotum septum can be used to repair the urethral defect in the penis of an
      adult. The blood supply to the flaps is sufficient and all the flaps can survive
      well. A good shape and function of the penis can be obtained.

PMID- 17228687
TI  - [Preliminary evaluation on seroma prevention and treatment with transposition of
      tissue flaps and arista hemostatic powder].
AB  - OBJECTIVE: To investigate and evaluate prevention and treatment of seroma by
      transposition of tissue flaps and Arista hemostatic powder after regional lymph
      node resection in patients with malignant tumors. METHODS: Twelve patients (6
      males, 6 females; aged 31-81 years, with metastatic tumors underwent prevention
      and treatment of seroma with the tissue flaps and Arista hemostatic powder spray
      after regional lymph node resection. The metastatic tumors involved the axilla in
      1 patient with breast carcinoma, the iliac and inguinal regions in 2 patients
      with carcinomas of the uterine cervix and the rectum, and the inguinal region in
      9 patients, including 4 patients with malignant fibrous histiocytoma(3 in the
      thigh, 1 in the leg), 2 patients with squamous carcinomas in the leg, 1 patient
      with synovial sarcoma in the knee, 1 patient with epithelioid sarcoma in the leg,
      and 1 patient with malignant melanoma in the foot. As for the lymph node removal
      therapy. 1 patient underwent axillary lymph node removal, 2 patients underwent
      lymph node removal in theiliac and inguinal regions, and 9 patients underwent
      lymph node removal in the inguinal region. Meanwhile, of the 12 patients, 6
      patients underwent transposition of sartorius flaps with Arista hemostatic
      powder, 3 patients underwent transposition of the rectus abdominis myocutaneous
      flaps (including 2 patients treated with Arista spray befor the wound closure and
      1 patient treated by transposition of local skin flaps with Arista spray used
      again),and 3 patients underwent only the suturing of the wounds combined with
      Arista. At the same time, of the 12 patients,only 4 patient underwent the
      transplantation of artificial blood vessels. RESULTS: The follow-up for 2-10
      months after operation revealed that 10 patients, who had received the
      transposition of tissue flaps and the spray of Arista hemostatic powder, had the
      first intention of the incision heal with seroma cured. Nine patients were given
      a preventive use of Arista hemostatic powder and therefore no seroma developed.
      The combined use of the transposition of tissue flaps and Arista hemostatic
      powder spray achieved a success rate of 100% in the prevention or treatment of
      seroma. However, 1 patient developed microcirculation disturbance 24 hours after
      operation and underwent disarticulation of the hip; 1 patient developed pelvic
      cavity hydrops and died 10 months after operation. CONCLUSION: The combined use
      of transposition of tissue flaps and Arista hemostatic powder spray can
      effectively prevent or treat seroma after regional lymph node removal in a
      patient with malignant tumor.

PMID- 17228688
TI  - [Construction of recombinant adenovirus bearing human transforming growth factor
      beta1 and bone morphogenetic protein 7 genes and its directional inducement
      effect on marrow stromal cells].
AB  - OBJECTIVE: To construct the recombinant adenovirus bearing human transforming
      growth factor beta1 (TGF-beta1) and bone morphogenetic protein 7 (BMP-7) genes,
      and investigate its co-expression in the marrow stromal stem cells (MSCs) and
      bioactivity effect. METHODS: Using the replication defective adenovirus AdEasy as
      a carrier, MSCs were infected by the high-titer-level infected recombinant
      adenovirus taking TGF-beta1 and BMP genes. Immunocytochemistry, in situ
      hybridization ,reverse transcription-polymerase chain reaction (RT-PCR), and
      hexuronic acid level test were used to detect the co-expression of the exogenous
      genes and to analyze their effect transfection on directive differentiation of
      MSCs. RESULTS: The immunocytochemistry staining showed that the brown coarse
      grains were situated in the cytoplasm of the most MSCs 72 h after infection.
      Procollagen I mRNA in the cells was detected by the in situ hybridization, and
      the content of hexuronic acid in the culture medium was significantly increased
      10 days after infection compared with the level before infection (P<0. 01).
      CONCLUSION: The recombinant adenovirus bearing human TGF-beeta1 and BMP-7 genes
      can be constructed, and the exogenous gene can be co-expressed in MSCs, which may
      offer a novel approach to the local combination gene therapy for repairing joint
      cartilage defects.

PMID- 17228689
TI  - [Articular cartilage defects repaired with homograft of mesenchymal stem cells
      seeded onto medical collagen membrane of guided tissue regeneration].
AB  - OBJECTIVE: To investigate the curative effects of homograft of the mesenchymal
      stem cells (MSCs) combined with the medical collagen membrane of the guided
      tissue regeneration(MCMG) on the full thickness defects of the articular
      cartilage. METHODS: MSCs derived from New Zealand rabbits aged 3-4 months
      weighing 2. 1-3.4 kg were cultured in vitro with a density of 5.5 x 10 (8)/ml and
      seeded onto MCMG. The MSC/MCMG complex was cultured for 48 h and transplanted
      into the full thickness defects on the in board condyle and trochlea. Twenty
      seven healthy New Zealand rabbits were randomly divided into 3 groups of 9
      rabbits in each. The cartilage defects in the in board condyle and trochlea were
      filled with the auto bone marrow MSCs and MCMG complex (MSCs/ MCMG) in Group A
      (Management A), with only MCMG in Group B (Management B) and with nothing in
      Group C (Management C). Three rabbits were killed at 4, 8 and 12 weeks after
      operation in each group, and the reparative tissue samples evaluated
      grossly,histologically and immunohistochemically were graded according to the
      gross and histological scale. RESULTS: Four weeks after transplantation, the
      cartilage and subchondral bone were regenerated in Group A; for 12 weeks, the
      regenerated cartilage gradually thicker; 12 week after transplantation, the
      defect was repaired and the structures of the articular surface and subchondral
      bone was.in integrity. The defects in Group A were repaired by the hyaline-like
      tissue and the defects in Groups B and C were repaired by the fibrous tissues.
      Glycosaminoglycan and type II collagen in Groups A, B and C were reduced
      gradually. The statistical analysis on the gross at 12 weeks and the histological
      gradings at 4 weeks, 8 weeks and 12 weeks showed that the in board condylar
      repair had no significant difference compared with the trochlearepair(P>0. 05).
      Management A was significantly better than Managements B and C (P<0. 05), and
      Management B was better than Management C (P<0. 05). CONCLUSION: Transplantation
      of the MSCs combined with MCMG on the full thickness defects of the articular
      cartilage is a promising approach to the the treatment of cartilage defects. MCMG
      can satisfy the demands of the scaffold for the tissue-engineered cartilage.

PMID- 17228690
TI  - [Experimental studies on tissue engineered esophagus reconstructed with
      artificial biodegradable scaffold].
AB  - OBJECTIVE: To verify adhesion and growth ability of canine esophageal epithelial
      cells (EECs) on the poly (lactic-co-glycolic acid) (PLGA), a three-dimensional
      biodegradable polymer scaffold, and to reconstruct the canine esophagus by the
      tissue engineering. METHODS: Free canine EECs isolated from adult dogs by
      esophagoscopy were seeded onto the PLGA scaffolds precoated with collagen type IV
      after the first passage by the in vitro culture. Then, the composites of the cell
      scaffold were respectively cultured in vitro and in the abdominal cavity of the
      dog in vivo. After different periods, the cell-seeded scaffolds were assessed by
      histological HE staining, scanning electron microscopy, and immunohistochemical
      analysis. RESULTS: The cells displayed a cobblestone-shaped morphology that was
      characteristic of the epithelial cells and were stained to be positive for
      cytokeratin, which indicated that the cells were EECs. The canine EECs were well
      distributed and adhered to the PLGA scaffolds, and maintained their
      characteristics throughout the culture period. After the culture in vivo for 4
      weeks, the cell-seeded scaffolds looked like tissues. CONCLUSION: PLGA scaffolds
      precoated with collagen type IV can be suitable for adhesion and proliferation of
      EECs, and can be used as a suitable tissue engineering carrier of an artificial
      esophagus.

PMID- 17228691
TI  - [Effects of WO-1 on repair of bone defects in rabbits].
AB  - OBJECTIVE: To evaluate the effect of WO-1 on repair of the bone defect in the New
      Zealand rabbit radius by an oral or local administration. METHODS: Bone defects
      were surgically created in the bilateral radii of 36 Zealand rabbits (1.6-2.0
      kg), which were randomly divided into 3 groups. In Group A, the defective areas
      were given WO-1 0.1 ml (50 mg/ml) by the local injections; in Group B, the
      rabbits were given WO-1 5 mg each day by the oral administration. Group C was
      used as a control group. Among each of the 3 groups, 4 rabbits were randomly
      selected and were sacrificed at 20, 30 and 60 days after operation, respectively.
      Then, the serological, X-ray and histological examinations were performed.
      RESULTS: The serum alkaline phosphatase and bone gla-protein levels were
      significantly higher at 20 and 30 days after operation in Groups A and B than in
      Group C, but significantly lower at 60 days after operation in Groups A and B
      than in Group C(P<0. 01). The X-ray and histological examinations at 20, 30 and
      60 days after operation revealed that the callus formation and remodeling were
      earlier in Groups A and B than in Group C, and the remodeling was earlier and
      better in Group A than in Group B. CONCLUSION: WO-1 can promote the repair of the
      radial defect in a rabbit; however, further studies on the dose-effect
      relationship, administration time, and administration route are still needed.

PMID- 17228692
TI  - [Separation and culture of human epidermal stem cells in vitro].
AB  - OBJECTIVE: To investigate the culture method for epidermal stem cells in vitro.
      METHODS: The epidermis was separated from the dermis, and shaken for 10 min in
      0.05% trypsin at 37 C to dissociate into single cells. Epidermal stem cells were
      selected by rapid attachment to collagen IV for 10-15 min and cultured on
      collagen IV or 3T3 feeder layer. All the cells were grown in DMEM without
      calcium, supplemented with 10% chelexed fetal bovine serum, 10 microg/L epidermal
      growth factor, 0.05 mmol/L CaCl2 and 0. 8 mg/L hydrocortisone. Cultures were
      observed for colony formation under a phase contrast microscope. The phenotypes
      of epidermal stem cells were detected by flow cytometry and immunocytochemistry
      staining. RESULTS: The cells selected by rapid adherence to collagen IV formed
      large colonies at 7- 8 days, expressed K19 antigen. The percentages of cells at
      the G0 and G1 phases of the cell cycle and the percentage of alpha 6 briCD71 dim
      cells in the experimental groups were higher than those in the control group. It
      indicated that there was a significant difference between the experimental groups
      and the control groups(P<0. 05). CONCLUSION: The human epidermal stem cells can
      be selected by rapid attachment to collagen IV, and they can be expanded in
      culture if the appropriate conditions are maintained.

PMID- 17228693
TI  - [Effects of bone marrow mesenchymal stem cells enriched by small intestinal
      submucosal films on cardiac function and compensatory circulation after
      myocardial infarction in goats].
AB  - OBJECTIVE: To investigate effects of the autologous bone mesenchymal stem cells
      (MSCs) enriched by the small intestinal submucosa (SIS) film implantation on the
      myocardial structure, cardiac function, and compensatory circulation after
      myocardial infarction in the goats. METHODS: Sixteen black goats were selected
      and divided randomly into the control group (n= 8)and the experimental group (n=
      8). The chronic myocardial infarction models were made by the ligation of the far
      end of the left anterior descending coronary artery. At the same time, MSCs were
      aspired from the thigh bone of the goats in the experimental group. MSCs were
      isolated by the centrifugation through a percoll step gradient and purified by
      the plating culture and depletion of the non-adherent cells. Primary MSCs were
      cultured in the DMEM medium supplemented with the fetal bovine serum in vitro.
      After that, the cultures were labeled by 5- BrdU. The active cells were
      transplanted into the SIS film. Six weeks after the ligation, the MSCs-SIS film
      was implanted by its being sutured onto the infarction area; whereas, the control
      group underwent a sham-operation. In both groups, echocardiographic measurements
      were performed before infarction, 6 weeks after infarction and 6 weeks after the
      MSC-collagen implantation, respectively, to assess the myocardial structure and
      cardiac function. The left coronary artery angiography was performed with the
      digital subtraction angiography. RESULTS: In an assessment of the left
      ventricular function, at 6 weeks after operation, the stroke volume and the
      ejection fraction of the control group and the experimental group were 42.81+/
      4.91, 37. 06+/-4.75 ml and 59.20%+/-5.41%, 44.56% +/-4.23%, respectively
      (P<0.05). The end-diastolic volume and the end-systolic volume of the control
      group and the experimental group were 72.55+/-8.13, 83.31+/-8.61 ml and 29.75+/
      5. 98, 46.25+/-6.68 ml, respectively (P<0. 05). The maximal velocity of peak E of
      control group and experimental group were 54. 85+/-6.35 cm/s and 43.14+/-4.81cm/s
      (P<0. 01); and the maximal velocity of peak A of control group and experimental
      group were 52.33+/-6.65 cm/s and 56.91+/-6.34 cm/s (P>0. 05). Echocardiography
      showing a distinctly dilatation of left ventricle with the ventricular dyskinesia
      in control group, but without the ventricular dyskinesia in experimental group.
      The selective-coronary angiography revealed that the obvious compensatory
      circulation established between the anterior descending branch and the left
      circumflex branch in the experimental group. CONCLUSION: Implantation of the
      autologous MSCs enriched by the SIS film can prevent dilatation of the left
      ventricular chamber and can improve the contractile ability of the myocardium,
      cardiac function, and collateral perfusion.

PMID- 17228694
TI  - [Effects of basic fibroblast growth factor gene transfection on biochemistry of
      meniscal fibrochondrocytes].
AB  - OBJECTIVE: To explore the effects of the basic fibroblast growth factor(bFGF)
      gene transfection on the meniscal fibrochondrocytes with the reconstructed
      lentivirus and to observe the response of the meniscal fibrochondrocytes to the
      bFGF gene transfection. METHODS: The cultured meniscal fibrochondrocytes were
      isolated from the same 3-month-old New Zealand rabbit. The cultured first
      generation meniscal fibrochondrocytes were divided into 3 groups:Group A
      (experimental group), Group B (control group), and Group C (blank group). Each
      group comprised the cells in a 24-hole flask in which each hole contained 2 x
      10(4) cells. At the confluence of 60%, the fibrochondrocytes in Group A were
      cultured with the reconstructed lentivirus carrying the bFGF gene. The
      fibrochondrocytes in Group B were cultured with the lentivirus carrying no bFGF
      gene. The fibrochondrocytes in Group C were cultured without any intervention.
      After 48 h, the cell cycle, the collagen synthesis ability, the expression of
      bFGF, and the cell proliferation ability in each group were investigated.
      RESULTS: In Group A, the bFGF expression of 870+/-60 pg/ml was detected in the
      cells 48 h after the co-culture; however, in Group B and Group C, no expression
      of bFGF was found. After the co-culture for 6 days, the results of the MTT
      colorimetry revealed that the cells in Group A had an absorptance of 0.427 +/
      0.037, which had a significant difference when compared with that in Group B and
      Group C (0.320+/-0.042, 0.308 +/-0. 034,P<0. 01). The cell cycle was
      significantly shorter in Group A than in Group B and Group C (P<0. 05); The
      durations of G, S and G2M of the cells in Group A were 16.28, 12.60 and 11.04 h,
      but those in Group B and Group C were 23.61, 16.90, 21.33 h and 21.56, 19.80,
      21.41 h, respectively. The disintegration per minute of the cells was
      significantly greater in Group A than in Group B and Group C (7 281.69+/-805.50
      vs 5 916. 40+/-698. 11 and 5 883. 57 +/-922.63.P<0. 05). CONCLUSION: The
      lentivirus vector can transfer the bFGF gene into the meniscal fibrochondrocytes,
      resulting in an increase of the cell proliferation and the collagen synthesis.

PMID- 17228695
TI  - [Research advance and clinical application of mesenchymal stem cells].
AB  - OBJECTIVE: To review the advance in the experimental studies and evaluate the
      potential therapeutic application of the mesenchymal stem cells (MSCs). METHODS:
      The related articles published in China and the other countries during the recent
      years were extensively reviewed and analyzed. RESULTS: The MSCs were widely used
      in the cell-transplantation therapy and the tissue engineering because of their
      pluripotency of differentiation into various kinds of cells. They were also
      frequently used in the gene therapy because they could stably express the
      transfected objective genes. Because of their immunomodulatory function, the MSCs
      could also be used in the immunotherapy. CONCLUSION: The MSCs are the stem cells,
      which have characteristics of renewing themselves, having multipotency, and being
      easy to undergo amplification in vitro. The MSCs are ideal target cells for the
      cell therapy, tissue engineering, gene therapy, and immunotherapy.

PMID- 17228696
TI  - [Review on progress of facial allotransplantation].
AB  - OBJECTIVE: To review the current progress of human facial allotransplantation in
      China and the METHODS: The recent literature concerned with human facial
      allotransplantation was extensively other countries. RESULTS: According to the
      literature reviewed, the main issues could be divided into reviewed and briefly
      summarized. four categories: technical aspects, immunological aspects,
      psychological and social issues ethical and legal problems related to facial
      allotransplantation. However, because of the complexity of the human facial
      allotransplantation, which involved many problems related to immunity,
      psychology, society, ethics, etc., there was much controversy in this field.
      CONCLUSION: In spite of the existent problems, facial allotransplantation in
      humans has still benefited the patient whose face is severely disfigured.

PMID- 17228697
TI  - [A preliminary study on the extraction method of velocity pulsated signals in the
      velocity spectrum image of pulsed Doppler ultrasounds in vitro].
AB  - Focus on the defects of the extraction method of velocity pulsated signals in the
      velocity spectrum image of pulsed Doppler ultrasounds (such as the limited data,
      great amount of work and low reproducibility), we combine the earlier research
      results and the basic rules of the velocity spectrum image, and employing the
      visual basics plateau, to design and develop a software to extract the velocity
      signals from the spectrum image automatically. Compare the mean velocity and RNS
      between the PIV and the PDU resulting from the method, the correlations are r =
      0.93 and r = 0.78 respectively. The study reveals the software increase the
      amount of valid data, decrease the amount of work and increase reproducibility of
      the signals extraction. The method may be an effective way to analyse the
      velocity spectrum image of PDU in clinic.

PMID- 17228698
TI  - [Variation regularization algorithm in electrical impedance tomography].
AB  - In this paper, a variation function has been introduced as a regularization
      penalty term in electrical impedance tomography (EIT) image restoration, which
      becomes to be the variation regularization algorithm. The key difference with
      Tikhonov regularization algorithm is that the variation regularization algorithm
      not only ensures the inverse problem well-posed but also increase the dividing
      line between the goal region and the background region of restored image clearer.
      This made the restored image in good accord with the medical image. It has
      significance to utilize EIT technique.

PMID- 17228700
TI  - [Three dimensional reconstruction of the nasal cavity structure and numerical
      simulation of airflow].
AB  - The nasal cavity structure of one patient was reconstructed by the method of
      surface rendering based on his CT images. In a respiratory period the change of
      air flux in the nasal cavity was supposed based on the tidal volume and the
      respiratory period gained by statistical method. The digital simulation and the
      analysis of the airflow in the nasal cavity was made by the FEA method and the
      result was compared with the data from literatures. The comparison indicates that
      the result is confident. From the result we can observe the airflow distribution
      quantitatively in the nasal cavity in the period of respiration.

PMID- 17228699
TI  - [Multiple analysis of the relationship between correlation of gene function and
      expression by GeneHub software].
AB  - GeneHub software developed by us can be applied to evaluate the significance of
      expression similarity of genes in each functional unit of different gene function
      classification systems, and thus to select experiment condition related gene
      functional units. With different expression similarity measurement and different
      experiment data, we have applied GeneHub to analyze the expression correlation of
      functional related genes classified respectively with gene chromosome location,
      celluar location and interaction, metabolic pathway and signal transduction
      pathway relationship of protein products of genes. Genes classified according to
      these multiple ways all showed significant experimental condition related co
      expression in our analysis. Our results provide further evidence for the
      assumption that functional related genes express similarly, which is widely
      adopted in gene expression profile analysis.

PMID- 17228701
TI  - [Segmental active contour model combining regional information].
AB  - A segmental active contour model integrating region information is proposed.
      Different deformation schemes are used at two stages for segmenting the object
      correctly in image plane. At the first stage the contour of the model is divided
      hierarchically into several segments, each of which deforms respectively using
      affine transformation. After the contour deforms to the approximate boundary of
      object, a fine matching method using statistical information of local region to
      redefine the external energy of the model is used to make the contour fit the
      object's boundary exactly. The algorithm is effective, as the reformative
      approaches of computing the internal energy and external energy are proposed to
      reduce the algorithm complexity. The experimental results indicate that the
      proposed model is robust to local minima and able to search for concave objects.

PMID- 17228702
TI  - [A computer simulation research for the effects of dragon's blood and its
      component loureirin B on sodium channel in dorsal root ganglion cells].
AB  - Using patch clamp technique the effects of dragon's blood and its component
      loureirin B on tetrodotoxin-sensitive sodium channel currents in dorsal root
      ganglion cells were observed. The experimental data were simulated with Hodgkin
      Huxley model and the corresponding parameters were estimated. In addition,
      computer-simulated neuron action potentials in the absence and presence of drugs
      were produced using Hodgkin-Huxley model. The results show that the conductance
      of tetrodotoxin-sensitive sodium channel was fitted with m3h model well, the half
      activated potentials of the sodium channel in the presence of drugs were shifted
      to the depolarizing direction and the threshold intensity of the cells in the
      presence of drugs was increased. These results demonstrate that dragon's blood
      and loureirin B did not resemble the tetrodotoxin which inhibited tetrodotoxin
      sensitive sodium channel currents completely. Perhaps the analgesic effects of
      dragon's blood were partly caused by loureirin B affecting the activation,
      blocking the action potential generation and interfering with the transmission of
      painful signals into the central nervous system.

PMID- 17228703
TI  - [A quality controllable algorithm for ECG compression based on wavelet transform
      and ROI coding].
AB  - This paper presents an ECG compression algorithm based on wavelet transform and
      region of interest (ROI) coding. The algorithm has realized near-lossless coding
      in ROI and quality controllable lossy coding outside of ROI. After mean removal
      of the original signal, multi-layer orthogonal discrete wavelet transform is
      performed. Simultaneously,feature extraction is performed on the original signal
      to find the position of ROI. The coefficients related to the ROI are important
      coefficients and kept. Otherwise, the energy loss of the transform domain is
      calculated according to the goal PRDBE (Percentage Root-mean-square Difference
      with Baseline Eliminated), and then the threshold of the coefficients outside of
      ROI is determined according to the loss of energy. The important coefficients,
      which include the coefficients of ROI and the coefficients that are larger than
      the threshold outside of ROI, are put into a linear quantifier. The map, which
      records the positions of the important coefficients in the original wavelet
      coefficients vector, is compressed with a run-length encoder. Huffman coding has
      been applied to improve the compression ratio. ECG signals taken from the MIT/BIH
      arrhythmia database are tested, and satisfactory results in terms of clinical
      information preserving, quality and compress ratio are obtained.

PMID- 17228704
TI  - [Investigation on the technique of three dimensional reconstruction and analysis
      of series slices of images].
AB  - The new techniques of three-dimensional (3D) reconstruction and segmentation,
      display and analysis of series slices of images including microscopic wide field
      optical sectioning by deconvolution method and Cryoelectron microscope slices by
      electron tomography (ET) and series of computed tomography (CT) were
      investigated. As a result, this paper presents the 3D reconstruction segmentation
      display, and analysis results of pollen spore, chaperonin, head, cervical
      vertabra, tibia and carpale. Mean while, this paper also proposes the application
      of these new techniques in biomedical field.

PMID- 17228705
TI  - [Electrocardiographic signal feature extraction and its instrument development
      based on continuous wavelet transform].
AB  - This paper introduces a virtual recording and analysis instrumentation system for
      recording and identifying electrocardiographic (ECG) signals. The system
      developed is aimed at constructing a PC-based virtual instrumentation which
      enables to record. investigate and measure the ECG signal of 12 leads
      simultaneously and perfectly in order to improve the measuring precision of ECG.
      Based on the proper feature in time domain of Mexican hat wavelet expressed by
      positioning and analysis precision for QRS complex, the instrumentation system
      uses continuous wavelet transform(CWT) and uses the Mexican hat as the wavelet
      base to measure precisely the characteristic information and generate the precise
      characteristic parameters of ECG. The analysis of measured ECG signals in
      hospital demonstrated that even in the condition with serious noise interference,
      the method presented is still easily to describe the characteristics of ECG on
      line precisely which makes the instrumentation system valuable in practical
      application.

PMID- 17228706
TI  - [A research on iteration stopping time of anisotropic diffusion].
AB  - Anisotropic diffusion has good effect on reducing noise and preserving edge, in
      fact it's an iterative process. An important question is to decide when the
      process should be stopped. The stopping time is chosen by minimal mean square
      error, signal-to-noise ratio and minimal correlation coefficient based on the
      information of the original (ideal) images and noises. The entropy and mutual
      information in information theory is adopted to develop a criterion on stopping
      diffusion process. The performance of the different criterions is proved by
      experiments, the specialty and the applying condition is also discussed.

PMID- 17228707
TI  - [Comparison of heart rate variability in healthy young men during exposure to
      different altitudes].
AB  - The characteristics of cardiovascular autonomic nerve system(ANS) modulation
      during exposure to three different altitudes were compared by time domain,
      spectral and nonlinear analysis of short-(5 minutes)term heart rate variability
      (HRV). The standard deviation of all RR intervals (SDNN), the square root of the
      mean squared differences of successive RR intervals (rMSSD), the percentage of
      successive interval differences >50 ms (PNN50), low frequency (LF), high
      frequency power (HF), and total power (TP) at 2800 m were slightly higher than
      those at 1856 m, but the differences were non-significant statistically. SDNN,
      rMSSD, LF and HF at 3040 m were significantly lower than those at 1856 m and 2800
      m. These results show that parasympathetic nerve activity decreases
      significantly, and ANS modulation is blunted after exposure to higher altitude.
      This kind of change of ANS may contribute to further elucidate pathophysiology in
      body after exposure to high altitude.

PMID- 17228709
TI  - [The algorithm of extracting respiratory information from single channel
      electrocardiogram].
AB  - Because the factors of interference in R wave of normal QRS are few except for
      respiration, the algorithm uses supra ventricular beats in the ECG to extract
      respiratory signal (EDR) (ECG-derived respiratory signal). The method used here
      firstly transfers the original single lead ECG signal into the wavelet, then
      prolongs R amplitudes of supra ventricular beats in the proper scale
      approximation of wavelet, then the prolonged signal passes a low pass filter,
      then reduces sample rate to 5 Hz, finally through a band pass filter (0.1-0.4
      Hz), the output of the band pass filter is the EDR.

PMID- 17228708
TI  - [The experimental research for dielectric spectroscopy of human blood cells].
AB  - The dielectric spectroscopy of human blood cells was measured within the
      frequency range of 0.01-100 MHz, and the dielectric numerical characters were
      determined as response to AC electric field. we measured the AC impedance of
      normal human blood cells with the impedance technique in the frequency domain,
      then the experimental data were drawn a relationship curve between the frequency
      of electric field and conductivity. The dielectric spectrum and the Cole-Cole
      plots of human blood cells were established. The characteristics of dielectric
      response of human blood cells were also established. The permittivity and the
      conductivity of human blood cells were frequency dependent, and dielectric
      dispersion of human blood cells had two characteristic frequencies: i.e. fc1, is
      1.42 MHz, and fc2 is 3. 32 MHz.

PMID- 17228710
TI  - [Multiple dipole source localization from spatio-temporal EEG data by Quasi
      Newton-ICA method].
AB  - We have investigated spatio-temporal source modeling (STSM) of the
      electroencephalogram (EEG) by using a Quasi-Newton method based on Independent
      Component Analysis (ICA) for localization of multiple dipole sources from the
      scalp EEG. The problem of multiple dipole localization was transformed into
      several single dipole localization problems. Another benefit of the present
      method is that the number of independent sources can be estimated. Computer
      simulation studies were conducted to evaluate the performance of this approach.
      The present simulation results indicate that the ICA-based method is superior to
      the conventional nonlinear methods in localization accuracy, computation time and
      anti-noise performance, for multiple dipole localization when the sources are
      stationary over the period of interest.

PMID- 17228711
TI  - [A blood speckle reduction method based on temporal-spatial relativity of
      intravascular ultrasound].
AB  - The superior imaging manner of intravascular ultrasound becomes more and more
      widely used in the diagnosis of coronary heart disease and intervention therapy.
      However, as the frequency of ultrasound increases, strong speckled echo signal
      from blood may significantly decrease the contrast of lumen and arterial wall
      structure, which may make it difficult for doctor to diferentiate and measure
      geometrical parameters and physical parameters of lumen and plaque. In this paper
      a novel noise reduction method is introduced, which utilizes the temporal and
      spatial information of IUVS, that is blood echo speckles have higher temporal and
      spatial variation than the arterial wall. When signals transferred into the
      frequency field, tissue and blood present different frequency spectrum, then a
      radio of high frequency energy and low frequency energy is introduced to
      determine speckles or tissue. Result showed that the method can remarkably remove
      the speckle noise, increase the contrast and help doctor differentiate the
      arterial wall from the around tissues.

PMID- 17228712
TI  - [A research of correlative analysis between EEG signal and the input-signal of
      the acupoints].
AB  - In this paper, different acupoints are stimulated by using pulse stimulating
      signals with different frequency. The correlation between input signal from
      acupoints and output signal from brain band is studied. A method to optimize
      input of acupoints is obtained by an experiment system. And the dynamic
      connection between meridian and brain band is identified. Experiment has shown
      that there exists maximal correlation between the signal of 30 Hz intermittent
      pulse stimulation and the induced cerebral alpha band. And the 30 Hz intermittent
      pulse stimulation can induce more beneficial cerebral a band.

PMID- 17228713
TI  - [Extraction of single-trial event-related potentials by means of ARX modeling and
      independent component analysis].
AB  - The present paper focused on the extraction of event-related potentials on a
      single sweep under extremely low S/N ratio. Two methods that can efficiently
      remove spontaneous EEG, ocular artifacts and power line interference were
      presented based on ARX modeling and independent component analysis (ICA). The
      former method applied ARX model to the measured compound signal that extensively
      contained the three kinds of ordinary noises mentioned above, and used ARX
      algorithm for parametric identification. The latter decomposed the signal by
      means of independent component analysis. Besides, some of ICA's important
      decomposing characters and its intrinsic causality were pointed out definitely.
      According to the practical situation, some modification on FastICA algorithm was
      also given, so as to implement auto-adaptive mapping of decomposed results to ERP
      component. Through simulation, both the two ways are proved to be highly capable
      of signal extraction and S/N ratio improving.

PMID- 17228714
TI  - [Application of the combined use of uniform experimental design and orthogonal
      experimental design in biomedicial engineering].
AB  - A new optimized experimental designing method in biomedical engineering study is
      provided in this paper. The characteristic of the uniform design and orthogonal
      design was compared. Then, a new experimental design was proposed, which was the
      combined use of the two experimental designs. Discussed the theoretical basis,
      using method and its advantages. Furthermore, we proved the validity through our
      experiment. This method has the specificity of uniform design, fewer times of
      experiment and suit for experiment with multi-factors and multi-levels. This
      makes full use of the advantages of orhtogonal design which is widely used and
      can be analyzed by simple intuitionist analysis, avoids the disadvantages of
      uniform design in which data can only be processed by computer software. It can
      be widely used in the research and development of biomedicine engineering.

PMID- 17228715
TI  - [Classification of surface EMG signal based on wavelet transform with nonlinear
      scale].
AB  - Surface EMG (sEMG) signal is a complex nonlinear, non-stationary signal. In this
      paper, wavelet transform with nonlinear scale (NWT) is introduced. Due to the
      gradual shortening of its time-resolution, NWT is good at extracting the precise
      time-frequency information from sEMG signal. First, every sEMG signal (30 sets
      are for forearm supination and 30 sets are for forearm pronation) is transformed
      into intensity distribution (time-frequency distribution) by NWT. And then the
      feature vector is determined from the characteristic roots which are obtained
      from the intensity distribution by principle component analysis. At last, the two
      patterns of sEMG signals are identified by BP neural network. The results show
      that the accurate classification rate is higher gained by NWT than by two
      conventional time-frequency distributions. At the same time, the calculating
      complexity of neural network is decreased greatly.

PMID- 17228716
TI  - [The recognition of breast tumor based on ultrasonic image contour features].
AB  - The purpose of this article is to evaluate the role of quantitative margin
      features in the computer-aided diagnosis of malignant and benign solid breast
      masses using sonographic imaging. The tumour was seperated by the expert. Three
      contour features circurity (C), area ratio (A) and length width ratio (LWR) was
      caculated from the tumour contour. Then back-propagation (BP) neural network with
      contour features was used to classify tumors into benign and malignant. Results
      from 119 ultrasonic images have been applied in this experiment. BP neural
      network yielded the following results: 89.7% and 73.5% respectively. The methods
      applied in this paper are helpful to raise the correctance of breast cancer
      diagnosis.

PMID- 17228717
TI  - [Hemodynamics analysis of intravascular stents with different design features].
AB  - Wall shear stress plays an important role in the development of in-stent
      restenosis. It has been demonstrated that low wall shear stress. is associated
      with neointimal hyperplasia. We used computational fluid dynamics (CFD) to
      investigate the steady and pulsatile flows in the vicinity of model stents and
      focused on the changes of wall shear stress caused by the implanted stents. The
      results showed that wall shear stress depended greatly on the size and structure
      of the stents, which would have implications for the optimization of
      intravascular

PMID- 17228718
TI  - [Finite Element Analysis (FEA) for the structure capacity of proximal femur
      during falling--(II). The effects of falling configuration and load locations on
      the structural capacity of the proximal femur].
AB  - The effects of loading conditions on the structural capacity of the proximal
      femur were investigated parametrically by Finite Element Analysis (FEA) combined
      with Hoffman failure criterion. The loading conditions included the fall
      configuration angles, load locations and the friction resistance in hip joint.
      The results of this parametric study revealed that the load locations are the
      keys to determining the structural capacity of the proximal femur. There are two
      low peaks of the structural capacity when the loads are applied to femoral head.
      If the impact load were applied in this area, the fracture risk would be great.
      The frictional resistance of the hip joint can severely affect the failure load,
      which has far reaching implications in terms of osteoarthritis.

PMID- 17228719
TI  - [The reconstruction of three dimensional nonlinear finite element model of L3-L5
      motion segment].
AB  - In this study, a detailed L3-L5, three dimensional nonlinear finite element model
      of a normal aged 32 man was established with the aid of two softwares, CATIAV5
      and MSC. Marc, which can derive a three-dimensional finite element model from CT
      images. We loaded the model with 10 N * m net moment and computed the average
      rigidity of functional spinal unit. The model was validated in contrast to the
      former biomechanical studies of cadaveric spine. The model will be used in
      further clinical biomechanical studies.

PMID- 17228721
TI  - [Finite element analysis of the expansion behavior of coronary stents].
AB  - Coronary stent is an important device used in Percutaneous Transluminal Coronary
      Angioplasty (PTCA) which is usually implanted to support the stenosed artery. Its
      expansion behavior depending on inflating of balloon and characters of recoil
      happening while the balloon is retrieved is the most important aspects which
      should be concerned in operation. In this paper, the finite element method was
      applied to systematically analyze the influence of strut width and thickness and
      the scale of dilatation of stent on its performance in expansion. The results
      show that increasing the strut width or thickness can improve the critical
      internal pressure needed for stent to expand fast. And the change of stent length
      while expanded is only associated with its structure and final dilatation state.
      If stent geometry is the same, it is the stent material that may be the main
      aspect to affect the recoil of stent. Experiment result is well consistent with
      simulation which indicates that the finite element method can substitute for the
      stent prototype testing to some extent.

PMID- 17228720
TI  - [The mechanical force analysis of cleft maxillary three dimensional finite
      element models after alveolar bone graft].
AB  - To investigate the biomechanical influences on two different cleft maxillary 3D
      finite element models pre- and post-alveolar bone graft, we developed a cleft
      palate bony model from a 17 year cleft palate male CT scan data and built an
      alveolar bone-grafted cleft maxillary 3D finite element model through gluing the
      graft model. Apply vector lip force on the anterior face of the models. Study the
      press (including S3 principal, S1 principal, von Mises and shear) distribution
      properties and localized area. The results suggested that the press principal
      spreads along the alveolar ridge and formed several focused areas. After bone
      grafted, the shear stress tends to be evenly. The grafted alveolar could resist
      the medially deformation of alveolar crest and the shear stress to the nasal base
      bony structure. The conclusions from results demonstrated that the deformation of
      alveolar ridge is possibly due to the lip pressure after the lip repair. The
      shear stress along the alveolar ridge could cause the severity of the dentition.
      The grafted bony structure could even the shear stress distribution evenly other
      than the distribution properties.

PMID- 17228722
TI  - [Preparation and characterization of Mn-Zn ferrite oxygene nanoparticle for tumor
      thermotherapy].
AB  - With the sulfate as the materials and NaOH as precipitator, Mn(0.4)Zn(0.6)Fe2O4
      nanoparticles were produced, which are proved to be spinel Mn-Zn ferrite analyzed
      by X-ray diffraction(XRD). Their shapes are approximately global examined by
      transmission electron microscopy(TEM) and their average diameter is 50 nm
      measured with image analysis-system. The Curie temperature was measured and in
      vitro heating test in a alternating magnetic field was carried out. The results
      show that the Curie temperature is 105. 407 degrees C, While its magnetic fluid
      could rise to 43 degrees C - 47 degrees C due to different concentration in a
      alternating magnetic field. The result provide theoretical and practical evidence
      to select an appropriate material and concentration for tumor

PMID- 17228723
TI  - [Study on modified guar gum microsphere as a protein drug carrier].
AB  - A biodegradable modified guar gum microsphere was prepared for the first time by
      ionic gelation of the guar gum derivative containing quarternary ammonium group
      with tripolyphosphate at room temperature in the absence of emulsifying agent or
      organic solvent. Its average particle diameter was about 140 microm and the
      particle size had a narrow and normal gauss distribution. From the loading
      experiment of bovine serum album (BSA) with various concentrations, it was found
      that the encapsulation efficiency is more than 80%. By the investigation of in
      vitro release from the BSA-loaded microsphere, it was found that the BSA had a
      continuous release for more than 6 hours and the release percentage was affected
      by the initial concentration of the BSA and temperature.

PMID- 17228724
TI  - [Structure and performance of calcium polyphosphate for bone tissue engineering].
AB  - Porous calcium polyphosphate (CPP) has shown promise of tissue engineered implant
      application because of the biocompatibility and biodegradation. CPP with
      different polymerization degree were prepared by controlling the calcining time,
      and its polymerization degree could be calculated by developed method in this
      paper. Different crystal types CPP were prepared by quenching from the melt and
      crystallization of amorphous CPP. From the in vitro degradation, carried out in
      Tris-HCl buffer, the degradation velocity of CPP was controllable. The weight
      loss of CPP with different polymerization degrees and crystal types were
      different. With the increasing of polymerization degree, the weight loss during
      the degradation was decreasing, contrarily the strength of CPP was increasing.
      The amorphous CPP could degrade completely in 17 days while gamma-CPP do
      completely in 25 days. The degradation velocity beta-CPP and alpha-CPP was slower
      than gamma-CPP and the weight loss was about 12% and 5% respectively. The results
      of this study indicate that CPP have potential applications for bone tissue
      engineering as inorganic polymeric biomaterials.

PMID- 17228725
TI  - [Security evaluation of subcutaneous injection with water-based dextran-coated
      magnetic fluid].
AB  - Water-based magnetic fluid was synthesized by using 50% dextran 40,000 as coated
      reagent. The acute toxicity and irritant of the magnetic fluid injected into mice
      subcutaneous tissues were examined. The lethal dosage 50 of dextran-coated
      magnetic fluid was 4409.61 +/- 514.93 mg/kg. Twenty four h after subcutaneous
      injecting with 30 mg/0.3 ml dextran-coated magnetic fluid, no more inflammation
      than hemangiectasia and leucocytes infiltration had been seen in subcutaneous
      tissues, 72 h later the reaction phenomena disappeared. While, injection with 30
      mg/0.3 ml water-based oleate sodium-coated magnetic fluid, ulceration and break
      off of cutis had been seen in the seventh days. That is to say, the dextran
      coated magnetic fluid was safe and well tolerate, however, the oleate sodium
      coated magnetic fluid was not fit to subcutaneous injection.

PMID- 17228726
TI  - [Surface modification and microstructure of single-walled carbon nanotubes for
      dental composite resin].
AB  - In order to improve its dispersion condition in dental composite resin and
      enhance its interaction with the matrix, single-walled carbon nanotubes(SWNTs)
      were refluxed and oxidized, then treated by APTE. Their outer surface were coated
      by nano-SiO2 particles using sol-gel process, then further treated by
      organosilanes ATES. IR and TEM were used to analyze modification results. TEM
      pictures showed nano-particles were on the surface of SWNTs; IR showed
      characteristic adsorbing bands of SiO2. Composite resin specimen with modified
      SWNTs was prepared and examined by TEM. SWNTs were detected in composite resin
      matrix among other inorganic fillers.

PMID- 17228727
TI  - [Changes of heart function after different cell type stem cell transplantation in
      chronic heart failure].
AB  - To investigate the feasibility of introcoronary cell infusion into nonischemic
      heart failure (HF) heart and whether different types of stem cell transplantation
      would affect heart function to a similar degree. Japanese white ears rabbits were
      used as HF models by intravenous injection adriamycin. Autologous bone marrow
      mononuclear cells(BMCs), bone marrow stromal cells (MSCs), skeletal myoblasts
      (SMs) or culture medium were infused into coronary arteries respectively by
      occluding the root of ascending aorta. The mortality during and 4 weeks after the
      procedure the mortality was 7.1% and 16.7% respectively. After 4 weeks, the
      ejection fraction (EF) in BMCs group had significant improvement (P < 0.05, n=8).
      No significant difference was seen in MSCs (n =8), SMs (n=6) and sham groups
      (n=8) compared with pretransplantation (P > 0.05). In sham group,the left
      ventricular endostolic diameter (LVED) had significant enlargement (P < 0.05), No
      significant difference was seen in MBCs, MSCs and SMs groups compared with
      pretransplantation (P > 0.05). Immunofluorescence revealed de novo expression of
      cardiac troponin I in BMCs and MSCs groups, cardiac troponin I was not detected
      in SMs group. In conclusions, intracoronary cell transplantation could provide
      effective cell delivery into dilated cardiomyopathy hearts and could be a useful
      strategy for treating CHF, BMCs cell transplantation may be the first choice in
      all the above cell types.

PMID- 17228728
TI  - [Cloning human heat shock protein 90beta-cDNA and constructing its eukaryon
      vector].
AB  - The purpose of this study was to clone human HSP90beta cDNA and construct its
      eukaryote expression vector . The total RNA was isolated by TRIzol Reagent
      (Invitrogen) from human NPC and its cDNA was gained by RT-PCR. The purified RT
      PCR products and PGEM-T Easy Vector were ligated and transformed into XL1-blue E.
      coli bacteria. The white clones were selected and the plasmid was purified, which
      was further identified by double enzyme digestion and sequenced. PGEM-hHSP90beta
      and pcDNA3.1(+) DNA were digested by AflII and Xbal respectively. After
      purification, the two fragments obtained were ligased by using T4 DNA ligase
      (Fermentas). This recombinant DNA was then transformed into E. coli Competent
      Cells XL1-blue and positive clones were selected on the LB agarose plate
      containing Ampr (100 microg/ml). Single clones were identified by double
      digestion with AflII and Xbal, and two fragments with the size 5.4 kb and 2.1 kb
      were produced as expected. The hHSP90beta gene was successfully inserted into the
      eukaryote expression vector pcDNA3.1(+) by the recombination technique in vitro.

PMID- 17228729
TI  - [Construction recombinant adenovirus vector expressing murine endostatin and
      inhibition of blood endothelial cells growth].
AB  - We constructed recombinant adenovirus vector expressing murine endostatin and
      evaluated the Inhibition of human umbilical vein endothelial cells (HUVEC). We
      proved that endostatin significantly suppressed the S phase fraction, inhibited
      proliferation and increased the apoptotic index of HUVEC.

PMID- 17228730
TI  - [Construction of the recombinant integrating shuttle plasmid with cfpl0-esat6
      fusion gene of Mycobacterium tuberculosis and its expression in BCG].
AB  - This study was conducted to amplify the cfpl0-esat6 fusion gene by SOE and insert
      into the integrating shuttle plasmid pMV361 to form the recombinant plasmid. Then
      another recombinant plasmid was constructed by insertinga-A g signal sequence of
      BCG. The two recombinant plasmids were introduced into BCG and the induced
      products from recombinant BCG were analyzed. In conclusion,the successful
      construction of rBCG expressing the fusion protein CFP10-ESAT6 will be the base
      of the development of novel Mycobacterium tuberclosis vaccines.

PMID- 17228731
TI  - [Anti-cervix-cancer effect of the co-immobilization of tumor necrosis factor
      alpha and interferon-gamma].
AB  - To explore the effect of the co-photo-immobilization of Recombinant Human
      Interferon-r (IFN-gamma) and Recombinant Tumor Necrosis Factor (TNF-alpha) on the
      Hela cell cultivated in vitro. Co-immobilize the photoactive IFN-gamma and TNF
      alpha on the polystyrene membrane; Cultivate the Hela cell on the cell culture
      polystyrene plate surface and set up the cultivation of the photo-immobilization
      IFN-gamma+TNF-alpha, Photo-immobilization IFN-gamma, nature (IFN-gamma, TNF
      alpha, IFN-gamma+TNF-alpha). After 48 hours, the inhibition effect against Hela
      cells was studied in vitro by SEM and flow cytometry. It showed that the co
      immobilization IFN-gamma+TNF-alpha has a more obvious inhibition effect on the
      Hela cell. And IFN-gamma can cooperate with TNF-alpha obviously.

PMID- 17228732
TI  - [A novel method of amplifying the heavy-chain variable regions from
      immunoglobulin cDNAs].
AB  - The amplification of variable regions (Fv) of immunoglobulins has become a
      crucial technique for studying antigen-antibody interactions and cloning the
      monoclonal antibodies (mAbs). But this work becomes a major challenge in cloning
      antibody genes either from hybridoma cell lines or B cells. Isolation of the
      immunoglobulin heavy-chain variable regions (VH) from two mouse hybridoma cell
      lines based on conventional protocols using both the specific consensus primers
      and the commercial primer set of VH regions, was unsuccessful. This prompted us
      to design our own primers for VH regions of immunoglobulins. A novel algorithms
      and reverse polymerase chain reaction (PCR) protocol--3' RACE and 5' RACE were
      established in order to recognize the VH genes. The most conserved region in the
      end of framework region (FR1) of the VH cDNA region was identified with the
      program and a degenerated primer were designed in the most conserved region
      followed by 3' RACE and 5' RACE. The new protocol rescued the failed PCR
      amplifications. Thereby, a improvement in the degenerate primers designing
      programs and a notable increase in amplification specificity were achieved. This
      approach can be useful in primer design and amplification of VH and light-chain
      variable regions (VL) gene libraries or cloning of the unknown genes in the large
      gene families and extend to other species or members of the immunoglobulin
      superfamily.

PMID- 17228733
TI  - [Effects of salidroside on bone marrow matrix metalloproteinases of bone marrow
      depressed anemic mice].
AB  - To examine the effect of salidroside on the expression and activities of matrix
      metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in bone marrow
      (BM) of BM depressed anemic mice by immunohistochemistry and gelatin zymography
      respectively, and to explore its roles in hematopoietic regulation.
      Immunohistochemistry showed that the expression of MMP-2 and MMP-9 of bone marrow
      cells (BMCs) was found in each group. Compared with control group, the expression
      of MMP-2 and MMP-9 was obviously increased in the model group, low-dose, middle
      dose and high-dose salidroside. At day 4 after treatment of radiation and
      chemotherapy, the peak of the expression of MMP-2 and MMP-9 was found in middle
      dose salidroside . At day 8 after treatment of radiation and chemotherapy, the
      peak of the expression of MMP-2 and MMP-9 was found in low-dose and middle-dose
      salidroside respectively. Gelatin zymography revealed that 66 kD proMMP-2, 62 kD
      MMP-2, 86 kD MMP-9 and 94 kD proMMP-9 were detected in control group, and the
      activity of MMP-9 was stronger among them. After treatment of radiation and
      chemotherapy, the activity of gelatinases of hemopoietic microenviroment (HM) was
      obviously decreased, but low-dose, middle-dose and high-dose salidroside could
      significantly increase the activities of proMMP-9 and MMP-9, attenuate the
      activity of proMMP-2. These results suggest that salidroside could promote the
      recovery of hematopoietic function of BM depressed anemic mice by increasing the
      expression and activity of MMPs, releasing the cytokines from ECM or cell
      membrane, repairing impaired microvessels of HM and promotion proliferation,
      migration and differentiation of HSCs.

PMID- 17228734
TI  - [Construction of scFv antibody mini-library to 3 cellular surface molecules].
AB  - To construct a scFv antibody mini-library by phage display technique from the
      spleen cells of BALB/c mice immunized with extracellular domain of N-cadherin (N
      cad), CD34 and AC133, the extracellular domain genes of N-cad, CD34 and AC133
      were cloned into a phagemid pSEX81 respectively, and were then displayed on the
      phagemid in the form of fusion protein with p III protein. After being
      effectively immunized with the fusion protein, the spleen of the mice were
      harvested, and total RNA were extracted from the spleen. The cDNA of VH and VL
      genes were amplified by RT-PCR, and a scFv-phage display antibody library was
      constructed with the amplified V-genes. The content, multiplicity and expressing
      potential of the library were examined. As a result, we had produced a scFv
      library containing 1.4 x 10(6) individual clones which showed different patterns
      after being digested with restriction endoneuclease Mua I. The surface display
      expression of the library was also verified. It indicated that the capacity and
      diversity of the library was sufficient for screening specific scFv antibody
      against N-cad, CD34 and AC133. The library will be useful for isolating
      corresponding specific scFv antibodies.

PMID- 17228735
TI  - [Fluorescence spectra and test application study on the interaction of
      fluorescein and bovine serum albumin].
AB  - A fluorescence method is found for determination of bovine serum albumin (BSA).
      The method is based on the interaction of fluorescein with BSA to form a complex
      in Tris-HCl buffer of pH 2.2. The complex exitation wavelength is 467 nm, the
      emission wavelength is 515 nm. The linear measurement rang is between 1.8-500
      mg/L for BSA, F = 26.776 C + 2.8082, r = 0.9999. This method is
      sensitive,steady,and low cost for determination of BSA.

PMID- 17228736
TI  - [Study on allergenicity of fresh HAM for type I hypersensitivity].
AB  - To investigate whether human amniotic membrane (HAM) preparations have the
      possibility to type I hypersensitivity and its allergenicity. In systemic active
      allergic test model, 30 guinea pigs were equally divided into three groups. Each
      10 guinea pigs were immunized with fresh HAM homogenate, albumen solution
      (positive control) and PBS (negative control). After the animals were stimulated
      with corresponding allergen, observe their reaction till dying or 3 h, then
      obtain blood samples, to determine blood histamine concentrations using chemical
      fluorometry and four hemorheologic markers by hemorheology analysis system. The
      guinea pigs responded to fresh HAM homogenate in almost the same manner as to
      PBS, and no obvious allergic reaction was observed in the animals except those in
      positive control group. The blood histamine concentration and four hemorheologic
      markers showed no significant differences between HAM and PBS (P > 0.05), both
      were much lower than positive control group (P < 0.01). Fresh HAM won't lead to
      type I hypersensitivity for lack of allergen performance.

PMID- 17228737
TI  - [Research of contour analysis on endoscopy navigation].
AB  - In this paper, a new method of contour analysis is presented to find path in
      endoscopy navigation. At first, edge detection is used to endoscope image. Then
      we do skeleton extraction and connect the edge skeleton to contours by grouping
      criteria. At last we can get navigation information by analyzing the contours.
      Experiments show that this algorithm has good precision and stability.

PMID- 17228738
TI  - [Study on an optimized patch probe and its biomedical application].
AB  - A wide-band patch probe excited by coaxial line, which is useful for noninvasive
      measurement of superficial tissues at high frequencies, is presented in this
      paper. Optimization of the probe is performed by genetic algorithm (GA) combined
      with Finite Difference Time Domain (FDTD). Then the optimized round patch probe
      is used to measure reflection coefficient for 1-7 GHz. The measured results show
      some interesting phenomena, which are very useful for reconstruction of electric
      properties of superficial tissues.

PMID- 17228739
TI  - [The temperature control for cancer thermotherapy using interstitial microwave
      antenna].
AB  - The basic objective of microwave hyperthermia is to raise the temperature in the
      tumor tissue without overheating point for a long time. It's difficult to achieve
      uniform temperature distribution using the continuous heating without changing
      the antenna shape and inserting position. In this paper, the interstitial antenna
      worked in the frequency of 2450 MHz inserted into an infinite muscle model is
      studied. The Finite Difference Time Domoin (FDTD) method was used to calculate
      the electromagnetic field, while the finite difference method (FDM) was used to
      analyze the temperature distribution in tumor tissue. The simulation results show
      that the long-time evenly heating can be achieved by using the alternately
      heating process and the treatment area can be changed by adjusting input power.

PMID- 17228740
TI  - [Design and implementation of aphasia rehabilitation software based on speech
      recognition].
AB  - A new software therapy instrument is proposed for the rehabilitation of aphasia
      caused by cerebral disorder, which is different from general drug therapy or
      physical therapy and is, based on modern speech and biofeedback principles.
      Aphasia rehabilitation software package on the therapy instrument were designed
      and implement. The features of the software and its future application were
      discussed.

PMID- 17228741
TI  - [QRS complexes detection based on Mexican-hat wavelet].
AB  - In this paper, we using Mexican-hat wavelet transform to detect characteristic
      points of ECG signal based on the characteristic points corresponding with the
      extremes of Mexican-hat wavelet transform. It offers a new detection method of
      ECG signal analysis. This method is simple and it is proved to be accurate and
      reliable. The correct rate of QRS detection rate examined by the MIT-BIT
      arrhythmia database rises up to 99.9%.

PMID- 17228742
TI  - [Study on all-round evaluation of biocompatibility of biomaterial].
AB  - Biocompatibility has always been the focal point in the study of biomaterials
      applied to medical apparatus. But at present, the standard system hasn't formed
      completely to evaluate the biomaterials. In recent years scientists tend to use
      general standard of evaluation. In this article, based on the recalcification
      time, the adhesion of platelets as well as the total quantity of plasma protein
      and some other evidences, combining with the Analytic hierarchy process (AHP),
      the method of general evaluation on the biocompatibility of anticoagulant
      biomaterials was discussed.

PMID- 17228743
TI  - [The cell micro-encapsulation techniques and its advancement in the field of gene
      therapy].
AB  - It is no doubt that the gene therapy using recombinant engineering cells provides
      a novel approach to many refractory diseases. However, the transplant rejection
      from the host's immune system against heterogeneous cells has been the main
      handicap of its clinical application. The modern cell micro-encapsulation
      technique with good immune isolation makes it possible to overcome this problem
      and has shown potential application foreground in clinical therapies for a lot of
      diseases such as Parkinson's disease and Hemophiliac disease. This article
      reviews mainly the relative materials and techniques in processing micro
      encapsulation, the host cells used to construct the recombinant genetic
      engineering cells and application of cell micro-encapsulation technique in the
      field of gene therapy.

PMID- 17228744
TI  - [Stem cell and repair of injury in central nervous system].
AB  - All of neural stem cell within the central nervous system and derived from
      transplantation or embryonic stem cell have the ability of differentiating into
      various kinds of neural cells. Regeneration of neural cells plays a critical role
      on function recovery damaged central nervous system (CNS). Advances in repairing
      of injury in central nervous system with neural stem cell and embryonic stem cell
      in recent years are reviewed in this article.

PMID- 17228745
TI  - [Effect of overload environment on IGF-1 expression of osteoblasts].
AB  - In the study of the relationship between cells overloading and the formation,
      regeneration and growth of bone, the text discussed osteoblasts express IGF-1
      variation under overloading environment. The research of overloading on cellular
      level may elucidate the mechanical effect on the formation, regeneration and
      growth of bone and the mechanism of cell response in bone.

PMID- 17228746
TI  - [The research progress in intravascular stent endothelialization].
AB  - Since the introduction of percutaneous transluminal coronary stenting, restenosis
      has remained the most challenging problem facing interventional cardiologist.
      Recently, evidences indicate that endothelial cell, especially endothelial stem
      cell planting stent might provide more insights. In this review several factors
      related to stent endothelialization are discussed.

PMID- 17228747
TI  - [Progress in research and application of time-resolved optoacoustic method in
      biomedicine].
AB  - Based on optoacoustic effect, time-resolved optoacoustic technique effectively
      combines optical technology with acoustic technology and partly overcomes the
      biological tissue's scatter characteristics which might influence the results of
      measurement. Optoacoustic technique has the advantages of high sensitivity and
      high resolution and has been widely applied in biomedicine field. In this paper,
      the measuring principles, the key technique, application and future direction of
      this technique are synthetically reviewed to promote the research in theory and
      application in the future.

PMID- 17228749
TI  - The state of our health.

PMID- 17228748
TI  - [Progress of silk fibroin in the cell scaffold of tissue engineering].
AB  - Recent researches about the application of silk fibroin in cell culture suggested
      that silk fibroin displayed high rate of cell attachment and growth in vitro
      culture of most kinds of cells, equivalent to collagen. So silk fibroin can be
      used for cell scaffold material of tissue engineering, and can be applied to
      several fields such as tissue engineering of skin, cartilage and blood vessel.
      The related researches and the prospect of the application of silk fibroin in
      cell scaffold of tissue engineering are reviewed in this paper.

PMID- 17228750
TI  - [QOL research in child health. Present state and issues].
AB  - The evaluation of QOL (Quality of Life) in the medical field has revolved around
      the development of self-measurement scales comprising two or more questions based
      on psychometric theory. QOL research in the field of child health progressed in
      the latter half of the 80s in the United States, and aspects of ambiguity and
      adaptation to the environment of children were recognized. Objective health and
      subjective health differ significantly among children and are strongly influenced
      by environmental factors. In addition, QOL in early life anticipates the later
      health status in adolescence and youth. For these reasons, QOL research in the
      field of child health is very important. More than 20 scales, exemplified by CHQ,
      PedsQL, TACQOL/TAPQOL, and COOP charts, exist as standard generic QOL indices for
      children. Disease-specific scales cover epilepsy, asthma, and allergic disease,
      as discussed in a number of early studies. Diabetes, skin disease, and cancer are
      also major research subjects. Self-evaluation is one of the principles of QOL
      research; it is stated that children in the age group of 5-6 years are already
      capable of expressing pain and their physical condition and that the competency
      to describe abstract concepts such as pride and happiness matures around the age
      of 9-10 years. Sources of information such as the computer have developed and
      spread remarkably in recent years. The use of such technology facilitates the
      evaluation of young children with a high level of accuracy. The problems
      currently faced are the low reliability of responses of children, difficulties in
      cross-cultural comparison, and transformation of the sense of values according to
      growth. In conclusion, the development of QOL research in the field of child
      health should allow realization of an improved health situation in which
      children's points of view are included in the decision-making process for
      required treatments and health care policy. Further, health administration can be
      expected to thereby become more effective and balanced.

PMID- 17228751
TI  - [Contingent valuation for health care services. Review of domestic studies and
      outline of foreign investigations].
AB  - Contingent valuation method (CVM) can be applied to measure benefits of
      healthcare services. It is a technique for estimating subjects' willingness to
      pay (WTP) for a service under the scenario describing a virtual market with a
      questionnaire. In the present research, we outlined foreign studies and reviewed
      domestic studies on healthcare contingent valuation. A total of 14 papers from
      domestic literature (five English and nine Japanese articles) identified with
      mechanical search engines were verified for the following eight items: the method
      of the questionnaire; the information included in the virtual scenario; the
      question form for the willingness to pay; bias problems specific to CVM;
      validity/reliability, ex post/ex ante valuation, altruistic WTP, and non-health
      value. The following conclusions were drawn from the domestic studies: (1)
      several studies were short of sufficient information regarding the virtual
      scenario; (2) no research proved the existence of bias and the ways of coping
      with it; (3) tests for reliability were not carried out, although some kind of
      validity was verified; (4) all involved ex post user based evaluation; (5)
      neither altruistic WTP nor non-health value was examined. Taken the advantages of
      CVM into consideration, it should become a useful tool, complementing other
      economic evaluation techniques. Since its application has just begun in Japan,
      more emphasis needs to be given to practical issues so that healthcare workers
      will utilize CVM in a way that domestic studies in health economics will be
      activated.

PMID- 17228752
TI  - [Parenting anxiety and childhood development of twins as compared to singletons].
AB  - OBJECTIVE: Parenting anxiety has been highlighted recently because it tends to be
      a problem of mother-child relationships and a factor in child maltreatment.
      Compared to mothers of singletons, it is reported that mothers of twins
      experience a greater physical and mental burden of parenting. This study aims to
      investigate whether mothers of twins have more parenting anxiety than those of
      singletons and whether parenting anxiety affects child's mental development in
      both twin and singleton groups. METHODS: 218 mothers of 0 to 2-year-old twins
      were recruited at seventeen organizations for twin rearing in Kinki area, western
      Japan, from March to May 2005. Questionnaires were mailed or handed out to the
      mothers. In all, 124 mothers of twins (56.9%) returned the questionnaires. 5 data
      sets were excluded because of twins' cerebral paralysis or other reasons and 119
      data sets (96.0%) were analyzed. A total of 348 mothers of singletons were
      collected at four preschools and two public health centers in the same area from
      March 2005 to March 2006. Questionnaires were mailed or handed out and were
      returned by 101 mothers (28.1%). 4 data sets were excluded because of the
      presence of twins or over age children and 97 data sets (96.0%) were analyzed.
      The core questionnaires included the JCFRI Child Rearing Support Questionnaire
      for measurement of parenting anxiety and the Tsumori-Inage Infant Developmental
      Scale. RESULTS: 1. Compared to their counterparts with singletons, mothers of
      twins showed significantly higher scores for parenting anxiety, including general
      confusion of parenting and negative feelings toward their children. 2. On
      multiple logistic regression analysis, high parenting anxiety in mothers of 2
      year-old twins, especially negative feelings were related to delay in the
      children's mental development. However, there was no significant relationship
      with twins aged 0 or 1 year and with singletons of 0 to 2 years of age.
      CONCLUSIONS: The results suggest that negative feelings toward children influence
      mother-child interactions and complicate relationships. Parenting anxiety is a
      severe problem in mothers of twins not only because it causes mental problems in
      mothers but also because it has an impact on child mental development.

PMID- 17228753
TI  - [Latent factors generating health behavior and health consciousness].
AB  - PURPOSE: The purpose of the present study was to explore structural relationships
      among health behavior and health consciousness and to delineate latent factors
      underlying them. METHODS: Data used in this study were obtained from a mail
      survey conducted by Toshima City Government, Tokyo, in 2002. The subjects were
      3,000 community residents, living in the city, ranging in age from 20 to 79
      years. The response rate was 54.3%. The data for 1,301 respondents without
      missing observations were analyzed. A second-order factor model utilizing 23
      items of health behavior and health consciousness as observed indicators was
      developed for the analysis. RESULTS: Covariance structure analysis showed that a
      model consisting of 23 observed indicators, 9 latent first-order factors, and one
      second-order factor fitted well and explained the structure of health behavior
      and health consciousness: the 23 items of health behavior and health
      consciousness were indicatives of the latent second-order factor named Health
      oriented Attitude. The second-order factor score was significantly higher in
      respondents willing to participate in programs of public health agencies than in
      those not willing. CONCLUSION: The results imply that reinforcement of the health
      oriented attitude may bring about improved health consciousness and practice of
      health behavior. They also suggest the necessity to reconsider traditional
      programs of public health agencies because persons with a weak health-oriented
      attitude are less likely to participate.

PMID- 17228754
TI  - [Positive effects of resistance strength training on QOL in the frail elderly].

PMID- 17228755
TI  - [Use of nutrition labels by community residents].

PMID- 17228756
TI  - [Present status of infectious keratitis].

PMID- 17228757
TI  - [Heidelberg Retina Tomograph II topographic parameters, diagnostic capabilities
      of moorfields regression analysis, and their affecting factors].
AB  - PURPOSE: To investigate optic disc topographic parameters at every stage in
      glaucoma patients and to compare results with data from normal Japanese subjects.
      We used a Heidelberg Retina Tomograph II (HRT II), to evaluate the sector
      diagnostic capabilities of Moorfields regression analysis in early glaucoma
      patients, and to determine whether there is a correlation between the background
      factors and either the topographic parameters or the diagnostic capabilities.
      SUBJECTS AND METHODS: We measured topographic parameters using HRT II, and
      examined static visual fields in 303 normal and 130 glaucoma eyes without high
      refractive error. RESULTS: Mean disc area was 2.181 +/- 0.384 mm2 in the normal
      Japanese subjects. At the time visual field loss first appeared, disc damage was
      already advanced. Moorfields regression analysis of sensitivity and specificity
      was 81.3% and 90.1%, respectively, for early glaucoma. The best diagnostic
      precision was found in the temporal/inferior sector. Correlations were noted for
      normal subject topographic parameters and the disc area, age, sex, and conus, but
      not for Moorfields regression analysis and the disc area, refractive error, age,
      and sex, even though diagnostic capabilities declined with the presence of conus.
      CONCLUSIONS: HRT II is more useful in glaucoma diagnosis than in follow-up. Focus
      should be on the temporal/inferior sector as well as on the overall Moorfields
      regression analysis. Also, close attention should be paid to the presence of
      conus.

PMID- 17228758
TI  - [Different outcome among eyes with proliferative diabetic retinopathy indicated
      for vitrectomy].
AB  - PURPOSE: The postoperative outcome was evaluated in each group of surgical
      indications of vitreous surgery for proliferative diabetic retinopathy (PDR), to
      investigate the factors responsible for postoperative visual prognosis. METHODS:
      Primary vitrectomy was performed in 119 eyes of 92 patients with PDR. Average
      postoperative follow-up period was 19 months. The indications for vitrectomy
      included vitrous hemorrhage in 58 eyes, macular tractional retinal detachment in
      17 eyes, extramacular tractional retinal detachment in 10 eyes, macular
      heterotopia in 11 eyes, and progressive fibrovascular proliferation in the
      posterior fundus in 23 eyes. RESULTS: The visual acuity finally improved by 2
      lines or more in 91 eyes (77%), remained unchanged in 10 eyes (8 %), and
      decreased by 2 lines or more in 18 eyes (15%). Final postoperative visual acuity
      was significantly better in cases of vitreous hemorrhage or progressive
      fibrovascular proliferation in the posterior fundus than in others. Preoperative
      rubeosis iridis and macular tractional retinal detachment were probably
      responsible for the final visual impairment, and intraocular tamponade affected
      the difference in visual prognosis between the groups of surgical indication.
      Multivariate analysis in all cases revealed that factors influencing visual
      outcome were preoperative rubeosis iridis and anemia. CONCLUSION: Rubeosis iridis
      and macular tractional retinal detachment were prognostic factors of the surgery.
      Vitrectomy for PDR may be effective in improving postoperative visual acuity if
      performed in the early stage of progressive fibrovascular proliferation in the
      posterior fundus after sufficient retinal photocoagulation.

PMID- 17228759
TI  - [National Surveillance of Infectious Keratitis in Japan--current status of
      isolates, patient background, and treatment].
AB  - PURPOSE: To investigate the current status of infectious keratitis in Japan.
      METHOD: Under the guidance of the Japanese Association for Ocular Infection, the
      patients with infectious keratitis caused by bacteria, fungi, or Acanthamoeba
      were surveyed at 24 facilities in Japan from January 1st, 2003, to December 31st,
      2003, concerning isolates, patient background and treatment. RESULTS: From a
      total of 261 cases, 133 micro-organisms were isolated from corneal foci of 113
      cases. There were 63 Gram-positive cocci; 42 Gram-negative bacilli; 10 Gram
      positive bacilli 4 anaerobic bacteria; 12 fungi; and 2 Acanthamoeba. Age
      distribution pattern demonstrated 2 peaks in the 20 s and in the 60 s. In the 20
      s, the percentage of contact lens users was very high (89.8%). Twenty-seven cases
      of diabetes mellitus and 10 cases of atopic dermatitis were reported as
      background systemic diseases. Levofloxacin eye drops, cefmenoxim eye drops, and
      oral or intravenous cefems were widely used as therapeutic drugs. CONCLUSION: In
      connection with contact lens usage, the occurrence of infectious keratitis in
      younger patients is marked. Gram-positive cocci are the most frequent causative
      agents.

PMID- 17228760
TI  - [Comparison of minimum inhibitory concentration and postantibiotic effect of
      eyedrops on isolates in National Surveillance of Infectious Keratitis in Japan].
AB  - PURPOSE: To determine the minimum inhibitory concentration (MIC) and
      postantibiotic effect (PAE) of antibiotic eyedrops against various isolates from
      infectious keratitis samples. METHOD: MIC and postantibiotic bactericidal effect
      (PABE)/postantibiotic fungicidal effect (PAFE) after 4 min of exposure to nine
      antibacterial eyedrops or four antifungals were examined using 100 clinical
      isolates collected by the National Surveillance of Infectious Keratitis in Japan
      in 2003. RESULT: The PABEs of tobramycin and micronomicin sulfate showed better
      results than other drugs, and the other drugs demonstrated various PABEs
      depending on the bacterial strains; in particular most drugs showed low PABE
      against Serratia marcescens. There were no significant differences between PABEs
      of methicillin-resistant and methicillin-susceptible Staphylococci. Also there
      was no statistical correlation between MIC and PABE of Staphylococci. All the
      antifungals demonstrated low PAFE against Candida spp. CONCLUSION: PABE/PAFEs
      vary among species of microorganisms, and since they have no relation with the
      usual MIC, various other factors, including species of isolates, actual clinical
      effects, and prevention of drug-resistance induction, should be considered in the
      selection of drugs.

PMID- 17228761
TI  - [Displacement of the posterior part of the eyeball in myopia].
AB  - PURPOSE: The principal aim of this study was to investigate displacement of the
      posterior part of the eyeball within the muscle cone in myopic eyes, particularly
      in moderately myopic subjects as well as in high myopes. Secondly, the
      correlation of the amount of displacement and the outer axial length of the globe
      was studied. The direction of displacement was also examined to clarify whether
      the eyeball tends to shift toward a certain direction. METHODS: Seven patients
      with moderate myopia (moderate myopia group), fifteen patients with high myopia
      without esotropia (high myopia group), five patients with high myopia and
      esotropia (myopic esotropia group), and twenty-two controls (control group) were
      examined. Using magnetic resonance imaging, the outer axial length and the
      displacement of the posterior portion of the eyeball in the muscle cone were
      measured. In order to eliminate interindividual differences in the facial
      configuration, the coronal scanning was done perpendicularly to the orbital axis.
      The displacement was measured in a plane 4 mm anterior to the globe-optic nerve
      junction. The displacement was represented by the distance and direction of the
      globe center from the center of the muscle cone. RESULTS: In the moderate myopia
      group, there was no displacement of the posterior part of the eyeball in the
      muscle cone. It was the same as in the control group. But among the three groups,
      the displacement (mean standard deviation) was significantly greater in the
      myopic esotropia group (1.53 +/- 0.49 mm) and the high myopia group (0.94 +/-
      0.52 mm) than in the control group (0.11 +/- 0.18 mm) (one way ANOVA and multiple
      comparison). The outer axial length and the distance of the displacement in all
      cases was significantly correlated (r = 0.87, p = 0.01). Moreover, the posterior
      part of the eyeball of the myopic esotropia group and the high myopia group was
      displaced superiorly and temporally. CONCLUSIONS: The posterior part of the
      eyeball of myopic eyes was displaced superotemporally in the muscle cone
      regardless of the presence of esotropia, and the amount of displacement was
      significantly correlated with the outer axial length. The more the eyeball
      expanded, the farther it was displaced. In the end, it was thought that the most
      elongated high myopic eyes would dislocate out of the muscle cone.

PMID- 17228762
TI  - [Chalcosis bulbi recognized 22 years after trauma].
AB  - PURPOSE: To report a case of chalcosis bulbi diagnosed 22 years after accidental
      entry of a foreign object into the eye. CASE: A 57 year-old woman underwent
      surgery for vitreous opacity and cataract of unknown cause. During the operation,
      an intraocular foreign body was found in the vitreous at the pars plana, and was
      removed. The object was a coated copper wire, 3.5 mm in length and 0.2 mm in
      thickness. She recalled that such a wire had accidentally entered her eye 22
      years previously. Copper particles were detected by copper staining of the
      anterior lens capsule. RESULT: Fine, sharp metal fragments may penetrate the eye
      with little resistance. When the injury results in minimal subjective symptoms,
      the person may not seek examination by an ophthalmologist. In the present case,
      the foreign body was a fragment of coated copper wire. The exposed metal surface
      was limited and the copper probably dissolved very slowly. This may account for
      the lack of significant symptoms. In the Japanese literature, there are many
      reports of coated copper wire as foreign body in the eye, but few lead to
      characteristic chalcosis bulbi.

PMID- 17228763
TI  - [Current strategies in radiation therapy for brain metastases].

PMID- 17228764
TI  - [Less invasive cistemal approach and removal of subarachnoid hematoma for the
      treatment of ruptured cerebral aneurysms].
AB  - The risk of pial or brain injury while dissecting the cerebral cistern to treat
      acute subarachnoid hemorrhage might be higher than that of unruptured aneurysms,
      because visualizing the arachnoid trabeculae between the pia mater and the
      vessels can be complicated by thick subarachnoid clots filling the cerebral
      cistern. The author describes technical points of dissecting the cerebral cistern
      and the removal of subarachnoid hematomas during acute surgical treatment for
      subarachnoid hemorrhage. Tough arachnoid trabeculae form a "perivascular cistern"
      around the relatively major vessels in both the sylvian and interhemispheric
      fissures. The cistern can be separated without pial injury by identifying the
      microstructure surrounding the major vessels in the cistern and then cutting the
      arachnoid trabeculae. After bloodless dissection of the cistern, the subarachnoid
      hematoma can easily be irrigated and removed. The subarachnoid clot must be
      repeatedly irrigated by flushing the micro-space between arachnoid trabeculae
      with jets of water to ensure efficient removal. When the arachnoid trabeculae
      become transparent, small vessels and the arachnoid trabeculae can be
      differentiated as well as whether or not they can be cut. To treat sylvian
      hematoma, subpial hematomas extending from the insular cistern and intra
      cisternal clots must be removed. Furthermore, inducing complete hemostasis by
      coagulating the subpial vessels is indispensable to prevent postoperative
      rebleeding.

PMID- 17228765
TI  - [Strategy for the treatment of incidental meningiomas].
AB  - The authors report a retrospective review o f 70 patients followed up for the
      presence of incidental, asymptomatic meningiomas. A survey was conducted of
      primary intracranial tumors diagnosed in Hiroshima Prefectural Hospital between
      1995 and 2004. The neuroradiological imaging and clinical studies for
      asymptomatic meningiomas were performed during the 57.5-month mean follow-up
      period. Of the asymptomatic 70 meningiomas, 34 (mean age 58.3yrs) were surgically
      removed just after diagnosis, whereas 36 (mean age 72.1yrs) were treated
      conservatively. There was no permanent morbidity. Five patients (13%) had the
      transient operation-related neurological morbidity, which was caused by venous
      congestion near eloquent area, or operative manipulation at the craniotomy. The
      transient morbidity in patients over 70 years was 20%, although it was 12% in
      patients under 70 years. Eight patients (21%) were complained of chronic pain at
      the wound and 5 of them had medication. In 11(30.6%) of these 36 cases treated
      conservatively, the tumor size increased by mean 0.24 cm/year. Three of them had
      operation. The tumor growth rate was 0.33 cm/year in the operative group, whereas
      it was 0.09 cm/year in the conservative group. Histological grading of 3 cases
      revealed WHO grade I meningiomas. The absence of calcification and high intensity
      on T2 weighted-imaging were significantly associated with the higher growth rate
      (p<0.05). We should decide the strategy for treatment, paying attention to the
      radiological features, the tumor growth rate, age and operative difficulty. In
      addition that, we should keep in mind that over 20% patients were suffered from
      postoperative painful wound.

PMID- 17228766
TI  - [Assessment of neurovascular compression in patients with trigeminal neuralgia
      with a boundary fusion three-dimensional magnetic resonance
      cisternogram/angiogram].
AB  - Precise assessment of the complex nerve-vessel relationship at the root entry
      zone (REZ) the trigeminal nerve is useful for the planning of the microvascular
      decompression (MVD) in patients with trigeminal neuralgia. We have applied a
      boundary imaging of fusion three-dimensional (3D) magnetic resonance (MR)
      cisternogram/angiogram. The boundary imaging allows virtual assessment of the
      spatial relationship of the neurovascular compression at the REZ of the
      trigeminal nerve. The boundary images depicted complex anatomical relationship of
      the offending vessels to the trigeminal nerve REZ. The presence of offending
      vessels, compressive site, and degree of neurovascular compression were assessed
      from various viewpoints in thl cistern and virtually through the brainstem and
      trigeminal nerve per se. The 3D visualization of the nerve-vessel relationship
      with fusion images was consistent with the intraoperative findings. The boundary
      fusion 3D MR cisternogram/angiogram may prove a useful adjunct for the diag nosis
      and decision-making process to execute the MVD in patients with trigeminal
      neuralgia.

PMID- 17228768
TI  - [A case of cavernous angioma at the septum pellucidum].
AB  - A 35-year-old female presented with a cavernous angioma of the septum pellucidum
      manifesting as headache and nausea. Computed tomography and magnetic resonance
      imaging revealed a mass at the septum pellucidum with intraventricular hemorrhage
      and mild hydrocephalus. Digital subtraction angiography showed no abnormal
      finding and thallium-201 single photon emission computed tomography showed no
      uptake in the lesion. The preoperative diagnosis was intraventricular tumor, such
      as subependymoma. The lesion was completely resected through the transcallosal
      approach. The histological diagnosis was cavernous angioma. Cavernous angiomas
      are usually located in the cerebral parenchyma and rarely occur in the cerebral
      ventricles. In particular, cavernous angioma at the septum pellucidum is very
      rare. If magnetic resonance imaging does not clearly show the typical peripheral
      hypointense rim, neuroimaging diagnosis will be difficult. Surgical resection
      should be considered to confirm the histopathology, in particular if bleeding and
      hydrocephalus are present.

PMID- 17228767
TI  - [Acute subdural hematoma associated with diffuse brain injury: analysis of 526
      cases in Japan neurotrauma data bank].
AB  - OBJECTIVE: Traumatic acute subdural hematomas (ASDH) in Japan Neurotrauma Data
      Bank were categorized into focal brain injury (FBI) group and diffuse brain
      injury (DBI) group, and were analyzed to clarify the pathophysiological and
      therapeutic aspects of these injuries. METHODS: Data in Japan Neurotrauma Data
      Bank were reviewed for 1,002 severely head-injured patients treated at hospitals
      between 1998 and 2001; 526 of these patients had ASDH. ASDH in this data bank
      were categorized into FBI group and DBI group on the findings of CT scan. The
      clinical variables in these injuries were evaluated. RESULTS: Of 526 patients
      with ASDH, 246 (46.8%) were categorized into FBI group, 280, (53.2%) were DBI
      group. The patients with DBI group were younger, injured in traffic accident,
      lower Glasgow Coma Scale (GCS), higher Injury Severity Score, poorer outcome,
      compared to those with FBI group. The patients in DBI group, who underwent
      decompressive craniectomy and craniotomy, had a significantly better outcome than
      those who underwent hematoma evacuation via burr hole. There were no relationship
      between the time from injury to operation and outcome in the patients with DBI
      group, whereas patients with early surgery in FBI group showed significantly
      poorer outcome. Hypothermia and the placement of intracranial pressure monitor
      improved outcome only in patients of DBI group. CONCLUSION: It seems that the
      pathophysiological and therapeutic aspects of ASDH associated with DBI might
      differ from that with FBI alone.

PMID- 17228769
TI  - [A case of infected subdural hematoma].
AB  - A 87-year old male was admitted to our hospital due to generalized convulsion
      with loss of consiousness. He was afebrile and his blood sampling was not
      infectious. Computed tomography scan suspected left chronic subdural hematoma.
      Burr hole drainage was performed to remove the hematoma, but the abscess was
      aspirated in the subdural space. Infected subdural hematoma is rare. We discuss
      the clinical presentation, diagnosis and. treatment, and also briefly review the
      literature.

PMID- 17228770
TI  - [Spontaneous closure of dural arteriovenous fistula after performing diagnostic
      angiography].
AB  - The pathogenesis and clinical treatment of dural arteriovenous fistulas (DAVF)
      has been well established. However, only 15 cases of spontaneous closure of DAVFs
      have been reported. We describe a case of spontaneous closure of a DAVF. A 60
      year-old male presented with pulsatile tinnitus. Selective cerebral angiography
      revealed a left posterior DAVF fed by the left occipital artery and the middle
      meningeal artery, which drained into the left transverse sinus and sigmoid sinus.
      Following the initial angiography, the patient exhibited vomiting with transient
      disorientation and amnesia. These symptoms, along with the tinnitus, disappeared
      by the following day. Seven days after the initial angiography, a second
      angiography was performed that revealed the complete disappearance of the DAVF.
      Previous reports have described a long period of closure for DAVFs following
      initial diagnosis. Possible mechanisms for spontaneous closure of DAVFs include
      the development of scar tissue or a sinus thrombosis that leads to occlusion of
      the DAVF In this case, the DAVF closure may have been due to a sinus thrombosis
      induced by sinus stenosis, since occlusion of the draining sinuses coincided with
      the spontaneous closure of the DAVF. In cases of non-traumatic DAVF without
      cortical venous reflex that do not present severe symptoms, a prudent course of
      treatment is necessary since there is a chance of spontaneous closure of the DAVF
      occuring.

PMID- 17228771
TI  - [A case of nasal dermal sinus-cyst (NDSC) with intracranial extension].
AB  - Nasal dermal sinus-cyst (NDSC) is a rare abnormality consisting of a dermal sinus
      opening at the nasal skin and dermoid cyst localized in the frontobasal area. A 2
      year-old boy was admitted to our hospital due to swelling of the fronto-nasal
      regions with pus running from an orifice situated in the nasal skin. Bone-image
      CT and 3D-CT revealed bone defects within the frontal skull base. MRI
      demonstrated that a dermoid cyst centered in a bone defect was in contact with
      the dura of the frontobasal area, and a dermal sinus extending to the frontonasal
      skin could also be detected. Surgical resection was performed by frontobasal
      craniotomy. The dermal sinus was followed subcutaneously into the orifice of the
      nasal skin. A small skin incision was made and the sinus was then totally
      removed. The authors describe in detail this case of NDSC which extended to the
      intracranium, and review the literature regarding this abnormality.

PMID- 17228772
TI  - [Retroodontoid mass without atlantoaxial subluxation in an elderly patient: case
      report].
AB  - A Mass at the craniovertebral junction is relatively rare. We report a case of
      retroodontoid mass without atlantoaxial subluxation. An 84-year-old female
      presented to our hospital with paresthesia in the right upper and lower limb. She
      had no history of head or spine injury. Neurological examination revealed slight
      motor weakness of the right upper and lower limb. Cervical radiographs showed
      osteoarthrosis without atlantoaxial subluxation. MRI revealed retroodontoid,
      extra-dural mass that severely compressed the adjacent spinal cord. The patient
      underwent C1 laminectomy and posterior C1-C2 fusion with polyaxial screw and rod
      fixation. Simultaneously, the mass was resected partially. Histopathologically,
      the surgical specimen was a non-neoplastic fibrocartliginous mass and
      inflammatory cells were not seen. Postoperative course was uneventful and her
      neurological condition gradually improved. MRI revealed marked reduction of the
      mass and improvement of the spinal cord compression six months after the
      operation. We discuss the genesis of the retroodontoid mass and the strategy for
      surgical treatment.

PMID- 17228773
TI  - [Information guided technology and procedure in neurosurgical field].
AB  - Translational Research is the research to apply and mediate a fundamental
      research result to the clinical field effectively. The integration of the
      diagnosis and the treatment is an important item in the life science field from
      the viewpoint of quality of therapy and minimally invasive therapy. The
      standardization of mechanical interface of the medicine related machine, system
      and a medical information system are important from the viewpoint such as
      prevention of medical malpractice. A high function operating robot (manipulator)
      as an endoscopic robot and image-guided minimally invasive device are important
      in the point of view of the development of a medical device shown with a medical
      device industry vision. We describe an outline of our ongoing development of
      endoscope system, intraoperative MRI (intelligent operating theater) and robot
      surgery system in neurosurgical field.

PMID- 17228775
TI  - [Neuropsychological approach to visual attention].
AB  - Visual experience depends critically on visual attention, which selects a
      particular aspect of a visual display. Recent clinical, neuroimaging, and animal
      studies revealed that visual attention was divided into active and passive or top
      down and bottom-up attention. Although these dichotomies are clear-cut in
      definition, visual attention could be modulated by many factors. Detailed
      observation of brain-injured patients provides with evidence for dynamic and fine
      control of visual attention. We observed patients with dorsal simultanagnosia and
      that with callosal disconnection syndrome. Patients with dorsal simultanagnosia
      demonstrated that extent of visual attention was dynamically changed depending on
      the level of visual processing. Despite the ability to read a kanji character and
      to describe its components correctly, a patient could not notice a component that
      he had just written and could not assemble individual components to make up a
      correct kanji character. He could point to an overlapping area of two figures.
      But once he started to color the overlapping area, he missed the margin of the
      area and colored much larger area. Another patient with dorsal simultanagnosia
      missed borderlines between columns of a newspaper and read letters continuously
      across columns. In contrast, he could point to lines between figures or
      meaningless patterns easily. These findings indicated that visual attention was
      directed automatically to meaningful characters. A patients with callosal
      disconnection syndrome demonstrated left unilateral spatial neglect only when he
      used his right hand to draw figures. Right hand movement, controlled by the left
      hemisphere, elicited visual attention to the right hemispace, resulting in the
      left unilateral spatial neglect. Thus visual attention is not simply top-down or
      bottom up, but is implicitly affected by the visual recognition as well as motor
      component of the task.

PMID- 17228774
TI  - [Roundtable discussion: advances in neuroscience and therapeutic research on
      neurological diseases--the present status and future prospects].

PMID- 17228777
TI  - [Parallel processing of motion vision].
AB  - Several neuropsychological studies have reported dissociation between motion
      vision and object vision. One patient with motion blindness had a bilateral MT/V5
      lesion and could see objects, but could not see the motion of the objects (Zihl
      et al, 1983). By contrast, some blindsight patients with primary visual cortex
      lesions cannot see objects but can see their movement (e.g. Riddoch, 1917). These
      results imply that movement vision and form vision rely on independent
      mechanisms. However one patient with motion blindness had controversial symptoms
      concerning motion vision. She could not perceive the movement of objects,
      although she could walk without colliding with obstacles and could catch incoming
      objects. It has also been reported that patients with a bilateral parietal lesion
      had well-preserved primary motion vision, but had problems walking and catching a
      ball (Vaina, 1998). Therefore, motion for vision and motion for action might have
      independent mechanisms. Such dissociation has also been noted in patients with
      Balint syndrome. Some patients behave like a blind person but can walk and catch
      a ball, while other patients bump into obstacles while walking. These results
      indicate that the neural bases of motion vision are distinct from those of form
      vision and that there are subdivisions of motion vision.

PMID- 17228776
TI  - [Neural mechanisms for object and color recognition].
AB  - We reported double-dissociation between the visual processing of the edges and
      the surfaces of objects. Patients with lateral occipital damage showed selective
      impairment in the perception of edges whereas those with medial ventral occipital
      damage showed selective impairment in the perception of the 3D structure of the
      surface. Patients with medial ventral occipital damage also exhibited impaired
      perception of color, which is also a surface property. Those results were
      consistent with those from neuroimaging studies. Taken together, those studies
      suggest that objects may be processed in two separate pathways in the ventral
      occipital cortex: the edges of objects are processed in the lateral pathway and
      the surface of objects are processed in the medial pathway. Both edges and
      surfaces play important roles in object recognition, and both types of perception
      should be evaluated in patients with visual agnosia.

PMID- 17228778
TI  - [Neural mechanisms of facial recognition].
AB  - We review recent researches in neural mechanisms of facial recognition in the
      light of three aspects: facial discrimination and identification, recognition of
      facial expressions, and face perception in itself. First, it has been
      demonstrated that the fusiform gyrus has a main role of facial discrimination and
      identification. However, whether the FFA (fusiform face area) is really a special
      area for facial processing or not is controversial; some researchers insist that
      the FFA is related to 'becoming an expert' for some kinds of visual objects,
      including faces. Neural mechanisms of prosopagnosia would be deeply concerned to
      this issue. Second, the amygdala seems to be very concerned to recognition of
      facial expressions, especially fear. The amygdala, connected with the superior
      temporal sulcus and the orbitofrontal cortex, appears to operate the cortical
      function. The amygdala and the superior temporal sulcus are related to gaze
      recognition, which explains why a patient with bilateral amygdala damage could
      not recognize only a fear expression; the information from eyes is necessary for
      fear recognition. Finally, even a newborn infant can recognize a face as a face,
      which is congruent with the innate hypothesis of facial recognition. Some
      researchers speculate that the neural basis of such face perception is the
      subcortical network, comprised of the amygdala, the superior colliculus, and the
      pulvinar. This network would relate to covert recognition that prosopagnosic
      patients have.

PMID- 17228779
TI  - [Prevention of brain infarction in patients with atrial fibrillation].
AB  - The patients with cardioembolic stroke sometimes suffer from severe neurological
      deficit and from recurrent strokes. Since atrial fibrillation, especially non
      valvular atrial fibrillation (NVAF) is associated with over half of the
      cardioembolic strokes, the prevention of cardioembolic stroke in patients with
      NVAF is important. There have been some reports about how to prevent stroke. They
      have indicated that the best medication for preventing from stroke was
      anticoagulation by warfarin. Therefore, the guidelines recommended the patients
      with NVAF to take warfarin. In case with the older patients under 70 years,
      prothrombin international normalized ratio (PT-INR) should be kept from 2.0 to
      3.0. On the other hand, if the patients with NVAF are over 70 years, PT-INR has
      to be controlled from 1.6 to 2.6. Before extraction of a tooth, anticoagulation
      should not be call off.

PMID- 17228780
TI  - [Adult-onset citrullinemia].
AB  - Adult-onset citrullinemia (CTLN2) is a rare hereditary metabolic disorder
      characterized by highly increased concentration of citrulline and ammonia in the
      plasma, which is ascribed to a deficiency of argininosuccinate synthetase (ASS),
      one of the urea cycle enzymes mainly located in the liver. Neurological
      manifestation in CTLN2 patients closely resemble those of hepatic encephalopathy
      and in the past, most patients usually followed rapidly deteriorating clinical
      courses and died of severe brain edema within a few years after onset. However,
      in 1995 the first CTLN2 patient who was successfully treated by living-related
      liver transplantation was reported and since then more than 30 patients had
      underwent this operation in our country, showing good outcomes. No primary defect
      had not been found within ASS gene locus, but the causative gene of this disorder
      is now identified as the "citrin gene", which might act as a aspartate/glutamate
      transporter in mitochondria. Different phenotypes are seen in the individuals
      with a citrin deficiency: neonatal intrahepatic cholestasis, juvenile-onset
      chronic pancreatitis and hepatocellular carcinoma without cirrhosis can precede
      the appearance of CTLN2. The precise pathogenesis of this disease that includes
      the relationship between the mutations of citrin gene and a deficiency of hepatic
      ASS activity remains unclear.

PMID- 17228781
TI  - [Development of the Telephone Interview for Cognitive Status (TICS) in Japanese].
AB  - In recent years, population of elder people has increased in Japan, following
      augmentation of the number of people with dementia in Japan. Then it is important
      to detect cognitive impairment in early stage for adequate treatment, care and
      prevention. We studied 135 subjects, 49 patients with Alzheimer's disease (AD)
      and 86 healthy controls using Telephone Interview for Cognitive Status (TICS),
      and developing Japanese version of the TICS (TICS-J). The sensitivity and the
      specificity of the TICS-J to differentiate AD patients from healthy controls was
      98.0% and 90.7%, respectively. Pearson's correlation coefficiency between the
      TICS-J and Mini-Mental State Examination (MMSE) was 0.858 (p < 0.001). On the
      receiver operating curves, the area under the curve for the TICS-J was 98.7% (95%
      CI: 97.5%-100%). These results indicate that TICS-J is sensitive and specific
      instrument for differentiating AD patients from healthy controls.

PMID- 17228782
TI  - [Case of ruptured superior cerebellar artery dissection treated by endovascular
      embolization].
AB  - The authors herein report a case of a ruptured dissection of the superior
      cerebellar artery (SCA). A 68-year-old man presented with symptons of sudden
      headache and nausea. The CT scan revealed the presence of both a subarachnoid
      hemorrhage (SAH) and acute hydrocephalus. The left vertebral angiogram showed an
      fusiform dilatation in the cerebellomesencephalic segment of the left SCA.
      Endovascular embolization of the aneurysm and SCA was successfully performed
      using Guglielmi detachable coils (GDCs). No delayed ischemic deficits were
      observed after the treatment. A dissection of the distal segment of the SCA is a
      very rare occurrence. We believe endovascular embolization using GDCs to be an
      effective and less invasive therapy for the treatment of an SCA dissection with
      SAH.

PMID- 17228783
TI  - [Autopsied case of 89-year-old female who was complicated with dementia 14 years
      from the onset of spastic gait in her total 27 years of clinical course (clinical
      conference)].

PMID- 17228784
TI  - [Present status in and future prospects for development of protein function
      inhibitors for gynecologic neoplasms].

PMID- 17228785
TI  - [Evaluation of physician-patient communication in medical disputes].

PMID- 17228786
TI  - [Clinical studies of pediatric malabsorption syndromes].
AB  - Multiple cases with various types of pediatric malabsorption syndromes were
      evaluated. The clinical manifestations, laboratory findings, pathophysiology, and
      histopathological descriptions of each patient were analyzed in an effort to
      clear the pathogenesis of the malabsorption syndromes and the treatments were
      undertaken. The cases studied, included one patient with cystic fibrosis, two
      with lactose intolerance with lactosuria (Durand type), one with primary
      intestinal lymphangiectasia, two with familial hypobetalipoproteinemia, one with
      Hartnup disease, one with congenital chroride diarrhea, one with acrodermatitis
      enteropathica, one with intestinal nodular lymphoid hyperplasia (NLH), five with
      intractable diarrhea of early infancy and four with glycogenosis type Ia. Each
      case description and outcome is described below: 1. A 15-year-old Japanese boy
      with cystic fibrosis presented with severe symptoms, including pancreatic
      insufficiency, bronchiectasis, pneumothorax and hemoptysis. His prognosis was
      poor. Analysis of the CFTR genes of this patient revealed a homozygous large
      deletion from intron 16 to 17b. 2. In the sibling case of Durand type lactose
      intolerance, the subjects'disaccaridase activity of the small bowel, including
      lactase, were within normal limits. The results of per oral and per intraduodenal
      lactose tolerance tests confirmed lactosuria in both. These observations
      suggested, not only an abnormal gastric condition, but also duodenal and
      intestinal mucosal abnormal permeability of lactose. 3. In the case of primary
      intestinal lymphangiectasia, the subject had a lymphedematous right arm and hand,
      a grossly coarsened mucosal pattern of the upper gastrointestinal tract
      (identified via radiologic examination) and the presence of lymphangiectasia
      (confirmed via duodenal mucosal biopsy). The major laboratory findings were
      hypoalbuminemia, decreased immunoglobulin levels and lymphopenia resulting from
      loss of lymph fluid and protein into the gastro-intestinal tract. 4. In two cases
      of heterozygous familial hypobetalipoproteinemia, serum total cholesterol and
      betalipoprotein levels were very low. The subjects presented with symptoms and
      signs of acanthocytosis and fat malabsorption. Further, one subject had
      neurological abnormalities such as mental retardation and severe convulsions.
      Treatment with MCT formula diet corrected the lipid malabsorption. 5. A 5-year
      old girl presented with pellagra-like rashes, mental retardation and cerebellar
      ataxia. An oral tryptophan (Trp) and dipeptide (Trp-Phe) loading test were
      conducted and the renal clearance of amino acids was also evaluated in this
      patient and in controls. Following the oral Trp loading test, plasma levels of
      Trp indicated a lower peak in the case, reaching a maximum at 60 minutes. On the
      other hand, the oral dipeptide (Trp-Phe) loading test in the Hartnup patient
      showed the peak Trp plasma level was the same as the control subjects. The renal
      clearance of neutral amino acids in this case increased to levels 5 to 35 times
      normal. 6. In the case of congenital chloride diarrhea, the subject had secondary
      lactose intolerance, dehydration, hyponatremia, hypokalemia, hypochloremia,
      hyperreninemia and metabolic alkalosis. The chloride content of her fecal fluid
      was very high. The concentrations were 89-103 mEq/l. In contrast, her urine was
      chloride-free. The subject's growth and development improved after treatment with
      lactose free formura and oral replacement of the fecal loses of water, NaCl and
      KCl. Unfortunately, the patient died of a small bowel intussusception. The kidney
      histopathological finding was juxtaglomerular hyperplasia by a necropsy. 7. In
      the case of acrodermatitis enteropathica, the subject had characteristic skin
      lesions, low serum zinc levels and ALPase activity. An oral ZnSO4 loading test
      and intestinal mucosal histology by a peroral biopsy were conducted. The serum
      zinc peak level was 2 hours after the oral ZnSO4 loading test. Infant formula
      alone could not maintain normal serum zinc ranges. Light microscopic studies of
      the intestinal villous architecture showed a normal pattern. However,
      ultrastructual examination of several epithelial cells revealed numerous
      intracellular vesicles. After zinc therapy, these changes were decreased. The
      lesions were postulated as the secondary result of zinc deficiency. 8. A 12-year
      old girl presented with hypogammaglobulinemia, recurrent infections, chronic
      diarrhea and intestinal NLH. A barium meal and follow-through examination showed
      multiple nodules throughout the stomach and intestine. The nodules, all uniform
      in size, were 2 mm diameter. The barium enema did not show NLH in the colon.
      Mucosal biopsy of the stomach and jejunum revealed the typical histology of NLH
      in the lamina propria. Also, achlorhydria was present in this patient and her
      serum gastrin levels were very high; 315-775 pg/ml. 9. In 4 cases of intractable
      diarrhea in early infancy (by Avery G B), a jejunal biopsy showed shortening
      villi and nonspecific enterocolitis. Some patients were found with only low
      lactase or low lactase and sucrase levels. An electron microscope analysis of the
      small bowel in 2 cases showed alterations: increased pinocytosis in microvillus
      membranes and lysosomes by endocytosis of undigested macromolecular substances. I
      postulated that the stated evidence was causative of this clinical profile. 10. I
      frequently observed diarrhea as a clinical manifestation in glycogenosis type Ia
      and lipid malabsorption in one case. The light and electron photomicrographs
      showed intestinal absorption cells with the glycogen deposits in the inferior
      devision of nuclei.

PMID- 17228787
TI  - [Determination of epoxidized soybean oil in bottled foods].
AB  - A determination method for epoxidized soybean oil (ESBO) in bottled foods was
      developed and used to survey bottled foods on the Japanese market. The amount of
      sample required was decreased to 20 g and the standard addition method was
      adopted for the quantification, because lipid in foods interrupted the hydrolysis
      of ESBO. The recoveries were 87.1 and 98.9% and the determination limit was 5.0
      microg/g for a 20 g sample, be cause lipid in foods interupted the hydrolysis of
      ESBO. The recoveries using the internal standard method varied widely, because
      hydrolysis of the internal standard, cis-11,14-eicosadienoic acid ethyl ester,
      was affected more than that of ESBO by coexisting lipid in the sample. ESBO was
      not detected in any of the bottled baby food samples examined (14 samples),
      though it had been frequently detected in previous European surveys. This
      difference may be related to the low fat content and low fluidity of the bottled
      baby foods retailed in Japan. On the other hand, ESBO was detected at levels of
      25.7-494.0 microg/g in liver paste, pasta sauce, Sungan in spicy oil, and spicy
      oil. These foods had higher fat content and higher fluidity. However, ESBO intake
      from these foods appears unlikely to exceed the TDI in the EU (1 mg/kg bw/day).

PMID- 17228788
TI  - [Concentration in plasma and excretion in milk of lactating cows after oral
      administration of tribromsalan, oxyclozanide and bromofenofos].
AB  - The fasciolicides tribromsalan (TBS), oxyclozanide (OCZ) and bromofenofos (BFF)
      were orally administered to three lactating cows. The concentrations of TBS, OCZ
      and the BFF metabolite dephosphate bromofenofos (DBFF) in plasma, and the
      excretion of these compounds in milk were determined by high-performance liquid
      chromatography. In plasma, the concentrations of TBS, OCZ and DBFF reached
      maximum at about 1.0 day and the compounds remained detectable until 5.7, 7.4 and
      15.1 days after administration, respectively. The detection limits of these
      compounds in plasma were 10, 2 and 2 ppb, respectively. In milk, the
      concentrations of TBS, OCZ and DBFF reached maximum at about 24 hours and the
      compounds remained detectable until 30-47, 30-47 and 78-119 hours after
      administration, respectively. The detection limits of these compounds in milk
      were 5.1 and 1 ppb, respectively. The residence times of TBS and BFF were very
      close to the withdrawal times of the fasciolicides.

PMID- 17228789
TI  - [Determination of glycarbylamide based on formation of nickel chelate].
AB  - A new and simple analytical method for glycarbylamide (GB) based on the formation
      of nickel chelate was developed. The proposed method is as follows: sample
      solution is mixed with 0.08 mmol/L nickel nitrate in 0.2 mol/L carbonate buffer
      (pH 9.0), and the absorbance is measured at 290 nm. Under the optimal conditions,
      GB could be determined in the concentration range from 0.13 microg/mL to 2.6
      microg/mL (r = 0.9999). Using this method for HPLC post column reaction, GB
      levels in chicken liver extracts could be determined. The recovery of GB was
      79.4% (RSD=2.6%, n=3) and the quantitation limit was 30 ng/g. The apparent molar
      extinction coefficient (epsilon) of the GB-nickel complex was 8.5 x 10(3). The
      molar ratio of the complex is GB: nickel ion = 2:1.

PMID- 17228790
TI  - [Residue analysis of metoclopramide in bovine and swine tissues by HPLC and
      administration experiment].
AB  - A reversed-phase ion-pair HPLC method with ultraviolet detection has been
      developed for determination of metoclopramide (MCP) in bovine and swine muscle,
      liver, kidney, fat and intestine. MCP was extracted from samples with
      acetonitrile, and the extracts were cleaned up on an Oasis HLB cartridge (60 mg)
      after liquid-liquid extraction. The limit of detection of MCP was 0.002 microg/g
      and the limit of quantitation was 0.007 microg/g. Recoveries of MCP spiked at
      0.03 ppm ranged from 74.1 to 93.3% for bovine tissues and from 86.1 to 92.7% for
      swine tissues. The present method was used for the analysis of bovine and swine
      tissues 1 day after withdrawal following drug administration. The MCP
      concentrations in all tissues were lower than the Japanese provisional MRLs.

PMID- 17228791
TI  - [Detection of short tandem repeat (STR) polymorphisms by microchip
      electrophoresis for individual identification of cattle].
AB  - A simple and rapid detection of short tandem repeat (STR) markers was studied as
      a screening test for individual identification of cattle. DNAs were extracted
      from eight commercial beef samples by a proteinase K-boil method followed by
      purification with 2-propanol precipitation. Five STR markers, known to be highly
      polymorphic, were amplified by PCR and analyzed both by a conventional sequencing
      analysis (SEQ) and by a proposed microchip electrophoresis (MEP). Every marker
      revealed high polymorphism, such as 5-9 alleles in SEQ analysis, and 4-6 alleles
      in MEP analysis. This simple and rapid MEP analysis is expected to be an
      effective screening tool with use of confirmatory SEQ analysis.

PMID- 17228792
TI  - [Identification of fungi using DNA sequences: an approach to identify Fusarium
      species isolated from domestic unpolished rice].
AB  - Molecular approaches are being developed to provide for the rapid and objective
      identification of fungi. We attempted the identification of Fusarium species by a
      genetic analysis to validate practically the utility of a molecular approach for
      fungal identification and to reveal its limitations, and sequenced three regions,
      the 5' end of the 28S rRNA gene (D2 region) and the internal transcribed spacer 1
      and 2 (ITS1 and ITS2) regions, in the rRNA genes. The DNA sequences of 38
      Fusarium strains isolated from domestic unpolished rice were compared for
      similarity with entries in the GenBank. Based on this comparison, it was
      estimated that all these three regions, as a minimum, must be compared with the
      database to identify Fusaria at the species level. According to the combinations
      of sequences in the three regions, the 38 isolates were classified into 13
      groups. Out of the 13 groups, 6 groups (20 isolates in total) could be identified
      as definite species based only on the sequence data. For the other 6 groups (17
      isolates in total), candidate species were limited on the basis of the sequence
      similarity, and then the isolates were identified at the species level with the
      aid of morphology. Only one isolate could not be identified. These results
      verified that DNA sequence comparison with the GenBank database is useful for the
      identification of Fusarium species.

PMID- 17228793
TI  - [Analysis of tetracyclines in honey and royal jelly by LC/MS/MS].
AB  - A simple and accurate method using liquid chromatography coupled with tandem mass
      spectrometry (LC/MS/MS) was developed for the determination of tetracyclines
      (TCs), i.e., oxytetracycline (OTC), chlortetracycline (CTC) and tetracycline
      (TC), in honey and royal jelly. Mass spectral acquisition was performed in the
      positive mode. In LC separation, L-column ODS and 0.01% formic acid-acetonitrile
      were used as the column and mobile phase, respectively. TCs in a honey sample
      were diluted with water, while TCs in royal jelly were extracted with 2%
      metaphosphoric acid-methanol (6:4). They were cleaned up with Oasis HLB and Sep
      Pak C18 cartridges, respectively. The quantification limits of TC, OTC, and CTC
      were 5, 5, and 10 ng/g, respectively, while those in royal jelly were 25, 25, and
      50 ng/g, respectively. The recoveries of TCs from both honey and royal jelly were
      75-120%.

PMID- 17228795
TI  - [Development of a predictive program for microbial growth under various
      temperature conditions].
AB  - A predictive program for microbial growth under various temperature conditions
      was developed with a mathematical model. The model was a new logistic model
      recently developed by us. The program predicts Escherichia coli growth in broth,
      Staphylococcus aureus growth and its enterotoxin production in milk, and Vibrio
      parahaemolyticus growth in broth at various temperature patterns. The program,
      which was built with Microsoft Excel (Visual Basic Application), is user
      friendly; users can easily input the temperature history of a test food and
      obtain the prediction instantly on the computer screen. The predicted growth and
      toxin production can be important indices to determine whether a food is
      microbiologically safe or not. This program should be a useful tool to confirm
      the microbial safety of commercial foods.

PMID- 17228794
TI  - Inhibitory effects of acidic xylooligosaccharide on stress-induced gastric
      inflammation in mice.
AB  - The preventive effects of acidic xylooligosaccharide prepared from xylan of
      corncobs and related sugars on stress-induced gastric inflammation in mice were
      investigated. Oral administration of acidic xylooligosaccharide and
      hydrocortisone at doses of 100 and 200 mg/kg body weight significantly reduced
      the number of bleeding points in the gastric mucosa of mice loaded with cold
      restraint stress. Acidic xylooligosaccharide showed concentration-dependent
      superoxide anion radical-scavenging activity at concentrations of 3.3-4.3 mg/mL
      and its IC50 was 3.5 mg/mL, although this value is approximately six times that
      of quercetin. The antioxidant activity of acidic xylooligosaccharide could
      contribute, in part, to its suppressive activities on stress-induced mouse
      gastritis. Xylose, xylobiose, xylan, and glucuronic acid showed no significant
      suppressive activities on mouse gastric inflammation at a dose of 100 mg/kg body
      weight. These results suggest that an appropriate degree of polymerization of
      xylan (larger than trimer) is necessary for the activities of acidic
      xylooligosaccharide.

PMID- 17228796
TI  - [Determination of glycarbylamide residues in chicken tissues by HPLC with post
      column reaction].
AB  - A newly developed HPLC method for determination of glycarbylamide (GB) in chicken
      liver was applied to other tissues (muscle, fat and kidney). The recoveries of GB
      in muscle, fat and kidney were 87.2% (CV 0.5), 91.3% (CV 4.7), 79.7% (CV 1.0),
      respectively. The detection limit of GB was 0.01 ppm. GB concentrations were
      determined by this method in tissues (muscle, fat, liver and kidney) from
      chickens sacrificed 5 days after oral administration of GB mixed in feed at 60
      mg/kg of feed for 7 days. GB was not detected in these chicken tissues.

PMID- 17228797
TI  - [Survey on the quality of commercial Nigari (crude magnesium chloride [sea
      water])].
AB  - Contents of minerals (Mg, Ca, Na and K), anions (SO4(2-), Br- and Cl) and heavy
      metals (Pb, Cd, Zn, Hg and As) were determined in 17 commercial samples of
      Nigari, 15 samples of crude magnesium chloride (sea water) products as a food
      additive and 2 magnesium-containing foods. Obtained values were compared with the
      specifications proposed in a draft of the eighth edition of Japan's
      Specifications and Standards for Food Additives. Out of 15 food additive samples,
      only 5 samples satisfied the specification. Since the Joint FAO/WHO Expert
      Committee on Food Additives (JECFA) proposed to lower the limits of heavy metals
      in food additives, a simple method was developed for the determination of low
      levels of Pb and Cd by extracting chelates of these metals with organic solvents.
      The quantification limits for Pb and Cd were 0.5 microg/g and 0.05 microg/g,
      respectively. It was estimated from the SO4(2-)/Ca ratios that 15 samples were
      sea water evaporation products, and the remaining 2 were ion-exchange membrane
      process products. No pollution with heavy metals was found in any of the samples.

PMID- 17228798
TI  - [Scombroid fish poisoning due to histamine-producing bacteria].

PMID- 17228799
TI  - [Use of pesticide analysis in foods with emphasis on supercritical fluid
      extraction (SFE)].

PMID- 17228800
TI  - [Points to keep in mind when using ELISA kits for food allergen screening].

PMID- 17228801
TI  - [Bacteriological and pathological analysis on the pathogenetic factors for
      cavitary and nodular bronchiectatic type of pulmonary Mycobacterium avium
      intracellulare complex disease].
AB  - A total of 101 strains of Mycobacterium avium complex (MAC), consisting of 86 M.
      avium and 15 M. intracellulare strains, were examined by DNA sequencing. The
      frequency of radiological types [cavitary (Cav) type and nodular bronchiectatic
      (NB) type] was similar in each species, thus, both species are equal causes of
      the two radiological types of MAC disease. We also examined serovars of the
      isolated strains using extracted glycopeptidelipid antigens and thin layer
      chromatography. Cav type patients discharged a single serovar MAC, while NB type
      patients discharged two serovar MACs simultaneously. RFLP pattern obtained by the
      use of IS1245, revealed no clustering of the strains specific for Cav type and NB
      type. Histopathological examinations of the bronchial lesions in 40 MAC cases and
      49 multi-drug resistant tuberculosis (MDR-TB) cases were performed on the
      surgically removed lung specimens. Lymphocytic infiltration, epithelioid cell
      granuloma formation, epithelial desquamation and ulceration, as well as smooth
      muscle atrophy as a cause of bronchiolectasis, were observed more often and were
      more severe in the peripheral bronchial walls of the NB type than the Cav type of
      MAC, and as compared with those of MDR-TB cases.

PMID- 17228802
TI  - [The stady of pulmonary hypertension and plasma BNP values in respiratory
      diseases].
AB  - We measured plasma BNP and hANP levels and studied the relationship to
      echocardiographic findings in 49 patients who visited or admitted in our hospital
      due to dyspnea (25 with chronic obstructive pulmonary disease (COPD), 8 with
      interstitial pneumonia, 16 with sequelae of tuberculosis). The age in the
      interstitial pneumonia group was lower and the arterial blood partial pressure of
      CO2 was higher in the sequelae of tuberculosis group. Plasma BNP and hANP levels
      were similar in the three groups. Plasma BNP level did not correlate with the
      pressure gradient measured from tricuspid valve regurgitation. Some patients had
      pulmonary hypertension despite having low plasma BNP levels. Hypoxemia was more
      severe in the higher BNP level group than in the lower BNP level group. Plasma
      BNP levels did not reflect pulmonary hypertension unless these was left
      ventricular failure or valvular diseases in these groups.

PMID- 17228803
TI  - [A case of follicular bronchiolitis preceding rheumatoid arthritis].
AB  - A 52-year-old woman was admitted to Yame General Hospital because of persistent
      cough, wheeze, and shortness of breath at age 48. Chest X-ray and computed
      tomography (CT) showed bilateral centrilobular shadows. Pulmonary function test
      revealed obstructive dysfunction. She also had chronic sinusitis. Initially,
      diffuse panbronchiolitis was diagnosed and she was given macrolides, but no
      improvement was observed. Thus video-assisted thoracoscopic lung biopsy (VATS)
      was performed in order to establish a definitive diagnosis. Histopathological
      findings were compatible with a diagnosis of follicular bronchiolitis. Treatment
      with corticosteroid (oral prednisolone, 50 mg/day) improved her condition.
      However, on reducing the steroid doze, her symptoms and chest X-ray film/CT
      findings became exacerbated. In addition, polyarthritis appeared. Further
      investigations revealed a diagnosis of rheumatoid arthritis. Only 2 cases of
      follicular bronchiolitis preceding rheumatoid arthritis have been reported in
      Japan.

PMID- 17228804
TI  - [A case of Behcet disease with multiple nodular shadows and aneurysm of the
      brachiocephalic trunk caused by necrotizing vasculitis].
AB  - A 36-year-old man was admitted to our hospital in 1994 because of fever, and
      abdominal CT showed multiple low-density areas in the liver. Although granulomas
      were found in a liver biopsy specimen, a definitive diagnosis could not be
      established. With complaints of oral and genital ulcerations and erythema
      nodosum, Behcet disease was diagnosed in 1995 and he was treated with colchicine
      and cyclosporin. In May 1997 he had fever, leg edema, and proteinuria, and a
      renal biopsy revealed secondary amyloidosis. Cavitary lesions were found on a
      chest X-ray for the first time, but these later disappeared spontaneously. In
      October 2002, nodular shadows, cavitary lesions, and a mediastinal tumor appeared
      on a chest X-ray film. The nodular shadows in the lung fields had transformed
      into cavity lesions, resulting in the disappearance of the shadows. Specimens
      obtained from an open lung biopsy showed necrotizing granulomas and destructive
      vasculitis of the lung, and aneurysm of the brachiocephalic trunk caused by
      destructive vasculitis. Because multiple nodular shadows with cavitary lesions in
      Behcet disease, as in this case, have never been reported, we think this is a
      rare case.

PMID- 17228805
TI  - [A case of pyothorax caused by Mycobacterium avium].
AB  - A 74-year-old woman was admitted to our hospital in December, 2003 because of
      anorexia and weight loss lasting from August, 2003. Chest CT scan showed empyema
      with a niveau in the right lung and infiltrative and nodular shadows in the left
      lung. Acid-fast bacilli were detected in pleural effusion. Polymerase chain
      reaction (PCR) test was negative for Mycobacterium tuberculosis (M. tuberculosis)
      but positive for Mycobacterium avium (M. avium). PCR test for M. avium was also
      positive in bronchial lavage fluid, and many colonies of M. avium complex ( MAC)
      were cultured from pleural effusion. After we administered 4 drugs including RFP,
      EB, SM, and CAM, cultured colonies of M. avium decreased, the inflammatory
      reaction improved, and infiltrates in the left upper lobe has disappeared. These
      improvements confirmed the diagnosis of empyema caused by M. avium. Since
      nontuberculous mycobacteria induced empyema has rarely been reported, the
      clinical features of this disease should further be examined.

PMID- 17228806
TI  - [A case of severe airflow limitation markedly improved by inhalation therapy in
      non-smoking woman with chronic obstructive pulmonary disease].
AB  - A 67-year old woman who had never smoked presented with dyspnea on effort and
      general fatigue, which had first appeared 4 years ago. She had lived for 35 years
      with her husband who was a heavy smoker. Chest roentgenogram showed pulmonary
      over-inflation, but chest CT scans didn't demonstrate emphysematous changes.
      Neutrophil-dominant sputum cytology, a PaO2 of 69.5 Torr, and combined
      ventilatory impairment on respiratory function test were revealed. FEV1.0
      improved 80 ml after beta2-agonist inhalation. Although the respiratory symptoms
      were improved by inhaled anti-cholinergic drug, residual volume increased
      minimally. After the use of inhaled steroid drug (HFA-BDP) and salmeterol, the
      symptoms and residual volume were markedly improved. One year later, FEV1.0
      increased by 450 ml. The low attenuation area detected by CT scans decreased,
      mainly in the lower lung field. Passive smoking might have contributed to her
      airflow limitation.

PMID- 17228807
TI  - [Penicillamine-induced bronchiolitis obliterans diagnosed by transbronchial lung
      biopsy].
AB  - A 57-year-old woman had been treated with penicillamine (200 mg/day) for
      degenerative arthritis initially misdiagnosed as rheumatoid arthritis since 2003.
      She presented with dyspnea and was admitted to our hospital in 2004. Pulmonary
      function tests revealed mixed pattern of dysfunction with severe airway
      obstruction. Chest computed tomography showed mosaic ground-glass opacities.
      Bronchoalveolar lavage fluid (BALF) demonstrated increase in total cells and
      lymphocytes. Since specimens of transbronchial lung biopsy (TBLB) showed
      lymphocytic infiltration in membranous bronchiole and occlusion of the membranous
      bronchiole lumen, bronchiolitis obliterans was diagnosed by TBLB. After
      penicillamine, which had been administered for 7 months, was stopped, she was
      successfully treated with steroid and macrolides.

PMID- 17228808
TI  - [BALF lymphocyte CD 4/8 ratio in a case of sarcoidosis with radiological
      resolution].
AB  - A 60-year-old man was given a diagnosis of pulmonary and ocular sarcoidosis. His
      radiological abnormalities and visual disturbance resolved after two years. Ten
      years later, at age 70, squamous cell carcinoma was detected in the right lower
      lobe of the lung. Lymphocyte CD4/8 ratio in bronchoalveolar lavage fluid has
      remained at a high level for the previous 10 years and was 7.41 immediately
      before the operation. Chest CT and gallium scintigram could not detect
      abnormalities in mediastinal or hilar nodes. The tumor and right lower lobe were
      resected with hilar and mediastinal lymph nodes. Histological examination
      revealed that there were numerous epithelioid cell granulomas in mediastinal and
      hilar lymph nodes. BALF analysis reflects residual granulomatous inflammation,
      even if the radiological findings do not show any abnormalities.

PMID- 17228810
TI  - [Two cases of meningeal carcinomatosis during gefitinib therapy for non-small
      cell lung cancer].
AB  - "Case 1" A 56-year-old woman who suffered from postoperative recurrent non-small
      cell lung cancer received gefitinib therapy. Approximately 7 months after the
      therapy was begun, although the intrathoracic disease responded to the treatment,
      she developed meningeal carcinomatosis and died of rapidly progressive central
      nervous system disease. "Case 2" A 46-year-old man with stage IV non-small cell
      lung cancer started gefitinib therapy after chemotherapy. The pulmonary lesions
      markedly improved responding to gefitinib therapy, however, approximately 6
      months after the therapy was begun, multiple brain metastasis and meningeal
      carcinomatosis were detected. Approximately 4 months after the diagnosis of
      meningeal carcinomatosis, he died of disease progression and disturbance of
      consciousness. It has been reported that the central nervous system is a frequent
      metastatic site of non-small cell lung cancer in patients treated with gefitinib.
      We report two cases of meningeal carcinomatosis that occurred during the period
      in which their intrathoracic disease was responding to gefitinib therapy. We
      should consider the possibility of metastatic central nervous system disease,
      even in patients in whom gefitinib therapy is apparently successful.

PMID- 17228809
TI  - [A case of squamous cell carcinoma of the lung with a high titer of proteinase 3
      antineutrophil cytoplasmic antibody].
AB  - A 57-year-old man who had a history of sinusitis was admitted to Ryugasaki
      Saiseikai hospital in April 2002 because of productive cough and bloody sputum.
      Chest radiographs and CT scans showed mediastinal lymphadenopathy and a solitary
      mass lesion with an irregular margin and cavity in the left lower lung field.
      Proteinase 3 antineutrophil cytoplasmic antibody (PR3 ANCA) was positive, and
      this is a sensitive and specific indicator of Wegener's granulomatosis. The
      pathological findings from transbronchial biopsy revealed squamous cell carcinoma
      of the lung, without the presence of vasculitis, accompanied by Wegener's
      granulomatosis. A partial response was finally obtained after three courses of
      paclitaxel and carboplatin. The serum level of PR3 ANCA decreased from 142 EU to
      16 EU. This case appears to have had parallel time courses of progression of
      squamous cell carcinoma of the lung and changes in serum PR3 ANCA level. This is
      of importance in considering the relationship of lung cancer and paraneoplastic
      vasculitis.

PMID- 17228812
TI  - ["Abnormal" cranial MRI findings observed in a 13-year-old girl with
      consciousness disturbances].

PMID- 17228813
TI  - [My history of study on child neurology].

PMID- 17228814
TI  - [Relationship between characteristic behaviors of children with AD/HD and
      mothers' parenting styles].
AB  - Previous studies have revealed that mothers of children with attention
      deficit/hyperactivity disorder (AD/HD) have an authoritarian parenting style.
      However, the psychological process of developing an authoritarian parenting style
      has yet to be clearly defined. To clarify this psychological process, the present
      study examined the hypothesis that the characteristic behaviors of children with
      AD/HD initially increase the mothers' parenting stress, which influences their
      parenting style. Thirty-six mothers of children with AD/HD (children's mean age:
      8.1 years) and the same number of controls (children's mean age: 8.4 years)
      participated in the present study. The mothers' parenting stress was assessed
      using the Japanese Parenting Stress Index. Parenting styles were assessed using
      the TK-style scale for evaluating the relationships between parents and children.
      The results indicated that the mothers of children with AD/HD had significantly
      higher scores than controls for all parenting stress items and negative parenting
      style variables (dissatisfaction, reproach, strictness, interference,
      inconsistency and disagreement of 10 attitudes). Stepwise multiple regression
      analysis revealed that the characteristic behaviors of children with AD/HD were
      associated with the degree of attachment in mothers, which was related to the
      strict and reproachful parenting style in the AD/HD group. These results suggest
      that mothers of children with AD/HD are likely to have a strict and reproachful
      parenting style as a result of a lack of attachment with the child.

PMID- 17228815
TI  - [A case of a child who developed Cushing reflex after a clinical diagnosis of
      brain death].
AB  - The author presents a case of brain death caused by salmonella encephalopathy in
      a 1-year-old girl. The patient suffered from fever, convulsive status, and coma.
      On the 5th day, her respiration was arrested. At that time, we confirmed the
      absence of brainstem reflexes. An electroencephalogram (EEG) showed a flat
      pattern. Only wave I was recordable in auditory brainstem responses (ABR). On the
      6th day, we obtained a flat EEG and a disappearance of all components of ABR. A
      simultaneous elevation of her heart rate and blood pressure was observed 14 to 18
      hours after the respiratory arrest. This phenomenon was equivalent to the Cushing
      reflex, which represents an autoregulation against increased intracranial
      pressure. Our case suggested that the activity of a part of the brainstem was
      preserved in spite of the absence of activities in EEG, ABR and brainstem
      reflexes at 14 hours after the onset of apnea.

PMID- 17228816
TI  - [Incidence of cerebral palsy in Himeji City in 1983-1997].
AB  - We retrospectively investigated the incidence, neuroimaging findings, and motor
      and intellectual disability of infants with cerebral palsy (CP) who were born
      between 1983 and 1997. The incidence of CP was found to have increased gradually
      and the major cause was periventricular leukomalacia. The prognosis of preterm
      infants was better than that of term infants. These findings suggest that the
      increase in the incidence of CP has been due mainly to changes in medical care
      for neonates.

PMID- 17228817
TI  - [Usefulness of L-arginine infusion for status epilepticus in mitochondrial
      myopathy, encephalopathy, lactic acidosis, and stroke-like episodes].
AB  - We encountered an 11-year-old girl with mitochondrial myopathy, encephalopathy,
      lactic acidosis, and stroke-like episodes (MELAS) who developed occipital lobe
      epilepsy at the age of 7 years and 4 months. Thereafter she had repeated status
      epilepticus associated with stroke-like episodes. Status epilepticus consisted of
      repetitive complex partial seizures with or without secondarily generalized tonic
      clonic seizures. The seizures did not respond to conventional anticonvulsive
      drugs, including diazepam, midazolam, phenytoin, lidocaine, chloral hydrate, and
      thiamylal sodium, and lasted for several hours (mean 9.5 hours). At the age of 11
      years, intravenous infusion of L-arginine (0.5 g/kg body weight) was first given
      five hours after the onset of status epilepticus. The seizures and
      electroencephalographic abnormalities improved dramatically. After the
      introduction of L-arginine, in addition to shortened duration of status
      epilepticus (mean 3 hours), clinical recovery from the status epilepticus was
      prompt, and the average hospitalization periods could be shortened. There were no
      obvious adverse effects, including vomiting, hypotension, and urticaria. Our
      experience suggests that early intravenous administration of L-arginine may be
      useful in the treatment of status epilepticus associated with stroke-like episode
      in patients with MELAS.

PMID- 17228818
TI  - [Valproate sodium and zonisamide associated interstitial pneumonitis in an
      infant].
AB  - A six month-old female infant developed dyspnea when she was treated with
      valproate sodium (VPA) and zonisamide (ZNS) for epileptic spasms. Two weeks after
      its onset, her dyspnea was exacerbated by respiratory syncytial virus (RSV)
      infection. We diagnosed interstitial pneumonitis (IP) based on her chest CT and
      high serum concentrations of KL-6 and surfactant protein D. Her dyspnea improved
      with the treatment which included steroids, neutrophil elastase inhibitor and
      discontinuation of VPA and ZNS. An allergic reaction probably explains the IP in
      our patient because steroids were effective. Her IP might have been exacerbated
      by several factors including the use of two anticonvulsants (VPA, ZNS), RSV
      infection, and physiological low serum IgA level of infants. Drug-induced
      interstitial lung disease should be remembered as a possible complication of
      anticonvulsant treatment, such as VPA and ZNS.

PMID- 17228819
TI  - [A case of cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL), diagnosed in the age of puberty].
AB  - We report a 13-year-old boy with cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL) at an early stage. He
      showed migraine, cognitive deficits, depressive episodes and areas of white
      matter hyperintensity on MRI. There were no first-degree relatives accompanied
      with similar symptoms. T2-and fluid-attenuated inversion recovery (FLAIR)-
      weighted brain MRI revealed areas of apparently symmetric high intensity in the
      deep white matter and periventicular caps. On ultrastructural studies of the
      biopsied skin, there were free granular osmiophilic materials (GOM) between
      vascular smooth muscle cells in the cutaneous vessels. But there were no
      excavations in the cell membranes that contained GOM. On immunostaining with
      Notch3 monoclonal antibodies, granular staining was not observed in vessels of
      the skin. No mutation was detected on DNA analysis of the Notch3 gene (exon 4 and
      part of exon 5) in peripheral leukocytes. Although the frequencies of migraine
      episodes and depressive episodes decreased with amitriptyline and ibuprofen, the
      cognitive deficits (delayed-recall impairment) and areas of white matter
      hyperintensity on MRI have been unchanged for the past four

PMID- 17228820
TI  - [Late infantile GM1 gangliosidosis with progressive dilatation of common bile
      duct and obstructive apnea--an autopsy case].
AB  - We report a 5-year-old autopsy case of late infantile type of GM1
      gangliosidosis,which developed rare respiratory and intestinal complications.
      Obstructive apnea by adenoidal hypertrophy was improved by adenoidectomy, but the
      right bronchus was compressed by hilar lymph node swellings. The lymph nodes
      could not be treated surgically because of her poor general condition. There was
      hyperplasia showing foamy histiocyte including mucopolysaccharide which
      demonstrated a vacuolar formation containing irregular arranged fibrillar
      material on electron microscopy. Cerebral atrophy progressed gradually, and
      epileptic apnea developed, which was intractable to all antiepileptic drugs
      administered. Glycolipid accumulation, showing membranous cytoplasmic body on
      electron microscopy, seemed to lead to neurodegeneration. Abdominal distension
      due to hepatosplenomegaly, common bile duct dilatation compressed by lymph node
      swelling of the caput pancreatis part, and enteroparalysis was uncontrolled.
      These findings suggest that severe glycolipid deposition in lymphoreticular
      organs can induce various complications in patients with late infantile type of
      GM1 gangliosidosis.

PMID- 17228821
TI  - [A case of Mobius syndrome presenting with symptoms of severe infantile form of
      congenital muscular disorder].
AB  - Mobius syndrome is a rare disorder characterized by congenital bilateral facial
      nerve palsy. Abducent palsy or other cranial nerve palsy, facial malformations,
      limb malformations, and skeletal malformations are common features associated
      with this syndrome. We report a 9-month-old infant in whom congenital muscular
      disorder was previously suspected because of facial muscle involvement (mask-like
      face), respiratory and swallowing disturbances, and hypotonia since birth. After
      an improvement in the respiratory infection, she showed slightly exaggerated deep
      tendon reflexes and an improvement in muscle tone. The occurrence of combined
      facial nerve palsy, glossopharyngeal nerve palsy, vagus nerve palsy, and
      hypoglossal nerve palsy strongly suggested that she had Mobius syndrome. Finally,
      the absence of the roots of bilateral facial nerves on an MRI confirmed that the
      disorder was Mobius syndrome. We propose that a thin slice MRI should be obtained
      to observe the cranial nerves around the brain stem if patients show symptoms of
      congenital myopathy or congenital myotonic dystrophy as well as facial nerve and
      other cranial nerve paralyses.

PMID- 17228822
TI  - [Dysgenesis of the carotid artery associated with congenital ipsilateral Horner
      syndrome].
AB  - We report a case with dysgenesis of the carotid artery associated with congenital
      Homer syndrome. A 6-year-old boy, who had undergone surgical repair for pulmonary
      atresia, ventricular septal defect, and patent ductus arteriosus at 20 months of
      age, presented with miosis of the left eye, and anhidrosis of the left face,
      neck, and shoulder girdle. Since the anhidrosis was obvious in early childhood,
      he was suspected as having congenital Horner syndrome. Cranial and cervical CT
      showed unpredicted abnormalities of the left carotid arteries, including the
      absence of an internal carotid artery (ICA), and hypoplasia of the common carotid
      and external carotid arteries. The anterior and middle cerebral arterial flow was
      supplied through the communicating arteries. Congenital agenesis of the ICA was
      highly suspected, because the left carotid canal could not be discerned at all.
      The concurrence of agenesis of ICA with ipsilateral Horner syndrome is accounted
      for by simultaneous organogenesis of the carotid artery and cervical sympathetic
      nerve, both of which are derived from neural crest cells. Developmental anomalies
      of the cervical neural crest, though rare, should be included in the differential
      diagnosis of congenital Homer syndrome.

PMID- 17228823
TI  - [Adaptation of English-written health-related quality of life measure for
      children].

PMID- 17228825
TI  - Failing trusts can be shut down.

PMID- 17228824
TI  - Dossier reveals true extent of management consultant spend.

PMID- 17228826
TI  - NHS Alliance. New agenda replaces targets.

PMID- 17228827
TI  - Reconfiguration. Where managers fear to tread, myths and legends may rush in.

PMID- 17228828
TI  - On demand management.

PMID- 17228829
TI  - Skilled analysts of little use to the NHS.

PMID- 17228830
TI  - Data briefing. What's driving the admissions rise.

PMID- 17228831
TI  - Maternity. Safe in their hands?

PMID- 17228832
TI  - Patient safety. On the danger list.

PMID- 17228833
TI  - Bullying. Killing them softly.

PMID- 17228834
TI  - [Selective elimination of meiosis-specific mRNA operates during the mitotic cell
      cycle].

PMID- 17228836
TI  - [CLE peptides regulate plant morphogenesis as intercellular signaling molecules].

PMID- 17228835
TI  - [Regeneration and plasticity of the injured central nervous system].

PMID- 17228837
TI  - [Functions of Smc5/6 complex revealed by ChIP-on-chip analysis].

PMID- 17228838
TI  - [Regulatory molecules for memory B cell response].

PMID- 17228839
TI  - [Structure and force-generation mechanism of dynein arms revealed by electron
      microscopy].

PMID- 17228841
TI  - [Protein secondary structure prediction].

PMID- 17228842
TI  - [Production of endoderm-derived visceral organ cells from ES cells].

PMID- 17228840
TI  - [Structure of a membrane protein in eicosanoid and glutathione metabolism by
      electron crystallography].

PMID- 17228843
TI  - [BugBuster purification kits].

PMID- 17228844
TI  - [B-PER bacterial protein extraction reagent].

PMID- 17228845
TI  - [CelLytic IB inclusion body solubilization reagent].

PMID- 17228846
TI  - [Heterozygosis H63D in patients with steatohepatitis and chronic hepatitis C].
AB  - OBJECTIVE: Classic hereditary hemochromatosis is an autosomal recessive iron
      overload disorder associated with mutation of the HFE gene. The homozygous
      genetic defect predisposes to a chain of events that may culminate in severe
      damage in multiple organs. Pathologic implications of heterozygous defect are
      still questionable; in fact since these individuals may have slight increases in
      intra-cellular iron, it has been questioned whether this would enhance damage
      from other diseases. We investigated whether steatohepatitis and chronic
      hepatitis C can be worsened by heterozygosis for C282Y and H63D. PATIENTS AND
      METHODS: We investigated 216 subjects with Steatohepatitis and/or chronic
      hepatitis C diagnosed by ultrasonography and liver biopsy with histological
      assessment compared with 110 healthy subjects. In all subjects we performed
      Saturated Transferrine, Plasma Ferritin and the research of HFE mutation by a
      Real Time Method. A statistical analysis was performed. RESULTS: A H63D mutation
      was present in 32/108 patients with Steatohepatitis, in 30/108 patients with
      chronic hepatitis C and in 22/110 healthy subjects. A C282Y mutation was present
      in 2/108 patients with chronic hepatitis C, in 4/108 with steatohepatitis and in
      2/108 healthy subjects. No significant difference was present about incidence of
      this mutation between pathological and healthy subjects. No significant
      differences have observed between pathological groups and normal group about the
      degree of histological damage. CONCLUSIONS: Our study revealed that
      steatohepatitis and chronic hepatitis C cannot be worsened by heterozygosis for
      C282Y and H63D.

PMID- 17228847
TI  - Osteoporosis prevention: a reasoned examination of food habits and physical
      activities in a schoolchildren population in central Italy.
AB  - OBJECTIVE: The dietary intake of calcium is fundamental for prevention of
      osteoporosis, especially in the first three decade of age to gain a valid peak
      bone mass; moreover physical activity is important for the same reason. The
      objective of our research is to examine the food habits and the way to practice
      sport in a homogenous population of schoolchildren. MATERIALS AND METHODS: Data
      were collected by an original questionnaire in 500 schoolchildren (238 males, 262
      females, 9-12 yrs) living in the centre of Italy. RESULTS: Data show that the
      calcium intake decreases while the age increases. According to the recommended
      daily calcium dose, the percentages of insufficient calcium intake were 21% in
      the 6 years old group, 35% in the 7 to 10 years old group and 52.5% in the 11 to
      14 years old group. Milk and dairy products cover 57% of the calcium needs (17%
      and 40% respectively), water covers 24% and the other foodstuffs 19%; moreover
      most children (43.5%) practice non competitive sports with a preference (58.3%)
      for no-weightbearing sports (mainly cycling) over weightbearing sports (mainly
      football). CONCLUSIONS. This survey suggests that a high percentage of young
      people do not take the recommended daily dose of calcium (especially interesting
      that becoming older with consequent lower parental control over the diet, the
      higher the incidence of poor calcium intake increases), then it would be
      recommendable to establish a national health program promoting appropriate
      physical exercise plus a correct calcium intake as early as the primary school.

PMID- 17228848
TI  - [Therapy optimization of heart failure through the evaluation of the plasma
      concentration variation of B-type natriuretic peptide].
AB  - AIM: Our research was based over the critical evaluation of the plasmatic
      concentration variation of B-type Natriuretic Peptide in emergency in patients
      with heart failure during therapy with diuretics, anti-aldosterone, ACE
      inhibitors, beta-blockers and nitroderivates. MATERIALS AND METHOD: We selected
      108 patients: 30 control subjects (average 58.40 +/- SD13.32 for 20 M, and 65 +/-
      SD 14.74 for 10 W), and 78 subjects (average 75.90 +/- SD 9.60 for 41 M, and
      77.89 +/- SD 8.62 for 37 W) arrived to the emergency and reception department for
      dyspnea and/or precordialgia and/or palpitations with heart failure diagnosis
      according to NYHA Classification. The variation of BNP concentration was
      evaluated in these subjects at the admission, after 1 week, and 1 month from the
      beginning of the therapy. RESULTS: Patients with heart failure had a BNP
      concentration high during all measurements. The values were high during
      admission, but after 1 week and after 1 month, they reduced reaching the balance.
      CONCLUSIONS: BNP evaluation is a good indicator for the diagnosis of heart
      failure and for improving the therapy. The main limit of BNP diagnostic role is
      the need of knowing in advance the specific values for each patient.

PMID- 17228849
TI  - [Role of green tea in oxidative stress prevention].
AB  - OBJECTIVE: Oxidative stress is a condition caused by an increase of Reactive
      Oxygen Species (ROS) or by a shortage of the mechanisms of cellular protection
      and antioxidant defence. ROS have a potential oxidative effect towards various
      cellular macromolecules: proteins, nucleic acids, proteoglycans, lipids, with
      consequent damages in several cellular districts and promotion of the ageing
      process of the organism. However, some substances are able to prevent and/or
      reduce the damages caused by ROS; therefore, they are defined antioxidant. The
      present research studied, in a group of subjects, the antioxidant effects of the
      green tea, that was administered with fruit and vegetables in a strictly
      controlled diet. MATERIALS AND METHODS: 50 subjects were selected and requested
      to daily consume 2-3 fruit portions (especially pineapple), 3-5 portions of
      vegetables (especially tomato) and 2-3 glasses of green tea for about 2 months to
      integrate the controlled basic diet. Some indicators of the oxidative stress were
      measured in the plasma before and after the integration period. RESULTS: The
      integration of a basic diet with supplements of fruit, vegetables and green tea
      turned out to be able in increasing both plasmatic total antioxidant capacity and
      endogenous antioxidant levels and to reduce the lipid peroxidation of the
      membranes, suggesting a reduction of the oxidative stress. CONCLUSIONS: These
      data suggest that an adequate supplement of antioxidants can prevent oxidative
      stress and correlated pathologies.

PMID- 17228850
TI  - Insulin glargine in patients with severe hepato-gastroenterology diseases and
      hyperglycemia receiving parenteral nutrition.
AB  - OBJECTIVE: The aim of this nonrandomized observational study is to verify and
      confirm whether it is possible to use insulin glargine (Lantus) subcutaneously in
      patients receiving parenteral nutrition (PN) and whether the analogue is capable
      of obtaining and maintaining good glycemic control without inducing hypoglycemia.
      MATERIALS AND METHODS: The sample is made up of 25 patients with severe hepato
      gastroenterology diseases receiving parenteral nutrition, diagnosed diabetics and
      non-diabetics, who had previously been prescribed traditional insulin therapy.
      All were to be given subcutaneous insulin glargine at a dosage equal to the
      average of insulin/day administered in the preceding days spent receiving PN.
      RESULTS: Twenty-five consecutive patients, not stratified in any way, were judged
      eligible in the last six months of 2004 and first eight months of 2005. Four out
      of these 25 cannot be evaluated, either because (2/4) they did not begin or
      complete the treatment with Lantus or because the proper number of glycemic tests
      were not done (2/4); 21/25 patients, 84% of the sample with a mean age of 65.9
      years (range 46-93 yr), finished the study and can be evaluated. The mean
      glycemic values after treatment with glargine were already better on the second
      day, and on the seventh day the difference was statistically significant. No
      hypoglycemias occurred which required medical intervention. CONCLUSIONS: This
      study confirms the possibility of using insulin glargine in patients receiving
      parenteral nutrition with hyperglycemia diagnosed diabetics or not diabetics.

PMID- 17228851
TI  - [Cat scratch pneumonia: a case report].
AB  - Pasteurella multocida infections can be caused by scratches or bites of many
      animals including pets. An unrecognized infection can lead to severe
      complications such as arthritis, osteomyelitis, respiratory infections and even
      meningitis or endocarditis. We present the case of a woman affected by soft
      tissue infection caused by Pasteurella multocida complicated by bacteremia and
      pneumonia.

PMID- 17228852
TI  - [Chronic exposure to styrene and psychiatric symptomatology: a case-control
      descriptive study].
AB  - BACKGROUND: Although the acute psychiatric consequences exerted by Styrene and
      other aromatic hydrocarbons are abundantly described, the effects produced by a
      low-dosages chronic exposure are not known, in spite of the wide employment in
      the field of industrial production. The aim of this study is to evaluate the
      psychiatric symptoms in a group of subjects exposed to styrene in comparison with
      a control group, not exposed to the substance. SUBJECTS AND METHODS: Twenty two
      qualified workers, divided into 11 subjects in charge of welding and resin
      tapping exposed to styrene, and 11 not exposed to neurotoxic substances, were
      evaluated through the Symptom Check List Revised (SCL-90-R), a scale for the
      global self-evaluation of psychiatric symptomatology. RESULTS: The statistical
      tests, herein utilized, showed a significant prevalence for the dimensions
      somatization and psychoticism in the exposed subjects to styrene as compared to
      the non-exposed subjects. CONCLUSIONS: The results of this study, although
      limited by the paucity of the sample, emphasize the importance of an early
      diagnosis and evaluation of the clinical predictors in subjects exposed to
      styrene. The relatively low concentration levels of styrene in the working area
      of the subjects exposed underlines the opportunity to arrange preventive
      evaluation strategies for a prompt intervention in those cases with a clear
      syndromic presentation.

PMID- 17228853
TI  - [Airborne contact dermatitis].
AB  - A comprehensive bibliographical retrieval of case reports on "airborne contact
      dermatitis" (ACD) was performed. The present review deals with the first cases
      published in 1986, 1991, 2001 by Huygens as well as by Dooms-Goossens, and
      continues with the other pertaining clinical presentations until to day. Solid
      particles, rather than gases or droplets, are the most frequently reported causes
      of ACD.

PMID- 17228854
TI  - [Periodontitis and systemic diseases].
AB  - Periodontitis is a condition of suffering of gingival and periodontal tissues. To
      the light of the available knowledges till now on the pathogenetic mechanisms of
      such affection is possible to affirm that the different risk factors can
      influence onset of it, evolution and therapeutic possibility. In the examination
      of the risk factors in the development of the periodontal pathology the effects
      of the systemic conditions on the health of the oral cavity has been considered,
      as well as the influence of the periodontal pathology on the onset and on the
      evolution of several systemic pathologies and related to some physiological
      conditions (e.g. the pregnancy).

PMID- 17228855
TI  - [Metabolomics and medical practice].
AB  - High resolution NMR spectroscopy, currently known as "metabolomics", is a
      technology enabling the rapid, noninvasive and low cost determination of low
      molecular weigh metabolites (e.g. aminoacids) in biological fluids such as
      plasma, urine, saliva, cerebrospinal fluid and others. According to Nicholson
      "Metabolomics is the quantitative measurement of the dynamic multiparametric
      metabolic response of living systems to pathophysiological stimuli or genetic
      modification". Over the past 10 years this technology made it possible to
      discover of a number of lesser-known organ-specific metabolites that has been
      demonstrated to be reliable indicators of both organ function and viability.
      Consequently metabolomics has been used, with interesting results, for the
      functional evaluation of many organs (kidney, liver, heart), drug toxicity and
      post-transplant monitoring. The international literature demonstrates a growing
      interest for this technology and its capabilities.

PMID- 17228856
TI  - [Merkel cell carcinoma].
AB  - Merkel cell carcinoma is a rare form of skin cancer of likely neuroendocrine
      origin wich affects mainly white population in sun-exposed areas. It is an
      aggressive tumor and survival is dependent on stage at the time of diagnosis. The
      staging evaluation include CT imaging and recently PET scan. Surgical excision
      with or without lymph node dissection, followed by postoperative radiotherapy in
      stage II disease, is the standard treatment of non metastatic disease. The role
      of adjuvant chemotherapy is still controversial. In patients with metastatic
      disease, chemotherapy regimens active in small cell lung cancer are generally
      used. The combination of cyclophosphamide, doxorubicin and vincristine (CAV) has
      an overall response rate of 75%, whereas the response rate of etoposide in
      combination with cisplatin or carboplatin is 60%. Experience with other
      therapeutic agents, such as tumor necrosis factor, interferon and octreotide is
      scanty. Recently, encouraging preliminary results with targeted agents have been
      reported. Our experience in 14 patients, four of whom treated with chemotherapy
      for advanced disease, is in agreement with literature

PMID- 17228857
TI  - Receptor-mediated delivery of antigens to dendritic cells: anticancer
      applications.
AB  - Recently, there has been a surge of interest in the use of ex vivo antigen-pulsed
      dendritic cells (DCs) in the immunotherapy for cancer. DCs are powerful adjuvants
      with the ability to prime naive CD4+ and CD8+ T cells. As antigen sources,
      various preparations, including peptides, proteins, crude tumor lysates, and DCs
      transfected or transformed with various viruses, have been used. These procedures
      that involve the isolation of patient DCs and reintroduction after in vitro
      manipulation are time-consuming and expensive. The DC populations used frequently
      in ex vivo clinical studies are IL-4 and GM-CSF cultured DCs that may not
      represent the in vivo DC populations. An attractive method of targeting in vivo
      DCs is to utilize various ligands or antibodies that bind discrete populations of
      DCs. These cell surface receptors will direct the antigen to different antigen
      processing pathways depending on the targeted receptor to induce cytotoxic T cell
      or T helper responses. This review will discuss the various approaches and
      receptors that have been used for antigen targeting that may eventually be
      translated to alternative DC-based immunotherapies.

PMID- 17228858
TI  - Advances in development of dopaminergic aporphinoids.

PMID- 17228859
TI  - Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors.
AB  - A papaverine based pharmacophore model for PDE10A inhibition was generated via
      SBDD and used to design a library of 4-amino-6,7-dimethoxyquinazolines. From this
      library emerged an aryl ether pyrrolidyl 6,7-dimethoxyquinazoline series that
      became the focal point for additional modeling, X-ray, and synthetic efforts
      toward increasing PDE10A inhibitory potency and selectivity versus PDE3A/B. These
      efforts culminated in the discovery of 29, a potent and selective brain
      penetrable inhibitor of PDE10A.

PMID- 17228860
TI  - Design and synthesis of potent inhibitors of the malaria parasite dihydroorotate
      dehydrogenase.
AB  - Pyrimidine biosynthesis presents an attractive drug target in malaria parasites
      due to the absence of a pyrimidine salvage pathway. A set of compounds designed
      to inhibit the Plasmodium falciparum pyrimidine biosynthetic enzyme
      dihydroorotate dehydrogenase (PfDHODH) was synthesized. PfDHODH-specific
      inhibitors with low nanomolar binding affinities were identified that bind in the
      N-terminal hydrophobic channel of dihydroorotate dehydrogenase, the presumed site
      of ubiquinone binding during oxidation of dihydroorotate to orotate. These
      compounds also prevented growth of cultured parasites at low micromolar
      concentrations. Models that suggest the mode of inhibitor binding is based on
      shape complementarity, matching hydrophobic regions of inhibitor and enzyme, and
      interaction of inhibitors with amino acid residues F188, H185, and R265 are
      supported by mutagenesis data. These results further highlight PfDHODH as a
      promising new target for chemotherapeutic intervention in prevention of malaria
      and provide better understanding of the factors that determine specificity over
      human dihydroorotate dehydrogenase.

PMID- 17228861
TI  - Structure-activity relationships of cyclic peptide-based chemokine receptor CXCR4
      antagonists: disclosing the importance of side-chain and backbone
      functionalities.
AB  - Previously, we have identified a highly potent CXCR4 antagonist 2 [cyclo(-D-Tyr1
      Arg2-Arg3-Nal4-Gly5-)] and its Arg2 epimer 3 [cyclo(-D-Tyr1-D-Arg2-Arg3-Nal4-Gly5
      )] by the screening of cyclic pentapeptide libraries that were designed based on
      the structure-activity relationship studies on 14-residue peptidic CXCR4
      antagonist 1. In the present study, a new series of analogues of 2 and 3 were
      synthesized to evaluate the influences of peptide side-chain and backbone
      modification on bioactivities. Based on the Ala-scanning study, in which each
      residue in 2 and 3 was replaced with Ala having the identical chirality,
      substitution of Arg3 and Nal4 [Nal = L-3-(2-naphthyl)alanine] with Ala (compounds
      6, 7, 10, 11) led to significant loss of the potency, indicating these amino
      acids are more important contributors to the bioactivity. For the cyclic peptide
      backbone, several modifications including d/l-Ala or cyclic amino acids
      substitution at the Gly5 position and sequential N-methylation on amide nitrogens
      were conducted. Among the analogues, compounds 13 [cyclo(-D-Tyr1-Arg2-Arg3-Nal4-D
      Ala5-)] and 32 [cyclo(-D-Tyr1-D-MeArg2-Arg3-Nal4-Gly5-)] were close in potency to
      the most potent lead 2. NMR and conformational analysis indicated that both of
      these analogues favor the same backbone conformation as 2, whereas similar
      analysis of less potent analogues indicates that an altered backbone conformation
      is favored. The conformational analysis showed that steric repulsion by a 1,3
      allylic strain-like effect across the planar peptide bond might contribute to the
      conformational preferences of cyclic pentapeptides.

PMID- 17228862
TI  - Isothiazoloquinolones with enhanced antistaphylococcal activities against
      multidrug-resistant strains: effects of structural modifications at the 6-, 7-,
      and 8-positions.
AB  - We describe the biological evaluation of isothiazoloquinolones (ITQs) having
      structural modifications at the 6-, 7-, and 8-positions. Addition of a methoxy
      substituent to C-8 effected an increase in antibacterial activity against
      methicillin-resistant Staphylococcus aureus (MRSA) and a decrease in cytotoxic
      activity against Hep2 cells. Removal of fluorine from C-6 or replacement of the C
      8 carbon with a nitrogen compromised anti-MRSA activity. When the groups attached
      at C-7 were compared, the anti-MRSA activity decreased in the order 6
      isoquinolinyl > 4-pyridinyl > 5-dihydroisoindolyl > 6-tetrahydroisoquinolinyl.
      The compound with the most desirable in vitro biological profile was 9
      cyclopropyl-6-fluoro-8-methoxy-7-(2-methylpyridin-4-yl)-9H-isothiazolo[5,4
      b]quinoline-3,4-dione (7g). This ITQ demonstrated (i) strong in vitro anti-MRSA
      activity (MIC90 = 0.5 microg/mL), (ii) strong inhibitory activities against S.
      aureus DNA gyrase and topoisomerase IV, with weak activity against human
      topoisomerase II, (iii) weak cytotoxic activities against three cell lines, and
      (iv) efficacy in an in vivo murine thigh model of infection employing MRSA.

PMID- 17228863
TI  - Stereoselectivity by enantiomeric inhibitors of matrix metalloproteinase-8: new
      insights from molecular dynamics simulations.
AB  - Molecular Dynamics simulations in aqueous solution were performed for the matrix
      metalloproteinase-8 (MMP-8) free catalytic domain and for its complexes with the
      (R)- and (S)-[1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl] phosphonate.
      The 144-155 loop of the enzyme undergoes a drastic decrease of mobility once
      complexed with both enantiomers. The two enantiomers induce a different decrease
      of conformational entropy upon complexation. The higher affinity of the R
      enantiomer can be related to the lower loss of conformational entropy
      accompanying its binding. The differences in the dynamical behavior of the
      protein induced by the two enantiomers are discussed at molecular level and the
      mode of binding of the simulated complexes is compared with that previously
      determined by X-ray crystallography.

PMID- 17228864
TI  - Slow-onset, long-duration, alkyl analogues of methylphenidate with enhanced
      selectivity for the dopamine transporter.
AB  - Methylphenidate analogues, in which the carbomethoxy has been replaced by an
      alkyl group and with different phenyl substituents, have been synthesized and
      tested in monoamine transporter assays. As predicted from a pharmacophore model,
      most of the RR/SS diastereomers showed high potency as dopamine reuptake
      inhibitors. Analogues with a 4-chlorophenyl group and an unbranched initial alkyl
      atom had consistently enhanced selectivity for the dopamine transporter. The most
      potent compounds were those with a three- or four-carbon chain. The "inactive"
      RS/SR diastereomers showed substantial activity when the phenyl substituent was
      3,4-dichloro. On a locomotor assay, one compound was found to have a slow onset
      and a long duration of action. The activity of these compounds provides
      additional evidence for a conformational/superposition model of methylphenidate
      with cocaine-like structures. A ketone analogue, obtained by hydrogenating a
      previously described vinylogous amide, had activity similar to that of
      methylphenidate.

PMID- 17228865
TI  - Synthesis and metabotropic glutamate receptor activity of S-oxidized variants of
      (-)-4-amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate: identification of
      potent, selective, and orally bioavailable agonists for mGlu2/3 receptors.
AB  - (-)-4-Amino-2-thiabicyclo-[3.1.0]hexane-4,6-dicarboxylate (LY389795, (-)-3) is a
      highly potent and selective agonist of metabotropic glutamate receptors 2 (mGlu2)
      and 3 (mGlu3). As part of our ongoing research program, we have prepared S
      oxidized variants of (-)-3, compounds (-)-10, (+)-11 (LY404040), and (-)-12
      (LY404039). Each of these chiral heterobicyclic amino acids displaced specific
      binding of the mGlu2/3 receptor antagonist 3H-2S-2-amino-2-(1S,2S-2
      carboxycycloprop-1-yl)-3-(xanth-9-yl)propanoic acid (3H-LY341495) from membranes
      expressing recombinant human mGlu2 or mGlu3 and acted as potent agonists in cells
      expressing these receptor subtypes. Docking of the most potent of these
      derivatives, (+)-11, to mGlu2 revealed the possibility of an additional H-bond
      interaction between the sulfoxide oxygen of (+)-11 with tyrosine residue Y236.
      Pharmacokinetic analysis of mGlu active enantiomers (+)-11 and (-)-12 in rats
      showed each to be well absorbed following oral administration. Consistent with
      their mGlu2/3 agonist potency and pharmacokinetic properties, both (+)-11 and (-)
      12 blocked phencyclidine-evoked ambulations in a dose-dependent manner,
      indicating their potential as nonclassical antipsychotic agents.

PMID- 17228866
TI  - Ester-based precursors to increase the bioavailability of quercetin.
AB  - Plant polyphenols exhibit a variety of potentially useful biochemical properties
      in vitro, but their evaluation and clinical exploitation in vivo is hampered by
      their limited bioavailability. Precursors exhibiting resistance to phase II
      metabolism during absorption are therefore desirable. We report here the
      synthesis as well as stability and solubility studies of several ester
      derivatives of quercetin (3,3',4',5,7-pentahydroxy flavone), most of which
      comprise an aminoacyl group. To model transepithelial absorption, we tested
      transport across supported tight monolayers of MDCK-1, MDCK-2, and Caco-2 cells.
      Quercetin itself was extensively conjugated by all three types of cells. A few of
      our precursors did not cross the monolayers, but others did, undergoing partial
      deacylation. No phase II conjugation was observed during transport of these
      compounds across MDCK or some Caco-2 clones. With other Caco-2 lines complete
      deacylation occurred, followed by metabolism of quercetin. Since elimination of
      residual acyl groups is expected to take place in vivo, ester derivatives of
      polyphenols may constitute a useful method to increase systemic aglycone
      concentrations.

PMID- 17228867
TI  - Optimization of monocarboxylate transporter 1 blockers through analysis and
      modulation of atropisomer interconversion properties.
AB  - We have previously described a novel series of potent blockers of the
      monocarboxylate transporter, MCT1, which show potent immunomodulatory activity in
      an assay measuring inhibition of PMA/ionomycin-induced human PBMC proliferation.
      However, the preferred compounds had the undesirable property of existing as a
      mixture of slowly interconverting rotational isomers. Here we show that variable
      temperature NMR is an effective method of monitoring how alteration to the nature
      of the amide substituent can modulate the rate of isomer exchange. This led to
      the design of compounds with increased rates of rotamer interconversion.
      Moreover, some of these compounds also showed improved potency and provided a
      route to further optimization.

PMID- 17228868
TI  - Green tea catechins inhibit bacterial DNA gyrase by interaction with its ATP
      binding site.
AB  - Catechins are the main ingredients of green tea extracts and have been shown to
      possess versatile biological activities, including antimicrobial. We determined
      that the catechins inhibit bacterial DNA gyrase by binding to the ATP binding
      site of the gyrase B subunit. In the group of four tested catechins,
      epigallocatechin gallate (EGCG) had the highest activity, followed by epicatechin
      gallate (ECG) and epigallocatechin (EGC). Specific binding to the N-terminal 24
      kDa fragment of gyrase B was determined by fluorescence spectroscopy and
      confirmed using heteronuclear two-dimensional NMR spectroscopy of the EGCG-15N
      labeled gyrase B fragment complex. Protein residues affected by binding to EGCG
      were identified through chemical shift perturbation. Molecular docking
      calculations suggest that the benzopyran ring of EGCG penetrates deeply into the
      active site while the galloyl moiety anchors it to the cleft through interactions
      with its hydroxyl groups, which explains the higher activity of EGCG and ECG.

PMID- 17228869
TI  - Development of orally bioavailable and CNS penetrant biphenylaminocyclopropane
      carboxamide bradykinin B1 receptor antagonists.
AB  - A series of biphenylaminocyclopropane carboxamide based bradykinin B1 receptor
      antagonists has been developed that possesses good pharmacokinetic properties and
      is CNS penetrant. Discovery that the replacement of the trifluoropropionamide in
      the lead structure with polyhaloacetamides, particularly a trifluoroacetamide,
      significantly reduced P-glycoprotein mediated efflux for the series proved
      essential. One of these novel bradykinin B1 antagonists (13b) also exhibited
      suitable pharmacokinetic properties and efficient ex vivo receptor occupancy for
      further development as a novel approach for the treatment of pain and
      inflammation.

PMID- 17228870
TI  - Dissection of the recognition properties of p38 MAP kinase. Determination of the
      binding mode of a new pyridinyl-heterocycle inhibitor family.
AB  - The main recognition characteristics of the ATP binding site of p38 mitogen
      activated protein kinase alpha (p38alpha MAPK) have been explored by a
      combination of modeling and bioinformatics techniques, making special emphasis in
      the characteristics of the site that justifies binding specificity with respect
      to other MAP kinases. Particularly, we have analyzed the binding mode of a new
      family of p38 MAPK inhibitors based on the pyridinyl-heterocycle core. This
      family of compounds has a marked pseudosymmetry and can exist in different
      tautomeric forms, which makes the determination of the binding mode especially
      challenging. A combination of homology modeling, quantum mechanics, classical
      docking, and molecular dynamics calculations allowed us to determine the main
      characteristics defining the binding mode of this new scaffold in the ATP binding
      site of p38alpha. A set of free energy calculations allowed us to verify the
      binding mode proposed, giving an overall excellent agreement with the
      experimental values. Finally, the binding mode of this new family of compounds
      was compared to that of other members of the pyridinyl and pyrimidinyl
      heterocycle class.

PMID- 17228871
TI  - Synthesis and structure-activity relationships of new benzodioxinic lactones as
      potential anticancer drugs.
AB  - A set of disubstituted tetracyclic lactones has been synthesized and tested for
      potential antitumor activity. Several of them possess a noticeable cytotoxicity
      against L1210 and HT-29 colon cells in vitro. Relationships between chain nature
      and biological properties were sought. Lactones with a pentyl or hexyl
      substituent at C-11 are the most active ones. The introduction of a functional
      group at the side chain of C-11 modified the potency; carboxylic acid and primary
      amine decreased the cytotoxicity, whereas a cyano group increased the activity.
      An extensive structure-activity relationship study of these derivatives,
      including carbon homologues and bioisosteres has been performed. The synthesis
      and cytotoxicity of these compounds are discussed. Two lactones are recognized as
      potential lead compounds.

PMID- 17228872
TI  - Synthesis and transfection efficiencies of new lipophilic polyamines.
AB  - A homologous series of lipophilic polyamines was synthesized and evaluated for
      DNA delivery and transfection efficiency. The series contained 1,4-butanediamine,
      1,8-octanediamine, 2-[2-(2-amino-ethoxy)-ethoxy]-ethylamine, homospermidine, and
      homospermine covalently attached via their N1 terminus to a 3,4-bis(oleyloxy)
      benzyl motif. In addition, homospermidine and homospermine were also attached via
      amide linkers. The homospermidine derivatives (i.e., benzyl tether 25 and
      benzamide tether 27) showed a 3-fold and 4-fold respective enhancement in
      delivery of AlexaFluor-488-labeled DNA over the butanediamine analogue 22.
      Homospermine derivative 26 was shown to inhibit 14C-spermine uptake (IC50
      approximately 10 microM), which implied that 26 is able to compete effectively
      for polyamine recognition sites on the cell surface. This study demonstrated that
      the number and position of the positive charges along the polyamine scaffold
      plays a key role in DNA delivery and in determining the transfection efficiency.

PMID- 17228873
TI  - Synthesis and SAR of [1,2,4]triazolo[1,5-a]pyrimidines, a class of anticancer
      agents with a unique mechanism of tubulin inhibition.
AB  - The synthesis and SAR of a series of triazolopyrimidines as anticancer agents are
      described. Treatment of 5-chloro-6-(trifluorophenyl)-N-fluoroalkyl
      [1,2,4]triazolo[1,5-a]pyrimidin-7-amine with an alcohol, a thiol, or an
      alkylamine provided the corresponding final compounds. A clear SAR requirement
      has been established for optimal activity. A (1S)-2,2,2-trifluoro-1
      methylethylamino group or an achiral 2,2,2-trifluoroethylamino group is required
      at the 5-position to achieve high potency. On the phenyl ring, both fluoro atoms,
      at the positions ortho to the triazolopyrimidine core, are needed for optimal
      activity. At the position para to the triazolopyrimidine core, on the phenyl
      ring, the best activity is achieved with an oxygen linkage followed by a three
      methylene unit, and an alkylamino or a hydroxy group. The mechanism of action for
      this series of triazolopyrimidines was shown to be unique in that they promoted
      tubulin polymerization in vitro, but did not bind competitively with paclitaxel.1
      Instead, they inhibit the binding of vincas to tubulin. Selected compounds were
      studied further, and it was shown that these compounds were able to overcome
      resistance attributed to several multidrug resistance transporter proteins. Lead
      compounds were shown to inhibit tumor growth in several nude mouse xenograft
      models, with high potency and efficacy, when dosed either orally or
      intravenously.

PMID- 17228874
TI  - Beta-methyl substitution of cyclohexylalanine in Dmt-Tic-Cha-Phe peptides results
      in highly potent delta opioid antagonists.
AB  - The opioid peptide TIPP (H-Tyr-Tic-Phe-Phe-OH, Tic:1,2,3,4-tetrahydroisoquinoline
      3-carboxylic acid) was substituted with Dmt (2',6'-dimethyltyrosine) and a new
      unnatural amino acid, beta-MeCha (beta-methyl-cyclohexylalanine). This double
      substitution led to a new series of opioid peptides displaying subnanomolar delta
      antagonist activity and mu agonist or antagonist properties depending on the
      configuration of the beta-MeCha residue. The most promising analog, H-Dmt-Tic
      (2S,3S)-beta-MeCha-Phe-OH was a very selective delta antagonist both in the mouse
      vas deferens (MVD) assay (Ke = 0.241 +/- 0.05 nM) and in radioligand binding
      assay (K i delta = 0.48 +/- 0.05 nM, K i mu/K i delta = 2800). The epimeric
      peptide H-Dmt-Tic-(2S,3R)-beta-MeCha-Phe-OH and the corresponding peptide amide
      turned out to be mixed partial mu agonist/delta antagonists in the guinea pig
      ileum and MVD assays. Our results constitute further examples of the influence of
      Dmt and beta-methyl substitution as well as C-terminal amidation on the potency,
      selectivity, and signal transduction properties of TIPP related peptides. Some of
      these compounds represent valuable pharmacological tools for opioid research.

PMID- 17228875
TI  - Novel quinolizidinyl derivatives as antiarrhythmic agents.
AB  - Eighteen analogues of lidocaine, mexiletine, and procainamide were synthesized,
      replacing their aminoalkyl chains with the rigid and cumbersome quinolizidine
      nucleus. The target compounds were tested for antiarrhythmic, inotropic, and
      chronotropic effects on isolated guinea pig (gp) heart tissues and to assess
      calcium antagonist activity. Most compounds exhibited from moderate to high
      antiarrhythmic activity, and compounds 7, 9, and 19 were more active and potent
      than quinidine and lidocaine, while producing only modest inotropic,
      chronotropic, and vasorelaxant effects. These compounds were studied on
      spontaneously beating Langendorff-perfused gp heart. While quinidine and
      amiodarone produced a dose-dependent prolongation of all the ECG intervals,
      compounds 7, 9, and 19, even at concentrations 10-20 times higher than EC50 for
      the antiarrhythmic activity, only moderately prolonged the PR and QT intervals,
      leaving unchanged the QRS complex. Ether 7 deserves further investigations due to
      its interesting cardiovascular profile.

PMID- 17228876
TI  - SAR of a series of 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3
      alpha]pyridines as potent inhibitors of human eosinophil phosphodiesterase.
AB  - The potency and physical properties of a previously reported 7-oxo-4,5,6,7
      tetrahydro-1H-pyrazolo[3,4-c]pyridine series of human eosinophil
      phosphodiesterase inhibitors were improved by tying the lactam moiety into a
      triazolo ring. The resulting 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3
      alpha]pyridine series provided nonionizable analogs with melting point properties
      suitable for micronization. Substitution at the 3-position of the 5,6-dihydro
      (9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridine tricycle led to a 2
      thienyl analog, 19 (tofimilast), a potent PDE4 inhibitor with low oral
      bioavailability and no emesis-associated behaviors in ferrets at plasma
      concentrations up to 152 ng/mL.

PMID- 17228877
TI  - Synthesis and cancer chemopreventive activity of zapotin, a natural product from
      Casimiroa edulis.
AB  - An efficient method has been developed to synthesize zapotin (5,6,2',6'
      tetramethoxyflavone), a component of the edible fruit Casimiroa edulis, on a
      multigram scale. The synthesis utilizes a regioselective C-acylation of a
      dilithium dianion derived from a substituted o-hydroxyactophenone to afford a
      beta-diketone intermediate that can be cyclized to zapotin in good overall yield,
      thus avoiding the inefficient Baker-Venkataraman rearrangement pathway. Zapotin
      was found to induce both cell differentiation and apoptosis with cultured human
      promyelocytic leukemia cells (HL-60 cells). In addition, the compound inhibits 12
      O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC)
      activity with human bladder carcinoma cells (T24 cells), and TPA-induced nuclear
      factor-kappa B (NF-kappaB) activity with human hepatocellular liver carcinoma
      cells (HepG2 cells). These data suggest that zapotin merits further investigation
      as a potential cancer chemopreventive agent.

PMID- 17228878
TI  - Effects of azaspiracid-1, a potent cytotoxic agent, on primary neuronal cultures.
      A structure-activity relationship study.
AB  - Azaspiracids (AZAs) are marine phycotoxins with an unknown mechanism of action,
      implicated in human intoxications. We investigated the effect of azaspiracid-1
      (AZA-1) on the cytosolic calcium concentration ([Ca2+]c), intracellular pH (pHi),
      and neuron viability in neuronal cultures. AZA-1 increased [Ca2+]c and decreased
      neuronal viability. The effects of several fragments of the AZA-1 molecule (13
      different chemical structures) were examined. The ent-ABCD-azaspiracid-1 (2)
      showed similar potency to AZA-1 (1) in increasing [Ca2+]c but higher cytotoxity
      than AZA-1. The chemical structures containing only the ABCD or the ABCDE ring
      domains (3-8) caused a [Ca2+]c increase but did not alter cell viability. The
      compounds containing only the FGHI ring domain of AZA-1 (9-14) did not modify the
      [Ca2+]c or the cell viability. Therefore, the effect of AZA-1 on [Ca2+]c depends
      on the presence of the ABCD or the ABCDE-ring structure, but the complete
      chemical structure is needed to produce neurotoxic effects.

PMID- 17228879
TI  - Design and synthesis of glycoside inhibitors of glioma and melanoma growth.
AB  - An N-acetylglucosaminide derivative with a pentaerythritol substituent at
      position C-6 was previously synthesized and shown to inhibit neural tumor growth.
      Now, we report the preparation of a series of new synthetic compounds introducing
      systematic changes in the nature, polarity, and size of the sugar substituents.
      The antimitotic activity of the new compounds was tested on cultured rat (C6) and
      human (U-373) glioma lines and on a human melanoma line (A-375). The antimitotic
      and antitumoral activity of the new compounds on glioma cell lines increased up
      to 2 orders of magnitude with respect to the parent compound or was abolished,
      permitting a detailed structure-function analysis of the new antitumorals. One of
      the glycosides inhibited melanoma division with an ID50 below the micromolar
      range.

PMID- 17228880
TI  - Synthesis and biological evaluation of novel 1-deoxy-1-[6
      [((hetero)arylcarbonyl)hydrazino]- 9H-purin-9-yl]-N-ethyl-beta-D
      ribofuranuronamide derivatives as useful templates for the development of A2B
      adenosine receptor agonists.
AB  - The lack of molecules endowed with selective and potent agonistic activity toward
      the hA2B adenosine receptors has limited the studies on this pharmacological
      target and consequently the evaluation of its therapeutic potential. We report
      the design and the synthesis of the first potent (EC50 in the nanomolar range)
      and selective hA2B adenosine receptor agonists consisting of 1-deoxy-1-[6
      [((hetero)arylcarbonyl)hydrazino]-9H-purin-9-yl]-N-ethyl-beta-D
      ribofuranuronamide derivatives. The concurrent effect of 6-substitution of the
      purine nucleus with a ((hetero)arylcarbonyl)hydrazino function and a 2-chloro
      substitution has been investigated in such NECA derivatives.

PMID- 17228881
TI  - Carbonic anhydrase inhibitors. DNA cloning, characterization, and inhibition
      studies of the human secretory isoform VI, a new target for sulfonamide and
      sulfamate inhibitors.
AB  - The secretory isozyme of human carbonic anhydrase (hCA, EC 4.2.1.1), hCA VI, has
      been cloned, expressed, and purified in a bacterial expression system. The
      kinetic parameters for the CO2 hydration reaction proved hCA VI to possess a kcat
      of 3.4 x 10(5) s-1 and kcat/KM of 4.9 x 10(7) M-1 s-1 (at pH 7.5 and 20 degrees
      C). hCA VI has a significant catalytic activity for the physiological reaction on
      the same order of magnitude as the ubiquitous isoform CA I or the transmembrane,
      tumor-associated isozyme CA IX. A series of sulfonamides and one sulfamate have
      been tested for their interaction with this isozyme. Simple benzenesulfonamides
      were rather ineffective hCA VI inhibitors, with inhibition constants in the range
      of 1090-6680 nM. Better inhibitors were detected among such derivatives bearing 2
      or 4-amino-, 4-aminomethyl-, or 4-hydroxymethyl moieties or among halogenated
      sulfanilamides (KI values of 608-955 nM). Some clinically used compounds, such as
      acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide,
      brinzolamide, topiramate, sulpiride, and indisulam, or the orphan drug
      benzolamide, showed effective hCA VI inhibitory activity, with inhibition
      constants of 0.8-79 nM. The best inhibitors were brinzolamide and sulpiride (KI
      values of 0.8-0.9 nM), the latter compound being also a CA VI-selective
      inhibitor. The metallic taste reported as a side effect after the treatment with
      systemic sulfonamides may be due to the inhibition of the salivary CA VI. Some of
      the compounds investigated in this study might be used as additives in
      toothpastes for reducing the acidification produced by the relevant CO2 hydrase
      activity of enamel CA VI, which leads to the formation of protons and bicarbonate
      and may have a role in cariogenesis.

PMID- 17228882
TI  - Novel sulfamide analogs of oleoylethanolamide showing in vivo satiety inducing
      actions and PPARalpha activation.
AB  - Long chain saturated and unsaturated alkyl sulfamide and propyl sulfamide
      derivatives, analogs of oleoylethanolamide, have been synthesized and evaluated
      in vivo and in vitro as peroxisome proliferator activated receptor alpha
      (PPARalpha) activators. Additionally, the anorexic effects of the new compounds
      have been studied in vivo in food-deprived rats. Among the active compounds N
      octadecyl-N'-propylsulfamide (7) has been identified as a potent hypolipidemic
      compound, a potent feeding suppressant, and a concentration-dependent activator
      of PPARalpha.

PMID- 17228883
TI  - Synthesis and antimalarial activity of side chain modified 4-aminoquinoline
      derivatives.
AB  - A new series of side-chain modified 4-aminoquinolines have been synthesized and
      found active against P. falciparum in vitro and P. yoelli in vivo. Compounds 6,
      11, 12, and 19 exhibited superior in vitro activity compared to chloroquine.
      Selected compounds 6, 12, and 19 exhibited significant suppression in the in vivo
      assay. These analogs form a complex with hematin and inhibit the beta-hematin
      formation, suggesting that this class of compounds act on a heme polymerization
      target.

PMID- 17228887
TI  - Dual relationship between large gold clusters (antifullerenes) and carbon
      fullerenes: a new lowest-energy cage structure for Au50.
AB  - Recent theoretical prediction and experimental confirmation of cage
      configurations for Au clusters have stimulated considerable interest in finding
      novel gold clusters exhibiting high stability. We use a dual relationship between
      gold antifullerene cages with all triangular faces and carbon fullerenes with all
      degree 3 vertices to construct a large number of Au50 antifullerene cages by
      omnicapping and dualization procedures. Among these cages we find a new D6d cage
      as the lowest-energy configuration of Au50. The unusual stability of this new
      Au50 cage is associated with spherical aromaticity and sp-d hybridization.

PMID- 17228885
TI  - New fluorescent 2-phenylindolglyoxylamide derivatives as probes targeting the
      peripheral-type benzodiazepine receptor: design, synthesis, and biological
      evaluation.
AB  - Fluorescent ligands for the peripheral-type benzodiazepine receptor (PBR)
      featuring the 7-nitrobenz-2-oxa-1,3-diazol-4-yl moiety were synthesized, based on
      N,N-dialkyl-2-phenylindol-3-ylglyoxylamides, a potent, selective class of PBR
      ligands previously described by us. All the new ligands are moderately to highly
      potent at the PBR, with a complete selectivity over the central benzodiazepine
      receptor. Results from fluorescence microscopy showed that these probes
      specifically labeled the PBR at the mitochondrial level in C6 glioma cells.

PMID- 17228884
TI  - Structure-guided optimization of estrogen receptor binding affinity and
      antagonist potency of pyrazolopyrimidines with basic side chains.
AB  - 2,3-Diarylpyrazolo[1,5-a]pyrimidines are estrogen receptor (ER) antagonists of
      modest potency that we have described previously. Guided by the crystal structure
      of an ER-ligand complex that we have obtained with one of these compounds, we
      prepared analogs that contain a basic side chain at the 2- or 3-aryl group and
      quickly found one that, according to the structure-based prediction, shows an
      increase in binding affinity and antagonist potency and a loss of residual
      agonist activity.

PMID- 17228888
TI  - Driving Energies of Hydrogen Scrambling Motions in CH5+.
AB  - A comprehensive quantum chemistry study with natural bond orbital analysis is
      performed to reveal the intrinsic properties of the floppy potential energy
      surface of the smallest methonium ion CH5+. In contrast to the low-energy
      barriers of Cs(I)-->Cs(II)-->Cs(I) and Cs(I)-->C2v-->Cs(I) that correspond to the
      H2 rotation and H-flip motions, the remarkably larger intramolecular interaction
      energies are the driving power to mimic the hydrogen scrambling in CH5+. As for
      the H2 rotation and H-flip motions, the hyperconjugative and electrostatic
      interactions compete strongly. They together with other interactions compensate
      for each other and lead to the floppy potential energy surface.

PMID- 17228889
TI  - Attacking boron nucleophiles: NMR properties of five-membered diazaborole rings.
AB  - This paper reports computed NMR spectral data for the diazaborole anion (C2H4B1N2
      ) and the corresponding neutral five-membered rings with B-H (C2H5B1N2,
      diazaborole) and B-Li (C2H4B1Li1N2, Li-diazaborole) bonds, which are the central
      moieties of newly synthesized nucleophilic organoboryl five-membered rings,
      recently reported by Segawa et al. (Science 2006, 314, 113). Both spin-spin
      coupling constants and chemical shifts were obtained using high-level ab initio
      calculations. These data are a necessary complement to the very scarce
      experimental information available.

PMID- 17228890
TI  - Reactions of nitrogen monoxide on cobalt cluster ions: reaction enhancement by
      introduction of hydrogen.
AB  - Absolute cross sections for NO chemisorption, NO decomposition, and cluster
      dissociation in the collision of a nitrogen monoxide molecule, NO, with cluster
      ions Con+ and ConH+ (n=2-5) were measured as a function of the cluster size, n,
      in a beam-gas geometry in a tandem mass spectrometer. Size dependency of the
      cross sections and the change of the cross sections by introduction of H to Con+
      (effect of H-introduction) are explained by a statistical model based on the RRK
      theory, with the aid of the energetics obtained by a DFT calculation. It was
      found that the reactions are governed by the energetics rather than dynamics. For
      instance, Co3+ does not react appreciably with NO because the reactions are
      endothermic, while Co3H+ does because the reaction becomes exothermic by the H
      introduction.

PMID- 17228891
TI  - Strategies to improve photostabilities in ultrasensitive fluorescence
      spectroscopy.
AB  - Given the particular importance of dye photostability for single-molecule and
      fluorescence fluctuation spectroscopy investigations, refined strategies were
      explored for how to chemically retard dye photobleaching. These strategies will
      be useful for fluorescence correlation spectroscopy (FCS), fluorescence-based
      confocal single-molecule detection (SMD) and related techniques. In particular,
      the effects on the addition of two main categories of antifading compounds,
      antioxidants (n-propyl gallate, nPG, ascorbic acid, AA) and triplet state
      quenchers (mercaptoethylamine, MEA, cyclo-octatetraene, COT), were investigated,
      and the relevant rate parameters involved were determined for the dye Rhodamine
      6G. Addition of each of the compound categories resulted in significant
      improvements in the fluorescence brightness of the monitored fluorescent
      molecules in FCS measurements. For antioxidants, we identify the balance between
      reduction of photoionized fluorophores on the one hand and that of intact
      fluorophores on the other as an important guideline for what concentrations to be
      added for optimal fluorescence generation in FCS and SMD experiments. For nPG/AA,
      this optimal concentration was found to be in the lower micromolar range, which
      is considerably less than what has previously been suggested. Also, for MEA,
      which is a compound known as a triplet state quencher, it is eventually its
      antioxidative properties and the balance between reduction of fluorophore cation
      radicals and that of intact fluorophores that defines the optimal added
      concentration. Interestingly, in this optimal concentration range the triplet
      state quenching is still far from sufficient to fully minimize the triplet
      populations. We identify photoionization as the main mechanism of photobleaching
      within typical transit times of fluorescent molecules through the detection
      volume in a confocal FCS or SMD instrument (<1-20 ms), and demonstrate its
      generation via both one- and multistep excitation processes. Apart from
      reflecting a major pathway for photobleaching, our results also suggest the
      exploitation of the photoinduced ionization and the subsequent reduction by
      antioxidants for biomolecular monitoring purposes and as a possible switching
      mechanism with applications in high-resolution microscopy.

PMID- 17228892
TI  - Ab initio molecular dynamics study of methanol adsorption on copper clusters.
AB  - The preferential structures of small copper clusters Cun (n=2-9) and the
      adsorption of methanol molecules on these clusters are examined with first
      principles, molecular dynamics simulations. The results show that the copper
      clusters undergo systematic changes in bond length and bond order associated with
      altering their preferential structures from one-dimensional structures, to two
      dimensional and three-dimensional structures. The results also indicate that low
      coordination number sites on the copper clusters are both the most favorable for
      methanol adsorption and have the greatest localization of electronic charge. The
      simulations predict that charge transfer between the neutral copper clusters and
      the incident methanol molecules is a key process by which adsorption is
      stabilized. Importantly, the changes in the dimensionality of the copper clusters
      do not significantly influence methanol adsorption.

PMID- 17228893
TI  - Conformers and photochemistry of propyl nitrites: a matrix isolation study.
AB  - The infrared spectra of both constitutional isomers (n and i) of propyl nitrite
      have been recorded in an Ar matrix. Conformational analysis and assignments of
      the vibrational transitions have been carried out on the basis of quantum
      chemical calculations. Assignment of spectral lines to different conformers was
      also aided experimentally, by utilizing the different rate of photodecomposition
      of the conformers, as well as by employing conformational cooling using a
      supersonic jet as the inlet source for matrix deposition. The rate of
      photodecomposition is primarily determined by the steric alignment of the nitrite
      group, whereas jet cooling affects mainly the conformation of the alkyl tail. On
      the basis of these experimental observations and computational predictions two to
      three conformers of isopropyl nitrite and eight conformers of n-propyl nitrite
      were identified. After broadband ultraviolet-visible (UV-vis) photolysis of
      isopropyl nitrite in the matrix, HNO, acetone, HNO.acetone complex, acetaldehyde,
      and nitrosomethane were identified as the main products. Furthermore, in a small
      amount, NO and possibly the isopropoxy radical were also present in the matrix.
      Photolysis of n-propyl nitrite yielded HNO, propanal, and their 1:1 complex as
      the main products together with a small amount of NO and cis-1-nitrosopropanol.

PMID- 17228894
TI  - Vibrational energy relaxation rates of H2 and D2 in liquid argon via the
      linearized semiclassical method.
AB  - The vibrational energy relaxation (VER) rates for H2 and D2 in liquid argon
      (T=152 K, rho=1.45x1022 cm-3) are calculated using the linearized semiclassical
      (LSC) method (J. Phys. Chem. 2003, 107, 9059, 9070). The calculation is based on
      Fermi's golden rule. The VER rate constant is expressed in terms of the quantum
      mechanical force-force correlation function, which is then estimated using the
      LSC method. A local harmonic approximation (LHA) is employed in order to compute
      the multidimensional Wigner integrals underlying the LSC approximation. The H2-Ar
      and D2-Ar interactions are described by the three-body potential of Bissonette et
      al. (J. Phys. Chem. A 1996, 105, 2639). The LHA-LSC-based VER rate constants for
      both D2 and H2 are found to be about 2-3 orders of magnitude slower than those
      obtained experimentally. However, their ratio agrees quantitatively with the
      corresponding experimental result. In contrast, the classical VER rate constants
      are found to be 8-9 orders of magnitude slower than those obtained
      experimentally, and their ratio is found to be qualitatively different from the
      corresponding experimental result.

PMID- 17228895
TI  - Thermal lensing in a supercritical water medium.
AB  - A pulsed, two-beam, thermal lensing experiment was performed to determine the
      concentration of aqueous solutes above the critical point of water. Despite a
      very significant mirage effect due to thermal gradients in the cell and
      absorption by water itself, the thermal lensing signal strength for aqueous
      benzoic acid in supercritical water was found to be linear with concentration in
      the sub-millimolar range. Although thermal lensing experiments in aqueous media
      are notoriously insensitive, the sharp density gradient near the critical point
      considerably improves the signal intensity. In this study a short-pulse pump 266
      nm YAG laser and continuous low-power probe Ar ion beam were both focused into a
      supercritical water cell, giving a lensing signal whose strength could be
      maximized by changing the overlap of the two beams.

PMID- 17228896
TI  - Two-photon absorption properties of iron(II) and ruthenium(II) trischelate
      complexes of 2,2':4,4' ':4',4' ''-quaterpyridinium ligands.
AB  - A series of RuII or FeII trischelate complex salts containing N-methyl/aryl
      2,2':4,4' ':4',4' ''-quaterpyridinium ligands that has previously been subjected
      to quadratic nonlinear optical studies (Coe, B. J. et al. J. Am. Chem. Soc. 2005,
      127, 13399) has now been investigated for two-photon absorbing behavior. Z-scan
      measurements using a 750 nm laser afford reasonably large two-photon absorption
      (2PA) cross-sections sigma2 of ca. 62-180 GM for the RuII complexes, but only
      very weak 2PA is observed for the FeII compounds. The excited-state and 2PA
      properties of the representative chromophore [RuII(Me2Qpy2+)3]8+ (Me2Qpy2+=N'
      ',N' ''-dimethyl-2,2':4,4' ':4',4' ''-quaterpyridinium) have also been
      investigated by using semiempirical intermediate neglect of differential
      overlap/multireference-determinant single and double configuration interaction
      computations with the optimized geometry obtained via density functional theory.
      The calculated sigma2 value of ca. 624 GM at 1.70 eV for this metal-to-ligand
      charge-transfer chromophore is about 10 times larger than that obtained from the
      Z-scan studies.

PMID- 17228897
TI  - Experimental determination of the H2SO4/(NH4)2SO4/H2O phase diagram.
AB  - We have experimentally investigated the water and sulfuric acid-rich regions of
      the H2SO4/(NH4)2SO4/H2O ternary liquid/solid phase diagram using differential
      scanning calorimetry (DSC) and infrared spectroscopy of thin films. We present
      the liquid/solid ternary phase diagram for temperatures below 373 K and H2SO4
      concentrations below 60 wt %. We have determined two ternary eutectics and two
      tributary reaction points for this system in the regions studied. It is also seen
      that sulfuric acid tetrahydrate (SAT) forms as a metastable solid over a large
      concentration range. Two true binary systems have been identified: ice/letovicite
      and SAT/ammonium bisulfate. Finally, we have compared our results to the
      predictions of the aerosol inorganics model and have found significant
      differences both in the final melting points and in the location of some of the
      phase boundaries including a significant discrepancy in the invariant points
      predicted versus those observed.

PMID- 17228898
TI  - Measurements of the 12C/13C kinetic isotope effects in the gas-phase reactions of
      light alkanes with chlorine atoms.
AB  - The carbon kinetic isotope effects (KIEs) of the reactions of several light non
      methane hydrocarbons (NMHC) with Cl atoms were determined at room temperature and
      ambient pressure. All measured KIEs, defined as the ratio of the Cl reaction rate
      constants of the light isotopologue over that of the heavy isotopologue
      (Clk12/Clk13) are greater than unity or normal KIEs. For simplicity, measured
      KIEs are reported in per mil according to Clepsilon=(Clk12/Clk13 -1)x1000 per
      thousand unless noted otherwise. The following average KIEs were obtained (all in
      per thousand): 10.73+/-0.20 (ethane), 6.44+/-0.14 (propane), 6.18+/-0.18
      (methylpropane), 3.94+/-0.01 (n-butane), 1.79+/-0.42 (methylbutane), 3.22+/-0.17
      (n-pentane), 2.02+/-0.40 (n-hexane), 2.06+/-0.19 (n-heptane), 1.54+/-0.15 (n
      octane), 3.04+/-0.09 (cyclopentane), 2.30+/-0.09 (cyclohexane), and 2.56+/-0.25
      (methylcyclopentane). Measurements of the 12C/13C KIEs for the Cl atom reactions
      of the C2-C8 n-alkanes were also made at 348 K, and no significant temperature
      dependence was observed. To our knowledge, these 12C/13C KIE measurements for
      alkanes+Cl reactions are the first of their kind. Simultaneous to the KIE
      measurement, the rate constant for the reaction of each alkane with Cl atoms was
      measured using a relative rate method. Our measurements agree with published
      values within+/-20%. The measured rate constant for methylcyclopentane, for which
      no literature value is available, is (2.83+/-0.11)x10-10 cm3 molecule-1 s-1,
      1sigma standard error. The Clepsilon values presented here for the C2-C8 alkanes
      are an order of magnitude smaller than reported methane Clepsilon values
      (Geophys. Res. Lett., 2000, 27, 1715), in contrast to reported OHepsilon values
      for methane (J. Geophys. Res. (Atmos.), 2001, 106, 23, 127) and C2-C8 alkanes (J.
      Phys. Chem. A, 2004, 108, 11537), which are all smaller than 10 per thousand.
      This has important implications for atmospheric modeling of saturated NMHC stable
      carbon isotope ratios. 13C-structure reactivity relationship values (13C-SRR) for
      alkane-Cl reactions have been determined and are similar to previously reported
      values for alkane-OH reactions.

PMID- 17228899
TI  - Water-induced reconstruction that affects mobile ions on the surface of calcite.
AB  - Time-sequenced contact-force micrographs show that the (104) calcite cleavage
      surface reconstructs in humid air through pit formation and film growth. After 8
      h at 80% relative humidity (RH), 50% to 80% of the surface is covered by islands
      that are flat-topped and 1-nm high. The lateral growth rates of individual
      islands are 4.2+/-0.4 nm min-1 in the 41 direction and 1.8+/-0.4 nm min-1 in the
      48 direction, resulting in islands having distinct major and minor axes. On some
      samples, a contiguous, 1.5-nm-high film rapidly grows between the islands and the
      pits. The areal expansion rate of the film is 500 times faster than that of the
      islands. Gaps between the contiguous film and the islands expand and contract,
      which suggests that mass is exchanged between them and that both are loosely
      bound. Complementing the topographic images, polarization heights are
      simultaneously measured by polarization-force microscopy. The polarization
      heights of the islands and the contiguous film are -6 to -10 nm and -4 to -5 nm,
      respectively, compared to their respective topographic heights of +1.0 and +1.5
      nm. Under our experimental conditions, the polarization heights are a surrogate
      for the local dielectric constant of the sample epsilon and arise from a
      convolution of the mobility and the density of surface ions. The polarization
      heights imply that epsilonsubstrate>epsilonfilm>epsilonisland. Changes in
      topographic and polarization heights at 20% and 50% RH suggest that the
      structures of the islands are in dynamic equilibrium with the adsorbed water. Our
      evidence suggests that the islands contain loosely bound water and may therefore
      be a hydrated calcium carbonate phase stabilized by the calcite surface.

PMID- 17228900
TI  - QTAIM charge-charge flux-dipole flux models for the infrared fundamental
      intensities of difluoro- and dichloroethylenes.
AB  - A quantum theory of atoms in molecules (QTAIM) charge-charge flux-dipole flux
      (CCFDF) decomposition of the MP2/6-311++G(3d,3p) level molecular dipole moment
      derivatives is reported for the cis-, trans-, and 1,1-difluoroethylenes and the
      cis- and trans-dichloroethylenes. Although the dipole moment derivatives and
      infrared fundamental intensities calculated at the MP2 level are overestimated
      for high-intensity bands corresponding to CF and CC stretching vibrations, the
      overall agreement is good with a root-mean-square (rms) error of 19.6 km mol-1
      for intensities ranging from 0 to 217.7 km mol-1. The intensities calculated from
      the QTAIM/CCFDF model parameters are in excellent agreement with those calculated
      directly by the MP2/6-311++G(3d,3p) approach with only a 1.8 km mol-1 rms error.
      A high negative correlation (r=-0.91) is found between the charge flux and dipole
      flux contributions to the dipole moment derivatives. Characteristic values of
      charge, charge flux, and dipole flux contributions are found for CF, CCl, and CH
      stretching derivatives. The CH stretching derivatives provide especially
      interesting results with very high charge flux and dipole flux contributions with
      opposite signs. The charge, charge flux, and dipole flux contributions are found
      to be transferable from the cis to the trans isomers providing accurate
      predictions of the theoretical trans intensities with rms errors of 8.6 km mol-1
      for trans-difluoroethylene and 5.9 km mol-1 for trans-dichloroethylene.

PMID- 17228901
TI  - Predicting new molecular species of potential interest to atmospheric chemistry:
      the isomers HSBr and HBrS.
AB  - Coupled cluster singles and doubles with perturbative contributions of connected
      triples CCSD(T) theory with a series of correlation consistent basis sets was
      used to predict the existence and characterize for the first time the structures,
      harmonic frequencies, and energetic quantities of the isomeric species HSBr and
      HBrS, as well as the transition state connecting them. These calculations
      consider extrapolation to the complete basis set (CBS) limit, corrections for
      scalar relativistic effects using the second-order Douglas-Kroll-Hess
      Hamiltonian, and also correlation of the bromine d electrons in addition to the
      14 valence electrons. The species HSBr was found to be more stable than HBrS by
      50.93 kcal/mol, with a high barrier height of 60.00 kcal/mol for the
      interconversion into HBrS. The smaller barrier of 7.90 kcal/mol (ZPE included)
      for the reverse process, however, should favor a rapid interconversion of HBrS
      into HSBr if HBrS can also be initially present in a potential synthetic route.
      If trapped in a matrix, their harmonic frequencies will allow for an unambiguous
      distinction between the two species. Scalar relativistic corrections and
      correlation of 24 electrons, although minor for the present purpose of a first
      time, but accurate, characterization of these species, are needed if chemical
      accuracy is also pursued. A test of the DFT/B3LYP approach in describing this
      type of system resulted in good energetic quantities, but geometric parameters
      and frequencies still lack spectroscopic accuracy. Whether HSBr can act as a
      temporary bromine reservoir and/or a source of reactive bromine and HS radicals
      requires further studies that are underway in our group.

PMID- 17228902
TI  - Computational study of the reactions of SiH3X (X=H, Cl, Br, I) with HCN.
AB  - Ab initio calculations were carried out for the reactions of silane and
      halosilanes (SiH3X, X=H, Cl, Br, I) with HCN. Geometries of the reactants,
      transition states, intermediates and products were optimized at HF, MP2, and
      B3LYP levels of theory using the 6-31G(d) and 6-31G(d,p) basis sets. Energies
      were also obtained using G3MP2 and G3B3 levels of theory. Intrinsic reaction
      coordinate (IRC) calculations were performed to characterize the transition
      states on the potential energy surface. It was found that HCN can react with
      silane and halosilanes via three different mechanisms. One involves HX
      elimination by a one-step pathway producing SiH3CN. The second mechanism consists
      of H2 elimination, producing SiH2XCN via a one-step pathway or three multiple
      step pathways. The third mechanism involves dissociation of SiH3X to various
      products, which can then react with HCN. Activation energies, enthalpies, and
      free energies of activation along with the thermodynamic properties (DeltaE,
      DeltaH, and DeltaG) of each reaction pathway were calculated. The reaction of
      SiH3X with HCN produce different products depending on substituent X. We have
      found that the standard 6-31G(d) bromine basis set gave results which were in
      better agreement with the G3MP2 results than for the Binning-Curtiss basis set.
      Computed heats of formation (DeltaHf) for SiH3CN, SiH3NC, SiH2ClCN, SiH2BrCN,
      SiH2ICN, SiHCl, SiHBr, and SiHI were found to be 133.5, 150.8, -34.4, 23.6,
      102.4, 48.7, 127.1, and 179.8 kJ mol-1, respectively. From enthalpies calculated
      at G3MP2, we predict that the DeltaHf for SiH2 to be 262.8 kJ mol-1 compared to
      the experimental value of 273.8+/-4.2 kJ mol-1.

PMID- 17228903
TI  - (39)K NMR of solid potassium salts at 21 T: effect of quadrupolar and chemical
      shift tensors.
AB  - 39K Solid State NMR spectra (static and magic angle spinning (MAS)) on a set of
      potassium salts measured at 21.14 T show that the chemical shift range for K(+)
      ions in diamagnetic salts is well in excess of 100 ppm contrary to previous
      assumptions that it was quite small. Inequivalent potassium sites in crystals can
      be resolved through differences in chemical shifts, with chemically similar sites
      showing differences of over 10 ppm. The quadrupolar coupling constants obtained
      from MAS and solid echo experiments on powders cover the range from zero for
      potassium in cubic environments in halides to over 3 MHz for the highly
      asymmetric sites in K2CO3. Although the quadrupolar effects generally dominate
      the 39K spectra, in several instances, we have observed subtle but significant
      contributions of chemical shift anisotropy with values up to 45 ppm, a first such
      observation. Careful analysis of static and MAS spectra allows the observation of
      the various chemical shift and quadrupole coupling tensor components as well as
      their relative orientations, thereby demonstrating that high-field 39K NMR
      spectroscopy in the solid state has a substantial sensitivity to the local
      environment with parameters that will be of considerable value in materials
      characterization and electronic structure studies.

PMID- 17228904
TI  - Kinetics and thermodynamics of sucrose hydrolysis from real-time enthalpy and
      heat capacity measurements.
AB  - We report a real time study of the enthalpy release and heat capacity during the
      course of HCl-catalyzed hydrolysis of sucrose to fructose and glucose.
      Measurements were performed during both isothermal conditions and during slow
      heating and then cooling at a controlled rate. The reaction rate constant of the
      first-order kinetics follows an Arrhenius relation with activation energy of
      109.2 kJ/mol of sucrose. On hydrolysis, the enthalpy decreases by 14.4 kJ/mol of
      sucrose at 310 K, and the heat capacity, Cp, increases by 61 J mol-1 K-1 of
      sucrose in the solution. The enthalpy of hydrolysis decreases with increase in
      the temperature and DeltaCp on hydrolysis increases. The effects are attributed
      to change in the configurational and vibrational partition functions as one
      covalent bond in sucrose breaks to form two molecules, which then individually
      form additional hydrogen bonds and alter the water's structure in the solution.
      Cp of the solution increases with temperature less rapidly before sucrose
      hydrolysis than after it. This may reflect an increase in the configurational
      contribution to Cp as the hydrogen bond population changes.

PMID- 17228905
TI  - Fluorescent probes alter miscibility phase boundaries in ternary vesicles.
AB  - We use 2H NMR to study the effects of probes on the miscibility transition in
      multilamellar vesicles of di(18:1) phosphatidylcholine (PC; DOPC), chain
      perdeuterated di(16:0)PC (DPPCd62), and cholesterol both with and without 0.5 mol
      % of the fluorescent probes DiIC12 and DiOC18. Both probes raise the miscibility
      transition temperature in dispersions of 1:1 DOPC/DPPCd62 + 30% cholesterol but
      to differing extents. In membranes containing the popular probe DiIC12, the
      fraction of DPPCd62 lipids in the liquid disordered phase is increased, and the
      ordering of that phase is reduced even at low temperatures. All findings are
      consistent with a probe-induced expansion of the entire miscibility phase
      boundary. We examine membranes with smaller DiIC12 fractions and find a
      significant increase in transition temperature for samples with 0.05 mol %
      DiIC12, demonstrating that trace components can dramatically alter membrane phase
      behavior.

PMID- 17228906
TI  - Origin of the anomalous two-photon absorption in fluorescent protein DsRed.
AB  - The red fluorescent protein DsRed displays a two-photon excitation band around
      760 nm which is not accompanied by any feature in the corresponding one-photon
      spectral region (380 nm). By means of time-dependent density functional theory,
      we are able to explain such an effect, as arising from an electronic excitation
      of the DsRed chromophore with ability to couple with a charge-transfer state,
      through an effective two-photon absorption channel.

PMID- 17228907
TI  - From controllable attached isolation moieties to possibly highly efficient
      nonlinear optical main-chain polyurethanes containing indole-based chromophores.
AB  - For the first time, the indole-based NLO chromophores were embedded into the
      polymer main chain, and different isolation groups were attached to their donor
      side with the efforts of adjusting the NLO properties of the resultant main-chain
      polyurethanes, according to the site isolation principle. Thanks to the main
      chain structure and the advantages of the indole-based chromophores, all the
      polymers show excellent transparency, good processability, thermal stability, and
      relatively good NLO effects. The tested NLO properties of the polymers
      demonstrate that there is a suitable isolation group present for the sulfonyl
      based chromophore to boost its microscopic beta value to a possibly higher
      macroscopic NLO property efficiently.

PMID- 17228908
TI  - Microstructure of beta-lactoglobulin/pectin coacervates studied by small-angle
      neutron scattering.
AB  - Small-angle neutron scattering (SANS) has been used to investigate the
      microstructure of beta-lactoglobulin/pectin coacervates prepared by different
      initial protein/polysaccharide weight ratio (r), sodium chloride concentration
      (C(NaCl)), and pectin charge density. The higher r and higher pectin charge
      density lead to higher scattering intensity at small q range (0.007 Angstrom(-1)
      < q < 0.02 Angstrom(-1)), suggesting that the charges of pectin chains are
      screened significantly by the binding of oppositely charged protein molecules,
      leading to a tighter aggregation of pectin chains. On the other hand, the
      appearance of a shoulder peak at intermediate q range (0.04 Angstrom(-1) < q <
      0.2 Angstrom(-1)) is used to interpret the formation of protein domains in beta
      lactoglobulin/pectin coacervates. At C(NaCl) = 0.1 M, the coacervate of beta
      lactoglobulin and pectin A does not show a shoulder peak at intermediate q range
      at r = 10:1, suggesting that protein molecules are separately bound on pectin
      chains. However, a shoulder peak appears at intermediate q range at r = 20:1 and
      30:1, and the average protein domain size estimated from the shoulder peak
      position is 7.2 and 8.5 nm, respectively, for these two coacervates. When C(NaCl)
      increases from 0.05 to 0.2 M, the shoulder peak shifts toward smaller q and
      becomes broader, indicating that the addition of a higher amount of salt leads to
      a more heterogeneous coacervate structure. Pectin B with a lower linear charge
      density favors the formation of larger protein domains. The formation of protein
      domains in beta-lactoglobulin/pectin coacervates is partially ascribed to the
      self-aggregation of beta-lactoglobulin molecules. Two kinds of microstructures of
      beta-lactoglobulin/pectin coacervates with and without observable protein domains
      have been proposed.

PMID- 17228909
TI  - Linkage effects of chromium(III) acetylacetonato units on chiral induction of
      liquid crystal phases.
AB  - The linkage effects of polynuclear metal complexes on chiral induction have been
      studied by application of the chiral oligomers of acetylacetonato chromium(III)
      units as a dopant, inducing chiral nematic phases. The compounds were prepared by
      reacting [Cr(acac)(3)] (acac = acetylacetonato) and 1,1,2,2-tetraacetylethane
      (taetH(2)) in solid phase at 160 degrees C. Binuclear diastereomers were
      separated on a silica gel column, followed by chromatographic resolution on a
      chiral column packed with an ion-exchange adduct of Delta-[Ru(phen)(3)](2+) (phen
      = 1,10-phenanthroline) and synthetic hectorite. An enantiomeric pair (DeltaDelta-
      and LambdaLambda-[Cr(acac)(2)(taet)Cr-(acac)(2)]) and a meso species (DeltaLambda
      [Cr(acac)(2)(taet)Cr(acac)(2)]) were identified. The binuclear enantiomers were
      doped into a room-temperature nematic liquid crystal, N-methoxybenzylidene-4-n
      butylaniline. Helical twisting power (beta(M)) was found to be +97.9 and -88.9
      microm(-1) for LambdaLambda- and DeltaDelta-[Cr(acac)(2)(taet)Cr(acac)(2)],
      respectively. The values were compared with beta(M) for the monomeric enantiomers
      (+99.5 and -91.0 microm(-1) for Lambda- and Delta-[Cr(acac)(3)], respectively).
      The results are interpreted on the basis of the surface chirality model.
      DeltaDelta-[Cr(acac)(2)(taet)Cr(acac)(2)] was found to photoisomerize both in a
      hexane solution and in a liquid crystal phase of ZLI-1132. The quantum yield of
      photoisomerization in a liquid crystal phase was lowered to ca. 30% of that in a
      hexane solution.

PMID- 17228910
TI  - Novel porphyrin-incorporated hydrogels for photoactive intraocular lens
      biomaterials.
AB  - Novel surface-modified hydrogel materials have been prepared by binding charged
      porphyrins TMPyP (tetrakis(4-N-methylpyridyl)porphyrin) and TPPS (tetrakis(4
      sulfonatophenyl)porphyrin) to copolymers of HEMA (2-hydroxyethyl methacrylate)
      with either MAA (methacrylic acid) or DEAEMA (2-(diethylamino)ethyl
      methacrylate). The charged hydrogels display strong electrostatic interactions
      with the appropriate cationic or anionic porphyrins to give materials which are
      intended to be used to generate cytotoxic singlet oxygen (1O2) on photoexcitation
      and can therefore be used to reduce postoperative infection of the intraocular
      hydrogel-based replacement lenses that are used in cataract surgery. The UV/vis
      spectra of TMPyP in MAA:HEMA copolymers showed a small shift in the Soret band
      and a change from single exponential (161 micros) triplet decay lifetime in
      solution to a decay that could be fitted to a biexponential fit with two
      approximately equal components with tau = 350 and 1300 micros. O2 bubbling
      reduced the decay to a dominant (90%) component with a much reduced lifetime of 3
      micros and a minor, longer lived (20 micros) component. With D2O solvent the 1O2
      lifetime was measured by 1270 nm fluorescence as 35 micros in MAA:HEMA, compared
      to 67 mus in solution, although absorbance-matched samples showed similar yield
      of 1O2 in the polymers and in aqueous solution. In contrast to the minor
      perturbation in photophysical properties caused by binding TMPyP to MAA:HEMA,
      TPPS binding to DEAEMA:HEMA copolymers profoundly changed the 1O2 generating
      ability of the TPPS. In N2-bubbled samples, the polymer-bound TPPS behaved in a
      similar manner to TMPyP in its copolymer host; however, O2 bubbling had only a
      very small effect on the triplet lifetime and no 1O2 generation could be
      detected. The difference in behavior may be linked to differences in binding in
      the two systems. With TMPyP in MAA:HEMA, confocal fluorescence microscopy showed
      significant penetration of the porphyrin into the core of the polymer film
      samples (>150 microm). However, for TPPS in DEAEMA:HEMA copolymers, although the
      porphyrin bound much more readily to the polymer, it remained localized in the
      first 20 microm, even in heavily loaded samples. It is possible that the
      resulting high concentration of TPPS may have cross-linked the hydrogels to such
      an extent that it significantly reduced the solubility and/or diffusion rate of
      oxygen into the doped polymers. This effect is significant since it demonstrates
      that even simple electrostatic binding of charged porphyrins to hydrogels can
      have an unexpectedly large effect on the properties of the system as a whole. In
      this case it makes the apparently promising TPPS/DEAEMA:HEMA system a poor
      candidate for clinical application as a postoperative antibacterial treatment for
      intraocular lenses while the apparently equivalent cationic system TMPyP/MAA:HEMA
      displays all the required properties.

PMID- 17228911
TI  - Characteristics of wormlike pentaoxyethylene decyl ether C(10)E(5) micelles
      containing n-dodecanol.
AB  - The wormlike micelles formed with the surfactant pentaoxyethylene decyl ether
      C10E5 containing n-dodecanol were characterized by static (SLS) and dynamic light
      scattering (DLS) experiments. The SLS results have been analyzed with the aid of
      the light scattering theory for micelle solutions, thereby yielding the molar
      mass Mw(c) as a function of concentration c along with the cross-sectional
      diameter d of the micelle. The observed Kc/DeltaR0 as a function of c and the
      hydrodynamic radius RH as functions of Mw have been well described by the
      theories for the wormlike spherocylinder model. It has also been demonstrated
      that the apparent hydrodynamic radius RH,app(c) as a function of c is well
      described by a fuzzy cylinder theory which takes into account the hydrodynamic
      and direct collision interactions among micelles. Our previous results for the
      hexaoxyethylene dodecyl ether C12E6 micelles containing n-dodecanol were
      reanalyzed in the same scheme. It has been found that the micellar length
      increases with increasing concentration c or with raising temperature T
      irrespective of the composition of the C10E5 + n-dodecanol and C12E6 + n
      dodecanol systems. The length of the micelles at fixed c and T steeply increases
      with increasing weight fraction wd of n-dodecanol in both systems. The growth of
      the micelles accompanies the increase of the cross-sectional diameter d of the
      micelles and the results that the surfactant molecules are more densely assembled
      with increasing wd in order to keep n-dodecanol molecules inside the micelles.

PMID- 17228912
TI  - Characterization and catalytic functionalities of copper oxide catalysts
      supported on zirconia.
AB  - A series of zirconia supported copper oxide catalysts with varying copper
      loadings (1.2-19.1 wt %) were prepared by impregnation method. The catalysts were
      characterized by X-ray diffraction, UV-visible diffuse reflectance spectroscopy,
      X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction (TPR),
      and temperature-programmed desorption of CO2. Copper dispersion and metal area
      were determined by N2O decomposition method. X-ray diffraction patterns indicate
      the presence of crystalline CuO phase beyond 2.7 wt % of Cu on zirconia. UV
      visible diffuse reflectance spectra suggest the presence of two types of copper
      species on the ZrO2 support. XPS peaks intensity ratio of Cu 2p3/2 and Zr 3d5/2
      was compared with Cu dispersion calculated from N2O decomposition. TPR patterns
      reveal the presence of highly dispersed copper oxide at lower temperatures and
      bulk CuO at higher temperatures. The basicity of the catalysts was found to
      increase with Cu loading, and the activity of the catalysts was also found to
      increase with the increase in Cu loading up to 2.7 wt % Cu loading. The catalytic
      properties were evaluated for the dehydrogenation of cyclohexanol to
      cyclohexanone and were related to surface properties of the copper species
      supported on zirconia.

PMID- 17228914
TI  - Spontaneous formation of fractal structures on triglyceride surfaces with
      reference to their super water-repellent properties.
AB  - Alkylketene dimer (AKD), a kind of wax, has been known to form fractal surfaces
      spontaneously and show super water-repellency. Such formation of water-repellent
      and fractal surfaces was also found in this work for triglycerides. Since the
      crystal phase transitions of these waxes were well studied, we studied the
      formation of their fractal surfaces through contact angle measurements,
      differential scanning calorimetry (DSC), and X-ray diffraction (XRD). From time
      dependent contact angle measurements, it was found that the formation of super
      water-repellent surfaces with fractal structures occurred spontaneously also on
      the triglyceride surfaces at different temperatures. The freshly solidified
      triglyceride surfaces were almost transparent, and their initial contact angles
      of water were close to 110 degrees. The surfaces then became rough and clouded
      after being incubated for a certain time at a specified temperature. The super
      water-repellent surfaces were quite rough and showed fractal structures with the
      dimension of ca. 2.2 calculated from the scanning electron microscopic (SEM)
      images by the box-counting method. The phase transformation from a metastable
      state to a stable cystalline one after the solidification from the melt of
      triglycerides was clearly observed by DSC and XRD measurements. The fractal
      crystalline structures and the super water-repellency resulted from this phase
      transformation and the crystal growth. Ensuring the initial sample solidified
      into the metastable state and curing the surface at an appropriate temperature
      are key factors for the successful preparation of fractal triglyceride surfaces
      by the solidification method.

PMID- 17228913
TI  - Gram-negative outer and inner membrane models: insertion of cyclic cationic
      lipopeptides.
AB  - Most Gram-negative bacteria are susceptible to polymyxin B (PxB), and development
      of resistance to this cationic lipopeptide is very rare. PxB mechanism of action
      involves interaction with both the outer membrane (OM) and the inner membrane
      (IM) of bacteria. For the design of new antibiotics based on the structure of PxB
      and with improved therapeutic indexes, it is essential to establish the key
      features of PxB that are important for activity. We have used an approach based
      on mimicking the outer layers of the OM and the IM of Gram-negative bacteria
      using monolayers of lipopolysaccharide (LPS) or anionic 1-palmitoyl-2
      oleoylglycero-sn-3-phosphoglycerol (POPG), respectively, and using a combination
      of penetration assay, analysis of pressure/area curves, and Brewster angle
      microscopy to monitor surface morphology changes. Synthetic analogue sp-B
      maintains the basic structural characteristics of the natural compound and
      interacts with the OM and the IM in a similar way. Analogue sp-C, with a mutation
      of the sequence [d-Phe6-Leu7] into [d-Phe6-Dab7], shows that this hydrophobic
      domain is involved in LPS binding. The significant role of the positive charges
      is demonstrated with sp-Dap analogue, where l-alpha,gamma-diaminobutyric acid
      residues Dab1 and Dab8 are replaced by l-alpha,gamma-diaminopropionic acid (Dap),
      resulting in lower degrees of insertion in both LPS and PG monolayers. The
      importance of the N-terminal acyl chain is demonstrated with polymyxin B
      nonapeptide (PxB-np). PxB-np shows lower affinity for LPS compared to PxB, sp-B,
      or sp-C, but it does not insert into PG monolayers, although it binds
      superficially to the anionic film. Since PxB microbial killing appears to be
      mediated by osmotic instability due to OM-IM phospholipid exchange, the ability
      of the different peptides to induce membrane-membrane lipid exchange has been
      studied by use of phospholipid unilamellar vesicles. Results indicate that
      cationic amphipathicity determines peptide activity.

PMID- 17228915
TI  - Solvent release upon ion association from entropy data. II.
AB  - When a cation and an anion associate, the charge on the product is lower than
      that on the individual ions and solvent is released from their solvation shells
      to the bulk solvent. This release occurs when the associate is a solvent-shared
      or contact ion pair or an inner-type complex. The measurable molar entropy change
      involved is considered to be made up of four contributions: translational,
      rotational, electrostatic, and desolvation entropies. The former three can be
      calculated from the properties of the ions and solvents involved; hence, the
      fourth is obtained by difference. The release of solvent molecules from the
      crystalline frozen solvent to the liquid on melting is analogous to the solvent
      release from translational immobilization in the solvation shells of the ions.
      The molar entropy of melting of the solvent is used to estimate the amount of
      solvent released in the association process.

PMID- 17228916
TI  - Computational study on the relative acidity of acetic acid by the QM/MM method
      combined with the theory of energy representation.
AB  - We have applied the quantum mechanical/molecular mechanical (QM/MM) method
      combined with the theory of energy representation (ER) to study the acidity of
      acetic acid in aqueous solution. We have focused our attention on the relative
      acidity DeltapK(a) of the molecule with respect to water solvent to circumvent
      the ambiguity of the solvation free energies of the molecular species referred to
      as proton. The value of DeltapK(a) for the acetic acid has been computed as -11.5
      when we adopt the free energy change in the gas phase obtained by the B3LYP
      functional, which is in excellent agreement with the experimental value of -11.0.
      It has been demonstrated that the QM/MM-ER approach recently developed gives an
      adequate description for the solvation free energies related to the
      acidity/basicity calculations of organic molecules.

PMID- 17228917
TI  - Insights into hofmeister mechanisms: anion and degassing effects on the cloud
      point of dioctanoylphosphatidylcholine/water systems.
AB  - Water dispersions of dioctanoylphosphatidylcholine (diC8PC) exhibit upper
      consolute curves. How they are affected by some salts and other additives (D2O,
      urea) has already been explored and the phase separation has been interpreted
      within the framework of the Blankschtein-Thurston-Benedek (BTB) model. This
      deduces the chemical potential gain in micellar growth (Deltamu) and the
      intermicellar interaction coefficient (C) as fitting parameters from the
      coexistence curves. But, the specific mechanisms that drive such phenomena have
      remained obscure. To identify these mechanisms, we investigate the effects of a
      range of anions on the cloud points of diC8PC/H2O systems and extract the
      phenomenological parameters of the BTB model. We show how these parameters, for
      micellar growth, i.e., surface, intramolecular interactions, and for
      interaggregate interactions, i.e., bulk solute effects, are connected to anionic
      polarizabilities. Nonelectrostatic (NES) quantum mechanical fluctuation (Lifshitz
      or dispersion) forces missing from conventional theories are then shown to
      regulate lyotropic Hofmeister effects, both explicitly and implicitly.

PMID- 17228918
TI  - Development of cation/anion "interaction" scales for ionic liquids through ESI-MS
      measurements.
AB  - Electrospray ionization mass spectrometry applied to ionic liquids allowed the
      study of loosely bonded supramolecules, originating from these organic salts.
      Based on the observation that ionic liquids formed cationic [C(q+1)X(q)](+) and
      anionic [C(q)X(q+1)](-) supramolecular aggregates, we have investigated mixed
      networks, formed by different cations coordinated to a selected anion or by
      different anions bonded to a given cation, i.e., [C1...X...C2](+) and
      [X1...C...X2](-), with the aim to build a scale of the cation-anion interaction
      strength. The qualitative order of intrinsic bond strength to Br- was found to be
      the following: [emim](+) > [bmim](+) > [mor1,2](+) > [hmim]+ > [omim](+) >
      [mor1,4](+) > [bupy](+) > [bpyrr](+) > [picol](+) > [bm(2)im](+) > [TBA](+).
      Similarly, the interaction energies to 1-butyl-3-methylimidazolium (bmim) species
      envisaged two classes of anions: species tightly coordinated to the cationic
      moiety that include CF3COO(-), Br(-), N(CN)2(-), and BF4(-) and anions loosely
      interacting with the alkylimidazolium species such as OTf(-), PF6(-), and Tf2N(
      ).

PMID- 17228919
TI  - Thermal denaturation of polyalanine peptide in water by molecular dynamics
      simulations and theoretical prediction of infrared spectra: helix-coil transition
      kinetics.
AB  - Perspectives in the helix-coil transition kinetics of secondary structures are
      examined by temperature-jump molecular dynamics (T-jump MD) simulations and
      theoretically calculated infrared (IR) spectra. Homopolymeric polyalanine, Ac
      (A)(21)-NHMe (A21), is unfolded in water by T-jumps from 273 to 300 K
      approximately 450 K using AMBER ff99 and ff03 force fields. MD simulation results
      provide in silico evidence that 3(10)-helix and type I beta-turn motifs are
      highly probable in both ff99 and ff03 results. Temperature-dependent difference
      IR spectra of A21 do not possess an isosbestic point in both results, and isotope
      labeled difference IR spectra in ff03 results predict characteristic profiles
      observed in experiments. Unfolding rates obtained from simulated time-resoled IR
      spectra are in good agreement with those estimated by helical contents, but they
      are still an order of magnitude smaller than experimental values. We demonstrate
      that the conventional criteria such as single-exponential fit of transient amide
      I absorbance, sigmoidal fit of temperature-dependent amide I absorbance, and
      Arrhenius plot of relaxation rates cannot guarantee the validity of assuming a
      two-state mechanism. We suggest a way of determining T(m) by the temperature
      dependence of center frequency and full width at half-maximum of amide I band.
      Overall, both ff99 and ff03 force fields give consistent results in reproducing
      key aspects concerned experimentally, but are not predominantly satisfactory in
      quantitative aspects.

PMID- 17228921
TI  - On the copper(II) ion coordination by prion protein HGGGW pentapeptide model.
AB  - The interaction of the octapeptide domain of the prion protein with the
      transition-metal-ion Cu2+ was studied at the DFT level by using the HGGGW
      pentapeptide as a model to mimic the PHGGGWGQ octarepeat sequence. Ten complexes,
      in which the metal ion exhibits different coordinations, were considered. Our
      results indicate that the lowest-energy structure is characterized by a
      tetracoordinated metal center and that this tendency of the ion to assume the
      square planar geometry is strong enough to prevent the addition of a further
      water molecule in its coordination sphere. The role of tryptophan was found to
      cause a lowering of the system energy due to the stabilizing effect of the
      electrostatic interaction between the Trp aromatic indole and histidine imidazole
      rings.

PMID- 17228920
TI  - Cytochrome c(2) Exit Strategy: Dissociation Studies and Evolutionary
      Implications.
AB  - Small, water-soluble, type c cytochromes form a transient network connecting
      major bioenergetic membrane protein complexes in both photosynthesis and
      respiration. In the photosynthesis cycle of Rhodobacter sphaeroides, cytochrome
      c2 (cyt c2) docks to the reaction center (RC), undergoes electron transfer, and
      exits for the cytochrome bc1 complex. Translations of cyt c2 about the RC-cyt c2
      docking interface and surrounding membrane reveal possible exit pathways. A
      pathway at a minimal elevation allowed by the architecture of the RC is analyzed
      using both an all-atom steered molecular dynamics simulation of the RC-cyt c2
      complex and a bioinformatic analysis of the structures and sequences of cyt c.
      The structure-based phylogenetic analysis allows for the identification of
      structural elements that have evolved to satisfy the requirements of having
      multiple functional partners. The patterns of evolutionary variation obtained
      from the phylogenetic analysis of both docking partners of cyt c2 reveal
      conservation of key residues involved in the interaction interfaces that would be
      candidates for further experimental studies. Additionally, using the molecular
      mechanics Poisson-Boltzmann surface area method we calculate that the binding
      free energy of reduced cyt c2 to the RC is nearly 6 kcal/mol more favorable than
      with oxidized cyt c2. The redox-dependent variations lead to changes in
      structural flexibility, behavior of the interfacial water molecules, and
      eventually changes in the binding free energy of the complex.

PMID- 17228922
TI  - Hydrogen-bonded nucleic acid base pairs containing unusual base tautomers:
      complete basis set calculations at the MP2 and CCSD(T) levels.
AB  - The total interaction energies of altogether 15 hydrogen-bonded nucleic acid base
      pairs containing unusual base tautomers were calculated. The geometry properties
      of all selected adenine-thymine and guanine-cytosine hydrogen-bonded base pairs
      enable their incorporation into DNA. Unusual base pairing patterns were compared
      with Watson-Crick H-bonded structures of the adenine-thymine and guanine-cytosine
      pairs. The complete basis set (CBS) limit of the MP2 interaction energy and the
      CCSD(T) correction term, determined as the difference between the CCSD(T) and MP2
      interaction energies, was evaluated. Extrapolation to the MP2 CBS limit was done
      using the aug-cc-pVDZ and aug-cc-pVTZ results, and the CCSD(T) correction term
      was determined with the 6-31G*(0.25) basis set. Final interaction energies were
      corrected while taking into account both tautomeric penalization determined at
      the CBS level and solvation/desolvation free energies. The situation for the
      adenine-thymine pairs is straightforward, and tautomeric pairs are significantly
      less stable than the Watson-Crick pair consisting of the canonical forms. In the
      case of the guanine-cytosine pair, the Watson-Crick structure made by canonical
      forms is again the most stable. The other two structures are, however,
      energetically rather similar (by 5 and 6 kcal/mol), which provides a very small
      but non-negligible chance of detecting these structures in the DNA double helix
      (1:5000). Due to the fact that DNA bases and base pairs incorporated into DNA are
      solvated less favorably than in isolated systems, this probability represents the
      very upper limit. The results clearly show how precisely the canonical building
      blocks of DNA molecules were chosen and how well their stability is maintained.

PMID- 17228923
TI  - Effect of glycation on the structure and dynamics of DNA: a critical
      spectroscopic approach.
AB  - Glycated DNA is considered to be a pathogenic factor for diabetes mellitus. Here
      we present a novel and preliminary study on normal and glycated (with fructose
      and glucose-6-phosphate as reducing sugars) human placenta DNA using agarose gel
      electrophoresis and photon correlation spectroscopy. The former is used to find
      structural alterations, while the latter is exploited to observe differences in
      the dynamics between normal (i.e., pure) and glycated DNA molecules. For
      scattering angles up to 90 degrees , we obtained a quasi-single-exponential
      relaxation process for the pure DNA, whereas at higher scattering angles the
      relaxation of pure DNA becomes broader with a stretching parameter beta
      approximately 0.6 at 130 degrees. Interestingly, for both the glycated DNAs
      stretched relaxation profiles and higher relaxation rates (Omega) are observed
      for all scattering angles. Moreover, a separate and very fast relaxation (e.g.,
      relaxation time tau approximately 2 micros at 90 degrees ) can be noticed for
      both the glycated DNAs at all the studied scattering angles. Thus, the dramatic
      changes in the relaxation parameters (Omega, tau, and beta) of the glycated DNA
      show at the molecular level, for the first time, that the structure and dynamics
      of DNA are strongly affected by glycation. Implications of the results are
      discussed.

PMID- 17228924
TI  - Structure-activity relationship of the free-radical-scavenging reaction by
      vitamin E (alpha-, beta-, gamma-, delta-Tocopherols) and ubiquinol-10: pH
      dependence of the reaction rates.
AB  - The reaction rates (ks) of vitamin E (alpha-, beta-, gamma-, delta-tocopherols,
      TocH), ubiquinol-10, and related antioxidants (tocol, ubiquinol-0, and
      hydroquinone) with aroxyl (ArO(.-)) radical have been measured in micellar
      solution by stopped-flow spectrophotometer. The ks values increased in the order
      of hydroquinone < tocol < delta-TocH < ubiquinol-0 < gamma-TocH approximately
      beta-TocH < ubiquinol-10 < alpha-TocH at pH 4 approximately 8. The antioxidants
      which have lower oxidation potentials showed higher reactivities. The ks values
      of alpha-, beta-, gamma-, delta-tocopherol, and tocol remained constant between
      pH 4 and 10, and decreased rapidly at pH 11 approximately 12 by increasing pH
      value. From the pH dependence of ks values, the pKa values (= 13.1 approximately
      12.6) have been determined for these tocopherols. The ks values of ubiquinol-10
      also remained constant between pH 4 and 9, and increased rapidly at pH 9.5.
      Ubiquinol-10 is dibasic acid and can exist in three different molecular forms,
      depending on the pH value. By comparing the ks values with the mole fraction of
      each molecular form of ubiquinol-10, the reaction rate ks1 (= 1.21 x 10(5) M(
      1)s(-1)) for the undissociated form, ks2 (= 1.04 x 10(6) M(-1)s(-1)) for
      monoanion and ks3 (= 0 M(-1)s(-1)) for dianion, and the pKa1 and pKa2 values (=
      11.4 and 12.7) were determined. The ks2 value is 8.6 times as large as the ks1
      value. Similar analyses were performed for ubiquinol-0 and hydroquinone. It was
      found that the relative ratio of ks values (100:21:20:2.9) of alpha-, beta-,
      gamma-, delta-tocopherols in micellar dispersion has good correlation with the
      relative biopotency ratios for rat fetal resorption, rat hemeolysis, and chicken
      muscle dystrophy. The relative antioxidant activities of alpha-tocopherol and
      ubiquinol-10 have been discussed based on the ks values obtained and their
      concentrations in serum and several tissues (heart, muscle, liver, kidney, and
      brain).

PMID- 17228925
TI  - Differential ionic permeation of DNA-modified electrodes.
AB  - Ionic permselectivity of DNA films has been investigated by the analysis of the
      electrochemical response of methylene blue (MB) as a function of pH and ionic
      strength on DNA-modified electrodes in aqueous p-nitrophenol (p-NP) and phosphate
      buffers. We have observed a linear Pourbaix diagram in p-NP buffer indicating
      that the reduction of MB occurs with a two-electron plus one-proton reaction.
      Interestingly, in phosphate buffer the Pourbaix diagram is curved and this
      suggests that the thermodynamics of MB incorporated in the film depend also on
      the ratio of mono- versus divalent anions in the bulk. This result indicates that
      DNA films do not behave as pure ion-exclusion films, but instead there is a
      differential permselectivity that depends on the identity of the anions. Based on
      this consideration of the ionic distribution in the films, we provide a new
      method for the analysis of the DNA surface coverage based on AC impedance of an
      anionic species, ferricyanide. The methodology is of particular value in
      analyzing DNA hybridization and dehybridization. This approach presents an
      advantage compared to standard ruthenium hexammine assays since our methodology
      is insensitive to film morphology, and is highly sensitive to the amount of
      negative charge on the surface.

PMID- 17228926
TI  - Comment on "Analysis on solvated molecules with a new energy partitioning scheme
      for intra- and intermolecular interactions".

PMID- 17228929
TI  - Femtosecond multichannel photodissociation dynamics of CH3I from the A band by
      velocity map imaging.
AB  - The reaction times of several well-defined channels of the C-I bond rupture of
      methyl iodide from the A band, which involves nonadiabatic dynamics yielding
      ground state I(2P3/2) and spin-orbit excited I*(2P1/2) and ground and
      vibrationally excited CH3 fragments, have been measured by a combination of a
      femtosecond laser pump-probe scheme and velocity map imaging techniques using
      resonant detection of ground state CH3 fragments. The reaction times found for
      the different channels studied are directly related with the nonadiabatic nature
      of this multidimensional photodissociation reaction.

PMID- 17228930
TI  - A new glance at HCl-monohydrate spectroscopy, using on-the-fly dynamics.
AB  - On-the-fly dynamics is used to analyze the remarkably anharmonic infrared
      spectroscopy of crystalline HCl monohydrate, an ionic solid composed of H3O+ and
      Cl-. The dominant intense infrared feature is shown to originate from specific
      sections of the hydronium trajectory, in which one of the H-atoms interacts
      strongly with a neighboring Cl-.

PMID- 17228931
TI  - Exciton dissociation at donor-acceptor polymer heterojunctions: quantum
      nonadiabatic dynamics and effective-mode analysis.
AB  - The quantum-dynamical mechanism of photoinduced subpicosecond exciton
      dissociation and the concomitant formation of a charge-separated state at a
      semiconducting polymer heterojunction is elucidated. The analysis is based upon a
      two-state vibronic coupling Hamiltonian including an explicit 24-mode
      representation of a phonon bath comprising high-frequency (C==C stretch) and low
      frequency (torsional) modes. The initial relaxation behavior is characterized by
      coherent oscillations, along with the decay through an extended nonadiabatic
      coupling region. This region is located in the vicinity of a conical intersection
      hypersurface. A central ingredient of the analysis is a novel effective mode
      representation, which highlights the role of the low-frequency modes in the
      nonadiabatic dynamics. Quantum dynamical simulations were carried out using the
      multiconfiguration time-dependent Hartree method.

PMID- 17228932
TI  - Energy quantization of chaos with the semiclassical phases alone.
AB  - The mechanism of energy quantization is studied for classical dynamics on a
      highly anharmonic potential, ranging from integrable, mixed, and chaotic motions.
      The quantum eigenstates (standing waves) are created by the phase factors (the
      action integrals and the Maslov index) irrespective of the integrability, when
      the amplitude factors are relatively slowly varying. Indeed we show numerically
      that the time Fourier transform of an approximate semiclassical correlation
      function in which the amplitude factors are totally removed reproduces the
      spectral positions (energy eigenvalues) accurately in chaotic regime.
      Quantization with the phase information alone brings about dramatic
      simplification to molecular science, since the amplitude factors in the lowest
      order semiclassical approximation diverge exponentially in a chaotic domain.

PMID- 17228933
TI  - A polarizable ion model for the structure of molten AgI.
AB  - The results are reported of the molecular dynamics simulations of the coherent
      static structure factor of molten AgI at 923 K using a polarizable ion model.
      This model is based on a rigid ion potential, to which the many body interactions
      due to the anions induced polarization are added. The calculated structure factor
      is in better agreement with recent neutron diffraction data than that obtained by
      using simple rigid ion pair potentials. The Voronoi-Delaunay method has been
      applied to study the relationship between voids in the spatial distribution of
      cations and the prepeak of the structure factor.

PMID- 17228934
TI  - The spin-orbit transition of atomic chlorine in solid H2, HD, and D2.
AB  - Essential to understanding the reaction dynamics of spin-orbit (SO) excited
      atomic chlorine (2P1/2) with molecular hydrogen is experimental measurements of
      the SO splitting of Cl in the van der Waals region of the entrance channel to
      reaction. Here we report high-resolution direct absorption studies of the SO
      transition (2P1/2<--2P3/2) of atomic chlorine isolated in solid molecular
      hydrogen (H2, HD, and D2).

PMID- 17228935
TI  - Spontaneous liquifaction of isomerizable molecular crystals.
AB  - A lattice vacancy raises the energy of the neighboring (flexible) molecule in a
      crystal, which may be enough to isomerize it to a tautomer that does not fit the
      lattice site, thus creating a liquidlike local region embedding the vacancy.
      Similar regions may appear elsewhere in the lattice and the regions may
      ultimately merge. Thus a crystal may spontaneously liquefy over a period of hours
      to years at a temperature below its normal melting point. Simultaneous heat
      capacity and heat absorption measurements of several such molecular crystals show
      that they spontaneously liquefy at a temperature far below their reputed melting
      point, according to a non-exponential rate kinetics and a temperature dependent
      rate constant, and do not crystallize on cooling.

PMID- 17228936
TI  - Predicted stability and structure of (HXeCCH)n (n=2 or 4) clusters and of
      crystalline HXeCCH.
AB  - Ab initio calculations predict the existence of the dimer and tetramer of HXeCCH.
      The interaction energies are -6.66 and -19.40 kcal mol-1 for the dimer and
      tetramer, respectively. For both complexes, larger blue shifts of the Xe-H
      stretching mode are found, while the Xe-C stretching modes are slightly
      redshifted. The stability and structure of HXeCCH crystals is predicted by
      density functional theory calculations with periodic boundary conditions. Strong
      electrostatic interactions are found between the monomers in the crystal. The
      results are first evidence for the existence of crystalline materials made of a
      novel class of noble gas molecules.

PMID- 17228937
TI  - Calculation of static and dynamic linear magnetic response in approximate time
      dependent density functional theory.
AB  - We report implementations and results of time-dependent density functional
      calculations (i) of the frequency-dependent magnetic dipole-magnetic dipole
      polarizability, (ii) of the (observable) translationally invariant linear
      magnetic response, and (iii) of a linear intensity differential (LID) which
      includes the dynamic dipole magnetizability. The density functional calculations
      utilized density fitting. For achieving gauge-origin independence we have
      employed time-periodic magnetic-field-dependent basis functions as well as the
      dipole velocity gauge, and have included explicit density-fit related derivatives
      of the Coulomb potential. We present the results of calculations of static and
      dynamic magnetic dipole-magnetic dipole polarizabilities for a set of small
      molecules, the LID for the SF6 molecule, and dispersion curves for M-hexahelicene
      of the origin invariant linear magnetic response as well as of three dynamic
      polarizabilities: magnetic dipole-magnetic dipole, electric dipole-electric
      dipole, and electric dipole-magnetic dipole. We have also performed comparison of
      the linear magnetic response and magnetic dipole-magnetic dipole polarizability
      over a wide range of frequencies for H2O and SF6.

PMID- 17228938
TI  - Adiabatic Jacobi corrections for H2+-like systems.
AB  - The Coulomb three-body problem in Jacobi coordinates was solved by treating the
      distance of the particles having equal charge as a parameter. This method allows
      computation of electronic energies with finite nuclear masses while maintaining
      the notion of a potential energy curve. The rotationless ground-state electronic
      and the so-called adiabatic Jacobi correction (AJC) energies are presented for
      H2+, D2+, and HD+ at fixed internuclear separations. The AJCs are defined as the
      difference between the results obtained from calculations using proper finite and
      infinite nuclear masses. Except at the united atom limit, the AJCs are smaller
      than the traditional first-order diagonal Born-Oppenheimer corrections.
      Expectation values of proton-electron, p-e, and deuteron-electron, d-e, distances
      for HD+ have been computed as a function of internuclear separation. Similarly to
      the fully nonadiabatic approach, the present method is able to follow the
      symmetry breaking in HD+. Exact and approximate analytical and numerical results
      are given for counterfactual systems as well. In these cases changes are allowed
      for the values of the electron rest mass or the elementary charge, as well as for
      the mass or charge of the unique particle (electron).

PMID- 17228939
TI  - A coarse graining method for the identification of transition rates between
      molecular conformations.
AB  - The coarse graining method to be advocated in this paper consists of two main
      steps. First, the propagation of an ensemble of molecular states is described as
      a Markov chain by a transition probability matrix in a finite state space.
      Second, we obtain metastable conformations by an aggregation of variables via
      Robust Perron Cluster Analysis (PCCA+). Up to now, it has been an open question
      as to how this coarse graining in space can be transformed to a coarse graining
      of the Markov chain while preserving the essential dynamic information. In this
      article, we construct a coarse matrix that is the correct propagator in the space
      of conformations. This coarse graining procedure carries over to rate matrices
      and allows to extract transition rates between molecular conformations. This
      approach is based on the fact that PCCA+ computes molecular conformations as
      linear combinations of the dominant eigenvectors of the transition matrix.

PMID- 17228940
TI  - High-order electron-correlation methods with scalar relativistic and spin-orbit
      corrections.
AB  - An assortment of computer-generated, parallel-executable programs of ab initio
      electron-correlation methods has been fitted with the ability to use relativistic
      reference wave functions. This has been done on the basis of scalar relativistic
      and spin-orbit effective potentials and by allowing the computer-generated
      programs to handle complex-valued, spinless orbitals determined by these
      potentials. The electron-correlation methods that benefit from this extension are
      high-order coupled-cluster methods (up to quadruple excitation operators) for
      closed- and open-shell species, coupled-cluster methods for excited and ionized
      states (up to quadruples), second-order perturbation corrections to coupled
      cluster methods (up to triples), high-order perturbation corrections to
      configuration-interaction singles, and active-space (multireference) coupled
      cluster methods for the ground, excited, and ionized states (up to active-space
      quadruples). A subset of these methods is used jointly such that the dynamical
      correlation energies and scalar relativistic effects are computed by a lower
      order electron-correlation method with more extensive basis sets and all-electron
      relativistic treatment, whereas the nondynamical correlation energies and spin
      orbit effects are treated by a higher-order electron-correlation method with
      smaller basis sets and relativistic effective potentials. The authors demonstrate
      the utility and efficiency of this composite scheme in chemical simulation
      wherein the consideration of spin-orbit effects is essential: ionization energies
      of rare gases, spectroscopic constants of protonated rare gases, and
      photoelectron spectra of hydrogen halides.

PMID- 17228941
TI  - Molecular properties from variational reduced-density-matrix theory with three
      particle N-representability conditions.
AB  - Molecular ground-state energies and two-electron reduced density matrices (2
      RDMs) have recently been computed without the many-electron wave function by
      constraining the 2-RDM to satisfy a complete set of three-positivity conditions
      for N representability [D. A. Mazziotti, Phys. Rev. A 74, 032501 (2006)].
      Energies at both equilibrium and nonequilibrium geometries are obtained within
      0.3% of the correlation energy. In this paper the authors extend this work to
      examine the accuracy of molecular properties, including multipole moments and
      components of the ground-state energy, relative to full configuration interaction
      (FCI). Comparisons are also made with 2-RDM methods with two-positivity
      conditions and two-positivity plus the generalized T1T2 conditions as well as
      several approximate wave function methods. Using the 2-RDM method with three
      positivity conditions, the authors obtain dipole, quadrupole, and octupole
      moments for BeH2, BH, H2O, CO, and NH3 at equilibrium geometries that are within
      0.04% of their FCI values. In addition, for the potential energy surface of N2,
      the 2-RDM method with three-positivity yields not only accurate total ground
      state energies but also accurate expectation values of the kinetic energy
      operator, the electron-nuclei potential, and electron-electron repulsion.

PMID- 17228942
TI  - Simulated scaling method for localized enhanced sampling and simultaneous
      "alchemical" free energy simulations: a general method for molecular mechanical,
      quantum mechanical, and quantum mechanical/molecular mechanical simulations.
AB  - A potential scaling version of simulated tempering is presented to efficiently
      sample configuration space in a localized region. The present "simulated scaling"
      method is developed with a Wang-Landau type of updating scheme in order to
      quickly flatten the distributions in the scaling parameter lambdam space. This
      proposal is meaningful for a broad range of biophysical problems, in which
      localized sampling is required. Besides its superior capability and robustness in
      localized conformational sampling, this simulated scaling method can also
      naturally lead to efficient "alchemical" free energy predictions when dual
      topology alchemical hybrid potential is applied; thereby simultaneously, both of
      the chemically and conformationally distinct portions of two end point chemical
      states can be efficiently sampled. As demonstrated in this work, the present
      method is also feasible for the quantum mechanical and quantum
      mechanical/molecular mechanical simulations.

PMID- 17228943
TI  - Density functional calculations of NMR shielding tensors for paramagnetic systems
      with arbitrary spin multiplicity: validation on 3d metallocenes.
AB  - The calculation of nuclear shieldings for paramagnetic molecules has been
      implemented in the ReSpect program, which allows the use of modern density
      functional methods with accurate treatments of spin-orbit effects for all
      relevant terms up to order Omicron(alpha4) in the fine structure constant.
      Compared to previous implementations, the methodology has been extended to
      compounds of arbitrary spin multiplicity. Effects of zero-field splittings in
      high-spin systems are approximately accounted for. Validation of the new
      implementation is carried out for the 13C and 1H NMR signal shifts of the 3d
      metallocenes 4VCp2, 3CrCp2, 2MnCp2, 6MnCp2, 2CoCp2, and 3NiCp2. Zero-field
      splitting effects on isotropic shifts tend to be small or negligible. Agreement
      with experimental isotropic shifts is already good with the BP86 gradient
      corrected functional and is further improved by admixture of Hartree-Fock
      exchange in hybrid functionals. Decomposition of the shieldings confirms the
      dominant importance of the Fermi-contact shifts, but contributions from spin
      orbit dependent terms are frequently also non-negligible. Agreement with 13C NMR
      shift tensors from solid-state experiments is of similar quality as for isotropic
      shifts.

PMID- 17228944
TI  - Lorentzian line shape due to an inhomogeneous size distribution without
      relaxation.
AB  - In this paper, it is demonstrated that a Lorentzian line shape is predicted for a
      resonance interacting with a bath of equally spaced levels, even in the sparse,
      low density of states limit, if one performs an inhomogeneous average over the
      position of the bath states relative to the bright state. The implication for the
      spectroscopy of molecules in helium nanodroplets and possibly other samples with
      a significant size distribution is that coupling of excitations to phonons can
      lead to Lorentzian shaped transitions entirely from inhomogeneous broadening with
      no population relaxation in the sample.

PMID- 17228945
TI  - Mass fluctuation kinetics: capturing stochastic effects in systems of chemical
      reactions through coupled mean-variance computations.
AB  - The intrinsic stochastic effects in chemical reactions, and particularly in
      biochemical networks, may result in behaviors significantly different from those
      predicted by deterministic mass action kinetics (MAK). Analyzing stochastic
      effects, however, is often computationally taxing and complex. The authors
      describe here the derivation and application of what they term the mass
      fluctuation kinetics (MFK), a set of deterministic equations to track the means,
      variances, and covariances of the concentrations of the chemical species in the
      system. These equations are obtained by approximating the dynamics of the first
      and second moments of the chemical master equation. Apart from needing knowledge
      of the system volume, the MFK description requires only the same information used
      to specify the MAK model, and is not significantly harder to write down or apply.
      When the effects of fluctuations are negligible, the MFK description typically
      reduces to MAK. The MFK equations are capable of describing the average behavior
      of the network substantially better than MAK, because they incorporate the
      effects of fluctuations on the evolution of the means. They also account for the
      effects of the means on the evolution of the variances and covariances, to
      produce quite accurate uncertainty bands around the average behavior. The MFK
      computations, although approximate, are significantly faster than Monte Carlo
      methods for computing first and second moments in systems of chemical reactions.
      They may therefore be used, perhaps along with a few Monte Carlo simulations of
      sample state trajectories, to efficiently provide a detailed picture of the
      behavior of a chemical system.

PMID- 17228946
TI  - Generation of initial trajectories for transition path sampling of chemical
      reactions with ab initio molecular dynamics.
AB  - Transition path sampling is an innovative method for focusing a molecular
      dynamics simulation on a reactive event. Although transition path sampling
      methods can generate an ensemble of reactive trajectories, an initial reactive
      trajectory must be generated by some other means. In this paper, the authors have
      evaluated three methods for generating initial reactive trajectories for
      transition path sampling with ab initio molecular dynamics. The authors have
      tested each of these methods on a set of chemical reactions involving the
      breaking and making of covalent bonds: the 1,2-hydrogen elimination in the borane
      ammonia adduct, a tautomerization, and the Claisen rearrangement. The first
      method is to initiate trajectories from the potential energy transition state,
      which was effective for all reactions in the test set. Assigning atomic
      velocities found using normal mode analysis greatly improved the success of this
      method. The second method uses a high temperature molecular dynamics simulation
      and then iteratively reduces the total energy of the simulation until a low
      temperature reactive trajectory is found. This was effective in generating a low
      temperature trajectory from an initial trajectory run at 3000 K of the
      tautomerization reaction, although it failed for the other two. The third uses an
      orbital based bias potential to find a reactive trajectory and uses this
      trajectory to initiate an unbiased trajectory. The authors found that a highest
      occupied molecular orbital-lowest unoccupied molecular orbital bias could be used
      to find a reactive trajectory for the Claisen rearrangement, although it failed
      for the other two reactions. These techniques will help make it practical to use
      transition path sampling to study chemical reaction mechanisms that involve bond
      breaking and forming.

PMID- 17228947
TI  - Geometric constraints in semiclassical initial value representation calculations
      in Cartesian coordinates: excited states.
AB  - The authors show that a recently proposed approach [J. Chem. Phys. 123, 084103
      (2005)] for the inclusion of geometric constraints in semiclassical initial value
      representation calculations can be used to obtain excited states of weakly bound
      complexes. Sample calculations are performed for free and constrained rare gas
      clusters. The results show that the proposed approach allows the evaluation of
      excited states with reasonable accuracy when compared to exact basis set
      calculations.

PMID- 17228948
TI  - Imaging the photodissociation of CH3SH in the first and second absorption bands:
      the CH3(X2A1)+SH(X2Pi) channel.
AB  - The CH3(X2A1)+SH(X2Pi) channel of the photodissociation of CH3SH has been
      investigated at several wavelengths in the first 1 1A"<--X 1A' and second 2 1A"<-
      X1A' absorption bands by means of velocity map imaging of the CH3 fragment. A
      fast highly anisotropic (beta=-1+/-0.1) CH3(X2A1) signal has been observed in the
      images at all the photolysis wavelengths studied, which is consistent with a
      direct dissociation process from an electronically excited state by cleavage of
      the C-S bond in the parent molecule. From the analysis of the CH3 images,
      vibrational populations of the SH(X2Pi) counterfragment have been extracted. In
      the second absorption band, the SH fragment is formed with an inverted
      vibrational distribution as a consequence of the forces acting in the crossing
      from the bound 2 1A" second excited state to the unbound 1 1A" first excited
      state. The internal energy of the SH radical increases as the photolysis
      wavelength decreases. In the case of photodissociation via the first excited
      state, the direct production of CH3 leaves the SH counterfragment with little
      internal excitation. Moreover, at the longer photolysis wavelengths corresponding
      to excitation to the 1 1A" state, a slower anisotropic CH3 channel has been
      observed (beta=-0.8+/-0.1) consistent with a two step photodissociation process,
      where the first step corresponds to the production of CH3S(X2E) radicals via
      cleavage of the S-H bond in CH3SH, followed by photodissociation of the nascent
      CH3S radicals yielding CH3(X2A1)+S(X3P0,1,2).

PMID- 17228949
TI  - Theoretical investigation of highly excited vibrational states in DFCO:
      calculation of the out-of-plane bending states and simulation of the
      intramolecular vibrational energy redistribution.
AB  - A previously developed modified Davidson scheme [C. Iung and F. Ribeiro, J. Chem.
      Phys. 121, 174105 (2005)] is applied to compute and analyze highly excited
      (nu2,nu6) eigenstates in DFCO. The present paper is also devoted to the
      simulations of the intramolecular vibrational energy redistribution (IVR)
      initiated by an excitation of the out-of-plane bending vibration (nnu6, n=2,4,6,
      . . . ,18, and 20). The multiconfiguration time-dependent Hartree method is
      exploited to propagate the corresponding six-dimensional wave packets. A
      comprehensive comparison with experimental data as well as with previous
      simulations of IVR in HFCO [G. Pasin et al. J. Chem. Phys. 124, 194304 (2006)] is
      presented.

PMID- 17228950
TI  - Low energy electron energy-loss spectroscopy of CF3X (X=Cl,Br).
AB  - We report threshold electron energy-loss spectra for the fluorohalomethanes CF3X
      (X=Cl,Br). Measurements were made at incident electron energies of 30 and 100 eV
      in energy-loss range of 4-14 eV, and at scattering angles of 4 degrees and 15
      degrees. Several new electronic transitions are observed which are ascribable to
      excitation of low-lying states as well as are intrinsically overlapped in the
      molecules themselves. Assignments of these electronic transitions are suggested.
      These assignments are based on present spectroscopic and cross-section
      measurements, high-energy scattering spectra, and ab initio molecular orbital
      calculations. The calculated potential curves along the C-X bond show repulsive
      nature, suggesting that these transitions may lead to dissociation of the C-X
      bond. The present results are also compared with the previous ones for CF3H, CF4,
      and CF3I.

PMID- 17228951
TI  - Theoretical studies on tunneling ionizations from the doubly degenerate highest
      occupied molecular orbitals of benzene in intense laser fields.
AB  - Combining our generalized Keldysh theory [Sov. Phys. JETP 20, 1307 (1965)] with
      the molecular orbital theory, the authors theoretically study tunneling
      ionizations of neutral benzene in intense linearly polarized Ti:sapphire laser
      fields (800 nm). They consider the ionizations from the highest occupied
      molecular orbitals (HOMOs) of the ground electronic state. The double degeneracy
      of the HOMOs is properly taken into account. In the theory, molecular ionizations
      consist of the individual ionizations from each atom and the quantum
      interferences between them. The theory reproduces the experimental data well. The
      authors also show that the polarization dependence of the ionization rates is
      strongly influenced by the quantum interferences.

PMID- 17228952
TI  - Coulomb explosion of K-shell ionized krypton clusters studied by multiple-ion
      coincidence momentum imaging.
AB  - The Coulomb explosion of K-shell ionized krypton clusters with an average size N
      of 160 has been studied by electron-multiple-ion-coincidence measurements in
      which the time-of-flight (TOF) of ions was measured by using a position sensitive
      detector. The authors have sorted the TOF spectra by the number of coincidence
      ion signals, Ncoin, and found that singly charged fragment ions such as Kr+,
      Kr2+, and Kr3+ are dominant for Ncoin>or=2, and that multiply charged ions are
      detected mainly for Ncoin=1. The Ncoin dependence of the peak widths in the TOF
      spectra reveals that the average momentum of the Kr+ ions increases with Ncoin,
      while those of Kr2+ and Kr3+ decrease. These results have been more directly
      confirmed by the momentum imaging measurements. The authors propose that the
      heavier ions are produced in the central part of clusters where the Coulomb
      interactions from the surrounding ions are more effectively canceled out due to
      the higher symmetry.

PMID- 17228953
TI  - Depolarization ratio of Rayleigh scattered radiation by molecules.
AB  - The depolarization ratios of Rayleigh scattered radiation by molecules has been
      used to measure the ratio of anisotropic polarizability to isotropic (average)
      polarizability in the laboratory. The authors have calculated the depolarization
      ratio for N2, CH3Cl, and H2O from the first principles. It is shown that the
      depolarization ratio derived from input polarizabilities differs by a factor of
      about 4 for 1Sigma diatom N2, by a factor of about 2.9 for symmetric top CH3Cl,
      and by a factor of about 5 for asymmetric top H2O. These large discrepancies
      arise because in deriving the ratio of anisotropic polarizability to isotropic
      (average) polarizability from the measured depolarization ratio, the constraints
      imposed by the conservation of angular momentum have been completely ignored.

PMID- 17228954
TI  - Isomer-specific spectroscopy of the (H2O)8- cluster anion in the intramolecular
      bending region by selective photodepletion of the more weakly electron binding
      species (isomer II).
AB  - The vibrational predissociation spectra of the two more strongly electron binding
      forms of the (H2O)8- anion are obtained in the HOH intramolecular bending region.
      This is accomplished by deconvoluting the overlapping spectra obtained from a
      mixed ensemble using a population modulation scheme in which the low electron
      binding isomer (II) is removed from the ion packet prior to spectroscopic
      analysis. By choosing the energy of the photodepletion laser to lie between the
      vertical detachment energies of the two isomers, the contribution from isomer II
      can be quantitatively eliminated, leaving the population of I largely unaffected.
      The low binding energies involved in the application of the method to the water
      cluster anions necessitate that this should be carried out in the midinfrared,
      thus requiring two tunable ir laser systems for implementation. The isolated
      spectrum of isomer 1 displays a strong, redshifted feature associated with a
      double H-bond acceptor (AA) water molecule in direct contact with the excess
      electron and a large gap before higher energy features appear that are typically
      associated with (acceptor/donor) AD and ADD binding sites in the network. The
      more weakly binding isomer II does not display the AA feature and instead
      contributes broad structure at intermediate redshifts that merges with the region
      associated with neutral water cluster networks.

PMID- 17228955
TI  - The ground state tunneling splitting and the zero point energy of malonaldehyde:
      a quantum Monte Carlo determination.
AB  - Quantum dynamics calculations of the ground state tunneling splitting and of the
      zero point energy of malonaldehyde on the full dimensional potential energy
      surface proposed by Yagi et al. [J. Chem. Phys. 1154, 10647 (2001)] are reported.
      The exact diffusion Monte Carlo and the projection operator imaginary time
      spectral evolution methods are used to compute accurate benchmark results for
      this 21-dimensional ab initio potential energy surface. A tunneling splitting of
      25.7+/-0.3 cm-1 is obtained, and the vibrational ground state energy is found to
      be 15 122+/-4 cm-1. Isotopic substitution of the tunneling hydrogen modifies the
      tunneling splitting down to 3.21+/-0.09 cm-1 and the vibrational ground state
      energy to 14 385+/-2 cm-1. The computed tunneling splittings are slightly higher
      than the experimental values as expected from the potential energy surface which
      slightly underestimates the barrier height, and they are slightly lower than the
      results from the instanton theory obtained using the same potential energy
      surface.

PMID- 17228956
TI  - Sequential addition of H2O, CH3OH, and NH3 to Al3O3-: a theoretical study.
AB  - Photoelectron spectra of two species, Al3O3(H2O)2- and Al3O3(CH3OH)2-, that are
      produced by the addition of two water or methanol molecules to Al3O3- are
      interpreted with density-functional geometry optimizations and electron
      propagator calculations of vertical electron detachment energies. In both cases,
      there is only one isomer that is responsible for the observed spectral features.
      A high barrier to the addition of a second molecule may impede the formation of
      Al3O3N2H6- clusters in an analogous experiment with NH3.

PMID- 17228957
TI  - Ab initio molecular dynamics study of manganese porphine hydration and
      interaction with nitric oxide.
AB  - The authors use ab initio molecular dynamics and the density functional theory+U
      (DFT+U) method to compute the hydration environment of the manganese ion in
      manganese (II) and manganese (III) porphines (MnP) dispersed in liquid water.
      These are intended as simple models for more complex water soluble porphyrins,
      which have important physiological and electrochemical applications. The
      manganese ion in Mn(II)P exhibits significant out-of-porphine plane displacement
      and binds strongly to a single H2O molecule in liquid water. The Mn in Mn(III)P
      is on average coplanar with the porphine plane and forms a stable complex with
      two H2O molecules. The residence times of these water molecules exceed 15 ps. The
      DFT+U method correctly predicts that water displaces NO from Mn(III)P-NO, but
      yields an ambiguous spin state for the MnP(II)-NO complex.

PMID- 17228958
TI  - Effect of nuclear motion on the absorption spectrum of dipicolinic acid.
AB  - Using semiclassical electron-radiation-ion dynamics, the authors have examined
      the effect of nuclear motion, resulting from both finite temperature and the
      response to a radiation field, on the line broadening of the excitation profile
      of 2,6-pyridinedicarboxylic acid (dipicolinic acid). With nuclei fixed, there is
      a relatively small broadening associated with the finite time duration of an
      applied laser pulse. When the nuclei are allowed to move, the excitation spectrum
      exhibits a much larger broadening, and is also reduced in height and shifted
      toward lower frequencies. In both cases, the excitation is due to well-defined pi
      to pi* transitions. The further inclusion of thermal motion at room temperature
      broadens the linewidth considerably because of variations in the molecular
      geometry: Transitions that had zero or negligible transition probabilities in the
      ground state geometry are weakly excited at room temperature.

PMID- 17228959
TI  - Phase diagrams of alkali halides using two interaction models: a molecular
      dynamics and free energy study.
AB  - Phase diagrams for potassium and sodium chlorides are determined by molecular
      dynamics and free energy calculations. Two rigid-ion interaction models, namely,
      the Born-Mayer-Huggins (BMH) and Michielsen-Woerlee-Graaf (MWG) effective pair
      potentials, have been used. The critical and triple point properties are
      discussed and compared with available experimental and simulation data. The MWG
      model reproduces the experimental liquid-gas equilibria better than the BMH
      model, being the accordance very good in the lowest temperature region of the
      coexistent liquids, particularly for NaCl. However, both models underestimate the
      critical temperatures of KCl and NaCl. Relatively to the solid-gas equilibria,
      the models do not reproduce well the experimental data. As for the solid-liquid
      coexistences either the BMH or the MWG models appear unrealistic.

PMID- 17228961
TI  - Surface tension and vapor-liquid phase coexistence of confined square-well fluid.
AB  - Phase equilibria of a square-well fluid in planar slit pores with varying slit
      width are investigated by applying the grand-canonical transition-matrix Monte
      Carlo (GC-TMMC) with the histogram-reweighting method. The wall-fluid interaction
      strength was varied from repulsive to attractive such that it is greater than the
      fluid-fluid interaction strength. The nature of the phase coexistence envelope is
      in agreement with that given in literature. The surface tension of the vapor
      liquid interface is calculated via molecular dynamics simulations. GC-TMMC with
      finite size scaling is also used to calculate the surface tension. The results
      from molecular dynamics and GC-TMMC methods are in very good mutual agreement.
      The vapor-liquid surface tension, under confinement, was found to be lower than
      the bulk surface tension. However, with the increase of the slit width the
      surface tension increases. For the case of a square-well fluid in an attractive
      planar slit pore, the vapor-liquid surface tension exhibits a maximum with
      respect to wall-fluid interaction energy. We also report estimates of critical
      properties of confined fluids via the rectilinear diameter approach.

PMID- 17228960
TI  - Electron photoemission from charged films: absolute cross section for trapping 0
      5 eV electrons in condensed CO2.
AB  - The electron trapping or attachment cross section of carbon dioxide (CO2)
      condensed as thin films on a spacer of Ar is obtained using a simple model for
      electron trapping in a molecular film and then charge releasing from the same
      film by photon absorption. The measurements are presented for different electron
      exposures and impact energies, film thicknesses, and probing photon energies. The
      cross section for trapping an electron of incident energy between 0 and 5 eV
      reveals three different attachment processes characterized by a maximum at about
      0.75 eV, a structured feature around 2.25 eV, and a shoulder around 3.75 eV. From
      the measurement of their dependence with the probing photon energy, the two
      lowest processes produce traps having a vertical electron binding energy of
      approximately 3.5 eV, whereas the highest one yields a slightly higher value of
      approximately 3.7 eV. The 0.75 eV maximum corresponds to the formation of
      vibrational Feshbach resonances in (CO2)n- anion clusters. The 2.25 eV feature is
      attributed to the formation of a vibrationally excited 2Piu anion in (CO2)n-
      clusters, followed by fast decay into its vibrational ground state without
      undergoing autodetachment. Finally, 3.75 eV shoulder is assigned to the well
      known dissociative electron attachment process from 2Piu anion state producing
      the O- anion in the gas phase and the (CO2)nO- anions in clusters.

PMID- 17228962
TI  - Water adsorption in ion-bearing nanopores.
AB  - Grand canonical Monte Carlo simulations are used to examine the adsorption of
      water into cylindrical nanopores containing single ions. The isotherms for water
      adsorbing into nanopores with radii of 0.44, 0.54, 0.64, and 0.74 nm and
      containing Na+, K+, Ca2+, Cl-, or F- at 298 K are computed. In all cases the
      nanopores are found to fill at reservoir chemical potentials below the chemical
      potential of saturated water vapor at 298 K. The threshold chemical potential is
      found to be sensitive to both the size of the channel and the ion species, with
      the anion-bearing pores filling at lower chemical potentials. Additionally, the
      filling threshold chemical potential is found to decrease as the radius of the
      pores is decreased. Pores with K+ and Cl- are compared, and the Cl- pores are
      found to exhibit higher water densities in the filled states and a more
      energetically favorable water structure while yielding lower per particle
      entropies. Sample simulation configurations are also examined and indicate that
      at low chemical potentials, the adsorbed water forms a cluster around the ion.
      Finally, the influence of the choice of water model on the adsorption isotherms
      is examined.

PMID- 17228963
TI  - Electronic characteristics of fluorene/TiO2 molecular heterojunctions.
AB  - The electronic properties of molecular junctions of the general type
      carbon/molecule/TiO2Au were examined as examples of "molecular heterojunctions"
      consisting of a molecular monolayer and a semiconducting oxide. Junctions
      containing fluorene bonded to pyrolyzed photoresist film (PPF) were compared to
      those containing Al2O3 instead of fluorene, and those with only the TiO2 layer.
      The responses to voltage sweep and pulse stimulation were strongly dependent on
      junction composition and temperature. A transient current response lasting a few
      milliseconds results from injection and trapping of electrons in the TiO2 layer,
      and occurred in all three junction types studied. Conduction in PPFTiO2Au
      junctions is consistent with space charge limited conduction at low voltage, then
      a sharp increase in current once the space charge fills all the traps. With
      fluorene present, there is a slower, persistent change in junction conductance
      which may be removed by a reverse polarity pulse. This "memory" effect is
      attributed to a redox process in the TiO2 which generates TiIII and/or TiII,
      which have much higher conductance than TiO2 due to the presence of conduction
      band electrons. The redox process amounts to "dynamic doping" of the TiO2 layer
      by the imposed electric field. The memory effect arises from a combination of the
      properties of the molecular and oxide layers, and is a special property of the
      molecular heterojunction configuration.

PMID- 17228964
TI  - Nonlinear signal mixing in a three-terminal molecular wire.
AB  - The authors study the electronic response of two simple molecular devices to a
      bichromatic field, where the device acts as a mixer. Two closely related model
      systems are considered: one is a benzene molecule and the other is a single
      grapheme sheet, and in both cases the systems are connected to three
      polyacetylene chains. The electronic response to the dichromatic alternating
      electric fields is studied by following the electron density fluctuation along
      the chain lengths. In both cases the electron transfer follows the field
      frequency at low electric fields. At higher amplitude, a significant amount of
      nonlinear mixing resulting in new combinations of the input frequencies is found
      in the spectrum. The influence of gating on the output frequencies is also shown.

PMID- 17228965
TI  - Vapor phase nucleation on neutral and charged nanoparticles: condensation of
      supersaturated trifluoroethanol on Mg nanoparticles.
AB  - A new technique is described to study the condensation of supersaturated vapors
      on nanoparticles under well-defined conditions of vapor supersaturation,
      temperature, and carrier gas pressure. The method is applied to the condensation
      of supersaturated trifluoroethanol (TFE) vapor on Mg nanoparticles. The
      nanoparticles can be activated to act as condensation nuclei at supersaturations
      significantly lower than those required for homogeneous nucleation. The number of
      activated nanoparticles increases with increasing the vapor supersaturation. The
      small difference observed in the number of droplets formed on positively and
      negatively charged nanoparticles is attributed to the difference in the
      mobilities of these nanoparticles. Therefore, no significant charge preference is
      observed for the condensation of TFE vapor on the Mg nanoparticles.

PMID- 17228966
TI  - The determination of an inhomogeneous linewidth for a strongly coupled adsorbate
      system.
AB  - We present a set of experiments that provide a complete mapping of coherent and
      incoherent vibrational relaxation times for a molecule on a metal surface,
      CO/Ir{111}. Included is the first detection of a midinfrared photon echo from a
      metallic surface, some 15 years after the analogous measurement on a
      semiconductor surface, which sets a precedent for the ability to manipulate and
      rephase polarization on a subpicosecond time scale on surfaces. For the C-O
      stretch in a strongly dipole-coupled CO layer we obtain a total linewidth of 5.6
      cm-1, composed of a homogeneous width of 2.7 cm-1 and an inhomogeneous
      contribution of 3.0 cm-1. Pure dephasing is negligible at liquid nitrogen
      temperatures, making CO/Ir{111} an attractive model system for quantum computing.

PMID- 17228967
TI  - Phenomenological theory of the nematic to lamellar phase transition in lyotropic
      liquid crystals.
AB  - A phenomenological theory is presented to describe the nematic to lamellar phase
      transition in lyotropic liquid crystals. The problem of the first or second order
      transition is explored by means of the variation of the surfactant concentration.
      The possibility of the tricritical point at the nematic to lamellar phase
      transition is discussed in a phenomenological way. The influence of the
      electrolyte on this transition is also discussed by varying the coupling between
      the electrolyte concentration variables and the order parameters. The theoretical
      prediction is found to be in good qualitative agreement with experimental
      results.

PMID- 17228968
TI  - Polyion-induced liposomal vesicle aggregation: a radiowave dielectric relaxation
      study.
AB  - The radiowave dielectric properties of aqueous heterogeneous systems during the
      complexation of charged polyions and oppositely charged liposomal particles have
      been measured in a wide frequency range, between 100 Hz and 2 GHz. The formation
      of a polyion-liposome complex driven by the correlated polyion adsorption at the
      particle surface implies two concomitant effects referred to as reentrant
      condensation and charge inversion. Both of them are governed by electrostatic
      interactions and there is now strong evidence, based on experiments and
      simulations, that counterion release is the driving force of the aggregation
      process. From this point of view, dielectric technique may offer a suitable tool
      in the investigation of the structural properties of these aggregates. In spite
      of the fact that interaction of polyions with oppositely charged surfaces was
      extensively experimentally investigated, there are no papers concerning the
      dielectric properties during the polyion-induced aggregation. To get an insight
      into this important topic, the authors present here an extensive set of radiowave
      dielectric measurements of liposomal vesicle aqueous suspensions where the
      liposome aggregation was induced by an oppositely charged polyion. The
      aggregation was followed from the beginning, when most of the isolated liposomes
      predominate, up to the formation of polyion-coated liposomes of inverted charge,
      crossing the isoelectric condition, where large, almost neutral, aggregates
      appear. The authors describe the observed dielectric dispersions as due to
      counterion polarization in the adjacency of the liposome and liposome aggregate
      surface, primarily governed by the zeta potential, according to the standard
      electrokinetic model.

PMID- 17228969
TI  - Symmetric diblock copolymers in nanopores: Monte Carlo simulations and strong
      stretching theory.
AB  - We have performed lattice Monte Carlo simulations to study the self-assembled
      morphology of symmetric diblock copolymers in nanopores. The pore diameter and
      surface preference are systematically varied to examine their effects on the
      chain conformations, structures of various morphologies, and their phase
      transition. Various ensemble-averaged profiles and quantities are used to provide
      detailed information about the system. The simulation results are also compared
      with the predictions of a strong-stretching theory commonly used in the
      literature. Such comparisons reveal the deficiencies of this theory in describing
      the morphologies under cylindrical confinement, and call for further theoretical
      studies using more accurate formalisms.

PMID- 17228971
TI  - Negative compressibility and nonequivalence of two statistical ensembles in the
      escape transition of a polymer chain.
AB  - An end-tethered polymer chain compressed between two pistons undergoes an abrupt
      transition from a confined coil state to an inhomogeneous flowerlike conformation
      partially escaped from the gap. This phase transition is first order in the
      thermodynamic limit of infinitely long chains. A rigorous analytical theory is
      presented for a Gaussian chain in two ensembles: (a) the H-ensemble, in which the
      distance H between the pistons plays the role of the independent control
      parameter, and (b) the conjugate f-ensemble, in which the external compression
      force f is the independent parameter. Details about the metastable chain
      configurations are analyzed by introducing the Landau free energy as a function
      of the chain stretching order parameter. The binodal and spinodal lines, as well
      as the barrier heights between the stable and metastable states in the free
      energy landscape, are presented in both ensembles. In the loop region for the
      average force with dependence on the distance H (i.e., in the H-ensemble) a
      negative compressibility exists, whereas in the f-ensemble the average distance
      as a function of the force is strictly monotonic. The average fraction of
      imprisoned segments and the lateral force, taken as functions of the distance H
      or the average H, respectively, have different behaviors in the two ensembles.
      These results demonstrate a clear counterexample of a main principle of
      statistical mechanics, stating that all ensembles are equivalent in the
      thermodynamic limit. The authors show that the negative compressibility in the
      escape transition is a purely equilibrium result and analyze in detail the origin
      of the nonequivalence of the ensembles. It is argued that it should be possible
      to employ the escape transition and its anomalous behavior in macroscopically
      homogeneous, but microscopically inhomogeneous, materials.

PMID- 17228970
TI  - Morphology of a highly asymmetric double crystallizable poly(epsilon-caprolactone
      b-ethylene oxide) block copolymer.
AB  - The morphology of a highly asymmetric double crystallizable poly(epsilon
      caprolactone-b-ethylene oxide) (PCL-b-PEO) block copolymer has been studied with
      in situ simultaneously small and wide-angle x-ray scattering as well as atomic
      force microscopy. The molecular masses Mn of the PCL and PEO blocks are 24,000
      and 5800, respectively. X-ray scattering and rheological measurements indicate
      that no microphase separation occurs in the melt. Decreasing the temperature
      simultaneously triggers off a crystallization of PCL and microphase separation
      between the PCL and PEO blocks. Coupling and competition between microphase
      separation and crystallization results in a morphology of PEO spheres surrounded
      by PCL partially crystallized in lamella. Further decreasing temperature induces
      the crystallization of PEO spheres, which have a preferred orientation due to the
      confinements from hard PCL crystalline lamella and from soft amorphous PCL
      segments in different sides. The final morphology of this highly asymmetric block
      copolymer is similar to the granular morphology reported for syndiotactic
      polypropylene and other (co-) polymers. This implies a similar underlying
      mechanism of coupling and competition of various phase transitions, which is
      worth further exploration.

PMID- 17228972
TI  - Effect of free volume and temperature on the structural relaxation in
      polymethylphenylsiloxane: a positron lifetime and pressure-volume-temperature
      study.
AB  - The microstructure of the free volume and its temperature dependence in
      polymethylphenylsiloxane (PMPS) have been examined using positron annihilation
      lifetime spectroscopy (PALS) and pressure-volume-temperature experiments. The
      hole-free volume fraction h and the specific hole-free and occupied volumes,
      Vf=hV and Vocc=(1-h)V, were estimated employing the Simha-Somcynsky (SS) lattice
      hole theory. From the PALS spectra analyzed with the new routine LT9.0 the hole
      size distribution, its mean, <nuh>, and mean dispersion, sigmah, were calculated.
      A comparison of <nuh> with V and Vf delivered a constant specific hole number
      Nh'. Using a fluctuation approach the temperature dependency of the volume of the
      smallest representative freely fluctuating subsystem, <VSV>, is estimated to vary
      from approximately 8.5 nm3 at Tg to approximately 3 nm3 at T/Tg>or=1.15. Unlike
      other polymers, the segmental relaxation from dielectric spectroscopy of PMPS
      follows the Cohen-Turnbull free volume theory almost perfectly in the temperature
      and pressure ranges between 243 and 279 K and 0 and approximately 100 MPa. This
      behavior correlates with the small mass of the SS lattice mer which indicates the
      high flexibility of the PMPS chain. Above 293 K and approximately 150 MPa, the
      free volume prediction gives relaxation times that are too small, which indicates
      that effects of thermal energy must be included in the analysis. To quantify the
      degree to which volume and thermal energy govern the structural dynamics the
      ratio of the activation enthalpies, Ei=R[(d ln taudT1)]i (tau-relaxation time of
      alpha relaxation), at constant volume V and constant pressure P, EV/EP, is
      frequently determined. The authors present arguments for necessity to substitute
      EV with EVf, the activation enthalpy at constant (hole) free volume, and show
      that EVf/EP changes as expected: increasing with increasing free volume, i.e.,
      with increasing temperature and decreasing pressure. EVf/EP (=0.04-0.1) exhibits
      remarkably smaller values than EV/EP (=0.44-0.53), which leads to the inference
      that the free volume plays a distinctly larger role in dynamics than
      traditionally concluded from EV/EP. This conclusion is in agreement with the
      results of our more direct Cohen-Turnbull free volume analysis.

PMID- 17228973
TI  - Rheology of a reversible supramolecular polymer studied by comparison of the
      effects of temperature and chain stoppers.
AB  - The rheology of a reversible supramolecular polymer is studied by comparing the
      effects of an increase in temperature and the addition of chain stoppers. The
      dependence of the zero-shear viscosity and the terminal relaxation time on
      temperature is exponential, and the activation energy for viscous flow can be
      calculated. Above a critical stopper fraction, power laws describe the stopper
      dependence of the viscosity and relaxation time. A simple model for the effect of
      the addition of chain stoppers on the average degree of polymerization adequately
      describes the results. A comparison of flow curves at several temperatures and
      stopper fractions reveals considerable differences between solutions with the
      same zero-shear viscosity. These are mainly associated with differences in the
      terminal relaxation time. A mechanism of shear-induced alignment and subsequent
      elongation of chains is proposed, with which the experimental results are
      consistent.

PMID- 17228974
TI  - Actin polymerization under pressure: a theoretical study.
AB  - An extended Flory-Huggins-type equilibrium polymerization theory for compressible
      systems is used to describe experimental data for the unusual pressure and
      temperature dependence of the equilibrium polymerization of G-actin to F-actin.
      The calculations provide rich insights into the reaction mechanism and the
      thermodynamics of actin polymerization at the molecular level. Volume changes
      associated with individual steps of the mechanism are calculated to be
      DeltaVactiv=(s1*-s1)upsilon0=+1553 mlmol for the activation reaction,
      DeltaVdim=(s2-s1*)upsilon0=-3810 mlmol for dimerization, and DeltaVprop=(sP
      s1)upsilon0=+361 mlmol for the propagation reaction, where s1upsilon0,
      s1*upsilon0, s2upsilon0, and sPupsilon0 are the monomer volumes in the G-actin
      monomer, the activated G-action, the dimer, and higher polymers, respectively.
      Comparison with experimental measurements is made, and discrepancies are
      discussed.

PMID- 17228975
TI  - Coarse-grained protein molecular dynamics simulations.
AB  - A limiting factor in biological science is the time-scale gap between
      experimental and computational trajectories. At this point, all-atom explicit
      solvent molecular dynamics (MD) are clearly too expensive to explore long-range
      protein motions and extract accurate thermodynamics of proteins in isolated or
      multimeric forms. To reach the appropriate time scale, we must then resort to
      coarse graining. Here we couple the coarse-grained OPEP model, which has already
      been used with activated methods, to MD simulations. Two test cases are studied:
      the stability of three proteins around their experimental structures and the
      aggregation mechanisms of the Alzheimer's Abeta16-22 peptides. We find that
      coarse-grained isolated proteins are stable at room temperature within 50 ns time
      scale. Based on two 220 ns trajectories starting from disordered chains, we find
      that four Abeta16-22 peptides can form a three-stranded beta sheet. We also
      demonstrate that the reptation move of one chain over the others, first observed
      using the activation-relaxation technique, is a kinetically important mechanism
      during aggregation. These results show that MD-OPEP is a particularly appropriate
      tool to study qualitatively the dynamics of long biological processes and the
      thermodynamics of molecular assemblies.

PMID- 17228976
TI  - Large two-photon absorptivity of hemoglobin in the infrared range of 780-880 nm.
AB  - Porphyrin molecules have a highly conjugated cyclic structure and are theorized
      to have unusually large two-photon absorptivities (sigmaTPA), i.e., sigmaTPA
      approximately 10(2) GM. The authors tested this claim. Ultrafast two-photon
      absorption (TPA) spectroscopy was performed on solutions of hemoglobin, which
      contains a naturally occurring metaloporphyrin. They used a pump-probe technique
      to directly detect the change in transmission induced by TPA over the wavelength
      range of lambda0=780-880 nm. As controls, they measured the TPA of the dyes
      rhodamine 6G and B; their measurements both verify and extend previously reported
      values. In new results, hemoglobin was found to have a peak two-photon
      absorptivity of sigmaTPA approximately 150 GM at lambda0=825 nm, near a resonance
      of the Soret band. This value supports theoretical expectations. They also found
      a significant difference in the TPA of carboxyhemoglobin versus oxyhemoglobin,
      e.g., sigmaTPA=61 GM versus sigmaTPA=18 GM, respectively, at lambda0=850 nm,
      which shows that the ligand affects the electronic states involved in TPA.

PMID- 17228977
TI  - Rank-ordering protein-ligand binding affinity by a quantum mechanics/molecular
      mechanics/Poisson-Boltzmann-surface area model.

PMID- 17228978
TI  - Comment on "ab initio studies of (H2O)14- clusters: existence of surface and
      interior-bound extra electrons" [J. Chem. Phys. 125, 024307 (2006)].

PMID- 17228985
TI  - Work-family conflicts and self-rated health among middle-aged municipal employees
      in Finland.
AB  - Work-family conflicts are common, but their effects on health are not well known.
      The aim of this study was to examine the associations between work-family
      conflicts and self-rated health among middle-aged municipal employees. In
      addition, the effect of social background factors on the association between work
      family conflicts and self-rated health were examined. The data were based on
      cross-sectional postal surveys, which were carried out in 2001 and 2002, among
      female and male employees of the city of Helsinki, Finland. The participants were
      aged 40-60, and the response rate for women was 69%, and for men 60%. In the
      final analysis, 3,443 women and 875 men were included. For men and woman alike,
      work-to-family and family-to-work conflicts were associated with poor self-rated
      health. The association remained after adjusting for sociodemographic and
      socioeconomic factors. This study shows that a better balance between family life
      and work outside the home would probably have a health promoting effect.

PMID- 17228986
TI  - Benefits of the uncertainty management intervention for African American and
      White older breast cancer survivors: 20-month outcomes.
AB  - In a 2 x 2 randomized block repeated measure design, this study evaluated the
      follow-up efficacy of the uncertainty management intervention at 20 months. The
      sample included 483 recurrence-free women (342 White, 141 African American women;
      mean age = 64 years) who were 5-9 years posttreatment for breast cancer. Women
      were randomly assigned to either the intervention or usual care control
      condition. The intervention was delivered during 4 weekly telephone sessions in
      which survivors were guided in the use of audiotaped cognitive-behavioral
      strategies and a self-help manual. Repeated measures MANOVAs evaluating treatment
      group, ethnic group, and treatment by ethnic interaction effects at 20 months
      indicated that training in uncertainty management resulted in improvements in
      cognitive reframing, cancer knowledge, and a variety of coping skills.
      Importantly, the 20-month outcomes also demonstrated benefits for women in the
      intervention condition in terms of declines in illness uncertainty and stable
      effects in personal growth over time.

PMID- 17228987
TI  - Understanding exercise behavior among Korean adults: a test of the
      transtheoretical model.
AB  - The purpose of this study was to examine the theorized association of
      Transtheoretical Model (TTM) of behavior change constructs by stage of change for
      exercise behavior among Korean adults. A total of 1,335 Korean adults were
      recruited and surveyed from the Nowon district, geographically located in
      northern Seoul. Four Korean-version questionnaires were used to identify the
      stage of exercise behavior and psychological attributes of adolescents. Data were
      analyzed by frequency analysis, MANOVA, correlation analysis, and discriminant
      analysis. Multivariate F tests indicated that behavioral and cognitive processes
      of change, exercise efficacy, and pros differentiated participants across the
      stages of exercise behavior. Furthermore, the findings revealed that adults'
      exercise behavior was significantly correlated with the TTM constructs and that
      overall classification accuracy across the stages of change was 50.6%. This study
      supports the internal and external validity of the TTM for explaining exercise
      behavior.

PMID- 17228989
TI  - Feasibility of an electronic diary in clinical burnout.
AB  - Electronic diaries overcome important drawbacks of retrospective reports and
      capture fluctuations of psychological states and behavior. This study represents
      the first use of this method in clinically burned-out participants and aims to
      establish its feasibility concerning participant acceptability, compliance, and
      reactivity in this sample. Electronic diary measurement of burnout symptoms was
      performed 5 times a day for 2 weeks in 60 burned-out participants on sick leave
      and in 40 healthy controls. The method was well accepted, compliance was high
      (81%-96%), and no reactivity effect was found on the recording of burnout
      symptoms. We conclude that the electronic diary employed is accurate, reliable,
      and a promising tool in capturing key symptoms and their fluctuations in clinical
      burnout.

PMID- 17228988
TI  - Efficacy of a computer-based hearing test and tailored hearing protection
      intervention.
AB  - Advances in computer technology and accessibility enable researchers to provide
      individually tailored interventions for behavioral change. Using multimedia
      technology, this study developed and tested a computer-based hearing test and a
      tailored intervention. The purpose of this study was to evaluate, using a
      randomized experimental design, the efficacy of the intervention to increase
      workers' use of hearing protection. The tailored intervention developed by the
      research team showed more significant short-term effect measured immediately
      after the intervention than the control intervention. For the long-term effect
      measured 1 year after the intervention, both tailored and control groups showed
      significant increase in their reported use (7% vs. 6%) from preintervention to
      postintervention, but no significant difference between the two groups. The
      change accomplished in this study was small progress toward the desired level of
      100% use of hearing protection to prevent noise-induced hearing loss. This
      finding showed that changing workers' hearing protection behavior is difficult.

PMID- 17228990
TI  - The relationship between parenting dimensions and adult achievement: evidence
      from the Whitehall II Study.
AB  - This article examines the association between three dimensions of perceived
      parenting--warmth, strictness, and expectation--and adult cognitive and
      socioeconomic achievement outcomes. Structural equation models (N = 7,035) were
      used to examine simultaneously the influence of parenting on adult achievement
      while controlling for the influence of parental socioeconomic circumstances. Very
      low and very high level of parental warmth was associated with poor adult
      achievement. Strictness had a negative and parental expectation a positive
      relationship with adult achievement. These associations were independent of
      parental socioeconomic circumstances. Own education was found to mediate 27-56%
      of the relationship between parenting dimensions and adult achievement. Parental
      expectation was most strongly related to adult achievement. We conclude that
      parenting plays a significant role in the development of adult achievement: both
      cognitive ability and socioeconomic achievement. Moderate levels of warmth, low
      levels of strictness, and high parental expectation are associated with high
      adult achievement.

PMID- 17228991
TI  - Effects of expectation and caffeine on arousal, well-being, and reaction time.
AB  - The objective of this study is to determine the impact of expectation associated
      with placebo and caffeine ingestion. We used a three-armed, randomized, double
      blind design. Two three-armed experiments varying instruction (true, false,
      control) investigated the role of expectations of changes in arousal (blood
      pressure, heart rate), subjective well-being, and reaction time (RT). In
      Experiment 1 (N = 45), decaffeinated coffee was administered, and expectations
      were produced in one group by making them believe they had ingested caffeinated
      coffee. In Experiment 2 (N = 45), caffeinated orange juice was given in both
      experimental groups, but only one was informed about the true content. In
      Experiment 1, a significant effect for subjective alertness was found in the
      placebo treatment compared to the control group. However, for RT and well-being
      no significant effects were found. In Experiment 2, no significant expectancy
      effects were found. Caffeine produced large effects for blood pressure in both
      treatments compared to the control group, but the effects were larger for the
      false information group. For subjective well-being (alertness, calmness),
      considerable but nonsignificant changes were found for correctly informed
      participants, indicating possible additivity of pharmacologic effect and
      expectations. The results tentatively indicate that placebo and expectancy
      effects primarily show through introspection.

PMID- 17228992
TI  - Social support and behavior in a stressful situation in relation to myocardial
      infarction and mortality: who is at risk? Results from prospective cohort study
      "Men born in 1914," Malmo, Sweden.
AB  - Coronary heart disease remains an important cause of morbidity and mortality.
      Much data support the view that social support is associated with coronary heart
      disease. Participants of the study "Men born in 1914," (414 men) were followed
      from a baseline measurement in 1982/83 until the end of 1996. At baseline, the
      men answered a questionnaire on social support and participated in a stressful
      test where their behavior was categorized as adaptive or maladaptive. This study
      examined whether social support had a prospective impact on the incidence of
      myocardial infarction and all-cause mortality when behavior in the stressful task
      was taken into consideration. The conclusion of the study was that unsatisfactory
      levels of social support is associated with an increased risk of incident
      myocardial infarction (HR 2.40, CI 1.36-4.25, p = .003) and premature death (HR
      1.99, CI 1.32-3.00, p = .001) but only in men who had shown maladaptive behavior
      in the test.

PMID- 17228993
TI  - Small-diameter porous poly (epsilon-caprolactone) films enhance adhesion and
      growth of human cultured epidermal keratinocyte and dermal fibroblast cells.
AB  - Autologous keratinocyte grafts provide clinical benefit by rapidly covering
      wounded areas, but they are fragile. We therefore developed biocompatible
      hexagonal-packed porous films with uniform, circular pore sizes to support human
      keratinocytes and fibroblasts. Cells were cultured on these porous poly (epsilon
      calprolactone) films with pore sizes ranging from novel ultra-small 3 microm to
      20 microm. These were compared with flat (pore-less) films. Cell growth rates,
      adhesion, migration, and ultrastructural morphology were examined. Human
      keratinocytes and fibroblasts attached to all films. Furthermore, small-pore (3-5
      microm) films showed the highest levels of cell adhesion and survival and
      prevented migration into the pores and opposing film surface. Keratinocyte
      migration over small-pore film surface was inhibited. Keratinocytes optimally
      attached to 3-microm-pore films due to a combination of greater pore numbers
      (porosity), a greater circumference of the pore edge per unit surface area, and
      greater frequency of flat surface areas for attachment, allowing better cell
      substrate and cell-cell attachment and growth. The 3-microm pore size allowed
      cell-cell communication, together with diffusion of soluble nutrients and factors
      from the culture medium or wound substrate. These characteristics are considered
      important in developing grafts for use in the treatment of human skin wounds.

PMID- 17228995
TI  - Large-scale genome-wide linkage analysis for loci linked to BMD at different
      skeletal sites in extreme selected sibships.
AB  - Few genome-wide linkage studies of osteoporosis have been conducted in the Asian
      population. We performed a genome-wide scan involving 3093 adult siblings with at
      least one sib-pair extremely concordant or discordant for hip BMD. Our results
      indicated four genome-wide significant QTLs for BMD. In comparison with 12
      previous reported linkage studies, we reveal novel linkage regions that have
      reaching global significance. INTRODUCTION: The genetic basis for osteoporosis
      has been firmly established, but efforts to identify genes associated with this
      complex trait have been incomplete, especially in Asian populations. The purpose
      of this study was to identify quantitative trait loci (QTLs) for BMD in a Chinese
      population. MATERIALS AND METHODS: We performed a genome-wide scan involving 3093
      siblings 25-64 years of age from 941 families, with at least one sib-pair extreme
      concordant or discordant for total hip BMD from a large community-based cohort (n
      = 23,327) in Anhui, China. Linkage analysis was performed on BMD residuals
      adjusted for age, height, weight, occupation, cigarette smoking, physical
      activity, and alcohol consumption using the revised Haseman-Elston regression
      based linkage model. RESULTS: Our results revealed significant QTLs on chromosome
      7p21.2 for femoral neck BMD (LOD = 3.68) and on chromosome 2q24.3 for total hip
      BMD (LOD = 3.65). Suggestive linkage regions were found to overlap among
      different skeletal sites on chromosomes 2q, 7p, and 16q. Sex-specific linkage
      analysis further revealed a significant QTL for lumbar spine BMD on chromosome
      13q21.1 (LOD = 3.62) in women only. When performing multivariate linkage analysis
      by combining BMDs at four skeletal sites (i.e., whole body, total hip, femoral
      neck, and lumbar spine BMD), an additional significant QTL was found at
      chromosome 5q21.2 (LOD = 4.56). None of these significant QTLs found in our study
      overlapped with major QTLs reported by other studies. CONCLUSIONS: This study
      reveals four novel QTLs in a Chinese population and suggests that BMD at
      different skeletal sites may also share common genetic determinants.

PMID- 17228997
TI  - Surgery for fibrous dysplasia.

PMID- 17228998
TI  - Medical therapy of children with fibrous dysplasia.

PMID- 17228999
TI  - Medical therapy in adults with fibrous dysplasia of bone.
AB  - In open studies, bisphosphonate therapy (pamidronate, alendronate) reduced bone
      pain associated with fibrous dysplasia of bone and was associated to some
      radiological improvement. Calcium, vitamin D, and phosphorus supplements may be
      useful in patients with deficiency. We are awaiting results from controlled
      trials testing bisphosphonates. INTRODUCTION: Fibrous dysplasia of bone (FD), a
      rare disease caused by osteoblastic lineage differentiation defects, is
      associated with bone pain, fracture, and bone deformity, but few therapeutic
      options are available. MATERIALS AND METHODS: We reviewed published data on the
      treatment of FD with bisphosphonates (pamidronate, alendronate), calcium, vitamin
      D, and phosphorus. We also present new results on FD therapy with a more potent
      bisphosphonate, zoledronic acid, given intravenously at the dose of 4 mg every 6
      months. RESULTS: Pamidronate therapy, given intravenously every 6 months at a
      dose of 180 mg in adults, relieved bone pain, decreased bone resorption, and
      improved the radiological aspect (filling of lytic lesions and/or thickening of
      cortices) in approximately 50% of patients. BMD in affected sites was also
      significantly increased after pamidronate treatment. Those results have been
      obtained only in open studies, without controls, by several research groups. In a
      series of nine patients on long-term pamidronate treatment, but resisting to this
      medication and switched to intravenous zoledronic acid, no substantial
      improvement was observed. There is some biological rationale supporting the use
      of calcium and vitamin D in patients with deficiency to improve FD lesions by
      limiting secondary hyperparathyroidism. Phosphorus supplementation may prevent
      mineralization defects in those patients who have both FD and renal phosphate
      wasting. However, we are lacking clinical evidence for the efficacy of such
      supplements. CONCLUSIONS: Bisphosphonate treatment reduces increased osteoclastic
      activity in FD and probably improves bone pain, but their use should be better
      studied in randomized controlled trials.

PMID- 17228994
TI  - Meta-analysis of genome-wide scans provides evidence for sex- and site-specific
      regulation of bone mass.
AB  - Several genome-wide scans have been performed to detect loci that regulate BMD,
      but these have yielded inconsistent results, with limited replication of linkage
      peaks in different studies. In an effort to improve statistical power for
      detection of these loci, we performed a meta-analysis of genome-wide scans in
      which spine or hip BMD were studied. Evidence was gained to suggest that several
      chromosomal loci regulate BMD in a site-specific and sex-specific manner.
      INTRODUCTION: BMD is a heritable trait and an important predictor of osteoporotic
      fracture risk. Several genome-wide scans have been performed in an attempt to
      detect loci that regulate BMD, but there has been limited replication of linkage
      peaks between studies. In an attempt to resolve these inconsistencies, we
      conducted a collaborative meta-analysis of genome-wide linkage scans in which
      femoral neck BMD (FN-BMD) or lumbar spine BMD (LS-BMD) had been studied.
      MATERIALS AND METHODS: Data were accumulated from nine genome-wide scans
      involving 11,842 subjects. Data were analyzed separately for LS-BMD and FN-BMD
      and by sex. For each study, genomic bins of 30 cM were defined and ranked
      according to the maximum LOD score they contained. While various densitometers
      were used in different studies, the ranking approach that we used means that the
      results are not confounded by the fact that different measurement devices were
      used. Significance for high average rank and heterogeneity was obtained through
      Monte Carlo testing. RESULTS: For LS-BMD, the quantitative trait locus (QTL) with
      greatest significance was on chromosome 1p13.3-q23.3 (p = 0.004), but this
      exhibited high heterogeneity and the effect was specific for women. Other
      significant LS-BMD QTLs were on chromosomes 12q24.31-qter, 3p25.3-p22.1, 11p12
      q13.3, and 1q32-q42.3, including one on 18p11-q12.3 that had not been detected by
      individual studies. For FN-BMD, the strongest QTL was on chromosome 9q31.1-q33.3
      (p = 0.002). Other significant QTLs were identified on chromosomes 17p12-q21.33,
      14q13.1-q24.1, 9q21.32-q31.1, and 5q14.3-q23.2. There was no correlation in
      average ranks of bins between men and women and the loci that regulated BMD in
      men and women and at different sites were largely distinct. CONCLUSIONS: This
      large-scale meta-analysis provided evidence for replication of several QTLs
      identified in previous studies and also identified a QTL on chromosome 18p11
      q12.3, which had not been detected by individual studies. However, despite the
      large sample size, none of the individual loci identified reached genome-wide
      significance.

PMID- 17229000
TI  - G(s)alpha mutations in fibrous dysplasia and McCune-Albright syndrome.
AB  - Fibrous dysplasia (FD) is a focal bone lesion composed of immature mesenchymal
      osteoblastic precursor cells. Some FD patients also have hyperpigmented skin
      lesions (cafe-au-lait spots), gonadotropin-independent sexual precocity, and/or
      other endocrine and nonendocrine manifestations (McCune-Albright syndrome [MAS]).
      MAS results from somatic mutations occurring during early development, resulting
      in a widespread mosaic of normal and mutant-bearing cells, which predicts that
      the clinical presentation of each patient is determined by the extent and
      distribution of abnormal cells. These mutations encode constitutively active
      forms of G(s)alpha, the ubiquitously expressed G protein alpha-subunit that
      couples hormone receptors to intracellular cAMP generation. These mutations lead
      to substitution of amino acid residues that are critical for the intrinsic GTPase
      activity that is normally required to deactivate the G protein. This leads to
      prolonged activation of G(s)alpha and its downstream effectors even with minimal
      receptor activation. This explains why MAS patients have stimulation of multiple
      peripheral endocrine glands in the absence of circulating stimulatory pituitary
      hormones and increased skin pigment, which is normally induced by melanocyte
      stimulating hormone through G(s)alpha/cAMP. Similar mutations are also present in
      40% of pituitary tumors in acromegaly patients and less commonly in other
      endocrine tumors. FD results from increased cAMP in bone marrow stromal cells,
      leading to increased proliferation and abnormal differentiation. Parental origin
      of the mutated allele may also affect the clinical presentation, because
      G(s)alpha is imprinted and expressed only from the maternal allele in some
      tissues (e.g., pituitary somatotrophs).

PMID- 17229001
TI  - Fibrous dysplasia as a stem cell disease.
AB  - At a time when significant attention is devoted worldwide to stem cells as a
      potential tool for curing incurable diseases, fibrous dysplasia of bone (FD)
      provides a paradigm for stem cell diseases. Consideration of the time and
      mechanism of the causative mutations and of nature of the pluripotent cells that
      mutate in early embryonic development indicates that, as a disease of the entire
      organism, FD can be seen as a disease of pluripotent embryonic cells. As a
      disease of bone as an organ, in turn, FD can be seen as a disease of postnatal
      skeletal stem cells, which give rise to dysfunctional osteoblasts. Recognizing FD
      as a stem cell disease provides a novel conceptual angle and a way to generate
      appropriate models of the disease, which will continue to provide further insight
      into its natural history and pathogenesis. In addition, skeletal stem cells may
      represent a tool for innovative treatments. These can be conceived as directed to
      alter the in vivo behavior of mutated stem cells, to replace mutated cells
      through local transplantation, or to correct the genetic defect in the stem cells
      themselves. In vitro and in vivo models are currently being generated that will
      permit exploration of these avenues in depth.

PMID- 17229002
TI  - Paget's disease of bone in Italy.
AB  - Epidemiological studies of Paget's disease of bone (PDB) suggest a pronounced
      geographical variation in the prevalence of the disease and a decrease in
      prevalence and clinical severity over time. To analyze epidemiological and
      clinical features of PDB in Italy, we recently established a registry of Italian
      PDB cases and performed radiological, biochemical, and bone scan surveys in the
      towns of Siena and Turin. The overall prevalence of PDB in Italy varied between
      0.7% and 2.4%. Prevalence rates increased with age and were higher in men than in
      women. We observed clinically confirmed familial aggregation in 15-26% of cases.
      Pedigree analysis indicated an autosomal dominant pattern of inheritance with
      variable penetrance. SQSTM1 gene analysis in two Italian studies revealed the
      presence of at least three different mutations accounting for both familial and
      sporadic cases. Interestingly, no decrease in the prevalence of PDB over time was
      observed, the opposite of what is described in populations of British descent.
      However, clinical severity of PDB cases included in the Registry in 2002-2004
      seemed reduced with respect to that of PDB patients from the previous
      epidemiological studies, including a 1950-1956 Italian study. Of interest, a
      consistent association between PDB and animal-related factors and a significantly
      higher prevalence of the disease in rural than in urban districts were observed.
      These findings are in keeping with an important role of the environment in the
      pathogenesis of PDB, perhaps facilitating the expression of the disease in
      genetically susceptible subjects. Finally, there was also preliminary evidence
      indicating regional clustering of PDB in Italy, with a concentration of cases in
      rural districts of Campania and Tuscany. These districts may represent high
      prevalence areas of PDB in Italy, similar to what has been observed in other
      countries. Extrapolation estimates suggest that approximately 150,000-300,000
      subjects may be affected with PDB in our country. These results confirm PDB to be
      the most common bone remodeling disorder in elderly people in Italy, excluding
      osteoporosis.

PMID- 17229003
TI  - Biochemical assessment of Paget's disease of bone.
AB  - Biochemical measurements of bone turnover provide an objective assessment of
      disease activity and the response to treatment. Alkaline phosphatase is the best
      characterized of the bone turnover markers and reflects the extent and activity
      of Paget's disease. However, in addition to bone-specific alkaline phosphatase
      (Bone ALP), there is also osteocalcin (OC) and procollagen type 1 N-terminal
      propeptide (P1NP) as formation markers. A variety of telopeptides (C-terminal
      telopeptide of type I collagen, [CTX], N-telopeptide of type I collagen [NTX]) or
      cross-link breakdown products of type 1 collagen can be used to assess bone
      resorption. Total alkaline phosphatase (Total ALP), Bone ALP, and P1NP all
      perform similarly in diagnosis and in evaluating the response to treatment, but
      the general availability, low interassay variation, and inexpensiveness of Total
      ALP makes it the best test for routine use. Measurement of the biological
      variability of the different markers in stable, untreated Paget's disease
      indicates how great a change (critical difference) is needed to define a true
      alteration in disease activity. Bone ALP, P1NP, and NTX show the highest therapy
      induced change/critical difference ratio during antiresorptive treatment. Some of
      the resorption markers show more complex changes in response to treatment.
      Pyridinoline (PYD) or deoxypyridinoline (DPD) cross-links of type 1 collagen are
      excreted in urine either as free or as peptide bound moieties, but it is the
      latter which decrease by the greatest amount in response to bisphosphonate
      therapy. Newly formed type 1 collagen contains an aspartyl-glycine motif
      (alphaCTX), which undergoes spontaneous isoaspartyl formation to betaCTX as the
      bone ages. In untreated Paget's disease, the alphaCTX is raised proportionately
      more (16-fold) than betaCTX (3-fold) and decreases in response to bisphosphonate
      therapy to a greater extent than betaCTX (measured in the sCTX assay). As
      bisphosphonates have become more potent, the aim of treatment has shifted toward
      the achievement of a rate of bone turnover in the lower part of the reference
      range. This is important because the duration of remission of disease activity is
      strongly determined by the post treatment nadir bone turnover.

PMID- 17229004
TI  - Imaging of Paget's disease and fibrous dysplasia of bone.

PMID- 17229005
TI  - Update on the epidemiology of Paget's disease of bone.
AB  - Paget's disease of bone (PDB) is characterized by rapid bone remodeling and the
      formation of bone that is structurally abnormal. Recent studies have confirmed
      that both genetic and environmental factors are important in its etiology.
      Epidemiological studies in Europe and North America have revealed that PDB shows
      an increasing frequency of occurrence with age and is more prevalent among men
      than women. There is marked geographic variation in the prevalence of PDB
      throughout western nations, with the highest rates reported during the 1970s in
      Britain. Recent studies of the secular trends in PDB suggest declining rates in
      both prevalence and severity at diagnosis. Thus, the overall age/sex standardized
      prevalence rate in Britain during the period 1993-1995 was found to be 2.5% among
      men and 1.6% among women > or = 55 years of age. Prevalence rates had fallen by
      approximately 50% in several of the centers studied, suggesting an environmental
      contribution to the etiology of this disorder. Similar findings have been
      reported from other European countries and New Zealand. Recent study of the
      incidence and clinical manifestations of PDB have emerged from large cohort
      studies in primary care record linkage resources, such as the General Practice
      Research Database. Over the period 1988-1999, the incidence rate of clinically
      diagnosed PDB was found to be 5 per 10,000 person-years among men and 3 per
      10,000 person-years among women 75 years of age. The disorder was associated with
      an increased risk of back pain (RR, 2.1; 95% CI, 1.9-2.3); osteoarthritis (RR,
      1.7; 95% CI, 1.5-1.9); and fracture (RR, 1.2; 95% CI, 1.0-1.5). Using life table
      methodology, the estimated proportion of patients dying within 5 years of follow
      up was 32.7% among the cohort with PDB compared with 28.0% among control patients
      (p < 0.05).

PMID- 17229006
TI  - Contribution of genetic factors to the pathogenesis of Paget's disease of bone
      and related disorders.
AB  - Paget's disease of bone (PDB) is a common condition with a strong genetic
      component that is characterized by focal increases in bone turnover, leading to
      bone deformity, pathological fractures, and various other complications. Several
      rare disorders have also been described that show phenotypic overlap with PDB.
      Genome-wide searches have identified several susceptibility loci for PDB and PDB
      like disorders, and mutations that cause these disorders have now been identified
      in four genes, all of which are involved in the RANK-NF-kappaB signaling pathway.
      Mutations in SQSTM1, which encodes an important scaffold protein in this pathway,
      have been found to be a common cause of classical PDB. Thus far, all disease
      causing mutations in SQSTM1 affect the ubiquitin-associated (UBA) domain of the
      gene product and cause loss of ubiquitin binding. The rare PDB-like disorders of
      familial expansile osteolysis, early-onset familial PDB, and expansile skeletal
      hyperphosphatasia are caused by duplication mutations in exon 1 of the TNFRSF11A
      gene, which encodes the RANK receptor. This gene does not seem to be involved in
      the pathogenesis of classical PDB. Inactivating mutations in the TNFRSF11B gene,
      which encodes osteoprotegerin, cause juvenile PDB, and TNFRSF11B polymorphisms
      seem to increase the risk of classical PDB. The rare syndrome of hereditary
      inclusion body myopathy, PDB, and frontotemporal dementia (IBMPFD) is caused by
      mutations in the VCP gene, which is involved in regulating I-kappaB degradation
      by the proteasome. The disease-causing mutations in VCP cluster in and around a
      domain involved in ubiquitin binding. Whereas SQSTM1 has emerged as an important
      gene for classical PDB, most kindreds with familial PDB do not carry SQSTM1
      mutations, indicating that additional genes for PDB remain to be discovered. In
      light of the molecular defects that have been identified thus far, it seems
      likely that these genes will also be involved in the RANK-NF-kappaB signaling
      pathway or its interactions with the ubiquitin-proteasome system.

PMID- 17229007
TI  - Sequestosome 1: mutation frequencies, haplotypes, and phenotypes in familial
      Paget's disease of bone.
AB  - Mutations of the SQSTM1/p62 gene are commonly observed in PDB. Screening an
      updated sample from Quebec and using previously published data from other
      populations, we compared frequency estimates for SQSTM1/p62 mutations and
      haplotype distribution. The P392L mutation was the most prevalent, embedded in
      two different haplotypes, possibly shared by other populations. We also examined
      the phenotype and penetrance of P392L. INTRODUCTION: There is accumulating
      evidence that supports a contribution of genetic factors in the etiology of
      Paget's disease of bone (PDB), and several genetic loci have been suggested for
      the disorder. The sequestosome1/p62 (SQSTM1/p62) gene was the first gene
      identified to have a role in PDB, with 14 mutations reported to date. MATERIAL
      AND METHODS: To evaluate the importance of the SQSTM1/p62 mutations in PDB, we
      recruited, sequenced, and genotyped a total of 123 carriers from 20 families in
      addition to 214 unrelated PDB patients. We compared the frequency of SQSTM1/p62
      mutations in familial and unrelated cases among different populations. Finally,
      we examined the phenotypic expression and penetrance of the P392L mutation in the
      Quebecois families. RESULTS AND CONCLUSIONS: The 14 mutations reported in
      SQSTM1/p62 all affect the ubiquitin-associated domain of the protein. The P392L
      mutation is the most commonly observed mutation in PDB patients and was
      consistently found in unrelated and familial PDB cases in the populations tested.
      Analysis of adjacent polymorphisms suggests that P392L is associated with two
      different haplotypes in the Quebecois patients, similar to what has been observed
      in European populations. In Quebec, both haplotypes had similar frequencies in
      unrelated P392L carriers, whereas one haplotype was predominant in the other
      populations studied. These data suggest that these two haplotypes, possibly
      introduced by European founders in the Quebecois population, were equally
      distributed in the succeeding generations. Finally, the P392L mutation is
      transmitted as an autosomal dominant trait in the Quebecois families, with a high
      but incomplete penetrance peaking after age 60. The large phenotypic variability
      and similarity between unrelated and familial cases, respectively, remain
      unexplained and require further research.

PMID- 17229008
TI  - Clinical and cellular phenotypes associated with sequestosome 1 (SQSTM1)
      mutations.
AB  - Familial Paget's disease of bone has been shown to be associated with mutations
      in the ubiquitin-associated (UBA) domain of the sequestosome 1 (SQSTM1) gene. We
      have clinical findings on five families with diverse racial and ethnic
      backgrounds who all harbor SQSTM1 UBA domain mutations (P387L, P392L, D391fsX394,
      P392fsX394). Intrafamilial expressivity was highly variable. The probands in two
      of the families had early-onset disease involving a large number of bones and
      highly elevated prediagnostic levels of serum alkaline phosphatase. Affected
      siblings in these same families had limited bone involvement and were only
      diagnosed by technetium-99m methylene diphosphonate (MDP) bone scans.
      Furthermore, there was at least one subject in each family with no evidence of
      Paget's disease, although they carried one mutated copy of the SQSTM1 gene. A
      total of 18 such individuals were identified across the five kindreds. Thus, the
      gene seems to have highly variable expressivity, as well as incomplete
      penetrance, supporting the role of this gene as a predisposition gene for
      familial Paget's disease of the bone. Molecular studies of the SQSTM1 protein
      showed different cellular aggregation phenotypes depending on the nature of the
      mutation. In general, the point mutations formed larger cytoplasmic aggregates
      than the wildtype or truncation mutations. This aggregation phenotype was not
      altered on removal of the N-terminal PB1 dimerization domain, implying that
      aggregate formation is not wholly mediated by interaction through the PB1 domain.
      Although there was a genotype/phenotype correlation on the cellular level, this
      was not apparent on the clinical level. This supports the argument that other
      nongenetic factors play an important role in the pathogenesis of the disease.

PMID- 17229009
TI  - Ultrastructure of bone cells in Paget's disease of bone.

PMID- 17229010
TI  - Osteosarcoma in Paget's disease of bone.
AB  - Paget's disease of bone (PDB) is a focal disorder of bone metabolism first
      described by Sir James Paget in 1876. It is presumed benign in nature and
      mediated by abnormal osteoclast function. The incidence of osteosarcomas
      complicating PDB is estimated at <1%. These cancers occur mostly in persons with
      long-standing, polyostotic disease and affect patients in their seventh decade or
      when osteosarcoma is remarkably rare in the general population. Epidemiological
      studies suggest that this late peak of osteosarcomas is absent in regions where
      Paget's is infrequently reported. Whereas PDB has a predilection for the axial
      skeleton, skull, femurs, and tibias, pagetic osteosarcoma tend to spare the
      spine, and are reported more commonly in the pelvis, femur, humerus, and skull. A
      molecular basis for the association of osteosarcoma with Paget's disease is
      unclear. These osteosarcomas are osteogenic in origin, consistently arise in
      sites of pagetic bone, and may present as metachronous, multifocal lesions. On
      histopathology, the lesions are usually osteoblastic, and the tumor phenotype is
      sometimes characterized as an exaggerated, chaotic form of the accelerated bone
      remodeling that characterizes PDB. New insights from the biology of adolescent
      osteosarcomas, VCP and SQSTM1 mutations now defined in patients with Paget's
      disease, and emerging evidence that stromal lesions are present in patients with
      Paget's disease are changing the way we think about the pathogenesis of PDB and
      the rare complication of pagetic osteosarcomas.

PMID- 17229011
TI  - Nonmalignant complications of Paget's disease.
AB  - Paget's disease of bone is a focal or multifocal disorder characterized by
      intense disorderly remodeling activity at sites of involvement, producing
      dramatic alterations of local bone architecture. These functional and structural
      alterations, interacting with the specific characteristics of the site of
      involvement, account for most of the complications of the disease. This
      presentation will focus on selected nonneoplastic complications of particular
      current interest.

PMID- 17229012
TI  - What is the relationship between Paget's disease of bone and hyperparathyroidism?

PMID- 17229013
TI  - Surgical management of Paget's disease of bone.
AB  - Paget's disease is a chronic nonmetabolic bone disorder that is characterized by
      increased bone resorption, bone formation, and remodeling. This unbalanced
      process may lead to osseous deformities, structural weakness, and altered joint
      biomechanics, all of which can make surgical reconstruction difficult. Although
      few patients with Paget's disease ever need surgical treatment, successful
      surgical management of orthopedic manifestations of the disease has improved the
      quality of life for these patients. Surgical options include corrective osteotomy
      for long bone deformity, fracture fixation, joint arthroplasty, spinal
      decompression, and tumor resection. Patients are at increased risk for surgical
      complications such as blood loss and heterotopic bone formation. Issues relating
      to the surgical management of patients with Paget's disease such as appropriate
      preoperative diagnosis, technical challenges of surgery, and strategies to
      improve the long-term outcome of surgical intervention are discussed.

PMID- 17229014
TI  - Zoledronate: efficacy and safety.

PMID- 17229015
TI  - Acquired resistance to bisphosphonates in Paget's disease of bone.

PMID- 17229016
TI  - Is the prevalence of Paget's disease of bone decreasing?
AB  - Secular trends in the severity and prevalence of Paget's disease over a 30-year
      period are described. Paget's disease has become less prevalent and patients are
      presenting later, with less severe disease than previously. These data suggest
      that environmental factors are important in the etiology of Paget's disease.
      INTRODUCTION: Data from several countries support the view that there are
      important secular trends in the prevalence and severity of Paget's disease. In
      this paper, recent trends in the epidemiology of Paget's disease are described.
      MATERIALS AND METHODS: A database of all newly referred patients (n = 1487) with
      Paget's disease (1973-2002 inclusive, 30 years) was examined. Of these subjects,
      56% had scintiscans. Plasma total alkaline phosphatase (total ALP) activity and
      disease extent on scintiscan were used as indices of severity. A radiographic
      prevalence survey of 1019 subjects of European origin >55 years of age in Dunedin
      was undertaken- approximately 20 years after an earlier survey had shown New
      Zealand to be a high prevalence area. RESULTS: The number of new referrals with
      Paget's disease declined sharply from 1994 onward, to one half the rate seen 20
      years earlier, whereas the mean age at presentation increased by 4 years per
      decade (p < 0.0001). Total ALP at diagnosis, disease extent on scintiscan, and
      the number of bones involved were all negatively correlated with both date of
      birth (p < 0.0001) and year of presentation (p < 0.0001), indicating that more
      recently born and presenting subjects had substantially less severe bone disease.
      The radiographic survey showed that the current prevalence was only approximately
      50% of that in the 1983 survey (p = 0.012). CONCLUSIONS: Although there are a
      number of potential biases, these data are consistent with a continued secular
      trend to presentation in older subjects with less extensive skeletal involvement
      and a declining prevalence of Paget's disease.

PMID- 17229017
TI  - Guidelines for the diagnosis and management of Paget's disease: a UK perspective.

PMID- 17229018
TI  - Medical management of Paget's disease of bone: indications for treatment and
      review of current therapies.
AB  - Treatment with a potent bisphosphonate is indicated in patients with Paget's
      disease who have symptoms likely to respond to reduced bone turnover at pagetic
      sites. In asymptomatic patients with active disease at sites susceptible to local
      progression and late complications, treatment is also recommended. Biochemical
      remission is achievable in a majority of patients with pamidronate, alendronate,
      risedronate, or zoledronic acid. Indications for medical treatment of active
      Paget's disease of bone include symptoms referable to sites of the disease such
      as bone pain, joint pain, and neurological complications; elective surgery at an
      active pagetic site to reduce intraoperative blood loss from highly vascular
      bone; management of rare instances of immobilization hypercalcemia with
      polyostotic disease; and presence of disease activity in asymptomatic patients at
      sites at risk for future complications to limit progression and possibly lower
      that risk. The treatment of choice is a potent nitrogen-containing
      bisphosphonate, including oral alendronate or risedronate or intravenous
      pamidronate or zoledronic acid. Etidronate and tiludronate are less potent and
      are second-line choices. Recent data with zoledronic acid indicate that a single
      infusion of 5 mg is associated with normalization of serum alkaline phosphatase
      in 89% of patients and a prolonged biochemical remission, making it the most
      effective therapy available to date. Side effect profiles with alendronate and
      risedronate include esophageal irritation in a minority of patients. Intravenous
      pamidronate and zoledronic acid may induce an acute phase reaction with fever and
      flu-like symptoms with the first dose, primarily in patients who are treatment
      naive to nitrogen-containing bisphosphonates. Calcium and vitamin D repletion are
      mandatory with these potent anti-osteoclast therapies to avoid hypocalcemia.
      Acquired resistance to etidronate and pamidronate has been reported in some
      patients, leading to lesser reductions in bone turnover and shorter periods of
      remission, but substitution with a different bisphosphonate provides a more
      robust response. It is not known whether resistance to other bisphosphonates in
      Paget's disease occurs.

PMID- 17229019
TI  - Spectrum and natural history of fibrous dysplasia of bone.

PMID- 17229020
TI  - Experimental models of Paget's disease.
AB  - We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice
      developed abnormal OCLs and bone lesions similar to those found in Paget's
      patients. These results show that persistent expression of MVNP in OCLs can
      induce pagetic-like bone lesions in vivo. INTRODUCTION: Paget's disease (PD) is
      one of the most exaggerated examples of abnormal bone remodeling, with increased
      bone resorption and excessive new bone formation. However, its etiology is
      unclear. A viral etiology for PD has been suggested based on the presence of
      paramyxoviral-like nuclear inclusions, detection of measles virus nucleocapsid
      (MVNP) mRNA or protein in osteoclasts (OCLs) from PD lesions, and in vitro
      studies showing that transfection of normal OCL precursors with the MVNP gene
      results in formation of OCLs that express a pagetic phenotype (increased numbers
      of OCLs; increased responsivity to 1,25(OH)(2)D(3), RANKL, and TNF-alpha;
      increased expression of the TAF(II)-17 gene, and increased bone resorption
      capacity). MATERIALS AND METHODS: We targeted MVNP to cells in the OCL lineage in
      transgenic mice using the TRACP promoter. RESULTS: Histomorphometric analysis
      showed that there was a 64% increase in OCL perimeter (p = 6.0002) and 37%
      increase in osteoblast (OBL) perimeter in MVNP mice. In a mouse that was 14
      months of age, there was a 225% increase in OBL perimeter and 149% in OBL
      perimeter. This was accompanied by increased cancellous bone volume (83%) and
      trabecular width (47%) and number (25%), with a marked increase in the amount of
      woven bone. In contrast, cancellous bone volume decreased between 3 and 12 months
      in wildtype (WT) mice, whereas cancellous bone volume in MVNP mice increased over
      the same time period. Ex vivo studies showed that the numbers of OCLs formed in
      marrow cultures from MVNP mice were increased, and the OCLs were hyper-responsive
      to 1,25(OH)(2)D(3) and had an increased bone resorbing capacity compared with WT
      cultures. CONCLUSION: These results show that expression of MVNP in OCL in vivo
      results in a bone phenotype that is characteristic of PD.

PMID- 17229021
TI  - Lessons from the NHS National Programme for IT.

PMID- 17229022
TI  - Promoting community awareness of the link between illicit drugs and mental
      disorders.

PMID- 17229023
TI  - New Year's resolution: let's get rid of excessive food prices in remote
      Australia.

PMID- 17229024
TI  - The increasing cost of the basic foods required to promote health in Queensland.
AB  - OBJECTIVE: To assess changes in the cost and availability of a standard basket of
      healthy food items (the Healthy Food Access Basket [HFAB]) in Queensland over
      time. DESIGN AND PARTICIPANTS: A series of four cross-sectional surveys (in 1998,
      2000, 2001 and 2004) describing the cost and availability of foods in the HFAB
      over time. In the latest survey, 97 Queensland food stores across the five
      Australian Bureau of Statistics remoteness categories were compared. MAIN OUTCOME
      MEASURES: Cost comparisons for HFAB items by remoteness category for the 97
      stores surveyed in 2004; changes in cost and availability of foods in the 81
      stores surveyed since 2000; comparisons of food prices in the 56 stores surveyed
      in 1998, 2000, 2001 and 2004. RESULTS: In 2004, the Queensland mean cost of the
      HFAB was $395.28 a fortnight. The cost of the HFAB was 29.6% ($113.89) higher in
      "very remote" areas than in "major cities" (P < 0.001). Between 2001 and 2004,
      the Queensland mean cost of the HFAB increased by 14.0% ($48.45), while in very
      remote areas the cost increased by 18.0% ($76.93) (P < 0.001). Since 2000, the
      annualised per cent increase in cost of the HFAB has been higher than the
      increase in Consumer Price Index for food in Brisbane. The cost of healthy foods
      has risen more than the cost of some less nutritious foods, so that the latter
      are now relatively more affordable. CONCLUSIONS: Consumers, particularly those in
      very remote locations, need to pay substantially more for basic healthy foods
      than they did a few years ago. Higher prices are likely to be a barrier to good
      health among people of low socioeconomic status and other vulnerable groups.
      Interventions to make basic healthy food affordable and accessible to all would
      help reduce the high burden of chronic disease.

PMID- 17229025
TI  - Nutrition-related disorders in Indigenous Australians: how things have changed.
AB  - Awareness of a serious Indigenous health problem in Australia did not emerge
      until the 1960s and 1970s. Much attention was focused at the time on poor
      pregnancy outcomes, high infant and young child mortality rates, and childhood
      malnutrition and impaired growth, often associated with high infectious disease
      burdens. Although that situation has improved somewhat, Indigenous infant and
      child health is still poor compared with that of other Australian children. Over
      recent decades, there has been a rapid rise among Indigenous people of nutrition
      related "lifestyle" disorders such as obesity, cardiovascular disease, type 2
      diabetes mellitus and chronic renal disease and their complications. This
      epidemic of disabling and often fatal chronic diseases in Indigenous Australians
      is also occurring in disadvantaged groups in many other countries. Control of
      this potentially disastrous epidemic must become a much higher priority in
      Indigenous health programs. Governments must commit to this task in cooperation
      and collaboration with Indigenous organisations and communities.

PMID- 17229026
TI  - Children's television sub-standards: a call for significant amendments.

PMID- 17229027
TI  - Traffic-light food labels.

PMID- 17229028
TI  - Obesity, law and personal responsibility.

PMID- 17229029
TI  - High risk-factor level and low risk-factor knowledge in patients not accessing
      cardiac rehabilitation after acute coronary syndrome.
AB  - OBJECTIVE: To document the risk-factor profile and risk-factor knowledge of
      patients with an acute coronary syndrome (ACS) not attending standard cardiac
      rehabilitation. DESIGN AND SETTING: Cross-sectional comparison in a tertiary
      hospital. PARTICIPANTS: Patients admitted to hospital with an ACS, residing
      within 20 km of the hospital, and without severe comorbidity who did not access
      cardiac rehabilitation (NCR) were compared with a group about to commence
      standard cardiac rehabilitation (SCR). MAIN OUTCOME MEASURES: Risk-factor
      profile, knowledge of risk factors via face-to-face assessment, quality of life.
      RESULTS: Of the 446 patients eligible for cardiac rehabilitation, 208 attended
      for assessment (NCR: n = 144; SCR: n = 64). The NCR group had higher mean (+/-
      SEM) low-density lipoprotein (LDL) cholesterol levels (2.6 +/- 0.1 v 2.3 +/- 0.1;
      P = 0.02), and were more likely than the SCR group to have a total cholesterol
      level of > 4.0 mmol/L (78% v 53%; P < 0.001) and an LDL cholesterol level > 2.5
      mmol/L (47% v 25%; P = 0.01). They were more likely than the SCR group to be
      physically inactive (77% v 22%; P < 0.001); obese (46% v 33%; P = 0.04);
      depressed (21% v 5%; P < 0.001); or current smokers (21% v 1%; P < 0.001).
      Compared with the SCR group, the NCR group also had higher risk scores (LIPID
      risk score) (4.5 v 2.1; P < 0.001); lower quality of life (Medical Outcome Short
      Form [SF-36] Health Survey); and significantly poorer knowledge of risk factors.
      Among patients with at least two modifiable cardiac risk factors, the NCR group
      were less likely than the SCR group to be able to state at least one risk factor
      (24% v 38%; P < 0.001). CONCLUSIONS: Patients not participating in cardiac
      rehabilitation after an ACS have more adverse risk profiles and poorer knowledge
      of risk factors compared with those about to commence cardiac rehabilitation.
      Alternate models for secondary prevention are required to improve health outcomes
      in patients not attending cardiac rehabilitation.

PMID- 17229030
TI  - Workforce trends in specialist and GP obstetric practice in Victoria.
AB  - OBJECTIVE: To provide a contemporary picture of the general practitioner and
      specialist obstetric workforce in Victoria. DESIGN, PARTICIPANTS AND SETTING:
      Postal census by questionnaire of all 317 Fellows and 961 Diplomates on the
      Victorian database of the Royal Australian and New Zealand College of
      Obstetricians and Gynaecologists in September 2003. MAIN OUTCOME MEASURES: Sex,
      age and geographical distributions and patterns of retirement from and
      recruitment to the GP and specialist obstetric workforce in Victoria. RESULTS:
      244 Fellows (77.0%) and 652 Diplomates (67.8%) participated. The average age of
      Diplomates was 42 years; only 20% were involved in procedural obstetrics. Of GPs
      practising procedural obstetrics, 56% intended to cease within 7 years. Two
      thirds of specialist obstetricians continued to practise obstetrics. Among those
      ceasing obstetrics, almost half had done so since 2000. Among Fellows ceasing
      obstetric practice, there is a peak in the 50-60-years age group, but cessation
      of obstetric practice occurred across all age groups. CONCLUSION: The proportion
      of GPs involved in procedural obstetrics has fallen markedly over the past
      decade, with half of those ceasing practice in the 40-50-years age group. New GPs
      entering the workforce with the Diploma and overseas doctors are unlikely to meet
      the procedural workforce shortfall. Attracting the large cohort of doctors aged
      40-50 years back to obstetric practice must be a priority. Given the pattern of
      retirements from obstetrics, there will be insufficient numbers of specialists to
      maintain current levels of service. The reasons include non-participation in
      obstetrics by new graduates and international medical graduates, the inadequate
      number of new graduates, and the predominance of women among specialists aged
      under 40 years, whose work output tends to be affected by family commitments.

PMID- 17229031
TI  - Ladders revisited.
AB  - OBJECTIVE: To describe the epidemiology of falls from ladders in a state-wide
      population. DESIGN AND SETTING: Retrospective review of data from the the
      Victorian State Trauma Registry and the Victorian Emergency Minimum Dataset on
      patients presenting to public hospital emergency departments (EDs) with injuries
      due to a fall while climbing a ladder, from 1 July 2001 to 30 June 2005. MAIN
      OUTCOME MEASURES: Overall trends in the incidence of ladder-related ED
      presentations, and in cases of major trauma, trends according to age, and trends
      according to activity at the time of the fall. RESULTS: 4553 patients presented
      to EDs after falls from ladders in Victoria during the study period; 160 patients
      had injuries classified as major trauma. There has been a significant rise in the
      number of presentations to EDs following falls from ladders in Victoria, with a
      marked increase in the number of cases involving patients aged over 50 years and
      those climbing ladders outside of paid working conditions. Deaths occurred
      predominantly in the elderly after falls from heights above 1 metre. CONCLUSIONS:
      Despite knowledge of the dangers of falls from ladders, there has been a
      significant increase in the number of patients presenting to hospitals after
      ladder falls. Middle-aged to elderly patients undertaking unpaid work account for
      this increase. A targeted public health initiative is required to curb this
      trend.

PMID- 17229032
TI  - National guidelines on alcohol use during pregnancy: a dissenting opinion.
AB  - New national guidelines recommend that women who choose to drink alcohol during
      pregnancy "should have less than seven standard drinks" in any week and "no more
      than two standard drinks" on any one day, and that they should never become
      intoxicated. Exposure to alcohol at these recommended levels has been shown to
      affect brain development and certain behaviours in animals. Some longitudinal
      studies in human children have detected detrimental affects from exposure to low
      levels of alcohol. Normal public health standards for exposure to environmental
      toxins should be applied for the unborn baby. We do not know what level of
      alcohol exposure is safe and pregnant women can only be advised to abstain.

PMID- 17229033
TI  - Animal and human bite injuries in Victoria, 1998-2004.
AB  - OBJECTIVE: To describe the epidemiology of mammal (human and non-human) bite
      injuries in Victoria. PARTICIPANTS, DESIGN AND SETTING: Retrospective case series
      of injuries recorded in the Victorian Emergency Minimum Dataset (VEMD) (1998
      2004) and deaths recorded in the National Coroners Information System (1 July
      2000 - 1 June 2006). MAIN OUTCOME MEASURES: Frequency, nature and outcome of
      injury as a function of mammal, victim demographics and season. RESULTS: Of 12
      982 bite injuries identified in the VEMD, dogs, humans, and cats were implicated
      in 79.6%, 8.7%, and 7.2% of cases, respectively. Dog bite injuries were commonly
      sustained to the hands/wrists (31.3%) and face/head (25.4%); cat bites to the
      hands/wrists (67.6%) and arms (16.0%); and human bites to the hands/wrists
      (37.1%), arms (20.5%) and face/head (20.4%). Males comprised 73.7% and 56.3% of
      human and dog bite victims, respectively, while females comprised 64.1% of cat
      bite victims. A third of dog bite victims (33.4%) were children aged 14 years or
      less. Most human bite victims (79.8%) were adults aged 20-49 years, inclusive.
      More injuries were sustained on weekends and during the summer, 55.4% of injuries
      occurred in the home, and 11.6% of patients required hospital admission. Dog
      bites resulted in three deaths. CONCLUSIONS: Mammal bite injuries are common and
      often require inpatient care. Patterns of bite injuries relate to the type of
      mammal involved. These epidemiological data will inform prevention initiatives to
      decrease the incidence of mammal bites.

PMID- 17229034
TI  - Spotted black snake (Pseudechis guttatus) envenoming.
AB  - We report two cases of spotted black snake (Pseudechis guttatus) envenoming. One
      patient experienced localised burning pain around the bite and developed nausea,
      vomiting, diarrhoea, upper abdominal cramping and diaphoresis. He was treated
      with intravenous fluids and antiemetics, but no antivenom, and was discharged 23
      hours after the bite. The second patient developed a severe headache, blurred
      vision and mild nausea, associated with severe pain and swelling of the bitten
      limb that took 4 days to resolve. No antivenom was given and the patient had no
      sequelae. Neither patient developed significant coagulopathy, myolysis or
      neuromuscular paralysis. Bites by this species appear to cause effects similar to
      those of the more common red-bellied black snake (P. porphyriacus).

PMID- 17229035
TI  - Treatment of jellyfish stings.

PMID- 17229036
TI  - A "paneful" perforation.
AB  - Radiographs of a woman presenting with abdominal pain revealed a large foreign
      body within the pelvis. A diagnosis of perforation of the colon was made, and at
      laparotomy an 8.5 cm long glass fragment was removed from the bowel. A laceration
      to the lower back, sustained in a fall onto a glass coffee table, had been
      explored and sutured 20 months earlier. Imaging findings showed the subsequent
      course of the overlooked glass fragment within the pelvis.

PMID- 17229037
TI  - Gone fishing.

PMID- 17229038
TI  - Superior mesenteric artery syndrome with hepatic portal venous gas.

PMID- 17229039
TI  - Editors' review of 2006 and the BJCP prize.

PMID- 17229041
TI  - A cross-sectional study evaluating the relationship between cortisol suppression
      and asthma control in patients with difficult asthma.
AB  - AIM: To examine the relationship between cortisol suppression and asthma symptoms
      in patients with difficult asthma. METHODS: Patients, referred to a specialist
      difficult asthma service and who fulfilled the criteria for difficult asthma,
      were recruited to the study in a sequential, unselected manner. At each clinic
      visit, all patients completed a validated asthma control questionnaire. For
      measuring cortisol suppression, early morning urinary cortisol [corrected for
      creatinine to give urinary cortisol creatinine ratio (UCC ratio)] was used. The
      urine samples were collected and stored at -70 degrees C until ready for
      analysis. Urinary cortisol was extracted (solid-phase extraction) and analysed
      using high-performance liquid chromatography. The Pearson correlation coefficient
      was used for correlation analysis while t-tests were used for between-group
      differences for normally distributed data. If the data were not normally
      distributed, nonparametric statistics were used. A P-value < 0.05 was considered
      statistically significant. RESULTS: During the study period all the patients who
      attended the difficult asthma clinic and fulfilled the criteria for difficult
      asthma (n = 66) agreed to take part in the study. There were moderate to strong
      and significant associations between several measures of asthma control and UCC
      ratio. The correlation coefficient with five indicators of asthma control ranged
      between 0.3 and 0.5 (P < 0.05). CONCLUSIONS: We have demonstrated a relationship
      between cortisol suppression and asthma control in difficult asthmatics on high
      dose steroid therapy. We have proposed a model based on the relationship between
      symptom control and cortisol suppression, whereby both adherence and therapeutic
      adjustments could potentially be made. A properly controlled prospective clinical
      trial should examine the utility of this approach in clinical practice.

PMID- 17229040
TI  - Pharmacokinetics of cysteamine bitartrate following gastrointestinal infusion.
AB  - AIMS: Although cysteamine was first used in the treatment of cystinosis in 1976
      and approved by the FDA as cysteamine bitartrate (Cystagon) in 1994, surprisingly
      little pharmacological data are available for this compound. Cysteamine and its
      related drugs are currently being evaluated for the treatment of Huntington's and
      Parkinson's disease. The aim of te study was to understand the pharmacokinetics
      of cysteamine bitartrate following gastrointestinal infusion. METHOD: Cysteamine
      bitartrate was delivered through a naso-enteric catheter into the stomach (n =
      8), small intestine (n = 8) and caecum (n = 4) of normal subjects. Plasma
      cysteamine concentrations were determined using LC-MS/MS. RESULTS: The rate and
      extent of drug absorption were assessed by comparing AUC(0, infinity), C(max) and
      t(max), among the gastrointestinal infusion sites. Total cysteamine exposure,
      expressed as area under the curve (AUC(0, infinity)) was greatest when the drug
      was infused into the small intestine (4331.3 +/- 1907.6 min x microM) followed by
      stomach (3901.9 +/- 1591.9 min x microM) and caecum (3141.4 +/- 1627.6 min x
      microM). Cysteamine infusion into the small intestine resulted in the most rapid
      rise to maximal plasma concentrations (t(max) = 21 +/- 0.56 min); t(max) was
      delayed to 50 +/- 26 min and 64 +/- 26 min after gastric and caecal infusion,
      respectively. The maximum cysteamine plasma concentration (C(max)) was reached
      after infusion of the drug into the small intestine (51 +/- 21 microM), which was
      higher than plasma C(max) concentrations after gastric (39 +/- 16 microM) and
      caecal infusion (23 +/- 15 microM). CONCLUSIONS: The pharmacokinetic data
      generated help extend our understanding of cysteamine.

PMID- 17229042
TI  - Loxosceles spider venom induces the release of thrombomodulin and endothelial
      protein C receptor: implications for the pathogenesis of intravascular
      coagulation as observed in loxoscelism.
AB  - BACKGROUND: The venom of the spider Loxosceles can cause both local and systemic
      effects including disseminated intravascular coagulation. AIM: The aim of this
      study was to investigate the effects of the venom of Loxosceles intermedia (L.
      intermedia) and the purified Sphingomyelinase D (SMaseD) toxin upon the Protein C
      (PC) natural anticoagulant pathway. RESULTS: Both the venom and e purified SMaseD
      reduced the cell surface expression of thrombomodulin (TM) and Endothelial PC
      Receptor on endothelial cells in culture. The reduction of cell surface
      expression was caused by cleavage from the cell surface mediated by activation of
      an endogenous metalloproteinase. Reduction of TM and Endothelial PC Receptor on
      the surface of these cells resulted in an impaired ability of the cells to assist
      in the thrombin-induced activation of PC. CONCLUSION: This novel observation
      gives further insight into the mechanisms of the pathology induced by venom from
      Loxosceles spiders and may aid the development of a suitable therapy.

PMID- 17229043
TI  - Venous thrombotic complications in adults undergoing induction treatment for
      acute lymphoblastic leukemia: results from a meta-analysis.

PMID- 17229044
TI  - Spatiotemporal control of vascular endothelial growth factor delivery from
      injectable hydrogels enhances angiogenesis.
AB  - Therapeutic angiogenesis with vascular endothelial growth factor (VEGF) delivery
      may provide a new approach for the treatment of ischemic diseases, but current
      strategies to deliver VEGF rely on either bolus delivery or systemic
      administration, resulting in limited clinical utility, because of the short half
      life of VEGF in vivo and its resultant low and transient levels at sites of
      ischemia. We hypothesize that an injectable hydrogel system can be utilized to
      provide temporal control and appropriate spatial biodistribution of VEGF in
      ischemic hindlimbs. A sustained local delivery of relatively low amounts of
      bioactive VEGF (3 mug) with this system led to physiologic levels of bioactive
      VEGF in ischemic murine (ApoE(-/-)) hindlimbs for 15 days after injection of the
      gel, as contrasted with complete VEGF deprivation after 72 h with bolus
      injection. The gel delivery system resulted in significantly greater angiogenesis
      in these limbs as compared to bolus (266 vs. 161 blood vessels mm(-2)). Laser
      Doppler perfusion imaging showed return of tissue perfusion to normal levels by
      day 28 with the gel system, whereas normal levels of perfusion were never
      achieved with saline delivery of VEGF or in control mice. The system described in
      this article could represent an attractive new generation of therapeutic delivery
      vehicle for treatment of cardiovascular diseases, as it combines long-term in
      vivo therapeutic benefit (localized bioactive VEGF for 1-2 weeks) with minimally
      invasive delivery.

PMID- 17229045
TI  - Getting to grips with complexity of disease will make genomics useful in arterial
      thrombosis.

PMID- 17229046
TI  - Preanalytical conditions that affect coagulation testing, including hormonal
      status and therapy.
AB  - Preanalytical conditions, be they due to the individual's physiologic state or to
      exogenous factors, can affect coagulation factors, in either a transient or a
      persistent manner, and need to be considered in laboratory testing. These
      conditions include physical and mental stress, diurnal variation, hormone levels
      and posture at the time of blood drawing. While testing of these factors has not
      been exhaustive and some results are conflicting, guidelines for testing
      conditions can be given.

PMID- 17229049
TI  - Fibrinogen and factor VIIc levels: independent risk factors or markers of
      coronary disease risk?

PMID- 17229050
TI  - Detecting antithrombin deficiency may be a difficult task--more than one test is
      necessary.

PMID- 17229051
TI  - A cross-reactive material positive variant of coagulation factor XI (FXIP520L)
      with a catalytic defect.
AB  - Inherited deficiency of the trypsin-like protease factor (F) XI is associated
      with a mild to moderate bleeding diathesis. In most cases, FXI protein is reduced
      in plasma, and examples of dysfunctional circulating FXI variants are rare. We
      characterized the defect in one such variant with a proline to leucine
      substitution at residue 520. FXI Pro520 corresponds to chymotrypsin Pro161, and
      is conserved in most members of the chymotrypsin protease family. Recombinant FXI
      containing this substitution will be referred to as FXI(P161L). k(cat) for
      cleavage of chromogenic substrates and for activation of the natural FXIa
      substrate FIX is approximately 3-fold lower for activated FXI(P161L)
      (FXIa(P161L)) than for wild-type FXIa (FXIa(WT)), consistent with an abnormal
      protease active site. Inhibition of FXIa(P161L) by diisopropyl fluorophosphate is
      2.4-fold slower than for FXIa(WT), suggesting distortion of the protease oxyanion
      hole. Binding to p-aminobenzamidine, a probe for the integrity of the S1
      substrate-binding site, was similar for FXIa(WT) and FXIa(P161L). Rates of
      carbamylation of Ile16 were also similar for FXIa(WT) and FXIa(P161L), indicating
      that the critical salt bridge between Ile16 and Asp194 forms normally during
      protease activation. Cumulatively, the data demonstrate that Pro161 is required
      for normal active site oxyanion hole conformation in FXIa. Examination of the
      FXIa crystal structure and modeling studies indicate that Pro161 forms several
      hydrophobic contacts with adjacent amino acids that stabilize active site
      conformation. Leucine can be incorporated at position 161 in FXIa, but would not
      form the extensive stabilizing network of hydrophobic interactions formed by
      Pro161.

PMID- 17229052
TI  - Characterization of endothelial-like cells derived from human mesenchymal stem
      cells.
AB  - BACKGROUND: Blood-derived endothelial progenitor cells (EPC) have been used to
      treat ischemic disease. However, the number of EPC that can be obtained from
      adult blood is limited. OBJECTIVE: To characterize endothelial-like cells
      obtained from human bone marrow and determine their ability to stimulate new
      blood vessel formation in vivo. METHODS: Mononuclear cells (MNC) were isolated
      from human bone marrow or umbilical cord blood and cultured in endothelial growth
      medium (EGM-2). Mesenchymal stem cells (MSC) were isolated from bone marrow and
      induced to differentiate into endothelial-like cells (MSCE), or adipocytes or
      osteocytes by growth in EGM-2, adipogenic or osteogenic medium. RESULTS: Cells
      obtained by culturing bone marrow MNC in EGM-2 formed cord- or tube-like
      structures when grown on Matrigel(TM) and expressed several endothelial marker
      proteins. However, cell morphology and the profile of endothelial marker protein
      expression were different from those of cord blood-derived EPC (cbEPC). Cells
      with a similar phenotype were obtained by differentiation of MSC into MSCE, which
      was accompanied by an increase of endothelial marker proteins and a diminished
      capacity to differentiate into adipocytes. Subcutaneous implantation of MSCE in
      collagen plugs in non-obese diabetic-severe combined immunodeficient (NOD-SCID)
      mice resulted in formation of functional blood vessels that had incorporated the
      MSCE. CONCLUSIONS: Our results show that MSCE and cbEPC are different cell types.
      The formation of functional blood vessels by MSCE, combined with high yields and
      a reduced capacity to differentiate into other cell types compared with MSC,
      makes these cells potentially useful for autologous therapy of ischemic disease.

PMID- 17229053
TI  - Generation of soluble P- and E-selectins in vivo is dependent on expression of P
      selectin glycoprotein ligand-1.
AB  - BACKGROUND: Factors contributing to the generation of soluble P- and E-selectins
      remain unclear. RESULTS: This work demonstrates that mice lacking P-selectin
      glycoprotein ligand-1 (Psgl-1(-/-)) are deficient in soluble P-selectin (sP-sel),
      which is due to a defective binding interaction between PSGL-1 and P-sel, because
      mice lacking alpha(1,3)-fucosyltransferase-VII are also deficient in sP-sel. Psgl
      1(-/-) mice are also deficient in soluble E-selectin (sE-sel) indicating that
      leukocyte interactions with endothelial cells lead to the generation of sE-sel.
      The generation of sE-sel requires an interaction between PSGL-1 and P-sel, as
      deficiency of sE-sel is observed in both Psgl-1(-/-) and P-sel(-/-) mice. Bone
      marrow transplantation from Psgl-1(-/-) to Psgl-1(+/+) mice leads to deficiency
      of sP-sel and sE-sel in recipient mice, establishing the importance of bone
      marrow-derived PSGL-1 toward the generation of sP-sel and sE-sel. Bone marrow
      transplantation from P-sel(-/-) to P-sel1(+/+) mice does not lead to a
      significant reduction in sP-sel, confirming the importance of the endothelium
      toward the liberation of sP-sel. CONCLUSION: sP-sel and sE-sel reflect an
      interaction between leukocyte PSGL-1 and endothelial P-sel.

PMID- 17229054
TI  - The quality of oral anticoagulant therapy and recurrent venous thrombotic events
      in the Leiden Thrombophilia Study.
AB  - BACKGROUND: The International Normalized Ratio (INR) target range is a relatively
      narrow range in which the efficacy of oral anticoagulant treatment, i.e.
      prevention of extension and recurrence of thrombosis, is balanced with the risk
      of hemorrhagic complications. Over the years, different INR target ranges have
      been implemented for individual indications, depending on their thrombotic
      potential. In most of the studies defining these INR targets, the treatment of
      the patients was aimed at a certain INR range, but in the analysis no account was
      taken of the time that the patients spent within this range in reality. METHODS:
      The Leiden Thrombophilia Study (LETS) is a population-based case-control study on
      risk factors for venous thrombosis, in which many genetic and acquired factors
      have been investigated. Our aim was to investigate the effect of the quality of
      the oral anticoagulant therapy for the initial venous thrombosis and its
      relationship with recurrence of thrombosis. Quality of anticoagulation was
      defined as the time spent at various INR levels during treatment, and we focused
      on the effect of sustained intensities above a certain INR in preventing
      recurrences later on. RESULTS: Two hundred and sixty-six patients with a total
      follow-up of 2495 patient-years were studied. The mean duration of the initial
      anticoagulant therapy was 194.5 days (range 48-4671). During follow-up, 58
      recurrences were diagnosed (cumulative recurrence rate of 21.8% over 9 years).
      The mean INR during initial therapy was 2.90, with 90.3% [95% confidence interval
      (CI) 88.4-92.3%] of the time being spent above an INR of 2.0, and 39.1% (95% CI
      35.5-42.7%) above an INR of 3.0. Patients who spent more time below the target
      range, or who had a shorter duration of anticoagulation, did not experience a
      higher risk of recurrence after the initial period of anticoagulation had passed.
      CONCLUSION: Provided that oral anticoagulant treatment is adequately managed,
      according to international guidelines, recurrent thrombosis cannot be ascribed to
      variation in the primary treatment. Further attempts to reduce the risk of
      recurrence should therefore be aimed at identifying other explanatory factors,
      and subsequently fine-tuning the target ranges.

PMID- 17229055
TI  - Dietary supplement use among anticoagulation clinic patients.

PMID- 17229056
TI  - Preferential localization of recombinant factor VIIa to platelets activated with
      a combination of thrombin and a glycoprotein VI receptor agonist.
AB  - BACKGROUND: Activation of platelets with a combination of collagen and thrombin
      generates a subpopulation of highly procoagulant 'coated' platelets characterized
      by high surface expression of fibrinogen and other procoagulant proteins.
      OBJECTIVES: To analyze the interaction of recombinant factor VIIa (rFVIIa) with
      coated platelets. METHODS AND RESULTS: rFVIIa localized to the coated platelets
      in flow cytometry experiments, while minimal rFVIIa was found on platelets
      activated with adenosine diphosphate, thrombin or via glycoprotein VI
      individually, and essentially no rFVIIa was found on non-stimulated platelets.
      Removal of the gamma-carboxyglutamic acid (Gla) domain of rFVIIa, and addition of
      EDTA, annexin V or excess prothrombin inhibited rFVIIa localization to the coated
      platelets, indicating that the interaction was mediated by the calcium-dependent
      conformation of the Gla domain and platelet exposure of negatively charged
      phospholipids. A reduced level of platelet fibrinogen exposure was observed at
      hemophilia A-like conditions in a model system of cell-based coagulation,
      indicating that coated platelet formation in hemophilia may be diminished.
      Addition of rFVIIa dose-dependently enhanced thrombin generation and partly
      restored platelet fibrinogen exposure. CONCLUSIONS: The data suggest that rFVIIa
      localized preferentially on platelets activated with dual agonists, thereby
      ensuring enhanced thrombin generation localized at the site of injury where both
      collagen and tissue factor are exposed, the latter ensuring the formation of
      thrombin necessary for coated platelet formation.

PMID- 17229059
TI  - Identification of genes displaying differential expression in the nuc-2 mutant
      strain of the mold Neurospora crassa grown under phosphate starvation.
AB  - Subtractive hybridization was used to isolate transcripts up-regulated in the nuc
      2 mutant strain of Neurospora crassa grown under phosphate starvation. Following
      differential screening, 66 cDNA clones of the total enriched were screened in a
      second round by reverse Northern hybridization. The 17 cDNA candidates displaying
      visual positive differential expression were sequenced, and functional grouping
      identified putative proteins possibly involved in diverse cellular processes as,
      for example, protein synthesis, signal transduction mechanisms, and transport
      facilitation. Four of them, confirmed by both virtual and Northern blot analyses,
      revealed genes involved in the initiation of mRNA translation that are
      significantly up-regulated in the nuc-2 mutant strain, which may be relevant to a
      further understanding of the molecular events involved in the phosphorus sensing
      in N. crassa.

PMID- 17229058
TI  - Specificity of catecholamine-induced growth in Escherichia coli O157:H7,
      Salmonella enterica and Yersinia enterocolitica.
AB  - The present study demonstrates that catecholamine responsiveness in Yersinia
      enterocolitica, a bacterial pathogen whose infectious spectrum is principally
      limited to the gut, is limited to norepinephrine and dopamine, and not
      epinephrine; this behavior contrasts with observations for two pathogens with a
      wider extra-gastrointestinal spectrum, Escherichia coli O157:H7 and Salmonella
      enterica, which respond to all three catecholamines. Epinephrine showed lower
      potency than norepinephrine and dopamine in inducing growth of E. coli and S.
      enterica, and was a potent antagonist of norepinephrine and dopamine growth
      responsiveness in Y. enterocolitica. Given that only norepinephrine and dopamine
      and not epinephrine-containing neurons are found with the enteric nervous system,
      the results suggest that certain of the more exclusive enteric pathogens may have
      developed response systems preferentially for those neuroendocrine hormones that
      are produced by the enteric nervous system as host-derived signals by which to
      sense the environment and initiate pathogenic processes.

PMID- 17229060
TI  - Fatty acids synthesized by oral treponemes in chemically defined media.
AB  - OMIZ-W68, a chemically defined medium that contains no long-chain fatty acids and
      yet supports in vitro proliferation of a wide range of fastidious oral anaerobes,
      is described. The type strains of Treponema denticola, Treponema
      lecithinolyticum, Treponema maltophilum, Treponema pectinovorum, Treponema
      socranskii, and an as yet unpublished canine Treponema species could be
      propagated indefinitely in this medium with sugar supplements for the
      saccharolytic species. Analysis of the cellular fatty acids (CFA) of these
      treponemes by gas chromatography demonstrated the synthesis of C14, C15, C16, and
      C17 fatty acids (linear-, iso-, and anteiso-forms) in various proportions, but
      neither hydroxy- nor unsaturated fatty acids. However, between 0% and 40% of the
      eluted material could not be identified. The proportions of CFAs differed not
      only between species but also between the eight strains of Treponema denticola
      investigated. Replacing OMIZ-W68 by a derivative minimal essential medium (OMIZ
      M/TDCDK) developed for Treponema denticola had little effect on the CFA profiles.
      In contrast, the CFA profiles of treponemes grown in OMIZ-W68 showed at best
      minor similarity to the strains from the Moore library of the Virginia
      Polytechnic Institute, which had been grown in media containing serum, peptones,
      and yeast extract.

PMID- 17229062
TI  - Quantitation of Guggenheimella bovis and treponemes in bovine tissues related to
      digital dermatitis.
AB  - Digital dermatitis is an inflammation of uncertain aetiology in the skin of the
      foot of cattle. In 2005, a novel microorganism, Guggenheimella bovis, was
      isolated from the advancing front of digital dermatitis lesions, suggesting a
      possible role in pathogenesis. In the present study, tissue samples of 20
      affected cows were examined by quantitative PCR for G. bovis, treponemes and the
      total eubacterial load. High numbers of eubacteria and treponemes were found in
      most lesions, whereas only a few lesions contained Guggenheimella, and only at
      low concentrations. The results argue against the relevance of G. bovis in the
      aetiology of digital dermatitis in cattle, but are consistent with a role for
      treponemes.

PMID- 17229061
TI  - Molecular typing of isolates of the fish pathogen, Flavobacterium columnare, by
      single-strand conformation polymorphism analysis.
AB  - Flavobacterium columnare intraspecies diversity was revealed by analyzing the 16S
      rRNA gene and the 16S-23S internal spacer region (ISR). Standard restriction
      fragment length polymorphism (RFLP) of these sequences was compared with single
      strand conformation polymorphism (SSCP). Diversity indexes showed that both 16S
      SSCP and ISR-SSCP improved resolution (D>or=0.9) when compared with standard
      RFLP. ISR-SSCP offered a simpler banding pattern than 16S-SSCP while providing
      high discrimination between isolates. SSCP analysis of rRNA genes proved to be a
      simple, rapid, and cost-effective method for routine fingerprinting of F.
      columnare.

PMID- 17229063
TI  - Genetic variation in comC, the gene encoding competence-stimulating peptide (CSP)
      in Streptococcus mutans.
AB  - The genetic variability in comC, the gene encoding the quorum-sensing molecule,
      competence-stimulating peptide (CSP) in Streptococcus mutans is reported. Seven
      comC alleles encoding three distinct mature CSPs were identified among 36
      geographically diverse strains, although, compared with Streptococcus pneumoniae,
      the amount of predicted amino acid sequence variation is low. In agreement with
      other studies, significant variation was found in the natural competence for DNA
      uptake in these strains. However, there was no correlation between the CSP
      genotype and the ability to transform these strains. Representative strains
      encoding each of the CSP variants became competent in response to synthetic CSPs
      of each type. Therefore, in contrast to S. pneumoniae, comC alleles in S. mutans
      are functionally equivalent and there is no evidence of pherotype specificity.

PMID- 17229065
TI  - The Institute of Medicine report: sensible and consequential.

PMID- 17229064
TI  - Analysis of single nucleotide polymorphisms in three genes shows evidence for
      genetic isolation of certain Aspergillus flavus vegetative compatibility groups.
AB  - Genetic exchange by asexual filamentous fungi is presumed to be limited to
      isolates in the same vegetative compatibility group (VCG). To evaluate genetic
      isolation of Aspergillus flavus due to vegetative incompatibility, three gene
      regions were chosen that contained closely spaced nucleotides that were
      polymorphic among some of the six VCGs examined. A member of each VCG was
      collected from five regions across the southern United States. Isolates belonging
      to the same VCG had similar sets of single nucleotide polymorphisms regardless of
      isolate origin. The six VCGs formed four genetically distinct groups. Although
      recombination between certain pairs of VCGs could not be excluded, none was found
      for YV36, the VCG that includes the atoxigenic A. flavus isolate currently used
      to mitigate aflatoxin contamination in cotton in Arizona.

PMID- 17229066
TI  - Mycophenolate mofetil/sirolimus compared to other common immunosuppressive
      regimens in kidney transplantation.
AB  - We evaluated outcomes with the sirolimus (SRL) and mycophenolate mofetil (MMF)
      combination regimen (SRL/MMF) in solitary kidney transplant recipients
      transplanted between 2000 and 2005 reported to the Scientific Registry of Renal
      Transplant Recipients. Three-and-a-half percent received SRL/MMF (n = 2040). Six
      month acute rejection rates were higher with SRL/MMF (SRL/MMF: 16.0% vs. other
      regimens: 11.2%, p < 0.001). Overall graft survival was significantly lower on
      SRL/MMF. SRL/MMF was associated with twice the hazard for graft loss (AHR = 2.0,
      95% C.I., 1.8, 2.2) relative to TAC/MMF, also consistent in both living donor
      transplants (AHR = 2.4, 95% C.I., 1.9, 2.9) and expanded criteria donor
      transplants (AHR = 2.1, 95% C.I., 1.7-2.5). Among deceased donor transplants, DGF
      rates were higher in the SRL/MMF cohort (47% vs. 27%, p < 0.001). However,
      adjusted graft survival was also significantly inferior with SRL/MMF in DGF-free
      patients (AHR = 1.9, 95% C.I., 1.6-2.3). In analyses restricted to patients who
      remained on the discharge regimen at 6 months posttransplant, conditional graft
      survival in deceased donor transplants was significantly lower with SRL/MMF
      compared to patients on TAC/MMF or CsA/MMF regimens at 5 years posttransplant
      (64%, 78%, 78%, respectively, p = 0.001) and across all patient subgroups. In
      conclusion, SRL/MMF is associated with inferior renal transplant outcomes
      compared with other commonly used regimens.

PMID- 17229067
TI  - Subclinical acute antibody-mediated rejection in positive crossmatch renal
      allografts.
AB  - Subclinical antibody-mediated rejection (AMR) has been described in renal
      allograft recipients with stable serum creatinine (SCr), however whether this
      leads to development of chronic allograft nephropathy (CAN) remains unknown. We
      retrospectively reviewed data from 83 patients who received HLA-incompatible
      renal allografts following desensitization to remove donor-specific antibodies
      (DSA). Ten patients had an allograft biopsy showing subclinical AMR [stable SCr,
      neutrophil margination in peritubular capillaries (PTC), diffuse PTC C4d,
      positive DSA] during the first year post-transplantation; 3 patients were treated
      with plasmapheresis and intravenous immunoglobulin. Three patients had a
      subsequent rise in SCr and an associated biopsy with AMR; 5 others showed
      diagnostic or possible subclinical AMR on a later protocol biopsy. One graft was
      lost, while remaining patients have normal or mildly elevated SCr 8-45 months
      post-transplantation. However, the mean increase in CAN score (cg + ci + ct + cv)
      from those biopsies showing subclinical AMR to follow-up biopsies 335 +/- 248
      (SD) days later was significantly greater (3.5 +/- 2.5 versus 1.0 +/- 2.0, p =
      0.01) than that in 24 recipients of HLA-incompatible grafts with no AMR over a
      similar interval (360 +/- 117 days), suggesting that subclinical AMR may
      contribute to development of CAN.

PMID- 17229068
TI  - Preoperative volume prediction in adult living donor liver transplantation: how
      much can we rely on it?
AB  - Accurate preoperative prediction of functional donor and remnant hemiliver
      volumes in live donor liver transplantation is essential in preventing
      postoperative liver failure and optimizing safety. Our aim was (1) to evaluate
      volume variability associated with multiphasic CT imaging and (2) to determine
      over- or under-estimations of 3-D CT graft-volume assessments based on 'largest'
      versus 'smallest' CT phases with respect to intraoperative findings. Native,
      arterial and venous phase CT images from 83 potential live liver donors were
      subject to 3-D CT liver volume calculations and virtual 3-D liver partitioning.
      Estimates were compared to intraoperative volumes obtained in 43 cases.
      Calculated (preoperative) graft-volume-body-weight-ratios (GVBWR) versus measured
      (intraoperative) graft-weight-body-weight-ratios (GWBWR) were analyzed.
      Significant differences in total liver volume- and in graft-liver volume
      calculations were found among the largest (venous) and smallest (native) CT
      phases. High significant overestimations were observed in graft-volume
      determinations and in GVBWR-calculations based on the 'largest' CT phase when
      compared to intraoperatively obtained graft-weight and -GWBWR values. In
      contrast, differences among intraoperative measurements and preoperative
      calculations based on the 'smallest' CT phase yielded less significant
      overestimations. While 3-D CT volumetry based on the 'largest' (venous) CT phase
      is associated with considerable overestimation, 3-D volumetry based on the
      'smallest' (native) CT phase accurately matches the intraoperative findings.

PMID- 17229069
TI  - Human islet oxygen consumption rate and DNA measurements predict diabetes
      reversal in nude mice.
AB  - There is a need for simple, quantitative and prospective assays for islet quality
      assessment that are predictive of islet transplantation outcome. The current
      state-of-the-art athymic nude mouse bioassay is costly, technically challenging
      and retrospective. In this study, we report on the ability of 2 parameters
      characterizing human islet quality: (1) oxygen consumption rate (OCR), a measure
      of viable volume; and (2) OCR/DNA, a measure of fractional viability, to predict
      diabetes reversal in nude mice. Results demonstrate that the probability for
      diabetes reversal increases as the graft's OCR/DNA and total OCR increase. For a
      given transplanted OCR dose, diabetes reversal is strongly dependent on OCR/DNA.
      The OCR and OCR/DNA (the 'OCR test') data exhibit 89% sensitivity and 77%
      specificity in predicting diabetes reversal in nude mice (n = 86). We conclude
      that the prospective OCR test can effectively replace the retrospective athymic
      nude mouse bioassay in assessing human islet quality prior to islet
      transplantation.

PMID- 17229070
TI  - Beneficial effects of CCR1 blockade on the progression of chronic renal allograft
      damage.
AB  - The biology of chemokines and their receptors have been linked to the development
      of chronic allograft damage. Effects of CCR1 antagonist BX 471 were studied in a
      Fischer to Lewis renal transplantation model at days 10, 21 and 42 after
      transplantation. BX 471 treatment did not effectively reduce signs of acute
      rejection at day 10 but significantly improved allograft function and morphology
      at day 21 posttransplantation. When therapy was initiated on day 21 after
      transplantation, glomerulosclerosis and tubulointerstitial fibrosis were
      significantly inhibited by day 42 posttransplantation. Parallel decrease in
      infiltrating and proliferating mononuclear cells (ED1, CD8 and Ki67) was observed
      in treated allografts. Expression of acute phase reactive and proinflammatory
      genes (HO-1, osteopontin) and molecules associated with fibrosis (PAI-1, TGF
      beta1, biglycan) was downregulated at day 21; reduced collagen deposition was
      observed, parallel to a significant lower number of alpha-SMA+ interstitial
      myofibroblasts. In situ hybridization demonstrated that biglycan expression was
      reduced following CCR1 blockade in interstitium of treated allografts. CCR1
      antagonism was found to inhibit CCL5-induced secretion of biglycan by macrophages
      in vitro. CCR1 blockade significantly inhibited development and progression of
      chronic allograft damage. CCR1 antagonists may represent a therapeutic option for
      chronic inflammation and fibrosis in renal grafts.

PMID- 17229071
TI  - The interface between coagulation and immunity.
AB  - Coagulation proteases are involved in generating fibrin after vascular injury
      (hemostasis) but they also have multiple other effects, many of which are
      mediated independently of fibrin generation, via interactions with specific cell
      membrane-expressed "protease activated receptors". In inflammation, this family
      of proteins has a complex influence, the facets of which are still incompletely
      understood, though a common feature in different models appears to be
      amplification of innate signals that are initially generated by pathogenic
      elements or, in the context of transplantation, ischemia or anti-graft
      antibodies, for instance. There is increasing evidence that these proteases may
      also have specific effects on cells involved in adaptive immunity and on cells
      that mediate chronic inflammation and fibrosis. Understanding whether these
      effects are relevant in the responses generated against transplanted organs is
      important, as it could lead ultimately to the development of novel ways to
      promote long-term graft survival.

PMID- 17229072
TI  - Improving patient education delivery to increase living donation rates.

PMID- 17229073
TI  - The interleukin-12 family: new players in transplantation immunity?
AB  - Since several years ago, interleukin (IL)-12 is known to be responsible for the
      differentiation of naive CD4+ T cells into type 1 helper T cells producing
      interferon-gamma. Recently, two other cytokines of the IL-12 family, IL-23 and IL
      27, were shown to play key roles in experimental autoimmune disorders mediated by
      Th17 cells, a novel pro-inflammatory CD4+ T-cell subset secreting IL-17. As our
      knowledge of IL-12 family members is rapidly growing and changing, it will be
      important to specify their involvement in the induction and regulation of
      allograft rejection in animal models as well as in clinical settings. Herein, we
      review key features of cytokines belonging to the IL-12 family and discuss their
      potential relevance to transplantation immunity.

PMID- 17229074
TI  - Epstein-Barr virus: evasive maneuvers in the development of PTLD.
AB  - Epstein-Barr virus (EBV) infection is linked to approximately 90% of B-cell
      lymphomas associated with posttransplant lymphoproliferative disease (PTLD), a
      serious complication for immunosuppressed transplant recipients. In this paper,
      we review the myriad ways by which EBV can inadvertently drive the genesis and
      persistence of B-cell lymphomas, particularly when the antiviral immune response
      is compromised. Probing the basic mechanisms by which EBV infection proceeds and
      contributes to malignancy in such cases will hopefully improve our understanding
      and treatment of PTLD and other EBV-associated malignancies.

PMID- 17229075
TI  - Ten-year experience in porto-caval hemitransposition for liver transplantation in
      the presence of portal vein thrombosis.
AB  - Porto-caval hemitransposition (PCH) in liver transplantation allows
      revascularization of the liver when the porto-mesenteric axis is thrombosed. We,
      here, review our experience over an 11-year period. A total of 23 patients
      underwent liver transplantation using PCH. Immunosuppression was based on
      tacrolimus, with sirolimus used in case of renal insufficiency. Most common
      diagnoses were hepatitis C, Laennec's, Budd-Chiari and cryptogenic cirrhosis. Six
      patients needed splenectomy prior to transplant, 5 during transplant, 1 post
      transplant, 11 had no splenectomy. Overall survival was 60% at 1 year and 38% at
      3 years, with 10 of 23 patients currently alive and the longest survivor at 9.3
      years. Most common cause of death was sepsis/multisystem organ failure, followed
      by pulmonary embolism. A total of 7/23 patients experienced post-operative
      gastrointestinal bleeding episodes, 6/23 patients developed thrombosis of the
      vena cava (median 162 days post-op). Post-operative ascites was noted in almost
      all patients. Renal dysfunction was commonly seen even after the first month post
      transplant. PCH offers a feasible option for liver transplantation in those
      patients with complex thrombosis of the mesenteric and portal circulation.

PMID- 17229077
TI  - Rho-associated kinase inhibitor reduces tumor recurrence after liver
      transplantation in a rat hepatoma model.
AB  - Tumor recurrence after liver transplantation still remains a significant problem
      in patients with hepatocellular carcinoma. The small GTPase Rho/Rho-associated
      kinase (ROCK) pathway is involved in the motility and invasiveness of cancer
      cells. We investigated whether tacrolimus activated the Rho/ROCK signal pathway
      to promote the invasiveness of rat hepatocellular carcinoma cells. We also
      investigated whether the ROCK inhibitor Y-27632 suppressed tumor recurrence after
      experimental liver transplantation in a rat hepatocellular carcinoma model.
      Orthotopic liver transplantation was performed in hepatocellular carcinoma cell
      line McA-RH7777-bearing rats. Tacrolimus was administered to liver transplant
      rats and these rats were divided into two groups: the Y-27632-treated (10 mg/kg,
      for 28 days) group and the Y-27632-untreated group. Tacrolimus enhanced the
      cancer cell migration and stimulated phosphorylation of the myosin light chain
      (MLC), a downstream effector of Rho/ROCK signaling. Y-27632 suppressed the cancer
      cell migration and tacrolimus-induced MLC phosphorylation. Suppression of tumor
      recurrence after liver transplantation and significant prolongation of survival
      were observed in the Y-27632-treated rats in comparison with theY-27632-untreated
      rats. Tacrolimus stimulates the Rho/ROCK signal pathway to enhance the
      invasiveness of hepatocellular carcinoma, and the ROCK inhibitor Y-27632 can be
      used as a new antimetastatic agent for the prevention of tumor recurrence after
      liver transplantation.

PMID- 17229076
TI  - Switching from tacrolimus to sirolimus halts the appearance of new sebaceous
      neoplasms in Muir-Torre syndrome.
AB  - Little is known about the effects of immunosuppression on patients with
      hereditary nonpolyposis colorectal cancer (HNPCC). We describe a kidney
      transplant recipient with unrecognized Muir-Torre syndrome in whom the
      administration of a tacrolimus-based regimen led to the eruption of multiple
      sebaceous tumors. The patient was later found to harbor an MSH2 mutation.
      Switching to a sirolimus-based regimen resulted in arrest of the disease. When
      the patient was switched back to tacrolimus, new facial lesions rapidly appeared.
      Switching again to sirolimus resulted again in halting the appearance of new
      lesions. This finding is in line with the known antiangiogenic activity of
      sirolimus and reports on the regression of cutaneous Kaposi's sarcoma in kidney
      transplant recipients switched from another immunosuppressive regimen to
      sirolimus. Further studies on the potential use of sirolimus for the treatment of
      de novo tumors in immunosuppressed kidney transplant recipients with HNPCC are
      warranted.

PMID- 17229078
TI  - Obesity, adiponectin and inflammation as predictors of new-onset diabetes
      mellitus after kidney transplantation.
AB  - The high incidence of new-onset diabetes mellitus after transplantation (NODAT)
      suggests the need to find new factors to explain the pathogenesis. Our objectives
      were (1) to confirm that low levels of pre-transplant adiponectin are an
      independent risk factor for the development of NODAT in a larger transplanted
      population; (2) to analyze whether adiponectin is a better predictor of NODAT
      than other inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6),
      tumor necrosis factor-alpha (TNF-alpha) and pregnancy-associated plasma protein A
      (PAPP-A)) and (3) to assess the relationship between obesity, inflammatory
      markers and NODAT. One hundred ninety-nine non-diabetic patients (128 men; age:
      53 +/- 11 years; body mass index (BMI) 24.98 +/- 3.76 kg/m2) were included. Pre
      transplant plasma glucose, insulin, adiponectin, CRP, TNF-alpha, IL-6 and PAPP-A
      were measured. Forty-five patients developed NODAT. Patients with NODAT had a
      greater BMI (p = 0.005). Adiponectin was lower (p < 0.001) and CRP higher (p =
      0.032) in patients with NODAT. Multivariate logistic regression and Cox analysis
      showed that the calcineurin inhibitor used, pre-transplant BMI and adiponectin
      were predictors of NODAT. ROC analysis showed that an adiponectin concentration
      of 11.4 microg/mL had a significant negative prediction for NODAT risk
      (sensitivity: 81% and specificity: 70%). Of the inflammatory markers studied,
      adiponectin proved to be an independent predictor of NODAT.

PMID- 17229079
TI  - Cyclosporine sparing with mycophenolate mofetil, daclizumab and corticosteroids
      in renal allograft recipients: the CAESAR Study.
AB  - Although the calcineurin inhibitors (CNI) cyclosporine (CsA) and tacrolimus are
      highly effective immunosuppressants, they are associated with serious side
      effects. There is great interest in immunosuppressive regimens that permit
      reduction or elimination of CNIs, while maintaining adequate immunosuppression
      and acceptable acute rejection rates. Patients (n = 536) receiving their first
      renal allograft were randomized to one of three immunosuppressant regimens:
      daclizumab, mycophenolate mofetil (MMF), corticosteroids (CS) and low-dose CsA
      (target trough levels of 50-100 ng/mL), weaned from month 4 and withdrawn by
      month 6; daclizumab, MMF, CS and low-dose CsA; or MMF, CS and standard-dose CsA.
      Mean GFR 12 months after transplantation (primary end point) was not
      statistically different in the CsA withdrawal and low-dose CsA groups (both 50.9
      mL/min/1.73 m(2)) vs. the standard-dose CsA group (48.6 mL/min/1.73 m(2)). At 12
      months, the incidence of biopsy-proven acute rejection was significantly higher
      in the CsA withdrawal group (38%) vs. the low- or standard-dose CsA groups (25.4%
      and 27.5%, respectively; p < 0.05). In summary, a regimen of continuous low-dose
      CsA with MMF, CS and daclizumab induction is a clinically safe and effective
      immunosuppressive regimen in renal transplant recipients.

PMID- 17229080
TI  - Four-year follow-up of a prospective trial of HLA and MICA antibodies on kidney
      graft survival.
AB  - In 2002, 1329 patients with functioning transplants were prospectively tested for
      HLA antibodies in the 13th International Histocompatibility Workshop. Four years
      after testing, deceased donor graft survival among 806 patients not having
      antibodies in 2002 was 81% compared to 58% for 158 patients with HLA antibodies
      (p < 0.0001) and 72% for 69 patients with MICA antibodies (p = 0.02). Hazard
      ratio (HR) using death-censored graft survival from multivariate analysis of HLA
      antibodies was 3.3 (p < 0.00001) and 2.04 for MICA (p = 0.01). In the 14th
      Workshop, at 1 year follow-up, survival for 1319 patients receiving deceased
      donor grafts and no HLA antibodies was 96% compared to 94% for 344 patients with
      HLA antibodies (p = 0.0004) and 83% survival for 33 patients with MICA (p =
      0.0005). HR from multivariate analysis: HLA antibodies was 3.6 (p < 0.00001) and
      6.1 for MICA (p = 0.006). Twelve patients with donor specific antibodies tested
      by single antigen beads had a 1 year survival of 64% (p = 0.008), and 27 patients
      with non-donor specific 'strong' antibodies had a 66% survival (p = 0.0003)
      compared to 92% survival in those with no antibodies. In conclusion, these two
      prospective trials, after 1 and 4 years, provided strong evidence that HLA and
      MICA antibodies are associated with graft failure.

PMID- 17229081
TI  - Cooperative effects of bcl-2 and AAV-mediated expression of CNTF on retinal
      ganglion cell survival and axonal regeneration in adult transgenic mice.
AB  - We used a gene therapy approach in transgenic mice to assess the cooperative
      effects of combining anti-apoptotic and growth-promoting stimuli on adult retinal
      ganglion cell (RGC) survival and axonal regeneration following intraorbital optic
      nerve injury. Bi-cistronic adeno-associated viral vectors encoding a secretable
      form of ciliary neurotrophic factor and green fluorescent protein (AAV-CNTF-GFP)
      were injected into eyes of mice that had been engineered to over-express the anti
      apoptotic protein bcl-2. For comparison this vector was also injected into
      wildtype (wt) mice, and both mouse strains were injected with control AAV
      encoding GFP. Five weeks after optic nerve injury we confirmed that bcl-2 over
      expression by itself promoted the survival of axotomized RGCs, but in contrast to
      previous reports we also saw regeneration of some mature RGC axons beyond the
      optic nerve crush. AAV-mediated expression of CNTF in adult retinas significantly
      increased the survival and axonal regeneration of RGCs following axotomy in wt
      and bcl-2 transgenic mice; however, the effects were greatest in the transgenic
      strain. Compared with AAV-GFP-injected bcl-2 mice, RGC viability was increased by
      about 50% (mean, 36 738 RGCs per retina), and over 1000 axons per optic nerve
      regenerated 1-1.5 mm beyond the crush. These findings exemplify the importance of
      using a multifactorial therapeutic approach that enhances both neuroprotection
      and regeneration after central nervous system injury.

PMID- 17229082
TI  - Urinary pheromones promote ERK/Akt phosphorylation, regeneration and survival of
      vomeronasal (V2R) neurons.
AB  - The G protein-coupled pheromone receptor neurons (V1R and V2R) of the vomeronasal
      organ (VNO) are continually replaced throughout the lifetime of the mouse.
      Moreover, active signalling of V2Rs via the transient receptor potential 2(TRPC2)
      channel is necessary for regeneration of receptors, as the TRPC2 null mutant
      mouse showed a 75% reduction of V2Rs by the age of two months. Here we describe
      V2R mediated signalling in a neuronal line established from vomeronasal stem
      cells taken from postnatal female mice. Cells were immunoreactive for Galpha(o)
      and V2R, whereas V1R and Galpha(i) immunoreactivity could not be detected.
      Biological ligands (dilute urine and its protein fractions) were found to
      increase proliferation and survival of these neurons. Dilute mouse urine but not
      artificial urine also induced ERK, Akt and CREB signalling in a dose dependent
      way. The volatile fraction of male mouse urine alone was without effect while the
      fraction containing peptides (> 5 kDa) also stimulated ERK and Akt
      phosphorylation. The ERK, Akt and CREB phosphorylation response was sensitive to
      pertussis toxin, confirming the involvement of V2R linked Galpha(o). Dilute mouse
      urine or its high molecular weight protein fraction increased survival and
      proliferation of these neurons. Hence, urinary pheromones, which signal important
      social information via mature neurons, also promote survival and proliferation of
      their regenerating precursors. These data show that regenerating V2Rs respond to
      urine and the urinary peptides by activation of the Ras-ERK and PI3-Akt pathways,
      which appear to be important for vomeronasal neural survival and proliferation.

PMID- 17229083
TI  - Riluzole promotes cell survival and neurite outgrowth in rat sensory neurones in
      vitro.
AB  - This study explored the effects of riluzole administration on cell survival and
      neurite growth in adult and neonatal rat dorsal root ganglion (DRG) neurones in
      vitro. Neuronal survival was assessed by comparing numbers of remaining neurones
      in vehicle- and riluzole-treated cultures. A single dose of 0.1 microm riluzole
      was sufficient to promote neuronal survival in neonatal DRG cultures, whereas
      repeated riluzole administration was necessary in adult cultures. However, a
      single administration of riluzole was sufficient to induce neuritogenesis,
      promote neurite branching and enhance neurite outgrowth in both neonatal and
      adult DRG cultures. The effects of a single dose of riluzole on adult DRG
      neurones after peripheral nerve or dorsal root injury were also studied in vitro
      at 48 h. For both types of injury, riluzole enhanced neurite outgrowth in terms
      of number, length and branch pattern significantly more on the injured side as
      compared with the contralateral side. No effect was seen on cell survival. The
      results suggest that, in addition to its cell survival effects, riluzole has
      novel growth-promoting effects on sensory neurones in vitro and that riluzole may
      offer a new way to promote sensory afferent regeneration following peripheral
      injury.

PMID- 17229084
TI  - Chronic treatment with high doses of corticosterone decreases cytoskeletal
      proteins in the rat hippocampus.
AB  - Hypercortisolism is a common trait of Cushing's disease and depression. These two
      disorders also share hippocampal volume decrease and cognitive deficits. However,
      experimentally induced hypercortisolism induces neuronal atrophy, which has been
      proposed to be the phenomenon underlying the hippocampal shrinkage. We
      hypothesized that the above-mentioned atrophy is due to a deleterious effect of
      high concentrations of glucocorticoids on cytoskeletal proteins. One or two
      pellets (100 mg each) of corticosterone were subcutaneously implanted in adult
      rats. Twenty-one days later, light, medium and heavy subunits of intermediate
      neurofilaments (NFL, NFM and NFH) and the microtubule-associated protein 2 (MAP2)
      were quantified by immunohistochemistry in Ammon's horn and dentate gyrus. We
      also evaluated the in vitro glutamate release in hippocampal slices. Both doses
      of corticosterone induced a decrement of NFL, NFM and NFH in both hippocampal
      areas but only 200 mg decreased MAP2. This dose also diminished the potassium
      stimulated glutamate release. All of these changes seemed not to be due to neuron
      loss, as no decrement in neuron-specific nuclear protein-positive cells was
      found. With the exception of NFL, the above-mentioned diminution was not observed
      in the globus pallidus, one of the brain regions with the lowest glucocorticoid
      receptor density. These results provide a subcellular insight into the trophic
      changes found in experimental models of hypercortisolism. The coincidence between
      decrements in MAP2 and glutamate release suggests possible links between high
      glucocorticoid levels, dendritic atrophy and the cognitive impairment reported in
      patients suffering from Cushing's disease and depression.

PMID- 17229085
TI  - Enhanced cochlear acoustic sensitivity and susceptibility to endotoxin are
      induced by adrenalectomy and reversed by corticosterone supplementation in rat.
AB  - Glucocorticoid receptors are widely distributed in the cochlea but their role
      remains poorly known. Previous studies provided contradictory reports on a
      possible cochlear acoustic hypersensitivity induced by adrenal insufficiency,
      while several experiments agree on a significant action of glucocorticoid
      receptors in adverse conditions such as acoustic trauma and restraint stress. The
      present experiments confirmed a cochlear acoustic hypersensitivity induced by
      adrenalectomy and reversed by corticosterone supplementation. These observations
      point to a significant role of corticosteroids in basal cochlear functioning. The
      glucocorticoids are known to be essential for limiting and resolving inflammatory
      processes. The endotoxin Escherichia coli lipopolysaccharide is widely used to
      induce inflammatory reactions. However, in various organs several toxic processes
      of this endotoxin are not influenced by glucocorticoids. From previous
      experiments on the cochlea there is no evidence that glucocorticoids are an
      essential factor against endotoxin cochlear toxicity. In the present experiments
      it was found that adrenalectomy greatly increased the cochlear susceptibility to
      endotoxin; the effect was reversed by providing corticosterone supplementation.
      This shows the essential role of corticosterone in this cochlear inflammation
      model. In previous studies local administration (at the cochlear base) of
      endotoxin was used and losses of cochlear acoustic sensitivity were found
      predominantly at high frequencies; in contrast, the systemic injection used in
      this study produced a cochlear loss of acoustic sensitivity at all frequencies,
      indicating a uniform cochlear sensitivity to the toxic effects of endotoxin.

PMID- 17229086
TI  - Differential expression of otoferlin in brain, vestibular system, immature and
      mature cochlea of the rat.
AB  - Mutations of the human otoferlin gene lead to an autosomal recessive nonsyndromic
      form of prelingual, sensorineural deafness (deafness autosomal recessive 9,
      DFNB9). Several studies have demonstrated expression of otoferlin in the inner
      ear and brain, and suggested a role of otoferlin in Ca(2+)-triggered exocytosis.
      So far, otoferlin expression profiles were solely based on the detection of mRNA.
      Here, we analysed the expression of otoferlin protein and mRNA using
      immunohistochemistry, in situ hybridization and RT-PCR in neonatal and mature
      Wistar rat tissue. In agreement with previous studies, otoferlin expression was
      found in the brain and in inner and vestibular hair cells. Otoferlin mRNA and
      protein was, however, also detected in mature outer hair cells of low-frequency
      processing cochlear turns and in auditory nerve fibres. In outer, inner and
      vestibular hair cells, otoferlin was subcellularly localized at a considerable
      distance from the presumed active release sites. Double-staining with the
      synaptic ribbon marker, C-terminal binding protein 2 (CtBP2), or the presynaptic
      Ca(2+)-channel, Ca(v)1.3, both assumed to mark the sites of vesicle fusion and
      transmitter release, did not colocalize with otoferlin expression and thus do not
      necessarily support a selected role of otoferlin in Ca(2+)-triggered exocytosis.
      The widespread distribution of otoferlin in neurons, nerve fibres and hair cells,
      and its subcellular distribution extending beyond the regions of synaptic vesicle
      fusion, i.e. coenrichment with the cytosolic Golgi matrix protein 130 (GM130) in
      inner hair cells or the early endosomal autoantigen 1 (EEA1) in outer hair cells
      support instead the idea of a more ubiquitous role of otoferlin in
      early/recycling endosome trans-Golgi network dynamics.

PMID- 17229087
TI  - Cytosolic phospholipase A alpha modulates NMDA neurotoxicity in mouse hippocampal
      cultures.
AB  - The arachidonic acid-specific cytosolic phospholipase A(2) alpha (cPLA(2)alpha)
      has been implicated in the generation of neurological injuries. cPLA(2)alpha
      dependent neurological injury has been postulated to be mediated through
      inflammatory and eicosanoid pathways. We determined if cPLA(2)alpha amplifies the
      injury of a non-inflammatory, excitotoxic stimulus by modifying a well-described
      toxicity assay to measure the toxicity of N-methyl-d-aspartate (NMDA) in the CA1
      region of organotypic, mouse hippocampal cultures. Hippocampal cultures from wild
      type and cPLA(2)alpha knockout mice were exposed to 5, 7.5 or 10 microm NMDA for
      1 h. Toxicity was measured 23 h later. Cultures derived from cPLA(2)alpha(-/-)
      mice and cultures treated with the selective inhibitor AACOCF(3) were
      significantly protected from NMDA toxicity, as compared with wild-type cultures.
      To determine if cPLA(2)alpha-dependent toxicity is cyclooxygenase (COX)-2
      dependent, COX-2 and PGE(2) levels were measured 7 and 25 h after NMDA treatment.
      NMDA treatment failed to induce COX-2 protein or increase PGE(2) in the culture
      media in either genotype at either time. In contrast, phorbol 12-myristate 13
      acetate and ionophore treatment caused robust induction of COX-2 and PGE(2) in
      both genotypes. We conclude that cPLA(2)alpha may have a hitherto unrecognized
      direct effect on excitatory neurotoxicity, suggesting that cPLA(2)alpha
      inhibition is a therapeutic candidate for treatment of the early, excitotoxic
      injury observed in stroke.

PMID- 17229088
TI  - GSK3alpha exhibits beta-catenin and tau directed kinase activities that are
      modulated by Wnt.
AB  - In the presence of a Wnt signal beta-catenin is spared from proteasomal
      degradation through a complex mechanism involving GSK3beta, resulting in the
      transcription of Wnt target genes. In this study we have explored whether
      GSK3alpha, a related isoform, can also regulate nuclear beta-catenin levels and
      whether this and the tau-directed kinase activity of GSK3alpha are modulated by
      Wnt. GSK3alpha or GSK3beta and their substrates, beta-catenin and tau, were
      transiently expressed in mammalian cells. Immunoblotting revealed that GSK3alpha
      reduces nuclear levels of beta-catenin, whilst reporter gene assays demonstrated
      that GSK3alpha inhibits beta-catenin-directed Tcf/Lef-dependent transcription.
      Moreover, activation of the Wnt pathway was found to attenuate both the beta
      catenin- and the tau-directed kinase activities of GSK3alpha and GSK3beta. By
      immunoprecipitation we also found that axin-1, the beta-catenin destruction
      complex scaffold protein, binds GSK3alpha. In the light of these findings
      GSK3alpha warrants further investigation regarding its involvement in Wnt
      signalling and tauopathies such as Alzheimer's disease.

PMID- 17229089
TI  - Degeneration of noradrenergic fibres from the locus coeruleus causes tight
      junction disorganisation in the rat brain.
AB  - Although functional studies demonstrate that noradrenaline controls the
      permeability of the blood-brain barrier, it has never been determined whether
      this neurotransmitter regulates the tight junction (TJ) assembly that confers the
      barrier property to brain microvessels. We thus tested in rats the effect of
      pharmacological depletion of noradrenaline with the noradrenergic toxin DSP4 (5
      mg/kg) on the expression of the TJ proteins zonula occludens-1 (ZO1) and
      occludin. The effectiveness of the lesion was confirmed by tyrosine hydroxylase
      immunoreactivity, which showed noradrenergic fibre reduction accompanied by
      debris and swollen fibres in DSP4-treated brains. Noradrenergic fibre
      degeneration caused: (i) gliosis; (ii) disappearance of TJ proteins in vascular
      cell-to-cell contacts (49.9 and 38.3% reductions for occludin and ZO1,
      respectively); (iii) a 49.2% decrease in total ZO1 protein, measured by Western
      blot analysis, parallel to a 39.5% decrease in ZO1 mRNA, measured by real-time
      PCR; and (iv) a relative increase in the beta occludin isoform (62.9%), with no
      change in total occludin protein or mRNA. The expression of endothelial brain
      antigen, a marker of a functionally competent brain endothelium, was also
      reduced. We conclude that damage to the ascending fibres from the locus coeruleus
      caused TJ disruption and gliosis, a sign of inflammation. These results imply
      that the locus coeruleus degeneration reported in Alzheimer's and Parkinson's
      diseases may contribute to these disorders by causing blood-brain barrier
      dysfunction. Whether the vascular damage is the result of impaired noradrenergic
      transmission or secondary to the inflammatory reaction remains to be determined.

PMID- 17229090
TI  - Role of the calcium modulated cyclases in the development of the retinal
      projections.
AB  - Transmembrane isoforms of adenylate cyclases (AC) integrate a wide variety of
      extracellular signals from neurotransmitters to morphogens and can also regulate
      cAMP production in response to calcium entry. Based on observations in the
      barrelless mouse strain, the Adcy1 gene (AC1) was involved in the segregation of
      binocular retinal inputs. To determine the potential role of other AC isoforms we
      localized the Adcy genes in the visual centres during development, using in situ
      hybridization. Six different AC subtypes were found in the developing retinal
      ganglion cell layer (RGC; AC1, AC2, AC3, AC5, AC8, and AC9), and three AC
      subtypes were expressed in the central brain targets, the dorsal lateral
      geniculate nucleus (AC1 and AC8), the ventral lateral geniculate nucleus (AC2 and
      AC8) and the superior colliculus (AC1, AC2, AC8). Using a genetic approach we
      tested the role of the calcium modulated cyclases AC1, AC5 and AC8 for the
      segregation retinal fibres. Ipsilateral retinal axons remained exuberant in the
      AC1(-/-) mice, with overlapping retinal projections from both eyes in the
      superior colliculus and the visual thalamus. These abnormalities were similar to
      those of barrelless mouse mutants. No abnormalities were detectable in the AC5(-/
      ) or the AC8(-/-) mice. Similar abnormalities were noted in the single AC1(-/-)
      and the AC1/AC8 double-knockout mice (DKO). Thus, only AC1 is required for the
      maturation of the retinal axon terminals whereas AC5 and AC8 are not needed. The
      specificity of AC1's action is linked to its cellular localization in the RGCs
      and to its distinctive functional profile, compared with the other cyclases
      expressed in the same cells.

PMID- 17229092
TI  - Expression of histamine receptors and effect of histamine in the rat carotid body
      chemoafferent pathway.
AB  - Chemosensory information from peripheral arterial oxygen sensors in the carotid
      body is relayed by petrosal ganglion neurons to the respiratory networks in the
      medulla oblongata. Biogenic amines, including histamine, released from glomus
      (type I) cells of the carotid body are considered to be primary transmitters in
      hypoxic chemosensitivity. Immunocytochemistry at light-and electron-microscopical
      levels, and RT-PCR, revealed the expression of histamine receptors 1 and 3 as
      well as histidine decarboxylase in the rat carotid body glomus cells and petrosal
      ganglion neurons. Histamine receptors 1 and 3, but not histidine decarboxylase,
      were also observed in the ventrolateral, intermediate and commissural subnuclei
      of the nucleus tractus solitarii in the medulla oblongata. In order to examine
      the possible role of histamine in the afferent branch of the respiratory system,
      we applied histamine receptor 1 and 3 agonists to the carotid body, which caused
      a mildly increased phrenic nerve activity in a working heart-brainstem
      preparation. Moreover, microinjection of antagonists of histamine receptors 1 and
      3 into the nucleus tractus solitarii caused significant changes in the
      inspiratory timing and the chemoreceptor response. Our data show that histamine
      acting via histamine receptors 1 and 3 plays an important neuromodulatory role in
      the afferent control of chemosensitivity.

PMID- 17229093
TI  - Serial neurochemical measurement of cerebrospinal fluid during the human sexual
      response cycle.
AB  - Recent studies examining the neuroendocrine response pattern underlying the human
      sexual response cycle revealed transient activation of the sympathoadrenal system
      and a substantial, long-lasting increase in plasma prolactin concentrations
      following orgasm in men and women. Prolactin has been discussed as being part of
      a feedback mechanism that signals centers in the central nervous system, such as
      the dopaminergic system controlling sexual arousal. To further elucidate the
      central role of neuropeptides, biogenic monoamines and neurotransmitters in human
      sexual behavior, a serial cerebrospinal fluid (CSF)-sampling technique was
      implemented using a previously established experimental paradigm for sexual
      activity in a laboratory setting. In parallel with peripheral endocrine measures,
      lumbar CSF was drawn via an indwelling spinal catheter during the sexual response
      cycle in 10 healthy males and 10 age-matched controls, and analysed for
      prolactin, oxytocin, biogenic monoamines and/or their metabolites as well as
      inhibitory and excitatory neurotransmitter concentrations. Parallel to raised
      peripheral sympathetic activity, norepinephrine also increased in CSF during
      audiovisual, masturbation-induced sexual arousal and orgasm, and remained
      elevated for the remainder of the session (F(4,72) = 8.79, P = 0.000). In
      contrast, none of the other measures, in particular prolactin and dopamine or its
      metabolites, reflected significant alteration. In conclusion, the human sexual
      response cycle is characterized by an increase in sympathetic activity in plasma
      and CSF, and by pronounced secretion of plasma prolactin after orgasm. However,
      alterations in dopaminergic or peptidergic activity are not found in lumbar CSF,
      possibly due to local and restricted release in diencephalic and mesencephalic
      brain regions.

PMID- 17229094
TI  - Modulation of isolated N-methyl-d-aspartate receptor response under hyperbaric
      conditions.
AB  - In humans, hyperbaric pressure induces the high-pressure neurological syndrome
      (HPNS). HPNS is characterized by tremor, sleep disorders, electroencephalographic
      changes, and impairment of cognitive and motor performances. In animals, higher
      pressures result in convulsions and death. An increased N-methyl-d-aspartate
      receptor (NMDAR) response has been implicated with HPNS. We studied high-pressure
      effects on pharmacologically isolated NMDAR field excitatory postsynaptic
      potentials (fEPSPs). Hippocampal coronal brain slices from male Sprague-Dawley
      rats were prepared, constantly superfused with physiological solutions, gas
      saturated at normobaric pressure and compressed up to 10.1 MPa with helium.
      fEPSPs were recorded from the dendritic layer of CA1 pyramidal neurones. High
      pressure significantly increased the single fEPSP delay, maximal initial slope,
      amplitude, decay time and time integral (elevated Na(+) and Ca(2+) influx)
      despite the known general decrease in glutamatergic synaptic release. The
      estimated negative and positive activation volumes (DeltaV*) for various kinetic
      segments of the fEPSP suggest a complex response of the receptor to pressure. The
      NMDAR frequency response was tested by a train of five stimuli. At 50-100 Hz,
      high pressure did not increase the fEPSPs' frequency-dependent depression and the
      train's time integral remained unchanged. At 25 Hz, pressure induced a larger
      frequency-dependent depression and significantly increased the time integral. Our
      results provide, for the first time, direct information on the isolated brain
      NMDAR response under hyperbaric conditions. These observations may explain some
      increase in the excitability of single normal glutametergic fEPSPs and their
      frequency responses.

PMID- 17229091
TI  - Selective 5-HT receptor inhibition of glutamatergic and GABAergic synaptic
      activity in the rat dorsal and median raphe.
AB  - The dorsal (DR) and median (MR) raphe nuclei contain 5-hydroxytryptamine (5-HT)
      cell bodies that give rise to the majority of the ascending 5-HT projections to
      the forebrain. The DR and MR have differential roles in mediating stress, anxiety
      and depression. Glutamate and GABA activity sculpt putative 5-HT neuronal firing
      and 5-HT release in a seemingly differential manner in the MR and DR, yet
      isolated glutamate and GABA activity within the DR and MR has not been
      systematically characterized. Visualized whole-cell voltage-clamp techniques were
      used to record excitatory and inhibitory postsynaptic currents (EPSC and IPSC) in
      5-HT-containing neurons. There was a regional variation in action potential
      dependent (spontaneous) and basal [miniature (m)] glutamate and GABAergic
      activity. mEPSC activity was greater than mIPSC activity in the DR, whereas in
      the MR the mIPSC activity was greater. These differences in EPSC and IPSC
      frequency indicate that glutamatergic and GABAergic input have distinct
      cytoarchitectures in the DR and MR. 5-HT(1B) receptor activation decreased mEPSC
      frequency in the DR and the MR, but selectively inhibited mIPSC activity only in
      the MR. This finding, in concert with its previously described function as an
      autoreceptor, suggests that 5-HT(1B) receptors influence the ascending 5-HT
      system through multiple mechanisms. The disparity in organization and integration
      of glutamatergic and GABAergic input to DR and MR neurons and their regulation by
      5-HT(1B) receptors may contribute to the distinction in MR and DR regulation of
      forebrain regions and their differential function in the aetiology and
      pharmacological treatment of psychiatric disease states.

PMID- 17229095
TI  - Analysis of synaptic ultrastructure without fixative using high-pressure freezing
      and tomography.
AB  - Electron microscopy allows the analysis of synaptic ultrastructure and its
      modifications during learning or in pathological conditions. However,
      conventional electron microscopy uses aldehyde fixatives that alter the
      morphology of the synapse by changing osmolarity and collapsing its molecular
      components. We have used high-pressure freezing (HPF) to capture within a few
      milliseconds structural features without aldehyde fixative, and thus to provide a
      snapshot of living synapses. CA1 hippocampal area slices from P21 rats were
      frozen at -173 degrees C under high pressure to reduce crystal formation, and
      synapses on dendritic spines were analysed after cryosubstitution and embedding.
      Synaptic terminals were larger than after aldehyde fixation, and synaptic
      vesicles in these terminals were less densely packed. Small filaments linked the
      vesicles in subgroups. The postsynaptic densities (PSDs) exhibited filamentous
      projections extending into the spine cytoplasm. Tomographic analysis showed that
      these projections were connected with the spine cytoskeletal meshwork. Using
      immunocytochemistry, we found as expected GluR1 at the synaptic cleft and CaMKII
      in the PSD. Actin immunoreactivity (IR) labelled the cytoskeletal meshwork
      beneath the filamentous projections, but was very scarce within the PSD itself.
      ProSAP2/Shank3, cortactin and Ena/VASP-IRs were concentrated on the cytoplasmic
      face of the PSD, at the level of the PSD projections. Synaptic ultrastructure
      after HPF was different from that observed after aldehyde fixative. The boutons
      were larger, and filamentous components were preserved. Particularly, filamentous
      projections were observed linking the PSD to the actin cytoskeleton. Thus,
      synaptic ultrastructure can be analysed under more realistic conditions following
      HPF.

PMID- 17229096
TI  - Estradiol stimulates progenitor cell division in the ventricular and
      subventricular zones of the embryonic neocortex.
AB  - Two distinct populations of cerebral cortical progenitor cells that generate
      neurons during embryogenesis have been identified: radial glial cells and
      intermediate progenitor cells. Despite advances in our understanding of
      progenitor cell populations, we know relatively little about factors that
      regulate their proliferative behaviour. 17-beta-Estradiol (E2) is present in the
      adult and developing mammalian brain, and plays an important role in central
      nervous system processes such as neuronal differentiation, survival and
      plasticity. E2 also stimulates neurogenesis in the adult dentate gyrus. We
      examined the role of E2 during embryonic cortical neurogenesis through
      immunohistochemistry, in situ hybridization, functional enzyme assay, organotypic
      culture and in utero administration of estradiol-blocking agents in mice. We show
      that aromatase, the E2 synthesizing enzyme, is present in the embryonic
      neocortex, that estrogen receptor-alpha is present in progenitor cells during
      cortical neurogenesis, that in vitro E2 administration rapidly promotes
      proliferation, and that in utero blockade of estrogen receptors decreases
      proliferation of embryonic cortical progenitor cells. Furthermore, the E2
      inhibitor alpha-fetoprotein is expressed at high levels by radial glial cells but
      at lower levels by intermediate progenitor cells, suggesting that E2
      differentially influences the proliferation of these cortical progenitor cell
      types. These findings demonstrate a new functional role for E2 as a proliferative
      agent during critical stages of cerebral cortex development.

PMID- 17229097
TI  - Effects of inhibition of fatty acid amide hydrolase vs. the anandamide membrane
      transporter on TRPV1-mediated calcium responses in adult DRG neurons; the role of
      CB receptors.
AB  - The aim of the present study was to investigate the relationship between TRPV1
      stimulation and endocannabinoid-driven CB(1) receptor-mediated inhibition of
      activity in adult rat dorsal root ganglion (DRG) neurons, a model of primary
      afferent nociceptors. Calcium-imaging studies were performed to compare the
      effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597 (1 microm) vs.
      the anandamide (AEA) uptake inhibitor UCM707 (1 microm) on capsaicin (100 nm) and
      N-arachidonoyl dopamine (NADA; 1 microm)-evoked changes in intracellular calcium
      [Ca(2+)](i) in DRG neurons. The ability of the CB(1) receptor antagonist AM251 (1
      microm) to modulate the effects of URB597 and UCM707 was also determined.
      Suprafusion of NADA and capsaicin evoked robust increases in [Ca(2+)](i) in DRG
      neurons (89 +/- 4% and 132 +/- 6% of the depolarizing KCl response,
      respectively). Co-incubation with URB597 significantly attenuated both NADA and
      capsaicin-evoked increases in [Ca(2+)](i) (39 +/- 3% and 79 +/- 4% of KCl
      response, respectively). Similarly, co-incubation with UCM707 significantly
      attenuated both NADA and capsaicin-evoked increases in [Ca(2+)](i) (59 +/- 7% and
      72 +/- 4% of KCl response, respectively). The CB(1) receptor antagonist AM251
      significantly attenuated the effects of URB597 on NADA-evoked increases in
      [Ca(2+)](i) but not the effects of URB597 on capsaicin-evoked increases in
      [Ca(2+)](i). By contrast, AM251 significantly attenuated the inhibitory effects
      of UCM707 on both NADA and capsaicin-evoked increases in [Ca(2+)](i.) These data
      suggest that transport of both NADA and capsaicin into DRG neurons and the
      subsequent activation of TRPV1 is partly governed by FAAH-dependent mechanisms as
      well as via the putative AEA membrane transporter.

PMID- 17229098
TI  - Homeostatic plasticity during alcohol exposure promotes enlargement of dendritic
      spines.
AB  - Modifications of the size, shape and number of dendritic spines is thought to be
      an important component of activity-dependent changes of neuronal circuits, and
      may play an important role in the plasticity of drug addiction. The present study
      examined whether homeostatic increases in synaptic N-methyl-d-aspartate (NMDA)
      receptors in response to chronic ethanol exposure is associated with
      corresponding morphological changes in dendritic spines. Prolonged exposure of
      rat hippocampal cultures to either the NMDA receptor antagonist d(-)-2-amino-5
      phosphono-pentanoic acid or to ethanol increased punctate staining of F-actin and
      the postsynaptic density protein-95 (PSD-95). The increase in dendritic F-actin
      occurred only with clusters that co-localized with PSD-95 clusters, indicating
      that these actin structures likely represent dendritic spines. The ethanol
      induced increases in PSD-95 and F-actin clusters were activity-dependent and
      reversible. Finally, inhibition of protein palmitoylation prevented ethanol
      induced increases in synaptic NMDA receptor clustering and F-actin without
      altering the basal clustering of either F-actin or PSD-95. These observations
      support a model in which chronic ethanol exposure induces homeostatic increases
      of NR2B-containing NMDA receptors and PSD-95 to the postsynaptic density. This in
      turn may provide a scaffolding platform for the subsequent recruitment of actin
      signaling cascades that alter actin cycling and promote spine enlargement.

PMID- 17229099
TI  - Homeostatic control of the excitation-inhibition balance in cortical layer 5
      pyramidal neurons.
AB  - Homeostatic regulation in the brain is thought to be achieved through a control
      of the synaptic strength by close interactions between excitation and inhibition
      in cortical circuits. We recorded in a layer 5 pyramidal neuron of rat cortex the
      composite response to an electrical stimulation of various layers (2-3, 4 or 6).
      Decomposition of the global conductance change in its excitatory and inhibitory
      components permits a direct measurement of excitation-inhibition (E-I) balance.
      Whatever the stimulated layer was, afferent inputs led to a conductance change
      consisting of 20% excitation and 80% inhibition. Changing synaptic strengths in
      cortical networks by using a high-frequency of stimulation (HFS) protocol or a
      low-frequency of stimulation (LFS) protocol (classically used to induce long-term
      potentiation or long-term depression at the synaptic level) were checked in order
      to disrupt this balance. Application of HFS protocols in layers 2-3, 4 or 6, or
      of LFS protocols in layer 4 induced, respectively, long-term paralleled increases
      or long-term paralleled decreases in E and I which did not change the E-I
      balance. LFS protocols in layers 2-3 or 6 decreased E but not I and disrupted the
      balance. It is proposed that regulatory mechanisms might be mainly sustained by
      recurrent connectivity between excitatory and inhibitory neuronal circuits and by
      modulation of shunting GABA(A) inhibition in the layer 5 pyramidal neuron.

PMID- 17229100
TI  - Reduced presynaptic efficiency of excitatory synaptic transmission impairs LTP in
      the visual cortex of BDNF-heterozygous mice.
AB  - The neurotrophin brain-derived neurotrophic factor (BDNF) plays an important role
      in neuronal survival, axonal and dendritic growth and synapse formation. BDNF has
      also been reported to mediate visual cortex plasticity. Here we studied the
      cellular mechanisms of BDNF-mediated changes in synaptic plasticity, excitatory
      synaptic transmission and long-term potentiation (LTP) in the visual cortex of
      heterozygous BDNF-knockout mice (BDNF(+/-)). Patch-clamp recordings in slices
      showed an approximately 50% reduction in the frequency of miniature excitatory
      postsynaptic currents (mEPSCs) compared to wild-type animals, in the absence of
      changes in mEPSC amplitudes. A presynaptic impairment of excitatory synapses from
      BDNF(+/-) mice was further indicated by decreased paired-pulse ratio and faster
      synaptic fatigue upon prolonged repetitive stimulation at 40 Hz. In accordance,
      presynaptic theta-burst stimulation (TBS) failed to induce LTP at layer IV to
      layers II-III synapses during extracellular field-potential recordings in BDNF(+/
      ) animals. Changes in postsynaptic function could not be detected, as no changes
      were observed in either the amplitudes of evoked EPSCs, the ratios of AMPA : NMDA
      currents or the kinetics of evoked AMPA and NMDA EPSCs. In line with this
      observation, an LTP pairing paradigm that relies on direct postsynaptic
      depolarization under patch-clamp conditions could be induced successfully in
      BDNF(+/-) animals. These data suggest that a chronic reduction in the expression
      of BDNF to nearly 50% attenuates the efficiency of presynaptic glutamate release
      in response to repetitive stimulation, thereby impairing presynaptically evoked
      LTP in the visual cortex.

PMID- 17229101
TI  - Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine
      reinforcement in rats.
AB  - Although nicotine is considered to be responsible for the addictive properties of
      tobacco, growing evidence underlines the importance of non-nicotine components in
      smoking reinforcement. It has been shown that tobacco smoke contains monoamine
      oxidase (MAO) A and B inhibitors and decreases MAO-A and MAO-B activity in
      smokers. Here, we investigated the effects of clorgyline hydrochloride
      (irreversible MAO-A inhibitor; 2 mg/kg/day), selegiline (irreversible MAO-B
      inhibitor; 4 mg/kg) and the beta-carboline norharmane hydrochloride (reversible
      MAO-B inhibitor; 5 mg/kg/day) treatments on nicotine self-administration (30
      microg/kg/infusion, free base) in rats. Independent of the responsiveness to
      novelty and locomotor activity stimulation, only clorgyline hydrochloride
      treatment increased the intake of nicotine in a fixed-ratio schedule (FR5) of
      reinforcement. When a progressive-ratio schedule was implemented, both clorgyline
      hydrochloride and norharmane hydrochloride treatments potentiated the reinforcing
      effects of nicotine, whereas selegiline had no effect. Taken together, these
      results indicate that MAO-A inhibition interacts with nicotine to enhance its
      rewarding effects in rats and suggest that other compounds present in tobacco,
      such as beta-carboline, may also play an important role in sustaining smoking
      behavior in humans.

PMID- 17229102
TI  - Chemosensory and steroid-responsive regions of the medial amygdala regulate
      distinct aspects of opposite-sex odor preference in male Syrian hamsters.
AB  - In rodent species, such as the Syrian hamster, the expression of sexual
      preference requires neural integration of social chemosensory signals and steroid
      hormone cues. Although anatomical data suggest that separate pathways within the
      nervous system process these two signals, the functional significance of this
      separation is not well understood. Specifically, within the medial amygdala, the
      anterior region (MEa) receives input from the olfactory bulbs and other
      chemosensory areas, whereas the posterodorsal region (MEpd) contains a dense
      population of steroid receptors and receives less substantial chemosensory input.
      Consequently, the MEa may subserve a primarily discriminative function, whereas
      the MEpd may mediate the permissive effects of sex steroids on sexual preference.
      To test these hypotheses, we measured preference and attraction to female and
      male odors in males with lesions of either the MEa or MEpd. In Experiment 1,
      lesions of either region eliminated opposite-sex odor preferences. Importantly,
      MEpd-lesioned males displayed decreased attraction toward female odors,
      suggesting decreased sexual motivation. In contrast, MEa-lesioned males displayed
      high levels of investigation of both male and female odors, suggesting an
      inability to categorize the relevance of the odor stimuli. In Experiment 2, we
      verified that both MEa- and MEpd-lesioned males could discriminate between female
      and male odors, thereby eliminating the possibility that the observed lack of
      preference reflected a sensory deficit. Taken together, these results suggest
      that both the MEa and MEpd are critical for the expression of opposite-sex odor
      preference, although they appear to mediate distinct aspects of this behavior.

PMID- 17229103
TI  - Long-term depression and associativity in rat primary motor cortex following
      thalamic stimulation.
AB  - Associativity is an attractive property of LTP in terms of its possible mechanism
      as a model for memory storage. In this study, we compare the effects of
      homosynaptic vs. associative stimulation on the induction of LTP and LTD in the
      neocortex of freely behaving rats. Using a callosal input to the motor cortex as
      a 'strong' input (one that potentiates reliably following homosynaptic
      stimulation), we paired activity of this pathway with a 'weak' thalamocortical
      pathway (one that does not potentiate when stimulated homosynaptically).
      Surprisingly, homosynaptic HFS caused a lasting depression of the field EPSP in
      the thalamocortical pathway. Analysis of this effect revealed that it was largely
      polysynaptic. Associative HFS (HFS applied to both pathways) not only failed to
      induce an LTP effect in the thalamocortical pathway, it increased the magnitude
      of the depression. Associative HFS did, however, facilitate LTP induction in the
      'strong' callosal pathway. When comparing the effects of homosynaptic and
      associative LTD induction (HFS on one pathway anticorrelated with LFS on the
      other), we found that both protocols induced a similar magnitude of depression.
      These results show that HFS applied to the thalamocortical pathway causes a
      depression and this depression is enhanced, not reversed, by associative pairing
      with a strong input.

PMID- 17229104
TI  - Calprotectin in microglia from frontal cortex is up-regulated in schizophrenia:
      evidence for an inflammatory process?
AB  - Schizophrenia is associated with a number of pathological changes, including
      alterations in levels of specific proteins. Calprotectin is a novel 36 kDa
      calcium-binding protein of the S100 family and appears to be a nonspecific marker
      of inflammation. Calprotectin has not previously been investigated in brain
      tissue. Samples of post-mortem brain tissue from Brodmann area 9 were obtained
      from prefrontal cortex from subjects with schizophrenia, bipolar affective
      disorder, major depression, and from controls. Calprotectin levels were
      determined by ELISA. To determine cellular localization, immunocytochemical and
      fluorescent double-labelling analyses were performed. Exogenous calprotectin was
      added to retinoic acid-differentiated human SH-SY5Y neuroblastoma cell cultures
      in order to investigate mechanisms of action of calprotectin. Calprotectin was
      detectable in all samples, and mean levels were noted to be highest in
      schizophrenic brains (P < 0.05) and lowest in controls. Levels were intermediate
      in bipolar affective disorder and major depression. Exogenous calprotectin
      appeared to induce dendritic extension in SH-SY5Y cell culture in a dose
      dependent manner. Calprotectin was found to be localized to microglia. These
      findings suggest that increased levels of calprotecitn in the brain may reflect
      inflammatory processes, which play a role in the pathogenesis of major
      psychiatric disorders. Furthermore, calprotectin may influence dendritic
      plasticity.

PMID- 17229105
TI  - Brain activity associated with fear renewal.
AB  - This is the first mapping study of the brain activity associated with the renewal
      of an extinguished conditioned response. Rats were given radiolabeled
      fluorodeoxyglucose, a glucose analog, to map brain effects of an extinguished
      tone during context-dependent renewal of conditioned fear. A tone conditioned
      stimulus was paired with a footshock unconditioned stimulus in a first context,
      followed by conditioned response extinction in a second context and conditioned
      response renewal in a third context. Control rats were treated identically,
      except that tone and shock were presented pseudorandomly. Compared with control
      subjects, rats with conditioned response renewal had increased tone-evoked
      fluorodeoxyglucose uptake in the auditory system (auditory cortex, medial
      geniculate, inferior colliculus and lateral lemniscal nuclei), as well as somatic
      and visceral sensory nuclei (external cuneate, spinal trigeminal, solitary tract
      and vestibular nuclei). In addition, perirhinal cortex, anterior lateral
      hypothalamus and ventrolateral periaqueductal gray showed conditioned response
      renewal effects. Brain-behavior correlations indicated that the activity of the
      external cuneate nucleus strongly predicted the conditioned response in the
      renewal group. It is suggested that context-dependent fear renewal is associated
      with (1) tone-evoked activation of the excitatory conditioned stimulus
      representation in the auditory system, (2) associative activation of the
      unconditioned stimulus representation in somatic and visceral sensory nuclei in
      the absence of the unconditioned stimulus, and (3) neural activation of the
      perirhinal cortex, hypothalamus and periaqueductal gray. These findings support
      Pavlov's stimulus-substitution theory as a neural mechanism contributing to the
      renewal effect.

PMID- 17229106
TI  - Neurogenic correlates of an olfactory discrimination task in the adult olfactory
      bulb.
AB  - In the main olfactory bulb, stimuli are coded within the spatio-temporal pattern
      of mitral cells' activity. Granule cells are interneurons that shape the mitral
      cells' activity, and are continuously generated in the adult main olfactory bulb.
      However, the role of granule cell renewal remains elusive. We show here that an
      associative olfactory discrimination task reduces the survival of newborn
      neurons. However, when the olfactory task involves perceptually related odorants,
      the learning process is slower and does not induce such a reduction in the number
      of new neurons. Mapping newborn cells within the granule cell layer of the main
      olfactory bulb reveals a clustered distribution that evolves with learning as a
      function of odorant similarity and partly overlaps with the immediate-early gene
      Zif268 expression pattern. These data provide insight into the functional
      mechanisms underlying olfactory discrimination learning, and promote the
      importance of neurogenesis as a cellular basis for the restructuring of odor
      images in the main olfactory bulb.

PMID- 17229107
TI  - Bandwidth determines modulatory effects of centrifugal pathways on cochlear
      hearing desensitization caused by loud sound.
AB  - Centrifugal olivocochlear (OC) pathways modulate cochlear hearing losses induced
      in cats by loud sounds varying in bandwidth from tones to clicks and noise bands,
      in a variety of conditions. The general effect, always to reduce hearing damage,
      can be a net effect resulting from complex interactions between OC subcomponents
      (crossed and uncrossed OC pathways). The interactions between these subcomponents
      vary with type of loud sound, suggesting that sound bandwidth may be important in
      determining how OC pathways modulate loud sound-induced hearing loss. This
      dependency was examined and here it is reported that OC pathways do not alter
      cochlear hearing losses caused by loud noise with a 2-kHz-wide bandwidth
      intermediate between the loud sounds of previous studies. Increasing stimulus
      bandwidth even slightly more, to use a loud 3.5-kHz-wide bandwidth noise as the
      damaging sound, once again revealed OC modulation of cochlear hearing loss. The
      fact that OC pathways do not modulate cochlear hearing losses induced by loud 2
      kHz-wide noise was demonstrated in three very different test conditions in which
      OC pathways modulate hearing losses caused by narrower or broader bandwidth
      sounds. This confirmed that the absence of centrifugal modulation of hearing loss
      to this particular sound was a robust phenomenon not related to test condition.
      The absence of overall centrifugal effects was also true at the level of
      subcomponent pathways; neither crossed nor uncrossed OC pathways individually
      modulated cochlear hearing losses to the loud 2-kHz-wide noise. This surprising
      frequency dependency has general implications for centrifugal modulation of
      cochlear responses.

PMID- 17229108
TI  - Periodicity and frequency coding in human auditory cortex.
AB  - Understanding the neural coding of pitch and frequency is fundamental to the
      understanding of speech comprehension, music perception and the segregation of
      concurrent sound sources. Neuroimaging has made important contributions to
      defining the pattern of frequency sensitivity in humans. However, the precise way
      in which pitch sensitivity relates to these frequency-dependent regions remains
      unclear. Single-frequency tones also cannot be used to test this hypothesis as
      their pitch always equals their frequency. Here, temporal pitch (periodicity) and
      frequency coding were dissociated using stimuli that were bandpassed in different
      frequency spectra (centre frequencies 800 and 4500 Hz), yet were matched in their
      pitch characteristics. Cortical responses to both pitch-evoking stimuli typically
      occurred within a region that was also responsive to low frequencies. Its
      location extended across both primary and nonprimary auditory cortex. An
      additional control experiment demonstrated that this pitch-related effect was not
      simply caused by the generation of combination tones. Our findings support recent
      neurophysiological evidence for a cortical representation of pitch at the lateral
      border of the primary auditory cortex, while revealing new evidence that
      additional auditory fields are also likely to play a role in pitch coding.

PMID- 17229109
TI  - How does the brain mediate interpretation of incongruent auditory emotions? The
      neural response to prosody in the presence of conflicting lexico-semantic cues.
AB  - We frequently encounter conflicting emotion cues. This study examined how the
      neural response to emotional prosody differed in the presence of congruent and
      incongruent lexico-semantic cues. Two hypotheses were assessed: (i) decoding
      emotional prosody with conflicting lexico-semantic cues would activate brain
      regions associated with cognitive conflict (anterior cingulate and dorsolateral
      prefrontal cortex) or (ii) the increased attentional load of incongruent cues
      would modulate the activity of regions that decode emotional prosody (right
      lateral temporal cortex). While the participants indicated the emotion conveyed
      by prosody, functional magnetic resonance imaging data were acquired on a 3T
      scanner using blood oxygenation level-dependent contrast. Using SPM5, the
      response to congruent cues was contrasted with that to emotional prosody alone,
      as was the response to incongruent lexico-semantic cues (for the 'cognitive
      conflict' hypothesis). The right lateral temporal lobe region of interest
      analyses examined modulation of activity in this brain region between these two
      contrasts (for the 'prosody cortex' hypothesis). Dorsolateral prefrontal and
      anterior cingulate cortex activity was not observed, and neither was attentional
      modulation of activity in right lateral temporal cortex activity. However,
      decoding emotional prosody with incongruent lexico-semantic cues was strongly
      associated with left inferior frontal gyrus activity. This specialist form of
      conflict is therefore not processed by the brain using the same neural resources
      as non-affective cognitive conflict and neither can it be handled by associated
      sensory cortex alone. The recruitment of inferior frontal cortex may indicate
      increased semantic processing demands but other contributory functions of this
      region should be explored.

PMID- 17229111
TI  - Evidence for time-variant decision making.
AB  - Computational models based on diffusion processes have been proposed to account
      for human decision-making behaviour in a variety of tasks. The basic idea is that
      the brain keeps accumulating noisy sensory evidence until a critical level is
      reached. 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 simple diffusion model can explain the psychometric function and
      the mean response times of correct responses, it fails to account for the longer
      response times observed for errors and for the response time distributions. Here
      I demonstrate that a time-variant version of the diffusion model can explain the
      psychometric function, the mean response times and the shape of the response time
      distributions. Such a time-variant 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 gain of the sensory signals, which
      increases over time. 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. The results suggest that the brain trades off speed and accuracy not
      only by adjusting parameters between trials but also by dynamic adjustments
      during an ongoing decision.

PMID- 17229110
TI  - Modulation of singing-related activity in the songbird ventral tegmental area by
      social context.
AB  - Successful reproduction depends critically on social interactions. To understand
      the neural mechanisms underlying such interactions, the study of courtship
      singing of songbirds has many advantages. Male zebra finches produce a similar
      song during courtship of a female and while alone. However, singing-related
      neural activity in the anterior forebrain pathway (AFP), a basal ganglia
      forebrain circuit, is markedly dependent on the social context in which singing
      occurs. Thus, the AFP should receive a signal of social context from outside the
      song system. Here, we have begun to investigate the neural source of such a
      signal by recording from neurons in the ventral tegmental area (VTA), which
      provides dopaminergic input to Area X, a striatal nucleus of the AFP. The level
      of activity of most VTA neurons we recorded (32/35) was clearly modulated during
      singing, especially when males sang to a female bird. Modulation of the level of
      activity could occur in the presence of a female without singing, but typically
      was further increased when males sang to the female. In addition, activity of
      some neurons was patterned in relation to song elements, and appeared related to
      motor output. These results suggest that VTA activity could carry signals related
      to motivational aspects of singing, as well as more primary sensory and motor
      signals.

PMID- 17229112
TI  - Antimicrobial efficacy of ozonated water, gaseous ozone, sodium hypochlorite and
      chlorhexidine in infected human root canals.
AB  - AIM: To determine the antimicrobial efficacy of ozonated water, gaseous ozone,
      sodium hypochlorite and chlorhexidine in human root canals infected by
      Enterococcus faecalis. METHODOLOGY: Thirty human maxillary anterior teeth were
      prepared and inoculated with E. faecalis for 60 days. Eppendorf tubes were
      connected to the coronal portion of the teeth. Urethane hoses were attached to
      the tubes and to the entrance of a peristaltic pump. The exit of the apparatus
      corresponded to the apical portion of the root canals. The test irrigating
      solutions were ozonated water, gaseous ozone, 2.5% sodium hypochlorite (NaOCl),
      2% chlorhexidine that circulated at a constant flow of 50 mL min(-1) for 20 min.
      Samples from the root canals were collected and immersed in 7 mL Letheen Broth
      (LB), followed by incubation at 37 degrees C for 48 h. Bacterial growth was
      analysed by turbidity of the culture medium and subculture on a specific nutrient
      broth. A 0.1 mL inoculum obtained from LB was transferred to 7 mL of brain heart
      infusion and incubated at 37 degrees C for 48 h. Bacterial growth was checked by
      turbidity of the culture medium carried out in triplicate. RESULTS: No solution
      used as an irrigant over a 20-min contact time demonstrated an antimicrobial
      effect against E. faecalis. CONCLUSION: The irrigation of infected human root
      canals with ozonated water, 2.5% NaOCl, 2% chlorhexidine and the application of
      gaseous ozone for 20 min was not sufficient to inactivate E. faecalis.

PMID- 17229113
TI  - Hemin nutritional stress inhibits bacterial invasion of radicular dentine by two
      endodontic anaerobes.
AB  - AIM: To determine if anaerobic bacteria routinely found in infected dentine and
      root canals require the presence of heme in the environment in order for them to
      invade dentinal tubules. METHODOLOGY: Noncarious, unrestored human teeth with
      single root canals were prepared for invasion experiments and soaked in either
      TSB-M supplemented with hemin (5 microg mL(-1)) (n = 12 roots), TSB-M media (n =
      12 roots) or TSB-M media followed by hemin soak (n = 12 roots) for 2 days, then
      inoculated with either Prevotella intermedia ATCC 25611 or Peptostreptococcus
      micros ATCC 33270 and incubated anaerobically for 14 days. Roots were prepared
      for light microscopy, stained with Brown and Brenn or antisera raised to the
      bacteria, and invasion within tubules assessed using a tubule invasion index
      (TI). Data were analysed using Student's t-test and Mann-Whitney U-test. RESULTS:
      Prevotella intermedia (TI = 0.7 +/- 0.04) and P. micros (TI = 0.96 +/- 0.08)
      showed low invasion when grown in the presence of hemin with cells generally
      restricted to the superficial 20 microm of the tubules, whilst neither bacteria
      invaded tubules (TI = 0) when hemin was absent from the growth media (P < 0.01).
      CONCLUSIONS: Hemin was required in the growth medium for P. intermedia and P.
      micros to invade dentinal tubules.

PMID- 17229115
TI  - Substance P receptor expression in healthy and inflamed human pulp tissue.
AB  - AIM: To use radioreceptor analysis for comparing substance P (SP) receptor
      expression in human pulp tissue samples collected from teeth having a clinical
      diagnosis of acute irreversible pulpitis, healthy pulps and teeth with induced
      inflammation. METHODOLOGY: Five pulp samples were obtained from teeth having a
      clinical diagnosis of acute irreversible pulpitis. Another 10 pulp samples were
      obtained from healthy premolars where extraction was indicated for orthodontic
      purposes. In five of these premolars inflammation was induced prior to pulp
      collection. All of the samples were processed and labelled with 125I-SP. Binding
      sites were identified by 125I-SP and standard SP competition assays. Kruskal
      Wallis and Mann-Whitney (post-hoc) tests were used to establish statistically
      significant differences between the groups. RESULTS: Substance P receptor
      expression was found in all human pulp tissue samples. Most receptors were found
      in the group of pulps from teeth having a clinical diagnosis of acute
      irreversible pulpitis, followed by the group of pulps having induced
      inflammation. The least number of receptors was expressed in the group of healthy
      pulps. Statistical analysis revealed significant differences between the group of
      healthy pulp and both inflamed pulp groups (P < 0.01). CONCLUSION: Substance P
      receptor expression in human pulp tissue is significantly increased during
      inflammatory phenomena such as acute irreversible pulpitis.

PMID- 17229114
TI  - Effect of placement of calcium sulphate when used for the repair of furcation
      perforations on the seal produced by a resin-based material.
AB  - AIM: To evaluate the sealing ability of calcium sulphate when used under
      composite resin for the repair of furcation perforations having different
      diameters. METHODOLOGY: Perforations of different diameter were created in the
      floors of pulp chambers in 60 extracted human molar teeth with either a number 3
      (1 mm diameter) or 5 (1.5 mm diameter) round bur. The specimens of each group
      were divided into four sub-groups which were repaired with composite resin either
      alone or in combination with calcium sulphate that created an artificial floor
      (15 teeth group(-1)). Eight teeth without furcation perforations served as
      negative controls. In the leakage detection device, 1 mol L(-1) glucose solution
      was forced under a pressure of 1.5 KPa from the crown towards the pulp chamber
      floor. The concentration of leaked glucose was measured at 1, 2, 4, 7, 10, 15 and
      20 days using a glucose oxidase method and the data evaluated using the rank sum
      test. RESULTS: The specimens with larger perforations repaired with composite
      resin alone had significantly more leakage (P < 0.05). Using calcium sulphate as
      an artificial floor significantly decreased leakage of smaller perforations (P <
      0.05). In groups repaired with calcium sulphate under composite resin, leakage in
      smaller perforations was markedly lower than that in larger ones (P < 0.05). No
      significant difference was found between the specimens with 1 or 1.5 mm
      perforations repaired with resin alone (P > 0.05). CONCLUSIONS: Calcium sulphate
      significantly improved the sealing ability of 1 mm perforations repaired with
      composite resin but not for 1.5 mm perforations.

PMID- 17229116
TI  - Bactericidal efficacy of Er,Cr:YSGG laser irradiation against Enterococcus
      faecalis compared with NaOCl irrigation: an ex vivo pilot study.
AB  - AIM: To compare the efficacy of a standard NaOCl irrigation procedure with that
      of Er,Cr:YSGG laser irradiation in contaminated root canals having small and
      large apical foramina. METHODOLOGY: Forty root canals of extracted central
      incisor teeth with straight roots were chosen so that their apical foramina just
      permitted the tip of a size 20-K file to pass through. The canals were then
      enlarged with files to size 60 and randomly divided into four groups of 10 teeth
      each. The apical foramina of one group were widened further so that the tip of a
      size 45-K file could just pass through. After sterilization, all roots were
      inoculated with Enterococcus faecalis for 48 h at 37 degrees C. The first group
      was used as a control, the second group was irrigated with 3% NaOCl solution for
      15 min, and the last two groups having different sizes of apical foramina were
      irradiated with the Er,Cr:YSGG laser at output power from 0.5 W, with 20% air and
      water levels. The disinfecting efficacy of the groups was tested by collecting
      dentine chips from the inner canal walls of the specimens and counting viable E.
      faecalis on Mueller-Hinton agar plates. RESULTS: The differences in the mean
      number of viable colonies between the control and laser groups were statistically
      significant (P < 0.05). The control specimens had the highest number of
      microorganisms (153 x 10(3) +/- 39 x 10(3)). Complete sterilization was achieved
      in the 3% NaOCl group. The mean colony forming units (CFU) values obtained after
      Er,Cr:YSGG laser irradiation were 6.6 x 10(3) CFU and 6.5 x 10(3) CFU in root
      canals having large and small apical foramina respectively. CONCLUSION: In teeth
      with straight roots the Er,Cr:YSGG laser reduced the viable microbial population
      in root canals with small and large apical foramina but did not eradicate all
      bacteria. Three percent NaOCl inhibited the growth of E. faecalis and effectively
      sterilized all root canals.

PMID- 17229117
TI  - Sensitivity of oral bacteria to 254 nm ultraviolet light.
AB  - AIM: To explore the sensitivity of bacteria commonly found in root canals to 254
      nm ultraviolet (UV) light, either as individual cells or as participants of a
      bacterial multilayer. METHODOLOGY: The sensitivity of oral bacteria, as
      individual cells, to UV light was tested by subjecting plates streaked with
      bacteria to 254 nm UV, at a fluence of 1-20 mJ cm(-2). An experimental model was
      designed to produce a bacterial multilayer and to study absorption of UV light by
      bacteria in an outer layer and its effect on the elimination of bacteria in the
      inner layer. RESULTS: Direct exposure to relatively low doses of UV light (2-7 mJ
      cm(-2)) effectively eliminated all bacterial strains tested. Furthermore, an
      Enterococcus faecalis strain, partially resistant to a 24 h exposure to calcium
      hydroxide, was effectively eliminated within several seconds of exposure to UV
      light (P < 0.001). UV was absorbed by a multilayer of bacteria. When 4 bacterial
      cells microm(-2) were present in the light path, the UV light dose had to be
      increased by a factor of x10 to achieve 100% elimination of the bacteria in an
      inner layer. CONCLUSIONS: The application of UV light to eliminate endodontic
      pathogens may be possible. Nevertheless, its absorbance by outer layers of
      bacteria should be considered and the UV light dose adapted accordingly.

PMID- 17229118
TI  - Elevated expression of Cu, Zn-SOD and Mn-SOD mRNA in inflamed dental pulp tissue.
AB  - AIM: To determine the mRNA expression levels of copper-zinc superoxide dismutase
      (Cu, Zn-SOD) and manganese SOD (Mn-SOD) in healthy and inflamed human dental pulp
      tissue. METHODOLOGY: Sixteen patients with symptomatic irreversible pulpitis
      (eight females and eight males) were selected for study. Normal healthy pulps
      were removed from extracted mandibular third molar teeth from 10 systemically
      healthy individuals (six females and four males). QRT-PCR analysis of Cu, Zn-SOD
      and Mn-SOD mRNA expression was carried out in 16 cases of irreversible pulpitis
      and in 10 cases of systemically healthy donors. The Shapiro-Wilk's test was used
      to test the normality of data, whereas the Mann-Whitney U-test was used to
      evaluate the significance of the differences between groups. Differences in the
      expression levels were considered to be statistically significant for P-values
      <0.05. RESULTS: A significant increase (P < 0.05) occurred in both Cu, Zn-SOD and
      Mn-SOD mRNA expression in cases of irreversible pulpitis. The increase in Mn-SOD
      level was significantly higher (P < 0.05) than the change observed for Cu, Zn
      SOD. CONCLUSIONS: The development of pulpitis is associated with elevated
      transcription of both Cu, Zn-SOD and Mn-SOD; pulp tissue inflammation generated
      higher Mn-SOD transcription compared with Cu, Zn-SOD.

PMID- 17229119
TI  - In vivo comparison of working length determination with two electronic apex
      locators.
AB  - AIM: To compare the accuracy of two electronic apex locators (EALs) in the same
      teeth in vivo. METHODOLOGY: The working lengths in 20 teeth with a single canal
      were determined with two different EALs (Root ZX; J. Morita Corporation, Tokyo,
      Japan and Raypex 5 VDW, Munich, Germany) before extraction. When the first EAL
      was used the files were advanced until the display indicated the 'apical
      constriction'. The files were then fixed in removable and replaceable light
      curing composite patterns. The procedure was repeated in the same tooth with the
      second EAL and a different file. The teeth were then extracted and the apical 4
      mm of the root canals were exposed. After that the apical parts with the
      repositioned files in the canals were digitally photographed under a light
      microscope. On the images the minor diameter and the major foramen of each sample
      were marked and the respective distances of the file tips from these positions
      were measured with a computer program. Subsequently the values of the two groups
      of EALs were compared using a paired sample t-test. RESULTS: The minor foramen
      was located within the limits of +/-0.5 mm in 75% of the cases with the Root ZX
      and in 80% of the cases with Raypex 5. The paired sample t-test showed no
      significant difference between the EALs regarding determination of the minor
      foramen. CONCLUSION: The use of EALs is a reliable method for determining working
      length. The differences between the two EALs were not statistically significant.

PMID- 17229120
TI  - Cross-sectional evaluation of the periapical status and quality of root canal
      treatment in a selected population of urban Turkish adults.
AB  - AIM: To investigate the prevalence of apical periodontitis and the quality of
      root canal treatment in an adult Turkish population who visited a university
      dental clinic. SUMMARY: The periapical status of 8863 teeth belonging to 375
      patients was evaluated by two pre-calibrated observers from panoramic
      radiographs. The presence of apical periodontitis, and the prevalence and quality
      of root fillings were recorded. The relationship between the radiographic quality
      of root fillings and apical periodontitis was examined by chi-squared statistical
      analysis. Of 8863 teeth, 470 (5.3%) had undergone root canal treatment. Forty
      seven per cent of all the subjects had at least one root-filled tooth. Periapical
      radiolucencies were visible on 4.2% of teeth examined, with 53.5% of root-filled
      teeth presenting apical periodontitis. Ninety-one per cent of root-filled teeth
      with periapical pathosis were determined to have inadequate root fillings. A
      statistically significant correlation was found between the quality of root
      fillings and the presence of apical periodontitis (P < 0.05). KEY LEARNING
      POINTS: The radiographic quality of root fillings correlated with periapical
      radiographic signs of pathosis in a selected population of Turkish adults. There
      is a need to improve the standards of root canal treatment in the study
      population.

PMID- 17229121
TI  - Calcium hydroxide barrier over the apical root-end of a type III dens invaginatus
      after endodontic and surgical treatment.
AB  - AIM: To report the simultaneous endodontic and surgical treatment of a tooth
      associated with Oehlers type III dens invaginatus and a persistent periapical
      lesion, which comprised root-end resection, root-end filling and application of a
      calcium hydroxide barrier placed on the resected dentine surface. SUMMARY: Three
      root canals were identified in a tooth with a type III dens invaginatus, which
      presented with a necrotic pulp, wide foraminal opening and extensive periapical
      lesion, and with a previous history of acute abscess, intracanal exudate and
      fistula. After root canal preparation followed by intracanal application of
      calcium hydroxide pastes, the clinical-pathological status persisted. After
      periapical curettage and root-end resection, the root canals were filled,
      followed by root-end filling with Sealer 26 mixed with zinc oxide powder to a
      clay-like consistency. Calcium hydroxide paste was then applied over the exposed
      dentinal surface forming a covering over the root apex. At the 20-month follow-up
      examination the patient had no symptoms and no fistula; advanced periapical bone
      repair was obvious on the radiograph. KEY LEARNING POINTS: Because of the
      variable morphology and extent of invagination, type III dens invaginatus
      represents a challenge for conventional treatment, often leading to the need for
      a surgical approach. Sealer 26 thickened with zinc oxide powder provided
      satisfactory clinical properties for use as a root-end filling material.
      Application of a calcium hydroxide barrier over the resected root-end is a
      potential treatment option to encourage tissue repair.

PMID- 17229122
TI  - Abstracts of the 17th ASCIA Annual Scientific Meeeting, 7-10 September 2006,
      Sydney, Australia.

PMID- 17229140
TI  - Abstracts of the 7th European Congress on Epileptology, Helsinki, Finland, 2-6
      July 2006.

PMID- 17229141
TI  - Regulation of output from the plant circadian clock.
AB  - Plants, like many other organisms, have endogenous biological clocks that enable
      them to organize their physiological, metabolic and developmental processes so
      that they occur at optimal times. The best studied of these biological clocks are
      the circadian systems that regulate daily (approximately 24 h) rhythms. At the
      core of the circadian system in every organism are oscillators responsible for
      generating circadian rhythms. These oscillators can be entrained (set) by cues
      from the environment, such as daily changes in light and temperature. Completing
      the circadian clock model are the output pathways that provide a link between the
      oscillator and the various biological processes whose rhythms it controls. Over
      the past few years there has been a tremendous increase in our understanding of
      the mechanisms of the oscillator and entrainment pathways in plants and many
      useful reviews on the subject. In this review we focus on the output pathways by
      which the oscillator regulates rhythmic plant processes. In the first part of the
      review we describe the role of the circadian system in regulation at all stages
      of a plant's development, from germination and growth to reproductive development
      as well as in multiple cellular processes. Indeed, the importance of a circadian
      clock for plants can be gauged by the fact that so many facets of plant
      development are under its control. In the second part of the review we describe
      what is known about the mechanisms by which the circadian system regulates these
      output processes.

PMID- 17229142
TI  - Effect of oculopharyngeal muscular dystrophy-associated extension of seven
      alanines on the fibrillation properties of the N-terminal domain of PABPN1.
AB  - Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disease that
      usually manifests itself within the fifth decade. The most prominent symptoms are
      progressive ptosis, dysphagia, and proximal limb muscle weakness. The disorder is
      caused by trinucleotide (GCG) expansions in the N-terminal part of the poly(A)
      binding protein 1 (PABPN1) that result in the extension of a 10-alanine segment
      by up to seven more alanines. In patients, biopsy material displays intranuclear
      inclusions consisting primarily of PABPN1. Poly l-alanine-dependent fibril
      formation was studied using the recombinant N-terminal domain of PABPN1. In the
      case of the protein fragment with the expanded poly l-alanine sequence [N
      (+7)Ala], fibril formation could be induced by low amounts of fragmented fibrils
      serving as seeds. Besides homologous seeds, seeds derived from fibrils of the
      wild-type fragment (N-WT) also accelerated fibril formation of N-(+7)Ala in a
      concentration-dependent manner. Seed-induced fibrillation of N-WT was
      considerably slower than that of N-(+7)Ala. Using atomic force microscopy,
      differences in fibril morphologies between N-WT and N-(+7)Ala were detected.
      Furthermore, fibrils of N-WT showed a lower resistance against solubilization
      with the chaotropic agent guanidinium thiocyanate than those from N-(+7)Ala. Our
      data clearly reveal biophysical differences between fibrils of the two variants
      that are likely caused by divergent fibril structures.

PMID- 17229143
TI  - An investigation of the substrate specificity of the xyloglucanase Cel74A from
      Hypocrea jecorina.
AB  - The substrate specificity of the xyloglucanase Cel74A from Hypocrea jecorina
      (Trichoderma reesei) was examined using several polysaccharides and
      oligosaccharides. Our results revealed that xyloglucan chains are hydrolyzed at
      substituted Glc residues, in contrast to the action of all known xyloglucan
      endoglucanases (EC 3.2.1.151). The building block of xyloglucan, XXXG (where X is
      a substituted Glc residue, and G is an unsubstituted Glc residue), was rapidly
      degraded to XX and XG (k(cat) = 7.2 s(-1) and Km = 120 microM at 37 degrees C and
      pH 5), which has only been observed before with the oligoxyloglucan-reducing-end
      specific cellobiohydrolase from Geotrichum (EC 3.2.1.150). However, the
      cellobiohydrolase can only release XG from XXXGXXXG, whereas Cel74A hydrolyzed
      this substrate at both chain ends, resulting in XGXX. Differences in the length
      of a specific loop at subsite + 2 are discussed as being the basis for the
      divergent specificity of these xyloglucanases.

PMID- 17229144
TI  - Inhibition of pneumococcal choline-binding proteins and cell growth by esters of
      bicyclic amines.
AB  - Streptococcus pneumoniae is one of the major pathogens worldwide. The use of
      currently available antibiotics to treat pneumococcal diseases is hampered by
      increasing resistance levels; also, capsular polysaccharide-based vaccination is
      of limited efficacy. Therefore, it is desirable to find targets for the
      development of new antimicrobial drugs specifically designed to fight
      pneumococcal infections. Choline-binding proteins are a family of polypeptides,
      found in all S. pneumoniae strains, that take part in important physiologic
      processes of this bacterium. Among them are several murein hydrolases whose
      enzymatic activity is usually inhibited by an excess of choline. Using a simple
      chromatographic procedure, we have identified several choline analogs able to
      strongly interact with the choline-binding module (C-LytA) of the major autolysin
      of S. pneumoniae. Two of these compounds (atropine and ipratropium) display a
      higher binding affinity to C-LytA than choline, and also increase the stability
      of the protein. CD and fluorescence spectroscopy analyses revealed that the
      conformational changes of C-LytA upon binding of these alkaloids are different to
      those induced by choline, suggesting a different mode of binding. In vitro
      inhibition assays of three pneumococcal, choline-dependent cell wall lytic
      enzymes also demonstrated a greater inhibitory efficiency of those molecules.
      Moreover, atropine and ipratropium strongly inhibited in vitro pneumococcal
      growth, altering cell morphology and reducing cell viability, a very different
      response than that observed upon addition of an excess of choline. These results
      may open up the possibility of the development of bicyclic amines as new
      antimicrobials for use against pneumococcal pathologies.

PMID- 17229145
TI  - Histidine-rich glycoprotein exerts antibacterial activity.
AB  - Histidine-rich glycoprotein (HRGP), an abundant heparin-binding protein found in
      plasma and thrombocytes, exerts antibacterial effects against Gram-positive
      bacteria (Enterococcus faecalis and Staphylococcus aureus) and Gram-negative
      bacteria (Escherichia coli and Pseudomonas aeruginosa). Fluorescence studies and
      electron microscopy to assess membrane permeation showed that HRGP induces lysis
      of E. faecalisbacteria in the presence of Zn2+ or at low pH. Heparin blocked
      binding of the protein to E. faecalis and abolished antibacterial activity.
      Furthermore, truncated HRGP, devoid of the heparin-binding and histidine-rich
      domain, was not antibacterial. It has previously been shown that peptides
      containing consensus heparin-binding sequences (Cardin and Weintraub motifs) are
      antibacterial. Thus, the peptide (GHHPH)4, derived from the histidine-rich region
      of HRGP and containing such a heparin-binding motif, was antibacterial for E.
      faecalis in the presence of Zn2+ or at low pH. The results show a previously
      undisclosed antibacterial activity of HRGP and suggest that the histidine-rich
      and heparin-binding domain of HRGP mediates the antibacterial activity of the
      protein.

PMID- 17229146
TI  - A polyketide synthase of Plumbago indica that catalyzes the formation of
      hexaketide pyrones.
AB  - Plumbago indica L. contains naphthoquinones that are derived from six acetate
      units. To characterize the enzyme catalyzing the first step in the biosynthesis
      of these metabolites, a cDNA encoding a type III polyketide synthase (PKS) was
      isolated from roots of P. indica. The translated polypeptide shared 47-60%
      identical residues with PKSs from other plant species. Recombinant P. indica PKS
      expressed in Escherichia coli accepted acetyl-CoA as starter and carried out five
      decarboxylative condensations with malonyl coenzyme A (-CoA). The resulting
      hexaketide was not folded into a naphthalene derivative. Instead, an alpha
      pyrone, 6-(2',4'-dihydroxy-6'-methylphenyl)-4-hydroxy-2-pyrone, was produced. In
      addition, formation of alpha-pyrones with linear keto side chains derived from
      three to six acetate units was observed. As phenylpyrones could not be detected
      in P. indica roots, we propose that the novel PKS is involved in the biosynthesis
      of naphthoquinones, and additional cofactors are probably required for the
      biosynthesis of these secondary metabolites in vivo.

PMID- 17229147
TI  - Fowlicidin-3 is an alpha-helical cationic host defense peptide with potent
      antibacterial and lipopolysaccharide-neutralizing activities.
AB  - Cathelicidins are an important family of cationic host defense peptides in
      vertebrates with both antimicrobial and immunomodulatory activities. Fowlicidin-1
      and fowlicidin-2 are two newly identified chicken cathelicidins with potent
      antibacterial activities. Here we report structural and functional
      characterization of the putatively mature form of the third chicken cathelicidin,
      fowlicidin-3, for exploration of its therapeutic potential. NMR spectroscopy
      revealed that fowlicidin-3 comprises 27 amino-acid residues and adopts a
      predominantly alpha-helical structure extending from residue 9 to 25 with a
      slight kink induced by a glycine at position 17. It is highly potent against a
      broad range of Gram-negative and Gram-positive bacteria in vitro, including
      antibiotic-resistant strains, with minimum inhibitory concentrations in the range
      1-2 microM. It kills bacteria quickly, permeabilizing cytoplasmic membranes
      immediately on coming into contact with them. Unlike many other host defense
      peptides with antimicrobial activities that are diminished by serum or salt,
      fowlicidin-3 retains bacteria-killing activities in the presence of 50% serum or
      physiological concentrations of salt. Furthermore, it is capable of suppressing
      lipopolysaccharide-induced expression of proinflammatory genes in mouse
      macrophage RAW264.7 cells, with nearly complete blockage at 10 microM. Fowlicidin
      3 appears to be an excellent candidate for future development as a novel
      antimicrobial and antisepsis agent, particularly against antibiotic-resistant
      pathogens.

PMID- 17229148
TI  - Purification, microsequencing and cloning of spinach ATP-dependent
      phosphofructokinase link sequence and function for the plant enzyme.
AB  - Despite its importance in plant metabolism, no sequences of higher plant ATP
      dependent phosphofructokinase (EC 2.7.1.11) are annotated in the databases. We
      have purified the enzyme from spinach leaves 309-fold to electrophoretic
      homogeneity. The purified enzyme was a homotetramer of approximately 52 kDa
      subunits with a specific activity of 600 mU x mg(-1) and a Km value for ATP of 81
      microm. The purified enzyme was not activated by phosphate, but slightly
      inhibited instead, suggesting that it was the chloroplast isoform. The inclusion
      of adenosine 5'-(beta,gamma-imido)triphosphate was conducive to enzyme activity
      during the purification protocol. The sequences of eight tryptic peptides from
      the final protein preparation, which did not utilize pyrophosphate as a
      phosphoryl donor, were determined and an exactly corresponding cDNA was cloned.
      The sequence of enzymatically active spinach ATP-dependent phosphofructokinase
      suggests that a large family of genomics-derived higher plant sequences currently
      annotated in the databases as putative pyrophosphate-dependent
      phosphofructokinases according to sequence similarity is misannotated with
      respect to the cosubstrate.

PMID- 17229149
TI  - cGMP transport by vesicles from human and mouse erythrocytes.
AB  - cGMP secretion from cells can be mediated by ATP-binding cassette (ABC)
      transporters ABCC4, ABCC5, and ABCC11. Indirect evidence suggests that ABCC4 and
      ABCC5 contribute to cGMP transport by erythrocytes. We have re-investigated the
      issue using erythrocytes from wild-type and transporter knockout mice. Murine
      wild-type erythrocyte vesicles transported cGMP with an apparent Km that was 100
      fold higher than their human counterparts, the apparent Vmax being similar.
      Whereas cGMP transport into human vesicles was efficiently inhibited by the ABCC4
      specific substrate prostaglandin E1, cGMP transport into mouse vesicles was
      inhibited equally by Abcg2 and Abcc4 inhibitors/substrates. Similarly, cGMP
      transport into vesicles from Abcc4-/- and Abcg2-/- mice was 42% and 51% of that
      into wild-type mouse vesicles, respectively, whereas cGMP transport into vesicles
      from Abcc4(-/-)/Abcg2(-/-) mice was near background. The knockout mice were used
      to show that Abcg2-mediated cGMP transport occurred with lower affinity but
      higher Vmax than Abcc4-mediated transport. Involvement of Abcg2 in cGMP transport
      by Abcc4-/- erythrocyte vesicles was supported by higher transport at pH 5.5 than
      at pH 7.4, a characteristic of Abcg2-mediated transport. The relative
      contribution of ABCC4/Abcc4 and ABCG2/Abcg2 in cGMP transport was confirmed with
      a new inhibitor of ABCC4 transport, the protease inhibitor 4-(2
      aminoethyl)benzenesulfonyl fluoride.

PMID- 17229151
TI  - Authentic interdomain communication in an RNA helicase reconstituted by expressed
      protein ligation of two helicase domains.
AB  - RNA helicases mediate structural rearrangements of RNA or RNA-protein complexes
      at the expense of ATP hydrolysis. Members of the DEAD box helicase family consist
      of two flexibly connected helicase domains. They share nine conserved sequence
      motifs that are involved in nucleotide binding and hydrolysis, RNA binding, and
      helicase activity. Most of these motifs line the cleft between the two helicase
      domains, and extensive communication between them is required for RNA unwinding.
      The two helicase domains of the Bacillus subtilis RNA helicase YxiN were produced
      separately as intein fusions, and a functional RNA helicase was generated by
      expressed protein ligation. The ligated helicase binds adenine nucleotides with
      very similar affinities to the wild-type protein. Importantly, its intrinsically
      low ATPase activity is stimulated by RNA, and the Michaelis-Menten parameters are
      similar to those of the wild-type. Finally, ligated YxiN unwinds a minimal RNA
      substrate to an extent comparable to that of the wild-type helicase, confirming
      authentic interdomain communication.

PMID- 17229150
TI  - Purification and characterization of the cysteine proteinases in the latex of
      Vasconcellea spp.
AB  - Latex of all Vasconcellea species analyzed to date exhibits higher proteolytic
      amidase activities, generally attributed to cysteine proteinases, than the latex
      of Carica papaya. In the present study, we show that this higher activity is
      correlated with a higher concentration of enzymes in the latex of Vasconcellea
      fruits, but in addition also results from the presence of other cysteine
      proteinases or isoforms. In contrast to the cysteine proteinases present in
      papaya latex, which have been extensively studied, very little is known about the
      cysteine proteinases of Vasconcellea spp. In this investigation, several cDNA
      sequences coding for cysteine proteinases in Vasconcellea x heilbornii and
      Vasconcellea stipulata were determined using primers based on conserved
      sequences. In silico translation showed that they hold the characteristic
      features of all known papain-class cysteine proteinases, and a phylogenetic
      analysis revealed the existence of several papain and chymopapain homologues in
      these species. Ion-exchange chromatography and gel filtration procedures were
      applied on latex of V. x heilbornii in order to characterize its cysteine
      proteinases at the protein level. Five major protein fractions (VXH-I-VXH-V)
      revealing very high amidase activities (between 7.5 and 23.3 nkat x mg protein(
      1)) were isolated. After further purification, three of them were N-terminally
      sequenced. The observed microheterogeneity in the N-terminal and cDNA sequences
      reveals the presence of several distinct cysteine proteinase isoforms in the
      latex of Vasconcellea spp.

PMID- 17229152
TI  - Stimulation of fibroblast proliferation by neokyotorphin requires Ca influx and
      activation of PKA, CaMK II and MAPK/ERK.
AB  - Neokyotorphin [TSKYR, hemoglobin alpha-chain fragment (137-141)] has previously
      been shown to enhance fibroblast proliferation, its effect depending on cell
      density and serum level. Here we show the dependence of the effect of
      neokyotorphin on cell type and its correlation with the effect of protein kinase
      A (PKA) activator 8-Br-cAMP, but not the PKC activator 4beta-phorbol 12
      myristate, 13-acetate (PMA). In L929 fibroblasts, the proliferative effect of
      neokyotorphin was suppressed by the Ca2+ L-type channel inhibitors verapamil or
      nifedipine, the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane
      N,N,N',N'-tetraacetic acid acetoxymethyl ester, kinase inhibitors H-89 (PKA), KN
      62 (Ca2+/calmodulin-dependent kinase II) and PD98059 (mitogen-activated protein
      kinase). The proliferative effect of 8-Br-cAMP was also suppressed by KN-62 and
      PD98059. PKC suppression (downregulation with PMA or inhibition with
      bisindolylmaleimide XI) did not affect neokyotorphin action. The results obtained
      point to a cAMP-like action for neokyotorphin.

PMID- 17229153
TI  - All-trans-retinoic acid inhibits collapsin response mediator protein-2
      transcriptional activity during SH-SY5Y neuroblastoma cell differentiation.
AB  - Neurons are highly polarized cells composed of two structurally and functionally
      distinct parts, the axon and the dendrite. The establishment of this asymmetric
      structure is a tightly regulated process. In fact, alterations in the proteins
      involved in the configuration of the microtubule lattice are frequent in neuro
      oncologic diseases. One of these cytoplasmic mediators is the protein known as
      collapsin response mediator protein-2, which interacts with and promotes tubulin
      polymerization. In this study, we investigated collapsin response mediator
      protein-2 transcriptional regulation during all-trans-retinoic acid-induced
      differentiation of SH-SY5Y neuroblastoma cells. All-trans-retinoic acid is
      considered to be a potential preventive and therapeutic agent, and has been
      extensively used to differentiate neuroblastoma cells in vitro. Therefore, we
      first demonstrated that collapsin response mediator protein-2 mRNA levels are
      downregulated during the differentiation process. After completion of deletion
      construct analysis and mutagenesis and mobility shift assays, we concluded that
      collapsin response mediator protein-2 basal promoter activity is regulated by the
      transcription factors AP-2 and Pax-3, whereas E2F, Sp1 and NeuroD1 seem not to
      participate in its regulation. Furthermore, we finally established that reduced
      expression of collapsin response mediator protein-2 after all-trans-retinoic acid
      exposure is associated with impaired Pax-3 and AP-2 binding to their consensus
      sequences in the collapsin response mediator protein-2 promoter. Decreased
      attachment of AP-2 is a consequence of its accumulation in the cytoplasm. On the
      other hand, Pax-3 shows lower binding due to all-trans-retinoic acid-mediated
      transcriptional repression. Unraveling the molecular mechanisms behind the action
      of all-trans-retinoic acid on neuroblastoma cells may well offer new perspectives
      for its clinical application.

PMID- 17229154
TI  - Alpha 1,3-fucosyltransferase-VII regulates the signaling molecules of the insulin
      receptor pathway.
AB  - Two H7721 human hepatocarcinoma cell lines showing moderate and high expression
      of alpha1,3-fucosyltransferase (FucT)-VII cDNA were established and designated
      FucTVII-M and FucTVII-H, respectively. In alpha1,3-FucT-VII-transfected cells,
      expression of insulin receptor (InR) alpha- and beta subunits and epidermal
      growth factor receptor (EGFR) on the cell surface and in cells, as well as the
      sialyl Lewis X (SLe(x), the product of alpha1,3-FucT-VII) content of the EGFR
      were unchanged. However the level of SLe(x) on the InR alpha subunit (InR-alpha)
      was increased dramatically. Tyrosine autophosphorylation of InR-beta , but not
      EGFR, was elevated. Concomitantly, tyrosine phosphorylation of insulin receptor
      substrate-1 (IRS-1), Ser/Thr phosphorylation of protein kinase B (PKB; Akt),
      p42/44 mitogen-activated protein kinase (MAPK), MAPK kinase (MEK), and the
      protein of some other signaling molecules, such as phosphoinositide-dependent
      kinase-1 (PDK-1), novel protein kinase (PKN), c-Raf-1 and beta-catenin were also
      upregulated. The activities of PKB and transcription factor TCF were
      concomitantly stimulated. Upregulation of InR signaling molecules and their
      phosphorylation was correlated with the level of SLe(x) on InR-alpha and alpha1,3
      FucT-VII expression in cells. In addition, the phosphorylation intensity and
      difference in phosphorylation intensity between cells with different levels of
      alpha1,3-FucT-VII expression were attenuated significantly by the inhibitor of
      InR tyrosine kinase and by the mAb to SLe(x). Furthermore, insulin-induced
      signaling was facilitated in alpha1,3-FucT-VII-transfected cells, particularly
      FucTVII-H. These findings provide strong evidence that alpha1,3-FucT-VII may
      affect insulin signaling by upregulating the phosphorylation and expression of
      some signaling molecules involved in the InR-signaling pathway. These effects are
      likely mediated by its product, SLe(x), on the glycans of the InR. This is the
      first study to report that changes in the terminal structure of glycans on a
      surface receptor can modify cell signaling.

PMID- 17229155
TI  - The equinatoxin N-terminus is transferred across planar lipid membranes and helps
      to stabilize the transmembrane pore.
AB  - Equinatoxin II is a cytolytic protein isolated from the sea anemone Actinia
      equina. It is a member of the actinoporins, a family of eukaryotic pore-forming
      toxins with a unique mechanism of pore formation. Equinatoxin II is a 20 kDa
      cysteineless protein, with sphingomyelin-dependent activity. Recent studies
      showed that the N-terminal region of the molecule requires conformational
      flexibility during pore formation. An understanding of the N-terminal position in
      the final pore and its role in membrane insertion and pore stability is essential
      to define the precise molecular mechanism of pore formation. The formation of
      pores and their electrophysiologic characteristics were studied with planar lipid
      membranes. We show that amino acids at positions 1 and 3 of equinatoxin II are
      exposed to the lumen of the pore. Moreover, sulfhydryl reagents and a hexa
      histidine tag attached to the N-terminus revealed that the N-terminus of the
      toxin extends through the pore to the other (trans) side of the membrane and that
      negatively charged residues inside the pore are crucial to define the
      electrophysiologic characteristics of the channel. Finally, we detected a new,
      less stable, state with a lower conductance by using a deletion mutant in which
      the first five N-terminal amino acids were removed. We propose that the first
      five amino acids help to anchor the amphipathic helix on the trans side of the
      membrane and consequently stabilize the final transmembrane pore.

PMID- 17229156
TI  - Reductive nitrosylation and peroxynitrite-mediated oxidation of heme-hemopexin.
AB  - Hemopexin (HPX), which serves as a scavenger and transporter of toxic plasma
      heme, has been postulated to play a key role in the homeostasis of NO. In fact,
      HPX-heme(II) reversibly binds NO and facilitates NO scavenging by O(2). HPX-heme
      is formed by two four-bladed beta-propeller domains. The heme is bound between
      the two beta-propeller domains, residues His213 and His266 coordinate the heme
      iron atom. HPX-heme displays structural features of heme-proteins endowed with
      (pseudo-)enzymatic activities. In this study, the kinetics of rabbit HPX
      heme(III) reductive nitrosylation and peroxynitrite-mediated oxidation of HPX
      heme(II)-NO are reported. In the presence of excess NO, HPX-heme(III) is
      converted to HPX-heme(II)-NO by reductive nitrosylation. The second-order rate
      constant for HPX-heme(III) reductive nitrosylation is (1.3 +/- 0.1) x 10(1) m(
      1).s(-1), at pH 7.0 and 10.0 degrees C. NO binding to HPX-heme(III) is rate
      limiting. In the absence and presence of CO2 (1.2 x 10(-3) m), excess
      peroxynitrite reacts with HPX-heme(II)-NO (2.6 x 10(-6) m) leading to HPX
      heme(III) and NO, via the transient HPX-heme(III)-NO species. Values of the
      second-order rate constant for HPX-heme(III)-NO formation are (8.6 +/- 0.8) x
      10(4) and (1.2 +/- 0.2) x 10(6) m(-1).s(-1) in the absence and presence of CO2,
      respectively, at pH 7.0 and 10.0 degrees C. The CO2-independent value of the
      first-order rate constant for HPX-heme(III)-NO denitrosylation is (4.3 +/- 0.4) x
      10(-1) s(-1), at pH 7.0 and 10.0 degrees C. HPX-heme(III)-NO denitrosylation is
      rate limiting. HPX-heme(II)-NO appears to act as an efficient scavenger of
      peroxynitrite and of strong oxidants and nitrating species following the reaction
      of peroxynitrite with CO2 (e.g. ONOOC(O)O-, CO3-, and NO2).

PMID- 17229157
TI  - Crystal structures of CbiL, a methyltransferase involved in anaerobic vitamin B
      biosynthesis, and CbiL in complex with S-adenosylhomocysteine--implications for
      the reaction mechanism.
AB  - During anaerobic cobalamin (vitamin B12) biosynthesis, CbiL catalyzes methylation
      at the C-20 position of a cyclic tetrapyrrole ring using S-adenosylmethionine as
      a methyl group source. This methylation is a key modification for the ring
      contraction process, by which a porphyrin-type tetrapyrrole ring is converted to
      a corrin ring through elimination of the modified C-20 and direct bonding of C-1
      to C-19. We have determined the crystal structures of Chlorobium tepidum CbiL and
      CbiL in complex with S-adenosylhomocysteine (the S-demethyl form of S
      adenosylmethionine). CbiL forms a dimer in the crystal, and each subunit consists
      of N-terminal and C-terminal domains. S-Adenosylhomocysteine binds to a cleft
      between the two domains, where it is specifically recognized by extensive
      hydrogen bonding and van der Waals interactions. The orientation of the cobalt
      factor II substrate was modeled by simulation, and the predicted model suggests
      that the hydroxy group of Tyr226 is located in close proximity to the C-20 atom
      as well as the C-1 and C-19 atoms of the tetrapyrrole ring. These configurations
      allow us to propose a catalytic mechanism: the conserved Tyr226 residue in CbiL
      catalyzes the direct transfer of a methyl group from S-adenosylmethionine to the
      substrate through an S(N)2-like mechanism. Furthermore, the structural model of
      CbiL binding to its substrate suggests the axial residue coordinated to the
      central cobalt of cobalt-factor II.

PMID- 17229158
TI  - Global update on the use of hormonal therapy for the management of high-risk
      prostate cancer: introduction.

PMID- 17229159
TI  - Global update on defining and treating high-risk localized prostate cancer with
      leuprorelin: a European perspective.
AB  - High-risk prostate cancer can be defined as a cancer that, although clinically
      localized, will not be cured by monotherapy, whether surgery or radiation, and as
      a result will require some form of multimodal therapy, which will normally
      include luteinizing hormone-releasing hormone agonists. High-risk localized
      prostate cancer can be identified at three specific points during the management
      of the patient; before starting treatment (based on the profile of some
      predictive criteria, e.g. pathological features, prostate-specific antigen, PSA,
      level, and PSA velocity), on pathological evaluation of a surgical specimen taken
      during radical prostatectomy, or at the point of PSA relapse after radiotherapy
      or surgical therapy. Within Europe, therapeutic choice in patients identified as
      high-risk is normally made based on their age and life-expectancy. In those with
      a relatively long life-expectancy (>10 years) androgen suppression therapy (AST)
      should form part of a multimodal approach to treatment, but neoadjuvant hormonal
      therapy should be limited to use in combined hormonal therapy/radiotherapy
      protocols. AST can also be used to treat patients with PSA relapse. Several
      studies investigated the relative advantages of giving AST continuously vs
      intermittent therapy, but there are no notable differences between these
      approaches. AST monotherapy can be indicated in those patients with a shorter
      life-expectancy (<10 years), particularly if there are poor risk factors, e.g. a
      high PSA level (>50 ng/mL) or a short PSA doubling time (<12 months).

PMID- 17229160
TI  - Global update on defining and treating high-risk localized prostate cancer with
      leuprorelin: an Asian perspective.
AB  - Data from the Japanese Urological Society showed that, in Japan, almost half of
      patients with localized prostate cancer are treated with hormone therapy (HT),
      regardless of disease stage, and that radiation therapy (RT) is also widely used
      to treat high-risk patients. A retrospective study was undertaken in Japan to
      evaluate the potential benefits of using primary HT in locally advanced prostate
      cancer. Of 628 patients in the study, 63.5% were treated with combined androgen
      blockade (CAB; luteinizing hormone-releasing hormone agonists plus an
      antiandrogen) and 36.5% with medical or surgical castration. CAB treatment was
      significantly better than hormone monotherapy for disease-specific survival. The
      results also showed that, even if a patient is classified as 'high-risk', a good
      prognosis could normally be predicted based on certain variables: if their
      initial prostate-specific antigen (PSA) level was < or = 20 ng/mL, their Gleason
      score was < or = 6, and their nadir PSA decreased to < or = 0.2 ng/mL within 6
      months of HT. In this subgroup of 'good responders', any treatment, be it
      prostatectomy, RT or CAB, is likely to be effective. However, in 'poor
      responders', combined therapies with CAB and high-dose rate brachytherapy are
      likely to be needed for a clinical response. While HT is effective, it might be
      associated with a reduction in the patient's quality of life (QoL) due to adverse
      effects, e.g. a reduction in sexual function. Results from the analysis of QoL
      questionnaires completed by men of different ages with prostate cancer found that
      only sexual function, and not other QoL variables, in men aged 50-59 years
      appeared to be reduced in men who had HT, compared to age-matched controls.

PMID- 17229161
TI  - Global update on defining and treating high-risk localized prostate cancer with
      leuprorelin: a Japanese perspective--the effect of primary androgen deprivation
      therapy on stage C prostate cancer.
AB  - Stage C prostate cancer, where the tumour has extended beyond the capsule of the
      prostate, is typically a high-risk disease. According to the National Cancer
      Institute Physician Data Query the treatments of choice for stage C disease
      comprise external beam radiation therapy (with or without the addition of
      adjuvant hormone therapy), androgen deprivation by either surgery or hormone
      therapy, radical prostatectomy, or careful observation. From 2001, the Japanese
      Urological Association initiated computer-based registration of all patients with
      prostate cancer in Japan. Data show that overall, 57% of all patients and 46% of
      those with T1c to T3 disease had primary androgen deprivation therapy (PADT).
      Similarly, the Japanese Prostate Cancer Group undertook a large-scale
      epidemiological surveillance study in Japan and found that the most commonly used
      hormone therapy is PADT, regardless of disease stage. To date, two randomized,
      controlled trials of the effect of PADT on stage C prostate cancer in elderly (>
      or =75 years old) patients have been undertaken in Japan. The results showed that
      patients with locally advanced prostate cancer treated with PADT are likely to
      have a life-expectancy similar to that of the normal population. In one study,
      combined androgen blockade (CAB) with leuprorelin plus chlormadinone appeared to
      prolong time to disease progression when compared with leuprorelin monotherapy,
      but there was no difference in survival between these treatment groups. In a
      second study CAB with an luteinizing hormone-releasing hormone (LHRH) agonist
      plus bicalutamide was found to prolong time to progression when compared with
      LHRH agonist monotherapy, but survival results for these regimens are still
      awaited.

PMID- 17229164
TI  - The current status of intermittent androgen deprivation (IAD) therapy for
      prostate cancer: putting IAD under the spotlight.
AB  - Intermittent androgen deprivation (IAD) is one approach to hormonal therapy for
      prostate cancer that has been developed with the aim of minimizing the negative
      effects of therapy while maximizing the clinical benefits and the patient's
      quality of life (QoL). It can be used in any clinical situation where continuous
      AD (CAD) treatment could be applied. IAD is a cyclic therapy consisting of on
      treatment periods followed by observation periods, known as off-treatment periods
      or intervals (OTIs), and the response to therapy, or occurrence of disease
      progression, is monitored by measuring the patient's prostate-specific antigen
      (PSA) levels. The on-treatment period is generally fixed, normally lasting for 6
      9 months or in some protocols until a PSA nadir of <4 ng/mL is reached. By
      contrast, the OTI is variable and treatment is re-instituted depending on the
      patient's PSA level; however, the exact trigger point is chosen empirically. The
      potential advantages of IAD over CAD therapy are an improved QoL, a prolonged
      period of androgen dependence, a reduced incidence of the side-effects normally
      associated with AD therapy, and a decrease in the cost of care. Results from
      phase II clinical studies of IAD have shown that it has good acceptance and
      feasibility. QoL improves during the OTIs, there is reduced toxicity, and a
      positive affect on bone density compared with CAD therapy. In these studies IAD
      appeared to have no negative effects on time to progression or survival. Further
      investigations of IAD are ongoing in randomized, controlled, phase III trials in
      the USA, Canada and Europe. Most of these studies are not yet mature and final
      results are awaited; however, interim analyses from some studies suggest IAD and
      CAD therapy are equally effective in terms of progression-free survival.

PMID- 17229162
TI  - Global update on defining and treating high-risk localized prostate cancer with
      leuprorelin: a USA perspective--identifying men at diagnosis who are at high risk
      of prostate cancer death after surgery or radiation therapy.
AB  - Prostate-specific antigen doubling time (PSA-DT) after surgery or radiotherapy
      (RT) is known to be a predictive factor for death from prostate cancer (prostate
      cancer-specific mortality, PCSM). An analysis of two multi-institutional
      databases, including 8669 men with prostate cancer treated with surgery or RT,
      found that a PSA-DT of <3 months, and the specific value of the PSA-DT when > or
      = 3 months, appeared to be surrogate endpoints for PCSM after surgery or RT.
      While many PSA failures occur after local therapy for localized prostate cancer,
      few of these patients go on to die from their disease, so it is important to
      identify other factors associated with PCSM, so that the subgroup of high-risk
      patients can be identified. An analysis was undertaken to determine whether
      patients at risk of PCSM could be identified using information available at
      diagnosis. The results showed that risk factors for PCSM were a PSA velocity of
      >2.0 ng/mL/year, a Gleason score of 8-10 and an increasing PSA level. However,
      the most important risk factor that had an impact on both PCSM and all-cause
      mortality was a PSA velocity of >2.0 ng/mL/year. PSA kinetics are being
      increasingly used in the setting of rising PSA levels after radical prostatectomy
      or RT, and several studies showed that the rate of increase in PSA level at the
      time of recurrence is closely associated with time to cancer death. A PSA-DT of
      <3 months is associated with a poor prognosis, and represents 15-20% of PSA
      failures in the general population and 6-7% of PSA failures in a screened
      population, such as those included in clinical trials. Better risk-assessment
      models are needed to help to identify at an early stage men who are at high risk
      of prostate cancer death and those who are at low risk, so that each subgroup can
      receive the most appropriate therapy for their disease.

PMID- 17229166
TI  - Contemporary use of hormonal therapy in prostate cancer: managing complications
      and addressing quality-of-life issues.
AB  - While both short- and long-term androgen deprivation therapy (ADT) are effective
      for treating prostate cancer, with the clinical benefits patients can often have
      significant side-effects. It is important that these complications are recognized
      and managed appropriately so that adverse effects on the patient's quality of
      life (QoL) are minimized. The incidence of deaths from prostate cancer has
      decreased over the last decade, probably as a result of various factors including
      improved screening and diagnosis, improved treatments, and better risk assessment
      to help guide therapy. A meta-analysis of prostate cancer trials comparing the
      use of early vs late hormonal therapy found that 10-year overall survival
      increased by up to 20% between 1990 and 2000, and this was attributed to the
      earlier use of hormone therapy (HT) in these patients. Data from the USA Cancer
      of the Prostate Strategic Urological Research Endeavor database also suggest a
      significant decrease in risk in the last two decades in the USA, with more
      patients being identified with low-risk disease at diagnosis. In addition, there
      has been an increase in recent years in the use of HT at all stages of prostate
      cancer. The extensive use of ADT has raised concerns about potential adverse
      effects. ADT might be associated with a range of adverse effects that vary in
      their degree of morbidity and effect on the patient's QoL. They include hot
      flashes, osteoporosis, loss of libido or impotence, and psychological effects,
      e.g. depression, memory difficulties or emotional lability. Effective strategies
      are available for managing the major side-effects of HT, but to many patients
      these unwanted effects are often less important than the benefits of treatment.
      An investigation of health-related QoL found that men with prostate cancer
      receiving ADT had a poorer QoL than those not receiving ADT, but the difference
      was less pronounced after controlling for comorbidities. Many new therapies are
      currently under investigation which aim to maximize the clinical effects of ADT
      while reducing the adverse effects.

PMID- 17229169
TI  - The politics of life, sex and the family--rediscovering priorities for 2007.

PMID- 17229170
TI  - How to lose a billion pounds.

PMID- 17229171
TI  - Statin utilisation--recognising the role of the invisible hand.

PMID- 17229172
TI  - Stroke risk stratification in atrial fibrillation: something to EXAMINE more
      closely.

PMID- 17229173
TI  - Management of atrial fibrillation: the NICE guidelines.

PMID- 17229174
TI  - The diagnosis of premature ejaculation.

PMID- 17229175
TI  - Preventing adverse drug reactions.

PMID- 17229176
TI  - Evaluation of the cost savings and clinical outcomes of switching patients from
      atorvastatin to simvastatin and losartan to candesartan in a Primary Care
      setting.
AB  - This study was carried out in a Primary Care practice in the UK to assess the
      clinical and practical implications, cost savings and patients' perspective of
      switching to generic drugs. In the 70 patients switched from atorvastatin to
      simvastatin there was no significant change in mean total cholesterol 4 months
      after the switch (4.07 +/- 0.55 mmol/L prior to the switch and 4.10 +/- 0.73
      mmol/L post-switch) and only one patient switched back because of side effects.
      One hundred and fifteen patients were switched from losartan to candesartan.
      Seven switched back but in those that remained on candesartan there was a small,
      significant (p = 0.0006), reduction in blood pressure after the switch
      (138.9/78.7 +/- 13.2/7.0 to 136.3/76.1 +/- 14.7/8.4 mmHg). No adverse events
      attributable to the switch were reported in either group and the net annualised
      savings for the year 2005-2006 were 12,715.58 pounds for the statin and 13,374.40
      pounds for the antihypertensive switch, respectively.

PMID- 17229177
TI  - Antithrombotic drug prescription in atrial fibrillation and its rationale among
      general practitioners, internists and cardiologists in The Netherlands--The
      EXAMINE-AF study. A questionnaire survey.
AB  - The objective of the EXAMINE-AF study was to record and compare antithrombotic
      treatment in patients with atrial fibrillation (AF) in daily clinical practice of
      general practitioners, internists and cardiologists in the Netherlands. Eighty
      six general practitioners, 93 internists and 99 cardiologists responded to postal
      questionnaires and enrolled 1596 patients: 365, 351 and 880 respectively. A
      cardiologist was indicated to be the main treating physician for AF in 82% of all
      patients; current antithrombotic treatment was initiated in 80% by a
      cardiologist. Of all patients, 84% were at high risk for stroke and therefore
      were eligible for oral anticoagulation treatment, but only 64% actually received
      this. Cardiologists instituted appropriate antithrombotic treatment best,
      compared with general practitioners and internists (70% vs. 58% and 55%; p <
      0.001). Positive predictive factors for oral anticoagulation prescription were
      previous stroke/transient ischaemic attack (OR, 2.31; 95% CI, 1.33-4.02) and
      heart failure (OR, 1.72; 95% CI, 1.23-2.42). Contraindications for oral
      anticoagulation (OR, 0.46; 95% CI, 0.32-0.68), treatment by a general
      practitioner (OR, 0.29; 95% CI, 0.20-0.42) or internist (OR, 0.24; 95% CI, 0.15
      0.39) were important factors for withholding treatment. Antithrombotic treatment
      in AF patients is well instituted in primary and secondary care in the
      Netherlands. Cardiologists play a key role in the diagnosis and management of the
      majority of AF patients, even in those regularly attending other physicians.
      Factors for oral anticoagulation prescription are heart failure, physician
      specialty and contraindications. Availability of guidelines seems instrumental
      for application of appropriate antithrombotic treatment.

PMID- 17229178
TI  - Features of metabolic syndrome in non-diabetic Italians and Brazilians: a
      discriminant analysis.
AB  - This aim of this study was to compare the characteristics of metabolic syndrome
      (MetS) in a Brazilian and an Italian population. The subjects were non-diabetic
      men and women aged 40-74 years from population-based surveys: 1242 from Brazil
      and 1198 from Italy. Logistic regression models were used to compare adjusted
      prevalence rates and make a discrimination analysis to distinguish the subjects
      with a diagnosis of MetS in the two groups. Dyslipidemia [low high-density
      lipoprotein (HDL)-cholesterol] and impaired fasting glucose were more prevalent
      among the Brazilians, and increased blood pressure and abdominal obesity (in men)
      among the Italians. Generally, the Italians showed higher prevalence of overall
      obesity and high pulse-pressure, and the Brazilians had higher prevalence of
      metabolic markers of insulin resistance. Among the subjects with the syndrome,
      HDL-cholesterol was the most discriminant factor, followed by plasma uric acid
      levels (which were higher in the Brazilians). The Italian men had a larger waist
      circumference and the Italian women higher body mass index values than the
      Brazilians. Italians had higher systolic and lower diastolic pressure values. The
      patterns of the metabolic alterations seemed to be more linked to insulin
      resistance among Brazilian subjects, whereas obesity seemed to play a more
      important role among the Italians. Although they are not sufficient to support
      the hypothesis of differences in the underlying pathophysiological processes
      between these groups, our results illustrate the difficulty of using a single
      unifying definition of MetS, and suggest that different benefits may be obtained
      from treatments targeting obesity, blood pressure or insulin resistance.

PMID- 17229179
TI  - Lack of management of cardiovascular risk factors in type 2 diabetic patients.
AB  - Effective management of diabetic patients includes comprehensive control for not
      only blood sugar, but also other cardiovascular risk factors. We assessed whether
      haemoglobin A1c (A1C) concentrations, blood pressure, low density lipoprotein
      (LDL) cholesterol levels and microalbuminuria were regularly measured in 281
      patients with type 2 diabetes who received care for over 1 year in the Department
      of Family Medicine located in an urban area of Korea. Subsequently, in patients
      with A1C > 7%; blood pressure >130/80 mmHg; LDL cholesterol levels >100 mg/dl; or
      microalbuminuria, we evaluated the status of management for those cardiovascular
      risk factors. Physicians were most likely to measure A1C levels (98.6%), but less
      likely to measure microalbuminuria (56.2%), LDL cholesterol (73.7%), or blood
      pressure (74.4%). Patients whose A1C levels were above the goal (78.2%) were
      likely to receive optimal therapy. In contrast, only 21.1% of patients with
      uncontrolled blood pressure and 5.3% of patients with LDL cholesterol levels
      above the target range received optimal management. Of the 36 patients with
      microalbuminuria or overt proteinuria, 66.7% took angiotensin-converting enzyme
      inhibitors or angiotensin receptor blockers. Measurement of parameters indicating
      cardiovascular risk factors in type 2 diabetic patients was not optimal,
      particularly regular measurements for microalbuminuria and for controlling LDL
      cholesterol and blood pressure. These findings indicate a need for greater
      education of comprehensive cardiovascular management in type 2 diabetic patients
      and their physicians.

PMID- 17229180
TI  - Acute renal infarction: a 10-year experience.
AB  - The diagnosis of acute renal infarction (ARI) is often delayed or unrecognised
      because of its non-specific presentation and the rarity of the disease. We
      evaluated the clinical presentations, laboratory findings, underlying medical
      conditions and treatment of 18 Chinese patients with ARI who presented to the
      emergency department (ED) of a tertiary teaching hospital from 1995 to 2004. We
      identified 14 non-trauma and four trauma patients with ARI. The mean duration
      from the onset of symptoms to the diagnosis of ARI was 1.9 days. The prevalence
      of concurrent events was 39%. About 64.5% of non-trauma patients had histories of
      atrial fibrillation, structural heart diseases or previous embolic events. The
      laboratory characteristics were neither specific nor sensitive for the diagnosis
      of ARI. Conservative treatment, local intra-arterial thrombolytic and i.v.
      thrombolytic therapies were provided in nine, five and two patients respectively.
      Decreased effective renal plasma flow in affected kidneys was found in three of
      three patients. Serum creatinine (Cr) was normal or elevated not more than 25% of
      baseline in 16 cases. ARI may resemble many non-renal diseases; however, repeated
      evaluation and a high index of suspicion are required for early diagnosis.
      Concurrent injuries or thromboembolism in other foci should be noticed. Early
      contrast-enhanced computerized tomography scan should be considered for high-risk
      patients. Patients with ARI should be followed by functional studies rather than
      serum Cr level.

PMID- 17229181
TI  - The aetiology of premature ejaculation and the mind-body problem: implications
      for practice.
AB  - Recent attempts to find effective pharmacological treatments for premature
      ejaculation (PE) have spurred significant interest in the causes of, consequences
      of, and existing therapies for this common male sexual dysfunction. The recurring
      tendency in science and medicine, however, to dichotomise causes of such problems
      into either biological or psychological is not only counterproductive, it is
      misguided. Ejaculatory response should be viewed as a system of integrated and
      inseparable hardwired and softwired central and peripheral responses, some being
      readily modifiable, others not. Such a view argues that treatment of PE aimed at
      multiple levels of functioning will be self-enhancing and ultimately more
      effective in producing positive therapeutic outcomes than strategies relying
      solely on either psychological or biological approaches.

PMID- 17229182
TI  - Role of postprandial hyperglycaemia in cardiovascular disease in diabetes.
AB  - Diabetes is associated with a marked increase in the risk of atherosclerotic
      vascular disorders, including coronary, cerebrovascular and peripheral artery
      disease. Cardiovascular disease (CVD) could account for disabilities and high
      mortality rates in patients with diabetes. Conventional risk factors, including
      hyperlipidaemia, hypertension, smoking, obesity, lack of exercise and a positive
      family history, contribute similarly to macrovascular complications in type 2
      diabetic patients and non-diabetic subjects. The levels of these factors in
      diabetic patients are certainly increased, but not enough to explain the
      exaggerated risk for macrovascular complications in diabetic population.
      Therefore, specific diabetes-related risk factors should be involved in the
      excess risk in diabetic patients. In this paper, we review the molecular
      mechanisms for accelerated atherosclerosis in diabetes, especially focusing on
      postprandial hyperglycaemia. We also discuss here the potential therapeutic
      strategy that specifically targets CVD in patients with diabetes.

PMID- 17229183
TI  - Diabetic macular oedema: a clinical overview.
AB  - Diabetic retinopathy is the leading cause of blindness in working aged-adults in
      westernised countries. Diabetic macular oedema (DMO) is a manifestation of
      diabetic retinopathy and is the leading cause of the visual impairment that
      occurs with diabetic retinopathy. There are multiple ways of classifying DMO;
      however, none appear to be wholly satisfactory. DMO occurs more frequently in
      type 2 diabetes mellitus, and appears to be more prevalent as the duration of
      diabetes increases, and as the severity of diabetic retinopathy worsens. There
      are multiple risk factors in common with diabetic retinopathy, such as
      hyperglycaemia, hypertension and dyslipidaemia; however, specific factors such as
      the presence of renal disease appear to be more significantly associated with
      DMO. Whereas the gold standard for diagnosis of DMO is via clinical examination,
      there is considerable variability involved, and hence, this has led to the advent
      of more objective methods of quantifying the degree of retinal thickness, such as
      optical coherence tomography. Laser photocoagulation appears to be the only
      universally acceptable treatment of choice to date; however, this is a
      destructive therapy, and its side effects coupled with the suboptimal efficacy
      has led to the advent of potential new therapies which will undoubtedly
      compliment the existing approaches, in the future management of a patient with
      DMO.

PMID- 17229184
TI  - Diagnosis and treatment of obsessive-compulsive disorder and related disorders.
AB  - Obsessive-compulsive disorder (OCD) is currently recognised as one of the most
      common psychiatric disorders as well as one of the most disabling of all medical
      disorders. Obsessive-compulsive related disorders (OCRDs), often comorbid with
      OCD, include many distinct psychiatric conditions (i.e. some somatoform
      disorders, eating disorders, impulse control disorders and some neurological
      conditions) which have overlapping symptoms and compulsive qualities with OCD.
      Although effective treatments exist, OCD and related disorders are often
      underdiagnosed and undertreated. Serotonin reuptake inhibitors (SRIs) and
      cognitive behavioural therapy (CBT) represent the first-line treatment for OCD
      and related disorders. However, the time and the doses of the medications used in
      the treatment of OCD and related disorders differ from those recommended in
      depressive disorders. In addition, remission is not common for patients with OCD
      and related disorders in clinical practice, and poor responders as well as
      refractory cases may benefit from different treatment strategies including
      integrated treatment, pharmacological augmentation and brain stimulation
      techniques.

PMID- 17229185
TI  - Non-nucleoside reverse transcriptase inhibitors: a review.
AB  - Non-nucleoside reverse transcriptase inhibitors form the backbone of
      antiretroviral treatment for many HIV-infected individuals. The tolerability,
      pill burden and efficacy associated with this class of agents make them a
      frequent choice for first-line therapy. Here we review nevirapine and efavirenz
      in terms of efficacy, resistance and toxicity, focusing particularly on the use
      of nevirapine to prevent mother-to-child transmission in developing countries.

PMID- 17229186
TI  - Management of advanced HIV disease with no other complications in women and in
      Africans.
AB  - The number of patients who present with advanced human immunodeficiency virus
      (HIV) disease [defined as a helper lymphocyte (CD4) count <50 cells/mm3 or the
      presence of an acquired immunodeficiency syndrome (AIDS)-defining illness] is
      increasing. In the USA during 1994-1999, a relatively stable proportion of 43% of
      people diagnosed with HIV infection were tested late in the infection (had AIDS
      diagnosed within 1 year of diagnosis). A recent review of newly diagnosed
      infections in 2003 found that 301/977 (31%) of patients in the UK and Ireland
      presented late (<200 CD4 cells/mm3). Before a diagnosis is made, patients with
      advanced disease do not benefit from antiretroviral therapy and may continue to
      transmit the infection to others. Furthermore, when antiretroviral therapy is
      initiated in patients with CD4 counts of 201-350 cells/mm(3), the risk of death
      is lower than when treatment is started at lower CD4 cell counts. With the
      increasing prevalence of HIV in women and African immigrants, some doctors are
      concerned that different management approaches need to be used in these groups.
      This article reviews the evidence and some clinical scenarios for patients with
      advanced disease without complications and women and Africans who may present
      with advanced HIV disease. The aim is to offer practical advice on therapeutic
      options for treatment-naive patients who present with advanced HIV disease on the
      basis of available clinical evidence.

PMID- 17229187
TI  - 'Idiopathic' pericarditis--the clinician's challenge [nothing is idiopathic].
AB  - Reports on the aetiologic distribution of acute pericarditis vary significantly
      from study to study. We attempted to summarise reports on incidence of different
      aetiologies of pericarditis and explain the variable range of reported
      frequencies of different aetiologies. The literature between 1978 and 2005 was
      reviewed for comparative incidence of acute pericarditis. Reports of more than 50
      subjects were included. The most common cause of pericarditis was 'idiopathic'
      pericarditis (mean: 26.1%), followed by neoplastic diseases (mean: 25.6%) and
      iatrogenic pericarditis (mean: 16.3%). Each mean had a wide range of 95%
      confidence interval. In summary, the clinician is confronted by a huge dispersion
      of reported frequencies of pericarditis aetiologies as a consequence of multiple
      factors. Recognising specific rare causes of pericarditis, often essential for
      early diagnosis and successful treatment, means coping with that aetiologic
      dispersion and its implied probabilities.

PMID- 17229188
TI  - Effect of sitaxsentan treatment on quality of life in pulmonary arterial
      hypertension.
AB  - In recent years new therapeutic options have been developed for the management of
      pulmonary arterial hypertension (PAH). Sitaxsentan is an oral, once daily, highly
      selective endothelin A receptor antagonist that recently demonstrated a positive
      effect on functional capacity and haemodynamics of PAH patients. The aim of this
      study is to evaluate the effect of sitaxsentan in the quality of life (QOL) of
      PAH patients. Twenty-three patients with idiopathic PAH or PAH associated to
      collagen vascular diseases were evaluated at baseline and after 16 weeks of
      treatment with sitaxsentan 100 mg orally, once daily. 6-min walk test distance
      (6MWD) and QOL questionnaire (QOLQ) (SF-36) were obtained at baseline and at week
      16. There was a significant improvement in functional capacity evaluated by 6MWD
      (472 m vs. 490 m, p = 0.03) and also in the physical component of the QOLQ (p <
      0.01). Evaluating each of the domains of the SF-36 QOLQ, those more related to
      physical capacity presented a significant increase while the domains related to
      the mental component presented a trend of improvement, without reaching
      statistical significance. Sitaxsentan improves QOL in patients with PAH mainly
      through the domains related to functional capacity.

PMID- 17229189
TI  - Analysis of adverse drug reactions for preventability.
AB  - Although preventability criteria have been assessed for all adverse drug
      reactions (ADRs) investigated at our institution over the past 12 years, a
      systematic evaluation of the data had not been performed. This project analysed
      preventability data previously collected to identify the potential areas for
      process improvements. A 3-year retrospective analysis was performed. All ADRs
      were categorised by drug, drug class, severity, probability of causality and
      preventability. Factors involved in preventability were assessed and tallied.
      Descriptive statistics was used to analyse the data. Most ADRs occurred prior to
      admission. In the outpatient setting, anticoagulants and anticonvulsants were
      associated with more preventable ADRs (pADRs) than other drug classes, followed
      by cardiotonic agents and non-steroidal anti-inflammatory drugs (NSAIDs). For
      ADRs that occurred in hospitalised patients, antibiotics and opiates were
      associated with approximately half of all pADRs. The preventability categories
      most frequently associated with ADRs prior to admission were presence of a toxic
      drug level and drug-drug interactions, while inappropriate dose, route or
      frequency was the most common preventability category for inpatient ADRs. The
      majority of pADRs were moderate in severity in both the in- and outpatient
      settings. Drugs and drug classes involved in pADRs differ in the in- and
      outpatient settings. Preventability categories also differ by setting. Most pADRs
      occur prior to admission in our healthcare system. This presents a challenge in
      terms of implementing the process changes to reduce the pADRs, as patients in the
      community are outside our control.

PMID- 17229191
TI  - Fluvastatin and cancer.

PMID- 17229190
TI  - Severe pulmonary haemorrhage accompanying hepatorenal failure in fulminant
      leptospirosis.
AB  - Leptospirosis is a re-emerging spirochetal zoonosis with a worldwide distribution
      affecting both animals and humans. The clinical syndromes may vary from a
      subclinical infection to a severe illness. Although it may potentially have a
      fulminant and fatal course, leptospirosis usually remains as an underdiagnosed
      cause of multiorgan failure. In this study, we report a patient with
      leptospirosis who presented with a fulminant course of diffuse alveolar
      haemorrhage and hepatorenal failure. His clinical condition deteriorated, despite
      appropriate antibiotic therapy and haemodialysis. However, he showed prompt
      clinical improvement when corticosteroids and plasma exchange were instituted in
      addition to the original therapy. We conclude that leptospirosis should be
      considered in any case presenting with pulmonary haemorrhage and hepatorenal
      failure. Plasma exchange and corticosteroids may be a choice of treatment in
      selected patients unresponsive to conventional therapy. Potential benefits of
      plasma exchange and corticosteroids may be based on a toxin- and/or cytokine
      mediated pathogenesis of the disease.

PMID- 17229193
TI  - Phyto- and trichobezoars as foreign bodies of the gastrointestinal tract.

PMID- 17229195
TI  - [Consensus recommendations on the use of botulinum toxin type A in aesthetic
      medicine].

PMID- 17229196
TI  - Grave acidosis after severe anaphylactic bronchospasm: friend or foe?
AB  - In a 20-year-old woman with known asthma, anaphylactic bronchospasm induced a
      grave combined respiratory and metabolic acidosis (pH(a) 6.66) with marked
      hypoxaemia (S(a)O(2) 45%). The beneficial effects of the rightward shift of the
      oxyhaemoglobin dissociation curve on tissue O(2) unloading at such pH was more
      than offset by the negative effect on S(a)O(2) at the reduced P(a)O(2) (7.0 kPa)
      found in this patient. This case illustrates the detrimental effect of grave
      acidosis on arterial blood oxygen content at subnormal P(a)O(2) values, the
      beneficial effect of a supranormal P(a)O(2) on the S(a)O(2) in such patients, and
      the rapid remission rate of life-threatening acidosis and blood lactate after
      adequate ventilation and tissue oxygenation were secured. The initial treatment
      of the patient and clinically relevant considerations are discussed.

PMID- 17229197
TI  - [Dermatological guideline efforts for 2007 in perspective].

PMID- 17229199
TI  - Treatment modalities for allergic reactions in pigmented tattoos.
AB  - Decorative tattoos have become very popular. As a result, a higher number of
      hypersensitivity reactions are seen, caused by the mostly undeclared tattoo dyes.
      If local and intralesional therapy with corticosteroids is not effective, total
      excision was formerly considered the best approach. Selective laser therapy
      offers an alternative approach for removing the offending pigment. Case reports
      are used to illustrate the individual treatment options for removal of tattoos.

PMID- 17229201
TI  - Chronic urticaria--which clinical parameters are pathogenetically relevant? A
      retrospective investigation of 339 patients.
AB  - BACKGROUND: Urticaria is a clinical reaction pattern triggered by many factors
      causing liberation of vasoactive substances such as histamine, prostaglandins and
      kinins. It presents as transient itching wheals which are either limited to the
      local stimulus area or more widespread. Urticaria is classified according to its
      duration into acute (duration > or = 6 weeks) and chronic (duration 6 weeks)
      forms. Various clinical investigations may be initiated to diagnose the cause.
      This study critically evaluates the relevance of frequently performed laboratory
      investigations and searches for infectious foci, as well as the results of
      physical provocation testing and oral provocation with food additives. PATIENTS
      AND METHODS: The laboratory and clinical data of 339 patients who had been
      treated for urticaria at the Christian-Albrechts-University in Kiel over a period
      of four years were collected in a data entry form and statistically evaluated.
      Nominal values were analyzed by their relative and absolute quantities,
      quantitative parameters with the help of statistical data such as minimum,
      maximum, median and 25th and 75th percentiles. RESULTS: Chronic recurrent
      urticaria was most common, accounting for 52% of cases. Women were affected 1.8
      times more often than men. One-third of the patients also had angioedema. The
      medians of all laboratory parameters evaluated were within normal values. Only
      rarely were elevated antinuclear antibody titers, abnormal thyroid function tests
      or active infections such as hepatitis B or borreliosis detected. The search for
      infectious foci identified tonsillitis or sinusitis in almost 50% of analyzed
      patients. Positive reactions to physical testing occurred in 30% of patients and
      in 11% to oral provocation with various food additives. CONCLUSIONS: This study
      of a large patient group stresses the relevance of individually-tailored
      evaluations in patients affected with urticaria rather than an expensive initial
      broad diagnostic testing. More specific searches should be based on individual
      clues.

PMID- 17229200
TI  - Systemic dermatological treatment with relevance for male fertility.
AB  - The dermatologist employs systemic agents with likely gametotoxic side effects,
      including cytotoxic, immunosuppressive, immunomodulatory and biological agents.
      The impact of chemotherapy on male fertility depends on the treatment protocol as
      well as the pre-treatment spermatogenesis status. Sperm concentration starts to
      drop about 2 weeks after beginning chemotherapy and reaches a maximum after 2-3
      months. About half show recovery after 12-36 months. One year after therapy is
      completed, a treated patient has no increased risk of fathering a malformed
      child. There are no reports of methotrexate patients fathering children with
      malformations, most likely because impaired fertility or embryogenesis arrest.
      Cryopreservation of male gametes should be recommended prior to cytotoxic
      treatment, since the likelihood of post-treatment fertility is unpredictable. The
      cryopreservation causes a loss of vital spermatozoa by 30-70% but does not
      influence the genetic information of gametes. Males treated with retinoids have
      no reproductive safety risk. Biologicals inhibiting TNF alpha show a positive
      effect on sperm function in vitro.

PMID- 17229202
TI  - Multiple juvenile xanthogranulomas successfully treated with CO laser.
AB  - Juvenile xanthogranulomas are a rare disease entity within the spectrum of
      cutaneous non-Langerhans cell histiocytoses characterized by single or multiple
      cutaneous xanthogranulomas without further organ involvement. A 16-year-old girl
      developed multiple xanthogranulomas in various skin regions, especially the trunk
      and the flexural areas, over a period of 6 months. The clinical diagnosis was
      confirmed by H&E histology, showing a histiocytic infiltrate admixed with foam
      cells and Touton giant cells, and by immunohistochemistry using anti-bodies to
      stabilin-1 whose expression is highly specific for cutaneous non-Langerhans cell
      histiocytoses. No diabetes insipidus, pituitary hyperplasia or paraproteinemia
      were observed. Skin lesions were treated with a CO(2) laser and did not reappear
      during a 5 years follow-up period.

PMID- 17229203
TI  - Human seminal plasma allergy--a rare cause of recurrent anaphylaxis.
AB  - Allergies to sperm are very uncommon. A 23-year old woman with atopic dermatitis
      complained of three attacks of angioedema, urticaria, wheezing and weakness. When
      questioned about factors causing exercise-induced anaphylaxis, the patient
      reported having had sexual intercourse with the same partner one hour before each
      event. When using condoms, no symptoms occurred. Human seminal plasma allergy was
      confirmed by positive skin testing with the partner's sperm. Specific IgE
      antibodies against human seminal plasma were not found. The patient received an
      emergency kit for anaphylaxis.

PMID- 17229204
TI  - Skin diseases in diabetes mellitus.

PMID- 17229205
TI  - [Persistent reddish-brown plaque on the occiput of a 62-year-old patient].

PMID- 17229206
TI  - [Tangential skin graft].

PMID- 17229207
TI  - Onychomycosis.

PMID- 17229208
TI  - Ribonucleotide reductase and the regulation of DNA replication: an old story and
      an ancient heritage.
AB  - All organisms that synthesize their own DNA have evolved mechanisms for
      maintaining a constant DNA/cell mass ratio independent of growth rate. The
      DNA/cell mass ratio is a central parameter in the processes controlling the cell
      cycle. The co-ordination of DNA replication with cell growth involves multiple
      levels of regulation. DNA synthesis is initiated at specific sites on the
      chromosome termed origins of replication, and proceeds bidirectionally to
      elongate and duplicate the chromosome. These two processes, initiation and
      elongation, therefore determine the total rate of DNA synthesis in the cell. In
      Escherichia coli, initiation depends on the DnaA protein while elongation depends
      on a multiprotein replication factory that incorporates deoxyribonucleotides
      (dNTPs) into the growing DNA chain. The enzyme ribonucleotide reductase (RNR) is
      universally responsible for synthesizing the necessary dNTPs. In this review we
      examine the role RNR plays in regulating the total rate of DNA synthesis in E.
      coli and, hence, in maintaining constant DNA/cell mass ratios during normal
      growth and under conditions of DNA stress.

PMID- 17229209
TI  - Reduced action of polypeptide release factors induces mRNA cleavage and tmRNA
      tagging at stop codons in Escherichia coli.
AB  - Certain C-terminal sequences of nascent peptide cause an efficient protein
      tagging by tmRNA system at stop codons in Escherichia coli. Here, we demonstrate
      that both mRNA cleavage and tmRNA tagging occur at UAG stop codon recognized
      specifically by polypeptide release factor 1 (RF-1) when the activity of RF-1 is
      reduced by a mutation in the prfA gene without requirement of particular C
      terminal sequences of nascent peptide. The tmRNA tagging and mRNA cleavage in the
      prfA mutant were eliminated when the wild-type RF-1 but not RF-2 was supplied
      from plasmid. In addition, depletion of either RF-1 or RF-2 induces
      endonucleolytic cleavage and tmRNA tagging at UAG or UGA stop codons
      respectively. We conclude that ribosome stalling at the cognate stop codon caused
      by reduced activity or expression of RF-1 or RF-2 is responsible for mRNA
      cleavage. The present data along with our previous studies strongly suggest that
      ribosome stalling leads to endonucleolytic cleavage of mRNA in general resulting
      in non-stop mRNA and that the 3' end of non-stop mRNA is probably only target for
      the tmRNA system.

PMID- 17229210
TI  - Maturation of the 5' end of Bacillus subtilis 16S rRNA by the essential
      ribonuclease YkqC/RNase J1.
AB  - Functional ribosomal RNAs are generated from longer precursor species in every
      organism known. Maturation of the 5' side of 16S rRNA in Escherichia coli is
      catalysed in a two-step process by the cooperative action of RNase E and RNase G.
      However, many bacteria lack RNase E and RNase G orthologues, raising the question
      as to how 16S rRNA processing occurs in these organisms. Here we show that the
      maturation of Bacillus subtilis 16S rRNA is also a two-step process and that the
      enzyme responsible for the generation of the mature 5' end is the widely
      distributed essential ribonuclease YkqC/RNase J1. Depletion of B. subtilis of
      RNase J1 results in an accumulation of 16S rRNA precursors in vivo. The precursor
      species are found in polysomes suggesting that they can function in translation.
      Mutation of the predicted catalytic site of RNase J1 abolishes both 16S rRNA
      processing and cell viability. Finally, purified RNase J1 can correctly mature
      precursor 16S rRNA assembled in 70S ribosomes, showing that its role is direct.

PMID- 17229211
TI  - Haem recognition by a Staphylococcus aureus NEAT domain.
AB  - Successful pathogenic organisms have developed mechanisms to thrive under extreme
      levels of iron restriction. Haem-iron represents the largest iron reservoir in
      the human body and is a significant source of iron for some bacterial pathogens.
      NEAT (NEAr Transporter) domains are found exclusively in a family of cell surface
      proteins in Gram-positive bacteria. Many NEAT domain-containing proteins,
      including IsdA in Staphylococcus aureus, are implicated in haem binding. Here, we
      show that overexpression of IsdA in S. aureus enhances growth and an inactivation
      mutant of IsdA has a growth defect, compared with wild type, when grown in media
      containing haem as the sole iron source. Furthermore, the haem-binding property
      of IsdA is contained within the NEAT domain. Crystal structures of the apo-IsdA
      NEAT domain and in complex with haem were solved and reveal a clathrin adapter
      like beta-sandwich fold with a large hydrophobic haem-binding pocket. Haem is
      bound with the propionate groups directed at the molecular surface and the iron
      is co-ordinated solely by Tyr(166). The phenol groups of Tyr(166) and Tyr(170)
      form an H-bond that may function in regulating haem binding and release. An
      analysis of IsdA structure-sequence alignments indicate that conservation of
      Tyr(166) is a predictor of haem binding by NEAT domains.

PMID- 17229212
TI  - A family of stage-specific alanine-rich proteins on the surface of epimastigote
      forms of Trypanosoma brucei.
AB  - A 'two coat' model of the life cycle of Trypanosoma brucei has prevailed for more
      than 15 years. Metacyclic forms transmitted by infected tsetse flies and
      mammalian bloodstream forms are covered by variant surface glycoproteins. All
      other life cycle stages were believed to have a procyclin coat, until it was
      shown recently that epimastigote forms in tsetse salivary glands express
      procyclin mRNAs without translating them. As epimastigote forms cannot be
      cultured, a procedure was devised to compare the transcriptomes of parasites in
      different fly tissues. Transcripts encoding a family of glycosylphosphatidyl
      inositol-anchored proteins, BARPs (previously called bloodstream alanine-rich
      proteins), were 20-fold more abundant in salivary gland than midgut (procyclic)
      trypanosomes. Anti-BARP antisera reacted strongly and exclusively with salivary
      gland parasites and a BARP 3' flanking region directed epimastigote-specific
      expression of reporter genes in the fly, but inhibited expression in bloodstream
      and procyclic forms. In contrast to an earlier report, we could not detect BARPs
      in bloodstream forms. We propose that BARPs form a stage-specific coat for
      epimastigote forms and suggest renaming them brucei alanine-rich proteins.

PMID- 17229213
TI  - Acid pH activation of the PmrA/PmrB two-component regulatory system of Salmonella
      enterica.
AB  - Acid pH often triggers changes in gene expression. However, little is known about
      the identity of the gene products that sense fluctuations in extracytoplasmic pH.
      The Gram-negative pathogen Salmonella enterica serovar Typhimurium experiences a
      number of acidic environments both inside and outside animal hosts. Growth in
      mild acid (pH 5.8) promotes transcription of genes activated by the response
      regulator PmrA, but the signalling pathway(s) that mediates this response has
      thus far remained unexplored. Here we report that this activation requires both
      PmrA's cognate sensor kinase PmrB, which had been previously shown to respond to
      Fe(3+) and Al(3+), and PmrA's post-translational activator PmrD. Substitution of
      a conserved histidine or of either one of four conserved glutamic acid residues
      in the periplasmic domain of PmrB severely decreased or abolished the mild acid
      promoted transcription of PmrA-activated genes. The PmrA/PmrB system controls
      lipopolysaccharide modifications mediating resistance to the antibiotic polymyxin
      B. Wild-type Salmonella grown at pH 5.8 were > 100 000-fold more resistant to
      polymyxin B than organisms grown at pH 7.7. Our results suggest that protonation
      of the PmrB periplasmic histidine and/or of the glutamic acid residues activate
      the PmrA protein, and that mild acid promotes cellular changes resulting in
      polymyxin B resistance.

PMID- 17229217
TI  - Review article: Indeterminate colitis--definition, diagnosis and management.
AB  - BACKGROUND: The term indeterminate colitis is imprecise and without a generally
      accepted definition. Nevertheless, it is a term that is commonly used by
      gastroenterologists, pathologists and surgeons. AIM: To offer an opinion
      supported by published data, about the appropriate use of the term indeterminate
      colitis by addressing a series of questions. METHODS: A PubMed database search
      was performed using the keywords, 'colitis' and 'inflammatory bowel disease' each
      combined individually with the following adjectives: 'indeterminate',
      'unclassified', 'undefined', 'undiagnosed' and 'non-specific'. RESULTS: There is
      no generally accepted definition of indeterminate colitis. All current
      applications of the term rely on exclusionary criteria and there is no
      confirmatory diagnostic test. Nevertheless, the diagnosis of indeterminate
      colitis appears to be durable in a subgroup of patients, suggesting that this
      group represents a unique phenotype. CONCLUSIONS: Indeterminate colitis has
      expanded from a strictly defined, postcolectomy pathological diagnosis to become,
      in addition, a clinical diagnosis without generally accepted criteria. A
      diagnosis of indeterminate colitis should be qualified with descriptors for the
      diagnostic criteria applied.

PMID- 17229216
TI  - Review article: Altering the natural history of Crohn's disease--evidence for and
      against current therapies.
AB  - BACKGROUND: The natural course of Crohn's disease is characterized by flare-ups
      altered with periods of remission. The majority of Crohn's disease patients need
      surgery within 10 years of diagnosis. Major advances in treatment options over
      the past years have made our treatment goals more ambitious and modification of
      the natural course has become the ultimate endpoint. AIM: To review the evidence
      of existing therapies for Crohn's disease for changing the natural history.
      METHODS: A Medline search was undertaken by using 'natural history', 'Crohn's
      disease', 'therapy' (corticosteroids, azathioprine, methotrexate, infliximab and
      enteral feeding), 'surgery', 'hospitalizations' and 'mucosal healing'. RESULTS:
      Corticosteroids do not alter the disease course and maintenance therapy with
      corticosteroids should be avoided given their side effects. The immunomodulators
      azathioprine and methotrexate heal the mucosa but their onset of action is slow.
      Infliximab therapy introduces rapid mucosal healing and is associated with
      decreased hospitalizations and surgical interventions. Despite the fact that
      immunomodulators and infliximab are effective in maintaining clinical and
      endoscopic remission, there is little hard evidence at present that these
      therapies alter the natural history of the disease. The main reason being the
      fact that these therapies have so far been used only in refractory patients and
      that early initiation in the right patient is crucial in order to change the
      disease course. CONCLUSION: Prospective studies should validate predictors of
      complicated disease and randomized studies in high-risk groups should be
      performed to answer if early introduction of immunomodulators or biological
      therapies slows down disease progression and alters natural history.

PMID- 17229218
TI  - Systematic review: Infliximab therapy in ulcerative colitis.
AB  - AIM: To perform a systematic review and meta-analysis on the efficacy and
      tolerance of infliximab in ulcerative colitis. METHODS:  SELECTION OF STUDIES:
      evaluating efficacy of infliximab in ulcerative colitis. For the meta-analysis,
      randomized clinical trials comparing infliximab vs. placebo/steroids. SEARCH
      STRATEGY: electronic and manual. Study quality: independently assessed by two
      reviewers. DATA SYNTHESIS: meta-analysis combining the odds ratios (OR). RESULTS:
      Thirty-four studies (896 patients) evaluated infliximab therapy in UC, with
      heterogeneous results. Mean short-term (2.3 weeks) response and remission with
      infliximab was 68% (95% CI 65-71%) and 40% (36-44%). Mean long-term (8.9 months)
      response and remission was 53% (49-56%) and 39% (35-42%). Five randomized double
      blind studies compared infliximab with placebo, the meta-analysis showing an
      advantage (P < 0.001) of infliximab in all endpoints (short-/long-term
      response/remission): ORs from 2.7 to 4.6, and number-needed-to-treat (NNT) from 3
      to 5. Similar infliximab response was calculated independently of the indication
      (steroid-refractory/non-steroid-refractory) or the dose (5/10 mg/kg). Adverse
      effects were reported in 83% and 75% of the infliximab and placebo-treated
      patients (OR = 1.52; 95% CI 1.03-2.24; number-needed-to-harm (NNH) was 14).
      CONCLUSION: Infliximab is more effective than placebo, with an NNT from 3 to 5,
      for the treatment of moderate-to-severe UC, achieving clinical remission in 40%
      of the patients at approximately 9 months of follow-up. Further studies are
      necessary to confirm the long-term efficacy of infliximab in ulcerative colitis.

PMID- 17229219
TI  - Systematic review: Rebound acid hypersecretion after therapy with proton pump
      inhibitors.
AB  - BACKGROUND: The occurrence and the clinical relevance of rebound acid
      hypersecretion after discontinuation of proton pump inhibitors is unclear. AIM:
      To perform a systematic review of rebound acid hypersecretion after
      discontinuation of proton pump inhibitors. METHODS: PubMed, Embase and Central
      were searched up to October 2005 with indexed terms. RESULTS: Eight studies were
      included, sample size was 6-32. The studies used both basal and stimulated acid
      output as parameters to study rebound acid hypersecretion and assessed these at
      different time points and with variable methods. Five studies (including four
      randomized studies) did not find any evidence for rebound acid hypersecretion
      after proton pump inhibitor therapy. Of the remaining three studies, the duration
      of proton pump inhibitor therapy was the longest and two of these studies were
      the only to assess Helicobacter pylori status of their study subjects. These two
      studies suggested that rebound acid hypersecretion may occur in H. pylori
      negatives after 8 weeks of proton pump inhibitors. CONCLUSIONS: Studies that have
      investigated rebound acid hypersecretion after cessation of proton pump inhibitor
      treatment are heterogenic in design, methods and outcome. There is some evidence
      from uncontrolled trials for an increased capacity to secrete acid in H. pylori
      negative subjects after 8 weeks of treatment. There is no strong evidence for a
      clinically relevant increased acid production after withdrawal of proton pump
      inhibitor therapy.

PMID- 17229220
TI  - Long-term prognosis in Crohn's disease: An epidemiological study of patients
      diagnosed more than 20 years ago in Cardiff.
AB  - AIM: To investigate the incidence of death in patients diagnosed with Crohn's
      disease in Cardiff over 20 years ago. METHODS: The Cardiff database of patients
      with Crohn's disease contains data on all patients diagnosed there since 1934.
      Patients (394) diagnosed before 1 January 1985 were traced and their mortality
      status on 31 December 2004 was established. RESULTS: The overall standardized
      mortality ratio (SMR) was 1.29 (95% CI 1.12-1.45) and it has not significantly
      changed since the 1970s. SMR decreases with age, from 16.95 (95% CI 14.99-18.91)
      for patients aged 10-19 years (although only one death) to 0.92 (95% CI 0.65
      1.19) in those over 75 years. Kaplan-Meier analysis of age at death shows that
      patients diagnosed aged 10-26 years have median age at death of 58 years, those
      aged 27-52 years of 66 years, those aged 53-58 years of 74 years, and those over
      59 years of 79 years. CONCLUSIONS: It shows a significantly raised SMR, not
      statistically changed since the 1970s and similar to other chronic conditions.
      Patients diagnosed younger have worse prognosis than those diagnosed later in
      life and a reduced life expectancy compared with the general population.

PMID- 17229221
TI  - Impact of long-term enteral nutrition on clinical and endoscopic recurrence after
      resection for Crohn's disease: A prospective, non-randomized, parallel,
      controlled study.
AB  - BACKGROUND: The impact of enteral nutrition on post-operative recurrence has not
      been properly examined. AIM: To investigate the impact of enteral nutrition using
      an elemental diet on clinical and endoscopic recurrence after resection for
      Crohn's disease. METHODS: Forty consecutive patients who underwent resection for
      ileal or ileocolonic Crohn's disease were studied. After operation, 20 patients
      continuously received enteral nutritional therapy (EN group), and 20 had neither
      nutritional therapy nor food restriction (non-EN group). In the EN group, enteral
      formula (Elental) was infused through a nasogastric tube in the night-time, and
      low fat foods were taken in the daytime. All patients were followed up regularly
      for 1 year after operation. Ileocolonoscopy was performed at 6 and 12 months
      after operation. RESULTS: One patient (5%) in the EN group and seven (35%) in the
      non-EN group developed clinical recurrence during 1-year follow-up (P = 0.048).
      Six months after operation, five patients (25%) in the EN group and eight (40%)
      in the non-EN group developed endoscopic recurrence (P = 0.50). Twelve months
      after operation, endoscopic recurrence was observed in six patients (30%) in the
      EN group and 14 (70%) in the non-EN group (P = 0.027). CONCLUSIONS: Our long-term
      enteral nutritional therapy significantly reduced clinical and endoscopic
      recurrence after resection for Crohn's disease.

PMID- 17229222
TI  - Birth outcome in women treated with azathioprine or mercaptopurine during
      pregnancy: A Danish nationwide cohort study.
AB  - BACKGROUND: Data on birth outcome after exposure to azathioprine or
      mercaptopurine during pregnancy is sparse. AIM: To examine the risk of adverse
      birth outcome among newborns of women exposed to azathioprine or mercaptopurine
      during pregnancy. METHODS: Data on drug use and births were obtained from Danish
      population registries. We included 76 exposed pregnancies in 69 women. Of these,
      we used 64 pregnancies exposed 30 days before conception or during the first
      trimester to examine the risk of congenital abnormalities, and 65 pregnancies
      exposed during the entire pregnancy to examine preterm birth and low birth weight
      at term. Their birth outcomes were compared with outcomes among women who did not
      fill prescriptions for azathioprine or mercaptopurine during pregnancy. RESULTS:
      Azathioprine- or mercaptopurine-exposed women had a higher risk of adverse birth
      outcomes than unexposed controls. However, when the comparison was limited to
      newborns of women with the same types of underlying disease, relative risks for
      spontaneous and induced preterm birth, low birth weight at term, and congenital
      abnormalities were 1.1 (95% CI: 0.5-2.4), 4.0 (95% CI: 1.5-10.8), 1.7 (95% CI:
      0.3-8.7) and 1.1 (95% CI: 0.5-2.9), respectively. CONCLUSION: Our results suggest
      that adverse birth outcomes were caused by the underlying disease rather than by
      use of azathioprine or mercaptopurine.

PMID- 17229223
TI  - Does Barrett's oesophagus develop over time in patients with chronic gastro
      oesophageal reflux disease?
AB  - BACKGROUND: Barrett's oesophagus is present in 8-10% of patients with gastro
      oesophageal reflux disease (GERD). AIM: We performed a cohort study to determine
      the incidence of Barrett's oesophagus in patients with chronic heartburn
      symptoms. METHODS: We identified patients, with GERD and/or Barrett's oesophagus
      between 1998 and 2004 by primary or secondary International Classification of
      Diseases (ICD-9) codes of 530.81 and/or 530.2, who had two or more
      oesophagogastroduodenoscopies performed at least 6 months apart. RESULTS: We
      screened 11 040 patients (41 390 random data entries by ICD-9 code) and enrolled
      515 (4.6%) GERD patients and 169 (1.5%) Barrett's oesophagus patients. The mean
      (+/-s.d.) number of oesophagogastroduodenoscopies in the GERD cohort was 3.2 +/-
      1.8 (range: 2-15) over 3.4 +/- 2.2 (range: 0.5-11) years. None of the 412 (80%)
      GERD patients with non-erosive disease developed Barrett's oesophagus over a mean
      follow-up time of 3.4 +/- 2.2 years (95% CI: 0-0.9%). Five (1%) of the 103 GERD
      patients with erosive oesophagitis developed subsequent Barrett's oesophagus.
      Fifty-seven per cent of the GERD patients were on PPI therapy at the time of
      index endoscopy. None of the 169 Barrett's oesophagus patients had normal index
      oesophagogastroduodenoscopies within a mean retrospective time period of 4.5 +/-
      2.8 years (95% CI: 0-2%). Using the ICD-9 code of 530.2 as a predictor of the
      presence of Barrett's oesophagus, the sensitivity was 79% with a specificity of
      88%. CONCLUSION: The majority of patients with GERD do not appear to develop
      Barrett's oesophagus when it is not present on the index endoscopy.

PMID- 17229224
TI  - Assessment of dietary nutrients that influence perception of intra-oesophageal
      acid reflux events in patients with gastro-oesophageal reflux disease.
AB  - BACKGROUND: Gastro-oesophageal reflux disease symptoms are most commonly reported
      postprandially, suggesting that some diet components are likely to induce
      symptoms more than others. AIMS: To determine which of the various dietary
      nutrients is a strong predictive factor for symptom generation in association
      with an acid reflux event. METHODS: Subjects with typical heartburn symptoms were
      evaluated by the gastro-oesophageal reflux disease Symptom Checklist,
      demographics questionnaire, upper endoscopy and pH testing. During the pH study,
      patients completed a detailed 24-h dietary intake record. This included time of
      meals, description of food components and the amount and type of food
      preparation. RESULTS: Fifty gastro-oesophageal reflux disease patients completed
      all stages of the study. A total of 112 (78%) symptoms were considered as sensed
      reflux event. Body mass index did not correlate with having perceived reflux.
      Patients who consumed more cholesterol, saturated fatty acids and had more
      percentage calories from fat were significantly more likely to experience a
      perceived reflux event. Regression analysis and beta-coefficient were
      specifically significant for cholesterol. CONCLUSION: Of all dietary nutrients,
      cholesterol enhances the most the perception of intra-oesophageal acid reflux
      events in patients with gastro-oesophageal reflux disease.

PMID- 17229225
TI  - Comparison of gastric pH with omeprazole magnesium 20.6 mg (Prilosec OTC) o.m.
      famotidine 10 mg (Pepcid AC) b.d. and famotidine 20 mg b.d. over 14 days of
      treatment.
AB  - BACKGROUND: The onset of acid inhibition for proton pump inhibitors is slower
      than with H2RAs and generally considered to be at a steady-state after 5 days.
      Thus, little direct comparison data exists between H2RAs and proton pump
      inhibitors for gastric acid suppression on day 1 of therapy. Furthermore, the
      durability of their acid suppression has not been systematically compared. AIM:
      To compare the effects of 20.6 mg omeprazole magnesium o.m. (Ome-Mg 20),
      famotidine 10 mg b.d. (Fam 10) and famotidine 20 mg b.d. (Fam 20) on intragastric
      pH on day 1 and throughout 14 days of dosing. METHODS: The study was a
      randomized, double-blind, three-dosing regimens, three-period crossover. Healthy
      adults with frequent heartburn (> or =2 days/week) underwent 24-h gastric pH
      monitoring on days 0 (baseline), 1, 3, 7 and 14. RESULTS: Thirty-one subjects
      were included in the per-protocol analyses. On day 1, the mean percentage time pH
      > 4 (pH4%) was higher for Ome-Mg 20, 44.6%, than for Fam 10, 36.7% (P = 0.032),
      and not different from Fam 20, 46.9% (P = 0.541). The pH4% was higher for Ome-Mg
      20 than either famotidine regimen on all subsequent monitoring days (P < 0.001).
      The 24-h area under the mean intragastric pH curve showed a similar pattern.
      Furthermore, after day 1, Ome-Mg 20 demonstrated an increasing and sustained
      effect in contrast to a decreasing effect for famotidine, consistent with H2RA
      tolerance. CONCLUSION: Gastric acid suppression on Ome-Mg 20 mg o.m. over 14 days
      was comparable with Fam 10 mg b.d. or Fam 20 mg b.d. on day 1, and superior
      thereafter.

PMID- 17229226
TI  - Skin conductance or entropy for detection of non-noxious stimulation during
      different clinical levels of sedation.
AB  - BACKGROUND: State entropy (SE) measures electroencephalographic signals, whereas
      response entropy (RE) also includes frontal electromyographic activity. In the
      presence of electromyographic activity, the RE index is larger than the SE index,
      the difference being denoted as RE-Delta (RE-Delta= RE - SE). Skin conductance
      (SC) may be expressed by a slow reacting variable, the mean SC level, the
      derivate of the mean SC level (D-SC), the number of SC fluctuations (NSCF) or the
      amplitude of the SC fluctuations (ASCF), which directly shows skin sympathetic
      nerve activity. The goal of this study was to evaluate whether these SC and
      entropy variables could differentiate between the responses obtained to load
      sound stimuli at different sedation levels before the induction of general
      anaesthesia. METHODS: Twenty women scheduled for gynaecological laparotomy were
      studied. The modified observer's assessment of alertness sedation (OAAS) was used
      to classify the patients' hypnotic levels. White sounds (98 dB) were given at
      OAAS level 5 without propofol, at OAAS levels 4-3 and 3-2 with propofol and at
      OAAS levels 3-2 and < 2 with propofol and remifentanil. RESULTS: RE and SE showed
      a steady decline from OAAS level 5 to level < 2 (P < 0.01). RE-Delta did not
      discriminate between any of the OAAS levels (P= NS). The mean SC level
      discriminated between OAAS levels 4-3 to < 2 (P < 0.01). D-SC discriminated
      between all the different OAAS levels (P < 0.01). NSCF discriminated between OAAS
      levels 5 to 3-2 (P < 0.05), but did not discriminate at OAAS level 3-2 between
      propofol alone or combined with remifentanil, or between OAAS level 3-2 and < 2.
      ASCF differentiated between OAAS levels 5 and 4 (P < 0.001) and OAAS levels 3-2
      and < 2 (P < 0.05) only. CONCLUSION: RE, SE and D-SC showed a similar
      discrimination between sound responses at the different sedation levels.

PMID- 17229227
TI  - Comparison of skin conductance with entropy during intubation, tetanic
      stimulation and emergence from general anaesthesia.
AB  - BACKGROUND: The number of skin conductance fluctuations (NSCF) expresses
      sympathetic skin nerve activity. The response entropy (RE) measures
      electromyographic and electroencephalographic activity in the forehead. The state
      entropy (SE) measures mainly electroencephalographic activity. When the
      suppression of frontal muscular activity is complete, RE is equal to SE. RE-Delta
      is defined as SE minus RE. The purposes of this study were to examine whether
      NSCF and RE-Delta correlate with signs of clinical stress during intubation and
      tetanic noxious stimulation and to elucidate how rapidly and accurately entropy
      and NSCF react during emergence from general anaesthesia. METHODS: Twenty women
      scheduled for gynaecological laparotomy were studied. During intubation in
      remifentanil and propofol general anaesthesia, NSCF and RE-Delta were correlated
      with the clinical stress score. After a wash-out period, two series of tetanic
      stimuli were given, the first with (R+) and the second without (R-) remifentanil
      infusion. The tetanic pre-stimuli periods were compared with the tetanic post
      stimuli periods, and R+ was compared with R-. During emergence, the responses of
      entropy and skin conductance were related to the time of extubation. RESULTS:
      NSCF correlated well with the clinical stress score during intubation (r(2)=
      0.73, P < 0.0005). RE-Delta showed a weaker correlation (r(2)= 0.33, P= 0.007).
      During tetanic stimuli, the NSCF pre-stimuli level was lower than the post
      stimuli level (P < 0.001), and the NSCF R+ response was lower than the NSCF R-
      response (P= 0.002). RE-Delta did not show similar differences. During emergence,
      RE reacted before NSCF and SE (P= 0.003). CONCLUSION: NSCF was better than RE
      Delta for the measurement of clinical stress during intubation, and was sensitive
      to tetanic stimuli at different opioid analgesic levels, by contrast with RE
      Delta. Both modalities were able to predict emergence at the end of anaesthesia,
      but RE was more rapid.

PMID- 17229228
TI  - Patients' willingness to pay for anti-emetic treatment.
AB  - BACKGROUND: Post-operative nausea and vomiting (PONV) is a common complication of
      anaesthesia. This study was conducted in 100 German and 100 Turkish patients
      scheduled for elective surgery under general anaesthesia to assess the amount
      patients were willing to pay for an anti-emetic that completely prevented PONV.
      METHODS: Post-operatively, using Dixon's up and down method, patients completed
      an interactive computer questionnaire with a random starting point to determine
      how much of their own money they were willing to pay for a totally effective anti
      emetic treatment. RESULTS: On average, participants were willing to pay 65 euro
      in Germany and 68 euro in Turkey to avoid PONV. However, patients who actually
      experienced PONV were willing to pay larger amounts: 96 euro in Germany and 99
      euro in Turkey. The amount patients were willing to pay was related to female
      sex, history of motion sickness, non-smoking status and better education.
      CONCLUSIONS: Despite differences in political and cultural origin, health care
      system and financial background, the amount patients were willing to pay for an
      effective anti-emetic was similar in both Germany and Turkey to that reported
      previously for the USA.

PMID- 17229230
TI  - Arterial oxygen tension increase 2-3 h after hyperbaric oxygen therapy: a
      prospective observational study.
AB  - BACKGROUND: Inhalation of hyperbaric oxygen (HBO) has been reported to decrease
      arterial oxygen tension (PaO(2)) in the early period after exposure. The current
      investigation aimed at evaluating whether and to what extent arterial blood gases
      were affected in mechanically ventilated intensive care patients within 6 h after
      HBO treatment. METHODS: Arterial blood gases were measured in 11 ventilated
      subjects [nine males, two females, synchronized intermittent mandatory
      ventilation (SIMV) mode] undergoing HBO therapy for necrotizing soft tissue
      infection (seven patients), burn injury (two patients), crush injury (one
      patient) and major abdominal surgery (one patient). Blood gases were obtained
      with the patients in the supine position under continuous analgesia and sedation
      before the hyperbaric session (baseline), during isopression, after
      decompression, after each transport, and 1, 2, 3 and 6 h after exposure. Heart
      rates and blood pressures were recorded. Intensive care unit (ICU) ventilator
      settings remained unchanged. Transport and chamber ventilator settings were
      adjusted to baseline with maintenance of tidal volumes and positive end
      expiratory pressure (PEEP) levels. The hyperbaric protocol consisted of 222.9 kPa
      (2.2 absolute atmospheres) and a 50-min isopression phase. The paired Wilcoxon's
      test was used. RESULTS: Major findings (median values, 25%/75% quartiles) as per
      cent change of baseline: PaO(2) values decreased by 19.7% (7.0/31.7, P < 0.01)
      after 1 h and were elevated over baseline by 9.3% (1.5/13.7, P < 0.05) after 3 h.
      SaO(2), alveolar-arterial oxygen tension difference and PaO(2)/FiO(2) ratio
      behaved concomitantly. Acid-base status and carbon dioxide tension were
      unaffected. CONCLUSION: Arterial oxygen tension declines transiently after HBO
      and subsequently improves over baseline in intensive care patients on volume
      controlled mechanical ventilation. The effectiveness of other ventilation modes
      or a standardized recruitment manoeuvre has yet to be evaluated.

PMID- 17229229
TI  - Control of shivering during regional anaesthesia: prophylactic ketamine and
      granisetron.
AB  - BACKGROUND: The aim of the present study was to compare placebo, ketamine,
      granisetron and a combination of ketamine and granisetron in the prevention of
      shivering caused by regional anaesthesia. METHODS: In this prospective,
      randomized, double-blind study, 160 ASA I and II patients undergoing urological
      surgery were included. Subarachnoid anaesthesia was performed in all patients
      with bupivacaine 15 mg. The patients were randomly allocated to receive saline
      (group P, n= 40), ketamine 0.5 mg (group K, n= 40), granisetron 3 mg (group G, n=
      40) or ketamine 0.25 mg + granisetron 1.5 mg (group KG, n= 40). Shivering was
      graded as 0 = no shivering, 1 = piloerection or peripheral vasoconstriction but
      no visible shivering, 2 = muscular activity in only one muscle group, 3 =
      muscular activity in more than one muscle group but not generalized, and 4 =
      shivering involving the whole body. If 15 min after spinal anaesthesia and
      concomitant administration of a prophylactic dose of one of the study drugs, the
      patients shivered according to at least grade 3, the prophylaxis was regarded as
      ineffective and intravenous (i.v.) pethidine 25 mg was administered. RESULTS:
      After 15 min, the number of patients with observed shivering was 22 in group P, 6
      in group G, 7 in group GK and 0 in group K. The difference between group K and
      all the other groups was statistically significant (P < 0.0001). The number of
      patients with a shivering score of 3 was statistically significantly higher in
      group P compared with the other groups. CONCLUSION: The prophylactic use of 0.5
      mg/kg i.v. ketamine was effective in preventing shivering developed during
      regional anaesthesia.

PMID- 17229231
TI  - Hemodynamic effect of sustained pulmonary hyperinflation in patients after
      cardiac surgery: open vs. closed chest.
AB  - BACKGROUND: In a previous study, we showed that sustained pulmonary
      hyperinflation, i.e. a lung recruitment maneuver, after closure of the chest in
      patients undergoing cardiac surgery had significantly negative effects on the
      central hemodynamics. As elevated pleural pressure is believed to be a major
      cause of this cardiovascular impairment, we hypothesized that performing the
      sustained pulmonary hyperinflation under open chest conditions would affect the
      circulation less. METHODS: Patients undergoing cardiac by-pass surgery were
      included and sustained pulmonary hyperinflations (40 cmH(2)O airway pressure for
      15 s) were performed immediately before and after closure of the sternum. Pulse
      contour cardiac output, heart rate, mean arterial pressure and pulse pressure
      variation were measured before, during and 1 min after the hyperinflations. Left
      ventricular dimensions were measured using trans-esophageal echocardiography.
      RESULTS: Cardiac output (CO) and mean arterial blood pressure (MAP) decreased
      significantly during the sustained pulmonary hyperinflation both with an open and
      closed chest (in parenthesis): CO by 50 (45)% and MAP by 19 (24)%. The left
      ventricular end-diastolic area was significantly reduced by 24 (33)%. One minute
      after the hyperinflation, all measured variables had returned to baseline values.
      No significant differences in the measured variables were found between the two
      conditions before, during or 1 min after the hyperinflation. CONCLUSION: Contrary
      to our hypothesis, sustained pulmonary hyperinflations with the chest open, i.e.
      before sternal closure, had similar negative effects on central hemodynamics as
      those performed with the chest closed, i.e. after sternal closure.

PMID- 17229234
TI  - Intraneural catheter placement for post-operative pain therapy in an amputee.

PMID- 17229236
TI  - Review article: steroid resistance in inflammatory bowel disease - mechanisms and
      therapeutic strategies.
AB  - BACKGROUND: Steroid resistance in inflammatory bowel disease presents a difficult
      clinical challenge. The advent of biological therapies coupled with an increasing
      understanding of the pathogenesis of inflammatory bowel disease has provided new
      therapeutic options. METHODS: We review the available literature of the
      mechanisms behind steroid resistance. In addition, we outline some of the options
      available for treating those patients who fail to respond adequately to
      glucocorticoids. RESULTS: Approximately 30% of patients prescribed
      glucocorticoids will not achieve clinical remission. Many such patients are
      offered immunosuppressive or, recently, biological agents. However, these agents
      are ineffective in a large proportion of patients. Immunosuppressive agents only
      bring 40-60% of patients into remission, and biological agents typically induce
      remission in just 40% of patients. In this review, the possible explanations for
      glucocorticoid resistance are discussed. Recent evidence suggests that in many
      patients it is mediated by interleukin-2. Basiliximab, a biological agent that
      interrupts interleukin-2 signalling, has shown significant benefit in early
      clinical studies. CONCLUSIONS: Patients who fail to respond to steroid therapy
      should have alternative agents introduced in a timely fashion. Steroid refractory
      inflammatory bowel disease remains a difficult condition to treat, but new
      therapies and managements are emerging.

PMID- 17229237
TI  - Systematic review: fluoroquinolones for the treatment of intra-abdominal surgical
      infections.
AB  - BACKGROUND: Intra-abdominal infections result in substantial morbidity and
      mortality. Fluoroquinolones are among the various regimens that are used for the
      treatment of these infections. AIM: To evaluate the available data from
      laboratory and clinical studies regarding the use of fluoroquinolones for the
      treatment of patients with intra-abdominal infections. METHODS: We searched for
      relevant laboratory and clinical studies in the PubMed and the Cochrane Library
      databases. RESULTS: Good pharmacokinetic and pharmacodynamic properties of
      fluoroquinolones in inflamed abdominal tissue are reported in several laboratory
      studies. In six prospective non-randomized clinical studies of patients with
      intra-abdominal infections, the clinical success achieved with the use of
      fluoroquinolones ranged from 77% to 94%. In 10 randomized-controlled trials
      fluoroquinolone-based regimens were compared with other commonly used (mainly
      beta-lactam-based) regimens. Clinical success, bacterial eradication, withdrawal
      because of toxicity and mortality were similar between the compared treatment
      arms except from two randomized-controlled trials, in which clinical success was
      statistically higher in the fluoroquinolone treatment arm. CONCLUSIONS:
      Fluoroquinolones seem to be an effective and relatively safe option for the
      treatment of patients with intra-abdominal infections.

PMID- 17229238
TI  - Systematic review: Helicobacter pylori eradication for the prevention of gastric
      cancer.
AB  - BACKGROUND: Helicobacter pylori is recognized as one of the most significant risk
      factors for gastric cancer, and H. pylori eradication has been proposed as a
      possible primary chemo-preventive strategy to reduce gastric cancer incidence.
      AIM: To evaluate the available evidence on the efficacy of H. pylori eradication
      in the prevention of gastric cancer. METHODS: Epidemiological, observational and
      interventional studies, as well as decisional models, were taken into account in
      this review. RESULTS: Large-scale epidemiological studies clearly link H. pylori
      infection with non-cardia gastric cancer. Current evidence suggests that, in a
      subpopulation of treated subjects, H. pylori eradication prevents the progression
      of preneoplastic lesions. Studies that have attempted to evaluate the effect of
      H. pylori eradication on the incidence of gastric cancer have not provided
      definitive answers. H. pylori eradication seems to reduce the incidence of
      gastric cancer in patients without baseline precancerous gastric lesions.
      Decisional models suggest that H. pylori screening could be cost-effective, but
      there is not yet sufficient evidence to support the setting up of a general
      screening programme. CONCLUSION: Helicobacter pylori eradication is a plausible
      intervention for gastric cancer prevention; however, it seems to be relevant in
      only a subset of subjects.

PMID- 17229239
TI  - Meta-analysis: the efficacy of over-the-counter gastro-oesophageal reflux disease
      therapies.
AB  - BACKGROUND: Over-the-counter histamine-2 receptor antagonists, antacids and
      alginate/antacids are commonly used for gastro-oesophageal reflux disease. AIM:
      To conduct a systematic review and meta-analysis of related treatment trials.
      METHODS: We performed a systematic search and abstraction of randomized, placebo
      controlled trials conducted during 1972-2005. Study quality was measured by the
      Jadad score (0-5). Results were pooled using random effects model. RESULTS: Ten
      trials (n = 3442, placebo = 2940; Jadad score 3.5) showed a higher response with
      histamine-2 receptor antagonists in regard to complete relief of heartburn,
      symptomatic improvement, and episodes requiring rescue antacids. The absolute
      benefit increase was 10-12% and relative benefit increase was 19-41%. Four trials
      (n = 578, placebo = 577; Jadad score 3.5) showed a trend in favour of antacids in
      symptomatic improvement (absolute benefit increase 8%, 95% CI: 0-16%; relative
      benefit increase 0.11) and requirement of rescue antacids (OR 0.70, 95% CI: 0.59
      0.84). Four trials (n = 146, placebo = 138; Jadad score 3.8) found
      alginate/antacid combination superior to placebo in symptomatic improvement
      (absolute benefit increase 26%, 95% CI: 12%-41%, relative benefit increase 0.60).
      CONCLUSIONS: Over-the-counter medications are effective in treating symptomatic
      gastro-oesophageal reflux disease. Compared with the placebo response, which
      ranged between 37% and 64%, the relative benefit increase was up to 41% with
      histamine-2 receptor antagonists, 60% with alginate/antacid combinations, and 11%
      with antacids.

PMID- 17229240
TI  - Meta-analysis: the effect of supplementation with probiotics on eradication rates
      and adverse events during Helicobacter pylori eradication therapy.
AB  - BACKGROUND: Recent evidence found probiotics could inhibit Helicobacter pylori
      colonization from both in vitro and in vivo studies. AIM: To systematically
      evaluate whether adding probiotics to anti-H. pylori regimens could improve
      eradication rates and reduce side effects during anti-H. pylori treatment.
      METHODS: Eligible articles were identified by searches of electronic databases.
      We included all randomized trials comparing probiotics supplementation to placebo
      or no treatment during anti-H. pylori regimens. Statistical analysis was
      performed with Review Manager 4.2.8. Subanalysis/Sensitivity analysis was also
      performed. RESULTS: We identified 14 randomized trials (n = 1671). Pooled H.
      pylori eradication rates were 83.6% (95% CI = 80.5-86.7%) and 74.8% (95% CI =
      71.1-78.5%) for patients with or without probiotics by intention-to-treat
      analysis, respectively, the odds ratio (OR) was 1.84 (95% CI = 1.34-2.54); the
      occurrence of total side effects were 24.7% (95% CI = 20.0-29.4%) and 38.5% (95%
      CI = 33.0-44.1%) for groups with or without probiotics, especially for diarrhoea,
      the summary OR was 0.44 (95% CI = 0.30-0.66). CONCLUSIONS: Our review suggests
      that supplementation with probiotics could be effective in increasing eradication
      rates of anti-H. pylori therapy, and could be considered helpful for patients
      with eradication failure. Furthermore, probiotics show a positive impact on H.
      pylori therapy-related side effects.

PMID- 17229241
TI  - GI Epidemiology: databases for epidemiological studies.
AB  - BACKGROUND: Large databases are being increasingly used for examining the
      epidemiology and outcomes of digestive and liver disorders. The complexity and
      rigor of the methods used to conduct these studies are often underestimated.
      AIMS: For the most commonly used databases, we provide a brief description of the
      contents, highlight strengths and weakness, and provide links for more detailed
      information. We also present a systematic approach to utilizing large databases
      for addressing research questions, highlighting commonly encountered study design
      issues, as well as strategies for resolving these issues. CONCLUSIONS: 1.
      Research using large databases requires the same essential skills needed to
      conduct research studies using other data sources. These include a rigorous study
      design, expertise in analytic methods, and relevant research questions. 2. The
      completeness and accuracy of information contained in the database must be
      assessed. Methods for improving the quality and completeness of this information
      should be considered. 3. Despite similarities among large databases, gaining
      insight and experience into the structure and content of each database is
      essential. Key points *Large databases can be a powerful source of information to
      examine the clinical epidemiology and outcomes of digestive and liver disorders.
      * Research using large databases requires the same essential skills needed to
      conduct research studies using other data sources. These include a rigorous study
      design, expertise in analytic methods, and relevant research questions. * The
      completeness and accuracy of information contained in the database must be
      assessed. Methods for improving the quality and completeness of this information
      should be considered. * Despite similarities among large databases, gaining
      insight and experience into the structure and content of each database is
      essential. * Examples of commonly used large databases are presented with a
      synopsis of information contained in the database, as well as strengths and
      limitations of using the database for research.

PMID- 17229242
TI  - A randomized double-blind placebo-controlled trial of Lactobacillus GG for
      abdominal pain disorders in children.
AB  - BACKGROUND: Functional abdominal pain disorders (FAPD) are common in school-aged
      children; however, there is no reliable treatment. AIM: To determine the efficacy
      of Lactobacillus rhamnosus GG (LGG) for treating FAPD in children. METHODS: A
      total of 104 children who fulfilled the Rome II criteria for functional dyspepsia
      (FD), or irritable bowel syndrome (IBS), or functional abdominal pain (FAP) were
      enrolled in a double-blind, randomized controlled trial in which they received
      LGG (n = 52), or placebo (n = 52) for 4 weeks. RESULTS: For the overall study
      population, those in the LGG group were more likely to have treatment success (no
      pain) than those in the placebo group (25% vs. 9.6%, relative benefit (RB) 2.6,
      95% confidence interval (CI): 1.05-6.6, number needed to treat (NNT) 7, 95% CI: 4
      123). For children with IBS (n = 37), those in the LGG group were more likely to
      have treatment success than those in the placebo group (33% vs. 5%, RB 6.3, 95%
      CI: 1.2-38, NNT 4, 95% CI: 2-36) and reduced frequency of pain (P = 0.02), but
      not pain severity (P = 0.10). For the FD group (n = 20) and FAP group (n = 47),
      no differences were found. CONCLUSION: The LGG appears to moderately increase
      treatment success, particularly among children with IBS.

PMID- 17229243
TI  - Comparison of the effects of immediate-release omeprazole oral suspension,
      delayed-release lansoprazole capsules and delayed-release esomeprazole capsules
      on nocturnal gastric acidity after bedtime dosing in patients with night-time
      GERD symptoms.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GERD) patients on proton pump
      inhibitors before breakfast or dinner have acid recovery at night. Bedtime
      immediate-release omeprazole (IR-OME) demonstrated better control of nocturnal pH
      than pantoprazole before dinner. AIM: To compare repeated once daily bedtime
      dosing of IR-OME, lansoprazole and esomeprazole on nocturnal gastric acidity.
      METHODS: Open-label, randomized, crossover study enrolling 54 patients with
      nocturnal GERD symptoms comparing IR-OME, lansoprazole and esomeprazole at steady
      state for nocturnal acid breakthrough (NAB), percentage of time with gastric pH >
      4 and median gastric pH. RESULTS: Onset of nocturnal acid control with IR-OME was
      rapid. During the first half of the night, percentage of time with gastric pH > 4
      and median gastric pH were significantly higher after IR-OME compared to
      esomeprazole or lansoprazole (P < 0.001, both comparisons). Over the 8-h night
      time period, acid control with IR-OME was significantly better than lansoprazole
      (P < 0.001), and comparable to esomeprazole. IR-OME reduced NAB compared with
      esomeprazole and lansoprazole (61% vs. 92% and 92%; P < 0.001, both comparisons).
      CONCLUSIONS: Bedtime IR-OME provided more rapid control of night-time gastric pH
      and decreased NAB compared with esomeprazole and lansoprazole. Nocturnal acid
      control with IR-OME was superior to lansoprazole and comparable to esomeprazole.
      Bedtime dosing with IR-OME may be effective for patients with night-time
      heartburn.

PMID- 17229244
TI  - Screening for liver disease using non-invasive biomarkers (FibroTest, SteatoTest
      and NashTest) in patients with hyperlipidaemia.
AB  - BACKGROUND: Mortality related to complications of cirrhosis is increasing in
      patients with insulin-resistance factors. Hyperlipidaemic patients have multiple
      risk factors of insulin resistance. It is impossible to perform liver biopsy in
      such a large number of hyperlipidaemic patients to identify patients with
      advanced liver fibrosis or with steatohepatitis (non-alcoholic steatohepatitis,
      NASH). AIMS: To use the non-invasive biomarkers, FibroTest (FT), SteatoTest and
      NashTest, and to assess the prevalence of advanced liver disease in a large
      population of hyperlipidaemic patients. METHODS: A consecutive cohort of
      hyperlipidaemic patients was followed prospectively in a lipid centre and the
      sera were analysed retrospectively. RESULTS: A total of 2834 subjects were
      included: 1909 hyperlipidaemic patients and 925 blood donors (BD). Advanced
      fibrosis was identified by FT in 53/1909 (2.8%) hyperlipidaemic patients vs.
      0/925 BD (0%) (P < 0.0001); advanced steatosis in 569/1893 hyperlipidaemic
      patients (30.1%) vs. 8/164 (4.9%) BD (P < 0.0001) and NASH in 132/1893 (7%) vs.
      0/164 (0%), respectively (P < 0.0001). There was a highly significant and linear
      association between the number of metabolic syndrome factors and liver disease
      prevalence - the highest being for type 2 diabetics: advanced steatosis 66%, NASH
      24% and advanced fibrosis 6%. CONCLUSIONS The prevalence of fibrosis, steatosis
      and NASH in hyperlipidaemic patients appears to be high (3%, 30% and 7%,
      respectively). Biomarkers could be useful for screening of advanced fibrosis and
      NASH in patients with several metabolic syndrome factors, to prevent liver
      mortality.

PMID- 17229245
TI  - Inadequate dietary intake but not renal tubular acidosis is associated with bone
      demineralization in primary biliary cirrhosis.
AB  - BACKGROUND: Metabolic bone disease associated with primary biliary cirrhosis
      (PBC) is inadequately characterized. Renal tubular acidosis (RTA) may lead to
      bone loss through chronic mobilization of skeletal calcium salts to buffer
      increased acid load. AIM: To evaluate the prevalence of RTA in PBC and establish
      the relationships among bone mineral density (BMD), renal function and
      nutritional status. METHODS: We enrolled 69 female patients with compensated PBC
      and 35 control patients with chronic hepatitis C. RTA was searched in all
      patients, and 24-h dietary recalls were collected at enrolment. BMD was measured
      by dual-energy X-ray absorptiometry at the femur neck, lumbar spine and radius
      ultradistalis sites. RESULTS: No patients received a diagnosis of RTA. BMD values
      (Z-scores) showed only little deviation from normal population with no difference
      between PBC and controls. Osteopoenic PBC patients (T-score < 1) showed
      significantly lower daily phosphorus intake [median: 672 (288-1374) vs. 921 (253
      1923) mg/day; P = 0.037], with a trend towards lower caloric intake than their
      nonosteopoenic counterparts. CONCLUSIONS: Renal tubular acidosis is uncommon in
      compensated PBC. Cholestasis is not associated with an increased risk of bone
      demineralization. Inadequate dietary intake may be a preventable factor
      contributing to bone loss in PBC.

PMID- 17229246
TI  - Modern management of non-Hodgkin lymphoma in HIV-infected patients.
AB  - Patients infected with human immunodeficiency virus (HIV) are at greater risk of
      developing non-Hodgkin lymphoma than the general population and aggressive B-cell
      lymphoma has become one of the most common of the initial acquired
      immunodeficiency syndrome (AIDS)-defining illnesses. This review considers the
      prognostic factors and new approaches to the treatment of patients with AIDS
      related lymphoma (ARL). As highly active antiretroviral therapy (HAART) became
      available, the survival of many ARL patients has become comparable to that of HIV
      negative patients. This is partly due to the decrease in the incidence of
      opportunistic infections and improved prognosis. Both developments can also be
      attributed to new treatment strategies for ARL, such as the use of effective
      infusional regimens, Rituximab combinations and high-dose therapy with autologous
      stem-cell transplantation for relapsed disease. However, unresolved issues
      persist, such as the optimal therapy for patients with Burkitt ARL or central
      nervous system involvement.

PMID- 17229247
TI  - The new era: going paperless with clinical software for physicians.

PMID- 17229248
TI  - Establishment of a stroke unit in a district hospital: review of experience.
AB  - BACKGROUND: The experience and outcomes of co-locating acute stroke and stroke
      rehabilitation care in a district hospital were reviewed. METHOD: Information for
      patients admitted to Blacktown and Mt Druitt Hospitals before and after setting
      up an acute stroke unit (SU) (12 months data for each period), including
      mortality and length of stay (LOS) at the hospital were obtained from various
      sources, including the diagnosis-related group and subacute and non-acute casemix
      databases. RESULTS: There was a significant reduction of mortality (18 vs 10%; P
      = 0.01) and reduced total LOS (46 vs 39 days; P = 0.01) with similar functional
      outcomes in the post-SU period. Fifty per cent of patients were unable to access
      the acute SU. Patients admitted into the SU had lower mortality (5 vs 14%; P =
      0.01) and were also discharged from hospital earlier (35 vs 54 days; P = 0.01)
      than patients admitted into general wards during the post-SU period. Thirty-four
      per cent of patients received rehabilitation within the rehabilitation facility
      in the post-SU period compared with 19% in the pre-SU period. CONCLUSION: The
      Blacktown experience showed the feasibility of establishing a co-located SU
      within rehabilitation facility with good outcomes as illustrated by the
      significant reduction in the stroke mortality, a reduction in the total LOS and
      an increase in the number of patients receiving rehabilitation post-stroke.

PMID- 17229249
TI  - Metabolic effects of pioglitazone and rosiglitazone in patients with diabetes and
      metabolic syndrome treated with metformin.
AB  - BACKGROUND: Metformin is considered the gold standard for type 2 diabetes
      treatment as monotherapy and in combination with sulphonylureas and insulin,
      whereas the combination of metformin with thiazolidinediones is relatively less
      studied. The aim of the present study was to assess the differential effect on
      glycaemic metabolism and lipid variables of the combination of metformin plus
      pioglitazone or metformin plus rosiglitazone in diabetic patients with metabolic
      syndrome. METHODS: All patients began metformin and were randomized to receive
      pioglitazone or rosiglitazone for 12 months. We assessed body mass index,
      glycated haemoglobin, fasting plasma glucose, postprandial plasma glucose,
      fasting plasma insulin, postprandial plasma insulin, homeostasis model assessment
      index, total cholesterol, low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B.
      RESULTS: Significant decreases in glycated haemoglobin, fasting plasma glucose,
      postprandial plasma glucose, fasting plasma insulin, and postprandial plasma
      insulin were seen after 9 and 12 months in both groups. Homeostasis model
      assessment index improved at 12 months in both groups. Significant total
      cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, triglycerides, apolipoprotein A-I, and apolipoprotein B improvement
      was observed in pioglitazone group after 12 months, but not in the rosiglitazone
      group. These variations were significant between groups. CONCLUSION: The
      combination of metformin plus thiazolidinediones was able to improve glycaemic
      control compared with previous therapy. Pioglitazone was associated with a
      significant improvement in lipid and lipoprotein variables.

PMID- 17229250
TI  - Readmission and survival following hospitalization for chronic obstructive
      pulmonary disease: long-term trends.
AB  - BACKGROUND: Exacerbations requiring hospital admission for chronic obstructive
      pulmonary disease (COPD) contribute to a decline in health status and are costly
      to the community. Long-term trends in admissions and associated outcomes are
      difficult to establish because of frequent readmissions, high case fatality and
      potential diagnostic transfer between COPD and asthma. The Western Australian
      Data Linkage System provides a unique opportunity to examine admissions for
      patients with COPD over the long term. METHOD: Nineteen years of hospital
      morbidity data, based on International Classification of Diseases-9 criteria were
      extracted from the Western Australian Data Linkage System (1980-1998) and merged
      with mortality records to examine trends in hospital admissions for COPD.
      RESULTS: The rate of hospital admissions for COPD has declined overall and the
      rate of first presentation declined in men and remained constant in women. The
      risk of readmission increased throughout the period (P < 0.0001) and more than
      half of all admissions were followed by readmission within a year. Median
      survival following first admission was 6 years (men 5 years; women 8 years). Age,
      sex and International Classification of Diseases subcategory each showed an
      independent effect on the risk of mortality (P < 0.0001). The poorest survival
      was in patients subcategorized as emphysema. For patients with multiple
      admissions, the likelihood of cross-over between COPD and asthma was high and
      increased with the total number of admissions. CONCLUSION: The rate of admission
      for COPD has declined in Western Australia; however, the resource burden will
      continue to increase because of the ageing population. This has policy
      implications for the development of acute care treatment programmes for COPD.

PMID- 17229251
TI  - Recruitment of volunteers to improve vitality in the elderly: the REVIVE study.
AB  - BACKGROUND: Delirium is a common problem for frail, older patients in hospital
      and a marker of poor outcome and mortality. The aim of this study was to test a
      volunteer-mediated delirium prevention programme for efficacy, cost-effectiveness
      and sustainability on an Australian geriatric ward. METHODS: Two controlled
      before-and-after studies were conducted. In study 1, 37 patients (>70 years,
      admitted to the geriatric wards) were enrolled during 5 months in 2003 for
      intensive individual study. Twenty-one patients received usual care and 16
      patients received the volunteer-mediated intervention of daily orientation,
      therapeutic activities, feeding and hydration assistance, vision and hearing
      protocols. In study 2, we examined the effects of a general implementation for
      the whole department by measuring use of assistants in nursing, who were employed
      for individual nursing of delirious patients. RESULTS: In study 1, we found a
      lower incidence (intervention vs control, 6.3% vs 38%; P = 0.032) and lower
      severity of delirium (1.2 vs 5.1; P = 0.045). There was a trend towards decreased
      duration of delirium (5.0 vs 12.5; P = 0.64). In study 2, use of assistants in
      nursing was reduced by 314 h per month suggesting a total annual saving of
      129,186 Australian dollars for the hospital. CONCLUSION: The programme prevents
      delirium and improves outcomes for elderly inpatients. Cost-effectiveness
      supports the continuation of the programme and extension to other geriatric
      units.

PMID- 17229253
TI  - The electronic, 'paperless' medical office; has it arrived?
AB  - Modern information technology offers efficiencies in medical practice, with a
      reduction in secretarial time in maintaining, filing and retrieving the paper
      medical record. Electronic requesting of investigations allows tracking of
      outstanding results. Less storage space is required and telephone calls from
      pharmacies, pathology and medical imaging service providers to clarify the hand
      written request are abolished. Voice recognition software reduces secretarial
      typing time per letter. These combined benefits can lead to significantly reduced
      costs and improved patient care. The paperless office is possible, but requires
      commitment and training of all staff; it is preferable but not absolutely
      essential that at least one member of the practice has an interest and some
      expertise in computers. More importantly, back-up from information technology
      providers and back-up of the electronic data are absolutely crucial and a
      paperless environment should not be considered without them.

PMID- 17229252
TI  - Effect of leflunomide on the peripheral nerves in rheumatoid arthritis.
AB  - BACKGROUND: The objective of this study was to determine the neurophysiological
      effects of leflunomide on peripheral nerves in rheumatoid arthritis. METHODS: We
      conducted a prospective cohort trial of 32 patients with rheumatoid arthritis
      with 16 patients receiving leflunomide treatment and 16 receiving other disease
      modifying anti-rheumatic drug therapies. Clinical, laboratory and
      neurophysiological measurements were used to determine the presence of a
      peripheral neuropathy in these patients at study entry and then after a further 3
      and 6 months. RESULTS: Fifty-four per cent of the leflunomide group and 8% of the
      control group had an increase in their neuropathy symptom score 6 months into the
      study (P = 0.01). No correlation was found between the electrophysiological
      findings and the clinical symptoms. There was no significant difference between
      the two groups in upper and lower limb sensory and motor amplitudes and
      conduction velocities recorded at 3 and 6 months. One patient developed both
      clinical and neurophysiological evidence of a peripheral neuropathy 5 months into
      the study that improved after cessation of leflunomide therapy and cholestyramine
      washout. CONCLUSION: After 6 months of exposure we found that leflunomide was
      associated with an apparent increase in the clinical symptoms of peripheral
      neuropathy in patients with rheumatoid arthritis. These symptoms did not
      correlate with neurophysiological studies.

PMID- 17229254
TI  - Non-invasive positive pressure ventilation for acute respiratory failure:
      justified or just hot air?
AB  - Non-invasive positive pressure ventilation (NIV) is the provision of mechanical
      positive airway pressure ventilatory support through the patient's upper airway
      through mask interface. Conditions in which it has been shown to be effective are
      acute cardiogenic pulmonary oedema and acute hypercapnic exacerbations of chronic
      obstructive pulmonary disease. In such conditions, NIV is associated with reduced
      intensive care unit demands, a reduction in intubation rates, reduced health-care
      expenditure and improved survival. Other conditions, such as hypercapnia of other
      cause, hypoxaemic respiratory failure and acute asthma, have supportive, but less
      conclusive data. Indications, contraindications and guidelines for the use of NIV
      are discussed.

PMID- 17229255
TI  - Managing scientific uncertainty in health legislation.
AB  - Legislation and regulation of biomedical research is seldom a one-off process
      since biomedical science evolves rapidly, dynamically and often unpredictably.
      This paper discusses the challenges faced by regulators who need to produce
      legislation and policy in rapidly changing fields and outlines some practical
      suggestions for managing law reform and policy-making under these circumstances.

PMID- 17229256
TI  - Diagnosing cancer: changing patterns of care.
AB  - We prospectively assessed 100 consecutive inpatient referrals made to the Medical
      Oncology Unit. The major end-point was the time to diagnostic biopsy. Referral
      trends and treatment outcomes were also recorded. Our results show that the
      referring units undertook the diagnostic process in the vast majority and the
      time to inpatient diagnostic biopsy has fallen from 10 to 4.6 days, compared with
      a similar study 13 years ago. This emphasizes the changing role of the oncologist
      in current day multidisciplinary cancer care.

PMID- 17229257
TI  - Allogeneic bone marrow transplant for refractory mediastinal germ cell tumour:
      possible evidence of graft-versus-tumour effect.
AB  - Mediastinal germ cell tumours (GCT) carry a poor prognosis, particularly after
      relapse. We have reviewed the published reports of current treatments and
      describe a case with a cure after an allogeneic bone marrow transplant, which is
      not reported in the current published data. We believe that GCT may be
      susceptible to a graft-versus-tumour effect and suggest that patients with
      relapsed GCT be considered for allogeneic transplantation.

PMID- 17229258
TI  - Yam bean seed poisoning mimicking cyanide intoxication.
AB  - BACKGROUND: Yam bean is a common food in southern Taiwan. However, its seeds are
      rarely consumed. We describe five patients of yam bean seed poisoning in Taiwan,
      one of them life-threatening. CLINICAL PRESENTATION: The five patients presented
      with perioral numbness, nausea and vomiting after eating a same soup made from
      yam bean seeds. One of them, a 54-year-old woman, had difficulty breathing and
      lost consciousness. Physical examination showed dilated pupils and coma with no
      focal neurological signs. The initial blood pressure was normal. Laboratory data
      showed a severe anion gap metabolic acidosis, with a serum lactate level of 185
      mg/dL. An initial diagnosis of cyanide intoxication was considered and she was
      given sodium nitrite and sodium thiosulfate i.v. Hypotension ensued shortly
      afterwards and pulmonary artery catheterization showed a decreased cardiac index.
      Aggressive fluid and inotropic therapy were given and the patient eventually
      recovered. The other four patients suffered only minor gastrointestinal and
      neurological symptoms and received supportive treatment. Cyanide levels were
      negative in all five patients. CONCLUSION: Yam bean seed poisoning can cause
      acute metabolic acidosis and altered mental status, which could be confused with
      acute cyanide intoxication from a cyanogenic glycoside-containing plant. To our
      knowledge, this is the first outbreak of yam bean seed poisoning reported in the
      English published work.

PMID- 17229260
TI  - Recurrent needle-tract metastases of hepatocellular carcinoma following fine
      needle aspiration.

PMID- 17229259
TI  - Thromboembolism and breast cancer: the hidden risk for patient and physician.

PMID- 17229261
TI  - Non-surgical cause of hydronephrosis: retroperitoneal fibrosis.

PMID- 17229262
TI  - Disseminated zygomycosis.

PMID- 17229263
TI  - Nephrogenic fibrosing dermopathy: a new clinical entity mimicking scleroderma.

PMID- 17229264
TI  - Severe hypoglycaemic unawareness in a patient with insulinoma.

PMID- 17229265
TI  - Gender preference may be a barrier to colorectal screening.

PMID- 17229270
TI  - Cluster A personality disorders: considering the 'odd-eccentric' in psychiatric
      nursing.
AB  - Psychiatric nurses are familiar with the concept of personality disorder because
      of their contact with persons with the most common personality disorder in
      clinical settings - borderline type, who frequently engage mental health
      services. Perhaps it is this familiarity that has focused research and clinical
      attention on borderline personality disorder compared with the other personality
      disorders. The significance of cluster A personality disorders for nursing is
      multifaceted because of their severity, prevalence, inaccurate diagnosis, poor
      response to treatment, and similarities to axis I diagnoses. Despite this,
      literature reviews have established that relatively few studies have focused on
      the treatment of the cluster A personality disorders - paranoid, schizotypal, and
      schizoid - resulting in a dearth of evidence-based interventions for this group
      of clients. A discussion of these disorders in the context of personality
      disorder and their individual characteristics demonstrates the distinctive and
      challenging engagement techniques required by psychiatric nurses to provide
      effective treatment and care. It is also strongly indicated that the discipline
      of psychiatric nursing has not yet begun to address the care of persons with
      cluster A personality disorders.

PMID- 17229269
TI  - Critical evaluation of the use of research tools in evaluating quality of life
      for people with schizophrenia.
AB  - Schizophrenia may lead to impairments in many aspects of life, including
      physical, cognitive, and role functioning. The subjective quality of life of
      people with schizophrenia has been shown to be lower than in the general
      population and appropriate patient-assessed health outcome measures are necessary
      to capture the distress and disability experienced by people living with a
      serious mental illness. Although psychiatry has been slow to become involved in
      quality of life measurement, the use of quality of life instruments has now been
      recognized as a means of evaluating the outcome of care interventions, in terms
      of symptoms and functioning. This paper evaluates the effectiveness of two widely
      used instruments: The Medical Outcomes Study Short Form Health Survey (SF-36) and
      The Lancashire Quality of Life Profile (LQoLP) in terms of reliability and
      validity in measuring the quality of life of people with schizophrenia. The LQoLP
      appeared to be best suited for evaluation of care programmes, whereas the SF-36
      was more appropriate for medical trials, comparisons between patient groups, and
      assessment of the direct consequences of treatment on health and function.
      Subjective quality of life should, however, be considered to be distinct from
      clinical status and quality of life assessment should include the broadest range
      of indicators, to reflect the holistic ethos of mental health nursing.

PMID- 17229267
TI  - Maintenance of antigen-specific immunological memory through variable regions of
      heavy and light chains of anti-idiotypic antibody.
AB  - Immunological memory is characterized by a quick and enhanced immune response
      after re-exposure to the same antigen. To explain the mechanism involved in
      generation and maintenance of immunological memory, we had earlier proposed a
      hypothesis involving the relay of memory by idiotypic and anti-idiotypic B cells.
      The peptidomimic present in the hypervariable region of anti-idiotypic antibody
      was hypothesized to carry forward immunological memory. In the present work, we
      provide evidence supporting a role for the anti-idiotypic antibody in eliciting
      antigen-specific B-cell and T-cell responses. Employing the idiotypic monoclonal
      antibody (Ab(1)) specific for haemagglutinin (H) protein of rinderpest virus,
      Ab(2beta) was generated, which possesses an internal image of the H protein in
      the region between amino acids 527 and 556. We demonstrate that antigen-specific
      memory is perpetuated by immunization with Ab(2), as shown by maintenance of
      antigen-specific T-cell responses upon restimulation in vitro of Ab(2) immune
      splenocytes by antigen-presenting cells expressing H protein or pulsed with H
      protein-derived peptides. We have also shown that boosting with antigen-specific
      anti-idiotypic B cells generates a memory response in antigen-primed mice.
      Evidence has been provided for the existence of an antigen-specific B-cell
      idiotypic network in the body that supports the perpetuation of immunological
      memory as proposed in the relay hypothesis.

PMID- 17229266
TI  - CD4+ CD25+ regulatory T cells in human pregnancy: development of a Treg-MLC
      ELISPOT suppression assay and indications of paternal specific Tregs.
AB  - The current study was aimed at developing a one-way mixed leucocyte culture
      enzyme-linked immunospot (MLC-ELISPOT) assay for the study of CD4(+) CD25(+)
      regulatory T (T(reg)) cells and applying this method in the study of antifetal
      immune reactions during human pregnancy. Twenty-one pregnant women and the
      corresponding fathers-to-be, and 10 non-pregnant control women and men,
      participated in the study. CD4(+) CD25(+) cells were isolated from peripheral
      blood mononuclear cells (PBMC) by immunomagnetic selection. Maternal/control PBMC
      were stimulated with paternal or unrelated PBMC in MLC. Secretion of interleukin
      4 (IL-4) and interferon-gamma (IFN-gamma) from responder cells, with or without
      the presence of autologous T(reg) cells, was analysed by ELISPOT. PBMC from
      pregnant women showed increased secretion of IL-4 compared to controls. In
      pregnant and non-pregnant controls, T(reg) cells suppressed IFN-gamma reactivity
      against paternal and unrelated alloantigens. Interestingly, T(reg) cells
      suppressed IL-4 secretion against paternal but not unrelated alloantigens during
      pregnancy. We have successfully developed a model for studying T(reg) cells in
      antifetal cytokine reactions during pregnancy. Results indicate that T(reg) cells
      contribute to strict regulation of both T helper type 1-like and type 2-like
      antifetal immune reactions. Interestingly, T helper type 2-like cells specific to
      unrelated alloantigens are able to escape the suppression of T(reg) cells, which
      would allow for IL-4, alongside CD4(+) CD25(+) T(reg) cells, to control
      potentially detrimental IFN-gamma reactions during pregnancy.

PMID- 17229271
TI  - Mental health nurses' experiences of schizophrenia rehabilitation in China and
      India: a preliminary study.
AB  - Nursing methods based on Western models may not be culturally relevant to
      patients from ethnic minority groups or other countries. In order to meet the
      needs of all patients, more research is needed to understand the cultural and
      social factors that influence nursing approaches. This paper reports preliminary
      open-ended discussions with mental health nurses in China and India in order to
      gain insights into the cultural and social issues that surround social
      rehabilitation of patients with schizophrenia. Rehabilitation methods included
      cognitive behavioural therapy, psychosocial methods, and employment/vocational
      training. Several cultural and social issues drive the rehabilitation process in
      both countries, including the use of traditional medicine and healers, emphasis
      on family involvement, stigma, gender inequality, and lack of resources.
      Participants in both countries were working hard to tackle some of these issues,
      but also expressed need for improved resources. The study provides an insight
      into the cultural and social factors that shape schizophrenia rehabilitation in
      China and India, and serves as a baseline for further research about nursing
      across cultures. The study also highlights the marked differences in attitudes,
      values, and behaviours across cultural groups that need to be considered by
      nursing professionals to ensure that services are culturally competent.

PMID- 17229272
TI  - Evaluation of a forensic psychiatric setting to provide a graduate nurse
      programme.
AB  - There has been growth in the number and diversity of models of Australian
      graduate nurse programmes in psychiatric nursing. Programmes have also been
      established in specialist areas, and evidence is needed regarding best models of
      graduate nurse programmes and the ability of specialist areas to prepare nurses
      for psychiatric nursing. This paper reports on a qualitative project that
      examined the adequacy of a forensic psychiatric hospital to provide a graduate
      nurse programme. Individual, semistructured interviews were undertaken with
      nurses participating in the programme, and nurses who had completed the programme
      and had remained at the hospital or were nursing in other areas. Participants
      identified that the environment was safe and supportive of professional practice
      and development, and that skilled nurses were willing to encourage and teach
      graduates. Processes such as orientation, preceptorship and academic study were
      appreciated; however, their colleagues' willingness to be available, to teach,
      and to support were more valued. Participants reported that they felt confident
      and prepared as psychiatric nurses. Although limitations of undertaking a
      graduate nurse programme in a forensic setting were identified, the participants
      from past programmes who had gone on to work in other services did not report
      that their nursing careers had been disadvantaged. It can be concluded that as
      long as the context of the programme has adequate resources to support and assist
      graduates to develop the skills, knowledge and attitudes of psychiatric nursing,
      then the specialist nature may not be a limitation.

PMID- 17229273
TI  - Self-reported consequences and needs for support associated with abuse in female
      users of psychiatric care.
AB  - The aims of the study were to investigate the prevalence of adult abuse in female
      users of psychiatric care, the relationship between abuse and self-esteem and
      self-reported consequences of abuse, and women's self-reported needs of support.
      A total of 1382 women participated in the study. A self-administrated anonymous
      questionnaire with both closed-ended and open-ended questions was used.
      Quantitative data were analysed by mainly descriptive statistics and qualitative
      data were analysed by content analysis. Forty-six per cent (n = 638) of the women
      had been exposed to emotional, sexual, and/or physical abuse in adulthood. Twenty
      eight per cent (n = 385) reported experiences of moderate physical abuse, 27% (n
      = 373) reported threats of injury, and 20% (n = 277) reported threats of being
      killed. Further, 19% (n = 261) reported experience of sexual violence, and 12% (n
      = 164) had experiences of serious physical violence. Women who had been abused
      rated lower self-esteem than those who were not abused. Self-reported
      consequences of abuse included intrapersonal problems such as poor self-esteem,
      fears, anxiety, and worries but also problems in social relations especially with
      regard to close relationships and reliance to others. To a lesser extent, disease
      specific manifestations were reported. The needs of support included
      interventions directed to the experiences of abuse by professionals trained in
      the area, family interventions, self-help groups, medical care, legal support, or
      practical help to find new housing situations. It is concluded that female users
      of psychiatric care services constitute a vulnerable group with regard to abuse.
      To meet the women's needs, the care system has to adopt a perspective that
      includes personal, social, and societal factors.

PMID- 17229274
TI  - Critique of Falloon and the Optimal Treatment Project.
AB  - The Optimal Treatment Project advocated by Falloon has been demonstrated through
      the scientific research literature to be efficient and effective treatment
      strategies for people experiencing severe mental illness. For this reason, there
      is little critique of this approach. While the potential value of the project is
      acknowledged, it is important to identify the appropriateness of the model for
      specific services and to understand comprehensively the resources necessary for
      successful implementation. The aim of this paper is to review the literature in
      relation to the Optimal Treatment Project with a view to exploring the
      complexities associated with the model. It is concluded that the involvement of
      multiple stakeholders, including consumers of mental health services, should
      become an essential element of any implementation strategy.

PMID- 17229275
TI  - Perceptions of the concept of health among nurses working in mental health
      services: a phenomenographic study.
AB  - A new understanding of the concept of health is needed to meet the goal of mental
      health nursing, which besides reducing disease is to strengthen the patient's
      health. The aim of the present study was to describe perceptions of the concept
      of health among nurses working in mental health services. Twelve Swedish nurses
      working in mental health services were interviewed and data were analysed with a
      phenomenographic approach. The nurses expressed 10 perceptions, which constituted
      three description categories: autonomy, process, and participation. The result
      showed that health was more than absence of disease. Simultaneously, perceptions
      were expressed indicating that health was viewed as absence of disease, which
      implies that the concept is not sufficiently defined. The result emphasizes the
      need to clarify the concept of health if it is to be used as a goal in mental
      health nursing and to integrate a clarified definition of health at all
      hierarchical levels in mental health care services.

PMID- 17229276
TI  - Evidence-based mental health nursing in Australia: our history and our future.
AB  - This paper will develop a discussion related to evidence-based knowledge for
      mental health nursing, arguing for a historical component to be included in the
      comprehensive degree programme that will offer significant insights into mental
      health nursing knowledge from historical information and constructing
      implications for contemporary practice. Our understanding of the present is
      clearer by this looking back and forth and by adding meaning (and what the
      meanings mean) to what historically preceded. It allows the history of psychiatry
      to be a much more productive, useful, and a continual source of wisdom for the
      here and now. This blending of past knowledge with contemporary inquiry can offer
      depth in mental health nursing practices by forming a context for practice for
      the beginning nurse practitioner.

PMID- 17229277
TI  - Family caregivers' satisfaction with home care for mental illness in Taiwan.
AB  - In Taiwan, family caregivers play a crucial role in the treatment of patients
      with mental illness. Attention to family caregivers' satisfaction with home care
      for mental illness could have a significant impact on the well-being of family
      caregivers, as well as on the health of the patients with mental illness for whom
      they care. A descriptive, cross-sectional design has been used to assess the
      level of family caregivers' satisfaction with home care for mental illness since
      the implementation of the National Health Insurance (NHI) in Taiwan, and to
      identify the family caregivers' unmet needs for home care in cases of mental
      illness. Data were collected using the self-administrated questionnaire completed
      by a convenience sample of 75 primary family caregivers of the patients with
      mental illness from a psychiatric hospital in Taipei, Taiwan. The result showed
      that most family caregivers were highly satisfied with home care provided to them
      and their relative with mental illness. Timeliness of home care provided in an
      emergency was the most prevalent unmet need. The implementation of the NHI has
      improved family caregivers' perceptions of costs of home care services. There is
      a need to improve NHI policy and home care programmes to provide more holistic
      services for the patients with mental illness and their family.

PMID- 17229278
TI  - Crimp morphology in relaxed and stretched rat Achilles tendon.
AB  - Fibrous extracellular matrix of tendon is considered to be an inextensible
      anatomical structure consisting of type I collagen fibrils arranged in parallel
      bundles. Under polarized light microscopy the collagen fibre bundles appear
      crimped with alternating dark and light transverse bands. This study describes
      the ultrastructure of the collagen fibrils in crimps of both relaxed and in vivo
      stretched rat Achilles tendon. Under polarized light microscopy crimps of relaxed
      Achilles tendons appear as isosceles or scalene triangles of different size.
      Tendon crimps observed via SEM and TEM show the single collagen fibrils that
      suddenly change their direction containing knots. The fibrils appear partially
      squeezed in the knots, bent on the same plane like bayonets, or twisted and bent.
      Moreover some of them lose their D-period, revealing their microfibrillar
      component. These particular aspects of collagen fibrils inside each tendon crimp
      have been termed 'fibrillar crimps' and may fulfil the same functional role. When
      tendon is physiologically stretched in vivo the tendon crimps decrease in number
      (46.7%) (P<0.01) and appear more flattened with an increase in the crimp top
      angle (165 degrees in stretched tendons vs. 148 degrees in relaxed tendons,
      P<0.005). Under SEM and TEM, the 'fibrillar crimps' are still present, never
      losing their structural identity in straightened collagen fibril bundles of
      stretched tendons even where tendon crimps are not detectable. These data suggest
      that the 'fibrillar crimp' may be the true structural component of the tendon
      crimp acting as a shock absorber during physiological stretching of Achilles
      tendon.

PMID- 17229279
TI  - Regional specialization of rat quadriceps myosin heavy chain isoforms occurring
      in distal to proximal parts of middle and deep regions is not mirrored by citrate
      synthase activity.
AB  - Myosin heavy chain (MHC) isoform content and citrate synthase (CS) activities
      were measured in the Quadriceps femoris (QF) muscle of 18 female rats. The muscle
      group was divided into superficial, middle and deep, distal, central and proximal
      parts. MHC IIb and IIx were more abundant in superficial regions (P<0.05) with
      low CS activities compared with deeper parts. The deeper parts expressed all four
      isoforms (MHC IIb, MHC IIx, MHC IIa and MHC I), with a concomitantly higher CS
      activity. MHC I, MHC IIa and MHC IIb isoform content varied significantly along
      the length of the deep regions. Only MHC IIb and CS activity in the proximal
      middle part correlated (negatively) with each other. This study showed that the
      QF has regional specialization and that standardization of sampling site is
      important. Furthermore, CS activity and MHC isoforms are only loosely associated,
      or not at all.

PMID- 17229280
TI  - Differential modulation of myosin heavy chain phenotype in an inactive extensor
      and flexor muscle of adult rats.
AB  - The effects of chronic neuromuscular inactivity on the phenotype and size of
      muscle fibres in a fast ankle extensor (medial gastrocnemius, MG) and a fast
      ankle flexor (tibialis anterior, TA) muscle of the rat hindlimb were determined.
      Inactivity was produced by spinal cord isolation (SI), i.e. complete spinal cord
      transections at a mid-thoracic and high sacral level and bilateral
      deafferentation between the transection sites. After 90 days of SI, the MG and TA
      muscle weights were 53 and 45% lower than in age-matched controls. Overall mean
      fibre sizes in the deep (close to the bone) and superficial (away from the bone)
      regions were approximately 60 and 65% smaller in the MG and approximately 40 and
      50% smaller in the TA of SI than control rats, respectively. The myosin heavy
      chain (MHC) composition shifted towards the faster isoforms after SI: the MG
      showed an increase in both types IIx (20%) and IIb (23%), whereas the TA showed a
      marked increase in type IIx (94%) and a decrease in type IIb (18%) MHC. Both
      muscles in SI rats showed no type IIa and only one MG muscle had approximately 5%
      type I MHC. These results show that prolonged inactivity has a stronger effect on
      a fast extensor compared with a fast flexor in the rat hindlimb. The larger
      decrease in mass and fibre size in the MG than the TA most probably reflects the
      larger impact of chronic inactivity on the normally more highly recruited
      extensor than flexor muscle. The primary shift to type IIb MHC in the MG and type
      IIx MHC in the TA indicate a different default mode for an inactive extensor vs.
      flexor muscle, and may reflect differing activity-independent neural influences,
      i.e. neurotrophic factors, on muscle fibre phenotype in extensors vs. flexors.

PMID- 17229281
TI  - Muscle architecture of biceps brachii, triceps brachii and supraspinatus in the
      horse.
AB  - Three muscles from the proximal equine forelimb were dissected in order to
      investigate their potential to contribute to proximal limb mechanics. Muscle
      mass, fibre length, tendon mass and tendon length were measured from biceps
      brachii, triceps brachii, supraspinatus and lacertus fibrosus (biceps lateral
      head mass 171-343.4 g and fibre length 0.5-0.8 cm; biceps medial head mass 283
      500 g and fibre length 2.2-4 cm; biceps tendon mass 121.8-260 g and tendon length
      35-44 cm; triceps long head mass 3200-6663 g and fibre length 19-26.3 cm; triceps
      lateral head mass 513.8-1240 g and fibre length 17.5-24 cm; triceps medial head
      mass 85.2-270.6 g and fibre length 9-16.8 cm; supraspinatus mass 793-1546 g and
      fibre length 4.7-12.4 cm; lacertus fibrosus mass 4.6-12.4 g and length 10-16 cm).
      Physiological cross-sectional area (PCSA) and maximum isometric force were
      estimated for each muscle, and moment arm measurements were taken at the shoulder
      and elbow joints. Biceps has a greater isometric force-generating capacity than
      supraspinatus. It also appears to have a larger shoulder moment arm, so could
      therefore have the potential to make a greater contribution to the shoulder
      moment than supraspinatus. Supraspinatus is likely to function primarily as a
      shoulder stabilizer rather than a shoulder extensor. Biceps also functions as an
      elbow flexor and data here indicate that it has a greater PCSA and isometric
      force-generating capacity than its antagonist triceps brachii. Calculation of
      tendon forces showed that the biceps tendon can withstand much greater forces
      than lacertus fibrosus. This study will enable further investigation into the
      interaction between energy recycling in elastic tissues and the generation and
      absorption of mechanical work by adjacent muscle groups in the equine forelimb.

PMID- 17229282
TI  - Assessing mechanical function of the zygomatic region in macaques: validation and
      sensitivity testing of finite element models.
AB  - Crucial to the interpretation of the results of any finite element analysis of a
      skeletal system is a test of the validity of the results and an assessment of the
      sensitivity of the model parameters. We have therefore developed finite element
      models of two crania of Macaca fascicularis and investigated their sensitivity to
      variations in bone material properties, the zygomatico-temporal suture and the
      loading regimen applied to the zygomatic arch. Maximum principal strains were
      validated against data derived from ex vivo strain gauge experiments using non
      physiological loads applied to the macaque zygomatic arch. Elastic properties of
      the zygomatic arch bone and the zygomatico-temporal suture obtained by
      nanoindentation resulted in a high degree of congruence between experimental and
      simulated strains. The findings also indicated that the presence of a zygomatico
      temporal suture in the model produced strains more similar to experimental values
      than a completely separated or fused arch. Strains were distinctly higher when
      the load was applied through the modelled superficial masseter compared with
      loading an array of nodes on the arch. This study demonstrates the importance of
      the accurate selection of the material properties involved in predicting strains
      in a finite element model. Furthermore, our findings strongly highlight the
      influence of the presence of craniofacial sutures on strains experienced in the
      face. This has implications when investigating craniofacial growth and
      masticatory function but should generally be taken into account in functional
      analyses of the craniofacial system of both extant and extinct species.

PMID- 17229283
TI  - Reactive changes of retinal astrocytes and Muller glial cells in kainate-induced
      neuroexcitotoxicity.
AB  - The aim of this study was to investigate reactive changes of astrocytes and
      Muller glial cells in rats subjected to kainate treatment, which leads to
      neuronal degeneration in the ganglion cell layer and the inner border of the
      inner nuclear layer as confirmed by labelling with Fluoro-Jade B, a marker for
      degenerating neurons and fibres. Both the astrocytes and the Muller glial cells
      reacted vigorously to kainate injection as shown by their up-regulated expression
      of nestin, glial fibrillary acidic protein and glutamine synthetase. A major
      finding was the induced expression of nestin together with glial fibrillary
      acidic protein beginning at 1 day post-injection of kainate. The marked nestin
      expression appeared to be most intense at 1 day and was sustained till 2 weeks as
      compared with the untreated/normal retina. Western blotting analysis confirmed a
      marked increase in expression of nestin, glial fibrillary acidic protein and
      glutamine synthetase as compared with untreated/normal retina. Double labelling
      study revealed that astrocytes and Muller glial cells expressed the radial glia
      marker nestin, and incorporated bromodeoxyuridine to re-enter into their cell
      cycle. The induced expression of these proteins in astrocytes and Muller glial
      cells indicated an induction of gliotic responses and de-differentiation that may
      be associated with regenerative efforts after kainate-induced injury. Indeed,
      with the acquisition of an immature molecular profile as manifested by the
      induced expression of brain lipid-binding protein and doublecortin in astrocytes
      and Muller glial cells, the potential of these cells to de-differentiate in
      retinal neurodegeneration is greatly amplified.

PMID- 17229284
TI  - Insights into the gyrification of developing ferret brain by magnetic resonance
      imaging.
AB  - The developmental mechanisms underlying the formation of human cortical
      convolutions (gyri and sulci) remain largely unknown. Genetic causes of
      lissencephaly (literally 'smooth brain') would imply that disorders in neuronal
      migration cause the loss of cortical convolutions. However, prior studies have
      suggested that loss of sulci and gyri can also arise from impaired proliferation,
      disrupted lamination and loss of intracortical connections. To gain further
      insight into the mechanisms underlying the formation of cortical convolutions, we
      examined the progressive brain development of the gyrencephalic ferret. In this
      study, we used magnetic resonance imaging to follow the temporal and spatial
      pattern of neuronal migration, proliferation and differentiation in relation to
      the onset and development of cortical convolutions. In this manner, we
      demonstrate that the onset of gyrification begins largely after completion of
      neuronal proliferation and migration. Gyrification occurs in a lateral to medial
      gradient, during the period of most rapid cerebral cortical growth. Cortical
      folding is also largely complete prior to myelination of the underlying cortical
      axons. These observations are consistent with gyrification arising secondary to
      cortical processes involving neuronal differentiation.

PMID- 17229285
TI  - Neurotrophin and Trk neurotrophin receptors in the inner ear of Salmo salar and
      Salmo trutta.
AB  - Neurotrophins (NTs) and their signal transducing Trk receptors play a critical
      role in the development and maintenance of specific neuronal populations in the
      nervous system of higher vertebrates. They are responsible for the innervation of
      the inner ear cochlear and vestibular sensory epithelia. Neurotrophins and Trks
      are also present in teleosts but their distribution in the inner ear is unknown.
      Thus, in the present study, we used Western-blot analysis and
      immunohistochemistry to investigate the expression and cell localization of both
      NTs and Trk receptors in the inner ear of alevins of Salmo salar and Salmo
      trutta. Western-blot analysis revealed the occurrence of brain-derived
      neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not nerve growth factor
      (NGF), as well as all three Trk receptors, i.e. TrkA, TrkB and TrkC, the
      estimated molecular weights of which were similar to those expected for mammals.
      Specific immunoreactivity for neurotrophins was detected mainly in the sensory
      epithelia. In particular, BDNF immunoreactivity was found in the maculae of the
      utricle and saccule, whereas NT-3 immunoreactivity was present in the sensory
      epithelium of the cristae ampullaris. As a rule the sensory epithelia of the
      inner ear lacked immunoreactivity for Trks, thus excluding possible mechanisms of
      autocrinia and/or paracrinia. By contrast, overlapping subpopulations of neurons
      in the statoacoustic ganglion expressed TrkA (about 15%), TrkB (about 65%) and
      TrkC (about 45%). The present results demonstrate that, as in mammals and birds,
      the inner ear of teleosts expresses the components of the neurotrophin-Trk
      system, but their roles remain to be elucidated.

PMID- 17229286
TI  - The lectin Dolichos biflorus agglutinin is a sensitive indicator of branching
      morphogenetic activity in the developing mouse metanephric collecting duct
      system.
AB  - The urine collecting duct system of the metanephric kidney develops by growth and
      branching morphogenesis of an unbranched progenitor tubule, the ureteric bud. Bud
      branching is mainly dichotomous and new branches form from existing branch tips,
      which are also the main sites of cell proliferation in the system. This
      behaviour, and the fact that some genes (e.g. Wnt11, Sox9) are expressed only in
      tips, suggests that tip cells are in a specific state of differentiation. In this
      report, we show that the lectin Dolichos biflorus agglutinin (DBA), hitherto
      regarded and used as a general marker of developing renal collecting ducts, binds
      to most of the duct system but does not bind to the very tips of growing
      branches. The zone avoided by DBA corresponds to the zone that expresses Wnt11,
      and the zone that shows enhanced cell proliferation. If branching of the ureteric
      bud of cultured embryonic kidneys is inhibited in organ culture, by blocking the
      kidney's endogenous glial cell-derived neurothrophic factor (GDNF)-based branch
      promoting signals, the DBA-binding zone extends to the very end of the tip but is
      lost from there when branching is re-activated. Similarly, if excess GDNF is
      provided to growing kidneys, the DBA-free zone expands. DBA-staining status
      therefore appears to be a sensitive indicator of the morphogenetic activity of
      the collecting duct system.

PMID- 17229287
TI  - Carbohydrate characterization of quail primordial germ cells during migration and
      gonadal differentiation.
AB  - A selection of lectins were used to study changes in the distribution of sugar
      residues in primordial germ cells (PGCs) during gonadal colonization and
      differentiation. Although the cytochemical characteristics of PGCs have been
      described in the chick, little is known about such characteristics in other avian
      species of interest to experimental biology. Therefore, we studied embryos of
      Japanese quail (Coturnix coturnix japonica) by light and laser confocal scanning
      microscopy, using the QH1 antibody as a tool to identify PGCs in both sexes and
      at all stages. LEA, WGA and RCA-I bound to PGCs in a similar way to QH1. LEA was
      the best marker for all stages. The presence of acid phosphatase and the intense
      reaction of LEA, WGA, RCA-I and WFA at the cell surface were shown to be a useful
      tool in the study of the migratory PGCs of the quail. Quails were sexed
      histologically in younger embryos than in chick; results were confirmed by PCR.
      The lectin-binding pattern changed drastically in differentiated gonads. Cell
      surface reactivity was almost entirely lost. Quail differentiating oogonia showed
      a characteristic binding pattern to QH1 and to the lectins WGA, RCA-I and WFA.
      Binding was observed in intense spots in the Golgi complex, and there was a
      specific PNA reaction. These results suggest that some selective sugar binding
      sites on the PGCs play a significant role in their migration, colonization and
      maturation.

PMID- 17229288
TI  - Absence of carotid rete mirabile in small tropical ruminants: implications for
      the evolution of the arterial system in artiodactyls.
AB  - The intracranial carotid rete (or rete mirabile epidurale) is a unique blood
      vascular system supplying the brain of artiodactyls, which have either an
      involuted or no internal carotid artery. Although the lesser and greater mouse
      deer (Tragulus javanicus and T. napu, respectively) are ruminants, the rete
      mirabile epidurale is absent. In these animals, as in non-artiodactyls, such as
      canines, equines and humans, the complete internal carotid artery supplies the
      brain. It is currently uncertain whether the absence of the rete is confined to
      mouse deer among ruminants. The absence of the rete in mouse deer provides new
      insights into the evolution of the arterial system in artiodactyls.

PMID- 17229289
TI  - New advances in fluorochrome sequential labelling of teeth using seven different
      fluorochromes and spectral image analysis.
AB  - Fluorochrome sequential labelling of mineralizing tissues is commonly used in
      different fields of clinical and basic research. Recently we improved polychrome
      fluorescent sequential labelling of bone by applying spectral image analysis to
      discriminate seven different fluorochromes. Although basic mineralization
      processes of bone and teeth follow comparable principles, the respective tissues
      differ in terms of matrix composition and mineral assembly. The aim of this study
      therefore was to investigate the feasibility of this new technique for polychrome
      sequential labelling of teeth and to demonstrate the advantages in the field of
      dentistry. Furthermore, the exact labelled area of each fluorochrome could be
      measured, even in regions of overlapping fluorochromes. The technique presented
      may provide a basis for further investigations of mineralization processes of
      different anatomical dental structures.

PMID- 17229297
TI  - High-density mapping of spontaneous pulmonary vein activity initiating atrial
      fibrillation in humans.
AB  - INTRODUCTION: High-density three-dimensional (3D) mapping of the pulmonary vein
      (PV)-left atrial (LA) junction was performed to characterize spontaneous PV
      activity in humans. METHODS AND RESULTS: The activation patterns of ectopic beats
      and of the initial 2 seconds of atrial fibrillation (AF) from the PVs were
      analyzed using a 64-poles basket catheter. A focal mechanism was defined as a
      discrete site of early and centrifugal activation. Continuous activity was
      considered as an activation covering > or = 80% of the tachycardia beat-to-beat
      cycle length within the mapping field. In 35 patients, 123 spontaneous focal
      ectopic beats that did not induce AF and 95 that did induce AF were mapped. The
      mean coupling interval of ectopic discharges not inducing AF was 281 +/- 70 msec
      versus 236 +/- 90 msec for ectopies initiating AF (P < or = 0.01). The first
      ectopic activity of all 218 arrhythmogenic events showed exclusively a focal
      mechanism. During the 95 episodes of AF initiation, one or two ectopic beats from
      the PVs initiated AF in the LA in 39%, a stable focal tachycardia was recorded in
      14%, continuous activity with important changes in cycle length (35 +/- 15 msec)
      suggestive of decremental or fibrillatory conduction was found in 18%, and in 29%
      the activation pattern could not be classified. No stable and sustained reentrant
      circuit could be identified by our mapping tool in the PV-LA junction.
      CONCLUSIONS: Arrhythmogenic activity from PVs in humans is predominantly due to
      discrete focal activity.

PMID- 17229290
TI  - Three-dimensional MRI perfusion maps: a step beyond volumetric analysis in mental
      disorders.
AB  - A new type of magnetic resonance imaging analysis, based on fusion of three
      dimensional reconstructions of time-to-peak parametric maps and high-resolution
      T1-weighted images, is proposed in order to evaluate the perfusion of selected
      volumes of interest. Because in recent years a wealth of data have suggested the
      crucial involvement of vascular alterations in mental diseases, we tested our new
      method on a restricted sample of schizophrenic patients and matched healthy
      controls. The perfusion of the whole brain was compared with that of the caudate
      nucleus by means of intrasubject analysis. As expected, owing to the encephalic
      vascular pattern, a significantly lower time-to-peak was observed in the caudate
      nucleus than in the whole brain in all healthy controls, indicating that the
      suggested method has enough sensitivity to detect subtle perfusion changes even
      in small volumes of interest. Interestingly, a less uniform pattern was observed
      in the schizophrenic patients. The latter finding needs to be replicated in an
      adequate number of subjects. In summary, the three-dimensional analysis method we
      propose has been shown to be a feasible tool for revealing subtle vascular
      changes both in normal subjects and in pathological conditions.

PMID- 17229298
TI  - A basket full of mechanistic insights into pulmonary vein arrhythmogenicity:
      reentry, focal activity, or fibrillatory conduction?

PMID- 17229299
TI  - Validation and clinical application of time-frequency analysis of atrial
      fibrillation electrocardiograms.
AB  - INTRODUCTION: Fibrillatory rates can reliably be obtained from surface ECGs
      during atrial fibrillation (AF) and correspond with right atrial (RA) and
      coronary sinus (CS) rates, while both the relation with pulmonary venous (PV)
      rates and determinants of fibrillatory waveform are unknown. Class III
      antiarrhythmic drugs prolong atrial refractoriness and decrease its dispersion,
      effects that may be reflected in ECG parameters. Consequently, this study sought
      (1) to investigate the relation between ECG fibrillatory rate and waveform
      characteristics with intraatrial/PV fibrillatory activity and (2) to
      noninvasively monitor class III antiarrhythmic drug effects in patients with AF.
      METHODS AND RESULTS: Thirty-six patients with drug-refractory AF who underwent
      catheter-based pulmonary vein isolation and had AF at the beginning of the
      procedure were studied. A positive correlation between V1 rates obtained by time
      frequency analysis and RA (R = 0.97, P < 0.001), CS (R = .71, P < 0.001), and PV
      rates (R = 0.65, P = 0.001) was found. Exponential decay defined as decay of the
      curve that connects power maxima of dominant and harmonic frequency components
      correlated with RA rate dispersion (R = 0.53, P = 0.004). In amiodarone-treated
      patients (n = 7), V1 rate (286 +/- 64 vs. 371 +/- 40 fpm, P < 0.001) and
      exponential decay (1.06 +/- 0.29 vs. 1.38 +/- 0.38, P = 0.034) were lower than in
      patients without amiodarone (n = 29). In 19 additional patients with persistent
      AF, oral dofetilide treatment decreased mean fibrillatory rate from 377 +/- 57 to
      294 +/- 50 fpm (P < 0.001) and exponential decay from 1.24 +/- 0.43 to 0.85 +/-
      0.22 (P = 0.002). CONCLUSIONS: Fibrillatory waves of surface ECG lead V1 closely
      reflect right atrial, and, to a lesser degree, left atrial activity. Time
      frequency analysis allows noninvasive monitoring of antiarrhythmic drug effects
      on fibrillatory rate and waveform.

PMID- 17229300
TI  - Left atrial anatomic remodeling in atrial fibrillation.

PMID- 17229301
TI  - Deterioration of organization in the first minutes of atrial fibrillation: a beat
      to-beat analysis of cycle length and wave similarity.
AB  - INTRODUCTION: It has been recently suggested that many episodes of atrial
      fibrillation (AF) may be partially organized at the onset and thus more suitable
      for antitachycardia pacing therapy. Nevertheless, the time course of organization
      in the first minutes of AF has not been quantified yet. METHODS AND RESULTS:
      Twenty episodes of paroxysmal AF were studied. Electrograms were recorded from
      the right atrium (RA), distal (CSd), and proximal coronary sinus (CSp). The time
      course of AF cycle length (AFCL) and the regularity of wave morphology
      (similarity index S) were beat-to-beat measured at each recording site during the
      first 7 minutes of AF. AFCL and S showed a decreasing trend after the onset of
      AF. AFCL decreased from 208 +/- 31 to 171 +/- 21 msec (P < 0.001), from 206 +/-
      40 to 169 +/- 23 msec (P < 0.001) and from 190 +/- 42 to 152 +/- 18 msec (P <
      0.05), respectively, in RA, CSd, and CSp. Similarly, the similarity index
      decreased in CSd from 0.37 +/- 0.27 to 0.12 +/- 0.09 (P < 0.01) and in RA from
      0.40 +/- 0.18 to 0.17 +/- 0.16 (P < 0.001). The 80% of the decrease occurred
      during the first 3 minutes of the arrhythmia, while after this time both cycle
      length and similarity index did not change significantly anymore. Conversely, the
      electrical activity in CSp was highly disorganized (S = 0.05 +/- 0.03) even in
      the first minute of AF, and no decreasing temporal trend was observed.
      CONCLUSION: Higher levels of organization and longer fibrillation intervals exist
      at the onset of AF. The degree of organization of the electrical activity decays
      within less than 3 minutes. Since antitachycardia pacing success rate increases
      with high levels of organization, these results suggest an early delivery of
      pacing treatment.

PMID- 17229303
TI  - Wrestling with post-ablation recurrence of atrial fibrillation: a question of
      weight class?

PMID- 17229304
TI  - QT interval correction in patients with cirrhosis.
AB  - INTRODUCTION: QT interval prolongation is a common electrophysiological
      abnormality in patients with cirrhosis. As QT interval varies with the heart
      rate, many QT correction formulas have been proposed, the Bazett's one being the
      most criticized because it over-corrects the QT interval and may be misleading.
      This study focused on the QT-RR relationship in patients with cirrhosis to derive
      a population-specific QT correction formula. METHODS: One hundred cirrhotic
      patients of different etiology and severity and 53 healthy controls comparable
      for age and sex were enrolled. The QT-RR relationship was analyzed in patients by
      five regression analysis models to derive the population-specific QT-RR equation.
      The QTc was calculated and compared with those calculated by four common QT
      correction formulas (Bazett, Fridericia, Framingham, and Hodges). The correlation
      coefficient QTc-RR was calculated as a measure of the independence of QTc from
      the original RR interval. RESULTS: In patients the QT-RR relationship was best
      described by the power equation "QT = 453.65 x RR1/3.02" (R2 = 0.41), similar to
      the Fridericia's formula. Bazett's formula led to the longest QTc (P < 0.0001),
      which was still significantly influenced by the RR interval (R = -0.39; P <
      0.0001), while the estimated equation led to a QTc value not influenced by RR (R
      = -0.014). CONCLUSION: Bazett's correction should be avoided in patients with
      cirrhosis because it still provides a rate-dependent QTc value and might be
      misleading, particularly when assessing the overall preoperative cardiac risk and
      the effect of drugs affecting the QT interval. In its place, our formula or that
      of Fridericia can be confidently employed.

PMID- 17229302
TI  - Organized atrial fibrillation onset: a propitious intervention window?

PMID- 17229305
TI  - Gradients of atrial refractoriness and inducibility of atrial fibrillation due to
      stimulation of ganglionated plexi.
AB  - INTRODUCTION: The mechanism(s) whereby atrial ectopy induces atrial fibrillation
      (AF) is still poorly understood. METHODS AND RESULTS: In 12 dogs, we determined
      the refractory period (RP) along the right atrium (RA) and right superior
      pulmonary vein (RSPV), and AF inducibility with and without concurrent
      stimulation of the anterior right ganglionated plexi (ARGP) at the base of the
      RSPV. Multielectrode catheters were attached to the RSPV and RA with the distal
      electrodes close to ARGP. The RP and window of vulnerability (WOV), i.e., the
      longest S1-S2 minus the shortest S1-S2 at which AF was induced, were measured
      before and during incremental levels of ARGP stimulation. Mapping of the onset of
      AF was performed using the EnSite mapping system (St. Jude Medical, St. Paul, MN,
      USA) positioned in the RA. A single premature depolarization (PD) from the RSPV
      that did not induce AF without ARGP stimulation could do so with ARGP
      stimulation. The onset of AF consistently arose at the myocardium subtending the
      ARGP. With GP stimulation, the average WOV at the RSPV-atrial junction was
      significantly wider than at the RA appendage (65 +/- 27 vs. 8 +/- 17 msec, P <
      0.05) or further along the RSPV sleeve (48 +/- 39 vs. 10 +/- 20 msec, P < 0.05).
      Even without GP stimulation, high intensity (10-20 mA) premature stimuli
      delivered at the RA appendage induced AF, originating from atrial tissue
      subtending the ARGP, presumably due to axonal conduction that activated the ARGP.
      CONCLUSION: GP stimulation, subthreshold for atrial excitation, converts isolated
      PDs into AF-inducing PDs, suggesting that autonomic tone may play a critical role
      in the initiation of paroxysmal AF.

PMID- 17229308
TI  - Common pulmonary venous ostium of the right and left inferior pulmonary veins: an
      unusual pulmonary vein anomaly depicted with 64-slice cardiac computed
      tomography.

PMID- 17229307
TI  - Percutaneous endocardial and epicardial ablation of hypotensive ventricular
      tachycardia with percutaneous left ventricular assist in the electrophysiology
      laboratory.
AB  - Ventricular tachycardia (VT) in the setting of structural heart disease is
      challenging to treat with percutaneous catheter ablation due to the presence of
      complex substrate, multiple morphologies, hemodynamic instability, and epicardial
      circuits. When substrate-based approaches fail, however, it may be impossible to
      map and ablate hemodynamically unstable arrhythmias. We describe a novel approach
      to endocardial and epicardial mapping and ablation of hypotensive VT using a
      percutaneous left ventricular assist device in the electrophysiology laboratory,
      permitting near-surgical access to cardiac structures.

PMID- 17229306
TI  - Bradykinin is a mediator, but unlikely a trigger, of antiarrhythmic effects of
      ischemic preconditioning.
AB  - OBJECTIVE: Brief reversible ischemic episodes (ischemic preconditioning, IPC)
      protect the heart against arrhythmias during a subsequent prolonged low-flow
      ischemia. We have recently shown that this protection involves release of
      bradykinin, activation of bradykinin B2 receptors followed by opening of
      sarcolemmal, but not mitochondrial ATP-sensitive K+ channels. The goal of this
      study was to clarify a trigger and/or mediator role of bradykinin in the
      antiarrhythmic effects of IPC during low-flow ischemia. METHODS: Isolated
      perfused rat hearts underwent 60 minutes of low-flow ischemia induced by reducing
      perfusion pressure followed by 60 minutes of reperfusion. Preconditioning was
      induced by 2 x 5 minutes episodes of zero-flow ischemia. In yet other groups,
      preconditioned or non-preconditioned hearts were treated either with bradykinin
      (10 nmol/L) or with HOE 140 (bradykinin B2 receptor antagonist, 100 nmol/L).
      RESULTS: IPC reduced the number of ventricular premature beats, as well as the
      incidence of ventricular tachycardia and of ventricular fibrillation during low
      flow ischemia. In addition, this protection was abolished by HOE 140 given during
      low-flow ischemia. Pharmacological preconditioning using short bradykinin
      perfusion instead of IPC did not show antiarrhythmic effects. However, bradykinin
      administered during low-flow ischemia and reperfusion reduced the number of
      ventricular premature beats and the incidence of ventricular tachycardia and of
      ventricular fibrillation during low-flow ischemia. CONCLUSION: Bradykinin is a
      mediator, but unlikely a trigger, of antiarrhythmic effects of IPC during low
      flow ischemia.

PMID- 17229310
TI  - Commotio cordis--sudden cardiac death with chest wall impact.
AB  - Commotio cordis (CC), sudden death as a result of a blunt, often innocent
      appearing chest wall blow, is being reported with increasing frequency. The
      clinical spectrum is diverse; however, a substantial number of cases occur in
      youth athletics. In events that occur during sport, victims are struck by
      projectiles regarded as standard implements of the game. Sudden death is
      instantaneous and victims are most often found in ventricular fibrillation (VF).
      Overall survival is poor; however, successful resuscitation can be achieved with
      early defibrillation. Autopsy is notable for the absence of any significant
      cardiac or thoracic injury. Development of an experimental model has allowed for
      substantial insights into the underlying mechanisms of sudden death. In
      anesthetized juvenile swine, induction of VF is instantaneous following chest
      wall blows occurring during a vulnerable window before the T wave peak. Crucial
      variables including the velocity of impact, impact location, and hardness of the
      impact object have been identified. Rapid left ventricular (LV) pressure rise
      following chest impact likely results in activation of ion channels via mechano
      electric coupling. The generation of inward current via mechano-sensitive ion
      channels likely results in augmentation of repolarization and nonuniform
      myocardial activation, and is the cause of premature ventricular depolarizations
      that are triggers of VF in CC. While softer-than-standard safety baseballs reduce
      the risk of CC, commercially available chest protectors are ineffective in
      preventing CC. The development of more effective chest protectors and more
      widespread use of automated external defibrillators at youth sporting events are
      needed.

PMID- 17229312
TI  - Cytoskeleton and vesicle mobility in astrocytes.
AB  - Exocytotic vesicles in astrocytes are increasingly viewed as essential in
      astrocyte-to-neuron communication in the brain. In neurons and excitable
      secretory cells, delivery of vesicles to the plasma membrane for exocytosis
      involves an interaction with the cytoskeleton, in particular microtubules and
      actin filaments. Whether cytoskeletal elements affect vesicle mobility in
      astrocytes is unknown. We labeled single vesicles with fluorescent atrial
      natriuretic peptide and monitored their mobility in rat astrocytes with
      depolymerized microtubules, actin, and intermediate filaments and in mouse
      astrocytes deficient in the intermediate filament proteins glial fibrillary
      acidic protein and vimentin. In astrocytes, as in neurons, microtubules
      participated in directional vesicle mobility, and actin filaments played an
      important role in this process. Depolymerization of intermediate filaments
      strongly affected vesicle trafficking and in their absence the fraction of
      vesicles with directional mobility was reduced.

PMID- 17229314
TI  - Overestimating resistance in field testing of malaria parasites: simple methods
      for estimating high EC50 values using a Bayesian approach.
AB  - Conventional methods of assessing in-vitro antimalarial drug-concentration effect
      relationships in field testing of fresh isolates assess each parasite isolate
      individually. This leads to systematic overestimation of EC50 values for the most
      resistant isolates, and thus overestimation of the degree of resistance. In
      antimalarial drug-susceptibility studies conducted on the north-western border of
      Thailand the overestimation of EC50 for the most resistant isolate ranged from
      15% for artesunate to 43% for mefloquine. If isolates cannot be stored for re
      testing, more accurate estimations of the degree of resistance can be obtained
      using a Bayesian approach to data analysis which is described here.

PMID- 17229313
TI  - Direct non-cell autonomous Pax6 activity regulates eye development in the
      zebrafish.
AB  - BACKGROUND: Modifications in Pax6 homeogene expression produce strong eye
      phenotypes. This suggested to us that eye development might be an appropriate
      model to verify if homeoprotein intercellular passage has important functions in
      early development. Similar to other homeoproteins, Pax6 has two domains that
      enable secretion and internalization by live cells and, thus, intercellular
      passage. In principle, a straightforward way to test the hypothesis would be to
      mutate one of the two sequences to produce a 'cell autonomous only' Pax6.
      However, this was not possible because these sequences are in the homeodomain and
      their modification would affect Pax6 transcriptional properties. We have thus
      developed an approach aimed at blocking Pax6 only in the extracellular milieu of
      developing zebrafish embryos. RESULTS: A first strategy was to inject a one-cell
      embryo with a mRNA encoding a secreted single-chain anti-Pax6 antibody. A second,
      complementary, strategy was to inject a Pax6 antibody in the blastula
      extracellular milieu. In both cases, 'dissymmetric eyes', 'one eye only' and 'no
      eye' phenotypes were produced. In most cases, lens phenotypes paralleled retina
      malformations. Although eye phenotypes were analyzed 30 hours post-fertilization,
      there was a strong correlation between early eye field asymmetry, early asymmetry
      in Pax6 expression and later-occurring eye malformations. Several controls were
      introduced, demonstrating that the effect is specific to Pax6 and cannot be
      explained by intracellular antibody activities. CONCLUSION: This study supports
      the hypothesis that the Pax6 transcription factor is also a signaling molecule
      with direct non-cell autonomous activity.

PMID- 17229315
TI  - Normalization of low-density microarray using external spike-in controls:
      analysis of macrophage cell lines expression profile.
AB  - BACKGROUND: The normalization of DNA microarrays allows comparison among samples
      by adjusting for individual hybridization intensities. The approaches most
      commonly used are global normalization methods that are based on the expression
      of all genes on the slide and on the modulation of a small proportion of genes.
      Alternative approaches must be developed for microarrays where the proportion of
      modulated genes and their distribution are unknown and they may be biased towards
      up- or down-modulated trends. RESULTS: The aim of the work is to study the use of
      spike-in controls to normalize low-density microarrays. Our test-array was
      designed to analyze gene modulation in response to hypoxia (a condition of low
      oxygen tension) in a macrophage cell line. RNA was extracted from controls and
      cells exposed to hypoxia, mixed with spike RNA, labeled and hybridized to our
      test-array. We used eight bacterial RNAs as source of spikes. The test-array
      contained the oligonucleotides specific for 178 mouse genes and those specific
      for the eight spikes. We assessed the quality of the spike signals, the
      reproducibility of the results and, in general, the nature of the variability.
      The small values of the coefficients of variation revealed high reproducibility
      of our platform either in replicated spots or in technical replicates. We
      demonstrated that the spike-in system was suitable for normalizing our platform
      and determining the threshold for discriminating the hypoxia modulated genes. We
      assessed the application of the spike-in normalization method to microarrays in
      which the distribution of the expression values was symmetric or asymmetric. We
      found that this system is accurate, reproducible and comparable to other
      normalization methods when the distribution of the expression values is
      symmetric. In contrast, we found that the use of the spike-in normalization
      method is superior and necessary when the distribution of the gene expression is
      asymmetric and biased towards up-regulated genes. CONCLUSION: We demonstrate that
      spike-in controls based normalization is a reliable and reproducible method that
      has the major advantage to be applicable also to biased platform where the
      distribution of the up- and down-regulated genes is asymmetric as it may occur in
      diagnostic chips.

PMID- 17229316
TI  - Neglected isolated plantar dislocation of middle cuneiform: a case report.
AB  - BACKGROUND: Four cases of plantar dislocation of middle cuneiform have been
      reported in the english literature. All of them were fresh cases and treated with
      open reduction. We are reporting a case of neglected plantar dislocation of
      middle cuneiform which was treated with excision. CASE PRESENTATION: A farmer
      presented with a painful plantar dislocation of middle cuneiform bone after 9
      months of injury. The bone was deformed and was excised by a plantar incision. It
      resulted in painless foot with no disability. CONCLUSION: The neglected plantar
      dislocated middle cuneiform bone becomes deformed due to repeated weight bearing.
      The gap gets filled with Fibrous tissue. Excision of the cuneiform gives good
      results.

PMID- 17229317
TI  - Long-term feeding ecology and habitat use in harbour porpoises Phocoena phocoena
      from Scandinavian waters inferred from trace elements and stable isotopes.
AB  - BACKGROUND: We investigated the feeding ecology and habitat use of 32 harbour
      porpoises by-caught in 4 localities along the Scandinavian coast from the North
      Sea to the Barents Sea using time-integrative markers: stable isotopes (delta13C,
      delta15N) and trace elements (Zn, Cu, Fe, Se, total Hg and Cd), in relation to
      habitat characteristics (bathymetry) and geographic position (latitude). RESULTS:
      Among the trace elements analysed, only Cd, with an oceanic specific food origin,
      was found to be useful as an ecological tracer. All other trace elements studied
      were not useful, most likely because of physiological regulation and/or few
      specific sources in the food web. The delta13C, delta15N signatures and Cd levels
      were highly correlated with each other, as well as with local bathymetry and
      geographic position (latitude). Variation in the isotopic ratios indicated a
      shift in harbour porpoise's feeding habits from pelagic prey species in deep
      northern waters to more coastal and/or demersal prey in the relatively shallow
      North Sea and Skagerrak waters. This result is consistent with stomach content
      analyses found in the literature. This shift was associated with a northward Cd
      enrichment which provides further support to the Cd 'anomaly' previously reported
      in polar waters and suggests that porpoises in deep northern waters include Cd
      contaminated prey in their diet, such as oceanic cephalopods. CONCLUSION: As
      stable isotopes and Cd provide information in the medium and the long term
      respectively, the spatial variation found, shows that harbour porpoises
      experience different ecological regimes during the year along the Scandinavian
      coasts, adapting their feeding habits to local oceanographic conditions, without
      performing extensive migration.

PMID- 17229319
TI  - Infant eye and head movements toward the side opposite the cue in the anti
      saccade paradigm.
AB  - BACKGROUND: The anti-saccade task, when people must respond in the direction
      opposite to a visual stimulus, has been used as a marker of operation of the
      frontal cortical oculomotor area. However, early development of oculomotor
      control has been little studied with the infant anti-saccade paradigm, and a few
      studies did not recognize anti-saccades in infants in light of the results of
      adult anti-saccade. Since the characteristics of infant eye movements are little
      known, applying the criteria used in adult study is by no means the best way to
      study infant anti-saccade. As it is indicated that coordinated eye and head
      movements often enable infants to control the direction of their gaze, head
      movements should be examined as an infant orienting response. The aim of this
      study was to address how infants used eye and head movements during the anti
      saccade paradigm. To distinguish infants' responses, we also investigated eye and
      head movements during a task for an inhibition of return. Inhibition of return,
      in which delayed responses occur in the direction to which attention had
      previously been oriented, has been thought to mark activity of the superior
      colliculus. Since the superior colliculus is thought to develop much earlier in
      life than the frontal lobes, we thought it useful to compare these task
      performances during infancy. METHODS: Infants were divided into three groups
      according to age. Anti-saccade and inhibition-of-return tasks were given. Their
      eye and head movements during tasks were independently recorded by the corneal
      reflection method in the head-free condition. RESULTS: Younger infants tended to
      initiate eye movement less than older ones in both tasks. In the anti-saccade
      task, responses opposite to the cue tended to show longer latency than responses
      to the cue. Infants made faster responses toward the side opposite the cue when
      it was to the right than when it was left of fixation. Regarding the comparison
      of responses toward the side opposite the cue between two tasks, the leftward eye
      movement was faster than the leftward head movements in the inhibition-of-return
      task, while no difference of latency was observed between eye and head movements
      in the anti-saccade task. A qualitative analysis of the trajectory of these
      responses revealed that head movement trajectories were steeper in the anti
      saccade than in the inhibition-of-return task. CONCLUSION: Younger infants move
      head and eyes together, with head movements frequently starting first. On the
      other hand, both the leftward latency difference between eye and head and gentle
      trajectories of head in inhibition of return indicate that eye movements are more
      predominant over head movements in the inhibition-of-return task than in the anti
      saccade task. This would suggest an earlier developing inhibition-of-return
      mechanism.

PMID- 17229320
TI  - Component retention in principal component analysis with application to cDNA
      microarray data.
AB  - Shannon entropy is used to provide an estimate of the number of interpretable
      components in a principal component analysis. In addition, several ad hoc
      stopping rules for dimension determination are reviewed and a modification of the
      broken stick model is presented. The modification incorporates a test for the
      presence of an "effective degeneracy" among the subspaces spanned by the
      eigenvectors of the correlation matrix of the data set then allocates the total
      variance among subspaces. A summary of the performance of the methods applied to
      both published microarray data sets and to simulated data is given.

PMID- 17229318
TI  - Experimental validation of novel genes predicted in the un-annotated regions of
      the Arabidopsis genome.
AB  - BACKGROUND: Several lines of evidence support the existence of novel genes and
      other transcribed units which have not yet been annotated in the Arabidopsis
      genome. Two gene prediction programs which make use of comparative genomic
      analysis, Twinscan and EuGene, have recently been deployed on the Arabidopsis
      genome. The ability of these programs to make use of sequence data from other
      species has allowed both Twinscan and EuGene to predict over 1000 genes that are
      intergenic with respect to the most recent annotation release. A high throughput
      RACE pipeline was utilized in an attempt to verify the structure and expression
      of these novel genes. RESULTS: 1,071 un-annotated loci were targeted by RACE, and
      full length sequence coverage was obtained for 35% of the targeted genes. We have
      verified the structure and expression of 378 genes that were not present within
      the most recent release of the Arabidopsis genome annotation. These 378 genes
      represent a structurally diverse set of transcripts and encode a functionally
      diverse set of proteins. CONCLUSION: We have investigated the accuracy of the
      Twinscan and EuGene gene prediction programs and found them to be reliable
      predictors of gene structure in Arabidopsis. Several hundred previously un
      annotated genes were validated by this work. Based upon this information derived
      from these efforts it is likely that the Arabidopsis genome annotation continues
      to overlook several hundred protein coding genes.

PMID- 17229321
TI  - Need telomere maintenance? Call 911.
AB  - "Natura non facit saltum" (nature makes no leap) the Latins used to say, meaning
      that nature does not like discontinuities. Cells make no exception and indeed any
      discontinuity in the DNA double helix is promptly detected, triggering an
      alteration of cell proliferation and an attempt to repair. Yet, linear
      chromosomes bear DNA ends that are compatible with normal cell proliferation and
      they escape, under normal conditions, any repair. How telomeres, the chromosomes
      tips, achieve that is not fully understood. We recently observed that the
      Rad9/Hus1/Rad1 (911) complex, previously known for its functions in DNA
      metabolism and DNA damage responses, is constitutively associated with telomeres
      and plays an important role in their maintenance. Here, we summarize the
      available data and discuss the potential mechanisms of 911 action at telomeres.

PMID- 17229323
TI  - Body Mass Index, percent body fat, and regional body fat distribution in relation
      to leptin concentrations in healthy, non-smoking postmenopausal women in a
      feeding study.
AB  - BACKGROUND: The relationship between BMI and leptin has been studied extensively
      in the past, but previous reports in postmenopausal women have not been conducted
      under carefully controlled dietary conditions of weight maintenance using precise
      measures of body fat distribution. The aim of the present study was to examine
      the association between serum leptin concentration and adiposity as estimated by
      BMI and dual energy x-ray absorptiometry (DEXA) measures (percent body fat,
      central and peripheral fat, and lean mass) in postmenopausal women. METHODS: This
      study was conducted as a cross-sectional analysis within the control segment of a
      randomized, crossover trial in which postmenopausal women (n = 51) consumed 0
      (control), 15 (one drink), and 30 (two drinks) g alcohol (ethanol)/d for 8 weeks
      as part of a controlled diet. BMIs were determined and DEXA scans were
      administered to the women during the 0 g alcohol treatment, and a blood sample
      was collected at baseline and week 8 of each study period for leptin analysis.
      RESULTS AND DISCUSSION: In multivariate analysis, women who were overweight (BMI
      > 25 to < or = 30 kg/m2) had a 2-fold increase, and obese women (BMI > 30 kg/m2)
      had more than a 3-fold increase in serum leptin concentrations compared to normal
      weight (BMI < or =25 kg/m2) women. When the models for the different measures of
      adiposity were assessed by multiple R2, models which included percent body fat
      explained the highest proportion (approximately 80%) of the serum leptin
      variance. CONCLUSION: Under carefully controlled dietary conditions, we confirm
      that higher levels of adiposity were associated with higher concentrations of
      serum leptin. It appears that percent body fat in postmenopausal women may be the
      best adiposity-related predictor of serum leptin.

PMID- 17229322
TI  - Severe paraneoplastic hypoglycemia in a patient with a gastrointestinal stromal
      tumor with an exon 9 mutation: a case report.
AB  - BACKGROUND: Non-islet cell tumor induced hypoglycemia (NICTH) is a very rare
      phenomenon, but even more so in gastrointestinal stromal tumors. It tends to
      present in large or metastatic tumors, and can appear at any time in the
      progression of the disease. We present herein a case of NICTH in a GIST tumor and
      report an exon 9 mutation associated to it. CASE PRESENTATION: A thirty nine year
      old man with a recurrent, metastatic gastrointestinal stromal tumor presented to
      the hospital with nausea, dizziness, loss of consciousness, and profound
      hypoglycemia (20 mg/dL). There was no evidence of factitious hypoglycemia. He was
      stabilized with a continuous glucose infusion and following selective vascular
      embolization, the patient underwent debulking of a multicentric 40 cm x 25 cm x
      10 cm gastrointestinal stromal tumor. After resection, the patient became
      euglycemic and returned to his normal activities. Tumor analysis confirmed
      excessive production of insulin-like growth factor II m-RNA and the precursor
      protein, "big" insulin-like growth factor II. Mutational analysis also identified
      a rare, 6 bp tandem repeat insert (gcctat) at position 1530 in exon 9 of KIT.
      CONCLUSION: Optimal management of gastrointestinal stromal tumor-induced
      hypoglycemia requires a multidisciplinary approach, and surgical debulking is the
      treatment of choice to obtain immediate symptom relief. Imatinib or combinations
      of glucocorticoids and growth hormone are alternative palliative strategies for
      symptomatic hypoglycemia. In addition, mutations in exon 9 of the tyrosine kinase
      receptor KIT occur in 11-20% of GIST and are often associated with poor patient
      outcomes. The association of this KIT mutation with non-islet cell tumor induced
      hypoglycemia has yet to be established.

PMID- 17229325
TI  - Long-term effects of the Mediterranean lifestyle program: a randomized clinical
      trial for postmenopausal women with type 2 diabetes.
AB  - BACKGROUND: Multiple-risk-factor interventions offer a promising means for
      addressing the complex interactions between lifestyle behaviors, psychosocial
      factors, and the social environment. This report examines the long-term effects
      of a multiple-risk-factor intervention. METHODS: Postmenopausal women (N = 279)
      with type 2 diabetes participated in the Mediterranean Lifestyle Program (MLP), a
      randomized, comprehensive lifestyle intervention study. The intervention targeted
      healthful eating, physical activity, stress management, smoking cessation, and
      social support. Outcomes included lifestyle behaviors (i.e., dietary intake,
      physical activity, stress management, smoking cessation), psychosocial variables
      (e.g., social support, problem solving, self-efficacy, depression, quality of
      life), and cost analyses at baseline, and 6, 12, and 24 months. RESULTS: MLP
      participants showed significant 12- and 24-month improvements in all targeted
      lifestyle behaviors with one exception (there were too few smokers to analyze
      tobacco use effects), and in psychosocial measures of use of supportive
      resources, problem solving, self-efficacy, and quality of life. CONCLUSION: The
      MLP was more effective than usual care over 24 months in producing improvements
      on behavioral and psychosocial outcomes. Directions for future research include
      replication with other populations.

PMID- 17229324
TI  - Prevention, control, and elimination of neglected diseases in the Americas:
      pathways to integrated, inter-programmatic, inter-sectoral action for health and
      development.
AB  - BACKGROUND: In the Latin America and Caribbean region over 210 million people
      live below the poverty line. These impoverished and marginalized populations are
      heavily burdened with neglected communicable diseases. These diseases continue to
      enact a toll, not only on families and communities, but on the economically
      constrained countries themselves. DISCUSSION: As national public health
      priorities, neglected communicable diseases typically maintain a low profile and
      are often left out when public health agendas are formulated. While many of the
      neglected diseases do not directly cause high rates of mortality, they contribute
      to an enormous rate of morbidity and a drastic reduction in income for the most
      poverty-stricken families and communities. The persistence of this "vicious
      cycle" between poverty and poor health demonstrates the importance of linking the
      activities of the health sector with those of other sectors such as education,
      housing, water and sanitation, labor, public works, transportation, agriculture,
      industry, and economic development. SUMMARY: The purpose of this paper is three
      fold. First, it focuses on a need for integrated "pro-poor" approaches and
      policies to be developed in order to more adequately address the multi-faceted
      nature of neglected diseases. This represents a move away from traditional
      disease-centered approaches to a holistic approach that looks at the overarching
      causes and mechanisms that influence the health and well being of communities.
      The second objective of the paper outlines the need for a specific strategy for
      addressing these diseases and offers several programmatic entry points in the
      context of broad public health measures involving multiple sectors. Finally, the
      paper presents several current Pan American Health Organization and other
      institutional initiatives that already document the importance of integrated,
      inter-programmatic, and inter-sectoral approaches. They provide the framework for
      a renewed effort toward the efficient use of resources and the development of a
      comprehensive integrated solution to neglected communicable diseases found in the
      context of poverty, and tailored to the needs of local communities.

PMID- 17229326
TI  - "Pseudosarcoma" in a pregnant woman.
AB  - BACKGROUND: Intravascular fasciitis (IVF) is a rare benign condition
      characterised by reactive myofibroblastic proliferation arising from the
      superficial or deep fascia and involving arteries and/or veins. It is a distinct
      variant of the more common condition of nodular fasciitis, which possesses
      similar clinical and histological features to IVF, but lacks vascular invasion. A
      thorough review of the literature revealed 26 reported cases of IVF. CASE
      PRESENTATION: We report a case of IVF in a 16-week pregnant lady affecting the
      hypothenar eminence of the hand associated with the ulnar artery. CONCLUSION: The
      characteristic involvement of muscular arteries and veins by reactive
      myofibroblastic proliferation in IVF suggests a malignant component and often
      leads to an inappropriate diagnosis for this benign condition. We propose that
      hormone-related changes associated with pregnancy may play an important role in
      the aetiopathogenesis of this myofibroblastic lesion.

PMID- 17229327
TI  - Memorable Medical Mentors: XVII Isidor C. Rubin (1883-1958).

PMID- 17229328
TI  - Clinical significance of proteinuria in pregnancy.
AB  - Urinary protein excretion is considered abnormal in pregnant women when it
      exceeds 300 mg/24 hours at anytime during gestation, a level that usually
      correlates with 1+ on urine dipstick. Proteinuria documented before pregnancy or
      before 20 weeks' gestation suggests preexisting renal disease. The National High
      Blood Pressure Education Program Working Group recommended that that the
      diagnosis of proteinuria be based on the 24-hour urine collection. Preeclampsia
      is the leading diagnosis that must be excluded in all women with proteinuria
      first identified after 20 weeks of gestation. Given the vasospastic nature of
      this condition, when it is present, the degree of proteinuria may fluctuate
      widely from hour-to-hour. Hypertension or proteinuria may be absent in 10-15% of
      patients with HELLP syndrome and in 38% of patients with eclampsia. The acute
      onset of proteinuria and worsening hypertension in women with chronic
      hypertension is suggestive of superimposed preeclampsia, which increases adverse
      outcomes. However, because proteinuria is not independently predictive of adverse
      outcome, an exclusive proteinuric criterion as an indication for preterm delivery
      in preeclampsia should be discouraged. TARGET AUDIENCE: Obstetricians &
      Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this
      article, the reader should be able to state that measurement of urinary protein
      levels by simple techniques are not sensitive or specific, recall that both
      hypertension and proteinuria may be absent in patients with preeclampsia, and
      explain that proteinuria is not predictive of adverse outcomes and that delivery
      should not be based on protein excretion alone.

PMID- 17229329
TI  - Gestational diabetes: a review of the current literature and guidelines.
AB  - Despite large numbers of original research studies spanning 4 decades there is
      still no consensus on the subject of gestational diabetes. Should all pregnant
      women be screened or only those with risk factors? Or is it safe not to screen at
      all? Which screening test and which diagnostic test are the most reliable? Which
      cutoff values should we use? What are the risks involved for mother and baby and
      can treatment improve outcome? What is the connection between gestational
      diabetes and diabetes mellitus type II? Are there disadvantages to screening? A
      review of relevant articles shows that definitive answers to these questions are
      not yet available. There is no gold standard screening test and no threshold
      glucose value above which complications are markedly increased. On the contrary,
      there appears to be a continuum of slowly increasing risks with rising blood
      glucose values, where it seems difficult to draw a clear line between pathology
      and physiology. Moreover, treatment has thus far not been shown to significantly
      improve outcome. There seems to be an indistinct area between the diagnosis of
      gestational diabetes and diabetes mellitus type II, where women with risk factors
      for one are also predisposed to develop the other, thereby confusing the
      diagnosis. Finally, the disadvantages to diagnosing and treating women without a
      clearly proven benefit seem to be significant. Therefore it seems defensible to
      suspend all screening and treatment for gestational diabetes, or at least
      significantly raise the threshold for making a positive diagnosis and initiating
      treatment, until further research has proven a clear benefit. TARGET AUDIENCE:
      Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After
      completion of this article, the reader should be able to summarize that there is
      still no worldwide consensus on the diagnosis, management, and adverse effects of
      Gestational Diabetes Mellitus (GDM); explain that all methods of screening vary
      in sensitivity and depend on very strict preparations for screening; state that
      there is no agreement on ideal levels of blood glucose to prevent untoward
      effects; and recall that there are two very large prospective studies that
      clarify the dark waters and that we should await their results.

PMID- 17229330
TI  - The antiretrovirals in pregnancy registry: a fifteenth anniversary celebration.
AB  - The year 2007 marks the fifteenth anniversary year of the founding of a landmark
      effort in drug safety risk management, the formation of the first monitoring
      effort of an antiretroviral (ARV) drug in pregnancy which has become the
      Antiretrovirals in Pregnancy Registry, the APR. This multicompany, multi-national
      voluntary collaborative registry monitors pregnancy exposure to a class of highly
      important drugs for any indication of an increase in the postexposure incidence
      of birth defects in the offspring of these pregnancies. To recognize the
      anniversary, the Steering Committee of the APR has commissioned this review of
      the contributions and lessons learned over the past decade and a half and, in the
      spirit of continuous process improvement, has committed to apply these lessons
      for the next fifteen years. This retrospective examines the antecedents to this
      registry and the context in which the APR was formed; the early efforts to
      establish technical and organizational procedures and policies; the evolving
      experiences with enrollment and follow-up, patient and participant protections,
      information management and oversight; public and regulatory dissemination; and of
      course, the accomplishments and lessons learned. TARGET AUDIENCE: Obstetricians &
      Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this
      article, the reader should be able to explain the value of a drug registry in
      determining safety risk management; summarize that the Antiretroviral (ARV) drugs
      in Pregnancy Registry (APR) is a very successful multinational, multicompany
      collaborative effort that has been in place for 15 years; and state that it has
      been an ideal public interest effort dealing with the devastating pandemic of
      human immunodeficiency viral disease.

PMID- 17229331
TI  - Meeting highlights 6th International Congress on monoclonal antibodies in cancer,
      August 2006, Washington, DC.

PMID- 17229332
TI  - Systemic immunoglobulin light-chain amyloidosis.
AB  - Amyloidosis is a rare disease in which amyloid fibrils compromise organ function
      and lead to death. Systemic immunoglobulin light-chain amyloidosis, usually
      caused by free light chains (FLCs) made by clonal plasma cells, is the most
      frequent type. Hereditary and senile systemic amyloidosis are less frequent
      types. Rarely, a patient with a tissue diagnosis of amyloidosis might have a
      monoclonal gammopathy and a hereditary protein. In systemic immunoglobulin light
      chain amyloidosis, circulating clonal light chains can be measured with the FLC
      assay and provide a target for therapy aimed at eliminating the underlying plasma
      cell disorder while supporting the patient. Elimination of the pathologic FLC can
      lead to resorption of amyloid deposits and improvement in organ function. Monthly
      oral melphalan and dexamethasone for 1 year is effective therapy for patients not
      eligible for autologous stem cell transplantation (SCT) but carries a risk of
      myelodysplasia. For patients with limited organ involvement, SCT is an effective
      approach and, when followed after SCT by adjuvant thalidomide and dexamethasone
      for persistent plasma cell disease, achieves a high 1-year hematologic response
      rate. Complete hematologic responses can be durable beyond a decade and are
      usually associated with organ recovery. New agents, such as bortezomib and
      lenalidomide, have shown promising activity, and novel monoclonal antibody
      approaches are also under active investigation.

PMID- 17229333
TI  - Use of single nucleotide polymorphism-based mapping arrays to detect copy number
      changes and loss of heterozygosity in multiple myeloma.
AB  - The genetics of multiple myeloma is a vastly studied field in which techniques
      such as classical cytogenetics, fluorescence in situ hybridization, and
      comparative genomic hybridization have been used. More recently, single
      nucleotide polymorphism (SNP)-based mapping arrays have become available that
      allow the identification of regions of gain or loss as small as 2.5 kb. In
      addition to the increased resolution of SNP-based arrays, the detection of loss
      of heterozygosity is also possible. This allows the identification of loss of
      heterozygosity regions that arise through monosomy and recombination, resulting
      in uniparental disomy, which cannot be detected by conventional genetic methods.
      In this review, we discuss the benefits of SNP-based arrays along with some of
      the drawbacks and how that data can be used in conjunction with expression data
      to identify genes with altered expression in regions of interest.

PMID- 17229334
TI  - Arsenic compounds in the treatment of multiple myeloma: a new role for a
      historical remedy.
AB  - Arsenic compounds have been used since ancient times to treat a wide variety of
      ailments. Although the use of arsenic to treat hematologic cancers has been
      documented since the 19th century, widespread use of arsenic compounds in
      patients with hematologic malignancies did not occur until the 1990s, when
      several groups in China reported impressive clinical response rates in patients
      with acute promyelocytic leukemia who had received arsenic trioxide.
      Subsequently, clinical studies conducted in the United States confirmed earlier
      reports, and arsenic trioxide was approved by the Food and Drug Administration
      for the treatment of relapsed/refractory acute promyelocytic leukemia. The use of
      arsenic compounds in the treatment of multiple myeloma (MM) is supported by the
      proposed mechanisms of action underlying the antitumor activity of arsenic and by
      preclinical studies showing antiproliferative and cytotoxic activities in cell
      culture and animal models. Moreover, clinical studies of arsenic compounds,
      particularly arsenic trioxide-based regimens, have shown that this drug is
      clinically active in patients with relapsed/refractory MM. Combination studies
      with other antimyeloma agents have shown evidence of synergy with arsenic
      trioxide. Furthermore, arsenic trioxide-based regimens in MM appear to be well
      tolerated, particularly with regard to cardiac toxicity. The activity and
      tolerability observed in clinical studies promise to make arsenic-based
      chemotherapy a viable treatment option for patients whose disease does not
      respond to or who cannot tolerate other chemotherapy regimens.

PMID- 17229335
TI  - Biologic correlates of response and survival in patients with cutaneous T-cell
      lymphoma treated with denileukin diftitox.
AB  - BACKGROUND: Denileukin diftitox, a fusion protein consisting of peptide sequences
      for the enzymatically active and membrane translocation domains of diphtheria
      toxin and human interleukin, resulted in a response rate of 30% in the phase III
      registration trial in patients with recurrent or persistent cutaneous T-cell
      lymphoma (CTCL). Little is known with regard to the biologic correlates of
      response or the impact of denileukin diftitox on disease progression and
      survival. PATIENTS AND METHODS: In our single-center series of 37 patients with
      early- and advanced-stage disease with CTCL treated with denileukin diftitox at a
      dose of 9 microg/kg or 18 microg/kg per day, we observed an overall response rate
      of 51%. RESULTS: In 8 patients with early-stage (< IIA) CTCL, there were 5
      responses (62.5%), and the median survival has not been reached, with 70% of
      patients still alive at 46 months. In 29 patients with advanced-stage (>/= IIB)
      disease, there were 14 responses (49.3%), and the median survival was 31 months.
      Changes in the number of CD4+ CD25+ T-cell populations were observed in 7 of 19
      responders, with no overall changes in the absolute lymphocyte counts during the
      course of therapy. Decrease in lactate dehydrogenase was strongly correlated with
      clinical response (P < 0.05). CONCLUSION: Denilekin diftitox was a well-tolerated
      treatment in early- and advanced-stage CTCL and was not associated with
      detrimental immunologic efects on lymphocyte populations.

PMID- 17229336
TI  - Prognostic value of serum beta2-microglobulin in patients with Waldenstrom's
      macroglobulinemia requiring treatment.
AB  - PURPOSE: Waldenstrom's macroglobulinemia (WM) is a lymphoplasmacytoid lymphoma
      characterized by a relatively indolent course with median survival ranging from 5
      years to 10 years in different series. Several clinical and laboratory variables
      have been associated with inferior survival, such as advanced age,
      hyperviscosity, presence of cytopenia, and hypoalbuminemia. Recent data indicate
      that serum 2-microglobulin (2M) might also be significant. The purpose of our
      study was to assess possible correlations of 2M with clinical and laboratory
      variables and to further evaluate its association with cause-specific and overall
      survival (OS) of patients with WM requiring treatment. PATIENTS AND METHODS: We
      analyzed 124 patients with WM with an available pretreatment value of 2M. Median
      age was 70 years (range, 28-89 years), and median survival was 105 months.
      Multiple clinical and laboratory parameters were evaluated for their possible
      correlation with OS. RESULTS: Patients with older age, anemia, thrombocytopenia,
      hypoalbuminemia, and higher creatinine levels had significantly greater serum 2M
      levels. This variable was associated with impaired cause-specific survival and OS
      in the whole group of patients and in patients aged </= 70 years. More
      specifically, OS for all patients according to serum 2M > 4 mg/dL versus </= 4
      mg/dL was 79 months versus 115 months (P = 0.01). CONCLUSION: Our data provide
      further evidence that high 2M levels are an important parameter associated with
      inferior OS and cause-specific survival of patients with WM requiring treatment.
      This parameter may be used to stratify patients involved in prospective clinical
      trials.

PMID- 17229337
TI  - Phase I trial of first-line bortezomib/thalidomide plus chemotherapy for
      induction and stem cell mobilization in patients with multiple myeloma.
AB  - BACKGROUND: In preclinical studies, bortezomib was shown to suppress tumor
      growth, sensitize malignant cells to apoptosis, and reverse chemotherapy
      resistance. PATIENTS AND METHODS: We evaluated the addition of escalating doses
      of bortezomib 0.7, 1, and 1.3 mg/m2 intravenously on days 1, 4, and 8 to DT-PACE
      (cisplatin 10 mg/m2, doxorubicin 10 mg/m2, cyclophosphamide 400 mg/m2, and
      etoposide 40 mg/m2 per day by intravenous continuous infusion on days 1-4) plus
      oral dexamethasone 40 mg on days 1-4 and thalidomide 200 mg on days 1-8 in newly
      diagnosed patients with multiple myeloma. Peripheral blood stem cells were
      collected after cycle 1. Twelve patients completed the study, and all received
      autologous stem cell transplantation (SCT). RESULTS: Hematologic toxicities were
      predictable, with 3 episodes of neutropenic fever. Grade >/= 2 nonhematologic
      toxicities included diarrhea (n = 1), deep vein thrombosis (n = 2), hypotension
      (n = 2), syncope (n = 1), and peripheral neuropathy (n = 3). The median number of
      CD34+ cells collected was 20.57 x 10 superset6 CD34+ cells/kg. After 2 cycles, 10
      of 12 patients exhibited a partial response or better. Best response after
      autologous SCT, complete response/near complete response was exhibited in 9
      patients, and partial response was exhibited in 3 patients. At a median of 20
      months, 4 patients experienced relapse and 1 had died. Bortezomib/DT-PACE
      compared favorably with DT-PACE with regard to leukapheresis days, total CD34+
      cell collection, and engraftment. CONCLUSION: This novel strategy of simultaneous
      proteasome inhibition in combination with thalidomide and chemotherapy was
      effective and safe, allowing for adequate stem cell collection and early
      autologous SCT; its impact on overall survival, especially in patients with high
      risk myeloma, awaits further investigation.

PMID- 17229338
TI  - Prognostic impact of pretransplantation computed tomography and gallium scans in
      patients with Hodgkin lymphoma with poor prognosis undergoing hematopoietic stem
      cell transplantation.
AB  - BACKGROUND: The present study evaluated computed tomography (CT) and Gallium-67
      scanning (67Ga) before transplantation as prognostic factors for overall survival
      (OS) and event-free survival (EFS) in patients with relapsed or primary
      refractory Hodgkin lymphoma undergoing high-dose chemotherapy and stem cell
      transplantation. PATIENTS AND METHODS: Forty-five patients were included. Of
      these, 10 (22%) had positive CT and 67Ga scan results, 21 (47%) had negative
      results of both techniques, 12 (27%) had positive CT/negative 67Ga scan results,
      and 2 (5%) had negative CT/positive 67Ga scan results. RESULTS: Patients with
      positive CT/67Ga scan results had a significantly worse EFS and OS at 5 years
      than those with negative 67Ga scan results, whether it was associated with
      positive or negative CT scan results (0 and 25% vs. 83% and 90% vs. 74% and 83%,
      respectively; P < 0.001). With a median follow-up of 59 months (range, 6-150
      months), no differences were observed between patients with negative CT/67Ga scan
      results and those with positive CT/negative 67Ga scan results, with an EFS and OS
      at 5 years of 74% vs. 83% and 83% vs. 90%, respectively. In multivariate
      analysis, the presence of pretransplantation positive CT/67Ga scan results
      adversely influenced EFS and OS (hazard ratio, 39; 95% confidence interval, 8-202
      [P < 0.001] and hazard ratio, 24; 95% confidence interval, 4-135 [P < 0.001],
      respectively). CONCLUSION: Gallium-67 scans help to identify pretransplantation
      CT-positive patients with a different outcome. A group of patients with positive
      CT/negative 67Ga scan results before transplantation who showed a favorable
      outcome with a low rate of relapse and another group of patients with positive
      CT/67Ga scan results before transplantation who showed poor prognosis did not
      benefit from autologous stem cell transplantation. They should be offered other
      therapeutic strategies.

PMID- 17229339
TI  - High clinical response rate with multimodality immunomodulatory therapy for
      Sezary syndrome.
AB  - PURPOSE: The goal of this study was to evaluate the clinical response rate of
      patients with Sezary syndrome (SS) to multimodality immunomodulatory therapy
      consisting of extracorporeal photopheresis in combination with >/= 2 systemic
      biologic response modifiers (interferon-, interferon-, retinoids, and/or
      sargramostim) and psoralen plus UV-A. PATIENTS AND METHODS: Twenty-eight patients
      who met established criteria for SS were treated with multimodality
      immunomodulatory therapy at the Hospital of the University of Pennsylvania
      between January 2000 and December 2002. All patients received > 6 cycles of
      extracorporeal photopheresis. Patients were categorized into groups based on
      their response to therapy. RESULTS: An overall clinical response of 89% was
      achieved with multimodality immunomodulatory therapy. Twenty-nine percent of
      patients exhibited a complete response, characterized by no evidence of cutaneous
      disease and a Sezary count 5%. Sixty-one percent exhibited a partial response.
      Eleven percent were nonresponders. CONCLUSION: Based on our experience,
      multimodality immunomodulatory therapy is an exceptionally effective treatment
      for SS. The durability of response and impact on overall survival remains to be
      determined; however, this approach offers an appealing alternative to treatments
      associated with higher morbidity rates.

PMID- 17229340
TI  - Bortezomib-induced tumor lysis syndrome in multiple myeloma.
AB  - Tumor lysis syndrome (TLS) is exceedingly rare in multiple myeloma because of the
      relatively slow proliferation and response of the malignant cells. Bortezomib is
      a novel agent that inhibits proteasome and has shown activity against multiple
      myeloma. We report 8 episodes of TLS seen in 7 patients with bortezomib therapy,
      with or without dexamethasone, among 496 patients treated on 3 phase II
      multicenter studies. Biochemical abnormalities resolved with supportive therapy
      in 6 patients (including hemodialysis in 2) but proved fatal in 1. Clinicians
      should be alert for TLS in patients with myeloma with significant disease burden
      treated with bortezomib because of the potential for rapid onset of cell lysis
      with this agent.

PMID- 17229341
TI  - Case report of a patient with primary central nervous system lymphoma treated
      with radioimmunotherapy.
AB  - Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin
      lymphoma arising within and confined to the central nervous system and, unlike
      other primary brain tumors, is very responsive to treatment. Aggressive
      management can lead to prolonged remissions or cures. However, the prognosis at
      relapse is generally poor with limited therapeutic options; clearly, new
      strategies are needed for these patients. Radioimmunotherapy has a growing role
      in the management of systemic non-Hodgkin lymphoma but has not been evaluated in
      PCNSL. We report here the first patient with PCNSL treated with
      radioimmunotherapy.

PMID- 17229342
TI  - Subcutaneous panniculitis lymphoma: erythema nodosum-like.
AB  - We report the case of a patient who presented with painful nodular subcutaneous
      lesions on the lower limbs and episodes of high temperature (> 39.5 degrees C).
      Histologic examination and immunohistochemical study of a biopsy specimen from a
      nodular lesion were consistent with the diagnosis of subcutaneous panniculitis
      like T-cell lymphoma, a rare form of non-Hodgkin lymphoma. Diagnosis is made
      particularly difficult, especially in the early stages, by nonspecific clinical
      features shared by many types of panniculitis. Therefore, it seems advisable to
      consider the possibility of this type of lymphoma in all cases of panniculitis
      and to perform careful and continuous follow-up of all cases in which a clear
      diagnosis is not formulated at the outset, with regular repetition of skin
      biopsies at appropriate intervals.

PMID- 17229343
TI  - Distribution and property of nerve fibers in human long bone tissue.
AB  - OBJECTIVE: To observe the distribution of the nerve fibers in the bone tissue and
      the entry points of these fibers into the bone. METHODS: The adult tibia was used
      for the ground sections which were afterwards made into the slice sections by
      decalcification in ethylenediamine tetraacetic acid (EDTA). The ground sections
      were stained in silver and the slice sections were stained in silver and
      haematoxylin and eosin (HE) respectively. Then, the samples of the transmission
      electron microscope and the atomic force microscope were made and observed.
      RESULTS: In the human long bone tissue, many nerve fibers were distributed in the
      membrane, cortical bone, cancellous bone and marrow. The nerve fibers entered the
      bone from the nutrient foramen, and passed through the nutrient canal,
      Haversian's canal and Volkmann's canal, and finally into the bone marrow. In the
      nutrient canal, the nerve fibers, mainly the medullary nerve fibers, followed the
      blood vessel into the bone. In the cortical bone, the nerve fibers also followed
      the blood vessels and were mainly distributed along Haversian's canal and
      Volkmann's canal. In the bone trabecular and bone marrow, there were many nerve
      fiber endings arranged around the blood vessels, mainly around the tunica media
      of medium-size arteries in the marrow and around capillary blood vessels, and a
      few scattered in the bone marrow. There were sporadic nerve endings in epiphyseal
      plate and no nerve fibers permeated epiphysis to diaphysis. No distribution of
      nerve fibers could be found in cartilaginous part. CONCLUSIONS: There are many
      nerve fibers in bone and the nerve passageway is nutrient foramen, Volkman's
      canal, Haversian's canal and bone marrow.

PMID- 17229344
TI  - Green fluorescent protein as marker in chondrocytes overexpressing human insulin
      like growth factor-1 for repair of articular cartilage defects in rabbits.
AB  - OBJECTIVE: To label the primary articular chondrocytes overexpressing human
      insulin-like growth factor (hIGF 1) with green fluorescent protein (GFP) for
      repair of articular cartilage defects in rabbits. METHODS: GFP cDNA was inserted
      into pcDNA3.1 hIGF 1 to label the expression vector. The recombinant vector,
      pcGI, a mammalian expression vector with multiple cloning sites under two
      respective cytomegalovirus promoters/enhancers, was transfected into the primary
      articular chondrocytes with the help of lipofectamine. After the positive cell
      clones were selected by G418, G418-resistant chondrocytes were cultured in medium
      for 4 weeks. The stable expression of hIGF 1 in the articular chondrocytes was
      determined by in situ hybridization and immunocytochemical analysis and the GFP
      was confirmed under a fluorescence microscope. Methyl thiazolyl tetrazolium (MTT)
      and flow cytometer methods were employed to determine the effect of transfection
      on proliferation of chondrocytes. Gray value was used to analyze quantitatively
      the expression of type II collagen. RESULTS: The expression of hIGF 1 and GFP was
      confirmed in transfected chondrocytes by in situ hybridization,
      immunocytochemical analysis and fluorescence microscope observation. Green
      articular chondrocytes overexpressing hIGF 1 could expand and maintain their
      chondrogenic phenotypes for more than 4 weeks. After the transfection of IGF 1,
      the proliferation of chondrocytes was enhanced and the chondrocytes could
      effectively maintain the expression of type II collagen. CONCLUSIONS: The hIGF 1
      eukaryotic expression vector containing GFP marker gene has been successfully
      constructed. GFP, which can be visualized in real time and in situ, is stably
      expressed in articular chondrocytes overexpressing hIGF 1. The labeled articular
      chondrocytes overexpressing hIGF 1 can be applied in cell-mediated gene therapy
      as well as for other biomedical purposes of transgenic chondrocytes.

PMID- 17229345
TI  - Application of spiral CT image 3D reconstruction in severe talar neck fracture.
AB  - OBJECTIVE: To explore the application of the spiral computerized tomography (CT)
      image three-dimensional (3D) reconstruction technique associated with the
      conventional radiography in the diagnosis and treatment of severe talar neck
      fracture. METHODS: Using the multi-slice spiral CT image 3D reconstruction
      technique, we analysed 11 cases of talar neck fracture. The fractures were
      reduced and fixed through a minimal incision and internal fixation with titanium
      cannulated lag screws. RESULTS: In the 11 cases, the results of CT image 3D
      reconstruction were in concordance with plain radiograph in 6 case of Hawkins
      type II. And the remaining 5 cases of Hawkins types III and IV could not be
      classified exactly only by radiographs, one of whom was misdiagnosed. After using
      the CT image 3D reconstruction, the 5 cases were classified exactly before
      osteosynthesis. The classifications of these 11 cases were confirmed finally by
      surgical findings. The duration of operation were 45-140 min, averaging 81 min
      (including the duration of C-arm fluoroscopy). X-ray exposure time was 6-58
      seconds, averaging 22 seconds. The blood loss was less than 100 ml. The fracture
      union was achieved in 3 months. No nonunion, talus avascular necrosis or joint
      surface collapse occurred. Postoperative follow-up was from 1 to 25 months.
      According to Hawkins score, excellent result was found in 6 type II cases and 1
      type III case; good result in 1 type III case with both medial and lateral
      malleolar fracture, 1 type III with medial malleolus fractures and 1 open type
      III; fair result in 1 open type IV with lateral malleolus fracture. CONCLUSIONS:
      By using the multi-slice spiral CT image 3D reconstruction associated with
      radiography to diagnose and treat severe talar neck fractures, the accuracy of
      diagnosis can be improved obviously. Based on this technique, more consummate
      operational plan can be designed and performed so as to achieve a better
      therapeutic effect.

PMID- 17229346
TI  - Arthroscopic single-bundle reconstruction of posterior cruciate ligament with
      quadrupled hamstring tendon.
AB  - OBJECTIVE: To evaluate the technique and outcome of arthroscopic single-bundle
      reconstruction of posterior cruciate ligament (PCL) with quadrupled hamstring
      tendon. METHODS: From April 2001 to October 2004, 49 knees with PCL tears in 49
      patients were verified with arthroscope in this department. Of them, 13 were
      combined with anterior cruciate ligament tears, 14 with disruptions of the
      posterolateral corner, 6 with ruptures of the posteromedial corner and medial
      collateral ligament, 9 with lateral meniscus tears, 5 with medial meniscus tears
      and 2 with popliteal vascular tears. All the damaged PCLs were reconstructed with
      single-bundle of autogenous quadrupled hamstring tendons under arthroscope.
      Biodegradable interference screws or blunt titanium interference screws were used
      for direct anatomic fixation of the reconstructed ligament. RESULTS: After
      operation, no severe complications occurred at early stage in the 49 patients.
      All of them were followed up for 10-52 months with an average of 22.0 months+/
      10.7 months. Lysholm score was remarkably improved from 30-60 (mean: 47.96+/
      8.16) preoperatively to 70-95 (mean: 89.08+/-6.10) at the last postoperative
      follow-up (P less than 0.01). Furthermore, there was a significant improvement in
      International Knee Documentation Committee (IKDC) score from abnormal (Grade C)
      in 10 knees and severely abnormal (Grade D) in 39 preoperatively to normal (Grade
      A) in 20, nearly normal (Grade B) in 24 and abnormal in 5 at the last follow-up.
      Of the 49 patients, 40 returned to the same activity level as before and 9 were
      under the level. CONCLUSIONS: Single-bundle reconstruction of PCL with quadrupled
      hamstring tendons has the advantage of minimal trauma in surgery and satisfactory
      outcome.

PMID- 17229348
TI  - Vertebral plate regeneration induced by radiation-sterilized allogeneic bone
      sheets in sheep.
AB  - OBJECTIVE: To evaluate the effects and mechanism of radiation-sterilized
      allogeneic bone sheets in inducing vertebral plate regeneration after laminectomy
      in sheep. METHODS: Twelve adult male sheep (aged 1.5 years and weighing 27 kg on
      average) provided by China Institute for Radiation Protection underwent L3-4 and
      L4-5 laminectomy. Then they were randomly divided into two groups: Group A (n=6)
      and Group B (n=6). The operated sites of L4-5 in Group A and L3-4 in Group B were
      covered by "H-shaped" freeze-drying and radiation-sterilized allogeneic bone
      sheets (the experimental segments), while the operated sites of L3-4 in Group A
      and L4-5 in Group B were uncovered as the self controls (the control segments).
      The regeneration process of the vertebral plate and the adhesion degree of the
      dura were observed at 4, 8, 12, 16, 20 and 24 weeks after operation. X-ray and CT
      scan were performed in both segments of L3-4 and L4-5 at 4 and 24 weeks after
      operation. RESULTS: In the experimental segments, the bone sheets were located in
      the anatomical site of vertebral plate, and no lumbar spinal stenosis or
      compression of the dura was observed. The bone sheets were absorbed gradually and
      fused well with the regenerated vertebral plate. While in the control segments,
      the regeneration of vertebral plate was not completed yet, the scar was inserted
      into the spinal canal, compressing the dura and the spinal cord, and the epidural
      area almost disappeared. Compared with the control segments, the dura adhesion
      degree in the experimental regenerated segments was much milder (P less than
      0.01), the internal volume of the vertebral canal had no obvious change and the
      shape of the dura sack remained well without obvious compression. CONCLUSIONS:
      Freeze-drying and radiation-sterilized allogeneic bone sheets are ideal materials
      for extradural laminoplasty due to their good biocompatibility, biomechanical
      characteristics and osteogenic ability. They can effectively reduce formation of
      post-laminectomy scars, prevent recurrence of post-laminectomy spinal stenosis,
      and induce regeneration of vertebral plates.

PMID- 17229347
TI  - Diagnostic value of CTA and MRA in intracranial traumatic aneurysms.
AB  - OBJECTIVE: To investigate the diagnostic value of computerized tomographic
      angiography (CTA) and magnetic resonance angiography (MRA) for intracranial
      traumatic aneurysms (TAs). METHODS: CTA and MRA of six patients with intracranial
      TAs verified by digital subtraction angiography (DSA) and surgery were
      retrospectively analysed. All patients were examined by nonenhanced computerized
      tomography (CT) and two by CTA. The source data were reconstructed by volume
      rendering (VR) and multi-planar reconstruction (MPR) from CTA. Four of them had
      maximum intensity project (MIP) from MRA. RESULTS: Of the six patients, a total
      of seven TAs were detected by CTA and MRA examinations. Five cases had only one
      TA and one case had two TAs. The average diameter was 2.3 cm (1.1-3.3 cm). CTA
      demonstrated two TAs appeared at the cavernous segment of the internal carotid
      artery (ICA) and the middle cerebral artery (MCA) respectively. MCA TA was
      definitely and clearly demonstrated on VR images, whereas VR images failed to
      depict the cavernous ICA TA, which was detected on MPR images. Two TAs were found
      irregular saccular shape, irregular margin of parent artery and wide neck on CTA.
      Four MRA examinations demonstrated five TAs, including the cavernous segment ICA
      TAs (2 cases), the supraclinoid segment ICA TA (1 case), and the cavernous
      segment associated with opposite side of the petrosal segment ICA TA (1 case). In
      a cavernous ICA TA, MRA only revealed aneurysm body, whereas aneurysm neck and
      distal segment of the parent artery were not revealed. In the remaining cases,
      MRA clearly depicted aneurysm body and parent artery, whereas the neck was not
      displayed. ICA TAs showed irregular capsule-like high signal intensity on MRA
      images. Four TAs exhibited irregular distal segment of the parent artery. TAs at
      the supraclinoid segment or MCA failed to find fracture signs on nonenhanced CT.
      CONCLUSIONS: Both CTA and MRA examinations are the effective non-invasive method
      of imageology for diagnosing intracranial TAs, while CTA is more eligible for
      diagnosing TAs after nonenhanced CT has demonstrated skull base fractures.

PMID- 17229349
TI  - Comparison of therapeutic effect between percutaneous kyphoplasty and pedicle
      screw system on vertebral compression fracture.
AB  - OBJECTIVE: To compare the clinical efficacy of percutaneous kyphoplasty (PKP)
      with pedicle screw system (PS) in the treatment of vertebral compression
      fracture(VCF). METHODS: Eighty-six patients with VCF were treated either by PKP
      (Group A, n equal to 30) or PS (Group B, n equal to 56). The anterior,
      intermediate, and posterior heights of the vertebrae body, visual analogue pain
      scale (VAS) before and after operation, the duration of operation, and amount of
      blood loss between two groups were compared. RESULTS: No statistical difference
      was noted regarding the vertebral height between two groups. Significant
      difference was seen in VAS, duration of operation and amount of blood loss
      between the two groups (P less than 0.01). CONCLUSIONS: Percutaneous kyphoplasty
      has the similar therapeutic efficacy with pedicle screw system in treatment of
      VCF with a minimal invasion, less operation time and blood loss. For those with
      posterior wall destruction, PS is deemed favorable.

PMID- 17229350
TI  - Finite element analysis of impact loads on the femur.
AB  - OBJECTIVE: To investigate the stress distribution and fracture mechanism of
      proximal femur under impact loads. METHODS: The image data of one male's femur
      were collected by the Lightspeed multi-lay spiral computed tomography. A 3D
      finite element model of the femur was established by employing the finite element
      software ANSYS, which mainly concentrated on the effects of the directions of the
      impact loads arising from intense movements and the parenchyma on the hip joint
      as well as those of the femur material properties on the distribution of the
      Mises equivalent stress in the femur after impact. RESULTS: The numerical results
      about the effects of the angle sigma of the impact loads to the anterior
      direction and the angle gamma of the impact loads to the femur shaft on the bone
      fracture were given. The angle sigma had larger effect on the stress distribution
      than the angle gamma, which mainly represented the fracture of the upper femur
      including the femoral neck fracture when the posterolateral femur was impacted.
      This result was consistent with the clinical one. The parenchyma on the hip joint
      has relatively large relaxation effect on the impact loads. CONCLUSIONS: A 3D
      finite element analysis model of the femoral hip joint under dynamic loads is
      successfully established by using the impact dynamic theory.

PMID- 17229351
TI  - Delayed release particles from vascular endothelial growth factor for repairing
      spinal cord ischemic injury of rats.
AB  - OBJECTIVE: To study the effect of delayed release particles from vascular
      endothelial growth factor (VEGF) on the reparation of ischemic injury of spinal
      cord in rats. METHODS: The spinal cord ischemia model of rats was established.
      The delayed release particles from VEGF were injected via the intubation of
      spinal subarachnoid space. The rehabilitation was observed by the assessment of
      unfold claw reflection, space between toes, spinal evoked potential (SEP) and
      motor evoked potential (MEP). RESULTS: VEGF prompted SEP and MEP appearance,
      improved the motor function of hind limbs. CONCLUSIONS: VEGF can promote the
      rehabilitation of spinal cord ischemic injury of rats.

PMID- 17229352
TI  - Analysis on care outcome of patients with polytrauma and coma.
AB  - OBJECTIVE: To make further improvement of outcome of patients with polytrauma and
      coma. METHODS: The data of 3361 patients (2378 males and 983 females, aged from 5
      95 years, 38.2 years on average) with severe polytrauma and coma admitted to
      Chongqing Emergency Medical Center (Level I Trauma Center), Chongqing, China,
      from November 1978 to December 2004 were analyzed retrospectively in this study.
      RESULTS: The overall survival rate and mortality were 93.2% (3133/3361) and 6.8%
      (228/3361), respectively. The mortalities in patients with coma duration less
      than 1 hour and combined with neural dysfunction and in patients with coma
      duration larger than or equal to 1 hour and combined with or without neural
      dysfunction were significantly higher than that of those with coma duration less
      than 1 hour but without neural dysfunction [39.5% (136/344) vs 3.0% (92/3017), P
      less than 0.01]. There existed significant differences in GCS, ISS, and revised
      trauma score (RTS) between the death group and the survival group (P less than
      0.01). RTS was in good correspondence with patient's pathophysiological status
      and outcome in patients with multiple trauma and coma for different groups of
      systolic blood pressure (SBP). The mortality in patients with SBP less than 90 mm
      Hg was significantly higher than that of those with SBP larger than or equal to
      90 mm Hg [33.3% (68/204) vs 5.1% (160/3157), P less than 0.01]. The mortality in
      polytrauma patients combined with serious head injury (AIS larger than or equal
      to 3) was 8.2%, among which, 76.5% died from lung complications. The morbidity
      rate of lung complications and mortality rate increased in patients with head
      injury complicated with chest or abdomen injury (23.9%, 61.1% vs 27.3%, 50.0%).
      The mortality reached up to 61.9% in patients complicated with severe head, chest
      and abdomen injuries simultaneously. CONCLUSIONS: It plays a key role to
      establish a fast and effective trauma care system and prompt and definite
      surgical procedures and to strengthen the management of complications for
      improving the survival rate of patients with severe polytrauma and coma.

PMID- 17229353
TI  - Preparation and physicochemical properties of scaffold materials of heterogeneous
      deproteinized bone.
AB  - OBJECTIVE: To prepare and observe the physicochemical properties of scaffold
      materials of heterogeneous deproteinized tissue-engineered bone. METHODS:
      Deproteinized bone was made through a series of physicochemical treatments in pig
      ribs and analyzed with histological observation, scanning electron microscopy,
      infrared spectrum, X-ray diffraction and energy dispersive analysis, Kjeldahl
      determination and mechanics analysis. RESULTS: Interstitial collagen fiber was
      positive and mucin was negative in deproteinized bone, but, both were positive in
      fresh bone. Deproteinized bone maintained natural pore network. Its pore size was
      472.51 micromolar+/-7.02 micromolar and the porosity was 78.15%+/-6.45%. The
      results of infrared spectrum showed that collagen was present in deproteinized
      bone. Both fresh and deproteinized bone had curve of hydroxyapatite. The Ca/P
      ratios were 1.71+/-0.95 and 1.68+/-0.76 (P larger than 0.05), and the protein
      contents were 26.6%+/-2.23% and 19.1%+/-2.14% (P less than 0.05) in fresh and
      deproteinized bone, respectively. There was no significant difference of
      destruction load under compression and maximal destruction load between fresh and
      deproteinized bone (P larger than 0.05). The elastic modulus was higher in
      deproteinized bone than that in fresh bone (P less than 0.05). CONCLUSIONS:
      Physicochemical properties and mechanic strength of deproteinized tissue
      engineered bone meet the demands of ideal scaffold materials. But, its
      immunogenicity should be observed through further experiments for its clinical
      applications.

PMID- 17229354
TI  - Emergency endovascular repair of iliac artery rupture caused by post-stenting
      angioplasty with an endograft.
AB  - Iliac artery rupture is a rare complication of post-stenting angioplasty and can
      lead to massive life-threatening haemorrhage. Conventional surgery can not repair
      the damaged vessel easily and may cause substantial blood loss and high operative
      morbidity and mortality. We report our experience with a self-expanding covered
      endoprosthesis for endovascular repair of the rupture of an iliac artery caused
      by stenting angioplasty.

PMID- 17229359
TI  - Response of rural physicians in a non-fee-for-service environment to acute
      increases in demand due to physician shortages.
AB  - INTRODUCTION: The Weeneebayko Health Ahtuskaywin (WHA) is an Aboriginal regional
      health authority serving a large remote region on the west coast of James Bay.
      The physicians are all paid on a non-fee-for-service basis. There are periods of
      acute shortage, periods of relative stability and periods when much of the care
      is provided by locum physicians. As a closed system, it is ideal for the
      investigation of physician response to periods of acute increases in demand for
      service. PURPOSE: This study investigated the relationships between staffing
      levels and service provision to describe the response of physicians to increased
      demand due to an acute shortage of physicians. It also looked at whether payment
      options affected these relationships. METHODS: Using an existing administrative
      database from WHA for the period 1999 to 2002, relationships between staffing
      levels and service provision were investigated. We looked at the relationship
      between total physician levels and the number of patients seen per family
      medicine clinic. We also studied the relationships between total physician
      staffing levels and the number of patients seen in clinic, in the emergency
      department (ED), and per ED shift. We also looked at some proxy measures for the
      level of intensity of the work, including the number of hospital inpatients, the
      number of medevacs per ED shift and the number of ED shifts per physician.
      Exploratory graphical analysis was conducted and was followed by linear
      regression for associations of interest. RESULTS AND CONCLUSION: During periods
      of decreased staffing, physicians saw more patients per clinic and ED shift,
      despite the lack of financial incentives. The study also clearly demonstrates the
      increased intensity of the workloads carried by rural physicians in times of
      staffing shortages as noted by increased numbers of ED shifts, increased numbers
      of medevacs per ED shift and the lack of a decline in inpatient numbers. This
      highlights the need for ongoing recruitment and retention efforts in rural and
      remote locations to ensure adequate physician staffing levels, if burnout is to
      be avoided.

PMID- 17229360
TI  - Survey of rural family physician-obstetricians in Southwestern Ontario.
AB  - INTRODUCTION: The objectives of this paper are 1) to analyze the characteristics
      of rural physicians who currently practise obstetrics, their training background
      and the environment in which they work and 2) to develop strategies to sustain
      rural obstetrical services. METHODS: Information was gathered using both a survey
      and brief individual interviews. PARTICIPANTS: A survey was sent to 56 family
      physicians who currently practise obstetrics,as well as those who had stopped
      within the past 2 years, in the Southwestern Ontario communities of Clinton,
      Goderich, Hanover, Kincardine, Markdale, Mount Forest, Palmerston, Walkerton,
      Wiarton and Wingham. RESULTS: Forty-four physicians responded to the survey.
      Results indicate that current obstetrical training programs are lacking in the
      following areas: the provision of positive role models/mentors, rural placements,
      experience in complex decision-making, and instilling confidence in graduates.
      Physicians appear to be internally motivated to practise obstetrics, claiming it
      is important to their professional goals and personal values. Support systems of
      colleagues, nursing staff, administration, family and friends, were identified as
      vital components of a successful obstetrical program. CONCLUSION: Educators are
      advised to identify students with an internal motivation to practise rural
      obstetrics early in their medical training and provide them with mentors, rural
      placements, confidence and experience in complex decision-making.

PMID- 17229361
TI  - Shared geriatric mental health care in a rural community.
AB  - INTRODUCTION: A pilot project in shared mental health care was initiated to
      explore opportunities to increase the capacity of the rural primary care system
      as a resource for older people with mental health needs. This was done within a
      framework for the delivery of best practices in geriatric mental health outreach.
      METHODS: Shared-care strategies combining education and clinical consultation
      between mentor psychiatrists and family physicians were implemented and then
      evaluated after one year to identify key factors in the success of approaches to
      shared mental health care for older people in a rural setting. RESULTS: Results
      provided new insights into shared care between primary care and specialty
      geriatric mental health services, rural geriatric mental health service delivery,
      developmental phases in service learning approaches, and building knowledge
      networks to promote continuing best practices. CONCLUSION: The results from the
      project's process evaluation have been integrated into the development of a
      permanent shared geriatric mental health care service for the rural setting.
      Preparation for an outcome evaluation that will focus on the impact on patient
      care has also been initiated.

PMID- 17229362
TI  - Telehealth and the recruitment and retention of physicians in rural and remote
      regions: a Delphi study.
AB  - INTRODUCTION: The availability of a medical workforce is a growing concern for
      rural and remote communities across Canada. In the last decade, various
      telehealth experiences have highlighted the potential impact of this technology
      on professional as well as organizational practices. But could telehealth be a
      strategy to attract and maintain physicians in rural and remote communities? The
      objective of this study was to identify a reliable list of recruitment and
      retention factors on which telehealth could have an impact. METHODS: We conducted
      2 literature reviews and a Delphi study among 12 telehealth experts across
      Canada. RESULTS: The literature reviews identified 7 categories of recruitment
      and retention factors on which telehealth could have an impact: 1) individual, 2)
      familial, 3) contextual, 4) professional, 5) organizational, 6) educational, and
      7) economic. CONCLUSIONS: Experts consulted through the Delphi study reached
      consensus on 31 out of 34 of the proposed statements about the impact of
      telehealth. This consensus can now be used as a conceptual model for further
      studies on the topic.

PMID- 17229364
TI  - Country cardiograms case 32: Paroxysmal atrial tachycardia with 2:1 block.

PMID- 17229363
TI  - The occasional shoulder dystocia.

PMID- 17229366
TI  - Setting up your ideal rural elective.

PMID- 17229368
TI  - [Value of brain natriuretic peptide in the diagnosis of pediatric heart failure].

PMID- 17229369
TI  - [Updated knowledge about the mechanism of heart failure].

PMID- 17229370
TI  - [Diagnostic value of the currently used criteria and brain natriuretic peptide
      for diagnosing congestive heart failure in children with congenital heart
      disease].
AB  - OBJECTIVE: To improve the accuracy of diagnosis of heart failure (HF) has been
      the focus of research for a long time. The diagnosis for HF with congenital heart
      disease, however, is more difficult. The aim of the study was to evaluate the
      diagnostic criteria for HF in children and examine the value of plasma brain
      natriuretic peptide (BNP) and NT-proBNP for diagnosing HF in pediatric patients
      with congenital heart disease, and to look for the most valuable index for the
      diagnosis according to the multifactor analysis. METHODS: Totally 118 children
      with congenital heart disease were enrolled. They were diagnosed using modified
      Ross score, Qingdao criteria, NYU PHFI, and plasma BNP and NT-proBNP. According
      to modified Ross score as the referent criteria, other diagnostic criteria and
      plasma BNP and NT-proBNP were studied. The sensitivity, specificity and area of
      the ROC curve were examined. Logistic regression analysis was used to select the
      valuable index for diagnosing HF. RESULTS: (1) The value of each clinical
      criteria: 1 The sensitivity of Qingdao criteria for diagnosing HF was 47.9%. The
      specificity was 100% and the accuracy was 57.6%. 2 There were 52 patients younger
      than six months in whom 27 (51.9%) were breast fed. Only 25 children were
      measured with Ross score. The Ross score was positively correlated with the
      modified Ross score (r = 0.948). The area under the ROC curve of Ross score
      diagnosing HF was 0.985, and the sensitivity was 88%, while the specificity was
      100%. 3 NYU PHFI score was positively correlated with the modified Ross score.
      The area under the ROC curve of the NYU PHFI diagnosing HF was 0.964, and the sum
      of sensitivity and specificity was favorite when > or = 8 was set as the cut-off
      point. If > 2 was set as cut-off point, it had a high sensitivity but a low
      specificity. The sensitivity of NYU PHFI was 100% > was set 2 as cut-point for
      diagnosing HF, but the specificity was 4.5%. (2) Plasma BNP and NT-proBNP were
      positively correlated with the modified Ross score, and increased with the
      severity of congestive HF. The area under the ROC curve of BNP was 0.880, and the
      cut-off line was > or = 349 pg/ml. The area under the ROC curve of NT-proBNP was
      0.981, and the cut-off line was > or = 499 fmol/ml. (3) Logistic regression
      analysis showed that in multifactor analysis, only plasma concentration of NT
      proBNP, dyspnea, tachycardia, tachypnea, failure to thrive were the independent
      predictors for diagnosing HF. (4) Plasma concentration of NT-proBNP incorporated
      with clinical criteria would improve its accuracy. CONCLUSION: All the clinical
      criteria commonly used were valuable for diagnosing HF in children with
      congenital heart disease, but each has its own limits, such as the low
      sensitivity of Qingdao, the low adaptation of Ross score because of the high
      breast-feeding rate in our country and the low specificity of NYU PHFI when > 2
      was set as the cut-off point. Plasma concentrations of BNP and NT-proBNP were
      valuable for diagnosing HF in children with congenital heart disease, and NT
      proBNP was the independent predictor for HF.

PMID- 17229371
TI  - [Expression of connective tissue growth factor in cardiomyocyte of young rats
      with heart failure and benazepril intervention].
AB  - OBJECTIVES: Ventricular remodeling is an important pathologic progress in almost
      all end stage heart failure (HF), and it is characterized by ventricular
      thickening and cardiac fibrosis with poor prognosis. The connective tissue growth
      factor (CTGF), a new growth factor with multi-function, has an important role in
      fibrosis of tissue and organs. It has been demonstrated that angiotensin
      converting enzyme inhibitor (ACEI) can prevent the development of cardiomyocyte
      from remodeling and improve cardiac function. Researchers try to test the
      hypothesis that cardiac function improvement attributable to ACEI is associated
      with inhibiting expression of CTGF in patients with HF. The aim of this study was
      to observe changes in CTGF expression in cardiomyocyte of young rats with HF and
      effect of benazepril on CTGF. METHODS: The animal model of HF was established by
      constriction of abdominal aorta. Five weeks old rats were randomly divided into 3
      groups after 6 weeks of operation: (1) HF group without treatment (n = 15); (2)
      HF group where rats were treated with benazepril (n = 15); (3) sham-operated
      group (n = 15) where rats were administered benazepril through direct gastric
      gavage. After 4 weeks of treatment, the high frequency ultrasound was performed.
      The expression of CTGF was detected by immunohistochemistry and semi-quantative
      reverse transcription-polymerase chain reaction. RESULTS: Compared with the sham
      operated group, left ventricular diastolic dimension (LVEDD), left ventricular
      systolic dimension (LVESD), interventricular septal thickness at end-diastole
      (IVSTd), interventricular septal thickness at end-systole (IVSTs), left
      ventricular posterior wall thickness at end-diastole (LVPWTd), left ventricular
      posterior wall thickness at end-systole (LVPWTs), left ventricular relative
      weight (LVRW), and right ventricular relative weight (RVRW) were all increased (P
      < 0.01), but ejection fraction (EF) and fractional shortening (FS) were decreased
      (P < 0.01). CTGF positive cells and expression of CTGF mRNA (0.609 +/- 0.065 vs
      0.117 +/- 0.011, P < 0.01) were increased in HF group without treatment. LVESD,
      IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were all decreased (P < 0.01), but FS
      and EF were increased (P < 0.01) in cases of HF treated with benazepril when
      compared with HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs,
      LVRW and RVRW were higher (P < 0.01), EF and FS were lower (P < 0.01), CTGF
      positive cells and expression of CTGF mRNA were higher (P < 0.01) in HF group
      treated with benazepril than those of sham-operated group. CONCLUSION: The
      expression of CTGF was increased in the cardiomyocyte of young rats with HF and
      benazepril could prevent left ventricular from remodeling partly and improve
      cardiac function by inhibiting the expression of CTGF in cardiomyocyte in cases
      of HF.

PMID- 17229374
TI  - [Clinical significance of brain natriuretic peptide measurements].

PMID- 17229373
TI  - [A study on atrioventricular annular movement in healthy children by tissue
      Doppler imaging].
AB  - OBJECTIVE: Detecting the atrioventricular annular velocity along the long axis of
      ventricle by tissue Doppler imaging (TDI) is a useful modality to quantitatively
      assess global myocardial function. The present study was designed to
      quantitatively assess ventricular function in healthy children by TDI and to
      evaluate the clinical effect of growth and echocardiographic parameters on TDI
      velocities during childhood. METHODS: The study enrolled 242 healthy children
      aged 3 days to 17 years and they were divided into 8 groups: < 1 month of age
      group (37 cases), 1 month-of age group (28 cases), 7 months-of age group (21
      cases), 1 year-of age group (36 cases), 4 years-of age group (40 cases), 7 years
      of age group (26 cases), 10 years-of age group (28 cases) and > or = 13 years of
      age group (26 cases). Pulsed wave TDI velocities were obtained at the lateral
      mitral annulus (MA-L), basal septum (MA-S) and lateral tricuspid annulus (TA)
      during ventricular systole (Sa), early diastole (Ea) and late diastole (Aa), and
      Ea/Aa and E/Ea were obtained. Conventional echocardiography performed done and
      the parameters of left ventricular end-diastolic dimension (LVEDD), left
      ventricular ejection fraction (LVEF), the transmitral and transtricuspid flow E
      wave and A wave velocities and E/A ratio were obtained. TDI parameters were
      compared with demographic and echocardiographic variables. RESULTS: Sa, Ea and
      Ea/Aa were the lowest in children < 1 month of age [MA-L: Sa (4.8 +/- 0.7) cm/s,
      Ea (6.6 +/- 1.1) cm/s; MA-S: Sa (4.1 +/- 0.6) cm/s, Ea (5.0 +/- 0.8) cm/s; TA: Sa
      (6.2 +/- 1.2) cm/s, Ea (6.4 +/- 1.0) cm/s], and increased with age. The increase
      was significant from 1 month- to 1 year-of age group 1 year-of age group: MA-L:
      Sa (8.5 +/- 2.0) cm/s, Ea (16.3 +/- 2.6) cm/s; MA-S: Sa (7.2 +/- 0.8) cm/s, Ea
      (12.2 +/- 1.6) cm/s; TA: Sa (12.6 +/- 2.3) cm/s, Ea (14.7 +/- 2.6) cm/s. Ea and
      Sa of TA reached the older children's value earlier than those of the mitral
      annulus did. Aa increased in the 1 month-of age group compared to < 1 month of
      age group and remained stable beyond 1 year-of age group. Mitral annulus E/Ea
      ratio was high among neonates to 7-months-old children (MA-L: 9.2 +/- 2.1, MA-S:
      12.1 +/- 2.9), and decreased with age, and there was a significant decrease in 1
      year-of age group (MA-L: 5.9 +/- 1.2, MA-S: 7.8 +/- 1.3). In these healthy
      children, all the above TDI parameters except Aa were influenced by age, body
      surface area (BSA), LVEDD and heart rate. The influence of age and BSA showed a
      logarithm model. LVEDD was the main factor that influenced Sa and Ea of MA-L and
      MA-S, and it was the only single factor that influenced E/Ea ratio at mitral
      annulus. CONCLUSIONS: This study demonstrated that the left and right ventricular
      function developed with age in childhood, and it developed most rapidly during
      infancy and toddler period. The right ventricular function matured earlier than
      that of the left ventricle. Cardiac growth, age, and heart rate had important
      clinical effects on TDI velocities during childhood, and LVEDD had the most
      important influence on left ventricular systolic and diastolic function.

PMID- 17229375
TI  - [Advance in the treatment of heart failure in children].

PMID- 17229376
TI  - [Advance in the therapy for fetal congenital heart disease].

PMID- 17229378
TI  - [Guideline of diagnosis and treatment for heart failure in children].

PMID- 17229377
TI  - [Progress in photosensitive epilepsy].

PMID- 17229379
TI  - [Two cases of myiasis cutis in children].

PMID- 17229380
TI  - [Diagnosis and treatment for attention-deficit/hyperactivity disorder in
      children].

PMID- 17229381
TI  - [Relationship between the genotype and hematologic characteristics in the fetuses
      with thalassemia].
AB  - OBJECTIVES: To investigate the relationship between the genotype and the
      hematologic characteristics in the fetuses with different types of thalassemia.
      METHODS: Fetal blood samples were taken by cordocentesis, and hemograms from 572
      fetuses at the gestational age of 18 to 38 weeks were examined. According to the
      genotypes of thalassemia, there were 117 fetuses with heterozygous alpha
      thalassemia-1, and 60 with homozygous alpha-thalassemia-1. Twenty had beta
      thalassemia mild, and 9 had beta-thalassemia major, respectively. The
      hematological parameters in these groups were compared with reference group in
      which 366 cases were included. RESULTS: In alpha-thalassemia groups, hemoglobin
      (Hb), hematocrit (HCT), mean cell volume (MCV), mean cell hemoglobin (MCH), and
      mean cell hemoglobin concentration (MCHC) significantly decreased (P < 0.001),
      but in heterozygous alpha-thalassemia-1, red blood cell (RBC) increased. In
      homozygous alpha-thalassemia-1, RBC decreased significantly (P < 0.001), but
      white blood cell and nucleated erythrocyte increased (P < 0.001). There were no
      significant differences between beta-thalassemia and reference group in most
      hematological parameters except for decrease of MCHC. CONCLUSIONS: In the fetal
      period, the hemogram of the fetuses with alpha-thalassemia changes significantly,
      while it does not change in beta-thalassemia. For the couple with heterozygous
      alpha-thalassemia, hemogram can provide some information for prenatal screening
      and diagnosis for those fetuses with alpha-thalassemia, especially for
      homozygous, but genotype detection is necessary for confirming the diagnosis.

PMID- 17229382
TI  - [Fetal echocardiography in diagnosing congenital heart disease prenatally: a
      multicenter clinical study].
AB  - OBJECTIVE: To evaluate the detection and accuracy of fetal echocardiography for
      congenital heart defects among high-risk populations. METHODS: A prospective
      observational study of prenatal diagnosis of congenital heart disease was
      conducted in two tertiary obstetrics and gynecology hospitals between January
      2003 and December 2004. Consecutive fetuses at risk of congenital heart disease
      underwent detailed fetal echocardiography during the study period. B-mode and
      colour/pulsed Doppler flow imaging were used in all cases. Follow-up was sought
      for all pregnancies. Indications for referral, maternal and gestational age at
      diagnosis, as well as prenatal and postnatal diagnosis were recorded
      prospectively. By comparing prenatal and postnatal diagnoses, sensitivity,
      specificity, and predictive values were estimated. RESULTS: A series of 2063 high
      risk fetuses underwent detailed fetal echocardiography during the study period.
      The mean gestational age at examination was 26.5 weeks, ranging from 16 to 42
      weeks. The most common indications for fetal echocardiography were advanced
      maternal age (31.7%), fetal arrhythmias (13.5%) and maternal infections (10.4%).
      Forty-three cases of fetal congenital heart disease were detected. The mean
      gestational age at prenatal diagnosis was 27.3 weeks ranging from 16 to 40 weeks.
      There were 3 false-negatives and 1 false-positive. The sensitivity, specificity,
      positive and negative predictive values were 92.1%, 99.9%, 97.2%, and 99.8%,
      respectively. Diagnostic accuracy was 86.1%. A cardiac defect suspected on
      routine prenatal sonography accounted for the highest proportion of abnormal
      cases (67.4%). As for pregnancy outcome, there were 24 (52.1%) terminations; 2.2%
      died in utero, 13% postnatally, and 28.3% survived. CONCLUSIONS: (1) Fetal
      congenital heart disease can be identified reliably by prenatal echocardiography.
      (2) Possible congenital heart disease or suspected heart defect noted on a
      screening obstetric sonogram is an important indication for fetal
      echocardiography. (3) A sequential segmental approach is critical for correct
      evaluation of the cardiac malformation. (4) The outcome of the patients with
      congenital heart disease is poor and a multidisciplinary approach is needed to
      the parental counseling and perinatal management planning.

PMID- 17229383
TI  - [Comprehensive protocol for diagnosis and treatment of childhood neuroblastoma-
      results of 45 cases].
AB  - OBJECTIVE: The aim of the paper was to improve the prognosis of neuroblastoma
      (NB) stage III and IV in children through the comprehensive therapy including
      chemotherapy, delayed tumor resection, autologous stem cell transplantation
      (ASCT) and inducing differentiation and to analyze the factors affecting the
      prognosis. METHODS: Newly diagnosed neuroblastoma patients seen from Oct.1998 to
      Dec.2003 were divided into high, medium and low risk groups depending on clinical
      stage and age. Comprehensive protocol included accurate staging, delayed and/or
      second tumor resection for stage III and IV patients, chemotherapy of different
      intensity mainly composed of cell cycle nonspecific drugs and 13-cis-retinoid for
      inducing cell differentiation. ASCT was given at the end of therapy for high risk
      group. RESULT: Forty-five patients, 6 months to 11 years of age, 32 males and 13
      females, were analyzed. Of them, 15 were found to have the tumor in adrenal
      gland, 12 had the tumor extended to the retro-peritoneal space, while in 15 cases
      the tumor was beside the spinal column in chest and in 3 the tumor was located in
      other places. Nine cases had stage I, 1 case had stage II, 8 cases had III, 26
      cases had stage IV and 1 case had stage IVs of the tumor. Depending on the age
      and stage of the tumor, 26 cases were aligned into high risk protocol, 10 into
      medium risk and 9 into low risk groups. Thirty nine cases were treated as
      planned. Eleven of them received ASCT including 2 cases who received second ASCT.
      Of the thirty-nine patients, 31 achieved complete remission (CR) and 8 partial
      remission (PR) after surgery and/or chemotherapy. During up to 21 months median
      following up period (range 14 to 64 months), 24 cases (62%) kept CR (median 22
      months) and 4 survived with stable disease. The survival rate (SR) was 72%.
      Eleven cases died of relapse and disease progression. No death occurred from
      treatment complication. Statistical analysis showed that the age older than 18
      months, and stage III and IV of the tumor were the factors predicting poor
      prognosis (P = 0.04 and 0.003, respectively). Patients who had the tumor
      originated from the retroperitoneal space, who had incomplete tumor resection,
      and those who did not receive ASCT had poorer prognosis, but the differences were
      not significant (P = 0.092, 0.55 and 0.60, respectively). CONCLUSION: The
      comprehensive protocol seemed to be reasonable. Age older than 18 months, and
      stage III and IV were the factors suggesting poor prognosis. The origin of the
      tumor, completeness of tumor resection, and use of ASCT had no significant impact
      on the prognosis.

PMID- 17229384
TI  - [Expression of gastrin, somatostatin, PCNA and Fas-L in the mucosa of gastric
      antrum of children with chronic gastritis and duodenal ulcer].
AB  - OBJECTIVE: Since application of pediatric gastroscopy in the mid-nineteen
      nineties, there has been a trend that the prevalence rates of pediatric gastritis
      and duodenal ulcer (DU) are increasing. The diagnosed rate of pediatric gastritis
      has accounted for 85% - 95% of the total number of children who received
      gastroscopy, and the rate of DU accounted for 8% - 22%. Such a high rates of the
      diseases may influence the development of the children severely. However, the
      etiology and pathogenesis of pediatric chronic gastritis and DU have not been
      completely elucidated. The disordered gastrointestinal hormones play a crucial
      role in the pediatric chronic gastritis and DU. This study focused on the
      expression of gastrin (GAS), somatostatin (SS) in the mucosa of gastric antrum
      and PCNA and Fas-L in the sinus ventriculi and their possible roles in the
      pathogenesis of pediatric chronic gastritis and DU. METHOD: The sinus ventriculi
      mucosal samples of 83 cases were collected via gastroscopic biopsy from the
      hospital during the recent two years and the cases were divided into five groups:
      group A, chronic superficial gastritis, Helicobacter pylori (Hp)(+); group B,
      chronic superficial gastritis, Hp(-); group C, DU, Hp(+); Group D, DU, Hp(-);
      Group E, normal sinus ventriculi mucosa, Hp(-). Immunohistochemical staining (En
      Vision) was carried out for GAS, SS, PCNA and Fas-L, and positive cells of each
      slide were counted (x 400). Statistically significant differences among groups
      for continuous data were assessed with the software SPSS10.0. RESULTS: The
      expressions of GAS and SS in the groups A through E had no significant
      difference. The expression of PCNA in group A was significantly higher than that
      in group B (P < 0.05), and no significant differences were found among the other
      groups. There were no significant differences in expressions of Fas-L among the
      five groups. CONCLUSION: There seems to be an increasing tendency in the
      expressions of GAS and SS in children with chronic gastritis and duodenal ulcer.
      Hp infection promotes the multiplication of the sinus ventriculi mucosal
      epithelium cells in the pediatric chronic gastritis.

PMID- 17229385
TI  - [Effect of HCMV on p38MAPK, apoptosis and cell cycle of human glioma U251 cells].
AB  - OBJECTIVE: To study the changes of p38MAPK expressions, the frequency of
      apoptosis and the distribution of cell cycle of hunan Glioma U251 cells after
      HCMV infection. METHODS: The expression of total p38 (both phosphorylated and
      nonphosphorylated p38) and phosphorylated p38 in U251 cells were detected by
      Western blotting at 15 min, 30 min, 1 h, 6 h, 10 h, 16 h, 24 h, 36 h and 48 h
      after HCMV infection. The apoptosis percentage and the cell cycle distribution of
      U251 cells at 2 d, 5 d and 7 d after HCMV infection were detected by flow
      cytometry (FCM). RESULTS: The results of Western blotting demonstrated that a
      strong increase in phosphorylated p38 was detected from 6 h to 10 h after HCMV
      infection, with mean gray scales 186.33 +/- 7.51 (t = 5.37, P < 0.01) and 188.00
      +/- 7.02 (t = 5.26, P < 0.01 for all) at 6 h and 10 h, respectively, and p38
      phosphorylation decreased to the basic level at 16 h after HCMV infection. But
      the overall levels of p38 protein were not significantly altered during the
      course of infection. FCM analysis showed that HCMV could significantly increase
      the apoptotic rates of U251 cells compared with controls (t = 10.84, P < 0.01),
      and the apoptotic percentages of the cells reached to peak [(10.18 +/- 1.24)%] at
      5 d after HCMV infection. The data of FCM showed that HCMV could decrease the
      number of U251 cells in G1 phase and arrest the cells in S and G2 phase. The
      numbers of G1 phase U251 cells were significantly lowered to (56.50 +/- 2.57)% (t
      = 26.45, P < 0.01), (62.33 +/- 2.64)% (t = 21.20, P < 0.01) and (67.45 +/- 4.44)%
      (t = 10.61, P < 0.01), respectively at 2 d, 5 d and 7 d after infection.
      CONCLUSION: HCMV could activate p38MAPK pathway and trigger apoptosis and
      interfere cell cycle in U251 cells.

PMID- 17229386
TI  - [Mechanisms of arsenic trioxide induced tumor cell apoptosis in myelodysplastic
      syndrome mice model in vivo].
AB  - OBJECTIVE: To explore the possible mechanisms of cell apoptosis induced by
      arsenic trioxide (ATO) alone or in combination with thalidomide (THAL) on SCID
      mice model transplanted with human myelodysplastic syndrome (MDS) cell line MUTZ
      1 in vivo. METHODS: In a previous study by the authors, a Hum-MDS mice model was
      successfully established and the results showed that ATO alone or in combination
      with THAL had markedly inhibitory effect on the tumors growth in the MDS mice
      model of the treated groups with higher-rates of cell apoptosis and longer
      survival periods than control groups (P < 0.01). In the present study, 48 Hum-MDS
      mice were randomly grouped and ATO groups had 32 mice which were treated with ATO
      [5.0 microg or 7.5 microg/(g.d), 5 d a week, intraperitoneal injection (i.p.) x 3
      weeks alone or in combination with THAL 8 microg/(g.d) x 3 weeks] and the control
      groups had 16 mice [treated with 0.9% NaCl 10 microl/(g.d) (i.p) or untreated].
      The expressions of the proteins and the genes related to apoptosis were detected
      by using immunohistochemical (IHC) method, Western blot, reverse transcription
      polymerase chain reaction (RT-PCR), electrophoretic mobility shift assay (EMSA)
      with [gamma-32P] ATP oligonucleotide probe end labeling. RESULTS: (1) By IHC,
      compared to controls, the expressions of the pro-apoptosis protein Bax (F =
      1080.150, P < 0.01) and the ratio of Bax/Bcl-2 were higher, but Bcl-2 (F =
      2777.978, P < 0.01) was lower in the treated groups. (2) Western-blot results
      showed that the pro-apoptosis protein expressions of mitochondrial Smac/DIABLO
      and cytochrome C (IHC) were strikingly up-regulated and pro-caspase 9, 7, 6, 3
      and full PARP were down-regulated and cleaved caspase-6, 7, 9 and PARP were
      clearly observed in the treated groups. The expressions of apoptosis protein
      inhibitors of cIAP1 and survivin mRNA (RT-PCR) were markedly down-regulated in
      the treated groups. But no evidences of cleavage of BID and caspase-8 had been
      observed in any group. (3) The expression of IkappaB-alpha protein [nuclear
      factor-kappa B (NF-kappaB) inhibitor] was up-regulated (Western-blot) and the
      activity of NF-kappaB were sharply down-regulated in ATO-treated groups by EMSA.
      CONCLUSIONS: These results suggest that mitochondria are the primary
      intracellular target of ATO. At least, two pathways, namely, mitochondrial
      mediated-caspase dependent cell apoptosis pathway and NF-kappaB signal conduct
      pathway were involved in the mechanisms of ATO inducing cell apoptosis on MDS
      mice model in vivo. The mechanisms seem to be a complicated network regulated by
      multi-signal pathways, multi-layers, and multi-factors instead of a single
      pathway.

PMID- 17229387
TI  - [Screening of differentially expressed genes in rats with cardiomyopathy after
      bone marrow mesenchymal stem cell transplantation].
AB  - OBJECTIVE: Earlier studies have confirmed that mesenchymal stem cells (MSCs) can
      transdifferentiate into myocytes and improve heart function in 2 weeks. But the
      mechanism is not clear. In this study, the mechanism of improvement of heart
      function after transplantation of MSCs was examined with suppression subtractive
      hybridization (SSH). METHODS: MSCs were isolated from thighone and tibia of
      Wistar rats, purified by adhesion-screening method, and expanded in vitro.
      Intraperitoneal injection of doxorubicin (at 2.5 mg/kg/time and total doses of 15
      mg/kg) established cardiomyopathy models. MSCs were transplanted into
      cardiomyocytes. The differential genes between tester (rats with cardiomyopathy
      that were injected with MSCs) and driver (rats with cardiomyopathy that were
      injected with equivalent volume of culture medium) were screened with suppression
      subtractive hybridization. RESULTS: After 4 weeks of intraperitoneal injection of
      doxorubicin, left ventricular ejection fraction (LVEF) and left ventricular
      fractional shortening (LVFS) decreased by 26.48% and 40.61%, respectively (P <
      0.01), as compared with those of normal group. Cardiomyopathy model was
      established successfully. And the heart function of the rats with cardiomyopathy
      was significantly improved after transplantation. Sixteen gene fragments were
      detected, and 12 of them were up-regulated in testers. They were rattus
      norvegicus mitochondrial BN/SsNHsdMCW, rattus norvegicus strain mitochondrial
      F344 X BN F1, rattus norvegicus mitochondrion H(+)-ATP synthase alphase subunit
      (Atp5al) mRNA, rattus norvegicus BHE/Cdb tRNA-Lys gene, rat mitochondrial H(+)
      ATP synthase alpha subunit mRNA, rattus norvegic (wild-caught animal) complete
      mitochondrial genome, rattus norvegic clone BB.1.4.1 unknown Glu-Pro dipeptide
      repeat protein mRNA, Arabidopsis thaliana transgenic line C DNA, rat
      mitochondrial ATP synthase beta subunit mRNA, rattus norvegic mitochondrial
      genome, rat cardiac troponin T mRNA and rat mRNA for beta-globin. Four gene
      fragments were down-regulated in testers. They were rat mRNA for sarcomeric
      mitochondrial creatine kinase, rat mRNA for ribosomal phosphoprotein P2, rat
      alpha-crystallin B chain mRNA and rattus norvegicus NADH-ubiquinone
      oxidoreductase Fe-S protein 7 mRNA. CONCLUSION: The expression of the genes
      relating to mitochondrial synthesizing and contracting proteins synthesizing
      increased after MSC transplantation. The genes might enhance energy synthesis and
      promote MSC transdifferentiate into myocytes, and then improve heart function of
      rats with cardiomyopathy.

PMID- 17229388
TI  - [One case about Langerhans cell histiocytosis involving the thyroid in children].

PMID- 17229389
TI  - [Expression of Nogo-A mRNA and Nogo-A protein in brain tissue of neonatal mice
      with ischemic-hypoxic brain damage].

PMID- 17229390
TI  - [Clinical significance of balance between type 1 and type 2 immune responses of
      lymphocyte subpopulations in peripheral blood of children with aplastic anaemia].

PMID- 17229391
TI  - [A pediatric case of Graves' disease with dilated cardiomyopathy].

PMID- 17229392
TI  - [Suppurative meningoencephalitis complicated with intrinsic endophthalmitis in a
      newborn infant].

PMID- 17229393
TI  - [Requirements for English abstract of pediatric original article (X)].

PMID- 17229395
TI  - Neurocognitive characteristics of DUI recidivists.
AB  - Individuals who drive under the influence (DUI) of alcohol may be at greater risk
      for neurocognitive impairment because of their exposure to multiple sources of
      neurological risk. This could contribute to the persistence of DUI behaviour and
      influence the effectiveness of remedial interventions. The objectives of this
      study were to clarify the neurocognitive characteristics of DUI recidivists and
      the nature of potential impairments, and to explore relationships between these
      characteristics and the frequency of past DUI convictions. One hundred male
      recidivists were evaluated for visuospatial constructional abilities and visual
      memory, verbal fluency, attention skills, cognitive flexibility, spatial
      planning, and verbal and movement inhibition. Results indicated that a majority
      of recidivists showed signs of neurocognitive impairment on several dimensions.
      Impairment was most marked on visuospatial constructional abilities and visual
      memory. In contrast to previous studies, no participants were found to have
      impulse control problems. Measures of memory and cognitive efficiency were
      significantly associated with the frequency of past convictions. Finally,
      exploratory analyses of two potential sources of impairment, alcohol exposure and
      head trauma, suggested the role of excessive alcohol use as the most obvious
      associated factor. Overall, the findings indicate that neurocognitive impairments
      are a common feature in recidivists and may contribute to DUI persistence.
      Development of a DUI-specific neurocognitive assessment and greater understanding
      of how neurocognitive status influences DUI risk could lead to remediation
      strategies better adapted to the individual characteristics of recidivists.

PMID- 17229397
TI  - Effective properties of suspensions/emulsions, porous and composite materials.
AB  - A new method (a version of a mean field method) is suggested to calculate
      effective properties of suspensions/emulsions, porous and dispersed materials.
      The aim is to demonstrate a wide range of applicability of the new method. To
      show the idea of the new method the dependence of the effective diffusion
      coefficient in the porous medium on the porosity is deduced. Based on the same
      method the following dependences are deduced: the effective viscosity of
      suspensions and emulsions as functions of volume fraction of suspended particles
      or droplets, elastic modules of rubber/polymer sheets with cracks and elastic
      modules of composite materials on the volume fraction of inclusions in the case
      of an arbitrary number of different types of inclusions. In all cases the
      calculated dependences are compared with available experimental data and
      published theoretical models.

PMID- 17229396
TI  - Perception, attitudes and beliefs, and openness to change: implications for older
      driver education.
AB  - With a rapidly aging population, strategies for improving driver safety are
      beginning to emerge that focus on changing driving behaviors and knowledge. We
      examined the perceptions of risk, beliefs and attitudes, and openness to change
      of 86 older participants voluntarily attending a driver education program. It
      appeared that most people attending these sessions were not necessarily concerned
      about their own driving, safety or abilities, but were interested in maintaining
      mobility. They were conservative and reasonably consistent in their attitudes
      toward traffic regulations and safe driving practices. Some gender differences
      emerged with more men than women being resistant to changing their driving
      habits, more men than women reporting that they drive after consuming alcohol and
      more women than men identifying a role for their families in decision-making
      regarding driving cessation. This suggests that educational material may need to
      be targeted differently for men and women. It is anticipated that psychosocial
      factors related to driving such as driver perception, beliefs and openness to
      change will be useful for maximizing the fit between education program content
      and outcomes.

PMID- 17229398
TI  - Microemulsions as carriers for drugs and nutraceuticals.
AB  - Microemulsions are potentially excellent carriers for bioactive molecules. They
      offer the advantage of spontaneous formation, ease of manufacture, thermodynamic
      stability, and improved solubilization of bioactive materials. This review
      explores some of the new trends in microemulsion research through analysis of
      some representative studies. The solubilization of different classic drugs,
      peptides, and nutraceuticals in various oral microemulsion compositions and
      microstructures was reviewed. It was found that even W/O microemulsions, which
      are expected to break upon dilution in the digestive tract, increase the
      permeability and bioavailability of drugs. Thus, it seems that component
      selection (the use of molecules that can act as permeability enhancers) is of
      great importance. Structures such as self-microemulsifying drug delivery systems
      (SMEDDS), W/O, bicontinuous, and O/W microemulsions, were closely examined, and
      their potential to serve as drug carriers was evaluated. It seems that for
      microemulsion systems to be used as vehicles for bioactive materials, the
      formulations should be based on SMEEDS, which form O/W upon dilution to a
      specific water content. U-type microemulsions are actually an improved SMEDDS
      formulation, capable of being diluted with any given water concentration. Much
      research is being conducted on microemulsion microstructure since there is an
      obvious direct connection between the microstructure, solubilization capacity,
      and bioavailability of the active molecules.

PMID- 17229399
TI  - Loss of control over eating reflects eating disturbances and general
      psychopathology.
AB  - This study examined the clinical significance of the loss of control over eating
      as a key component of eating disorders. It investigated the association of eating
      related psychopathology and general psychopathology with objective bulimic
      episodes (OBEs; experiencing a loss of control while consuming large amounts of
      food) and subjective bulimic episodes (SBEs; experiencing a loss of control while
      consuming small/moderate amounts). A community sample of 81 women with a range of
      disordered eating was recruited: binge-eating disorder, bulimia nervosa,
      subclinical eating disturbances, or no eating disorders. They were interviewed
      using the Eating Disorder Examination and completed measures of eating-related
      and general psychopathology. Both OBE and SBE frequencies correlated
      significantly with measures of eating-related and general psychopathology, and no
      significant differences were found between the magnitudes of the correlations
      with either binge episode type. SBE frequency significantly and independently
      predicted global eating disorder psychopathology. The loss of control over
      eating, without consuming large amounts of food, was as closely associated with
      specific eating disorder psychopathology and general mental health as were
      traditionally defined OBEs. SBEs may be an important target of treatment and
      should be considered for future diagnostic classifications of eating disorders.

PMID- 17229400
TI  - The relationship between bullying, psychotic-like experiences and appraisals in
      14-16-year olds.
AB  - The psychological consequences of bullying have been the focus of much research
      over the last 25 years. However, the relationship between bullying and psychotic
      experiences has been relatively ignored despite the weight of evidence which
      suggests that traumatic events in childhood are significantly related to
      psychotic disorders. 373 pupils aged between 14 and 16 years took part in the
      study. They were asked to complete a number of self-report measures which
      examined their experience of bullying, predisposition to auditory hallucinations,
      paranoia and dissociation, and beliefs about both the self and the world and
      about paranoia. It was found that bullying was significantly associated with
      predisposition to psychotic experiences. Negative post-trauma cognitions were
      also associated with predisposition to psychotic phenomena as were positive
      beliefs about paranoia. Being bullied at school and beliefs about trauma and
      psychotic symptoms may contribute to the development of psychosis. However, it is
      also possible that these results indicate that experiencing psychotic-like
      phenomena increases the likelihood that a pupil's interpersonal context is
      characterised by peer hostility and rejection. The implications of these results
      are discussed.

PMID- 17229401
TI  - Rosmarinic acid inhibits indoleamine 2,3-dioxygenase expression in murine
      dendritic cells.
AB  - Indoleamine 2,3-dioxygenase (IDO), a key enzyme that catalyses the initial and
      rate-limiting step in the degradation of the tryptophan, is simultaneously
      expressed in murine dendritic cells and macrophages stimulated with interferon
      gamma (IFN-gamma). In the present study, we investigated whether rosmarinic acid
      (RA), which is suggested to exhibit anti-oxidant and anti-cyclooxygenase
      properties, could suppress the functional expression of IDO in murine bone marrow
      derived dendritic cells (BMDCs) stimulated with IFN-gamma. Treatment with RA
      reduced intracellular expression of IDO both in IFN-gamma-activated BMDCs in
      vitro and in CD11c(+)CD8alpha(+) DCs in vivo tumor-bearing mice model.
      Consequently, we obtained evidence that RA suppresses the functional activity of
      IDO and blocks the IDO-dependent T cell suppression. In IFN-gamma-mediated
      induction of IDO transcription, activation of the signal transducer and activator
      of transcription 1 (STAT1) is important to be express IDO in IFN-gamma-stimulated
      BMDCs. In this study, we demonstrated that the RA could also suppress IFN-gamma
      induced STAT1 activation. These novel findings provide a new insight into that RA
      as a pharmacological and transcriptional inhibitor of IDO is worthy of clinical
      application as well as further investigation for IDO regulation.

PMID- 17229403
TI  - Event-related beta EEG-changes during passive and attempted foot movements in
      paraplegic patients.
AB  - A number of electroencephalographic (EEG) studies report on motor event-related
      desynchronization and synchronization (ERD/ERS) in the beta band, i.e. a decrease
      and increase of spectral amplitudes of central beta rhythms in the range from 13
      to 35 Hz. Following an ERD that occurs shortly before and during the movement,
      bursts of beta oscillations (beta ERS) appear within a 1-s interval after
      movement offset. Such a post-movement beta ERS has been reported after voluntary
      hand movements, passive movements, movement imagination, and also after movements
      induced by functional electrical stimulation. The present study compares ERD/ERS
      patterns in paraplegic patients (suffering from a complete spinal cord injury)
      and healthy subjects during attempted (active) and passive foot movements. The
      aim of this work is to address the question, whether patients do have the same
      focal beta ERD/ERS pattern during attempted foot movement as healthy subjects do.
      The results showed midcentral-focused beta ERD/ERS patterns during passive,
      active, and imagined foot movements in healthy subjects. This is in contrast to a
      diffuse and broad distributed ERD/ERS pattern during attempted foot movements in
      patients. Only one patient showed a similar ERD/ERS pattern. Furthermore, no
      significant ERD/ERS patterns during passive foot movement in the group of the
      paraplegics could be found.

PMID- 17229404
TI  - Effects of syntactic complexity in L1 and L2; an fMRI study of Korean-English
      bilinguals.
AB  - The neural mechanisms underlying the syntactic processing of sentence
      comprehension in Korean (L1) and English (L2) by late bilinguals were
      investigated using functional MRI. The Korean native speakers were asked to read
      sentences with different levels of syntactic complexity in L1 and L2 and respond
      to comprehension questions concerning the sentences. The syntactic complexity was
      varied using a center-embedded sentence "The director that the maid introduced
      ignored the farmer" or a conjoined sentence "The maid introduced the director and
      ignored the farmer". It was found that the major areas involved in sentence
      processing such as the left inferior frontal gyrus (IFG), bilateral inferior
      parietal gyrus, and occipital lobe including cuneus, and lingual gyrus were
      commonly activated during the processing of both L1 and L2. However, the pattern
      of activation was different for L1 and L2 in the left IFG. The amount of
      activation was greater for embedded sentences than for conjoined sentences in L1
      while no difference was found in L2. These results suggest that the cortical
      areas involved with syntactic processing in L1 and L2 are shared, but that the
      underlying neural mechanisms are different. The findings of the present study are
      discussed in comparison with Hasegawa et al.'s (Hasegawa, M., Carpenter, P.A.,
      Just, M.A., 2002. An fMRI study of bilingual sentence comprehension and workload.
      NeuroImage 15, 647-660.) and Yokoyama et al.'s (Yokoyama, S., Okamoto, H.,
      Miyamoto, T., Yoshimoto, K., Kim, J., Iwata, K., Jeong, H., Uchida, S., Ikuta,
      N., Sassa, Y., Nakamura, W., Horie, K., Sato, S., Kawashima, R., 2006. Cortical
      activation in the processing of passive sentences in L1 and L2: An fMRI study.
      NeuroImage 30, 570-579.) studies which also found common areas of activation but
      different patterns of activation during the processing of L1 and L2.

PMID- 17229402
TI  - Regulation of alpha2AR trafficking and signaling by interacting proteins.
AB  - The continuing discovery of new G protein-coupled receptor (GPCR) interacting
      proteins and clarification of the functional consequences of these interactions
      has revealed multiple roles for these events. Some of these interactions serve to
      scaffold GPCRs to particular cellular micro-compartments or to tether them to
      defined signaling molecules, while other GPCR-protein interactions control GPCR
      trafficking and the kinetics of GPCR-mediated signaling transduction. This review
      provides a general overview of the variety of GPCR-protein interactions reported
      to date, and then focuses on one prototypical GPCR, the alpha(2)AR, and the in
      vitro and in vivo significance of its reciprocal interactions with arrestin and
      spinophilin. It seems appropriate to recognize the life and career of Arthur
      Hancock with a summary of studies that both affirm and surprise our preconceived
      notions of how nature is designed, as his career-long efforts similarly affirmed
      the complexity of human biology and attempted to surprise pathological changes in
      that biology with novel, discovery-based therapeutic interventions. Dr. Hancock's
      love of life, of family, and of commitment to making the world a better place are
      a model of the life well lived, and truly missed by those who were privileged to
      know, and thus love, him.

PMID- 17229405
TI  - GABA-mediated oxytocinergic inhibition in dorsal horn neurons by hypothalamic
      paraventricular nucleus stimulation.
AB  - In anaesthetized rats, we tested whether the unit activity of dorsal horn neurons
      that receive nociceptive input is modulated by electrical stimulation of the
      hypothalamic paraventricular nucleus (PVN). An electrophysiological mapping of
      dorsal horn neurons at L3-L4 let us choose cells responding to a receptive field
      located in the toes region of the left hindpaw. Dorsal horn neurons were
      classified according to their response properties to peripheral stimulation. Wide
      Dynamic Range (WDR) cells responding to electrical stimulation of the peripheral
      receptive field and presenting synaptic input of Adelta, Abeta, and C-fibers were
      studied. Suspected interneurons that are typically silent and lack peripheral
      receptive field responses were also analyzed. PVN electrical stimulation inhibits
      Adelta (-55.0+/-10.2%), C-fiber (-73.1+/-6.7%), and post-discharge (-75.0+/-8.9%)
      peripheral activation in WDR cells, and silent interneurons were activated. So,
      this last type of interneuron was called a PVN-ON cell. In WDR cells, the
      inhibition of peripheral responses caused by PVN stimulation was blocked by
      intrathecal administration of a specific oxytocin antagonist or bicuculline.
      However, PVN-ON cell activation was blocked by the same specific oxytocin
      antagonist, but not by bicuculline. Our results suggest that PVN stimulation
      inhibits nociceptive peripheral-evoked responses in WDR neurons by a descending
      oxytocinergic pathway mediated by GABAergic PVN-ON cells. We discuss our
      observation that the PVN electrical stimulation selectively inhibits Adelta and C
      fiber activity without affecting Abeta fibers. We conclude that Adelta and C
      fibers receive a presynaptic inhibition mediated by GABA.

PMID- 17229406
TI  - The influence of rTMS over the right dorsolateral prefrontal cortex on top-down
      attentional processes.
AB  - Repetitive Transcranial Magnetic Stimulation (rTMS) provides a unique opportunity
      to study causal relationships between activity in the dorsolateral prefrontal
      cortex (DLPFC) and executive functioning, by modulating brain activity in SHAM
      controlled designs. We devised a new Stroop task paradigm in which subjects must
      engage in both strategic and automatic attentional processes. In the current
      experiment, we manipulated subjects' expectancies for incongruent stimuli.
      Previous research demonstrated that when subjects have a high level of expectancy
      that a stimulus will be incongruent, they are able to strategically adjust the
      relative influence of word reading on color naming. The effect of high frequency
      (HF) rTMS on Stroop performance of 20 right-handed healthy female volunteers was
      tested using a double blind within subjects design by counterbalanced crossover
      sham (placebo) and active rTMS over the right DLPFC. Since mood remained
      unchanged after rTMS, the Stroop data could be evaluated independent of mood
      changes. Only in the high expectancy condition, we found a decreased response
      time to both congruent and incongruent trials on the Stroop task performance
      after HF rTMS. The SHAM placebo condition yielded no effects. We conclude that
      high frequency stimulation over the right DLPFC has an effect on top-down
      attentional processes by modulating the attentional set.

PMID- 17229407
TI  - Differential RIP antigen (CNPase) expression in peripheral ensheathing glia.
AB  - The RIP monoclonal antibody is commonly used to identify oligodendrocytes.
      Recently, the RIP antigen was identified as 2',3'-cyclic nucleotide 3'
      phosphodiesterase (CNPase), a known non-compact myelin protein [Watanabe, M.,
      Sakurai, Y., Ichinose, T., Aikawa, Y., Kotani, M., Itoh, K., 2006. Monoclonal
      antibody Rip specifically recognizes 2',3'-cyclic nucleotide 3'-phosphodiesterase
      in oligodendrocytes. J. Neurosci. Res. 84, 525-533]. In the present study we
      characterize normal and axotomy-induced changes in RIP immunoreactivity in
      peripheral glia. In myelinating Schwann cells, RIP demarcated paranodal regions
      of myelinated axons and clearly defined Schmidt-Lantermann incisures.
      Surprisingly, RIP immunoreactivity was not confined to myelinating glia. Robust
      RIP immunoreactivity was present in Remak bundles in mixed nerves and in
      sympathetic ganglia and grey rami. Following peripheral nerve injury, RIP
      immunoreactivity was redistributed diffusely throughout de-differentiating
      Schwann cell cytoplasm. In uninjured rats, low levels of RIP immunoreactivity
      were detectable in satellite cells surrounding dorsal root ganglion (DRG) neurons
      and in terminal Schwann cells at neuromuscular junctions. This pattern suggested
      a correlation between RIP immunoreactivity and the amount of axon-glial contact.
      We therefore injured the L5 spinal nerve to induce sympathetic sprouting and
      pericellular basket formation in the DRG, and asked whether relatively RIP
      negative satellite glia, which normally contact only neuronal somata, would
      upregulate the RIP antigen upon contact with sprouting sympathetic axons. All
      perineuronal sympathetic sprouts infiltrated heavily RIP-immunoreactive satellite
      cell sheaths. RIP immunoreactivity was absent from placode-derived olfactory
      ensheathing glia, indicating that the relationship between axon-glial contact and
      RIP-immunoreactivity is restricted to peripheral ensheathing glia of the neural
      crest-derived Schwann cell lineage.

PMID- 17229408
TI  - Transient suppression of the vesicular acetylcholine transporter in urinary
      bladder pathways following spinal cord injury.
AB  - The aim of this study was to examine the expression profile of the vesicular
      acetylcholine transporter (VAChT), which is a cholinergic pre-synaptic marker, in
      the lower neural tract following spinal cord injury (SCI) and its effect on
      coordination of micturition. In adult female Sprague-Dawley rats, SCI was induced
      by complete transection of the spinal cord at T9. At various time points, 3, 7,
      14 and 28 days, after SCI, cystometry was performed on conscious rats. Bladder
      areflexia was observed during the first week. Twenty-eight days after SCI the
      rats showed reflex contractions and voiding. The expression of VAChT was examined
      with immunohistochemistry. The number of VAChT-positive nerve terminals, which
      were surrounding neuronal soma, was transiently decreased in pelvic ganglion and
      spinal cord (L1, L2, L6 and S1). In particular VAChT terminals surrounding motor
      neurons in the ventral horn and autonomic pre-ganglion cells were dramatically
      decreased from 3 to 14 days after SCI. Similarly, and the number of VAChT
      positive fibers in the bladder wall was also decreased. The intensity of VAChT
      terminals recovered in all above regions in conjunction with recovery of bladder
      function. These observations indicate that the transient decrease of the VAChT
      positive nerve might cause a failure of cholinergic neuronal transmission along
      the urinary bladder tract after SCI. As the cholinergic system was recovered at
      least in rat, the functional recovery of neurogenic bladder syndrome in SCI
      patients may become possible by further understanding the mechanism underlying
      the recovery of cholinergic system in rat.

PMID- 17229409
TI  - The striatum and probabilistic implicit sequence learning.
AB  - The distinction between implicit (unconscious) and explicit (conscious) learning
      is controversial. Some argue that explicit learning is dependent on the medial
      temporal lobes, whereas implicit learning is mediated by the basal ganglia and
      others propose that all learning is explicit. The purpose of the present study
      was to investigate the involvement of the basal ganglia in implicit learning by
      examining learning of a probabilistic sequence of targets, in patients with
      Parkinson's disease (PD) and controls. Following learning, we assessed
      participants' awareness of the sequence structure by asking them to generate or
      withhold sequence consistent responses (process dissociation procedure) and to
      perform a recognition test in which measures of priming and recognition were
      obtained concurrently. Although the PD group demonstrated evidence of
      probabilistic sequence learning in this study, learning was significantly
      attenuated compared to controls. Residual learning in the PD group was genuinely
      implicit in nature because (a) PD patients were not able to control the
      expression of their acquired knowledge, and (b) their knowledge supported
      subsequent priming of sequence-consistent responses but recognition ratings were
      at chance. In contrast, following learning controls were capable of above chance
      recognition indicating that their sequential knowledge was acquired in a more
      explicit way. The results support the view that (i) the basal ganglia contribute
      to probabilistic implicit sequence learning (ii) that such learning can occur
      implicitly without explicit knowledge in PD patients.

PMID- 17229410
TI  - Arthritis-induced increase in cholecystokinin release in the rat anterior
      cingulate cortex is reversed by diclofenac.
AB  - Given a hypothesised role for CCK in the anterior cingulate cortex (ACC) for the
      sensation of pain, the aim of the present study was to investigate whether the
      increased CCK release could be affected by two different analgesic drugs,
      morphine and the non-selective cyclooxygenase inhibitor diclofenac. Since opioids
      stimulate CCK release in other CNS regions we have also studied the effect of
      morphine by itself on the CCK-LI release in the ACC of non-arthritic rats. Three
      to seven hours after intraarticular carrageenan injection, at the time when the
      animals are known to show pain-related behaviour, in vivo microdialysis in awake
      rats revealed increased CCK-LI release in the ACC. The CCK-LI release was
      significantly attenuated by diclofenac (25 mg/kg i.m.), but not by morphine (10
      mg/kg s.c.). Neither diclofenac (25 mg/kg i.m.) nor morphine (5 or 10 mg/kg s.c.)
      affected the CCK-LI release in the ACC in non-arthritic rats. The results
      obtained with diclofenac indicate that prostaglandins contribute to the increased
      CCK-LI release in the ACC during monoarthritis. However, the lack of effect of
      morphine suggests that the CCK release in the ACC is not directly related to the
      sensation of pain. Further on, the failure of morphine to affect the
      extracellular level of CCK-LI in the ACC in control animals as well as in animals
      with carrageenan-induced monoarthritis is in contrast to previous studies on the
      frontal cortex or the dorsal horn of the spinal cord, in which similar doses of
      morphine stimulate CCK release. Thus, compared to these regions, CCK release may
      be differently regulated in the ACC.

PMID- 17229411
TI  - The Hofer-Moest decarboxylation of D-glucuronic acid and D-glucuronosides.
AB  - Research was undertaken to effect the oxidative decarboxylation of
      glycuronosides. Experiments with free D-glucuronic acid and aldonic acids were
      also executed. Both anodic decarboxylation and variants of the Ruff degradation
      reaction were investigated. Anodic decarboxylation was found to be the only
      successful method for the decarboxylation of glucuronosides. It was, therefore,
      proposed that glycuronosides can only undergo a one-electron oxidation to form an
      acyloxy radical, which decomposes to form carbon dioxide and a C-5 radical, that
      is, a Hofer-Moest decarboxylation. The radical is subsequently oxidized to a
      cation by means of a second one-electron oxidation. The cation undergoes
      nucleophilic attack from the solvent (water), whose product (a hemiacetal)
      undergoes a spontaneous hydrolysis to yield a dialdose (xylo-pentodialdose from D
      glucuronosides).

PMID- 17229412
TI  - Structural view of glycosaminoglycan-protein interactions.
AB  - The essential role of protein-glycosaminoglycan interactions in the regulation of
      various physiological processes has been recognized for several decades but it is
      only recently that the molecular basis underlying such interactions has emerged.
      The different methodologies to elucidate the three-dimensional features of
      glycosaminoglycans along with the interactions with proteins cover high
      resolution NMR spectroscopy, X-ray crystallography, molecular modeling, and
      hydrodynamic measurements. The structural results that have accumulated have been
      organized in databases that allow rapid searching with entries related either to
      the type of glycosaminoglycan or the type of protein. Finally, three selected
      examples enlightening the complexity of the nature of the interactions occurring
      between proteins and glycosaminoglycans are given. The example of interactions
      between heparin and antithrombin III illustrates how such a complex mechanism as
      the regulation of blood coagulation by a specific pentasaccharide can be
      dissected through the combined use of dedicated carbohydrate chemistry and
      structural glycobiology. The second example deals with the study of complexes
      between chemokines and heparin, and shows how multimolecular complexes of
      proteins can be organized in space throughout the action of glycosaminoglycans.
      Again, the synthesis of chemical mimetics offers an unexpected route to the
      development of novel glycotherapeutics. Finally, the area of
      enzymes/glycosaminoglycans complexes is briefly covered to realize the limited
      knowledge that we have for such an important class of biomacromolecular
      complexes.

PMID- 17229413
TI  - A follow-up study of women in the synthetic rubber industry: study methods.
AB  - BACKGROUND: Concerns about the possible toxic effects of workplace exposures in
      the synthetic rubber industry have centered on 1,3-butadiene (BD), styrene and
      dimethyldithiocarbamate (DMDTC). Our previous mortality studies of over 17,000
      male synthetic rubber workers found an excess of leukemia that may be due to BD
      or BD plus other chemicals. Experimental studies have shown that BD produces
      mammary tumors in female mice and rats and ovarian tumors in female mice. AIM:
      This paper presents the methods of a follow-up study that evaluates the mortality
      experience of women employed in the North American synthetic rubber industry.
      METHODS: Women employed for at least 1 day at any of eight North American styrene
      butadiene rubber plants were followed up from 1943 to 2002. Identifying and work
      history information were obtained from personnel records. Estimated quantitative
      exposure to BD, styrene and DMDTC, developed for our previous study of men, were
      used in this study. External analyses use the standardized mortality ratios
      (SMRs) to compare the cohort's cause-specific mortality rates to the rates of the
      female general population of the states or the province where the plants are
      located. Internal analyses use the Poisson regression and Cox proportional
      hazards models to examine specific cancer mortality rates in relation to BD,
      styrene and DMDTC exposure, by comparing an exposed cohort subgroup with the rate
      of unexposed cohort members.

PMID- 17229414
TI  - Structure-activity relationships for halobenzene induced cytotoxicity in rat and
      human hepatocytes.
AB  - Halobenzenes are ubiquitous environmental contaminants, which are hepatotoxic in
      both rodents and humans. The molecular mechanism of halobenzene hepatotoxicity
      was investigated using Quantitative structure-activity relationships (QSAR) and
      accelerated cytotoxicity mechanism screening (ACMS) techniques in rat and human
      hepatocytes. The usefulness of isolated hepatocytes for prediciting in vivo
      xenobiotic toxicity was reassessed by correlating the LC(50) of 12 halobenzene
      congeners in phenobarbital (PB) induced rat hepatocytes in vitro determined by
      ACMS to the hepatotoxicities reported in vivo in PB-induced male Sprague-Dawely
      (SD) rats. A high correlation (r(2)=0.90) confirmed the application of
      hepatocytes as a "gold standard" for toxicity testing in vitro. QSARs were
      derived to determine the physico-chemcial variables that govern halobenzene
      toxicity in PB-induced rat, normal rat and human hepatocytes. We found that
      toxicity in normal rat and normal human hepatocytes both strongly correlate with
      hydrophobicity (logP), ease of oxidation (E(HOMO), energy of the highest
      molecular orbital) and on the asymmetric charge distribution according to
      arrangement of halogen substituents (dipole moment, mu). This suggests that
      halobenzene interaction with cytochrome P450 for oxidation is the metabolic
      activating path for toxicity and is similar in both species. In PB-induced rat
      hepatocytes the QSAR derivation is changed, where halobenzene toxicity strongly
      correlates to logP and dipole moment, but not E(HOMO). The changed QSAR suggests
      that oxidation is no longer the rate-limiting step in the cytotoxic mechanism
      when CYP2B/3A levels are increased, confirming CYP450 oxidation as the metabolic
      activating step under normal conditions.

PMID- 17229416
TI  - DRAQ5: improved flow cytometric DNA content analysis and minimal residual disease
      detection in childhood malignancies.
AB  - BACKGROUND: The majority of flow cytometric DNA content analyses are performed on
      whole peripheral blood, bone marrow or tumor samples containing significant
      numbers of non-malignant cells which hamper specific DNA content analysis.
      Simultaneous analysis of DNA content and immunophenotype greatly improves the
      specificity of DNA-ploidy measurements. Therefore, a three-color flow cytometric
      assay using DRAQ5 was developed and validated. METHODS: The results of DNA
      content analysis using DRAQ5 and propidium iodide were compared using peripheral
      blood samples of 15 healthy volunteers. The reproducibility of the multiparameter
      DRAQ5 assay was assayed in 10 analytical runs and the sensitivity was evaluated
      with addition experiments. RESULT: Using DRAQ5, slightly wider CVs of the G0/G1
      peak were obtained (average CV=3.29%). When DRAQ5 staining and immunophenotyping
      were combined, the within- and between-run imprecision was 1.98% and 1.67%,
      respectively and the DNA content of 25 DNA-hyperdiploid tumor cells (DNA
      index=1.16) per 4.10(4) mononuclear cells (0.06%) could be determined.
      CONCLUSIONS: The multiparameter DRAQ5 assay has a superior sensitivity and
      specificity compared to the propidium iodide based method. Since at least 25 DNA
      hyperdiploid cells per 10(4) DNA-diploid mononuclear cells could be detected,
      multiparameter DRAQ5 DNA content analysis could be used to study minimal residual
      disease.

PMID- 17229417
TI  - Switchover mechanism for very-low-density lipoprotein modulation of triglyceride
      handling.

PMID- 17229415
TI  - Computer-aided drug discovery and development (CADDD): in silico-chemico
      biological approach.
AB  - It is generally recognized that drug discovery and development are very time and
      resources consuming processes. There is an ever growing effort to apply
      computational power to the combined chemical and biological space in order to
      streamline drug discovery, design, development and optimization. In biomedical
      arena, computer-aided or in silico design is being utilized to expedite and
      facilitate hit identification, hit-to-lead selection, optimize the absorption,
      distribution, metabolism, excretion and toxicity profile and avoid safety issues.
      Commonly used computational approaches include ligand-based drug design
      (pharmacophore, a 3D spatial arrangement of chemical features essential for
      biological activity), structure-based drug design (drug-target docking), and
      quantitative structure-activity and quantitative structure-property
      relationships. Regulatory agencies as well as pharmaceutical industry are
      actively involved in development of computational tools that will improve
      effectiveness and efficiency of drug discovery and development process, decrease
      use of animals, and increase predictability. It is expected that the power of
      CADDD will grow as the technology continues to evolve.

PMID- 17229418
TI  - Predicted effects of hemoglobin A1c assay precision on a patient population
      distribution of serial hemoglobin A1c difference values.
AB  - BACKGROUND: Interpretation of serial measurements of % hemoglobin A1c includes an
      assessment of differences from preceding values (DHbA1c). We examined predicted
      effects of different assay precisions on an observed population distribution for
      DHbA1c. METHODS: Primary data were 5260 DHbA1c values from sequential HbA1c
      measurement pairs obtained within 1 calendar year. Each DHbA1c was replaced by a
      distribution obtained from sampling each component HbA1c value according to a
      normal distribution characterized by a fixed coefficient of variation (CV) of
      either 1%, 3% or 5% (forming data sets A, B and C, respectively). Data sets B and
      C, with inferior precision, were compared with the reference data set A (highest
      precision). RESULTS: Using DHbA1c bin widths of 0.5% HbA1c, differences in assay
      precision caused significant redistribution of numbers within bins. For instance,
      for CV=5%, there was a 7.2% decrease in the number of results within the DHbA1c
      bin=(-0.5 to<or=0.0)% compared with the number for CV=1%, and a 6.4% increase in
      numbers of results for DHbA1c>0.5. CONCLUSION: Different HbA1c assay CVs can
      significantly affect the fraction of patients within different clinical
      categorizations for DHbA1c and consequently may differently influence patient
      care recommendations.

PMID- 17229419
TI  - Time-course of quantitative urinary leukocytes and bacteria counts during
      antibiotic therapy in women with symptoms of urinary tract infection.
AB  - BACKGROUND: Urinary tract infections are generally diagnosed by test strips and
      microscopic semi-quantitative sediment analyses. However, results are uncertain
      because of lacking standardisation and limited sensitivity in low-count
      bacteriuria. Flow cytometry UF-100 was used to analyse particles quantitatively
      in urine in women with urinary tract infections during the period of antibiotic
      therapy. The aim was to follow the courses of leukocytes and bacteria during
      infections and to gain information about the reasons for successful or
      unsuccessful outcomes. METHOD: Quantitative leukocytes and bacterial counts in
      urine of 16 symptomatic women were performed at presentation and each day during
      the antibiotic treatment by flow cytometry UF-100. RESULTS: Leukocytes in urine
      were between 30 and 15,000 (x10(6)/L) at presentation (cut-off 20x10(6)/L).
      Bacteria counts from flow cytometry were mainly 5x10(9)/L-100x10(9)/L (cut-off of
      3x10(9)/L). The deepest decreases in cell counts were noted during the first 24 h
      after initiation of therapy and gained normal values at the end of treatment in
      successful outcomes. A slower or no decrease was noted in unsuccessful
      treatments. CONCLUSION: The precise leukocyte and bacteria counting by flow
      cytometry and their follow-up during urinary tract infections gave early
      information about outcomes of therapy.

PMID- 17229420
TI  - 3D heart model for computer simulations in cardiac surgery.
AB  - For a satisfactory computer simulation, a model, which imitates a natural
      situation, is needed. The Human heart is an irregular 3D object and thus
      difficult to reproduce. Basic data was taken from Visible Human Dataset (VHD),
      National Library of Medicine. The heart area was cut out of the original cross
      sections and different tissues segmented. All the slices also had to be aligned
      to assure precise overlapping of the structures. A 3D computer heart model with
      the resolution of 1mm was designed. The heart model was dedicated to simulations
      of heat transfer during heart surgery however, it is applicable also to other
      medical simulations.

PMID- 17229421
TI  - Free and chromatin-associated mono-, di-, and trimethylation of histone H4-lysine
      20 during development and cell cycle progression.
AB  - Methylation of specific amino acids in histone tails is responsible for packaging
      DNA into condensed, repressed chromatin, and into open chromatin that is
      accessible to the transcription machinery. Monomethylation and trimethylation of
      histone H4-lysine 20 (H4-K20) control the formation of repressed chromatin. Using
      antibodies that specifically recognize the three methyl marks of histone H4-K20,
      we characterized their regulation during the cell cycle and throughout
      development. We find free mono- and trimethylated histone H4-K20 in unfertilized
      Drosophila eggs and in S2 tissue culture cells. Soluble mono-. di-, and
      trimethylated H4-K20 are also found in HeLa cells. These soluble modified
      histones may represent a pool of free histones that can rapidly be incorporated
      into chromatin. The three methyl marks are each regulated differentially during
      development and their detection on western blots does not overlap with their
      detection on chromosomes. Monomethylated H4-K20 is detected on condensed
      chromosomes throughout development, while di- and trimethylated H4-K20 are
      detected on metaphase chromosomes at specific stages. Our results suggest that
      the detection of methylated H4-K20 on chromosomes may reveal chromatin packaging
      rather than the distribution of the methyl marks.

PMID- 17229422
TI  - Cordycepin (3'-deoxyadenosine) inhibits human platelet aggregation in a cyclic
      AMP- and cyclic GMP-dependent manner.
AB  - Cordycepin (3'-deoxyadenosine) is isolated from Cordyceps militaris, a species of
      the fungal genus Cordyceps. Cordycepin is an ingredient used in traditional
      Chinese medicine and is prescribed for various diseases, such as cancer and
      chronic inflammation. In this study, we investigated the novel effect of
      cordycepin (3'-deoxyadenosine) on collagen-induced human platelet aggregation.
      Cordycepin inhibited dose-dependently collagen-induced platelet aggregation in
      the presence of various concentrations of exogenous CaCl(2). Of two aggregation
      inducing molecules, cytosolic free Ca(2+) ([Ca(2+)](i)) and thromboxane A(2)
      (TXA(2)), cordycepin (500 microM) blocked the up-regulation of [Ca(2+)](i), by up
      to 74%, but suppressed TXA(2) production by 46%. Subsequently, Ca(2+)-dependent
      phosphorylation of both 47-kDa and 20-kDa proteins in collagen-treated platelets
      was potently diminished by cordycepin. However, upstream pathways for producing
      these two inducers, such as the activation of phospholipase C-gamma2 (PLC-gamma2)
      (assessed by the phosphotyrosine level) and the formation of inositol 1,4,5
      trisphosphate (IP(3)), were not altered by cordycepin. Cordycepin increased the
      level of second messengers adenosine 3',5'-cyclic monophosphate (cAMP) and
      guanosine 3',5'-cyclic monophosphate (cGMP) in collagen-stimulated platelets.
      Whereas the NO-sensitive guanylyl cyclase inhibitor ODQ did not alter the
      cordycepin-induced up-regulation of cGMP, the adenylyl cyclase inhibitor SQ22536
      completely blocked the cAMP enhancement mediated by cordycepin, indicating that
      cordycepin had different modes of action. Therefore, our data suggest that the
      inhibitory effect of cordycepin on platelet aggregation might be associated with
      the down-regulation of [Ca(2+)](i) and the elevation of cAMP/cGMP production.

PMID- 17229423
TI  - Effects of local anaesthesia on subdermal needle insertion pain and subsequent
      tests of microvascular function in human.
AB  - Post-occlusive and local thermal hyperemia are currently used as integrated tests
      to study microvascular function in microvascular diseases. However, further
      pathophysiological insight would require its association with microdialysis. The
      major limitation remains the microinvasive approach as local anaesthesia prior to
      fiber insertion could lead to confounding effects. The objective of our study was
      to determine whether EMLA cream treatment, applied for 20 min, 40 or 60 min,
      significantly decreases the pain related to intradermal needle insertions, while
      not decreasing the microvascular response to post-occlusive and thermal hyperemia
      2 h after cream removal. EMLA cream, when applied during 40 min, induces a
      significant 75% decrease in the pain following intradermal needle insertion,
      while not modifying skin post-occlusive and thermal hyperemia 2 h after cream
      removal. Therefore, we recommend its use in such conditions before performing
      microdialysis coupled with laser Doppler flowmetry in cohort studies aimed at
      studying microvascular dysfunction in patients with microvascular diseases.

PMID- 17229424
TI  - Regulation of ezrin localization by Rac1 and PIPK in human epithelial cells.
AB  - Regulation of ezrin and other ERM proteins is not completely understood, but the
      involvement of Rho GTPases seems crucial. In this work, expression plasmids
      encoding full-length, deleted or truncated ezrin were constructed and coexpressed
      with Rac1 GTPase in HeLa human epithelial cells in order to elucidate the
      mechanisms of ezrin activation and function. We observed induction of actin
      stress fiber formation by ezrin constructs harboring the F-actin binding site but
      devoid of sequences required for intra- or intermolecular binding. Stress fiber
      inducing ezrin mutants were localized in adherens junctions containing N-cadherin
      but no E-cadherin, and also colocalized with F-actin in stress fibers. This
      localization required the activity of Rac1 and phosphatidylinositol-4-phosphate 5
      kinase and involved RhoA. We suggest that localization of ezrin in adherens
      junctions is regulated by Rac in a manner involving PIPK.

PMID- 17229425
TI  - Front-line management, staffing and nurse-doctor relationships as predictors of
      nurse and patient outcomes. a survey of Icelandic hospital nurses.
AB  - OBJECTIVE: To investigate aspects of nurses' work environments linked with job
      outcomes and assessments of quality of care in an Icelandic hospital. BACKGROUND:
      Prior research suggests that poor working environments in hospitals significantly
      hinder retention of nurses and high quality patient care. On the other hand,
      hospitals with high retention rates (such as Magnet hospitals) show supportive
      management, professional autonomy, good inter-professional relations and nurse
      job satisfaction, reduced nurse burnout and improved quality of patient care.
      METHODS: Cross-sectional survey of 695 nurses at Landspitali University Hospital,
      Reykjavik. Nurses' work environments were measured using the nursing work index
      revised (NWI-R) and examined as predictors of job satisfaction, the Maslach
      burnout inventory (MBI) and nurse-assessed quality of patient care using linear
      and logistic regression approaches. RESULTS: An Icelandic adaptation of the NWI-R
      showed a five-factor structure similar to that of Lake (2002). After controlling
      for nurses' personal characteristics, job satisfaction, emotional exhaustion and
      nurse rated quality of care were found to be independently associated with
      perceptions of support from unit-level managers, staffing adequacy, and nurse
      doctor relations. CONCLUSIONS: The NWI-R measures elements of hospital nurses'
      work environments that predict job outcomes and nurses' ratings of the quality of
      patient care in Iceland. Efforts to improve and maintain nurses' relations with
      nurse managers and doctors, as well as their perceptions of staffing adequacy,
      will likely improve nurse job satisfaction and employee retention, and may
      improve the quality of patient care.

PMID- 17229426
TI  - Efficacy and safety of rosuvastatin 40 mg versus atorvastatin 80 mg in high-risk
      patients with hypercholesterolemia: results of the POLARIS study.
AB  - POLARIS investigated the efficacy and safety of rosuvastatin 40 mg and
      atorvastatin 80 mg in high-risk patients with hypercholesterolemia. Patients
      (n=871) were randomized to rosuvastatin 40 mg/day or atorvastatin 80 mg/day for
      26 weeks. The primary endpoint was percentage change in LDL-C levels at 8 weeks.
      Secondary assessments included safety and tolerability, NCEP ATP III LDL-C goal
      achievement, change in other lipids and lipoproteins at 8 and 26 weeks, and
      health economics. Mean LDL-C levels were reduced significantly more with
      rosuvastatin 40 mg than with atorvastatin 80 mg at 8 weeks (-56% versus -52%,
      p<0.001). The proportion of patients achieving the NCEP ATP III LDL-C goal at 8
      weeks was significantly higher in the rosuvastatin 40 mg group (80% versus 72%,
      p<0.01). Significant differences in the change from baseline in high-density
      lipoprotein cholesterol (HDL-C) (+9.6% versus +4.4%) and apolipoprotein (Apo)A-I
      levels (+4.2 versus -0.5) were observed between rosuvastatin and atorvastatin
      (all p<0.05). Both treatments were well tolerated. Based on a US analysis,
      rosuvastatin used fewer resources and delivered greater efficacy. Intensive lipid
      lowering therapy with rosuvastatin 40 mg/day provided greater LDL-C-lowering
      efficacy than atorvastatin 80 mg/day, enabling more patients to achieve LDL-C
      goals. Rosuvastatin may therefore improve LDL-C goal achievement in high-risk
      patients with hypercholesterolemia.

PMID- 17229427
TI  - Predicting the subject-specific primary stability of cementless implants during
      pre-operative planning: preliminary validation of subject-specific finite-element
      models.
AB  - Pre-operative planning help the surgeon in taking the proper clinical decision.
      The ultimate goal of this work is to develop numerical models that allow the
      surgeon to estimate the primary stability during the pre-operative planning
      session. The present study was aimed to validate finite-element (FE) models
      accounting for patient and prosthetic size and position as planned by the
      surgeon. For this purpose, the FE model of a cadaveric femur was generated
      starting from the CT scan and the anatomical position of a cementless stem
      derived by a skilled surgeon using a pre-operative CT-based planning simulation
      software. In-vitro experimental measurements were used as benchmark problem to
      validate the bone-implant relative micromotions predicted by the patient-specific
      FE model. A maximum torque in internal rotation of 11.4 Nm was applied to the
      proximal part of the hip stem. The error on the maximum predicted micromotion was
      12% of the peak micromotion measured experimentally. The average error over the
      entire range of applied torques was only 7% of peak measurement. Hence, the
      present study confirms that it is possible to accurately predict the level of
      primary stability achieved for cementless stems using numerical models that
      account for patient specificity and surgical variability.

PMID- 17229428
TI  - Determination of trace levels of total fluorine in water using combustion ion
      chromatography for fluorine: a mass balance approach to determine individual
      perfluorinated chemicals in water.
AB  - Perfluorinated compounds (PFCs) such as perfluorooctanesulfonate (PFOS) and
      perfluorooctanoate (PFOA) have received worldwide attention because of their
      environmental persistence and widespread distribution. Because of the lack of
      robust analytical methods and standards to detect all of the PFCs, and their
      precursors and metabolic intermediates, a mass balance approach involving the
      determination of total fluorine (TF), followed by fractionation of samples to
      separately determine inorganic and organic fluorine, is needed. In this study, we
      have developed a method to determine low microg/L levels of total fluorine (TF)
      in seawater samples. Further, seawater samples were fractionated into organic and
      inorganic fractions by extraction with organic solvents, which were then analyzed
      for TF, extractable organic fluorine (EOF) and inorganic fluorine (IF; i.e.,
      fluoride). Concentrations of known perfluorinated compounds (PFCs) including PFOS
      and PFOA were also determined in water samples by liquid chromatography-tandem
      mass spectrometry (LC-MS/MS) to enable calculation of the fraction of fluorine
      that is contributed by PFCs to TF. A major proportion of fluorine in seawater was
      in the form of fluoride (>90% in locations not affected by direct discharges).
      Nevertheless, within the organofluorine fraction, a major percentage (60-90%) of
      fluorine still remains unknown in water samples, suggesting the occurrence of
      other fluorinated acids in addition to known perfluorinated acids. Further
      studies are needed to identify and quantify the unidentified organofluorines in
      seawater. Mass balance analysis of total organic fluorine (TOF) and EOF is
      important, if we are to understand transport and fate of fluorinated compounds in
      the environment, and if we are to identify the sources of unidentified
      fluorinated compounds.

PMID- 17229429
TI  - Development of a mass spectrometry method for the determination of a melanoma
      biomarker, 5-S-cysteinyldopa, in human plasma using solid phase extraction for
      sample clean-up.
AB  - 5-S-cysteinyldopa is a well-known pigment intermediate and analysis of its plasma
      concentration is interesting for the early diagnosis, as well as for evaluation
      of treatment and follow-up of malignant melanoma. A determination method of 5-SCD
      in human plasma was developed using solid phase extraction (SPE) on disposable
      cartridges and liquid chromatography electrospray mass spectrometry (LC-ESI-MS
      MS). Compound's sensitivity to light and oxidation requires the addition of anti
      oxidative agents (AO), to work in acidic media at 4 degrees C and to avoid light
      exposure of samples since blood collection. Different solid phases involving
      covalent binding to phenylboronic groups or dual retention mechanisms were
      evaluated and extraction cartridges containing both hydrophobic and strong cation
      exchange functionalities were finally selected. The LC separation of 5-SCD from
      endogenous catecholamines was achieved by gradient elution on a C18 stationary
      phase. 5-SCD was detected by multiple reaction monitoring (MRM) performed on
      ES(+) generated ions. Finally, the method was prevalidated in the lower ng/ml
      range. Good results with respect to accuracy, trueness and precision were
      obtained.

PMID- 17229430
TI  - Numerical determination of the adsorption isotherms of tryptophan at different
      temperatures and mobile phase compositions.
AB  - Single-component adsorption isotherm data were acquired by frontal analysis (FA)
      for tryptophan on a C(18)-Kromasil packed column, using acetonitrile-water
      solutions of various compositions (2.5, 5, and 7.5% ACN+1% acetic acid) and at
      five different temperatures between 25 and 65 degrees C. The adsorption isotherm
      model accounting best for these data is the bi-Moreau model, showing that two
      types of adsorption sites coexist on the surface and that strong adsorbate
      adsorbate interactions take place. Large concentration band profiles of
      tryptophan were obtained for the three mobile phase compositions, at five
      different temperatures and the best values of the adsorption isotherm
      coefficients were determined by the inverse method (IM) of chromatography. The
      advantages and drawbacks of using the FA and the IM for determining the
      coefficients of the adsorption isotherm of tryptophan under the experimental
      conditions selected are discussed. The results of the FA and IM measurements are
      in good agreement. Both indicate that the retention time of tryptophan decreases
      rapidly with increasing acetonitrile concentration in the mobile phase as well as
      the saturation capacities of the two types of adsorption sites, with the highest
      values of the two saturation capacities being found for the lowest ACN content
      and the lowest temperature. The adsorption constant on the low-energy sites
      decreases with increasing acetonitrile content and temperature. In contrast, the
      adsorption constant on the high-energy sites increases with increasing ACN
      content of the mobile phase but decreases with increasing temperature. The solute
      solute interaction parameters for the low and the high-energy adsorption sites
      increase rapidly with increasing ACN concentration in the mobile phase and with
      increasing temperature.

PMID- 17229431
TI  - Free flow isotachophoresis in an injection moulded miniaturised separation
      chamber with integrated electrodes.
AB  - An injection moulded free flow isotachophoresis (FFITP) microdevice with
      integrated carbon fibre loaded electrodes with a separation chamber of 36.4mm
      wide, 28.7 mm long and 100 microm deep is presented. The microdevice was
      completely fabricated by injection moulding in carbon fibre loaded polystyrene
      for the electrodes and crystal polystyrene for the remainder of the chip and was
      bonded together using ultrasonic welding. Two injection moulded electrode designs
      were compared, one with the electrode surface level with the separation chamber
      and one with a recessed electrode. Separations of two anionic dyes, 0.2mM each of
      amaranth and acid green and separations of 0.2mM each of amaranth, bromophenol
      blue and glutamate were performed on the microdevice. Flow rates of 1.25 ml min(
      1) for the leading and terminating electrolytes were used and a flow rate of 0.63
      ml min(-1) for the sample. Electric fields of up to 370 V cm(-1) were applied
      across the separation chamber. Joule heating was not found to be significant
      although out-gassing was observed at drive currents greater than 3 mA.

PMID- 17229432
TI  - Determination of isopropyl-9H-thioxanthen-9-one in packaged beverages by solid
      phase extraction clean-up and liquid chromatography with tandem mass spectrometry
      detection.
AB  - A simple method was developed and validated for the trace determination of 2
      isopropylthioxanthone (ITX) in packaged drinks. Samples were extracted from the
      food matrix using acetonitrile:water (60:40, v/v), and further subjected to clean
      up and preconcentration using solid-phase extraction prior to analysis by liquid
      chromatography-tandem mass spectrometry using multiple reaction monitoring (MRM)
      mode. The use of 2-isopropyl-[(2)H7]thioxanthen-9-one was incorporated into the
      method as an internal standard. Excellent 3-day interday precision data (RSD
      0.72%, n=10), and intraday precision data (RSD 0.52%, n=10) were obtained on a
      0.10 microg/L standard solution. Spiked samples (n=8) were used to gauge the
      accuracy of the method at the concentration levels of 2.5, 100, and 500 microg/kg
      in food; recoveries ranged from 97.0 to 103.0%. These excellent validation data
      suggest the exciting possibility of using this method for the determination of
      low levels of ITX migrating from printed food packaging materials into beverages
      with a method quantitation limit of 0.50 microg/kg. For the first time, analysis
      on a range of milk, juice, tea and yoghurt drinks, as well as their respective
      food packaging materials were performed for comparative studies on their ITX
      content.

PMID- 17229433
TI  - Separation and investigation of structure-mobility relationship of gonadotropin
      releasing hormones by capillary zone electrophoresis in conventional and
      isoelectric acidic background electrolytes.
AB  - Capillary zone electrophoresis (CZE) has been applied to qualitative and
      quantitative analysis, separation and physicochemical characterization of
      synthetic gonadotropin-releasing hormones (GnRHs) and their analogs and
      fragments. Structurally related peptides were separated in conventional and
      isoelectric acidic background electrolytes (BGEs), pH 2.18-2.50. Best separation
      was achieved in isoelectric BGE composed of 200 mM iminodiacetic acid, pH 2.32.
      The effective electrophoretic mobilities, m(ep), of GnRHs in five BGEs were
      determined and four semiempirical models correlating effective mobility with
      charge, q, and relative molecular mass, M(r), (m(ep) versus q/M(r)(k), where k is
      related to the molecular shape) were tested to describe the migration behavior of
      GnRHs in CZE. None of the models was found to be quite definitively applicable
      for the whole set of 10 GnRHs differing in size (tetrapeptide-decapeptide) and
      positive charge (0.91-3.00 elementary charges). Nevertheless, for the dependence
      of m(ep) on q/M(r)(k), the highest coefficient of correlation, R=0.995-0.999, was
      obtained for k close to the value 0.5 in all five acidic BGEs. This indicates
      that the most probable structure of GnRHs in these BGEs can be predicted as a
      random coil.

PMID- 17229434
TI  - The interconnection between the surface tension and fluctuations within fine
      drops, bubbles, and their nuclei.
AB  - We consider the effect of surface tension upon fluctuations within the core of
      drops and bubbles. We also investigate the fluctuations of the substance density
      rho, volume V, and particle number N within the objects under study. It is
      demonstrated that cores of drops and bubbles are homogeneous when they contain
      several thousand nanoparticles (molecules, atoms). Fluctuations of particle
      number are very large within the nucleus core containing only a few
      nanoparticles. Therefore, the surface tension has a probabilistic character since
      there is no surface separating the nucleus substance from the surrounding medium,
      only a transitional zone whose radius fluctuates considerably in time. In this
      case, it is more correct to consider not the surface tension but a certain
      quantity that we named the quasi surface tension.

PMID- 17229435
TI  - Reverse micelle synthesis of rhodium nanoparticles.
AB  - Water-in-oil reverse micelles of butyl ammonium laurate in hexanes that contain
      sodium hexachlororhodate were reduced with sodium borohydride to yield rhodium
      nanoparticles. The size of the micelle, determined by dynamic light scattering,
      was from 3 to 20 nm and varied as the water to surfactant ratio (W) was changed.
      The rhodium nanoparticles exhibited a Gaussian size distribution (sigma=0.35 nm),
      with average diameters of 1.5, 2.2, and 2.9 nm. The products were characterized
      with TEM, HRTEM, and X-ray photoemission spectroscopy.

PMID- 17229436
TI  - Hydration of a Na(+)-montmorillonite studied by thermally stimulated
      depolarization current.
AB  - Thermally stimulated depolarization current (TSDC) technique is a powerful tool
      for probing dipole re-orientational motions in condensed matter. In the case of
      cation-exchangeable aluminosilicates, it allows the assessment of the potential
      barrier related to the hopping mechanism of cations and, consequently, the
      measurement of its evolution when molecules, i.e. water, are adsorbed and
      interact with the cations embedded in the solid framework. Then, using suitable
      models based on thermodynamics, the analysis of TSDC signals obtained at various
      hydration states provides insights about the surface properties of the studied
      solid and the mechanism of adsorption at the cationic site. In this work, TSDC is
      used to study the first stage, i.e. when the number of adsorbed molecules is
      below the occurrence of the water monolayer, of water adsorption in a Na(+)
      montmorillonite from Mostaganem (Algeria). It is shown that the hydration process
      follows two stages. Using the "chemical force" concept it can then be concluded
      that when the number of adsorbed water molecules per cation is lower than 2,
      cation-water interaction dominates the energetics of adsorption, whereas at
      higher water loading the water "chemical force" is also involved into water-water
      and/or water-clay framework interactions. The number of water molecules for the
      monohydrated state is found to be about 7.

PMID- 17229437
TI  - Transduction of the anti-apoptotic PTD-FNK protein improves the efficiency of
      transplantation of bone marrow mononuclear cells.
AB  - Since most transplanted cells rapidly die in an ischemic environment by hypoxia
      and hyponutrition, it is crucial to know how to protect transplanted cells for
      improving transplantation efficiency. We examined whether the transduction of an
      artificial anti-cell death protein (PTD-FNK) into bone marrow mononuclear cells
      (BM-MNCs) prevents cell death and improves the transplantation efficiency of BM
      MNCs in ischemic regions. Rat bone marrow cells were prepared from the femur and
      tibia and cultured on dishes precoated with human fibronectin in the absence of
      serum. BM-MNCs transduced with PTD-FNK survived better than those without the
      protein (P<0.008) and retained the potential to differentiate into endothelial
      progenitor cells (EPCs), as judged by the uptake of an acetylated low-density
      lipoprotein and the ability to bind lectin. Next, we used a co-culture system
      comprising human umbilical vein endothelial cells (HUVECs) and fibroblasts to
      examine angiogenic potential. HUVECs pretreated with PTD-FNK survived and formed
      a blood-vessel-like structure better than untreated cells (P<0.001). When BM-MNCs
      expressing EGFP were transplanted into ischemic areas of a male rat ischemic
      hindlimb model, the cells pretreated with PTD-FNK were incorporated into blood
      vessel with a higher efficiency than the untreated BM-MNCs (P=0.03). BM-MNCs
      protected through transduction of PTD-FNK maintained their angiogenic potential.
      Thus, PTD-FNK improves the transplantation efficiency of BM-MNCs into ischemic
      regions.

PMID- 17229438
TI  - Structure of dimeric SecA, the Escherichia coli preprotein translocase motor.
AB  - SecA is the preprotein translocase ATPase subunit and a superfamily 2 (SF2) RNA
      helicase. Here we present the 2 A crystal structures of the Escherichia coli SecA
      homodimer in the apo form and in complex with ATP, ADP and adenosine 5'
      [beta,gamma-imido]triphosphate (AMP-PNP). Each monomer contains the SF2 ATPase
      core (DEAD motor) built of two domains (nucleotide binding domain, NBD and
      intramolecular regulator of ATPase 2, IRA2), the preprotein binding domain (PBD),
      which is inserted in NBD and a carboxy-terminal domain (C-domain) linked to IRA2.
      The structures of the nucleotide complexes of SecA identify an interfacial
      nucleotide-binding cleft located between the two DEAD motor domains and residues
      critical for ATP catalysis. The dimer comprises two virtually identical protomers
      associating in an antiparallel fashion. Dimerization is mediated solely through
      extensive contacts of the DEAD motor domains leaving the C-domain facing outwards
      from the dimerization core. This dimerization mode explains the effect of
      functionally important mutations and is completely different from the
      dimerization models proposed for other SecA structures. The repercussion of these
      findings on translocase assembly and catalysis is discussed.

PMID- 17229439
TI  - Cross-reactivity studies of an anti-Plasmodium vivax apical membrane antigen 1
      monoclonal antibody: binding and structural characterisation.
AB  - Apical membrane antigen 1 (AMA1) has an important, but as yet uncharacterised,
      role in host cell invasion by the malaria parasite, Plasmodium. The protein,
      which is quite conserved between Plasmodium species, comprises an ectoplasmic
      region, a single transmembrane segment and a small cytoplasmic domain. The
      ectoplasmic region, which can induce protective immunity in animal models of
      human malaria, is a leading vaccine candidate that has entered clinical trials.
      The monoclonal antibody F8.12.19, raised against the recombinant ectoplasmic
      region of AMA1 from Plasmodium vivax, cross-reacts with homologues from
      Plasmodium knowlesi, Plasmodium cynomolgi, Plasmodium berghei and Plasmodium
      falciparum, as shown by immunofluorescence assays on mature schizonts. The
      binding of F8.12.19 to recombinant AMA1 from both P. vivax and P. falciparum was
      measured by surface plasmon resonance, revealing an apparent affinity constant
      that is about 100-fold weaker for the cross-reacting antigen when compared to the
      cognate antigen. Crystal structure analysis of Fab F8.12.19 complexed to AMA1
      from P. vivax and P. falciparum shows that the monoclonal antibody recognises a
      discontinuous epitope located on domain III of the ectoplasmic region, the major
      component being a loop containing a cystine knot. The structures provide a basis
      for understanding the cross-reactivity. Antibody contacts are made mainly to main
      chain and invariant side-chain atoms of AMA1; contact antigen residues that
      differ in sequence are located at the periphery of the antigen-binding site and
      can be accommodated at the interface between the two components of the complex.
      The implications for AMA1 vaccine development are discussed.

PMID- 17229440
TI  - Structure-function analysis of a bacterial deoxyadenosine kinase reveals the
      basis for substrate specificity.
AB  - Deoxyribonucleoside kinases (dNKs) catalyze the transfer of a phosphoryl group
      from ATP to a deoxyribonucleoside (dN), a key step in DNA precursor synthesis.
      Recently structural information concerning dNKs has been obtained, but no
      structure of a bacterial dCK/dGK enzyme is known. Here we report the structure of
      such an enzyme, represented by deoxyadenosine kinase from Mycoplasma mycoides
      subsp. mycoides small colony type (Mm-dAK). Superposition of Mm-dAK with its
      human counterpart's deoxyguanosine kinase (dGK) and deoxycytidine kinase (dCK)
      reveals that the overall structures are very similar with a few amino acid
      alterations in the proximity of the active site. To investigate the substrate
      specificity, Mm-dAK has been crystallized in complex with dATP and dCTP, as well
      as the products dCMP and dCDP. Both dATP and dCTP bind to the enzyme in a
      feedback-inhibitory manner with the dN part in the deoxyribonucleoside binding
      site and the triphosphates in the P-loop. Substrate specificity studies with
      clinically important nucleoside analogs as well as several phosphate donors were
      performed. Thus, in this study we combine structural and kinetic data to gain a
      better understanding of the substrate specificity of the dCK/dGK family of
      enzymes. The structure of Mm-dAK provides a starting point for making new anti
      bacterial agents against pathogenic bacteria.

PMID- 17229441
TI  - Does botulinum toxin decrease frequency and severity of sialorrhea in Parkinson's
      disease?
AB  - This study analysed if botulinum toxin type A (BTX-A) decreases drooling in 21
      Parkinson's disease patients. BTX-A injections were given in the parotid glands.
      The severity of drooling decreased in 18 (86%) patients, while frequency was
      reduced in 8 (38%). In 11(52%) patients, the frequency of drooling remained
      constant, which may reflect more difficulties in swallowing, compared to the
      group that presented such improvement. Future trials assessing the level of
      swallowing dysfunction may be important to establish a prognosis for patients who
      keep the frequency of drooling in spite of decreased severity after BTX
      injection.

PMID- 17229442
TI  - MK-801 alters diaphragmatic activities in unanesthetized rats differently between
      normoxia and hypoxia.
AB  - This study was designed to examine how systemic administration of an N-methyl-d
      aspartate (NMDA) receptor antagonist, MK-801, altered respiratory timing in
      unanesthetized rats under normoxia and hypoxia. To detect fine changes in
      inspiratory time (TI) and expiratory time (TE), and cycle duration (TTOT), we
      prepared a diaphragmatic electromyogram (EMGdia). Diaphragm electrodes and
      arterial and venous catheters were inserted into Wistar rats (n = 8) under
      pentobarbital anesthesia. The next day, EMGdia was recorded before and after
      intravenous administration of MK-801 (3 mg/kg) under normoxia and hypoxia (12%
      O2) without anesthesia, and the respiratory timing (TI, TE, TTOT), respiratory
      frequency (fR), and amplitude of the integrated EMGdia were measured. Arterial
      blood gases (ABGs), mean arterial pressure (MAP), and heart rate (fH) were also
      measured with the EMGdia. Under normoxia, MK-801 increased fR owing to a
      significant decrease in TE, and elevated both MAP and fH. Under hypoxia, MK-801
      suppressed an increase in fR owing to a significant increase in TI, and did not
      accelerate fH. In both gaseous conditions, on ABGs, MK-801 did not alter partial
      pressure of O2 (PaO2) or CO2 (PaCO2), and slightly decreased pH (but not less
      than 7.4). MK-801 significantly decreased hypoxic response (%change from
      normoxia) in fR, and increased that in EMGdia amplitude, and did not alter a
      total ventilatory index (fRxEMGdia amplitude). The results suggest that an NMDA
      receptor-mediated mechanism partially determines fR through significant
      alterations in respiratory timing, particularly in which the hypoxic ventilatory
      response was obtained in unanesthetized rats.

PMID- 17229443
TI  - Apoptosis in sulfur mustard treated A549 cell cultures.
AB  - The chemical warfare agent sulfur mustard (SM) is a strong alkylating agent that
      leads to erythema and ulceration of the human skin several hours after exposure.
      Although SM has been intensively investigated, the cellular mechanisms leading to
      cell damage remain unclear. Apoptosis, necrosis and direct cell damage are
      discussed. In this study we investigated apoptotic cell death in pulmonary A549
      cells exposed to SM (30-1000 microM, 30 min). 24 h after SM exposure DNA breaks
      were stained with the TUNEL method. Additionally, A549 cells were lysed and
      cellular protein was transferred to SDS page and blotted. Whole PARP as well as
      PARP cleavage into the p89 fragment, an indicator of apoptosis, were detected by
      specific antibodies. SM concentration dependent increase in TUNEL positive cells
      and PARP cleavage showed that SM is an inducer of apoptosis. It has been
      previously suggested that AChE is activated during apoptotic processes and may be
      involved in apoptosis regulation. Therefore, we examined AChE activity in A549
      cells upon induction of apoptosis by SM (100-500 microM). Increased AChE activity
      was found in SM treated A549 cell cultures examined as determined by the Ellman's
      assay and by western blot. AChE activity showed a strong correlation with TUNEL
      positive cells. However, the broad caspase inhibitor zVAD and the PARP-inhibitor
      3-aminobenzamide had no protective effect on A459 cells measured with AChE
      activity and frequency of TUNEL positive cells. In summary, our studies
      demonstrate that AChE activity may be a potential marker of apoptosis in A549
      cells after SM injury. To what extent AChE is involved in apoptosis regulation
      during SM poisoning has to be further investigated.

PMID- 17229445
TI  - Differential role of the 5-HT1A receptor in aggressive and non-aggressive mice:
      an across-strain comparison.
AB  - Differential role of the 5-HT(1A) receptor in aggressive and non-aggressive mice:
      an across-strain comparison. PHYSIOL BEHAV 00(0) 000-000, 2006. According to the
      serotonin (5-HT)-deficiency hypothesis of aggression, highly aggressive
      individuals are characterized by low brain 5-HT neurotransmission. Key regulatory
      mechanisms acting on the serotonergic neuron involve the activation of the
      somatodendritic inhibitory 5-HT(1A) autoreceptor (short feedback loop) and/or the
      activation of postsynaptic 5-HT(1A) receptors expressed on neurons in cortico
      limbic areas (long feedback loop). In this study, we examined whether low
      serotonin neurotransmission is associated with enhanced 5-HT(1A) (auto)receptor
      activity in highly aggressive animals. Male mice (SAL-LAL, TA-TNA, NC900-NC100)
      obtained through different artificial-selection breeding programs for aggression
      were observed in a resident-intruder test. The prefrontal cortex level of 5-HT
      and its metabolite 5-HIAA were determined by means of HPLC. The activity of the 5
      HT(1A) receptors was assessed by means of the hypothermic response to the
      selective 5-HT(1A) agonists S-15535 (preferential autoreceptor agonist) and 8
      OHDPAT (full pre- and postsynaptic receptor agonist). Highly aggressive mice had
      lower serotonin levels in the prefrontal cortex and two out of three aggressive
      strains had higher 5-HT(1A) (auto)receptor sensitivity. The results strengthen
      the validity of the serotonin-deficiency hypothesis of aggression and suggest
      that chronic exaggerated activity of the 5-HT(1A) receptor may be a causative
      link in the neural cascade of events leading to 5-HT hypofunction in aggressive
      individuals.

PMID- 17229446
TI  - Editorial: membrane and nuclear steroid hormone receptors: two integrated arms of
      the same signaling pathway?

PMID- 17229444
TI  - Nicotine potentiates the neurogenic contractile response of rabbit bladder tissue
      via nicotinic acetylcholine receptors: nitric oxide and prostaglandins have no
      role in this process.
AB  - Nicotine, a nicotinic acetylcholine receptors (nAChRs) agonist, has a role in
      modulation of the neurotransmitter release following nerve stimulation in both
      the central and peripheral nervous systems. The aim of this study was to
      determine whether electrical field stimulation (EFS)-evoked contractions are
      altered in rabbit bladder in the presence of nicotine and, if an alteration
      occurs, to investigate the effects of nitric oxide and prostaglandins on nicotine
      induced alternation in isolated rabbit bladder. EFS-evoked contractile responses
      from rabbit bladder obtained were recorded with isometric force displacement
      transducers. Nicotine was added to preparations at various concentrations. The
      effects of hexamethonium, cadmium (Cd(2+)), indomethacin and N-nitro-L-arginine
      methyl ester (L-NAME) were tested on the EFS-evoked contractions in the presence
      of nicotine. Nicotine led to a dose-dependent increase in the amplitude of the
      EFS-evoked contractile responses. Cd(2+) and hexamethonium inhibited the nicotine
      induced increase in EFS-evoked responses, whereas indomethacin and L-NAME had no
      effect. In conclusion, nicotine increased the EFS-evoked contractile responses
      possibly by facilitating release of neurotransmitters from nerve terminals by a
      mechanism dependent on the influx of Ca(2+) from voltage-gated Ca(2+) channels
      (VGCCs) via activation of nAChRs in isolated rabbit bladder. Nitric oxide and
      prostaglandins do not have a physiological role in the regulation of
      neurotransmitter release.

PMID- 17229447
TI  - How to compute the effective size of spatiotemporally structured populations
      using separation of time scales.
AB  - Calculations to derive effective population size become highly complicated when
      complex population structure is considered. We provide an easy method of
      computing the effective size of a subdivided population with overlapping
      generations (a spatiotemporally structured population) using an approximation
      based on separation of time scales. We also numerically compute the effective
      size to verify the accuracy of the derived formula. Various interesting
      quantities, including moments of coalescent time, are readily derived using this
      approach.

PMID- 17229448
TI  - The effect of centaurein on interferon-gamma expression and Listeria infection in
      mice.
AB  - We previously found that centaurein enhanced IFN-gamma transcription in T cells.
      Here, we demonstrate that centaurein increased the IFN-gamma expression in T and
      NK cells and the serum IFN-gamma level in mice. Centaurein elevated the
      transcription of T-bet but not GATA-3, which is consistent with its effect on
      that of IFN-gamma but not IL-4. Additionally, centaurein effectively protected
      mice against Listeria infection. Moreover, centaurein per se or in combination
      with antibiotics could treat Listeria infection. Our mechanistic studies suggest
      that centaurein augments IFN-gamma expression via a transcriptional up-regulation
      of T-bet and that centaurein protects against or treats Listeria infection via a
      modulation of IFN-gamma expression.

PMID- 17229450
TI  - The application of bioluminescence assay with culturing for evaluating
      quantitative disinfection performance.
AB  - Various methods, including bioluminescence assay, were investigated regarding
      their suitability for quantitatively evaluating the disinfection performance.
      Although bioluminescence assay itself has been widely reported as a rapid, easy
      and suitable method for analyzing live microorganisms, the limited sensitivity of
      its measurement (approximately 10(3)-10(4)cells/assay vial), which is
      insufficient for disinfection study, requires further study. Among three methods
      (amplifying by enzymatic method, membrane filtration, and amplification by
      culturing) examined for increasing the detection sensitivity, amplification by
      culturing showed the best performance as Escherichia coli was employed as an
      indicating microorganism. Even with a short culturing time of 4h, the detection
      limit of E. coli measurement was successfully improved 200-fold, and the
      analytical results were not dependent upon the state of E. coli growth
      (stationary state with E. coli stock suspension vs. growth state with E. coli).
      In addition, the analytical integrity of bioluminescence assay with culturing was
      further demonstrated in comparison with spread plate method as free chlorine and
      UV irradiation were employed in the disinfection study.

PMID- 17229449
TI  - Modulation of aflatoxin toxicity and biomarkers by lycopene in F344 rats.
AB  - Modulation by lycopene of aflatoxin B(1) (AFB(1))-induced toxic effects,
      metabolism, and metabolic activations was studied in young F344 rats. Animals
      were pretreated orally with either corn oil (control group) or lycopene [100
      mg/kg body weight (b.w.), intervention group] 5 days/week for 2 weeks. Control
      animals were then treated daily with AFB(1) (250 microg/kg b.w) alone.
      Intervention animals were administered lycopene (100 mg/kg b.w.) at 1 h following
      a daily treatment with AFB(1) (250 mug/kg b.w.). Pretreatment and intervention
      with lycopene significantly reduced the toxic effect caused by AFB(1) and greatly
      modulated AFB(1) metabolism and metabolic activation. Urinary excretion of AFB(1)
      phase 1 metabolites, AFM(1), AFQ(1), and AFP(1), was significantly decreased in
      lycopene-treated animals. Formation of serum AFB(1)-albumin adducts was also
      significantly reduced. The rate of reduction was from approximately 30% on day 1
      (p<0.05) to 67.7% on day 15 (p<0.001). Lycopene intervention also significantly
      reduced formation of AFB(1)-DNA adducts in liver compared to control animals,
      with the highest reduction (52.7%) occurring on day 3 (p<0.05). Levels of AFB(1)
      N(7)-guanine excreted in urine were also significantly decreased. Urinary
      excretion of the phase 2 detoxification metabolite, AFB(1)-mecapturic acid, was
      significantly increased in lycopene-intervened animals. AFB(1)-induced urinary
      excretion of 8-hydroxydeoxyguanosine was also reduced to 50% on day 7 after
      lycopene intervention. Collectively, these results suggest that inhibition of
      phase 1 metabolism and metabolic activation, as well as induction of phase 2
      detoxification enzyme activity are the potential mechanisms for the
      chemopreventive effects of lycopene.

PMID- 17229451
TI  - Biodegradation of distillery spent wash in anaerobic hybrid reactor.
AB  - A lab-scale anaerobic hybrid (combining sludge blanket and filter) reactor was
      operated in a continuous mode to study anaerobic biodegradation of distillery
      spent wash. The study demonstrated that at optimum hydraulic retention time
      (HRT), 5 days and organic loading rate (OLR), 8.7kgCOD/m(3)d, the COD removal
      efficiency of the reactor was 79%. The anaerobic reduction of sulfate increases
      sulfide concentration, which inhibited the metabolism of methanogens and reduced
      the performance of the reactors. The kinetics of biomass growth i.e. yield
      coefficient (Y,0.0532) and decay coefficient (K(d), 0.0041d(-1)) was obtained
      using Lawrence and McCarty model. However, this model failed in determining the
      kinetics of substrate utilization. Bhatia et al. model having inbuilt provision
      of process inhibition described the kinetics of substrate utilization, i.e.
      maximum rate of substrate utilization (R,1.945d(-1)) and inhibition coefficient
      values (K(i),0.032L/mg). Modeling of the reactor demonstrated that Parkin and
      Speece, and Bhatia et al. models, both, could be used to predict the effluent
      substrate concentration. However, Parkin and Speece model predicts effluent COD
      more precisely (within +/-2%) than Bhatia et al. model (within +/-5-20%) of the
      experimental value. Karhadkar et al. model predicted biogas yield within +/-5% of
      the experimental value.

PMID- 17229452
TI  - Thermophilic aerobic granular biomass for enhanced settleability.
AB  - Aerobic biological wastewater treatment at thermophilic (ca. 55 degrees C)
      temperatures notoriously produces biomass that flocculates poorly or not at all.
      Contrary to this, thermophilic aerobic biomass that settled well in sequencing
      batch reactors was cultured with sludge volume index (SVI) values as low as
      60mL/g. A mixture of granular and flocculant biomass resulted when closed
      reactors were sparged with recirculated reactor headspace gas containing some
      air, whereas a conventionally aerated control reactor sparged with air alone
      contained dispersed growth that did not flocculate. Maximum granule diameter was
      from 1.2 to 1.9mm, and granule resistance to disintegration was comparable to
      aerobic mesophilic granules. Two bacteria were isolated and identified as
      Anoxybacillus flavothermus and Pseudoxanthomonas taiwanensis as determined by
      partial 16S rDNA sequencing. Anoxybacilli species are alkaliphilic or
      alkalitolerant, with the type species having an obligate requirement for
      carbonate, even when grown on glucose. We postulate that high alkalinity and
      CO(2) may select for a population of aerobic thermophilies that flocculates and
      granulates.

PMID- 17229453
TI  - Temporal and spatial variation of phosphate distribution in the sediment of a
      free water surface constructed wetland.
AB  - This study was aimed at determining the spatial and temporal variation of P
      distribution in sediment of an artificial wetland for sewage and industrial
      wastewater treatment, and the fraction that is potentially involved in the P
      exchange processes. Influent, effluent, macrophytes and sediment at the inlet,
      middle and outlet areas were sampled over 24 months. The P-fractionation in
      sediment was performed following the EDTA method. Eichhornia crassipes and Typha
      domingensis removed P efficiently when cover was high, but E. crassipes caused
      anoxic conditions. The increase in cover of T. domingensis may contribute to
      attain oxic conditions and to improve P removal. When macrophytes are not present
      or when cover is low, sediment seems to increase removal efficiency. A
      significant increase in the concentration of the fraction of Fe(OOH)
      approximately P and mainly that of CaCO(3) approximately P can be observed at the
      inlet. High pH, Ca(2+) and CO(3)(-)(2) concentrations in the influent suggest
      that P co-precipitates together with CaCO(3). Therefore, it seems that CaCO(3)
      approximately P represents the main precipitating mechanism. However,
      mineralization of organic matter maintained the sediment at a pH range lower than
      the high values prevailing in the influent. CO(3)(-)(2) could undergo partial
      dissolution and the released i-P(diss) could be readsorbed onto the Fe(OOH)
      approximately P fraction. Since the environment for P retention (high pH, Fe, Ca
      and ionic concentrations) is largely provided by the influent, the wetland may be
      expected to continue retaining P as far as the composition of the influent is
      maintained and there are available adsorption sites in the sediment.

PMID- 17229454
TI  - Trophic influences of metal accumulation in natural pollution laboratories at
      deep-sea hydrothermal vents of the Mid-Atlantic Ridge.
AB  - This study reports on the concentration of both, toxic (Hg) and essential (Fe,
      Cu, Zn) metals in representative species, at four hydrothermal vents along the
      Mid-Atlantic Ridge (MAR) corresponding to the different exposure conditions that
      are the result of contrasted geological setting and different depths along the
      ridge axis. Macro fauna collected from these vent sites showed markedly different
      whole tissue concentration of metals reflecting exposure levels. Bio-transfer of
      metals within a typical hydrothermal food chain was investigated. There were
      trophic level-specific variations in essential metal accumulation showing a
      general trend within which the secondary consumers (predators/scavengers) and
      primary consumers (filter-feeder/symbiont reliant species like the mixotrophic
      mollusks and sponges all having metal concentrations above those in passive
      suspension-feeders such as echinoderms, gorgonians) accumulated highest
      concentrations of all elements followed by primary producers such as endosymbiont
      bacteria. Mercury accumulation followed a somewhat different sequence among the
      same taxonomic groups: top concentrations in the symbiont-bearing filter-feeder
      bivalves >crustaceans> sponges > bacteria > echinoderms, gorgonians and
      tunicates. There were no indications of biomagnification of Hg, Cu and Zn unlike
      Fe that showed positive transference factors (TF) along two trophic levels of a
      typical chain at Menez Gwen.

PMID- 17229455
TI  - Nitrous oxide emissions from an intensively cultivated maize-wheat rotation soil
      in the North China Plain.
AB  - N2O emissions from a maize-wheat rotation field were monitored in the Fengqiu
      State Key Agro-Ecological Experimental Station (Fengqiu County, Henan Province,
      China) from June 2004 to June 2005. The experiment included four treatments: a
      bare (crop-absent) soil treated with 150 kg N ha-1 (WN150) and soils fertilized
      with 0 (N0), 150 (N150), and 250 (N250) kg N ha-1 and cropped with maize or
      wheat. The bulk of the N2O emissions occurred in pulses following the application
      of fertilizer N at soil temperatures of 15 degrees C or more. The application of
      fertilizer N significantly increased the N2O emission, from 636 g N2O-N ha-1 year
      1 in the N0 treatment to 4480 g N2O-N ha-1 year-1 in the N250 treatment. However,
      this increase primarily occurred during the maize growing season. The emission
      factor of applied fertilizer N as N2O was 1.05-1.34% and 0.24-0.26% during the
      105-day maize and 241-day wheat growing seasons, respectively, and was on average
      0.61-0.77%. Increasing the rate of fertilizer application increased the emission
      factor during the maize growing season. The presence of maize appears to increase
      N2O emission by 45% versus bare soil during the maize growing season. And, N2O
      emission during the maize season were significantly related to CO2 production
      (R=0.43-0.81, n=30, P<0.05). N2O emission was greatly affected by soil moisture
      during the maize growing season and by soil temperature during the wheat growing
      season. The maximum rates of nitrification occurred when soil moisture was in the
      range of 45-60% WFPS, with the optimum value being approximately 50%. However,
      soil moisture influenced N2O emission only when the soil temperature was at the
      optimum level. It is suggested that reducing the application rate of basal
      fertilizer N during the maize growing season could decrease N2O emission.

PMID- 17229456
TI  - Trace element accumulations in 13 avian species collected from the Kanto area,
      Japan.
AB  - In the present study, concentrations of 13 elements (Li, Cr, Mn, Cu, Zn, As, Se,
      Rb, Sr, Mo, Ag, Cd, Hg) were measured in the tissues of the livers, the kidneys,
      pectoral muscles, lungs and brains of 13 avian species collected from the Kanto
      area of Japan. The difference in hepatic heavy metal levels of the grey herons
      from the two sites was compared. Metal levels in the sediment of the Tama River
      estuary, situated in the Haneda area, were also measured. These results revealed
      that heavy metal pollution is present in an aquatic area of Haneda. The
      accumulation patterns of Cu and Zn in the livers of grey herons appeared to be
      separated into two groups. Additionally, the present study includes the
      properties of other metal accumulations and their relationships in avian species.

PMID- 17229457
TI  - Is exogenous tissue plasminogen activator necessary for antithrombotic efficacy
      of an inhibitor of thrombin activatable fibrinolysis inhibitor (TAFI) in rats?
AB  - INTRODUCTION: TAFI indirectly reduces the action of tPA on plasminogen. Whether
      exogenous tPA is necessary for TAFI inhibitor efficacy is unclear. Potato
      carboxypeptidase inhibitor (PCI), a TAFI inhibitor, has shown variable tPA
      dependence in rat models of arteriovenous shunt thrombosis (required) and
      microthrombosis (not required). This study was designed to further explore the
      importance of exogenous tPA in revealing PCI activity in rat models of venous and
      arterial thrombosis and provoked bleeding. METHODS: PCI was given as a bolus (5,
      10 mg/kg) +/- infusion (5, 10 mg/kg/h) and with or without low dose tPA (5, 10,
      25 microg/kg/min). In each instance tPA was adjusted to produce subthreshold
      thrombus reduction. Arterial thrombosis was induced by FeCl2; venous thrombosis
      by tissue factor or FeCl2. Bleeding was induced by kidney incision with PCI given
      (5 mg + 5 mg/kg/h) in the presence or absence of tPA (10, 150, 200
      microg/kg/min). RESULTS: PCI was ineffective without exogenous tPA in all tested
      thrombosis models. With exogenous tPA, PCI decreased thrombus weight 85% in
      tissue factor thrombosis, 59% in FeCl2 thrombosis, and 46% in arterial
      thrombosis. PCI prolonged bleeding only when combined with a relatively high tPA
      dose (200 microg/kg/min) that increased bleeding alone. CONCLUSIONS: If the
      current results predict clinical efficacy, the need for exogenous tPA in
      combination with TAFI inhibition is a potential problem. However, in acute
      settings where intravenous fibrinolytics are administered, or indications in
      which tPA production increases, TAFI inhibitors may prove to be safe and
      moderately effective profibrinolytic agents.

PMID- 17229458
TI  - Comparison of a rapid platelet function assay--Verify Now Aspirin--with whole
      blood impedance aggregometry for the detection of aspirin resistance.

PMID- 17229459
TI  - Macrophages, inflammation and risk of cervical intraepithelial neoplasia (CIN)
      progression--clinicopathological correlation.
AB  - OBJECTIVE: To evaluate the population of macrophages during the cervical
      malignant transformation and its influence in CIN outcome. METHODS: Biopsies from
      26 normal cervix, 28 low-grade (LSIL), 30 high grade squamous intraepithelial
      lesions (HSIL) and 28 squamous cell carcinomas (SCC) were stained by H&E to
      assess inflammation and by immunohistochemistry with anti-CD68 to detect
      macrophages. The macrophage count was corrected for the epithelial and stromal
      compartments using appropriate software. Clinical and prospective follow-up data
      were also available. RESULTS: We identified that macrophage count increased
      linearly with disease progression (median count per case at x200 magnification:
      normal, 5.1; LSIL, 5.5; HSIL, 9.9; SCC, 14.5; P<0.001), that inflammation also
      increased (moderate-intense inflammation present in 25%, 46.1%, 58.4% and 89.3%
      of normal, LSIL, HSIL and SCC, respectively; P<0.001) and that macrophage count
      was independently associated with the lesion grade (P<0.001). Moreover,
      macrophages showed an increasing migration into the epithelium along with the
      progression of CIN to invasive cancer. Of the 24 LSIL cases with information
      available, followed-up for 805+/-140 days, 16 regressed, 6 persisted and 2
      progressed. Age, high-risk HPV or inflammation were not risk factors for
      persistent/progressed LSIL in our cohort. However, LSIL that persisted or
      progressed showed a higher macrophage count (median of 10.8) than lesions that
      regressed (7; P=0.031). CONCLUSIONS: The study on macrophages offers a potential
      approach for cervical cancer treatment, since macrophages are closely related to
      progression of CIN, and can be used as an applicable marker of such a risk.

PMID- 17229461
TI  - Ovarian neuroendocrine carcinoma, non-small cell type, associated with serous
      carcinoma.
AB  - BACKGROUND: Neuroendocrine carcinoma of the non-small cell type of the ovary is a
      rare aggressive tumor, interestingly associated with either a surface epithelial
      tumor or teratoma. CASE: A 71-year-old woman presented with a pelvic mass and
      underwent a total abdominal hysterectomy with a bilateral salpingo-oophorectomy.
      Pathology examination showed a 6.5 cm in greatest dimension ovarian tumor
      composed of neuroendocrine carcinoma of the non-small cell type and serous
      carcinoma. Immunohistochemical studies including keratin 7, WT-1, and
      neuroendocrine markers demonstrated differences in the two components.
      Microsatellite instability (MSI) analysis using five polymorphic markers also
      showed a different pattern in the two components. CONCLUSION: This is the first
      report of an ovarian neuroendocrine carcinoma, non-small cell type, associated
      with a serous carcinoma. Immunohistochemistry and MSI are very helpful in making
      a definite diagnosis.

PMID- 17229460
TI  - The diagnostic value of PET/CT for primary ovarian cancer--a prospective study.
AB  - OBJECTIVES: To prospectively evaluate the diagnostic value of combined PET/CT in
      detecting a malignant tumor in patients with no previous cancer history,
      presenting with a pelvic mass. METHODS: From September 2004 to March 2006, 101
      patients (median age=60 years, range=24-85 years) with a Risk of Malignancy Index
      (RMI)>150 based on serum CA-125, ultrasound examinations (US) and menopausal
      state, were referred to PET/CT within 2 weeks prior to standard surgery/debulking
      of a pelvic tumor. Histological specimens from 97 patients were evaluated and the
      histological diagnoses were compared to the PET/CT results to calculate the
      diagnostic value of PET/CT in differentiating between malignant and
      borderline/benign tumors. Four patients refrained from surgery or biopsy.
      RESULTS: The average serum CA-125 in the 97 studied patients was 784 U/ml
      (range=22-9665 U/ml). PET/CT demonstrated areas of abnormally increased metabolic
      activity considered highly suspicious for malignant tumor in 60 patients (62%).
      In 37 patients (38%) the tumors were considered benign on PET/CT. Histopathology
      showed benign tumors in 40 patients and malignant tumors in 57 patients. The
      sensitivity and specificity for PET/CT in diagnosing a malignant pelvic tumor
      were 100% (57/57) and 92.5% (37/40), respectively (P<0.00005). CONCLUSION:
      Combined PET/CT demonstrates high diagnostic value in identifying primary ovarian
      cancer in patients with a pelvic mass of unknown origin and RMI>150. We suggest
      PET/CT as the image modality of choice when US shows a pelvic tumor and
      additional information prior to surgery is needed.

PMID- 17229462
TI  - Influence of different light curing units on the cytotoxicity of various dental
      composites.
AB  - OBJECTIVES: To evaluate the dependence of the toxicity of various dental
      composites on the use of high- and low-power light curing units (LCUs). METHODS:
      The composites Filtek Z 250, Durafill VS, Solitaire 2 and Grandio were
      polymerized using different light densities from three LCUs, namely Heliolux II,
      Swiss Master Light (SML) and a prototype LED. The toxicity of polymerized samples
      was tested by exposing them to the cell culture medium up to 28 days. The
      extracts of the composites were collected daily and used for incubation in human
      gingival fibroblasts cultures. RESULTS: Slow, low-intensity curing using the LED
      or the Heliolux II showed similar characteristics for all four composites,
      regarding the cell viability rate of human gingival fibroblasts. After 1 day of
      storage suboptimal results could be observed for the SML/Durafill and optimal
      results for SML/Grandio combination (approximately 100% cell viability). In
      addition, the composite Solitaire the SML yielded significantly better results
      than the other LCUs (cell viability, p < or = 0.001: SML 60.5%, Heliolux 44.5%,
      LED 44.2%). Furthermore, the combination of the SML with Z 250 composite showed,
      after the first day and up to day 28, statistically significantly higher cell
      viability rates than the combination with the LED or Heliolux II. SIGNIFICANCE:
      This study shows that the combination of a high power LCU with some composites
      positively influences the HGF cell viability effected by the investigated
      composite extracts. Moreover, there is further indication that a reduction of
      composite toxicity is possible if the curing mode is adapted to the used
      composite.

PMID- 17229463
TI  - Sex differences in the effect of acute tryptophan depletion on declarative
      episodic memory: a pooled analysis of nine studies.
AB  - Acute tryptophan depletion (ATD) studies have shown that serotonin plays a role
      in learning and memory processes. In this study, we performed a pooled analysis
      of nine ATD studies in order to examine the nature of the memory-impairing
      effects of ATD and mediating factors, such as gender, age and vulnerability for
      disease in which disturbed serotonin was hypothesized to play a role. All studies
      that were used in this pooled analysis assessed declarative episodic memory using
      a verbal learning task paradigm. Immediate recall, delayed recall, and delayed
      recognition scores were examined. A total of 211 participants were included in
      the analysis. The analysis revealed that ATD impaired not only delayed recall,
      but also immediate recall. The ATD-induced impairments were larger in females
      than in males. Furthermore, ATD did not interact with any other serotonergic
      vulnerability and age. This suggests that the only factor that actually has the
      properties of a serotonergic vulnerability factor for declarative memory
      performance is female gender. The findings provide further support for a critical
      role of serotonin in declarative episodic memory.

PMID- 17229465
TI  - Relationship between copy number of genes (C4A, C4B) encoding the fourth
      component of complement and the clinical course of hereditary angioedema (HAE).
AB  - In order to study if in patients with hereditary angioedema (HAE), copy number of
      the two genes (C4A and C4A) encoded in the central region of main
      histocompatibility complex (MHC) influences the diagnostically important C4 serum
      concentration as well as the clinical course of the disease, we determined copy
      number of the complement C4A and C4B genes in DNA samples of 95 HAE patients and
      246 healthy controls. Distribution of both the C4A and C4B copy numbers
      significantly (p=0.0183 and 0.0318, respectively) differed between the two
      groups, the most marked difference we observed was the lower frequency of the
      high (3 or 4) C4A copy numbers in the patients. As it expected, the dosage of
      both C4A and C4B genes positively correlated to the longitudinally measured serum
      C4 concentrations. Moreover, we found an unexpected clinical correlation with the
      dosage of the C4B gene. The course of the disease was milder in the 9/95 patients
      carrying 3 or 4 copies of C4B gene, compared to the rest of patients, i.e.
      diagnosis was established at significantly (p=0.0052) older age (36.0 (31.0
      39.5)) years versus 20.5 (7.5-31.5 years), bi-yearly attack rate was
      significantly (p=0.0145) lower (1.0 (0.0-11.0)) versus 11.0 (3.5-21.5), and the
      over-all activity of the classical pathway and the enzyme-inhibitor activity of
      the C1-inhibitor (C1-INH) was closer to the normal values. These observations
      indicate that high copy number of the C4B gene can be a protective factor against
      disease severity in HAE and therefore its determination is warranted.

PMID- 17229464
TI  - Differentiating the effects of fine and coarse particles on daily mortality in
      Shanghai, China.
AB  - The findings on health effects of ambient fine particles (PM2.5) and coarse
      particles (PM10-2.5) remain inconsistent. In China, PM2.5 and PM10-2.5 are not
      the criteria air pollutants, and their monitoring data are scarce. There have
      been no epidemiological studies of health effects of PM2.5 and PM10-2.5
      simultaneously in China. We conducted a time series study to examine the acute
      effects of PM2.5 and PM10-2.5 on daily mortality in Shanghai, China from Mar. 4,
      2004 to Dec. 31, 2005. We used the generalized additive model (GAM) with
      penalized splines to analyze the mortality, air pollution and covariate data. The
      average concentrations of PM2.5 and PM10-2.5 were 56.4 microg/m3 and 52.3
      microg/m3 in our study period, and PM2.5 constituted around 53.0% of the PM10
      mass. Compared with the Global Air Quality Guidelines set by World Health
      Organization (10 microg/m3 for annual mean) and U.S. National Ambient Air Quality
      Standards (15 microg/m3 for annual mean), the PM2.5 level in Shanghai was much
      higher. We found that PM2.5 was associated with the death rates from all causes
      and from cardiorespiratory diseases in Shanghai. We did not find a significant
      effect of PM10-2.5 on mortality outcomes. A10 microg/m3 increase in the 2-day
      moving average (lag01) concentration of PM2.5 corresponded to 0.36% (95% CI
      0.11%, 0.61%), 0.41% (95% CI 0.01%, 0.82%) and 0.95% (95% CI 0.16%, 1.73%)
      increase of total, cardiovascular and respiratory mortality. For PM10-2.5, the
      effects were attenuated and less precise. Our analyses provide the first
      statistically significant evidence in China that PM2.5 has an adverse effect on
      population health and strengthen the rationale for further limiting levels of
      PM2.5 in outdoor air in Shanghai.

PMID- 17229466
TI  - Melatonin receptors in the eye: location, second messengers and role in ocular
      physiology.
AB  - The pineal hormone melatonin, an important regulator of circadian and seasonal
      rhythms, has a role in ocular pathophysiology. In addition to the pineal gland,
      melatonin synthesis is carried out in several ocular structures. Moreover,
      specific melatonin receptors have been located in the retina, cornea, ciliary
      body, lens, choroid and sclera, which suggests that cells in these tissues may be
      targets for melatonin action. This review summarizes the current knowledge about
      melatonin receptor subtypes with the emphasis on those melatonin receptors, which
      have been identified in ocular tissues and their possible roles in biochemical
      and physiological processes in the eye.

PMID- 17229467
TI  - The physiological and pharmacological role of basic fibroblast growth factor in
      the dopaminergic nigrostriatal system.
AB  - Basic fibroblast growth factor (FGF-2) is a physiological relevant neurotrophic
      factor in the nigrostriatal system and hence a promising candidate for the
      establishment of alternative therapeutic strategies in Parkinson's disease. FGF-2
      and its high-affinity receptors (FGFR) display an expression in the developing,
      postnatal, and adult substantia nigra (SN) and in the striatum. Exogenous
      application promoted survival, neurite outgrowth and protection from neurotoxin
      induced death of dopaminergic (DA) neurons both in vitro and in vivo. In animal
      models of Parkinson's disease, co-transplantation of fetal DA cells with FGF-2
      expressing cells increased survival and functional integration of the grafted DA
      neurons resulting in improved behavioral performance. Analyzing the physiological
      function of the endogenous FGF-2 system during development and after neurotoxin
      induced lesion revealed for the DA neurons of the SNpc a dependence on FGFR3
      signaling during development. In addition, in the absence of FGF-2 an increased
      number of DA neurons was found, whereas enhanced levels of FGF-2 resulted in a
      reduced DA cell density. Following neurotoxin-induced lesion of DA neurons, FGF-2
      deleted mice displayed a higher extent of DA neuron death whereas in FGF-2
      overexpressing mice more DA neurons were protected. According to the data, FGF-2
      seems to promote DA neuron survival via FGFR3 during development, whereas absence
      of this ligand could be compensated by other members of the FGF family. In
      contrast, in the adult organism, FGF-2 cannot be compensated by other factors
      under lesion conditions suggesting a central role for this molecule in the
      nigrostriatal system.

PMID- 17229468
TI  - Bipolar spectrum disorders in severely obese patients seeking surgical treatment.
AB  - BACKGROUND: Much of the literature investigating the link between mood disorders
      and obesity has focused on depression whereas historic polarity of mood has not
      been previously carefully assessed. The aim of the present study has been to
      evaluate the prevalence of the entire bipolar spectrum, by including subsyndromal
      hypomania, and its related demographic and clinical correlates, in severely obese
      patients seeking surgical treatment. METHODS: Eighty-three consecutive bariatric
      patients who presented for presurgical psychiatric consultation were
      systematically interviewed with both the SCID-CV questionnaire and, as a self
      assessment instrument, with the Hypomania Symptom Checklist (HCL-32) on all past
      hypomanic behaviours (focusing more on prior overactivity than on mood changes)
      regardless of duration and initial negative response to the screening question on
      mood. RESULTS: A bipolar spectrum disorder was found in 89% of severely obese
      patients, with the highest prevalence rates for bipolar II disorder. Comorbidity
      with panic disorder was observed in 30% of bipolar spectrum patients.
      LIMITATIONS: The lack of normal-weight or general medical control groups and the
      reliance on self-report, retrospective assessment for the collection of some
      parameters warrant some caution in the interpretation of substantive findings.
      CONCLUSIONS: These findings suggest that bipolar spectrum illness, in particular
      a hypomanic condition characterized by overactivity, is very common in severely
      obese subjects, thus contradicting previous evidence of low levels of physical
      activity in this population. Given the high prevalence rates of bipolar spectrum
      in morbid obesity, this study encourages further research on the causal
      association.

PMID- 17229469
TI  - Open-label aripiprazole in the treatment of acute bipolar depression: a
      prospective pilot trial.
AB  - BACKGROUND: Increasing evidence indicates that some second-generation
      antipsychotics are efficacious in bipolar depression, but there are few data on
      this illness for the novel agent aripiprazole. METHODS: Aripiprazole response was
      prospectively assessed for 8 weeks with the Montgomery-Asberg Depression Rating
      Scale (MADRS), the Clinical Global Impression Scale Modified for Bipolar Illness
      (CGI-BP), and the Young Mania Rating Scale (YMRS) in 31 bipolar patients with
      acute depression inadequately responsive to 1 mood stabilizer. Side effects and
      body weight were also evaluated. Outcome measures were analyzed with repeated
      measures ANOVAs. RESULTS: Patients showed a significant decrease in mean MADRS
      total and CGI-BP-Depression Severity scores, but only 14 (45%) completed the 8
      week trial. Thirteen (42%) patients met criteria for response (> or =50%
      reduction in MADRS total score), 11 (35%) patients met criteria for remission
      (final MADRS total score < or =12), and 9 (29%) patients discontinued
      aripiprazole for side effects, most commonly akathisia (N=4). As a group,
      patients showed statistically insignificant weight gain (0.8+/-2.5 kg) over the 8
      week trial. CONCLUSION: Aripiprazole was associated with beneficial effects on
      mood in some patients with bipolar depression, but also had a high
      discontinuation rate, primarily due to side effects. Double-blind, placebo
      controlled studies are necessary to determine aripiprazole's efficacy,
      tolerability, and safety in bipolar depression.

PMID- 17229470
TI  - Specific antibody index in cerebrospinal fluid from patients with central and
      peripheral paraneoplastic neurological syndromes.
AB  - We evaluated the concentration of antineuronal antibodies in paired cerebrospinal
      fluid (CSF) and serum samples from 19 patients with central and peripheral
      paraneoplastic neurological syndromes (PNS), using an enzyme linked immunosorbent
      assay (ELISA) employing recombinant antineuronal antigens (HuD, Yo, Ri,
      CV2/CRMP5, amphiphysin, PNMA2/Ma2). The specific antibody index (AI) [Qspec/QIgG]
      was calculated to estimate specific intrathecal antibody synthesis. An AI>1.3 was
      considered as evidence of intrathecal specific antibody synthesis. 14 (88%) of 16
      patients with exclusive or predominant paraneoplastic involvement of the central
      nervous system (CNS) showed an AI>1.3, indicating a specific intrathecal antibody
      synthesis, while all three patients with isolated involvement of the peripheral
      nervous system showed an AI<0.8. All together, in 17 of 19 patients (89%) we
      found a significant association (p<0.05) between central or peripheral
      neurological manifestations on the one hand and presence or absence of specific
      intrathecal synthesis respectively on the other hand. These data support the
      hypothesis that autoimmunity is involved in the pathogenesis of PNS.

PMID- 17229471
TI  - Polychlorinated biphenyls induce proinflammatory cytokine release and
      dopaminergic dysfunction: protection in interleukin-6 knockout mice.
AB  - Proinflammatory cytokines are not only important mediators of brain development,
      but also pose an increased risk for neurodegeneration following exposure to
      neurotoxicants or trauma. We have used the ubiquitous environmental and
      occupational neurotoxicant polychlorinated biphenyls (PCBs) to investigate the
      putative role of inflammatory agents in mediating processes involved in basal
      ganglia dysfunctions. PCBs induced inflammatory responses in C57BL/6 adult male
      mice, significantly elevating serum levels of IL-6 (31%), IL-1beta (71%) and TNF
      alpha (22%) and significantly reducing striatal dopamine (DA, 21%), tyrosine
      hydroxylase (TH, 26%), dopamine transporter (DAT, 39%), and synaptophysin (29%)
      concentrations. We also exposed mice deficient in the proinflammatory cytokine
      interleukin-6 (IL-6-/-) to PCBs, to explore the role of this specific cytokine in
      mediating PCB-induced DA neurodegeneration. Not only did the PCB-treated IL-6-/-
      mice exhibit a decrease in serum levels of IL-1beta and TNF-alpha, but they were
      also protected from PCB-induced striatal dopaminergic dysfunction, displaying no
      signs of toxicant-induced reductions in DA levels, or TH, DAT or synaptophysin
      expression. Taken together, these results suggest that: (1) PCB exposure results
      in a peripheral inflammatory response associated with striatal terminal
      degeneration; and (2) the absence of IL-6 prevents PCB-induced dopaminergic
      losses in the striatum.

PMID- 17229472
TI  - Non-cognitive behaviours in an APP/PS1 transgenic model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterised by progressive cognitive impairment
      with neuropsychiatric symptoms such as anomalous motor behaviour, depression,
      anxiety, weight loss, irritability and agitation. The effect of hAPP and PS1
      overexpression on cognition has been well characterised in a variety of
      transgenic mouse models, however, non-cognitive behaviours have not been
      considered as systematically. The non-cognitive behaviour of the hAPP/PS1
      transgenic mouse model (TASTPM) was observed at ages spanning the rapid
      progression of amyloid neuropathology. TASTPM transgenic mice, of both genders,
      exhibited decreased spontaneous motor activity, disinhibition, increased
      frequency and duration of feeding bouts, reduced body weight and, by 10 months,
      increased activity over a 24h period. In addition to the aforementioned
      behaviours, male transgenic mice also displayed enhanced aggression relative to
      wildtype controls. These data reveal previously unreported disease relevant
      behavioural changes that demonstrate the value of measuring behaviour in APP/PS1
      transgenic models. These behavioural readouts could be useful in screening
      putative drug treatments for AD.

PMID- 17229473
TI  - Role of PI3K and PKB/Akt in acute natriuretic and NO-mimetic effects of leptin.
AB  - Apart from controlling energy balance, leptin, a peptide hormone secreted by
      white adipose tissue, is also involved in the regulation of cardiovascular
      function. Previous studies have documented that leptin stimulates natriuresis and
      nitric oxide (NO) production, but the mechanism of these effects is incompletely
      elucidated. We examined whether phosphoinositide 3-kinase (PI3K) and its
      downstream effector, protein kinase B/Akt are involved in acute natriuretic and
      NO-mimetic effects of leptin in anaesthetized rats. Leptin (1 mg/kg i.v.) induced
      a marked increase in natriuresis and this effect was abolished by pretreatment
      with either wortmannin (15 microg/kg) or LY294002 (0.6 mg/kg), two structurally
      different PI3K inhibitors. Moreover, leptin increased plasma concentration and
      urinary excretion of NO metabolites, nitrites+nitrates (NO(x)), and of NO second
      messenger, cyclic GMP. In addition, leptin increased NO(x) and cGMP in aortic
      tissue. The stimulatory effect of leptin on NO(x) and cGMP was prevented by
      PKB/Akt inhibitor, triciribine, but not by either wortmannin or LY294002.
      Triciribine had no effect on leptin-induced natriuresis. Leptin stimulated Akt
      phosphorylation at Ser(473) in aortic tissue but not in the kidney. These results
      suggest that leptin-induced natriuresis is mediated by PI3K but not Akt, whereas
      NO-mimetic effect of leptin results from PI3K-independent stimulation of Akt.

PMID- 17229474
TI  - Functional characterization of APOBEC-1 complementation factor phosphorylation
      sites.
AB  - ApoB mRNA editing involves site-specific deamination of cytidine 6666 producing
      an in-frame translation stop codon. Editing minimally requires APOBEC-1 and
      APOBEC-1 complementation factor (ACF). Metabolic stimulation of apoB mRNA editing
      in hepatocytes is associated with serine phosphorylation of ACF localized to
      editing competent, nuclear 27S editosomes. We demonstrate that activation of
      protein kinase C (PKC) stimulated editing and enhanced ACF phosphorylation in rat
      primary hepatocytes. Conversely, activation of protein kinase A (PKA) had no
      effect on editing. Recombinant PKC efficiently phosphorylated purified ACF64
      protein in vitro, whereas PKA did not. Mutagenesis of predicted PKC
      phosphorylation sites S154 and S368 to alanine inhibited ethanol-stimulated
      induction of editing suggesting that these sites function in the metabolic
      regulation of editing. Consistent with this interpretation, substitution of S154
      and S368 with aspartic acid stimulated editing to levels comparable to ethanol
      treatment in control McArdle RH7777 cells. These data suggest that
      phosphorylation of ACF by PKC may be a key regulatory mechanism of apoB mRNA
      editing in rat hepatocytes.

PMID- 17229477
TI  - The collateral pathway from the left internal thoracic artery to the left
      external iliac artery detected by multislice computed tomography.
AB  - It is important to evaluate the presence or absence of the collateral pathway
      from the left internal thoracic artery in aortoiliac occlusive disease. This case
      report indicates that multislice computed tomography is a very useful method for
      detecting this collateral pathway.

PMID- 17229476
TI  - Expression of a mutant p193/CUL7 molecule confers resistance to MG132- and
      etoposide-induced apoptosis independent of p53 or Parc binding.
AB  - p193/CUL7 is an E3 ubiquitin ligase initially identified as an SV40 Large T
      Antigen binding protein. Expression of a dominant interfering variant of mouse
      p193/CUL7 (designated 1152stop) conferred resistance to MG132- and etoposide
      induced apoptosis in U2OS cells. Immune precipitation/Western analyses revealed
      that endogenous p193/CUL7 formed a complex with Parc (a recently identified
      parkin-like ubiquitin ligase) and p53. Apoptosis resistance did not result from
      1152stop-mediated disruption of the endogenous p193/CUL7 binding partners.
      Moreover, 1152stop molecule did not directly bind to endogenous p193/CUL7, Parc
      or p53. These data suggested a role for p193/CUL7 in the regulation of apoptosis
      independently of p53 and Parc activity.

PMID- 17229478
TI  - Unveiling electrocardiographic mysteries.

PMID- 17229479
TI  - Comparison of CE-SSCP and DGGE for monitoring a complex microbial community
      remediating mine drainage.
AB  - Capillary electrophoresis single-strand conformation polymorphism (CE-SSCP) is a
      promising high-throughput tool for profiling complex bioremediation communities,
      but has not been well characterized with respect to other methods such as
      denaturing gradient gel electrophoresis (DGGE). The purpose of this study was to
      compare CE-SSCP with DGGE with respect to: 1) overall representation of the
      community in terms of the dominant species identified and corresponding Shannon
      diversity indices; 2) reproducibility and resolution; and 3) artifacts, using a
      complex sulfate-reducing community remediating mine drainage as a model system.
      Some of the dominant microorganisms were detected by both methods, but there were
      also differences in the reported community compositions, and more phylogenetic
      groups were detected by CE-SSCP. CE-SSCP Shannon diversity indices were slightly
      higher than those determined from DGGE data, and differed in terms of the time
      point at which the community was reported to have the highest diversity. Both
      methods had high reproducibility, but CE-SSCP resolution was higher in terms of
      the total number of peaks resolved, reduced co-migration of distinct DNA
      sequences, and length and legibility of the DNA sequencing data of clones used to
      identify peaks. Ten double bands in the same lane representing the same species
      were found by DGGE, whereas only one such artifact was observed by CE-SSCP.
      Finally, less overall sample preparation and analysis time was required for CE
      SSCP than for DGGE. The results suggest that CE-SSCP offers several advantages
      over DGGE, especially for high-throughput monitoring.

PMID- 17229480
TI  - Characterization of a Leuconostoc gelidum bacteriophage from pork.
AB  - A new bacteriophage (phage ggg) and its host, Leuconostoc gelidum LRC-BD, were
      isolated from vacuum-packaged pork loins. Homogenates of pork loin tissue were
      enriched with L. gelidum LRC-BD to isolate phages. Cultural, biochemical and
      genetic methods were used to compare L. gelidum LRC-BD and the type strain, L.
      gelidum ATCC 49366. The phages were characterized by host range, morphology and
      phage-bacterial interaction in All Purpose Tween (APT) broth and on pork adipose
      tissue. With the exception of its inability to produce dextran from sucrose and
      the fermentation of l-arabinose, L. gelidum LRC-BD was culturally and
      biochemically similar to L. gelidum ATCC 49366. DNA-relatedness of the strains
      was confirmed by sequencing of the 16s rRNA gene. Electron microscopic
      observation revealed that phage ggg was a member of the Siphoviridae. The host
      range was limited to L. gelidum isolates from meats. Phages were able to
      replicate and limit the growth of L. gelidum LRC-BD in APT broth incubated
      aerobically and anaerobically at 4 degrees C, with a multiplicity of infection
      (MOI) of 0.001. When inoculated pork adipose tissue was stored at 4 degrees C in
      air or vacuum, phages could multiply but a higher MOI (0.01 to 1000) was
      necessary to limit the growth of L. gelidum LRC-BD. Naturally occurring phages
      may affect the numbers of L. gelidum and other lactic acid bacteria residing in
      meats and thereby alter the storage quality or the preservative potential of
      competitive strains.

PMID- 17229481
TI  - Redox potential measurement as a rapid method for microbiological testing and its
      validation for coliform determination.
AB  - The redox potential is one of the most complex indicators of the physiological
      state of microbial cultures and its measurement could be a useful tool for the
      qualitative and quantitative determination of the microbial contamination. During
      the bacterial growth, the redox potential of the medium decreases. The shape of
      the redox potential curve is characteristic on the type of microorganism, and the
      rate of the change (dE/dt) is proportional to the living cell concentration.
      Defining the time required to reach a significant change in redox potential as
      Time to Detection (TTD), similarly to the impedimetric measurements, a strict
      linear correlation could be established between the TTD and the logarithm of the
      initial concentration of microorganisms. On the base of this calibration curve,
      the determination of living cell concentration could be simplified. For the
      experiments, a computer-controlled multi-channel measuring system and software
      was developed by the authors. The redox potential measurement method was tested
      and validated for the determination of coliform bacteria. The results have proved
      the high efficiency and reliability of the new method.

PMID- 17229482
TI  - CoryneRegNet 3.0--an interactive systems biology platform for the analysis of
      gene regulatory networks in corynebacteria and Escherichia coli.
AB  - CoryneRegNet is an ontology-based data warehouse for the reconstruction and
      visualization of transcriptional regulatory interactions in prokaryotes. To
      extend the biological content of CoryneRegNet, we added comprehensive data on
      transcriptional regulations in the model organism Escherichia coli K-12,
      originally deposited in the international reference database RegulonDB. The
      enhanced web interface of CoryneRegNet offers several types of search options.
      The results of a search are displayed in a table-based style and include a
      visualization of the genetic organization of the respective gene region.
      Information on DNA binding sites of transcriptional regulators is depicted by
      sequence logos. The results can also be displayed by several layouters
      implemented in the graphical user interface GraphVis, allowing, for instance, the
      visualization of genome-wide network reconstructions and the homology-based inter
      species comparison of reconstructed gene regulatory networks. In an application
      example, we compare the composition of the gene regulatory networks involved in
      the SOS response of E. coli and Corynebacterium glutamicum. CoryneRegNet is
      available at the following URL: http://www.cebitec.uni
      bielefeld.de/groups/gi/software/coryneregnet/.

PMID- 17229475
TI  - MAP kinase pathways: the first twenty years.
AB  - The MAP kinases, discovered approximately 20 years ago, together with their
      immediate upstream regulators, are among the most highly studied signal
      transduction molecules. This body of work has shaped many aspects of our present
      views of signal transduction by protein kinases. The effort expended in this area
      reflects the extensive participation of these regulatory modules in the control
      of cell fate decisions, i.e., proliferation, differentiation and death, across
      all eukaryotic phylla and in all tissues of metazoans. The discovery of these
      kinases is reviewed, followed by a discussion of some of the features of this
      signaling module that account for its broad impact on cell function and its
      enormous interest to many investigators.

PMID- 17229483
TI  - [Are SPA therapy and pulsed electromagnetic field therapy effective for chronic
      neck pain? Randomised clinical trial First part: clinical evaluation].
AB  - OBJECTIVES: The purpose of this study was to compare SPA therapy (ST) with pulsed
      electromagnetic field (PEMF) therapy in chronic neck pain. MATERIALS AND METHODS:
      Inclusion criteria were age between 18 and 80 years, neck pain of more than 3
      months' duration and pain score>30 mm on a visual analog scale (VAS). Exclusion
      criteria were contraindication to ST or PEMF. The protocol was approved by the
      ethics committee of Grenoble Hospital. Randomisation to the ST (n=44) and PEMF
      groups (n=42) was blinded. The main outcome measure was number of improved
      patients at 6 months in each group. A patient was considered improved if pain
      score decreased by more than 20%. Secondary measures were score on the Copenhagen
      and MOS SF-36 scales. Evaluation and intent-to-treat analysis were also blinded.
      RESULTS: Patients' preferences were for PEMF. At 6 months, in the PEMF group, 33
      patients were improved, 5 not improved and 4 lost to follow-up. In the ST group,
      24 patients were improved, 14 not improved and 6 lost to follow-up, for
      significantly greater improvement in the PEMF than ST group (p=0.02). Significant
      improvement was seen in both groups in terms of pain score, Copenhagen scale
      score and score on some dimensions of the MOS SF-36 survey. CONCLUSION: PEMF
      seems to be superior to standard ST without massage in control of neck pain. The
      difference between groups, although perhaps biased, seem to suggest the
      importance of our conclusions.

PMID- 17229485
TI  - Progress in QSAR toxicity screening of pharmaceutical impurities and other FDA
      regulated products.
AB  - Active ingredients in pharmaceutical products undergo extensive testing to ensure
      their safety before being made available to the American public. A consideration
      during the regulatory review process is the safety of pharmaceutical contaminants
      and degradents which may be present in the drug product at low levels. Several
      published guidances are available that outline the criteria for further testing
      of these impurities to assess their toxic potential, where further testing is in
      the form of a battery of toxicology assays and the identification of known
      structural alerts. However, recent advances in the development of computational
      methods have made available additional resources for safety assessment such as
      structure similarity searching and quantitative structure-activity relationship
      (QSAR) models. These methods offer a rapid and cost-effective first-pass
      screening capability to assess toxicity when conventional toxicology data are
      limited or lacking, with the potential to identify compounds that would be
      appropriate for further testing. This article discusses some of the
      considerations when using computational toxicology methods for regulatory
      decision support and gives examples of how the technology is currently being
      applied at the US Food and Drug Administration.

PMID- 17229484
TI  - High prevalence of glucose intolerance even among young adults in south India.
AB  - India is experiencing an epidemic of Type 2 diabetes mellitus (DM) in young
      adults. This study reports the prevalence of glucose intolerance, and insulin
      profiles, and their relationship to lifestyle factors in 2218 young adults (aged
      26-32 years; 997 urban, 1221 rural) in south India. They were drawn from a cohort
      of 10,691 individuals born during 1969-1973 in Vellore and nearby villages.
      Family history, socio-economic status, physical activity and tobacco and alcohol
      use were recorded. Oral glucose tolerance tests were performed for diagnosis (WHO
      recommendations). Insulin resistance and secretion were derived from plasma
      insulin concentrations. Median BMI was 20.0kg/m(2). The prevalence of Type 2 DM
      and impaired glucose tolerance (IGT) was higher in urban than in rural subjects
      (3.7% versus 2.1%, p=0.02; 18.9% versus 14.3%, p=0.002, respectively), while
      prevalence of impaired fasting glycaemia (IFG) was similar in urban and rural
      populations (3.8% versus 3.4%, p=0.04). Type 2 DM, IGT, IFG or higher insulin
      resistance and increment were associated with higher socio-economic status (more
      household possessions) and higher percentage body fat, body mass index and
      waist/hip ratio. Insulin increment was lower in men with higher alcohol
      consumption. Our data suggest high levels of glucose intolerance in young rural
      and urban adults highlighting an urgent need for preventive action to avert a
      public health catastrophe in India.

PMID- 17229486
TI  - Virtual bronchoscopic navigation system shortens the examination time-
      feasibility study of virtual bronchoscopic navigation system.
AB  - Computed tomography (CT)-guided transbronchial biopsy (TBB) using an ultrathin
      bronchoscope with simulation by virtual bronchoscopy (VB) is effective for
      diagnosing small peripheral pulmonary lesions. However, we occasionally lose the
      proper bronchi to the lesion when a bronchoscope is inserted into peripheral
      bronchi with severe rotation. To overcome this problem, the virtual bronchoscopic
      navigation system that can display real-time VB images during TBB procedures in
      comparison with actual bronchi has been developed. We evaluated the usefulness of
      the virtual bronchoscopic navigation system for CT-guided TBB using an ultrathin
      bronchoscope (navigation method) to diagnose small peripheral pulmonary lesions,
      and compared the results to those with previous method that uses VB images in a
      simulation (simulation method). We performed CT-guided TBB using an ultrathin
      bronchoscope for 69 patients with 71 small peripheral pulmonary lesions (mean
      diameter, 13.7 mm) between November 2002 and November 2005 with the navigation
      method. CT-guided TBB with the navigation method was performed safely without any
      serious complications for all patients. Mean time to the initial scan, time to
      the first biopsy and total examination time were 5.3, 8.5 and 24.5 min,
      respectively. Fifty lesions (70%) were diagnosed by this procedure. Compared to
      simulation method, diagnostic sensitivity was higher in the navigation method,
      but the difference was not significant. However, the time to the first biopsy and
      total examination time were significantly shorter in the navigation method than
      in the simulation method (p<0.05). In summary, the virtual bronchoscopic
      navigation system was safely used, effective for diagnosing small peripheral
      pulmonary lesions, and useful for shortening the examination time of CT-guided
      TBB using an ultrathin bronchoscope.

PMID- 17229487
TI  - Surgical management of lung cancer invading the aorta or the superior vena cava.
AB  - OBJECTIVE: Invasion of mediastinal structures (T4) is considered as an absolute
      contraindication to surgical management of non-small cell lung cancer (NSCLC).
      The authors studied the role of surgical treatment in case of direct aortic and
      superior venous caval involvement. PATIENTS: From 1995 to 2000, 13 patients with
      left lung NSCLC invading descending aorta and 9 patients with right upper lobe
      NSCLC and superior vena cava (SVC) invasion were subjected to thoracotomy for
      lung resection. Surgery was indicated in case of absence of intraluminal
      extension. All patients were cN2 negative. The pathology results and 5-year
      survival were recorded and analyzed. RESULTS: In three cases (23%) the tumor was
      adhered to the parietal pleura overlying descending aorta, which was resected en
      block with tumor-associated lung parenchyma. Aortic adventitia invasion by tumor
      led to local resection of adventitia (<1cm(2)) in nine patients (69%). Invasion
      deeper than adventitia was encountered in one case (8%), which was managed with
      aortic partial occlusion, resection of aortic wall and repair of the defect with
      Gore graft patch. In three patients (33%) the SVC wall was involved by the tumor
      1-3cm in length and 2-4mm of the circumference. The defect was repaired with
      direct suturing. In five patients (56%) the area of SVC wall that was invaded was
      3cmx2cm. The defect was repaired with Dacron patch. In 1 patient (11%) an
      arterial 14 graft was end-to-end interposed. All resections were radical (R0).
      Neither associated postoperative complications nor operative mortality was
      recorded. Five-year survival was 30.7% for the cases with aortic invasion and 11%
      for the ones with SVC involvement. CONCLUSIONS: Radical surgical resection of
      lung tumors with localized aortic invasion can be considered after exclusion of
      N2 involvement.

PMID- 17229488
TI  - A reaction-based paradigm to model reactive chemical transport in groundwater
      with general kinetic and equilibrium reactions.
AB  - This paper presents a reaction-based water quality transport model in subsurface
      flow systems. Transport of chemical species with a variety of chemical and
      physical processes is mathematically described by M partial differential
      equations (PDEs). Decomposition via Gauss-Jordan column reduction of the reaction
      network transforms M species reactive transport equations into two sets of
      equations: a set of thermodynamic equilibrium equations representing N(E)
      equilibrium reactions and a set of reactive transport equations of M-N(E) kinetic
      variables involving no equilibrium reactions (a kinetic-variable is a linear
      combination of species). The elimination of equilibrium reactions from reactive
      transport equations allows robust and efficient numerical integration. The model
      solves the PDEs of kinetic-variables rather than individual chemical species,
      which reduces the number of reactive transport equations and simplifies the
      reaction terms in the equations. A variety of numerical methods are investigated
      for solving the coupled transport and reaction equations. Simulation comparisons
      with exact solutions were performed to verify numerical accuracy and assess the
      effectiveness of various numerical strategies to deal with different application
      circumstances. Two validation examples involving simulations of uranium transport
      in soil columns are presented to evaluate the ability of the model to simulate
      reactive transport with complex reaction networks involving both kinetic and
      equilibrium reactions.

PMID- 17229489
TI  - Neuropeptide Y (NPY) in neuroblastoma: effect on growth and vascularization.
AB  - Neuroblastomas are pediatric tumors of sympathetic origin, expressing neuronal
      markers, such as NPY and its receptors. Due to this, neuroblastomas are often
      associated with elevated plasma levels of NPY, which correlates with poor
      clinical outcome of the disease. This clinical data corroborates the recent
      discovery of growth-promoting actions of NPY in neuroblastomas. The peptide has
      been shown to stimulate proliferation of neuroblastoma cells in an autocrine
      manner and induce tumor vascularization. Since both processes are mediated by the
      same Y2 and Y5 receptors, targeting this pathway may be a potential bidirectional
      therapy for these children's tumors.

PMID- 17229490
TI  - Existence of high and low affinity dinucleotides pentaphosphate-induced calcium
      responses in individual synaptic terminals and lack of correlation with the
      distribution of P2X1-7 subunits.
AB  - Individual analysis of synaptic terminals calcium responses, induced by
      dinucleotides pentaphosphate, Ap(5)A or Gp(5)G, demonstrates the presence of two
      main groups considering the concentration required for stimulation. The first
      group corresponds to those responding to Ap(5)A or Gp(5)G at nanomolar
      concentration, representing 16% and 12%, respectively, and the second one
      responds to micromolar concentration and represents, respectively, 17% and 14%,
      of the total functional synaptosomal population in rat midbrain. Dose-response
      curves in single terminals showed an Ap(5)A EC(50) values of 0.9+/-0.2 nM and
      11.8+/-0.9 microM, being the maximal intrasynaptosomal calcium increase of 200+/
      0.3 and 125+/-0.2 nM for the high and low affinity responding terminals,
      respectively. Combination of microfluorimetric and immunocytochemical studies
      showed lack of correlation between dinucleotides pentaphosphate responses and P2X
      receptor subunits expression, in spite of the abundance of P2X(2), P2X(3) and
      P2X(7) at the presynaptic level in rat midbrain synaptosomes. Pyridoxalphosphate
      6-azophenyl-2',4'-disulfonic acid (PPADS), a P2X receptors antagonist, showed no
      effect on low affinity dinucleotides receptors population, and partial inhibition
      on the high affinity one. On the other hand, diinosine pentaphosphate (Ip(5)I)
      completely abolished the low affinity dinucleotides responses, and 60% inhibition
      of the high affinity ones.

PMID- 17229491
TI  - [Videocapsule endoscopy as a useful tool to diagnose primary intestinal
      lymphangiectasia].
AB  - INTRODUCTION: Primary intestinal lymphangiectasia (Waldmann's disease) lead to a
      protein-losing enteropathy due to lymph leak into intestinal tract. EXEGESIS: A
      28-year-old woman presented a bilateral lower limb lymphedema. Laboratory
      examination showing lymphopenia, hypoalbuminemia, hypogammaglobulinemia suggested
      the diagnosis of primary intestinal lymphangiectasia. Gastroscopy was normal and
      second duodenum biopsies were negative. Videocapsule endoscopy gave evidence of
      intestinal lymphangiectasia of the small bowel. CONCLUSION: Videocapsule
      endoscopy may be proposed to confirm intestinal lymphangiectasia and to precise
      their localization when gastroscopy is not conclusive.

PMID- 17229492
TI  - [Haematological complications of prostatic cancer: 2 cases, one revealing the
      neoplasia].
AB  - INTRODUCTION: We report two cases of patients with prostate cancer who underwent
      haematological complications from the disease. CLINICAL CASES: Diffuse
      intravascular coagulopathy (with thrombopenia) was observed in two patients (55
      and 59 years-old) diagnosed with prostate cancer. In one patient who had normal
      prostate at clinical examination, thrombopenia with incomplete diffuse
      intravascular coagulopathy and biological inflammatory led to diagnosis. It was
      initially controlled by hormonal therapy and secondary by chemotherapy. In the
      other patient diffuse intravascular coagulopathy followed introduction of
      hormonal therapy and lead to the patient's death. DISCUSSION: Patients with
      metastatic hormone-refractory prostate carcinoma may have life-threatening
      coagulation complications due to their disease. Diffuse intravascular
      coagulopathy is the most frequent coagulation complication. Other coagulopathies
      associated with prostate cancer are thrombocytopenic thrombotic purpura,
      thrombosis, Trousseau's syndrome and acquired factor VIII inhibitor development.
      Usually these haematological manifestations complicate the course of the disease
      and appear to have a bad prognosis. But thrombopenia or haematologic features may
      lead to the diagnosis of medullary metastatic prostatic cancer, even if the
      prostate appears normal at the initial clinical examination.

PMID- 17229493
TI  - A dynamic model for assessing universal Hepatitis A vaccination in Canada.
AB  - Vaccination against Hepatitis A virus (HAV) in Canada is currently targeted
      toward high-risk groups. However, universal vaccination has been adopted in
      several other countries with a similar disease burden. Here we develop an age
      structured compartmental model of HAV transmission and vaccination in Canada to
      assess potential universal vaccination strategies. The model predicts that
      universal vaccination at age 1 (respectively 4, 9, 15), with phasing out of
      targeted vaccination, would reduce reported incidence by 60% (respectively 52,
      36, 31%) and mortality attributable to HAV by 56% (respectively 45, 26, 25%),
      relative to continued targeted vaccination, over 80 years.

PMID- 17229494
TI  - Immunogenicity and characterization of WRSF2G11: a second generation live
      attenuated Shigella flexneri 2a vaccine strain.
AB  - Recent clinical trials involving live attenuated Shigella vaccine strains SC602
      and WRSS1 have revealed that deletion of the virG(icsA) gene dramatically reduces
      virulence in human volunteers. These strains can be given at low oral doses and
      induce a strong, and in some cases, protective immune responses. However,
      residual vaccine associated reactogenicity suggests that further attenuation is
      required. A recent clinical trial indicated that the set and sen enterotoxin
      genes contribute to the symptoms of fever and diarrhea observed with live
      Shigella vaccine strains. Based on these findings, a Shigella flexneri 2a vaccine
      candidate, WRSf2G11, with deletions in the virG(icsA), set and sen genes has been
      constructed using the lambda red recombinase system. The immunogenicity and
      protective efficacy of WRSf2G11 compares favorably with SC602 following either
      intranasal (IN) or ocular (OC) immunization of guinea pigs. Taken together, these
      data indicate that second generation virG-based Shigella vaccine strains which
      lack enterotoxin genes, such as WRSf2G11, will likely show lower levels of
      reactogenicity without hampering the robust immune responses achieved with
      previous live vaccines.

PMID- 17229495
TI  - Analysis of anti-protective antigen IgG subclass distribution in recipients of
      anthrax vaccine adsorbed (AVA) and patients with cutaneous and inhalation
      anthrax.
AB  - The anti-PA IgG1, IgG2, IgG3, and IgG4 subclass responses to clinical anthrax and
      to different numbers of anthrax vaccine adsorbed (AVA, BioThrax) injections were
      determined in a cross-sectional study of sera from 63 vaccinees and 13 clinical
      anthrax patients. The data show that both vaccination with three AVA injections
      and clinical anthrax elicit anti-PA IgG1, IgG2, and IgG3 subclass responses. An
      anti-PA IgG4 response was detected in AVA recipients after the fourth injection.
      The anthrax lethal toxin (LTx) neutralization efficacy of sera from recipients
      who received 4 to > or =10 AVA injections did not vary significantly in relation
      to changes in distribution of anti-PA IgG1 and IgG4 subclasses.

PMID- 17229496
TI  - Diagnostic methods for detection of Classical swine fever virus--status quo and
      new developments.
AB  - Classical swine fever (CSF) is a highly contagious disease causing major losses
      in pig populations almost worldwide. The disease occurs in many regions of Asia,
      Central and South America and parts of Europe and Africa. Some countries have
      eradicated the disease (Australia, USA, Canada, within the EU), yet it keeps
      recurring sporadically (South Africa, Germany, Netherlands, England). The
      causative virus is a member of the genus Pestivirus, family Flaviviridae. The
      first diagnosis of CSF is based on the recognition of clinical signs by the
      veterinarian in the field and by post mortem findings. Many signs are not
      exclusively associated with CSF and they may vary with the strain of virus, age
      and health status of the pigs. Since clinical signs may be confused with other
      pig diseases, laboratory diagnosis of CSF is indispensable. Both the Office
      International des Epizooties (OIE) and the European Union, have approved
      diagnostic manuals establishing sampling methods and diagnostic procedures for
      the confirmation of the disease. In this review, experiences with current tests
      will be analyzed and complemented with new developments, with emphasis on the
      polymerase chain reaction after reverse transcription of the RNA genome (RT-PCR).

PMID- 17229497
TI  - Vaccination with porcine reproductive and respiratory syndrome killed virus
      vaccine and immunostimulatory oligodeoxynucleotides induces specific immunity in
      piglets.
AB  - A large number of studies demonstrated the immunostimulatory effects of CpG
      oligonucleotides (ODN), particularly in mice. In present study, the objective was
      to investigate the immunoadjuvant effects of CpG ODN to porcine reproductive and
      respiratory syndrome (PRRS) killed virus vaccine (PRRSV) and its protective
      effects against PRRS virus in piglets. The PRRSV-specific antibodies titres and
      serum IgG1/IgG2 titres, the proliferation of lymphocytes, PRRSV-specific IFN
      gamma, the expression of major histocompatibility complex class II (MHCII) of
      peripheral blood mononuclear cells (PBMCs) and post-challenge clinical protection
      were examined to identify the immune responses of the piglets. The results were
      found that the above-mentioned immune responses of the piglets inoculated with
      CpG ODN plus PRRSV were significantly stronger than those indued by PRRSV or PBS
      control groups. All these data suggested that CpG ODN could be employed as
      effective immunoadjuvant to raise the humoral and cellular responses of the
      piglets to PRRSV.

PMID- 17229498
TI  - Determinants of childhood vaccination coverage in Kazakhstan in a period of
      societal change: implications for vaccination policies.
AB  - After the fall of the Soviet Union countries in Central Asia have undergone large
      changes. In Kazakhstan the vaccination coverage decreased between 1990 and 1995,
      which resulted in an increased incidence of some vaccine-preventable diseases,
      e.g. diphtheria and measles. In this study we examined which factors affected the
      vaccination status of children in Kazakhstan and whether they resemble patterns
      observed in developing or developed countries. We found a mixed pattern of risk
      factors, consistent with the status of Kazakhstan as a transitional economy.
      Especially prominent was the relatively high education of the women and good
      access to the medical care system.

PMID- 17229499
TI  - Tumour immunity and T cell memory are induced by low dose inoculation with a non
      replicating adenovirus encoding TAP1.
AB  - Despite continued progress in understanding the pathophysiology of tumours,
      curative therapeutic options are still lacking for the metastatic form of the
      disease. One approach that has gathered considerable interest is the creation of
      therapeutic vaccines using genetically engineered non-replicating viruses as
      vehicles to revive immunosurveillance mechanisms that may eradicate residual
      tumour cells. A perceived problem with this approach is that the number of non
      replicating viruses used as a vaccine inoculum does not remotely approximate the
      total number of cells in the body, nor even the number of tumour cells in the
      case of large tumour burden or metastasis. Here, we addressed the hypothesis that
      a limited amount of inoculum (1x10(8) PFU) of recombinant non-replicating
      adenovirus encoding human TAP1 (AdhTAP1) can induce protective immunity against
      1.5x10(5) TAP-deficient, metastatic melanoma cells transplanted into a normal
      mouse (total of approximately 1x10(11) body cells). We show that efficacious anti
      tumour cytolytic T cell responses are indeed induced by injecting melanoma
      bearing animals with small numbers of recombinant viruses, resulting in increases
      in tumour-infiltrating dendritic cells, enhanced memory T cell subpopulations
      and, most importantly, in increased animal survival. This novel approach uses a
      limited input inoculum relative to the tumour cell mass, and thus achieves an
      efficacious outcome that has so far eluded other vaccine, immunotherapeutic or
      gene therapeutic strategies where there is a requisite for the majority of tumour
      cells to be transduced for beneficial outcome to be achieved.

PMID- 17229500
TI  - Development of a vaccine-challenge model for avian metapneumovirus subtype C in
      turkeys.
AB  - The objective of this study was to evaluate different preparations of avian
      metapneumovirus (aMPV) subtype C as vaccine challenge in turkeys. Two aMPV
      isolates and their respective nasal turbinate homogenates after propagation in
      turkeys were used in the study. Significantly higher clinical sign scores were
      recorded in birds inoculated with 20 or 2% turbinate homogenate of recent
      isolate. Birds in the above groups showed more pronounced histopathological
      lesions, and a higher percentage of birds showed viral RNA and antigen in
      tissues. The data demonstrated that nasal turbinate homogenate of recent isolate
      produced severe clinical signs and lesions in turkeys and could be an ideal
      candidate for vaccine-challenge studies.

PMID- 17229501
TI  - Intramuscular rather than oral administration of replication-defective adenoviral
      vaccine vector induces specific CD8+ T cell responses in the gut.
AB  - Gut-associated lymphoid tissue (GALT) is the primary replication site for HIV-1,
      resulting in a pronounced CD4(+) T cell loss in this tissue during primary
      infection. A mucosal vaccine that generates HIV-specific CD8(+) T cells in the
      gut could prevent the establishment of founder populations and broadcasting of
      virus. Here, we immunized mice orally and systemically with a chimpanzee derived
      adenoviral vector expressing HIV gag (AdC68gag) and measured frequencies of gag
      specific interferon-gamma (IFN-gamma) producing CD8(+) T cells in the GALT. A
      single oral administration was inefficient at eliciting responses in the
      mesenteric lymph nodes and Peyer's Patches, while a single intramuscular
      administration elicited strong systemic and detectable mucosal responses. The gag
      specific CD8(+) T cell responses were present in both acute and memory phases
      following intramuscular administration.

PMID- 17229502
TI  - Pertussis in Argentina and France.
AB  - We have studied the epidemiology of pertussis in two countries, Argentina and
      France, which have similar histories of long-term mass vaccination with a whole
      cell vaccine. Both countries display a comparable epidemiology, with an increase
      of the incidence of the disease in non-vaccinated newborns. We used pulsed-field
      gel electrophoresis (PFGE) analysis and genotyping to compare Bordetella
      pertussis clinical isolates recovered in Argentina and France in 2001-2004. The
      majority of the isolates harbors prn2 allele and belongs to PFGE IVbeta group.
      Isolates were found to be very similar genetically suggesting a common evolution
      of the disease in these two countries using the same vaccine.

PMID- 17229503
TI  - Enhanced protection against Streptococcus pyogenes infection by intranasal
      vaccination with a dual antigen component M protein/SfbI lipid core peptide
      vaccine formulation.
AB  - We investigated the efficacy of a synthetic Streptococcus pyogenes vaccine
      targeting two virulence factors using the Lipid Core Peptide (LCP) delivery
      system. BALB/c mice were immunised intranasally with LCPs containing peptides
      encompassing T-cell and B-cell epitopes of the conserved C-repeat region of the M
      protein (J8) or the fibronectin-binding repeats region (FNBR) of SfbI, or a
      combination formulation containing peptides representing both antigens. LCPs were
      co-administered with the TLR2/6 agonist MALP-2 as mucosal adjuvant. Humoral and
      cellular immune responses stimulated at systemic and mucosal levels were
      strongest in mice immunised with the dual antigen formulation. Mice were
      completely protected following a respiratory challenge with a lethal dose of a
      heterologous S. pyogenes strain, whereas there was 70% and 90% survival in mice
      immunised with LCP-J8 and LCP-FNBR, respectively. This is the first report
      demonstrating the elicitation of better protective immunity by a dual antigen
      component S. pyogenes vaccine.

PMID- 17229504
TI  - Babesia gibsoni ribosomal phosphoprotein P0 induces cross-protective immunity
      against B. microti infection in mice.
AB  - Babesia gibsoni ribosomal phosphoprotein P0 (BgP0) was identified as an
      immunodominant cross-reactive antigen with B. microti. The BgP0 gene is a single
      copy with a predicted open reading frame of 942 bp and 314 amino acids. The BgP0
      was expressed as a glutathione S-transferase fusion protein in Escherichia coli.
      The serum raised in mice with the recombinant BgP0 showed a specific band with a
      34-kDa molecular mass in the extracts of B. gibsoni and B. microti merozoites.
      Furthermore, the intraperitoneal (i.p.) immunization of rBgP0 and Freund's
      adjuvant induced strong humoral response consisting of mixed immunoglobulins IgG1
      and IgG2a in BALB/c mice. Following the challenge with B. microti, these mice
      delayed the onset of parasites and significantly reduced the peripheral
      parasitemia. On the other hand, passive-transfer of purified anti-BgP0 IgG into
      SCID mice showed partial protection against B. microti challenge infection. It
      was only effective in restricting the initial parasitemia but not later during
      its progress. Taken together, the immunological response elicited by rBgP0
      protected the mice against B. microti challenge infection. These data suggest
      that BgP0 is a potentially universal vaccine candidate for both B. gibsoni and B.
      microti infections.

PMID- 17229506
TI  - Re: Conservative, non-surgical management of patients presenting with impacted
      lower third molars: a 5-year study. Br J Oral Maxillofac Surg 2006;44:347-50.

PMID- 17229507
TI  - A qualitative study of the experiences of Taiwanese women having their first baby
      after the age of 35 years.
AB  - OBJECTIVE: to explore the experiences of Taiwanese women who become pregnant for
      the first time after the age of 35 years. DESIGN, SETTING AND PARTICIPANTS: a
      phenomenological method was used to collect data by interviews. This study was
      undertaken in a 1600-bed university hospital in southern Taiwan, with a purposive
      sampling of 10 first-time pregnant women aged 35-44 years. The interviews were
      tape-recorded and transcribed to develop data categories. FINDINGS: participants
      amply demonstrated that the core experience was 'jubilant apprehension' (Yu-Shee
      Zhun-Ben in Mandarin). Five subcategories were expressed among pregnant women
      over 35 years of age. These were 'surprise and worry about childbirth outcomes;'
      'embarrassment about being outside the societal age norm for pregnancy;'
      'ambivalence about impending lifestyle changes;' 'loneliness and lack of
      support;' and 'concern about the safety of pregnancy and childbirth'. CONCLUSION
      AND IMPLICATIONS FOR PRACTICE: although pregnancy was a pleasant surprise for
      these women, they were concerned that their childbearing was beyond the social
      expectation for their age. We highlight new aspects of midwifery professionalism
      that should address the childbearing experience of women over 35 years of age,
      and provide a basis for care of this group.

PMID- 17229508
TI  - Developing psychological perspectives of suicidal behaviour and risk in people
      with a diagnosis of schizophrenia: we know they kill themselves but do we
      understand why?
AB  - People with a diagnosis of schizophrenia are at increased risk of suicidal
      behaviour yet little is understood of the psychological underpinnings of this
      vulnerability. The biopsychosocial 'Cry of Pain' model [Williams, J.M.G. (1997).
      Cry of pain. Harmondsworth: Penguin.] provides a broad framework from which to
      understand suicidal behaviour. However, the utility of the model in relation to
      suicide in schizophrenia has not yet been explored. This was the primary goal of
      this paper. Six components of the 'Cry of Pain' model were identified and
      evaluated with respect to whether they contributed to i. common transdiagnostic
      factors underlying suicide, ii. factors relating to co-morbid depression which
      account for suicidal behaviour, or iii. factors which are specific to
      schizophrenia and underlie suicide risk. The potential for applying the model to
      clinical management of suicide in schizophrenia is illustrated.

PMID- 17229505
TI  - Adjuvant-enhanced antibody responses to recombinant proteins correlates with
      protection of mice and monkeys to orthopoxvirus challenges.
AB  - Recombinant proteins are being evaluated as smallpox and monkeypox vaccines
      because of their perceived safety compared to live vaccinia virus. Previously, we
      demonstrated that three or more injections of a Ribi-type adjuvant with a
      combination of three proteins from the outer membranes of intracellular (L1
      protein) and extracellular (A33 and B5 proteins) forms of vaccinia virus
      protected mice against a lethal intranasal challenge with vaccinia virus. Here,
      we compared several adjuvants and found that QS-21 and to a lesser extent
      alum+CpG oligodeoxynucleotides accelerated and enhanced neutralizing antibody
      responses to a mixture of L1 and A33 proteins, provided the highest ratio of
      IgG2a to IgG1 isotype response, and protected mice against disease and death
      after only two immunizations 3 weeks apart. In addition, monkeys immunized with
      recombinant vaccinia virus proteins and QS-21 developed neutralizing antibody to
      monkeypox virus and had reduced virus load, skin lesions, and morbidity compared
      to the non-immunized group following monkeypox virus challenge.

PMID- 17229509
TI  - An arginine vasopressin V1b antagonist, SSR149415 elicits antidepressant-like
      effects in an olfactory bulbectomy model.
AB  - Olfactory bulbectomized (OB) rats have been considered to serve as a useful
      animal model of depression in terms of behavioral, neurochemical, and
      neuroendocrine alterations, which reflect symptoms of patients with major
      depression. These behavioral and neurochemical changes in OB rats are normalized
      by the chronic administration of antidepressants. Recently, it has been reported
      that the compounds acting on stress-related peptide receptors such as an arginine
      vasopressin 1b (V(1b)) receptor antagonist and corticotropin-releasing factor
      (CRF) 1 receptor antagonists have antidepressant-like effects in several animal
      models. Here, the effects of acute and chronic (14 days) treatment with a V(1b)
      receptor antagonist (SSR149415) and a CRF1 receptor antagonist (CP-154,526) were
      examined in olfactory bulbectomy-induced hyperemotionality. Oral acute treatment
      with SSR149415 or CP-154,526 did not affect olfactory bulbectomy-induced
      hyperemotionality. In contrast, oral chronic treatment with SSR149415 (10 and 30
      mg/kg) or CP-154,526 (10 mg/kg) significantly reduced hyperemotionality. The
      present results suggest that stress-related peptides such as arginine vasopressin
      and CRF might be implicated in olfactory bulbectomy-induced hyperemotionality.
      Furthermore, blockade of the V(1b) receptor or the CRF1 receptor may be useful in
      treating subjects suffering from chronic stressful conditions.

PMID- 17229510
TI  - Mental health outcomes following naltrexone implant treatment for heroin
      dependence.
AB  - BACKGROUND: Oral naltrexone is an approved treatment for opioid dependence.
      However, the impact of sustained release naltrexone on the mental health of
      treated opioid users has not been studied. AIMS: To assess if naltrexone via
      implant treatment was associated with any change in (i) risk, (ii) rate, and
      (iii) duration for hospital morbidity related to several categories of mental
      disorders among treated heroin users. METHOD: A cohort of 359 heroin users
      treated with sustained release naltrexone via implants in Western Australia was
      retrospectively followed up for mental health related outcomes via a health
      record linkage system over an average period of 1.78 years post-treatment.
      RESULTS: Individual patient's risk for hospital mental diagnoses was not altered
      after naltrexone implant. On a population cohort level, hospital admission rates
      related to all mental health problems, except mood disorders, declined
      significantly post-treatment; however, length of hospital stay did not improve.
      Overall, young, female patients or those with pre-existing mental illness were
      more likely than other patients to require hospital care for mental health issues
      following treatment. Longer period of heroin use was associated with poorer mood
      outcomes. CONCLUSIONS: Naltrexone implants were not associated with an increased
      risk for hospitalisation due to mental illness, and in most cases, were
      associated with a decrease in mental related hospital admission rate.

PMID- 17229512
TI  - Cilioretinal arterial occlusion phenomenon: a rare cause of loss of vision in
      pregnancy.

PMID- 17229511
TI  - Apoptotic and necrotic effects of hexanedione derivatives on the human
      neuroblastoma line SK-N-SH.
AB  - The potential cytotoxicity of two hexanedione food additives (2,3 and 3,4
      isomers) was evaluated in comparison with the neurotoxic hexane metabolite 2,5
      hexanedione in the human SK-N-SH neuroblastoma line using the MTT assay to
      indicate mitochondrial dehydrogenase activity and flow cytometry to monitor the
      cell cycle over 48 h. The IC(50)s of the 2,3-hexanedione (3.3+/-0.1 mM) and 3,4
      hexanedione (3.5+/-0.1 mM), indicated that the sensitivity of the cells was
      approximately seven-fold greater to these toxins compared with the 2,5 derivative
      (IC(50) of 22.4+/-0.2 mM). Comparison between the respective IC(50)s of the 2,3
      hexanedione and 3,4-hexanedione revealed no difference between the two isomers in
      terms of their effects on MTT turnover. With flow cytometry analysis, all three
      hexanediones showed increases in apoptosis within their respective concentration
      ranges of toxicity shown previously by MTT. In the presence of 2,5-hexanedione,
      between 8.5 and 17 mM concentrations, there was a significant increase in
      apoptotic nucleoids which was accompanied by a significant fall in the percentage
      of nucleoids in the G0/G1 phase (72.4+/-0.3-45.3+/-0.6%,), and a rise in the
      numbers of cells in the G2/M phase. This is likely to indicate growth arrest at
      cell cycle G2/M checkpoint in response to toxin damage. G2/M accumulation was
      also shown with 3,4 and 2,3 HD, which was maximal at much lower concentrations
      (approximately 4 and 3mM, respectively). Arrest at G1 and G2/M phase is
      indicative of inhibition of the cell cycle at the stages of DNA replication and
      chromosome segregation, respectively. It was also apparent that flow cytometry,
      rather than the MTT assay, did distinguish between the effects of the alpha
      diketones 2,3-hexanedione and 3,4-hexanedione on the cell cycle. At a
      concentration of 5.8mM 3,4-hexanedione, the percentage of apoptotic nucleoids was
      10.9+/-0.8% whilst apoptosis induced by 3,4-hexanedione had already reached a
      maximal level of 60.4+/-0.5%. In summary, flow cytometry indicated that the 3,4
      hexanedione derivative was more toxic than its 2,3 isomer and that both food
      additives caused interruption in the neuroblastoma cell cycle and further
      investigation may be required to assess if these alpha-diketones present in diets
      pose any possible risks to human health.

PMID- 17229513
TI  - The effect of withholding gonadotropin (a coasting period) on the outcome of in
      vitro fertilization cycles.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of coasting
      (withdrawing gonadotropin administration) on the cycle outcomes, including total
      number and quality of oocytes and embryos and pregnancy rate in patients
      undergoing in vitro fertilization. STUDY DESIGN: Sixty-seven patients undergoing
      coasting were evaluated in a retrospective study at the Royan Institute between
      May 2002 and June 2003. All patients underwent standard long protocol with
      gonadotropin-releasing hormone (GnRH) analogue and human menopausal gonadotropin
      (HMG) and then in vitro fertilization and embryo transfer (IVF-ET). Coasting was
      considered when the estradiol level was more than 3000 pg/ml and the number of
      follicles >10 in each ovary. HCG was administered whenever estradiol reached < or
      =3000 pg/ml and then the (IVF-ET) program was carried out. According to coasting
      periods, patients were divided into two groups: coasting period < or =3 days and
      coasting period >3 days. Statistical comparisons were performed using Student's t
      test and Fisher's exact test. RESULTS: There were no significant differences
      between the two groups with regard to mean age, body mass index (BMI), number of
      polycystic ovary syndrome (PCOS) patients, number of HMG ampoules and stimulation
      duration. The total number of retrieved oocytes decreased significantly in
      patients with more than 3 days of coasting (P=0.04). The number of high quality
      oocytes also decreased in this group; however, this did not reach significant
      levels. There were no significant differences between the two groups with regard
      to fertilization and pregnancy rate. None of the patients developed severe
      ovarian hyperstimulation syndrome (OHSS). CONCLUSION: This study reveals that a
      long coasting period (>3 days) has a negative effect on the number of oocytes,
      although the fertilization and pregnancy rates are not affected. Prospective
      randomized studies with larger sample sizes are needed to compare coasting with
      other procedures.

PMID- 17229514
TI  - Effect of alpha-crystallin on thermal denaturation and aggregation of rabbit
      muscle glyceraldehyde-3-phosphate dehydrogenase.
AB  - The study of thermal denaturation of rabbit muscle glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH) in the presence of alpha-crystallin by differential
      scanning calorimetry (DSC) showed that the position of the maximum on the DSC
      profile (T(max)) was shifted toward lower temperatures with increasing alpha
      crystallin concentration. The diminishing GAPDH stability in the presence of
      alpha-crystallin has been explained assuming that heating of GAPDH induces
      dissociation of the tetrameric form of the enzyme into dimers interacting with
      alpha-crystallin. The dissociation of the enzyme tetramer was shown by
      sedimentation velocity at 45 degrees C. Suppression of thermal aggregation of
      GAPDH by alpha-crystallin was studied by dynamic light scattering under the
      conditions wherein temperature was elevated at a constant rate. The construction
      of the light scattering intensity versus the hydrodynamic radius (R(h)) plots
      enabled estimating the hydrodynamic radius of the start aggregates (R(h,0)). When
      aggregation of GAPDH was studied in the presence of alpha-crystallin, the start
      aggregates of lesser size were observed.

PMID- 17229515
TI  - Development of a seeded scaffold in the great omentum: feasibility of an in vivo
      bioreactor for bladder tissue engineering.
AB  - OBJECTIVES: Tissue engineering is very promising in bladder reconstruction.
      However, one of the main problems is to limit the development of ischaemic
      fibrosis during tissue maturation. We describe a model using the omentum as an in
      vivo bioreactor for a previously seeded scaffold. METHODS: Bladder biopsies were
      taken from five female pigs, from which both urothelial and smooth muscle cells
      cultures were made. These cultured cells were used to seed a sphere-shaped small
      intestinal submucosa (SIS) matrix, which was transferred into the omentum after 3
      wk of cell growth. The grafts were harvested 3 wk later and histologic,
      immunohistochemical, and functional studies were performed. RESULTS: We obtained
      a highly vascularized tissue-engineered construct that contracted in response to
      acetylcholine stimulation. The wall thickness was 4mm, on average. Histologic and
      immunostaining analysis of the construct confirmed the presence of a multilayer
      urothelium on the luminal aspect and deeper fascicles organised tissue composed
      of differentiated smooth muscle cells and mature fibroblasts without evidence of
      inflammation or necrosis. Large- and small-diameter vessels were clearly
      identified histologically in the tissue obtained. CONCLUSION: The omentum
      permitted in vivo maturation of seeded scaffolds with the development of a dense
      vascularisation that is anticipated to prevent fibrosis and loss of
      contractility. This in vivo maturation into the omentum could be the first step
      before in situ implantation of the construct.

PMID- 17229516
TI  - Reply to M.V. Meng's Letter to the Editor re: H. Baumert et al. The use of
      polymer (Hem-o-lok) clips for management of the renal hilum during laparoscopic
      nephrectomy. Eur Urol 2006;49:816-9 and P.L. Steinberg et al. re: H. Baumert et
      al. The use of polymer (Hem-o-lok) clips for management of the renal hilum during
      laparoscopic nephrectomy. Eur Urol 2006;49:816-9. Eur Urol 2007;51:572-3.

PMID- 17229517
TI  - Cytoskeleton fragments unveiling bladder cancer.

PMID- 17229518
TI  - Docetaxel and beyond.

PMID- 17229519
TI  - Words of wisdom: re: survival associated with treatment vs observation of
      localized prostate cancer in elderly men. Wong Y, Mitra N, Hudes G, et al. JAMA
      2006;296:2683-93.

PMID- 17229520
TI  - Editorial comment on: The learning curve in the training of percutaneous
      nephrolithotomy.

PMID- 17229521
TI  - A review on follow-up strategies for renal cell carcinoma after nephrectomy.
AB  - OBJECTIVES: To provide a comprehensive review of the evidence supporting the
      necessity for follow-up after nephrectomy for renal cell carcinoma. METHODS: We
      searched the Medline, MeSH, EMBASE, and Cochrane databases using the terms "renal
      cell cancer," "kidney neoplasm," "follow-up," "surveillance," "prognosis," and
      "staging" to look for human/English language/Randomized Controlled
      Trials/Clinical trials/Review articles/Meta-analysis/Practiced Guidelines, and
      Editorials. RESULTS: No consensus currently exists on surveillance guidelines
      after radical or partial nephrectomy for renal cell carcinoma. The rationale for
      follow-up strategies is to detect local recurrence or metastatic disease and to
      allow appropriate treatment. Most of the surveillance protocols recommend various
      follow-up strategies for all tumour stages. The emphasis on follow-up should be
      during the first 3-5 yr after nephrectomy. There is no consensus about which
      investigations should be performed and at what intervals. Most surgeons rely on
      symptom enquiry, physical examination, chest x-ray, and computed tomography
      scanning. A protocol based on the stage of the initial tumour is adapted by the
      majority of the investigators. Patients should be followed similarly after
      radical or partial nephrectomy on the basis of stage-oriented protocols. The
      combination of various prognostic factors requires further validation over stage
      based protocols. There is a paucity of guidelines in the literature regarding
      follow-up for patients with hereditary forms of renal cell carcinoma.
      CONCLUSIONS: Current guidelines for follow-up are based on observational and case
      studies. While this fact precludes a high level of evidence-based guidelines, we
      have to conclude that this is the best available evidence to date.

PMID- 17229522
TI  - The learning curve in the training of percutaneous nephrolithotomy.
AB  - OBJECTIVES: To investigate the learning curve in the training of percutaneous
      nephrolithotomy (PCNL). METHODS: A total of 104 PCNL cases were included in this
      evaluation to define the learning curve of a surgeon with no previous experience
      at performing solo PCNL. Two parameters of expertise were reviewed, namely the
      operation and fluoroscopic screening times. The operation time was calculated as
      the beginning of access with the needle until the nephrostomy tube was placed and
      secured. PCNL procedures were analyzed in seven sets of 15 cases regarding the
      operation and fluoroscopy times, stone size, stone clearance rate, blood
      transfusion rate, and estimated blood loss. RESULTS: The mean operation time was
      2.4 h for the first 15 patients. It decreased to a mean of 1.5 h for cases 46
      through 60. No further decrease in the operation time was observed after case 60.
      The fluoroscopic screening time was a peak of 17.5 min in the first 15 cases,
      whereas it dropped to a mean of 8.9 min for cases 46 through 60. The decline in
      the mean fluoroscopy screening time continued in cases 61 to 104, but the decline
      was not significant. There was no significant difference in stone size, stone
      clearance rate, blood transfusion rate, and estimated blood loss among each set
      of cases. CONCLUSIONS: This study suggests that the surgical competence in PCNL
      can be reached after 60 cases. PCNL and fluoroscopy times drop to a steady-state
      level after performing 60 procedures.

PMID- 17229523
TI  - Pretreatment of wastewater from triazine manufacturing by coagulation,
      electrolysis, and internal microelectrolysis.
AB  - We studied the pretreatment of concentrated wastewater from triazine
      manufacturing by coagulation, electrolysis, and internal microelectrolysis.
      Results show that coagulation by polyaluminum chloride at dosage of 0.5 g/L could
      remove up to 17.2% chemical oxygen demand (COD) from the wastewater. Electrolysis
      using iron electrode achieved 33.2% COD removal at current of 2A in 180 min,
      which was attributed to coagulation and oxidation of the organic contaminants in
      the wastewater by the radicals (OH and O) and oxidants (O2, O3, and H2O2)
      produced in electrochemical reactions. Internal microelectrolysis using iron
      chips and granular activated carbon (GAC) showed that up to 60.5% COD could be
      removed under the conditions of iron/GAC/wastewater volumetric ratio of 3:2:490,
      sparge ratio (ratio of air flow rate to volume of wastewater) of 2:490 min(-1),
      and reaction time of 132 h. COD reduction in internal microelectrolysis was
      attributed to a combination of chemical and physical processes, mainly oxidation
      by radicals and oxidants formed in electrochemical reactions, adsorption on, co
      precipitation with, and enmeshment in ferrous and ferric hydroxides resulted from
      Fe2+ released during anode oxidation. The results suggest that internal
      microelectrolysis using iron chips and GAC is a promising, low-cost alternative
      for pretreating concentrated wastewater from pesticide manufacturing.

PMID- 17229524
TI  - BDNF tagging polymorphisms and haplotype analysis in sporadic Parkinson's disease
      in diverse ethnic groups.
AB  - Experimental and clinical data suggest that genetic variations in brain-derived
      neurotrophic factor (BDNF) gene may affect risk for Parkinson's disease (PD). We
      performed a case-control association analysis of BDNF in three independent
      Caucasian cohorts (Greek, North American, and Finnish) of PD using eight tagging
      SNPs and five constructed haplotypes. No statistically significant differences in
      genotype and allele frequencies were found between cases and controls in all
      series. A relatively rare BDNF haplotype showed a trend towards association in
      the Greek (p=0.02) and the Finnish (p=0.03) series (this haplotype was not
      detected in the North American series). However, given the large number of
      comparisons these associations are considered non-significant. In conclusion, our
      results do not provide statistically significant evidence that common genetic
      variability in BDNF would associate with the risk for PD in the Caucasian
      populations studied here.

PMID- 17229525
TI  - An exodeoxyribonuclease from Streptomyces coelicolor: expression, purification
      and biochemical characterization.
AB  - Streptomyces coelicolor A3(2) produces several intra and extracellular enzymes
      with deoxyribonuclease activities. The examined N-terminal amino acid sequence of
      one of extracellular DNAases (TVTSVNVNGLL) and database search on S. coelicolor
      genome showed a significant homology to the putative secreted
      exodeoxyribonuclease. The corresponding gene (exoSc) was amplified, cloned,
      expressed in Escherichia coli, purified to homogeneity and characterized.
      Exonuclease recExoSc degraded chromosomal, linear dsDNA with 3'-overhang ends,
      linear ssDNA and did not digest linear dsDNA with blunt ends, supercoiled plasmid
      ds nor ssDNA. The substrate specificity of recExoSc was in the order of
      dsDNA>ssDNA>3'-dAMP. The purified recExoSc was not a metalloprotein and exhibited
      neither phosphodiesterase nor RNase activity. It acted as 3'-phosphomonoesterase
      only at 3'-dAMP as a substrate. The optimal temperature for its activity was 57
      degrees C in Tris-HCl buffer at optimal pH=7.5 for either ssDNA or dsDNA
      substrates. It required a divalent cation (Mg(2+), Co(2+), Ca(2+)) and its
      activity was strongly inhibited in the presence of Zn(2+), Hg(2+), chelating
      agents or iodoacetate.

PMID- 17229526
TI  - Purification and kinetic properties of 6-phosphofructo-1-kinase from gilthead sea
      bream muscle.
AB  - The kinetic properties of 6-phosphofructo-1-kinase (PFK) from skeletal muscle
      (PFKM) of gilthead sea bream (Sparus aurata) were studied, after 10,900-fold
      purification to homogeneity. The native enzyme had an apparent molecular mass of
      662 kDa and is composed of 81 kDa subunits, suggesting a homooctameric structure.
      At physiological pH, S. aurata PFKM exhibited sigmoidal kinetics for the
      substrates, fructose-6-phosphate (fru-6-P) and ATP. Fructose-2,6-bisphosphate
      (fru-2,6-P(2)) converted the saturation curves for fru-6-P to hyperbolic,
      activated PFKM synergistically with other positive effectors of the enzyme such
      as AMP and ADP, and counteracted ATP and citrate inhibition. The fish enzyme
      showed differences regarding other animal PFKs: it is active as a homooctamer,
      and fru-2,6-P(2) and pH affected affinity for ATP. By monitoring incorporation of
      (32)P from ATP, we show that fish PFKM is a substrate for the cAMP-dependent
      protein kinase. The mechanism involved in PFKM activation by phosphorylation
      contrasts with previous observations in other species: it increased V(max) and
      did not affect affinity for fru-6-P. Unlike the mammalian muscle enzyme, our
      findings support that phosphorylation of PFKM may exert a major role during
      starvation in fish muscle.

PMID- 17229527
TI  - An accidental burn resulted from whole body hyperthermia therapy.

PMID- 17229528
TI  - Menthol cigarettes and indicators of tobacco dependence among adolescents.
AB  - OBJECTIVES: This study examines measures of nicotine dependence among adolescent
      menthol and non-menthol cigarette smokers in a nationally representative sample.
      METHODS: We examined rates of menthol smoking and measures of nicotine dependence
      among 1345 current established smokers in grades 9-12 who participated in the
      2004 National Youth Tobacco Survey. Logistic regression was used to generate an
      adjusted odds ratio (OR) for menthol smoking for four measures of nicotine
      dependence, controlling for demographic characteristics and smoking patterns.
      RESULTS: Approximately 46% of all current established cigarette smokers were
      menthol smokers. Menthol smokers had 2.6 and 1.6 greater odds than non-menthol
      smokers for reporting that they could go for less than 1 h before feeling like
      they need a cigarette and that they experience cravings after not smoking for a
      while, respectively. CONCLUSIONS: Menthol cigarette smoking was associated with
      two dependence measures and may be more addictive than regular cigarettes in
      young smokers. Future research should continue to explore relationships between
      dependency and menthol use as well as the high prevalence of menthol use among
      adolescents.

PMID- 17229529
TI  - Acute opiate overdose in Tehran: the forgotten role of opium.
AB  - INTRODUCTION: The global epidemic of opiate use continues to spread and is an
      increasing burden especially in developing countries. Acute opiate overdose (AOO)
      is one of the most dramatic complications of drug abuse. The purpose of this
      study is to examine the epidemiology of acute opiate overdose in a poisoning
      center in Tehran. METHODS: In this cross-sectional survey, patients who attended
      the emergency room of Loghman-Hakim hospital - the only poisoning center in
      Tehran - and diagnosed with acute opiate overdose over a six month period were
      included. RESULTS: Overdose was more common among men (91.2%). The mean and
      standard deviation of age was 36.9+/-15. The most frequent opiate agent was opium
      (56.5%) followed by heroin. Opium was most commonly used by regular users, as a
      single agent and through ingestion. Benzodiazepines, antidepressants and alcohol
      were the most common agents consumed accompanied with opiates. The mortality rate
      was 8.8% which was not significantly different between cases of heroin and opium
      overdose. CONCLUSION: Opium was the major cause of overdose in our study. This
      result suggests that opium is not a harmless form of addiction although it is
      regarded as a thing of the past in many countries.

PMID- 17229530
TI  - Conditioned taste avoidance induced by forced and voluntary wheel running in
      rats.
AB  - Voluntary exercise by rats running in a freely rotating wheel (free wheel)
      produces conditioned taste avoidance (CTA) of a flavored solution consumed before
      running [e.g., Lett, B.T., Grant, V.L., 1996. Wheel running induces conditioned
      taste aversion in rats trained while hungry and thirsty. Physiol. Behav. 59, 699
      702]. Forced exercise, swimming or running, also produces CTA in rats [e.g.,
      Masaki, T., Nakajima, S., 2006. Taste aversion induced by forced swimming,
      voluntary running, forced running, and lithium chloride injection treatments.
      Physiol. Behav. 88, 411-416]. Energy expenditure may be the critical factor in
      producing such CTA. If so, forced running in a motorized running wheel should
      produce CTA equivalent to that produced by a similar amount of voluntary running.
      In two experiments, we compared forced running in a motorized wheel with
      voluntary running in a free wheel. Mean distance run over 30 min was equated as
      closely as possible in the two apparatuses. Both types of exercise produced CTA
      relative to sedentary, locked-wheel controls. However, voluntary running produced
      greater CTA than forced running. We consider differences between running in the
      free and motorized wheels that may account for the differences in strength of
      CTA.

PMID- 17229531
TI  - A possible novel function of dominance behaviour in queen-less colonies of the
      primitively eusocial wasp Ropalidia marginata.
AB  - Unlike the queens of other primitively eusocial species, Ropalidia marginata
      queens are strikingly docile and non-aggressive individuals, never at the top of
      the behavioural dominance hierarchy of their colonies. Nevertheless, these queens
      are completely successful at suppressing worker reproduction, suggesting that
      they do not use aggression but employ some other mechanism (e.g. pheromones) to
      do so. Upon removal of the queen from a colony, a single worker, the 'potential
      queen', immediately begins to display highly elevated levels of aggression
      towards her nest mates. This individual becomes the next docile queen if the
      original queen is not returned. We attempt to understand the function of the
      temporary and amplified dominance behaviour displayed by the potential queen. We
      find that the dominance behaviour shown by the potential queen is unrelated to
      the number of her nest mates, their dominance ranks or ovarian condition. This
      suggests that aggression may not be used to actively suppress other workers and
      counter threat. Instead we find evidence that dominance behaviour is required for
      the potential queen's rapid ovarian development, facilitating her speedy
      establishment as the sole reproductive individual in the colony.

PMID- 17229532
TI  - Spirituality/religiosity promotes acceptance-based responding and 12-step
      involvement.
AB  - BACKGROUND: Previous investigations have observed that spirituality/religiosity
      (S/R) is associated with enhanced 12-step involvement. However, relatively few
      studies have attempted to examine the mechanisms for this effect. For the present
      investigation, we examined whether acceptance-based responding (ABR) - awareness
      or acknowledgement of internal experiences that allows one to consider and
      perform potentially adaptive responses - accounted for the effect of S/R on 12
      step self-help group involvement 2 years after a treatment episode. METHODS: Data
      were collected as part of a multi-site treatment outcome study with 3698
      substance-dependent male veterans recruited at baseline. Assessments were
      conducted at baseline, discharge, 1-year follow-up, and 2-year follow-up. We
      utilized structural equation modeling to examine the relationships among latent
      variables of S/R, ABR, and 12-step involvement over time. RESULTS: In the final
      model, S/R was not directly related to 12-step involvement at 2-year follow-up.
      However, S/R predicted enhanced ABR at 1-year follow-up after accounting for
      discharge levels of ABR. In turn, ABR at 1-year follow-up predicted increased 12
      step involvement at 2-year follow-up after accounting for discharge levels of 12
      step involvement. CONCLUSIONS: S/R promotes the use of post-treatment self
      regulation skills that, in turn, directly contribute to ongoing 12-step self-help
      group involvement.

PMID- 17229533
TI  - Expression profile analysis of microRNA (miRNA) in mouse central nervous system
      using a new miRNA detection system that examines hybridization signals at every
      step of washing.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs, with a length of 19 to 23
      nucleotides, which appear to be involved in the regulation of gene expression by
      inhibiting the translation of messenger RNA. Expression profile analysis of
      miRNAs is necessary to understand their complex role in the regulation of gene
      expression during the development and differentiation of cells and in various
      tissues. We describe here a detection system for miRNA expression profiles, using
      a new type of DNA chip and fluorescent labeled cellular RNAs, which allows real
      time detection of hybridization signals at every step of washing and results in
      highly reproducible miRNA expression profiles. Using the system, we investigated
      the expression profiles of miRNA in the mouse central nervous system (CNS),
      namely the spinal cord, medulla oblongata, pons, cerebellum, midbrain,
      diencephalons, and cerebral hemispheres. The results indicated that although the
      CNS subregions expressed similar miRNA genes, the expression levels of the miRNAs
      varied among the subregions, suggesting that the CNS subregions specialized for
      different functions possess different expression profiles of miRNAs.

PMID- 17229534
TI  - Presence of Shiga toxin-producing E. coli O157:H7 in a survey of wild
      artiodactyls.
AB  - This study was carried out to evaluate the role of wild artiodactyls as
      reservoirs of Escherichia coli O157:H7 for livestock and humans. Retroanal
      mucosal swabs samples from 206 red deer (Cervus elaphus), 20 roe deer (Capreolus
      capreolus), 6 fallow deer (Dama dama) and 11 mouflon (Ovis musimon), collected
      during the hunting season (autumn-winter) in South-western Spain, were screened.
      Samples were pre-enriched in modified buffered peptone water, concentrated by an
      immunomagnetic separation technique and cultured onto selective cefixime
      tellurite sorbitol MacConkey agar. Polymerase chain reaction (PCR) was used to
      detect the presence of genes coding O157 and H7 antigens and the virulence
      factors verocytotoxin, intimin and enterohaemolysin. Three E. coli O157:H7
      isolates were obtained from red deer (1.5%). Two of them showed inability to
      ferment sorbitol and lack of beta-d-glucuronidase (GUD) activity, however, the
      other strain investigated was an atypical sorbitol-fermenting E. coli O157:H7
      with GUD(+) activity. This is the first report pointing to red deer as a
      reservoir of E. coli O157:H7 in Spain.

PMID- 17229535
TI  - The effect of a bifidobacter supplemented bovine milk on intestinal permeability
      of preterm infants.
AB  - BACKGROUND: Preterm infants have increased intestinal permeability which can
      render them susceptible to infections from enterobacteriae. OBJECTIVES: The
      primary objective was to investigate whether probiotic administration to preterm
      infants decreases intestinal permeability. Secondary outcomes studied were:
      somatic growth, tolerance, rates of sepsis and necrotizing enterocolitis.
      METHODS: In a prospective randomized case-control study 41 stable preterm infants
      of 27 to 36 weeks gestation and 34 matched comparison infants consecutively
      admitted to the neonatal unit were studied. The study group received a preterm
      formula supplemented with Bifidobacter lactis (2 x 10(7) cfu/g of dry milk) while
      the control group received the same formula but without supplementation.
      Intestinal permeability was measured within two days of birth and then seven and
      thirty days later using the sugar absorption test. Additionally anthropometric
      parameters were recorded throughout the study as well as acceptance and tolerance
      of the formula. RESULTS: All infants tolerated the study formula well. Median
      counts of stool bifidobacteria and lactulose/mannitol ratios at baseline were
      comparable. After 7 days of supplementation median bifidobacteria counts were
      significantly higher in the study group than in the control group (p=0.0356) and
      they remained higher to the end of the study (p at day 30=0.075). The L/M ratio
      in the study group was significantly lower at day 30 of the study as compared to
      the control group (p=0.003). Head growth was significantly higher in the study
      group (p=0.001). CONCLUSIONS: The administration of a bifidobacter supplemented
      infant formula decreases intestinal permeability of preterm infants and leads to
      increased head growth.

PMID- 17229536
TI  - Influence of free chains on the swelling pressure of PEG-HEMA and dex-HEMA
      hydrogels.
AB  - Insight in the osmotic behavior of degrading hydrogels is of great importance in
      the design of biodegradable hydrogels for biomedical applications. This study
      compares the degradation behavior of PEG-HEMA (hydroxyethylmethacrylated
      polyethylene glycol) and dex-HEMA (hydroxyethylmethacrylated dextran) hydrogels.
      The degradation of PEG-HEMA gels takes several months to over a year, while that
      of dex-HEMA gels takes only days or weeks. The faster degradation kinetics of dex
      HEMA networks can be attributed to stabilization of the keto-enol form by
      hydroxyl groups. Upon degradation of PEG-HEMA and dex-HEMA hydrogels,
      respectively, free PEG and free dextran chains are produced. We investigated the
      effect of unattached PEG and dextran chains on the swelling pressure of the
      degrading gels. It is found that low molecular weight free chains significantly
      increase the swelling pressure. However, the contribution of higher molecular
      weight free chains (M(w)>10 kDa) is similar to that of the network chains.

PMID- 17229537
TI  - Do Swiftlets have an ear for echolocation? The functional morphology of
      Swiftlets' middle ears.
AB  - The Oilbird and many Swiftlet species are unique among birds for their ability to
      echolocate. Echolocaters may benefit from improved hearing sensitivity.
      Therefore, morphological adaptations to echolocation might be present in
      echolocating birds' middle ears. We studied the functional morphology of the
      tympano-ossicular chain of seven specimens of four echolocating Swiftlet species
      and one specimen each of five non-echolocating species. Three dimensional (3D)
      reconstructions were made from micro-Computer-Tomographic (muCT) scans. The
      reconstructions were used in functional morphological analyses and model
      calculations. A two dimensional (2D) rigid rod model with fixed rotational axes
      was developed to study footplate output-amplitudes and to describe how changes in
      the arrangement of the tympano-ossicular chain affect its function. A 3D finite
      element model was used to predict ossicular-chain movement and to investigate the
      justification of the 2D approach. No morphological adaptations towards
      echolocation were found in the middle-ear lever system or in the mass impedance
      of the middle ear. A wide range of middle-ear configurations result in maximum
      output-amplitudes and all investigated species are congruent with these predicted
      best configurations. Echolocation is unlikely to depend on adaptations in the
      middle ear tympano-ossicular chain.

PMID- 17229538
TI  - Hypotensive effect and toxicology of the extract from Coscinium fenestratum
      (Gaertn.) Colebr.
AB  - The water extract from Coscinium fenestratum (Gaertn.) Colebr. (CF extract) was
      tested for hypotensive and vasorelaxant effects. Acute and subchronic toxicity as
      well as motor activity of CF extract were also evaluated. The present study
      demonstrates that CF extract is effective in reducing blood pressure in
      anesthetized normotensive rats. This effect is shown to be dose-related and rapid
      in onset. The extract showed an endothelium-dependent and independent
      vasorelaxant activity in isolated aortic rings precontracted with phenylephrine
      (1 microM) and KCl (60 mM). The capacity of L-NAME (100 microM), an inhibitor of
      nitric oxide synthase, to reduce the vasorelaxant action of the extract indicates
      the involvement of nitric oxide. In the acute toxicity test, an oral dose of 5000
      mg/kg of the CF extract did not produce mortality or significant changes of the
      general behavior of animals and gross appearance of internal organs of rats.
      Similarly, in the subchronic toxicity test, an oral dose of 2500 mg/kg/day of the
      CF extract given to rats for 90 days did not cause any significant change of any
      of the parameters observed when compared with those of the control animals.
      Moreover, the CF extract did not produce any effect on the central nervous system
      when spontaneous motor activity in rats was assessed. However, because some
      average hematological and blood chemistry values were found to be statistically
      different, further studies, including chronic toxicity test, should be done to
      confirm the safety of this plant when it is used over a long period of time.

PMID- 17229539
TI  - CT-MR image data fusion for computer assisted navigated neurosurgery of temporal
      bone tumors.
AB  - PURPOSE: To demonstrate the value of multi detector computed tomography (MDCT)
      and magnetic resonance imaging (MRI) in the preoperative work up of temporal bone
      tumors and to present, especially, CT and MR image fusion for surgical planning
      and performance in computer assisted navigated neurosurgery of temporal bone
      tumors. MATERIALS AND METHODS: Fifteen patients with temporal bone tumors
      underwent MDCT and MRI. MDCT was performed in high-resolution bone window level
      setting in axial plane. The reconstructed MDCT slice thickness was 0.8 mm. MRI
      was performed in axial and coronal plane with T2-weighted fast spin-echo (FSE)
      sequences, un-enhanced and contrast-enhanced T1-weighted spin-echo (SE)
      sequences, and coronal T1-weighted SE sequences with fat suppression and with 3D
      T1-weighted gradient-echo (GE) contrast-enhanced sequences in axial plane. The 3D
      T1-weighted GE sequence had a slice thickness of 1mm. Image data sets of CT and
      3D T1-weighted GE sequences were merged utilizing a workstation to create CT-MR
      fusion images. MDCT and MR images were separately used to depict and characterize
      lesions. The fusion images were utilized for interventional planning and
      intraoperative image guidance. The intraoperative accuracy of the navigation unit
      was measured, defined as the deviation between the same landmark in the
      navigation image and the patient. RESULTS: Tumorous lesions of bone and soft
      tissue were well delineated and characterized by CT and MR images. The images
      played a crucial role in the differentiation of benign and malignant pathologies,
      which consisted of 13 benign and 2 malignant tumors. The CT-MR fusion images
      supported the surgeon in preoperative planning and improved surgical performance.
      The mean intraoperative accuracy of the navigation system was 1.25 mm.
      CONCLUSION: CT and MRI are essential in the preoperative work up of temporal bone
      tumors. CT-MR image data fusion presents an accurate tool for planning the
      correct surgical procedure and is a benefit for the operational results in
      computer assisted navigated neurosurgery of temporal bone tumors.

PMID- 17229540
TI  - Comparing diffusion-weighted and T2-weighted MR imaging for the quantification of
      infarct size in a neonatal rat hypoxic-ischemic model at 24h post-injury.
AB  - PURPOSE: In a neonatal rat model of hypoxic-ischemic (HI) brain injury, using T2
      weighted imaging (T2WI) and diffusion-weighted imaging (DWI), we aim to determine
      the best MRI method of lesion quantification that reflects infarct size.
      MATERIALS AND METHODS: Twenty 7-day-old rats underwent MRI 24h after HI brain
      injury was induced. Lesion size relative to whole brain was measured using T2WI
      and apparent diffusion coefficient (ADC) maps, applying thresholds of 60%, 70%
      and 80% contralateral control hemisphere mean ADC, and at day 10 post-HI on
      pathology with TTC staining. Multiple linear regression analysis was used to
      study the relationships between lesion size at MRI and pathology. RESULTS: Lesion
      size measurement using all MRI methods significantly correlated with infarct size
      at pathology; using T2WI, r=0.808 (p<0.001), using 80% ADC, 70% ADC and 60% ADC
      thresholds, r=0.888 (p<0.001), 0.761, (p<0.001) and 0.569 (p=0.014),
      respectively. Eighty percent ADC threshold was found to be the only significant
      independent predictor of final infarct volume (adjusted R(2)=0.775). CONCLUSION:
      At 24h post-HI, lesion size on DWI, using 80% ADC threshold is the best predictor
      of final infarct volume. Although T2WI performed less well, it has the advantage
      of superior spatial resolution and is technically less demanding. These are
      important considerations for experiments which utilize MRI as a surrogate method
      for lesion quantification in the neonatal rat HI model.

PMID- 17229541
TI  - Changes in microtubule-associated protein-2 (MAP2) expression during development
      and after status epilepticus in the immature rat hippocampus.
AB  - In this study, we analyzed the spatiotemporal expression patterns of the high
      molecular weight (MAP2a and b) and low-molecular weight (MAP2c and d)
      cytoskeletal microtubule-associated protein-2 (MAP2) isoforms with Western
      blotting, and the cellular localization of the high-molecular weight MAP2
      isoforms with immunocytochemistry in the hippocampi of 1- to 21-day-old rats.
      Moreover, the temporal profile (from 30 min to 1 week) of MAP2 isoform reactivity
      to kainic acid-induced status epilepticus was studied in P9 rats. During
      development, the expression of the high-molecular weight MAP2 isoforms
      significantly increased, while the low-molecular weight isoforms decreased, the
      most prominent changes occurring during the second postnatal week. This
      developmental increase in the high-molecular weight MAP2 expression was also
      confirmed with immunocytochemistry, which showed increased immunoreactivity,
      particularly in the molecular layers of the dentate gyrus, and in CA1 and CA3
      stratum radiatum. In 9-day-old rats, status epilepticus resulted in a rapid
      transient increase (about 210%) in the high-molecular weight MAP2 expression,
      without any effect on the low-molecular weight MAP2. Moreover, disturbed
      dendritic structure in the CA1 and CA3 stratum radiatum was manifested as
      formation of varicosities 3h after the kainic acid treatment. The strictly
      developmentally regulated MAP2 isoform expression suggests different functional
      roles for these proteins during the postnatal development in the rat hippocampus.
      Moreover, high-molecular weight MAP2s may play a role in nerve cell survival
      during cell stress.

PMID- 17229542
TI  - Depressed DHEA and increased sickness response behaviors in lame dairy cows with
      inflammatory foot lesions.
AB  - Lameness is a multifactorial condition influenced by the environment, genetics,
      management and nutrition. Detection of lameness is subjective and currently
      limited to visual locomotion observations which lack reliability and sensitivity.
      The objective of this study was to search for potential biomarkers of
      inflammatory foot lesions that underlie most cases of lameness in dairy cows,
      with a focus on the sickness response and relevant endocrine, immune and
      behavioral changes. Serum and peripheral blood mononuclear cells (PBMC) were
      collected from eight sound and eight lame high-producing Holstein cows. Immune
      cell activation was investigated in PBMCs using a candidate gene approach in
      which the expression of pro-opiomelanocortin, interleukin-1beta, l-selectin,
      matrix metalloproteinase-9 and glucocorticoid receptor-alpha was measured via
      quantitative real time-RT-PCR. Endocrine changes were investigated by monitoring
      serum concentrations of cortisol and dehydroepiandrosterone (DHEA). Additionally,
      systematic behavioral observations were carried out to characterize a behavioral
      profile associated with a sickness response typical of this condition. Lame cows
      showed significantly lower eating (P=0.01) and ruminating (P=0.01) behaviors and
      higher incidence of self-grooming (P=0.04) compared to sound cows. Lame cows also
      showed a 23% decrease in serum DHEA (P=0.01) and 65% higher cortisol:DHEA ratio
      (P=0.06) compared to sound cows. However, no significant differences were found
      in candidate gene expression between lame and sound cows. In association with
      sickness behaviors, serum DHEA concentration and cortisol:DHEA ratio are
      promising objective indicators of inflammatory foot lesions in dairy cattle and
      may be useful as diagnostic targets for animals in need of treatment.

PMID- 17229543
TI  - Identification of genes with correlated patterns of variations in DNA copy number
      and gene expression level in gastric cancer.
AB  - To identify DNA copy number changes that had a direct influence on mRNA
      expression in gastric cancer, cDNA microarray-based comparative genomic
      hybridization (aCGH) and gene expression profiling were performed using 17 K cDNA
      microarrays. A set of 158 genes showing Pearson correlation coefficients over 0.6
      between DNA copy number changes and mRNA expression level variations was
      selected. In an independent gene expression profiling of 60 tissue samples, the
      158 genes were able to distinguish most of the normal and tumor tissues in an
      unsupervised hierarchical clustering, suggesting that the differential expression
      patterns displayed by this specific group of genes are most likely based on the
      gene copy number changes. Furthermore, 43 statistically significant (P<0.01)
      genes were selected that correctly distinguished all of the tissue samples. The
      copy number changes detected by aCGH can be verified by fluorescence in situ
      hybridization and real-time polymerase chain reaction. The selected genes include
      those that were previously identified as being tumor suppressors or deleted in
      various tumors, including GATA binding protein 4 (GATA4), monoamine oxidase A
      (MAOA), cyclin C (CCNC), and oncogenes including malignant fibrous histiocytoma
      amplified sequence 1 (MFHAS1/MASL1), high mobility group AT-hook 2 (HMGA2), PPAR
      binding protein (PPARBP), growth factor receptor-bound protein 7 (GRB7), and TBC1
      (tre-2, BUB2, cdc16) domain family, member 1 (TBC1D1).

PMID- 17229544
TI  - An efficient method for producing an indexed, insertional-mutant library in rice.
AB  - Generation of an indexed, saturated, insertional-mutant library is an aid to
      understanding the functions of genes in an organism. However, 10 years of work by
      many investigators have not yet yielded such a library in rice. The major reason
      is that determining the chromosomal locations of a very large number of random
      insertion mutants by flanking sequence analysis is highly labor intensive, and
      therefore, libraries that do exist have not been indexed. We report here an
      efficient procedure to construct an indexed, region-specific, insertional-mutant
      library of rice. The procedure makes use of efficient long-PCR-based high
      throughput indexing, coupled with a random but anchored population of Ds
      transposants. Long-PCR indexing allows rapid and simultaneous determination of
      the chromosomal locations of a large number of mutants that surround a particular
      anchor line, thus converting a random library into an indexed one. Such a library
      can be used directly, without the need to screen a large random library for a
      desired mutant plant.

PMID- 17229545
TI  - Modulation of mammary tumor development in Tg.NK (MMTV/c-neu) mice by dietary
      fatty acids and life stage-specific exposure to phytoestrogens.
AB  - Breast cancer is a major public health problem among women worldwide.
      Phytoestrogens and dietary fat composition are being investigated to elucidate
      the role of nutrition in breast cancer risk. Both epidemiological and rodent
      studies suggest that the chemopreventive effect of phytoestrogens depends on
      timing of exposure. We investigated spontaneous mammary tumor development in
      female heterozygous MMTV/c-neu (Tg.NK) mice upon isoflavone exposure on
      background diets rich in either n-6 or n-3 polyunsaturated fatty acids (PUFAs).
      Three different exposure protocols were used, either from conception to weaning,
      or from weaning onwards, or lifelong. Mice fed diets high in n-3 PUFAs developed
      mammary tumors 15 weeks later than mice fed n-6 PUFA diets. In the latter mice,
      isoflavone exposure from weaning onwards resulted in a significant decrease in
      tumor incidence and a delay in tumor onset. Therefore, the effects of
      phytoestrogen exposure on tumor formation appear to depend on the composition of
      the background diet and on the timing of exposure within the life cycle.

PMID- 17229546
TI  - Palmitoylation of the TPbeta isoform of the human thromboxane A2 receptor.
      Modulation of G protein: effector coupling and modes of receptor internalization.
AB  - Palmitoylation is a prevalent feature amongst G protein-coupled receptors. In
      this study we sought to establish whether the TPalpha and TPbeta isoforms of the
      human prostanoid thromboxane (TX) A2 receptor (TP) are palmitoylated and to
      assess the functional consequences thereof. Consistent with the presence of three
      cysteines within its unique carboxyl-terminal domain, metabolic labelling and
      site-directed mutagenesis confirmed that TPbeta is palmitoylated at Cys347 and,
      to a lesser extent, at Cys373,377 whereas TPalpha is not palmitoylated.
      Impairment of palmitoylation did not affect TPbeta expression or its ligand
      affinity. Conversely, agonist-induced [Ca2+]i mobilization by TPbetaC347S and the
      non-palmitoylated TPbetaC347,373,377S, but not by TPbetaC373S or TPbetaC373,377S,
      was significantly reduced relative to the wild type TPbeta suggesting that
      palmitoylation at Cys347 is specifically required for efficient Gq/phospholipase
      Cbeta effector coupling. Furthermore, palmitoylation at Cys373,377 is critical
      for TPbeta internalization with TPbetaC373S, TPbetaC373,377S and
      TPbetaC347,373,377S failing to undergo either agonist-induced or temperature
      dependent tonic internalization. On the other hand, whilst TPbetaC347S underwent
      reduced agonist-induced internalization, it underwent tonic internalization to a
      similar extent as TPbeta. The deficiency in agonist-induced internalization by
      TPbetaC347S, but not by TPbetaC373,377 nor TPbeta(C347,373,377S), was overcome by
      over-expression of either beta-arrestin1 or beta-arrestin2. Taken together, data
      herein suggest that whilst palmitoylation of TPbeta at Cys373,377 is critical for
      both agonist- and tonic-induced internalization, palmitoylation at Cys347 has a
      role in determining which pathway is followed, be it by the beta-arrestin
      dependent agonist-induced pathway or by the beta-arrestin-independent tonic
      internalization pathway.

PMID- 17229547
TI  - The truncated ghrelin receptor polypeptide (GHS-R1b) acts as a dominant-negative
      mutant of the ghrelin receptor.
AB  - The dimerization properties of the ghrelin receptor (GRLN-R) and its non
      signalling, naturally occurring, truncated splice variant (GHS-R1b) have been
      investigated in human embryonic kidney 293 cells heterologously expressing these
      proteins. Using the techniques of bioluminescence resonance energy transfer and
      co-immunoprecipitation, we detected the formation of GRLN-R homodimers and GRLN
      R/GHS-R1b heterodimers, but ghrelin-induced conformational changes were only
      detected in the GRLN-R homodimers. When the expression of GHS-R1b exceeded that
      of GRLN-R, there was a decrease in the cell surface expression of GRLN-R with a
      consequent decrease in constitutive activation of phosphatidylinositol-specific
      phospholipase C (PI-PLC). Furthermore, there was no change in ghrelin affinity,
      and the efficacy of cell signalling as measured by stimulation of PI-PLC and
      extracellular signal-regulated kinase 1/2 was unchanged. Cellular localization
      studies suggest that GRLN-R is normally distributed between the plasma membrane
      and cytosolic fractions, but in the presence of GHS-R1b, GRLN-R is localized to
      the nucleus. Therefore, we propose that the decrease in GRLN-R constitutive
      signalling was due to translocation of GRLN-R to the nucleus due to the formation
      of GRLN-R/GHS-R1b heterodimers. Therefore, GHS-R1b appears to act as a dominant
      negative mutant of the full-length GRLN-R.

PMID- 17229548
TI  - Prophylaxis versus pre-emptive treatment for infective and inflammatory
      complications of surgical third molar removal: a randomized, double-blind,
      placebo-controlled, clinical trial with sustained release amoxicillin/clavulanic
      acid (1000/62.5 mg).
AB  - The most common complications after surgical extraction of the third mandibular
      molar are trismus, oedema or swelling, local pain, dysphagia and infection. The
      aim of this comparative, double-blind, randomized clinical trial was to evaluate
      the efficacy of two sustained release amoxicillin/clavulanate regimens in the
      reduction of infection after third molar extractive surgery. A total of 225
      patients were randomized into three equal groups: placebo, prophylaxis with
      single pre-surgical dose of two tablets amoxicillin/clavulanate 1000/62.5 mg, and
      pre-emptive post-surgery therapy with two tablets amoxicillin/clavulanate
      1000/62.5 mg BID for 5 days. A higher rate of infection (P=0.006) was found among
      patients receiving placebo (16%) than those receiving single-dose prophylaxis
      (5.3%) or 5-day pre-emptive therapy (2.7%). A relationship between both the
      duration (13.8% for long versus 7.4% for medium versus 1.6% for short) and
      difficulty (12.7% with ostectomy versus 3.5% without ostectomy; P=0.011) of
      surgical procedure and incidence of subsequent infection was also observed. Both
      prophylactic and therapeutic regimens versus placebo achieved greater reduction
      of pain after surgery on day 3 (P=0.001). Logistic regression analysis revealed a
      risk of infection of 24%, 9% and 4% for ostectomy with placebo, prophylaxis and
      pre-emptive treatment, respectively, whereas it was 7%, 2% and 1% if ostectomy
      was not performed. Pre-emptive therapy with the oral sustained release
      amoxicillin/clavulanate formulation reduced the rate of subsequent infection in
      patients undergoing ostectomy. Prophylaxis was beneficial in simpler procedures
      and may be indicated in cases where ostectomy is not performed.

PMID- 17229549
TI  - Removal of a pellet from the left orbital cavity by image-guided endoscopic
      navigation.
AB  - In the cranio-maxillofacial field, computer-aided surgery based on computed
      tomography data is becoming increasingly important. Complex surgical procedures
      can be performed utilizing preoperative imaging to provide real-time localization
      of surgical instruments in the surgical field. Image-data-based navigation plays
      an ever-increasing role in cases of minimal invasive surgery. The case is
      presented here of a 58-year-old male patient referred after a hunting accident
      with a pellet in the left orbit. After transferring the preoperatively acquired
      computed tomography data to a commercially available navigation system, the
      bullet was removed through the original wound canal using an intraoperatively
      calibrated high-resolution endoscope.

PMID- 17229551
TI  - Psoriasis in childhood with total remission x chronic disease: clinical
      application of HLA class I markers.

PMID- 17229550
TI  - Dissociable contributions of MRI volume reductions of superior temporal and
      fusiform gyri to symptoms and neuropsychology in schizophrenia.
AB  - We sought to identify the functional correlates of reduced magnetic resonance
      imaging (MRI) volumes of the superior temporal gyrus (STG) and the fusiform gyrus
      (FG) in patients with chronic schizophrenia. MRI volumes, positive/negative
      symptoms, and neuropsychological tests of facial memory and executive functioning
      were examined within the same subjects. The results indicated two distinct,
      dissociable brain structure-function relationships: (1) reduced left STG volume
      positive symptoms-executive deficits; (2) reduced left FG-negative symptoms
      facial memory deficits. STG and FG volume reductions may each make distinct
      contributions to symptoms and cognitive deficits of schizophrenia.

PMID- 17229552
TI  - Non-compliance with antibiotic therapy for acute community infections: a global
      survey.
AB  - A global patient survey of non-compliance with antibiotic therapy for acute
      community infections included 4514 adult respondents (aged 18-99 years) in 11
      countries. Admitted non-compliance (ANC) was reported in 912/4088 (22.3%) of
      cases but varied widely between countries. Multivariate analysis identified five
      independent variables associated with ANC: country, daily dosage regimen, age,
      attitudes to doctors and attitudes to antibiotics. ANC ranged from 44.0% in China
      to 9.9% in The Netherlands, and from 14.9% in those prescribed once-daily
      regimens to 27.0% for three or more daily doses. There was a negative correlation
      between ANC and age. Analysis of the attitudes to doctors confirmed previous
      findings that involving the patient in the management of their infection can
      improve overall compliance. The study identified seven key attitudes to
      antibiotic use with the potential to improve compliance. However, there was a
      poor understanding in 10 of the 11 countries of how non-compliance can increase
      the potential for resistance development. Segmentation and cluster analysis
      identified four psychographic profiles influencing compliant behaviour, which
      varied across countries. The global picture of antibiotic non-compliance and
      psychographic profiling should help identify areas for targeted, country-specific
      patient educational programmes as well as those areas where physicians can
      improve their interaction with their patients.

PMID- 17229553
TI  - In vitro activities of tigecycline, daptomycin, linezolid and
      quinupristin/dalfopristin against glycopeptide-resistant Enterococcus faecium.

PMID- 17229554
TI  - VIM-1-producing Klebsiella pneumoniae bloodstream infections: analysis of 28
      cases.

PMID- 17229555
TI  - Linezolid-based therapy in Staphylococcus epidermidis endocarditis.

PMID- 17229556
TI  - Tetracycline resistance and distribution of tet genes in members of the
      Staphylococcus sciuri group isolated from humans, animals and different
      environmental sources.

PMID- 17229558
TI  - [Evaluation of vaccine coverage in children from 2 to 4 years old in South
      Eastern France].
AB  - BACKGROUND: Few studies have evaluated vaccination coverage in early childhood in
      South-Eastern France and spatial and social factors associated to it. POPULATION
      AND METHODS: We carried out a study in children aged 3.5-4.5 years and attending
      112 nursery schools randomly selected in South-Eastern France. Data were
      collected in 2002-2003 during a mandatory health assessment by physicians and
      nurses of the services of maternal and infant protection, who completed a new
      questionnaire developed to standardise these examinations in the whole region.
      RESULTS: Among the 2959 selected children, 2460 (83.1%) could be included in the
      study; out of them, 96.4% had been vaccinated against diphtheria and tetanus,
      95.0% against poliomyelitis, 92.8% against pertussis, 89.3% against haemophilus
      influenzae type b and 96.5% against tuberculosis. Vaccination rates at the age of
      18 months including the first booster were less important than vaccination rates
      for children aged 3.5-4.5 years. Only 24.3% of the children had been vaccinated
      against hepatitis B and 86.4% against measles-mumps-rubella. Vaccination rates at
      the age of 2, were significantly higher on the basis of the health certificates
      of the 24th month (CS24) than on the basis of our study. Vaccination rates were
      highest in urban areas and those with educational priority. CONCLUSION:
      Vaccination rates at the age of 3.5-4.5 years are satisfying but rates for the
      first booster should be improved. Vaccination rates against hepatitis B were low
      when those against MMR do not reach the WHO recommended level of 95.0%. Our
      results suggest that the analysis of data from the CS24 overestimates the real
      vaccination coverage at this age in South-Eastern France.

PMID- 17229559
TI  - [Management of childhood idiopathic thrombocytopenic purpura: a survey of members
      of the French Society of Pediatric Hematology and Immunology (SHIP)].
AB  - AIM OF THE STUDY: The purpose of this study was to report in acute childhood
      idiopathic thrombocytopenic purpura (ITP) the current practices of French
      paediatric hematologists and to compare them to recent publications of American
      and British teams. METHOD: A questionnaire was sent online to the members of the
      French Society of Pediatric Hematology/Immunology (SHIP). This questionnaire,
      adapted from a similar american study conducted in 2001, asked 16 questions based
      on the clinical presentation of a 5-year-old boy referred for an acute ITP.
      RESULTS: 59/123 SHIP members responded to the survey. In response to question
      regarding initial treatment, 86% of physicians would be given active treatments
      and only 9% would rarely or never administer any drug. When asked which agent
      would be used in case of treatment, 68% would choose to prescribe intravenous
      immunoglobulins and 32% corticosteroids, nobody recommended the use of anti-D
      immunoglobulins. Furthermore, 83% would usually hospitalize such a child.
      CONCLUSION: Finally, this study allowed us to update the current French
      management of treating pediatric ITP which is almost comparable among this subset
      of pediatric hematologists, but showed some discrepancies comparatively to the
      American and British studies.

PMID- 17229557
TI  - Cell cycle molecules define a pathway required for neuron death in development
      and disease.
AB  - We review here evidence defining a molecular pathway that includes cell cycle
      related molecules and that appears to play a required role in neuron death during
      normal development as well as in disease and trauma. The pathway starts with
      inappropriate activation of cyclin dependent kinase 4 (Cdk4) in neurons which
      leads to hyper-phosphorylation of the pRb family member p130. This in turn
      results in dissociation of p130 and its associated chromatin modifiers Suv39H1
      and HDAC1 from the transcription factor E2F4. Dissociation of this complex
      results in de-repression of genes with E2F binding sites including those encoding
      the transcription factors B- and C-Myb. Once elevated in neurons, B- and C-Myb
      proteins bind to the promoter for the pro-apoptotic BH3-only protein Bim and
      promote its induction. Bim then interacts with the core cellular apoptotic
      machinery, leading to caspase activation and apoptotic death. This pathway is
      supported by a variety of observations and experimental findings that implicate
      it as a required element for neuron loss in development and in many nervous
      system traumas and disorders. The components of this pathway appear to represent
      potential therapeutic targets for prevention of disease-associated neuron death.

PMID- 17229560
TI  - [The mutation 35delG of the gene of the connexin 26 is a frequent cause of
      autosomal-recessive non-syndromic hearing loss in Morocco].
AB  - Mutations of the connexin 26 gene, GJB2, are the most common cause of non
      syndromic autosomal-recessive hearing loss. One of the GJB2 mutations, the
      35delG, is recurrent in European and Mediterranean populations with allelic
      frequency of at least 70% in patients with hearing loss caused by GJB2
      impairment. OBJECTIVES: To determine the prevalence of the 35delG mutation in non
      syndromic autosomal-recessive deafness in Morocco. PATIENTS AND METHODS: We
      looked for the 35delG mutation among 25 non-related Moroccan children suffering
      from an autosomal recessive hearing loss. A screening for GJB2 mutations, and
      then a search for GJB6 deletions were carried out among patients who do not bear
      the 35delG. RESULTS: Twelve patients were homozygous for the 35delG mutation.
      This mutation was responsible for almost half of the hearing loss among our
      patients (48%). There was no other GJB2 or GJB6 mutation among 13 patients.
      CONCLUSION: This study underlines the advantages of a systematic search for this
      mutation among deaf children when environmental causes are considered irrelevant.
      The identification of this genetic anomaly signs the etiologic diagnosis of
      deafness, which allows a relevant genetic advice, and a better treatment of
      patients.

PMID- 17229561
TI  - The effect of n-3 PUFA on eNOS activity and expression in Ea hy 926 cells.
AB  - The aim of this study was to evaluate the effects of eicosapentaenoic acid (EPA)
      and docosahexaenoic acid (DHA) on NO synthase (eNOS) activation in Ea hy 926
      endothelial cells. EPA or DHA (0-80 microM), added to the culture medium during
      24h, were dose-dependently incorporated into the cells. In control medium, eNOS
      activity (evaluated by the citrulline assay) and eNOS phosphorylation on Ser 1177
      were correlated. They were increased by 10 microM histamine and prevented by 20
      microM lysophosphatidylcholine (LPC). By contrast, EPA or DHA increased basal
      phosphorylation without affecting eNOS activity in non-stimulated cells, but dose
      dependently decreased this activity in histamine-stimulated cells without
      modifying the phosphorylation level. Furthermore, EPA and DHA did not prevent the
      deleterious effects of LPC on histamine stimulation. In conclusion, incorporation
      of EPA and DHA could be deleterious for endothelial cells by deregulating the
      activation of eNOS and preventing NO liberation.

PMID- 17229562
TI  - Diffusing capacity for nitric oxide: reference values and dependence on alveolar
      volume.
AB  - Nitric oxide (NO) has a much stronger affinity for hemoglobin than carbon
      monoxide (CO); therefore, the DL(NO) (diffusing capacity for NO) is less
      influenced by changes in capillary blood volume than the DL(CO) (diffusing
      capacity for CO), and represents the true membrane diffusing capacity. We
      measured the combined single breath DL(NO)/DL(CO) in 124 healthy subjects, and
      generated reference equations for the DL(NO) and K(NO). In a subset of 21
      subjects the measurements were performed on different inspiratory levels. The
      reference equation for DL(NO) in females is 53.47*H(height)0.077*A(age)
      48.28(RSD5.22) and for males 59.84*H-0.25*A-44.20(RSD6.39). Reference equations
      for K(NO) in females is -2.03*H-0.025*A+11.52(RSD0.48) and for males -0.15*H
      0.045*A+9.47(RSD0.65). The K(CO) (DL(CO)/V(A)) increases when V(A) (alveolar
      volume) decreases, probably due to an increase of blood volume per unit lung
      volume. The DL(NO) was much stronger related to the V(A), the K(NO) was almost
      independent of V(A). Because of the relative independence of the K(NO) on V(A),
      the K(NO) appears to be a much better index for the diffusion capacity per unit
      lung volume (transfer coefficient) than the K(CO).

PMID- 17229563
TI  - Effect of formoterol and salmeterol on IL-6 and IL-8 release in airway epithelial
      cells.
AB  - Beta(2)-adrenoceptors are widely distributed and occur on airway epithelial
      cells. The aim of this study was to find out whether the two long-acting beta(2)
      agonists formoterol and salmeterol influence interleukin-6 (IL-6) and -8 (IL-8)
      release from airway epithelial cells in vitro. A549 cells and primary bronchial
      epithelial cells (PBEC) were stimulated with organic dust from pig barns. Non
      stimulated and dust-stimulated cells were incubated for 24h with formoterol or
      salmeterol (10(-13)-10(-6)M) and the release of IL-6 and IL-8 into the medium was
      assessed by ELISA technique. Propranolol (10(-5)M) or sotalol (10(-3)M) were used
      to block the beta(2)-agonist mediated effects. Formoterol and salmeterol both
      induced enhancement of IL-6 and IL-8 release and added to the effect of organic
      dust. This enhanced release was blocked by a beta-blocker in PBEC but not in A549
      cells. To our knowledge, this is the first time beta(2)-agonists have been shown
      to stimulate IL-6 release from airway epithelial cells. The results indicate
      different mechanisms of beta(2)-agonist action in bronchial and alveolar
      epithelial cells. Furthermore, our results indicate that A549 cells do not
      possess functional beta(2)-adrenoceptors.

PMID- 17229564
TI  - Development of a TIRF-based biosensor for sensitive detection of progesterone in
      bovine milk.
AB  - A total internal reflectance fluorescence (TIRF)-based biosensor for progesterone
      in bovine milk was developed and tested by measuring the progesterone level in
      daily milk samples for 25 days, covering a whole estrus cycle. The detection is
      based on total internal reflectance fluorescence. The assay has been designed as
      a binding-inhibition test with a progesterone derivative covalently immobilized
      on the sensor surface and a monoclonal anti-progesterone antibody as biological
      recognition element. First an existing progesterone assay was optimized by
      reducing the assay time per measurement, resulting in an assay time of about 5
      min and reaching a limit of detection (LOD) of 0.04 ng mL(-1) and a
      quantification limit (LOQ) of 0.34 ng mL(-1). After calibration the assay was
      tested by measuring the progesterone level in daily milk samples over several
      weeks. An estrus cycle of a cow could be measured. As results become available
      within minutes without any preparation or pre-concentration of the milk samples
      the fully automated TIRF-based biosensor for progesterone can be used in-line in
      the milking parlor and thus could be an important tool for reproductive
      management of dairy cattle detecting heat and predicting pregnancy, which are
      critical parameters in milk production.

PMID- 17229565
TI  - Anti-rabbit immunoglobulin G detection in complex medium by PM-RAIRS and QCM
      Influence of the antibody immobilisation method.
AB  - Two antibody immobilisation procedures were compared to set up an immunosensor
      for goat anti-rabbit immunoglobulin (anti-rIgG), i.e. rIgG covalently bound or
      immobilised via affinity to protein A (PrA). In both cases, the first layer of
      protein was covalently bound to a mixed self-assembled monolayer (SAM) of
      mercaptoundecanoic acid (MUA) and mercaptohexanol (C6OH) on a gold surface. The
      elaboration of the sensitive surfaces, as well as their selectivity and
      sensitivity were studied step by step by polarization modulation-reflection
      absorption infra-red spectroscopy (PM-RAIRS) and quartz crystal microbalance
      (QCM) with impedance measurement. QCM measurements showed that the viscoelastic
      properties of the antibody layer were markedly modified during the antigen
      recognition when the antibody was bound by affinity to PrA. The specific
      detection of antigen within a complex medium was assessed by PM-RAIRS thanks to
      the grafting of cobalt-carbonyl probes. Affinity constants between the
      immobilised rIgG and the anti-rIgG were determined from PM-RAIRS analysis.

PMID- 17229566
TI  - A new principle photosynthesis capacity biosensor based on quantitative
      measurement of delayed fluorescence in vivo.
AB  - Delayed fluorescence (DF) is an excellent marker for evaluating plant
      photosynthesis. Compared with common methods for measuring the photosynthesis
      rate based on consumption of CO(2), DF technique can quantify the plant
      photosynthesis capacity more accurately and faster under its physiological status
      with less interference from the environment. We previously reported a method for
      measuring photosynthesis using DF of chloroplast [Wang, C.L., Xing, D., Chen, Q.,
      2004. Biosens. Bioelectron. 20, 454-459]. In the study, a novel fast and portable
      photosynthesis capacity biosensor system was developed, which was composed of
      light-emitting diode lattice as excitation light source, Channel Photomultiplier
      DC-Module to achieve DF, single-chip microcomputer as control center, hermetic
      dark sample chamber, battery power supply and CO(2), humidity and temperature
      controller. Compared with our previous work, the system was portable and can
      directly measure plant photosynthesis capacity in vivo in less than 10s. A
      database in the software to carry out data acquisition and processing was
      developed to translate maximal DF intensity to net photosynthesis rate (Pn). In
      addition, local-control and remote-control mode can be chosen in the system. To
      demonstrate the utility of the system, it was applied to evaluate maximum Pn of
      four different plant species samples (Queen Rape Myrtle (var. rubra), soybean (Lu
      Hei No. 1), maize (Jin Dan No. 39) and rice (Jing Dao No. 21)) in field. The
      results were compared with that using commercial photosynthesis system LI-6400
      and the uncertainty was less than +/-5%. The new principle of photosynthesis
      measurement is a challenge and breakthrough to conventional method of gas
      exchange and may be a potential technique of next generation photosynthesis
      measurement.

PMID- 17229567
TI  - One step processing of aminofunctionalized gate oxides.
AB  - A plasma discharge process has been developed that allows the growth of biosensor
      gate oxides with adapted surface properties for the direct application of
      biomolecular immobilization cascades. The process involves an accurate selection
      of processing conditions, mainly, low temperature evaporation of (3
      aminopropyl)triethoxysilane (APTS) and dynamic power and flow conditions. Room
      temperature evaporation of APTS was achieved by designing a vessel with an
      internal capillary network. The initial high power (100 W) plasma conditions were
      replaced by milder molecular fragmentation (50 W, 25 W) in a pure Ar discharge.
      Under these conditions the thin SiO(2) layers presented graded properties with a
      denser layer at the Si (100) interface and a hybrid organic-inorganic structure
      at the surface. The chemistry of the films was analysed by Fourier transformed
      infrared spectroscopy (FTIR) and Rutherford backscattering spectroscopy combined
      with elastic recoil detection analysis (RBS, ERDA), which confirmed the presence
      of the SiO(2) and organic phases. Contact angle measurements indicate the higher
      contribution of the basic polar component to the surface free energy.
      Furthermore, the higher affinity of the surface towards biomolecular
      immobilization was confirmed by fluorescence microscopy. Finally, penetration of
      nitrobenzaldehyde was obtained by application of a molecular permeation method
      evaluated by UV-vis spectroscopy onto fused silica substrates.

PMID- 17229568
TI  - Synaptic development: insights from Drosophila.
AB  - In Drosophila, the larval neuromuscular junction is particularly tractable for
      studying how synapses develop and function. In contrast to vertebrate central
      synapses, each presynaptic motor neuron and postsynaptic muscle cell is unique
      and identifiable, and the wiring circuit is invariant. Thus, the full power of
      Drosophila genetics can be brought to bear on a single, reproducibly
      identifiable, synaptic terminal. Each individual neuromuscular junction
      encompasses hundreds of synaptic neurotransmitter release sites housed in a chain
      of synaptic boutons. Recent advances have increased our understanding of the
      mechanisms that shape the development of both individual synapses--that is, the
      transmitter release sites including active zones and their apposed glutamate
      receptor clusters--and the whole synaptic terminal that connects a pre- and post
      synaptic cell.

PMID- 17229569
TI  - Season of diagnosis is a predictor of cancer survival. Sun-induced vitamin D may
      be involved: a possible role of sun-induced Vitamin D.
AB  - The calcidiol level in a group of Norwegians (14,000 individuals, age range 16
      80) was found to be highest in late summer. The seasonal variation was larger for
      young than for old persons. The calcitriol concentration was practically constant
      throughout the year. Younger persons had less calcidiol and more calcitriol than
      older persons, indicating that the conversion of calcidiol to calcitriol is more
      efficient in younger persons. A seasonal variation of prognosis of cancer (colon
      , breast-, prostate- cancer and Hodgkin lymphoma) was found. The survival is
      highest for summer and autumn diagnosis, corresponding to maximal calcidiol
      levels. Thus, calcidiol may act synergistically with traditional treatment
      modalities. In view of these calcitriol and calcidiol data, the seasonal
      variation of cancer survival may be related to the calcidiol gradient, indicating
      that this Vitamin D metabolite may be more important than believed so far.

PMID- 17229570
TI  - Sequential regulation of keratinocyte differentiation by 1,25(OH)2D3, VDR, and
      its coregulators.
AB  - Keratinocyte differentiation requires the sequential regulation of gene
      expression. We have explored the role of 1,25(OH)(2)D(3) and its receptor (VDR)
      in this process. VDR sequentially binds to coactivator complexes such as Vitamin
      D receptor interacting protein (DRIP) and steroid receptor coactivator (SRC)
      during differentiation. Different genes respond differently to the
      VDR/coactivator complexes as determined by knockdown studies. The binding of
      DRIP205 and SRC to VDR is ligand (i.e. 1,25(OH)(2)D(3)) dependent. LXXLL motifs
      in these coactivators are critical for this binding; however, the affinity for
      VDR of the different LXXLL motifs in these coactivators varies. Hairless is an
      inhibitor of 1,25(OH)(2)D(3) dependent gene transcription. A phiXXphiphi motif in
      hairless is crucial for hairless binding to VDR, and its binding is ligand
      independent. 1,25(OH)(2)D(3) displaces hairless and recruits the coactivators to
      VDREs. Hsp90 and p23 are chaperone proteins recruited to the DRIP/VDR complex,
      where they block the binding of the complex to VDREs and block 1,25(OH)(2)D(3)
      stimulated transcription. Thus four mechanisms explain the ability of
      1,25(OH)(2)D(3) to sequentially regulate gene transcription during
      differentiation: changes in coregulator levels, their differential binding to
      VDR, differential gene responsiveness to the VDR/coregulator complexes, and
      chaperone proteins facilitating the cycling of VDR/coregulator complexes on and
      off the VDREs.

PMID- 17229571
TI  - Novel pathways that contribute to the anti-proliferative and chemopreventive
      activities of calcitriol in prostate cancer.
AB  - Calcitriol, the hormonally active form of Vitamin D, inhibits the growth and
      development of many cancers through multiple mechanisms. Our recent research
      supports the contributory role of several new and diverse pathways that add to
      the mechanisms already established as playing a role in the actions of calcitriol
      to inhibit the development and progression of prostate cancer (PCa). Calcitriol
      increases the expression of insulin-like growth factor binding protein-3 (IGFBP
      3), which plays a critical role in the inhibition of PCa cell growth by
      increasing the expression of the cell cycle inhibitor p21. Calcitriol inhibits
      the prostaglandin (PG) pathway by three actions: (i) the inhibition of the
      expression of cyclooxygenase-2 (COX-2), the enzyme that synthesizes PGs, (ii) the
      induction of the expression of 15-prostaglandin dehydrogenase (15-PGDH), the
      enzyme that inactivates PGs and (iii) decreasing the expression of EP and FP PG
      receptors that are essential for PG signaling. Since PGs have been shown to
      promote carcinogenesis and progression of multiple cancers, the inhibition of the
      PG pathway may add to the ability of calcitriol to prevent and inhibit PCa
      development and growth. The combination of calcitriol and non-steroidal anti
      inflammatory drugs (NSAIDs) result in a synergistic inhibition of PCa cell growth
      and offers a potential therapeutic strategy. Mitogen activated protein kinase
      phosphatase 5 (MKP5) is a member of a family of phosphatases that are negative
      regulators of MAP kinases. Calcitriol induces MKP5 expression in prostate cells
      leading to the selective dephosphorylation and inactivation of the stress
      activated kinase p38. Since p38 activation is pro-carcinogenic and is a mediator
      of inflammation, this calcitriol action, especially coupled with the inhibition
      of the PG pathway, contributes to the chemopreventive activity of calcitriol in
      PCa. Mullerian Inhibiting Substance (MIS) has been evaluated for its inhibitory
      effects in cancers of the reproductive tissues and is in development as an anti
      cancer drug. Calcitriol induces MIS expression in prostate cells revealing yet
      another mechanism contributing to the anti-cancer activity of calcitriol in PCa.
      Thus, we conclude that calcitriol regulates myriad pathways that contribute to
      the potential chemopreventive and therapeutic utility of calcitriol in PCa.

PMID- 17229572
TI  - 1,25-Dihydroxyvitamin D3 induces expression of the Wnt signaling co-regulator
      LRP5 via regulatory elements located significantly downstream of the gene's
      transcriptional start site.
AB  - Canonical Wnt signaling is essential for bone formation. Activation involves
      binding of secreted members of the Wnt family of proteins with a membrane
      receptor Frizzled on osteoblasts, an interaction that is facilitated by LRP5/LRP6
      co-receptors. LRP5 is known to play a particularly important role in bone
      formation such that the loss of this protein results in a reduction in osteoblast
      number, a delay in mineralization and a reduction in peak BMD. During the course
      of a VDR ChIP-chip analysis we found that 1,25(OH)(2)D(3) could induce binding of
      the VDR to sites within the Lrp5 gene locus. Importantly, this interaction
      between 1,25(OH)(2)D(3)-activated VDR and the Lrp5 gene led to both a
      modification in chromatin structure within the Lrp5 locus and the induction of
      LRP5 mRNA transcripts in vivo as well as in vitro. One site within Lrp5 was
      discovered to confer 1,25(OH)(2)D(3) response to a heterologous promoter in
      osteoblastic cells, permitting both the identification and characterization of
      the component VDRE. While the regulatory region in Lrp5 was highly conserved in
      the human genome, the VDRE was not. Our studies show that 1,25(OH)(2)D(3) can
      enhance the expression of a critical component of the Wnt signaling pathway which
      is known to impact osteogenesis.

PMID- 17229573
TI  - The effect of excessive tibial torsion on the capacity of muscles to extend the
      hip and knee during single-limb stance.
AB  - Excessive tibial torsion, a rotational deformity about the long axis of the
      tibia, is common in patients with cerebral palsy who walk with a crouch gait.
      Previous research suggests that this deformity may contribute to crouch gait by
      reducing the capacity of soleus to extend the knee; however, the effects of
      excess external torsion on the capacity of other muscles to extend the stance
      limb during walking are unknown. A computer model of the musculoskeletal system
      was developed to simulate a range of tibial torsion deformities. A dynamic
      analysis was then performed to determine the effect of these deformities on the
      capacity of lower limb muscles to extend the hip and knee at body positions
      corresponding to the single-limb stance phase of a normal gait cycle. Analysis of
      the model confirmed that excessive external torsion reduces the extension
      capacity of soleus. In addition, our analysis revealed that several important
      muscles crossing the hip and knee are also adversely affected by excessive tibial
      torsion. With a tibial torsion deformity of 30 degrees , the capacities of
      soleus, posterior gluteus medius, and gluteus maximus to extend both the hip and
      knee were all reduced by over 10%. Since a tibial torsion deformity reduces the
      capacity of muscles to extend the hip and knee, it may be a significant
      contributor to crouch gait, especially when greater than 30 degrees from normal,
      and thus should be considered by clinicians when making treatment decisions.

PMID- 17229574
TI  - Frequency of local recurrence following segmentectomy of stage IA non-small cell
      lung cancer is influenced by segment localisation and width of resection margins-
      implications for patient selection for segmentectomy.
AB  - OBJECTIVE: Segmentectomy has recently been suggested as alternative to lobectomy
      for curative treatment of early-stage non-small cell lung cancer (NSCLC). This
      study was performed to investigate if localisation of the resected segment or
      width of resection margins influence local recurrence following complete
      segmentectomy of stage IA NSCLC. METHODS: Between 1987 and 2002, 49
      segmentectomies and 150 lobectomies were performed in patients with pT1pN0cM0
      NSCLC in our institution. Indications for segmentectomy were a limited pulmonary
      function or severe comorbidity. The median follow-up duration was 54 months.
      Local recurrence was distinguished from secondary primary lung cancer and was
      defined as tumour within the same lung or in the ipsilateral mediastinum. Segment
      localisation, width of resection margins, tumour size, tumour type, grading and
      age were analysed concerning their influence on local recurrence. RESULTS: Local
      recurrence occurred in 16% of patients with segmentectomy and was significantly
      more frequent than in patients with lobectomy (5%; p=0.005; log-rank test).
      Segmentectomy in the S1-3 region tended more frequently to local recurrence than
      segmentectomy in the remaining segments (p=0.08; log-rank test): There was no
      recurrence following segmentectomy in the S7-10 region (n=6) or of S4-5 (n=5).
      Recurrence occurred in 7 (23%) out of 30 patients with segmentectomy in the S1-3
      region and in 1 (12%) out of 8 patients with S6-segmentectomy. Also, resection
      margins < or = 1cm tended to be associated with local recurrence (p=0.06; log
      rank test). CONCLUSIONS: The frequency of local recurrence following
      segmentectomy might be influenced by segment localisation and width of resection
      margins. Segmentectomy within the S1-3 region should be avoided whenever
      possible.

PMID- 17229575
TI  - Ethyl acetate extract from Angelica Dahuricae Radix inhibits lipopolysaccharide
      induced production of nitric oxide, prostaglandin E2 and tumor necrosis factor
      alphavia mitogen-activated protein kinases and nuclear factor-kappaB in
      macrophages.
AB  - Angelica dahurica (Umbelliferae) has been used to treat headache of common cold,
      supraorbital neuralgia, painful swelling on the body, nasal stuffiness,
      leukorrhea and arthralgia due to wind-dampness in Korean traditional medicine. It
      is also claimed to be effective in the treatment of acne, erythema, headache,
      toothache, sinusitis, colds and flu. The present study focused whether the ethyl
      acetate extract from Angelica Dahuricae Radix (EAAD) inhibits production of
      nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumor necrosis factor (TNF)
      alpha, as well as expression of inducible nitric oxide synthase (iNOS),
      cyclooxygenase-2 (COX-2), nuclear factor-kappaB (NF-kappaB) and mitogen-activated
      protein kinases (MAPKs) in lipopolysaccharide (LPS)-stimulated macrophages. EAAD
      inhibited LPS-induced NO, PGE(2) and TNF-alpha production as well as expression
      of iNOS and COX-2 in RAW 264.7 cells. EAAD inhibited LPS-induced TNF-alpha
      production in THP-1 cells. Furthermore, EAAD suppressed LPS-induced
      phosphorylation of p38 MAPK and extracellular-signal regulated kinases 1/2
      (ERK1/2), I-kappaBalpha degradation, and NF-kappaB activation in RAW 264.7 cells.
      These results suggest that EAAD has the inhibitory effects on LPS-induced TNF
      alpha, NO and PGE(2) production, and expression of iNOS and COX-2 in macrophage
      through blockade in the phosphorylation of MAPKs, following I-kappaBalpha
      degradation and NF-kappaB activation.

PMID- 17229576
TI  - Effects of single amino acid substitution on the dissociation of multiply charged
      multiprotein complexes in the gas phase.
AB  - The effects of amino acid substitutions on the product ion charge distributions
      for protonated and deprotonated homogeneous and heterogeneous multiprotein
      complexes in the gas phase are studied using Fourier-transform mass spectrometry
      and the blackbody infrared radiative dissociation technique. Notably, it is shown
      that a single amino acid substitution in the leaving subunit can cause a small
      but measurable change in product ion charge distribution. Evidence that the
      degree of charge enrichment of the leaving subunit is influenced by the number of
      strongly basic or acidic residues within the subunit for the protonated and
      deprotonated complexes, respectively, is reported.

PMID- 17229577
TI  - Excitotoxicity in a chronic model of multiple sclerosis: Neuroprotective effects
      of cannabinoids through CB1 and CB2 receptor activation.
AB  - Inflammation, autoimmune response, demyelination and axonal damage are thought to
      participate in the pathogenesis of multiple sclerosis (MS). Understanding whether
      axonal damage causes or originates from demyelination is a crucial issue.
      Excitotoxic processes may be responsible for white matter and axonal damage.
      Experimental and clinical studies indicate that cannabinoids could prove
      efficient in the treatment of MS. Using a chronic model of MS in mice, we show
      here that clinical signs and axonal damage in the spinal cord were reduced by the
      AMPA antagonist, NBQX. Amelioration of symptomatology by the synthetic
      cannabinoid HU210 was also accompanied by a reduction of axonal damage in this
      model. Moreover, HU210 reduced AMPA-induced excitotoxicity both in vivo and in
      vitro through the obligatory activation of both CB1 and CB2 cannabinoid
      receptors. Together, these data underline the implication of excitotoxic
      processes in demyelinating pathologies such as MS and the potential therapeutic
      properties of cannabinoids.

PMID- 17229579
TI  - Internet-enabled high-resolution brain mapping and virtual microscopy.
AB  - Virtual microscopy involves the conversion of histological sections mounted on
      glass microscope slides to high-resolution digital images. Virtual microscopy
      offers several advantages over traditional microscopy, including remote viewing
      and data sharing, annotation, and various forms of data mining. We describe a
      method utilizing virtual microscopy for generation of internet-enabled, high
      resolution brain maps and atlases. Virtual microscopy-based digital brain atlases
      have resolutions approaching 100,000 dpi, which exceeds by three or more orders
      of magnitude resolutions obtainable in conventional print atlases, MRI, and flat
      bed scanning. Virtual microscopy-based digital brain atlases are superior to
      conventional print atlases in five respects: (1) resolution, (2) annotation, (3)
      interaction, (4) data integration, and (5) data mining. Implementation of virtual
      microscopy-based digital brain atlases is located at BrainMaps.org, which is
      based on more than 10 million megapixels (35 terabytes) of scanned images of
      serial sections of primate and non-primate brains with a resolution of 0.46
      microm/pixel (55,000 dpi). The method can be replicated by labs seeking to
      increase accessibility and sharing of neuroanatomical data. Online tools offer
      the possibility of visualizing and exploring completely digitized sections of
      brains at a sub-neuronal level and can facilitate large-scale connectional
      tracing, histochemical, and stereological analyses.

PMID- 17229578
TI  - Neuroanatomical correlates of personality in the elderly.
AB  - Extraversion and neuroticism are two important and frequently studied dimensions
      of human personality. They describe individual differences in emotional
      responding that are quite stable across the adult lifespan. Neuroimaging research
      has begun to provide evidence that neuroticism and extraversion have specific
      neuroanatomical correlates within the cerebral cortex and amygdala of young
      adults. However, these brain areas undergo alterations in size with aging, which
      may influence the nature of these personality factor-brain structure associations
      in the elderly. One study in the elderly demonstrated associations between
      perisylvian cortex structure and measures of self transcendence [Kaasinen, V.,
      Maguire, R.P., Kurki, T., Bruck, A., Rinne, J.O., 2005. Mapping brain structure
      and personality in late adulthood. NeuroImage 24, 315-322], but the
      neuroanatomical correlates of extraversion and neuroticism, or other measures of
      the Five Factor Model of personality have not been explored. The purpose of the
      present study was to investigate the structural correlates of neuroticism and
      extraversion in healthy elderly subjects (n=29) using neuroanatomic measures of
      the cerebral cortex and amygdala. We observed that the thickness of specific
      lateral prefrontal cortex (PFC) regions, but not amygdala volume, correlates with
      measures of extraversion and neuroticism. The results suggest differences in the
      regional neuroanatomic correlates of specific personality traits with aging. We
      speculate that this relates to the influences of age-related structural changes
      in the PFC.

PMID- 17229580
TI  - Monophasic action potential in anaesthetized guinea pigs as a biomarker for
      prediction of liability for drug-induced delayed ventricular repolarization.
AB  - INTRODUCTION: Drug-induced QT interval prolongation has been one of the critical
      issues for developing new chemical entities and pharmaceutical companies need to
      evaluate the risk early in the development stage. At such stage, guinea pigs are
      appropriate due to their small size requiring only small amounts of test drugs.
      The purpose of this study was to determine the utility of guinea pig monophasic
      action potential (MAP) using 12 reference drugs in order to clarify prediction of
      the QT interval prolonging risk. METHODS: Male guinea pigs were anaesthetized
      with pentobarbital (40 mg/kg, i.p.). Parameters analyzed were epicardial MAP
      duration (MAP(90)) at sinus rhythm (MAP(90(sinus))) and MAP(90) during atrial
      pacing (MAP(90(pacing))). Test drugs were administered to animals intravenously
      and cumulatively. RESULTS: Vehicle control did not affect the parameters tested.
      All 8 QT-prolonging drugs prolonged MAP(90(sinus)) and MAP(90(pacing)) dose
      dependently, whereas all 4 non-QT-prolonging drugs showed no or very slight
      prolongations of these MAP(90) parameters. Rank order potency of MAP(90(pacing))
      prolongations by the QT-prolonging drugs tended to correspond to clinical plasma
      concentrations associated with QT interval prolongations or Torsades de Pointes
      but showed less of a link with hERG inhibition activities. CONCLUSION: The
      present study demonstrates that the MAP model using anaesthetized guinea pigs
      could predict the liability of drugs for QT interval prolongation with high
      accuracy. QT assessment using the combination of the hERG assay with high
      sensitivity and the current in vivo assay would be desirable for early risk
      assessment within drug development.

PMID- 17229581
TI  - Isolation and characterization of the Omp-PA porin from Porphyromonas
      asaccharolytica, determination of the omp-PA gene sequence and prediction of Omp
      PA protein structure.
AB  - A single monomeric porin, Omp-PA (37kDa), was isolated from the outer membrane of
      the gram-negative anaerobic rod Porphyromonas asaccharolytica. Further
      characterization revealed that this porin consists of two different fractions: a
      heat-modifiable fraction which in its denatured form migrated on SDS-PAGE as a
      protein with a molecular weight of 41kDa and a heat-resistant fraction which did
      not change its migration on SDS-PAGE after boiling. A liposome swelling assay
      revealed that only the heat-resistant fraction was able to transport sugars after
      its incorporation into the liposomes, although it did not discriminate between
      differently sized sugars. We hypothesize that the heat-modifiable fraction
      corresponds to the "closed" conformer of Omp-PA, whereas the heat-resistant
      fraction corresponds to the "open" conformer of the protein. Cloning of the omp
      PA gene revealed an open reading frame of 1161 bases, with a predicted protein
      sequence of 387 amino acids. The mature protein consists of 366 amino acids with
      a calculated MW of 41,102Da and an estimated pI of 7.24. The C-terminal domain of
      Omp-PA is homologous to the characteristic OmpA signature domain (71% similarity
      with the OmpA consensus domain). Sequence comparison with other anaerobes from
      the Bacteroides family demonstrated homology across the entire ORF. Digestion of
      the P. asaccharolytica outer membrane analysis of trypsin-digested Omp-PA yielded
      two proteins migrating with apparent molecular weights of 37 and 27kDa. These
      data fully supported our hypothesis that the C-terminal domain of the two-domain
      "closed" conformer of Omp-PA was digested by trypsin, whereas the single domain
      beta-barrel "open" conformer was inaccessible to trypsin.

PMID- 17229582
TI  - Canine visceral leishmaniasis: relationships between clinical status, humoral
      immune response, haematology and Lutzomyia (Lutzomyia) longipalpis infectivity.
AB  - The main source of Leishmania infantum infection in humans is a naturally
      infected dog. This study reports on the infectivity to phlebotomine sandflies
      (Lutzomyia longipalpis) of serologically positive mongrel dogs that differed in
      clinical status, haematology and humoral responses to immunoglobulin (Ig) G(T)
      (total anti-Leishmania IgG), IgG(1) and IgG(2) subclasses of antibody to crude
      antigen of L. infantum. Forty-five female L. longipalpis were allowed to feed
      directly on the ears of dogs classified as asymptomatic, oligosymptomatic or
      symptomatic before being dissected five days later. Promastigotes were detected
      in 88% of the dissected sandflies. The highest rate of infectivity to sandflies
      was found in symptomatic dogs, followed by oligosymptomatic and asymptomatic
      animals. The results suggest that dogs naturally infected with L. infantum with
      higher total IgG and IgG(2) concentrations and lower haematocrit levels were able
      to infect the highest proportion of L. longipalpis. No correlation was observed
      between anaemia and the intensity of clinical signs. Symptomatic dogs presented
      the highest infection rate and intensity of infection.

PMID- 17229583
TI  - A new methodology for the simulation of flexible protein-ligand interactions.
AB  - A methodology has been developed for the simulation of induced fit between a
      ligand and its target protein. It utilizes constrained molecular dynamics where
      atoms determined to be immobile from difference distance matrix studies are
      fixed. Application of this methodology to HIV-1 reverse transcriptase (RT) as the
      example target protein has demonstrated its robustness. Short simulation times
      are sufficient to achieve good refinement of docking poses resulting from
      exchange of structurally dissimilar inhibitors between crystal structures.

PMID- 17229584
TI  - Proteometric study of ghrelin receptor function variations upon mutations using
      amino acid sequence autocorrelation vectors and genetic algorithm-based least
      square support vector machines.
AB  - Functional variations on the human ghrelin receptor upon mutations have been
      associated with a syndrome of short stature and obesity, of which the obesity
      appears to develop around puberty. In this work, we reported a proteometrics
      analysis of the constitutive and ghrelin-induced activities of wild-type and
      mutant ghrelin receptors using amino acid sequence autocorrelation (AASA)
      approach for protein structural information encoding. AASA vectors were
      calculated by measuring the autocorrelations at sequence lags ranging from 1 to
      15 on the protein primary structure of 48 amino acid/residue properties selected
      from the AAindex database. Genetic algorithm-based multilinear regression
      analysis (GA-MRA) and genetic algorithm-based least square support vector
      machines (GA-LSSVM) were used for building linear and non-linear models of the
      receptor activity. A genetic optimized radial basis function (RBF) kernel yielded
      the optimum GA-LSSVM models describing 88% and 95% of the cross-validation
      variance for the constitutive and ghrelin-induced activities, respectively. AASA
      vectors in the optimum models mainly appeared weighted by hydrophobicity-related
      properties. However, differently to the constitutive activity, the ghrelin
      induced activity was also highly dependent of the steric features of the
      receptor.

PMID- 17229585
TI  - [In favour of a conservative surgical treatment of ectopic pregnancies].

PMID- 17229586
TI  - Accuracy of high-resolution peripheral quantitative computed tomography for
      measurement of bone quality.
AB  - The introduction of three-dimensional high-resolution peripheral in vivo
      quantitative computed tomography (HR-pQCT) (XtremeCT, Scanco Medical,
      Switzerland; voxel size 82 microm) provides a new approach to monitor micro
      architectural bone changes longitudinally. The accuracy of HR-pQCT for three
      important determinants of bone quality, including bone mineral density (BMD),
      architectural measurements and bone mechanics, was determined through a
      comparison with micro-computed tomography (microCT) and dual energy X-ray
      absorptiometry (DXA). Forty measurements from 10 cadaver radii with low bone mass
      were scanned using the three modalities, and image registration was used for 3D
      data to ensure identical regions were analyzed. The areal BMD of DXA correlated
      well with volumetric BMD by HR-pQCT despite differences in dimensionality (R(2) =
      0.69), and the correlation improved when non-dimensional bone mineral content was
      assessed (R(2) = 0.80). Morphological parameters measured by HR-pQCT in a
      standard patient analysis, including bone volume ratio, trabecular number,
      derived trabecular thickness, derived trabecular separation, and cortical
      thickness correlated well with muCT measures (R(2) = 0.59-0.96). Additionally,
      some non-metric parameters such as connectivity density (R(2) = 0.90) performed
      well. The mechanical stiffness assessed by finite element analysis of HR-pQCT
      images was generally higher than for microCT data due to resolution differences,
      and correlated well at the continuum level (R(2) = 0.73). The validation here of
      HR-pQCT against gold-standards microCT and DXA provides insight into the accuracy
      of the system, and suggests that in addition to the standard patient protocol,
      additional indices of bone quality including connectivity density and mechanical
      stiffness may be appropriate to include as part of a standard patient analysis
      for clinical monitoring of bone quality.

PMID- 17229587
TI  - Understanding sample size: what determines the required number of microarrays for
      an experiment?
AB  - DNA microarray experiments have become a widely used tool for studying gene
      expression. An important, but difficult, part of these experiments is deciding on
      the appropriate number of biological replicates to use. Often, researchers will
      want a number of replicates that give sufficient power to recognize regulated
      genes while controlling the false discovery rate (FDR) at an acceptable level.
      Recent advances in statistical methodology can now help to resolve this issue.
      Before using such methods it is helpful to understand the reasoning behind them.
      In this Research Focus article we explain, in an intuitive way, the effect sample
      size has on the FDR and power, and then briefly survey some recently proposed
      methods in this field of research and provide an example of use.

PMID- 17229588
TI  - Association of cooking oil fumes exposure with lung cancer: involvement of
      inhibitor of apoptosis proteins in cell survival and proliferation in vitro.
AB  - Cooking oil fumes (COF) have been shown to be associated with lung cancer
      incidence in Chinese women. Our recent report indicates that inhibitor of
      apoptosis protein 2 (IAP2) induced by COF may contribute to the survival and
      proliferation of A549 lung cancer cells. In this study, to further verify whether
      other antiapoptosis proteins including IAP1, X-linked IAP (XIAP), and survivin,
      were linked with lung cancer cell survival and proliferation, these IAPs
      expressions in A549 cells after treatment with COF and its two major components,
      benzo[a]pyrene (BaP) and 2,4-decadienal (2,4-DDE) were evaluated by Western
      blotting. Our data showed that IAP2 was significantly induced by COF, BaP, and
      2,4-DDE, but XIAP was decreased by COF and 2,4-DDE, but not by BaP. Even though
      different effects of COF and 2,4-DDE on IAP2 and XIAP protein expressions were
      observed, the caspase-3 expression was diminished by COF and 2,4-DDE. In
      addition, induction of IAP2 and phosphorylated Akt proteins by COF and 2,4-DDE
      were simultaneously abolished by LY294002. Flow cytometry and terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis
      showed that the proportion of A549 cells at the S-phase was increased
      significantly after treatment with COF or 2,4-DDE. The cell proliferation induced
      by COF is associated with the attenuation of p21(Cip/Waf1) expression. Therefore,
      increases of IAP1, IAP2, survivin, and cyclin D1 expressions and decreases of
      XIAP, caspase-3, and p21 expressions might partly contribute to the survival and
      proliferation of lung cancer cells after exposure to 2,4-DDE and COF. In
      conclusion, the lung cancer cell growth promoted by COF might support previous
      epidemiological reports indicating that exposure of COF was associated with lung
      cancer development among Chinese women.

PMID- 17229589
TI  - Prospective comparison of R-mix shell vial system with direct antigen tests and
      conventional cell culture for respiratory virus detection.
AB  - BACKGROUND AND OBJECTIVES: Conventional cell culture (CC) has limited clinical
      utility as a result of the extended incubation period often required for virus
      isolation. Alternative methodologies have been introduced in an effort to improve
      turnaround times. One such system, the R-mix shell vial is discussed herein. The
      study objectives were: (a) to establish R-mix testing parameters as compared to
      direct antigen testing (DAT) and CC, and (b) to assess technical aspects and cost
      of R-mix in a high volume clinical virology laboratory. STUDY DESIGN: A
      prospective analysis of respiratory samples submitted to the clinical virology
      laboratory between November 2004 and April 2005 was performed. All specimens were
      inoculated onto R-mix shell vials (SV) and CC tubes; and a subset also underwent
      DAT for influenza A and B and/or RSV. A retrospective estimated cost analysis was
      made. RESULTS: A total of 563 samples were included in the study, which
      collectively revealed a total of 207 viruses. Sensitivity of R-mix for seven
      major respiratory viruses ranged from 45% to 83% compared to CC and DAT, while
      mean time to detection (TTD) varied from 1.1 to 1.4 days. In addition to these
      viruses, 23 picornaviruses, 11 CMV isolates and 5 HSV isolates were detected by
      CC alone. CONCLUSIONS: The R-mix system has similar sensitivity as CC for the
      detection of parainfluenza 1-3 and influenza A/B while dramatically reducing the
      TTD. Furthermore, it is significantly more sensitive and produces more timely
      results for RSV than CC; yet, neither method offers a diagnostic benefit over
      rapid DAT for RSV detection. The sensitivity of R-mix for adenovirus appears to
      be significantly lower than that of CC. Lastly, methodologies other than R-mix
      must remain in place under circumstances where identification of other potential
      viral respiratory pathogens, including herpesviruses and picornaviruses, is
      desired.

PMID- 17229590
TI  - Changing views on Langerhans cell functions in leishmaniasis.
AB  - The different functions of skin dendritic cell subsets during Leishmania
      infection were recently reviewed by Ritter and Osterloh. In their article, they
      propose a new role for epidermal Langerhans cells and dermal dendritic cells to
      explain the events that take place after inoculation by Leishmania.

PMID- 17229591
TI  - Schistosomiasis and malaria: another piece of the crossreactivity puzzle.
AB  - The recent discovery that individuals living in endemic areas have antibodies in
      their sera that are crossreactive for both helminth and malaria parasites raises
      important questions both of the interpretation of existing immunoepidemiological
      data and of the basic biology of the host and the parasites. One such shared
      antigen (SmLRR) has now been cloned and has, therefore, opened up an intriguing
      and exciting field of research for immunologists and parasitologists.

PMID- 17229592
TI  - Effects of the fungicide prochloraz on the sexual development of zebrafish (Danio
      rerio).
AB  - Some chemicals have the potential to adversely affect sexual development through
      multiple endocrine actions. Prochloraz is an imidazole fungicide that displays
      diverse mechanisms of action, including inhibition of aromatase activity,
      inhibition of androgen synthesis, and antagonism of the androgen receptor. The
      objective of this study was to assess the effects of prochloraz on the sexual
      development of zebrafish (Danio rerio) in the Fish Sexual Development Test (FSDT)
      proposed as an OECD test guideline for detection of endocrine disruptors.
      Zebrafish were exposed to prochloraz (0, 16, 64 or 202 microg/L) for 60 days from
      24 h post fertilization. Fish exposed to 202 microg/L prochloraz showed an
      increased proportion of males. Furthermore, the incidence of intersex and the
      stages of the gonads were altered in the treated fish compared to the control
      fish. A significant vitellogenin decrease was observed in both female and male
      zebrafish at an exposure concentration of 202 microg/L prochloraz. However, in
      the male fish, significantly increased vitellogenin concentrations were observed
      in the groups exposed to 16 or 64 microg/L prochloraz. This study serves as a
      part of the validation of the FSDT and indicates that the FSDT is suitable in
      detecting compounds with multiple endocrine actions. This is of importance in the
      assessment of the potential risk of existing and new chemicals.

PMID- 17229593
TI  - Effects of formoterol and BRL 37344 on human umbilical arteries in vitro in
      normotensive and pre-eclamptic pregnancy.
AB  - Alterations in vascular responses to beta-adrenoceptor agonists in normotensive
      pregnancy and pre-eclampsia are not fully understood. Thus, we studied changes in
      vasodilator responses to beta(2)-adrenoceptor agonist formoterol and beta(3)
      adrenoceptor agonist BRL 37344 on umbilical arteries isolated from normotensive
      (n=12) and pre-eclamptic (n=12) pregnant women. Changes in the relaxant effect of
      formoterol and BRL 37344 were investigated by measuring isometric tensions in
      endothelium-denuded strips of umbilical arteries in the presence or absence of
      metoprolol, ICI 118.551 and SR 59230A (beta(1), beta(2), beta(3)-adrenoceptor
      antagonists, respectively, 10(-6) mol/L). Effects of formoterol and BRL 37344 on
      cAMP levels of umbilical arteries were evaluated by radioimmunoassay kits.
      Formoterol (10(-10)-10(-4) mol/L) and BRL 37344 (10(-10)-10(-4) mol/L) caused
      concentration-dependent relaxation of the contraction induced by phenylephrine
      (10(-5) mol/L) in umbilical artery strips isolated from both groups. E(max)
      values of formoterol and BRL 37344 (for normotensive pregnant women: 87.33+/-0.87
      and 53.25+/-1.17 vs. for pre-eclampsia: 73.68+/-1.58 and 43.64+/-1.19, n=12,
      P>0.05, respectively) were significantly smaller in strips from pre-eclamptic
      women (P<0.05), with no significant change in pD(2) values. E(max) values of
      formoterol were significantly higher than those of BRL 37344 in both tissue
      (P<0.05). ICI 118.551 and SR 59230A, but not metoprolol, antagonized the relaxant
      effects of formoterol and of BRL 37344 on umbilical artery strips isolated from
      normotensive and pre-eclamptic pregnant women. Formoterol and BRL 37344 increased
      cAMP levels in both groups, but less significant in pre-eclamptic strips
      (P<0.05). These results suggest that the relaxation caused in human umbilical
      arteries by formoterol and BRL 37344 is mediated by a mixed population of beta(2)
      and beta(3)-adrenoceptor subtypes, with contribution of cAMP. Umbilical arteries
      from subjects with pre-eclampsia showed a weaker beta(2)- and beta(3)-receptor
      mediated relaxation to formoterol and BRL 37344, suggesting that the reduced
      action of formoterol and BRL 37344 may be partly due to a decreased effect of
      cAMP.

PMID- 17229594
TI  - Healthy endothelium: the scientific basis for cardiovascular health promotion and
      chronic disease prevention.
AB  - The vascular endothelium plays a critical role both in health and in the
      pathogenesis of chronic diseases, including cardiovascular disease. This review
      explores the underlying role of normal endothelial function in core public health
      interventions for health promotion and in the prevention and control of
      cardiovascular disease and its risk factors, as well as the application of
      endothelial science toward innovative public health programs and further
      research. Increased collaboration among basic scientists, clinician
      investigators, prevention research centers, and all public health practitioners
      is needed to facilitate the translation of the endothelial science into practice.

PMID- 17229595
TI  - Vascular endothelium summary statement II: Cardiovascular disease prevention and
      control.
AB  - The prevention and control of cardiovascular disease (CVD), principally ischemic
      heart disease and stroke, are a major clinical and public health challenge.
      Worldwide, CVD accounts for substantial morbidity and mortality. The major
      modifiable CVD risk factors are known and all of them cause endothelial
      activation and dysfunction. Preventing and controlling the established risk
      factors are associated with preserved endothelial function and reduced risk of
      CVD. Research advances that improve our understanding of strategies to preserve
      endothelial function or make the endothelial cells resilient to environmental
      insults may help improve our preventive interventions. This summary statement
      addresses the current state of the science with respect to endothelial
      dysfunction and CVD pathogenesis, diagnostic evaluation, and suggested strategies
      for public health practice and research.

PMID- 17229596
TI  - Mechanical efficacy of vertebroplasty: influence of cement type, BMD, fracture
      severity, and disc degeneration.
AB  - INTRODUCTION: Osteoporotic vertebral fractures can be treated by injecting bone
      cement into the damaged vertebral body. "Vertebroplasty" is becoming popular but
      the procedure has yet to be optimised. This study compared the ability of two
      different types of cement to restore the spine's mechanical properties following
      fracture, and it examined how the mechanical efficacy of vertebroplasty depends
      on bone mineral density (BMD), fracture severity, and disc degeneration. METHODS:
      A pair of thoracolumbar "motion-segments" (two adjacent vertebrae with
      intervening soft tissue) was obtained from each of 15 cadavers, aged 51-91 years.
      Specimens were loaded to induce vertebral fracture; then one of each pair
      underwent vertebroplasty with polymethylmethacrylate (PMMA) cement, the other
      with another composite material (Cortoss). Specimens were creep loaded for 2 h to
      allow consolidation. At each stage of the experiment, motion segment stiffness in
      bending and compression was measured, and the distribution of compressive loading
      on the vertebrae was investigated by pulling a miniature pressure transducer
      through the intervertebral disc. Pressure measurements, repeated in flexed and
      extended postures, indicated the intradiscal pressure (IDP) and neural arch
      compressive load-bearing (F(N)). BMD was measured using DXA. Fracture severity
      was quantified from height loss. RESULTS: Vertebral fracture reduced motion
      segment stiffness in bending and compression, by 31% and 43% respectively
      (p<0.001). IDP fell by 43-62%, depending on posture (p<0.001), whereas F(N)
      increased from 14% to 37% of the applied load in flexion, and from 39% to 61% in
      extension (p<0.001). Vertebroplasty partially reversed all these effects, and the
      restoration of load-sharing was usually sustained after creep-consolidation. No
      differences were observed between PMMA and Cortoss. Pooled results from 30
      specimens showed that low BMD was associated with increased fracture severity (in
      terms of height loss) and with greater changes in stiffness and load-sharing
      following fracture. Specimens with low BMD and more severe fractures also showed
      the greatest mechanical changes following vertebroplasty. CONCLUSIONS: Low
      vertebral BMD leads to greater changes in stiffness and spinal load-sharing
      following fracture. Restoration of mechanical function following vertebroplasty
      is little influenced by cement type but may be greater in people with low BMD who
      suffer more severe fractures.

PMID- 17229597
TI  - Effect of bed rest during pregnancy on bone turnover markers in pregnant and
      postpartum women.
AB  - OBJECTIVE: The aims of our study were to evaluate the changes in bone turnover
      markers during pregnancy and puerperium as a longitudinal study and to elucidate
      the effect of bed rest during pregnancy on bone turnover markers in pregnant and
      postpartum women. METHODS: The study population comprised 27 Japanese pregnant
      women aged 23-40 years. All women were recruited for the longitudinal study from
      the outpatients clinic of the Department of Obstetrics and Gynecology, Tokushima
      University Hospital. Concentrations of serum bone-specific alkaline phosphatase
      (BAP), urinary cross-linked type I collagen N-telopeptides (NTx), serum NTx and
      urinary C-terminal telopeptide of type I collagen (CTx) were measured at 10, 26,
      30 and 36 weeks of pregnancy and at 4 days and 1 month postpartum. In addition,
      we recruited 15 pregnant women (aged 25-35 years) who were treated by bed rest
      before 30 weeks of pregnancy for threatened premature delivery and compared bone
      turnover markers in these women with those in 22 normal pregnant women (aged 22
      39 years). Concentrations of serum BAP, serum NTx, urinary NTx and urinary CTx
      were measured at 30 and 34 weeks of pregnancy and at 4 days and 1 month
      postpartum. RESULTS: In the longitudinal study, serum BAP concentration at 1
      month postpartum was significantly higher than that at any stage of pregnancy and
      that at 4 days postpartum. Urinary concentration of NTx increased gradually
      during pregnancy and showed a peak at 36 weeks of pregnancy, followed by a
      decrease in the postpartum period. Serum NTx concentration and urinary CTx
      concentration showed the same patterns of change as that of urinary NTx
      concentration. In the comparison study, urinary concentrations of NTx and CTx at
      30 and 34 weeks of pregnancy in women with bed rest were significantly (p<0.0001
      and p<0.001, respectively) higher than those in normal pregnant women. Serum NTx
      concentration at 34 weeks of pregnancy in women with bed rest was also
      significantly (p=0.0029) higher than that in normal pregnant women. Serum BAP
      concentration at 34 weeks of pregnancy in women with bed rest was significantly
      (p=0.0038) higher than that in normal pregnant women, and these high levels were
      maintained during puerperium. Serum BAP concentration at 34 weeks of pregnancy
      was significantly correlated with duration of bed rest (r=0.767, p=0.0041).
      CONCLUSION: Immobilization due to bed rest during pregnancy is associated with
      increases in bone turnover markers in pregnant and postpartum women.
      Concentrations of bone resorption markers increased rapidly at the start of bed
      rest, while the concentration of a bone formation marker gradually increased
      toward puerperium.

PMID- 17229598
TI  - Guidelines for the management of actinic keratoses.

PMID- 17229599
TI  - Clinical pictures and classification of somatoform disorders in dermatology.
AB  - Somatoform disorders in dermatology are a heterogeneous group from a
      biopsychosocial point of view. Among the clinical patterns we find, for example,
      pruritus, pain, paresthesia as well as feelings of disfiguration, eco-syndromes,
      erythrophobia or psychogenic pseudoeffluvium. The multiple clinical symptoms are
      usually accompanied by psychosocial disorders, these are subjective complaints by
      the patient which cannot be medically objectified. The relevant somatoform
      disorders in dermatology can be differentiated as somatisation disorders,
      hypochondriacal disorders, somatoform autonomous disorders, persistent somatoform
      pain disorders and "other somatoform disorders". A precise differential
      diagnostic division is necessary in order to initiate adequate therapy
      strategies. With this overview article, we would like to make an updated
      classification recommendation for dermatology and present experiences in therapy.

PMID- 17229600
TI  - A glycine substitution in the COL7A1 gene causes mild RDEB in a Pakistani family.
AB  - Pathogenic glycine substitutions can cause destabilization of the triple helix
      and a diverse range of heritable connective tissue disorders, dependent on the
      collagen gene in which the mutation occurs. Mutations in the type VII collagen
      gene (COL7A1) cause an inherited mechanobullous skin disease known as dystrophic
      epidermolysis bullosa (DEB). Typically, the dominant forms (DDEB) result from
      glycine substitutions within COL7A1, whereas other glycine mutations are 'silent'
      in the heterozygous state and produce disease only when they are homozygous. We
      studied three affected individuals from a large inbred Pakistani family with a
      history of skin fragility and scarring indicative of dystrophic EB. We identified
      a new glycine substitution within the collagenous region in exon 94 of the COL7A1
      gene. This mutation, designated G2422V, resulted in a glycine (GGA) to valine
      (GTA) substitution presumably causing a destabilization of the protein by
      interrupting the Gly-X-Y repeats. This finding expands the allelic series of
      COL7A1 mutations underlying mild recessive dystrophic epidermolysis bullosa
      (RDEB) and sheds further light upon regions of the type VII collagen triple helix
      that are tolerant of heterozygous glycine substitutions.

PMID- 17229601
TI  - Epidermolysis bullosa simplex with mottled pigmentation due to de novo P25L
      mutation in keratin 5 in an Italian patient.
AB  - Epidermolysis bullosa simplex with mottled pigmentation (EBS-MP) is an autosomal
      dominant inherited disorder of the skin, which manifests as recurrent blistering,
      punctate palmo-plantar hyperkeratoses, and mottled pigmentation of the trunk and
      extremities. Previous reports have identified the P25L mutation within the non
      helical V1 domain of keratin 5 as the unique cause of the disease. We found this
      mutation in the first Italian case of EBS-MP. The proband was heterozygous for
      the P25L mutation, which occurred de novo as this change was not detected in the
      peripheral blood DNA of the healthy parents. Our report extends the limited
      number of EBS-MP cases and gives further evidence that mutation P25L is
      responsible for this unusual phenotype.

PMID- 17229602
TI  - Profiling lymphocyte subpopulations in peripheral blood under efalizumab
      treatment of psoriasis by multi epitope ligand cartography (MELC) robot
      microscopy.
AB  - CD11a-blocking efalizumab has recently been approved as a systemic treatment of
      moderate to severe chronic plaque psoriasis. When treating 6 psoriasis patients
      with efalizumab over 12 weeks in the present study, we observed an overall good
      tolerability and 5 treatment responders characterized by a decrease of PASI from
      21.3 +/- 5.4 to 3.9 +/- 0.6. The accompanying significant increase of peripheral
      blood lymphocytes from 1.9 +/- 0.7 to 4.3 +/- 1.0 x 10(9)/L (p < 0.05) was
      analyzed by multi epitope ligand cartography (MELC) robot microscopy. Thereby a
      high-dimension simultaneous multiplex immunophenotyping was pursued using 39
      fluorophore-labeled antibodies including labeled efalizumab and 3 other affinity
      reagents such as lectins. Due to efalizumab treatment there was a substantial
      decrease of the cellular expression of CD11a (detected by mab clone 25.3.1) and
      efalizumab binding sites (EfaBSs). This was paralleled by an increase of the
      number of EfaBS- and EfaBS+ lymphocytes by a factor of 2.4x and 2.2x,
      respectively. The latter effect was mainly derived from a subpopulation showing a
      low degree of EfaBS expression. Efalizumab treatment led furthermore to an
      increase of the numbers of CD3+, CD4+, CD8+, CD44+, CD45+, CD45R0+, CD45 RA+,
      CD52+, CD58+, CD247+, HLA-DR+ and Sambucus nigra lectin-reactive lymphocytes (by
      factors from 2.0 to 3.3x). In terms of a combinatorial molecular phenotype we
      identified a CD3+/CD4+/CD44+/CD52+ lymphocyte subpopulation which accumulated
      most predominantly from 0.824 +/- 0.270 x 10(9)/L up to 1.616 +/- 0.152 x 10(9)/L
      under efalizumab treatment (p < 0.01). Thus, the current study extends the
      knowledge of efalizumab-dependent perturbations of recirculating blood lymphocyte
      subpopulations in psoriasis patients.

PMID- 17229603
TI  - Toll-like receptors 2, 4 and 9 expression in cutaneous T-cell lymphoma (mycosis
      fungoides and Sezary syndrome).
AB  - The aim of this work was to study Toll-like receptors (TLRs) 2, 4 and 9
      expression patterns in parapsoriasis and in cutaneous T-cell lymphoma (CTCL):
      Mycosis fungoides (MF) and Sezary syndrome (SS) at different stages of the
      illness. The expression of TLRs was examined by immunohistochemistry on paraffin
      embedded biopsies. Normal skin, atopic dermatitis and psoriasis, were used as
      controls. In cutaneous lesions of inflammatory diseases (atopic dermatitis,
      psoriasis) the expression of TLR2, TLR4 and TLR9 was low compared to normal skin.
      In parapsoriasis the expression of the three TLRs was similar to control. By
      contrast, in MF skin we observed a strong intensity of labelling with the three
      TLRs in the epidermis. Concerning SS, the expression of TLR2, TLR4 and TLR9 was
      intermediate between inflammatory lesions and MF. Thus, the development of skin
      lesions in MF appears associated with an increase of TLR2, TLR4 and TLR9
      expression by keratinocytes in cutaneous lesions, which could play a role in the
      chronic activation of T lymphocytes in the skin.

PMID- 17229604
TI  - Randomized, comparative trial on the sustained efficacy of topical imiquimod 5%
      cream versus conventional ablative methods in external anogenital warts.
AB  - Conventional ablative treatments for external anogenital warts are affected by
      high recurrence rates. This study compared sustained clearance after ablation vs.
      treatment with imiquimod 5% cream vs. the combination of both methods. This was a
      3-arm, open-label, randomized clinical study comparing ablation alone (Group A),
      imiquimod 5% cream monotherapy (Group B), or combined ablation followed by
      topical imiquimod (Group C). Subjects whose anogenital warts were completely
      cleared entered a 6-month follow-up to evaluate sustained clearance. After 3
      months follow-up, 83.9% (73/87), 93.8% (90/96) and 91.7% (66/72) of subjects in
      Groups A, B, C, respectively, remained free of recurrent anogenital warts. After
      6-months follow-up, 73.6% (64/87), 93.7% (89/95) and 91.5% (65/71) of subjects
      presented free of recurrence (Group A vs. B & C p-values each p < 0.004 in favour
      of the imiquimod-treated groups). Imiquimod 5% cream, as monotherapy or in
      combination with ablation, was superior to ablation alone in reducing the
      recurrence of successfully treated anogenital warts.

PMID- 17229605
TI  - Emedastine difumarate versus loratadine in chronic idiopathic urticaria: a
      randomized, double-blind, controlled European multicentre clinical trial.
AB  - Emedastine difumarate (2 mg b.i.d.) was compared to loratadine (10 mg o.d.) in a
      randomized, double-blind, multicentre trial for 4 weeks in 192 patients with
      idiopathic chronic urticaria. After one week of treatment significant differences
      were recorded: body skin involvement diminished to 0-10% in 57.1% of emedastine
      patients vs. 38.2% of loratadine patients (p = 0.0019) and 83.3% had a total
      urticaria symptom score of 0-1 vs. 64.5% with loratadine (p = 0.0134). After 4
      weeks of treatment the efficacy of the two drugs was similar in terms of mean
      change in total urticaria symptom score (- 5.57 +/- 3.15 with emedastine - 5.67
      +/- 3.26 with loratadine), proportion of symptom-free patients (52.4% vs. 54.5%),
      intensity of erythema, number of hives, size of the largest hive, extent of skin
      area involved and overall assessment of urticaria symptoms.Twenty-three
      emedastine patients (23.9%) and 17 loratadine patients (17.7%) experienced an
      adverse event. Nineteen events in 15 emedastine patients and 9 in 9 loratadine
      patients were related to treatment (p = 0.0294). Only one event caused
      discontinuation in both treatment groups. The most common adverse event was
      sleepiness (7 patients with emedastine and 2 with loratadine). Emedastine is well
      tolerated, and as effective as loratadine in the short-term treatment of chronic
      idiopathic urticaria.

PMID- 17229606
TI  - Xenovaccinotherapy for melanoma.
AB  - The objectives of this phase I-II trial were to assess the toxicity,
      immunological and clinical responses induced in stage III/IV melanoma patients by
      the subcutaneous administration of xenogenic polyantigenic vaccine (XPV) prepared
      from disrupted murine melanoma (B16) and carcinoma (LLC) cells. An inducing
      course of vaccinotherapy consisted of ten immunizations (five at weekly and five
      at fortnight intervals). Twenty-four hours following each of the first five
      vaccinations, the patient was subcutaneously given a low dose of the recombinant
      interleukin-2 (IL-2). A consolidating course of the vaccinotherapy consisted of
      monthly vaccinations. Grade 3 or 4 toxicities, as well as laboratory and clinical
      signs of developing autoimmune disorders, were recorded in none of the 40 XPV
      treated evaluable patients. A significant increase in delayed-type
      hypersensitivity (DTH) skin reaction to vaccinal B16, but not to LLC antigens
      (Ags), occurred in patients after inducing vaccinations. At the same time, those
      patients demonstrated a marked augmentation of blood lymphocyte proliferation
      responses not only to B16 but also to LLC Ags. Vaccinations also led to increased
      cell-mediated reactivity to murine non-tumor, spleen cell (SC)-associated Ags,
      which, however, was not as significant as that to tumor-associated antigens
      (TAAs). Of great importance was the fact that XPV administration resulted in
      increased blood lymphocyte proliferative reactivity of patients to human melanoma
      associated Ags, while not affecting their reactivity to the control alloantigens.
      With immunotherapy, concentrations of both interferon-gamma (IFN-gamma) and
      interleukin-4 (IL-4) were elevated in patients' sera, suggesting an
      intensification of the T helper1/ T helper 2-mediated responses in the XPV
      treated patients. The average survival of the 32 stage IV melanoma XPV-treated
      evaluable patients was noticeably higher than that of the 32 clinically
      comparable control patients (13 vs. 5 months). The overall 3 year-survival rate
      in the XPV-treated group and the control group was 25% (8 patients) and 3% (1
      patient), respectively. In general, the results suggest that xenogenic tumor
      cells may provide a novel feasible approach to constructing clinically effective
      vaccines.

PMID- 17229607
TI  - Prevalence of sexually transmitted infections in female sex workers in Athens,
      Greece - 2005.
AB  - There is little data on the prevalence of STIs in female sex workers, Greek and
      immigrants, working in Athens, Greece, since most of them work without any form
      of official license. Our aim was to establish the prevalence of STIs in
      asymptomatic legal Greek and immigrant female sex workers in Athens, Greece. The
      study involved an evaluation of gonococcal and chlamydial infection, early
      infectious syphilis, HIV infection, HSV-2 infection, Hepatitis B and C in 299
      female sex workers who applied for an official work permit between May 2005 and
      October 2005. HSV-2 infection was more common in the Greek sex workers. No
      difference was found for the other STIs. Prevalence was related to age. A
      significant association was found between HSV-2 and syphilis. No HIV infection
      was detected. We concluded that asymptomatic sex workers can be a source of STIs
      which points out the need for a better health system control in Greece.

PMID- 17229608
TI  - Association of hypogammaglobulinemia with DRESS (Drug Rash with Eosinophilia and
      Systemic Symptoms).
AB  - The association of hypogammaglobulinemia was recently reported in anticonvulsant
      associated DRESS. Hypogammaglobulinemia could be the consequence of
      hypoproteinemia in patients with erythroderma. To ascertain the association of
      hypogammaglobulinemia with DRESS we compared the prevalence of
      hypogammaglobulinemia in DRESS and in other cause of erythroderma. In a
      retrospective study, 39 consecutive patients with DRESS were compared to 52
      patients with other causes of erythroderma hospitalized in the same period.
      Hypogammaglobulinemia was statistically significantly associated with DRESS (p =
      0.022). This association was not limited to anticonvulsants (phenytoin,
      carbamazepin) and was observed with other drugs (allopurinol, tazocillin,
      ibuprofen, celecoxib, vancomycin).

PMID- 17229609
TI  - Generalized pustular psoriasis (Zumbusch): a French epidemiological survey.
AB  - A retrospective epidemiological survey of generalized pustular psoriasis (GPP)
      was carried out in France in 2005. 121 dermatological wards received a
      questionnaire concerning the patients treated in 2004. It related to demographic
      data, morbidity, mortality, failures and the therapeutic practices of each ward.
      CNAMTS, the main French health insurance, was also questioned about its registry
      concerning GPP.112 wards (92.5%) answered the questionnaire, totalling 99 cases
      (sex ratio male/female: 0.77, mean age 52.5 years +/- 18), which were handled by
      46 wards. Incidence and prevalence were estimated in 2004 at a minimum of 0.64
      and 1.76/million respectively. Incidence deduced from the CNAMTS data in 1998 and
      2001 was similar. The treatment habits were the same in the 46 wards, which used
      acitretin as first line treatment (89%), followed by methotrexate (8%). High
      potency dermatocorticosteroids (DC) were most often used (87%). Complications and
      death were noted in 17% and 2% of the cases respectively, recalcitrant GPP in
      42%. Immunobiologics were required in 13% of patients. Univariate analysis showed
      that treatment failure was related to: i) management in a university ward (OR:
      2.9, p = 0.03) probably reflecting the management of the more severe cases ii)
      prescription of high or very high potency DC as first line local therapy (OR:
      7.6, p = 0.05) iii) therapies other than retinoids as first line systemic therapy
      (OR: 5.5, p = 0.04). The systemic treatment is well codified but future studies
      will have to confirm the usefulness of DC in the management of GPP.

PMID- 17229610
TI  - Oral mucosa manifestations in 100 pregnant versus non-pregnant patients: an
      epidemiological observational study.
AB  - The effect of pregnancy on the oral mucosa is not clear. A study was designed to
      contrast the number and the type of oral mucosa lesions present in pregnant
      (study group) and non-pregnant women (control group). A total of 200 women, of
      whom 100 were pregnant and 100 non-pregnant controls with similar age
      distribution were chosen at random from obstetrics and dermatology departments,
      Fatih University Hospital. Oral mucosa lesions were documented in both groups.
      The data were presented as percentages and comparisons were made based on the chi
      square test. The frequency of oral mucosa lesions was greater among the pregnant
      women than in control group (71.0% versus 29.0%). Cheek biting and oral
      candidiasis were seen more frequently in pregnant women than the control group.
      Pregnant women with cheek biting presented in 31 patients (31%) and in control 5
      (5%) which was statistically significant, p < 0.001. Oral candidiasis presented
      in 15 (15%) pregnant versus 5 (5%) in control, which was also statistically
      significant, p = 0.018. Pregnant women with vomiting were more frequently seen
      with oral mucosa lesions than pregnant women without vomiting (35 (77.8%) versus
      27 (49.1%)), which was statistically significant (p = 0. 003). We concluded that
      cheek biting and oral candidiasis were the oral mucosa lesions with the greatest
      prevelances during pregnancy. Pregnant women who visit dermatology clinics should
      be routinely examined for oral mucosa lesions.

PMID- 17229611
TI  - HIV - associated and non - HIV associated types of Kaposi's sarcoma in an African
      population in Tanzania. Status of immune suppression and HHV-8 seroprevalence.
AB  - In this study 77 patients with histologically confirmed Kaposi's sarcoma (KS)
      were seen at the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania.
      Sixty six patients (85.7%) were HIV-seropositive KS-patients (40 males, 26
      females; male: female ratio 1.5:1), whereas another 11 (14.3%) KS-patients, all
      males, were found HIV-seronegative, thus corresponding to the endemic African KS
      type. In both groups the CD4+ cell counts were generally low, the CD8+ population
      increased and the CD4+/CD8+ ratio inverted. Immune suppression was, however, more
      prominent in the HIV-seropositive group.HHV-8 seroprevalence was high in patients
      with HIV-associated KS (94.6%), nevertheless, 3 (5.4%) patients in this group
      remained HHV-8 seronegative. All nine patients with the HIV-seronegative African
      type of KS were found positive for HHV-8. Of the entire group seen, males were
      more likely to be HHV-8 seropositive than females (OR = 3.348 95% CI, 0.96-11.65;
      p < 0.05). The relative risk to develop KS in individuals seropositive to both
      HIV and HHV-8 was high (OR = 10.6, 95% CI; 2.981-37.688; p < 0.001).Overall, HIV
      associated KS differed from the non-HIV-associated by its widespread clinical
      dissemination on the trunk, the frequent involvement of the oral mucosa and the
      craniofacial region, and its more rapidly progressive course. No histological
      differences between the two KS-groups were seen, although spindle cell
      infiltrates were more often found in the HIV-associated KS-group.

PMID- 17229612
TI  - Infantile erythema elevatum diutinum: report of a vesiculo-bullous case.
AB  - Erythema elevatum diutinum (EED) is a localized, low-grade form of
      leukocytoclastic vasculitis mainly affecting adults, with only a few pediatric
      cases reported in the literature. The pathogenesis of this dermatosis is unknown,
      although an Arthus-type reaction to bacterial and viral antigens seems involved.
      We describe a case of EED in a 9 year-old child suffering from recurrent
      pharyngotonsillitis induced by Streptococcus pyogenes. Clinical presentation of
      the dermatosis was atypical, with vesicles and bullae intermingled with red
      purple papules and plaques distributed mainly over the extensor aspects of the
      extremities. Histopathological examination of a vesiculo-bullous lesion revealed
      a subepidermal bulla containing neutrophils and nuclear dust suggesting
      dermatitis herpetiformis. Fibrin in vessel walls was observed throughout the
      dermis. Direct immunofluorescence was negative. A prompt and complete response to
      sulphone therapy was obtained in conjunction with tonsillectomy. Clinicians
      should be aware of atypical presentations of EED in children with vesicles and
      bullae mimicking During's disease.

PMID- 17229613
TI  - Subcorneal pustulosis and Pyoderma gangrenosum associated with a biclonal
      gammopathy.
AB  - Pyoderma gangrenosum and subcorneal pustulosis are two neutrophilic dermatoses.
      Their occurrence in the same patient is rare and may be related to an IgA
      dysglobulinemia. We report a case presenting these two conditions associated with
      a biclonal benign IgA and IgG gammopathy. A 67-year-old man exhibited typical
      pyoderma gangrenosum associated after three years duration with subcorneal
      pustulosis lesions, confirmed by cutaneous biopsy. Laboratory results showed a
      biclonal benign IgA and IgG kappa gammopathy. Therapeutic management was
      difficult: Pyoderma gangrenosum responded well to corticosteroids but subcorneal
      pustulosis management was harder and treatments were poorly effective.Pyoderma
      gangrenosum and subcorneal pustulosis are a part of the neutrophilic spectrum.
      Their association has been only reported in eleven patients. In eight cases, an
      IgA dysglobulinemia was associated suggesting its responsibility in the
      occurrence of both dermatoses. Treatments are various and not fully effective. If
      the Pyoderma gangrenosum usually responds to corticosteroids, the subcorneal
      pustulosis treatments are not well defined and often not efficient. Our case
      illustrates the dissociated evolution of these two dermatoses and their difficult
      global management. During the follow-up, a regular search for dysglobulinemia is
      required in order to detect malignant transformations.

PMID- 17229614
TI  - Metastatic basal cell carcinoma: is infiltrative/morpheaform subtype a risk
      factor?

PMID- 17229615
TI  - Linear IGA dermatosis associated with ulcerative colitis.

PMID- 17229616
TI  - Paclitaxel-induced nail changes: possible role of its vehicle (Cremophor EL).

PMID- 17229617
TI  - Generalized eruptive histiocytoma: a pediatric case.

PMID- 17229618
TI  - Half-and-half nail in a case of pellagra.

PMID- 17229619
TI  - Reactive perforating collagenosis with cutaneous cytomegalovirus infection.

PMID- 17229620
TI  - Nevus comedonicus syndrome in a woman with Paget bone disease and breast cancer:
      a mere coincidence?

PMID- 17229621
TI  - Paraneoplastic pemphigus with pemphigus vegetans-like lesions revealing non
      Hodgkin lymphoma.

PMID- 17229622
TI  - Toxic epidermal necrolysis due to omeprazole.

PMID- 17229623
TI  - Lichen sclerosus et atrophicus-like chronic graft-versus-host disease.

PMID- 17229624
TI  - Azithromycin is not effective in the treatment of old world cutaneous
      leishmaniasis.

PMID- 17229625
TI  - Treatment of Gottron papules of dermatomyositis with pulsed dye laser.

PMID- 17229626
TI  - Unilateral erythema nodosum-like lesions and superficial thrombophlebitis
      together with ipsilateral thrombosis of the vena femoralis in Behcet's disease.

PMID- 17229628
TI  - Treatment of acquired aplastic anemia.

PMID- 17229629
TI  - Treatment of refractory and relapsed Hodgkin's lymphoma: facts and perspectives.

PMID- 17229630
TI  - Outcome of patients with acquired aplastic anemia given first line bone marrow
      transplantation or immunosuppressive treatment in the last decade: a report from
      the European Group for Blood and Marrow Transplantation (EBMT).
AB  - BACKGROUND AND OBJECTIVES: The treatment of acquired aplastic anemia (AA) is
      based on allogeneic bone marrow transplantation (BMT) and immunosuppressive
      therapy. The aim of this study was to assess the outcome of children and adults
      with AA treated in the last decade, and to determine whether results have
      improved in two sequential time periods,1991-1996 and 1997-2002. DESIGN AND
      METHODS: Two-thousands and seventy-nine consecutive patients with AA, classified
      according to first-line treatment: BMT (n=1567) or immunosuppressive therapy (n=
      912), the patients for the two sequential time periods were studied. Analyses
      included variables related to patients, disease and transplant. RESULTS: The
      actuarial 10-year survival was 73% and 68% for BMT or immunosuppressive
      treatment, respectively (p=0.002). BMT outcome improved significantly with time
      (69% and 77%, p=001) for both matched sibling donor (MSD) (74% and 80%; p=0.003
      ), alternative donor (38% and 65% p=0.0001), and was better in children (79%
      versus 68%, p<0.0001). Multivariate analysis: favorable predictors (p<0.001) were
      younger age, transplant beyond 1996, MSD, a short interval diagnosis-transplant ,
      no irradiation. IS: no significant improvement over time (69% and 73% p=0.29).
      Survival was significantly better in children (81% versus 70%, p=0.001),
      especially in vSAA(83% versus 62%, p=0.0002). Combined IS was superior to single
      drug treatment (77% versus 62%, p=0.002). Multivariate analysis: significant
      predictors of survival: age > or =16 years (p=0.0009), longer interval between
      diagnosis -treatment (p=0.04), single drug versus combined IS (p=0.02).
      INTERPRETATION AND CONCLUSIONS: Outcome has improved in subsets of AA patients:
      those receiving first- line BMT and children with vSAA treated with IS. Age
      remains a major predictor for both treatments. Early intervention is associated
      with a significantly better outcome and is strongly recommended, whatever the
      first-line therapy.

PMID- 17229631
TI  - Anti-erythroblast autoimmunity in early myelodysplastic syndromes.
AB  - BACKGROUND AND OBJECTIVES: Autoimmune phenomena, mainly directed against red
      blood cells are described in myelodysplastic syndromes (MDS), particularly early
      MDS, i.e. refractory anemia (RA) and RA with ringed sideroblasts (RARS).
      Dysregulation of apoptosis and immunoregulatory cytokines are thought to play a
      role in the pathogenesis of MDS. DESIGN AND METHODS: This work was aimed to
      investigate anti-erythroid autoimmunity in unstimulated and mitogen-stimulated
      peripheral blood and bone marrow cultures of 26 patients with early MDS (RA and
      RARS), and to relate its presence with apoptotic markers and cytokine production.
      Bone marrow cytokine production in culture supernatants, and caspase-3 and
      nuclear factor-kappaB activity in cell extracts were tested by enzyme-linked
      immunosorbent assays. RESULTS: Fourteen of the 26 (53.8%) patients showed the
      presence of autoantibodies in bone marrow cultures, whereas none displayed a
      positive direct antiglobulin test in peripheral blood cultures. Incubation of
      culture supernatants from positive patients with autologous CD45- enriched-cell
      suspensions showed that the autoimmune reaction was directed against autologous
      erythroblasts. These patients had mild signs of hemolysis and increased numbers
      of erythroblasts, compared with negative patients. Patients with anti
      erythroblast autoimmunity displayed higher caspase-3 activity and lower tumor
      necrosis factor-alpha and interleukin-4 production than did negative patients.
      INTERPRETATION AND CONCLUSIONS: Half of the patients with early MDS showed
      autoimmunity against erythroblasts. This evidence might support a more rationale
      use of steroid therapy in these patients. The lower levels of cytokines in
      patients with anti-erythroblast autoimmunity are consistent with the suggested
      hypothesis that the autoimmune phenomena observed in MDS are probably initiated
      and perpetuated through alterations of pro-inflammatory and/or immunoregulatory
      cytokine production.

PMID- 17229632
TI  - The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and
      overcome resistance to other small molecule inhibitors.
AB  - BACKGROUND AND OBJECTIVES: Activated tyrosine kinases are implicated in the
      pathogenesis of chronic and acute leukemia, and represent attractive targets for
      therapy. Sorafenib (BAY43-9006, Nexavar) is a small molecule B-RAF inhibitor that
      is used for the treatment of renal cell carcinoma, and has been shown to have
      activity against receptor tyrosine kinases from the platelet-derived growth
      factor receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR)
      families. We investigated the efficacy of sorafenib at inhibiting mutants of the
      receptor tyrosine kinases PDGFRbeta, KIT, and FLT3, which are implicated in the
      pathogenesis of myeloid malignancies. DESIGN AND METHODS: We tested the effect of
      sorafenib on the proliferation of hematopoietic cells transformed by ETV6
      PDGFRbeta, FLT3 with an internal tandem duplication or D835Y point mutation, and
      the KIT(D816V) mutant. The direct effect of sorafenib on the activity of these
      kinases and their downstream signaling was tested using phospho-specific
      antibodies. RESULTS: We show that sorafenib is a potent inhibitor of ETV6
      PDGFRbeta and FLT3 mutants, including some of the mutants that confer resistance
      to PKC412 and other FLT3 inhibitors. Sorafenib induced a cell cycle block and
      apoptosis in the acute myeloid leukemia cell lines MV4-11 and MOLM-13, both
      expressing FLT3 with an internal tandem duplication, whereas no effect was
      observed on four other acute myeloid leukemia cell lines. The imatinib-resistant
      KIT(D816V) mutant, associated with systemic mastocytosis, was found to be
      resistant to sorafenib. INTERPRETATION AND CONCLUSIONS: These results warrant
      further clinical studies of sorafenib for the treatment of myeloid malignancies
      expressing activated forms of PDGFRbeta and FLT3.

PMID- 17229633
TI  - Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory
      and relapsed Hodgkin's lymphoma.
AB  - BACKGROUND AND OBJECTIVES: Response to pre-transplant salvage chemotherapy
      remains the most important prognostic factor for outcome in refractory or
      relapsed Hodgkin's lymphoma. Results of a new induction regimen are reported in
      terms of response rates, toxicity, and stem cell mobilization. DESIGN AND
      METHODS: Ninety-one patients with refractory or relapsed Hodgkin's lymphoma were
      treated prospectively with a salvage regimen consisting of ifosfamide 2000 mg/m2
      on days 1 to 4, gemcitabine 800 mg/m2 on days 1 and 4, vinorelbine 20 mg/m2 on
      day 1, and prednisolone 100 mg on days 1 to 4 (IGEV). RESULTS: Forty-nine
      patients (53.8%) achieved a complete remission and 25 (27.5%) a partial response
      for an overall response rate of 81.3%. In the multivariate analysis response to
      the last chemotherapy (p<0.0001) and involvement of > or =3 sites (p<0.049) were
      the most important prognostic factors for response. Adequate CD34+ cell
      collection was achieved in 78 out of 79 (98.7%) mobilized patients. So far, no
      treatment-related death has been documented. Thirteen (4.2%) and 27 (8.6%) out of
      313 evaluated cycles had to be delayed or reduced, respectively, mainly because
      of neutropenia and thrombocytopenia. No grade 4 non-hematologic toxicity was
      observed, except for one episode of mucositis. INTERPRETATION AND CONCLUSIONS:
      The high response rate, in particular the complete remission rate, the low
      toxicity profile, and the very high mobilizing potential of the IGEV regimen
      strongly suggest that patients with relapsed/refractory Hodgkin's lymphoma may
      benefit from the use of this salvage induction regimen.

PMID- 17229634
TI  - Rituximab-augmented myeloablation for first-line autologous stem cell
      transplantation for mantle cell lymphoma: effects on molecular response and
      clinical outcome.
AB  - BACKGROUND AND OBJECTIVES: Autologous stem cell transplantation (ASCT) is
      effective in mantle cell lymphoma (MCL). We investigated whether incorporation of
      rituximab into the high-dose regimen might further improve the results of ASCT in
      patients with MCL. DESIGN AND METHODS: In a prospective phase II study, patients
      with newly diagnosed MCL were treated with a sequential dose-escalating therapy
      comprising standard chemotherapy for remission induction, intensive ara-C
      containing chemotherapy for mobilization of stem cells, and myeloablative therapy
      followed by ASCT. The myeloablative regimen consisted of total body irradiation
      and high-dose cyclophosphamide supplemented with two doses (375 mg/m3) of
      rituximab. Outcome parameters (toxicity, clinical and molecular response as
      assessed by allele-specific IGH real-time quantitative polymerase chain reaction
      (RQ-PCR), event-free survival, and overall survival) were compared with those of
      34 historical controls treated identically but without rituximab. RESULTS: Thirty
      four patients were accrued. Whereas engraftment, toxicity and clinical response
      were not different from those in controls, event-free survival was significantly
      increased with rituximab (not reached vs. 43 months; hazard ratio 0.38; p=0.036).
      This was associated with a trend for a superior molecular response rate in 11
      study vs. 10 control patients with a marker available (73% vs. 30%, p=0.086)
      despite similar levels of lymphoma contamination of the stem cell inocula
      infused. INTERPRETATION AND CONCLUSIONS: Incorporation of two standard doses of
      rituximab into the myeloablative regimen might improve outcome of up front ASCT
      for MCL, allowing long-term disease control to an extent previously not reached
      in this disease.

PMID- 17229635
TI  - A prospective comparison of 18F-fluorodeoxyglucose positron emission tomography
      computed tomography, magnetic resonance imaging and whole-body planar radiographs
      in the assessment of bone disease in newly diagnosed multiple myeloma.
AB  - BACKGROUND AND OBJECTIVES: Bone lesions in multiple myeloma (MM) have been
      traditionally detected by whole body X-ray (WBXR) survey although magnetic
      resonance imaging (MRI) has become the gold standard for detecting MM involvement
      of the spine and pelvis. The aim of this study was to compare a new technique,
      positron emission tomography (PET) with 18F fluorodeoxyglucose (FDG) integrated
      with computed tomography (18F-FDG PET-CT), with MRI and WBXR for baseline
      assessment of bone disease in MM. DESIGN AND METHODS: We prospectively compared
      18F-FDG PET-CT, MRI of the spine-pelvis and WBXR in a series of 46 patients with
      newly diagnosed MM. In 23 patients who received up front autologous
      transplantation, we also compared post-treatment PET-CT scans with MR images of
      the spine and pelvis. RESULTS: Overall, PET-CT was superior to planar radiographs
      in 46% of patients, including 19% with negative WBXR. In 30% of patients, PET-CT
      scans of the spine and pelvis failed to show abnormal findings in areas in which
      MRI revealed an abnormal pattern of bone marrow involvement, more frequently of
      diffuse type. In contrast, in 35% of patients PET-CT enabled the detection of
      myelomatous lesions in areas which were out of the field of view of MRI. By
      combining MRI of the spine- pelvis and 18F-FDG PET-CT, the ability to detect
      sites of active MM, both medullary and extramedullary, was as high as 92%.
      Following transplantation, 15 patients had negative PET-CT scans (including 13
      with a very good partial response or at least a near complete response), but only
      8 had normal MRI. INTERPRETATION AND CONCLUSIONS: MRI of the spine and pelvis
      still remains the gold standard imaging technique for the detection of bone
      marrow involvement in MM. 18F-FDG PET-CT provides additional and valuable
      information for the assessment of myeloma bone disease in areas not covered by
      MRI.

PMID- 17229636
TI  - Integrative genomic analysis reveals distinct transcriptional and genetic
      features associated with chromosome 13 deletion in multiple myeloma.
AB  - BACKGROUND AND OBJECTIVES: The chromosome 13 deletion (Delta13) is one of the
      most frequent chromosomal alterations in multiple myeloma (MM). Delta13 is
      associated with an unfavorable prognosis, although there is increasing agreement
      that its prognostic relevance must be related to the ploidy status and the
      presence of different chromosomal translocations. The aim of this study was to
      provide a comprehensive analysis of the transcriptional features of Delta13 in
      MM. DESIGN AND METHODS: Highly purified plasma cells from 80 newly diagnosed MM
      patients were characterized by means of fluorescence in situ hybridization (FISH)
      and high-density oligonucleotide microarray for gene expression profiling and
      chromosomal alterations. RESULTS: We identified 67 differentially expressed genes
      in the patients with and without the chromosome 13 deletion, all of which were
      downregulated in the cases with Delta13: 44 mapped along the whole chromosome 13,
      seven on chromosome 11 and three on chromosome 19. Functional analyses of the
      selected genes indicated their involvement in protein biosynthesis,
      ubiquitination and transcriptional regulation. An integrative genomic approach
      based on regional analyses of the gene expression data identified distinct
      chromosomal regions whose global expression modulation could differentiate
      Delta13-positive cases, in particular the upregulation of 1q21-1q42 and the
      downregulation of 19p and almost the entire chromosome 11. FISH analyses
      confirmed the close relationship between Delta13-positivity and the presence of
      extra copies of 1q21-1q42 (p=6 x 10(-4)) or the absence of chromosome 11 and 19
      trisomy (p=5 x 10(-4)). INTERPRETATION AND CONCLUSIONS: Our results indicate that
      distinct types of chromosomal aberrations are closely related to the
      transcriptional profiles of Delta13-positive cases, suggesting that the
      contribution of Delta13 to the malignancy should be considered together with
      associated abnormalities.

PMID- 17229637
TI  - Rituximab for the treatment of acquired antibodies to factor VIII.
AB  - BACKGROUND AND OBJECTIVES: Rituximab, a monoclonal chimeric antibody to the CD20
      antigen, is an effective therapy for the treatment of non-Hodgkin's lymphomas.
      Moreover, rituximab has also shown to be effective in various autoimmune diseases
      including spontaneous antibodies to factor VIII. The aim of this study was to
      assess the efficacy of rituximab treatment of spontaneous inhibitors to factor
      VIII. DESIGN AND METHODS: We studied the efficacy of rituximab by analyzing the
      data of 42 previously published cases as well as one so far unpublished case. For
      comparison, we also analyzed 44 patients treated with cyclophosphamide/prednisone
      reported in the literature. RESULTS: Treatment with rituximab resulted in an
      overall rate of complete remission (CR) of 78.6%. Similar results were found when
      analyzing patients who had (75%) or had not (77%) received previous treatment
      with other immunosuppressive drugs. The median time to CR was 8.3 weeks. In
      follow-up 66% of the patients were still in CR after 2 years and the plateau in
      the Kaplan-Meier analysis suggests that a substantial number of patients had been
      cured. Among the 44 patients treated with cyclophosphamide/prednisone reported in
      the literature, the CR-rate was 84.1%, which was slightly higher than that for
      rituximab. The median time to CR with cyclophosphamide/prednisone treatment was
      6.3 weeks, which was similar to that in the rituximab-treated patients; the
      probability of continuous CR at 2 years was 94%. INTERPRETATION AND CONCLUSIONS:
      All in all, both treatment schemes are effective therapies in patients with
      spontaneous antibodies to factor VIII. Our data analysis is only descriptive and
      no conclusions can be drawn as to the relative efficacy of the two regimens.
      However, these data may serve as a useful basis for planning randomized studies
      to definitively resolve these issues.

PMID- 17229638
TI  - Phase I/II feasibility study evaluating the generation of leukemia-reactive
      cytotoxic T lymphocyte lines for treatment of patients with relapsed leukemia
      after allogeneic stem cell transplantation.
AB  - BACKGROUND AND OBJECTIVES: Graft-versus-host-disease may be avoided and the
      likelihood of a graft-versus-leukemia reaction increased by infusion of in vitro
      generated, leukemia-reactive, cytotoxic T lymphocyte (CTL) lines as treatment for
      patients with relapsed leukemia after allogeneic stem cell transplantation,
      instead of donor lymphocyte infusion. The aim of this study phase I/II study was
      to assess the feasibility of large-scale in vitro generation of leukemia-reactive
      CTL for clinical use. DESIGN AND METHODS: Using a modified limiting dilution
      culture system donor T cells were stimulated with HLA-identical leukemic antigen
      presenting cells. Feasibility experiments demonstrated that in 16 of 27 donor
      recipient pairs tested a CTL line could be generated. Twelve of these 16 patients
      developed a relapse and for 11 of these 12 patients a CTL line was generated
      under Good Manufacturing Practice conditions. RESULTS: The CTL lines showed
      moderate to high cytotoxic activity against original recipient leukemic cells in
      vitro. Eight patients with a relapse received from one to seven CTL lines. One
      patient entered a complete remission after CTL infusion only, one entered a
      complete remission after combined CTL infusion and donor lymphocyte infusion, two
      patients had temporarily stable disease, and in four patients no response was
      observed. INTERPRETATION AND CONCLUSIONS: Although the current procedure to
      generate these CTL lines is feasible, the strategy is logistically complex and
      time-consuming, and needs further improvement. Key words: cellular immunotherapy,
      CTL, leukemia, allogeneic stem cell transplantation.

PMID- 17229639
TI  - Deregulation of apoptosis in acute myeloid leukemia.
AB  - Apoptosis, or programmed cell death, is central to the development and
      homeostasis of the hematopoietic system. Dysregulation of apoptosis plays an
      important role in the development of a variety of human pathologies, including
      cancer, autoimmune diseases and neurodegenerative disorders. Particularly,
      studies carried out in the last years have shown that leukemia cells invariably
      have abnormalities in one or more apoptotic pathways, determining a survival
      advantage of these cells over their normal counterpart. Furthermore,
      abnormalities in the apoptotic response also play a role in the development of
      drug resistance by leukemic cells. The identification of the different components
      of the apoptotic pathways has enabled the detection of various biochemical
      defects present in leukemic cells compared to their normal counterpart. These
      defects contribute to the survival advantage of the leukemic clone over the
      normal hematopoietic cells and are also frequently associated with a low rate of
      response to standard chemotherapy treatment and with poor survival. Furthermore,
      these findings have also lead to the identification of many potential apoptotic
      targets for the development of new drugs targeting anti-apoptotic molecules
      abnormally expressed or regulated in leukemic cells. Many of these drugs restore
      the sensitivity of leukemic cells to apoptotic stimuli and some of them are under
      investigation at a clinical level.

PMID- 17229640
TI  - Diagnostic criteria for hematopoietic stem cell transplant-associated
      microangiopathy: results of a consensus process by an International Working
      Group.
AB  - BACKGROUND AND OBJECTIVES: There are no widely accepted criteria for the
      definition of hematopoietic stem cell transplant -associated microangiopathy
      (TAM). An International Working Group was formed to develop a consensus
      formulation of criteria for diagnosing clinically significant TAM. DESIGN AND
      METHODS: The participants proposed a list of candidate criteria, selected those
      considered necessary, and ranked those considered optional to identify a core set
      of criteria. Three obligatory criteria and four optional criteria that ranked
      highest formed a core set. In an appropriateness panel process, the participants
      scored the diagnosis of 16 patient profiles as appropriate or not appropriate for
      TAM. Using the experts' ratings on the patient profiles as a gold standard, the
      sensitivity and specificity of 24 candidate definitions of the disorder developed
      from the core set of criteria were evaluated. A nominal group technique was used
      to facilitate consensus formation. The definition of TAM with the highest score
      formed the final PROPOSAL:  RESULTS: The Working Group proposes that the
      diagnosis of TAM requires fulfilment of all of the following criteria: (i) >4%
      schistocytes in blood; (ii) de novo, prolonged or progressive thrombocytopenia
      (platelet count <50 x 109/L or 50% or greater reduction from previous counts);
      (iii) sudden and persistent increase in lactate dehydrogenase concentration; (iv)
      decrease in hemoglobin concentration or increased transfusion requirement; and
      (v) decrease in serum haptoglobin. The sensitivity and specificity of this
      definition exceed 80%. INTERPRETATION AND CONCLUSIONS: The Working Group
      recommends that the presented criteria of TAM be adopted in clinical use,
      especially in scientific trials.

PMID- 17229641
TI  - Impact of age on the outcome of patients with chronic myeloid leukemia in late
      chronic phase: results of a phase II study of the GIMEMA CML Working Party.
AB  - To assess the effect of age on response and compliance to treatment in patients
      with chronic myeloid leukemia (CML) we performed a sub-analysis within a phase II
      trial of the GIMEMA CML Working Party (CML/002/STI571). Since the WHO cut-off age
      to define an older patient is 65 years, among the 284 patients considered, we
      identified 226 (80%) younger patients (below 65 years) and 58 (20%) older
      patients (above 65 years) before starting imatinib. Response rates (hematologic
      and cytogenetic) were lower in the older age group but the probabilities of
      progression-free survival and overall survival (median observation time 3 years)
      were the same. Moreover, among complete cytogenetic responders, no differences
      were found in the level of molecular response between the two age groups. As
      might be expected, older patients experienced more adverse events, both
      hematologic and non-hematologic: this worsened compliance did not, however,
      prevent a long-term outcome similar to that of younger patients.

PMID- 17229642
TI  - Recombinant granulocyte-colony stimulating factor as treatment for poor prognosis
      oligoblastic acute myeloid leukemia in elderly patients.
AB  - Twenty-five elderly patients with oligoblastic acute myeloid leukemia (AML)
      received subcutaneous granulocyte colony-stimulating factor (filgrastim) in
      addition to supportive care. Ninety-two percent of the patients had multilineage
      dysplasia, 17% hypoplasia, and 48% a high-risk karyotype. During filgrastim
      treatment neutrophil and platelet counts increased significantly (p<0.0001 and
      (p=0.042), respectively) and 3/13 patients (23%) no longer required transfusions.
      A complete peripheral hematologic response (CHR) was obtained in eight (32%) and
      marrow blast cell clearance (<5%) in five patients (20%), lasting 12 and 10
      months, respectively. Filgrastim caused osteomyalgia and fever in 20% of cases.
      The median survival was 8 months overall, and 15 months in patients who achieved
      a CHR. Filgrastim may be a useful adjunct to supportive care in elderly patients
      with poor-risk AML.

PMID- 17229643
TI  - Idiotype protein vaccination in combination with adjuvant cytokines in patients
      with multiple myeloma--evaluation of T-cell responses by different read-out
      systems.
AB  - Anti-idiotypic T cells were analyzed in myeloma patients (n=18) vaccinated with
      idiotypic protein together with the adjuvant cytokines granulocyte-macrophage
      colony-stimulating factor (GM-CSF) and/or interleukin-12 (IL-12). In the group
      given IL-12/GM-CSF, 78% developed idiotype specific T cells as compared to 22% in
      the group given only IL-12 (proliferation/ELISPOT assays) (p<0.05). The
      percentage of immune-responding patients increased when quantitative real time
      polymerase chain reaction assays for cytokines were included. A predominance of a
      Th1 (IFN-gamma/TNF-alpha) immune response was noted in the IL-12 group while a
      Th2 (IL-5) response prevailed in the IL-12/GM-CSF group (p=0.053). Application of
      multiple read-out systems improved the characterization of the immune response.

PMID- 17229644
TI  - Induction of class II major histocompatibility complex expression in human
      multiple myeloma cells by retinoid.
AB  - Class II major histocompatibility complex (MHC II) is normally silenced in
      plasma/multiple myeloma (MM) cells at the transcriptional level through
      downregulation of class II transactivator (CIITA), allowing MM cells to escape
      from immunological responses. Here we demonstrate that a retinoic acid receptor
      alpha/beta-selective retinoid Am80 (tamibarotene) could induce the expression of
      functional MHC II molecules in human MM cell lines. Am80 upregulated expression
      of the interferon regulatory factor-1 gene, followed by enhancement of CIITA
      expression. This is the first report demonstrating that retinoid can induce the
      expression of MHC II in terminally-differentiated plasma/MM cells.

PMID- 17229645
TI  - Acquired ADAMTS-13 deficiency in pediatric patients with severe sepsis.
AB  - We studied the state of ultra-large von Willebrand factor (ULVWF) proteolysis in
      21 pediatric patients with severe sepsis and found that the overall group of
      patients had moderately reduced ADAMTS-13 activity, but 31% had severe enzymatic
      deficiency. The severe deficiency correlated with greater adhesion activity of
      von Willebrand factor, severity of thrombocytopenia and plasma levels of
      interleukin-6. It also correlated clinically with severity of illness and organ
      dysfunction. These results suggest that ULVWF proteolysis is insufficient in
      septic patients and severely deficient in a subgroup of patients. The deficiency
      may contribute to the development of thrombocytopenia and ischemic organ failure
      associated with sepsis.

PMID- 17229646
TI  - Transient hypoxia and downregulation of circulating prohepcidin concentrations in
      healthy young men.
AB  - To determine the impact of acute hypoxia on prohepcidin concentrations in humans,
      we measured concentrations of this peptide in serum collected during and after a
      transient period (30 min) of hypoxia and during normoxia. Prohepcidin
      concentrations were significantly lower 150 min after the end of hypoxia than
      after normoxia (p=0.028).

PMID- 17229647
TI  - Molecular mechanism of hepcidin deficiency in a patient with juvenile
      hemochromatosis.
AB  - We describe a point mutation creating an additional ATG codon in the 5'
      untranslated region (UTR) of the HAMP gene, in a patient with juvenile
      hemochromatosis. By transient in vitro transfection studies, we provide evidence
      that the additional ATG is functional and prevents normal hepcidin production by
      inducing an aberrant translation initiation of the pre-hepcidin mRNA.

PMID- 17229648
TI  - Sequence-specific modification of a beta-thalassemia locus by small DNA fragments
      in human erythroid progenitor cells.
AB  - Gene therapy has been proposed as a definitive cure of beta-thalassemia. We
      applied a gene targeting approach, based on the introduction of small DNA
      fragments (SDF) into erythroid progenitor cells, to specifically modify the beta
      globin gene sequence at codon 39. The strategy was first tested in normal
      individuals by delivering mutant SDF that were able to produce the beta-39 (C->T)
      mutation. Secondly, wild-type SDF were electroporated into target cells of beta
      3i9/beta-39 b-thalassemic patients to correct the endogenous mutation. In both
      cases, gene modification was assayed by allele-specific polymerase chain reaction
      of DNA and mRNA, by restriction fragment length polymorphism analysis and by
      direct sequencing.

PMID- 17229649
TI  - Cardiac magnetic resonance imaging R2* assessments and analysis of historical
      parameters in patients with transfusion-dependent thalassemia.
AB  - Recent advances in magnetic resonance imaging (MRI) techniques allow the
      assessment of iron overload in tissues 1 especially the heart, 2 in transfusion
      dependent thalassemia patients. The R2* value (1/T2*) recorded in the
      intraventricular septum of the heart indirectly measures the degree of cardiac
      iron load. Applying this new technology we looked at a number of historical and
      biochemical parameters in order to determine their relationship to cardiac iron
      overload and the effect of cardiac iron on functional and structural changes of
      the heart in transfusion-dependent thalassemics.

PMID- 17229650
TI  - Seven novel mutations of the UGT1A1 gene in patients with unconjugated
      hyperbilirubinemia.
AB  - The aim of this study was to identify new pathogenic variations of the UGT1A1
      gene in 11 patients diagnosed with neonatal unconjugated hyperbilirubinemia. We
      describe two cases in which clinically unapparent heterozygotic mutations in the
      UGT1A1 gene may become evident in combination with certain environmental
      conditions or additional genetic defects.

PMID- 17229651
TI  - Risk of thrombosis in patients with essential thrombocythemia and polycythemia
      vera according to JAK2 V617F mutation status.
AB  - We compared the laboratory and clinical findings of 179 patients with essential
      thrombocythemia (ET) and 77 with polycythemia vera (PV) classified according to
      the presence of the JAK2 V617F mutation. A gradient was observed in laboratory
      values between patients with JAK2 wild-type ET, JAK2 V617F ET and PV (all of whom
      carried the JAK2 mutation). The rate of thrombotic complications in JAK2-positive
      ET patients was significantly higher than that in wild-type ET patients and not
      statistically different from that in PV patients.

PMID- 17229652
TI  - Tyrosine kinase mutations of JAK2 are rare events in AML but influence prognosis
      of patients with CBF-leukemias.
AB  - We investigated a large number of acute myeloid leukemia (AML) samples (n=959)
      for the presence of the JAK2 V617F mutation. We found a low incidence of the
      mutation in these AML samples (1%). JAK2 V617F mutations clustered in AML samples
      with an aberrant karyotype (p<0.05). The incidence of JAK2 V617F in patients with
      a core binding factor (CBF) leukemia was 3.6% (p<0.01). Moreover, JAK2 V617F
      mutations in CBF leukemias were associated with an aggressive clinical course
      with 80% of the patients relapsing.

PMID- 17229653
TI  - Pneumocystis jirovecii pneumonia in B-cell lymphoma patients treated with the
      rituximab-CHOEP-14 regimen.
AB  - We report six cases of Pneumocystis jirovecii pneumonia (PCP) verified by
      immunoflourescence/polymerase chain reaction of bronchoalveolar fluid among 46
      lymphoma patients (13%) who received rituximab-CHOEP-14 at our institution. PCP
      prophylaxis should be standard management for this group of patients and also
      considered for patients treated with rituximab-CHOP-14, CHOP-14 or CHOEP-14.

PMID- 17229654
TI  - Severe pulmonary complications after initial treatment with Rituximab for the
      Asian-variant of intravascular lymphoma.
AB  - Rituximab improves response to treatment and outcome for patients with CD20+ B
      cell lymphoma. Herein, however, we report the occurrence of severe pulmonary
      complications shortly after rituximab infusion in three patients with the newly
      diagnosed Asian variant of intravascular lymphoma. It is suggested that patients
      with this subtype of lymphoma are monitored carefully for possible drug reactions
      during the use of rituximab.

PMID- 17229655
TI  - Extramedullary relapse of multiple myeloma associated with a shift in secretion
      from intact immunoglobulin to light chains.
AB  - Biological therapies in multiple myeloma have heralded a new and exciting era for
      treatment to combat this disease. However the evolutionary pressures that these
      drugs place on the microenvironment has resulted in a change in the biological
      behaviour of this malignancy and novel manifestations of relapsed disease. This
      is illustrated in our series of three patients showing fulminant relapse of
      disease with plasmablastic features, an extramedullary predilection and a shift
      in secretion from intact immunoglobulin to free light chains only.

PMID- 17229656
TI  - Comparison of palpation-guided versus ultrasound-guided fine-needle aspiration
      biopsies of thyroid nodules in an outpatient endocrinology practice.
AB  - OBJECTIVE: To investigate the role of thyroid ultrasonography in our outpatient
      endocrine practice. METHODS: We compared the efficacy of ultrasound-guided fine
      needle aspiration biopsy (US-FNAB) of thyroid nodules with that of palpation
      guided aspiration (P-FNAB) and determined the malignancy rates of palpable and
      nonpalpable nodules. All patients referred for assessment of thyroid nodular
      disease from October 1997 through August 2001 were included in the study. Fine
      needle aspirations were performed by palpation guidance until October 1999, after
      which US-FNAB was exclusively performed. All thyroid examinations, ultrasound
      imaging, and aspiration biopsies were performed by the same endocrinologist in an
      office-based setting. Histopathologic and cytologic diagnoses were compared for
      patients who underwent thyroidectomy. RESULTS: A total of 376 nodules in 276
      patients were aspirated during a 47-month period. P-FNAB was used on 157 nodules,
      and US-FNAB was performed on 219 nodules (both procedures were done on 21
      nodules). For palpable thyroid nodules that were resected, the cytologic
      diagnostic accuracy rate was 60.9% and 80% for P-FNAB and US-FNAB, respectively.
      With use of ultrasound guidance, the sensitivity, positive predictive value, and
      negative predictive value increased significantly. In addition, the inadequate
      specimen rate decreased from 11.2% in the P-FNAB group to 7.1% in the US-FNAB
      group. Among the nodules that were not palpable, the malignancy rate was similar
      to that for the palpable thyroid nodules (5.1% versus 6.8%). CONCLUSION: US-FNAB
      improved the cytologic diagnostic accuracy, sensitivity, and positive predictive
      value and reduced the false-negative rate in comparison with P-FNAB. The
      malignancy rate for nonpalpable thyroid nodules was similar to that for palpable
      nodules.

PMID- 17229657
TI  - Assessment of bone and mineral metabolism in inflammatory bowel disease: case
      series and review.
AB  - OBJECTIVE: To determine the prevalence of low bone mass, fractures, and vitamin D
      deficiency and the levels of biochemical markers of mineral metabolism in
      patients with inflammatory bowel disease (IBD). METHODS: Our retrospective study
      consisted of 30 patients with Crohn's disease (CD) and 18 patients with
      ulcerative colitis (UC). Dual-energy x-ray absorptiometry was performed to
      determine bone mineral density at the lumbar spine and hip. Serum calcium,
      phosphorus, parathyroid hormone, 25-hydroxyvitamin D (25-OHD), and 1,25
      dihydroxyvitamin D, urinary N-telopeptide cross-linked collagen type I, and 24
      hour urinary calcium levels were evaluated. RESULTS: On the basis of Z-score
      definitions of low bone mass in the IBD group as a whole, 13 patients (27%) had
      low bone mass at the lumbar spine. Similarly, at the femoral neck, 13 patients
      (27%) had low bone mass. There was a higher prevalence of low bone mass in the UC
      group than in the CD group, consistent with a high prevalence of fractures in
      that group. Of all patients with IBD, 65% had a history of fractures, of which
      23% were atraumatic. Deficiency of 25-OHD was high, with a prevalence of 55% in
      patients with UC and 83% in patients with CD. Secondary hyperparathyroidism,
      defined as a parathyroid hormone level >55 pg/mL in conjunction with a low or
      normal serum calcium and a low 25-OHD level, was present in 50% of patients with
      CD and only 7% of patients with UC. CONCLUSION: Metabolic bone disease and
      fractures are common in IBD. The mean bone mineral density of the spine or
      femoral neck did not differ significantly between patients with CD and those with
      UC. Patients with UC had a higher prevalence of low bone mass, as defined by a Z
      score of less than -2, than did patients with CD, consistent with a high
      prevalence of fractures in the UC group. In contrast, hyperparathyroidism
      attributable to vitamin D deficiency was more prevalent in patients with CD than
      in those with UC. This finding suggests a different etiologic mechanism of low
      bone mass in patients with CD.

PMID- 17229658
TI  - Minimally invasive radio-guided parathyroidectomy in 152 consecutive patients
      with primary hyperparathyroidism.
AB  - OBJECTIVE: To examine the results of minimally invasive radio-guided
      parathyroidectomy (MIRP) in the treatment of patients with primary
      hyperparathyroidism, including factors associated with negative technetium
      labeled sestamibi scanning. METHODS: We retrospectively analyzed the findings in
      a group of 152 consecutive patients encountered during the period 2001 through
      2004. The overall accuracy of preoperative sestamibi scanning was assessed, and
      the success of MIRP was determined on the basis of operative time, duration of
      hospital stay, and rate of complications. RESULTS: All 152 patients underwent
      preoperative sestamibi scanning; 118 (78%) had positive scans and were treated
      with MIRP, whereas 34 (22%) had negative scans and underwent traditional neck
      explorations. Patients with negative sestamibi scans had 5 times the incidence of
      concomitant thyroid disease in comparison with those who had positive sestamibi
      scans (P<0.01), and they had higher rates of parathyroid hyperplasia (26% versus
      0%; P<0.01). In comparison with traditional neck dissection, MIRP-treated
      patients had shorter operative times (38 minutes versus 86 minutes; P<0.01) and
      shorter hospital stays (0.67 day versus 1.09 days; P<0.01). Among the MIRP
      treated patients, 67% were discharged the same day as performance of the
      outpatient surgical procedure. Correction of hypercalcemia was accomplished in
      116 of 118 patients (98%) who underwent MIRP. Complications in the MIRP group
      were low, including 1 postoperative hemorrhage. No cases of recurrent laryngeal
      nerve injury occurred. There were 2 false-positive sestamibi scans (1.3%).
      CONCLUSION: Parathyroid hyperplasia and concomitant thyroid pathologic conditions
      are associated with negative preoperative sestamibi scans. MIRP is applicable in
      78% of patients with primary hyperparathyroidism and is a safe, effective
      operation that results in shorter surgical time, reduced hospital stay, and
      minimal complications.

PMID- 17229659
TI  - Successful treatment of sulfonylurea-induced prolonged hypoglycemia with use of
      octreotide.
AB  - OBJECTIVE: To report the successful use of octreotide in the management of
      prolonged hypoglycemia attributable to therapeutic doses of sulfonylureas.
      METHODS: We present a case series of 6 patients with sulfonylurea-induced
      hypoglycemia, along with pertinent serial laboratory data and review of the
      course of management. RESULTS: Most of our 6 study patients had diabetes
      mellitus, which had been managed with sulfonylurea therapy. In the context of
      renal failure or heart failure (or both), severe, prolonged hypoglycemia
      developed. Intermittent intravenous administration of 50% dextrose did not result
      in a sustained and adequate response. Continuous intravenous administration of
      dextrose-containing solutions was contraindicated because of fluid overload as a
      result of congestive heart failure or renal failure. Administration of
      octreotide, 50 microg subcutaneously every 8 hours, resulted in a prompt and
      sustained resolution of the hypoglycemia. In 3 of the 6 study subjects,
      measurements of insulin and C-peptide levels both before and after treatment
      confirmed the efficacy of the octreotide therapy. CONCLUSION: Our cases
      demonstrate that octreotide proves to be an effective treatment intervention for
      prolonged hypoglycemia caused by therapeutic doses of sulfonylureas. This is the
      first major report of the safe and effective use of octreotide in the management
      of sulfonylurea-induced hypoglycemia outside the emergency department setting.

PMID- 17229660
TI  - Conversion of intravenous insulin infusions to subcutaneously administered
      insulin glargine in patients with hyperglycemia.
AB  - OBJECTIVE: To determine the optimal dose of insulin glargine needed to maintain
      glycemic control in patients undergoing conversion from intravenous regular
      insulin infusions to a subcutaneous insulin regimen. METHODS: Seventy-five
      hospitalized patients receiving continuous insulin infusions were randomized to
      receive 40%, 60%, or 80% of their total daily insulin requirement, calculated
      from the rate during the final 6 hours of the infusion, as insulin glargine at
      the time of conversion to a subcutaneous regimen. Prandial insulin aspart was
      added to the subcutaneous regimen when patients began oral intake, and the dosage
      was left to clinical judgment. Capillary blood glucose monitoring (CBGM) was
      performed before every meal and at bedtime. All CBGM values for the 24-hour
      period after conversion were collected. RESULTS: Three hundred ninety-two CBGM
      values were recorded and analyzed. The mean for all CBGM values during the 24
      hour period after conversion to the subcutaneous insulin regimen was 151.9 +/-
      42.5 mg/dL in the 40% group, 164.0 +/- 41.6 mg/dL in the 60% group, and 153.2 +/-
      66.2 mg/dL in the 80% group (P = 0.66). The percentage of CBGM values in the
      predefined study target range (80 to 140 mg/dL) was 43.2%, 34.8%, and 48% in the
      40%, 60%, and 80% groups, respectively (P = 0.09). Secondary analysis with use of
      a glycemic target of 80 to 150 mg/dL and removal of outliers resulted in CBGM
      values within that range in 58.7%, 44.4%, and 67.6% for the 40%, 60%, and 80%
      groups, respectively (overall, P = 0.001; 40% group versus the 60% group, P =
      0.03; 60% group versus the 80% group, P = 0.0004; and 40% group versus the 80%
      group, P = 0.18). CONCLUSION: Conversion from continuous insulin infusion to
      subcutaneously administered insulin glargine at a dose equal to 80% of the total
      daily insulin requirements resulted in the highest percentage of CBGM values in
      the glycemic target range of 80 to 150 mg/dL within the first 24 hours after
      regimen conversion in comparison with conversion at 40% and 60%, albeit the
      difference between the 40% and 80% groups was not statistically significant.

PMID- 17229661
TI  - Fatal factitious Cushing's syndrome and invasive aspergillosis: case report and
      review of literature.
AB  - OBJECTIVE: To present the first reported fatality from invasive aspergillosis
      related to factitious Cushing's syndrome. METHODS: We summarize the history,
      clinical findings, and outcome in a patient ultimately found to have factitious
      Cushing's syndrome. In addition, the dangers of fulminant infections in untreated
      Cushing's syndrome are analyzed relative to molecular and immunologic aspects,
      and the pertinent literature is reviewed. RESULTS: A 33-year-old female medical
      transcriptionist was admitted with rapidly fatal septic shock and diffuse
      pulmonary infiltrates. Autopsy revealed invasive pulmonary aspergillosis and
      atrophied adrenal cortices. On subsequent investigation, hidden bottles of
      prednisone were found throughout the patient's home. Factitious Cushing's
      syndrome has rarely been described and can be a difficult diagnosis to establish,
      but it is important to recognize this condition because of its potentially
      drastic consequences. Our understanding of the mechanism of immunosuppression
      from glucocorticoids related to the increased risk of invasive fungal infections
      is evolving. Factitious illness can manifest in numerous ways; therefore, health
      care providers in all specialties should be familiar with epidemiologic,
      diagnostic, and treatment considerations for this illness. CONCLUSION:
      Endocrinologists should be aware of the possibility of factitious Cushing's
      syndrome because it can be an elusive and ultimately fatal condition.

PMID- 17229662
TI  - Cushing's Syndrome attributable to ectopic secretion of corticotropin in a
      patient with two neuroendocrine tumors.
AB  - OBJECTIVE: To report a case of ectopic adrenocorticotropic hormone (ACTH)
      syndrome (EAS) in a patient with two distinct neuroendocrine tumors and to
      highlight the difficulties of establishing the differential diagnosis of EAS.
      METHODS: We describe the clinical presentation of the current case, discuss its
      management, and report the results of molecular studies undertaken to determine
      whether the two tumors had a common origin. RESULTS: A 52-year-old woman
      presented with obvious features of Cushing's syndrome. Findings on hormonal
      evaluation were consistent with EAS. Pituitary magnetic resonance imaging
      revealed normal findings. Computed tomographic imaging disclosed two masses, one
      in the lung and one in the pancreas. Somatostatin receptor scintigraphy showed
      uptake only in the pancreatic mass, which was surgically removed. It was a well
      differentiated neuroendocrine tumor, with negative immunostaining for ACTH.
      Hypercortisolemia did not resolve after removal of the pancreatic tumor. The lung
      mass was subsequently excised, and pathology examination showed a carcinoid tumor
      with immunostaining for ACTH. Thereafter, plasma ACTH became immeasurable. The
      two tumors had similar patterns of X-chromosome inactivation; thus, whether they
      arose independently could be neither confirmed nor excluded. CONCLUSION: This
      case demonstrates that, in the presence of more than one neuroendocrine tumor,
      somatostatin receptor scintigraphy may misguide the decision regarding the
      appropriate surgical course in patients with EAS, and it highlights the need for
      accurate studies to determine the source of ACTH in patients with EAS.

PMID- 17229663
TI  - Isolated Langerhans cell histiocytosis in an adult with central diabetes
      insipidus: case report and review of literature.
AB  - OBJECTIVE: To report a case of ectopic adrenocorticotropic hormone (ACTH)
      syndrome (EAS) in a patient with two distinct neuroendocrine tumors and to
      highlight the difficulties of establishing the differential diagnosis of EAS.
      METHODS: We describe the clinical presentation of the current case, discuss its
      management, and report the results of molecular studies undertaken to determine
      whether the two tumors had a common origin. RESULTS: A 52-year-old woman
      presented with obvious features of Cushing's syndrome. Findings on hormonal
      evaluation were consistent with EAS. Pituitary magnetic resonance imaging
      revealed normal findings. Computed tomographic imaging disclosed two masses, one
      in the lung and one in the pancreas. Somatostatin receptor scintigraphy showed
      uptake only in the pancreatic mass, which was surgically removed. It was a well
      differentiated neuroendocrine tumor, with negative immunostaining for ACTH.
      Hypercortisolemia did not resolve after removal of the pancreatic tumor. The lung
      mass was subsequently excised, and pathology examination showed a carcinoid tumor
      with immunostaining for ACTH. Thereafter, plasma ACTH became immeasurable. The
      two tumors had similar patterns of X-chromosome inactivation; thus, whether they
      arose independently could be neither confirmed nor excluded. CONCLUSION: This
      case demonstrates that, in the presence of more than one neuroendocrine tumor,
      somatostatin receptor scintigraphy may misguide the decision regarding the
      appropriate surgical course in patients with EAS, and it highlights the need for
      accurate studies to determine the source of ACTH in patients with EAS.

PMID- 17229664
TI  - Complete androgen insensitivity syndrome in a black South African family: a
      clinical and molecular investigation.
AB  - OBJECTIVE: To present the first report of a clinical and molecular investigation
      of a black South African family with complete androgen insensitivity syndrome
      (CAIS). METHODS: Biochemical and chromosomal analyses were performed. In
      addition, the molecular study included microsatellite analysis and DNA
      sequencing. RESULTS: The index case, an unmarried 21-year-old black phenotypic
      female patient with primary amenorrhea, was identified in the Division of
      Endocrinology at a tertiary hospital affiliated with the University of the
      Witwatersrand. A detailed family history identified further potentially affected
      members (on the basis of primary amenorrhea), who were also included in the
      study. A total of 13 family members, including 6 affected subjects, were involved
      in the molecular study. All affected persons had a 46,XY karyotype, female
      phenotype, and hormonal profiles commensurate with their clinical diagnosis. The
      androgen receptor gene in an affected patient was examined for mutations by DNA
      sequencing. Mutation screening was extended to other family members. The genetic
      basis for CAIS in this large family is the missense mutation, D732Y, in exon 5 of
      the androgen receptor ligand-binding domain. CONCLUSION: To our knowledge, this
      is the first case report of CAIS in South Africa in which molecular genetic
      techniques were used to substantiate the clinical diagnosis. The findings in this
      study have implications for genetic counseling in this family.

PMID- 17229665
TI  - Bisphosphonate treatment of tumor-induced hypercalcemia in a toddler: case report
      and review of related literature.
AB  - OBJECTIVE: To describe the initial manifestations and treatment of parathyroid
      hormone-related peptide (PTH-rP)-induced hypercalcemia in a toddler with a
      malignant rhabdoid tumor. METHODS: We report a case of a 2-year-old boy
      presenting with poor appetite, lethargy, and a 1.5-kg weight loss during a 2-week
      period. On examination, the child was found to have a right upper quadrant
      abdominal mass. Laboratory studies revealed severe hypercalcemia. We review the
      patients' clinical course and management of hypercalcemia. RESULTS: Initial
      evaluation revealed no cardiovascular instability. An abdominal mass was
      identified on physical examination. Initial laboratory studies revealed elevated
      levels of total and ionized calcium, low phosphorus, microcytic anemia, and
      elevated erythrocyte sedimentation rate. Saline diuresis with furosemide was
      begun. Abdominal ultrasonography revealed a large right renal tumor. Because of
      refractory hypercalcemia, intravenously administered bisphosphonate was used.
      Within 12 hours after bisphosphonate infusion, the serum calcium level declined
      from 14.9 mg/dL to 10.9 mg/dL. The furosemide dose was decreased and finally
      discontinued 2 days after bisphosphonate administration. Because of development
      of a femoral thrombosis, definitive surgical intervention was delayed. During
      that time, serum calcium levels again increased and necessitated administration
      of a second bisphosphonate dose. At surgical treatment, a right renal tumor was
      identified, and frozen section pathology revealed a rhabdoid tumor. After tumor
      resection, calcium levels were stable. Other laboratory studies performed at
      admission revealed suppressed PTH, normal vitamin D and calcitonin levels, and
      elevated PTH-rP. CONCLUSION: Hypercalcemia in a toddler is a rare event and can
      be attributable to humoral factors released by malignant tumors. Hypercalcemia in
      the pediatric population can be treated effectively with bisphosphonates when
      conservative measures fail.

PMID- 17229666
TI  - Low serum alkaline phosphatase activity and pathologic fracture: case report and
      brief review of hypophosphatasia diagnosed in adulthood.
AB  - OBJECTIVE: To describe an elderly patient with low serum alkaline phosphatase
      (ALP) activity detected after a pathologic fracture and to characterize
      hypophosphatasia in adult patients. METHODS: We present a case report of a 64
      year-old woman, who was referred after sustaining an atraumatic femoral fracture
      treated successfully with intramedullary nailing. Clinical, biochemical,
      radiologic, and molecular studies explore the differential diagnosis of her
      hypophosphatasemia, and the features, diagnosis, and management of the adult form
      of hypophosphatasia are reviewed. RESULTS: Physical examination of our patient
      was revealing only for short stature. Bone mineral density evaluated by dual
      energy x-ray absorptiometry was unremarkable. Biochemical investigations showed
      normal calcium, elevated inorganic phosphate, and low ALP levels in serum. In
      light of the hypophosphatasemia and pathologic fracture, the serum pyridoxal 5'
      phosphate concentration was measured and found to be considerably elevated, a
      substantiation of the diagnosis of hypophosphatasia. Analysis of the gene
      encoding the "tissue-nonspecific" isoenzyme of ALP (TNSALP) demonstrated a novel,
      heterozygous, missense mutation causing her disorder. CONCLUSION:
      Hypophosphatasia is a rare inborn error of metabolism due to a deactivating
      mutation (or mutations) of the gene encoding TNSALP, in turn leading to global
      deficiency of TNSALP activity and inadequate skeletal mineralization and
      fractures. Our patient illustrates the importance of low serum ALP activity in
      the assessment of patients with fractures. No established treatment exists for
      hypophosphatasia, but the correct diagnosis should help to avoid the use of
      traditional therapies for osteoporosis or osteomalacia, which would be
      ineffective or potentially harmful.

PMID- 17229667
TI  - Cardiovascular risk in patients with growth hormone deficiency: effects of growth
      hormone substitution.
AB  - OBJECTIVE: To review the literature on the increased cardiovascular risk in
      patients with growth hormone (GH) deficiency and the positive effects of GH
      replacement. METHODS: We analyze the factors that contribute to cardiovascular
      risk in GH deficiency, including body composition and lipid profile, and
      summarize GH treatment strategies and results described in the literature.
      RESULTS: The prominent clinical finding in patients with GH deficiency is the
      increased abdominal fat, even in patients with normal weight. Cardiac ejection
      volume tends to be decreased, and arterial distensibility is diminished. The
      lipid status is also worsened, accompanied by increased inflammatory markers,
      such as highly sensitive C-reactive protein. Typically, GH treatment reduces
      visceral fat and increases muscle mass, changes that diminish cardiovascular
      risk. Because of direct effects as well as increased hemodynamic performance and
      increased blood volume, cardiac performance is improved. With GH therapy, total
      cholesterol and low-density lipoprotein levels decrease by 10% to 20%, and
      inflammatory markers such as C-reactive protein decline. Carbohydrate metabolism
      during moderate to long-term treatment is minimally affected, although obese
      patients with GH deficiency on rare occasion may have hyperglycemia or even
      diabetes. CONCLUSION: The relevance of the beneficial effects of GH on the
      cardiovascular system is strongly suggested but not fully proved. The results in
      a large cohort of GH-treated patients (the KIMS or Pharmacia and Upjohn
      International Metabolic Surveillance database) demonstrated no difference in
      cardiovascular risk in comparison with that in a control population after a mean
      of 3 years of treatment.

PMID- 17229668
TI  - Hajdu-Cheney syndrome in a 19-year-old man.

PMID- 17229669
TI  - Idle thoughts from an addled mind. The sheriff and city hall.

PMID- 17229671
TI  - Visual vignette.

PMID- 17229672
TI  - Visual vignette.

PMID- 17229673
TI  - Cytokine-mediated regulation of urea transporters during experimental
      endotoxemia.
AB  - Acute renal failure (ARF) is a frequent complication of sepsis and has a high
      mortality. Sepsis-induced ARF is known to be associated with significant
      impairment of tubular capacity. However, the pathogenesis of endotoxemic tubular
      dysfunction with failure of urine concentration is poorly understood. Urea plays
      an important role in the urinary concentrating mechanism and expression of the
      urea transporters UT-A1, UT-A2, UT-A3, UT-A4, and UT-B is essential for tubular
      urea reabsorption. The present study attempts to assess the regulation of renal
      urea transporters during severe inflammation in vivo. Lipopolysaccharide-(LPS)
      injected mice presented with reduced glomerular filtration rate, fractional urea
      excretion, and inner medulla osmolality associated with a marked decrease in
      expression of all renal urea transporters. Similar alterations were observed
      after application of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta,
      interferon (IFN)-gamma, or IL-6. LPS-induced downregulation of urea transporters
      was not affected in knockout mice with deficient TNF-alpha, IL-receptor-1, IFN
      gamma, or IL-6. Glucocorticoid treatment inhibited LPS-induced increases of
      tissue TNF-alpha, IL-1beta, IFN-gamma, or IL-6 concentration, diminished LPS
      induced renal dysfunction, and attenuated the downregulation of renal urea
      transporters. Renal ischemia induced by renal artery clipping did not influence
      the expression of urea transporters. Our data demonstrate that renal urea
      transporters are downregulated by severe inflammation, which likely accounts for
      tubular dysfunction. Furthermore, they suggest that the downregulation of renal
      urea transporters during LPS-induced ARF is mediated by proinflammatory cytokines
      and is independent from renal ischemia because of sepsis-induced hypotension.

PMID- 17229674
TI  - Angiotensin II-induced genomic damage in renal cells can be prevented by
      angiotensin II type 1 receptor blockage or radical scavenging.
AB  - Hypertensive patients exhibit elevated cancer incidence, especially of cancers of
      the kidney. Elevated levels of ANG II, the active peptide of the renin
      angiotensin system, regulating blood pressure and cardiovascular homeostasis, are
      known to cause hypertension and kidney diseases. There is evidence that ANG II is
      an activator of NAD(P)H oxidase, leading to the formation of free radicals, which
      are known to participate in the induction of DNA damage. This study was
      undertaken to characterize ANG II-induced DNA damage. DNA damage was measured by
      comet assay and micronucleus frequency test. Incubation of pig kidney cells (LLC
      PK(1)) in vitro with ANG II concentrations between 85 and 340 nM led to a 6- to
      15-fold increase of DNA damage compared with the control as revealed by comet
      assay analysis. Micronuclei were induced about fourfold compared with the control
      in pig and rat kidney cells (LLC-PK(1), NRK) and in human promyelocytic cells (HL
      60). ANG II-induced DNA damage could be prevented by coincubation with the ANG II
      type 1 receptor blocker candesartan and the antioxidants N-acetylcysteine and
      alpha-tocopherol. The ANG II type 2 receptor antagonist PD123319 could not reduce
      ANG II-induced DNA damage. Measurement of reactive oxygen species (ROS) by flow
      cytometry showed an enhanced formation after exposure to ANG II and a reduction
      of ROS after candesartan, N-acetylcysteine, and alpha-tocopherol. The present
      findings support our hypothesis that ANG II causes DNA damage via ANG II type 1
      receptor binding and subsequent formation of oxidative stress.

PMID- 17229675
TI  - Rapid isolation of urinary exosomal biomarkers using a nanomembrane
      ultrafiltration concentrator.
AB  - Urinary exosomes are excreted from all nephron segments and may serve as
      biomarkers for classifying renal diseases. Isolation of urinary exosomes by the
      established ultracentrifugation method has some limitations for use in a clinical
      laboratory. We sought a rapid and simple way to obtain urinary exosomes. We used
      a commercially available nanomembrane concentrator to enrich exosomes from urine
      by centrifugation at 3,000 g for 10-30 min. Urinary exosomal markers tumor
      susceptibility gene 101, aquaporin-2, neuron-specific enolase, annexin V,
      angiotensin-converting enzyme, and podocalyxin (PODXL) were recovered from the
      nanomembrane concentrator and detected by Western blotting, and typical features
      of urinary vesicles were found by electron microscopy. Exosomal markers were
      detected in as little as 0.5 ml of urine. By the nanomembrane method, exosomal
      proteins could be recovered from urine samples frozen at -80 degrees C or
      refrigerated overnight at 4 degrees C then stored at -80 degrees C. By enriching
      exosomes we could detect PODXL, a podocyte marker, which decreased by 71% in five
      male patients with focal segmental glomerulosclerosis and abundant proteinuria.
      We conclude that 1) use of a nanomembrane concentrator simplifies and accelerates
      the enrichment of urinary exosomes; and 2) the nanomembrane concentrator can
      concentrate exosomal proteins from clinical urine samples. This enhanced method
      may accelerate the translation of urinary exosomal biomarkers from bench to
      bedside for the diagnosis, classification, and prognostication of renal diseases.

PMID- 17229676
TI  - COX-2 activity transiently contributes to increased water and NaCl excretion in
      the polyuric phase after release of ureteral obstruction.
AB  - Release of bilateral ureteral obstruction (BUO) is associated with reduced
      expression of renal aquaporins (AQPs), polyuria, and impairment of urine
      concentrating capacity. Recently, we demonstrated that 24 h of BUO is associated
      with increased cyclooxygenase (COX)-2 expression in the inner medulla (IM) and
      that selective COX-2 inhibition prevents downregulation of AQP2. In the present
      study, we tested the hypothesis that COX-2 activity increases in the
      postobstructive phase and that this increase in COX-2 activity contributes to
      polyuria and impaired urine-concentrating capacity. We examined the effect of the
      selective COX-2 inhibitor parecoxib (5 mg.kg(-1).day(-1) via osmotic minipumps)
      on renal functions and protein abundance of AQP2, AQP3, Na-K-2Cl cotransporter
      type 2 (NKCC2), and Na-K-ATPase 3 days after release of BUO. At 3 days after
      release of BUO, rats exhibited polyuria, dehydration and urine and IM tissue
      osmolality were decreased. There were inverse changes of COX-1 and COX-2 in the
      IM: COX-2 mRNA, protein, and activity increased, while COX-1 mRNA and protein
      decreased. Parecoxib reduced urine output 1 day after release of BUO, but sodium
      excretion and glomerular filtration rate were unchanged. Parecoxib normalized
      urinary PGE(2) and PGI(2) excretion and attenuated downregulation of AQP2 and
      AQP3, while phosphorylated AQP2 and NKCC2 remained suppressed. Parecoxib did not
      improve urine-concentrating capacity in response to 24 h of water deprivation. We
      conclude that decreased NKCC2 and collapse of the IM osmotic gradient, together
      with suppressed phosphorylated AQP2, are likely causes for the impaired urine
      concentrating capacity and that COX-2 activity is not likely to mediate these
      changes in the chronic postobstructive phase after ureteral obstruction.

PMID- 17229677
TI  - Novel role of AQP-1 in NO-dependent vasorelaxation.
AB  - Nitric oxide (NO) produced by endothelial cells diffuses to vascular smooth
      muscle cells to cause dilatation of the renal vasculature and other vessels.
      Although it is generally assumed that NO moves from cell to cell by free
      diffusion, we recently showed that aquaporin-1 (AQP-1) transports NO across cell
      membranes. AQP-1 is expressed in endothelial and vascular smooth muscle cells. We
      hypothesized that diffusion of NO into vascular smooth muscle cells and out of
      endothelial cells is facilitated by AQP-1, and transport of NO by AQP-1 is
      involved in endothelium-dependent relaxation. In intact aortic rings from AQP-1 
      /- mice, vasorelaxation induced by acetylcholine (which increases endogenous NO)
      was reduced (P < 0.0001 vs. control). No differences were found in the relaxation
      caused by intracellular delivery of NO or intracellular cGMP between strains. In
      endothelium-denuded aortic rings from AQP-1 -/- mice, the vasorelaxant capability
      of NO released in the extracellular space was reduced (P < 0.0001 vs. control).
      Influx of NO (5 microM) into vascular smooth muscle cells was 0.17 +/- 0.02
      f.u./s for control and 0.07 +/- 0.01 f.u./s for AQP-1 -/- mice, 62% lower (P <
      0.002). NO released by endothelial cells in response to 1 microM acetylcholine
      was 96.2 +/- 17.7 pmol NO/mg for control and 41.9 +/- 13.4 pmol NO/mg for AQP-1 
      /- mice, 56% reduction (P < 0.04). NOS3 expression was 1.33 +/- 0.29 O.D. units
      for control and 3.84 +/- 0.76 O.D. units for AQP-1 -/- mice, 188% increase (P <
      0.01). We conclude that 1) AQP-1 facilitates NO influx into vascular smooth
      muscle cells, 2) AQP-1 facilitates NO diffusion out of endothelial cells, and 3)
      transport of NO by AQP-1 is required for full expression of endothelium-dependent
      relaxation.

PMID- 17229678
TI  - Nephrogenic diabetes insipidus in mice caused by deleting COOH-terminal tail of
      aquaporin-2.
AB  - In mammals, the hormonal regulation of water homeostasis is mediated by the
      aquaporin-2 water channel (Aqp2) of the collecting duct (CD). Vasopressin induces
      redistribution of Aqp2 from intracellular vesicles to the apical membrane of CD
      principal cells, accompanied by increased water permeability. Mutations of AQP2
      gene in humans cause both recessive and dominant nephrogenic diabetes insipidus
      (NDI), a disease in which the kidney is unable to concentrate urine in response
      to vasopressin. In this study, we generated a line of mice with the distal COOH
      terminal tail of the Aqp2 deleted (Aqp2(Delta230)), including the protein kinase
      A phosphorylation site (S256), but still retaining the putative apical
      localization signal (221-229) at the COOH-terminal. Mice heterozygous for the
      truncation appear normal. Homozygotes are viable to adulthood, with reduced urine
      concentrating capacity, increased urine output, decreased urine osmolality, and
      increased daily water consumption. Desmopressin increased urine osmolality in
      wild-type mice but had no effect on Aqp2(Delta230/Delta230) mice. Kidneys from
      affected mice showed CD and pelvis dilatation and papillary atrophy. By
      immunohistochemical and immunoblot analyses using antibody against the NH(2)
      terminal region of the protein Aqp2(Delta230/Delta230) mice had a markedly
      reduced protein abundance. Expression of the truncated protein in MDCK cells was
      consistent with a small amount of functional expression but no stimulation. Thus
      we have generated a mouse model of NDI that may be useful in studying the
      physiology and potential therapy of this disease.

PMID- 17229679
TI  - Assessment of renal autoregulation.
AB  - The kidney displays highly efficient autoregulation so that under steady-state
      conditions renal blood flow (RBF) is independent of blood pressure over a wide
      range of pressure. Autoregulation occurs in the preglomerular microcirculation
      and is mediated by two, perhaps three, mechanisms. The faster myogenic mechanism
      and the slower tubuloglomerular feedback contribute both directly and
      interactively to autoregulation of RBF and of glomerular capillary pressure.
      Multiple experiments have been used to study autoregulation and can be considered
      as variants of two basic designs. The first measures RBF after multiple stepwise
      changes in renal perfusion pressure to assess how a biological condition or
      experimental maneuver affects the overall pressure-flow relationship. The second
      uses time-series analysis to better understand the operation of multiple
      controllers operating in parallel on the same vascular smooth muscle. There are
      conceptual and experimental limitations to all current experimental designs so
      that no one design adequately describes autoregulation. In particular, it is
      clear that the efficiency of autoregulation varies with time and that most
      current techniques do not adequately address this issue. Also, the time-varying
      and nonadditive interaction between the myogenic mechanism and tubuloglomerular
      feedback underscores the difficulty of dissecting their contributions to
      autoregulation. We consider the modulation of autoregulation by nitric oxide and
      use it to illustrate the necessity for multiple experimental designs, often
      applied iteratively.

PMID- 17229680
TI  - Role of the coronavirus E viroporin protein transmembrane domain in virus
      assembly.
AB  - Coronavirus envelope (E) proteins are small (approximately 75- to 110-amino-acid)
      membrane proteins that have a short hydrophilic amino terminus, a relatively long
      hydrophobic membrane domain, and a long hydrophilic carboxy-terminal domain. The
      protein is a minor virion structural component that plays an important, not fully
      understood role in virus production. It was recently demonstrated that the
      protein forms ion channels. We investigated the importance of the hydrophobic
      domain of the mouse hepatitis coronavirus (MHV) A59 E protein. Alanine scanning
      insertion mutagenesis was used to examine the effect of disruption of the domain
      on virus production in the context of the virus genome by using a MHV A59
      infectious clone. Mutant viruses exhibited smaller plaque phenotypes, and virus
      production was significantly crippled. Analysis of recovered viruses suggested
      that the structure of the presumed alpha-helical structure and positioning of
      polar hydrophilic residues within the predicted transmembrane domain are
      important for virus production. Generation of viruses with restored wild-type
      helical pitch resulted in increased virus production, but some exhibited
      decreased virus release. Viruses with the restored helical pitch were more
      sensitive to treatment with the ion channel inhibitor hexamethylene amiloride
      than were the more crippled parental viruses with the single alanine insertions,
      suggesting that disruption of the transmembrane domain affects the functional
      activity of the protein. Overall the results indicate that the transmembrane
      domain plays a crucial role during biogenesis of virions.

PMID- 17229681
TI  - An RNA-binding protein, hnRNP A1, and a scaffold protein, septin 6, facilitate
      hepatitis C virus replication.
AB  - Hepatitis C virus (HCV) is a positive-sense single-stranded RNA virus. NS5b is an
      RNA-dependent RNA polymerase that polymerizes the newly synthesized RNA. HCV
      likely uses host proteins for its replication, similar to other RNA viruses. To
      identify the cellular factors involved in HCV replication, we searched for
      cellular proteins that interact with the NS5b protein. HnRNP A1 and septin 6
      proteins were identified by coimmunoprecipitation and yeast two-hybrid screening,
      respectively. Interestingly, septin 6 protein also interacts with hnRNP A1.
      Moreover, hnRNP A1 interacts with the 5'-nontranslated region (5' NTR) and the 3'
      NTR of HCV RNA containing the cis-acting elements required for replication.
      Knockdown of hnRNP A1 and overexpression of C-terminally truncated hnRNP A1
      reduced HCV replication. In addition, knockdown of septin 6 and overexpression of
      N-terminally truncated septin 6 inhibited HCV replication. These results indicate
      that the host proteins hnRNP A1 and septin 6 play important roles in the
      replication of HCV through RNA-protein and protein-protein interactions.

PMID- 17229682
TI  - Mapping of the VP40-binding regions of the nucleoprotein of Ebola virus.
AB  - Expression of Ebola virus nucleoprotein (NP) in mammalian cells leads to the
      formation of helical structures, which serve as a scaffold for the nucleocapsid.
      We recently found that NP binding with the matrix protein VP40 is important for
      nucleocapsid incorporation into virions (T. Noda, H. Ebihara, Y. Muramoto, K.
      Fujii, A. Takada, H. Sagara, J. H. Kim, H. Kida, H. Feldmann, and Y. Kawaoka,
      PLoS Pathog. 2:e99, 2006). To identify the region(s) on the NP molecule required
      for VP40 binding, we examined the interaction of a series of NP deletion mutants
      with VP40 biochemically and ultrastructurally. We found that both termini of NP
      (amino acids 2 to 150 and 601 to 739) are essential for its interaction with VP40
      and for its incorporation into virus-like particles (VLPs). We also found that
      the C terminus of NP is important for nucleocapsid incorporation into virions. Of
      interest is that the formation of NP helices, which involves the N-terminal 450
      amino acids of NP, is dispensable for NP incorporation into VLPs. These findings
      enhance our understanding of Ebola virus assembly and in so doing move us closer
      to the identification of targets for the development of antiviral compounds to
      combat Ebola virus infection.

PMID- 17229683
TI  - Formation of a multiple protein complex on the adenovirus packaging sequence by
      the IVa2 protein.
AB  - During adenovirus virion assembly, the packaging sequence mediates the
      encapsidation of the viral genome. This sequence is composed of seven functional
      units, termed A repeats. Recent evidence suggests that the adenovirus IVa2
      protein binds the packaging sequence and is involved in packaging of the genome.
      Study of the IVa2-packaging sequence interaction has been hindered by difficulty
      in purifying the protein produced in virus-infected cells or by recombinant
      techniques. We report the first purification of a recombinant untagged version of
      the adenovirus IVa2 protein and characterize its binding to the packaging
      sequence in vitro. Our data indicate that there is more than one IVa2 binding
      site within the packaging sequence and that IVa2 binding to DNA requires the A
      repeat consensus, 5'-TTTG-(N(8))-CG-3'. Furthermore, we present evidence that
      IVa2 forms a multimeric complex on the packaging sequence. These data support a
      model in which adenovirus DNA packaging occurs via the formation of a IVa2
      multiprotein complex on the packaging sequence.

PMID- 17229684
TI  - Cytoplasmic localization of the ORF2 protein of hepatitis E virus is dependent on
      its ability to undergo retrotranslocation from the endoplasmic reticulum.
AB  - Hepatitis E virus (HEV) is a positive-strand RNA virus that is prevalent in much
      of the developing world. ORF2 is the major capsid protein of HEV. Although ORF2
      is an N-linked glycoprotein, it is abundantly located in the cytoplasm in
      addition to having membrane and surface localization. The mechanism by which ORF2
      protein obtains access to the cytoplasm is unknown. In this report, we prove that
      initially all ORF2 protein is present in the endoplasmic reticulum and a fraction
      of it becomes retrotranslocated to the cytoplasm. The ability of ORF2 to be
      retrotranslocated is dependent on its glycosylation status and follows the
      canonical dislocation pathway. However, in contrast to general substrates of the
      dislocation pathway, retrotranslocated ORF2 protein is not a substrate of the 26S
      proteasome complex and is readily detectable in the cytoplasm in the absence of
      any protease inhibitor, suggesting that the retrotranslocated protein is stable
      in the cytoplasm. This study thus defines the pathway by which ORF2 obtains
      access to the cytoplasm.

PMID- 17229685
TI  - Assembly of hepatitis delta virus: particle characterization, including the
      ability to infect primary human hepatocytes.
AB  - Efficient assembly of hepatitis delta virus (HDV) was achieved by cotransfection
      of Huh7 cells with two plasmids: one to provide expression of the large, middle,
      and small envelope proteins of hepatitis B virus (HBV), the natural helper of
      HDV, and another to initiate replication of the HDV RNA genome. HDV released into
      the media was assayed for HDV RNA and HBV envelope proteins and characterized by
      rate-zonal sedimentation, immunoaffinity purification, electron microscopy, and
      the ability to infect primary human hepatocytes. Among the novel findings were
      that (i) immunostaining for delta antigen 6 days after infection with 300 genome
      equivalents (GE) per cell showed only 1% of cells as infected, but this was
      increased to 16% when 5% polyethylene glycol was present during infection; (ii)
      uninfected cells did not differ from infected cells in terms of albumin
      accumulation or the presence of E-cadherin at cell junctions; and (iii) sensitive
      quantitative real-time PCR assays detected HDV replication even when the
      multiplicity of infection was 0.2 GE/cell. In the future, this HDV assembly and
      infection system can be further developed to better understand the mechanisms
      shared by HBV and HDV for attachment and entry into host cells.

PMID- 17229686
TI  - Expression of rotavirus NSP4 alters the actin network organization through the
      actin remodeling protein cofilin.
AB  - Rotavirus is a major cause of infantile gastroenteritis with a multifactorial
      pathogenesis. As with many other pathogens, rotavirus infection and replication
      leads to rearrangement of the cytoskeleton with disorganization of cytoskeletal
      elements such as actin and cytokeratin through a calcium-dependent process that
      has not been fully characterized. The rotavirus enterotoxin NSP4, shown
      previously to elevate intracellular calcium levels when added exogenously as well
      as when expressed intracellularly, is a key player in intracellular calcium
      regulation during rotavirus infection. Here, we investigated the role NSP4 may
      play in actin rearrangement. Expression of NSP4 fused to enhanced green
      fluorescent protein (NSP4-EGFP), but not expression of EGFP alone, caused
      stabilization of long cellular projections in fully confluent HEK 293 cells.
      Cells expressing NSP4-EGFP for 24 h were also resistant to cell rounding induced
      by cytochalasin D. Quantification of filamentous actin (F-actin) content by using
      rhodamine-conjugated phalloidin and flow cytometry showed an elevated F-actin
      content in NSP4-EGFP-expressing and rotavirus-infected cells in comparison with
      that in nonexpressing and noninfected cells. Normalization of intracellular
      calcium levels prevented alterations of F-actin content. Observed changes in F
      actin amounts correlated with the increased activation of the actin-remodeling
      protein cofilin. These calcium-dependent actin rearrangements induced by
      intracellular NSP4 expression may contribute to rotavirus pathogenesis by
      interfering with cellular processes dependent on subcortical actin remodeling,
      including ion transport and viral release.

PMID- 17229687
TI  - Sialic acid on herpes simplex virus type 1 envelope glycoproteins is required for
      efficient infection of cells.
AB  - Herpes simplex virus type 1 (HSV-1) envelope proteins are posttranslationally
      modified by the addition of sialic acids to the termini of the glycan side
      chains. Although gC, gD, and gH are sialylated, it is not known whether sialic
      acids on these envelope proteins are functionally important. Digestion of sucrose
      gradient purified virions for 4 h with neuraminidases that remove both alpha2,3
      and alpha2,6 linked sialic acids reduced titers by 1,000-fold. Digestion with a
      alpha2,3-specific neuraminidase had no effect, suggesting that alpha2,6-linked
      sialic acids are required for infection. Lectins specific for either alpha2,3 or
      alpha2,6 linkages blocked attachment and infection to the same extent. In
      addition, the mobility of gH, gB, and gD in sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis gels was altered by digestion with either alpha2,3 specific
      neuraminidase or nonspecific neuraminidases, indicating the presence of both
      linkages on these proteins. The infectivity of a gC-1-null virus, DeltagC2-3, was
      reduced to the same extent as wild-type virus after neuraminidase digestion, and
      attachment was not altered. Neuraminidase digestion of virions resulted in
      reduced VP16 translocation to the nucleus, suggesting that the block occurred
      between attachment and entry. These results show for the first time that sialic
      acids on HSV-1 virions play an important role in infection and suggest that
      targeting virion sialic acids may be a valid antiviral drug development strategy.

PMID- 17229688
TI  - Maintenance of endoplasmic reticulum (ER) homeostasis in herpes simplex virus
      type 1-infected cells through the association of a viral glycoprotein with PERK,
      a cellular ER stress sensor.
AB  - In the efforts of viruses to dominate and control critical cellular pathways,
      viruses generate considerable intracellular stress within their hosts. In
      particular, the capacity of resident endoplasmic reticulum (ER) chaperones to
      properly process the acute increase in client protein load is significantly
      challenged. Such alterations typically induce the unfolded protein response, one
      component of which acts through IRE1 to restore ER homeostasis by expanding the
      folding capabilities, whereas the other arm activates the eIF-2alpha (alpha
      subunit of eukaryotic initiation factor 2) kinase PERK to transiently arrest
      production of new polypeptide clientele. Viruses, such as herpes simplex virus
      type 1 (HSV-1), however, go to great lengths to prevent the inhibition of
      translation resulting from eIF-2alpha phosphorylation. Here, we establish that
      PERK, but not IRE1, resists activation by acute ER stress in HSV-1-infected
      cells. This requires the ER luminal domain of PERK, which associates with the
      viral glycoprotein gB. Strikingly, gB regulates viral protein accumulation in a
      PERK-dependent manner. This is the first description of a virus-encoded PERK
      specific effector and defines a new strategy by which viruses are able to
      maintain ER homeostasis.

PMID- 17229689
TI  - Innate immune response to adenoviral vectors is mediated by both Toll-like
      receptor-dependent and -independent pathways.
AB  - Recombinant adenoviral vectors have been widely used for gene therapy
      applications and as vaccine vehicles for treating infectious diseases such as
      human immunodeficiency virus disease. The innate immune response to adenoviruses
      represents the most significant hurdle in clinical application of adenoviral
      vectors for gene therapy, but it is an attractive feature for vaccine
      development. How adenovirus activates innate immunity remains largely unknown.
      Here we showed that adenovirus elicited innate immune response through the
      induction of high levels of type I interferons (IFNs) by both plasmacytoid
      dendritic cells (pDCs) and non-pDCs such as conventional DCs and macrophages. The
      innate immune recognition of adenovirus by pDCs was mediated by Toll-like
      receptor 9 (TLR9) and was dependent on MyD88, whereas that by non-pDCs was TLR
      independent through cytosolic sensing of adenoviral DNA. Furthermore, type I IFNs
      were pivotal in innate and adaptive immune responses to adenovirus in vivo, and
      type I IFN blockade diminished immune responses, resulting in more stable
      transgene expression and reduction of inflammation. These findings indicate that
      adenovirus activates innate immunity by its DNA through TLR-dependent and 
      independent pathways in a cell type-specific fashion, and they highlight a
      critical role for type I IFNs in innate and adaptive immune responses to
      adenoviral vectors. Our results that suggest strategies to interfere with type I
      IFN pathway may improve the outcome of adenovirus-mediated gene therapy, whereas
      approaches to activate the type I IFN pathway may enhance vaccine potency.

PMID- 17229690
TI  - A second receptor binding site on human parainfluenza virus type 3 hemagglutinin
      neuraminidase contributes to activation of the fusion mechanism.
AB  - The hemagglutinin-neuraminidase (HN) protein of paramyxoviruses carries out three
      discrete activities that each affect the ability of HN to promote viral fusion
      and entry: receptor binding, receptor cleaving (neuraminidase), and triggering of
      the fusion protein. The interrelationship between the receptor binding and fusion
      triggering functions of HN has not been clear. For human parainfluenza type 3
      (HPIV3), one bifunctional site on HN can carry out both receptor binding and
      neuraminidase activities, and this site's receptor binding can be inhibited by
      the small receptor analog zanamivir. We now report experimental evidence,
      complemented by computational data, for a second receptor binding site near the
      HPIV3 HN dimer interface. This second binding site can mediate receptor binding
      even in the presence of zanamivir, and it differs from the second receptor
      binding site of the paramyxovirus Newcastle disease virus in its function and its
      relationship to the primary binding site. This second binding site of HPIV3 HN is
      involved in triggering F. We suggest that the two receptor binding sites on HPIV3
      HN each contribute in distinct ways to virus-cell interaction; one is the
      multifunctional site that contains both binding and neuraminidase activities, and
      the other contains binding activity and also is involved in fusion promotion.

PMID- 17229691
TI  - Ribonucleocapsid formation of severe acute respiratory syndrome coronavirus
      through molecular action of the N-terminal domain of N protein.
AB  - Conserved among all coronaviruses are four structural proteins: the matrix (M),
      small envelope (E), and spike (S) proteins that are embedded in the viral
      membrane and the nucleocapsid phosphoprotein (N), which exists in a
      ribonucleoprotein complex in the lumen. The N-terminal domain of coronaviral N
      proteins (N-NTD) provides a scaffold for RNA binding, while the C-terminal domain
      (N-CTD) mainly acts as oligomerization modules during assembly. The C terminus of
      the N protein anchors it to the viral membrane by associating with M protein. We
      characterized the structures of N-NTD from severe acute respiratory syndrome
      coronavirus (SARS-CoV) in two crystal forms, at 1.17 A (monoclinic) and at 1.85 A
      (cubic), respectively, resolved by molecular replacement using the homologous
      avian infectious bronchitis virus (IBV) structure. Flexible loops in the solution
      structure of SARS-CoV N-NTD are now shown to be well ordered around the beta
      sheet core. The functionally important positively charged beta-hairpin protrudes
      out of the core, is oriented similarly to that in the IBV N-NTD, and is involved
      in crystal packing in the monoclinic form. In the cubic form, the monomers form
      trimeric units that stack in a helical array. Comparison of crystal packing of
      SARS-CoV and IBV N-NTDs suggests a common mode of RNA recognition, but they
      probably associate differently in vivo during the formation of the
      ribonucleoprotein complex. Electrostatic potential distribution on the surface of
      homology models of related coronaviral N-NTDs suggests that they use different
      modes of both RNA recognition and oligomeric assembly, perhaps explaining why
      their nucleocapsids have different morphologies.

PMID- 17229692
TI  - Murine norovirus 1 infection is associated with histopathological changes in
      immunocompetent hosts, but clinical disease is prevented by STAT1-dependent
      interferon responses.
AB  - Human noroviruses are the major cause of nonbacterial epidemic gastroenteritis
      worldwide. However, little is known regarding their pathogenesis or the immune
      responses that control them because until recently there has been no small animal
      model or cell culture system of norovirus infection. We recently reported the
      discovery of the first murine norovirus, murine norovirus 1 (MNV-1), and its
      cultivation in macrophages and dendritic cells in vitro. We further defined
      interferon receptors and the STAT-1 molecule as critical in both resistance to
      MNV-1-induced disease in vivo and control of virus growth in vitro. To date,
      neither histopathological changes upon infection nor viral replication in wild
      type mice has been shown. Here we extend our studies to demonstrate that MNV-1
      replicates and rapidly disseminates to various tissues in immunocompetent mice
      and that infection is restricted by STAT1-dependent interferon responses at the
      levels of viral replication and virus dissemination. Infection of wild-type mice
      is associated with histopathological alterations in the intestine (mild
      inflammation) and the spleen (red pulp hypertrophy and white pulp activation);
      viral dissemination to the spleen, liver, lung, and lymph nodes; and low-level
      persistent infection in the spleen. STAT-1 inhibits viral replication in the
      intestine, prevents virus-induced apoptosis of intestinal cells and splenocytes,
      and limits viral dissemination to peripheral tissues. These findings demonstrate
      that murine norovirus infection of wild-type mice is associated with initial
      enteric seeding and subsequent extraintestinal spread, and they provide
      mechanistic evidence of the role of STAT-1 in controlling clinical norovirus
      induced disease.

PMID- 17229693
TI  - A replication-competent adenovirus-human immunodeficiency virus (Ad-HIV) tat and
      Ad-HIV env priming/Tat and envelope protein boosting regimen elicits enhanced
      protective efficacy against simian/human immunodeficiency virus SHIV89.6P
      challenge in rhesus macaques.
AB  - We previously demonstrated that replication-competent adenovirus (Ad)-simian
      immunodeficiency virus (SIV) recombinant prime/protein boost regimens elicit
      potent immunogenicity and strong, durable protection of rhesus macaques against
      SIV(mac251). Additionally, native Tat vaccines have conferred strong protection
      against simian/human immunodeficiency virus SHIV(89.6P) challenge of cynomolgus
      monkeys, while native, inactivated, or vectored Tat vaccines have failed to
      elicit similar protective efficacy in rhesus macaques. Here we asked if priming
      rhesus macaques with replicating Ad-human immunodeficiency virus (HIV) tat and
      boosting with the Tat protein would elicit protection against SHIV(89.6P). We
      also evaluated a Tat/Env regimen, adding an Ad-HIV env recombinant and envelope
      protein boost to test whether envelope antibodies would augment acute-phase
      protection. Further, expecting cellular immunity to enhance chronic viremia
      control, we tested a multigenic group: Ad-HIV tat, -HIV env, -SIV gag, and -SIV
      nef recombinants and Tat, Env, and Nef proteins. All regimens were immunogenic. A
      hierarchy was observed in enzyme-linked immunospot responses (with the strongest
      response for Env, followed by Gag, followed by Nef, followed by Tat) and antibody
      titers (with the highest titer for Env, followed by Tat, followed by Nef,
      followed by Gag). Following intravenous SHIV(89.6P) challenge, all macaques
      became infected. Compared to controls, no protection was seen in the Tat-only
      group, confirming previous reports for rhesus macaques. However, the multigenic
      group blunted acute viremia by approximately 1 log (P = 0.017), and both the
      multigenic and Tat/Env groups reduced chronic viremia by 3 and 4 logs,
      respectively, compared to controls (multigenic, P = 0.0003; Tat/Env, P < 0.0001).
      The strikingly greater reduction in the Tat/Env group than in the multigenic
      group (P = 0.014) was correlated with Tat and Env binding antibodies. Since
      prechallenge anti-Env antibodies lacked SHIV(89.6P)-neutralizing activity, other
      functional anti-Env and anti-Tat activities are under investigation, as is a
      possible synergy between the Tat and Env immunogens.

PMID- 17229694
TI  - Inhibition of cellular 2'-5' oligoadenylate synthetase by the herpes simplex
      virus type 1 Us11 protein.
AB  - Among the many host genes induced by virus infection and interferon, the
      eIF2alpha protein kinase PKR and the 2'-5' oligoadenylate synthetase (OAS) are
      both activated by double-stranded RNA (dsRNA) produced in virus-infected cells.
      Furthermore, each is a critical component that independently acts to inhibit
      virus replication and thereby contributes to the establishment of an antiviral
      state. As part of their tactics to foil host defense mechanisms, some viruses
      prevent the induction of interferon-responsive genes at the level of
      transcription. Other viruses, such as herpes simplex virus type 1 (HSV-1), can
      additionally replicate in interferon-treated cells and must also evade the
      actions of host defense proteins such as PKR and OAS that have been previously
      synthesized and merely await detection of an activating signal. Whereas HSV-1
      gene products gamma(1)34.5 and Us11 are required for viral replication in
      interferon-treated cells and both act in a temporally coordinated manner during
      infection to counteract PKR, HSV-1 functions that target OAS have not been
      described. Here, we demonstrate that HSV-1 infection inhibits 2'-5'
      oligoadenylate synthesis in interferon-stimulated primary human cells. The OAS
      inhibiting activity is generated late in the virus' productive life cycle and
      requires the Us11 gene product. Moreover, we establish that the Us11 protein is
      sufficient to block OAS activation in extracts from uninfected, interferon
      treated cells. Inhibition of OAS specifically requires the Us11 dsRNA-binding
      domain, suggesting a mechanism that, in part, relies on sequestering available
      dsRNA produced during infection. Thus, in addition to PKR and its protein
      activator, PACT, the HSV-1 Us11 gene product is able to counteract the activity
      of OAS, a third cellular protein critical for host defense.

PMID- 17229695
TI  - The mimivirus genome encodes a mitochondrial carrier that transports dATP and
      dTTP.
AB  - Members of the mitochondrial carrier family have been reported in eukaryotes
      only, where they transport metabolites and cofactors across the mitochondrial
      inner membrane to link the metabolic pathways of the cytosol and the matrix. The
      genome of the giant virus Mimiviridae mimivirus encodes a member of the
      mitochondrial carrier family of transport proteins. This viral protein has been
      expressed in Lactococcus lactis and is shown to transport dATP and dTTP. As the
      1.2-Mb double-stranded DNA mimivirus genome is rich in A and T residues, we
      speculate that the virus is using this protein to target the host mitochondria as
      a source of deoxynucleotides for its replication.

PMID- 17229696
TI  - Mutations that decrease DNA binding of the processivity factor of the herpes
      simplex virus DNA polymerase reduce viral yield, alter the kinetics of viral DNA
      replication, and decrease the fidelity of DNA replication.
AB  - The processivity subunit of the herpes simplex virus DNA polymerase, UL42, is
      essential for viral replication and possesses both Pol- and DNA-binding
      activities. Previous studies demonstrated that the substitution of alanine for
      each of four arginine residues, which reside on the positively charged surface of
      UL42, resulted in decreased DNA binding affinity and a decreased ability to
      synthesize long-chain DNA by the polymerase. In this study, the effects of each
      substitution on the production of viral progeny, viral DNA replication, and DNA
      replication fidelity were examined. Each substitution mutant was able to
      complement the replication of a UL42 null mutant in transient complementation
      assays and to support the replication of plasmid DNA containing herpes simplex
      virus type 1 (HSV-1) origin sequences in transient DNA replication assays. Mutant
      viruses containing each substitution and a lacZ insertion in a nonessential
      region of the genome were constructed and characterized. In single-cycle growth
      assays, the mutants produced significantly less progeny virus than the control
      virus containing wild-type UL42. Real-time PCR assays revealed that these UL42
      mutants synthesized less viral DNA during the early phase of infection.
      Interestingly, during the late phase of infection, the mutant viruses synthesized
      larger amounts of viral DNA than the control virus. The frequencies of mutations
      of the virus-borne lacZ gene increased significantly in the substitution mutants
      compared to those observed for the control virus. These results demonstrate that
      the reduced DNA binding of UL42 is associated with significant effects on virus
      yields, viral DNA replication, and replication fidelity. Thus, a processivity
      factor can influence replication fidelity in mammalian cells.

PMID- 17229697
TI  - Poxvirus-encoded gamma interferon binding protein dampens the host immune
      response to infection.
AB  - Ectromelia virus (ECTV), a natural mouse pathogen and the causative agent of
      mousepox, is closely related to variola virus (VARV), which causes smallpox in
      humans. Mousepox is an excellent surrogate small-animal model for smallpox. Both
      ECTV and VARV encode a multitude of host response modifiers that target
      components of the immune system and that are thought to contribute to the high
      mortality rates associated with infection. Like VARV, ECTV encodes a protein
      homologous to the ectodomain of the host gamma interferon (IFN-gamma) receptor 1.
      We generated an IFN-gamma binding protein (IFN-gammabp) deletion mutant of ECTV
      to study the role of viral IFN-gammabp (vIFN-gammabp) in host-virus interaction
      and also to elucidate the contribution of this molecule to the outcome of
      infection. Our data show that the absence of vIFN-gammabp does not affect virus
      replication per se but does have a profound effect on virus replication and
      pathogenesis in mice. BALB/c mice, which are normally susceptible to infection
      with ECTV, were able to control replication of the mutant virus and survive
      infection. Absence of vIFN-gammabp from ECTV allowed the generation of an
      effective host immune response that was otherwise diminished by this viral
      protein. Mice infected with a vIFN-gammabp deletion mutant virus, designated ECTV
      IFN-gammabp(Delta), produced increased levels of IFN-gamma and generated robust
      cell-mediated and antibody responses. Using several strains of mice that exhibit
      differential degrees of resistance to mousepox, we show that recovery or death
      from ECTV infection is determined by a balance between the host's ability to
      produce IFN-gamma and the virus' ability to dampen its effects.

PMID- 17229698
TI  - Upregulation of indoleamine 2,3-dioxygenase in hepatitis C virus infection.
AB  - Indoleamine 2,3-dioxygenase (IDO) is induced by proinflammatory cytokines and by
      CTLA-4-expressing T cells and constitutes an important mediator of peripheral
      immune tolerance. In chronic hepatitis C, we found upregulation of IDO expression
      in the liver and an increased serum kynurenine/tryptophan ratio (a reflection of
      IDO activity). Huh7 cells supporting hepatitis C virus (HCV) replication
      expressed higher levels of IDO mRNA than noninfected cells when stimulated with
      gamma interferon or when cocultured with activated T cells. In infected
      chimpanzees, hepatic IDO expression decreased in animals that cured the
      infection, while it remained high in those that progressed to chronicity. For
      both patients and chimpanzees, hepatic expression of IDO and CTLA-4 correlated
      directly. Induction of IDO may dampen T-cell reactivity to viral antigens in
      chronic HCV infection.

PMID- 17229699
TI  - Immunoglobulin A (IgA) is a natural ligand of hepatitis A virus cellular receptor
      1 (HAVCR1), and the association of IgA with HAVCR1 enhances virus-receptor
      interactions.
AB  - The hepatitis A virus cellular receptor 1 (HAVCR1/TIM1), a member of the T-cell
      immunoglobulin mucin (TIM) family, is an important atopy susceptibility gene in
      humans. The exact natural function of HAVCR1/TIM1 and the inverse association
      between HAV infection and prevention of atopy are not well understood. To
      identify natural ligands of human HAVCR1/TIM1, we used an expression cloning
      strategy based on the binding of dog cells transfected with a human lymph node
      cDNA library to a HAVCR1/TIM1 Fc fusion protein. The transfected cells that bound
      to the human HAVCR1/TIM1 Fc contained cDNA of human immunoglobulin alpha 1 heavy
      (Igalpha1) and lambda light (Iglambda) chain and secreted human IgA1lambda
      antibody that bound to the cell surface. Cotransfection of the isolated Igalpha1
      and Iglambda cDNAs to naive dog cells resulted in the secretion of IgA1lambda
      that bound to HAVCR1/TIM1 Fc but not to a poliovirus receptor Fc fusion protein
      in a capture enzyme-linked immunosorbent assay. The interaction of HAVCR1/TIM1
      with IgA was inhibited by monoclonal antibodies (MAbs) against Igalpha1 and
      Iglambda, excess IgA1lambda, or anti-HAVCR1/TIM1 MAb. IgA did not inhibit HAV
      infection of African green monkey cells, suggesting that the IgA and the virus
      binding sites are in different epitopes on HAVCR1/TIM1. IgA enhanced
      significantly the neutralization of HAV by HAVCR1/TIM1 Fc. Our results indicate
      that IgA1lambda is a specific ligand of HAVCR1/TIM1 and that their association
      has a synergistic effect in virus-receptor interactions.

PMID- 17229700
TI  - Proteolytic processing of the Ebola virus glycoprotein is not critical for Ebola
      virus replication in nonhuman primates.
AB  - Enveloped viruses often require cleavage of a surface glycoprotein by a cellular
      endoprotease such as furin for infectivity and virulence. Previously, we showed
      that Ebola virus glycoprotein does not require the furin cleavage motif for virus
      replication in cell culture. Here, we show that there are no appreciable
      differences in disease progression, hematology, serum biochemistry, virus titers,
      or lethality in nonhuman primates infected with an Ebola virus lacking the furin
      recognition sequence compared to those infected with wild-type virus. We conclude
      that glycoprotein cleavage by subtilisin-like endoproteases is not critical for
      Ebola virus infectivity and virulence in nonhuman primates.

PMID- 17229701
TI  - Frequency and phenotype of JC virus-specific CD8+ T lymphocytes in the peripheral
      blood of patients with progressive multifocal leukoencephalopathy.
AB  - JC virus (JCV)-specific CD8+ cytotoxic T lymphocytes (CTL) are associated with a
      favorable outcome in patients with progressive multifocal leukoencephalopathy
      (PML) and cross-recognize the polyomavirus BK virus (BKV). We sought to determine
      the frequency and phenotype in fresh blood of CD8+ T cells specific for two
      A*0201-restricted JCV epitopes, VP1(p36) and VP1(p100), and assess their impact
      on JC and BK viremia and viruria in 15 healthy subjects, eight human
      immunodeficiency virus-positive (HIV+) individuals, and nine HIV+ patients with
      PML (HIV+ PML patients) classified as survivors. After magnetic pre-enrichment of
      CD8+ T cells, epitope-specific cells ranged from 0.001% to 0.022% [corrected] by
      tetramer staining, with no significant difference among the three study groups.
      By use of seven-color flow cytometry, there was no predominant differentiation
      phenotype subset among JCV-specific CD8+ T cells in healthy individuals, HIV+
      subjects, or HIV+ PML patients. However, in one HIV+ PML patient studied in the
      acute phase, there was a majority of activated effector memory cells. BKV DNA was
      undetectable in all blood samples by quantitative PCR, while a low JC viral load
      was found in the blood of only one HIV+ and two HIV+ PML patients. JCV and BKV
      DNA were detected in 33.3% and 13.3% of all urine samples, respectively,
      independent of the presence of JCV-specific CTL. The detection of JCV DNA in the
      urine was associated with the presence of a JCV VP1(p100) CTL response.
      Immunotherapies aiming at increasing the cellular immune response against JCV may
      be valuable in the treatment of HIV+ individuals with PML.

PMID- 17229702
TI  - 5'-proximal hot spot for an inducible positive-to-negative-strand template switch
      by coronavirus RNA-dependent RNA polymerase.
AB  - Coronaviruses have a positive-strand RNA genome and replicate through the use of
      a 3' nested set of subgenomic mRNAs each possessing a leader (65 to 90
      nucleotides [nt] in length, depending on the viral species) identical to and
      derived from the genomic leader. One widely supported model for leader
      acquisition states that a template switch takes place during the generation of
      negative-strand antileader-containing templates used subsequently for subgenomic
      mRNA synthesis. In this process, the switch is largely driven by canonical
      heptameric donor sequences at intergenic sites on the genome that match an
      acceptor sequence at the 3' end of the genomic leader. With experimentally placed
      22-nt-long donor sequences within a bovine coronavirus defective interfering (DI)
      RNA we have shown that matching sites occurring anywhere within a 65-nt-wide 5'
      proximal genomic acceptor hot spot (nt 33 through 97) can be used for production
      of templates for subgenomic mRNA synthesis from the DI RNA. Here we report that
      with the same experimental approach, template switches can be induced in trans
      from an internal site in the DI RNA to the negative-strand antigenome of the
      helper virus. For these, a 3'-proximal 89-nt acceptor hot spot on the viral
      antigenome (nt 35 through 123), largely complementary to that described above,
      was found. Molecules resulting from these switches were not templates for
      subgenomic mRNA synthesis but, rather, ambisense chimeras potentially exceeding
      the viral genome in length. The results suggest the existence of a coronavirus 5'
      proximal partially double-stranded template switch-facilitating structure of
      discrete width that contains both the viral genome and antigenome.

PMID- 17229703
TI  - Correct capsid assembly mediated by a conserved YXXLGL motif in prototype foamy
      virus Gag is essential for infectivity and reverse transcription of the viral
      genome.
AB  - Unlike other retrovirus Gag proteins, the prototype foamy virus (PFV) p71(g)(ag)
      protein is not processed into mature matrix (MA), capsid (CA), and nucleocapsid
      (NC) subunits. Little information about sequence motifs involved in FV capsid
      assembly and release is available. The recent analysis of candidate L-domain
      motifs in PFV Gag identified an evolutionarily conserved YXXL sequence motif with
      a potential function in capsid assembly. Here we provide support for the
      hypothesis that this motif does not function like a conventional L domain, by
      demonstrating that, unlike the PFV Gag PSAP L-domain motif, it cannot be
      functionally replaced by heterologous L-domain sequences. Furthermore, mutation
      of individual amino acids Y(464), I(466), L(467), and L(469), but not E(465), to
      alanine led to reduced particle release and production of noninfectious, aberrant
      capsid structures, although relative structural protein incorporation and
      processing were not affected. In contrast, mutation of G(468) to alanine resulted
      in an intermediate, temperature-sensitive phenotype characterized by reduced
      particle release and reduced infectivity. Despite similar relative RNA genome
      incorporation for all mutants, analysis and quantification of particle-associated
      viral nucleic acids demonstrated defects in genomic reverse transcription for all
      the noninfectious mutants, a process that, unlike that of orthoretroviruses, in
      the case of FVs takes place in the virus-producing cell. In correlation with the
      reduced infectivity, the G(468)A mutant displayed an intermediate level of
      genomic reverse transcription. Taken together, these results demonstrate that the
      conserved YXXLGL motif in PFV Gag is involved in correct capsid assembly, which
      in turn is essential for reverse transcription of the FV genome.

PMID- 17229704
TI  - Influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate
      antiapoptotic signaling responses.
AB  - Recently we have shown that influenza A virus infection leads to activation of
      the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and that this cellular
      reaction is dependent on the expression of the viral nonstructural protein 1
      (NS1). These data also suggested that PI3K activation confers a virus-supporting
      activity at intermediate stages of the infection cycle. So far it is not known
      which process is regulated by the kinase that supports virus replication. It is
      well established that upon infection with influenza A virus, the expression of
      the viral NS1 keeps the induction of beta interferon and the apoptotic response
      within a tolerable limit. On a molecular basis, this activity of NS1 has been
      suggested to preclude the activation of cellular double-stranded RNA receptors as
      well as impaired modulation of mRNA processing. Here we present a novel mode of
      action of the NS1 protein to suppress apoptosis induction. NS1 binds to and
      activates PI3K, which results in the activation of the PI3K effector Akt. This
      leads to a subsequent inhibition of caspase 9 and glycogen synthase-kinase 3beta
      and limitation of the virus-induced cell death program. Thus, NS1 not only blocks
      but also activates signaling pathways to ensure efficient virus replication.

PMID- 17229705
TI  - An extended stem-loop 1 is necessary for human immunodeficiency virus type 2
      replication and affects genomic RNA encapsidation.
AB  - Genomic RNA encapsidation in lentiviruses is a highly selective and regulated
      process. The unspliced RNA molecules are selected for encapsidation from a pool
      of many different viral and cellular RNA species. Moreover, two molecules are
      encapsidated per viral particle, where they are found associated as a dimer. In
      this study, we demonstrate that a 10-nucleotide palindromic sequence (pal)
      located at the 3' end of the psi encapsidation signal is critical for human
      immunodeficiency virus type 2 (HIV-2) replication and affects genomic RNA
      encapsidation. We used short-term and long-term culture of pal-mutated viruses in
      permissive C8166 cells and their phenotypic reversion to show the existence of a
      structurally extended SL1 during HIV-2 replication, formed by the interaction of
      the 3' end of the pal within psi with a motif located downstream of SL1. The stem
      extending HIV-2 SL1 is structurally similar to stem B described for HIV-1 SL1.
      Despite the high degree of phylogenetic conservation, these results show that
      mutant viruses are viable when the autocomplementary nature of the pal sequence
      is disrupted, but not without a stable stem B. Our observations show that
      formation of the extended SL1 is necessary during viral replication and
      positively affects HIV-2 genomic RNA encapsidation. Sequestration of part of the
      packaging signal into SL1 may be a means of regulating its presentation during
      the replication cycle.

PMID- 17229706
TI  - Contrasting effects of human, canine, and hybrid adenovirus vectors on the
      phenotypical and functional maturation of human dendritic cells: implications for
      clinical efficacy.
AB  - Antipathogen immune responses create a balance between immunity, tolerance, and
      immune evasion. However, during gene therapy most viral vectors are delivered in
      substantial doses and are incapable of expressing gene products that reduce the
      host's ability to detect transduced cells. Gene transfer efficacy is also
      modified by the in vivo transduction of dendritic cells (DC), which notably
      increases the immunogenicity of virions and vector-encoded genes. In this study,
      we evaluated parameters that are relevant to the use of canine adenovirus
      serotype 2 (CAV-2) vectors in the clinical setting by assaying their effect on
      human monocyte-derived DC (hMoDC). We compared CAV-2 to human adenovirus (HAd)
      vectors containing the wild-type virion, functional deletions in the penton base
      RGD motif, and the CAV-2 fiber knob. In contrast to the HAd type 5 (HAd5)-based
      vectors, CAV-2 poorly transduced hMoDC, provoked minimal upregulation of major
      histocompatibility complex class I/II and costimulatory molecules (CD40, CD80,
      and CD86), and induced negligible morphological changes indicative of DC
      maturation. Functional maturation assay results (e.g., reduced antigen uptake;
      tumor necrosis factor alpha, interleukin-1beta [IL-1beta], gamma interferon [IFN
      gamma], IL-10, IL-12, and IFN-alpha/beta secretion; and stimulation of
      heterologous T-cell proliferation) were also significantly lower for CAV-2. Our
      data suggested that this was due, in part, to the use of an alternative receptor
      and a block in vesicular escape. Additionally, HAd5 vector-induced hMoDC
      maturation was independent of the aforementioned cytokines. Paradoxically, an
      HAd5/CAV-2 hybrid vector induced the greatest phenotypical and functional
      maturation of hMoDC. Our data suggest that CAV-2 and the HAd5/CAV-2 vector may be
      the antithesis of Adenoviridae immunogenicity and that each may have specific
      clinical advantages.

PMID- 17229707
TI  - Dysregulation of the ubiquitin-proteasome system by curcumin suppresses
      coxsackievirus B3 replication.
AB  - Curcumin (diferuloylmethane), a natural polyphenolic compound extracted from the
      spice turmeric, has been reported to have anti-inflammatory, antioxidant, and
      antiproliferative properties by modulating multiple cellular machineries. It
      inhibits several intracellular signaling pathways, including the mitogen
      activated protein kinases (MAPKs), casein kinase II (CKII), and the COP9
      signalosome (CSN), in various cell types. It has also been recently demonstrated
      that exposure to curcumin leads to the dysregulation of the ubiquitin-proteasome
      system (UPS). Coxsackievirus infection is associated with various diseases,
      including myocarditis and dilated cardiomyopathy. In searching for new antiviral
      agents against coxsackievirus, we found that treatment with curcumin
      significantly reduced viral RNA expression, protein synthesis, and virus titer
      and protected cells from virus-induced cytopathic effect and apoptosis. We
      further demonstrated that reduction of viral infection by curcumin was unlikely
      due to inhibition of CVB3 binding to its receptors or CVB3-induced activation of
      MAPKs. Moreover, gene silencing of CKII and Jab1, a component of CSN, by small
      interfering RNAs did not inhibit the replication of coxsackievirus, suggesting
      that the antiviral action of curcumin is independent of these pathways. Finally,
      we showed that curcumin treatment reduced both the 20S proteasome proteolytic
      activities and the cellular deubiquitinating activities, leading to increased
      accumulation of ubiquitinated proteins and decreased protein levels of free
      ubiquitin. We have recently demonstrated that the UPS-mediated protein
      degradation and/or modification plays a critical role in the regulation of
      coxsackievirus replication. Thus, our results suggest an important antiviral
      effect of curcumin wherein it potently inhibits coxsackievirus replication
      through dysregulation of the UPS.

PMID- 17229708
TI  - The carboxy-terminal domain of glycoprotein N of human cytomegalovirus is
      required for virion morphogenesis.
AB  - Glycoproteins M and N (gM and gN, respectively) are among the few proteins that
      are conserved across the herpesvirus family. The function of the complex is
      largely unknown. Whereas deletion from most alphaherpesviruses has marginal
      effects on the replication of the respective viruses, both proteins are essential
      for replication of human cytomegalovirus (HCMV). We have constructed a series of
      mutants in gN to study the function of this protein. gN of HCMV is a type I
      glycoprotein containing a short carboxy-terminal domain of 14 amino acids,
      including two cysteine residues directly adjacent to the predicted transmembrane
      anchor at positions 125 and 126. Deletion of the entire carboxy-terminal domain
      as well as substitution with the corresponding region from alpha herpesviruses or
      mutations of both cysteine residues resulted in a replication-incompetent virus.
      Recombinant viruses containing point mutations of either cysteine residue could
      be generated. These viruses were profoundly defective for replication. Complex
      formation of the mutant gNs with gM and transport of the complex to the viral
      assembly compartment appeared unaltered compared to the wild type. However, in
      infected cells, large numbers of capsids accumulated in the cytoplasm that failed
      to acquire an envelope. Transiently expressed gN was shown to be modified by
      palmitic acid at both cysteine residues. In summary, our data suggest that the
      carboxy-terminal domain of gN plays a critical role in secondary envelopment of
      HCMV and that palmitoylation of gN appears to be essential for function in
      secondary envelopment of HCMV and virus replication.

PMID- 17229709
TI  - Ability of hyaluronidase 2 to degrade extracellular hyaluronan is not required
      for its function as a receptor for jaagsiekte sheep retrovirus.
AB  - Jaagsiekte sheep retrovirus (JSRV) uses hyaluronidase 2 (Hyal2) as a cell entry
      receptor. By making inactivating mutations to the catalytic residues of human
      Hyal2, we found that hyaluronidase activity was dispensable for its receptor
      function. The affinities of the JSRV envelope glycoprotein for Hyal2 and the
      Hyal2 mutant were similar, and hyaluronan did not block either high-affinity
      interaction or virus infection. While generating the Hyal2 mutant, we discovered
      that our previous analysis of the hyaluronidase activity of Hyal2 was affected by
      a contaminating hyaluronan lyase, which we have identified as the occlusion
      derived baculovirus E66 protein of the recombinant baculovirus used to produce
      Hyal2. We now report that purified human Hyal2 is a weak acid-active
      hyaluronidase.

PMID- 17229710
TI  - New way of regulating alternative splicing in retroviruses: the promoter makes a
      difference.
AB  - Alternative splicing has been recognized as a major mechanism for creating
      proteomic diversity from a limited number of genes. However, not all determinants
      regulating this process have been characterized. Using subviral human
      immunodeficiency virus (HIV) env constructs we observed an enhanced splicing of
      the RNA when expression was under control of the cytomegalovirus (CMV) promoter
      instead of the HIV long terminal repeat (LTR). We extended these observations to
      LTR- or CMV-driven murine leukemia proviruses, suggesting that retroviral LTRs
      are adapted to inefficient alternative splicing at most sites in order to
      maintain balanced gene expression.

PMID- 17229711
TI  - Immediate activation fails to rescue efficient human immunodeficiency virus
      replication in quiescent CD4+ T cells.
AB  - Unlike activated T cells, quiescent CD4+ T cells have shown resistance to human
      immunodeficiency virus (HIV) infection due to a block in the early events of the
      viral life cycle. To further investigate the nature of this block, we infected
      quiescent CD4+ T cells with HIV-1(NL4-3) and immediately stimulated them.
      Compared to activated (prestimulated) cells, these poststimulated cells showed
      slightly decreased viral entry and delays in the completion of reverse
      transcription. However, the relative efficiency of integration was similar to
      that of prestimulated cells. Together, this resulted in decreased expression of
      tat/rev mRNA and synthesis of viral protein. Furthermore, based on cell cycle
      staining and BrdU incorporation, poststimulated cells expressing viral protein
      failed to initiate a second round of their cell cycle, independently of Vpr
      mediated arrest. Together, these data demonstrate that the early stages of the
      HIV life cycle are inefficient in these poststimulated cells and that efficient
      replication cannot be induced by subsequent activation.

PMID- 17229712
TI  - The glycoprotein cytoplasmic tail of Uukuniemi virus (Bunyaviridae) interacts
      with ribonucleoproteins and is critical for genome packaging.
AB  - We have analyzed the importance of specific amino acids in the cytoplasmic tail
      of the glycoprotein G(N) for packaging of ribonucleoproteins (RNPs) into virus
      like particles (VLPs) of Uukuniemi virus (UUK virus), a member of the
      Bunyaviridae family. In order to study packaging, we added the G(N)/G(C)
      glycoprotein precursor (p110) to a polymerase I-driven minigenome rescue system
      to generate VLPs that are released into the supernatant. These particles can
      infect new cells, and reporter gene expression can be detected. To determine the
      role of UUK virus glycoproteins in RNP packaging, we performed an alanine scan of
      the glycoprotein G(N) cytoplasmic tail (amino acids 1 to 81). First, we
      discovered three regions in the tail (amino acids 21 to 25, 46 to 50, and 71 to
      81) which are important for minigenome transfer by VLPs. Further mutational
      analysis identified four amino acids that were important for RNP packaging. These
      amino acids are essential for the binding of nucleoproteins and RNPs to the
      glycoprotein without affecting the morphology of the particles. No segment
      specific interactions between the RNA and the cytoplasmic tail could be observed.
      We propose that VLP systems are useful tools for analyzing protein-protein
      interactions important for packaging of viral genome segments, assembly, and
      budding of other members of the Bunyaviridae family.

PMID- 17229713
TI  - Targeting of the Sendai virus C protein to the plasma membrane via a peptide-only
      membrane anchor.
AB  - Several cellular proteins are synthesized in the cytosol on free ribosomes and
      then associate with membranes due to the presence of short peptide sequences.
      These membrane-targeting sequences contain sites to which lipid chains are
      attached, which help direct the protein to a particular membrane domain and
      anchor it firmly in the bilayer. The intracellular concentration of these
      proteins in particular cellular compartments, where their interacting partners
      are also concentrated, is essential to their function. This paper reports that
      the apparently unmodified N-terminal sequence of the Sendai virus C protein
      (MPSFLKKILKLRGRR . . .; letters in italics represent hydrophobic residues;
      underlined letters represent basic residues, which has a strong propensity to
      form an amphipathic alpha-helix in a hydrophobic environment) also function as a
      membrane targeting signal and membrane anchor. Moreover, the intracellular
      localization of the C protein at the plasma membrane is essential for inducing
      the interferon-independent phosphorylation of Stat1 as part of the viral program
      to prevent the cellular antiviral response.

PMID- 17229714
TI  - ALY is a common coactivator of RUNX1 and c-Myb on the type B leukemogenic virus
      enhancer.
AB  - Type B leukemogenic virus (TBLV), a mouse mammary tumor virus (MMTV) variant,
      often induces T-cell leukemias and lymphomas by c-myc activation following viral
      DNA integration. Transfection assays using a c-myc reporter plasmid indicated
      that the TBLV long terminal repeat (LTR) enhancer is necessary for T-cell
      specific increases in basal reporter activity. The sequence requirements for this
      effect were studied using mutations of the 62-bp enhancer region in an MMTV LTR
      reporter vector. Deletion of a nuclear factor A-binding site dramatically reduced
      reporter activity in Jurkat T cells. However, a 41-bp enhancer missing the RUNX1
      site still retained minimal enhancer function. DNA affinity purification using a
      TBLV enhancer oligomer containing the RUNX1 binding site followed by mass
      spectrometry resulted in the identification of ALY. Subsequent experiments
      focused on the reconstitution of enhancer activity in epithelial cells. ALY
      overexpression synergized with RUNX1B on TBLV enhancer activity, and synergism
      required the RUNX1B-binding site. A predicted c-Myb binding site in the enhancer
      was confirmed after c-myb overexpression elevated TBLV LTR reporter activity, and
      overexpression of c-Myb and RUNX1B together showed additive effects on reporter
      gene levels. ALY also synergized with c-Myb, and coimmunoprecipitation
      experiments demonstrated an interaction between ALY and c-Myb. These experiments
      suggest a central role for ALY in T-cell enhancer function and oncogene
      activation.

PMID- 17229715
TI  - Quantitative proteomics profiling of sarcomere associated proteins in limb and
      extraocular muscle allotypes.
AB  - The sarcomere is the major structural and functional unit of striated muscle.
      Approximately 65 different proteins have been associated with the sarcomere, and
      their exact composition defines the speed, endurance, and biology of each
      individual muscle. Past analyses relied heavily on electrophoretic and
      immunohistochemical techniques, which only allow the analysis of a small fraction
      of proteins at a time. Here we introduce a quantitative label-free, shotgun
      proteomics approach to differentially quantitate sarcomeric proteins from
      microgram quantities of muscle tissue in a fast and reliable manner by liquid
      chromatography and mass spectrometry. The high sequence similarity of some
      sarcomeric proteins poses a problem for shotgun proteomics because of limitations
      in subsequent database search algorithms in the exclusive assignment of peptides
      to specific isoforms. Therefore multiple sequence alignments were generated to
      improve the identification of isoform specific peptides. This methodology was
      used to compare the sarcomeric proteome of the extraocular muscle allotype to
      limb muscle. Extraocular muscles are a unique group of highly specialized muscles
      with distinct biochemical, physiological, and pathological properties. We were
      able to quantitate 40 sarcomeric proteins; although the basic sarcomeric proteins
      in extraocular muscle are similar to those in limb muscle, key proteins
      stabilizing the connection of the Z-bands to thin filaments and the costamere are
      augmented in extraocular muscle and may represent an adaptation to the eccentric
      contractions known to normally occur during eye movements. Furthermore, a number
      of changes are seen that closely relate to the unique nature of extraocular
      muscle.

PMID- 17229716
TI  - Employment status and frequent mental distress among adults with disabilities.
AB  - BACKGROUND: It has been postulated that poor mental health can lead to disability
      and disability can lead to unemployment. However, the association between poor
      mental health and employment status among adults with disabilities has not been
      well characterized in population-based studies. AIM: To examine the association
      between employment status and frequent mental distress (FMD; 14 or more mentally
      unhealthy days during the previous 30 days) among adults with disabilities.
      METHODS: Cross-sectional data were analysed for 47,377 community-dwelling US
      adults aged 25-64 years with disabilities that participated in the 2001 and 2003
      Behavioural Risk Factor Surveillance System. Logistic regression analysis was
      applied. RESULTS: Among adults with disabilities, the unadjusted prevalence of
      FMD was 18% (SE 0.4) among those employed, 40% (SE 1.3) among those unemployed
      and 44% (SE 0.8) among those unable to work. After adjustments were made for age,
      sex and race/ethnicity, the results indicated that adults with disabilities who
      were unemployed or unable to work were significantly more likely than those
      employed to have FMD (adjusted prevalence: 39 and 45%, respectively, versus 18%;
      P < 0.001). These associations persisted after further adjusting for education,
      marital status, health risk behaviours, body mass index, health care coverage and
      self-rated general health (34 and 36%, respectively, versus 19%; P < 0.001).
      CONCLUSION: These findings demonstrate the need for research and development of
      public health interventions to reduce the toll of mental distress among all
      adults with disabilities.

PMID- 17229717
TI  - A cohort mortality and cancer incidence survey of recent entrants (1982-91) to
      the UK rubber industry: findings for 1983-2004.
AB  - AIM: To monitor the occurrence of cancer in a recently defined cohort of UK
      rubber workers. METHODS: A cohort of 8651 male and female workers from 41 UK
      rubber factories has been enumerated. All employees had a minimum of 12 months
      employment and were first employed at one of the participating factories in the
      period 1982-91. Mortality and cancer incidence data for the period 1983-2004 were
      compared with expected values based on appropriate national rates. RESULTS:
      Mortality from lung cancer was close to expectation for males [observed 22,
      standardized mortality ratio (SMR) 93] and females (observed 2, SMR 70).
      Mortality from stomach cancer was also unexceptional in males (observed 4, SMR
      86) and females (observed 0, SMR 0). Although based on small numbers,
      significantly elevated mortality was shown for multiple myeloma in males
      (observed 5, SMR 385) and females (observed 2, SMR 952). All seven of these
      latter deaths occurred in workers from the general rubber goods (GRG) sector.
      CONCLUSIONS: The findings should be treated with caution as they relate to a
      relatively early period of follow-up. Nevertheless, they hold out the prospect
      that the elevated SMRs for stomach and lung cancers reported for historical
      cohorts of UK rubber workers will not be present in more recent cohorts. The
      elevated occurrence of multiple myeloma may represent no more than a chance
      finding. Alternatively, these findings may reflect the presence of an
      unrecognized occupational cancer hazard in parts of the GRG sector of the UK
      rubber industry.

PMID- 17229718
TI  - What determines the size of occupational health services in UK universities?
AB  - BACKGROUND: There is wide, largely unexplained, variation in occupational health
      (OH) provision between UK employers. AIM: To explain the variation in OH
      provision across the UK university sector. METHODS: Analyses of data from a
      survey of university OH services and from the Higher Education Statistics Agency.
      The outcome variable was clinical (doctor + nurse) staffing of the university's
      OH service. The explanatory variables examined were university size, income,
      research activity score and presence or absence of academic disciplines
      categorized by an expert panel as requiring a high level of OH provision.
      RESULTS: All 117 UK universities were included and 93 (79%) responded; with
      exclusions and incomplete data, between 80 and 89 were included in analyses.
      There was wide variation in clinical OH staffing (range 0-8.4 full-time
      equivalents). Number of university staff explained 34% of the variation in OH
      staffing. After adjusting for other factors, neither the research activity nor
      the presence of high-needs disciplines appeared to be factors currently used by
      employers to determine their investment in OH. CONCLUSIONS: Government or other
      guidelines for university employers should take organizational size into account.
      Employers may need guidance on how to provide OH services proportionate to
      specific occupational hazards or other OH needs.

PMID- 17229719
TI  - Occupational health provision in UK universities.
AB  - BACKGROUND: Very few studies have been done of occupational health provision
      across an entire employment sector and universities are particularly
      understudied. The British government published updated guidance on university
      occupational health in 2006. AIM: To describe the occupational health services to
      all the universities in the UK. METHODS: All 117 universities in the UK were
      included. Detailed surveys were carried out in 2002, 2003 and 2004 requesting
      self-completed information from each university occupational health service. This
      paper presents information on general characteristics of the service, staffing,
      services provided and outcome reporting. RESULTS: There was variation in the type
      of occupational health provision; half the universities had an in-house
      occupational health service, 32% used a contractor, 9% relied on the campus
      primary care or student health service and 9% had ad hoc or no arrangements. In
      all, 93 of the 117 (79%) universities responded to the detailed questionnaire,
      the response rate being higher from in-house services and from larger
      universities. There was a wide variation in staffing levels but the average
      service was small, staffed by one full-time nurse with one half-day of doctor
      time per week and a part-time clerical or administrative member of staff. A range
      of services was provided but, again, there was wide variation between
      universities. CONCLUSIONS: It is unclear if the occupational health provision to
      universities is proportional to their needs. The wide variation suggests that
      some universities may have less adequate services than others.

PMID- 17229720
TI  - Vocational rehabilitation of locomotive engineers with ischaemic heart disease.
AB  - BACKGROUND: There is resistance among railway companies and their occupational
      health services to rehabilitating locomotive engineers with ischaemic heart
      disease to their former driving work. AIM: To study the outcome of vocational
      rehabilitation for locomotive engineers with ischaemic heart disease. METHODS: In
      seven European countries, selected locomotive engineers with ischaemic heart
      disease were compared to a matched group of healthy engineers. At the end of each
      calendar year between 1990 and 1999, questionnaires were completed by local
      occupational health physicians to provide information on accidents, incidents
      (professional mistakes), sick leave, (recurrent) cardiac events, death and early
      retirement. We used the life table method with five follow-up years to calculate
      the risk of accidents, incidents and recurrent cardiac events. RESULTS: The
      accident rate for the cardiac group was 3.8 accidents per 100 person-years, as
      compared to a rate of 6.0 in the reference group. The rates for incidents were
      0.9 and 2.0, respectively. Neither of these differences were statistically
      significant. The duration of sick leave was significantly longer among the
      cardiac group than it was among the reference group, but only in the first follow
      up year. Thirteen recurrent cardiac events occurred in the cardiac group, as
      compared to a single cardiac event in the reference group. There was no
      difference in the proportion of retirement cases. One engineer in each of the two
      groups died of cardiac disease. CONCLUSIONS: Locomotive engineers can safely
      resume driving duties following onset of cardiac disease.

PMID- 17229721
TI  - Inequality in the health status of workers in small-scale enterprises.
AB  - BACKGROUND: Small-scale enterprises (SSEs) usually share poorer resources for
      promoting occupational health. AIM: To investigate inequality of health status
      among SSEs in Japan. METHOD: A cross-sectional, multiple-centred study was
      carried out using the periodical health check-up data for the fiscal year 2000 to
      compare the age-adjusted proportions of workers with hypertension (HT),
      hyperlipidaemia, impaired glucose tolerance (IGT) and obesity and of current
      smokers by size of enterprise, i.e. <or=29, 30-49, 50-99, 100-299, 300-999 and
      >or=1000 employees in Japan. RESULTS: From five leading occupational health
      organizations, data were collected for 9833 enterprises with a total of 436 729
      subjects, 302 383 males and 134 346 females. The proportions of workers in SSEs
      with <or=49 employees with HT, IGT and obesity were 8.5, 5.0 and 3.5%,
      respectively, higher than those in enterprises with >or=50 male employees. The
      prevalence of smokers in SSEs with <or=49 employees was 61%, 2-6% higher than in
      enterprises with >or=50 male employees. These proportions showed a significantly
      increasing tendency with decreasing size of male workforce. CONCLUSION: Despite
      the cross-sectional design and only adjusting age as a potential confounder,
      higher proportions of HT, IGT, obesity and smoking in male workers were found in
      SSEs compared to larger organizations.

PMID- 17229722
TI  - MT1-MMP down-regulates the glucose 6-phosphate transporter expression in marrow
      stromal cells: a molecular link between pro-MMP-2 activation, chemotaxis, and
      cell survival.
AB  - Bone marrow-derived stromal cells (BMSC) are avidly recruited by experimental
      vascularizing tumors, which implies that they must respond to tumor-derived
      growth factor cues. In fact, BMSC chemotaxis and cell survival are regulated, in
      part, by the membrane type-1 matrix metalloproteinase (MT1-MMP), an MMP also
      involved in pro-MMP-2 activation and in degradation of the extracellular matrix
      (ECM). Given that impaired chemotaxis was recently observed in bone marrow cells
      isolated from a glucose 6-phosphate transporter-deficient (G6PT-/-) mouse model,
      we sought to investigate the potential MT1-MMP/G6PT signaling axis in BMSC. We
      show that MT1-MMP-mediated activation of pro-MMP-2 by concanavalin A (ConA)
      correlated with an increase in the sub-G1 cell cycle phase as well as with cell
      necrosis, indicative of a decrease in BMSC survival. BMSC isolated from Egr-1-/-
      mouse or MT1-MMP gene silencing in BMSC with small interfering RNA (siMT1-MMP)
      antagonized both the ConA-mediated activation of pro-MMP-2 and the induction of
      cell necrosis. Overexpression of recombinant full-length MT1-MMP triggered
      necrosis and this was signaled through the cytoplasmic domain of MT1-MMP. ConA
      inhibited both the gene and protein expression of G6PT, while overexpression of
      recombinant G6PT inhibited MT1-MMP-mediated pro-MMP-2 activation but could not
      rescue BMSC from ConA-induced cell necrosis. Cell chemotaxis in response to the
      tumorigenic growth factor sphingosine 1-phosphate was significantly abrogated in
      siMT1-MMP BMSC and in chlorogenic acid-treated BMSC. Altogether, we provide
      evidence for an MT1-MMP/G6PT signaling axis that regulates BMSC survival, ECM
      degradation, and mobilization. This may lead to optimized clinical applications
      that use BMSC as a platform for the systemic delivery of therapeutic or anti
      cancer recombinant proteins in vivo.

PMID- 17229723
TI  - Nitrosative stress inhibits the aminophospholipid translocase resulting in
      phosphatidylserine externalization and macrophage engulfment: implications for
      the resolution of inflammation.
AB  - Macrophage recognition of apoptotic cells depends on externalization of
      phosphatidylserine (PS), which is normally maintained within the cytosolic
      leaflet of the plasma membrane by aminophospholipid translocase (APLT). APLT is
      sensitive to redox modifications of its -SH groups. Because activated macrophages
      produce reactive oxygen and nitrogen species, we hypothesized that macrophages
      can directly participate in apoptotic cell clearance by S-nitrosylation/oxidation
      and inhibition of APLT causing PS externalization. Here we report that exposure
      of target HL-60 cells to nitrosative stress inhibited APLT, induced PS
      externalization, and enhanced recognition and elimination of "nitrosatively"
      modified cells by RAW 264.7 macrophages. Using S-nitroso-L-cysteine-ethyl ester
      (SNCEE) and S-nitrosoglutathione (GSNO) that cause intracellular and
      extracellular trans-nitrosylation of proteins, respectively, we found that SNCEE
      (but not GSNO) caused significant S-nitrosylation/oxidation of thiols in HL-60
      cells. SNCEE also strongly inhibited APLT, activated scramblase, and caused PS
      externalization. However, SNCEE did not induce caspase activation or nuclear
      condensation/fragmentation suggesting that PS externalization was dissociated
      from the common apoptotic pathway. Dithiothreitol reversed SNCEE-induced S
      nitrosylation, APLT inhibition, and PS externalization. SNCEE but not GSNO
      stimulated phagocytosis of HL-60 cells. Moreover, phagocytosis of target cells by
      lipopolysaccharide-stimulated macrophages was significantly suppressed by an NO.
      scavenger, DAF-2. Thus, macrophage-induced nitrosylation/oxidation plays an
      important role in cell clearance, and hence in the resolution of inflammation.

PMID- 17229724
TI  - Contrasting behavior of higher plant photosystem I and II antenna systems during
      acclimation.
AB  - In this work we analyzed the photosynthetic apparatus in Arabidopsis thaliana
      plants acclimated to different light intensity and temperature conditions. Plants
      showed the ability to acclimate into different environments and avoid
      photoinhibition. When grown in high light, plants had a faster activation rate
      for energy dissipation (qE). This ability was correlated to higher accumulation
      levels of a specific photosystem II subunit, PsbS. The photosystem II antenna
      size was also regulated according to light exposure; smaller antenna size was
      observed in high light-acclimated plants with respect to low light plants.
      Different antenna polypeptides did not behave similarly, and Lhcb1, Lchb2, and
      Lhcb6 (CP24) are shown to undergo major levels of regulation, whereas Lhcb4 and
      Lhcb5 (CP29 and CP26) maintained their stoichiometry with respect to the reaction
      center in all growth conditions. The effect of acclimation on photosystem I
      antenna was different; in fact, the stoichiometry of any Lhca antenna proteins
      with respect to photosystem I core complex was not affected by growth conditions.
      Despite this stability in antenna stoichiometry, photosystem I light harvesting
      function was shown to be regulated through different mechanisms like the control
      of photosystem I to photosystem II ratio and the association or dissociation of
      Lhcb polypeptides to photosystem I.

PMID- 17229725
TI  - Paraquat increases cyanide-insensitive respiration in murine lung epithelial
      cells by activating an NAD(P)H:paraquat oxidoreductase: identification of the
      enzyme as thioredoxin reductase.
AB  - Pulmonary fibrosis is one of the most severe consequences of exposure to
      paraquat, an herbicide that causes rapid alveolar inflammation and epithelial
      cell damage. Paraquat is known to induce toxicity in cells by stimulating oxygen
      utilization via redox cycling and the generation of reactive oxygen
      intermediates. However, the enzymatic activity mediating this reaction in lung
      cells is not completely understood. Using self-referencing microsensors, we
      measured the effects of paraquat on oxygen flux into murine lung epithelial
      cells. Paraquat (10-100 microm) was found to cause a 2-4-fold increase in
      cellular oxygen flux. The mitochondrial poisons cyanide, rotenone, and antimycin
      A prevented mitochondrial- but not paraquat-mediated oxygen flux into cells. In
      contrast, diphenyleneiodonium (10 microm), an NADPH oxidase inhibitor, blocked
      the effects of paraquat without altering mitochondrial respiration. NADPH
      oxidases, enzymes that are highly expressed in lung epithelial cells, utilize
      molecular oxygen to generate superoxide anion. We discovered that lung epithelial
      cells possess a distinct cytoplasmic diphenyleneiodonium-sensitive
      NAD(P)H:paraquat oxidoreductase. This enzyme utilizes oxygen, requires NADH or
      NADPH, and readily generates the reduced paraquat radical. Purification and
      sequence analysis identified this enzyme activity as thioredoxin reductase.
      Purified paraquat reductase from the cells contained thioredoxin reductase
      activity, and purified rat liver thioredoxin reductase or recombinant enzyme
      possessed paraquat reductase activity. Reactive oxygen intermediates and
      subsequent oxidative stress generated from this enzyme are likely to contribute
      to paraquat-induced lung toxicity.

PMID- 17229726
TI  - Association of protein biogenesis factors at the yeast ribosomal tunnel exit is
      affected by the translational status and nascent polypeptide sequence.
AB  - Ribosome-associated protein biogenesis factors (RPBs) act during a short but
      critical period of protein biogenesis. The action of RPBs starts as soon as a
      nascent polypeptide becomes accessible from the outside of the ribosome and ends
      upon termination of translation. In yeast, RPBs include the chaperones Ssb1/2 and
      ribosome-associated complex, signal recognition particle, nascent polypeptide
      associated complex (NAC), the aminopeptidases Map1 and Map2, and the Nalpha
      terminal acetyltransferase NatA. Here, we provide the first comprehensive
      analysis of RPB binding at the yeast ribosomal tunnel exit as a function of
      translational status and polypeptide sequence. We measured the ratios of RPBs to
      ribosomes in yeast cells and determined RPB occupation of translating and non
      translating ribosomes. The combined results imply a requirement for dynamic and
      coordinated interactions at the tunnel exit. Exclusively, NAC was associated with
      the majority of ribosomes regardless of their translational status. All other
      RPBs occupied only ribosomal subpopulations, binding with increased apparent
      affinity to randomly translating ribosomes as compared with non-translating ones.
      Analysis of RPB interaction with homogenous ribosome populations engaged in the
      translation of specific nascent polypeptides revealed that the affinities of
      Ssb1/2, NAC, and, as expected, signal recognition particle, were influenced by
      the amino acid sequence of the nascent polypeptide. Complementary cross-linking
      data suggest that not only affinity of RPBs to the ribosome but also positioning
      can be influenced in a nascent polypeptide-dependent manner.

PMID- 17229727
TI  - Crystal structures of an ATP-dependent hexokinase with broad substrate
      specificity from the hyperthermophilic archaeon Sulfolobus tokodaii.
AB  - Hexokinase catalyzes the phosphorylation of glucose to glucose 6-phosphate by
      using ATP as a phosphoryl donor. Recently, we identified and characterized an ATP
      dependent hexokinase (StHK) from the hyperthermophilic archaeon Sulfolobus
      tokodaii, which can phosphorylate a broad range of sugar substrates, including
      glucose, mannose, glucosamine, and N-acetylglucosamine. Here we present the
      crystal structures of StHK in four different forms: (i) apo-form, (ii) binary
      complex with glucose, (iii) binary complex with ADP, and (iv) quaternary complex
      with xylose, Mg(2+), and ADP. Forms i and iii are in the open state, and forms ii
      and iv are in the closed state, indicating that sugar binding induces a large
      conformational change, whereas ADP binding does not. The four different crystal
      structures of the same enzyme provide "snapshots" of the conformational changes
      during the catalytic cycle. StHK exhibits a core fold characteristic of the
      hexokinase family, but the structures of several loop regions responsible for
      substrate binding are significantly different from those of other known
      hexokinase family members. Structural comparison of StHK with human N
      acetylglucosamine kinase and other hexokinases provides an explanation for the
      ability of StHK to phosphorylate both glucose and N-acetylglucosamine. A Mg(2+)
      ion and coordinating water molecules are well defined in the electron density of
      the quaternary complex structure. This structure represents the first direct
      visualization of the binding mode for magnesium to hexokinase and thus allows for
      a better understanding of the catalytic mechanism proposed for the entire
      hexokinase family.

PMID- 17229728
TI  - Distant N- and C-terminal domains are required for intrinsic kinase activity of
      SMG-1, a critical component of nonsense-mediated mRNA decay.
AB  - Phosphatidylinositol 3-kinase-related kinases (PIKKs) consisting of SMG-1, ATM,
      ATR, DNA-PKcs, and mTOR are a family of proteins involved in the surveillance of
      gene expression in eukaryotic cells. They are involved in mechanisms responsible
      for genome stability, mRNA quality, and translation. They share a large N
      terminal domain and a C-terminal FATC domain in addition to the unique
      serine/threonine protein kinase (PIKK) domain that is different from classical
      protein kinases. However, structure-function relationships of PIKKs remain
      unclear. Here we have focused on one of the PIKK members, SMG-1, which is
      involved in RNA surveillance, termed nonsense-mediated mRNA decay (NMD), to
      analyze the roles of conserved and SMG-1-specific sequences on the intrinsic
      kinase activity. Analyses of sets of point and deletion mutants of SMG-1 in a
      purified system and intact cells revealed that the long N-terminal region and the
      conserved leucine in the FATC domain were essential for SMG-1 kinase activity.
      However, the conserved tryptophan in the TOR SMG-1 (TS) homology domain and the
      FATC domain was not. In addition, the long insertion region between PIKK and FATC
      domains was not essential for SMG-1 kinase activity. These results indicated an
      unexpected feature of SMG-1, i.e. that distantly located N- and C-terminal
      sequences were essential for the intrinsic kinase activity.

PMID- 17229729
TI  - Methylglyoxal inhibits the binding step of collagen phagocytosis.
AB  - Bacterial infection-induced fibrosis affects a wide variety of tissues, including
      the periodontium, but the mechanisms that dysregulate matrix turnover and mediate
      fibrosis are not defined. Since collagen turnover by phagocytosis is an important
      pathway for matrix remodeling, we studied the effect of the bacterial and
      eukaryotic cell metabolite, methylglyoxal (MGO), on the binding step of
      phagocytosis by periodontal fibroblasts. Type 1 collagen was treated with various
      concentrations of methylglyoxal, an important glucose metabolite that modifies
      Arg and Lys residues. The extent of MGO-induced modifications was authenticated
      by amino acid analysis, solubility, and cross-linking. Cells were incubated with
      fluorescent beads coated with collagen, and the percentage of phagocytic cells
      was estimated by flow cytometry. MGO inhibited collagen binding (20% of control
      for 10 mm MGO) in a time- and concentration-dependent manner. MGO-induced
      inhibition of binding was prevented by aminoguanidine, which blocks the formation
      of collagen cross-links. MGO reduced collagen binding strength and blocked
      intracellular calcium signaling. MGO modified the Arg residue in the critical
      alpha2beta1 integrin-binding recognition sequence of triple helical collagen
      peptides, whereas MGO-induced cross-linking of Lys residues played only a small
      role in binding inhibition. Thus, MGO modifications of Arg residues in collagen
      could be a key factor in the impaired degradation of collagen that promotes
      fibrosis in chronic infections, such as periodontitis.

PMID- 17229730
TI  - Oxygen metabolism by neuronal nitric-oxide synthase.
AB  - Nitric-oxide synthases (NOS) catalyze nitric oxide (NO) formation from the amino
      acid L-arginine. NOS is known to catalyze more than one reaction: the NO
      producing reaction is considered to be the coupled reaction, and the uncoupled
      reactions are those that produce reactive (reduced) oxygen species (ROS), such as
      superoxide anion (O-2.) and/or hydrogen peroxide (H2O2). As an oxygenase, NOS has
      been known for more than two decades, yet there is no complete description of
      oxygen stoichiometry. The present paper is focused on oxygen stoichiometry and
      the effects of cofactor binding on the neuronal isoform (nNOS) on oxygen uptake
      and product formation. Products of the uncoupled reactions are analyzed using
      diacetyldeuteroheme-substituted horseradish peroxidase as a trapping agent for
      both O-2. and H2O2. The addition of calmodulin not only stimulated the oxygen
      uptake rate but also changed the product of the uncoupled reaction, supporting
      the possibility of two different sites for electron leakage to molecular oxygen.
      Quantitative analysis of the uncoupled (substrate-free) reaction revealed a
      stoichiometry close to the theoretical value, and adding L-arginine not only
      initiates the coupled reaction, but also inhibits oxygen uptake. The presence of
      tetrahydrobiopterin affects oxygen metabolism by lowering the apparent Km value
      of nNOS for oxygen in the uncoupled reaction.

PMID- 17229731
TI  - Cu(I) binding and transfer by the N terminus of the Wilson disease protein.
AB  - Wilson and Menkes diseases are genetic disorders of copper metabolism caused by
      mutations in the Wilson (WND) and Menkes (MNK) copper-transporting P1B-type
      ATPases. The N termini of these ATPases consist of six metal binding domains
      (MBDs). The MBDs interact with the copper chaperone Atox1 and are believed to
      play roles in catalysis and in copper-mediated cellular relocalization of WND and
      MNK. Although all six MBDs have similar folds and bind one Cu(I) ion via a
      conserved CXXC motif, biochemical and genetic data suggest that they have
      distinct functions. Most studies aimed at characterizing the MBDs have employed
      smaller polypeptides consisting of one or two domains. The role of each MBD is
      probably defined by its environment within the six-domain N terminus, however. To
      study the properties of the individual domains within the context of the intact
      Wilson N terminus (N-WND), a series of variants in which five of the six metal
      binding CXXC motifs are mutated to SXXS was generated. For each variant, the
      Cu(I) binding affinity and the ability to exchange Cu(I) with Atox1 were
      investigated. The results indicate that Atox1 can deliver Cu(I) to and remove
      Cu(I) from each MBD, that each MBD has stronger Cu(I) retention properties than
      Atox1, and that all of the MBDs as well as Atox1 have similar K(Cu) values of
      (2.2-6.3) x 10(10) m(-1). Therefore, the specific role of each MBD is not
      conferred by its position within the intact N-WND but may be related to
      interactions with other domains and partner proteins.

PMID- 17229732
TI  - Differential effects of arginine methylation on RBP16 mRNA binding, guide RNA
      (gRNA) binding, and gRNA-containing ribonucleoprotein complex (gRNP) formation.
AB  - Mitochondrial gene expression in Trypanosoma brucei involves the coordination of
      multiple events including polycistronic transcript cleavage, polyadenylation, RNA
      stability, and RNA editing. Arg methylation of RNA binding proteins has the
      potential to influence many of these processes via regulation of protein-protein
      and protein-RNA interactions. Here we demonstrate that Arg methylation
      differentially regulates the RNA binding capacity and macromolecular interactions
      of the mitochondrial gene regulatory protein, RBP16. We show that, in T. brucei
      mitochondria, RBP16 forms two major stable complexes: a 5 S multiprotein complex
      and an 11 S complex consisting of the 5 S complex associated with guide RNA
      (gRNA). Expression of a non-methylatable RBP16 mutant protein demonstrates that
      Arg methylation of RBP16 is required to maintain the protein-protein interactions
      necessary for assembly and/or stability of both complexes. Down-regulation of the
      major trypanosome type 1 protein arginine methyltransferase, TbPRMT1, disrupts
      formation of both the 5 and 11 S complexes, indicating that TbPRMT1-catalyzed
      methylation of RBP16 Arg-78 and Arg-85 is critical for complex formation. We also
      show that Arg methylation decreases the capacity of RBP16 to associate with gRNA.
      This is not a general effect on RBP16 RNA binding, however, since methylation
      conversely increases the association of the protein with mRNA. Thus, TbPRMT1
      catalyzed Arg methylation has distinct effects on RBP16 gRNA and mRNA association
      and gRNA-containing ribonucleoprotein complex (gRNP) formation.

PMID- 17229733
TI  - SMAR1-derived P44 peptide retains its tumor suppressor function through
      modulation of p53.
AB  - The use of pharmacologically active short peptide sequences is a better option in
      cancer therapeutics than the full-length protein. Here we report one such 44-mer
      peptide sequence of SMAR1 (TAT-SMAR1 wild type, P44) that retains the tumor
      suppressor activity of the full-length protein. The protein transduction domain
      of human immunodeficiency virus, type 1, Tat protein was used here to deliver the
      33-mer peptide of SMAR1 into the cells. P44 peptide could efficiently activate
      p53 by mediating its phosphorylation at serine 15, resulting in the activation of
      p21 and in effect regulating cell cycle checkpoint. In vitro phosphorylation
      assays with point-mutated P44-derived peptides suggested that serine 347 of SMAR1
      was indispensable for its activity and represented the substrate motif for the
      protein kinase C family of proteins. Using xenograft nude mice models, we further
      demonstrate that P44 was capable of inhibiting tumor growth by preventing
      cellular proliferation. P44 treatment to tumor-bearing mice prevented the
      formation of poorly organized tumor vasculature and an increase in hypoxia
      inducible factor-1alpha expression, both being signatures of tumor progression.
      The chimeric TAT-SMAR1-derived peptide, P44, thus has a strong therapeutic
      potential as an anticancer drug.

PMID- 17229734
TI  - Crystal structure of Escherichia coli ketopantoate reductase in a ternary complex
      with NADP+ and pantoate bound: substrate recognition, conformational change, and
      cooperativity.
AB  - Ketopantoate reductase (KPR, EC 1.1.1.169) catalyzes the NADPH-dependent
      reduction of ketopantoate to pantoate, an essential step for the biosynthesis of
      pantothenate (vitamin B5). Inhibitors of the enzymes of this pathway have been
      proposed as potential antibiotics or herbicides. Here we present the crystal
      structure of Escherichia coli KPR in a precatalytic ternary complex with NADP+
      and pantoate bound, solved to 2.3 A of resolution. The asymmetric unit contains
      two protein molecules, each in a ternary complex; however, one is in a more
      closed conformation than the other. A hinge bending between the N- and C-terminal
      domains is observed, which triggers the switch of the essential Lys176 to form a
      key hydrogen bond with the C2 hydroxyl of pantoate. Pantoate forms additional
      interactions with conserved residues Ser244, Asn98, and Asn180 and with two
      conservatively varied residues, Asn194 and Asn241. The steady-state kinetics of
      active site mutants R31A, K72A, N98A, K176A, S244A, and E256A implicate Asn98 as
      well as Lys176 and Glu256 in the catalytic mechanism. Isothermal titration
      calorimetry studies with these mutants further demonstrate the importance of
      Ser244 for substrate binding and of Arg31 and Lys72 for cofactor binding. Further
      calorimetric studies show that KPR discriminates binding of ketopantoate against
      pantoate only with NADPH bound. This work provides insights into the roles of
      active site residues and conformational changes in substrate recognition and
      catalysis, leading to the proposal of a detailed molecular mechanism for KPR
      activity.

PMID- 17229735
TI  - Escherichia coli twin arginine (Tat) mutant translocases possessing relaxed
      signal peptide recognition specificities.
AB  - The twin arginine (Tat) secretion pathway allows the translocation of folded
      proteins across the cytoplasmic membrane of bacteria. Tat-specific signal
      peptides contain a characteristic amino acid motif ((S/T)RRXFLK) including two
      highly conserved consecutive arginine residues that are thought to be involved in
      the recognition of the signal peptides by the Tat translocase. Here, we have
      analyzed the specificity of Tat signal peptide recognition by using a genetic
      approach. Replacement of the two arginine residues in a Tat-specific precursor
      protein by lysine-glutamine resulted in an export-defective mutant precursor that
      was no longer accepted by the wild-type translocase. Selection for restored
      export allowed for the isolation of Tat translocases possessing single mutations
      in either the amino-terminal domain of TatB or the first cytosolic domain of
      TatC. The mutant Tat translocases still efficiently accepted the unaltered
      precursor protein, indicating that the substrate specificity of the translocases
      was not strictly changed; rather, the translocases showed an increased tolerance
      toward variations of the amino acids occupying the positions of the twin arginine
      residues in the consensus motif of a Tat signal peptide.

PMID- 17229736
TI  - Multiple WASP-interacting protein recognition motifs are required for a
      functional interaction with N-WASP.
AB  - The WASP-interacting protein (WIP) targets WASP/WAVE proteins through a
      constitutive interaction with an amino-terminal enabled/VASP homology (EVH1)
      domain. Parallel investigations had previously identified two distinct N-WASP
      binding motifs corresponding to WIP residues 451-461 and 461-485, and we
      determined the structure of a complex between WIP-(461-485) and the N-WASP EVH1
      domain (Volkman, B. F., Prehoda, K. E., Scott, J. A., Peterson, F. C., and Lim,
      W. A. (2002) Cell 111, 565-576). The present results show that, when combined,
      the WIP-(451-485) sequence wraps further around the EVH1 domain, extending the
      interface observed previously. Specific contacts with three WIP epitopes
      corresponded to regions of high sequence conservation in the verprolin family. A
      central polyproline motif occupied the canonical binding site but in a reversed
      orientation relative to other EVH1 complexes. This interaction was augmented in
      the amino- and carboxyl-terminal directions by additional hydrophobic contacts
      involving WIP residues 454-459 and 475-478, respectively. Disruption of any of
      the three WIP epitopes reduced N-WASP binding in cells, demonstrating a
      functional requirement for the entire binding domain, which is significantly
      longer than the polyproline motifs recognized by other EVH1 domains.

PMID- 17229737
TI  - Probing the roles of active site residues in the 3'-5' exonuclease of the Werner
      syndrome protein.
AB  - Werner syndrome is a premature aging disease caused by mutations in the WS gene
      and a deficiency in the function of Werner protein (WRN). The lack of WRN results
      in a cellular phenotype of genomic instability. WRN belongs to the RecQ DNA
      helicase family, but unlike other RecQ family members it possesses a functional
      exonuclease domain. We determined the crystal structure of mWRNexo (residues 31
      238) bound to Zn(2+) and the sulfate ion. Compared with the structure of human
      WRNexo (hWRNexo), notable conformational changes were observed in several active
      site residues in an H5-H6 loop and in helices H6 and H7 of mWRNexo, presumably
      because of the presence of sulfate, which mimics the phosphate of substrate DNA.
      In particular, the side chains of Lys(185) and Tyr(206) were reoriented toward
      the Zn(2+) ion, whereas the side chain of Arg(190) pointed away from the active
      site center. Mutational analysis of these conserved residues abolished WRN
      exonuclease activity, suggesting that these residues play a critical role in the
      WRNexo activity. Based on substrate modeling and mutational analyses, we propose
      a mechanism by which WRNexo becomes activated upon substrate DNA binding. We also
      describe the low resolution trimeric structure of mouse WRNexoL (mWRNexoL,
      residues 31-330), as elucidated by small angle x-ray scattering (SAXS) analyses.

PMID- 17229738
TI  - SHP-2 regulates cell growth by controlling the mTOR/S6 kinase 1 pathway.
AB  - Cell growth (accumulation in cell mass) ensues through the promotion of
      macromolecular biosynthesis. S 6 ribosomal kinase 1 (S6K1), which is activated by
      the mammalian target of rapamycin, is critical for cell growth. The early events
      that control S6K1 signaling remain unclear. Here we show that SHP-2 suppresses
      S6K1 activity under conditions of growth factor deprivation. We show that under
      conditions of growth factor deprivation, S6K1 activity was increased in
      fibroblasts lacking functional SHP-2 and in cells where knock down of SHP-2
      expression was established by small interference RNA. Consistent with these
      findings, fibroblasts lacking functional SHP-2 exhibited increased cell size as
      compared with wild type cells. Growth factor deprivation reduces cellular energy,
      and the energy-sensing 5'-AMP-activated protein kinase (AMPK) negatively
      regulates S6K1. We found that SHP-2 promoted AMPK activity under conditions of
      growth factor deprivation (low energy), suggesting that SHP-2 negatively
      regulates S6K1 via an AMPK-dependent pathway. These results implicate SHP-2 as an
      early mediator in the S6K1 signaling pathway to limit cell growth in low energy
      states.

PMID- 17229739
TI  - The xaxAB genes encoding a new apoptotic toxin from the insect pathogen
      Xenorhabdus nematophila are present in plant and human pathogens.
AB  - Xenorhabdus nematophila, a member of the Enterobacteriaceae, kills many species
      of insects by strongly depressing the immune system and colonizing the entire
      body. A peptide cytotoxin has been purified from X. nematophila broth growth, and
      the cytolytic effect on insect immunocytes and hemolytic effect on mammalian red
      blood cells of this toxin have been described (Ribeiro, C., Vignes, M., and
      Brehelin, M. (2003) J. Biol. Chem. 278, 3030-3039). We show here that this toxin,
      Xenorhabdus alpha-xenorhabdolysin (Xax), triggers apoptosis in both insect and
      mammalian cells. We also report the cloning and sequencing of two genes, xaxAB,
      encoding this toxin in X. nematophila. The expression of both genes in
      recombinant Escherichia coli led to the production of active cytotoxin/hemolysin.
      However, hemolytic activity was observed only if the two peptides were added in
      the appropriate order. Furthermore, we report here that inactivation of xaxAB
      genes in X. nematophila abolished the major cytotoxic activity present in broth
      growth, called C1. We also show that these genes are present in various
      entomopathogenic bacteria of the genera Xenorhabdus and Photorhabdus, in
      Pseudomonas entomophila, in the human pathogens Yersinia enterocolitica and
      Proteus mirabilis, and in the plant pathogen Pseudomonas syringae. This toxin
      cannot be classified in any known family of cytotoxins on the basis of amino acid
      sequences, locus organization, and activity features. It is, therefore, probably
      the prototype of a new family of binary toxins.

PMID- 17229740
TI  - Cueing training in persons with Parkinson's disease.

PMID- 17229741
TI  - Steroid-responsive leucoencephalopathy due to cholesterol embolism.

PMID- 17229742
TI  - Transcranial magnetic stimulation and tinnitus: implications for theory and
      practice.

PMID- 17229743
TI  - The inner ear and the neurologist.
AB  - Inner ear disorders are common and patients with vestibular failure often present
      to a neurology clinic because of their dizziness, gait unsteadiness and
      oscillopsia. Vestibular disorders can be divided into peripheral and central
      vestibular disorders. Most of the peripheral vestibular disorders have a clinical
      diagnosis, and a thorough history and examination will often provide a clear
      direction as to the diagnosis. Correct diagnosis allows treatment for many of the
      peripheral and central vestibular disorders. As inner ear damage is generally
      irreversible, early diagnosis allowing prompt treatment is important. The aim of
      this review is to discuss some audiovestibular conditions that may well appear in
      a neurology clinic, and to discuss some recent advances within the
      audiovestibular field that may be of interest to neurologists. Some of the most
      common audiovestibular conditions will be discussed along side more uncommon
      conditions.

PMID- 17229744
TI  - Cueing training in the home improves gait-related mobility in Parkinson's
      disease: the RESCUE trial.
AB  - OBJECTIVES: Gait and mobility problems are difficult to treat in people with
      Parkinson's disease. The Rehabilitation in Parkinson's Disease: Strategies for
      Cueing (RESCUE) trial investigated the effects of a home physiotherapy programme
      based on rhythmical cueing on gait and gait-related activity. METHODS: A single
      blind randomised crossover trial was set up, including 153 patients with
      Parkinson's disease aged between 41 and 80 years and in Hoehn and Yahr stage II
      IV. Subjects allocated to early intervention (n = 76) received a 3-week home
      cueing programme using a prototype cueing device, followed by 3 weeks without
      training. Patients allocated to late intervention (n = 77) underwent the same
      intervention and control period in reverse order. After the initial 6 weeks, both
      groups had a 6-week follow-up without training. Posture and gait scores (PG
      scores) measured at 3, 6 and 12 weeks by blinded testers were the primary outcome
      measure. Secondary outcomes included specific measures on gait, freezing and
      balance, functional activities, quality of life and carer strain. RESULTS: Small
      but significant improvements were found after intervention of 4.2% on the PG
      scores (p = 0.005). Severity of freezing was reduced by 5.5% in freezers only (p
      = 0.007). Gait speed (p = 0.005), step length (p<0.001) and timed balance tests
      (p = 0.003) improved in the full cohort. Other than a greater confidence to carry
      out functional activities (Falls Efficacy Scale, p = 0.04), no carry-over effects
      were observed in functional and quality of life domains. Effects of intervention
      had reduced considerably at 6-week follow-up. CONCLUSIONS: Cueing training in the
      home has specific effects on gait, freezing and balance. The decline in
      effectiveness of intervention effects underscores the need for permanent cueing
      devices and follow-up treatment. Cueing training may be a useful therapeutic
      adjunct to the overall management of gait disturbance in Parkinson's disease.

PMID- 17229745
TI  - Neurological pictures. Chiari I malformation with holocord syrinx.

PMID- 17229746
TI  - Reversible encephalopathy associated with cholesterol embolism syndrome: magnetic
      resonance imaging and pathological findings.
AB  - We describe a patient found to have acute diffuse and reversible encephalopathy
      on magnetic resonance imaging (MRI) associated with cholesterol emboli syndrome
      (CES). The initial MRI showed extensive white matter, basal ganglia and cortical
      damage without evidence of brain infarction. Dramatic clinical and MRI
      improvement was observed with corticosteroids. Pathologically, cholesterol
      crystal emboli were found in the lumen of skin and brain arteries and were
      associated with varying degrees of inflammation of the arteriole wall. This case
      suggests that CES may be responsible for extensive, acute and reversible
      encephalopathy underlined by an inflammation of brain arteries.

PMID- 17229747
TI  - Epilepsy and cerebellar ataxia associated with anti-glutamic acid decarboxylase
      antibodies.
AB  - Anti-glutamic acid decarboxylase (GAD) antibodies are described in stiff-person
      syndrome and also in other neurological syndromes, including cerebellar ataxia
      and epilepsy. This paper reports the case of a patient who had chronic focal
      epilepsy, upbeat nystagmus and cerebellar ataxia, associated with a
      polyautoimmune response including anti-GAD antibodies. Both gait and nystagmus
      improved markedly after immunosuppressive treatment with corticosteroids and
      azathioprine. After the introduction of benzodiazepines, previously refractory
      seizures were completely controlled. Anti-GAD antibodies should be actively
      sought out in pharmacoresistant epilepsy, particularly if other neurological
      abnormalities are present. Combined treatment with immunosuppressants and
      gammahydroxybutyric acidergic agents may be highly effective.

PMID- 17229748
TI  - Johann Bernhard Aloys von Gudden: an outstanding scientist.

PMID- 17229749
TI  - Hashimoto's encephalopathy presenting with progressive cerebellar ataxia.

PMID- 17229750
TI  - Third-nerve palsy heralding dissecting aneurysm of posterior cerebral artery:
      digital subtraction angiography and magnetic resonance appearance.

PMID- 17229751
TI  - Early mitoxantrone-induced cardiotoxicity in secondary progressive multiple
      sclerosis.

PMID- 17229752
TI  - Rasmussen encephalitis with ipsilateral brain stem involvement in an adult
      patient.

PMID- 17229753
TI  - Creutzfeldt-Jakob disease in a Chinese patient with a novel seven extra-repeat
      insertion in PRNP.

PMID- 17229754
TI  - A case of idiopathic musical hallucination with increasing repertoire.

PMID- 17229755
TI  - Paraneoplastic limbic encephalitis associated with potassium channel antibodies:
      value of anti-glial nuclear antibodies in identifying the tumour.

PMID- 17229757
TI  - Protein storage vacuole acidification as a control of storage protein
      mobilization in soybeans.
AB  - Soybean protease C1 (EC 3.4.21.25), the subtilisin-like serine protease that
      initiates the proteolysis of seed storage proteins in germinating soybean
      [Glycine max (L.) Merrill], was localized to the protein storage vacuoles of
      parenchyma cells in the cotyledons by immunoelectron microscopy. This was
      demonstrated not only in germination and early seedling growth as expected, but
      also in two stages of protein storage vacuole development during seed maturation.
      Thus, the plant places the proteolytic enzyme in the same compartment as the
      storage proteins, but is still able to accumulate those protein reserves. Since
      soybean protease C1 activity requires acidic conditions for activity, the
      hypothesis that the pH condition in the protein storage vacuole would support
      protease C1 activity in germination, but not in seed maturation, was tested. As
      hypothesized, acridine orange accumulation in the protein storage vacuole of
      storage parenchyma cells was detected by fluorescence confocal microscopy in
      seedlings before the onset of mobilization of reserve proteins as noted by SDS
      PAGE. Accumulation of the dye was reversed by inclusion of the weak base
      methylamine to dissipate the pH gradient across the vacuolar membrane. Also as
      hypothesized, acridine orange did not accumulate in the protein storage vacuole
      of those parenchyma cells during seed maturation. These results were obtained
      using cells separated by pectolyase treatment and also using cotyledon slices.

PMID- 17229758
TI  - Iron deficiency differently affects metabolic responses in soybean roots.
AB  - Iron deficiency responses were investigated in roots of soybean, a Strategy I
      plant species. Soybean responds to iron deficiency by decreasing growth, both at
      the root and shoot level. Chlorotic symptoms in younger leaves were evident after
      a few days of iron deficiency, with chlorophyll content being dramatically
      decreased. Moreover, several important differences were found as compared with
      other species belonging to the same Strategy I. The main differences are (i) a
      lower capacity to acidify the hydroponic culture medium, that was also reflected
      by a lower H(+)-ATPase activity as determined in a plasma membrane-enriched
      fraction isolated from the roots; (ii) a drastically reduced activity of the
      phosphoenolpyruvate carboxylase enzyme; (iii) a decrease in both cytosolic and
      vacuolar pHs; (iv) an increase in the vacuolar phosphate concentration, and (v)
      an increased exudation of organic carbon, particularly citrate, phenolics, and
      amino acids. Apparently, in soybean roots, some of the responses to iron
      deficiency, such as the acidification of the rhizosphere and other related
      processes, do not occur or occur only at a lower degree. These results suggest
      that the biochemical mechanisms induced by this nutritional disorder are
      differently regulated in this plant. A possible role of inorganic phosphate in
      the balance of intracellular pHs is also discussed.

PMID- 17229759
TI  - Geophysical imaging of root-zone, trunk, and moisture heterogeneity.
AB  - The most significant biotic and abiotic stress agents of water extremity,
      salinity, and infection lead to wood decay and modifications of moisture and ion
      content, and density. This strongly influences the (di-)electrical and mechanical
      properties and justifies the application of geophysical imaging techniques. These
      are less invasive and have high resolution in contrast to classical methods of
      destructive, single-point measurements for inspecting stresses in trees and
      soils. This review presents some in situ and in vivo applications of electric,
      radar, and seismic methods for studying water status and movement in soils,
      roots, and tree trunks. The electrical properties of a root-zone are a
      consequence of their moisture content. Electrical imaging discriminates
      resistive, woody roots from conductive, soft roots. Both types are recognized by
      low radar velocities and high attenuation. Single roots can generate diffraction
      hyperbolas in radargrams. Pedophysical relationships of water content to
      electrical resistivity and radar velocity are established by diverse infiltration
      experiments in the field, laboratory, and in the full-scale 'GeoModel' at Kiel
      University. Subsurface moisture distributions are derived from geophysical
      attribute models. The ring electrode technique around trunks images the growth
      ring structure of concentric resistivity, which is inversely proportional to the
      fluid content. Healthy trees show a central high resistivity within the dry
      heartwood that strongly decreases towards the peripheral wet sapwood. Observed
      structural deviations are caused by infection, decay, shooting, or predominant
      light and/or wind directions. Seismic trunk tomography also differentiates
      between decayed and healthy woods.

PMID- 17229760
TI  - Overexpression of wheat Na+/H+ antiporter TNHX1 and H+-pyrophosphatase TVP1
      improve salt- and drought-stress tolerance in Arabidopsis thaliana plants.
AB  - Transgenic Arabidopsis plants overexpressing the wheat vacuolar Na(+)/H(+)
      antiporter TNHX1 and H(+)-PPase TVP1 are much more resistant to high
      concentrations of NaCl and to water deprivation than the wild-type strains. These
      transgenic plants grow well in the presence of 200 mM NaCl and also under a water
      deprivation regime, while wild-type plants exhibit chlorosis and growth
      inhibition. Leaf area decreased much more in wild-type than in transgenic plants
      subjected to salt or drought stress. The leaf water potential was less negative
      for wild-type than for transgenic plants. This could be due to an enhanced
      osmotic adjustment in the transgenic plants. Moreover, these transgenic plants
      accumulate more Na(+) and K(+) in their leaf tissue than the wild-type plants.
      The toxic effect of Na(+) accumulation in the cytosol is reduced by its
      sequestration into the vacuole. The rate of water loss under drought or salt
      stress was higher in wild-type than transgenic plants. Increased vacuolar solute
      accumulation and water retention could confer the phenotype of salt and drought
      tolerance of the transgenic plants. Overexpression of the isolated genes from
      wheat in Arabidopsis thaliana plants is worthwhile to elucidate the contribution
      of these proteins to the tolerance mechanism to salt and drought. Adopting a
      similar strategy could be one way of developing transgenic staple crops with
      improved tolerance to these important abiotic stresses.

PMID- 17229761
TI  - Expression of T1Rs and gustducin in palatal taste buds of mice.
AB  - The palatal region of the oral cavity in rodents houses 100-300 taste buds and is
      particularly sensitive to sweet and umami compounds; yet, few studies have
      examined the expression patterns of transduction-related molecules in this taste
      field. We investigated the interrelationships between members of the T1R family
      and between each T1R and gustducin in palatal taste buds. Similar to lingual
      taste buds, T1R1 and T1R2 are generally expressed in separate palatal taste
      cells. In contrast to lingual taste buds, however, T1R2 and T1R3-positive palatal
      taste cells almost always coexpress gustducin, suggesting that sweet taste
      transduction in the palate is almost entirely dependent on gustducin. T1R1
      positive palate taste cells coexpress gustducin about half the time, suggesting
      that other G proteins may contribute to the transduction of umami stimuli in this
      taste field.

PMID- 17229762
TI  - Rock drills used in South African mines: a comparative study of noise and
      vibration levels.
AB  - OBJECTIVES: To compare the noise and vibration levels associated with three hand
      held rock drills (pneumatic, hydraulic and electric) currently used in South
      African mines, and a prototype acoustically shielded self-propelled rock drill.
      METHODS: Equivalent A-weighted sound pressure levels were recorded on a
      geometrical grid, using Rion NL-11 and NL-14 sound level meters. Vibration
      measurements were conducted on the pneumatic, hydraulic and electric drills in
      accordance with the ISO5349-1 (2001) international standard on human exposure to
      hand-transmitted vibration, using a Brupsilonel and Kjaer UA0894 hand adaptor.
      PCB Piezo accelerometers were used to measure vibration in three orthogonal
      directions. No vibration measurements were conducted on the self-propelled drill.
      RESULTS: All four drills emitted noise exceeding 85 dB(A). The pneumatic drill
      reached levels of up to 114 dB(A), while the shielded self-propelled drill almost
      complied with the 85 dB(A) 8 h exposure limit. Vibration levels of up to 31 m s(
      2) were recorded. These levels greatly exceed recommended and legislated levels.
      CONCLUSIONS: Significant engineering advances will need to be made in the
      manufacture of rock drills to impact on noise induced hearing loss and hand arm
      vibration syndrome. Isolating the operator from the drill, as for the self
      propelled drill, addresses the problems of both vibration and noise exposure, and
      is a possible direction for future development.

PMID- 17229763
TI  - In situ observations of domain structures and magnetic flux distributions in Mn
      Zn and Ni-Zn ferrites by Lorentz microscopy and electron holography.
AB  - Domain structures and magnetic flux distributions in Mn-Zn and Ni-Zn ferrites are
      investigated by in situ observations with Lorentz microscopy and electron
      holography. In situ Lorentz microscopic observation with the magnetic field
      applied reveals that the domain walls in Mn-Zn ferrite move easily across the
      grain boundary. On the other hand, each grain of Ni-Zn ferrite is magnetized by
      domain wall motion inside the grain. By taking a series of holograms with
      adjustment of the optical axis and astigmatism while the magnetic field is
      applied, we succeeded in observing the change in magnetic flux distribution
      quantitatively. Eventually, it is clarified that magnetization rotation does not
      take place in the magnetization process of Ni-Zn ferrite. The domain wall widths
      delta in Mn-Zn and Ni-Zn ferrites are evaluated to be 73 and 58 nm, respectively.
      Furthermore, through direct observation of the domain structure in Ni-Cu-Zn
      ferrite with Lorentz microscopy, it is found that the grains with size below 1.5
      microm diameter are single domain.

PMID- 17229764
TI  - Notch2, but not Notch1, is required for proximal fate acquisition in the
      mammalian nephron.
AB  - The Notch pathway regulates cell fate determination in numerous developmental
      processes. Here we report that Notch2 acts non-redundantly to control the
      processes of nephron segmentation through an Rbp-J-dependent process. Notch1 and
      Notch2 are detected in the early renal vesicle. Genetic analysis reveals that
      only Notch2 is required for the differentiation of proximal nephron structures
      (podocytes and proximal convoluted tubules) despite the presence of activated
      Notch1 in the nuclei of putative proximal progenitors. The inability of
      endogenous Notch1 to compensate for Notch2 deficiency may reflect sub-threshold
      Notch1 levels in the nucleus. In line with this view, forced expression of a
      gamma-secretase-independent form of Notch1 intracellular domain drives the
      specification of proximal fates where all endogenous, ligand-dependent Notch
      signaling is blocked by a gamma-secretase inhibitor. These results establish
      distinct (non-redundant), instructive roles for Notch receptors in nephron
      segmentation.

PMID- 17229765
TI  - FoxI1e activates ectoderm formation and controls cell position in the Xenopus
      blastula.
AB  - The segregation of the vertebrate embryo into three primary germ layers is one of
      the earliest developmental decisions. In Xenopus, where the process is best
      understood, the endoderm is specified by a vegetally localized transcription
      factor, VegT, which releases nodal signals that specify the adjacent marginal
      zone of the blastula to become mesoderm. However, little is known about how the
      ectoderm becomes specified. In this paper, we show that the forkhead protein
      FoxI1e (also known as Xema) is required at the blastula stage for normal
      formation of both the central nervous system and epidermis, the two early
      derivatives of the ectoderm. In addition, FoxI1e is required to maintain the
      regional identity of the animal cells of the blastula, the cells that are
      precursors of ectodermal structures. In its absence, they lose contact with the
      animal cap, mix with cells of other germ layers and differentiate according to
      their new positions. Because FoxI1e is initially expressed in the animal region
      of the embryo and is rapidly downregulated in the neural plate, its role in
      neural and epidermal gene expression must precede the division of the ectoderm
      into neural and epidermal. The work also shows that FoxI1e plays a role in the
      embryo in the poorly understood process of differential adhesion, which limits
      cell mixing as primary germ layers become specified.

PMID- 17229766
TI  - Convergent extension, planar-cell-polarity signalling and initiation of mouse
      neural tube closure.
AB  - Planar-cell-polarity (PCP) signalling is necessary for initiation of neural tube
      closure in higher vertebrates. In mice with PCP gene mutations, a broad embryonic
      midline prevents the onset of neurulation through wide spacing of the neural
      folds. In order to evaluate the role of convergent extension in this defect, we
      vitally labelled the midline of loop-tail (Lp) embryos mutant for the PCP gene
      Vangl2. Injection of DiI into the node, and electroporation of a GFP expression
      vector into the midline neural plate, revealed defective convergent extension in
      both axial mesoderm and neuroepithelium, before the onset of neurulation.
      Chimeras containing both wild-type and Lp-mutant cells exhibited mainly wild-type
      cells in the midline neural plate and notochordal plate, consistent with a cell
      autonomous disturbance of convergent extension. Inhibitor studies in whole-embryo
      culture demonstrated a requirement for signalling via RhoA-Rho kinase, but not
      jun N-terminal kinase, in convergent extension and the onset of neural tube
      closure. These findings identify a cell-autonomous defect of convergent
      extension, requiring PCP signalling via RhoA-Rho kinase, during the development
      of severe neural tube defects in the mouse.

PMID- 17229767
TI  - Breast angiosarcoma following lumpectomy and radiotherapy for breast cancer: a
      case with short latent period and false negative result on biopsies.

PMID- 17229768
TI  - Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia ('hand
      foot' syndrome).
AB  - Palmar-plantar erythrodysesthesia (PPE), also called hand-foot syndrome or hand
      to-foot syndrome, is a distinctive and relatively frequent dermatologic toxic
      reaction associated with certain chemotherapeutic agents. Pegylated liposomal
      doxorubicin (PLD), a long-circulating formulation of doxorubicin in which
      doxorubicin hydrochloride is encapsulated within pegylated liposomes, is approved
      to treat patients with metastatic breast cancer, advanced ovarian cancer, and
      acquired immunodeficiency syndrome-related Kaposi's sarcoma. The incidence of PPE
      is increased in patients receiving PLD compared with conventional doxorubicin. In
      studies that utilized the currently approved dose of PLD (50 mg/m(2) every 4
      weeks), approximately 50% of all patients receiving PLD experienced PPE, and
      approximately 20% experienced grade 3 PPE. The pathophysiology of PPE, as it
      occurs with any drug with which it is associated, is not well understood. Studies
      evaluating the development of PPE specifically associated with PLD have not fully
      elucidated the mechanism; however, data support the roles of drug excretion in
      sweat and local pressure as contributors. When PPE develops, clinical
      interventions with respect to altering PLD administration include dose reduction,
      less frequent dosing, and ultimately, drug withdrawal with several consequences
      on treatment efficacy. This article will review the available data regarding the
      etiology and potential management strategies of PPE associated with PLD.

PMID- 17229769
TI  - A double-blind placebo-controlled randomized study of Chinese herbal medicine as
      complementary therapy for reduction of chemotherapy-induced toxicity.
AB  - BACKGROUND: Chinese herbal medicine (CHM) is a common complementary therapy used
      by patients with cancer for reduction of chemotherapy-induced toxic effects. This
      study applied the highest standard of clinical trial methodology to examine the
      role of CHM in reducing chemotherapy-induced toxicity, while maintaining a
      tailored approach to therapy. PATIENTS AND METHODS: Patients with early-stage
      breast or colon cancer who required postoperative adjuvant chemotherapy were
      eligible for the study. Enrolled patients were randomly assigned to one of three
      Chinese herbalists who evaluated and prescribed a combination of single-item
      packaged herbal extract granules. Patients received either CHM or placebo
      packages with a corresponding serial number. The placebo package contained
      nontherapeutic herbs with an artificial smell and taste similar to a typical
      herbal tea. The primary end points were hematologic and non-hematologic toxicity
      according to the National Cancer Institute Common Toxicity Criteria Version 2.
      RESULTS: One hundred and twenty patients were accrued at the time of premature
      study termination. Patient characteristics of the two groups were similar. The
      incidence of grade 3/4 anemia, leukopenia, neutropenia, and thrombocytopenia for
      the CHM and placebo groups were 5.4%, 47.3%, 52.7%, and 1.8% and 1.8%, 32.2%,
      44.7%, and 3.6%, respectively (P = 0.27, 0.37, 0.63, and 0.13, respectively).
      Incidence of grade 2 nausea was the only non-hematologic toxicity that was
      significantly reduced in the CHM group (14.6% versus 35.7%, P = 0.04).
      CONCLUSIONS: Traditional CHM does not reduce the hematologic toxicity associated
      with chemotherapy. CHM, however, does have a significant impact on control of
      nausea.

PMID- 17229770
TI  - Is carboplatin-paclitaxel combination the standard treatment of elderly ovarian
      cancer patients?

PMID- 17229771
TI  - Follow-up of successfully treated testicular cancer patients: consequences of the
      metabolic syndrome.

PMID- 17229772
TI  - Venlafaxine is superior to clonidine as treatment of hot flashes in breast cancer
      patients--a double-blind, randomized study.
AB  - BACKGROUND: Classical hormone replacement therapy for hot flashes is
      contraindicated in breast cancer especially in endocrine responsive disease.
      PATIENTS AND METHODS: In a double-blind, randomized phase III study, breast
      cancer patients suffering from hot flashes at least twice a day, who were not
      taking any medication against hypertension and depression received either
      clonidine 0.075 mg twice a day or venlafaxine 37.5 mg twice a day for 4 weeks.
      The primary end point was defined as the frequency of hot flashes after 4 weeks
      of treatment. A self-reported 1-week hot flash and other symptom questionnaire
      were kept before the start of treatment until the end of treatment course.
      RESULTS: From April 2002 to October 2004, 80 patients were recruited of whom 64
      were assessable for efficacy analyses. Thirty-three received clonidine and 31
      venlafaxine, nine patients stopped early because of side-effects and seven
      withdrew consent. At the end of treatment week 4, the median hot flash frequency
      dropped by 7.6 hot flashes per day for patients receiving venlafaxine and 4.85
      hot flashes per day for those receiving clonidine (P = 0.025). CONCLUSION:
      Venlafaxine is significantly more effective in reducing the frequency of hot
      flashes in breast cancer patients than clonidine.

PMID- 17229773
TI  - Trastuzumab: mechanism of action, resistance and future perspectives in HER2
      overexpressing breast cancer.
AB  - Trastuzumab is a humanized mAb directed against the extracellular domain of the
      tyrosine kinase receptor HER2. Trastuzumab has shown clinical activity in HER2
      overexpressing breast cancers and, at present, is currently approved for patients
      whose tumours have this abnormality, in both the metastatic and the adjuvant
      setting. Several issues about its optimal use, however, are still unresolved. One
      of the reasons for these uncertainties lies in the absence of conclusive data
      about its mechanism of action and possible primary or acquired resistance
      mechanisms. Therefore, clinical questions such as how to optimize patient
      selection, how to prevent resistance to trastuzumab, or what is the optimal
      management of those patients whose tumours progress during treatment still await
      convincing answers. This review summarises the current knowledge on the
      preclinical and clinical evidence about the mechanism of action of trastuzumab
      and on the mechanisms underlying the development of resistance and also briefly
      discusses their possible clinical implications.

PMID- 17229774
TI  - The results of consolidation with autologous stem-cell transplantation in
      patients with peripheral T-cell lymphoma (PTCL) in first complete remission: the
      Spanish Lymphoma and Autologous Transplantation Group experience.
AB  - BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of
      aggressive lymphomas associated with poor prognosis with standard chemotherapy.
      Consolidation with autologous stem-cell transplantation (ASCT) may improve
      survival. We present 74 patients transplanted in first complete response (CR)
      from the Spanish Lymphoma and Autologous Transplantation Group cooperative group.
      PATIENTS AND METHODS: Median age was 46 years. Eighty-eight percent presented
      advanced (III-IV) Ann Arbor stage; 53% had B symptoms; 52% had high lactate
      dehydrogenase; 65% had two or three risk factors of the adjusted-International
      Prognostic Index; 58% presented a high Tumor score and in 14% more than two
      adverse factors of the Prognostic Index for peripheral T-cell lymphoma (PIT) were
      observed. RESULTS: With a median follow-up of 67 months from diagnosis, the 5
      year overall survival (OS) was 68% and progression-free survival (PFS) reached
      63%. The multivariate analysis showed that the only factor associated with a
      shorter OS and PFS was the presence of more than two risk factors from the PIT
      risk system. CONCLUSIONS: In a retrospective study with a prolonged follow-up,
      consolidation with ASCT in CR patients who had presented unfavorable prognostic
      factors at diagnosis substantially increased the OS and PFS when compared with
      conventional chemotherapy. The PIT risk system identified 14% of patients without
      benefit from ASCT consolidation. Thus, other innovative therapies are still
      necessary in certain cases.

PMID- 17229775
TI  - Second-line chemotherapy with pemetrexed after gemcitabine failure in patients
      with advanced pancreatic cancer: a multicenter phase II trial.
AB  - BACKGROUND: A standard second-line chemotherapy regimen has yet to be defined for
      patients with gemcitabine (Gem)-refractory advanced pancreatic cancer (PC).
      PATIENTS AND METHODS: In this multicenter phase II trial, patients with
      unresectable or metastatic PC who had progressed on single-agent Gem or a Gem
      containing regimen received pemetrexed 500 mg/m(2) as a 10-min infusion every 3
      weeks until disease progression or occurrence of unacceptable toxicity. The
      primary end point was the 3-month survival rate. RESULTS: A total of 192
      treatment cycles were given to 52 patients. The overall response rate was 3.8%
      (two partial responses); 10 patients (19.2%) experienced stable disease, nine of
      them for >12 weeks. At least one CA 19-9 reduction > or =50% occurred in 12
      patients (23.1%). The 3-month survival rate was 75% (95% confidence interval
      63.2% to 86.8%), the median time to tumor progression was 7 weeks (range 1-62
      weeks) and the median overall survival time was 20 weeks (range 1-84 weeks).
      Grade 3/4 hematological toxic effects included (percent of patients): neutropenia
      (17.3%), thrombocytopenia (5.8%) and anemia (3.8%). The most frequent non
      hematological toxic effects were diarrhea, nausea and stomatitis/pharyngitis
      (23.1% each). CONCLUSION: Pemetrexed is a safe treatment option with moderate
      activity in patients with advanced PC after failure of Gem.

PMID- 17229777
TI  - Iatrogenic stigma in outpatient treatment for Hansen's disease (leprosy) in
      Brazil.
AB  - This paper explores how iatrogenic stigma, or stigma that is produced through a
      patient's encounter with physicians or with biomedicine in general, might emerge
      in outpatient treatment for Hansen's disease, or leprosy. Based on in-depth
      interviews with people affected by Hansen's disease and observations conducted at
      several public health clinics in Rio de Janeiro, Brazil, this research identified
      several aspects of the biomedical encounter that generated or contributed to
      stigma, either felt or enacted. Also noted in the research were positive examples
      of techniques used by physicians and health care workers for minimizing or
      circumventing stigma. The paper touches upon several topics, such as culturally
      mediated responses to medication side effects and communication between health
      care workers and patients, that might be salient or useful for health educators
      and others who are attempting to reduce health-related stigma.

PMID- 17229776
TI  - Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer
      patients receiving cisplatin-based chemotherapy.
AB  - BACKGROUND: Customizing chemotherapy on the basis of chemosentitivity prediction
      may improve outcome in advanced bladder cancer patients. Since DNA damaging
      agents are the cornerstones of therapy, we hypothesized that levels of DNA repair
      genes could predict survival. PATIENTS AND METHODS: Messenger RNA expression
      levels of excision repair cross complementing 1 (ERCC1), breast cancer 1 (BRCA1),
      ribonucleotide reductase subunit M1 (RRM1) and caveolin-1 were determined by RT
      PCR in tumor DNA from 57 advanced and metastatic bladder cancer patients treated
      with either gemcitabine/cisplatin or gemcitabine/cisplatin/paclitaxel (Taxol).
      Levels were correlated with survival, time to disease progression and
      chemotherapy response. RESULTS: Median survival was significantly higher in
      patients with low ERCC1 levels (25.4 versus 15.4 months; P = 0.03) (median follow
      up 19 months). A trend towards longer time to progression was observed in
      patients with tumors expressing low levels of all markers. Levels of RRM1, BRCA1
      and caveolin-1, however, failed to predict the survival and a clear link with
      chemotherapy response could not be established. On multivariate analysis with
      pretreatment prognostic factors, ERCC1 emerged as an independent predictive
      factor for survival. CONCLUSION: The results of the study indicate that ERCC1 may
      predict survival in bladder cancer treated by platinum-based therapy.

PMID- 17229778
TI  - Women's participation in a cervical cancer screening program in northern Peru.
AB  - Cervical cancer is often the most common cancer among women in developing
      countries, yet current screening efforts have not been effective in reducing
      incidence and mortality rates in these settings. In an effort to increase
      knowledge about screening participation in low-resource settings, this study
      sought to identify key factors affecting women's participation in a cervical
      screening program in north central Peru. We studied women who were exposed to
      various health promotion educational activities and compared a total of 156 women
      who sought screening between July 2001 and October 2003 with 155 women who did
      not. Results from logistic regression identified four significant predictors of
      screening: higher relative wealth, knowing other screened women, seeking care
      from a health facility when sick and satisfaction with services at the health
      facility. When we restricted our analysis to women who had experienced screening
      in the past, two additional predictors emerged: having a husband who was
      supportive of screening participation and attending an awareness-raising session.
      These results have important programmatic value for tailoring outreach efforts
      for women and indicate that different strategies may be required to best reach
      women who have never been screened.

PMID- 17229779
TI  - Comparative genetics of potential prezygotic and postzygotic isolating barriers
      in a Lycopersicon species cross.
AB  - I compare the genetic basis of quantitative traits that potentially contribute to
      pre- and postzygotic isolation between the plant species Solanum lycopersicum
      (formerly Lycopersicon esculentum) and Solanum habrochaites (formerly
      Lycopersicon hirsutum), using quantitative trait loci (QTL) mapping in a set of
      near-isogenic lines. Putative prezygotic isolating traits include flower size,
      flower shape, stigma exertion, and inflorescence length, that can influence
      pollinator preferences and/or selfing rates, and therefore gene flow between
      divergent types. Postzygotic isolating traits are hybrid pollen and seed
      sterility. Three substantive results emerge from these analyses. First, the
      genetic basis of floral differentiation appears to be somewhat less complex than
      the genetic basis of postzygotic hybrid sterility, although these differences are
      very modest. Second, there is little evidence that traits for floral
      differentiation are causally or mechanistically associated with hybrid sterility
      traits in this species cross. Third, there is little evidence that hybrid
      sterility QTL are more frequently associated with chromosomal centromeric
      regions, in comparison to floral trait QTL, a prediction of centromeric drive
      models of hybrid sterility. Although genome-wide associations are not evident in
      this analysis, several individual chromosomal regions that contain clusters of
      QTL for both floral and sterility traits, or that indicate hybrid sterility
      effects at centromere locations, warrant further fine-scale investigation.

PMID- 17229780
TI  - Radiation exposure to the population of Europe following the Chernobyl accident.
AB  - On the occasion of the 20th anniversary of the Chernobyl accident an attempt has
      been made to evaluate the impact of the Chernobyl accident on the global burden
      of human cancer in Europe. This required the estimation of radiation doses in
      each of the 40 European countries. Dose estimation was based on the analysis and
      compilation of data either published in the scientific literature or provided by
      local experts. Considerable variability has been observed in exposure levels
      among the European populations. The average individual doses to the thyroid from
      the intake of (131)I for children aged 1 y were found to vary from approximately
      0.01 mGy in Portugal up to 750 mGy in Gomel Oblast (Belarus). Thyroid doses to
      adults were consistently lower than the doses received by young children. The
      average individual effective doses from external exposure and ingestion of long
      lived radiocaesium accrued in the period 1986-2005 varied from approximately 0 in
      Portugal to approximately 10 mSv in Gomel Oblast (Belarus) and Bryansk Oblast
      (Russia). The uncertainties in the dose estimates were subjectively estimated on
      the basis of the availability and reliability of the radiation data that were
      used for dose reconstruction in each country.

PMID- 17229781
TI  - Modification of DNA radiolysis by DNA-binding proteins: structural aspects.
AB  - Formation of specific complexes between proteins and their cognate DNA modulates
      the yields and the location of radiation damage on both partners of the complex.
      The radiolysis of DNA-protein complexes is studied for: (1) the Escherichia coli
      lactose operator-repressor complex, (2) the complex between DNA bearing an
      analogue of an abasic site and the repair protein Fpg of Lactococcus lactis.
      Experimental patterns of DNA damages are presented and compared to predicted
      damage distribution obtained using an improved version of the stochastic model
      RADACK. The same method is used for predicting the location of damages on the
      proteins. At doses lower than a threshold that depends on the system, proteins
      protect their specific binding site on DNA while at high doses, the studied
      complexes are disrupted mainly through protein damage. The loss of binding
      ability is the functional consequence of the amino-acids modification by OH*
      radicals. Many of the most probably damaged amino acids are essential for the DNA
      protein interaction and within a complex are protected by DNA.

PMID- 17229782
TI  - Clustering of double strand break-containing chromosome domains is not inhibited
      by inactivation of major repair proteins.
AB  - For efficient repair of DNA double strand breaks (DSBs) cells rely on a process
      that involves the Mre11/Rad50/Nbs1 complex, which may help to protect non
      repaired DNA ends from separating until they can be rejoined by DNA repair
      proteins. It has been observed that as a secondary effect, this process can lead
      to unintended clustering of multiple, initially separate, DSB-containing
      chromosome domains. This work demonstrates that neither inactivation of the major
      repair proteins XRCC3 and the DNA-dependent protein kinase (DNA-PK) nor
      inhibition of DNA-PK by vanillin influences the aggregation of DSB-containing
      chromosome domains.

PMID- 17229783
TI  - Theoretical modelling of radiolytic damage of free DNA bases and within DNA
      macromolecule.
AB  - The base damages in living cell are the most frequent product of deleterious
      effect of ionizing radiation. Experimental yields of modified bases determined in
      free bases and in the double stranded DNA show significant differences in the
      yields of stable products of radiolytic attack. An attempt to explain these
      differences is made with the help of theoretical calculations. The relative
      probabilities of reactions of the most important radiolytic product, OH(*)
      radical, with individual nucleobases, nucleosides and short DNA oligomers are
      calculated and compared to available experimental yields of base damages.

PMID- 17229784
TI  - Significance of 8-oxoG in the spectrum of DNA damages caused by ionising
      radiation of different quality.
AB  - The yields and composition of DNA damages caused by ionising radiation depends on
      radiation quality. With increasing light energy transfer (LET), the proportion of
      isolated DNA damages with respect to cluster damaged sites decreases. Non-double
      strand break complex damages are induced by gamma radiation in mammalian cells at
      least four times more frequently that prompt DSB. The most important product of
      oxidative damage to DNA bases is 8-oxo-7,8-dihydroguanine (8-oxoG). The modelling
      of DNA damage induced by ionising radiation of different qualities was performed
      to assess frequencies and composition of complex damages containing 8-oxoG. The
      occurrence of clusters containing 8-oxoG increases from 6 to 11% for LET in the
      range 0.4-160 keV microm(-1). Distributions of single strand break (SSB) on
      opposite DNA strand around induced 8-oxoG have similar shape for different
      ionising radiations, but differ in their occurrence in the whole spectrum of DNA
      damages. The most probable configuration is a strand break localised at position
      +/-3 bases from 8-oxoG.

PMID- 17229785
TI  - Radiation damage to DNA-protein specific complexes: estrogen response element
      estrogen receptor complex.
AB  - The exposure of a DNA-protein regulatory complex to ionising radiation induces
      damage to both partner biomolecules and thus can affect its functioning. Our
      study focuses on a complex formed by the estrogen response element (ERE) DNA and
      the recombinant human estrogen receptor alpha (ER), which mediates the signalling
      of female sex hormones, estrogens. The method of native polyacrylamide
      retardation gel electrophoresis is used to study the stability of the complex
      under irradiation by low LET radiation ((60)Co gamma rays) and the ability of the
      separately irradiated partners to form complexes. The relative probabilities of
      ERE DNA strand breakage and base damages as well as the probabilities of damages
      to the ER binding domain are calculated using the Monte Carlo method-based model
      RADACK.

PMID- 17229786
TI  - The RBE issues in ion-beam therapy: conclusions of a joint IAEA/ICRU working
      group regarding quantities and units.
AB  - This paper summarises the conclusions of a working group established jointly by
      the International Atomic Energy Agency (IAEA) and the International Commission on
      Radiation Units and Measurements (ICRU) to address some of the relative
      biological effectiveness (RBE) issues encountered in ion-beam therapy. Special
      emphasis is put on the selection and definition of the involved quantities and
      units. The isoeffective dose, as introduced here for radiation therapy
      applications, is the dose that delivered under reference conditions would produce
      the same clinical effects as the actual treatment in a given system, all other
      conditions being identical. It is expressed in Gy. The reference treatment
      conditions are: photon irradiation, 2 Gy per fraction, 5 daily fractions a week.
      The isoeffective dose D(IsoE) is the product of the physical quantity absorbed
      dose D and a weighting factor W(IsoE). W(IsoE) is an inclusive weighting factor
      that takes into account all factors that could influence the clinical effects
      like dose per fraction, overall time, radiation quality (RQ), biological system
      and effects. The numerical value of W(IsoE) is selected by the radiation-oncology
      team for a given patient (or treatment protocol). It is part of the treatment
      prescription. Evaluation of the influence of RQ on W(IsoE) raises complex
      problems because of the clinically significant RBE variations with biological
      effect (late vs. early) and position in depth in the tissues which is a problem
      specific to ion-beam therapy. Comparison of the isoeffective dose with the
      equivalent dose frequently used in proton- and ion-beam therapy is discussed.

PMID- 17229788
TI  - Changes in injecting practices associated with the use of a medically supervised
      safer injection facility.
AB  - Injection drug users (IDUs) are vulnerable to serious health complications
      resulting from unsafe injection practices. We examined whether the use of a
      supervised safer injection facility (SIF) promoted change in injecting practices
      among a representative sample of 760 IDUs who use a SIF in Vancouver, Canada.
      Consistent SIF use was compared with inconsistent use on a number of self
      reported changes in injecting practice variables. More consistent SIF use is
      associated with positive changes in injecting practices, including less reuse of
      syringes, use of sterile water, swabbing injection sites, cooking/filtering
      drugs, less rushed injections, safe syringe disposal and less public injecting.

PMID- 17229789
TI  - A radiographic analysis of external apical root resorption of maxillary incisors
      during active orthodontic treatment.
AB  - External apical root resorption (EARR) is an undesirable consequence of
      orthodontic treatment. The purpose of this study was to measure the amount of
      EARR and to examine its clinical significance in maxillary incisors, during a 12
      month active treatment period. A further aim was to examine the contribution of
      gender, treatment technique, treatment duration, and extraction of maxillary
      first premolars to EARR. The sample comprised 151 maxillary incisor teeth in 40
      patients (16 males, 24 females) aged 12-22 years, with different malocclusions.
      Standard periapical radiographs, using the long-cone paralleling technique, were
      obtained before and 6 and 12 months after the start of treatment. Quantitative
      measurements for 80 central and 71 lateral maxillary incisors were performed
      separately and corrected for image distortion. Root length reduction was
      calculated in millimetres and in terms of the percentage of the original root
      length. Resorption of more than 1 mm at 12 months of active treatment was
      considered to be clinically significant. On average, the degree of EARR for the
      maxillary central incisors was 0.77 +/- 0.42 and 1.67 +/- 0.64 mm, respectively,
      during the 6- and 12-month follow-up (P < 0.001). For the lateral incisors, the
      degree of EARR was 0.88 +/- 0.51 and 1.79 +/- 0.66 mm, respectively (P < 0.001).
      Clinically significant resorption was found for 74 per cent of the centrals and
      82 per cent of the laterals. No significant correlation was observed between EARR
      and treatment technique. EARR was found to be correlated with gender for the
      lateral incisors. The effect of treatment duration (P < 0.001) and premolar
      extraction (P < 0.001) was statistically significant for both tooth groups.

PMID- 17229790
TI  - An index of orthodontic treatment complexity.
AB  - The aim of the present study was to develop an index specifically for the
      measurement of treatment complexity. Input factors were directly related to
      complexity, and the output was a score measuring the degree of treatment
      complexity. The sample comprised 120 sets of dental casts, 30 for each of the
      four main malocclusion classes. Sixteen orthodontists graded the study casts for
      perceived treatment complexity on a six-point scale and then listed, in order of
      importance, up to three occlusal features which they felt contributed to
      complexity from a pre-determined list. Multiple regression analysis was used to
      derive weightings for each occlusal feature, which would reflect the relevant
      treatment complexity. In order to obtain an overall treatment complexity score
      for each case, weightings were then multiplied by the corresponding occlusal
      feature scores and summed. The relationship between treatment complexity scores
      and perceived complexity was examined using Spearman's ranked correlation
      coefficient. The regression equation explained 49.5 per cent of the variance in
      treatment complexity of the whole sample. Regression analysis on the basis of
      malocclusion produced R (2) values of 90.7 per cent for Class I, 42.6 per cent
      for Class II division 1, 62.3 per cent for Class II division 2, and 79.5 per cent
      for Class III malocclusions. The index of orthodontic treatment complexity (IOTC)
      scores showed a moderate but highly significant association with the
      orthodontists' perceived complexity assessments (rho = 0.42, P = 0.000). The
      proposed IOTC shows sufficient promise to warrant further development.

PMID- 17229791
TI  - "There is such a thing as asking for trouble": taking rapid HIV testing to gay
      venues is fraught with challenges.
AB  - OBJECTIVES: To explore the feasibility and acceptability of offering rapid HIV
      testing to men who have sex with men in gay social venues. METHODS: Qualitative
      study with in-depth interviews and focus group discussions. Interview transcripts
      were analysed for recurrent themes. 24 respondents participated in the study. Six
      gay venue owners, four gay service users and one service provider took part in in
      depth interviews. Focus groups were conducted with eight members of a rapid HIV
      testing clinic staff and five positive gay men. RESULTS: Respondents had strong
      concerns about confidentiality and privacy, and many felt that HIV testing was
      "too serious" an event to be undertaken in social venues. Many also voiced
      concerns about issues relating to post-test support and behaviour, and clinical
      standards. Venue owners also discussed the potential negative impact of HIV
      testing on social venues. CONCLUSION: There are currently substantial barriers to
      offering rapid HIV tests to men who have sex with men in social venues. Further
      work to enhance acceptability must consider ways of increasing the
      confidentiality and professionalism of testing services, designing appropriate
      pre-discussion and post-discussion protocols, evaluating different models of
      service delivery, and considering their cost-effectiveness in relation to
      existing services.

PMID- 17229792
TI  - Healthcare and patient costs of a proactive chlamydia screening programme: the
      Chlamydia Screening Studies project.
AB  - BACKGROUND AND OBJECTIVE: Most economic evaluations of chlamydia screening do not
      include costs incurred by patients. The objective of this study was to estimate
      both the health service and private costs of patients who participated in
      proactive chlamydia screening, using mailed home-collected specimens as part of
      the Chlamydia Screening Studies project. METHODS: Data were collected on the
      administrative costs of the screening study, laboratory time and motion studies
      and patient-cost questionnaire surveys were conducted. The cost for each
      screening invitation and for each accepted offer was estimated. One-way
      sensitivity analysis was conducted to explore the effects of variations in
      patient costs and the number of patients accepting the screening offer. RESULTS:
      The time and costs of processing urine specimens and vulvo-vaginal swabs from
      women using two nucleic acid amplification tests were similar. The total cost per
      screening invitation was 20.37 pounds (95% CI 18.94 pounds to 24.83). This
      included the National Health Service cost per individual screening invitation
      13.55 pounds (95% CI 13.15 pounds to 14.33) and average patient costs of 6.82
      pounds (95% CI 5.48 pounds to 10.22). Administrative costs accounted for 50% of
      the overall cost. CONCLUSIONS: The cost of proactive chlamydia screening is
      comparable to those of opportunistic screening. Results from this study, which is
      the first to collect private patient costs associated with a chlamydia screening
      programme, could be used to inform future policy recommendations and provide
      unique primary cost data for economic evaluations.

PMID- 17229793
TI  - How normalised is HIV care in the UK? A survey of current practice and opinion.
AB  - OBJECTIVES: The prognosis for individuals infected with HIV has changed
      dramatically over the past 10 years, with patients living longer and requiring
      other specialist services. It is apparent that access of other healthcare
      professionals to clinical information about a patient's HIV care differs between
      centres in the UK. Lack of awareness of an individual's HIV status may compromise
      their clinical care. AIM: To establish current practice and identify the views of
      clinicians caring for patients infected with HIV. METHODS: Lead consultants in
      all genitourinary medicine departments in the UK were invited to complete a
      questionnaire regarding use of combined HIV and hospital notes and ability of
      general practitioners and other hospital specialists to access information about
      individual patient's HIV care. Clinician's opinions on the "normalisation" of HIV
      management were also sought. RESULTS: Combined notes (outpatient and inpatient)
      were used by 12% (16/130) of respondents. The patient's identifying number was
      used to request blood tests in 86%. Of the respondents, 42% had encountered
      difficulties in communication that affected delivery of care for an HIV-positive
      patient. CONCLUSIONS: Centres using combined notes identified a higher frequency
      of communication with other doctors and specialties, suggesting a higher standard
      of care. Physicians involved in HIV care should consider combining patients' HIV
      and hospital notes for improved clinical care.

PMID- 17229794
TI  - The effect of faecal diversion on human ileum.
AB  - BACKGROUND: The use of a loop ileostomy is an effective method in protecting
      pelvic anastomoses. Its use has increased recently, although there is some debate
      as to the routine use of a stoma. Reversal of the ileostomy is associated with a
      significant morbidity, which may be related to impaired function of the bypassed
      distal limb of the ileum. AIM: To investigate the changes that might occur in the
      distal limb after an interval of faecal diversion. METHODS: Full-thickness
      intestinal circular muscle (CM) strips were prepared from excised loop
      ileostomies taken at the time of closure. The study sample was from the distal
      limb and the control from the proximal limb. Contractile activity was measured
      using an organ bath set up to record isometric contraction after stimulation by
      acetylcholine (ACh). Histological sections were assessed for an index of villous
      atrophy, smooth muscle area, and nerve and vessel density. Analysis was with the
      Wilcoxon signed ranks test for paired data and the Mann-Whitney U test for
      unpaired data. RESULTS: Samples were acquired prospectively from 35 consecutive
      patients. The median time between formation and closure of ileostomy was 34
      weeks. Significant reduction was observed in the strength of CM contraction,
      smooth muscle area and median villous index of the distal limb compared with the
      proximal limb. CONCLUSION: Impaired intestinal function has been proposed as a
      contributory factor in the morbidity that may follow closure of loop ileostomy.
      Significant loss of contractility and smooth muscle strength and villous atrophy
      occur in the distal ileal limb after faecal diversion. Methods of preventing
      these changes should be considered.

PMID- 17229795
TI  - G protein-coupled receptor kinase 6 controls chronicity and severity of dextran
      sodium sulphate-induced colitis in mice.
AB  - BACKGROUND: Infiltration of inflammatory cells into the colon plays an important
      role in the onset and course of inflammatory bowel disease. G-protein-coupled
      receptor kinase 6 (GRK6) is an intracellular kinase that regulates the
      sensitivity of certain G-protein-coupled receptors, including those involved in
      the migration of inflammatory cells. Therefore, it is hypothesised that GRK6
      plays a role in determining the course of inflammation. AIM: To analyse the role
      of GRK6 in the course of dextran sodium sulphate (DSS)-induced colitis. METHODS:
      Colitis was induced by administering 1% DSS in drinking water to GRK6(-/-),
      GRK6(+/-) and wild-type (WT) mice for 6 days. The severity of colitis was
      assessed on the basis of clinical signs, colon length and histology. Moreover,
      keratinocyte-derived chemokine (KC) levels, granulocyte infiltration, interleukin
      1beta (IL1beta), CD4, CD8 and forkhead box protein P3 (FoxP3) expression in the
      colon were determined. In addition, regulatory T cell function in WT and GRK6(-/
      ) mice was analysed. The chemotactic response of granulocytes to colon culture
      supernatants was assessed using a transendothelial migration assay. RESULTS: The
      severity of colitis was increased in GRK6(-/-) and GRK6(+/-) mice and was
      accompanied by increased KC levels and increased granulocyte infiltration.
      Moreover, the chemotactic response of GRK6(-/-) granulocytes to supernatants of
      colon cultures was enhanced. Interestingly, the WT mice completely recovered from
      colitis, whereas the GRK6(-/-) and GRK6(+/-) mice developed chronic colitis,
      which was accompanied by increased IL1beta and CD4 expression and decreased FoxP3
      expression. Moreover, regulatory T cell function was impaired in the GRK6(-/-)
      mice. CONCLUSIONS: The intracellular level of GRK6 is an important factor in
      determining the onset, severity and chronicity of DSS-induced colitis.

PMID- 17229796
TI  - Effectiveness of concomitant immunosuppressive therapy in suppressing the
      formation of antibodies to infliximab in Crohn's disease.
AB  - BACKGROUND: Episodic infliximab (IFX) treatment is associated with the formation
      of antibodies to IFX (ATIs) in the majority of patients, which can lead to
      infusion reactions and a shorter duration of response. Concomitant use of
      immunosuppressives (IS) reduces the risk of ATI formation. AIMS AND METHODS: To
      investigate which of the IS-that is, methotrexate (MTX) or azathioprine (AZA)-is
      most effective at reducing the risk of ATI formation, a multicentre cohort of 174
      patients with Crohn's disease, treated with IFX in an on-demand schedule, was
      prospectively studied. Three groups were studied: no IS (n = 59), concomitant MTX
      (n = 50) and concomitant AZA (n = 65). ATI and IFX concentrations were measured
      in a blinded manner at Prometheus Laboratories before and 4 weeks after each
      infusion. RESULTS: ATIs were detected in 55% (96/174) of the patients. The
      concomitant use of IS therapy (AZA or MTX) was associated with a lower incidence
      of ATIs (53/115; 46%) compared with patients not taking concomitant IS therapy
      (43/59; 73%; p<0.001). The incidence of ATIs was not different for the MTX group
      (44%) compared with the AZA group (48%). Patients not taking IS therapy had lower
      IFX levels (median 2.42 microg/ml (interquartile range (IQR) 1-10.8), maximum 21
      microg/ml) 4 weeks after any follow-up infusion than patients taking concomitant
      IS therapy (median 6.45 microg/ml (IQR 3-11.6), maximum 21 microg/ml; p = 0.065),
      but there was no difference between MTX or AZA. In patients who developed
      significant ATIs >8 microg/ml during follow-up, the IFX levels 4 weeks after the
      first infusion were retrospectively found to be significantly lower than in
      patients who did not develop ATIs on follow-up or had inconclusive ATIs.
      CONCLUSION: Concomitant IS therapy reduces ATI formation associated with IFX
      treatment and improves the pharmacokinetics of IFX. There is no difference
      between MTX and AZA in reducing these risks. ATI profoundly influences the
      pharmacokinetics of IFX. The formation of ATIs >8 microg/ml is associated with
      lower serum levels of IFX already at 4 weeks after its first administration.

PMID- 17229797
TI  - Expression of hypoxia-inducible factor-1alpha and the protein products of its
      target genes in diabetic fibrovascular epiretinal membranes.
AB  - AIMS: To investigate the expression of the hypoxia-inducible factor-1alpha (HIF
      1alpha) and the protein products of its target genes vascular endothelial growth
      factor (VEGF), erythropoietin (Epo) and angiopoietins (Angs), and the
      antiangiogenic pigment epithelium-derived factor (PEDF) in proliferative diabetic
      retinopathy (PDR) epiretinal membranes. METHODS: Sixteen membranes were studied
      by immunohistochemical techniques. RESULTS: Vascular endothelial cells expressed
      HIF-1alpha, Ang-2 and VEGF in 15 (93.75%), 6 (37.5%) and 9 (56.25%) membranes,
      respectively. There was no immunoreactivity for Epo, Ang-1 and PEDF. There were
      significant correlations between the number of blood vessels expressing the
      panendothelial marker CD34 and the numbers of blood vessels expressing HIF-1alpha
      (r = 0.554; p = 0.026), Ang-2 (r = 0.830; p<0.001) and VEGF (r = 0.743; p =
      0.001). The numbers of blood vessels expressing Ang-2 and VEGF in active
      membranes were higher than that in inactive membranes (p = 0.015 and 0.028,
      respectively). CONCLUSIONS: HIF-1alpha, Ang-2 and VEGF may play an important role
      in the pathogenesis of PDR. The findings suggest an adverse angiogenic milieu in
      PDR epiretinal membranes favouring aberrant neovascularisation and endothelial
      abnormalities.

PMID- 17229798
TI  - Pulsed electron avalanche knife: new technology for cataract surgery.
AB  - BACKGROUND: The pulsed electron avalanche knife (PEAK-fc) is a new pulsed
      electrosurgical device that allows for precise, "cold" and traction-free tissue
      dissection. AIM: To evaluate the surgical applicability, safety and potential
      complications of PEAK-fc in complicated cataract surgery. METHODS: The study
      included five children with congenital cataracts, two patients with advanced
      senile cataracts, six adults with mature cataracts, three of them with posterior
      iris synechia, three patients with post-traumatic cataracts with zonulolysis, one
      patient with intumescent traumatic cataract and three patients with massive
      anterior capsule opacification. Anterior and posterior capsulotomies, iris
      synechiolysis, dissection of anterior capsule opacification and fibrotic scar
      tissue were performed. PEAK-fc was set at voltages of 500-700 V, pulse duration
      of 0.1 m and repetition rate of 40-100 Hz. RESULTS: Anterior and posterior
      capsulotomies were successfully and safely performed in all eyes. The edges of
      capsulotomies appeared sharp, showing only limited collateral damage. PEAK-fc
      worked best by just gently touching the capsule, thereby avoiding tractional
      forces or pressure on the lens capsule. Posterior iris synechiae could be
      released and anterior capsule opacification was dissected without complications.
      CONCLUSIONS: PEAK-fc is a very helpful cutting device for complicated cases of
      cataract surgery, especially for mature and congenital cataracts, traumatic
      zonulolysis or anterior segment complications after intraocular inflammation.

PMID- 17229799
TI  - Sub-inner limiting membrane haemorrhage: causes and treatment with vitrectomy.
AB  - BACKGROUND: Preretinal haemorrhages usually occur at the interface between the
      posterior hyaloid and inner limiting membrane (ILM). Less frequently, they are
      located between the ILM and the retinal nerve fibre layer. Sub-ILM haemorrhages
      have been described in a variety of clinical settings and often lead to severe
      visual impairment because of their predilection for the macular region. METHODS:
      A consecutive series of five cases in which sub-ILM haemorrhages were clinically
      suspected and confirmed during early vitrectomy with ILM peeling were reviewed.
      RESULTS: Sub-ILM haemorrhages were clinically suspected in five patients (median
      age 32 years) based on the fundoscopic appearance and clinical setting of
      Terson's syndrome (n = 1), Valsalva retinopathy (n = 2), blood dyscrasia (n = 1)
      and blunt facial trauma (n = 1). Vision was severely impaired in all patients (to
      hand movements in four of five) because of a premacular location of the
      haemorrhage. All patients were treated with early pars plana vitrectomy because
      of insufficient spontaneous visual recovery after a median of 6 weeks. The sub
      ILM location of the haemorrhage could be confirmed intraoperatively in all
      patients by biostaining of the membrane overlying the haemorrhage. ILM peeling
      and aspiration of the haemorrhage resulted in excellent visual recovery in all
      patients. No procedure-related complications were observed. CONCLUSIONS: Sub-ILM
      haemorrhages often occur in a specific clinical context and can lead to severe
      visual impairment in young patients. Given the excellent results and low
      complication rates, timely surgical intervention is justified when spontaneous
      resorption is insufficient.

PMID- 17229800
TI  - Outcome of phacoemulsification in patients with uveitis.
AB  - AIMS: To examine the visual outcome and identify risk factors for postoperative
      uveitis, macular oedema and neodymium-doped yttrium aluminium garnet (Nd:YAG)
      capsulotomy after phacoemulsification and intraocular lens (IOL) implantation in
      patients with uveitis. METHOD: This is a retrospective review of the medical
      records of 101 eyes of 101 patients. One eye was randomly selected for inclusion
      in patients who had bilateral surgery. Patients with juvenile arthritis,
      keratouveitis and lymphoma-associated uveitis were excluded. RESULTS: At the
      first postoperative and final visits, visual acuity was significantly better
      (p<0.001), and 64.4% and 71.3% of patients, respectively, had achieved >or=2
      Snellen's lines of visual improvement. The cumulative probability of doubling of
      the visual angle was 52% over 6 years of follow-up, and this occurred at a higher
      rate in the presence of preoperative retinal or optic nerve lesions (HR (95% CI)
      4.49 (1.41 to 14.29)). Within 3 months after operation, uveitis was more likely
      to develop in female patients (OR (95% CI) 6.21 (1.41 to 27.43)) and in the
      presence of significant intraoperative posterior synechiae (OR (95% CI) 8.43
      (1.09 to 65.41)); macular oedema was more likely to develop in patients who
      developed postoperative uveitis (OR (95% CI) 7.45 (1.63 to 34.16)). Nd:YAG
      capsulotomy occurred at a higher rate in patients aged <or=55 years (HR (95% CI)
      2.28 (1.06, 4.93)) and in those with hydrogel IOLs (HR (95% CI) 3.71 (1.04 to
      13.20)), and occurred at a lower rate in patients who had prophylactic systemic
      corticosteroids (HR (95% CI) 0.25 (0.11 to 0.59)), with plate-haptic silicone
      IOLs (HR (95% CI) 0.23 (0.08 to 0.64)) and three-piece silicone IOLs (HR (95% CI)
      0.19 (0.05 to 0.74)) in comparison to those with polymethylmethacrylate IOLs.
      CONCLUSION: Most patients with uveitis achieve improved visual acuity after
      phacoemulsification, but an increasing rate of visual loss is observed in those
      with pre-existent macular or optic nerve lesions. Identifying patients who are at
      risk of postoperative complications should help in patient counselling and to pre
      empt these complications by using preoperative prophylactic corticosteroids,
      careful IOL selection and postoperative intensive corticosteroids.

PMID- 17229801
TI  - Results of high-density silicone oil as a tamponade agent in macular hole retinal
      detachment in patients with high myopia.
AB  - BACKGROUND: To evaluate the use of high-density silicone oil (HDSO) as a
      tamponade agent for retinal detachment secondary to myopic macular hole. METHODS:
      12 eyes of 12 patients with macular hole retinal detachment underwent pars plana
      vitrectomy, internal limiting membrane peeling and HDSO tamponade. No posturing
      was required postoperatively and HDSO was removed 3-4 months later. Outcome
      measures included macular hole closure and retinal attachment rates, best
      corrected visual acuity (BCVA), and intraoperative and postoperative
      complications. RESULTS: The mean age of the patients was 67.8 years and the mean
      spherical equivalent refractive error was -13.4 diopters. After the removal of
      HDSO, 10 (83%) eyes had macular hole closure with retinal reattachment without
      any tamponade. One eye had retinal reattachment after re-operation and the other
      refused further surgery. At the last follow-up, the median BCVA improved from
      20/800 to 20/600 (p = 0.046). A transient increase in intraocular pressure was
      observed in 5 (42%) eyes and one eye each developed mild oil emulsification and
      transient peripheral choroidal detachment. None of the eyes was found to have
      severe intraocular inflammation postoperatively. CONCLUSIONS: HDSO seemed to be
      an effective tamponade agent for myopic macular hole retinal detachment. Further
      prospective controlled studies seem warranted.

PMID- 17229802
TI  - Quality of life and relative importance: a comparison of time trade-off and
      conjoint analysis methods in patients with age-related macular degeneration.
AB  - AIM: To investigate the relative priorities in quality of life (QoL) in patients
      with age-related macular degeneration (AMD). METHODS: Measures of visual
      function, QoL and utility associated with visual loss were obtained from 122
      patients with AMD classified according to macular morphology. The two methods of
      utility assessment were time trade-off (TTO) and conjoint analysis (CA), which
      have been recommended by the UK's National Institute of Clinical Excellence as
      techniques for the assessment of healthcare priorities. RESULTS: Results show
      that the two methods for assessing utility are poorly related: TTO relates
      moderately to visual function and disease severity but CA does not. CA identified
      two different subgroups of patients: one with outdoor mobility and the other with
      reading as their main priority. CONCLUSION: Further work is needed and caution
      required in interpreting data obtained using these methodologies for determining
      their relative importance in vision-related QoL studies.

PMID- 17229803
TI  - Epidemiology of giant-cell arteritis in an Arab population: a 22-year study.
AB  - OBJECTIVE: To study the epidemiology of biopsy-proven giant-cell arteritis (GCA)
      in an Arab population with clinical features suggestive of GCA. METHODS: Clinical
      records of 102 patients who underwent temporal artery biopsy (TAB) at King Khaled
      Eye Specialist Hospital, Riyadh, Saudi Arabia from January 1983 to December 2004
      were reviewed. RESULTS: Among the 56 men and 46 women who had TAB, 7 (6.8%) had
      biopsy-proven GCA. The mean (SD) age of the biopsy-positive group (71.7 (8.6)
      years) was higher than in the biopsy-negative group (65 (9.8) years; p = 0.005).
      None of the untreated patients with a negative TAB developed additional symptoms
      that are typical of GCA. CONCLUSION: The small absolute number of biopsy-proven
      cases of GCA implies a relatively low incidence of GCA in Arab population,
      confirming previous observations that GCA occurs primarily in the Caucasian
      population.

PMID- 17229804
TI  - Confident complete excision of lid-margin BCCs using a marginal strip: an
      alternative to Mohs' surgery.
AB  - AIMS: To report a new technique of tissue preparation, using a marginal strip,
      after the excision of eyelid basal cell carcinomas (BCCs) and to report the long
      term results of BCCs excised using this technique. METHOD: After the excision of
      eyelid BCC with a safety margin of 4 mm, a 1 mm strip was excised along the whole
      perimeter from the margin of the freshly excised specimen. This marginal strip
      had intact conjunctival mucosa along one edge and skin along the other. The
      marginal strip and the central tumour mass were then fixed immediately in formal
      saline and subjected to conventional histopathology. RESULTS: Of the 61 patients
      who completed a 5 years follow-up, the results of 28 eye-lid BCCs that were
      within 4 mm of the lid margin are reported. The marginal strip was clear in 22
      specimens and had the presence of residual tumour in its margin in 6 specimens.
      These six 6 cases were further managed by observation (n = 2), by further
      surgical excision using marginal strip (n = 2) and by Mohs' surgery (n = 2).
      CONCLUSION: Marginal strip examines the entire resection margins analogous to
      Mohs' technique and we recommend its use in lid margin where tarsus is present
      throughout the specimen and >4 mm from the lid margin.

PMID- 17229805
TI  - Recurrence of choroidal neovascularisation after photodynamic therapy in patients
      with age-related macular degeneration.
AB  - AIM: To determine the incidence of recurrence of choroidal neovascularisation
      (CNV) 18 months after cessation of photodynamic therapy (PDT) with verteporfin
      monotherapy in patients with age-related macular degeneration (AMD). METHODS:
      This was a prospective interventional cohort study. The sample consisted of 108
      individuals with CNV secondary to AMD which was treated with PDT. Data on
      demographics, pre-PDT and post-PDT Early Treatment of Diabetic Retinopathy Study
      (ETDRS) acuity, pre-PDT lesion size and composition were collected for each
      participant. All participants returned for fundus photographs and ETDRS acuity
      measurements 18 months after their final PDT, which were compared with the same
      measurements from the final treatment session to determine recurrence status.
      Recurrences were classified primarily on the basis of haemorrhage and increased
      lesion size. RESULTS: Recurrences were observed in 36 of 108 (33%) eyes. 23 of 36
      (64%) recurrences were clinically meaningful. Of the explanatory variables
      considered, only final PDT acuity was significantly different between those that
      recurred (45.5 ETDRS letters) and those that did not (38.4 letters; p = 0.03).
      CONCLUSION: CNV recurrences are common after PDT for AMD, occurring in 33% of
      eyes in this study. Visual acuity measured at the final PDT treatment visit may
      be a predictor of subsequent recurrence.

PMID- 17229806
TI  - Causes of blindness and visual impairment in Pakistan. The Pakistan national
      blindness and visual impairment survey.
AB  - OBJECTIVE: To determine the causes of blindness and visual impairment in adults
      (> or =30 years old) in Pakistan, and to explore socio-demographic variations in
      cause. METHODS: A multi-stage, stratified, cluster random sampling survey was
      used to select a nationally representative sample of adults. Each subject was
      interviewed, had their visual acuity measured and underwent autorefraction and
      fundus/optic disc examination. Those with a visual acuity of <6/12 in either eye
      underwent a more detailed ophthalmic examination. Causes of visual impairment
      were classified according to the accepted World Health Organization (WHO)
      methodology. An exploration of demographic variables was conducted using
      regression modeling. RESULTS: A sample of 16 507 adults (95.5% of those
      enumerated) was examined. Cataract was the most common cause of blindness (51.5%;
      defined as <3/60 in the better eye on presentation) followed by corneal opacity
      (11.8%), uncorrected aphakia (8.6%) and glaucoma (7.1%). Posterior capsular
      opacification accounted for 3.6% of blindness. Among the moderately visually
      impaired (<6/18 to > or =6/60), refractive error was the most common cause (43%),
      followed by cataract (42%). Refractive error as a cause of severe visual
      impairment/blindness was significantly higher in rural dwellers than in urban
      dwellers (odds ratio (OR) 3.5, 95% CI 1.1 to 11.7). Significant provincial
      differences were also identified. Overall we estimate that 85.5% of causes were
      avoidable and that 904 000 adults in Pakistan have cataract (<6/60) requiring
      surgical intervention. CONCLUSIONS: This comprehensive survey provides reliable
      estimates of the causes of blindness and visual impairment in Pakistan. Despite
      expanded surgical services, cataract still accounts for over half of the cases of
      blindness in Pakistan. One in eight blind adults has visual loss from sequelae of
      cataract surgery. Services for refractive errors need to be further expanded and
      integrated into eye care services, particularly those serving rural populations.

PMID- 17229807
TI  - Cystoid puncture for chronic cystoid macular oedema.
AB  - OBJECTIVE: To evaluate the new surgical technique of cystoid macular oedema
      puncture (CMOP) in patients with longstanding cystoid macular oedema refractory
      to standard treatments. DESIGN: Interventional, retrospective case series
      METHODS: Retrospective review of patients with chronic cystoid macular oedema
      from vascular retinopathy for whom maximal medical or surgical treatment failed
      and who underwent pars plana vitrectomy and CMOP. Clinical findings, best
      corrected Snellen visual acuity, stereo colour fundus photography, intravenous
      fluorescein angiograms, and optical coherence tomography were obtained before and
      after treatment to evaluate the efficacy and safety of the treatment. RESULTS:
      Seven patients were included in the study. Cystoid macular oedema was due to
      diabetic retinopathy in five patients, central retinal vein occlusion in one
      patient and branch retinal vein occlusion in one patient. Preoperative
      intravitreal steroids failed for all patients, and three patients also had focal
      grid photocoagulation. Previous pars plana vitrectomy, with elevation of the
      posterior hyaloid, internal limiting membrane peeling, and intravitreal steroid
      injection, had failed in three patients. The median time to CMOP was 488 days.
      Resolution or improvement of cystoid oedema occurred in all patients as
      determined by fluorescein angiography or optical coherence tomography, or both.
      However, visual acuity was unchanged in five patients, declined in one patient
      and stable in one patient. CONCLUSIONS: Although cystoid macular oedema does
      improve quantitatively after CMOP, the technique fails to improve visual acuity
      in patients.

PMID- 17229808
TI  - Inhibition of PI3-kinase signaling by glucocorticoids results in increased
      branched-chain amino acid degradation in renal epithelial cells.
AB  - Phosphatidylinositol 3-kinase(PI3K) is a pivotal enzyme involved in the control
      of a variety of diverse metabolic functions. Glucocorticoids have been shown to
      attenuate PI3K signaling in some nonrenal cell types, raising the possibility
      that some physiological effects of glucocorticoids in renal cells may be achieved
      by a similar mechanism. Therefore, we tested whether glucocorticoids affect
      signaling through the insulin receptor substrate (IRS)-1/PI3K/Akt signaling
      cascade in LLC-PK1-GR101 renal epithelial cells. Treatment of cells with
      dexamethasone for 24 h: 1) suppressed IRS-1-associated PI3K activity and Akt
      phosphorylation, 2) increased the level of the PI3K p85 regulatory subunit but
      not the p110 catalytic subunit, and 3) induced the phosphorylation of IRS-1 on
      inhibitory Ser(307). We have previously reported that glucocorticoids increase
      branched-chain ketoacid dehydrogenase (BCKD) activity in LLC-PK1-GR101 cells.
      This response was achieved, in part, by alterations in the transcription of BCKD
      subunits and BCKD kinase, which inactivates the enzyme complex by
      phosphorylation. Therefore, we tested whether inhibition of PI3K signaling would
      mimick glucocorticoids by increasing branched-chain amino acid degradation.
      Expression of a dominant negative PI3K p85 regulatory subunit (Adp85DeltaiSH2)
      increased BCKD activity, and dexamethasone did not further stimulate enzyme
      activity. Inhibition of PI3K using LY-294002 increased the transcription of the
      BCKD E2 subunit but not the E1alpha subunit or BCKD kinase. Thus, glucocorticoids
      inhibit signaling through the IRS-1/PI3K/Akt pathway with a consequence of
      increased branched-chain amino acid catabolism.

PMID- 17229809
TI  - Recruitment of NADH shuttling in pressure-overloaded and hypertrophic rat hearts.
AB  - Glucose metabolism in the heart requires oxidation of cytosolic NADH from
      glycolysis. This study examines shuttling reducing equivalents from the cytosol
      to the mitochondria via the activity and expression of the oxoglutarate-malate
      carrier (OMC) in rat hearts subjected to 2 wk (Hyp2, n = 6) and 10 wk (Hyp10, n =
      8) of pressure overload hypertrophy vs. that of sham-operated rats (Sham2, n = 6;
      and Sham10, n = 7). Moderate aortic banding produced increased atrial natriuretic
      factor (ANF) mRNA expression at 2 and 10 wk, but only at 10 wk did hearts develop
      compensatory hypertrophy (33% increase, P < 0.05). Isolated hearts were perfused
      with the short-chain fatty acid [2,4-(13)C(2)]butyrate (2 mM) and glucose (5 mM)
      to enable dynamic-mode (13)C NMR of intermediate exchange across OMC. OMC flux
      increased before the development of hypertrophy: Hyp2 = 9.6 +/- 2.1 vs. Sham2 =
      3.7 +/- 1.2 muM.min(-1).g dry wt(-1), providing an increased contribution of
      cytosolic NADH to energy synthesis in the mitochondria. With compensatory
      hypertrophy, OMC flux returned to normal: Hyp10 = 3.9 +/- 1.7 vs. Sham10 = 3.8 +/
      1.2 muM.g(-1).min(-1). Despite changes in activity, no differences in OMC
      expression occurred between Hyp and Sham groups. Elevated OMC flux represented
      augmented cytosolic NADH shuttling, coupled to increased nonoxidative glycolysis,
      in response to hypertrophic stimulus. However, development of compensatory
      hypertrophy moderated the pressure-induced elevation in OMC flux, which returned
      to control levels. The findings indicate that the challenge of pressure overload
      increases cytosolic redox state and its contribution to mitochondrial oxidation
      but that hypertrophy, before decompensation, alleviates this stress response.

PMID- 17229810
TI  - Functional analysis of the aquaporin gene family in Caenorhabditis elegans.
AB  - Aquaporin channels facilitate the transport of water, glycerol, and other small
      solutes across cell membranes. The physiological roles of many aquaporins remain
      unclear. To better understand aquaporin function, we characterized the aquaporin
      gene family in the nematode Caenorhabditis elegans. Eight canonical aquaporin
      encoding genes (aqp) are present in the worm genome. Expression of aqp-2, aqp-3,
      aqp-4, aqp-6, or aqp-7 in Xenopus oocytes increased water permeability five- to
      sevenfold. Glycerol permeability was increased three to sevenfold by expression
      of aqp-1, aqp-3, or aqp-7. Green fluorescent protein transcriptional and
      translational reporters demonstrated that aqp genes are expressed in numerous C.
      elegans cell types, including the intestine, excretory cell, and hypodermis,
      which play important roles in whole animal osmoregulation. To define the role of
      C. elegans aquaporins in osmotic homeostasis, we isolated deletion alleles for
      four aqp genes, aqp-2, aqp-3, aqp-4, and aqp-8, which are expressed in
      osmoregulatory tissues and mediate water transport. Single, double, triple, and
      quadruple aqp mutant animals exhibited normal survival, development, growth,
      fertility, and movement under normal and hypertonic culture conditions. aqp-2;aqp
      3;aqp-4;aqp-8 quadruple mutants exhibited a slight defect in recovery from
      hypotonic stress but survived hypotonic stress as well as wild-type animals.
      These results suggest that C. elegans aquaporins are not essential for whole
      animal osmoregulation and/or that deletion of aquaporin genes activates
      mechanisms that compensate for loss of water channel function.

PMID- 17229811
TI  - Developmental regulation of the mouse IGF-I exon 1 promoter region by calcineurin
      activation of NFAT in skeletal muscle.
AB  - Skeletal muscle development and growth are regulated through multiple signaling
      pathways that include insulin-like growth factor I (IGF-I) and calcineurin
      activation of nuclear factor of activated T cell (NFAT) transcription factors.
      The developmental regulation and molecular mechanisms that control IGF-I gene
      expression in murine embryos and in differentiating C2C12 skeletal myocytes were
      examined. IGF-I is expressed in developing skeletal muscle, and its embryonic
      expression is significantly reduced in embryos lacking both NFATc3 and NFATc4.
      During development, the IGF-I exon 1 promoter is active in multiple organ
      systems, including skeletal muscle, whereas the alternative exon 2 promoter is
      expressed predominantly in the liver. The IGF-I exon 1 promoter flanking sequence
      includes two highly conserved regions that contain NFAT consensus binding
      sequences. One of these conserved regions contains a calcineurin/NFAT-responsive
      regulatory region that is preferentially activated by NFATc3 in C2C12 skeletal
      muscle cells and NIH3T3 fibroblasts. This NFAT-responsive region contains three
      clustered NFAT consensus binding sequences, and mutagenesis experiments
      demonstrated the requirement for two of these in calcineurin or NFATc3
      responsiveness. Chromatin immunoprecipitation analyses demonstrated that
      endogenous IGF-I genomic sequences containing these conserved NFAT binding
      sequences interact preferentially with NFATc3 in C2C12 cells. Together, these
      experiments demonstrated that a NFAT-rich regulatory element in the IGF-I exon 1
      promoter flanking region is responsive to calcineurin signaling and NFAT
      activation in skeletal muscle cells. The identification of a calcineurin/NFAT
      responsive element in the IGF-I gene represents a potential mechanism of
      intersection of these signaling pathways in the control of muscle development and
      homeostasis.

PMID- 17229812
TI  - Shrinkage insensitivity of NKCC1 in myosin II-depleted cytoplasts from Ehrlich
      ascites tumor cells.
AB  - Protein phosphorylation/dephosphorylation and cytoskeletal reorganization
      regulate the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) during osmotic shrinkage;
      however, the mechanisms involved are unclear. We show that in cytoplasts, plasma
      membrane vesicles detached from Ehrlich ascites tumor cells (EATC) by
      cytochalasin treatment, NKCC1 activity evaluated as bumetanide-sensitive (86)Rb
      influx was increased compared with the basal level in intact cells yet could not
      be further increased by osmotic shrinkage. Accordingly, cytoplasts exhibited no
      regulatory volume increase after shrinkage. In cytoplasts, cortical F-actin
      organization was disrupted, and myosin II, which in shrunken EATC translocates to
      the cortical region, was absent. Moreover, NKCC1 activity was essentially
      insensitive to the myosin light chain kinase (MLCK) inhibitor ML-7, a potent
      blocker of shrinkage-induced NKCC1 activity in intact EATC. Cytoplast NKCC1
      activity was potentiated by the Ser/Thr protein phosphatase inhibitor calyculin
      A, partially inhibited by the protein kinase A inhibitor H89, and blocked by the
      broad protein kinase inhibitor staurosporine. Cytoplasts exhibited increased
      protein levels of NKCC1, Ste20-related proline- and alanine-rich kinase (SPAK),
      and oxidative stress response kinase 1, yet they lacked the shrinkage-induced
      plasma membrane translocation of SPAK observed in intact cells. The basal
      phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was increased
      in cytoplasts compared with intact cells, yet in contrast to the substantial
      activation in shrunken intact cells, p38 MAPK could not be further activated by
      shrinkage of the cytoplasts. Together these findings indicate that shrinkage
      activation of NKCC1 in EATC is dependent on the cortical F-actin network, myosin
      II, and MLCK.

PMID- 17229813
TI  - Cardiac fibroblasts influence cardiomyocyte phenotype in vitro.
AB  - Cardiac fibroblasts impact myocardial development and remodeling through
      intercellular contact with cardiomyocytes, but less is known about noncontact,
      profibrotic signals whereby fibroblasts alter cardiomyocyte behavior. Fibroblasts
      and cardiomyocytes were harvested from newborn rat ventricles and separated by
      serial digestion and gradient centrifugation. Cardiomyocytes were cultured in 1)
      standard medium, 2) standard medium diluted 1:1 with PBS, or 3) standard medium
      diluted 1:1 with medium conditioned > or =72 h by cardiac fibroblasts. Serum
      concentrations were held constant under all media conditions, and complete medium
      exchanges were performed daily. Cardiomyocytes began contracting within 24 h at
      clonal or mass densities with <5% of cells expressing vimentin.
      Immunocytochemical analysis revealed progressive expression of alpha-smooth
      muscle actin in cardiomyocytes after 24 h in all conditions. Only cardiomyocytes
      in fibroblast-conditioned medium stopped contracting by 72 h. There was a
      significant, sustained increase in vimentin expression specific to these cultures
      (means +/- SD: conditioned 46.3 +/- 6.0 vs. control 5.3 +/- 2.9%, P < 0.00025)
      typically with cardiac myosin heavy chain coexpression. Proteomics assays
      revealed 10 cytokines (VEGF, GRO/KC, monocyte chemoattractant protein-1, leptin,
      macrophage inflammatory protein-1alpha, IL-6, IL-10, IL-12p70, IL-17, and tumor
      necrosis factor-alpha) at or below detection levels in unconditioned medium that
      were significantly elevated in fibroblast-conditioned medium. Latent transforming
      growth factor-beta and RANTES were present in unconditioned medium but rose to
      higher levels in conditioned medium. Only granulocyte-macrophage colony
      stimulating factor was present above threshold levels in standard medium but
      decreased with fibroblast conditioning. These data indicated that under the
      influence of fibroblast-conditioned medium, cardiomyocytes exhibited marked
      hypertrophy, diminished contractile capacity, and phenotype plasticity distinct
      from the dedifferentiation program present under standard culture conditions.

PMID- 17229814
TI  - Obligatory role for phospholipase C-gamma(1) in villin-induced epithelial cell
      migration.
AB  - While there is circumstantial evidence to suggest a requirement for phospholipase
      C-gamma(1) (PLC-gamma(1)) in actin reorganization and cell migration, few studies
      have examined the direct mechanisms that link regulators of the actin
      cytoskeleton with this crucial signaling molecule. This study was aimed to
      examine the role that villin, an epithelial cell-specific actin-binding protein,
      and its ligand PLC-gamma(1) play in migration in intestinal and renal epithelial
      cell lines that endogenously or ectopically express human villin. Basal as well
      as epidermal growth factor (EGF)-stimulated cell migration was accompanied by
      tyrosine phosphorylation of villin and its association with PLC-gamma(1).
      Inhibition of villin phosphorylation prevented villin-PLC-gamma(1) complex
      formation as well as villin-induced cell migration. The absolute requirement for
      PLC-gamma(1) in villin-induced cell migration was demonstrated by measuring cell
      motility in PLC-gamma(1)(-/-) cells and by downregulation of endogenous PLC
      gamma(1). EGF-stimulated direct interaction of villin with the Src homology
      domain 2 domain of PLC-gamma(1) at the plasma membrane was demonstrated in living
      cells by using fluorescence resonance energy transfer. These results demonstrate
      that villin provides an important link between the activation of phosphoinositide
      signal transduction pathway and epithelial cell migration.

PMID- 17229815
TI  - Glycosylation of serum ribonuclease 1 indicates a major endothelial origin and
      reveals an increase in core fucosylation in pancreatic cancer.
AB  - Human pancreatic ribonuclease 1 (RNase 1) is a glycoprotein expressed mainly by
      the pancreas and also found in endothelial cells. The diagnosis of pancreatic
      cancer (PaC) remains difficult and therefore the search for sensitive and
      specific markers is required. Previous studies showed that RNase 1 from human
      healthy pancreas contained only neutral glycans, whereas RNase 1 from PaC cell
      lines contained sialylated structures. To determine whether these glycan tumor
      cell-associated changes were also characteristic of serum RNase 1 and could be
      used as a marker of PaC, we have analyzed the glycosylation of serum RNase 1. The
      origin of serum RNase 1 was also investigated. Serum RNase 1 from two PaC
      patients and two controls was purified and the glycans analyzed by high
      performance liquid chromatography (HPLC)-based sequencing and mass spectrometry.
      Although normal and tumor serum RNase 1 contained the same glycan structures,
      there was an increase of 40% in core fucosylation in the main sialylated
      biantennary glycans in the PaC serum RNase 1. This change in proportion would be
      indicative of a subset of tumor-associated glycoforms of RNase 1, which may
      provide a biomarker for PaC. Two-dimensional electrophoresis of the RNase 1 from
      several endothelial cell lines, EA.hy926, human umbilical vein endothelial cells
      (HUVEC), human mammary microvessel endothelial cells (HuMMEC), and human lung
      microvessel endothelial cells (HuLEC), showed basically the same pattern and was
      also very similar to that of serum RNase 1. RNase 1 from EA.hy926 was then
      purified and presented a glycosylation profile very similar to that from serum
      RNase 1, suggesting that endothelial cells are the main source of this enzyme.

PMID- 17229816
TI  - Substitution of osteoporotic alveolar bone by biphasic calcium phosphate/poly-DL
      lactide-co-glycolide biomaterials.
AB  - Lost bone tissue due to osteoporosis makes dentistry very difficult. The aim of
      thisstudy is to reconstruct the bone tissue with composite biomaterials and to
      estimate the optical density and alveolar ridge height of the mandible. Research
      is conducted on 30 postmenopausal women aged from 46 to 62 years, with diagnosed
      osteoporosis and defects in alveolar bones caused by extraction of
      paradontopathic teeth, enucleation of cysts and periapical changes, extraction of
      impacted teeth,or by trauma.Biphasic calcium phosphate/poly-DL-lactide-co
      glycolide (BCP/PLGA) composite is implanted into the defects of alveolar bones.
      Six weeks after implantation of BCP/PLGA, the alveolar bone density in the region
      of premolars on the experimental side of the jaw is found to be lower than that
      on the untreated, control, side of the jaw. On thecontrary, 24 weeks after
      implantation, it is significantly higher compared with the density of the control
      side. A significant increase in optical density of alveolar bones in the region
      of premolars on the experimental side compared with the control one is noticed.
      These results indicate a high level of osteoregeneration and osteoblast activity.
      Synthetic BCP/PLGA composite belongs to the group of biomaterials, which
      facilitate formation of new bones and rehabilitation of alveolar bones weakened
      by osteoporosis. Because of its osteoconductive characteristics, BCP/PLGA
      composite is supposed to be the material of choice for replacement of bone tissue
      in the future.

PMID- 17229817
TI  - Impaired V(D)J recombination and increased apoptosis among B cell precursors in
      the bone marrow of c-Abl-deficient mice.
AB  - Previous studies on c-Abl-deficient mice have shown high post-natal mortality and
      lymphopenia. However, the mechanisms by which c-Abl may influence B lymphopoiesis
      remain obscure. In this study, we analyzed B cell sub-populations at various
      differentiation stages in the bone marrow (BM) of c-Abl-deficient mice.
      Phenotypic analyses revealed that c-Abl(-/-) pro-B cells were reduced to half of
      normal incidence and absolute number, while pre-B cells showed an even greater
      reduction. Both c-Abl(-/-) pro-B and pre-B cell populations showed considerably
      elevated apoptosis ex vivo and in short-term culture but their cell cycle
      progression was not impaired. In contrast, apoptosis of immature IgM(+)IgD(-) B
      lymphocytes remained at normal control levels. Inhibition of c-Abl activity by
      STI571 in normal BM cultures significantly increased apoptosis in B cell
      precursors while the survival of immature B cells was not affected. To determine
      whether c-Abl deficiency affects Ig heavy-chain rearrangement, we found that the
      frequency of V(D)J recombination was markedly reduced by 15-fold in c-Abl(-/-)
      pro-B cells compared with the control values. However, no perturbation in the
      levels of signal-end recombination intermediates was found. Taken together, we
      propose that c-Abl mediates a stage-specific anti-apoptotic response in precursor
      B cells and is required for efficient V(D)J recombination during B cell
      development.

PMID- 17229818
TI  - AsialoGM1+CD8+ central memory-type T cells in unimmunized mice as novel
      immunomodulator of IFN-gamma-dependent type 1 immunity.
AB  - In unimmunized specific pathogen-free mice, there are unique memory-type CD8(+) T
      cell populations expressing asialoGM1 (ASGM1). These cells were classified into
      central memory-type T cells (T(CMT)) judging from their expression profile of
      CD44, IL-2Rbeta, CD62L and CCR7 cell-surface molecules. Among CD44(high)CD8(+) so
      called memory CD8(+) T cell population, ASGM1(+)CD44(high)CD8(+) T(CMT), but not
      ASGM1(-)CD44(high)CD8(+) memory T cells, produced IFN-gamma by stimulation with
      anti-CD3 mAb. The physiological significance of ASGM1(+)CD8(+) T(CMT) as early
      source of IFN-gamma was also demonstrated in vivo. Namely, intravenous injection
      of anti-CD3 mAb (2 microg) resulted in early activation of IFN-gamma-producing
      ASGM1(+)CD8(+) T(CMT) cells as well as NKT and NK cells. Unexpectedly, however,
      few IFN-gamma-producing CD4(+) T cells were detected until 4 h after anti-CD3 mAb
      administration. Thus, ASGM1(+)CD8(+) T(CMT) were demonstrated to be early IFN
      gamma producer, which may be crucial for T(h)1-dependent cellular immunity.
      Indeed, co-culture of naive CD4(+) T cells with ASGM1(+)CD8(+) T(CMT) but not
      ASGM1(-)CD8(+) T cells caused a great acceleration of IFN-gamma-producing T(h)1
      cells in vitro. Finally, we found that T(h)1-prone C57BL/6 mice possessed higher
      percentage (10%) of ASGM1(+)CD8(+) T(CMT) in CD8(+) T cells compared with that
      (3%) of T(h)2-prone BALB/c mice. Moreover, ASGM1(+)CD8(+) T(CMT) derived from
      C57BL/6 mice produced higher levels of IFN-gamma compared with those from BALB/c
      mice. Thus, ASGM1(+)CD8(+) T(CMT), whose differentiation in vivo is genetically
      controlled, appear to play a critical role in the control of type 1 immunity,
      which is essential for therapy of tumors and infectious diseases.

PMID- 17229819
TI  - Adaptive response to DNA and chromosomal damage induced by X-rays in human blood
      lymphocytes.
AB  - Nucleoid sedimentation, single-cell gel electrophoresis (comet assay) and
      premature chromosome condensation (PCC) technique were utilized to estimate the
      involvement of DNA strand breaks and chromosomal damage in radio-adaptive
      response of stimulated human lymphocytes. Conditioning of cells with 0.02 Gy X
      rays rendered them more resistant to single- and double-strand DNA breaks
      produced by 1 Gy challenging treatment as revealed by the sedimentation behaviour
      of the nucleoids and the comet assay. Nucleoid sedimentation also demonstrated
      that adaptive reaction towards X-ray-induced DNA damage is favoured in the
      presence of oxygen. A concomitant decrease in the amount of interphase
      chromosomal breaks visualized by PCC under the same experimental conditions was
      observed. Data indicate that adaptation of human lymphocytes to X-rays is tightly
      linked to the reduced susceptibility towards generation of DNA and chromosomal
      breaks. It is proposed that the very persistence of DNA strand discontinuities
      might serve as a triggering signal for the adaptation of human lymphocytes
      against ionizing radiation exposure.

PMID- 17229820
TI  - Granular cells of the mormyrid electrosensory lobe and postsynaptic control over
      presynaptic spike occurrence and amplitude through an electrical synapse.
AB  - Primary afferent fibers from the electroreceptors of mormyrid electric fish use a
      latency code to signal the intensity of electrical current evoked by the fish's
      own electric organ discharge (EOD). The afferent fibers terminate centrally in
      the deep and superficial granular layers of the electrosensory lobe with
      morphologically mixed chemical-electrical synapses. The granular cells in these
      layers seem to decode afferent latency through an interaction between primary
      afferent input and a corollary discharge input associated with the EOD motor
      command. We studied the physiology of deep and superficial granular cells in a
      slice preparation with whole cell patch recording and electrical stimulation of
      afferent fibers. Afferent stimulation evoked large all-or-none electrical
      excitatory postsynaptic potentials (EPSPs) and large all or none GABAergic
      inhibitory postsynaptic potentials (IPSPs) in both superficial and deep granular
      cells. The amplitudes of the electrical EPSPs depended on postsynaptic membrane
      potential, with maximum amplitudes at membrane potentials between -65 and -110
      mV. Hyperpolarization beyond this level resulted in either the abrupt
      disappearance of EPSPs, a step-like reduction to a smaller EPSP, or a graded
      reduction in EPSP amplitude. Depolarization to membrane potentials lower than
      that yielding a maximum caused a linear decrease in EPSP amplitude, with EPSP
      amplitude reaching 0 mV at potentials between -55 and -40 mV. We suggest that the
      dependence of EPSP size on postsynaptic membrane potential is caused by close
      linkage of pre- and postsynaptic membrane potentials through a high-conductance
      gap junction. We also suggest that this dependence may result in functionally
      important nonlinear interactions between synaptic inputs.

PMID- 17229821
TI  - Role of membrane potential in calcium signaling during rhythmic bursting in
      tritonia swim interneurons.
AB  - Rhythmic bursting in neurons is accompanied by dynamic changes in intracellular
      Ca(2+) concentration. These Ca(2+) signals may be caused by membrane potential
      changes during bursting and/or by synaptic inputs. We determined that membrane
      potential is responsible for most, if not all, of the cytoplasmic Ca(2+) signal
      recorded during rhythmic bursting in two neurons of the escape swim central
      pattern generator (CPG) of the mollusk, Tritonia diomedea: ventral swim
      interneuron B (VSI) and cerebral neuron 2 (C2). Ca(2+) signals were imaged with a
      confocal laser scanning microscope while the membrane potential was recorded at
      the soma. During the swim motor pattern (SMP), Ca(2+) signals in both neurons
      transiently increased during each burst of action potentials with a more rapid
      decay in secondary than in primary neurites. VSI and C2 were then voltage-clamped
      at the soma, and each neuron's own membrane potential waveform recorded during
      the SMP was played back as the voltage command. In all regions of VSI, this
      completely reproduced the amplitude and time course of Ca(2+) signals observed
      during the SMP, but in C2, the amplitude was lower in the playback experiments
      than during the SMP, possibly due to space clamp problems. Therefore in VSI, the
      cytoplasmic Ca(2+) signal during the SMP can be accounted for by its membrane
      potential excursions, whereas in C2 the membrane potential excursions can account
      for most of the SMP Ca(2+) signal.

PMID- 17229822
TI  - Involvement of persistent Na+ current in spike initiation in primary sensory
      neurons of the rat mesencephalic trigeminal nucleus.
AB  - It was recently shown that the persistent Na(+) current (I(NaP)) is generated in
      the proximal axon in response to somatic depolarization in neocortical pyramidal
      neurons, although the involvement of I(NaP) in spike initiation is still unclear.
      Here we show a potential role of I(NaP) in spike initiation of primary sensory
      neurons in the mesencephalic trigeminal nucleus (MTN) that display a
      backpropagation of the spike initiated in the stem axon toward the soma in
      response to soma depolarization. Riluzole (10 muM) and tetrodotoxin (TTX, 10 nM)
      caused an activation delay or a stepwise increase in the threshold for evoking
      soma spikes (S-spikes) without affecting the spike itself. Simultaneous patch
      clamp recordings from the soma and axon hillock (AH) revealed that bath
      application of 50 nM TTX increased the delay in spike activation in response to
      soma depolarization, leaving the spike-backpropagation time from the AH to soma
      unchanged. This indicates that the increase in activation delay occurred in the
      stem axon. Furthermore, under a decreasing intracellular concentration gradient
      of QX-314 from the soma to AH created by QX-314-containing and QX-314-free patch
      pipettes, the amplitude and maximum rate of rise (MRR) of AH-spikes decreased
      with an increase in the activation delay following repetition of current-pulse
      injections, whereas S-spikes displayed decreases of considerably lesser degree in
      amplitude and MRR. This suggests that compared to S-spikes, AH-spikes more
      accurately reflect the attenuation of axonal spike by QX-314, consistent with the
      nature of spike backpropagation. These observations strongly suggest that low
      voltage-activated I(NaP) is involved in spike initiation in the stem axon of MTN
      neurons.

PMID- 17229823
TI  - Physiologically based controller for generating overground locomotion using
      functional electrical stimulation.
AB  - The physiological control of stepping is governed both by signals descending from
      supraspinal systems and by circuitry residing within the lumbosacral spinal cord.
      The goal of this study was to evaluate the capacity of physiologically based
      controllers to restore functional overground locomotion after neurological
      damage, such as spinal cord injury when used in conjunction with functional
      electrical stimulation. For this purpose we implemented and tested two
      controllers: 1) an intrinsically timed system that generated a predetermined
      rhythmic output and 2) a sensory-based system that used feedback signals to make
      appropriate transitions between the unloaded (flexion) and loaded (extension)
      phases of the gait cycle. A third controller, a combination of the intrinsically
      timed and sensory-driven controllers, was implemented and two sessions were
      conducted to demonstrate the functional advantages of this approach. The
      controllers were tested in anesthetized cats, implanted with intramuscular
      electrodes in six major extensor and flexor muscles of the hindlimbs. The cats
      were partially supported on a sliding trolley that was propelled by the hindlimbs
      along a 2.5-m instrumented walkway. Ground reaction forces and limb positions
      were measured by force plates in the walkway and by accelerometers secured to the
      legs of the cat, respectively. The controllers were used to generate patterns of
      stimulation that would elicit alternating flexor (swing) and extensor (stance)
      movements in the hindlimbs. Using either the intrinsically timed or sensory
      driven controllers, the cats were able to travel a distance of 2.5 m, taking five
      to 12 steps. Functional stepping sequences were more easily achieved using the
      intrinsically timed controller as the result of a lower sensitivity to the
      selection of initial stimulation parameters. However, unlike the sensory-driven
      controller, the intrinsically timed controller was unable to adjust to overcome
      walkway resistance and muscle fatigue. Neither system was consistently able to
      ensure load-bearing stepping. Therefore we propose the use of a "combined
      controller" that relies heavily on intrinsic timing but that can be reset based
      on sensory signals. A combined controller such as this one may provide the best
      solution for restoring robust overground locomotion after spinal cord injury.

PMID- 17229824
TI  - Afferent responses during experimentally induced semicircular canalithiasis.
AB  - Benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder that
      results in brief periods of vertigo and nystagmus, when the head is tipped
      relative to gravity. Symptoms are commonly attributed to the pathological
      presence of heavy calcium carbonate particles within the lumen of the
      semicircular canal(s)-a condition termed canalithiasis. In the present work, we
      induced canalithiasis in an animal model (oyster toadfish, Opsanus tau) by
      introducing heavy glass microbeads into the lumen of the lateral semicircular
      canal. Bead movement under the action of gravity and canal afferent nerve
      discharge were recorded in vivo. When the head was oriented nose-down, beads
      moved toward the nose and the lateral canal afferent discharge rate increased.
      Afferents that normally encoded angular velocity during oscillatory head
      rotations responded with tonic increases in the discharge rate during gravity
      dependent bead movement. Other afferents, such as the units that rapidly adapt to
      a step increase in angular head velocity, responded with an initial increase in
      discharge rate followed by a period of adaptation. Afferent responses occurred in
      the complete absence of head movement and quantify the pathological inputs to the
      brain that arise from canalithiasis. The magnitude and time course of the
      responses reported here are sufficient to explain the symptoms of BPPV.

PMID- 17229825
TI  - Effects of compounds that influence IK (KCNN4) channels on afterhyperpolarizing
      potentials, and determination of IK channel sequence, in guinea pig enteric
      neurons.
AB  - The late afterhyperpolarizing potential (AHP) that follows the action potential
      in intrinsic primary afferent neurons of the gastrointestinal tract has a
      profound influence on their firing patterns. There has been uncertainty about the
      identity of the channels that carry the late AHP current, especially in guinea
      pigs, where the majority of the physiological studies have been made. In the
      present work, the late AHP was recorded with intracellular microelectrodes from
      myenteric neurons in the guinea pig small intestine. mRNA was extracted from the
      ganglia to determine the identity of the guinea pig intermediate conductance
      potassium (I(K)) channel gene transcript. The late AHP was inhibited by two
      blockers of I(K) channels, TRAM34 (0.1-1 microM) and clotrimazole (10 microM),
      and was enhanced by the potentiator of the opening of these channels, DC-EBIO
      (100 nM). Action potential characteristics were unchanged by TRAM34 or DC-EBIO.
      The full sequence of the gene transcript and the deduced amino acid sequence were
      determined from extracts including myenteric ganglia and from bladder urothelium,
      which is a rich source of I(K) channel mRNA. This showed that the guinea pig
      sequence has a high degree of homology with other mammalian sequences but that
      the guinea pig channel lacks a phosphorylation site that was thought to be
      critical for channel regulation. It is concluded that the channels that carry the
      current of the late afterhyperpolarizing potential in guinea pig enteric neurons
      are I(K) channels.

PMID- 17229826
TI  - Reelin signaling facilitates maturation of CA1 glutamatergic synapses.
AB  - Reelin signaling through the low-density lipoprotein receptor family members,
      apoliproprotein E receptor 2 (apoER2) and very-low-density lipoprotein receptor
      (VLDLR), plays a pivotal role in dictating neuronal lamination during embryonic
      brain development. Recent evidence suggests that this signaling system also plays
      a role in the postnatal brain to modulate synaptic transmission, plasticity, and
      cognitive behavior, mostly likely due to a functional coupling with N-methyl-d
      aspartate (NMDA) receptors. In this study, we investigated the effects of reelin
      on the maturation of CA1 glutamatergic function using electrophysiological and
      biochemical approaches. In cultured hippocampal slices, reelin treatment
      increased the amplitude of AMPAR-mediated miniature excitatory postsynaptic
      currents and the evoked AMPA/NMDA receptor current ratios. In addition, reelin
      treatment also reduced the number of silent synapses, facilitated a developmental
      switch from NR2B to NR2A of NMDARs, and increased surface expression of AMPARs in
      CA1 tissue. In cultured hippocampal neurons from reeler embryos, reduced numbers
      of AMPAR subunit GluR1 and NMDAR subunit NR1 clustering were observed compared
      with those obtained from wild-type embryos. Supplementing reelin in the reeler
      culture obliterated these genotypic differences. These results demonstrate that
      reelin- and lipoprotein receptor-mediated signaling may operate during
      developmental maturation of hippocampal glutamatergic function and thus represent
      a potential important mechanism for controlling synaptic strength and plasticity
      in the postnatal hippocampus.

PMID- 17229827
TI  - Eye, head, and body coordination during large gaze shifts in rhesus monkeys:
      movement kinematics and the influence of posture.
AB  - Coordinated movements of the eye, head, and body are used to redirect the axis of
      gaze between objects of interest. However, previous studies of eye-head gaze
      shifts in head-unrestrained primates generally assumed the contribution of body
      movement to be negligible. Here we characterized eye-head-body coordination
      during horizontal gaze shifts made by trained rhesus monkeys to visual targets
      while they sat upright in a standard primate chair and assumed a more natural
      sitting posture in a custom-designed chair. In both postures, gaze shifts were
      characterized by the sequential onset of eye, head, and body movements, which
      could be described by predictable relationships. Body motion made a small but
      significant contribution to gaze shifts that were > or =40 degrees in amplitude.
      Furthermore, as gaze shift amplitude increased (40-120 degrees ), body
      contribution and velocity increased systematically. In contrast, peak eye and
      head velocities plateaued at velocities of approximately 250-300 degrees /s, and
      the rotation of the eye-in-orbit and head-on-body remained well within the
      physical limits of ocular and neck motility during large gaze shifts, saturating
      at approximately 35 and 60 degrees , respectively. Gaze shifts initiated with the
      eye more contralateral in the orbit were accompanied by smaller body as well as
      head movement amplitudes and velocities were greater when monkeys were seated in
      the more natural body posture. Taken together, our findings show that body
      movement makes a predictable contribution to gaze shifts that is systematically
      influenced by factors such as orbital position and posture. We conclude that body
      movements are part of a coordinated series of motor events that are used to
      voluntarily reorient gaze and that these movements can be significant even in a
      typical laboratory setting. Our results emphasize the need for caution in the
      interpretation of data from neurophysiological studies of the control of saccadic
      eye movements and/or eye-head gaze shifts because single neurons can code motor
      commands to move the body as well as the head and eyes.

PMID- 17229828
TI  - What does the brain do when you fake it? An FMRI study of pantomimed and real
      grasping.
AB  - Given that studying neural bases of actions is very challenging with fMRI,
      numerous experiments have used pantomimed actions as a proxy to studying neural
      circuits of real actions. However, the underlying assumption that the same neural
      mechanisms mediate real and pantomimed actions has never been directly tested.
      Moreover, the assumption is called into question by neuropsychological evidence
      suggesting that real actions depend on the dorsal stream of visual processing
      whereas pretend actions also recruit the ventral stream. Here, we directly tested
      these ideas in neurologically intact subjects. Ten right-handed participants
      performed four tasks: 1) grasping real three-dimensional objects, 2) reaching
      toward the objects and touching them with the knuckle without hand preshaping, 3)
      pantomimed grasping in an adjacent location where no object was present, and 4)
      pantomimed reaching toward an adjacent location. As expected, in the anterior
      intraparietal area, there was significantly higher activation during real
      grasping than that during real reaching. However, the activation difference
      between pantomimed grasping and pantomimed reaching did not reach statistical
      significance. There was also no effect of pantomimed grasping within the ventral
      stream, including an object-selective area in the lateral occipital cortex.
      Instead, we found that pantomimed grasping was mediated by right-hemisphere
      activation, particularly the right parietal cortex. These results suggest that
      areas typically invoked by real actions may not necessarily be driven by "fake"
      actions. Moreover, pantomimed grasping may not tap object-related areas within
      the ventral stream, but rather may rely on mechanisms within the right hemisphere
      that are recruited by artificial and less practiced actions.

PMID- 17229829
TI  - Three-dimensional eye-head coordination after injection of muscimol into the
      interstitial nucleus of Cajal (INC).
AB  - The interstitial nucleus of Cajal (INC) is thought to be the "neural integrator"
      for torsional/vertical eye position and head posture. Here, we investigated the
      coordination of eye and head movements after reversible INC inactivation. Three
      dimensional (3-D) eye-head movements were recorded in three head-unrestrained
      monkeys using search coils. INC sites were identified by unit
      recording/electrical stimulation and then reversibly inactivated by 0.3 mul of
      0.05% muscimol injection into 26 INC sites. After muscimol injection, the eye and
      head 1) began to drift (an inability to maintain stable fixation) torsionally:
      clockwise (CW)/counterclockwise (CCW) after left/right INC inactivation
      respectively. 2) The eye and head tilted torsionally CW/CCW after left/right INC
      inactivation, respectively. Horizontal gaze/head drifts were inconsistently
      present and did not result in considerable position offsets. Vertical eye drift
      was dependent on both vertical eye position and the magnitude of the previous
      vertical saccade, as in head-fixed condition. This correlation was smaller for
      gaze and head drift, suggesting that the gaze and head deficits could not be
      explained by a first-order integrator model. Ocular counterroll (OC) was
      completely disrupted. The gain of torsional vestibuloocular reflex (VOR) during
      spontaneous eye and head movements was reduced by 22% in both CW/CCW directions
      after either left or right INC inactivation. Our results suggest a complex
      interdependence of eye and head deficits after INC inactivation during fixation,
      gaze shifts, and VOR. Some of our results resemble the symptoms of spasmodic
      torticollis (ST).

PMID- 17229830
TI  - Dopamine D1/5 receptor-mediated long-term potentiation of intrinsic excitability
      in rat prefrontal cortical neurons: Ca2+-dependent intracellular signaling.
AB  - Prefrontal cortex (PFC) dopamine D1/5 receptors modulate long- and short-term
      neuronal plasticity that may contribute to cognitive functions. Synergistic to
      synaptic strength modulation, direct postsynaptic D1/5 receptor activation also
      modulates voltage-dependent ionic currents that regulate spike firing, thus
      altering the neuronal input-output relationships in a process called long-term
      potentiation of intrinsic excitability (LTP-IE). Here, the intracellular signals
      that mediate this D1/5 receptor-dependent LTP-IE were determined using whole cell
      current-clamp recordings in layer V/VI rat pyramidal neurons from PFC slices.
      After blockade of all major amino acid receptors (V(hold) = -65 mV) brief tetanic
      stimulation (20 Hz) of local afferents or application of the D1 agonist SKF81297
      (0.2-50 microM) induced LTP-IE, as shown by a prolonged (>40 min) increase in
      depolarizing pulse-evoked spike firing. Pretreatment with the D1/5 antagonist
      SCH23390 (1 microM) blocked both the tetani- and D1/5 agonist-induced LTP-IE,
      suggesting a D1/5 receptor-mediated mechanism. The SKF81297-induced LTP-IE was
      significantly attenuated by Cd(2+), [Ca(2+)](i) chelation, by inhibition of
      phospholipase C, protein kinase-C, and Ca(2+)/calmodulin kinase-II, but not by
      inhibition of adenylate cyclase, protein kinase-A, MAP kinase, or L-type Ca(2+)
      channels. Thus this form of D1/5 receptor-mediated LTP-IE relied on Ca(2+) influx
      via non-L-type Ca(2+) channels, activation of PLC, intracellular Ca(2+)
      elevation, activation of Ca(2+)-dependent CaMKII, and PKC to mediate modulation
      of voltage-dependent ion channel(s). This D1/5 receptor-mediated modulation by
      PKC coexists with the previously described PKA-dependent modulation of K(+) and
      Ca(2+) currents to dynamically regulate overall excitability of PFC neurons.

PMID- 17229831
TI  - In vitro activity of tigecycline against carbapenem-susceptible and -resistant
      isolates of Klebsiella spp. and Enterobacter spp.

PMID- 17229832
TI  - Antibiotic efflux pumps in Gram-negative bacteria: the inhibitor response
      strategy.
AB  - After several decades of continuously successful antibiotic therapy against
      bacterial infections, we are now facing a worrying prospect: the accelerated
      evolution of antibiotic resistance to important human pathogens and the scarcity
      of new anti-infective drug families under development. Efflux is a general
      mechanism responsible for bacterial resistance to antibiotics. This active drug
      transport is involved in low intrinsic susceptibility, cross-resistance to
      chemically unrelated classes of molecules, and selection/acquisition of
      additional mechanisms of resistance. Thus, inhibition of bacterial efflux
      mechanisms appears to be a promising target in order to (i) increase the
      intracellular concentration of antibiotics that are expelled by efflux pumps,
      (ii) restore the drug susceptibility of resistant clinical strains, and (iii)
      reduce the capability for acquired additional resistance. Structurally unrelated
      classes of efflux pump inhibitors (EPIs) have been described and tested in the
      last decade, including some analogues of antibiotic substrates and new chemical
      molecules. Among the current collection of EPIs, only a few compounds have been
      studied taking into account the structure-activity relationships and the spectrum
      of activity in terms of antibiotics, pumps and bacteria. While large efforts have
      characterized an increasing number of bacterial efflux pumps and generated
      several potentially active EPIs, they have not elucidated the molecular basis of
      efflux transport and inhibition. Recent studies of pump-substrate complexes, the
      3D resolution of the efflux pumps, the synthesis of novel compounds and molecular
      dynamic studies may generate new clues to decipher and select novel targets
      inside the efflux mechanisms and, finally, may result in a clinically useful
      molecule.

PMID- 17229833
TI  - Commentary: Assessing the effects of the Scottish Smokefree Law--the placebo
      effect and the importance of obtaining unbiased data.

PMID- 17229834
TI  - Increased apoptosis, p53 up-regulation, and cerebellar neuronal degeneration in
      repair-deficient Cockayne syndrome mice.
AB  - Cockayne syndrome (CS) is a rare recessive childhood-onset neurodegenerative
      disease, characterized by a deficiency in the DNA repair pathway of transcription
      coupled nucleotide excision repair. Mice with a targeted deletion of the CSB gene
      (Csb-/-) exhibit a much milder ataxic phenotype than human patients. Csb-/- mice
      that are also deficient in global genomic repair [Csb-/-/xeroderma pigmentosum C
      (Xpc)-/-] are more profoundly affected, exhibiting whole-body wasting, ataxia,
      and neural loss by postnatal day 21. Cerebellar granule cells demonstrated high
      TUNEL staining indicative of apoptosis. Purkinje cells, identified by the marker
      calbindin, were severely depleted and, although not TUNEL-positive, displayed
      strong immunoreactivity for p53, indicating cellular stress. A subset of animals
      heterozygous for Csb and Xpc deficiencies was more mildly affected, demonstrating
      ataxia and Purkinje cell loss at 3 months of age. Mouse, Csb-/-, and Xpc-/-
      embryonic fibroblasts each exhibited increased sensitivity to UV light, which
      generates bulky DNA damage that is a substrate for excision repair. Whereas Csb-/
      /Xpc-/- fibroblasts were more UV-sensitive than either single knockout, double
      heterozygote fibroblasts had normal UV sensitivity. Csb-/- mice crossed with a
      strain defective in base excision repair (Ogg1) demonstrated no enhanced
      neurodegenerative phenotype. Complete deficiency in nucleotide excision repair
      therefore renders the brain profoundly sensitive to neurodegeneration in specific
      cell types of the cerebellum, possibly because of unrepaired endogenous DNA
      damage that is a substrate for nucleotide but not base excision repair.

PMID- 17229835
TI  - New Paleocene skeletons and the relationship of plesiadapiforms to crown-clade
      primates.
AB  - Plesiadapiforms are central to studies of the origin and evolution of primates
      and other euarchontan mammals (tree shrews and flying lemurs). We report results
      from a comprehensive cladistic analysis using cranial, postcranial, and dental
      evidence including data from recently discovered Paleocene plesiadapiform
      skeletons (Ignacius clarkforkensis sp. nov.; Dryomomys szalayi, gen. et sp.
      nov.), and the most plesiomorphic extant tree shrew, Ptilocercus lowii. Our
      results, based on the fossil record, unambiguously place plesiadapiforms with
      Euprimates and indicate that the divergence of Primates (sensu lato) from other
      euarchontans likely occurred before or just after the Cretaceous/Tertiary
      boundary (65 Mya), notably later than logistical model and molecular estimates.
      Anatomical features associated with specialized pedal grasping (including a nail
      on the hallux) and a petrosal bulla likely evolved in the common ancestor of
      Plesiadapoidea and Euprimates (Euprimateformes) by 62 Mya in either Asia or North
      America. Our results are consistent with those from recent molecular analyses
      that group Dermoptera with Scandentia. We find no evidence to support the
      hypothesis that any plesiadapiforms were mitten-gliders or closely related to
      Dermoptera.

PMID- 17229836
TI  - Patients with hippocampal amnesia cannot imagine new experiences.
AB  - Amnesic patients have a well established deficit in remembering their past
      experiences. Surprisingly, however, the question as to whether such patients can
      imagine new experiences has not been formally addressed to our knowledge. We
      tested whether a group of amnesic patients with primary damage to the hippocampus
      bilaterally could construct new imagined experiences in response to short verbal
      cues that outlined a range of simple commonplace scenarios. Our results revealed
      that patients were markedly impaired relative to matched control subjects at
      imagining new experiences. Moreover, we identified a possible source for this
      deficit. The patients' imagined experiences lacked spatial coherence, consisting
      instead of fragmented images in the absence of a holistic representation of the
      environmental setting. The hippocampus, therefore, may make a critical
      contribution to the creation of new experiences by providing the spatial context
      into which the disparate elements of an experience can be bound. Given how
      closely imagined experiences match episodic memories, the absence of this
      function mediated by the hippocampus, may also fundamentally affect the ability
      to vividly re-experience the past.

PMID- 17229837
TI  - Identification of Rab11 as a small GTPase binding protein for the Evi5 oncogene.
AB  - The Evi5 oncogene has recently been shown to regulate the stability and
      accumulation of critical G(1) cell cycle factors including Emi1, an inhibitor of
      the anaphase-promoting complex/cyclosome, and cyclin A. Sequence analysis of the
      amino terminus of Evi5 reveals a Tre-2, Bub2, Cdc16 domain, which has been shown
      to be a binding partner and GTPase-activating protein domain for the Rab family
      of small Ras-like GTPases. Here we describe the identification of Evi5 as a
      candidate binding protein for Rab11, a GTPase that regulates intracellular
      transport and has specific roles in endosome recycling and cytokinesis. By yeast
      two-hybrid analysis, immunoprecipitation, and Biacore analysis, we demonstrate
      that Evi5 binds Rab11a and Rab11b in a GTP-dependent manner. However, Evi5
      displays no activation of Rab11 GTPase activity in vitro. Evi5 colocalizes with
      Rab11 in vivo, and overexpression of Rab11 perturbs the localization of Evi5,
      redistributing it into Rab11-positive recycling endosomes. Interestingly, in
      vitro binding studies show that Rab11 effector proteins including FIP3 compete
      with Evi5 for binding to Rab11, suggesting a partitioning between Rab11-Evi5 and
      Rab11 effector complexes. Indeed, ablation of Evi5 by RNA interference causes a
      mislocalization of FIP3 at the abscission site during cytokinesis. These data
      demonstrate that Evi5 is a Rab11 binding protein and that Evi5 may cooperate with
      Rab11 to coordinate vesicular trafficking, cytokinesis, and cell cycle control
      independent of GTPase-activating protein function.

PMID- 17229838
TI  - DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to
      CD8+ T cells in a spectrum of human MHC I haplotypes.
AB  - Optimal HIV vaccines should elicit CD8+ T cells specific for HIV proteins
      presented on MHC class I products, because these T cells contribute to host
      resistance to viruses. We had previously found that the targeting of antigen to
      dendritic cells (DCs) in mice efficiently induces CD8+ T cell responses. To
      extend this finding to humans, we introduced the HIV p24 gag protein into a mAb
      that targets DEC-205/CD205, an endocytic receptor of DCs. We then assessed cross
      presentation, which is the processing of nonreplicating internalized antigen onto
      MHC class I for recognition by CD8+ T cells. Low doses of alphaDEC-gag, but not
      control Ig-gag, stimulated proliferation and IFN-gamma production by CD8+ T cells
      isolated from the blood of HIV-infected donors. alphaCD205 fusion mAb was more
      effective for cross-presentation than alphaCD209/DC-SIGN, another abundant DC
      uptake receptor. Presentation was diverse, because we identified eight different
      gag peptides that were recognized via DEC-205 in 11 individuals studied
      consecutively. Our results, based on humans with highly polymorphic MHC products,
      reveal that DCs and DEC-205 can cross-present several different peptides from a
      single protein. Because of the consistency in eliciting CD8+ T cell responses,
      these data support the testing of alphaDEC-205 fusion mAb as a protein-based
      vaccine.

PMID- 17229839
TI  - Childhood maltreatment predicts adult inflammation in a life-course study.
AB  - Stress in early life has been associated with insufficient glucocorticoid
      signaling in adulthood, possibly affecting inflammation processes. Childhood
      maltreatment has been linked to increased risk of adult disease with potential
      inflammatory origin. However, the impact of early life stress on adult
      inflammation is not known in humans. We tested the life-course association
      between childhood maltreatment and adult inflammation in a birth cohort followed
      to age 32 years as part of the Dunedin Multidisciplinary Health and Development
      Study. Regression models were used to estimate the effect of maltreatment on
      inflammation, adjusting for co-occurring risk factors and potential mediating
      variables. Maltreated children showed a significant and graded increase in the
      risk for clinically relevant C-reactive protein levels 20 years later, in
      adulthood [risk ratio (RR)=1.80, 95% confidence interval (CI)=1.26-2.58]. The
      effect of childhood maltreatment on adult inflammation was independent of the
      influence of co-occurring early life risks (RR=1.58, 95% CI=1.08-2.31), stress in
      adulthood (RR=1.64, 95% CI=1.12-2.39), and adult health and health behavior
      (RR=1.76, 95% CI=1.23-2.51). More than 10% of cases of low-grade inflammation in
      the population, as indexed by high C-reactive protein, may be attributable to
      childhood maltreatment. The association between maltreatment and adult
      inflammation also generalizes to fibrinogen and white blood cell count. Childhood
      maltreatment is a previously undescribed, independent, and preventable risk
      factor for inflammation in adulthood. Inflammation may be an important
      developmental mediator linking adverse experiences in early life to poor adult
      health.

PMID- 17229840
TI  - Color naming reflects optimal partitions of color space.
AB  - The nature of color categories in the world's languages is contested. One major
      view holds that color categories are organized around universal focal colors,
      whereas an opposing view holds instead that categories are defined at their
      boundaries by linguistic convention. Both of these standardly opposed views are
      challenged by existing data. Here, we argue for a third view based on a proposal
      by Jameson and D'Andrade [Jameson KA, D'Andrade RG (1997) in Color Categories in
      Thought and Language, eds Hardin CL, Maffi L (Cambridge Univ Press, Cambridge,
      U.K.), pp 295-319]: that color naming across languages reflects optimal or near
      optimal divisions of an irregularly shaped perceptual color space. We formalize
      this idea, test it against color-naming data from a broad range of languages and
      show that it accounts for universal tendencies in color naming while also
      accommodating some observed cross-language variation.

PMID- 17229841
TI  - Low-dose L-arginine administration increases microperfusion of hindlimb muscle
      without affecting blood pressure in rats.
AB  - The objective of this work was to evaluate the influence of exogenous L-arginine
      on the capillary blood flow of peripheral tissues of normotensive subjects. Rats
      were anesthetized with sodium pentobarbital, and the blood flow of femoral,
      dorsal, and ventral skin and gastrocnemius and soleus muscle was measured by
      laser Doppler flow and microsphere methods to compare the blood flow before and
      after the L-arginine infusion. L-arginine lowered the mean blood pressure in a
      dose-dependent manner, but a statistically significant reduction in mean blood
      pressure was detected only at a high dose of 500 mg/kg of body weight. The
      significant blood flow increment was detected after the L-arginine infusion at
      doses of 50 and 150 mg/kg without causing hypotension. Nicardipine, a calcium
      channel blocker, also increased the skin blood flow, but the blood flow increment
      and blood pressure fall were comparable. A significant increment in
      microperfusion was detected in gastrocnemius, soleus muscle, and ventral skin
      compared with control group by the microsphere method. No adverse effects were
      observed during L-arginine and microsphere infusion. The present work indicates
      that l-arginine infusion increases muscle capillary blood flow in rats that are
      not performing exercise. Supplementation with l-arginine might provide additional
      blood flow at rest and during exercise and result in the improvement of muscle
      performance and exercise capacity.

PMID- 17229843
TI  - Beta cells cannot directly prime diabetogenic CD8 T cells in nonobese diabetic
      mice.
AB  - Type 1 diabetes (T1D) is caused by the destruction of insulin-producing islet
      beta cells. CD8 T cells are prevalent in the islets of T1D patients and are the
      major effectors of beta cell destruction in nonobese diabetic (NOD) mice. In
      addition to their critical involvement in the late stages of diabetes, CD8 T
      cells are implicated in the initiation of disease. NOD mice, in which the beta2
      microglobulin gene has been inactivated by gene targeting (NOD.beta2M-/-), have a
      deficiency in CD8 T cells and do not develop insulitis, which suggests that CD8 T
      cells are required for the initiation of T1D. However, neither in humans nor in
      NOD mice have the immunological requirements for diabetogenic CD8 T cells been
      precisely defined. In particular, it is not known in which cell type MHC class I
      expression is required for recruitment and activation of CD8 T cells. Here we
      have generated transgenic NOD mice, which lack MHC class I on mature professional
      antigen-presenting cells (pAPCs). These "class I APC-bald" mice developed
      periislet insulitis but not invasive intraislet insulitis, and they never became
      diabetic. Recruitment to the islet milieu does not therefore require cognate
      interaction between CD8 T cells and MHC class I on mature pAPCs. Conversely, such
      an interaction is critically essential to allow the crucial shift from periislet
      insulitis to invasive insulitis. Importantly, our findings demonstrate
      unequivocally that CD8 T cells cannot be primed to become diabetogenic by islet
      beta cells alone.

PMID- 17229842
TI  - Differences in protein mobility between pioneer versus follower growth cones.
AB  - Navigating growth cones need to integrate, process and respond to guidance
      signals, requiring dynamic information transfer within and between different
      compartments. Studies have shown that, faced with different navigation
      challenges, growth cones display dynamic changes in growth kinetics and
      morphologies. However, it remains unknown whether these are paralleled by
      differences in their internal molecular dynamics. To examine whether there are
      protein mobility differences during guidance, we developed multiphoton
      fluorescence recovery after photobleaching methods to determine molecular
      diffusion rates in pathfinding growth cones in vivo. Actively navigating growth
      cones (leaders) have consistently longer recovery times than growth cones that
      are fasciculated and less actively navigating (followers). Pharmacological
      perturbations of the cytoskeleton point to actin as the primary modulator of
      diffusion in differently behaving growth cones. This approach provides a powerful
      means to quantify mobility of specific proteins in neurons in vivo and reveals
      that diffusion is important during axon navigation.

PMID- 17229844
TI  - Directional shear flow and Rho activation prevent the endothelial cell apoptosis
      induced by micropatterned anisotropic geometry.
AB  - To study the roles of anisotropic cell morphology and directionality of
      mechanical force in apoptosis, the spreading of human umbilical vein endothelial
      cells (HUVECs) was constrained by growing on micropatterned (MP) strips of
      fibronectin (FN, 20 microg/cm2) with widths of 15, 30, and 60 microm on silicone
      membrane. Cells on 30- and 60-microm strips, like cells on a nonpatterned (NP)
      surface coated with FN, showed clear actin stress fibers with anchoring spots of
      phosphorylated focal adhesion kinase (p-FAK) and no significant apoptosis. On 15
      microm strips, cells had few stress fibers, no p-FAK, and significant apoptosis.
      After seeding for 12 h, the cells were subjected to pulsatile shear stress (12+/
      4 dyn/cm2) parallel or perpendicular to MP strips, or kept under static
      condition. Parallel flow caused cell elongation with enhanced stress fibers and p
      FAK, and a reduction in apoptosis, but perpendicular flow did not. The Rho
      inhibitory C3 exoenzyme abolished the effects of parallel flow. RhoV14, the
      constitutively active Rho, enhanced stress fibers and p-FAK, and prevented
      apoptosis of HUVECs on 15-microm strips under static condition. RhoV14 also
      reduced cell apoptosis under both parallel and perpendicular flows. Our results
      indicate that cell apoptosis can be modulated by changes in ECM micropatterning,
      anisotropic cell morphology, and mechanical forces. These extracellular
      microenvironment factors affect cell survival through alterations in Rho GTPase
      activity, stress fiber organization, and FAK phosphorylation.

PMID- 17229845
TI  - FSTL3 deletion reveals roles for TGF-beta family ligands in glucose and fat
      homeostasis in adults.
AB  - Activin and myostatin are related members of the TGF-beta growth factor
      superfamily. FSTL3 (Follistatin-like 3) is an activin and myostatin antagonist
      whose physiological role in adults remains to be determined. We found that
      homozygous FSTL3 knockout adults developed a distinct group of metabolic
      phenotypes, including increased pancreatic islet number and size, beta cell
      hyperplasia, decreased visceral fat mass, improved glucose tolerance, and
      enhanced insulin sensitivity, changes that might benefit obese, insulin-resistant
      patients. The mice also developed hepatic steatosis and mild hypertension but
      exhibited no alteration of muscle or body weight. This combination of phenotypes
      appears to arise from increased activin and myostatin bioactivity in specific
      tissues resulting from the absence of the FSTL3 antagonist. Thus, the enlarged
      islets and beta cell number likely result from increased activin action. Reduced
      visceral fat is consistent with a role for increased myostatin action in
      regulating fat deposition, which, in turn, may be partly responsible for the
      enhanced glucose tolerance and insulin sensitivity. Our results demonstrate that
      FSTL3 regulation of activin and myostatin is critical for normal adult metabolic
      homeostasis, suggesting that pharmacological manipulation of FSTL3 activity might
      simultaneously reduce visceral adiposity, increase beta cell mass, and improve
      insulin sensitivity.

PMID- 17229848
TI  - Diagonals of normal operators with finite spectrum.
AB  - Let X={lambda1, ..., lambdaN} be a finite set of complex numbers, and let A be a
      normal operator with spectrum X that acts on a separable Hilbert space H.
      Relative to a fixed orthonormal basis e1, e2, ... for H, A gives rise to a matrix
      whose diagonal is a sequence d=(d1, d2, ...) with the property that each of its
      terms dn belongs to the convex hull of X. Not all sequences with that property
      can arise as the diagonal of a normal operator with spectrum X. The case where X
      is a set of real numbers has received a great deal of attention over the years
      and is reasonably well (though incompletely) understood. In this work we take up
      the case in which X is the set of vertices of a convex polygon in . The critical
      sequences d turn out to be those that accumulate rapidly in X in the sense that
      Sigmainfinityn=1 dist(dn, X)<infinity. We show that there is an abelian group
      GammaX, a quotient of R2 by a countable subgroup with concrete arithmetic
      properties, and a subjective mapping of such sequences d-->s(d)E GammaX with the
      following property: If s(d) not equal 0, then d is not the diagonal of any such
      operator A. We also show that while this is the only obstruction when N=2, there
      are other (as yet unknown) obstructions when N=3.

PMID- 17229846
TI  - Orphan nuclear receptor estrogen-related receptor alpha is essential for adaptive
      thermogenesis.
AB  - Survival of organisms requires the ability to adapt to changes in the
      environment. Adaptation of oxidative metabolism is essential for meeting
      increased energy demands in response to stressors, such as exposure to cold
      temperatures or increased physical activity. Adaptive changes in metabolism are
      often achieved at the level of gene expression, and nuclear receptors have
      prevalent roles in mediating such responses. Estrogen-related receptor alpha
      (ERRalpha) was the first orphan nuclear receptor to be identified, and yet its
      physiologic function remains unknown. Here, we show that mice lacking ERRalpha
      are unable to maintain body temperature when exposed to cold. Surprisingly, the
      inability to adapt to cold is not due to defects in the acute transcriptional
      induction of genes important for thermogenesis. Rather, we show that ERRalpha is
      needed for the high levels of mitochondrial biogenesis and oxidative capacity
      characteristic of brown adipose tissue (BAT), and thus for providing the energy
      necessary for thermogenesis. ERRalpha fulfills this role by acting directly at
      genes important for mitochondrial function, parallel to other factors controlling
      mitochondrial gene expression, such as NRF1 and NRF2/GABPA. Our findings
      demonstrate that ERRalpha is a key regulator of mitochondrial biogenesis and
      oxidative metabolism, and essential for adaptive thermogenesis.

PMID- 17229847
TI  - Replication is required for the RecA localization response to DNA damage in
      Bacillus subtilis.
AB  - In both prokaryotes and eukaryotes, proteins involved in DNA repair often
      organize into multicomponent complexes that can be visualized as foci in living
      cells. We used a RecA-GFP fusion to examine the subcellular cues that direct RecA
      GFP to assemble as foci in response to DNA damage. We used two different methods
      to inhibit initiation of DNA replication and determined that DNA replication is
      required for the cell to establish RecA-GFP foci after exposure to DNA-damaging
      agents. Furthermore, use of endonuclease cleavage to generate a site-specific
      double-strand break demonstrated that the replication machinery (replisome) and
      DNA synthesis are required for assembly of RecA-GFP foci during repair of a
      double-strand break. We monitored the cellular levels of RecA and found that
      focus formation does not require further induction of protein levels, suggesting
      that foci result from a redistribution of existing protein to sites of damage
      encountered by the replisome. Taken together, our results support the model that
      existing RecA protein is recruited to ssDNA generated by the replisome at sites
      of DNA damage. These results provide insight into the mechanisms that the cell
      uses to recruit repair proteins to damaged DNA in living cells.

PMID- 17229849
TI  - Continuous polyelectrolyte adsorption under an applied electric potential.
AB  - Interactions between charged macromolecules (e.g., proteins, nucleic acids,
      polyelectrolytes) and charged surfaces govern many natural and industrial
      processes. We investigate here the influence of an applied electric potential on
      the adsorption of charged polymers, and report the following significant result:
      the adsorption of certain amine side chain-containing polycations may become
      continuous, i.e., asymptotically linear (or nearly linear) in time over hours,
      upon the application of a modest anodic potential. Employing optical waveguide
      lightmode spectroscopy (OWLS) and an indium tin oxide (ITO) substrate, we show
      that asymptotic kinetics, and the adsorbed mass at the onset of the asymptotic
      regime, depend sensitively on polymer chemistry (in particular, side chain volume
      and charge location), increase with applied potential and ionic strength
      (conditions favoring a thicker initial layer), and are independent of bulk
      polymer concentration (suggesting postadsorption events to be rate limiting). X
      ray photoelectron spectra reveal a suppressed polymer charge within layers formed
      via continuous adsorption, but no evidence of electrochemical reactions. We
      propose a mechanism based on polymer-polymer binding within the adsorbed layer,
      enabled by suppressed electrostatic repulsion and/or enhanced ionic correlations
      near the conducting surface, and stabilized by short-range attractive
      interactions. Continuous adsorption under an applied electric potential offers
      the possibility of nanoscale films of tailored polymer content realized in a
      single step.

PMID- 17229850
TI  - Antibody to human leukocyte antigen triggers endothelial exocytosis.
AB  - Although antibodies to HLA play a role in the pathogenesis of diseases processes
      such as rejection of transplanted organs, the precise mechanisms by which
      antibodies cause tissue injury are not completely understood. We hypothesized
      that antibodies to host tissues cause inflammation in part by activating
      endothelial exocytosis of granules that contain prothrombotic mediators such as
      von Willebrand Factor (VWF) and proinflammatory mediators such as P-selectin. To
      test this hypothesis, we treated human endothelial cells with murine monoclonal
      antibody W6/32 to HLA class I and then measured exocytosis by the release of VWF
      and the externalization of P-selectin. Antibody to HLA activates endothelial
      exocytosis in a dose-dependent manner over time. The biologically active
      complement split product, C5a, adds a slight but significant increase to antibody
      induction of exocytosis. Antibody to HLA alone or with C5a did not damage the
      cells. Cross-linking of HLA appears to play a role in the ability of antibody to
      activate exocytosis, because the W6/32 monovalent Fab fragment did not activate
      VWF release, but the bivalent Fab'2 was effective in triggering exocytosis. To
      explore the in vivo effects of antibody upon graft injury, we infused W6/32 Fab'2
      antibody to human HLA into severe combined immunodeficient/beige mice that had
      been transplanted with human skin grafts. Antibody to HLA activated exocytosis
      and inflammation in human skin grafts. Our data show that antibody to host
      antigens can activate human endothelial cell exocytosis and leukocyte
      trafficking. By triggering vascular inflammation, antibody activation of
      exocytosis may play a role in transplant rejection.

PMID- 17229851
TI  - A proposal for robust temperature compensation of circadian rhythms.
AB  - The internal circadian rhythms of cells and organisms coordinate their
      physiological properties to the prevailing 24-h cycle of light and dark on earth.
      The mechanisms generating circadian rhythms have four defining characteristics:
      they oscillate endogenously with period close to 24 h, entrain to external
      signals, suffer phase shifts by aberrant pulses of light or temperature, and
      compensate for changes in temperature over a range of 10 degrees C or more. Most
      theoretical descriptions of circadian rhythms propose that the underlying
      mechanism generates a stable limit cycle oscillation (in constant darkness or dim
      light), because limit cycles quite naturally possess the first three defining
      properties of circadian rhythms. On the other hand, the period of a limit cycle
      oscillator is typically very sensitive to kinetic rate constants, which increase
      markedly with temperature. Temperature compensation is therefore not a general
      property of limit cycle oscillations but must be imposed by some delicate balance
      of temperature dependent effects. However, "delicate balances" are unlikely to be
      robust to mutations. On the other hand, if circadian rhythms arise from a
      mechanism that concentrates sensitivity into a few rate constants, then the
      "balancing act" is likely to be more robust and evolvable. We propose a switch
      like mechanism for circadian rhythms that concentrates period sensitivity in just
      two parameters, by forcing the system to alternate between a stable steady state
      and a stable limit cycle.

PMID- 17229852
TI  - Is throat screening necessary to detect methicillin-resistant Staphylococcus
      aureus colonization in patients upon admission to an intensive care unit?

PMID- 17229853
TI  - Intrarenal abscesses due to Ureaplasma urealyticum in a transplanted kidney.
AB  - A young woman developed multiple abscesses in her transplanted kidney.
      Amplification of the 16S rRNA gene with subsequent sequencing revealed Ureaplasma
      urealyticum as the infectious agent. Microbiological diagnosis and sensitivity
      testing led to therapy with levofloxacin, resulting in rapid recovery of the
      patient.

PMID- 17229854
TI  - Mutated G4P[8] rotavirus associated with a nationwide outbreak of gastroenteritis
      in Nicaragua in 2005.
AB  - During February and March 2005, one of the largest national recorded outbreaks of
      severe acute gastroenteritis occurred in Nicaragua, affecting >or=64,000
      individuals and causing >or=56 deaths, predominantly in children under 5 years of
      age. Through a nationwide laboratory-based study, stool samples were collected
      and investigated for rotavirus. Of 108 stool samples examined, 72 (67%) were
      positive for rotavirus. While 69% (50/72) of the positive samples were found in
      children less than 2 years of age, 50% (6/12) of the adult samples were positive.
      A mutated G4P[8] strain was the most commonly recognized strain (85%), followed
      by mixed G strains (8%) and G9P[8] (7%) strains. Phylogenetic analysis of the VP7
      gene revealed that the G4 strains belonged to the emerging lineage Ic and was
      distantly related to the ST3 and VA70 G4 strains. Secondary structure predictions
      of the VP7 G4 protein revealed an insert of an asparagine residue in position 76,
      which, combined with additional mutations, surprisingly modified two downstream
      beta-sheets at amino acid positions 80 to 85 and 115 to 119. The 2005 G4P[8]
      strain compared to a G4P[8] strain from 2002 had a substitution of an asparagine
      residue for threonine (Asn-->Thr) at position 96 within antigenic region A, thus
      eliminating a potential glycosylation site. The mutated G4 virus was introduced
      in Nicaragua after 2002 and probably emerged from Brazil, Argentina, or Uruguay.

PMID- 17229855
TI  - Evaluation of combined general primer-mediated PCR sequencing and type-specific
      PCR strategies for determination of human papillomavirus genotypes in cervical
      cell specimens.
AB  - A strategy combining human papillomavirus general primer (mainly the PGMY
      primers)-directed PCR sequencing and type-specific PCR is presented. DNA samples
      were first tested in general primer-mediated PCR. The amplified fragments of
      positive samples after ethidium bromide-stained DNA gel analysis were further
      sequenced, and corresponding DNA samples were further analyzed by PCR using type
      specific primers for human papillomavirus (HPV) types 16, 18, 31, and 52. The
      comparison of the results of 157 samples analyzed by this strategy in parallel
      with the Hybrid Capture 2 tests and with the HPV INNO-LiPA (Innogenetics line
      probe assay) shows that this method is suitable for HPV detection and genotyping
      in cervical cell samples. Although the PCR sequencing method is as sensitive as
      the HPV INNO-LiPA for HPV detection, our method allows the identification of a
      broader range of HPV types. In contrast, the HPV INNO-LiPA was less time
      consuming and better identified coinfections.

PMID- 17229856
TI  - Quantitative detection and rapid identification of human adenoviruses.
AB  - We have established a method of quantitative detection and rapid identification
      of human adenoviruses (hAdVs). Using LightCycler PCR with a primer set, we were
      able to amplify 554 bp of the hexon gene from each of 51 prototype strains of
      hAdVs. The sensitivity of LightCycler PCR was 10 copies of hAdV DNA/reaction.
      When LightCycler PCR was performed using a set of primers, hAdV was positive for
      74.4% (99 of 133) of conjunctivitis patients and for 27.3% (81 of 297) of
      respiratory infection patients. We also attempted to measure hAdV in the
      potentially contaminated eye drops used by patients, detecting 5.4 x 10(2) to 1.6
      x 10(6) copies/ml of hAdV. We determined the 350-bp nucleotide sequence of the
      amplified hexon gene and compared it with the sequences of the 51 prototype
      strains. Phylogenetic analysis based on 350 bp of the hexon gene identified 99
      positive conjunctival swabs as 24 cases of AdV type 3 (AdV-3), 14 cases of AdV-4,
      1 case of AdV-8, 19 cases of AdV-19a, and 41 cases of AdV-37. The 81 sequences
      from pharyngeal or nasal mucus swabs were identified as 29 cases of AdV-2, 18
      cases of AdV-1, 18 cases of AdV-5, 12 cases of AdV-4, 2 cases of AdV-37, 1 case
      of AdV-3, and 1 case of AdV-6. LightCycler PCR followed by phylogenetic analysis
      provides an effective tool for the rapid identification of hAdVs and for studying
      molecular epidemiology.

PMID- 17229857
TI  - Use of capillary blood samples as a new approach for diagnosis of Dengue virus
      infection.
AB  - We evaluated the use of capillary blood samples stored on filter papers for
      diagnosis of dengue virus infection. Venous and capillary blood samples were
      collected from 130 patients suspected of having dengue fever. We compared the
      performances of standard reference methods using capillary blood samples absorbed
      onto filter papers versus venous blood samples. The resulting sensitivity,
      specificity, and positive predictive value of tests performed on filter paper
      compared to those performed on venous blood samples were 81.6% (62/76; 95%
      confidence interval [CI], 74.9% to 88.3%), 90.7% (49/54; 95% CI, 85.7% to 95.7%),
      and 92.5% (62/67; 95% CI, 86.2% to 98.8%), respectively. During the acute phase
      of dengue virus infection (day 1 to day 4), the tests performed on capillary
      blood samples had a sensitivity of 88.5% (95% CI, 82.0% to 95.0%) and a
      specificity of 93.8% (95% CI, 88.9% to 98.7%). During the convalescent phase of
      infection, this method allowed the viral serotype to be determined for 4 of 15
      (27%) dengue virus-infected patients for whom virological diagnosis using venous
      samples was negative. Capillary blood samples could therefore be a good
      alternative for the diagnosis of dengue virus infection in tropical areas.
      Indeed, these samples are convenient for storage and transport without the need
      for a cold chain and simplify the collection of samples from children. Moreover,
      our results suggest that viral particles persist longer in capillary blood than
      in peripheral blood. Analysis of the viability of viral particles under these
      conditions may give new insights into the physiopathology of dengue virus
      infection and the transmission of dengue virus during outbreaks.

PMID- 17229858
TI  - COBAS AmpliPrep-COBAS TaqMan hepatitis B virus (HBV) test: a novel automated real
      time PCR assay for quantification of HBV DNA in plasma.
AB  - Success in antiviral therapy for chronic hepatitis B is supported by highly
      sensitive PCR-based assays for hepatitis B virus (HBV) DNA. Nucleic acid
      extraction from biologic specimens is technically demanding, and reliable PCR
      results depend on it. The performances of the fully automatic system COBAS
      AmpliPrep-COBAS TaqMan 48 (CAP-CTM; Roche, Branchburg, NJ) for HBV DNA extraction
      and real-time PCR quantification were assessed and compared to the endpoint PCR
      COBAS AMPLICOR HBV monitor (CAHBM; Roche). Analytical evaluation with a
      proficiency panel showed that CAP-CTM quantitated HBV DNA levels in one single
      run over a wide dynamic range (7 logs) with a close correlation between expected
      and observed values (r = 0.976, interassay variability below 5%). Clinical
      evaluation, as tested with samples from 92 HBsAg-positive patients, demonstrated
      excellent correlation with CAHBM (r = 0.966, mean difference in quantitation =
      0.36 log(10) IU/ml). CAP-CTM detected 10% more viremic patients and longer
      periods of residual viremia in those on therapy. In lamivudine (LAM)-resistant
      patients, the reduction of HBV DNA after 12 months of Adefovir (ADF) was higher
      in the combination (LAM+ADF) schedule than in ADF monotherapy (5.1 logs versus
      3.5 logs), suggesting a benefit in continuing LAM. CAP-CTM detected HBV DNA in
      liver biopsy samples from 15% of HBsAg-negative, anti-HBcAg-positive graft donors
      with no HBV DNA in plasma. The amount of intrahepatic HBV DNA was significantly
      lower in occult HBV infection than in overt disease. CAP-CTM can improve the
      management of HBV infection and the assessment of antiviral therapy and drug
      resistance, supporting further insights in the emerging area of occult HBV
      infection.

PMID- 17229859
TI  - Generic detection of coronaviruses and differentiation at the prototype strain
      level by reverse transcription-PCR and nonfluorescent low-density microarray.
AB  - A nonfluorescent low-cost, low-density oligonucleotide array was designed for
      detecting the whole coronavirus genus after reverse transcription (RT)-PCR. The
      limit of detection was 15.7 copies/reaction. The clinical detection limit in
      patients with severe acute respiratory syndrome was 100 copies/sample. In 39
      children suffering from coronavirus 229E, NL63, OC43, or HKU1, the sensitivity
      was equal to that of individual real-time RT-PCRs.

PMID- 17229860
TI  - Intimin types determined by heteroduplex mobility assay of intimin gene (eae)
      positive Escherichia coli strains.
AB  - We developed a quick genetic approach to screen variants of the intimin gene
      (eae) by using a heteroduplex mobility assay (HMA) that targets the 5' conserved
      region of eae. The eae variants were categorized into 4 major HMA types and 10
      minor subtypes.

PMID- 17229861
TI  - Real-time PCR diagnostics failure caused by nucleotide variability within exon 4
      of the human cytomegalovirus major immediate-early gene.
AB  - Here we report how variability in the human cytomegalovirus genome sequence may
      seriously affect the outcome of its molecular diagnosis. A real-time quantitative
      PCR assay targeting the major immediate-early gene failed to detect the viral
      load in some, but not all, clinical samples from hematooncological patients. By
      amplification and sequencing the DNA across the regions targeted by this assay we
      found a number of nucleotide substitutions which accounted for decreased
      primer/probe binding. This decreased the sensitivity of the assay up to 1,000
      fold.

PMID- 17229862
TI  - Evidence for a pseudo-outbreak of Candida guilliermondii fungemia in a university
      hospital in Brazil.
AB  - Fungal infections due to Candida species represent an important cause of
      nosocomial bloodstream infections. We report a large pseudo-outbreak of Candida
      guilliermondii fungemia that occurred in a university hospital in Brazil. C.
      guilliermondii was identified in 64 (43%) of the 149 blood samples drawn between
      June 2003 and July 2004. The samples were from patients in different wards of the
      hospital but concentrated in pediatric units. None of the patients had clinical
      signs of fungemia, and observational analysis revealed errors in the collection
      of blood samples. During the investigation of the pseudo-outbreak, C.
      guilliermondii was isolated from environmental surfaces and from the skin and
      nails of members of the nursing team. Through a subtyping analysis it was found
      that some of the nonpatient isolates were highly related to the patient isolates,
      and all the patient isolates were highly related. This is consistent with the
      hypothesis that the pseudo-outbreak was from a limited number of common sources.
      The adoption of intervention measures was effective in resolving the outbreak,
      supporting the hypothesis that the outbreak was due to poor techniques of drawing
      blood samples for culture.

PMID- 17229863
TI  - Monitoring of hepatitis C virus quasispecies in chronic infection by matrix
      assisted laser desorption ionization-time of flight mass spectrometry mutation
      detection.
AB  - Using both a mass spectrometry-based method and the classical method of cloning
      and sequencing, we demonstrated weekly changes in the hypervariable region 1
      quasispecies of a chimpanzee infected with an infectious clone, coinciding with
      neutralizing antibody emergence. We also used the mass spectrometry method in the
      clinical follow-up of a chronically infected patient over a 5-year period.

PMID- 17229864
TI  - PCR detection of Entamoeba histolytica, Entamoeba dispar, and Entamoeba
      moshkovskii in stool samples from Sydney, Australia.
AB  - This study investigated the presence of Entamoeba histolytica, Entamoeba dispar,
      and Entamoeba moshkovskii in stool samples from a patient population in Sydney,
      Australia. Stool samples were tested by microscopy and PCR. Five patients were
      found with E. histolytica infections, while E. dispar and E. moshkovskii were
      observed in 63 (70.8%) and 55 (61.8%) patients, respectively, by PCR. This is the
      first study in Australia using molecular techniques to determine the presence of
      E. histolytica, E. dispar, and E. moshkovskii.

PMID- 17229865
TI  - Application of rrs gene sequencing to elucidate the clinical significance of
      Eggerthela lenta infection.

PMID- 17229866
TI  - Human herpesvirus 6 DNA levels in cerebrospinal fluid due to primary infection
      differ from those due to chromosomal viral integration and have implications for
      diagnosis of encephalitis.
AB  - The prevalence and concentration of human herpesvirus 6 (HHV-6) DNA in the
      cerebrospinal fluid (CSF) of the immunocompetent in primary infection was
      compared with that in viral chromosomal integration. Samples from 510 individuals
      with suspected encephalitis, 200 young children and 310 older children and/or
      adults, and 12 other patients were tested. HHV-6 DNA concentration (log(10)
      copies/ml) was measured in CSF, serum, and whole blood using PCR. Serum HHV-6
      immunoglobulin G antibody was measured by indirect immunofluorescence. Primary
      infection was defined by antibody seroconversion and/or a low concentration of
      HHV-6 DNA (<3.0 log(10) copies/ml) in a seronegative serum. Chromosomal
      integration was defined by a high concentration of viral DNA in serum (>/=3.5
      log(10) copies/ml) or whole blood (>/=6.0 log(10) copies/ml). The prevalences of
      CSF HHV-6 DNA in primary infection and chromosomal integration were 2.5% and
      2.0%, respectively, in the young children (<2 years) and 0% and 1.3%,
      respectively, in the older children and/or adults. The mean concentration of CSF
      HHV-6 DNA in 9 children with primary infection (2.4 log(10) copies/ml) was
      significantly lower than that of 21 patients with viral chromosomal integration
      (4.0 log(10) copies/ml). Only HHV-6B DNA was found in primary infection, whereas
      in viral integration, 4 patients had HHV-6A and 17 patients HHV-6B. Apart from
      primary infection, chromosomal integration is the most likely cause of HHV-6 DNA
      in the CSF of the immunocompetent. Our results show that any diagnosis of HHV-6
      encephalitis or other type of active central nervous system infection should not
      be made without first excluding chromosomal HHV-6 integration by measuring DNA
      load in CSF, serum, and/or whole blood.

PMID- 17229867
TI  - Accuracies of beta-lactam susceptibility test results for Pseudomonas aeruginosa
      with four automated systems (BD Phoenix, MicroScan WalkAway, Vitek, and Vitek 2).
AB  - Contemporary clinical isolates and challenge strains of Pseudomonas aeruginosa
      were tested by four automated susceptibility testing systems (BD Phoenix,
      MicroScan WalkAway, Vitek, and Vitek 2; two laboratories with each) against six
      broad-spectrum beta-lactams, and the results were compared to reference broth
      microdilution (BMD) and to consensus results from three validated methods (BMD,
      Etest [AB Biodisk, Solna, Sweden], and disk diffusion). Unacceptable levels of
      error (minor, major, and very major) were detected, some with systematic biases
      toward false susceptibility (piperacillin-tazobactam and imipenem) and others
      toward false resistance (aztreonam, cefepime, and ceftazidime). We encourage
      corrective action by the system manufacturers to address test biases, and we
      suggest that clinical laboratories using automated systems should consider
      accurate alternative methods for routine use.

PMID- 17229868
TI  - Human papillomavirus quantification in urine and cervical samples by using the
      Mx4000 and LightCycler general real-time PCR systems.
AB  - During the last decade, growing efforts have focused on human papillomavirus
      (HPV) detection using liquid hybridization, conventional PCR, and real-time PCR
      based methods to increase the overall proportion of patients participating in
      cervical cancer screening procedures. We proposed a new general HPV DNA real-time
      PCR on the Mx4000 (Stratagene) and LightCycler (Roche Diagnostics) systems usable
      for both cervical scrape specimens and urine samples. A linear range was obtained
      from 5 DNA copies to 8 log(10) DNA copies/ml, and intra- and interassay
      variations were between 1.8 and 4%. Cervical carcinoma and HPV DNA screening was
      performed in 333 individual women referred for gynecological examination at the
      university hospitals of Angers and Brest and enrolled in the PapU study. Among
      cervical specimens (n = 333), 45% were positive for HPV DNA, with a mean viral
      load at 5.00 log/ml (+/- 1.73). Among urine samples (n = 177), 37% were positive
      with a significant 50-fold-lower mean viral load (3.77 +/- 1.32 log/ml; P <
      0.0001). Kappa agreement for HPV DNA between cervical and urine specimens was
      excellent (93%). Thus, we developed a highly sensitive and quantitative general
      HPV DNA real-time PCR method that allows mass screening of patients with HPV
      infection. The ongoing longitudinal and prospective multicenter PapU study should
      give us the opportunity to validate this method adapted to HPV DNA screening in
      urine samples in a larger population.

PMID- 17229869
TI  - High-throughput screening for small-molecule activators of neutrophils:
      identification of novel N-formyl peptide receptor agonists.
AB  - We screened a chemolibrary of drug-like molecules for their ability to activate
      reactive oxygen species (ROS) production in murine phagocytes, and we identified
      26 novel compounds with potent neutrophil activating properties. We used
      substructure screening, fragment-focusing, and structure-activity relationship
      analyses to further probe the parent library and defined at least two groups of
      activators of ROS production in murine neutrophils: t-butyl benzene and thiophene
      2-amide-3-carboxylic ester derivatives. Further studies of the active compounds
      revealed 11 compounds that activated ROS production in human neutrophils, and six
      of these compounds also activated intercellular Ca(2+) mobilization and
      chemotaxis in human neutrophils. Of the latter compounds, compound 14 (1,3
      benzodioxolane-5-carboxylic acid 4'-benzyloxy-3'-methoxybenzylidene-hydrazide)
      activated neutrophils at nanomolar concentrations, and Ca(2+) mobilization was
      inhibited by pertussis toxin and N-t-butoxycarbonyl-Phe-Leu-Phe-Leu-Phe (Boc-2),
      an antagonist of formyl peptide receptors (FPR/FPRL1). Likewise, activation by
      compound 14 was desensitized after N-formyl-Met-Leu-Phe pretreatment. Similar
      biological activities were found for compound 104 (1,3-benzodioxolane-5
      carboxylic acid 3'-bromo-5'-ethoxy-4'-hydroxybenzylidene-hydrazide), an analog of
      compound 14. Furthermore, conformational analysis of the activators of chemotaxis
      and Ca(2+) mobilization showed a high degree of similarity in distances between
      pharmacophore points of compounds 14 and 104 with a model of FPR published by
      Edwards et al. (Mol Pharmacol 68:1301-1310, 2005), indicating that conformational
      features of the agonists identified here are structurally compatible with steric
      constraints of the ligand-binding pocket of the receptor. Based on these results,
      we conclude that compounds 14 and 104 represent novel small-molecule agonists of
      FPR. These studies enhance our understanding of FPR ligand/receptor interactions
      and structure/activity relationships of phagocyte agonists.

PMID- 17229870
TI  - BRCA1 contributes to cell cycle arrest and chemoresistance in response to the
      anticancer agent irofulven.
AB  - Tumor suppressor gene BRCA1 is frequently mutated in familial breast and ovarian
      cancer. BRCA1 plays pivotal roles in maintaining genomic stability by interacting
      with numerous proteins in cell cycle control and DNA repair. Irofulven (6
      hydroxymethylacylfulvene, HMAF, MGI 114, NSC 683863) is one of a new class of
      anticancer agents that are analogs of mushroom-derived illudin toxins.
      Preclinical studies and clinical trials have demonstrated that irofulven is
      effective against several tumor cell types. The exact nature of irofulven-induced
      DNA damage is not completely understood. We demonstrated previously that
      irofulven activates ATM and its targets, NBS1, SMC1, CHK2, and p53. In this
      study, we hypothesize that irofulven induces DNA double-strand breaks and that
      BRCA1 may affect chemosensitivity by controlling cell cycle checkpoints, DNA
      repair, and genomic stability in response to irofulven treatment. We observed
      that irofulven induces the formation of chromosome breaks and radials and the
      activation and foci formation of gamma-H2AX, BRCA1, and RAD51. We also provided
      evidence that irofulven induces the generation of DNA double-strand breaks. By
      using BRCA1-deficient or -proficient cells, we demonstrated that in response to
      irofulven, BRCA1 contributes to the control of S and G(2)/M cell cycle arrest and
      is critical for repairing DNA double-strand breaks and for RAD51-dependent
      homologous recombination. Furthermore, we found that BRCA1 deficiency results in
      increased chromosome damage and chemosensitivity after irofulven treatment.

PMID- 17229871
TI  - Structure-based identification of novel human gamma-glutamylcysteine synthetase
      inhibitors.
AB  - Glutathione depletion represents a potentially important strategy to sensitize
      tumors to cytotoxic drugs. l-Buthionine-(R,S)-sulfoximine (l-BSO) has been
      studied in both preclinical and early clinical trials, but limitation on its
      access has led to a search for alternatives. Using a 3D molecular model of human
      gamma-glutamylcysteine synthetase (gamma-GCS(H)), the major subunit of the rate
      limiting GSH synthetic enzyme, we virtually screened the National Cancer
      Institute chemical database to identify compounds that could bind to and
      potentially inhibit gamma-GCS(H). We identified 51 test chemicals, all with
      structures very distinct from l-BSO. We subjected these compounds to biological
      assays measuring gamma-GCS(H) inhibition and glutathione (GSH) depletion. Among
      10 novel gamma -GCS inhibitors identified, 4 compounds depleted glutathione in
      cells, and 2 with related structures sensitized tumor cells to melphalan
      treatment. This work validates the use of model-based database mining and
      identified inhibitors of gamma-GCS(H) with novel chemical structures.

PMID- 17229872
TI  - Esophageal varices in patients with cirrhosis: multidetector CT esophagography-
      comparison with endoscopy.
AB  - PURPOSE: To evaluate the use of multidetector computed tomographic (CT)
      esophagography to grade esophageal varices and differentiate between varices at
      low risk and those at high risk for bleeding, with endoscopy as the reference
      standard. MATERIALS AND METHODS: This study was approved by the institutional
      review board; all subjects gave informed consent. Ninety patients with cirrhosis
      (65 men, 25 women; mean age, 54.8 years; range, 21-77 years) were prospectively
      enrolled and underwent endoscopy and CT esophagography. Esophageal varices were
      graded independently at endoscopy by two endoscopists. CT esophagograms were
      interpreted retrospectively with a four-point scale by two radiologists blinded
      to other findings. Interobserver agreement between each radiologist and
      endoscopist was determined; endoscopic and CT esophagographic grades of
      esophageal varices were correlated. Radiologist performance for differentiation
      between low- and high-risk varices for bleeding on the basis of morphology at
      endoscopy was evaluated with receiver operating characteristic analysis. Patients
      were interviewed to determine acceptance at both examinations. RESULTS: Thirty
      seven of 90 patients had grade 0, 23 had grade 1, 18 had grade 2, and 12 had
      grade 3 esophageal varices. Thus, 60 patients were determined to be in a low-risk
      group and 30 in a high-risk group for variceal bleeding at endoscopy. There was
      almost perfect agreement in grading esophageal varices between endoscopists.
      There was close correlation (P < .001) and substantial agreement between
      endoscopic and CT esophagographic grades. Radiologist performance for
      differentiating between low- and high-risk varices was 0.931-0.958 (area under
      receiver operating characteristic curve). Patient interview results revealed that
      CT esophagography had better acceptance than did endoscopy (P < .001).
      CONCLUSION: Use of CT esophagography allows grading of esophageal varices and
      differentiation between low- and high-risk varices and shows better patient
      acceptance than does endoscopy.

PMID- 17229873
TI  - Circle of Willis at CT angiography: dose reduction and image quality--reducing
      tube voltage and increasing tube current settings.
AB  - PURPOSE: To prospectively assess the effects of lower tube voltage and various
      effective tube currents on image quality for computed tomographic (CT)
      angiography of the circle of Willis. MATERIALS AND METHODS: Institutional review
      board approval was obtained. Patients or family provided written informed
      consent. Signal-to-noise ratios (SNRs) were determined in a head phantom for
      various effective tube currents with tube voltages of 90, 120, and 140 kVp.
      Patients were referred for CT angiography because of acute subarachnoid
      hemorrhage (n = 20) or family history of cerebral aneurysms (n = 20). In each
      group, 10 patients were scanned with 120 kVp and 200 mAs(eff) and 10 were scanned
      with 90 kVp and 330 mAs(eff) (CT dose index volumes, 27.2 mGy and 20.6 mGy,
      respectively). CT numbers were measured in the internal carotid artery at the T
      junction and compared with a t test. Two radiologists used a five-point scale to
      subjectively score arterial enhancement, depiction of small arterial detail,
      image noise, venous contamination, and interference of subarachnoid blood. Mann
      Whitney U test was used for statistical analysis. RESULTS: In the phantom, SNR(2)
      was proportional to effective tube current and CT dose index volume. With an
      identical effective tube current, SNR(2) was lower at 90 kVp than at 120 or 140
      kVp. With identical CT dose index volume, tube voltage of 90 kVp resulted in a
      45%-52% increase of SNR(2) compared with SNR(2) at 120 kVp. In patients, mean
      attenuation in the internal carotid artery T junction was higher with 90 kVp (340
      HU) than with 120 kVp (252 HU, P < .001). Although dose at 90 kVp was 30% lower
      than dose at 120 kVp, scores for arterial enhancement and depiction of small
      arterial detail were higher at 90 kVp than at 120 kVp (4.0 vs 3.2 and 3.6 vs 3.1,
      respectively; P < .005). CONCLUSION: In head phantoms, lower tube voltage
      improved SNR at equal radiation doses. For CT angiography of the circle of
      Willis, this translated into superior image quality at 90 kVp.

PMID- 17229874
TI  - Choosing a radiology workstation: technical and clinical considerations.
AB  - Choosing a workstation for daily use in the interpretation of digital radiologic
      images can be a daunting task. There are numerous products available on the
      market, but differentiating among them and deciding on what is best for a
      particular environment can be confusing and frustrating. There is no "one-size
      fits-all" workstation, so users must consider a variety of factors when choosing
      a workstation. This review summarizes the critical elements in a radiology
      workstation and the characteristics one should be aware of and look for in the
      selection of a workstation. Issues pertaining to both hardware and software
      aspects of medical workstations, including interface design, are reviewed,
      particularly as they may affect the interpretation process.

PMID- 17229875
TI  - Clinical predictors of metastatic disease to the brain from non-small cell lung
      carcinoma: primary tumor size, cell type, and lymph node metastases.
AB  - PURPOSE: To retrospectively assess possible clinical predictors of metastatic
      disease to the brain in patients with non-small cell lung carcinoma (NSCLC).
      MATERIALS AND METHODS: Institutional review board approval was obtained, informed
      consent was waived, and data and other information were obtained prior to
      implementation of HIPAA. A review was performed of 264 patients (mean age, 65
      years; 158 men and 106 women) with NSCLC who had undergone imaging studies of the
      chest and head. Hierarchical logistic regression was used to determine the
      predicted probability of metastatic disease to the brain as a function of patient
      age and sex and of size, cell type, peripheral versus central location, and lymph
      node stage of the primary NSCLC. RESULTS: Ninety-five (36%) patients had evidence
      of metastatic disease to the brain. Mean diameter of the primary tumors was 4.0
      cm +/- 2.2 (standard deviation). Cell types included adenocarcinoma (136 [52%]
      patients), undifferentiated (68 [26%] patients), and squamous (47 [18%]
      patients), for which metastatic disease to the brain occurred in 43%, 41%, and
      13% (P = .003) of patients, respectively. The predicted probability of metastatic
      disease to the brain correlated positively with size of the primary tumor (P <
      .001), cell type (adenocarcinoma and undifferentiated vs squamous, P = .001), and
      lymph node stage (P < .017) but did not correlate with age, sex, or primary tumor
      location. For primary adenocarcinoma without lymph node spread, the predicted
      probabilities of metastatic disease to the brain from 2- and 6-cm primary tumors
      were .14 (95% confidence interval: .06, .27) and .72 (95% confidence interval:
      .48, .88), respectively (P < .02). CONCLUSION: The probability of metastatic
      disease to the brain from primary NSCLC is correlated with size of the primary
      tumor, cell type, and intrathoracic lymph node stage.

PMID- 17229876
TI  - Liver cancer: increased microwave delivery to ablation zone with cooled-shaft
      antenna--experimental and clinical studies.
AB  - PURPOSE: To prospectively investigate whether the ablation zone induced with
      microwaves could be increased by delivering greater energy with a cooled-shaft
      antenna. MATERIALS AND METHODS: All studies were animal care and ethics committee
      approved. Written informed consent was obtained from all patients. Microwave
      ablation was performed by using a cooled-shaft antenna in 48 ex vivo and 12 in
      vivo experiments with porcine livers. The coagulation diameters achieved in
      different microwave ablation parameter groups (60-90 W for 5-25 minutes) were
      compared. Ninety patients (78 men, 12 women; mean age, 53 years; age range, 20-82
      years) with 133 0.8-8.0-cm (mean, 2.7 cm +/- 1.5 [standard deviation]) primary or
      metastatic liver cancers were treated with the same microwave ablation technique.
      Complete ablation (CA) and local tumor progression (LTP) rates were determined.
      Generalized estimating equations were used to compare differences in tumor size,
      ablation zone diameter, and CA and LTP rates between different patient subgroups.
      RESULTS: In the ex vivo livers, in vivo livers, and liver cancers, one
      application of microwave energy with 80 W for 25 minutes produced mean
      coagulation diameters of 5.6 x 7.4 cm, 3.5 x 5.9 cm, and 3.6 x 5.0 cm,
      respectively. Skin burn was not observed. CA rates in small (<or=3.0-cm),
      intermediate (3.1-5.0-cm), and large (5.1-8.0-cm) liver cancers were 94% (81 of
      86), 91% (31 of 34), and 92% (12 of 13), respectively. During a mean follow-up
      period of 17.4 months, LTP occurred in seven (5%) treated cancers. There was a
      significant difference in LTP rate between the cirrhosis and no-cirrhosis groups
      (P = .03). Four patients had major complications. CONCLUSION: Delivery of greater
      microwave energy with cooled-shaft antennas yielded large ablation zones in ex
      vivo and in vivo livers and in liver cancers. Effective local tumor control was
      achieved during one microwave ablation session.

PMID- 17229877
TI  - Renal involvement in patients with autoimmune pancreatitis: CT and MR imaging
      findings.
AB  - PURPOSE: To retrospectively evaluate computed tomographic (CT) and magnetic
      resonance (MR) imaging renal findings at clinical presentation, during treatment,
      and at follow-up in patients with autoimmune pancreatitis (AIP). MATERIALS AND
      METHODS: This HIPAA-compliant study received institutional review board approval.
      All patients included had previously consented to the use of their medical
      records for the purpose of research. Forty-five patients (38 male and seven
      female patients; mean age, 64 years) with diagnosis of AIP were included. Forty
      patients underwent CT or MR imaging at clinical presentation; 33 patients
      (including five without imaging at presentation) underwent follow-up. CT and MR
      images were reviewed in consensus by two radiologists for the presence of renal
      involvement. Various features were evaluated. Clinical characteristics at
      presentation were compared between patients with and patients without renal
      involvement. RESULTS: Of the 40 patients who underwent imaging at presentation,
      14 (35%) had renal involvement (12 with parenchymal involvement and five with
      extraparenchymal involvement). Renal parenchymal lesions showed decreased
      enhancement and appeared as small peripheral cortical nodules, round or wedge
      shaped lesions, or diffuse patchy involvement. Thirteen patients with renal
      involvement at presentation underwent a follow-up study. Renal lesions in 10
      patients regressed (in nine, after steroid treatment) but progressed in three
      patients without steroid treatment. Renal lesions were found in two other
      patients during follow-up. No significant difference in the clinical
      characteristics was found between patients with and patients without renal
      involvement. CONCLUSION: Renal involvement in patients with AIP is relatively
      common and predominantly involves the cortex of the kidney. The lesions improve
      after steroid treatment but can progress without steroid treatment.

PMID- 17229878
TI  - Internal mammary arteries supplying hepatocellular carcinoma: vascular anatomy at
      digital subtraction angiography in 97 patients.
AB  - PURPOSE: To retrospectively evaluate the vascular anatomy of the internal mammary
      arteries that supply hepatocellular carcinomas (HCCs), with an emphasis on number
      of tumor feeders. MATERIALS AND METHODS: This retrospective study was approved by
      the institutional review board; informed consent was waived. Between August 1996
      and July 2005, internal mammary arteries that supply HCCs were found in 97 (2.2%)
      of 4438 patients (76 men, 21 women; mean age, 55 years +/- 10.5 [standard
      deviation]; range, 19-79 years). Computed tomographic scans and digital
      subtraction angiograms in these 97 patients were retrospectively reviewed in
      consensus by two interventional radiologists. Tumor size, number of tumor
      feeders, and tumor location were recorded. The t test and analysis of variance
      were used to correlate tumor size with number of tumor feeders, tumor feeder
      laterality, and transcatheter arterial chemoembolization (TACE) time. RESULTS:
      The following 125 tumor feeders were identified in 97 patients: phrenic branch (n
      = 59), musculophrenic artery (n = 40), superior epigastric artery (n = 15),
      anterior intercostal artery (n = 6), ensiform artery (n = 4), and
      pericardiacophrenic artery (n = 1). In two patients, tumors were in dorsal
      hepatic areas directly beneath the diaphragm. Half of the tumors located in liver
      segments II or III were supplied by the right internal mammary artery. In three
      patients, the tumor feeders from the left internal mammary artery crossed the
      midline. Tumor size was not statistically associated with number of tumor feeders
      (P = .076), tumor feeder laterality (P = .141), and TACE time (P = .729).
      CONCLUSION: The common tumor feeders of the internal mammary artery are the
      phrenic branch and the musculophrenic artery. Moreover, the internal mammary
      artery can supply a tumor even in the dorsal hepatic area.

PMID- 17229879
TI  - Carbon monoxide-mediated activation of large-conductance calcium-activated
      potassium channels contributes to mesenteric vasodilatation in cirrhotic rats.
AB  - Large-conductance calcium-activated potassium channels (BK(Ca)s) are important
      regulators of arterial tone and represent a mediator of the endogenous
      vasodilator carbon monoxide (CO). Because an up-regulation of the heme oxygenase
      (HO)/CO system has been associated with mesenteric vasodilatation of cirrhosis,
      we analyzed the interactions of BK(Ca) and of HO/CO in the endothelium-dependent
      dilatation of mesenteric arteries in ascitic cirrhotic rats. In pressurized
      mesenteric arteries (diameter, 170-350 microm) of ascitic cirrhotic rats, we
      evaluated the effect of inhibition of BK(Ca), HO, and guanylyl-cyclase on
      dilatation induced by acetylcholine and by exogenous CO; and HO-1 and BK(Ca)
      subunit protein expression. Inhibition of HO and of BK(Ca) reduced acetylcholine
      induced vasodilatation more in cirrhotic rats than in control rats, whereas
      inhibition of guanylyl-cyclase had a similar effect in the two groups. CO was
      more effective in cirrhotic rats than in control rats, and the effect was
      hindered by BK(Ca) inhibition. The expression of HO-1 and of BK(Ca) alpha-subunit
      was higher in mesenteric arteries of cirrhotic rats compared with that of control
      animals, whereas the expression of the BK(Ca) beta1-subunit was lower. In
      conclusion, an overexpression of BK(Ca) alpha-subunits, possibly due to HO up
      regulation with increased CO production, participates in the endothelium
      dependent alterations and mesenteric arterial vasodilatation of ascitic cirrhotic
      rats.

PMID- 17229880
TI  - Amyloid-beta in Alzheimer disease: the null versus the alternate hypotheses.
AB  - For nearly 20 years, the primary focus for researchers studying Alzheimer disease
      has been centered on amyloid-beta, such that the amyloid cascade hypothesis has
      become the "null hypothesis." Indeed, amyloid-beta is, by the current definition
      of the disease, an obligate player in pathophysiology, is toxic to neurons in
      vitro, and, perhaps most compelling, is increased by all of the human genetic
      influences on the disease. Therefore, targeting amyloid-beta is the focus of
      considerable basic and therapeutic interest. However, an increasingly vocal group
      of investigators are arriving at an "alternate hypothesis" stating that amyloid
      beta, while certainly involved in the disease, is not an initiating event but
      rather is secondary to other pathogenic events. Furthermore and perhaps most
      contrary to current thinking, the alternate hypothesis proposes that the role of
      amyloid-beta is not as a harbinger of death but rather a protective response to
      neuronal insult. To determine which hypothesis relates best to Alzheimer disease
      requires a broader view of disease pathogenesis and is discussed herein.

PMID- 17229881
TI  - Aberrant synaptic activation of N-methyl-D-aspartate receptors underlies ethanol
      withdrawal hyperexcitability.
AB  - Chronic ethanol exposure may induce neuroadaptive responses in N-methyl-d
      aspartate (NMDA) receptors, which are thought to underlie a variety of alcohol
      related brain disorders. Here, we demonstrate that hyperexcitability triggered by
      withdrawal from chronic ethanol exposure is associated with increases in both
      synaptic NMDA receptor expression and activation. Withdrawal from chronic ethanol
      exposure (75 mM ethanol, 5-9 days) elicited robust and prolonged epileptiform
      activity in CA1 pyramidal neurons from hippocampal explants, which was absolutely
      dependent upon NMDA receptor activation but independent of chronic inhibition of
      protein kinase A (PKA). Analysis of Sr(2+)-supported asynchronous NMDA receptor
      mediated miniature excitatory postsynaptic currents (mEPSCs) was employed to
      assess changes in NMDA neurotransmission. After chronic exposure, ethanol
      withdrawal was associated with an increase in mEPSC amplitude 3.38-fold over that
      after withdrawal from acute ethanol exposure. Analysis of paired evoked alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid EPSCs and spontaneous mEPSCs
      indicated that withdrawal after chronic exposure was also associated with a
      selective increase in action potential evoked but not spontaneous transmitter
      release probability. Immunoblot analysis revealed significant increases in total
      NR1, NR2A, and NR2B subunit expression after chronic exposure and unaffected by
      PKA-inhibition manner. Confocal imaging studies indicate that increased NR1
      subunit expression was associated with increased density of NR1 expression on
      dendrites in parallel with a selective increase in the size of NR1 puncta on
      dendritic spines. Therefore, neuroadaptation to chronic ethanol exposure in NMDA
      synaptic transmission is responsible for aberrant network excitability after
      withdrawal and results from changes in both postsynaptic function as well as
      presynaptic release.

PMID- 17229882
TI  - Recombinant protein-based assays for detection of antibodies to severe acute
      respiratory syndrome coronavirus spike and nucleocapsid proteins.
AB  - Recombinant severe acute respiratory syndrome (SARS) nucleocapsid and spike
      protein-based immunoglobulin G immunoassays were developed and evaluated. Our
      assays demonstrated high sensitivity and specificity to the SARS coronavirus in
      sera collected from patients as late as 2 years postonset of symptoms. These
      assays will be useful not only for routine SARS coronavirus diagnostics but also
      for epidemiological and antibody kinetic studies.

PMID- 17229883
TI  - Characterization of Plasmodium vivax heat shock protein 70 and evaluation of its
      value for serodiagnosis of tertian malaria.
AB  - We have characterized Plasmodium vivax heat shock protein 70 (PvHSP70) and
      evaluated serodiagnostic applicability of recombinant PvHSP70 (rPvHSP70). In
      enzyme-linked immunosorbent assays and immunoblot analyses, rPvHSP70 showed high
      sensitivity (88.8%; 203/228 cases). P. falciparum-infected sera revealed positive
      reactions (78.8%). The predominant immunoglobulin G (IgG) subclasses were
      segregated with IgG1 and IgG3.

PMID- 17229884
TI  - Evaluation of a novel enzyme-linked immunosorbent assay to detect immunoglobulin
      G antibody to enolase for serodiagnosis of invasive candidiasis.
AB  - The performance of a new test to detect antibodies to Candida albicans
      recombinant enolase was investigated in 47 immunocompromised and 51
      immunocompetent patients. The sensitivity, specificity, and positive and negative
      predictive values of the test for the diagnosis of invasive candidiasis were
      81.0, 83.9, 79.1, and 85.5%, respectively.

PMID- 17229885
TI  - Functional interaction of Aurora-A and PP2A during mitosis.
AB  - Entry into mitosis is a highly regulated process, promoted by the activated
      Cyclin B1/Cdk1 complex. Activation of this complex is controlled, in part, by the
      protein kinase Aurora-A, which is a member of a multigenic serine/threonine
      kinase family. In normal cells, Aurora-A activity is regulated, at least in part,
      by degradation through the APC-ubiquitin-proteasome pathway. It has recently been
      proposed that, in Xenopus, Aurora-A degradation can be inhibited by
      phosphorylation. It would thus be expected that a phosphatase activity would
      release this blockade at the end of mitosis. Here, we have shown that the protein
      phosphatase PP2A and Aurora-A are colocalized at the cell poles during mitosis in
      human cells and interact within the same complex. Using the PP2A inhibitor
      okadaic acid and an RNAi approach, we have shown that this interaction is
      functional within the cell. PP2A/Aurora-A interaction is promoted by an S51D
      mutation in Aurora-A and inhibited by a phosphomimetic peptide centered around
      Aurora-A S51, thereby strongly suggesting that PP2A controls Aurora-A degradation
      by dephosphorylating serine 51 in the A box of the human enzyme.

PMID- 17229887
TI  - NHERF links the N-cadherin/catenin complex to the platelet-derived growth factor
      receptor to modulate the actin cytoskeleton and regulate cell motility.
AB  - Using phage display, we identified Na+/H+ exchanger regulatory factor (NHERF)-2
      as a novel binding partner for the cadherin-associated protein, beta-catenin. We
      showed that the second of two PSD-95/Dlg/ZO-1 (PDZ) domains of NHERF interacts
      with a PDZ-binding motif at the very carboxy terminus of beta-catenin. N-cadherin
      expression has been shown to induce motility in a number of cell types. The first
      PDZ domain of NHERF is known to bind platelet-derived growth factor-receptor beta
      (PDGF-Rbeta), and the interaction of PDGF-Rbeta with NHERF leads to enhanced cell
      spreading and motility. Here we show that beta-catenin and N-cadherin are in a
      complex with NHERF and PDGF-Rbeta at membrane ruffles in the highly invasive
      fibrosarcoma cell line HT1080. Using a stable short hairpin RNA system, we showed
      that HT1080 cells knocked down for either N-cadherin or NHERF had impaired
      ability to migrate into the wounded area in a scratch assay, similar to cells
      treated with a PDGF-R kinase inhibitor. Cells expressing a mutant NHERF that is
      unable to associate with beta-catenin had increased stress fibers, reduced
      lamellipodia, and impaired cell migration. Using HeLa cells, which express little
      to no PDGF-R, we introduced PDGF-Rbeta and showed that it coimmunoprecipitates
      with N-cadherin and that PDGF-dependent cell migration was reduced in these cells
      when we knocked-down expression of N-cadherin or NHERF. These studies implicate N
      cadherin and beta-catenin in cell migration via PDGF-R-mediated signaling through
      the scaffolding molecule NHERF.

PMID- 17229886
TI  - Avl9p, a member of a novel protein superfamily, functions in the late secretory
      pathway.
AB  - The branching of exocytic transport routes in both yeast and mammalian cells has
      complicated studies of the late secretory pathway, and the mechanisms involved in
      exocytic cargo sorting and exit from the Golgi and endosomes are not well
      understood. Because cargo can be sorted away from a blocked route and secreted by
      an alternate route, mutants defective in only one route do not exhibit a strong
      secretory phenotype and are therefore difficult to isolate. In a genetic screen
      designed to isolate such mutants, we identified a novel conserved protein, Avl9p,
      the absence of which conferred lethality in a vps1Delta apl2Delta strain
      background (lacking a dynamin and an adaptor-protein complex 1 subunit).
      Depletion of Avl9p in this strain resulted in secretory defects as well as
      accumulation of Golgi-like membranes. The triple mutant also had a depolarized
      actin cytoskeleton and defects in polarized secretion. Overexpression of Avl9p in
      wild-type cells resulted in vesicle accumulation and a post-Golgi defect in
      secretion. Phylogenetic analysis indicated evolutionary relationships between
      Avl9p and regulators of membrane traffic and actin function.

PMID- 17229888
TI  - Genetic control of fusion pore expansion in the epidermis of Caenorhabditis
      elegans.
AB  - Developmental cell fusion is found in germlines, muscles, bones, placentae, and
      stem cells. In Caenorhabditis elegans 300 somatic cells fuse during development.
      Although there is extensive information on the early intermediates of viral
      induced and intracellular membrane fusion, little is known about late stages in
      membrane fusion. To dissect the pathway of cell fusion in C. elegans embryos, we
      use genetic and kinetic analyses using live-confocal and electron microscopy. We
      simultaneously monitor the rates of multiple cell fusions in developing embryos
      and find kinetically distinct stages of initiation and completion of membrane
      fusion in the epidermis. The stages of cell fusion are differentially blocked or
      retarded in eff-1 and idf-1 mutants. We generate kinetic cell fusion maps for
      embryos grown at different temperatures. Different sides of the same cell differ
      in their fusogenicity: the left and right membrane domains are fusion
      incompetent, whereas the anterior and posterior membrane domains fuse with
      autonomous kinetics in embryos. All but one cell pair can initiate the formation
      of the largest syncytium. The first cell fusion does not trigger a wave of
      orderly fusions in either direction. Ultrastructural studies show that epidermal
      syncytiogenesis require eff-1 activities to initiate and expand membrane merger.

PMID- 17229889
TI  - Spongiform neurodegeneration-associated E3 ligase Mahogunin ubiquitylates TSG101
      and regulates endosomal trafficking.
AB  - A null mutation in the gene encoding the putative E3 ubiquitin-protein ligase
      Mahogunin causes spongiform neurodegeneration, a recessively transmitted prion
      like disease in mice. However, no substrates of Mahogunin have been identified,
      and the cellular role of Mahogunin is unknown. Here, we report the identification
      of TSG101, a key component of the endosomal sorting complex required for
      transport (ESCRT)-I, as a specific Mahogunin substrate. We find that Mahogunin
      interacts with the ubiquitin E2 variant (UEV) domain of TSG101 via its PSAP motif
      and that it catalyzes monoubiquitylation of TSG101 both in vivo and in vitro.
      Depletion of Mahogunin by small interfering RNAs in mammalian cells disrupts
      endosome-to-lysosome trafficking of epidermal growth factor receptor, resulting
      in prolonged activation of a downstream signaling cascade. Our findings support a
      role for Mahogunin in a proteasome-independent ubiquitylation pathway and suggest
      a link between dysregulation of endosomal trafficking and spongiform
      neurodegeneration.

PMID- 17229890
TI  - Cornichon-like protein facilitates secretion of HB-EGF and regulates proper
      development of cranial nerves.
AB  - During their migration to the periphery, cranial neural crest cells (NCCs) are
      repulsed by an ErbB4-dependent cue(s) in the mesenchyme adjoining rhombomeres (r)
      3 and 5, which are segmented hindbrain neuromeres. ErbB4 has many ligands, but
      which ligand functions in the above system has not yet been clearly determined.
      Here we found that a cornichon-like protein/cornichon homolog 2 (CNIL/CNIH2) gene
      was expressed in the developing chick r3 and r5. In a cell culture system, its
      product facilitated the secretion of heparin-binding epidermal growth factor-like
      growth factor (HB-EGF), one of the ligands of ErbB4. When CNIL function was
      perturbed in chick embryos by forced expression of a truncated form of CNIL, the
      distribution of NCCs was affected, which resulted in abnormal nerve fiber
      connections among the cranial sensory ganglia. Also, knockdown of CNIL or HB-EGF
      with siRNAs yielded a similar phenotype. This phenotype closely resembled that of
      ErbB4 knockout mouse embryos. Because HB-EGF was uniformly expressed in the
      embryonic hindbrain, CNIL seems to confine the site of HB-EGF action to r3 and r5
      in concert with ErbB4.

PMID- 17229891
TI  - DYRK1A autophosphorylation on serine residue 520 modulates its kinase activity
      via 14-3-3 binding.
AB  - Dual-specificity tyrosine-phosphorylated and regulated kinase (DYRK) proteins are
      an evolutionarily conserved family of protein kinases, with members identified
      from yeast to humans, that participate in a variety of cellular processes. DYRKs
      are serine/threonine protein kinases that are activated by autophosphorylation on
      a tyrosine residue in the activation loop. The family member DYRK1A has been
      shown to phosphorylate several cytosolic proteins and a number of splicing and
      transcription factors, including members of the nuclear factor of activated T
      cells family. In the present study, we show that DYRK1A autophosphorylates, via
      an intramolecular mechanism, on Ser-520, in the PEST domain of the protein. We
      also show that phosphorylation of this residue, which we show is subjected to
      dynamic changes in vivo, mediates the interaction of DYRK1A with 14-3-3beta. A
      second 14-3-3 binding site is present within the N-terminal of the protein. In
      the context of the DYRK1A molecule, neither site can act independently of the
      other. Bacterially produced DYRK1A and the mutant DYRK1A/S520A have similar
      kinase activities, suggesting that Ser-520 phosphorylation does not affect the
      intrinsic kinase activity on its own. Instead, we demonstrate that this
      phosphorylation allows the binding of 14-3-3beta, which in turn stimulates the
      catalytic activity of DYRK1A. These findings provide evidence for a novel
      mechanism for the regulation of DYRK1A kinase activity.

PMID- 17229894
TI  - The triglyceride-lowering effects of a modest dose of docosahexaenoic acid alone
      versus in combination with low dose eicosapentaenoic acid in patients with
      coronary artery disease and elevated triglycerides.
AB  - BACKGROUND: Hypertriglyceridemia is a risk factor for coronary artery disease
      (CAD). The American Heart Association recommends 1000 mg of omega-3 fatty acids,
      docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), daily for
      cardioprotection and higher doses for triglyceride-lowering in patients with CAD.
      METHODS: This was a prospective, randomized, double-blind study comparing DHA to
      DHA + EPA in patients with CAD and triglycerides greater than 200 mg/dL. Subjects
      were randomized to either 1000 mg of DHA or 1252 mg of DHA + EPA for eight weeks.
      Baseline and eight-week laboratories were drawn to assess changes in the fasting
      lipid profile. The primary objective was to evaluate the change in triglycerides
      between the two groups at eight weeks. RESULTS: A total of 116 subjects were
      enrolled; 57 in the DHA group and 59 in the DHA + EPA group. Baseline
      characteristics were similar between groups. The mean age was 69.4 +/- 9.1 years
      and 70.7% were male. Triglycerides decreased by an average of 21.8% in the DHA
      group (p < 0.001) and 18.3% in the DHA + EPA group (p < 0.001). The difference
      between groups was not significant. A greater proportion of subjects in the DHA
      group achieved triglyceride goal (less than 150 mg/dL) compared to the DHA + EPA
      group (24.6% versus 10.2%, p < 0.05). CONCLUSIONS: Our results indicate that the
      American Heart Association recommended cardioprotective dose of omega-3 fatty
      acids can also significantly lower triglycerides in patients with CAD. There do
      not appear to be significant differences in triglyceride-lowering between DHA
      only and DHA + EPA combination products when dosing is based on DHA.

PMID- 17229893
TI  - Tea consumption and infarct-related ventricular arrhythmias: the determinants of
      myocardial infarction onset study.
AB  - BACKGROUND: Tea consumption is associated with lower post-infarct mortality among
      patients with acute myocardial infarction. We previously found preliminary
      evidence that tea consumption may also be associated with lower risk of infarct
      related ventricular arrhythmias. METHODS: Between 1989 and 1996, 3882 subjects
      with AMI were enrolled in the two phases of the Determinants of Myocardial
      Infarction Onset Study a median of four days after admission. Trained
      interviewers assessed self-reported usual tea and coffee consumption during the
      year prior to infarction with a standardized questionnaire. We examined the
      prevalence of ventricular arrhythmias in the two phases of the study separately
      and together. RESULTS: Among the 1912 patients with complete information in the
      first phase, the prevalence of ventricular arrhythmias was 16% among abstainers
      from tea, 11% among moderate tea drinkers (<14 cups per week), and 14% among
      heavier tea drinkers (> or =14 cups per week) (p homogeneity = 0.03). Among the
      1791 patients with comparable information in the second phase, the corresponding
      prevalence rates were 11%, 8%, and 8%, respectively (p = 0.06). When the phases
      were combined, the adjusted odds ratios for VA were 0.7 (95% confidence interval,
      0.6-0.9) among moderate tea drinkers and 0.9 (95% confidence interval, 0.7-1.2)
      among heavier tea drinkers. The findings were of similar direction for both
      ventricular tachycardia and fibrillation. In contrast, there was higher risk of
      VA with increasing coffee intake (odds ratio for >14 cups per week 1.3; 95%
      confidence interval, 1.0-1.7; p trend 0.02). CONCLUSIONS: Moderate tea intake is
      associated with a lower prevalence, and higher coffee intake with a slightly
      higher prevalence, of ventricular arrhythmias among patients hospitalized with
      acute myocardial infarction. If the association with tea intake is confirmed, it
      may suggest new approaches to prevention of ischemia-related arrhythmias.

PMID- 17229895
TI  - Magnesium intake is related to improved insulin homeostasis in the framingham
      offspring cohort.
AB  - OBJECTIVE: Higher dietary intake of magnesium may protect against development of
      type 2 diabetes. The aim of this study was to examine the association between
      dietary magnesium intake and metabolic risk factors for diabetes. METHODS: We
      examined cross-sectional associations between magnesium intake and fasting
      glucose and insulin, 2-hour post-challenge plasma glucose and insulin, and
      insulin resistance assessed by the homeostasis model (HOMA-IR) in 1223 men and
      1485 women without diabetes from the Framingham Offspring cohort. Magnesium
      intake was assessed by a food frequency questionnaire and magnesium intake was
      categorized into quintile categories. Geometric mean insulin, glucose, 2-hour
      post challenge plasma glucose and insulin concentrations and HOMA-IR were
      estimated across quintile categories of magnesium intake using Generalized Linear
      Models. RESULTS: After adjustment for potential confounding factors, magnesium
      intake was inversely associated with fasting insulin (mean: 29.9 vs 26.7
      microU/mL in the lowest vs highest quintiles of magnesium intake; P trend
      <0.001), post-glucose challenge plasma insulin (86.4 vs 72 microU/mL; P trend
      <0.001), and HOMA-IR (7.0 vs 6.2; P trend <0.001). No significant association was
      found between magnesium intake and fasting glucose or 2-hour post challenge
      glucose. CONCLUSIONS: Improved insulin sensitivity may be one mechanism by which
      higher dietary magnesium intake may reduce the risk of developing type 2 DM.

PMID- 17229896
TI  - Eight-year longitudinal changes in body composition in healthy Swiss adults.
AB  - OBJECTIVE: Significant changes in body composition occur during lifetime. This
      longitudinal study (8.0 +/- 0.8 yrs) in a cohort of healthy sedentary and
      physically active men (n = 78) and women (n = 53), aged 20 to 74 yr describes: 1)
      the longitudinal changes in weight and body composition and 2) their associations
      with age and physical activity. METHOD: Fat-free mass (FFM) and body fat (BF)
      were assessed by bioelectrical impedance analysis (BIA). Subjects who regularly
      performed >3 hours per week of endurance type physical activity were classified
      as "Active". Others were classified as "Sedentary". Subjects were also separated
      by age (<45 yr vs > or =45 yr). RESULTS: FFM increased by 1.7 +/- 2.8 kg in men
      <45 yr who gained 4.0 +/- 5.0 kg of body weight and was maintained (0.5 +/- 1.6
      kg) in women <45 y who gained 1.6 +/- 3.0 kg of weight. A weight gain of 1.2 +/-
      3.3 kg in men > or =45 yr was accompanied by stable FFM (-0.1 +/- 2.3 kg), and of
      1.0 +/- 3.2 kg was accompanied by a loss of FFM in women > or =45 yr. In active
      men > or =45 yr, maintenance of FFM was associated with smaller weight gains than
      in sedentary; sedentary men > or =45 yr decreased FFM with larger weight gains
      than active subjects. Sedentary women <45 yr were able to gain FFM; the active
      women maintained, but did not gain FFM with smaller weight gains than in
      sedentary women. FFM decreased in >/=45 yr women despite of small weight gains.
      CONCLUSION: Weight change is clearly associated with a change in FFM. Weight gain
      is necessary to offset age-related FFM loss between 20 and 74 yrs. In active men,
      a FFM increase was associated with less weight gain than sedentary men. Future
      studies should evaluate the threshold of weight change and the level of physical
      activity necessary to prevent age-related losses of FFM.

PMID- 17229897
TI  - Low folate and the risk of cognitive and functional deficits in the very old: the
      Monzino 80-plus study.
AB  - OBJECTIVE: To cross sectionally investigate the association of serum vitamin
      B(12) and folate concentrations with cognitive and functional ability in the very
      old in the general population. METHODS: Serum vitamin B(12) and folate
      concentrations were assessed in 471 consenting subjects participating in the
      Monzino 80-plus study (mean age: 87.4 years), a door-to-door population-based
      survey among very old subjects living in Northern Italy. Cognitive and functional
      evaluations included Mini-Mental State Examination (MMSE), Instrumental
      Activities of Daily Living (IADL) and Spontaneous Behavior Interview-basic
      Activities of Daily Living (SBI-bADL). RESULTS: MMSE, IADL and SBI-bADL scores
      were all significantly correlated with folate concentrations (respectively: r =
      0.36, r = -0.39, r = -0.35; p < 0.0001), while no significant associations were
      found with vitamin B(12) concentrations. When entered into multiple linear
      regression analyses with several covariates, folate showed a highly significant,
      curvilinear association with both cognitive and functional scores (p < 0.0001).
      Subjects in low and middle folate tertiles had significantly higher odds ratios
      for dementia (p < 0.0001; adjusted ORs = 5.40 and 6.56, lower 95% CIs 2.53 and
      3.11, higher 95% CIs 12.73 and 15.29). CONCLUSIONS: Findings of this population
      based study suggest that subclinical folate deficiency may represent a risk
      factor for the cognitive decline associated with aging that could contribute to
      AD as well as other dementia development.

PMID- 17229898
TI  - Serum magnesium and type-2 diabetes in African Americans and Hispanics: a New
      York cohort.
AB  - OBJECTIVES: The aim of this study was to examine the relationship of serum Mg
      with stage of diabetes measured by fasting serum glucose in a cohort of 485
      African American and Hispanic adults. METHODS: The cross sectional Rosetta study
      was designed to assess body composition in a multi-racial cohort of healthy
      adults living in New York City. The data utilized for the current analyses were
      collected during the years 1990 to 2000. Serum Mg and glucose were measured after
      a 10-12 hour fast. Dual-energy x-ray absorptiometry was used to measure fat mass
      (FM) and fat free mass (FFM). RESULTS: The mean age of the cohort was 53 +/- 16
      years. Hispanics had significantly lower (p < 0.05) mean serum Mg levels (0.82 +/
      0.07 mmol/L vs. 0.85 +/- 0.07 mmol/L) and FFM (48.8 +/- 10.9 kg vs. 50.9 +/-
      10.3 kg) compared to African Americans. In both race/ethnic groups, individuals
      classified as having diabetes had significantly (p < 0.001) lower serum
      concentrations of Mg (0.80 +/- 0.07 mmol/L) compared to the normal group (0.84 +/
      0.07 mmol/L). CONCLUSIONS: These results show that in African American and
      Hispanic adults, those with diabetes have lower serum Mg levels compared to those
      classified as pre-diabetic or those with normal fasting glucose levels.

PMID- 17229899
TI  - Treating irritable bowel syndrome with a food elimination diet followed by food
      challenge and probiotics.
AB  - OBJECTIVE: In Irritable Bowel Syndrome, the gut-associated immune system may be
      up-regulated resulting in immune complex production, low-grade inflammation, loss
      of Class I bacteria, and translocation of inflammatory mediators and
      macromolecules outside of the GI lumen. Since food intolerance may be one of the
      reasons for this upregulation, our goal was to investigate the role of food
      intolerance in IBS patients. METHODS: In this open label pilot study, we enrolled
      20 patients with IBS by Rome II criteria (15 women, ages 24-81) who had failed
      standard medical therapies in a tertiary care GI clinic. Baseline serum IgE and
      IgG food and mold panels, and comprehensive stool analysis (CSA) were performed.
      Breath-hydrogen testing and IBS Quality-of-Life (QOL) questionnaires were
      obtained. Patients underwent food elimination diets based on the results of food
      and mold panels followed by controlled food challenge. Probiotics were also
      introduced. Repeat testing was performed at 6-months. We followed up with this
      cohort at 1 year after trial completion to assess the reported intervention and
      for placebo effect. RESULTS: Baseline abnormalities were identified on serum IgG
      food and mold panels in 100% of the study subjects with significant improvement
      after food elimination and rotation diet (p < 0.05). Significant improvements
      were seen in stool frequency (p < 0.05), pain (p < 0.05), and IBS-QOL scores (p <
      0.0001). Imbalances of beneficial flora and dysbiotic flora were identified in
      100% of subjects by CSA. There was a trend to improvement of beneficial flora
      after treatment but no change in dysbiotic flora. The 1-year follow up
      demonstrated significant continued adherence to the food rotation diet (4.00 +/-
      1.45), minimal symptomatic problems with IBS (4.00 +/- 1.17), and perception of
      control over IBS (4.15 +/- 1.23). The continued use of probiotics was considered
      less helpful (3.40 +/- 1.60). CONCLUSION: These data demonstrate that identifying
      and appropriately addressing food sensitivity in IBS patients not previously
      responding to standard therapy results in a sustained clinical response and
      impacts on overall well being and quality of life in this challenging entity.

PMID- 17229900
TI  - Association of calcium intake, dairy product consumption with overweight status
      in young adults (1995-1996): the Bogalusa Heart Study.
AB  - OBJECTIVE: To examine the association between calcium intake and dairy product
      consumption with overweight and obesity in young adults. METHODS: The sample used
      in this study consisted of 1306 young adults, ages 19-38 years, who participated
      in the 1995-1996 young adult survey. Analysis was performed with analysis of
      covariance (ANCOVA) for ethnicity-gender groups separately. RESULTS: No
      significant association was found between dairy product consumption, calcium
      intake and overweight, defined by body mass index or waist circumference.
      However, there was a significant inverse association between calcium intake, low
      fat dairy product consumption and waist-to-hip ratio in white males. CONCLUSION:
      Increasing intake of calcium and low-fat dairy products may be associated with
      lower abdominal adiposity, particularly in young adult white males.

PMID- 17229901
TI  - Randomised, controlled, cross-over trial of soy protein with isoflavones on blood
      pressure and arterial function in hypertensive subjects.
AB  - OBJECTIVE: To examine the effects of dietary soy/isoflavones on 24 hr blood
      pressure profiles and arterial function [systemic arterial compliance (SAC),
      pulse wave velocity (PWV) and brachial arterial flow mediated vasodilation (FMD)]
      compared to non legume-based plant protein without isoflavones, in hypertensive
      subjects. DESIGN: In a 6 month double-blind, placebo controlled, cross-over
      trial, 41 hypertensive subjects (26 men, 15 postmenopausal women), 30-75 years,
      received soy cereal (40 g soy protein, 118 mg isoflavones) and gluten placebo
      cereal, each for 3 months. RESULTS: Thirty-eight subjects completed protocol with
      results expressed as mean or mean change (+/-SEM) with each intervention. Soy
      increased urinary isoflavones (daidzein: 8-fold; genistein: 8-fold; equol: 9
      fold; ODMA: 18-fold) with no change during gluten placebo. There was no
      difference in the change in individual 24 hr ambulatory BP parameters (SBP: 2 +/-
      2 vs -1 +/- 1 mmHg, p = 0.21; DBP: 1 +/- 1 vs -1 +/- 1 mmHg, p = 0.06) central BP
      (cSBP: -4 +/- 2 vs 0 +/- 2 mmHg, p = 0.2) or the change in arterial function
      (FMD: 0.3 +/- 0.5 vs -0.2 +/- 0.5%, p = NS; SAC: 0.02 +/- 0.02 vs -0.02 +/- 0.02
      U/mmHg, p = NS; PWV central: -0.2 +/- 0.2 vs 0.0 +/- 0.2 m/sec, p = NS; PWV
      peripheral: 0.01 +/- 0.3 vs -0.4 +/- 0.4 m/sec, p = NS) noted between
      interventions. Analysis of the area under curve of 24 hr BP outputs demonstrated
      that soy protein compared to gluten protein resulted in higher 24 hr systolic BP
      by 2.3 mmHg (p = 0.003), a higher daytime systolic BP by 3.4 mmHg (p = 0.0002)
      and a higher daytime diastolic BP by 1.4 mmHg (p = 0.008). Overall 24 hr
      diastolic BP, night systolic BP and night diastolic BP were not significantly
      different between groups. Furthermore, soy protein compared to gluten protein
      resulted in higher 24 hr heart rates by 3.5 bpm (p < 0.0001). CONCLUSIONS: In
      hypertensive subjects, compared to gluten placebo, soy dietary supplementation
      containing isoflavones had no effect on arterial function, on average 24 hr
      ambulatory blood pressure parameters or central blood pressure in men and women
      with hypertension. Area under the curve of 24 hr profiles demonstrated that
      daytime BP was higher after soy compared to gluten.

PMID- 17229902
TI  - Influence of long-term administration of lactulose and Saccharomyces boulardii on
      the colonic generation of phenolic compounds in healthy human subjects.
AB  - OBJECTIVE: Proteins are degraded in the colon by bacterial fermentation into
      potentially toxic metabolites such as phenolic compounds. The aim of the present
      study was to investigate whether long-term administration of lactulose or
      Saccharomyces boulardii cells would result in a lower protein degradation. In
      addition, the influence of a long-term dietary intake on different
      gastrointestinal parameters was investigated. METHODS: The effect of long-term
      intervention of the substrates was evaluated in a randomized, cross-over study in
      43 healthy volunteers. At the start of the study and at the end of each 4-week
      treatment period, urine was collected during 48 h in different fractions and
      faeces during 72 h. Breath test samples and blood samples were taken to study
      gastrointestinal parameters. RESULTS: No influence of long-term administration of
      both substrates was found on GE, OCTT and serum lipids. A significant decrease in
      small intestinal permeability was found after long-term dietary intervention with
      lactulose. Long-term administration of lactulose significantly decreased urinary
      p-cresol excretion, but did not lower fecal p-cresol excretion. No significant
      effects were observed after S. boulardii intake. CONCLUSION: The results obtained
      in present study have indicated that colonic amino acid fermentation can be
      reduced by the administration of lactulose as a fermentable carbohydrate.

PMID- 17229904
TI  - Efficient generation of CD34+ progenitor-derived dendritic cells from G-CSF
      mobilized peripheral mononuclear cells does not require hematopoietic stem cell
      enrichment.
AB  - As a result of their potent antigen-presentation function, dendritic cells (DC)
      are important tools for cell therapy programs. In vitro-generated DC from
      enriched CD34+ hematopoietic stem cells (HSC; enriched CD34 DC) have already
      proven their efficiency in Phase I/II clinical trials. Here, we investigated
      whether enrichment of CD34+ HSC before the onset of culture was absolutely
      required for their differentiation into DC. With this aim, we developed a new two
      step culture method. PBMC harvested from G-CSF-mobilized, healthy patients were
      expanded for 7 days during the first step, with early acting cytokines, such as
      stem cell factor, fetal liver tyrosine kinase 3 ligand (Flt-3L), and
      thrombopoietin. During the second step, expanded cells were then induced to
      differentiate into mature DC in the presence of GM-CSF, Flt-3L, and TNF-alpha for
      8 days, followed by LPS exposure for 2 additional days. Our results showed that
      the rate of CD34+/CD38+/lineageneg cells increased 19.5+/-10-fold (mean+/-sd)
      during the first step, and the expression of CD14, CD1a, CD86, CD80, and CD83
      molecules was up-regulated markedly following the second step. When compared with
      DC generated from enriched CD34+ cells, which were expanded for 7 days before
      differentiation, DC derived from nonenriched peripheral blood stem cells showed a
      similar phenotye but higher yields of production. Accordingly, the allogeneic
      stimulatory capacity of the two-step-cultured DC was as at least as efficient as
      that of enriched CD34 DC. In conclusion, we report herein a new two-step culture
      method that leads to high yields of mature DC without any need of CD34+ HSC
      enrichment.

PMID- 17229905
TI  - Renal iron metabolism: transferrin iron delivery and the role of iron regulatory
      proteins.

PMID- 17229906
TI  - Physiology and pathophysiology of heme: implications for kidney disease.
AB  - An iron-containing, tetrapyrrole ring, heme is an essential prosthetic group in
      an array of proteins that comprehensively affect cellular function and
      metabolism; yet "free" heme in sufficient amounts can be damaging to the kidney
      and other organs because of its bioreactivity and pro-oxidant effects. This
      review discusses the cellular metabolism of heme in health and disease and covers
      such areas as the synthesis of heme and its utilization in heme proteins;
      mechanisms underlying the toxicity of heme; and the extent to which
      pathophysiologic processes, such as renal incorporation of heme proteins or
      destabilization of intracellular heme proteins, increase intracellular levels of
      heme and provoke renal injury. The main catabolic process that degrades heme, the
      heme oxygenase (HO) system, is reviewed, and evidence for the protective effects
      of HO-1 against acute and chronic heme/heme protein-induced renal injury is
      summarized. Finally, current views regarding the molecular basis for heme-induced
      upregulation of HO-1 are discussed.

PMID- 17229907
TI  - Dual action of neutrophil gelatinase-associated lipocalin.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL) is expressed and secreted by
      immune cells, hepatocytes, and renal tubular cells in various pathologic states.
      NGAL exerts bacteriostatic effects, which are explained by its ability to capture
      and deplete siderophores, small iron-binding molecules that are synthesized by
      certain bacteria as a means of iron acquisition. Consistently, NGAL deficiency in
      genetically modified mice leads to an increased growth of bacteria. However,
      growing evidence suggests effects of the protein beyond fighting microorganisms.
      NGAL acts as a growth and differentiation factor in multiple cell types,
      including developing and mature renal epithelia, and some of this activity is
      enhanced in the presence of siderophore:iron complexes. This has led to the
      hypothesis that eukaryotes might synthesize siderophore-like molecules that bind
      NGAL. Accordingly, NGAL-mediated iron shuttling between the extracellular and
      intracellular spaces may explain some of the biologic activities of the protein.
      Interest in NGAL has been sparked by the observation that NGAL is massively
      upregulated after renal tubular injury and may participate in limiting kidney
      damage. This review summarizes the current knowledge about the dual effects of
      NGAL as a siderophore:iron-binding protein and as a growth factor and examines
      the role of these effects in renal injury.

PMID- 17229908
TI  - Clinical aspects of iron use in the anemia of kidney disease.

PMID- 17229909
TI  - Efficient removal of immunoglobulin free light chains by hemodialysis for
      multiple myeloma: in vitro and in vivo studies.
AB  - Of patients with newly diagnosed multiple myeloma, approximately 10% have
      dialysis-dependent acute renal failure, with cast nephropathy, caused by
      monoclonal free light chains (FLC). Of these, 80 to 90% require long-term renal
      replacement therapy. Early treatment by plasma exchange reduces serum FLC
      concentrations, but randomized, controlled trials have shown no evidence of renal
      recovery. This outcome can be explained by the low efficiency of the procedure. A
      model of FLC production, distribution, and metabolism in patients with myeloma
      indicated that plasma exchange might remove only 25% of the total amount during a
      3-wk period. For increasing FLC removal, extended hemodialysis with a protein
      leaking dialyzer was used. In vitro studies indicated that the Gambro HCO 1100
      dialyzer was the most efficient of seven tested. Model calculations suggested
      that it might remove 90% of FLC during 3 wk. This dialyzer then was evaluated in
      eight patients with myeloma and renal failure. Serum FLC reduced by 35 to 70%
      within 2 hr, but reduction rates slowed as extravascular re-equilibration
      occurred. FLC concentrations rebounded on successive days unless chemotherapy was
      effective. Five additional patients with acute renal failure that was caused by
      cast nephropathy then were treated aggressively, and three became dialysis
      independent. A total of 1.7 kg of FLC was removed from one patient during 6 wk.
      Extended hemodialysis with the Gambro HCO 1100 dialyzer allowed continuous, safe
      removal of FLC in large amounts. Proof of clinical value now will require larger
      studies.

PMID- 17229910
TI  - Molecular control of iron transport.
AB  - The iron-regulatory hormone hepcidin is a 25-amino acid peptide that is
      synthesized in hepatocytes. Hepcidin binds to the cellular iron export channel
      ferroportin and causes its internalization and degradation and thereby decreases
      iron efflux from iron exporting tissues into plasma. By this mechanism, hepcidin
      inhibits dietary iron absorption, the efflux of recycled iron from splenic and
      hepatic macrophages, and the release of iron from storage in hepatocytes.
      Hepcidin synthesis is stimulated by plasma iron and iron stores and is inhibited
      by erythropoietic activity, ensuring that extracellular plasma iron
      concentrations and iron stores remain stable and the erythropoietic demand for
      iron is met. During inflammation, increased hepcidin concentrations cause iron
      sequestration in macrophages, resulting in hypoferremia and eventually anemia of
      inflammation. Hepcidin deficiency plays a central role in most iron overload
      disorders. The role of hepcidin abnormalities in anemias that are associated with
      renal disease and in resistance to erythropoietic therapies remains to be
      elucidated.

PMID- 17229911
TI  - Center effects in anemia management of dialysis patients.
AB  - This study set out to determine whether there is a center effect on anemia
      management in hemodialysis patients. The US Renal Data System and Medicare
      standard analysis files were analyzed. Between-center variation and within
      facility correlations in hematocrit values were examined in two separate data
      sets (years 2000 and 2001) and compared with simulated samples that were composed
      of random values that assumed no center effect. Mixed-effect models were used to
      adjust for multiple factors and quantify the within-facility correlation in
      hematocrit values. Expected hematocrit values were compared in patients who
      underwent dialysis at poor and superior performing facilities with fixed
      characteristics including epoetin alpha dosing. There was a wider center
      variation in hematocrit for the actual versus simulated data and a coefficient of
      variation of 4.1% for the former versus 1.7% for the latter, in both years. The
      within-facility correlation for hematocrit was 0.053 (95% confidence interval
      0.050 to 0.056; P < 0.001) in 2000 with similar values in 2001 but no within
      facility correlation in the simulated data. The impact of these findings was
      demonstrated with a difference in expected hematocrit for a patient who was
      treated with fixed-dosage epoetin alpha in the poorest versus best performing
      units (mean difference in expected hematocrit 3.06; 95% confidence interval 3.03
      to 3.09; P < 0.001). Key attributes of a center effect on anemia management in
      hemodialysis have been identified. The presence of a center effect suggests that
      there are facility-specific processes that influence performance in dialysis
      anemia management and are independent of commonly titrated inputs, such as dosing
      of erythropoietic agents.

PMID- 17229912
TI  - Human renal organic anion transporter 4 operates as an asymmetric urate
      transporter.
AB  - Human organic anion transporter 4 (hOAT4) is located at the apical membrane of
      proximal tubule cells and involved in renal secretion and reabsorption of
      endogenous substances as well as many drugs and xenobiotics. This study
      reevaluated the physiologic role, transport mode, and driving forces of hOAT4. 6
      Carboxyfluorescein (6-CF) uptake into HEK293 cells that stably expressed hOAT4
      was saturable, resulting in a K(m) of 108 muM. 6-CF as well as [(3)H]estrone
      sulfate ([(3)H]ES) accumulation by HEK293-hOAT4 cells were abolished by ES,
      dehydroepiandrosterone sulfate, sulfinpyrazone, benzbromarone, and probenecid,
      whereas several OA, including p-aminohippurate (PAH), lactate, pyrazinoate,
      nicotinate, glutarate, and the diuretic hydrochlorothiazide (HCTZ) exhibited a
      slight or a NS inhibitory effect. PAH and glutarate are not taken up by HEK293
      hOAT4 cells, but they trans-stimulated 6-CF and [(3)H]ES uptake, indicating an
      asymmetric interaction of hOAT4 with these substrates. In chloride-free medium,
      HEK293-hOAT4-mediated [(3)H]PAH efflux was almost abolished, whereas addition of
      ES restored it comparable to Ringer solution, consistent with a physiologic
      ES/PAH or PAH/Cl(-) exchange mode of hOAT4. Moreover, an acidification of the
      uptake medium increased 6-CF as well as [(3)H]ES uptake, which was reduced by
      nigericin, suggesting that hOAT4 also can operate as an OA/OH(-) exchanger. hOAT4
      facilitates substantial uptake of [(14)C]urate, which was elevated 2.6-fold by
      intracellular HCTZ. Thus, hOAT4 is the long-postulated, low-affinity apical urate
      anion exchanger that facilitates HCTZ-associated hyperuricemia.

PMID- 17229914
TI  - Chronic kidney disease: common, harmful, and treatable--World Kidney Day 2007.

PMID- 17229913
TI  - Angiotensin II type 1 receptor blockade inhibits the development and progression
      of HIV-associated nephropathy in a mouse model.
AB  - HIV-associated nephropathy (HIVAN) is characterized by a collapsed glomerular
      capillary tuft with hyperplasia and hypertrophy of podocytes. Recently generated
      were conditional transgenic mice (podocin/Vpr) that express one of the HIV-1
      accessory genes, vpr, selectively in podocytes using podocin promoter and Tet-on
      system. These transgenic mice developed renal injury similar to HIVAN when
      treated with doxycycline for 8 to 12 wk. This study demonstrated that nephron
      reduction by heminephrectomy markedly enhanced phenotypic changes of podocytes
      and led to severe FSGS within 4 wk. Nephrotic-range proteinuria was observed
      already at 2 wk, together with dedifferentiation and dysregulation of podocytes,
      indicated by decreased expression of nephrin, synaptopodin, and Wilms' tumor 1
      protein and increased expression of Ki-67. The acceleration of phenotypic changes
      of podocytes, proteinuria, and subsequent glomerulosclerosis by heminephrectomy
      was almost completely inhibited by angiotensin II type 1 receptor (AT1R) blocker
      olmesartan. In contrast, the renoprotective effect of the calcium channel
      antagonist azelnidipine was minimal, although it lowered systemic BP to the same
      level as olmesartan, demonstrating that the inhibitory effect of AT1R blocker was
      independent of systemic BP. Olmesartan also reduced proteinuria and prevented
      glomerulosclerosis even by the delayed treatment, which was initiated after the
      podocyte injury appeared. These data suggest that nephron reduction exaggerates
      podocyte injury and subsequent glomerulosclerosis, possibly through glomerular
      hypertension, in the mouse model of HIVAN. AT1R blockade could be beneficial in
      the treatment of HIVAN by ameliorating podocyte injury by avoiding the vicious
      cycle of nephron reduction and glomerular hypertension.

PMID- 17229915
TI  - Unrestricted C3 activation occurs in Crry-deficient kidneys and rapidly leads to
      chronic renal failure.
AB  - Deficiency of the C3 convertase regulator Crry is embryonic lethal in mice unless
      C3 also is absent. For evaluation of the effect of local kidney Crry deficiency
      in the setting of an intact complement system, Crry(-/-)C3(-/-) mouse kidneys
      were transplanted into syngeneic C57BL/6 wild-type mice. These Crry-deficient
      kidneys developed marked inflammatory cell infiltration, tubular damage, and
      interstitial fibrosis, whereas similar changes were absent in control
      transplanted kidneys. Strong C3 deposition in the vessels and tubules that
      correlated significantly with measures of disease supported that complement
      activation was pathogenic in this model. Microarray studies showed upregulation
      of a number of chemokine and extracellular matrix genes, which were validated for
      CCL2 and CXCL10 mRNA and collagen III protein. The functional significance of
      these pathophysiologic findings was evaluated by removing both native kidneys, so
      the transplanted kidney alone provided renal function. Within 21 d of
      transplantation, seven of eight Crry-deficient kidneys in complement-sufficient
      wild-type hosts failed, compared with two of 13 controls (P = 0.001), with final
      blood urea nitrogen levels of 133.9 +/- 33.0 and 55.6 +/- 8.3 mg/dl, respectively
      (P = 0.015). These data show that mouse Crry is a critical complement regulator
      in the kidney. When absent, unrestricted complement activation occurs and quickly
      leads to marked inflammation and progressive renal failure, with features
      relevant to human diseases with underlying defects in complement regulation, such
      as hemolytic uremic syndrome.

PMID- 17229916
TI  - Hemolytic uremic syndrome: a factor H mutation (E1172Stop) causes defective
      complement control at the surface of endothelial cells.
AB  - Defective complement regulation results in hemolytic uremic syndrome (HUS), a
      disease that is characterized by microangiopathy, thrombocytopenia, and acute
      renal failure and that causes endothelial cell damage. For characterization of
      how defective complement regulation relates to the pathophysiology, the role of
      the complement regulator factor H and also of a mutant factor H protein was
      studied on the surface of human umbilical vein endothelial cells. The mutant 145
      kD factor H protein was purified to homogeneity, from plasma of a patient with
      HUS, who is heterozygous for a factor H gene mutation G3587T, which introduces a
      stop codon at position 1172. Functional analyses show that the lack of the most C
      terminal domain short consensus repeats 20 severely affected recognition
      functions (i.e., binding to heparin, C3b, C3d, and the surface of endothelial
      cells). Wild-type factor H as well as the mutant protein formed dimers in
      solution as shown by cross-linking studies and mass spectroscopy. When assayed in
      fluid phase, the complement regulatory activity of the mutant protein was normal
      and comparable to wild-type factor H. However, on the surface of endothelial
      cells, the mutant factor H protein showed severely reduced regulatory activities
      and lacked protective functions. Similarly, with the use of sheep erythrocytes,
      the mutant protein lacked the protective activity and caused increased hemolysis
      when it was added to factor H-depleted plasma. This study shows how a mutation
      that affects the C-terminal region of the factor H protein leads to defective
      complement control on cell surfaces and damage to endothelial cells in patients
      with HUS. These effects explain how mutant factor H causes defective complement
      control and in HUS-particularly under condition of inflammation and complement
      activation-causes endothelial cell damage.

PMID- 17229917
TI  - Nephrogenic syndrome of inappropriate antidiuresis in adults: high phenotypic
      variability in men and women from a large pedigree.
AB  - Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a recently
      described genetic cause of hyponatremia in male infants. Whether this X-linked
      condition could be detected in the adult or also could affect women is unknown. A
      large five-generation family was identified in which the recently described
      arginine-vasopressin receptor type 2 (AVPR2) mutation that is responsible for
      NSIAD was segregated. The proband was a 74-yr-old patient who had a syndrome of
      inappropriate antidiuresis and whose hyponatremia resisted administration of two
      AVPR2 antagonists. The phenotype of family members who carry the mutation was
      investigated. Patients with normal serum sodium were subjected to a water-load
      test. The previously reported activating missense R137C mutation in the AVPR2
      gene in three hemizygous male and four heterozygous female individuals was
      identified. Except in one woman, spontaneous episodes of hyponatremia or abnormal
      water-load test were identified in all patients with the mutation, whether male
      or female. Skewed X inactivation was evidenced in the blood of the asymptomatic
      woman, which is compatible with preferential inactivation of her mutated allele.
      NSIAD is not limited to male infants. The diagnosis also should be considered in
      both male and female adults.

PMID- 17229918
TI  - Iron regulation.

PMID- 17229919
TI  - Genotype-phenotype study in an FSHD family with a proximal deletion encompassing
      p13E-11 and D4Z4.
AB  - BACKGROUND: In the majority of facioscapulohumeral muscular dystrophy (FSHD)
      cases, the molecular basis of the disease is due to loss of subtelomeric D4Z4
      repeat units at 4q35. Occasionally, an apparent absence of the contracted D4Z4
      repeat is associated with FSHD. One explanation for this finding is a deletion in
      the region proximal to the D4Z4 repeat array that encompasses the p13E-11
      (D4F104S1) probe-binding site used in the DNA diagnosis. The frequency of such
      proximally extended deletions is unknown, and to date, few patients have been
      described due to the difficulties in the molecular identification of such cases.
      METHODS: We describe a family (DUK 2531) in which a contracted D4Z4 allele and a
      large proximal deletion of approximately 75 kb are segregating to 11 individuals.
      This is the largest deletion identified to date. Family DUK 2531 was initially
      thought to have normal D4Z4 fragment size and therefore unlinked to the 4q35
      region (FSHD1B). RESULTS: Further molecular analysis of DUK 2531 reveals the
      presence of 10 repeat units (33 kb). The extended deletion includes the probe
      p13E-11 and B31 binding sites, the inverted repeat D4S2463, and genes FRG2 and
      TUBB4Q. CONCLUSION: Despite the length of the proximal deletion in this family,
      the range and severity of the clinical manifestations are typical for the
      disorder. Because such deletions can lead to misinterpretation in the diagnostic
      setting, this suggests the need for additional diagnostic tests in
      facioscapulohumeral muscular dystrophy.

PMID- 17229920
TI  - SCN organization reconsidered.
AB  - The SCN has long had organizational schemas imposed on it. In most, the SCN is
      dichotomized, with one region typically associated with the presence of
      vasopressin cells and the other associated with cells containing vasoactive
      intestinal polypeptide and certain afferent terminal fields. If assumed to be
      accurate, the schemas that have been intended to simplify and conceptually
      organize the known anatomy may actually interfere with the understanding of how
      various cell types and input pathways contribute to circadian rhythm regulation.
      This review describes inadequacies of existing schemas and notes several
      practical difficulties that undermine their usefulness. These include "static"
      versus "dynamic" anatomy, generalizations about SCN organization in relation to
      the plane or level of section, and the concept of differential density, all of
      which contribute to a view in which the SCN is substantially more complex than
      typically depicted in oversimplified line drawings. The need for accurate
      topographical description is emphasized.

PMID- 17229922
TI  - Gate cells see the light.

PMID- 17229921
TI  - Gates and oscillators II: zeitgebers and the network model of the brain clock.
AB  - Circadian rhythms in physiology and behavior are regulated by the SCN. When
      assessed by expression of clock genes, at least 2 distinct functional cell types
      are discernible within the SCN: nonrhythmic, light-inducible, retinorecipient
      cells and rhythmic autonomous oscillator cells that are not directly
      retinorecipient. To predict the responses of the circadian system, the authors
      have proposed a model based on these biological properties. In this model, output
      of rhythmic oscillator cells regulates the activity of the gate cells. The gate
      cells provide a daily organizing signal that maintains phase coherence among the
      oscillator cells. In the absence of external stimuli, this arrangement yields a
      multicomponent system capable of producing a self-sustained consensus rhythm.
      This follow-up study considers how the system responds when the gate cells are
      activated by an external stimulus, simulating a response to an entraining (or
      phase-setting) signal. In this model, the authors find that the system can be
      entrained to periods within the circadian range, that the free-running system can
      be phase shifted by timed activation of the gate, and that the phase response
      curve for activation is similar to that observed when animals are exposed to a
      light pulse. Finally, exogenous triggering of the gate over a number of days can
      organize an arrhythmic system, simulating the light-dependent reappearance of
      rhythmicity in a population of disorganized, independent oscillators. The model
      demonstrates that a single mechanism (i.e., the output of gate cells) can account
      for not only free-running and entrained rhythmicity but also other circadian
      phenomena, including limits of entrainment, a PRC with both delay and advance
      zones, and the light-dependent reappearance of rhythmicity in an arrhythmic
      animal.

PMID- 17229923
TI  - Hofbauer-Buchner eyelet affects circadian photosensitivity and coordinates TIM
      and PER expression in Drosophila clock neurons.
AB  - Extraretinal photoreception is a common input route for light resetting signals
      into the circadian clock of animals. In Drosophila melanogaster, substantial
      circadian light inputs are mediated via the blue light photoreceptor CRYPTOCHROME
      (CRY) expressed in clock neurons within the brain. The current model predicts
      that, upon light activation, CRY interacts with the clock proteins TIMELESS (TIM)
      and PERIOD (PER), thereby inducing their degradation, which in turn leads to a
      resetting of the molecular oscillations within the circadian clock. Here the
      authors investigate the function of another putative extraretinal circadian
      photoreceptor, the Hofbauer-Buchner eyelet (H-B eyelet), located between the
      retina and the medulla in the fly optic lobes. Blocking synaptic transmission
      between the H-B eyelet and its potential target cells, the ventral circadian
      pacemaker neurons, impaired the flies' ability to resynchronize their behavior
      under jet-lag conditions in the context of nonfunctional retinal photoreception
      and a mutation in the CRY-encoding gene. The same manipulation also affected
      synchronized expression of the clock proteins TIM and PER in different subsets of
      the clock neurons. This shows that synaptic communication between the H-B eyelet
      and clock neurons contributes to synchronization of molecular and behavioral
      rhythms and confirms that the H-B eyelet functions as a circadian photoreceptor.
      Blockage of synaptic transmission from the H-B eyelet in the presence of
      functional compound eyes and the absence of CRY also results in increased numbers
      of flies that are unable to synchronize to extreme photoperiods, supplying
      independent proof for the role of the H-B eyelet as a circadian photoreceptor.

PMID- 17229924
TI  - Circadian rhythms in the mating behavior of the cockroach, Leucophaea maderae.
AB  - Mating behavior of small populations of virgin males and females of the cockroach
      Leucophaea maderae were continuously monitored via time-lapse video recording in
      controlled laboratory conditions. The time of onset of copulation was found to be
      rhythmic in a light cycle of 12 h light alternated with 12 h of darkness, with
      the peak of mating behavior occurring near the light to dark transition. This
      rhythm persisted in constant dim red illumination and constant temperature. In
      constant conditions, the period of the rhythm was slightly less than 24 h, with a
      peak of copulation during the late subjective day. These data demonstrated that
      mating behavior is gated by a circadian clock. When males and females were taken
      from light cycles that were 12 h out of phase, a bimodal rhythm was observed with
      one peak in the males' late subjective day and a second peak of equal amplitude
      in the late subjective day of females. The results indicated that circadian
      systems in both males and females contribute to the circadian rhythm in
      copulation. Bilateral section of the optic tracts (OTX) of both males and females
      abolished the rhythm, but the rhythm persisted when OTX females were paired with
      intact males or when OTX males were paired with intact females. Furthermore, when
      OTX males or OTX females were paired with intact animals that were 12 h out of
      phase, a bimodal rhythm was still observed. These results suggested that the
      circadian pacemaker in the optic lobes of both male and female cockroaches
      participates in the control of mating, but that a pacemaker outside the optic
      lobes is also likely involved. Finally, it was shown that the female's olfactory
      response (measured by electroantennogram) to components of the male sex pheromone
      exhibited a circadian rhythm, but the data suggested the peripheral olfactory
      rhythm is not likely to be involved in the rhythm of mating behavior.

PMID- 17229925
TI  - Bimodal clock gene expression in mouse suprachiasmatic nucleus and peripheral
      tissues under a 7-hour light and 5-hour dark schedule.
AB  - Using the mPer1::luc real-time monitoring technique, the authors observed the
      bimodal patterns of mPer1 bioluminescence on each side of the SCN, in parallel
      with maintaining synchronization between the left and right sides of the SCN
      under an artificial light:dark:light:dark (LDLD) 7:5:7:5 condition. In situ
      hybridization analysis of mPer1 and mBmal1 mRNA distribution in the SCN showed
      that in 1 photophase (morning photophase; M) of LDLD, the mPer1 level in the
      ventrolateral-like (VL-like) subdivision of the SCN was higher than that in the
      dorsomedial-like (DM-like) subdivision, and this regional distribution pattern
      was reversed in another photophase (evening photophase; E). In contrast, the
      mBmal1 level was higher in the DM-like subdivision than in the VL-like
      subdivision in the M phase, and this distribution changed in the E phase. The
      prokineticin 2 (PK2) mRNA that encodes an SCN output molecule that is thought to
      transmit the circadian locomotor rhythms was reduced in both the DM-like and VL
      like SCN and did not clearly correlate with the activity under the LDLD
      condition. The expression of mPer1 and mPer2 in the liver was clearly bimodal,
      whereas the expressions of other clock genes were not synchronized to the LDLD
      condition. These results may provide important insights into the mechanism
      underlying the splitting or bimodal rhythms that may in turn facilitate the
      understanding of the ability to measure the seasonal day length in mammals.

PMID- 17229926
TI  - A mathematical model for the Kai-protein-based chemical oscillator and clock gene
      expression rhythms in cyanobacteria.
AB  - In the cyanobacterium, Synechococcus elongatus, most promoters are regulated by a
      circadian clock under continuous light (LL) conditions. Nevertheless, the basic
      circadian oscillation is primarily generated by alternating KaiC
      phosphorylation/dephosphorylation reactions at the posttranslational level.
      Indeed, the KaiC phosphorylation cycle was recently reconstituted in vitro by
      incubating KaiA, KaiB, and KaiC proteins with ATP. However, the molecular
      dynamics of this chemical oscillation and the mechanism that drives the circadian
      transcription/translation rhythms remain unknown. In this report, the KaiC
      phosphorylation cycle and the gene regulatory network in the cyanobacterial
      circadian system have been modeled. The model reproduces the robust KaiC
      phosphorylation cycle in the absence of de novo gene expression as is observed in
      vitro, as well as its coupling to transcriptional/translational feedback in LL
      conditions in vivo. Moreover, the model is consistent with most previous
      experiments, including various combinations of genetic knockout or overexpression
      of kai genes. It also predicts that multiple KaiC phosphorylation states and
      dynamic Kai protein interactions may be required for the cyanobacterial circadian
      system.

PMID- 17229927
TI  - PER1-like immunoreactivity in oxytocin cells of the hamster hypothalamo
      neurohypophyseal system.

PMID- 17229928
TI  - Transient, light-induced rhythmicity in mPer-deficient mice.

PMID- 17229929
TI  - Proliferation of adult sertoli cells following conditional knockout of the Gap
      junctional protein GJA1 (connexin 43) in mice.
AB  - GJA1 (also known and referred to here as connexin 43 and abbreviated CX43) is the
      predominant testicular gap junction protein, and CX43 may regulate Sertoli cell
      maturation and spermatogenesis. We hypothesized that lack of CX43 would inhibit
      Sertoli cell differentiation and extend proliferation. To test this, a Sertoli
      cell-specific Cx43 knockout (SC-Cx43 KO) mouse was generated using Cre-lox
      technology. Immunohistochemistry indicated that CX43 was not expressed in the
      Sertoli cells of SC-Cx43 KO mice, but was normal in organs such as the heart.
      Testicular weight was reduced by 41% and 76% in SC-Cx43 KO mice at 20 and 60
      days, respectively, vs. wild-type (wt) mice. Seminiferous tubules of SC-Cx43 KO
      mice contained only Sertoli cells and actively proliferating early spermatogonia.
      Sertoli cells normally cease proliferation at 2 wk of age in mice and become
      terminally differentiated. However, proliferating Sertoli cells were present in
      SC-Cx43 KO but not wt mice at 20 and 60 days of age. Thyroid hormone receptor
      alpha (THRA) is high in proliferating Sertoli cells, then declines sharply in
      adulthood. Thra mRNA expression was increased in 20-day SC-Cx43 KO vs. wt mice,
      and it showed a trend toward an increase in 60-day mice, indicating that loss of
      CX43 in Sertoli cells inhibited their maturation. In conclusion, we have
      generated mice lacking CX43 in Sertoli cells but not other tissues. Our data
      indicate that CX43 in Sertoli cells is essential for spermatogenesis but not
      spermatogonial maintenance/proliferation. SC-Cx43 KO mice showed continued
      Sertoli cell proliferation and delayed maturation in adulthood, indicating that
      CX43 plays key roles in Sertoli cell development.

PMID- 17229930
TI  - Male germ line stem cells have an altered potential to proliferate and
      differentiate during postnatal development in mice.
AB  - Spermatogonial stem cells (SSCs) continuously support spermatogenesis after
      puberty. However, accumulating evidence suggests that SSCs differ functionally
      during postnatal development. For example, mutant mice exist in which SSCs
      support spermatogenesis in the first wave after birth but cease to do so
      thereafter, resulting in infertility in adults. Studies using a retroviral vector
      have shown that the vector transduces pup SSCs more efficiently than adult SSCs,
      which suggests that pup SSCs divide more frequently. Thus, it is hypothesized
      that the SSCs in pup and adult testes have different characteristics. As an
      approach to testing this hypothesis in the present study, we investigated the
      proliferation kinetics of pup SSCs (6-9 days old) and their self
      renewal/differentiation patterns for the first 2 mo after transplantation, and
      compared them to those of adult SSCs. Using serial transplantation, we found that
      the number of pup SSCs declined over the first week after transplantation.
      Thereafter, it increased ~4-fold by 1 mo and ~9-fold by 2 mo after
      transplantation, which indicates that pup SSCs continuously proliferate from 1 wk
      to 2 mo after transplantation. Compared to the proliferation of SSCs derived from
      adult intact testes, that of pup SSCs was lower at 1 mo but similar at 2 mo,
      indicating the delayed proliferation of pup SSCs. However, the pup SSCs
      regenerated spermatogenic colonies at 1 mo that were similar in length to those
      of SSCs from adult intact testes. Therefore, these results suggest that some
      functional differences exist in SSCs during postnatal development, and that these
      differences may affect the abilities of SSCs to self-renew and differentiate.

PMID- 17229931
TI  - The cathepsin L first intron stimulates gene expression in rat sertoli cells.
AB  - Large amounts of cathepsin L (CTSL), a cysteine protease required for
      quantitatively normal spermatogenesis, are synthesized by mouse and rat Sertoli
      cells during stages VI to VII of the cycle of the seminiferous epithelium. We
      previously demonstrated that all of the regulatory elements required in vivo for
      both Sertoli cell- and stage-specific expression of the Ctsl gene are present
      within a ~3-kb genomic fragment that contains 2065 nucleotides upstream of the
      transcription start site and 977 nucleotides of downstream sequence. Most of the
      downstream region encodes the first intron. In this study, transient transfection
      assays using primary Sertoli cell cultures and the TM4 Sertoli cell line
      established that the Ctsl first intron increased reporter gene activity by ~5
      fold. While the intron-mediated enhancement in reporter gene activity was not
      restricted to the Ctsl promoter, positioning the first intron upstream of the
      Ctsl promoter in either orientation abolished its stimulatory activity,
      suggesting that it does not contain a typical enhancer. Mutating the 5'-splice
      site of the Ctsl first intron or replacing the first intron by the Ctsl fourth
      intron abolished the stimulatory effect. Finally, the intron-dependent increase
      in reporter gene activity could be explained in part by an increase in the
      amounts of total RNA and transcript polyadenylation. Results from this study
      suggest that the stimulatory effect mediated by the Ctsl first intron may explain
      in part why Sertoli cells in seminiferous tubules at stages VI to VII produce
      high levels of CTSL.

PMID- 17229932
TI  - Cyclosporin a improves pregnancy outcome by promoting functions of trophoblasts
      and inducing maternal tolerance to the allogeneic fetus in abortion-prone matings
      in the mouse.
AB  - The embryo expresses paternal antigens foreign to the mother, and therefore has
      been viewed as a natural allograft. Cyclosporin A (CsA) is an immunosuppressant
      for preventing allograft rejection. Little is known, however, about the
      modulating effect of CsA on the materno-fetal relationship. In this study,
      pregnant CBA/J female mice mated with DBA/2 or BALB/c male mice as abortion-prone
      and normal pregnancy matings were administered, respectively, with CsA at Day 4
      of gestation. We demonstrated that the administration of CsA at the window of
      implantation resulted in maternal T-cell tolerance to paternal antigen, and it
      improved pregnancy outcome in the CBA/J multiply sign in box DBA/2 abortion-prone
      matings. CsA administration enhanced Th2 and reduced Th1 cytokine production at
      the materno-fetal interface, and it expanded peripheral CD4(+)CD25(+) FOXP3(+)
      regulatory T cells in abortion-prone matings, implying development of Th2 bias
      and regulatory T cells. On the other hand, we observed that treatment with CsA
      led to enhanced growth and invasiveness of trophoblasts in the abortion-prone
      matings. Together, these findings indicate that CsA in lower dosages can induce
      materno-fetal tolerance and improve the biologic functions of trophoblast cells
      in the abortion-prone matings, leading to a successful pregnancy, which is useful
      in clinical therapeutics for spontaneous pregnancy wastage and other pregnancy
      complications.

PMID- 17229933
TI  - Redox regulation of sperm surface thiols modulates adhesion to the fallopian tube
      epithelium.
AB  - Sperm that adhere to the fallopian tube epithelium are of superior quality and
      adhesion extends their fertile life. It has been postulated that periovulatory
      signals, as yet undefined, promote sperm release. In the in vitro studies
      described here, we examined the effects of several antioxidants, reportedly
      present within oviductal fluid, on the modulation of sperm-oviduct adhesion in
      bovine species. Results showed that 1) the cell-permeant thiols (penicillamine,
      beta mercaptoethanol, cysteine, and dithiotreitol), as well as the nonpermeant
      thiol, reduced glutathione, cause adhering spermatozoa to release from the
      epithelium; 2) thiol action is exerted on spermatozoa; and 3) oxidized
      glutathione, as well as the non-thiol antioxidants (dimethylthiourea, trolox,
      superoxide dismutase, and catalase) have no effect. Sperm surface sulfhydryls
      labeled with iodoacetamide fluorescein showed that spermatozoa devoid of
      sulfhydryls on the head surface adhered to the fallopian epithelium in vitro,
      whereas thiol-induced release increased the exposure of sulfhydryls on the sperm
      head surface. Finally, analysis of capacitation status demonstrated that
      uncapacitated spermatozoa adhered to the oviduct, and that thiol-induced release
      of spermatozoa was accompanied by capacitation. In conclusion, thiol-reducing
      agents in the oviductal fluid may modulate the redox status of sperm surface
      proteins, leading to the release of spermatozoa selected and stored through
      adhesion to the fallopian tube epithelium in the bovine species.

PMID- 17229934
TI  - 2-methoxyestradiol induces spindle aberrations, chromosome congression failure,
      and nondisjunction in mouse oocytes.
AB  - 2-Methoxyestradiol (2-ME) is a metabolite of 17beta-estradiol and a natural
      component of follicular fluid. Local concentrations of 2-ME may be increased by
      exposure to environmental pollutants that activate the expression of enzymes in
      the metabolic pathway from 17beta-estradiol to 2-ME. It has been suspected that
      this may have adverse effects on spindle formation in maturing oocytes, which
      would affect embryo quality. To study the dose-response patterns, we exposed
      denuded mouse oocytes to 2-ME during in vitro maturation. Meiotic progression,
      spindle morphology, centrosome integrity, and chromosome congression were
      examined by immunofluorescence and noninvasive polarizing microscopy (PolScope).
      Chromosomal constituents were assessed after spreading and C-banding. 2-ME
      sustained MAD2L1 expression at the centromeres and increased the number of
      meiosis I-blocked oocytes in a dose-dependent manner. 2-ME also caused dramatic
      dose-dependent increases in the hyperploidy of metaphase II oocytes. Some of
      these meiosis II oocytes contained anaphase I-like chromosomes, which suggests
      that high concentrations of the catecholestradiol interfere with the physical
      separation of chromosomes. Noninvasive PolScope analysis and tubulin
      immunofluorescence revealed that perturbations in spindle organization, which
      resulted in severe disturbances of the chromosome alignment at the spindle
      equator (congression failure), were caused by 2-ME at meiosis I and II.
      Pericentrin-positive centrosomes failed to align at the spindle poles, and
      multipolar spindles and prominent arrays of cytoplasmic microtubule asters were
      induced in 2-ME-exposed metaphase II oocytes. In conclusion, a micromolar level
      of 2-ME is aneugenic for mammalian oocytes. Therefore, exposure to 2-ME and
      conditions that increase the intrinsic local concentration of 2-ME in the ovary
      may affect fertility and increase risks for chromosomal aberrations in the oocyte
      and embryo.

PMID- 17229935
TI  - Expression pattern of prokineticin 1 and its receptors in bovine ovaries during
      the estrous cycle: involvement in corpus luteum regression and follicular
      atresia.
AB  - Prokineticin 1 (PROK1), also termed endocrine gland-derived vascular endothelial
      growth factor (endocrine gland-derived VEGF), is a newly identified protein
      assigned with diverse biologic functions. It binds two homologous G protein
      coupled receptors, PROKR1 and PROKR2. To better understand the roles of PROK1 and
      its receptors in ovarian function, their expression was determined in follicles
      and corpora lutea (CLs) at different developmental stages. PROK1 mRNA levels were
      low at early luteal stage and midluteal stage, but increased sharply during
      natural or induced luteolysis. High PROK1 mRNA levels also were found in atretic
      follicles. This profile of PROK1 expression was opposite to that of the well
      established angiogenic factor VEGF. Of the two receptor-type expressions, PROKR1
      but not PROKR2 was correlated positively with its ligand. Immunohistochemical
      staining revealed that PROK1 was located mainly within the muscular layer of
      arterioles, and during regression it also was localized to macrophages and
      steroidogenic cells. The expression pattern of ITGB2 mRNA, a leukocyte cell
      marker, overlapped that of PROK1, thus suggesting that leukocyte infiltration may
      explain the elevated expression of PROK1 in atretic follicles and regressing CL.
      Indeed, flow cytometry analyses showed that nearly all beta-2 integrin chain
      (ITGB2)-positive cells also were stained with anti-PROK1 and that significantly
      more ITGB2/PROK1 double-stained cells were present in degenerating follicles and
      CL. Furthermore, when challenged in vitro with PROK1, adherent, mononuclear cell
      numbers and TNF levels were elevated, indicating that PROK1 triggers monocyte
      activation. Together, these data suggest that PROK1, acting via PROKR1, may be
      involved in the recruitment of monocytes to regressing CL and atretic follicles
      and their consequent activation therein.

PMID- 17229936
TI  - Chronic treatment with sildenafil improves energy balance and insulin action in
      high fat-fed conscious mice.
AB  - Stimulation of nitric oxide-cGMP signaling results in vascular relaxation and
      increased muscle glucose uptake. We show that chronically inhibiting cGMP
      hydrolysis with the phosphodiesterase-5 inhibitor sildenafil improves energy
      balance and enhances in vivo insulin action in a mouse model of diet-induced
      insulin resistance. High-fat-fed mice treated with sildenafil plus L-arginine or
      sildenafil alone for 12 weeks had reduced weight and fat mass due to increased
      energy expenditure. However, uncoupling protein-1 levels were not increased in
      sildenafil-treated mice. Chronic treatment with sildenafil plus L-arginine or
      sildenafil alone increased arterial cGMP levels but did not adversely affect
      blood pressure or cardiac morphology. Sildenafil treatment, with or without l
      arginine, resulted in lower fasting insulin and glucose levels and enhanced rates
      of glucose infusion, disappearance, and muscle glucose uptake during a
      hyperinsulinemic (4 mU x kg(-1) x min(-1))-euglycemic clamp in conscious mice.
      These effects occurred without an increase in activation of muscle insulin
      signaling. An acute treatment of high fat-fed mice with sildenafil plus l
      arginine did not improve insulin action. These results show that
      phosphodiesterase-5 is a potential target for therapies aimed at preventing diet
      induced energy imbalance and insulin resistance.

PMID- 17229937
TI  - Effects of diazoxide on gene expression in rat pancreatic islets are largely
      linked to elevated glucose and potentially serve to enhance beta-cell
      sensitivity.
AB  - Diazoxide enhances glucose-induced insulin secretion from beta-cells through
      mechanisms that are not fully elucidated. Here, we used microarray analysis
      (Affymetrix) to investigate effects of diazoxide. Pancreatic islets were cultured
      overnight at 27, 11, or 5.5 mmol/l glucose with or without diazoxide. Inclusion
      of diazoxide upregulated altogether 211 genes (signal log(2) ratio > or =0.5) and
      downregulated 200 genes (signal log(2) ratio -0.5 or lower), and 92% of
      diazoxide's effects (up- and downregulation) were observed only after coculture
      with 11 or 27 mmol/l glucose. We found that 11 mmol/l diazoxide upregulated 97
      genes and downregulated 21 genes. Increasing the glucose concentration to 27
      mmol/l markedly shifted these proportions toward downregulation (101 genes
      upregulated and 160 genes downregulated). At 27 mmol/l glucose, most genes
      downregulated by diazoxide were oppositely affected by glucose (80%). Diazoxide
      influenced expression of several genes central to beta-cell metabolism. Diazoxide
      downregulated genes of fatty acid oxidation, upregulated genes of fatty acid
      synthesis, and downregulated uncoupling protein 2 and lactic acid dehydrogenase.
      Diazoxide upregulated certain genes known to support beta-cell functionality,
      such as NKX6.1 and PDX1. Long-term elevated glucose is permissive for most of
      diazoxide's effects on gene expression, the proportion of effects shifting to
      downregulation with increasing glucose concentration. Effects of diazoxide on
      gene expression could serve to enhance beta-cell functionality during continuous
      hyperglycemia.

PMID- 17229938
TI  - Defective insulin and acetylcholine induction of endothelial cell-nitric oxide
      synthase through insulin receptor substrate/Akt signaling pathway in aorta of
      obese rats.
AB  - The actions of acetylcholine (ACh) on endothelium mainly are mediated through
      muscarinic receptors, which are members of the G protein-coupled receptor family.
      In the present study, we show that ACh induces rapid tyrosine phosphorylation and
      activation of Janus kinase 2 (JAK2) in rat aorta. Upon JAK2 activation, tyrosine
      phosphorylation of insulin receptor substrate (IRS)-1 is detected. In addition,
      ACh induces JAK2/IRS-1 and IRS-1/phosphatidylinositol (PI) 3-kinase associations,
      downstream activation of Akt/protein kinase B, endothelial cell-nitric oxide
      synthase (eNOS), and extracellular signal-regulated kinase (ERK)-1/2. The
      pharmacological blockade of JAK2 or PI 3-kinase reduced ACh-stimulated eNOS
      phosphorylation, NOS activity, and aorta relaxation. These data indicate a new
      signal transduction pathway for IRS-1/PI 3-kinase/Akt/eNOS activation and ERK1/2
      by means of JAK2 tyrosine phosphorylation stimulated by ACh in vessels. Moreover,
      we demonstrate that in aorta of obese rats (high-fat diet), there is an
      impairment in the insulin- and ACh-stimulated IRS-1/PI 3-kinase pathway, leading
      to reduced activation with lower protein levels of eNOS associated with a
      hyperactivated ERK/mitogen-activated protein kinase pathway. These results
      suggest that in aorta of obese rats, there not only is insulin resistance but
      also ACh resistance, probably mediated by a common signaling pathway that
      controls the activity and the protein levels of eNOS.

PMID- 17229939
TI  - SUMO4 M55V variant is associated with diabetic nephropathy in type 2 diabetes.
AB  - OBJECTIVE-SUMO4 mRNA was recently found to be mainly expressed in the kidney, and
      the methionine-to-valine substitution at codon 55 (M55V) variant of SUMO4 may
      induce higher nuclear factor-kappaB (NF-kappaB) activity. Because NF-kappaB is
      known to mediate the development of diabetic nephropathy, we examined the
      association between the SUMO4 M55V variant and the severity of diabetic
      nephropathy. RESEARCH DESIGN AND METHODS-We recruited a total of 430 patients
      with type 2 diabetes. The M55V (rs237025, 163A-->G) polymorphism of SUMO4 was
      genotyped by real-time PCR, and urine albumin concentration was measured by
      radioimmunoassay. RESULTS-The frequencies of SUMO4 AA, GA, and GG were 52.6,
      40.7, and 6.7%, respectively, in the normoalbuminuric group; 45.5, 47.3, and 7.1%
      in the microalbuminuric group; and 36.9, 46.2, and 16.9% in the macroalbuminuric
      group. We detected a significant linear trend for SUMO4 genotype between the
      macroalbuminuric and normoalbuminuric groups. The mean urine albumin-to
      creatinine ratio (42.3 +/- 108.82 mg/mmol) in the GG group was significantly
      higher than in the AA (14.9 +/- 51.49 mg/mmol) and GA (17.0 +/- 43.74 mg/mmol)
      groups. Multivariate logistic regression analysis showed the SUMO4 M55V variant
      to be independently associated with the severity of diabetic nephropathy.
      CONCLUSIONS-This study indicates that the SUMO4 gene M55V variant is associated
      with severity of diabetic nephropathy in patients with type 2 diabetes.

PMID- 17229940
TI  - Novel function of the ciliogenic transcription factor RFX3 in development of the
      endocrine pancreas.
AB  - The transcription factor regulatory factor X (RFX)-3 regulates the expression of
      genes required for the growth and function of cilia. We show here that mouse RFX3
      is expressed in developing and mature pancreatic endocrine cells during
      embryogenesis and in adults. RFX3 expression already is evident in early Ngn3
      positive progenitors and is maintained in all major pancreatic endocrine cell
      lineages throughout their development. Primary cilia of hitherto unknown function
      present on these cells consequently are reduced in number and severely stunted in
      Rfx3(-/-) mice. This ciliary abnormality is associated with a developmental
      defect leading to a uniquely altered cellular composition of the islets of
      Langerhans. Just before birth, Rfx3(-/-) islets contain considerably less insulin
      , glucagon-, and ghrelin-producing cells, whereas pancreatic polypeptide-positive
      cells are markedly increased in number. In adult mice, the defect leads to small
      and disorganized islets, reduced insulin production, and impaired glucose
      tolerance. These findings suggest that RFX3 participates in the mechanisms that
      govern pancreatic endocrine cell differentiation and that the presence of primary
      cilia on islet cells may play a key role in this process.

PMID- 17229941
TI  - Effects of palmitate on Ca(2+) handling in adult control and ob/ob
      cardiomyocytes: impact of mitochondrial reactive oxygen species.
AB  - Obesity and insulin resistance are associated with enhanced fatty acid
      utilization, which may play a central role in diabetic cardiomyopathy. We now
      assess the effect of the saturated fatty acid palmitate (1.2 mmol/l) on Ca(2+)
      handling, cell shortening, and mitochondrial production of reactive oxygen
      species (ROS) in freshly isolated ventricular cardiomyocytes from normal (wild
      type) and obese, insulin-resistant ob/ob mice. Cardiomyocytes were electrically
      stimulated at 1 Hz, and the signal of fluorescent indicators was measured with
      confocal microscopy. Palmitate decreased the amplitude of cytosolic Ca(2+)
      transients (measured with fluo-3), the sarcoplasmic reticulum Ca(2+) load, and
      cell shortening by approximately 20% in wild-type cardiomyocytes; these decreases
      were prevented by the general antioxidant N-acetylcysteine. In contrast,
      palmitate accelerated Ca(2+) transients and increased cell shortening in ob/ob
      cardiomyocytes. Application of palmitate rapidly dissipated the mitochondrial
      membrane potential (measured with tetra-methyl rhodamine-ethyl ester) and
      increased the mitochondrial ROS production (measured with MitoSOX Red) in wild
      type but not in ob/ob cardiomyocytes. In conclusion, increased saturated fatty
      acid levels impair cellular Ca(2+) handling and contraction in a ROS-dependent
      manner in normal cardiomyocytes. Conversely, high fatty acid levels may be vital
      to sustain cardiac Ca(2+) handling and contraction in obesity and insulin
      resistant conditions.

PMID- 17229942
TI  - Dietary energy density is associated with obesity and the metabolic syndrome in
      U.S. adults.
AB  - OBJECTIVE: Rising obesity rates have been linked to the consumption of energy
      dense diets. We examined whether dietary energy density was associated with
      obesity and related disorders including insulin resistance and the metabolic
      syndrome. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study using
      nationally representative data of U.S. adults > or =20 years of age from the 1999
      2002 National Health and Nutrition Examination Survey (n = 9,688). Dietary energy
      density was calculated based on foods only. We used a series of multivariate
      linear regression models to determine the independent association between dietary
      energy density, obesity measures (BMI [in kilograms per meters squared] and waist
      circumference [in centimeters]), glycemia, or insulinemia. We used multivariate
      Poisson regression models to determine the independent association between
      dietary energy density and the metabolic syndrome as defined by the National
      Cholesterol and Education Program (Adult Treatment Panel III). RESULTS: Dietary
      energy density was independently and significantly associated with higher BMI in
      women (beta = 0.44 [95% CI 0.14-0.73]) and trended toward a significant
      association in men (beta = 0.37 [-0.007 to 0.74], P = 0.054). Dietary energy
      density was associated with higher waist circumference in women (beta = 1.11
      [0.42-1.80]) and men (beta = 1.33 [0.46-2.19]). Dietary energy density was also
      independently associated with elevated fasting insulin (beta = 0.65 [0.18-1.12])
      and the metabolic syndrome (prevalence ratio = 1.10 [95% CI 1.03-1.17]).
      CONCLUSIONS: Dietary energy density is an independent predictor of obesity,
      elevated fasting insulin levels, and the metabolic syndrome in U.S. adults.
      Intervention studies to reduce dietary energy density are warranted.

PMID- 17229943
TI  - Reduction of surgical mortality and morbidity in diabetic patients undergoing
      cardiac surgery with a combined intravenous and subcutaneous insulin glucose
      management strategy.
AB  - OBJECTIVE: To determine if glucose management in postcardiothoracic surgery
      patients with a combined intravenous (IV) and subcutaneous (SC) insulin regimen
      reduces mortality and morbidity in patients with diabetes and stress-induced
      hyperglycemia. RESEARCH DESIGN AND METHODS: Retrospective review of 614
      consecutive patients who underwent cardiothoracic (CT) surgery in 2005 was
      performed to evaluate the incidence and treatment of postoperative hyperglycemia
      and operative morbidity and mortality. Hyperglycemic patients (glucose >6.05
      mmol/l) were treated with IV insulin in the intensive care unit (ICU) followed by
      SC insulin (outside ICU). Subgroup analysis was performed on 159 coronary artery
      bypass grafting (CABG)-only patients. RESULTS: Among all CT surgeries, patients
      with a preoperative diagnosis of diabetes had higher rates of postoperative
      mortality (7.3 vs. 3.3%; P = 0.03) and pulmonary complications (19.5 vs. 11.6%; P
      = 0.02) but had similar rates of infections and cardiac, renal, and neurological
      complications on univariate analysis. However, on multivariate analysis, a
      preoperative diagnosis of diabetes was not a significant factor in postoperative
      mortality or pulmonary complications. In CABG-only patients, no significant
      differences were seen in outcomes between diabetic and nondiabetic patients.
      Independent of diabetic status, glucose > or =11 mmol/l on ICU admission was
      predictive of higher rates of mortality and renal, pulmonary, and cardiac
      postoperative complications. CONCLUSIONS: A combination of IV insulin (in the
      ICU) and SC insulin (outside the ICU), a less costly and less nursing-intensive
      therapy than 3 days of IV insulin postoperatively, results in a reduction of the
      increased surgical morbidity and mortality in diabetic patients after CT surgery.

PMID- 17229944
TI  - Effect of ruboxistaurin on urinary transforming growth factor-beta in patients
      with diabetic nephropathy and type 2 diabetes.

PMID- 17229945
TI  - Images in clinical medicine. Phlegmasia cerulea dolens.

PMID- 17229946
TI  - Expanding priorities--confronting chronic disease in countries with low income.

PMID- 17229947
TI  - The preventive polypill--much promise, insufficient evidence.

PMID- 17229948
TI  - Obesity and diabetes in the developing world--a growing challenge.

PMID- 17229949
TI  - The prognostic role of a gene signature from tumorigenic breast-cancer cells.
AB  - BACKGROUND: Breast cancers contain a minority population of cancer cells
      characterized by CD44 expression but low or undetectable levels of CD24
      (CD44+CD24-/low) that have higher tumorigenic capacity than other subtypes of
      cancer cells. METHODS: We compared the gene-expression profile of CD44+CD24-/low
      tumorigenic breast-cancer cells with that of normal breast epithelium.
      Differentially expressed genes were used to generate a 186-gene "invasiveness"
      gene signature (IGS), which was evaluated for its association with overall
      survival and metastasis-free survival in patients with breast cancer or other
      types of cancer. RESULTS: There was a significant association between the IGS and
      both overall and metastasis-free survival (P<0.001, for both) in patients with
      breast cancer, which was independent of established clinical and pathological
      variables. When combined with the prognostic criteria of the National Institutes
      of Health, the IGS was used to stratify patients with high-risk early breast
      cancer into prognostic categories (good or poor); among patients with a good
      prognosis, the 10-year rate of metastasis-free survival was 81%, and among those
      with a poor prognosis, it was 57%. The IGS was also associated with the prognosis
      in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01).
      The prognostic power of the IGS was increased when combined with the wound
      response (WR) signature. CONCLUSIONS: The IGS is strongly associated with
      metastasis-free survival and overall survival for four different types of tumors.
      This genetic signature of tumorigenic breast-cancer cells was even more strongly
      associated with clinical outcomes when combined with the WR signature in breast
      cancer.

PMID- 17229950
TI  - Mammographic density and the risk and detection of breast cancer.
AB  - BACKGROUND: Extensive mammographic density is associated with an increased risk
      of breast cancer and makes the detection of cancer by mammography difficult, but
      the influence of density on risk according to method of cancer detection is
      unknown. METHODS: We carried out three nested case-control studies in screened
      populations with 1112 matched case-control pairs. We examined the association of
      the measured percentage of density in the baseline mammogram with risk of breast
      cancer, according to method of cancer detection, time since the initiation of
      screening, and age. RESULTS: As compared with women with density in less than 10%
      of the mammogram, women with density in 75% or more had an increased risk of
      breast cancer (odds ratio, 4.7; 95% confidence interval [CI], 3.0 to 7.4),
      whether detected by screening (odds ratio, 3.5; 95% CI, 2.0 to 6.2) or less than
      12 months after a negative screening examination (odds ratio, 17.8; 95% CI, 4.8
      to 65.9). Increased risk of breast cancer, whether detected by screening or other
      means, persisted for at least 8 years after study entry and was greater in
      younger than in older women. For women younger than the median age of 56 years,
      26% of all breast cancers and 50% of cancers detected less than 12 months after a
      negative screening test were attributable to density in 50% or more of the
      mammogram. CONCLUSIONS: Extensive mammographic density is strongly associated
      with the risk of breast cancer detected by screening or between screening tests.
      A substantial fraction of breast cancers can be attributed to this risk factor.

PMID- 17229951
TI  - Clinical and molecular genetic spectrum of congenital deficiency of the leptin
      receptor.
AB  - BACKGROUND: A single family has been described in which obesity results from a
      mutation in the leptin-receptor gene (LEPR), but the prevalence of such mutations
      in severe, early-onset obesity has not been systematically examined. METHODS: We
      sequenced LEPR in 300 subjects with hyperphagia and severe early-onset obesity,
      including 90 probands from consanguineous families, and investigated the extent
      to which mutations cosegregated with obesity and affected receptor function. We
      evaluated metabolic, endocrine, and immune function in probands and affected
      relatives. RESULTS: Of the 300 subjects, 8 (3%) had nonsense or missense LEPR
      mutations--7 were homozygotes, and 1 was a compound heterozygote. All missense
      mutations resulted in impaired receptor signaling. Affected subjects were
      characterized by hyperphagia, severe obesity, alterations in immune function, and
      delayed puberty due to hypogonadotropic hypogonadism. Serum leptin levels were
      within the range predicted by the elevated fat mass in these subjects. Their
      clinical features were less severe than those of subjects with congenital leptin
      deficiency. CONCLUSIONS: The prevalence of pathogenic LEPR mutations in a cohort
      of subjects with severe, early-onset obesity was 3%. Circulating levels of leptin
      were not disproportionately elevated, suggesting that serum leptin cannot be used
      as a marker for leptin-receptor deficiency. Congenital leptin-receptor deficiency
      should be considered in the differential diagnosis in any child with hyperphagia
      and severe obesity in the absence of developmental delay or dysmorphism.

PMID- 17229952
TI  - Tympanostomy tubes and developmental outcomes at 9 to 11 years of age.
AB  - BACKGROUND: Developmental impairments in children have been attributed to
      persistent middle-ear effusion in their early years of life. Previously, we
      reported that among children younger than 3 years of age with persistent middle
      ear effusion, prompt as compared with delayed insertion of tympanostomy tubes did
      not result in improved cognitive, language, speech, or psychosocial development
      at 3, 4, or 6 years of age. However, other important components of development
      could not be assessed until the children were older. METHODS: We enrolled 6350
      infants soon after birth and evaluated them regularly for middle-ear effusion.
      Before 3 years of age, 429 children with persistent effusion were randomly
      assigned to undergo the insertion of tympanostomy tubes either promptly or up to
      9 months later if effusion persisted. We assessed literacy, attention, social
      skills, and academic achievement in 391 of these children at 9 to 11 years of
      age. RESULTS: Mean (+/-SD) scores on 48 developmental measures in the group of
      children who were assigned to undergo early insertion of tympanostomy tubes did
      not differ significantly from the scores in the group that was assigned to
      undergo delayed insertion. These measures included the Passage Comprehension
      subtest of the Woodcock Reading Mastery Tests (mean score, 98+/-12 in the early
      treatment group and 99+/-12 in the delayed-treatment group); the Spelling,
      Writing Samples, and Calculation subtests of the Woodcock-Johnson III Tests of
      Achievement (96+/-13 and 97+/-16; 104+/-14 and 105+/-15; and 99+/-13 and 99+/-13,
      respectively); and inattention ratings on visual and auditory continuous
      performance tests. CONCLUSIONS: In otherwise healthy young children who have
      persistent middle-ear effusion, as defined in our study, prompt insertion of
      tympanostomy tubes does not improve developmental outcomes up to 9 to 11 years of
      age. (ClinicalTrials.gov number, NCT00365092 [ClinicalTrials.gov].).

PMID- 17229953
TI  - International aeromedical evacuation.

PMID- 17229954
TI  - Parturition.

PMID- 17229955
TI  - Images in clinical medicine. Livedo reticularis and cold agglutinins.

PMID- 17229956
TI  - Case records of the Massachusetts General Hospital. Case 2-2007. A 49-year-old
      woman with a pigmented lesion on the arm.

PMID- 17229957
TI  - Sorting out breast-cancer gene signatures.

PMID- 17229958
TI  - The mammogram that cried Wolfe.

PMID- 17229959
TI  - The end of an era in otitis research.

PMID- 17229960
TI  - Wound healing with electric potential.

PMID- 17229961
TI  - Endarterectomy versus stenting for carotid stenosis.

PMID- 17229962
TI  - AMG 531 for chronic ITP.

PMID- 17229963
TI  - Radiotherapy for prostate cancer.

PMID- 17229964
TI  - Reversal of type 1 diabetes in mice.

PMID- 17229965
TI  - Lost in transcription.

PMID- 17229966
TI  - Amantadine-resistant influenza A (H3N2) virus in Japan, 2005-2006.

PMID- 17229967
TI  - The failure of torcetrapib: was it the molecule or the mechanism?

PMID- 17229968
TI  - Emerging thrombotic effects of drug eluting stents.

PMID- 17229969
TI  - CXCR4, a key modulator of vascular progenitor cells.

PMID- 17229970
TI  - Monocyte cAMP content is decreased in patients with stable angina.

PMID- 17229971
TI  - Evolution of cognitive function via redeployment of brain areas.
AB  - The creative reuse of existing neural components may have played a significant
      role in the evolutionary development of cognition. There are obvious evolutionary
      advantages to such redeployment, and the data presented here confirm three
      important empirical predictions of this account of the development of cognition:
      1) A typical brain area will be used by many cognitive functions in diverse task
      categories, (2) evolutionarily older brain areas will be deployed in more
      cognitive functions, and (3) more recent cognitive functions will use more, and
      more widely scattered, brain areas. These findings have implications not just for
      our understanding of the evolutionary origins of cognitive function but also for
      the practice of both clinical and experimental neuroscience.

PMID- 17229972
TI  - How humans reach: distinct cortical systems for central and peripheral vision.
AB  - Lesions of the posterior parietal cortex in humans can produce a specific
      disruption of visually guided hand movements termed optic ataxia. The fact that
      the deficit mainly occurs in peripheral vision suggests that reaching in foveal
      and extrafoveal vision relies on two different anatomical substrates. Using fMRI
      in healthy subjects, the authors demonstrated the existence of two systems,
      differently modulated by the two reaching conditions. Reaching in central vision
      involves a restricted network, including the medial intraparietal sulcus (mIPS)
      and the caudal part of the dorsal premotor cortex (PMd). Reaching in peripheral
      vision engages a more extensive network, including the parieto-occipital junction
      (POJ). Interestingly, POJ corresponds to the site of the lesion overlap that the
      authors recently found to be responsible for optic ataxia. These two sets of
      results converge to show that there is not a unique cortical network for reaching
      control but instead two systems engaged in reaching to targets in the central and
      peripheral visual field.

PMID- 17229973
TI  - NMDA Receptors in glia.
AB  - The amino acid L-Glutamate acts as the most ubiquitous mediator of excitatory
      synaptic transmission in the central nervous system. Glutamatergic transmission
      is central for diverse brain functions, being particularly important for
      learning, memory, and cognition. In brain pathology, excessive release of
      glutamate triggers excitotoxic neural cell death through necrotic or apoptotic
      pathways. Glutamate effects are mediated by several classes of glutamate
      receptors, expressed in virtually all cells of neural origin. Specifically
      important for both physiological information processing and cell damage are
      glutamate receptors of NMDA (N-methyl-D-aspartate) type, which, for a long time,
      were considered to be expressed exclusively in neurons. Recent studies have found
      functional NMDA receptors in brain macroglia, in astrocytes, and
      oligodendrocytes. Glial and neuronal NMDA receptors are functionally and
      structurally different; the glial receptors are weakly (if at all) sensitive to
      the extracellular magnesium block, which may indicate a predominant expression of
      the NR3 receptor subunit. In the cortex, astroglial NMDA receptors are activated
      upon physiological synaptic transmission. The physiological relevance of NMDA
      receptors in the white matter remains unknown; their activation upon ischemia
      triggers Ca(2+)-dependent damage of oligodendrocytes and myelin. The discovery of
      glial NMDA receptors further indicates the complex nature of intercellular
      signaling mechanisms in the brain, which involve all types of neural cells,
      connected through diverse types of chemical and electrical synapses.

PMID- 17229974
TI  - Magnetic resonance imaging of Alzheimer's pathology in the brains of living
      transgenic mice: a new tool in Alzheimer's disease research.
AB  - Alzheimer's disease (AD) is the most common cause of dementia in the elderly.
      Cardinal pathologic features of AD are amyloid plaques and neurofibrillary
      tangles, and most in the field believe that the initiating events ultimately
      leading to clinical AD center on disordered metabolism of amyloid beta protein.
      Mouse models of AD have been created by inserting one or more human mutations
      associated with disordered amyloid metabolism and that cause early onset familial
      AD into the mouse genome. Human-like amyloid plaque formation increases
      dramatically with age in these transgenic mice. Amyloid reduction in humans is a
      major therapeutic objective, and AD transgenic mice allow controlled study of
      this biology. Recent work has shown that amyloid plaques as small as 35 microm
      can be detected using in vivo magnetic resonance microimaging (MRMI) at high
      magnetic field (9.4 T). In addition, age-dependent changes in metabolite
      concentration analogous to those that have been identified in human AD patients
      can be detected in these transgenic mice using single-voxel (1)H magnetic
      resonance spectroscopy ((1)H MRS) at high magnetic field. These MR-based
      techniques provide a new set of tools to the scientific community engaged in
      studying the biology of AD in transgenic models of the disease. For example, an
      obvious application is evaluating therapeutic modification of disease
      progression. Toward the end of this review, the authors include results from a
      pilot study demonstrating feasibility of using MRMI to detect therapeutic
      modification of plaque progression in AD transgenic mice.

PMID- 17229975
TI  - Development of cortical maps: perspectives from the barrel cortex.
AB  - One approach to examining how higher sensory, motor, and cognitive faculties
      emerge in the neocortex is to elucidate the underlying wiring principles of the
      brain during development. The mammalian neocortex is a layered structure
      generated from a sheet of proliferating ventricular cells that progressively
      divide to form specific functional areas, such as the primary somatosensory (S1)
      and motor (M1) cortices. The basic wiring pattern in each of these functional
      areas is based on a similar framework, but is distinct in detail. Functional
      specialization in each area derives from a combination of molecular cues within
      the cortex and neuronal activity-dependent cues provided by innervating axons
      from the thalamus. One salient feature of neocortical development is the
      establishment of topographic maps in which neighboring neurons receive input
      relayed from neighboring sensory afferents. Barrels, which are prominent sensory
      units in the somatosensory cortex of rodents, have been examined in detail, and
      data suggest that the initial, gross formation of the barrel map relies on
      molecular cues, but the refinement of this topography depends on neuronal
      activity. Several excellent reviews have been published on the patterning and
      plasticity of the barrel cortex and the precise targeting of ventrobasal thalamic
      axons. In this review, the authors will focus on the formation and functional
      maturation of synapses between thalamocortical axons and cortical neurons, an
      event that coincides with the formation of the barrel map. They will briefly
      review cortical patterning and the initial targeting of thalamic axons, with an
      emphasis on recent findings. The rest of the review will be devoted to
      summarizing their understanding of the cellular and molecular mechanisms
      underlying thalamocortical synapse maturation and its role in barrel map
      formation.

PMID- 17229976
TI  - Polydendrocytes: NG2 cells with many roles in development and repair of the CNS.
AB  - NG2 cells, or polydendrocytes, are defined as glial cells that express the NG2
      proteoglycan and represent a fourth major glial cell population in the mammalian
      central nervous system. They are morphologically, antigenically, and functionally
      distinct from mature astrocytes, oligodendrocytes, and microglia. Although they
      are most often equated with oligodendrocyte progenitor cells, they exhibit some
      properties that are not commonly associated with those of progenitor cells that
      generate myelinating cells. This review discusses recent observations and
      unanswered issues related to their lineage and their role in remyelination,
      neural signaling, and axonal growth.

PMID- 17229977
TI  - Estrogens and epilepsy: why are we so excited?
AB  - Estrogens are essential for normal brain function throughout life. The source of
      estrogens is not only from the periphery, but local production has also been
      demonstrated in the CNS. Actions of estrogens involve a variety of effects, which
      include modulation of gene expression, regulation of neurotransmitter release, or
      direct inter-actions with neurotransmitter receptors. By these effects, estrogens
      affect neuronal excitability and thus may play an important role in seizure
      disorders. Although the original clinical as well as animal studies suggest that
      estrogens have exclusively proconvulsant properties, it has now become clear that
      estrogens also produce anticonvulsant effects. These opposite effects of
      estrogens on seizures may depend on treatment duration, latency prior to seizure
      testing, mode of administration, estrogen dose and hormonal status, estrogenic
      species, the region/neurotransmitter system involved, seizure type/model used,
      and sex. Animal data also suggest that estrogens, specifically beta-estradiol,
      have neuroprotective effects on seizure-induced hippocampal damage. Further
      studies are necessary to understand the role of estrogens in seizure disorders.
      Such under-standing is important, especially for women with epilepsy, to make
      qualified decisions regarding administration of contraceptives and hormonal
      replacement therapy as well as for the design of new therapeutic strategies for
      better seizure control and prevention of seizure-induced neuronal damage.

PMID- 17229978
TI  - Adipocytokines - novel link between inflammation and vascular function?
AB  - Obesity and obesity related diseases are a major public health problem. Recent
      studies have shown that fat tissue is not a simple energy storage organ, but
      exerts important endocrine and immune functions. These are achieved predominantly
      through release of adipocytokines, which include several novel and highly active
      molecules released abundantly by adipocytes like leptin, resistin, adiponectin or
      visfatin, as well as some more classical cytokines released possibly by
      inflammatory cells infiltrating fat, like TNF-alpha, IL-6, MCP-1 (CCL-2), IL-1.
      All of those molecules may act on immune cells leading to local and generalized
      inflammation and may also affect vascular (endothelial) function by modulating
      vascular nitric oxide and superoxide release and mediating obesity related
      vascular disorders (including hypertension, diabetes, atherosclerosis, and
      insulin resistance) but also cancer or non-alcoholic fatty liver diseases.
      Present review, in a concise form, focuses on the effects of major
      adipocytokines, characteristic for adipose tissue like leptin, adiponectin,
      resistin and visfatin on the immune system, particularly innate and adaptive
      immunity as well as on blood vessels. Macrophages and T cells are populating
      adipose tissue which develops into almost an organized immune organ. Activated T
      cells further migrate to blood vessels, kidney, brain and other organs surrounded
      by infiltrated fat leading to their damage, thus providing a link between
      metabolic syndrome, inflammation and cardiovascular and other associated
      disorders. Ceretain treatments may lead to significant changes in adipocytokine
      levels. For example include beta-2 adrenoreceptor agonists, thiazolidinediones as
      well as androgens lead to decrease of plasma leptin levels. Moreover future
      treatments of metabolic system associated disorders should focus on the
      regulation of adipocytokines and their modes of action.

PMID- 17229979
TI  - The physiological significance of the alternative pathways of angiotensin II
      production.
AB  - Although the use of angiotensin converting enzyme inhibitors (ACE-Is) in clinical
      practice brought the great chance to recognize the RAS role in the physiology and
      pathology, there are still many questions which we cannot answer. This article
      reviews actually known pathways of angiotensin II (Ang II) and other peptides of
      renin-angiotensin system (RAS) production and their physiological significance.
      The various carboxy- and aminopeptidases generate a range of peptides, like Ang
      II, Ang III, Ang IV, Ang-(1-7) and Ang-(1-9) possessing their own and known
      biological activity. In this issue especially the alternative pathways of Ang II
      synthesis involving enzymes other than angiotensin-converting enzyme (ACE) are
      discussed. We present many evidences for the significance of a new pathway of Ang
      II production. It has been clearly shown that Ang I may be converted to Ang-(1-9)
      by angiotensin-converting enzyme-related carboxypeptidase (ACE-2) and then into
      Ang II in some tissues, but the enzymes responsible for this process are unknown
      till now. Although there are many data proving the existence of alternative
      pathways of Ang II production, we can still block only ACE and angiotensin
      receptor 1 (AT(1)) in clinical practice. It seems that a lot needs to be done
      before we can wildly complexively control RAS and treat more effectively
      cardiovascular disorders such as hypertension or heart failure.

PMID- 17229980
TI  - Antioxidant treatment prevents cardiac protein oxidation after ischemia
      reperfusion and improves myocardial function and coronary perfusion in senescent
      hearts.
AB  - Cardiovascular ageing is associated with an increase in cardiac susceptibility to
      ischaemia and reperfusion and production of reactive oxygen species has been
      suspected to be responsible for this age-associated particular vulnerability. To
      determine whether administration of antioxidant treatment could afford some
      protection against ischaemia and reperfusion during aging, isolated perfused
      hearts from adult and senescent rats were submitted to normoxia (180 min),
      prolonged low-flow ischaemia (15% of initial coronary flow;180 min) or low-flow
      ischaemia/reperfusion (45 min/30 min), without or with antioxidant enzymes
      (superoxide dismutase+catalase; 50IU/ml). Contractile function and coronary
      perfusion were measured and protein oxidation was quantitated in left ventricle
      after normoxia, ischaemia and ischaemia/reperfusion. Protein oxidation was higher
      in senescent than in adult hearts after ischaemia-reperfusion, in contrast to
      prolonged ischaemia. During prolonged ischaemia, antioxidant treatment prevented
      coronary vasoconstriction at both ages and delayed contractile dysfunction in
      senescent hearts but did not limit protein oxidation. During reperfusion,
      antioxidant treatment prevented coronary vasoconstriction and protein oxidation
      at both ages and considerably improved recovery of contractile function in
      senescent hearts. In conclusion, antioxidant treatment fully protects the
      senescent heart against ischaemia/reperfusion but not against prolonged ischaemia
      injury, indicating that oxidative stress plays a central role in the age
      associated vulnerability to ischaemia-reperfusion.

PMID- 17229981
TI  - Ischemic preconditioning prevents endothelial dysfunction, P-selectin expression,
      and neutrophil adhesion by preventing endothelin and O2- generation in the post
      ischemic guinea-pig heart.
AB  - Evidence indicates that ischemia/reperfusion (IR) results in endothelial
      dysfunction and neutrophil adhesion in the post-ischemic myocardium and that
      ischemic preconditioning (IPC), superoxide dismutase (SOD), and anti-endothelin-1
      (ET-1) interventions prevent these effects. We tested the hypothesis that ET-1
      induced superoxide (O(2)(-)) generation mediates endothelial injury and
      neutrophil accumulation in the IR heart, that IPC protects the endothelium and
      prevents the adhesion by attenuating post-ischemic ET-1, and thus O(2)(-),
      generation, and that the mitochondrial ATP-dependent potassium channel (mK(ATP))
      triggers the IPC-induced protection. Langendorff-perfused guinea-pig hearts were
      subjected either to 30 min ischemia/35 min reperfusion (IR) or were
      preconditioned prior to IR with three cycles of either 5 min ischemia/5 min
      reperfusion or 5 min infusion/5 min wash-out of mK(ATP) opener diazoxide (0.5
      microM). Neutrophils were infused to the hearts at 15-25 min of the reperfusion.
      Coronary flow responses to acetylcholine (ACh) and nitroprusside (SNP) served as
      measures of endothelium-dependent and -independent vascular function,
      respectively. Myocardial outflow of ET-1 and O(2)(-), P-selectin expression,
      neutrophil adhesion and functional recoveries were followed during reperfusion.
      IR augmented ET-1 and O(2)(-) outflow, P-selectin expression, and neutrophil
      adhesion, and impaired ACh response. These effects were attenuated or prevented
      by IPC and diazoxide, and 5-hydroxydecanoate (a selective mK(ATP) blocker)
      abolished the effects of IPC and diazoxide. SOD (150 U/ml) and tezosentan (5 nM,
      a mixed ET-1-receptor antagonist) mimicked the effects of IPC, although they had
      no effect on the ET-1 generation. The preventive effect of IPC, SOD and
      tezosentan on P-selectin expression preceded their effect on neutrophil adhesion.
      These data suggest that in guinea-pig heart: (i) ET-1-induced O(2)(-) generation
      mediates the post-ischemic endothelial dysfunction, P-selectin expression and
      neutrophil adhesion; (ii) IPC and diazoxide afford protection by attenuating the
      ET-1, and thus O(2)(-) generation; (iii) the mK(ATP) opening triggers the IPC
      protection; (iv) endothelial injury promotes post-ischemic neutrophil adhesion,
      but not vice versa.

PMID- 17229982
TI  - Effect of prolonged dynamic exercise on plasma adrenomedullin concentration in
      healthy young men.
AB  - The aim of the study was to find out whether prolonged exercise influences plasma
      adrenomedullin (ADM) concentration and whether it is related to the hormonal,
      metabolic and cardiovascular changes. Eighteen healthy subjects (age 25+/-1 yrs)
      were submitted to cycle exercise for 90 min at 70% of maximal oxygen uptake.
      Heart rate (HR) and blood pressure (BP) were measured continously. Before, at
      30(th) min, and at the end of exercise venous blood samples were taken for [ADM],
      noradrenaline [NA], adrenaline [A], atrial natriuretic peptide [ANP], plasma
      renin activity PRA, interleukin-6 [IL-6] and lactate [LA] determination.
      Significant increases in plasma ADM and IL-6 were found at 90(th) min whereas
      other hormones were elevated already at 30(th) min of exercise. Positive
      correlations were ascertained between [ADM] and [NA] (r=0.47), [ANP] (r=0.35) or
      [IL-6] (r=0.35) and between exercise-induced increases in [ADM] and [NA]
      (r=0.38). PRA correlated positively with [NA] and [ANP]. Negative correlation was
      found between plasma [ADM] and diastolic BP. The present data suggest that
      increase in sympathetic nervous activity and cytokine induction during prolonged
      exercise may be involved in plasma ADM release and that increase in ADM and ANP
      secretion may be a compensatory mechanism against further elevation of blood
      pressure.

PMID- 17229983
TI  - Effect of ketanserin and amphetamine on nigrostriatal neurotransmission and
      reactive oxygen species in Parkinsonian rats. In vivo microdialysis study.
AB  - 5-HT(2A/2C) receptors are one of the most important in controlling basal ganglia
      outputs. In rodent models of Parkinson's disease (PD) blockade of these receptors
      increases locomotion and enhances the actions of dopamine (DA) replacement
      therapy. Moreover, previously we established that 5-HT(2A/2C) antagonist
      attenuate DA D(1) agonist mediated vacuous chewing movements (VCMs) which are
      considered as an animal representation of human dyskinesia. These findings
      implicate 5-HT neuronal phenotypes in basal ganglia pathology, and promote 5
      HT(2) antagonists as a rational treatment approach for dyskinesia that is
      prominent in most instances of PD replacement therapy. In the current study we
      determined whether ketanserin (KET) and/or amphetamine (AMPH) affected
      dopaminergic neurotranssmision in intact and fully DA-denervated rats. Moreover,
      we looked into extraneuronal content of HO. of the neostriatum after AMPH and/or
      KET injection, assessed by HPLC analysis of dihydroxybenzoic acids (2,3- and 2, 5
      DHBA) - spin trap products of salicylate. Findings from the present study
      demonstrated that there are no substantial differences in extraneuronal HO.
      generation in the neostriatum between control and parkinsonian rats. KET did not
      affect DA release in the fully DA-denervated rat's neostriatum and also did not
      enhance HO. production. As 5-HT(2A/2C) receptor-mediated transmission might prove
      usefulness not only in addressing motor complications of PD patients (dyskinesia)
      but also in addressing non-motor problems such depression and/or L-DOPA evoked
      psychosis, the findings from the current study showed that the use of 5-HT(2A/2C)
      receptor antagonists in Parkinson's disease does not impend the neostriatal
      neuropil to be damaged by these drugs. We concluded that 5-HT(2A/2C) receptor
      antagonists may provide an attractive non-dopaminergic target for improving
      therapies for some basal ganglia disorders.

PMID- 17229984
TI  - Regulation of cGMP synthesis in cultured podocytes by vasoactive hormones.
AB  - The podocytes are highly differentiated cells playing a key role in glomerular
      filtration. Vasoactive factors including angiotensin II (Ang II) and cyclic
      guanosine 5' monophosphate (cGMP) are synthesized by these cells upon stimulation
      as well as in the basal state. In this study we have tested whether angiotensin
      II affects the total synthesis of cGMP in primary culture of rat podocytes. The
      cells were stimulated with atrial natriuretic peptide (ANP) and/or a nitric oxide
      (NO) donor, S-nitroso-N-acetyl penicillamine (SNAP), in the absence or presence
      of Ang II. The cGMP synthesis was determined by radioimmunoassay (RIA). ANP or
      SNAP alone increased the cGMP synthesis in podocytes although the effects were
      not additive unless Ang II was present in the medium. Ang II suppressed the ANP
      dependent cGMP synthesis whereas SNAP-dependent cGMP production remained
      unaffected. These effects were prevented by a non-specific antagonist of Ang II
      receptors (AT), saralasin. Adversely, PD123319, a specific inhibitor of AT2
      receptors, augmented inhibition of ANP-dependent and enhanced the NO-dependent
      cGMP production. Probenecid, an inhibitor of cGMP extrusion from the cells,
      suppressed the cGMP generation by both ANP and SNAP. We conclude that cGMP
      synthesis in cultured podocytes is modulated by angiotensin II and that two
      adversely acting receptors, AT1 and AT2 are involved in this effect.
      Additionally, production of cGMP might be intrinsically inhibited by cGMP
      accumulating inside the cells.

PMID- 17229985
TI  - Effects of novel plant antioxidants on platelet superoxide production and
      aggregation in atherosclerosis.
AB  - Superoxide anion is produced in human platelets predominantly by Nox2-dependent
      NADPH oxidases. In vitro experiments have shown that it might play a role in
      modulating platelet functions. The relationship between platelet superoxide
      production and aggregation remains poorly defined. Accordingly, we aimed to study
      superoxide production and aggregation in platelets from subjects with significant
      cardiovascular risk factors (hypertension, hypercholesterolemia, smoking and
      diabetes mellitus) and from control individuals. Moreover, we studied the effects
      of novel polyphenol-rich extracts of Aronia melanocarpa (chokeberry) berries on
      platelet function in vitro. Superoxide production was significantly increased in
      patients with cardiovascular risk profile when compared to controls, while
      platelet aggregation in response to either collagen or thrombin were borderline
      higher, and did not reach statistical significance. Interestingly, no
      relationship was observed between platelet aggregation ex vivo and platelet
      superoxide production in either of studied groups. No correlation was found
      between endothelial function (measured by FMD) and platelet aggregation ex vivo
      either. Polyphenol-rich extracts of A. melanocarpa berries caused a significant
      concentration dependent decrease in superoxide production only in patients with
      cardiovascular risk factors, while no effect was observed in the control group.
      A. melanocarpa extracts abolished the difference in superoxide production between
      risk factor patients and controls. A. melanocarpa extracts exerted significant
      concentration dependent anti-aggregatory effects in both studied groups, which
      indicated that these effects may be independent of it's ability to modulate
      superoxide production. The anti-aggregatory effects of chokeberry extracts were
      similar irrespective of aggregation inducing agent (collagen or thrombin).
      Moreover, they appear to be independent of platelet NO release as NOS inhibition
      by L-NAME did not lead to their abrogation.

PMID- 17229986
TI  - Oxytocin release after bleeding in rat: the role of sympathetic and renin
      angiotensin system.
AB  - The aim of this experiment was to compare the role of renin-angiotensin and
      sympathetic nervous system in post-haemorrhagic mechanism of oxytocin release.
      Oxytocin content in venous dialysates was determined by radioimmunoassay. In
      control rats the release of oxytocin into dialysates did not change during whole
      experiment. The injection of captopril induced 2-fold higher oxytocin release,
      but caused no change in oxytocin release after bleeding. Superior cervical
      ganglionectomy (SCGx) 20 days before, caused 5-fold higher increase in oxytocin
      release than in control group. Injection of captopril in rats after SCGx, did not
      decrease the high level of oxytocin in dialysate. However, bleeding increased
      oxytocin release and 1 hour after bleeding the highest - 14-fold increase, took
      place. In the contrary to 14-fold increase in oxytocin release in animals with
      superior cervical ganglia (SCG), bleeding after SCGx caused only 2-fold higher
      oxytocin release. When SCGx, bleeding and injection of captopril were done
      simultaneously, oxytocin release remained on the control concentration level. We
      assumed that blockade of renin angiotensin system and sympathetic dennervation
      prevent the increase in oxytocin release after bleeding. On basis of our present
      experiments, it can be assumed that, in posthaemorrhagic oxytocin release into
      the blood, sympathetic innervation derived from SCGx, as well as, renin
      angiotensin system are involved.

PMID- 17229987
TI  - Leptin effect on nitric oxide and GnRH-induced FSH secretion from ovine pituitary
      cells in vitro.
AB  - The secretion of gonadotrophins from anterior pituitary cells can be modulated by
      leptin and signals originating from the immune system, among others, by nitric
      oxide (NO). There are some studies that have demonstrated a role for leptin and
      NO in the regulation of FSH in rodents, however, no similar data are available in
      regards to ewes. Therefore, the objective of the present study was to analyse the
      leptin effect on GnRH-induced FSH secretion from the ovine anterior pituitary
      cells in vitro. Additionally, the influence of leptin on NO release and its role
      in the GnRH and leptin-modulated secretion of FSH from pituitary gland of ewes
      was investigated. The obtained results show that the influence of leptin on FSH
      secretion is biphasic. Leptin in concentration 10(-8) and 10(-7) M/l
      significantly enhances, whereas 10(-6) and 10(-5) M/l of leptin suppresses FSH
      secretion from the pituitary cells in comparison to the control. The secretion of
      FSH and NO release under the influence of leptin are in very high positive
      correlation (r=0.77). The inhibition of NO synthesis with L-NAME., instead,
      disables leptin from the stimulation of FSH secretion.

PMID- 17229988
TI  - Production of prostacyclin and prostaglandin E2 in resting and IL-1beta
      stimulated A549, HUVEC and hybrid EA.HY 926 cells.
AB  - Production of arachidonic acid (AA) metabolites - prostacyclin (PGI(2)) in large
      vessels and prostaglandin E(2) (PGE(2)) in microcirculation is intrinsically
      involved in maintenance of vascular wall homeostasis. EA.hy 926 is a hybrid cell
      line, is derived by fusion of HUVEC with A549 cells. The aim of this study was to
      examine the production of prostacyclin and PGE2 in resting and IL-1beta
      stimulated EA.ha 926 cells, in comparison with its progenitor cells. Non
      stimulated EA.hy 926 cells has been found to produce much lower amounts of
      prostacyclin than resting HUVEC. Resting hybrid cells produced more PGE(2) than
      prostacyclin, despite they expressed high levels of COX-1 and PGI(2) synthase. On
      the contrary to HUVEC and A549, EA.hy 926 cells did not respond to IL-1beta with
      COX-2 induction and increase of prostaglandin production, however they did it in
      response to lysophosphatidylcholine (LPC). The characteristics of EA.hy 926 cells
      in terms of the pattern of prostanoid formation could facilitate studies on
      endothelial metabolism and role of these important lipid mediators.

PMID- 17229989
TI  - Involvement of cyclooxygenase-1, prostaglandin E2 and EP1 receptors in acid
      induced HCO3- secretion in stomach.
AB  - We investigated the cyclooxygenase (COX) isoforms as well as prostaglandin E
      receptor EP subtypes responsible for acid-induced gastric HCO(3)(-) secretion in
      rats and EP receptor-knockout (-/-) mice. Under urethane anesthesia, a chambered
      stomach (in the presence of omeprazole) was perfused with saline, and HCO(3)(-)
      secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl.
      Mucosal acidification was achieved by exposing the stomach for 10 min to 50 or
      100 mM HCl. Acidification of the mucosa increased the secretion of HCO(3)(-) in
      the stomach of both rats and WT mice, in an indomethacin-inhibitable manner. The
      acid-induced gastric HCO(3)(-) secretion was inhibited by prior administration of
      indomethacin and SC-560 but not rofecoxib in rats and mice. Acidification
      increased the PGE(2) content of the rat stomach, and this response was
      significantly attenuated by indomethacin and SC-560 but not rofecoxib. This
      response was also attenuated by ONO-8711 (EP1 antagonist) but not AE3-208 (EP4
      antagonist) in rats and disappeared in EP1 (-/-) but not EP3 (-/-) mice. PGE(2)
      increased gastric HCO(3)(-) secretion in both rats and WT mice, and this action
      was inhibited by ONO-8711 and disappeared in EP1 (-/-) but not EP3 (-/-) mice.
      These results support a mediator role for endogenous PGs in the gastric response
      induced by mucosal acidification and clearly indicate that the enzyme responsible
      for production of PGs in this process is COX-1. They further show that the
      presence of EP1 receptors is essential for the increase in the secretion of
      HCO(3)(-) in response to mucosal acidification in the stomach.

PMID- 17229990
TI  - Pancreatic secretion differs according to the genotype of growing pigs.
AB  - The objective of this study was to investigate the secretion of pancreatic
      enzymes and antibacterial activity in weaned pigs of three pure breeds, Pietrain,
      Duroc and Polish synthetic line 990, to look for eventual differences related to
      the genotype. Six male pigs of each breed, about 24 kg mean body weight, were
      equipped with chronic pancreatic duct catheters and duodenal cannulas to assess
      pure pancreatic juice, and jugular vein catheters for blood withdrawal.
      Pancreatic juice was collected before and after the morning feeding. Protein
      output and enzyme activities revealed two distinct profiles: strong manifestation
      of the prandial phase in Pietrain and line 990 pigs, and weak manifestation in
      Duroc. The antibacterial activity did not follow the enzyme kinetics, and it was
      the strongest in pancreatic juice from Pietrain pigs. Postprandial insulinaemia
      was reduced in the order of: line 990>Pietrain>Duroc. A slight (not significant)
      tendency towards a reduction of leptin after feeding in synthetic line 990
      corresponded with elevated secretion of pancreatic enzymes and plasma insulin.
      The presented results suggest that the prandial secretion of pancreatic juice
      differs according to genotype, and the differences may be in part related to
      release of insulin.

PMID- 17229991
TI  - The ghrelin pentapeptide inhibits the secretion of pancreatic juice in rats.
AB  - Ghrelin, a 28 amino acids polypeptide was recognized as an endogenous ligand for
      the growth hormone secretagogue receptor. It turned out that the entire sequence
      of ghrelin is not necessary for performing the above-mentioned functions. It was
      suggested that 5 residues (Gly-Ser-Ser(n-octanoyl)-Phe, pentaghrelin) constituted
      functionally active part of the full-length polypeptide. Ghrelin-28 was found to
      inhibit pancreatic enzyme output in rats, though the effect of pentaghrelin was
      not studied so far. The study aimed to determine the involvement of pentaghrelin
      in pancreatic juice secretion in anaesthetized rats. Male Wistar rats (220 +/- 20
      g body weight, b. wt.) were anesthetized, the external jugular vein and common
      biliary-pancreatic duct were cannulated. Pentaghrelin boluses (i.v., 1.2, 12, and
      50 nmol kg(-1) b. wt.) were injected every 30 min with or without CCK-8 infusion,
      duodenal mucosal CCK(1) receptor blockade with tarazepide, vagotomy and capsaicin
      pretreatment. Pentaghrelin boluses reduced the volume of pancreatic-biliary
      juice, protein and trypsin outputs both under basal and CCK-8-stimulated
      conditions in a dose-dependent manner. However, exogenous pentaghrelin failed to
      affect the pancreatic secretion in rats subjected to vagotomy, capsaicin
      deactivation of afferents or pretreatment with Tarazepide. In conclusion,
      pentaghrelin may control exocrine pancreas secretion by affecting duodenal
      neurohormonal mechanism(s) involving CCK and vagal nerves in rats.

PMID- 17229992
TI  - Substitution F659G in the Irr1p/Scc3p cohesin influences the cell wall of
      Saccharomyces cerevisiae.
AB  - The sister chromatid cohesion complex of Saccharomyces cerevisiae is composed of
      proteins termed cohesins. The complex forms a ring structure that entraps sister
      DNAs, probably following replication. The mechanism of cohesion is universal and
      the proteins participating in this process are evolutionarily highly conserved.
      We investigated the Irr1p/Scc3p cohesin subunit, an under-studied protein. We
      show that the presence of a mutated copy of IRR1 gene, encoding the F658G
      substitution in Irr1p, changes the sensitivity of the heterozygous irr1-1/IRR1
      diploid to cell wall-affecting compounds. Microscopic images indicate that chitin
      distribution in the mutant cell wall is affected, although the biochemical
      composition of the cell wall is not drastically changed. This observation
      suggests that irr1-1 mutation in heterozygous state may influence the cell wall
      integrity and indicates a possible link between mechanisms regulating the cell
      wall biosynthesis, nuclear migration and chromosome segregation.

PMID- 17229993
TI  - Intravenously administered vasodilatory prostaglandins increase retinal and
      choroidal blood flow in rats.
AB  - We established an experimental system for measuring blood flow in the rat fundus
      and examined whether intravenously administered vasodilatory prostaglandins
      (PGE(1), PGE(2), and PGI(2)), 8-(4-chlorophenylthio)-cAMP (a cAMP analogue), and
      nicardipine (a Ca(2+)-channel blocker) increase fundus blood flow (FBF). Under
      artificial ventilation, rats were injected with tetrodotoxin (50 microg/kg, i.v.)
      to eliminate any nerve activity and prevent movement of the eye. After
      tetrodotoxin, the rats were infused with norepinephrine (0.3 - 0.5 microg . kg(
      1) . min(-1)) and epinephrine (2.7 - 4.5 microg . kg(-1) . min(-1))
      simultaneously to maintain adequate systemic circulation. We found that
      intravenous infusion of PGE(1) (2 - 10 microg . kg(-1) . min(-1)), PGE(2) (3 - 30
      microg . kg(-1) . min(-1)), and PGI(2) (1 - 10 microg . kg(-1) . min(-1))
      increased the FBF in a dose-dependent manner. The vasodilatory PGs decreased
      arterial pressure, whereas they did not affect heart rate. Like vasodilatory PGs,
      8-(4-chlorophenylthio)-cAMP (30 micromol/kg, i.v.) increased FBF and decreased
      arterial pressure. While infusion of nicardipine (0.3 - 3 microg . kg(-1) . min(
      1)) produced comparable depressor responses with those to vasodilatory PGs and
      the cAMP analogue, it did not increase FBF. These results suggest that
      vasodilatory PGs and cAMP act more selectively than Ca(2+)-channel blockers on
      retinal/choroidal blood vessels. Therefore, the vasodilatory PGs might be
      considered to be possible candidates for the therapeutics to treat disorders of
      retinal/choroidal circulation.

PMID- 17229994
TI  - Differential expression of 3beta-hydroxysteroid dehydrogenase mRNA in rat testes
      exposed to endocrine disruptors.
AB  - Expression of 3beta-hydroxysteroid dehydrogenase (3beta-HSD) is mainly found in
      the Leydig cells from which steroid hormones are biosynthesized in the testes. To
      investigate whether endocrine disruptors affect the microenvironment of the
      testes, the mRNA expression of 3beta-HSD as a molecular marker for androgen
      biosynthesis was analyzed in rat testes exposed to several endocrine disruptors
      using a reverse transcription-polymerase chain reaction technique. Testosterone
      [50, 200 and 1,000 microg/kg body weight (BW)], flutamide (1, 5 and 25 mg/kg BW),
      ketoconazole (0.2, 1, 5 and 25 mg/kg BW), diethylhexyl phthalate (10, 50 and 250
      mg/kg BW), nonylphenol (10, 50, 100 and 250 mg/kg BW), octylphenol (10, 50 and
      250 mg/kg BW), and diethylstilbestrol (10, 20 and 40 microg/kg BW) were orally
      administered to 4-week-old Sprague-Dawley rats for 3 weeks daily. Although
      testosterone at a low dose (50 microg/kg/day) increased the expression of 3beta
      HSD mRNA, it was significantly decreased in the rats treated with 200 or 1,000
      microg/kg/day testosterone compared with the control group (P<0.05). Furthermore,
      ketoconazole, diethylhexyl phthalate, nonylphenol, octylphenol and
      diethylstilbestrol caused significant downregulation of 3beta-HSD mRNA in the
      testes at all doses (P<0.05). However, flutamide remarkably increased the level
      of 3beta-HSD mRNA in the testes (P<0.05). These results suggest that endocrine
      disruptors may influence androgen biosynthesis in the testes by alteration of
      3beta-HSD mRNA expression.

PMID- 17229995
TI  - Effects of storage and passage of bovine luteal endothelial cells on endothelin-1
      and prostaglandin F2alpha production.
AB  - To establish a storage system for isolated bovine luteal endothelial cells
      (LECs), we investigated the basal and tumor necrosis factor (TNF) alpha
      stimulated production of endothelin-1 (ET-1) and prostaglandin (PG) F2alpha in
      unfrozen and frozen-thawed LECs until passage 10. LECs were obtained from
      developing corpora lutea (CL; days 5-7 of the estrous cycle) using enzymatic
      digestion and magnetic beads coated with lectin BS-1. The LECs were frozen at -80
      C or further cultured and/or passaged until passage 10 in DMEM/Ham's F-12
      supplemented with 10% calf serum. The hormonal productions of unfrozen and
      frozen/thawed LECs were compared through passages 2-10. When both the unfrozen
      and frozen/thawed cells reached confluence, the culture medium was replaced with
      fresh medium containing 0.1% bovine serum albumin (BSA), and the cells were
      incubated with TNFalpha (50 ng/ml) for 12 h. The basal productions of ET-1 and
      PGF2alpha by the unfrozen and frozen/thawed LECs were similar at passage 2. The
      basal production of PGF2alpha by LECs was not altered by passage and storage at 
      80 C, whereas the basal production of ET-1 decreased from passage 2 and 3 to
      passage 4 in the unfrozen LECs and from passage 2 to passage 3 in the
      frozen/thawed LECs. However, production of ET-1 by the unfrozen and frozen/thawed
      LECs was similar between passages 4-10 and passages 3-10, respectively. Exposure
      of LECs to TNFalpha increased (P<0.05) ET-1 and PGF2alpha production by the
      unfrozen and frozen-thawed LECs in all passages examined. Thus, LECs obtained
      from developing CLs and stored until passage 10 can be used for study of the
      physiology of LECs in vitro.

PMID- 17229996
TI  - Evaluation of the estrogenic activity of the wild Pueraria mirifica by vaginal
      cornification assay.
AB  - The aim of this study was to evaluate the estrogenic activity of tuberous samples
      of phytoestrogen-rich Pueraria mirifica collected from 25 of 76 provinces in
      Thailand by vaginal cornification assay. Tuberous powders were prepared and
      administered to ovariectomized rats for 14 consecutive days at dosages of 10, 100
      and 1,000 mg/kg BW respectively, and were compared with a daily treatment with 2
      mg/kg BW 17beta-estradiol (E(2)). Rats treated with 10 mg/kg BW Pueraria mirifica
      showed no vaginal cornification. Treatment with 100 mg/kg BW Pueraria mirifica
      from 13 out of 25 plant samples resulted in development of vaginal cornification.
      The cell count percentages of the vaginal smeared cells for the treatment with
      the 2 plant samples that exhibited the fastest vaginal cornification revealed
      large variation in their estrogenic activities. Treatment with 1,000 mg/kg BW
      Pueraria mirifica from all plant samples produced vaginal cornification with the
      mean value for the period (day) of first appearance of cornified cells being 4.08
      days compared to 2 days with 2 mg/kg BW E(2). The overall appearance period (day)
      of cornified cells during the treatment and post-treatment period with 1,000
      mg/kg BW per day Pueraria mirifica was shorter than treatment with 2 mg/kg BW
      E(2). The results demonstrate that the plant population shows differential
      estrogenic activity as evaluated by vaginal cornification assay.

PMID- 17229997
TI  - Oxidative stress induced lipocalin 2 gene expression: addressing its expression
      under the harmful conditions.
AB  - Lipocalin 2 (Lcn2, NGAL) is a member of the lipocalin superfamily with diverse
      functions such as the transport of fatty acids and the induction of apoptosis.
      Previous reports indicated that expression of Lcn2 is induced under harmful
      conditions. However, the mechanisms of the induction of Lcn2 expression remain to
      be elucidated. In this report, we intended to identify the factor or factors that
      induce Lcn2 expression. Up-regulation of Lcn2 expression after X-ray exposure was
      detected in the heart, the kidney and especially in the liver. Primary culture of
      liver component cells revealed that this up-regulation in the liver was induced
      in hepatocytes. Up-regulation of Lcn2 expression was also detected in HepG2 cells
      after the administration of X-rays or H(2)O(2). Interestingly, up-regulation of
      Lcn2 expression after H(2)O(2) treatment was canceled by the addition of the anti
      oxidants, dimethylsulfoxide or cysteamine. These results strongly suggest that
      Lcn2 expression is induced by reactive oxygen species. Therefore, Lcn2 could be a
      useful biomarker to identify oxidative stress both in vitro and in vivo.

PMID- 17229998
TI  - Split dose recovery studies using homologous recombination deficient gene
      knockout chicken B lymphocyte cells.
AB  - To understand the role of proteins involved in DSB repair modulating SLD
      recovery, chicken B lymphoma (DT 40) cell lines either proficient or deficient in
      RAD52, XRCC2, XRCC3, RAD51C and RAD51D were subjected to fractionated irradiation
      and their survival curves charted. Survival curves of both WT DT40 and RAD52 (-/
      ) cells had a big shoulder while all the other cells exhibited small shoulders.
      However, at the higher doses of radiation, RAD51C(-/-) cells displayed
      hypersensitivity comparable to the data obtained for the homologous recombination
      deficient RAD54(-/-) cells. Repair of SLD was measured as an increase in survival
      after a split dose irradiation with an interval of incubation between the
      radiation doses. All the cell lines (parental DT40 and genetic knockout cell
      lines viz., RAD52(-/-), XRCC2(-/-), XRCC3(-/-) RAD51C(-/-) and RAD51D(-/-)) used
      in this study demonstrated a typical split-dose recovery capacity with a specific
      peak, which varied depending on the cell type. The maximum survival of WT DT40
      and RAD52(-/-) was reached at about 1-2 hours after the first dose of radiation
      and then decreased to a minimum thereafter (5h). The increase in the survival
      peaked once again by about 8 hours. The survival trends observed in XRCC2 (-/-),
      XRCC3(-/-), RAD51C (-/-) and RAD51D(-/-) knockout cells were also similar, except
      for the difference in the initial delay of a peak survival for RAD51D(-/-) and
      lower survival ratios. The second phase of increase in the survival in these cell
      lines was much slower in XRCC2(-/-) , XRCC3(-/-), RAD51C(-/-) and RAD51D(-/-) and
      further delayed when compared with that of RAD52(-/-) and parental DT40 cells
      suggesting a dependence on their cell cycle kinetics. This study demonstrates
      that the participation of RAD52, XRCC2, XRCC3, RAD51C and RAD51D in the DSB
      repair via homologous recombination is of less importance in comparison to RAD54,
      as RAD54 deficient cells demonstrated complete absence of SLD recovery.

PMID- 17229999
TI  - [Research on measures for intractable pancreatic disease--current status and
      proposal to improve the outcome of intractable severe acute pancreatitis].

PMID- 17230000
TI  - [Role of bile acids on Barrett's esophagus].

PMID- 17230001
TI  - [Nitric oxide generated at gastro-oesophageal junction].

PMID- 17230002
TI  - [Case of submucosal esophageal carcinoma with multiple liver metastasis showing
      high serum levels of CEA and CA19-9].
AB  - A 57-year-old man was admitted because of abdominal fullness. An abdominal
      ultrasonographic study disclosed multiple space-occupying lesions (SOL) in the
      liver. On blood examinationC the serum levels of CEA and CA19-9 were
      significantly high while those of AFP and SCC were within normal ranges.
      Endoscopically biopsied specimens of the lower esophagus histologically revealed
      poorly differentiated squamous cell carcinoma. Pathohistologically similar
      findings were obtained from the needle biopsied specimen of the SOL in the liver.
      Thus the patient was diagnosed as having squamous cell carcinoma of the esophagus
      with liver metastasis. On the 41st hospital day the patient died and an autopsy
      was performed. Although multiple metastases were recognized, cancer cells were
      limited within the submucosa of the esophagus. Immunostaining of CEA and CA19-9
      was positive on the carcinoma cells both in the esophagus and the liver. Thus a
      relation between the biological malignancy of esophageal cancer and serum levels
      of CEA and CA19-9 was suggested.

PMID- 17230003
TI  - [Case of multiple (at least 28 lesions) gastric intramural metastases from
      gastric cancer].
AB  - A 76-year-old man was admitted for treatment of gastric cancer that causing
      anorexia. Endoscopy showed the stenosis in the antrum of the stomach and multiple
      small nodules with erosion from the upper body to the corpus of the stomach.
      Total gastrectomy with Roux-en-Y reconstruction was performed. On the resected
      specimen, there were at least 28 nodules with erosion in the submucosal layer of
      the entire stomach. The lesions had no continuity with one another and were the
      same histological type, poorly differentiated adenocarcinoma. We diagnosed these
      lesions as intramural metastases of gastric cancer.

PMID- 17230004
TI  - [Case of ulcerative colitis associated with drug-induced hypersensitivity
      syndrome (DIHS) by salazosulfapyridine].
AB  - We experienced a case of drug-induced hypersensitivity syndrome (DIHS) for
      salazosulfapyridine (SASP). After we started administration of SASP in a 26-year
      old man with ulcerative colitis (UC), he had symptoms resembling infectious
      mononucleosis, high fever, skin eruption, cervical lymphadenopathy, elevate white
      blood cell count with atypical lymphocyte, and liver dysfunction. We diagnosed
      the illness as drug-induced hypersensitivity syndrome (DIHS) due to SASP. We
      halted SASP and started administration of methylprednisolone and prednisolone but
      his condition deteriorated. We changed to administration of betamethasone and he
      recovered. In cases of DIHS accompanied by UC, we should administer drugs
      carefully and recognize serious complications.

PMID- 17230005
TI  - [Case of severe ulcerative colitis successfully treated with intravenous
      cyclosporine without high dose corticosteroid].
AB  - A 44-year-old women developed marked myopathy one year earlier, when she was
      treated with intravenous prednisolone for acute severe exacerbation of ulcerative
      colitis. When she was admitted to our hospital for another severe exacerbation,
      intravenous cyclosporine A was administered as monotherapy because she could not
      tolerate corticosteroid. The treatment was successful and she obtained complete
      remission. Cyclosporine A monotherapy is considered to be a valuable alternative
      to proctocolectomy for severe ulcerative colitis patients who cannot tolerate
      corticosteroid.

PMID- 17230006
TI  - [Case of solitary necrotic nodule of the liver difficult to distinguish from
      malignant hepatoma].
AB  - In a 72 years old woman, abdominal computed tomography (CT) disclosed
      multicentric hypervascular tumor in S4 of the liver, and it was T1.T2 by the MRI,
      and a high signal was presented together. Stenosis was shown by ERCP at the same
      site. Cholangiocellular carcinoma was suspected before operation, but malignant
      change was not recognized by frozen section, so the operation was finished.
      Later, a diagnosis of solitary necrotic nodule of the liver was established by
      pathological diagnosis. Solitary necrotic nodule of the liver is a benign tumor.

PMID- 17230007
TI  - [Case of acute hepatitis associated with Basedow's disease].
AB  - A 20-year-old woman given a diagnosis of hyperthyroidism (Basedow's disease) had
      been subsequently treated with methimazole since 1999. As she could not be made
      euthyroid, surgery was planned to relieve the symptoms. Because of liver
      dysfunction after discontinuation of methimazole and administration of iodine,
      she was admitted to the hospital. She was negative for hepatitis A, B and C virus
      serologies, but positive for anti-nuclear antibodies. A liver biopsy, which
      showed features of chronic active hepatitis, led to the diagnosis of autoimmune
      hepatitis (AIH). Interestingly, normalization of serum T4 correlated with
      improvement of serum aminotransferases. This leads us to speculate that this
      patient's liver dysfunction may have been AIH exacerbated by the liver
      dysfunction of hyperthyroidism rather than acute deterioration of AIH itself.

PMID- 17230008
TI  - [Case of primary malignant fibrous histiocytoma of the diaphragm discovered by
      liver function disorder].
AB  - We present the case of a 67-year-old man with primary malignant fibrous
      histiocytoma (MFH) of the diaphragm. He was admitted to our hospital with
      anorexia and loss of body weight. High serum levels of AST, ALT, ALP and gamma
      GTP were observed. Several imaging studies disclosed a large tumor on the right
      side of the diaphragm to the right lobe of the liver. The entire tumor was
      resected, and histopathological examination of the specimen revealed the
      characteristics of MFH. MFH originating from the diaphragm is very rare, and we
      present the case of this patient in addition to a discussion of previous
      literature.

PMID- 17230009
TI  - [Case report of asymptomatic arteriovenous malformation (AVM) of the pancreas;
      diagnostic advantage of three-dimensional computed tomography].
AB  - A 72-year-old man with diabetes mellitus and hypertension was admitted for
      further examination and therapy of diabetes. In order to evaluate his pancreas,
      abdominal computed tomography (CT) was performed, showing a space-occupying
      lesion (SOL) in the pancreatic uncus. He did not show any symptoms related to the
      pancreas or gastro intestinal tract. Three-dimensional CT (3D-CT) indicated that
      the SOL was not a solid tumor but a vessel fistula, fed by the superior
      mesenteric artery and the gastro duodenal artery, drained by the superior
      mesenteric vein. Abdominal angiography also showed its peculiar vessel structure,
      confirming arterio-venous (A-V) malformation in the pancreas. Pancreatic A-V
      malformation is a rare condition but should not be forgotten in the differential
      diagnosis of pancreatic SOL. Our case showed the advantages of 3D-CT with its low
      invasiveness and convenience for the diagnosis of A-V malformation in the
      pancreas.

PMID- 17230010
TI  - [Lesions in the gastroesophageal junction viewed from clinical practice
      (discussion)].

PMID- 17230011
TI  - Orchidectomy increases beta-adrenoceptor activation-mediated neuronal nitric
      oxide and noradrenaline release in rat mesenteric artery.
AB  - BACKGROUND/AIMS: A previous study has demonstrated that endogenous male sex
      hormones do not alter neuronal nitric oxide (NO) release in rat mesenteric
      artery. However, the regulatory role of endogenous male sex hormones on
      noradrenaline (NA) release in rat mesenteric artery is not known. The present
      study was designed to analyze whether endogenous male sex hormones influence the
      NA release induced by electrical field stimulation (EFS), as well as the possible
      modification in NA and neuronal NO release by presynaptic beta-adrenoceptor
      activation. METHODS: For this purpose, mesenteric arteries from control and
      orchidectomized male Sprague-Dawley rats were used. Basal and EFS-induced
      neuronal NO and NA release, as well as the contractile effect induced by EFS, was
      measured. RESULTS: Basal and EFS-induced neuronal NO and NA release were similar
      in arteries from control and orchidectomized rats. The beta-adrenoceptor agonist
      clenbuterol did not modify EFS-induced neuronal NO and NA release in arteries
      from control rats. In contrast, in arteries from orchidectomized animals,
      clenbuterol increased both neuronal NO and NA release; this increase was
      prevented by incubation with the beta-adrenoceptor antagonist propranolol.
      However, the contractile response elicited by EFS was not modified by clenbuterol
      in either group of rats. CONCLUSIONS: These results show that orchidectomy does
      not alter the EFS-induced NA release. What is more, activation of presynaptic
      beta-adrenoceptors does not modify EFS-induced NA and neuronal NO release in
      arteries from control rats although it increases the release of both
      neurotransmitters in arteries from orchidectomized rats. Despite these
      modifications, the EFS-induced contractile response is preserved in arteries from
      orchidectomized rats.

PMID- 17230012
TI  - Primary amyloidosis involving mediastinal lymph nodes: diagnosis by
      transbronchial needle aspiration.
AB  - Amyloidosis is an uncommon disease caused by the deposition of abnormal proteins
      within soft tissues. Pulmonary and mediastinal lymph node involvement of the
      disease is rare. When mediastinal lymph nodes are affected, the diagnostic
      approach should include sample collection for pathological examination.
      Transbronchial fine needle aspiration is a useful and safe procedure for sampling
      mediastinal lymph nodes. This paper describes the first case of amyloidosis that
      involves mediastinal lymph nodes diagnosed by transbronchial needle aspiration.

PMID- 17230015
TI  - Diversity of brain morphology in teleosts: brain and ecological niche.
AB  - Modern teleosts have more copies of developmental regulatory genes than other
      vertebrates, probably due to a whole genome duplication that occurred
      specifically at the base of the lineage of ray-finned fishes. The genome
      duplication generates duplicated genes (including their regulatory regions), and
      one of the duplicates might become redundant and free from selective pressures.
      These redundant genes might be more easily mutated during evolution. Brain
      morphogenesis is a process that is dependent on a large genetic program in which
      a subprogram for the regionalization of the brain is coupled with that for cell
      proliferation control. If beneficial mutations took place in key genes within the
      genetic program for brain morphogenesis, it might result in the enhancement of
      region-specific cell proliferation and cell survival in the corresponding brain
      subdivisions. This mechanism might account for the appearance of various forms of
      teleost brains, which have been preserved under selection pressure in diverse
      environments. It is conceivable that variously modified brains might evolve under
      the conditions of natural selection so that the brains help fit the teleost
      species for diverse ecological niches.

PMID- 17230016
TI  - Developmental origin of diencephalic sensory relay nuclei in teleosts.
AB  - We propose here a novel interpretation of the embryonic origin of cells of
      diencephalic sensory relay nuclei in teleosts based on our recent studies of gene
      expression patterns in the medaka (Oryzias latipes) embryonic brain and
      comparative hodological studies. It has been proposed that the diencephalic
      sensory relay system in teleosts is unique among vertebrates. Teleost relay
      nuclei, the preglomerular complex (PG), have been assumed to originate from the
      basal plate (the posterior tuberculum) of the diencephalon, whereas relay nuclei
      in mammals are derived from the alar plate (dorsal thalamus) of the diencephalon.
      Our results using in situ hybridization show, however, that many pax6- or dlx2
      positive cells migrate laterally and ventrocaudally from the diencephalic alar
      plate to the basal plate during development. Massive clusters of the migrated
      alar cells become localized in the mantle layer lateral to the posterior
      tubercular neuroepithelium, from which main nuclei of the PG appear to
      differentiate. We therefore consider most if not all neurons in the PG to be of
      alar, not basal, origin. Thus, the teleost PG, at least in part, can be regarded
      as migrated alar nuclei. Developmental and hodological data strongly suggest that
      the teleost PG is homologous to a part of the mammalian dorsal thalamus. The
      organization and origin of the diencephalic sensory relay system might have been
      conserved across vertebrates.

PMID- 17230017
TI  - A new interpretation on the homology of the teleostean telencephalon based on
      hodology and a new eversion model.
AB  - Various hypotheses regarding the homology of the teleostean telencephalon with
      that of other vertebrates have been proposed to date. However, a firm conclusion
      on this issue has yet to be drawn. We propose here a new hypothesis with a new
      eversion model. Our hodological data and the analysis of dorsal telencephalic
      organization in adult cyprinids suggest that: (1) the area dorsalis pars
      posterior corresponds to the lateral pallium; (2) ventral region of area dorsalis
      pars lateralis to the medial pallium; (3) pars medialis, dorsal region of pars
      lateralis, pars dorsalis, and pars centralis of the area dorsalis to the dorsal
      pallium, and (4) nucleus taenia to the ventral pallium. We propose in a three
      dimensional model that the eversion process occurs not only dorsolaterally but
      also caudolaterally. We consider that the caudally directed component dominates
      for ventral zones of the pallium, or the lateral and ventral pallia; and the
      periventricular surface of these zones shift caudally, laterally, and then
      rostrally in teleosts with pronounced telencephalic eversion. This new model fits
      well with the putative homology based on hodology and the organization of
      telencephalic divisions in the adult brain.

PMID- 17230018
TI  - The sympathetic nervous system of anamniotes.
AB  - The sympathetic nervous system develops as an evolutionary trait with
      gnathostomes (jawed vertebrates), but not with agnathan fishes (i.e., hagfishes
      and lampreys). Organization of the sympathetic preganglionic neuronal columns is
      different in teleosts and anurans. In the teleosts so far examined, the majority
      of sympathetic preganglionic neurons (SPNs) are located in the dorsal part of the
      spinal central gray matter. In Tetraodontiformes, the cell column occupies only
      two rostral spinal segments, which are distinct in their cytoarchitecture and
      projections. On the other hand, the SPNs of anurans form two cell columns
      segregated mediolaterally. The lateral and medial columns are also distinct in
      their cytoarchitecture and projections. The neuroactive substances expressed in
      the SPNs both in teleosts and anurans are coded to the projections. In anurans,
      the SPNs containing gonadotrophin-releasing hormone and those containing
      calcitonin gene-related peptide are involved in the regulation of blood vessels
      and cutaneous glands, respectively. In the filefish, the SPNs containing galanin
      project specifically to non-adrenergic non-cholinergic postganglionic neurons in
      the cranial sympathetic ganglia. Therefore, both anuran and teleost systems have
      different morphological and chemical-coded patterns for functional variation,
      although the anuran sympathetic nervous system has more organizational similarity
      with that of amniotes.

PMID- 17230019
TI  - Ocular melatonin rhythms in teleost fish.
AB  - Melatonin (N-acetyl-5-methoxytryptamine) is synthesized in the pineal organ and
      the retina of vertebrates. In some teleost species, ocular melatonin levels can
      exhibit a circadian periodicity with elevated levels during the dark phase under
      light-dark (LD) cycles and this periodicity can persist even under constant dark
      (DD) cycles. However, reversed melatonin profiles and an absence of circadian
      ocular melatonin rhythms have also been reported. In this study, we investigated
      the daily rhythms of ocular melatonin in 32 teleost species under LD cycles. The
      melatonin profiles could be classified into three types: (1) normal profiles,
      with higher melatonin levels during the dark phase than the light phase; (2)
      reversed profiles, with higher levels during the light phase than the dark phase;
      (3) no significant differences in melatonin levels. We also studied whether
      ocular melatonin exhibits circadian rhythms under DD in selected species. Our
      results showed that ocular melatonin exhibited circadian rhythms in some but not
      all of the species examined. These results indicate that ocular melatonin rhythms
      in teleost fish exhibit species-specific variations as a result of the changes in
      the regulatory mechanisms during the course of evolution.

PMID- 17230020
TI  - Ion channels and their neural functions: contribution to general problems from
      studies of brains in non-mammalian species.
AB  - Ion channels and their neural functions have often been studied in the brains of
      mammals. However, the brains of some teleost fish species have special features
      that, at first glance, appear to be atypical and peculiar to that species alone.
      These teleost fish will contribute considerably to the understanding of general
      features of the ion channels and their neural functions. We have been interested
      in the neural mechanisms underlying the adaptive and flexible response of animals
      to changing environments and have been studying gonadotropin-releasing hormone
      (GnRH) peptidergic neuron systems, which we think are central for controlling
      such biologically adaptive responses. We have also been interested in a pretectal
      nucleus, corpus glomerulosum, which is tentatively regarded to play important
      roles in the organization of visually-guided feeding behaviors. In both systems,
      we found that certain types of apparently 'non-typical' Na(+) channels play
      important roles in neurobiological functions. Here we discuss how the study of
      functions of these apparently non-typical ion channels might contribute to our
      understanding of neural functions of vertebrate brains in general.

PMID- 17230021
TI  - Innervation of sonic muscles in teleosts: occipital vs. spinal nerves.
AB  - The innervation of sonic muscles in teleosts has been categorized into three
      types: occipital nerve, spinal nerve, and a combination of occipital and spinal
      nerves. The innervation patterns of sonic muscles were examined (or re-examined)
      in seven sonic fish species (rockfish, pinecone fish, sweeper, tigerfish,
      piranha, dory, and pollack) that use the sonic muscles to vibrate the
      swimbladder. The peripheral nerves (occipital or spinal) were identified based on
      skeletal preparations. The sonic muscle innervation was of the occipital type in
      four species (rockfish, pinecone fish, sweeper, and tigerfish) and of the spinal
      type in three species (piranha, dory, and pollack); none of the seven species
      examined showed the combination type. Therefore, we hypothesized that innervation
      patterns could be divided simply into occipital and spinal types. Moreover, the
      present results revealed that previously reported innervation patterns are
      inaccurate for three species (tigerfish, piranha, and dory) re-examined in this
      study. Therefore, it is important to define the peripheral nerves precisely, by
      using skeletal preparations, in future investigations of sonic muscle
      innervation.

PMID- 17230022
TI  - Central mechanisms underlying fish swimming.
AB  - Although the basic swimming rhythm is created by central pattern generators
      (CPGs) located in each spinal segment, command signals from the brain should be
      indispensable for the activation of CPGs to initiate swimming. We hypothesized
      that the nucleus of medial longitudinal fascicles (Nflm) is the midbrain
      locomotor region driving swimming rhythms in teleosts. To test this hypothesis,
      we recorded neuronal activities from Nflm neurons in swimming carp and analyzed
      the cytoarchitecture of the nucleus. We identified two types of Nflm neurons
      exhibiting electric activities closely related to swimming rhythms. Remarkably,
      tonic neurons that continued firing during swimming were found. The Nflm and
      neighboring oculomotor nucleus contain about 600 neurons in total, and among them
      as many as 500 were labeled retrogradely by an intraspinal tracer implantation
      and 400 neurons showed glutamatergic immunoreactivity. They are the most likely
      candidates for the descending neurons as the origin of driving signals that
      initiate swimming. Double-labeling experiments demonstrated direct connections of
      Nflm neurons to spinal neurons consisting of the CPG. These data imply that most
      Nflm neurons possibly exert an excitatory drive to the spinal CPGs through the
      descending axons with excitatory transmitter(s), probably glutamate. Furthermore,
      we confirmed that the caudal part of Nflm and the rostral part of the oculomotor
      nucleus overlap rostrocaudally by approximately 200 mum. In connection with the
      control of swimming by the brain, we carried out experiments to clarify the
      efferent system of the cerebellum of the goldfish. Cerebellar efferent fibers
      terminated in most brain regions except for the telencephalon. Importantly, the
      cerebellum projected also to the Nflm, suggesting the involvement of this brain
      region in the control of swimming. We have also determined that in the carp so
      called eurydendroid cells are cerebellar efferent neurons.

PMID- 17230023
TI  - Nerve ring of the hypostome in hydra: is it an origin of the central nervous
      system of bilaterian animals?
AB  - A hypothesis, 'the nerve ring in hydra shares a common origin with the central
      nervous system in bilaterian animals', is discussed in this review. The nerve
      ring of hydra is a ring of neurons whose neurites make a bundle running
      circumferentially around the hypostome just above the tentacle zone. This nervous
      structure has unique features in the hydra nervous system. It shows a tight
      association of neurons in contrast to the diffuse nerve net seen in other
      regions. It shows static developmental characters in contrast to the dynamic
      features of hydra nerve net present in other regions. Moreover, its structure and
      location are similar to the central nervous system (CNS) of other animals without
      a complex CNS such as nematodes and starfishes. Functions of the hydra nerve ring
      are also studied to test the hypothesis. The identified function is a crumpling
      of the tentacles, corresponding to the function of the inner nerve ring of
      hydrozoan jellyfish. The jellyfish nerve ring is considered to be a primitive
      central nervous system of radiates. Considering all the information available,
      the hypothesis is highly possible.

PMID- 17230024
TI  - Pantoprazole 40 mg is as effective as esomeprazole 40 mg to relieve symptoms of
      gastroesophageal reflux disease after 4 weeks of treatment and superior regarding
      the prevention of symptomatic relapse.
AB  - BACKGROUND/AIM: Little is known about the symptom course during and after
      treatment of gastroesophageal reflux disease (GERD). Here we address this
      question in patients with erosive GERD treated with pantoprazole or esomeprazole
      40 mg once daily using the validated reflux questionnaire ReQuest. METHODS: Of
      585 patients enrolled, 561 (intention-to-treat; ITT) patients with endoscopically
      confirmed GERD grades A-D (Los Angeles Classification) were randomized. To assess
      the GERD symptomatology, the patients completed the ReQuest daily, and analysis
      was done prior to (7 days), during (28 days), and after treatment (7 days). The
      mean scores (last 3 treatment days) of the subscale ReQuest-GI (gastrointestinal
      complaints) were compared between both groups. After the end of treatment, the
      number of symptom episodes and the rate of relapses were calculated. RESULTS:
      Noninferiority of pantoprazole versus esomeprazole during treatment was shown
      (mean ReQuest-GI score). During the posttreatment period, the proportion of
      patients experiencing a symptomatic relapse (51 vs. 61%, p = 0.0216, ITT) and the
      number of symptom episodes (0.56 vs. 0.74, p = 0.0095, ITT) were significantly
      lower on pantoprazole than on esomeprazole. CONCLUSIONS: Pantoprazole 40 mg was
      at least as effective as esomeprazole 40 mg for relieving GERD symptoms. During
      the posttreatment phase, patients on pantoprazole had a significantly lower risk
      to relapse and experienced significantly fewer symptom episodes.

PMID- 17230025
TI  - Further evidence of pleiotropy influencing speech and language: analysis of the
      DYX8 region.
AB  - BACKGROUND/AIMS: Genetic studies have raised the possibility of common bases for
      cognitive linguistic disorders such as speech sound disorder (SSD), reading
      disorder (RD) and language impairment (LI). Thus, some of the same genes may
      jointly influence cognitive components within and between these three disorders.
      We examined the plausibility of this theory in a sample of families ascertained
      on the basis of a child with SSD. METHODS: Using the method of generalized
      estimating equations to solve a bivariate family predictive model we obtained
      measures of comorbidity and familial aggregation of SSD and LI. We then used two
      methods of multipoint model-free linkage analysis to evaluate SSD and LI
      psychometric test measures over a region previously implicated in linkage studies
      of RD, DYX8 region, 1p34-p36. RESULTS: Bivariate phenotypic analyses show
      evidence of comorbidity and within family aggregation and coaggregation of SSD
      and LI. In addition, two regions on chromosome 1 show suggestive evidence of
      linkage. The first region was previously reported in dyslexia studies. Our
      maximum linkage signal in this region measured articulation (p = 0.0009) in SSD
      sibling pairs. The second region is characterized by processes involved in
      language production, with the maximum linkage signal measuring listening
      comprehension (p = 0.0019) using all sibling pairs. CONCLUSION: We conclude that
      the DYX8 region could bear genes controlling pleiotropic effects on SSD, LI and
      RD.

PMID- 17230026
TI  - An overview of neurological disorders in Wales.
AB  - This pragmatic work was undertaken to assist commissioners of health services in
      Wales in their planning for future provision of services for neurological and
      neurosurgical patients. A literature search, which was carried out to ascertain
      the epidemiology of neurological and neurosurgical disorders in Wales, revealed
      limited epidemiological surveys of patients in Wales, while other literatures
      although outdated were still relevant. More recent national reports, published by
      professional bodies and patients' organisations, were also identified. These
      disorders were also grouped according to their aetiology and symptoms into 13
      groups. Using all the available literature, total estimates of annual incidence
      and point prevalence of these disorders were arrived at. We can conclude that
      approximately 5.8% of the population in Wales are affected by neurological and
      neurosurgical disorders that include headaches, traumatic and infectious diseases
      of the nervous system.

PMID- 17230027
TI  - Winter excess in hospital admissions, in-patient mortality and length of acute
      hospital stay in stroke: a hospital database study over six seasonal years in
      Norfolk, UK.
AB  - BACKGROUND: Several studies have examined the incidence and mortality of stroke
      in relation to season. However, the evidence is conflicting partly due to
      variation in the populations (community vs. hospital-based), and in climatic
      conditions between studies. Moreover, they may not have been able to take into
      account the age, sex and stroke type of the study population. We hypothesized
      that the age, sex and type of stroke are major determinants of the presence or
      absence of winter excess in morbidity and mortality associated with stroke.
      METHODS: We analyzed a hospital-based stroke register from Norfolk, UK to examine
      our prior hypothesis. Using Curwen's method, we performed stratified sex-specific
      analyses by (1) seasonal year and (2) quartiles of patients' age and stroke
      subtype and calculated the winter excess for the number of admissions, in-patient
      deaths and length of acute hospital stay. RESULTS: There were 5,481 patients
      (men=45%). Their ages ranged from 17 to 105 years (median=78 years). There
      appeared to be winter excess in hospital admissions, deaths and length of acute
      hospital stay overall accounting for 3/100,000 extra admissions (winter excess
      index of 3.4% in men and 7.6% in women) and 1/100,000 deaths (winter excess index
      of 4.7 and 8.6% in women) due to stroke in winter compared to non-winter periods.
      Older patients with non-haemorrhagic stroke mainly contribute to this excess. If
      our findings are replicated throughout England and Wales, it is estimated that
      there are 1,700 excess admissions, 600 excess in-patient deaths and 24,500 extra
      acute hospital bed days each winter, related to stroke within the current
      population of approximately 60 million. CONCLUSIONS: Further research should be
      focused on the determinants of winter excess in morbidity and mortality
      associated with stroke. This may subsequently reduce the morbidity and mortality
      by providing effective preventive strategies in future.

PMID- 17230029
TI  - Decline in cognitive functioning is associated with a higher mortality risk.
AB  - OBJECTIVE: This study investigates the association between 5-year change in
      cognitive functioning and subsequent mortality. METHODS: Four hundred and ninety
      three Dutch and Italian men from the Finland, Italy, and the Netherlands Elderly
      (FINE) Study, born between 1900 and 1920, participated in the present study
      between 1990 and 2000. Cognitive functioning was measured with the Mini-Mental
      State Examination in 1990 and 1995, and mortality data were obtained until the
      year 2000. A proportional hazard analysis was used to investigate the association
      between 5-year change in cognitive functioning and subsequent 5-year mortality.
      Adjustments were made for age, education, country, lifestyle factors, prevalence
      of chronic diseases and, additionally, for baseline cognitive functioning.
      RESULTS: Men whose cognition decreased (more than 1 standard deviation) between
      1990 and 1995 had a 2-fold higher risk of dying in the following 5 years compared
      with men whose cognition was stable (adjusted hazard ratio=1.9; 95% confidence
      interval 1.3-2.7). Mortality risk of men whose cognition improved between 1995
      and 2000 was not different from men whose cognition was stable (adjusted hazard
      ratio=1.1, 95% confidence interval 0.7-1.9). CONCLUSION: A decline in cognitive
      functioning is associated with a higher mortality risk.

PMID- 17230028
TI  - Inpatient and community ischemic strokes in a university hospital.
AB  - BACKGROUND: Previous studies have shown that inpatient strokes are common and
      severe. We sought to characterize the risk factors, stroke subtypes, timing of
      acute stroke evaluation and frequency of thrombolytic therapy in inpatient
      ischemic strokes compared with community ischemic strokes. DESIGN/METHODS: The
      hospital records of patients admitted for acute ischemic stroke between 1996 and
      2002 were reviewed. Acute stroke was defined as occurrence of stroke symptoms
      within 72 h, and in-hospital status was assigned if the patient was currently
      admitted for another illness at the time of the stroke. Patient demographics such
      as medical versus surgical service, admission diagnoses, clinical features
      including stroke risk factors, access to thrombolytic therapy and immediate
      outcome were analyzed. RESULTS: Of 947 patients with acute ischemic stroke, 161
      (17.0%) had strokes occurring while already in the hospital (IHIS), compared to
      786 (83%) that occurred in the outpatient community (CIS). Approximately two
      thirds of IHIS occurred on medical services (102, 63.4%) and one third on
      surgical services (59, 36.7%). Mean age, male gender, atherothrombotic etiology
      and risk factors including hypertension, diabetes and smoking history were of
      similar frequencies in IHIS and CIS, but penetrating artery disease was the cause
      of only 5.6% of IHIS compared to 21.8% of CIS (p<0.0001). The mean modified
      Rankin scale for IHIS at presentation was 4.33 +/- 0.74, compared to 3.67 +/-
      1.03 for CIS (p<0.0001). Of 161 IHIS patients, 21 (13.0%) had neurological
      assessment within 3 h of symptom onset, compared to 16.0% of CIS patients
      (p=0.403, n.s.), and the rate of thrombolytic therapy was not significant between
      IHIS (3.7%) and CIS (5.6%) patients. CONCLUSIONS: IHIS are common and severer
      than CIS. The use of thrombolytic therapy in IHIS patients was limited because of
      time of recognition and inpatient-associated conditions. Increased vigilance for
      timely neurological assessment of these patients is warranted.

PMID- 17230030
TI  - Mirtazapine enantiomers in blood and cerebrospinal fluid.
AB  - Little information exists on the concentrations of recent antidepressants and
      their metabolites in cerebrospinal fluid (CSF). Using a stereoselective method,
      we measured plasma and CSF levels of mirtazapine (MIR), N-demethylmirtazapine and
      8-OH-MIR in 3 depressed patients treated with racemic MIR (45 mg/day) for 4
      weeks. S-(+)-MIR is considered to be the antidepressant enantiomer, but only R-(
      )-MIR reached measurable concentrations in CSF. For R-(-)-MIR, the CSF/plasma
      ratio varied between 0.08 and 0.31. Further studies are needed to test the
      hypothesis that there are possible differences in the transport mechanisms of the
      enantiomers of MIR at the blood-CSF barrier.

PMID- 17230031
TI  - No allele variation of the MAOA gene promoter in male Chinese subjects with
      attention deficit hyperactivity disorder.
AB  - The aim of the current study was to examine any difference in the repeat sequence
      of the monoamine oxidase A (MAOA) gene promoter between males with attention
      deficit hyperactivity disorder (ADHD) and randomly selected subjects in a
      community. The role of the MAOA gene promoter in ADHD cases was also
      investigated. The total of 244 participants included 57 male ADHD subjects as the
      case group and 187 males, also in southern Taiwan, as the community controls.
      There was no significantly different distribution in the repeat sequence of the
      MAOA gene promoter (chi2 = 3.895, d.f. = 3, p = 0.273), and no significantly
      different distribution of 'long-form' and 'short-form' alleles between the ADHD
      group and the male community group was noted (chi2 = 2.484, d.f. = 1, p = 0.115).
      Some aspects of clinical response are mentioned in the discussion of this study
      which are worth exploring further in the future.

PMID- 17230032
TI  - Escitalopram in the long-term treatment of major depressive disorder in elderly
      patients.
AB  - AIM: The primary aim was to investigate the long-term safety and tolerability of
      escitalopram (10 or 20 mg/day) treatment of elderly patients suffering from major
      depressive disorder. The secondary aim was to examine response to treatment, as
      measured by change in the Montgomery-Asberg Depression Rating Scale (MADRS) total
      score from study entry to each visit, using observed cases. METHOD: This
      extension trial included 225 patients who had completed an 8-week, double blind,
      placebo-controlled lead-in study, which was performed in outpatients in primary
      care and in specialist clinics. The intent-to-treat population comprised 223
      patients. RESULTS: The overall withdrawal rate was 24%. The most common reason
      for withdrawal was adverse events (9%). The 5 most common adverse events were
      accidental injury, rhinitis, weight increase, arthralgia and coughing, with an
      incidence ranging from 8 to 13%. No new types of adverse events were reported in
      this extension study compared to the 8-week lead-in study. The mean weight
      increased from 69.7 kg at study entry to 70.3 kg at endpoint. The percentage of
      patients in remission (MADRS total score < or = 12) increased from 48% at study
      entry to 72% by week 52. CONCLUSION: Escitalopram demonstrated a favourable
      tolerability profile during 52 weeks of open-label treatment of elderly patients,
      with further improvement in depressive symptoms.

PMID- 17230033
TI  - Association of GABRB3 polymorphisms with autism spectrum disorders in Korean
      trios.
AB  - BACKGROUND/AIMS: Autism spectrum disorders (ASD) are complex neuropsychiatric
      disorders having a genetic risk factor. The association and linkage study for the
      gamma-aminobutyric acid type A receptor beta3 subunit gene (GABRB3), located
      within the chromosome 15q11-q13 autism candidate region, and ASD have been
      evaluated. The aim of this study was to investigate the association between
      GABRB3 and ASD in the Korean population. METHODS: The present study was conducted
      with the detection of four single-nucleotide polymorphisms (rs1426217, rs2081648,
      rs890317, rs981778) in GABRB3 and association analysis in 104 Korean ASD trios
      using the transmission disequilibrium test. RESULTS: The transmission
      disequilibrium test demonstrated that an allele at rs2081648 showed preferential
      transmission (p = 0.027). One haplotype, including all examined markers in
      GABRB3, demonstrated significant association (p = 0.043), but the global chi2
      test for haplotype transmission did not reveal an association between GABRB3 and
      ASD (chi2 = 15.516, d.f. = 15). CONCLUSION: Our finding suggested that single
      nucleotide polymorphisms in GABRB3 may play a significant role in the genetic
      predisposition to ASD in the Korean population.

PMID- 17230034
TI  - Performance in the Wisconsin Card Sorting Test and the C957T polymorphism of the
      DRD2 gene in healthy volunteers.
AB  - INTRODUCTION: Previous studies have associated a decreased striatal D2 dopamine
      receptor (DRD2) binding with impaired performance in cognitive tasks. In vivo
      studies have found a lower DRD2 binding associated with the CC genotype of the
      C957T single nucleotide polymorphism (SNP) of the DRD2 gene. OBJECTIVE: The aim
      of this study was to investigate the relationship between executive functions and
      the C957T DRD2 SNP. We hypothesized that the CC genotype would be associated with
      a poorer executive functioning. METHODS: Our sample consisted of 83 healthy
      volunteers (28 males and 55 females; mean age 25.2, SD 1.7 years). To assess
      executive functions, the Wisconsin Card Sorting Test was used, considering the
      variables perseverative errors, perseverative responses, and number of categories
      achieved. The genotype distribution was 13 CC, 41 CT, and 29 TT, satisfying Hardy
      Weinberg equilibrium. RESULTS: Carriers of the CC genotype, compared with
      carriers of the CT/TT genotypes, achieved significantly fewer categories (5.00
      vs. 5.81; p = 0.004), made a greater number of perseverative errors (13.46 vs.
      8.39; p = 0.018), and had a greater number of perseverative responses (14.92 vs.
      8.94; p = 0.014). CONCLUSIONS: Our results support the hypothesis that the C957T
      DRD2 SNP may influence cognitive performance through its repercussions on central
      dopaminergic function.

PMID- 17230035
TI  - No association between dorsolateral prefrontal gray matter deficit and N-acetyl
      aspartate ratios in schizophrenia.
AB  - The cellular substrates of cortical volume deficit in schizophrenia are unclear.
      We may hypothesize that, if that deficit was related to a decrease in the amount
      in neuronal tissue, it should correlate with N-acetyl aspartate levels. We
      studied a group of 34 schizophrenia patients (of them, 17 first episodes) with
      both structural and spectroscopic magnetic resonance (MR). Using the data of 50
      controls, we were able to calculate for each case residuals of gray matter and
      cortical cerebrospinal fluid (CSF) in the dorsolateral prefrontal (DLPF) region,
      representing the deviation from the expected values in normals, given individual
      intracranial volume and age. Although our patients showed a significant deficit
      in gray matter and excess in cortical CSF in the DLPF region, that deficit was
      unrelated to N-acetyl aspartate levels. This was also true for the chronic and
      first episode groups analyzed separately. These results do not support a neuronal
      tissue deficit as contributing to the cortical volume deficit in schizophrenia,
      at least in the DLPF region.

PMID- 17230036
TI  - Modifications produced by indomethacin and L-NAME in the effect of ultralow-dose
      aspirin on platelet activity in portal hypertension.
AB  - In our previous study, we demonstrated the effect of ultralow-dose aspirin (ULDA)
      on platelet activity and bleeding in rats with portal hypertension (PHT) produced
      by portal vein ligation (PVL). This paper reports modifications in this effect
      caused by blocking NO production by nitro arginine methyl ester (NAME) and
      cyclooxygenase (COX) activity with indomethacin. PVL rats and sham-operated
      controls were treated with placebo, indomethacin or NAME and 30 min thereafter
      with placebo or ULDA treatment. Platelet activity was studied by a model of in
      vivo laser-induced thrombus production in the mesenteric circulation, induced
      hemorrhage time (IHT) and platelet aggregation ex vivo induced by adenosine
      diphosphate in an aggregometer. The PVL group receiving placebo showed a
      decreased platelet activity with prolonged IHT, an effect that was reversed by
      ULDA. Indomethacin induced a decreased platelet activity in the control rats and
      a prolonged IHT. In PHT with ULDA, in vivo platelet activity was enhanced but the
      normalization of IHT observed in rats without indomethacin was blunted. The
      addition of NAME normalized the diminished in vivo platelet aggregation and
      increased the IHT observed in PVL animals. These changes decreased the effect of
      ULDA in both sham-operated and PVL animals. The effect of indomethacin was more
      clearly modified by ULDA than the effect of NAME, thus suggesting that
      modifications in the COX pathway might alter the effect of ULDA. The simultaneous
      administration of indomethacin and ULDA could inhibit its beneficial effect on
      bleeding in rats with PHT.

PMID- 17230037
TI  - Effects of external electrical stimulation on laser-beam-induced experimental
      thrombosis.
AB  - External electrical stimulation (EES) has demonstrated venous antithrombotic
      properties. The aim of this investigation was to study its antithrombotic
      properties using unfractionated heparin (UFH) as a reference in arterial and
      venous mesenteric microvessels. For this purpose a rat model of laser-beam
      induced thrombosis was used. Four groups of rats were investigated (n = 7):
      control, UFH (5 mg /kg), UFH (2.5 mg/kg) and electrical stimulation [e-vascular,
      E = 10, alternate polarity, in two protocols: (i) 30 min before and during
      thrombosis induction and (ii) only 30 min before thrombosis induction as
      preventive stimulation]. This effect was tested in arterial and venous
      microvessels in the four groups using the continuous protocol and only in
      arterial microvessels using the preventive protocol. Three parameters were
      studied: the number of laser beams needed to induce platelet thrombus formation,
      the number of emboli and the duration of embolization. Induced hemorrhagic time
      (IHT), platelet aggregation induced by ADP and coagulation tests (activated
      partial thromboplastin time, aPTT, prothrombin time, pTT, and fibrinogen level)
      were also determined. Continuous electrical stimulation decreased the number of
      emboli and the duration of embolization both in arterioles and in venules. It
      also significantly reduced the amplitude and velocity of the ex vivo platelet
      aggregation induced by ADP. Contrary to UFH, neither aPTT nor pTT were affected
      in platelet-poor plasma collected after the induction of thrombosis by laser
      beam, nor did it modify IHT. Preventive electrical stimulation produced similar
      results with fewer effects on induced venous thrombosis. These data suggest that
      EES has a potent antithrombotic effect on arterial and venous thrombosis without
      any hemorrhagic adverse effects, making it a very promising tool in the
      prevention and treatment of venous and arterial thromboembolic complications.

PMID- 17230038
TI  - Functional analysis of the factor IX epidermal growth factor-like domain mutation
      Ile66Thr associated with mild hemophilia B.
AB  - The present study focused on the functional role of the mutation Ile66Thr located
      in the N-terminal epidermal growth factor-like domain of coagulation factor IX
      (FIX). This mutation causes mild hemophilia B with approximately 25% FIX
      coagulant activity and FIX antigen levels of around 90% of normal. In the 3
      dimensional structure of porcine FIXa and in the subsequent 3-dimensional model
      of human FIXa that we have previously developed, residue 66 is exposed to the
      solvent and can be replaced by many amino acids, including Thr, without affecting
      the major folding/stability of the molecule. This is consistent with the
      basically normal antigen levels observed. We found that the FIX Ile66Thr mutant
      was activated to a normal extent by FVIIa/TF and FXIa. However, the ability of
      FIX Ile66Thr to activate FX was impaired in both the presence and absence of
      FVIIIa, indicating that Ile66 is not directly involved in the binding of FIX to
      FVIIIa.

PMID- 17230039
TI  - Relationship between platelet indexes and coronary angiographic findings in
      patients with ischemic heart disease.
AB  - To understand the mechanisms linking platelets to the risk of coronary artery
      disease, we investigated the relation between coronary angiographic morphology
      and platelet indexes--platelet count, mean platelet volume (MPV), platelet-large
      cell ratio (P-LCR) and platelet distribution width (PDW)--in patients with
      ischemic heart disease. Eighty-four patients with ischemic heart disease and 120
      aged controls (AC) were enrolled in the study. The patients without any signs of
      acute myocardial infarction and acute coronary syndromes who underwent coronary
      angiography were divided into two groups, an 'angiographically negative group'
      (group 0) and an 'angiographically positive group' (group 1), with positive
      coronary obstruction depending on the diagnostic criteria in our hospital.
      Platelet indexes were measured in peripheral venous blood. The mean platelet
      counts were significantly lower in groups 1 and 0 than in AC (p = 0.0128 and p =
      0.0041, respectively). MPV, P-LCR and the PDW were significantly higher in group
      0 than in group 1 and AC (p = 0.0352 and 0.0433, p = 0.0059 and 0.0052, p =
      0.00461 and 0.0146, respectively). The indexes of group 1 were almost the same
      compared with AC with respect to MPV, P-LCR and PDW. In conclusion, these
      findings suggest that the measurement of platelet indexes may reflect the
      underlying pathophysiological state and subsequent clinical events in the
      patients. In particular, lower P-LCR seems to identify patients with positive
      coronary angiography.

PMID- 17230040
TI  - Mechanism of the antithrombotic effect of dietary diacylglycerol in atherogenic
      mice.
AB  - INTRODUCTION: We have shown earlier that diacylglycerol (DAG) but not
      triacylglycerol (TAG) inhibited thrombus formation. The aim of the present study
      was to investigate the mechanism of this antithrombotic effect of DAG. MATERIALS
      AND METHODS: Four different diets, the (1) Western-style high-fat diet (HFD)
      containing 20% lipid and 0.05% cholesterol (w/w), (2) TAG-rich and (3) DAG-rich
      HFDs containing 20% lipid and 0.05% cholesterol, but all lipid replaced by TAG or
      DAG oil with very similar fatty acid composition and the (4) Japanese-style low
      fat diet (LFD) containing 7% oil but no cholesterol were given to apolipoprotein
      E and low-density lipoprotein (LDL) receptor double-deficient mice.
      Atherogenicity was assessed by morphology, mapping the whole aorta and measuring
      the total area of lipid-stained lesions. Endothelial function was measured by the
      flow-mediated vasodilation test. Platelet reactivity was assessed from native
      blood sample by a shear-induced platelet function test (hemostatometry). Serum
      lipoprotein profile was measured by HPLC. RESULTS: Both the Western-style and the
      TAG-rich HFDs have accelerated atherosclerosis. In contrast, DAG-rich HFD
      inhibited the atherosclerotic process to an extent comparable with the Japanese
      style LFD. There was no significant difference in platelet and coagulant activity
      between the studied diet groups. DAG-rich but not the TAG-rich HFD significantly
      suppressed serum LDL cholesterol level. CONCLUSIONS: The present findings suggest
      that the mechanism of antithrombotic and anti-atherogenic effect of DAG may
      involve the protection of the vascular endothelium from injury and lowered serum
      LDL cholesterol.

PMID- 17230041
TI  - Relationship between hemostatic factors and the platelet index in patients with
      ischemic heart disease.
AB  - To understand the heterogeneity of platelets, we investigated the correlation
      between hemostatic factors and the platelet index [platelet count, mean platelet
      volume (MPV), platelet-large cell ratio (P-LCR) and platelet distribution width
      (PDW)] in patients with ischemic heart disease (IHD). Ninety-seven patients with
      IHD and 120 aged controls (AC) were enrolled in the study. D-dimer, thrombin
      antithrombin III complex (TAT), von Willebrand factor antigen (VWF:Ag) and
      platelet indexes were measured in the peripheral venous blood. The D-dimer and
      TAT levels in the patients were significantly elevated compared to the AC. VWF:Ag
      was also elevated, but not significantly so. However, no differences were
      observed in the platelet index between the patients and the AC. In the patients,
      the level of VWF:Ag was significantly inversely correlated with the platelet
      count, but such correlations were not observed in the D-dimer and TAT. TAT was
      significantly positively correlated with MPV, P-LCR and PDW. VWF:Ag was also
      correlated, though not significantly, with MPV, P-LCR and PDW. The D-dimer was
      not correlated with the platelet index. In the AC, the platelet count was
      inversely correlated with VWF:Ag, but not significantly so. VWF:Ag showed
      significant positive correlations with MPV, P-LCR and PDW. However, the D-dimer
      and TAT were not correlated with the platelet index in AC. These findings suggest
      that VWF:Ag and TAT seem to be profoundly related to platelet volume.

PMID- 17230042
TI  - Mutations and polymorphisms in genes affecting haemostasis components in children
      with thromboembolic events.
AB  - The distribution of mutations/polymorphisms in genes affecting haemostasis
      [factor V Leiden (FVL), FV H1298R (FVR(2)), FII 20210A, b-Fib 455G-->A, FXIII
      V34L, PAI-1 4G, HPA-1b] among 141 children with thrombosis at various sites and
      103 controls was compared. Additionally, the carriage of these
      mutations/polymorphisms was associated with the levels of their corresponding
      proteins in thrombosed children. Thrombosis was more frequent in boys (p =
      0.021). No studied mutation/polymorphism was found to be a risk factor for
      thrombosis, except for FVL (odds ratio 3.8, 95% CI 1.4-10.6). The risk of
      thrombosis for FVL carriers was twice as high in children with an idiopathic
      thrombosis (odds ratio 5.4) than in thrombosed children with an underlying
      disease or a triggering event (odds ratio 2.7). FVL carriers had an odds ratio of
      5.9 (95% CI 1.8-19.6) when FVR(2) was absent. In thrombosed children, the
      activated protein C resistance ratio was significantly lower in the presence of
      FVL (p < 0.001). Prothrombin and fibrinogen levels, although higher in FII 20210A
      and b-Fib 455G-->A carriers, did not reach statistical significance.

PMID- 17230043
TI  - An experimentally antithrombotic strawberry variety is also effective in humans.
AB  - Prevention of arterial thrombotic diseases is of high priority in developed
      countries. As inappropriate diet is regarded as an important risk factor of
      thrombotic events, daily intake of an antithrombotic diet may offer a convenient
      and effective way of prevention. Earlier we used animal models of thrombosis to
      find fruits and vegetables with potential antithrombotic activity. Among various
      strawberry varieties tested, a particular variety (KYSt-4, Nohime) showed a
      significant antithrombotic effect. The aim of the present investigation was to
      extend this study to humans, by testing the experimentally active KYSt-4 and
      inactive KYSt-10 variety for effectiveness in humans after oral intake. Filtrates
      of strawberries were prepared and administered orally. Thrombotic status was
      tested by a novel global test (Gorog Thrombosis Test). The strawberry variety
      (KYSt-4; Nohime) which earlier inhibited experimental thrombosis showed
      antithrombotic effects in humans, while the experimentally inactive variety (KYSt
      10) as well as the relevant control (water) were ineffective.

PMID- 17230045
TI  - Three modes of platelet degranulation?

PMID- 17230044
TI  - Successful management of massive intraperitoneal bleeding in a hemophilia A
      patient with inhibitor by surgical debridement of the incomplete hematoma and
      administration of recombinant factor VIII and activated factor VII.

PMID- 17230046
TI  - The manic-depressive spectrum and mood stabilization: Kraepelin's ghost.

PMID- 17230047
TI  - Is there a continuity between bipolar and depressive disorders?
AB  - BACKGROUND: Recent studies questioned the current categorical split of mood
      disorders into bipolar disorders (BP) and depressive disorders (MDD). METHODS:
      Medline database search of papers from the last 10 years on the categorical
      dimensional classification of mood disorders. Various combinations of the
      following key words were used: mood disorders, bipolar, unipolar, major
      depressive disorder, spectrum, category/categorical, classification, continuity.
      Only English language clinical papers were included, review papers were excluded,
      similar papers selected by quality. The number of papers found was 1,141. The
      number of papers selected was 109. RESULTS: The continuity/spectrum between BP
      (mainly BP-II) and MDD was supported by the following findings:(1) high frequency
      of mixed states (mixed mania, mixed hypomania, mixed depression, i.e. co
      occurring depression and noneuphoric manic/hypomanic symptoms) because opposite
      polarity symptoms in the same episode do not support a hypomania/mania-depression
      splitting; (2) MDD was the most common mood disorder in BP probands' relatives;
      (3) no bimodal distribution of distinguishing symptoms between BP and MDD; (4)
      bipolar signs not uncommon in MDD; (5) many MDD shifting to BP; (6) many lifetime
      manic/hypomanic symptoms in MDD; (7) correlation between lifetime manic/hypomanic
      symptoms and MDD symptoms; (8) hypomania factors in MDD; (9) MDD often recurrent;
      (10) similar cognitive style. The categorical distinction between BP (mainly BP
      I) and MDD was supported by the following findings: (1) BP more common in BP
      probands' relatives; (2) lower age at BP onset; (3) females as common as males in
      BP-I, more common than males in MDD; (4) BP-I depression more atypical and
      retarded, MDD depression more sleepless and agitated; (5) BP more recurrent.
      CONCLUSIONS: Focusing on mood spectrum's extremes (BP-I vs. MDD), a categorical
      distinction seems supported. Focusing on midway disorders (BP-II and MDD plus
      bipolar signs), a continuity/spectrum seems supported. Results seem to support
      both a categorical and a dimensional view of mood disorders.

PMID- 17230048
TI  - Bipolar (spectrum) disorder and mood stabilization: standing at the crossroads?
AB  - Diagnosis and treatment of bipolar disorder has long been a neglected discipline.
      Recent years have shown an upsurge in bipolar research. When compared to major
      depressive disorder, bipolar research still remains limited and more expert based
      than evidence based. In bipolar diagnosis the focus is shifting from classic
      mania to bipolar depression and hypomania. There is a search for bipolar
      signatures in symptoms and course of major depressive episodes. The criteria for
      hypomania are softened, leading to a bipolar prevalence that now equals that of
      major depressive disorder. Anti-epileptics and atypical antipsychotics have
      joined lithium in the treatment of bipolar disorder. Fortunately, mood
      stabilization has become the core issue in bipolar disorder treatment. In
      contrast with recent trends in the diagnosis of bipolar disorder, treatment
      research remains more focused on classic mania than depression or hypomania. This
      leaves the clinician with the difficult task of diagnosing 'new bipolar patients'
      for whom no definite evidence-based treatment is available. An important efficacy
      effectiveness gap further compromises the translation of the evidence base on
      bipolar disorder treatment into clinical practice. The recent upsurge of research
      on bipolar disorder is to be applauded, but further research is needed: for
      bipolar disorder in general, and for bipolar depression and the long-term
      treatment specifically. Given the complexity of the disorder and the many
      clinical uncertainties, effectiveness studies should be installed.

PMID- 17230049
TI  - Improving volitional competence is crucial for the efficacy of psychosomatic
      therapy: a controlled clinical trial.
AB  - BACKGROUND: Although skills of will (volitional competences), such as self
      motivation or emotion regulation, are particularly necessary for patients with
      psychiatric and psychosomatic disorders, it is unknown whether volitional
      deficits can be reduced and thereby the efficacy of psychotherapy increased. We
      investigated the effect of a group therapy for improving volitional competence in
      an inpatient rehabilitation program. METHODS: In a controlled clinical trial,
      patients from a rehabilitation clinic participated either in the volition group
      therapy in addition to the standard cognitive behavioral therapy (volition group,
      VG) or in the standard cognitive behavioral therapy (standard group, SG).
      Patients were tested for volitional competence, depressive symptoms, total
      psychiatric symptomatology, and physical complaints prior to, at the end of
      inpatient therapy and after 6 months of follow-up (n = 242). RESULTS: At the end
      of inpatient therapy, better improvement in volitional competence was observed in
      the VG than in the SG [e.g. self-motivation: effect size (ES) 0.96 vs. 0.39;
      ANCOVA: F(1, 209) = 16.58; p < 0.001]. Patients with greater volitional
      improvements had a better rehabilitation outcome. In the VG, depressive symptoms
      as well as total psychiatric symptomatology decreased significantly more than in
      the SG [ES: 1.18 vs. 0.87, F(1, 207) = 4.68, p < 0.05, and ES 1.12 vs. 0.73, F(1,
      205) = 4.68, p < 0.05, respectively], but not physical complaints [ES: 0.62 vs.
      0.48, F(1, 207) = 1.08, n.s.]. CONCLUSIONS: Effect size increased in patients
      with initially low volitional competence and high motivation to participate in a
      volitional training. These results might lead to a more systematic assessment and
      training of volitional competence.

PMID- 17230050
TI  - Cue exposure therapy for the treatment of opiate addiction: results of a
      randomized controlled clinical trial.
AB  - BACKGROUND: Persistent cue reactivity to drug-related stimuli is a well-known
      phenomenon among abstinent drug users and has been found to be a predictor of
      relapse. Cue exposure therapy (CET) aims to reduce this cue reactivity by
      exposing abstinent drug users to conditioned drug-related stimuli while
      preventing their habitual response, i.e. drug use. METHODS: 127 abstinent heroin
      dependent Dutch inpatients were randomized to CET (n = 65; 55 completers) and
      placebo psychotherapy treatment (PPT) (n = 62; 59 completers). It was examined
      whether CET would lead to a decrease in drug-related cue reactivity (using mixed
      design ANOVA) and subsequently to lower dropout and relapse rates (using logistic
      regression) compared to PPT. RESULTS: Both groups responded with a similar
      decrease in self-reported cue reactivity (craving, mood). The CET group did show
      a significant decrease in physiological reactivity (skin conductance) compared to
      PPT. However, dropout and relapse rates were, contrary to our expectations,
      significantly higher in the CET group. CONCLUSIONS: This is the first randomized
      controlled trial showing that CET, compared to a non-specific psychotherapy,
      might increase dropout and relapse rates among abstinent heroin-dependent clients
      in a drug-free setting. Caution is warranted when applying CET in this specific
      context.

PMID- 17230051
TI  - Grief and post-traumatic growth in parents 2-6 years after the death of their
      extremely premature baby.
AB  - OBJECTIVE: To assess grief and post-traumatic growth in parents 2-6 years after
      the death of a premature baby (24-26 weeks' gestation) and to evaluate Pictorial
      Representation of Illness and Self-Measure (PRISM) in the assessment of
      bereavement. METHOD: Fifty-four parents were assessed for their experiences
      during hospitalization and by questionnaires regarding grief (MTS), post
      traumatic growth, affective symptoms and the visual representation of the baby
      and the self of the parents (PRISM). RESULTS: Even 2-6 years after the loss of
      their extremely preterm infant the parents still suffer a lot from their
      bereavement, mothers more so than fathers (Mann-Whitney U test, U = 230.5, p <
      0.05). Having another child reduced the level of grief (U = 119.0, p < 0.05).
      Mothers showed more post-traumatic growth than fathers (U = 140.5, p < 0.001).
      For all parents a shorter distance between the baby and the self (PRISM)
      correlated with greater grief (rho = -0.62, p < 0.001); in multiple regression
      analysis MTS explained 38% of the SBS-variance. CONCLUSIONS: Clinicians should be
      aware that the death of an extremely premature infant triggers not only a painful
      long-term process of mourning but also of individual personal growth. Adaptation
      processes after the death differ depending on gender, with mothers experiencing
      more intense grief but also more growth than fathers. The modified PRISM test is
      recommended as a visual, non-verbal and easy-to-use instrument to assess
      bereavement.

PMID- 17230052
TI  - Pain response in depersonalization: a functional imaging study using hypnosis in
      healthy subjects.
AB  - BACKGROUND: Depersonalization (DP) is characterized by persistent or recurrent
      episodes of detachment from one's self with reduced pain perception being a
      common feature. Alterations in the body schema similar to the cortico-limbic
      disconnection syndrome of pain asymbolia are suggested to be responsible for DP.
      In this study we used hypnosis to induce DP in healthy subjects and to examine
      neural patterns of pain perception in the state of DP by means of functional
      magnetic resonance imaging (fMRI). METHODS: Pain perception was investigated in 7
      healthy subjects with high susceptibility to hypnosis in three different mental
      states: waking state (N-W), hypnotic relaxation (H-R) and hypnotic DP (H-DP).
      Pain was induced with electrical stimulation to the median nerve at the right
      wrist. fMRI measurements were performed during all states. RESULTS: Nociceptive
      stimuli led to an activation of the well described pain network including
      somatosensory and insular regions and the cerebellum. Activation was markedly
      reduced in the contralateral somatosensory cortex, parietal cortex (Brodmann area
      40, BA40), prefrontal cortex (BA9), putamen and the ipsilateral amygdala during H
      DP. Subjects also reported a significant decrease in pain intensity from N-W to H
      DP. CONCLUSION: Pain response during H-DP was reduced in sensory and affective
      pain-related areas, reflecting the diminished intensity of the perceived pain.
      Moreover, a network of cortical and subcortical areas that have been implicated
      in the perception of the own body was less responsive during DP, which might
      point to a specific neural mechanism underlying the 'out-of-body' experience.
      Although the small number of subjects does not allow a generalization of our
      findings, H-DP seems to be a promising tool for the investigation of
      psychological and biological mechanisms of self-inflicted injuries as well as the
      mind-body interplay within the realm of psychosomatic disorders.

PMID- 17230053
TI  - Anger, depression and personality dimensions in patients with migraine without
      aura.
AB  - BACKGROUND: Migraine without aura causes acute and chronic pain and partially
      compromises patients' social functioning and work performance. Over the past
      years, psychiatric comorbidities were frequently observed in these patients,
      together with coping difficulties and typical personality traits. The aim of this
      study was to identify whether migraine patients and controls share distinctive
      personality traits. METHODS: 105 consecutive patients suffering from migraine
      without aura referred to the Headache Center of Turin University were enrolled in
      the study and compared to a control group of 79 healthy subjects. Patients and
      controls completed several psychometric questionnaires, including the Temperament
      and Character Inventory, the Beck Depression Inventory and the State-Trait Anger
      Expression Inventory. RESULTS: Patients suffering from migraine show more
      depressive symptoms, difficult anger management with a tendency to hypercontrol,
      and a distinctive personality profile with high harm avoidance, high persistence
      and low self-directedness. When a logistic regression was performed, the only
      significant predictors of migraine were temperament variables. CONCLUSIONS: The
      results suggest that the personality traits and psychosomatic mechanisms of
      migraine patients may make them vulnerable to stress and less skilled in coping
      with pain. These traits correlate with dysregulated neurotransmitter systems
      which may also be part of the psychobiological components of personality,
      depressive disorders and migraine itself.

PMID- 17230054
TI  - Human skin penetration of sunscreen nanoparticles: in-vitro assessment of a novel
      micronized zinc oxide formulation.
AB  - The extent to which topically applied solid nanoparticles can penetrate the
      stratum corneum and access the underlying viable epidermis and the rest of the
      body is a great potential safety concern. Therefore, human epidermal penetration
      of a novel, transparent, nanoparticulate zinc oxide sunscreen formulation was
      determined using Franz-type diffusion cells, 24-hour exposure and an electron
      microscopy to verify the location of nanoparticles in exposed membranes. Less
      than 0.03% of the applied zinc content penetrated the epidermis (not
      significantly more than the zinc detected in receptor phase following application
      of a placebo formulation). No particles could be detected in the lower stratum
      corneum or viable epidermis by electron microscopy, suggesting that minimal
      nanoparticle penetration occurs through the human epidermis.

PMID- 17230055
TI  - Endogenous phospholipid metabolite containing topical product inhibits
      ultraviolet light-induced inflammation and DNA damage in human skin.
AB  - BACKGROUND: N-palmitoylethanolamine (PEA) and organic osmolytes are endogenous
      components of the human epidermis and are generated from phospholipids in the
      stratum granulosum. PEA has been shown to exert potent antioxidant and anti
      inflammatory activities. The endogenous organic osmolytes such as betaine and
      sarcosine control skin humidity, but have also been shown to inhibit ultraviolet
      (UV) light-induced oxidative stress in keratinocytes. OBJECTIVES: To investigate
      the effect of a PEA- and organic osmolyte-containing topical product (Physiogel
      AI) on the development of UV light-induced erythema, thymine dimer formation and
      p53 tumor suppressor gene activation, as well as intercellular adhesion molecule
      1 (ICAM-1) and Ki67 expression in normal human skin. METHODS: The UV-induced
      erythema was measured by a spectrofluorometric method. Thymine dimers, p53, ICAM
      1 and Ki67 were detected in skin biopsies using immunohistochemistry. RESULTS:
      Physiogel AI cream significantly inhibited the development of UV light-induced
      erythema and thymine dimer formation in normal human skin, but did not alter the
      number of Ki67+ proliferating keratinocytes and the expression of p53 and ICAM-1.
      CONCLUSIONS: Our results suggest that PEA and organic osmolytes might represent a
      new generation of compounds which suppress UV-induced photodamage.

PMID- 17230056
TI  - The peritoneal explant test for evaluating tissue tolerance to mouthrinses.
AB  - The tissue cultures of explants of neonatal rat peritoneum have been demonstrated
      to be a sensitive test for tissue compatibility with wound antiseptics. The
      present study investigated the suitability of this method to assess the relative
      toxicity of mouthrinses to tissue. Mouthrinses containing 0.1% chlorhexidine
      (Chlorhexamed Fluid 0.1%) (A), 0.3% triclosan (Colgate) (B), essential oil in
      ethanolic solution (Listerine) (C), and amine/stannous fluoride (Meridol) (D)
      were tested at use concentration and in dilutions of 10, 1, and 0.1% with
      exposure times of 1, 10, and 30 min, respectively. The mouthrinses (test) and
      Ringer's solutions (control) were applied to opened rat peritoneum. After
      thorough irrigation with Ringer's solution, a piece of peritoneum was removed and
      1 x 1 mm explants were cut. The explants were cultivated with a bovine serum
      culture medium in 24-well plates at 37 degrees C in a CO2 incubator (95% air, 5%
      CO2). After 10 days, the tissue proliferation for the explants was assessed by a
      stereo microscope at 10x magnification after ethanol fixing and hemalaun
      staining. With 24 grafts per test, the proliferation rate was calculated relative
      to a control, which was run for each mouthrinse and concentration/time
      combination. Data were analyzed using ANOVA (SPSS 11.0) and post-hoc paired t
      test. Statistical significance of all correlations was tested by setting the
      significance level at p < 0.05. At most concentrations, D caused significantly
      less tissue damage than A or B. There was no difference between C and A or C and
      B at 100%. However, the toxicity of C was significantly less than A or B at 10,
      1, and 0.1%. C and D behaved similarly except for the 10% (30 min) and the 1% (10
      min) solutions in which C was significantly less toxic. We concluded that the rat
      peritoneum explant test was demonstrated to be a sensitive test to assess the
      relative toxicity of mouthrinses to tissue.

PMID- 17230058
TI  - Chemoreduction for intraocular retinoblastoma in Malaysia.
AB  - In the last decade, chemotherapy in combination with focal therapy
      (chemoreduction) has been increasingly used in intraocular retinoblastoma to
      avoid enucleation and radiotherapy. The aim of this study was to assess the
      feasibility and outcome of chemoreduction in Malaysian children with
      retinoblastoma. This was a prospective study from August 2001 to January 2006.
      Twenty children (25 eyes) were given 4 cycles of chemoreduction, after which the
      response was assessed. Fourteen eyes showed a complete response, 10 eyes showed a
      partial response, and 1 eye had progressive disease. Twelve eyes developed
      progressive disease later, 9 after an initial complete response and 3 after a
      partial response. Overall, progressive disease occurred in 52%. There were 2
      treatment failures, in Reese-Elsworth groups 3 and 4. Both eyes required
      enucleation. One eye in group 5 required second line chemotherapy to achieve a
      complete response. No eyes were irradiated. Five children (25%) defaulted follow
      up, one of whom returned with disseminated disease. In conclusion, 4 cycles of
      chemoreduction achieved a durable complete response in only 12% of eyes.
      Chemoreduction is feasible in Malaysia but requires good patient compliance and
      close follow-up.

PMID- 17230059
TI  - Growth impairment in beta-thalassemia major: the role of trace element deficiency
      and other potential factors.
AB  - A serious problem in thalassemia major is growth impairment for which several
      possible etiologies have been proposed. Sixty-seven patients with thalassemia
      were randomly enrolled into the study, divided into 2 groups with and without
      growth failure and the correlation between growth failure and the following
      parameters was evaluated: age, sex, serum ferritin level, serum zinc and copper
      concentrations, serum copper-zinc ratio, regularity of blood transfusion, and the
      regularity and duration of chelation therapy. Among all studied parameters, only
      age, duration, and type of chelation therapy and age of beginning chelation
      therapy were significantly different between the 2 groups. Binomial multivariate
      logistic regression showed that the only significant independent correlation was
      between age and growth failure. A 1-year increase in age is associated with a
      1.57-fold increase in the risk of growth impairment. The results of this study
      indicated that a temporally cumulative damage to growth-mediating mechanisms
      except those considered here is responsible for growth failure in thalassemia
      major.

PMID- 17230060
TI  - PET for staging in rhabdomyosarcoma: an evaluation of PET as an adjunct to
      current staging tools.
AB  - BACKGROUND: Complete staging of rhabdomyosarcoma is critical to deliver
      appropriate therapy. We evaluated the role of F-fluorodeoxyglucose positron
      emission tomography (PET) in the staging of patients with rhabdomyosarcoma.
      METHODS: Twenty-four patients with rhabdomyosarcoma had a PET scan during staging
      evaluation, before or within 13 days of initiation of therapy. PET was compared
      with computed tomography (CT), magnetic resonance imaging (MRI), bone scan, and
      pathology. RESULTS: Ninety-six sites were evaluated. All patients had positive
      PET scans at the primary site. Thirty-one PET positive sites at primary,
      regional, or distant sites were biopsied. Pathology in all 31 confirmed disease.
      Standardized uptake value for the primary site at diagnosis ranged from 2.4 to
      12.7 (mean 6.4). At 23 sites, CT or MRI was equivocal for the detection of
      regional or distant spread. In these cases, a negative PET helped to exclude
      disease in 21 of 23 patients. PET failed to capture sites of disease visualized
      by CT, MRI, or bone scan at 10 sites. When comparing PET with the final clinical
      determination of disease extent, PET was 77% sensitive and 95% specific.
      CONCLUSIONS: These preliminary data indicate that PET is a useful adjunct in
      staging rhabdomyosarcoma. A prospective study of PET for staging of
      rhabdomyosarcoma is warranted.

PMID- 17230061
TI  - Concurrent Ewing sarcoma family of tumors and fibrous dysplasia: possible
      diagnostic pitfall.
AB  - We present 2 patients with synchronous Ewing sarcoma family of tumors (ESFTs) and
      fibro-osseous lesion in the independent sites, possibly causing misjudgment in
      staging. Each patient showed another activity apart from the primary ESFT lesion
      on gallium and/or thallium scintigraphy at initial presentation. Of note is that
      such lesions showed no obvious radiologic change even though the primary ESFT
      lesions were mildly shrunken during chemotherapy. The biopsies confirmed fibrous
      dysplasia (FD) in the first patient and fibro-osseous lesion, possibly FD in the
      second patient. As far as we know, concurrent ESFT and FD in independent sites
      have never been described. However, this unusual combination emphasized the
      possibility of concurrent FD mimicking metastasis in a patient with malignancy
      and the view that exploratory biopsy should be performed in a critical case to
      make staging. Further investigation will be required about whether the co
      occurrence of ESFD and FD in our patients is coincidence or genetic linkage.

PMID- 17230062
TI  - Pediatric reference values for molecular markers in hemostasis.
AB  - BACKGROUND: The hemostatic system is a developing and changing process relative
      to age. OBJECTIVES: To distinguish the differences in hemostatic parameters
      between children and adults, and to establish the normal range of these
      parameters in children of different age groups. DESIGN/METHODS: Blood was
      obtained from healthy children aged 1 to 18 years (n=70) and adults (n=26).
      Children were categorized into 3 age groups: 1 to 5 years, 6 to 10 years, and 11
      to 18 years. Several coagulation and fibrinolysis parameters were determined.
      RESULTS: Children in all age groups showed no significant difference in mean
      levels of von Willebrand factor antigen and activity, activated partial
      thromboplastin time, fibrinogen, activated factor VII, tissue plasminogen
      activator, plasminogen activator inhibitor-1, and thrombin activatable
      fibrinolysis inhibitor compared with adults. However, children aged 1 to 5 years
      had significantly higher mean values of soluble thrombomodulin (P=0.001),
      prothrombin time (P=0.03), tissue factor (P<0.001), thrombin-antithrombin complex
      (P<0.001), and D-dimer (P=0.009) whereas they had significantly lower mean levels
      of protein C activity (P=0.02) than did adults. CONCLUSIONS: These data indicate
      physiologic differences in the hemostatic system between children and adults and
      should serve as a useful reference guide in interpreting test results for
      children with suspected bleeding disorders.

PMID- 17230063
TI  - Serum leptin levels in patients with childhood immune thrombocytopenic purpura.
AB  - Acute immune thrombocytopenic purpura (ITP) induces thrombocytopenia by means of
      an autoimmune mechanism. Recent studies suggested that T helper immune response
      is responsible for the pathogenesis of chronic ITP. Despite several studies that
      were carried out, we do not have a clue as to what triggers the autoimmunity.
      Leptin is a 16-kd protein secreted from the adipose tissue. Leptin is
      structurally similar to interleukin (IL)-2, IL-6, and IL-15. The structural
      similarities between leptin receptor and hematopoietic cytokine receptors
      suggested that leptin could play a role in hematopoiesis and immune function.
      Recent studies suggested that leptin could play an important role in
      autoimmunity. We made a prospective analysis of a series of 39 newly diagnosed
      acute childhood ITP in a year period. Serum leptin levels were obtained after
      diagnosis and before treatment and all patients were followed up at least 6
      months to designate acute or chronic event. We conclude that in childhood acute
      ITP, leptin did not play a role in the pathophysiology of the disease. Further
      investigations are needed to examine what triggers T cells and how the autoimmune
      disease became.

PMID- 17230064
TI  - Ethnic differences in the frequency of subtypes of childhood acute lymphoblastic
      leukemia: results of the Malaysia-Singapore Leukemia Study Group.
AB  - Childhood acute lymphoblastic leukemia (ALL) is clinically heterogeneous with
      prognostically and biologically distinct subtypes. Although racial differences in
      frequency of different types of childhood ALL have been reported, many are
      confounded by selected or limited population samples. The Malaysia-Singapore (MA
      SPORE) Leukemia Study Group provided a unique platform for the study of the
      frequency of major subgroups of childhood ALL in a large cohort of unselected
      multiethnic Asian children. Screening for the prognostically important chromosome
      abnormalities (TEL-AML1, BCR-ABL, E2A-PBX1, and MLL) using multiplex reverse
      transcription polymerase chain reaction was performed on 299 consecutive patients
      with ALL at 3 study centers (236 de novo, 63 at relapse), with the ethnic
      composition predominantly Chinese (51.8%) and Malay (34.8%). Reverse
      transcription polymerase chain reaction was successful in 278 (93%) of cases
      screened. The commonest fusion transcript was TEL-AML1 (19.1%) followed by BCR
      ABL (7.8%), MLL rearrangements (4.2%), and E2A-PBX1 (3.1%). Chinese have a
      significantly lower frequency of TEL-AML1 (13.3% in de novo patients) compared
      with Malays (22.2%) and Indians (21.7%) (P=0.04). Malays have a lower frequency
      of T-ALL (6.2%) compared with the Chinese and Indians (9.8%). Both Malays (7.4%)
      and Chinese (5.0%) have significantly higher frequency of BCR-ABL compared with
      the Indian population (P<0.05) despite a similar median age at presentation. Our
      study suggests that there are indeed significant and important racial differences
      in the frequency of subtypes of childhood ALL. Comprehensive subgrouping of
      childhood ALL may reveal interesting population frequency differences of the
      various subtypes, their risk factors and hopefully, its etiology.

PMID- 17230065
TI  - A strategy for controlling potential interactions between natural health products
      and chemotherapy: a review in pediatric oncology.
AB  - The high prevalence of complementary and alternative medicine use including
      natural health products (NHPs) in the pediatric oncology population is well
      established. The potential for concurrent use of NHPs with conventional
      chemotherapy necessitates physician awareness regarding the potential risks and
      benefits that might come from this coadministration. Knowledge of interactions
      between NHPs and chemotherapy is poorly characterized; however, an understanding
      of potential mechanisms of interaction by researchers and clinicians is
      important. Concerns regarding the use of antioxidants during chemotherapy are
      controversial and evidence exists to support both adherents and detractors in
      this debate. Our review addresses issues regarding potential interactions between
      NHPs and chemotherapies used in pediatric oncology from a pharmacokinetic and
      pharmacodynamic perspective. Examples of combinations of NHP and chemotherapies
      are briefly presented in addition to a strategy to avoid (or induce) a possible
      interaction between a NHP and chemotherapy. In conclusion, more clinical research
      is needed to substantiate or preclude the use of NHPs in the treatment of cancer
      and especially in combination with chemotherapy.

PMID- 17230066
TI  - Early lymphocyte recovery as a prognostic indicator for high-risk Ewing sarcoma.
AB  - BACKGROUND: Increasing evidence suggests that lymphocyte recovery plays a major
      part in tumor control. Facilitating immune reconstitution might be a novel
      direction of cancer therapy. The purpose of this study was to determine if early
      lymphocyte recovery is an independent prognostic indicator for high-risk Ewing
      sarcoma outcome. RESULTS: Data of 24 Ewing sarcoma patients were analyzed (age, 3
      to 50 y; median, 16.5; male to female, 16:8). The 5-year overall survival (OS) of
      the total population was 47.9% [10.6 standard error (SE)]. Patients were
      separated into 2 groups: prolonged lymphopenia versus early lymphocyte recovery,
      using a threshold absolute lymphocyte count (ALC) of > or =500 cells/microL on
      day 15. The majority (67%; n=16) of the patients had an ALC > or =500
      cells/microL, and of these 10/16 are alive with a 5-year OS of 58.7% (13.2 SE).
      In contrast, 33% (n=8) of patients had an ALC <500 cells/microL on day 15 and
      only 2/8 are alive with a 5-year OS of 25% (15.3 SE). This difference was
      significant (P=0.007 using the log rank test). When comparing patients with
      metastatic disease, patients with an ALC-15 < 500 cells/microL had a median
      survival of 13 months, whereas patients with an ALC-15 > or =500 cells/microL had
      a median survival of 29.5 months. All patients had an ALC before chemotherapy of
      >1000 cells/microL. The difference was significant (P value=0.001 using the log
      rank test). Univariate analysis of platelet counts, age, sex, and absolute
      neutrophil count showed no statistically significant association with OS.
      CONCLUSIONS: The data demonstrate that an ALC > or =500 cells/microL on day 15 of
      the first course of chemotherapy is an independent prognostic factor associated
      with superior OS in high-risk Ewing sarcoma.

PMID- 17230067
TI  - Trilateral retinoblastoma with suprasellar tumor and associated pineal cyst.
AB  - Trilateral retinoblastoma (TRb) is a well-known syndrome associating hereditary
      retinoblastoma (Rb) with an intracranial neuroblastic tumor arising usually in
      the pineal region, rarely at the suprasellar or parasellar site. It develops in
      most cases after diagnosis of Rb. The outcome is usually fatal because of
      secondary spinal dissemination. Pineal cysts have recently been reported as a
      benign variant of TRb. We report the unusual presentation of a TRb in a 12-month
      old boy with extensive bilateral Rb, a voluminous suprasellar tumor, pineal cyst,
      and leptomeningeal disease. The special features of this "quadrilateral" Rb are
      discussed.

PMID- 17230068
TI  - Matched unrelated bone marrow transplantation without splenectomy for a child
      with Gaucher disease caused by homozygosity of the L444P mutation, who also
      suffered from schizencephaly.
AB  - Splenectomy followed by bone marrow transplantation (BMT) has been applied
      successfully in the treatment of neuronopathic Gaucher disease (GD). GD in
      combination with schizencephaly has not previously been reported. We describe a
      girl who presented with hemiparesis and oculomotor apraxia since infancy, and
      thereafter developed progressive anemia, thrombocytopenia, hepatosplenomegaly,
      psychomotor retardation, and skeletal abnormalities. GD caused by homozygosity of
      the L444P mutation was diagnosed, in combination with schizencephaly. The child
      received enzyme replacement therapy for 3 years, followed by successful matched
      unrelated BMT without splenectomy. The strategy of BMT without splenectomy after
      a period of enzyme replacement may be feasible in neuronopathic GD.

PMID- 17230069
TI  - A case of Langerhans cell histiocytosis presented with pneumothorax.
AB  - Pneumothorax (PTX) is an unusual complication of Langerhans cell histiocytosis
      (LCH) in childhood. Spontaneous PTX is rare in childhood, and it is very rare in
      infancy. There are no specific recommendations for the treatment of PTX from LCH
      described in the literature. We are presenting a 19-month-old boy, who suddenly
      developed left-sided PTX with infiltrations in both lungs. He presented with PTX
      and skin lesions. He had a prolonged cardiac arrest, and although resuscitation
      was successful he required continuing ventilatory support (intermittent positive
      pressure ventilation). Because he suddenly developed right-sided PTX and died on
      the second day of the admission, his LCH diagnosis was made only postmortem. So,
      he did not receive chemotherapy. It is likely that intermittent positive-pressure
      ventilation during the operation induced the development of much more multiple
      lung bullae, which subsequently ruptured, and/or it facilitated the development
      of the right-sided PTX. The patients with PTX and skin lesions, including babies,
      most likely have LCH and specific chemotherapy should be started in emergency,
      even before the final diagnosis is achieved.

PMID- 17230070
TI  - Undifferentiated (embryonal) sarcoma of the liver complicated with rupture in a
      child.
AB  - Undifferentiated (embryonal) sarcoma of the liver (UESL) is a rare hepatic tumor
      and mainly occurs in children. It usually has cystic changes on computed
      tomography scan, which represents areas of necrosis and hemorrhages. UESL is a
      rapidly growing tumor and tumor rupture does occur. We reported a girl with a
      large multicystic hepatic tumor who died of tumor rupture shortly after the
      diagnosis of UESL. It is mandatory to be aware of this potentially fatal
      complication especially in patients with UESL of large tumor volume.

PMID- 17230071
TI  - Pseudotumor cerebri after allogeneic bone marrow transplant associated with
      cyclosporine a use for graft-versus-host disease prophylaxis.
AB  - Pseudotumor cerebri (PTC) is a syndrome of increased intracranial pressure for
      which several risk factors have been described. We report 2 patients who
      developed PTC after cyclosporine A (CsA) therapy for graft-versus-host disease
      (GvHD) prevention after bone marrow transplant. Both patients were obese which
      may have also contributed to the PTC. Cessation of CsA and combinations of
      mycophenolate mofetil or tacrolimus and systemic steroids and/or acetazoleamide
      were effective in managing the symptoms, improving the ocular complications and
      keeping GvHD asymptomatic. These cases suggest that induction of PTC by CsA used
      for GvHD prophylaxis in patients undergoing bone marrow transplant is not rare.
      Physicians who are following patients on CsA need to be alert to the possibility
      of PTC. Prompt diagnosis followed by thorough evaluation and treatment are
      crucial for preventing visual loss and improving associated symptoms.

PMID- 17230072
TI  - 18F-fluorodeoxyglucose-positron emission tomography in the characterization of
      suspected rhabdoid renal tumor recurrence: a case report.
AB  - Rhabdoid tumor is a rare, aggressive, and undifferentiated cancer, that can be
      localized in the central nervous system, in the thorax or in the kidney. 18F
      fluorodeoxyglucose-positron emission tomography (FDG-PET) is a noninvasive
      technique in cancer patients' management. Its role in the diagnosis and staging
      of rhabdoid renal tumor is not known at all. We report the case of a child with
      suspected recurrence of rhabdoid renal tumor studied with FDG-PET/computed
      tomography. A 4-year-old male previously treated for a rhabdoid tumor of the left
      kidney, underwent PET scan to differentiate local recurrence from postsurgical
      fibrosis. FDG-PET study showed the presence of intense, multiple, and
      inhomogeneous tracer uptakes in the left renal fossa (ie, the site of suspected
      computed tomography recurrence), with the involvement of the adjacent abdominal
      wall. Further pathologic uptakes were evidenced in the para-aortic, celiac,
      mesenteric areas, and at the hepatic hilum. Therefore, PET scan allowed a
      complete disease staging, evidencing unexpected local and distant disease
      extension. Thus, FDG-PET study could be considered in the evaluation of patients
      with renal rhabdoid tumor, at least when disease recurrence is suspected.

PMID- 17230073
TI  - Systemic juvenile xanthogranulomatosis imitating a malignant abdominal wall tumor
      with lung metastases.
AB  - Juvenile xanthogranulomatosis (JXG) is a rare benign condition, which usually
      presents with characteristic skin lesions and can be diagnosed clinically.
      However, systemic JXG may involve a wide range of extracutaneous sites and may
      pose a diagnostic dilemma for the clinician, radiologist, and pathologist. In
      particular it may simulate malignancy. Here, we report a case of systemic JXG
      within the abdominal wall musculature and lungs, which imitated a sarcoma with
      pulmonary metastases on computerized tomography. To the best of our knowledge,
      this is the first such reported case. In particular, systemic disease presenting
      without skin lesions is unusual.

PMID- 17230074
TI  - Combined B12 and iron deficiency in a child breast-fed by a vegetarian mother.

PMID- 17230075
TI  - Microvascular surgery.
AB  - LEARNING OBJECTIVES: After reading this article, the participant should be able
      to: 1. Describe the common room set-up, medical considerations, and technical
      equipment necessary to perform microvascular surgery. 2. Describe the common
      arterial and venous techniques in performing microvascular surgery. 3. Recognize
      the common flap types along with their vascular supply and innervation used for
      microvascular surgery. 4. Describe common techniques for flap monitoring. 5.
      Describe techniques and medications for thrombolytic therapy. 6. Describe common
      medical conditions that may preclude an optimal result in microvascular surgery.
      SUMMARY: This article will explore common approaches to microsurgery. It is
      anticipated that the readers can utilize this article for maintenance of
      certification educational components and take the principles outlined and apply
      them to their daily practice.

PMID- 17230076
TI  - A prospective assessment of surgical risk factors in 400 cases of skin-sparing
      mastectomy and immediate breast reconstruction with implants to establish
      selection criteria.
AB  - BACKGROUND: Although attempts have been made to identify the risk factors leading
      to complications after combined skin-sparing mastectomy and immediate prosthetic
      breast reconstruction, hardly any criteria are available to preoperatively
      distinguish patients in whom such an eventful postoperative course may be
      expected. Therefore, the authors wanted to establish which factors increase the
      risk of surgical complications to such a level as to adjust their indications for
      immediate breast reconstruction after skin-sparing mastectomy. METHODS: The
      authors prospectively studied the clinical relevance of six patient-related and
      nine procedure-related characteristics as potential risk factors for a
      complicated surgical outcome in 400 combined procedures in 309 patients by
      univariate and multivariate logistic regression analysis. Risk factors that
      proved significantly correlated with loss of implant by both analyses were
      accepted as clinical selection criteria that distinguish potential candidates
      with an unacceptably high risk of such loss. RESULTS: Mild complications occurred
      significantly more often in patients who were older than the mean age of 43 years
      and in breasts that were more than average sized or operated on by a fellow in
      oncologic surgery. Implants were lost significantly more often in patients who
      were obese or smoked and in breasts that were more than average sized.
      CONCLUSIONS: The clinically relevant increase of risk of implant loss should lead
      to reluctance to perform combined skin-sparing mastectomy and immediate
      prosthetic breast reconstruction in obese patients who smoke (32 percent loss)
      and in those with more than average sized breasts (27 percent loss).

PMID- 17230077
TI  - Breast reconstruction following mastectomy for breast cancer: the decisions of
      sexual minority women.
AB  - BACKGROUND: Prior research on decision-making for reconstructive surgery after
      mastectomy has not addressed the specific considerations of sexual minority women
      (women who partner with women, and lesbian or bisexual identified women). The
      purpose of this study is to explore which issues sexual minority women considered
      when making decisions on reconstructive surgery and to understand the influence
      and perspectives of these women's most important support persons. METHODS: Study
      participants were recruited through targeted community-based sampling. The
      authors conducted individual semistructured interviews with 15 sexual minority
      women who had been treated with mastectomy after breast cancer diagnosis and 12
      support persons who were identified by these women as their most important source
      of support. Using qualitative data analysis software, transcribed interviews were
      analyzed. Through constant comparison methods, themes related to the decision on
      and experiences and satisfaction with reconstructive choice were identified from
      the narrative data. RESULTS: The considerations of women who decided for or
      against reconstruction are rooted in a value system and body image shaped by
      their sexual minority identity. Women who chose reconstruction experienced
      difficulties and regrets, whereas women without reconstruction adjusted well
      after time. Partners of sexual minority women matched the level of satisfaction
      with reconstructive choice achieved by the women themselves. CONCLUSION:
      Providers who treat sexual minority women might benefit from knowing about issues
      important to this population to provide more comprehensive care.

PMID- 17230078
TI  - The double opposing periareola flap: a novel concept for nipple-areola
      reconstruction.
AB  - BACKGROUND: This report describes the authors' currently favored method of nipple
      reconstruction that has been developed and used by the senior author over the
      past 26 months. METHODS: A pull-out flap is derived as the lead edge of one of
      two opposing skin flaps contained in a circular design approximating the areola
      complex of the opposite breast. The larger flap gives rise to the nipple
      construct, a derivative of the skate flap design. The flap donor areas are closed
      by suture approximation centrally and peripherally within the areolar margins.
      The donor area resulting from elevating the central flaps that give rise to the
      nipple is closed by direct suturing; the opposing subcutaneous dermal pedicle
      flaps are advanced or "slid" toward each other centrally, and the peripheral area
      is closed by a purse-string suture placed in the periareolar incision. The only
      undermined area is the nipple flap itself. There is no undermining of the larger
      flaps or peripheral breast skin. The dissection is straightforward and the
      technique is rapid. RESULTS: The procedure was used 47 times in 36 patients
      (unilateral reconstruction, 25 patients; bilateral reconstruction, 11 patients),
      with no flap losses or wound separations. In one case of redo bilateral nipple
      reconstruction, ischemia noted at the most anterior aspect (distal portion) of
      both flaps healed with the application of topical ointment. CONCLUSIONS: This
      novel design for nipple-areola complex reconstruction can be used in either
      primary or secondary nipple reconstruction. Of particular advantage, all of the
      scars are contained within the peripheral periareolar incision and thus can be
      completely camouflaged by an intradermal tattoo. Nipple projection has been
      consistently maintained and appears similar to that of a skate flap.

PMID- 17230079
TI  - Symptoms and related severity experienced by women with breast hypertrophy.
AB  - BACKGROUND: Breast hypertrophy is a common condition that can be associated with
      significant morbidity. Symptoms emphasized in the literature include physical
      problems such as pain, intertrigo, and exercise restrictions. The purpose of this
      study was to explore the suffering experienced by women with breast hypertrophy
      and to evaluate the importance of different symptoms. METHODS: Twenty-one women
      with breast hypertrophy were divided into five focus groups guided by a
      facilitator. Open discussion was encouraged to generate a comprehensive list of
      symptoms experienced by women with breast hypertrophy. Subjects then completed an
      iterative process to determine the relative importance of each symptom.
      Conversations were recorded, transcribed, and analyzed using Nvivo software.
      RESULTS: A weighted list of 45 dominant symptoms was created from an initial pool
      of 128. Physical pain symptoms predominated in the older age group, whereas
      younger women expressed more psychological symptoms. Difficulties experienced by
      these women transcended all aspects of their lives. Back, neck, and shoulder pain
      were considered most troublesome, followed by exercise difficulties, poor
      posture, and low self-esteem. CONCLUSIONS: This study provides insight into the
      burden of breast hypertrophy and has implications for the objective assessment of
      this condition in the clinical setting.

PMID- 17230080
TI  - Reliability and validity testing of the Patient and Observer Scar Assessment
      Scale in evaluating linear scars after breast cancer surgery.
AB  - BACKGROUND: The Patient and Observer Scar Assessment Scale is a promising new
      method incorporating observer and patient ratings in evaluating burn scars. The
      authors compared this tool to the Vancouver Scar Scale in a cohort of women with
      linear scars from breast cancer surgery. METHODS: Twenty women with newly
      diagnosed breast cancer were prospectively accrued. Thirty-one scars were
      evaluated. The median time from surgery to scar assessment was 8 weeks (range, 3
      to 25 weeks). Observer assessment was performed by three independent raters using
      the Vancouver scale and the observer component of the new tool. Patient self
      assessment was performed using the patient component of the tool. Internal
      consistency, interobserver reliability, and convergent validity were examined.
      RESULTS: Internal consistency was acceptable for the Vancouver scale and both
      components of the new tool (Cronbach's alpha, 0.71, 0.74, and 0.77,
      respectively). Interobserver reliability was substantial with both the Vancouver
      scale and the observer tool (average measure intraclass coefficient correlation,
      0.78 and 0.60, respectively). The observer tool and Vancouver scale correlated
      significantly with each other (p < 0.001), but only the observer tool correlated
      well with patients' ratings (p = 0.04). CONCLUSIONS: In surgical scar assessment,
      the new Patient and Observer Scar Assessment Scale and Vancouver Scar Scale were
      both associated with acceptable internal consistency and interobserver
      reliability. The new tool is more comprehensive and has higher correlation with
      patients' ratings. These findings support the use of the new tool as a reliable,
      valid, and comprehensive approach to assess linear surgical scars.

PMID- 17230081
TI  - Cultured autologous keratinocytes in suspension accelerate epithelial maturation
      in an in vivo wound model as measured by surface electrical capacitance.
AB  - BACKGROUND: Human epidermis serves as a protective covering against loss of
      endogenous fluids and exogenous microbial invasion. Cultured epithelial autograft
      suspensions have been used to enhance epithelialization to improve mortality,
      morbidity, and the overall quality of the scar. The measurement of surface
      electrical capacitance as an indicator of transepidermal water loss has been used
      in neonatology and dermatology to determine epidermal maturation. This tool has
      been used in a double-blind, randomized, controlled trial to compare the effects
      of cultured epithelial autograft in suspension on epidermal healing and
      maturation compared with a control in an in vivo partial thickness wound model.
      METHODS: In this double-blind, randomized, controlled trial (n = 8), the authors
      assessed the effect of cultured epithelial autograft on epidermal healing and
      maturation in standardized partial thickness wounds. Surface electrical
      capacitance was compared on 16 split-thickness skin graft donor sites treated
      with cultured epithelial autograft (n = 8) against controls treated with
      Dulbecco's Modified Eagle's Medium (n = 8) using a NOVA Dermaphase Meter at 4, 5,
      6, and 7 days postoperatively. RESULTS: A statistically significant difference on
      continuous readings at days 5 (p = 0.012) and 7 (p = 0.036) and instantaneously
      on days 5 (p = 0.025) and 6 (p = 0.036) in surface electrical capacitance was
      observed in the cultured epithelial autograft over the Dulbecco's Modified
      Eagle's Medium-treated wounds. CONCLUSIONS: Measuring surface electrical
      capacitance provides an objective and repeatable method of assessing epidermal
      maturation. This study indicates that the rate of epithelialization and epidermal
      maturation is more rapid in partial thickness epidermal skin wounds treated with
      cultured epithelial autograft.

PMID- 17230082
TI  - Transplantation of osteoblast-like cells to the distracted callus in the rabbit
      mandible.
AB  - BACKGROUND: The purpose of this study was to investigate whether injections of
      marrow-derived mesenchymal progenitor cells could be used to facilitate new bone
      formation during distraction osteogenesis. METHODS: Fifteen New Zealand rabbits
      underwent bilateral osteotomy. After a 1-week latency period, bone distraction
      was activated at a rate of 2.0 mm/day for 5 days. The marrow-derived mesenchymal
      progenitor cells derived from the ilium marrow were cultured to a population of
      10 in 0.5 ml and then unilaterally transplanted to the gap of distracted callus
      immediately after distraction had been terminated. Rabbits were killed at 2, 4,
      and 6 weeks after completion of bone lengthening. The distracted areas were
      harvested and evaluated by histologic, histomorphometric, radiographic, and
      scanning electron microscopic analysis. Bone mineral density in the lengthened
      callus was evaluated using dual-energy x-ray absorptiometry. RESULTS:
      Radiographic evaluation indicated a significant increase in bony union of the
      distraction regenerate in the experimental side compared with the control side.
      Corresponding to the radiographic findings, the histologic examination showed an
      earlier and more intensive bone formation in the experimental side after 2, 4,
      and 6 weeks compared with the control side. Larger chondroid islands were found
      evident in distracted bone of the control side than in the experimental side.
      CONCLUSIONS: The results show that transplantation of osteoblast-like cells
      promotes maturity of the distracted callus, as observed on the second and fourth
      weeks after lengthening. The method appears promising as a means of shortening
      the consolidation period of osteodistraction and decreasing complications during
      bone lengthening.

PMID- 17230083
TI  - Operating curves to characterize the contraction of fibroblast-seeded collagen
      gel/collagen fiber composite biomaterials: effect of fiber mass.
AB  - BACKGROUND: Collagen is a well-established and important biomaterial that could
      be used to help meet significant medical needs for various soft-tissue
      replacements. Many efforts to create engineered soft-tissue constructs by seeding
      cells within collagen gels have been hampered because constituent cells contract
      collagen gels over time, resulting in a construct that is only a fraction of the
      original size and that contains a cell population that has suffered a large
      degree of cell death. However, the presence of embedded short collagen fibers has
      been shown to significantly limit contraction and dramatically enhance
      permeability in fibroblast-seeded collagen gels. METHODS: Five volume fractions
      of short collagen fibers were embedded in fibroblast-seeded collagen gels.
      Collagen gel contraction (n > or = 4 for all groups) and cell viability (n > or =
      3 for all groups) were examined after up to 2 weeks in culture. RESULTS: The
      present study demonstrated that increasing the volume fraction of short collagen
      fibers in fibroblast-seeded collagen gels correspondingly reduced the amount of
      gel contraction without negatively impacting cell viability after 2 weeks of
      culture. Furthermore, operating curves that describe the quantitative
      relationships between the contraction of fibroblast-seeded collagen gel/collagen
      fiber composite biomaterials, time in culture, and volume fraction of embedded
      fibers were obtained. CONCLUSION: The resulting operating curves enable
      investigators to tailor initial fabrication procedures to ultimately yield cell
      seeded collagen composites of specifically desired sizes-a critical step toward
      developing clinically useful engineered soft-tissue constructs.

PMID- 17230084
TI  - Electrically stimulated rectus abdominis muscle flap to achieve enterostomal
      continence: development of a functional canine model.
AB  - BACKGROUND: Dynamic myoplasty has many clinical applications and has proven to be
      a versatile surgical procedure with great promise. This procedure has been used
      to achieve fecal/urinary continence, as in the dynamic graciloplasty, and to
      augment cardiac ventricular function, as is commonly seen with dynamic latissimus
      cardiomyoplasty. In the present study, the authors describe a functional
      innovative island flap sphincter created from the rectus abdominis muscle in a
      large-animal model to provide stomal continence for future clinical studies.
      METHODS: The caudal region of the rectus abdominis muscle in eight mongrel
      canines (23 to 25 kg) was investigated through anatomical dissections during
      which the location of the neurovascular pedicles and the intersegmental muscle
      dimensions between the muscle inscriptions were noted. The rectus abdominis
      muscle was used to create functional dynamic stomal sphincters that were trained
      with subcutaneously implanted pulse stimulators. RESULTS: The neurovascular
      pedicles were consistently found in similar locations along the posterior medial
      aspect of the caudal portion of the canine's rectus abdominis muscle. The
      vertical height of the deep inferior epigastric pedicle and caudal intercostal
      nerve muscular mean entry points were 6.75 +/- 1.89 cm and 7.44 +/- 0.86 cm,
      respectively. The mean caudal intersegmental muscle length of the rectus
      abdominis muscle used to create the sphincter was 9.69 +/- 1.81 cm. CONCLUSIONS:
      The canine rectus abdominis muscle has reliable anatomical locations where the
      neurovascular pedicle may be found. This canine muscle may be used to create a
      continent island flap stomal sphincter. This large-animal sphincter model is
      versatile, durable, and easy to manipulate, with minimal morbidity to the animal.

PMID- 17230085
TI  - The Rho-associated kinase inhibitor fasudil hydrochloride enhances neural
      regeneration after axotomy in the peripheral nervous system.
AB  - BACKGROUND: The Rho family of small GTPases is responsible for various processes
      involving actin cytoskeleton in eukaryotic cells, including neurite outgrowth.
      Several substances found at the peripheral nerve injury site were shown to
      activate one member of this family, Rho. The activation of Rho leads to neurite
      outgrowth inhibition and the development of posttraumatic neuropathic pain. The
      authors used the clinically tested Rho-associated kinase inhibitor fasudil
      hydrochloride to enhance the functional recovery of the peripheral nerve in the
      rat. METHODS: In the peroneal nerve interpositional graft model, the authors
      administered fasudil (experimental groups) or saline (control groups) (1)
      intraperitoneally and (2) directly into the graft by microinjection (n = 6
      animals per experimental condition). Neural recovery was assessed during
      postoperative follow-up lasting 80 days by peroneal functional index,
      electrophysiologic, and histomorphometric analyses. RESULTS: The peroneal
      functional index returned to values not significantly different from preoperative
      values on days 55 (fasudil injected into the graft) and 60 (fasudil injected
      intraperitoneally) in the experimental groups. In the control groups, this took
      70 (saline injected intraperitoneally) and 75 days (saline injected into the
      graft). These results are supported by electrophysiologic and histomorphologic
      assessments. CONCLUSIONS: The authors determined that fasudil hydrochloride was
      capable of accelerating the functional regeneration after peripheral nerve
      axotomy, which is consistent with the results of reports about Rho cascade
      disruption in the central nervous system. Because fasudil hydrochloride is a
      clinically tested drug, it could be used to enhance neural regeneration in human
      patients as well.

PMID- 17230086
TI  - Medial canthal reconstruction with glabellar combined Rintala flaps.
AB  - BACKGROUND: In medial canthal reconstruction, the continuity of color and texture
      and the reproduction of natural external appearance are required, and
      reconstruction with a flap adjacent to the defect is frequently performed as the
      first choice. The authors have performed reconstruction with a glabellar flap
      combined with a Rintala flap in five patients. METHODS: A glabellar flap, which
      is rectangular according to the unit principle, was elevated, and after thinning
      and trimming to the defect shape, was transferred to the medial canthal defect.
      The donor site of the glabellar flap was closed with a Rintala flap. RESULTS:
      Reconstruction by means of this procedure was performed in five patients with
      defects after resection of medial canthal basal cell carcinoma. In one patient
      with extension of the defect to the upper and lower eyelids, the tip of the
      glabellar flap was divided into two portions and transferred to the defective
      site. No recurrence was observed in any patient, and satisfactory results
      including aesthetic results were obtained in all patients. CONCLUSIONS: This
      technique can be performed readily and is applicable to the reconstruction of
      relatively large defects and is also aesthetically excellent because of a
      postoperative suture line that is consistent with the topographic curve. This
      technique may be useful for medial canthal reconstruction.

PMID- 17230087
TI  - Maxillary and mandibular reconstruction using bicortical calvarial bone grafts: a
      retrospective study of 122 reconstructions in 73 patients.
AB  - BACKGROUND: Using classic maxillary and mandibular reconstruction with mandibular
      bone grafts or unicortical calvarial bone grafts, the authors performed 122
      reconstructions in 73 patients using bicortical calvarial bone grafts and report
      the results in this article. Such a technique has not been previously described
      in the world literature. METHODS: Seventy-three patients, 55 women and 18 men,
      with severely atrophied maxillas or mandibles were treated with bicortical
      calvarial bone grafts and placement of implants over a 5-year period. Patient
      selection was based on the important insufficient remaining height or width of
      bone placement of multiple 10-mm implants and the thinness of the calvaria (<5
      mm). All patients had major bone atrophy. RESULTS: Twenty-nine patients had 121
      implants placed in vertical bicortical bone grafts and 40 patients had 170
      implants placed in horizontal bicortical bone grafts. All patients underwent a
      two-stage procedure, with the implants being placed 4 to 5 months after the
      grafting procedure. The majority of maxillary implants were placed between the
      canine eminence and zygomatic buttress. Of the 122 bicortical calvarial bone
      grafts that took, two cases presented an incised wound of the dura. A simple
      nonabsorbable suture was performed in these two cases without any postoperative
      problems. There were no cerebral injuries encountered with the donor sites.
      CONCLUSIONS: Bicortical bone grafting seems to be a solution for reconstruction
      of voluminous bone atrophy in cases of thin calvaria. Because of legal issues,
      such a technique must be performed by a trained craniofacial surgery team. The
      resorption rate seems to be lower in cases of bicortical bone graft.

PMID- 17230089
TI  - Turnover flap closure of recalcitrant tracheostomy fistula: a simplified
      approach.
AB  - BACKGROUND: Chronic and nonclosing tracheostomy fistula can often significantly
      impair quality of life, vocalization, and local hygiene. Although many of these
      fistulas close on their own after decannulation or after local debridement, a
      significant percentage do not and require flap closure. In this article, the
      authors present their experience with a multilayered flap closure technique that
      has proven reliable, quick, and extremely easy to perform, even in recalcitrant
      cases. METHODS: A medially based turnover skin flap closes the tracheal defect
      without tension and does not narrow the lumen. Double and layered local muscular
      coverage provides healthy soft-tissue coverage and eliminates a tethered and
      depressed scar appearance. Skin closure respects relaxed tension lines. RESULTS:
      Six patients with recalcitrant tracheostomy fistula have to date undergone this
      repair without recurrence, and cosmesis has been excellent. CONCLUSIONS:
      Complicated and recurrent tracheal fistulas are successfully treated with a
      tension-free, multilayered flap reconstruction; the design incorporates
      fundamental aesthetic and reconstructive principles.

PMID- 17230090
TI  - Objective assessment of keloid scars with three-dimensional imaging: quantifying
      response to intralesional steroid therapy.
AB  - BACKGROUND: Treatment of keloid scars poses a significant challenge. Assessment
      of treatment response and research in this area depend on the availability of
      objective, accurate, and reproducible outcome measures. At present, scars are
      assessed using subjective grading systems, or with cumbersome investigations such
      as direct casting. The authors assessed the feasibility of objectively monitoring
      response to intralesional steroid treatment in routine clinical practice with
      quantitative three-dimensional imaging. METHODS: Scar volume was quantified using
      a validated three-dimensional speckle-pattern stereophotogrammetry before and for
      a minimum of 8 weeks after intralesional steroid therapy in 12 patients with
      keloid scars. RESULTS: Mean scar volume at the start of treatment was 0.73 +/-
      0.701 cc (range, 0.12 to 2.15 cc); this was reduced to 0.14 +/- 0.302 cc (range,
      0.007 to 1.08 cc) after monthly intralesional injections of triamcinolone acetate
      (p < 0.001; analysis of variance). The majority of patients achieved a greater
      than 50 percent response within 8 weeks of the start of therapy, but poor
      treatment response was noted and quantified in a minority of patients.
      CONCLUSIONS: Three-dimensional stereophotogrammetry is a rapid and noninvasive
      method of scar volume assessment that could allow accurate and objective
      monitoring of treatment response to be incorporated into clinical practice.
      Therefore, it can be of considerable value in assessing treatment efficacy and
      evaluating new therapeutic strategies.

PMID- 17230091
TI  - Axillary hyperhidrosis: a 5-year review of treatment efficacy and recurrence
      rates using a new arthroscopic shaver technique.
AB  - BACKGROUND: Axillary hyperhidrosis is a chronic condition characterized by excess
      axillary perspiration. This results in considerable patient morbidity, with no
      consistently efficacious medical or surgical treatment method described in the
      literature. METHODS: All cases of axillary hyperhidrosis over a 5-year period
      were reviewed retrospectively. Data were gathered by a chart review and telephone
      interview. Inclusion criteria included primary hyperhidrosis, failed conservative
      therapy, no prior surgical therapy, surgical management using a new arthroscopic
      shaver technique (R.L.B.-S.), and 6 months of postoperative follow-up. The
      technique used was consistent between surgeons. Sweating severity was assessed
      using a subjective numerical rating scale ranging from 1 to 10. Patient
      demographics, symptom history, results, and complications were analyzed. RESULTS:
      Average follow-up for 50 patients meeting the inclusion criteria was 28 months.
      The subjective severity scale demonstrated severity of 9.8 of 10 preoperatively
      and 2.3 of 10 postoperatively. Three patients (6 percent) reported mild
      recurrence of symptoms (4.6 of 10), which was not severe enough to seek further
      treatment. The average follow-up of those patients was 18.5 months. An overall
      subjective satisfaction of 96 percent was found, with a treatment success rate of
      94 percent. Complications were minimal and self-limiting. The average time away
      from employment was 3.9 days and the average surgical operating room time was 46
      minutes. CONCLUSIONS: The authors' new arthroscopic shaver technique is
      efficacious, with no significant morbidity, a 96 percent satisfaction rate, a
      subjectively measured 75 percent reduction of sweat, and a recurrence rate of
      only 6 percent. For cases of primary hyperhidrosis affecting the axilla not
      amenable to conservative treatment, the authors recommend an arthroscopic shaver
      technique as the first-line treatment of choice.

PMID- 17230092
TI  - The utility of deep soft-tissue cultures in diagnosing the causative agent of
      sternal osteomyelitis following median sternotomy.
AB  - BACKGROUND: The authors' goal was to determine whether the bacteria cultured from
      the mediastinal deep soft tissues matched those identified by the sternal bone
      cultures in cases of mediastinitis with clinically suspected sternal
      osteomyelitis, in hopes of eliminating the need for sternal bone biopsy. METHODS:
      The authors retrospectively reviewed the charts of 27 Detroit Medical Center
      patients who underwent median sternotomy and developed mediastinitis with
      clinical suspicion of osteomyelitis between 1996 and 2004. RESULTS: Although only
      18 of 27 of the authors' patients had positive bone cultures, they demonstrate
      that in 94 percent (17 of 18) of these patients, the organisms cultured from the
      mediastinal deep soft-tissue cultures matched those cultured from the positive
      sternal bone cultures. CONCLUSIONS: With the results obtained from this study,
      the authors hope to promote a less-invasive means of investigating osteomyelitis
      in sternal wounds, to prevent the complications associated with obtaining a bone
      biopsy specimen in a contaminated soft-tissue setting. Instead, the authors
      suggest thoracic computed tomographic scanning as a noninvasive means of
      clinically demonstrating osteomyelitis of the sternum, and culture of the deep
      soft tissues of the mediastinum at the time of mediastinal debridement to
      determine the offending organism, if osteomyelitis is suggested by computed
      tomographic scan.

PMID- 17230093
TI  - Fascial release of the pectoralis major: a technique used in pectoralis major
      muscle closure of the mediastinum in cases of mediastinitis.
AB  - BACKGROUND: The authors' goal was to demonstrate a technique of gaining added
      width from the right pectoralis major muscle flap through muscle fascia release,
      with the hope of attaining sturdier, tension-free dead space closure of the
      debrided mediastinum in cases of mediastinitis. METHODS: The authors measured the
      preincisional and postincisional widths of the right pectoralis major flap
      following release of the fascia in nine patients who underwent mediastinal
      reconstruction using pectoralis major muscle flaps from 2002 to 2004 at the
      Detroit Medical Center. RESULTS: The average width of the nine muscles was 16.3
      +/- 1.7 cm before fascia release and 22.1 +/- 1.3 cm after release. The average
      increase in width was 5.8 +/- 1.3 cm, with a 95 percent confidence interval of
      4.8 to 6.8 cm. A value of p < 0.0001 indicated that this increase in width was
      statistically significant. After fascial release, the width of the muscles
      increased by an average of 26.1 percent, with a 95 percent confidence interval of
      21.6 to 30.6 percent. CONCLUSIONS: The authors present a new technique that can
      be used to gain additional width from the right pectoralis major muscle in cases
      of mediastinal reconstruction using the pectoralis major muscle flap. With the
      added 26 percent of width obtained from the right pectoralis major muscle with
      fascia release, the authors contend that a sturdier and tension-free closure of
      the mediastinal dead space can be obtained, further expanding the indications for
      use of the pectoralis major muscle flap as the sole closure modality in even the
      most complicated cases of mediastinitis.

PMID- 17230094
TI  - Management of severe open ankle injuries.
AB  - BACKGROUND: Functional outcome after reconstruction of open ankle injuries has
      not been well presented in the literature. The authors present the functional
      results of 24 patients who sustained complex ankle injuries. METHODS: Patients
      were assessed using three scoring systems (a modified A/O score, the Enneking
      score, and the AOFAS) and subdivided into two groups: those primarily treated at
      Charing Cross Hospital according to strict protocols combining orthopedic and
      plastic surgical techniques (group P) and those secondarily treated who were
      transferred to Charing Cross Hospital after initial management at a remote unit
      (group S). RESULTS: There were nine patients (37.5 percent) in group P and 15
      (62.5 percent) in group S. Eighteen patients (75 percent) underwent free-tissue
      transfer. Sixteen patients (67 percent) were assessed (group P, n = 7; group S, n
      = 9) for return of function using the Enneking score. Mean time to assessment was
      10.5 months for group P and 11.4 months for group S. Mean Enneking percentage
      score was 75 for group P and 72.2 for group S. There were no significant
      differences (p > 0.05) between these scores. The mean time to union was 19 weeks
      (n = 5) for group P and 24 weeks (n = 7) for group S. The mean AOFAS Ankle
      Hindfoot Scores were comparable to the Enneking scores when independent observers
      undertook this assessment. Most patients in both groups reported difficulty with
      descent of stairs. CONCLUSIONS: Although the authors were able to achieve a
      similar return of function for both groups, group S patients needed at least one
      more operation. In cases of ankle fracture where there is significant soft-tissue
      injury (either closed or open), representing a complex injury, the authors
      recommend making no attempt to internally fix the fracture and instead referring
      the patient to a specialist center for combined orthoplastic attention. If this
      is not immediately at hand, screw fixation of the medial malleolus should be
      undertaken after open reduction. The lateral malleolus should not be internally
      fixed, but should it require control, external fixation is the preferred method
      of skeletal stabilization.

PMID- 17230095
TI  - Perforator-plus flaps: a new concept in traditional flap design.
AB  - BACKGROUND: Conventional fasciocutaneous flaps in reconstructive surgery,
      especially in the lower extremities, have limited utility. Traditional flaps are
      essentially random pattern, often require delays, and are limited in mobility and
      reach. Islanded fasciocutaneous flaps pedicled on perforators can be raised
      anywhere on the body and have a reliable blood supply and greater freedom of
      movement. However, venous compromise is a common problem. METHODS: A new approach
      to raising conventional fasciocutaneous flaps while including and retaining
      perforators in their substance was used to offset these disadvantages. This
      concept offers a dual blood supply to the flap from the dissected perforator plus
      the flap base. The approach was attempted in 12 cases and used successfully in
      10. In two cases, the flaps were converted to pure islanded perforator flaps
      because of limited movement. Fasciocutaneous perforator-plus flaps were used in
      six patients with lower limb trauma and one patient with postburn elbow
      contracture. Peninsular flaps were planned to include known or identified
      perforators, which were dissected to allow mobility. RESULTS: All flaps survived
      completely and none exhibited venous compromise. In three patients, perforator
      plus flaps were used to the medial hemisoleus muscle while providing coverage to
      exposed tibial fractures. The muscle flap was based either proximally or
      distally, and a segmental perforator was dissected and retained. There were no
      complications relating to flap congestion or necrosis except wound infection in
      two patients, one each in the fasciocutaneous and muscle flap groups. Both
      responded to conservative treatment. No case required reoperation. CONCLUSION:
      The perforator-plus flap appears to be a versatile and reliable option in lower
      limb injuries and other diverse indications, in both the emergency and the
      elective settings.

PMID- 17230096
TI  - Reconstruction of a large gluteal soft-tissue defect with the double-opposing V-Y
      fasciocutaneous advancement flap.

PMID- 17230097
TI  - Microvascular reconstruction in burn and electrical burn injuries of the severely
      traumatized upper extremity.
AB  - BACKGROUND: As the versatility and variability of free flaps have significantly
      increased during recent years, so have the indications for free tissue
      transplantation in burn reconstruction expanded. METHODS: The authors report
      retrospectively the results of 42 free flaps for upper extremity reconstruction
      in 35 severely burned patients using 13 different free flaps. This experience
      enabled the authors to establish reconstructive principles pertinent to the type
      of injury (burn versus high-voltage injuries) and the timing of reconstruction
      procedures. RESULTS: In high-voltage injuries (n = 17), early free flap coverage
      with muscular flaps was the most frequently used type of reconstruction. The
      reconstruction site was predominately the forearm. In burn injuries, free flap
      coverage was performed during a later stage of the treatment course.
      Reconstruction with cutaneous or fascial flaps was the preferred method. The
      elbow and dorsum of the hand underwent defect coverage in most circumstances. For
      reconstruction of complex or large defects (n = 6), combined "chimeric" flaps
      were used. Overall, the flap failure rate was 12 percent (n = 5). Interestingly,
      there was a relationship between flap failure rate and timing of the procedure.
      Four of five flap failures occurred within 5 to 21 days after trauma, and all
      five flap failures occurred between 5 days and 6 weeks. No flap failure occurred
      during secondary reconstruction. CONCLUSIONS: The authors' data demonstrate that
      burn and high-voltage injuries are distinct entities, each requiring custom
      tailored reconstructive solutions for limb salvage. Even if the authors' flap
      failures all occurred during the first 6 weeks, it should not be forgotten that
      this type of coverage is the only alternative to amputation in selected cases.

PMID- 17230098
TI  - Endoscopically assisted sural nerve harvest for upper extremity posttraumatic
      nerve defects: an evaluation of functional outcomes.
AB  - BACKGROUND: Peripheral nerve injuries in the upper extremity often require
      interposition of sural nerve grafts for reconstruction. Due to the poor donor
      site appearance with standard techniques, and the potential for trauma to the
      nerve because of poor visualization during the harvest when the stepladder
      technique is used, the endoscope has been employed for nerve harvest. METHODS:
      From January of 1997 until December of 2003, 15 patients with an average age of
      27.5 years with posttraumatic upper limb nerve defects of the ulnar, median, or
      posterior interosseous nerves (crush, cutting, or avulsion injuries) underwent
      reconstruction with endoscopically harvested sural nerve. The nerves were
      harvested using atraumatic techniques under video monitor visualization. The
      functional results of sensation and motor function were assessed using British
      Medical Research Council scales. RESULTS: All patients regained at least
      cutaneous pain and tactile sensibility, with most regaining two-point
      discrimination (nine patients achieved S3+). Two patients achieved complete
      recovery (S4). The 11 patients with motor nerve involvement achieved between M1+
      and M5 after the initial reconstruction. Eight patients required a total of one
      immediate and nine secondary procedures to achieve the final outcome. The
      procedures included tenolysis (three patients), intrinsic tendon transfers (four
      patients), and opponensplasty (three patients). At the 4-year mean follow-up,
      grip power was M5 in 13 patients (86.7 percent) and M4 in two patients (13.3
      percent). CONCLUSIONS: Upper extremity sensory and motor nerve defects can be
      reconstructed with interposition of endoscopically harvested sural nerve grafts.
      The procedure is reliable, quick, and atraumatic, and results in reasonable motor
      and sensory recovery.

PMID- 17230099
TI  - Financial impact of hand surgery programs on academic medical centers.
AB  - BACKGROUND: This study analyzes the financial performance of hand surgery in the
      Department of Surgery at the University of Michigan. This analysis can serve as a
      reference for other medical centers in the financial evaluation of a hand surgery
      program. METHODS: Fiscal year 2004 billing records for all patients (n = 671) who
      underwent hand surgery procedures were examined. The financial data were
      separated into professional revenues and costs (relating to the hand surgery
      program in the Section of Plastic Surgery) and into facility revenues and costs
      (relating to the overall University of Michigan Health System). Professional net
      revenue was calculated by applying historical collection rates to procedural and
      clinic charges. Facility revenue was calculated by applying historical collection
      rates to the following charge categories: inpatient/operating room, clinic
      facility, neurology/electromyography, radiology facilities, and occupational
      therapy. Total professional costs were calculated by adding direct costs and
      allocated overhead costs. Facility costs were obtained from the hospital's cost
      accounting system. Professional and facility incomes were calculated by
      subtracting costs from revenues. RESULTS: The net professional revenue and total
      costs were 1,069,836 and 1,027,421 dollars, respectively. Professional operating
      income was 42,415 dollars, or 3.96 percent of net professional revenue. Net
      facility revenue and total costs were 5,500,606 and 4,592,534 dollars,
      respectively. Facility operating income was 908,071 dollars, or 16.51 percent of
      net facility revenues. CONCLUSIONS: While contributing to the academic mission of
      the institution, hand surgery is financially rewarding for the Department of
      Surgery. In addition, hand surgery activity contributes substantially to the
      financial well-being of the academic medical center.

PMID- 17230100
TI  - Anatomical study of factors contributing to zygomatic complex fracture
      instability in human cadavers.
AB  - BACKGROUND: Stable reduction of fractures of the zygomatic complex is essential
      to avoid long-term aesthetic, sensory, and ocular consequences. Delayed collapse
      or relapse after reduction of fractures of the zygomatic complex is attributed to
      muscle forces, when there has been no additional trauma. A number of studies have
      identified the masseter muscle as a contributor, but none has described the role
      of the temporalis muscle. METHODS: The origins of the temporalis muscle were
      examined in six cadaveric dissections. The temporal and zygomatic regions were
      exposed through a temporoparietal flap. Bone cuts were made above and below the
      frontozygomatic suture in the lateral orbital margin. The lateral orbital margin
      was then fractured and reflected laterally on its periosteum so that muscle
      attachments could be seen clearly. RESULTS: In all six dissections, the authors
      found that the temporalis muscle took origin not only from the floor of the
      temporal fossa and temporalis fascia but also from the lateral margin of the
      orbit and the frontal process of the zygomatic bone as far down as the body of
      the zygoma. CONCLUSIONS: The authors postulate that the functional forces exerted
      by this muscle on the zygomatic complex cause postoperative distraction at the
      frontozygomatic suture. The authors' findings provide further anatomical evidence
      to support internal fixation of all fractures of the zygomatic complex, even
      those that are considered clinically stable, if permanent flattening of the
      cheekbone is to be avoided.

PMID- 17230102
TI  - Progressive changes of columella length and nasal growth after nasoalveolar
      molding in bilateral cleft patients: a 3-year follow-up study.
AB  - BACKGROUND: The purpose of this study was to assess the progressive changes of
      columella length and nasal growth after presurgical nasoalveolar molding and
      primary cheiloplasty in bilateral complete cleft lip-cleft palate infants.
      METHODS: Twenty-two consecutive complete bilateral cleft lip-cleft palate infants
      were included. All of them underwent nasoalveolar molding for columella
      lengthening and retraction of the premaxilla for 3 to 4.5 months before primary
      cheiloplasty. Standard 1:1 basilar photographs were taken before and after
      nasoalveolar molding, 1 week after cheiloplasty, and yearly for 3 years. Nasal
      height and width were measured directly on the photographs. RESULTS: The results
      revealed that columella length was significantly lengthened after nasoalveolar
      molding and was further improved after primary cheiloplasty. The columella
      decreased in length slightly in the first and second years postoperatively and
      started to increase in length slightly in the third year postoperatively, whereas
      the rest of the nose grew significantly in height year by year. This consequently
      appeared as relapse of columella length. The shortage of the columella length was
      1.9 mm. CONCLUSIONS: Both presurgical nasoalveolar molding and primary
      cheiloplasty lengthened the columella in bilateral cleft lip-cleft palate
      patients. However, there was a relative relapse in columella length because of
      the differential growth between the columella and the rest of the nose in the
      first and second years postoperatively.

PMID- 17230103
TI  - Microvascular reconstruction of the pediatric mandible.
AB  - BACKGROUND: Free tissue transfer for adult mandibular reconstruction is a well
      established technique; however, there are few reports of pediatric microvascular
      lower jaw reconstruction. METHODS: This retrospective study was undertaken to
      review the range of indications, choices, safety, and efficacy of pediatric free
      tissue transfer to the lower jaw. All patients underwent a parascapular,
      scapular, or fibula free tissue transfer. Flap choice was based on preoperative
      clinical examination, radiographic findings, need for linear or multiplanar
      mandibular reconstruction, need for dental restoration, severity of soft-tissue
      deficit, and peroneal artery anatomy. RESULTS: Over a 10-year period (1989 to
      1999), we performed eight free tissue transfers to reconstruct the mandibles of
      seven children, aged 6 to 17 years. Indications included radiation-induced
      hypoplasia (n = 1), postsurgical resection of fibrous dysplasia (n = 1),
      hemifacial microsomia (n = 3), Robin sequence with severe micrognathia (n = 1),
      and osteomyelitis (n = 1). The authors transferred four parascapular
      osseocutaneous, two scapular osseocutaneous, one fibular osseocutaneous, and one
      fibular osseous flap to reconstruct five ramus, four condyle, and two subtotal
      mandibular defects. All bony defects were successfully bridged and all osseous
      flaps successfully integrated. Postoperatively, mandibular symmetry and Angle
      class I occlusion were restored in all patients throughout the 10.5-year follow
      up period (range, 9 to 14 years). Two patients received osseointegrated dental
      implants. Our only complication was the partial loss of a skin paddle.
      CONCLUSION: Microvascular reconstruction of the pediatric mandible, in selected
      patients, is a safe, reliable procedure that provides the bone stock and soft
      tissue necessary to restore normal maxillomandibular growth and dental
      rehabilitation.

PMID- 17230104
TI  - Sagittal split ramus osteotomy with mandible reduction.
AB  - BACKGROUND: The sagittal split ramus osteotomy is a well-established procedure,
      and many authors have attempted various modifications of the surgical technique.
      Nowadays, it is widely acknowledged that people in Korea, Japan, and China prefer
      an oval face, the lower part of which is slender. Therefore, among facial
      contouring procedures, the mandible reduction procedure is the most popular
      procedure in these countries. It is quite difficult for patients to undergo two
      different procedures on almost the same region separately. METHODS: For patients
      who underwent sagittal split ramus osteotomy on their mandible for various
      reasons, the authors performed mandible reduction at the same time if necessary.
      In the event that two procedures are performed simultaneously, the risk would be
      higher regarding postoperative stability, but there was no significant problem in
      achieving stable occlusion after surgery through a rigid fixation technique and 2
      weeks of rigid intermaxillary fixation. RESULTS: The authors attained
      satisfactory aesthetic results and good postoperative stability by performing
      sagittal split ramus osteotomy and mandible reduction at the same time.
      CONCLUSION: This procedure is thought to be useful for patients who are to
      undergo sagittal split ramus osteotomy for various reasons and want to have a
      slender lower face.

PMID- 17230105
TI  - Evaluation of the sensory deficit after sural nerve harvesting in pediatric
      patients.
AB  - BACKGROUND: The sural nerve is a sensory nerve that innervates the proximal part
      of the lateral aspect of the foot. The sural nerve is often harvested for nerve
      grafting. Sensory loss in the area supplied by the sural nerve could be expected,
      causing a lack of protective sensation and a potential risk of injury. The
      sensory outcome of sural nerve harvesting has not been documented in children.
      The aim of this study was to evaluate the sensory deficit following sural nerve
      harvest in infants. METHODS: The authors conducted a controlled study. Evaluation
      and mapping of the sensory thresholds in the sural nerve distribution were
      performed using the Semmes-Weinstein monofilament method on four predetermined
      sites on the foot. A questionnaire was used to elicit subjective findings. The
      inclusion criteria were children older than 6 years who had undergone bilateral
      sural nerve harvesting for brachial plexus reconstruction in the first year of
      life. Normal volunteers served as controls. RESULTS: Fourteen patients and 14
      controls were enrolled in the study. Eighty-six percent of the feet that were
      operated on had a sensory deficit (p = 0.0001). The patients reported no concerns
      regarding the sensation of their feet. CONCLUSIONS: Sural nerve harvesting in
      children leaves a measurable sensory deficit; however, this deficit does not seem
      to have clinical implications for the patients.

PMID- 17230106
TI  - Aging of the midface bony elements: a three-dimensional computed tomographic
      study.
AB  - BACKGROUND: The face loses volume as the soft-tissue structures age. In this
      study, the authors demonstrate how specific bony aspects of the face change with
      age in both men and women and what impact this may have on the techniques used in
      facial cosmetic surgery. METHODS: Facial bone computed tomographic scans were
      obtained from 60 Caucasian patients (30 women and 30 men). The authors' study
      population consisted of 10 male and 10 female subjects in each of three age
      categories. Each computed tomographic scan underwent three-dimensional
      reconstruction with volume rendering, and the following measurements were
      obtained: glabellar angle (maximal prominence of glabella to nasofrontal suture),
      pyriform angle (nasal bone to lateral inferior pyriform aperture), and maxillary
      angle (superior to inferior maxilla at the articulation of the inferior maxillary
      wing and alveolar arch). The pyriform aperture area was also obtained. The t test
      was used to identify any trends between age groups. RESULTS: The glabellar and
      maxillary angle in both the male and female subjects showed a significant
      decrease with increasing age. The pyriform angle did not show a significant
      change between age groups for either sex. There was a significant increase in
      pyriform aperture area from the young to the middle age group for both sexes.
      CONCLUSIONS: These results suggest that the bony elements of the midface change
      dramatically with age and, coupled with soft-tissue changes, lead to the
      appearance of the aged face.

PMID- 17230108
TI  - Augmentation mentoplasty with diced high-density porous polyethylene.
AB  - BACKGROUND: Augmentation mentoplasty is a common procedure, applied especially in
      conjunction with rhinoplasty. Although various materials have been used for this
      procedure, diced high-density porous polyethylene (Medpor) has not been used so
      far. The purpose of this study was to evaluate the use of diced high-density
      porous polyethylene in chin augmentation. METHODS: A subperiosteal pocket is
      prepared through submental incision. A high-density porous polyethylene block is
      diced into 1 x 1.5-mm pieces, to be placed into the subperiosteal pocket as much
      as needed by wrapping into oxidized cellulose (Surgicel). Immediately after the
      incision is closed, shaping with external massage is performed and an external
      bandage is applied. RESULTS: This procedure was performed in 20 patients, in
      addition to rhinoplasty, with a mean follow-up of 14 months (range, 8 to 20
      months). Five to 14 mm of augmentation was achieved. There were no complications,
      except for early seroma formation in three patients, which required aspiration by
      syringe. It is easy to give shape to diced high-density porous polyethylene by
      means of massage 3 weeks after surgery. CONCLUSIONS: Diced high-density porous
      polyethylene in augmentation mentoplasty is cheap, easy to insert, and moldable
      by external massage, and has flexibility in conforming to the shape of the
      mandible. It also avoids all the disadvantages of monobloc implants, allowing
      postoperative ingrowth of fibrous tissues, precluding late displacement, and
      giving a natural feel to the reconstructed area.

PMID- 17230109
TI  - An alternative approach to brow lift fixation: temporoparietalis fascia, galeal,
      and periosteal imbrication.
AB  - BACKGROUND: Brow elevation is one of the goals of surgical rejuvenation
      procedures. In this article, the authors evaluate the results of a frontotemporal
      suspension-fixation technique by means of temporoparietalis
      fascia/galeal/periosteal flap imbrication through an open or endoscopically
      assisted approach. METHODS: A total of 32 female patients aged between 44 and 72
      years were operated on under local anesthesia and sedation. In 23 cases, the
      frontotemporal lift was associated with a cervicofacial lift through separate
      incisions and in 19 with an upper/lower blepharoplasty performed at the same time
      or subsequently. The open approach was used in 26 cases and a combined approach
      with endoscopic assistance and reduced temporal incisions was used in six cases.
      Preoperative and postoperative measurements were taken between the lower hairline
      of the eyebrow and the medial and lateral canthal angles. RESULTS: Lateral brow
      elevation ranged from 3 to 7 mm, with an average of 5 mm. A lasting result was
      observed during the follow-up period, with partial relapse in five cases.
      Complications consisted of two transient frontal paresthesias, remarkable
      periorbital bruising in four cases, and a transient decrease in temporal hair
      density in six cases (6 to 8 months). No permanent alopecia was observed.
      CONCLUSIONS: Brow elevation is an essential feature for a pleasing aesthetic
      result in the periorbital region. The best results are those achieved in
      association with blepharoplasty. This technique produces stable results, and the
      incidence of sequelae and complications is acceptable.

PMID- 17230110
TI  - Medial epicanthoplasty using the skin redraping method.
AB  - BACKGROUND: The presence of epicanthal folds and the absence of supratarsal folds
      are unique features in the eyelids of Asians. The resulting appearance leads many
      to seek cosmetic improvement in the medial canthal area. Although many techniques
      have been described for the elimination of epicanthal folds, scarring and design
      complexity are barriers that must still be overcome by surgeons. METHODS: From
      December of 2002 to December of 2004, the authors performed medial
      epicanthoplasties using the skin redraping method (tension-free epicanthoplasty)
      to correct epicanthal folds in the eyelids of 215 Asian patients. The authors'
      method is very simple to design and easy to perform. The procedure requires only
      the elevation of skin, eliminating volume of muscle, and trimming of skin. Other
      ancillary procedures, such as flap design, anchoring, plication, or subdermal
      fixation, are not required. RESULTS: Most of the patients obtained satisfactory
      results. No patients complained about visible scarring and none required revision
      surgery. Scarring can be avoided on the noticeable medial canthal region because
      the only incisions needed are supratarsal and subciliary incisions. The ability
      to avoid tension resulting from skin redraping is another important factor
      contributing to the minimization of scarring. CONCLUSIONS: The skin redraping
      method is simple to design and easy to perform. It does not create tension or
      visible scars on the medial canthal region.

PMID- 17230111
TI  - Effects of two different units of botulinum toxin type a evaluated by computed
      tomography and electromyographic measurements of human masseter muscle.
AB  - BACKGROUND: Masseteric hypertrophy is recognized as an asymptomatic enlargement
      of one or both masseter muscles. Botulinum toxin type A injection into the
      masseter muscle can be alternatively used as a noninvasive treatment for
      masseteric hypertrophy. The aim of this study was to evaluate the effects of two
      different quantities of botulinum toxin type A on the thickness and cross
      sectional area and electromyographic changes in the masseter muscle using
      computed tomography and electromyographic measurement. METHODS: Thirty-two Korean
      subjects were enrolled in this study. Twenty-five units of botulinum toxin type A
      was injected bilaterally in the masseter muscle of 16 subjects, and 35 U was
      injected bilaterally in the remaining 16. The thickness and cross-sectional area
      of the masseter muscle were measured at three positions before and 12 weeks after
      injection using computed tomography. The electromyographic changes in the
      masseter muscle during maximum voluntary clenching were also evaluated before and
      2, 4, 12, and 24 weeks after injection. The difference in the results was
      statistically analyzed. RESULTS: Statistically significant differences before and
      after injection were observed when the dimensions and electromyographic values of
      the masseter muscle were evaluated. However, there was no significant difference
      between the 25-U and 35-U injections of botulinum toxin type A. The least
      reduction of muscle thickness was found at the site farthest from the injection
      point. Several mild side effects were reported, all of which were temporary and
      localized. CONCLUSIONS: Botulinum toxin type A is effective in treating
      hypertrophy of the masseter muscle, but the dose of the toxin is not associated
      with its effectiveness within the limits of this study.

PMID- 17230112
TI  - Liposuction breast reduction: a prospective trial in African American women.
AB  - BACKGROUND: Recently published case reports and outcome studies support the use
      of liposuction alone as an effective technique for ameliorating symptoms of
      breast hypertrophy. This study is the first prospective trial to examine the
      effectiveness of liposuction breast reduction as a primary modality of breast
      reduction. In addition, this study examines the role that liposuction breast
      reduction can play in the treatment of African American women, given the known
      scarring difficulties that darker skinned patients can encounter with traditional
      breast reduction surgery. METHODS: Twenty African American women were recruited
      through newspaper and Internet advertisements. Patients aged 20 to 60 years were
      serially accepted to the study. Patients with a chief complaint of breast ptosis
      were excluded. No other exclusion criteria were used. Previously validated
      questionnaire instruments were used preoperatively and postoperatively to measure
      breast-related symptoms, general patient health perception, bodily pain, and self
      esteem. Comorbid conditions, demographics, financial status, prior treatments,
      and smoking history were also documented. RESULTS: Seventeen patients completed
      the preoperative and postoperative questionnaires. An average of 1075 cc of
      tissue was removed per breast during liposuction breast reduction surgery.
      Postoperative assessment showed a significant decrease in breast-related
      symptoms, a significant decrease in patient pain, and a significant improvement
      in overall patient health perception. CONCLUSIONS: Liposuction breast reduction
      is a useful breast reduction modality in the properly selected patient. African
      American women, who may traditionally forego breast reduction surgery because of
      scarring, are excellent candidates for this type of reduction procedure.

PMID- 17230117
TI  - The golden age of seniors: for how long?

PMID- 17230114
TI  - Dynamics of hospital-based plastic surgery.
AB  - BACKGROUND: Legislative regulations, decreasing reimbursements for office
      procedures, and malpractice premiums have transformed plastic surgery from an
      office-based specialty into a hospital-based one. Simultaneously, hospital
      economics has altered, wherein the "business model" has all but subsumed the old
      "medical care" model. Integration between plastic surgeons and the new hospital
      structure has been difficult for both. Limited understanding of the financial
      dynamics of hospital-based practices, unfamiliarity with the administrative
      processes, and resistance to accept and assimilate changes by both sides pose
      hurdles, in some situations even forcing plastic surgeons out of hospital
      settings. METHODS: Using well-defined financial terminology, changing national
      development in health care policy, and hospital-based administrative strategies
      as a backdrop, this study finds common ground for the plastic surgery specialty
      to coapt with the hospital. RESULTS: Key missing elements in the interaction
      between plastic surgeons and hospital administrations and ways of integrating
      these components are identified. To do so effectively, plastic surgeons must
      first understand the basic tenets of management that drive hospital
      administrators, participate at every level they can in guiding these processes,
      and assume leadership roles that will ultimately dictate the way they work and
      conduct their professional lives. CONCLUSIONS: It is critical that plastic
      surgeons engage in important processes that govern the economics of hospital
      based health care delivery. This commitment will also ensure that all three
      groups (the patients, physicians, and hospital administrators) achieve a degree
      of satisfaction. The message to plastic surgeons is clear: be proactive and lead
      a campaign of change.

PMID- 17230118
TI  - The "retro" look: is less more?

PMID- 17230120
TI  - Correction of involutional entropion with suborbicularis septal and lateral
      canthal tightening.

PMID- 17230121
TI  - On the ethics of composite tissue allotransplantation (facial transplantation).

PMID- 17230123
TI  - Dog bites in San Francisco.

PMID- 17230124
TI  - A novel reconstructive technique following central lumpectomy.

PMID- 17230125
TI  - Laboratory assessment of burn depth.

PMID- 17230128
TI  - Effective surgical treatment of cubital tunnel syndrome based on provocative
      clinical testing without electrodiagnostics.

PMID- 17230130
TI  - The role of the journal impact factor: choosing the optimal source of peer
      reviewed plastic surgery information.

PMID- 17230131
TI  - Form-pressure garments for pinna keloids as a better pressure therapy.

PMID- 17230132
TI  - Macrostoma repair: 15-year experience.

PMID- 17230133
TI  - Use of bilateral segmental ostectomy to correct malocclusion in the reconstructed
      mandible with a free fibular bone flap.

PMID- 17230134
TI  - Chest wall reconstruction using a prolene/hydroxyapatite paste sandwich.

PMID- 17230135
TI  - Multiple nonsyndromic spontaneous keloids in allergic disease.

PMID- 17230136
TI  - A new device for syringe-assisted liposuction.

PMID- 17230137
TI  - Modified abdominoplasty as a functional reconstruction for recurrent hydradenitis
      suppurativa of the lower abdomen and groin.

PMID- 17230138
TI  - Sawtooth flaps to release penoscrotal tethering in proximal hypospadias.

PMID- 17230139
TI  - Postoperative hydrophallus after penile lengthening: an experimental and clinical
      study.

PMID- 17230140
TI  - Fire in the operating room after reading a CME.

PMID- 17230142
TI  - Hospital stays, hospital charges, and in-hospital deaths among infants with
      selected birth defects--United States, 2003.
AB  - Birth defects (BDs) are conditions that 1) result from a malformation,
      deformation, or disruption in one or more parts of the body; 2) are present at
      birth; and 3) have a serious, adverse effect on health, development, or
      functional ability. BDs are leading causes of pediatric hospitalizations, medical
      expenditures, and infant mortality. To estimate national hospital charges and
      rates of in-hospital deaths for a greater number of specific BDs than estimated
      in previous reports, investigators at the University of Arkansas for Medical
      Sciences and CDC used the Healthcare Cost and Utilization Project 2003 Kids'
      Inpatient Database (KID), developed and distributed by the Agency for Healthcare
      Research and Quality. KID is a 10% sample of hospital discharges after
      uncomplicated births and an 80% sample of all other pediatric discharges from 36
      participating states. Data are weighted to represent all pediatric
      hospitalizations in the United States. The investigators analyzed hospital stays
      during 2003 for newborn infants with any of 35 BDs. This report describes the
      results of that analysis, which indicated substantial variation among BDs
      regarding average length of stay, average hospital charge, and the incidence of
      in-hospital deaths. Average length of stay was greatest for infants with
      surgically repaired gastroschisis or omphalocele. Average hospital charges were
      highest for infants with hypoplastic left heart syndrome and common truncus
      arteriosus. Although anencephaly, trisomy 13, and trisomy 18 were associated with
      the highest rates of in-hospital death, the largest total numbers of deaths
      associated with neonatal hospitalizations occurred in infants with diaphragmatic
      hernia and renal agenesis. Further studies are needed to distinguish outcomes for
      infants with isolated and multiple defects and to assess longer-term outcomes.

PMID- 17230143
TI  - Laboratory-confirmed non-O157 Shiga toxin-producing Escherichia coli-
      Connecticut, 2000-2005.
AB  - Shiga toxin-producing Escherichia coli (STEC) infection causes diarrhea that is
      often bloody and can result in potentially life-threatening hemolytic uremic
      syndrome (HUS). Escherichia coli O157:H7 is the most common cause of STEC
      infection in the United States, producing 73,000 illnesses annually, according to
      the last estimate in 1999. Unlike O157, however, little is known about the
      incidence of non-O157 strains. Because STEC other than O157 are not commonly
      identified, the incidence, trends, and epidemiology of non-O157 STEC are not well
      understood. To assess trends in Shiga toxin enzyme immunoassay (Stx EIA) testing
      by local clinical laboratories, the Connecticut Department of Public Health
      (CTDPH) analyzed results of confirmatory testing conducted in the state
      laboratory during 2000--2005. The findings indicated that a total of 403 STEC
      infections were reported by clinical laboratories in Connecticut, including 207
      identified as STEC by Stx EIA testing alone, and that the use of Stx EIA
      increased from 2000 to 2005. Use of Stx EIA without prompt culture confirmation
      can delay or prevent serotyping and subtyping of isolates and detection of both
      O157 and non-O157 STEC outbreaks. Public health authorities in all states should
      ensure that clinical laboratories forward Stx EIA-positive specimens to the state
      laboratory for isolation and identification of STEC, as recommended by the
      Association of Public Health Laboratories and CDC.

PMID- 17230144
TI  - Indicators for occupational health surveillance.
AB  - Each year, millions of the estimated 140 million U.S. workers are injured on the
      job or become ill from exposure to hazards at work. These work-related injuries
      and illnesses result in substantial human and economic costs for workers,
      employers, and society; estimated direct and indirect costs of work-related
      injuries and illnesses are approximately $170 billion annually. In 1998, the
      Council of State and Territorial Epidemiologists (CSTE) and CDC's National
      Institute for Occupational Safety and Health (NIOSH) convened a work group that
      identified priority occupational health conditions to be placed under
      surveillance, addressed cross-cutting surveillance concerns, and made
      recommendations regarding the role of states in a comprehensive nationwide
      surveillance system for work-related disease, injuries, and hazards. CSTE
      recommendations led to the generation of 19 occupational health indicators (OHIs)
      and one Employment Demographic Profile, which were developed during 2001-2003.
      The OHIs complement other guidelines for state-based occupational health
      surveillance to address overall state and national goals to improve public
      health. These OHIs are intended to help states build occupational health capacity
      by providing them with tools to collect and generate important, basic information
      concerning the occupational health status of the state population and to identify
      areas in which to focus prevention efforts. In 2005, CSTE released a report
      compiling OHI data from 13 states. NIOSH provides funding for the OHIs because
      they are now a required component of state-based cooperative agreements for
      occupational health surveillance. This report introduces the OHIs and describes
      CSTE's approach to developing this new occupational health surveillance tool.

PMID- 17230145
TI  - Astrophysics: quark matter in compact stars?
AB  - In a theoretical interpretation of observational data from the neutron star EXO
      0748-676, Ozel concludes that quark matter probably does not exist in the centre
      of neutron stars. However, this conclusion is based on a limited set of possible
      equations of state for quark matter. Here we compare Ozel's observational limits
      with predictions based on a more comprehensive set of proposed quark-matter
      equations of state from the literature, and conclude that the presence of quark
      matter in EXO 0748-676 is not ruled out.

PMID- 17230150
TI  - The database revolution.

PMID- 17230151
TI  - Leading by example.

PMID- 17230152
TI  - Capitol calling.

PMID- 17230154
TI  - Palaeontology journal will 'fuel black market'.

PMID- 17230155
TI  - Europe moves to secure its future energy supply.

PMID- 17230157
TI  - Concern as revived 1918 flu virus kills monkeys.

PMID- 17230158
TI  - Behind the hunt for the Higgs boson.

PMID- 17230159
TI  - Misconduct? It's all academic...

PMID- 17230160
TI  - Breeding cheats.

PMID- 17230161
TI  - Where are they now?

PMID- 17230163
TI  - Climate of opportunity.

PMID- 17230164
TI  - Turning back the clock.

PMID- 17230165
TI  - Biological robotics: working out the bugs.

PMID- 17230166
TI  - Statistics: conviction by numbers.

PMID- 17230167
TI  - Need to speak English puts burden on Asian scientists.

PMID- 17230168
TI  - Moon and Venus as worthy of exploration as Mars.

PMID- 17230169
TI  - Time to give due weight to the 'carbon footprint' issue.

PMID- 17230170
TI  - How a database of nuclear databases could help the effort to combat trafficking.

PMID- 17230171
TI  - Merging and emerging cohorts: not worth the wait.

PMID- 17230178
TI  - Galaxy morphology: out of order.

PMID- 17230172
TI  - Merging and emerging cohorts: necessary but not sufficient.

PMID- 17230179
TI  - Influenza: fatal immunity and the 1918 virus.

PMID- 17230180
TI  - Semiconductor electronics: trapped fast at the gate.

PMID- 17230182
TI  - Climate change: lessons from a distant monsoon.

PMID- 17230183
TI  - Polymer chemistry: sacrificial synthesis.

PMID- 17230184
TI  - Cell biology: a switch for S phase.

PMID- 17230185
TI  - High-temperature metal-organic magnets.
AB  - For over two decades there have been intense efforts aimed at the development of
      alternatives to conventional magnets, particularly materials comprised in part or
      wholly of molecular components. Such alternatives offer the prospect of realizing
      magnets fabricated through controlled, low-temperature, solution-based chemistry,
      as opposed to high-temperature metallurgical routes, and also the possibility of
      tuning magnetic properties through synthesis. However, examples of magnetically
      ordered molecular materials at or near room temperature are extremely rare, and
      the properties of these materials are often capricious and difficult to
      reproduce. Here we present a versatile solution-based route to a new class of
      metal-organic materials exhibiting magnetic order well above room temperature.
      Reactions of the metal (M) precursor complex bis(1,5-cyclooctadiene)nickel with
      three different organics A-TCNE (tetracyanoethylene), TCNQ (7,7,8,8
      tetracyanoquinodimethane) or DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone)-
      proceed via electron transfer from nickel to A and lead to materials containing
      Ni(II) ions and reduced forms of A in a 2:1 Ni:A ratio--that is, opposite to that
      of conventional (low Curie temperature) MA(2)-type magnets. These materials also
      contain oxygen-based species within their architectures. Magnetic
      characterization of the three compounds reveals spontaneous field-dependent
      magnetization and hysteresis at room temperature, with ordering temperatures well
      above ambient. The unusual stoichiometry and striking magnetic properties
      highlight these three compounds as members of a class of stable magnets that are
      at the interface between conventional inorganic magnets and genuine molecule
      based magnets.

PMID- 17230186
TI  - Reversible stress softening of actin networks.
AB  - The mechanical properties of cells play an essential role in numerous
      physiological processes. Organized networks of semiflexible actin filaments
      determine cell stiffness and transmit force during mechanotransduction,
      cytokinesis, cell motility and other cellular shape changes. Although numerous
      actin-binding proteins have been identified that organize networks, the
      mechanical properties of actin networks with physiological architectures and
      concentrations have been difficult to measure quantitatively. Studies of
      mechanical properties in vitro have found that crosslinked networks of actin
      filaments formed in solution exhibit stress stiffening arising from the entropic
      elasticity of individual filaments or crosslinkers resisting extension. Here we
      report reversible stress-softening behaviour in actin networks reconstituted in
      vitro that suggests a critical role for filaments resisting compression. Using a
      modified atomic force microscope to probe dendritic actin networks (like those
      formed in the lamellipodia of motile cells), we observe stress stiffening
      followed by a regime of reversible stress softening at higher loads. This
      softening behaviour can be explained by elastic buckling of individual filaments
      under compression that avoids catastrophic fracture of the network. The
      observation of both stress stiffening and softening suggests a complex interplay
      between entropic and enthalpic elasticity in determining the mechanical
      properties of actin networks.

PMID- 17230187
TI  - Seasonal characteristics of the Indian Ocean Dipole during the Holocene epoch.
AB  - The Indian Ocean Dipole (IOD)--an oscillatory mode of coupled ocean-atmosphere
      variability--causes climatic extremes and socio-economic hardship throughout the
      tropical Indian Ocean region. There is much debate about how the IOD interacts
      with the El Nino/Southern Oscillation (ENSO) and the Asian monsoon, and recent
      changes in the historic ENSO-monsoon relationship raise the possibility that the
      properties of the IOD may also be evolving. Improving our understanding of IOD
      events and their climatic impacts thus requires the development of records
      defining IOD activity in different climatic settings, including prehistoric times
      when ENSO and the Asian monsoon behaved differently from the present day. Here we
      use coral geochemical records from the equatorial eastern Indian Ocean to
      reconstruct surface-ocean cooling and drought during individual IOD events over
      the past approximately 6,500 years. We find that IOD events during the middle
      Holocene were characterized by a longer duration of strong surface ocean cooling,
      together with droughts that peaked later than those expected by El Nino forcing
      alone. Climate model simulations suggest that this enhanced cooling and drying
      was the result of strong cross-equatorial winds driven by the strengthened Asian
      monsoon of the middle Holocene. These IOD-monsoon connections imply that the
      socioeconomic impacts of projected future changes in Asian monsoon strength may
      extend throughout Australasia.

PMID- 17230188
TI  - Complex gas hydrate from the Cascadia margin.
AB  - Natural gas hydrates are a potential source of energy and may play a role in
      climate change and geological hazards. Most natural gas hydrate appears to be in
      the form of 'structure I', with methane as the trapped guest molecule, although
      'structure II' hydrate has also been identified, with guest molecules such as
      isobutane and propane, as well as lighter hydrocarbons. A third hydrate
      structure, 'structure H', which is capable of trapping larger guest molecules,
      has been produced in the laboratory, but it has not been confirmed that it occurs
      in the natural environment. Here we characterize the structure, gas content and
      composition, and distribution of guest molecules in a complex natural hydrate
      sample recovered from Barkley canyon, on the northern Cascadia margin. We show
      that the sample contains structure H hydrate, and thus provides direct evidence
      for the natural occurrence of this hydrate structure. The structure H hydrate is
      intimately associated with structure II hydrate, and the two structures contain
      more than 13 different hydrocarbon guest molecules. We also demonstrate that the
      stability field of the complex gas hydrate lies between those of structure II and
      structure H hydrates, indicating that this form of hydrate is more stable than
      structure I and may thus potentially be found in a wider pressure-temperature
      regime than can methane hydrate deposits.

PMID- 17230189
TI  - Aberrant innate immune response in lethal infection of macaques with the 1918
      influenza virus.
AB  - The 1918 influenza pandemic was unusually severe, resulting in about 50 million
      deaths worldwide. The 1918 virus is also highly pathogenic in mice, and studies
      have identified a multigenic origin of this virulent phenotype in mice. However,
      these initial characterizations of the 1918 virus did not address the question of
      its pathogenic potential in primates. Here we demonstrate that the 1918 virus
      caused a highly pathogenic respiratory infection in a cynomolgus macaque model
      that culminated in acute respiratory distress and a fatal outcome. Furthermore,
      infected animals mounted an immune response, characterized by dysregulation of
      the antiviral response, that was insufficient for protection, indicating that
      atypical host innate immune responses may contribute to lethality. The ability of
      influenza viruses to modulate host immune responses, such as that demonstrated
      for the avian H5N1 influenza viruses, may be a feature shared by the virulent
      influenza viruses.

PMID- 17230190
TI  - Promotion of Hras-induced squamous carcinomas by a polymorphic variant of the
      Patched gene in FVB mice.
AB  - Mice of the C57BL/6 strain are resistant to the development of skin squamous
      carcinomas (SCCs) induced by an activated Ras oncogene, whereas FVB/N mice are
      highly susceptible. The genetic basis of this difference in phenotype is unknown.
      Here we show that susceptibility to SCC is under the control of a carboxy
      terminal polymorphism in the mouse Ptch gene. F1 hybrids between C57BL/6 and
      FVB/N strains ((B6FVB)F1) are resistant to Ras-induced SCCs, but resistance can
      be overcome either by elimination of the C57BL/6 Ptch allele (Ptch(B6)) or by
      overexpression of the FVB/N Ptch allele (Ptch(FVB)) in the epidermis of K5Hras
      transgenic (B6FVB)F1 hybrid mice. The human Patched (PTCH) gene is a classical
      tumour suppressor gene for basal cell carcinomas and medulloblastomas, the loss
      of which causes increased signalling through the Sonic Hedgehog (SHH) pathway.
      SCCs that develop in PtchB6+/- mice do not lose the wild-type Ptch gene or show
      evidence of increased SHH signalling. Although Ptch(FVB) overexpression can
      promote SCC formation, continued expression is not required for tumour
      maintenance, suggesting a role at an early stage of tumour cell lineage
      commitment. The Ptch polymorphism affects Hras-induced apoptosis, and binding to
      Tid1, the mouse homologue of the Drosophila l(2)tid tumour suppressor gene. We
      propose that Ptch occupies a critical niche in determining basal or squamous cell
      lineage, and that both tumour types can arise from the same target cell depending
      on carcinogen exposure and host genetic background.

PMID- 17230191
TI  - Feedback inhibition of calcineurin and Ras by a dual inhibitory protein Carabin.
AB  - Feedback regulation of adaptive immunity is a fundamental mechanism for
      controlling the overall output of different signal transduction pathways,
      including that mediated by the T-cell antigen receptor (TCR). Calcineurin and Ras
      are known to have essential functions during T-cell activation. However, how the
      calcineurin signalling pathway is terminated in the process is still largely
      unknown. Although several endogenous inhibitors of calcineurin have been
      reported, none fulfils the criteria of a feedback inhibitor, as their expression
      is not responsive to TCR signalling. Here we identify an endogenous inhibitor of
      calcineurin, named Carabin, which also inhibits the Ras signalling pathway
      through its intrinsic Ras GTPase-activating protein (GAP) activity. Expression of
      Carabin is upregulated on TCR signalling in a manner that is sensitive to
      inhibitors of calcineurin, indicating that Carabin constitutes part of a negative
      regulatory loop for the intracellular TCR signalling pathway. Knockdown of
      Carabin by short interfering RNA led to a significant enhancement of interleukin
      2 production by antigen-specific T cells in vitro and in vivo. Thus, Carabin is a
      negative feedback inhibitor of the calcineurin signalling pathway that also
      mediates crosstalk between calcineurin and Ras.

PMID- 17230192
TI  - Coupling substrate and ion binding to extracellular gate of a sodium-dependent
      aspartate transporter.
AB  - Secondary transporters are integral membrane proteins that catalyse the movement
      of substrate molecules across the lipid bilayer by coupling substrate transport
      to one or more ion gradients, thereby providing a mechanism for the concentrative
      uptake of substrates. Here we describe crystallographic and thermodynamic studies
      of Glt(Ph), a sodium (Na+)-coupled aspartate transporter, defining sites for
      aspartate, two sodium ions and d,l-threo-beta-benzyloxyaspartate, an inhibitor.
      We further show that helical hairpin 2 is the extracellular gate that controls
      access of substrate and ions to the internal binding sites. At least two sodium
      ions bind in close proximity to the substrate and these sodium-binding sites,
      together with the sodium-binding sites in another sodium-coupled transporter,
      LeuT, define an unwound alpha-helix as the central element of the ion-binding
      motif, a motif well suited to the binding of sodium and to participation in
      conformational changes that accompany ion binding and unbinding during the
      transport cycle.

PMID- 17230193
TI  - Bias in association studies of systemic lupus erythematosus susceptibility due to
      geographical variation in the frequency of a programmed cell death 1 polymorphism
      across Europe.
AB  - We obtained eight collections of DNA samples from ethnically matched systemic
      lupus erythematosus (SLE) patients and controls from five European countries
      totaling 783 patients and 1210 controls. A highly significant cline in the
      frequency of the PD1.3 A allele was found among controls but not among SLE
      patients. The frequency of the PD1.3 A allele increased from the Northeast to the
      Southwest of Europe. The cline was clearly apparent (P=1.2 x 10(-6)) when data
      from controls of other five SLE susceptibility studies were included in the
      analysis. This variation has severely biased SLE association studies owing to the
      lack of parallel changes in SLE patients. As a consequence, the PD1.3 A allele
      was more common in SLE patients than in controls in the Northeast and Center of
      Europe, similar to controls in Southeast Europe, and less frequent than in the
      controls in the Southwest of the Continent. This dissociation in allele
      frequencies between SLE patients and controls in different subpopulations
      indicated that programmed cell death 1 variation and disease susceptibility are
      not independent but the type of relationship is currently unclear. As allele
      frequency clines are common in other polymorphisms their impact in genetic
      epidemiology studies should be carefully considered.

PMID- 17230194
TI  - Expression of human PTPN22 alleles.
AB  - Considering the female predominance in most of the autoimmune disorders that
      associate with the PTPN22 Trp620 variant and the complexity by which this variant
      influences immunologic tolerance, the objective of this study was to ascertain if
      the allele-specific expression of the disease-associated Arg620Trp polymorphism
      is affected by cis-acting or sex-specific trans-acting factor/s (e.g. sex
      hormones). The use of the allele-specific transcript quantification of the
      Arg620Trp encoding 1858T polymorphism revealed no difference in the expression of
      the 1858C- and T-alleles in non-stimulated peripheral blood mononuclear cells
      (PBMCs) from non-pregnant female subjects, male subjects or pregnant female
      subjects in first or third trimester (P=0.70), respectively. While the
      transcription of PTPN22 in anti-CD3/anti-CD28 stimulated PBMCs increased fourfold
      (P<0.0001) and 13-fold (P<0.0001) after 48 and 72 h of activation, respectively,
      the expression of PTPN22 1858C- and T-alleles increased to the same extent
      (P=0.64). The present result essentially excludes such phenomena as a partial
      explanation for the female predominance in most of the autoimmune disorders that
      associate with the PTPN22 Trp620 variant.

PMID- 17230195
TI  - Impact of the genetic restriction of virus-specific T-cell responses in hepatitis
      C virus infection.
AB  - The immunobiology of hepatitis C virus (HCV) is significantly influenced by the
      host immune response to the virus, especially by virus-specific T-cell responses.
      Virus-specific T cells are restricted by human leucocyte antigen class I and II
      molecules. Of note, associations between these polymorphic loci and outcome and
      course of HCV infection have been reported in large and well-documented cohorts.
      This review will briefly summarize these studies and focus especially on the
      immunological and virological basis for the reported associations. The outcome
      and course of HCV infection is most likely determined by a complex interplay of
      genetic, immunological and virological factors. A better understanding of these
      host-virus interactions is essential not only to gain better insights into the
      mechanisms of viral clearance and persistence but also for the development of new
      antiviral vaccine strategies.

PMID- 17230196
TI  - The evolution of gene regulation by transcription factors and microRNAs.
AB  - Changes in the patterns of gene expression are widely believed to underlie many
      of the phenotypic differences within and between species. Although much emphasis
      has been placed on changes in transcriptional regulation, gene expression is
      regulated at many levels, all of which must ultimately be studied together to
      obtain a complete picture of the evolution of gene expression. Here we compare
      the evolution of transcriptional regulation and post-transcriptional regulation
      that is mediated by microRNAs, a large class of small, non-coding RNAs in plants
      and animals, focusing on the evolution of the individual regulators and their
      binding sites. As an initial step towards integrating these mechanisms into a
      unified framework, we propose a simple model that describes the transcriptional
      regulation of new microRNA genes.

PMID- 17230197
TI  - Dynamic genome architecture in the nuclear space: regulation of gene expression
      in three dimensions.
AB  - The regulation of gene expression is mediated by interactions between chromatin
      and protein complexes. The importance of where and when these interactions take
      place in the nucleus is currently a subject of intense investigation. Increasing
      evidence indicates that gene activation or silencing is often associated with
      repositioning of the locus relative to nuclear compartments and other genomic
      loci. At the same time, however, structural constraints impose limits on
      chromatin mobility. Understanding how the dynamic nature of the positioning of
      genetic material in the nuclear space and the higher-order architecture of the
      nucleus are integrated is therefore essential to our overall understanding of
      gene regulation.

PMID- 17230198
TI  - Contributions of genomics to life-history theory.
AB  - Life-history theory seeks to understand the factors that produce variation in
      life histories that are found both among and within species. At the organismal
      level there is a well developed mathematical framework, and an important focus of
      the current research is determining the biological underpinnings of this
      framework, with particular attention to the causal mechanisms that underlie trade
      offs. Genomic approaches are proving useful in addressing this issue.

PMID- 17230199
TI  - Frizzled/PCP signalling: a conserved mechanism regulating cell polarity and
      directed motility.
AB  - Signalling through Frizzled (Fz)/planar cell polarity (PCP) is a conserved
      mechanism that polarizes cells along specific axes in a tissue. Genetic screens
      in Drosophila melanogaster pioneered the discovery of core PCP factors, which
      regulate the orientation of hairs on wings and facets in eyes. Recent genetic
      evidence shows that the Fz/PCP pathway is conserved in vertebrates and is crucial
      for disparate processes as gastrulation and sensory cell orientation. Fz/PCP
      signalling depends on complex interactions between core components, leading to
      their asymmetric distribution and ultimately polarized activity in a cell.
      Whereas several mechanistic aspects of PCP have been uncovered, the global
      coordination of this polarization remains debated.

PMID- 17230200
TI  - The evolution of sex: empirical insights into the roles of epistasis and drift.
AB  - Despite many years of theoretical and experimental work, the explanation for why
      sex is so common as a reproductive strategy continues to resist understanding.
      Recent empirical work has addressed key questions in this field, especially
      regarding rates of mutation accumulation in sexual and asexual organisms, and the
      roles of negative epistasis and drift as sources of adaptive constraint in
      asexually reproducing organisms. At the same time, new ideas about the evolution
      of sexual recombination are being tested, including intriguing suggestions of an
      important interplay between sex and genetic architecture, which indicate that sex
      and recombination could have affected their own evolution.

PMID- 17230201
TI  - Educating health-care professionals about genetics and genomics.
AB  - To biomedical researchers, this is the 'genome era'. Advances in genetics and
      genomics such as the sequence of the human genome, the human haplotype map, open
      access databases, cheaper genotyping and chemical genomics have already
      transformed basic and translational biomedical research. However, for most
      clinicians, the genome era has not yet arrived. For genomics to have an effect on
      clinical practice that is comparable to its impact on research will require
      advances in the genomic literacy of health-care providers. Here we describe the
      knowledge, skills and attitudes that genomic medicine will require, and
      approaches to integrate them into the health-care community.

PMID- 17230202
TI  - Advocacy groups as research organizations: the PXE International example.
AB  - Advocacy organizations for genetic diseases are increasingly becoming involved in
      biomedical research, particularly translational research, in order to meet the
      needs of the individuals that they serve. PXE International, an advocacy
      organization for the disease pseudoxanthoma elasticum, provides an example of how
      research can be accelerated by these groups. It has adopted methods that were
      pioneered by other advocacy organizations, and has integrated these along with
      new approaches into franchizable elements. The model has been followed for other
      conditions and has led to the establishment of a common infrastructure to enable
      advocacy groups to initiate, conduct and accelerate research.

PMID- 17230204
TI  - Gene therapy and stem cell therapy for cardiovascular diseases today: a model for
      translational research.
AB  - Clinical trials looking at ways to promote myocardial regeneration have reported
      that the administered therapies have either neutral effects or modest benefits of
      questionable impact. These somewhat disappointing results should emphasize the
      need for translational research, with bidirectional feedback between the basic
      research laboratory and the clinical arena. Such a translational pathway is
      illustrated by the quest to find an effective therapy for restenosis, which
      culminated in the development of sirolimus. At this point a move away from the
      bedside and a return to the bench seems necessary to better understand the
      mechanisms of action of progenitor cells and stimulating factors. Without such
      basic knowledge research might be prematurely discouraged and the opportunity to
      fully understand the true potential of cardiovascular regenerative therapy might
      be missed.

PMID- 17230205
TI  - Bone-marrow-derived cells for cardiac stem cell therapy: safe or still under
      scrutiny?
AB  - Cardiac stem cell therapy with bone-marrow-derived stem cells is a promising
      approach to facilitate myocardial regeneration after acute myocardial infarction
      or in congestive heart failure. The clinical data currently available seem to
      indicate that this approach is safe and is not associated with an increase in the
      number of adverse clinical events; nevertheless, the level of safety confidence
      is limited because of the small number of patients who have been treated and the
      absence of long-term clinical follow-up data. In order to establish the clinical
      safety of cardiac stem cell therapy, it will be necessary to collect additional
      data from both previous and ongoing clinical trials in subsets of patients
      relative to their background risk. Several conceptual safety concerns should also
      be addressed. These concerns relate to a number of operational mechanisms and
      include biological effects on differentiation, remote homing of transplanted stem
      cells, progression of atherosclerosis, and arrhythmias. The proactive scrutiny of
      these phenomena could eventually facilitate the translation of the promise of
      cardiac regeneration into a safe and effective therapy.

PMID- 17230206
TI  - Stem cell mobilization by granulocyte-colony-stimulating factor in acute
      myocardial infarction: lessons from the REVIVAL-2 trial.
AB  - Experimental studies and early-phase clinical trials suggest that mobilization of
      bone marrow stem cells by granulocyte-colony-stimulating factor (G-CSF) can be
      used to improve cardiac regeneration after acute myocardial infarction (AMI). In
      order to more fully evaluate this intervention in patients with AMI, we conducted
      the Regenerate Vital Myocardium by Vigorous Activation of Bone Marrow Stem Cells
      (REVIVAL-2) clinical trial. Following successful reperfusion by percutaneous
      coronary intervention for AMI, patients were randomly assigned to receive a
      subcutaneous daily dose of 10 microg/kg G-CSF or placebo for 5 days. Treatment
      with G-CSF produced a significant mobilization of stem cells. After 4-6 months
      the reduction in infarct size from baseline, as determined by technetium-99
      labeled single-photon-emission CT, did not differ significantly between the G-CSF
      group and the placebo group. Furthermore, the improvement in left ventricular
      ejection fraction, as assessed by late-enhancement MRI, did not differ
      significantly between the two groups. G-CSF treatment did not increase the risk
      of adverse clinical events and did not promote restenosis. Our trial demonstrates
      that stem cell mobilization by G-CSF does not improve infarct size, left
      ventricular function, or coronary restenosis in patients with AMI who have had
      successful mechanical reperfusion.

PMID- 17230207
TI  - Cell-enhancement strategies for the treatment of ischemic heart disease.
AB  - Cell therapy is a promising option for the treatment of ischemic diseases.
      Infusion or injection of stem or progenitor cells has improved neovascularization
      and heart function after ischemia in various experimental studies and clinical
      phase II and III trials. One potential limitation for cell therapy is a low rate
      of engraftment and persistence of cells in the ischemic tissue. Moreover,
      impairment of the number and function of patient-derived progenitor cells might
      limit the efficiency of autologous stem cell therapy. Therefore, strategies to
      augment cell function, survival, and homing could be crucial to improve success
      rates for cell therapy. Experimental studies have provided novel options for
      improving survival and function by transduction of stem or progenitor cells with
      prosurvival genes (e.g. Akt or telomerase). Pretreatment of cells with small
      molecules, such as statins, p38 inhibitors, or endothelial nitric oxide synthase
      enhancers, has been used to augment cell homing, integration, and functional
      recovery after induction of ischemia. Priming of the tissue by mechanical
      activation or application of growth factors might further improve recruitment and
      incorporation of cells. In this article we summarize the experimental studies
      providing novel concepts for cell-enhancement strategies to aid the treatment of
      peripheral artery occlusive and ischemic heart disease.

PMID- 17230208
TI  - Granulocyte-colony-stimulating factor in acute myocardial infarction: future
      perspectives after FIRSTLINE-AMI and REVIVAL-2.
AB  - Granulocyte-colony-stimulating factor (G-CSF) seems to have direct
      cardioprotective effects related to mobilization of autologous bone-marrow
      mononuclear CD34(+) cells. These properties have attracted the attention of
      researchers investigating new therapeutic strategies for acute myocardial
      infarction. The role of G-CSF in bone-marrow cell mobilization removes the need
      for bone-marrow aspiration and repeated invasive procedures. This factor, coupled
      with the fact that G-CSF can be administered by noninvasive subcutaneous
      injection, give this approach a potential advantage over other cell-therapy
      options. This article is intended to present a concise overview of the current
      experimental and clinical findings for G-CSF therapy after acute myocardial
      infarction. In particular, we discuss the conflicting findings from the front
      integrated revascularization and stem cell liberation in evolving acute
      myocardial infarction (FIRSTLINE-AMI) and the Regenerate Vital Myocardium by
      Vigorous Activation of Bone Marrow Stem Cells (REVIVAL-2) studies.

PMID- 17230209
TI  - Future investigations in stem cell activation with granulocyte-colony-stimulating
      factor after myocardial infarction.
AB  - Experimental data indicate that stem cell mobilization with granulocyte colony
      stimulating factor (G-CSF) might have potential as a novel therapeutic strategy
      for acute myocardial infarction. The prospective beneficial effects of G-CSF can
      be attributed mainly to a direct action on injured myocardium rather than on
      differentiation of mobilized bone marrow stem cells into cardiac myocytes. This
      article reviews the evidence for the potential cardioprotective effects of G-CSF
      and discusses future investigations regarding pharmacologic stem cell activation
      and mobilization with G-CSF in the setting of acute myocardial infarction.

PMID- 17230210
TI  - Launching a clinical program of stem cell therapy for cardiovascular repair.
AB  - Since the feasibility of stem cell therapy has been recognized, enthusiasm for
      this therapy has grown exponentially. Nevertheless, as professionals we must
      realize that this enthusiasm should relate not only to our scientific interest
      but also to the care of our patients. Within the next decade, patients' demand
      for the latest therapies is likely to rise because of changes in health care
      systems that will broaden availability. Stem cell therapy is likely to be among
      these in-demand treatments, and we must be prepared for this change. In this
      Review we discuss the basic principles of how to launch a clinical program for
      stem cell therapy for cardiovascular repair. First, we look at the composition of
      the program team. Second, we describe the different types of stem cells available
      in clinical practice. Third, we present in depth the two most widely applicable
      delivery approaches. Finally, we discuss selection of patients and approaches and
      clinical and imaging methods by which to evaluate the safety and efficacy of this
      therapy.

PMID- 17230211
TI  - Plasticity and cardiovascular applications of multipotent adult progenitor cells.
AB  - Cardiovascular disease is the leading cause of death worldwide, which has
      encouraged the search for new therapies that enable the treatment of patients in
      palliative and curative ways. In the past decade, the potential benefit of
      transplantation of cells that are able to substitute for the injured tissue has
      been studied with several cell populations, such as stem cells. Some of these
      cell populations, such as myoblasts and bone marrow cells, are already being used
      in clinical trials. The laboratory of CM Verfaillie has studied primitive
      progenitors, termed multipotent adult progenitor cells, which can be isolated
      from adult bone marrow. These cells can differentiate in vitro at the single-cell
      level into functional cells that belong to the three germ layers and contribute
      to most, if not all, somatic cell types after blastocyst injection. This
      remarkably broad differentiation potential makes this particular cell population
      a candidate for transplantation in tissues in need of regeneration. Here, we
      focus on the regenerative capacity of multipotent adult progenitor cells in
      several ischemic mouse models, such as acute and chronic myocardial infarction
      and limb ischemia.

PMID- 17230212
TI  - Mechanisms of action of mesenchymal stem cells in cardiac repair: potential
      influences on the cardiac stem cell niche.
AB  - Clinical and basic studies of cell-based myocardial therapy have proceeded at a
      rapid pace. Cell therapy could lead to successful cardiac regeneration or repair
      by any of three general mechanisms: differentiation of the administered cells
      into all of the cellular constituents of the heart; release of factors capable of
      paracrine signaling from the administered cells; and fusion of the administered
      cells with the existing constituents of the heart. Here, we argue that a fourth
      general mechanism could be operative: stimulation of endogenous repair by
      injected cells, which and might cause the regeneration of stem cell niches. In a
      porcine model of myocardial infarction, allogeneic mesenchymal stem cells
      stimulated substantial improvement in the ejection fraction, reduction of infarct
      size, and the growth of a rim of new cardiac tissue in the region in which the
      mesenchymal stem cells were injected. These effects occurred in the absence of
      definitive cardiac myocyte differentiation. After myocardial infarction, porcine
      hearts exhibit evidence of cardiac myocytes that have entered the cell cycle,
      neovascularization, and reduced levels of apoptosis. These data, in addition to
      new insights regarding the presence of endogenous cardiac stem cells, strongly
      support the concept that the heart could contain stem cell niches. Effective cell
      therapy could lead to restoration of these niches through multifaceted cell-cell
      interactions.

PMID- 17230213
TI  - The adult human heart as a source for stem cells: repair strategies with
      embryonic-like progenitor cells.
AB  - Adequate cell-based repair of adult myocardium remains an elusive goal because
      most cells that are used cannot generate mature myocardium sufficient to promote
      large functional improvements. Embryonic stem cells can generate both mature
      cardiocytes and vasculature, but their use is hampered by associated teratoma
      formation and the need for an allogeneic source. The detection of sca-1(+), c
      kit(+), or isl-1(+) cardiac precursors and the creation of cardiospheres from
      adult heart tissues suggest that a persistent population of immature progenitor
      cells is present in the mature myocardium. These cell populations probably
      represent stages along a continuum of cardiac stem cell development and
      differentiation. We report isolation from ventricle of uncommitted cardiac
      progenitor cells, which appear to resemble the more immature, common pool of
      embryonic lateral plate mesoderm progenitors that yield both myocardial and
      endocardial cells during normal cardiac development. Under controlled in vitro
      conditions and in vivo, these cells can differentiate into endothelial, smooth
      muscle, and cardiomyocyte lineages and can be isolated and expanded to clinically
      relevant numbers from adult rat myocardial tissue. In this article, we discuss
      the potential for autologous repair or even cardiac regeneration with cells that
      follow a developmental pathway similar to embryonic cardiac precursors but
      without the inherent limitations associated with undifferentiated embryonic stem
      cells.

PMID- 17230214
TI  - Chimerism and microchimerism of the human heart: evidence for cardiac
      regeneration.
AB  - For decades, it has been widely accepted that the heart is a terminally
      differentiated organ that is unable to regenerate. Studies of recipients of
      hearts donated by other humans have shed light on the regenerative potential of
      the human heart. Investigators have been able to trace the Y chromosome by
      fluorescence in situ hybridization or polymerase chain reaction, or both, in sex
      mismatched heart recipients. Cardiac chimerism has been reported, with
      concentrations of chimeric cells ranging from 0.04% to 10.0%. Cardiac chimerism
      after bone marrow or progenitor cell transplantation has also been reported to a
      low extent (approximately 0.20%), suggesting that a fraction of the extracardiac
      cells that colonize the myocardium are of bone marrow origin. Cardiac chimerism
      after pregnancy with male offspring (fetal cell microchimerism) has also been
      demonstrated. Cells of fetal origin have been shown to be capable of
      differentiating into myocardial cells. Collectively, we show that chimerism
      studies provide a proof of concept of a process that it is likely to be part of
      normal cardiac homeostasis in humans but apparently insufficient for cardiac
      repair in diseased hearts.

PMID- 17230215
TI  - Growth-factor-mediated cardiac stem cell activation in myocardial regeneration.
AB  - The concept of an intrinsic regenerative capacity of the adult mammalian
      myocardium owing to the presence of cardiac stem cells (CSCs) in the atria and
      ventricles is starting to be accepted by the cardiovascular research community.
      The identification of this cell population has improved the prospects for
      developing successful clinical protocols for human myocardial regeneration. In
      the normal adult myocardium, only a small fraction of CSCs undergo amplification
      and differentiation to replace the parenchymal cells lost by normal wear and
      tear. Physiological or pathological stimuli cause substantial activation of CSCs,
      which is mediated by a paracrine feedback loop between myocytes and CSCs. In
      response to stress, the myocytes produce growth factors and cytokines, for which
      CSCs have receptors, and autocrine, self-sustaining activation of growth-factor
      production is simultaneously triggered in the CSCs. These findings from human and
      animal studies led us to test whether in situ activation of CSCs by growth
      factors would be as effective as transplantation of CSCs into the regenerating
      myocardium after ischemia in an animal model that has relevance to humans. In a
      porcine model, we produced extensive and functionally relevant myocardial
      regeneration. Here, we discuss the properties of endogenous myocardial stem cells
      that might be exploited to produce clinical myocardial regeneration without the
      need for cell transplantation.

PMID- 17230216
TI  - Myocyte death and renewal: modern concepts of cardiac cellular homeostasis.
AB  - The adult mammalian myocardium has a robust intrinsic regenerative capacity
      because of the presence of cardiac stem cells (CSCs). Despite being mainly
      composed of terminally differentiated myocytes that cannot re-enter the cell
      cycle, the heart is not a postmitotic organ and maintains some capacity to form
      new parenchymal cells during the lifespan of the organism. Myocyte death and
      formation of new myocytes by the CSCs are the two processes that enable this
      organ to maintain a proper and uninterrupted cardiac output from birth to
      adulthood and into old age. CSCs are activated in response to pathological or
      physiological stimuli, whereby they enter the cell cycle and differentiate into
      new myocytes (and vessels) that significantly contribute to changes in myocardial
      mass. The future of regenerative cardiovascular medicine is arguably dependent on
      our success in dissecting the biology and mechanisms regulating the number,
      growth, differentiation, and aging of CSCs. This information will generate the
      means to manipulate CSC growth, survival, and differentiation and, therefore,
      will provide the tools for the design of more physiologically relevant clinical
      regeneration protocols. In this article, we review the developments in cardiac
      cell biology that might, in our opinion, have a broad impact on cardiovascular
      medicine.

PMID- 17230217
TI  - Mitochondrial oxidative metabolism is required for the cardiac differentiation of
      stem cells.
AB  - Cardiogenesis within embryos or associated with heart repair requires stem cell
      differentiation into energetically competent, contracting cardiomyocytes. While
      it is widely accepted that the coordination of genetic circuits with
      developmental bioenergetics is critical to phenotype specification, the metabolic
      mechanisms that drive cardiac transformation are largely unknown. Here, we aim to
      define the energetic requirements for and the metabolic microenvironment needed
      to support the cardiac differentiation of embryonic stem cells. We demonstrate
      that anaerobic glycolytic metabolism, while sufficient for embryonic stem cell
      homeostasis, must be transformed into the more efficient mitochondrial oxidative
      metabolism to secure cardiac specification and excitation-contraction coupling.
      This energetic switch was programmed by rearrangement of the metabolic
      transcriptome that encodes components of glycolysis, fatty acid oxidation, the
      Krebs cycle, and the electron transport chain. Modifying the copy number of
      regulators of mitochondrial fusion and fission resulted in mitochondrial
      maturation and network expansion, which in turn provided an energetic continuum
      to supply nascent sarcomeres. Disrupting respiratory chain function prevented
      mitochondrial organization and compromised the energetic infrastructure, causing
      deficient sarcomerogenesis and contractile malfunction. Thus, establishment of
      the mitochondrial system and engagement of oxidative metabolism are prerequisites
      for the differentiation of stem cells into a functional cardiac phenotype.
      Mitochondria-dependent energetic circuits are thus critical regulators of de novo
      cardiogenesis and targets for heart regeneration.

PMID- 17230218
TI  - Stem cells transform into a cardiac phenotype with remodeling of the nuclear
      transport machinery.
AB  - Nuclear transport of transcription factors is a critical step in stem cell
      commitment to a tissue-specific lineage. While it is recognized that nuclear
      pores are gatekeepers of nucleocytoplasmic exchange, it is unknown how the
      nuclear transport machinery becomes competent to support genetic reprogramming
      and cell differentiation. Here, we report the dynamics of nuclear transport
      factor expression and nuclear pore microanatomy during cardiac differentiation of
      embryonic stem cells. Cardiac progeny derived from pluripotent stem cells
      displayed a distinct proteomic profile characterized by the emergence of cardiac
      specific proteins. This profile correlated with the nuclear translocation of
      cardiac transcription factors. The nuclear transport genes, including
      nucleoporins, importins, exportins, transportins, and Ran-related factors, were
      globally downregulated at the genomic level, streamlining the differentiation
      program underlying stem cell-derived cardiogenesis. Establishment of the cardiac
      molecular phenotype was associated with an increased density of nuclear pores
      spanning the nuclear envelope. At nanoscale resolution, individual nuclear pores
      exhibited conformational changes resulting in the expansion of the pore diameter
      and an augmented probability of conduit occupancy. Thus, embryonic stem cells
      undergo adaptive remodeling of the nuclear transport infrastructure associated
      with nuclear translocation of cardiac transcription factors and execution of the
      cardiogenic program, underscoring the plasticity of the nucleocytoplasmic
      trafficking machinery in accommodating differentiation requirements.

PMID- 17230219
TI  - miles-apart-Mediated regulation of cell-fibronectin interaction and myocardial
      migration in zebrafish.
AB  - The migration of myocardial precursor cells towards the embryonic midline
      underlies the formation of the heart tube and is a key process of heart
      organogenesis. The zebrafish mutation miles-apart (mil), which affects the gene
      encoding a sphingosine-1-phosphate receptor, is characterized by defective
      migration of myocardial precursor cells and results in the formation of two
      laterally positioned hearts, a condition known as cardia bifida. The mechanism
      that disrupts myocardial migration in mil mutants remains largely unclear. To
      investigate how mil regulates this process, here we analyze the interactions
      between mil and other mediators of myocardial migration. We show that mil
      function is associated with the other known cardia bifida locus,
      natter/fibronectin (nat/fn), which encodes fibronectin, a major component of the
      extracellular matrix, in the control of myocardial migration. By using a primary
      culture system of embryonic zebrafish cells, we also show that signaling from the
      sphingosine-1-phosphate receptor regulates cell-fibronectin interactions in
      zebrafish. In addition, localized inhibition and activation of cell-fibronectin
      interactions during the stages of myocardial migration reveal that the temporal
      regulation of cell-fibronectin interaction by mil is required for proper
      myocardial migration. Our study reveals novel functional links between
      sphingosine-1-phosphate receptor signaling and cell-fibronectin interaction in
      the control of myocardial migration during zebrafish heart organogenesis.

PMID- 17230220
TI  - Cell-based gene therapy for the prevention and treatment of cardiac dysfunction.
AB  - A substantial need exists for new treatments to prevent and treat cardiac
      dysfunction. In the 1990s, there was great hope for gene therapy in this regard.
      Since that time, the focus has switched to cell therapy-in particular, therapy
      with the aim of inducing myocardial regeneration. Individually, gene and cell
      therapies still have substantial promise. Ultimately, however, the convergence of
      both techniques might be necessary to achieve improvements in cardiac function
      and more successful clinical outcomes in patients with cardiac dysfunction. This
      approach has already been adopted for treatment of malignancies. Several gene
      products are currently being studied, including growth factors and chemokines
      that can modulate the survival and function of cardiac myocytes following an
      ischemic event and influence remodeling of the left ventricle. However, several
      issues remain, including the optimization and characterization of cell types,
      selection of vectors for gene transfer, and identification of appropriate
      strategies for delivery. Here, we review the potential and need for cell-based
      gene therapy for the prevention and treatment of cardiac dysfunction and attempt
      to discuss the unresolved issues.

PMID- 17230221
TI  - Catheter-based stem cell and gene therapy for refractory myocardial ischemia.
AB  - Intramyocardial delivery of genes and cells derived from bone marrow has been
      evaluated in several small studies of 'no-option' symptomatic patients with
      chronic ischemic coronary artery disease. Clinical experience with
      intramyocardial gene delivery is limited to genes encoding isoforms of vascular
      endothelial cell growth factor. In the largest study (Euroinject One), 80
      patients were randomized to receive a plasmid encoding vascular endothelial cell
      growth factor 165 or placebo. The results of this study suggested no beneficial
      therapeutic effect of this strategy. The experience with stem cells is limited to
      use of autologous, nonexpanded, nonmanipulated bone-marrow-derived cells; thus,
      the number of injected stem cells reflects their natural proportion within the
      bone marrow. The results of these preliminary studies suggest this approach is
      feasible and has a high safety profile. Although no conclusion can yet be made
      regarding efficacy, the improved myocardial perfusion in all four studies
      described in this Review is encouraging. Data from assessments of individual
      patients, however, suggests a wide variability in response, underscoring the need
      for further bench and clinical investigations.

PMID- 17230222
TI  - Cardiac stem cells: isolation, expansion and experimental use for myocardial
      regeneration.
AB  - Cellular cardiomyoplasty (myogenic cell grafting) is actively being explored as a
      novel method to regenerate damaged myocardium. The adult human heart contains
      small populations of indigenous committed cardiac stem cells or multipotent
      cardiac progenitor cells, identified by their cell-surface expression of c-kit
      (the receptor for stem cell factor), P-glycoprotein (a member of the multidrug
      resistance protein family), and Sca-1 (stem cell antigen 1, a mouse hematopoietic
      stem cell marker) or a Sca-1-like protein. Cardiac stem cells represent a logical
      source to exploit in cardiac regeneration therapy because, unlike other adult
      stem cells, they are likely to be intrinsically programmed to generate cardiac
      tissue in vitro and to increase cardiac tissue viability in vitro. Cardiac stem
      cell therapy could, therefore, change the fundamental approach to the treatment
      of heart disease.

PMID- 17230223
TI  - Clinical trials in stem cell therapy: pitfalls and lessons for the future.
AB  - The first human trial of stem cell therapy for cardiovascular disease was
      performed 4 years ago. Since that time, almost a dozen studies have reported the
      early and late clinical effects of cell therapy in acute myocardial infarction
      and chronic ischemic cardiomyopathy. Initial nonrandomized trials universally
      showed slight improvement in the left ventricular ejection fraction. Later
      randomized, controlled trials, however, suggested a less significant effect. They
      showed either no difference between cell therapy and control treatment or a
      slight treatment benefit with cell therapy that is lost by 12 months' follow-up.
      These results have dampened the enthusiasm of some members of the scientific
      community for the continuation of clinical trials. Because early phase I trials
      should not be judged on issues other than safety, however, research is unlikely
      to be hindered. Indeed, the clinical studies reported so far have already taught
      us a lot about the biology of myocardial repair. Achieving clinical success will,
      however, probably require much more investment in basic and experimental
      research. Here, we address some of the current pitfalls in clinical cell therapy
      trials and lessons that should be learned as we face the challenges of the
      future.

PMID- 17230224
TI  - Myelofibrosis with a novel translocation, t(1;3)(q31;q23), and response to
      imatinib mesylate.

PMID- 17230225
TI  - Absence of JAK-2V617F point mutations in multiple myeloma.

PMID- 17230226
TI  - Lyn is an important component of the signal transduction pathway specific to
      FLT3/ITD and can be a therapeutic target in the treatment of AML with FLT3/ITD.
AB  - Fms-like tyrosine kinase 3 (FLT3) is expressed in hematopoietic progenitor cells.
      An internal tandem duplication (ITD) of FLT3 (FLT3/ITD) is the most frequent
      mutation in human adult acute myeloid leukemia (AML). FLT3/ITD contributes to the
      constitutive activation of FLT3 itself and its downstream signal components,
      mitogen-activated protein kinase and signal transducers and activators of
      transcription 5 (STAT5), and enables interleukin (IL)-3-dependent cell lines to
      grow autonomously. In the present study, we showed the specific association of
      FLT3/ITD with Lyn, which led to the phosphorylation of Lyn in vivo. We also
      demonstrated that FLT3/ITD receptors displayed a higher affinity to bind to Lyn
      than wild-type FLT3 receptors in vitro and that this affinity was relative to the
      intensity of tyrosil phosphorylation of the receptor. Both treatment with small
      interfering RNA (siRNA) targeting Lyn and the Src family kinase inhibitor PP2
      suppressed the IL-3-independent growth of FLT3/ITD-expressing 32D cells (FLT3/ITD
      32D), reducing the constitutive phosphorylation of Lyn and STAT5. PP2 treatment
      of mice transplanted with FLT3/ITD-32D cells blocked the onset of tumors and
      decreased the size of established tumors. These results demonstrate that Lyn is
      an important component of the signal transduction pathway specific to FLT3/ITD
      and can be a therapeutic target in the treatment of AML with FLT3/ITD.

PMID- 17230227
TI  - Mapping of MYC breakpoints in 8q24 rearrangements involving non-immunoglobulin
      partners in B-cell lymphomas.
AB  - Chromosomal translocations joining the immunoglobulin (IG) and MYC genes have
      been extensively reported in Burkitt's and non-Burkitt's lymphomas but data
      concerning MYC rearrangements with non-IG partners are scarce. In this study,
      8q24 breakpoints from 17 B-cell lymphomas involving non-IG loci were mapped by
      fluorescence in situ hybridization (FISH). In seven cases the breakpoint was
      inside a small region encompassing MYC: in one t(7;8)(p12;q24) and two
      t(3;8)(q27;q24), it was telomeric to MYC whereas in four cases, one
      t(2;8)(p15;q24) and three t(8;9)(q24;p13) it was located in a 85 kb region
      encompassing MYC. In these seven cases, partner regions identified by FISH
      contained genes known to be involved in lymphomagenesis, namely BCL6, BCL11A,
      PAX5 and IKAROS. Breakpoints were cloned in two t(8;9)(q24;p13), 2.5 and 7 kb
      downstream from MYC and several hundred kb 5' to PAX5 on chromosome 9, joining
      MYC to ZCCHC7 and to ZBTB5 exon 2, two genes encoding zinc-finger proteins. In
      these seven cases, MYC expression measured by quantitative reverse transcription
      polymerase chain reaction (RT-PCR) was significantly higher when compared to that
      of patients without 8q24 rearrangement (P=0.006). These results suggest that
      these rearrangements are the consequence of a non-random process targeting MYC
      together with non-IG genes involved in lymphocyte differentiation and lymphoma
      progression.

PMID- 17230228
TI  - Treatment of deletion 5q acute myeloid leukemia with lenalidomide.

PMID- 17230229
TI  - The pathogenesis of MALT lymphomas: where do we stand?
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is a heterogeneous form of a B
      cell non-Hodgkin's lymphoma with extranodal location. The gastrointestinal tract
      is the most common site of disease, but involvement of multiple other organ
      systems has been documented. Four translocations, t(11;18)(q21;q21),
      t(1;14)(p22;q32), t(14;18)(q32;q21) and t(3;14)(p13;q32), are specifically
      associated with MALT lymphoma. Remarkably, the genes targeted by at least three
      of these translocations are involved in one and the same pathway, leading to the
      activation of nuclear factor-kappaB (NF-kappaB). This review presents MALT
      lymphoma as a model of how sustained inflammation increases the risk of genotoxic
      insults and how these genetic events initiate oncogenesis.

PMID- 17230230
TI  - A practical guide to defining high-risk myeloma for clinical trials, patient
      counseling and choice of therapy.
AB  - Clinical outcomes for multiple myeloma (MM) are highly heterogeneous and it is
      now clear that pivotal genetic events are the primary harbingers of such
      variation. These findings have broad implications for counseling, choice of
      therapy and the design and interpretation of clinical investigation. Indeed, as
      in acute leukemias and non-hodgkins lymphoma, we believe it is no longer
      acceptable to consider MM a single disease entity. As such, the accurate
      diagnosis of MM subtypes and the adoption of common criteria for the
      identification and stratification of MM patients has become critical. Herein, we
      provide a consensus high-risk definition and offer practical guidelines for the
      adoption of routine diagnostic testing. Although acknowledging that more refined
      classifications will continue to be developed, we propose that the definition of
      high-risk disease (any of the t(4;14), t(14;16), t(14;20), deletion 17q13,
      aneuploidy or deletion chromosome 13 by metaphase cytogenetics, or plasma cell
      labeling index >3.0) be adopted. This classification will identify most of the
      25% of MM patients for whom current therapies are inadequate and for whom
      investigational regimens should be vigorously pursued. Conversely, the 75% of
      patients remaining have more favorable outcomes using existing - albeit non
      curative - therapeutic options.

PMID- 17230231
TI  - Epigenetic alterations complement mutation of JAK2 tyrosine kinase in patients
      with BCR/ABL-negative myeloproliferative disorders.
AB  - An acquired autoactivating mutation with a V617F amino-acid substitution in the
      JAK2 tyrosine kinase is frequently found in BCR/ABL-negative myeloproliferative
      disorders (MPD). Hypermethylation of CpG islands within gene promoter regions is
      associated with transcriptional inactivation and represents an important
      mechanism of gene silencing in the pathogenesis of hematopoietic malignancies. In
      this study, we determined the DNA methylation status of 13 cancer-related genes
      in the context of JAK2 mutations in 39 patients with MPD. Genes analyzed for
      hypermethylation were SOCS-1, SHP-1, E-cadherin, MGMT, TIMP-2, TIMP-3, p15, p16,
      p73, DAPK1, RASSF1A, RARbeta2 and hMLH1. We found at least one hypermethylated
      gene in 15/39 MPD patient specimens, and in 6/39 samples aberrant methylation of
      the negative cytokine regulator SOCS-1 was present. The JAK2V617F mutation was
      found in 21/39 patients as determined by allele-specific polymerase chain
      reaction. Hypermethylation of SOCS-1 was observed in 3/21 patients with an
      autoactivating JAK2 mutation and in 3/18 patients with wild-type JAK2. Our
      results suggest that epigenetic inactivation of SOCS-1 may be a complementary
      mechanism to the JAK2V617F mutation in the pathogenesis of MPD that leads to
      dysregulation of JAK-STAT signal transduction and thus contributes to growth
      factor hypersensitivity.

PMID- 17230232
TI  - Apolipoprotein E and low-density lipoprotein receptor gene polymorphisms in
      dyslipidemias-associated essential hypertension.

PMID- 17230233
TI  - Urinary albumin excretion is associated with impaired flow- and nitroglycerin
      mediated brachial artery dilatation in hypertensive adults.
AB  - We investigated whether the urinary albumin/creatinine ratio (UACR), a measure of
      albuminuria, is associated with non-invasive measures of arterial function in
      hypertensive adults without known coronary heart disease (CHD) or stroke. UACR
      was measured in the first voided morning urine sample in 469 non-Hispanic white
      hypertensive individuals (mean age 62.2+/-9.8 years, 41% men) belonging to
      hypertensive sibships. High-resolution ultrasonography of the brachial artery was
      used to assess flow-mediated dilatation (FMD)--an endothelium-dependent response-
      and nitroglycerin-mediated dilatation (NMD)--an endothelium-independent response.
      Because of skewed distribution, UACR was log transformed after addition of 0.1.
      The association of log (UACR+0.1) with FMD and NMD, before and after adjustment
      for CHD risk factors, serum creatinine, and hypertension medication and statin
      use was assessed using linear regression analyses. In univariable analyses,
      variables associated with lower FMD were greater age, male sex, history of
      smoking, lower high-density lipoprotein (HDL) cholesterol, higher serum
      creatinine and higher log (UACR+0.1); variables associated with lower NMD were
      greater age, male sex, higher systolic blood pressure, lower HDL cholesterol,
      higher serum creatinine and higher log (UACR+0.1). In separate stepwise
      multivariable regression analyses that adjusted for conventional CHD risk
      factors, serum creatinine and hypertension medication and statin use, higher log
      (UACR+0.1) was associated with lower brachial artery FMD (P=0.035) and NMD
      (P=0.0002). These findings highlight the association of increased urinary albumin
      excretion with impaired vascular reactivity in hypertensive individuals.

PMID- 17230234
TI  - Surrogate estimates of insulin sensitivity in subjects with hypertension.
AB  - The purpose of the study is to compare surrogate estimates of insulin sensitivity
      with a directly measured insulin sensitivity index, steady-state plasma glucose
      (SSPG) from insulin suppression test (IST), in subjects with hypertension. Two
      hundred and twenty-eight hypertensive patients who received IST for SSPG were
      included for analysis. Estimates from fasting measurements alone, homeostasis
      model assessment for insulin resistance (HOMA-IR) and quantitative insulin
      sensitivity check index (QUICKI)), and indices from fasting and/or 2 h samples
      (ISI(0,120) and ISI(TX)) were calculated. In addition to Pearson and partial
      correlations, variance-component models were used to test the relationship
      between surrogate estimates of insulin sensitivity and SSPG. A large proportion
      of variance owing to covariates in the variance-component models indicated the
      goodness of model fit, irrespective of the independence among variables. SSPG was
      positively correlated with logarithmic transformation (Log) (HOMA-IR) and
      negatively correlated with QUICKI, Log (ISI(0,120)) and ISI(TX) (all P<0.0001).
      Log (ISI(0,120)) seemed to have a better correlation with SSPG (r=-0.72) than
      other measures in partial correlation. The proportion of variance owing to all
      covariates of Log (ISI(0,120)) and ISI(TX) were larger than those of Log (HOMA
      IR) and QUICKI in the variance-component models. After adjustments for
      demographic and obesity covariates, the proportion of variance explained by Log
      (ISI(0,120)) were largest among the surrogate measures in the variance-component
      models. Our results showed that ISI(0,120) and ISI(TX) correlated better with
      SSPG than those used fasting measures alone (HOMA-IR and QUICKI). Log
      (ISI(0,120)) currently showing the strongest association with SSPG than other
      estimates is adaptable for use in large studies of hypertension.

PMID- 17230235
TI  - Dual-peak long-period fiber gratings with enhanced refractive index sensitivity
      by finely tailored mode dispersion that uses the light cladding etching
      technique.
AB  - We have experimentally investigated the mode dispersion property and refractive
      index sensitivity of dual-peak long-period fiber gratings (LPGs) that were
      sensitized by hydrofluoric acid (HF) etching. The nature of the coupled cladding
      modes close to the dispersion turning point makes the dual-peak LPGs
      ultrasensitive to cladding property, permitting a fine tailoring of the mode
      dispersion and index sensitivity by the light cladding etching method using HF
      acid of only 1% concentration. As an implementation of an optical biosensor, the
      etched device was used to detect the concentration of hemoglobin protein in a
      sugar solution, showing a sensitivity as high as 20 nm/1%.

PMID- 17230236
TI  - Source coherence impairments in a direct detection direct sequence optical code
      division multiple-access system.
AB  - We demonstrate that direct sequence optical code- division multiple-access (DS
      OCDMA) encoders and decoders using sampled fiber Bragg gratings (S-FBGs) behave
      as multipath interferometers. In that case, chip pulses of the prime sequence
      codes generated by spreading in time-coherent data pulses can result from
      multiple reflections in the interferometers that can superimpose within a chip
      time duration. We show that the autocorrelation function has to be considered as
      the sum of complex amplitudes of the combined chip as the laser source coherence
      time is much greater than the integration time of the photodetector. To reduce
      the sensitivity of the DS-OCDMA system to the coherence time of the laser source,
      we analyze the use of sparse and nonperiodic quadratic congruence and extended
      quadratic congruence codes.

PMID- 17230237
TI  - Ultrathin cameras using annular folded optics.
AB  - We present a reflective multiple-fold approach to visible imaging for high
      resolution, large aperture cameras of significantly reduced thickness. This
      approach allows for reduced bulk and weight compared with large high-quality
      camera systems and improved resolution and light collection compared with
      miniature conventional cameras. An analysis of the properties of multiple-fold
      imagers is presented along with the design, fabrication, and testing of an
      eightfold prototype camera. This demonstration camera has a 35 mm effective focal
      length, 0.7 NA, and 27 mm effective aperture folded into a 5 mm total thickness.

PMID- 17230238
TI  - Paraxial matrix description of astigmatic and cylindrical mirror resonators with
      twisted axes for laser spectroscopy.
AB  - A complete matrix description of ray-optic propagation in an astigmatic multipass
      cell is presented, with expressions for the coupling of coordinates. A pair of
      transforms puts the 4 x 4 paraxial system matrix into block-diagonal form,
      allowing a solution using Sylvester's theorem. A variation on the Jones matrix
      calculus is employed wherein the ray coordinates on both resonator mirrors are
      simultaneously represented as a single state of the system. The formulations are
      applicable to resonators with any degree of astigmatism and axial twist. Examples
      are presented of beam paths and the boundary shapes of beam spots. The shape of
      the pattern boundaries, as a function of the coordinate coupling coefficient,
      influences the practical availability of patterns.

PMID- 17230239
TI  - Thin-filament pyrometry with a digital still camera.
AB  - A novel thin-filament pyrometer is presented. It involves a consumer-grade color
      digital still camera with 6 megapixels and 12 bits per color plane. SiC fibers
      were used and scanning-electron microscopy found them to be uniform with
      diameters of 13.9 micro m. Measurements were performed in a methane-air coflowing
      laminar jet diffusion flame with a luminosity length of 72 mm. Calibration of the
      pyrometer was accomplished with B-type thermocouples. The pyrometry measurements
      yielded gas temperatures in the range of 1400-2200 K with an estimated
      uncertainty of +/-60 K, a relative temperature resolution of +/-0.215 K, a
      spatial resolution of 42 mum, and a temporal resolution of 0.66 ms. Fiber aging
      for 10 min had no effect on the results. Soot deposition was less problematic for
      the pyrometer than for the thermocouple.

PMID- 17230240
TI  - Photopatterning of polybutadiene substrates by interferometric ultraviolet
      lithography: fabrication of phospholipid microarrays.
AB  - Gratings are written holographically with low power (10 mW/cm(2)) 244 nm UV light
      on thin films of polybutadiene rubber polymer. The increase of hydrophilicity
      wettability of polybutadiene films is measured over UV-exposed regions.
      Sequential fabrication of two orthogonal gratings results in hydrophilic
      microarrays having applications as functionalized substrates for immobilizing
      biomolecules. This is demonstrated by immobilizing a phospholipid in a microarray
      pattern.

PMID- 17230241
TI  - Optical characterization of porous silicon and crystalline silicon by the Kramers
      Kronig method.
AB  - The electronic structure of porous silicon (PS) has been characterized by optical
      reflectance spectra analyses. Using a Cary-500 spectrometer, the reflectance
      spectra of PS are measured in the photon energy range of 0.4-6 eV. The spectral
      responses of optical constants are calculated for PS and Si by Kramers-Kronig
      analysis. The analysis clarified strong evidence for widening and direct bandgaps
      for PS samples. Also, the optical constants of PS layers as a function of
      porosity have been studied. Our results indicate that PS retains some of the
      characteristic optical features of crystalline Si. However, in the visible
      region, PS shows that the imaginary part of the complex refractive index
      increases, and the real part decreases as porosity increases. This feature could
      be related to the surface roughness of PS and its role in surface absorption and
      scattering.

PMID- 17230242
TI  - Closed equation for the normal incidence reflectance of thin films on absorbing
      substrates.
AB  - The optical constants of thin films can be obtained from inversion of
      spectrophotometric measurements by using minimization gradient methods. The
      computational approach of these minimization methods requires closed compact
      formulas for reflectance and/or transmittance. For normal incidence closed
      compact formulations for the direct transmittance, both for thin films on
      transparent or absorbing substrates, and for the reflectance of thin films on
      transparent substrates, are available in the literature. We report here a closed
      compact formula to evaluate reflectance spectra of thin films on absorbing
      substrates, and it is shown that for vanishing substrate absorption this new, to
      the best of our knowledge, approach gives the same results obtained from the
      formulation corresponding to thin films supported by transparent substrates.

PMID- 17230243
TI  - Wide-aperture no-moving-parts optical beam profiler using liquid-crystal
      displays.
AB  - To the best of our knowledge, we demonstrate the first no-moving-parts largest
      aperture profiler design that is also cost effective. Specifically exploited is
      the large-scale production of thin-film transistor liquid-crystal displays (LCDs)
      to produce a high intrinsic reliability low-cost profiler. Today, the maximum
      beam diameter under test can reach 70 cm using 117 cm diagonal LCDs. Experiments
      conducted with the laboratory LCD profiler include 1D and 2D knife-edge
      profiling, 2D pinhole profiling, and beam divergence measurements.

PMID- 17230244
TI  - Reflection and refraction of narrow Gaussian beams with general astigmatism at
      tilted optical surfaces: a derivation oriented toward lens design.
AB  - The formulas for the reflection and refraction of a narrow Gaussian beam with
      general astigmatism at a tilted optical surface are derived by ray-tracing
      techniques. The propagation direction of the reflected and refracted beams is
      computed by tracing the central ray of the incident beam, and the characteristic
      parameters of the respective wavefronts are worked out by applying the formulas
      developed for the generalized ray tracing. Moreover, the Gaussian form of the
      reflected and refracted amplitude distributions along the transverse coordinates
      is determined by requiring the matching of the incident, reflected, and refracted
      light spots on the optical surface. No limiting assumptions are made regarding
      the form of the optical interface or the orientation of the incident astigmatic
      wavefront. In the end, to illustrate a simple application of these formulas, the
      reflection of a Gaussian beam at a conicoid is considered, and a simple property
      of the conicoidal mirrors is reported.

PMID- 17230245
TI  - Illumination system using LED sources for pocket-size projectors.
AB  - An illumination system using LED sources for pocket-size projectors is designed.
      Its color gamut is much larger than the sRGB standard. The maximum theoretical
      efficiency of this system is 29.98% by non-imaging theory-based calculations. To
      analyze the system model, 1.5 x 10(6) rays are traced by using the LightTools
      software. The total light flux that illuminates the digital micromirror device is
      44 lm and the American National Standards Institute 13-point uniformity on the
      surface is 91.55%, -91.15% with a system efficiency of 28.3%. The calculations
      are in good agreement with the simulation results. The illumination system can be
      used for personal pocket-size projectors providing a 15-20 in. (38-51 cm) color
      display with the brightness comparable with a laptop.

PMID- 17230246
TI  - Particle sizing with a fast polar nephelometer.
AB  - We reported previously the design of a polar nephelometer that uses a rotational
      confocal imaging setup to enable fast scanning of the scattering phase function
      within a field of view of 55 degrees . The full dynamic range of the detection
      system can be used by increasing the signal-to-noise ratio by means of averaging
      successive scans. The calibration of the angular response of the instrument is
      achieved by obtaining the transfer function of the optical detection system using
      Rayleigh scatterers. Accurate particle sizing of individual polystyrene spheres
      (ranging from 1.5 to 9 micro m in diameter) in aqueous suspension is achieved by
      maximizing a correlation coefficient between precalculated tables of Mie phase
      functions and data obtained from the polar nephelometer. Good correlation is
      achieved between experimental and theoretical data, proving the functioning of
      the instrument as a fast and convenient particle sizer.

PMID- 17230247
TI  - Parasitic diffuse reflection in a Fourier transform spectrometer yielding
      subharmonic ghosts and line-shape distortion.
AB  - When using a high-resolution Fourier transform spectrometer (FTS) in a cube
      corner configuration, subharmonic ghosts are observed in the spectrum. These
      ghosts are attributable to parasitic diffuse reflections on the mirrors of the
      FTS arm. The reflected beams skip a part of the interferometer and travel a
      different path from the main beam thus experiencing a smaller optomechanical
      gain. These reflections are present in the reference laser channel as well as on
      the measurement channel, and each affect the estimated spectrum differently. The
      sampling grid generated by the reference laser has periodic errors that are
      synchronized with the fringe signal. The measured spectrum can therefore exhibit
      sampling jitter ghosts at submultiples of the reference laser wavenumber in
      addition to its own additive subharmonics. The diffuse reflection experiencing
      the nominal optomechanical gain, such as in a plane-mirror configuration, will
      impact directly on the instrument line shape and on the radiometric accuracy of
      the spectrometer since some radiation is not propagating at the expected angles
      in the instrument.

PMID- 17230248
TI  - Parallel computing of a digital hologram and particle searching for microdigital
      holographic particle-tracking velocimetry.
AB  - We have developed a parallel algorithm for microdigital-holographic particle
      tracking velocimetry. The algorithm is used in (1) numerical reconstruction of a
      particle image computer using a digital hologram, and (2) searching for
      particles. The numerical reconstruction from the digital hologram makes use of
      the Fresnel diffraction equation and the FFT (fast Fourier transform), whereas
      the particle search algorithm looks for local maximum graduation in a
      reconstruction field represented by a 3D matrix. To achieve high performance
      computing for both calculations (reconstruction and particle search), two memory
      partitions are allocated to the 3D matrix. In this matrix, the reconstruction
      part consists of horizontally placed 2D memory partitions on the x-y plane for
      the FFT, whereas, the particle search part consists of vertically placed 2D
      memory partitions set along the z axes. Consequently, the scalability can be
      obtained for the proportion of processor elements, where the benchmarks are
      carried out for parallel computation by a SGI Altix machine.

PMID- 17230249
TI  - Coherence estimation in synthetic aperture radar data based on speckle noise
      modeling.
AB  - In the past we proposed a multidimensional speckle noise model to which we now
      include systematic phase variation effects. This extension makes it possible to
      define what is believed to be a novel coherence model able to identify the
      different sources of bias when coherence is estimated on multidimensional
      synthetic radar aperture (SAR) data. On the one hand, low coherence biases are
      basically due to the complex additive speckle noise component of the Hermitian
      product of two SAR images. On the other hand, the availability of the coherence
      model permits us to quantify the bias due to topography when multilook filtering
      is considered, permitting us to establish the conditions upon which information
      may be estimated independently of topography. Based on the coherence model, two
      coherence estimation approaches, aiming to reduce the different biases, are
      proposed. Results with simulated and experimental polarimetric and
      interferometric SAR data illustrate and validate both, the coherence model and
      the coherence estimation algorithms.

PMID- 17230250
TI  - Theoretical wave structure function when the effect of the outer scale is
      significant.
AB  - The wave structure function (WSF) for a plane wave, calculated from the basic
      Rytov theory, is usually expressed as 6.88(r/r(0))(5/3), but this does not
      include the effect of a finite outer scale (or of a nonzero inner scale) of
      turbulence. When separation distance r is only 5% of the outer scale, this
      expression overpredicts the WSF by a factor of approximately 2. Accurate
      evaluations of the Rytov formulas are given for the WSFs of plane and spherical
      waves in Kolmogorov and von Karman turbulence and for the structure function of
      the atmosphere's index of refraction. Simple formulas make the results easy to
      use.

PMID- 17230251
TI  - Conical and biconical ultra-high-Q optical-fiber nanowire microcoil resonator.
AB  - New 3D geometries of the optical nanowire microcoil resonator are suggested and
      investigated theoretically. The dependence of the Q factor on coupling parameters
      is calculated and compared for three different profiles. Results suggest that
      ultra-high-Q resonators can be fabricated more easily when the nanowire microcoil
      resonator has a biconical profile.

PMID- 17230252
TI  - Adaptive optics implementation with a Fourier reconstructor.
AB  - Adaptive optics takes its servo feedback error cue from a wavefront sensor. The
      common Hartmann-Shack spot grid that represents the wavefront slopes is usually
      analyzed by finding the spot centroids. In a novel application, we used the
      Fourier decomposition of a spot pattern to find deviations from grid regularity.
      This decomposition was performed either in the Fourier domain or in the image
      domain, as a demodulation of the grid of spots. We analyzed the system, built a
      control loop for it, and tested it thoroughly. This allowed us to close the loop
      on wavefront errors caused by turbulence in the optical system.

PMID- 17230253
TI  - General analysis of slab lasers using geometrical optics.
AB  - A thorough and general geometrical optics analysis of a slab-shaped laser gain
      medium is presented. The length and thickness ratio is critical if one is to
      achieve the maximum utilization of absorbed pump power by the laser light in such
      a medium; e.g., the fill factor inside the slab is to be maximized. We point out
      that the conditions for a fill factor equal to 1, laser light entering and
      exiting parallel to the length of the slab, and Brewster angle incidence on the
      entrance and exit faces cannot all be satisfied at the same time. Deformed slabs
      are also studied. Deformation along the width direction of the largest surfaces
      is shown to significantly reduce the fill factor that is possible.

PMID- 17230254
TI  - Study of performance of a He-Ne laser having an annular gain zone.
AB  - A He-Ne laser with an annular gain zone is studied theoretically. It is
      demonstrated that the He-Ne medium in the annular discharge zone possesses enough
      gain to maintain laser oscillation. A multipass ring resonator, which is composed
      of two annular spherical mirrors, is described, and it is shown that the
      resonator is suitable for extracting optical energy from the He-Ne medium in the
      annular gain zone. Considering the availability of population inversion in the
      traveling-wave cavity and the influence of the crossover of the folded light beam
      in the resonator on the output power, a calculation formula for the output power
      of the laser with the multipass ring resonator is given. Calculating results
      prove that a 1 W output of the He-Ne laser can be obtained by a 1 m length
      annular discharge zone.

PMID- 17230255
TI  - Dispensed polymer waveguides and laser-fabricated couplers for optical
      interconnects on printed circuit boards.
AB  - Optical interconnects can provide chip-to-chip data communication with much
      needed bandwidth as processor speed and density keep growing. Optical waveguides
      and couplers are essential components for implementing optical interconnections.
      Techniques for directly dispensing polymer waveguides in laser-ablated trenches
      on printed circuit boards and for fabricating optical couplers are presented for
      quick prototype of optical interconnects. High-quality UV curable polymer
      waveguides were routinely fabricated. High-efficiency couplers, blazed grating
      couplers on sloped waveguides, sloped facet metal film couplers, and reflective
      undercut facet couplers can be fabricated by using excimer laser ablation.

PMID- 17230256
TI  - Effect of multiple transverse modes in self-mixing sensors based on vertical
      cavity surface-emitting lasers.
AB  - We investigate the effect of coexisting transverse modes on the operation of self
      mixing sensors based on vertical-cavity surface-emitting lasers (VCSELs). The
      effect of multiple transverse modes on the measurement of displacement and
      distance were examined by simulation and in laboratory experiment. The simulation
      model shows that the periodic change in the shape and magnitude of the self
      mixing signal with modulation current can be properly explained by the different
      frequency-modulation coefficients of the respective transverse modes in VCSELs.
      The simulation results are in excellent agreement with measurements performed on
      single-mode and multimode VCSELs and on self-mixing sensors based on these
      VCSELs.

PMID- 17230257
TI  - Detection of vapors of explosives and explosive-related compounds by ultraviolet
      cavity ringdown spectroscopy.
AB  - The detection of vapors of dinitrobenzenes and dinitrotoluenes by UV cavity
      ringdown spectroscopy (CRDS) was investigated. Absorption cross sections at 248
      nm were estimated by measurements on saturated vapors and compared with solution
      phase values. The computed subparts per 10(9) detection sensitivity with no
      effort at preconcentration was demonstrated through measurements on diluted
      flows. The factors affecting measurements on 1 atm total pressure were
      considered, and it was demonstrated that Rayleigh scattering by air will reduce
      the detection sensitivity by 5%-10%. The UV absorption spectra of these compounds
      are broad, resulting in a relatively poor selectivity for single-wavelength
      measurements with the UV CRDS technique.

PMID- 17230258
TI  - Biomechanics from research to industry.

PMID- 17230259
TI  - Injury tolerance and response of the ankle joint in dynamic dorsiflexion.
AB  - Forced dorsiflexion in frontal vehicle crashes is considered a common cause of
      injury to the ankle joint. Although a few studies have been published on the
      dynamic fracture tolerance of the ankle in dorsiflexion, this work reexamines the
      topic with increased statistical power, adds an evaluation of articular cartilage
      injury, and utilizes methods to detect the true time of fracture. The objective
      of this study was to measure the response and injury tolerance of the human ankle
      in a loading condition similar to that found in a vehicle crash with toepan
      intrusion. A test fixture was constructed to apply forefoot impacts to twenty
      cadaveric lower limbs, that were anatomically intact distal to the femur mid
      diaphysis. Specimen instrumentation included implanted tibial and fibular load
      cells, accelerometers, angular rate sensors, and an acoustic sensor. Following
      the tests, specimens were radiographed and dissected to determine the extent of
      injury. Eleven of the twenty specimens sustained fracture of the ankle joint.
      Fractures of the medial malleolus were the most common, while two specimens
      sustained bimalleolar fractures, and two a talar neck fracture. Other injuries
      included ligament tears, osteochondral fractures, and cartilage abrasions.
      Analysis of the acoustic emission indicated that fracture did not always occur at
      the peak ankle moment. Based on the results of this study, an ankle joint moment
      of 59 N-m represents a 25% risk of ankle fracture in dorsiflexion for a 50(th)
      percentile male. When applied to the Thor-Lx dummy, the 25% risk of injury occurs
      at 36 degrees of dorsiflexion as measured by the ankle potentiometer.

PMID- 17230260
TI  - Lateral and posterior dynamic bending of the mid-shaft femur: fracture risk
      curves for the adult population.
AB  - The purpose of this study was to develop injury risk functions for dynamic
      bending of the human femur in the lateral-to-medial and posterior-to-anterior
      loading directions. A total of 45 experiments were performed on human cadaver
      femurs using a dynamic three-point drop test setup. An impactor of 9.8 kg was
      dropped from 2.2 m for an impact velocity of 5 m/s. Five-axis load cells measured
      the impactor and support loads, while an in situ strain gage measured the failure
      strain and subsequent strain rate. All 45 tests resulted in mid-shaft femur
      fractures with comminuted wedge and oblique fractures as the most common fracture
      patterns. In the lateral-to-medial bending tests the reaction loads were 4180 +/-
      764 N, and the impactor loads were 4780 +/- 792 N. In the posterior-to-anterior
      bending tests the reaction loads were 3780 +/- 930 N, and the impactor loads were
      4310 +/- 1040 N. The difference between the sum of the reaction forces and the
      applied load is due to inertial effects. The reaction loads were used to estimate
      the mid-shaft bending moments at failure since there was insufficient data to
      include the inertial effects in the calculations. The resulting moments are
      conservative estimates (lower bounds) of the mid-shaft bending moments at failure
      and are appropriate for use in the assessment of knee restraints and pedestrian
      impacts with ATD measurements. Regression analysis was used to identify
      significant parameters, and parametric survival analysis was used to estimate
      risk functions. Femur cross-sectional area, area moment of inertia (I), maximum
      distance to the neutral axis (c), I/c, occupant gender, and occupant mass are
      shown to be significant predictors of fracture tolerance, while no significant
      difference is shown for loading direction, bone mineral density, leg aspect and
      age. Risk functions are presented for femur cross-sectional area and I/c as they
      offer the highest correlation to peak bending moment. The risk function that
      utilizes the most highly correlated (R2 = 0.82) and significant (p = 0.0001)
      variable, cross-sectional area, predicts a 50 percent risk of femur fracture of
      240 Nm, 395 Nm, and 562 Nm for equivalent cross-sectional area of the 5(th)
      percentile female, 50(th) percentile male, and 95(th) percentile male
      respectively.

PMID- 17230261
TI  - The Effect of Axial Load in the Tibia on the Response of the 90 degrees Flexed
      Knee to Blunt Impacts with a Deformable Interface.
AB  - Lower extremity injuries are a frequent outcome of automotive accidents. While
      the lower extremity injury criterion is based on fracture of bone, most injuries
      are of less severity. Recent studies suggest microscopic, occult fractures that
      have been shown to be precursors of gross bone fractures, may occur in the
      kneecap (patella) for impacts with rigid and deformable interfaces due to
      excessive levels of patello-femoral contact pressure. One method of reducing this
      contact pressure for a 90 degrees flexed knee is to provide a parallel pathway
      for knee impact loads into the tibial tuberosity. Yet, blunt loads onto the
      tibial tuberosity can cause posterior drawer motion of the tibia, leading to
      injury or rupture of the posterior cruciate ligament (PCL). Recently studies have
      shown that axial loads in the tibia, which are measured during blunt loading on
      the knee in typical automobile crashes, can induce anterior drawer motion of the
      tibia and possibly help unload the PCL. The purpose of the current study was to
      explore the effect of combined anterior knee loading (AKL) and axial tibia
      loading (ATL), on response and injury for the 90 degrees flexed human knee. In
      repeated impacts with increasing ATL the stiffness of the knee to an AKL impact
      increased. For a 3 kN AKL, the stiffness of the knee increased approximately 26%
      when the ATL was increased from 0 kN to 2 kN. For 6 kN and 9 kN AKL, the
      stiffness was increased approximately 17% and 20%, respectively, when the ATL was
      increased from 0 kN (uniaxial) to 4 kN (biaxial). The effect, however, was not
      statistically significant at the 9 kN AKL level. The posterior tibial drawer was
      shown to increase with increased AKL and decrease with increased levels of ATL at
      an average of 0.3 mm per kN ATL for both the 3 kN and 6 kN ATL scenarios. For 9
      kN AKL this drawer displacement was significantly reduced for biaxial versus
      uniaxial impacts, from 7.4+/-1.4 mm to 5.8+/-0.6 mm, respectively. Additionally,
      the percentage of the load carried by the tibial tuberosity increased with an
      ATL. For AKL impacts of 3, 6, and 9 kN, the percentage of load carried by the
      tibial tuberosity increased from 2.1% (range 0-19%) to 4.9% (0-36%), 2.1% (0-15%)
      to 6.9% (0-36%), and 8.7% (0-25%) to 12.7% (0-33%), respectively, between
      uniaxial and biaxial tests. The biaxial loading scenario also resulted in a
      reduction of the patello-femoral (PF) contact force as the ATL was increased. Ten
      knee impacts resulted in PCL tears at an average peak load of 12.7+/-2.4 kN in
      biaxial impacts (n=5) and 12.0+/-3.1 kN for uniaxial impacts (n=5). These PCL
      injured specimens had an average age of 62+/-11.3 years. The remaining specimens
      (n=11, 78+/-12.9 years of age) had bone fractures at approximately 8.9+/-3.1 kN.
      This study showed that combinations of compressive ATL and AKL reduced the PF
      contact force and had a stiffening effect on the response of the knee impacting a
      stiff but deformable interface. Furthermore, ATL reduced the posterior drawer of
      the tibia, which is the current basis for PCL injury in the knee, although it did
      not reduce the incidence of PCL injury in this study. While the current injury
      tolerance criterion reflects the vulnerability of the PCL to injury by limiting
      tibial drawer to 15 mm, the current dummy design does not incorporate the
      stiffening effect of an ATL that may occur at the same time as knee contact with
      an instrument panel during a typical automotive crash.

PMID- 17230262
TI  - Below Knee Impact Responses using Cadaveric Specimens.
AB  - Knee injuries represent about 10% of all injuries suffered during car crashes.
      Efforts to assess the injury risk to the posterior cruciate ligament (PCL) have
      been based on a study available in the literature (Viano et al., 1978), in which
      only two of the five knees tested had PCL ruptures. The aims of the current study
      were to repeat the study with a higher number of samples, study the effects of
      other soft tissues on knee response, and assess the adequacy of the experimental
      setup for the identification of a PCL tolerance. A total of 14 knees were tested
      using a high-speed materials testing machine. Eight were intact knees (with the
      patella and all the muscular and ligamentous structures), three were PCL-only
      knees (patella and all the muscular and ligamentous structures other than the PCL
      removed), and the last three were PCL-only knees with the tibia protected from
      bending fracture. Of the eight intact knees tested, only one had PCL mid
      substance rupture, one had a partial articular fracture of the tibia below the
      plateau, and six had simple transverse fracture of the tibial metaphysis. Of the
      three PCL-only knees without tibial protection, one had PCL mid substance
      rupture, one had avulsion at the posterior intercondylar attachment point, and
      the last one had a simple oblique fracture of the tibial metaphysis. Of the three
      PCL only knees with tibia protection, two had PCL mid-substance ruptures and the
      third one had an avulsion at the tibial insertion site with partial articular
      fracture of the lateral plateau. Overall, the results of the current study were
      similar to those observed by Viano et al. (1978). The average displacement at
      failure for all PCL related injuries was 17.2+/-2.8 mm for the current study
      (n=6) and 16.2+/-3.9 mm for Viano et al. (1978) (n=4). This value is higher than
      the Injury Assessment Reference Value of 15 mm proposed by Mertz (1984) and used
      in various regulations. Both studies suggest that the existence of the soft
      tissues other than the PCL affect the injury outcome and that the intact knee
      would suffer predominantly tibial metaphyseal fractures possibly due to bending.
      Consequently, it is concluded that the current experimental setup can produce
      isolated PCL injuries but the data available are inadequate to characterize PCL
      tolerance. A Hybrid III knee equipped with a ball bearing knee slider was also
      tested using a pendulum setup. Apart from the initial higher stiffness, the
      overall response of this knee lies within the force-deflection corridors defined
      using the response of the cadaver knees with PCL mid-substance failure.

PMID- 17230263
TI  - Non-injurious and injurious impact response of the human shoulder three
      dimensional analysis of kinematics and determination of injury threshold.
AB  - Seven Post Mortem Human Subjects were submitted to three low velocity impacts
      (v=1.5 m/s) to the right shoulder at three different angles in the horizontal
      plane (-15 degrees , 0 degrees , +15 degrees ). Then, the left shoulder was
      submitted to a purely lateral high velocity impact (v=3, 4, 6 m/s). The load was
      delivered by a 23.4 kg impactor fitted with a rigid rectangular impacting plate.
      Shoulder and thoracic bone structures were equipped with tri-axial accelerometers
      and photographic markers, whose trajectories were tracked in 3D by seven high
      speed cameras. The results were scaled in order to account for the differences
      between the subjects' anthropometry and to define response corridors for the
      evaluation of the dummies' shoulders. Impact forces as well as several shoulder
      deflections were analyzed with respect to each subject's injury survey in order
      to find the most relevant parameters for the prediction of injuries. In the case
      of oblique impacts, slight modifications in the shoulder responses were observed,
      with higher force peaks obtained for the +15 degrees impacts in comparison to the
      0 degrees and -15 degrees impacts. Acromion-to-sternum deflection peak values
      were closely linked with a clavicle fracture, but could not predict other types
      of fracture for which acromion-to-acromion deflection was a better predictor.

PMID- 17230264
TI  - Mechanical Properties of the Shoulder Ligaments under Dynamic Loading.
AB  - Thirty-three fresh human cadaver shoulders were harvested and bone-ligament-bone
      specimens of acromioclavicular joint, coracoclavicular joint and sternoclavicular
      joint were obtained. A test fixture and clamps specifically designed for this
      ligament study and a high-speed Instron machine were used. One quasi-static rate
      (nominally 0.1 %/sec) and two high rates (nominally, high rate 1 = 40,000 %/sec
      and high rate 2 = 15,000 %/sec) were used in this study. In the acromioclavicular
      joint tests, ligament failure was the most common failure mode. Bone fractures
      occurred most often at the clavicle rather than acromion. In the coracoclavicular
      joint tests, the majority of specimens failed at the ligament and bone fractures
      occurred at the coracoid. In the sternoclavicular joint tests, the specimen
      failed at the bone in most cases. In the acromioclavicular joint and
      coracoclavicular joint tests, high rate 2 tests and quasi-static tests had more
      bone fracture cases than high rate 1 tests. Cross sectional area, deflection at
      failure, load at failure, strain at failure, stress at failure and Young's
      modulus of these three shoulder joints were found. The Young's modulus, ultimate
      stress and ultimate load of the three joints were found to be significantly lower
      in the quasi-static rate tests compared to the high rate 2 tests but not
      significantly different between high rate 1 and high rate 2 tests. There are no
      significant relationships between cross-sectional area and age, height or weight,
      nor between the mechanical properties of the shoulder joint and age, height or
      weight.

PMID- 17230265
TI  - Upper extremity interaction with a helicopter side airbag: injury criteria for
      dynamic hyperextension of the female elbow joint.
AB  - This paper describes a three part analysis to characterize the interaction
      between the female upper extremity and a helicopter cockpit side airbag system
      and to develop dynamic hyperextension injury criteria for the female elbow joint.
      Part I involved a series of 10 experiments with an original Army Black Hawk
      helicopter side airbag. A 5(th) percentile female Hybrid III instrumented upper
      extremity was used to demonstrate side airbag upper extremity loading. Two out of
      the 10 tests resulted in high elbow bending moments of 128 Nm and 144 Nm. Part II
      included dynamic hyperextension tests on 24 female cadaver elbow joints. The
      energy source was a drop tower utilizing a three-point bending configuration to
      apply elbow bending moments matching the previously conducted side airbag tests.
      Post-test necropsy showed that 16 of the 24 elbow joint tests resulted in
      injuries. Injury severity ranged from minor cartilage damage to more moderate
      joint dislocations and severe transverse fractures of the distal humerus. Peak
      elbow bending moments ranged from 42.4 Nm to 146.3 Nm. Peak bending moment proved
      to be a significant indicator of any elbow injury (p = 0.02) as well as elbow
      joint dislocation (p = 0.01). Logistic regression analyses were used to develop
      single and multiple variate injury risk functions. Using peak moment data for the
      entire test population, a 50% risk of obtaining any elbow injury was found at 56
      Nm while a 50% risk of sustaining an elbow joint dislocation was found at 93 Nm
      for the female population. These results indicate that the peak elbow bending
      moments achieved in Part I are associated with a greater than 90% risk for elbow
      injury. Subsequently, the airbag was re-designed in an effort to mitigate this as
      well as the other upper extremity injury risks. Part III assessed the redesigned
      side airbag module to ensure injury risks had been reduced prior to implementing
      the new system. To facilitate this, 12 redesigned side airbag deployments were
      conducted using the same procedures as Part I. Results indicate that the re
      designed side airbag has effectively mitigated elbow injury risks induced by the
      original side airbag design. It is anticipated that this study will provide
      researchers with additional injury criteria for assessing upper extremity injury
      risk caused by both military and automotive side airbag deployments.

PMID- 17230266
TI  - Human Neck Finite Element Model Development and Validation against Original
      Experimental Data.
AB  - This study proposes a detailed FEM of a human volunteer's neck and proceeds to an
      original model validation against experimental data recorded with this human
      volunteer. In order to evaluate the new model against existing data a successful
      temporal validation of the model was obtained under frontal, lateral, oblique and
      rear impact. New validation parameters are based on an experimental test
      proceeded in the frequency domain in order to extract the volunteer's Head-Neck
      system's modal characteristics. In depth validation of the head neck FEM is then
      performed by superposing the numerical and experimental frequency response
      function. Model optimisation in the frequency domain permitted after significant
      properties modification to reproduced accurately both, the neck extension mode at
      1.4 Hz and the head retraction mode at 8.8 Hz. Finally the "frequency domain
      optimised" FEM response was superimposed with the temporal corridors provided in
      the literature. It must be mentioned that the model's response in the temporal
      domain remains inside existing corridors after this model optimisation in the
      frequency domain illustrating that the temporal validation is not accurate
      enough. This study proposes a neck model with improved geometry description and
      biofidelity with special attention paid to the retraction mode, a phenomenon
      which is often masked in the temporal domain.

PMID- 17230267
TI  - A Novel Approach for Predicting Human Response from ATD Tests.
AB  - A methodology was developed for predicting the human response from ATD
      (Anthropomorphic Test Device) tests or for improving the biofidelity of the ATD
      response. The ATD response and human response are considered as the output of a
      black box system, from which the relationship between the ATD tests and human
      tests was established using wavelet analysis. Based on the decompositions of both
      responses on a wavelet packet basis, a mapping matrix is built after executing a
      procedure that includes de-noising and compression, energy distribution analysis,
      correlation analysis and regression analysis, and spectral coherence analysis and
      transfer function analysis. With the mapping matrix, an ATD response is modified
      or reconstructed into the corresponding human response. The practical use of the
      methodology was illustrated in the analysis of a series of lateral impact tests
      conducted on a horizontal impulse accelerator with an ATD and human volunteers as
      the test subjects. The predictions from the ATD tests using this method have
      attained significant improvement in biofidelity.

PMID- 17230268
TI  - In vivo measurements of human brain displacement.
AB  - Finite element models are increasingly important in understanding head injury
      mechanisms and designing new injury prevention equipment. Although boundary
      conditions strongly influence model responses, only limited quantitative data are
      available. While experimental studies revealed some motion between brain and
      skull, little data exists regarding the base of the skull. Using magnetic
      resonance images (MRI) of the caudal brain regions, we measured in vivo, quasi
      static angular displacement of the cerebellum (CB) and brainstem (BS) relative to
      skull, and axial displacement of BS at the foramen magnum in supine human
      subjects (N=5). Images were obtained in flexion (7 degrees - 54 degrees ) and
      neutral postures using SPAMM tagging technique (N=47 pairs). Rigid body skull
      rotation angle from neutral posture (theta, degrees) was determined by extracting
      the edge feature points of the skull, and rotating and displacing the coordinates
      in one image until they matched those in the other. Tissue rotation was obtained
      by comparing tag lines in image pairs before and after flexion, and the motion of
      BS and CB were expressed relative to skull rotation and displacement. During
      flexion, the CB rotated in the flexion direction, exceeding the skull rotation,
      but relative BS rotations were negligible. Meanwhile, the BS moved caudally
      toward the foramen magnum. With a flexion angle of 54 degrees , the 95%
      confidence interval for the relative CB rotation was 2.7 degrees - 4.3 degrees ,
      and 0.8 - 1.6mm for the relative BS axial displacement. Albeit quasi-static, this
      study provides important data that can be implemented to create more life-like
      boundary conditions in human finite element models.

PMID- 17230269
TI  - Shear Properties of Brain Tissue over a Frequency Range Relevant for Automotive
      Impact Situations: New Experimental Results.
AB  - This research aims at improving the definition of the shear linear material
      properties of brain tissue. A comparison between human and porcine white and gray
      matter samples was carried out over a new large frequency range associated with
      both traffic road and non-penetrating ballistic impacts. Oscillatory experiments
      were performed by using an original custom-designed oscillatory shear testing
      device. The findings revealed that no significant difference occured between the
      linear viscoelastic behavior of the porcine and the human brain tissue. On the
      average, the storage modulus (G') and the loss modulus (G") of the white matter
      increased respectively from 2.1 +/- 0.9 kPa to 16.8 +/- 2.0 kPa and from 0.4 +/-
      0.2 kPa to 18.7 +/- 2.3 kPa between 0.1 and 6300 Hz at 37 degrees C. In addition,
      the gray and white matter behaviors seemed to be similar at small strains. The
      reliability of the data and the robustness of the experimental protocol were
      checked using a standard rheometer (Bohlin C-VOR 150). A good agreement was found
      between the data obtained in the frequency and time field. As a result, the
      linear relaxation modulus was determined over an extensive time range (from 10(
      5) s to 300 s). In a first approach, the nonlinear behavior of brain tissue was
      studied using stress relaxation tests. Brain tissue showed significant shear
      softening for strains above 1% and the time relaxation behavior was independent
      of the applied strain. On this basis, a visco-hyperelastic model was proposed
      using the generalized Maxwell model and the Ogden hyperelastic model. These
      models respectively describe the linear relaxation modulus and the strain
      dependence of the shear stress.

PMID- 17230270
TI  - The influence of surrogate blood vessels on the impact response of a physical
      model of the brain.
AB  - Cerebral blood vessels are an integral part of the brain and may play a role in
      the response of the brain to impact. The purpose of this study was to quantify
      the effects of surrogate vessels on the deformation patterns of a physical model
      of the brain under various impact conditions. Silicone gel and tubing were used
      as surrogates for brain tissue and blood vessels, respectively. Two aluminum
      cylinders representing a coronal section of the brain were constructed. One
      cylinder was filled with silicone gel only, and the other was filled with
      silicone gel and silicone tubing arranged in the radial direction in the
      peripheral region. An array of markers was embedded in the gel in both cylinders
      to facilitate strain calculation via high-speed video analysis. Both cylinders
      were simultaneously subjected to a combination of linear and angular acceleration
      using a two-segment pendulum. Marker motion was tracked, and maximum shear strain
      (MSS) and maximum principal strain (MPS) were calculated using markers clustered
      in groups of three. Four test series were conducted. Peak angular acceleration
      varied from 2,600 to 26,000 rad/s2, and peak angular speed varied from 17 to 29
      rad/s. For a given impact condition, the test-to-test variation of these values
      was less than 5.5%. For all clusters, the peak MSS and peak MPS for both physical
      models were less than 26% and 32%, respectively. For 90% of the cluster
      locations, the absolute value of the difference in peak MSS and peak MPS between
      the physical models was 4% and 6%, respectively. In the physical model with
      tubing, strain tended to decrease in the periphery (near to the tubing), while it
      tended to increase toward the center (away from the tubing). Strain amplitudes
      were found to be sensitive to the peak angular speeds. In general, this study
      suggests that the vasculature could influence the deformation response of the
      brain.

PMID- 17230271
TI  - Mechanical properties and anthropometry of the human infant head.
AB  - The adult head has been studied extensively and computationally modeled for
      impact, however there have been few studies that attempt to quantify the
      mechanical properties of the pediatric skull. Likewise, little documentation of
      pediatric anthropometry exists. We hypothesize that the properties of the human
      pediatric skull differ from the human adult skull and exhibit viscoelastic
      structural properties. Quasi-static and dynamic compression tests were performed
      using the whole head of three human neonate specimens (ages 1 to 11 days old).
      Whole head compression tests were performed in a MTS servo-hydraulic actuator.
      Testing was conducted using nondestructive quasi-static, and constant velocity
      protocols in the anterior-posterior and right-left directions. In addition, the
      pediatric head specimens were dropped from 15cm and 30cm and impact force-time
      histories were measured for five different locations: vertex, occiput, forehead,
      right and left parietal region. The compression stiffness values increased with
      an increase in velocity but were not significantly different between the anterior
      posterior and right-left directions. Peak head acceleration during the head
      impact tests did not significantly vary between the five different impact
      locations. A three parameter model that included damping represented the
      pediatric head impact data more accurately than a simple mass-spring system. The
      compressive and impact stiffness of the pediatric heads were significantly more
      compliant than published adult values. Also, infant head dimensions, center of
      gravity and moment of inertia (Iyy) were determined. The CRABI 6-month dummy
      impact response was similar to the infant cadaver for impacts to the vertex,
      occiput, and forehead but dramatically stiffer in lateral impacts. These
      pediatric head anthropomorphic, compression, and impact data will provide a basis
      to validate whole head models and compare with ATD performance in similar
      exposures.

PMID- 17230272
TI  - Cervical spine geometry in the automotive seated posture: variations with age,
      stature, and gender.
AB  - In the mid 1970s, UMTRI investigated the biomechanical properties of the head and
      neck using 180 "normal" adult subjects selected to fill eighteen subject groups
      based on age (young, mid-aged, older), gender, and stature (short, medium, and
      tall by gender). Lateral-view radiographs of the subjects' cervical spines and
      heads were taken with the subjects seated in a simulated automotive neutral
      posture, as well as with their necks in full-voluntary flexion and full-voluntary
      extension. Although the cervical spine and lower head geometry were previously
      measured manually and documented, new technologies have enabled computer
      digitization of the scanned x-ray images and a more comprehensive and detailed
      analysis of the variation in cervical spine and lower head geometry with subject
      age, stature, and gender. After scanning the radiographic images, 108 skeletal
      landmarks on the cervical vertebrae and 10 head landmarks were digitized. The
      resulting database of cervical spine and head geometry was used to study cervical
      spine curvature, vertebral dimensions, and head/neck orientation as functions of
      age, gender, and stature. The data were used to characterize neutral posture
      cervical spine curvatures using two methods: a curvature index and Bezier spline
      functions. Lateral-view vertebral dimensions were also calculated for each
      subject, and a cascading series of equations was developed to estimate vertebral
      size and shape for a selected age, stature, and gender. The orientation of the
      cervical spine was defined using a neck chord angle, where the neck chord was
      varied to use different anatomical landmarks and estimates of joint centers for
      the top and bottom of the neck chord. Results from the study have been
      incorporated into a MS-Access based software package that allows researchers and
      modelers to generate cervical spine geometries for occupants of a specified age,
      gender, and stature. The program allows selection of individual occupants from
      the database that meet age, stature, gender, or curvature criteria, or creation
      of a composite cervical spine geometry representative of the selected age,
      gender, and stature. This tool will allow researchers to configure and vary
      cervical spine geometry in computer models and experimental test setups used to
      study head and neck impact response and injury risk.

PMID- 17230273
TI  - Effect of Head-Neck Position on Cervical Facet Stretch of Post Mortem Human
      Subjects during Low Speed Rear End Impacts.
AB  - The purpose of this study was to determine the effect of head-neck position on
      cervical facet stretch during low speed rear end impact. Twelve tests were
      conducted on four Post Mortem Human Subjects (PMHS) in a generic bucket seat
      environment. Three head positions, namely Normal (neutral), Zero Clearance
      between the head and head restraint, and Body Forward positions were tested. A
      high-speed x-ray system was used to record the motion of cervical vertebrae
      during these tests. Results demonstrate that: a) The maximum mean facet stretch
      at head restraint contact occurs at MS4 and MS5 for the Body Forward condition,
      b) The lower neck flexion moment, prior to head contact, shows a non-linear
      relationship with facet stretch, and c) "Differential rebound" during rear end
      impact increases facet stretch.

PMID- 17230274
TI  - In vivo cervical facet capsule distraction: mechanical implications for whiplash
      and neck pain.
AB  - While extensive research points to mechanical injury of the cervical facet joint
      as a mechanism of whiplash injury, findings remain speculative regarding its
      potential for causing pain. The purpose of this study was to examine the
      relationship between facet joint distraction, capsular ligament strain, cellular
      nociceptive responses, and pain. A novel rat model of in vivo facet joint injury
      was used to impose C6/C7 joint distraction in separate studies of subcatastrophic
      and physiologic vertebral distraction, as well as sham procedures. A common
      clinical measure of behavioral hypersensitivity (allodynia) was measured for 14
      days after injury, as quantification of resulting pain symptoms. Also, on day 14,
      spinal activation of microglia and astrocytes was quantified to examine the
      potential role of glial activation as a physiologic mechanism of facet-mediated
      painful injury. Vertebral distractions of 0.90+/-0.53 mm across the rat facet
      joint reliably produced symptoms of persistent pain. Allodynia results showed
      immediate and sustained behavioral sensitivity following subcatastrophic
      vertebral distractions; pain symptoms were significantly greater (p<0.008) than
      those for other injury groups. Further, spinal astrocytic activation was also
      greater (p=0.049) for subcatastrophic injuries compared to lower distraction
      magnitudes. The mean maximum principal strain in the capsular ligament for joint
      distractions of 0.57+/-0.11 mm was 27.7+/-11.9%. Findings suggest that facet
      capsule strains comparable to those previously reported for whiplash kinematics
      and subcatastrophic failures of this ligament have the potential to produce pain
      symptoms and alter one element of nociception. Results further suggest that a
      mechanical threshold likely exists for painful joint distraction, providing
      behavioral and physiologic evidence of the cervical facet joint's mechanical
      injury as a source of neck pain.

PMID- 17230275
TI  - Variation of neck muscle strength along the human cervical spine.
AB  - The aim of this study was to describe and explain the variation of neck muscle
      strength along the cervical spine. A three-dimensional model of the head-neck
      complex was developed to test the hypothesis that the moment-generating capacity
      of the neck musculature is lower in the upper cervical spine than in the lower
      cervical spine. The model calculations suggest that the neck muscles can protect
      the lower cervical spine from injury during extension and lateral bending. The
      maximum flexor moment developed in the lower cervical spine was 2 times higher
      than that developed in the upper spine. The model also predicted that the neck
      musculature is 30% stronger in the lower cervical spine during lateral bending.
      Peak compressive forces (up to 3 times body weight) were higher in the lower
      cervical spine. These results are consistent with the clinical finding that
      extension loading of the neck often leads to injuries in the upper cervical
      spine. Analysis of the model results showed that neck flexor strength was greater
      in the lower cervical spine because of the relatively large size of the
      sternocleidomastoid muscle. The hyoid muscles developed significant flexor
      moments about the joints of the upper cervical spine, as these muscles had
      relatively large flexor moment arms; however, this effect was offset by the
      action of the sternocleidomastoid, which exerted a large extensor moment in the
      upper spine. Lateral bending strength of the neck muscles was governed by
      geometry (i.e., moment arms) rather than by muscle size.

PMID- 17230276
TI  - Gradation of Neck Muscle Responses and Head/Neck Kinematics to Acceleration and
      Speed Change in Rear-end Collisions.
AB  - Recent epidemiological evidence shows that the potential for whiplash injury
      varies with both the average acceleration and speed change of a rear-end
      collision. The goal of this study was to examine the gradation of neck muscle
      responses and the head and neck kinematics to rear-end collision pulses in which
      the acceleration and speed change were independently varied. Thirty subjects
      (15F, 15M) underwent 36 consecutive rear-end collisions consisting of three
      different average accelerations (a = 0.5, 0.9 and 1.3 g) and three different
      speed changes (Deltav = 0.25, 0.50 and 0.75 m/s). Onset and amplitude of the
      sternocleidomastoid (SCM) and cervical paraspinal (PARA) muscle responses were
      measured using surface electromyography. Kinematic measures included linear and
      angular accelerations and displacements of the head and torso. The results showed
      that the amplitude of the muscle and kinematics responses was graded to both
      collision acceleration and speed change. The magnitude of early peaks in the
      head/neck kinematics correlated more strongly with collision acceleration (r(2) =
      0.63 to 0.69), whereas the magnitude of later kinematic peaks correlated more
      strongly with collision speed change (r(2) = 0.59 to 0.95). Onset of the SCM
      muscle response correlated only weakly with collision acceleration and speed
      change (r(2) </= 0.07). A collision pulse descriptor obtained by multiplying
      average acceleration and speed change (aDeltav) yielded the strongest and most
      consistent correlations with neck muscle (r(2) = 0.48 to 0.58) and head/neck
      kinematic responses (r(2) = 0.78 to 0.94). This measure of collision severity is
      also consistent with the recent epidemiological evidence that whiplash symptom
      intensity and duration increases with both average acceleration and speed change.

PMID- 17230277
TI  - WorldSID Dummy Head-Neck Biofidelity Response.
AB  - Accident studies indicate that serious neck injuries are generally infrequent in
      side crashes. However, given the rapid changes in side impact protection
      technology, such as side airbags and curtain systems, the nature of head-neck
      interactions is likely to change. Consequently, the newest generation of
      anthropomorphic test devices for side impact should provide realistic prediction
      of the head-neck kinematics and include meaningful measurements related to risk
      of head and neck injury. The WorldSID dummy has been assessed against a set of
      five test conditions that have been used to define biofidelity impact response
      targets. Three of the five test conditions are recommended by ISO TR9790 (ISO
      1997), the NBDL 7.2 G, 6.9 m/s lateral sled impact reported by Ewing et al.
      (1977) and Wismans et al. (1986) , the Patrick and Chou lateral, 6.7 G 5.8 m/s
      (1976) and Tarriere lateral 12.2 g, 6,1 m/s sled impact (ISO 1997). Due to its
      expected loading environment, the dummy neck performance has also been evaluated
      for neck bending in frontal flexion and extension (Mertz and Patrick, 1971). The
      5th test condition is the NBDL 45 degrees frontal-oblique sled test (Wismans
      1986, Philippens 2004). The latter and two of the ISO TR9790 test conditions form
      the basis of the draft IHRA requirements for evaluating side impact dummy
      biomechanical responses. The paper reports on the findings of the assessment of
      the WorldSID pre-production dummy. The Mertz and Patrick OC moment-head angle
      corridor is used as supplemental requirement for frontal flexion-extension. The
      biofidelity requirements contain both kinematic and dynamic response targets. The
      neck has a good performance for NBDL lateral and Tarriere requirements, and the
      Mertz OC moment-flexion angle. The performance for the Patrick and Chou, the NBDL
      oblique test conditions and the Mertz OC moment extension angle are fair to
      marginal. The repeatability performance of the dummy was found to be good for all
      lateral and most oblique test parameters. The neck design does not allow much
      more further optimization without fundamental changes.

PMID- 17230278
TI  - A Theoretical Math Model for Projecting AIS3+ Thoracic Injury for Belted
      Occupants in Frontal Impact.
AB  - A theoretical math model was created to assess the net effect of aging
      populations versus evolving system designs from the standpoint of thoracic injury
      potential. The model was used to project the next twenty-five years of thoracic
      injuries in Canada. The choice of Canada was topical because rulemaking for CMVSS
      208 has been proposed recently. The study was limited to properly-belted, front
      outboard, adult occupants in 11-1 o'clock frontal crashes. Moreover, only AIS3+
      thoracic injury potential was considered. The research consisted of four steps.
      First, sub-models were developed and integrated. The sub-models were made for
      numerous real-world effects including population growth, crash involvement, fleet
      penetration of various systems (via system introduction, vehicle production, and
      vehicle attrition), and attendant injury risk estimation. Second, existing NASS
      data were used to estimate the number of AIS3+ chest-injured drivers in Canada in
      2001. This served as data for model validation. Third, the projection model was
      correlated favorably with the 2001 field estimate. Finally, for the scenario that
      2004-2030 model-year systems would perform like 2000-2003 model-year systems, a
      projection was made to estimate the long-term effect of eliminating designs that
      would not comply with the proposed CMVSS 208. The 2006-2030-projection result for
      this scenario: 764 occupants would benefit from the proposed regulation. This
      projection was considered to be conservative because future innovation was not
      considered, and, to date, the fleet's average chest deflections have been
      decreasing. The model also predicted that, through 2016, the effect of improving
      system performance would be more influential than the population-aging effect;
      thereafter, the population-aging effect would somewhat counteract the effect of
      improving system performance. This theoretical math model can provide insights
      for both designers and rule makers.

PMID- 17230279
TI  - Predictors of pediatric abdominal injury risk.
AB  - Although previous research has linked poor seat belt fit to abdominal organ
      injury for children, few have studied the pattern of pediatric abdominal injuries
      and its relationship to key characteristics beyond this primary association. In
      this study, data were obtained from a probability sample of 19,125 children,
      representing 243,540 children, under age 16 years who were enrolled in an on
      going crash surveillance system which links insurance claims data to validated
      telephone survey and crash investigation data. The risk of AIS2+ abdominal injury
      was estimated for various crash, restraint, vehicle and child correlates and
      multivariate logistic regression was used to identify the relative importance of
      these predictors. Children 4-8 years of age were at the highest risk of abdominal
      injury: they were 24.5 times and 2.6 times more likely to sustain an AIS2+
      abdominal injury than those 0-3 years and 9-15 years, respectively. The injury
      risk for children 4-8 years of age was 6 and 10 times higher in passenger cars
      and SUVs, respectively, compared to minivans. No reduction in abdominal injury
      risk was seen with rear seating. The role of direction of impact on injury risk
      varied by child age indicating diverse injury sources influenced by developmental
      differences and changes in restraint practices among the age groups. The data
      suggested a trade-off between head/face injury and abdominal injury: for those
      restrained in vehicle seat belts in rear seats, those with an AIS2+ head/face
      injury were nearly 90% less likely to sustain an abdominal injury than those
      without a head/face injury. These findings suggest mechanistic hypotheses to be
      tested with additional in-depth data.

PMID- 17230280
TI  - Thoracic response to dynamic, non-impact loading from a hub, distributed belt,
      diagonal belt, and double diagonal belts.
AB  - This paper presents thoracic response corridors developed using fifteen post
      mortem human subjects (PMHS) subjected to single and double diagonal belt,
      distributed, and hub loading on the anterior thorax. We believe this is the first
      study to quantify the force-deflection response of the same thorax to different
      loading conditions using dynamic, non-impact, restraint-like loading. Subjects
      were positioned supine on a table and a hydraulic master-slave cylinder
      arrangement was used with a high-speed materials testing machine to provide
      controlled chest deflection at a rate similar to that experienced by restrained
      PMHS in a 48-km/h sled test. All loading conditions were tested at a nominally
      non-injurious level initially. When the battery of non-injurious tests was
      completed, a single loading condition was used for a final, injurious test
      (nominal 40% chest deflection). To minimize the influence of repeated testing,
      all subjects were preconditioned prior to each loading condition using 10 cycles
      of a 1-Hz sine wave, and the order in which the loading conditions were tested
      was varied across subjects. Thoracic response was characterized using the
      deflection at the midline of the sternum and a load cell mounted between the
      subject and the loading table. Responses were defined by cross-plotting the mid
      sternal deflection (normalized to 50(th) male) and the posterior force (scaled to
      a 45-year-old, 50(th) male based on size and modulus) and then forming a +/-1
      standard-deviation corridor that considered the variance in both force and
      deflection. Corridors were developed to a deflection level of 20% of the 50(th)
      percentile male's external chest depth. The distributed loading condition
      generated the stiffest response (3.33 kN at 4.6 cm), followed by the double
      diagonal belt condition (3.18 kN at 4.6 cm), the single diagonal belt (2.28 kN at
      4.6 cm) and the hub (1.14 kN at 4.6 cm).

PMID- 17230282
TI  - Surgical interruption of pelvic nerve pathways in dysmenorrhea: a systematic
      review of effectiveness.
AB  - OBJECTIVES: To assess the effectiveness of surgical interruption of pelvic nerve
      pathways in primary and secondary dysmenorrhea. Data sources. The Cochrane
      Menstrual Disorders and Subfertility Group Trials Register (9 June 2004), CENTRAL
      (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to Nov. 2003), EMBASE (1980
      to Nov. 2003), CINAHL (1982 to Oct. 2003), MetaRegister of Controlled Trials, the
      citation lists of review articles and included trials, and contact with the
      corresponding author of each included trial. REVIEW METHODS: The inclusion
      criteria were randomized controlled trials of uterosacral nerve ablation or
      presacral neurectomy (both open and laparoscopic procedures) for the treatment of
      dysmenorrhea. The main outcome measures were pain relief and adverse effects. Two
      reviewers extracted data on characteristics of the study quality and the
      population, intervention, and outcome independently. RESULTS: Nine randomized
      controlled trials were included in the systematic review. There were two trials
      with open presacral neurectomy; all other trials used laparoscopic techniques.
      For the treatment of primary dysmenorrhea, laparoscopic uterosacral nerve
      ablation at 12 months was better when compared to a control or no treatment (OR
      6.12; 95% CI 1.78-21.03). The comparison of laparoscopic uterosacral nerve
      ablation with presacral neurectomy for primary dysmenorrhea showed that at 12
      months follow-up, presacral neurectomy was more effective (OR 0.10; 95% CI 0.03
      0.32). In secondary dysmenorrhea, along with laparoscopic surgical treatment of
      endometriosis, the addition of laparoscopic uterosacral nerve ablation did not
      improve the pain relief (OR 0.77; 95% CI 0.43-1.39), while presacral neurectomy
      did (OR 3.14; 95% CI 1.59-6.21). Adverse events were more common for presacral
      neurectomy than procedures without presacral neurectomy (OR 14.6; 95% CI 5-42.5).
      CONCLUSION: The evidence for nerve interruption in the management of dysmenorrhea
      is limited. Methodologically sound and sufficiently powered randomized controlled
      trials are needed.

PMID- 17230283
TI  - Accuracy of HPV testing of vaginal smear obtained with a novel self-sampling
      device.
AB  - BACKGROUND: Most of women diagnosed as having cervical cancer have not
      participated in organized cytological screening. Aim. A study was conducted to
      evaluate the accuracy of human papilloma virus testing by self-collected vaginal
      samples in comparison to regular cytological screening. The agreement of hybrid
      capture 2 assay and polymerase chain reaction assay for detection of human
      papilloma virus DNA in self-collected vaginal samples and clinician-obtained
      cervical smears was investigated. METHOD: Forty-three women aged 23-58 years
      admitted for further examination due to previous positive cytology in the
      organized screening participated in self-collecting of vaginal samples with a
      novel self-sampling device. During the visit a clinician also collected a
      cervical smear using a cytobrush. The vaginal samples collected with the self
      sampling device were analyzed for high-risk human papilloma virus with the hybrid
      capture 2 assay technique and the cervical smears were Pap-stained, examined
      cytologically and after that reanalyzed for human papilloma virus DNA using a
      polymerase chain reaction assay. RESULT: The vaginal samples were positive for
      high-risk human papilloma virus in 37% of the cases using hybrid capture 2 assay.
      Twelve of the 43 Pap smears showed positive cytology (ASCUS-CIN 3), of which 4
      showed CIN 2-3. When polymerase chain reaction assay was performed, human
      papilloma virus DNA was detected in 40% of the glass slides. The agreement
      between cytology and the two human papilloma virus testing techniques was 67-74%
      (kappa 0.27-0.45) and the agreement between the two human papilloma virus tests
      was 70% (kappa 0.36). CONCLUSION: Testing for high-risk human papilloma virus can
      identify more women at risk of developing cervical cancer than cytology
      irrespective of the sampling method. Furthermore, offering a self-sampling device
      for collection of vaginal smear seems to be a useful screening tool for cervical
      cancer among women not responding to an invitation for smear sampling.

PMID- 17230284
TI  - Pregnancy outcome of uterine arterial embolization followed by selective
      hysteroscopic removal of a placental polyp.
AB  - OBJECTIVE: To evaluate the pregnancy outcome of uterine arterial embolization
      followed by selective hysteroscopic removal of a placental polyp. METHODS:
      Thirteen patients of placental polyp with abundant blood flow, which was
      diagnosed by ultrasound with color Doppler imaging, were studied. They underwent
      uterine arterial embolization followed by selective hysteroscopic removal of the
      polyp. Uterine arterial embolization was carried out using an absorbable gelatin
      sponge. Selective removal via hysteroscopy was performed on the following day,
      using the cutting loop with or without electrical stimulation. The polyp was
      gradually resected to the level of the surrounding endometrium. RESULTS: Complete
      removal of the placental polyp was achieved in all patients. The presence of
      placental polyp was confirmed by pathologic examination. The operative time
      ranged from 20 to 53 min. In all cases, no complications were noted and the
      bleeding was minimal during and immediately after the procedure. Postoperative
      ultrasound demonstrated a uterine cavity free of residual mass in each case. The
      seven patients with complete gestation gave birth to health babies. No recurrence
      of placental polyp was observed. CONCLUSIONS: Selective removal directed via
      hysteroscopy after reduction of blood supply by uterine arterial embolization
      provides a safe and effective method to minimize bleeding, and can preserve
      future fertility and successful uneventful pregnancies in the treatment of
      placental polyp with abundant blood flow.

PMID- 17230285
TI  - Maternal mid-arm circumference and other anthropometric measures of adiposity in
      relation to infant birth size among Zimbabwean women.
AB  - BACKGROUND: To examine relationships between maternal anthropometric measures in
      Zimbabwean women and indices of infant birth size. METHODS: We conducted a cross
      sectional study of pregnant women admitted for labor and delivery at the Harare
      Maternity Hospital from July 1998 to March 1999. The study population was
      comprised of 498 participants who delivered singleton infants. Anthropometric
      measures (height, weight, and mid-arm circumference) were taken during
      participants' postpartum hospital stay. Logistic regression and least-squares
      regression procedures were used to assess the association of maternal measures
      with infant size. RESULTS: Women in the highest weight quartile (>67 kg) were 58%
      less likely to have a low-birth-weight infant when compared to women in the
      lowest quartile (<57 kg) (OR = 0.42, 95% CI 0.19-0.90). Women in the highest body
      mass index quartile were 75% less likely to have a low-birth-weight infant
      compared to women in the lowest quartile (>27 versus <23 kg/m2: OR = 0.25, 95%CI
      0.10-0.60). Similar trends were seen for risk of low birth weight in relation to
      mid-arm circumference. Maternal mid-arm circumference was most strongly related
      with the four infant size indices measured. Each unit increase in maternal mid
      arm circumference resulted in a 36.1-g increase in infant birth weight (p<0.001).
      In general, women who were heavier at the time of delivery were less likely to
      have a low-birth-weight infant than women who were lighter. CONCLUSIONS: In areas
      where food security is a public health concern, as it is in most parts of the
      developing world, pregnant women may not be meeting their own nutritional needs
      and those of their fetus.

PMID- 17230286
TI  - A survey of knowledge, attitude and practice of malaria management among pregnant
      women from two health care facilities in Nigeria.
AB  - BACKGROUND: Malaria remains one of the most important causes of maternal and
      child morbidity and mortality in sub-Saharan Africa, despite the availability of
      effective interventions. The objective of this study was to assess the knowledge,
      attitude and practice of malaria management among pregnant women attending
      antenatal clinics in Nigeria. METHODS: A cross-sectional study was undertaken on
      a sample of 867 pregnant women attending antenatal clinics in 2 health care
      facilities in Edo State, Nigeria, using a self-administered questionnaire.
      RESULTS: Of the respondents, 87% said that they had undergone at least 1 episode
      of malaria during their current pregnancy. Most respondents (89%) attributed
      malaria to bites from infected mosquitoes, while 75% consider malaria an
      important health risk during pregnancy. However, knowledge of the consequences of
      malaria during pregnancy was poor, especially the risk posed to the fetus.
      Overall, the mean knowledge score on a scale of '0-7' was 3.5 (median 4.0).
      Respondents had poor belief in the effectiveness and use of insecticide-treated
      bed nets and intermittent preventive therapy, in preventing malaria during
      pregnancy. CONCLUSIONS: This study has revealed that malaria is perceived as a
      common health problem among pregnant women attending these 2 health care
      facilities, and that knowledge, attitude and practice of its management is poor.
      Efforts should be made to improve anti-malarial intervention during pregnancy, to
      ensure that the goals of the Roll Back Malaria Initiative are achieved in
      Nigeria.

PMID- 17230287
TI  - Curve of amniotic fluid index measurements in low-risk pregnancy.
AB  - OBJECTIVES: To establish a curve of amniotic fluid index [AFI] measurements from
      the 20th to the 42nd week of pregnancy. METHODS: A prospective and descriptive
      study was performed, in which an independent sample of 2,868 low-risk pregnant
      women were studied using routine ultrasound, including fetal biometry and
      measurement of AFI. Data were analysed using multiple linear regression, and
      constructing a curve using 2.5th, 10th, 50th, 90th and 97.5th percentiles of the
      AFI measurements, according to gestational age, and after submitting values to
      smoothing process using quadratic polynomial adjustment. RESULTS: There was a
      significant variation in AFI measurements at the different gestational ages. The
      50th percentile remained practically constant at approximately 150 mm between the
      20th and 33rd week, after which there was a decline in volume, which became
      evident after the 38th week. At the 40th week, the 10th percentile was around 62
      mm and the 2.5th percentile around 33 mm. CONCLUSIONS: The curve of percentiles
      of AFI measurements in low-risk pregnant women showed significant decrease with
      gestational age, especially after the 33rd week. These data should be validated
      for a diagnosis of increased or decreased volumes of amniotic fluid at specific
      gestational ages.

PMID- 17230288
TI  - Perceptions and attitudes of pregnant women towards caesarean section in urban
      Nigeria.
AB  - OBJECTIVES: To determine the perceptions and attitudes towards caesarean section
      [CS] among women attending maternity care at the University of Benin Teaching
      Hospital in Nigeria. METHODS. Some 413 consecutive women, attending antenatal
      care in the hospital, were interviewed with a structured questionnaire that
      solicited information on their socio-demographic characteristics, their previous
      pregnancy and delivery history, and their knowledge and attitudes towards CS.
      Additional focus group discussions and in-depth interviews were held with women
      who recently underwent CS in the hospital, to gain further insights into
      attitudes and perception about CS in the women. RESULTS: The women had good
      knowledge of CS; however, only 6.1% were willing to accept CS as a method of
      delivery, while 81% would accept CS if needed to save their lives and that of
      their babies. Up to 12.1% of women would not accept CS under any circumstances.
      Logistic regression showed that women's low level of education, and past
      successful vaginal and instrumental deliveries, were most likely to be associated
      with women's non-acceptance of indicated caesarean section. Further analysis
      showed that this was mainly due to inaccurate cultural perceptions of labour and
      caesarean section in the cohort of women. CONCLUSION: There is a need for
      programs to increase women's and community understanding and perceptions of CS as
      a method of delivery in Nigeria.

PMID- 17230289
TI  - Avoiding manual removal of placenta: evaluation of intra-umbilical injection of
      uterotonics using the Pipingas technique for management of adherent placenta.
AB  - BACKGROUND: Manual removal of placenta is performed in 1-3% of cases, and whilst
      a well established and relatively safe procedure, it is not without
      complications, which include infection, hemorrhage, uterine rupture, and
      occasional maternal death. METHODS: A three-arm randomized controlled trial of 50
      IU Syntocinon (in 30 ml N saline) versus 800 mcg misoprostol (in 30 ml N saline)
      versus 30 ml N saline alone (control), injected into the placental bed via the
      umbilical vein using the Pipingas method. A group sequential research model
      (triangular test: PEST4) was adopted to minimize the sample size, as retained
      placenta is a relatively uncommon condition. RESULTS: No significant difference
      in the rate of manual removal was observed between the control and Syntocinon
      groups. On triggering the automatic stopping rule for this arm of the trial all
      subsequent cases recruited were allocated to receive either Syntocinon or
      misoprostol. After a total of 54 cases a significant reduction in manual removal
      of placenta was observed in the misoprostol group, triggering the automatic
      stopping rule and terminating the trial. CONCLUSION: Misoprostol (800 mcg)
      dissolved in 30 ml N saline and administered by intraumbilical injection using
      the Pipingas technique significantly reduces the need for manual removal for
      retained adherent placenta, whereas Syntocinon has similar effectiveness to
      injection of N saline alone.

PMID- 17230290
TI  - Attempted vaginal versus planned cesarean delivery in 195 breech first twin
      pregnancies.
AB  - BACKGROUND: To compare neonatal and maternal outcomes for breech first twins
      according to whether vaginal or cesarean delivery was planned and to verify that
      in appropriate selected cases, attempted vaginal delivery is a reasonable choice.
      METHODS: A retrospective study of all twin pregnancies with the first twin in
      breech position and gestational age at least 35 weeks at birth at two French
      university hospital centers from January 1994 through December 2000. The primary
      outcome was a combined indicator of neonatal mortality and severe morbidity, as
      defined by one or more of the following: death before discharge, admission to
      neonatal intensive care unit, 5-minute Apgar score <7, cord blood pH <7.10, or
      birth trauma. RESULTS: Cesarean delivery was planned for 71 (36.4%) patients, and
      attempted vaginal delivery for 124 (63.6%), 59 (47.6%) of whom were delivered
      vaginally and 65 (52.4%) by cesarean during labor. Neither the combined negative
      outcome indicator nor neonatal mortality differed significantly for either twin
      or either group. There were no significant differences in maternal mortality or
      morbidity between the two groups. The frequency of deep vein thrombophlebitis or
      pulmonary embolism requiring anticoagulant therapy was significantly higher in
      the planned cesarean group [3/71 (4.2%) versus 0/124; p=0.047]. CONCLUSION: When
      appropriate criteria are used to decide mode of delivery, a careful intrapartum
      protocol is followed, and an experienced obstetrician, midwife, and
      anesthesiologist are in attendance, attempted vaginal delivery is a reasonable
      option for first twins in breech position.

PMID- 17230291
TI  - Primary hyperparathyroidism is common in postmenopausal women with forearm
      fracture and low bone mineral density.
AB  - OBJECTIVE: The most common etiologies of osteoporosis in women are estrogen
      deficiency and, later on in life, the functional changes caused by aging. There
      are, however, numerous causes of secondary bone loss. Little is known about the
      prevalence of concomitant disease in women with distal forearm fracture, which is
      the most common of the classical osteoporotic fractures. METHOD: Postmenopausal
      healthy women between 45 and 65 years of age with a forearm fracture were invited
      to join a prospective randomized study evaluating the effect of physical training
      on bone mineral density. The main inclusion criteria were previous forearm
      fracture and BMD T-score in the interval -1 to -3.0. Of the 167 postmenopausal
      women with a forearm fracture, 23% had a normal BMD, 59% had osteopenia, and 18%
      had osteoporosis. RESULTS: Of the 119 patients meeting the BMD criteria for
      inclusion, one patient was found to have sprue, two were diagnosed with
      thyreotoxicos, and eight had primary hyperparathyroidism. The prevalence of
      primary hyperparathyroidism in this population was 6.7%, and thus three times
      higher than that previously observed in healthy Swedish postmenopausal women.
      CONCLUSION: The data suggest an increased prevalence of primary
      hyperparathyroidism in women with forearm fracture and low bone mass, and imply
      the importance of basic laboratory screening in this population.

PMID- 17230292
TI  - Menstrual disorders and associated factors among adolescent girls visiting a
      youth clinic.
AB  - BACKGROUND: Menstrual disturbances are common among teenagers and are often
      explained by immaturity of the hypothalamic-pituitary-gonadal axis. However,
      little is known about the underlying causes. The aim of this study was to
      evaluate endocrine mechanisms of menstrual disturbances and associated factors
      among adolescent girls visiting a Swedish youth clinic. METHODS. All adolescent
      girls visiting the youth clinic during a five-year period due to menstrual
      disturbances, except those with primary amenorrhea, were included in this
      retrospective study. These 203 girls were evaluated in a standardized manner by
      the same gynecologist. One third also met a psychologist and/or a dietician at
      the clinic. RESULTS: Secondary amenorrhea was diagnosed in 117 girls (58%) and
      oligomenorrhea in 86 girls (42%). Menarcheal age was 13 in both groups.
      Hypothalamic inhibition of the gonadal axis was more frequent in the girls with
      secondary amenorrhea, whereas a hyperandrogenic hormonal pattern as a feature of
      polycystic ovary syndrome was more common in the oligomenorrheic girls. Different
      types of eating disorders were diagnosed in 68% of the amenorrheic girls and in
      38% of the oligomenorrheic girls. CONCLUSIONS: We found hypothalamic amenorrhea
      and hyperandrogenism to be frequent endocrine mechanisms of menstrual disorders
      in teenagers. Concomitant eating disorder was highly frequent and secondary
      amenorrhea was associated with anorectic behavior. It is important to evaluate
      endocrine patterns and eating behavior in adolescents with menstrual disturbances
      to ensure adequate medical care and treatment.

PMID- 17230293
TI  - Risk factors for abdominal scar endometriosis after obstetric hysterotomies: a
      case-control study.
AB  - OBJECTIVE: To identify risk factors that are associated with the development of
      scar endometriosis after obstetric hysterotomies. The hypothesis is that early
      hysterotomy in pregnancy (before 22nd week) is the main risk factor for the
      development of scar endometriosis. METHODS: The authors conducted a case-control
      study between April 2000 and June 2003. A total of 117 women were selected,
      including 39 cases and 78 controls. Exposure and confounding variables were
      measured by a standardized questionnaire, which included sociodemographic
      characteristics, reproductive/physiologic history, past pathological history,
      history of obstetric surgeries, family history, and social history. The odds
      ratio (OR) and its 95% confidence interval (CI) were calculated using bivariate
      analysis for each possible risk factor. These estimates were obtained by
      multivariate analysis using unconditional logistic regression. Tests were made to
      assess the fit of the final model. RESULTS: In the multivariate analysis,
      positive associations were observed between scar endometriosis and hysterotomy
      type (early versus late: OR = 42.99; CI 8.77-210.81), amount of the menstrual
      blood flow (heavy versus light/normal: OR = 11.97; CI 2.35-60.82), and alcoholic
      consumption (yes versus no: OR = 5.31; CI 1.22-23.11). Negative association was
      observed between scar endometriosis and parity (OR = 0.61; CI 0.31-1.23), however
      it was not statistically significant (p>0.05). CONCLUSIONS: Early hysterotomy in
      pregnancy is the main risk factor for scar endometriosis. Increased menstrual
      flow and alcohol consumption are also risk factors, while high parity may be a
      protecting factor.

PMID- 17230294
TI  - Pregnancy outcome and recurrence after conservative laparoscopic surgery for
      borderline ovarian tumors.
AB  - BACKGROUND: The aim of this study was to evaluate the safety and efficacy of
      conservative laparoscopic management of borderline ovarian tumors, and to assess
      pregnancy outcome and recurrence after fertility-sparing surgery. METHODS: From
      1995 to 2005, 43 patients of reproductive age presented with adnexal mass, which
      was subsequently diagnosed as a borderline tumor of the ovary. These patients
      were treated by conservative laparoscopic surgery, with intraoperative staging of
      the disease. Patients were evaluated every 3 months for the first 2 years, and
      then every 6 months thereafter, to determine the best modality for following
      patients after conservative surgery. RESULTS: Three (7%) patients developed a
      recurrence after conservative treatment. Among the 43 patients who had
      conservative surgery, 21 (49%) became pregnant during the follow-up period; 12
      (57%) conceived spontaneously, and the remaining 9 (43%) patients underwent
      caesarean section. CONCLUSIONS: In our opinion, conservative laparoscopic
      treatment of borderline ovarian tumors is an appropriate and reasonable
      therapeutic option for young women with low-stage disease who wish to preserve
      their childbearing potential, because the fertility results are encouraging.
      Recurrence can be noted after this type of treatment, but the cases of recurrent
      disease can be detected with close follow-up and treated accordingly. Careful
      selection of candidates for this kind of treatment is, of course, necessary, and
      close follow-up is required.

PMID- 17230295
TI  - Characterization of surgically transposed ovaries in integrated PET/CT scan in
      patients with cervical cancer.
AB  - BACKGROUND: The purpose of this study was to determine the ovarian findings on
      integrated positron emission tomography/computed tomography scans during follow
      up in cervical cancer patients with ovarian transposition. METHOD: We
      retrospectively reviewed the clinical data and integrated 18F-fluorodeoxyglucose
      positron emission tomography/computed tomography of women with ovarian
      transposition during radical hysterectomy for cervical cancer between December
      2003 and March 2006. RESULTS: Eighty-four premenopausal women had ovarian
      transposition performed during the study period. Twelve positron emission
      tomography/computed tomography scans from 11 patients were registered for the
      current study and three women were diagnosed with metastasis: two in lung and one
      in pelvis. Two patients complained of menopausal symptoms during follow-up, and
      the hormonal tests were consistent with it. In the current study, an integrated
      positron emission tomography/computed tomography scan detected one patient with
      right lower abdominal mass with increased 18F-fluorodeoxyglucose uptake, which
      was identified as a transposed right ovary. Clinical information of ovarian
      transposition was helpful in interpretation of the lesion. In the patient,
      transposed ovary was associated with increased fluorodeoxyglucose uptake, with
      standard uptake values ranging from 3.7 to 5.5. Other positron emission
      tomography/computed tomography scans did not show abnormal uptake of 18F
      fluorodeoxyglucose. CONCLUSIONS: Transposed ovary in premenopausal women may
      appear on integrated positron emission tomography/computed tomography scan as a
      mass with increased 18F-fluorodeoxyglucose uptake, which may be associated with
      preserved ovarian function. Clinical information regarding transposition should
      be noted in order not to interpret these as recurrent or metastatic lesions.

PMID- 17230296
TI  - Prognostic markers of high-grade squamous intraepithelial lesions: the role of
      p16INK4a and high-risk human papillomavirus.
AB  - BACKGROUND: p16INK4a seems to be an indicator of the grade of Human
      Papillomavirus-induced lesions and a possible predictor of the lesion evolution.
      There are few studies about the role of HPV test and p16INK4a in diagnosis of
      high-grade cervical lesions in South-American women. The aim of the present study
      was to evaluate the presence of p16INK4a and high-risk HPV-DNA expression in
      cases diagnosed as squamous intra-epithelial lesion and evaluate their role in
      the approach of high-grade squamous intra-epithelial lesion. METHODS: p16INK4a
      and high-risk Human papillomavirus were investigated in 96 samples of the cervix
      (13 cases of high grade squamous intraepithelial lesions, 26 cases of low grade
      intraepithelial lesions and 57 normal tissues). The p16INK4a was identified by
      immunohistochemistry using the p16INK4a kit (E6H4 clone, DakoCytomation,
      Carpinteria, CA) and Human papillomavirus DNA was classified by hybrid capture
      (Digene). Associations were evaluated by the KAPPA index. RESULTS: The p16INK4a
      was detected in 92.3% of the high-grade squamous intraepithelial lesions, in
      15.4% of the low-grade and in none of the normal tissues. The sensitivity,
      specificity, positive predictive value and negative predictive value for high
      grade lesion were 92.3%, 100%, 100%, and 98.3%, respectively when considering
      p16INK4a expression, and 100%, 70.2%, 43.3% and 100%, respectively when
      considering high-risk HPV. CONCLUSIONS: p16INK4a test was better associated with
      high-grade intraepithelial lesion (kappa = 0.95) than was the presence of high
      risk HPV (kappa = 0.47). Both tests could be complementary to high-grade squamous
      intra-epithelial lesion screening and help to define the diagnosis of the
      inconclusive low-grade/high-grade squamous intraepithelial lesion cases.

PMID- 17230297
TI  - Gadolinium periconceptional exposure: pregnancy and neonatal outcome.
AB  - BACKGROUND: Gadolinium derivatives are ionic paramagnetic contrast agents used to
      enhance magnetic resonance images, labeled as a pregnancy category C by the Food
      and Drug Administration because of a lack of epidemiological studies concerning
      first-trimester exposure. METHODS: Prospective cohort study to determine whether
      gadolinium derivatives exposure in periconceptional period is a risk factor for
      pregnancy or fetal development. RESULTS: We report the outcome of 26 pregnant
      women exposed to gadolinium derivatives in the first trimester without adverse
      effect on pregnancy and neonatal outcome. CONCLUSIONS: Currently, this study
      represents the only prospective investigation of gadolinium derivatives in
      pregnancy, but more data are necessary to exclude a teratogenic risk.

PMID- 17230298
TI  - Leiomyoma of the vagina that caused cyclic urinary retention.

PMID- 17230299
TI  - Hyperreactio luteinalis, presented as an acute abdomen.

PMID- 17230300
TI  - Arias-Stella reaction in an adenomyomatous polyp of the uterus.
AB  - We describe a rare case of an Arias-Stella reaction in an adenomyomatous polyp of
      the endometrium found in the first trimester of pregnancy. A 33-year-old Japanese
      woman, gravida 1, para 1, presented for an initial prenatal examination at 6-week
      gestation; ultrasound revealed a myoma-like solid mass in the cervical canal. An
      abnormal Papanicolaou's smear (highly suspicious of adenocarcinoma) prompted the
      resection of this pedunculated polyp. Histologically, the musculature located in
      the center of the polyp was covered by the endometrium; numerous glands within
      both the endometrium and the musculature exhibited an Arias-Stella reaction. This
      explains the result of Papanicolaou's smear, because subsequent smears - both
      intrapartum and postpartum - were negative. To our knowledge, this is the first
      reported incident of an Arias-Stella reaction in an adenomyomatous polyp. This
      could be one of the diagnostic pitfalls in Papanicolaou's smears taken during
      pregnancy.

PMID- 17230301
TI  - Ectopic pregnancy with negative serum human chorionic gonadotropin.

PMID- 17230302
TI  - Prevalence of depression in women with endometriosis.

PMID- 17230306
TI  - [The psychiatrist and the psychiatric hospital--an analysis of referral and
      aftercare].
AB  - OBJECTIVE: Against the background of the problematic interface between outpatient
      and inpatient care in the German psychiatric health care system, the role of
      psychiatrists in private practice concerning the pathways of psychiatric
      inpatients before and after their hospital stay should be evaluated. METHODS:
      Based on data of the psychiatric basic documentation (DGPPN-BADO) of 4905
      patients admitted to the psychiatric hospital in 2003, predictors of the type of
      referral as well as the outpatient aftercare were analysed by means of logistic
      regression analyses. RESULTS: 9.8 % of patients were referred by psychiatrists in
      private practice. Patients sent by psychiatrists more seldom had an addiction
      disorder, more often were residents of sheltered homes, showed a present episode
      lasting more than three months and had a psychopharmacological pre-treatment with
      an atypical antipsychotic or SSRI. At discharge, outpatient aftercare by
      psychiatrists in private practice was recommended to 32.1 % of inpatients.
      Referral by a psychiatrist in private practice as well as the diagnosis of
      schizophrenia or affective disorder led more often to an outpatient aftercare by
      a psychiatrist. CONCLUSIONS: Due to the small number of patients referred by
      psychiatrists, the cooperation between psychiatric hospital and psychiatrists in
      private practice has to be focused by the quality management of the hospital.

PMID- 17230307
TI  - [Cubital tunnel syndrome--simple nerve decompression or decompression with
      subcutaneous anterior transposition?].
AB  - The purpose of this prospective, randomised and controlled study was to evaluate
      which kind of operative technique for treatment of cubital tunnel syndrome is
      favourable: subcutaneous anterior transposition or nerve decompression without
      transposition. This study included 66 patients suffering from pain and/either
      neurological deficits with clinically and electrographically proven cubital
      tunnel syndrome. 32 patients underwent nerve decompression without transposition,
      whereas 34 underwent subcutaneous transposition of the nerve. Follow-up
      examinations evaluating pain, motor and sensory deficits as well as motor nerve
      conduction velocities were performed three, nine and 24 months postoperatively.
      Irrespectively of operative procedures (simple decompression vs. subcutaneous
      anterior transposition) there were no significant differences between the
      outcomes of the two groups at either postoperative follow-up examination (p >
      0.05).

PMID- 17230308
TI  - [Efficacy and tolerability of quetiapine in hospitalised schizophrenic patients
      during the acute treatment phase: a PMS study].
AB  - We performed a post marketing surveillance study (PMS study) to reveal the
      efficacy and tolerability of orally administered quetiapine in the treatment of
      acute psychosis over a period of up to three weeks. 398 respective inpatients
      were assessed in 88 psychiatric departments in Germany by use of the Clinical
      Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS) as
      well as the clinical impression of psychiatric raters. Safety and tolerability
      were assessed by vital parameters such as blood pressure, hearth rate and weight
      as well as the clinical impression of the psychiatric raters. In addition,
      dosing, concomitant and/or previous pharmacotherapies as well as certain aspects
      of psychiatric and medical history were documented. A significant reduction of
      psychopathology was found during three weeks of drug treatment. Daily dosages of
      quetiapine between 400 and 1200 mg were well tolerated with a limited number of
      adverse and no serious adverse events. Noteworthy, more than 35 % of all patients
      received and tolerated excellently more than 800 mg of quetiapine per day under
      naturalistic treatment conditions, well above the approved maximum daily dosage.
      This study reflects the clinical efficacy and good tolerability of quetiapine
      under real world treatment conditions and is in line with the results of the
      controlled clinical trials of phase II and III.

PMID- 17230310
TI  - [Addiction as loss of self-control? Current concepts on the development and
      treatment of addictive behaviors].

PMID- 17230311
TI  - [Alcohol-related disorders: etiopathology and therapeutic considerations].
AB  - The scientific understanding of the neurobiological priniciples of alcoholism has
      made significant progress in recent years. Especially the effects of ethanol on
      the neurotransmitter-systems are well studied. Dopaminergic and GABAergic
      facilitation contribute to the stimulating effects of low doses of alcohol while
      many of its adverse effects are mediated by glutamatergic inhibition at higher
      doses. A reduced serotonine-metabolism was shown to be a risk factor for the
      development of an alcohol dependence. The historic success of absinthe is
      discussed in this context. Absinthe is a mixture of ethanol and thujone, a
      substance that leads to a GABAergic inhibition as well as a reduced serotonergic
      responsiveness. Many studies substantiate the role of cannabinoid as well as
      striatal opiate-receptors in alcohol-related disorders. Neuroimaging studies
      could prove the important role of the reward system in this connection. Genetic
      factors were shown to be predisposing, however biological and environmental
      factors have a regulatory effect on the gene expression. Disturbances of the hpa
      axis (hypothalamus-pituitary gland-adrenal cortex) were also shown to play a role
      in alcohol dependence. The understanding of these neurobiological principles of
      alcohol-related disorders should contribute to enhance and improve their
      therapeutic options.

PMID- 17230312
TI  - [Diagnostics and treatment of alcohol-related disorders: results of a
      representative study in psychiatric and psychotherapeutic practices].
AB  - BACKGROUND: Alcohol use disorders (AUD) are of high prevalence in the community.
      The aim of the present study is to examine the diagnostic and therapeutic
      strategies of psychiatrists and psychotherapists in patients with AUDs. METHODS:
      A standardized questionnaire was sent to all psychiatrists and psychologists in
      the South Badenia region (n = 745). It consisted of general questions and those
      regarding diagnostic and therapeutic procedures in the last patient seen with an
      AUD. A total of 224 questionnaires sent back by 160 psychotherapists [PT] and 64
      psychiatrists [P] could be included in the analysis. RESULTS: The mean stated
      prevalence of AUDs was 5 %. The mean age of the reported patient was 44 +/- 10
      years, 60 % were men. The initial reason for consultation in psychotherapy was in
      61.9 % depression in comparison to 40.7 % psychiatry (p < or = 0,01). The
      majority of patients seen by psychiatrists (44.1 %) were referred by their
      general practitioners. Standardised screening instruments were rarely used. The
      concordance of the diagnostic judgement and formal ICD 10-criteria was 74.5 % [P]
      vs. 45.5 % [PT] (p </= 0,001). 60 % [P] and 24.1 % [PT] were referred to
      addiction counselling services (p < or = 0,001). Patient related factors were
      largely seen as major impediments for adequate diagnosis and treatment.
      DISCUSSION: The study demonstrates significant differences in the patient
      population and the diagnostic and therapeutic strategies in the two groups of
      therapists. Many aspects of the data point towards the need to improve networking
      and to integrate services to be able to provide better care for patients with
      AUDs.

PMID- 17230313
TI  - [Diagnostics and therapy of alcohol addiction].

PMID- 17230314
TI  - Fibula free flap for mandible reconstruction: analysis of 30 consecutive cases
      and quality of life evaluation.
AB  - The objectives of this study were to evaluate the use of fibula free flaps (FFF)
      for mandible reconstruction in patients with oral cavity cancer and to assess the
      quality of life (QOL) of the patients who underwent reconstructive surgery.
      Thirty patients with T(3), T(4) oral cavity carcinoma underwent surgical
      resection of the primary tumor infiltrating the mandible or primarily originating
      from the mandible. According to the length (less or more than 8 cm) and
      localization (anterior or posterior) of the mandibular defect, patients were
      subdivided into four groups. In all cases an osseoseptocutaneous FFF was chosen
      for postresective defect reconstruction. To reconstruct anterior mandibular
      defects, two osteotomies were needed to give the fibula a proper shape. For
      extended defects, the fibula usually required more than one osteotomy. Skin
      islands were designed based on Doppler cutaneous perforator findings. The fibular
      free skin islands remained viable in all patients and no partial or total skin
      loss was observed. In the majority of patients (87 percent) the facial artery was
      used for arterial anastomosis. In 6 month follow-ups, the QOL was evaluated as
      very good except for socioeconomic items. Pain was mild and incidental.
      Appearance and subjective feeling scores were excellent in two groups with
      mandibular defects smaller than 8 cm, although in patients with larger defects,
      they were still very good. Functional effects remained good, and they correlated
      with the size of defects. In contrast, social activities, recreation, and
      employment were below patients' expectations and generally reflected the current
      situation in Poland, but no correlation with the results of reconstruction was
      found. The present results show that osseocutaneous fibula free flap used in
      reconstructive surgery for cancer of the oral cavity allows more radical and
      aggressive resection with very good or excellent functional and aesthetic
      outcome. Estimated QOL seems an important part of evaluation of the treatment
      outcome.

PMID- 17230315
TI  - Free fibula transfer in the treatment of difficult distal tibia fractures.
AB  - Management of the high-grade open distal tibia fracture remains problematic. The
      authors reviewed the charts of 14 cases of distal tibia and tibial plafond
      fractures reconstructed with a free fibula transfer. Six cases involved a plafond
      defect, and the fibula was used to arthrodese the tibio-talar joint. Seven cases
      included a skin paddle. Three of the four patients with osteomyelitis cleared
      their infection. Twelve patients went on to osseous union, and two were
      ultimately treated with amputation. Patients who went on to union had an average
      of 1.1 subsequent procedures, began full weightbearing in an average of 5.8
      months, and were weightbearing without any assistive devices by an average of 8.5
      months. There was no significant correlation between the time to full
      weightbearing and either the presence of infection or the length of the original
      defect. In this series, 86 percent success was obtained when a free fibula
      transfer was used either to bridge a tibial non-union or to promote arthrodesis
      of the tibio-talar joint.

PMID- 17230316
TI  - Posterolateral cervical vein as a recipient vein in reconstructive microvascular
      surgery of the head and neck.
AB  - Free flaps are becoming the preferred method of choice for head and neck
      reconstruction. However, many patients who have undergone radiotherapy and
      radical neck dissection or who require treatment for recurrent tumor, often
      present difficulty in choosing recipient vessels. The authors have noted a
      potential recipient vein coursing vertically along the anterior ridge of the
      trapezius muscle. They used this vein as the recipient vein in two patients; the
      two free flaps were transferred successfully without complications. This vein,
      which they provisionally named the posterolateral cervical vein (PLCV), is
      considered an important option as a recipient vein in head and neck
      reconstruction when more commonly used recipient cervical veins are unavailable.

PMID- 17230317
TI  - Temporomandibular joint reconstruction using a vascularized bone graft with
      Alloderm.
AB  - Vascularized free bone grafts have been used extensively for reconstruction of
      the mandible. When surgical resection includes the temporomandibular joint,
      definitive management remains controversial. We describe a novel technique that
      involves the use of a fibula free flap with Alloderm to reconstruct the lateral
      hemi-mandible and temporomandibular joint capsule. The study was performed by
      retrospective review of a case series at an academic center. Patients undergoing
      composite resection of the lateral hemi-mandible including the condyle with
      disruption of the temporomandibular joint were evaluated. These patients were all
      reconstructed with a vascularized fibula free flap with an Alloderm neocondyle
      reconstruction. There were nine patients with a mean age of 49.9 years. Mean
      follow-up was 13.1 months. There were no flap failures, infections, or
      complications. All patients reported improved facial symmetry, excellent jaw
      opening, and acceptable occlusion. All patients were able to tolerate a soft oral
      diet following surgery. No patients required gastrostomy tubes postoperatively.
      The lateral hemi-mandible and temporomandibular joint can be resected and
      successfully reconstructed using a fibula free flap with Alloderm to create the
      neocondyle. Improved postoperative cosmesis, decreased trismus, adequate jaw
      opening, minimal jaw drift, and the ability to chew were achieved in the majority
      of patients treated in this manner.

PMID- 17230318
TI  - The vessel protector: an instrument for operative microsurgery.
AB  - Since the introduction of microsurgery and free flap transfers, the techniques of
      dissection and harvesting of flaps and their vascular pedicles have continuously
      advanced. As the vascular pedicles of free and pedicled flaps should be protected
      during their harvest or dissection, the usual trials to protect pedicle vessels
      depend ultimately on the surgeon and clinical experience. A new microsurgical
      instrument, the vessel protector, facilitating protection and holding of the
      vascular pedicle has been developed. Through experimental and clinical trials,
      the instrument has been demonstrated to protect the structures inside a distal
      coiled end while also holding them. This has several advantages over conventional
      dissection by jeweler's forceps and scissors.

PMID- 17230319
TI  - Does chemotherapy impair the bone healing and biomechanical stability of
      vascularized rib and fibula grafts?
AB  - The purpose of this study was to observe the impact of chemotherapy on the
      healing and biomechanical properties of vascularized bone grafts. Ten male beagle
      dogs were divided into two experimental groups: a chemotherapy group (CH) and
      control group (C). Group CH received adjuvant and neo-adjuvant chemotherapy. Each
      animal of both groups underwent the following operative procedures. The 5th and
      7th rib were removed and replaced by vascularized pedicle transfers of the
      adjacent 4th and 8th rib. Additionally, a free fibular flap was elevated and
      retransferred to the same anatomic position. The rate of bony union on plain x
      ray was 100 percent in group C, 30 percent in the vascularized rib, and 80
      percent in the fibula grafts of group CH. Microangiography demonstrated no
      avascular bone segments in group C and in the fibula flaps of group CH. The
      vascularized ribs of group CH presented with 20 percent avascular bone segments.
      Biomechanical tests focusing on the durability of the vascularized grafts against
      bending and torsion forces demonstrated a reduction of the average maximum
      bending times by 17 percent and 23.9 percent compared to the controls ( P <
      0.05). The twisting times were reduced by 13.8 percent (n.s.) and 32.5 percent (
      P < 0.05). The data demonstrated a clear worsening in bone healing and stability
      after simulated adjuvant and neo-adjuvant chemotherapy. Thus, a large animal
      model was established for the further determination of the effects of
      chemotherapy on different vascularized bone transfers.

PMID- 17230320
TI  - Protective effects of monoclonal antibody to intercellular adhesion molecule-1 in
      venous ischemia-reperfusion injury: experimental study in rats.
AB  - Flaps with venous occlusion have a decreased survival rate compared with arterial
      occlusion. It seems that several factors are involved in the etiology of total
      venous occlusion, including free radicals, edema, thrombosis, and reperfusion
      injury. In the present study, the authors evaluated the blockage of
      polymorphonuclear leukocyte endothelial adhesion by using a monoclonal antibody
      to the intercellular adhesion molecule 1 (ICAM-1) ligand to prevent venous
      ischemia-reperfusion injury in rat epigastric island flaps. A skin flap (3 x 4
      cm) supplied by the superficial epigastric artery and vein was harvested
      unilaterally in 40 male Wistar rats. Total venous occlusion of the skin flap was
      achieved. Arterial inflow was left intact. Rats were randomly divided into four
      groups (n = 10). In Group 1; rats were intravenously pretreated with 0.5 ml of
      0.9 percent normal saline 15 min before applying a venous clamp, and the flaps
      were subjected to 6 hr of venous ischemia. In Group 2; rats were intravenously
      pretreated with 0.05 mg of monoclonal antibody to the intercellular adhesion
      molecule 1 (0.20 mg/kg) in 0.5 ml of 0.9 percent normal saline 15 min before
      applying the venous clamp, and the flaps were subjected to venous ischemia as in
      Group 1. In Group 3; rats were pretreated as in Group 1, and the flaps were
      subjected to 8 hr of venous ischemia. In Group 4; rats were pretreated as in
      Group 2, and the flaps were subjected to 8 hr of venous ischemia. The flaps were
      assessed histologically and by measuring viable and non-viable areas on
      postoperative day 7. Flap measurements revealed that blocking the action of ICAM
      1 IN VIVO by administering monoclonal antibody significantly attenuated ischemic
      injury after 6 or 8 hr of venous occlusion.

PMID- 17230321
TI  - Comparison of experimental microvascular end-to-end anastomosis via VCS-Clips
      versus conventional suture technique in an animal model.
AB  - In this experimental study on 96 CD rats, microvascular end-to-end anastomoses
      created via suture or alternatively by means of a VCS-Clip-Application-System,
      were compared. The aorta abdominalis of the animals, with a diameter of 1.5 +/-
      0.2 mm, was experimentally dissected, and the free ends of the vessel then
      anastomosed. The results were evaluated using sonography, microangiography,
      histologic examination, and vascular imprints. Postoperative examination was
      carried out after 1, 3, 7, 14, or 30 days. Major advantages of the VCS-Clip
      technique over suturing were that it was easy to learn, significantly faster to
      perform (execution of anastomosis 10.9 +/- 2.6 min versus 19.4 +/- 5.0 min), and
      produced significantly more favorable histologic results in terms of less
      inflammatory response, foreign body reaction, necrosis of the tunica media,
      hyperplasia of the intima, and thrombosis of the vessel lumen. The main
      disadvantage of the clip technique was a significantly higher rate of stenoses
      (15.8 +/- 6.0 versus 4.1 +/- 6.6 percent).

PMID- 17230322
TI  - Vastus lateralis free flap for soft tissue coverage of a lower extremity diabetic
      ulcer.

PMID- 17230323
TI  - Dermal microcirculation of the free TRAM flap following adverse drug reaction.

PMID- 17230324
TI  - Microdialysis to monitor scalp flap viability.

PMID- 17230325
TI  - [Influence of thyroid cartilage ossification in laryngeal ultrasound].
AB  - BACKGROUND: Topological features of the larynx and hypopharynx may be depicted
      during sonographic examination of the neck, although ultrasound is seen of minor
      diagnostic importance. The varying extend of thyroid cartilage ossification
      appears to be the major limiting factor. We intended to assess the sonographic
      accessability of laryngeal structures with high end resolution ultrasound
      devices. METHODS AND PATIENTS: We examined 101 patients endoscopically and by
      ultrasound. Normal laryngeal findings and pathologies were examined and analysed
      considering limitations by thyroid cartilage ossification. RESULTS: Despite
      varying grades of ossification, the majority of laryngeal structures were clearly
      displayed by ultrasound. Ossification was increasing in the elderly. In 16 cases
      (16 %) ossification prevented a successful evaluation. In 9 cases of malignant
      tumor and one laryngocele sonographic assessment was able to contribute
      additional diagnostic information. CONCLUSIONS: Ultrasound of the larynx requires
      methodical experience of the operator but is capable to depict relevant anatomic
      structures, even with presence of thyroid cartilage ossification, thus being able
      to increase diagnostic impact and may save additional imaging modalities.

PMID- 17230326
TI  - [Occupational cancer--burdens of the past or actual threat?].

PMID- 17230327
TI  - [What the Institute for Quality and Cost-Effectiveness in the Health System could
      and should do better].

PMID- 17230328
TI  - [Polypharmacy, compliance and non-prescription medication in patients with
      cardiovascular disease in Germany].
AB  - BACKGROUND AND OBJECTIVE: The expenses of health insurances are continuously
      raising. With implementation of evidence-based medicine resulting in
      polypharmacy, compliance is decreasing and patients as well as physicians are
      facing unintentional drug interactions. Furthermore the arbitrary use of
      additional drugs apart from prescribed medication has to be considered. The
      objective of this study was to analyse polypharmacy, compliance and utilisation
      patterns for non-prescription medications (OTC) in patients with cardiovascular
      diseases. METHODS: 100 patients with cardiovascular diseases (45 women, 55 men,
      58 - 87 years) were interviewed using a questionnaire. The compliance was
      determined by the Morisky-Score. RESULTS: 78 % of the patients received more than
      four pills every day (median 8.34). Most common products were beta-blockers (89
      %), ACE-Inhibitors/Sartans (69 %) and aspirin (65 %). Only 52 % of the patients
      knew the indications of their medication. Although 83 % of the patients claimed
      to be absolutely compliant concerning their medication, the Morisky-Score
      revealed a high compliance only in 52 %. The compliance decreased significantly
      if the number of prescribed medication increased to more than four pills a day.
      48 % of the patients took regularly non-prescription products, 35 % more than
      three additional products daily. Most commonly multivitamins, minerals, herbals
      and non-steroidal anti-inflammatory drugs were used. This non-prescription
      medication did not affect the compliance of the patients. CONCLUSIONS:
      Polypharmacy with more than four pills daily leads to a lower compliance and can
      therefore influence the implementation of guideline-medicine. Non-prescription
      medication is widely used and should be considered because of their potential
      side-effects and drug interactions.

PMID- 17230329
TI  - [Acute cardiogenic shock with inferior myocardial infarction associated with an
      abnormal origin of the coronary arteries].
AB  - HISTORY: A 45-year-old previously healthy man was admitted as an emergency having
      suddenly gone into cardiogenic shock. He had not been on any medications. The
      only known risk factor for cardiovascular disease was heavy smoking.
      INVESTIGATION AND DIAGNOSIS: The patient was awake and responsive on admission
      but showed early signs of cardiogenic shock with hypotension (systolic blood
      pressure 70 mmHg) and a peripheral pulse rate of 25 beats/min, cold sweat,
      peripheral cyanosis, nausea and retching. A 12-lead electrocardiogram revealed a
      bradycardic idioventricular rhythm with a wide QRS and monophasic ST segment
      elevation in the inferior and posterolateral leads. TREATMENT AND COURSE: The
      patient required resuscitation immediately after admission because of ventricular
      fibrillation and was intubated. Cardiopulmonary measures of resuscitation had to
      be continued while an emergency coronary angiography was performed. This
      demonstrated an anomalous origin of both coronary arteries from the right sinus
      of Valsalva and proximal occlusion of a dominant right coronary artery (RCA).
      Several episodes of ventricular fibrillation required repeated DC cardioversion
      until a regular rhythm was maintained. Closed-chest cardiac compression had to be
      continued until percutaneous coronary angioplasty had re-established flow in the
      artery and a long stent had been inserted, with subsequent hemodynamic
      stabilization and restitution of a normal cardiac rhythm. The patient was
      extubated 3 days after admission. CONCLUSION: Sudden onset of cardiogenic shock
      and extensive monophasic ST elevations in the ECG without clear-cut localization
      of coronary supply to the infarcted area should bring to mind an atypical
      coronary supply pattern or possible coronary artery anomaly.

PMID- 17230330
TI  - [Older (not recent) covered perforation of the caecum due to ischaemic colitis].

PMID- 17230331
TI  - [Potential and limitations of serological Epstein-Barr virus diagnostics].

PMID- 17230332
TI  - [Sport and the digestive system].

PMID- 17230333
TI  - [Hormonal treatment of cancer of the prostate: review and present status].

PMID- 17230335
TI  - List of referees 1992.

PMID- 17230334
TI  - [The chief physician as the executive].

PMID- 17230336
TI  - Effects of Near-Ultraviolet Light on Alkaloid Production in Catharanthus roseus
      Plants.
AB  - Artificial near-ultraviolet light with a peak at 370 nm and the light of natural
      radiation with wavelengths between 290 and 380 nm stimulated the synthesis of
      dimeric indole alkaloids in intact plants of CATHARANTHUS ROSEUS. The artificial
      light also specifically stimulated an IN VITRO FMN-mediated, non-enzymatic
      coupling of vindoline and catharanthine to synthesize an iminium intermediate,
      the IN VIVO precursor of dimeric alkaloid synthesis. These results suggest that
      near-ultraviolet light is necessary for catharanthine oxidation as a trigger
      reaction of dimer synthesis in the plants.

PMID- 17230337
TI  - Helenalin Acetate in in vitro Propagated Plants of Arnica montana.
AB  - Propagated "IN VITRO" shoots and plantlets of ARNICA MONTANA L. (Asteraceae) have
      been shown to produce sesquiterpene lactones, i.e. helenalin and 11,13
      dihydrohelenalin esters. The compounds were detected in green organs only; roots
      of the plantlets contained no sesquiterpene lactones. The helenalin acetate
      content in leaves of the plantlets (0.073% dry wt) was 4-times higher than in
      proliferated shoots (0.016% dry wt). The best rate of shoot multiplication was
      achieved on MS medium, supplemented with NAA 0.5mg/l and Kn 2.5 mg/l (formation
      of 22 shoots within 8 weeks).

PMID- 17230338
TI  - Hydroxycinnamic Acid Derivatives, Caffeoylmalic and New Caffeoylaldonic Acid
      Esters, from Chelidonium majus*,1.
AB  - HPLC analysis of a hydrolyzed extract obtained from the aerial parts of
      CHELIDONIUM MAJUS yielded 0.4% caffeic, 0.06% P-coumaric, and 0.02% ferulic
      acids; gentisic and P-hydroxybenzoic acids were below 0.01%. The caffeic acid
      derivatives occur as esters of which four were isolated using gel permeation
      chromatography, centrifugal partition chromatography and HPLC; they were assigned
      on the basis of their spectroscopic data ( (1)H-, (13)C-NMR, UV, MS) as the new (
      )-2-( E)-caffeoyl- D-glyceric acid, (-)-4-( E)-caffeoyl- L-threonic acid, (-)-2-(
      E)-caffeoyl- L-threonic acid lactone, and the known (+)-( E)-caffeoyl- L-malic
      acid.

PMID- 17230339
TI  - Polyphenols from Rhodiola crenulata.
AB  - A novel gallotannin, crenulatin ( 7), has been isolated from RHODIOLA CRENULATA.
      The structure was elucidated by spectral analyses (including 2D-NMR spectral
      measurements) and chemical methods. Also six known polyphenols have been isolated
      and identified.

PMID- 17230340
TI  - Diterpenoid Alkaloids from Delphinium caeruleum.
AB  - A new minor diterpenoid alkaloid, caeruline, was isolated from DELPHINIUM
      CAERULEUM Jacq. ex Camb. Its structure was elucidated as 1 on the basis of
      spectral evidence. Along with this new compound, three known diterpenoid
      alkaloids were also isolated from this plant and identified as tatsiensine,
      delcosine, and lycoctonine which had not been found in this herb previously.

PMID- 17230341
TI  - The Filament Bundle of Mentha piperita.
AB  - Bundles consisting of 6 to 8 parallel filaments (6 nm thick) are localized in
      both the cytoplasm and the nucleus - particularly in mesophyll cells and in 3
      celled capitate glandular hairs, but not in the 10-celled glandular peltate hairs
      of the leaves of MENTHA PIPERITA. They are present in as yet 8 investigated
      species of the genus MENTHA, but not in 8 further genera of the Lamiaceae. The
      bundles are therefore genus-specific; they consist of protein only. A possible
      connection with the production of essential oil is discussed.

PMID- 17230342
TI  - Pyrrolizidine alkaloids of the genus homogyne.

PMID- 17230343
TI  - Microminutinin: A Novel Coumarin from Micromelum minutum.

PMID- 17230344
TI  - Analysis of the Essential Oil from Helichrysum picardii.

PMID- 17230345
TI  - Effect of Calcium, Strontium, and Magnesium Ions on the Formation of
      Phytosteroids in Callus Cultures of Agave amaniensis.

PMID- 17230346
TI  - Thymoquinone from Eupatorium ayapana.

PMID- 17230347
TI  - Erratum.

PMID- 17230348
TI  - Alkaloids of Siparuna Griseo-flavescens.

PMID- 17230349
TI  - Analysis of Alkaloids from Physalis peruviana by Capillary GC, Capillary GC-MS,
      and GC-FTIR.
AB  - The alkaloid composition of the aerial parts and roots of PHYSALIS PERUVIANA was
      analysed by capillary GC (GC (2)), GC (2)-MS and GC (2)-FTIR. Eight alkaloids
      were identified, three of those alkaloids are 3beta-acetoxytropane and two N
      methylpyrrolidinylhygrine isomers, which were not previously found in the genus
      PHYSALIS. A reproduction of the identification of alkaloids detected in the plant
      by the use of retention indices has been proposed.

PMID- 17230350
TI  - Geraniol dehydrogenase: a determinant of essential oil quality in lemongrass1.
AB  - Geraniol dehydrogenase, the specific enzyme involved in geraniol to citral TRANS
      (geranial) transformation, activity was monitored in various lemongrass cultivars
      differing in amounts and relative percentages of citral and geraniol in their
      essential oils. The enzyme activity had a positive and significant association
      with citral to geraniol, and geranial to geraniol ratios. The results are
      suggestive of a strong relationship between the enzyme activity and essential oil
      quality in lemongrass cultivars.

PMID- 17230351
TI  - New Monoterpenes from Cunila spicata.
AB  - The leaves of CUNILA SPICATA Benth. (Lamiaceae) yielded a monoterpene diacetate
      called iso-rosiridol diacetate ( 1) and two isomeric hydroperoxymonoterpenes ( 2,
      3) as well as beta-sitosterol, phytol, cadinol, linalool, dihydrocarveol, geranyl
      and neryl acetate. Structure elucidation was done by high-field NMR-techniques.

PMID- 17230352
TI  - Four New Hydroazulenoid Diterpenes from the Tropical Marine Brown Alga Dictyota
      volubilis.
AB  - The marine brown alga, DICTYOTA VOLUBILIS, was found to contain four unusually
      substituted hydroazulenoid diterpenes ( 1 - 4) as well as the known compounds
      dictyol G acetate ( 5) and dilophol. The structures of all isolates were secured
      by detailed analysis of their spectroscopic data; IR, MS, and NMR.

PMID- 17230353
TI  - A Novel Morphinandienone Alkaloid from Fissistigma oldhamii.

PMID- 17230354
TI  - Chemical Composition of The Essential Oil and Aqueous Extract of Plectranthus
      amboinicus.

PMID- 17230355
TI  - Essential Oil of Eupatorium odoratum.

PMID- 17230356
TI  - Volatile Constituents of Xylopia nitida Leaf Oil1.

PMID- 17230357
TI  - Elicitor-Induced Formation of Coumarin Derivatives in Suspension Cultures of
      Pimpinella anisum.

PMID- 17230358
TI  - High Content of Hydroxycinnamic Acids Esterified with (+)-D-Malic Acid in the
      Upper Parts of Fumaria officinalis1.

PMID- 17230359
TI  - Alkaloids of Guatteria diospyroides.

PMID- 17230360
TI  - Pyrrolizidine Alkaloids from Arnebia euchroma*.

PMID- 17230362
TI  - Review of "principles of pharmacology. A tropical approach".

PMID- 17230361
TI  - Review of "ethonopharmacologie: sources methodes, objectifs/ethnopharmacology:
      sources, methods, objectives".

PMID- 17230363
TI  - Protein kinase inhibitors in plants of the myrtaceae, proteaceae, and
      leguminosae.
AB  - Methanolic extracts of leaves, flowers, stems, bark, and other parts of
      representative plants of the Myrtaceae, specifically of the EUCALYPTUS,
      MELALEUCA, THRYPTOMENA, CALLISTOMEN, ACMENA, AND ANGOPHORA genera, variously
      contain high levels of inhibitors of plant Ca (2+)-dependent protein kinase
      (CDPK) and of Ca (2+)-calmodulin-dependent myosin light chain kinase (MLCK). In
      terms of the protein kinase inhibition unit (PKIU), defined as the amount in the
      standard protein kinase assays causing 50% inhibition of protein kinase activity,
      these inhibitor levels ranged from the non-detectable to 179,000 PKIU (gram fresh
      weight) (-1) [(g FW) (-1)] and there was no consistent pattern of inhibitor
      distribution. A variety of other plants tested had low or non-detectable levels
      of CDPK and MLCK inhibitors. Plants of the EUCALYPTUS, MELALEUCA, ANGOPHORA, and
      GREVILLEA genera contained inhibitors of the catalytic subunit of the cyclic AMP
      dependent protein kinase (cAK), inhibitor levels ranging from 20,000 to 9,600,000
      PKIU (g FW) (-1). In general, cAK inhibitor levels found in the Myrtaceae were
      mostly much higher than levels of CDPK and MLCK inhibitors and reversed phase
      HPLC of such plant extracts revealed a multiplicity of components associated with
      cAK inhibitory activity. These IN VITRO screening procedures enable rapid
      detection and quantitation of levels of bioactive plant defence compounds with
      medicinal potential.

PMID- 17230364
TI  - Production of Flavonoids in Cell Cultures of Crataegus monogyna.
AB  - Callus and suspension cultures were established from shoot tips of CRATAEGUS
      MONOGYNA L. in Murashige and Skoog (MS) medium and a modified MS medium. The
      flavonoid glycosides vitexin, vitexin 2- O-rhamnoside, rutin, and hyperoside, as
      well as the aglycones apigenin, luteolin, and quercetin, could be detected by TLC
      and HPLC in, however, varying amounts. Additionally, the contents of procyanidins
      were determined. The ratio between the contents of flavonoids and procyanidins is
      discussed.

PMID- 17230365
TI  - Study of the Essential Oil from Juniperus communis "Berries" (Cones) Growing Wild
      in Greece.
AB  - Capillary GC and GC-MS analysis of the essential oil from the cones of JUNIPERUS
      COMMUNIS L. grown wild in Greece showed a high content of alpha-pinene (ca 27%),
      sabinene (13%), germacrene-D (10%), and myrcene (9%). The total oil (yield 2.95%)
      consisted of almost 105 constituents, 77 of which representing 93.1% were
      identified. As the main component of the oxygenated monoterpenes was found the
      terpinen-4-ol (1.37%). Seasonal investigation of the essential oils showed mainly
      quantitative variations among the constituents.

PMID- 17230366
TI  - A comparative study on commercial samples of phellodendri cortex.
AB  - A total of 31 commercial samples of Phellodendri cortex (Rutaceous plant) which
      originated from PHELLODENDRON AMURENSE Ruprecht, P. CHINENSE Schneid, P. WILSONII
      Hayata et Kanehira, and P. AMURENSE Rupr. var. SACHALINENSE Fr. Schm.,
      respectively, were collected from the Taiwan and Japan herbal markets. The
      contents of five quaternary alkaloids (berberine, palmatine, jatrorrhizine,
      phellodendrine and magnoflorine) in these samples were determined by capillary
      electrophoresis. It was found that P. WILSONII (4.10 +/- 0.78%) and P. AMURENSE
      var. SACHALINENSE (4.18 +/- 1.03%) were superior to P. AMURENSE (1.55 +/- 0.72%)
      and P. CHINENSE (1.54 +/- 0.60%). Berberine was the major alkaloid in almost all
      samples. In comprised about 80% of the total alkaloids in the first two of the
      four herbs named above, but only about 40% in the latter two. From the data on
      the chemical analysis of the herb's constituents, as well as the herb's texture
      and color, we can postulate the origin and quality of a herb drug.

PMID- 17230367
TI  - An Improved Method for the Isolation of Qinghao (Artemisinic) Acid from Artemisia
      annua.

PMID- 17230368
TI  - Flavonoids from the Aboveground Parts of Lycopus virginicus.

PMID- 17230369
TI  - Melosatin D: A New Isatin Alkaloid from Melochia tomentosa Roots.

PMID- 17230370
TI  - Two New Sterols from the Marine Red Alga Gracilaria edulis1.

PMID- 17230371
TI  - Metabolism of jasmonic Acid in suspension cultures of eschscholtzia.

PMID- 17230372
TI  - Squamocin and Rolliniastatin I from the Seeds of Annona reticulata.

PMID- 17230373
TI  - Diosbulbin-B from the Leaves and Stems of Dioscorea bulbifera: 1H-1H and 13C-1H
      COSY NMR Studies.

PMID- 17230374
TI  - Flavonoid Glycosides from Lysimachiae Herba and Lysimachia christianae var.
      typica1.

PMID- 17230375
TI  - [Ebola and Marburg fever--outbreaks of viral haemorrhagic fever].
AB  - With an increasing frequency of traveling and tourism to exotic countries, a new
      threat-import of rare, very dangerous infections-emerges in humane medicine.
      Ebola fever and Marburg fever, whose agents come from the same group of
      Filoviridae family, belong among these diseases. The natural reservoir of these
      viruses has not yet been precisely determined. The pathogenesis of the diseases
      is not absolutely clear, there is neither a possibility of vaccination, nor an
      effective treatment. Fever and haemorrhagic diathesis belong to the basic
      symptoms of the diseases. Most of the infected persons die, the death rate is 70
      88 %. The history of Ebola fever is relatively short-30 years, Marburg fever is
      known almost 40 years. Hundreds of people have died of these diseases so far. The
      study involves epidemics recorded in the world and their epidemiological
      relations. Not a single case has been recorded in the Czech Republic,
      nevertheless a sick traveler or infected animals are the highest risk of import
      these diseases. In our conditions, the medical staff belong to a highly
      endangered group of people because of stringent isolation of patients, strict
      rules of barrier treatment regime and high infectivity of the diseases. For this
      reason, the public should be prepared for possible contact with these highly
      virulent infections.

PMID- 17230376
TI  - [Travel during pregnancy and possibilities of vaccination].
AB  - Pregnancy presents special medical problem where we need to take into account
      travel risks regarding pregnant women and the health limits as a consequence of
      pregnancy. It is also important to consider the fact that active prevention and
      treatment approaches are to a large degree limited by the pregnancy. The most
      optimal period for travelling is the second trimester. In most cases, the
      potential risk of administering the vaccine is theoretical and not based on
      clinical evidence. Pregnancy presents a special problem regarding many aspects of
      immunization: benefit of vaccination, potential disease risk to the mother and
      fetus and safety of vaccine to mother and fetus itself. In general, pregnant
      patients should avoid live vaccines. Vaccination with inactivated, conjugated,
      polysacahecride vaccines and toxoids is possible. The first trimester of
      pregnancy is the most vulnerable period because of theoretical risk of harmful
      effects to the fetus.

PMID- 17230377
TI  - ["Economy class syndrome"--common risk of travelers?].
AB  - Economy class syndrome is the term for cases of venous thrombosis/, that start in
      connection with travelling for long distance. Syndrome occurs most frequently in
      economy class of flying. Because of crowded uncomfortable conditions by sitting,
      without movement during longer journey by plane can cause thrombosis, especially
      for patients with risk factors. Sequentially thrombembolism can occur. The most
      often risk factors are age, obesity, hormonal contraception, previous thrombosis
      in case history, smoking, immobilization, diabetes mellitus, diseases of vascular
      system and kidneys, and others.

PMID- 17230378
TI  - [Quantitative microbiological diagnostic method of intravascular catheters
      infection using the BacT/Alert SA bottles].
AB  - OBJECTIVE: The study describes a method of quantitatively examining vascular
      catheters with the aid of hemocultural devices BacT/Alert. MATERIAL AND METHODS:
      The amount of bacteria present on the surface of the vascular catheters was
      determined based on the time to detection (TTD) in hemocultural vials inoculated
      with bacterial suspension stirred off the catheter surface. RESULTS: A total
      number of 348 vascular catheters was examined with this new method. Positive
      cultures were detected in 26 (7.5 %) catheters. Accordance to the results of
      microbiological catheter examination with clinical condition of the patient was
      found in 93.1 %. False positivity occurred in 1.1 % (4) and false negativity in
      5.7 % (20) of cases. On the basis of clinical symptoms 42 cases of catheter
      sepsis were diagnosed out of which 22 (52.4 %) positive microbiological
      quantitative examinations of vascular catheters were established. The most
      frequent pathogen was coagulase negative staphylococci. CONCLUSIONS: The new
      method, when compared with present methods, is simpler, faster and able to detect
      the most frequent agent of catheter infection.

PMID- 17230379
TI  - [The first case of imported infection of Chikungunya virus in the Czech
      Republic].
AB  - The authors describe the first confirmed case of tropical fever caused by
      Chikungunya virus imported into the Czech Republic. As the virus belonging to the
      Alphavirus genus of the Togaviridae family is transmitted by mosquitoes of the
      genus Aedes it is classified as an arbovirus. A 43-year-old woman became ill
      following her arrival from the island of Mauritius where she had stayed during an
      epidemic. The patient presenting with typical symptoms of the disease recovered
      completely. Chikungunya virus as the etiological agent was confirmed
      serologically by the complement fixation reaction in the Czech National Reference
      Laboratory for Arboviruses.

PMID- 17230380
TI  - [Murine typhus - rare cause of fever return from Egypt].
AB  - Authors present a case report of 42-year male who spent 14 days in August of 2003
      in Egyptian seaside summer town Hurghada and later he was admitted to the
      Infectious Disease Department Prague with the fever lasting 4 days. His symptoms
      were as follows: strong headache and dry cough. On the 7th and 8th day appeared
      transient maculopapular rash, laboratory test revealed a slightly elevated C
      reactive protein and elevation of amino transferases up to 5 times higher than
      range values, chest X-ray showed hypoventilation opacities on the lower lung
      fields, other findings were non-specifically changed or normal. The fever dropped
      after 15 days without any response to administered antibiotics
      amoxicillin/clavulanate, clarithromycin a ofloxacin. Weil-Felix reaction with
      antigen Proteus OX19 (1 : 5120) was highly positive and positive antibodies IgG
      and IgM against Rickettsia typhi were positive. Later doxycycline was given,
      problems fully subsided, laboratory values were normalised up to six weeks from
      the beginning of the disease. Diagnosis was completed as murine typhus. The
      patient excluded arthropode bit. The authors considered the possibility of
      inhaled contaminated dust during his visit of the port. The above given case was
      firstly referred in the Czech Republic and still it is the only case.

PMID- 17230381
TI  - Duration of time on shift before accidental blood or body fluid exposure for
      housestaff, nurses, and technicians.
AB  - BACKGROUND: Shift work has been found to be associated with an increased rate of
      errors and accidents among healthcare workers (HCWs), but the effect of shift
      work on accidental blood and body fluid exposure sustained by HCWs has not been
      well characterized. OBJECTIVES: To determine the duration of time on shift before
      accidental blood and body fluid exposure in housestaff, nurses, and technicians
      and the proportion of housestaff who sustain a blood and body fluid exposure
      after 12 hours on duty. METHODS: This retrospective, descriptive study was
      conducted during a 24-month period at a large urban teaching hospital.
      Participants were HCWs who sustained an accidental blood and body fluid exposure.
      RESULTS: Housestaff were on duty significantly longer than both nursing staff
      (P=.02) and technicians (P<.0001) before accidental blood and body fluid
      exposure. Half of the blood and body fluid exposures sustained by housestaff
      occurred after being on duty 8 hours or more, and 24% were sustained after being
      on duty 12 hours or more. Of all HCWs, 3% reported an accidental blood and body
      fluid exposure, with specific rates of 7.9% among nurses, 9.4% among housestaff,
      and 3% among phlebotomists. CONCLUSIONS: Housestaff were significantly more
      likely to have longer duration of time on shift before blood and body fluid
      exposure than were the other groups. Almost one-quarter of accidental blood and
      body fluid exposures to housestaff were incurred after they had been on duty for
      12 hours or more. Housestaff sustained a higher rate of accidental blood and body
      fluid exposures than did nursing staff and technicians.

PMID- 17230382
TI  - Fatigue increases the risk of injury from sharp devices in medical trainees:
      results from a case-crossover study.
AB  - BACKGROUND: Extreme fatigue in medical trainees likely compromises patient
      safety, but regulations that limit trainee work hours have been controversial. It
      is not known whether extreme fatigue compromises trainee safety in the healthcare
      workplace, but evidence of such a relationship would inform the current debate on
      trainee work practices. Our objective was to evaluate the relationship between
      fatigue and workplace injury risk among medical trainees and nontrainee
      healthcare workers. DESIGN: Case-crossover study. SETTING: Five academic medical
      centers in the United States and Canada. PARTICIPANTS: Healthcare workers
      reporting to employee healthcare clinics for evaluation of needlestick injuries
      and other injuries related to sharp instruments and devices (sharps injuries).
      Consenting workers completed a structured interview about work patterns, time at
      risk of injury, and frequency of fatigue. RESULTS: Of 350 interviewed subjects,
      109 (31%) were medical trainees. Trainees worked more hours per week (P<.001) and
      slept less the night before an injury (P<.001) than did other healthcare workers.
      Fatigue increased injury risk in the study population as a whole (incidence rate
      ratio [IRR], 1.40 [95% confidence interval {CI}, 1.03-1.90]), but this effect was
      limited to medical trainees (IRR, 2.94 [95% CI, 1.71-5.07]) and was absent for
      other healthcare workers (IRR, 0.97 [95% CI, 0.66-1.42]) (P=.001).Conclusions.
      Long work hours and sleep deprivation among medical trainees result in fatigue,
      which is associated with a 3-fold increase in the risk of sharps injury. Efforts
      to reduce trainee work hours may result in reduced risk of sharps-related
      injuries among this group.

PMID- 17230383
TI  - Role of safety-engineered devices in preventing needlestick injuries in 32 French
      hospitals.
AB  - OBJECTIVES: To evaluate safety-engineered devices (SEDs) with respect to their
      effectiveness in preventing needlestick injuries (NSIs) in healthcare settings
      and their importance among other preventive measures. DESIGN: Multicenter
      prospective survey with a 1-year follow-up period during which all incident NSIs
      and their circumstances were reported. Data were prospectively collected during a
      12-month period from April 1999 through March 2000. The procedures for which the
      risk of NSI was high were also reported 1 week per quarter to estimate procedure
      specific NSI rates. Device types were documented. Because SEDs were not in use
      when a similar survey was conducted in 1990, their impact was also evaluated by
      comparing findings from the recent and previous surveys. SETTING: A total of 102
      medical units from 32 hospitals in France. PARTICIPANTS: A total of 1,506 nurses
      in medical or intensive care units. RESULTS: A total of 110 NSIs occurring during
      at-risk procedures performed by nurses were documented. According to data from
      the 2000 survey, use of SEDs during phlebotomy procedures was associated with a
      74% lower risk (P<.01). The mean NSI rate for all relevant nursing procedures was
      estimated to be 4.72 cases per 100,000 procedures, for a 75% decrease since 1990
      (P<.01); however, the decrease in NSI rates varied considerably according to
      procedure type. Between 1990 and 2000, decreases in the NSI rates for each
      procedure were strongly correlated with increases in the frequency of SED use
      (r=0.88; P<.02). CONCLUSION: In this French hospital network, the use of SEDs was
      associated with a significantly lower NSI rate and was probably the most
      important preventive factor.

PMID- 17230384
TI  - Prevalence and risk factors for bloodborne exposure and infection in correctional
      healthcare workers.
AB  - OBJECTIVE: To determine the prevalence and risk factors for bloodborne exposure
      and infection in correctional healthcare workers (CHCWs).Design. Cross-sectional
      risk assessment study with a confidential questionnaire and serological testing
      performed during 1999-2000. SETTING: Correctional systems in 3 states. RESULTS:
      Among 310 participating CHCWs, the rate of percutaneous injury (PI) was 32 PIs
      per 100 person-years overall and 42 PIs per 100 person-years for CHCWs with
      clinical job duties. Underreporting was common, with only 25 (49%) of 51 PIs
      formally reported to the administration. Independent risk factors for
      experiencing PI included being age 45 or older (adjusted odds ratio [aOR], 2.41
      [95% confidence interval (CI), 1.31-4.46]) and having job duties that involved
      needle contact (aOR, 3.70 [95% CI, 1.28-10.63]) or blood contact (aOR, 5.05 [95%
      CI, 1.45-17.54]). Overall, 222 CHCWs (72%) reported having received a primary
      hepatitis B vaccination series; of these, 150 (68%) tested positive for anti
      hepatitis B surface antigen, with negative results significantly associated with
      receipt of last dose more than 5 years previously. Serologic markers of hepatitis
      B virus infection were identified in 31 individuals (10%), and the prevalence of
      hepatitis C virus infection was 2% (n=7). The high hepatitis B vaccination rate
      limited the ability to identify risk factors for infection, but hepatitis C virus
      infection correlated with community risk factors only. CONCLUSION: Although the
      wide coverage with hepatitis B vaccination and the decreasing rate of hepatitis C
      virus infection in the general population are encouraging, the high rate of
      exposure in CHCWs and the lack of exposure documentation are concerns. Continued
      efforts to develop interventions to reduce exposures and encourage reporting
      should be implemented and evaluated in correctional healthcare settings. These
      interventions should address infection control barriers unique to the
      correctional setting.

PMID- 17230385
TI  - Validation of surgical site infection surveillance in the Netherlands.
AB  - OBJECTIVES: To describe how continuous validation of data on surgical site
      infection (SSI) is being performed in the Dutch National Nosocomial Infection
      Surveillance System (Preventie Ziekenhuisinfecties door Surveillance [PREZIES]),
      to assess the quality and accuracy of the PREZIES data, and to present the
      corresponding outcomes of the assessment. DESIGN: Mandatory, 1-day on-site
      validation visit to participating hospitals every 3 years. The process of
      surveillance, including the quality of the method of data collection, is
      validated by means of a structured interview. The use of SSI criteria is
      validated by review of medical records, with the judgment of the validation team
      as the criterion standard. SETTING: Hospitals participating in PREZIES. RESULTS:
      During 1999-2004, the validation team visited 40 hospitals and reviewed 859
      medical charts. There was no deviation between reports of SSI by infection
      control professionals and findings by the PREZIES validation team at 30 hospitals
      and 1 deviation in each of 10 hospitals; the positive predictive value was 0.97,
      and the negative predictive value was 0.99. The validation team often gave advice
      to the hospital, aimed at perfecting the process of surveillance. On 2 occasions,
      data were removed from the PREZIES database after the validation visit revealed
      deviations from the SSI surveillance protocol that could have resulted in
      nonrepresentative SSI rate data. CONCLUSIONS: PREZIES is confident that the
      assembled Dutch SSI surveillance data are reliable and robust and are
      sufficiently accurate to be used as a reference for interhospital comparison.
      PREZIES will continue performing on-site validation visits, to improve the
      process of surveillance and ensure the reliability of the surveillance data.

PMID- 17230386
TI  - Multicenter intervention program to increase adherence to hand hygiene
      recommendations and glove use and to reduce the incidence of antimicrobial
      resistance.
AB  - OBJECTIVE: To determine whether a multimodal intervention could improve adherence
      to hand hygiene and glove use recommendations and decrease the incidence of
      antimicrobial resistance in different types of healthcare facilities. DESIGN:
      Prospective, observational study performed from October 1, 1999, through December
      31, 2002. We monitored adherence to hand hygiene and glove use recommendations
      and the incidence of antimicrobial-resistant bacteria among isolates from
      clinical cultures. We evaluated trends in and predictors for adherence and
      preferential use of alcohol-based hand rubs, using multivariable analyses.
      SETTING: Three intervention hospitals (a 660-bed acute and long-term care
      hospital, a 120-bed community hospital, and a 600-bed public teaching hospital)
      and a control hospital (a 700-bed university teaching hospital).Intervention. At
      the intervention hospitals, we introduced or increased the availability of
      alcohol-based hand rub, initiated an interactive education program, and developed
      a poster campaign; at the control hospital, we only increased the availability of
      alcohol-based hand rub. RESULTS: We observed 6,948 hand hygiene opportunities.
      The frequency of hand hygiene performance or glove use significantly increased
      during the study period at the intervention hospitals but not at the control
      hospital; the maximum quarterly frequency of hand hygiene performance or glove
      use at intervention hospitals (74%, 80%, and 77%) was higher than that at the
      control hospital (59%). By multivariable analysis, preferential use of alcohol
      based hand rubs rather than soap and water for hand hygiene was more likely among
      workers at intervention hospitals compared with nonintervention hospitals
      (adjusted odds ratio, 4.6 [95% confidence interval, 3.3-6.4]) and more likely
      among physicians (adjusted odds ratio, 1.4 [95% confidence interval, 1.2-1.8])
      than among nurses at intervention hospitals. A significantly reduced incidence of
      antimicrobial-resistant bacteria among isolates from clinical culture was found
      at a single intervention hospital, which had the greatest increase in the
      frequency of hand hygiene performance. CONCLUSIONS: During a 3-year period, a
      multimodal intervention program increased adherence to hand hygiene
      recommendations, especially to the use of alcohol-based hand rubs. In one
      hospital, a concomitant reduction was found in the incidence of antimicrobial
      resistant bacteria among isolates from clinical cultures.

PMID- 17230387
TI  - Introducing alcohol-based hand rub for hand hygiene: the critical need for
      training.
AB  - BACKGROUND: Use of an alcohol-based hand rub for hand hygiene has recently been
      recommended by the Centers for Disease Control and Prevention. However, the
      proper technique for using hand rub has not been well described and is not
      routinely taught in hospitals. OBJECTIVE: To evaluate the impact of training on
      proper technique as outlined by the European Standard for testing alcohol-based
      hand rubs (European Norm 1500) in a clinical study. DESIGN, SETTING, AND
      PATIENTS: Prospective study including 180 healthcare workers (HCWs) in a 450-bed,
      university-affiliated geriatric hospital where alcohol-based hand rub was
      introduced in the late 1970s. INTERVENTION: Structured training program in hand
      hygiene with alcohol-based hand rub. Technique for using hand rub was tested by
      the addition of a fluorescent dye to the disinfectant and the number of areas
      missed was quantified by a validated visual assessment method. In addition, the
      number of bacteria eradicated was estimated by calculating the difference between
      the log(10) number of colony-forming units (cfu) of bacteria on the fingertips
      before and after the procedure, and reported as reduction factor (RF). MAIN
      OUTCOME MEASURE: Log(10) cfu bacterial counts on fingertips before and after
      training in the appropriate technique for using hand rub. RESULTS: At baseline,
      only 31% of HCWs used proper technique, yielding a low RF of 1.4 log(10) cfu
      bacterial count. Training improved HCW compliance to 74% and increased the RF to
      2.2 log(10) cfu bacterial count, an increase of almost 50% (P<.001). Several
      factors, such as applying the proper amount of hand rub, were significantly
      associated with the increased RF. CONCLUSION: These results demonstrate that
      education on the proper technique for using hand rub, as outlined in EN 1500, can
      significantly increase the degree of bacterial killing.

PMID- 17230388
TI  - Performance of the national nosocomial infections surveillance risk index in
      predicting surgical site infection in australia.
AB  - BACKGROUND: The Victorian Hospital Acquired Infection Surveillance System
      (VICNISS) hospital-acquired infection surveillance system was established in 2002
      in Victoria, Australia, and collates surgical site infection (SSI) surveillance
      data from public hospitals in Australia. OBJECTIVE: To evaluate the association
      between the US National Nosocomial Infections Surveillance (NNIS) system's risk
      index and SSI rates for 7 surgical procedures. METHODS: SSI surveillance was
      performed with NNIS definitions and methods for surgical procedures performed
      between November 2002 and September 2004. Correlations were assessed using the
      Goodman-Kruskal gamma statistic. RESULTS: Data were submitted for the following
      numbers of procedures: appendectomy, 545; coronary artery bypass graft (CABG),
      4,632; cholecystectomy, 1,001; colon surgery, 623; cesarean section, 4,857; hip
      arthroplasty, 3,825; and knee arthroplasty, 2,416. NNIS risk index and increasing
      SSI rate were moderately well correlated for appendectomy ( gamma =0.55), colon
      surgery ( gamma =0.48), and cesarean section ( gamma =0.42). A fairly positive
      correlation was found for cholecystectomy ( gamma =0.17), hip arthroplasty (
      gamma =0.2), and knee arthroplasty ( gamma =0.16). However, for CABG surgery, a
      poor association was found ( gamma =0.02). CONCLUSIONS: The NNIS risk index was
      positively correlated with an increasing SSI rate for all 7 procedures; the
      strongest correlation was found for appendectomy, cesarean section, and colon
      surgery, and the poorest correlation was found for CABG surgery. We believe that
      risk stratification with the NNIS risk index is appropriate for comparison of
      data for most procedures and superior to use of no risk adjustment. However, for
      some procedures, particularly CABG, further studies of alternative risk indexes
      are needed to better stratify patients.

PMID- 17230389
TI  - Filamentous fungi in a tertiary care hospital: environmental surveillance and
      susceptibility to antifungal drugs.
AB  - OBJECTIVE: To evaluate filamentous fungi with respect to environmental load and
      potential drug resistance in a tertiary care teaching hospital. DESIGN: Monthly
      survey in 2 buildings of the hospital during a 12-month period. SETTING:
      Hippokration Hospital in Thessaloniki, Greece. METHODS: Air, surface, and tap
      water sampling was performed in 4 departments with high-risk patients. As
      sampling sites, the solid-organ transplantation department and the hematology
      department (in the older building) and the pediatric oncology department and the
      pediatric intensive care unit (in the newer building) were selected. RESULTS:
      From January to May of 2000, the fungal load in air (FLA) was low, ranging from 0
      to 12 colony-forming units (cfu) per m(3) in both buildings. During the summer
      months, when high temperature and humidity predominate, the FLA increased to 4-56
      cfu/m(3). The fungi commonly recovered from culture of air specimens were
      Aspergillus niger (25.9%), Aspergillus flavus (17.7%), and Aspergillus fumigatus
      (12.4%). Non-Aspergillus filamentous fungi, such as Zygomycetes and Dematiaceous
      species, were also recovered. The pediatric intensive care unit had the lowest
      mean FLA (7.7 cfu/m(3)), compared with the pediatric oncology department (8.7
      cfu/m(3)), the solid-organ transplantation department (16.1 cfu/m(3)), and the
      hematology department (22.6 cfu/m(3)). Environmental surfaces were swabbed, and
      62.7% of the swab samples cultured yielded filamentous fungi similar to the fungi
      recovered from air but with low numbers of colony-forming units. Despite vigorous
      sampling, culture of tap water yielded no fungi. The increase in FLA observed
      during the summer coincided with renovation in the building that housed the solid
      organ transplantation and hematology departments. All 54 Aspergillus air isolates
      randomly selected exhibited relatively low minimum inhibitory or effective
      concentrations for amphotericin B, itraconazole, voriconazole, posaconazole,
      micafungin, and anidulafungin. CONCLUSION: Air and surface fungal loads may vary
      in different departments of the same hospital, especially during months when the
      temperature and humidity are high. Environmental Aspergillus isolates are
      characterized by lack of resistance to clinically important antifungal agents.

PMID- 17230390
TI  - Nursing home outbreak of invasive group a streptococcal infections caused by 2
      distinct strains.
AB  - OBJECTIVE: To identify factors contributing to a cluster of deaths from invasive
      group A streptococcus (GAS) infection in a nursing home facility and to prevent
      additional cases. DESIGN: Outbreak investigation. SETTING: A 146-bed nursing home
      facility in northern Nevada. METHODS: We defined a case as the isolation of GAS
      from a normally sterile site in a resident of nursing home A. To identify case
      patients, we reviewed resident records from nursing home A, the local hospital,
      and the hospital laboratory. We obtained oropharyngeal and skin lesion swabs from
      staff and residents to assess GAS colonization and performed emm typing on
      available isolates. To identify potential risk factors for transmission, we
      performed a cohort study and investigated concurrent illness among residents and
      surveyed staff regarding infection control practices. RESULTS: Six residents met
      the case patient definition; 3 (50%) of them died. Among invasive GAS isolates
      available for analysis, 2 distinct strains were identified: emm11 (3 isolates)
      and emm89 (2 isolates). The rate of GAS carriage was 6% among residents and 4%
      among staff; carriage isolates were emm89 (8 isolates), emm11 (2 isolates), and
      emm1 (1 isolate). Concurrently, 35 (24%) of the residents developed a respiratory
      illness of unknown etiology; 41% of these persons died. Twenty-one (30%) of the
      surveyed employees did not always wash their hands before patient contacts, and
      27 (38%) did not always wash their hands between patient contacts. CONCLUSIONS:
      Concurrent respiratory illness likely contributed to an outbreak of invasive GAS
      infection from 2 strains in a highly susceptible population. This outbreak
      highlights the importance of appropriate infection control measures, including
      respiratory hygiene practices, in nursing home facilities.

PMID- 17230391
TI  - Impact of severe acute respiratory syndrome care on the general health status of
      healthcare workers in taiwan.
AB  - BACKGROUND: The impact of the outbreak of severe acute respiratory syndrome
      (SARS) was enormous, but few studies have focused on the infectious and general
      health status of healthcare workers (HCWs) who treated patients with SARS.
      DESIGN: We prospectively evaluated the general health status of HCWs during the
      SARS epidemic. The Medical Outcome Study Short-Form 36 Survey was given to all
      HCWs immediately after caring for patients with SARS and 4 weeks after self
      quarantine and off-duty shifts. Tests for detection of SARS coronavirus antibody
      were performed for HCWs at these 2 time points and for control subjects during
      the SARS epidemic. SETTING: Tertiary care referral center in Taipei, Taiwan.
      SUBJECTS: Ninety SARS-care task force members (SARS HCWs) and 82 control
      subjects. RESULTS: All serum specimens tested negative for SARS antibody. Survey
      scores for SARS HCWs immediately after care were significantly lower than those
      for the control group (P<.05 by the t test) in 6 categories. Vitality, social
      functioning, and mental health immediately after care and vitality and mental
      health after self-quarantine and off-duty shifts were among the worst subscales.
      The social functioning, role emotional, and role physical subscales significantly
      improved after self-quarantine and off-duty shifts (P<.05, by paired t test). The
      length of contact time (mean number of contact-hours per day) with patients with
      SARS was associated with some subscales (role emotional, role physical, and
      mental health) to a mild extent. The total number of contact-hours with
      symptomatic patients with SARS was a borderline predictor (adjusted R2=0.069;
      P=.038) of mental health score. CONCLUSIONS: The impact of the SARS outbreak on
      SARS HCWs was significant in many dimensions of general health. The vitality and
      mental health status of SARS HCWs 1 month after self-quarantine and off-duty
      shifts remained inferior to those of the control group.

PMID- 17230392
TI  - Risk of hepatitis B virus transmission via dental handpieces and evaluation of an
      anti-suction device for prevention of transmission.
AB  - We evaluated the risk of hepatitis B virus (HBV) transmission via dental
      handpieces and the effects of an anti-suction device in preventing HBV
      contamination. The results of our study show that under certain conditions, HBV
      transmission can occur when an anti-suction device is used during dental
      procedures. We conclude that such devices may decrease contamination, but do not
      eliminate it.

PMID- 17230393
TI  - Knowledge, attitudes, and practice of iranian dentists with regard to HIV-related
      disease.
AB  - Of 369 registered dentists in Fars province in Iran, 309 (83.7%) responded to a
      survey regarding knowledge, attitudes, and practices related to human
      immunodeficiency virus (HIV) infection. The level of knowledge was low and was
      correlated with years in practice, hours worked per week, and whether additional
      work in a governmental dental office was performed; only the last was
      significantly associated with adherence to relevant infection control
      recommendations.

PMID- 17230394
TI  - Effect of education on hand hygiene beliefs and practices: a 5-year program.
AB  - To evaluate infection control and hand hygiene understanding at 3 public
      hospitals, we surveyed 4,345 healthcare workers (HCWs) 3 times during a 5-year
      infection control intervention. The preference for the use of alcohol hand rub
      for hand hygiene increased dramatically; in nurses, it increased from 14% to 34%;
      in physicians, 4.3% to 51%; and in allied HCWs, 12% to 44%. Study year, infection
      control interactive education-session attendance, infection control knowledge,
      and being a physician or allied HCW independently predicted a preference for
      alcohol hand rub.

PMID- 17230395
TI  - Coating urinary catheters with an avirulent strain of Escherichia coli as a means
      to establish asymptomatic colonization.
AB  - We investigated whether insertion of urinary catheters that had been coated with
      Escherichia coli HU2117 could establish bladder colonization with this
      nonvirulent organism. Ten of 12 subjects were successfully colonized for 14 days
      or more. The rate of symptomatic UTI during colonization was 0.15 per 100 patient
      days.

PMID- 17230396
TI  - Increasing incidence of sterile-site infections due to non-multidrug-resistant,
      oxacillin-resistant Staphylococcus aureus among hospitalized patients.
AB  - The incidence of community-associated, healthcare-associated, and hospital
      acquired sterile-site infections due to methicillin-resistant Staphylococcus
      aureus (MRSA) isolates and the susceptibility of the isolates to non- beta 
      lactam antibiotics were evaluated for 549 hospitalized patients during a 3-year
      period. The incidence of community-associated MRSA infection increased
      significantly. The annual percentage of MRSA isolates from cases of healthcare
      associated and hospital-acquired infection that were susceptible to 3 or more non
      beta -lactam antibiotics increased significantly.

PMID- 17230397
TI  - Large outbreak of infection and colonization with gram-negative pathogens
      carrying the metallo- beta -lactamase gene blaIMP-4 at a 320-bed tertiary
      hospital in Australia.
AB  - A large outbreak of infection and colonization with multiple genera of gram
      negative bacilli carrying the metallo- beta -lactamase gene bla(IMP-4) occurred
      in a 36-bed intensive care unit at a tertiary hospital in Australia. The
      organisms emerged rapidly, caused severe infections, and contributed to
      mortality. Controlling the spread of these organisms remains a challenge for all
      staff involved.

PMID- 17230398
TI  - Predicting resource partitioning and community organization of filter-feeding
      dabbling ducks from functional morphology.
AB  - Resource partitioning due to interspecific differences in phenotype is a key
      component of ecological and evolutionary theory, but the relationship between
      morphology and resource use is poorly understood for most species. In addition,
      ecologists often assume that morphological differences cause distinct resource
      preferences between species. Using mechanistic models that combine bill
      morphology and kinetics, I show that filter-feeding dabbling ducks face a
      morphology-mediated trade-off between particle size selection and water
      filtration rate. When detritus is absent, mallards (Anas platyrhynchos) and
      northern shovelers (Anas clypeata) should maximize their intake rates and exhibit
      high overlap in prey size. When prey and detritus co-occur, species should
      separate prey from detritus by size, leading to reduced intake rates and size
      based prey partitioning. Models for both species correctly predicted variation in
      water filtration rates, particle retention probabilities, and prey ingestion
      rates due to variation in prey size, the presence of detritus, and experimental
      modification of bill morphology. Because species have both shared and distinct
      resource preferences, duck communities should exhibit strong density-dependent
      niche shifts (i.e., centrifugal dynamics), a finding that contradicts previous
      studies that assumed that ducks have distinct resource preferences only.
      Centrifugal dynamics may be widespread among filter feeders because of the common
      cost of separating prey from detritus. 

PMID- 17230399
TI  - Patch aging and the S-Allee effect: breeding system effects on the demographic
      response of plants to habitat fragmentation.
AB  - We used empirical and modeling approaches to examine effects of plant breeding
      systems on demographic responses to habitat fragmentation. Empirically, we
      investigated effects of local flowering plant density on pollination and of
      population size on mate availability in a common, self-incompatible purple
      coneflower, Echinacea angustifolia, growing in fragmented prairie habitat.
      Pollination and recruitment increased with weighted local density around
      individual flowering plants. This positive density dependence is an Allee effect.
      In addition, mean mate compatibility between pairs of plants increased with
      population size. Based on this empirical study, we developed an individual-based,
      spatially explicit demographic model that incorporates autosomal loci and an S
      locus. We simulated habitat fragmentation in populations identical except for
      their breeding system, self-incompatible (SI) or self-compatible (SC). Both
      populations suffered reduced reproduction in small patches because of scarcity of
      plants within pollination distance (potential mates) and inbreeding depression.
      But SI species experienced an additional, genetic contribution to the Allee
      effect (S-Allee effect) caused by allele loss at the S locus, which reduces mate
      availability, thereby decreasing reproduction. The strength of the S-Allee effect
      increases through time (i.e., patches age) because random genetic drift reduces S
      allele richness. We investigate how patch aging influences extinction and discuss
      how the S-Allee effect influences communities in fragmented habitat. 

PMID- 17230400
TI  - Phylogenetic measures of biodiversity.
AB  - We developed a theoretical framework based on phylogenetic comparative methods to
      integrate phylogeny into three measures of biodiversity: species variability,
      richness, and evenness. These metrics can be used in conjunction with permutation
      procedures to test for phylogenetic community structure. As an illustration, we
      analyzed data on the composition of 58 lake fish communities in Wisconsin. The
      fish communities showed phylogenetic underdispersion, with communities more
      likely to contain closely related species. Using information about differences in
      environmental characteristics among lakes, we demonstrated that phylogenetic
      underdispersion in fish communities was associated with environmental factors.
      For example, lakes with low pH were more likely to contain species in the same
      clade of acid-tolerant species. Our metrics differ from existing metrics used to
      calculate phylogenetic community structure, such as net relatedness index and
      Faith's phylogenetic diversity. Our metrics have the advantage of providing an
      integrated and easy-to-understand package of phylogenetic measures of species
      variability, richness, and evenness with well-defined statistical properties.
      Furthermore, they allow the easy evaluation of contributions of individual
      species to different aspects of the phylogenetic organization of communities.
      Therefore, these metrics should aid with the incorporation of phylogenetic
      information into strategies for understanding biodiversity and its conservation. 

PMID- 17230401
TI  - The causes of evolutionary radiations in archipelagoes: passerine birds in the
      Lesser Antilles.
AB  - To investigate why some lineages undergo evolutionary radiation, we compare the
      passerine avifaunas of the Hawaiian and Galapagos archipelagoes, which have
      supported well-known radiations of birds, with those of the Lesser Antilles,
      which have not. We focus on four steps required for the buildup of diversity
      through allopatric speciation and secondary sympatry: genetic divergence in
      isolation, persistence of island populations, recolonization of source islands,
      and ecological compatibility in secondary sympatry. Analysis of genetic
      divergence among island populations in the Lesser Antilles reveals evidence of
      both prolonged independent evolution and re-expansion of differentiated island
      populations through the archipelago but little evidence of secondary sympatry of
      divergent genetic lineages. Archipelagoes with high rates of colonization from
      continental or nearby large-island sources might fail to promote evolutionary
      radiations because colonists fill ecological space and constrain diversification
      through competition. However, morphological analysis demonstrated similar
      divergence between allopatric populations in species in Hawaii, Galapagos, and
      the Lesser Antilles, although the rate of divergence between secondarily
      sympatric species evidently is more rapid in Hawaii and the Galapagos.
      Alternatively, endemic buildup of diversity might be facilitated by the relative
      absence of pathogens in Hawaii and Galapagos that otherwise could prevent the
      secondary sympatry of populations owing to disease-mediated competition. 

PMID- 17230402
TI  - Maintaining diversity in an ant community: modeling, extending, and testing the
      dominance-discovery trade-off.
AB  - Ant communities often consist of many species with apparently similar niches. We
      present a mathematical model of the dominance-discovery trade-off, the trade-off
      between the abilities to find and to control resources, showing that it can in
      principle facilitate the coexistence of large numbers of species. Baiting studies
      of dominance and discovery abilities in an ant community from the Chiricahua
      Mountains of Arizona indicate that real communities fail to fit the assumptions
      of the simple model in several ways: (1) dominance depends on the size of the
      food resource; (2) for some ants, dominance depends on the presence or absence of
      specialist parasitoids; (3) pairwise dominance is not an all-or-nothing trait;
      and (4) a consistent negative relationship between pairwise differences in per
      capita discovery rates and dominance can be detected for only one bait type.
      Extended models incorporating these factors successfully predict the coexistence
      of five of the six most abundant members of this community but fail to accurately
      predict their relative abundances. Sensitivity analysis indicates that each
      complicating factor enhances the extent of coexistence. 

PMID- 17230403
TI  - Cues for eavesdroppers: do frog calls indicate prey density and quality?
AB  - Predators and parasites that eavesdrop on the mating signals of their prey often
      preferentially select individuals within a prey/host species that produce
      specific cues. Mechanisms driving such signal preferences are poorly understood.
      In the tungara frog Physalaemus pustulosus, conspecific females, frog-eating
      bats, and blood-sucking flies all prefer complex to simple mating calls. In this
      study we assess the natural signal variation in choruses in the wild and test two
      hypotheses for why eavesdroppers prefer complex calls: (1) prey quality: complex
      calls indicate better quality of prey/host, and (2) prey density: complex calls
      indicate higher prey/host density. Call complexity is not correlated with frog
      length, mass, or body condition, but it does signal higher abundance of
      prey/host. Thus, increased effectiveness of attack may have played a role
      favoring the preference for complex calls in eavesdropping heterospecifics. 

PMID- 17230404
TI  - Is Epstein-Barr virus transmitted sexually?

PMID- 17230405
TI  - Anthrax: from antiquity to answers.

PMID- 17230406
TI  - A study of risk factors for acquisition of Epstein-Barr virus and its subtypes.
AB  - BACKGROUND: Risk factors for primary infection with Epstein-Barr virus (EBV) and
      its subtypes have not been fully investigated. METHODS: Questionnaires and serum
      samples from a total of 2006 students who entered Edinburgh University in 1999
      2000 were analyzed to examine risk factors for EBV seropositivity, both overall
      and by EBV type. RESULTS: The prevalence of EBV seropositivity was significantly
      increased among females, older students, those who had lived in tropical
      countries, those with siblings, and those who were sexually active, particularly
      if they had had numerous sex partners. Risk was lower (1) among students who
      always used a condom than among those who had sexual intercourse without one and
      (2) among female oral-contraceptive users than among sexually active nonusers.
      Risk factors for type 1 EBV infection were similar to those for EBV overall. No
      associations were found between nonsexual risk factors and type 2 infection.
      Sexual activity increased the risk of type 2 infection, but the increase in risk
      with number of sex partners was less consistent than for type 1 infections. Dual
      infection was uncommon, but the patterns of risk appeared to be similar to those
      of type 1 infection. CONCLUSION: This study provides further evidence that EBV
      may be sexually transmitted and some suggestion that the risk factors for type 1
      and type 2 infection differ.

PMID- 17230407
TI  - Serum IgA antibodies to Epstein-Barr virus (EBV) early lytic antigens are present
      in primary EBV infection.
AB  - Primary Epstein-Barr virus (EBV) infection is characterized by the presence of
      IgM antibodies to viral capsid antigen and the absence of antibodies to EB
      nuclear antigen. Here, using a flow cytometry-based assay, we investigated
      whether IgA antibodies are a marker for primary infection. Serum IgA antibodies
      in 15 individuals with primary EBV infection reacted with 15%-55.6% of HH514-16
      Burkitt lymphoma cells expressing early lytic antigens (EAs), whereas IgA
      antibodies in serum samples from 15 healthy EBV-seropositive individuals reacted
      with 0.02%-2% of cells with EAs (P<.0001). IgA antibodies in primary infection
      were directed against the Bam Z Epstein-Barr replication activator (ZEBRA)
      (BZLF1) and diffuse EA (BMRF1) EAs. Thus, IgA antibodies to EBV EAs are produced
      during primary EBV infection and are likely to be stimulated as a result of lytic
      EBV replication in mucosal sites. Detection of IgA antibodies to EA may be
      developed into a diagnostic tool for primary EBV infection.

PMID- 17230408
TI  - Predictors of herpes simplex virus type 2 prevalence and incidence among bar and
      hotel workers in Moshi, Tanzania.
AB  - BACKGROUND: Herpes simplex virus (HSV) type 2 increases the risk of human
      immunodeficiency virus (HIV) infection, and, in regions with high prevalence of
      both viruses, control of HSV-2 may be an effective method of HIV prevention.
      Identification of modifiable factors for prevention of HSV-2 infection is
      essential. We conducted this study among female bar and hotel workers in Moshi,
      Tanzania. METHODS: Factors associated with prevalent infection were examined
      among 1039 women. Predictors of incident infection were examined among 360 women
      initially HSV-2 negative, with at least 1 follow-up visit. RESULTS: HSV-2
      prevalence was 56.3% (95% confidence interval [CI], 53.3%-59.3%). Only 2.5% of
      women able to name a sexually transmitted infection named herpes. Incidence was
      14.2 cases/100 person-years (95% CI, 10.5-18.8 cases/100 person-years). Incident
      HSV-2 infection was independently associated with HIV infection, younger age of
      sexual initiation, ethnicity, alcohol consumption, and having a male partner with
      other sexual partners. CONCLUSIONS: The occurrence of HSV-2 is high in this
      population, but knowledge is low. Development of education programs to increase
      awareness of HSV-2 is critical. The control of both HSV-2 and HIV infections is a
      major public health priority in Moshi. Prevention interventions in this and other
      high prevalence populations might most effectively target younger women, before
      initiation of sexual activity.

PMID- 17230409
TI  - DNA sequence variability in isolates recovered from patients with postvaccination
      rash or herpes zoster caused by Oka varicella vaccine.
AB  - Little is known about the pathogenic potential of individual strains in the
      varicella vaccine. We analyzed genomic variation among specimens obtained from
      vaccine recipients with postvaccination rash or herpes zoster (HZ), focusing on
      polymorphisms between live attenuated varicella vaccine virus and wild-type
      varicella-zoster virus. Eleven of 18 postvaccination HZ specimens contained >1
      strain, and 7 of 18 appeared to be clonal. All 21 postvaccination rash specimens
      contained mixtures of vaccine strains. Four single-nucleotide polymorphisms
      (SNPs) consistently occurred in every isolate; all were polymorphisms in open
      reading frame (ORF) 62, and 2 confer amino acid substitutions in the immediate
      early protein 62. Four wild-type SNPs occurred in every isolate: one each
      occurred in ORF 10, ORF 21, ORF 62, and a noncoding region upstream of ORF 64.
      The frequencies of the remaining wild-type SNPs were variable, with the SNPs
      uniformly expressed (even in mixtures) in 20.5%-97.4% of isolates (mean
      frequency, 67.7%). No 2 clinical isolates had identical SNP profiles; as such,
      vaccine latency usually involves >1 strain.

PMID- 17230410
TI  - Age-related differences in pulmonary cytokine response to respiratory syncytial
      virus infection: modulation by anti-inflammatory and antiviral treatment.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the major cause of severe lower
      respiratory tract infection in infants and young children. Recently, RSV has also
      been recognized as a serious health risk in elderly individuals, but the
      pathogenesis of RSV infection in elderly individuals remains unknown. METHODS:
      Dynamics of pulmonary cytokine response (including interferon- gamma ,
      interleukin [IL]-4, IL-10, IL-6, monocyte chemoattractant protein-1, and growth
      regulated oncogene [GRO] mRNA) during acute RSV infection were investigated in
      young (<2 months old) and aged (>9 months old) cotton rats (Sigmodon hispidus).
      Therapeutic treatments that diminish viral replication (antiviral antibody) and
      pulmonary inflammation (anti-inflammatory corticosteroid) in RSV-infected cotton
      rats were used to evaluate the contribution of virus replication and inflammation
      to the development of RSV disease with respect to age. RESULTS: The time of the
      peak expression of the majority of cytokines was shifted with respect to age.
      Antiviral and anti-inflammatory treatments had a similar effect on cytokine
      expression in aged and young cotton rats. GRO mRNA transcripts were more abundant
      in the lungs of aged cotton rats. CONCLUSIONS: The present study reports an age
      related delay in the pulmonary cytokine response to RSV and an imbalance in
      chemokine production with respect to age and underscores different components of
      RSV pathogenesis with respect to their molecular signature.

PMID- 17230411
TI  - Hepatitis C virus coinfection and superinfection.
AB  - A hallmark of RNA viruses is their extreme genetic diversity. Within an
      individual, the hepatitis C virus (HCV) exists as a population of distinct but
      closely related viral variants, termed the "viral quasispecies." These variants
      may display divergent replicative capacity, cell tropism, immunologic escape, and
      antiviral-drug resistance. Coinfection with 2 or more distinct HCVs has been
      frequently documented. Moreover, several cases of HCV superinfection have been
      reported recently. However, few data are available regarding the clinical
      consequences of coinfection and superinfection, although these phenomena have
      important implications for HCV vaccine design and development, as well as for the
      efficacy of HCV therapeutic agents.

PMID- 17230412
TI  - Temporal trends in postseroconversion CD4 cell count and HIV load: the Concerted
      Action on Seroconversion to AIDS and Death in Europe Collaboration, 1985-2002.
AB  - OBJECTIVE: To determine whether early postseroconversion CD4 cell counts and
      human immunodeficiency virus (HIV) loads have changed over time. METHODS: Our
      analysis was based on 22 cohorts of people with known dates of seroconversion
      from Europe, Australia, and Canada (Concerted Action on Seroconversion to AIDS
      and Death in Europe Collaboration). We focused on individuals seroconverting
      between 1985 and 2002 who had the first CD4 cell count (n=3687) or HIV load
      (n=1584) measured within 2 years of seroconversion and before antiretroviral use.
      Linear regression models were used to assess time trends in postseroconversion
      CD4 cell count and HIV load. Trends in time to key thresholds were also assessed,
      using survival analysis. RESULTS: The overall median initial CD4 cell count was
      570 cells/ microL (interquartile range [IQR], 413-780 cells/ microL). The median
      initial HIV load was 35,542 copies/mL (IQR, 7600-153,050 copies/mL; on log(10)
      scale, 3.9-5.2 log(10) copies/mL). The postseroconversion CD4 cell count changed
      by an average of -6.33 cells/ microL/year (95% confidence interval [CI], -8.47 to
      -4.20 cells/ microL/year; P<.001), whereas an increase was observed in log(10)
      HIV load (+0.044 log(10) copies/mL/year; 95% CI, +0.034 to +0.053 log(10)
      copies/mL/year). These trends remained after adjusting for potential confounders.
      The probability of progressing to a CD4 cell count of <500 cells/ microL by 24
      months from seroconversion increased from 0.66 (95% CI, 0.63-0.69) for
      individuals who seroconverted before 1991 to 0.80 (95% CI, 0.75-0.84) for those
      who seroconverted during 1999-2002. CONCLUSION: These data suggest that, in
      Europe, there has been a trend of decrease in the early CD4 cell count and of
      increase in the early HIV load. Additional research will be necessary to
      determine whether similar trends exist in other geographical areas.

PMID- 17230414
TI  - Estimating the benefit of an HIV-1 vaccine that reduces viral load set point.
AB  - Vaccines designed to induce cell-mediated immune responses against human
      immunodeficiency virus (HIV)-1 are being developed. Such vaccines are unlikely to
      provide sterilizing immunity but may be associated with reduced viral set points
      after infection. We modeled the potential impact of a vaccine that reduces viral
      set point after infection, using natural history data from 311 HIV-1
      seroconverters. Log-normal parametric regression models were used to estimate the
      log median time to events of interest. Relative times were estimated for those
      with viral load set points of 30,000 copies/mL (reference group) versus those
      with lower viral set points. The time to key clinical events in the course of HIV
      1 disease progression was significantly extended for those with viral set points
      0.5-1.25 log(10) copies/mL lower than the reference group. By quantifying the
      anticipated clinical benefits associated with a reduction in viral set point,
      these findings support the use of virologic end points in HIV-1 vaccine trials.

PMID- 17230413
TI  - HIV-1 drug resistance in variants from the female genital tract and plasma.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) drug-resistance mutations
      may arise in a fraction of viral variants, and these variants may differ between
      compartments, including the genital tract and blood. METHODS: We studied 14 women
      with detectable HIV-1 in both the genital tract and plasma despite antiretroviral
      treatment. We obtained HIV-1 RNA sequences from 280 unique viral variants and
      then determined the resistance genotype and the predicted phenotype (Virtual
      Phenotype; Virco BVBA) of each variant. RESULTS: Eight patients (57%) displayed
      mutations conferring high-level HIV-1 drug resistance. Although we observed
      differences in specific mutations among viral variants, 13 of the 14 women showed
      highly concordant HIV-1 genotypic and predicted phenotypic resistance patterns in
      the 2 compartments. In 1 patient, resistance mutations appeared only in plasma;
      all variants in her genital tract, which displayed a low viral load, were
      susceptible. CONCLUSIONS: These data suggest that, for the majority of women,
      determination of HIV-1 drug resistance in the plasma will approximate the drug
      resistance pattern in the genital tract. Analysis of individual variants enabled
      us to identify minority species bearing distinctive linked mutations, which may
      serve as a source of novel resistance genotypes. These data are relevant to
      clinical management and the evolution of drug resistance.

PMID- 17230415
TI  - Simian immunodeficiency virus-induced lymphatic tissue fibrosis is mediated by
      transforming growth factor beta 1-positive regulatory T cells and begins in early
      infection.
AB  - In human immunodeficiency virus (HIV) infection, collagen deposition and fibrosis
      within the T cell zone disrupt the lymphatic tissue architecture, contributing to
      depletion of CD4(+) T cells and limiting immune reconstitution. We used relevant
      animal and in vitro models to investigate the kinetics and possible underlying
      mechanism(s) of this process. In the lymphatic tissue of simian immunodeficiency
      virus (SIV)-infected rhesus macaques, we observed parallel increases in immune
      activation, transforming growth factor (TGF) beta 1-positive regulatory T
      (T(reg)) cells, and collagen type I deposition by 7 days after inoculation,
      consistent with the hypothesis that early immune activation elicits a countering
      T(reg) cell response associated with TGF beta 1 expression and collagen
      deposition. In support of this hypothesis and the possible role of fibrosis in
      viral pathogenesis, we show (1) spatial colocalization and temporal concordance
      in levels of TGF beta 1(+) T(reg) cells and collagen deposition; (2) TGF beta
      1(+) inducible T(reg) cell stimulation of primary lymphatic tissue fibroblasts to
      produce collagen type I in vitro; and (3) high levels of immune activation, TGF
      beta 1(+) T(reg) cells, and collagen deposition in pathogenic SIV infection of
      macaques, in contrast to apathogenic SIV infection in sooty mangabeys in which
      levels of immune activation, TGF beta 1(+) T(reg) cells, and collagen deposition
      were low. We thus conclude that the response of TGF beta 1(+) T(reg) cells to
      immune activation in early SIV/HIV infection is a double-edged sword: TGF beta
      1(+) T(reg) cells normally have a positive effect by limiting immunopathological
      and autoreactive immune responses, but they also have a negative effect by
      dampening the antiviral immune response and, as we show here, causing deleterious
      effects on CD4(+) T cell homeostasis by inducing collagen deposition in lymphatic
      tissues.

PMID- 17230416
TI  - Human T cell leukemia virus type 1 up-regulation after simian immunodeficiency
      virus-1 coinfection in the nonhuman primate.
AB  - The effects that human T cell leukemia virus (HTLV) type 1 and simian
      immunodeficiency virus (SIV) coinfection have on HTLV-1 dynamics and disease
      progression were tested in a nonhuman primate model. Seven rhesus macaques were
      experimentally inoculated with HTLV-1, and a persistent infection was
      established. Coinfection with SIV/smB670 resulted in increased HTLV-1 p19
      antigens in peripheral blood mononuclear cells and HTLV-1 proviral loads.
      Circulating CD2(+) and CD8(+) T lymphocytes increased over preinoculation levels,
      along with a progressive decrease in CD4(+) T cells, typical for terminal SIV
      disease. Finally documented was the striking emergence of up to 19% of HTLV
      associated "flower cell" lymphocytes in the circulation, as seen in patients with
      adult T cell leukemia/lymphoma. CD8(+)CD25(+) T cell subpopulation increases were
      positively correlated with flower cell appearance and suggested their possible
      role in this process. We conclude that SIV may have the potential to up-regulate
      HTLV-1 and disease expression.

PMID- 17230417
TI  - Bacillus anthracis edema and lethal toxin have different hemodynamic effects but
      function together to worsen shock and outcome in a rat model.
AB  - INTRODUCTION: To better define the contribution of edema toxins (ETx) and lethal
      toxins (LeTx) to shock with Bacillus anthracis, recombinant preparations of each
      were investigated alone or together in rats. METHODS AND RESULTS: Lethal dose
      ranges (0%-100% lethality) of ETx (200-800 microg/kg as a 24-h infusion) were
      higher than those of LeTx (12.5-200 microg/kg) (P<.0001). However, compared with
      LeTx, similarly lethal ETx doses produced earlier and greater reductions in mean
      blood pressure (MBP) and increased, rather than decreased, heart rate (HR) (P<.05
      for all). Combining either similar weight or lethal doses of ETx and LeTx
      increased the hazard ratio for death (log +/- standard error) similar to the sum
      calculated with the toxin's effects alone (2.6+/-1.1 observed vs. 2.9+/-1.0
      calculated for similar weight and 3.1+/-1.0 vs. 3.9+/-1.5 for similar lethal
      doses; P=.5 for both). Early (< or =10 h) and late during infusion, ETx and LeTx
      together also altered MBP and HR in patterns consistent with the sum of their
      individual effects. CONCLUSIONS: ETx was approximately 10 times less lethal than
      LeTx but produced greater hypotension and added to the latter's harmful effects.
      These findings suggest that it may be appropriate for antitoxin therapies for B.
      anthracis to target both ETx and LeTx.

PMID- 17230418
TI  - Hypersusceptibility to invasive pneumococcal infection in experimental sickle
      cell disease involves platelet-activating factor receptor.
AB  - Children with sickle cell disease have a 600-fold increased incidence of invasive
      pneumococcal disease. Platelet-activating factor receptor (PAFr) mediates
      pneumococcal invasion, and up-regulation of PAFr on chronically activated
      endothelia could contribute to increased bacterial invasion. Mice transplanted
      with sickle cell bone marrow developed more extensive infection, and 57% died,
      compared with 16% of wild-type mice. Histopathological analysis revealed that
      sickle cell mice expressed significantly more PAFr on endothelia and epithelia.
      Pharmacological blockade or genetic deletion of PAFr protected sickle cell mice
      from mortality. We conclude that PAFr plays an important role in
      hypersusceptibility to pneumococcal infection in sickle cell disease.

PMID- 17230419
TI  - Bordetella pertussis binds human C1 esterase inhibitor during the virulent phase,
      to evade complement-mediated killing.
AB  - C1 esterase inhibitor (C1inh) is a major inhibitor of several pathways of
      inflammation in humans. In this study, we show that virulent-phase cultures of
      Bordetella pertussis, the etiological agent for whooping cough, but not other
      Bordetella species specifically recruit C1inh from human serum. Using a
      spontaneous mutant of B. pertussis that was deficient in C1inh binding, we
      demonstrate that the ability of B. pertussis to acquire high levels of human
      C1inh and wild-type levels of serum resistance are well correlated, suggesting
      that, in addition to and independent of BrkA expression, acquisition of C1inh is
      vital to B. pertussis resistance to complement-mediated killing.

PMID- 17230420
TI  - Lung injury in vivax malaria: pathophysiological evidence for pulmonary vascular
      sequestration and posttreatment alveolar-capillary inflammation.
AB  - BACKGROUND: The mechanisms underlying lung injury in vivax malaria are not well
      understood. Inflammatory responses to Plasmodium falciparum and P. vivax, to our
      knowledge, have not previously been compared at an organ level. METHODS:
      Respiratory symptoms and physiological aspects were measured longitudinally in
      Indonesian adults with uncomplicated vivax (n=50) and falciparum (n=50) malaria.
      Normal values were derived from 109 control subjects. Gas transfer was
      partitioned into its alveolar-capillary membrane (D(M)) and pulmonary capillary
      vascular (V(C)) components, to characterize the site and timing of impaired gas
      transfer. RESULTS: Mean baseline V(C) volume was significantly reduced in vivax
      and falciparum malaria, improving with treatment in each species. Baseline D(M)
      function was not impaired in either species. The progressive deterioration in
      D(M) function after treatment was statistically significant in vivax malaria but
      not in uncomplicated falciparum malaria. Oxygen saturation deteriorated after
      treatment in vivax but improved in falciparum malaria. CONCLUSIONS: The baseline
      reduction in V(C) volume but not in D(M) function suggests encroachment on V(C)
      volume by parasitized erythrocytes and suggests that P. vivax-infected
      erythrocytes may sequester within the pulmonary microvasculature. Progressive
      alveolar-capillary dysfunction after treatment of vivax malaria is consistent
      with a greater inflammatory response to a given parasite burden in P. vivax
      relative to that in P. falciparum.

PMID- 17230421
TI  - Influence of consecutive-day blood sampling on polymerase chain reaction-adjusted
      parasitological cure rates in an antimalarial-drug trial conducted in Tanzania.
AB  - We assessed the influence that consecutive-day blood sampling, compared with
      single-day blood sampling, had on polymerase chain reaction (PCR)-adjusted
      parasitological cure after stepwise genotyping of merozoite surface proteins 2
      (msp2) and 1 (msp1) in 106 children in Tanzania who had uncomplicated falciparum
      malaria treated with either sulfadoxine-pyrimethamine or artemether-lumefantrine;
      78 of these children developed recurrent parasitemia during the 42-day follow-up
      period. Initial msp2 genotyping identified 27 and 33 recrudescences by use of
      single- and consecutive-day sampling, respectively; in subsequent msp1
      genotyping, 17 and 21 of these episodes, respectively, were still classified as
      recrudescences; these results indicate a similar sensitivity of the standard
      single-day PCR protocol--that is, 82% (27/33) and 81% (17/21), in both genotyping
      steps. Interpretation of PCR-adjusted results will significantly depend on
      methodology.

PMID- 17230422
TI  - Pharmacokinetics of antimony in children treated for leishmaniasis with meglumine
      antimoniate.
AB  - BACKGROUND: In some settings, the response to pentavalent antimonial therapy for
      leishmaniasis may be lower in children than in adults. We hypothesized that there
      are age-dependent pharmacokinetic differences of potential clinical relevance.
      METHODS: We compared the pharmacokinetics of antimony (Sb) in adults and 2 groups
      of children 3-6 years old who had cutaneous leishmaniasis treated with
      intramuscular meglumine antimoniate. Adults (n=9) and the first group of children
      (n=9) received 20 mg Sb/kg/day for 20 days; the second group of children (n=6)
      received 20 mg Sb/kg for 19 days and 30 mg Sb/kg on day 20. Drug exposure was
      assessed by the area under the 24-h time-concentration curve (AUC(0-24)) in
      plasma. RESULTS: Children (vs. adults) who received 20 mg/kg had a 42% lower
      AUC(0-24) (mean +/- SE, 111+/-7 vs. 190+/-10 mg x h/L, compared with adults;
      P<.001), a 16% lower peak concentration (32.7+/-0.9 vs. 38.8+/-2.1 mg/L; P=.04),
      and a 75% higher weight-adjusted clearance (0.185+/-0.013 vs. 0.106+/-0.006
      L/h/kg; P<.001). The 30 mg/kg dose in children increased the AUC(0-24) to 164+/
      10 mg x h/L and the peak concentration to 43.8+/-2.3 mg/L. CONCLUSIONS: Drug
      exposure is significantly lower in children than in adults treated with the same
      weight-adjusted regimen of meglumine antimoniate, which primarily stems from a
      higher antimony clearance rate.

PMID- 17230423
TI  - Evidence for quasi species in severe acute respiratory syndrome-associated
      coronavirus deletion mutants.

PMID- 17230424
TI  - [Forgotten youth--mentally ill adolescent criminals without developmental
      opportunities? On the legal project reforming the right to forensic admission to
      a psychiatric hospital].

PMID- 17230425
TI  - [Developmental aspects in expert testimony for juvenile court].
AB  - The history of German legislation resulting in the developmental orientation of
      juvenile court law (JCL) led to setting the minimum age of criminal
      responsibility at the age of 14, which places Germany within the average range
      compared to other EU countries, even though most skills regarding the discernment
      of right- or wrong-doing are developed in earlier stages of life. The requirement
      put by section sign 3 JCL that legal discernment be emotionally grounded and the
      necessity to explore context factors (family or group, specific situation) make
      psychiatric evaluation of adolescents in court a delicate task. It is
      indispensable that new findings in neurobiology be considered upon making an
      assessment of the individual neuro-developmental status. In contrast, an
      assessment according to section sign 105 JCL considers the overall development
      irrespective of the crime(s). Developmental issues regarding legal prognosis are
      discussed for some types of offences (homicide, sexual offences, arson).

PMID- 17230426
TI  - [Mental health disorders among handicapped children and youth].
AB  - Data on the prevalence of mental health disorders among children and youth with
      hearing disorders, blindness, physical handicaps or intellectual disabilities are
      reviewed. Problems in parent-child relations and issues in the development of
      social competence and social participation are discussed as risk factors for
      emotional social maladjustment. The differentiation between developmental
      problems resulting from the handicap and mental health problems is a challenging
      task in practice. Some conclusions for psychopathological assessment of
      handicapped children and youth are presented.

PMID- 17230427
TI  - [Frankfurt group social communication and interaction skills training for
      children and adolescents with autism spectrum disorders].
AB  - OBJECTIVE: Despite the recognition of the need for group-based training
      programmes for children and adolescents with autistic disorders, there are only
      very few specific German-speaking training programmes available. Since 2003, a
      structured group training programme on social skills for children and adolescents
      with high-functioning autism or Asperger syndrome has been developed and
      conducted at our department. The training programme focuses on the main deficits
      of those disorders. Thus, the primary goal is to improve communication and
      interaction skills. METHOD: Participants are children and adolescents without
      significant cognitive and language delays. Principles of intervention include
      structured formats, combination of theoretical and practical elements,
      predictable rules, consideration of individual difficulties, and sequential and
      progressive learning. Techniques range from structured games, the training of
      affect recognition, group activities, role play, team discussions, and feedback
      to homework using a newly designed manual on our group-based social skill
      training programme and curriculum. Generally, three groups of 5-7 participants
      each and of different age range (children, adolescents) meet weekly/biweekly for
      1-1.5 hours (excluding the holidays). Two trainers--who change during the
      programme--carry out each of the sessions. Trainers meet regularly with the
      parents to discuss experiences and to provide details of the programme. RESULTS:
      Acceptance by and satisfaction with the programme are high among participants, as
      is the mutual recognition of and tolerance of their respective problems. Both
      feedback from parents and trainers' clinical impressions indicate distinct
      improvement of verbalization and contact abilities. Participants seem to benefit
      particularly from role play. CONCLUSIONS: Qualtitative measures (impressions of
      the participants, their parents and their trainers with regard to change in
      behaviour skills) suggest mounting interaction, communication, and problem
      solving skills during the group treatment. An ongoing pilot evaluation also
      includes measurements of effects in everyday settings. Depending on the results,
      the training subsequently could be conducted and evaluated in groups with both
      pervasive developmental, as well as other psychiatric disorders.

PMID- 17230428
TI  - [Phenomenology and co-morbidity of childhood onset obsessive compulsive
      disorder].
AB  - OBJECTIVES: The goal of the study was to investigate the contents and comorbidity
      features of obsessive-compulsive disorder in children and adolescents. METHOD: 55
      patients (29 males, 26 females), mainly inpatients selected from university
      clinics for child and adolescent psychiatry (95%), were investigated. Structured
      diagnostic interviews were used to interview patients and their parents. RESULTS:
      The mean age of onset for obsessive-compulsive disorders was 11.3 years. In males
      the onset was slightly earlier than among females, but this difference was not
      significantly significant. Compulsions mostly referred to washing and cleaning,
      checking, repeating, ordering, and counting. Most frequently, obsessions included
      thought about contamination, catastrophes, sexuality, and aggression. According
      to parental reports, the rate of comorbidity was high (lifetime diagnosis: 69%,
      current diagnosis: 53%), with anxiety, depressive, hyperkinetic, conduct, and
      eating disorders being the most frequent co-morbid conditions. Obsessive
      compulsive symptoms were more intense in those patients who had a greater number
      of lifetime diagnoses of other psychiatric disorders. Comparing the rates found
      when structured interviews were carried out according to the study protocol to
      those for clinicians, clinicians were found to have diagnosed mixed obsessional
      thoughts and acts (presenting obsessional thoughts, as well as compulsive acts)
      less frequently. CONCLUSIONS: The results of this investigation are well in line
      with those of international studies on obsessive-compulsive disorders. The rates
      of disorders found were dependent on the diagnostic methods used. A potentially
      promising approach for further investigation is the sub-typing of patients
      according to symptom dimensions.

PMID- 17230429
TI  - [How well do parents and teachers' reports agree on behaviour problems in pre
      school-aged children?].
AB  - OBJECTIVES: The purpose of the present study is to examine the extent of parental
      and teacher agreement on behaviour problems in preschool-aged children. METHOD:
      Families were recruited from preschools in Braunschweig. In total, N=310 children
      aged three to six years were evaluated by their mothers and fathers and by their
      preschool teachers using the Child Behavior Checklist and the Caregiver-Teacher
      Report for ages 1(1)/(2) to 5. RESULTS: The inter-parental agreement on behaviour
      problems was high. Parents consistently reported more problem behaviour than did
      preschool teachers. The median of intra-class correlation between the evaluations
      by the mothers with those by the fathers was 0.65, and 0.18 (0.17) for parent
      teacher dyads. For the agreement between parents with respect to the
      borderline/clinical range a mean of kappa=0.41 was found, while there was no
      agreement between parents and teachers. CONCLUSIONS: The results are integrated
      into the literature, and implications, particularly those for clinical assessment
      procedures at preschool age, are discussed.

PMID- 17230430
TI  - [Young Investigators in Biological child and adolescent psychiatry (YIBcap)-
      insights after one year of networking].
AB  - Biological determinants of mental illness in children and adolescents, such as
      genetic predisposition, gene x environment interactions, structural or functional
      brain abnormalities, and endocrine dysfunction are poorly understood. We report
      here on the foundation of and first achievements by a network of young
      professionals in the area of child and adolescent psychiatry that fosters
      biological research. YIBcap--Young Investigators in Biological child and
      adolescent psychiatry was founded in December 2005 and currently comprises 33
      scientists from more than ten different German university hospitals, and seven
      internationally renowned senior advisors. Peer-to-peer support is provided by
      means of web-based communication software, regular meetings, workshops on
      research methods and fundraising, special symposia at scientific conferences,
      research collaborations, and career coaching. First multi-centre studies are
      planned. Increasingly positive results within the first year let us hope to be
      able to establish a forum that can contribute to improving scientific output and
      to encouraging young investigators in child and adolescent psychiatry.

PMID- 17230433
TI  - Identification of proteins directly from tissue: in situ tryptic digestions
      coupled with imaging mass spectrometry.
AB  - A novel method for on-tissue identification of proteins in spatially discrete
      regions is described using tryptic digestion followed by matrix-assisted laser
      desorption/ionization (MALDI) imaging mass spectrometry (IMS) with MS/MS
      analysis. IMS is first used to reveal the protein and peptide spatial
      distribution in a tissue section and then a serial section is robotically spotted
      with small volumes of trypsin solution to carry out in situ protease digestion.
      After hydrolysis, 2,5-Dihydroxybenzoic acid (DHB) matrix solution is applied to
      the digested spots, with subsequent analysis by IMS to reveal the spatial
      distribution of the various tryptic fragments. Sequence determination of the
      tryptic fragments is performed using on-tissue MALDI MS/MS analysis directly from
      the individual digest spots. This protocol enables protein identification
      directly from tissue while preserving the spatial integrity of the tissue sample.
      The procedure is demonstrated with the identification of several proteins in the
      coronal sections of a rat brain.

PMID- 17230434
TI  - Analysis of exacerbation rates in asthma and chronic obstructive pulmonary
      disease: example from the TRISTAN study.
AB  - Recurrent events in clinical trials have typically been analysed using either a
      multiple time-to-event method or a direct approach based on the distribution of
      the number of events. An area of application for these methods is exacerbation
      data from respiratory clinical trials. The different approaches to the analysis
      and the issues involved are illustrated for a large trial (n = 1465) in chronic
      obstructive pulmonary disease (COPD). For exacerbation rates, clinical interest
      centres on a direct comparison of rates for each treatment which favours the
      distribution-based analysis, rather than a time-to-event approach. Poisson
      regression has often been employed and has recently been recommended as the
      appropriate method of analysis for COPD exacerbations but the key assumptions
      often appear unreasonable for this analysis. By contrast use of a negative
      binomial model which corresponds to assuming a separate Poisson parameter for
      each subject offers a more appealing approach. Non-parametric methods avoid some
      of the assumptions required by these models, but do not provide appropriate
      estimates of treatment effects because of the discrete and bounded nature of the
      data.

PMID- 17230436
TI  - Statistics in public health policy. Proceedings of the Tenth Biennial CDC and
      ATSDR Symposium on Statistical Methods. Washington, DC, USA.

PMID- 17230435
TI  - Peer-support in coping with medical uncertainty: discussion of oophorectomy and
      hormone replacement therapy on a web-based message board.
AB  - The Facing Our Risk of Cancer Empowered (FORCE) website is devoted to women at
      risk for hereditary breast and ovarian cancers (HBOC). To understand the unique
      health concerns and emotional support needs of these women, we examined threads
      on the FORCE archived message boards with relevance to the broader HBOC
      community. We report on a thread discussing the controversial decision to use
      hormone replacement therapy (HRT) following prophylactic oophorectomy (PO). We
      used a qualitative research inductive process involving close reading, coding and
      identification of recurrent patterns, relationships and processes in the data.
      Twenty-nine women posted 177 messages over 7 months. Two main groups of women
      posted: (1) Women who were BRCA+, had completed PO, and were debating or
      adjusting their HRT options in terms of optimizing both quality and quantity of
      life. (2) Women who were BRCA+, were contemplating PO, but wanted to better
      understand the potential physical and psychological consequences of surgical
      menopause before deciding. Frustrated by physicians' lack of knowledge and
      contradictory media articles about the long-term consequences of HRT in BRCA+
      women, they sought resources, emotional support and specific experiential
      knowledge from each other and generated a unique sense of community and a high
      level of trust.

PMID- 17230437
TI  - Chemical and microphysical characterization of ambient aerosols with the aerodyne
      aerosol mass spectrometer.
AB  - The application of mass spectrometric techniques to the real-time measurement and
      characterization of aerosols represents a significant advance in the field of
      atmospheric science. This review focuses on the aerosol mass spectrometer (AMS),
      an instrument designed and developed at Aerodyne Research, Inc. (ARI) that is the
      most widely used thermal vaporization AMS. The AMS uses aerodynamic lens inlet
      technology together with thermal vaporization and electron-impact mass
      spectrometry to measure the real-time non-refractory (NR) chemical speciation and
      mass loading as a function of particle size of fine aerosol particles with
      aerodynamic diameters between approximately 50 and 1,000 nm. The original AMS
      utilizes a quadrupole mass spectrometer (Q) with electron impact (EI) ionization
      and produces ensemble average data of particle properties. Later versions employ
      time-of-flight (ToF) mass spectrometers and can produce full mass spectral data
      for single particles. This manuscript presents a detailed discussion of the
      strengths and limitations of the AMS measurement approach and reviews how the
      measurements are used to characterize particle properties. Results from selected
      laboratory experiments and field measurement campaigns are also presented to
      highlight the different applications of this instrument. Recent instrumental
      developments, such as the incorporation of softer ionization techniques (vacuum
      ultraviolet (VUV) photo-ionization, Li+ ion, and electron attachment) and high
      resolution ToF mass spectrometers, that yield more detailed information about the
      organic aerosol component are also described.

PMID- 17230438
TI  - Using hooves for high-resolution isotopic reconstruction of bovine dietary
      history.
AB  - The objective of this study was to ascertain whether sequential sampling and
      isotopic analysis of bovine hooves could be used to reconstruct the dietary
      history of cattle. A controlled, on-farm experiment was conducted in which cattle
      were switched from a barley-based diet to an isotopically different diet
      incorporating maize, urea and seaweed (the isotopic spacing between diets was
      13.6 per thousand for delta(13)C and 8.0 per thousand for delta(15)N) and
      maintained on that diet for 168 days. Postmortem sampling of the cleaned anterior
      wall of the lateral, left front claw was carried out on five individuals using a
      micro-drilling technique. From the first 60 mm of each claw, up to 41 samples
      with a spacing between them of less than 1 mm were collected. Bands were less
      than 1 mm deep and had a mean width of 1.2 mm. The hoof keratin showed a rapid
      increase followed by a slower increase in its delta(13)C and delta(15)N values
      following the diet switch, suggesting that C and N in hoof keratin originate from
      more than one pool. However, the response of the N isotope composition of the
      hoof was somewhat delayed compared with that of C. Estimated mean hoof growth
      rates for these cattle were 10.5 +/- 2.3 mm per month and 6.7 +/- 1.0 mm per
      month (+/-SD, n = 5) when receiving the barley-based transition diet and the
      maize-based experimental diet, respectively. These values are considerably higher
      than previous estimates obtained by visual methods and they suggest that diet may
      have a greater influence on hoof growth rates than seasonality. These results
      demonstrate that hooves are a suitable incremental tissue for high-resolution
      isotopic reconstruction of the dietary history of bovine animals.

PMID- 17230439
TI  - A tuberculosis vaccine based on phosphoantigens and fusion proteins induces
      distinct gammadelta and alphabeta T cell responses in primates.
AB  - Phosphoantigens are mycobacterial non-peptide antigens that might enhance the
      immunogenicity of current subunit candidate vaccines for tuberculosis. However,
      their testing requires monkeys, the only animal models suitable for gammadelta T
      cell responses to mycobacteria. Thus here, the immunogenicity of 6-kDa early
      secretory antigenic target-mycolyl transferase complex antigen 85B (ESAT-6-Ag85B)
      (H-1 hybrid) fusion protein associated or not to a synthetic phosphoantigen was
      compared by a prime-boost regimen of two groups of eight cynomolgus. Although
      phosphoantigen activated immediately a strong release of systemic Th1 cytokines
      (IL-2, IL-6, IFN-gamma, TNF-alpha), it further anergized blood gammadelta T
      lymphocytes selectively. By contrast, the hybrid H-1 induced only memory
      alphabeta T cell responses, regardless of phosphoantigen. These latter
      essentially comprised cytotoxic T lymphocytes specific for Ag85B (on average +
      430 cells/million PBMC) and few IFN-gamma-secreting cells (+ 40 cells/million
      PBMC, equally specific for ESAT-6 and for Ag85B). Hence, in macaques, a prime
      boost with the H-1/phosphoantigen subunit combination induces two waves of immune
      responses, successively by gammadelta T and alphabeta T lymphocytes.

PMID- 17230440
TI  - Antimicrobial peptides human beta-defensin (hBD)-3 and hBD-4 activate mast cells
      and increase skin vascular permeability.
AB  - Antimicrobial peptides human beta-defensins (hBD) are mainly produced by
      epithelia of several organs including skin, and participate in innate immunity by
      killing invading pathogens. Besides their microbicidal activities, hBD activate
      several inflammatory and immune cells. Since hBD are generated by tissues where
      mast cells are present, we hypothesized that these peptides could activate mast
      cells. In this study, we demonstrated that both hBD-3 and hBD-4 induced mast cell
      degranulation, prostaglandin D2 production, intracellular Ca2+ mobilization and
      chemotaxis. Furthermore, hBD-3- and hBD-4-induced activation of mast cells was
      suppressed by pertussis toxin and U-73122, inhibitors for G protein and
      phospholipase C, respectively. We further revealed that hBD-3 and hBD-4 increased
      vascular permeability in the skin, which was dependent on the presence of mast
      cells, because hBD-3 and hBD-4 failed to enhance vascular permeability in mast
      cell-deficient Ws/Ws rats. We also demonstrated that hBD-3 and hBD-4 induced
      phosphorylation of MAPK p38 and ERK1/2, which were further required for hBD
      mediated mast cell activation, as evidenced by the inhibitory effects of p38 and
      ERK1/2 inhibitors on mast cell degranulation. Together, these findings suggest
      the key role of hBD in inflammatory responses by recruiting and activating mast
      cells, and increasing vascular permeability.

PMID- 17230441
TI  - TREM-1 promotes survival during septic shock in mice.
AB  - Triggering receptor expressed on myeloid (TREM)-1 is integral to the inflammatory
      response occurring during septic shock, although its precise function has yet to
      be determined. Here we show that in vivo silencing of TREM-1 using siRNA duplexes
      in a fecal peritonitis mouse model resulted in a blunted inflammatory response
      and increased mortality. This was associated with impaired bacterial clearance
      related to marked inhibition of the neutrophil oxidative burst. By contrast, TREM
      1-silenced mice were highly resistant to a lethal endotoxin challenge, while
      partial silencing of TREM-1 in the bacterial peritonitis model produced a
      significant survival benefit. These data highlight the crucial role of the TREM-1
      pathway in mounting an adequate inflammatory and cytotoxic response to
      polymicrobial sepsis, and both the therapeutic promise and potential risks of its
      modulation.

PMID- 17230442
TI  - Dectin-1 promotes fungicidal activity of human neutrophils.
AB  - Human polymorphonuclear leukocytes (PMN) are a first line of defense against
      fungal infections. PMN express numerous pattern recognition receptors (PRR) that
      facilitate identification of invading microorganisms and ultimately promote
      resolution of disease. Dectin-1 (beta-glucan receptor) is a PRR expressed on
      several cell types and has been studied on monocytes and macrophages. However,
      the role played by dectin-1 in the recognition and killing of fungi by PMN is
      unknown. We investigated the ability of dectin-1 to mediate human PMN
      phagocytosis and fungicidal activity. Dectin-1 was expressed on the surface of
      PMN from all subjects tested (n=29) and in an intracellular compartment that co
      sedimented with azurophilic granules in Percoll density gradients. Soluble beta
      glucan and mAb GE2 (anti-dectin-1) inhibited binding and phagocytosis of zymosan
      by human PMN (e.g., ingestion was inhibited 40.1% by 30 min, p<0.001), and
      blocked reactive oxygen species production. Notably, soluble beta-glucan and GE2
      inhibited phagocytosis and killing of Candida albicans by PMN (inhibition of
      killing was 54.8% for beta-glucan and 36.2% for GE2, p<0.01). Our results reveal
      a mechanism whereby PMN dectin-1 plays a key role in the recognition and killing
      of fungal pathogens by the innate immune system.

PMID- 17230443
TI  - Combined single-clade candidate HIV-1 vaccines induce T cell responses limited by
      multiple forms of in vivo immune interference.
AB  - We assessed in mice whether broad CD8+ T cell responses capable of efficient
      recognition of multiple HIV-1 clades could be induced using current single-clade
      vaccine constructs that were or will be used in clinical trials in Europe and
      Africa. We found that single-clade A, B and C vaccines applied alone induced only
      limited cross-clade reactivity and that the epitope hierarchy varied according to
      the immunizing clade. However, combining single-clade HIV-1 vaccines into multi
      clade formulations resulted in multiple forms of in vivo immune interference such
      as original antigenic sin and antagonism, which dampened or even abrogated
      induction of responses to epitope variants and reduced the breadth of induced T
      cell responses. Simultaneous administration of individual clade-specific vaccines
      into anatomically separated sites on the body alleviated antagonism and increased
      the number of detectable epitope responses. Although cross-reactivity of murine
      CD8+ T cells does not directly translate to humans, the molecular interactions
      involved in triggering T cell responses are the same in mouse and man. Thus,
      these results have important ramifications for the design of both prophylactic
      and therapeutic vaccines against HIV-1 and other highly variable pathogens.

PMID- 17230444
TI  - Data protection in biomaterial banks for Parkinson's disease research: the model
      of GEPARD (Gene Bank Parkinson's Disease Germany).
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease.
      Although 10 gene loci have been identified to cause a Parkinsonian syndrome,
      these loci account only for a minority of PD patients. Large, systematic research
      programs are required to collect, store, and analyze DNA samples and clinical
      information to support further discovery of additional genetic components of PD
      or other movement disorders. Such programs facilitate research into the
      relationship between genotype and phenotype. The German Competence Network on
      Parkinson's disease (CNP) initiated the Gene Bank Parkinson's Disease Germany
      (GEPARD), providing an administrative and scientific infrastructure for the
      storage of DNA and clinical data that are electronically accessible and
      protective of patient rights. In this article, we offer guidance on how to
      establish a framework for a clinical genetic data and DNA bank, and describe
      GEPARD as a model that may be useful to other local, national, and international
      research groups developing similar programs.

PMID- 17230445
TI  - Protect from light: photodegradation and protein biologics.
AB  - The exposure of proteins to light and the ensuing chemical and physical
      degradation has been studied extensively for many years. The residues in proteins
      that undergo primary photooxidation include tryptophan, tyrosine, phenylalanine,
      and cysteine/cystine. While photooxidation has been recognized as a major
      contributor to protein degradation, the effects of photoinduced damage have not
      been widely studied for biopharmaceuticals. This is particularly important since
      photodegradation can lead to changes in primary, secondary, and tertiary
      structures of protein and these changes, while not definitively established,
      could lead to differences in long-term stability, bioactivity, or immunogenicity.
      In this review we briefly describe the major pathways of photodegradation for
      proteins followed by a description of the limited data on photodegradation of
      biopharmaceuticals and methods that have been used to reduce or prevent damage.
      It is our intent to spur additional research in this area for increasing the
      safety and effectiveness of biopharmaceutical products.

PMID- 17230446
TI  - ELAVL4, PARK10, and the Celts.
AB  - Genetic variability in ELAVL4 located in the PARK10 locus was recently associated
      with age-at-onset (AAO) in a series of Parkinson's disease (PD) patients
      originating from the United States. We examined five markers spanning ELAVL4 in
      Norwegian, United States, and Irish PD case-control samples. No association was
      found between the examined markers and AAO or PD in Norwegian or US samples.
      However, ELAVL4 markers (rs967582 and rs3902720) were significantly associated
      with susceptibility to PD in our Irish series. Our data suggest that the
      association between ELAVL4 and PD previously observed might be explained by a
      Celtic-founder effect.

PMID- 17230447
TI  - Asymmetrical alien hands in corticobasal degeneration.
AB  - There are several forms of alien limb, but alien limb in corticobasal
      degeneration (CBD) is not well understood. We studied a patient with CBD who
      demonstrated two different types of alien limb. With his right hand he
      demonstrated a tactile avoidance response with levitation. With his left hand, he
      demonstrated continuous tactile pursuit of the examiner's hand ("tactile
      mitgehen"). Mitgehen is often associated with frontal dysfunction, but avoidance
      response and levitation are often associated with parietal dysfunction.

PMID- 17230448
TI  - Regulation of PAI-1 gene expression during adipogenesis.
AB  - Obesity is characterized by elevated levels of circulating plasminogen activator
      inhibitor-1 (PAI-1), which contribute towards the development of secondary
      disorders such as type 2 diabetes mellitus and cardiovascular complications. This
      increase in plasma PAI-1 levels is attributed to an increase in PAI-1 derived
      from adipose tissue. This study shows that adipose tissue evolved into a major
      PAI-1 producing organ by gaining capacity during adipocyte differentiation to
      respond to inducers of PAI-1 transcription. This is mediated by a decrease in
      E2F1 protein levels, an increase in pRB levels and a decrease in pRB
      phosphorylation, all leading to a decrease in levels of free E2F, a known
      transcriptional repressor of PAI-1. Depletion of E2F1-3 was sufficient for
      inducers such as insulin to potently induce PAI-1 gene expression in pre
      adipocytes. Conversely, forced release of pRB-bound endogenous E2F using cell
      penetrating peptides can suppress PAI-1 gene expression in adipocytes. This study
      describes the novel paradigm of cellular differentiation-associated increase in
      PAI-1 gene expression which is mediated by a decrease in repressor activity, and
      describes a way of desensitising terminally differentiated cells to PAI-1
      inducing agents by restoring endogenous repressor activity.

PMID- 17230449
TI  - Simultaneous determination of lamotrigine, zonisamide, and carbamazepine in human
      plasma by high-performance liquid chromatography.
AB  - A high-performance liquid chromatography assay with ultraviolet detection was
      developed for the simultaneous determination of the anti-epileptic drugs
      lamotrigine, carbamazepine and zonisamide in human plasma and serum. Lamotrigine,
      carbamazepine, zonisamide and the internal standard chloramphenicol were
      extracted from serum or plasma using liquid-liquid extraction under alkaline
      conditions into an organic solvent. The method was linear in the range 1-30
      microg/mL for lamotrigine, 2-20 microg/mL for carbamazepine, and 1-40 microg/mL
      for zonisamide. Within- and between-run precision studies demonstrated
      coefficient of variation <10% at all tested concentrations. Other anti-epileptic
      medications tested did not interfere with the assay. The method is appropriate
      for determining lamotrigine, carbamazepine and zonisamide serum or plasma
      concentrations for therapeutic monitoring.

PMID- 17230450
TI  - Liquid chromatography-mass spectrometry method for the determination of
      venlafaxine in human plasma and application to a pharmacokinetic study.
AB  - A sensitive and selective liquid chromatographic-mass spectrometric (LC-MS)
      method for the determination of venlafaxine in human plasma has been developed.
      Samples were prepared using liquid-liquid extraction and analyzed on a C(18)
      column interfaced with a triple quadrupole mass spectrometer. Positive
      electrospray ionization was employed as the ionization source. The mobile phase
      was methanol-water containing 10 mmol/L ammonium acetate, pH 7.9 adjusted with
      aqueous ammonia (80:20, v/v) at the flow rate of 1.0 mL/min. The analyte and
      internal standard clozapine were both detected by use of selected ion monitoring
      mode. The method was linear in the concentration range of 1.0-200.0 ng/mL. The
      lower limit of quantification (LLOQ) was 1.0 ng/mL. The intra- and inter-day
      relative standard deviation across three validation runs over the entire
      concentration range was less than 10.1%. The accuracy determined at three
      concentrations (5.0, 50.0 and 150.0 ng/mL for venlafaxine) was within +/-10.0% in
      terms of relative error (RE). The method was successfully applied for the
      evaluation of pharmacokinetic profiles of venlafaxine capsule in 20 healthy
      volunteers. The results show AUC, T(max), C(max) and T(1/2) between the testing
      formulation and reference formulation have no significant difference (p > 0.05).
      Relative bioavailability was 103.4 +/- 14.1%.

PMID- 17230451
TI  - Chiral separation of three agrochemical toxins enantiomers by high-performance
      liquid chromatography on a vancomycin crystalline degradation products-chiral
      stationary phase.
AB  - This work aims to evaluate for the enantiomeric separations of three agrochemical
      toxins: haloxyfop-methyl, fenoxaprop-p-ethyl and indoxacarb on crystalline
      degradation products-chiral stationary phase (CDP-CSP) of high-performance liquid
      chromatography (HPLC) under normal and polar organic phases. In the normal phase,
      the mobile phase was n-hexane with alcohols including methanol and isopropanol as
      polar modifiers. In the polar organic phase mode, the mobile phase was methanol
      with different percentages of triethylammunium acetate. The influence of flow
      rate (0.3-0.9 mL/min), analyte concentration and silica gel particle sizes (10,
      15 and 30 microm) was investigated. This new chiral stationary phase showed
      excellent stereoselectivity for the two enantiomers of haloxyfop-methyl and
      fenoxaprop-p-ethyl and chiral recognition for indoxacarb under normal-phase mode.
      However, under polar organic phase, only indoxacarb was separated (alpha < 1.5).
      The chromatographic results were compared with commercial chiral columns.

PMID- 17230452
TI  - HPLC method for the determination and pharmacokinetic studies of four
      triterpenoids in rat plasma after oral administration of Ganoderma lucidum
      extract.
AB  - Four major triterpenoids (ganoderic acids C(2), B, K and H) in rat plasma after
      oral administration of G. lucidum extract were analyzed quantitatively by high
      performance liquid chromatography (HPLC). Plasma samples taken from rats were
      acidified with hydrochloric acid and extracted with dichloromethane-ethyl acetate
      (90:10). The chromatographic separation was achieved on an Agilent Zorbax SB
      C(18) column (250 x 4.6 mm, 5 microm) at 35 degrees C, with a linear gradient of
      acetonitrile and 0.03% aqueous phosphoric acid (v/v), at a flow rate of 1.0
      mL/min. The four triterpenoids and internal standard (hydrocortisone) were
      detected at a wavelength 252 nm. All calibration curves showed good linearity
      (r(2) > 0.99) within test ranges. The relative deviation of this method was less
      than 10% for intra- and inter-day assays, and the accuracy ranged from 89 to
      108%. The extract recovery for the four triterpenoids and internal standard
      ranged from 95 to 67%, and the QC samples were found to be stable according to
      the results of the stability study. This is the first report on determination of
      the major triterpenoids in rat plasma after oral administration of G. lucidum
      extract and the results provided a firm basis for clarifying the pharmacological
      effect of G. lucidum and evaluating the clinical applications of this medicinal
      fungus.

PMID- 17230453
TI  - Testosterone not associated with violent dreams or REM sleep behavior disorder in
      men with Parkinson's.
AB  - We examined the relationship between testosterone levels, violent dreams, and REM
      sleep behavior disorder (RBD) in 31 men with Parkinson's disease (PD): 12 with
      clinical RBD and 19 without. All PD patients with clinical RBD experienced
      violent dreams, but none of the 19 non-RBD patients reported violent dreams.
      While dream content appears to be more aggressive in PD patients with clinical
      RBD, the presence of violent dreams or clinical RBD is not associated with
      testosterone levels in men with PD.

PMID- 17230454
TI  - Use of survey and clinical data for screening and diagnosis.
AB  - BACKGROUND: U.S. prevalence of diabetes in 2005 was 20.8 million people (6.2
      million undiagnosed) (Diabetes Statistics. 2006). Recognizable preclinical stage
      is between 7 and 12 years. Efficient screening and early diagnosis can help: 1.
      avoid or delay development of diabetes. 2. treat early and avoid co-morbidities.
      DESIGN: Retrospective cross-sectional study of 153 113 adults ages 24 to 83 from
      the Behavioural Risk Factor Surveillance Systems (BRFSS)-2003 of whom 4379 had
      diabetes at their current age or during the previous year and 2190 adults ages 40
      to 74 from the National Health and Nutrition Examination Survey III, 211 of whom
      had glucose tolerance test result > or = 200 mg/dL. OBJECTIVES: To develop
      statistical models for screening and diagnosis. METHODS: Logistic and generalized
      linear and additive regression models, Akaike information criterion, area under
      the receiver operating characteristic (ROC) curve, Baye's rule. RESULTS: Area
      under the 'productivity' curve using BRFSS data is 0.65 indicating an average
      yield of 17.3 per cent. Survey data is useful also for diagnosis. Area under the
      ROC curve (AUC) using only survey data is 0.68. AUC for fasting plasma glucose
      (FPG) alone is 0.91. Stepwise drop one method of selecting co-variates for
      diagnosis included pre-test probability from BRFSS. When both FPG and pre-test
      information are included, AUC increases to 0.93. Reduction in residual deviance
      and 0.02 increase in AUC are statistically significant (p = 0.0012). Clinical
      significance of prior odds is shown by increase in accuracy and weighted average
      of sensitivity and specificity. Empirically estimated regression weights for pre
      test and test information vary with age and race and are not equal, as required
      by Baye's theorem. Overfitting index was less than 1 per cent. CONCLUSIONS: Cross
      section surveys are useful for increasing screening efficiency and diagnostic
      accuracy.

PMID- 17230455
TI  - Apolipoprotein E epsilon4 allele is associated with Parkinson disease risk in a
      Mexican Mestizo population.
AB  - We investigated the association between apolipoprotein E (APOE) alleles and
      genotypes and Parkinson disease (PD) in 229 unrelated Mexican Mestizo PD patients
      and 229 controls. Results showed that both APOE-epsilon4 allele and APOE
      epsilon4/epsilon3 genotype are associated with PD (OR = 1.736, P = 0.011; OR =
      1.688, P = 0.019, respectively). Mean age at onset of PD was not associated to
      any APOE allele or genotype, but was significantly earlier in familial PD when
      compared to sporadic cases (P = 0.025).

PMID- 17230456
TI  - In silico determination of intracellular glycosylation and phosphorylation sites
      in human selectins: implications for biological function.
AB  - Post-translational modifications provide the proteins with the possibility to
      perform functions in addition to those determined by their primary sequence.
      However, analysis of multifunctional protein structures in the environment of
      cells and body fluids is made especially difficult by the presence of other
      interacting proteins. Bioinformatics tools are therefore helpful to predict
      protein multifunctionality through the identification of serine and threonine
      residues wherein the hydroxyl group is likely to become modified by
      phosphorylation or glycosylation. Moreover, serines and threonines where both
      modifications are likely to occur can also be predicted (YinYang sites), to
      suggest further functional versatility. Structural modifications of hydroxyl
      groups of P-, E-, and L-selectins have been predicted and possible functions
      resulting from such modifications are proposed. Functional changes of the three
      selectins are based on the assumption that transitory and reversible protein
      modifications by phosphate and O-GlcNAc cause specific conformational changes and
      generate binding sites for other proteins. The computer-assisted prediction of
      glycosylation and phosphorylation sites in selectins should be helpful to assess
      the contribution of dynamic protein modifications in selectin-mediated
      inflammatory responses and cell-cell adhesion processes that are difficult to
      determine experimentally.

PMID- 17230457
TI  - Augmentation of restless legs syndrome with long-term tramadol treatment.
AB  - Restless legs syndrome (RLS) augmentation, defined as a kind of suppression of
      the circadian rhythm of the disease in which sensory and motor symptoms appear
      earlier during the day (and over previously unaffected body parts), with a
      progressive phase advance until, backwards, the symptoms may cover the entire
      day, has been described only after treatment with dopaminergic drugs. We report
      clinical and polysomnographic accounts of a patient developing RLS augmentation
      after long-term treatment with tramadol, an opioid agonist with selectivity for
      mu-receptor and added norepinephrine and serotonin reuptake inhibition
      properties. Polysomnographic measures showed an improvement of RLS and a
      disappearance of diurnal sensory and motor RLS symptoms after tramadol was
      stopped. Our case confirms a recent retrospective report of augmentation of RLS
      after treatment with tramadol, and begs the question whether augmentation is
      truly restricted to dopaminergic drugs.

PMID- 17230458
TI  - G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with
      multiple system atrophy.
AB  - Multiple system atrophy (MSA) is characterized clinically by Parkinsonism,
      cerebellar dysfunction, and autonomic impairment. Multiple mutations in the LRRK2
      gene are associated with parkinsonian disorders, and the most common one, the
      G2019S mutation, has been found in approximately 1% of sporadic cases of
      Parkinsonism. In a well-characterized cohort of 136 subjects with probable MSA
      and 110 neurologically evaluated control subjects, none carried the G2019S
      mutation. We conclude that the G2019S mutation in the LRRK2 gene is unlikely to
      be associated with MSA.

PMID- 17230459
TI  - Maternal protein restriction permanently programs adipocyte growth and
      development in adult male rat offspring.
AB  - We previously demonstrated that maternal protein restriction (MPR) during
      pregnancy and lactation led to fetal growth restriction and development of
      increased visceral adiposity in adult male rat offspring. Here we studied the
      rate of proliferation and differentiation of adipocyte precursors (preadipocytes)
      in vitro to investigate whether MPR may permanently program adipocyte growth and
      development in adult male offspring. Preadipocytes were isolated from visceral
      adipose tissue of control and MPR offspring at 130 days of age, and cultured
      under standard conditions. The rate of proliferation was studied by [(3)H]
      thymidine incorporation, and the rate of differentiation assessed with the use of
      biochemical and morphological markers. Although it did not affect the rate of
      differentiation, MPR increased the rate of preadipocyte proliferation by almost
      twofold. To ascertain if the increased proliferation was due to persisting in
      vivo influences or aberrations inherent in the precursor cells, we studied the
      rate of preadipocyte proliferation in subcultures. We found that the increased
      rate of proliferation of MPR preadipocytes persisted throughout the first two
      subcultures, indicative of an inherent abnormality. In addition, we examined the
      rate of preadipocyte proliferation under reduced serum conditions. We showed that
      MPR reduced the rate of preadipocyte proliferation to 56 and 35% of the control
      in the presence of 5 and 2.5% serum, respectively. Taken together, these results
      demonstrate that MPR permanently programs adipocyte growth and development such
      that adipocyte precursors derived from MPR offspring replicate excessively under
      standard culture conditions but exhibit markedly attenuated growth rate under
      reduced serum conditions.

PMID- 17230460
TI  - Large scale genetic screen identifies MAP17 as protein bypassing TNF-induced
      growth arrest.
AB  - Although activated macrophages destroy cancer cells more effectively than normal
      cells, the ability to escape activated macrophages is a characteristic of tumor
      cells. One of the mechanisms responsible for the specific killing of tumor cells
      by macrophages is the production of the cytokine tumor necrosis factor (TNF)
      alpha. Therefore, resistance to TNF may provide such cancer cells a selective
      advantage against host elimination. With the aim of identifying genes with these
      properties we undertook a large scale genetic screen to identify genes able to
      bypass TNF-induced G1 arrest. We identified MAP17, a small 17 kDa nonglycosylated
      membrane protein that localizes to the plasma membrane and the Golgi apparatus.
      Ectopic expression of MAP17 in tumor cells prevents TNF-induced G1 arrest by
      impairing p21waf1 induction. However, expression of MAP17 does not inhibit TNF
      induced apoptosis in Me180-sensitive tumor cells. The inhibition of TNF is
      specific since MAP17 does not alter the response to other cytokines such as
      IFNgamma. As described in the Xenopus oocyte system, MAP17 increases the uptake
      of mannose in some cells, but this effect is not responsible for TNF bypass. We
      have also analyzed the expression of MAP17 mRNA in a panel of cell lines. MAP17
      is expressed in 30% of cell lines of different origin. However, MAP17 mRNA
      expression did not correlate with TNF resistance. Our data indicates that
      although MAP17 expression might bypass TNF-induced growth arrest, it is not the
      only determinant of this response.

PMID- 17230461
TI  - Quantification of pseudoephedrine in human plasma by LC-MS/MS using mosapride as
      internal standard.
AB  - A simple, sensitive and rapid high-performance liquid chromatography/positive ion
      electrospray tandem mass spectrometry (LC-MS/MS) method was developed and
      validated for the quantification of pseudoephedrine in human plasma using
      mosapride as internal standard. Following solid-phase extraction, the analytes
      were separated using an isocratic mobile phase on a reverse-phase column and
      analyzed by MS/MS in the multiple-reaction monitoring mode using the respective
      [M + H](+) ions, m/z 166/148 for pseuoephedrine and m/z 422/198 for the IS. The
      method exhibited a linear dynamic range of 2-1000 ng/mL pseudoephedrine in human
      plasma. The lower limit of quantification was 2 ng/mL with a relative standard
      deviation of less than 9% for pseudoephedrine. Acceptable precision and accuracy
      were obtained for concentrations over the standard curve range. The total
      chromatographic run time of 2 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- 17230462
TI  - How to assess motor impairment in writer's cramp.
AB  - Writer's cramp is a task-specific hand dystonia affecting handwriting. Clinical
      scores such as the Arm Dystonia Disability Scale (ADDS) or Writer's Cramp Rating
      Scale (WCRS) as well as kinematic analysis of handwriting movements have been
      used to assess functional impairment in affected patients. In 21 patients with
      writer's cramp and healthy controls, we analyzed the kinematics of writing and
      cyclic drawing movements. We rated the severity of dystonia using the ADDS and
      WCRS and correlated the clinical scores with movement kinematics. Mean stroke
      frequency was significantly reduced in dystonic patients. Drawing movements
      showed more frequently a decrease in stroke frequency than handwriting movements.
      During circle drawing, mean vertical peak velocity was more variable in patients
      relative to controls, indicating an impaired ability to reproduce the same
      kinematic pattern over time. An increase in vertical writing pressure was only
      observed during handwriting but not during circle drawing and may reflect a
      compensatory effort to stabilize the pencil. Kinematic measures and individual
      ADDS and WCRS scores did not correlate with each other. The lack of correlation
      is not surprising as ADDS, WCRS, and kinematic analysis probe different aspects
      of motor impairment. The ADDS characterizes how dystonia affects a set of fine
      manual tasks, whereas the WCRS scores the manifestation of dystonia during
      handwriting. Therefore, the clinical scores and kinematic analysis of handwriting
      provide complementary insights into motor impairment. Future studies need to
      address which combination of clinical scores and kinematic measures are most
      appropriate to quantify impairment in writer's cramp.

PMID- 17230463
TI  - Structural white matter abnormalities in patients with idiopathic dystonia.
AB  - We investigated whether structural white matter abnormalities, in the form of
      disruption of axonal coherence and integrity as measured with diffusion tensor
      imaging (DTI), constitute an underlying pathological mechanism of idiopathic
      dystonia (ID), independent of genotype status. We studied seven subjects with ID:
      all had cervical dystonia as their main symptom (one patient also had spasmodic
      dysphonia and two patients had concurrent generalized dystonia, both DYT1
      negative). We compared DTI MR images of patients with 10 controls, evaluating
      differences in mean diffusivity (MD) and fractional anisotropy (FA). ID was
      associated with increased FA values in the thalamus and adjacent white matter,
      and in the white matter underlying the middle frontal gyrus. ID was also
      associated with increase in MD in adjacent white matter to the pallidum and
      putamen bilaterally, left caudate, and in subcortical hemispheric regions,
      including the postcentral gyrus. Abnormal FA and MD in patients with ID indicate
      that abnormal axonal coherence and integrity contribute to the pathophysiology of
      dystonia. These findings suggest that ID is not only a functional disorder, but
      also associated with structural brain changes. Impaired connectivity and
      disrupted flow of information may contribute to the impairment of motor planning
      and regulation in dystonia.

PMID- 17230464
TI  - Punding prevalence in Parkinson's disease.
AB  - The purpose of this study was to determine punding prevalence in an ambulatory
      Parkinson's disease (PD) population. We conducted a patient-and-caregiver
      completed punding survey in 373 consecutive patients in an academic ambulatory
      center. Completion rate was 78%. Only four patients were identified as punding.
      Patients did not retain insight to their behavior. Forty patients with high-dose
      levodopa monotherapy or levodopa and dopamine agonist treatment had physician
      administered interview. None had punding. Punding incidence was low in this
      patient group (1.4%) in contrast with previous reports of 14%. Despite the low
      incidence, this behavior is disruptive and should be carefully elicited by
      physicians caring for Parkinson's disease patients.

PMID- 17230465
TI  - Myoclonus-dystonia syndrome with severe depression is caused by an exon-skipping
      mutation in the epsilon-sarcoglycan gene.
AB  - We describe two affected individuals in a family with myoclonus-dystonia syndrome
      complicated with severe depression. One individual committed suicide. Molecular
      genetic analysis revealed a heterozygous point mutation in the epsilon
      sarcoglycan gene, which we show leads to skipping of exon 5. This report suggests
      that the psychiatric spectrum of MDS includes more severe depression.

PMID- 17230466
TI  - Selective diplopia in Parkinson's disease: a special subtype of visual
      hallucination?
AB  - Diplopia is sometimes reported by patients with Parkinson's disease (PD) without
      apparent oculomotor disorders. We assessed clinical features and associated
      oculomotor and perceptual performance in 14 patients (6 male, 8 female) with PD
      with a peculiar type of selective diplopia. Duplication of images was confined to
      single objects or persons, occurred repetitively, and lasted few seconds in all
      subjects. Frequency of episodes ranged from several episodes per day to three
      episodes per year. In six of seven subjects undergoing comprehensive
      ophtalmological examination, subtle ocular disorders (heterophoria, strabism,
      etc.) were found. Nine of 14 patients were suffering from current or previous
      visual hallucinations and 3 more patients developed hallucinations within 3 years
      of diplopia onset. Selective diplopia of isolated single objects and persons in
      PD is possibly related to hallucinosis and minor ocular disturbances seem to be a
      triggering factor for this peculiar type of misperception.

PMID- 17230467
TI  - The relationship between restless legs syndrome and neuropathy.

PMID- 17230468
TI  - Proteasome inhibitor model of Parkinson's disease in mice is confounded by
      neurotoxicity of the ethanol vehicle.
AB  - Defects in the ubiquitin-proteasome system have been implicated in Parkinson's
      Disease (PD). Recently, a rat model of PD was developed using a synthetic
      proteasome inhibitor (PSI), (Z-lle-Glu(OtBu)-Ala-Leu-al). We attempted to
      transfer this model to mouse studies, where genetics can be more readily
      investigated due to the availability of genetically modified mice. We treated
      C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 mul of
      70% ethanol over a 2-week-period. We found significant decreases in nigrostriatal
      dopamine in PSI-treated mice compared with saline-treated mice. However, we
      observed similar decreases in the ethanol-treated vehicle control group.
      Administration of ethanol alone led to significant long-term alterations in
      dopamine levels. Ethanol significantly eclipses the effects of PSI in the
      dopamine system, and therefore is a confounding vehicle for this model.

PMID- 17230469
TI  - Normal cardiovascular reflex testing in patients with parkin disease.
AB  - The objective of this study was to investigate cardiovascular autonomic function
      in patients with parkin disease. Ten patients with a genetically confirmed
      diagnosis were compared to 11 healthy controls. Symptoms related to autonomic
      dysfunction were collected by structured interviews. Cardiovascular autonomic
      reflex function was evaluated using a standard battery of eight tests. Autonomic
      tests included the study of sympathetic function through the analysis of blood
      pressure responses to head-up tilt, standing, isometric hand grip, cold pressor,
      mental arithmetic, Valsalva maneuver (Valsalva overshoot), and the study of
      parasympathetic function through the analysis of heart rate responses to deep
      breathing, hyperventilation, and Valsalva ratio. Seven out of 10 patients
      reported symptoms involving different aspects of autonomic function, while 5 out
      of 11 controls reported symptoms related exclusively to orthostatic dizziness and
      constipation. Symptoms related to bladder dysfunction were the most frequent
      autonomic abnormality occurring in six patients, followed by orthostatic
      dizziness and dry mouth (in four patients each). Constipation occurred in three
      patients, sialorrhea in two, and erectile dysfunction, dry eye, and warm
      intolerance in one each. Cardiovascular reflex testing revealed no difference
      between patients and controls in quantitative assessment of both sympathetic and
      parasympathetic functions, except for diastolic blood pressure after isometric
      hand grip that did not increase normally in parkin patients compared to controls
      (P = 0.007). These data show that cardiovascular dysautonomia is not associated
      to the parkin phenotype, whereas urinary complaints are more frequently reported
      by parkin patients than by controls. Urinary dysautonomia warrants further
      investigation in patients with parkin disease.

PMID- 17230470
TI  - Rat model of Parkinson's disease with bilateral motor abnormalities, reversible
      with levodopa, and dyskinesias.
AB  - Parkinson's disease (PD) is characterized by the bilateral degeneration of the
      midbrain dopamine-containing neurons with the most severe lesion in the
      posterolateral part of the substantia nigra pars compacta (SNpc). In humans, such
      lesions lead to specific motor abnormalities (i.e., akinesia, rigidity, and
      tremor) that are greatly improved by levodopa treatment. After a few years, the
      beneficial effect of the treatment is frequently offset by the development of
      dyskinesias. To improve treatment strategies, an animal model showing most of the
      histological and clinical characteristics of the human disease is mandatory. Ten
      rats received a bilateral injection of small doses of 6-OHDA in the medial
      forebrain bundle (MFB) and were compared with five sham-lesioned rats. The 6-OHDA
      lesioned rats progressively developed abnormal motor behavior (assessed by the
      stepping test) compared with the sham-lesioned rats. The lesioned rats greatly
      improved under levodopa treatment, but developed concomitant dyskinesias. All 6
      OHDA-lesioned animals had bilateral partial lesions of the SNpc, with the most
      severe lesion being in its posterolateral part. There was a significant
      correlation between the severity of the dopaminergic cell loss and the severity
      of the levodopa-induced dyskinesias. These rats constitute an interesting model
      of PD, sharing some of the main characteristics of the human disease.

PMID- 17230471
TI  - Validity of Hamilton Depression Inventory in Parkinson's disease.
AB  - Studies investigating the assessment of depression in Parkinson's disease (PD)
      are limited. We examined the concurrent validity and the internal consistency of
      the Hamilton Depression Inventory (HDI) and compared it to the Hamilton and
      Geriatric Depression Scales. PD patients (n = 79) were recruited from neurology
      clinics. Diagnosis of depressive disorder was made according to DSM-IV criteria.
      Receiver operating characteristic curves were used to calculate sensitivity,
      specificity, and positive and negative predictive values. The HDI exhibited an
      optimal cutoff for discriminating between depressed and nondepressed PD patients
      of 13.5/14.0 and is a valid instrument to use in the setting of PD.

PMID- 17230472
TI  - Impaired modulation of motor cortex excitability by homonymous and heteronymous
      muscle afferents in focal hand dystonia.
AB  - A decrease of heteronymous median nerve-evoked inhibition of corticospinal
      projections to forearm extensor muscles was reported in a group of 10 dystonic
      patients by Bertolasi and colleagues in 2003. Here we tested the excitability of
      corticomotoneuronal connections to both wrist extensor (ECR) and flexor (FCR)
      muscles after conditioning stimulation of median and also radial nerve at rest in
      a group of 25 patients with focal hand dystonia compared to 20 healthy subjects.
      We also investigated the effect of the wrist dystonic posture, either in flexion
      or in extension, on the afferent modulation of ECR and FCR motor evolved
      potentials (MEPs). The heteronymous (median-induced) but also homonymous (radial
      induced) inhibitions (interstimuli intervals 13-21 ms) of ECR MEP size observed
      in healthy subjects were decreased in patients. In addition, homonymous (median
      induced) facilitation of FCR MEP size was also decreased in patients while
      heteronymous inhibition (radial-induced) was not. Neither the involvement of the
      target muscle in the dystonic posture nor the origin of the afferent volley (from
      a dystonic muscle) influenced the degree of impairment of afferent modulation of
      the MEP. These findings support the view that a global abnormal somatosensory
      coupling in focal hand dystonia may contribute to an inadequate motor command to
      wrist muscles.

PMID- 17230473
TI  - Vitamin D and Parkinson's disease--a hypothesis.
AB  - Parkinson's disease (PD), a common disease of the elderly, is a movement disorder
      characterized by tremor, akinesia, and loss of postural reflexes, leading to
      immobility and frequent falls. It results from selective loss (death) of
      dopaminergic neurons in the substantia nigra region of the brain, largely
      developed prior to clinical diagnosis, and continuous after diagnosis, despite
      use of current therapeutic modalities. In PD in the United States the cause and
      mechanism of continued neuron cell death in the substantia nigra is currently
      unknown. We hypothesize, based upon several lines of evidence, that documented
      chronically inadequate vitamin D intake in the United States, particularly in the
      northern states and particularly in the elderly, is a significant factor in the
      pathogenesis of PD. This hypothesis implies that dietary aid for prevention and
      therapy for PD is possible.

PMID- 17230474
TI  - Fatal encephalitis in a patient with refractory celiac disease presenting with
      myorhythmia and carpal spasm.
AB  - We report the case of a woman with refractory celiac disease who developed
      abnormal spontaneous movements of the extremities and face consistent with
      myorhythmia. Investigation led to a diagnosis of encephalitis, confirmed by
      postmortem examination. The movements were likely caused by nonparaneoplastic
      encephalitis associated with refractory celiac disease. Etiologic and diagnostic
      considerations and treatment options are discussed.

PMID- 17230475
TI  - Diagnostic indicators of restless legs syndrome in primary care consultations:
      the DESYR study.
AB  - The objective of this study is to determine whether spontaneous complaints about
      sleep or the legs could be used as potential indicators of restless legs syndrome
      (RLS) in primary care. A total of 351 general practitioners participated in the
      study. In a first historical patient identification phase, all patients with
      spontaneous complaints of sleep or leg symptoms over the previous year were
      identified. A control group without such complaints was identified. In a second
      prospective data collection phase, those who consulted a participating physician
      were interviewed to assess consensus diagnostic criteria of RLS. Severity was
      assessed with the International Restless Legs Syndrome Study Group severity
      rating scale. Of 1,405,823 patients consulting during the historical phase, a leg
      complaint was reported in 61,685 and a sleep complaint in 40,568. A total of
      1,432 consulted during the prospective phase. A diagnosis of RLS was assigned to
      42.6% of patients with leg complaints, 35.5% of those with sleep complaints,
      54.9% of those with both complaints, and 12.9% of those with no complaints.
      Median RLS severity scores were 18.8 to 20.4. A total of 63.7% of patients were
      prescribed a venotonic, 43.7% a hypnotic, and 41.5% an anxiolytic. Complaints of
      sleep or leg symptoms are frequently associated with a diagnosis of RLS, and
      their presence should alert the physician to the possibility of a differential
      diagnosis of RLS.

PMID- 17230476
TI  - Pattern of subclinical pulmonary dysfunctions in Parkinson's disease and the
      effect of levodopa.
AB  - We performed a detailed evaluation of pulmonary function in 53 patients with
      idiopathic Parkinson's disease (PD) who did not have symptoms of pulmonary or
      cardiac dysfunction. There was a significant pulmonary dysfunction of restrictive
      type which partially responded to levodopa. Compared to men, women were more
      severely affected. Pulmonary function assessment is recommended in PD,
      irrespective of severity of disease.

PMID- 17230477
TI  - Accuracy of Medicare claims data in identifying Parkinsonism cases: comparison
      with the Medicare current beneficiary survey.
AB  - STUDY PURPOSE: Administrative databases are commonly used to examine use of
      healthcare service, with researchers relying on diagnostic codes to identify
      medical conditions. This study evaluates the accuracy of administrative claims in
      identifying Parkinsonism cases compared to the self-reported Parkinson's disease
      (PD). METHODS: The reference cases were identified based on the self-reported PD
      status and the use of PD drugs collected by the 1992-2000 Medicare Current
      Beneficiary Survey that contained 72,922 observations from 30,469 individuals.
      Using ICD-9 CM, cases with PD were extracted from the corresponding Medicare
      claims. We compared prevalence of PD obtained using different types of claims.
      RESULTS: The sensitivities were the highest when all claims were used (66%). All
      the specificities were greater than 99%. When drug use information was included
      in the gold standard, the sensitivities became lower, while the specificities and
      positive predictive values (PPVs) increased. Using more diagnostic codes improved
      the sensitivity of the identification process but reduced PPVs. CONCLUSIONS:
      Administrative claims can provide fairly accurate and practical approach to "rule
      in" patients with PD. Depending on the purpose of evaluation, researchers may
      consider using more categories of claims to improve the sensitivity of the
      identification algorithm or use fewer diagnoses to minimize number of false
      positive cases.

PMID- 17230478
TI  - Palatal tremor and orofacial stereotypies within the locked-in syndrome.

PMID- 17230479
TI  - Over 10 years of isolated autonomic failure preceding dementia and Parkinsonism
      in 2 patients with Lewy body disease.

PMID- 17230480
TI  - Endoscopic therapy of strictures in Crohn's disease.

PMID- 17230481
TI  - Association between parasite infection and immune responses in multiple
      sclerosis.
AB  - OBJECTIVE: To assess whether parasite infection is correlated with a reduced
      number of exacerbations and altered immune reactivity in multiple sclerosis (MS).
      METHODS: A prospective, double-cohort study was performed to assess the clinical
      course and radiological findings in 12 MS patients presenting associated
      eosinophilia. All patients presented parasitic infections with positive stool
      specimens. In all parasite-infected MS patients, the eosinophilia was not present
      during the 2 previous years. Eosinophil counts were monitored at 3- to 6-month
      intervals. When counts became elevated, patients were enrolled in the study.
      Interleukin (IL)-4, IL-10, IL-12, transforming growth factor (TGF)-beta, and
      interferon-gamma production by myelin basic protein-specific peripheral blood
      mononuclear cells were studied using enzyme-linked immunospot (ELISPOT). FoxP3
      and Smad7 expression were studied by reverse-transcriptase polymerase chain
      reaction. RESULTS: During a 4.6-year follow-up period, parasite-infected MS
      patients showed a significantly lower number of exacerbations, minimal variation
      in disability scores, as well as fewer magnetic resonance imaging changes when
      compared with uninfected MS patients. Furthermore, myelin basic protein-specific
      responses in peripheral blood showed a significant increase in IL-10 and TGF-beta
      and a decrease in IL-12 and interferon-gamma-secreting cells in infected MS
      patients compared with noninfected patients. Myelin basic protein-specific T
      cells cloned from infected subjects were characterized by the absence of IL-2 and
      IL-4 production, but high IL-10 and/or TGF-beta secretion, showing a cytokine
      profile similar to the T-cell subsets Tr1 and Th3. Moreover, cloning frequency of
      CD4+CD25+ FoxP3+ T cells was substantially increased in infected patients
      compared with uninfected MS subjects. Finally, Smad7 messenger RNA was not
      detected in T cells from infected MS patients secreting TGF-beta. INTERPRETATION:
      Increased production of IL-10 and TGF-beta, together with induction of CD25+CD4+
      FoxP3+ T cells, suggests that regulatory T cells induced during parasite
      infections can alter the course of MS.

PMID- 17230482
TI  - Hysterical chorea: Report of an outbreak and movie documentation by Arthur Van
      Gehuchten (1861-1914).
AB  - Psychogenic movement disorders remain a frequent and important clinical problem.
      First described in the Middle Ages, the dancing mania is considered to be one
      form of mass hysteria characterized by outbreaks of collective movement
      disorders. Patients may exhibit a wide variety of movement and gait disturbances,
      including tremulousness, jerks, or convulsions, usually with a sudden onset.
      Arthur Van Gehuchten (1861-1914), a distinguished Belgian neuroanatomist and
      neurologist, reported an outbreak of sudden involuntary movements in 13
      adolescent girls residing in an orphanage. The description is to be found in his
      book Les Maladies nerveuses, completed before 1914 and published posthumously in
      1920. The chapter is illustrated with sequential photographs of a girl exhibiting
      a peculiar gait, which is descriptively referred to as "choree salutatoire"
      (saluting chorea). The original film with these pictures has been retrieved and
      is presented here together with a very similar film excerpt also found in Van
      Gehuchten's film collection. Van Gehuchten's movie documentation of a psychogenic
      movement disorder--labeled chorea but which should probably be considered as
      dystonia according to contemporary classification--appears to be unique. This
      report illustrates the tremendous value of moving pictures in recording and
      analyzing movement disorders.

PMID- 17230483
TI  - Effects of unilateral subthalamic and pallidal deep brain stimulation on fine
      motor functions in Parkinson's disease.
AB  - Deep brain stimulation (DBS) is an effective treatment for selected patients with
      disabling Parkinson's disease (PD). The two main targets are the subthalamic
      nucleus (STN) and the globus pallidus internus (GPi), although it has not been
      established whether stimulation at one target is superior to the other. This
      prospective randomized study assessed the effects of unilateral DBS of the STN
      versus GPi on fine motor skills in 33 patients with advanced PD. Stimulation of
      either the STN (18 subjects) or GPi (15 subjects) in the off medication state
      significantly improved movement time and dexterity, but had little or no effect
      on reaction time. Overall, the extent of improvement did not differ between the
      two targets. The degree of improvement in movement time, but not dexterity, was
      correlated with the extent of preoperative medication responsiveness. Our
      findings suggest that DBS of the STN or GPi results in a similar improvement in
      hand movements at short-term follow-up. Preoperative medication responsiveness
      predicts improvement in some but not other motor tasks.

PMID- 17230484
TI  - Dopamine agonist-induced pathological gambling in restless legs syndrome due to
      multiple sclerosis.

PMID- 17230485
TI  - Reassessment of holoprosencephaly-diencephalic hamartoblastoma (HDH) association.
AB  - We report on a 23-week fetus with a hypothalamic hamartoma, lobar
      holoprosencephaly, right anophthalmia, and facial asymmetry, features which are
      consistent with the holoprosencephaly-diencephalic hamartoblastoma (HDH)
      association. In an attempt to better delineate HDH, we reviewed 19 published
      patients with similar features. The HDH clinical spectrum ranges from classic
      holoprosencephaly with micro/anophthalmia, multiple additional findings in non
      contiguous structures and early lethality, to isolated microforms of
      holoprosencephaly. Associated cephalic features mainly include cortical/neuronal
      migration defects (39%), meningeal anomalies (28%), brainstem/posterior fossa
      malformations (22%), dysmorphic ears (41%), facial asymmetry (35%), and
      hypoplastic mandible (29%). Fifty-three percent of patients have additional extra
      cephalic malformations, for example, vertebral/rib segmentation defects (50%),
      hypo/aplastic lungs (38%), congenital heart defect (29%), and urinary anomalies
      (29%). HDH shows etiological heterogeneity, that is, teratogenic exposure,
      chromosome imbalances, autosomal recessive as well as dominant "de novo"
      mutations. Several features could directly result from a disruptive sequence
      caused by an early hamartoma which alters the development of forebrain,
      hindbrain, meninges, and 1st-2nd branchial arches, although the pleiotropic
      action of genetic/environmental factors cannot be excluded. HDH does not emerge
      as a distinct syndrome, but other hypotheses, including separate conditions
      within a common pathway and the developmental field defect theory, are discussed.

PMID- 17230486
TI  - Severe hypertelorism, midface prominence, prominent/simple ears, severe myopia,
      borderline intelligence, and bone fragility in two brothers: new syndrome?
AB  - We report on two brothers, born to double first cousin Jordanian Arab parents,
      with a syndrome comprising severe hypertelorism with upslanted palpebral
      fissures, brachycephaly, abnormal ears, sloping shoulders, enamel hypoplasia, and
      osteopenia with repeated fractures. Both have severe myopia, mild to moderate
      sensori-neural hearing loss and borderline intelligence. Results of chromosome
      analysis were normal as was a FISH assay for subtelomeric rearrangements. The
      father has mild hypertelorism but the family history is otherwise unremarkable.
      We think that this represents a previously unrecognized autosomal or X-linked
      recessive syndrome.

PMID- 17230487
TI  - KBG syndrome: report of twins, neurological characteristics, and delineation of
      diagnostic criteria.
AB  - KBG syndrome is a multiple congenital anomaly (MCA) syndrome comprising
      developmental delay, postnatal short stature, and delayed bone age. Many physical
      anomalies involving the face, hands, and costovertebral axis have been described
      in this syndrome. We present twin males with KBG syndrome and a review of 50
      published case reports, with particular emphasis on the neurological aspects of
      KBG syndrome, including seizures, MRI findings, and behavior difficulties. It is
      argued that diagnostic criteria for KBG syndrome should include neurological
      involvement, that is, global developmental delay, seizures, and/or mental
      retardation (MR). The characteristic facial changes and representative hand and
      costovertebral anomalies are also defined. These diagnostic criteria were
      obtained from 50 publications and appeared to support the diagnosis in 43 cases.
      They will be helpful to pediatricians, geneticists, and neurologists in
      evaluating patients for this condition.

PMID- 17230488
TI  - Characterization of a 16 Mb interstitial chromosome 7q21 deletion by tiling path
      array CGH.
AB  - We report on a 42-year-old female patient with an interstitial 16 Mb deletion in
      7q21.1-21.3 and a balanced reciprocal translocation between chromosomes 6 and 7
      [karyotype 46,XX,t(6;7)(q23.3;q32.3)del(7)(q21.1q21.3)de novo]. We characterized
      the size and position of the deletion by tiling path array comparative genomic
      hybridization (CGH), and we mapped the translocation breakpoints on chromosomes 6
      and 7 by FISH. The clinical features of this patient-severe mental retardation,
      short stature, microcephaly and deafness-are in accordance with previously
      reported patients with 7q21 deletions. Chromosome band 7q21.3 harbors a locus for
      split hand/split foot malformation (SHFM1), and part of this locus, including the
      SHFM1 candidate genes SHFM1, DLX5, and DLX6, is deleted. The absence of limb
      abnormalities in this patient suggests either a location of the SHFM1 causing
      factor distal to this deletion, or reduced penetrance of haploinsufficiency of a
      SHFM1 factor within the deleted interval.

PMID- 17230489
TI  - De novo proximal duplication of 1(q12q22) in a female infant with multiple
      congenital anomalies.
AB  - Reports of small proximal 1q duplications are rare. We report a 1 month-old
      female who was referred to clinic because she was believed to have features
      suggestive of Turner syndrome. The patient's dysmorphic features included a
      prominent nose, low-set and crumpled ears, slightly high palate, short neck, high
      pitched cry, mild micrognathia, hypoplastic labia majora, and somewhat deep
      palmar creases. Traditional G-band chromosome studies of the patient were
      interpreted as 46,XX,dup(1)(q12q21). To further evaluate the extent of the
      chromosome 1 duplication, Spectral Karyotyping and a series of six fluorescence
      in situ hybridization (FISH) probes were utilized. The FISH probes refined the
      extent of the duplication to involve the region 1(q12q22) indicating the
      duplicated segment was larger than interpreted by the G-banding studies. This
      first case of non-mosaic proximal duplication of 1q to be characterized by
      multiple locus specific FISH probes should allow a more refined delineation of
      the phenotypic findings and clinical significance associated with this rare
      chromosomal duplication.

PMID- 17230490
TI  - Long-term follow-up of a 26-year-old male with duplication of 16p: clinical
      report and review.
AB  - We report on a 26-year-old male with profound psychomotor retardation and a
      pattern of dysmorphic features and malformations characteristic for duplication
      of the short arm of chromosome 16. He has an elongated face, sparse hair,
      upslanting palpebral fissures, anteverted nostrils, hypoplastic thumbs on both
      hands, and dislocation of several joints. His chromosome aberration was diagnosed
      at birth and was due to an unbalanced segregation of a maternal translocation
      t(2;16)(q36;p11). At 26 years of age he is, to the best of our knowledge, the
      oldest patient with duplication of 16p reported to date. We present a long-term
      observation of growth, psychomotor development, dysmorphic features and evolution
      of his skeletal and joint defects as well as a review of the literature.

PMID- 17230491
TI  - Duplication of 14q11.2 associates with short stature and mild mental retardation:
      a putative relation with quantitative trait loci.

PMID- 17230492
TI  - Maternal serum screening and 22q11.2 deletion syndrome.

PMID- 17230493
TI  - Development of gastroschisis: review of hypotheses, a novel hypothesis, and
      implications for research.
AB  - Gastroschisis, a ventral body wall defect, is a continuing challenge and concern
      to researchers, clinicians, and epidemiologists seeking to identify its cause(s)
      and pathogenesis. Concern has been renewed in recent years because, unlike most
      other birth defects, rates of gastroschisis are reportedly increasing in many
      developed and developing countries. No tenable explanation or specific causes
      have been identified for this trend. Rates of gastroschisis are particularly high
      among pregnancies of very young women. Such an intriguing association, not
      observed to this degree with other birth defects, may afford clues to the
      defect's cause. Understanding the causes of gastroschisis may provide insight to
      the defect's origin. In pursuing such causal studies, it would be helpful to
      understand the embryogenesis of gastroschisis. To date, four main embryologic
      hypotheses have been proposed: (1) Failure of mesoderm to form in the body wall;
      (2) Rupture of the amnion around the umbilical ring with subsequent herniation of
      bowel; (3) Abnormal involution of the right umbilical vein leading to weakening
      of the body wall and gut herniation; and (4) Disruption of the right vitelline
      (yolk sac) artery with subsequent body wall damage and gut herniation. Although
      based on embryological phenomena, these hypotheses do not provide an adequate
      explanation for how gastroschisis would occur. Therefore, we propose an
      alternative hypothesis, based on well described embryonic events. Specifically,
      we propose that abnormal folding of the body wall results in a ventral body wall
      defect through which the gut herniates, leading to the clinical presentation of
      gastroschisis. This hypothesis potentially explains the origin of gastroschisis
      as well as that of other developmental defects of the ventral wall.

PMID- 17230494
TI  - Effects of different immunosuppressive regimens on regulatory T-cells in
      noninflamed colon of liver transplant recipients.
AB  - BACKGROUND: Regulatory T-cells (Treg) are natural suppressors of autoimmunity.
      Previous studies indicate that immunosuppressive drugs, especially calcineurin
      inhibitors, may interfere with Treg homeostasis. Inflammatory bowel disease (IBD)
      can relapse or develop de novo after liver transplantation. IBD is associated
      with a relative deficiency of Treg. The aim of this study was to determine the
      effect of long-term immunosuppression on the presence of Treg in the noninflamed
      colonic mucosa of liver transplant recipients. METHODS: Colonic biopsies of
      normal mucosa of 36 liver transplant recipients on different types of
      immunosuppression and 11 controls were studied. Treg marker Foxp3 and Treg
      products transforming growth factor-beta (TGF-beta) and interleukin-10 (IL-10)
      were studied by quantitative polymerase chain reaction (Q-PCR) and
      immunohistochemistry. TGF-beta-induced Smad-protein 3 and 7 were studied by Q
      PCR. RESULTS: No significant differences between controls and patients were
      observed in IL-10, TGF-beta, and Smad expression. Mucosal Foxp3 mRNA levels and
      Foxp3+CD3+ cells were significantly reduced in transplant recipients using
      prednisone/azathioprine/tacrolimus compared with controls but no direct
      relationship between Foxp3 expression and 1 specific drug was detected.
      CONCLUSIONS: These results challenge the hypothesis that calcineurin-induced
      reduction of Treg or TGF-beta expression predisposes nontransplanted tissue to
      inflammation, but indicate that combined immunosuppression hampers Treg
      development in the intestine.

PMID- 17230495
TI  - Psychological treatment may reduce the need for healthcare in patients with
      Crohn's disease.
AB  - BACKGROUND: Few published studies examine the influence of psychological
      treatment on health care utilization in Crohn's disease. METHODS: The present
      substudy of a prospective, randomized, multicenter trial conducted in 69 of 488
      consecutive Crohn's disease (CD) patients was designed to investigate the way in
      which healthcare utilization is influenced by psychotherapy and relaxation in
      addition to standardized glucocorticoid therapy. Before and after a 1-year period
      of standardized somatic treatment the psychotherapy and control groups were
      compared with regard to hospital and sick-leave days. Predictors of healthcare
      utilization were analyzed. RESULTS: The comparison between groups before and
      after psychological treatment showed a significantly higher decrease of mean
      hospital days (P < 0.03) and sick-leave days in the treatment group compared with
      the controls. When a covariate analysis was applied to compare the data at
      randomization, the difference in hospital days remained statistically a trend (P
      < 0.1). Multivariate regression analysis detected a significant gender and
      depression effect for hospital days (cor r(2) = 0.114) and a significant gender
      and age effect for sick-leave days (cor r(2) = 0.112). CONCLUSION: A significant
      drop in healthcare utilization after psychological treatment demonstrates a clear
      benefit of this additional therapy. This is important, since the study failed to
      demonstrate significant changes in the psychosocial status or somatic course of
      study patients. Clinical and psychological factors influencing these outcomes are
      discussed.

PMID- 17230496
TI  - Expression of Gadd45a and p53 proteins in human pancreatic cancer: potential
      effects on clinical outcomes.
AB  - BACKGROUND AND OBJECTIVES: p53 gene has a dual role as a trigger of apoptosis and
      as an initiator of DNA repair. Gadd45a gene assumes the function to maintain the
      stability of genome. The present study was designed to assess the significance of
      Gadd45a and p53 protein expression on pancreatic cancer. METHODS: The expression
      of p53 and Gadd45a was immunohistochemically studied in 59 patients with
      pancreatic cancer. RESULTS: The positive expression rate of p53 and Gadd45a was
      67.8% and 42.4%, respectively. p53 expression in the patients <65 years was
      significantly higher than that in the patients >or=65 years (P=0.030). Gadd 45a
      expression showed no correlation to the patients' age. There was no relation for
      p53 expression to differentiation and TNM stages. Gadd 45a expression showed
      significant difference in histological differentiation (P=0.007). The median
      survival time of p53(+) and Gadd45a(+) group was shorter than that of p53(-) and
      Gadd45a(-) group (P>0.05), respectively. Meanwhile, the median survival time of
      p53 (+)Gadd45a(+) group was also shorter than that of p53(-)Gadd45a(-) group
      (P>0.05). CONCLUSIONS: p53 and Gadd45a proteins are both highly expressed in
      pancreatic cancer. The overexpression of p53 and Gadd45a may have connection with
      the malignant biologic behavior of pancreatic cancer.

PMID- 17230497
TI  - Alternative synthetic route to chiral N-substituted camphor-derived beta-amino
      alcohols.
AB  - An alternative route from (1R)-(+)-camphor to chiral N-substituted camphor
      derived beta-amino alcohol (4b-e) consists of four steps with a total yield of
      28%. N-Alkylation of camphor-derived beta-amino alcohol (4a) involves
      condensation and hydride reduction in one pot without isolation of intermediates.
      Condensation of 4a with aldehydes or ketones generates a mixture of 1,3
      oxazolidines (6) and imino-alcohols (7), which are reduced to 4b-e by NaBH(4).

PMID- 17230498
TI  - Pharmacokinetics of fexofenadine enantiomers in healthy subjects.
AB  - Fexofenadine, a substrate of P-glycoprotein and an organic anion transporter
      polypeptide, is commonly used to assess P-glycoprotein activity in vivo. The
      purpose of this study was to elucidate the pharmacokinetics of each fexofenadine
      enantiomer. After a single oral dose of racemic fexofenadine (60 mg), the plasma
      and urine concentrations of fexofenadine enantiomers were measured over the
      course of 24 h in six healthy subjects. The mean plasma concentration of R(+)
      fexofenadine was higher than that of S(-)-fexofenadine. The area under the plasma
      concentration-time curve (AUC(0-infinity)) and the maximum plasma concentration
      (C(max)) of R(+)-fexofenadine were significantly greater than those of the S(-)
      enantiomer (P = 0.0018 and 0.0028, respectively). The R/S ratios of AUC and
      C(max) of fexofenadine were 1.75 and 1.63, respectively. The oral clearance and
      renal clearance of S(-)-fexofenadine were significantly greater than that of R(+)
      fexofenadine (P = 0.0074 and 0.0036). On the other hand, the stereoselective
      metabolism of fexofenadine using recombinant CYP3A4 was investigated; however,
      fexofenadine enantiomers were not metabolized by CYP3A4. Fexofenadine is
      transported by both P-glycoprotein and OATP and is not metabolized by intestinal
      CYP3A. Our findings suggest that the affinity of P-glycoprotein for S(-)
      fexofenadine is greater than its affinity for the R(+)-enantiomer. Thus, P
      glycoprotein is likely to have chiral discriminatory abilities.

PMID- 17230499
TI  - Enantiomeric analysis of amino acids by using comprehensive two-dimensional gas
      chromatography.
AB  - The chiral separation of amino acids (AA) derivatised with ethyl chloroformate by
      using comprehensive two-dimensional gas chromatography is reported. A
      commercially available enantioselective capillary column (Chirasil-l-Val) has
      been tested as first-dimension column. Two nonenantioselective stationary phases
      (BPX50 and BP1) with different column lengths were combined with the
      enantioselective column, which represent chiral/polar and chiral/low-polarity
      column sets, respectively. These column sets were evaluated to determine the most
      useful column combination to provide improved separation efficiency of
      enantioselective AA analysis. Separations of AA mixtures derivatised either as
      their N-trifluoroacetyl methyl esters or with methyl chloroformate, performed on
      a chiral/low-polarity column set, are also shown. The method was demonstrated for
      chiral analysis of AAs in different beer samples. The major AA in the beer
      samples was proline with amounts ranging from around 65-95% with minor contents
      of glycine and the l-enantiomers of alanine, valine, leucine, and isoleucine.
      Small amounts of d-alanine, at about 1, 1.5, and 15% were detected in the three
      samples.

PMID- 17230500
TI  - Enhanced efficiency due to the use of achiral additives in the optical resolution
      of 1-phenylethylamine by its glutaric acid derivative.
AB  - Racemic 1-phenylethylamine was optically resolved by its own derivative formed
      with glutaric acid namely (+)-(R)-N-(1-phenylethyl)glutaramic acid. The amide
      acid resolving agent was synthesized from (+)-(R)-1-phenylethylamine by N
      derivatization. The glutaric acid derivative was the next in a homologous series
      of dicarboxilic acid derivatized resolving agents of racemic 1-phenylethylamine.
      Resolution results obtained with the oxalic, malonic, and succinic acid
      derivatives were previously discussed(1). Each of the above derivative resolving
      agents could be successfully applied as resolving agents of 1-phenylethylamine.
      The efficiency of the present optical resolution using (+)-(R)-N-(1
      phenylethyl)glutaramic acid resolving agent was remarkably inferior to the
      results obtained by its shorter chained homologues(1). Use of achiral additives,
      like urea, thiourea, N-methylurea, and N,N'-dimethylurea caused large increase in
      the efficiency of the resolution by (+)-(R)-N-(1-phenylethyl)glutaramic acid
      resolving agent. Precipitated salts obtained in the resolutions performed in the
      presence of the additives were investigated by thermoanalysis, X-ray powder
      diffraction, and optical microscopy. Based on the analytical data, the
      improvement of the resolution results was attributed to the influence of the
      additives on the crystal nucleation processes of the diasteromeric salts.

PMID- 17230501
TI  - Family-based and case-control studies reveal no association of lipocalin-type
      prostaglandin D2 synthase with schizophrenia.
AB  - Several observations point to the involvement of disturbed lipid biology in
      schizophrenia. Reduced response to niacin flushing test, which involves
      vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences,
      together with decreased CSF levels of lipocalin-type prostaglandin D2 synthase
      (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since
      PTGDS is also a carrier for lipophilic molecules such as retinoids and thyroid
      hormones, altered PTGDS levels might influence both PGD2-mediated signaling, and
      vitamin A and thyroid hormone availability. To test whether genetic variants of
      PTGDS are involved in the etiology of schizophrenia, we searched for variants in
      the coding and regulatory regions of the gene. We identified four previously
      described polymorphisms. Using two case-control samples from Portugal and Brazil,
      none of the polymorphisms tested was associated with the disease. In addition, no
      transmission distortion was observed in an independent parents-offspring sample
      from the Azorean Islands. Our data do not support the involvement of the PTGDS
      gene in the etiology of schizophrenia.

PMID- 17230502
TI  - Multiple histone deacetylases repress tumor suppressor gene ARHI in breast
      cancer.
AB  - ARHI is a maternally imprinted tumor suppressor gene that is expressed in normal
      breast and ovarian epithelial cells but not in most breast and ovarian cancers.
      Our earlier studies showed that histone deacetylases (HDACs) in complexes with
      transcription factors E2F1 and E2F4 play an important role in downregulating ARHI
      expression in breast cancer cells. To determine which HDAC or HDACs are
      responsible for repressing ARHI, we cotransfected vectors expressing HDACs 1-11
      with an ARHI/luciferase reporter into SKBr3 and MCF-7 breast cancer cells.
      Expression of multiple HDACs consistently reduced ARHI promoter activity in a
      dose-dependent manner. We also found that the expression level of HDACs 1-3 was
      higher in breast cancer cell lines than in normal breast epithelial cells. In
      agreement with their repressive function, depletion of HDACs 1, 3 and 11 not only
      significantly increased the ARHI promoter activity of the transfected reporter
      but also activated the transcription of the endogenous ARHI gene. Furthermore,
      depletion or inhibition of HDACs by small interfering RNA of HDAC11 or by
      trichostatin A, respectively, increased E2F acetylation. Chromatin
      immunoprecipitation assays revealed that HDACs 1 and 3 are bound to the ARHI
      promoter. Taken together, our results suggest that the activity of multiple HDACs
      contributes to the repression of the ARHI tumor suppressor gene in breast cancer
      cells. Since HDAC inhibitors are now being used to treat breast cancer, the
      reactivation of ARHI in these cancer cells may serve as a new biomarker with
      which to monitor the treatment effects.

PMID- 17230503
TI  - Variability in the clinical phenotype among families with HNPCC--the potential
      importance of the location of the mutation in the gene.

PMID- 17230504
TI  - Antitumor activity of ALK1 in pancreatic carcinoma cells.
AB  - In this study, the authors investigated the expression of activin receptor-like
      kinase 1 (ALK1) in pancreatic carcinoma and evaluated its potential role as a
      tumor suppressor in vitro and in vivo. Endogenous ALK1 expression was
      demonstrated by immunohistochemistry in both pancreatic tumor tissue and
      peritumoral normal tissue from 6 patients and by RT-PCR in 8/12 established
      pancreatic cancer cell lines. Ectopic expression of a constitutively active (ca)
      ALK1 mutant in TGF-beta sensitive PANC-1 and COLO-357 cells augmented
      transcriptional activation of a Smad2/3 responsive reporter, and slowed down
      basal growth in vitro. Both effects were further enhanced by TGF-beta/ALK5
      stimulation, suggesting largely independent nuclear Smad signaling by both type I
      receptors. Upon orthotopic transplantation of PANC-1-caALK1 into immunodeficient
      mice, tumor size was strongly reduced and was associated with a lower microvessel
      density in the PANC-1-caALK1-derived tumors. In vitro, this mutant efficiently
      blocked TGF-beta-induced epithelial-to-mesenchymal transdifferentiation and
      suppressed TGF-beta/ALK5-mediated activation of the p38 MAPK pathway.
      Mechanistically, caALK1 silenced MyD118, an immediate TGF-beta target gene whose
      protein product, GADD45beta, couples Smad signaling to p38 activation. These
      results show that ALK1 activation in pancreatic tumor cells is antioncogenic by
      inducing ALK5-independent growth inhibition and by blocking TGF-beta/ALK5
      mediated epithelial-to-mesenchymal transdifferentiation and, possibly, invasion
      and metastatic progression.

PMID- 17230505
TI  - Does high-dose carmustine increase overall survival in supratentorial high-grade
      malignant glioma? An EBMT retrospective study.
AB  - Radiotherapy plus concomitant and adjuvant temozolomide have demonstrated
      improved survival for glioblastoma. However, prognosis remains poor. High-doses
      chemotherapy with carmustine is another way to improve response and survival by
      increasing the dose delivered. Myelotoxicity imposes autologous stem cell rescue.
      European Group for Blood and Marrow Transplantation experience of this treatment
      in patients with high-grade glioma was reported here. A retrospective analysis of
      217 patients from European Group for Blood and Marrow Transplantation database
      was realized. Ninety-six patients underwent complete surgical resection while the
      121 others had partial resection or only biopsy and were evaluable for an
      antitumor effect. Patients received 800 mg/m2 of carmustine intravenously at
      least 1 month after neurosurgery. Forty-eight to 72 hr after chemotherapy, 108
      patients received autologous hematopoietic stem cells from bone marrow harvest
      and 109 patients autologous hematopoietic stem cells from peripheral blood.
      Radiotherapy was started approximately 40 days after transplantation. Ten deaths
      were related to the treatment. Of the 121 patients evaluable for tumor response,
      64 (53%) presented an objective response. This protocol appear feasible, but with
      toxicity-related mortality of 4.5%. Median overall survival was 20 months and
      median time to treatment failure was 7 months. Overall survival and time to
      treatment were correlated with age, quality of resection and histological
      subtypes. In glioblastoma multiforme, age and surgery quality appeared to be
      prognostic factors. Compared with Stupp et al.'s recent study, this study did not
      favor high-dose carmustine for patients with glioblastoma multiforme with
      complete surgical resection.

PMID- 17230506
TI  - Mammalian target of rapamycin is activated in human gastric cancer and serves as
      a target for therapy in an experimental model.
AB  - The mammalian target of rapamycin (mTOR) has become an interesting target for
      cancer therapy through its influence on oncogenic signals, which involve
      phosphatidylinositol-3-kinase and hypoxia-inducible factor-1alpha (HIF-1alpha).
      Since mTOR is an upstream regulator of HIF-1alpha, a key mediator of gastric
      cancer growth and angiogenesis, we investigated mTOR activation in human gastric
      adenocarcinoma specimens and determined whether rapamycin could inhibit gastric
      cancer growth in mice. Expression of phospho-mTOR was assessed by
      immunohistochemical analyses of human tissues. For in vitro studies, human
      gastric cancer cell lines were used to determine S6K1, 4E-BP-1 and HIF-1alpha
      activation and cancer cell motility upon rapamycin treatment. Effects of
      rapamycin on tumor growth and angiogenesis in vivo were assessed in both a
      subcutaneous tumor model and in an experimental model with orthotopically grown
      tumors. Mice received either rapamycin (0.5 mg/kg/day or 1.5 mg/kg/day) or
      diluent per intra-peritoneal injections. In addition, antiangiogenic effects were
      monitored in vivo using a dorsal-skin-fold chamber model. Immunohistochemical
      analyses showed strong expression of phospho-mTOR in 60% of intestinal- and 64%
      of diffuse-type human gastric adenocarcinomas. In vitro, rapamycin-treatment
      effectively blocked S6K1, 4E-BP-1 and HIF-1alpha activation, and significantly
      impaired tumor cell migration. In vivo, rapamycin-treatment led to significant
      inhibition of subcutaneous tumor growth, decreased CD31-positive vessel area and
      reduced tumor cell proliferation. Similar significant results were obtained in an
      orthotopic model of gastric cancer. In the dorsal-skin-fold chamber model,
      rapamycin-treatment significantly inhibited tumor vascularization in vivo. In
      conclusion, mTOR is frequently activated in human gastric cancer and represents a
      promising new molecular target for therapy.

PMID- 17230507
TI  - Simultaneous blockade of VEGFR-1 and VEGFR-2 activation is necessary to
      efficiently inhibit experimental melanoma growth and metastasis formation.
AB  - Metastasis continues to be the major cause of morbidity and mortality in
      malignant melanoma. In our study, we explored whether inhibition of VEGFR-1 or
      VEGFR-2 signaling conveys distinct suppressive effects on B16 melanoma
      subcutaneous growth and metastasis formation. The inhibition of VEGFR-1 or -2
      alone had no significant influence on both melanoma growth and metastasis
      formation. In contrast, simultaneous blockade of VEGFR-1 and -2 signaling
      strongly suppressed progression in both B16 tumor models. There was no expression
      of VEGFR-1 or -2 detectable on the B16 cells used, excluding the melanoma cells
      as direct therapeutic targets. Analyzing the contribution of progenitor-like
      cells during melanoma metastasis formation, we observed an enhanced proliferation
      and mobilization of VEGFR-1+ myeloid and VEGFR-2+ endothelial cells with
      progenitor potential by the induction of melanoma lung metastasis, which was not
      influenced by interference with VEGFR signaling. These results indicate that the
      antimetastatic effects exerted by combined inhibition of VEGFR-1 and -2 signaling
      were mediated via targeting cell populations other than progenitors only. Sole
      inhibition of VEGFR-1 signaling led to a strong reduction of the CD45-positive
      inflammatory infiltrate in the tumor tissue. However, the formation of lung
      metastasis was not affected, indicating that inhibition of the inflammatory
      response was not sufficient to efficiently block B16 melanoma metastasis
      development. Taken together, our data suggest that in the utilized B16 tumor
      models the blockade of both the inflammatory and the VEGFR-2-dependent angiogenic
      response are necessary to effectively inhibit solid tumor growth and formation of
      lung metastasis by B16 melanoma cells.

PMID- 17230508
TI  - Silibinin synergizes with mitoxantrone to inhibit cell growth and induce
      apoptosis in human prostate cancer cells.
AB  - The purpose of these experiments was to assess the synergistic activity of
      silibinin with chemotherapy agents in clinical use against prostate cancer.
      Silybin-phytosome, a commercially available formulation containing silibinin, has
      recently been studied in a phase I clinical trial. The silibinin doses used in
      the present study are clinically achievable based on the preliminary phase I
      data. DU145, PC-3 and LNCaP prostate cancer cells were seeded in 96-well plates
      in triplicate. Twenty-four hours later, silibinin (10, 20 and 40 microM) and
      either mitoxantrone or docetaxel were added to the designated wells. Seventy-two
      hours post-treatment, cell viability was determined with a tetrazolium-based
      assay. The combination index (CI) for determination of a synergistic effect was
      calculated, with values of <0.9 indicating synergy and values >1.1 antagonism.
      Apoptosis was also assessed using a luminescent assay after 72 hr of treatment
      with media alone, silibinin, mitoxantrone, or silibinin plus mitoxantrone.
      Silibinin showed a synergistic effect with mitoxantrone, as measured by reduction
      in cell viability. The CI values ranged from 0.413 to 2.650 for the combination
      of silibinin and mitoxantrone; in contrast, treatment with docetaxel and
      silibinin showed little or no synergy, with CI values of 0.898-4.469. In
      concordance with these findings, the addition of silibinin increased the level of
      apoptosis compared to mitoxantrone alone, particularly in the PC-3 cells. The
      combination of silibinin and mitoxantrone exhibits a pattern of synergy in
      reducing cell viability with increased apoptosis. These data are important in the
      planning of future clinical applications of silibinin.

PMID- 17230509
TI  - Less aggressive treatment and worse overall survival in cancer patients with
      diabetes: a large population based analysis.
AB  - The purpose of this study was to document the prevalence of diabetes among newly
      diagnosed cancer patients and to evaluate the influence of diabetes on stage at
      diagnosis, treatment and overall survival. We performed a population-based
      analyses of all 58,498 cancer patients newly diagnosed between 1995 and 2002 in
      the registration area of the Eindhoven Cancer Registry. Stage of cancer, cancer
      treatment and comorbidities were actively collected by hospital medical records
      review. Follow-up of all patients was completed until January 1, 2005. Nine
      percent of all cancer patients had diabetes at the time of cancer diagnosis. The
      prevalence of diabetes was highest among patients with cancer of the pancreas
      (19%), uterus (14%) and among young men with kidney cancer (8%). Colon, breast
      and ovarian cancer patients with diabetes were more often diagnosed with a higher
      tumour stage (p < 0.05). Patients with diabetes and cancer of the oesophagus,
      colon, breast and ovary were treated less aggressively compared to those without
      diabetes (p < 0.05). During the follow-up period 3,902 of 5,555 cancer patients
      with diabetes died and 29,909 of 52,943 cancer patients without diabetes died.
      For all cancers combined, in a multivariate cox-regression model, adjusting for
      age, gender, stage, treatment and cardiovascular disease, patients with diabetes
      experienced a significant increase in overall mortality (HR = 1.44, 95% CI 1.40
      1.49), ranging however from 0 to 40% for different types of cancer, compared to
      those without diabetes. In conclusion, diabetic cancer patients frequently were
      treated less aggressively and had a worse prognosis compared to those without
      diabetes.

PMID- 17230510
TI  - Evidence for heritable predisposition to epigenetic silencing of MLH1.
AB  - Epigenetic silencing of MLH1 is the most common cause of defective DNA mismatch
      repair in endometrial and colorectal cancers. We hypothesized that variation in
      the MLH1 gene might contribute to the risk for MLH1 methylation and epigenetic
      silencing. We undertook a case-control study to test for the association between
      MLH1 variants and abnormal MLH1 methylation. Eight MLH1 SNPs were typed in the
      normal DNA from women with endometrial carcinoma. For these studies, the cases
      were women whose cancers exhibited MLH1 methylation (N = 98) and the controls
      were women whose cancers had no MLH1 methylation (N = 219). One MLH1 SNP,
      rs1800734, located in the MLH1 CpG island at -93 from the translation start site,
      was significantly associated with MLH1 methylation as were age at diagnosis and
      patient body mass index. In validation experiments, a similar-sized cohort of
      colorectal carcinoma patients (N = 387) showed a similar degree of association
      with the -93 SNP; a smaller cohort of endometrial carcinomas (N = 181) showed no
      association. Combining all 3 cohorts showed an odds ratio of 1.61 (95% CI: 1.20
      2.16) for the AA or AG vs. GG genotype at the -93 SNP. Identification of risk
      alleles for MLH1 methylation could shed light on mechanisms of epigenetic
      silencing and may ultimately lead to new approaches to the prevention or
      treatment of malignancies associated with MLH1 inactivation.

PMID- 17230511
TI  - The use of histone deacetylase inhibitor FK228 and DNA hypomethylation agent 5
      azacytidine in human bladder cancer therapy.
AB  - The long-term disease-free survival in patients with metastatic transitional cell
      carcinoma (TCC) is still considerably low. Novel chemotherapeutic agents are
      needed to decrease the morbidity and mortality of TCC. In this study, we have
      evaluated several epigenetic modifiers for their therapeutic application in
      bladder cancer. Both histone deacetylase inhibitors (FK228, TSA) and DNA
      hypomethylating agent (5-Azacytidine) were tested using in vitro assays such as
      cell viability, cell cycle analysis and western blot to determine their
      mechanisms of action. Drug combination experiments were also designed to study
      any additive or synergistic effects of these agents. In addition, two bladder
      cancer xenograft models (one subcutaneous and one orthotopic) were employed to
      assess the therapeutic efficacy of these agents in vivo. Three agents exhibited
      various growth inhibitory effects on 5 different TCC cell lines in a dose- and
      time-dependent manner. In addition to G2/M cell cycle arrest, FK228 is more
      potent in inducting apoptosis than the two other single agents, and combination
      of both FK228 and 5-Aza further enhances this effect. p21 induction is closely
      associated with FK228 or TSA but not 5-Aza, which is mediated via p53-independent
      pathway. Consistent with in vitro results, FK228 exhibited a significant in vivo
      growth inhibition of TCC tumor in both subcutaneous and orthotopic xenograft
      models. FK228 is a potent chemotherapeutic agent for TCC in vivo with minimal
      undesirable side effects. The elevated p21 level mediated via p53 independent
      pathway is a hallmark of FK228 mechanism of action.

PMID- 17230512
TI  - Impact of disseminated tumor cells in bone marrow at diagnosis in patients with
      nonmetastatic prostate cancer treated by definitive radiotherapy.
AB  - The purpose of this study was to explore whether detection of disseminated tumor
      cells (DTCs) in bone marrow (BM) of nonmetastatic prostate cancer (PC) was
      associated with other clinical or histopathological factors at diagnoses or
      clinical outcome subsequent to definitive radiotherapy (RT). We evaluated BM
      aspirates from 272 cT(1-4)pN(0)M(0) PC patients by immunocytochemistry employing
      anticytokeratin antibodies (AE1/AE3). BM-status was compared with clinical and
      histopathological parameters. Long-term clinical outcome was assessed in 131 of
      the patients who all had completed definitive RT with or without androgen
      deprivation (AD), initiating treatment >5 years before cut-off date June 1, 2005.
      They had at least 1 unfavorable prognostic feature defined as cT(3-4) or Gleason
      score (GS) >or= 7B or PSA >or= 10 microg/l. Overall death, cause-specific death,
      distant metastases (DM) as first clinical relapse, local failure as first
      clinical relapse and biochemical failure were defined as end-points. DTCs were
      detected in 18% of the patients and were associated with increasing GS (p = 0.04)
      and percentage of Gleason pattern 4/5 (p = 0.04). The 7-year cumulative risk of
      DM was 21% for BM-positive patients vs. 6% for BM-negative patients (p = 0.07).
      In patients receiving RT without AD (n = 75), the 7-year cumulative risk of DM
      for BM-positive patients was 28% vs. 9% for BM-negative patients (p = 0.03). BM
      status did not have impact on other end-points. In conclusion our study shows
      that presence of DTCs in BM at diagnosis was associated with the histological
      differentiation of the primary tumor and an increased risk of developing distant
      metastases after RT.

PMID- 17230513
TI  - Inhibition of heat shock protein-90 modulates multiple functions required for
      survival of human T-cell leukemia virus type I-infected T-cell lines and adult T
      cell leukemia cells.
AB  - The molecular chaperone Hsp90 is involved in the stabilization and conformational
      maturation of many signaling proteins that are deregulated in cancers. The
      geldanamycin derivative 17-AAG is currently tested in clinical trials and known
      to inhibit the function of Hsp90 and promote the proteasomal degradation of its
      misfolded client proteins. ATL is a fatal malignancy of T lymphocytes caused by
      HTLV-I infection and remains incurable. Since Hsp90 is overexpressed in HTLV-I
      infected T-cell lines and primary ATL cells, we analyzed the effects of 17-AAG on
      cell survival, apoptosis and expression of signal transduction proteins. HTLV-I
      infected T-cell lines and primary ATL cells were significantly more sensitive to
      17-AAG in cell survival assays than normal PBMCs. 17-AAG induced the inhibition
      of cell cycle and apoptosis. These effects could be mediated by inactivation of
      NF-kappaB, AP-1 and PI3K/Akt pathways, as well as reduction of expression of
      proteins involved in the G1-S cell cycle transition and apoptosis. Proteasome
      inhibition interfered with 17-AAG-mediated signaling proteins depletion.
      Collectively, our results indicate that 17-AAG suppresses ATL cell survival
      through, at least in part, destabilization of several client proteins and suggest
      that 17-AAG is a potentially useful chemotherapeutic agent for ATL.

PMID- 17230514
TI  - Clinical significance of sperm protein 17 expression and immunogenicity in
      esophageal cancer.
AB  - We recently identified sperm protein 17 (Sp17) transcripts in esophageal squamous
      cell carcinomas (ESCCs) by differential display. This study was designed to
      determine the clinical significance of Sp17 protein in different stages of
      esophageal tumorigenesis and to test the hypothesis that aberrant localization of
      Sp17 protein to immunosurveillant site may lead to production of anti-Sp17
      antibodies in serum, which may be of clinical relevance in ESCCs. Sp17
      transcripts were detected by RT-PCR in 26 of 30 (86%) ESCCs, while no transcripts
      were detected in normal esophageal tissues. Rabbit polyclonal antibody was raised
      against an immunogenic peptide of Sp17 and used to evaluate protein expression by
      immunohistochemistry. Expression of Sp17 protein was observed in 60/80 (75%) of
      ESCCs and 27/30 (90%) dysplastic tissues, while no detectable Sp17 expression was
      observed in 13 distant histologically normal epithelia. Sixteen of the 60
      immunopositive ESCCs showed nuclear expression in addition to cytoplasmic
      localization of the protein. The circulating levels of anti-Sp17 antibodies,
      determined by ELISA, were significantly elevated in ESCC patients when compared
      with normal subjects (p < 0.001). Increasing Sp17 antibody titers were observed
      to be associated with the progressive disease in 4 patients. In conclusion, the
      study demonstrates expression of Sp17 protein in esophageal tumor as well as
      dysplastic tissues, suggesting it to be an early event in the development of
      ESCC. To our knowledge, this is the first report showing elevated levels of anti
      Sp17 antibodies in ESCC patients.

PMID- 17230515
TI  - HAS1 expression in bladder cancer and its relation to urinary HA test.
AB  - Hyaluronic acid (HA) levels are elevated in bladder cancer tissues and regulate
      tumor growth and progression. Urinary HA levels measured by the HA test are an
      accurate marker for bladder cancer. In cells, HA is synthesized by one of the 3
      HA-synthase(s) i.e., HAS1, HAS2 and HAS3. In this study, we examined HAS1
      expression in bladder cancer cells and tissues. Real-time RT-PCR and northern
      blot analyses showed that HAS1 transcript levels are elevated 5- to 10-fold in
      bladder cancer tissues, when compared with normal tissues (p < 0.001). Among the
      3 HAS1 splice variants, only HAS1-va was expressed in bladder tissues, but the
      expression was significantly lower than the wild type HAS1 transcript. Increased
      HAS1 expression in bladder tumor tissues correlated with increased tissue HA
      levels (p < 0.001). Size of the large HA species (2.0 x 10(6) D) present in
      bladder tissues was consistent with the size of the HA polymer synthesized by
      HAS1. The amount of HA produced by bladder cancer cell lines correlated with the
      expression of HAS1 protein. Immunohistochemical analyses of bladder tumor tissues
      showed that HAS1 and HA expression had 79-88% sensitivity and 83.3-100%
      specificity. Both HAS1 and HA expression in bladder cancer tissues correlated
      with a positive HA urine test (p < 0.001). HAS1 expression correlated with tumor
      recurrence, prior treatment (p < 0.05) and possibly disease progression (p =
      0.058). Therefore, elevated HAS1 expression in bladder tumor tissues contributes
      to a positive HA urine test and may have some prognostic potential.

PMID- 17230516
TI  - Enhancing dendritic cell vaccine potency by combining a BAK/BAX siRNA-mediated
      antiapoptotic strategy to prolong dendritic cell life with an intracellular
      strategy to target antigen to lysosomal compartments.
AB  - Dendritic cell (DC)-based vaccines have become important in immunotherapeutics as
      a measure for generating antitumor immune responses. We have previously
      demonstrated that linkage of the antigen gene to a lysosomal targeting signal, a
      sorting signal of the lysosome-associated membrane protein type 1 (LAMP-1),
      enhances the potency of DC-based vaccines. DCs have a limited life span,
      hindering their long-term ability to prime antigen-specific T cells. In this
      study, we attempted to further improve the potency of a DC vaccine that targets
      human papilloma virus 16 (HPV16) E7 to a lysosomal compartment (DC-Sig/E7/LAMP-1)
      by combining a strategy to prolong DC life. We show that small interfering RNA
      targeting Bak and Bax proteins can be used to allow transfected DCs to resist
      being killed by T cells. This is done by downregulating these proapoptotic
      proteins, which have been known as so-called gate keepers in mitochondria
      mediated apoptosis. DCs expressing intact E7 or Sig/E7/LAMP-1 became resistant to
      attack by CD8+ T cells after transfection with BAK/BAX siRNA, leading to enhanced
      E7-specific T cell activation in vitro and in vivo. More importantly, vaccination
      with E7-presenting DCs transfected with BAK/BAX siRNA generated a strong
      therapeutic effect against an E7-expressing tumor in vaccinated mice, compared
      with DCs transfected with control siRNA. Our data indicate that a combination of
      strategies to enhance intracellular Ag processing and to prolong DC life may
      offer a promising strategy for improving DC vaccine potency.

PMID- 17230517
TI  - Inhibitors of histone deacetylases as potential therapeutic tools for high-risk
      embryonal tumors of the nervous system of childhood.
AB  - The origin of malignant embryonal tumors is incompletely understood and certain
      risk groups remain difficult to treat. The epigenetic structure of DNA and its
      lesions play a role in the origin of these neoplasms. Manipulation of the
      epigenome may offer novel treatment options. The authors evaluated the
      cytotoxicity of histone deacetylase inhibitors (HDI) [MS-275, SAHA, TSA, M344,
      M360, D85, SW55, SW187 and valproic acid (VPA)] on 13 embryonal tumor cell lines
      [4 medulloblastomas, 5 neuroblastomas, 2 atypical teratoid/rhabdoid tumors
      (AT/RT), and 2 malignant rhabdoid tumors of the kidney (RTK)] in MTT assay. In
      addition, HDI effects on hyperacetylation, reexpression of growth regulatory
      genes and apoptosis were characterized by Western analysis, RT-PCR and annexin-V
      staining. All HDI inhibited cell proliferation in a time- and dose-dependent
      manner. VPA was least cytotoxic with GI50 values after 72 hr ranging from 53.6 to
      332.9 microM, while TSA was most efficient with GI50 values after 72 hr ranging
      from 0.01 to 8.8 microM. M344 and M360 were also highly effective. Western blot
      revealed hyperacetylation of histone H4 after HDI treatment. Reactivation of
      several genes including the proapoptotic CASP8 was identified by RT-PCR. Annexin
      V staining demonstrated a dose and time dependent induction of apoptosis. HDI
      inhibited the growth of medulloblastoma, neuroblastoma and rhabdoid tumors in
      vitro. Treatment with HDI induced the reactivation of growth regulatory genes and
      consequently apoptosis. Our results warrant further studies and may help in the
      design of new protocols geared at the treatment of high risk embryonal tumors.

PMID- 17230518
TI  - Anatomical subsite discrepancy in relation to the impact of the consumption of
      alcohol, tobacco and betel quid on esophageal cancer.
AB  - The carcinogenetic impact of risk factors on esophageal cancer (EC) may differ
      according to the portion of the esophagus where the tumor occurs. It is unclear
      why more esophageal squamous cell carcinomas (SCC) developed in the middle
      location. We carried out a multicenter case-control study in Taiwan to assess
      anatomical subsite risk discrepancy for this neoplasm in regard to the
      consumption of alcohol, tobacco and betel quid. Four hundred forty seven incident
      patients with pathology-proven SCC of the esophagus (107 were upper-third [U/3
      EC], 199 middle-third [M/3-EC] and 141 lower-third [L/3-EC] cases), as well as
      1,022 gender, age and study hospital matched controls were analyzed by unordered
      polytomous logistic regression. All consumption of the three substances was
      related to the development of each subsite of EC, with a heterogeneously higher
      risk for current smokers (adjusted odds ratio (AOR) = 6.2) found in M/3-EC and
      for current chewers, in U/3-EC (AOR = 4.9). The joint risk of contracting lower
      two-third EC for drinking and smoking appeared to significantly surpass those
      estimated by a multiplicative interaction model. Concomitant exposure to these
      two agents brought the risks of EC at all three subsites up to 10- to 23.9-fold
      and additional tobacco-free betel quid to a 30.3- to 75.0-fold. In conclusion,
      tumor subsite discrepancy risk is related to prolonged exposure to tobacco and
      betel quid with inflorescence. Alcohol interacts with tobacco in a stronger supra
      multiplicative way in the middle portion of the esophagus, probably explaining
      why esophageal SCC occurs more commonly at this anatomical location.

PMID- 17230520
TI  - Differential involvement of reactive oxygen species in apoptosis induced by two
      classes of selenium compounds in human prostate cancer cells.
AB  - Selenium is a promising chemopreventive agent for prostate cancer, possibly via
      an induction of apoptosis. Earlier studies have shown that selenite induces DNA
      single strand breaks (SSBs), reactive oxygen species (ROS), p53 Ser-15
      phosphorylation and caspase-dependent and -independent apoptosis, whereas a
      methylselenol precursor methylseleninic acid (MSeA) induces caspase-mediated
      apoptosis regardless of p53 status. Here we address three main questions: What
      types of ROS are induced by selenite vs. MSeA in LNCaP (p53 wild type, androgen
      responsive) and DU145 (mutant p53, androgen-independent) prostate cancer cells?
      Does ROS generation depend on androgen signaling? What are the relationships
      among ROS, DNA SSBs, p53 and caspases? We show that selenite (5 microM) induced
      superoxide and hydrogen peroxide in LNCaP cells much more than in DU145 cells and
      the ROS generation was not affected by physiological androgen stimulation. MSeA
      (10 microM) induced apoptosis without either type of ROS in both cell lines. In
      LNCaP cells, we established superoxide as a primary mediator for selenite-induced
      DNA SSBs, p53 activation and caspase-mediated apoptosis. Furthermore a p53
      dominant negative mutant attenuated selenite-induced ROS, leading to a
      proportionate protection against apoptosis. The results support the p53
      mitochondria axis in a feedback loop for sustaining superoxide production to lead
      to efficient caspase-mediated apoptosis by selenite. In contrast, caspase
      mediated apoptosis induced by MSeA does not involve ROS induction. Since p53 is
      frequently mutated or deleted in prostate cancer and many other cancers, our
      results suggest that genotoxic vs. nongenotoxic classes of selenium may exert
      differential apoptosis efficacy depending on the p53 status of the cancer cells.

PMID- 17230521
TI  - Anti-apoptotic role of TWIST and its association with Akt pathway in mediating
      taxol resistance in nasopharyngeal carcinoma cells.
AB  - TWIST, a basic helix-loop-helix transcription factor, has been reported to be
      associated with development and progression of human cancer. Recently, over
      expression of TWIST is found in cancer patients with shorter survival and poor
      response to chemotherapy. Previously, we found that upregulation of TWIST was
      responsible for the development of acquired resistance to taxol in a
      nasopharyngeal carcinoma (NPC) cell line, HNE1-T3 (Wang et al., Oncogene,
      2004;24:274). In this study, we investigated the underlying molecular mechanisms
      responsible for the TWIST-mediated taxol resistance. By comparison of the
      parental HNE1 and its derivative HNE1-T3 cell lines, we found that the resistance
      to taxol in HNE1-T3 cells was associated with suppression of taxol-induced
      apoptosis evidenced by decreased expression of Bak and Bax and increased Bcl-2,
      as well as inhibition of PARP and caspase cleavage and DNA ladder formation.
      However, there was no correlation between taxol sensitivity and alterations on
      G2/M cell cycle distribution, suggesting that the TWIST-induced taxol resistance
      is mediated through protection against apoptosis but not mitotic arrest. Analysis
      of additional 8 NPC cell lines showed that upregulation of TWIST was associated
      with resistance to microtubule disrupting agents, especially taxol, and
      inactivation of TWIST through small RNA interference led to increased sensitivity
      to taxol-induced cell death. Subsequent studies also demonstrated that the TWIST
      mediated taxol resistance may be regulated through its positive involvement with
      the Akt pathway. Our findings suggest an underlying molecular mechanism
      responsible for the TWIST-mediated chemodrug resistance and suggest a target for
      overcoming taxol resistance in cancer cells.

PMID- 17230523
TI  - Mobile phone use and risk of glioma in 5 North European countries.
AB  - Public concern has been expressed about the possible adverse health effects of
      mobile telephones, mainly related to intracranial tumors. We conducted a
      population-based case-control study to investigate the relationship between
      mobile phone use and risk of glioma among 1,522 glioma patients and 3,301
      controls. We found no evidence of increased risk of glioma related to regular
      mobile phone use (odds ratio, OR = 0.78, 95% confidence interval, CI: 0.68,
      0.91). No significant association was found across categories with duration of
      use, years since first use, cumulative number of calls or cumulative hours of
      use. When the linear trend was examined, the OR for cumulative hours of mobile
      phone use was 1.006 (1.002, 1.010) per 100 hr, but no such relationship was found
      for the years of use or the number of calls. We found no increased risks when
      analogue and digital phones were analyzed separately. For more than 10 years of
      mobile phone use reported on the side of the head where the tumor was located, an
      increased OR of borderline statistical significance (OR = 1.39, 95% CI 1.01,
      1.92, p trend 0.04) was found, whereas similar use on the opposite side of the
      head resulted in an OR of 0.98 (95% CI 0.71, 1.37). Although our results overall
      do not indicate an increased risk of glioma in relation to mobile phone use, the
      possible risk in the most heavily exposed part of the brain with long-term use
      needs to be explored further before firm conclusions can be drawn.

PMID- 17230522
TI  - Apomine, an inhibitor of HMG-CoA-reductase, promotes apoptosis of myeloma cells
      in vitro and is associated with a modulation of myeloma in vivo.
AB  - Apomine, a novel 1,1 bisphosphonate ester, increases the rate of degradation of
      HMG-CoA reductase, inhibiting the mevalonate pathway and thereby blocking
      cholesterol biosynthesis. We have investigated whether Apomine can induce myeloma
      cell apoptosis in vitro and modulate myeloma disease in vivo. Apomine induced a
      dose-dependent increase in apoptosis in NCI H929, RPMI 8226 and JJN-3 human
      myeloma cells. Apomine, unlike the bisphosphonate, alendronate, had no measurable
      effect on osteoclastic bone resorption in vitro. To investigate the effect of
      Apomine in vivo, 5T2MM murine myeloma cells were injected into C57BL/KaLwRij
      mice. After 8 weeks all animals had a serum paraprotein and were treated with
      Apomine (200 mg/kg), or vehicle, for 4 weeks. Animals injected with 5T2MM cells
      and treated with vehicle developed osteolytic bone lesions, reduced cancellous
      bone area, decreased bone mineral density (BMD) and increased osteoclast number.
      Apomine caused a decrease in serum paraprotein and a decrease in tumor burden.
      Apomine inhibited the development of osteolytic lesions and prevented the tumor
      induced decreases in BMD. Apomine had no effect on osteoclast number in contrast
      to what had been seen previously with the bisphosphonate, zoledronic acid,
      suggesting that these are direct effects of Apomine on myeloma cells. This
      demonstrates that Apomine is able to promote myeloma cell apoptosis in vitro and
      inhibit the development of multiple myeloma and lytic bone disease in vivo. The
      use of bisphosphonate esters such as Apomine represents a novel therapeutic
      approach in the treatment of myeloma and, indirectly, the associated bone
      disease.

PMID- 17230524
TI  - Isolation of two regions on rat chromosomes 5 and 18 affecting mammary cancer
      susceptibility.
AB  - We previously mapped several quantitative trait loci (QTLs) controlling DMBA
      induced mammary tumor development in female rats derived from a SPRD-Cu3
      (susceptible strain) x WKY (resistant strain) cross. Two of these QTLs were
      assigned to chromosomes 5 and 18. In the present study, we generated and
      characterized congenic strains in which a segment of WKY chromosomes 5 or 18 was
      introduced in the SPRD-Cu3 genetic background, thereby physically demonstrating
      that each of these two chromosomes controls mammary tumor multiplicity. The
      chromosome 5 QTL (Mcstm1) accounts for 7 tumors per animal (versus a total of 11
      tumors per SPRD-Cu3 rat). The chromosome 18 QTL (Mcstm2) accounts for 3 tumors
      per animal and is the first chemically-induced mammary cancer susceptibility
      locus assigned to this chromosome. In addition, the Mcstm1 region was shown to
      also controls tumor latency. These loci thus play a major role in chemically
      induced mammary tumor development. QTLs controlling chemically-induced or
      estrogen-induced mammary tumor development have independently been identified on
      chromosomes 5 and 18, using susceptible strains others than SPRD-Cu3. Therefore
      the haplotype structure of the relevant chromosome regions was analyzed in the
      different strains. Some chromosome regions were found to be highly mosaic
      (haplotype blocks < 1 Mb), while one region showed an apparently conserved
      haplotype block of 7.5 Mb. This analysis points to limited regions that could
      harbor the causative genes and also indicates that at least Mcstm2 is a novel
      QTL.

PMID- 17230525
TI  - High grade cervical lesions are caused preferentially by non-European variants of
      HPVs 16 and 18.
AB  - The intratypic variability of HPVs 16 and 18 has been extensively studied and has
      been used as an important tool in epidemiological studies of viral transmission,
      persistence and progression to clinically relevant cervical lesions. Infections
      by non-European variants of HPVs 16 and 18 are associated with an increased risk
      for the development of high grade squamous intraepithelial lesions (HSIL). Our
      aim was to correlate the intratypic molecular variability of both HPV types and
      risk of persistent infection and lesion outcome in a cohort study conducted in
      Brazil. We characterized molecular variants of HPV types 16 and 18 by sequencing
      a fragment of the LCR, and of the E6 and L1 genes, for HPV-16 variants only. For
      both types, European variants composed the most prevalent and diverse group.
      Persistent infections with HPV-18 were associated with continuous detection of
      European variants. However, risk for simultaneous detection of HSIL and HPV DNA
      was higher in women harboring non-European variants of HPV-16. The same trend was
      observed with HSIL detected during follow-up. Our study confirms the association
      between non-European variants and risk of cervical neoplasia, and highlights the
      importance of their geographic distribution for cervical cancer risk assessment.

PMID- 17230526
TI  - Effects of base excision repair gene polymorphisms on pancreatic cancer survival.
AB  - To explore the association between single nucleotide polymorphisms of DNA repair
      genes and overall survival of patients with pancreatic cancer, we conducted a
      study in 378 cases of pancreatic adenocarcinoma who were treated at The
      University of Texas M. D. Anderson Cancer Center between February 1999 and
      October 2004 and were followed up to April 2006. Genotypes were determined using
      genomic DNA and the MassCode method. Overall survival was analyzed using the
      Kaplan-Meier plot, log-rank test and Cox regression. We observed a strong effect
      of the POLB A165G and T2133C genotypes on overall survival. The median survival
      time (MST) was 35.7 months for patients carrying at least 1 of the 2 homozygous
      variant POLB GG or CC genotypes, compared with 14.8 months for those carrying the
      AA/AG or TT/TC genotypes (p = 0.02, log rank test). The homozygous variants of
      hOGG1 G2657A, APEX1 D148E and XRCC1 R194W polymorphisms all showed a weak but
      significant effect on overall survival as demonstrated by either log rank test or
      multivariate COX regression after adjusting for other potential confounders. In
      combined genotype analysis, a predominant effect of the POLB homozygous variants
      on survival was observed. When POLB was not included in the model, a slightly
      better survival was observed among those carrying none of the adverse genotypes
      than those carrying at least one of the adverse genotypes. These observations
      suggest that polymorphisms of base excision repair genes significantly affect the
      clinical outcome of patients with pancreatic cancer. These observations need to
      be confirmed in a larger study of homogenous patient population.

PMID- 17230527
TI  - Expression of a novel alternatively spliced variant of NADP(H)-dependent retinol
      dehydrogenase/reductase with deletion of exon 3 in cervical squamous carcinoma.
AB  - NADP(H)-dependent retinol dehydrogenase/reductase (NRDR) plays an important role
      in maintaining the homeostasis of retinoid. Aberrations in retinoid metabolism
      are considered as early events in carcinogenesis. We identified a novel
      alternatively spliced variant, NRDRB1, in HeLa cell and human cervical squamous
      carcinoma tissues, which is characterized by a complete deletion of exon 3. The
      latter resulted in changes in subcellular localization of NRDRB1 when compared
      with the peroxisomal localization of NRDR. To clarify the clinical significance
      of NRDRB1, we investigated its mRNA and protein expressions in normal cervical
      and cervical squamous carcinoma tissues, using RT-PCR, quantitative real-time
      PCR, Gateway expressing system, immunoprecipitation, immunoblotting, MALDI-TOF
      mass spectrometry and immunohistochemistry. We detected NRDRB1 mRNA in 14 of 26
      (53.9%) cervical cancer tissues, but in none of the 12 normal cervical tissues.
      NRDRB1 protein was expressed in NRDRB1 mRNA-positive cases. While the full-length
      NRDR mRNA was observed in both normal and neoplastic cervical tissues, its
      protein was only expressed in normal cervical epithelium. The results presented
      here provide evidence that metabolic disturbances of retinal and retinoic acid,
      due to abnormal splicing and functional disorder of NRDR, may be involved in
      cervical tumorigenesis.

PMID- 17230529
TI  - Somatic mutations at the trinucleotide repeats of androgen receptor gene in male
      hepatocellular carcinoma.
AB  - Androgen and androgen receptor (AR) have long been implicated in liver
      carcinogenesis, especially for the male dominance feature. However, whether AR
      gene could occur in somatic mutations that might contribute to this process has
      not yet been studied. DNA sequencing and genotyping were conducted for detecting
      the genetic aberrations of AR gene in 257 primary hepatocellular carcinomas
      (HCCs) and also the dysplastic nodules (DN) from another 11 patients. Twenty-one
      AR somatic mutations causing amino acid changes were identified in HCC and even
      in the precancerous DN. The missense somatic mutations of AR were rare in HCC (2
      cases) but the trinucleotide repeat (TNR) changes, both at (CAG)n and (GGC)n, was
      a more common one (19 cases). Notably, all these mutations occurred in male
      patients and most TNR changes belonged to the contraction type (15 out of 19
      cases, 78.9%), which has been reported to associate with increased AR
      transcriptional activity. Most samples with TNR changes did not show
      microsatellite instability, suggesting a different cause for these TNR mutations.
      Although no significant correlation was identified between AR mutations and the
      clinicopathologic parameters, we found the (CAG)n length significantly shorter in
      hepatitis B virus (HBV)(+) HCCs than in HBV(-) HCCs and the (GGC)n length
      significantly correlates with the overall survival. In conclusion, the mis-sense
      somatic mutations of AR were rare in HCC but the TNR change was a more common
      one, which exclusively occurred in males. Moreover, the length of TNR carried
      clinical significance in special HCC group.

PMID- 17230528
TI  - Nutritional factors in relation to endometrial cancer: a report from a population
      based case-control study in Shanghai, China.
AB  - We evaluated the role of dietary nutrients in the etiology of endometrial cancer
      in a population-based case-control study of 1,204 newly diagnosed endometrial
      cancer cases and 1,212 age frequency-matched controls. Information on usual
      dietary habits was collected during an in-person interview using a validated,
      quantitative food frequency questionnaire. Logistic regression analysis was
      conducted to evaluate the association of nutrients with endometrial cancer risk
      using an energy density method (e.g., nutrient intake/1,000 kilocalories of
      intake). Higher energy intake was associated with increased risk, which was
      attributable to animal source energy and a high proportion of energy from protein
      and fat. Odds ratios comparing highest versus lowest quintiles of intake were
      elevated for intake of animal protein (Odds ratio (OR) = 2.0, 95% confidential
      interval: 1.5-2.7) and fat (OR = 1.5, 1.2-2.0), but reduced for plant sources of
      these nutrients (OR = 0.7, 0.5-0.9 for protein and OR = 0.6, 0.5-0.8 for fat).
      Further analysis showed that saturated and monounsaturated fat intake was
      associated with elevated risk, while polyunsaturated fat intake was unrelated to
      risk. Dietary retinol, beta-carotene, vitamin C, vitamin E, fiber, and vitamin
      supplements were inversely associated with risk. No significant association was
      observed for dietary vitamin B1 or vitamin B2. Our findings suggest that
      associations of dietary macronutrients with endometrial cancer risk may depend on
      their sources, with intake of animal origin nutrients being related to higher
      risk and intake of plant origin nutrients related to lower risk. Dietary fiber,
      retinol, beta-carotene, vitamin C, vitamin E, and vitamin supplementation may
      decrease the risk of endometrial cancer.

PMID- 17230530
TI  - Constant relative survival rates in Sweden and Norway when adjusting for
      screening-related overdiagnosis.

PMID- 17230531
TI  - Formation of depurinating N3Adenine and N7Guanine adducts by MCF-10F cells
      cultured in the presence of 4-hydroxyestradiol.
AB  - Metabolic conversion of endogenous estrogens, estradiol (E2) and estrone (E1), to
      the catechol estrogens 4-hydroxyE1(E2) [4-OHE1(E2)] has been implicated in the
      initiation of cancer in rodents and humans. Evidence collected in our
      laboratories has shown that 4-OHE1(E2) are enzymatically oxidized to E1(E2)-3,4
      quinones [E1(E2)-3,4-Q], which have the potential to damage DNA by forming
      predominantly depurinating adducts, 4-OHE1(E2)-1-N3Ade and 4-OHE1(E2)-1-N7Gua,
      leading to the accumulation of mutations and probably cell transformation. The
      human breast epithelial cell line MCF-10F has been transformed by treatment with
      E2 or 4-OHE2. We have used MCF-10F cells to study the presence of adducts and
      conjugates after treatment with 4-OHE2. To mimic the intermittent exposure of
      breast cells to endogenous estrogens, MCF-10F cells were treated with 1 microM 4
      OHE2 for a 24-h period at 72, 120, 192 and 240 h postplating. Culture media were
      collected at each point, extracted by solid-phase extraction and analyzed by HPLC
      connected with a multichannel electrochemical detector and/or ultraperformance
      liquid chromatography/tandem mass spectrometry. Media from successive treatments
      with 4-OHE2 showed the formation of methoxy and cysteine conjugates, and the
      depurinating adducts 4-OHE1(E2)-1-N3Ade. The amount of 4-OHE1(E2)-1-N3Ade adducts
      was higher after the third treatment; smaller amounts of the 4-OHE1(E2)-1-N7Gua
      adducts were detected after the second and third treatments. These results
      demonstrate that MCF-10F cells oxidize 4-OHE2 to E1(E2)-3,4-Q, which react with
      DNA to form the depurinating N3Ade and N7Gua adducts. This DNA damage can play an
      important role in the 4-OHE2-induced mutations and transformation of MCF-10F
      cells to malignant cells.

PMID- 17230533
TI  - Effects of a catechol-O-methyltransferase inhibitor on catechol estrogen-induced
      cellular transformation, chromosome aberrations and apoptosis in Syrian hamster
      embryo cells.
AB  - To examine a possible mechanism of endogenous estrogen-induced carcinogenesis, we
      studied the effect of the catechol-O-methyltransferase (COMT) inhibitor Ro 41
      0960 on cell transforming and clastogenic activities of 2 catechol estrogens 2-
      and 4-hydroxyestrone (2- or 4-OHE1) using Syrian hamster embryo (SHE) cells. COMT
      activity was assayed by determining the methylation of 2- or 4-OHE1 using gas
      chromatography. The production of 2-methoxyestrone in cultures treated with 2
      OHE1 was approximately 2-fold that of 4-methoxyestrone in cultures treated with 4
      OHE1. 4-OHE1 induced morphological transformation at a higher frequency than 2
      OHE1 did and the frequencies of cell transformation and chromosome aberrations
      were not significantly changed in cells treated with 4-OHE1 in the presence of Ro
      41-0960. In contrast, the frequencies of cell transformation and chromosome
      aberrations were markedly increased in cells treated with 2-OHE1 along with Ro 41
      0960 when compared to cells treated with 2-OHE1 alone. In addition, both catechol
      estrogens induced P53 protein expression and apoptosis. The frequencies of
      apoptotic cells induced by the catechol estrogens were modified by the COMT
      inhibition in a manner similar to those observed with the chromosome aberrations
      assay and the cell transformation assay, indicating that each effect by the
      catechol estrogens at the three measured endpoints might be caused by a mechanism
      similar to the others. Our findings indicate that COMT activity has an influence
      on cell transforming activity and its related genetic effects of catechol
      estrogens in SHE cells, which implies that an individual activity of COMT may be
      one of the etiological factors in endogenous estrogen-induced carcinogenesis.

PMID- 17230532
TI  - Neurotensin stimulates expression of early growth response gene-1 and EGF
      receptor through MAP kinase activation in human colonic epithelial cells.
AB  - Neurotensin (NT) is a highly expressed gastrointestinal (GI) neuropeptide, which
      modulates GI motility, secretion and cell growth as well as intestinal
      inflammation. Since EGF receptor is highly expressed in human colon cancer cells,
      we sought to examine whether NT stimulation contributes to the EGFR
      overexpression using nontransformed colonocyte NCM460 cells. The results show
      that NT treatment caused a significant increase in EGFR protein expression and
      gene transcription. Pretreatment with MAP kinase pathway inhibitor PD98059
      blocked NT-induced EGFR expression. As the EGFR promoter has a functional Egr-1
      site, previously shown to mediate its transcription in response to hypoxia, we
      examined the role of Egr-1 in the NT response. We first show that NT stimulated
      Egr-1 expression, which can be inhibited by PD98059. We also determined whether
      NT increases Egr-1 binding to its site within the EGFR promoter. The data
      indicate that NT enhanced the amount of Egr-1 binding to the EGFR Egr-1 site and
      that this binding was significantly decreased by PD98059. To verify that Egr-1
      mediated NT-induced EGFR transcription, Egr-1 siRNA was used to knock down its
      expression. The data show that transfection of Egr-1 siRNA significantly
      inhibited NT-stimulated EGFR transcription. Together, our results suggest that NT
      can stimulate MAP kinase-mediated Egr-1 and EGFR gene expression in human
      colonocytes. Our results may be relevant to the mechanisms by which NT
      participates in the development of colon cancer.

PMID- 17230534
TI  - DNA demethylation of vascular endothelial growth factor-C is associated with gene
      expression and its possible involvement of lymphangiogenesis in gastric cancer.
AB  - Previous studies have indicated that lymphangiogenesis in solid tumors is
      associated with lymphatic metastasis. Overexpression of Vascular endothelial
      growth factor (VEGF)-C plays a major role in lymphangiogenesis in cancers. In the
      present study, DNA methylation and expression of the VEGF-C gene was investigated
      in gastric cancer (GC). Four GC cell lines (MKN-45, MKN-74, HSC-39 and HSC-43)
      showed no expression of VEGF-C, and the VEGF-C gene was found to be methylated in
      these cells. In contrast, 7 GC cell lines (MKN-1, MKN-7, MKN-28, TMK-1, KATO-III,
      SH101-P4 and HSC-44PE) expressed VEGF-C, and the VEGF-C gene was found to be
      unmethylated in these cell lines. In addition, expression of VEGF-C mRNA was
      retrieved by treatment with a demethylating agent, Aza-2'-deoxycytidine. In GC
      tissue samples, bisulfite DNA sequencing analysis revealed that VEGF-C was not
      methylated in 9 (29.0%) of 31 GC samples, whereas demethylation was not observed
      in corresponding non-neoplastic mucosa samples. Overexpression of VEGF-C mRNA was
      observed in 16 (51.6%) of 31 GC samples by quantitative reverse transcription
      polymerase chain reaction. Of the 9 GC cases with VEGF-C demethylation, 8 (88.9%)
      overexpressed VEGF-C. In contrast, of the 22 GC cases without VEGF-C
      demethylation, 8 (36.4%) overexpressed VEGF-C (p = 0.0155). Furthermore,
      lymphatic vessel density determined by immunostaining of podoplanin in GC tissues
      was associated with overexpression of VEGF-C (p < 0.0001). These results suggest
      that demethylation and activation of the VEGF-C gene is likely involved in
      lymphangiogenesis in GC.

PMID- 17230535
TI  - Preferential expression and frequent IgG responses of a tumor antigen, SOX5, in
      glioma patients.
AB  - We previously reported to identify SOX5 as a glioma antigen by serological
      screening using a testis cDNA library. The present study was designed to analyze
      SOX5 expression, its immunoreactivity, and the correlation between SOX5 IgG
      responses and clinical features in glioma patients to evaluate the possibility of
      its use as a diagnostic marker. Quantitative RT-PCR and Western blot analysis
      revealed that SOX5 was expressed in glioma tissues, but not in normal adult
      tissues, except in the testis. An immunohistochemical analysis showed that SOX5
      was expressed in glioma cells, but only a few SOX5-positive cells were detected
      in non-neoplastic tissues from the cerebral cortex. IgG antibodies against SOX5
      were detected in sera from 8 of the 27 glioma patients (27.6%), 0 of the 14
      patients with other brain diseases (0%), 1 of the 54 other cancer patients (1.9%)
      and 1 of the 37 healthy individuals (2.7%). Patients with glioblastoma (GBM) who
      showed IgG responses against SOX5 exhibited significantly better survival periods
      than GBM patients without SOX5 antibodies. In summary, SOX5 is aberrantly
      expressed in glioma and can be recognized as a glioma antigen using IgGs from the
      sera of glioma patients. Furthermore, there is a statistically significant
      correlation between the presence of SOX5 IgGs and survival in GBM patients,
      suggesting that the glioma antigen SOX5 may be useful not only as a diagnostic
      marker, but also as a prognostic marker in glioma patients.

PMID- 17230536
TI  - Impact of varying pulse frequency and duration on muscle torque production and
      fatigue.
AB  - Neuromuscular electrical stimulation (NMES) involves the use of electrical
      current to facilitate contraction of skeletal muscle. However, little is known
      concerning the effects of varying stimulation parameters on muscle function in
      humans. The purpose of this study was to determine the extent to which varying
      pulse duration and frequency altered torque production and fatigability of human
      skeletal muscle in vivo. Ten subjects underwent NMES-elicited contractions of
      varying pulse frequencies and durations as well as fatigue tests using
      stimulation trains of equal total charge, yet differing parametric settings at a
      constant voltage. Total charge was a strong predictor of torque production, and
      pulse trains with equal total charge elicited identical torque output. Despite
      similar torque output, higher- frequency trains caused greater fatigue. These
      data demonstrate the ability to predictably control torque output by
      simultaneously controlling pulse frequency and duration and suggest the need to
      minimize stimulation frequency to control fatigue.

PMID- 17230537
TI  - Severity, type, and distribution of myotonic discharges are different in type 1
      and type 2 myotonic dystrophy.
AB  - To characterize and compare electrical myotonia in myotonic dystrophy type 1
      (DM1) and type 2 (DM2), 16 patients with genetically confirmed DM1 and 17
      patients with DM2 underwent standardized concentric needle electromyography of
      deltoid, biceps, extensor digitorum communis, first dorsal interosseous, tensor
      fascia lata (TFL), vastus lateralis (VL), tibialis anterior, and thoracic
      paraspinal muscles. Eight needle insertions per muscle were made by
      electromyographers blinded to DM type who recorded the presence and type of
      myotonia (e.g., classic waxing-waning or less specific waning discharges). Manual
      muscle testing was performed by a physical therapist. Overall, myotonia was more
      elicitable in DM1 than DM2; only in VL and TFL was myotonia more elicitable in
      DM2 than DM1. The major type of myotonia was waxing-waning in DM1, and waning in
      DM2. Four DM2 (24%), but no DM1 patients had only waning myotonia. In the arms,
      myotonia was distally predominant in both DM1 and DM2. In the legs, it was
      distally predominant in DM1, but both proximal and distal in DM2. The severity of
      myotonia was positively correlated with muscle weakness and with the presence of
      waxing and waning discharges in DM1, but with neither in DM2. Thus, myotonia is
      qualitatively and quantitatively different in DM1 than DM2. Except for proximal
      leg muscles, myotonia is more evocable in DM1 than DM2. It tends to be waxing
      waning in DM1 but waning in DM2, thus making electrodiagnosis of DM2 more
      challenging. Its severity correlates with muscle weakness and the presence of
      waxing-waning discharges in DM1 but not DM2.

PMID- 17230538
TI  - Enteric ganglioneuritis and abnormal interstitial cells of Cajal: features of
      inflammatory bowel disease.
AB  - BACKGROUND: An increased prevalence of irritable bowel syndrome (IBS) and
      disturbances in cardiac and blood pressure reflexes have been described in
      patients with Crohn's disease (CD) and ulcerative colitis (UC). These features
      could be due to abnormalities in the gastrointestinal neurotransmission. The aims
      of this study were to examine whether histopathologic changes in the enteric
      nervous system correlate with disturbances in cardiac and blood pressure reflexes
      and the occurrence of IBS- and dyspepsia-like symptoms in these patients.
      METHODS: Thirty patients with CD and UC with bowel resection were examined by
      deep-breathing and orthostatic tests. The resection specimens were evaluated
      histologically regarding visceral neuro- or myopathy. All medical records were
      studied for treatment and clinical course. RESULTS: Ganglioneuritis was observed
      in 11 of 19 patients with CD and in 5 of 11 with UC. Only patients with CD had
      ganglioneuritis in the small intestine. Moreover, in CD the interstitial cells of
      Cajal (ICCs) in the small bowel showed atrophy and vacuolar degeneration, along
      with a reduced number of cells (P = 0.005). In UC the colonic ICCs were
      hyperplastic (P = 0.05) without signs of degeneration. The indices of deep
      breathing and orthostatic tests were impaired, except in CD with ganglioneuritis,
      who showed normal test values. There were no correlations between histopathologic
      alterations versus IBS and dyspepsia. CONCLUSIONS: Visceral ganglioneuritis and
      pathologic ICCs were observed in patients with CD and UC. However, these
      histopathologic abnormalities could not be related to the clinical or autonomic
      features of the disease.

PMID- 17230539
TI  - Colonic expression of leukotriene-pathway enzymes in inflammatory bowel diseases.
AB  - BACKGROUND: Leukotrienes derived from the 5-lipoxygenase pathway are
      proinflammatory lipid mediators that possibly play a role in inflammatory bowel
      diseases. The expression of 5-lipoxygenase pathway proteins has not previously
      been examined in colonic mucosa in inflammatory bowel disease. RESULTS:
      Quantitative immunohistochemical analyses showed that, compared to those of the
      control subjects (n = 9), colonic biopsies from patients with active inflammatory
      bowel disease (n = 17) had 3- to 7-fold higher mean counts of cells expressing 5
      lipoxygenase (P = 0.03), 5-lipoxygenase-activating protein (P = 0.005), and the
      leukotriene A(4) hydrolase (P = 0.004), which make up the biosynthetic pathway of
      the potent neutrophil chemotaxin leukotriene B(4). Immunoexpression of the
      leukotriene C(4) synthase was unaltered (P > 0.2). The increased representation
      of leukotriene B(4)-pathway enzymes was associated with higher counts of
      neutrophils (P = 0.0001), macrophages (P = 0.03), eosinophils (P = 0.0004),
      CD8(+) T cells (P < 0.001), activated T cells (P < 0.05), and B cells (P < 0.05)
      but not of mast cells (P > 0.9). These eicosanoid and cellular changes were most
      marked in the subgroup of patients with ulcerative colitis (n = 9), and were
      absent in patients with quiescent disease (n = 6). The anomalies in the 5
      lipoxygenase pathway were accompanied as expected by more cells immunostaining
      for cytokine-inducible COX-2 (P = 0.004, n = 17), but this study also revealed a
      greater number of cells expressing COX-1 in the samples from the patients in the
      ulcerative colitis subgroup (P = 0.03, n = 9). CONCLUSIONS: The 5-lipoxygenase
      data provide a cellular basis for increased tissue synthesis of the leukotriene
      B(4), as reflected in the colonic mucosa and rectal dialysates of patients with
      active inflammatory bowel disease, which contributes to neutrophil influx and
      colonic injury. The COX-1/COX-2 data highlight the ambiguous functional role of
      prostanoid pathways in inflammatory bowel diseases.

PMID- 17230540
TI  - Population-based case-control study of measles, mumps, and rubella and
      inflammatory bowel disease.
AB  - BACKGROUND: Previous controversy was generated over the hypothesis that a
      paramyxovirus such as measles or vaccination against such viruses might be
      causally associated with inflammatory bowel disease (IBD). We aimed to determine
      if Crohn's disease (CD) or ulcerative colitis (UC) subjects are more likely to be
      seropositive for measles, mumps, or rubella than controls. METHODS: Using our
      population-based University of Manitoba IBD Research Registry we recruited CD (n
      = 235) and UC (n = 137) subjects ages 18-50 years for a study involving detailed
      questionnaires and venipuncture. We accessed the population-based databases of
      Manitoba Health (single provincial health insurer) to get age-, gender-, and
      geography-matched non-IBD controls (n = 310). We used a standard enzyme-linked
      immunosorbent assay (ELISA) to measure serum antibodies. RESULTS: Seropositivity
      for measles and mumps was similar in controls (98.1%, 78.4%, respectively) as in
      CD (96.2%, 72.3% respectively) and in UC (95.5%, 74.6%, respectively). However,
      controls were significantly more likely to be seropositive for rubella (98.1%)
      than were CD cases (91.0%, P < 0.0002) or UC cases (93.3%, P = 0.01). Males
      accounted for the significantly lower rates of seropositivity to rubella with CD.
      While we determined that significantly more controls than CD were vaccinated, we
      cannot be sure if the increased rate of rubella seropositivity in controls is
      secondary to wildtype or vaccine-associated infection. CONCLUSIONS: These data
      suggest there is no association of having acquired measles, mumps, or rubella (by
      natural infection or through vaccination) and CD or UC. If anything, these data
      may suggest some protective effect of having acquired rubella infection or
      vaccine against acquiring CD.

PMID- 17230541
TI  - Retracted: Factors affecting hospital readmission rates for breast cancer
      patients in Western Australia.
AB  - By this notice, the Editor and the Publisher of the Journal of Surgical Oncology
      retract from publication the following article: "Factors Affecting Hospital
      Readmission Rates for Breast Cancer Patients in Western Australia," Michael A.
      Martin, Ramona Meyricke, Terry O'Neill, and Steven Roberts, Journal of Surgical
      Oncology, Published online January 17, 2007, DOI: 10.1002/jso.20742. The article
      has been formally deemed a duplicate submission. The Editor and the Publisher of
      the Journal of Surgical Oncology regret the occurrence of this unfortunate
      incident. 

PMID- 17230542
TI  - A simple method to accurately position Port-A-Cath without the aid of
      intraoperative fluoroscopy or other localizing devices.
AB  - BACKGROUND: To evaluate the efficacy and acceptability of the Port-A-Cath (PAC)
      insertion method with (conventional group as II) and without (modified group as
      I) the aid of intraoperative fluoroscopy or other localizing devices. METHODS: A
      total of 158 women with various kinds of gynecological cancers warranting PAC
      insertion (n = 86 in group I and n = 72 in group II, respectively) were
      evaluated. Data for analyses included patient age, main disease, dislocation
      site, surgical time, complications, and catheter outcome. RESULTS: There was no
      statistical difference between the two groups in terms of age, main disease,
      complications, and the experiencing of patent catheters. However, appropriate
      positioning (100% in group I, and 82% in group II) in the superior vena cava
      (SVC) showed statistical differences between the two groups (P = 0.001). In
      addition, the surgical time in group I was statistically shorter than that in
      group II (P < 0.001). CONCLUSIONS: The modified method for inserting the PAC
      offered the following benefits: including avoiding X-ray exposure for both the
      operator and the patient, defining the appropriate position in the SVC, and less
      surgical time.

PMID- 17230543
TI  - The case for routine use of adjuvant therapy in pancreatic cancer.
AB  - Pancreatic cancer is a devastating disease with a poor prognosis for most
      patients. Surgical resection remains the cornerstone of treatment, providing the
      only realistic hope of long-term survival. Even with optimal surgical management,
      5-year survival averages 15% to 20% for resectable disease. Progress is being
      made, however. Currently, the benefits of postoperative therapy for resected
      pancreatic ductal adenocarcinoma appear clear, and recommendations for such
      therapy appear to us to be well justified. Additional benefit to patients awaits
      the development of new agents, molecular targeted drugs, and novel approaches
      such as immunotherapy.

PMID- 17230544
TI  - Estrogen sulfotransferase (SULT1E1) expression in benign and malignant human bone
      tumors.
AB  - BACKGROUND AND OBJECTIVES: 17beta-estradiol regulates growth and differentiation
      in normal and malignant bone. E2 is inactivated to 17beta-estradiol-sulfate
      through estrogen sulfotransferase (SULT1E1). RESULTS: In an explorative study,
      SULT1E1 mRNA expression was assessed in a broad range of samples from benign,
      primary and secondary malignant bone tumors. We detected SULT1E1 mRNA in 31/50
      tumor samples (10/19 malignant, 6/13 benign tumors; 15/18 metastases).
      Significantly more SULT1E1-positive samples were found in metastases than in
      primary bone tumors (P = 0.019). Yet, there was no difference between malignant
      and benign primary tumors (P = 0.718). SULT1E1 mRNA levels were not related to
      patients' age, gender, tumor location, stage, grading, and chemotherapy
      pretreatment. Relative SULT1E1 mRNA levels did not correlate with that of
      estrogen-receptor alpha (ERalpha) as assessed by quantitative TaqMan PCR (10
      malignant, 8 benign tissue samples). In the latter, ERalpha mRNA, but not SULT1E1
      mRNA levels were significantly lower than in the malignant samples (P = 0.006 and
      P = 0.71, respectively). Also, pronounced expression of SULT1E1 mRNA but not of
      ERalpha mRNA was observed in osteosarcoma (MG-63, HOS) and Ewing's sarcoma (TC
      71) cells, while human osteoblasts and BMSC contained ERalpha but not SULT1E1
      mRNA. CONCLUSION: Frequent expression of SULT1E1 mRNA in various human bone
      tumors suggests that sulfonation might be important to control E2 levels and
      activity.

PMID- 17230545
TI  - Transradial approach for carotid artery stenting: a feasibility study.
AB  - BACKGROUND: Carotid artery stenting (CAS) has become accepted as an alternative
      to carotid endarterectomy for revascularization of the internal carotid artery
      (ICA) among high risk patients. CAS from the femoral approach can be problematic
      due to access site complications as well as technical difficulties related to
      peripheral vascular disease (PVD) and/or anatomical variations of the aortic
      arch. The purpose of the present study is to evaluate the feasibility of the
      radial artery as an alternative approach for CAS. METHODS: Forty-two patients
      (mean age 71 +/- 1, 26 male) underwent CAS. All had a CA stenosis greater than
      80% and comorbid conditions increasing the risk of carotid endarterectomy. The
      target common carotid artery (CCA) was initially cannulated via the radial artery
      using a 5F Simmons 1 diagnostic catheter which was then advanced to the external
      CA (ECA) over an extra support 0.014" coronary guidewire. After removing the
      coronary guidewire, a 0.035" guidewire was advanced into the ECA, and the Simmons
      1 was exchanged for a 5F or 6F shuttle sheath and positioned in the distal CCA.
      In four patients with a bovine aortic arch, the left CCA was accessed with a 5F
      Amplatz R2 catheter which was then exchanged for a shuttle sheath over a 0.035"
      guidewire. CAS was performed using standard techniques with weight-based
      bivalirudin for anticoagulation. RESULTS: CAS was successful in 35/42 (83%)
      patients, including 28/29 (97%) right CA, 4/5 (80%) bovine left CA, 7/13 (54%)
      left CA. Mean interventional time was 30 +/- 3 minutes. The sheath was removed
      immediately after the procedure. There were no radial access site complications.
      One patient sustained a stroke 24 hrs after the procedure with complete
      resolution of symptoms (Mean NIH stroke scale 2.0 +/- 0.3 before, 1.9 +/- 0.3
      after). Median hospital stay was 2 +/- 0.6 days. Inadequate catheter support at
      the origin of the CCA was the technical cause of failure in the seven
      unsuccessful cases. CONCLUSION: CAS using the transradial approach appears to be
      safe and technically feasible. The technique may be particularly useful in
      patients with right ICA lesions and severe PVD or unfavorable arch anatomy, and
      among patients with a bovine aortic arch.

PMID- 17230547
TI  - Cathepsin K and schizophrenia.

PMID- 17230546
TI  - PET imaging of neurokinin-1 receptors with [(18)F]SPA-RQ in human subjects:
      assessment of reference tissue models and their test-retest reproducibility.
AB  - [(18)F]SPA-RQ (substance P antagonist receptor quantifier) labels the substance P
      preferring (NK(1)) receptor in human brain. A prior study showed that [(18)F]SPA
      RQ brain uptake can be quantified with a reference tissue method and thereby
      avoid invasive blood sampling. The purposes of this study were to compare three
      different reference tissue methods and to assess test-retest reproducibility.
      Eight healthy subjects underwent two [(18)F]SPA-RQ scans. We calculated the
      binding potential (BP), which is proportional to receptor density, from both
      regional volume of interest and voxel-wise data. We compared three reference
      tissue methods: simplified reference tissue model, multilinear reference tissue
      model (MRTM), and its two-parameter version (MRTM2). The three methods generated
      equivalent values of regional BP, but MRTM2 was the most resistant to noise.
      Temporally stable values of BP were obtained with 240 min of imaging data. MRTM2
      had excellent test-retest reproducibility, with high reliability (intraclass
      correlation > 0.9) and low variability (< 10%). In addition to regional volume of
      interest analysis, we also created parametric images of BP, variability, and
      reliability based on voxel-wise time-activity data. The reproducibility of
      parametric BP was also good, with variability < 20% and reliability > 0.7 in gray
      matter regions. In conclusion, a two-parameter reference tissue method (MRTM2)
      provided reproducible and reliable measurements of [(18)F]SPA-RQ brain uptake
      using 240 min of both regional and voxel-wise data.

PMID- 17230548
TI  - Methamphetamine blood concentrations in human abusers: application to
      pharmacokinetic modeling.
AB  - Characterization of methamphetamine's (METH) dose-dependent effects on brain
      neurochemistry may represent a critical component for better understanding the
      range of resultant behavioral pathologies. Most human studies, however, have
      assessed only the effects of long term, high dose METH abuse (e.g., greater than
      1000 mg/day) in individuals meeting DSM-IV criteria for METH dependence. Yet, for
      the majority of METH abusers, their patterns of METH exposure that consist of
      lower doses remain less well-characterized. In this study, blood samples were
      obtained from 105 individuals detained by police for possible criminal activity
      and testing positive for stimulants by EMIT assay. METH blood concentrations were
      subsequently quantified by GC-MS and were predominantly in the low micromolar
      range (0.1-11.1 microM), with median and mean values of 1.3 microM (0.19 mg/l)
      and 2 microM (0.3 mg/l), respectively. Pharmacokinetic calculations based on
      these measured values were used to estimate initial METH body burdens, the median
      value being 52 mg. Modeling a 52 mg dose for a 4 day-METH maintenance exposure
      pattern of 4 doses/day at 4 h intervals showed that blood concentrations remained
      between 1 and 4 microM during this period. Collectively, these data present
      evidence for a METH exposure pattern distinct from high dose-METH abuse and
      provide the rationale for assessing potential brain pathology associated with
      such lower dose-METH exposure.

PMID- 17230549
TI  - Signaling by hepatocyte growth factor in neurons is induced by pharmacological
      stimulation of synaptic activity.
AB  - Activity-dependent signaling by growth factors is hypothesized to link synaptic
      activity to structural and functional modifications of neurons. The receptor
      tyrosine kinase Met and its ligand, hepatocyte growth factor (HGF), are clustered
      at excitatory synapses and may regulate aspects of excitatory synaptic function,
      as HGF increases expression of excitatory synaptic proteins, enhances their
      clustering at sites along dendrites, and increases current through the NMDA
      receptor. In this article, we test for secretion or activation of HGF and for
      activation of Met in response to pharmacological stimulation of synaptic
      activity. Stimulation of dissociated hippocampal neuron cultures with glutamate
      caused increased immunocytochemical staining against HGF on nonpermeabilized
      cells. Glutamate treatment also decreased the amount of pro HGF and increased the
      amount of the proteolytically-activated HGF in immunoblots of neuron culture
      lysates, and increased the levels of activated HGF in culture media. Stimulation
      of neuron cultures with glutamate or bicuculline induced autophosphorylation of
      Met on dendrites and the soma of neurons. Pretreatment of neurons with glutamate
      receptor inhibitors prior to glutamate treatment blocked autophosphorylation of
      Met. These results suggest that HGF can participate in activity-dependent
      signaling in neurons.

PMID- 17230550
TI  - Dissociation between apoptosis, neurogenesis, and synaptic potentiation in the
      dentate gyrus of adrenalectomized rats.
AB  - Removal of adrenal hormone corticosterone in rats aged 3-4 months results within
      3 days in acceleration of apoptosis and proliferation of newborn cells in the
      dentate gyrus (DG). A critical question is whether such a shift in the maturity
      of dentate cells after adrenalectomy (ADX) affects synaptic plasticity. To
      address this question, male rats were adrenalectomized and synaptic potentiation
      was recorded in vitro in hippocampal slices, as well as in vivo, in response to
      high frequency stimulation of the perforant path, 3 days after ADX. At this time
      point, cell loss was assessed and proliferation was examined. Based on two
      independent parameters, bromodeoxyuridine and Ki-67, we found that removal of the
      adrenal glands increases proliferation rate. This increase in proliferation was,
      in particular, evident in those animals that displayed substantial cell loss. The
      accelerated cell-turnover after ADX was accompanied by reduced synaptic
      potentiation, both when recorded in vitro and in vivo. Corticosterone replacement
      in vivo (in adrenalectomized animals), at levels that activate the
      mineralocorticoid receptor, prevented ADX-induced proliferation, apoptosis, and
      restored synaptic potentiation to control levels. Importantly, corticosterone
      applied to slices from adrenalectomized rats also normalized synaptic
      potentiation, despite increased proliferation. This suggests that changes in cell
      proliferation and apoptotic cell death in the DG are not necessarily key factors
      determining the efficacy of synaptic potentiation.

PMID- 17230551
TI  - Dopamine activity in the occipital and temporal cortices of rats: dissociating
      effects of sensory but not pharmacological stimulation.
AB  - Little is known about the functional role of DA in other cortical areas than in
      the prefrontal cortex. Here we demonstrate that visual stimulation increases DA
      activity as measured by in vivo microdialysis in the occipital, but not in the
      temporal cortex of freely moving rats. Auditory stimulation neither acutely
      affected DA in the occipital nor in the temporal cortex. A pharmacological
      challenge with cocaine (0, 5, 10, 20 mg/kg; i.p.) increased DA levels in both
      areas dose-dependently. These data suggest that DA might play a role in visual
      processing selectively in the occipital cortex. Furthermore, the results indicate
      that DA in both regions may contribute to cocaine's behavioral effects.

PMID- 17230552
TI  - Waved-1 mutant mice are hypersensitive to the locomotor actions of cocaine.
AB  - Transforming growth factor-alpha (TGFalpha) is a well-known regulator of many
      developmental processes, and is expressed heavily in basal forebrain and striatal
      regions. When TGFalpha is reduced in Waved-1 (Wa-1) mutant mice, brain anatomy,
      biogenic amines, stress response, and behavior are normal prior to, but altered
      following puberty. As an initial screen for possible alterations in nigrostriatal
      and mesolimbic dopamine (DA) systems, we tested adult Wa-1 mutant mice in an open
      field, following acute injection with cocaine (15 mg/kg). Wa-1 mice exhibited
      significantly greater ambulatory distance, number of ambulatory episodes, and
      cocaine-induced motor stereotypies than do controls. These data indicate that
      adult Wa-1 mice are hypersensitive to the locomotor effects of cocaine and
      provide a new potential link between neurodevelopmental processes and adult
      psychostimulant responsiveness.

PMID- 17230553
TI  - Agonist-dependent internalization of D2 receptors: Imaging quantification by
      confocal microscopy.
AB  - In positron emission tomography and single photon emission computed tomography
      studies using D2 dopamine (DA) receptor radiotracers, a decrease in radiotracer
      binding potential (BP) is usually interpreted in terms of increased competition
      with synaptic DA. However, some data suggest that this signal may also reflect
      agonist (DA)-induced increases in D2 receptor (D2R) internalization, a process
      which would presumably also decrease the population of receptors available for
      binding to hydrophilic radioligands. To advance interpretation of alterations in
      D2 radiotracer BP, direct methods of assessment of D2R internalization are
      required. Here, we describe a confocal microscopy-based approach for the
      quantification of agonist-dependent receptor internalization. The method relies
      upon double-labeling of the receptors with antibodies directed against
      intracellular as well as extracellular epitopes. Following agonist stimulation,
      DA D2R internalization was quantified by differentiating, in optical cell
      sections, the signal due to the staining of the extracellular from intracellular
      epitopes of D2Rs. Receptor internalization was increased in the presence of the
      D2 agonists DA and bromocriptine, but not the D1 agonist SKF38393. Pretreatment
      with either the D2 antagonist sulpiride, or inhibitors of internalization
      (phenylarsine oxide and high molarity sucrose), blocked D2-agonist induced
      receptor internalization, thus validating this method in vitro. This approach
      therefore provides a direct and streamlined methodology for investigating the
      pharmacological and mechanistic aspects of D2R internalization, and should inform
      the interpretation of results from in vivo receptor imaging studies.

PMID- 17230554
TI  - In vivo mapping of substance P receptors in brains of laboratory animals by high
      resolution imaging systems.
AB  - Neurotransmission mediated by substance P (SP) and NK(1) receptor has been
      implicated in the pathophysiology of analgesia, emesis and diverse
      neuropsychiatric conditions including depression and anxiety disorder. Several
      lines of clinical trials using NK(1) receptor antagonists have been conducted to
      date, and the efficiency of preclinical assessments for proof of concept and dose
      optimization could be greatly increased by configuring an in vivo analytical
      system that permits quantitative mapping of NK(1) receptors in the brains of
      small-size laboratory animals expressing "human-like" NK(1) receptors. Hence, we
      investigated the applicability of experimental animals, ranging from rodents to
      primates, to positron emission tomographic (PET) measurements with
      [(18)F]fluoroethyl-SPA-RQ, a modification of a recently established radioligand
      for NK(1) receptors. A pharmacokinetic assay could be performed for a rhesus
      monkey in an awake condition, which allows the circumvention of influences of
      anesthesia on SP neurotransmission. Coregistration of PET and magnetic resonance
      images acquired by small-animal-dedicated devices enabled detailed localization
      of NK(1) receptors in the gerbil and marmoset brains. The present study also
      revealed the potentials of SDZ NKT 343 as an antagonist for central NK(1)
      receptors. In conjunction with additional in vitro and ex vivo autoradiographic
      observations, our in vivo results have demonstrated a similarity in the binding
      pattern among the animals examined, justifying cross-species extrapolation of PET
      findings on the SP-NK(1) pathway.

PMID- 17230555
TI  - Do pre-irradiation dental extractions reduce the risk of osteoradionecrosis of
      the mandible?
AB  - BACKGROUND: This study was done to determine if pre-radiotherapy (pre-RT) dental
      extractions reduce the risk of osteoradionecrosis (ORN). METHODS: Between 1987
      and 2004, 413 patients with oropharyngeal carcinomas were treated with definitive
      RT at the University of Florida. Dentate patients underwent pretreatment dental
      evaluation. Teeth in the RT field were usually extracted if thought to have poor
      long-term prognosis from dental disease. The endpoint was > or = grade 2 ORN
      using a modified staging system. Patients were excluded for local recurrence,
      additional RT above the clavicles, or head and neck surgery besides neck
      dissection. RESULTS: ORN rates were as follows: edentulous, <1%; teeth in-field
      with pre-RT extractions, 15%; and teeth in-field without pre-RT extractions, 9%.
      Patients with poor in-field teeth and pre-RT extractions had a higher 5-year
      incidence of ORN than those who did not have pre-RT extractions (16% vs 6%, p =
      .48). Likewise, for those with in-field teeth in good condition and pre-RT
      extractions, the 5-year ORN incidence was higher than for those who did not
      undergo extractions (15% vs 2%, p = .42). Multivariate analysis revealed
      increased ORN risk with doses of >70 Gy, once-daily fractionation, or
      brachytherapy. CONCLUSION: Pre-RT extractions do not appear to reduce the risk of
      ORN.

PMID- 17230556
TI  - Current topics in the epidemiology of oral cavity and oropharyngeal cancers.
AB  - Oral cancer incidence rates rose dramatically during the twentieth century in the
      United States and Europe, especially among individuals under the age of 60 years.
      Although influenced by age, sex, and country of origin, incidence trends were
      most strongly affected by elevated risk among individuals born after
      approximately 1915. This cohort effect was indicative of strong behavioral
      influences on oral cancer risk. In this article, associations between oral cancer
      risk and established behavioral risk factors including alcohol and tobacco use
      are reviewed. Additionally, possible associations between oral cancer risk and
      oral hygiene, diet, nutritional status, and sexual behavior as well as the
      influence of genetic factors on oral cancer risk are considered. Special emphasis
      is placed on evaluating possible risk differences in individuals above and below
      the age of 45 and in users and nonusers of alcohol and tobacco.

PMID- 17230557
TI  - Management of Frey syndrome.
AB  - Almost all patients who undergo parotidectomy will to some extent develop Frey
      syndrome (auriculotemporal syndrome or gustatory sweating) after surgery, because
      of aberrant regeneration of cut parasympathetic fibers between otic ganglion and
      subcutaneous vessels. However, only the minority of these patients needs
      treatment. The syndrome consists of gustatory sweating, flushing, and warming
      over the preauricular and temporal areas. Thick skin flap and partial superficial
      parotidectomy are the most important techniques to minimize the risk of
      developing symptomatic Frey syndrome. Intracutaneous injection of botulinum toxin
      A is an effective, long-lasting, and well-tolerated treatment of Frey syndrome.
      If recurrence occurs, the treatment can be repeated.

PMID- 17230558
TI  - Effects of radiotherapy with or without chemotherapy on tongue strength and
      swallowing in patients with oral cancer.
AB  - BACKGROUND: Oral tongue strength and swallowing ability are reduced in patients
      treated with chemoradiotherapy for oral and oropharyngeal cancer. METHODS:
      Patients with oral or oropharyngeal cancer treated with high-dose
      chemoradiotherapy underwent tongue strength, swallowing, and dietary assessments
      at pretreatment and 1, 3, 6, and 12 months posttreatment. Tongue strength was
      assessed using the Iowa Oral Performance Instrument (IOPI). Oral and pharyngeal
      residue was evaluated utilizing videofluoroscopy. RESULTS: Mean maximum tongue
      strength dropped a nonsignificant amount immediately after treatment, and then
      increased significantly at 6- and 12-months posttreatment completion. Analyses
      were adjusted for patient dropout. Tongue strength was not significantly
      correlated with swallow observations of percentage oral and pharyngeal residue.
      Ability to eat various diet consistencies was reduced after treatment but
      improved over time at a rate similar to changes in oral intake and type of diet.
      CONCLUSIONS: Parallel but not significant changes in oral intake, diet, and
      tongue strength in the first year post chemoradiation therapy need further study
      in a larger population.

PMID- 17230559
TI  - Restoration of wild-type p53 function in human cancer: relevance for tumor
      therapy.
AB  - BACKGROUND: In the majority of human cancers, the tumor suppressor activity of
      p53 is impaired because of mutational events or interactions with other proteins
      (ie, MDM2). The loss of p53 function is responsible for increased aggressiveness
      of cancers, while tumor chemoresistance and radioresistance are dependent upon
      the expression of mutant p53 proteins. METHODS: Review of the literature
      indicates that p53 acts primarily as a transcription factor whose function is
      subject to a complex and diverse array of covalent post-translational
      modifications that markedly influence the expression of p53 target genes
      responsible for cellular responses such as growth arrest, senescence, or
      apoptosis. The ability of p53 to induce apoptosis in cancer cells is believed
      essential for cancer therapy. RESULTS: Numerous data indicate that p53 dependent
      apoptosis is a relevant factor in determining the efficacy of anticancer
      treatments. Thus, the development of new strategies for restoration of p53
      function in human tumors is considered an important issue. Two main approaches
      for restoration of p53 function have been pursued that impact anticancer
      treatments: (a) de novo expression of wild-type p53 (wt-p53) through gene therapy
      and (b) identification of small molecules reactivating wt-p53 function.
      CONCLUSIONS: The extensive body of knowledge acquired has identified
      manipulations of p53 signaling as a relevant issue for successful therapies. In
      this context, the recognition of p53 status in cancer cells is significant and
      would help considerably in the selection of an appropriate therapeutic approach.
      p53 manipulations for cancer therapy have revealed the need for specificity of
      p53 activation and ability to spare body tissues. Furthermore, the promising
      results obtained by using molecules competent to reactivate wt-p53 functions in
      cancer cells provide the basis for the design of new molecules with lower side
      effects and higher anti-tumor efficiency. The reexpression and reactivation of
      p53 protein in human cancer cells would increase tumor susceptibility to
      radiation or chemotherapy enhancing the efficacy of standard therapeutic
      protocols.

PMID- 17230560
TI  - Cutaneous head and neck squamous cell carcinoma metastatic to parotid and
      cervical lymph nodes.
AB  - Nonmelanoma skin cancers occur at an epidemic rate in Australia and are
      increasing in incidence worldwide. In most patients, local treatment is curative.
      However, a subset of patients will be diagnosed with a high-risk cutaneous
      squamous cell carcinoma (SCC) and are defined as patients at increased risk of
      developing metastases to regional lymph nodes. Patients with high-risk SCC may be
      identified based on primary lesion and patient factors. Most cutaneous SCC arises
      on the sun-exposed head and neck. The parotid and upper cervical nodes are common
      sites for the development of metastases arising from ear, anterior scalp,
      temple/forehead, or scalp SCC. The mortality and morbidity associated with high
      risk cutaneous SCC is usually a consequence of uncontrolled metastatic nodal
      disease and, to a lesser extent, distant metastases. Patients with operable nodal
      disease have traditionally been recommended for surgery. The efficacy of adjuvant
      radiotherapy has previously been questioned based on weak evidence in the early
      literature. Recent evidence from larger studies has, however, strengthened the
      case for adjuvant radiotherapy as a means to improve locoregional control and
      survival. Despite this, many patients still experience relapse and die. Research
      aimed at improving outcome such as a randomized trial incorporating the addition
      of chemotherapy to adjuvant radiotherapy is currently in progress in Australia
      and New Zealand. Ongoing research also includes the development of a proposed new
      staging system and investigating the role of molecular factors such as the
      epidermal growth factor receptor.

PMID- 17230561
TI  - Multiple intraosseous hemangiomas-investigation and role of N-butylcyanoacrylate
      in management.
AB  - BACKGROUND: Primary intraosseous hemangiomas are rare (0.7% of all osseous
      neoplasms), benign, slow-growing neoplasms. These lesions are usually solitary.
      We are reporting a case of multicentric intraosseous hemangiomas. Investigation,
      treatment options, and role of N-butylcyanoacrylate (NBCA) in management will be
      discussed. METHODS AND RESULTS: A 20-year-old man had multicentric intraosseous
      hemangiomas involving the skull bones, mandible, vertebra, pelvic bone, and
      tibial tuberosity. N-butylcyanoacrylate was used by direct puncture technique
      using a transosseous transcutaneous route to control profuse bleeding from the
      retromolar region. CONCLUSION: To the best of our knowledge, this is the first
      reported case with such extensive multicentric intraosseous hemangiomas. N
      butylcyanoacrylate by direct puncture technique can be an effective method to
      devascularize and stabilize low-flow intraosseous vascular tumors.

PMID- 17230562
TI  - Informed consent in advanced laryngeal cancer.
AB  - PURPOSE: This study was designed to evaluate the relationship between the
      informed consent process and the treatment received by patients with advanced
      laryngeal cancer. METHODS: The study group was composed of 101 consecutive
      patients who were eligible for the Department of Veterans Affairs Laryngeal
      Cancer Study Group and Radiation Therapy Oncology Group/Head and Neck Intergroup
      (RTOG 91-11) larynx preservation clinical trials and who underwent treatment at
      the Mayo Clinic during the years 1985 to 2000. Records were reviewed to evaluate
      the effect that referral to an oncologist, discussion and documentation of
      treatment alternatives by the surgeon, offering a chance at a larynx conservation
      surgical procedure, and treatment recommendation made by the surgeon have on the
      treatment chosen and received by the patient. RESULTS: Discussion of treatment
      alternatives by the surgeon (p = .0054), referral to an oncologist (p < .0001),
      offering a chance for a larynx conservation surgical procedure (p = .047), and
      treatment recommended by the surgeon (p < .0001) were significantly related to
      the treatment received by the patient. CONCLUSION: The treatment received by a
      patient with advanced laryngeal cancer is determined by the treatment recommended
      by the surgeon, referral to an oncologist, discussion of treatment alternatives
      by the surgeon, and offering a chance for a larynx conservation surgical
      procedure.

PMID- 17230564
TI  - Epithelioid osteosarcoma presenting as a rapidly expanding maxillary mass.
AB  - BACKGROUND: Osteosarcomas of the jaws account for less than 10% of reported
      neoplasms of this type. Patients with osteosarcoma in this region tend to be in
      the late-third to mid-fourth decades of life. The osteoblastic, chondroblastic,
      and fibroblastic variants constitute the majority of lesions. METHODS: A mass was
      observed in the maxilla of a 50-year-old male who presented for a complete
      odontectomy. Over the ensuing weeks, the mass substantially increased in size,
      despite multimodality treatment efforts. RESULTS: Radiographic findings revealed
      a mixed density mass of the left maxilla. Histologic, immunohistochemical, and
      electron microscopy examination of the tumor showed a malignant mesenchymal
      neoplasm consisting of sheets of epithelioid and spindle cells exhibiting focal
      osteoid formation. CONCLUSIONS: We report a rare and aggressive case of
      epithelioid osteosarcoma arising in the maxillofacial complex.

PMID- 17230563
TI  - Infrahyoid fascio-myocutaneous flap as an alternative to free radial forearm flap
      in head and neck reconstruction.
AB  - BACKGROUND: The use of microvascular free flaps is currently the favored method
      for the reconstruction of defects after resection of head and neck cancer. The
      flap most commonly used for head and neck reconstruction is the free radial
      forearm flap, but the less popular infrahyoid flap represents a good alternative
      in selected cases. This flap has proven to be helpful in the reconstruction of a
      wide range of moderate-sized head and neck defects. METHODS: We reviewed a series
      of 13 patients with defects resulting from cancer of the head and neck, who
      underwent infrahyoid flap reconstruction as an alternative to free radial forearm
      flap. The series includes 12 squamous cell carcinomas arising from the oral
      cavity and oropharynx, and 1 Merkel cell carcinoma of the submental skin. In the
      harvesting of the flap, the technical modifications recently suggested by Dolivet
      et al were used in all cases. Furthermore, another technical change has been
      introduced so creating a new infrahyoid facio-myocutaneous flap (IHFMCF). The
      surgical technique is described in detail. RESULTS: No total or partial flap
      necrosis was experienced. All reconstructions healed quickly without wound
      complications and with good functional results. The healing process in the donor
      site was excellent in every case with good aesthetic results. CONCLUSIONS: The
      IHFMCF is a versatile, reliable, and convenient flap suitable for repairing small
      and medium-sized defects of the oral cavity and oropharynx and obviates the need
      for a microvascular reconstruction.

PMID- 17230565
TI  - Cytologic diagnosis of columnar-cell lesions of the breast.
AB  - This study describes the cytologic features of breast columnar-cell lesions
      (CCLs) and determines whether these lesions can be diagnosed by fine-needle
      aspiration. We present ten cases of biopsy-proven CCL with prior fine-needle
      aspiration material and discuss the spectrum of changes, as well as features
      important in the cytologic distinction of CCL from diagnostic mimics. CCLs were
      characterized by flat sheets of cells with enlarged nuclei, distinct cell
      borders, and finely granular cytoplasm. Cytologic atypia ranged from minimal to
      severe, and many cases (8/10) exhibited a paucity of myoepithelial cells. CCL
      showed significant cytologic overlap with papillary neoplasms and well
      differentiated adenocarcinomas. The prospective diagnosis of CCL cannot reliably
      be made by fine-needle aspiration. However, it is important to recognize the
      range of cytologic atypia that can be seen with CCL to avoid an overdiagnosis of
      malignancy.

PMID- 17230566
TI  - Kallikrein 4 is expressed in malignant mesothelioma--further evidence for the
      histogenetic link between mesothelial and epithelial cells.
AB  - The objective of this study was to analyze Kallikrein 4 protein (hK4) expression
      in effusions and solid tumors of patients diagnosed with malignant mesothelioma
      (MM) and compare hK4 expression in MM with that in breast and ovarian
      adenocarcinomas. Sections from 65 MM (21 effusions, 44 solid tumors) and 63
      breast carcinomas (28 effusions, 35 solid tumors) were stained for hK4 using
      immunohistochemistry. Results were compared with our previously published data
      for 284 ovarian carcinomas (181 effusions, 103 solid tumors). Expression of hK4
      was detected in 26/65 (40%) MM and 52/63 (83%) breast carcinomas. Ovarian
      carcinoma showed staining values that were comparable to those in breast
      carcinoma (expression of hK4 in 144/181; 80% effusions and 85/103; 83% solid
      tumors). As opposed to our previous findings in ovarian carcinoma, hK4 expression
      was higher in solid tumors when compared with to effusions in both MM (P = 0.013)
      and breast carcinoma (P = 0.002). Comparative analysis of the three tumor types
      showed significantly higher expression in ovarian and breast adenocarcinomas when
      compared with MM (P < 0.001). In conclusion, hK4 is frequently expressed in MM,
      with higher levels detected in solid tumors, although its expression is more
      limited than in gynecological adenocarcinomas. The presence of hK4 in MM, a non
      hormonally regulated tumor, provides further support to the histogenetic link
      between mesothelial and epithelial cells.

PMID- 17230567
TI  - Secondary prostatic adenocarcinoma: a cytopathological study of 50 cases.
AB  - Positive diagnosis of metastatic prostate adenocarcinoma (PAC) can be made by
      microscopic examination of the cytologic specimens and immunostaining for
      prostate-specific antigen (PSA) and prostate acid phosphatase (PAP).
      Immunohistochemical markers have been known to display negative, weak, or focal
      staining in poorly differentiated PAC and in patients with prior hormonal and/or
      radiation therapy. The purpose of this study is to characterize the cytopathology
      of metastatic PAC as it has not been documented in large series. Fifty cases of
      metastatic PAC with cytological specimens consisting of 41 fine-needle aspiration
      biopsies (FNAB), 6 pleural fluid aspirates, and 3 catheterized urine samples were
      reviewed and correlated with the surgical specimens and the clinical charts.
      Immunostaining for PSA, PAP, cytokeratin AE1/3, cytokeratin 7 (CK7), cytokeratin
      20 (CK20), vimentin, and carcinoembryonic antigen (CEA) was done. Mean patient
      age was 77 +/- 8 yr; serum PSA, 4.1 +/- 2.3; and primary PAC Gleason score, 8.1
      +/- 1.5. Cytologically, the specimens consisted of cell clusters or cell sheets
      with overlapping uniform hyperchromatic nuclei with or without nucleoli. Twelve
      cases were not reactive to PSA and PAP and 44 cases displayed negative
      immunoreactivity to both CK7 and CK20. Carcinoid-like lesions and small cell
      carcinomas were seen in 4 cases and were misdiagnosed as nonprostatic origin
      based on the following features: negative immunoreactivity to PSA and PAP with or
      without positive reactivity to CEA, and different histopathological features when
      compared with the primary PAC. In addition to the frequency of high-grade PAC,
      awareness of the negative immunoreactivity to PSA and PAP, the discrepancy in the
      histopathological patterns between the primary and secondary tumors, especially
      the frequent neuroendocrine differentiation, are helpful features for the
      diagnosis of metastases of prostatic origin.

PMID- 17230568
TI  - Cytology of anaplastic giant cell carcinoma of the thyroid with osteoclast-like
      giant cells--a case report.
AB  - Anaplastic carcinoma of the thyroid is known for its highly aggressive behaviour
      and rapid spread. While the giant cell variant is a well recognized morphologic
      pattern, the presence of osteoclast-like giant cells is a rare occurrence. We
      report a case of anaplastic carcinoma of the thyroid with focal presence of
      osteoclast-like giant cells occurring in an elderly male patient, diagnosed on
      aspiration cytology.

PMID- 17230569
TI  - Fine-needle aspiration cytologic diagnosis of metastatic melanotic schwannoma:
      familial case of a mother and daughter with Carney's complex and literature
      review.
AB  - Carney's complex is an autosomal dominant, multisystem tumorous disorder that
      includes myxomas, spotty skin pigmentation, endocrine tumors, and peripheral
      nerve tumors. Psammomatous melanotic schwannomas have recently been included as a
      part of this complex. Here, we describe the first known familial case of a mother
      and daughter, both presenting with malignant, already metastatic, pigmented
      schwannomas initially diagnosed as metastatic melanoma by CT guided fine-needle
      aspiration. Patients with highly pigmented, extra-cutaneous lesions that are
      clinically and pathologically suspicious for metastatic malignant melanoma,
      without known primary tumor, should be evaluated for possible Carney's complex.
      Additional screening of family members should be recommended to exclude the
      presence of potentially malignant neoplasms, such as psammomatous melanotic
      schwannomas.

PMID- 17230570
TI  - Fine-needle aspiration biopsy of monophasic variant of spindle epithelial tumor
      with thymus-like differentiation of the thyroid: report of one case and review of
      the literature.
AB  - Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare
      biphasic tumor of the thyroid with approximately 20 well-documented cases
      reported in the English literature. Although a monophasic variant of SETTLE is
      conceivable, the majority of the reported cases were truly biphasic tumors. A
      minimal amount of epithelial component was present in the reported cases of so
      called spindle-cell predominant SETTLE. Here, we report an apparently monophasic
      case of SETTLE in a 16-yr-old girl, in which no epithelial cells were identified
      in either fine-needle aspiration biopsy (FNAB) or the subsequent
      hemithyroidectomy specimen. The FNAB smears were moderately cellular and composed
      of single and loosely grouped spindle cells with homogenous metachromatic
      material, which could be mistaken as amyloid, erroneously suggesting medullary
      thyroid carcinoma. The compact nodules of uniform spindle cells in histology
      sections raised the possibility of monophasic synovial sarcoma. The spindle cells
      stained positive for both cytokeratin and vimentin, but were negative for
      thyroglobulin and calcitonin as well as neuroendocrine markers, confirming the
      diagnosis of SETTLE.

PMID- 17230571
TI  - Fine-needle aspiration cytology of basal cell adenoma of the parotid gland:
      characteristic cytological features and diagnostic pitfalls.
AB  - We retrospectively studied the cytological features of aspiration cytology in 12
      cases of basal cell adenoma (BCA) and 5 cases mistakenly diagnosed as BCA. On
      macroscopic findings, the 12 cases of BCA included 7 cases of solid type and 5
      cases of cystic type. The characteristic cytological features of solid type BCA
      were three-dimensional clusters in 71%, sharp-angle small clusters in 86%,
      basement membrane- like material in 71%, and cell crush in 86%. In contrast, 3 of
      the 5 cystic type BCA cases showed inadequate cellular components or no basaloid
      tumor cells, and the cytological diagnosis of BCA could not be determined. In the
      5 cases misdiagnosed as BCA, there were 2 cases of pleomorphic adenoma, 2 cases
      of benign lymphoepithelial cyst, and 1 case of basal cell adenocarcinoma.
      Accurate differential cytological diagnosis of BCA is relatively easy to
      determine the solid type BCA, but is more difficult for cystic type BCA.

PMID- 17230572
TI  - A three-armed trial of the ThinPrep Imaging System.
AB  - We compared the performance of the ThinPrep (TP) Imaging System (TIS) with manual
      reading of TP slides (TPM) and with manual reading of the paired conventional Pap
      smear (PS) in terms of sensitivity for and positive predictive value (PPV) of
      high-grade disease and productivity. The study consisted of 11,416 routine PS and
      paired TP slides as well as 103 confirmed abnormal TP slides. In terms of
      sensitivity for the detection of biopsy-confirmed high-grade disease, overall
      there was no statistically significant difference between TIS-screened TP (TPI)
      and TPM (81.1% vs. 86.8%). For the routine cases, TPI was significantly more
      sensitive than PS (73.4% vs. 57.8%). In terms of PPVs for the cytologic
      prediction of high-grade disease, there was no statistically, significant
      difference among TPI, TPM, and PS (75.6%, 73.9%, and 84.6%). For cytologic
      reports of possible high-grade disease, the PPVs were equivalent for TPI (45.0%)
      and TPM (37.0%) and there was no significant difference in PPVs between TPI and
      PS (61.3%). For TP slides, TIS screening showed a 27% productivity gain when
      compared with manual screening and a 54% productivity gain when compared with
      manual screening of PS slides. Use of TIS showed productivity benefits when
      compared with TPM and both productivity and sensitivity benefits over use of PS.

PMID- 17230573
TI  - Cryptococcal lymphadenitis diagnosed by fine-needle aspiration biopsy.

PMID- 17230574
TI  - Fine-needle aspiration cytology of epidermoid cyst of the thyroid: report of a
      case and review of seven cases.
AB  - The cytological and histological features of a case of epidermoid cyst of thyroid
      are reported. Unlike the more common intrathyroid branchial cleft cyst, this
      lesion does not contain any lymphoid tissue. The presence of scattered small
      groups of smooth muscle fibers in the periepithelial fibrous tissue in this case
      suggests a teratomatous histogenesis.

PMID- 17230575
TI  - Black thyroid.

PMID- 17230576
TI  - Correlation of cytologic examination with ELISA assays for hyaluronan and soluble
      CD44v6 levels in evaluation of effusions.
AB  - Hyaluronan (HA) and its major cell surface receptor, CD44, play an important role
      in tumor growth, proliferation, neovascularization, and invasion. CD44 is an
      integral transmembrane protein and exists in standard form (CD44s), as well as a
      myriad of CD44 variants isoforms (CD44v1-v10). Functional fragments of the CD44
      can be released from the cell membrane by proteolytic cleavage of extracellular
      domain producing soluble CD44. Although studies have proposed the use of serum HA
      and soluble CD44, specifically soluble CD44v6 (sCD44v6) levels, as a tumor
      markers, its diagnostic utility in body fluid samples has not been clearly
      established. The purpose of this study was to correlate HA and sCD44v6 levels in
      effusions with the cytology diagnosis and to assess their usefulness in
      differentiating between malignant and nonmalignant effusions. In this
      retrospective study we evaluated HA and sCD44v6 contents in 20 effusions from
      cytologically positive samples and 10 effusions from cytologically negative
      samples. Corresponding cytopathology slides were reviewed to confirm the
      diagnoses. Malignant effusions included 18 cases of metastatic adenocarcinomas (9
      ovarian, 3 breast, 3 pulmonary, 3 adenocarcinoma of unknown primary) and 2 cases
      of lymphomas. The level of HA and sCD44v6 were measured using a sandwich enzyme
      linked immunoadsorbent assay. For HA, we used hyaluronic acid quantitative test
      kit (Corgenix, Denver, CO) and for sCD44v6 we used Human sCD44v6 Instant ELISA
      (Bender MedSystems, Vienna, Austria). HA concentrations (microg/mL) and sCD44v6
      concentrations (ng/mL) were calculated and correlated with clinical data as well
      as cytodiagnosis. The mean concentration of HA (22.42 +/- 5 microg/mL) and
      sCD44v6 (70 +/- 42 ng/mL) in the cytologically positive samples was significantly
      higher than those in the cytologically negative samples for HA (5.5 +/- 5
      microg/mL, P < 0.01) and sCD44V6 (17 +/- 10 ng/mL, P < 0.01). Using benign
      effusions as control and the upper limits of its mean levels for HA (10.5
      microg/mL) as the positive boundary value, HA levels exceeded the boundary line
      in 17 out of 20 malignant effusions and 2 out of 10 benign effusions. Meanwhile,
      sCD44v6 exceeded the boundary line (27 ng/mL) in 18 out of 20 malignant effusions
      and 3 out of 10 benign effusions. The calculated sensitivity and specificity of
      this assay to the diagnosis of malignant effusions were 85 and 80% for HA and 90
      and 70% for CD44v6, respectively. We conclude that the HA and sCD44v6 levels in
      body fluids correlate with the cytology diagnosis and could be used as an
      ancillary study in cytology to differentiate nonmalignant from malignant
      effusions.

PMID- 17230577
TI  - Cytopathologic findings in an immature cystic teratoma: report of an unusual
      case.
AB  - Teratomas are uncommon, usually benign tumors often found in young women. We
      describe the cytopathology of an unusual case of a large congenital teratoma in a
      6-day-old girl. The patient initially showed signs of abdominal distention and a
      follow-up ultrasound and computerized-tomography (CT) revealed a cystic mass in
      the pelvis. An ultrasound-guided fine-needle aspiration (FNA) showed small round
      blue cells suspicious for a primitive neuronal tumor. Resection of the mass
      displayed a cystic teratoma with distinct nests of small round blue cells
      representing immature neuroepithelial and glial tissue. Also noted were admixed
      mature elements of a cystic teratoma. Cytologic finding of a small round blue
      cell tumor, therefore, was the immature component of the teratoma. This case
      illustrates the difficulties in diagnosing teratomas due to their extraordinary
      diversity.

PMID- 17230578
TI  - Three cases of extranodal NK/T-cell lymphoma of the nasal type diagnosed by nasal
      brush cytology.
AB  - Extranodal natural killer (NK)/T-cell lymphoma of the nasal type is a rare type
      of malignant lymphoma that is most common in Asian countries. Here we describe
      cytomorphologic, immunocytochemical, and molecular cytochemical features of three
      cases of NK/T-cell lymphoma of the nasal type diagnosed by nasal brush cytology.
      Cytomorphologic findings common among the three cases included the presence of
      several cell types, including nasal cavity epithelial cells, histiocytes,
      phagocytic histiocytes, and lymphoid cells, within a necrotic background.
      Suspected lymphoma cells were medium to large lymphoid cells possessing light
      blue and abundant cytoplasm. A characteristic feature of these cells was the
      presence of the tongue-like projections of cytoplasm from one or both sides of
      the cells. We believe these intriguing cytologic findings are indicators of NK/T
      cell lymphoma of the nasal type. Azurophilic granules were observed in all cases,
      ranging from extremely fine granules to large granular lymphocyte (LGL)-like
      granules. Immunocytochemical and molecular cytochemical analyses showed staining
      for natural killer cell antigen CD56 as well as cytotoxic granule-associated
      proteins granzyme B7 (GrB7) and T-cell-restricted intercellular antigen-1 (TIA
      1). EBV (Epstein-Barr virus) encoded small RNAs (EBER) positivity was shown by in
      situ hybridization, and no rearrangement of the TCRgamma gene was observed.
      Comparison between cytobrush and cotton swab methodology showed that cytobrush
      resulted in more cell-rich specimens than did cotton swabs, suggesting that nasal
      brush cytology with cytobrush is most useful in the diagnosis of NK/T-cell
      lymphoma of the nasal type.

PMID- 17230580
TI  - Comparison of sampling techniques for parallel analysis of transcript and
      metabolite levels in Saccharomyces cerevisiae.
AB  - Mathematical modelling of cellular processes is crucial for the understanding of
      the cell or organism as a whole. Genome-wide observations, at the levels of the
      transcriptome, proteome and metabolome, provide a high coverage of the molecular
      constituents of the system in study. Time-course experiments are important for
      gaining insight into a system's dynamics and are needed for mathematical
      modelling. In time-course experiments it is crucial to use efficient and fast
      sampling techniques. We evaluated several techniques to sample and process yeast
      cultures for parallel analysis of the transcriptome and metabolome. The
      evaluation was made by measuring the quality of the RNA obtained with UV
      spectroscopy, capillary electrophoresis and microarray hybridization. The
      protocol developed involves rapid collection by spraying the sample into -40
      degrees C tricine-buffered methanol (as previously described for yeast metabolome
      analysis), followed by the separation of cells from the culture medium in low
      temperature rapid centrifugation. Removal of the residual methanol is carried out
      by freeze-drying the pellet at -35 degrees C. RNA and metabolites can then be
      extracted from the same freeze-dried sample obtained with this procedure.

PMID- 17230581
TI  - The 160 N-terminal residues of calnexin define a novel region supporting
      viability in Schizosaccharomyces pombe.
AB  - Protein secretion is a complex process that can be modulated by folding factors
      in the endoplasmic reticulum (ER), such as calnexin, a highly-conserved molecular
      chaperone involved in quality control. In Schizosaccharomyces pombe, calnexin
      (Cnx1p) is essential for cell viability. The calnexin/Cnx1p determinants required
      for viability have been mapped within the last 123 residues of its C-terminus. To
      better understand the role(s) of calnexin/Cnx1p in secretion, we screened for
      cnx1 mutants 'super-secreting' cellulase. We identified ss14_cnx1, a mutant
      secreting 10-fold higher levels of the glycoprotein cellulase than the wild-type
      strain. While cellulase did not interact with ss14_Cnx1p, the ratio of secreted
      activity/quantity for this enzyme was not affected, suggesting that the quality
      control of folding in the ER was adequate in the mutant strain. Surprisingly, the
      ss14_Cnx1p mutant is composed of the 160 N-terminal amino acids of the mature
      molecule, thus this mutant defines a novel calnexin/Cnx1p region supporting Sz.
      pombe viability. Interestingly, like viable mutants spanning the last 52 aa of
      calnexin/Cnx1p, the 160 N-terminal residues encoded by ss14_cnx1 also forms a
      complex with the essential BiP chaperone. These results reveal the so far
      unidentified importance of the N-terminal region of calnexin/Cnx1p.

PMID- 17230583
TI  - Mass spectrometric identification of covalently bound cell wall proteins from the
      fission yeast Schizosaccharomyces pombe.
AB  - The cell wall of Schizosaccharomyces pombe is bilayered, consisting of an inner
      layer of mainly polysaccharides and an outer layer of galactomannoproteins. We
      present a detailed analysis of the cell wall proteome. Six covalently-bound cell
      wall proteins (CWPs) were identified using tandem mass spectrometry, including
      four predicted GPI-dependent CWPs (Gas1p, Gas5p, Ecm33p and Pwp1p) and two alkali
      sensitive CWPs (Psu1p and Asl1p). Gas1p and Gas5p belong to glycoside hydrolase
      family 72, and are believed to be involved in 1,3-beta-glucan elongation. Ecm33p
      belongs to a ubiquitous fungal protein family with an unknown but crucial
      function in cell wall integrity. Pwp1p is an abundant protein with an unknown but
      probably non-enzymatic function. All four CWPs were present in HF-pyridine
      extracts, indicating that they are linked via a phosphodiester bridge to the
      glucan network. Psu1p is a homologue of the Saccharomyces cerevisiae Sun family,
      whereas Asl1p has no homologues in S. cerevisiae but is related to Aspergillus
      fumigatus and Ustilago maydis proteins. Finally, although the protein content of
      Sz. pombe cell walls is only slightly less than in S. cerevisiae and Candida
      albicans, the amount of carbohydrate added to the proteins was found to be two-
      to three-fold decreased, consistent with earlier reported differences in outer
      chain N-glycosylation.

PMID- 17230582
TI  - Towards a nanoscale view of fungal surfaces.
AB  - In the past years, atomic force microscopy (AFM) has offered novel possibilities
      for exploring the nanoscale surface properties of fungal cells. For the first
      time, AFM imaging enables investigators to visualize fine surface structures,
      such as rodlets, directly on native hydrated cells. Moreover, real-time imaging
      can be used to follow cell surface dynamics during cell growth and to monitor the
      effect of molecules such as enzymes and drugs. In fact, AFM is much more than a
      microscope in that when used in the force spectroscopy mode, it allows
      measurement of physicochemical properties such as surface energy and surface
      charge, to probe the elasticity of cell wall components and macromolecules, and
      to analyse the force and localization of molecular recognition events.

PMID- 17230586
TI  - Acrylamide levels in Finnish foodstuffs analysed with liquid chromatography
      tandem mass spectrometry.
AB  - Sample clean-up and HPLC with tandem mass spectrometric detection (LC-MS/MS) was
      validated for the routine analysis of acrylamide in various foodstuffs. The
      method used proved to be reliable and the detection limit for routine monitoring
      was sensitive enough for foods and drinks (38 microg/kg for foods and 5 microg/L
      for drinks). The RSDs for repeatability and day-to-day variation were below 15%
      in all food matrices. Two hundred and one samples which included more than 30
      different types of food and foods manufactured and prepared in various ways were
      analysed. The main types of food analysed were potato and cereal-based foods,
      processed foods (pizza, minced beef meat, meat balls, chicken nuggets, potato-ham
      casserole and fried bacon) and coffee. Acrylamide was detected at levels, ranging
      from nondetectable to 1480 microg/kg level in solid food, with crisp bread
      exhibiting the highest levels. In drinks, the highest value (29 microg/L) was
      found in regular coffee drinks.

PMID- 17230587
TI  - Dose-response feeding study of short chain chlorinated paraffins (SCCPs) in
      laying hens: effects on laying performance and tissue distribution, accumulation
      and elimination kinetics.
AB  - Technical short chain chlorinated paraffins (C10-C13 with 60% chlorine) were fed
      to 93 laying hens from 24 to 32 weeks of age in increasing concentrations of up
      to 100 mg/kg feed. No significant influence on health, relative organ weights or
      performance (laying intensity, egg weight, feed consumption) was noted. The
      chlorinated paraffin content of the tissues was linearly related to the
      concentration of short chain paraffins of the feed. The highest concentrations
      were found in abdominal fat, egg yolk and fatty tissues. Breast muscle, egg
      albumen and bile fluid contained minimal or no residues. Less than 1% of the
      chlorinated paraffins ingested were incorporated into the body (without head,
      feet, gut and feathers), whereas about 1.5% were eliminated with the egg yolk and
      30% were excreted with urine and faeces. A six-week kinetic depuration study
      revealed a biphasic elimination with half-lifes of 4-40 min (liver, kidneys,
      legs, fat, blood) for the initial rapid phase, and 15-30 days (blood, fat, liver,
      yolk, kidneys, legs) for the terminal slow phase.

PMID- 17230584
TI  - Impact of copper on the induction and repair of oxidative DNA damage, poly(ADP
      ribosyl)ation and PARP-1 activity.
AB  - Copper is an essential trace element involved, among other functions, in
      enzymatic antioxidative defense systems. However, nonprotein bound copper ions
      have been shown to generate reactive oxygen species. To gain insight into the
      discrepancy between the protective properties of copper on the one hand and its
      toxicity on the other hand, we examined the genotoxic effects of CuSO(4) in
      cultured human cells. Here we report that copper, at cytotoxic concentrations,
      induces oxidative DNA base modifications and DNA strand breaks. However, at lower
      noncytotoxic concentrations, copper inhibits the repair of oxidative DNA damage
      induced by visible light. As a first mechanistic hint, inhibition of H(2)O(2)
      induced poly(ADP-ribosyl)ation was identified in cultured cells and further
      experiments demonstrated a strong inhibition of the activity of isolated poly(ADP
      ribose)polymerase-1 (PARP-1) by copper. Bioavailability studies of copper showed
      a dose-dependent uptake in cells and pointed out the relevance of the applied
      concentrations. Taken together, the results indicate that copper, under
      conditions of either disturbed homeostasis or overload due to high exposure,
      exerts defined genotoxic effects. Hence, a balance needs to be maintained to
      ensure sufficient uptake and to prevent overload.

PMID- 17230589
TI  - Interface Fermi level pinning at contacts between PEDOT: PSS and molecular
      organic semiconductors.
AB  - Photoemission studies of interfaces between molecular organic semiconductors and
      the conducting polymer PEDOT:PSS [mixture of PEDOT (poly-3,4-ethylenedioxy
      thiophene) and PSS (polystyrenesulfonate)] demonstrate that it is impossible to
      control the charge injection barriers at such contacts by either a systematic
      change of the work function of the conducting polymer or that of the organic
      semiconductor. Instead, these interfaces are, in all cases, characterized by a
      charge transfer across the interface and a resulting Fermi level pinning. Thus
      interfacial charge barriers do not explain observed changes in device parameters
      as a function of the work function of the polymer electrode.

PMID- 17230591
TI  - Self-organized TiO2 nanotube layers as highly efficient photocatalysts.

PMID- 17230588
TI  - The epidermal growth factor receptor and human topoisomerases represent potential
      cellular targets of oligomeric procyanidins.
AB  - Oligomeric procyanidins were found to inhibit the protein tyrosine kinase
      activity of the epidermal growth factor receptor (EGFR). The inhibitory potency
      was found to increase with the degree of oligomerisation (PA2 > PC1 >> PB1 = PB2
      = PB3 = PB4 >> (-)-epicatechin). To address the question whether the interference
      with the activity of isolated EGFR preparations also plays a role within intact
      cells, effects on the phosphorylation status of the EGFR, as a measure of its
      activity, were determined in human colon carcinoma cells. Treatment of HT29 cells
      with the trimeric procyanidin PC1 resulted in a decrease of the EGFR
      autophosphorylation already at low micromolar concentrations. A respective
      procyanidin tetramer (PA2) failed to affect substantially the receptor
      phosphorylation status by up to 50 microM, indicating that the effectiveness of
      oligomeric procyanidins against EGFR activity within intact cells might be
      limited with increasing degree of polymerisation. Nevertheless, oligomeric
      procyanidins were identified as potential inhibitors of the EGFR, which might be
      of interest with respect to chemoprevention. However, PC1 and PA2 were also
      identified as potent inhibitors of the catalytic activity of human topoisomerase
      I and II, demanding further studies to elucidate whether the interference of
      procyanidins with topoisomerases might impair DNA integrity, thus limiting their
      usefulness in terms of chemoprevention.

PMID- 17230585
TI  - Fecal water from ileostomic patients consuming oat beta-glucan enhances immune
      responses in enterocytes.
AB  - Yeast, fungal, and dietary beta-glucans have immune-modulating effects in vitro
      and in vivo, as thought, mainly by affecting leukocytes; however, effects of oat
      beta-glucan on enterocytes have never been studied. As recognized, supplying oat
      beta-glucans as such to cells in culture directly is difficult because of
      solubility problems. Therefore, six ileostomic patients consumed, in random
      order, a control diet or an oat beta-glucan enriched diet (5 g) and from the
      collected ileostomic content, fecal water was prepared and added to two small
      intestinal cell lines (INT407, Caco-2) and two colon cell lines (HT29, T84)
      together with a cytokine cocktail (IL-1beta + INFgamma + TNFalpha). Several
      parameters reflecting immune-modulation were measured. As compared to placebo
      fecal water, beta-glucan enriched fecal water significantly increased IL-8
      production in HT29 (5.0%; p = 0.046) and INT407 cells (22.0%; p = 0.028).
      Intercellular adhesion molecule (ICAM)-1 expression increased in T84 (11.0%; p =
      0.028) and Caco-2 cells (20.4%; p = 0.075). These immune-stimulating effects were
      confirmed by enhancement of inflammatory expression profiles, as determined with
      an antibody array. Our findings show immune enhancement by fecal water from
      ileostomic patients consuming oat beta-glucan both in small intestinal and colon
      cell lines after stimulation, which is in agreement with documented effects in
      leukocytes. Whether these immune-stimulating effects on enterocytes contribute to
      the enhanced protection of the host against invading pathogens as observed both
      in animals and in humans, as well as the underlying mechanism, needs further
      evaluation.

PMID- 17230594
TI  - A metalloid [Ga23{N(SiMe3)2}11] cluster: the Jellium model put to test.

PMID- 17230593
TI  - [Au3Ge18](5-)--a gold-germanium cluster with remarkable Au-Au interactions.

PMID- 17230590
TI  - Facile aqueous-phase synthesis of uniform palladium nanoparticles of various
      shapes and sizes.

PMID- 17230595
TI  - Selective dimetalation of [Mn(eta5-C5H5)(eta6-C6H6)]: crystal structure and
      conversion to strained [n]metalloarenophanes.

PMID- 17230596
TI  - Oral-intravenous crossover study of fingolimod pharmacokinetics, lymphocyte
      responses and cardiac effects.
AB  - OBJECTIVE: The pharmacokinetics and lymphocyte responses to the immunomodulator
      fingolimod (FTY720) were characterized after oral and intravenous administration.
      METHODS: In this randomized, two-period crossover study 11 evaluable healthy
      subjects received single doses of fingolimod 1.25 mg orally and 1 mg
      intravenously infused over 2 h. The pharmacokinetics of fingolimod, blood
      lymphocyte counts and heart rate were characterized for 28 days after each dose.
      RESULTS: After oral administration, Cmax was 1.1+/-0.2 ng/ml occurring at 12 h
      postdose and the AUC was 201+/-31 ng.h/ml. After intravenous infusion, Cmax was
      4.9+/-0.8 ng/ml, AUC was 175+/-50 ng. h/ml, clearance was 6.3+/-2.3 l/h and
      distribution volume was 1199+/-260 l. The oral/intravenous ratio of dose
      normalized AUCs was 0.94 (95%CI: 0.78-1.12). The pharmacologically active
      metabolite fingolimod-phosphate was quantifiable near its peak after oral
      administration but not after intravenous administration. The mean lymphocyte
      nadir occurred on day 1 and was 35% lower after oral (0.74x10(9)/l) than after
      intravenous (1.15x10(9)/l) administration. Lymphocytes recovered to the normal
      range by day 15 for both treatments. The mean heart rate nadir occurred 3-4 h
      postdose and was 11% lower after oral administration (47 bpm) versus intravenous
      administration (53 bpm). CONCLUSIONS: Average systemic exposure to fingolimod was
      similar after oral and intravenous administration. However, the acute decrease in
      lymphocyte counts was weaker after intravenous administration, likely because of
      lower blood levels of the active metabolite fingolimod-phosphate compared with
      oral administration.

PMID- 17230597
TI  - Pharmacokinetics of 5-fluorouracil in mutant Nagase analbuminemic rats: faster
      metabolism of 5-fluorouracil via CYP1A.
AB  - It has been reported that plasma albumin concentrations were significantly lower
      in cancer patients than those in the healthy volunteers, and the expression and
      mRNA level of hepatic microsomal cytochrome P450 (CYP) 1A2 increased in mutant
      Nagase analbuminemic rats (NARs). After intravenous administration of 5
      fluorouracil at a dose of 30 mg/kg to NARs, the time-averaged nonrenal clearance
      (Clnr) of the drug was significantly faster than the controls (51.3 versus 28.8
      ml/min/kg), possibly due to an increase in the expression and mRNA level of
      CYP1A2 in NARs. In order to determine whether 5-fluorouracil is metabolized via
      CYP1A2 in male Sprague-Dawley rats, the rats were pretreated with 3
      methylcholanthrene (a main inducer of CYP1A1/2 in rats). The Clnr of 5
      fluorouracil was significantly faster (34.3 versus 27.3 ml/min/kg) in rats
      pretreated with 3-methylcholanthrene. The aforementioned data indicate that CYP1A
      is involved in the metabolism of 5-fluorouracil in rats.

PMID- 17230598
TI  - Disposition of abouthiouzine: a novel antihyperthyroid drug.
AB  - Abouthiouzine is a novel antithyroid agent with a profile of fewer reported
      adverse effects than other currently used drugs. The purpose of this current work
      was to explore, for the first time, the disposition of abouthiouzine following
      intravenous and oral administration using an animal model; also, to study its
      plasma protein binding properties. Abouthiouzine (2 mg/kg intravenously) was
      administered to healthy male Vole rabbits and Beagle dogs. A dose of 20 mg/kg of
      the drug was also given orally to another group of Beagle dogs. Abouthiouzine
      plasma concentrations were measured using an HPLC method, and its pharmacokinetic
      parameters were determined by non-compartmental analysis. Abouthiouzine plasma
      protein binding was determined using an ultrafiltration technique. The drug was
      quickly eliminated from the rabbit and dog systemic circulations with terminal
      half-lives (T(1/2 lambda)) of 0.7 h and 1.9 h, respectively. The calculated T(1/2
      lambda) following the oral administration in dogs was 1.8 h. Total abouthiouzine
      clearance (CL) in rabbits was 7.84+/-0.87 ml/min/kg, and 4.03+/-0.83 ml/min/kg in
      dogs. The apparent volume of distribution at steady state (V(ss)) in rabbits and
      dogs was 360.09+/-63.41 ml/kg and 481.10+/-62.64 ml/kg, respectively. The
      absolute oral bioavailability in dogs was approximately 16%, which may indicate
      poor absorption characteristics of the pure drug and/or an extensive first past
      effect. Protein binding studies have demonstrated that abouthiouzine has moderate
      to-high binding properties ( approximately 63%-86%). Further studies are needed
      to evaluate the route of elimination of abouthiouzine in these animal models
      including any metabolite formation and the role of enterohepatic recycling in
      this process.

PMID- 17230600
TI  - Identification of the differential expressive tumor associated genes in rectal
      cancers by cDNA microarray.
AB  - AIM: To identify tumor associated genes of rectal cancer and to probe the
      application possibility of gene expression profiles for the classification of
      tumors. METHODS: Rectal cancer tissues and their paired normal mucosa were
      obtained from patients undergoing surgical resection of rectal cancer. Total RNA
      was extracted using Trizol reagents. First strand cDNA synthesis was indirectly
      labeled with aminoallyl-dUTP and coupled with Cy3 or Cy5 dye NHS mono-functional
      ester. After normalization to total spots, the genes which background subtracted
      intensity did not exceed 2 SD above the mean blank were excluded. The data were
      then sorted to obtain genes differentially expressed by >or= 2 fold up or down in
      at least 5 of the 21 patients. RESULTS: In the 21 rectal cancer patients, 23
      genes were up-regulated in at least 5 samples and 15 genes were down-regulated in
      at least 5 patients. Hierachical cluster analysis classified the patients into
      two groups according to the clinicopathological stage, with one group being all
      above stage II and one group all below stage II. CONCLUSION: The up-regulated
      genes and down-regulated genes may be molecular markers of rectal cancer. The
      expression profiles can be used for classification of rectal cancer.

PMID- 17230599
TI  - Assessment of drug-induced hepatotoxicity in clinical practice: a challenge for
      gastroenterologists.
AB  - Currently, pharmaceutical preparations are serious contributors to liver disease;
      hepatotoxicity ranking as the most frequent cause for acute liver failure and
      post-commercialization regulatory decisions. The diagnosis of hepatotoxicity
      remains a difficult task because of the lack of reliable markers for use in
      general clinical practice. To incriminate any given drug in an episode of liver
      dysfunction is a step-by-step process that requires a high degree of suspicion,
      compatible chronology, awareness of the drug's hepatotoxic potential, the
      exclusion of alternative causes of liver damage and the ability to detect the
      presence of subtle data that favors a toxic etiology. This process is time
      consuming and the final result is frequently inaccurate. Diagnostic algorithms
      may add consistency to the diagnostic process by translating the suspicion into a
      quantitative score. Such scales are useful since they provide a framework that
      emphasizes the features that merit attention in cases of suspected hepatic
      adverse reaction as well. Current efforts in collecting bona fide cases of drug
      induced hepatotoxicity will make refinements of existing scales feasible. It is
      now relatively easy to accommodate relevant data within the scoring system and to
      delete low-impact items. Efforts should also be directed toward the development
      of an abridged instrument for use in evaluating suspected drug-induced
      hepatotoxicity at the very beginning of the diagnosis and treatment process when
      clinical decisions need to be made. The instrument chosen would enable a
      confident diagnosis to be made on admission of the patient and treatment to be
      fine-tuned as further information is collected.

PMID- 17230602
TI  - Hepatitis C virus genotypes in Serbia and Montenegro: the prevalence and clinical
      significance.
AB  - AIM: To investigate the prevalence of hepatitis C virus (HCV) genotypes in Serbia
      and Montenegro and their influence on some clinical characteristics in patients
      with chronic HCV infection. METHODS: A total of 164 patients was investigated.
      Complete history, route of infection, assessment of alcohol consumption, an
      abdominal ultrasound, standard biochemical tests and liver biopsy were done. Gene
      sequencing of 5' NTR type-specific PCR or commercial kits was performed for HCV
      genotyping and subtyping. The SPSS for Windows (version 10.0) was used for
      univariate regression analysis with further multivariate analysis. RESULTS: The
      genotypes 1, 2, 3, 4, 1b3a and 1b4 were present in 57.9%, 3.7%, 23.2%, 6.7%, 6.7%
      and 1.8% of the patients, respectively. The genotype 1 (mainly the subtype 1b)
      was found to be independent of age in subjects older than 40 years, high viral
      load, more severe necro-inflammatory activity, advanced stage of fibrosis, and
      absence of intravenous drug abuse. The genotype 3a was associated with
      intravenous drug abuse and the age below 40. Multivariate analysis demonstrated
      age over 40 and intravenous drug abuse as the positive predictive factors for the
      genotypes 1b and 3a, respectively. CONCLUSION: In Serbia and Montenegro, the
      genotypes 1b and 3a predominate in patients with chronic HCV infection. The
      subtype 1b is characteristic of older patients, while the genotype 3a is common
      in drug abusers. Association of the subtype 1b with advanced liver disease,
      higher viral load and histological activity suggests earlier infection with this
      genotype and eventually its increased pathogenicity.

PMID- 17230604
TI  - Expression patterns and action analysis of genes associated with inflammatory
      responses during rat liver regeneration.
AB  - AIM: To study the relationship between inflammatory response and liver
      regeneration (LR) at transcriptional level. METHODS: After partial hepatectomy
      (PH) of rats, the genes associated with inflammatory response were obtained
      according to the databases, and the gene expression changes during LR were
      checked by the Rat Genome 230 2.0 array. RESULTS: Two hundred and thirty-nine
      genes were associated with liver regeneration. The initial and total expressing
      gene numbers found in initiation phase (0.5-4 h after PH), G(0)/G(0) transition
      (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and
      structure-function reconstruction (66-168 h after PH) of liver regeneration were
      107, 34, 126, 6 and 107, 92, 233, 145 respectively, showing that the associated
      genes were mainly triggered at the beginning of liver regeneration, and worked at
      different phases. According to their expression similarity, these genes were
      classified into 5 groups: only up-regulated, predominantly up-, only down-,
      predominantly down-, up- and down-, involving 92, 25, 77, 14 and 31 genes,
      respectively. The total times of their up- and down-regulated expression were 975
      and 494, respectively, demonstrating that the expressions of the majority of
      genes were increased, and that of a few genes were decreased. Their time
      relevance was classified into 13 groups, showing that the cellular physiological
      and biochemical activities were staggered during liver regeneration. According to
      gene expression patterns, they were classified into 33 types, suggesting that the
      activities were diverse and complex during liver regeneration. CONCLUSION:
      Inflammatory response is closely associated with liver regeneration, in which 239
      LR-associated genes play an important role.

PMID- 17230601
TI  - Red wine and green tea reduce H pylori- or VacA-induced gastritis in a mouse
      model.
AB  - AIM: To investigate whether red wine and green tea could exert anti-H pylori or
      anti-VacA activity in vivo in a mouse model of experimental infection. METHODS:
      Ethanol-free red wine and green tea concentrates were administered orally as a
      mixture of the two beverages to H pylori infected mice, or separately to VacA
      treated mice. Gastric colonization and gastric inflammation were quantified by
      microbiological, histopathological, and immunohistochemical analyses. RESULTS: In
      H pylori-infected mice, the red wine and green tea mixture significantly
      prevented gastritis and limited the localization of bacteria and VacA to the
      surface of the gastric epithelium. Similarly, both beverages significantly
      prevented gastric epithelium damage in VacA-treated mice; green tea, but not red
      wine, also altered the VacA localization in the gastric epithelium. CONCLUSION:
      Red wine and green tea are able to prevent H pylori-induced gastric epithelium
      damage, possibly involving VacA inhibition. This observation supports the
      possible relevance of diet on the pathological outcome of H pylori infection.

PMID- 17230603
TI  - Monounsaturated fat decreases hepatic lipid content in non-alcoholic fatty liver
      disease in rats.
AB  - AIM: To evaluate the effects of different types of dietary fats on the hepatic
      lipid content and oxidative stress parameters in rat liver with experimental non
      alcoholic fatty liver disease (NAFLD). METHODS: A total of 32 Sprague-Dawley rats
      were randomly divided into five groups. The rats in the control group (n = 8)
      were on chow diet (Group 1), rats (n = 6) on methionine choline-deficient diet
      (MCDD) (Group 2), rats (n = 6) on MCDD enriched with olive oil (Group 3), rats (n
      = 6) on MCDD with fish oil (Group 4) and rats (n = 6) on MCDD with butter fat
      (Group 5). After 2 mo, blood and liver sections were examined for lipids
      composition and oxidative stress parameters. RESULTS: The liver weight/rat weight
      ratio increased in all treatment groups as compared with the control group.
      Severe fatty liver was seen in MCDD + fish oil and in MCDD + butter fat groups,
      but not in MCDD and MCDD + olive oil groups. The increase in hepatic
      triglycerides (TG) levels was blunted by 30% in MCDD + olive oil group (0.59 +/-
      0.09) compared with MCDD group (0.85 +/- 0.04, P < 0.004), by 37% compared with
      MCDD + fish oil group (0.95 +/- 0.07, P < 0.001), and by 33% compared with MCDD +
      butter group (0.09 +/- 0.1, P < 0.01). The increase in serum TG was lowered by
      10% in MCDD + olive oil group (0.9 +/- 0.07) compared with MCDD group (1.05 +/-
      0.06). Hepatic cholesterol increased by 15-fold in MCDD group [(0.08 +/- 0.02,
      this increment was blunted by 21% in MCDD + fish oil group (0.09 +/- 0.02)]. In
      comparison with the control group, ratio of long-chain polyunsaturated fatty
      acids omega-6/omega-3 increased in MCDD + olive oil, MCDD + fish oil and MCDD +
      butter fat groups by 345-, 30- and 397-fold, respectively. In comparison to MCDD
      group (1.58 +/- 0.08), hepatic MDA contents in MCDD + olive oil (3.3 +/- 0.6),
      MCDD + fish oil (3.0 +/- 0.4), and MCDD + butter group (2.9 +/- 0.36) were
      increased by 108%, 91% and 87%, respectively (P < 0.004). Hepatic paraoxonase
      activity decreased significantly in all treatment groups, mostly with MCDD +
      olive oil group (-68%). CONCLUSION: Olive oil decreases the accumulation of
      triglyceride in the liver of rats with NAFLD, but does not provide the greatest
      antioxidant activity.

PMID- 17230605
TI  - Effect of emodin on pancreatic fibrosis in rats.
AB  - AIM: To establish the rats model of chronic fibrosing pancreatitis and to prove
      the anti-fibrotic effect of emodin in chronic pancreatitis with fibrosis.
      METHODS: Fifty rats were randomly divided into five groups, 10 rats in each
      group. Trinitrobenzene sulfonic acid (TNBS) was infused into the pancreatic duct
      to induce chronic pancreatitis in rats (except for normal group). Emodin-treated
      rats were fed with different doses of emodin (20, 40 and 80 mg/kg body weight)
      for 28 d, while normal group and control group received 0.9% sodium chloride
      solution. Serum levels of hyaluronic acid (HA) and laminin (LN) were determined
      by radioimmunoassay. Histopathological alterations were studied by optical
      microscopy. Expression of collagen was also examined while transforming growth
      factor-beta-1 (TGF-beta(1)) was localized by immunochemistry. RESULTS: In emodin
      treated rats, the serum levels of HA and LN were decreased significantly (HA,
      62.2 +/- 19.3 microg/L vs 112.7 +/- 26.5 microg/L, P < 0.05; LN 44.3 +/- 10.4
      microg/L vs 86.2 +/- 16.5 microg/L, P < 0.05); the degree of fibrosis was
      ameliorated observably; the expression of collagen in pancreatic tissue was
      reduced especially in high-dose emodin-treated group (36% +/- 5% vs 42% +/- 6%, P
      < 0.05); with the increased doses of emodin, the expression of TGF-beta(1) was
      declined, compared with those in control group. CONCLUSION: Emodin has an anti
      fibrotic effect on pancreatic fibrosis in rats. Because of its anti-fibrotic
      effect, it could be a potential herb for the treatment of chronic pancreatitis.

PMID- 17230606
TI  - A specific gene-expression signature quantifies the degree of hepatic fibrosis in
      patients with chronic liver disease.
AB  - AIM: To study a more accurate quantification of hepatic fibrosis which would
      provide clinically useful information for monitoring the progression of chronic
      liver disease. METHODS: Using a cDNA microarray containing over 22000 clones, we
      analyzed the gene-expression profiles of non-cancerous liver in 74 patients who
      underwent hepatic resection. We calculated the ratio of azan-stained: total area,
      and determined the morphologic fibrosis index (MFI), as a mean of 9 section
      images. We used the MFI as a reference standard to evaluate our method for
      assessing liver fibrosis. RESULTS: We identified 39 genes that collectively
      showed a good correlation (r > 0.50) between gene-expression and the severity of
      liver fibrosis. Many of the identified genes were involved in immune responses
      and cell signaling. To quantify the extent of liver fibrosis, we developed a new
      genetic fibrosis index (GFI) based on gene-expression profiling of 4 clones using
      a linear support vector regression analysis. This technique, based on a
      supervised learning analysis, correctly quantified the various degrees of
      fibrosis in both 74 training samples (r = 0.76, 2.2% vs 2.8%, P < 0.0001) and 12
      independent additional test samples (r = 0.75, 9.8% vs 8.6%, P < 0.005). It was
      far better in assessing liver fibrosis than blood markers such as prothrombin
      time (r = -0.53), type IV collagen 7s (r = 0.48), hyaluronic acid (r = 0.41), and
      aspartate aminotransferase to platelets ratio index (APRI) (r = 0.38).
      CONCLUSION: Our cDNA microarray-based strategy may help clinicians to precisely
      and objectively monitor the severity of liver fibrosis.

PMID- 17230607
TI  - Yoga: a tool for improving the quality of life in chronic pancreatitis.
AB  - AIM: To determine the effectiveness of yoga on improving the quality of life in
      patients of chronic pancreatitis. METHODS: The patients were randomized to two
      groups. The control group continued their usual care as directed by their
      physicians. Patients in the yoga group, in addition, received biweekly yoga
      sessions for 12 wk. The patients' demographic and health behaviour variables were
      assessed before and after the yoga programme using Medical Outcomes Short Form
      (SF-36) for quality of life, Profile of Mood States for assessing mood and
      Symptoms of Stress Inventory for measuring stress. RESULTS: A total of 60
      patients were enrolled, with 8 drop-outs. Thirty patients were randomized to the
      yoga group and 30 to the control group. Significant improvements were seen in
      overall quality of life, symptoms of stress, mood changes, alcohol dependence and
      appetite after the 12 wk period apart from the general feeling of well-being and
      desire to continue with the programme in future in the yoga group, while there
      was no difference in the control group. CONCLUSION: Yoga is effective on
      improving the quality of life in patients of chronic pancreatitis.

PMID- 17230608
TI  - Leptin levels in the differential diagnosis between benign and malignant ascites.
AB  - AIM: To evaluate the role of leptin levels in the differential diagnosis of
      ascites. METHODS: Ascitic leptin, TNFalpha and serum leptin levels were measured
      in 77 patients with ascites (35 with malignancies, 30 cirrhosis and 12
      tuberculosis). Control serum samples were obtained from 20 healthy subjects.
      Leptin and TNFalpha levels were measured by ELISA. Body mass index (BMI) and
      percentage of body fat (BFM) by skin fold measurement were calculated for all
      patients and control groups. Peritoneal biopsy, ascites cytology and cultures or
      biochemical values were used for the diagnosis of patients. RESULTS: In patients
      with malignancies, the mean serum and ascites leptin levels and their ratios were
      significantly decreased compared to the other patient groups and controls. In
      tuberculosis peritonitis, ascitic fluid TNFalpha levels were significantly higher
      than malignant ascites and cirrhotic sterile ascites. BMI and BFM values did not
      distinguish between patients and controls. CONCLUSION: In patients with malignant
      ascites, levels of leptin and TNFalpha were significantly lower than in patients
      with tuberculous ascites.

PMID- 17230609
TI  - Environmental noise alters gastric myoelectrical activity: Effect of age.
AB  - AIM: To evaluate the effect of age and acoustic stress on gastric myoelectrical
      activity (GMA) and autonomic nervous system function. METHODS: Twenty-one male
      subjects (age range 22-71 years, mean 44 years) were recruited and exposed, in
      random order, to three auditory stimuli (Hospital noise, conversation babble and
      traffic noise) after a 20-min baseline. All periods lasted 20 min and were
      interspersed with a 10 min of recovery. GMA was obtained using a Synectics
      Microdigitrapper. Autonomic nerve function was assessed by monitoring blood
      pressure and heart rate using an automatic recording device. RESULTS: Dominant
      power tended to decrease with increase of age (P < 0.05). The overall percentage
      of three cycle per minute (CPM) activity decreased during exposure to hospital
      noise (12.0%, P <0.05), traffic noise (13.9%, P < 0.05), and conversation babble
      (7.1%). The subjects in the younger group (< 50 years) showed a consistent
      reduction in the percentage of 3 CPM activity during hospital noise (22.9%, P <
      0.05), traffic noise (19.0%, P < 0.05), and conversation babble (15.5%). These
      observations were accompanied by a significant increase in bradygastria: hospital
      noise (P < 0.05) and traffic noise (P < 0.05). In contrast, the subjects over 50
      years of age did not exhibit a significant decrease in 3 CPM activity. Regardless
      of age, noise did not alter blood pressure or heart rate. CONCLUSION: GMA changes
      with age. Loud noise can alter GMA, especially in younger individuals. Our data
      indicate that even short-term exposure to noise may alter the contractility of
      the stomach.

PMID- 17230610
TI  - Extrahepatic collaterals and liver damage in embolotherapy for ruptured hepatic
      artery pseudoaneurysm following hepatobiliary pancreatic surgery.
AB  - AIM: To evaluate the effects of extrahepatic collaterals to the liver on liver
      damage and patient outcome after embolotherapy for the ruptured hepatic artery
      pseudoaneurysm following hepatobiliary pancreatic surgery. METHODS: We reviewed 9
      patients who underwent transcatheter arterial embolization (TAE) for the ruptured
      hepatic artery pseudoaneurysm following major hepatobiliary pancreatic surgery
      between June 1992 and April 2006. We paid special attention to the extrahepatic
      arterial collaterals to the liver which may affect post-TAE liver damage and
      patient outcome. RESULTS: The underlying diseases were all malignancies, and the
      surgical procedures included hepatopancreatoduodenectomy in 2 patients, hepatic
      resection with removal of the bile duct in 5, and pancreaticoduodenectomy in 2. A
      total of 11 pseudoaneurysm developed: 4 in the common hepatic artery, 4 in the
      proper hepatic artery, and 3 in the right hepatic artery. Successful hemostasis
      was accomplished with the initial TAE in all patients, except for 1. Extrahepatic
      arterial pathways to the liver, including the right inferior phrenic artery, the
      jejunal branches, and the aberrant left hepatic artery, were identified in 8 of
      the 9 patients after the completion of TAE. The development of collaterals
      depended on the extent of liver mobilization during the hepatic resection, the
      postoperative period, the presence or absence of an aberrant left hepatic artery,
      and the concomitant arterial stenosis adjacent to the pseudoaneurysm. The liver
      tolerated TAE without significant consequences when at least one of the
      collaterals from the inferior phrenic artery or the aberrant left hepatic artery
      was present. One patient, however, with no extrahepatic collaterals died of liver
      failure due to total liver necrosis 9 d after TAE. CONCLUSION: When TAE is
      performed on ruptured hepatic artery pseudoaneurysm, reduced collateral pathways
      to the liver created by the primary surgical procedure and a short postoperative
      interval may lead to an unfavorable outcome.

PMID- 17230611
TI  - Clinical features and prognosis of patients with extrahepatic metastases from
      hepatocellular carcinoma.
AB  - AIM: To assess the clinical features and prognosis of 151 patients with
      extrahepatic metastases from primary hepatocellular carcinoma (HCC), and describe
      the treatment strategy for such patients. METHODS: After the diagnosis of HCC,
      all 995 consecutive HCC patients were followed up at regular intervals and 151
      (15.2%) patients were found to have extrahepatic metastases at the initial
      diagnosis of primary HCC or developed such tumors during the follow-up period. We
      assessed their clinical features, prognosis, and treatment strategies. RESULTS:
      The most frequent site of extrahepatic metastases was the lungs (47%), followed
      by lymph nodes (45%), bones (37%), and adrenal glands (12%). The cumulative
      survival rates after the initial diagnosis of extrahepatic metastases at 6, 12,
      24, and 36 mo were 44.1%, 21.7%, 14.2%, 7.1%, respectively. The median survival
      time was 4.9 mo (range, 0-37 mo). Fourteen patients (11%) died of extrahepatic
      HCC, others died of primary HCC or liver failure. CONCLUSION: The prognosis of
      HCC patients with extrahepatic metastases is poor. With regard to the cause of
      death, many patients would die of intrahepatic HCC and few of extrahepatic
      metastases. Although most of HCC patients with extrahepatic metastases should
      undergo treatment for the primary HCC mainly, treatment of extrahepatic
      metastases in selected HCC patients who have good hepatic reserve, intrahepatic
      tumor stage (T0-T2), and are free of portal venous invasion may improve survival.

PMID- 17230612
TI  - Serum levels of soluble Fas, nitric oxide and cytokines in acute decompensated
      cirrhotic patients.
AB  - AIM: To evaluate plasma levels of nitrite/nitrate (NOx), soluble Fas (sFas)
      antigen, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in
      patients with compensated and acute decompensated cirrhosis and to evaluate
      mediators causing acute decompensation in liver cirrhosis. METHODS: This
      prospective study was conducted in the medical intensive care unit of an academic
      tertiary center. Fifty-five patients with acute decompensation (gastrointestinal
      hemorrhage, encephalopathy, hydropic decompensation) and twenty-five patients
      with compensated liver cirrhosis were included. Blood samples were taken for
      analyses of sFas, Nox, IL-6, TNF-alpha. Liver enzymes and kidney functions were
      also tested. RESULTS: In patients with acute decompensation, plasma sFas levels
      were higher than in non-decompensated patients (15305 +/- 4646 vs 12458 +/- 4322
      pg/mL, P < 0.05). This was also true for the subgroup of patients with alcoholic
      liver cirrhosis (P < 0.05). The other mediators were not different and none of
      the parameters predicted survival, except for ALT (alanine-aminotransferase). In
      patients with portal-hypertension-induced acute hemorrhage, NOx levels were
      significantly lower than in patients with other forms of decompensation (70.8 +/-
      48.3 vs 112.9 +/- 74.9 pg/mL, P < 0.05). When NOx levels were normalized to
      creatinine levels, the difference disappeared. IL-6, TNF-alpha and sFas were not
      different between bleeders and non-bleeders. In decompensated patients sFas, IL-6
      and NOx levels correlated positively with creatinine levels, while IL-6 levels
      were dependent on Child class. CONCLUSION: In acute decompensated cirrhotic
      patients sFas is increased, suggesting a role of apoptosis in this process and
      patients with acute bleeding have lower NOx levels. However, in this acute
      complex clinical situation, kidney function seems to have a predominant influence
      on mediator levels.

PMID- 17230613
TI  - Expression of COX-2, PCNA, Ki-67 and p53 in gastrointestinal stromal tumors and
      its relationship with histopathological parameters.
AB  - AIM: To investigate the expression of Cyclooxygenase-2 (COX-2), proliferating
      cell nuclear antigen (PCNA), Ki-67 and p53 in gastrointestinal stromal tumors
      (GISTs) and its relationship with histopathological parameters. METHODS: Twenty
      five GISTs were examined by light microscopy and immunohistochemistry. c-kit,
      CD34, SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected
      immunohistochemically and the relationship was evaluated among histopathologic
      parameters such as mitotic index (MI), tumor grade, tumor size, COX-2, PCNA, Ki
      67 and p53. RESULTS: COX-2 protein expression was found in 19 of 25 (76%) of the
      tumors, and expression was noted in the cytoplasm of the tumor cells. p53 was
      significantly related to MI and tumor grade but no relationship was found between
      COX-2, proliferation markers and MI, tumor grade and tumor size. CONCLUSION: COX
      2 is expressed in most GISTs and it may play an important role in the
      proliferation and progression of these tumors or a useful marker to identify
      GIST. Although immunohistochemical assessment of p53 can be used for
      distinguishing the risk groups of GISTs, tumor size and mitotic rate should be
      considered at the same time.

PMID- 17230614
TI  - Acute mechanical bowel obstruction: clinical presentation, etiology, management
      and outcome.
AB  - AIM: To identify and analyze the clinical presentation, management and outcome of
      patients with acute mechanical bowel obstruction along with the etiology of
      obstruction and the incidence and causes of bowel ischemia, necrosis, and
      perforation. METHODS: This is a prospective observational study of all adult
      patients admitted with acute mechanical bowel obstruction between 2001 and 2002.
      RESULTS: Of the 150 consecutive patients included in the study, 114 (76%)
      presented with small bowel and 36 (24%) with large bowel obstruction. Absence of
      passage of flatus (90%) and/or feces (80.6%) and abdominal distension (65.3%)
      were the most common symptoms and physical finding, respectively. Adhesions
      (64.8%), incarcerated hernias (14.8%), and large bowel cancer (13.4%) were the
      most frequent causes of obstruction. Eighty-eight patients (58.7%) were treated
      conservatively and 62 (41.3%) were operated (29 on the first day). Bowel ischemia
      was found in 21 cases (14%), necrosis in 14 (9.3%), and perforation in 8 (5.3%).
      Hernias, large bowel cancer, and adhesions were the most frequent causes of bowel
      ischemia (57.2%, 19.1%, 14.3%), necrosis (42.8%, 21.4%, 21.4%), and perforation
      (50%, 25%, 25%). A significantly higher risk of strangulation was noticed in
      incarcerated hernias than all the other obstruction causes. CONCLUSION: Absence
      of passage of flatus and/or feces and abdominal distension are the most common
      symptoms and physical finding of patients with acute mechanical bowel
      obstruction, respectively. Adhesions, hernias, and large bowel cancer are the
      most common causes of obstruction, as well as of bowel ischemia, necrosis, and
      perforation. Although an important proportion of these patients can be
      nonoperatively treated, a substantial portion requires immediate operation. Great
      caution should be taken for the treatment of these patients since the incidence
      of bowel ischemia, necrosis, and perforation is significantly high.

PMID- 17230615
TI  - Depression and anxiety levels in therapy-naive patients with inflammatory bowel
      disease and cancer of the colon.
AB  - AIM: To assess whether depression and anxiety are more expressed in patients with
      the first episode of inflammatory bowel disease (IBD) than in individuals with
      newly discovered cancer of the colon (CCa). METHODS: A total of 32 patients with
      IBD including 13 males and 19 females, aged 27 to 74, and 30 patients with CCa
      including 20 males and 10 females, aged 39-78, underwent a structured interview,
      which comprised Hamilton's Depression Rating Inventory, Hamilton's Anxiety Rating
      Inventory and Paykel's Stressful Events Rating Scale. RESULTS: Patients of the
      IBD group expressed both depression and anxiety. Depressive mood, sense of guilt,
      psychomotor retardation and somatic anxiety were also more pronounced in IBD
      patients. The discriminant function analysis revealed the total depressive score
      was of high importance for the classification of a newly diagnosed patient into
      one of the groups. CONCLUSION: Newly diagnosed patients with IBD have higher
      levels of depression and anxiety. Moreover, a psychiatrist in the treatment team
      is advisable from the beginning.

PMID- 17230616
TI  - Premedication with pronase or N-acetylcysteine improves visibility during
      gastroendoscopy: an endoscopist-blinded, prospective, randomized study.
AB  - AIM: To assess the efficacy of premedicaton with pronase or N-acetylcysteine
      (NAC) at 20 min before upper gastrointestinal (UGI) endoscopy and to determine
      whether pronase or NAC pretreatment influences the reliability of the rapid
      urease test. METHODS: A total of 146 patients were prospectively and randomly
      assigned into the study groups according to different premedications before
      endoscopy. One endoscopist assessed mucosal visibility (MV) with scores ranged
      from 1 to 4 at four sites in the stomach. The sum of the MV scores from these
      four locations was defined as the total mucosal visibility (TMV) score.
      Identification of H pylori was performed using CLO test, histology, and serology.
      RESULTS: The Group with pronase premedication had a significantly lower TMV score
      than did the groups with gascon and gascon water (P < 0.001 and P < 0.01,
      respectively). The group with NAC had a significantly lower TMV score than the
      group with gascon (P < 0.01) and a trend of a lower MV score than the group with
      gascon water (P = 0.06). The TMV score did not significantly differ between the
      group with pronase and the group with NAC (P = 0.39 and P = 0.14, respectively).
      The sensitivity and specificity of the CLO test were 92.5% and 93.9%,
      respectively, in groups premedicated with pronase and NAC together. CONCLUSION:
      Premedication with pronase or NAC at 20 min before UGI endoscopy improves the
      mucosal visibility of the stomach. Neither pronase nor NAC produces any obvious
      interference with the CLO test for the identification of H pylori infection.

PMID- 17230617
TI  - Liu-stain quick cytodiagnosis of ultrasound-guided fine needle aspiration in
      diagnosis of liver tumors.
AB  - AIM: To combine ultrasound-guided fine-needle aspiration (US-FNA) and Liu (Riu)
      stain to make a quick study on liver tumor lesions. METHODS: Two hundred and
      twenty-eight aspirations from 232 patients were completely studied. The operator
      himself made the quick cytodiagnosis of US-FNA smear stained by Liu method within
      thirty minutes. The US-FNA specimen was also sent to the pathological department
      for cytological study and cellblock histology. The result of our Liu-stain quick
      cytodiagnosis in each patient was confirmed by the final cytopathological
      diagnosis from pathological report. RESULTS: Among 228 samples, the quick
      cytodiagnosis revealed 146 malignancies, 81 benign lesions and one inadequate
      specimen. Cytopathological diagnosis from the pathological department revealed
      150 malignancies, and 78 benign lesions. Four well-differentiated hepatocellular
      carcinomas (HCCs) were under-diagnosed by quick cytodiagnosis as benign and 3
      benign lesions were over-diagnosed as well-differentiated HCCs. Compared with
      cytopathological diagnosis, quick cytodiagnosis correctly diagnosed 143
      malignancies and 77 benign lesions. Except for the one inadequate specimen in
      quick cytodiagnosis, the accuracy of quick cytodiagnosis was 96.9% (220/227), and
      its sensitivity, specificity and positive and negative predictive values were
      97.9%, 95.1%, 97.3% and 96.3%, respectively. CONCLUSION: Liu-stain quick
      cytodiagnosis is a fast, convenient, safe and effective method for hepatologists
      in clinic practice to diagnose liver tumor. In few cases of well-differentiated
      HCC, Liu-stain quick cytodiagnosis has its limitation.

PMID- 17230618
TI  - Short-term application of low-dose growth hormone in surgical patients: effects
      on nitrogen balance and blood glucose.
AB  - AIM: To investigate the effectiveness and safety of recombinant human growth
      hormone (rhGH) in postoperative patients. METHODS: A total of 48 consecutive
      patients undergoing abdominal operations were randomized to receive either
      subcutaneous rhGH (0.15 IU/kg) or placebo (menstruum) injections daily for 7 d
      after surgery. The two groups had similar nutritional intake. Blood samples for
      serum fibronectin, albumin, prealbumin, transferrin and the total lymphocyte
      count, as well as glucose levels were collected to study the rhGH effect. Basal
      laboratory evaluation, and nutritional status were estimated on d 1 before as
      baseline and d 3 and 10 after operation using standard laboratory techniques.
      Nitrogen balance was measured from d 3 to 9 after operation. RESULTS: The
      cumulative nitrogen balance was significantly improved in rhGH group compared
      with the placebo group (11.37 +/- 16.82 vs -9.11 +/- 17.52, P = 0.0003). Serum
      fibronectin was also significantly higher in the rhGH group than in the placebo
      group (104.77 +/- 19.94 vs 93.03 +/- 16.03, P < 0.05), whereas changes in serum
      albumin, prealbumin, transferrin and total lymphocyte counts were not
      statistically significant. Mean blood glucose levels were significantly higher in
      the rhGH group from d 3 to 6 after operation. CONCLUSION: If blood glucose can be
      controlled, low-dose growth hormone together with hypocaloric nutrition is
      effective on improving positive nitrogen balance and protein conservation and
      safe is in postoperative patients.

PMID- 17230619
TI  - Effect of non-anticoagulant N-desulfated heparin on expression of vascular
      endothelial growth factor, angiogenesis and metastasis of orthotopic implantation
      of human gastric carcinoma.
AB  - AIM: To investigate the effect of N-desulfated heparin on tumor metastasis and
      angiogenesis, and expression of vascular endothelial growth factor (VEGF) of
      orthotopic implantation of human gastric carcinoma in male severe combined immune
      deficiency (SCID) mice. METHODS: Human gastric cancer SGC-7901 cells were
      orthotopically implanted into the stomach of SCID mice. The mice were randomly
      divided into normal saline group and N-desulfated heparin group. One week after
      operation, the mice in N-desulfated heparin group received i.v. injections of N
      desulfated heparin (Shanghai Institute of Cell Biology, Chinese Academy of
      Sciences, 10 mg/kg.d) twice weekly for 3 wk. The mice in normal saline group
      received i.v. injections of normal saline (100 microL) twice weekly for 3 wk. The
      mice were sacrificed six weeks after implantation. Tumor metastasis was evaluated
      histologically for metastasis under microscope. Intratumoral microvessel density
      (MVD) and VEGF expression were evaluated immuohistochemically. VEGF mRNA
      expression in gastric tissue of SCID mice was detected by real time PCR. RESULTS:
      The tumor metastasis rate was 80% in normal saline group and 20% in N-desulfated
      heparin group (P < 0.05). MVD was 8.0 +/- 3.1 in normal saline group and 4.3 +/-
      1.8 in N-desulfated heparin group (P < 0.05). VEGF positive immunostaining was
      found in cytoplasm of cancer cells. The rate of VEGF positive expression was
      higher in normal saline group than in N-desulfated heparin treated group (90% vs
      20%, P < 0.05). VEGF mRNA expression was significantly inhibited by N-desulfated
      heparin and was higher in normal saline group than in N-desulfated heparin group
      (Ct value 19.51 +/- 1.01 vs 22.55 +/- 1.36, P < 0.05). N-desulfated heparin
      significantly inhibited the expression of VEGF mRNA in cancer cells. No bleeding
      occurred in N-desulfated heparin group. CONCLUSION: N-desulfated heparin can
      inhibit metastasis of gastric cancer by suppressing tumor VEGF expression and
      tumor angiogenesis, but has no obvious anticoagulant activity.

PMID- 17230620
TI  - Protective effect and mechanism of stronger neo-minophagen C against fulminant
      hepatic failure.
AB  - AIM: To investigate the protective effect of stronger neo-minophafen C (SNMC) on
      fulminant hepatic failure (FHF) and its underlying mechanism. METHODS: A mouse
      model of FHF was established by intraperitoneal injection of galactosamine (D-Gal
      N) and lipopolysaccharide (LPS). The survival rate, liver function, inflammatory
      factor and liver pathological change were obtained with and without SNMC
      treatment. Hepatocyte survival was estimated by observing the stained
      mitochondria structure with terminal deoxynucleotidyl transferase-mediated
      deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method and
      antibodies against cytochrome C (Cyt-C) and caspase-3. RESULTS: The levels of
      plasma tumor necrosis factor alpha (TNF-alpha), nitric oxide (NO), ET-1,
      interleukin-6 (IL-6), and the degree of hepatic tissue injury were decreased in
      the SNMC-treated groups compared with those in the model group (P < 0.01).
      However, there were no differences after different dosages administered at
      different time points. There was a significant difference in survival rates
      between the SNMC-treated groups and the model group (P < 0.01). The apoptosis
      index was 32.3% at 6 h after a low dose of SNMC, which was considerably decreased
      from 32.3% +/- 4.7% vs 5% +/- 2.83% (P < 0.05) to 5% on d 7. The expression of
      Cyt-C and caspase-3 decreased with the prolongation of therapeutic time. Typical
      hepatocyte apoptosis was obviously ameliorated under electron microscope with the
      prolongation of therapeutic time. CONCLUSION: SNMC can effectively protect liver
      against FHF induced by LPS/D-Gal N. SNMC can prevent hepatocyte apoptosis by
      inhibiting inflammatory reaction and stabilizing mitochondria membrane to
      suppress the release of Cyt-C and sequent activation of caspase-3.

PMID- 17230621
TI  - Rectal angiolipoma diagnosed after surgical resection: a case report.
AB  - Angiolipoma is a common benign tumor with a characteristic vascular component
      that usually occurs in subcutaneous tissue. Although lipomas are frequently
      encountered at colonoscopy as submucosal tumors, angiolipomas are rarely found in
      the gastrointestinal tract including the large intestine. Here we report a 77
      year old Japanese man who underwent transanal resection of a tumor that was
      diagnosed tentatively as a leiomyoma. Histologically, the tumor consisted of
      mature fat cells and blood vessels. Immunohistochemically, the tumor cells were
      negative for c-kit and HMB-45, which are consistently expressed in tumors such as
      gastrointestinal stromal tumor and angiomyolipoma. The tumor was therefore
      diagnosed as an angiolipoma. This is thought to be the first case report of a
      surgically resected angiolipoma of the rectum.

PMID- 17230622
TI  - A case of scirrhous gastric cancer with peritonitis carcinomatosa controlled by
      TS-1 + paclitaxel for 36 mo after diagnosis.
AB  - A 34-year-old female complaining of abdominal fullness was diagnosed as scirrhous
      gastric cancer (type 4') with peritonitis carcinomatosa in July 2002. A combined
      chemotherapy regimen was selected to control massive ascites; TS-1 80 mg/m(2) was
      given orally on d 1-14, 22-35, and paclitaxel 50 mg/m(2) was administered
      intravenously on d 1, 8, 22 and 29. After 2 courses of this regimen, the primary
      tumor was markedly reduced, and ascites completely vanished. Alopecia (grade 1,
      since d 30), leukocytopenia (grade 2, on d 34) and anemia (grade 2, on d 34) were
      the only adverse events throughout the following courses. The chemotherapy was
      effective for 28 mo, and then it was discontinued upon the patientos own request,
      and she survived for 36 mo after diagnosis.

PMID- 17230623
TI  - Diagnosis by endoscopic ultrasound guided fine needle aspiration of tuberculous
      lymphadenitis involving the peripancreatic lymph nodes: a case report.
AB  - Pancreatic tuberculosis is an extremely rare form of extrapulmonary disease. The
      diagnosis preoperatively is difficult because clinical, laboratory and radiologic
      findings are nonspecific. Published data indicate that these lesions mimic cystic
      neoplasms of the pancreas and the confirmation of clinical suspicion could only
      be obtained by an open surgical biopsy. Recently, fine needle aspiration cytology
      has been shown to be a safe, reliable and cost-effective alternative. We report a
      new case of a peripancreatic tuberculosis in a 52 year old woman and review the
      relevant literature, paying special attention to the usefulness of endoscopic
      ultrasound guided-fine needle aspiration in the diagnosis of abdominal
      tuberculosis.

PMID- 17230624
TI  - Pancreatic tuberculosis-abdominal tuberculosis presenting as pancreatic abscesses
      and colonic perforation.
AB  - Isolated pancreatic tuberculosis is an extremely rare condition, more so in an
      immunocompetent individual. Its presentation as pancreatic abscesses with colonic
      perforation has not been reported so far. This condition poses difficulties in
      clinical diagnoses. Herein we report a case who was operated in another hospital
      for pancreatic abscesses, and referred to our institution later when he developed
      fecal peritonitis due to colonic perforation. Re-laparotomy, resection and
      exteriorisation of the colon were done. Acid fast bacilli was seen in the
      histopathological examination of the resected colon. The patient responded
      remarkably to anti-tuberculous therapy and two sittings of debridement. Post
      procedure the patient developed pancreatic fistula, which was managed
      successfully with stenting. Pancreatic tuberculosis should be considered as a
      differential diagnosis when pancreatitis is atypical.

PMID- 17230625
TI  - Chylous ascites secondary to hyperlipidemic pancreatitis with normal serum
      amylase and lipase.
AB  - A 54-year old man with a family history of hyperlipidemia was admitted with a 12
      h history of severe generalized abdominal pain associated with nausea, vomiting
      and abdominal distension. Examination of the abdomen revealed tenderness in the
      periumblical area with shifting dullness. Serum pancreatic amylase was 29 IU/L
      and lipase 44 IU/L, triglyceride 36.28 mmol/L. Ultrasound showed ascites. CT of
      the abdomen with contrast showed inflammatory changes surrounding the pancreas
      consistent with acute pancreatitis. Ultrasound (US) guided abdomen paracentesis
      yielded a milky fluid with high triglyceride content consistent with chylous
      ascites. The patient was kept fasting and intravenous fluid hydration was
      provided. Meperidine was administered for pain relief. On the following days the
      patient's condition improved and he was gradually restarted on a low-fat diet,
      and fat lowering agent (gemfibrozil) was begun, 600 mg twice a day. On d 14,
      abdomen US was repeated and showed fluid free peritoneal cavity. The patient was
      discharged after 18 d of hospitalization with 600 mg gemfibrozil twice a day. At
      the time of discharge, the fasting triglyceride was 4.2 mmol/L. After four weeks
      the patient was seen in the clinic, he was well.

PMID- 17230626
TI  - Spontaneous gastrojejunal fistula is a complication of gastric ulcer.
AB  - Spontaneous gastrojejunal fistula formation is an extremely rare complication of
      gastric ulcer disease. We report a 77-year old woman who presented with diffuse
      abdominal pain, weight loss, malaise, nausea, and occasional dark stools.
      Laboratory tests showed extreme hyposideremic anemia with inflammatory syndrome.
      In addition, biochemical parameters of malnourishment were presented. Upper
      endoscopy revealed the patent esophagus along the full length without any
      pathological changes. Large and deep ulceration with perforation in the small
      intestine was detected in the posterior gastric wall. The small intestine loop
      was reached by endoscope through spontaneously developed gastrojejunal fistula.
      Polytopic biopsies of described ulcerative change were carried out.
      Histopathologically reepithelialized ulcerous zone was seen in the gastric
      mucosa. Also, gastrojejunal fistula was visualized after wide opening of
      hepatogastric and gastrocolic ligament. Jejunal loop 25 cm from ligament of
      Treitz was attached to mesocolon and posterior gastric wall because of ulcer
      penetration. Postoperative course was uneventful. Per oral intake started on the
      4(th) postoperative day, and the patient was discharged on the 8(th)
      postoperative day. In summary, this case indicates that persistent symptoms of
      peptic ulcer disease associated with nutritional disturbances may be caused by
      gastrojejunal fistula.

PMID- 17230627
TI  - Does type of instrument influence colonoscopy performance and sedation practice?

PMID- 17230628
TI  - By the way, doctor. Does post-herpetic neuralgia raise C-reactive protein?

PMID- 17230629
TI  - Report from the 13th Conference on Retroviruses and Opportunistic Infections
      (CROI), February 5-8, 2006, Denver, Colorado.

PMID- 17230630
TI  - Complications and side effects. Crestor tested in PHAs.

PMID- 17230631
TI  - Anti-HIV agents. Study finds PEP not 100% effective in preventing HIV infection.

PMID- 17230632
TI  - 4-year update. CDC rewrites treatment guidelines, pushes for more public
      awareness.

PMID- 17230633
TI  - Exposure. Conviction affirmed for man who exposed others to HIV.

PMID- 17230634
TI  - Treatment. CDC: HIV drugs don't reach most HIV-positive individuals.

PMID- 17230635
TI  - Testing. Man's court-ordered HIV test prohibited on appeal.

PMID- 17230636
TI  - State granted custody of rape victim in need of HIV drugs.

PMID- 17230637
TI  - Prisons. Inmate's HIV medication denial case proceeds in new venue.

PMID- 17230638
TI  - Midkine, a heparin-binding growth factor, is expressed in neural precursor cells
      and promotes their growth.
AB  - Midkine, a heparin-binding growth factor, was found to be expressed in neural
      precursor cells, which consist of neural stem cells and the progenitor cells.
      When embryonic brain cells were allowed to form neurospheres enriched in neural
      precursor cells, numbers were significantly smaller from the midkine-deficient
      brain than from the wild-type brain. Dissociated neurosphere cells yielded nestin
      positive neural precursor cells and differentiated neuronal cells upon culture on
      a substratum. Neural precursor cells from the midkine-deficient brain spread
      poorly and grew less effectively on a substratum coated with poly-l-lysine than
      the cells on midkine-coated substratum. Neural precursor cells from the wild-type
      brain spread and grew well on both the substrata. Differentiation to neurons and
      glia cells was not affected by the absence of midkine. Heparitinase digestion of
      dissociated neurosphere cells resulted in poor growth of neural precursor cells,
      while chondroitinase digestion had no effect. These results indicate that midkine
      is involved in the growth of neural precursor cells and suggest that the
      interaction with heparan sulfate proteoglycans is important in midkine action to
      these cells.

PMID- 17230639
TI  - Mediation of adenylyl cyclase sensitization by PTX-insensitive GalphaoA,
      Galphai1, Galphai2 or Galphai3.
AB  - Chronic activation of mu-opioid receptors, which couple to pertussis toxin
      sensitive Galphai/o proteins to inhibit adenylyl cyclase (AC), leads to a
      compensatory sensitization of AC. Pertussis toxin-insensitive mutations of
      Galphai/o subtypes, in which the pertussis toxin-sensitive cysteine is mutated to
      isoleucine (Galpha ), were used to determine whether each of the Galphai/o
      subtypes is able to mediate sensitization of AC. Galpha , G , G or G were
      individually transiently transfected into C6 glioma cells stably expressing the
      mu-opioid receptor, or transiently co-expressed with the mu-opioid receptor into
      human embryonic kidney (HEK)293T cells. Cells were treated with pertussis toxin
      to uncouple endogenous Galphai/o proteins, followed by acute or chronic treatment
      with the mu-opioid agonist, [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO). Each
      Galphai/o subtype mediated acute DAMGO inhibition of AC and DAMGO-induced
      sensitization of AC. The potency for DAMGO to stimulate sensitization was
      independent of the Galphai/o subtype, but the level of sensitization was
      increased in clones expressing higher levels of Galphai/o subunits. Sensitization
      of AC mediated by a component of fetal bovine serum, which was also dependent on
      the level of functional Galphai/o subunits in the cell, was observed. This serum
      mediated sensitization partially masked mu-opioid-mediated sensitization when
      expressed as percentage overshoot due to an apparent increase in AC activity.

PMID- 17230640
TI  - Spotlight:   Gino Gerosa, MD.

PMID- 17230641
TI  - History of cardiology: the use of bloodletting.

PMID- 17230643
TI  - Genes involved in the pathogenesis of primary open-angle glaucoma: in search of
      the Holy Grail.

PMID- 17230642
TI  - Evidence that quinolinic acid severely impairs energy metabolism through
      activation of NMDA receptors in striatum from developing rats.
AB  - In the present study we investigated the effect of intrastriatal administration
      of 150 nmol quinolinic acid to young rats on critical enzyme activities of energy
      production and transfer, as well as on 14CO2 production from [1-14C]acetate at
      distinct periods after quinolinic acid injection. We observed that quinolinic
      acid injection significantly inhibited complexes II (50%), III (46%) and II-III
      (35%), as well as creatine kinase (27%), but not the activities of complexes I
      and IV and citrate synthase in striatum prepared 12 h after treatment. In
      contrast, no alterations of these enzyme activities were observed 3 or 6 h after
      quinolinic acid administration. 14CO2 production from [1-14C]acetate was also
      significantly inhibited (27%) by quinolinic acid in rat striatum prepared 12 h
      after injection. However, no alterations of these activities were observed in
      striatum homogenates incubated in the presence of 100 microm quinolinic acid .
      Pretreatment with the NMDA receptor antagonist MK-801 and with creatine totally
      prevented all inhibitory effects elicited by quinolinic acid administration. In
      addition, alpha-tocopherol plus ascorbate and the nitric oxide synthase inhibitor
      l-NAME completely abolished the inhibitions provoked by quinolinic acid on
      creatine kinase and complex III. Furthermore, pyruvate pretreatment totally
      blocked the inhibitory effects of quinolinic acid injection on complex II
      activity and partially prevented quinolinic acid-induced creatine kinase
      inhibition. These observations strongly indicate that oxidative phosphorylation,
      the citric acid cycle and cellular energy transfer are compromised by high
      concentrations of quinolinic acid in the striatum of young rats and that these
      inhibitory effects were probably mediated by NMDA stimulation.

PMID- 17230644
TI  - Gene symbol: HMBS. Disease: porphyria, acute intermittent.

PMID- 17230645
TI  - Gene symbol: ATP7B. Disease: Wilson disease.

PMID- 17230646
TI  - Gene symbol: MLH1. Disease: colorectal cancer, non-polyposis.

PMID- 17230647
TI  - Gene symbol: HMBS. Disease: porphyria, acute intermittent.

PMID- 17230648
TI  - Gene symbol: NF1. Disease: neurofibromatosis 1.

PMID- 17230649
TI  - Gene symbol: GLA. Disease: Fabry disease.

PMID- 17230650
TI  - Gene symbol: ATP7B. Disease: Wilson disease.

PMID- 17230651
TI  - Gene symbol: AR. Disease: androgen insensitivity syndrome.

PMID- 17230652
TI  - Gene symbol: ATP7B. Disease: Wilson disease.

PMID- 17230654
TI  - Gene symbol: ATP7B. Disease: Wilson disease.

PMID- 17230656
TI  - Gene symbol: CYP21A2. Disease: steroid 21-hydroxylase deficiency.

PMID- 17230657
TI  - Gene symbol: CYP21A2. Disease: adrenal hyperplasia, CYP21.

PMID- 17230658
TI  - Gene symbol: GCK. Disease: diabetes, MODY.

PMID- 17230660
TI  - Gene symbol: APC. Disease: adenomatous polyposis coli.

PMID- 17230661
TI  - Clinical research in anaesthesia; randomized controlled trials or observational
      studies?

PMID- 17230662
TI  - New year, new faces. Handful of CEOs tapped before 'Auld Lang Syne' sang.

PMID- 17230663
TI  - Rebuilding in New Orleans. Feds set aside dollar 300 million for LSU Medical
      Center.

PMID- 17230665
TI  - HSJ Awards. Communications. Winner: NHS Greater Glasgow and Clyde.

PMID- 17230664
TI  - Skin cancer and surgical margins for basal cell carcinoma.

PMID- 17230697
TI  - Address in Physiology.

PMID- 17230666
TI  - HSJ Awards. Excellence in cancer care. Winner: Sussex Cancer Network.

PMID- 17230698
TI  - Notes on Amylolytic Ferments.

PMID- 17230699
TI  - On the Nature of Rigor Mortis.

PMID- 17230700
TI  - Report on the Progress of Anatomy: From 1st January to 1st July, 1866.

PMID- 17230701
TI  - Observations on the Comparative Microscopic Anatomy of the Cornea of Vertebrates.

PMID- 17230702
TI  - Report on the Progress of Physiology: From 1st January to 1st July, 1866.

PMID- 17230703
TI  - On the Work performed in Pile Driving.

PMID- 17230704
TI  - On the Influence of Accommodation on the Idea of Distance.

PMID- 17230705
TI  - Analytical, Critical, and other Notices, Letters, &c.

PMID- 17230707
TI  - On Two Widely Contrasted Forms of the Human Cranium.

PMID- 17230706
TI  - On Human Muscular Variations and their Relation to Comparative Anatomy.

PMID- 17230709
TI  - On a Variation in the Origin of the Long Buccal Nerve as elucidating its
      Physiology.

PMID- 17230708
TI  - On a Remarkable Mode of Gestation in an Undescribed Species of Arius.

PMID- 17230710
TI  - On the Actions of Muscles passing over more than One Joint.

PMID- 17230711
TI  - On the Retina of Amphibia and Reptiles.

PMID- 17230712
TI  - Account of the Dissection of a Bushwoman.

PMID- 17230713
TI  - On the Hutchinsonian Theory of the Action of the Intercostal Muscles.

PMID- 17230715
TI  - On the Conditions of the Protoplasmic Movements in the Eggs of Osseous Fishes.

PMID- 17230714
TI  - Researches on Muscular Irritability and the Relations which exist between Muscle,
      Nerve and Blood.

PMID- 17230717
TI  - On some Points in the Anatomy of the Chimpanzee.

PMID- 17230716
TI  - On the Musculus Sternalis.

PMID- 17230718
TI  - On Cases of Vagina Duplex et Uterus Simplex and of Saccated Uterus.

PMID- 17230719
TI  - On the Recent Researches Concerning the Sugar of Muscle.

PMID- 17230720
TI  - On the Osteology of the Insectivora.

PMID- 17230721
TI  - On the Brain of Dasypus Sexcinctus.

PMID- 17230722
TI  - Notes on an Instance of Irregularity in the Muscles around the Shoulder Joint.

PMID- 17230723
TI  - The Physical and Physiological Action of Medicines.

PMID- 17230724
TI  - Note on the Origin of Hyaline or Diaphanous Corpuscles.

PMID- 17230726
TI  - Observations on British Zoophytes and Protozoa.

PMID- 17230725
TI  - On the Physiological Action of the Calabar Bean.

PMID- 17230727
TI  - On Poisoning by Carbonic Oxide Gas, and by Charcoal Fumes.

PMID- 17230728
TI  - On the Termination of the Nerves in the Conjunctiva.

PMID- 17230729
TI  - On a System of Perivascular Canals in the Nerve Centres, and on their
      Relationship to the Lymphatic System.

PMID- 17230731
TI  - Report on the Progress of Physiology: From 1st July, 1866, to 1st March, 1867.

PMID- 17230730
TI  - Report on the Progress of Anatomy.

PMID- 17230732
TI  - Analytical, Critical, and other Notices, Letters, &c.

PMID- 17230733
TI  - On the Colored Corpuscles of the Blood of Pyrenaematous and Apyrenaematous
      Vertebrates.

PMID- 17230734
TI  - On some New Methods of preserving thin Sections of Brain, or Spinal Cord, for
      Microscopical Examination.

PMID- 17230735
TI  - Note on a Three-toed Cow.

PMID- 17230737
TI  - Notes on the Osteology of the Insectivora.

PMID- 17230736
TI  - Preliminary Notice of some Observations with the Spectroscope on Animal
      substances.

PMID- 17230738
TI  - On Fovea Centralis in the Eye of the Fish.

PMID- 17230740
TI  - Report on the Progress of Anatomy.

PMID- 17230739
TI  - On a Case in which the Innominate Veins opened separately into the Right Auricle,
      and in which the Intestines were misplaced; with Remarks on the Development of
      the Parts.

PMID- 17230741
TI  - Report on the Progress of Physiology: From 1st March to 1st August, 1867.

PMID- 17230742
TI  - Notes on the Anatomy of the Retina of the Common Porpoise (Phocoena communis).

PMID- 17230743
TI  - Notices, Dutch and Scandinavian.

PMID- 17230744
TI  - Letters, &c.

PMID- 17230745
TI  - On the Arrangement of the Muscular Fibres of the Alligator.

PMID- 17230746
TI  - On the Skeleton of a Rickety Dwarf.

PMID- 17230747
TI  - On the Domestic Cats, Felis Domesticus and Mustela Foina, of Ancient and Modern
      Times.

PMID- 17230748
TI  - On a New Method of increasing the Pressure on the Artery in the use of the
      Sphygmograph.

PMID- 17230749
TI  - A Contribution to the Anatomy of the Pilot Whale (Globiocephalus Svineval,
      Lacepede).

PMID- 17230750
TI  - On the Nature of the Coronoid Portion of the Pronator Radii Teres.

PMID- 17230751
TI  - On the Morphology of the Arthropoda.

PMID- 17230752
TI  - Electrotonus.

PMID- 17230753
TI  - On an Abnormal Arrangement of the Peritoneum, with Remarks on the Development of
      the Mesocolon.

PMID- 17230754
TI  - Notes on the Myology of Viverra Civetta.

PMID- 17230755
TI  - Anatomical Description of a Case of Intra-peritoneal Hernia.

PMID- 17230756
TI  - Case of an Obliterated Right Internal Jugular Vein.

PMID- 17230757
TI  - On the Connection between Chemical Constitution and Physiological Action; with
      special reference to the Physiological Action of the Salts of the Ammonium Bases
      derived from Strychnia, Brucia, Thebaia, Codeia, Morphia, and Nicotia.

PMID- 17230758
TI  - On a Case of Congenital Malformation of the Fallopian Tubes, &c.

PMID- 17230760
TI  - An Account of an Enormous Tumour, presenting the Type of Structure of the Chorda
      Dorsalis.

PMID- 17230759
TI  - On a Supernumerary Oblique Muscle of the Eyeball.

PMID- 17230761
TI  - On the Form of the Cranium among the Patagonians and Fuegians, with some Remarks
      upon American Crania in general.

PMID- 17230762
TI  - The Relation of Digestion and Dyspepsia to Osmosis.

PMID- 17230763
TI  - On the Preparation of Fibrinogen and Fibrinoplastin.

PMID- 17230765
TI  - Notice of a Case of Malposition of the Right Kidney.

PMID- 17230764
TI  - On the Nourishment of the Foetus in Embiocotoid Fishes.

PMID- 17230766
TI  - On the Homologies of the Flexor Muscles of the Vertebrate Limb.

PMID- 17230767
TI  - On the Myology of Orycteropus Capensis and Phoca Communis.

PMID- 17230768
TI  - Note on the Anatomical Development of the Ruminant Stomach.

PMID- 17230769
TI  - On the Functions of the Buccal Branch of the Fifth Nerve.

PMID- 17230771
TI  - On the Epithelium of the Cornea of the Ox.

PMID- 17230770
TI  - Researches on the Nature and Action of Indian and African Arrow-poison.

PMID- 17230772
TI  - Notes on the Structure of a Monstrous Kitten.

PMID- 17230773
TI  - Report on the Progress of Anatomy.

PMID- 17230774
TI  - Report on the Progress of Physiology: From 1st August 1867, to 1st March 1868.

PMID- 17230775
TI  - Notices, Dutch and Scandinavian.

PMID- 17230776
TI  - Letters, &c.

PMID- 17230777
TI  - The Topographical Relations of the Arch of the Aorta and the Posterior
      Mediastinum to the Spinal Column.

PMID- 17230778
TI  - Notes on some Points in the Anatomy of the Perineum.

PMID- 17230779
TI  - Sesamoid Bone in the Tendon of the Supinator Brevis.

PMID- 17230780
TI  - Skull of an Otaria (Otaria Ulloae?) from the Chincha Islands.

PMID- 17230782
TI  - Further Observations on the Stomach in the Cetacea.

PMID- 17230781
TI  - Cranium of an apparently New Species of Arcto-Cephalus.

PMID- 17230783
TI  - Albuminous Substances of the Blood-Serum.

PMID- 17230784
TI  - Fibrin, a Constituent of the Stroma of the Red Blood-Corpuscles.

PMID- 17230786
TI  - The Ossification of the First and other Metacarpal and Metatarsal Bones.

PMID- 17230785
TI  - Effects of Rowing on the Circulation, as shown by the Sphygmograph.

PMID- 17230787
TI  - The Ciliary Muscle in Fish, Birds, and Quadrupeds.

PMID- 17230789
TI  - Report on the Progress of Anatomy.

PMID- 17230788
TI  - Reprint of the "Idea of a New Anatomy of the Brain," with Letters, &c.

PMID- 17230790
TI  - Report on the Progress of Physiology: From 1st March to 1st August, 1868.

PMID- 17230791
TI  - The Action of the Salts of Iron introduced into the Blood.

PMID- 17230792
TI  - Notices, Dutch and Scandinavian.

PMID- 17230794
TI  - The Thyro-hyoid Muscle.

PMID- 17230793
TI  - The Celtic Cranium.

PMID- 17230795
TI  - The Anal Fin Appendages of Embiotocoid Fishes.

PMID- 17230796
TI  - An Attempt to apply Chemical Principles in Explanation of the Action of Remedies
      and Poisons.

PMID- 17230797
TI  - The Homologies and Comparative Anatomy of the Atlas and Axis.

PMID- 17230798
TI  - Complete Obliteration of the Coeliae and Mesenteric Arteries: the Viscera
      receiving their Blood-Supply through the Extra-Peritoneal System of Vessels.

PMID- 17230799
TI  - Nomenclature of Mammalian Teeth, and the Dentition of the Mole and the Badger.

PMID- 17230800
TI  - The Valve of the Foramen Ovale.

PMID- 17230801
TI  - Dissection of Ectopia Vesicae.

PMID- 17230802
TI  - Changes in the Nervous System which follow the Amputation of Limbs.

PMID- 17230803
TI  - The Question whether the Eustachian Tube is Opened or Closed in Swallowing.

PMID- 17230804
TI  - Irregularities in the Arteries and Muscles of an Idiot.

PMID- 17230805
TI  - The Homologies and Notation of the Teeth of Mammalia.

PMID- 17230807
TI  - The Myology of the Limbs of Pteropus.

PMID- 17230806
TI  - The Anatomy of Stentor and its Mode of Division.

PMID- 17230808
TI  - The Disposition and Homologies of the Extensor and Flexor Muscles of the Leg and
      Forearm.

PMID- 17230809
TI  - The Arrangement of the Pronator Muscles in the Limbs of Vertebrate Animals.

PMID- 17230810
TI  - The Eustachian Tube, when and how is it opened?

PMID- 17230811
TI  - Note on the Mediastinum Thoracis.

PMID- 17230813
TI  - Tetanic Symptoms produced by Atropia in Cold-Blooded Animals; Paralytic and
      Convulsant Symptoms produced by Atropia in Frogs and in various Mammals.

PMID- 17230812
TI  - Additional Bone in the Carpus.

PMID- 17230814
TI  - The Action of the Horse.

PMID- 17230815
TI  - The Temperature in Diabetes.

PMID- 17230816
TI  - The Mechanism of Perching in Birds.

PMID- 17230817
TI  - Negro Crania from old Calabar, West Africa.

PMID- 17230818
TI  - The Cause of the Diastole of the Ventricles of the Heart.

PMID- 17230819
TI  - The Epithelium of the Frog's Throat.

PMID- 17230820
TI  - The Action of the Interrupted Current on the Ventricle of the Frog's Heart.

PMID- 17230821
TI  - Influence of the Vagus upon the Vascular System.

PMID- 17230822
TI  - The Fine Anatomy of the Skin of Lizards.

PMID- 17230823
TI  - On Ciliary Motion.

PMID- 17230824
TI  - Report on the Progress of Anatomy.

PMID- 17230825
TI  - Report on the Progress of Physiology: From 1st August, 1868 to 1st April, 1869.

PMID- 17230826
TI  - Communication made to Zoological Society.

PMID- 17230828
TI  - On the Spectroscopic Examination of Certain Animal Substances: Presented to the
      British Association at Exeter 1869.

PMID- 17230827
TI  - The Action of the Compounds of Chlorine Bromine and Iodine when introduced
      directly into the Blood.

PMID- 17230829
TI  - Note on some Peculiar Tumours found on the Gasterosteus Trachurus.

PMID- 17230830
TI  - Supernumerary Cervical Ribs.

PMID- 17230831
TI  - The so-called selective Absorption by the Lacteals and Lymphatics.

PMID- 17230832
TI  - Observations upon the Movements of the Chest.

PMID- 17230833
TI  - Note of a Case of Displacement of the Submaxillary Glands.

PMID- 17230834
TI  - Report on the Progress of Anatomy.

PMID- 17230835
TI  - Report on the Progress of Physiology: From 1st April to 1st August 1869.

PMID- 17230836
TI  - The Myology of the Limbs of the Unau, the Ai, the Two-toed Anteater, and the
      Pangolin.

PMID- 17230837
TI  - Notices of Recent Dutch and Scandinavian Contributions to Anatomical and
      Physiological Science.

PMID- 17230838
TI  - The late Dr Clark.

PMID- 17230839
TI  - Sketches of the Auditory Organs of certain Common Molluscs.

PMID- 17230840
TI  - The Action of the Horse.

PMID- 17230841
TI  - Note on the Arrangement of the Muscular Fibres of the Ventricles of the Heart.

PMID- 17230842
TI  - Chionis Alba.

PMID- 17230843
TI  - Note of a Supernumerary Lobe to the Right Lung.

PMID- 17230844
TI  - The Chemical Composition of the Nuclei of Blood Corpuscles.

PMID- 17230845
TI  - The Distal Communication of the Blood-Vessels with the Lymphatics; and on a
      Diaplasmatic System of Vessels.

PMID- 17230846
TI  - The Peritoneum of the Human Subject illustrated by that of the Wombat.

PMID- 17230847
TI  - Cause of the Supernumerary Lobe of the Right Lung.

PMID- 17230848
TI  - On the Action of the Inorganic Substances when introduced directly into the
      Blood.

PMID- 17230849
TI  - On the Organic Matter of Human Breath in Health and Disease.

PMID- 17230851
TI  - A Case of Asymmetry of the Two Halves of the Body.

PMID- 17230850
TI  - On the Cerebral Convolutions of a Deaf and Dumb Woman.

PMID- 17230852
TI  - Description of a Section Cutter for Microscopical Purposes.

PMID- 17230853
TI  - The Action of the Horse.

PMID- 17230854
TI  - Notes on Unusual Accessory Muscles.

PMID- 17230855
TI  - On the Correspondence between the Parts composing the Shoulder and the Pelvic
      Girdle of the Mammalia.

PMID- 17230856
TI  - Note of a Case of Abnormal Union of several of the Ribs.

PMID- 17230857
TI  - Description of a Foetal Brain.

PMID- 17230858
TI  - Notice of True Hermaphrodism in the Cod-Fish, and in the Herring.

PMID- 17230859
TI  - Note on the Preservation of Minute Animals in Acetic Acid.

PMID- 17230860
TI  - On the Species of Seal found in Scotland in Beds of Glacial Clay.

PMID- 17230861
TI  - Note on the Capture of the Grey Seal, Halichoerus Grypus, on the Coasts of Fife
      and Forfar.

PMID- 17230862
TI  - On the Sternum and Ossa Innominata of the Longniddry Whale.

PMID- 17230863
TI  - Remarks on Dr Davies' Paper on the Law which regulates the Relative Magnitude of
      the Areas of the Four Orifices of the Heart.

PMID- 17230864
TI  - Report on the Progress of Anatomy.

PMID- 17230866
TI  - Notices of Recent Dutch and Scandinavian Contributions to Anatomical and
      Physiological Science.

PMID- 17230865
TI  - Report on the Progress of Physiology: From 1st August, 1869, to 1st April, 1870.

PMID- 17230867
TI  - Some Points of Osteology of the Pichiciego.

PMID- 17230868
TI  - The Physical Relations of Consciousness and the Seat of Sensation, a Theory
      Proposed.

PMID- 17230869
TI  - Case in which in Man the Pericardium was unattached to the Diaphragm, with a
      Parallel Illustration from the Walrus.

PMID- 17230870
TI  - A Rudiment of the Panniculus Carnosus superficial to the Trapezius.

PMID- 17230871
TI  - Risso's Grampus: G. rissoanus (Desm.).

PMID- 17230872
TI  - The Specific Heat of Blood.

PMID- 17230873
TI  - Researches on the Constitution and Physiological Relations of Cystine
      (C(3)H(5)NO(2)S).

PMID- 17230875
TI  - The Relation which exists between the Iron contained in the Bile, and the
      Colouring Matter of Blood.

PMID- 17230874
TI  - Notes of some Experiments on the Rate of Flow of Blood and some other Liquids
      through Tubes of Narrow Diameter.

PMID- 17230876
TI  - Note on Dr Young's Paper.

PMID- 17230877
TI  - The Cranial Osteology of Polypterus.

PMID- 17230878
TI  - Cardiograph Tracings from the Human Chest-Wall.

PMID- 17230879
TI  - Report on the Progress of Anatomy.

PMID- 17230880
TI  - Report on the Progress of Physiology: From 1st April to 1st September, 1870.

PMID- 17230881
TI  - Notices of Recent Dutch and Scandinavian Contributions to Anatomical and
      Physiological Science.

PMID- 17230882
TI  - The Varieties of the Styloid Muscles.

PMID- 17230883
TI  - The Varieties of the Pronator Quadratus.

PMID- 17230885
TI  - The Loss of Solid Matter during the Germination and Early Growth of Plants.

PMID- 17230884
TI  - Contributions to the Cell-Migration Theory.

PMID- 17230886
TI  - The Homological Relations to one another of the Mesial and Lateral Fins of
      Osseous Fishes.

PMID- 17230887
TI  - A Comparison of the Shoulder Bones and Muscles with the Pelvic Bones and Muscles.

PMID- 17230888
TI  - The Action of the Horse.

PMID- 17230889
TI  - The Action of Nitrate of Amyl on the Circulation.

PMID- 17230890
TI  - Notes on some Variations of the Pectoralis Major, with its Associate Muscles.

PMID- 17230891
TI  - A Rudiment of the Dorsal Portion of the Panniculus Carnosus, superficial to the
      Trapezius.

PMID- 17230892
TI  - The Anatomy and Physiology of the so-called ;Salivary Glands' of the Common
      Cockroach-Periplaneta Orientalis.

PMID- 17230893
TI  - Observations of Physiological Chemistry.

PMID- 17230894
TI  - A Peculiar additional Digastric Muscle.

PMID- 17230895
TI  - Observations on the Physiological Action of the Hydrochlorate of Cotarnamic Acid.

PMID- 17230896
TI  - The Construction and use of a Simple Cardio-Sphygmograph.

PMID- 17230897
TI  - The Telson of the Macrurous Crustacea.

PMID- 17230898
TI  - Observations in Human Anatomy.

PMID- 17230900
TI  - Researches on the Action of Certain Drugs upon the Urine, and on the Influence of
      Diet and Mental Work upon this Excretion.

PMID- 17230899
TI  - Two Cases showing a Peculiar Arrangement in the Fibres of the External Pterygoid
      Muscle in Man.

PMID- 17230901
TI  - An Account of the Post-mortem Examination of a Case of Aneurism of the Abdominal
      Aorta Cured by Pressure.

PMID- 17230902
TI  - Ligamentous Action of the Trapezius Muscle Pathologically Illustrated.

PMID- 17230903
TI  - A Case of Epispadias, with Remarks.

PMID- 17230904
TI  - Some Improvements in the Mode of Making Sections of Tissues for Microscopic
      Observation.

PMID- 17230906
TI  - Notice of a Case of Peculiar Malformation of the Heart and Great Arteries.

PMID- 17230905
TI  - The Relative Excitability of Different Parts of the Trunk of a Spinal Nerve.

PMID- 17230907
TI  - Note on a Peculiar Origin of the Right Subclavian Artery.

PMID- 17230908
TI  - Remarks on a Young Aino Cranium.

PMID- 17230909
TI  - On the so-called Two-headed Ribs in Whales and in Man.

PMID- 17230911
TI  - Report on the Progress of Anatomy.

PMID- 17230910
TI  - On the Transverse Processes of the Seventh Cervical Vertebra in Balaenoptera
      Sibbaldii.

PMID- 17230912
TI  - Report on the Progress of Physiology: From 1st January to 1st April, 1871.

PMID- 17230913
TI  - The Muscles and Nerves of the Cryptobranchus Japonicus.

PMID- 17230914
TI  - Some Additional Variations in the Distribution of the Nerves of the Human Body.

PMID- 17230915
TI  - Some points in the Anatomy of a Great Fin-Whale.

PMID- 17230916
TI  - The Relation of the Temperature of the Air to that of the Body.

PMID- 17230917
TI  - The Malayan Tapir.

PMID- 17230918
TI  - The Sternum and Viscera of Pell's Owl.

PMID- 17230919
TI  - The Muscles and Nerves of a Chimpanzee (Troglodytes Niger) and a Cynocephalus
      Anubis.

PMID- 17230920
TI  - Partial Deficiency of the Tendon of the Long Flexor of the Thumb.

PMID- 17230921
TI  - Description of an Accessory Muscle in connection with the Popliteus.

PMID- 17230922
TI  - Uterine Contractions during Pregnancy.

PMID- 17230924
TI  - Report on the Progress of Physiology.

PMID- 17230923
TI  - Anomalies of Arrangement.

PMID- 17230925
TI  - A New Schema of the Circulation.

PMID- 17230926
TI  - The Composition of the Carpus of the Dog.

PMID- 17230927
TI  - Description of the Brain of an Idiot.

PMID- 17230928
TI  - Contribution to the Anatomy of the Shoulder of Birds.

PMID- 17230929
TI  - Contributions to the Anatomy of the Indian Elephant: Part I. The Thoracic
      Viscera.

PMID- 17230930
TI  - The Action of Inorganic Substances when introduced directly into the Blood.

PMID- 17230931
TI  - The Muscles of Lepidosiren Annectens, with the Cranial Nerves.

PMID- 17230933
TI  - The Muscles of Ceratodus.

PMID- 17230932
TI  - The Muscles of the Smooth Dog-Fish (Mustelus Levis).

PMID- 17230934
TI  - Notes on the Muscles of the Glass-Snake (Pseudopus Pallasii.

PMID- 17230935
TI  - The Disposition of Muscles in Vertebrate Animals.

PMID- 17230936
TI  - On the Sternum of the Sperm-Whale (Physeter Macrocephalus).

PMID- 17230937
TI  - Tissue Metabolism, or the Artificial Induction of Structural Changes in Living
      Organisms.

PMID- 17230938
TI  - The Homologue of a Mandibular Palp in Certain Insects.

PMID- 17230939
TI  - A Note on the Growth of the Masticatory Organs of Isopod Crustaceans.

PMID- 17230941
TI  - Some Remarks on the Anatomy of the Human Placenta.

PMID- 17230940
TI  - On Sphygmography.

PMID- 17230942
TI  - On the so-called Tailless Trout of Islay.

PMID- 17230943
TI  - Communication between the External Iliac and Portal Veins.

PMID- 17230944
TI  - Notes of Myological Peculiarities.

PMID- 17230945
TI  - Note upon Kryptophanic Acid.

PMID- 17230946
TI  - Note on the Presence of Trichina Spiralis in the Muscles of the Rat.

PMID- 17230947
TI  - Note on the Termination of the Thoracic Duct on the right side.

PMID- 17230948
TI  - Note of an Abnormality in the Human Dental Series.

PMID- 17230949
TI  - Report on the Progress of Anatomy.

PMID- 17230951
TI  - On the Cervical Vertebrae and their Articulations in Fin-Whales.

PMID- 17230950
TI  - Report on the Progress of Physiology.

PMID- 17230952
TI  - The Effect of Exercise on the Bodily Temperature.

PMID- 17230953
TI  - Observations on the Structure of the Human Placenta.

PMID- 17230954
TI  - Action of Digitalis on the Blood-Vessels.

PMID- 17230955
TI  - On the Kombe Arrow-Poison (Strophanthus Hispidus, D. C.) of Africa.

PMID- 17230957
TI  - Effect of Stimuli on the Secretion of the Parotid Gland.

PMID- 17230956
TI  - Peculiar Formation of the Leg and Foot.

PMID- 17230958
TI  - Valves in the Renal Veins.

PMID- 17230959
TI  - Experiments as to the Causes of the Presence of Bile Pigment in the Urine.

PMID- 17230960
TI  - Report on the Progress of Anatomy.

PMID- 17230962
TI  - Report on the Physiological Action of Medicinal and Poisonous Substances.

PMID- 17230961
TI  - Report on Physiology.

PMID- 17230963
TI  - Notice of Quadruple Mammae,-the Lower two Rudimentary,-in two Adult Brothers.

PMID- 17230964
TI  - Contributions to the Anatomy of the Indian Elephant (Elephas Indicus): Part II.
      Urinary and Generative Organs.

PMID- 17230965
TI  - Some Observations on the Dentition of the Narwhal (Monodon Monoceros).

PMID- 17230966
TI  - Tissue Metabolism, or the Artificial Induction of Structural changes in Living
      Organisms.

PMID- 17230967
TI  - Observations on the Distribution of some of the Nerves of the Head and Neck.

PMID- 17230968
TI  - On Sphygmography: Part II.

PMID- 17230969
TI  - On the Action of Inorganic Substances when introduced directly into the Blood.

PMID- 17230971
TI  - On the Law which regulates the Frequency of the Pulse.

PMID- 17230970
TI  - On the Physical Nature of the Coagulation of the Blood.

PMID- 17230972
TI  - A Contribution to the Visceral Anatomy of the Greenland Shark.

PMID- 17230974
TI  - Note on the Carpus of the Sloths.

PMID- 17230973
TI  - On the Source of Nerve Force. A Theory.

PMID- 17230975
TI  - On a Case of Hypertrophy of the Right Cerebral Hemisphere with Coexistent Atrophy
      of the Left Side of the Body.

PMID- 17230977
TI  - On the so-called Prickle or Claw at the end of the tail of the Lion and other
      Felines.

PMID- 17230976
TI  - On the Order Dinocerata.

PMID- 17230978
TI  - On an Edentulous Condition of the Skull of the Grey Seal.

PMID- 17230979
TI  - On the Physiological Action of Light: No. I.

PMID- 17230980
TI  - On the Physiological Action of Light: No. II.

PMID- 17230981
TI  - Cause of the Retardation of the Pulse which follows Artificial or Voluntary
      Closure of the Nostrils in the Rabbit: A Reply to certain Criticisms.

PMID- 17230982
TI  - Notes of Some Cases of Abnormal Arrangement of the Arteries of the Upper
      Extremity.

PMID- 17230983
TI  - On the Placentation of the Sloths.

PMID- 17230984
TI  - Notes of Some Irregularities in Muscles and Nerves.

PMID- 17230985
TI  - Case of Congenital Absence of the Quadriceps Extensor Cruris Muscle.

PMID- 17230986
TI  - Report on the Progress of Anatomy.

PMID- 17230987
TI  - Report on Physiology.

PMID- 17230988
TI  - THE VARIETIES IN THE MUSCLES OF MAN.

PMID- 17230989
TI  - The Causes of the Secondary Waves in the Pulse.

PMID- 17230990
TI  - The Subdivision of the Scaphoid Carpal Bone.

PMID- 17230991
TI  - Rudimentary Finger Muscles in a Whale.

PMID- 17230992
TI  - Tissue Metabolism.

PMID- 17230993
TI  - The Mechanism of opening and closing the Eustachian Tube.

PMID- 17230994
TI  - Note on a Bidental Skull of a Narwhal.

PMID- 17230995
TI  - Abnormal Ischio-Trochanteric Ligament.

PMID- 17230996
TI  - Depressions in the Parietal Bones of an Orang and in Man-Supernumerary Molars in
      Orang.

PMID- 17230998
TI  - Two cases of Persistent Communication between the Umbilical and Portal Veins.

PMID- 17230997
TI  - The Relations of the Cerebrum to the outer Surface of the Skull and Head.

PMID- 17230999
TI  - A Peculiar Digastric Muscle-a Variety of the Occipito-Hyoid.

PMID- 17231000
TI  - Experimental Researches in Cerebral Physiology and Pathology.

PMID- 17231001
TI  - Two instances of Irregular Ophthalmic and Middle Meningeal Arteries.

PMID- 17231002
TI  - Report on the Progress of Anatomy.

PMID- 17231003
TI  - Report on Physiology.

PMID- 17231004
TI  - Report on Pharmacology.

PMID- 17231005
TI  - The Amylolytic Ferment of the Pancreas.

PMID- 17231006
TI  - The Structure of Tactile Corpuscles.

PMID- 17231008
TI  - The Effects of a rise of Temperature on Reflex Actions in the Frog.

PMID- 17231007
TI  - The Structure of the Olfactory Mucous Membrane.

PMID- 17231009
TI  - The Law which regulates the frequency of the Pulse.

PMID- 17231010
TI  - Morphological Elements of the Skull.

PMID- 17231011
TI  - Double Nerve Stimulation.

PMID- 17231012
TI  - The Presence of an Insoluble sugar-forming Substance in Penicillium.

PMID- 17231013
TI  - Contributions to the Anatomy of the Indian Elephant: Part III. The Head.

PMID- 17231014
TI  - The apparent production of a new effect by the joint action of Drugs within the
      Animal Organism.

PMID- 17231015
TI  - An Account of the Madagascar Ordeal Poison.

PMID- 17231016
TI  - Some effects of Alcohol on Warm-blooded Animals.

PMID- 17231017
TI  - The Action of Inorganic Substances when introduced directly into the Blood.

PMID- 17231018
TI  - Double-bodied Monsters, and the Development of the Tongue.

PMID- 17231020
TI  - The Cartilages and Synovial Membranes of the Joints.

PMID- 17231019
TI  - Note on an Interesting Case of Malformation.

PMID- 17231021
TI  - The Acidity of Gastric Juice.

PMID- 17231022
TI  - Additional Observations on the Anatomy of the Greenland Shark (Laemargus
      Borealis).

PMID- 17231023
TI  - The Use of the Ligamentum Teres of the Hip-joint.

PMID- 17231024
TI  - Further Examples of Variations in the Arrangement of the Nerves of the Human
      Body.

PMID- 17231025
TI  - The Synthesis of Motion, Vital and Physical.

PMID- 17231026
TI  - Dissection of a Lamb with Fissure of the Sternum and Transposition of the Origin
      of the Right Subclavian Artery.

PMID- 17231027
TI  - The Sense of Rotation and the Anatomy and Physiology of the Semicircular Canals
      of the Internal Ear.

PMID- 17231028
TI  - Effect of Warmth in preventing Death from Chloral.

PMID- 17231029
TI  - The Septum Atriorum of the Frog and the Rabbit.

PMID- 17231030
TI  - Preliminary Note on an Epithelial Arrangement in front of the Retina and on the
      External Surface of the Capsule of the Lens.

PMID- 17231031
TI  - An Illustration of the Relations of the Convolutions of the Human Cerebrum to the
      Outer Surface of the Skull.

PMID- 17231032
TI  - The Placentation of the Sloths.

PMID- 17231033
TI  - Notes of some Muscular Irregularities.

PMID- 17231034
TI  - Notes of a Dissection of an Excised Elbow.

PMID- 17231036
TI  - Singular Malformation of Wrist and Hand.

PMID- 17231035
TI  - Note on an Unusually Large Renal Calculus.

PMID- 17231037
TI  - Report on the Progress of Anatomy.

PMID- 17231038
TI  - Report on Physiology.

PMID- 17231039
TI  - Contributions to the Anatomy of the Indian Elephant: Part IV. Muscles and Blood
      Vessels of the Face and Head.

PMID- 17231040
TI  - Notes of a Remarkable Case of Pharyngeal Diverticulum.

PMID- 17231041
TI  - The Position of the Heart's Impulse in Different Postures of the Body.

PMID- 17231042
TI  - A Description of the Cerebral and Spinal Nerves of Rana Esculenta.

PMID- 17231044
TI  - On the Minute Structure of the Retina and Vitreous Humour.

PMID- 17231043
TI  - Phoca Groenlandica as a British Species of Seal.

PMID- 17231045
TI  - On the Epitrochleo-Anconeus or Anconeus Sextus (Gruber).

PMID- 17231046
TI  - Variations of the Vertebrae and Ribs in Man.

PMID- 17231047
TI  - On the Urine Pigments.

PMID- 17231048
TI  - Abnormalities in the Arteries of the Upper Extremity.

PMID- 17231049
TI  - Dissection of an Abnormal Four-Toed Foetus without Head or Upper Limbs.

PMID- 17231050
TI  - Note on the Absence of the Quadratus Femoris Muscle and on a Spine possessing a
      Sixth Lumbar Vertebra, the First Rib being Rudimentary.

PMID- 17231051
TI  - Report on the Progress of Anatomy.

PMID- 17231052
TI  - Report on Physiology.

PMID- 17231053
TI  - The Development of the Powers of Thought in Vertebrate Animals in Connection with
      the Development of their Brain.

PMID- 17231054
TI  - Description of Three Cases of Malformation of the Spinal Column associated with
      Lateral Curvature.

PMID- 17231055
TI  - On the Freezing Process for Section-cutting: and on Various Methods of Staining
      and Mounting Sections.

PMID- 17231057
TI  - Lopsided Generations.

PMID- 17231056
TI  - Note on the Construction and Arrangement of Anatomical Museums.

PMID- 17231058
TI  - Observations on the Development and Structure of the Kidney.

PMID- 17231059
TI  - A Note on the Mechanical Work of Respiration.

PMID- 17231060
TI  - Case of Atrophy of Right Hemisphere of Cerebrum and Left Side of Cerebellum, with
      Atrophy of Left Side of Body.

PMID- 17231061
TI  - Observations on the Spiny Shark.

PMID- 17231062
TI  - On the Presence of Spiracles in the Porbeagle Shark (Lamna Cornubica).

PMID- 17231063
TI  - Notes on the Great Splanchnic Ganglion.

PMID- 17231064
TI  - Lateral Curvature of the Spine in Conjunction with Hypertrophy of the Sympathetic
      Nervous System in the Lumbar and Sacral Regions.

PMID- 17231066
TI  - The Characteristic sign of Cardiac Muscular Movement.

PMID- 17231065
TI  - Remarks on the Position of the Femur and on its so-called "True Neck.".

PMID- 17231067
TI  - Digestion-Oven with a Diffusion Apparatus.

PMID- 17231069
TI  - The Decomposition of Urea.

PMID- 17231068
TI  - On a Large Organised Cyst in the Sub-Dural Space.

PMID- 17231070
TI  - Notes on the Presence of two Precaval Veins in a Dog.

PMID- 17231072
TI  - Report on Physiology.

PMID- 17231071
TI  - Report on the Progress of Anatomy.

PMID- 17231073
TI  - On the Primary Vascular Dilatation in Acute Inflammation.

PMID- 17231075
TI  - On the Structure of Hyaline Cartilage.

PMID- 17231074
TI  - Note on certain peculiar Cells of the Cornea described by Dr Thin.

PMID- 17231076
TI  - On the Structure of the Diffused, the Polycotyledonary and the Zonary Forms of
      Placenta.

PMID- 17231078
TI  - On the Freezing Microtome: A Reply to Mr Lawson Tait.

PMID- 17231077
TI  - On the Origin and History of the Urinogenital Organs of Vertebrates.

PMID- 17231079
TI  - On a New Method of preparing the Skin for Histological Examination.

PMID- 17231080
TI  - The Action of Jaborandi on the Heart.

PMID- 17231082
TI  - On Articular Cartilage.

PMID- 17231081
TI  - Report on Physiology.

PMID- 17231083
TI  - The Brain and Cranial Nerves of Echinorhinus Spinosus, with Notes on the other
      Viscera.

PMID- 17231085
TI  - Experiments on the Biliary Secretion of the Dog.

PMID- 17231084
TI  - The Central Nervous System, the Cephalic Sacs, and other points in the Anatomy of
      the Lineidae.

PMID- 17231086
TI  - The Transformations of the Pulse-Wave in the different Arteries of the Body.

PMID- 17231087
TI  - Notes on the Broncho-OEsophageal and Pleuro-OEsophageal Muscles.

PMID- 17231088
TI  - The Summation of Electrical Stimuli applied to the Skin.

PMID- 17231089
TI  - The Development of Elasmobranch Fishes.

PMID- 17231090
TI  - The Nature of the Craniofacial Apparatus of Petromyzon.

PMID- 17231091
TI  - The Secondary Arches of the Foot.

PMID- 17231092
TI  - Note on the Placental Area in the Cat's Uterus after Delivery.

PMID- 17231093
TI  - Report on the Progress of Anatomy.

PMID- 17231094
TI  - A Contribution to the Anatomy of the Lens.

PMID- 17231095
TI  - On the Relative Powers of fresh and previously used Pepsine in the Digestion of
      Albumin.

PMID- 17231096
TI  - Contributions to the Anatomy of the Cutis of the Dog.

PMID- 17231097
TI  - Observations on Taste-Goblets in the Epiglottis of the Dog and Cat.

PMID- 17231098
TI  - On the Physiological Action of the Salts of Beryllium, Aluminium, Ythium, and
      Cerium.

PMID- 17231100
TI  - Note on the Abdominal Pores and Urogenital Sinus of the Lamprey.

PMID- 17231099
TI  - Physiological Action of Condurango.

PMID- 17231101
TI  - The Length of the Systole of the Heart, as estimated from Sphygmographic
      Tracings.

PMID- 17231103
TI  - On the Structure of the Snail's Heart.

PMID- 17231102
TI  - On the Mode of Oviposition of Amphioxus.

PMID- 17231104
TI  - Note on the Effects of Division of the Sympathetic Nerve of the Neck in Young
      Animals.

PMID- 17231105
TI  - On the Structure of the Non-Gravid Uterine Mucous Membrane in the Kangaroo.

PMID- 17231107
TI  - Additional Note on the Dentition of the Narwhal (Monodon monoceros).

PMID- 17231106
TI  - The Development of Elasmobranch Fishes.

PMID- 17231108
TI  - Remarks on the Anatomy of the Arms of the Crinoids.

PMID- 17231109
TI  - Some Effects of Upas Antiar on the Frog's Heart.

PMID- 17231110
TI  - Variations in the Arrangement of the Extensor Muscles of the Fore-Arm.

PMID- 17231111
TI  - A Simple Method of Demonstrating the Effect of Heat and Poisons upon the Heart of
      the Frog.

PMID- 17231112
TI  - Note on Pfluger's Law of Contraction.

PMID- 17231113
TI  - Note on the Action of the Internal Intercostal Muscles.

PMID- 17231114
TI  - The Oxidation of Urea.

PMID- 17231115
TI  - An Improved Freezing Microtome.

PMID- 17231116
TI  - Note on an Example of Meckel's Diverticulum.

PMID- 17231117
TI  - Report on Physiology.

PMID- 17231118
TI  - On the Comparison of the Fore and Hind Limbs in Vertebrates.

PMID- 17231119
TI  - The Development of Elasmobranch Fishes.

PMID- 17231120
TI  - On the Spinal Nerves of Amphioxus.

PMID- 17231121
TI  - On the Placentation of the Cape Ant-Eater (Orycteropus Capensis).

PMID- 17231122
TI  - Observations on the Galvanic Excitation of Nerve and Muscle, with special
      reference to the modification of the Excitability of Motor Nerves produced by
      Injury.

PMID- 17231123
TI  - The effects of the Constant Current on the Heart.

PMID- 17231124
TI  - A Contribution to the History of Development of the Guinea-Pig.

PMID- 17231125
TI  - Note on the Action of Diluted Alcohol on the Blood-Corpuscles.

PMID- 17231126
TI  - On Malformation of the Cardiac Septa: a Treatise on their Pathological Anatomy.

PMID- 17231127
TI  - Atrophy of Right Hemisphere of Cerebrum, Left Side of Cerebellum, and Left Half
      of Body.

PMID- 17231128
TI  - On the Development of the Mamma and of the Mammary Function.

PMID- 17231129
TI  - Supplementary Remarks on the Physiological Effects of Severe and Protracted
      Muscular Exercise, with especial Reference to its Influence upon the Excretion of
      Nitrogen.

PMID- 17231130
TI  - The Generative Organs of the Parasitic Isopoda.

PMID- 17231131
TI  - On the Digestive Ferment of Nepenthes.

PMID- 17231132
TI  - The Development of Elasmobranch Fishes.

PMID- 17231133
TI  - The Action of Pilocarpin on the Sub-Maxillary Gland of the Dog.

PMID- 17231134
TI  - On a New Staining-Fluid.

PMID- 17231135
TI  - Notes on a Case in which there was a Small Aperture in the Septum Ventriculorum
      near the Apex of the Heart.

PMID- 17231136
TI  - Report on Physiology.

PMID- 17231137
TI  - Some General Observations on the Placenta, with especial reference to the Theory
      of Evolution.

PMID- 17231139
TI  - Experiments on the Biliary Secretion of the Dog.

PMID- 17231138
TI  - On the Stomach of the Fresh-water Cray-Fish.

PMID- 17231140
TI  - Remarks on the Anatomy of the Arms of the Crinoids: Part II.

PMID- 17231141
TI  - On the Structure of the Retina.

PMID- 17231142
TI  - The Spinal Nervous System of the Porpoise and Dolphin.

PMID- 17231143
TI  - Notes of a Case of Double Aortic Arch.

PMID- 17231144
TI  - On the Action of Vanadium upon the Intrinsic Nervous Mechanism of the Frog's
      Heart.

PMID- 17231145
TI  - On the Poisonous Activity of Vanadium in Ortho-, Meta-, and Pyro- Vanadic Acids.

PMID- 17231147
TI  - On the Action of Pyro-Phosphoric Acid on the Circulation.

PMID- 17231146
TI  - On the Difference in the Poisonous Activity of Phosphorus in Ortho-, Meta- and
      Pyro-Phosphoric Acids.

PMID- 17231148
TI  - Observations on the Physiological Action of Chromium.

PMID- 17231149
TI  - Case of Univentricular or Tricoelian Heart.

PMID- 17231150
TI  - On the Changes in the Circulation which are induced when the Blood is expelled
      from the Limbs by Esmarch's Method.

PMID- 17231151
TI  - On the Effects of Sulphate of Atropia on the Nervous System of Frogs.

PMID- 17231152
TI  - A Contribution to the History of Development of the Guinea-Pig.

PMID- 17231154
TI  - Note on Case of Atrophy of Right Hemisphere of Cerebrum, Left Cerebellum, &c.

PMID- 17231153
TI  - On the Physiology of the Dehiscence of the Fruit of Momordica Elaterium.

PMID- 17231155
TI  - Note on the Lobules and the Connective Tissue of the Camel's Liver.

PMID- 17231156
TI  - A Contribution to the Minute Anatomy of the Human Retina.

PMID- 17231157
TI  - The Changes of the Blood-stream in Muscles through Stimulation of their Nerves.

PMID- 17231158
TI  - A Circulation Stage, a Live-development Slide, and an Improved Drawing Reflector.

PMID- 17231159
TI  - The Development of Elasmobranch Fishes.

PMID- 17231160
TI  - The Early Stages of Development of the Nerves in Birds.

PMID- 17231161
TI  - Further Observations and Experiments regarding the true Nature of Tetanus.

PMID- 17231162
TI  - The Extent to which Absorption can take place through the Skin of the Frog.

PMID- 17231163
TI  - Certain Molar Movements of the Human Body produced by the Circulation of the
      Blood.

PMID- 17231164
TI  - A New Freezing Microtome for the preparation of Sections of the Brain and Spinal
      Cord.

PMID- 17231165
TI  - Note on a Connecting Twig between the Anterior Divisions of the First and Second
      Dorsal Nerves.

PMID- 17231166
TI  - Report on Physiology.

PMID- 17231167
TI  - The Formation of Fat in the Animal Body.

PMID- 17231168
TI  - The Influence of Salicine on the Healthy Body with special reference to its
      Influence on the Temperature.

PMID- 17231169
TI  - The Cranial Osteology of Amia Calva.

PMID- 17231170
TI  - Experiments on the Biliary Secretion of the Dog.

PMID- 17231171
TI  - Description of a Sulu Skull, and Suggestions for conducting Craniological
      Researches.

PMID- 17231172
TI  - The Development of Elasmobranch Fishes.

PMID- 17231174
TI  - The Vasomotor Nerves of Striated Muscles.

PMID- 17231173
TI  - The Quantitative Relation of Light to Sensation.-A Contribution to the Physiology
      of the Retina.

PMID- 17231175
TI  - Note on the Effect of Heat on the Heart's Action in the Chick.

PMID- 17231176
TI  - Note on Mr Gordon's Paper ;On Certain Molar Movements, etc.'.

PMID- 17231177
TI  - The Therapeutics of Diphtheria: An Experimental Inquiry.

PMID- 17231178
TI  - Case of Supernumerary Upper Incisor Tooth.

PMID- 17231179
TI  - A Simple Form of Transmission Sphygmograph.

PMID- 17231180
TI  - The Placentation of Lemurs.

PMID- 17231181
TI  - Suggestions on some Points of Anatomical Nomenclature.

PMID- 17231182
TI  - Some Points in the Anatomy of Pentacrinus and Rhizocrinus.

PMID- 17231183
TI  - The Action of Chloride of Potassium on the Nervous System of Frogs.

PMID- 17231184
TI  - The Influence on the Afferent Nerves of the Frog's Leg from the Local Application
      of the Chlorides, Bromides, and Iodides of Potassium, Ammonium, and Sodium.

PMID- 17231185
TI  - The Effect of the Chlorides, Bromides, and Iodides of Potassium and Sodium on
      Frogs.

PMID- 17231186
TI  - The Mammillary and Accessory Processes as Persistent Epiphyses.

PMID- 17231187
TI  - The Source of Muscular Power, as Deduced from Observations upon the Human Subject
      under conditions of Rest and of Exercise.

PMID- 17231188
TI  - The Development of Elasmo-branch Fishes.

PMID- 17231189
TI  - Account of Rudimentary Finger Muscles found in the Greenland Right-Whale.

PMID- 17231190
TI  - The Fecundity and Placentation of the Shanghai River Deer.

PMID- 17231191
TI  - On Valvular Structures in the Umbilical Arteries.

PMID- 17231192
TI  - On Vascular Peribranchial Spaces in the Lamprey.

PMID- 17231193
TI  - Notes on a Case of Abnormal Arrangement of the Peritoneum.

PMID- 17231194
TI  - A Human Cerebrum Imperfectly Divided into two Hemispheres.

PMID- 17231195
TI  - A New Method of Preparing Large Sections of the Nervous Centres for Microscopic
      Investigation.

PMID- 17231197
TI  - On the Growth of the Jaws.

PMID- 17231196
TI  - Anatomy of the Indian Elephant.

PMID- 17231198
TI  - Notes on Hypertrophy of the Sympathetic Nervous System.

PMID- 17231199
TI  - Experiments on Tetanus.

PMID- 17231200
TI  - Localisation of Functions of the Brain: Being an Historical and Critical Analysis
      of the Question.

PMID- 17231201
TI  - A Pathological Function of Periosteum.

PMID- 17231202
TI  - A Peculiar Appearance in a Rabbit's Liver.

PMID- 17231203
TI  - A Rare Congenital Malformation of the Leg: With an Anatomical Description of the
      Parts by Johnson Symington, M.B., M.R.C.S.

PMID- 17231204
TI  - Anatomy of the Indian Elephant.

PMID- 17231205
TI  - Blood-Corpuscles of Annelides.

PMID- 17231206
TI  - The Nerves of the Fore-Limb of the Thylacine (Thylacinus Cynocephalus or
      Harrisii) and Cuscus (Phalangista Maculata).

PMID- 17231207
TI  - The Intrinsic Muscles of the Hand of the Thylacine (Thylacinus Cynocephalus),
      Cuscus (Phalangista Maculata), and Phascogale (Phascogale Calura).

PMID- 17231208
TI  - The Dissection of a Case of Dislocation of the Head of the Right Radius Forwards,
      with Elongation of the Bone.

PMID- 17231209
TI  - Do Bacteria or their Germs Exist in the Organs of Healthy Living Animals?

PMID- 17231210
TI  - Localisation of Functions of the Brain: Being an Historical and Critical Analysis
      of the Question.

PMID- 17231211
TI  - The Placentation of the Apes, with a Comparison of the Structure of their
      Placenta with that of the Human Female.

PMID- 17231212
TI  - Contributions to the Systematic Botany of Vegetable Parasites, with Experimental
      Researches on the Diseases Produced by them.

PMID- 17231214
TI  - Brain in Cyclopians.

PMID- 17231213
TI  - The Growth and Maintenance of the Articular Ends of Adult Bones.

PMID- 17231216
TI  - Attempt to obtain Mechanical Equivalent to Power of Growth in Aerial Leaves.

PMID- 17231215
TI  - Cutaneous Ligaments of the Phalanges.

PMID- 17231217
TI  - The Formation of the Placenta in the Guinea-Pig.

PMID- 17231218
TI  - The Vascular System of Branchiobdella, and the Blood-Corpuscles of the Earthworm.

PMID- 17231219
TI  - Some Rare Prints of Stranded Sperm Whales.

PMID- 17231220
TI  - The Foetal Membranes of the Rain-Deer (Rangifer tarandus).

PMID- 17231221
TI  - The Oviducts of the Greenland Shark (Loemargus borealis).

PMID- 17231222
TI  - Some Physical Experiments relating to the Functions of the Kidney.

PMID- 17231223
TI  - The Mode of Demonstrating Pfluger's Law of Contraction.

PMID- 17231224
TI  - Localisation of Functions of the Brain: Being an Historical and Critical Analysis
      of the Question.

PMID- 17231225
TI  - The Intrinsic Muscles of the Mammalian Foot.

PMID- 17231226
TI  - Case of Hemiplegia from an Injury involving Loss of Brain.

PMID- 17231228
TI  - Three Anatomical Notes and Two Anatomical Queries.

PMID- 17231227
TI  - Experiments on the Physiological Effects of the Inhalation of Gases-Phosphuretted
      Hydrogen.

PMID- 17231229
TI  - The Ovum and Placenta of the Dugong (Het Ei en de Placenta van Halicore Dugong).

PMID- 17231230
TI  - Abstract of Physiological Papers.

PMID- 17231231
TI  - The Anatomy of the Indian Elephant.

PMID- 17231232
TI  - A Theory of the Homology of the Suprarenals, based on Observations.

PMID- 17231233
TI  - The Anatomy of Genu Valgum.

PMID- 17231234
TI  - The Growth of Bone from the Articular Cartilages.

PMID- 17231235
TI  - A Tumour of the Ovary in the Common Pheasant.

PMID- 17231237
TI  - The Development of the Organ of Corti.

PMID- 17231236
TI  - The Placenta of the Hog-Deer (Cervus porcinus).

PMID- 17231238
TI  - Observations on the Structure of the Brain of the White Whale (Delphinapterus
      leucas).

PMID- 17231239
TI  - The Optic Nerve Fibres and Ganglion Cells of the Mammalian Retina.

PMID- 17231240
TI  - The Movements of the Iris.

PMID- 17231241
TI  - Three Cases of Axillary Mammary Tumour (with Observations).

PMID- 17231242
TI  - Abnormal Arrangement of the Branches of the Femoral Artery. Note on the Absence
      of the Profunda Femoris.

PMID- 17231243
TI  - Notes on the Tenacity of Tissue.

PMID- 17231244
TI  - Note on a Variation in the Course of the Popliteal Artery.

PMID- 17231245
TI  - Note on a Method for Measuring the Diameter of the Retinal Vessels.

PMID- 17231246
TI  - Remarkable Double Monstrosity of the Head.

PMID- 17231247
TI  - Further Observations on the Formation of the Placenta in the Guinea-Pig.

PMID- 17231248
TI  - The Physiological Type of the Giant-Cells of Tubercles and Granulations.

PMID- 17231249
TI  - The Cotyledonary and Diffused Placenta of the Mexican Deer (Cervus Mexicanus).

PMID- 17231250
TI  - Exostoses within the External Auditory Meatus.

PMID- 17231251
TI  - The Anatomy of the Quadriceps Extensor Cruris.

PMID- 17231252
TI  - Observations on the Influence of an Electro-Magnet on some of the Phenomena of a
      Nerve.

PMID- 17231253
TI  - The Action of Anaesthetics.

PMID- 17231255
TI  - Ueber die nach Nekrose an der Diaphyse der Langen Extremitatenknochen
      auftretenden Storungen in Langenwachstum derselben.

PMID- 17231254
TI  - Note on the Preservation of Encephala by the Zinc Chloride.

PMID- 17231256
TI  - Report on Physiological Chemistry.

PMID- 17231257
TI  - Report on Recent Physiological Papers.

PMID- 17231258
TI  - Report on Recent Memoirs of the Anatomy of the Brain.

PMID- 17231259
TI  - Obliteration of Vena Cava Inferior, with great Stenosis of Orifices of Hepatic
      Veins.

PMID- 17231260
TI  - The Male Generative Organs of the Koala (Phascolarctos cinereus).

PMID- 17231261
TI  - Some Bones of a Fossil Seal from the Post-Tertiary Clay at Dunbar.

PMID- 17231262
TI  - A New Variety of Ocular Spectrum.

PMID- 17231263
TI  - Some Points connected with the Physiological Action of Pilocarpine.

PMID- 17231264
TI  - The Circulatory System of Magelona.

PMID- 17231265
TI  - The Arrangement of the Azygos and Superior Intercostal Veins in the Thorax.

PMID- 17231266
TI  - Note on a Curious Habit of the Malapterurus Electricus.

PMID- 17231267
TI  - The Development of the Ova, and the Structure of the Ovary in Man and other
      Mammalia; with Special Reference to the Origin avd Development of the Follicular
      Epithelial Cells.

PMID- 17231268
TI  - Notes on the Dissection of a Negro.

PMID- 17231269
TI  - The Effects of Chloroform, Ethidene, and Ether on the Blood-Pressure: Being the
      Third Provisional Report of the Committee on Anaesthetics to the Scientific
      Grants Committee of the British Medical Association.

PMID- 17231270
TI  - Unusual Abnormality of the Arteries at the Base of the Brain.

PMID- 17231271
TI  - Note on the Distribution of the Anterior Tibial Nerve on the Dorsum of the Foot.

PMID- 17231272
TI  - A Loop-Like Bifurcation of the External Carotid Artery.

PMID- 17231273
TI  - The Organ of Bojanus in Anodon.

PMID- 17231274
TI  - Morphology of the Mammalian Ossicula Auditus.

PMID- 17231275
TI  - Report on Recent Physiological Memoirs.

PMID- 17231277
TI  - Supernumerary Nipples and Mammae: With an Account of Sixty-five Instances
      observed.

PMID- 17231276
TI  - Abstracts of Pathological Papers: Evidence for the Unity of Phthisis.

PMID- 17231278
TI  - The Origin and Composition of the Bodies found in Compound Ganglia.

PMID- 17231280
TI  - The Form and Structure of the Teeth of Mesoplodon Layardii and Mesoplodon
      Sowerbyii.

PMID- 17231279
TI  - The Physiology of the Turkish Bath: Being an Experimental Inquiry into the
      Effects of Hot Dry Air upon Man.

PMID- 17231281
TI  - The Element of Symbolic Correlation in Expression.

PMID- 17231282
TI  - An Intra-thoracic Lymphoid Tumour.

PMID- 17231283
TI  - Inequality in Length of the Lower Limbs.

PMID- 17231284
TI  - A Large Sub-arachnoid Cyst involving the greater part of the Parietal Lobe of the
      Brain.

PMID- 17231285
TI  - The Process of Healing.

PMID- 17231286
TI  - The Dentition of Hypsiprymnus (Bettongia) Penicillatus, Gray.

PMID- 17231287
TI  - New Theory of Contraction of Striated Muscle, and Demonstration of the
      Composition of the Broad Dark Bands.

PMID- 17231289
TI  - Note to Professor Scott's Paper.

PMID- 17231288
TI  - Note of a Case of Articulation between two Ribs.

PMID- 17231290
TI  - Additional Note on the Organ of Bojanus.

PMID- 17231291
TI  - A Two-Headed Sartorius.

PMID- 17231292
TI  - Note on Ethidene.

PMID- 17231293
TI  - Presternal Fissure uncovering the Base of the Heart.

PMID- 17231294
TI  - Case of Congenital and Progressive Hypertrophy of the Right Upper Extremity.

PMID- 17231295
TI  - The Pori Abdominales in Some Sharks.

PMID- 17231296
TI  - A Description of a Cleft Sternum.

PMID- 17231297
TI  - The Physiological Action of Ozonised Air.

PMID- 17231298
TI  - The Scapular Index as a Race Character in Man.

PMID- 17231299
TI  - The Mode of Propagation of Nervous Impulses.

PMID- 17231300
TI  - Note on Logwood Staining Solution.

PMID- 17231301
TI  - Case of Development of Hair on the Eyeball of a Dog.

PMID- 17231302
TI  - Note on Giacomini's Method of Preserving the Brain.

PMID- 17231303
TI  - The Morphology of the Olfactory Organs.

PMID- 17231304
TI  - The Placenta in the Sloth.

PMID- 17231306
TI  - Note by Professor Cleland on Dr Allen's Paper.

PMID- 17231305
TI  - The Varieties of the Atlas in the Human Subject, and the Homologies of its
      Transverse Processes.

PMID- 17231307
TI  - The Infection of the Connective Tissue in Scirrhous Cancers of the Breast.

PMID- 17231308
TI  - The Homology of the Sexual Organs Illustrated by Comparative Anatomy and
      Pathology.

PMID- 17231309
TI  - Pori Abdominales of Vertebrata.

PMID- 17231310
TI  - Intrinsic Muscles of the Marsupial Hand.

PMID- 17231311
TI  - Myology of Viverra Civetta.

PMID- 17231312
TI  - Anatomy of the Knee Joint.

PMID- 17231313
TI  - Development of Fibrous Tissue from the Hepatic Parenchyma in Cirrhosis of the
      Liver.

PMID- 17231314
TI  - Contributions to the Pathology of the Internal Ear.

PMID- 17231315
TI  - A New Bone in Human Anatomy: Together with an Investigation into the
      Morphological Significance of the so-called Internal Lateral Ligament of the
      Human Lower Jaw.

PMID- 17231316
TI  - The Disease called Sturdy in Sheep, in its Relation to Cerebral Localisation.

PMID- 17231317
TI  - Two Cases of Lesion of the Temporo-Sphenoidal Lobe of the Brain: With
      Pathological Examination.

PMID- 17231318
TI  - Two Cases of Striated Myo-Sarcoma of the Kidney.

PMID- 17231319
TI  - The Sequence and Duration of the Cardiac Movements.

PMID- 17231320
TI  - The Foetal Membranes of the Eland (Oreas canna).

PMID- 17231321
TI  - Notes on the Dissection of a Second Negro.

PMID- 17231322
TI  - A New Abnormality in connection with the Vertebral Artery.

PMID- 17231324
TI  - List of Grants in Aid of Scientific Investigation made by the British Medical
      Association.

PMID- 17231323
TI  - Case of Development of Wool on the Cornea of a Sheep.

PMID- 17231325
TI  - The Structure of the Comb-Like Branchial Appendages and of the Teeth of the
      Basking Shark (Selache maxima).

PMID- 17231326
TI  - Note on the Ganglion-Cells of the Elephant's Retina.

PMID- 17231327
TI  - Note on the Structure of the Style in the Tongue of the Dog.

PMID- 17231328
TI  - Note on the Anatomy of the Indian Elephant.

PMID- 17231330
TI  - On a Peculiar Form of Liver Tumour.

PMID- 17231329
TI  - Illustrations of the Pathology of Sarcoma, from Cases of Subcutaneous Cystic
      Tumours.

PMID- 17231331
TI  - Case of Cerebellar Tumour (Psammo-Sarcoma).

PMID- 17231332
TI  - Post-Mortem in a Case of Extreme Obesity.

PMID- 17231333
TI  - On the Head of the Lobster.

PMID- 17231334
TI  - New Abnormalities of the Arteries of the Upper Extremity.

PMID- 17231335
TI  - Abnormal Arrangement of the Thyroid Arteries.

PMID- 17231336
TI  - A Variety of the Mylopharyngeus and other Unusual Muscular Abnormalities.

PMID- 17231337
TI  - The Pathology of a Case of Fatal Ear Disease.

PMID- 17231338
TI  - Notes on the Dissection of a Case of Congenital Dislocation of the Head of the
      Femur.

PMID- 17231340
TI  - Anatomical Notices.

PMID- 17231339
TI  - Abnormal Cystic Artery.

PMID- 17231341
TI  - Account of a New Bone in Human Anatomy.

PMID- 17231342
TI  - The Rete Mirabile of the Narwhal.

PMID- 17231343
TI  - Observations on the Coronary Veins of the Stomach.

PMID- 17231345
TI  - A Communication between the Air-Bladder and the Cloaca in the Herring.

PMID- 17231344
TI  - Note on Mr Walsham's Observations on the Coronary Veins of the Stomach.

PMID- 17231346
TI  - The Curvatores Coccygis Muscles of Man.

PMID- 17231347
TI  - Valvular Haematoma.

PMID- 17231348
TI  - A Contribution to the Pathology of Macroglossia and Hygroma.

PMID- 17231349
TI  - The Changes in the Spinal Cord after Amputation of Limbs.

PMID- 17231350
TI  - The Morbid Anatomy of Certain Forms of Post-Scarlatinal Nephritis in Relation to
      their Bearing on the Histogeny of Granular Kidney.

PMID- 17231352
TI  - The Presence of an Astragalo-Scaphoid Bone in Man.

PMID- 17231351
TI  - The Antagonism of Opium and Belladonna, Illustrated by a Case of Attempted
      Suicide.

PMID- 17231353
TI  - The Mode of Healing in Wounds under Antiseptic Dressings.

PMID- 17231354
TI  - The Respiratory Movements of Fishes: No. 1.

PMID- 17231355
TI  - Some Points in the Anatomy of the Porpoise (Phocoena communis).

PMID- 17231356
TI  - Two Masks and a Skull from Islands near New Guinea-a Contribution to
      Anthropology.

PMID- 17231357
TI  - The Effect of certain Anaesthetics on the Pulmonary Circulation.

PMID- 17231358
TI  - A New Method of Preserving the Colours of Tissues.

PMID- 17231360
TI  - Anatomical and Physiological Notices.

PMID- 17231359
TI  - Variations in Myology.

PMID- 17231361
TI  - An Ether Percolator, for use in Physiological or Pathological Laboratories.

PMID- 17231362
TI  - The Comparative Value of Chloroform and Ethidene Dichloride as Anaesthetic
      Agents.

PMID- 17231364
TI  - The Lymphatics of Cartilage or of the Perichondrium.

PMID- 17231363
TI  - Observations on the Temperature of the Healthy Human Body in Various Climates.

PMID- 17231365
TI  - A Palatine Branch from the Middle Meningeal Artery.

PMID- 17231366
TI  - Muscular Anomalies.

PMID- 17231367
TI  - Tertiary Occipital Condyle.

PMID- 17231368
TI  - Some Points in the Histology of Cirrhosis of the Liver.

PMID- 17231369
TI  - A Contribution to the Pathological Anatomy of Lead-Paralysis.

PMID- 17231370
TI  - Vascular Lesions in Hydrophobia and in other Diseases characterised by Cerebral
      Excitement.

PMID- 17231371
TI  - An Infective Form of Tuberculosis in Man identical with Bovine Tuberculosis.

PMID- 17231372
TI  - An Infective Form of Tuberculosis in Man Identical with Bovine Tuberculosis.

PMID- 17231374
TI  - Dissection of the Genito-Urinary Organs in a case of Fissure of the Abdominal
      Walls.

PMID- 17231373
TI  - Case of Medullary Neuroma of the Brain.

PMID- 17231375
TI  - Description of a Polygraph.

PMID- 17231376
TI  - Remarks on the Mechanism of the Secretion of Sweat.

PMID- 17231377
TI  - Anomalous Growth Bearing Pilose Skin in the Pharynx of a Young Woman.

PMID- 17231378
TI  - The Histology of Granular Kidney.

PMID- 17231380
TI  - Some Observations on the Colouring Matter of Jelly Fishes.

PMID- 17231379
TI  - Notes on Two Cases of Cerebellar Disease.

PMID- 17231381
TI  - The Nerves of the Hind-Limb of the Thylacine (Thylacinus Harrisii or
      Cynocephalus) and Cuscus (Phalangista maculata).

PMID- 17231383
TI  - Anatomical Notices.

PMID- 17231382
TI  - Pulse Dicrotism.

PMID- 17231384
TI  - The Bones, Articulations, and Muscles of the Rudimentary Hind-Limb of the
      Greenland Right-Whale (Balaena mysticetus).

PMID- 17231385
TI  - The Bones, Articulations, and Muscles of the Rudimentary Hind-Limb of the
      Greenland Right-Whale (Balaena mysticetus).

PMID- 17231386
TI  - The Stridulating Apparatus of Callomystax Gagata.

PMID- 17231387
TI  - The Sternum as an Index of Sex and Age.

PMID- 17231389
TI  - The Membrana Propria of the Mammary Gland.

PMID- 17231388
TI  - The Mechanism of Costal Respiration.

PMID- 17231390
TI  - Double and Treble Staining of Microscopic Specimens.

PMID- 17231392
TI  - Notes on a Dissection of a Case of Epispadias.

PMID- 17231391
TI  - The Comparative Anatomy of the Lymphatics of the Mammalian Urinary Bladder.

PMID- 17231393
TI  - The Morphology of the Muscles of the Tongue and Pharynx.

PMID- 17231394
TI  - The so-called Movements of Pronation and Supination in the Hind-Limb of certain
      Marsupials.

PMID- 17231395
TI  - A Contribution to the Pathological Anatomy of Pneumonokoniosis (Chalicosis
      pulmonum).

PMID- 17231396
TI  - The Histology of some of the Rarer Forms of Malignant Bone Tumours.

PMID- 17231397
TI  - The Morbid Histology of the Liver in Acute Yellow Atrophy.

PMID- 17231399
TI  - Anatomical Notices.

PMID- 17231398
TI  - The Relationship between the Muscle and its Contraction.

PMID- 17231400
TI  - Anatomy of the Koala (Phascolarctos cinereus).

PMID- 17231401
TI  - The Lymphatics of the Pancreas.

PMID- 17231402
TI  - Case of Primary Cancer of the Femur.

PMID- 17231403
TI  - Case of Chronic Lobar Pneumonia.

PMID- 17231405
TI  - The Form and Proportions of a Foetal Indian Elephant.

PMID- 17231404
TI  - A Contribution to the Pathological Anatomy of Primary Lateral Sclerosis
      (Sclerosis of the Pyramidal Tracts).

PMID- 17231407
TI  - The Brain and Nervous System: A Summary and a Review.

PMID- 17231406
TI  - The Femoral Artery in Apes.

PMID- 17231408
TI  - The Ovary in Incipient Cystic Disease.

PMID- 17231409
TI  - The Relation of Nerve-Supply to Muscle-Homology.

PMID- 17231411
TI  - Pelvimetry.

PMID- 17231410
TI  - The Action of Duboisia on the Circulation.

PMID- 17231412
TI  - The Cranial Characters of the Admiralty Islanders.

PMID- 17231413
TI  - Report on Physiology: Selected Abstracts.

PMID- 17231414
TI  - Anatomical Notices.

PMID- 17231415
TI  - On the Cerebral Sinuses and their Variations.

PMID- 17231417
TI  - On the Reproduction of the "Feeler" of the Lobster's Antenna.

PMID- 17231416
TI  - Primary Growth from Bone, resembling in some of its Features Scirrhus Carcinoma
      of the Breast.

PMID- 17231418
TI  - On the Comparative Anatomy of the Lymphatics of the Uterus.

PMID- 17231419
TI  - A Case of Transposition of the Aorta and Pulmonary Artery in a Child of Seven
      Months.

PMID- 17231420
TI  - On some Points in the Histology of the Newt.

PMID- 17231421
TI  - On the Nerves of the Lungs of the Newt.

PMID- 17231422
TI  - Observations on the Histology of Fracture Repair in Man.

PMID- 17231423
TI  - Colloid Degeneration of the Non-Cystic Ovary, with associated Vascular Changes.

PMID- 17231424
TI  - On the Phalanx missing from certain Digits in the Manus of Chiroptera.

PMID- 17231425
TI  - The Histology of Molluscum Contagiosum.

PMID- 17231427
TI  - The Muscular Anatomy of the Koala (Phascolarctos cinereus): With Additional
      Notes.

PMID- 17231426
TI  - Case of Obliteration of the Portal Vein (Pylephlebitis Adhesiva).

PMID- 17231428
TI  - The Action of Saline Cathartics.

PMID- 17231430
TI  - Anatomical Notices.

PMID- 17231429
TI  - Researches on the Gases of the Bile.

PMID- 17231431
TI  - The Segmental Value of the Cranial Nerves.

PMID- 17231432
TI  - The Anatomy of Microgale Longicauda, with Remarks on the Homologies of the Long
      Flexors of the Toes in Mammalia.

PMID- 17231433
TI  - The Curled Hair and Curved Hair Follicle of the Negro.

PMID- 17231434
TI  - Some of the Pathological Conditions of the Medulla Oblongata, &c., in a Case of
      Locomotor Ataxia (Tabes Dorsalis).

PMID- 17231435
TI  - The Action of Saline Cathartics.

PMID- 17231436
TI  - Abnormal Origin and Distribution of the Upper Seven Right Intercostal Arteries,
      with Remarks.

PMID- 17231437
TI  - On the Digestion of Blood by the Common Leech, and on the Formation of
      Haemoglobin Crystals.

PMID- 17231438
TI  - A Specimen of Sowerby's Whale (Mesoplodon bidens), Captured in Shetland.

PMID- 17231439
TI  - A Specimen of Rudolphi's Whale (Baloenoptera borealis or laticeps), Captured in
      the Firth of Forth.

PMID- 17231440
TI  - Note on the Anatomy of the Thyro-Arytenoid Muscle in the Human Larynx.

PMID- 17231442
TI  - Observations in Comparative Myology.

PMID- 17231441
TI  - Physiological Notices.

PMID- 17231443
TI  - Fat Embolism.

PMID- 17231445
TI  - The Action of Saline Cathartics.

PMID- 17231444
TI  - Micrococcus Poisoning.

PMID- 17231446
TI  - A Variety of Pulmonary Lobation and its Relations to the Thoracic Parietes, as
      illustrated by Comparative Anatomy and Abnormalities in the Human Subject.

PMID- 17231447
TI  - Critical Remarks on Polydactyly as Atavism.

PMID- 17231448
TI  - The Lymphatics of the Walls of the Larger Blood-Vessels and Lymphatics.

PMID- 17231449
TI  - A "Kerato-thyro-hyoid" Muscle as a Variation in Human Anatomy.

PMID- 17231450
TI  - Micrococcus Poisoning.

PMID- 17231451
TI  - Omphalo-Mesenteric Remains in Mammals.

PMID- 17231452
TI  - The Action of Saline Cathartics.

PMID- 17231453
TI  - A Hitherto Undescribed Fracture of the Astragalus.

PMID- 17231455
TI  - Note on the Rectus Abdominis et Sternalis Muscle.

PMID- 17231454
TI  - A Secondary Astragalus in the Human Foot.

PMID- 17231456
TI  - Ectopia Vesicae and other Imperfections of Development in a New-Born Infant.

PMID- 17231457
TI  - Nickel and Cobalt: Their Physiological Action on the Animal Organism: Part I.
      Toxicology.

PMID- 17231458
TI  - A Method for the Estimation of Urea in the Blood: Part I.

PMID- 17231459
TI  - On the Homologies of the Long Flexor Muscles of the Feet of Mammalia, with
      remarks on the Value of their Leading Modifications in Classification.

PMID- 17231460
TI  - Obliterative Endarteritis, and the Inflammatory Changes in the Coats of the Small
      Vessels.

PMID- 17231461
TI  - The Presence of a Tympanum in the Genus Raia.

PMID- 17231462
TI  - The Ligamentum Teres.

PMID- 17231463
TI  - Fibrinous Coagula in the Left Ventricle.

PMID- 17231464
TI  - A Simple Method of Demonstrating the Nerves of the Epiglottis.

PMID- 17231465
TI  - The Trachealis Muscle of Man and Animals.

PMID- 17231466
TI  - The Sulphocyanides of Ammonium and Potassium as Histological Reagents.

PMID- 17231467
TI  - A New Theory as to the Functions of the Semicircular Canals.

PMID- 17231468
TI  - Some Points in the Myology of the Common Pigeon.

PMID- 17231469
TI  - The Action of Saline Cathartics.

PMID- 17231470
TI  - Some Variations in the Bones of the Human Carpus.

PMID- 17231471
TI  - Multiple Renal Arteries.

PMID- 17231472
TI  - Division of the Scaphoid Bone of the Carpus, with Notes on other Varieties of the
      Carpal Bones.

PMID- 17231473
TI  - A First Dorsal Vertebra, with a Foramen at the Root of the Transverse Process.

PMID- 17231474
TI  - Contribution to the Study of Spina Bifida, Encephalocele, and Anencephalus.

PMID- 17231475
TI  - The Minute Structure of the Palatine Nerves of the Frog, and the Termination of
      Nerves in Blood-Vessels and Glands.

PMID- 17231476
TI  - The Lymphatics of Periosteum.

PMID- 17231477
TI  - The Brachial Plexus of the Macaque Monkey and its Analogy with that of Man.

PMID- 17231478
TI  - A Case of Primary Sarcoma of the Pleura.

PMID- 17231479
TI  - Infiltrating Carcinoma of Breast.

PMID- 17231480
TI  - Observations on the Diameters of Human Vertebrae in Different Regions.

PMID- 17231481
TI  - Note on a Simple Form of Lippmann's Capillary Electrometer useful to
      Physiologists.

PMID- 17231482
TI  - On So-Called Sponge-Grafting.

PMID- 17231484
TI  - Origin of the Internal Circumflex from the Deep Epigastric Artery.

PMID- 17231483
TI  - The Valvular Action of The Larynx.

PMID- 17231485
TI  - Cervical Ribs, and the So-Called Bicipital Ribs in Man, in Relation to
      Corresponding Structures in the Cetacea.

PMID- 17231487
TI  - Right-Sided Sigmoid Flexure and Rectum.

PMID- 17231486
TI  - New Form of Ether Microtome.

PMID- 17231488
TI  - Note to Mr. Haswell's Paper on Myology of Pigeon.

PMID- 17231490
TI  - Some Remarks on the Anatomy and Physiology of the Urinary Bladder, and of the
      Sphinoters of the Rectum.

PMID- 17231489
TI  - The Action of Saline Cathartics.

PMID- 17231491
TI  - Ten Cases of Congenital Contraction of the Stomach: With Remarks.

PMID- 17231492
TI  - A New Rule of Epiphyses of Long Bones.

PMID- 17231493
TI  - Notes on Three Cases of Cerebellar Disease.

PMID- 17231494
TI  - A Contribution to the Anatomy of the Indian Elephant.

PMID- 17231495
TI  - Note on a Specimen of Absence of the Parts Developed from the First Visceral Arch
      on One Side in a Lamb (Semi-Agnathia or Synotia).

PMID- 17231496
TI  - The Ossification of the Temporal Bone.

PMID- 17231497
TI  - Case of Primary Epithelioma of the Lung, with Secondary Deposits in the Kidney,
      Vertebrae, and Ribs.

PMID- 17231498
TI  - Researches into the Histology of the Central Grey Substance of the Spinal Cord
      and Medulla Oblongata.

PMID- 17231499
TI  - On the Membrana Tympani.

PMID- 17231500
TI  - An Account of an Obturator Hernia.

PMID- 17231501
TI  - Fibrous Body Attached to the Hydatid of Morgagni.

PMID- 17231502
TI  - Short Notes on the Myology of the American Black Bear (Ursus americanus).

PMID- 17231503
TI  - Note respecting the Course of the Flexor Longus Digitorum Pedis.

PMID- 17231504
TI  - Total Absence of the Left Lobe of the Thyroid Body.

PMID- 17231505
TI  - The Os Centrale in the Human Carpus.

PMID- 17231506
TI  - On the Action of Infused Beverages on Peptic Digestion.

PMID- 17231507
TI  - On a Method of Promoting Maceration for Anatomical Museums by Artificial
      Temperature.

PMID- 17231508
TI  - On the Wax-like Disease of the Heart.

PMID- 17231509
TI  - On the Relations of the Dorsal Artery of the Foot to the Cuneiform Bones.

PMID- 17231510
TI  - Researches into the Histology of the Central Grey Substance of the Spinal Cord
      and Medulla Oblongata: Part II.

PMID- 17231511
TI  - On some Points in the Anatomy of the Chimpanzee (Anthropopithecus Troglodytes).

PMID- 17231512
TI  - Observations upon the Osteology of Podasocys Montanus.

PMID- 17231513
TI  - The Development of the Suspensory Ligament of the Fetlock in the Foetal Horse,
      Ox, Roe-Deer, and Sambre-Deer.

PMID- 17231514
TI  - The Urea Elimination under the Use of Potassium Fluoride in Health.

PMID- 17231516
TI  - The Transverse Measurements of Human Ribs.

PMID- 17231515
TI  - Primary Sarcoma of the Kidney.

PMID- 17231517
TI  - A Method of Determining the Position of the Fissure of Rolando and some other
      Cerebral Fissures in the Living Subject.

PMID- 17231518
TI  - New Forms of Nerve Terminations in Mammalian Skin.

PMID- 17231519
TI  - The Fold of the Nates.

PMID- 17231520
TI  - Researches into the Histology of the Central Grey Substance of the Spinal Cord
      and Medulla Oblongata: Part III.

PMID- 17231521
TI  - The Musculus Sternalis.

PMID- 17231522
TI  - Movements of the Shoulder Girdle involved in those of the Arm on the Trunk.

PMID- 17231523
TI  - The Relation of the Orbito-Sphenoid to the Region Pterion in the Side Wall of the
      Skull.

PMID- 17231524
TI  - Anatomical Notices.

PMID- 17231525
TI  - Certain Abnormal Conditions of the Reproductive Organs in the Frog.

PMID- 17231526
TI  - Some Remarks on Nervous Exhaustion and on Vaso-Motor Action.

PMID- 17231527
TI  - The Development of the Great Omentum and Transverse Mesocolon.

PMID- 17231528
TI  - Notes on Two Instances of Abnormality in the Course and Distribution of the
      Radial Artery.

PMID- 17231529
TI  - The Cause of the First Sound of the Heart, and the Mode of Action of the Cardiac
      Muscle.

PMID- 17231530
TI  - Notes on Raising the Arm.

PMID- 17231531
TI  - Osteology of Ceryle alcyon.

PMID- 17231532
TI  - Notes on Abnormalities, with Special Reference to the Vertebral Arteries.

PMID- 17231534
TI  - Notes on the Viscera of the Porpoise and White-Beaked Dolphin.

PMID- 17231533
TI  - On Multiple Lymphatic Naevi of the Skin, and their Relation to some Kindred
      Diseases of the Lymphatics.

PMID- 17231535
TI  - Costal and Sternal Asymmetry.

PMID- 17231536
TI  - Anatomical Notices.

PMID- 17231537
TI  - The Nature of Certain Ligaments.

PMID- 17231538
TI  - Terminal Forms of Life.

PMID- 17231540
TI  - On the Presence of Peyer's Patches (Glandulae Agminatae) in the Caecum and Colon
      of Certain Mammals.

PMID- 17231539
TI  - Observations on Rickets, &c., in Wild Animals.

PMID- 17231541
TI  - On the "Invisible Blood Corpuscle" of Norris.

PMID- 17231543
TI  - On the Nature and Action of Certain Ligaments.

PMID- 17231542
TI  - On the Eye of Ornithorhynchus Paradoxus.

PMID- 17231544
TI  - Researches into the Histology of the Central Grey Substance of the Spinal Cord,
      Medulla Oblongata, and Pons Varolii: Part IV.

PMID- 17231545
TI  - Variations of the Thoracic Duct Associated with Abnormal Arterial Distribution.

PMID- 17231547
TI  - Notes on the Minute Structure of the Spinal Cord of a Human Foetus.

PMID- 17231546
TI  - On the Ferments or Enzymes of the Digestive Tract in Fishes.

PMID- 17231549
TI  - Anatomical Notices.

PMID- 17231548
TI  - Contributions to the Study of Nucleus-Division, based on the Study of Prickle
      Cells.

PMID- 17231550
TI  - Delineation of Skulls by Composite Photography.

PMID- 17231552
TI  - Case of Abnormal Development of the Coronary Arteries of the Heart.

PMID- 17231551
TI  - Repair of Wounds and Fractures in Aged Persons.

PMID- 17231553
TI  - Abnormal Ureters.

PMID- 17231554
TI  - Comparative Variability of Bones and Muscles, with Remarks on Unity of Type in
      Variations of the Origin and Insertion of Certain Muscles in Species unconnected
      by Unity of Descent.

PMID- 17231556
TI  - Nature of Ligaments: Part II.

PMID- 17231555
TI  - Congenital Malformation of the Trachea of a Horse.

PMID- 17231557
TI  - Osteology of Numenius longirostris, with Notes upon the Skeletons of other
      American Limicolae.

PMID- 17231558
TI  - Anatomy of Acquired Flat-Foot.

PMID- 17231559
TI  - New Method of Cutting Sections for Microscopical Examination.

PMID- 17231560
TI  - New Method of Demonstrating Scheiner's Experiment.

PMID- 17231562
TI  - Histology of the Vitreous Humour.

PMID- 17231561
TI  - Abnormal Disposition of the Colon.

PMID- 17231563
TI  - Oviduct in an Adult Male Skate.

PMID- 17231564
TI  - On the Influences of some Conditions on the Metamorphosis of the Blow-Fly (Musca
      vomitoria).

PMID- 17231565
TI  - On the Sources and the Excretion of Carbonic Acid at the Liver.

PMID- 17231566
TI  - A Method of Maceration: Being a Description of the Method in use at the Owens
      College, Manchester.

PMID- 17231567
TI  - Floating Kidney.

PMID- 17231568
TI  - The Movements of the Ulna in Rotation of the Fore-Arm.

PMID- 17231569
TI  - Dissection of a Double Monster (Epignathus).

PMID- 17231570
TI  - The Relation of the Alveolar form of Cleft Palate to the Incisor Teeth and the
      Intermaxillary Bones.

PMID- 17231571
TI  - The Dumb-Bell Shaped Bone in the Palate of Ornithorhynchus compared with the Pre
      nasal Bone of the Pig.

PMID- 17231572
TI  - The Infra-Orbital Suture.

PMID- 17231574
TI  - Anatomical Notices.

PMID- 17231573
TI  - Additional Note on the Oviducts of the Greenland Shark (Loemargus borealis).

PMID- 17231575
TI  - Diseases of the Reproductive Organs in Frogs, Birds, and Mammals.

PMID- 17231576
TI  - Movements of the Ulna in Rotation of the Fore-Arm.

PMID- 17231578
TI  - Supernumerary Cervico-Dorsal Vertebra-Bearing Ribs, with Vertebral and Costal
      Asymmetry; Abnormal Articulation in a Sternum.

PMID- 17231577
TI  - The Nature of Ligaments: Part III.

PMID- 17231579
TI  - Some Points in the Histology of the Medulla Oblongata, Pons Varolii, and
      Cerebellum: Part V.

PMID- 17231580
TI  - The External Auditory Meatus in the Child.

PMID- 17231581
TI  - The Relations of the Larynx and Trachea to the Vertebral Column in the Foetus and
      Child.

PMID- 17231582
TI  - A Rare Abnormality of the Pancreas.

PMID- 17231583
TI  - The Existence of a Fourth Species of the Genus Balaenoptera.

PMID- 17231584
TI  - Some Variations in the Anatomy of the Human Liver.

PMID- 17231585
TI  - Some Observations in Reference to Bilateral Asymmetry of Form and Function.

PMID- 17231587
TI  - The Musculus Sternalis and its occurrence in (Human) Anencephalous Monsters.

PMID- 17231586
TI  - Case of Exostosis of the Ulna.

PMID- 17231588
TI  - The Venous System of the Bladder and its Surroundings.

PMID- 17231590
TI  - Anatomical Notices.

PMID- 17231589
TI  - Notes on Some Unusual Variations in Human Anatomy.

PMID- 17231591
TI  - Development of the Blood Corpuscles in the Embryo of Perca Fluviatilis.

PMID- 17231592
TI  - An Account of some Recent Experiments on the Effects of very Low Temperatures on
      the Putrefactive Process, and on some Vital Phenomena.

PMID- 17231593
TI  - Accessory Lobe to the Left Lung.

PMID- 17231594
TI  - A Case of Abnormal Development of the Reproductive Organs of the Frog.

PMID- 17231595
TI  - Rotation and Circumduction.

PMID- 17231596
TI  - On the Movements of the Ulna in Pronation and Supination.

PMID- 17231597
TI  - The Anatomy of a Hydromicrocephalous Brain.

PMID- 17231598
TI  - On the Corpus Callosum in the Adult Human Brain.

PMID- 17231600
TI  - On the Hyomandibular Clefts and Pseudobranchs of Lepidosteus and Amia.

PMID- 17231599
TI  - Tumours in Animals.

PMID- 17231601
TI  - Anatomy of Spina Bifida.

PMID- 17231603
TI  - Tarsus and Carpus.

PMID- 17231602
TI  - Notes on Some Variations of the Shoulder-Muscles.

PMID- 17231604
TI  - The Blood-Forming Organs and Blood-Formation: An Experimental Research: Part I.

PMID- 17231605
TI  - The Relationship of Urea Formation to Bile Secretion: An Experimental Research:
      Part I.

PMID- 17231606
TI  - The Index of the Pelvic Brim as a Basis of Classification.

PMID- 17231607
TI  - Anatomy of Sowerby's Whale.

PMID- 17231609
TI  - A Second Bursa connected with the Insertion of the Biceps, and on some Rare
      Abnormalities.

PMID- 17231608
TI  - Two Cases of an Abnormal Coronary Artery of the Heart Arising from the Pulmonary
      Artery: With some Remarks upon the Effect of this Anomaly in producing Cirsoid
      Dilatation of the Vessels.

PMID- 17231610
TI  - Abnormalities of the Lobes of the Human Lung.

PMID- 17231611
TI  - The Nature of Ligaments: Part IV.

PMID- 17231612
TI  - Vital Relations of Micro-Organisms to Tissue Elements.

PMID- 17231613
TI  - The Anatomy of the Muscles, Ligaments, and Fasclae of the Orbit, including an
      Account of the Capsule of Tenon, the Check Ligaments of the Recti, and the
      Suspensory Ligaments of the Eye.

PMID- 17231614
TI  - Morphology of the Arterial System in Man: Part I.

PMID- 17231615
TI  - Anatomy of the Shoulder and Upper Arm of the Mole (Talpa europoea).

PMID- 17231616
TI  - Reproduction of the Carapax in Tortoises.

PMID- 17231617
TI  - Development and Decay of the Pigment Layer in Birds' Eggs.

PMID- 17231619
TI  - Skeleton in Geococcyx.

PMID- 17231618
TI  - Connection of the Os Odontoideum with the Body of the Axis Vertebra.

PMID- 17231620
TI  - The Relationship of Urea Formation to Bile Secretion: An Experimental Research:
      Part II.

PMID- 17231622
TI  - Sacral Index in Various Races of Mankind.

PMID- 17231621
TI  - Recent Histological Methods.

PMID- 17231623
TI  - Blood-Forming Organs and Blood-Formation: An Experimental Research: Part II.

PMID- 17231624
TI  - Malformations of Pelvis and Pelvic Organs in a Foetus.

PMID- 17231625
TI  - Anomalous Muscle in the Front of the Neck in a Human Subject-A Sterno
      Petrosopharyngeus.

PMID- 17231626
TI  - Case of Congenital Hypertrophy of the Leg. (Diffuse Venous Naevus.).

PMID- 17231627
TI  - Mandibular Dentition of the Shrews.

PMID- 17231628
TI  - Action of Infused Beverages on Peptic Digestion.

PMID- 17231629
TI  - Some Variations in the Human Skeleton.

PMID- 17231630
TI  - Note on a Case of Bicipital Rib.

PMID- 17231631
TI  - Osteology of Conurus Carolinensis.

PMID- 17231632
TI  - A Navajo Skull.

PMID- 17231633
TI  - Note on the Navajo Indian Skull.

PMID- 17231634
TI  - Origin of Certain Cysts-Ovarian, Vaginal, Sacral, Lingual, and Tracheal.

PMID- 17231635
TI  - The Blood-Forming Organs and Blood-Formation: An Experimental Research.

PMID- 17231636
TI  - Investigations in the Relation between Convergence and Accommodation of the Eyes.

PMID- 17231637
TI  - A Contribution to Splenic Histology.

PMID- 17231638
TI  - Supernumerary Leg in a Male Frog (Rana palustris).

PMID- 17231639
TI  - The Nature of the Relationship between Urea Formation and Bile Secretion.

PMID- 17231640
TI  - Hind Limb of Ichthyosaurus, and on the Morphology of Vertebrate Limbs.

PMID- 17231641
TI  - The Lumbar Curve of the Spinal Column in Several Races of Men.

PMID- 17231643
TI  - Physiology of the Heart of the Alligator.

PMID- 17231642
TI  - Anatomical Notices.

PMID- 17231644
TI  - Functions of the Tonsils.

PMID- 17231645
TI  - Investigations in the Relation between Convergence and Accommodation of the Eyes.

PMID- 17231646
TI  - Six Specimens of Spina Bifida with Bony Projections from the Bodies of the
      Vertebrae into the Vertebral Canal.

PMID- 17231647
TI  - Pentadactylus Pes in the Dorking Fowl, a Variety of the Gallus domesticus, with
      Especial Reference to the Hallux.

PMID- 17231648
TI  - Vitality of Wild Animals under Fire.

PMID- 17231649
TI  - Alimentary Canal and Pancreas of Acipenser, Amia, and Lepidosteus.

PMID- 17231650
TI  - Neural Spines of the Cervical Vertebrae as a Race-Character.

PMID- 17231651
TI  - Variations in the Nerve Supply of the Flexor Brevis Pollicis Muscle.

PMID- 17231652
TI  - Morphology of the Intrinsic Muscles of the Little Finger, with some Observations
      on the Ulnar Head of the Short Flexor of the Thumb.

PMID- 17231653
TI  - Nature of the Relationship of Urea Formation to Bile Secretion.

PMID- 17231655
TI  - Anatomico-Physiological Notices.

PMID- 17231654
TI  - Blood-Forming Organs and Blood-Formation: An Experimental Research.

PMID- 17231656
TI  - Rhythm and Innervation of the Heart of the Sea-Turtle.

PMID- 17231657
TI  - Osteological Note upon the Young of Geococcyx californianus.

PMID- 17231658
TI  - Myology of the Limbs of Dasyurus viverrinus.

PMID- 17231659
TI  - Intra-Peritoneal Blood-Transfusion, and the Fate of Absorbed Blood.

PMID- 17231660
TI  - Nerve Supply of Musculus Sternalis.

PMID- 17231661
TI  - Flat-Foot and Plantar Arch: A Lecture Delivered at Cambridge.

PMID- 17231662
TI  - Naegele Pelvis.

PMID- 17231663
TI  - A New Theory of Hearing.

PMID- 17231664
TI  - Investigations in the Relation between Convergence and Accommodation of the Eyes.

PMID- 17231665
TI  - Apparatus for Tracing Orthogonal Projections of the Skull in the United States
      Army Medical Museum.

PMID- 17231666
TI  - Action of Benzoyl-Ecgonin.

PMID- 17231668
TI  - Skull of a Navajo Child.

PMID- 17231667
TI  - Ossicle occasionally found on the Posterior Border of the Astragalus.

PMID- 17231669
TI  - Case of Double Superior Vena Cava with Left-sided Arrangement of the Azygos
      Veins.

PMID- 17231671
TI  - Anterior Belly of the Digastric Muscle of both Sides, arising from the Lower
      Border of the Horizontal Ramus of the Inferior Maxillary Bone.

PMID- 17231670
TI  - Deficiency of the Left Half of a Dorsal Vertebra.

PMID- 17231672
TI  - Brain in a Case of Motor Aphasia with Deafness.

PMID- 17231673
TI  - Man's Lost Incisors.

PMID- 17231675
TI  - The Position and Peritoneal Relations of the Mammalian Ovary.

PMID- 17231674
TI  - Rare Abnormality of the Large Arteries of the Heart.

PMID- 17231676
TI  - Some Monstrosities in a Dorking Fowl.

PMID- 17231677
TI  - The Vestigial Structures of the Reproductive Apparatus in the Male of the Green
      Lizard.

PMID- 17231678
TI  - The Morphology of the Mammalian Coracoid.

PMID- 17231679
TI  - The Myology of the Limbs of Dasyurus viverrinus.

PMID- 17231680
TI  - The Behaviour of Bacteria in the Digestive Tract.

PMID- 17231681
TI  - Some Thoughts on the Evolution and Affinity of Disease.

PMID- 17231682
TI  - Intra-Peritoneal Blood Transfusion, the Fate of Absorbed Blood: An Experimental
      Research.

PMID- 17231683
TI  - Branchial Fistulae, Cysts, Diverticula, and Supernumerary Auricles.

PMID- 17231685
TI  - A Gluteal Trochanter in the Human Subject.

PMID- 17231684
TI  - Absorption from the Mucous Membrane of the Urinary Bladder.

PMID- 17231686
TI  - Some Abnormalities of the Muscles of the Upper Limb.

PMID- 17231687
TI  - Anatomical Notices.

PMID- 17231688
TI  - Action of Infused Beverages on the Peptic and Pancreatic Digestion of the Chief
      Dietetic Proximate Principles.

PMID- 17231689
TI  - Relations of the Mammalia to the Ichthyopsida and Sauropsida.

PMID- 17231691
TI  - Menstruation-Its Nerve Origin-Not a Shedding of Mucous Membrane.

PMID- 17231690
TI  - Changes Produced in the Lungs of Sheep by a Parasitic Worm (Strongylus filaria).

PMID- 17231692
TI  - Remarkable Example of the Manner in which Pressure Changes in the Skeleton may
      Reveal the Labour History of the Individual.

PMID- 17231693
TI  - Morphology of the Sacral Plexus in Man.

PMID- 17231694
TI  - Behaviour of Bacteria in the Digestive Tract.

PMID- 17231695
TI  - Double Superior Vena Cava, Right Pulmonary Veins opening into the Right Auricle,
      and a Special Inter-auricular Foramen.

PMID- 17231697
TI  - Intra-Peritoneal Blood Transfusion, and the Fate of Absorbed Blood: An
      Experimental Research.

PMID- 17231696
TI  - Method of Combining Weigert's Haematoxylene-Copper Stain for Nerve Fibre with the
      Use of the Freezing Microtome.

PMID- 17231698
TI  - Variability in Human Structure as Displayed in Different Races of Men, with
      Especial Reference to the Skeleton.

PMID- 17231699
TI  - Remarks on the Conditions, Habits, Family History, &c., of Centenarians.

PMID- 17231700
TI  - Effects of Vaccination, and Subsequent Amputation of Supernumerary Fingers.

PMID- 17231701
TI  - Two Cases of Single Kidney.

PMID- 17231702
TI  - Some Variations in the Arrangements of the Nerves of the Human Body.

PMID- 17231704
TI  - Abbe's Apochromatic Micro-Objectives and Compensating Eye-Pieces.

PMID- 17231703
TI  - Notes on the Nervous Supply of the Musculus Sternalis.

PMID- 17231705
TI  - Contributions to the Comparative Craniology of the North-American Indians: The
      Skull in the Apaches.

PMID- 17231706
TI  - An Apparatus for Determining the Angle of Torsion of the Humerus.

PMID- 17231707
TI  - Account of Two Spines with Cervical Ribs, one of which has a Vertebra suppressed,
      and Absence of the Anterior Arch of the Atlas.

PMID- 17231708
TI  - Case of Misplaced Kidney, with Undescended Testicle and Rudimentary Vas Deferens
      on the Same Side.

PMID- 17231710
TI  - A Tumour weighing over Three Pounds, occurring in an Eighth Month Foetus.

PMID- 17231709
TI  - The Senses of Savages.

PMID- 17231711
TI  - Variations in the Nerve Supply of the Lumbrical Muscles in the Hand and Foot,
      with some Observations on the Innervation of the Perforating Flexors.

PMID- 17231712
TI  - The Causation of Several Variations and Congenital Abnormalities in the Human
      Skeleton.

PMID- 17231713
TI  - The Limb Plexuses of Mammals.

PMID- 17231714
TI  - The Development and Transition of the Testis, Normal and Abnormal.

PMID- 17231715
TI  - An Account of Two Rare Tumours connected with the Teeth: I. Odontome Radiculaire;
      II. Dentigerous Cyst.

PMID- 17231716
TI  - Curious Dropsical Condition of an Axolotl.

PMID- 17231717
TI  - Note Concerning the Endothelium of the Small Cerebral Arteries.

PMID- 17231718
TI  - A Coraco-Clavicular Sternal Muscle.

PMID- 17231719
TI  - Abnormal Muscle of the Hand.

PMID- 17231720
TI  - Anatomical Society of Great Britain and Ireland.

PMID- 17231721
TI  - Physiology of the Heart of the Snake.

PMID- 17231722
TI  - New Form of Recording Apparatus for the Use of Practical Physiology Classes.

PMID- 17231723
TI  - A New Model for Demonstrating the Action of the Muscles of the Eye-Ball.

PMID- 17231724
TI  - Anatomy of a Megaptera Longimana: Part I.

PMID- 17231725
TI  - Myology of Erithizon epixanthus.

PMID- 17231726
TI  - Notes from the Physiological Laboratory of the University of Edinburgh.

PMID- 17231727
TI  - Important Factor in the Causation of Some of the Curves which Develop in
      Mollities Ossium, Rickets, and Osteitis Deformans.

PMID- 17231728
TI  - A Critical Study in Cranial Morphology.

PMID- 17231729
TI  - Development and Transition of the Testis, Normal and Abnormal.

PMID- 17231730
TI  - Short Muscles of the Pollex and Hallux of the Anthropoid Apes, with Special
      Reference to the Opponens Hallucis.

PMID- 17231731
TI  - Structure and Development of the Ovum in an Annelid (Eudrilus).

PMID- 17231733
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231732
TI  - Muscular Abnormalities.

PMID- 17231734
TI  - Histology of the Skin of the Horse.

PMID- 17231735
TI  - The Observation of the Pupil as a Guide in the Administration of Chloroform.

PMID- 17231736
TI  - An Account of Some Experiments which show that Fibrin-Ferment is Absent from
      Circulating Blood.

PMID- 17231737
TI  - Comparative Data from 2000 Indian Crania in the United States Army Medical
      Museum.

PMID- 17231738
TI  - Can the Existence of a Tendency to Change in the Form of the Skeleton of the
      Parent result in the Actuality of that Change in the Offspring?

PMID- 17231739
TI  - The Pharmacology of the Nitrites and Nitro-Glycerine.

PMID- 17231740
TI  - Anatomy of a Megaptera longimana: Part II.

PMID- 17231741
TI  - Variations in the Hippocampus Major and Eminentia Collateralis in the Human
      Brain.

PMID- 17231742
TI  - The Arteries Forming the Circle of Willis.

PMID- 17231743
TI  - The Innervation of Axillary Muscular Arches in Man, with Remarks on their
      Homology.

PMID- 17231744
TI  - The Pineal Body (Epiphysis Cerebri) in the Brains of the Walrus and Seals.

PMID- 17231745
TI  - Abnormal Distribution of Arteries and Veins in the Neck.

PMID- 17231746
TI  - The Tongue and Gustatory Organs of Fiber zibethicus.

PMID- 17231747
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231748
TI  - The Pharmacology of the Nitrites and Nitro-Glycerine.

PMID- 17231749
TI  - The Morphology of the Vagus Nerve.

PMID- 17231750
TI  - The Musculus Sternalis.

PMID- 17231752
TI  - Account of a Teratoma springing from the Sphenoid of a Calf, with the Results
      produced by the Tumour.

PMID- 17231751
TI  - The Movements of the Ankle-Joint.

PMID- 17231753
TI  - Schema of the Circulation of the Blood and Lymph.

PMID- 17231754
TI  - Anatomy of a Megaptera Longimana: Part III.

PMID- 17231755
TI  - Development and Transition of the Testis, Normal and Abnormal.

PMID- 17231756
TI  - Microscopical Examination of Clarke's Column in Man, the Monkey, and the Dog.

PMID- 17231757
TI  - Note on the Action of the Ureters as observed during an Operation for the Removal
      of an Abdominal Tumour.

PMID- 17231759
TI  - On the Skeleton in the Genus Sturnella, with Osteological Notes upon other North
      American Icteridoe, and the Corridoe.

PMID- 17231758
TI  - Note on a Method of Preserving Blood-Corpuscles for Microscopical Examination.

PMID- 17231760
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231761
TI  - Development and Transition of the Testis, Normal and Abnormal.

PMID- 17231762
TI  - Nature of Ligaments: Part V.

PMID- 17231763
TI  - Comparison of the Convolutions of the Seals and Walrus with those of the
      Carnivora, and of Apes and Man.

PMID- 17231764
TI  - Morphological Changes that Occur in the Human Blood during Coagulation.

PMID- 17231766
TI  - Some Points in the Anatomy of a Megaptera Longimana: Part III.

PMID- 17231765
TI  - Anatomy and Physiology of the Shoemaker.

PMID- 17231767
TI  - Anatomy of the Papilla Foliata of the Human Infant.

PMID- 17231768
TI  - Epiphysis Cerebri in Petromyzon Fluviatilis.

PMID- 17231769
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231771
TI  - The Rectum and Anus.

PMID- 17231770
TI  - Comparative Osteology of Arctic and Sub-Arctic Water-Birds: Part I.

PMID- 17231772
TI  - Growth-Rate of the Bones of the Lower Extremities, with Especial Reference to
      Ricketty Curvatures.

PMID- 17231773
TI  - Anatomy of a Megaptera longimana: Part III.

PMID- 17231774
TI  - Effect of Chronic Disease of the Valves of the Heart upon the Sound Orifices, the
      Cavities, and the Walls.

PMID- 17231775
TI  - New Acid found in Human Urine which Darkens with Alkalies (Alcaptonuria).

PMID- 17231776
TI  - Notes on the Limb Myology of Procyon cancrivorus and of the Ursidoe.

PMID- 17231777
TI  - Anatomy of Hyoena striata: Part I.

PMID- 17231778
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231779
TI  - Comparative Osteology of Arctic and Sub-Arctic Water-Birds: Part II.

PMID- 17231780
TI  - Anatomy of Hyoena striata: Part II.

PMID- 17231781
TI  - Gustatory Organs of Vulpes vulgaris.

PMID- 17231782
TI  - Homology and Innervation of the Achselbogen and Pectoralis Quartus, and the
      Nature of the Lateral Cutaneous Nerve of the Thorax.

PMID- 17231783
TI  - Observations on the Earlier Stages in the Development of the Lungs of Rats and
      Mice.

PMID- 17231784
TI  - Hexadactylism, with especial Reference to the Signification of its Occurrence in
      a Variety of the Gallus domesticus.

PMID- 17231785
TI  - Construction of the Ventricles in the Mammalian Heart.

PMID- 17231787
TI  - Rabbit with an Intra-narial Epiglottis, with a Suggestion concerning the
      Phylogeny of the Mammalian Respiratory Apparatus.

PMID- 17231786
TI  - The Nature of Ligaments: Part VI.

PMID- 17231788
TI  - The Angle of the Neck with the Shaft of the Femur at Different Periods of Life
      and under Different Circumstances.

PMID- 17231790
TI  - External Auricular Opening and External Auditory Meatus in the Greenland-Right
      Whale, Baloena mysticetus.

PMID- 17231789
TI  - Position of the Mammalian Limb; regarded in the Light of Its Innervation and
      Development.

PMID- 17231791
TI  - Musculus Sternalis and its Nerve-Supply.

PMID- 17231792
TI  - Anatomy of a Megaptera longimana: Part IV.

PMID- 17231793
TI  - The Limits of Hearing.

PMID- 17231794
TI  - Abnormal Arrangement of the Kidney and its Vessels.

PMID- 17231796
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231795
TI  - Accessory Phrenic Nerve.

PMID- 17231797
TI  - Relations between the Superficial Origins of the Spinal Nerves from the Spinal
      Cord and the Spinous Processes of the Vertebrae.

PMID- 17231799
TI  - Abnormal Distribution of the Nerve to the Quadratus Femoris in Man, with Remarks
      on its Significance.

PMID- 17231798
TI  - SUPRA-CLAVICULARIS MUSCLE.

PMID- 17231800
TI  - Anatomy of a Megaptera longimana: Part IV.

PMID- 17231802
TI  - Observations on the Angle of the Neck of the Thigh-Bone.

PMID- 17231801
TI  - Observations on the Anatomy of the Prostate.

PMID- 17231803
TI  - Origin of Double Monstrosity.

PMID- 17231804
TI  - Contributions to the Comparative Osteology of Arctic and Sub-Arctic Water-Birds:
      Part III.

PMID- 17231805
TI  - Minute Anatomy of the Vagus Nerve in Selachians, with Remarks on the Segmental
      Value of the Cranial Nerves.

PMID- 17231806
TI  - Note on an Amylolytic Ferment found in the Gastric Mucous Membrane of the Pig.

PMID- 17231807
TI  - Experiments in Cranio-Cerebral Topography.

PMID- 17231808
TI  - Additional Observations on the Stomach in the Ziphioid and Delphinoid Whales.

PMID- 17231809
TI  - Loose Bodies in Joints.

PMID- 17231810
TI  - Unusual Arrangement of the Psoas Muscle.

PMID- 17231811
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231812
TI  - The Innervation of the Muscles of the Soft Palate.

PMID- 17231813
TI  - Absent Thoracic Duct causing OEdema of a Foetus.

PMID- 17231815
TI  - The Development of the Taste-Organs of Man.

PMID- 17231814
TI  - Contributions to the Comparative Osteology of Arctic and Sub-Arctic Water-Birds:
      Part IV.

PMID- 17231816
TI  - Notes of a Cardiac Neurotic.

PMID- 17231817
TI  - Additional Observations upon the Intra-narial Epiglottis.

PMID- 17231818
TI  - A Case of Congenital Absence of the Tibia.

PMID- 17231819
TI  - Observations upon the Mammalian Pharynx, with Especial Reference to the
      Epiglottis.

PMID- 17231821
TI  - The Placentation of Halicore Dugong.

PMID- 17231820
TI  - The Influence of Posture on the form of the Articular Surfaces of the Tibia and
      Astragalus in the different Races of Man and the Higher Apes.

PMID- 17231822
TI  - Tuberculosis in Vertebrates.

PMID- 17231824
TI  - Abnormal Development of Genito-Urinary System of Lepus Cuniculus.

PMID- 17231823
TI  - Notes of a Case of Persistent Left Superior Vena Cava, the Right Superior Vena
      Cava being in Great Part a Fibrous Cord.

PMID- 17231825
TI  - The Development of Diarthrodial Joints in Birds and Mammals.

PMID- 17231826
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland (with Index).

PMID- 17231827
TI  - The Proamnion and Amnion in the Chick.

PMID- 17231828
TI  - The Proportion of Bone and Cartilage in the Lumbar Section of the Vertebral
      Column of the Ape and Several Races of Men.

PMID- 17231829
TI  - The Occasional Eighth True Rib in Man and its Relation to Right Handedness.

PMID- 17231830
TI  - Further Observations on the Development of the Taste-Organs of Man.

PMID- 17231831
TI  - Abnormal Vascular Supply to the Liver.

PMID- 17231832
TI  - Two Cases of Variation in the Nerve-Supply of the First Lumbrical Muscle in the
      Hand.

PMID- 17231834
TI  - The Vertebral Column of a Young Gorilla.

PMID- 17231833
TI  - Observations on the Function of the Prostate Gland in Man and the Lower Animals:
      Part II.

PMID- 17231835
TI  - Further Observations on the Innervation of Axillary Muscles in Man.

PMID- 17231836
TI  - The Significance of the Third Trochanter and of Similar Bony Processes in Man.

PMID- 17231837
TI  - Some Vascular Anomalies observed during the Session 1888-89.

PMID- 17231838
TI  - The Flexors of the Digits of the Hand: I. The Muscular Masses in the Fore-Arm.

PMID- 17231839
TI  - The Gustatory Organs of Belideus ariel.

PMID- 17231840
TI  - Contributions to the Comparative Osteology of Arctic and Sub-Arctic Water-Birds:
      Part V.

PMID- 17231841
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231842
TI  - Intraparietal Sulcus of the Brain.

PMID- 17231843
TI  - Gustatory Organs of Procyon lotor.

PMID- 17231844
TI  - Dry Cover-Glass Microscopical Preparations.

PMID- 17231845
TI  - Hereditary Malformation of Digits.

PMID- 17231846
TI  - Contributions to the Comparative Osteology of Arctic and Sub-Arctic Water-Birds:
      Part VI.

PMID- 17231847
TI  - Stomach of the Narwhal: The Bearing of its Histology on Turner's and Max Weber's
      Nomenclature of the Stomach of the Ziphioid and Delphinoid Whales.

PMID- 17231848
TI  - Action of Various Stimuli on Non-Striped Muscle.

PMID- 17231849
TI  - Additional Note on the Influence of Posture on the Form of the Articular Surfaces
      of the Tibia and Astragalus in the Different Races of Man and the Higher Apes.

PMID- 17231850
TI  - Case of Hermaphroditism in a Common Frog (Rana temporaria).

PMID- 17231851
TI  - Anatomy of the Transversalis Muscle and its Relation to Inguinal Hernia.

PMID- 17231852
TI  - Spiracles of the Porbeagle Shark (Lamna cornubica).

PMID- 17231853
TI  - New Methods of Imbedding Fresh and Hardened Tissues.

PMID- 17231854
TI  - Prostate Gland: Its Enlargement or Hypertrophy: Part III.

PMID- 17231855
TI  - Note on the Transverse-Humeral, Coraco-Acromial, and Coraco-Humeral Ligaments,
      &c.

PMID- 17231856
TI  - The Cell Theory, Past and Present.

PMID- 17231857
TI  - Coagulation of Egg and Serum Albumen, Vitellin, and Serum Globulin, by Heat.

PMID- 17231858
TI  - Tumour in the Fresh-Water Mussel (Anodonta cygnea, Linn.).

PMID- 17231859
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231860
TI  - The Complete Fissures of the Human Cerebrum, and their Significance in Connection
      with the Growth of the Hemisphere and the Appearance of the Occipital Lobe.

PMID- 17231861
TI  - A Fermentation causing the Separation of Cystin: Preliminary Communication.

PMID- 17231862
TI  - The Orbito-Maxillary Frontal Suture in Man and Apes, with Notes on the Varieties
      of the Human Lachrymal Bone.

PMID- 17231863
TI  - Human Neck with the Odontoid Process distinct from the Body of the Axis Vertebra.

PMID- 17231864
TI  - A Contribution to the Pathology of Joint Bodies.

PMID- 17231866
TI  - Fibro-Plates and Intervertebral Discs.

PMID- 17231865
TI  - Abnormal Reproductive Organs in Rana temporaria.

PMID- 17231867
TI  - A Contribution to the Pharmacology of Curare and its Alkaloids: Part I.

PMID- 17231868
TI  - Variation in the Kidney of the Common Thornback (Raia clavata): its Nature,
      Range, and Probable Significance.

PMID- 17231870
TI  - Physical Notes on the Motion of the Blood in the Human Arteries.

PMID- 17231869
TI  - Case of Malformation of the Heart, with Large Deficiency in the Interauricular
      Septum, Patency of the Foramen Ovale and Stenosis of the Aortic Orifice.

PMID- 17231871
TI  - Injuries and Diseases of Nerves.

PMID- 17231872
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231873
TI  - Acromegaly, with the Description of a Skeleton.

PMID- 17231874
TI  - Histology of the Skin of the Elephant.

PMID- 17231875
TI  - Contribution to the Pathology of Retro-bulbar Neuritis.

PMID- 17231876
TI  - Contribution to the Pharmacology of Curare and its Alkaloids: Part II.

PMID- 17231877
TI  - Nature of the Giant-Cells of Tubercle and the Elements associated therewith, as
      seen in Comparative Pathology.

PMID- 17231878
TI  - Sternum as an Index of Sex, Height, and Age.

PMID- 17231879
TI  - Irregular Union of the First and Second Pieces of the Sternum in Man and Apes.

PMID- 17231880
TI  - Contributions to the Comparative Osteology of Arctic and Sub-Arctic Water-Birds:
      Part VII.

PMID- 17231881
TI  - Variations of the External Pterygoid Muscle.

PMID- 17231882
TI  - Fate of the Notochord and Development of the Intervertebral Disc in the Sheep,
      with Observations on the Structure of the Adult Disc in these Animals.

PMID- 17231883
TI  - Disposition of the Vertebral Column in Hanging (and Swinging) Postures.

PMID- 17231884
TI  - Note to Dr Hoorweg's Paper "Physical Notes on the Motion of the Blood in the
      Human Arteries".

PMID- 17231885
TI  - Pathology of Genu Valgum, or Knock-Knee.

PMID- 17231886
TI  - An Easy Method of Dissecting the Eyeball.

PMID- 17231887
TI  - Some Recent and some New Histological Methods.

PMID- 17231888
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231889
TI  - The Fissure of Rolando.

PMID- 17231890
TI  - Note on the Dissection of Flat-Foot.

PMID- 17231891
TI  - The Convolutions of the Brain: A Study in Comparative Anatomy.

PMID- 17231892
TI  - Note on a Tumour in Anodonta cygnea, Linn.

PMID- 17231893
TI  - Abnormal Arrangement of the Veins about the Popliteal Space.

PMID- 17231894
TI  - Malformation of the Female Organs of Generation-Vagina Duplex et Uterus Duplex
      Associated with Displacement of the Right Kidney.

PMID- 17231895
TI  - The Value of Nerve-Supply in the Determination of Muscular Homologies and
      Anomalies.

PMID- 17231896
TI  - Contribution to the Pharmacology of Curare and its Alkaloids: Parts III. and IV.

PMID- 17231897
TI  - Contributions to the Comparative Osteology of Arctic and Sub-Arctic Water-Birds:
      Part VIII.

PMID- 17231898
TI  - The Planes of Subperitoneal and Subpleural Connective Tissue, with their
      Connections.

PMID- 17231899
TI  - Abnormal Arrangement of the Ileo-Caecal Portion of the Intestine.

PMID- 17231900
TI  - Report of the Committee of Collective Investigation of the Anatomical Society of
      Great Britain and Ireland for the Year 1889-90.

PMID- 17231901
TI  - The Thyreo-Glossal Duct.

PMID- 17231902
TI  - Notes on the Origin of the Liver.

PMID- 17231903
TI  - The Means by which the Oily Debris in Catarrhal Nephritis is Removed.

PMID- 17231904
TI  - Dissection of a Symelian Monster.

PMID- 17231905
TI  - Some Points on the Surface Anatomy of the Brain: An Open Letter to Sir William
      Turner.

PMID- 17231907
TI  - Polymastism, with Special Reference to Mammae Erraticae and the Development of
      Neoplasms from Supernumerary Mammary Structures.

PMID- 17231906
TI  - Further Notes upon the Crania of North American Indians.

PMID- 17231908
TI  - Contributions to the Physiology and Pathology of the Blood: Part I.

PMID- 17231909
TI  - An Improved Method of Preparing Large Sections of Tissues for Microscopic
      Examination.

PMID- 17231910
TI  - Note on the Skin and Scalp of the Negro Foetus.

PMID- 17231911
TI  - The Sylvian Fissure and the Island of Reil in the Primate Brain.

PMID- 17231913
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231912
TI  - The Auditory Centre.

PMID- 17231914
TI  - Mode of Demonstrating the Gross Structure of the Eyeball.

PMID- 17231915
TI  - Simple Means of Explaining the Nature of Diplopia, &c.

PMID- 17231916
TI  - New Mode of Demonstrating the Relation of the Two Sides of the Retina to the
      Outer World.

PMID- 17231917
TI  - Note on a Spear Flag Indicator for Muscle-Nerve Demonstrations.

PMID- 17231918
TI  - Mode of Demonstrating the Developing Membranes in the Chick.

PMID- 17231919
TI  - Method by which Accurate Drawings may be Made by Amateurs.

PMID- 17231920
TI  - Note on the Muscles of the Rudimentary Ears-Pendants of the Neck-in Pigs.

PMID- 17231922
TI  - Double Chick Embryo.

PMID- 17231921
TI  - Mammary Variations per Defectum.

PMID- 17231923
TI  - Abnormal Arrangement of the Right Subclavian Artery in a Rabbit.

PMID- 17231924
TI  - Human Cerebrum with a Remarkably Modified Fronto-Parietal Lobe.

PMID- 17231925
TI  - Development of the Gyri and Sulci on the Surface of the Island of Reil of the
      Human Brain.

PMID- 17231926
TI  - Note on the Radio-Carpal Articulation.

PMID- 17231927
TI  - Contributions to the Physiology and Pathology of the Blood: Part II.

PMID- 17231928
TI  - Theory to Explain the Evolution of Warm-Blooded Vertebrates.

PMID- 17231929
TI  - Persistence of the Notochord in the Human Subject.

PMID- 17231930
TI  - Research into the Chemical Processes in the Small Intestine of Man.

PMID- 17231931
TI  - Some Points in the Anatomy of the Suboccipital Region.

PMID- 17231932
TI  - The Minute Anatomy of the Spinal Cord and Cerebellum Demonstrated by Golgi's
      Method.

PMID- 17231933
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231935
TI  - Double Right Parietal Bone in an Australian Skull.

PMID- 17231934
TI  - The Relations of the Dentary Arcades in the Crania of Australian Aborigines.

PMID- 17231936
TI  - Contributions to the Physiology and Pathology of the Blood: Part III.

PMID- 17231937
TI  - Observations on some Mammalian Taste-Organs.

PMID- 17231938
TI  - Contributions to the Comparative Osteology of Arctic and Sub-Arctic Water-Birds:
      Part IX.

PMID- 17231939
TI  - Variability in the Level of Attachment of the Lower Limb to the Vertebral Axis in
      Man.

PMID- 17231940
TI  - Observations on the Urinary Bladder and Urethra.

PMID- 17231941
TI  - The Occurrence of Haemoglobinuria in Blood-Pressure Experiments.

PMID- 17231942
TI  - Ossification in the Head of the Humerus at Birth.

PMID- 17231944
TI  - Some Applications of the above Method.

PMID- 17231943
TI  - Fusible Metal Injections.

PMID- 17231945
TI  - The Muscular Mechanism of Walking.

PMID- 17231946
TI  - Observations on a Mastitis Bacillus.

PMID- 17231947
TI  - On the Minute Anatomy of the Pes Hippocampi, by Dr Luigi Sala, and on Some
      General Anatomical Facts brought out by Golgi's Method.

PMID- 17231948
TI  - The Origin of the Cerebral Convolutions.

PMID- 17231949
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland (with Index);
      Proceedings of the Scottish Microscopical Society.

PMID- 17231950
TI  - Craniometry of some of the Outcaste Tribes of the Panjab.

PMID- 17231951
TI  - Occurrence of an Additional Phalanx in the Human Pollex.

PMID- 17231953
TI  - The Fossae round the Caecum, and the Position of the Vermiform Appendix, with
      Special Reference to Retro-Peritoneal Hernia.

PMID- 17231952
TI  - A Case of Transposition of the Thoracic and Abdominal Viscera with Congenital
      Malformation of the Heart and Certain Abnormalities of the Arterial and Venous
      Systems.

PMID- 17231954
TI  - Air-Bladder and Ear of British Clupeoid Fishes.

PMID- 17231955
TI  - Pectineus Muscle and its Nerve-Supply.

PMID- 17231956
TI  - Some Varieties of the Last Dorsal and First Lumbar Nerves.

PMID- 17231957
TI  - A Simple Method of Fixing Paraffin Sections to the Slide.

PMID- 17231958
TI  - A Pair of Supernumerary Teeth in the Molar Region.

PMID- 17231959
TI  - Direct Action of Hydrogen Sulphide, Hydrogen Selenide, and Hydrogen Telluride on
      Haemoglobin.

PMID- 17231960
TI  - Second Annual Report of the Committee of Collective Investigation of the
      Anatomical Society of Great Britain and Ireland for the Year 1890-91.

PMID- 17231961
TI  - Thyro-Glossal Duct or "Canal of His.".

PMID- 17231963
TI  - Congenital and Symmetrical Perforation of both Parietal Bones.

PMID- 17231962
TI  - The Comparative Anatomy of the Muscles and Nerves of the Superior and Inferior
      Extremities of the Anthropoid Apes: Part I.

PMID- 17231964
TI  - A Suggestion as to the Possible Cause of the Corona observed in certain After
      Images.

PMID- 17231966
TI  - Concerning the Taxonomy of the North American Pygopodes, based upon their
      Osteology.

PMID- 17231965
TI  - Complete Cervical Fistulae. A Note on C. F. Marshall's Paper on the Thyro-Glossal
      Duct or "Canal of His.".

PMID- 17231967
TI  - Experimental Pathological Evidence proving the Existence of Pancreatic Diabetes.

PMID- 17231969
TI  - The Position of the Epiglottis in Swallowing.

PMID- 17231968
TI  - The Repair of Bone, with special reference to Transplantation and other
      Artificial Aids.

PMID- 17231970
TI  - Bifurcation of the Femoral Artery with Subsequent Re-union.

PMID- 17231971
TI  - The Blood-Vessels of the Retina, with a Method of Preparation for Lantern
      Demonstration.

PMID- 17231972
TI  - On a Possible Obsolete Function of the Axillary and Pubic Hair Tufts in Man.

PMID- 17231973
TI  - Notes on some of the Viscera of Risso's Dolphin (Grampus griseus).

PMID- 17231975
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231974
TI  - The Minute Anatomy of the Central Nervous System, according to Golgi's Method.

PMID- 17231976
TI  - Myology of the Larynx.

PMID- 17231978
TI  - Cause of the Twisting of the Umbilical Cord, Illustrated by Mechanical Models.

PMID- 17231977
TI  - Note on Identical Malformations in Twins.

PMID- 17231979
TI  - Abnormal Arrangement of Arteries in the Region of the Kidney and Supra-Renal
      Body.

PMID- 17231980
TI  - Nutritive Importance of the Yolk Sac.

PMID- 17231981
TI  - Comparative Anatomy of the Muscles and Nerves of the Superior and Inferior
      Extremities of the Anthropoid Apes: Part II.

PMID- 17231982
TI  - Cerebral Hemispheres of Ornithorynchus paradoxus.

PMID- 17231983
TI  - A Few Applications of a Physical Theorem to Membranes in the Human Body in a
      State of Tension.

PMID- 17231984
TI  - Organ of Jacobson in the Kangaroo and Rock Wallaby (Macropus giganteus and
      Petrogale penicillata).

PMID- 17231985
TI  - Effect of Certain Drugs on the Reflex Excitability of the Spinal Cord.

PMID- 17231986
TI  - Gustatory Organs of Ateles ater.

PMID- 17231987
TI  - Method of Examining Blood, Bone, Marrow, &c.

PMID- 17231988
TI  - Pedal Skeleton of the Dorking Fowl, with Remarks on Hexadactylism and Phalangeal
      Variation in the Amniota.

PMID- 17231989
TI  - Notes upon the Shoulder Girdle of Certain Dicynodontoid Reptiles.

PMID- 17231990
TI  - Case of Abnormality of the Finger Nails.

PMID- 17231991
TI  - Research into the Nature and Action of the Enzymes produced by the Bacteria.

PMID- 17231992
TI  - Abnormal Position of Meckel's Diverticulum.

PMID- 17231993
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17231995
TI  - A Few Notes on Epithelial Pearls in Foetuses and Infants.

PMID- 17231994
TI  - Relations between the Weight of the Brain and its Parts, and the Stature and Mass
      of the Body, in Man.

PMID- 17231996
TI  - Adenoma of the Breast in Childhood.

PMID- 17231997
TI  - Sectional Anatomy of an Anencephalic Foetus.

PMID- 17231998
TI  - Relations of the Peritoneum to the Descending Colon in the Human Subject.

PMID- 17231999
TI  - A Racial Variation in the Length of the Palate Process of the Maxilla.

PMID- 17232000
TI  - A Plea for Uniformity in the Delimitation of the Regions of the Abdomen.

PMID- 17232001
TI  - Note on the Anatomy of the Suprarenal Bodies.

PMID- 17232002
TI  - Note on the Absence of the Subclavius Muscle.

PMID- 17232003
TI  - Cases of Meckel's Diverticulum.

PMID- 17232004
TI  - Additional Note on Bifurcation of the Femoral Artery.

PMID- 17232005
TI  - Macrodactyly, and some other Forms of Congenital Overgrowth, and their Relation
      to Tumours.

PMID- 17232006
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232007
TI  - The Costo-Sternal Articulations.

PMID- 17232008
TI  - The Integumentary Grooves on the Palm of the Hand and Sole of the Foot of Man and
      the Anthropoid Apes.

PMID- 17232009
TI  - The Articular Processes of the Vertebrae in the Gorilla compared with those in
      Man, and on Costo-Vertebral Variation in the Gorilla.

PMID- 17232011
TI  - The Brain of the late George Grote, F. R. S., with Comments and Observations on
      the Human Brain and its Parts generally.

PMID- 17232010
TI  - Extreme Anomaly of the Heart and Great Vessels.

PMID- 17232012
TI  - Contributions to the Craniology and Craniometry of Panjab Tribes.

PMID- 17232014
TI  - Contributions to the Histology of the Hedgehog (Erinaceus europoeus).

PMID- 17232013
TI  - The Cerebral Commissures in the Marsupialia and Monotremata.

PMID- 17232015
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232016
TI  - On the Occurrence of a Jacobson's Organ, with Notes on Development of Nasal
      Cavity, Lachrymal Duct, and Harderian Gland in Crocodilus porosus.

PMID- 17232017
TI  - Colloid in Lymphatics and Blood-Vessels of Thyroid in Goitre.

PMID- 17232018
TI  - Histology of the Hedgehog (Erinaceus europoeus).

PMID- 17232019
TI  - Relation of Dura Mater Surrounding Inferior Maxillary Nerve to Temporo-Maxillary
      Articulation.

PMID- 17232020
TI  - Unnamed Supernumerary Nasal Cartilages.

PMID- 17232021
TI  - Third Annual Report of Committee of Collective Investigation of Anatomical
      Society of Great Britain and Ireland for the Year 1891-92.

PMID- 17232022
TI  - Gastric Digestion of Proteids.

PMID- 17232024
TI  - The Suprasternal Bones in Man.

PMID- 17232023
TI  - Forked Nerve Endings on Hairs.

PMID- 17232025
TI  - Function of Urethral Bulb.

PMID- 17232026
TI  - Absence of Male Reproductive Organs in Two Hermaphrodite Molluscs.

PMID- 17232027
TI  - Congenital Absence of both Ulnae.

PMID- 17232028
TI  - Notes on Acromion.

PMID- 17232029
TI  - First Costo-Vertebral Joint.

PMID- 17232030
TI  - Delimitation of Regions of Abdomen.

PMID- 17232031
TI  - Origin of Ophthalmic Artery from Middle Meningeal.

PMID- 17232033
TI  - Delimitation of Regions of Abdomen.

PMID- 17232032
TI  - Complete Separation of Two Heads of Biceps Flexor Cruris Muscle.

PMID- 17232034
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232035
TI  - Comparative Osteological Notes on the Extinct Bird Ichthyornis.

PMID- 17232036
TI  - A Note on the Anatomy of the Hymen and on that of the "Posterior Commissure of
      the Vulva".

PMID- 17232037
TI  - The Myology of the Anencephalous Foetus.

PMID- 17232038
TI  - The Anatomy of Advanced Pregnancy in Macacus rhesus studied by Frozen Sections,
      by Casts and Microscopically.

PMID- 17232039
TI  - Morphology of Limb Arteries in Vertebrates, with Especial Reference to the
      Disposition in the Human Subject.

PMID- 17232040
TI  - On an Arrow-Poison from New Granada, and on its Botanical Source.

PMID- 17232041
TI  - The Adductor Muscles of the Thumb and Great Toe.

PMID- 17232042
TI  - Some Observations on the Temporal Bone, chiefly in Childhood.

PMID- 17232043
TI  - A Phrenic Nerve receiving a Root of Origin from the Descendens Hypoglossi.

PMID- 17232044
TI  - On the Rudimentary Hind-Limb of a Great Fin-Whale (Baloenoptera musculus) in
      Comparison with those of the Humpback Whale and the Greenland Right-Whale.

PMID- 17232045
TI  - Contributions to the Histology of the Hedgehog.

PMID- 17232046
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232047
TI  - Law of Transverse Vibrations of Strings applied to the Human Larynx.

PMID- 17232048
TI  - On Certain Early Malformations of the Embryo.

PMID- 17232049
TI  - Cystic Degeneration of the Heart, Spleen, Liver, and Kidneys.

PMID- 17232050
TI  - Case of Congenital Malformation of the Heart; with Transposition of the Aorta and
      Pulmonary Artery.

PMID- 17232051
TI  - The Structural Changes observed in the Testicles of Aged Persons.

PMID- 17232052
TI  - The Structural Changes in the Testicle of the Dog when it is Replaced within the
      Abdominal Cavity.

PMID- 17232053
TI  - Symmetrical Depressions on the Exterior Surface of the Parietal Bones (with Notes
      of Three Cases).

PMID- 17232054
TI  - On the Morphology of the Musculus Sternalis.

PMID- 17232055
TI  - Contributions to the Histology of the Hedgehog.

PMID- 17232056
TI  - Notes on the Development and Variations of the Atlas.

PMID- 17232058
TI  - Two Cases of Subdivision of the Pouch of Douglas in the Human Female into Three
      Fossae.

PMID- 17232057
TI  - On the Mammalian Pelvis, with Especial Reference to the Young of Ornithorhynchus
      Anatinus.

PMID- 17232059
TI  - Diverticulum (Meckel's) of Small Intestine.

PMID- 17232060
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232061
TI  - The Influence of Function, as Exemplified in the Morphology of the Lower
      Extremity of the Panjabi.

PMID- 17232062
TI  - Observations on the Appendix of the Testicle, and on the Cysts of the Epididymis,
      the Vasa Efferentia, and the Rete Testis.

PMID- 17232063
TI  - On the Structure of the Bone-Marrow in Relation to Blood-Formation.

PMID- 17232065
TI  - The Mammary Gland in a Gravid Porpoise (Phocoena Communis).

PMID- 17232064
TI  - The Physiological Characters of Carcinomata (Primary and Secondary).

PMID- 17232066
TI  - On some Conditions related to Double Monstrosity.

PMID- 17232068
TI  - On the Development of the Bones of the Foot of the Horse, and of Digital Bones
      Generally; and on a Case of Polydactyly in the Horse.

PMID- 17232067
TI  - Left Vena Cava Inferior.

PMID- 17232069
TI  - Fourth Annual Report of Committee of Collective Investigation of the Anatomical
      Society of Great Britain and Ireland for the Year 1892-93.

PMID- 17232070
TI  - Case of Lithopaedion.

PMID- 17232072
TI  - A Variety of Curara acting as a Muscle-Poison.

PMID- 17232071
TI  - The Origin and Distribution of the Nerves to the Lower Limb.

PMID- 17232073
TI  - The Ligaments of the Catarrhine Monkeys, with References to corresponding
      Structures in Man.

PMID- 17232074
TI  - The Origin and Distribution of the Nerves to the Lower Limb.

PMID- 17232075
TI  - Variations in the Position and Development of the Kidneys.

PMID- 17232076
TI  - Retained Testes in Man and in the Dog.

PMID- 17232077
TI  - The Condition of the Testes and Prostate Gland in Eunuchoid Persons.

PMID- 17232078
TI  - Three Projection Drawings of the Brain.

PMID- 17232079
TI  - The Development of the Skeleton of the Limbs of the Horse, with Observations on
      Polydactyly.

PMID- 17232080
TI  - The Development and Varieties of the Second Cervical Vertebra.

PMID- 17232081
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232082
TI  - Morphological Peculiarities in the Panjabi, and their Bearing on the Question of
      the Transmission of Acquired Characters.

PMID- 17232083
TI  - Axial Rotation of Abdominal Aorta, with Associated Abnormalities of the Branches.

PMID- 17232085
TI  - Varieties of Hydrocele of the Tunica Vaginalis Testis and some Anomalous States
      of the Processus Vaginalis.

PMID- 17232084
TI  - Musculus Saphenus.

PMID- 17232086
TI  - Case of Left Kidney Displaced and Immovable.

PMID- 17232088
TI  - Some Variations in the Foramen Ovale in the Heart of the Sheep.

PMID- 17232087
TI  - Unusual Malformation of the Heart.

PMID- 17232089
TI  - Abnormal Sternum.

PMID- 17232091
TI  - Note on the Supracostalis Anterior.

PMID- 17232090
TI  - The Foetus of Halicore Dugong and of Manatus Senegalensis: Part I.

PMID- 17232092
TI  - Notes on a Theory to account for the various Arrangements of the Flexor Profundus
      Digitorum in the Hand and Foot of Primates.

PMID- 17232093
TI  - Case of Single Unilateral Kidney.

PMID- 17232095
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232094
TI  - The Development of the Skeleton of the Limbs of the Horse, with Observations on
      Polydactyly: Part II.

PMID- 17232096
TI  - A Research into the Histological Structure of the Olfactory Organ.

PMID- 17232097
TI  - On the Urinogenital and Blood-Vascular Systems of a Rabbit possessed of a Single
      Kidney.

PMID- 17232098
TI  - On the Long Sensory Root of the Ciliary Ganglion as figured by Cloquet.

PMID- 17232100
TI  - On the Morphology of the Tendo-Achillis.

PMID- 17232099
TI  - Three Cases of Congenital Absence of the Whole or Part of a Bone.

PMID- 17232101
TI  - Microcephaly and Infantile Hemiplegia.

PMID- 17232102
TI  - Calcareous Body removed from the Bursa over the Patella.

PMID- 17232103
TI  - Puce Iron-Pigmented Renal Calculi.

PMID- 17232104
TI  - A Case of Absence of the Radial Artery.

PMID- 17232106
TI  - Abnormal Muscular Contractions and their Effects.

PMID- 17232105
TI  - Notice of an Instance of Maternal Impressions: A Letter addressed to Professor M
      ;Kendrick.

PMID- 17232107
TI  - Anatomical Notes.

PMID- 17232108
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland (with Index).

PMID- 17232109
TI  - The Central Connections and Relations of the Trigeminal, Vago-Glossopharyngeal,
      Vago-Accessory, and Hypoglossal Nerves.

PMID- 17232110
TI  - Histological Changes induced in Sympathetic, Motor, and Sensory Nerve Cells by
      Functional Activity (Preliminary note).

PMID- 17232111
TI  - Are the Extrinsic Muscles of the Air-bladder in some Siluroidae and the "Elastic
      Spring" Apparatus of others Subordinate to the Voluntary Production of Sounds?
      What is, according to our Present Knowledge, the Function of the Weberian
      Ossicles?: A Contribution to the Biology of Fishes.

PMID- 17232112
TI  - Abnormal Kidneys from the Domestic Pig (Sus scrofa).

PMID- 17232113
TI  - Case of Absence of the Right Kidney.

PMID- 17232114
TI  - A Nerve Piercing the Walls of an Artery.

PMID- 17232115
TI  - Osteology of certain Cranes, Rails, and their Allies, with Remarks upon their
      Affinities.

PMID- 17232116
TI  - Fifth Annual Report of the Committee of Collective Investigation of the
      Anatomical Society of Great Britain and Ireland for the Year 1893-94.

PMID- 17232117
TI  - Observations on the Urinary Bladder and Urethra: Part II. The Nerves.

PMID- 17232118
TI  - Some Rare Nerve and Muscle Anomalies, with Remarks on their Significance.

PMID- 17232120
TI  - Carpus of the Greenland Right-Whale (Baloena mysticetus) and of Fin-Whales.

PMID- 17232119
TI  - A Peculiar Arrangement of the Supra-scapular Vein.

PMID- 17232121
TI  - Chemistry and Coagulation of Milk.

PMID- 17232122
TI  - Contribution to the Morphology of the Prostate.

PMID- 17232123
TI  - Are the Extrinsic Muscles of the Air-bladder in some Siluroidae and the "Elastic
      Spring" Apparatus of others Subordinate to the Voluntary Production of Sounds?
      What is, according to our Present Knowledge, the Function of the Weberian
      Ossicles?: A Contribution to the Biology of Fishes.

PMID- 17232124
TI  - Note on an Injection Apparatus.

PMID- 17232125
TI  - Variations in the Form of the Thyroid Gland in Man.

PMID- 17232126
TI  - Inter- and Intra-Cellular Passages in the Liver of the Frog.

PMID- 17232127
TI  - Rudimentary Metacarpal and Metatarsal Bones of the Domestic Ruminants.

PMID- 17232128
TI  - Observations upon the Urinary Bladder and Urethra: Part III. Physiological.

PMID- 17232129
TI  - The Central Nervous System of an Anencephalous Foetus.

PMID- 17232130
TI  - Growth of Brain in Men and Monkeys, with a Short Criticism of the Usual Method of
      stating Brain-Ratios.

PMID- 17232131
TI  - The Microcephalic or Idiot Skull, and the Macrocephalic or Hydrocephalic Skull.

PMID- 17232132
TI  - An Unusual Mode and Site of Termination of the Right Sacral Sympathetic Cord.

PMID- 17232133
TI  - A Skull with Enormous Parietal Foramina.

PMID- 17232134
TI  - Adventitious Joint of the Femur following Ununited Fracture.

PMID- 17232135
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232136
TI  - Variations in Crania of Gorilla Savagei.

PMID- 17232137
TI  - The Effects of Electricity and Magnetism on Development.

PMID- 17232138
TI  - The Unsymmetrical Distribution of the Cranial Nerves of Fishes.

PMID- 17232140
TI  - The Extensibility of Muscle.

PMID- 17232139
TI  - The Structure of the Inferior Maxilla, with special reference to the position of
      the Inferior Dental Canal.

PMID- 17232141
TI  - The Semilunar Fibro-Cartilages and Transverse Ligament of the Knee-Joint.

PMID- 17232142
TI  - Are the Extrinsic Muscles of the Air-bladder in some Siluroidae and the "Elastic
      Spring" Apparatus of others Subordinate to the Voluntary Production of Sounds?
      What is, according to our Present Knowledge, the Function of the Weberian
      Ossicles?: A Contribution to the Biology of Fishes.

PMID- 17232143
TI  - On M. Dubois' Description of Remains recently found in Java, named by him
      Pithecanthropus erectus: With Remarks on so-called Transitional Forms between
      Apes and Man.

PMID- 17232144
TI  - The Movements of the Metacarpo-Phalangeal Joint of the Thumb.

PMID- 17232145
TI  - The Modes of Origin of the Carotid and Subclavian Arteries from the Arch of the
      Aorta in Some of the Higher Primates.

PMID- 17232146
TI  - Rare Abnormal Arrangement of the Cardiac Coronary Arteries.

PMID- 17232147
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232148
TI  - The Analysis of Voluntary Muscular Movements by Certain New Instruments.

PMID- 17232149
TI  - The Minute Structure of the Reticulum in the Cat's Spleen.

PMID- 17232150
TI  - The Presence of Scales in the Integument of Polyodon folium.

PMID- 17232151
TI  - The Obliquity of the Arm of the Female in Extension. The Relation of the Forearm
      with the Upper Arm in Flexion.

PMID- 17232152
TI  - The Morbid Anatomy of the Bones in Chronic Glanders in the Human Subject.

PMID- 17232153
TI  - The Morphology of the Oblique Radio-ulnar Ligament.

PMID- 17232154
TI  - An Unusually Large Terminal Vermiform Appendix, with Recurved Small Conical
      Caecum; with some remarks on the Peritoneal Pouches.

PMID- 17232156
TI  - Are the Extrinsic Muscles of the Air-bladder in some Siluroidae and the "Elastic
      Spring" Apparatus of others Subordinate to the Voluntary Production of Sounds?
      What is, according to our Present Knowledge, the Function of the Weberian
      Ossicles?: A Contribution to the Biology of Fishes.

PMID- 17232155
TI  - The Form of the Spleen and the Kidneys.

PMID- 17232157
TI  - Description of a Foetus the Subject of Retroflexion of the Trunk -Ectopia
      Viscerum and Spina Bifida; with a Discussion as to the cause of these Associated
      Abnormalities.

PMID- 17232158
TI  - The Popliteus Muscle.

PMID- 17232159
TI  - The Geniculate Articular Surfaces of the Femur and Tibia.

PMID- 17232160
TI  - The Tone and Curves of the Phonograph.

PMID- 17232162
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232161
TI  - The Form of the Sternum in the Greenland Right-Whale (Baloena mysticetus).

PMID- 17232163
TI  - Homoplasty of the Brain of Rodents, Insectivores, and Carnivores.

PMID- 17232164
TI  - Critical Note on Colour Vision.

PMID- 17232165
TI  - Note on the Stereophotochromoscope-a new Optical Instrument.

PMID- 17232166
TI  - External Characters and some Parts of the Anatomy of a Beluga (Delphinapterus
      leucas).

PMID- 17232167
TI  - Morphology of the True "Limbic Lobe," Corpus Callosum, Septum Pellucidum and
      Fornix.

PMID- 17232168
TI  - Anomalous Muscle of the Thorax connected with the Diaphragm.

PMID- 17232169
TI  - Clinical Value of the Four-Root Theory of the Cranial Nerves.

PMID- 17232170
TI  - Optic Nerve as Part of the Central Nervous System.

PMID- 17232171
TI  - Origin and Intra-Cranial Course of the Ophthalmic Artery, and the Relationship
      they bear to the Optic Nerve.

PMID- 17232172
TI  - Retinacula of Weitbrecht. What is their Function?

PMID- 17232173
TI  - Lymphadenoma (Hodgkin's Disease) of the Lymphatic Glands as a Distinct
      Pathological Affection.

PMID- 17232174
TI  - Nerve of Wrisberg.

PMID- 17232175
TI  - Organ of Jacobson in the Monotremata.

PMID- 17232176
TI  - Effects upon the Testes of Ligature of the Spermatic Artery, Spermatic Veins, and
      of both Artery and Veins.

PMID- 17232178
TI  - Morphology of the True "Limbic Lobe," Corpus Callosum, Septum Pellucidum and
      Fornix.

PMID- 17232177
TI  - Description of two Symelian Monsters.

PMID- 17232179
TI  - Interesting Abnormality of the Hepatic Artery, with Explanation of the Condition.

PMID- 17232180
TI  - Abnormal Distribution of the Nervus Dorsalis Scapulae, and of certain of the
      Intercostal Nerves.

PMID- 17232181
TI  - Abnormal Anterior Abdominal Vein in a Frog.

PMID- 17232182
TI  - Bile-Salts (Glyco- and Tauro-Cholate of Soda) in their Relation to the Secretion
      of Urea.

PMID- 17232183
TI  - Notes on the Anatomy of an Anencephalous Foetus having Three Arms and Three Lower
      Limbs.

PMID- 17232184
TI  - The Influence of a Previous Sire.

PMID- 17232185
TI  - A Variation that occurs in the Manubrium Sterni of Higher Primates.

PMID- 17232186
TI  - Further Notes on the Brain of Ornithorynchus paradoxus.

PMID- 17232187
TI  - Some Observations on the Topographical Anatomy of the Fourchette.

PMID- 17232188
TI  - The True Capsule of the Knee-Joint.

PMID- 17232189
TI  - Geniculate Articular Surfaces of the Femur and Tibia.

PMID- 17232190
TI  - Urinary Calculi: their Formation and Structure.

PMID- 17232191
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232192
TI  - Formation and Structure of the Optic Nerve, and its Relation to the Optic Stalk.

PMID- 17232193
TI  - Pancreas of the Hedgehog during Hibernation.

PMID- 17232194
TI  - Accessory Segment in the Pulmonary Valve.

PMID- 17232195
TI  - Studies in the Peritoneum: Its Arrangement in Animals.

PMID- 17232196
TI  - Case of Ectopia Vesicae, with Patent Vitelline Duct.

PMID- 17232197
TI  - Some Structures in the Elbow-Joint.

PMID- 17232198
TI  - Temporal Fossa.

PMID- 17232199
TI  - Processes of the Occipital and Mastoid Regions of the Skull.

PMID- 17232200
TI  - Astragalo-Calcaneo-Navicular Joint.

PMID- 17232201
TI  - Halichoerus grypus: The Grey Seal: Observations on its External Appearances and
      Visceral Anatomy.

PMID- 17232202
TI  - Homology of the Dumb-Bell-Shaped Bone in Ornithorhynchus.

PMID- 17232203
TI  - What is Sibson's Muscle (Scalenus pleuralis)?

PMID- 17232205
TI  - Note to Dr Elliot Smith's Paper on the Morphology of the True "Limbic Lobe," &c.

PMID- 17232204
TI  - Hereditary Polydactylism.

PMID- 17232207
TI  - The Structure of the Cerebral Hemisphere of Ornithorhynchus.

PMID- 17232206
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232208
TI  - Halichoerus Grypus: The Grey Seal: Observations on its External Appearances and
      Visceral Anatomy.

PMID- 17232209
TI  - Ossification of the Third Trochanter in Man.

PMID- 17232210
TI  - Note on an Oblique Interosseous Radio-Ulnar Ligament found in the Punjabi.

PMID- 17232211
TI  - Some Points in the Anatomy of a Sirenomelian Monster.

PMID- 17232212
TI  - The Mammalian Hyoid, with especial Reference to that of Lepus, Hyrax, and
      Choloepus.

PMID- 17232213
TI  - Occurrence of an Enormous Renal Calculus.

PMID- 17232214
TI  - A Discussion of some Points in the Distribution of the Spinal Nerves.

PMID- 17232215
TI  - A Case of Adrenal Adenoma.

PMID- 17232216
TI  - On the Structure of the Red Glands in the Swim-Bladder of certain Fishes: With a
      Note on their Possible Function.

PMID- 17232217
TI  - Large Cystic Myxoma attached to the Colon of the Sheep.

PMID- 17232218
TI  - Comparison of Anomalous Parts of Two Subjects, one with a Cervical Rib, the other
      with a Rudimentary First Rib: With Notes on the Cases.

PMID- 17232219
TI  - Another Heart with Moderator Band in Left Ventricle.

PMID- 17232221
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232220
TI  - Abnormalities of Muscles, Nerves, Heart, Vessels, and Ligaments.

PMID- 17232222
TI  - The Trinil Femur (Pithecanthropus erectus), contrasted with the Femora of Various
      Savage and Civilised Races.

PMID- 17232223
TI  - The Use of Colour Screens for Microphotography.

PMID- 17232224
TI  - The Platymeric, Pilastric, and Popliteal Indices of the Race Collection of Femora
      in the Anatomical Museum of the University of Edinburgh.

PMID- 17232225
TI  - The Sesamoid Bones of the Hand: a Skiagraphic Confirmation of the Work done by
      Pfitzner.

PMID- 17232226
TI  - The Late Sir George Murray Humphry, M.D., LL.D. &c.

PMID- 17232227
TI  - Preliminary Note on the Development of the Clitoris, Vagina, and Hymen.

PMID- 17232228
TI  - Note upon the Vibrational Rate of the Membranes of Recording Tambours.

PMID- 17232230
TI  - Some Points in the Anatomy of the Dorsum of the Hand, with special reference to
      the Morphology of the Extensor Brevis Digitorum Manus.

PMID- 17232229
TI  - Sixth Annual Report of the Committee of Collective Investigation of the
      Anatomical Society of Great Britain and Ireland, 1895-96.

PMID- 17232231
TI  - Certain Points in the Anatomy and Mechanism of the Wrist-Joint Reviewed in the
      Light of a Series of Rontgen Ray Photographs of the Living Hand.

PMID- 17232232
TI  - The ;Fornix Superior'.

PMID- 17232233
TI  - The Topographical Anatomy of the Spleen, Pancreas, Duodenum, Kidneys, &c:
      Illustrated by a Cast of these Viscera hardened In Situ.

PMID- 17232234
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232235
TI  - Abnormalities of the Middle Sacral Artery, and their Morphological Significance.

PMID- 17232236
TI  - The Haemolymph Glands of some Vertebrates.

PMID- 17232237
TI  - The Action of the Products of the Organism of Diphtheria on the Heart Muscle of
      the Frog (Rana temporaria): A Preliminary Note.

PMID- 17232238
TI  - An Investigation into some of the Principles of Auscultation: Part I.

PMID- 17232239
TI  - The Interpretation of the Phonograms of Vowels.

PMID- 17232240
TI  - The Genesis of Vowels.

PMID- 17232241
TI  - Post-Mortem Artificially Contracted Indian Heads.

PMID- 17232243
TI  - A Descriptive Account of the Genital Apparatus in the Boar and in the Pig.

PMID- 17232242
TI  - The Glands of the Ciliary Body.

PMID- 17232244
TI  - On the Occurrence of an apparently Distinct Prevomer in Gomphognathus.

PMID- 17232245
TI  - An apparently hitherto Undescribed Nasal Floor-Bone in the Hairy Armadillo.

PMID- 17232246
TI  - An Abnormal Muscle of the Hand, with Remarks on the Course of the Radial Artery.

PMID- 17232247
TI  - Variations of Ribs in the Primates, with especial reference to the Number of
      Sternal Ribs in Man.

PMID- 17232248
TI  - Notes on Certain Physical and Physiological Measurements and Estimates.

PMID- 17232249
TI  - Note on two Useful Accessories in Serial Section-Cutting by the Paraffin Method.

PMID- 17232250
TI  - Summary of a Paper entitled-"On the Variations in the Character of the
      Contractions of Striated Muscle with Periodic Stimulation of some Duration, and
      on Recovery of the Muscle.".

PMID- 17232252
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232251
TI  - PREFATORY NOTE.

PMID- 17232254
TI  - An Investigation into some of the Principles of Auscultation: Part II.

PMID- 17232253
TI  - Myology of Dolichotis Patagonica and Dasyprocta Isthmica.

PMID- 17232255
TI  - Note on the Reducing Power of the Tissues.

PMID- 17232256
TI  - Haematoporphyminuria and its Relations to the Source of Urobilin.

PMID- 17232257
TI  - Case of Polypus of the Pylorus, with Intussusception.

PMID- 17232258
TI  - Observations on the Histology of Medullated Nerve Fibres in Man and Rabbits,
      derived from a Study of their Pathological Anatomy.

PMID- 17232260
TI  - A Rare Condition of the Vermiform Appendix.

PMID- 17232259
TI  - Structure of Cross-Striated Muscle, and a Suggestion as to the Part I. Nature of
      its Contraction.

PMID- 17232261
TI  - Case of Complete Transposition of Viscera.

PMID- 17232262
TI  - On the Regeneration of Nerves.

PMID- 17232263
TI  - Notes on the Dissection of a Case of Double Knock-Knee.

PMID- 17232264
TI  - Structure and Contraction of Striped Muscular Fibre.

PMID- 17232265
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232266
TI  - The Action of Infused Beverages on Peptic and Pancreatic Digestion.

PMID- 17232267
TI  - The Existence of a Sterno-Coracoidal Articulation in a Foetal Marsupial.

PMID- 17232270
TI  - Case of an Additional Presacral Vertebra.

PMID- 17232269
TI  - Some Points in Comparative Myological Nomenclature.

PMID- 17232268
TI  - Notes on the Duodenum and the Pylorus.

PMID- 17232271
TI  - The Structure of Cross-Striated Muscle, and a Suggestion as to the Nature of its
      Contraction.

PMID- 17232272
TI  - The Rolandic and Calcarine Fissures-A Study of the Growing Cortex of the
      Cerebrum.

PMID- 17232273
TI  - Case of Anomalous Kidney and Ureter.

PMID- 17232274
TI  - Notes on the Myology of a Negro.

PMID- 17232276
TI  - Notes on the Dissection of a Third Negro.

PMID- 17232275
TI  - Replies to Questions Issued by the Anatomical Society of Great Britain and
      Ireland.

PMID- 17232278
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232277
TI  - An Experimental Research upon Cerebro-cortical Afferent and Efferent Tracts.

PMID- 17232279
TI  - Topographical Sketch of the Lateral Wall of the Pelvic Cavity, with Special
      Reference to the Ovarian Groove.

PMID- 17232280
TI  - A Modification of the Chrome Silver Method for Nerve Cells.

PMID- 17232281
TI  - The Insular District of the Cerebral Cortex in Man and in the Man-like Apes.

PMID- 17232282
TI  - On the Anatomy of Macropus rufus.

PMID- 17232283
TI  - Preliminary Note on the Structure and Function of the Epididymis and Vas Deferens
      in the Higher Mammalia.

PMID- 17232284
TI  - On the Structure and Morphology of the Intromittent Sac of the Male Guinea-Pig
      (Cavia cobaya).

PMID- 17232285
TI  - Endarteritis Proliferens.

PMID- 17232286
TI  - Seventh Report of the Committee of Collective Investigation of the Anatomical
      Society of Great Britain and Ireland, 1896-97.

PMID- 17232287
TI  - The Relation of the Fornix to the Margin of the Cerebral Cortex.

PMID- 17232288
TI  - Some Observations on the Structure of the Rectum.

PMID- 17232290
TI  - Case of Marked Distension of the Transverse and Descending Parts of the Colon.

PMID- 17232289
TI  - Abnormal Relation of the Vermiform Appendix to the Plica Vascularis, leading to
      Appendicitis.

PMID- 17232291
TI  - On a Pair of Negro Femora.

PMID- 17232292
TI  - Skiagraphy after Injection of the Blood-Vessels with Mercury.

PMID- 17232293
TI  - On a Functional Adaptation of Phagocytosis.

PMID- 17232294
TI  - Observations on the Development and Nutrition of Bone and Cartilage, and on the
      Relations of Connective Tissues to each other in Health and Disease.

PMID- 17232295
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232296
TI  - A Theory of Muscular Contraction.

PMID- 17232298
TI  - Abnormal Arrangement of the Spermatic Arteries and of the Right Cord and Testes.

PMID- 17232297
TI  - Anomalous Female Uro-Genital Organs.

PMID- 17232299
TI  - Case of Clavicular Insertion of the Pectoralis Minor.

PMID- 17232300
TI  - On the Linear Determination of the Human Tooth Form.

PMID- 17232301
TI  - The Apertura Pyriformis.

PMID- 17232302
TI  - Further Observations upon the Fornix, with Special Reference to the Brain of
      Nyctophilus.

PMID- 17232303
TI  - On the Nature of the Weigert-Pal Method.

PMID- 17232305
TI  - The Morphology of the Triangular Cartilage of the Wrist.

PMID- 17232304
TI  - Skull of an Adult Microcephalic Idiot.

PMID- 17232306
TI  - The Thymus Gland in the Marsupialia.

PMID- 17232307
TI  - Concerning the Parathyroid Glands: A Critical, Anatomical, and Experimental
      Study.

PMID- 17232308
TI  - The Sympathetic Innervation of the Aorta and Intercostal Arteries.

PMID- 17232309
TI  - The Limb Myology of Gymnura Rafflesii.

PMID- 17232311
TI  - The Causation of Brachy- and Dolicho-cephaly.

PMID- 17232310
TI  - A Case of Ectopia Cordis c. Fissura Sterni.

PMID- 17232313
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232312
TI  - A Case of Idiopathic Dilatation of the Sigmoid Colon and Rectum, accompanied by a
      Diaphragmatic Hernia of the Stomach.

PMID- 17232314
TI  - A Decorated Sculptured Human Skull from New Guinea.

PMID- 17232316
TI  - Moderator Band in Left Ventricle and Tricuspid Left Auriculo-Ventricular Valve.

PMID- 17232315
TI  - An Account of a Blastodermic Vesicle of the Sheep of the Seventh Day, with Twin
      Germinal Areas.

PMID- 17232317
TI  - Spontaneous Cure and Torsion of Aneurism in a Sheep.

PMID- 17232318
TI  - Concerning the Parathyroid Glands: A Critical, Anatomical, and Experimental
      Study.

PMID- 17232319
TI  - The Caudal Limit of the Lumbar Visceral Efferent Nerves in Man.

PMID- 17232320
TI  - On the Anatomical Structure of the Vagus Nerve.

PMID- 17232321
TI  - The Muscles of Mammals, with Special Relation to Human Myology: A Course of
      Lectures delivered at the Royal College of Surgeons of England.

PMID- 17232322
TI  - A Preliminary Investigation of the Influence of Body-Posture on the Position and
      Shape of Abdominal and Thoracic Organs.

PMID- 17232323
TI  - The Shape and Position of the Bladder in the Child.

PMID- 17232324
TI  - Natural Selection, as Shown in the Typical Speed-Skater.

PMID- 17232325
TI  - On the Arterial Arches and Great Veins in the Foetal Marsupial.

PMID- 17232327
TI  - On the Origin of Vertebrates, Deduced from the Study of Ammocoetes.

PMID- 17232326
TI  - The Correlated Distribution of Abdominal Pores and Nephrostomes in Fishes.

PMID- 17232328
TI  - The Genito-Urinary Organs of the Female Indian Elephant.

PMID- 17232329
TI  - The Development and Morphology of the Vascular System in Mammals. The Posterior
      End of the Aorta and the Iliac Arteries.

PMID- 17232330
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232331
TI  - The Salivary Digestion of Starch in Simple and Mixed Diets: An Experimental
      Inquiry.

PMID- 17232332
TI  - A Case of Crossed Dystopia of the Kidney, with Fusion.

PMID- 17232333
TI  - The Duodeno-Jejunal Flexure: Its Variations, and their Significance.

PMID- 17232334
TI  - Notes on a Series of Thirty-Nine Cases of Meckel's Diverticulum.

PMID- 17232335
TI  - Congenital Abnormalities of the Heart in the Insane.

PMID- 17232336
TI  - Note on a Case of Six Lumbar Vertebrae and Abnormal Middle Sacral Artery.

PMID- 17232337
TI  - Contributions to the Comparative Anatomy of the Neuroglia: Being Part of the
      Thesis for the Degree of Doctor of Medicine of Edinburgh University, July 1897.

PMID- 17232338
TI  - On the Organ of Jacobson in the Hyrax.

PMID- 17232339
TI  - Is there a Critical Period in Marsupial Development?

PMID- 17232341
TI  - A Note on Hereditary Stiffness of the Metacarpo-Phalangeal Joint of the Thumb.

PMID- 17232340
TI  - The Muscles of Mammals, with Special Relation to Human Myology: A Course of
      Lectures delivered at the Royal College of Surgeons of England.

PMID- 17232342
TI  - On Some Skulls from Ceylon.

PMID- 17232344
TI  - Some Points Concerning the Mounting of Dissections in Basins.

PMID- 17232343
TI  - Some Notes on the Manus of the Dugong.

PMID- 17232345
TI  - Archaeologia Anatomica.

PMID- 17232346
TI  - Note on a Moderator Band in the Left Ventricle and a Perforate Septum Ovale in
      the Heart of a Sheep.

PMID- 17232347
TI  - Association of American Anatomists.

PMID- 17232348
TI  - The Significance of Anatomical Variations.

PMID- 17232349
TI  - A Study of the Arrangement of the Muscular Fibres at the Upper End of the
      OEsophagus.

PMID- 17232350
TI  - The Peripheral Distribution of the Cranial Nerves of Ammocoetes.

PMID- 17232352
TI  - Eighth Report of the Committee of Collective Investigation of the Anatomical
      Society of Great Britain and Ireland, for the Year 1897-98.

PMID- 17232351
TI  - On the Origin of Vertebrates, deduced from the Study of Ammocoetes: Part III.

PMID- 17232353
TI  - Archaeologia Anatomica.

PMID- 17232354
TI  - Anatomical Notes and Queries.

PMID- 17232355
TI  - The Arrangement of the Muscular Fibres of the Stomach.

PMID- 17232356
TI  - The Marsupial Larynx.

PMID- 17232357
TI  - Congenital Malformation of the Liver-Absence of the Lobus Spigelii, Rudimentary
      Quadrate and Left Lobes, with Enlargement of the Right Lobe.

PMID- 17232358
TI  - An Interesting Case of Connection between the Lungs and Systemic Circulatory
      System and of an Abnormal Hepatic Blood Supply in a Frog (Rana temporaria).

PMID- 17232359
TI  - A Case of Uterus Masculinus-Tubular Hermaphroditism-in the Male, with Sarcomatous
      Enlargement of an Undescended Testicle.

PMID- 17232360
TI  - A New Dissection showing the Internal Gross Anatomy of the Hippocampus major.

PMID- 17232361
TI  - Note on a Foetus of Gorilla savagei.

PMID- 17232362
TI  - The Action of Certain Drugs and Mineral-Waters on the Secretion and Composition
      of Human Bile: An Experimental Investigation.

PMID- 17232363
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232364
TI  - The Convolutions of the Cerebrum of the Horse.

PMID- 17232365
TI  - On the Eyelid-Muscles of the Carchariidae and Scyllium: A Contribution to the
      Morphology of the Nictitating Membrane of Sharks.

PMID- 17232366
TI  - The Penetration of the Muscular Fibres of the Human Heart by Capillaries, and the
      Existence in that Organ of very large Capillaries.

PMID- 17232368
TI  - The Lateral Thoracic Branch of the Internal Mammary Artery.

PMID- 17232367
TI  - Observations on the Shape of the Solid Abdominal Organs.

PMID- 17232369
TI  - Example of a Large Opening between the two Auricles of the Heart, unconnected
      with the Fossa Ovalis.

PMID- 17232370
TI  - On an Atypical Case of "Strong" Current in Pfluger's Law.

PMID- 17232371
TI  - Variations in the Human Tooth-form as met with in Isolated Teeth.

PMID- 17232372
TI  - On the Condition known as ;Epignathus.'.

PMID- 17232373
TI  - On the Range of Applicability of Certain Modifications of the Weigert-Pal
      Process.

PMID- 17232374
TI  - An Osteometric Index Calculator.

PMID- 17232375
TI  - Note on the Ovarian Ova of the Hedgehog.

PMID- 17232376
TI  - Further Observations on the Anatomy of the Brain in the Monotremata.

PMID- 17232377
TI  - Archaeologia Anatomica.

PMID- 17232379
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232378
TI  - Anatomical Notes and Queries.

PMID- 17232380
TI  - The Sexual Differences of the Foetal Pelvis.

PMID- 17232381
TI  - Photographs of a Series of Sections of an Early Human Embryo.

PMID- 17232382
TI  - The Pelvic Splanchnic Nerves: An Examination into their Range and Character.

PMID- 17232383
TI  - Unilateral Renal Aplasia; "Unsymmetrical Kidney.".

PMID- 17232384
TI  - Rudimentary Clavicles and other Abnormalities of the Skeleton of a White Woman.

PMID- 17232385
TI  - On the Levator Ani, or Ischio-Anal Muscle of Ungulates, with Special Reference to
      its Morphology.

PMID- 17232387
TI  - The Sensory Distribution of the Facial Nerve in Man.

PMID- 17232386
TI  - The Morphology of the Mesenterial Development of the Vertebrate Digestive Tract.

PMID- 17232389
TI  - Anatomical Notes and Queries.

PMID- 17232388
TI  - Archaeologia Anatomica.

PMID- 17232390
TI  - Proceedings of the Association of American Anatomists.

PMID- 17232391
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232392
TI  - A System of Perivascular Lymphatic Cylinders and Capsules in the United Amnion
      Allantois of the Chick: Morphology and Use.

PMID- 17232393
TI  - The Morphological Significance of certain Fissures in the Human Liver.

PMID- 17232394
TI  - On the Topographical Anatomy of Abdominal Viscera in Man, especially the Gastro
      Intestinal Canal: Part I.

PMID- 17232395
TI  - On the Cerebellum of the Horse.

PMID- 17232396
TI  - On the Post-Embryonal History of Voluntary Muscles in Mammals.

PMID- 17232397
TI  - On a Modification of the Rutherford Microtome.

PMID- 17232398
TI  - On Proteid Digestion in Ammocoetes.

PMID- 17232400
TI  - A Radiograph of an Injected Full-Term Foetus.

PMID- 17232399
TI  - On the Origin of Vertebrates deduced from the Study of Ammocoetes: Part IV.

PMID- 17232401
TI  - A Rare Form of Palatal Suture.

PMID- 17232402
TI  - Archaeologia Anatomica.

PMID- 17232404
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232403
TI  - Anatomical Notes and Queries.

PMID- 17232405
TI  - The Palpebral and Oculomotor Apparatus in Fishes: Observations on Morphology and
      Development.

PMID- 17232406
TI  - A Comparison of the Pelvic Viscera and the Pelvic Floor in Two Adult Male
      Subjects.

PMID- 17232408
TI  - On the Medullated Fibres of some of the Cranial Nerves, and the Development of
      Certain Muscles of the Head.

PMID- 17232407
TI  - A New Osteometric Board.

PMID- 17232409
TI  - Note on the Staining of Sections while embedded in Paraffin.

PMID- 17232410
TI  - The Joints of Mammals compared with those of Man: A Course of Lectures delivered
      at the Royal College of Surgeons of England.

PMID- 17232411
TI  - An Experimental Contribution to the Study of the Mechanism of Bile Secretion.

PMID- 17232412
TI  - Note on a Group of Varieties of the Pectoral Sheet of Muscle.

PMID- 17232414
TI  - Some Experiments on Bone, with Methods of demonstrating the Canaliculi.

PMID- 17232413
TI  - On the Presence of Adrenal Structures in the Inguinal Canal.

PMID- 17232415
TI  - The Cartilages of the Monotreme Larynx.

PMID- 17232416
TI  - The Stomach and Pylorus.

PMID- 17232417
TI  - Duplicity of Cervix Uteri in Trichecus and Otaria.

PMID- 17232418
TI  - The Vitality of the Ova and Spermatozoa of Certain Animals.

PMID- 17232419
TI  - The Form of the Empty Bladder, and its Connections with the Peritoneum: Together
      with a Note on the Form of the Prostate.

PMID- 17232420
TI  - The Structure and Functions of Haemolymph Glands.

PMID- 17232421
TI  - Note on the Presence of Ciliated Cells in the Human Adult Kidney.

PMID- 17232422
TI  - Note on the Thymus Gland in the Koala (Phascolarctus cinereus).

PMID- 17232423
TI  - Symmetrical Perforations of the Parietal Bones: Including an Account of a
      Perforated and Distorted Cranium from the Liverpool Museum.

PMID- 17232424
TI  - Causes of the Entrance of Oxygen into the Blood in the Lungs.

PMID- 17232425
TI  - The Topography of the Facial Nerve in its Relation to Mastoid Operations.

PMID- 17232426
TI  - Craniometric Observations in the Post-Mortem Room.

PMID- 17232427
TI  - Ninth Report of the Committee of Collective Investigation of the Anatomical
      Society of Great Britain and Ireland, for the Year 1898-99.

PMID- 17232428
TI  - An Australian Skull with Three Supernumerary Upper Molar Teeth.

PMID- 17232429
TI  - Archaeologia Anatomica: VI.

PMID- 17232430
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232431
TI  - Separate Acromion Process.

PMID- 17232432
TI  - A Contribution to the Anatomy of the Digestive Tract in Salmo Salar.

PMID- 17232433
TI  - The Joints of Mammals compared with those of Man: A Course of Lectures delivered
      at the Royal College of Surgeons of England: Part II.

PMID- 17232434
TI  - A Modification of the Helmholtz Theory of Hearing.

PMID- 17232435
TI  - The Causes of the Shape of Non-Nucleated Red Blood Corpuscles.

PMID- 17232436
TI  - The Anterior Limit of the Cervico-Thoracic Visceral Efferent Nerves in Man.

PMID- 17232437
TI  - The Minute Structure of the Medullary Sheath of Nerve-Fibres.

PMID- 17232438
TI  - Unusual Arrangement of the Renal Portal Vein in the Frog (Rana temporaria).

PMID- 17232439
TI  - Notes on the Dissection of Two Club Feet.

PMID- 17232440
TI  - Tenth Report on Recent Teratological Literature.

PMID- 17232441
TI  - A Pericardial Sac in which the Large Azygos Vein pierced the Sac before opening
      into the Superior Vena Cava.

PMID- 17232442
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232444
TI  - Description of a Specimen in which there is a Rudimentary First Rib along with
      Thirteen Pairs of Ribs and Twenty-five Pre-Sacral Vertebrae.

PMID- 17232443
TI  - Topographical Anatomy of the Abdominal Viscera in Man, especially the Gastro
      Intestinal Canal: Part II.

PMID- 17232445
TI  - Endophlebitis.

PMID- 17232447
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232446
TI  - Origin of Vertebrates, deduced from the Study of Ammocoetes: Parts V.-VIII.

PMID- 17232448
TI  - Atresia of the Aortic Orifice, due to Anomalous Development of the Auricular
      Septum.

PMID- 17232449
TI  - Movement of the Lower End of the Radius in Pronation and Supination, and on the
      Interosseous Membrane.

PMID- 17232450
TI  - Two Anomalous Forms of Duodenal Pouches.

PMID- 17232451
TI  - The Anatomy of the Digestive Tract in the Salmon.

PMID- 17232453
TI  - Anatomical Notes and Queries.

PMID- 17232452
TI  - Archaeologia Anatomica.

PMID- 17232454
TI  - The Sternum: Its Early Development and Ossification in Man and Mammals:
      Preliminary Communication.

PMID- 17232455
TI  - Some Points in the Anatomy of the Digestive System.

PMID- 17232456
TI  - The Frequency of an Opening between the Right and Left Auricles at the Seat of
      the Foetal Foramen Ovale.

PMID- 17232457
TI  - Absence of the Inferior Cava Below the Diaphragm.

PMID- 17232458
TI  - Note on the Configuration of the Heart in Man and some other Mammalian Groups.

PMID- 17232459
TI  - The True Caecal Apex, or the Vermiform Appendix: Its Minute and Comparative
      Anatomy.

PMID- 17232460
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232462
TI  - On the Destruction of Leucocytes.

PMID- 17232461
TI  - On the Arrangement of the Fasciae of the Pelvis and their Relationship to the
      Levator Ani.

PMID- 17232463
TI  - A Differential Stain for Muscular and Fibrous Tissues.

PMID- 17232464
TI  - Degenerations resulting from Lesions of the Cortex of the Temporal Lobe.

PMID- 17232465
TI  - Topographical Anatomy of the Abdominal Viscera in Man, especially the Gastro
      Intestinal Canal: Part III.

PMID- 17232466
TI  - Stop or Click Mechanism in the Animal Kingdom.

PMID- 17232467
TI  - Observations on the Structure of the Third, Fourth, and Sixth Cranial Nerves.

PMID- 17232468
TI  - On the Origin of Vertebrates, deduced from the Study of Ammocoetes.

PMID- 17232469
TI  - Aberdeen University Anatomical and Anthropological Society.

PMID- 17232471
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232470
TI  - Archaeologia Anatomica.

PMID- 17232472
TI  - Topographical Anatomy of the Abdominal Viscera in Man, especially the Gastro
      Intestinal Canal: Part IV.

PMID- 17232473
TI  - Hair-Slope in Man.

PMID- 17232474
TI  - Abnormal Veins in the Frog.

PMID- 17232475
TI  - Morphology of the Human Urinogenital Tract.

PMID- 17232476
TI  - Pathology of the Bladder and Ureter-Extroversio Vesicae and Apparent Low
      Implantation of the Ureter End.

PMID- 17232477
TI  - Osteology of the Penguins.

PMID- 17232478
TI  - Osteology of Scopus ambretta and Baloeniceps rex.

PMID- 17232479
TI  - Joint in Fowl's Tongue and its Vocal Function.

PMID- 17232481
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232480
TI  - Notches and Fissures of the Spleen.

PMID- 17232482
TI  - Natural Subdivision of the Cerebral Hemisphere.

PMID- 17232483
TI  - On Professor Pearson's Contributions to Osteology.

PMID- 17232484
TI  - Effect of Thyroidectomy upon Nitrogenous Metabolism.

PMID- 17232485
TI  - Case of Hereditary Brachydactly.

PMID- 17232487
TI  - Anomalous Structure at and about Base of Bladder.

PMID- 17232486
TI  - The Superior Tibio-Fibular Joint.

PMID- 17232488
TI  - Anomaly of Omo-Hyoid.

PMID- 17232489
TI  - Double Left Parietal Bone in a Scottish Skull.

PMID- 17232491
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232490
TI  - Eleventh Report on Recent Teratological Literature.

PMID- 17232492
TI  - A Contribution to the Study of the Morphology of Adipose Tissue.

PMID- 17232493
TI  - Structure of the Left Auriculo-Ventricular Valve in Birds.

PMID- 17232494
TI  - The Development of the Renal-Portals and Fate of the Posterior Cardinal Veins in
      the Frog.

PMID- 17232495
TI  - "Socia Thymi Cervicalis," and Thymus Accessorius.

PMID- 17232496
TI  - A Case of Rudimentary First Thoracic Rib in a Horse.

PMID- 17232497
TI  - A Case of Congenital Malformation of the Heart, with Abnormalities of Abdominal
      Viscera: Absence of Spleen, Absence of Hepatic Section of Inferior Cava.

PMID- 17232498
TI  - Two Cases of Supernumerary Radio-Palmar Muscle-Muscle Surnumeraire Radio-Palmaire
      of Testut.

PMID- 17232499
TI  - Case of Multiple Renal Arteries.

PMID- 17232500
TI  - Description of a Foetus Amorphus.

PMID- 17232501
TI  - Acardiac Monster caused by a Foetal Adhesion to a Placenta Succenturiata.

PMID- 17232502
TI  - Aberdeen University Anatomical and Anthropological Society.

PMID- 17232504
TI  - The Form and Form-Relations of the Human Cerebral Ventricular Cavity.

PMID- 17232503
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232505
TI  - The Peritoneum of the Pelvic Cavity.

PMID- 17232506
TI  - Salmo Salar. The Digestive Tract in Kelts.

PMID- 17232508
TI  - Hyoid Apparatus in Man, in which a Separate Epi-hyal Bone was developed.

PMID- 17232507
TI  - Some Observations on the Origin and Nature of the so-called Hydatids of Morgagni
      found in Men and Women, with Especial Reference to the Fate of the Mullerian Duct
      in the Epididymis.

PMID- 17232509
TI  - The Origin of Vertebrates, deduced from the Study of Ammocoetes: Part X.

PMID- 17232511
TI  - On the Development of the Head Muscles in the Newt.

PMID- 17232510
TI  - The Relation of Structure and Function as illustrated by the Form of the Lower
      Epiphysial Suture of the Femur.

PMID- 17232512
TI  - The Separate Functions of Different Parts of the Rima Glottidis.

PMID- 17232514
TI  - Note on Irregularities in the Conformation of the Post-Orbital Wall in Skulls of
      Hylobates Mulleri, and of an Aboriginal Native of Australia.

PMID- 17232513
TI  - On an Unusual Form of Nasal Bone in a Human Skull.

PMID- 17232515
TI  - An Ischiopagus Tripus (Human), with Special Reference to the Anatomy of the
      Composite Limb.

PMID- 17232516
TI  - Rare Anomaly of the Aortic Arch.

PMID- 17232517
TI  - Anomalies in the Cervical and Upper Thoracic Region, involving the Cervical
      Vertebrae, First Rib, and Brachial Plexus.

PMID- 17232518
TI  - Contribution to our Knowledge of the Chemistry of Red Bone Marrow.

PMID- 17232519
TI  - Twelfth Report on Recent Teratological Literature.

PMID- 17232520
TI  - Homologies of the Cerebral Sulci.

PMID- 17232521
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232522
TI  - On the Succession and Homologies of the Molar and Premolar Teeth in the Mammalia.

PMID- 17232523
TI  - The Normal Position of the Big Toe.

PMID- 17232524
TI  - Two Cases of Dental Anomaly.

PMID- 17232525
TI  - A Note on the Occipito-Atloid Articulation in some Arctoids.

PMID- 17232526
TI  - Two Rare Vertebral Anomalies.

PMID- 17232527
TI  - On the Natural Preservation of the Brain in the Ancient Egyptians.

PMID- 17232528
TI  - The Primary Subdivision of the Mammalian Cerebellum.

PMID- 17232529
TI  - On the Presence of an Additional Incisor Tooth in a Prehistoric Egyptian.

PMID- 17232531
TI  - On the Arrangement of the Branches of the Mammalian Aortic Arch.

PMID- 17232530
TI  - Note on a Case of Muscular Abnormality observed during life.

PMID- 17232532
TI  - The Relative Weights of the Right and Left Sides of the Body in the Foetus.

PMID- 17232533
TI  - The Comparative Histology of the Urethra.

PMID- 17232535
TI  - Emargination of the Patella.

PMID- 17232534
TI  - A Supraclavicularis Proprius (Gruber).

PMID- 17232537
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232536
TI  - Aberdeen University Anatomical Anthropological Society.

PMID- 17232538
TI  - The Early Stages of the Development of the Pericardium.

PMID- 17232539
TI  - The Extent to which the Posterior Segments of the Body have been Transmuted and
      Suppressed in the Evolution of Man and Allied Primates.

PMID- 17232541
TI  - A Study of the Cerebral Cortex in a Case of Congenital Absence of the Left Upper
      Limb.

PMID- 17232540
TI  - Some Cardiographic Tracings from the Base of the Human Heart.

PMID- 17232542
TI  - The Form of the Human Spleen.

PMID- 17232543
TI  - Preliminary Note on the Position of the Gall-Bladder in the Human Subject.

PMID- 17232544
TI  - The Development of the Head Muscles in Scyllium Canicula.

PMID- 17232545
TI  - The Skeleton of a Native Australian.

PMID- 17232547
TI  - On the Development of the Pterygo-quadrate Arch in the Lacertilia.

PMID- 17232546
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232548
TI  - On the Development and Homology of the Mammalian Cerebellar Fissures: Part I.

PMID- 17232549
TI  - The Evolution of the Teeth in the Mammalia.

PMID- 17232550
TI  - The Form of the Dilated Cerebral Ventricles in Chronic Brain Atrophy.

PMID- 17232551
TI  - On the Origin of Vertebrates Deduced from the Study of Ammocoetes.

PMID- 17232552
TI  - Are the Cranial Contents Displaced and the Brain Damaged by Freezing the Entire
      Head?

PMID- 17232554
TI  - Development and Homology of the Mammalian Cerebellar Fissures: Part II.

PMID- 17232553
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232555
TI  - Observations on the Relations of the Deeper Parts of the Brain to the Surface.

PMID- 17232556
TI  - An Example of a Peculiar Malformation of the Tricuspid Valve of the Heart.

PMID- 17232557
TI  - Note on a Second Example of Division of the Cavity of the Left Auricle into Two
      Compartments by a Fibrous Band.

PMID- 17232558
TI  - The Cerebrum of a Microcephalic Idiot.

PMID- 17232559
TI  - Some Anomalies in Nerves arising from the Lumbar Plexus, and a Bilaminar Musculus
      Pectineus in a Foetus; and on Variations in Nerve Supply in Man and some other
      Mammals.

PMID- 17232560
TI  - Complete Absence of the Superficial Flexors of the Thumb and concurrent Muscular
      Anomalies.

PMID- 17232561
TI  - A Method of Obtaining Uniplanar Sections with the Ordinary Rocking Microtome.

PMID- 17232562
TI  - Archaeologia Anatomica.

PMID- 17232564
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232563
TI  - Thirteenth Report on Recent Teratological Literature.

PMID- 17232565
TI  - The Meaning of some of the Epiphyses of the Pelvis.

PMID- 17232566
TI  - The so-called ;Gyrus Hippocampi.'.

PMID- 17232567
TI  - Notes on the Morphology of the Cerebellum.

PMID- 17232568
TI  - Preliminary Communication on some Cephalometric Data bearing upon the Relation of
      the Size and Shape of the Head to Mental Ability.

PMID- 17232569
TI  - Form-Relations of the Dilated Cerebral Ventricles in Chronic Brain Atrophy.

PMID- 17232570
TI  - Abnormalities in Sacral and Lumbar Vertebrae of Skeletons of Australian
      Aborigines.

PMID- 17232571
TI  - Rudimentary Condition of Carotid Canal.

PMID- 17232572
TI  - Some Peculiar Features in a Temporal Bone.

PMID- 17232574
TI  - Occurrence of a ;Principal Islet' in the Pancreas of Teleostei: Preliminary Note.

PMID- 17232573
TI  - Case of Feather-Bifurcation.

PMID- 17232575
TI  - Method of Preparing the Membranous Labyrinth.

PMID- 17232576
TI  - Two Hearts showing Peculiarities of the Great Veins.

PMID- 17232577
TI  - General Characters of Crania of People of Scotland.

PMID- 17232578
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232580
TI  - Case of Abnormal Arrangement of Aortic Valves.

PMID- 17232579
TI  - Abnormalities of the Renal Arteries, with Remarks on their Development and
      Morphology.

PMID- 17232581
TI  - Chemical Study of the Hibernating Gland of the Hedgehog, together with the
      Changes which it undergoes during Winter Sleep.

PMID- 17232583
TI  - Discussion of some Points in connection with the Suprarenal Glands-Cortical and
      Medullary.

PMID- 17232582
TI  - Note on an Abnormal Colon.

PMID- 17232584
TI  - Abnormal Nasal Bones.

PMID- 17232585
TI  - The Lower Cervical Fasciae.

PMID- 17232587
TI  - The Influence of the Patella in Extension of the Knee-Joint.

PMID- 17232586
TI  - Case of Accessory Patellae in the Human Subject, with Remarks on Emargination of
      the Patella.

PMID- 17232588
TI  - The ;Unsymmetrical' Kidney:-Its Compensatory Enlargement.

PMID- 17232590
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232589
TI  - The Germ-Cells.

PMID- 17232591
TI  - A Comparative Study of the Grey and White Matter, of the Motor-Cell Groups, and
      of the Spinal Accessory Nerve, in the Spinal Cord of the Porpoise (Phocoena
      Communis).

PMID- 17232592
TI  - Skulls from the Round Barrows of East Yorkshire.

PMID- 17232593
TI  - The Varieties of the Os Calcis.

PMID- 17232594
TI  - Further Observations on the Functions of the Spleen and other Haemolymph Glands.

PMID- 17232595
TI  - Note on an Exceptional Human Brain, presenting a Pithecoid Abnormality of the
      Sylvian Region.

PMID- 17232596
TI  - Note on the Communication between the Musculo-Spiral and Ulnar Nerves.

PMID- 17232597
TI  - The Fossa Parieto-Occipitalis.

PMID- 17232598
TI  - The Insertion of the Pyriformis and Obturator Internus, and Formation of the
      Posterior Circular Capsular Fibres and Upper Retinaculum of Weitbrecht.

PMID- 17232599
TI  - Lectures on the Early Stages in the Development of Mammalian Ova and on the
      Formation of the Placenta in Different Groups of Mammals: Lecture I.

PMID- 17232600
TI  - The Germ-Cells: Part I.

PMID- 17232602
TI  - A Study of the Astragalus.

PMID- 17232601
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232603
TI  - Observations on Traction Epiphyses.

PMID- 17232605
TI  - On the Presence and Significance of the Superior Commissure throughout the
      Vertebrata.

PMID- 17232604
TI  - John Gratton's Craniometer and Craniometric Methods.

PMID- 17232606
TI  - A Method of Demonstrating Tracings to Large Audiences.

PMID- 17232607
TI  - A Comparative Study of the Grey and White Matter, of the Motor-Cell Groups, and
      of the Spinal Accessory Nerve, in the Spinal Cord of the Porpoise (Phocoena
      Communis): Part II.

PMID- 17232608
TI  - Observations upon the Distribution and Structure of Haemolymph Glands in Mammalia
      and Aves, including a Preliminary Note on the Thymus.

PMID- 17232609
TI  - Lectures on the Early Stages in the Development of Mammalian Ova and on the
      Differentiation of the Placenta in Different Groups of Mammals: Lecture II.

PMID- 17232610
TI  - The Germ-Cells: Part I.

PMID- 17232611
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232612
TI  - On Certain Markings, due to Nerves and Blood-Vessels, upon the Cranial Vault;
      their Significance and the Relative Frequency of their Occurrence in the
      Different Races of Mankind.

PMID- 17232613
TI  - The True Form of the Brachial Plexus, and its Motor Distribution.

PMID- 17232614
TI  - A Study of the Astragalus.

PMID- 17232615
TI  - Some Observations on the Level at which the Lower Border of the Third Part of the
      Duodenum crosses the Vertebral Column.

PMID- 17232616
TI  - The Anatomy of the Visceral Pelvic Fascia.

PMID- 17232617
TI  - The Mammalian Cerebellum: Its Lobes and Fissures.

PMID- 17232618
TI  - Multiple Malformations (Genito-Urinary and Skeletal) occurring on One Side of the
      Body in a Case of Atresia Ani.

PMID- 17232620
TI  - Professor Wilhelm His.

PMID- 17232619
TI  - Lectures on the Early Stages in the Development of Mammalian Ova, and on the
      Differentiation of the Placenta in Different Groups of Mammals: Lecture III.

PMID- 17232621
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232622
TI  - The Derivation and Significance of certain Supernumerary Muscles of the Pectoral
      Region.

PMID- 17232623
TI  - The Histology of Lymphatic Glands: The General Structure, the Reticulum, and the
      Germ Centres.

PMID- 17232624
TI  - A Heart presenting a Septum across the Left Auricle.

PMID- 17232625
TI  - A Study of the Astragalus.

PMID- 17232626
TI  - An OEsophageal Pouch with Absence of Signs of any Pathological Cause.

PMID- 17232627
TI  - Morphology of the Human Intertransverse Muscles.

PMID- 17232628
TI  - The Mammalian Cerebellum: Its Lobes and Fissures.

PMID- 17232629
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232630
TI  - Two Cases of Fourth Molar Teeth in the Skulls of an Australian Aboriginal and a
      New Caledonian.

PMID- 17232631
TI  - The Development of the Retina in Amphibia: an Embryological and Cytological
      Study: Part I.

PMID- 17232632
TI  - The Relations of the Superior Oblique Muscle of the Eye in the Mammals.

PMID- 17232633
TI  - The Os Calcis: Part II.

PMID- 17232634
TI  - The Histology of Lymphatic Glands: the General Structure, the Reticulum, and the
      Germ Centres: Part II.

PMID- 17232635
TI  - On the Presence of a Supernumerary Milk Incisor in the Human Dentition.

PMID- 17232636
TI  - The Theory of Nerve Components, especially with regard to its Relation to the
      Segmentation of the Vertebrate Head.

PMID- 17232637
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232638
TI  - The Nature of the Mammalian Diaphragm and Pleural Cavities.

PMID- 17232639
TI  - Dissociation in Certain Vital Phenomena.

PMID- 17232640
TI  - Observations on the Lumbar Arteries.

PMID- 17232641
TI  - The Small or Superficial Thyro-Arytenoideus Muscle.

PMID- 17232643
TI  - The Development of the Retina in Amphibia: an Embryological and Cytological
      Study: Part II.

PMID- 17232642
TI  - The Myology of the Hind Limb of the Marsupial Mole (Notoryctes typhlops).

PMID- 17232644
TI  - Anatomical Notes upon the Membranous Labyrinth of Man and of the Seal.

PMID- 17232645
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232646
TI  - On the Origin of Vertebrates deduced from the Study of Ammocoetes: Part XII.

PMID- 17232647
TI  - On Pressure Epiphyses.

PMID- 17232648
TI  - On Imbrication of the Papillary Ridges in Man.

PMID- 17232649
TI  - Skulls from the Round Barrows of East Yorkshire.

PMID- 17232650
TI  - The Anatomy of a Sirenomelian Monster.

PMID- 17232651
TI  - Cranio-cerebral Topography.

PMID- 17232653
TI  - A Note on the Variations of the Tibia and Astragalus.

PMID- 17232652
TI  - The Development of the Retina in Amphibia: an Embryological and Cytological
      Study: Part III.

PMID- 17232654
TI  - On the Limits of the Sensibility to Odours and of the Methods of detecting
      Emanations.

PMID- 17232655
TI  - A Curious Abnormality of the Renal Arteries.

PMID- 17232656
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232657
TI  - On the Development of the Hind-Brain of the Pig: Part I.

PMID- 17232658
TI  - Note on the Elastic Tissue in the Eye of Birds: Part I.

PMID- 17232659
TI  - Pigmentation of the Pia Mater, with Special Reference to the Brain of Modern
      Egyptians.

PMID- 17232660
TI  - A Case of Congenital Atresia of Pulmonary Artery, with Transposition of Viscera.

PMID- 17232661
TI  - On the Homology and Morphology of the Popliteus Muscle: A Contribution to
      Comparative Myology.

PMID- 17232662
TI  - The Facial Expression of Violent Effort, Breathlessness, and Fatigue.

PMID- 17232663
TI  - A Case of Absence of the Corpus Callosum.

PMID- 17232665
TI  - An Acardiac Foetus.

PMID- 17232664
TI  - The Circle of Willis: an Examination of 700 Specimens.

PMID- 17232666
TI  - The Presence of a Vestigial Sixth Branchial Arch in the Heterodontidae.

PMID- 17232667
TI  - PREFACE TO THE FORTIETH VOLUME.

PMID- 17232668
TI  - Observations on the Cetacean Flipper, with Special Reference to Hyperphalangism
      and Polydactylism.

PMID- 17232669
TI  - Note on the Elastic Tissue in the Eye of Birds: Part II.

PMID- 17232670
TI  - Pulmonary Changes in Asphyxia.

PMID- 17232671
TI  - On the Development of the Hind-Brain of the Pig: Part II.

PMID- 17232672
TI  - A Study of the Astragalus: Part IV.

PMID- 17232673
TI  - The Arrangement of the Elastic Fibres in the Bronchi and Lung.

PMID- 17232674
TI  - A New Method of Demonstrating the Topographical Anatomy of the Adult Human Skull.

PMID- 17232675
TI  - A Note upon the Mode of Termination of the Posterior Tibial Artery and Nerve.

PMID- 17232676
TI  - On the Fate of the "Taenia Clino-Orbitalis" (Gaupp) in Echidna and in
      Ornithorhynchus respectively; with Demonstration of Specimens and Stereo
      Photographs.

PMID- 17232678
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232677
TI  - Note on the Development of the Thymus Gland in Lepidosiren paradoxa.

PMID- 17232679
TI  - On the Surgical Anatomy of the Prostate.

PMID- 17232680
TI  - On the Anatomy of the Calamus Region in the Human Bulb; with an Account of a
      hitherto undescribed "Nucleus postremus.": Part I.

PMID- 17232681
TI  - Notes on the Coronal Suture.

PMID- 17232682
TI  - A Note on the Topographical Anatomy of the Caput Gyri Hippocampi.

PMID- 17232684
TI  - Experimental Contribution to a Theory of Thinking.

PMID- 17232683
TI  - The Vermiform Appendix of Man, and the Structural Changes therein coincident with
      Age.

PMID- 17232685
TI  - On Some Minor Markings on Bones.

PMID- 17232686
TI  - On the Presence of Elastic Fibres in the Cornea.

PMID- 17232687
TI  - An Unusual Displacement of the Heart.

PMID- 17232688
TI  - On the Origin of Vertebrates, deduced from the Study of Ammocoetes.

PMID- 17232689
TI  - The Cerebellum of Petromyzon fluviatilis.

PMID- 17232690
TI  - Remarks on the Innervation of the Dorsum Manus, with Special Reference to Certain
      Rare Abnormalities.

PMID- 17232691
TI  - A Case of Ectopia viscerum, associated with Spina bifida and other Abnormalities.

PMID- 17232692
TI  - On the Anatomy on the Calamus Region in the Human Bulb; with an Account of a
      hitherto undescribed "Nucleus postremus.": Part II.

PMID- 17232694
TI  - Notes on (a) The Origin of Elastic Fibres in Tendon; (b) Branching of Young
      Tendon Cells.

PMID- 17232693
TI  - Supernumerary Limb in a Frog.

PMID- 17232695
TI  - On the Development, Ossification, and Growth of the Palate Bone of Man.

PMID- 17232696
TI  - An Abnormal Vermiform Appendix in the Rabbit.

PMID- 17232697
TI  - On a Specimen of the Hind-gut opening into a Cloacal Chamber in a Child.

PMID- 17232698
TI  - A Record of the Decussations of the Brachial Plexus in Man.

PMID- 17232699
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232700
TI  - Note on an Unusual Anomaly in Crania from the Island of Kwaiawata, New Guinea.

PMID- 17232701
TI  - Notes on the Anatomy of an Eunuchoid Man dissected at the Anatomy School,
      Cambridge, during 1905.

PMID- 17232702
TI  - The Papillary Ridges and Papillary Layer of the Corium in the Mammalian Hand and
      Foot.

PMID- 17232703
TI  - Anatomical Notes.

PMID- 17232704
TI  - Hour-Glass Stomach.

PMID- 17232705
TI  - A Rare Anomaly of the Carotid Arteries (Internal and External).

PMID- 17232706
TI  - Three Cases of Malformation of the Tracheo-OEsophageal Septum.

PMID- 17232707
TI  - Two Cases of Fusion of the Semilunar and Cuneiform Bones in Negroes.

PMID- 17232709
TI  - Partial Deficiency of the Pericardium.

PMID- 17232708
TI  - Epilunar and Hypolunar Ossicles, Division of the Scaphoid, and other
      Abnormalities in the Carpal Region.

PMID- 17232710
TI  - The Development and Evolution of the "Papillary" Ridges and Patterns on the Volar
      Surface of the Hand.

PMID- 17232711
TI  - The Anatomical Variations presented by a Case of a Thoracopagous Lamb Monster,
      together with an Account of the Developmental Explanation of the same.

PMID- 17232712
TI  - The Histogenesis of Nerve Fibres: A Cytological Study of the Embryonic Cell
      Nucleus.

PMID- 17232713
TI  - Observations on the Head of the Tibia.

PMID- 17232714
TI  - Note on a Case of Abnormal Disposition of the Peritoneum.

PMID- 17232715
TI  - Varying Positions of the Carpal Bones in the Different Movements at the Wrist:
      Part I.

PMID- 17232716
TI  - Notes on Predynastic Egyptian Tibiae.

PMID- 17232717
TI  - A Description of the Peritoneal Cavity, founded on Clinical and Pathological
      Investigations.

PMID- 17232718
TI  - The Interpretation of the Primary and First Secondary Wave in Sphygmograph
      Tracings.

PMID- 17232719
TI  - Note on Accessory Coronary Arteries.

PMID- 17232720
TI  - Complete Bilateral Interruption of the Fissure of Rolando.

PMID- 17232721
TI  - Congenital Obliteration of a Portion of the Alimentary Canal.

PMID- 17232722
TI  - The Physiology of the Lateral Atlanto-Axial Joints.

PMID- 17232723
TI  - The Arrangement of the Synovial Membrane in the Palmar Digital Sheaths.

PMID- 17232724
TI  - The Mechanical Supports of the Pelvic Viscera.

PMID- 17232725
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232726
TI  - Description of a Human Embryo of Twenty-Three Paired Somites.

PMID- 17232727
TI  - The Form and Nature of the Muscular Connections between the Primary Divisions of
      the Vertebrate Heart.

PMID- 17232728
TI  - Rare Anomaly of the Human Heart-A Three-Chambered Heart in an Adult aged Thirty
      Five Years.

PMID- 17232729
TI  - New Studies on the Folding of the Visual Cortex and the Significance of the
      Occipital Sulci in the Human Brain.

PMID- 17232730
TI  - Report on a Cranium with Greatly Reduced and Irregular Dentition.

PMID- 17232731
TI  - Description of a Human Cranium from Walfisch Bay, S.W. Africa.

PMID- 17232732
TI  - Some Rare Abnormalities in Teeth.

PMID- 17232733
TI  - Notes on a Prehistoric Skeleton found in a Cave in Littondale, Yorkshire.

PMID- 17232735
TI  - The Causation of the Symmetrical Thinning of the Parietal Bones in Ancient
      Egyptians.

PMID- 17232734
TI  - Abnormalities of the Pyramidal Tracts.

PMID- 17232736
TI  - On Certain Peculiarities of Brains lacking a Corpus Callosum.

PMID- 17232737
TI  - Asymmetry of the Brain and Skull.

PMID- 17232738
TI  - A New Topographical Survey of the Human Cerebral Cortex, being an Account of the
      Distribution of the Anatomically Distinct Cortical Areas and their Relationship
      to the Cerebral Sulci.

PMID- 17232739
TI  - A Study of the Navicular in the Human and Anthropoid Foot.

PMID- 17232740
TI  - Varying Positions of the Carpal Bones in the Different Movements at the Wrist:
      Part II.

PMID- 17232741
TI  - A Brain with Complete Absence of the Corpus Callosum.

PMID- 17232742
TI  - A Case of Fusion of the Semilunar and Cuneiform Bones.

PMID- 17232743
TI  - A Method for Determining the Position of the Base of the Eye-Socket.

PMID- 17232745
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232744
TI  - The Lateral Fixation of the Cervix Uteri.

PMID- 17232746
TI  - An Account of the Structures concerned in the Production of the Jugular Pulse.

PMID- 17232748
TI  - The Fascia of the Pelvis.

PMID- 17232747
TI  - Pelvic Muscles and Fasciae.

PMID- 17232749
TI  - The Evolution of Man's Teeth, founded upon a Study of the Development of the
      Teeth of the Australian Aboriginal.

PMID- 17232751
TI  - A Method of indicating the Position of the Diaphragm and estimating the Degree of
      Visceroptosis.

PMID- 17232750
TI  - Seventeenth Report on Recent Teratological Literature.

PMID- 17232752
TI  - On the Form of the Caecum.

PMID- 17232753
TI  - The Microscopical Anatomy of the Genital Tract in the Rat Kangaroo (Female).

PMID- 17232754
TI  - On the Role of the Developing Epidermis in forming Sheaths and Lumina to Organs,
      illustrated specially in the Development of the Prepuce and Urethra.

PMID- 17232755
TI  - The Presence of a False Acetabulum in a Species of Bandicoot.

PMID- 17232756
TI  - The Relationship between the Internal Structure of the Upper Part of the Femur
      and Fractures through the Base of the Neck of the Femur.

PMID- 17232757
TI  - On the Brains of Aboriginal Natives of Australia in the Anatomy School, Cambridge
      University: Part I.

PMID- 17232758
TI  - Anomalies in the Supra-inial Portion of the Occipital Bone, resulting from
      Irregularities of its Ossification, with Consequent Variations of the
      Interparietal Bone.

PMID- 17232759
TI  - A Note on the Crura of the Diaphragm and the Muscle of Treitz.

PMID- 17232760
TI  - On the Real Nature of the so-called "Pelvic Fascia.".

PMID- 17232761
TI  - The Comparative Anatomy, Gross and Minute, of the Thyroid and Parathyroid Glands
      in Mammals and Birds: Part I.

PMID- 17232762
TI  - A Note on the Development of the Septum Transversum and the Liver.

PMID- 17232763
TI  - The Brains of Aboriginal Natives of Australia in the Anatomy School, Cambridge
      University: Part II.

PMID- 17232764
TI  - Studies in the Anatomy of the Pelvis, with Special Reference to the Fasciae and
      Visceral Supports: Part I.

PMID- 17232765
TI  - An Unusual Duodenal Diverticulum.

PMID- 17232766
TI  - A Case of Accessory Lobe of the Right Lung.

PMID- 17232767
TI  - Further Observations on the Development of the Teeth of the Australian
      Aboriginal.

PMID- 17232768
TI  - Note on a Tendon found in Association with the Insertion of the Peroneus Longus,
      and Origin of the First Dorsal Interosseous Muscles.

PMID- 17232769
TI  - Description of a Human Embryo of 13-14 Mesodermic Somites.

PMID- 17232770
TI  - Studies in the Anatomy of the Pelvis, with Special Reference to the Fasciae and
      Visceral Supports: Part II.

PMID- 17232771
TI  - The Brains of Aboriginal Natives of Australia in the Anatomy School, Cambridge
      University: Part III.

PMID- 17232772
TI  - Development of the Spleen.

PMID- 17232773
TI  - The Comparative Anatomy, Gross and Minute, of the Thyroid and Parathyroid Glands
      in Mammals and Birds: Part II.

PMID- 17232774
TI  - Imperfect Torsion of the Intestinal Loop.

PMID- 17232775
TI  - The Derivation of the Human Hypothenar Muscles.

PMID- 17232776
TI  - The Cameragraph: A Drawing Apparatus.

PMID- 17232777
TI  - Two Cases of Hermaphroditism.

PMID- 17232778
TI  - A Case of Fusion of the Semilunar and Cuneiform Bones (Os lunato-triquetrum) in
      an Australian Aboriginal.

PMID- 17232779
TI  - Anatomical Notes.

PMID- 17232780
TI  - Descriptions of Three Chinese Brains presented by Dr F. W. Mott, F.R.S., to the
      Museum of the Royal College of Surgeons: Part I.

PMID- 17232781
TI  - Tooth-Vestiges and Associated Mouth Parts in the Manidae.

PMID- 17232782
TI  - Further Remarks on Traction Epiphyses.

PMID- 17232784
TI  - Synovial Membranes, with Special Reference to those related to the Tendons of the
      Foot and Ankle.

PMID- 17232783
TI  - A Study of the Cuboid and Os Peroneum in the Primate Foot.

PMID- 17232785
TI  - Multiple Anomalies in the Upper Extremities of One Cadaver.

PMID- 17232787
TI  - Anatomical Notes.

PMID- 17232786
TI  - The Fascia of the Perineum and Pelvis of the Female, with Special Reference to
      the Mechanical Supports of the Pelvic Viscera.

PMID- 17232788
TI  - A Contribution to the Morphology and Development of the Mammalian Liver.

PMID- 17232789
TI  - Eighteenth Report on Recent Teratological Literature (1907).

PMID- 17232790
TI  - The Interscapular Gland.

PMID- 17232791
TI  - Descriptions of Three Chinese Brains presented by Dr F. W. Mott, F.R.S., to the
      Museum of the Royal College of Surgeons: Part II.

PMID- 17232792
TI  - The Cutaneous Branches of the Posterior Primary Divisions of the Spinal Nerves,
      and their Distribution in the Skin.

PMID- 17232793
TI  - An Inquiry into the Physiological Mechanism of Respiration, with Especial
      Reference to the Movements of the Vertebral Column and Diaphragm.

PMID- 17232794
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232795
TI  - The Form of the Rectum.

PMID- 17232797
TI  - The Variability of the Last Lumbar Vertebra.

PMID- 17232796
TI  - Description of a Model of the Brain of a Foetal Cat 20 mm. in Length.

PMID- 17232798
TI  - Descriptions of Three Chinese Brains presented by Dr F. W. Mott, F.R.S., to the
      Museum of the Royal College of Surgeons: Part III.

PMID- 17232799
TI  - The Mechanical and Physiological Effects of an Excessive Dilatation and
      Elongation of the Colon.

PMID- 17232800
TI  - Anatomical Notes.

PMID- 17232801
TI  - The Development of the Male Urethra, and a Case of Imperforate Urethra in a
      Foetus, fully described.

PMID- 17232803
TI  - External Features of an Early Human Embryo with a Distended Amnion.

PMID- 17232802
TI  - The Means of Displaying, by Ordinary Dissection, the Larger Tracts of White
      Matter of the Brain in their Continuity.

PMID- 17232804
TI  - On a Case of Displacement of the Descending Colon.

PMID- 17232805
TI  - The Nature and Cause of the Physiological Descent of the Testes.

PMID- 17232807
TI  - A Rare Condition of Wormian Ossifications.

PMID- 17232806
TI  - Note on the Innominate Bone as a Factor in the Determination of Sex: with Special
      Reference to the Sulcus Praeauricularis.

PMID- 17232808
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232809
TI  - The Topography and Morphology of the Human Hyoid Bone.

PMID- 17232810
TI  - The Arrangement of Papillary Ridges on the Human Hand and Foot.

PMID- 17232811
TI  - Abnormal Position of the Heart and Great Blood-Vessels associated with
      Transposition of the Viscera.

PMID- 17232812
TI  - A Note on a Large Intra-Abdominal Pelvic Colon and on the AEtiology of Peritoneal
      Adhesions.

PMID- 17232813
TI  - Note on an Anomalous Anastomosis between the Internal Carotid and Basilar
      Arteries.

PMID- 17232814
TI  - A Gland upon the Ear Conch of Dasyurus Maugei.

PMID- 17232816
TI  - Two Abnormal Sterna in Living Subjects.

PMID- 17232815
TI  - A Contribution to the Development of the Prostate in Man.

PMID- 17232817
TI  - A Case of Abnormal Right Subclavian Artery.

PMID- 17232819
TI  - A Liver exhibiting Multiple Anomalies.

PMID- 17232818
TI  - A Contribution to the Histology of the Human Osseous and Membranous Labyrinth.

PMID- 17232820
TI  - Anatomical Notes.

PMID- 17232821
TI  - Anatomical Notes.

PMID- 17232822
TI  - The Physiological Descent of the Ovaries in the Human Foetus.

PMID- 17232823
TI  - The Anatomy of the Palatine Tonsils.

PMID- 17232824
TI  - The Nature and Cause of the Physiological Descent of the Testes.

PMID- 17232825
TI  - Obliteration of the Left Common, External, and Internal Iliac Arteries.

PMID- 17232827
TI  - Abnormal Phalanges in a Human Hand: A Case of Brachydactyly.

PMID- 17232826
TI  - A Cyclopean Foetus with Hernia Encephali.

PMID- 17232828
TI  - Congenital Deficiency of a Portion of the Thoracic Skeleton.

PMID- 17232829
TI  - A Case of Os Parietale Bipartitum in an Australian Aboriginal Skull.

PMID- 17232830
TI  - Further Observations on the Ossification of the Human Lower Jaw.

PMID- 17232831
TI  - Nineteenth Report on Recent Teratological Literature (1908).

PMID- 17232832
TI  - Proceedings of the Anatomical Society of Great Britain and Ireland.

PMID- 17232833
TI  - The Development of the Auditory Nerve in Vertebrates.

PMID- 17232834
TI  - The Arrangement of the Bursae in the Superior Extremities of the Full-time
      Foetus.

PMID- 17232835
TI  - The Morphology of the Testis.

PMID- 17232836
TI  - Note on the Influence of Posture on the Facets of the Patella.

PMID- 17232837
TI  - Abnormal Ossification of Meckel's Cartilage.

PMID- 17232838
TI  - On the Carotid Sheath and other Fascial Planes.

PMID- 17232839
TI  - The Development of the Larynx.

PMID- 17232841
TI  - Anatomical Notes.

PMID- 17232840
TI  - The Embedding of the Embryo Guinea-Pig in the Uterine Wall and its Nutrition at
      that Stage of Development.

PMID- 17232842
TI  - Notes on the Development of the Human Sphenoid.

PMID- 17232843
TI  - The Architecture of the Cancellous Tissue forming the Upper End of the Femur.

PMID- 17232844
TI  - The Pituitary Fossa and Certain Skull Measurements.

PMID- 17232845
TI  - The Arrangement of the Fibres of the Middle Cerebellar Peduncle, as shown by
      Dissection.

PMID- 17232846
TI  - Case of an Abnormal Sinuous Aorta.

PMID- 17232847
TI  - Two Cases of Reduplication of the Arteria Cerebri Posterior.

PMID- 17232848
TI  - The Presence of Lachrymo-Jugal Sutures in Two Human Skulls.

PMID- 17232849
TI  - Description of a New Craniometer and of Certain Age Changes in the Anthropoid
      Skull.

PMID- 17232850
TI  - The Limb Arteries of Primates: Part I.

PMID- 17232851
TI  - Description of a Reconstruction of the Head of a Thirty-Millimetre Embryo.

PMID- 17232852
TI  - Two Cases of Wormian Bones in the Bregmatic Fontanelle.

PMID- 17232853
TI  - On Some Morphological Aspects of Microcephalic Idiocy.

PMID- 17232854
TI  - Neutral-Tinted Glycerine-Jelly as a Medium for the Mounting of Pathological
      Specimens.

PMID- 17232855
TI  - A Note on Sections of the Lips of the Primates.

PMID- 17232856
TI  - An Inquiry into the Anatomy and Pathology of the Maxillary Sinus.

PMID- 17232857
TI  - A Description of the Histology of the Eyes in Two Anencephalic Foetuses.

PMID- 17232858
TI  - On the Relation of the Limb Plexuses to the Ribs and Vertebral Column.

PMID- 17232859
TI  - Anatomical Notes.

PMID- 17232860
TI  - Note on a New Expedient for improving the Colour-Injection of Dissection
      Cadavera.

PMID- 17232861
TI  - Apparent Triplication of the Apex of the Right Lung.

PMID- 17232862
TI  - The Effects of Formalin Hardening and the Persistence of Irritability in the
      Muscular Coats of the Intestine.

PMID- 17232863
TI  - A Case of Unilateral Aplasia of the Kidney in a Rabbit.

PMID- 17232864
TI  - The Limb Arteries of Primates.

PMID- 17232865
TI  - On a Method of Mounting and Exhibiting Frozen Sections of the Cadaver in the
      Anatomical Museum.

PMID- 17232866
TI  - On the Injection of Lymphatics by Prussian Blue.

PMID- 17232867
TI  - Supernumerary Kidney: The Occurrence of Three Kidneys in an Adult Male Subject.

PMID- 17232868
TI  - A Contribution to the Development of the Prostate Gland in the Human Female, and
      a Study of the Homologies of the Urethra and Vagina of the Sexes.

PMID- 17232869
TI  - A Ligament acting as a Check to the Action of the Levator Palpebrae Superioris
      Muscle.

PMID- 17232871
TI  - Multiple Anomaly in a Vertebral Column.

PMID- 17232870
TI  - A Human Cranium with an Osseous Tumour of the Frontal Region and a Shallow
      Pituitary Fossa.

PMID- 17232872
TI  - Some Notes on the Epiphyses of the Ribs.

PMID- 17232874
TI  - Report on an Abnormal First Thoracic Vertebra.

PMID- 17232873
TI  - Anatomical Notes.

PMID- 17232875
TI  - Some Points in the Anatomy of the Intracranial Blood-Sinuses.

PMID- 17232876
TI  - Studies of the Intestine and Peritoneum in the Human Foetus: Part I.

PMID- 17232877
TI  - Descriptions of Two Brains of Natives of India.

PMID- 17232878
TI  - The Relations of the Main Divisions of the Trifacial Nerve.

PMID- 17232879
TI  - The Pharyngeal End of Rathke's Pouch.

PMID- 17232880
TI  - A Note on Abnormal Right Subclavian Artery.

PMID- 17232881
TI  - Note on the Reputed Passage of Abnormal Right Subclavian Artery (a) in Front of
      the Trachea, (b) between the Trachea and OEsophagus.

PMID- 17232882
TI  - Note on Accessory Articular Facets between the Sacrum and Ilium, and their
      Significance.

PMID- 17232883
TI  - The Lamina Terminalis and its Relation to the Fornix System.

PMID- 17232884
TI  - A Case in which the Right Ureter passed behind the Inferior Vena Cava: with a
      Short Note upon a Case in which the Left Renal Vein passed behind the Abdominal
      Aorta, and the bearing of these Abnormalities on the Development of the Abdominal
      Veins.

PMID- 17232885
TI  - Description of a Human Skull dredged up in the North Sea off the Coast of
      Norfolk.

PMID- 17232886
TI  - On the Form of the Parotid Gland.

PMID- 17232887
TI  - On the Reconstruction of the Norma Facialis and Verticalis of the Skull.

PMID- 17232888
TI  - Variations of the First Rib, associated with Changes in the Constitution of the
      Brachial Plexus.

PMID- 17232889
TI  - Report upon an Acromegalic Skeleton.

PMID- 17232890
TI  - The Relations of the Thoracic Operculum considered in reference to the Anatomy of
      Cervical Ribs of Surgical Importance.

PMID- 17232891
TI  - The Development of the Ear-Bones in the Mouse.

PMID- 17232892
TI  - Studies in the Embryology of the Ferret.

PMID- 17232893
TI  - Reconstruction of the Head End of an Early Ferret Embryo.

PMID- 17232894
TI  - A Preliminary Communication on the Formation of the Nasal Cavities.

PMID- 17232895
TI  - On the Morphogenesis of the Head of the Crocodile (Crocodilus porosus).

PMID- 17232896
TI  - The Development of the Human Maxilla, Vomer, and Paraseptal Cartilages.

PMID- 17232897
TI  - Studies of the Intestine and Peritoneum in the Human Foetus: Part II.

PMID- 17232898
TI  - Persistence of the Left Posterior Cardinal Vein.

PMID- 17232899
TI  - Types of Nuchal Hair and a Possible Theory of the Prediction of Sex.

PMID- 17232900
TI  - On a Tubercle on the Malar Bone, and on the Lateral Attachments of the Tarsal
      Plates.

PMID- 17232901
TI  - Complete Unilateral Interruption of the Fissure of Rolando.

PMID- 17232902
TI  - Irregular Ossifications in the Space between the Transverse Process and the Rib
      at the Junction of the Neck and Thorax.

PMID- 17232903
TI  - Anatomical Notes.

PMID- 17232904
TI  - Remarks on Fifteen Years of Anthropometric Work in the University of Aberdeen.

PMID- 17232905
TI  - The Subscapularis Muscle.

PMID- 17232906
TI  - A Description of Teeth of Palaeolithic Man from Jersey.

PMID- 17232907
TI  - Cranium of a Young Orang, showing Bilateral and Symmetrical Complete Bipartite
      Division of the Parietals.

PMID- 17232908
TI  - Cranium of a Chimpanzee, showing Metopic Suture; also Fontanelle and Sutural Bone
      Plates.

PMID- 17232909
TI  - An Instance of the Retractor Bulbi Muscle in Man.

PMID- 17232910
TI  - Some Markings on the Cervical Vertebrae.

PMID- 17232911
TI  - Further Researches on the Rods and Cones of Vertebrate Retinae.

PMID- 17232912
TI  - Remarks on Some Points in the Fissuration of the Cerebrum.

PMID- 17232914
TI  - Report on a Skull from British East Africa.

PMID- 17232913
TI  - Notes on the Technical Difficulties of Wax-Plate Reconstruction.

PMID- 17232915
TI  - On the Natural Repair of Fractures, as seen in the Skeletons of Anthropoid Apes.

PMID- 17232916
TI  - A Case of Multiple Heart Anomalies.

PMID- 17232917
TI  - A Case of Abnormal Distribution of the N. Musculo-Cutaneus, with Complete Absence
      of the Ramus Cutaneus N. Radialis.

PMID- 17232918
TI  - The Topographical Anatomy of the Salivary Glands.

PMID- 17232919
TI  - The Influence of Sex on the Position and Composition of the Human Sacrum.

PMID- 17232920
TI  - Extroversion of the Bladder and some Problems in connexion with it.

PMID- 17232921
TI  - The Limb Arteries of Primates.

PMID- 17232922
TI  - Six Specimens of Abnormal Heart.

PMID- 17232923
TI  - Description of an Ashanti Skull with Defective Dentition.

PMID- 17232924
TI  - A Case of Left Inferior Vena Cava occurring in a Female Subject in whom the Left
      Superior Intercostal Vein joined the Vena Azygos Major, and the Twelfth Ribs were
      Absent.

PMID- 17232925
TI  - On the Grooves upon the Ossa Parietalia commonly said to be caused by the Arteria
      Meningea Media.

PMID- 17232926
TI  - Notes on the Folds of Peritoneum connected to the Appendix, and a Caeco
      Appendicular Fold.

PMID- 17232927
TI  - "Cervical Rib": Factors controlling its Presence and its Size. Its Bearing on the
      Morphology and Development of the Shoulder.

PMID- 17232928
TI  - Further Observations on the Rectum and Anal Canal.

PMID- 17232929
TI  - A Case of Hermaphroditism in the Pig.

PMID- 17232930
TI  - A Case of Supernumerary Kidney.

PMID- 17232931
TI  - On the Innervation of the Sino-Auricular Node (Keith-Flack) and the Auriculo
      Ventricular Bundle (Kent-His).

PMID- 17232933
TI  - The Origin of the Vertebrate Limb.

PMID- 17232932
TI  - The Sudbury Calvaria: A Revised and Extended Description.

PMID- 17232934
TI  - On Contour Diagrams of the Mandible.

PMID- 17232935
TI  - Spina Bifida in the Neck Region of a Ferret Embryo 8 mm. long.

PMID- 17232936
TI  - Studies of the Intestine and Peritoneum in the Human Foetus: Part III.

PMID- 17232937
TI  - A Further Communication on the Formation of the Nasal Cavities.

PMID- 17232938
TI  - Absence of the Auditory Canal, and other Anomalies of the External Ear.

PMID- 17232939
TI  - Anatomical Notes.

PMID- 17232940
TI  - The Ribs in the Second Month of Development.

PMID- 17232941
TI  - Some Muscular Anomalies in the Lower Limb.

PMID- 17232943
TI  - The Bury St Edmunds Cranial Fragment.

PMID- 17232942
TI  - Further Observations on the Development of the Sympathetic Nervous System in the
      Chick.

PMID- 17232944
TI  - The Innervation of the Achselbogen Muscle.

PMID- 17232945
TI  - On Some Points in the Anatomy of the Plica Vocalis.

PMID- 17232946
TI  - Note on a Variable Feature of the Astragalus.

PMID- 17232947
TI  - The Abdomino-Pelvic Cavity.

PMID- 17232948
TI  - The Origin of the Osteoblast and of the Osteoclast.

PMID- 17232949
TI  - A Preliminary Communication on the Development and Growth of Bone and the
      Relations thereto of the several Histological Elements concerned.

PMID- 17232950
TI  - Abnormal Crania-Achondroplastic and Acrocephalic.

PMID- 17232951
TI  - Gastro-Pancreatic Folds: their Relation to the Movements of the Stomach and to
      the Subdivisions of the Lesser Sac.

PMID- 17232952
TI  - The Development and Ossification of the Human Clavicle.

PMID- 17232954
TI  - On a Method on Reconstructions by Contour Figure.

PMID- 17232953
TI  - Anomaly of the Vena Cava Inferior; with a Note on the Relationships which help to
      determine the Nature of Anomalies of some of the Abdominal Systemic Veins.

PMID- 17232955
TI  - The Arterial Lesion in Cases of "Cervical" Rib.

PMID- 17232956
TI  - Studies of the Intestine and Peritoneum in the Human Foetus: Part IV.

PMID- 17232957
TI  - Studies of the Intestine and Peritoneum in the Human Foetus: Part V.

PMID- 17232958
TI  - The Functional History of the Coelom and the Diaphragm.

PMID- 17232959
TI  - On the Length of Muscle-Fibres and its Meaning in Physiology and Pathology.

PMID- 17232960
TI  - The Central Fissure of the Cerebrum.

PMID- 17232961
TI  - An Apparent Third Testicle consisting of a Scrotal Spleen.

PMID- 17232962
TI  - Note on a Human Foetal Skull, apparently the Subject of Cephalocele.

PMID- 17232963
TI  - Some Points in the Surgical Anatomy of the Rectum.

PMID- 17232964
TI  - The Form of the Human Stomach.

PMID- 17232966
TI  - Anatomical Note.

PMID- 17232965
TI  - The Causation of the Condition known as Achondroplasia.

PMID- 17232967
TI  - The Morphology of the Sulcus Interparietalis (B.N.A.).

PMID- 17232968
TI  - The Arrangement of the Longitudinal and Circular Musculature at the Upper End of
      the OEsophagus.

PMID- 17232970
TI  - On a Bone found in the Musculus Vastus Externus of the Thigh.

PMID- 17232969
TI  - Notes on the Comparative Anatomy of the Middle Ear.

PMID- 17232971
TI  - Notes on the Dissection of an Agnathic Foetus.

PMID- 17232972
TI  - Duplication of the Post-Renal Segment of the Vena Cava Inferior.

PMID- 17232973
TI  - A Case of Hydrocephalus in an Egyptian of the Roman Period.

PMID- 17232974
TI  - The Auriculo-Ventricular Node in a Malformed Heart, with Remarks on its Nature,
      Connexions, and Distribution.

PMID- 17232976
TI  - Studies of the Intestine and Peritoneum in the Human Foetus: Part VI.

PMID- 17232975
TI  - Notes on the Retro-Colic Fossa, Splenic Process of Peritoneum, and Bloodless Fold
      of Treves.

PMID- 17232977
TI  - Anatomical Note.

PMID- 17232979
TI  - Reconstruction in Modelling Clay: A Rapid Method of Plastic Reconstruction from
      Serial Sections.

PMID- 17232978
TI  - On the Innervation of the Nodal Tissue of the Mammalian Heart.

PMID- 17232980
TI  - Congenital Anomalies of the Fifth Lumbar Vertebra and their Consequences.

PMID- 17232981
TI  - A Case of Complete Absence of both Internal Carotid Arteries, with a Preliminary
      Note on the Developmental History of the Stapedial Artery.

PMID- 17232982
TI  - A Case of Congenital Atresia of the Duodenum, accompanied by Volvulus of the
      Ileum.

PMID- 17232983
TI  - Observations upon Cases of Absence of Lacrimal Bones and of Existence of
      Perilacrimal Ossicles.

PMID- 17232984
TI  - Some Points in the Nomenclature of the External Genitalia of the Female.

PMID- 17232985
TI  - A Note on the Significance of Certain Anomalies of the Renal and Spermatic
      Arteries.

PMID- 17232986
TI  - A Swedenborg Mystery: The Rival Skulls.

PMID- 17232987
TI  - Extroversion of the Bladder, complicated by the Presence of Intestinal Openings
      on the Surface of the Extroverted Area.

PMID- 17232988
TI  - Spolia Anatomica.

PMID- 17232989
TI  - Three Examples of a Right Aortic Arch.

PMID- 17232990
TI  - Measurements on a Human Embryo 30 mm. Long.

PMID- 17232991
TI  - A Congenital Abnormality of the Heart and Blood Vessels.

PMID- 17232992
TI  - The Course of the Phrenic Nerve in the Embryo.

PMID- 17232993
TI  - Note on Two Cases of Well-marked Suprasternal Bones.

PMID- 17232994
TI  - The Development of the Lobus Quadratus of the Liver, with Special Reference to an
      Unusual Anomaly of this Lobe in the Adult.

PMID- 17232995
TI  - The Characters of the English Thigh-Bone.

PMID- 17232996
TI  - The Lower Ends of the Wolffian Ducts in a Female Pig Embryo.

PMID- 17232997
TI  - Two Cases of Cardiac Malformation-more especially of the Infundibular Region.

PMID- 17232998
TI  - Figures relative to Congenital Abnormalities of the Upper Urinary Tract, and some
      Points in the Surgical Anatomy of the Kidneys, Ureter, and Bladder.

PMID- 17232999
TI  - Anomaly of the Inferior Vena Cava: Duplication of the Post-Renal Segment.

PMID- 17233000
TI  - A Communication as to the Causation of Large Vascular Grooves found on the Inner
      Aspect of the Os Parietale.

PMID- 17233001
TI  - The Interrelationship of some Trunk Measurements and their Relation to Stature.

PMID- 17233002
TI  - Observations upon Young Human Embryos.

PMID- 17233003
TI  - A Contribution to the Embryology of the Fore-Limb Skeleton.

PMID- 17233004
TI  - On the Topography of the Intracardiac Ganglia of the Rat's Heart.

PMID- 17233005
TI  - The Second Visceral Arch and Groove in the Tubo-Tympanic Region.

PMID- 17233006
TI  - Investigations in the Anatomy of the Palate.

PMID- 17233007
TI  - Parietal Perforation accompanied with Flattening of the Skull in an Ancient
      Egyptian.

PMID- 17233008
TI  - A New Mylometer.

PMID- 17233009
TI  - The Genesis of Jackson's Membrane: Notes on the Genito-Mesenteric Fold of
      Peritoneum and the Supra-Adhesion Foramen.

PMID- 17233011
TI  - Anatomical Note.

PMID- 17233010
TI  - The Anatomy of the Head End of a 20-mm. Human Embryo.

PMID- 17233012
TI  - The Morphology and Histology of a Human Embryo of 8.5 mm.

PMID- 17233013
TI  - Dental Mutilations in Neolithic Human Remains.

PMID- 17233014
TI  - The Supracondyloid Tubercles of the Femur and the Attachment of the Gastrocnemius
      Muscle to the Femoral Diaphysis.

PMID- 17233015
TI  - Note on a Case of Bifid Penis, with Penial Hypospadia.

PMID- 17233016
TI  - A Human Embryo of Twenty-seven Pairs of Somites, Embedded in Decidua.

PMID- 17233017
TI  - A Reconstruction Model of the Right Middle and Inner Ear.

PMID- 17233018
TI  - A Case of Abnormal Disposition of the Peritoneum.

PMID- 17233019
TI  - A Specimen showing Complete Remains of the Left Superior Vena Cava; with a
      Description of a Venule, which Represents the "Lost" Extra-pericardiac Portion of
      the Left Duct of Cuvier.

PMID- 17233020
TI  - A Case of Duplication of the Ureters.

PMID- 17233021
TI  - Congenital Variation of the Pectoral Muscles, with Report of a Case.

PMID- 17233022
TI  - The Human Stomach and the Canalis Gastricus (Lewis).

PMID- 17233023
TI  - A Rare Vascular Anomaly-Opening of the Upper Left Pulmonary Vein into a
      Persistent Left Superior Vena Cava.

PMID- 17233024
TI  - Preliminary Note on a Diarthrodial Articulation between the Clavicle and the
      Coracoid.

PMID- 17233025
TI  - Manifestation of Occipital Vertebrae, and Fusion of the Atlas with the Occipital
      Bone.

PMID- 17233026
TI  - The Cranial Attachment of the Internal Lateral Ligament of the Lower Jaw: with an
      Investigation into the Fibrogenesis of this Structure.

PMID- 17233027
TI  - Some Factors influencing the Position of the Small Intestine.

PMID- 17233029
TI  - Vertebral Column with Six and a Half Cervical and Thirteen True Thoracic
      Vertebrae with Associated Abnormalities of the Cervical Spinal Cord and Nerves.

PMID- 17233028
TI  - A Pleural Fold containing the Vena Azygos.

PMID- 17233030
TI  - Appendices Epiploicae and Pericolic Membranes.

PMID- 17233031
TI  - The Topographical and Applied Anatomy of the Gall-Bladder and Bile-Ducts.

PMID- 17233032
TI  - Observations on Certain Structural Details of the Neck of the Femur.

PMID- 17233033
TI  - The Neck of the Femur as a Static Problem.

PMID- 17233035
TI  - Anatomical Notes.

PMID- 17233034
TI  - (1) Two Cases of Cervical Ribs. (2) An Anomalous Arrangement of the Vagi.

PMID- 17233036
TI  - The Characters of the English Thigh-Bone: Part II: The Difficulty of Sexing.

PMID- 17233037
TI  - Two Cases, considered from the Developmental Standpoint, in which the Right
      Subclavian Artery arose from the Arch of the Aorta beyond the Origin of the Left
      Subclavian Artery; with a Note on the Relation of the Subclavian Veins to the
      Cardinal System.

PMID- 17233038
TI  - Some Rare Muscular Anomalies.

PMID- 17233039
TI  - On the Skeleton of an Ectromelic Goat.

PMID- 17233040
TI  - A Note on the Posterior Cruciate Ligament of the Knee-Joint.

PMID- 17233041
TI  - Bilateral Abnormal Relationship of the Vagus Nerve in its Cervical Portion.

PMID- 17233042
TI  - The Chelonian Type of Genitalia.

PMID- 17233043
TI  - An Anomalous Coronary Sinus.

PMID- 17233044
TI  - Congenital Absence of the Appendix of the Caecum.

PMID- 17233045
TI  - A Case of Congenital Absence of the Left Kidney and Ureter.

PMID- 17233047
TI  - The Epiphysis of the Head of the Femur.

PMID- 17233046
TI  - On the Physiology of the Crucial Ligaments and Semilunar Cartilages of the Knee
      Joint, with a Suggestion of the Origin of some Instances of Haemarthrus and Loose
      Bodies.

PMID- 17233048
TI  - The Homologies of the Chelonian and Mammalian Types of Genitalia.

PMID- 17233049
TI  - Developmental Changes in the Pericardium, the Mesocardia, and the Pleural Sacs in
      the Human Embryo.

PMID- 17233050
TI  - The Mucinous Changes of the Vaginal Epithelium of Certain Mammals in Pregnancy.

PMID- 17233051
TI  - Some Abnormal Developments in the Vascular System of the Frog (Rana temporaria).

PMID- 17233052
TI  - On the Presence of Genial Tubercles on the Mandible of Man, and their Suggested
      Association with the Faculty of Speech.

PMID- 17233053
TI  - On the Factors concerned in causing Rotation of the Intestine in Man.

PMID- 17233054
TI  - Endocranial Casts and Brain Form: A Criticism of some Recent Speculations.

PMID- 17233055
TI  - The Arteries of the Pons and Medulla Oblongata.

PMID- 17233056
TI  - The Costal Musculature.

PMID- 17233057
TI  - The Transition of the Ciliated Epithelium of the Nose into the Squamous
      Epithelium of the Pharynx.

PMID- 17233058
TI  - Hereditary Abnormal Segmentation of the Index and Middle Fingers.

PMID- 17233059
TI  - The Measurement of Diaphysial Growth in Proximal and Distal Directions.

PMID- 17233060
TI  - The Genitalia of Galeopithecus.

PMID- 17233061
TI  - Observations on the Popliteal Groove on the Femur.

PMID- 17233062
TI  - The Structure of the Blastoderm, and the Continuity of the Cell-Elements during
      the Early Stages of Development.

PMID- 17233063
TI  - Two Examples of Cardiac Malformation.

PMID- 17233064
TI  - The Thyroidea Ima Artery.

PMID- 17233065
TI  - The West Scottish Skull.

PMID- 17233066
TI  - The Arteries of the Pons and Medulla Oblongata: Part II.

PMID- 17233067
TI  - Sur la Structure du Poumon du Dauphin (Delphinus delphis).

PMID- 17233069
TI  - Congenital Deficiency of the Pericardium.

PMID- 17233068
TI  - An Unusual Peritoneal Sac.

PMID- 17233070
TI  - The Relation of the Amphibian Parasphenoids.

PMID- 17233071
TI  - Three Cases of Reappearance of Ovarian Peritoneal Sacculation in the Human
      Female.

PMID- 17233072
TI  - Omphalopagous Twins in the Human Subject.

PMID- 17233073
TI  - A Palmaris Longus Muscle with a Reversed Belly, forming an Accessory Flexor
      Muscle of the Little Finger.

PMID- 17233074
TI  - PROCEEDINGS OF THE ANATOMICAL SOCIETY OF GREAT BRITAIN AND IRELAND.

PMID- 17233075
TI  - Melatonin in gastroprotection against stress-induced acute gastric lesions and in
      healing of chronic gastric ulcers.
AB  - The degree of gastric damage following to exposition of the mucosa to noxious
      agents depends upon a balance between the factors promoting this damage and those
      activating the natural defense mechanisms. Recent findings, presented in this
      review, provide evidence that melatonin prevents the formation of acute gastric
      lesions induced by stress and accelerates healing of chronic gastric ulcers due
      to increase in the activity of nitric oxide (NO) synthase (NOS)-NO and
      cyclooxygenase (COX)-prostaglandin E(2) (PGE(2)) systems resulting in the
      increase of mucosal blood flow and mucosal integrity. Melatonin is produced and
      released into the circulation by the pineal gland and, in many times larger
      amounts, by the gastrointestinal tract. Due to its anti-inflammatory and anti
      oxidant properties, melatonin may be one of the most efficient protective factors
      preventing the development of acute gastric damage and accelerating healing of
      chronic gastric ulcers probably due to reduction in proinflammatory cytokine
      production, scavenging of the radical oxygen species and activation of COX-PG and
      NOS-NO systems as well as stimulating the afferent sensory nerves in the brain
      gut axis.

PMID- 17233076
TI  - Beyond coming out: gay men, HIV, and age.

PMID- 17233077
TI  - Making meaning of seroconversion in older gay men.

PMID- 17233079
TI  - In sickness and in health. A conversation about doctor-patient relationships.

PMID- 17233078
TI  - Lessons I learned from Dr. Cruise Control. How one man's search for  a doctor
      taught him to be an active participant in his own health care.

PMID- 17233080
TI  - The 10-point inspection, HIV-style: what to check under the hood. Some of the
      most important tests, and what they mean.

PMID- 17233081
TI  - Helping your antiretrovirals help you. Things to consider when choosing what goes
      in the tank.

PMID- 17233082
TI  - Can it get even better than this? You don't need to trade in for a newer model
      you can live longer and better...while controlling HIV.

PMID- 17233083
TI  - Don't forget your head. Before you get behind the wheel, make sure you are in
      full control.

PMID- 17233084
TI  - XVI International AIDS Conference. New drug classes from Toronto. Plus some older
      ones.

PMID- 17233085
TI  - XVI International AIDS Conference. The miseducation of youth. Arguably biased and
      confusing.

PMID- 17233086
TI  - XVI International AIDS Conference. From the top down. African American leaders
      mobilize to fight AIDS...finally.

PMID- 17233087
TI  - Update from the 5th International AIDS Vaccine Conference. Looking for ways to
      stimulate the immune system.

PMID- 17233088
TI  - Does HIV treatment prevent new infections better than condoms? Examining some
      biological considerations.

PMID- 17233089
TI  - Keeping up the PACE. New York State prison program changes lives.

PMID- 17233091
TI  - 23-plus years survival with fair and better adherence. Poor adherence has less
      than half survival time.

PMID- 17233090
TI  - Program simulates on-the-job education and clinical support for HIV doctors.
      Clinics in African hotspots will use system.

PMID- 17233092
TI  - HIV/AIDS stigma--basic problems remain. Researchers look at long-term of HIV
      prejudice.

PMID- 17233093
TI  - FDA approves generic abacavir sulfate tablets.

PMID- 17233094
TI  - Daily news alerts selected by AIDS Treatment News:
      www.connotea.org/group/aidsnew.
AB  - Now you can follow treatment news as it happens at AIDSNEW, a free service of
      AIDS Treatment News. We select important, quality reports in medical journals,
      AIDS treatment sites, and the general press, and publish Web links to them, all
      in one place at www.connotea.org/group/aidsnew -- often on the first day the news
      is available anywhere. No need to subscribe, register, or log in. Just visit
      http://www.connotea.org/group/aidsnew -- then scroll down and click any of the
      titles for more information. You can use almost any computer and Web browser.

PMID- 17233095
TI  - Resveratrol: why it matters in HIV.
AB  - Large doses of resveratrol (found in small amounts in red wine) made headlines
      recently for extending the lifespan of mice on an unhealthy diet. This and other
      substances found in some wines and foods may protect against cardiovascular
      disease or diabetes, and improve the functioning of mitochondria in cells (which
      could reduce certain adverse effects of HIV or the drugs used to treat it).

PMID- 17233096
TI  - Lung cancer: very high death rate with HIV, huge reduction possible with CT
      screening for early diagnosis.
AB  - Lung cancer has a high death rate, especially with HIV in one group of patients
      studied recently. Researchers are finding that most of the fatalities are due to
      late diagnosis; as many as 80% of the deaths from lung cancer in the general
      population might be prevented by CT screening to find the tumors early. The
      patients with HIV were often relatively healthy, so doctors did not suspect that
      they had cancer.

PMID- 17233097
TI  - 1 in 5 with low CD4 counts not on treatment.

PMID- 17233098
TI  - 'We need a microbicide now!'.

PMID- 17233100
TI  - Serious bacterial infections in children with HIV.

PMID- 17233099
TI  - Microbicides 2006 Conference Opening Address delivered by Graca Machel.

PMID- 17233101
TI  - Focus on hepatitis. HIV/HCV-coinfected may have worse survival.

PMID- 17233102
TI  - Intensified remembering.

PMID- 17233103
TI  - FDA approves new PI.

PMID- 17233104
TI  - ABC in the news.

PMID- 17233106
TI  - Focus on hepatitis. Higher US HCV rate.

PMID- 17233105
TI  - Butting heads with resistance.

PMID- 17233107
TI  - On determining a 1-tailed upper limit for future sample HorRat values.
AB  - Two formulas were developed for use in computing 1-tailed upper limits for future
      HorRat values obtained from the collaborative study of materials. One formula is
      applicable when a future sample HorRat value H [formula: see text] is computed
      based on a known concentration (e.g., C = spike level and RSD(R) is the sample
      relative reproducibility standard deviation) and the other formula is applicable
      when the true concentration (C) is unknown and a future sample HorRat value
      [formula: see text] is computed using the sample mean (e.g., y, the collaborative
      study overall mean for an analyte). A Monte Carlo simulation procedure was
      developed using the Statistical Analysis System (SAS) software to assess the
      accuracy of the 2 developed formulas. Based on the degree of closeness between
      the simulated and calculated limits, the formulas for computing upper limits for
      future sample HorRat values will prove to be useful to Study Directors in
      determining worst case scenarios concerning a method's reproducibility precision
      relative to that predicted using the "Horwitz equation". We also define the
      current empirical HorRat limits as 1-tailed 100p% upper limits to assess the
      statistical consequence, in a probability sense, of their application as an
      analytical methods screening tool.

PMID- 17233108
TI  - Antenatal corticosteroids for accelerating fetal lung maturation for women at
      risk of preterm birth.

PMID- 17233109
TI  - Graham Dixon talks about his career, his involvement with the Society for
      Chemical Industries and the development of SCIpharm2006. Interview by Steve
      Carney.

PMID- 17233110
TI  - [The Danish cooperative dairy industry and the law of evolution, 1950-70].

PMID- 17233111
TI  - [Police sports in Germany from their beginnings during the German empire to the
      end of National Socialism].

PMID- 17233112
TI  - [A woman with stomach pain previously surgically treated for morbid obesity].

PMID- 17233113
TI  - [Complications after surgery for obesity].

PMID- 17233114
TI  - The disordered amino-terminus of SIMPL interacts with members of the 70-kDa heat
      shock protein family.
AB  - The p65 coactivator SIMPL is a small protein that lacks any conserved domains of
      known function. To better understand regulation of SIMPL activity, we sought to
      identify novel SIMPL interacting proteins using mass spectrometry analysis of
      SIMPL containing complexes. Two members of the 70-kDa heat-shock protein family,
      Hsp70 and Hsc70, were identified as SIMPL binding proteins. Subsequent
      immunocomplexing assays confirmed this interaction and demonstrated that the
      amino-terminus of SIMPL is required for this interaction. Using a combination of
      amino acid composition analysis, PONDR VL-XT prediction, charge-hydropathy plots,
      and cumulative distribution functions, the amino-terminal region of both mouse
      and human SIMPL proteins was predicted to be intrinsically disordered. These
      data, taken together, suggest that Hsp70/Hsc70 bind the intrinsically disordered
      amino-terminal region of SIMPL to stabilize the protein and thereby regulate its
      activity. Understanding the regulation of SIMPL through its interaction with
      Hsp70/Hsc70 may serve as a novel means of modulating tumor necrosis factor alpha
      signaling.

PMID- 17233115
TI  - Correction: notice of duplicate publication.

PMID- 17233116
TI  - Electrogene therapy with p53 of murine sarcomas alone or combined with
      electrochemotherapy using cisplatin.
AB  - The aim of our study was to evaluate feasibility and therapeutic potential of
      electrogene therapy with p53 alone or combined with electrochemotherapy using
      cisplatin on two murine sarcomas with different p53 status. Antitumor
      effectiveness of three consecutive electrogene treatments with p53 was more
      effective in wild-type LPB tumors than mutated SA-1 tumors, resulting in 21.4% of
      tumor cures in LPB tumors and 12.5% in SA-1 tumors. Pretreatment of tumors with
      electrogene therapy with p53 enhanced chemosensitivity of both tumor models
      treated by electrochemotherapy with cisplatin. After only one application of this
      treatment combination in the LPB tumor model, specific tumor growth delay was
      prolonged in the combined treatment group compared to electrogene therapy with
      p53 or electrochemotherapy with cisplatin alone, whereas in SA-1 tumors this
      treatment combination resulted in 31.6% of cured animals. Results of our study
      show that electrogene therapy with p53 alone or combined with electrochemotherapy
      is feasible and effective treatment of tumors. The combination of electrogene
      therapy and electrochemotherapy after only one application resulted in complete
      regression of tumors.

PMID- 17233117
TI  - The pro-inflammatory cytokines, IL-1beta and TNF-alpha, inhibit intestinal
      alkaline phosphatase gene expression.
AB  - High levels of the pro-inflammatory cytokines, interleukin-1beta (IL-1beta) and
      tumor necrosis factor-alpha (TNF-alpha), are present in the gut mucosa of
      patients suffering form various diseases, most notably inflammatory bowel
      diseases (IBD). Since the inflammatory milieu can cause important alterations in
      epithelial cell function, we examined the cytokine effects on the expression of
      the enterocyte differentiation marker, intestinal alkaline phosphatase (IAP), a
      protein that detoxifies bacterial lipopolysaccharides (LPS) and limits fat
      absorption. Sodium butyrate (NaBu), a short-chain fatty acid and histone
      deacetylase (HDAC) inhibitor, was used to induce IAP expression in HT-29 cells
      and the cells were also treated +/- the cytokines. Northern blots confirmed IAP
      induction by NaBu, however, pretreatment (6 h) with either cytokine showed a dose
      dependent inhibition of IAP expression. IAP Western analyses and alkaline
      phosphatase enzyme assays corroborated the Northern data and confirmed that the
      cytokines inhibit IAP induction. Transient transfections with a reporter plasmid
      carrying the human IAP promoter showed significant inhibition of NaBu-induced IAP
      gene activation by the cytokines (100 and 60% inhibition with IL-1beta and TNF
      alpha, respectively). Western analyses showed that NaBu induced H4 and H3 histone
      acetylation, and pretreatment with IL-1beta or TNF-alpha did not change this
      global acetylation pattern. In contrast, chromatin immunoprecipitation showed
      that local histone acetylation of the IAP promoter region was specifically
      inhibited by either cytokine. We conclude that IL-1beta and TNF-alpha inhibit
      NaBu-induced IAP gene expression, likely by blocking the histone acetylation
      within its promoter. Cytokine-mediated IAP gene silencing may have important
      implications for gut epithelial function in the setting of intestinal
      inflammatory conditions.

PMID- 17233118
TI  - [The development of Swiss company soccer, 1920-55].

PMID- 17233119
TI  - [Measurement of source strength for 192Ir HDR RALS].

PMID- 17233120
TI  - [Clinical trials on radiation oncology in Japan].

PMID- 17233121
TI  - [Application of Monte Carlo stimulation for radiation therapy: on the features of
      EGS4 and BEAMnrc code].

PMID- 17233122
TI  - Rapid emergence of methicillin-resistant Staphylococcus aureus (MRSA) among
      children and adolescents in northern Manitoba, 2003-2006.

PMID- 17233123
TI  - [Revolution in radiation therapy: TomoTherapy HI-ART system].

PMID- 17233124
TI  - Outbreak of Escherichia coli O157:H7 gastroenteritis associated with consumption
      of beef donairs, Edmonton, Alberta, May-June 2006.

PMID- 17233125
TI  - [Monte Carlo simulation: the calculation algorithm for next generation RTP
      system].

PMID- 17233126
TI  - [The performance of stereotactic radiotherapy].

PMID- 17233127
TI  - [Transition of ionization chambers and various detectors].

PMID- 17233128
TI  - [The Jews in Moravia in the modern period as a specific cultural, social, and
      reproductive minority].

PMID- 17233129
TI  - [Outline of the legal restrictions to the electronic media on official documents
      regarding radiation safety management].

PMID- 17233130
TI  - [Questions and answers on PET facilities: part 4].

PMID- 17233131
TI  - [From the memoirs of the middle classes (Czech Lands, 1935-45)].

PMID- 17233132
TI  - Tight deadline for comments on tail docking legislation.

PMID- 17233133
TI  - UEVP considers the value of pets to Europe's economies.

PMID- 17233134
TI  - The illusion of inclusion: the political significance of women's groups in
      Hungary.

PMID- 17233135
TI  - Women in technological higher education and in the sciences in 20th century
      Hungary.

PMID- 17233136
TI  - Women's rights in Stalinist Hungary: the abortion trials of 1952-53.

PMID- 17233137
TI  - [Between appearance and actuality].

PMID- 17233139
TI  - [Effects of implementing DRG in the hospital. Study indicates changes in nursing
      since conversion to lump sum reimbursement].

PMID- 17233140
TI  - [Changed guidelines for resuscitation: simpler clinical pathways for improved
      survival].

PMID- 17233141
TI  - [Drug administration by gastrostomy tube].

PMID- 17233142
TI  - ["Fast track" in visceral surgery--2: Operation and pain therapy: preventing
      discomfort and added illness perception].

PMID- 17233143
TI  - [Professional nursing dialogue instead of nursing rounds--project report:
      targeted communication promotes patient-centered nursing].

PMID- 17233144
TI  - [Health promotion in nursing between claims and reality--6: Women and health].

PMID- 17233145
TI  - [Pressure ulcer prevalence in Germany: results of a cross-sectional study in
      2006].
AB  - In April 2006 the sixth study to survey the prevalence of nursing-related health
      problems in German hospitals and nursing homes was conducted. In total 7107
      persons partcipated in this study. The pressure ulcer prevalence was calculated
      for the participants who were assessed to be at pressure ulcer risk. In nursing
      homes the prevalence was 8.3 percent, in hospitals 15.1 percent of patients at
      risk showed at least one pressure ulcer. Although the proportion of persons at
      risk did not alter during the last five years, the prevalence decreased within
      this time. Therefore one can assume that the quality of pressure ulcer prevention
      and therapy has been improved.

PMID- 17233146
TI  - [New methods for managing patients with vascular disease--3: Assessing quality of
      life opens new perspectives].

PMID- 17233148
TI  - [Development of a candidate selection method for education: decisions should rest
      on achievable competences].

PMID- 17233147
TI  - [Constructing case situations for learning counseling competence: contents and
      aspects of methodological building blocks].

PMID- 17233149
TI  - [Freedom of opinion in occupational law: Wistleblowing--the end of responsibility
      for secrecy].

PMID- 17233150
TI  - [From case to case: an aid is not necessarily aid].

PMID- 17233151
TI  - [Recognizing and understanding disorders: dyspnea symptoms].

PMID- 17233152
TI  - [New kind of stocking system simplifies compression therapy].

PMID- 17233153
TI  - Comparison of AR and Welch methods in epileptic seizure detection.
AB  - Brain is one of the most critical organs of the body. Synchronous neuronal
      discharges generate rhythmic potential fluctuations, which can be recorded from
      the scalp through electroencephalography. The electroencephalogram (EEG) can be
      roughly defined as the mean electrical activity measured at different sites of
      the head. EEG patterns correlated with normal functions and diseases of the
      central nervous system. In this study, EEG signals were analyzed by using
      autoregressive (parametric) and Welch (non-parametric) spectral estimation
      methods. The parameters of autoregressive (AR) method were estimated by using
      Yule-Walker, covariance and modified covariance methods. EEG spectra were then
      used to compare the applied estimation methods in terms of their frequency
      resolution and the effects in determination of spectral components. The
      variations in the shape of the EEG power spectra were examined in order to
      epileptic seizures detection. Performance of the proposed methods was evaluated
      by means of power spectral densities (PSDs). Graphical results comparing the
      performance of the proposed methods with that of Welch technique were given. The
      results demonstrate consistently superior performance of the covariance methods
      over Yule-Walker AR and Welch methods.

PMID- 17233154
TI  - How responsive Turkish health care system is to its citizens: the views of
      hospital managers.
AB  - With this paper it was tried to give a broad perspective about the responsiveness
      level of Turkish health care system, and how Turkish health care system meets the
      expectations of its citizens. For achieving the main purpose of this study a
      sample of hospital managers (n = 172) was selected, and the responsiveness
      questionnaire developed by WHO was administered. If the responsiveness level of
      Turkish health care system is measured on the basis of the Turkish hospital
      managers' views in the sample by using the weights reported in the World Health
      Report 2000, responsiveness level is calculated as 6.14, and Turkey's place
      should be 35 rather than 93 among 191 countries. The findings showed that Turkish
      health care system met confidentiality expectations of Turkish citizens better
      than other expectations for other aspects of responsiveness. In light of the main
      results of this study we conclude that the economic status, demographic
      structure, culture, and some other regional and country-specific factors should
      be taken into account by calculating and especially ranking the countries
      according to responsiveness level of their health care systems, and each country
      should carry out this kind of studies by using the views of their own key
      informants or preferably citizens, if possible.

PMID- 17233155
TI  - Clinical information system availability and use in urban and rural hospitals.
AB  - Clinical information systems (CIS) capture clinical data to support more
      efficient and effective decision making and clinical care delivery. Only a few
      estimates of CIS availability and use in hospitals are available nationally. The
      purpose of the current research is to examine differences in CIS availability and
      use between urban and rural hospitals. A survey addressing this purpose was
      completed by 74 (63.7%) of Iowa hospitals. Rural hospitals lag behind urban
      hospitals in terms of many CIS applications. More than 80% of the urban
      hospitals, but only between 30 and 40% of the rural hospitals, reported using
      computers to collect basic clinical information for potential use in an
      electronic medical record (EMR) and computerized provider order entry (CPOE)
      system. Comparison of CIS within one state's urban and rural hospitals sheds
      light on variation in clinical support applications, decision support, and
      electronic medical record "readiness" in these settings.

PMID- 17233156
TI  - Context based error modeling for lossless compression of EEG signals using neural
      networks.
AB  - Two-stage lossless data compression methods involving predictors and encoders are
      well known. This paper discusses the application of context based error modeling
      techniques for neural network predictors used for the compression of EEG signals.
      Error modeling improves the performance of a compression algorithm by removing
      the statistical redundancy that exists among the error signals after the
      prediction stage. In this paper experiments are carried out by using human EEG
      signals recorded under various physiological conditions to evaluate the effect of
      context based error modeling in the EEG compression. It is found that the
      compression efficiency of the neural network based predictive techniques is
      significantly improved by using the error modeling schemes. It is shown that the
      bits per sample required for EEG compression with error modeling and entropy
      coding lie in the range of 2.92 to 6.62 which indicates a saving of 0.3 to 0.7
      bits compared to the compression scheme without error modeling.

PMID- 17233157
TI  - Barcode technology in blood bank information systems: upgrade and its impact.
AB  - This paper desires to explore the role of barcode technology in blood bank
      information systems via addressing its upgrade and the consequent impact.
      Firstly, it briefs the application and effect of barcode technology in blood
      donation and transfusion service. In the second, the barcode paradigms of Macau
      Codabar and ISBT 128 are carefully examined and compared in accordance with the
      procedure and specifications of barcode upgrade. Then, the impact due to upgrade
      is assessed from the perspectives of blood bank information system, blood banks,
      and even blood donation and transfusion service. It finally discusses the
      considerations on implementing the upgrade of barcode technology in blood bank
      information systems.

PMID- 17233158
TI  - French claims data as a source of information to describe cancer incidence:
      predictive values of two identification methods of incident prostate cancers.
AB  - Claims data from the "Programme de Medicalisation du Systeme d'Information"
      (PMSI) have been commonly used for several years to complement cancer registries
      and describe cancer incidence in France. It is less clear whether or not it is
      possible to use these data as an independent source of information to assess
      cancer incidence, in the absence of a regional cancer registry. Following a
      similar study on breast cancer, we present a study which aimed to evaluate two
      methods of identifying incident prostate cancer using claims data. These methods
      were developed using claims data from the Hospices Civils de Lyon (HCL) and their
      validity was tested against medical records. The first method (M1) identified
      incident patients as those who had at least one stay with a principal diagnosis
      of prostate cancer. The second method (M2) had a prostate cancer treatment code
      in addition to the criteria for the first method. Both methods of identification
      had similar results, indicating a low rate of false negatives (negative
      predictive values: M1 = 100 [CI95: 93.8-100], M2 = 98.6 [CI95: 90.1-99.6]) and a
      high rate of false positives (positive predictive values: M1 = 33.3 [CI95: 23.2
      42.1], M2 = 33.7 [CI95: 24.2-43.2]). The sample size did not allow us to produce
      consistent estimates of sensitivity and specificity. Our results showed that an
      estimation of the number of incident cases of prostate cancer using both methods
      of identification would be biased because of the high rate of false positives.
      Statistical methods that correct identification errors should be used.

PMID- 17233159
TI  - Suppression of impulse noise in medical images with the use of Fuzzy Adaptive
      Median Filter.
AB  - A new rule based fuzzy filter for removal of highly impulse noise, called Rule
      Based Fuzzy Adaptive Median (RBFAM) Filter, is aimed to be discussed in this
      paper. The RBFAM filter is an improved version of Adaptive Median Filter (AMF)
      and is presented in the aim of noise reduction of images corrupted with additive
      impulse noise. The filter has three stages. Two of those stages are fuzzy rule
      based and last stage is based on standard median and adaptive median filter. The
      proposed filter can preserve image details better then AMF while suppressing
      additive salt & pepper or impulse type noise. In this paper, we placed our
      preference on bell-shaped membership function instead of triangular membership
      function in order to observe better results. Experimental results indicates that
      the proposed filter is improvable with increased fuzzy rules to reduce more noise
      corrupted images and to remove salt and pepper noise in a more effective way than
      what AMF filter does.

PMID- 17233160
TI  - Efficient management of health centres human resources in Zambia.
AB  - This study uses Data Envelopment Analysis (DEA) to estimate the degree of
      technical, allocative and cost efficiency in individual public and private health
      centres in Zambia; and to identify the relative inefficiencies in the use of
      various inputs among individual health centers. About 83% of the 40 health
      centres were technically inefficient; and 88% of them were both allocatively and
      cost inefficient. The privately owned health centers were found to be more
      efficient than public facilities.

PMID- 17233161
TI  - Combining neural network models for automated diagnostic systems.
AB  - This paper illustrates the use of combined neural network (CNN) models to guide
      model selection for diagnosis of internal carotid arterial (ICA) disorders. The
      ICA Doppler signals were decomposed into time-frequency representations using
      discrete wavelet transform and statistical features were calculated to depict
      their distribution. The first level networks were implemented for the diagnosis
      of ICA disorders using the statistical features as inputs. To improve diagnostic
      accuracy, the second level network was trained using the outputs of the first
      level networks as input data. The CNN models achieved accuracy rates which were
      higher than that of the stand-alone neural network models.

PMID- 17233162
TI  - On the creation of a new diagnostic model for fetal well-being on the base of
      wavelet analysis of cardiotocograms.
AB  - The article is devoted to the description of the results of wavelet analysis of
      fetal heart rate detecting by cardiotocography method. A number of conclusions
      are made on the base of such an analysis. It is a part of the research program of
      creation of a new diagnostic model estimating fetal conditions in antepartum
      period.

PMID- 17233163
TI  - The preventive specialist.

PMID- 17233164
TI  - Effectiveness of antimicrobial mouthrinses on aerosols produced by an air
      polisher.
AB  - PURPOSE: The purpose of this examiner-blind investigation was to study the effect
      of two antimicrobial mouthrinses on the quantity and potential respiratory
      penetrating ability of microorganisms generated by an air-abrasive polisher.
      METHODS: Forty-five adult subjects were randomly assigned to one of three groups
      and asked to rinse for 30 seconds with 15 ml of either a 0.12% chlorhexidine
      rinse, an essential oil mouthrinse, or water prior to air polishing. Prior to
      treatment, microbes in ambient air were collected for five minutes using an
      Andersen air sampler. This device simulates the human respiratory system and
      collects airborne microbes by means of blood agar plates stacked in a cascade
      impact system. Bacteria found at stages two, four, and six--representing the
      pharynx, bronchi, and alveoli-were collected and counted in this study. During
      three minutes of air-abrasive instrumentation and two minutes immediately
      following, airborne microbes were again collected. Agar plates removed from the
      sampler were incubated for 24 hours at 37 degrees C. Colony-forming units per
      cubic foot of air (CFUs/ft(3)) were enumerated using a Lab Line colony counter.
      Data were analyzed using a two-factor repeated measure ANOVA and Dunn's multiple
      mean comparison techniques. RESULTS: Results showed no significant effect of
      prerinsing among treatment groups. An increase in CFUs/ft(3) was found at each
      sequential stage of the air sampler, resulting in a statistically significant
      within-group effect (p< or =.05). Additionally, a significant interaction was
      found between prerinse treatment and respiratory stage (p< or =.05) . CONCLUSION:
      While the air-abrasive polisher produced significant amounts of deeply
      penetrating bacterial aerosol, differences in CFUs/ft(3) generated following the
      antimicrobial prerinsing tested are of little clinical significance.

PMID- 17233165
TI  - Dental hygienists' career promotional behaviors and attitudes.
AB  - PURPOSE: The purpose of this study was to examine dental hygienists' career
      promotional behavior and factors which influence such behavior, including the
      image of dental hygiene, career and job satisfaction, the market demand for
      dental hygienists, and the influence of professional affiliation. Relationships
      between demographic items and promotional behaviors also were determined.
      METHODS: In fall 1990, a 48-item survey was mailed to a random sample of 600
      dental hygienists living in Virginia. Responses were analyzed by Pearson
      correlation coefficient, t-test, and analysis of variance RESULTS: A 61.5%
      response rate was obtained (N=368). The majority of respondents (79%) promote
      dental hygiene as a desirable career with the career and job satisfaction factor
      having the highest correlation (r=.69, p<.001) with dental hygienists'
      promotional behaviors. Of the demographic variables, years in practice, age, and
      years since graduation were negatively correlated with dental hygienists'
      promotional behaviors. CONCLUSIONS: Dental hygiene practitioners hold the
      potential for promoting careers in dental hygiene as well as for promoting their
      profession. Dental hygienists who are satisfied with their career and job
      situation are more likely to promote dental hygiene as a desirable profession.

PMID- 17233166
TI  - A proposed human needs conceptual model for dental hygiene: part I.
AB  - To date, research and theory development in dental hygiene have been largely
      sporadic and lacking in focus. Dental hygiene has begun to develop its body of
      knowledge by adopting a definition of the discipline and a structural hierarchy
      of knowledge that includes a global paradigm, conceptual model(s), and theory. By
      identifying major concepts and linking theory to an expanding knowledge base,
      dental hygiene can begin to evolve as a scientific discipline. Conceptual models
      and theories will characterize the uniqueness of dental hygiene and move it into
      collegiality with other professional disciplines. In the future, practitioners,
      educators, and researchers may adopt an organizational framework for dental
      hygiene. Doing so will enhance dental hygiene research, teaching, and client
      care. Most importantly, it will enhance dental hygiene's view of itself. This in
      turn will facilitate dental hygiene's continuing evolution toward
      professionalization.

PMID- 17233167
TI  - Application of the human needs conceptual model of dental hygiene to the role of
      the clinician : part II.
AB  - In summary, the theories of Maslow and of Yura and Walsh have been highlighted as
      background for understanding the human needs conceptual model of dental hygiene.
      In addition, 11 human needs have been identified and defined as being especially
      related to dental hygiene care, and a sample evaluation tool for their clinical
      assessment and a dental hygiene care plan have been presented. The four concepts
      of client, environment, health/oral health, and dental hygiene actions explained
      in terms of human need theory, and the 11 human needs related to dental hygiene
      care constitute the human needs conceptual model of dental hygiene. Within the
      framework of the human needs conceptual model of dental hygiene, the dental
      hygiene process is a systematic approach to dental hygiene care that involves
      assessment of the 11 human needs related to dental hygiene care; analysis of
      deficits in these needs; determination of the dental hygiene care plan based on
      identified deficits; implementation of dental hygiene interventions stated in the
      care plan; and evaluation of the effectiveness of dental hygiene interventions in
      achieving specific goals, including subsequent reassessment and revision of the
      dental hygiene care plan. This human needs conceptual model for dental hygiene
      provides a guide for comprehensive and humanistic client care. This model allows
      the dental hygienist to view each client (whether an individual or a group)
      holistically to prevent oral disease and to promote health and wellness. Dental
      hygiene theorists are encouraged to expand this model or to develop additional
      conceptual models based on dental hygiene's paradigm.

PMID- 17233168
TI  - Self-determination.

PMID- 17233169
TI  - Effects of air-powder polishing on the bond strength of orthodontic bracket
      adhesive systems.
AB  - PURPOSE: The purpose of this in vitro investigation was to evaluate the effects
      of air-powder polishing on the shear bond strength of two adhesive systems used
      for direct orthodontic bracket bonding. METHODS: Ninety-six third molar teeth
      were randomly assigned to be bonded with metal brackets using either a no-mix
      (System 1+) or a two-paste (Concise) orthodontic adhesive resin. Twelve samples
      in each test group were air-powder polished for either 0, 15, 30, or 60 seconds.
      The shear bond strength was determined for each bracket using the Instron.
      Scanning electron microscopy determined bond fracture patterns of tested samples.
      RESULTS: Mean shear bond strength values from baseline to 60 seconds varied from
      22.9+/-1.9 megapascal units (MPa) to 18.2+/-4.1 MPa for Concise and from 15.5+/
      2.1 MPa to 14.6+/-1.9 MPa for System 1+. A two-factor analysis of variance showed
      air-powder polishing significantly affected the mean shear bond strength of one
      adhesive. Results showed a significant decrease (p < or = .05) in the mean shear
      bond strength of the Concise adhesive at 60 seconds of air-powder polishing when
      compared to the 0-, 15-, and 30-second treatments. No significant within group
      time effect of air-powder polishing was found for System 1+. Differences in the
      fracture pattern of the Concise 60-second air-powder polishing group may account
      for the decrease in mean bond strength seen after treatment. CONCLUSION: Although
      in vitro results showed decreased bond strength for Concise, these values were
      well above the minimum values needed for successful bonding. Therefore, use of
      air-powder polishing on orthodontic bracket adhesive systems does not appear to
      be contraindicated.

PMID- 17233170
TI  - A national study of periodontal assessment by dental hygienists.
AB  - PURPOSE: Periodontal examination is one of the most frequently performed dental
      hygiene diagnostic services. This examination is the basis for effective dental
      hygiene treatment throughout long-term care. The purpose of this investigation
      was to examine how dental hygienists across the United States assess the
      periodontal status of three patient types: patients new to the practice,
      periodontally healthy recall patients, and periodontally unhealthy recall
      patients. METHODS: A two-stage cluster sampling method was used to select a
      random sample of dental hygienists from each of two states randomly selected from
      four regions of the United States. Questionnaires were mailed in 1989 to 2,618
      dental hygienists. Individual responses were scored according to criteria derived
      from dental literature for conducting seven components of a comprehensive
      periodontal examination. Results were calculated and analyzed for each state and
      region, and across regions for each patient type. RESULTS: Responses were
      received from 1,429 subjects, resulting in a 57.5% response rate of deliverable
      questionnaires. Overall mean scores (possible 0-7) across all regions were 3.68
      new patients, 3.22-healthy patients, and 2.67-unhealthy patients. Of the seven
      assessment components, three-gingival inflammation, furcation involvement, and
      radiographs-were performed according to the scoring criteria for all patient
      types by a majority of respondents. The criterion for periodontal pockets was met
      by a majority for new patients only. Three assessment component criteria were met
      by less than 40% of the sample for all patient types-attachment levels, mobility,
      and plaque control. Differences in the mean scores of certain states were found
      to be statistically significant. CONCLUSION: Specific dental hygiene standards
      are recommended for initial diagnostic and recall monitoring periodontal
      examinations. Additionally, dental hygiene administration and management of long
      term preventive and supportive periodontal therapy programs should assist in
      improving effectiveness of care and further delineate the profession of dental
      hygiene.

PMID- 17233171
TI  - A study of the dietary counseling practices among Oregon dental hygienists.
AB  - PURPOSE: The purpose of the study was to identify the dietary counseling
      practices of Oregon dental hygienists. Factors which affect the extent of dietary
      counseling were examined, including the dental hygienists' attitude, confidence,
      personal dietary practices, and perception of practice constraints. METHODS: A 25
      item survey was mailed in summer 1989 to a random sample of 300 Oregon licensed
      dental hygienists. Likert-scaled statements were used to measure the extent of
      dietary counseling activities and the factors which affect their extent. Multiple
      choice questions measured nutrition knowledge and quality of dietary counseling.
      Descriptive statistics were computed for each variable. Data were analyzed at the
      p<.05 significance level. Hypotheses testing included Pearson product-moment
      correlation, one-way analysis of variance (ANOVA), and chi-square. RESULTS: Of
      the 212 respondents (72% adjusted response rate), 52% reported providing dietary
      counseling. Ninety-six percent reported that they did not obtain dietary intake
      records and 82% did not evaluate their patients' diets for nutritional adequacy.
      A significant positive relationship (r=.19) was found between the hygienists'
      nutrition knowledge and quality of dietary counseling. Extent of counseling and
      the dental hygienist's confidence in nutrition knowledge and dietary counseling
      skills were found to be significantly related (r=-.31). A significant negative
      relationship (r= -.29) was found between extent of counseling and the dental
      hygienist's perception of practice constraints, most notably lack of time and
      cost-effectiveness. CONCLUSIONS: Dietary counseling is provided to a limited
      extent by dental hygienists in Oregon oral healthcare practices. Dental
      hygienists should provide this service based on patients' needs and, when
      necessary, refer patients to nutrition professionals. Further study could assess
      the nutrition and dietary counseling content and application in dental hygiene
      curricula.

PMID- 17233172
TI  - [Cooperation between Czech and Slovak paediatric surgeons].

PMID- 17233173
TI  - [Surgical complications following oesophageal replacement by stomach in
      childhood].
AB  - AIM: Assessment of surgical complications and options for their therapy following
      replacement of oesophagus by stomach. METHODOLOGY AND MATERIAL: A retrospective
      study of clinical and pathological data collected from 25 children, who underwent
      replacement procedures of their oesophagus by stomach during the 1992-2005
      period. 18 subjects were indicated for the procedure for oesophageal atresia with
      large stubs distance and 7 subjects were indicated for extensive oesophageal
      strictures following acid burns. RESULTS: The study group included 25 children
      whose mean age at the time of the procedure was 12.5 years (the age range 8 to
      13.3 years). Early postoperatively, a fistule in the oesophageal anastomosis
      region was confirmed in 7 subjects (28%), however, in all cases it healed
      successfully on conservative management. In five cases (20%), a stricture in the
      pyloric region developed and in 4 cases it was managed using balloon dilation.
      During the long-term follow up period, oesophageal anastomosis strictures were
      diagnosed in 9 children (36%). The problem was managed using repetitive balloon
      dilations. One child was operated for ileus with adhesions and in one child, a
      nutritional jejunostomy had to be re-conducted. One girl exited at home, a year
      following the procedure, due to respiratory arrest on aspiration. CONCLUSIONS:
      Transposition of the stomach is a suitable method of choice for oesophageal
      replacement in childhood, providing good quality of life for majority of
      patients. Early and late surgical complications correspond with a degree of
      seriousness of the disorder and require treatment and long term follow up to be
      conducted in a specialized clinic.

PMID- 17233174
TI  - [Morgagni diaphragmatic hernia in childhood].
AB  - The aim of this work was to retrospectively assess clinical and anatomical
      features of children with Morgagni congenital diaphragmatic hernias. The study
      group included 5 boys and 3 girls, aged between 5 months and 13 years, at the
      time of the diagnosis. Morgagni diaphragmatic hernia was diagnosed with non-acute
      symptoms in 8 children. A retrosternal defect of the diaphragm was left-sided in
      7 subjects and bilateral in 1 boy. A hernial sac was found in 6 children. In 3
      subjects, the hernial sac contained the liver, in 2 subjects the omentum, in 2
      subjects the transverse colon and small intestinal loops and in one child it
      contained the transverse colon with the omentum. In all cases, the diaphragmatic
      defect was closed using primary plasty. All subjects healed without
      complications. A differential diagnosis of congenital Morgagni hernia must be
      considered in children with unusual respiratory and gastrointestinal symptoms
      with abnormal x-ray findings on chest examination. A stricture of the congenital
      Morgagni diaphragmatic hernia is rare, and was not recorded in our group.

PMID- 17233175
TI  - [Laparoscopic surgery varicocele in the childhood and adolescent--our experience
      with 202 patients].
AB  - The aim of this work was to assess benefits and complications of laparoscopic
      procedures of varicocoelas in children and adolescents, conducted in our clinic.
      MATERIAL AND METHODOLOGY: From 2000 to 2004, 202 patients (198 with leftsided, 2
      with rightsided and 2 with bilateral varicocoelas) underwent laparoscopic
      procedures in our clinic. Patients with stage II and III varicocoelas were
      operated. The median age of the operated patients was 15 years (range 11-18
      years). The procedures saved arteries and lymphatics maximally. RESULTS: During a
      two-year follow up period, 8 patients (3.96%) relapsed, 21 patients (10.39 %)
      presented with hydroceolas. No testical hypotrophy was recorded in our patient
      group. Also, no peroperative complications were recorded during the laparoscopic
      procedures. The procedures lasted 20.4 min, on average, hospitalization lasted
      4.2 days, on average (range 4-6 days). CONCLUSION: Laparoscopic varicocolectomy,
      maximally saving arteries and lymphatics, proved a safe method. The rate of
      complications is similar to that of other treatment procedures of childhood
      varicocoelas. Rather long term effects considering a quality of hormonal
      production of testes and seminal counts, than postoperative complications rates,
      are the main parametres for choice of a treatment method.

PMID- 17233176
TI  - [Rates and histological characteristics of rectal polyps in childhood].
AB  - AIM OF STUDY: To determine a single centre incidence, rate of early and late
      complications and sequelae and histological characteristics of solitary
      rectosigmoideal polyps in children. METHODS: Retrospective analysis of hospital
      charts and histological characteristics of patients operated for rectosigmoideal
      polyps between January 1995 and December 2005. There were 23 children operated
      on, the study group consists of 20 patients (3 patients were excluded because of
      insufficient documentation). Demographics, symptomatology, season of first
      manifestation, localization, histology, postoperative complications and
      recurrence rate were evaluated. RESULTS: There were 7 boys and 13 girls in the
      study group (1:1.9), age at manifestation was 2-17 years (average 5.6 y.). The
      presenting symptom was bleeding in 14 pts, anal prolaps once and combination of
      both symptoms 5 times. The polyps were localized 3-15 cm from anocutaneous
      border, on the posterior intestinal wall. Histological examination showed a
      juvenile polyp in 15 (75%) patients, atypical juvenile polyp and inflammatory
      polyp in 2 patients each and lymphoid polyp in one case. One patient suffered
      from a mild bleeding postoperatively. No recurrence was noted. CONCLUSION: Polyps
      in children are rare, surgical removal of polyps is a relatively easy operation
      with minimum complications. Long term follow-up is not necessary. The seasonal
      occurrence of first symptoms predominantly in autumn and winter months (19 pts)
      has not been to our knowledge previously published.

PMID- 17233177
TI  - [Data collection and the Czech Republic Trauma Registry].
AB  - INTRODUCTION: A trauma registry is an integral part of any thorough
      traumatological care conception. The essential task of such a data collection is
      to provide complex information on conditions, treatment, outcomes and trauma
      treatment costs, considering a region or other registered part of, usually, a
      state entity. MATERIAL, METHODOLOGY: Registration of individual trauma
      characteristics throughout the state territory is a prerequisite for creating a
      data set, providing information for making valid conclusions applicable for all
      ranges of human activity. The trauma registry outputs are essential for traffic
      institutions, police, commercial inspection, commercial and health insurance
      companies, hospitals, etc. With respect to traffic problematics, the trauma
      registry plays a significant role in pointing out the most risk places in the
      region, in assessing the traffic type and use of protective tools. Furthermore,
      it facilitates exact aiming of preventive and corrective measures. CURRENT
      CONDITION: Current legislation does not require reporting data to the trauma
      database, insufficient data are provided by UZIS only. Our Clinic of Paediatric
      Surgery, Orthopaedics and Traumatology iniciated a model version of the Czech
      Republic National Trauma Registry. Our activities were approved by and supported
      by the Society of Traumatologic Surgery. It is a question of time, when
      sufficient pressure is exerted and the trauma registry becomes an integral part
      of the traumatological care in the Czech Republic.

PMID- 17233178
TI  - [Remodelling ability of the distal radius in fracture healing in childhood].
AB  - INTRODUCTION: Distal forearm fractures are among the commonest skeletal injuries
      in childhood. The aim of this work is to analyze factors determining remodelling
      abilities of the distal radial metaphysis in dislocated fractures, considering a
      requirement for eventual non-operative repositioning. MATERIAL AND METHODOLOGY:
      The primary patient group included a group of patients treated in 2004 for distal
      radial metaphysis fractures, left to heal in a dislocated position. The angle of
      dislocation ranged from 8 to 30 degrees. All patients underwent a follow up x-ray
      examination 2, or more, years later and a clinical examination of the wrist joint
      range of motion. The extent of remodellation was studied, considering duration of
      the healing process, patient's age and the fracture line distance from the growth
      plate. RESULTS: The results show that in the majority of the patients included in
      the study, complete remodellation of the radius nearly to its anatomical position
      (86%) occurred. The results were significantly better in the patient group aged 0
      12 years. Furthermore, significantly less residual dislocations were recorded
      within 20 mm from the growth plate. Restriction of the wrist joint range of
      motion resulting from residual dislocation was not recorded. CONCLUSION: Based on
      the results, conservative treatment of the condition, especially in cases of
      multiple injuries or of a polytrauma, is recommended. Also, in cases of
      deterioration of the positioning or of redislocation after repositioning,
      repositioning need not be repeated in patients below 12 year of age.

PMID- 17233179
TI  - [Manual and robotic laparoscopic liver resection. Two case-reviews].
AB  - INTRODUCTION: Laparoscopic resection of the liver, compared to other laparoscopic
      procedures of the abdominal cavity, have become used in a clinical practice only
      in recent years. No literature data on robotic liver resections are available.
      METHODS: The authors completed 2 laparoscopic resections of the liver. The first
      case included a 61-year old male indicated for the procedure with a low
      differenciated hepatocellular carcinoma lesion in SII and SIII segments,
      measuring 6 cm in a diameter, in a Child A cirrhotic remodellation terrain. In
      line RFA-assisted and HandPort-assisted manual laparoscopic left-sided lobectomy
      was completed. Histological findings confirmed the diagnosis and the R0
      resection. Robotic laparoscopic resection of the focal nodular hyperplasia (FNH)
      lesion, growing from SII and SIII segments and measuring 7x7x5 cm was completed
      in the other case of a 29-year old female patient. RESULTS AND CONCLUSION: Both
      patients healed without complications, the hospitalization lasted 8 and 7 days,
      respectively. HandPort-assisted manual laparoscopic resections of the left liver
      lobe appears a safe method. The patient may benefit from a smaller entrance into
      the abdominal cavity, compared with open abdominal procedures. Experience in
      liver and laparoscopic surgery is a prerequisite, which is also supported by
      literature data. A pilot study must be conducted in order to assess benefits of
      robotic laparoscopic liver resections.

PMID- 17233180
TI  - [Complications of the Longo Procedure--rectal occlusion].
AB  - Longo Procedures on hemorrhoids are widely used and standard surgical procedures
      used in many surgical clinics. Extensive studies, describing benefits and
      possible complications of the method in a detail, are published in Czech and
      foreign literature. A wide range of complication rates (5-20%) is reported by
      individual clinics, however, the rates decrease proportionally to the surgeon's
      growing experience and mastering of the method. The complications reported are
      mostly non-serious, bleeding from stapled sutures is one of the commonest ones.
      However, more serious complications including suture dehiscence or rectovaginal
      fistules, are less common. Our case-review presents an unusual complication after
      the procedure, a blind closure of the rectum with a circular PPH stapler. No
      similar complication has been found in the available literature.

PMID- 17233181
TI  - [Preoperative radiotherapy in hypoxia in the complex treatment of the rectal
      carcinoma--complications].
AB  - INTRODUCTION: Preoperative radiotherapy is considered to be the standard approach
      in the treatment of the rectal carcinoma. Acute hypoxia decreases partial
      pressure of oxygen in healthy tissues immediately, but in the tumor after 30 min
      of duration. There is a higher radioresistance of healthy tissues in this
      interval because of lower oxygenation compared with normooxic status and the
      tumor is still relatively good oxygenated. This fact theoretically enables higher
      doses of radiotherapy and lower adverse effects. The aim of this study was to
      evaluate short and long term complications after preoperative radiotherapy of
      rectal carcinoma in hypoxia. PATIENTS AND METHODS: Between April 1991 and October
      2000, 127 patients with the rectal carcinoma were treated preoperatively with
      locoregional accelerated hypofractionated radiotherapy in hypoxic conditions in
      Masaryk Memorial Cancer Institute. The dosis was up to 8 x 4 Gy. Acute hypoxia
      was induced during irradiation by ventilation of a hypoxic gas mixture containing
      7.8-8.0% oxygen for totally 7-8 min. Operation was performed till 24 hours.
      RESULTS: There was no complication concerning with breathing of hypoxic gas
      mixture. A 30 day postoperative mortality was 0.8%. A 30 day postoperative
      morbidity was 31.7%. An anastomotic leakage occurred in 6.5%. Chronic
      gastrointestinal disorders occurred in 16.1% patients. CONCLUSION: Preoperative
      irradiation in hypoxic conditions is safe and efficient procedure. It permits
      safe administration of doses higher than those tolerated by normooxic conditions.
      Type and frequency of complications are comparable with other preoperative
      regimens.

PMID- 17233182
TI  - [Long-term experience with MESA, TESE techniques in the University Hospital (FN)
      in Brno].
AB  - Authors evaluated the experience of application MESA, TESE and ICSI techniques
      during 9 years long cooperation between Department of Urology University Hospital
      Brno and Institulions of reproductive Medicine University Hospital Brno. 104
      surgical procedures were performed during this time period and as result 24
      children were born.

PMID- 17233183
TI  - [Arthroscopic management of traumatic luxation of the patella].
AB  - AIM: The authors present a restrospective assessment of acute traumatic patellar
      luxation. MATERIAL: From 1999 to 2003, the authors treated 57 patients with acute
      traumatic patellar luxations, including 36 females and 21 males, the age range
      was 16-40 years. In cases of marked lateralization of the patella, the injured
      medial retinaculum was sutured under arthroscopic control. Furthermore, should
      the lateralization persist, lateral release of the patella was conducted. Early
      patellar cartillage injuries were detected in 34 subjects (59%), injuries of the
      lateral femoral condyle in 19 subjects (33 %). Patellar chondromalacia, grade 1-2
      was diagnosed in 16 subjects. Free cartillagenous particles within the joint were
      detected in 18 subjects. Reconstruction of the cartillage was conducted in
      extensive injuries in 13 subjects. RESULTS: The subjects were assessed 1-4 years
      after the injuries and surgery. In one case (2%), a relaps of the patellar
      luxation, due to a new contact sport injury (a direct impact), was recorded.
      Assessment results, using the Lysholm score, were defined as follows: 93%
      excellent and good, 7% fair. CONCLUSION: Sparing surgical techniques, followed by
      appropriate rehabilitation care, may optimalize the healing process of the
      injured tissue and prevent relapses of patellar luxations, as well as further
      wearing of femoropatellar cartillages.

PMID- 17233184
TI  - Integrated, collaborative disaster response networks.

PMID- 17233185
TI  - MALT lymphomas--a closer look in the genomics era.

PMID- 17233186
TI  - Drug-drug interactions and statin therapy.

PMID- 17233187
TI  - Angiotensin-converting enzyme (ACE) inhibitor-induced acute pancreatitis: in
      search of the evidence.

PMID- 17233188
TI  - Hurricanes Katrina and Rita: evacuee healthcare efforts remote from hurricane
      affected areas.
AB  - Hurricanes Katrina and Rita produced the largest evacuation due to a natural
      disaster in United States history. Many people were evacuated or rescued from New
      Orleans and the Gulf Coast, resulting in a need for mass disaster shelters and
      medical care for months following the storms. The shelter healthcare system that
      was successfully developed in the Shreveport-Bossier City, Louisiana area was
      accomplished with little support from customary sources. This report is written
      after much discussion and introspection of community leaders involved "on the
      ground," who organized and provided medical services to evacuees of south
      Louisiana. Its purpose is to compile "lessons learned" in preparation for the
      next disaster recovery effort that might affect this or any other region of our
      country.

PMID- 17233189
TI  - Facing the malpractice crisis: academic physicians' willingness to accept quick
      fix solutions.
AB  - BACKGROUND: We sought to determine the willingness of academic physicians to
      accept strategies to contain institutional malpractice costs. METHODS: We
      surveyed all 270 Department of Medicine physicians at a large academic center.
      Respondents were asked about their knowledge regarding malpractice premiums,
      willingness to reduce patient-care activities and accept decreases in
      compensation. RESULTS: The response rate was 80%. Respondents estimated the
      annual increase in malpractice premiums from 2004 to 2005 to be 29%. The true
      increase was 28% (P = 0.55). Almost all opposed eliminating patient care (95%) or
      providing patient care every other year at double effort and withdrawing from
      patient care on alternate years (97%). Seventy percent would limit their clinical
      procedures. Most physicians opposed salary reduction (97%) or decreases in fringe
      benefits (99%). CONCLUSIONS: Few academic physicians are willing to limit patient
      care or accept decreases in compensation to recoup institutional malpractice
      costs.

PMID- 17233190
TI  - Chart documentation of informed consent for operative vaginal delivery: is it
      adequate?
AB  - OBJECTIVES: To determine the documentation frequency of informed consent for
      women undergoing a trial of nonemergent instrumental delivery. STUDY DESIGN: A
      retrospective chart review of instrumented vaginal deliveries from 1992 to 2005
      was performed. Cases were identified from a Labor and Delivery database and
      hospital records were reviewed for documentation of associated risks, general
      consent for the procedure, indication, and option of cesarean delivery (CD).
      RESULTS: Three hundred forty six charts were reviewed: 246 were excluded for an
      emergency delivery (19%), misclassification (25%), or lost notes (27%). In the
      remaining 100 cases, 61% had a general consent for instrumented vaginal delivery.
      Documentation of any maternal or neonatal risks was found in 3% and 0%,
      respectively. The option of a cesarean delivery was documented in 22% of the
      cases. When comparing 5-year time intervals before and after 2000, there was no
      increased frequency in documentation of maternal or neonatal risks. CONCLUSIONS:
      Documentation of informed consent for instrumented vaginal delivery is
      inconsistent and should be improved.

PMID- 17233191
TI  - Update in the approach to and management of heart failure.
AB  - Heart failure (HF) is a prevalent and morbid chronic disease that patients
      experience in stages. Progression through the stages of HF can be slowed with
      optimal medical therapy. Although HF remains a clinical diagnosis made at the
      bedside, measurement of serum brain natriuretic peptide (BNP) can help in the
      diagnosis when there is uncertainty. The initial workup for patients with newly
      diagnosed HF is directed at identifying the underlying cause of left ventricular
      dysfunction. An assessment of hemodynamic status, determined by a careful
      physical examination, can be used to direct therapy. Angiotensin-converting
      enzyme inhibitors (ACEIs) and beta blockers remain the two most important
      therapies for patients with chronic HF. Aldosterone antagonists improve mortality
      but require close monitoring for severe hyperkalemia. Angiotensin-receptor
      blockers (ARBs) are excellent alternatives to ACEIs for ACEI-intolerant patients.
      Digoxin, a second line agent in HF, improves symptoms without mortality benefit.
      Successful management of HF requires aggressive management of comorbid conditions
      and careful follow up to slow disease progression, optimize functional status,
      and improve longevity.

PMID- 17233192
TI  - Advances in the endoscopic management of patients with pancreatic and biliary
      malignancies.
AB  - Major advances in endoscopic techniques to diagnose and manage pancreatic biliary
      diseases have fundamentally changed the approach to these difficult clinical
      challenges. The diagnosis of benign and malignant pancreatic-biliary diseases is
      much more readily obtained through a combination of cross-sectional imaging and
      endoscopic procedures. Endoscopic retrograde cholangiopancreatography (ERCP) and
      endoscopic ultrasound (EUS) are the most important endoscopic tools for imaging
      and accessing the pancreatic biliary system. The review summarizes the major
      imaging methods for providing a diagnosis of bile duct malignancy, including
      ERCP, transhepatic cholangiography (THC), and magnetic resonance
      cholangiopancreatography (MRCP). High quality image examples of
      cholangiocarcinoma are provided. EUS has provided a new imaging modality for the
      detection of pancreatic and biliary malignancy. EUS is particularly sensitive for
      the detection of early pancreatic malignancy. Furthermore, EUS excels at the
      guidance of fine needle aspiration of pancreatic lesions. Diagnostic tissue
      acquisition for cholangiocarcinoma remains an important challenge. The endoscopic
      therapy for pancreatic-biliary malignancy involves the use of stenting which
      relieves the biliary obstruction commonly seen in these patients.

PMID- 17233193
TI  - Patent foramen ovale: assessment, clinical significance and therapeutic options.
AB  - Foramen ovale plays an important function in the fetus but is of no physiologic
      significance after birth and closes in most individuals. In about one fourth of
      the population, however, foramen ovale remains open for life and has been
      associated with cerebrovascular accidents, especially in younger patients,
      presumably through paradoxical embolism. Patent foramen ovale (PFO) has also been
      associated with hypoxia, migraine headaches and neurologic findings of
      decompression illness in scuba divers. Availability of transesophageal
      echocardiography and its frequent use in the management of patients with stroke
      has lead to frequent detection of PFO. In addition, the recent development of
      devices and techniques for percutaneous closure of PFO has resulted in widespread
      enthusiasm for such interventions, even when a clear etiologic role for PFO may
      not be established. In the United States, the Federal Drug Administration (FDA)
      has approved two such devices through compassionate investigational device
      exemption without adequate data from large randomized clinical studies. Other
      such devices are undergoing evaluation in clinical trials. Expert opinions have
      been helpful for clinical decision making in management of patients with PFO
      associated with stroke, hypoxia, decompression sickness and migraine headaches.

PMID- 17233194
TI  - Pharmacologic management of chronic insomnia.
AB  - Chronic insomnia is a common disorder that is under recognized, under diagnosed
      and under treated. Initial assessment should focus on identifying and treating,
      if present, any secondary causes of insomnia. Primary insomnia can be treated
      with behavioral and/or pharmacological therapy. A thorough sleep history can
      identify the type of insomnia present, its severity, and can consequently guide
      therapy. Behavioral therapy has been shown to be equivalent to or superior to
      pharmacologic therapy, at least in some patients. It is a reasonable initial
      approach, although there are barriers to its use. There are several pharmacologic
      agents available, some of which are more effective at reducing time to fall
      asleep and others for maintaining sleep. There is some evidence to indicate that
      combining the approaches may impair outcomes. There is little data on the long
      term use of pharmacologic agents.

PMID- 17233195
TI  - Primary mucosa-associated lymphoid tissue (MALT) lymphoma occurring in the
      rectum: a case report and review of the literature.
AB  - The primary extranodal B-cell lymphoma of mucosa-associated lymphoid tissue
      (MALT) is a distinct clinical pathologic entity that develops in diverse anatomic
      locations such as the stomach, salivary gland, thyroid, lung, and breast;
      however, colorectal involvement is rare. To the best of our knowledge, only 30
      cases of primary rectal MALT lymphoma have been published in the English language
      literature, mostly from Japan. A single case has been reported from the US before
      this report. The most common symptoms ranged from asymptomatic to occult or gross
      gastrointestinal bleeding. Simultaneous involvement of the cecum or colon was
      seen in 20% of the patients. Ninety percent of the patients were classified as
      low grade, Stage 1 at the time of diagnosis. Polypoid lesions were 10-fold more
      common than ulcerative lesions. Seven patients were reported to have H pylori in
      the stomach. The majority of the patients underwent surgical or endoscopic
      resection as a cure; however, controversy exists with regards to antibiotic
      treatment or observation alone because of unknown etiopathogenesis. Infection
      with microorganisms other than H pylori has been postulated in the development of
      rectal MALT lymphoma; however, this hypothesis remains unproven. The overall
      prognosis of rectal MALT lymphoma appears favorable; however, long-term follow-up
      data is lacking. Therefore, periodic clinical monitoring should be done in these
      patients.

PMID- 17233196
TI  - Lipid lowering inefficacy of high-dose statin therapy due to concurrent use of
      phenytoin.
AB  - HMG-CoA reductase inhibitors ("statins") are the most commonly prescribed lipid
      lowering agents. Most of the statins are metabolized by the CYP450 cytochrome
      system. A number of medications either induce or inhibit this system which leads
      to changes in the bioavailability of the statins and the potential for either an
      increase in adverse effects or reduction in efficacy. Phenytoin induces the
      CYP3A4 isoform of the CYP450 system and can reduce the bioavailability, and thus
      the efficacy of the statins metabolized by this enzyme, including atorvastatin
      and lovastatin. A case of a patient on multiple lipid-lowering medications,
      including high-dose atorvastatin whose LDL cholesterol improved significantly
      after discontinuation of phenytoin is presented, and a review of the literature
      for similar cases is discussed.

PMID- 17233197
TI  - Recurrent acute pancreatitis probably secondary to lisinopril.
AB  - OBJECTIVES: Few data exist about the incidence of drug-induced acute pancreatitis
      in the general population. Although angiotensin-converting enzymes are generally
      well tolerated, acute pancreatitis has been reported in a few subjects treated
      with captopril, enalapril, and lisinopril. However, to our knowledge, there is no
      published data regarding recurrent pancreatitis secondary to lisinopril. Herein,
      we report the case of a 54-year-old man who developed recurrent acute
      pancreatitis after starting lisinopril. CLINICAL PRESENTATION: A 54-year-old man
      with a longstanding history of hypertension, treated with lisinopril 10 mg once
      daily, presented with acute pancreatitis. Other causes of the disease were ruled
      out. After cessation of lisinopril, his condition improved and his amylase level
      decreased. This was his third episode of acute pancreatitis since lisinopril had
      been started in 2002. After discontinuing lisinopril and beginning treatment with
      amlodipine 10 mg/d, the patient was well at follow-up examination and has not had
      another episode of pancreatitis during the subsequent 7 months. CONCLUSION: This
      case report demonstrates additional evidence of acute pancreatitis associated
      with an ACE inhibitor.

PMID- 17233198
TI  - Hypertrophic cardiomyopathy and symptomatic conduction system disease in cardiac
      amyloidosis.
AB  - Cardiac involvement is the most important prognostic factor in primary
      amyloidosis (AL). The clinical presentation of amyloid cardiomyopathy is varied
      and may manifest as heart failure, brady or tachyarrhythmias, syncope, angina and
      rarely with features of hypertrophic cardiomyopathy and advanced symptomatic
      conduction system disease. The management of amyloid cardiomyopathy has always
      been a dilemma, as most of the drugs used in congestive heart failure are
      contraindicated. This report describes a 70-year-old woman who presented with
      syncope, severe diastolic heart failure, features of hypertrophic cardiomyopathy
      and severe symptomatic conduction system disease requiring a pacemaker.
      Amyloidosis was diagnosed on endomyocardial biopsy after abdominal fat aspirate
      was negative for amyloid. The patient eventually expired due to end-stage
      congestive heart failure.

PMID- 17233199
TI  - A case of skin hypopigmentation secondary to a corticosteroid injection.
AB  - A 47-year-old African-American male presented complaining of Achilles tendon
      pain. The patient was treated for three weeks with a nonsteroidal anti
      inflammatory agent with minimal pain relief. The tendon was subsequently injected
      with triamcinolone acetonide and five months later, the patient presented with an
      area of hypopigmentation around the injection site. The patient was diagnosed
      with hypopigmentation secondary to the steroid injection.

PMID- 17233200
TI  - Metastatic malignant pleural mesothelioma to the breast.
AB  - A 51-year-old woman suffered from dyspnea for several days before she came to an
      outside clinic for help. Pleura biopsy was performed and the histologic diagnosis
      was malignant mesothelioma. Sixteen months later, a palpable left breast lump was
      noted. Physical examination revealed a firm mass in the breast, measuring about 4
      x 3.5 cm in size. Breast sonography showed a hypoechoic mass about 3 x 2 x 1.5 cm
      in size with irregular border in the middle part of the left breast. A mammogram
      revealed a speculated mass. Chest computed tomography was also performed, which
      revealed a large pleural mesothelioma and an irregular breast lesion. Incisional
      biopsy of the left breast lump was performed and histologic examination revealed
      an infiltrative growth of neoplastic polygonal cells bearing hyperchromatic and
      pleomorphic nuclei and a small amount of pale, pinkish cytoplasm. Further
      immunohistochemical study was performed and the tumor cells were positive for low
      and high molecular weight cytokeratin, thrombomodulin and focally positive for
      CEA. The final histologic diagnosis was metastatic malignant mesothelioma.

PMID- 17233201
TI  - Invasive aspergillosis in immunocompetent patients.

PMID- 17233202
TI  - Hepatotoxicity after low-dose cyclophosphamide therapy.

PMID- 17233203
TI  - Edematous obstructive sleep apnea patients have low normal serum albumin levels.

PMID- 17233204
TI  - Closure of round cutaneous postoperative wounds with the purse string suture.

PMID- 17233205
TI  - An adolescent with chest pain.

PMID- 17233206
TI  - Payment as motivator in Iranian medical students' attitudes toward research.

PMID- 17233207
TI  - Post abortion survivor syndrome (PASS): signs and symptoms.

PMID- 17233208
TI  - Percutaneous computed tomography-guided needle aspiration drainage of spinal
      epidural abscess.

PMID- 17233209
TI  - Baseline electrocardiographic changes as determinants in the prognosis of
      cerebrovascular accidents.

PMID- 17233210
TI  - Prolonged livestock exposure and elevated serum IgE associated with pulmonary
      fibrosis.

PMID- 17233211
TI  - Patient's page. Spirituality and health: what your doctor needs to know.

PMID- 17233212
TI  - A historical look at hypertension: celebrating 100 years with the Southern
      Medical Association.

PMID- 17233213
TI  - To condone or to condemn? On the ethics of stem cell research.

PMID- 17233214
TI  - The sound of science: the power to bless or to burn.

PMID- 17233215
TI  - Promethean medicine: spirituality, stem cells, and cloning.
AB  - Every ethos implies a mythos. That is, every ethical system depends upon some
      fundamental story disclosing its assumptions about human nature, freedom, good
      and evil, and the workings of the universe. A romanticized version of the myth of
      Prometheus, who stole fire from the gods and was punished by being chained to a
      rock and having his liver plucked out by vultures, seems to under-gird much of
      contemporary healthcare. Christianity offers a different view--one in which the
      universe is not a zero sum game and human beings do not need to steal fire
      because God has already freely given them all the fire they need in Christ and in
      his spirit. A critical virtue for physicians, taught by Christianity, is
      sagacious engagement--the ability to engage the world practically, discerning
      what can and should be changed and what should be accepted as unchangeable and
      given. The illusory quest for immortality through the practice of regenerative
      medicine using stem cells is a gross violation of that virtue.

PMID- 17233216
TI  - Internal morality of motherhood and integrity of physicians in the era of
      assisted reproductive technologies (ARTs).

PMID- 17233217
TI  - Cloning: US and global perspectives.

PMID- 17233218
TI  - Human embryonic stem cells: a justification for their use in medical
      therapeutics.

PMID- 17233219
TI  - Current status of research using human embryonic stem cells.

PMID- 17233220
TI  - "No" to embryonic stem cells.

PMID- 17233221
TI  - "Yes" to adult stem cells.

PMID- 17233222
TI  - Integrative research: the approach at the Harvard Stem Cell Institute.

PMID- 17233224
TI  - Eye on religion: Buddhism and medicine.

PMID- 17233223
TI  - Eye on religion: understanding the cultural/religious melange in treating
      Japanese patients.

PMID- 17233225
TI  - Eye on religion: by the brush and by the sword: Daoist perspectives on the body,
      illness, and healing.

PMID- 17233226
TI  - Anatomy of the salivary glands.
AB  - This article describes the anatomy of the salivary glands highlighting those
      anatomical features that are relevant to the radiologist. Magnetic resonance
      images with super-imposed line illustrations have been used to aid the
      understanding of the anatomy of this region.

PMID- 17233227
TI  - Inflammatory conditions of the salivary glands.
AB  - Inflammatory conditions are the most common pathology to affect the salivary
      glands, of which sialolithiasis is the most frequent etiology. This article
      reviews the role of all imaging modalities in the management of inflammatory
      salivary disease. The technique for performing salivary gland ultrasound is
      described with some common pitfalls. The typical features of a comprehensive
      range of pathology including obstructive and infective sialadenitis, Sjogren's
      syndrome, sarcoidosis, HIV sialopathy, and their complications are described.

PMID- 17233228
TI  - Tumors of the salivary glands.
AB  - This article reviews the role of imaging in the management of tumors of the
      salivary glands, discussing tumor localization, extent, and, where possible,
      characterization. The relative benefits of the different modalities and the
      typical features of benign and malignant lesions are discussed for each modality.
      Characteristic appearances of specific tumors are highlighted.

PMID- 17233229
TI  - Interventional sialography and minimally invasive techniques in benign salivary
      gland obstruction.
AB  - Salivary gland obstruction is the commonest complaint affecting this organ and is
      usually due to the development of salivary calculi, ductal strictures, or both.
      Imaging has a role in the diagnosis of the cause, extent, and effects of
      obstruction. In recent years, the role of radiology has evolved; techniques, such
      as salivary stone lithotripsy, and salivary stone extraction and balloon
      ductoplasty are carried out under imaging guidance. This article reviews the
      current status of minimally invasive salivary interventions.

PMID- 17233230
TI  - Imaging of the lacrimal gland.
AB  - The lacrimal gland is situated superolateral to the eye and produces tears that
      moisten, lubricate, and protect the delicate corneal and conjunctival epithelium.
      Anatomically related to the orbit but embryologically and functionally more
      closely related to the salivary glands, radiological imaging has proven
      invaluable in delineation and differentiation of the unique range of pathological
      processes affecting the lacrimal gland. This article details traditional and new
      imaging techniques used in investigating such pathology and discusses the imaging
      findings and patterns of spread characteristic of various neoplastic,
      inflammatory, and structural processes ranging from benign adenomas,
      adenocarcinomas, and lymphomas to sarcoidosis, Mickulicz's syndrome,
      histiocytosis, and benign dacrocysts.

PMID- 17233231
TI  - Psychologically healthy workplaces.

PMID- 17233233
TI  - A stage-targeted physical activity intervention among a predominantly African
      American low-income primary care population.
AB  - PURPOSE: To examine the efficacy of a stage-targeted physical activity
      intervention among low-income African-Americans. METHODS: 207 participants were
      randomly assigned to groups and administered baseline measures. Intervention
      participants were mailed stage-targeted physical activity information, whereas
      control participants received low-sodium diet brochures. Measures were
      readministered by phone 1 and 6 months later, with response rates of 69% and 46%,
      respectively. RESULTS: 69% of participants were African-American and 64% had a
      monthly household income of < $1000. A doubly-multivariate analysis of variance
      indicated that intervention participants reported more physical activity than
      control participants at 1 month (F(1, 204) = 4.03, p < .05). Unlike control
      participants, intervention participants reported significant stage progression at
      1 month, according to a McNemar chi2 test. Gains attenuated by 6 months.
      CONCLUSIONS: The current study supports the use of this intervention among low
      income African-Americans. Limitations include use of self-report measures and
      small sample size.

PMID- 17233232
TI  - Successfully improving physical activity behavior after rehabilitation.
AB  - PURPOSE: To determine the effects of the physical activity promotion programs
      Rehabilitation & Sports (R&S) and Active after Rehabilitation (AaR) on sport and
      daily physical activity 1 year after in- or outpatient rehabilitation. DESIGN:
      Subjects in intervention rehabilitation centers were randomized into a group
      receiving R&S only (n = 315) and a group receiving R&S and AaR (n = 284).
      Subjects in six control centers (n = 603) received usual care. SETTING: Ten Dutch
      rehabilitation centers. SUBJECTS: Subjects consisted of 1202 rehabilitation
      patients. Most frequent diagnoses were stroke, neurological disorders, and back
      disorders. INTERVENTION: Both the sport stimulation program (R&S) and the daily
      physical activity promotion program (AaR) consisted of personalized tailored
      counseling. MEASURES: Two sport outcomes and two daily physical activity outcomes
      were assessed with questionnaires at baseline and 1 year after rehabilitation.
      ANALYSIS: Multilevel analyses comparing both intervention groups to the control
      group. RESULTS: The R&S program showed no significant effects. Intention-to-treat
      analyses in the R&S + AaR group showed borderline significant improvements in one
      sport (odds ratio [OR] = 1.66, p = .02) and both physical activity outcomes (OR =
      1.68, p = .01 and regression coefficient = 10.78, p = .05). On-treatment analyses
      in the R&S + AaR group showed similar but stronger effects. CONCLUSIONS: The
      combination of the R&S and AaR programs improved physical activity behavior and
      sport participation 1 year after in- or outpatient rehabilitation. The R&S
      program alone did not have any effects.

PMID- 17233234
TI  - Evaluation of United States Department of Agriculture-sponsored consumer
      materials addressing food security.
AB  - PURPOSE: Food insecurity in the United States is a major public health issue. The
      main objective of this study was to evaluate the availability and quality of
      printed materials addressing food security targeted to special populations by the
      United States Department of Agriculture (USDA). DESIGN: Nutrition education
      resources addressing food security available from USDA websites were selected for
      analysis. SETTING: Not applicable. PARTICIPANTS: The review team consisted of
      project staff (n = 6), two of who were fluent in Spanish. METHOD: Selection
      criteria were established to identify the food-security materials, and a group of
      reviewers assessed the quality of each publication both quantitatively and
      qualitatively. A consensus meeting among the reviewers was held to make final
      determinations of the quality of the materials. The quantitative data analysis
      consisted of basic descriptive statistics. RESULTS: Among the 27 materials
      initially identified, 20 were either irrelevant or of low relevance to food
      security. Moreover, very few of them were intended for minority populations. The
      quality of most of the materials ranged from "average" to "good." Some of the
      major weaknesses include readability level, lack of cultural relevance, and
      inadequate coverage of food insecurity. CONCLUSION: Very few materials on food
      insecurity are of high quality. In the development of such materials, emphasis
      should be given to the readability level, content, and cultural relevance.

PMID- 17233235
TI  - Work-to-family spillover and fruit and vegetable consumption among construction
      laborers.
AB  - PURPOSE: Spillover is the effect of one role on another as working adults attempt
      to integrate demands from work and family. We conducted a survey to understand
      how worker, job, and family characteristics were related to negative work-to
      family spillover and how spillover was related to fruit and vegetable consumption
      to inform intervention design. DESIGN: A combined mail and telephone survey.
      SETTING: A national random sample in the United States. SUBJECTS: 1108 (44%
      response) unionized construction laborers. MEASURES: Personal characteristics,
      job factors, family factors, work-to-family spillover, and fruit and vegetable
      consumption. ANALYSIS: Multivariable logistic and least-squares regression.
      RESULTS: A range of 20% to 50% of respondents reported negative work-to-family
      spillover, agreeing that work demands, time, fatigue, and stress interfered with
      family meals or food choices. Higher spillover was associated with job factors,
      being of white race/ethnicity, and having children at home. Lower fruit and
      vegetable consumption was associated with higher work-to-family spillover (p =
      .002), being of white race or ethnicity (p < .0001), and working the graveyard or
      day shift (p = .02). CONCLUSION: Negative experience of work-to-family spillover
      may link employment to fruit and vegetable consumption and thus to worker health.
      Understanding the contribution of spillover to fruit and vegetable consumption
      aids understanding of how work experience affects health.

PMID- 17233236
TI  - Baseline characteristics and recruitment strategies in a randomized clinical
      trial of African-American light smokers.
AB  - PURPOSE: This study describes the design, recruitment, and baseline data of the
      first smoking-cessation clinical trial for African-American light smokers, Kick
      It at Swope II (KIS-II). DESIGN: KIS-II was a randomized trial testing the
      efficacy of nicotine gum (vs. placebo gum) in combination with counseling
      (motivational interviewing or health education). SETTING: This study was
      conducted at an urban community-based clinic serving predominantly lower-income
      African-Americans. SUBJECTS: African-Americans who smoked 1 to 10 cigarettes per
      day were eligible. Of 1933 individuals screened, 1012 (52%) were eligible and 755
      (75%) were enrolled in the study. MEASURES: Baseline assessment included smoking
      history and psychometric measures. ANALYSIS: The majority of participants were
      women (67%) with a mean age of 45.1 years (SD = 10.7). Participants smoked on
      average 7.6 cigarettes (SD = 3.21) per day, had a mean exhaled carbon monoxide
      level of 13.9 ppm (SD = 8.9) and a mean serum cotinine level of 244.2 ng/mL (SD =
      154.4), and reported high levels of motivation and confidence to quit smoking.
      CONCLUSION: African-American light smokers were motivated to stop smoking and to
      enroll in a smoking-cessation program. Characteristics of our sample suggest
      African-American light smokers are an appropriate group for inclusion in smoking
      cessation interventions.

PMID- 17233237
TI  - Prenatal smoking cessation among Black and White women in Eastern North Carolina.
AB  - PURPOSE: Limited information is available about Black:White disparities in
      prenatal smoking cessation, and the results of prior research are inconsistent.
      We analyzed smoking cessation and factors associated with cessation (attitudes,
      environment, and nicotine addiction) in a sample of pregnant Black and White
      women. METHODS: Women were interviewed at the first prenatal visit at two
      hospital-based clinics. RESULTS: Among former and current smokers, there were no
      significant differences in the percentage of former smokers between Black (46.8%)
      and White (43.3%) pregnant women, or in the percentage of "spontaneous quitters"
      (i.e., those who quit after learning that they were pregnant) for Blacks (36%)
      and Whites (28%). Both Black and White spontaneous quitters had evidence of
      occasional relapses to smoking. For Black and White women, smoking more than a
      pack a day prior to pregnancy was associated with smoking during pregnancy.
      DISCUSSION: Among current and former smokers, spontaneous cessation was about the
      same for Black and White women, and about two thirds of women who were smokers
      when they learned of the pregnancy continued to smoke during pregnancy. Nicotine
      addiction contributed to continued smoking.

PMID- 17233238
TI  - Workers' perceptions about worksite policies and environments and their
      association with leisure-time physical activity.
AB  - PURPOSE: To estimate the employed population's exposure to perceived worksite
      policies and environments hypothesized to promote physical activity and to
      determine their relationship to leisure-time physical activity. DESIGN: Cross
      sectional, random-digit-dial telephone survey. SETTING: Community. SUBJECTS:
      Employed adults (n = 987) in six North Carolina counties. MEASURES: Outcomes
      included any leisure-time physical activity, recommended physical activity, and
      work-break physical activity. Perceived worksite policies and environments
      included on-site fitness facility at work, safe place to walk outside work, paid
      time for activity, subsidized health-club membership, and flexible work schedule.
      ANALYSIS: Descriptive statistics were used to describe the study population and
      exposure to perceived worksite policies and environments. Multivariable logistic
      regression was used to evaluate relationships between perceived worksite policies
      and environments and physical activity, controlling for age, race, sex,
      educational status, disability, and general health status. RESULTS: Various
      supportive worksite policies and environments were reported by 15% to 56% of
      employed participants. Associations between perceived worksite policies and
      environments and physical activity were strongest for having paid time for non
      work-related physical activity, an on-site fitness facility at work, and
      subsidies for health clubs. Recommended activity was not associated with
      perceived worksite policies and environments. CONCLUSION: Worksite policies and
      environments are promising factors for future study in physical activity
      promotion. Studies should evaluate these relationships in other populations and
      explore measurement error in self-reported worksite policies and environments.

PMID- 17233239
TI  - Associations of children's perceived neighborhood environments with walking and
      physical activity.
AB  - PURPOSE: To examine associations between children's perceptions of the
      neighborhood environment and walking and physical activity. DESIGN: Cross
      sectional study of a school-based sample. SETTING: Elementary schools in
      Melbourne, Australia. SUBJECTS: 280 children aged 10 years (response rate 78%).
      MEASURES: A self-report survey assessed children's perceptions of the
      neighborhood physical and social environments and their weekly walking frequency.
      Physical activity was also objectively measured using accelerometers. RESULTS:
      Multiple linear regression analyses showed a positive association between walking
      frequency and the number of accessible destinations in the neighborhood among
      boys; having a neighborhood that was easy to walk/cycle around and perceiving
      lots of graffiti were positively associated with walking frequency among girls.
      Perceiving lots of litter and rubbish was positively associated with boys'
      overall physical activity, but no environmental variables were associated with
      girls' overall physical activity. CONCLUSION: Several different environmental
      factors were associated with walking and physical activity. Perceptions of the
      neighborhood environment were more strongly associated with girls' walking than
      with objectively-measured physical activity. Future studies should confirm these
      findings using objective measures and prospective study designs.

PMID- 17233240
TI  - Well-being: new paradigms of wellness--inspiring positive health outcomes and
      renewing hope.
AB  - A case for the inclusion of well-being as a direct and explicit objective in our
      worksite health promotion efforts is presented along with a challenge for
      practitioners that the desired health and economic outcomes may well be better
      with this approach than with traditional programming strategies. The authors
      review the emerging areas of "positive psychology", "strength-based programming",
      "authentic happiness" and "good business" strategies as intervention strategies
      and methods for enhancing individual employee well-being. Research highlights and
      implications for the field are also presented.

PMID- 17233241
TI  - What do the parties' top 10 lists say about health care?
AB  - Three days after George W. Bush was inaugurated for his second term as president,
      Senate leaders from both sides of the aisle laid out their 2005 legislative
      agendas, and while their stated goals might appear to be the same, the contrast
      between the two sets of priorities couldn't be more striking.

PMID- 17233242
TI  - Cutting to the heart of the theory: the latest on charity care litigation.

PMID- 17233243
TI  - The future of APCs: a look at Medicare's 2005 changes and industry trends.
AB  - As the healthcare industry continues to struggle with an ever-evolving APC-based
      hospital outpatient PPS, it's important to be aware of some of the latest changes
      affecting providers and to recognize areas that may present particular challenges
      for private payers.

PMID- 17233244
TI  - Ready for prime time? Make your financial assistance policy a class act.
AB  - Today's regulatory climate makes it far from simple for hospitals to offer
      discounts to uninsured and indigent patients. Questions abound regarding whether
      offering such discounts might lead to reductions in Medicare payments for
      outliers, new technology, and bad debt. Offering waivers of coinsurance or
      deductibles may seem an attractive option, but routine waivers could implicate
      federal statutes regarding illegal remuneration and patient inducement. And
      across-the-board discounts to uninsured patients could change the calculation of
      a hospital's "usual charges," resulting in the hospital's violation of the
      statutory bar against having charges to Medicare that are "substantially in
      excess" of the "usual charges." The best course for hospitals is to have clearly
      defined financial assistance policies in place that reflect an awareness of all
      the related potential legal and regulatory concerns.

PMID- 17233245
TI  - Policies and practices for uninsured patients practical strategies.
AB  - Maintaining the healthcare organization's charitable mission to the community is
      best served by having formal policies in place. Must-haves include: A written
      charity care policy tailored to the organization. Financial assistance policies.
      Processes for identifying and communicating with patients who may need financial
      assistance. Formal discounting and collection policies and practices that take
      into account every patient's ability to pay.

PMID- 17233246
TI  - Are you a master of charge capture?
AB  - Healthcare providers are increasingly recognizing the importance of investing in
      the middle segment of the revenue cycle. Although the middle segment often
      represents an area of significant revenue leakage, it is also the area with the
      greatest potential to improve revenue recognition, through improved processes as
      well as the application of new technologies.

PMID- 17233247
TI  - Healthcare tipping points.
AB  - Cost and quality are two significant tipping points that will dramatically change
      the healthcare environment. Major changes in the way health care is delivered and
      financed are expected to occur over a relatively short period. Healthcare
      delivery will need to be reengineered. Key to accomplishing this objective is
      technology.

PMID- 17233248
TI  - Supply and conquer.
AB  - Several keys to West Jefferson Medical Center's supply chain success were:
      Developing a unified approach toward selecting and purchasing equipment and
      supplies that included strong physician representation. Using knowledge of vendor
      pricing with similar organizations to gain leverage during negotiations.
      Communicating the organization's financial status, data pertaining to products
      and vendors, and implications of purchasing decisions with medical staff in an
      open and honest fashion.

PMID- 17233249
TI  - Solving the communications breakdown.

PMID- 17233250
TI  - Is the federal government serious about health IT?
AB  - No matter what happens in Washington, the push for widespread adoption of
      electronic health records will not disappear. The value of health IT to providers
      in reporting the clinical outcomes data needed for quality-of-care incentives is
      too great to let this happen. What's more, an inquisitive public is demanding
      that the latest and greatest technology be used to improve patient safety.

PMID- 17233251
TI  - Niche markets show potential for increased revenue.

PMID- 17233252
TI  - U.S. hospitals see overall rise in bad debt, but regional differences are
      striking.

PMID- 17233253
TI  - Our agency doesn't take dying kids, do we? Pediatric patients in an adult hospice
      home care--a success story.

PMID- 17233254
TI  - Personal journey. Sarah's story.

PMID- 17233255
TI  - Peaceful ending.

PMID- 17233256
TI  - Dispelling the myth of intractable pain.

PMID- 17233257
TI  - It's great to be here. Former patient, Washington Post columnist lauds home care
      and hospice workers at NAHC's 25th Anniversary Meeting in Baltimore, Maryland.

PMID- 17233258
TI  - The hospice decision: making a wise choice.

PMID- 17233259
TI  - Hospice quality assessment and performance improvement (QAPI) project.

PMID- 17233260
TI  - E-prescribing's role in reducing medical errors.

PMID- 17233261
TI  - Celebrating milestones.

PMID- 17233262
TI  - Home health nurses influence physician referrals.

PMID- 17233263
TI  - Hospice programs: the same but...different.

PMID- 17233264
TI  - Creating and implementing effective incentive programs.

PMID- 17233265
TI  - Compassionate caring.
AB  - Beginning with a concerned society, from individuals, to visiting nurse
      associations, and to publicly traded corporations, home care and hospice have
      been meaningful threads in the American fabric for over a hundred years. Today,
      advances in technology, a burgeoning regulatory environment, and universal health
      care cost concerns make continued change expected and certain. While external
      health care environmental pressures incessantly shape the evolution of home care
      and hospice, a central value lives on in the heart of what we do as caregivers,
      in what is nowtermed our "industry". It is a value we must safeguard from
      evolutionary extinction.

PMID- 17233266
TI  - The huichol experience: healing wounds.

PMID- 17233267
TI  - A time to celebrate.

PMID- 17233268
TI  - [Malignant melanoma of the pinna. Importance of its diagnosis, treatment and
      prognostic factors].
AB  - About 25%-30% of the primary malignant melanomas occur in the head and neck
      region and of these less than 10% arise on the external ear, mainly on helix and
      the lobule of the pinna. Melanoma thickness and nodal or distant metastases are
      advers factors for its prognosis. We report a case of a tumor that affected the
      right pinna and was removed by our ENT, department with good evolution, being the
      patient free of disease after 5 years follow-up.

PMID- 17233269
TI  - [Metastases of pulmonary small cell carcinoma on cervical skin noted before the
      primary tumor].
AB  - We are reporting the case of a patient with final diagnosis of bronchopulmonar
      carcinoma of small cells who at first place assisted to E.N.T. Department due to
      a cervical node (adhered to the dermis) and hemoptysis of more than 2 months. We
      resected the neck mass which confirmed the presence ofa cutaneous metastases of
      an oat cell carcinome, being the patient after word ea sstudy by the Neumology
      Service, who found a righth lung tumor, of the same histological type. In spite
      of the treatment the patient die.

PMID- 17233270
TI  - [Indication for endoscopic procedures in maxiloethmoydal mucoceles].
AB  - The Functional Endoscopic Sinus Surgery has posibilitated a change in the
      diagnosis, treatment and postsurgical management of many nasosinusal diseases.
      Mucoceles of the paranasal sinuses are an ideal indication for performing these
      surgical procedures when good accesibility conditions are present. Under these
      circumstances, external approach, with the subsequent impairments and morbility,
      could be avoided. An endoscopically treated extensive maxilloethmoydal mucocele
      is presented and key points to endoscopic treatment indication are provided.

PMID- 17233271
TI  - [Reoperation because of ectopic parathyroid adenoma with previous removal of
      lipothymoma. Importance of intraoperative PTH].
AB  - Sometimes the surgery of hyperparathyroidism is not easy and the surgical team
      find difficulties to locate the pathological gland or glands. We report a case of
      primary hyperparathyroidism due to an ectopic parathyroid adenoma which required
      two interventions. First we removed what it seems an adenoma but resulted to be a
      lipotimoma. In the reintervention practiced one week later, having then the rapid
      or turbo intraoperative PTH and previous digital scintigraphy, it was possible to
      remove an adenoma histologically confirmed, with 3,5 cm diameter located in depth
      to right thyroid lobe towards the superior mediastinal straits. The postoperative
      evolution of the patient was satisfactory and no complications were registered.

PMID- 17233272
TI  - [Trend changes in the adenotonsillar surgery].
AB  - In order to evaluate possible trend changes in the epidemiological factors of
      adenotonsillar surgery, a total of 1,958 operations performed between 1992 and
      2002 were reviewed. RESULTS: One third of the operations were to remove tonsils
      in comparison with the two thirds that were to remove adenoids. Three procedures
      were used: 59% adenoidectomies, 28% adenotonsillectomies and 13% tonsillectomies.
      During the study period, the percentage of adenotonsillectomies decreased,
      whereas the number of adenoidectomies increased. In general, this kind of surgery
      is mainly performed on males. CONCLUSIONS: Although we have not discovered
      variations regarding gender and average age for the operations, adenotonsillar
      surgery has increased over recent years and the percentage ratio of the various
      procedures has altered as a result of new indications.

PMID- 17233273
TI  - [Disphagia secondary to cervical osteophytes].
AB  - Disphagia is a common cause of medical query in the ENT field, in which could be
      involved a variety of medical reason. One of those is the extrinsic compression
      of the digestive tract due to a tumoral process, or as the case we report,
      secundary to a large osteophyte at the anterior side of the cervical spine, after
      a surgical intervention in this area.

PMID- 17233274
TI  - [Laryngeal tuberculosis. Incidence between 1994 and 2004].
AB  - Tuberculosis is the chronic granulomatose most common infection of the larynx. It
      appears generally from pulmonary tuberculosis. It prevails in men. The most
      habitual symptomatology includes dysphony, odinophagy, referred otalgy and
      sometimes dispnea. The majority of patients use to have radiological pulmonary
      affectation to the diagnosis. The nodular exophitic or ulcerous lesions can be
      confused with carcinoma, therefore in these cases the anatomopathologic study is
      essential. The diagnosis is made with positive spit samples, specific
      characteristics of the thorax radiography and the positive biopsies of acid
      alcohol resistant bacillus. We present the patients diagnosed with laryngeal
      tuberculosis in our hospital between 1994 and 2004. We describe the diagnostic
      procedures realised and the adopted therapeutic attitude in every case and
      results.

PMID- 17233275
TI  - [Phlegmons and abscesses in the floor of mouth. Report of 10 cases and review of
      the literature].
AB  - We report a review about 10 cases of phlegmons-abscesses in the floor of mouth
      (Ludwig's angina) treated by our Service analyzing the following variables: Age,
      sex, time of evolution, personal antecedents, E.N.T. exploration, clinical
      symptoms, type of treatment and clinical evolution. This pathology represents one
      of the most severe forms of cervicofacial diffuse cellulitis; it requires an
      early diagnosis and therapy which can include an urgent tracheostomy ifthe airway
      is compromised.

PMID- 17233276
TI  - [Lobular capillary hemangioma on the floor of the mouth (pyogenic granuloma).
      Report of a case and literature review].
AB  - Lobular capillary hemangioma or pyogenic granuloma is a benign lesion with a
      focal reactive development of fibrovascular tissue and endotelial proliferation.
      It can appear to any age in different locations and usually has the aspect of a
      pediculate mass with or without ulceration zones on the area. Its treatment is
      the simple surgical removal and the control of the traumatic and infectious
      influential factors. We report a case of pyogenic granuloma on the floor of the
      mouth making a literature review at respect of that common clinical entity.

PMID- 17233277
TI  - [Neuro-otological manifestations as presentacion of type I Chiari malformation].
AB  - The type I Chiari malformation consists of an caudal descent of the cerebellar
      tonsils through the foramen magno towards the spinal cervical channel. The usual
      clinical presentation are occipital headaches and cervical pain, as well as some
      otoneurological symptoms. Among them are common dizziness and crisis of central
      positional vertigo in which down beating nystagmus can be observed. We present
      our experience with three cases presenting with neurotological manifestations in
      which MRI showed a type I Chiari malformation. Case 1: a patient of 24 years that
      had frequent instability, and common crisis ofpositional vertigo. It was possible
      to see the presence of positional down-beating nystagmus, of central
      characteristics, that improved after neurosurgical treatment. Case 2: patient of
      11 years who suffered from occasional headaches, dizziness and positional
      vertigo, without severe handicap, and did not need surgery. Case 3: lady of 63
      years who had common episodes of vertigo with head tilt, and unsteadiness during
      walks. Due to the coexistence of hydrocephalus and syringomyelia, surgery was
      indicated. A revision is done on otoneurological presentation of type I Chiari
      malformation, especially as differential diagnosis on central positional vertigo.

PMID- 17233278
TI  - [West Nile virus--causative agent of a zoonosis with increasing significance?].
AB  - The epidemic West Nile Virus (WNV) infections observed in the last years,
      particularly those in the USA in 1999 and the following years, have led to an
      increasing interest in this zoonotic infection. Here, the most prominent aspects
      of WNV biology and epidemiology are presented. Clinical signs observed in men and
      horses are described, as well as the current state of diagnostics and
      immunoprophylaxis. Preliminary results of investigations on the prevalence of WNV
      in Germany show that migrating birds have been in contact with WNV; there is
      however no indication for the presence of this virus. While WNV is endemic in
      many parts of the "Old World", thus inducing "natural immunity" in (migrating)
      birds and vertebrates, a susceptible bird population with no existing immunity
      against this virus was exposed in the "New World".

PMID- 17233279
TI  - [Influence of different surface machining treatments of resorbable implants made
      from different magnesium-calcium alloys on their degradation--a pilot study in
      rabbit models].
AB  - To examine the influence of different surface machining treatments of resorbable
      implants 3x5 mm cylinders of magnesium-calcium-alloys with plane, rough or sand
      blasted surface and different concentrations of calcium (0.4 %, 0.8 %, 1.2 % und
      2.0 %) were implanted into the distal femur condylus of 18 New Zealand White
      Rabbits. They were placed into the spongy-cortical passage. During six weeks the
      animals were examined daily and x-rayed weekly. After euthanasia the bone was
      explanted and scanned in a microcomputed tomograph. The implants were well
      tolerated by the rabbits, neither lameness nor signs of pain occured. Wound
      healing was mostly without complications. Eight of 36 implants (22 %) showed
      dehiscence of suture within first ten days, whereby implants made of 1,2 % MgCa
      were mainly affected (six of 12 cases, 50 %). At the place of insertion all
      implants induced obvious callus genesis which could be seen in MgCa 1,2-cylinders
      with plane surface and MgCa 0,8-cylinders with rough and sand blasted surface the
      most. Influence of different calcium concentrations on degradation behaviour
      could not be discovered. They showed different stages of resorption. Concerning
      the different surface machining treatments sand blasted implants showed the
      highest degree of degradation which could be seen by the totally loss of
      structure in micro-computed examinations. These implants also showed in six of 36
      cases a clinical occurrence of gas production. Rough implants showed an irregular
      degradation with high degree of resorption of some implants and signs of
      degradation only in the border area of others. Cylindricity maintained in plane
      implants. They showed loss of structure only in border areas.

PMID- 17233280
TI  - [Possibilities and limits of serological diagnosis in pig stocks in the case of
      Mycoplasma hyopneumoniae infection].
AB  - When conducting their investigations to diagnose infectious diseases in swine,
      practitioners are often forced to use reduced numbers of animals in their samples
      in order to minimize costs for farmers. A cross-sectional study was conducted
      approximating such field conditions to show the limits of interpretation with
      reduced sample sizes in case of Enzootic Pneumonia. Compared with other
      respiratory pathogens, Mycoplasma hyopneumoniae, the etiologic agent of Enzootic
      Pneumonia spreads very slowly, mainly when animals are in direct contact.
      Furthermore, the interpretation of serological results is difficult because
      several weeks must usually pass for serological reactions to become apparent.
      Serological testing is normally used to confirm a clinical diagnosis by detecting
      an increase in antibodies against the etiologic agent. Samples are collected at
      the beginning of disease and four to six weeks later. An increasing number of
      serological positive animals in a herd is usually interpreted as spread of
      infection. The ,,true" prevalence we observed in our investigation was used to
      make a statistical analysis describing the probability of detecting an increasing
      prevalence from 0.07 to 0.33 with a reduced sample size. We showed that the
      probability of detecting an increase of two seropositive animals was 44% if 5
      samples per group were analysed. When only 3 samples were analysed per group,
      this probability decreases to 21%. Compromise must be found between
      epidemiological necessary and financially acceptable sample size; this could be a
      minimum of 10 samples per age group.

PMID- 17233281
TI  - [Effect of fasting and refeeding on blood glutathione and lipid peroxide
      concentration of cockerels and pullets].
AB  - Changes of reduced glutathione (GSH) and TBARS (thiobarbituric acid-reactive
      products of lipid peroxidation) concentrations and activity of gamma
      glutamyltransferase (GGT, EC 2.3.2.2) in the blood of Lohman brown cockerels and
      pullets in response to 48 hour food deprivation and 24 hour refeeding were
      examined. The experiment was performed on 61-day-old chickens. Blood samples ware
      collected from the wing vein (v. brachialis) in heparinized tubes for three
      times: control sampling before fasting, then after 48 hour food deprivation and
      after refeeding for 24 hours. Blood GSH concentration after refeeding in
      cockerels was significantly higher compared with prefasting and fasting values.
      The concentration of GSH in female chickens was significantly lower after fasting
      as well as after refeeding compared with control values. In addition to that, in
      pullets GSH concentration in refeeding was higher than in fasting conditions. The
      level of TBARS in blood in female and male chickens after fasting and refeeding
      were significantly lower than the prefasting values. The GGT activity on
      cockerels after 48 hour food deprivation was significantly higher compared with
      control sampling and in chickens refeed for 24 hours, whereas in pullets
      significant difference was exhibit compared only with control values.
      Concentration of GSH in control sampling in cockerels compared with those in
      pullets was significantly lower. After 48 hours of fasting, the level of GSH was
      significantly higher in the cockerels than in the pullets. Results of TBARS
      concentration in the pullets were higher of control and fasting values than in
      the cockerels. The GGT activity of control sampling was significantly higher in
      male chicken. Lipid peroxidation in chickens of both sexes decreased with
      fasting, but prooxidative-antioxidative processes were more intensive in female
      chickens, probably because they were not reach sexual maturity.

PMID- 17233282
TI  - [80 years of the Society of Friends of the University of Veterinary Medicine
      Hannover].
AB  - The Society of Friends of the University of Veterinary Medicine Hannover was
      established in 1926, in times of severe economical distress. According to its
      statutes its main purpose from the beginning was to complement the governmental
      budget of the University. During its 80 years of existence the so called
      "Friendly Society" has contributed to overcome many financial shortages in
      research, clinics and institutes. In addition it supported veterinary students in
      need. Some aspects of the Society's history and activities will be communicated.

PMID- 17233283
TI  - The adjacent segment.

PMID- 17233284
TI  - Same-segment and adjacent-segment disease following posterior cervical
      foraminotomy.
AB  - OBJECT: The cervical foraminotomy was pioneered in the 1940s to address radicular
      symptoms via a posterior approach, but the long-term outcome has not been
      adequately studied. METHODS: The authors retrospectively analyzed data obtained
      from 303 patients (188 male and 115 female, mean age 49.2 years) who had
      consecutively undergone a single-level posterior foraminotomy for cervical
      radiculopathy between 1972 and 1992. The median follow-up duration was 7.1 years.
      The major end point studied was the development of symptomatic adjacent- or same
      segment disease. Incidence rates per 1000 person-years were calculated, and the
      natural history of the disease was predicted using Kaplan-Meier survivorship
      analysis. In 15 (4.9%) of 303 patients, symptomatic adjacent-segment disease
      developed, yielding a rate of 6.4/1000 person-years at risk. This included nine
      (2.9%) of 303 patients requiring reoperation, yielding a rate of 3.8/1000 person
      years. Kaplan-Meier survivorship analysis suggested a relatively stable annual
      0.7% rate for developing adjacent-segment disease, with a 10-year rate of 6.7%.
      Ten patients developed same-segment disease, yielding a risk rate of 3.9/1000
      person-years. Kaplan-Meier survivorship analysis demonstrated a 5- and 10-year
      risk rate of developing same-segment disease of 3.2 and 5.0%, respectively.
      CONCLUSIONS: Although additional study is needed, analysis of the present data
      suggests that posterior foraminotomy is associated with a low rate of same- and
      adjacent-segment disease.

PMID- 17233285
TI  - A comparison of changes over time in cervical foraminal height after tricortical
      iliac graft or polyetheretherketone cage placement following anterior discectomy.
AB  - OBJECT: The authors prospectively evaluated cervical foraminal height changes
      after anterior cervical discectomy and fusion. To their knowledge, this
      prospective study is the first in which foraminal height changes over time are
      compared following the placement of a tricortical graft or a polyetheretherketone
      (PEEK) cage. METHODS: The patients were randomly divided in two groups. In one
      group, 30 patients underwent anterior cervical microdiscectomy and free bone
      graft (FBG) insertion at 46 levels via the Smith-Robinson technique. The FBG was
      harvested from the right iliac crest. Another 35 patients underwent the same
      operation, but fusion was provided by the insertion of PEEK intervertebral cages
      at 41 levels. Fusion status and the C2-7 Cobb angle, interspace height, and
      foraminal height changes were observed on anterior, lateral, and oblique
      radiographs obtained at the 18-month follow-up examination. There were no
      differences between the groups with regard to clinical recovery, fusion status,
      and Cobb angle. A significant interspace height reduction was observed in the FBG
      group during the 1st postoperative month. In the FBG group, the mean heights (+/-
      standard deviation) of the foramina were 8.2 +/- 2.7 mm preoperatively, 10.8 +/-
      2.6 mm on postoperative Day 2, and 8.1 +/- 1.5 mm after 18 months of follow up.
      In the PEEK cage group, the mean heights were 8.4 +/- 2.8 mm preoperatively, 10.3
      +/- 1.1 mm on postoperative Day 2, and 9.6 +/- 1.2 mm after 18 months of follow
      up. The increase in foraminal height was significantly preserved at the 6th,
      12th, and 18th months in the cage group. CONCLUSIONS: In both groups the
      foraminal height increased sufficiently and the nerve root was decompressed
      postoperatively. The PEEK cages may provide sufficient preservation of foraminal
      height even 1.5 years after the operation.

PMID- 17233286
TI  - Cervical spondylotic myelopathy due to chronic compression: the role of signal
      intensity changes in magnetic resonance images.
AB  - OBJECT: Although there is agreement that low-intensity signal changes on T1
      weighted magnetic resonance (MR) images are a prognostic factor for poor outcome
      after surgical treatment of cervical myelopathy due to chronic cord compression,
      the role of high-intensity signal changes on T2-weighted images is still
      controversial. The aim of the present study was to determine whether T2-weighted
      MR imaging can help assess the prognosis of the disease. METHODS: A prospective
      case series study was conducted. The population comprised 67 patients who
      underwent surgery between 1994 and 2004 to treat myelopathy caused by chronic
      cervical cord compression. The mean follow-up period was 39 months. Preoperative
      and postoperative functional status was evaluated using a modified Japanese
      Orthopaedic Association scale, and the recovery rate was calculated using the
      Hirabayashi method. Magnetic resonance images were acquired 3 months or less
      before surgery. High-intensity signal changes were evaluated according to the
      extent of these changes on T2-weighted sequences; low-intensity T1-weighted
      signal changes were also evaluated. In patients with low-intensity changes on T1
      weighted images and in those with high-intensity changes spanning multiple levels
      on T2-weighted images, the authors documented a poor functional recovery.
      CONCLUSIONS: Multisegmental high-intensity change on T2-weighted MR imaging is a
      more sensitive indicator of outcomes than T1-weighted signal changes because of
      its higher frequency in patients with advanced myelopathy.

PMID- 17233287
TI  - Corpectomy followed by the placement of instrumentation with titanium cages and
      recombinant human bone morphogenetic protein-2 for vertebral osteomyelitis.
AB  - OBJECT: The treatment of vertebral osteomyelitis includes antibiotics with or
      without surgical intervention. The decision to place instrumentation into an
      infected spinal column remains controversial. The use of recombinant human bone
      morphogenetic protein-2 (rhBMP-2) in patients with osteomyelitis is also
      extremely controversial. The authors review their experience in performing
      corpectomy and fusion with titanium cages and rhBMP-2 in patients with vertebral
      instability and/or neurological compromise due to vertebral osteomyelitis.
      METHODS: Data obtained in 15 patients treated between 2001 and 2005 were included
      in this analysis. Nine patients presented primarily with axial pain and six with
      radiculopathy or myelopathy. Seven patients had an associated epidural abscess.
      The cervical spine was affected in six patients, the thoracic spine in five, and
      the lumbar spine in four. All patients underwent corpectomy of the involved
      vertebral bodies; the authors then performed spinal reconstruction, placing a
      titanium cage-plate system with morcellized allograft/autograft and rhBMP-2. In
      10 patients, supplemental posterolateral screw-rod fixation was conducted. A one
      level corpectomy was performed in one patient, a two-level corpectomy in 13, and
      a six-level corpectomy in one. A morcellized allograft and rhBMP-2-filled
      titanium cage was used in 10 patients, and an autograft and rhBMP-2-filled cage
      in five patients. The most common pathogen was Staphylococcus aureus. All
      patients received intravenous antibiotics for at least 6 weeks postoperatively,
      and life-long antibiotic therapy was required in three patients with
      coccidiomycoses, candida, and tuberculosis osteomyelitis, respectively. There
      were no recurrent infections. Radiography demonstrated evidence of fusion in all
      patients at the last follow-up examination. The mean follow-up period was 20
      months. CONCLUSIONS: Corpectomy followed by titanium cage-plate reconstruction
      and the placement of rhBMP-2 may be a safe and effective treatment for selected
      patients with vertebral osteomyelitis. This surgical therapy does not appear, at
      least based on preliminary results, to lead to recurrent hardware infections.
      Based on the results obtained in this limited series, the authors found that
      rhBMP-2 can be used in the setting of active infection with excellent fusion
      rates and without complication. The morbidity associated with the autograft donor
      site is avoided when using cages. Antibiotic therapy tailored to the specific
      organism should be continued for at least 6 weeks after surgery, and life-long
      therapy is required in cases of fungal or tuberculosis infections.

PMID- 17233288
TI  - Foramen arcuale: anatomical study and review of the literature.
AB  - OBJECT: The neurosurgical literature is lacking information on the so-called
      foramen arcuale. When this foramen is present, the vertebral artery (VA) travels
      through it after exiting the transverse foramen of the atlas and prior to
      entering the cranium. METHODS: The authors performed a study in 60 cadavers to
      determine the incidence of the foramen arcuale and ascertain morphometric
      information on its anatomy. In specimens in which the foramen arcuale was
      observed, the authors studied the relationship between it and the VA. The authors
      identified a foramen arcuale in 5% of specimens. The mean length and thickness of
      the osseous struts that converted the groove for the VA into the foramen arcuale
      were 7.0 and 2.0 mm, respectively. The mean area of the identified foramina was
      14.2 mm2. The mean area of the ipsilateral C-1 transverse foramina was 18 mm2 in
      specimens with a foramen arcuale. The mean measurements of the proximal,
      intraforaminal (foramen arcuale), and distal diameter of the V3 segment of the VA
      at the level of the foramen arcuale were 6, 4, and 5 mm, respectively. In all
      specimens the authors noted that the intraforaminal part of the V3 segment was
      grossly compressed. CONCLUSIONS: The authors found that the foramen arcuale may
      compress the V3 segment of the VA. Based on their postmortem study, however, they
      cannot conclude that compression at this location results in symptomatic VA
      insufficiency. Based on their review of the literature, it seems that symptomatic
      compression of the VA at this location may be alleviated in some patients with
      decompressive procedures.

PMID- 17233289
TI  - Gene transfer of insulin-like growth factor-I providing neuroprotection after
      spinal cord injury in rats.
AB  - OBJECT: Insulin-like growth factor-I (IGF-I) has been shown to be a potent
      neurotrophic factor that promotes the growth of projection neurons, dendritic
      arborization, and synaptogenesis. Its neuroprotective roles may be coordinated by
      activation of Akt, inhibition of glycogen synthase kinase-3beta (GSK-3beta), and
      thus inhibition of tau phosphorylation. The authors investigated the role and
      mechanism of IGF-I gene transfer after spinal cord injury (SCI). METHODS: Studies
      were performed in 40 male Sprague-Dawley rats after spinal cord hemisection. The
      authors conducted hydrodynamics-based gene transfection in which an IGF-I plasmid
      was rapidly injected into the rat's tail vein 30 minutes after SCI. The animals
      were randomly divided into four groups: Group I, sham operated; Group II, SCI
      treated with pCMV-IGF-I gene; Group III, SCI treated with vehicle pCMV-LacZ gene;
      and Group IV, SCI only. The results showed that IGF-I gene transfer promoted
      motor recovery, antiinflammatory responses, and antiapoptotic effects after SCI.
      Using techniques of Western blotting and immunohistochemistry, the authors
      assessed the mechanism of IGF-I gene transfer after SCI in terms of activation of
      Akt, inhibition of GSK-3beta, attenuation of p35, and inhibition of tau
      phosphorylation. Moreover, they found that IGF-I gene transfer could block
      caspase-9 cleavage, increase Bcl-2 formation, and thus inhibit apoptosis after
      SCI. CONCLUSIONS: The intravenous administration of IGF-I after SCI activated
      Akt, attenuated GSK-3beta, inhibited p35 activation, diminished tau
      hyperphosphorylation, ended microglia and astrocyte activation, inhibited neuron
      loss, and significantly improved neurological dysfunction. Furthermore, IGF-I
      attenuated caspase-9 cleavage, increased Bcl2, and thus inhibited apoptosis after
      SCI.

PMID- 17233290
TI  - Deep vein thrombosis due to migrated graft bone after posterior lumbosacral
      interbody fusion. Case report.
AB  - The authors report the case of an 83-year-old woman with refractory sciatica
      attributable to isthmic spondylolisthesis at L-5. Her symptoms were successfully
      improved after posterior lumbar interbody fusion (PLIF) at L5-S1; however,
      notable swelling in her left leg suddenly developed 2 days postoperatively.
      Anterior migration of a fragment of bone graft was demonstrated on computed
      tomography scanning, and there was obvious occlusion of the left common iliac
      vein (CIV) on magnetic resonance venography. Ultrasonography revealed a thrombus
      in the left CIV at the site of compression. To prevent a pulmonary embolism
      during manipulation of the affected vein, an inferior vena cava filter was placed
      just before excision of the migrated bone fragment. The swelling in the patient's
      leg subsided quickly after the surgery, and she was treated with heparin and
      warfarin to prevent recurrent deep vein thrombosis (DVT). Six months after the
      second surgery, complete restoration of blood flow to the left CIV and no
      recurrence of DVT were demonstrated on magnetic resonance venography. Especially
      in elderly patients with degenerative disc disease, excessive curettage and
      impaction of disc materials during the PLIF procedure may cause migration of bone
      graft fragments. Surgeons should be aware of the possible vascular complications
      of PLIF.

PMID- 17233291
TI  - Expansile, enhancing cervical cord lesion with an associated syrinx secondary to
      demyelination. Case report and review of the literature.
AB  - The authors describe the case of a patient with an enhancing, intramedullary
      cervical spinal cord lesion and associated syrinx. Biopsy sampling of the
      cervical lesion was performed, and the histological findings were consistent with
      a demyelinating process supporting the diagnosis of multiple sclerosis (MS).
      Syrinx formation associated with demyelinating disease has only been described in
      isolated cases, almost exclusively in Japanese patients with MS. A 22-year-old
      woman of Caribbean descent presented with a subacute, progressive myelopathy
      including symptoms of pain and weakness in all extremities, bladder incontinence,
      and the inability to ambulate. Magnetic resonance imaging of the brain and spinal
      cord demonstrated an enlarged cervical cord with enhancement and central
      cavitation consistent with a syrinx. The patient underwent a C3-7 laminoplasty
      and placement of a dural graft for cord decompression as well as fenestration of
      the central syrinx. Biopsy sampling of the lesion was performed, and the
      histopathological analysis, in conjunction with subsequent laboratory and
      diagnostic testing, supported the diagnosis of demyelinating disease. After
      treatment with a course of high-dose dexamethasone and inpatient rehabilitation
      therapy, the patient demonstrated significant clinical improvement. Spinal cord
      involvement is not uncommon in patients with demyelinating disease; however,
      enhancing lesions associated with extensive tissue loss and syrinx formation have
      rarely been reported. For the consulting neurological surgeon, demyelinating
      disease should be included in the differential diagnosis of such lesions given
      the level of complexity and risk to the patient associated with open biopsy of
      the spinal cord.

PMID- 17233292
TI  - An extramedullary plasmacytoma originating from the thoracic spinal cord:
      magnetic resonance imaging findings. Case report.
AB  - Extramedullary plasmacytoma (EMP) is a rare tumor. The authors report a case of
      an EMP originating in the thoracic spinal cord. To their knowledge this is the
      first report in which an EMP originating in this location is described.
      Isointense and hyperintense signals were seen on T1-weighted and T2-weighted
      magnetic resonance images, respectively, with marked irregular contrast
      enhancement and extensive edema. No evidence of bone marrow involvement or
      multiple myeloma was noted. The histological findings were compatible with an
      EMP.

PMID- 17233293
TI  - Ventriculoperitoneal shunt failure causing myelopathy in a patient with bilateral
      jugular vein occlusion. Case report.
AB  - The authors describe the case of a 36-year-old woman with bilateral internal
      jugular vein occlusion, hydrocephalus, and Dandy-Walker variant who presented
      with myelopathy that was ultimately attributed to ventriculoperitoneal (VP) shunt
      failure. Computed tomography (CT) angiography of the head and neck revealed
      epidural venous engorgement within the cervical spine, greater that 50% narrowing
      of the C2-5 spinal canal, and compression of the cervical spinal cord. After
      successful shunt revision, postoperative CT angiography revealed decreased venous
      engorgement as well as decompression of the cervical spinal cord, and the
      patient's myelopathy improved. This case represents a fascinating clinical
      presentation of VP shunt failure, highlighting the physiological importance of
      the external jugular pathways involved in cerebral venous drainage.

PMID- 17233294
TI  - Upper cervical myelopathy due to arachnoiditis and spinal cord tethering from
      adjacent C-2 osteomyelitis. Case report and review of the literature.
AB  - Myelopathy caused by a spinal cord infection is typically related to an adjacent
      compressive lesion such as an epidural abscess. The authors report a case of
      progressive high cervical myelopathy from spinal cord tethering caused by
      arachnoiditis related to an adjacent C-2 osteomyelitis. This 70-year-old woman
      initially presented with a methicillin-sensitive Staphylococcus aureus
      osteomyelitis involving the C-2 odontoid process. She was treated with
      appropriate antibiotic therapy but, over the course of 4 weeks, she developed
      progressive quadriparesis. A magnetic resonance image revealed near-complete
      resolution of the C-2 osteomyelitis, but new ventral tethering of the cord was
      observed at the level of the odontoid tip. She subsequently underwent open
      surgical decompression and cord detethering. Postoperatively she experienced
      improvement in her symptoms and deficits, which continued to improve 1 year after
      her surgery. To the authors' knowledge, this is the first reported case of
      progressive upper cervical myelopathy due to arachnoiditis and cord tethering
      from an adjacent methicillin-sensitive S. aureus C-2 osteomyelitis.

PMID- 17233295
TI  - Flexion myelopathy of the thoracic spine. Case report.
AB  - The authors report a rare case of surgically treated symptomatic thoracic
      kyphosis caused by dynamic compression in an elderly man. Myelopathy due to
      thoracic kyphosis has been reported in patients with congenital kyphosis,
      Scheuermann dorsal kyphosis, and Cushing disease, but to the authors' knowledge
      this is the first report of dynamic kyphosis in an elderly person. This otherwise
      healthy 84-year-old man presented with a 2-year history of progressive difficulty
      in walking and bilateral leg dysesthesia. Despite several cervical and lumbar
      surgeries, his symptoms gradually worsened. A radiological examination revealed
      severe thoracic kyphosis, with a lateral Cobb angle of 59 degrees from T-2 to T
      12. On a dynamic computed tomography (CT) myelogram, severe thoracic spinal cord
      draping and stretching on flexion was demonstrated. On extension, however,
      imaging studies failed to show draping or stretching. Posterior corrective fusion
      was performed with instrumentation from T-2 to T-9. Postoperative CT myelography
      demonstrated no significant spinal cord compression with restoration of the
      cerebrospinal fluid space anterior to the spinal cord, and the successful
      correction of the kyphosis to 44 degrees. The patient's neurological sequelae
      gradually resolved throughout 6 months of follow up.

PMID- 17233296
TI  - Uterus-like mass of mullerian origin in the lumbosacral region causing cord
      tethering. Report of two cases.
AB  - The presence of mullerian-origin tissue in the lumbosacral region is extremely
      uncommon. The authors report two cases of mullerian-origin tissue in that region.
      In the first case a 33-year-old woman harbored a conus medullaris mass lesion.
      Spinal dysraphism, tethered cord syndrome (TCS), and diastematomyelia were also
      present. In the second case a 24-year-old woman presented with low-back pain and
      a conus medullaris lesion, which was a cause of the TCS. Pathological examination
      in both cases revealed a uterus-like structure with evidence of fresh and old
      hemorrhage. The rarity of this lesion and its association with diastematomyelia
      requires documentation.

PMID- 17233297
TI  - Calcific retropharyngeal tendinitis: a frequently missed diagnosis. Case report.
AB  - Neck pain is a common presentation in emergency departments that requires the
      exclusion of serious underlying pathological entities. Acute calcific
      retropharyngeal tendinitis is a rare and underrecognized cause of atraumatic neck
      pain and stiffness. Although this entity has been reported previously, it is
      often poorly recognized and is often confused with other more serious lesions,
      such as infectious, traumatic, and neoplastic conditions. Clinically, it can be
      very difficult to distinguish from these three disorders, and a definitive
      diagnosis can only be established using imaging studies. A knowledge of the
      characteristic clinical spectrum and, most importantly, its imaging features is
      crucial for making the correct diagnosis of this uncommon cause of neck pain. The
      authors present their experience with one case to highlight the characteristic
      findings of this disorder on plain radiography, computed tomography, and magnetic
      resonance imaging.

PMID- 17233298
TI  - Spontaneous regression of a discal cyst. Case report.
AB  - The authors describe a case of a discal cyst that resolved almost completely
      without direct intervention. Discal cysts are rare, with the authors of only a
      few case reports describing this entity. These reports all identify at least some
      intervention performed for alleviation of the symptoms, including open surgery,
      minimally invasive surgery, or percutaneous puncture with aspiration. The authors
      report on a 35-year-old man with radiculopathy who presented with a discal cyst
      and was treated with a routine epidural injection and selective nerve root block.
      Within 5 months, the discal cyst showed dramatic regression on magnetic resonance
      imaging and the patient's symptoms improved. The natural history of this
      pathological entity is unknown, and to the authors' knowledge this is the first
      detailed report of the regression of a discal cyst without surgery or aspiration.

PMID- 17233299
TI  - Discal cysts of the lumbar spine. Report of five cases.
AB  - Discal cysts are rare lesions that can result in refractory sciatica. Because
      they are so rare, their exact origin and details of the clinical manifestations
      are still unknown. The authors report on five men treated for discal cysts. The
      mean age of the patients at the time of the surgery was 32 years (range 25-38
      years). All patients suffered from lower-extremity pain and the results of the
      straight leg-raising test were positive in all cases. Three patients reported
      motor weakness and four had sensory disturbance-symptoms similar to those found
      in patients with lumbar disc herniation. Magnetic resonance imaging demonstrated
      spherically shaped extradural lesions of various sizes with low and high signal
      intensities on T1- and T2-weighted images, respectively. Discography revealed
      obvious communication between the cyst and the intervertebral disc with
      reproducible leg pain in all patients. All patients underwent posterior
      decompression and excision of the cysts either with or without additional
      discectomy. The radicular symptoms were remarkably improved in all patients
      immediately after surgery, and no recurrent lesions were noted during follow up.

PMID- 17233300
TI  - Application of a novel headrest system for odontoid screw fixation. Technical
      note.
AB  - The authors describe a unique headholder device adapted to facilitate the
      placement of anterior odontoid screws. The patient's head is affixed in the
      headholder equipped with an articulating arm that can be placed in a paramedian
      fashion. This configuration rigidly fixates the head and provides an unencumbered
      open-mouth view of the odontoid using radiographic images, thus making screw
      placement easier.

PMID- 17233301
TI  - Combined percutaneous transpedicular tumor debulking and kyphoplasty for
      pathological compression fractures. Technical note.
AB  - Percutaneous balloon kyphoplasty has become a widely adopted treatment option for
      patients with pain due to pathological compression fractures. One potential risk
      of the procedure is the displacement of tumor into the spinal canal and resulting
      spinal cord or cauda equina injury during inflation of the balloon prior to
      polymethylmethacrylate (PMMA) placement. In addition, the presence of any
      remaining tumor between the PMMA and the fractured cortical bone can lead to
      suboptimal improvement in stabilization and subsequent pain relief. The authors
      describe a technique to remove tumor from within the vertebral body (VB) through
      a percutaneous working channel prior to kyphoplasty balloon inflation and
      augmentation. The technique was successfully used in all three patients who had
      presented with pain, and the pain improved in all three cases. There was no
      extravasation of PMMA into the spinal canal in any case. A combined VB tumor
      debulking and kyphoplasty technique offers the ability to improve the placement
      of PMMA within the diseased vertebral body, potentially leading to increased
      safety as well as clinical effectiveness for stabilization of these fractures.

PMID- 17233302
TI  - Ossification of ligamentum.
AB  - OBJECT: The authors evaluated different surgical methods used to treat thoracic
      ossification of the ligamentum flavum (OLF). METHODS: Data obtained in 40
      patients who underwent posterior decompression for thoracic myelopathy caused by
      thoracic OLF were studied retrospectively. There were 32 men and eight women. All
      patients underwent posterior decompression in which laminoplasty was performed or
      laminectomy combined with lateral fusion. Every surgical specimen was stained
      with H and E, and scanning electron microscopy was performed in 20 cases. The
      mean follow-up period was 28 months. Postoperative outcomes were evaluated using
      a recovery scale based on the Japanese Orthopaedic Association classification.
      There were a total of 168 ossified segments in this series, 77.4% of which were
      located in the lower thoracic spine. Marginal osteophyte formation was found in
      36 patients; in 32 of the 36 patients, these marginal osteophytes were located at
      the intervertebral space either higher or lower than the ossified segment.
      Scanning electron microscopy showed elastic fiber breakdown, proliferation of
      collagenous fibers, calcification, and OLF in the same microscopy region.
      Laminoplasty was performed in four patients. In three cases surgery resulted in
      unchanged or worse outcome (increased kyphotic deformity in two), and in one it
      resulted in good outcome. Laminectomy combined with lateral fusion was performed
      in 36 patients, in 30 cases of which it resulted in a good or fair outcome, and
      increased kyphotic deformity in only one. Of these 36 laminectomy-treated
      patients, an en bloc laminectomy-treated procedure was performed in 16 patients;
      in 11 of the 12 patients with lateral or diffuse-type lesions the surgery
      resulted in a good or fair outcome. En bloc laminectomy, however, seems
      ineffective in the treatment of patients with thickened, nodular-type thoracic
      OLF, as the procedure resulted in worse outcome in two of the four patients. The
      authors have thus developed a new modality of laminectomy that they have termed
      "separating laminectomy," which they performed in 16 patients with thickened,
      nodular-type OLF; in 13 cases it resulted in a good or fair outcome, and in only
      one case did it result in a worse outcome. CONCLUSIONS: The pathogenesis of
      thoracic OLF is mainly due to the localized mechanical stress on the ligament.
      Laminectomy combined with lateral fusion is the treatment of choice for thoracic
      OLF; furthermore, in terms of the configuration of the ossified lesion, en bloc
      laminectomy is suitable for the treatment of lateral-type and diffuse-type OLF,
      and the separating laminectomy is suitable for the thickened, nodular-type OLF.

PMID- 17233303
TI  - Nonoperative treatment.
AB  - OBJECT: Despite extensive published research on thoracolumbar burst fractures,
      controversy still surrounds which is the most appropriate treatment. The
      objective of this study was to evaluate the scientific literature on operative
      and nonoperative treatment of patients with thoracolumbar burst fractures and no
      neurological deficit. METHODS: In their search of the literature, the authors
      identified all possible relevant studies concerning thoracolumbar burst fracture
      without neurological deficit. Two independent observers performed study
      selection, methodological quality assessment, and data extraction in a blinded
      and objective manner for all papers identified during the search. In a synthesis
      of the literature, the authors obtained evidence for both operative and
      nonoperative treatments. CONCLUSIONS: There is a lack of evidence demonstrating
      the superiority of one approach over the other as measured using generic and
      disease-specific health-related quality of life scales. There is no scientific
      evidence linking posttraumatic kyphosis to clinical outcomes. The authors found
      that there is a strong need for improved clinical research methodology to be
      applied to this patient population.

PMID- 17233304
TI  - Craniopharyngioma.

PMID- 17233305
TI  - Pediatric craniopharyngiomas: classification and treatment according to the
      degree of hypothalamic involvement.
AB  - OBJECT: The current treatment of craniopharyngiomas is evolving into one of a
      multimodal approach in which the aim is disease control and improved preservation
      of quality of life (QOL). To date, an appropriate classification system with
      which to individualize treatment is absent. The objectives of this study were to
      identify preoperative prognostic factors in patients with craniopharyngiomas and
      to develop a risk-based treatment algorithm. METHODS: The authors reviewed data
      obtained in a retrospective cohort of 66 children (mean age 7.4 years, mean
      follow-up period 7 years) who underwent resection between 1984 and 2001.
      Postoperative recurrence rates, vision status, and endocrine function were
      consistent with those reported in the literature. The postoperative morbidity was
      related to hypothalamic dysfunction. The preoperative magnetic resonance imaging
      grade, clinically assessed hypothalamic function, and the sugeon's operative
      experience (p = 0.007, p = 0.047, p = 0.035, respectively) significantly
      predicted poor outcome. Preoperative hypothalamic grading was used in a
      prospective cohort of 22 children (mean age 8 years, mean follow-up period 1.2
      years) treated between 2002 and 2004 to stratify patients according to whether
      they underwent gross-total resection (GTR) (20%), complete resection avoiding the
      hypothalamus (40%), or subtotal resection (STR) (40%). In cases in which residual
      disease was present, the patient underwent radiotherapy. There have been no new
      cases of postoperative hyperphagia, morbid obesity, or behavioral dysfunction in
      this prospective cohort. CONCLUSIONS: For many children with craniopharyngiomas,
      the cost of resection is hypothalamic dysfunction and a poor QOL. By using a
      preoperative classification system to grade hypothalamic involvement and stratify
      treatment, the authors were able to minimize devastating morbidity. This was
      achieved by identifying subgroups in which complete resection or STR, performed
      by an experienced craniopharyngioma surgeon and with postoperative radiotherapy
      when necessary, yielded better overall results than the traditional GTR.

PMID- 17233306
TI  - Shunt infection.

PMID- 17233307
TI  - Shunt infection: is there a near-miss scenario?
AB  - OBJECT: The aim of this study was to establish whether microbiological
      contamination at the time of shunt insertion can be detected and used to predict
      the likelihood of subsequent shunt infection. METHODS: A prospective study of
      pediatric patients undergoing primary shunt insertion was undertaken. Following
      the protocol devised for this study, three swab samples were collected from the
      surgical wounds during each procedure. These samples were incubated and
      subcultured, and the isolates were identified and stored. In patients who
      subsequently presented with clinical evidence of shunt infection, cerebrospinal
      fluid (CSF) was analyzed using microscopy, tissue cultures, and sensitivity
      testing. The organisms isolated at the time of shunt insertion and those
      responsible for subsequent shunt infection were then compared. The study
      population consisted of 107 pediatric patients. Because one patient underwent
      placement of an additional contralateral shunt system, there were 108 total shunt
      insertions yielding 325 swab samples. Organisms were identified in cultures of 50
      swab samples (15%) obtained in 40 patients (37%). In seven of these 40 patients
      (17.5%) a CSF infection subsequently developed. In only one patient was the
      infectious organism the same as that isolated from the swab specimens. In an
      additional six patients (8.8%) a CSF infection occurred despite the lack of
      growth in the cultures from intraoperative swab samples. CONCLUSIONS: The
      organisms responsible for shunt infection were rarely detected in the operative
      wound at the time of shunt insertion, leading the authors to conclude that the
      vulnerable period for bacterial colonization of shunts may not be restricted to
      the operative procedure as is commonly believed, but may extend throughout the
      postoperative period of wound healing. These findings have implications not only
      for a better understanding of the cause of shunt infections but also for the
      development of strategies to prevent them.

PMID- 17233308
TI  - Surgical treatment of epilepsy in Sturge-Weber syndrome in children.
AB  - OBJECT: The authors sought to analyze the success rate of surgery in the
      management of medically intractable epilepsy in children with Sturge-Weber
      syndrome and to determine whether the extent and timing of surgery affected
      seizure and developmental outcomes. METHODS: The authors performed a
      retrospective review of 27 children who underwent surgery at their institution
      for medically resistant epilepsy, and they examined the outcomes with regard to
      epilepsy control and neuropsychological development. Seventeen children (63%)
      experienced onset of their epilepsy when they were younger than 1 year of age.
      These patients were significantly more likely to have hemiparesis (p < or =0.001)
      and status epilepticus (p < or = 0.001) and be developmentally delayed (p < or =
      0.025) than children whose epilepsy started later in life. Eight patients
      underwent a hemispherectomy (either anatomical or functional), and complete
      resolution of epilepsy was noted in all. Of the 19 patients in whom a focal
      resection was performed, 11 (58%) became seizure free. The 10 children in whom
      there was residual disease were more likely to have continuing epilepsy than the
      nine whose lesions were completely excised (p< or = 0.05). Seventeen children
      exhibited improvement in their developmental status following surgery. This
      improvement was significantly affected by completeness of resection (p< or =
      0.05) and age at surgery (p< or = 0.009). Seizure freedom per se was not affected
      by the timing of surgery. CONCLUSIONS: Medically intractable epilepsy in children
      can be treated effectively by surgery. The degree of resection or disconnection
      of diseased tissue, but not patient age at the time of surgery, is an important
      factor in achieving epilepsy control. Early surgery is more likely to improve
      developmental outcome.

PMID- 17233309
TI  - Neuroendoscopic treatment of multiloculated hydrocephalus in children.
AB  - OBJECT: The authors performed a retrospective analysis of data obtained in a
      series of 30 patients suffering from multiloculated hydrocephalus and treated
      endoscopically. The goal of the study was to evaluate the effectiveness of
      neuroendoscopic treatment as an alternative to the placement of multiple shunts
      to relieve intracranial hypertension, to simplify the shunt system, and to reduce
      the high rate of shunt revision. METHODS: The endoscopic procedures included
      intraventricular septum fenestration, aqueductoplasty, Monro foraminoplasty, and
      third ventriculostomy. The patients were divided into two groups: Group A
      included 23 children in whom a shunt was already in place at the time of
      endoscopy, and Group B included seven children in whom a shunt had never been
      placed. The control of hydrocephalus by a single shunt placement or the absence
      of a shunt was achieved in 25 (83.3%) of 30 children. In Group A, five children
      no longer had shunts, 14 needed a single shunt, three required two shunts, and
      one required three shunts. The mean preendoscopy shunt revision rate in this
      group decreased from 2.07/year to 0.35/ year following the endoscopic procedure.
      Seven patients required endoscopic reoperations (endoscopic reoperation rate
      0.31/year, total reoperation rate [shunt revisions plus endoscopic reoperation]
      0.66/year). In Group B, three children did not require shunts, three needed a
      single shunt, and one required two shunts. Two patients required repeated
      endoscopic surgery (endoscopic reoperation rate 0.19/year), and two patients
      required shunt revisions (shunt revision rate 0.07/year) (total operation rate
      0.26/year). CONCLUSIONS: Neuroendoscopic procedures are a valid alternative to
      shunt revision in the management of multiloculated hydrocephalus. Early diagnosis
      comprising close monitoring with high-resolution magnetic resonance imaging and
      early treatment are the keys of success.

PMID- 17233310
TI  - Neuroprotective effect of the surfactant poloxamer 188 in a model of intracranial
      hemorrhage in rats.
AB  - OBJECT: Neuronal injury remains a leading cause of morbidity in both neonates and
      adults with injuries induced by intracranial hemorrhage, ischemia-reperfusion,
      and excitotoxicity. To date, a number of neuroprotective strategies have been
      evaluated, but they have shown little benefit. Poloxamer 188 (P-188), a membrane
      active triblock copolymer, has been studied extensively as a cell-membrane
      sealant. The authors used an animal model to study the neuroprotectant effects of
      P-188 administered by intracisternal (IC) injection after experimentally induced
      intraparenchymal hemorrhage. METHODS: Sprague-Dawley rats received an IC
      injection of either P-188 or vehicle (artificial cerebrospinal fluid) 10 minutes
      after striatal infusion of 50 microl of autologous blood. Animals from both
      treatment groups were killed either 2 or 7 days later. In a second experiment,
      after striatal blood infusion and early IC injection of either P-188 or vehicle,
      animals received daily IC injections of either P- 188 or vehicle for 5 days, and
      were killed 7 days after induction of the experimental hemorrhage. Striatal
      tissues were histologically analyzed for neuronal loss, and lesion volumes were
      determined. Lesion volumes in the animals that received a single dose of P-188
      were significantly smaller (mean+/-standard deviation 18.3+/-4.3 mm(3), six rats;
      p = 0.04) than those in the control group (31.4+/-4.3 mm(3), seven rats) when
      measured 2 days postinjection; however, no difference in lesion volumes was
      present 7 days postinjection. Lesion volumes in the animals who received 5 days
      of daily P-188 injections were significantly smaller (1.50+/-0.58 mm(3), 10 rats;
      p = 0.04) than those in the corresponding control group (5.04+/-1.85 mm(3), eight
      rats) when measured at 7 days. CONCLUSIONS: A single dose of P- 188 protects
      against early neuronal loss after hemorrhage but has no effect on long-term
      hemorrhage-induced neuronal loss. However, repeated daily P-188 treatment appears
      to produce effective long-term neuronal protection.

PMID- 17233311
TI  - Rupture of brainstem cyst with clinical benefit after head injury. Case report.
AB  - The authors report an interesting case of the rupture of a brainstem cyst
      following blunt head trauma. They discuss the case, review reports of similar
      events, and suggest a possible mechanism by which the cyst could have resolved
      without surgery.

PMID- 17233312
TI  - Immediate resolution of tonsillar herniation and severe cervicothoracic
      syringomyelia after third ventriculostomy for hydrocephalus caused by a brainstem
      tumor. Case report.
AB  - The authors report the case of a patient who harbored a large intrinsic brainstem
      tumor associated with tonsillar herniation, hydrocephalus, and severe
      cervicothoracic syringomyelia. This 15-year-old girl had a 2-month history of
      progressively worsening headaches. Magnetic resonance imaging showed a large
      tumor in the dorsolateral brainstem accompanied by hydrocephalus as well as a
      cervicothoracic syrinx extending to the level of T-8. She underwent endoscopic
      third ventriculostomy that resulted in a marked decrease in the ventricle size as
      well as complete resolution of the syrinx and tonsillar herniation within 4 days.
      Clinical and neuroimaging findings of the case along with a pertinent literature
      review are presented.

PMID- 17233313
TI  - Chiari-like tonsillar herniation associated with intracranial hypotension in
      Marfan syndrome. Case report.
AB  - The authors describe the case of a 12-year-old girl with Marfan syndrome, sacral
      dural ectasia, and tonsillar herniation, who presented with headache. Initially,
      it was hypothesized that the headaches were secondary to the tonsillar
      herniation, and the patient consequently underwent surgical decompression of the
      foramen magnum. Postoperatively, the patient's condition did not improve, and
      additional magnetic resonance (MR) imaging demonstrated evidence of a
      cerebrospinal fluid (CSF) leak at the level of the dural ectasia. It was surmised
      that the girl's symptoms were due to spontaneous intracranial hypotension (SIH)
      and that the tonsillar herniation was caused by the leakage. The patient
      responded well to application of a blood patch at the level of the demonstrated
      leak, and her headache resolved. This appears to be the first reported case of a
      patient with Marfan syndrome presenting with a symptomatic spontaneous CSF leak
      complicated by tonsillar herniation. In this rare association of SIH and
      connective tissue disorders, recognition of the clinical signs and typical MR
      imaging features of SIH may lead to more appropriate and less invasive treatment,
      potentially avoiding surgery.

PMID- 17233314
TI  - Lemierre syndrome complicated by cavernous sinus thrombosis, the development of
      subdural empyemas, and internal carotid artery narrowing without cerebral
      infarction. Case report.
AB  - Lemierre syndrome is an extremely rare complication of mild-to-moderate
      pharyngeal infections. The authors present an unusual case of Lemierre syndrome
      in a 16-year-old boy with cavernous sinus thrombosis and right internal carotid
      artery narrowing without neurological sequelae, right subdural empyema, and
      cerebritis in the right temporal and occipital lobes. Neuroimaging also
      demonstrated right jugular vein thrombosis. Cultures of samples from the blood
      proved positive for the presence of Fusobacterium necrophorum. The patient
      underwent unilateral tonsillectomy, drainage of the peritonsillar abscess, and a
      myringotomy on the right side. Postoperatively the patient was treated
      conservatively with antibiotic therapy resulting in an excellent outcome.

PMID- 17233315
TI  - Epidural hematoma formation following trivial head trauma in a child with
      osteogenesis imperfecta. Case report.
AB  - Osteogenesis imperfecta (OI) represents a rare heterogeneous group of inherited
      disorders characterized by low bone mass, increased bone fragility, and other
      connective tissue manifestations. This condition can contribute to dramatic
      complications after a seemingly insignificant injury. A large epidural hematoma
      that developed in a child with OI after a trivial fall highlights the importance
      of close monitoring in these patients. After an injury that occurred several
      months prior to the head trauma the authors describe, this child had been placed
      in foster care because it was believed that his skeletal injuries were caused by
      nonaccidental injury. Subsequent genetic analysis confirmed that the child was
      heterozygous for the missense mutation c767G>T,pG256V at exon 16 of COLIA2,
      consistent with OI, and the foster care order was overturned. The authors review
      the literature concerning OI, its relationship to head injury, and the importance
      of genetic analysis in its diagnosis.

PMID- 17233316
TI  - Medulloblastoma arising from an immature teratoma of the posterior fossa. Case
      report.
AB  - Teratomas, a group of nongerminomatous germ cell tumors, account for 3% of all
      childhood tumors. These unusual lesions reproduce the cellular and structural
      phenotypic traits associated with the three classic germ layers in inappropriate
      places in the body and often retain an embryonal character. These immature cells
      can differentiate into more malignant neoplasms. An intracranial location for
      this lesion type is rare. The authors describe the case of a 2-year-old boy with
      a teratoma of the posterior fossa that had partially differentiated into a
      medulloblastoma.

PMID- 17233317
TI  - Benign fibrous histiocytoma of the skull base. Case report.
AB  - The authors report the case of benign fibrous histiocytoma (BFH) of the skull
      base in an 11-month-old girl. During draining for a middle ear infection, the
      child was noted to have an anomalous mass in the skull base. On magnetic
      resonance imaging studies a soft-tissue mass of the skull base primarily
      involving the regions of the temporal and occipital bones was discovered. Results
      of a surgical biopsy were consistent with BFH. At the most recent follow-up
      examination--18 months postoperatively--the child was noted to be asymptomatic
      with no gross increase in tumor size.

PMID- 17233318
TI  - Transfemoral vein placement of a ventriculoatrial shunt. Technical note.
AB  - Acceptable cavities for the distal portion of a cerebrospinal fluid diversion
      shunt include the peritoneal, pleural, and atrial cavities. The authors report on
      a patient in whom placement into the peritoneal cavity failed, the pleural cavity
      was not an option, and access to the right atrium was not technically possible
      via standard cannulation techniques into the veins of the neck and shoulder
      regions. A right ventriculoatrial shunt was thus placed into the right atrium via
      the ipsilateral femoral vein. Eight months postoperatively, the patient's
      condition was at baseline and there were no signs of shunt malfunction. This
      technique may prove useful when other measures have failed.

PMID- 17233319
TI  - Cranial trephination in ancient Iran. Case illustration.

PMID- 17233320
TI  - A historical case of beaten-copper cranium.
AB  - The authors present the oldest historical case of a so-called beaten-copper
      cranium. The typical pattern was identified on a skull from a child, probably a
      boy, who died at approximately 6 years of age and was buried in a provisional
      cemetery used during the siege of Hanau, Germany, in 1635 and 1636. Morphological
      and radiological analyses of the severe digitate impressions ubiquitous on the
      child's endocranium support the diagnosis of chronically elevated intracranial
      pressure due to hydrocephalus.

PMID- 17233321
TI  - Chiari malformation.

PMID- 17233322
TI  - Randomized clinical study on the efficacy of a new lacquer for dentine
      hypersensitivity.
AB  - The purpose of this randomized, clinical, double-blind short-term trial was to
      evaluate the efficacy of a new lacquer containing a new component (phosphonic
      acid methacrylate) designed for treating dentine hypersensitivity. Eighty-eight
      patients participated in this study. At the first visit one tooth was treated
      with the lacquer (1), while another tooth was treated with a placebo (2).
      Sensitivity levels were determined before treatment as well as after one week. An
      air blast stimulus and a visual analogue scale were used for evaluation. At
      baseline, the mean hypersensitivity score of group 1 (53.2+/-26.3) was comparable
      to the mean hypersensitivity score of the teeth in group 2 (53.3+/-24.4). After
      one week, a significant reduction of the mean hypersensitivity scores (p <0.001;
      t-test) was revealed in group 1 (25.8 +/-26.6) as well as in group 2 (26.4+/
      25.3). The difference between the two treatment groups was not significant (p =
      0.7). There is either no difference between the two treatment modalities or the
      placebo response and/or the time effect was so strong that the treatment efficacy
      of the new lacquer was hidden by these effects.

PMID- 17233323
TI  - [Micro Apical Placement System (MAPS) . A new instrument for retrograde root
      filling].
AB  - A retrograde radicular preparation in the axis of the root canal as well as an
      excess-free obturation of the canal is surgically very demanding due to the
      complex anatomical structures and to the limited intraoral operative field. As
      from the early 1990s, advisable methods for the retrograde root canal obturation
      under minimal place requirements have been implemented thanks to ultrasonic- and
      sonic-driven microinstruments. This publication presents a new microsurgical
      instrument, the "Surgical-Retro" Micro Apical Placement System (MAPS), which
      facilitates in a large extent the retrograde obturation with a plas tic root
      canal filling material. The device provides an unrestricted access to the
      retrograde cavity, allowing thus an accurate obturating technique whilst avoiding
      the dispersion of the root canal filling material in the surrounding bone. Thanks
      to the "Surgical-Retro" Micro Apical Placement System, a further gap in the
      improvement of the quality and, thus, of the success of the treatment by apical
      resection has been filled.

PMID- 17233324
TI  - [Tobacco-associated lesions of the oral mucosa].
AB  - Consumption of tobacco can result not only in a multitude of different general
      health problems like carcinoma of the lung, ischaemic cardiac diseases,
      peripheral vascular diseases, stroke, chronic-obstructive pulmonary diseases or
      peptic ulcers, but also in pathologic lesions of the oral mucosa. Benign oral
      lesions from smoking or consumption of smokeless tobacco are the so-called
      smoker's palate and smoker's melanosis. On the other hand, tobacco-associated
      lesions like oral leukoplakia or oral squamous cell carcinoma are already
      potentially life-threatening diseases that in general require active treatment.
      The following review article will present and discuss the typical lesions of the
      oral mucosa that result from chronic tobacco consumption. The aim of this article
      is to demonstrate dental health care providers the needs and benefits of tobacco
      use cessation in a dental setting, especially regarding stomatologic sequelae and
      consequences. The present article is the first in a series of articles from the
      Swiss task force "Smoking - Intervention in the private dental office" on the
      topic "tobacco use and dental medicine".

PMID- 17233325
TI  - The effect of Swedish and American smokeless tobacco extract on periodontal
      ligament fibroblasts in vitro.
AB  - Use of moist snuff is widespread in Sweden. In 2004 approximately 8oo,ooo Swedes
      were daily users which corresponds to 22% of the male population and 3% of the
      female population. The aim of the present study was to evaluate the effect of
      Swedish moist snuff extract on PDLfibroblast growth and hard tissue production
      and compare with moist snuff extract from USA. Periodontal ligament cells (PDL
      cells) were obtained from 3 healthy subjects (1 female 14 years, 2 males 14 and
      17 years) from the root surface of premolars extracted for orthodontic reasons.
      The cells were isolated from explants and grown in Dulbecco's Modified Eagle's
      Medium (DMEM) supplemented with 10% fetal calf serum (FBS) and cultivated in 37
      degrees C with 5% CO2 in air. Snuff extract in concentrations 0.3%, 1% and 3% (in
      DMEM with 1% FBS) was tested. Cells from each individual were tested three times,
      each time in triplicate. Photographs were taken at o and 24 hours with a digital
      camera and analysed in terms of growth and morphology. Then the cell suspension
      was frozen and later thawed for examination of the production of alkaline
      phosphatase after exposure to different snuff concentrations. This in vitro study
      has shown that PDL cells from 3 different subjects demonstrated a reduced number
      of cells at exposure to 3% of both Swedish and American snuff extract. The
      production of alkaline phosphatase after 2 hours was similarly reduced from cells
      exposed to 3% snuff extract. Further studies have to be made to understand the
      effect of smokeless tobacco on periodontal tissues. However, from this study can
      be concluded that smokeless tobacco has biological effects in terms of reduced
      PDL cell growth and production of alkaline phosphatase

PMID- 17233326
TI  - Cost of composite and glass ionomer class II molar restorations and theoretical
      analyses of cost per year of function at public dental services in Sweden.
AB  - The aim was to evaluate the cost of direct composite and glass ionomer class II
      molar restorations, and the theoretical cost per year of function, at Public
      Dental Services (PDS) in Sweden, years 2000 and 2005. Costs for patients, Social
      Insurance Offices (SI; Forsakringskassan), and total cost, were calculated based
      on fee schedules from all PDS in Sweden. Theoretical cost per year calculations
      were based on the median survival times (MST) of failed direct composite and
      glass ionomer class II molar restorations, derived from a set of clinical studies
      conducted in Nordic general practices. Due to lack of national statistics from
      SI, the number of direct restorations including more than one surface, made in
      adults, in general dentistry at PDS in the county of Halland were studied. From
      the year 2000 to year 2005, the total cost of composite class II molar
      restorations increased by 25%, whereas the total cost of glass ionomer
      restorations more than doubled. Theoretical calculations implied a higher cost
      per year of function for composite restorations in year 2000, whereas in year
      2005, glass ionomer restorations had a higher cost per year of function. The cost
      of direct composite and glass ionomer class II molar restorations increased from
      year 2000 to 2005, at PDS in Sweden. In the context of planning public health
      care funding, theoretical models for cost prediction may prove useful.

PMID- 17233327
TI  - Oral health and treatment need among older individuals living in nursing homes in
      Skaraborg, Vastra Gotaland, Sweden.
AB  - The aim of this study was to describe the oral health among residents living in
      seven nursing homes in Skaraborg,Vastra Gotaland, Sweden. The study was cross
      sectional and included two parts; a clinical examination and a patient
      questionnaire. To be included in the study, each subject should be able to
      understand and answer simple questions about their general and oral health, and
      also be able to participate in a clinical examination. In all, 172 individuals
      were included in the study sample. Edentulousness was prevalent, and more than
      50% of the subjects were edentulous in the maxilla. Poor denture stability and
      retention were observed among the majority of the edentulous subjects, while
      fractured/decayed teeth and remaining roots were common among the dentate
      subjects. 47% had oral mucosal lesions. Mucosa friction index was high, and good
      oral hygie ne was registered for 12% of the dentate subjects. The majority of the
      patients with remaining teeth brushed their teeth twice a day, while those
      wearing dentures brushed more seldom. The majority of the respondents claimed,
      they had not received help from the program included in the Swedish National
      Dental Insurance System, introduced in 1999. The intention with the program was
      to promote good oral health among individuals, who due to medical--or social
      conditions, were not able to attend the regular oral health care system.

PMID- 17233328
TI  - Quality managements and work environment in oral and maxillofacial surgery in
      Sweden.
AB  - The aim of this study was to investigate if the Oral and Maxillofacial Surgery
      (OMFS) clinics in Sweden actively work with quality development and if so, which
      systems they use. A further aim was to explore the opinion of the employees about
      quality work. Data were collected by way of a questionnaire with 67 questions,
      related to quality management at the clinic and to the content of healthy work.
      22 clinics with 297 employees responded, 65% of the clinics and 86% of the
      employees. More than half of the respondents stated that they worked with a
      management system, but there was uncertainty as to the type of a quality system.
      Only at two clinics, all the respondents agreed on the system. This showed that
      one of the most important aspects in a quality system, i.e. to inform everyone,
      was unsatisfactory. The study showed that dental nurses and assistant nurses were
      more appreciative of quality as a tool for improvement than the maxillo-facial
      surgeons. There was no such difference concerning the importance of quality work.
      Dental nurses thought that the quality was more important for the working
      situation concerning the physical environment than did the maxillo-facial
      surgeons.

PMID- 17233329
TI  - Interocclusal appliances--indications and clinical routines in general dental
      practice in Sweden.
AB  - The aim of this study was to analyse what kind of interocclusal appliances that
      are used in general dental practice in Sweden, the indications for such
      treatment, to what extent a clinical status is recorded before treatment, as well
      as the routines for evaluation of treatment results. The study was a
      retrospective analysis of patient records from 320 adult patients who had been
      treated by general dental practitioners in the Public Dental Service in Sweden.
      For comparison a group of 88 consecutive patients who had received interocclusal
      appliance therapy at a specialist clinic was used. The most common indication for
      treatment with hard acrylic stabilisation appliances, as well as with soft
      appliances, was occlusal wear due to tooth grinding. The second most common
      indication for treatment with hard acrylic stabilisation appliances was pain from
      masticatory muscles, while the second most common indication for soft appliances
      was tension-type headache. Treatment with soft appliances was more often combined
      with other treatment modalities compared to treatment with hard acrylic
      stabilisation appliances. Large variations were found between the 3 general
      dental clinics and the specialist clinic in respect of treatment indications,
      combinations with other treatment modalities, recording of clinical findings,
      follow-ups and evaluation of treatment results. General conclusion should,
      however, be made with caution due to the risk of selection bias. From the results
      of this study it is obvious that treatment with soft appliances is common in
      general dental practice in Sweden, despite the lack of scientific support for
      their efficacy, as well as effectiveness, compared to hard acrylic stabilisation
      appliances. There is an obvious need for investigations of the decision-making
      processes among dentists when performing treatment with interocclusal appliances,
      as well as for randomised controlled studies concerning efficacy and
      effectiveness of soft appliances.

PMID- 17233330
TI  - [Not Available].

PMID- 17233331
TI  - [Not Available].

PMID- 17233332
TI  - [Not Available].

PMID- 17233333
TI  - [Not Available].

PMID- 17233335
TI  - [Not Available].

PMID- 17233334
TI  - [Not Available].

PMID- 17233336
TI  - [Not Available].

PMID- 17233338
TI  - [Not Available].

PMID- 17233337
TI  - [Not Available].

PMID- 17233339
TI  - [Not Available].

PMID- 17233340
TI  - [Not Available].

PMID- 17233341
TI  - [Not Available].

PMID- 17233343
TI  - [Not Available].

PMID- 17233342
TI  - [Not Available].

PMID- 17233344
TI  - [Not Available].

PMID- 17233345
TI  - [Not Available].

PMID- 17233346
TI  - [Not Available].

PMID- 17233347
TI  - [Not Available].

PMID- 17233348
TI  - [Not Available].

PMID- 17233349
TI  - [Not Available].

PMID- 17233350
TI  - [Not Available].

PMID- 17233351
TI  - [Not Available].

PMID- 17233352
TI  - [Not Available].

PMID- 17233353
TI  - [Not Available].

PMID- 17233354
TI  - [Not Available].

PMID- 17233355
TI  - [Not Available].

PMID- 17233356
TI  - [Not Available].

PMID- 17233357
TI  - [Not Available].

PMID- 17233358
TI  - [Not Available].

PMID- 17233359
TI  - [Not Available].

PMID- 17233360
TI  - [Not Available].

PMID- 17233361
TI  - Which serves best in monitoring arousal response to tracheal intubation?
      Bispectral index, sprectral entropy or AEP?

PMID- 17233362
TI  - Serial changes of pulse wave velocity and correlations with hemodynamic
      parameters during general anesthesia.
AB  - BACKGROUND: Increased pulse wave velocity (PWV) is a marker of increased arterial
      stiffness and is correlated with cardiovascular mortality and mortality of all
      causes in the elderly and in patients with essential hypertension and type 2
      diabetes. There is also a positive correlation between PWV and arterial blood
      pressure. The changes of PWV in response to general anesthesia and surgical
      stimulation remain unclear. The aim of this study was to continuously monitor the
      PWV, blood pressure and heart rate, and to assess their correlations during
      general anesthesia in women receiving gynecologic surgery. METHODS: The values of
      PWV were obtained from calculation of the finger-to-toe distance divided by the
      transit time using dual-channel photoplethysmography system. The values of PWV,
      systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were
      recorded before anesthesia induction, 5 min before incision, at incision, in
      continuation for at least 30 min thereafter, and 5 min after discontinuation of
      sevoflurane. The correlations between PWV and SBP, DBP and heart rate during the
      general anesthesia were analyzed using Pearson's correlation test. RESULTS: The
      serial records of PWV and hemodynamic parameters showed that PWV, SBP, DBP, and
      heart rate decreased after induction of anesthesia. SBP and DBP increased after
      surgical incision. There was a trend of progressively declining of PWV and DBP
      during the general anesthesia but SBP and heart rate remained stationary. All the
      values of PWV, SBP, DBP, and heart rate increased after discontinuation of
      anesthesia. There were significant correlations between PWV and SBP (r = 0.4558,
      P < 0.0001), between PWV and DBP (r = 0.2719, P < 0.0001), between PWV and pulse
      pressure (r = 0.2067, P < 0.0001), and between PWV and mean arterial pressure (r
      = 0.3969, P < 0.0001). CONCLUSIONS: We could evaluate the serial changes of PWV
      in response to general anesthesia and surgical stimulation using a simple and
      noninvasive dual-channel photoplethysmography system. The value of PWV, an index
      of arterial stiffness, has significant correlation with arterial blood pressure.

PMID- 17233364
TI  - Utility of the auditory evoked potentials index as an indicator for endotracheal
      intubation.
AB  - BACKGROUND: The A-line ARX Index (AAI) has been used as an indicator of depth of
      anesthesia. The study examined whether AAI-guided endotracheal intubation (EI),
      compared with experience guidance, could provide better hemodynamic stability
      during general anesthesia (GA). METHODS: One hundred and four patients were
      included in this study. In the control group, EI was performed based on the
      judgment of the anesthesiologist by clinical experience. In the study groups, EI
      was performed at an AAI value of either 15, 20, or 30. GA was induced with
      cisatracurium, lidocaine, fentanyl, thiamylal and succinylcholine. Heart rate
      (HR) and mean arterial pressure (MAP) were recorded at baseline, 1 min before and
      1 and 3 min after intubation. The change of hemodynamics over 20% in the space
      between 1 min before and after intubation was defined as severe change. RESULTS:
      The incidences of severe changes of HR and MAP in the AAI-15 and AAI-20 groups
      were significantly lower than those in the control group (19% and 39% vs. 68%, P
      < 0.01 and 0.05; 52% and 52% vs. 91%, P < 0.01, respectively). The induction time
      was significantly shorter in the control group than that in the study groups (183
      +/- 47 vs. 366 +/- 151, 248 +/- 53, and 255 +/- 85 sec, P < 0.01). Highest dose
      of thiamylal and longest induction time were needed in the AAI-15 group.
      CONCLUSIONS: Compared with the routine clinical practice, AAI monitoring helps to
      achieve better condition for EI during induction with less hemodynamic changes.
      The AAI value of 20 is suggested as an optimal indicator for EI.

PMID- 17233363
TI  - Urinary catheterization may not be necessary in minor surgery under spinal
      anesthesia with long-acting local anesthetics.
AB  - BACKGROUND: This prospective study was designed to compare the incidence of
      urinary retention after spinal anesthesia between 0.5% hyperbaric bupivacaine and
      0.5% hyperbaric tetracaine in patients who underwent minor orthopedic and general
      surgeries. METHODS: Eighty patients aged 18-40 were randomly assigned to receive
      either hyperbaric bupivacaine or tetracaine for spinal anesthesia. Intravenous
      fluids were administered for maintenance of basal requirement, replacement of
      blood loss and prevention of hypotension. The highest level of analgesia,
      regression time of sensory block to L5 level, length of time from spinal
      injection to spontaneous urinary voidance, and volume of perioperative fluid
      administered were recorded. RESULTS: Of the 80 patients who received either
      hernioplasty, fistulectomy, hemorroidectomy or orthopedic surgery, two were
      catheterized (2.5%) because of urinary retention. They were administered less
      than 800 mL of fluid intraoperatively. Intraoperative blood loss was less than
      100 mL in all cases. There were no statistical differences in demographic data,
      types of surgery, sensory blockade and perioperative fluid administration between
      the two groups. Although the regression time of sensory blockade with tetracaine
      (means +/- SD, 259.3 +/- 39.6 min) was significantly longer than that of
      bupivacaine (225.0 +/- 38.6 min, P < 0.01), the time elapsing from the spinal
      injection to the first spontaneously voiding after surgery did not show
      statistical difference between two groups (433.9 +/- 89.1 vs. 411.0 +/- 98.3 min,
      P = 0.286). CONCLUSIONS: Our results show that, in younger surgical patients who
      did not receive large amount of fluid intraoperatively, the incidence of urinary
      retention was low, although prolonged sensory blockade by both long-acting local
      anesthetics was evident. Thus, urinary catheterization should not be a routine
      must for every patient undergoing minor surgery with long-acting spinal local
      anesthetics. From the viewpoint of financial expense, avoidance of complication
      and annoyance of urinary catheterization, careful observation of urinary bladder
      fullness in the form of lower abdominal distension, discomfort, bradycardia, or
      vomiting after surgery is superior to routine retention urinary catheterization
      just for ease with work in younger patients under-going minor surgery under long
      acting spinal local anesthetics.

PMID- 17233365
TI  - Effect of oral ketamine on the postoperative pain and analgesic requirement
      following orthopedic surgery.
AB  - BACKGROUND: Ketamine is a potent analgesic agent in addition to its anesthetic
      properties. Oral ketamine has been used to treat postoperative stump pain
      following lower limb amputation. In this study, oral ketamine was used to reduce
      the severity of postoperative pain following orthopedic surgery. METHODS: Seventy
      two adult traumatic patients undergoing orthopedic operations were randomly
      divided into ketamine and placebo groups. In ketamine group, oral ketamine
      administered at 8-hour intervals postoperatively. Severity of postoperative pain,
      amount of morphine used, and the time to first rescue analgesic were determined
      and compared between two groups. RESULTS: Patients in ketamine group had
      significantly lower scores of postoperative pain (5.2 +/- 1.2, 4.9 +/- 1.6, 4.4
      +/- 2.2, 4.3 +/- 1.5, and 3.4 +/- 1.3 at 2, 4, 8, 16, and 24 h postoperatively
      vs. 7.7 +/- 1.5, 7.3 +/- 1.6, 6.3 +/- 1.9, 6.0 +/- 1.6, and 5.1 +/- 1.8 in
      placebo group; P < 0.05). The amount of morphine required in the first
      postoperative day was significantly lower in ketamine group (10.1 +/- 5.6 mg vs.
      13.4 +/- 7.8 mg in placebo group; P < 0.05). Time to first rescue analgesic in
      the ward was significantly longer in ketamine group (3.5 +/- 1.5 h vs. 1.9 +/-
      1.2 h in placebo group; P < 0.05). A female patient in ketamine group developed
      postoperative emergence reaction following extubation. CONCLUSIONS: Oral ketamine
      may be used to reduce postoperative pain following orthopedic procedures in the
      traumatic patients. Since only one patient developed psychological side effect
      (which we can not attribute to ketamine with certainty) it can be concluded that
      oral ketamine is not so fearsome with respect to emergence reaction.

PMID- 17233366
TI  - Management of catheter-induced pulmonary artery perforation during weaning from
      cardiopulmonary bypass--a case report.
AB  - We report a case of pulmonary artery perforation induced by Swan-Ganz catheter.
      Brisk massive airway hemorrhage occurred after withdrawl of the Swan-Ganz
      catheter post cardiopulmonary bypass. Early recognition, immediate re
      establishment of cardiopulmonary bypass, lobectomy of the sanguineous lobe
      subsequent to rupture of the involved pulmonary artery, and thorough bronchial
      toilet were the major determinants contributing to successfully rescuing the
      patient's life. She was discharged uneventfully in spite of high mortality rate
      of the catheter-induced pulmonary artery perforation.

PMID- 17233367
TI  - Fiberoptic tracheal intubation through a classicial laryngeal mask airway under
      spontaneous ventilation in a child with Treacher Collins syndrome.
AB  - This report cites the usefulness of fiberoptic scope-guided endotracheal tube
      intubation through a classical laryngeal mask airway (LMA) during spontaneous
      breathing. Treacher Collins Syndrome (TCS) is a condition where airway management
      is stressful to anesthesiologists. We report a pediatric patient with TCS
      undergoing cleft palate repair. The patient had a history of sleep apnea
      syndrome, chronic lung disease, and congenital heart disease. Intubation by rigid
      laryngoscopy was unsuccessful at the first attempt. One month later, under
      spontaneous ventilation, tracheal intubation was smoothly performed with the use
      of a fiberoptic scope through an LMA under intravenous anesthesia with propofol.
      Fiberoptic scope-guided endotracheal intubation through an LMA with the push of
      another ETT of the same size to curb the back slippage of the endotracheal tube
      already inserted in the trachea can be easily and safely performed under
      spontaneous breathing in a pediatric patient with TCS.

PMID- 17233368
TI  - Management of postdural puncture headache by epidural saline delivered with a
      patient-controlled pump--a case report.
AB  - Unintentional dural puncture is the most frequent cause of postdural puncture
      headache (PDPH) in epidural anesthesia and analgesia. Conservative treatments of
      PDPH include bed rest, oral analgesics, and hydration. When conservative measures
      fail, epidural blood patch is an effective substitute. However, epidural blood
      patch carries some risks, such as subdural hematoma, pneumocephalus, exacerbation
      of PDPH and new dural puncture. Many patients may refuse the procedure due to the
      risks involved. We describe a female patient who had her PDPH successfully
      treated with epidural saline delivered by a patient-controlled analgesia device
      (Abbott Pain Management-APM) without molestation of her daily activities.

PMID- 17233369
TI  - Intraoperative pneumothorax during laparoscopic cholecystectomy.
AB  - Anesthesiologists currently view laparoscopic cholecystectomy resemblant to other
      laparoscopic procedures with respect to the necessity of inducing a
      pneumoperitoneum via abdominal insufflation of carbon dioxide (CO2). The present
      case report describes a healthy 63-year-old man who while undergoing elective
      laparoscopic cholecystectomy under general anesthesia, developed hypoxemia in the
      course in consequence of pneumothorax. This complication, although rare, can be
      catastrophic if prompt diagnosis and rapid intervention and management do not
      come in the nick of time.

PMID- 17233370
TI  - Myocardial infarction masked by high level spinal anesthesia in a patient
      undergoing herniorrhaphy.
AB  - Myocardial infarction (MI) is one of the leading causes of perioperative
      morbidity. Although evidence to prove significant reduction of perioperative MI
      with regional anesthesia is lacking, anesthesiologists still prefer this
      technique over general anesthesia for surgery involving the lower abdomen or
      lower extremities, especially in patients with cardiac risks. However, high level
      of sensory block during spinal anesthesia may obscure the referred pain from MI,
      which could contribute to the delay of diagnosis and treatment of an acute
      perioperative attack. We report a case of MI which occurred either
      intraoperatively or postoperatively, with symptoms that were masked by high level
      of sensory block to T4 by spinal anesthesia. This perioperative MI was only
      diagnosed when the patient recovered from anesthesia in the post-anesthesia care
      unit (PACU).

PMID- 17233371
TI  - Intravenous propofol precipitates the hypotension induced by inadvertent epidural
      thiopental injection.
AB  - Administration of improper drugs into epidural space is occasionally present in
      anesthetic practice. In most instances it would not contribute to significant
      neurological complications. There had not been severe hypotension reported in the
      literature in consequence of inadvertent epidural thiopental administration. Here
      we describe our experience in a case of inadvertent epidural administration of
      thiopental coinciding with induction of anesthesia with propofol, as a
      consequence of which profound hypotension was induced, necessitating aggressive
      inotropic and vasopressive agents to maintain blood pressure. Rapid vascular
      uptake of thiopental in the epidural space and synergistic action of propofol
      jointly contributed to the development of the hypotension. Attempts to forestall
      neurological sequela after the inadvertence seem unnecessary unless apparent
      symptoms or signs of neurological injury have come upon.

PMID- 17233372
TI  - Intramyometrial injection of vasopressin causes bradycardia and cardiac arrest-
      report of two cases.
AB  - Vasopressin has been documented to effectively reduce blood loss in gynecologic
      practice. However, local infiltration of vasopressin may cause lethal
      cardiopulmonary complications in spite of rarity of reported cases. Severe
      bradycardia and cardiac arrest were encountered after intramyometrial injection
      of vasopressin in our two healthy patients undergoing open uterine myomectomy. We
      herewith discuss the associated complications and the anesthetic considerations.

PMID- 17233373
TI  - It's time to end forced treatment.

PMID- 17233374
TI  - Addressing a national tragedy.

PMID- 17233375
TI  - Betting on better access to care.

PMID- 17233376
TI  - Investing in frontline workers.

PMID- 17233377
TI  - A multidisciplinary approach.

PMID- 17233378
TI  - Decision support is in its infancy.

PMID- 17233379
TI  - Recovery: the bridge to integration? Part two.

PMID- 17233380
TI  - Managing the risk of tardive dyskinesia.

PMID- 17233381
TI  - Refocusing on behavior and wellness.

PMID- 17233382
TI  - Mapping a better strategy.

PMID- 17233383
TI  - What it takes to work together.

PMID- 17233384
TI  - Remembering Wayne Fenton.

PMID- 17233385
TI  - [Evaluation of FDG-PET imaging for the detection of gastrointestinal tract cancer
      in patients with suspected lung cancer].
AB  - This study evaluated 18F-FDG-PET imaging for the detection of gastrointestinal
      tract cancer in patients with suspected lung cancer. A total of 351 patients who
      had abnormal lung shadows and who underwent whole-body FDG-PET between June 1998
      and January 2006 were retrospectively entered for analysis. Gastrointestinal
      tract cancers were subsequently found in 15 patients (4.3%) who had been found to
      have lung diseases consisting of 7 inflammatory changes, 6 lung cancers, and 2
      metastatic lung carcinomas, 9 colon cancers, 4 gastric cancers, and 2 esophageal
      cancers. Five patients (2 colon cancers, 2 gastric cancers, and 1 esophageal
      cancer) had early stage carcinoma. In this study, FDG-PET was useful not only for
      the diagnosis and staging of lung cancer, but also for the detection of
      unexpected gastrointestinal tract cancers. FDG-PET may be most suitable for
      cancer screening.

PMID- 17233386
TI  - [Etiology and outcome of community-acquired pneumonia in relation to age and
      severity in hospitalized adult patients].
AB  - The aim of this study was to determine the etiology and outcome of community
      acquired pneumonia (CAP) in relation to age and severity in hospitalized
      patients. Overall, 652 consecutive patients with CAP were studied retrospectively
      during a 4-year period from 2002. Severity of pneumonia was classified according
      to the guidelines of the Japanese Respiratory Society (JRS 2005) and American
      Thoracic Society (ATS 2001). The etiology was identified in 401 of 652 (61.5%)
      cases. The four most frequent pathogens were Streptococcus pneumoniae (26.2%),
      influenza virus (12.4%), Mycoplasma pneumoniae (10.9%), and Haemophilus
      influenzae (5.9%). The most common pathogen in the younger (15-44 years) group
      and very severe patients (JRS) was Mycoplasma pneumoniae (38.4%) and influenza
      virus (28.6%), respectively. The three most frequent pathogens in severe CAP
      patients (ATS) were Streptococcus pneumoniae (29.0%), influenza virus (17.4%),
      and Legionella species (13.0%). The overall mortality was 6.4%. The mortality of
      CAP patients among aged 1544, 45-64, 65-74, and 75 years or older was 1.4%, 3.3%,
      6.9% and 9.3%, respectively. The mortality of mild, moderate, severe, and very
      severe patients (RS) was 0%, 4.1%, 15.5%, and 53.6%, respectively. The mortality
      of non-severe and severe patients (ATS) was 1.8% and 23.9%, respectively. Age and
      severity had influence on the prevalence of the main microbial pathogens.
      Streptococcus pneumoniae remained the most important pathogen that needs
      consideration in initial antibiotic therapy in patients with CAP of all ages and
      severities. Pathogens identified in patients with severe CAP in Japan were
      similar to those of Western countries, except for the high incidence of the
      influenza virus.

PMID- 17233387
TI  - [Predicted vales of respiratory function tests in young Japanese aged from 10 to
      20 years].
AB  - To find predicted values of respiratory function tests in young persons in Japan,
      we measured slow vital capacity and forced vital capacity in 1,141 subjects aged
      from 10 to 20 years. The values obtained from 636 persons (363 males and 273
      females) who were not smokers or had no suspected rhinitis or asthma were
      analyzed. Although FEV1% by the Gaensler and Tiffeneau methods were almost
      constant regardless of age, all other values of respiratory function tests
      increased with age and then reached a plateau level in late teens. Excluding the
      Gaensler and Tiffeneau FEV1%, in a single regression analysis using gender, age,
      and height, both the contribution ratio and regression coefficient were the
      highest using height, followed by age. In addition, the result was similar with
      multiple regression analysis. Therefore, for a young person aged from 10 to 20
      years, body height is the most important predictor variable of respiratory
      function tests, compared to gender and age. For each respiratory function test,
      we showed the prediction relation according to gender obtained from multiple
      linear regression analysis using 2 variables of height and age.

PMID- 17233388
TI  - [A case of intravascular lymphomatosis with no abnormal findings on chest
      computed tomography and with diffuse pulmonary uptake of 67Ga on scintigraphy].
AB  - A 45-year-old man was admitted to our hospital with high-grade fever uncontrolled
      by antipyretic drugs, and elevation of the serum LDH and sIL-2R levels, and
      decrease of diffusing capacity for carbon monoxide. Chest computed tomography
      (CT) showed no abnormal findings but 67Ga scintigraphy revealed diffuse pulmonary
      uptake. He was given a diagnosis of intravascular lymphomatosis (IVL) based on
      transbronchial lung biopsy (TBLB) and immunohistochemical analysis. The prognosis
      of IVL is generally bad, because antemortem diagnosis is difficult. In this case
      early TBLB enabled satisfactory curative effect of IVL.

PMID- 17233389
TI  - [A case of salazosulfapyridine-induced pneumonitis presenting with multiple
      pulmonary nodules and lymphadenopathy].
AB  - We report a rare case of drug-induced pneumonitis, probably caused by
      salazosulfapyridine, showing a radiographic pattern of multiple pulmonary nodules
      and lymphadenopathy. An 18-year-old woman was admitted to our hospital because of
      fever, skin rash, dry cough and dyspnea on exertion. She had been given
      salazosulfapyridine for two weeks to treat Crohn's disease. A chest radiograph
      and computed tomographic scan showed multiple nodular shadows in both lung
      fields, mediastinal lymphadenopathy, and bilateral pleural effusions. Cessation
      of salazosulfapyridine followed by corticosteroid therapy led to an immediate
      symptomatic improvement. The drug-induced lymphocyte stimulation test for
      salazosulfapyridine was negative. The same symptoms reappeared with rechallenge
      of SASP, however, which led to diagnosis as salazosulfapyridine-induced
      pneumonitis. This is apparently the first case report of salazosulfapyridine
      induced pneumonitis with a radiographic pattern of multiple pulmonary nodules;
      accumulation of similar case reports are needed to confirm the association.

PMID- 17233390
TI  - [A case of myelodysplastic syndrome complicated with organizing pneumonia].
AB  - A 74-year-old man had been given a diagnosis of myelodysplastic syndrome (MDS),
      and had been treated with granulocyte-colony stimulating factor (G-CSF). 1 year
      later, he suffered from fever and his chest X-ray lung biopsy did not provide a
      diagnosis, video-assisted thoracoscopic lung biopsy was performed, which yielded
      a histological diagnosis of organizing pneumonia. His pulmonary disease was
      diagnosed as secondary organizing pneumonia due to MDS, and was treated
      successfully with steroids. Vigorous efforts to establish a histological
      diagnosis is needed for the antibiotics-resistant pneumonia in the case of MDS.

PMID- 17233391
TI  - [A case of polymyositis with concomitant diffuse alveolar damage following
      interstitial pneumonia].
AB  - A 68-year-old woman had been given a diagnosis of interstitial pneumonia (NSIP
      pattern) and followed up at our hospital for 3 years. She was admitted to our
      hospital because of dyspnea, lower limb edema and myalgia. On admission, serum
      CPK and CRP levels were elevated and an electromyogram suggested inflammatory
      myopathy. We diagnosed polymyositis (PM) with progressive interstitial pneumonia
      (IP). Although methylprednisolone pulse therapy and immunosuppressive agents were
      administered, pulmonary lesions became aggravated. The patient died due to
      respiratory failure as a result of the progress of IP. The autopsy lung revealed
      diffuse alveolar damage (DAD) at the both acute and fibrotic phases, suggesting
      that DAD could coincide with PM. We report here a rare case of polymyositis with
      diffuse alveolar damage (DAD).

PMID- 17233392
TI  - [A case of CD56 positive T-cell lymphoma originating from mediastinal lymph
      nodes].
AB  - The patient, a 63-year-old man was admitted to our hospital with complaints of
      high-grade fever and left chest pain. The chest X-ray film taken on admission
      showed the presence of pleural effusion. The chest CT scan revealed left
      mediastinal enlargement. Examination of the pleural effusion showed a high
      concentration of adenosine deaminase (ADA) and the cytological examination showed
      no malignancy. We diagnosed pleuritis tuberculosa. His general condition worsened
      in spite of anti-tuberculosis therapy and soluble interleukin-2 receptor (sIL-2R)
      was elevated. The video-assisted thoracoscopic biopsy was negative. Soon after
      that the lymph nodes from the left supraclavicular region to the mediastinum
      became swollen. The diagnosis of peripheral T-cell lymphoma, unspecified (WHO
      classification) with CD56 expression, was established based on the results of
      lymph node biopsy and pleural effusion cytology. He was treated with
      cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy. Since
      two courses of chemotherapy were not effective we changed to
      carboplatin/ifosfamide/ etoposide/dexamethasone (DeVIC) chemotherapy. His
      condition improved and a complete response was obtained. In conclusion, the
      presence of a high level of ADA in the pleural effusion and resistance to anti
      tuberculosis therapy should suggest a malignant lymphoma.

PMID- 17233393
TI  - [A case of drug-induced pneumonitis due to levofloxacin and kampo medicine].
AB  - A 55-year-old woman was admitted to our hospital because of dyspnea on exertion.
      Hypoxemia and restrictive ventilatory impairment were observed on admission.
      Chest radiographs showed diffuse patchy infiltration shadows in both lungs. We
      suspected drug-induced pneumonitis, because her history of fever seemed to be
      related to drug administration for sinusitis. Her symptoms and findings were
      gradually decreased by discontinuation of the drugs. Transbronchial lung biopsy
      specimens showed lymphocyte dominant infiltration in the alveolar septa and
      Masson bodies. Drug lymphocyte stimulation tests were positive for levofloxacin
      and shin-i-seihai-to, a kampo medicine. On the basis of these findings, we
      arrived at a diagnosis of drug-induced pneumonitis caused by these drugs.

PMID- 17233394
TI  - [A case of acute pulmonary thromboembolism accompanied by anomalous inferior vena
      cava with azygous continuation].
AB  - A 38-year-old man with atopic dermatitis presented with right chest pain and
      dyspnea. Previously, he had received 2mg of betamethasone daily, to prevent
      rejection of the right transplanted cornea, for 24 days. His body temperature was
      37.4 degrees C, peripheral leucocyte count measured 12,000/mm3, and C-reactive
      protein was 6.3 mg/dl. A computed tomogram of the chest revealed infiltration in
      the right lower lung field, and he was then treated for pneumonia. The second day
      he fell down one flight of stairs due to a syncopal attack and received a head
      injury. At this point his vital blood pressure was 102/55 mmHg, heart rate was
      130/min and SpO2 under breathing room air was 76%. These findings indicated
      possible acute pulmonary thromboembolism. Enhanced computed tomography revealed
      pulmonary arteries occluded by massive thrombosis and anomalous inferior vena
      cava with azygous continuation. To decrease the risk of further cerebral
      bleeding, anti-coagulation therapy was administered with only 24,000 IU/day of
      heparin. Following treatment, the patient completely recovered. We reported this
      rare case of acute pulmonary thromboembolism accompanied by anomalous inferior
      vena cava with azygous continuation.

PMID- 17233395
TI  - [A case of pulmonary Mycobacterium avium complex disease, mimicking hot tub
      lung].
AB  - A 56-year-old man in whom reticulonodular shadows had been noted on a previous
      chest radiography study was admitted to our hospital with complaint of exertional
      dyspnea in March 2004. His thoracic computed tomography (CT) showed diffuse
      ground-glass opacities and multiple centrilobular small nodules in both lung
      fields. Lymphocytes occupied a high proportion in the cells recovered from the
      bronchoalveolar lavage fluid. These findings were compatible with those for
      hypersensitivity pneumonitis. Histopathological findings observed in the video
      assisted thoracoscopic surgical biopsy specimens included necrotizing granulomas,
      organizing pneumonia associated with collective epithelioid cell granulomas
      without necrosis, and alveolar septal thickening with lymphocyte infiltration
      that showed a centrilobular distribution. These findings were also compatible
      with those for hot tub lung. Further information that supported the diagnosis
      were the identifications of Mycobacterium avium complex in his sputum by acid
      fast bacteriological culture as well as positive for Mycobacterium avium
      polymerase chain reaction in lung specimen. He responded well to corticosteroid
      therapy, resulting in improvement in his clinical condition as well as in his
      chest radiographs. He was later put on an antituberculosis therapy, and the
      corticosteroid therapy was discontinued. This led to an exacerbation of his
      disease and corticosteroid therapy was restarted. It is not long time since the
      disease was first recognized, and thus few cases have been reported in Japan. Our
      report may provide valuable information on the disease in this country.

PMID- 17233396
TI  - [Successful treatment of intrapericardial administration of carboplatin following
      systemic chemotherapy in a case of advanced thymic cancer with cardiac
      tamponade].
AB  - A 72-year-old woman developed cardiac tamponade due to direct invasion of thymic
      cancer. Carboplatin was administered into the pericardial cavity two times with a
      total dose of 600 mg. Pericardial effusion disappeared without any toxicities.
      Following four cycles of systemic chemotherapy by carboplatin, doxorubicin,
      vincristine, cyclophosphamide (ADOC), partial response was obtained. She is alive
      10 month after being given a diagnosis of cardiac tamponade. Intrapericardial
      administration of carboplatin is a useful therapy for control of pericardial
      effusion and chemosensitive cases should de identified among patients with thymic
      cancer.

PMID- 17233397
TI  - [A case of idiopathic ARDS treated by sivelestat sodium and fluid management
      based on extravascular lung water index].
AB  - A 65-year-old woman was given emergency admission with fever, cough and dyspnea.
      Chest computed tomography (CT) findings showed bilateral ground-glass opacity,
      consolidation, and this case were fulfilled the criteria for acute respiratory
      distress syndrome (ARDS). We clinically diagnosed the patient as suffering from
      idiopathic ARDS including acute interstitial pneumonia (AIP) based on the absence
      of any known causes of ARDS and systemic immunologic diseases. We started
      treatment with sivelestat sodium and strictly managed fluid balance under
      mechanical ventilation. We found this treatment quite effective because there
      were significant improvements in the extravascular lung water index (EVLWI)
      measured by the PiCCO system and neutrophile elastase value and in oxygenation
      and the chest radiograph. This is apparently the first case report in the
      literature that clearly shows the treatment with sivelestat sodium and strict
      fluid management ended in a favorable outcome, as reducing EVLWI measured by the
      PiCCO system in an idiopathic ARDS patient.

PMID- 17233398
TI  - [A case of eosinophilic bronchiolitis complicated with eosinophilic sinusitis].
AB  - A 42-year-old man was admitted to our hospital, complaining of dyspnea and cough
      for six months. Chest CT demonstrated thickening of the bronchial walls and some
      centrilobular nodules. From the laboratory data and the clinical course, he was
      first suspected to have bronchial asthma. However, it was necessary to rule out
      bronchiolitis due to other causes, because he had no previous asthma history and
      also because of the CT findings. We performed surgical lung biopsy to make a
      definite diagnosis. The pathological findings revealed eosinophilic
      bronchiolitis. While dyspnea and the eosinophilic nasal polyp improved by
      treatment with oral steroid therapy, the eosionophilic sinusitis and
      bronchiolitis relapsed after steroid tapering. Improvement and relapse of nasal
      and lower airway symptoms were synchronously observed. Eosinophilic bronchiolitis
      and eosionophilic sinusitis in this case may be considered to be a category of
      airway eosinophilic inflammation.

PMID- 17233399
TI  - [A case of hypersensitivity pneumonitis caused by zinc fume].
AB  - A 55-year-old man with a 3-year occupational history of welding was admitted for
      repeated episodes of fever, cough and dyspnea after inhalation of smoke while
      welding galvanized steel. A computed tomography (CT) showed diffuse centrilobular
      nodules, panlobular ground-glass opacity and interlobular septal thickening in
      both lung fields, and he suffered from hypoxemia (PaO2 = 55.3Torr) while
      breathing room air. Percentage of lymphocytes in bronchoalveolar lavage fluid
      increased, and lung biopsy specimens at thoracoscopy revealed lymphocytic
      alveolitis and organization in air spaces. His symptoms and signs disappeared
      spontaneously only when he ceased welding. Panlobular ground-glass opacity and
      interlobular septal thickening improved immediately with oral corticosteroids.
      Patch tests using metal series gave positive reactions to zinc. We diagnosed this
      case as hypersensitivity pneumonitis caused by zinc fumes.

PMID- 17233400
TI  - [A case of adult idiopathic chylothorax with transudative ascites].
AB  - A 70-year-old woman presented at a local clinic because of shortness of breath.
      Since she was found to have pleural effusion, she was referred to our hospital
      for further evaluation. She had no history of trauma or surgery. Pleural effusion
      examination revealed a milky-white, chylous, odorless fluid with increased
      triglycerides. Further evaluation led to a diagnosis of idiopathic chylothorax.
      Althought she was found to have transudative ascites, abdominal ultrasonography
      and computed tomography revealed no significant findings including cirrhosis of
      the liver. As a result of intravenous hyperalimentation with fasting, the chylous
      pleural fluid became serous and decreased. Ascites disappeared simultaneously,
      suggesting a possible relationship between the chylothorax and transudative
      ascites.

PMID- 17233401
TI  - [A case of HLA-B54 positive silicosis with rheumatoid arthritis and lung cancer].
AB  - In the same environment or workplace, some people contract pneumoconiosis,
      including silicosis, and some do not. This suggests the important role of
      constitutional predisposition. In Japanese cases with silicosis, the frequency of
      HLA-B54 was increased and disease susceptibility gene (s) may exist near the HLA
      B locus. It is well known that silicosis is frequently accompanied with
      rheumatoid arthritis, probably due to the effects of silica on the immunological
      system. We encountered a case of silicosis with rheumatoid arthritis and lung
      cancer, who was found to have HLA-B54.

PMID- 17233402
TI  - [Placement of an expandable metallic stent (Ultraflex) for tracheobronchial
      stenosis in relapsing polychondritis].
AB  - A 57-year-old man was admitted to our hospital because of fever, cough and
      polyarthralgia. A physical examination revealed polyarthritis and saddle nose.
      Chest computed tomography showed stenosis of the trachea and both main bronchi.
      Relapsing polychondritis (RP) was diagnosed, and steroid therapy was started.
      Dyspnea at rest appeared suddenly. Bronchoscopy showed stenosis from the trachea
      to both main bronchi. An expandable metallic stent (Ultraflex) was placed in the
      trachea and both main bronchi. After the procedure, bronchoscopy showed a widely
      patent airway, and his symptoms were improved. Since airway complications of RP
      can be fatal, tracheobronchial stent placement should be considered in the
      management of RP with airway stenosis.

PMID- 17233403
TI  - [A case of idiopathic chylothorax detected by the mass examination of chest X
      ray].
AB  - A 52-year-old asymptomatic man was referred to our hospital due to right pleural
      effusion detected on a chest X-ray mass screening. Chest X-ray film and chest CT
      showed moderate pleural effusion. The effusion was milky yellow, suggesting a
      high triglyceride level. There was no organic disease that would cause
      chylothorax so his condition was diagnosed as idiopathic chylothorax. The
      patient's right pleural effusion increased although he had been receiving
      outpatient dietary therapy for one month. He was consequently admitted to our
      hospital and received drainage of the pleural space and pleurodesis by
      intrapleural injection of OK-432. His condition was greatly improved by the
      therapy and he was discharged. There are few reports of idiopathic chylothorax in
      adults. Such a case of idiopathic chylothorax detected by chest X-ray mass
      screening has never been reported before. We, therefore, conclude that this case
      is very rare and has unique aspects.

PMID- 17233404
TI  - [A case of bullous pemphigoid associated with Pneumocystis pneumonia and
      Cytomegalovirus pneumonia].
AB  - A 68-year-old man was admitted to our hospital presenting cutaneous pruritic
      lesions consisting of tense blisters with serous content on his arms and legs.
      Histological findings of skin biopsy confirmed a diagnosis of bullous pemphigoid
      in March 2005. After 10 weeks of prednisone therapy for bullous pemphigoid, he
      presented with increasing breathlessness and high fever. He was admitted to our
      hospital because of severe hypoxemia on May 29, 2005, and mechanical ventilation
      was started from the first hospital day. Chest computed tomography showed marked
      ground-glass opacities in both lungs. The levels of beta-D glucan and KL-6 in his
      sera were elevated. We suspected Pneumocystis pneumonia and Cytomegalovirus
      pneumonia. Under mechanical ventilation, he received steroid pulse therapy, and
      sulfamethoxazole-trimethoprim and ganciclovir. A polymerase chain reaction assay
      of bronchoalveolar lavage fluid showed Pneumocysitis DNA and Cytomegalovirus DNA.
      On the 12th hospital day, he was weaned from mechanical ventilation. Follow-up
      chest computed tomography showed marked resolution of diffuse ground-glass
      opacity in both lungs. We need to consider the development of Pneumocystis
      pneumonia and Cytomegalovirus pneumonia during steroid therapy for bullous
      pemphigoid.

PMID- 17233405
TI  - [A human T-cell lymphotropic virus type 1 carrier presenting with Sjogren's
      syndrome and bronchopneumopathy].
AB  - A 77-year-old asymptomatic woman was found to have a coin lesion on a chest
      radiograph. Chest computed tomography scans showed the coin lesion,
      bronchiectasis, tree-in-bud appearance, and ground glass opacity. The
      histopathology of the lung by video-assisted thoracic surgery showed organizing
      pneumonia, follicular bronchiolitis, and non-specific interstitial pneumonitis
      patterns, all of which consisted of mainly mature lymphocytes and plasma cells.
      She suffered from dry eyes and had a high level of serum anti-SS-A antibody.
      Examination of her eyes and mouth revealed Sjogren's syndrome. The patient
      herself and her parents were born in Nagasaki prefecture, an area where human T
      cell lymphotropic virus type 1 (HTLV-1) is endemic, and her sister suffered from
      a hematological malignancy. She was found to be an HTLV-1 carrier. We finally
      made a diagnosis of an HTLV-1 carrier presenting with Sjogren's syndrome and
      bronchopneumopathy. This combination (HTLV-1, Sjogren's syndrome, and
      bronchopneumopathy) is rarely reported.

PMID- 17233406
TI  - [A proposal to "welfare method for physically handicapped person"].

PMID- 17233407
TI  - [Cancer pain model and morphine analgesia].

PMID- 17233408
TI  - [The palliative care in the clinical oncology].
AB  - With the development of the medical oncology, the progress of the diagnosis and
      the treatment for cancer patients have provided the improvement of overall
      survival rates. Furthermore, the importance of the palliative care, which give
      the relief of the pain and maintain or improve quality of life in cancer
      patients, has become to be recognized recently. Because the palliative care aims
      to provide the cancer patients and families with the relief of "total pain",
      which means the complex etiology of pain, including its physical, emotional,
      social, economic, and spiritual components, it has been adapted not only at the
      terminally period but also at the beginning of the cancer treatment. Therefore,
      an interdisciplinary collaboration with a variety of experts is required for
      palliative care. Although there is a lot of problem to be solved for palliative
      care in Japan, each expert should investigate his own speciality but also
      collaborate with another.

PMID- 17233409
TI  - [Current perspectives and future direction of palliative medicine for cancer
      patients in Japan].
AB  - Role of palliative medicine for cancer patients has been expanding to even in
      earlier stage of disease. We have various new drugs in palliation of symptoms and
      signs, such as severe pain due to tumor invasion, depression, nausea and
      vomiting, chemotherapy-induced anemia and neutropenia, etc. Recently
      pharmacogenomics and drug metabolism became to be focused in cancer treatment. It
      may cause unexpected toxicity due to drug-drug interaction and may raise
      unreasonably lower effect due to individual heterogeneity of drug metabolism. To
      facilitate and maintain better-quality palliative medicine allover Japan, a well
      organized educational system and multi-institutional research groups should be
      established on the basis of a large academic and clinical association. The
      Japanese Society of Palliative Medicine (JSPM) is one of the candidate of these
      tasks. The JSPM consists with more than 4,900 members of doctors, nurses and
      other health professionals who are working in palliative cancer medicine. They
      have conducting to make guidelines for each symptom control and to increase lobby
      action to establish efficient networks of palliative cancer medicine in each
      district of Japan within several years.

PMID- 17233410
TI  - [Characteristics of and strategy for cancer pain].
AB  - 75% of cancer patients have pain, which can greatly affect their quality of life.
      In cancer patients, not only physical pain but also total pain must be treated.
      Cancer pain can be classified as nociceptive pain or neuropathic pain according
      to neural mechanism. It is important to consider the underlying cause and
      mechanism. In 80% to 90% of patients, pain can be alleviated by the WHO (World
      Health Organization) guidelines, which have been established as standard
      treatment for cancer pain. Therefore, all physicians involved in cancer care
      should become skilled in this analgesic therapy. This article mainly explains the
      characteristics of cancer pain and the WHO guidelines.

PMID- 17233411
TI  - [Assessment of pain].
AB  - Assessment of patient's pain is crucial to effective pain management. It requires
      not only the knowledge of pain scale, but also a closely listening ear and a
      sharp eye. It also needs to be constantly re-evaluated by the healthcare team.
      While taking pain history, encourage the patient to do most of the talking and
      explain the pain characteristics with his/her own words. This is important when
      classifying the pain to predominantly nociceptive or neuropathic pain. Since
      cancer pain is not purely acute pain, assessment of pain needs not only to
      evaluate pain scores but also to evaluate patients' physical function and the
      impact of pain on his/her daily activities. Assessing secondary effect of pain,
      such as anxiety or financial worries, and reducing them may decrease the overall
      experience of pain.

PMID- 17233412
TI  - [The feature and direction of each controlled release morphine].
AB  - Recent advances in cancer pain management resulted with rapid spread of variety
      of opioids in Japan. During these two decades, many controlled release morphines
      for cancer pain management have been released in the Japanese market. As severe
      pain is most common and dreadful symptom in cancer patients, all physicians
      should learn correct information about opioid analgesics. In this article, the
      feature and direction of each controlled release morphine are described.
      Moreover, the target and method of cancer pain treatment are also described.

PMID- 17233413
TI  - [Best practice of pain management with opioids].
AB  - Opioids are main drugs in pain management for terminal cancer patients. In these
      days, we have to choice suitable opioids for the terminal cancer patients with
      severe pain by opioids rotation. Morphine is a basic drug in opioids. To know
      about character of morphine make us easy for using other opioids. In this
      article, character and some points in using opioids were described in detail. For
      example, timing for administrating opioids, titration, rescue dose, and side
      effects were included in this article. We don't have to remember the aim of pain
      management. Pain control is not a purpose, but a way for keeping QOL of the
      terminal cancer patients.

PMID- 17233414
TI  - [Patient education in cancer pain management with opioids].
AB  - It is important for pharmacists to remove patients' anxiety and misunderstanding
      about cancer pain management with opioids. Furthermore, we need to explain how to
      take opioids as well as its effects and side-effects and make sure they are
      correctly understood so that patients and their family members adequately use the
      medicine. Here describes the patient education which aims to remove patients'
      anxiety and misunderstanding about opioids and urge patients to be proactively
      involved in cancer pain management.

PMID- 17233415
TI  - [Non-opioid analgesics in cancer pain].
AB  - Non-opioid analgesics (NSAIDs, acetaminophen) are the most basic drugs used from
      the first to third steps according to the WHO analgesic ladder. Even after the
      initiation of the use of opioids, improvement in pain is observed by the
      continuation of non-opioid analgesics. NSAIDs have anti-inflammatory effects and
      are particularly effective against somatic pain represented by that due to bone
      metastasis. On the other hand, NSAIDs should be prescribed with adequate
      attention being paid to side effects (gastrointestinal disorders and nephropathy)
      due to long-term administration. Acetaminophen with few side effects is useful
      for long-term administration, and its use is recommended.

PMID- 17233416
TI  - [Present status of the use of adjuvant analgesics in Japan].
AB  - Adjuvant analgesics are drugs that have primary indications other than pain but
      are analgesic in selected circumstances. Antidepressants, anticonvulsants, local
      anesthetics, and NMDA receptor antagonists are drugs used in the treatment of
      neuropathic cancer pain. Assessment of pain is very important in selecting
      appropriate adjuvant analgesics. The assessment includes visual analog scale for
      pain intensity, McGill Pain Questionaire for quality of pain, and the location of
      pain. It is also important to assess the effectiveness of immediate release
      opioids. Most neuropathic pain is thought to be refractory to opioids. In Japan,
      effective adjuvant analgesics such as gabapentin and pregabalin are not
      available. The main adjuvant analgesics are still tricyclic antidepressants such
      as amytriptylin and amoxapin, and anticonvulsants such as carbamazepin and
      clonazepam. Another problem is that morphine is the only rescue drug available
      for the assessment of opioid responsiveness since morphine is the only opioid
      with an immediately release form among the strong opioids available in Japan
      which are morphine, oxycodone, and fentanyl. Adjuvant analgesics also have side
      effects such as constipation and sleepiness, which may augment the side effects
      of morphine and may impair the QOL of cancer patients with neuropathic pain.
      There is a need to improve the systems of development and importation of adjuvant
      analgesics.

PMID- 17233417
TI  - [Dyspnea in cancer patients].
AB  - 'Dyspnea' is a subjective symptom defined as "an uncomfortable sensation of
      breathing". It should be distinguished from 'respiratory failure' defined as
      hypoxia. It is important to know that dyspnea is also related to psychological
      distress such as anxiety. The important points of management of dyspnea are
      described here; (1)Treat the underlying causes (e.g. antibiotics for pneumonia,
      blood transfusion for anemia), (2) pharmacological interventions such as morphine
      and anxiolytics, (3) non-pharmacological interventions such as oxygen,
      respiratory rehabilitation and relaxation. Since dyspnea in cancer patients has
      multidimensional aspects, interdisciplinary team approach for the symptom
      management is important.

PMID- 17233418
TI  - [Appetite loss, nausea, vomiting].
AB  - Appetite loss, nausea and vomiting are most common gastrointestinal distress in
      patients with advanced cancers. It is worthwhile to relieve these symptoms for
      improving their quality of life (QOL), an inadequate treatment, on the contrary,
      will increase their distressing symptoms. To avoid this, it is essential to
      clarify the cause of illness, especially to find out whether it is due to a
      complete mechanical gastrointestinal obstruction or not. If it is so, the use of
      metoclopramide is a contraindication. Practically, the combined use of octreotide
      acetate, steroids and morphine will be effective to manage a severe
      gastrointestinal distress such as an obstinately nausea and vomiting.

PMID- 17233419
TI  - [Symptom with bone metastasis--bone pain, fracture, hypercalcemia].
AB  - Bone metastasis is in 60-84% of a metastatic cancer case. Bone metastasis itself
      does not cause a pain by all means, but even if bone metastasis contributes to
      40% of cancer pain, it is said, and it is an important subject of a cancer pain
      treatment. Because it is a lot progressive as well as an unbearable pain, bone
      metastasis becomes cause by the fact that the pain is remarkable and inhibits QOL
      of the patient. On this account that a treatment of bone metastatic pain merely
      takes a pain by pharmacotherapy. Preventing pathologic fracture and a
      complication such as spinal cord compression and a treatment of hypercalcemia are
      important. In addition, we do surgical treatment and radiation therapy for the
      fracture that occurred positively and must deal generally.

PMID- 17233420
TI  - [Lymphedema].
AB  - It is necessary to do treatment that centered on the compression therapy after
      examining the condition closely enough to treat the lymphedema (so-called
      malignant lymphedema) that developed by the progress of cancer. As the
      compression method, the method of using the elastic bandage is general, and,
      according to circumstances, the elastic stocking is used. Moreover, not only the
      patient but also the family feels and self care what is important. It is thought
      that the manual lymph drainage to affected limbs is also effective to think about
      the symptom reduction of affected limbs as palliative medicine because of the
      purpose is not to improve the edema.

PMID- 17233421
TI  - [Surgical intervention in palliative care].
AB  - In palliative care, surgical intervention is contra-indicated if there is intra
      abdominal carcinomatosis as evidenced by diffuse intra-abdominal tumors, and
      massive ascites which re -accumulates rapidly after paracentesis. Surgical
      intervention should be considered, if the following criteria are fulfilled even
      in palliative care. (1) The patient' s general condition is good, i.e. does not
      have widely disseminated disease and has been independent and active. (2)
      Previous laparotomy findings do not preclude the prospect of successful
      intervention. (3) An easily reversible cause seems likely, e.g. postoperative
      adhesions or a single discrete neoplastic obstruction. (4) The patient is willing
      to undergo surgery. In patients in whom an operative approach is contra
      indicated, it is generally possible to relieve symptoms adequately with drugs, a
      nasogastric tube and i.v. fluids are rarely necessary.

PMID- 17233422
TI  - [Radiation therapy in palliative care of cancer patients].
AB  - Since westernization of cancer profile and our aging society, the number of
      radiation therapy is increasing in this country. When compared to surgical
      operation and chemotherapy, the patient's adverse effects by radiation therapy
      are relatively limited. This is the reason why this treatment modality is used
      most frequently as a palliation of terminal-stage cancer patients. Radiation
      therapy gives not only pain relief of the tumor lesion, but also local control of
      the disease to prevent pathological fracture, spinal cord compression, or brain
      metastasis. Recently, technical innovations in this field actualizes pinpoint
      dose concentration to the cancer lesion, which benefits advanced or terminal
      cancer patients as well. Clinical usefulness of radiotherapy in the palliative
      medicine is documented.

PMID- 17233423
TI  - [Palliative chemotherapy in cancer patients].
AB  - Palliative chemotherapy is applied for incurable cancer patients to prolong their
      survival, decrease their cancer-related symptoms, and improve their quality of
      life. These are important end points in clinical trials of palliative
      chemotherapy. A lot of clinical studies have demonstrated the palliative effect
      of chemotherapy for incurable cancers such as advanced pancreatic cancer, non
      small cell lung cancer and so on. On the other hand, treatment with anti-cancer
      drugs can be harmful, and sometimes the toxicities may be very severe leading to
      worsened quality of life and shortened survival. So, we must carefully consider
      the application of palliative chemotherapy and discuss it with patients.

PMID- 17233424
TI  - [Cancer pain treatment with nerve blocks and neuroablative procedures].
AB  - The management of opioid resistant cancer pain is a significant issue for
      palliative medicine. Certain types of pain can be relieved effectively using
      nerve blocks without exacerbating and sometimes improving daily activity as long
      as proper patient selection and technique are employed. Continuous epidural and
      subarachnoid block, celiac plexus block, superior hypogastric plexus block,
      subarachnoid phenol block and percutaneous cervical cordotomy are common pain
      treatment procedures. In our pain clinic, these procedures were performed on
      about 20% of cancer pain patients, most of whom experienced pain relief without
      serious complications. Proper use of nerve blocks and neuroablative procedures
      can undoubtedly improve the management of cancer pain and should be a significant
      component of the strategy for cancer pain relief.

PMID- 17233425
TI  - [Current perspectives of psycho-oncology in Japan].
AB  - The Japanese Psycho-Oncology Society (JPOS) was founded in 1987, while the
      Japanese Society of General Hospital Psychiatry (JSGHP) in 1988. Inspired by the
      International Congress of Psycho -Oncology Society (IPOS) meeting which was held
      in 1995 in Kobe, many general hospital psychiatrists joined to the activity of
      the JPOS. In these ten years, many studies were conducted on the following
      topics: truth-telling, psychiatric co-morbidity, psychosocial intervention, etc.
      And recently, the activity of palliative care team including a psychiatrist has
      been reimbursed, which will be hopefully a new step to the progress of psycho
      oncology in Japan. Also, a collaboration between the JPOS and the JSGHP will be
      strongly needed to make a remarkable progress.

PMID- 17233426
TI  - [Pharmacological therapy for psychiatric issues among cancer patients].
AB  - It is reported that the common psychiatric disorders among cancer patients are
      adjustment disorder, major depression, and delirium. Pharmacotherapy is often
      provided for management of these distressing symptoms. Antianxiety drugs,
      especially benzodiazepines, are often used for ameliorating adjustment disorder.
      Among them, shorter-acting benzodiazepines are usually preferred. Several
      randomized clinical trials indicate the efficacy of antidepressants for
      management of major depression experienced by cancer patients. Because there are
      no significant differences of effectiveness among available antidepressants, it
      is recommended that selection of antidepressant should depend on its adverse
      event profiles. Although the principal management strategies of delirium are
      detection and treatment of underlying causes of delirium, concurrent
      pharmacotherapy as symptomatic treatment is often needed. Neuroleptics,
      especially haloperidol, are most widely used for management of delirium.

PMID- 17233427
TI  - [Practice of psychotherapy for cancer patients].
AB  - Cancer is a threat to life and to the psychological well-being of patients.
      Previous studies have demonstrated that several patients with cancer have
      suffered from psychological distress. Psychotherapy for cancer patients is
      effective against psychological distress. There are several kinds of
      psychotherapy for these patients, such as supportive psychotherapy, cognitive
      behavioral psychotherapy including relaxation techniques and cognitive
      restructuring, and supportive-expressive group psychotherapy. Supportive
      psychotherapy is feasible for many clinicians. Psychotherapists develop a
      trustful relationship with patients, provide an empathic posture, and use various
      types of psychotherapeutic treatments. It is important for psychotherapists to
      understand the psychological background of such patients from various viewpoints.

PMID- 17233428
TI  - [Palliative care in Seirei Mikatahara General Hospital Department of Palliative
      and Supportive Care, Seirei Mikatahara General Hospital].
AB  - This paper illustrates a brief review of the development process of the
      palliative care team at the Seirei Mikatahara General Hospital. Palliative care
      team has been first instituted in 2002, and currently providing general support
      for cancer patients receiving chemotherapy not only for terminally ill patients.
      In future, we would start a regional palliative care program, including community
      palliative care team, to provide appropriate palliative care for all cancer
      population.

PMID- 17233429
TI  - [The role of psychiatrist in the team].
AB  - The palliative care team has started to organize in Japanese Hospital since 2002,
      because Japanese government established financial support to this kind of team.
      It was required that psychiatrist participated in the team, therefore, it has
      been discussed the role of psychiatrist. According to current palliative care in
      Japanese hospital, the author mentioned the role of psychiatrist in the team. As
      the role of a psychiatrist, there are psychiatric assessments and treatments for
      cancer patients, psychological supports for families, and supports for medical
      staffs. The problems of psychiatrist in the palliative care team are; hard to
      take enough time for those treatments and supports, an insufficient education
      system to young psychiatrist, and poor evidence to establish the standard
      psychiatric treatment.

PMID- 17233430
TI  - [Evaluation of cancer pain--possibility of biomarkers].
AB  - The accurate assessment of pain is needed to control cancer pain and its
      treatment. Pain itself is subjective experience and is difficult to estimate
      quantitatively. Until now, there is no precise method to quantitate the cancer
      pain objectively. First, we show the tools to assess cancer pain by patient's
      description, including visual analogue scales, verval rating scales and numerical
      rating scales and so on. These scales have been used to evaluate the intensity of
      clinical pain, however they cannot assess the quality of cancer pain and only
      McGill Pain Questionnaire (MPQ) has specificity for the qualitative and
      quantitative properties of clinical pain. Molecular biological approach has been
      advanced in the neuroscience field to find the candidate of neuropathic pain. In
      this article, we would like to show the results of the proteomics research for
      neuropathic pain. We also tried to discuss about the biomarker and its
      possibility whether it can reflect cancer pain and effect of cancer treatment.

PMID- 17233431
TI  - [Efficacy of bisphosphonates for bone pain control].
AB  - Bone metastasis of malignant tumors causes various skeletal related event(SRE)
      and often harms patients' quality of life (QOL). Bisphosphonate is a standard
      treatment medicine for the patient with bone metastasis of malignant tumors.
      Especially zoledronic acid is recommended for bone metastasis of all malignant
      tumors in a guideline of American Society of Clinical Oncology (ASCO). Zoledronic
      acid also consistently reduced brief pain inventory (BPI) composite pain scores
      from baseline and compared with placebo in Japanese women with bone metastases
      from breast cancer. Bisphosphonates bring about benefit for the patient who
      suffers from bone pain.

PMID- 17233432
TI  - [Quality of life assessment in cancer palliative care].
AB  - In the palliative cancer care field, few qualified evidences about health
      outcomes, e.g., quality of life (QOL), have been produced and applied to daily
      care. This article firstly describes the reality of qualified evidences in this
      field examined by MEDLINE search, and introduces some of the recently published
      qualified papers. Secondly, this article introduces some of the standard methods
      how to select appropriate QOL instruments. Finally, this article reviews recent
      topics about concepts and theories for health outcomes assessments.

PMID- 17233433
TI  - [Molecular mechanisms in the development and progression of pancreas and biliary
      tract cancers].
AB  - Pancreatic and biliary tract cancers are the most lethal malignancies in the
      gastrointestinal tract. Investigators have actively investigated to elucidate
      molecular mechanisms involved in the carcinogenesis, growth, invasion and
      metastasis of these cancers. This review describes those molecular mechanisms and
      their correlation with clinicopathological features of pancreatic and biliary
      tract cancers. Furthermore, recent experimental developments in the gene therapy
      technologies toward these cancers are also summarized.

PMID- 17233434
TI  - [Infection control strategies for antimicrobial-resistance].
AB  - Antimicrobial-resistance (AMR) is a growing threat especially to critically ill
      patients, because treatment failure can have serious consequences. MRSA has been
      a major concern in Japanese hospitals, however, emerging the drug-resistant
      pathogens that comprise VRE, MDRP or ESBL have been reported as nosocomial
      infectious pathogens. To control antimicrobial-resistance, antimicrobial therapy
      according to local sensitivity result and multidisciplinary management is
      necessary. CDC recommends 12 steps to prevent AMR among hospitalized patients,
      which included prevent infection, diagnose and treat infection effectively, use
      antimicrobials wisely, and prevent transmission. Infectious diseases experts, who
      are far lacking in Japan, may play a key role to achieve these recommendations.

PMID- 17233435
TI  - [Application and limitation of nasal-paranasal office surgery].

PMID- 17233436
TI  - [Prediction of the date of Japanese cedar pollen release in Aomori Prefecture].
AB  - When we treat patients with pollen allergy, we require correct information about
      pollen release. The total count of pollen and the date of first pollen release
      are strongly influenced by local weather conditions, so we wanted to predict
      local pollen release. Patients have degrees of sensitivity to pollen, with
      symptoms triggered in some cases by only small amounts. Therefore, we wanted to
      determine the previous dates of first pollen release (A), the first of two
      consecutive dates when one (count/cm2) or more grains were released (B), and the
      first of two consecutive dates when ten (count/cm2) or more grains were released
      (C). Aomori Prefecture has three different weather zones because it is surrounded
      by three oceans the Sea of Japan, the Pacific Ocean, and Mutsu Bay. We predicted
      pollen release in the major cities--Aomori, Hirosaki, and Hachinohe. Using nine
      years (1996-2004) of temperature data for each city from January 1 through
      February 1, we recorded the number of days in which the daily highest temperature
      was higher than each of five set temperatures (0 degree C, 1 degree C, 2 degrees
      C, 3 degrees C, 4 degrees C) up to the dates of A, B, and C. Multiple recordings
      were made for each year with the initial date of recording staggered at 10-day
      intervals. We then calculated the standard deviation and the efficient of
      variation of total days and totals of temperatures over set temperatures. For
      Aomori, results indicated that A was predicted as day 19 with temperatures over 4
      degrees C after January 21. B was day 23 over 4 degrees C after January 21. C was
      the day 31 with over 4 degrees C after January 21. For Hirosaki, A was expected
      to be day 26 having temperatures over 0 degrees C after February 1. B was day 21
      over 3 degrees C after February 1. C was day 30 over 3 degrees C after January
      21. For Hachinohe, A was day 34 with temperatures over 0 degrees C after February
      1. B was day 33 over 1 degree C after January 21. C was day 27 over 4 degrees C
      after January 21. We examined the day of pollen release in 2005.

PMID- 17233437
TI  - [Survey of nasopharyngeal carriage of Haemophilus influenzae and Streptococcus
      pneumoniae in infants at day care centers].
AB  - Infants at day care centers tend to contract repetitive upper respiratory
      infections and prolonged otitis media. The increase in antimicrobial-resistant
      bacteria, particularly in infants, has given rise to a stubborn therapeutic
      problem. We studied the nasopharyngeal carriage and drug resistance to
      Haemophilus influenzae (H. influenzae) and Streptococcus pneumoniae (S.
      pneumoniae), the most common pathogens of upper respiratory infections, in
      infants at day care centers. Nasopharyngeal cultures of infants between the ages
      of 0 and 6 years were conducted at two day care centers in July 2004 ("summer";
      n=183), and in February 2005 ("winter"; n=182). Isolated H. influenzae and S.
      pneumoniae were subjected to antibiotic susceptibility tests by broth
      microdilution. We also conducted an otolaryngological examination and a survey on
      past and life histories. H. influenzae in summer (38.3%) increased significantly
      in winter (57.7%). Beta-lactamase-negative and positive ampicillin-resistant H.
      influenzae (BLNAR+ BLPAR) in summer decreased significantly in winter. S.
      pneumoniae did not differ in summer (42.1%) or in winter (43.4%). Penicillin
      resistant and intermediate S. pneumoniae (PRSP+PISP) was 41.3% in summer and
      decreased significantly to 19.0% in winter. BLNAR + BLPAR and PRSP + PISP
      differed with the day care center. In otolaryngological examination,
      rhinosinusitis was commonest (28.4% in summer and 30.8% in winter), followed by
      allergic rhinitis (8.7% in summer and 6.0% in winter) and otitis media (8.2% in
      summer and 6.0% in winter). Tonsillitis was minor (0.5% in both seasons).
      Rhinosinusitis in winter was significantly higher in carriers of H. influenzae
      and/or S. pneumoniae than in non carriers (36.4% versus 16.0%). Breast-fed
      infants tended to have less otitis media than bottle-fed infants (38.2% versus
      52.9%). H. influenzae and/or S. pneumoniae plateaued (75-80%) after 12 months in
      day care centers. These results suggest that infants attending day care centers
      are immediately colonized by H. influenzae and S. pneumoniae in the nasopharynx
      after entering the centers. Nasopharyngeal drug-resistant H. influenzae and S.
      pneumoniae varied during the seasons and between day care centers. Further
      prospective studies are needed to determine upper respiratory tract infection in
      infants at day care centers and to evaluate carriage, epidemiology, and the drug
      resistance rates of these pathogens.

PMID- 17233438
TI  - [Effects and use of the suture direction mimicking only the force action of the
      lateral cricoarytenoid muscle in arytenoid adduction combined with thyroplasty
      type I].
AB  - Isshiki's arytenoid adduction combined with thyroplasty type I is a useful
      procedure for correcting the membranous vocal fold atrophy and the height
      difference between the two vocal folds, particularly in patients with a large
      posterior glottal chink and atrophy. Conventional arytenoid adduction (Isshiki's
      arytenoid adduction) is designed to place a suture through the muscular process
      of the arytenoid attached anteriorly to the thyroid ala, stimulating the function
      of the thyroarytenoid muscle and lateral cricoarytenoid muscle. Combining with
      thyroplasty type I, the suture direction of conventional arytenoid adduction
      prevented inserting implant material into the pocket of the thyroid cartilage
      window. In contrast to conventional arytenoid adduction, the suture direction in
      our approach is anchored anteroinferiorly, mimicking only the action of the
      lateral cricoarytenoid muscle (the major adductor of the larynx). It is used the
      thyroid cartilage window in thyroplasty type I to determine the direction of the
      lateral cricoarytenoid muscle. After approaching the muscular process based on
      Isshiki's arytenoid adduction, two nylon sutures are tied across the muscular
      process or the lateral cricoarytenoid muscle nearby the muscular process. The
      cricoarytenoid joint is not dislocated. One of the sutures was anchored to the
      inferior rear corner of the thyroid cartilage window to be used with thyroplasty
      type I and the other was anchored to the rear lower margin of the thyroid lamina.
      Gore-tex medialization thyroplasty is done after tying the sutures on the thyroid
      ala. Subjects were 30 unilateral paralytic dysphonia. Maximum phonation of all
      patients improved significantly after surgery. The preoperative and postoperative
      mean maximum phonation times were 6.0 and 17.9 seconds. No major complications
      occurred in this study. Our approach effectively combined arytenoid adduction and
      thyroplasty type I for patients with severe insufficient glottic closure.

PMID- 17233439
TI  - [Recent progress of COPD management].

PMID- 17233440
TI  - [Recent progress in Klotho research].

PMID- 17233441
TI  - [Medical service for old ages in local community].

PMID- 17233442
TI  - [Present state and future prospect of geriatric emergency medicine].

PMID- 17233443
TI  - [An epidemiological review on morbidity of the elderly in Japan].

PMID- 17233444
TI  - [Usefulness and limitation of comprehensive geriatric assessment].

PMID- 17233445
TI  - [Reperfusion therapy for acute myocardial infarction in elderly patients].
AB  - Although there has been great progress in reperfusion therapy, the role of
      coronary reperfusion for elderly patients with acute myocardial infarction has
      not been fully investigated. In general, mean age of the subjects in major trials
      was about 60 years old and approximately only 10 to 15% of patients were over age
      75. On the other hand, large-scale registries such as the US national registry of
      myocardial infarction (NRMI) showed a higher prevalence of elderly (especially
      women) in the clinical setting. This discrepancy may be due to the fact that
      elderly patients with myocardial infarction have some difficulties in the
      treatment such as severe multi-vessel coronary lesions, non-cardiac complications
      and relatively high prevalence of adverse reactions to reperfusion therapy. Here
      we focus on the situation of elderly patients (especially those 75 years or
      older) with myocardial infarction in the "real world" clinical setting, showing
      the clinical changes and outcome of our registry in rural Japan: the Kochi AMI
      (KAMI) registry.

PMID- 17233446
TI  - [Antihypertensive therapy in very-old patients].

PMID- 17233447
TI  - [The socio-medical issues of elderly diabetic patients].

PMID- 17233448
TI  - [Characteristics and treatment of elderly coronary heart disease patients].

PMID- 17233449
TI  - [Hypertension in the elderly].

PMID- 17233450
TI  - [Metabolic syndrome in elderly].

PMID- 17233451
TI  - [Characteristics of arrhythmia in elderly patients].

PMID- 17233452
TI  - [Heart failure in the elderly].
AB  - Heart failure (HF) is a major disease of the elderly. Since their symptoms of HF
      are generally light, on admission of the hospitals HF is sometimes in an advanced
      stage. Therefore, preventive medicine for those with the risk factors of HF is
      needed as a future strategy of cardiac gerontology. The routine assessment of the
      HF severity may be performed noninvasively by Nohria's profiles rather than other
      invasive methods. HF is worsened by the interaction with the co-morbidity
      factors, such as renal dysfunction and anemia. The interaction between HF and
      kidney disease (and anemia) is called 'cardiorenal (anemia) syndrome.' Recurrent
      hospitalization due to HF is common, and the period of hospitalization tends to
      be long in this syndrome. One of the hopeful therapeutic agents is carperitide, a
      recombinant human atrial natriuretic peptide. In cardiorenal syndrome, much lower
      initial doses of carperitide, such as 0.0125 microg/kg/min is recommended for
      treatment of HF in order to avoid possible worsening of renal dysfunction. In
      cardiorenal anemia syndrome, supplement of iron, careful blood transfusion in
      severe cases, administration of recombinant human erythropoietin, should be
      performed if indicated. However, the possibility of anemia unrelated to HF, such
      as due to gastrointestinal carcinoma, is also considered in the elderly. In such
      cases, finding a decrease of serum ferritin preceding that of hemoglobin may
      contribute to a differential diagnosis of anemia in elderly HF patients. Thus,
      the therapies considering several features of HF in elderly will contribute to
      improving quality of life and outcome.

PMID- 17233453
TI  - [Current status of cardiovascular surgery for aged patients].

PMID- 17233454
TI  - [The role of a multidisciplinary approach in geriatric care and rehabilitation
      from the acute to the chronic stage].
AB  - A multidisciplinary team for bed sores consisted of 10 members including 3
      dermatologists, 3 nurses, 1 physical therapist (PT), 1 pharmacist, 1 dietician,
      and 1 medical clerk. The incidence of new bed sores after admission was
      significantly decreased from 3.31% in 2003 to 1.04% in 2005 (P < 0.01). A total
      of 324 percutaneous endoscopic gastrostomy (PEG) procedures were performed from
      2001 to January 2006. Among those, the survival of 172 elderly patient (aged 65
      years or older at the time of PEG) was calculated by the Kaplan-Meier method. The
      30-day mortality rates was 11%, and the 1-year, and 5-year survival rates were
      61.2%, and 34.4% respectively. After discharge, 40 patients were followed up at
      the PEG clinic in our hospital whose staff consisted of 1 expert surgeon, 5
      nurses and 1 dietician. When compared with 67 patients transferred to other
      hospitals or nursing homes, the patients in the PEG clinic showed a significantly
      longer survival (P < 0.01, 44 versus 29 months). A full-time integrated treatment
      (FIT) program for stroke rehabilitation was developed in the Nanakuri-Sanatorium
      of our university in 2000. Eighty-one stroke patients were on the FIT program
      during their hospital stay and achieved significantly higher activities of daily
      living (ADL) scores (P < 0.01) at discharge assessed by functional independence
      measure (FIM) compared to 41 patients on previous rehabilitation program. In
      addition, their ADL scores were maintained significantly higher (P < 0.05) even
      at 18 month after discharge, which might help them to stay home independently or
      with less care burden. These results suggest the important role of
      multidisciplinary approach for geriatric care and rehabilitation.

PMID- 17233456
TI  - [Continuous positive airway pressure (CPAP) is also the first choice therapy for
      obstructive sleep apnea patients in old age].

PMID- 17233455
TI  - [The combination of "Careworks" insurance plan integrated with medical and long
      term care insurance].
AB  - The social security system in Japan was greatly revolutionized when the long-term
      care insurance plan began in April 2000. Thus, Japan began the 21st century with
      two great social insurance plans, that is, medical care insurance and long-term
      care insurance. Each delivery system is divided: the medical care insurance plan
      is for the acute stage, and the long-term care is for the chronic stage. Both
      systems can be intended to cooperate to provide continuous care throughout life.
      The public health and welfare system has been trying hard to efficiently
      integrate the medical and long-term care insurance plans. However, it is
      necessary to establish a new insurance plan for ensuring the integrated adequacy
      of both insurance systems. One's life is destined to shift from medical care to
      long-term care at some point. As one ages or becomes disabled, it becomes
      difficult to lead an independent life with self-decision, and social support
      become necessary from third parties, instead of from the family or from one's own
      means. The society imposes the responsibility of payment of the medical and long
      term care plan premiums on the individual throughout life. However, the structure
      of these insurance foundations should be combined under an integrated system,
      "Careworks", in order to also combine the concepts of length of life from the
      medicine and the respect of living from the long-term case to improve the social
      security of the life.

PMID- 17233457
TI  - [The continuous positive airway pressure is not always the first choice of the
      therapy for sleep apnea syndrome in the elderly].

PMID- 17233458
TI  - [Strict management for the purpose of improving prognosis is recommended in
      elderly diabetic patients].

PMID- 17233459
TI  - [Treatment strategy for diabetes in elderly: less intesive treatment should be
      necessary to keep better QOL].

PMID- 17233460
TI  - [Examination of frontal lobe function of Parkinson disease patients using Stroop
      reaction time].
AB  - The purpose of this study is to examine frontal lobe function of non-dementia
      Parkinson's disease (PD) patients. We examined the neuropsychological and
      behavioral evaluation (Stroop reaction time: SRT). Target image (20%) and non
      target image (80%) were presented to PD patients, healthy elderly controls, and
      healthy young subjects at random. We instructed subjects that the button should
      pressed on the target image. This study was designed to investigate the mental
      set under three conditions. The Stroop test, Word Fluency Test (WFT), and
      Geriatric Depression Scale (GDS) were used to assess cognitive function. The SRT
      of PD were congruent condition and incongruent condition increased compared with
      simple condition. The delay of a similar SRT was seen in the healthy elderly
      control and young groups. However, the SRT of PD patients was slower under
      incongruent condition than under congruent condition. It appears that PD spent
      time on judgment in under incongruent condition because the meaning of the
      character did not correspond to the color of the character. Because, there were
      no significant between PD and healthy elderly subjects in Stroop test, WFT, and
      GDS, frontal lobe function had a partial deficit. The SRT of PD was increased by
      the partial deficit in information processing ability in addition to movement
      dysfunction.

PMID- 17233461
TI  - [Relationships of swallowing function to changes in motor functions in stroke
      patients with motor dysphagia].
AB  - AIM: To clarify the clinical features of physical therapy for motor dysphagia by
      identifying changes in indices when swallowing function changes. METHOD: Subjects
      comprised 59 stroke patients with motor dysphagia. They were subdivided into 3
      groups according to changes in swallowing function (Group A: improved, Group B:
      deteriorated. Group C: unchanged). Measured indices for swallowing movement
      consisted of 4 items; distance from the genion to the thyroid cartilage (GT),
      distance from the thyroid cartilage to the sternum (TS), relative thyroid
      position (GT/(GT + TS)), and strength of the suprahyoid muscles (GS grade).
      Measured indices for neck-trunk function consisted of the passive neck range of
      motion in 4 directions (flexion, extension, lateral flexion, and rotation), and
      neck-trunk-pelvis stage (NTP stage) as described by Yoshio. Measured indices for
      swallowing function were the repetitive saliva swallowing test, the modified
      water swallowing test, the food test, and Saitoh's classification of dysphagia.
      RESULTS: Group A consisted of 30 patients (mean age, 68.1 years), Group B
      consisted of 6 patients (mean age, 78.7 years), Group C consisted of 23 patients
      (mean age, 73.0 years). Group A exhibited significant improvements in GS grade,
      NTP stage, neck extension and rotation. In Group B, only relative thyroid
      position was affected. In Group C, no changes were evident. CONCLUSION: To obtain
      improved swallowing function, approaches aimed at both local function of
      swallowing muscles and neck-trunk function should be used. Preventing
      deterioration of swallowing function requires attention to thyroid position
      affected by inappropriate posture.

PMID- 17233462
TI  - [Development of a rating scale for self-efficacy of physical activity in frail
      elderly people].
AB  - AIM: The purpose of the present study was to 1) development the scale of the self
      efficacy of physical activity in frail elderly people (SEPAF), 2) investigate the
      relationship of physical functions and instrumental activity of daily living
      (IADL). METHODS: The study included 187 community-dwelling elderly people.
      Subject's SEPAF (walking, stair-climbing, lifting a weight), physical functions
      (usual gait speed, maximum gait speed, knee extension muscle strength, hand grip)
      and IADL according to the Tokyo Metropolitan Institute of Gerontology Index of
      Competence (TMIG Index of Competence) were measured. The reliability of this
      scale was examined using Cronbach's alpha, and test-retest correlation. The
      criterion-related validity and the construct validity were evaluated relatively
      using physical functions and factor analysis. The score was compared between
      young-old and old-old and gender. The correlation between SEPAF and TMIG Index of
      Competence was examined. RESULTS: Cronbach's a showing internal consistency for
      these scales were 0.78-0.82. The score showed significant differences in gender
      and age group. There were significant relationships between SEPAF and physical
      functions, and the TMIG Index of Competence. CONCLUSION: The SEPAF was shown to
      be highly reliable. Few scale for frail elderly people exist, and it is useful to
      assess the self-efficacy of physical activities in frail and community-dwelling
      elderly people.

PMID- 17233463
TI  - [Characteristic of elderly patients with ulcerative colitis and therapeutic
      issue].
AB  - AIM: Ulcerative colitis (UC) primarily affects young adults, but the proportion
      of elderly patients with UC seems to be increasing. It is important that the
      clinical characteristics of elderly patients be analyzed. METHODS: In the older
      group consisted of 32 outpatients (23 aged 50-64 years old, 9 aged 65 or over) in
      our hospital, we evaluated disease duration, severity, therapeutic efficacy and
      other clinical problems. RESULTS: The age distributions of the disease onset
      showed a peak at early age and decreased with aging. The degree of severity was
      mainly mild, and left-sided or pancolitis were more frequent than expected in the
      older group. Most elderly patients suffered other diseases, and care was required
      in the administration of steroids. CONCLUSION: The clinical features of elderly
      patients with UC were similar to those of younger patients. However, It should be
      considered that elderly patients often have complications requiring care in the
      use of steroids.

PMID- 17233464
TI  - [Correlates of change in cognitive function during a two-year follow-up period in
      a comprehensive health examination for the community-dwelling elderly for the
      prevention of geriatric syndromes and bed-ridden state].
AB  - PURPOSE: We explored correlates of change in cognitive function during a two-year
      follow-up period among the community-dwelling elderly in Japan, using a
      population-based prospective approach. METHOD: The participants analyzed in the
      present study were 260 men and 222 women aged 70 to 84 years at baseline, living
      in an urban Japanese community. Data such as change in cognitive function during
      two years (calculated by subtracting baseline Mini-Mental State Examination
      [MMSE] score from follow-up MMSE score: a negative value means a decrease in MMSE
      scores during the two-year period) as an outcome variable, age, education,
      hearing and vision problems, IADL deficit (measured by the Tokyo Metropolitan
      Institute of Gerontology of Index of Competence), problems related to memory
      complaint, living alone, hemoglobin level, as explanatory variables, and the
      baseline MMSE score, depressive status (measured by the Mini-International
      Neuropsychiatric Interview), chronic conditions (hypertension, stroke, and
      diabetes mellitus) as covariates, were collected during a comprehensive health
      examination survey for the elderly. RESULTS AND CONCLUSION: We conducted
      multivariate regression analysis by genders to explore correlates of change in
      cognitive function. The results showed that higher age (beta = -0.18), presence
      of hearing problem (beta = -0.21), presence of IADL deficit (beta = -0.15), and
      memory complaint (beta = -0.20) in men, and higher age (beta = -0.27), low
      education level (beta = -0.25) and lower hemoglobin level (beta = 0.16) in women,
      were significantly associated with change in cognitive function when adjusting
      for the potential confounders. These factors may be reliable predictors for
      cognitive decline.

PMID- 17233465
TI  - [The evaluation of the relationships between physical factors and effects of
      exercise intervention on physical functions in community-dwelling older people].
AB  - AIM: It is necessary to determine the effect of exercise on each individual in
      order to target a person for an exercise regimen intended to prevent specific
      health defects in the elderly. The purpose of this study was to evaluate the
      relationship between physical conditions and changes in functional measurements
      after exercise intervention. METHODS: Two hundred seventy-six subjects aged 60
      years and older practiced exercise intervention for three months. The
      measurements were maximal walking speed, one-leg standing with eyes opened or
      closed, functional reach test, timed up and go test, sit and reach, handgrip
      strength, and knee extensor strength. We evaluated the associations between
      physical measurements and changes in functional measurements. RESULTS: Except for
      one-leg standing with eyes closed, all measurements of physical function were
      significantly improved after exercise intervention. The changes in functional
      measurements showed significant negative correlations with the initial physical
      performance measurements, except for maximal walking velocity. CONCLUSIONS: These
      results provided valuable information on more effective strategies for improving
      or maintaining physical functions of community-dwelling older people.
      Comprehensive approaches that adapt the methods of training to the fitness level
      of each subject are needed to effectively improve the physical function of older
      people.

PMID- 17233466
TI  - [Pictures in clinical hematology: Pyothorax-associated lymphoma (PAL)].

PMID- 17233467
TI  - [Mechanism of leukemogenesis by human T-cell leukemia virus type I: from
      infection with HTLV-I to the onset of adult T-cell leukemia].

PMID- 17233468
TI  - [Clinical and hematological characteristics of adult T-cell leukemia/lymphoma].

PMID- 17233469
TI  - [Current status and problem of platelet transfusion for hematopoietic diseases:
      results from a questionnaire survey].
AB  - We carried out a survey on platelet transfusions performed in hospitals certified
      by the Japanese Society of Hematology. The average values of the pretransfusion
      platelet count (trigger value) for the day on which the transfusion was ordered,
      and the values on each day in the interval between the order and actual
      transfusion, were compared with the Guidelines. The average trigger value in
      aplastic anemia and myelodysplastic syndrome patients (A group) (1.41 x
      10(4)/microl) for the same day on which the transfusion was ordered was higher
      than the Guideline, whereas those patients with hematological disorders
      undergoing chemotherapy (B group) and hematopoietic stem cell transplantation (C
      group), namely 2.08 x 10(4)/microl and 2.1 x 10(4)/microl, respectively, were
      acceptable values when compared with the Guidelines. On the other hand, in all
      groups, the transfusion trigger values at one or two days after ordering were
      higher than the Guidelines, being 2.56 x 10(4)/microl in the A group, 3.15 x
      10(4)/microl in the B group, and 2.59 x 10(4)/microl in the C group. We have
      tried to formulate platelet count criteria for ordering a transfusion based on
      one day before the actual transfusion, because these platelet counts on ordering
      were relatively high. The criteria are 1.0-1.5 x 10(4)/microl in group A, 3.0 x
      10(4)/microI in group B, and 3.0 x 10(4)/microl in group C. In order to perform
      platelet transfusion according to the Guidelines, the platelet count on ordering
      should be decreased as we proposed.

PMID- 17233470
TI  - [Lung injury associated with bortezomib therapy in relapsed/refractory multiple
      myeloma in Japan: a questionnaire-based report from the "Lung Injury by
      Bortezomib" Joint Committee of the Japanese Society of Hematology and the
      Japanese Society of Clinical Hematology].
AB  - Bortezomib is a proteasome inhibitor that can be effective in the treatment of
      refractory and relapsed multiple myeloma. Recently, severe pulmonary
      complications associated with bortezomib therapy have been reported in Japan.
      Because bortezomib has not yet been approved for general use in Japan and is
      imported by attending physicians on the request of patients, The Japanese Society
      of Hematology and The Japanese Society of Clinical Hematology sent urgent
      questionnaires to the councilors of both societies in order to explore the
      situation and details of pulmonary complications associated with bortezomib
      therapy. Clinical details were available for 46 patients who had been treated
      with personally imported bortezomib in Japan. Seven patients (15.2%), including 3
      who died from respiratory failure, showed complications definitely or probably
      caused by bortezomib. Of the 7 patients, 6 had a prior history of stem cell
      transplantation (SCT), whereas only 14 of 39 patients without lung injury had
      received SCT treatment (p = 0.033 by Fischer's exact test). Multivariate analysis
      revealed that the concomitant use of corticosteroids might reduce the risk of
      lung injury (p = 0.024; odds ratio = 0.055) and that a previous SCT might
      increase the risk (p = 0.042; odds ratio = 13.140). We summarized these data from
      questionnaires for a limited Japanese cohort and therefore do not know the
      precise incidence of lung injury linked to fatal progression. Thus, future
      verification concerning these matters is warranted after the approval of
      bortezomib for use in Japan. Clinicians should be aware of the possibility of
      severe pulmonary complications associated with bortezomib therapy. Note that this
      report has the same contents as the article appeared in the International Journal
      of Hematology (vol. 84, p406-412, 2006) by permission of both the editorials of
      the Japanese Society of Hematology and the Japanese Society of Clinical
      Hematology, and should be considered as the Japanese translation of the article.

PMID- 17233471
TI  - [Rituximab provided long-term remission in a patient with severe thrombotic
      thrombocytopenic purpura refractory to plasma exchange].
AB  - We report a patient with severe thrombotic thrombocytopenic purpura (TTP)
      refractory to plasmapheresis who was successfully treated with rituximab. A 57
      year-old male patient was referred to our department for further differential
      diagnosis and treatment of anemia and severe thrombocytopenia. Progressive
      psychoneurotic symptoms, hemolytic anemia, thrombocytopenia, renal function
      insufficiency and fever led us to the diagnosis of TTP. ADAMTS13 activity was
      below 3% and an inhibitor for ADAMTS13 was detected. Treatment with
      plasmapheresis and high-dose steroid was initiated but without clinical benefit.
      Two weeks following the initiation of plasmapheresis, we decided to treat the
      patient with 7 cycles of rituximab. No severe rituximab-related adverse effects
      were observed. After treatment with rituximab, the disease remitted, and the
      ADAMTS13 activity level increased. The patient has remained in complete remission
      for more than 1 year. Our data suggest that rituximab may be the optimal
      immunosuppressive therapy for refractory thrombotic thrombocytopenic purpura
      caused by an anti-ADAMTS 13 inhibitor.

PMID- 17233472
TI  - [Superior sagittal sinus thrombosis during remission induction therapy for acute
      lymphoblastic leukemia].
AB  - Superior sagittal sinus thrombosis (SSST) has been reported to be caused by
      coagulopathy following oral contraceptive therapy, DIC, infection around the
      sinus, compression from a tumor, infiltration of tumor, and an inherited
      deficiency of proteins C and S, but SSST associated with hematological
      malignancies and L-asparaginase (L-Asp) therapy is rare. We report a case of an
      adult patient with acute lymphoblastic leukemia (ALL) who developed SSST during
      the remission induction therapy. A 25-year-old man was admitted with left facial
      nerve palsy and, following bone marrow aspiration and lumbar puncture, he was
      diagnosed as having T-ALL with CNS involvement. He received a 1-AdVP regimen as
      remission induction therapy and intrathecal administration of methotrexate and
      cytarabine. On day 29, he had a generalized convulsion and SSST was demonstrated
      by imaging tests. Lymphoid malignancy (ALL in particular), the use of L-Asp, CNS
      involvement, and intrathecal chemotherapy might be risk factors for the
      occurrence SSST. When a patient with those factors develops any neurological
      symptoms, we should pay attention to the occurrence of SSST, as well as stroke or
      CNS involvement, though SSST is rare.

PMID- 17233473
TI  - [Myelodysplastic syndrome with cyclosporine A-induced encephalopathy presenting
      with a mass effect on the right basal ganglia after cord blood transplantation].
AB  - An 18-year-old female with myelodysplastic syndrome underwent an allogeneic cord
      blood transplantation in May 2005. The conditioning regimen consisted of total
      body irradiation, cytarabine and cyclophosphamide. The day of the cord stem cell
      transfusion was counted as Day 0. For acute GVHD prophylaxis, cyclosporine A
      (CsA) and methotrexate were used. Engraftment was achieved on Day 30, acute GVHD
      grade II developed on Day 45 and treatment with methylprednisolone for acute GVHD
      was started. On Day 68 the patient had generalized seizures accompanied by loss
      of consciousness, hypertension and left hemiparesis, and was intubated. A cranial
      CT scan showed a mass effect on the right basal ganglia, and high signal
      intensities on the T2-weighted and FLAIR images of a MR examination were detected
      in the bilateral basal ganglia and posterior lobes, the findings of which were
      compatible with a brain tumor or infectious disease. Since an increased level of
      apparent diffusion coefficient (ADC) values on the bilateral basal ganglia was
      noted, we suspected that vasogenic edema had caused the mass effect. She went
      into remission immediately after CsA treatment was discontinued. Therefore, this
      case was diagnosed as atypical reversible posterior leukoencephalopathy syndrome
      (RPLS) associated with CsA. CsA-induced encephalopathy presenting a mass effect
      in clinical imaging findings is very rare, and an ADC map may be useful for the
      diagnosis of RPLS.

PMID- 17233474
TI  - [Structural organization, functions and dynamics of nuclear pores].
AB  - This review summarized data on the morphological and biochemical analysis of
      nuclear pore complexes, which are complex organelles providing the route of
      passive and active nuclear-cytoplasmic transport to different molecules in the
      eukaryotic cell. The morphology and functional role of nuclear pores in higher
      and lower eukaryotes, and molecular aspects of the import and export of molecules
      from the nucleus are described in addition to factors involved in the regulation
      of these process. Special attention has been paid to sequential steps of the
      nuclear pore assembly in vitro and in vivo.

PMID- 17233475
TI  - [Regulation of morphologicaland functional properties of astroglial cells by
      hydrogen peroxide].
AB  - Effects of hydrogen peroxide on morphological characteristics, proliferation
      index, menadione-dependent lucigenin-enhanced chemiluminescence of C6 glioma
      cells were studied. It was established that H2O2 at 1 x 10(-8) - 5 x 10(-7) M
      concentrations acts as a regulator of morphological and functional properties of
      astrocytes by inducing their reactivation that is manifested as a cell body
      hypertrophy and an increase of proliferative activity and of menadione-dependent
      production of superoxide (O2- ). Cytodestructive action of hydrogen peroxide at a
      concentration higher than 1 microM on C6 glioma cells shows itself as a decrease
      of their proliferation index and the ability to generate O2- under menadione
      action. Using lipopolysaccharide B as a functional stimulator it has been shown
      that H2O2 modifies signaling pathways leading to the increase of mitotic activity
      of C6 glioma cells and decreases the yield of lucigenin-enhanced
      chemiluminescence of astrocytes under menadione action to the level of control
      values.

PMID- 17233476
TI  - [Microtubules are necessary for lamellae retraction of Vero cells].
AB  - Behavior of Vero cells under the 2,3-butaneodione monoxime (BDM) treatment was
      examined using video-microscopy with contrast enhancement. After addition of BDM
      to the culture medium the area of cell contact with substratum gradually reduced-
      within 5 min of treatment cell lamellae became thicker, after 60 min the cell
      area decreased approximately 70 %, and the cells became nearly rounded. At the
      same time actin bundles (stress fibers) depolymerized, and microtubule network
      became denser. Partial depolymerization of microfilaments by treatment with
      latrunculin B at a concentration of 5 nM resulted in complete loss of stress
      fibers, yet cells slightly change their form, and microtubule system remained the
      same as in the control cells. However, after addition of BDM in the presence of
      latrunculin B cells retracted their lamellae more quickly then under BDM sole
      treatment. To evaluate the role of microtubules in the process of cell retraction
      we depolymerized them with nocodazole taken at the concentration of 5 ng/ml.
      Under nocodazole treatment the cell area decreased approximately 20 %, and stress
      fibers became more thick and abandon. The cells did not change their form, and
      stress fibers depolymerized very slowly under BDM treatment in the absence of
      microtubules. After 1 h of BDM treatment in the presence ofnocodazole stress
      fibers were still more numerous than in the control cells. Complete
      depolymerization of stress fibers happened in 90 % of cells only in 24 h after
      addition of BDM. When nocodazole had been washed out of the culture medium in the
      presence of BDM, lamellae started shrinking in 6 min. This time corresponds to
      the time required for the partial restoration of microtubule system. On the bases
      of the results obtained we conclude that retraction of the lamellae in Vero cells
      is guided rather mainly by microtubules, than stress-fibers.

PMID- 17233477
TI  - [ABA accumulation and distribution during the leaf tissues shows its role
      stomatal conductance regulation under short-term salinity].
AB  - The regulative role of ABA in the rapid plant stomatal reactions in response to
      salinity was investigated. The influence of the short-term salinity on the
      overall ABA accumulation and its distribution within the mature leaf (revealed by
      immunohystochemical technique) and stomatal conductance of barley (Hordeum
      vulgare L.) were determined. Rapid bulk leaf ABA accumulation and increase in ABA
      immunolabeling in the mesophyl and guard cells of stomata were shown. The bulk
      ABA increasing in mature barley leaves coincided with stomatal closure induced by
      salt treatment indicating on the ABA contribution to the rapid stomatal closure.

PMID- 17233478
TI  - [The filamin in cell signaling].
AB  - This review describes structure and functions of the group of actin-binding
      proteins--the filamins. Up-to-date facts demonstrate that filamis take part in
      different regulatory processes in the cell. The filamins have diverse functions-
      organization of actin polymers into orthogonal networks (three-dimensional
      scaffolding), attachment of actin filaments to transmembrane receptors,
      regulation of actin-myosin interaction, regulation of actin assembly. In addition
      to its main role of the cytoskeleton structural protein, filamin can serve as
      scaffold protein for formation of signal proteins complexes. One interacts with
      transcription factors and takes part in signal transduction from cytoplasmic
      membranes to the nucleus. C-terminal end of filamin interacts with androgen
      receptor and through cleavage by calpain translocates to the nucleus. Analysis of
      reviewed experimental dates suggests the conception that intracellular
      signalization mediated by cytoskeleton proteins is connected with reorganization
      of the cytoskeleton.

PMID- 17233479
TI  - [Dynamic of DNA-binding activity of transcription factors in A431 cells during
      their spreading on immobilized ligands].
AB  - Dynamics of actin cytoskeleton in A431 cells and specific NF-kappaB SRF and AP-1
      DNA-binding activities were studied during a 2 h spreading of these cells on
      fibronectin, laminin-2/4 or an antibody to epidermal growth factor receptor. Cell
      spreading was shown to be accompanied by sequential formation of actin
      cytoskeleton structures, whose spatial organization depends on the type of
      immobilized ligand. We have determined the time intervals, within which certain
      forms of cytoskeleton do not change qualitatively and are specific for dominant
      part of cell population. It has been shown that DNA-binding activities of the
      above transcription factors studied oscillate during cell spreading. The cycles
      of DNA-binding activity were found to be equel to 15-40 min. The character of
      oscillations depends on both transcription factor and ligand type. The temporal
      comparison of presses of actin cytoskeleton formation and DNA-binding activity of
      NF-kappaB and SRF times suggest that actin cytoskeleton reorganization may be
      presumably associated with activation of NF-KppaB and SRF.

PMID- 17233480
TI  - [Conformation of the HIV-1 gp120 V3 loop. Structure functional analysis of the
      HIV-Haiti viral strain].
AB  - The structural model describing the conformational preferences of the HIV-Haiti
      gp120 V3 loop in geometric space of dihedral angles was generated in terms of NMR
      spectroscopy data using the methods of computer modeling. The elements of
      secondary structure anti conformations of irregular stretches were deciphered for
      the fragment making the virus principal neutralizing determinant as well as the
      determinants of cell tropism and syncytium formation. The structurally conserved
      amino acids of the HIV-1 V3 loop, that may present the forward-looking targets
      for AIDS drug design, were identified based on the combined analysis of the
      results obtained with those derived previously. In particular, it was
      demonstrated that the register of these amino acids comprises Asn-25 critical for
      virus binding with primary cell receptor CD4 as well as Arg-3 critical for
      utilization of CCR5 coreceptor and heparan sulfate proteoglycan syndecans. The
      results obtained are discussed in conjunction with the literature data on the
      biological activity of individual amino acid residues of the HIV-1 gpl20 V3 loop.

PMID- 17233481
TI  - [Retarded excision of pyrimidine dimers in human unstimulated lymphocytes].
AB  - Using immuno-labelling of cyclobutane pyrimidine dimers (CPDs) in nuclei of
      peripheral lymphocytes after their UVC-irradiation and cultivation, we have found
      that within the first four hours of cultivation the CPD-specific fluorescent
      signal from cell nuclei increased. Earlier, a similar increase in binding of
      antibody specific for pyrimidine (6-4) pyrimidone photoproducts to undenatured
      DNA isolated from UV-irradiated Chinese hamster ovary cells was reported
      (Mitchell et al., 1986). Our experiments showed that nucleotide excision repair
      enzyme might induce such of DNA modification in lymphocyte nuclei that increased
      specific antibody binding to DNA fragments with lesions. We suggest that
      enzymatic formation of open structures in DNA predominated qualitatively over
      dual-incision and excision of these fragments, and resulted in the enhanced
      exposure of the pyrimidine dimers in nuclei to specific antibodies. The results
      evidence that nucleotid excision repair in unstimualted human lymphocytes being
      deficient in dual incision and removal of UV-induced DNA lesions appear to be
      capable of performing chromatin relaxation and pre-incision uncoiling of DNA
      fragments with lesions.

PMID- 17233482
TI  - [Workshop: "modern confocal microscopes "Leica" and their application in
      biology"].

PMID- 17233483
TI  - How do you reduce workplace stress for staff and physicians?

PMID- 17233484
TI  - Calling in sick.

PMID- 17233485
TI  - Physician reimbursement under fire.

PMID- 17233486
TI  - No substitute for hard work.

PMID- 17233487
TI  - Prudent purchasing. An eight-step EHR evaluation.

PMID- 17233488
TI  - Where are you, Marcus Welby, MD? Recognize and respond to threats to
      professionalism.

PMID- 17233489
TI  - Don't be shy about retiring.

PMID- 17233490
TI  - Goin' fishin'. 10 points to help you lure good employees.
AB  - A medical practice's people are its most important asset. Regardless of how well
      a group is organized and financed, achieving its strategic goals depends on
      careful recruitment and retention of good employees. Here are 10 points to follow
      when hiring that can smooth the process and help ensure that you get the best
      people for the jobs.

PMID- 17233491
TI  - For love of the profession.
AB  - Outstanding leaders and innovative medical organizations are rare and valuable-
      and models for the rest of us. The Medical Group Management Association and its
      standard-setting and certification body, the American College of Medical Practice
      Executives, annually bestow awards on exceptional contributors to the medical
      practice industry. Read about the 2006 award recipients.

PMID- 17233492
TI  - How much does it cost? Physician pricing in the era of consumerism.
AB  - Setting physician pricing--whether based on actual costs, historical charges or
      current competitive forces--faces new challenges. The new consumerism in health
      care has led to a larger retail market. Patients increasingly pay physicians
      directly for their services, and the role of third-party payers has changed, if
      not diminished. Two types of self-pay patients are growing in number, and the
      challenges to physician pricing strategies are, too.

PMID- 17233493
TI  - [Are the clinical pathways adapted to orthopedics-traumatology?].

PMID- 17233494
TI  - [Gait disorders and lower leg deformities in children].
AB  - Gait disorders and lower legs deformities in children are frequent causes of
      parental concern and of medical advice. These deformities should be analysed
      systematically as well as their consequences for daily activities. We should
      define precisely type, localisation and importance of the deformity: femoral or
      tibial torsion, knock knees, bow legs. The evaluation should always be done
      according to age of the child because these deformities are most often a step
      toward adult morphotype. Sometimes they could be the manifestation of some
      generalised or localised pathology that should be investigated and treated.
      Nevertheless patience and explanations, regular follow-up allow to reassure the
      parents. There is in the great majority of case no place for any conservatrice
      and especially surgical treatment for theses disorders spontaneously healing in
      95% of cases.

PMID- 17233495
TI  - [The Legg-Calve-Perthes disease: which assessment? Which therapeutic approach?].
AB  - Legg-Calve-Perthes disease remains indefinite from an etiologic point of view and
      unforeseable in its evolution. The evolution depends on the extent of epiphyseal
      involvement and the age of the child. It may safely be stated that the more
      extensive the epiphyseal involvement, the more compromised is the prognosis. Also
      the older the child, the more the femoral head remoulding will be limited.
      Preserving articular mobility and containing the head within the depth of
      acetabulum constitute the mainstay of treatment aiming for a femoral head as
      spherical as possible upon completion of growth. At the end of growth spherical
      or ovoid heads will cause no or few problems, however strongly deformed femoral
      heads will evolve into early hip arthritis. The early recognition of which hip
      will profit from which treatment, constitutes the major difficulty of the
      therapeutic process.

PMID- 17233496
TI  - [Indications to complementary radiological exams for pathologies of the
      shoulder].
AB  - Plain Xrays should stay in pole position for the evaluation of shoulder's
      pathologies. They allow frequently to make a diagnosis of the lesion. Indications
      to complementary exams are well established. CT-scan and MRI have to give
      responses to precise questions, which then will permit to manage the treatment.
      CT-scan allows to evaluate accurately bone structures. It is very useful for
      analysing complex fractures of the proximal humerus. It allows also to evaluate
      the amount of glenoid wear to correct before implanting a prosthesis. Arthro-MRI
      is used to study soft tissues, cartilage and bone. Therefore, it is the first
      choice exam to evaluate the rotator cuff tendons, as well as the labrum and
      ligaments in case of shoulder instability.

PMID- 17233497
TI  - [Wrist pain].
AB  - Acute or chronic wrist pain is a relatively frequent complaint that may involve
      all age groups. The pain may be of osseous, articular, periarticular, neurologic,
      vascular origin, or be referred from the cervical spine, shoulder or elbow. The
      diagnosis should be oriented by a precise history and clinical examination. More
      specialised exams will be required according to clinical findings. Psychosocial
      and environmental influences need to be taken into consideration.

PMID- 17233498
TI  - [Septic arthritis (non gonococcal) of the adult: practical aspects].
AB  - Septic arthritis is potentially a life-threatening disease and frequently
      afflicts the most fragile patients. It is crucial to rule-out this diagnosis in a
      patient presenting with monoarticular arthritis, and the gold-standard is
      aspiration of the joint. A primary site of infection such as endocarditis or
      spondylodiscitis must be excluded by appropriate examination and investigative
      studies. The usual infecting organisms causing septic arthritis are
      Staphylococcus and Streptococcus species, and in young adults Gonococcus must be
      considered. Antibiotics should be started promptly after obtaining joint fluid
      for bacteriologic studies. Efficient drainage and lavage of the joint should be
      performed without delay because articular cartilage can be damaged quickly.
      Arthroscopy is a well-accepted technique in treating septic arthritis,
      particularly when the knee is involved.

PMID- 17233499
TI  - [Surgical treatment of radicular pain using minimally invasive techniques].
AB  - Radicular pain can be caused by disc herniation, lateral stenosis, isthmic
      spondylolisthesis with foraminal stenosis, or foraminal encroachment due to
      asymmetrical disc degeneration or scoliosis. Surgery is indicated following
      failure of conservative treatment. Minimally invasive discectomy is indicated for
      subjects presenting with radicular pain with or without neurological deficit and
      appropriate sized herniation in MRI. It offers equivalent efficacy but quicker
      recovery than microdiscectomy. Minimally invasive fusion is indicated for
      radicular pain due to foraminal compression in isthmic spondylolisthesis,
      asymmetric disc degeneration or scoliosis. It allows decrease in blood loss and
      postoperative pain. A less invasive technique should nevertheless not replace
      properly conducted conservative treatment.

PMID- 17233500
TI  - [No-one is expected to ignore... that health care professionals move freely
      between Switzerland and the European Union].

PMID- 17233501
TI  - [Globalization and mental health].

PMID- 17233502
TI  - [Five-hundred million dollars offered to fight against H5N1 in Africa].

PMID- 17233503
TI  - [Urgent: storm on "Telethon"].

PMID- 17233504
TI  - [Foul humidity smell on French soil].

PMID- 17233505
TI  - [Very premature infants and medical relentlessness: the Anglican Church does not
      say no anymore].

PMID- 17233506
TI  - [A huge prank].

PMID- 17233507
TI  - Stroke center certification: a beginning, not an end.

PMID- 17233508
TI  - An ethical dilemma involving a Shy-Drager patient: a case study.
AB  - Shy-Drager syndrome, one type of multisystem atrophy, is considered a Parkinson's
      plus syndrome. Survival time is less than a decade from the onset of symptoms,
      and patients usually become physically dependent and wheelchair bound years
      before death. Ethical dilemmas are very common in health care. In many cases, an
      ethics consultation is required to resolve complex issues. The ethics committee
      is guided toward a decision by application of universal ethical principles.
      Nurses can serve as a patient's advocate, as they are the ones providing direct
      care and forming relationships with the patient. In many cases, conversations
      between nurse and patient become pertinent information the ethics team can use to
      resolve ethical dilemmas.

PMID- 17233509
TI  - The neuroscience nursing 2005 role delineation study: implications for
      certification.
AB  - A task force appointed by the American Board of Neuroscience Nursing conducted a
      role delineation study to define current practice in neuroscience nursing. The
      results were used to validate the content matrix for future Certified
      Neuroscience Registered Nurse (CNRN) examinations. The study employed a survey
      design for which the Nursing Intervention Classification taxonomy was the guiding
      theoretical framework. The eligible sample included all current CNRNs and all
      members of the American Association of Neuroscience Nursing. An invitation to
      participate in an online survey was successfully emailed to 2,462 neuroscience
      nurses; the survey was completed by 477 respondents. They rated the performance
      and importance of 175 neuroscience nursing activities. On the basis of data
      analysis conducted by Schroeder Measurement Technologies, Inc., the task force
      recommended revisions to the CNRN examination matrix to reflect current practice
      in neuroscience nursing.

PMID- 17233510
TI  - Nonspecific behaviors as early indications of cerebral vasospasm.
AB  - This study investigated nonspecific behaviors as early indications of vasospasm
      following subarachnoid hemorrhage. Although symptoms of vasospasm (e.g., lowered
      level of consciousness, focal deficits such as hemiplegia or aphasia), are well
      recognized, the significance of early appearance of nonspecific symptoms such as
      restlessness, unusual behaviors, and impulsive behavior has not been investigated
      in detail. The study design included descriptive quantitative elements and a
      small qualitative component. Nonspecific behaviors were recorded, and the
      prevalence of those behaviors in individuals developing vasospasm was noted. Of
      60 participants, 31 developed vasospasm; 24 of the 31 initially presented with
      nonspecific behaviors (p < .0001). Early detection of cerebral vasospasm allows
      prompt intervention and treatment, with the goal of preventing further ischemia
      or infarction.

PMID- 17233511
TI  - Optimizing patient care in the pediatric epilepsy monitoring unit.
AB  - In the pediatric epilepsy monitoring unit (PEMU) of a large midwestern hospital,
      patient care is optimized through the design of the unit, nurse and family
      education, communication, and medication administration. Four years after the
      PEMU was developed, the hospital held multidisciplinary discussions and surveyed
      nurses working in the PEMU to identify areas of nursing confidence. On the basis
      of the findings, the hospital refined some aspects of patient care, implemented
      an educational program for nurses who work in the PEMU, and established of a core
      group of PEMU nurses. Descriptions of the education and communication procedures
      and of the design features introduced to provide optimal patient care may be
      useful to other facilities seeking to design and implement PEMUs.

PMID- 17233512
TI  - The influence of spirituality on family management of Parkinson's disease.
AB  - This study examined the role of spirituality in defining and managing Parkinson's
      disease (PD) for people with PD and their families. A content-analysis approach
      was used to interpret and analyze individual and family interviews from 27
      families. Participants primarily were Caucasian dyads representing different
      geographic areas and socioeconomic statuses. Findings revealed that the ways
      persons with PD and their families managed the chronic illness were influenced by
      belief and faith, purpose and meaning, prayer, the support of family and friends,
      and hope. Healthcare providers need to understand the role of spirituality in
      influencing ways that persons with PD and their families define and manage the
      disease and to support people in their efforts.

PMID- 17233513
TI  - The influence of metamemory on the quality of life of persons with multiple
      sclerosis.
AB  - This study examined the influence of metamemory (i.e., self-report of memory
      ability and skills), in combination with other factors, on quality of life for
      people with multiple sclerosis (MS). Participants (482 persons with MS) completed
      instruments to measure functional limitations, depressive symptoms, metamemory,
      and perceived quality of life. Participants reported greater satisfaction with
      their memory performance but less frequent use of memory aids and strategies
      compared with 115 older adults on whom the instrument was originally tested.
      Components of metamemory were significantly related to neurological disability,
      duration of disease, depressive symptoms, age, and quality of life. Depressive
      symptoms had a higher impact than other variables in the final regression model
      on quality-of-life prediction.

PMID- 17233514
TI  - Into the unknown: the experiences of individuals living with multiple sclerosis.
AB  - This article examines the narratives of 16 individuals diagnosed with multiple
      sclerosis (MS). Before diagnosis, the participants had experienced disparate and
      transient symptoms. Diagnosis itself involved numerous tests and health
      practitioners, varied responses to the diagnosis, an inability to assimilate
      information about the disease, and a view of MS as being the lesser of two evils.
      Immediately after diagnosis, participants revealed concerns about the
      unpredictable progression of the disease. Patient narratives reflected both
      negative and positive aspects of living with a chronic illness, such as shifting
      roles, discrimination, reevaluation of priorities, reinvestment in the family,
      and positive lifestyle changes. All aspects of the narratives revealed fear and
      anxiety in relation to the unknown.

PMID- 17233515
TI  - Neurological correlates of high-risk behavior: a case study of Alphonse Capone.
AB  - Neurological impairment, traumatic brain injury, and childhood trauma and abuse
      are all associated with violent and high-risk behaviors among prison inmates.
      This case study examines the medical history of a notorious criminal--Alphonse
      Capone. Records suggest an association between Capone's declining neurological
      condition and an increase in high-risk behaviors. Prison, criminal, media, and
      medical records from the National Archives and other sources were studied to
      identify relationships to current research data describing neurological
      abnormalities of prison inmates. Healthcare providers can play a critical role in
      identifying at-risk youths, potentially reducing the incidence of high-risk
      behaviors associated with both crime and infectious disease transmission.

PMID- 17233516
TI  - A study of pupillary assessment in outpatient neurosurgical clinics.
AB  - This study compared the accuracy of three methods of assessing pupil diameter
      Measurements from the ForSite pupillometer and visual assessments were compared
      with measurements obtained using a pupil gauge (the standard method). Two sets of
      measurements were obtained from 65 out-patients at four neurosurgical clinics.
      The correlation between the three methods showed significance; however, the pupil
      gauge measurements showed a more significant correlation with measurements from
      the pupillometer than with visual assessments. Pupil diameter measurements from
      the pupillometer were larger than those from either the pupil gauge or clinical
      observation. We conclude that the ForSite pupillometer is an easy-to-use and
      accurate measure of pupil diameter in a clinic setting. It may be more accurate
      than the pupil gauge.

PMID- 17233518
TI  - A tough year for nursing....

PMID- 17233517
TI  - The pharmacological management of spasticity.
AB  - The spectrum of antispasticity therapies is fairly broad. Familiarity with the
      various therapies will enable a nurse involved in the care of neurological
      patients to deliver the effective treatment and minimize adverse events. Referral
      to specialty care centers may be appropriate for selected patients who require
      more complex interventions for spasticity control.

PMID- 17233519
TI  - "We need to ensure that study days are valuable".

PMID- 17233520
TI  - 'Some trusts are just paying lip service to the protection of their staff'.

PMID- 17233521
TI  - We need to make involvement accessible to the public.

PMID- 17233522
TI  - Are you ready for the 18-week target?

PMID- 17233523
TI  - Transforming lives.

PMID- 17233524
TI  - Changes within the latest draft of the mental health bill.
AB  - The government began its reform of mental health services in 1998. Draft bills
      published in 2002 and 2004 have been controversial. This article looks at the
      latest draft released in November 2006 and how it differs from its predecessors.

PMID- 17233525
TI  - Cardiac monitoring. Part 1--Electrocardiography (ECG).

PMID- 17233526
TI  - Understanding and caring for patients experiencing paranoia.
AB  - Many use the term paranoia in everyday language without understanding the
      condition. For most people who experience paranoia it does not affect their daily
      activities. However, it can be part of a personality disorder and can affect an
      individual's quality of life if not diagnosed and treated appropriately. It is
      important for nurses to have some understanding of the condition and how to help
      these individuals maintain a good quality of life.

PMID- 17233527
TI  - Effect of physical state and particle size distribution on dissolution
      enhancement of nimodipine/PEG solid dispersions prepared by melt mixing and
      solvent evaporation.
AB  - The physical structure and polymorphism of nimodipine were studied by means of
      micro-Raman, WAXD, DSC, and SEM for cases of the pure drug and its solid
      dispersions in PEG 4000, prepared by both the hot-melt and solvent evaporation
      methods. The dissolution rates of nimodipine/PEG 4000 solid dispersions were also
      measured and discussed in terms of their physicochemical characteristics. Micro
      Raman and WAXD revealed a significant amorphous portion of the drug in the
      samples prepared by the hot-melt method, and that saturation resulted in local
      crystallization of nimodipine forming, almost exclusively, modification I
      crystals (racemic compound). On the other hand, mainly modification II crystals
      (conglomerate) were observed in the solid dispersions prepared by the solvent
      evaporation method. However, in general, both drug forms may appear in the solid
      dispersions. SEM and HSM microscopy studies indicated that the drug particle size
      increased with drug content. The dissolution rates were substantially improved
      for nimodipine from its solid dispersions compared with the pure drug or physical
      mixtures. Among solid dispersions, those resulting from solvent coevaporation
      exhibited a little faster drug release at drug concentrations lower than 20 wt%.
      Drug amorphization is the main reason for this behavior. At higher drug content
      the dissolution rates became lower compared with the samples from melt, due to
      the drug crystallization in modification II, which results in higher
      crystallinity and increased particle size. Overall, the best results were found
      for low drug content, for which lower drug crystallinity and smaller particle
      size were observed.

PMID- 17233529
TI  - Endocannabinoid metabolomics: a novel liquid chromatography-mass spectrometry
      reagent for fatty acid analysis.
AB  - We have synthesized 4,4-dimethoxyoxazoline derivatives of several fatty acids
      associated with the endocannabinoid metabolome using
      tris(hydroxymethyl)aminomethane in a 1-step reaction by microwave irradiation.
      The derivatization incorporates a nitrogen into the final product, which allows
      for improved detection by liquid chromatography-mass spectrometry in positive
      atmospheric pressure chemical ionization (APCI) mode. Palmitic and oleic acid
      derivatives show a 200-fold increase in sensitivity compared with the free acids
      when analyzed in negative-mode APCI. In addition to improving sensitivity, the
      oxazoline derivatization creates a similar ionization response for the fatty
      acids tested, which simplifies their quantitation. Fatty acid oxazoline
      derivatives can be detected using the same conditions optimized for the
      endocannabinoids, which allows for a simultaneous quantitation of the entire
      endocannabinoid metabolome.

PMID- 17233530
TI  - Conformational characteristics of the interaction of SR141716A with the CB1
      cannabinoid receptor as determined through the use of conformationally
      constrained analogs.
AB  - Interest in cannabinoid pharmacology increased dramatically upon the
      identification of the first cannabinoid receptor (CB1) in 1998 and continues to
      expand as additional endocannabinoids and cannabinoid receptors are discovered.
      Using CB1 receptor (CB1R) systems, medicinal chemistry programs began screening
      libraries searching for cannabinoid ligands, ultimately leading to the discovery
      of the first potent cannabinoid receptor antagonist, SR141716A (Rimonabant). Its
      demonstrated efficacy in treating obesity and facilitating smoking cessation,
      among other impressive pharmacological activities, has furthered the interest in
      cannabinoid receptor antagonists as therapeutics, such that the number of patents
      and publications covering this class of compounds continues to grow at an
      impressive rate. At this time, medicinal chemistry approaches including
      combinatorial chemistry, conformational constraint, and scaffold hopping are
      continuing to generate a large number of cannabinoid antagonists. These molecules
      provide an opportunity to gain insight into the 3-dimensional structure-activity
      relationships that appear crucial for CB1R-ligand interaction. In particular,
      studies in which conformational constraints have been imposed on the various
      pyrazole ring substituents of SR141716A provide a direct opportunity to
      characterize changes in conformation/conformational freedom within a single class
      of compounds. While relatively few conformationally constrained molecules have
      been synthesized to date, the structure-activity information is often more
      readily interpreted than in studies where entire substituents are replaced. Thus,
      it is the focus of this mini-review to examine the structural properties of
      SR141716A, and to use conformationally constrained molecules to illustrate the
      importance of conformation and conformational freedom to CB1R affinity,
      selectivity, and efficacy.

PMID- 17233528
TI  - NAD metabolism and sirtuins: metabolic regulation of protein deacetylation in
      stress and toxicity.
AB  - Sirtuins are recently discovered NAD(+)-dependent deacetylases that remove acetyl
      groups from acetyllysine-modified proteins, thereby regulating the biological
      function of their targets. Sirtuins have been shown to increase organism and
      tissue survival in diverse organisms, ranging from yeast to mammals. Evidence
      indicates that NAD(+) metabolism and sirtuins contribute to mechanisms that
      influence cell survival under conditions of stress and toxicity. For example,
      recent work has shown that sirtuins and increased NAD(+) biosynthesis provide
      protection against neuron axonal degeneration initiated by genotoxicity or
      trauma. In light of their protective effects, sirtuins and NAD(+) metabolism
      could represent therapeutic targets for treatment of acute and chronic
      neurodegenerative conditions. Our work has focused on elucidating the enzymatic
      functions of sirtuins and quantifying perturbations of cellular NAD(+)
      metabolism. We have developed mass spectrometry methods to quantitate cellular
      NAD(+) and nicotinamide. These methods allow the quantitation of changes in the
      amounts of these metabolites in cells caused by chemical and genetic
      interventions. Characterization of the biochemical properties of sirtuins and
      investigations of NAD(+) metabolism are likely to provide new insights into
      mechanisms by which NAD(+) metabolism regulates sirtuin activities in cells. To
      develop new strategies to improve cell stress resistance, we have initiated proof
      of concept studies on pharmacological approaches that target sirtuins and NAD(+)
      metabolism, with the goal of enhancing cell protection against genotoxicity.

PMID- 17233531
TI  - Insights into the effects of hyperlipoproteinemia on cyclosporine A
      biodistribution and relationship to renal function.
AB  - The purpose of this study was to assess the effect of hyperlipoproteinemia on the
      biodistribution of cyclosporine A (CyA), an extensively lipoprotein bound
      immunosuppressant, in a rat model and to determine the potential toxicological
      significance of this effect. Normolipidemic and hyperlipoproteinemic rats were
      given a single 5 mg/kg dose of CyA as intravenous bolus and at selected times
      postdose, tissues, blood, and plasma were harvested and assayed for CyA content.
      Hyperlipoproteinemia was induced by intraperitoneal injection of 1 g/kg poloxamer
      407. Compared with normolipidemic animals, hyperlipoproteinemic rats had higher
      plasma, blood, kidney, and liver CyA concentrations. In contrast, in heart and
      spleen the concentrations were decreased in hyperlipoproteinemia. The nephrotoxic
      effect of CyA was also evaluated in normolipidemic and hyperlipoproteinemic rats
      after 7 days of dosing with 20 mg/kg/day. In both groups of animals, repeated
      doses of CyA were associated with equivalent decreases in creatinine and urea
      clearances compared with matching control and predose baseline measures. The
      concentrations of drug in kidney were equivalent at the conclusion of the study.
      However, despite these similarities there was microscopic evidence of more severe
      changes in the kidneys in the hyperlipoproteinemic rats, which also experienced a
      significant decrease in body weight compared with the normolipedemic animals. In
      conclusion, the distribution of CyA to kidneys was enhanced in poloxamer 407
      induced hyperlipoproteinemic rats after single doses, and with repeated doses
      there was an apparent greater adverse effect on these animals compared with
      normolipidemic animals.

PMID- 17233532
TI  - Vesicular monoamine transporter 2: role as a novel target for drug development.
AB  - In the central nervous system, vesicular monoamine transporter 2 (VMAT2) is the
      only transporter that moves cytoplasmic dopamine (DA) into synaptic vesicles for
      storage and subsequent exocytotic release. Pharmacologically enhancing DA
      sequestration by VMAT2, and thus preventing the oxidation of DA in the cytoplasm,
      may be a strategy for treating diseases such as Parkinson's disease. VMAT2 may
      also be a novel target for the development of treatments for psychostimulant
      abuse. This review summarizes the possible role of VMAT2 as a therapeutic target,
      VMAT2 ligands reported in the literature, and the structure-activity relationship
      of these ligands, including tetrabenazine analogs, ketanserin analogs, lobeline
      analogs, and 3-amine-2-phenylpropene analogs. The molecular structure of VMAT2
      and its relevance to ligand binding are briefly discussed.

PMID- 17233534
TI  - Quantitative determination of total methamphetamine and active metabolites in rat
      tissue by liquid chromatography with tandem mass spectrometric detection.
AB  - High-throughput liquid chromatography with tandem mass spectrometric detection
      (LC-MS/MS) methodology for the determination of methamphetamine (METH),
      amphetamine (AMP), 4-hydroxymethamphetamine (4-OH-METH), and 4-hydroxyamphetamine
      (4-OH-AMP) was developed and validated using simple trichloroacetic acid sample
      treatment. The method was validated in rat serum, brain, and testis. Lower limits
      of-quantitation (LOQ) for METH and AMP were 1 ng x mL(-1) using positive ion
      electrospray tandem mass spectrometry (MS/MS). The accuracy of the method was
      within 25% of the actual values over a wide range of analyte concentrations. The
      within-assay precision was better than 12% (coefficient of variation). The method
      was linear over a wide dynamic range (0.3-1000 ng x mL(-1)). Quantitation was
      possible in all 3 matrices using only serum standards because of minimal matrix
      associated ion effects or the use of an internal standard. Finally, the LC-MS/MS
      method was used to determine serum, brain, and testis METH and AMP concentrations
      during a subcutaneous infusion (5.6 mg kg(-1) day(-1)) of METH in rats.
      Concentrations of 4-OH-AMP and 4-OH-METH were below the LOQ in experimental
      samples. The bias introduced by using serum calibrators for the determination of
      METH and AMP concentrations in testis and brain was less than 8% and
      insignificant relative to the interanimal variability.

PMID- 17233533
TI  - Endocannabinoid mechanisms of pain modulation.
AB  - Cannabinoids are antinociceptive in animal models of acute, tissue injury-, and
      nerve injury-induced nociception. This review examines the biology of endogenous
      cannabinoids (endocannabinoids) and behavioral, neurophysiological, and
      neuroanatomical evidence supporting the notion that cannabinoids play a role in
      pain modulation. Behavioral pharmacological approaches, in conjunction with the
      identification and quantification of endocannabinoids through the use of liquid
      and gas chromatography mass spectrometry, have provided insight into the
      functional roles of endocannabinoids in pain modulation. Here we examine the
      distribution of cannabinoid receptors and endocannabinoid-hydrolyzing enzymes
      within pain modulatory circuits together with behavioral, neurochemical, and
      neurophysiological studies that suggest a role for endocannabinoid signaling in
      pain modulation. This review will provide a comprehensive evaluation of the roles
      of the endocannabinoids 2-arachidonoylglycerol and anandamide in stress-induced
      analgesia. These findings provide a functional framework with which to understand
      the roles of endocannabinoids in nociceptive processing at the supraspinal level.

PMID- 17233536
TI  - Modeling weight variability in a pan coating process using Monte Carlo
      simulations.
AB  - The primary objective of the current study was to investigate process variables
      affecting weight gain mass coating variability (CV(m) ) in pan coating devices
      using novel video-imaging techniques and Monte Carlo simulations. Experimental
      information such as the tablet location, circulation time distribution, velocity
      distribution, projected surface area, and spray dynamics was the main input to
      the simulations. The data on the dynamics of tablet movement were obtained using
      novel video-imaging methods. The effects of pan speed, pan loading, tablet size,
      coating time, spray flux distribution, and spray area and shape were
      investigated. CV(m) was found to be inversely proportional to the square root of
      coating time. The spray shape was not found to affect the CV(m) of the process
      significantly, but an increase in the spray area led to lower CV(m) s. Coating
      experiments were conducted to verify the predictions from the Monte Carlo
      simulations, and the trends predicted from the model were in good agreement. It
      was observed that the Monte Carlo simulations underpredicted CV(m) s in
      comparison to the experiments. The model developed can provide a basis for
      adjustments in process parameters required during scale-up operations and can be
      useful in predicting the process changes that are needed to achieve the same
      CV(m) when a variable is altered.

PMID- 17233535
TI  - Geldanamycin, an inhibitor of Hsp90, blocks cytoplasmic retention of progesterone
      receptors and glucocorticoid receptors via their respective ligand binding
      domains.
AB  - Steroid hormone receptors (SHRs), such as glucocorticoid receptors (GR) and
      progesterone receptors (PR), are shuttling proteins that undergo continuous
      nuclear import and export. Various mechanisms have been proposed to explain the
      localization of SHRs. It has been suggested that the ligand-binding domain (LBD)
      of SHRs is important in determining the subcellular localization. We have studied
      the localization of GR-LBD and PR-LBD alone, as well as of full-length GR and PR
      in the presence of geldanamycin (GA), a benzoquinoid ansamycin that specifically
      inhibits heat shock protection (Hsp90), using transient transfections and
      fluorescent microscopy. Our studies have indicated that GR-LBD and PR-LBD are
      retained in the cytoplasm via interaction with Hsp90. It was observed that in the
      unliganded state, treatment with GA translocates these LBDs to the nucleus.
      Similar results were obtained for full-length PR and GR. Additionally, it was
      found that after ligand induction, GA accelerated reexport of SHRs after ligand
      washout, implicating Hsp90 in nuclear retention of SHRs in the washout state. We
      also propose that a recently found "export" signal present in the LBD of SHRs is
      involved in interactions with Hsp90 and hence cytoplasmic retention of these
      receptors. After ligand induction, Hsp90 also may play a role in nuclear
      retention of SHRs following hormone washout.

PMID- 17233538
TI  - The effect of drug concentration and curing time on processing and properties of
      calcium alginate beads containing metronidazole by response surface methodology.
AB  - The purpose of present research work was to prepare calcium alginate beads
      containing water-soluble drug metronidazole using 3(2) factorial design, with
      drug concentration and curing time as variables. Curing time was kept as low as
      possible to improve entrapment with increasing drug concentration. Mostly the
      drugs which had been encapsulated were water insoluble to facilitate drug
      encapsulation; a characteristic drug release as whole process is aqueous based.
      Entrapment efficiency was in the range of 81% to 96% wt/wt, which decreased with
      decrease in polymer concentration and increase in curing time. The beads were
      spherical with size range between 1.4 and 1.9 mm. Scanning electron microscope
      (SEM) photomicrographs revealed increase in the leaching of drug crystals with
      increased curing time and high drug concentrations. In acidic environment, the
      swelling ratio was 200% in 30 minutes, but in basic medium, it increased to a
      maximum of 1400% within 120 minutes. In acidic medium, the swelling and drug
      release properties were influenced by drug solubility, whereas in phosphate
      buffer these properties were governed by the gelling of polymer and exhibited
      curvilinear and quadratic functions of both the variables, respectively.

PMID- 17233537
TI  - Anisotropic surface chemistry of crystalline pharmaceutical solids.
AB  - The purpose of this study was to establish the link between the wetting behavior
      of crystalline pharmaceutical solids and the localized surface chemistry. A range
      of conventional wetting techniques were evaluated and compared with a novel
      experimental approach: sessile drop contact angle measurements on the individual
      facets of macroscopic (>1 cm) single crystals. Conventional measurement
      techniques for determining surface energetics such as capillary rise and sessile
      drops on powder compacts were found not to provide reliable results. When the
      macroscopic crystal approach was used, major differences for advancing contact
      angles, theta(a), of water were observed-as low as 16 degrees on facet (001) and
      as high as 68 degrees on facet (010) of form I paracetamol. theta(a) trends were
      in excellent agreement with X-ray photoelectron spectroscopy surface composition
      and known crystallographic structures, suggesting a direct relationship to the
      local surface chemistry. Inverse gas chromatography (IGC) was further used to
      probe the surface properties of milled and unmilled samples, as a function of
      particle size. IGC experiments confirmed that milling exposes the weakest
      attachment energy facet, with increasing dominance as particle size is reduced.
      The weakest attachment energy facet was also found to exhibit the highest
      theta(a) for water and to be the most hydrophobic facet. This anisotropic wetting
      behavior was established for a range of crystalline systems: paracetamol
      polymorphs, aspirin, and ibuprofen racemates. theta(a) was found to be very
      sensitive to the local surface chemistry. It is proposed that the
      hydrophilicity/hydrophobicity of facets reflects the presence of functional
      groups at surfaces to form hydrogen bonds with external molecules.

PMID- 17233539
TI  - Industrially feasible alternative approaches in the manufacture of solid
      dispersions: a technical report.
AB  - The purpose of this report was to compile relevant technical information on
      various alternative strategies that can be used as feasible approaches in the
      development of solid dispersions. The technologies discussed in the report are
      spray coating on sugar beads with a fluidized bed coating system, hot melt
      extrusion, direct capsule filling, electrostatic spinning, surface active
      carriers, and supercritical fluid technology. The focus is on basic principles,
      the equipment involved, and the relevant scale-up work. These technologies have
      been found to eliminate several drawbacks posed by the conventional methods of
      manufacturing of solid dispersions such as laborious preparation methods,
      reproducibility, scaling up of manufacturing processes, stability of drug, and
      vehicle.

PMID- 17233540
TI  - Transdermal delivery of diclofenac sodium through rat skin from various
      formulations.
AB  - The aim of this study was to evaluate and compare the in vitro and in vivo
      transdermal potential of w/o microemulsion (M) and gel (G) bases for diclofenac
      sodium (DS). The effect of dimethyl sulfoxide (DMSO) as a penetration enhancer
      was also examined when it was added to the M formulation. To study the in vitro
      potential of these formulations, permeation studies were performed with Franz
      diffusion cells using excised dorsal rat skin. To investigate their in vivo
      performance, a carrageenan-induced rat paw edema model was used. The commercial
      formulation of DS (C) was used as a reference formulation. The results of the in
      vitro permeation studies and the paw edema tests were analyzed by repeated
      measures analysis of variance. The in vitro permeation studies found that M was
      superior to G and C and that adding DMSO to M increased the permeation rate. The
      permeability coefficients (Kp) of DS from M and M+DMSO were higher (Kp = 4.9 x
      10(-3) +/- 3.6 x 10(-4) cm/h and 5.3 x 10(-3) +/- 1.2 x 10(-3) cm/h,
      respectively) than the Kp of DS from C (Kp = 2.7 x 10(-3) +/- 7.3 x 10(-4) cm/h)
      and G (Kp = 4.5 x 10(-3) +/- 4.5 x 10(-5) cm/h). In the paw edema test, M showed
      the best permeation and effectiveness, and M+DMSO had nearly the same effect as
      M. The in vitro and in vivo studies showed that M could be a new, alternative
      dosage form for effective therapy.

PMID- 17233541
TI  - Investigation of a 2-step agglomeration process performed in a rotary processor
      using polyethylene glycol solutions as the primary binder liquid.
AB  - The purpose of this research was to investigate the use of polyethylene glycol
      (PEG) solutions as the primary binder liquid in a 2-step agglomeration process
      performed in a rotary processor and characterize the resulting granules and their
      tableting characteristics. This was done by granulation of binary mixtures of
      microcrystalline cellulose (MCC) and either lactose, calcium phosphate,
      acetaminophen, or theophylline, in a 1:3 ratio, using a 50% (wt/wt) aqueous
      solution of PEG and water as the binder liquid. Formulations containing lactose
      were agglomerated using 5 different amounts of the PEG binder solution, giving
      rise to a PEG content in the range of 6% to 43% (wt/wt). The process outcome was
      characterized according to adhesion, yield, and water requirement, and the
      prepared granules were characterized according to size, size distribution, and
      flow properties as well as tableting properties. The agglomeration of all
      mixtures resulted in high yields of free-flowing agglomerates and gave rise to
      good reproducibility of the investigated agglomerate characteristics. The process
      allowed for the incorporation of 42.5% (wt/wt) PEG, which is higher than the
      percentage of PEG reported for other equipment. Tablets of sufficient strength
      could be prepared with all investigated excipients using 20% wt/wt PEG; higher
      PEG contents gave rise to adhesion and prolonged disintegration. In conclusion,
      agglomeration in a torque-controlled rotary processor using solutions of PEG as
      the primary binder liquid was found to be a robust process, suitable for the
      incorporation of high contents of PEG and/or drug compounds.

PMID- 17233542
TI  - Evaluation of porous carrier-based floating orlistat microspheres for gastric
      delivery.
AB  - The purpose of this research was to prepare floating microspheres consisting of
      (1) calcium silicate as porous carrier; (2) orlistat, an oral anti-obesity agent;
      and (3) Eudragit S as polymer, by solvent evaporation method and to evaluate
      their gastro-retentive and controlled-release properties. The effect of various
      formulation and process variables on the particle morphology, micromeritic
      properties, in vitro floating behavior, percentage drug entrapment, and in vitro
      drug release was studied. The gamma scintigraphy of the optimized formulation was
      performed in albino rabbits to monitor the transit of floating microspheres in
      the gastrointestinal tract. The orlistat-loaded optimized formulation was orally
      administered to albino rabbits, and blood samples collected were used to
      determine pharmacokinetic parameters of orlistat from floating microspheres. The
      microspheres were found to be regular in shape and highly porous. Microsphere
      formulation CS4, containing 200 mg calcium silicate, showed the best floating
      ability (88% +/- 4% buoyancy) in simulated gastric fluid as compared with other
      formulations. Release pattern of orlistat in simulated gastric fluid from all
      floating microspheres followed Higuchi matrix model and Peppas-Korsmeyer model.
      Prolonged gastric residence time of over 6 hours was achieved in all rabbits for
      calcium silicate-based floating microspheres of orlistat. The enhanced
      elimination half-life observed after pharmacokinetic investigations in the
      present study is due to the floating nature of the designed formulations.

PMID- 17233543
TI  - Engineering bacterial vectors for delivery of genes and proteins to antigen
      presenting cells.
AB  - Bacterial vectors offer a biological route to gene and protein delivery with this
      article featuring delivery to antigen-presenting cells (APCs). Primarily in the
      context of immune stimulation against infectious disease or cancer, the goal of
      bacterially mediated delivery is to overcome the hurdles to effective
      macromolecule delivery. This review will present several bacterial vectors as
      macromolecule (protein or gene) delivery devices with both innate and acquirable
      (or engineered) biological features to facilitate delivery to APCs. The review
      will also present topics related to large-scale manufacture, storage, and
      distribution that must be considered if the bacterial delivery devices are ever
      to be used in a global market.

PMID- 17233544
TI  - Post-herpetic neuralgia in older adults: evidence-based approaches to clinical
      management.
AB  - Many individuals across the globe have been exposed to the varicella-zoster virus
      (VZV) that causes chickenpox. After chickenpox has resolved, the virus remains
      latent in the dorsal root ganglia where it can re-emerge later in life as herpes
      zoster, otherwise known as shingles. Herpes zoster is a transient disease
      characterised by a dermatomal rash that is usually associated with significant
      pain. Post-herpetic neuralgia (PHN) is the term used for the condition that
      exists if the pain persists after the rash has resolved. Advanced age and
      compromised cell-mediated immunity are significant risk factors for reactivation
      of herpes zoster and the subsequent development of PHN. Though the
      pathophysiology of PHN is unclear, studies suggest peripheral and central
      demyelination as well as neuronal destruction are involved. Both the vaccine
      against VZV (Varivax) and the newly released vaccine against herpes zoster
      (Zostavax) may lead to substantial reductions in morbidity from herpes zoster and
      PHN. In addition, current evidence suggests that multiple medications are
      effective in reducing the pain associated with PHN. These include tricyclic
      antidepressants, antiepileptics, opioids, NMDA receptor antagonists as well as
      topical lidocaine (lignocaine) and capsaicin. Reasonable evidence supports the
      use of intrathecal corticosteroids, but the potential for neurological sequelae
      should prompt caution with their application. Epidural corticosteroids have not
      been shown to provide effective analgesia for PHN. Sympathetic blockade may
      assist in treating the pain of herpes zoster or PHN. For intractable PHN pain,
      practitioners have performed delicate surgeries and attempted novel therapies.
      Although such therapies may help reduce pain, they have been associated with
      disappointing results, with up to 50% of patients failing to receive acceptable
      pain relief. Hence, it is likely that the most effective future treatment for
      this disease will focus on prevention of VZV infection and immunisation against
      herpes zoster infection with a novel vaccine.

PMID- 17233545
TI  - Management of gout in older adults: barriers to optimal control.
AB  - Gout, a common inflammatory arthritis, can be diagnosed with absolute certainty.
      Gout results from the body's reaction to urate crystals deposited in tissues, and
      this pathophysiology is well understood. If used appropriately, available
      therapies can be entirely effective in not only treating the symptoms of gout,
      but also in eliminating the excess urate from the body, thereby eradicating the
      disease. Because of these facts, management of patients with gout should be
      successful. However, management of gout is particularly challenging in the
      elderly, even though the principles of management are the same for all age
      groups. The purpose of this article is to review these principles and discuss
      them as they pertain to the elderly. The classic gout attack is acute in onset,
      extremely painful and associated with marked swelling, warmth, erythema and
      tenderness of a single joint. However, the diagnosis of gout may be challenging
      in the elderly because atypical presentations are more common in this group.
      Treatment of acute gout involves the use of NSAIDs, colchicine, corticosteroids
      or corticotropin (adrenocorticotropic hormone). Unfortunately, co-morbid
      conditions such as chronic kidney disease, peptic ulcer disease and congestive
      heart failure may make the use of these agents dangerous or contraindicated.
      Thus, it is important to try to treat an acute flare of gout at the earliest
      sign, because the sooner treatment is initiated, the faster the inflammation will
      resolve. Urate-lowering agents include allopurinol and uricosuric agents. These
      also must be used judiciously in the elderly. However, if used at the lowest dose
      that maintains the serum urate level below 5.0-6.0 mg/dL, the excess urate in the
      body will be eliminated, acute flares will no longer occur and tophi will
      resolve. Gout is often seen in association with hypertension, excessive alcohol
      consumption, obesity and hypertriglyceridaemia. These conditions and the
      medications used to treat them may contribute to the hyperuricaemia. Treating
      these conditions and using medications that do not promote hyperuricaemia will
      aid in the management of gout. Despite the challenges that often complicate the
      management of gout in the elderly, an understanding of the pathophysiology of the
      disease and both the indications and limitations of the medications used should
      allow successful treatment.

PMID- 17233547
TI  - Effects of statins on cognitive function in patients with Alzheimer's disease in
      galantamine clinical trials.
AB  - BACKGROUND AND OBJECTIVE: A number of reports have been published on the possible
      involvement of changes in brain cholesterol metabolism in the origin of
      Alzheimer's disease (AD) and the potential for influencing these changes by
      administration of HMG-CoA reductase inhibitors ('statins'). The aim of this study
      was to evaluate a potential association between use of statins and maintenance of
      cognitive function in patients with AD in galantamine clinical trials. METHOD: A
      post hoc analysis was conducted on data pooled from three double-blind, placebo
      controlled, clinical trials of galantamine in patients with AD. Patients were
      divided into four treatment groups: statin plus galantamine (n = 42), statin
      alone (n = 50), galantamine alone (n = 614) or neither galantamine nor statin (n
      = 619). RESULTS: Galantamine was associated with a significant beneficial effect
      on cognitive status (p < 0.001). The association of use of statins with changes
      in cognitive status was not significant (p = 0.083). There was no significant
      interaction between the effects on cognition of statins and galantamine (p =
      0.183) and no statistically significant changes in adverse effect rates were
      observed. CONCLUSION: These findings suggest the need for larger long-term trials
      to confirm or refute possible effects of statins on cognitive function and the
      potential interaction of statins with acetylcholinesterase inhibitors in the
      treatment of AD.

PMID- 17233546
TI  - Patient adherence to osteoporosis medications: problems, consequences and
      management strategies.
AB  - Adherence to osteoporosis medications is relatively poor. Approximately 20-30% of
      patients taking daily or weekly treatments may suspend their treatment within 6
      to 12 months of initiating therapy. Patients with poor adherence increase their
      risk of osteoporotic fractures and hospitalisation. The majority of patients who
      discontinue therapy appear to do so because of drug-induced adverse effects. Fear
      of adverse effects or other health risks is another commonly cited reason for
      discontinuing therapy. Factors associated with medication adherence include
      fractures, regular exercise, female sex, fewer non-osteoporosis medications and
      co-morbidities, early menopause, willingness to take medications, awareness of
      osteoporosis status based on a diagnostic test, anti-inflammatory therapy and
      corticosteroid therapy. Factors associated with non-adherence include adverse
      effects, pain and being unsure about bone mineral density (BMD) test results.
      Bisphosphonates, a common class of drugs for treating osteoporosis, have specific
      administration requirements (e.g. fasting, remaining upright and not ingesting
      other medications concomitantly). Patient surveys indicate that 12-18% of
      patients report non-compliance with at least one administration rule. Strategies
      to increase adherence include reducing administration frequency to weekly or
      monthly, monitoring patients with bone markers and BMD testing, providing
      adequate instructions, practitioner feedback and support, and educational
      materials and sessions. Future studies are needed regarding strategies to
      increase adherence to osteoporosis medications.

PMID- 17233548
TI  - Elderly medical patients treated with prophylactic dosages of enoxaparin:
      influence of renal function on anti-Xa activity level.
AB  - BACKGROUND: The safety and optimal use of prophylactic treatment with low
      molecular-weight heparins in elderly patients with impaired renal function remain
      undefined. METHODS: The primary aim of this study was to analyse, in 'real life',
      the influence of renal function, as assessed by creatinine clearance (CL(CR)), on
      the level of anti-Xa activity in medical hospitalised elderly patients receiving
      prophylactic dosages of enoxaparin. Consecutive hospitalised acutely ill medical
      patients aged >or=75 years receiving daily dosages of enoxaparin 4000 IU for up
      to 10 days were prospectively enrolled in two centres. Peak anti-Xa activity was
      measured at the beginning and during the course of therapy. RESULTS: One hundred
      and twenty-five patients (31 men, 94 women), mean age 87.5 +/- 6.3 years, mean
      bodyweight 56.4 +/- 11.9 kg and mean CL(CR) 39.8 +/- 16.1 mL/min, were enrolled
      in the study. The mean maximum anti-Xa activity (day 1 to day 10) [anti-Xa(max1
      10)] was 0.64 +/- 0.23 IU/mL (range 0.24-1.50 IU/mL). Weak negative correlations
      were found between CL(CR) and anti-Xa(max) and between bodyweight and anti
      Xa(max). Mean anti-Xa(max) was slightly but significantly higher in patients with
      CL(CR) of 20-30 mL/min compared with patients with CL(CR) of 31-40, 41-50 or 51
      80 mL/min (0.72 versus 0.61, 0.61 and 0.60 IU/mL, respectively), and in patients
      weighing <50 kg compared with patients weighing 50-60 kg or >60 kg (0.74 vs 0.64
      and 0.52 IU/mL, respectively). Serious bleeding occurred in five patients, but
      anti-Xa(max) values in these patients were not different to those in patients
      without bleeding (p = 0.77). Individual anti-Xa(max) at the beginning or during
      the course of treatment was measured in the subgroup of 58 patients in whom anti
      Xa activity was measured at least once during the study. The mean anti-Xa(max)
      value was slightly but significantly higher during the course of the therapy than
      at the beginning of the study (0.63 +/- 0.26 IU/mL vs 0.56 +/- 0.23 IU/mL, p =
      0.012). CONCLUSION: Only CL(CR) <30 mL/min and bodyweight <50 kg were associated
      with significantly higher anti-Xa(max) values. The clinical relevance of these
      increases remains questionable. No conclusions about the safety of enoxaparin in
      elderly medical patients can be drawn from these findings.

PMID- 17233550
TI  - Expression of heat shock protein 70 (HSP70) in patients with colorectal
      adenocarcinoma--immunohistochemistry and Western blot analysis.
AB  - The role of heat shock protein 70 (HSP70) expression has been investigated in
      various types of tumors. There are only little and controversial data about its
      clinical relevance in colorectal carcinoma, one of the most common carcinomas
      observed in humans. In this study we investigated expression of HSP70 in human
      colonic carcinoma and possible correlation with clinicopathology. To assess
      patterns (cytosolic and membrane) of HSP70 expression, the 48 surgically removed
      colorectal adenocarcinomas and 12 normal colonic and rectal mucosal samples were
      examined by immunohistochemistry and Western-blot. According to results of
      immunohistochemistry, expression of cytoplasmic HSP72 was significantly higher in
      colorectal carcinoma compared with normal and adjacent mucosa (p<0.01). In
      addition, there was significant increase in HSP72 expression in lymph node
      positive compared to node-negative group (p<0.001). Dukes C2 stage of colonic
      cancer showed significantly higher immunohistochemical score than Dukes B2 and B1
      stage groups (p< 0.05 i.e. p< 0.02). There was no relation between expression of
      HSP72 and degree of tumor differentiation. Using Western blot analyses, we
      noticed elevated levels of cytosolic HSP70 in colorectal cancer cells compared to
      normal. Densitometric analysis of blots of plasma membrane HSP70 expression has
      shown decrease in colorectal cancer cells compared to normal mucosa. According to
      our results, overexpression of HSP72 in malignant tissues of patients with
      colorectal carcinoma is related to tumor progression, suggesting that these
      proteins could play an important role not only in tumorigenesis but also in the
      development of drug resistance. Further research is necessary to clarify the
      mechanisms responsible for differential HSP70 expression as well as its
      definitive role in colorectal cancer.

PMID- 17233551
TI  - Is FLT3 internal tandem duplication significant indicator for allogeneic
      transplantation in acute myeloid leukemia? An analysis of patients from the Czech
      Acute Leukemia Clinical Register (ALERT).
AB  - To assess the prognostic relevance of activating mutations of FLT3 gene on
      outcome of allogeneic transplantations in AML patients, we performed an analysis
      of all patients with FLT3 mutations registered in the Czech Acute Leukemia
      Clinical Register (ALERT) from 2003 till the end of 2005. Within the mentioned
      period 170 patients with AML of median age 56 years (23-77) were investigated for
      FLT3 mutation, within them 36 cases (21%) with FLT3 mutations (32 FLT3 ITD and 4
      FLT3 D835) were found. Out of FLT3 ITD positive patients 13 had allogeneic
      transplantation, 20 patients with mutations of FLT3 were treated with
      chemotherapy without transplantation. Results of the treatment of these patients
      were compared with the results of the group of patients without FLT3 mutation,
      which was according to other characteristics identical with the group of patients
      with FLT3 mutations (n=134). Median overall survival (OS) was significantly
      shorter for patients with FLT3 ITD (34.8 weeks) than for those without FLT3
      mutations (67.7 weeks; P=0.028). Median OS of patients with FLT3 ITD who had
      allogeneic transplantation was 42.5 weeks; median OS of patients with FLT3 ITD
      treated only with chemotherapy was 29.6 weeks (P=0.362). After allogeneic
      transplantation, median OS of FLT3 mutations negative patients was similar to
      FLT3 ITD positive patients (46.7 versus 42.5 weeks; P=0.443). Our results suggest
      that at present there is no strong evidence that FLT3 status alone should
      influence the decision to proceed to allogeneic transplantation in AML patients.
      Decision to proceed to alogeneic transplantation should not be based on the FLT3
      status only, but it should also consider other prognostic factors.

PMID- 17233553
TI  - Bone matrix formation in osteogenic cultures derived from human embryonic stem
      cells in vitro.
AB  - Bone matrix production and mineralization involves sophisticated mechanisms,
      including the initial formation of an organic extracellular matrix into which
      inorganic hydroxyapatite crystals are later deposited. Human embryonic stem (hES)
      cells offer a potential to study early developmental processes and provide an
      unlimited source of cells. In this study, four different hES cell lines were
      used, and two different approaches to differentiate hES cells into the osteogenic
      lineage were taken. Undifferentiated cells were cultured either in suspension,
      facilitating the formation of embryoid bodies (EBs), or in monolayer, and both
      methods were in the presence of osteogenic supplements. Novel to our osteogenic
      differentiation study was the use of commercially available human foreskin
      fibroblasts to support the undifferentiated growth of the hES cell colonies, and
      their propagation in serum replacement-containing medium. Characterization of the
      osteogenic phenotype revealed that all hES cell lines differentiated toward the
      mesenchymal lineage, because T-Brachyury, Flt-1, and bone morphogenetic protein-4
      could be detected. Main osteoblastic marker genes Runx2, osterix, bone
      sialoprotein, and osteocalcin were up-regulated. Alizarin Red S staining
      demonstrated the formation of bone-like nodules, and bone sialoprotein and
      osteocalcin were localized to these foci by immunohistochemistry. Cells
      differentiated in monolayer conditions exhibited greater osteogenic potential
      compared to those from EB-derived cells. We conclude that in vitro hES cells can
      produce a mineralized matrix possessing all the major bone markers, the
      differentiation of pluripotent hES cells to an osteogenic lineage does not
      require initiation via EB formation, and that lineage potential is not dependent
      on the mode of differentiation induction but on a cell line itself.

PMID- 17233554
TI  - Identification of proteomic changes during differentiation of adult mouse
      subventricular zone progenitor cells.
AB  - The use of neural precursor cells (NPCs) represents a promising repair strategy
      for many neurological disorders. However, the molecular events and biological
      features that control NPC proliferation and their differentiation into neurons,
      astrocytes, and oligodendrocytes are unclear. In the present study, we used a
      comparative proteomics approach to identify proteins that were differentially
      regulated in NPCs after short-term differentiation. We also used a subcellular
      fractionation technique for enrichment of nuclei and other dense organelles to
      identify proteins that were not readily detected in whole cell extracts. In
      total, 115 distinct proteins underwent expression changes during NPC
      differentiation. Forty one of these were only identified following subcellular
      fractionation. These included transcription factors, RNA-processing factors, cell
      cycle proteins, and proteins that translocate between the nucleus and cytoplasm.
      Biological network analysis showed that the differentiation of NPCs was
      associated with significant changes in cell cycle and protein synthesis
      machinery. Further characterization of these proteins could provide greater
      insight into the mechanisms involved in regulation of neurogenesis in the adult
      central nervous system (CNS) and potentially identify points of therapeutic
      intervention.

PMID- 17233556
TI  - Genome wide gene expression studies in mood disorders.
AB  - Microarrays offer the possibility of screening in parallel virtually all genes
      expressed in a given tissue or to study the molecular signature associated with
      available treatments. As such, this technology has been increasingly used to
      investigate multifactorial and polygenic complex traits such as psychiatric
      disorders, in particular, schizophrenia and mood disorders. This review focuses
      on microarray studies investigating mood disorders. Study designs, methodologic
      approaches and limitations, subsequent follow-up strategies, and confirmation of
      results are discussed. Despite the apparent disparate and not always concordant
      results, it appears evident that this technology is a powerful and inevitable
      approach for the study of mood disorders, especially when phenotype-specific
      confounders are properly accounted for. Thus, alterations of mitochondrial,
      oligodendrocyte, and myelin related genes in bipolar disorder, of signaling and
      olidendroglial related genes in depression, and of GABA-glutamate related genes
      in depression and suicide have been observed and have confirmed new avenues for
      the study and the treatment of these complex disorders.

PMID- 17233555
TI  - Gene expression profiling and clinical outcome in breast cancer.
AB  - Pathologic and clinical heterogeneity of breast cancer reflects the poorly
      documented, complex, and combinatory molecular basis of the disease and is in
      part responsible for therapeutic failures. The DNA microarray technique allows
      the analysis of RNA expression of several thousands of genes simultaneously in a
      sample. There are multiple potential applications of the technique in cancer
      research. A number of recent studies have shown the promising role of gene
      expression profiling in breast cancer by identifying new prognostic subclasses
      unidentifiable by conventional parameters and new prognostic and/or predictive
      gene signatures, whose predictive impact is superior to conventional
      histoclinical prognostic factors. In this review we describe current use of DNA
      microarrays in the prognosis of breast cancer. We also discuss issues that need
      to be addressed in the near future to allow the method to reach its full
      potential.

PMID- 17233557
TI  - DNA microarray analyses in higher plants.
AB  - DNA microarrays were originally devised and described as a convenient technology
      for the global analysis of plant gene expression. Over the past decade, their use
      has expanded enormously to cover all kingdoms of living organisms. At the same
      time, the scope of applications of microarrays has increased beyond expression
      analyses, with plant genomics playing a leadership role in the on-going
      development of this technology. As the field has matured, the rate-limiting step
      has moved from that of the technical process of data generation to that of data
      analysis. We currently face major problems in dealing with the accumulating
      datasets, not simply with respect to how to archive, access, and process the huge
      amounts of data that have been and are being produced, but also in determining
      the relative quality of the different datasets. A major recognized concern is the
      appropriate use of statistical design in microarray experiments, without which
      the datasets are rendered useless. A vigorous area of current research involves
      the development of novel statistical tools specifically for microarray
      experiments. This article describes, in a necessarily selective manner, the types
      of platforms currently employed in microarray research and provides an overview
      of recent activities using these platforms in plant biology.

PMID- 17233558
TI  - Microarray studies of gene expression in fish.
AB  - The use of microarrays for the study of various aspects of fish physiology has
      seen a spectacular increase in recent years. From early studies with model
      species, such as zebrafish, to current studies with commercially important
      species, such as salmonids, catfish, carp, and flatfish, microarray technology
      has emerged as a key tool for understanding developmental processes as well as
      basic physiology. In addition, microarrays are being applied to the fields of
      ecotoxicology and nutrigenomics. A number of different platforms are now
      available, ranging from microarrays containing cDNA amplicons to oligomers of
      various sizes. High-density microarrays containing hundreds of thousands of
      distinct oligomers have been developed for zebrafish and catfish. As this
      exciting technology advances, so will our understanding of global gene expression
      in fish. Furthermore, lessons learned from this experimentally tractable group of
      organisms can also be applied to more advanced organisms such as humans.

PMID- 17233559
TI  - The utility of carbohydrate microarrays in glycomics.
AB  - Carbohydrate microarrays are powerful tools in glycomics. Interactions of
      different carbohydrate structures with a wide variety of biological targets,
      including proteins, RNA, viruses, and whole cells, have been investigated using
      this technique. Binding preferences and specificities, inhibition of
      interactions, enzymatic activities, and structure-function relationships have
      been determined. Screening and characterization of antibodies have been conducted
      using microarrays. Binding of whole cells to the arrays has been exploited to
      search for novel binding proteins and to detect bacteria in blood. Here, we
      review the different techniques for carbohydrate microarray production and
      application. To illustrate the utility of arrays for glycomics research, some
      select experiments are discussed in greater detail.

PMID- 17233560
TI  - Epitomics: global profiling of immune response to disease using protein
      microarrays.
AB  - The immune system retains memory of current and past infections and can sense the
      presence of cancer by elaborating autoantibodies to tumor proteins. In the
      presence of an autoimmune disease, the immune system is an efficient, natural
      biosensor. Therefore we exploit the immune system through a high-throughput
      process to isolate disease-specific epitopes for diagnostic and therapeutic
      purposes. These cloned disease-specific antigens are robotically spotted onto
      protein microarrays and interrogated with serum from the subjects under analyses.
      These arrays deliver personalized profiles of antigenic exposures and therapeutic
      targets for personalized immunotherapy. The immune system is the ultimate
      biosensor, superior to anything a human could create and ready to be exploited
      for biotechnology and biomedicine.

PMID- 17233561
TI  - Clustering methods for microarray gene expression data.
AB  - Within the field of genomics, microarray technologies have become a powerful
      technique for simultaneously monitoring the expression patterns of thousands of
      genes under different sets of conditions. A main task now is to propose
      analytical methods to identify groups of genes that manifest similar expression
      patterns and are activated by similar conditions. The corresponding analysis
      problem is to cluster multi-condition gene expression data. The purpose of this
      paper is to present a general view of clustering techniques used in microarray
      gene expression data analysis.

PMID- 17233562
TI  - Comparison of Amersham and Agilent microarray technologies through quantitative
      noise analysis.
AB  - We carried out a series of replicate experiments on DNA microarrays using two
      cell lines and two technologies--the Agilent Human 1A Microarray and the GE
      Amersham Codelink Uniset Human 20K I Bioarray. We demonstrated that quantifying
      the noise level as a function of signal strength allows identification of the
      absolute and differential mRNA expression levels at which biological variability
      can be resolved above measurement noise. This represents a new formulation of a
      sensitivity threshold that can be used to compare platforms. It was found that
      the correlation in expression level between platforms is considerably worse than
      the correlation between replicate measurements taken using the same platform. In
      addition, we carried out replicate measurements at different stages of sample
      processing. This novel approach enables us to quantify the noise introduced into
      the measurements at each step of the experimental protocol. We demonstrated how
      this information can be used to determine the most efficient means of using
      replicates to reduce experimental uncertainty.

PMID- 17233563
TI  - Integrating large-scale genotype and phenotype data.
AB  - With the completion of the Human Genome Project, a new emphasis is focusing on
      the sequence variation and the resulting phenotype. The number of data available
      from genomic studies addressing this relationship is rapidly growing. In order to
      analyze these data as a whole, they need to be integrated, aggregated and
      annotated in a timely manner. The Pharmacogenetics and Pharmacogenomics Knowledge
      Base PharmGKB; (<www.pharmgkb.org>) assembles and disseminates these data and
      their associated metadata that are needed for unambiguous identification and
      replication. Assembling these data in a timely manner is challenging, and the
      scalability of these data produce major challenges for a knowledge base such as
      PharmGKB. However, it is only through rapid global meta-annotation of these data
      that we will understand the relationship between specific genotype(s) and the
      related phenotype. PharmGKB has confronted these challenges, and these
      experiences and solutions can benefit all genome communities.

PMID- 17233564
TI  - A comparison of statistical tests for detecting differential expression using
      Affymetrix oligonucleotide microarrays.
AB  - Signal quantification and detection of differential expression are critical steps
      in the analysis of Affymetrix microarray data. Many methods have been proposed in
      the literature for each of these steps. The goal of this paper is to evaluate
      several signal quantification methods (GCRMA, RSVD, VSN, MAS5, and Resolver) and
      statistical methods for differential expression (t test, Cyber-T, SAM, LPE,
      RankProducts, Resolver RatioBuild). Our particular focus is on the ability to
      detect differential expression via statistical tests. We have used two different
      datasets for our evaluation. First, we have used the HG-U133 Latin Square spike
      in dataset developed by Affymetrix. Second, we have used data from an in-house
      rat liver transcriptomics study following 30 different drug treatments generated
      using the Affymetrix RAE230A chip. Our overall recommendation based on this study
      is to use GCRMA for signal quantification. For detection of differential
      expression, GCRMA coupled with Cyber-T or SAM is the best approach, as measured
      by area under the receiver operating characteristic (ROC) curve. The integrated
      pipeline in Resolver RatioBuild combining signal quantification and detection of
      differential expression is an equally good alternative for detecting
      differentially expressed genes. For most of the differential expression
      algorithms we considered, the performance using MAS5 signal quantification was
      inferior to that of the other methods we evaluated.

PMID- 17233565
TI  - An opinion too far--the campaign against the Surviving Sepsis Campaign.

PMID- 17233566
TI  - Sp1 elements regulate transcriptional activity within the murine Toll-like
      receptor 4 promoter.
AB  - BACKGROUND AND PURPOSE: Toll-like receptor 4 (TLR4) mediates the innate immune
      response to lipopolysaccharide (LPS) by a complex intracellular signaling pathway
      that activates the transcription factor nuclear factor (NF)-kappaB, with
      subsequent production of inflammatory cytokines. The precise mechanisms involved
      have not been delineated. We hypothesized that specific regulatory elements exist
      within the TLR4 promoter. METHODS: We cloned regions of the murine TLR4 promoter
      (0.25 kb to 2 kb; -2000 bp to +244 bp) into the pGL3-Basic plasmid containing the
      firefly luciferase gene and used the resulting constructs to transfect HEK293 or
      RAW 264.7 cells. After 24 h, we used LPS to stimulate RAW 264.7 cells. We
      quantified relative light units (RLUs) of cell lysates and secreted tumor
      necrosis factor (TNF)-alpha. For pairwise comparison, we used Student's t-test.
      Sequence analysis of the promoter revealed several putative Sp1 sites. We used
      two constructs showing increased promoter activity, TLR4-750/-1 and TLR4-500/-1,
      to transfect cells in the presence of a specific Sp1 inhibitor, mithramycin A.
      RESULTS: Of the six promoter constructs, four showed greater transcriptional
      activity (p < 0.05 vs. pGL3-Basic), as measured by luciferase activity. However,
      we did not observe differences in transcriptional activity of the promoter in
      five of those six constructs when we stimulated transfected RAW 264.7 cells with
      10 ng of LPS. This finding suggests that transcriptional regulation of the
      promoter is unaffected by cellular changes caused by LPS. Both TLR4-750/-1 and
      TLR4-500/-1 showed dose-dependent reductions in transcriptional activity in the
      presence of increasing concentrations of the specific Sp1 inhibitor mithramycin A
      in both HEK293 and RAW 264.7 cells (p < 0.05 vs. no mithramycin A). CONCLUSION:
      At least one Sp1 transcriptional regulatory element is present within the murine
      TLR4 promoter (range -750 bp to -250 bp). This finding holds promise for
      manipulating this fundamental inflammatory response.

PMID- 17233567
TI  - Induction of nitric oxide synthase is a key determinant of progression to
      pulmonary injury in experimental pancreatitis.
AB  - BACKGROUND: The immunomodulatory potential of nitric oxide provides prospective
      strategies to attenuate inappropriate inflammatory reactions. This study tested
      the hypothesis that inhibition of nitric oxide synthase (NOS) reduces end-organ
      injury in pancreatitis. METHODS: Pancreatitis was induced in male Sprague-Dawley
      rats by intraperitoneal (i.p.) injection of 20% L-arginine (500 mg/100 g of body
      weight). Animals were randomized into four groups of 45: Pancreatitis without
      intervention; pre-treatment with i.p. aminoguanidine (AMG) (50 mg/kg), an isoform
      specific inhibitor of inducible NOS; post-treatment with AMG (50 mg/kg); and
      controls. Pancreatic and pulmonary pathology, neutrophil infiltration
      (myeloperoxidase activity), endothelial permeability (bronchoalveolar lavage,
      wet:dry weight ratio), NOS expression, and concentrations of pro-inflammatory
      cytokines (tumor necrosis factor-alpha; interleukin-6) were assessed. RESULTS:
      Inhibition of iNOS significantly reduced end-organ injury. Pancreatic and
      pulmonary injury scores were markedly attenuated in the AMG treatment groups
      compared with no intervention (p < 0.05). Increased endothelial permeability
      (2,411.1 +/- 47.9) and neutrophil sequestration (1.99 +/- 0.01) were manifest in
      the untreated animals compared with AMG pretreatment (1,286.8 +/- 35.1 and
      1,548.0 +/- 0.1; p < 0.05). In addition, a significant reduction in inflammatory
      cytokine concentrations was observed (p < 0.05). CONCLUSIONS: Inhibition of
      inducible NOS encourages a more benign immunologic profile, minimizing the
      deleterious effects of unrestrained neutrophil sequestration subsequent to
      pancreatitis.

PMID- 17233568
TI  - Kinetic therapy beds are associated with more complications in patients with
      thoracolumbar spinal column injuries.
AB  - BACKGROUND AND PURPOSE: Traumatic spine injuries are an important cause of
      morbidity and mortality. Kinetic therapy (KT) beds were designed to minimize skin
      breakdown and enhance clearance of pulmonary secretions by rotating the patient
      from side to side. However, little evidence exists to suggest that fewer
      complications occur in patients with thoracolumbar spine injuries (TLSIs) treated
      preoperatively with a KT bed. We investigated the effect of KT bed use on
      infectious complications and respiratory failure in patients requiring surgery
      for TLSIs. METHODS: We queried the trauma registry of a Level 1 trauma center for
      patients who had surgery for a TLSI from January 1, 1994, through June 30, 2001,
      and performed a retrospective medical record review. Patients were divided into
      two groups according to whether they were treated with a KT bed preoperatively.
      Patient data included age, injury severity score (ISS), admission Glasgow Coma
      Scale score (GCS), time to surgery, narcotics administered in total and during
      the first 24 h after injury, the lowest recorded systolic blood pressure, and
      acute resuscitation volume requirement. Outcome data included infectious
      complications, neurologic deficits, respiratory failure, hospital length of stay
      (LOS), and number of days of ventilator support. Infectious complications
      included pneumonia, urinary tract infections, and surgical site infections.
      RESULTS: Patients treated with a KT bed and patients treated with a conventional
      bed were similar in age, ISS, admission GCS, time to surgery, total narcotics
      administered, lowest recorded systolic blood pressure, and resuscitation
      requirement during the first 24 h. However, patients with neurologic deficits
      were more frequently treated with a KT bed. Infectious complications were more
      common in patients receiving KT bed therapy than among those on conventional
      beds. The incidence of respiratory failure, the number of days of ventilator
      support, and hospital LOS also were significantly higher in patients treated with
      KT beds. The variables most predictive of infectious complications were the
      number of days of ventilator support, the amount of fluid administered during the
      first 24 h, and KT bed therapy (r2 = 0.459). CONCLUSIONS: Patients with TLSIs
      treated with a KT bed had a higher incidence of infectious complications and
      respiratory failure and more days of ventilator support than patients treated
      with a conventional bed despite similar ISS and time to surgical repair. The
      longer hospital LOS in patients treated with a KT bed may be secondary to the
      higher incidence of infectious complications and respiratory failure and the
      greater number of days of ventilator support.

PMID- 17233569
TI  - Risk factors for and effect of a one-year surveillance program on surgical site
      infection at a university hospital in Turkey.
AB  - BACKGROUND: Surveillance of surgical site infection (SSI) is one of the most
      effective methods for decreasing the incidence. We determined the risk factors
      for SSI and the effect of a one-year surveillance program on the rate at a
      tertiary-care center. METHODS: The annual SSI rate before the study period was
      determined in a preliminary study. Risk factors related to SSI, the bacteria
      cultured from infected sites, and the effect of surveillance were then analyzed
      prospectively. Risk factors were determined by logistic regression analysis, and
      95% confidence intervals were calculated. RESULTS: The incidence of SSI decreased
      from 12.8% before the study to 8.8% at the end of the surveillance period. There
      were 90 SSIs (8.8%) in 1,017 procedures during the study period, most of which
      (77; 69%) were detected during the hospital stay. The distribution of superficial
      incisional, deep incisional, and organ/space SSI was 61.1%, 33.4%, and 5.5%,
      respectively. Prolonged preoperative hospital stay (>8 days), abdominal incision,
      early preoperative hair removal, inappropriate antimicrobial prophylaxis, whole
      blood transfusion, famotidine treatment, repair with mesh, age >75 years, wound
      contamination, high American Society of Anesthesiologists score, malnutrition,
      diabetes mellitus, emergency surgery, obesity, and coexistent infection proved to
      be independent risk factors for SSI, whereas the skin closure technique, patient
      sex, presence of malignancy, smoking history, and duration of operation were not.
      Staphylococcus aureus and Escherichia coli were the bacteria isolated most
      frequently. Six infected patients (5.4%) died, four because of SSI. Development
      of SSI increased hospital expenses by around 600 US dollars per patient.
      CONCLUSION: Surveillance even for one year decreases the incidence of SSI.

PMID- 17233570
TI  - Active hexose correlated compound (AHCC) enhances resistance to infection in a
      mouse model of surgical wound infection.
AB  - BACKGROUND: Infection is the most common postoperative complication within the
      surgical wound and during severe trauma. In spite of the use of modern sterile
      techniques and prophylaxis, infection continues to be a leading cause of death in
      these patients. Therefore, it has become crucial to develop new alternatives to
      prevent the effects of trauma and other complications on the immune system and
      improve resistance to infection. The objective of this study was to test the
      prophylactic effects of oral administration of active hexose correlated compound
      (AHCC), a natural immunoenhancer, on survival in a mouse model of surgical soft
      tissue infection. METHODS: The model involves the intramuscular administration of
      a 50% lethal dose (LD50) of K. pneumoniae to mice that have restricted food
      intake for 24 hours prior to and six hours after infection and simulates local
      infection and food deprivation that often occur during trauma or surgical
      procedures. In the present study, AHCC was administrated orally to Swiss Webster
      mice for eight days prior to and during the infection period. Survival, time of
      death, LD50, and clearance of bacteria of this group were compared with those
      control mice receiving the excipient alone. RESULTS: Survival and mean time to
      death were increased significantly in the AHCC-treated group; the LD50 was
      greater in mice receiving AHCC than in mice receiving the excipient. Mice
      receiving AHCC were better able to clear bacteria from their systems than were
      control animals. CONCLUSIONS: The results suggest that AHCC protects mice in this
      model by restoring the immune and other systems negatively affected by trauma,
      infection, and food deprivation. More studies are necessary to determine the
      intrinsic mechanisms involved in this model and whether AHCC can prevent
      infection or improve survival in human beings with severe trauma or undergoing
      surgical procedures.

PMID- 17233571
TI  - In vitro susceptibilities of Escherichia coli isolated from patients with intra
      abdominal infections worldwide in 2002-2004: results from SMART (Study for
      Monitoring Antimicrobial Resistance Trends).
AB  - BACKGROUND: Since 2002, the worldwide Study for Monitoring Antimicrobial
      Resistance Trends (SMART) has tracked resistance patterns among aerobic and
      facultative gram-negative bacilli isolated from patients with intra-abdominal
      infections. Escherichia coli has been by far the most frequently isolated
      species. METHODS: Antimicrobial susceptibilities for consecutive non-duplicate
      isolates of aerobic and facultative gram-negative bacilli recovered from intra
      abdominal infections were determined by standard broth microdilution techniques.
      A subanalysis was performed for E. coli isolates from the first three years of
      the study. RESULTS: A total of 7,002 E. coli isolates were recovered, most
      commonly from the peritoneal cavity followed by the biliary tract. Susceptibility
      rates to the 12 antimicrobial agents tested differed among geographic regions,
      with isolates from Asia/Pacific generally having the highest resistance rates.
      Overall, extended-spectrum beta-lactamase (ESBL)-producers had a more antibiotic
      resistant profile than non-ESBL-producers but usually were susceptible to the
      carbapenems and amikacin. Community-acquired E. coli strains comprised slightly
      more than one-half of the isolates and were susceptible to the agents tested more
      frequently than were hospital-acquired E. coli. CONCLUSIONS: The prevalence of
      antimicrobial resistance among E. coli isolated from intraabdominal infections is
      not inconsequential, especially in the Asia/Pacific region. The carbapenems and
      amikacin were consistently active in vitro against E. coli isolates worldwide,
      including ESBL-producers.

PMID- 17233572
TI  - Streptococcal septic shock after inguinal lymphadenectomy.
AB  - BACKGROUND: Group B Streptococcus is an uncommon cause of sepsis in the non
      pregnant adult. METHODS: Case report and review of the pertinent English-language
      literature. RESULTS: A woman who developed confusion and slurred speech five days
      after aspiration of a postoperative wound seroma is presented. The patient had
      hypotension and fever and required emergency drainage of an infected seroma of
      the groin. Wound culture identified Streptococcus agalactiae as the infecting
      agent. CONCLUSION: Life-threatening sepsis caused by group B streptococci in
      adults is rare, but the organism must be considered as a potential pathogen in
      fulminating surgical site infection.

PMID- 17233573
TI  - Delayed recurrence of postoperative intra-abdominal abscess: an unusual case and
      review of the literature.
AB  - BACKGROUND: Although intra-abdominal abscess is one of the major complications of
      abdominal surgery, the literature documents only a few cases of recurrence after
      a long asymptomatic period. METHODS: Case report and literature review. RESULTS:
      A 66-year-old woman developed a primary subphrenic abscess secondary to
      anastomotic leakage after total gastrectomy. Percutaneous drainage succeeded in
      evacuating the abscess cavity, and broad-spectrum antibiotics apparently
      eradicated the infection. However, a recurrent subphrenic abscess appeared eight
      years later with no intervening signs or symptoms. CONCLUSIONS: The unexpected
      outcome in this case may call into question the appropriate follow-up period
      after treatment for subphrenic abscess. Our experience indicates that clinicians
      should be aware of the possibility of rare delayed recurrence of intra-abdominal
      abscess.

PMID- 17233574
TI  - Culture-negative surgical site infections.
AB  - BACKGROUND: The appearance of postoperative surgical site infection (SSI) in the
      absence of culturable bacterial pathogens is a common dilemma for the surgeon.
      METHODS: The literature was searched through references to primary articles, as
      well as a MEDLINE review, for reports of culture-negative SSIs. RESULTS:
      Potential causes of culture-negative SSIs include prior antimicrobial therapy;
      the presence of fastidious or slow-growing microorganisms such as mycobacteria,
      Mycoplasma spp., and Legionella spp.; infection caused by mundane bacteria that
      may be dismissed as "contaminants"; factitious infection; and others.
      CONCLUSIONS: We review the recognized causes of "culture negative" SSIs and
      discuss the laboratory capabilities that may enhance recognition of many of these
      pathogens and management options.

PMID- 17233575
TI  - Inositol trisphosphate and calcium oscillations.
AB  - InsP3 has two important functions in generating Ca2+ oscillations. It releases
      Ca2+ from the internal store and it can contribute to Ca2+ entry. A hypothesis
      has been developed to describe a mechanism for Ca2+ oscillations with particular
      emphasis on the way agonist concentration regulates oscillator frequency. The
      main idea is that the InsP3 receptors are sensitized to release Ca2+ periodically
      by cyclical fluctuations of Ca2+ within the lumen of the endoplasmic reticulum.
      Each time a pulse of Ca2+ is released, the luminal level of Ca2+ declines and has
      to be replenished before the InsP3 receptors are resensitized to deliver the next
      pulse of Ca2+. It is this loading of the internal store that explains why
      frequency is sensitive to external Ca2+ and may also account for how variations
      in agonist concentration are translated into changes in oscillation frequency.
      Variations in agonist-induced entry of external Ca2+, which can occur through
      different mechanisms, determine the variable rates of store loading responsible
      for adjusting the sensitivity of the InsP3 receptors to produce the periodic
      pulses of Ca2+. The Ca2+ oscillator is an effective analogue-to-digital converter
      in that variations in the concentration of the external stimulus are translated
      into a change in oscillator frequency.

PMID- 17233576
TI  - The IP3 receptor/Ca2+ channel and its cellular function.
AB  - The IP3R [IP3 (inositol 1,4,5-trisphosphate) receptor] is responsible for Ca2+
      release from the ER (endoplasmic reticulum). We have been working extensively on
      the P400 protein, which is deficient in Purkinje-neuron-degenerating mutant mice.
      We have discovered that P400 is an IP3R and we have determined the primary
      sequence. Purified IP3R, when incorporated into a lipid bilayer, works as a Ca2+
      release channel and overexpression of IP3R shows enhanced IP3 binding and channel
      activity. Addition of an antibody blocks Ca2+ oscillations indicating that IP3R1
      works as a Ca2+ oscillator. Studies on the role of IP3R during development show
      that IP3R is involved in fertilization and is essential for determination of
      dorso-ventral axis formation. We found that IP3R is involved in neuronal
      plasticity. A double homozygous mutant of IP3R2 (IP3R type 2) and IP3R3 (IP3R
      type 3) shows a deficit of saliva secretion and gastric juice secretion
      suggesting that IP3Rs are essential for exocrine secretion. IP3R has various
      unique properties: cryo-EM (electron microscopy) studies show that IP3R contains
      multiple cavities; IP3R allosterically and dynamically changes its form
      reversibly (square form-windmill form); IP3R is functional even though it is
      fragmented by proteases into several pieces; the ER forms a meshwork but also
      forms vesicular ER and moves along microtubules using a kinesin motor; X ray
      analysis of the crystal structure of the IP3 binding core consists of an N
      terminal beta-trefoil domain and a C-terminal alpha-helical domain. We have
      discovered ERp44 as a redox sensor in the ER which binds to the luminal part of
      IP3R1 and regulates its activity. We have also found the role of IP3 is not only
      to release Ca2+ but also to release IRBIT which binds to the IP3 binding core of
      IP3R.

PMID- 17233577
TI  - PLCzeta, a sperm-specific PLC and its potential role in fertilization.
AB  - A dramatic rise in intracellular calcium plays a vital role at the moment of
      fertilization, eliciting the resumption of meiosis and the initiation of embryo
      development. In mammals, the rise takes the form of oscillations in calcium
      concentration within the egg, driven by an elevation in inositol trisphosphate.
      The causative agent of these oscillations is proposed to be a recently described
      phosphoinositide-specific phospholipase C, PLCzeta, a soluble sperm protein that
      is delivered into the egg following membrane fusion. In the present review, we
      examine some of the distinctive structural and functional characteristics of this
      crucial enzyme that sets it apart from the other known forms of mammalian PLC.

PMID- 17233578
TI  - Inositol lipids and TRPC channel activation.
AB  - The original hypothesis put forth by Bob Michell in his seminal 1975 review held
      that inositol lipid breakdown was involved in the activation of plasma membrane
      calcium channels or 'gates'. Subsequently, it was demonstrated that while the
      interposition of inositol lipid breakdown upstream of calcium signalling was
      correct, it was predominantly the release of Ca2+ that was activated, through the
      formation of Ins(1,4,5)P3. Ca2+ entry across the plasma membrane involved a
      secondary mechanism signalled in an unknown manner by depletion of intracellular
      Ca2+ stores. In recent years, however, additional non-store-operated mechanisms
      for Ca2+ entry have emerged. In many instances, these pathways involve homologues
      of the Drosophila trp (transient receptor potential) gene. In mammalian systems
      there are seven members of the TRP superfamily, designated TRPC1-TRPC7, which
      appear to be reasonably close structural and functional homologues of Drosophila
      TRP. Although these channels can sometimes function as store-operated channels,
      in the majority of instances they function as channels more directly linked to
      phospholipase C activity. Three members of this family, TRPC3, 6 and 7, are
      activated by the phosphoinositide breakdown product, diacylglycerol. Two others,
      TRPC4 and 5, are also activated as a consequence of phospholipase C activity,
      although the precise substrate or product molecules involved are still unclear.
      Thus the TRPCs represent a family of ion channels that are directly activated by
      inositol lipid breakdown, confirming Bob Michell's original prediction 30 years
      ago.

PMID- 17233579
TI  - Structural studies of phosphoinositide 3-kinase-dependent traffic to
      multivesicular bodies.
AB  - Three large protein complexes known as ESCRT I, ESCRT II and ESCRT III drive the
      progression of ubiquitinated membrane cargo from early endosomes to lysosomes.
      Several steps in this process critically depend on PtdIns3P, the product of the
      class III phosphoinositide 3-kinase. Our work has provided insights into the
      architecture, membrane recruitment and functional interactions of the ESCRT
      machinery. The fan-shaped ESCRT I core and the trilobal ESCRT II core are
      essential to forming stable, rigid scaffolds that support additional, flexibly
      linked domains, which serve as gripping tools for recognizing elements of the MVB
      (multivesicular body) pathway: cargo protein, membranes and other MVB proteins.
      With these additional (non-core) domains, ESCRT I grasps monoubiquitinated
      membrane proteins and the Vps36 subunit of the downstream ESCRT II complex. The
      GLUE (GRAM-like, ubiquitin-binding on Eap45) domain extending beyond the core of
      the ESCRT II complex recognizes PtdIns3P-containing membranes, monoubiquitinated
      cargo and ESCRT I. The structure of this GLUE domain demonstrates that it has a
      split PH (pleckstrin homology) domain fold, with a non-typical phosphoinositide
      binding pocket. Mutations in the lipid-binding pocket of the ESCRT II GLUE domain
      cause a strong defect in vacuolar protein sorting in yeast.

PMID- 17233580
TI  - The role of PI3Ks in the regulation of the neutrophil NADPH oxidase.
AB  - The NADPH oxidase complex of neutrophils and macrophages is an important weapon
      used by these cells to kill microbial pathogens. The regulation of this enzyme
      complex is necessarily complicated by the diverse receptor types that are needed
      to trigger its activation and also the tight control that is required to deliver
      this activation at the appropriate time and place. As such, several signalling
      pathways have been established to regulate the NADPH oxidase downstream of cell
      surface receptors. Central amongst these are PI3K- (phosphoinositide 3-kinase)
      dependent pathways, blockade of which severely limits activation of the oxidase
      to several soluble and particulate stimuli. The precise roles of the
      phosphoinositide products of PI3K activity in regulating NADPH oxidase assembly
      and activation are still unclear, but there is emerging evidence that they play a
      key role via regulation of guanine nucleotide exchange on Rac, a key component in
      the oxidase complex. There is also very strong evidence that the PI3K products
      PtdIns(3,4)P2 and PtdIns3P can bind directly to the PX (Phox homology) domains of
      the core oxidase components p47phox and p40phox respectively. However, the
      significance of these interactions in terms of membrane localization or
      allosteric consequences for the oxidase complex remains to be established.

PMID- 17233581
TI  - Substrate specificity and acute regulation of the tumour suppressor phosphatase,
      PTEN.
AB  - PTEN (phosphatase and tensin homologue deleted on chromosome 10) is a tumour
      suppressor that functions as a PtdIns(3,4,5)P3 3-phosphatase to inhibit cell
      proliferation, survival and growth by antagonizing PI3K (phosphoinositide 3
      kinase)-dependent signalling. Recent work has begun to focus attention on
      potential biological functions of the protein phosphatase activity of PTEN and on
      the possibility that some of its functions are phosphatase-independent. We
      discuss here the structural and regulatory mechanisms that account for the
      remarkable specificity of PTEN with respect to its PtdIns substrates and how it
      avoids the soluble headgroups of PtdIns that occur commonly in cells. Secondly we
      discuss the concept of PTEN as a constitutively active enzyme that is subject to
      negative regulation both physiologically and pathologically. Thirdly, we review
      the evidence that PTEN functions as a dual specificity phosphatase with discrete
      lipid and protein substrates. Lastly we present a current model of how PTEN may
      participate in the control of cell migration.

PMID- 17233582
TI  - Pleckstrin homology (PH) domains and phosphoinositides.
AB  - PH (pleckstrin homology) domains represent the 11th most common domain in the
      human proteome. They are best known for their ability to bind phosphoinositides
      with high affinity and specificity, although it is now clear that less than 10%
      of all PH domains share this property. Cases in which PH domains bind specific
      phosphoinositides with high affinity are restricted to those phosphoinositides
      that have a pair of adjacent phosphates in their inositol headgroup. Those that
      do not [PtdIns3P, PtdIns5P and PtdIns(3,5)P2] are instead recognized by distinct
      classes of domains including FYVE domains, PX (phox homology) domains, PHD (plant
      homeodomain) fingers and the recently identified PROPPINs (b-propellers that bind
      polyphosphoinositides). Of the 90% of PH domains that do not bind strongly and
      specifically to phosphoinositides, few are well understood. One group of PH
      domains appears to bind both phosphoinositides (with little specificity) and Arf
      (ADP-ribosylation factor) family small G-proteins, and are targeted to the Golgi
      apparatus where both phosphoinositides and the relevant Arfs are both present.
      Here, the PH domains may function as coincidence detectors. A central challenge
      in understanding the majority of PH domains is to establish whether the very low
      affinity phosphoinositide binding reported in many cases has any functional
      relevance. For PH domains from dynamin and from Dbl family proteins, this weak
      binding does appear to be functionally important, although its precise
      mechanistic role is unclear. In many other cases, it is quite likely that
      alternative binding partners are more relevant, and that the observed PH domain
      homology represents conservation of structural fold rather than function.

PMID- 17233583
TI  - Evolutionarily conserved structural and functional roles of the FYVE domain.
AB  - The FYVE domain is an approx. 80 amino acid motif that binds to the
      phosphoinositide PtdIns3P with high specificity and affinity. It is present in 38
      predicted gene products within the human genome, but only in 12-13 in
      Caenorhabditis elegans and Drosophila melanogaster. Eight of these are highly
      conserved in all three organisms, and they include proteins that have not been
      characterized in any species. One of these, WDFY2, appears to play an important
      role in early endocytosis and was revealed in a RNAi (RNA interference) screen in
      C. elegans. Interestingly, some proteins contain FYVE-like domains in C. elegans
      and D. melanogaster, but have lost this domain during evolution. One of these is
      the homologue of Rabatin-5, a protein that, in mammalian cells, binds both Rab5
      and Rabex-5, a guanine-nucleotide exchange factor for Rab5. Thus the Rabatin-5
      homologue suggests that mechanisms to link PtdIns3P and Rab5 activation developed
      in evolution. In mammalian cells, these mechanisms are apparent in the existence
      of proteins that bind PtdIns3P and Rab GTPases, such as EEA1, Rabenosyn-5 and
      Rabip4'. Despite the comparable ability to bind to PtdIns3P in vitro, FYVE
      domains display widely variable abilities to interact with endosomes in intact
      cells. This variation is due to three distinct properties of FYVE domains
      conferred by residues that are not involved in PtdIns3P head group recognition:
      These properties are: (i) the propensity to oligomerize, (ii) the ability to
      insert into the membrane bilayer, and (iii) differing electrostatic interactions
      with the bilayer surface. The different binding properties are likely to regulate
      the extent and duration of the interaction of specific FYVE domain-containing
      proteins with early endosomes, and thereby their biological function.

PMID- 17233584
TI  - The role of the phosphoinositides at the Golgi complex.
AB  - Eukaryotic cells are organized into a complex system of subcompartments, each
      with its distinct protein and lipid composition. A continuous flux of membranes
      crosses these compartments, and in some cases direct connections exist between
      the different organelles. It is thus surprising that they can maintain their
      individual identities. Small GTPases and the phosphoinositides have emerged as
      the key regulators in the maintenance of the identity of the Golgi complex. This
      property is due to their ability to act either alone or, more often, in
      combination, as cues directing and controlling the recruitment of proteins that
      possess phosphoinositide-binding domains. Among these many proteins there are the
      lipid transfer proteins, which can transfer ceramide, oxysterol, cholesterol and
      possibly glucosylceramide. By regulating these lipid transfer proteins in this
      way, this binomial combination of the small GTPases and the phosphoinositides
      acquires a further important role: control of the synthesis and/or distribution
      of other important integral constituents of cell organelles, such as the
      sphingolipids and cholesterol. This role is particularly relevant at the level of
      the Golgi complex, a key organelle in the biosynthesis, transport and sorting of
      both lipids and proteins that is located at the intersection of the secretory and
      endocytic pathways.

PMID- 17233585
TI  - PtdIns5P: a little phosphoinositide with big functions?
AB  - Phosphoinositides are minor constituents of cell membranes playing a critical
      role in the regulation of many cellular functions. Recent discoveries indicate
      that mutations in several phosphoinositide kinases and phosphatases generate
      imbalances in the levels of phosphoinositides, thereby leading to the development
      of human diseases. Although the roles of phosphoinositide 3-kinase products and
      PtdIns(4,5)P2 were largely studied these last years, the potential role of
      phosphatidylinositol monophosphates as direct signalling molecules is just
      emerging. PtdIns5P, the least characterized phosphoinositide, appears to be a new
      player in cell regulation. This review will summarize the current knowledge on
      the mechanisms of synthesis and degradation of PtdIns5P as well as its potential
      roles.

PMID- 17233586
TI  - Our FABulous VACation: a decade of phosphatidylinositol 3,5-bisphosphate.
AB  - PtdIns(3,5)P2 was discovered about a decade ago and much of the machinery that
      makes, degrades and senses it has been uncovered. Despite this, we still lack a
      complete understanding of how the pieces fit together but some patterns are
      beginning to emerge. Molecular functions for PtdIns(3,5)P2 are also elusive, but
      the identification of effectors offers a way into some of these processes. An
      examination of the defects associated with loss of synthesis of PtdIns(3,5)P2 in
      lower and higher eukaryotes begins to suggest a unifying theme; this lipid
      regulates membrane retrieval via retrograde trafficking from distal compartments
      to organelles that are more proximal in the endocytic/lysosomal system. Another
      unifying theme is stress signalling to organelles, possibly both to change their
      morphology in response to external insults and to maintain the lumenal pH or
      membrane potential of organelles. The next few years seem likely to uncover
      details of the molecular mechanisms underlying the biology of this fascinating
      lipid. This review also highlights some areas where further research is needed.

PMID- 17233587
TI  - Phosphoinositides in phagolysosome and autophagosome biogenesis.
AB  - Interconversions of phosphoinositides play a pivotal role during phagocytosis and
      at the subsequent stages of phagosomal maturation into the phagolysosome. Several
      model systems have been used to study the role of phosphoinositides in phagosomal
      membrane remodelling. These include phagosomes formed by inanimate objects such
      as latex beads, or pathogenic bacteria, e.g. Mycobacterium tuberculosis. The
      latter category provides naturally occurring tools to dissect membrane
      trafficking processes governing phagolysosome biogenesis. M. tuberculosis
      persists in infected macrophages by blocking Rab conversion and affecting Rab
      effectors. One of the major Rab effectors involved in this process is the type
      III phosphatidylinositol 3-kinase hVPS34. The lipid kinase hVPS34 and its
      enzymatic product PtdIns3P are critical for the default pathway of phagosomal
      maturation into phagolysosomes. Mycobacteria block PtdIns3P production and thus
      arrest phagosomal maturation. PtdIns3P is also critical for the process of
      autophagy, recently recognized as an effector of innate immunity defenses.
      Induction of autophagy by pharmacological, physiological, or immunological means,
      overcomes mycobacterial phagosome maturation block in a PtdIns3P generation
      dependent manner and eliminates intracellular M. tuberculosis. PtdIns3P and
      PtdIns3P-dependent processes represent an important cellular nexus where
      fundamental trafficking processes, disease causing host-pathogen interactions,
      and innate and adaptive immunity defense mechanisms meet.

PMID- 17233589
TI  - The inositol polyphosphate 5-phosphatases: traffic controllers, waistline
      watchers and tumour suppressors?
AB  - Phosphoinositide signals regulate cell proliferation, differentiation,
      cytoskeletal rearrangement and intracellular trafficking. Hydrolysis of
      PtdIns(4,5)P2 and PtdIns(3,4,5)P3, by inositol polyphosphate 5-phosphatases
      regulates synaptic vesicle recycling (synaptojanin-1), hematopoietic cell
      function [SHIP1(SH2-containing inositol polyphosphate 5-phosphatase-1)], renal
      cell function [OCRL (oculocerebrorenal syndrome of Lowe)] and insulin signalling
      (SHIP2). We present here a detailed review of the characteristics of the ten
      mammalian 5-phosphatases. Knockout mouse phenotypes and underexpression studies
      are associated with significant phenotypic changes, indicating non-redundant
      roles, despite, in many cases, overlapping substrate specificity and tissue
      expression. The extraordinary complexity in the control of phosphoinositide
      signalling continues to be revealed.

PMID- 17233588
TI  - Type II PtdInsP kinases: location, regulation and function.
AB  - The regulation of the synthesis of PtdIns(4,5)P2 is emerging as being as complex
      as we might expect from the multi-functional nature of this lipid. In the present
      chapter we focus on one aspect of inositide metabolism, which is the functions of
      the Type II PIPkins (Type II PtdInsP kinases). These are primarily PtdIns5P 4
      kinases, although in vitro they will also phosphorylate PtdIns3P to
      PtdIns(3,4)P2. Thus they have three, not necessarily exclusive, functions: to
      make PtdIns(4,5)P2 by a quantitatively minor route, to remove PtdIns5P and to
      make PtdIns(3,4)P2 by a route that does not involve a Class I PtdIns 3-kinase.
      None of these three possible functions has yet been unambiguously proven or ruled
      out. Of the three isoforms, alpha and beta are widely expressed, the IIalpha
      being predominantly cytosolic and the IIbeta primarily nuclear. PIPkin IIgamma
      has a much more restricted tissue expression pattern, and appears to be localized
      primarily to intracellular vesicles. Here we introduce in turn each of the three
      Type II PIPkins, and discuss what we know about their localization, their
      regulation and their function.

PMID- 17233590
TI  - Inositol polyphosphate kinases: regulators of nuclear function.
AB  - Recent work has uncovered roles for inositide signalling pathways downstream of
      phospholipase C activation and inositol 1,4,5-trisphosphate in the regulation of
      nuclear processes including gene expression, mRNA export and DNA metabolism. The
      identification of several IPKs (inositol polyphosphate kinases) has renewed
      interest in the cellular roles of inositol tetra-, penta-, hexa- and pyro
      phosphates. Discoveries of inositide receptors and novel mechanisms of inositide
      action have provided important insights into how such messengers couple to
      nuclear machinery. In this chapter, we discuss the IPK family members and the
      nuclear processes that their inositide products regulate.

PMID- 17233591
TI  - Multiple functions of inositolphosphorylceramides in the formation and
      intracellular transport of glycosylphosphatidylinositol-anchored proteins in
      yeast.
AB  - The mature sphingolipids of yeast consist of IPCs (inositolphosphorylceramides)
      and glycosylated derivatives thereof. Beyond being an abundant membrane
      constituent in the organelles of the secretory pathway, IPCs are also used to
      constitute the lipid moiety of the majority of GPI (glycosylphosphatidylinositol)
      proteins, while a minority of GPI proteins contain PI (phosphatidylinositol).
      Thus all GPI anchor lipids (as well as free IPCs) typically contain C26 fatty
      acids. However, the primary GPI lipid that isadded to newly synthesized proteins
      in the endoplasmic reticulum consists of a PI with conventional C16 and C18 fatty
      acids. A new class of enzymes is required to replace the fatty acid in sn-2 by a
      C26 fatty acid. Cells lacking this activity make normal amounts of GPI proteins
      but accumulate GPI anchors containing lyso-PI. As a consequence, the endoplasmic
      reticulum to Golgi transport of the GPI protein Gas1p is slow, and mature Gas1p
      is lost from the plasma membrane into the medium. The GPI anchor containing C26
      in sn-2 can further be remodelled by the exchange of diacylglycerol for ceramide.
      This process is also dependent on the presence of specific phosphorylethanolamine
      side-chains on the GPI anchor.

PMID- 17233592
TI  - Understanding the biological significance of diphosphoinositol polyphosphates
      ('inositol pyrophosphates').
AB  - Among the many derivatives of the inositol-based signalling family are a subgroup
      that possess diphosphates. In this review, some recent research into the actions
      of these specialized polyphosphates is analysed, and key goals for future studies
      are identified, which, it is hoped, will result in the wider cell-signalling
      community giving considerably greater attention to this intriguing but relatively
      neglected class of inositol polyphosphates.

PMID- 17233593
TI  - Evolution of the diverse biological roles of inositols.
AB  - Several of the nine hexahydroxycylohexanes (inositols) have functions in Biology,
      with myo-inositol (Ins) in most of the starring roles; and Ins polyphosphates are
      amongst the most abundant organic phosphate constituents on Earth. Many Archaea
      make Ins and use it as a component of diphytanyl membrane phospholipids and the
      thermoprotective solute di-L-Ins-1,1'-phosphate. Few bacteria make Ins or use it,
      other than as a carbon source. Those that do include hyperthermophilic
      Thermotogales (which also employ di-L-Ins-1,1'-phosphate) and actinomycetes such
      as Mycobacterium spp. (which use mycothiol, an inositol-containing thiol, as an
      intracellular redox reagent and have characteristic phosphatidylinositol-linked
      surface oligosaccharides). Bacteria acquired their Ins3P synthases by lateral
      gene transfer from Archaea. Many eukaryotes, including stressed plants, insects,
      deep-sea animals and kidney tubule cells, adapt to environmental variation by
      making or accumulating diverse inositol derivatives as 'compatible' solutes.
      Eukaryotes use phosphatidylinositol derivatives for numerous roles in cell
      signalling and regulation and in protein anchoring at the cell surface.
      Remarkably, the diradylglycerol cores of archaeal and eukaryote/bacterial
      glycerophospholipids have mirror image configurations: sn-2,3 and sn-1,2
      respectively. Multicellular animals and amoebozoans exhibit the greatest variety
      of functions for PtdIns derivatives, including the use of PtdIns(3,4,5)P3 as a
      signal. Evolutionarily, it seems likely that (i) early archaeons first made myo
      inositol approx. 3500 Ma (million years) ago; (ii) archeons brought inositol
      derivatives into early eukaryotes (approx. 2000 Ma?); (iii) soon thereafter,
      eukaryotes established ubiquitous functions for phosphoinositides in membrane
      trafficking and Ins polyphosphate synthesis; and (iv) since approx. 1000 Ma,
      further waves of functional diversification in amoebozoans and metazoans have
      introduced Ins(1,4,5)P3 receptor Ca2+ channels and the messenger role of
      PtdIns(3,4,5)P3.

PMID- 17233594
TI  - Regulation of phospholipase D activity, membrane targeting and intracellular
      trafficking by phosphoinositides.
AB  - Generation of PA (phosphatidic acid) by PLD (phospholipase D)-catalysed
      hydrolysis of phosphatidylcholine plays a pivotal role in cellular signalling
      pathways that regulate organization of the actin cytoskeleton, vesicular
      transport and exocytosis and stimulation of cell growth and survival. PLD
      regulation and function are intimately linked with phosphoinositide metabolism.
      Phosphatidyl 4-phosphate 5-kinase is stimulated by PA in vitro and this enzyme is
      the downstream effector of a significant subset of PLD signalling pathways. Yeast
      and mammalian PLDs are potently and specifically activated by the product of this
      kinase, PtdIns(4,5)P2, through interactions mediated by a polybasic motif within
      the catalytic core of the enzyme. Integrity of this motif is critical for agonist
      activation of mammalian PLD and for PLD function in secretion, sporulation and
      exocytosis in vivo. Although dispensable for catalysis in vitro, these PLD
      enzymes also contain N-terminal PH (pleckstrin) and PX (phox) homology domains.
      Binding studies using recombinantly expressed PLD fragments indicate that the PH
      and PX domains also interact specifically with distinct phosphoinositide ligands.
      Both the PX and PH domains are important for PLD function by controlling the
      dynamic association of the enzyme with the plasma membrane and its intracellular
      trafficking by the endocytic pathway. These results identify two distinct modes
      of regulation of PLD by phosphoinositides: stimulation of catalysis mediated by
      the polybasic domain and dynamic regulation of membrane targeting mediated
      primarily by the PH and PX domains.

PMID- 17233595
TI  - Trafficking of phosphatidylinositol by phosphatidylinositol transfer proteins.
AB  - PtdIns is synthesized at the endoplasmic reticulum and its intracellular
      distribution to other organelles can be facilitated by lipid transfer proteins
      [PITPs (phosphatidylinositol transfer proteins)]. In this review, I summarize the
      current understanding of how PITPs are regulated by phosphorylation, how can they
      dock to membranes to exchange their lipid cargo and how cells use PITPs in signal
      transduction and membrane delivery. Mammalian PITPs, PITPalpha and PITPbeta, are
      paralogous genes that are 94% similar in sequence. Their structural design
      demonstrates that they can sequester PtdIns or PtdCho (phosphatidylcholine) in
      their hydrophobic cavity. To deliver the lipid cargo to a membrane, PITP has to
      undergo a conformational change at the membrane interface. PITPs have a higher
      affinity for PtdIns than PtdCho, which is explained by hydrogen-bond contacts
      between the inositol ring of PtdIns and the side-chains of four amino acid
      residues, Thr59, Lys61, Glu86 and Asn90, in PITPs. Regardless of species, these
      residues are conserved in all known PITPs. PITP transfer activity is regulated by
      a conserved serine residue (Ser166) that is phosphorylated by protein kinase C.
      Ser166 is only accessible for phosphorylation when a conformational change occurs
      in PITPs while docking at the membrane interface during lipid transfer, thereby
      coupling regulation of activity with lipid transfer function. Biological roles of
      PITPs include their ability to couple phospholipase C signalling to neurite
      outgrowth, cell division and stem cell growth.

PMID- 17233596
TI  - Challenges to macromolecular drug delivery.
AB  - The use of macromolecules, particularly monoclonal antibodies, as therapeutic
      agents has come to the forefront in recent years. The biodistribution and
      delivery issues for protein drugs are shared to a substantial degree with other
      emerging therapeutic approaches including pharmacologically active nucleic acids
      and nanoparticles. A generalized approach to these issues involves consideration
      of the multiple biological barriers that stand between the macromolecular drug or
      nanoparticle at its site of administration and its ultimate biological target.
      Considerations of size, stability, non-specific versus specific associations and
      potency versus toxicity all play a role. The creation of delivery approaches that
      combine high specificity for the target cell or tissue, high therapeutic payload
      and modest toxicity remains a challenge, although some very promising examples
      have emerged recently. A variety of sophisticated targeting strategies, based
      primarily on combinatorial library methods, when used in combination with new
      technologies to identify cell-surface receptor 'signatures' of specific tissues,
      will facilitate advances in targeted delivery of macromolecules and
      nanoparticles. The challenges to contemporary macromolecule drug delivery are
      complex, thus new research paradigms are emerging that combine the talents of
      physical and biological scientists to address this key issue for modern
      pharmacology and therapeutics.

PMID- 17233597
TI  - A non-covalent peptide-based strategy for siRNA delivery.
AB  - The major obstacle to clinical development of siRNAs (short interfering RNAs),
      like for most of the nucleic-acid-based strategies, is their poor cellular uptake
      and bioavailability. Although several viral and non-viral strategies have been
      proposed to improve siRNA delivery, their applications in vivo remain a major
      challenge. We have developed a new strategy, based on a short amphipathic
      peptide, MPG, that is able to form stable nanoparticles with siRNA. MPG-based
      particles enter the cell independently of the endosomal pathway and can
      efficiently deliver siRNA in a fully biologically active form into a variety of
      cell lines and in vivo. This short review will discuss the mechanism and the
      potency of the MPG strategy for siRNA delivery both in vitro and in vivo.

PMID- 17233598
TI  - Challenges in non-viral ocular gene transfer.
AB  - Nowadays, there is no effective treatment for many retinal disorders. Knowledge
      of the genetic basis of many severe ocular diseases may allow for alternative
      treatments by gene therapy. Non-viral gene complexes, such as lipo- and poly
      plexes, can be delivered to the posterior segment, most often the target tissue,
      by intravitreal or subretinal injection. Since subretinal injections are very
      invasive, intravitreal injection is a promising alternative route to deliver gene
      complexes into the eye. However, the drawback of this technique is the relative
      long distance the complexes have to travel through the vitreous gel before they
      reach the retina. This mini-review reports on how non-viral gene complexes behave
      in vitreous. It especially focuses on how the coating of lipoplexes with
      poly(ethylene glycol) influences their behaviour in vitreous and the transfection
      of retinal pigment epithelium.

PMID- 17233599
TI  - Combinatorial selection and delivery of thioaptamers.
AB  - Oligonucleotide-based agents are emerging as potential therapeutic agents that
      can be attractive alternatives for the small-molecule chemical drugs.
      Monothiophosphate-backbone-modified DNA aptamers (thioaptamers) that specifically
      and tightly bind to the RNase H domain of the HIV RT (reverse transcriptase) have
      been isolated from nucleic acid libraries using combinatorial selection methods.
      The selected thioaptamer inhibited RNase H activity of the HIV RT in in vitro
      studies. In cell cultures, the transfected thioaptamer markedly reduced HIV
      production in a dose-dependent manner. Gel electrophoretic mobility-shift assays
      and NMR spectroscopy showed that the selected thioaptamer binds to the isolated
      RNase H domain, but did not bind to a structurally similar RNase H from
      Escherichia coli. In cell cultures, the transfected thioaptamer showed a dose
      dependent inhibition of HIV replication, with a maximal inhibition of 83%. Using
      various liposome-delivery agents, the DNA thioaptamer was transfected into HIV
      infected astrocytoma adherent cells with greater than 70% efficiency.

PMID- 17233600
TI  - Peptide-based delivery of nucleic acids: design, mechanism of uptake and
      applications to splice-correcting oligonucleotides.
AB  - CPPs (cell-penetrating peptides) have given rise to much interest for the
      delivery of biomolecules such as peptides, proteins or ONs (oligonucleotides).
      CPPs and their conjugates were initially thought to translocate through the cell
      membrane by a non-endocytotic mechanism which has recently been re-evaluated.
      Basic-amino-acid-rich CPPs first interact with cell-surface proteoglycans before
      being internalized by endocytosis. Sequestration and degradation in endocytotic
      vesicles severely limits the cytoplasmic and nuclear delivery of the conjugated
      biomolecules. Accordingly, splicing correction by CPP-conjugated steric-block ON
      analogues is inefficient in the absence of endosomolytic agents. New arginine
      rich CPPs allowing efficient splicing correction by conjugated PNAs (peptide
      nucleic acids) or PMO (phosphorodiamidate morpholino oligomer) steric blockers in
      the absence of endosomolytic agents have recently been defined in our group and
      are currently being characterized. They offer promising leads for the development
      of efficient cellular delivery vectors for therapeutic steric-block ON analogues.

PMID- 17233601
TI  - Designing polymer conjugates as lysosomotropic nanomedicines.
AB  - Marriage of cell biology (the concept of 'lysosomotropic drug delivery') and the
      realization that water-soluble synthetic polymers might provide an ideal platform
      for targeted drug delivery led to the first synthetic polymer-drug conjugates
      that entered clinical trials as anticancer agents. Conceptually, polymer
      conjugates share many features with other macromolecular drugs, but they have the
      added advantage of the versatility of synthetic chemistry that allows tailoring
      of molecular mass and addition of biomimetic features. Conjugate characteristics
      must be optimized carefully to ensure that the polymeric carrier is biocompatible
      and that the polymer molecular mass enables tumour-selective targeting followed
      by endocytic internalization. The polymer-drug linker must be stable in transit,
      but be degraded at an optimal rate intracellularly to liberate active drug. Our
      early studies designed two HPMA [N-(2-hydroxypropyl)methacrylamide] copolymer
      conjugates containing doxorubicin that became the first synthetic polymer-drug
      conjugates to be tested in phase I/II clinical trials. Since, a further four HPMA
      copolymer-anticancer drug conjugates (most recently polymer platinates) and the
      first polymer-based gamma-camera imaging agents followed. Polymer-drug linkers
      cleaved by lysosomal thiol-dependent proteases and the reduced pH of endosomes
      and lysosomes have been used widely to facilitate drug liberation. It is becoming
      clear that inappropriate trafficking and/or malfunction of enzymatic activation
      can lead to new mechanisms of clinical resistance. Recent studies have described
      HPMA copolymer conjugates carrying a combination of both endocrine and
      chemotherapy that are markedly more active than individual conjugates carrying a
      single drug. Moreover, current research is investigating novel dendritic polymer
      architectures and novel biodegradable polymers as drug carriers that will provide
      improved drug delivery and imaging probes in the future. The present paper
      reviews the clinical status of polymeric anticancer agents, the rationale for the
      design of polymer therapeutics and discusses the benefits and challenges of
      lysosomotropic delivery.

PMID- 17233603
TI  - Gene delivery by cationic lipids: in and out of an endosome.
AB  - Cationic lipids are exploited as vectors ('lipoplexes') for delivering nucleic
      acids, including genes, into cells for both therapeutic and cell biological
      purposes. However, to meet therapeutic requirements, their efficacy needs major
      improvement, and better defining the mechanism of entry in relation to eventual
      transfection efficiency could be part of such a strategy. Endocytosis is the
      major pathway of entry, but the relative contribution of distinct endocytic
      pathways, including clathrin- and caveolae-mediated endocytosis and/or
      macropinocytosis is as yet poorly defined. Escape of DNA/RNA from endosomal
      compartments is thought to represent a major obstacle. Evidence is accumulating
      that non-lamellar phase changes of the lipoplexes, facilitated by intracellular
      lipids, which allow DNA to dissociate from the vector and destabilize endosomal
      membranes, are instrumental in plasmid translocation into the cytosol, a
      prerequisite for nuclear delivery. To further clarify molecular mechanisms and to
      appreciate and overcome intracellular hurdles in lipoplex-mediated gene delivery,
      quantification of distinct steps in overall transfection and proper model systems
      are required.

PMID- 17233602
TI  - Dendrimers as multi-purpose nanodevices for oncology drug delivery and diagnostic
      imaging.
AB  - Dendrimers are routinely synthesized as tuneable nanostructures that may be
      designed and regulated as a function of their size, shape, surface chemistry and
      interior void space. They are obtained with structural control approaching that
      of traditional biomacromolecules such as DNA/RNA or proteins and are
      distinguished by their precise nanoscale scaffolding and nanocontainer
      properties. As such, these important properties are expected to play an important
      role in the emerging field of nanomedicine. This review will describe progress on
      the use of these features for both targeted diagnostic imaging and drug-delivery
      applications. Recent efforts have focused on the synthesis and pre-clinical
      evaluation of a multipurpose STARBURST PAMAM (polyamidoamine) dendrimer prototype
      that exhibits properties suitable for use as: (i) targeted, diagnostic MRI
      (magnetic resonance imaging)/NIR (near-IR) contrast agents, (ii) and/or for
      controlled delivery of cancer therapies. Special emphasis will be placed on the
      lead candidate, namely [core: 1,4-diaminobutane; G (generation)=4.5], [dendri
      PAMAM(CO(2)Na)(64)]. This dendritic nanostructure (i.e. approximately 5.0 nm
      diameter) was selected on the basis of a very favourable biocompatibility profile
      [The Nanotechnology Characterization Laboratory (NCL), an affiliate of the
      National Cancer Institute (NCI), has completed extensive in vitro studies on the
      lead compound and have found it to be very benign, non-immunogenic and highly
      biocompatible], the expectation that it will exhibit desirable mammalian kidney
      excretion properties and demonstrated targeting features.

PMID- 17233604
TI  - Receptor-mediated internalization of chelator-PNA-peptide hybridization probes
      for radioimaging or magnetic resonance imaging of oncogene mRNAs in tumours.
AB  - Early external detection of cancer gene activity might enable early treatment of
      cancer and might reduce cancer mortality. We hypothesized that oncogene mRNA
      overexpressed at thousands of copies per malignant cell in a zone of transformed
      cells could be imaged externally by scintigraphic imaging, PET (positron emission
      tomography) or MRI (magnetic resonance imaging) with PNA (peptide nucleic acid)
      hybridization probes that include chelators for metal cations and a cyclized
      peptide analogue of IGF-1 (insulin-like growth factor 1), D(Cys-Ser-Lys-Cys), to
      mediate internalization by IGF1R (IGF-1 receptor) overexpressed on cancer cells.
      We observed that human MCF7 breast cancer cells that overexpress IGF1R
      efficiently internalized fluorescein-chelator-PNA-D(Cys-Ser-Lys-Cys) to the
      cytoplasm, but not with D(Cys-Ala-Ala-Cys). Scintigraphic imaging of MCF7
      xenografts in immunocompromised mice revealed that CCND1 and MYC
      [(99m)Tc]chelator-PNA-D(Cys-Ser-Lys-Cys) probes yielded xenograft. PET imaging
      with [(64)Cu]chelator-PNA-D(Cys-Ser-Lys-Cys) yielded stronger signals.
      Scintigraphic imaging of human AsPC1 pancreas cancer xenografts with
      [(99m)Tc]chelator-KRAS PNA-D(Cys-Ser-Lys-Cys) yielded strong xenograft signals.
      Stronger xenograft image intensities were obtained by PET imaging of
      [(64)Cu]chelator-KRAS PNA-D(Cys-Ser-Lys-Cys). MRI required extension of chelator
      polydiamidopropanoate dendrimers from the N-termini of the PNA probes to increase
      the number of contrast paramagnetic gadolinium (III) cations per probe. These
      results provide a basis for detection of oncogene activity in tissues from
      outside the body by hybridization with metal-chelator-PNA-peptides that are
      selectively internalized by cancer cells.

PMID- 17233605
TI  - The TRP channel superfamily: insights into how structure, protein-lipid
      interactions and localization influence function.
AB  - TRP (transient receptor potential) cationic channels are key molecules that are
      involved in a variety of diverse biological processes ranging from fertility to
      osmosensation and nociception. Increasing our knowledge of these channels will
      help us to understand a range of physiological and pathogenic processes, as well
      as highlighting potential therapeutic drug targets. The founding members of the
      TRP family, Drosophila TRP and TRPL (TRP-like) proteins, were identified within
      the last two decades and there has been a subsequent explosion in the number and
      type of TRP channel described. Although information is accumulating as to the
      function of some of the TRP channels, the activation and inactivation mechanisms,
      structure, and interacting proteins of many, if not most, are awaiting
      elucidation. The Cell and Molecular Biology of TRP Channels Meeting held at the
      University of Bath included speakers working on a number of the different
      subfamilies of TRP channels and provided a basis for highlighting both
      similarities and differences between these groups. As the TRP channels mediate
      diverse functions, this meeting also brought together an audience with wide
      ranging research interests, including biochemistry, cell biology, physiology and
      neuroscience, and inspired lively discussion on the issues reviewed herein.

PMID- 17233606
TI  - Molecular determinants of TRP channel assembly.
AB  - Calcium channels play important roles in cellular signalling. TRP (transient
      receptor potential) channels form a superfamily of calcium channels through which
      Ca(2+) enters the cell. TRPs have six transmembrane segments with a putative pore
      between the fifth and the sixth segments, and assemble in tetrameric complexes to
      form functional Ca(2+) channels. They are thus similar to K(V) (voltage-gated
      potassium channel) channels in terms of structure and molecular determinants that
      promote subunit assembly. In this review, the molecular determinants mediating
      the assembly of Drosophila TRP, TRPC (TRP canonical), TRPV (TRP vanilloid) and
      K(V) channels are described.

PMID- 17233607
TI  - Assembly domains in TRP channels.
AB  - The large family of mammalian TRP (transient receptor potential) ion channels
      encompasses diverse sensory functions. TRP proteins consist of six transmembrane
      domains, with a pore-loop motif between the fifth and sixth domains and cytosolic
      N- and C-termini. The intracellular strands not only interact with various
      proteins and lipids, but also include essential multimerization regions. This
      review summarizes the current knowledge of the intrinsic assembly domains that
      assure tetrameric TRP channel formation.

PMID- 17233608
TI  - Subunit interaction in channel assembly and functional regulation of transient
      receptor potential melastatin (TRPM) channels.
AB  - Functional TRPM (transient receptor potential melastatin) ion channels are
      multimers, thought to be tetramers. Subunit interaction is the prerequisite step
      in channel assembly, and the specificity of subunit interaction is crucial in
      assembling channels with distinct functional properties. In addition, expression
      of short non-functional subunits and their interaction with full-length subunits
      serve as one of the post-translational mechanisms regulating the channel
      activity. This paper aims to provide an overview of the current knowledge of TRPM
      subunit interactions and their roles in assembly and functional regulation of the
      TRPM channels.

PMID- 17233609
TI  - TRPM3, a biophysical enigma?
AB  - TRPM3 [TRP (transient receptor potential) melastatin 3] is one of the least
      investigated proteins of the TRP family of ion channels. Heterologously expressed
      TRPM3 channels are constitutively active, have an outwardly rectifying current
      voltage relationship and are inhibited by intracellular Mg(2+) ions. Besides
      these rather common features, in which TRPM3 channels resemble the closely
      related channels TRPM6 and TRPM7, TRPM3 channels have several unique
      characteristics. The TRPM3 gene encodes a plethora of different proteins owing to
      alternative splicing and alternative exon usage. One site of alternative splicing
      affects the ion-conducting pore region and profoundly alters the pore properties
      of the encoded channels. The channels having the longer pore region efficiently
      conduct univalent cations, but are only poorly permeated by bivalent cations.
      Conversely, the channels with the shorter pore region are highly permeable to
      bivalent cations. Unusually, the short-pore TRPM3 channels are inhibited by
      extracellular Na(+) ions. At physiological sodium concentration, this block is
      very strong, making it difficult to envision a physiological function for these
      ion channels. Recently, pharmacological investigations have been initiated in
      order to identify substances that influence TRPM3 channel activity. With the use
      of such substances, it might be possible to identify TRPM3 channels in their
      native environment and to elucidate some of their physiological roles. Hopefully,
      TRPM3 channels will then no longer appear to be as enigmatic as they do right
      now.

PMID- 17233610
TI  - TRP channels activated by extracellular hypo-osmoticity in epithelia.
AB  - TRP (transient receptor potential) channels comprise a superfamily of non
      selective cation channels with at least seven subfamilies. The variety of
      subfamilies corresponds to the differences in the activation mechanisms and
      functions. TRPM3 (TRP melastatin 3) and TRPV4 (TRP vanilloid 3) have been
      characterized as cation channels activated by extracellular hypo-osmoticity. In
      addition, TRPV4 is activated by metabolites of arachidonic acid as well as alpha
      isomers of phorbol esters known to be ineffective in stimulating proteins of the
      protein kinase C family. TRPM3 is responsive to sphingosine derivatives. The
      detection of splice variants with probably different activation mechanisms
      supports the idea that TRPM3 may have diverse cellular functions depending on the
      expression of a particular variant. The expression of TRPV4 in many epithelial
      cell types raised the question of the role of TRPV4 in epithelial physiology.
      Single-cell experiments as well as approaches using epithelial layers show that
      multiple cellular responses are triggered by TRPV4 activation and subsequent
      elevation of intracellular calcium. The TRPV4-induced responses increasing
      transcellular ion flux as well as paracellular permeability may allow the cells
      to adjust to changes in extracellular osmolarity. In summary, TRPV4 plays a
      central role in epithelial homoeostasis by modulating epithelial barrier
      function.

PMID- 17233611
TI  - TRPC1: a core component of store-operated calcium channels.
AB  - The TRPC (transient receptor potential canonical) proteins are activated in
      response to agonist-stimulated PIP(2) (phosphatidylinositol 4,5-bisphosphate)
      hydrolysis and have been suggested as candidate components of the elusive SOC
      (store-operated calcium channel). TRPC1 is currently the strongest candidate
      component of SOC. Endogenous TRPC1 has been shown to contribute to SOCE (store
      operated calcium entry) in several different cell types. However, the mechanisms
      involved in the regulation of TRPC1 and its exact physiological function have yet
      to be established. Studies from our laboratory and several others have
      demonstrated that TRPC1 is assembled in a signalling complex with key calcium
      signalling proteins in functionally specific plasma membrane microdomains.
      Furthermore, critical interactions between TRPC1 monomers as well as interactions
      between TRPC1 and other proteins determine the surface expression and function of
      TRPC1-containing channels. Recent studies have revealed novel regulators of TRPC1
      containing SOCs and have demonstrated a common molecular basis for the regulation
      of CRAC (calcium-release-activated calcium) and SOC channels. In the present
      paper, we will revisit the role of TRPC1 in SOCE and discuss how studies with
      TRPC1 provide an experimental basis for validating the mechanism of SOCE.

PMID- 17233612
TI  - Bipolar phospholipid sensing by TRPC5 calcium channel.
AB  - TRPC5 [TRP (transient receptor potential) canonical (or classical) 5] is a widely
      expressed mammalian homologue of Drosophila TRP, forming a calcium- and sodium
      permeable channel in the plasma membrane either as a homomultimer or
      heteromultimer with other proteins (e.g. TRPC1). Although several factors are
      known to stimulate the channel, understanding of its endogenous activators and
      functions is limited. This paper provides a brief and focused review of our
      latest findings that show that TRPC5 is a sensor of important signalling
      phospholipids, including lysophosphatidylcholine and sphingosine 1-phosphate,
      acting extracellularly or intracellularly. Underlying mechanisms of action and
      biological relevance are discussed.

PMID- 17233613
TI  - Regulation of TRP channels: a voltage-lipid connection.
AB  - TRP (transient receptor potential) channels respond to a plethora of stimuli in a
      fine-tuned manner. We show here that both membrane potential and the level of PI
      (phosphatidylinositol) phosphates are efficient regulators of TRP channel gating.
      Recent work has shown that this regulation applies to several members of the TRPV
      (TRP vanilloid) subfamily (TRPV1 and TRPV5) and the TRPM (TRP melastatin)
      subfamily (TRPM4/TRPM5/TRPM7/TRPM8), whereas regulation of members of the TRPC
      subfamily is still disputed. The mechanism whereby PIP(2) (PI 4,5-bisphosphate)
      acts on TRPM4, a Ca(2+)- and voltage-activated channel, is shown in detail in
      this paper: (i) PIP(2) may bind directly to the channel, (ii) PIP(2) induces
      sensitization to activation by Ca(2+), and (iii) PIP(2) shifts the voltage
      dependence towards negative and physiologically more meaningful potentials. A
      PIP(2)-binding pocket seems to comprise a part of the TRP domain and especially
      pleckstrin homology domains in the C-terminus.

PMID- 17233614
TI  - Regulation of calcium signalling by adenine-based second messengers.
AB  - cADPR [cyclic ADPR (ADP-ribose)], NAADP (nicotinic acid-adenine dinucleotide
      phosphate) and ADPR belong to the family of adenine-containing second messengers.
      They are metabolically related and are all involved in the regulation of cellular
      Ca(2+) homoeostasis. Activation of specific plasma membrane receptors is
      connected to cADPR formation in many cell types and tissues. In contrast receptor
      mediated formation of NAADP and ADPR has been shown only in a few selected
      cellular systems. The intracellular Ca(2+) channel triggered by cADPR is the RyR
      (ryanodine receptor); in the case of NAADP, both activation of RyR and a novel
      Ca(2+) channel have been proposed. In contrast, ADPR opens the non-specific
      cation channel TRPM2 [TRP (transient receptor potential) melastatin 2] that
      belongs to the TRP family of ion channels.

PMID- 17233615
TI  - Concerted action of associated proteins in the regulation of TRPV5 and TRPV6.
AB  - Ca(2+) is an essential ion in all organisms and many physiological functions in
      the body rely on the exact maintenance of the Ca(2+) balance. The epithelial
      Ca(2+) channels TRPV5 [TRP (transient receptor potential) vanilloid 5] and TRPV6
      are the most Ca(2+)-selective members of the TRP superfamily and are generally
      considered as the gatekeepers of Ca(2+) entry across epithelia. TRPV5 is involved
      in Ca(2+) reabsorption from pro-urine, while TRPV6 has an essential role in
      intestinal Ca(2+) uptake. These channels are the prime targets of calciotropic
      hormonal regulation, including vitamin D and parathyroid hormone. In addition,
      extra- and intra-cellular signalling by associated proteins and Ca(2+) itself
      play key roles in TRPV5 and TRPV6 regulation. In this paper, we describe the
      present understanding of the concerted action of calbindin-D(28k), klotho and
      BSPRY (B-box and SPRY-domain-containing protein) at different levels throughout
      the epithelial cell to control Ca(2+) influx at the luminal entry gate.

PMID- 17233616
TI  - Biological functions of TRPs unravelled by spontaneous mutations and transgenic
      animals.
AB  - The identification of the biological functions of TRP (transient receptor
      potential) proteins requires genetic approaches because a selective TRP channel
      pharmacology to unravel the roles of TRPs is not available so far for most TRPs.
      A survey is therefore presented of transgenic animal models carrying mutations in
      TRP genes, as well as of those TRP genes that when mutated result in human
      disease; the chromosomal locations of TRP channel genes in the human and mouse
      are also presented.

PMID- 17233617
TI  - TRP channels and kidney disease: lessons from polycystic kidney disease.
AB  - Important insights in to the function of members of the TRP (transient receptor
      potential) channel superfamily have been gained from the identification of
      disease-related mutations. In particular the identification of mutations in the
      PKD2 gene in autosomal dominant polycystic kidney disease has revealed a link
      between TRP channel function, mechanosensation and the role of the primary cilium
      in renal cyst formation. The PKD2 gene encodes TRPP2 (transient receptor
      potential polycystin 2) that has significant homology to voltage-activated
      calcium and sodium TRP channels. It interacts with polycystin-1 to form a large
      membrane-associated complex that is localized to the renal primary cilium.
      Functional characterization of this polycystin complex reveals that it can
      respond to mechanical stimuli such as flow, resulting in influx of extracellular
      calcium and release of calcium from intracellular stores. TRPP2 is expressed in
      the endoplasmic reticulum/sarcoplasmic reticulum where it also regulates
      intracellular calcium signalling. Therefore TRPP2 modulates many cellular
      processes via intracellular calcium-dependent signalling pathways.

PMID- 17233618
TI  - TRPM channel function in Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans contains over 20 genes for TRP (transient
      receptor potential) channels which include members of all of the subclasses
      identified in mammalian cells. These proteins include three members of the TRPM
      (TRP melastatin) family: gon-2 (abnormal gonad development), gtl-1 (gon-2-like 1)
      and gtl-2. Although studies of these genes are at an early stage, we are
      beginning to understand their functions in the life of C. elegans. Mutations in
      gon-2 have defective gonad formation because of failures in the cell division of
      the somatic gonad precursor cells. gon-2 and gtl-1 are both expressed in the
      intestine of the animal. Experiments on gon-2,gtl-1 double mutants show that they
      have a severe growth defect that is ameliorated by the addition of high levels of
      Mg(2+) to the growth medium. gon-2,gtl-1 double mutants have defective magnesium
      homoeostasis and also have altered sensitivity to toxic levels of Ni(2+).
      Furthermore gon-2 mutants have reduced levels of I(ORCa) (outwardly rectifying
      calcium current) in the intestinal cells. Thus these two channels appear to play
      an important role in cation homoeostasis in C. elegans. In addition, perturbing
      the function of gon-2 and gtl-1 disrupts the ultradian defecation rhythm in C.
      elegans, suggesting that these channels play an important role in regulating this
      calcium-dependent rhythmic process. The tractability of C. elegans as an
      experimental animal and its amenability to techniques such as RNAi (RNA
      interference) and in vivo imaging make it an excellent system for an integrative
      analysis of TRPM function.

PMID- 17233619
TI  - Differential role of TRP channels in prostate cancer.
AB  - A major clinical problem with PC (prostate cancer) is the cell's ability to
      survive and proliferate upon androgen withdrawal. Indeed, deregulated cell
      differentiation and proliferation, together with the suppression of apoptosis,
      provides the condition for abnormal tissue growth. Here, we examine the
      differential role of TRP (transient receptor potential) channels in the control
      of Ca(2+) homoeostasis and growth of PC cells.

PMID- 17233620
TI  - Interactions of PIN and PGP auxin transport mechanisms.
AB  - Polarized transport of the plant hormone auxin influences multiple growth
      processes in plants and is regulated by plasma-membrane-localized efflux and
      uptake carriers. The PGP (P-glycoprotein) ABC transporters (ATP-binding-cassette
      transporters), PIN (pin-formed) subfamily of major facilitator proteins and
      members of AUX/LAX families have been shown to independently transport auxin both
      in planta and in heterologous systems. However, PIN- and PGP-mediated transport
      in heterologous systems exhibits decreased substrate specificity and inhibitor
      sensitivity compared with what is seen in plants and plant cells. To determine
      whether PIN-PGP interactions enhance transport specificity, we analysed
      interactions of the representative auxin-transporting PGPs with PIN1 and AUX1 in
      planta and in heterologous systems. Here, we provide evidence that PINs and PGPs
      interact and function both independently and co-ordinately to control polar auxin
      transport and impart transport specificity and directionality. These interactions
      take place in protein complexes stabilized by PGPs in detergent-resistant
      microdomains.

PMID- 17233621
TI  - Plasmodesmata and intercellular transport of viral RNA.
AB  - Cell-to-cell communication in plants involves the symplastic trafficking of
      informational protein and RNA macromolecules through cytoplasmic bridges in the
      plant cell wall known as plasmodesmata. Viruses exploit this route for the spread
      of infection and are used as a model to study the mechanisms by which
      macromolecules are targeted to the pore. Studies using tobacco mosaic virus have
      led to the identification of host components that participate in plasmodesmal
      targeting of viral RNA and movement protein.

PMID- 17233622
TI  - Epidermal pattern formation in the root and shoot of Arabidopsis.
AB  - Root hair formation, stomata development on hypocotyls and trichome formation on
      leaves in Arabidopsis represent three model systems for epidermal patterning in
      plants that involve a common set of genes or corresponding homologues. The
      resulting pattern and the developmental readout are, however, strikingly
      different. Trichomes become regularly spaced on the leaf surface. Root hairs and
      stomata-bearing cells are formed in rows at specific locations with reference to
      the underlying cortex cells. In this review, we summarize the mechanistic
      similarities and discuss differences that might account for the different outcome
      of patterning in each system.

PMID- 17233623
TI  - Planar polarity of root hair positioning in Arabidopsis.
AB  - The co-ordinated polarity of cells within the plane of a single tissue layer
      (planar polarity) is intensively studied in animal epithelia but has only
      recently been systematically analysed in plants. The polar positioning of hairs
      in the root epidermis of Arabidopsis thaliana provides an easily accessible
      system for the functional dissection of a plant-specific planar polarity.
      Recently, mutants originally isolated in genetic screens for defects in root hair
      morphogenesis and changes in the sensitivity to or the production of the plant
      hormones auxin and ethylene have identified players that contribute to polar root
      hair placement. Here, we summarize and discuss recent progress in research on
      polar root hair positioning from studies in Arabidopsis.

PMID- 17233624
TI  - Cell signalling during vascular morphogenesis.
AB  - Vascular tissue in plants is unique due to its diverse and dynamic cellular
      patterns. Through research in several organisms, such as Arabidopsis, Populus and
      Zinnia, using biochemical, genetic and genomic approaches, significant progress
      has recently been made in revealing the molecular nature of several signals
      underlying the patterning of vascular tissue. These signals include ligands,
      receptors and transcriptional regulators. The future challenge is to understand
      how the identified signals work together to control vascular morphogenesis.

PMID- 17233625
TI  - Signalling during epidermal development.
AB  - The process of L1 specification early in plant embryogenesis, and subsequent
      maintenance and elaboration of epidermal organization, are fundamental to plant
      growth and fitness. To occur in a co-ordinated fashion, these processes require
      considerable cell-cell cross-talk. It is perhaps then unsurprising that several
      classes of plant RLKs (receptor-like kinases), as well as other membrane
      localized signalling components, have been implicated both in epidermal
      specification and in patterning events governing the distribution of epidermal
      cell types. However, despite our growing knowledge of the roles of these
      signalling molecules, remarkably little is understood regarding their function at
      the cellular level. In particular the potential role of regulated proteolytic
      cleavage in controlling the activity of signalling molecules at the plant plasma
      membrane has remained largely unaddressed despite its massive importance in
      signalling in animal systems. Because of the relative physical accessibility of
      their expression domains, molecules involved in epidermal development present
      opportunities for investigating mechanisms of cell-cell signalling in planta.
      Advances in understanding the potential regulatory processing of membrane
      localized signalling molecules during epidermal development will be examined
      using parallels with animal systems to highlight potential future directions for
      this field of research.

PMID- 17233626
TI  - Reprogramming of root epidermal cells in response to nutrient deficiency.
AB  - Post-embryonic development of the root system is highly plastic to environmental
      cues, compensating for the sessile lifestyle of plants. The fate of epidermal
      cells of Arabidopsis roots is particularly responsive to nutritional signals,
      leading to an increase in the root's surface area in the absence of the essential
      but immobile minerals iron, phosphate and manganese. The resulting phenotype is
      characteristic of the respective condition. Growth under nutrient starvation
      affects the expression of genes involved in cell specification, indicating that
      environmental signals are perceived at an early stage of cell development. Cell
      fate decisions are controlled at different levels, probably integrated at the
      level of chromatin organization.

PMID- 17233628
TI  - Acid-base catalysis in Leuconostoc mesenteroides sucrose phosphorylase probed by
      site-directed mutagenesis and detailed kinetic comparison of wild-type and Glu237
      ->Gln mutant enzymes.
AB  - The role of acid-base catalysis in the two-step enzymatic mechanism of alpha
      retaining glucosyl transfer by Leuconostoc mesenteroides sucrose phosphorylase
      has been examined through site-directed replacement of the putative catalytic
      Glu237 and detailed comparison of purified wild-type and Glu237-->Gln mutant
      enzymes using steady-state kinetics. Reactions with substrates requiring Bronsted
      catalytic assistance for glucosylation or deglucosylation were selectively slowed
      at the respective step, about 10(5)-fold, in E237Q. Azide, acetate and formate
      but not halides restored catalytic activity up to 300-fold in E237Q under
      conditions in which the deglucosylation step was rate-determining, and promoted
      production of the corresponding alpha-glucosides. In situ proton NMR studies of
      the chemical rescue of E237Q by acetate and formate revealed that enzymatically
      formed alpha-glucose 1-esters decomposed spontaneously via acyl group migration
      and hydrolysis. Using pH profiles of kcat/K(m), the pH dependences of kinetically
      isolated glucosylation and deglucosylation steps were analysed for wild-type and
      E237Q. Glucosylation of the wild-type proceeded optimally above and below
      apparent pK(a) values of about 5.6 and 7.2 respectively whereas deglucosylation
      was dependent on the apparent single ionization of a group of pK(a) approximately
      5.8 that must be deprotonated for reaction. Glucosylation of E237Q was slowed
      below apparent pK(a) approximately 6.0 but had lost the high pH dependence of the
      wild-type. Deglucosylation of E237Q was pH-independent. The results allow
      unequivocal assignment of Glu237 as the catalytic acid-base of sucrose
      phosphorylase. They support a mechanism in which the pK(a) of Glu237 cycles
      between approximately 7.2 in free enzyme and approximately 5.8 in glucosyl enzyme
      intermediate, ensuring optimal participation of the glutamate residue side chain
      at each step in catalysis. Enzyme deglucosylation to an anionic nucleophile took
      place with Glu237 protonated or unprotonated. The results delineate how conserved
      active-site groups of retaining glycoside hydrolases can accommodate enzymatic
      function of a phosphorylase.

PMID- 17233627
TI  - Does the calcein-AM method assay the total cellular 'labile iron pool' or only a
      fraction of it?
AB  - The calcein-AM (calcein-acetoxymethyl ester) method is a widely used technique
      that is supposed to assay the intracellular 'labile iron pool' (LIP). When cells
      in culture are exposed to this ester, it passes the plasma membrane and reacts
      with cytosolic unspecific esterases. One of the reaction products, calcein, is a
      fluorochrome and a hydrophilic alcohol to which membranes are non-permeable and
      which, consequently, is retained within the cytosol of cells. Calcein
      fluorescence is quenched following chelation of low-mass labile iron, and the
      degree of quenching gives an estimate of the amounts of chelatable iron. However,
      a requirement for the assay to be able to demonstrate cellular LIP in total is
      that such iron be localized in the cytosol and not in a membrane-limited
      compartment. For some time it has been known that a major part of cellular, redox
      active, labile, low-mass iron is temporarily localized in the lysosomal
      compartment as a result of the autophagic degradation of ferruginous materials,
      such as mitochondrial complexes and ferritin. Even if some calcein-AM may escape
      cytosolic esterases and enter lysosomes to be cleaved by lysosomal acidic
      esterases, the resulting calcein does not significantly chelate iron at <pH 5. In
      the present study we show that the calcein-AM method does not capture lysosomal
      low-mass iron and, therefore, that the method seriously underestimates total
      cellular labile iron.

PMID- 17233629
TI  - First step of the cell-penetrating peptide mechanism involves Rac1 GTPase
      dependent actin-network remodelling.
AB  - BACKGROUND INFORMATION: Application of CPPs (cell-penetrating peptides)
      constitutes a promising strategy for the intracellular delivery of therapeutic
      molecules. The non-covalent approach based on the amphipathic peptide MPG has
      been successfully used to improve the delivery of biologically active
      macromolecules, both in cellulo and in vivo, through a mechanism independent of
      the endosomal pathway and mediated by the membrane potential. RESULTS: In the
      present study, we have investigated the first step of the cellular uptake
      mechanism of MPG and shown that both MPG and MPG-cargo complexes interact with
      the extracellular matrix through the negatively charged heparan sulfate
      proteoglycans. We demonstrated that initiation of cellular uptake constitutes a
      highly dynamic mechanism where the binding of MPG or the MPG-cargo to the
      extracellular matrix is rapidly followed by a remodelling of the actin network
      associated with the activation of the GTPase Rac1. We suggest that MPG-induced
      clustering of the glycosaminoglycan platform constitutes the 'onset' of the
      cellular uptake mechanism, thereby increasing membrane dynamics and membrane
      fusion processes. This process favours cell entry of MPG or MPG-DNA complexes,
      which is further controlled by the ability of MPG to induce a local membrane
      destabilization. CONCLUSIONS: Although CPPs are taken up through different
      pathways and mechanisms, the initial step involves electrostatic interactions
      with the glycosaminoglycan platform, and the dynamics of associated membrane
      microdomains can be generalized to most non-viral delivery systems.

PMID- 17233630
TI  - Paxillin family members function as Csk-binding proteins that regulate Lyn
      activity in human and murine platelets.
AB  - SFKs (Src family kinases) contribute importantly to platelet function in
      haemostasis. SFK activity is controlled by Csk (C-terminal Src kinase), which
      phosphorylates a C-terminal tyrosine residue on SFKs, resulting in inhibition of
      SFK activity. Csk is recruited to sites of SFK activity by tyrosine
      phosphorylated Csk-binding proteins. Paxillin, a multidomain adaptor protein, has
      been shown to act as a Csk-binding protein and to inhibit Src activity during
      growth factor signalling. Human platelets express Hic-5, a member of the paxillin
      family; however, its ability to act as a Csk-binding protein has not been
      characterized. We sought to identify and characterize the ability of paxillin
      family members to act as Csk-binding proteins during platelet activation. We
      found that murine and human platelets differ in the complement of paxillin family
      members expressed. Human platelets express Hic-5, whereas murine platelets
      express paxillin and leupaxin in addition to Hic-5. In aggregating human
      platelets, Hic-5 was tyrosine phosphorylated and recruited Csk via its SH2
      domains. In aggregating murine platelets, however, Csk bound preferentially to
      paxillin, even though both paxillin and Hic-5 were abundantly present and became
      tyrosine phosphorylated. The SFK Lyn, but not Src or Fyn, was associated with
      paxillin family members in resting and aggregated human and murine platelets.
      Lyn, however, was phosphorylated on its C-terminal inhibitory tyrosine residue
      only following platelet aggregation, which was coincident with recruitment of Csk
      to paxillin and/or Hic-5 in a manner dependent on prior alpha(IIb)beta3
      engagement. These observations support the notion that Hic-5 and paxillin
      function as negative feedback regulators of SFKs in aggregated platelets and
      that, when both are present, paxillin is preferentially used.

PMID- 17233631
TI  - Evaluation of viral removal by nanofiltration using real-time quantitative
      polymerase chain reaction.
AB  - Nanofiltration is commonly introduced into purification processes of biologics
      produced in mammalian cells to serve as a designated step for removal of
      potential exogenous viral contaminants and endogenous retrovirus-like particles.
      The LRV (log reduction value) achieved by nanofiltration is often determined by
      cell-based infectivity assay, which is time-consuming and labour-intensive. We
      have explored the possibility of employing QPCR (quantitative PCR) to evaluate
      LRV achieved by nanofiltration in scaled-down studies using two model viruses,
      namely xenotropic murine leukemia virus and murine minute virus. We report here
      the successful development of a QPCR-based method suitable for quantification of
      virus removal by nanofiltration. The method includes a nuclease treatment step to
      remove free viral nucleic acids, while viral genome associated with intact virus
      particles is shielded from the nuclease. In addition, HIV Armored RNA was
      included as an internal control to ensure the accuracy and reliability of the
      method. The QPCRbased method described here provides several advantages such as
      better sensitivity, faster turnaround time, reduced cost and higher throughput
      over the traditional cell-based infectivity assays.

PMID- 17233632
TI  - The European networking for combating meningococcal disease.

PMID- 17233633
TI  - Conquering the meningococcus.
AB  - Since the first outbreaks of meningococcal meningitis were first described in
      Geneva in 1804 and in New England in 1806, and since the discovery of the
      causative agent by Weichselbaum in 1887 and the beginning of epidemics of
      meningococcal meningitis in the sub-Saharan Africa approximately 100 years ago,
      Neisseria meningitidis has been recognized as the cause worldwide of epidemic
      meningitis and meningococcemia. The massive epidemic outbreaks in sub-Saharan
      Africa in the 1990's, the emergence since 1995 of serogroups Y, W-135 and X and
      the prolonged outbreak of serogroup B meningococcal disease in New Zealand over
      the last decade serve to remind us of the continued potential of the
      meningococcus to cause global morbidity and mortality. This report reviews new
      discoveries impacting prevention and future prospects for conquering the
      meningococcus as a human pathogen.

PMID- 17233634
TI  - Quality assessed nonculture techniques for detection and typing of meningococci.
AB  - PCR protocols are increasingly used in laboratories worldwide for the diagnosis
      and confirmation of invasive meningococcal infection. Protocols are now available
      for the identification of Neisseria meningitidis, for genogrouping,
      susceptibility to antibiotics and genotyping of the corresponding isolates. The
      implementation of quality assurance (QA) schemes and standardization of protocols
      are required. Diagnostic and confirmatory PCRs should perform consistently in
      clinical and reference microbiology laboratories. General QA schemes address the
      issues of sample preparation, PCR laboratory environment, equipment and
      validation of protocols. Moreover, external QA interlaboratory studies are
      essential. The European Monitoring Group on Meningococci has provided a good
      forum to conduct such studies through the development and distribution of samples
      and protocols for nonculture detection and typing of N. meningitidis.

PMID- 17233635
TI  - Lessons from meningococcal carriage studies.
AB  - Neisseria meningitidis, an obligate commensal of humans, normally colonizes the
      mucosa of the upper respiratory tract without affecting the host, a phenomenon
      known as carriage. In Europe, as much as 35% of young adults are carriers at a
      given time. Recent studies using molecular methods for clone identification have
      demonstrated the extensive genetic diversity of the strains isolated from
      carriers, in comparison with a limited number of hypervirulent strains associated
      with invasive disease. Published studies and new data generated through the
      framework of the EU-MenNet clearly indicated significant differences in
      pathogenicity between meningococcal clones and in the distribution of multilocus
      sequence types among isolates from asymptomatic carriers among European
      countries; simultaneous carriage of more than one meningococcal strain in the
      throat is rare, but occasionally occurs; and the commensal association of
      particular clones with a host is a long-term relationship, often lasting several
      months. Further investigations of the carrier state are warranted to improve our
      understanding of the epidemiology and pathogenesis of meningococcal disease, as
      well as to support the introduction and to measure the impact of mass
      vaccination.

PMID- 17233636
TI  - Diagnosis and management of meningococcal disease: the need for centralized care.
AB  - Meningococcal infection remains a significant health problem in children, with a
      significant mortality and morbidity. Prompt recognition and aggressive early
      treatment are the only effective measures against invasive disease. This requires
      immediate administration of antibiotic therapy, and the recognition and treatment
      of patients who may have complications of meningococcal infection such as shock,
      raised intracranial pressure (ICP) or both. Encouragingly, its mortality has
      fallen in recent years. This is the result of several factors such as the
      centralization of care of seriously ill children in paediatric intensive care
      units (PICUs), the establishment of specialized mobile intensive care teams, the
      development of protocols for the treatment of meningococcal infection, and the
      dissemination by national bodies and charities of guidance about early
      recognition and management. We will review the pathophysiology and management of
      the different presentations of meningococcal disease and examine the possible
      role of adjunctive therapies.

PMID- 17233637
TI  - Mouse inbred strain differences in ethanol drinking to intoxication.
AB  - Recently, we described a simple procedure, Drinking in the Dark (DID), in which
      C57BL/6J mice self-administer ethanol to a blood ethanol concentration (BEC)
      above 1 mg/ml. The test consists of replacing the water with 20% ethanol in the
      home cage for 4 h early during the dark phase of the light/dark cycle. Three
      experiments were conducted to explore this high ethanol drinking model further.
      In experiment 1, a microanalysis of C57BL/6J behavior showed that the pattern of
      ethanol drinking was different from routine water intake. In experiment 2,
      drinking impaired performance of C57BL/6J on the accelerating rotarod and balance
      beam. In experiment 3, 12 inbred strains were screened to estimate genetic
      influences on DID and correlations with other traits. Large, reliable differences
      in intake and BEC were detected among the strains, with C57BL/6J showing the
      highest values. Strain means were positively correlated with intake and BEC in
      the standard (24 h) and a limited (4 h) two-bottle ethanol vs. water test, but
      BECs reached higher levels for DID. Strain mean correlations with other traits in
      the Mouse Phenome Project database supported previously reported genetic
      relationships of high ethanol drinking with low chronic ethanol withdrawal
      severity and low ethanol-conditioned taste aversion. We extend these findings by
      showing that the correlation estimates remain relatively unchanged even after
      correcting for phylogenetic relatedness among the strains, thus relaxing the
      assumption that the strain means are statistically independent. We discuss
      applications of the model for finding genes that predispose pharmacologically
      significant drinking in mice.

PMID- 17233638
TI  - Evidence for non-genomic transmission of ecological information via maternal
      behavior in female rats.
AB  - Maternal behavior is flexible and programs offspring development. Using a novel
      manipulation, we demonstrate that rat maternal behavior is sensitive to
      ecologically relevant stimuli. Long-Evans hooded rat dams (F0) and pups were
      exposed to a predator condition (cat odor) or a control condition (no odor) for 1
      h on the day of parturition. Predator-exposed F0 dams displayed significantly
      more maternal behavior (licking/grooming, arched-back nursing) relative to
      control-exposed dams across five subsequent observation days. Female offspring
      (F1) were raised to adulthood, bred and maternal behavior was observed. F1 dams
      reared by a predator-exposed F0 dam displayed significantly higher maternal
      behavior relative to F1 dams reared by a control-exposed F0 dam across 5 days of
      observation. Increased levels of maternal behavior in predator-reared (PR) F1
      dams were evident even in F1 females that had been cross-fostered (CF) from a
      control-exposed F0 dam, suggesting a non-genomic transmission of increased levels
      of maternal behavior. Lactating PR F1 dams had significantly elevated estrogen
      receptor alpha and beta mRNA in the medial preoptic area relative to control
      reared (CR) F1 dams. Furthermore, among CR F1 dams, there was no significant
      difference between those dams that had been CF from predator-exposed F0 dams and
      those that had been sham CF. These results support the hypothesis that flexible
      rat maternal behavior can shape offspring development according to current
      environmental conditions. The results also suggest that estrogen signaling may be
      part of an epigenetic mechanism by which changes in maternal behavior are passed
      from F0 to F1 dams.

PMID- 17233639
TI  - Estimating wall guidance and attraction in mouse free locomotor behavior.
AB  - In this study, we estimate the influence exerted by the wall of the Open Field on
      the trajectory of the mouse. The wall exerts two types of influence on the
      mouse's path: one of guidance and one of attraction. The guiding influence is
      expressed by the tendency of mice to progress in parallel to the wall. This
      tendency wanes with increasing distance from the wall but is observed at large
      distances from it. The more parallel the mouse is to the wall the higher is its
      speed, even when distant from the wall. This association between heading
      direction and speed shows that the mouse controls its heading in reference to the
      wall. It is also observed in some blind strains, revealing that wall-guidance is
      not based exclusively on vision. The attraction influence is reflected by
      movement along the wall and by the asymmetry between speed during movement
      toward, and during movement away from the wall: sighted mice move faster toward
      the wall, whereas blind mice use similar speeds in both directions. Measures
      characterizing these influences are presented for five inbred strains, revealing
      heritable components that are replicable across laboratories. The revealed
      structure can lead to the identification of distinct groups of genes that mediate
      the distinct influences of guidance and attraction exerted by the wall. It can
      also serve as a framework for the decoding of electrophysiological data recorded
      in free moving rodents in the Open Field.

PMID- 17233640
TI  - Mutations in dynamin-related protein result in gross changes in mitochondrial
      morphology and affect synaptic vesicle recycling at the Drosophila neuromuscular
      junction.
AB  - Mitochondria are the primary source of ATP needed for the steps of the synaptic
      vesicle cycle. Dynamin-related protein (DRP) is involved in the fission of
      mitochondria and peroxisomes. To assess the role of mitochondria in synaptic
      function, we characterized a Drosophila DRP mutant combination that shows an
      acute temperature-sensitive paralysis. Sequencing of the mutant reveals a single
      amino acid change in the guanosine triphosphate hydrolysing domain (GTPase
      domain) of DRP. The synaptic mitochondria in these mutants are remarkably
      elongated, suggesting a role for DRP in mitochondrial fission in Drosophila.
      There is a loss of neuronal transmission at restrictive temperatures in
      electroretinogram (ERG) recordings. Like stress-sensitive B (sesB), a
      mitochondrial adenosine triphosphate (ATP) translocase mutant we studied earlier
      for its effects on synaptic vesicle recycling, an allele-specific reduction in
      the temperature of paralysis of Drosophila synaptic vesicle recycling mutant
      shibire was seen in the DRP mutant background. These data, in addition to
      depletion of vesicles observed in electron microscopic sections of photoreceptor
      synapses at restrictive temperatures, suggest a block in synaptic vesicle
      recycling due to reduced mitochondrial function.

PMID- 17233641
TI  - Impaired spatial learning in the APPSwe + PSEN1DeltaE9 bigenic mouse model of
      Alzheimer's disease.
AB  - Mice co-expressing the Swedish amyloid precursor protein mutation (APP(Swe)) and
      exon 9 deletion (DeltaE9) of the PSEN1 gene begin to develop amyloid plaques at 6
      7 months of age. We demonstrate here a spatial learning deficit in 7-month-old
      APP(Swe) + PSEN1DeltaE9 bigenic mice using an adaptation of the Barnes maze. Mice
      were first trained on a cued target followed by a hidden-target condition.
      Although bigenic mice quickly learned the cued-target version of the task, they
      were significantly impaired when switched to the hidden-target version. In
      contrast, a separate group of double-transgenic mice trained first on the spatial
      hidden-target version of the task were unimpaired relative to wild-type controls.
      We propose that processes such as general rule learning, context learning and
      exploratory habituation exert a greater influence when the testing environment is
      novel and overshadow the spatial memory deficit in naive bigenic mice. However,
      when cued-target training is conducted first, these processes habituate and the
      spatial learning deficit is unmasked. Seven-month-old APP(Swe) + PSEN1DeltaE9
      mice were unimpaired on tests of memory that did not involve learning the rules
      governing spatial associations.

PMID- 17233642
TI  - Heritable risk factors associated with language impairments.
AB  - There is a strong genetic contribution to children's language and literacy
      impairments. The aim of this study was to determine which aspects of the
      phenotype are familial by comparing 34 parents of probands with language/literacy
      impairments and 33 parents of typically developing probands. The parents
      responded to questionnaires regarding previous history for language/reading
      impairment and participated in psychometric testing. The psychometric test
      battery consisted of tests assessing non-verbal IQ, short-term memory,
      articulation, receptive grammar, reading abilities and spelling. Self-report
      measures demonstrated a higher prevalence of language and literacy impairments in
      parents of affected probands (32%) compared with parents of unaffected probands
      (6%). The two groups of parents differed significantly in their performance on
      the non-word repetition, oromotor and digit span tasks. Non-word repetition gave
      the best discrimination between the parent groups even when the data from the
      parents who actually were impaired as ascertained by direct testing or self
      report were removed from the analyses. This suggests that non-word repetition
      serves as a marker of a family risk for language impairment. The paper concludes
      with a discussion of issues associated with ascertainment of specific language
      impairment (SLI).

PMID- 17233644
TI  - Directly observed therapy and tuberculosis: how can a systematic review of
      qualitative research contribute to improving services? A qualitative meta
      synthesis.
AB  - AIM: This paper reports the findings from a qualitative meta-synthesis concerning
      people with, or at risk of, tuberculosis, service providers and policymakers and
      their experiences and perceptions of tuberculosis and treatment. BACKGROUND:
      Directly observed therapy is part of a package of interventions to improve
      tuberculosis treatment and adherence. A Cochrane systematic review of trials
      showed an absence of evidence for or against directly observed therapy compared
      with people treating themselves. METHOD: Qualitative systematic review methods
      were used to search, screen, appraise and extract data thematic analysis was used
      to synthesize data from 1990 to 2002, and an update of literature to December
      2005. Two questions were addressed: 'What does qualitative research tell us about
      the facilitators and barriers to accessing and complying with tuberculosis
      treatment?' and 'What does qualitative research tell us about the diverse results
      and effect sizes of the randomized controlled trials included in the Cochrane
      review?' Findings help explain the diverse trial results in a Cochrane systematic
      review of directly observed therapy and tuberculosis and consider implications
      for research, policy and practice. FINDINGS: Five themes emerged from the 1990 to
      2002 synthesis: socio-economic circumstances, material resources and individual
      agency; explanatory models and knowledge systems in relation to tuberculosis and
      its treatment; the experience of stigma and public discourses around
      tuberculosis; sanctions, incentives and support, and the social organization and
      social relationships of care. Two additional themes emerged from the 2005 update.
      CONCLUSION: The qualitative meta-synthesis improved the relevance and scope of
      the Cochrane review of trials. The findings make a major contribution to the
      development of theory concerning global WHO-branded disease control and the
      practicality of local delivery to people.

PMID- 17233643
TI  - Possible association of beta-arrestin 2 gene with methamphetamine use disorder,
      but not schizophrenia.
AB  - Recent investigations suggest that the AKT/glycogen synthase kinase 3 (GSK3)
      signaling cascade may be associated with the pathophysiology of schizophrenia and
      methamphetamine (METH) use disorder. One important molecule related to this
      cascade is beta-arrestin 2 (ARRB2). We therefore conducted a genetic case-control
      association analysis of the gene for ARRB2 with schizophrenia and METH use
      disorder in a Japanese population (547 people with schizophrenia, 177 with METH
      use disorder and 546 controls). A possible association of 'tag single nucleotide
      polymorphisms (SNPs)' was found in METH use disorder (rs1045280: P(genotype) =
      0.0118, P(allele) = 0.00351; rs2036657: P(allele) = 0.0431; rs4790694:
      P(genotype) = 0.0167, P(allele) = 0.0202), but no association was found with
      schizophrenia. We also evaluated the gene-gene interactions among ARRB2, AKT1,
      and GSK3B, which we previously reported for each of these diseases. However, no
      interaction was seen in our samples. This is the first association analysis of
      ARRB2, and our results indicate that ARRB2 may play a role in the pathophysiology
      of METH use disorder.

PMID- 17233645
TI  - Continuity of care and general wellbeing of patients with comorbidities requiring
      joint replacement.
AB  - AIM: The aim of this paper is to examine the continuity of care and general
      wellbeing of patients with comorbidities undergoing elective total hip or knee
      joint replacement. BACKGROUND: Advances in medical science and improved
      lifestyles have reduced mortality rates in most Western countries. As a result,
      there is an ageing population with a concomitant growth in the number of people
      who are living with multiple chronic illnesses, commonly referred to as
      comorbidities. These patients often require acute care services, creating a blend
      of acute and chronic illness needs. For example, joint replacement surgery is
      frequently performed to improve impaired mobility associated with osteoarthritis.
      METHOD: A purposive sample of twenty participants with multiple comorbidities who
      required joint replacement surgery was recruited to obtain survey, interview and
      medical record audit data. Data were collected during 2004 and 2005. FINDINGS:
      Comorbidity care was poorly co-ordinated prior to having surgery, during the
      acute care stay and following surgery and primarily entailed prescribed
      medicines. The main focus in acute care was patient throughput following joint
      replacement surgery according to a prescribed clinical pathway. General wellbeing
      was less than optimal: participants reported pain, fatigue, insomnia and
      alterations in urinary elimination as the chief sources of discomfort during the
      course of the study. CONCLUSION: Continuity of care of comorbidities was lacking.
      Comorbidities affected patient general wellbeing and delayed recovery from
      surgery. Acute care, clinical pathways and the specialisation of medicine and
      nursing subordinated the general problem of patients with comorbidities. Systems
      designed to integrate and co-ordinate chronic illness care had limited
      application in the acute care setting. A multidisciplinary, holistic approach is
      required. Recommendations for further research conclude this paper.

PMID- 17233646
TI  - Improving paediatric nurses' knowledge and attitudes in childhood fever
      management.
AB  - AIM: This paper reports an evaluation of the effectiveness of a peer education
      programme in developing paediatric nurses' evidence-based knowledge and attitudes
      towards fever management and the sustainability of these changes. BACKGROUND: In
      general, paediatric nurses' fever management knowledge seems to be mediocre. They
      believe fever to be harmful, causing febrile convulsions and brain damage.
      Antipyretics are administered to prevent febrile convulsions and alternate
      antipyretics are given when temperatures are not reduced. METHOD: A quasi
      experiment was conducted from August 2002 to March 2003. An experimental group of
      Registered Nurses received the peer education programme and peer support and
      education were promoted for those unable to attend the sessions. A control group
      continued its normal practices. Seventy-seven nurses were eligible to attend the
      programme; 74.0% attended at least one session, 52% two or more. Questionnaire
      data were collected 1 month before and 1 and 4 months after the peer education
      programme from 56.3% to 77.8% of eligible experimental and 40.9% to 51.6% of
      eligible control group nurses. FINDINGS: Interaction effects between group and
      time were found in overall knowledge (P = 0.01), specifically knowledge of the
      physiology of fever (P = 0.001), and attitudes towards evidence-based fever
      management (P = 0.05). In addition, experimental group nurses demonstrated
      statistically significantly more knowledge of general fever management principles
      at 4 months after the intervention than control group nurses (P = 0.01), and
      compared with their own knowledge at baseline (P < 0.001). CONCLUSIONS:
      Educational programmes targeting practice change must be theoretically based and
      target knowledge, attitudes and barriers to change. The programme tested here,
      which incorporated peer education and support and facilitated group change, is
      adaptable to other practices, groups and settings.

PMID- 17233647
TI  - Evaluation of an osteoporosis prevention education programme for young adults.
AB  - AIM: This paper reports a study exploring the effectiveness of an osteoporosis
      prevention education programme for young adults. METHODS: A quasi-experimental
      study was carried out with two groups, using pre-, post- and follow-up measures
      and was conducted in one integrated services centre during the period July 2005
      to November 2005. RESULTS: The results showed statistically significant increases
      in the reported follow-up for each outcome: osteoporosis knowledge test scores,
      osteoporosis health brief scores, and osteoporosis self-efficacy scores, for
      those in the intervention group compared with those in the control group. On the
      satisfaction score, most participants in the intervention group rated the nurse's
      performance in the educational programme positively. CONCLUSION: Strategies used
      in this programme may provide guidance for the design of future programmes.

PMID- 17233648
TI  - What degree of work overload is likely to cause increased sickness absenteeism
      among nurses? Evidence from the RAFAELA patient classification system.
AB  - AIM: This paper reports a study examining whether nurses' work overload is
      associated with increased sick leave and quantifying the loss of working days
      from work overload. BACKGROUND: The RAFAELA patient classification system
      indicates nursing care intensity in relation to an optimum and is one of the few
      validated monitoring instruments of patient-associated workload among nurses.
      However, it is not clear whether work overload is a risk factor for increased
      sickness absenteeism, an important occupational problem in health care. METHOD:
      An observational cohort study was carried out with 877 nurses, 31 wards and five
      Finnish hospitals. Patient-associated workload scores from the RAFAELA system
      were based on a 6-month monitoring period in 2004. Records of 12-month self
      certified (1-3 days) and medically certified (>3 days) periods of sick leave in
      the same year were obtained from employers' registers. FINDINGS: The mean
      workload was 9% (sd = 8%) above the optimum. There was a linear trend between
      increasing workload and increasing sick leave (P < or = 0.006). Among nurses with
      workload > or =30% above the optimum the rate of self certified periods of sick
      leave was 1.44 (95% CI 1.13-1.83) times higher than among those with an optimum
      workload. The corresponding rate ratio for medically certified sick leave was
      1.49 (1.10-2.03). These excess rates of sickness absence resulted in 12 extra
      sick leave days per person-year. CONCLUSION: Measuring nurses' workload may be an
      important part of strategic human resource management of nurses to reduce sick
      leave among nurses.

PMID- 17233649
TI  - Globalization and the cultural safety of an immigrant Muslim community.
AB  - AIM: This paper reports a study the aim of which was to further understanding of
      cultural safety by focusing on the social health of a small immigrant community
      of Muslims in a relatively homogeneous region of Canada following the terror
      attacks on 11 September 2001 (9/11). BACKGROUND: The aftermath of 9/11 negatively
      affected Muslims living in many centers of Western Europe and North America.
      Little is known about the social health of Muslims in smaller areas with little
      cultural diversity. Developed by Maori nurses, the cultural safety concept
      captures the negative health effects of inequities experienced by the indigenous
      people of New Zealand. Nurses in Canada have used the concept to understand the
      health of Aboriginal peoples. It has also been used to investigate the nursing
      care of immigrants in a Canadian metropolitan centre. Findings indicated,
      however, that the dichotomy between culturally safe and unsafe groups was
      blurred. METHOD: The methodology was qualitative, based on the constructivist
      paradigm. A purposive sample of 26 Muslims of Middle Eastern, Indian or Pakistani
      origin and residing in the province of New Brunswick, Canada were interviewed in
      2002-2003. Findings. Participants experienced a sudden transition from cultural
      safety to cultural risk following 9/11. Their experience of cultural safety
      included a sense of social integration in the community and invisibility as a
      minority. Cultural risk stemmed from being in the spotlight of an international
      media and becoming a visible minority. CONCLUSION: Cultural risk is not
      necessarily rooted in historical events and may be generated by outside forces
      rather than by longstanding inequities in relationships between groups within the
      community. Nurses need to think about the cultural safety of their practices when
      caring for members of socially disadvantaged cultural minority groups as this may
      affect the health services delivered to them.

PMID- 17233650
TI  - Prevalence, self-efficacy and perceptions of conflicting advice and self
      management: effects of a breastfeeding journal.
AB  - AIM: This paper reports an assessment of the effects of a breastfeeding journal
      on breastfeeding prevalence and perceptions of conflicting advice, self
      management and self-efficacy. BACKGROUND: Breastfeeding prevalence rates in most
      developed countries are not meeting recommendations. Women's concerns about
      inconsistent advice, limited involvement in decision-making, accessibility of
      information and inappropriate follow-up have been recognized. Research on
      evaluation of interventions addressing these concerns and including antenatal and
      early postnatal periods is required. Method. An intervention study was conducted
      from July 2003 to April 2004, with control and intervention groups recruited
      sequentially. The intervention group received a breastfeeding journal at 36 weeks
      antenatally in breastfeeding classes that were attended at different times by
      intervention and control group members. The intervention and control groups were
      compared during postpartum hospitalization and 12 weeks for breastfeeding
      prevalence and perceptions of self-efficacy, conflicting advice and self
      management. FINDINGS: No statistically significant differences were noted between
      the intervention and control groups in breastfeeding prevalence at 12 weeks or
      self-efficacy during hospitalization. There was a statistically significant
      difference between groups in conflicting advice at both times. Although
      conflicting advice continues to present a dilemma for women, levels of
      conflicting advice did not explain breastfeeding self-efficacy. Breastfeeding
      self-management was a statistically significant contributor to breastfeeding
      prevalence prior to the addition of breastfeeding self-efficacy. CONCLUSIONS:
      Women's perceptions of their ability to manage and be actively involved in
      decision-making explained breastfeeding prevalence at 12-week postpartum. Efforts
      to encourage women's involvement in decision-making about breastfeeding are a
      useful strategy to promote breastfeeding.

PMID- 17233651
TI  - Obstructive sleep apnoea syndrome--patients' perceptions of their sleep and its
      effects on their life situation.
AB  - AIM: This paper reports a descriptive study of how untreated patients with
      obstructive sleep apnoea syndrome perceived their sleep situation and how the
      syndrome affected their life situation. BACKGROUND: Obstructive sleep apnoea
      syndrome is a prevalent problem independently associated with an increased risk
      for hypertension, cardiovascular disease, chronic heart failure and mortality.
      Increased consumption of healthcare resources can often be seen among patients
      over a long period of time since many have been undiagnosed and untreated.
      METHODS: A phenomenographic approach was employed. Data were collected by
      interviews during 2005 with 20 purposively selected participants with untreated
      obstructive sleep apnoea syndrome. Findings. Participants described loud snoring,
      frequent awakenings, dyspnoea, frustration over nocturia, fear of dying during
      sleep and partners' anxiety about the apnoea, as being night-time effects of
      obstructive sleep apnoea syndrome. They described dry and sore throats, tiredness
      and daytime sleepiness, shame about falling asleep and snoring, thoughts about
      complications and depressed mood as daytime effects. Needs, such as increased
      alertness, improved ability to concentrate, improved relationship, adequate
      information as well as effective treatment, were described. Participants tried
      self-care strategies such as information-seeking about sleep disturbances and
      treatment, adapted sleeping routines, change of bedroom arrangements, adapted
      daily schedules, hyperactivity and avoidance of difficult situations. CONCLUSION:
      The perceived effects and needs, as well as tried self-care actions by the
      patients with obstructive sleep apnoea syndrome in this study, could be used to
      identify and evaluate concerns of other patients with obstructive sleep apnoea
      syndrome waiting for treatment.

PMID- 17233652
TI  - Factors influencing the development of evidence-based practice: a research tool.
AB  - AIM: The paper reports a study to develop and test a tool for assessing a range
      of factors influencing the development of evidence-based practice among clinical
      nurses. BACKGROUND: Achieving evidence-based practice is a goal in nursing
      frequently cited by the profession and in government health policy directives.
      Assessing factors influencing the achievement of this goal, however, is complex.
      Consideration needs to be given to a range of factors, including different types
      of evidence used to inform practice, barriers to achieving evidence-based
      practice, and the skills required by nurses to implement evidence-based care.
      METHODS: Measurement scales currently available to investigate the use of
      evidence in nursing practice focus on nurses' sources of knowledge and on
      barriers to the use of research evidence. A new, wider ranging Developing
      Evidence-Based Practice questionnaire was developed and tested for its
      measurement properties in two studies. In study 1, a sample of 598 nurses working
      at two hospitals in one strategic health authority in northern England was
      surveyed. In study 2, a slightly expanded version of the questionnaire was
      employed in a survey of 689 community nurses in 12 primary care organizations in
      two strategic health authorities, one in northern England and the other in
      southern England. FINDINGS: The measurement characteristics of the new
      questionnaire were shown to be acceptable. Ten significant, and readily
      interpretable, factors were seen to underlie nurses' relation to evidence-based
      practice. CONCLUSION: Strategies to promote evidence-based practice need to take
      account of the differing needs of nurses and focus on a range of sources of
      evidence. The Developing Evidence-Based Practice questionnaire can assist in
      assessing the specific 'evidencing' tendencies of any given group of nurses.

PMID- 17233653
TI  - A concept analysis of self-monitoring.
AB  - AIM: This paper reports a concept analysis delineating and clarifying the concept
      of self-monitoring to facilitate development and evaluation of interventions to
      enhance self-monitoring. BACKGROUND: The concepts of self-monitoring, self
      management, self-care and symptom management are often used in similar or
      interchangeable ways. Clarification of the concept of self-monitoring is needed
      for research and theory development. METHOD: Rodgers and Knafl's evolutionary
      concept analysis process was used to delineate and clarify the concept. The
      PubMed and CINAHL databases were searched using keywords 'self-monitoring', 'self
      management' and 'self-care' (with and without the hyphen) for the years 1998
      2005, to update a previous study (not published). Later, searching was refined
      and the keyword 'self-monitoring' was paired with 'awareness' and 'self
      regulation' was added. Approximately half the papers were from nursing (n = 34)
      and half from other disciplines (n = 32). The sample from 1998 to 2005 was
      further stratified by chronic condition. Definition, exemplars, usage,
      attributes, antecedents/consequences and implications for further study were
      identified. FINDINGS: Self-monitoring was composed of two complementary
      components (attributes): (1) awareness of bodily symptoms, sensations, daily
      activities, and cognitive processes and (2) measurements, recordings and
      observations that inform cognition or provide information for independent action
      or consultation with care providers. CONCLUSION: Self-monitoring may be an
      important concept for understanding how people self-manage chronic conditions.
      This concept analysis may be useful for researchers who wish to measure this
      dimension and to develop nursing theory in this area.

PMID- 17233662
TI  - Avoiding unintentional plagiarism.

PMID- 17233663
TI  - Psychosocial care needs of children with recent-onset asthma.
AB  - PURPOSE: To examine psychosocial care needs of children with recent-onset asthma.
      DESIGN/METHODS: Data were collected over 2 years from 63 children ages 8-14
      years. RESULTS: Children's need for attention to specific aspects of their asthma
      care remained high over the 2 years, as did their perceived needs for information
      and support and their concerns and fears. PRACTICE IMPLICATIONS: Children have
      many needs, and healthcare professionals may not be providing care that addresses
      these needs. The Child Report of Psychosocial Care can be used as a quick tool to
      assess and guide interventions related to specific areas of need.

PMID- 17233664
TI  - Lived experiences of mothers caring for children with thalassemia major in
      Thailand.
AB  - ISSUES AND PURPOSE: Thalassemic patients must be given continuous treatment
      throughout their lives due to the physical and psychological effects of their
      disorder; their families also are impacted. This qualitative study explored the
      lived experiences of 15 mothers of children with thalassemia major by conducting
      semistructured interviews; the data were analyzed utilizing content analysis.
      CONCLUSION: Six themes were identified: lack of knowledge about thalassemia,
      psychosocial problems, concerns for the future, social support systems, financial
      difficulty, and the effectiveness of healthcare services. PRACTICE IMPLICATIONS:
      These findings suggest that a holistic, culturally sensitive nursing approach
      should be considered when caring for children with thalassemia.

PMID- 17233666
TI  - Attachment and sexual health behaviors in homeless youth.
AB  - PURPOSE: To explore relationships and group differences in attachment-related
      constructs (social connectedness and social support) and sexual health behaviors
      in a sample of homeless youth. DESIGN AND METHODS: An exploratory design, this
      study analyzed baseline data from an ongoing intervention study. Survey data were
      collected by audio, computer-assisted self-interview (A-CASI) from a
      nonprobability sample of homeless youth (n = 176). RESULTS: Social connectedness
      was positively correlated with period of time homeless, while social support was
      positively related to sexual self-concept and to self-efficacy and intention to
      use condoms. PRACTICE IMPLICATIONS: The street group that homeless youth identify
      with may be a potential resource for peer-mentoring and skill-building regarding
      healthy sexual behavior.

PMID- 17233665
TI  - Maturing responsibility in young teens participating in an asthma camp: adaptive
      mechanisms and outcomes.
AB  - PURPOSE: The purpose of this study was to describe adolescent adaptation in the
      four adaptive modes of the Roy Adaptation Model in campers attending a Young Teen
      Asthma Camp and relate that adaptation to the acquisition of asthma
      responsibility. DESIGN AND METHODS: The camp experience included asthma education
      and an opportunity to grow socially. A quasi-experimental design investigated
      ratings of self-efficacy and responsibility from before to after camp. RESULTS:
      Improvements in self-efficacy supported adaptation in self-concept and role
      function. Adolescents demonstrated maturing responsibility in asthma management
      in interdependence mode. PRACTICE IMPLICATIONS: Asthma camps are effective for
      delivering asthma education, enhancing maturation, and assisting with normalizing
      life experiences. Nurses can be instrumental in facilitating adolescents'
      participation.

PMID- 17233667
TI  - Family coping and disease control when a child has type I diabetes mellitus: a
      review of the literature.

PMID- 17233668
TI  - Transitioning adolescents with special healthcare needs: potential barriers and
      ethical conflicts.

PMID- 17233670
TI  - Integrated medical and dental health in primary care.

PMID- 17233669
TI  - Clinical statistics for primary care practitioners: part I--incidence,
      prevalence, and the odds ratio.

PMID- 17233671
TI  - Quality of care: or why you have to evaluate your program.

PMID- 17233672
TI  - Black holes, antivirulence genes, and gene inactivation in the evolution of
      bacterial pathogens.
AB  - The evolution of bacterial pathogens from nonpathogenic ancestors is marked
      principally by the acquisition of virulence gene clusters on plasmids and
      pathogenicity islands via horizontal gene transfer. The flip side of this
      evolutionary force is the equally important adaptation of the newly minted
      pathogen to its new host niche. Pathoadaptive mutations take the form of
      modification of gene expression such that the pathogen is better fit to survive
      within the new niche. This mini-review describes the concept of pathoadaptation
      by loss of gene function. In this process, genes that are no longer compatible
      with the novel lifestyle of the pathogen are selectively inactivated either by
      point mutation, insertion, or deletion. These genes are called 'antivirulence
      genes'. Selective pressure sometimes leads to the deletion of large regions of
      the genome that contain antivirulence genes generating 'black holes' in the
      pathogen genome. Inactivation of antivirulence genes leads to a pathogen that is
      highly adapted to its host niche. Identification of antivirulence genes for a
      particular pathogen can lead to a better understanding of how it became a
      pathogen and the types of genetic traits that need to be silenced in order for
      the pathogen to colonize its new host niche successfully.

PMID- 17233673
TI  - Identification of New World Leishmania species from Peru by biochemical
      techniques and multiplex PCR assay.
AB  - We have characterized diverse strains or species of Leishmania isolated in humans
      that are currently circulating throughout Peru, by means of isoenzymatic
      characterization, kDNA analysis by restriction enzymes, and multiplex PCR assay.
      The cluster analysis gave five groups. Cluster 1 includes L. (L.) donovani
      together with the isolates LP4 and LP7, forming the donovani complex. Thus, this
      complex corresponds to the New World visceral form, L. (L.) chagasi. Cluster 2 is
      formed by the isolates LP1-LP3, LP6, LP10, LP9, and LP11, phylogenetically
      intermediate between Cluster 1 and Cluster 3, or they can be treated as hybrids.
      Cluster 3 is divided into two subgroups: one formed by L. (V.) peruviana,
      together with the isolates LP14 and LP5, and the second one formed by L. (V.)
      brazilensis and the isolate LP8. These two subgroups form part of the brazilensis
      complex. The three strains of L. (L.) infantum [L. (L.) infantum I and II and la
      LSI] make up Cluster 4. In Cluster 5, we include the three Mexican strains (LM1
      LM3) forming one subgroup while we would place L. (L.) amazonensis in another
      subgroup. These two subgroups would comprise the complex mexicana.

PMID- 17233674
TI  - The Sinorhizobium meliloti ExoR protein is required for the downregulation of
      lpsS transcription and succinoglycan biosynthesis in response to divalent
      cations.
AB  - The Sinorhizobium meliloti lpsS gene encodes a sulfotransferase that modifies
      lipopolysaccharide. Mutants lacking lpsS display no defect in lipopolysaccharide
      sulfation when assayed under laboratory conditions, but exhibit an abnormal
      symbiosis with alfalfa. These results suggest that lpsS is transcriptionally
      repressed under laboratory conditions, but upregulated during symbiosis. Here, it
      is shown that lpsS, as well as exo genes required for the biosynthesis of
      succinoglycan, are transcriptionally repressed in laboratory media containing
      divalent cations. Furthermore, the divalent cation-dependent transcriptional
      downregulation of lpsS is dependent on the exoR gene, which encodes a global
      regulator of transcription.

PMID- 17233675
TI  - Effect of acidic pH on the ability of Clostridium sporogenes MD1 to take up and
      retain intracellular potassium.
AB  - At pH values >5.5, Clostridium sporogenes MD1 accumulated potassium even though
      it had little protonmotive force, but an ATPase inhibitor (N, N'-
      dicyclohexylcarbodiimide) prevented this uptake. The results suggested that
      potassium transport was ATP-driven, and a protonophore (3, 3', 4', 5 -
      tetrachlorosalicylanilide) did not eliminate uptake. However, potassium uptake
      could also be driven by an artificial pH gradient, and in this case the
      protonophore acted as an inhibitor. These latter results indicated that the cells
      also had a protonmotive force-driven transporter. When the pH <5.1, the cells
      could not retain potassium, rapid efflux was observed, and intracellular volume
      collapsed.

PMID- 17233676
TI  - The role of the omega subunit of RNA polymerase in expression of the relA gene in
      Escherichia coli.
AB  - The rpoZ gene for the omega subunit of Escherichia coli RNA polymerase
      constitutes single operon with the spoT gene, which is responsible for the
      maintenance of stringent response under nutrient starvation conditions. To
      identify the physiological role of the omega subunit, we compared the gene
      expression profile of wild-type Escherichia coli with that of an rpoZ deleted
      strain by microarray analysis using an E. coli DNA chip. Here we report on a set
      of genes which show changes in expression profile following the removal of rpoZ.
      We have seen that relA, which is responsible for the synthesis of the stringent
      factor ppGpp and many ribosomal proteins, exhibited noticeable changes in mRNA
      levels and were therefore further analyzed for their expression using a GFP/RFP
      two-fluorescent protein promoter assay vector. In the absence of rpoZ, the
      promoter for the relA gene was severely impaired, but the promoters from the
      ribosomal protein genes were not affected as much. Taking these results together
      we propose that the omega subunit is involved in regulation of the relA gene, but
      induction of the stringently controlled genes in the absence of rpoZ is, at least
      in part, attributable to a decrease in ppGpp level.

PMID- 17233677
TI  - Identification of a novel two-peptide lantibiotic, haloduracin, produced by the
      alkaliphile Bacillus halodurans C-125.
AB  - Complete genome sequencing of the alkaliphilic bacterium Bacillus halodurans C
      125 revealed the presence of several genes homologous to those involved in the
      production of lantibiotic peptides. Additional bioinformatic analysis identified
      a total of eleven genes, spanning a 15 kbp region, potentially involved in the
      production, modification, immunity and transport of a two-peptide lantibiotic.
      Having established that strain C-125 exhibited antimicrobial activity against a
      wide range of Gram-positive bacteria, it was demonstrated through peptide
      purification, MS and site-directed mutagenesis that this activity was indeed
      attributable to the production of a lantibiotic encoded by these genes. This
      antimicrobial has been designated haloduracin and represents the first occasion
      wherein production of two-peptide lantibiotic has been associated with a Bacillus
      sp. It is also the first example of a lantibiotic of any kind to be produced by
      an alkaliphilic species.

PMID- 17233679
TI  - Efficacy and feasibility of a novel tri-modal robust exercise prescription in a
      retirement community: a randomized, controlled trial.
AB  - OBJECTIVES: To test the feasibility and efficacy of current guidelines for
      multimodal exercise programs in older adults. DESIGN: Randomized, controlled
      trial. SETTING: Retirement village. PARTICIPANTS: Thirty-eight subjects (14 men
      and 24 women) aged 76.6 +/- 6.1. INTERVENTION: A wait list control or 10 weeks of
      supervised exercise consisting of high-intensity (80% of one-repetition maximum
      (1RM)) progressive resistance training (PRT) 3 days per week, moderate-intensity
      (rating of perceived exertion 11 to 14/20) aerobic training 2 days per week, and
      progressive balance training 1 day per week. MEASUREMENTS: Blinded assessments of
      dynamic muscle strength (1RM), balance, 6-minute walk, gait velocity, chair
      stand, stair climb, depressive symptoms, self-efficacy, and habitual physical
      activity level. RESULTS: Higher baseline strength and psychological well-being
      were associated with better functional performance. Strength gains over 10 weeks
      averaged 39+/-31% in exercise, versus 21+/-24% in controls (P=.10), with greater
      improvements in hip flexion (P=.01), hip abduction (P=.02), and chest press
      (P=.04) in the exercise group. Strength adaptations were greatest in exercises in
      which the intended continuous progressive overload was achieved. Stair climb
      power (12.3+/-15%, P=.002) and chair stand time (-7.1+/-15%, P=.006) improved
      significantly and similarly in both groups. Reduction in depressive symptoms was
      significantly related to compliance (attendance rate r=-0.568, P=.009, PRT
      progression in loading r=-0.587, P=.02, and total volume of aerobic training r=
      0.541, P=.01), as well as improvements in muscle strength (r=-0.498, P=.002).
      CONCLUSION: Robust physical and psychological adaptations to exercise are linked,
      although volumes and intensities of multiple exercise modalities sufficient to
      cause significant adaptation appear difficult to prescribe and adhere to
      simultaneously in older adults.

PMID- 17233680
TI  - Change in motor function and risk of mortality in older persons.
AB  - OBJECTIVES: To assess the association between change in motor function and
      mortality. DESIGN: Prospective, observational cohort study. SETTING:
      Approximately 40 retirement communities across the Chicago metropolitan area
      participating in the Rush Memory and Aging Project. PARTICIPANTS: Eight hundred
      thirty-seven community-based older persons without dementia. MEASUREMENTS: Change
      in composite measures of motor performance and muscle strength. RESULTS: During a
      mean follow-up of 2.2 years, 81 persons died. In a proportional hazards model
      adjusted for age, sex, education, and body mass index, each 1-unit increase in
      the level of baseline motor performance was associated with an approximately 10%
      decrease in risk of mortality (hazard ratio (HR)=0.901, 95% confidence interval
      (CI)=0.863-0.941), and each unit of annual increase in motor performance was
      associated with an approximately 11% decrease in the risk of mortality (HR=0.887,
      95% CI=0.835-0.942). In a similar model, each 1-unit increase in the level of
      baseline strength was associated with an approximately 9% decrease in the risk of
      mortality (HR=0.906, 95% CI=0.859-0.957), and each 1-unit annual increase in
      strength was associated with an approximately 10% decrease in the risk of
      mortality (HR=0.898, 95% CI=0.809-0.996). These results were similar when men and
      women were analyzed separately and after controlling for physical activity,
      cognition, and chronic disorders. When motor performance and muscle strength were
      examined in a single model, only baseline and annual change in motor performance
      were associated with mortality. CONCLUSION: Level and rate of change in strength
      and motor performance are associated with mortality. The attenuation of the
      association between strength and mortality by motor performance suggests that
      motor function is not a unitary process and that its components may vary in their
      associations with adverse health consequences in older persons.

PMID- 17233682
TI  - Risk factors for adverse drug events in older adults with mobility limitations in
      the community setting.
AB  - OBJECTIVES: To investigate risk factors for self-reported adverse drug events
      (ADEs) in a cohort of annually surveyed Iowa Medicare beneficiaries with mobility
      limitations. DESIGN: Prospective cohort study with baseline and two annual follow
      up questionnaires. SETTING: Population-based sample of Iowa Medicare
      beneficiaries with mobility limitations. PARTICIPANTS: Members of the cohort with
      complete follow-up questionnaires and prescription dispensing data (N=689).
      MEASUREMENTS: The questionnaires asked about self-reported ADEs in the previous
      12 months, sociodemographic data, smoking, alcohol use, number of mobility
      limitations, and history of chronic disease. Pharmacy dispensing records were the
      source of number and classes of prescription drug use. Linked Medicare claims
      provided additional comorbidity data. RESULTS: Of the 689 subjects, 151 (21.9%)
      reported an ADE, 83% of which resulted in physician contact and 56% of which
      resulted in discontinuing the medication. Number of different medications
      dispensed during the prior year was an independent predictor of a self-reported
      ADE. Neither age, extent of mobility limitation, nor number of chronic conditions
      was independently associated with reporting an ADE. CONCLUSION: Excess ADE risk
      observed with increasing mobility limitations is mediated through greater
      medication use.

PMID- 17233681
TI  - Effects of muscle strength training and megestrol acetate on strength, muscle
      mass, and function in frail older people.
AB  - OBJECTIVES: To determine the independent and combined effects of progressive
      resistance muscle strength training (PRMST) and megestrol acetate (MA) on
      strength, muscle mass, and function in older recuperative care patients. DESIGN:
      Double-blind, randomized, controlled intervention using a two-by-two factorial
      design and conducted between 1999 and 2001. SETTING: University-affiliated
      Department of Veterans Affairs hospital. PARTICIPANTS: Twenty-nine patients (mean
      age 79.4 +/- 7.4, 90% white) aged 65 and older and had recent functional decline.
      INTERVENTIONS: After randomization to one of four treatment groups (low
      resistance exercises plus 800 mg per day of MA or a placebo or high-intensity
      PRMST plus 800 mg/d of MA or placebo), subjects received training and the drug or
      placebo for 12 weeks. MEASUREMENTS: Change in muscle strength, mid-thigh muscle
      area, and aggregate functional performance score as assessed using analysis of
      covariance. RESULTS: Five subjects withdrew from the study before its completion.
      Based on intent-to-treat analyses, subjects who received high-intensity PRMST and
      placebo experienced the greatest strength gains. The addition of MA was
      associated with worse outcomes than with high-intensity exercise training alone,
      especially with regard to the leg exercises. Post hoc analysis demonstrated that
      subjects who received high-intensity PRMST and placebo experienced significantly
      greater percentage increases in leg strength than subjects in either of the MA
      treatment groups (P<.05 for each comparison). There was also a significant
      negative effect of MA on physical function. In general, subjects who received MA
      experienced a deterioration in aggregate physical function scores, whereas the
      remaining subjects improved (-0.80+/-0.40 vs 0.48+/-0.41, P=.04). There was not a
      significant interaction between exercise and MA for any outcome. CONCLUSION: High
      intensity PRMST is a safe and well-tolerated exercise regimen for frail elderly
      patients. The addition of MA appears to blunt the beneficial effects of PRMST,
      resulting in less muscle strength and functional performance gains.

PMID- 17233683
TI  - Effect of multivitamin and mineral supplementation on episodes of infection in
      nursing home residents: a randomized, placebo-controlled study.
AB  - OBJECTIVES: To evaluate the effect of vitamin and mineral supplementation on
      infections in an elderly institutionalized population. DESIGN: Eighteen-month,
      randomized, placebo-controlled trial. SETTING: Twenty-one long-term care
      facilities. PARTICIPANTS: Seven hundred sixty-three subjects from 21 long-term
      care facilities. INTERVENTION: Participants were randomized to receive one
      multivitamin and mineral supplementation daily or placebo. MEASUREMENTS: The
      primary outcome was number of infections per subject. Secondary outcomes were
      antibiotic use and hospitalization rates. Infection control surveillance was
      conducted over 18 months using standardized criteria. RESULTS: Outcome data from
      748 subjects, mean age 85, were included in the intention-to-treat analysis.
      Using univariate analyses, there was no difference in infectious episodes between
      the supplemented and placebo groups (3.5 infections per 1,000 resident-days vs
      3.8 infections per 1,000 resident-days, odds ratio (OR)=0.92, 95% confidence
      interval (CI)=0.82-1.03, P=.12). There was a reduction in antibiotic usage in the
      supplementation group, but this was not significant in the multivariate model.
      There was no difference in the number of hospital visits. In the multivariate
      analysis, the effect of multivitamin use on total number of infections was not
      significant (OR=0.77, 95% CI=0.54-1.1). Subjects without dementia had a greater
      rate of infections than those with dementia (OR=1.44, 95% CI=1.19-1.76). In post
      hoc subgroup analysis, subjects without dementia who received supplementation had
      a significantly lower rate of infections than those who received placebo
      (relative risk=0.81, 95% CI=0.66-0.99). CONCLUSION: Overall, multivitamin and
      mineral supplementation does not have a significant effect on the incidence of
      infections in institutionalized seniors, although the subgroup of residents in
      long-term care without dementia may benefit from supplementation. Further
      research is needed to determine its effect in high-risk subgroups within the
      nursing home population.

PMID- 17233684
TI  - Use of a computer-based reminder to improve sedative-hypnotic prescribing in
      older hospitalized patients.
AB  - OBJECTIVES: To develop a feasible, inexpensive, point-of-care computerized
      reminder to improve sedative-hypnotic prescribing in hospitalized older people.
      DESIGN: Pre-postintervention with a computer-based reminder. SETTING: Academic
      medical center. PARTICIPANTS: Hospitalized patients aged 65 and older.
      INTERVENTION: Computer-based reminder directing clinicians to prescribe a
      nonpharmacological sleep protocol, to minimize the potential for harm with
      diphenhydramine and diazepam use by choosing an alternative medication (trazodone
      or lorazepam), or both. MEASUREMENTS: Frequency of prescription of four sedative
      hypnotic drugs (diphenhydramine, diazepam, lorazepam, and trazodone) during the
      12 months before (n=12,356 patients) and after (n=12,153) the reminder was
      instituted. RESULTS: Prescribing of sedative-hypnotics decreased from 2,208 per
      12,356 (18%) patients preintervention to 1,832 per 12,153 (15%) postintervention
      (odds ratio for the intervention=0.82, 95% confidence interval=0.76-0.87), an 18%
      risk reduction. Combined prescription rates for all four drugs fell consistently
      throughout the postintervention period. Diphenhydramine, diazepam, and lorazepam
      orders declined overall, with lorazepam prescriptions decreasing 39% during the
      intervention. Ninety-five percent of patients were successfully directed to a
      safer sedative-hypnotic drug or a nonpharmacological sleep protocol. CONCLUSION:
      Using real-time computer-based reminders could lead to improved sedative-hypnotic
      prescribing for older persons in acute care. This study highlights the potential
      to address patient safety concerns, and the quality of medication prescribing in
      particular, in vulnerable hospitalized patients.

PMID- 17233685
TI  - What level of alcohol consumption is hazardous for older people? Functioning and
      mortality in U.S. and English national cohorts.
AB  - OBJECTIVES: To estimate disability plus mortality risks in older people according
      to level of alcohol intake. DESIGN: Two population-based cohort studies. SETTING:
      The Health and Retirement Study (United States) and the English Longitudinal
      Study of Aging (England). PARTICIPANTS: Thirteen thousand three hundred thirty
      three individuals aged 65 and older followed for 4 to 5 years. MEASUREMENTS:
      Difficulties with activities of daily living (ADLs), instrumental activities of
      daily living (IADLs), poor cognitive function, and mortality. RESULTS: One-tenth
      (10.8%) of U.S. men, 28.6% of English men, 2.9% of U.S. women, and 10.3% of
      English women drank more than the U.S. National Institute on Alcohol Abuse and
      Alcoholism recommended limit for people aged 65 and older. Odds ratios (ORs) of
      disability, or disability plus mortality, in subjects drinking an average of more
      than one to two drinks per day were similar to ORs in subjects drinking an
      average of more than none to one drink per day. For example, those drinking more
      than one to two drinks per day at baseline had an OR of 1.0 (95% confidence
      interval (CI)=0.8-1.2) for ADL problems, 0.7 (95% CI=0.6-1.0) for IADL problems,
      and 0.8 (95% CI=0.6-1.1) for poor cognitive function. Findings were robust across
      alternative models. The shape of the relationship between alcohol consumption and
      risk of disability was similar in men and women. CONCLUSION: Functioning and
      mortality outcomes in older people with alcohol intakes above U.S. recommended
      levels for the old but within recommendations for younger adults are not poor.
      More empirical evidence of net benefit is needed to support screening and
      intervention efforts in community-living older people with no specific
      contraindications who drink more than one to two drinks per day.

PMID- 17233687
TI  - Effect of cancer screening and desirable health behaviors on functional status,
      self-rated health, health service use and mortality.
AB  - OBJECTIVES: To determine whether some health behaviors of older people (e.g.,
      obtaining cancer screens) have a limited and others (e.g., exercise) have a broad
      association with population-level health status 4 to 6 years later. DESIGN:
      Longitudinal cohort. SETTING: North Carolina five-county urban and rural area.
      PARTICIPANTS: Representative community residents aged 71 and older (Duke
      Established Populations for Epidemiologic Studies of the Elderly; African
      American, n=1,256; white, n=974) who provided information on cancer screening and
      health behaviors. MEASUREMENTS: Demographics, health conditions, functional
      status, health service use, health insurance. Dependent measures were functional
      status and self-rated health 4 years later, hospitalization within 4 years, and
      death within 6 years. Data were analyzed using descriptive statistics,
      multivariable logistic regression, and Cox proportional hazards. RESULTS: In
      fully adjusted analyses, cancer screening had no significant protective
      association with functional status, self-rated health, hospitalization, or death.
      Smoking was a risk factor for hospitalization (odds ratio (OR)=1.48, 95%
      confidence interval (CI)=1.07-2.05), and death (hazard rate (HR)=1.81, 95%
      CI=1.47-2.23). Sufficient food reduced hospitalization (OR=0.38, 95% CI=0.15
      0.94) and mortality (HR=0.70, 95% CI=0.49-1.02). Regular exercise protected
      against poor mobility (OR=0.56, 95% CI=0.41-0.77), and poor self-rated health
      (OR=0.61, 95% CI=0.45-0.82). Lower activity level increased the hazard of death
      (HR=1.18, 95% CI=1.03-1.36). CONCLUSION: Disease-specific screens are important
      at an individual level but, because of low incidence of condition and
      comorbidity, may not be associated with population-level health 4 to 6 years
      later. Practice of health behaviors with a broader focus is associated, at a
      population level, with better functional status and self-rated health and lower
      rates of hospitalization and death 4 to 6 years later.

PMID- 17233686
TI  - Age-associated declines in complex walking task performance: the Walking
      InCHIANTI toolkit.
AB  - OBJECTIVES: To describe a set of complex walking tasks (CWTs) that can be used to
      evaluate mobility and to characterize age- and sex-specific performance on these
      tests. DESIGN: A population-based study of persons living in the Chianti
      geographic area (Tuscany, Italy). SETTING: Community. PARTICIPANTS: One thousand
      two hundred twenty-seven persons (aged 20-95) selected from the city registries
      of Greve and Bagno a Ripoli (Tuscany, Italy). MEASUREMENTS: Gait velocity (m/s)
      was measured during 13 walking tests (Walking InCHIANTI Toolkit (WIT)) used to
      examine walking ability under a range of conditions and distances. Other measures
      included performance on the Short Physical Performance Battery and self-reported
      health and functional status, including disability in activities of daily living.
      RESULTS: Age-associated differences on the WIT were reflected in the number of
      older adults unable to complete CWTs and a decrease in gait velocity. For all
      tasks, decrements in walking speed with increasing age were significantly larger
      at aged 65 and older. Performance on CWTs was highly variable and could not be
      explained by usual gait speed measured under low-challenge conditions alone.
      CONCLUSION: CWTs may provide important insight into mobility function,
      particularly in persons with normal or near-normal usual gait speed. Further
      research is needed to elucidate the specific physiological mechanisms that
      contribute to declining performance on CWT with increasing age.

PMID- 17233688
TI  - Treatment and prevention of depression after surgery for hip fracture in older
      people: randomized, controlled trials.
AB  - OBJECTIVES: To evaluate the effect of a psychiatric intervention in treating
      depression (treatment study) and the effect of a psychological treatment in
      preventing depression (prevention study) after hip fracture in older people.
      DESIGN: Two linked randomized, controlled trials. SETTING: Orthopedic units in
      Manchester, England. PARTICIPANTS: Two hundred ninety-three older people who had
      undergone surgery for a fractured hip: 121 in the treatment study and 172 in the
      prevention study. MEASUREMENTS: The Geriatric Depression Scale and Hospital
      Anxiety and Depression Scale for mood, functional tests for mobility and pain
      measures. RESULTS: There was a slight reduction in depressive symptoms in the
      active arm of the treatment study. In the prevention study, there was no
      significant difference in incident depression between the psychological
      intervention and treatment as usual. There were no differences in the functional
      and pain outcomes. CONCLUSION: The results from these two randomized, controlled
      trials show that, after hip fracture surgery, no statistically significant
      benefits can be achieved from a psychiatric intervention in people who are
      depressed or a psychological intervention to prevent the onset of depression.

PMID- 17233689
TI  - Onset of depression in elderly persons after hip fracture: implications for
      prevention and early intervention of late-life depression.
AB  - OBJECTIVES: To identify predictors of onset of major depressive disorder (MDD)
      and of depressive symptoms in subjects who suffered a hip fracture. DESIGN:
      Prospective naturalistic study. SETTING: University of Pittsburgh Medical Center
      Shadyside, a large urban hospital in Pittsburgh, Pennsylvannia. PARTICIPANTS: One
      hundred twenty-six elderly patients who received surgical fixation for hip
      fracture and who were not experiencing a major depressive episode at the time of
      the fracture; severely cognitively impaired persons were excluded. MEASUREMENTS:
      Subjects were evaluated at the time of hospital discharge using a battery of
      clinical measures (including apathy measured using the Apathy Evaluation Scale
      (AES), delirium, cognitive measures, social support, and disability level).
      Depression was assessed at the end of the surgical stay, 2 weeks later, and then
      monthly for 6 months, using the Hamilton Rating Scale for Depression (Ham-D) to
      evaluate symptomatology and the Primary Care Evaluation of Mental Disorders to
      evaluate diagnosis of MDD. RESULTS: Eighteen of 126 subjects (14.3%) developed
      MDD after hip fracture. Of these, 11 developed MDD by the end of the
      hospitalization, and seven developed MDD between 2 and 10 weeks later. Logistic
      regression showed that baseline apathy score, as measured using the AES, was the
      only clinical measure associated with the development of MDD (odds ratio=1.09,
      95% confidence interval=1.03-1.16, P=.003); 46.2% of those with high AES scores
      developed MDD, versus 10.9% of those with lower scores. In contrast, cognitive
      variables, delirium, disability after hip fracture, and other factors related to
      the fracture (e.g., fracture type) were not associated with MDD. A repeated
      measures analysis with Ham-D over time as a dependent variable generally
      confirmed these findings; depressive symptoms were highest immediately after the
      fracture, and apathy and delirium scores were associated with higher depressive
      symptom levels. CONCLUSION: The onset of MDD is common after hip fracture, and
      the greatest period of risk is immediately after the fracture. Individuals with
      clinical evidence of apathy are at high risk for developing MDD, and evaluation
      and close follow-up of such individuals is warranted. However, further research
      is needed to examine other candidate variables (e.g., clinical measures or
      biomarkers) to model adequately the risk for MDD after hip fracture and other
      disabling medical events.

PMID- 17233690
TI  - Aging and the prevalence of cardiovascular disease risk factors in older American
      Indians: the Strong Heart Study.
AB  - OBJECTIVES: To describe longitudinal changes in the prevalence of major
      cardiovascular disease (CVD) risk factors in aging American Indians. DESIGN:
      Population-based ongoing epidemiological study. SETTING: The Strong Heart Study
      is a study of CVD and its risk factors. Standardized examinations were repeated
      in 1993 to 1995 and again in 1997 to 1999. PARTICIPANTS: A diverse cohort of
      4,549 American Indians aged 45 to 74 at the initial examinations in 1989 to 1991.
      MEASUREMENTS: Changes in the prevalence of hypertension, low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), current
      smoking, and type 2 diabetes mellitus. RESULTS: The prevalence of hypertension
      rose rapidly and steadily with aging. A nonsignificant decrease in LDL-C was seen
      in men, and men and women initially had rapid increases in the prevalence of low
      HDL-C. The prevalence of smoking decreased, but the prevalence of diabetes
      mellitus continued to rise for men and women. CONCLUSION: Overall, unfavorable
      changes in CVD risk factors were seen in the aging participants and will likely
      be reflected in worsening morbidity and mortality.

PMID- 17233691
TI  - The Japanese Centenarian Study: autonomy was associated with health practices as
      well as physical status.
AB  - OBJECTIVES: To investigate the prevalence of centenarians who have preserved
      activities of daily living (ADLs) and good cognitive and psychosocial status in
      Japan. DESIGN: Census-based survey. SETTING: Cross-Sectional Investigation of
      Half of All Japanese Centenarians Study, 2000. PARTICIPANTS: A nationwide census
      based study was conducted of all of the male centenarians and a random sample of
      half of all the female centenarians who were included in the National Census of
      Japan. After excluding those who had died and whose addresses could not be
      identified, 1,907 centenarians (53.0%) participated in the present visitation
      interview survey. MEASUREMENTS: ADLs, cognitive status, and psychosocial status.
      Centenarians who have preserved ADLs and good cognitive and psychosocial status
      were defined as autonomous centenarians. RESULTS: Of the study subjects, 10.4%
      were judged to be autonomous centenarians. Multiple logistic regression analyses
      revealed that autonomy in centenarians was associated with better visual acuity,
      getting regular exercise, spontaneous awakening regularly in the morning,
      preserved masticatory ability, having no history of drinking, having no history
      of severe falls after the age of 95, more frequent intake of protein, living at
      home, and being male. It was also demonstrated that autonomous centenarians were
      not associated with appetite, vegetable or seaweed intake, smoking habits,
      auditory capacity, body mass index, or present illness. CONCLUSION: These
      findings suggest that health practices play an important role in preserving ADLs
      and good cognitive and psychosocial status after reaching the age of 100 and
      should be useful for establishing an educational program for the ever-increasing
      "super elderly" population in Japan.

PMID- 17233692
TI  - Medication costs: the role physicians play with their senior patients.
AB  - OBJECTIVES: To determine how often primary care physicians discuss medication
      costs with their senior patients and what cost-reducing strategies they employ.
      DESIGN: Cross-sectional, random-sample mail questionnaire. SETTING: State of
      California. PARTICIPANTS: Six hundred seventy-eight of 1,098 (62%) internal
      medicine and family practice physicians selected from the American Medical
      Association Masterfile. MEASUREMENTS: Main outcomes included frequency of cost
      discussions with senior patients in the previous 30 days and choice of cost
      reducing strategy when a senior expresses financial difficulty with medication
      costs. RESULTS: Forty-three percent of physicians reported discussing medication
      cost with at least half of their senior patients in the previous 30 days.
      Patients initiated most of these discussions. Forty percent reported that, at
      least one time in the previous 30 days, they had not discussed cost but wished
      they had. The most common reason given was "I ran out of time" (36%). Physicians
      with high perceived knowledge of medication costs were more likely to discuss
      cost (odds ratio (OR)=3.49, 95% confidence interval (CI)=1.66-7.3) versus low
      perceived knowledge, but this trend was not seen in physicians who scored high on
      actual knowledge of medication costs (OR=0.78, 95% CI=0.43-1.43) versus low
      actual knowledge. The most common cost-reducing strategies were generic
      substitution (33%) and offering samples (25%). CONCLUSION: The frequency of
      medication cost discussions between physicians and senior patients is low, and
      when it occurs, is often initiated by patients. Physicians' perception of their
      knowledge of medication costs may be an important factor in initiating cost
      discussions.

PMID- 17233693
TI  - The association between serum folate levels and periodontal disease in older
      adults: data from the National Health and Nutrition Examination Survey 2001/02.
AB  - OBJECTIVES: To assess the relationship between serum folate levels and
      periodontal disease in older adults. DESIGN: Population-based cross-sectional
      study. SETTING: National Health and Nutritional Examination Survey 2001/02.
      PARTICIPANTS: Eight hundred forty-four dentate elderly subjects aged 60 and older
      (mean age 70.6) who completed a periodontal examination and laboratory test for
      serum folate levels. MEASUREMENTS: Periodontal examination, including probing
      depth and attachment loss, was performed. Periodontal disease was defined as
      having at least 10% of sites with clinical attachment loss of more than 4 mm and
      at least 10% sites with probing depth of more than 3 mm. Serum folate levels were
      measured using a commercially available radioprotein binding assay kit. RESULTS:
      After controlling for demographics, educational level, body mass index, bleeding
      on probing, and probing sites, the odds ratio for periodontal disease was 0.74
      (95% confidence interval=0.59-0.93) for each standard deviation increase in
      natural-log-transformed folate levels. After additionally controlling for levels
      of vitamin B(12) and homocysteine, chronic diseases (hypertension, diabetes
      mellitus, heart disease, and stroke), and health behaviors (smoking status and
      alcohol consumption), the negative association between folate level and
      periodontal disease remained statistically significant and essentially unchanged.
      There was no effect modification of sex on the association between serum folate
      levels and periodontal disease. CONCLUSION: A low serum folate level was
      independently associated with periodontal disease in older adults. The results
      suggest that serum folate levels, important indicators of periodontal disease in
      older adults, may provide an important clinical target for intervention to
      promote oral health.

PMID- 17233694
TI  - Community-acquired legionella pneumonia in elderly patients: characteristics and
      outcome.
AB  - OBJECTIVES: To compare the risk factors, clinical and laboratory features, and
      outcome of community-acquired pneumonia (CAP) caused by Legionella pneumophila in
      elderly (aged > or =65) and younger patients. DESIGN: Prospective enrollment of
      subjects with retrospective data analysis. SETTING: A 630-bed tertiary center in
      Badalona (Barcelona), Spain. PARTICIPANTS: A total of 158 patients diagnosed with
      CAP caused by L. pneumophila from 1994 to 2004: 104 younger than 65 and 54 aged
      65 and older. MEASUREMENTS: Epidemiological, clinical, laboratory, and
      radiological data and the outcome of the two groups were compared using
      univariate and multivariate analysis. RESULTS: Underlying diseases, such as
      chronic pulmonary diseases, diabetes mellitus, neuromuscular diseases, and heart
      failure; risk of aspiration; and therapy with corticosteroids were significantly
      more frequent in patients aged 65 and older. Patients younger than 65 were more
      likely to be male and have toxic habits (cigarette smoking, alcoholism) and human
      immunodeficiency virus infection than older patients. Fever, nonrespiratory
      symptoms (diarrhea and headache), and some laboratory abnormalities (hyponatremia
      (serum sodium concentration <130 mmol/L) and high aspartate aminotransferase and
      creatinine kinase levels) were significantly less frequent in patients aged 65
      and older than in younger patients. No significant differences were observed
      between the two groups in the frequency of higher-severity risk classes and
      intensive care unit admission or in outcome (complications and mortality).
      CONCLUSION: Elderly patients with CAP caused by L. pneumophila had a higher
      frequency of underlying comorbidities and presented less frequently with fever
      and classical nonrespiratory symptoms and laboratory abnormalities of
      Legionnaires' disease than younger patients, although greater severity of illness
      at onset and higher mortality were not significantly different between the two
      age groups.

PMID- 17233695
TI  - Using step activity monitoring to characterize ambulatory activity in community
      dwelling older adults.
AB  - OBJECTIVES: To explore the potential of using step activity monitoring to detect
      differences in ambulatory activity associated with advancing age and declining
      function in community-dwelling seniors. DESIGN: Cross-sectional pilot study.
      SETTING: General communities of Seattle, Washington; Catonsville, Maryland; and
      Durham, North Carolina. PARTICIPANTS: Thirty healthy younger adults, 28 healthy
      older adults, and 12 older adults reporting functional limitations. MEASUREMENTS:
      Ambulatory activity data were collected over 6 days with the StepWatch 3. Average
      daily values were calculated for number of steps, number of minutes of activity,
      number of activity bouts, variability of minute-to-minute activity, and
      randomness of minute-to-minute activity fluctuations. RESULTS: Healthy older
      adults engaged in fewer bouts of activity (P=.03) and displayed less-variable
      activity (P=.02) than younger adults. Older adults reporting functional
      limitations not only engaged in fewer bouts of activity (P=.009) and less
      variable activity (P<.001) than younger adults, but also accumulated fewer total
      steps (P=.003) and minutes of activity (P=.008) and had less-random minute-to
      minute activity fluctuations (P=.02). CONCLUSION: Step activity monitoring data
      were useful for detecting differences in ambulatory activity according to age and
      functional limitation. Monitor-based measures reflecting patterns of ambulatory
      activity show promise for use in studies of physical functioning.

PMID- 17233698
TI  - An Alzheimer's outlaw.

PMID- 17233697
TI  - Depression after hip fracture.

PMID- 17233699
TI  - Striving to meet divergent needs.

PMID- 17233700
TI  - Metabolic syndrome and prediction of mobility decline in older persons.

PMID- 17233702
TI  - The undergraduate curriculum "medicine in old age and the old person":
      experiences in teaching medical students at the University of Hamburg, Germany.

PMID- 17233703
TI  - Viral infection and cognitive decline.

PMID- 17233704
TI  - Total cholesterol levels and the risk of mild cognitive impairment and
      Alzheimer's disease.

PMID- 17233705
TI  - Posttraumatic subgaleal hematoma with orbital extension associated with
      clopidogrel usage in an elderly patient: case report.

PMID- 17233706
TI  - The oldest old with hypertension: treat or not treat?

PMID- 17233708
TI  - Trends in home diagnostic testing for medicare beneficiaries.

PMID- 17233709
TI  - Corrections to the report of San Mateo County enterohemorrhagic Escherichia coli
      O157:h7 outbreak associated with raw spinach.

PMID- 17233710
TI  - Mosapride citrate prolongs survival in stroke patients with gastrostomy.

PMID- 17233712
TI  - Visual hallucinations in an elderly woman: was it really Charles Bonnet syndrome?

PMID- 17233713
TI  - Effect of a 5-year multidisciplinary collaborative program on antibiotic
      consumption in an acute geriatric ward.

PMID- 17233715
TI  - Detection of quorum-sensing N-acyl homoserine lactone signal molecules by
      bacterial biosensors.
AB  - Many Gram-negative bacteria use N-acyl homoserine lactones (AHLs) as quorum
      sensing (QS) signal molecules. AHL QS has been the subject of extensive
      investigation in the last decade and has become a paradigm for bacterial
      intercellular signaling. Research in AHL QS has been considerably aided by simple
      methods devised to detect AHLs using bacterial biosensors that phenotypically
      respond when exposed to exogenous AHLs. This article reviews and discusses the
      currently available bacterial biosensors which can be used in detecting and
      studying the different AHLs.

PMID- 17233716
TI  - Molecular characterization of ICEVchVie0 and its disappearance in Vibrio cholerae
      O1 strains isolated in 2003 in Vietnam.
AB  - We analyzed 28 epidemic Vibrio cholerae O1 strains isolated in the region of Thua
      Thien Hue (Vietnam) in 2003. Ubiquitous amoxicillin, prevalent aminoglycosides
      and sporadic erythromycin resistances were observed. All were devoid of plasmids,
      class 1 integrons and ICEs and showed the same BglI ribotype, irrespective of
      their site of isolation and resistance pattern. A strain isolated in 1990 in the
      same area was resistant to amoxicillin and aminoglycosides but characterized by a
      different ribotype. This strain contained ICEVchVie0, belonging to the SXT/R391
      ICE family, devoid of any resistance cluster. The molecular analysis of three
      conserved and six variable regions outlined an original genetic profile. ICEs not
      coding for resistance to drugs seem to be more frequent than supposed, and this
      finding reinforces the idea that the SXT/R391 family of genetic elements is wide
      and composite. The clearance of ICEVchVie0 in the 2003 epidemic may be explained
      by the lack of any resistance determinant as a favorable selective marker.

PMID- 17233717
TI  - Functional identification of p-cumate operons in the terpene-degrading
      Rhodococcus sp. strain T104.
AB  - We identified a p-cumate degrading gene cluster (designated cmt) with a novel
      organization in our genomic studies of the terpene-degrading Rhodococcus sp.
      strain T104. The mutant strain SN140, isolated for the inability to grow on p
      cumate, accumulates 2,3-dihydroxy-p-cumate as identified by liquid chromatography
      mass spectrometry and 300 MHz proton nuclear magnetic resonance spectroscopy.
      Reverse transcriptase polymerase chain reaction experiments showed that the cmt
      genes are operonic and induced specifically by growth on p-cumate. This report is
      the first example of identifying the genes for p-cumate degradation in a gram
      positive organism based on functional data.

PMID- 17233718
TI  - Microscopical investigation of poly(3-hydroxybutyrate) granule formation in
      Azotobacter vinelandii.
AB  - Poly(3-hydroxybutyrate) (PHB) granule formation in Azotobacter vinelandii was
      investigated by laser scanning fluorescence microscopy after staining the cells
      with Nilered and Baclight. Cells that had been starved for a carbon source for >
      or =3 days were almost free of PHB granules. Formation of visible PHB granules
      started within 1-2 h after transfer of the cells to a medium permissive for PHB
      accumulation. Fluorescent PHB granules at the early stages of formation were
      exclusively found in the cell periphery of the 2-3 mum ovoid-shaped cells. After
      3 h of PHB accumulation or later, PHB granules were also found to be detached
      from the cell periphery. Our results indicate that PHB granule formation
      apparently begins at the inner site of the cytoplasmic membrane. This finding is
      different from previous assumptions that PHB granule formation occurs randomly in
      the cytoplasm of PHB-accumulating bacteria.

PMID- 17233719
TI  - First description of nonmotile Vibrio vulnificus strains virulent for eels.
AB  - Nonmotile Vibrio vulnificus strains were isolated as pure cultures from body
      ulcers and internal organs of wild diseased European eels caught in a
      Mediterranean freshwater coastal lagoon. All 54 V. vulnificus isolates were
      nonmotile, indole-, ornithine decarboxilase-, mannitol- and cellobiose-positive,
      developed the opaque variant in culture, belonged to the O-antigenic serovar A
      and were highly virulent for eels by both intraperitoneal injection and immersion
      challenges. The nonmotile phenotype found in our V. vulnificus isolates was
      stable: nonmotile cells were always recovered from experimentally infected eels;
      no variation in the immobility of the V. vulnificus cells was observed for
      repeated subculture by daily passages on solid media, at different temperatures
      or incubation times and with or without magnesium sulfate. Many of the fla genes
      of Vibrio were present in the genome of the nonmotile strains (flaCDE and flaFBA
      for flagellins and flaH for the distal capping protein), although we observed by
      transmission electron microscopy that these V. vulnificus strains always lacked
      the polar flagellum. This is the first report on the existence of nonmotile wild
      type V. vulnificus strains.

PMID- 17233720
TI  - Identification of the glycosyl transferase required for synthesis of the
      principal glycolipid characteristic of heterocysts of Anabaena sp. strain PCC
      7120.
AB  - Nitrogenase is oxygen-labile. Cyanobacterial heterocysts can fix N(2) in an oxic
      milieu because their interior is micro-oxic, for which the glycolipid layer of
      the heterocyst envelope is required. ORF all5341 of the Anabaena sp. genome
      predicts a glycosyl transferase. An insertional mutant of all5341 synthesized
      only a nonglycosylated form of heterocyst envelope glycolipid, and lacked a
      glycolipid layer. All5341 appears to be the transferase required to glycosylate
      the glycolipid aglycone.

PMID- 17233721
TI  - Characterization of the BLR1 gene encoding a putative blue-light regulator in the
      phytopathogenic fungus Bipolaris oryzae.
AB  - Bipolaris oryzae is a filamentous ascomycetous fungus that causes brown leaf spot
      disease in rice. We isolated and characterized BLR1, a gene that encodes a
      putative blue-light regulator similar to Neurospora crassa white-collar 1 (WC-1).
      The deduced amino acid sequence of BLR1 showed high degrees of similarity to
      other fungal blue-light regulator protein. Disruption of the BLR1 gene
      demonstrated that this gene is essential for conidial development after
      conidiophore formation and for near-UV radiation-enhanced photolyase gene
      expression.

PMID- 17233722
TI  - The growth advantage in stationary-phase (GASP) phenomenon in mixed cultures of
      enterobacteria.
AB  - Growth advantage in stationary phase (GASP) is the term used to describe the
      ability of mutants with an increased fitness from 10-day-old enterobacteria
      culture to out-compete 1-day-old cells of the same initial strain during a
      prolonged stationary phase, although the aged cells are introduced as a minority.
      We studied this bacterial trait in mixed cultures of two enterobacterial species,
      Escherichia coli and Salmonella enterica, wild type in addition to derived
      mutants from both strains that contain chromosomal-encoded resistance to either
      nalidixic acid or streptomycin. The strong GASP phenotype was obtained in mixed
      cultures with the aged mutant strains, but not when the isogenic antibiotic
      sensitive strains were used. This phenomenon was associated with chromosomal
      rearrangements in 10-day-old bacterial antibiotic-resistant mutated cells.

PMID- 17233723
TI  - Adaptation of the psychrotroph Arthrobacter chlorophenolicus A6 to growth
      temperature and the presence of phenols by changes in the anteiso/iso ratio of
      branched fatty acids.
AB  - Arthrobacter chlorophenolicus is a previously described Gram-positive bacterium
      capable of degrading high concentrations of several phenolic compounds under
      optimal mesophilic (28 degrees C) as well as psychrophilic (5 degrees C)
      conditions. However, the exact mechanisms by which this organism is able to
      tolerate such extremes in temperature and high levels of toxic compounds are
      currently not known. In this study, we monitored changes in the fatty acid
      composition of the cell membrane under different extreme growth conditions.
      Arthrobacter chlorophenolicus adapts to differences in temperature and phenol
      concentrations by altering the anteiso/iso ratio of fatty acids in the cell
      membrane to different extents. According to the different physico-chemical
      properties of those two species of branched fatty acids, the bacteria showed an
      increased amount of anteiso fatty acids when grown under psychrophilic conditions
      to decrease the viscosity of their membranes. On the other hand, at higher growth
      temperatures as well as in the presence of toxic concentrations of phenol, 4
      chlorophenol and 4-nitrophenol, the cells adapted their membrane by a dose
      dependent decrease in the anteiso/iso ratio, leading to a more rigid membrane and
      counteracting the fluidity increase caused by the higher temperature and the
      organic solvents.

PMID- 17233724
TI  - Microarray-based analysis of changes in diversity of microbial genes involved in
      organic carbon decomposition following land use/cover changes.
AB  - To increase our understanding of the impact of land use/cover changes on soil
      microbial decomposition genes involved in organic carbon decomposition, we
      analyzed soil samples in four sites with different land cover/use histories in a
      subalpine region of western Sichuan. One site was in a primitive Abies faxoniana
      forest, the second and the third sites were spruce plantations established in
      1960's and 1980's, respectively, and the fourth site was in a cropland dating
      back to 1960's. The genomic DNA from the microbial community was isolated and
      hybridized against a functional gene microarray containing 1,961 probes. There
      were 39, 62, 41, and 28 gene probes with statistically significant positive
      signals and the gene diversity index (H') values were 3.59, 4.04, 3.70 and 3.16
      in primitive forest, spruce plantations established in 1960s and 1980s and
      cropland, respectively. The results suggested that the number of functional genes
      and the gene diversity index were correlated with increasing amounts of soil
      organic carbon, except in the primitive Abies faxoniana forest site. cluster
      analysis demonstrated that primitive forest soil was clustered more closely to
      soil from the spruce plantation established in 1960s.

PMID- 17233725
TI  - Survival of Campylobacter jejuni in different gas mixtures.
AB  - Campylobacter jejuni in fresh chilled chicken meat is known to be a major risk
      factor for human gastrointestinal disease. In the present study, the survival
      under chilled conditions of different C. jejuni strains exposed to different gas
      mixtures usually used for gas packaging of food was examined. Bolton broth and
      fresh, skinless chicken fillets were inoculated with six and four strains,
      respectively, and exposed to the gas mixtures 70/30% O(2)/CO(2), 70/30%
      N(2)/CO(2), and 100% N(2) (the latter only investigated in broth) at
      refrigeration temperature (4-5 degrees C). In broth culture, the strains survived
      significantly longer when exposed to 100% N(2) and 70/30% N(2)/CO(2) than in the
      oxygen-containing gas mixture, 70/30% O(2)/CO(2) (P<0.0001). For the two
      anaerobic gas mixtures, the reductions only reached 0.3-0.8 log(10) CFU mL(-1)
      within the same period. In the presence of oxygen, the numbers of C. jejuni were
      reduced by a minimum of 4.6 log(10) CFU mL(-1) over 21 days. When inoculated onto
      chicken fillets, the C. jejuni strains also died significantly faster in the
      oxygen-containing gas mixture, 70/30% O(2)/CO(2) (P<0.0001), reaching reductions
      of 2.0-2.6 log(10) CFU g(-1) after 8 days. In the gas mixture without oxygen
      (70/30% N(2)/CO(2)), no reductions were observed.

PMID- 17233726
TI  - Binding of host extracellular matrix proteins to Mycoplasma fermentans and its
      effect on adherence to, and invasion of HeLa cells.
AB  - In the present study, we show that intact Mycoplasma fermentans cells have a
      wealth of adhesive interactions with components of the extracellular matrix.
      Mycoplasma fermentans intensively bind plasminogen, and to a lesser extent,
      fibronectin, heparin, and laminin. The binding of collagen type III, IV, or V was
      low. The binding of plasminogen, collagen type III, or collagen type V markedly
      enhanced the adherence of M. fermentans to HeLa cells, whereas the binding of
      fibronectin, heparin, laminin, or collagen IV induced only a small effect on
      mycoplasma adherence. Utilizing plasminogen-treated M. fermentans preparations,
      we detected microorganisms within host HeLa cells by the gentamicin protection
      assay or by confocal laser scanning microscopy of immunofluorescent preparations.
      However, no intracellular M. fermentans was detected when M. fermentans
      preparations treated with fibronectin, heparin, laminin, or collagen type III,
      IV, or V were utilized.

PMID- 17233727
TI  - Investigation of a global collection of nontyphoidal Salmonella of various
      serotypes cultured between 1953 and 2004 for the presence of class 1 integrons.
AB  - In this study, antibiotic resistance profiles, and the presence of class 1
      integrons were determined for 108 Salmonella isolates comprising 37 serotypes
      cultured from a variety of sources between 1953 and 2004. Antibiogram analyses
      showed that all isolates were resistant to streptomycin/spectinomycin. Molecular
      analysis revealed that 50% of the collection contained an integrase-encoding gene
      (int1) and 25% contained class 1 integrons. A Salmonella Wien isolate possessing
      a complete class 1 integron with a dfrA5-ereA2 gene arrangement within the
      variable region was characterized.

PMID- 17233728
TI  - Distribution of virulence-associated genes in Yersinia enterocolitica biovar 1A
      correlates with clonal groups and not the source of isolation.
AB  - Yersinia enterocolitica, an important food- and water-borne enteric pathogen, is
      represented by six biovars viz. 1A, 1B and 2-5. Some biovar 1A strains, despite
      lacking virulence plasmid (pYV) and chromosomal virulence genes, have been
      reported to cause symptoms similar to that produced by isolates belonging to
      known pathogenic biovars. Virulence-associated genes viz. ail, virF, inv, myfA,
      ystA, ystB, ystC, tccC, hreP, fepA, fepD, fes, ymoA and sat were studied in 81
      clinical and nonclinical strains of Y. enterocolitica biovar 1A by PCR
      amplification. All strains lacked ail, virF, ystA and ystC genes. The
      distribution of other genes with respect to clonal groups revealed that four
      genes viz. ystB, hreP, myfA and sat were associated exclusively with strains
      belonging to clonal group A. The clonal groups A and B were differentiated
      previously based on rep (REP-/ERIC) - PCR genomic fingerprinting. The
      distribution of virulence-associated genes, however, did not differ significantly
      between clinical and nonclinical strains. In strains of Y. enterocolitica biovar
      1A, clonal groups seem to reflect virulence potential better than the source
      (clinical vs. nonclinical) of isolation.

PMID- 17233729
TI  - Physical and genetic map of the Staphylococcus xylosus C2a chromosome.
AB  - Staphylococcus xylosus is a ubiquitous bacterium frequently isolated from
      mammalian skin and occurring naturally on meat and dairy products. A physical and
      genetic map of the S. xylosus C2a chromosome was constructed by pulsed-field gel
      electrophoresis analysis after digestion with AscI, ApaI, I-CeuI, SfiI and SmaI
      enzymes and hybridization analysis. The chromosome size was estimated to be
      2868+/-10 kb. Thirty-three genetic markers were mapped. The probable origin of
      replication (oriC) was positioned. Six rrn loci were located, and their
      orientation was determined. The chromosomes of six additional S. xylosus strains
      were also analysed by I-CeuI digestion, and an intraspecies diversity of the
      chromosome size and the number of rrn operons was shown.

PMID- 17233730
TI  - Comparison of cell-specific activity between free-living and attached bacteria
      using isolates and natural assemblages.
AB  - Marine snow aggregates are microbial hotspots that support high bacterial
      abundance and activities. We conducted laboratory experiments to compare cell
      specific bacterial protein production (BPP) and protease activity between free
      living and attached bacteria. Natural bacterial assemblages attached to model
      aggregates (agar spheres) had threefold higher BPP and two orders of magnitude
      higher protease activity than their free-living counterpart. These observations
      could be explained by preferential colonization of the agar spheres by bacteria
      with inherently higher metabolic activity and/or individual bacteria increasing
      their metabolism upon attachment to surfaces. In subsequent experiments, we used
      four strains of marine snow bacteria isolates to test the hypothesis that
      bacteria could up- and down-regulate their metabolism while on and off an
      aggregate. The protease activity of attached bacteria was 10-20 times higher than
      that of free-living bacteria, indicating that the individual strains could
      increase their protease activity within a short time (2 h) upon attachment to
      surfaces. Agar spheres with embedded diatom cells were colonized faster than
      plain agar spheres and the attached bacteria were clustered around the agar
      embedded diatom cells, indicating a chemosensing response. Increased protease
      activity and BPP allow attached bacteria to quickly exploit aggregate resources
      upon attachment, which may accelerate remineralization of marine snow and reduce
      the downward carbon fluxes.

PMID- 17233731
TI  - Peptidoglycan lytic activity of the Pseudomonas aeruginosa phage phiKZ gp144
      lytic transglycosylase.
AB  - The gp144 endolysin gene from the Pseudomonas aeruginosa phage phiKZ was cloned
      and studies of gp144 expression into Escherichia coli showed host cell lysis. The
      gp144 protein was purified directly from the culture supernatant and from the
      bacterial cell pellet and showed in vitro antibacterial lytic activity against P.
      aeruginosa bacteria and degraded purified peptidoglycan of Gram-negative
      bacteria. MS analysis identified the gp144 peptidoglycan cleavage site and
      confirmed a lytic transglycosylase enzyme. Studies of gp144 expression in the
      presence of sodium azide (NaN(3)), an inhibitor of the protein export machinery,
      and into an E. coli MM52 secA(ts) mutant at permissive and restrictive
      temperatures showed that gp144 was secreted independently of the Sec system. The
      solution conformation of purified gp144 analyzed by circular dichroism
      spectroscopy was 61% in alpha-helical content, and showed a 72% decrease when
      interacting with dimyristoylphosphatidylglycerol (DMPG), one of the major
      components of bacterial membranes and less than 10% with
      dimyristoylphosphatidylcholine (DMPC) found in eukaryotic membranes. Membrane
      vesicles of DMPG anionic lipids containing calcein indicated that gp144 caused a
      rapid release of fluorescent calcein when interacting with synthetic membranes.
      These results indicated that gp144 from phiKZ is a lytic transglycosylase capable
      of interacting with and disorganizing bacterial membranes and has potential as an
      antipseudomonal in phage therapy.

PMID- 17233732
TI  - Inactivation of the nodH gene in Sinorhizobium sp. BR816 enhances symbiosis with
      Phaseolus vulgaris L.
AB  - Sulfate modification on Rhizobium Nod factor signaling molecules is not a
      prerequisite for successful symbiosis with the common bean (Phaseolus vulgaris
      L.). However, many bean-nodulating rhizobia, including the broad host strain
      Sinorhizobium sp. BR816, produce sulfated Nod factors. Here, we show that the
      nodH gene, encoding a sulfotransferase, is responsible for the transfer of
      sulfate to the Nod factor backbone in Sinorhizobium sp. BR816, as was shown for
      other rhizobia. Interestingly, inactivation of nodH enables inoculated bean
      plants to fix significantly more nitrogen under different experimental setups.
      Our studies show that nodH in the wild-type strain is still expressed during the
      later stages of symbiosis. This is the first report on enhanced nitrogen fixation
      by blocking Nod factor sulfation.

PMID- 17233733
TI  - Overlapping substrate specificity for sucrose and maltose of two binding protein
      dependent sugar uptake systems in Streptococcus mutans.
AB  - Sugar metabolism by Streptococcus mutans is associated with tooth decay. The most
      abundant sugars in the human diet are sucrose and maltose, a derivative of
      starch. Previously, we reported a binding protein-dependent transport system
      (msm) in S. mutans that transports sucrose and maltose, but its associated
      enzymes do not metabolize maltose. By searching the S. mutans genomic sequence
      for a maltose system (mal), we found a gene cluster encoding proteins with
      homology to those of msm and the Escherichia coli maltose system. Mutants were
      constructed by deleting msm or mal, or both, and tested for sugar utilization.
      Deletion of the mal system diminished the ability of S. mutans to ferment
      maltose, but deletion of only the mal transporter genes or msm showed reduced
      utilization of chromogenic maltosides. Maltose, sucrose, glucose, fructose,
      mannose, and N-acetyl glucosamine inhibited utilization of chromogenic maltosides
      by the wild-type strain and mutants. In conclusion, the two binding protein
      dependent systems in S. mutans appear to transport collaboratively their common
      substrate sugars, notably sucrose and maltose.

PMID- 17233734
TI  - Enhancement of riboflavin production by overexpression of acetolactate synthase
      in a pta mutant of Bacillus subtilis.
AB  - Genetic alterations of carbon flux into the acetoin biosynthesis pathway as a
      possible means to reduce acid accumulation were investigated in the riboflavin
      producing Bacillus subtilis during growth on glucose. The lower rates of cell
      growth and riboflavin production were found in the pta-disrupted mutant while the
      rate of acetate formation was reduced. In contrast, acid accumulation was
      significantly reduced, to one-fifth that of the parental strain RH33::[pRB63](n),
      and a 50% increase in the riboflavin yield was obtained when the expression of
      the gene encoding acetolactate synthase was increased in the pta-disrupted
      mutant. Metabolic analysis, together with enzyme activity assays, indicated that
      the tricarboxylic acid cycle fluxes are significantly increased in response to
      acetolactate synthase overexpression in pta-disrupted mutant. Moreover, the
      intracellular ATP-to-ADP ratio also increased 5.8-fold. The high concentration of
      ATP could explain the increased riboflavin production.

PMID- 17233735
TI  - Diversity and distribution of Burkholderia cepacia complex in the rhizosphere of
      rice and maize.
AB  - A survey of Burkholderia cepacia complex (Bcc) species was conducted in
      agricultural fields within Hangzhou, China. Out of the 251 bacterial isolates
      recovered on the selective media from the rhizosphere of rice and maize, 112 of
      them were assigned to Bcc by PCR assays. The species composition of the Bcc
      isolates was analyzed by a combination of recA-restriction fragment length
      polymorphism assays, species-specific PCR tests and recA gene sequencing. The
      results revealed that the majority belong to B. cepacia, Burkholderia cenocepacia
      recA lineage IIIB, Burkholderia vietnamiensis and Burkholderia pyrrocinia.
      Burkholderia cenocepacia and B. vietnamiensis dominated the rhizosphere of maize
      and rice, respectively, indicating that species composition and abundance of Bcc
      may vary dramatically in different crop rhizospheres. In addition, one isolate
      (R456) formed a single discrete cluster within the phylogenetic analysis of the
      Bcc recA gene, and it may belong to a new genomovar.

PMID- 17233736
TI  - Elimination of channel-forming activity by insertional inactivation of the p66
      gene in Borrelia burgdorferi.
AB  - P66 is a chromosomally encoded 66-kDa integral outer membrane protein of the Lyme
      disease agent Borrelia burgdorferi exhibiting channel-forming activity. Herein,
      we inactivated and subsequently complemented the p66 gene in the B31-A (WT)
      strain. The P66 protein was also inactivated in two other channel-forming protein
      mutant strains, P13-18 (Deltap13) and Deltabba01, and then compared with the
      channel-forming activities of wild-type and various p66 mutant strains. We
      further investigated the ion-selectivity of native, purified P66. In conclusion,
      we show that the porin activity of P66 is eliminated by insertional inactivation
      and that this activity can be rescued by gene complementation.

PMID- 17233737
TI  - T-cell migration: a naive paradigm?
AB  - Naive T cells have long been thought to recirculate exclusively between secondary
      lymphoid organs via the lymph and blood. Evidence is now emerging that this view
      may be too simplistic and that naive T cells routinely traffic through non
      lymphoid organs in a manner similar to that of memory T cells, albeit in lower
      numbers. This represents a fundamental shift in the current paradigm of T-cell
      migration through different types of tissue. This review summarizes these recent
      findings, along with the similarities and differences in migratory properties of
      naive and memory T cells, and discusses how and why naive T cells might access
      non-lymphoid tissues.

PMID- 17233738
TI  - Essential crosstalk between myeloid and lymphoid cells for development of chronic
      colitis in myeloid-specific signal transducer and activator of transcription 3
      deficient mice.
AB  - Dysregulated cytokine responsiveness by myeloid cells can be a trigger for the
      development of chronic inflammation as well as inflammatory bowel disease. Thus,
      mice with a myeloid-specific defect in signal transducer and activator of
      transcription (Stat) 3 develop spontaneous colitis secondary to the inability of
      myeloid cells to respond to the immunosuppressive cytokine interleukin-10. We now
      examined whether the inflammation caused by Stat3-deficient macrophages is cell
      autonomous or dependent on their interaction with lymphocytes. For this purpose,
      myeloid-specific Stat3-deficient mice (LysMcre/Stat3(flox) mice) were
      intercrossed with RAG-1 knockout mice to generate LysMcre/Stat3(flox) RAG(-/-)
      mice. In these mutants and LysMcre/Stat3(flox) littermate control mice we
      determined the onset and severity of spontaneous chronic enterocolitis, and the
      reaction to dextran sodium sulphate (DSS)-induced epithelial damage, as well as
      to lipopolysaccharide (LPS) challenge. In contrast to LysMcre/Stat3(flox) mice,
      LysMcre/Stat3(flox) RAG(-/-) animals are protected from chronic enterocolitis.
      Although they respond to oral dextran sulphate with acute colitis symptoms, the
      inflammation heals similarly to wild type mice whereas LysMcre/Stat3(flox) mice
      exhibit continued colitis pathology. In addition, the hyperreactivity of
      LysMcre/Stat3(flox) mice to LPS-challenge in vivo was less severe in the absence
      of lymphocytes. Despite clear differences in the strength of inflammatory
      responses, macrophages of both LysMcre/Stat3(flox) mice and LysMcre/Stat3(flox)
      RAG(-/-) animals exhibited increased costimulatory capacity. In conclusion, our
      findings demonstrate that Stat3-deficient myeloid cells alone are not capable of
      inducing the severe pathology seen in LysMcre/Stat3(flox) mice. Yet when these
      cells can interact with lymphocytes their increased costimulatory potential will
      trigger an overshooting inflammatory response.

PMID- 17233740
TI  - Fas ligand exerts its pro-inflammatory effects via neutrophil recruitment but not
      activation.
AB  - Fas ligand (FasL) expression induces apoptosis of activated T cells and has been
      suggested as a strategy to inhibit graft rejection. Unfortunately, the use of
      FasL to confer 'immune privilege' in this setting has been hampered by the
      finding that it may also provoke a destructive granulocytic response. While the
      Fas/FasL-mediated apoptotic pathways are well defined, the pro-inflammatory
      effects of FasL are poorly understood. Our aim in this study was to define in
      vitro the biological effects of FasL on neutrophil recruitment and activation.
      DAP-3 cells expressing human FasL on the cell membrane (mFasL) potently induced
      apoptosis in human neutrophils and in activated T lymphocytes. Recombinant human
      soluble FasL (sFasL), by contrast, was a very weak inducer of apoptosis, even at
      high concentrations. This latter observation suggests that cleavage of mFasL by
      naturally occurring matrix metalloproteinases may serve to down-regulate FasL
      activity in vivo. However, in the presence of a cross-linking antibody, the
      efficiency of apoptosis-induction by sFasL was greatly increased, suggesting that
      the lesser pro-apoptotic potency of sFasL reflects an inability to induce
      trimerization of the Fas receptor. With regard to pro-inflammatory effects, we
      found that sFasL is a potent neutrophil chemoattractant and, given that it
      induces little apoptosis, the dominance of sFasL over mFasL may mean that graft
      infiltrating neutrophils will survive to mediate inflammation. Neither sFasL nor
      mFasL produced neutrophil activation as assessed by chemiluminescence assay. This
      suggests that neutrophils recruited to an inflammatory site by FasL will be
      activated by mechanisms other than Fas-FasL signalling.

PMID- 17233739
TI  - Use of multiple peptides containing T cell epitopes is a feasible approach for
      peptide-based immunotherapy in Can f 1 allergy.
AB  - We have previously shown that the major dog allergen Can f 1 contains seven T
      cell epitope regions, none of which was preferentially recognized. To identify
      the immune characteristics of Can f 1 epitopes and to verify their suitability
      for peptide-based allergen immunotherapy, short-term T cell lines were generated
      with epitope-containing peptides from peripheral blood mononuclear cells of Can f
      1 skinprick test-positive allergic and healthy control subjects. The lines were
      examined for their proliferative capacity and cytokine production upon
      stimulation with the allergen peptide, a homologous peptide from human tear
      lipocalin (TL) and Can f 1 and TL proteins. Can f 1 peptides induced
      proliferation of T cells and gave rise to T cell lines with comparable
      efficiencies. In particular, the T cell lines of allergic subjects induced with
      p33-48 and p107-122 favoured the production of interferon-gamma and interleukin
      10, respectively. A greater number of Can f 1-specific T cell lines were
      generated from allergic than from healthy individuals. Two p107-122-induced Can f
      1-specific T cell lines also reacted to a homologous peptide of human TL. Our
      results suggest that several T cell epitope-containing peptides should be used in
      combination for specific immunotherapy in Can f 1 allergy.

PMID- 17233741
TI  - On a key postulate of T-cell receptor restrictive function: the V-gene loci act
      as a single pool encoding recognition of the polymorphic alleles of the species
      major histocompatibility complex.
AB  - The proposition that single Valpha or Vbeta gene segments specify the recognition
      of the allele-specific determinants expressed on the major histocompatibility
      complex-encoded restricting elements of the species has as its consequence a
      totally different picture of the functioning of the T-cell receptor. This
      commentary justifies this assumption and outlines some of its most important
      consequences.

PMID- 17233742
TI  - The role of liver-derived regulatory dendritic cells in prevention of type 1
      diabetes.
AB  - Development of type 1 diabetes has been attributed to T-cell-mediated
      autoimmunity, which is regulated by antigen-presenting cells. To study the role
      of liver-derived B220(+) regulatory dendritic cells (DCs) in the development of
      diabetes in non-obese diabetic (NOD) mice, we found that liver 220(+) DCs could
      easily be propagated from young NOD mice, but that such propagation was extremely
      difficult from mice older than 11 weeks, when insulitis began. This was not
      simply an age-related phenomenon, because liver B220(+) DCs were readily
      propagated from both young and old congenic non-obese diabetic-resistant (NOR)
      and normal BALB/c mice. It was therefore speculated that the development of
      diabetes might be associated with a lack of precursors of B220(+) DC in the liver
      in this animal model. Unfortunately, the specific marker for precursors of liver
      B220(+) DC has not been identified. An alternative approach to supplement liver
      B220(+) DCs by intravenous administration significantly inhibited the development
      of diabetes by inducing T-cell hyporesponsiveness via enhancement of their
      apoptotic death. Liver B220(+) DCs were capable of effectively presenting
      antigens but, unlike plasmacytoid DCs, did not express CD11c and were not
      interferon-alpha producers. These observations may throw new light on the
      aetiopathology of type 1 diabetes.

PMID- 17233744
TI  - The GacS sensor kinase controls phenotypic reversion of small colony variants
      isolated from biofilms of Pseudomonas aeruginosa PA14.
AB  - The GacS/GacA two-component regulatory system in pseudomonads regulates genes
      involved in virulence, secondary metabolism and biofilm formation. Despite these
      regulatory functions, some Pseudomonas species are prone to spontaneous
      inactivating mutations in gacA and gacS. A gacS(-) strain of Pseudomonas
      aeruginosa PA14 was constructed to study the physiological role of this sensor
      histidine kinase. This loss-of-function mutation was associated with
      hypermotility, reduced production of acylhomoserine lactones, impaired biofilm
      maturation, and decreased antimicrobial resistance. Biofilms of the gacS(-)
      mutant gave rise to phenotypically stable small colony variants (SCVs) with
      increasing frequency when exposed to silver cations, hydrogen peroxide, human
      serum, or certain antibiotics (tobramicin, amikacin, azetronam, ceftrioxone,
      oxacilin, piperacillin or rifampicin). When cultured, the SCV produced thicker
      biofilms with greater cell density and greater antimicrobial resistance than did
      the wild-type or parental gacS(-) strains. Similar to other colony morphology
      variants described in the literature, this SCV was less motile than the wild-type
      strain and autoaggregated in broth culture. Complementation with gacS in trans
      restored the ability of the SCV to revert to a normal colony morphotype. These
      findings indicate that mutation of gacS is associated with the occurrence of
      stress-resistant SCV cells in P. aeruginosa biofilms and suggests that in some
      instances GacS may be necessary for reversion of these variants to a wild-type
      state.

PMID- 17233745
TI  - Evidence for chemoautotrophic symbiosis in a Mediterranean cold seep clam
      (Bivalvia: Lucinidae): comparative sequence analysis of bacterial 16S rRNA, APS
      reductase and RubisCO genes.
AB  - Symbioses between lucinid clams (Bivalvia: Lucinidae) and autotrophic sulphide
      oxidizing bacteria have mainly been studied in shallow coastal species, and
      information regarding deep-sea species is scarce. Here we study the symbiosis of
      a clam, resembling Lucinoma kazani, which was recently collected in sediment
      cores from new cold-seep sites in the vicinity of the Nile deep-sea fan, eastern
      Mediterranean, at depths ranging from 507 to 1691 m. A dominant bacterial
      phylotype, related to the sulphide-oxidizing symbiont of Lucinoma aequizonata,
      was identified in gill tissue by comparative 16S rRNA gene sequence analysis. A
      second phylotype, related to spirochete sequences, was identified twice in a
      library of 94 clones. Comparative analyses of gene sequences encoding the APS
      reductase alpha subunit and ribulose-1,5-bisphosphate carboxylase oxygenase
      support the hypothesis that the dominant symbiont can perform sulphide oxidation
      and autotrophy. Transmission electron micrographs of gills confirmed the
      dominance of sulphide-oxidizing bacteria, which display typical vacuoles, and
      delta(13)C values measured in gill and foot tissue further support the hypothesis
      for a chemoautotrophic-sourced host carbon nutrition.

PMID- 17233746
TI  - Bacterial community structure associated with the Antarctic soft coral, Alcyonium
      antarcticum.
AB  - The structure and composition of microbial communities inhabiting the soft coral
      Alcyonium antarcticum were investigated across three differentially contaminated
      sites within McMurdo Sound, Antarctica. Diverse microbial communities were
      revealed at all sites using culture-based analysis, denaturing gradient gel
      electrophoresis (DGGE), 16S rRNA gene clone-library analysis, and FISH.
      Phylogenetic analysis of isolates and retrieved sequences demonstrated close
      affiliation with known psychrophiles from the Antarctic environment and high
      similarity to Gammaproteobacteria clades of sponge-associated microorganisms. The
      majority of bacteria detected with all techniques reside within the
      Gammaproteobacteria, although other phylogenetic groups including Alpha- and
      Betaproteobacteria, Bacteroidetes, Firmicutes, Actinomycetales, Planctomycetes,
      and Chlorobi and bacteria from the functional group of sulfate-reducing bacteria
      were also present. Multivariate (nMDS) analysis of DGGE banding patterns and
      principal component analysis of quantitative FISH data revealed no distinct
      differences in community composition between differentially contaminated sites.
      Rather, conserved coral-associated bacterial groups were observed within and
      between sites, providing evidence to support specific coral-microbial
      interactions. This is the first investigation of microbial communities associated
      with Antarctic soft corals, and the results suggest that spatially stable
      microbial associations exist across an environmental impact gradient.

PMID- 17233747
TI  - Metabolically active microbial communities in uranium-contaminated subsurface
      sediments.
AB  - In order to develop effective bioremediation strategies for radionuclide
      contaminants, the composition and metabolic potential of microbial communities
      need to be better understood, especially in highly contaminated subsurface
      sediments for which little cultivation-independent information is available. In
      this study, we characterized metabolically active and total microbial communities
      associated with uranium-contaminated subsurface sediments along geochemical
      gradients. DNA and RNA were extracted and amplified from four sediment-depth
      intervals representing moderately acidic (pH 3.7) to near-neutral (pH 6.7)
      conditions. Phylotypes related to Proteobacteria (Alpha-, Beta-, Delta- and
      Gammaproteobacteria), Bacteroidetes, Actinobacteria, Firmicutes and
      Planctomycetes were detected in DNA- and RNA-derived clone libraries. Diversity
      and numerical dominance of phylotypes were observed to correspond to changes in
      sediment geochemistry and rates of microbial activity, suggesting that
      geochemical conditions have selected for well-adapted taxa. Sequences closely
      related to nitrate-reducing bacteria represented 28% and 43% of clones from the
      total and metabolically active fractions of the microbial community,
      respectively. This study provides the first detailed analysis of total and
      metabolically active microbial communities in radionuclide-contaminated
      subsurface sediments. Our microbial community analysis, in conjunction with rates
      of microbial activity, points to several groups of nitrate-reducers that appear
      to be well adapted to environmental conditions common to radionuclide
      contaminated sites.

PMID- 17233748
TI  - Characterization of marine bacteria and the activity of their enzyme systems
      involved in degradation of the algal storage glucan laminarin.
AB  - The algal storage glucan laminarin is one of the most abundant carbon sources for
      marine prokaryotes. Its degradation was investigated in bacteria isolated during
      and after a spring phytoplankton bloom in the coastal North Sea. On average, 13%
      of prokaryotes detected by epifluorescence counts were able to grow in Most
      Probable Number dilution series on laminarin as sole carbon source. Several
      bacterial strains were isolated from different dilutions, and phylogenetic
      characterization revealed that they belonged to different phylogenetic groups.
      The activity of the laminarin-degrading enzyme systems was further characterized
      in three strains of Vibrio sp. that were able to grow on laminarin as sole carbon
      source. At least two types of activity were detected upon degradation of
      laminarin: release of glucose, and release of glucans larger than glucose. The
      expression of laminarinase activity was dependent on the presence of the
      substrate, and was repressed by the presence of glucose. In addition, low levels
      of activity were expressed under starvation conditions. Laminarinase enzymes
      showed minimal activity on substrates with similar glucosidic bonds to those of
      laminarin, but different sizes and secondary and/or tertiary structures. The
      characteristics found in these enzyme systems may help to elucidate factors
      hampering rapid carbohydrate degradation by prokaryotes.

PMID- 17233749
TI  - 16S rRNA gene-based analysis of mucosa-associated bacterial community and
      phylogeny in the chicken gastrointestinal tracts: from crops to ceca.
AB  - Mucosa-associated microbiota from different regions of the gastrointestinal (GI)
      tract of adult broilers was studied by analysis of 16S rRNA gene sequences. The
      microbiota mainly comprised Gram-positive bacteria along the GI tract. Fifty-one
      operational taxonomic units (OTUs) (from 98 clones) were detected in the ceca, as
      compared with 13 OTUs (from 49 clones) in the crops, 11 OTUs (from 51 clones) in
      the gizzard, 14 OTUs (from 52 clones) in the duodenum, 12 OTUs (from 50 clones)
      in the jejunum and nine OTUs (from 50 clones) in the ileum. Ceca were dominantly
      occupied by clostridia-related sequences (40%) with other abundant sequences
      being related to Faecalibacterium prausnitzii (14%), Escherichia coli (11%),
      lactobacilli (7%) and Ruminococcus (6%). Lactobacilli were predominant in the
      upper GI tract and had the highest diversity in the crop. Both Lactobacillus
      aviarius and Lactobacillus salivarius were the predominant species among
      lactobacilli. Candidatus division Arthromitus was also abundant in the jejunum
      and ileum.

PMID- 17233750
TI  - In vitro suppression of fungi caused by combinations of apparently non
      antagonistic soil bacteria.
AB  - We hypothesized that apparently non-antagonistic soil bacteria may contribute to
      suppression of fungi during competitive interactions with other bacteria. Four
      soil bacteria (Brevundimonas sp., Luteibacter sp., Pedobacter sp. and Pseudomonas
      sp.) that exhibited little or no visible antifungal activity on different agar
      media were prescribed. Single and mixed strains of these species were tested for
      antagonism on a nutrient-poor agar medium against the plant pathogenic fungi
      Fusarium culmorum and Rhizoctonia solani and the saprotrophic fungus Trichoderma
      harzianum. Single bacterial strains caused little to moderate growth reduction of
      fungi (quantified as ergosterol), most probably due to nutrient withdrawal from
      the media. Growth reduction of fungi by the bacterial mixture was much stronger
      than that by the single strains. This appeared to be mostly due to competitive
      interactions between the Pseudomonas and Pedobacter strains. We argue that
      cohabitation of these strains triggered antibiotic production via interspecific
      interactions and that the growth reduction of fungi was a side-effect caused by
      the sensitivity of the fungi to bacterial secondary metabolites. Induction of
      gliding behavior in the Pedobacter strain by other strains was also observed. Our
      results indicate that apparently non-antagonistic soil bacteria may be important
      contributors to soil suppressiveness and fungistasis when in a community context.

PMID- 17233751
TI  - Epiphytic fitness of a biological control agent of fire blight in apple and pear
      orchards under Mediterranean weather conditions.
AB  - The behaviour of Pseudomonas fluorescens EPS62e was investigated in apple and
      pear orchards under Mediterranean climatic conditions. The trials studied the
      influence of weather conditions, plant host species, presence of indigenous
      microbial community and spread from treated to nontreated trees on colonization
      and survival. Population dynamics were assessed by real-time PCR and CFU-counting
      methods. With inoculated flowers, weather conditions were optimal for
      colonization, and EPS62e established high and stable population levels around
      10(8) CFU per organ, according to both methods of analysis. The plant host
      species did not influence the colonization rate, and the biocontrol agent
      dominated the microbial communities of blossoms, representing up to 100% of the
      total cultivable population. With inoculated leaves, the EPS62e population
      decreased to nondetectable levels 30 days after treatment according to both
      methods used. EPS62e spread moderately in the orchard, being detected in
      nontreated flowers of trees 15-35 m from the inoculation site. The combined use
      of real-time PCR and CFU-counting methods of analysis permitted the
      identification of three physiological states for EPS62e in the field, which
      consisted of active colonization, survival and entry into a viable but
      nonculturable state, and cell death.

PMID- 17233752
TI  - Environmental distribution of the trichloroethene reductive dehalogenase gene
      (tceA) suggests lateral gene transfer among Dehalococcoides.
AB  - The trichloroethene reductive dehalogenase gene (tceA) of Dehalococcoides spp.
      was detected in 12 of 21 trichloroethene-to-ethene dechlorinating enrichment
      cultures established from aquifer and sediment samples collected from diverse
      geographic locations in the USA. Analysis of the tceA chromosomal regions
      indicated that the tceA genes shared greater than 95% sequence identity, and all
      shared identical tceAB spacer sequences and tceB genes downstream of tceA. A
      putative transposable element (PTE) was present 1077 bp downstream of the tceB
      stop codon in three of eight chromosomal regions analyzed. Sequence identity was
      interrupted downstream of tceB and upstream or downstream of the PTE, suggesting
      that intrachromosomal or interchromosomal transfer of tceAB had occurred.

PMID- 17233753
TI  - Structured incorporation of prior information in relationship identification
      problems.
AB  - The objective of this paper is to show how various sources of information can be
      modelled and integrated to address relationship identification problems.
      Applications come from areas as diverse as evolution and conservation research,
      genealogical research in human, plant and animal populations, and forensic
      problems including paternity cases, identification following disasters, family
      reunions and immigration issues. We propose assigning a prior probability
      distribution to the sample space of pedigrees, calculating the likelihood based
      on DNA data using available software and posterior probabilities using Bayes'
      Theorem. Our emphasis here is on the modelling of this prior information in a
      formal and consistent manner. We introduce the distinction between local and
      global prior information, whereby local information usually applies to particular
      components of the pedigree and global prior information refers to more general
      features. When it is difficult to decide on a prior distribution, robustness to
      various choices should be studied. When suitable prior information is not
      available, a flat prior can be used which will then correspond to a strict
      likelihood approach. In practice, prior information is often considered for these
      problems, but in a generally ad hoc manner. This paper offers a consistent
      alternative. We emphasise that many practical problems can be addressed using
      freely available software.

PMID- 17233754
TI  - Signatures of positive selection in genes associated with human skin pigmentation
      as revealed from analyses of single nucleotide polymorphisms.
AB  - Phenotypic variation between human populations in skin pigmentation correlates
      with latitude at the continental level. A large number of hypotheses involving
      genetic adaptation have been proposed to explain human variation in skin colour,
      but only limited genetic evidence for positive selection has been presented. To
      shed light on the evolutionary genetic history of human variation in skin colour
      we inspected 118 genes associated with skin pigmentation in the Perlegen dataset,
      studying single nucleotide polymorphisms (SNPs), and analyzed 55 genes in detail.
      We identified eight genes that are associated with the melanin pathway (SLC45A2,
      OCA2, TYRP1, DCT, KITLG, EGFR, DRD2 and PPARD) and presented significant
      differences in genetic variation between Europeans, Africans and Asians. In six
      of these genes we detected, by means of the EHH test, variability patterns that
      are compatible with the hypothesis of local positive selection in Europeans
      (OCA2, TYRP1 and KITLG) and in Asians (OCA2, DCT, KITLG, EGFR and DRD2), whereas
      signals were scarce in Africans (DCT, EGFR and DRD2). Furthermore, a
      statistically significant correlation between genotypic variation in four
      pigmentation candidate genes and phenotypic variation of skin colour in 51
      worldwide human populations was revealed. Overall, our data also suggest that
      light skin colour is the derived state and is of independent origin in Europeans
      and Asians, whereas dark skin color seems of unique origin, reflecting the
      ancestral state in humans.

PMID- 17233755
TI  - A bidirectional corridor in the Sahel-Sudan belt and the distinctive features of
      the Chad Basin populations: a history revealed by the mitochondrial DNA genome.
AB  - The Chad Basin was sparsely inhabited during the Stone Age, and its continual
      settlement began with the Holocene. The role played by Lake Chad in the history
      and migration patterns of Africa is still unclear. We studied the mitochondrial
      DNA (mtDNA) variability in 448 individuals from 12 ethnically and/or economically
      (agricultural/pastoral) different populations from Cameroon, Chad, Niger and
      Nigeria. The data indicate the importance of this region as a corridor connecting
      East and West Africa; however, this bidirectional flow of people in the Sahel
      Sudan Belt did not erase features peculiar to the original Chad Basin
      populations. A new sub-clade, L3f2, is described, which together with L3e5 is
      most probably autochthonous in the Chad Basin. The phylogeography of these two
      sub-haplogroups seems to indicate prehistoric expansion events in the Chad Basin
      around 28,950 and 11,400 Y.B.P., respectively. The distribution of L3f2 is
      virtually restricted to the Chad Basin alone, and in particular to Chadic
      speaking populations, while L3e5 shows evidence for diffusion into North Africa
      at about 7,100 Y.B.P. The absence of L3f2 and L3e5 in African-Americans, and the
      limited number of L-haplotypes shared between the Chad Basin populations and
      African-Americans, indicate the low contribution of the Chad region to the
      Atlantic slave trade.

PMID- 17233756
TI  - Salmonella trafficking is defined by continuous dynamic interactions with the
      endolysosomal system.
AB  - Following invasion of non-phagocytic host cells, Salmonella enterica survives and
      replicates within a phagosome-like compartment known as the Salmonella-containing
      vacuole (SCV). It is now well established that SCV biogenesis, like phagosome
      biogenesis, involves sequential interactions with the endocytic pathway. However,
      Salmonella is believed to limit these interactions and, in particular, to avoid
      fusion of terminal lysosomes with the SCV. In this study, we reassessed this
      process using a high-resolution live-cell imaging approach and found an
      unanticipated level of interaction between the SCV and the endocytic pathway.
      Direct interactions, in which late endosomal/lysosomal content was transferred to
      SCVs, were detected within 30 min of invasion and continued for several hours.
      Mechanistically, these interactions were very similar to phagosome-lysosome
      fusion because they were accompanied by rapid acidification of the SCV, could be
      blocked by chemical perturbation of microtubules or vacuolar acidification and
      involved the smallGTPase Rab7. In comparison with vacuoles containing
      internalized Escherichia coli or heat-killed Salmonella, SCVs did show some delay
      of fusion and acidification, although, this appeared to be independent of either
      type III secretion system. These results provide compelling evidence that
      inhibition of SCV-lysosome fusion is not the major determinant in establishment
      of the Salmonella replicative niche in epithelial cells.

PMID- 17233757
TI  - Host ABCE1 is at plasma membrane HIV assembly sites and its dissociation from Gag
      is linked to subsequent events of virus production.
AB  - In primate cells, assembly of a single HIV-1 capsid involves multimerization of
      thousands of Gag polypeptides, typically at the plasma membrane. Although studies
      support a model in which HIV-1 assembly proceeds through complexes containing Gag
      and the cellular adenosine triphosphatase ABCE1 (also termed HP68 or ribonuclease
      L inhibitor), whether these complexes constitute true assembly intermediates
      remains controversial. Here we demonstrate by pulse labeling in primate cells
      that a population of Gag associates with endogenous ABCE1 within minutes of
      translation. In the next approximately 2 h, Gag-ABCE1 complexes increase in size
      to approximately that of immature capsids. Dissociation of ABCE1 from Gag
      correlates closely with Gag processing during virion maturation and occurs much
      less efficiently when the HIV-1 protease is inactivated. Finally, quantitative
      double-label immunogold electron microscopy reveals that ABCE1 is recruited to
      sites of assembling wild-type Gag at the plasma membrane but not to sites of an
      assembly-defective Gag mutant at the plasma membrane. Together these findings
      demonstrate that a population of Gag present at plasma membrane sites of assembly
      associates with ABCE1 throughout capsid formation until the onset of virus
      maturation, which is then followed by virus release. Moreover, the data suggest a
      linkage between Gag-ABCE1 dissociation and subsequent events of virion
      production.

PMID- 17233758
TI  - Oligomerization is a specific requirement for apical sorting of glycosyl
      phosphatidylinositol-anchored proteins but not for non-raft-associated apical
      proteins.
AB  - Protein apical sorting in polarized epithelial cells is mediated by two different
      mechanisms, raft dependent and raft independent. In Madin-Darby canine kidney
      (MDCK) cells, an essential step for apical sorting of glycosyl
      phosphatidylinositol (GPI)-anchored proteins (GPI-APs) is their coalescence into
      high-molecular-weight (HMW) oligomers. Here we show that this mechanism is also
      functional in Fischer rat thyroid cells, which possess a different sorting
      phenotype compared with MDCK cells. We demonstrate that, as in MDCK cells, both
      apical and basolateral GPI-APs associate with detergent-resistant microdomains,
      but that only the apical proteins are able to oligomerize into HMW complexes
      during their passage through the medial Golgi. We also show that oligomerization
      is a specific requirement for apical sorting of GPI-APs and is not used by
      transmembrane, non-raft-associated apical proteins.

PMID- 17233759
TI  - PKC anchoring to GluR4 AMPA receptor subunit modulates PKC-driven receptor
      phosphorylation and surface expression.
AB  - Changes in the synaptic content of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate (AMPA)-type glutamate receptors lead to synaptic efficacy
      modifications, involved in synaptic plasticity mechanisms believed to underlie
      learning and memory formation. Early in development, GluR4 is highly expressed in
      the hippocampus, and GluR4-containing AMPA receptors are inserted into synapses.
      During synapse maturation, the number of AMPA receptors at the synapse is
      dynamically regulated, and both addition and removal of receptors from
      postsynaptic sites occur through regulated mechanisms. GluR4 delivery to synapses
      in rat hippocampal slices was shown to require protein kinase A (PKA)-mediated
      phosphorylation of GluR4 at serine 842 (Ser842). Protein kinase C (PKC) can also
      phosphorylate Ser842, and we have shown that PKCgamma can associate with GluR4.
      Here we show that activation of PKC in retina neurons, or in human embryonic
      kidney 293 cells cotransfected with GluR4 and PKCgamma, increases GluR4 surface
      expression and Ser842 phosphorylation. Moreover, mutation of amino acids R821A,
      K825A and R826A at the GluR4 C-terminal, within the interacting region of GluR4
      with PKCgamma, abolishes the interaction between PKCgamma and GluR4 and prevents
      the stimulatory effect of PKCgamma on GluR4 Ser842 phosphorylation and surface
      expression. These data argue for a role of anchored PKCgamma in Ser842
      phosphorylation and targeting to the plasma membrane. The triple GluR4 mutant is,
      however, phosphorylated by PKA, and it is targeted to the synapse in CA1
      hippocampal neurons in organotypic rat hippocampal slices. The present findings
      show that the interaction between PKCgamma and GluR4 is specifically required to
      assure PKC-driven phosphorylation and surface membrane expression of GluR4.

PMID- 17233760
TI  - Extracellular glycosylphosphatidylinositol-anchored mannoproteins and proteases
      of Cryptococcus neoformans.
AB  - Extracellular proteins of Cryptococcus neoformans are involved in the
      pathogenesis of cryptococcosis, and some are immunoreactive antigens that may
      potentially serve as candidates for vaccine development. To further study the
      extracellular proteome of the human fungal pathogen Cry. neoformans, we conducted
      a proteomic analysis of secreted and cell wall-bound proteins with an acapsular
      strain of Cry. neoformans. Proteins were identified from both intact cells and
      cell walls. In both cases, extracellular proteins were removed with trypsin or
      beta-glucanase, and then all proteins/peptides were purified by solid-phase
      extraction, spin dialysis, and HPLC, and identified by liquid chromatography-mass
      spectrometry. This study identified 29 extracellular proteins with a predicted N
      terminal signal sequence and also a predicted glycosylphosphatidylinositol anchor
      motif in more than half. Among the novel proteins identified were five
      glycosylphosphatidylinositol-anchored proteins with extensive Ser/Thr-rich
      regions but no apparent functional domains, a glycosylphosphatidylinositol
      anchored aspartic protease, and a metalloprotease with structural similarity to
      an elastinolytic metalloprotease of Aspergillus fumigatus. This study suggests
      that Cry. neoformans has the machinery required to target
      glycosylphosphatidylinositol-anchored proteins to the cell wall, and it confirms
      the extracellular proteolytic ability of Cry. neoformans.

PMID- 17233761
TI  - Current status of Kluyveromyces systematics.
AB  - A brief outline of the current taxonomic status of the genus Kluyveromyces is
      presented. Noteworthy are the transfer of several former Kluyveromyces species to
      other genera, the retention of the name Kluyveromyces for K. lactis, K.
      marxianus, and four related species, and some recent attempts to clarify the
      variety status of strains assigned to K. lactis.

PMID- 17233762
TI  - Phytase activity in Cryptococcus laurentii ABO 510.
AB  - Ten Cryptococcus strains were screened for phytase activity, of which the
      Cryptococcus laurentii ABO 510 strain showed the highest level of activity. The
      cell wall-associated enzyme displayed temperature and pH optima of 62 degrees C
      and 5.0, respectively. The enzyme was thermostable at 70 degrees C, with a loss
      of 40% of its original activity after 3 h. The enzyme was active on a broad range
      of substrates, including ATP, D-glucose 6-phosphate, D-fructose 1,6-diphosphate
      and p-nitrophenyl phosphate (p-NPP), but its preferred substrate was phytic acid
      (K(m) of 21 microM). The enzyme activity was completely inhibited by 0.5 mM
      inorganic phosphate or 5 mM phytic acid, and moderately inhibited in the presence
      of Hg(2+), Zn(2+), Cd(2+) and Ca(2+). These characteristics suggest that the Cry.
      laurentii ABO 510 phytase may be considered for application as an animal feed
      additive to assist in the hydrolysis of phytate complexes to improve the
      bioavailability of phosphorus in plant feedstuff.

PMID- 17233763
TI  - The role of FLO11 in Saccharomyces cerevisiae biofilm development in a laboratory
      based flow-cell system.
AB  - A role of the FLO11 in Saccharomyces cerevisiae biofilm development in a flow
      cell system was examined. We carried out an ectopic FLO11 expression in the wild
      type (wt) BY4741 strain that has low levels of endogenous FLO11 transcript. In
      contrast to the nonadhesive wt, the FLO11 overexpression strain (BY4741 FLO11(+))
      readily adhered to both liquid-hydrophobic and liquid-hydrophilic solid
      interfaces and was able to grow as a biofilm monolayer in a flow system. Cellular
      features associated with FLO11 were examined and found to be consistent with the
      previous studies conducted in different strains of S. cerevisiae. When grown in
      suspended liquid culture, BY4741 FLO11(+) formed larger cellular aggregates
      (clumps), consisting of from five to 60 cells, and displayed an increased cell
      surface hydrophobicity, without changes in the cell size or growth rate, compared
      to wt. However, the invasive growth associated with FLO11 expression was not
      observed in BY4741 FLO11(+). The significance of these findings is discussed in
      the context of clinically and industrially relevant biofilms.

PMID- 17233764
TI  - An atypical active cell death process underlies the fungicidal activity of
      ciclopirox olamine against the yeast Saccharomyces cerevisiae.
AB  - Ciclopirox olamine (CPO), a fungicidal agent widely used in clinical practice,
      induced in Saccharomyces cerevisiae an active cell death (ACD) process
      characterized by changes in nuclear morphology and chromatin condensation
      associated with the appearance of a population in the sub-G(0)/G(1) cell cycle
      phase and an arrest delay in the G(2)/M phases. This ACD was associated neither
      with intracellular reactive oxygen species (ROS) signaling, as revealed by the
      use of different classes of ROS scavengers, nor with a terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL)-positive phenotype.
      Furthermore, CPO-induced cell death seems to be dependent on unknown protease
      activity but independent of the apoptotic regulators Aif1p and Yca1p and of
      autophagic pathways involving Apg5p, Apg8p and Uth1p. Our results show that CPO
      triggers in S. cerevisiae an atypical nonapoptotic, nonautophagic ACD with as yet
      unknown regulators.

PMID- 17233765
TI  - Osmotic shock tolerance and membrane fluidity of cold-adapted Cryptococcus
      flavescens OH 182.9, previously reported as C. nodaensis, a biocontrol agent of
      Fusarium head blight.
AB  - Cryptococcus flavescens (previously reported as C. nodaensis), a biological
      control agent of Fusarium head blight, has been previously shown to have improved
      desiccation tolerance after cold adaptation. The goal of the current study was to
      determine the effect of cold adaptation on the physicochemical properties of C.
      flavescens that may be responsible for its improved desiccation tolerance. The
      results show that cold adaptation improves liquid hyperosmotic shock tolerance
      and alters the temperature dependence of osmotic shock tolerance. Fluorescence
      anisotropy was used to characterize differences in the membrane fluidity of C.
      flavescens with and without cold adaptation. Force curves from atomic force
      microscopy showed a significant increase in the cell wall spring constant after
      cold adaptation. Cold adaptation of C. flavescens during culturing was shown to
      produce smaller cells and produced a trend towards higher CFU yields. These
      results suggest that cold adaptation significantly alters the membrane properties
      of C. flavescens and may be an effective method of improving the desiccation
      tolerance of microorganisms. In addition, we provide information on the correct
      naming of the isolate as C. flavescens.

PMID- 17233766
TI  - Physiology of the yeast Kluyveromyces marxianus during batch and chemostat
      cultures with glucose as the sole carbon source.
AB  - Growth, substrate consumption, metabolite formation, biomass composition and
      respiratory parameters of Kluyveromyces marxianus ATCC 26548 were determined
      during aerobic batch and chemostat cultivations, using mineral medium with
      glucose as the sole carbon source, at 30 degrees C and pH 5.0. Carbon balances
      closed within 95-101% in all experiments. A maximum specific growth rate of 0.56
      h(-1), a biomass yield on glucose of 0.51 g g(-1), and a maximum specific
      consumption of oxygen of 11.1 mmol g(-1) h(-1) were obtained during batch
      cultures. The concentration of excreted metabolites was very low at the culture
      conditions applied, representing 6% of the consumed carbon at most. Acetate and
      pyruvate were excreted to a larger extent than ethanol under the batch
      conditions, and the protein content accounted for 54.6% of the biomass dry
      weight. Steady states were obtained during chemostats at dilution rates of 0.1,
      0.25 and 0.5 h(-1). At the two former dilution rates, cells grew at carbon
      limitation and the biomass yield on glucose was similar to that obtained under
      the batch conditions. Metabolite formation was rather low, accounting for a total
      of 0.005 C-mol C-mol(-1) substrate. At 0.5 h(-1), although the biomass yield on
      glucose was similar to the value obtained under the above-mentioned conditions,
      the cultivation was not under carbon limitation. Under this condition, 2
      oxoglutarate, acetate, pyruvate and ethanol were the prevalent metabolites
      excreted. Total metabolite formation only accounted to 0.056 C-mol C-mol(-1) of
      substrate. A very high protein and a low carbohydrate content (71.9% and 9.6% of
      biomass dry weight, respectively) were measured in cells under this condition. It
      is concluded that K. marxianus aligns with the so-called aerobic-respiring or
      Crabtree-negative yeasts. Furthermore, it has one of the highest growth rates
      among yeasts, and a high capacity of converting sugar into biomass, even when
      carbon is not the limiting nutrient. These results provide useful data regarding
      the future application of K. marxianus in processes aimed at the production of
      biomass-linked compounds, with high yields and productivities.

PMID- 17233767
TI  - Mutations at different sites in members of the Gpr1/Fun34/YaaH protein family
      cause hypersensitivity to acetic acid in Saccharomyces cerevisiae as well as in
      Yarrowia lipolytica.
AB  - The Gpr1 protein of the ascomycetous yeast Yarrowia lipolytica belongs to the
      poorly characterized Gpr1/Fun34/YaaH protein family, members of which have thus
      far only been found in prokaryotes and lower eukaryotes. Trans-dominant mutations
      in the GPR1 gene result in acetic acid sensitivity of cells at low pH. Moreover,
      Gpr1p is subjected to phosphorylation at serine-37 in a carbon source-dependent
      manner. Here we show that several mutations within the ORFs of the GPR1
      orthologues of Saccharomyces cerevisiae, YCR010c (ATO1) and YNR002c (ATO2), also
      trans-dominantly induce acetic acid hypersensitivity in this yeast. We
      demonstrate that the C-termini of mutated Gpr1p, Ycr010cp and Ynr002cp are
      necessary for the triggering of acetic acid sensitivity. Phosphorylation of Y.
      lipolytica Gpr1p was also affected by several mutations. Data further suggest
      that Gpr1p exists in an oligomeric state.

PMID- 17233768
TI  - Debaryomyces singareniensis sp. nov., a novel yeast species isolated from a coal
      mine soil in India.
AB  - Three strains (AP19, AP19-4 and AP19-6) of a novel yeast species were isolated
      from soil from the Singareni coal mines, Andhra Pradesh, India. They were
      morphologically, physiologically and phylogenetically identical and produced one
      to four spherical ascospores per ascus. Phylogenetic analysis using the D1/D2
      variable domain of the large-subunit rRNA gene indicated that the closest
      relative of these strains is Debaryomyces etchellsii (2.6% divergence). Other
      species related to these strains are D. mycophilus (5.1% divergence) and species
      of the D. hansenii cluster (4.9-5.6% divergence). The novel species differs by 20
      and 15 physiological tests from D. etchellsii and D. mycophilus, respectively.
      Phylogenetic analysis of the internal transcribed spacer (ITS) region also
      indicated that strains of the new species are related to D. etchellsii (7.7%
      divergence), followed by species of the D. hansenii cluster (9-10% divergence).
      In the small-subunit rRNA gene sequences, they differed from D. etchellsii by
      seven substitutions and one insertion or deletion of a base in a sequence (indel)
      and from D. mycophilus by 17 substitutions and 1 indel. The physiological,
      biochemical and molecular data suggest that these strains belong to a novel
      species, for which we propose the name Debaryomyces singareniensis sp. nov. The
      type strain of AP19(T) (=MTCC 7061(T)=CBS 10405(T)). The Mycobank number of the
      new species is MB510046.

PMID- 17233769
TI  - Genetic diversity of Dekkera bruxellensis yeasts isolated from Australian
      wineries.
AB  - Yeasts of the genus Dekkera and its anamorph Brettanomyces represent a
      significant spoilage issue for the global wine industry. Despite this, there is
      limited knowledge of genetic diversity and strain distribution within wine and
      winery-related environments. In this study, amplified fragment length
      polymorphism (AFLP) analysis was conducted on 244 Dekkera bruxellensis isolates
      from red wine made in 31 winemaking regions of Australia. The results indicated
      there were eight genotypes among the isolates, and three of these were commonly
      found across multiple winemaking regions. Analysis of 26S rRNA gene sequences
      provided further evidence of three common, conserved groups, whereas a phylogeny
      based upon the AFLP data demonstrated that the most common D. bruxellensis
      genotype (I) in Australian red wine was highly divergent from the D. bruxellensis
      type strain (CBS 74).

PMID- 17233770
TI  - Technetium-99m sestamibi scintigraphy is sensitive and specific for the staging
      and the follow-up of patients with multiple myeloma: a multicentre study on 397
      scans.
AB  - We evaluated the additional benefit of Technetium(99)-sestamibi (99mTc-MIBI)
      scanning in comparison with standard X-ray techniques for multiple myeloma
      patients either at diagnosis or during follow-up. Between February 2001 and
      January 2005, 397 whole body scans were acquired. On 229 scans performed at
      diagnosis, 146 (64%) were positive and 81 cases have discordant X-ray results.
      The sensitivity of 99mTc-MIBI and X-ray were 77% and 45% respectively. As a
      result of 99mTc-MIBI, 40% of asymptomatic myeloma patients were up-staged. The
      positivity of 99mTc-MIBI correlated significantly with all of the most relevant
      clinical and biological parameters. Multivariate analysis selected only high
      reactive C protein (P = 0.0005), bone marrow infiltration (P = 0.02) and bone
      pain (P = 0.002) as factors affecting 99mTc-MIBI pattern. In 22 patients with
      solitary myeloma, 99mTc-MIBI was positive in 86% of cases and detected more
      disease sites than X-ray. Among 168 scans performed during follow-up, 99mTc-MIBI
      presented high specificity in patients showing a complete response (CR; 86%), and
      correlated with myeloma activity and with response to therapy. At multivariate
      analysis, a positive pattern correlated with bone marrow infiltration (P = 0.002)
      and disease status other than CR (P = 0.03). We conclude that 99mTc-MIBI scanning
      is an additional diagnostic tool with a high specificity for the staging and the
      follow-up of multiple myeloma patients.

PMID- 17233771
TI  - The Journal of Sexual Medicine in 2007: the electronic age.

PMID- 17233772
TI  - Pelvic floor involvement in male and female sexual dysfunction and the role of
      pelvic floor rehabilitation in treatment: a literature review.
AB  - INTRODUCTION: The sphincteric and supportive functions of the pelvic floor are
      fairly well understood, and pelvic floor rehabilitation, a specialized field
      within the scope and practice of physical therapy, has demonstrated effectiveness
      in the treatment of urinary and fecal incontinence. The role of the pelvic floor
      in the promotion of optimal sexual function has not been clearly elucidated. AIM:
      To review the role of the pelvic floor in the promotion of optimal sexual
      function and examine the role of pelvic floor rehabilitation in treating sexual
      dysfunction. MAIN OUTCOME MEASURE: Review of peer-reviewed literature. RESULTS:
      It has been proposed that the pelvic floor muscles are active in both male and
      female genital arousal and orgasm, and that pelvic floor muscle hypotonus may
      impact negatively on these phases of function. Hypertonus of the pelvic floor is
      a significant component of sexual pain disorders in women and men. Furthermore,
      conditions related to pelvic floor dysfunction, such as pelvic pain, pelvic organ
      prolapse, and lower urinary tract symptoms, are correlated with sexual
      dysfunction. CONCLUSIONS: The involvement of the pelvic floor in sexual function
      and dysfunction is examined, as well as the potential role of pelvic floor
      rehabilitation in treatment. Further research validating physical therapy
      intervention is necessary.

PMID- 17233773
TI  - Oxytocin involvement in SSRI-induced delayed ejaculation: a review of animal
      studies.
AB  - INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) differ in the
      severity of induced ejaculation delay. Various studies indicate that oxytocin is
      involved in sexual behavior. AIM: To review and evaluate the involvement of
      oxytocin in SSRI-induced ejaculation delay. MAIN OUTCOME MEASURES: Oxytocine
      release, 5-hydroxytryptamine (5-HT) neurotransmission, and desensitization of 5
      HT(1A) receptors. METHODS: A review and critical analysis of animal studies
      investigating the interaction of serotonergic and oxytocinergic neurotransmission
      in relation to the ejaculation process. RESULTS: Although acute treatment with
      the SSRIs fluoxetine and paroxetine immediately causes increased serotonin
      levels, delayed ejaculation does not occur. The increased serotonin levels induce
      oxytocin release via activation of 5-HT(1A) receptors, and this might compensate
      for the inhibitory actions of serotonin on sexual behavior. Chronic treatment
      with fluoxetine and paroxetine desensitizes 5-HT(1A) receptors on oxytocin
      neurons, and that might in part determine the onset of delayed ejaculation.
      Desensitization of 5-HT(1A) receptors is less strong following chronic treatment
      with the SSRIs fluvoxamine or citalopram, which may attenuate the degree of
      delayed ejaculation. CONCLUSIONS: Preliminary data suggest that the severity of
      chronic SSRI treatment-induced delayed ejaculation and the differences between
      the various SSRIs in inducing ejaculation delay is related to gradual
      desensitization of 5-HT(1A) receptors on oxytocin neurons.

PMID- 17233774
TI  - Sexual counseling for women in the context of physical diseases: a teaching model
      for physicians.
AB  - INTRODUCTION: Chronic medical conditions are frequently associated with sexual
      difficulties and problems, which are often underreported and underdiagnosed.
      Patients may feel that sexual problems in the context of disease are not
      important enough to be mentioned to their physicians, and physicians may feel
      uncomfortable and sometimes incompetent. Furthermore, the diagnostic criteria of
      Diagnostic and Statistical Manual of Mental Disorders-IV and International
      Classification of Diseases-10 are focused on the phenomenology of the sexual
      response without any specificity regarding diseases. AIM: To facilitate access
      for patients and physicians, we wanted to develop a tool for assessment and
      discussion of sexual problems in the context of disease. This tool should be
      broadly applicable, easy to use and learn for nonmental health professionals.
      MAIN OUTCOME MEASURES: Content analysis with respect to the integration of
      general sexological and disease-specific dimensions. Formulation of a diagnostic
      and therapeutic algorithm that can be used as a teaching tool. METHODS: Based on
      our experience as a liaison-consultation sexological division of the university
      hospital of Basel, we analyzed the sexological diagnostic workup performed with
      the following group of female patients: women with benign gynecologic conditions;
      women with incontinence; oncological patients (mammary carcinoma, genital
      carcinoma); neurological patients (multiple sclerosis, spine injury,
      Parkinson's); patients with metabolic and endocrine disorders (diabetes,
      metabolic syndrome, polycystic ovarian syndrome); and patients with mental health
      disorders (depression, anxiety disorder, schizophrenia). We extracted the
      commonly used steps in the workup to construct a tool with easy-to-remember
      elements, which would help the physician to evaluate patients' sexual problems
      and plan for referral or therapy. RESULTS: We could differentiate three
      diagnostic dimensions. The first were person-related preexisting factors, such as
      sexual satisfaction and function, age, body image, and general well-being. The
      second were the disease-specific implications, which could be summarized under
      the 8 Ds: Danger, Destruction, Disfigurement, Disability and pain, Dysfunction,
      Dysregulation, Disease load, and Drugs. The third was the patient's and partner's
      general response to the disease determined by affective response, coping style,
      body image impact, and changes in relationship dynamics. CONCLUSION: Sexual
      problems are frequent in many clinical conditions, but are not yet a routine part
      of diagnostic workup and therapeutic planning. We have developed a tool to help
      physicians in different clinical settings to evaluate sexual problems of the
      female patients with specific clinical conditions in order to facilitate access
      to recognition and possible treatment.

PMID- 17233775
TI  - Sexual desire in a nationally representative Danish population.
AB  - INTRODUCTION: There are only a few studies on the frequency of sexual desire in
      the general population, whereas studies investigating the frequency of disordered
      sexual desire are more common. AIM: The aim of this study was to describe the
      frequency of sexual desire in a representative sample of the adult Danish
      population and to analyze the relationships between a number of relevant
      variables and sexual desire. METHODS: The study population (N = 10,458, response
      rate 84.8%) answered a questionnaire with questions on sexual matters. The
      representativity of the population was examined. The frequency of self-reported
      sexual desire and decrease in sexual desire over a 5-year period was calculated
      for the two genders across age cohorts. Multiple logistic regression analysis was
      used to analyze the relationship between potential determinants and sexual
      desire. MAIN OUTCOME MEASURES: The frequency of self-reported sexual desire and
      decrease in sexual desire was examined. Factors of importance for sexual desire
      were tested using two outcome measures: (i) often having sexual desire; and (ii)
      seldom having sexual desire. RESULTS: A significant association between gender
      and sexual desire was found in all age groups, as men had a significantly higher
      level of sexual desire than women. In both genders, the frequency of sexual
      desire was significantly reduced with increasing age. Among the 45- to 66-year
      olds, 57% of the men and 47% of the women reported no change in the level of
      sexual desire over the past 5 years. In general terms, factors related to seldom
      having sexual desire were age and social, psychological, and physical distress in
      both genders. CONCLUSION: This study shows that overall, men have a higher level
      of sexual desire than women; sexual desire decreases with increasing age; and
      social, psychological, or physical distress are associated with low level of
      sexual desire in both genders.

PMID- 17233776
TI  - Study of interstitial cells in the penis: human study.
AB  - INTRODUCTION: Specialized pacemaker cells, similar to the interstitial cells of
      Cajal (ICC) of the gut, have been detected in the urinary organs and are thought
      to pace their motile activity. AIM: We investigated the hypothesis that such
      cells could also exist in the corpora cavernosa (CC) of the human penis. METHODS:
      During the treatment of Peyronie's disease in 11 subjects (age 42.6 +/- 3.2 SD
      years), 3 x 3 mm strips were excised from each of the two CC and subjected to C
      kit immunohistochemistry. Controls for the specificity of the antisera consisted
      of incubation of the tissue with normal rabbit serum substituted for the primary
      antiserum. MAIN OUTCOME MEASURES: Interstitial cells similar to ICC could exist
      in the CC based on C-kit immunohistochemistry. RESULTS: C-kit positive branched
      interstitial cells were detected in the CC. They were clearly distinguishable
      from the smooth muscle cells that were C-kit negative and non-branched. Although
      the mast cells were C-kit positive, they had a smooth body surface. CONCLUSIONS:
      Interstitial cells have been identified in the CC. They are similar to the ICC
      and may be responsible for initiating the slow waves recorded from the smooth
      muscle cells and for controlling their activity. We assume that a deficiency or
      absence of these cells may affect the erectile function of the patient. Further
      studies are needed to explore the role of these cells in erection.

PMID- 17233777
TI  - Quality of erection questionnaire correlates: change in erection quality with
      erectile function, hardness, and psychosocial measures in men treated with
      sildenafil for erectile dysfunction.
AB  - INTRODUCTION: The validated Quality of Erection Questionnaire (QEQ) is a six
      question, patient-reported outcome measure for comprehensively evaluating
      satisfaction with the quality of erections in terms of hardness, onset, and
      duration, which can be used to develop and monitor individualized treatment
      goals. AIMS: To further validate the QEQ by determining
      responsiveness/sensitivity to change in erectile function, erection hardness
      grade, and psychosocial outcomes in men treated with sildenafil for erectile
      dysfunction (ED). METHODS: This open-label, noncomparative, multicenter trial of
      sildenafil (50 or 100 mg as needed for 10 weeks) enrolled men with ED who were in
      a stable, sexual relationship for at least 6 months. Previous phosphodiesterase
      type 5 inhibitor use must have been no more than 6 doses ever and no doses more
      recently than the previous 4 weeks. MAIN OUTCOME MEASURES: The baseline to week
      10 change in the QEQ total score and its correlations with the end-of-treatment
      Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) score and with
      changes in: (i) International Index of Erectile Function (IIEF) domain scores;
      (ii) Self-Esteem And Relationship (SEAR) questionnaire component scores; and
      (iii) the frequency of erections graded hard enough for penetration (grade 3) or
      completely hard (grade 4) on the event log Erectile Hardness Grading Scale.
      RESULTS: The mean +/- standard deviation transformed QEQ total score tripled from
      22.0 +/- 21.1 to 69.9 +/- 35.9 (P < 0.0001), and correlated positively with the
      end-of-treatment EDITS index score (r = 0.71) and with changes in IIEF domain
      scores (r = 0.29-0.86), SEAR component scores (r = 0.37-0.78), and the percentage
      of occasions that grade 3 or 4 erections were achieved (r = 0.66). CONCLUSIONS:
      The brief, easy-to-administer QEQ is responsive to the benefits of sildenafil
      treatment of men for ED and has convergent validity with measures of clinical and
      psychosocial outcomes.

PMID- 17233778
TI  - Thermography as a physiological measure of sexual arousal in both men and women.
AB  - INTRODUCTION: Current physiological measures of sexual arousal are intrusive,
      hard to compare between genders, and quantitatively problematic. AIM: To
      investigate thermal imaging technology as a means of solving these problems.
      METHODS: Twenty-eight healthy men and 30 healthy women viewed a neutral film
      clip, after which they were randomly assigned to view one of three other video
      conditions: (i) neutral (N = 19); (ii) humor (N = 19); and (iii) sexually
      explicit (N = 20). MAIN OUTCOME MEASURES: Genital and thigh temperatures were
      continuously recorded using a TSA ImagIR camera. Subjective measures of sexual
      arousal, humor, and relaxation were assessed using Likert-style questions prior
      to showing the baseline video and following each film. RESULTS: Statistical
      (Tukey HSD) post-hoc comparisons (P < 0.05) demonstrated that both men and women
      viewing the sexually arousing video had significantly greater genital temperature
      (mean = 33.89 degrees C, SD = 1.00) than those in the humor (mean = 32.09 degrees
      C, SD = 0.93) or neutral (mean = 32.13 degrees C, SD = 1.24) conditions. Men and
      women in the erotic condition did not differ from each other in time to peak
      genital temperature (men mean = 664.6 seconds, SD = 164.99; women mean = 743
      seconds, SD = 137.87). Furthermore, genital temperature was significantly and
      highly correlated with subjective ratings of sexual arousal (range r = 0.51-0.68,
      P < 0.001). There were no significant differences in thigh temperature between
      groups. CONCLUSION: Thermal imaging is a promising technology for the assessment
      of physiological sexual arousal in both men and women.

PMID- 17233779
TI  - Do food and dose timing affect the efficacy of sildenafil? A randomized placebo
      controlled study.
AB  - INTRODUCTION: Sildenafil citrate has been used worldwide by men with erectile
      dysfunction. The prescribing information for sildenafil suggests ingestion 1 hour
      before sexual activity and also notes reduced maximum plasma concentration and
      delayed time to maximum concentration following ingestion with a high-fat meal.
      The clinical impact of coingestion of food and these factors has never been
      evaluated. AIM: To determine, using a naturalistic study design, whether
      sildenafil taken 1 hour before or during a meal compared with usual ingestion 30
      60 minutes before sexual activity affects efficacy or patient satisfaction.
      METHODS: After a 1-2-week washout, 48 men (29-79 years old), currently satisfied
      with sildenafil, followed each of four regimens: (A) sildenafil 1 hour before a
      meal and placebo 30-60 minutes before planned coitus vs. (B) placebo 1 hour
      before a meal and sildenafil 30-60 minutes before coitus; and (C) sildenafil
      during a meal and placebo 30-60 minutes before coitus vs. (D) placebo during a
      meal and sildenafil 30-60 minutes before coitus. Subjects were not instructed to
      change their regular dietary habits during the course of the study. MAIN OUTCOME
      MEASURES: Change from baseline in the International Index of Erectile Function
      (IIEF) Erectile Function (EF) domain score, responses to Sexual Encounter Profile
      (SEP) questions 2 (erection sufficient for penetration) and 3 (erection
      sufficient to complete intercourse), and measures of patient preference and
      satisfaction. RESULTS: Mean changes in IIEF-EF domain scores were 11.4 for
      regimens A and B and 11.2 for C and D. Positive SEP2 responses were recorded for
      93.9% and 91.8% of intercourse attempts in A and B and 91.4% and 92.6% in C and
      D. Corresponding results for SEP3 were 84.7% and 85.9%, and 83.4% and 87.5%,
      respectively. There were no significant differences between pairs of treatments
      on satisfaction. The time between sildenafil ingestion and intercourse attempt (0
      0.5 to >10 hours) had no significant effect on responses to SEP2, but decreased
      responses to SEP3 from a maximum of 92.8% at 1.5-2 hours to 81.6% at more than 10
      hours (P = 0.003). CONCLUSIONS: No significant loss of efficacy occurs when
      sildenafil is taken shortly before or with a meal. The duration of action for
      sildenafil may exceed 10 hours.

PMID- 17233780
TI  - Severity of ED: relationship to treatment-seeking and satisfaction with treatment
      using PDE5 inhibitors.
AB  - INTRODUCTION: Research in the past 20 years has demonstrated that erectile
      dysfunction (ED) is an area of concern for men and their partners. AIM: The
      current study was designed to evaluate the impact of the perceived severity of ED
      on treatment-seeking behavior and satisfaction with treatment among men with ED.
      MAIN OUTCOME MEASURES: Participants completed a questionnaire to assess the above
      variables, as well as the duration of ED. METHODS: Participants were 410 men with
      ED who were primarily recruited over the Internet via men's health websites.
      RESULTS: The results demonstrated that men with more severe ED compared with men
      with milder ED were more likely to have discussed their ED with their partner and
      doctor, have sought assistance for their ED problem, but they were also less
      satisfied with the effectiveness of phosphodiesterase type 5 inhibitors, and said
      they were less likely to use them in the future. Men with more severe ED were
      also less likely to want ED medication to last for 24 hours. CONCLUSIONS:
      Implications of these findings for the treatment of men with different levels of
      ED are discussed.

PMID- 17233781
TI  - Vardenafil restores erectile function to normal range in men with erectile
      dysfunction.
AB  - INTRODUCTION: The ability of oral phosphodiesterase type 5 (PDE5) inhibitor
      therapy to restore erectile function to normal is an important attribute to men
      with erectile dysfunction (ED). AIM: To assess the ability of vardenafil to
      restore normal erectile function in men with general ED. METHODS: In two fixed
      dose, parallel-group, double-blind, placebo-controlled, pivotal studies, patients
      received vardenafil (5, 10, or 20 mg) or placebo for 12/26 weeks. MAIN OUTCOME
      MEASURE: In this retrospective analysis, the percentage of patients "returning to
      normal" erectile function at week 12 (as defined by scores > or =26 on erectile
      function domain of International Index of Erectile Function [IIEF-EF]) was
      determined, with further stratification by baseline ED severity, etiology, age,
      and duration of ED. RESULTS: Vardenafil 5, 10, and 20 mg returned 32%, 43%, and
      49% of patients, respectively, to normal erectile function after 12 weeks,
      compared with 10% of patients receiving placebo (P < 0.0001). Return to normal
      IIEF-EF domain scores was noted irrespective of severity, etiology, age, and
      duration of ED, and was observed even in challenging-to-treat subgroups. With
      vardenafil 20 mg, 39% of men with severe ED at baseline, 45-49% of men with ED of
      mixed or organic etiology, 35% of men aged > or =65 years, and 43% of men with ED
      of > or =3 years of duration returned to normal erectile function at week 12.
      Mean per-patient SEP3 (question 3 on the Sexual Encounter Profile) success rates
      in patients achieving IIEF-EF domain scores > or =26 ranged from 87% to 95%.
      CONCLUSION: Vardenafil improves the IIEF-EF domain score to the normal range in a
      substantial proportion of men with ED.

PMID- 17233782
TI  - Efficacy and safety of tadalafil in men with erectile dysfunction with a high
      prevalence of comorbid conditions: results from MOMENTUS: multiple observations
      in men with erectile dysfunction in National Tadalafil Study in the US.
AB  - INTRODUCTION: Limited efficacy and safety data exist from open-label clinical
      trials of phosphodiesterase 5 inhibitors in men with erectile dysfunction (ED)
      and multiple comorbid (MCM) conditions, historically a difficult group to treat.
      AIM: A multicenter study (Multiple Observations in Men with Erectile Dysfunction
      in National Tadalafil Study in the US) assessed efficacy and safety of tadalafil
      in men with ED and MCM conditions. MAIN OUTCOME MEASURES: The primary end point
      was change from baseline in the erectile function (EF) domain of the
      International Index of Erectile Function. Secondary end points included the
      Sexual Encounter Profile, Global Assessment Questions, and Sexual Self-Confidence
      and Spontaneity Domains of the Psychological and Interpersonal Relationship
      Scales. METHODS: This was an open-label, multicenter study in men with ED.
      Tadalafil 20 mg was administered as needed prior to sexual activity, up to
      once/day, for 12 weeks following a 4-week ED-treatment-free period. The MCM group
      was 155 of 1,911 men enrolled in this study. Men in the MCM group met eligibility
      criteria but could not be included in other predefined groups: (i) Caucasian;
      (ii) Black American; (iii) Hispanic (groups 1-3, < or =65 years, no diabetes or
      depression); (iv) depression, < or =65 years, no diabetes; (v) diabetes, < or =65
      years, no depression; (vi) >65 years, no diabetes or depression; and (vii) ED
      subsequent to traumatic spinal cord injury. RESULTS: Mean baseline EF domain
      score in MCM (mean age 65 +/- 9 years) was 12.2 +/- 6.5; 52% of subjects had
      severe ED; 72% diabetes mellitus; 67% cardiovascular disease (including
      hypertension); 49% hyperlipidemia; 38% depression; 84% had two or more
      comorbidities. At end point, there was a significant (P < 0.001) mean change of
      7.6 from baseline in mean EF domain score. Among men with severe ED, 22% achieved
      an EF domain score > or =26. Most common adverse events were headache 5.2%;
      flushing 3.9% and nasal congestion 3.2%; 3% discontinued use because of an
      adverse event. CONCLUSIONS: In this open-label clinical trial of older men with
      ED and MCMs, tadalafil 20 mg significantly increased all efficacy end points and
      was well-tolerated.

PMID- 17233783
TI  - Is sex only for the healthy and wealthy?
AB  - OBJECTIVE: To study reasons for Sildenafil (a phosphodiesterase type 5 inhibitor)
      treatment abortion in erectile dysfunction (ED), with special regard to the
      relation between cost and use. METHODS: Men (N = 132) with ED, where treatment
      with Sildenafil was instituted between 1998 and 2000, were mailed a questionnaire
      in February 2003, regarding their current ED treatment, including frequency of
      use, reasons for change or discontinuation, effect on partner relations, and
      total income of the household. RESULTS: The response rate was 69%. Nearly every
      second man (47%) still used Sildenafil at least twice per month. The remaining
      53% had aborted oral ED treatment: 10% due to return of normal erections, 43% due
      to (either alone or in combination): cost of treatment, impaired health, loss of
      efficacy, change to another ED treatment, or side-effects. Cost was the most
      common cause (48%) for discontinuation. In low-income households, rationing of
      treatment or abortion due to the cost was reported significantly (P < 0001) more
      often (86%) than in high-income households (35%). CONCLUSION: Just under half of
      all the patients (47%) used Sildenafil for more than 2 years after initiation of
      treatment. The cost of the treatment is an important factor for patient
      compliance in households with a low income, despite the fact that the treatment
      is highly effective and improves the partner relationship.

PMID- 17233784
TI  - Corpus cavernosum electromyography with revised methodology: an explorative study
      in patients with erectile dysfunction and men with reported normal erectile
      function.
AB  - INTRODUCTION: A lack of standardization of the recording techniques of corpus
      cavernosum electromyography (CC-EMG) and objective criteria to characterize the
      recorded signals (CC-potentials) are the main difficulties hindering the clinical
      application of this method. These difficulties have been recently overcome by
      revising the recording and interpretation methodology of CC-EMG AIM: To assess if
      CC-EMG performed with the revised methodology is discriminative for well-defined
      clinical conditions in patients with erectile dysfunction (ED). METHODS: Based on
      blinded clinical diagnosis, ED patients were catalogued into five subgroups:
      severe penile fibrosis, cavernous arterial insufficiency (CAI), cardio-vascular
      comorbidity (CVCM) without proven CAI, post-radical retropubic prostatectomy
      (RRP), and psychogenic ED. With four electrodes placed on the penile shaft
      bilaterally, CC-EMG was recorded monopolarly for 30 minutes during flaccidity.
      After evaluation of the recordings by visual inspection, CC-potentials were
      analyzed using cross- and autocorrelation techniques. The parameters evaluated
      were amplitude, duration, dominant frequency (DF), and maximum cross-correlation
      coefficient (Rmax) of CC-potentials recorded from proximal and distal parts of
      the CC. MAIN OUTCOME MEASURES: Comparison of the values of parameters amplitude,
      duration, DF, and Rmax between patient and control groups. RESULTS: A total of
      119 patients with ED and 43 men with reported normal erectile function were
      studied. Thirteen out of 14 patients with severe penile fibrosis did not show any
      distinguishable CC-potential. Patients with CAI had significantly decreased
      amplitude compared with the potent controls, as well as the patients with CVCM
      but without proven CAI. Significantly decreased amplitude and Rmax were detected
      in ED patients following RRP compared with the controls. CONCLUSIONS: Corpus
      cavernosum electromyography performed with the revised methodology is able to
      discriminate ED patients with conditions that are associated with cavernous
      smooth muscle degeneration and/or autonomic neuropathy from men with reported
      normal erectile function.

PMID- 17233785
TI  - Measurement of penile curvature in Peyronie's disease patients: comparison of
      three methods.
AB  - AIM: Peyronie's disease (PD) may be treated in a medical or surgical fashion.
      Factors involved in the decision of which treatment to choose include duration of
      disease and magnitude of penile deformity. Curvature can be measured using at
      home photography (AHP), vacuum erection device (VED), or intracavernosal
      injection (ICI). This study was undertaken to determine the concordance between
      the three methods of deformity assessment. Patients were also questioned
      regarding the presence of erectile dysfunction (ED) based on self-report and the
      International Index of Erectile Function. MATERIALS AND METHODS: A total of 68
      men presented to their urologist after taking penile photographs from three
      angles during maximal erectile rigidity. In the office, a VED was used to induce
      erection, and a goniometer was utilized to measure degree of curvature. ICI with
      trimix was then used to induce artificial erection, which was measured with a
      goniometer as well. RESULTS: There was a statistically significant difference in
      self-report curvature magnitude compared with measured ICI-assisted curvature.
      Curvature profiles included dorsal plaques in 50 patients (73.5%), ventral
      plaques in 10 (15%), and lateral in eight (11%). Using ICI, the mean curvature
      measured was 42 degrees. Mean degree of curvature using VED was 33 degrees, while
      that of photography was 34 degrees. Photographic measurements differed most from
      ICI in men with concurrent ED (P < 0.01), while vacuum device measurements were
      most inaccurate in men with curvatures of >60 degrees. CONCLUSIONS: Our results
      show that the degree of curvature measured using vacuum-assisted device and AHP
      is underestimated as compared with the gold standard ICI. We therefore recommend
      that ICI be used to most accurately determine degree of deformity. If ICI is not
      available, it is imperative that the same manner of measurement be used between
      all patients in a study group, as well as during serial evaluation in a trial.

PMID- 17233786
TI  - Transdermal testosterone gel prn application for hypoactive sexual desire
      disorder in premenopausal women: a controlled pilot study of the effects on the
      arizona sexual experiences scale for females and sexual function questionnaire.
AB  - INTRODUCTION: Several studies suggest that increased plasma testosterone can
      improve sexual function and desire in post-oophorectomy or postmenopausal women.
      However, side effects of chronic daily testosterone raise questions about the
      generalizability of this treatment approach. Sublingual testosterone was reported
      to cause testosterone levels to peak after 15 minutes and then decline to
      baseline levels within 90 minutes. Three to 4 hours after reaching testosterone
      peak, increased genital sensations and sexual lust were reported. AIM: We
      hypothesized that a single dose of testosterone given 4-8 hours prior to planned
      intercourse in women with hypoactive sexual desire disorder (HSDD) might increase
      desire without side effects associated with chronic use. METHODS: The design was
      randomized double-blind crossover. Premenstrual women with HSDD received eight
      packets of gel or identical placebo for use before intercourse twice weekly for 1
      month. For a second month, the alternate treatment was given. MAIN OUTCOME
      MEASURES: Ratings were performed using the patient-rated Arizona Sexual
      Experiences Scale for females and the clinician-rated Sexual Function
      Questionnaire (SFQ-V1). RESULTS: Ten patients completed the study. On the five
      item self-report Arizona, the item "How easily are you aroused?" was
      significantly improved on testosterone gel vs. placebo, P = 0.03. There were
      similar trends on the physician-rated SFQ-V1 "arousal-sensation" cluster.
      CONCLUSIONS: These preliminary results suggest that testosterone gel given prn
      before intercourse has effects on sexual arousal, and further research is needed
      to define dosage and time schedule to optimize this effect and determine its
      clinical relevance.

PMID- 17233787
TI  - Genital and subjective measurement of the time course effects of an acute dose of
      testosterone vs. placebo in postmenopausal women.
AB  - INTRODUCTION: Recent research on the impact of testosterone (T) on female sexual
      function has yielded inconsistent results, and few studies have used
      physiological measures of genital arousal. AIM: This study examined the effects
      of an acute dose of methyltestosterone (MT) on physiological (genital) and
      subjective sexual response in postmenopausal women. MAIN OUTCOME MEASURES:
      Vaginal pulse amplitude (VPA) and self-reported sexual response. METHODS:
      Randomized, double-blind, crossover, placebo-controlled trial of 5 mg MT,
      consisting of two separate 8-hour visits. Participants were 10 postmenopausal
      women without sexual dysfunction. Participants viewed both neutral and erotic
      video segments during five post-dose trials while their genital and subjective
      responses were monitored. RESULTS: The Wilcoxon signed rank test indicated a
      significant difference in VPA between the T (M = 0.018, SD = 0.018) and placebo
      (M = 0.016, SD = 0.017) conditions at 4.5 hours post-dose (P = 0.03). Higher
      difference scores were noted for 80% of subjects during the T condition at 4.5
      hours, in contrast with only 50% of subjects responding to T at the other four
      time points. No differences were found on VPA relative change scores or
      subjective sexual arousal scores. When summed across all five time points,
      genital and subjective measures were correlated regardless of medication
      condition (0.62 and 0.60 for self-reported physical and mental sexual arousal
      scores, respectively). CONCLUSIONS: These findings in postmenopausal women
      combined with those of two previous investigations in premenopausal women
      demonstrate a probable acute-dose time delay for genital sexual effects of
      exogenous T with no change in self-reported sexual arousal. Further investigation
      is needed to determine whether acute dosing of T has a consistent and predictable
      impact on genital arousal that has promise for the treatment of any subgroup of
      women with sexual disorders.

PMID- 17233788
TI  - Surgical techniques: modeling technique for penile curvature.

PMID- 17233791
TI  - Sexual dysfunctions: classifications and definitions.
AB  - Sexual classification systems are based on precise and understandable definitions
      of sexual dysfunctions and are needed for investigative research, determination
      of diagnostic standards, and delineation of treatment strategies. The four major
      categories of sexual dysfunctions include disorders of sexual desire/interest,
      arousal, orgasm, and sexual pain. The purpose of this article is to review the
      major features, differences, and similarities of the six classification systems
      widely used in sexual medicine, including the International Classification of
      Diseases, the Diagnostic and Statistical Manual of Mental Disorders, the National
      Institute of Health Consensus Conference on Impotence, the American Foundation
      for Urologic Diseases, International Consensus Conference on Women's Sexual
      Dysfunction, and the First and Second International Consultations on Sexual
      Dysfunctions.

PMID- 17233792
TI  - The testosterone debate.

PMID- 17233793
TI  - The DSM-IV-TR is an appropriate diagnostic tool for premature ejaculation.

PMID- 17233794
TI  - ROX1, a gene induced by rolB, is involved in procambial cell proliferation and
      xylem differentiation in tobacco stamen.
AB  - The Agrobacterium rhizogenes oncogene rolB mimics the effects of auxin in that it
      increases the sensitivity of transformed cells to this hormone. Here we isolated
      a tobacco gene, ROX1, acting downstream of rolB. We show that plants with reduced
      levels of ROX1 mRNA, due to the expression of a 35S-driven ROX1-antisense
      construct, have flowers with stamens and pistils longer than normal because of an
      increased number of cells. Localized expression of rolB in anthers results in
      overexpression of ROX1 and reduced growth of stamens, due to a reduced number of
      cells. In addition, the longer stamens of antisense plants show a delayed xylem
      differentiation in the lateral bundles, primarily of the junction region between
      anther and filament, while the shorter stamens of ROX1-overexpressing plants show
      a precocious differentiation of xylem cells in the same tissues. Expression of
      ROX1 in stamens peaks at early stages of stamen growth, and ROX1 mRNA is
      localized mostly in anther procambial cells. The sequence of ROX1 shares a
      conserved element with a number of plant genes, including TED3, which is involved
      in xylem differentiation. These results point to a role of ROX1 in the balance
      between proliferation of procambial cells and xylem differentiation during stamen
      development.

PMID- 17233795
TI  - Co-expression of the stress-inducible zinc finger homeodomain ZFHD1 and NAC
      transcription factors enhances expression of the ERD1 gene in Arabidopsis.
AB  - The ZFHD recognition sequence (ZFHDRS) and NAC recognition sequence (NACRS) play
      an important role in the dehydration-inducible expression of the
      Arabidopsisthaliana EARLY RESPONSIVETO DEHYDRATION STRESS 1 (ERD1) gene. Using
      the yeast one-hybrid system, we isolated a cDNA encoding the ZFHD1
      transcriptional activator that specifically binds to the 62 bp promoter region of
      ERD1, which contains the ZFHDRS. Both in vitro and in vivo analyses confirmed
      specific binding of the ZFHD1 to ZFHDRS, and the expression of ZFHD1 was induced
      by drought, high salinity and abscisic acid. The DNA-binding and activation
      domains of ZFHD1 were localized on the C-terminal homeodomain and N-terminal zinc
      finger domain, respectively. Microarray analysis of transgenic plants over
      expressing ZFHD1 revealed that several stress-inducible genes were upregulated in
      the transgenic plants. Transgenic plants exhibited a smaller morphological
      phenotype and had a significant improvement of drought stress tolerance. Using
      the yeast two-hybrid system, we detected an interaction between ZFHD1 and NACRS
      binding NAC proteins. Moreover, co-over-expression of the ZFHD1 and NAC genes
      restored the morphological phenotype of the transgenic plants to a near wild-type
      state and enhanced expression of ERD1 in both Arabidopsis T87 protoplasts and
      transgenic Arabidopsis plants.

PMID- 17233796
TI  - Downregulation of high-isoelectric-point extracellular superoxide dismutase
      mediates alterations in the metabolism of reactive oxygen species and
      developmental disturbances in hybrid aspen.
AB  - Transgenic hybrid aspen (Populus tremula L. x P. tremuloides Michx.) plants
      expressing a high-isoelectric-point superoxide dismutase (hipI-SOD) gene in
      antisense orientation were generated to investigate its function.
      Immunolocalization studies showed the enzyme to be localized extracellularly, in
      the secondary cell wall of xylem vessels and phloem fibers. The antisense lines
      of hipI-SOD exhibited a distinct phenotype; growth rate was reduced, stems were
      thinner and leaves smaller than in wild-type (WT) plants. The abundance of hipI
      SOD was reduced in the bark and xylem of plants from these antisense lines. The
      vascular tissue of transgenic lines became lignified earlier than in WT plants
      and also showed an increased accumulation of reactive oxygen species (ROS). Xylem
      fibers and vessels were shorter and thinner in the transgenic lines than in WT
      plants. The total phenolic content was enhanced in the antisense lines.
      Furthermore, microarray analysis indicated that several enzymes involved in cell
      signaling, lignin biosynthesis and stress responses were upregulated in apical
      vascular tissues of transgenic plants. The upregulation of selected genes
      involved in lignin biosynthesis was also verified by real-time PCR. The results
      suggest that, in the transgenic plants, a premature transition into maturation
      occurs and the process is discussed in terms of the effects of increased
      accumulation of ROS due to reduced expression of hipI-SOD during development and
      differentiation.

PMID- 17233797
TI  - Systematic review of effects of low-moderate prenatal alcohol exposure on
      pregnancy outcome.
AB  - OBJECTIVE: The aim of this study was to review systematically the available
      evidence on studies in humans on the effects of low-moderate levels of prenatal
      alcohol consumption (up to 10.4 UK units or 83 g/week) compared with consumption
      of no alcohol on pregnancy outcome. DESIGN: Systematic review. POPULATION:
      Pregnant women or women who are trying to become pregnant. METHODS: The search
      strategy included Medline, Embase, Cinahl and PsychInfo for the years 1970-2005.
      Titles and abstracts were read by two researchers and inclusion/exclusion being
      decided according to prespecified criteria. All the included articles were then
      obtained and read in full by the two researchers to decide on inclusion. The
      articles were assessed for quality using the Newcastle-Ottawa Quality Assessment
      Scales. MAIN OUTCOME MEASURES: Outcomes considered were miscarriage, stillbirth,
      intrauterine growth restriction, prematurity, birthweight, small for gestational
      age at birth and birth defects including fetal alcohol syndrome. RESULTS: The
      search resulted in 3630 titles and abstracts, which were narrowed down to 46
      relevant articles. At low-moderate levels of consumption, there were no
      consistently significant effects of alcohol on any of the outcomes considered.
      Many of the reported studies had methodological weaknesses. CONCLUSIONS: This
      systematic review found no convincing evidence of adverse effects of prenatal
      alcohol exposure at low-moderate levels of exposure. However, weaknesses in the
      evidence preclude the conclusion that drinking at these levels during pregnancy
      is safe.

PMID- 17233798
TI  - Is the use of parasympathomimetics for treating an underactive urinary bladder
      evidence-based?
AB  - An underactive urinary bladder (UUB), often occurring after surgery, can lead to
      urinary retention even in otherwise healthy people. We systematically reviewed
      published reports to determine whether the use of parasympathomimetic agents is
      warranted in patients with a UUB. Agents allegedly useful in treating UUB were
      identified from urology and pharmacology textbooks. A systematic search for
      randomized clinical trials in patients with UUB using these agents revealed 10
      such studies. Controls typically received placebo or no treatment. While three
      studies reported statistically significant improvements relative to the control
      group, six did not and one even reported a significant worsening of symptoms.
      There was no evidence for differences between individual drugs, specific uses of
      such drugs, or in outcome measures. We conclude that the available studies do not
      support the use of parasympathomimetics for treating UUB, specifically when
      frequent and/or serious possible side-effects are taken into account.

PMID- 17233799
TI  - Fluoroquinolone use is the predominant risk factor for the development of a new
      strain of clostridium difficile-associated disease.

PMID- 17233800
TI  - The incidence of high-grade prostatic intraepithelial neoplasia and atypical
      glands suspicious for carcinoma on first-time saturation needle biopsy, and the
      subsequent risk of cancer.
AB  - OBJECTIVE: To investigate the detection rate and extent of high-grade prostatic
      intraepithelial neoplasia (HGPIN) and atypical glands (AG) suspicious for
      prostate cancer, and the cancer risk in subsequent biopsies, diagnosed by a first
      24-core saturation biopsy, as although the optimum extent of biopsy is
      controversial there is a trend to increase the number of cores taken, and apart
      from detecting prostate cancer, identifying HGPIN and AG is associated with a
      greater risk of finding cancer in subsequent biopsies, thus warranting a closer
      follow-up. PATIENTS AND METHODS: The study included 100 men with consecutive
      first-time saturation biopsies; the indications for biopsy were an abnormal
      digital rectal examination and/or a serum prostate-specific antigen (PSA) level
      of >2.5 ng/mL. Each biopsy specimen was reviewed retrospectively by two
      pathologists to confirm the histological diagnosis. The number and percentage of
      cores positive for HGPIN, bilateral involvement and multifocality (HGPIN
      involving two or more cores) were recorded in each case. The presence of AG and
      cancer was also recorded. An extended (10-12 cores) repeat biopsy was available
      in 23 patients. RESULTS: The median (range) age and PSA level of the patients was
      63 (41-80) years and 4.9 (1.5-67.0) ng/mL, respectively. Of the 100 patients, 34%
      had normal findings (benign prostatic tissue, BPT), 39% had cancer, 26% had HGPIN
      and cancer, 22% had HGPIN alone, and 5% had AG. Repeat biopsies were available in
      nine of the 22 (41%) patients with HGPIN, four of five with AG, and 10 of the 34
      (29%) with BPT. The median (range) interval between the first and second biopsy
      was 13 (4-36) months. Prostate cancer was detected at the second biopsy in a
      third of patients with isolated HGPIN on the first biopsy, and one of the four
      with AG. None of the patients with BPT had cancer on re-biopsy. The cancer
      detection rate was significantly greater in patients with multifocal than in
      those with unifocal HGPIN (80% vs none, P = 0.010). The median number of cores
      and percentage of tissue involved by HGPIN was 3.5 (2-5) and 1.0 (0.5-1.2)%,
      respectively, in patients with cancer detected in repeat biopsies, compared to
      1.0 (1-3) and 0.2 (0.2-0.6)% in patients without cancer on repeat biopsy (P =
      0.023 and 0.015, respectively). CONCLUSION: Identifying multifocal HGPIN on first
      saturation biopsy is associated with an overall cancer detection rate of 80% on
      repeat 10-12-core biopsy. Although there were few patients, the detection of
      multifocal HGPIN warrants additional searches for concurrent invasive carcinoma
      by repeated biopsy.

PMID- 17233801
TI  - Dynamic dose-feedback prostate brachytherapy in patients with large prostates
      and/or planned transurethral surgery before implantation.
AB  - OBJECTIVE: To compare the quality of permanent prostate brachytherapy (PPB)
      implants, dosimetric outcomes and urinary morbidity between patients with large
      (>50 mL) and those with smaller prostates, treated with a dynamic dose-feedback
      technique as monotherapy for localized prostate cancer. PATIENTS AND METHODS: The
      series included patients with pre-existing bladder outlet obstruction managed
      with planned transurethral resection or incision of the prostate; 155 consecutive
      men had PPB implants as monotherapy for localized prostate cancer using a dynamic
      dose-feedback approach. Dosimetric variables assessed included the implant
      volume, the minimum dose to 90% of the prostate (D90), and the volumes of
      prostate receiving 100% and 150% of the prescribed dose as a percentage of the
      total volume (V100 and V150), during and after implantation. Urinary morbidity
      was recorded in terms of acute urinary retention (AUR), the need for surgical
      intervention after implantation and the American Urologic Association (AUA)
      symptom score at baseline, 1.5, 3, 6, 9, 12 and 18 months. RESULTS: In all, 38
      patients had prostate volumes of >or=50 mL; prostate volume had no influence on
      any dosimetric variable assessed. Two patients with large prostates (>or=50 mL)
      had AUR and required delayed surgery. Three patients with small prostates (<50
      mL) had transient retention; the differences were not statistically significant
      (Fisher's exact test). AUA symptom scores peaked at 6 weeks and returned to
      baseline within a year; there were no statistically significant differences
      between the groups. Eight patients had planned transurethral surgery at >or=4
      months before implantation; they all had D90s of >130 Gy and had no incontinence.
      CONCLUSION: Using the dynamic feedback technique, there was no adverse dosimetric
      and urinary morbidity in men having PPB and with prostates of >50 mL. Likewise,
      there were no impediments, e.g. pubic arch interference, which precluded a
      favourable dosimetric implant in men with a large prostate. Large prostates
      should not be a contraindication to PPB and require no hormonal cytoreduction.
      Patients with obstructive lower urinary tract symptoms can be managed with
      planned transurethral prostatic surgery before implantation, without compromising
      implant quality or morbidity.

PMID- 17233802
TI  - A prospective evaluation of the impact of scheduled follow-up appointments with
      compliance rates after vasectomy.
AB  - OBJECTIVE: To prospectively determine the impact of scheduled follow-up
      appointments with compliance rates after vasectomy. PATIENT AND METHODS: During a
      study period of 18 months, 228 consecutive men had a vasectomy, of whom 114 were
      instructed to bring a semen sample to the office and 114 were given a follow-up
      appointment to submit samples. All men were instructed to submit specimens at 2
      months after vasectomy and at 1-month intervals until two consecutive samples
      were azoospermic. The mean (range) follow-up was 16 (6-24) months. Compliance
      rates for the appointment and no-appointment group were compared using a two
      sided Fisher's exact test. A subgroup analysis used a logistic regression model.
      RESULTS: In the appointment group, 96/114 (84%) of patients complied with
      instructions to bring the first sample at 2 months, and in the no-appointment
      group, 74/114 (65%) complied (P=0.001). In the appointment group, 43/114 (48%) of
      patients complied with instructions to provide two consecutive azoospermic
      specimens and in the no-appointment group, 23/114 (20%) complied (P=0.005). A
      subgroup analysis of patients who provided a sample at 2 months indicated that,
      on adjusting for the results of the first test, patients with appointments were
      1.17 times more likely to provide additional specimens than patients with no
      appointments. Adjusting for the type of appointment, patients who had sperm
      present in the first test were 6.72 times more likely to provide additional
      specimens than patients who were azoospermic on the first test. CONCLUSION:
      Scheduling an appointment after vasectomy provides a statistically and clinically
      significant improvement in compliance.

PMID- 17233803
TI  - Clinically localised prostate cancer is microsatellite stable.
AB  - OBJECTIVES: To determine the frequency of microsatellite instability (MSI) change
      with mono-, di- and tetranucleotide markers in clinically localized prostate
      cancer, and to correlate those markers with clinical and pathological variables.
      MATERIALS AND METHODS: Two forms of MSI have been described in human cancer: MSI
      typical of hereditary nonpolyposis colon cancer, defined with mono- and
      dinucleotide repeat MS; and a second variety of MSI is best seen at selective
      tetranucleotide repeats, i.e. elevated microsatellite alterations at select
      tetranucleotides (EMAST). Prostate specimens were taken from 50 patients. The MS
      analysis used the Bethesda consensus panel (BCP) and four tetranucleotide loci
      shown to detect the presence of EMAST. RESULTS: All but four tumours were stable
      for the 14 loci investigated. There were two (4%) cases with adenomatous
      polyposis coli (APC) instability among the BCP markers and the same instability
      rate (4%) amongst the EMAST markers. These four tumours were all unstable at one
      locus of the 10 markers of the BCP that classified them as MS stable.
      CONCLUSIONS: The MSI related to a mismatch repair deficiency or to the EMAST does
      not seem to be important in prostate cancer in the early stages of the disease.

PMID- 17233804
TI  - Side-effects of treatment for localized prostate cancer: are they valued
      differently by patients and healthy controls?
AB  - OBJECTIVES: To determine how men treated for localized prostate cancer and who
      had permanent side-effects, and healthy controls, would value five descriptions
      of health states associated with side-effects of treatment for localized prostate
      cancer, hypothesising that patients would value the health states as less
      detrimental than men with no prostate cancer. PATIENTS, SUBJECTS AND METHODS: In
      previous research, patients with prostate cancer reported high generic quality-of
      life scores after primary treatment, despite side-effects; it was suggested that
      these patients accepted the side-effects, i.e. urinary, bowel and sexual
      dysfunction, as 'part of the bargain' because they felt they were saved from a
      life-threatening disease. Thus, we asked 54 men who had been treated for
      localized prostate cancer and had permanent side-effects, and 53 healthy
      controls, to value five descriptions of health states. All respondents valued all
      descriptions using two valuation methods, a visual analogue scale (VAS, range 0
      100) and time trade-off (TTO, range 0-1). The respondent functioning was assessed
      using the EuroQol-5D, completed with items on urinary, bowel and sexual function.
      RESULTS: Patients and healthy controls had similar valuations for nine of the 10
      comparisons (five health states by two methods). Valuations in both groups
      resulted in the same ranking order of states on the TTO and one exchange in rank
      order on the VAS. CONCLUSIONS: When asked to value five health states associated
      with side-effects of treatment for localized prostate cancer, there was no
      difference in the valuation of erectile, urinary and bowel dysfunction between
      patients with permanent side-effects after treatment and healthy controls. More
      likely explanations for the high generic quality-of-life scores after primary
      treatment for prostate cancer are a response shift and insensitivity of generic
      health-related quality-of-life measures.

PMID- 17233805
TI  - Simple enucleation for the treatment of renal angiomyolipoma.
AB  - OBJECTIVES: To report on the role of simple enucleation for treating renal
      angiomyolipoma (AML) in a series of patients treated in our department. PATIENTS
      AND METHODS: We retrospectively reviewed the data of all 37 patients with a
      histopathological diagnosis of renal AML who had either radical nephrectomy
      (three) or nephron-sparing surgery by simple enucleation (34) between January
      1986 and December 2005. Indications for intervention included either symptomatic
      AML or a tumour of >4 cm, regardless to the presence of symptoms or renal masses
      suspicious of malignancy. The patients' status was evaluated last in October
      2006. RESULTS: The mean (sd, median, range) pathological tumour size was 5.2
      (3.4, 4.8, 1.5-15) cm; five patients (15%) were affected by tuberous sclerosis.
      Simple enucleation was successful in all patients but in three (9%) a sharp
      dissection a few millimetres from the tumour was used during critical steps of
      the procedure where it seemed difficult to define the right plane of enucleation.
      Warm ischaemia was used in 79% of patients, with a mean ischaemic time of 11.2
      min. Two patients (6%) required renal hypothermia. A simple parenchymal
      compression was used in five cases (15%). The mean (range) intraoperative blood
      loss was 170 (70-650) mL. None of the patients had postoperative bleeding
      requiring re-intervention but one (3%) required two units of blood after surgery.
      There were no major complications, e.g. prolonged acute tubular necrosis/chronic
      renal insufficiency and urinary leakage/urinoma, but two patients had urosepsis
      not associated with perirenal fluid collection and that required targeted
      antibiotic therapy. At a mean (median, range) follow-up of 56 (50.5, 10-120)
      months none of the patients had local tumour recurrence. Two patients had a small
      AML elsewhere in the operated kidney, detected 18 and 36 months after surgery,
      with a kidney recurrence rate of 6%. CONCLUSIONS: Our data confirm the optimum
      results of simple enucleation for renal AMLs; this technique provides excellent
      long-term local control and no patient had urinary leakage/fistula afterward.

PMID- 17233806
TI  - Relevance of the prostate-specific antigen (PSA) nanotest compared to the
      classical PSA test in the organized mass screening of prostate cancer.
AB  - OBJECTIVE: To assess the reliability of a new measurement of prostate-specific
      antigen (PSA) using a blotting-paper assay (nanotest) compared to the standard
      PSA immunoassay. SUBJECTS AND METHODS: The PSA level was measured in 205 men
      volunteers (median age 70 years, range 41-75) using a nanotest and a standard PSA
      immunoassay, collected at the same time; 30 microL of capillary blood placed on
      to a blotting paper were collected for the nanotest and sent by mail to the same
      laboratory for the two assays. The results were compared statistically using the
      Spearman test, the intraclass correlation coefficient and the Bland-Altman test.
      RESULTS: The nanotest threshold for an abnormal PSA level was 78 pg/mL, which
      corresponded to a standard PSA value of 3 ng/mL, with a sensitivity of 100%.
      There was a significant correlation (r = 0.98, Spearman test; P < 0.001) between
      the nanotest and the standard PSA assay. The intraclass correlation coefficient
      was 0.87. The Bland-Altman test showed a good agreement between the nanotest and
      the standard PSA assay, but there was an increasing proportional difference with
      increasing PSA value. CONCLUSION: There was a very high correlation between the
      nanotest and the standard PSA assay, especially for standard PSA levels of <5
      ng/mL. Economic and clinical studies are indicated to confirm the utility of the
      nanotest in organized mass screening of prostate cancer.

PMID- 17233807
TI  - Bilateral synchronous posterior prone retroperitoneoscopic nephrectomy with
      simultaneous peritoneal dialysis: a new management for end-stage renal disease in
      children.
AB  - OBJECTIVE: To describe a laparoscopic approach for bilateral synchronous
      posterior prone retroperitoneoscopic nephrectomy (BSPPRN) which allows for
      immediate peritoneal dialysis (PD) in children with end-stage renal disease
      (ESRD), as PD is the treatment of choice in these children with ESRD who are
      awaiting renal transplantation. PATIENTS AND METHODS: Traditionally, children
      requiring bilateral native nephrectomy have been managed on haemodialysis before
      being converted to PD at a later stage, but this approach incorporates a
      conventional open transperitoneal nephrectomy, which had associated morbidity.
      Between May 2001 and December 2005, 20 children had BSPPRN with initiation or
      return to PD immediately afterward (mean age at surgery 8.5 years, range 0.5-17).
      The indications for surgery included steroid-resistant proteinuria in 14, drug
      resistant hypertension in four, proteinuria and hypertension in one and
      intractable polyuria in one. BSPPRN used either three or two ports, or the
      'single-instrument port' technique. A PD catheter was placed simultaneously in
      eight children, whilst 10 were already established on PD. RESULTS: BSPPRN was
      successful in 19 children; one developed a peritoneal tear, which necessitated
      conversion to open nephrectomy. The mean (range) operative duration was 160 (110
      180) min. There were no major complications and no child required a blood
      transfusion. PD was established immediately after surgery in 17 children; one had
      a dialysate leak requiring a period of haemodialysis. CONCLUSION: In children who
      require bilateral native nephrectomy before renal transplantation, BSPPRN
      maintains the integrity of the peritoneal cavity, allowing for immediate PD after
      surgery. The technique is safe and has all the added advantages of minimally
      invasive surgery.

PMID- 17233808
TI  - A prospective comparison of transperitoneal and retroperitoneal laparoscopic
      nephrectomy in the extremely obese patient.
AB  - OBJECTIVE: To prospectively compare the outcomes of transperitoneal laparoscopic
      nephrectomy (TLN) and retroperitoneal LN (RLN) in extremely obese patients, as LN
      in such patients (body mass index, BMI >/= 40 kg/m(2)) is an accepted but
      technically challenging undertaking, and either approach to the kidney can be
      used. PATIENTS AND METHODS: Between July 1998 and August 2005, 51 consecutive
      patients with extreme obesity had 53 LNs at our institution (13 TLN and 40 RLN).
      Peri-operative data were collected prospectively in a database approved by the
      Institutional Review Board. RESULTS: There were no statistically significant
      differences between the two approaches for several variables, including baseline
      BMI (44 vs 45; P = 0.23), muscle-splitting extraction incision length (7.0 vs 7.7
      cm; P = 0.53), and intraoperative complications (none vs 5%; P = 0.99). RLN
      tended to cause less estimated blood loss (EBL, 150 vs 100 mL; P = 0.31), a
      shorter operation (190 vs 180 min; P = 0.11), larger specimen weight (682 vs 938
      g; P = 0.078), lower intraoperative open conversion rate (15% vs 0%; P = 0.06),
      and a shorter hospital stay (53.6 vs 37.5 h; P = 0.33), although none of these
      variables was statistically significant at P < 0.05. CONCLUSIONS: In the
      extremely obese patient, RLN tended to have advantages in EBL, operative
      duration, specimen weight, open conversion rate, and duration of hospital stay.
      RLN provides direct access to the renal hilum, and avoids the pannus and
      voluminous intra-abdominal fat encountered during TLN. These data and our
      experience support RLN as the technique of choice for LN in the extremely obese
      patient.

PMID- 17233809
TI  - Modernising urological careers: the 'numbers game'.

PMID- 17233810
TI  - Use of oxidized cellulose for corporal body grafting and suture-less correction
      of severe penile chordee: an experimental study in rabbits.
AB  - OBJECTIVE: To evaluate the efficacy of oxidized cellulose, Surgicel(TM) (Johnson
      & Johnson Medical, New Brunswick, NJ, USA) for patching defects in the tunica
      albuginea in a rabbit model, with a future application to correct chordee.
      MATERIALS AND METHODS: The study comprised nine New Zealand white male rabbits; a
      rectangular 15 x 5-mm defect was created in the ventral tunica albuginea that was
      covered by Surgicel. The skin was closed with no catheters left in situ after the
      procedure. The rabbits were killed in groups of three at 2, 6 and 12 weeks after
      surgery. The evaluation included cavernosography and histopathological
      examination of sections of the penis stained with haematoxylin and eosin, and
      Masson's trichrome. RESULTS: No deaths were caused by the procedure, and none of
      the rabbits developed bleeding or haematoma after surgery. Cavernosography at 2
      weeks showed contrast medium leaking from the site of the Surgicel, but at 6 and
      12 weeks all rabbits had a straight erection with patent corpora and no evidence
      of narrowing or venous leak. Histopathological evaluation revealed evidence of
      the remnants of Surgicel surrounded by acute inflammatory cell infiltrate with
      early neovascularization at 2 weeks. At 6 and 12 weeks, there was complete normal
      regeneration of the tunica albuginea with no foreign-body reaction. CONCLUSIONS:
      In this pilot study, Surgicel had a clear haemostatic effect when covering a
      defect in the tunica albuginea. Moreover, normal tunica albuginea regenerated by
      6 weeks and was maintained at 12 weeks. These results suggest that Surgicel might
      be considered a safe and effective grafting material for tunica albuginea
      substitution, including the surgical management of penile chordee.

PMID- 17233811
TI  - Local interferon-alpha gene therapy elicits systemic immunity in a syngeneic
      pancreatic cancer model in hamster.
AB  - The interferon (IFN) protein is a cytokine with pleiotropic biological functions
      that include induction of apoptosis, inhibition of angiogenesis and
      immunomodulation. We previously examined the two antitumor mechanisms, taking
      advantage of the fact that IFN-alpha did not show cross-species activity in its
      in vivo effect. In a nude mouse subcutaneous xenograft model using human
      pancreatic cancer cells, the expression of human IFN-alpha effectively induced
      cell death of human pancreatic cancer cells, whereas mouse IFN-alpha augmented
      antitumor immunity by stimulation of natural killer cells. Here, we extended our
      investigation to a syngeneic pancreatic cancer model, so that the integrated
      antitumor activity of local IFN-alpha gene therapy, including the
      antiproliferative, proapoptotic, antiangiogeneic and immunomodulatory effects,
      can be evaluated rigorously. When a recombinant hamster IFN-alpha adenovirus was
      injected into syngeneic subcutaneous tumors of hamster pancreatic cancer (PGHAM
      1) cells in Syrian hamster, tumor growth was significantly suppressed due to cell
      death and T cell- and natural killer cell-mediated antitumor immunity. Moreover,
      in this case, tumor regression was observed not only for the injected
      subcutaneous tumors but also for the untreated tumors both in the peritoneal
      cavity and at distant sites. No significant systemic toxicity was observed in the
      treated hamsters. Moreover, the subcutaneous rechallenge of PGHAM-1 cells was
      rejected in three of four cured hamsters from the initial tumor challenge. This
      study further demonstrated that local IFN-alpha gene therapy is a promising
      therapeutic strategy for pancreatic cancer, due to its multiple mechanisms of
      antitumor activity and its lack of significant toxicity.

PMID- 17233812
TI  - MutationView/KMcancerDB: a database for cancer gene mutations.
AB  - It is known that cancers are caused by accumulated mutations in various genes and
      consequent functional alterations of proteins that are important for maintenance
      of normal cellular functions. The changes in nucleotide sequences and expression
      patterns of cancer-related genes are being extensively studied to better
      understand the mechanisms of tumorigenesis and to develop methods for DNA/protein
      [corrected] diagnosis and drug discovery. At present, a number of computer
      databases for molecular information on cancer-related genes are available
      publicly through the internet. These databases deal with familial cancer and
      sporadic cancer at the levels of germline mutation or somatic mutation, genomic
      or chromosomal abnormalities, and changes in the expression levels of relevant
      genes. Previously, we constructed a human gene mutation database named
      MutationView (http://mutview.dmb.med.keio.ac.jp/) and have accumulated mutation
      data for approximately 300 genes that are involved mainly in monogenic diseases.
      Forty-two genes are cancer-related and therefore a separate cancer database named
      KMcancerDB was constructed. MutationView/KMcancerDB utilizes a graphic display
      function for both queries and search results much more often than other existing
      databases, making the system quite user friendly. MutationView/KMcancerDB
      provides a highly sophisticated search function for all genes through a single
      internet URL. In the present paper, we briefly review various useful databases
      for cancer-related genes, and describe MutationView/KMcancerDB in more detail.

PMID- 17233813
TI  - The immortalized cell lines with differentiation potentials: their establishment
      and possible application.
AB  - Approximately 200 types of the cells are qualified as differentiated cells in the
      human body. If these different types of cells can be separated from each other
      (or cloned) and obtained in sufficient quantity, it will be beneficial for
      studying development, morphogenesis, tissue maintenance, cancer and aging, and
      for reconstructing functional tissues in vitro for regenerative medicine. We
      produced the transgenic mouse and rat harboring SV40 T-antigen gene to make the
      immortalized cell lines in the primary tissue culture and succeeded in
      establishing many functionally active cell lines from various tissues. Many
      immortalized cell lines from various tissues are shown to exhibit the unique
      characteristics of tissue functions and they should be useful as an in vitro
      model of various tissues for physiological and pharmacological investigations.
      Future application of these cells to drug screening is discussed.

PMID- 17233814
TI  - Tumor carbonic anhydrase 9 expression is associated with the presence of lymph
      node metastases in uterine cervical cancer.
AB  - Tumor hypoxia has a pronounced effect on malignant progression and metastatic
      spread of human tumors. As carbonic anhydrases (CA) 9 and 12 are induced by the
      low-oxygen environment within tumors, we investigated the relationship between
      the expression of these two CA and the presence of metastatic lymph nodes (LN) in
      uterine cervical cancer. CA9/CA12 expression was evaluated histochemically in
      primary cervical cancer tissues of 73 patients who underwent laparoscopic LN
      staging and two patients with clinical staging before definitive radiotherapy at
      the National Cancer Center, Korea. We also evaluated CA9 expression in 33
      patients with pathologically confirmed metastatic LN. CA9 expression in the
      primary tumors was significantly associated with LN metastasis (P = 0.03) and
      poorer disease-free survival (relative risk, 6.1; 95% confidence interval, 1.3
      28.3, P = 0.02, multivariate analysis), whereas CA12 expression did not show such
      a relationship. In addition, 21 of 24 metastatic LN revealed similar CA9
      expression (P = 0.001), suggesting that CA9-expressing tumor cells had a higher
      metastatic potential. CA9 was expressed in 45 of 75 (60%) primary tumors, with
      positive tumor cells observed predominantly in the area away from the blood
      vessels. In contrast, CA12 expression was observed in only 29 of 74 primary
      tumors (39%), without a specific pattern. These findings indicate that expression
      of CA9, but not CA12, in tumors is associated with the presence of LN metastases
      and poorer prognosis. Selective application of new treatment modalities based on
      CA9 expression to prevent LN metastases may improve overall treatment outcome in
      patients with uterine cervical cancer.

PMID- 17233815
TI  - Genome-wide array-based comparative genomic hybridization analysis of pancreatic
      adenocarcinoma: identification of genetic indicators that predict patient
      outcome.
AB  - We analyzed the subchromosomal numerical aberrations of 44 surgically resected
      pancreatic adenocarcinomas by array-based comparative genomic hybridization. The
      aberration profile ranged widely between cases, suggesting the presence of
      multiple or complementary mechanisms of evolution in pancreatic cancer, and was
      associated with lymph node metastasis and venous or serosal invasion. A large
      number of small loci, previously uncharacterized in pancreatic cancer, showed non
      random loss or gain. Frequent losses at 1p36, 4p16, 7q36, 9q34, 11p15, 11q13,
      14q32-33, 16p13, 17p11-13, 17q11-25, 18q21-tel, 19p13, 21q22 and 22q11-12, and
      gains at 1q25, 2p16, 2q21-37, 3q25, 5p14, 5q11-13, 7q21, 7p22, 8p22, 8q21-23,
      10q21, 12p13, 13q22, 15q13-22 and 18q11 were identified. Sixteen loci were
      amplified recurrently. We identified novel chromosomal alterations that were
      significantly associated with a range of malignant phenotypes. Gain of LUNX, HCK,
      E2F1 and DNMT3b at 20q11, loss of p73 at 1p36 and gain of PPM1D at 17q23
      independently predicted patient outcome. Expression profiling of amplified genes
      identified Smurf1 and TRRAP at 7q22.1, BCAS1 at 20q13.2-3, and VCL at 10q22.1 as
      potential novel oncogenes. Our results contribute to a complete description of
      genomic structural aberrations and the identification of potential therapeutic
      targets and genetic indicators that predict patient outcome in pancreatic
      adenocarcinoma.

PMID- 17233816
TI  - Nephropathic cystinosis with bone marrow involvement.

PMID- 17233817
TI  - A randomised comparison of melphalan with prednisone or dexamethasone as
      induction therapy and dexamethasone or observation as maintenance therapy in
      multiple myeloma: NCIC CTG MY.7.
AB  - The effectiveness of melphalan plus dexamethasone (M-Dex) with melphalan plus
      prednisone (MP) as induction therapy and dexamethasone with observation as
      maintenance therapy was compared in 585 older patients with multiple myeloma.
      Randomization to the M-Dex arm was stopped as a result of an analysis performed
      which met a predetermined event-related criterion. Of 466 patients randomised to
      MP or M-Dex, no differences were detected in the respective median progression
      free survivals (PFS) [1.8 vs. 1.9 years; Hazard Ratio (HR) = 0.88, 95% CI 0.72
      1.07; P = 0.2] or overall survivals (OS) (2.5 vs. 2.7 years; HR = 0.91, 95% CI
      0.74-1.11; P = 0.3). Of the initial 585 patients, 292 remained evaluable for
      maintenance therapy. Patients randomised to maintenance dexamethasone had a
      superior median PFS (2.8 years vs. 2.1 years; HR = 0.61, 95% CI 0.47-0.79; P =
      0.0002). No difference in median OS was detected (4.1 years vs. 3.8 years; HR =
      0.88, 95% CI 0.65-1.18; P = 0.4). The maintenance therapy results were robust
      when analysed by using two additional methodologies. Dexamethasone did not
      improve clinical outcome when combined with melphalan during induction;
      maintenance dexamethasone improved PFS, but this did not translate into a
      detectable survival advantage.

PMID- 17233818
TI  - Beta1 integrin mediated adhesion increases Bim protein degradation and
      contributes to drug resistance in leukaemia cells.
AB  - It has been shown that the tumour microenvironment confers resistance to
      chemotherapy. Specifically, it was previously reported that adhesion of
      haematopoietic tumour cells to fibronectin (FN) via beta1 integrins confers a
      multi-drug resistance phenotype commonly referred to as cell adhesion mediated
      drug resistance. The present study showed that the pro-apoptotic BCL-2 family
      member Bim was reduced when leukaemia cells were adherent to FN via beta1
      integrins. beta1 integrin-mediated regulation of Bim in K562 cells was
      demonstrated to be partly a result of increased proteasomal-mediated degradation
      of Bim protein levels, and proteasome inhibitors prevent Bim degradation.
      Increased degradation of Bim was not related to activation of the mitogen
      activated protein kinase pathway, as adhesion of K562 cells caused a reduction in
      phospho-extracellular signal-related kinase (ERK)1/2 levels. In addition,
      pharmacological inhibition of MAP/ERK (MEK) with PD98059 did not increase Bim
      levels. Reducing Bim levels by short hairpin RNA targeting inhibited imatinib and
      mitoxantrone-induced cell death. These results showed that beta1 integrin
      mediated adhesion regulates Bim degradation and may contribute to the minimal
      residual disease associated with many haematopoietic malignancies. Together our
      data indicate that disrupting beta1 integrin-mediated regulation of Bim
      degradation may increase the efficacy of drugs, including imatinib, used to treat
      haematopoietic malignancies.

PMID- 17233819
TI  - Dose-adjusted EPOCH plus rituximab is an effective regimen in patients with poor
      prognostic untreated diffuse large B-cell lymphoma: results from a prospective
      observational study.
AB  - This study was designed to assess the efficacy and safety of an infusional DA
      EPOCH (dose-adjusted etoposide/vincristine/doxorubicin/bolus
      cyclophosphamide/prednisone) and rituximab (DA-EPOCH-R) regimen for patients with
      poor prognosis diffuse large B-cell lymphoma (DLBCL). Thirty-three patients, aged
      21-76 years, with an age-adjusted International Prognostic Index (IPI) of 2 or 3,
      were enrolled, and 31/33 patients were evaluable for response. Consolidative
      radiation therapy was given to eight patients with bulky (> or =10 cm) disease at
      presentation. Overall, 26 patients (83.8%) achieved a complete remission (CR),
      four patients (12.9%) achieved a partial remission, and one patient (3.2%) died
      during induction. Two patients relapsed (7.6%) within 15 months. Grade 3-4
      neutropenia developed in 52% of cycles and neutropenic fever in 14% of cycles
      (51% of patients). The estimates for event-free survival (EFS) and overall
      survival at 2 years were 68% and 75% respectively. The only factor related to
      poor EFS was the presence of three age-adjusted IPI-risk factors. We conclude
      that DA-EPOCH-R has clinically significant activity with a favourable toxicity
      profile for poor-prognostic DLBCL patients. The administration of DA-EPOCH-R as
      an outpatient regimen by using a single portable infusion pump may be a feasible
      alternative to improve the compliance and to reduce the total cost of this very
      effective regimen.

PMID- 17233820
TI  - Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute
      T cell lymphoblastic leukaemia with t(11;18)(p15;q12).
AB  - Three NUP98 chimaeras have previously been reported in T cell acute lymphoblastic
      leukaemia (T-ALL): NUP98/ADD3, NUP98/CCDC28A, and NUP98/RAP1GDS1. We report a T
      ALL with t(11;18)(p15;q12) resulting in a novel NUP98 fusion. Fluorescent in situ
      hybridisation showed NUP98 and SET binding protein 1(SETBP1) fusion signals;
      other analyses showed that exon 12 of NUP98 was fused in-frame with exon 5 of
      SETBP1. Nested polymerase chain reaction did not amplify the reciprocal
      SETBP1/NUP98, suggesting that NUP98/SETBP1 transcript is pathogenetically
      important. SETBP1 has previously not been implicated in leukaemias; however, it
      encodes a protein that specifically interacts with SET, fused to NUP214 in a case
      of acute undifferentiated leukaemia.

PMID- 17233821
TI  - Primary nodal marginal zone B-cell lymphoma: clinical features and prognostic
      assessment of a rare disease.
AB  - This study defined the clinical features and assessed the prognosis of 47
      patients (17 males, 30 females, median age 63 years) with primary nodal marginal
      zone B-cell lymphoma. Forty-five per cent had stage IV disease. Hepatitis C virus
      serology was positive in 24%. According to the Follicular Lymphoma International
      Prognostic Index (FLIPI), 33% were classified as low-risk, 34% as intermediate
      risk, and 33% as high-risk. The 5-year overall survival (OS) was 69%. In
      univariate analysis worse OS was associated with: FLIPI (P = 0.02), age > 60
      years (P = 0.05) and raised lactate dehydrogenase (P = 0.05). In multivariate
      analysis, only FLIPI predicted a worse OS (P = 0.02).

PMID- 17233822
TI  - Human Fanconi A cells are susceptible to TRAIL-induced apoptosis.
AB  - Tumour necrosis factor (TNF) contributes to the pathogenesis of bone marrow
      failure in Fanconi anaemia (FA) patients. The sensitivity of haematopoietic cells
      from FA, complementation group A (FANCA) subjects, who represent the majority of
      FA patients, to TNF-related apoptosis-inducing ligand (TRAIL) is unknown. The
      human lymphoblastoid FANCA HSC072 cell line and the genetically corrected
      counterpart HSC072FANCA-neo were tested for apoptoptic response to TRAIL using
      flow cytometry and Western blotting. FANCA cells were more sensitive to TRAIL
      induced apoptosis than their corrected counterparts, indicating that TRAIL
      negatively regulates haematopoietic FANCA cell lines. This effect involved
      poly(ADP-ribose) polymerase-1 cleavage and caspase-8 activation.

PMID- 17233824
TI  - 2B or not 2B? Differential identification of Type 2B, versus pseudo-,von
      Willebrand disease.

PMID- 17233826
TI  - Differential regulation of Escherichia coli topoisomerase I by Fis.
AB  - We previously reported that the P1 promoter of topA encoding topoisomerase I of
      Escherichia coli is activated in response to oxidative stress, in a Fis-dependent
      manner. Here we show that Fis regulation of topA varies with the intracellular
      concentrations of Fis. Thus, when Fis levels are low, hydrogen peroxide treatment
      results in topA activation, whereas at high Fis levels hydrogen peroxide
      treatment renders topA P1 inactive. In vivo DMS footprinting indicates that only
      at low Fis levels, when exposed to the stress, the region of the topA promoter
      changes and P1 becomes active. Potassium permanganate experiments indicate that
      low levels of Fis activate P1 transcription by facilitating the formation of open
      complexes, while high levels of this protein shut off the promoter. DNase I
      footprinting show that Fis binds the promoter region of topA at eight sites with
      different affinities. One low affinity site overlaps the -10, -35 hexamers of RNA
      polymerase. We propose that in response to oxidative stress, when present at low
      levels, Fis binds the promoter region of topA at its high affinity sites, thereby
      facilitating the recruitment of RNA polymerase to P1, while at high levels, Fis
      occupies the low affinity sites as well, and thus prevents the binding of RNA
      polymerase. Our results indicate that the oxidative stress response varies in
      response to changes in growth phase and nutritional environment.

PMID- 17233825
TI  - The trans-envelope Tol-Pal complex is part of the cell division machinery and
      required for proper outer-membrane invagination during cell constriction in E.
      coli.
AB  - Fission of bacterial cells involves the co-ordinated invagination of the envelope
      layers. Invagination of the cytoplasmic membrane (IM) and peptidoglycan (PG)
      layer is likely driven by the septal ring organelle. Invagination of the outer
      membrane (OM) in Gram-negative species is thought to occur passively via its
      tethering to the underlying PG layer with generally distributed PG-binding OM
      (lipo)proteins. The Tol-Pal system is energized by proton motive force and is
      well conserved in Gram-negative bacteria. It consists of five proteins that can
      connect the OM to both the PG and IM layers via protein-PG and protein-protein
      interactions. Although the system is needed to maintain full OM integrity, and
      for class A colicins and filamentous phages to enter cells, its precise role has
      remained unclear. We show that all five components accumulate at constriction
      sites in Escherichia coli and that mutants lacking an intact system suffer
      delayed OM invagination and contain large OM blebs at constriction sites and cell
      poles. We propose that Tol-Pal constitutes a dynamic subcomplex of the division
      apparatus in Gram-negative bacteria that consumes energy to establish transient
      trans-envelope connections at/near the septal ring to draw the OM onto the
      invaginating PG and IM layers during constriction.

PMID- 17233827
TI  - Smooth to rugose phase variation in Vibrio cholerae can be mediated by a single
      nucleotide change that targets c-di-GMP signalling pathway.
AB  - Microorganisms use phase variation to increase population diversity to maximize
      evolutionary success. One such variation is the smooth to rugose phenotype change
      in Vibrio cholerae. We determined that the variation between smooth and rugose
      phenotypes can be controlled by a single nucleotide change in a gene (vpvC)
      predicted to encode a diguanylate cyclase. The vpvC allele found in the rugose
      genetic background is more active at producing c-di-GMP while that in smooth
      genetic background is less active. In support of this finding, disruption of vpvC
      in the rugose genetic variant decreases cellular c-di-GMP levels, diminishes
      rugose-associated phenotypes and yields a smooth variant. Furthermore, the
      frequency of phase variation decreases dramatically when the vpvC locus is
      deleted in the smooth genetic background. Evidence is presented that the rugose
      variant is less susceptible to phage infection than the smooth variant. As phage
      infection is known to control populations of V. cholerae and thus outbreaks of
      cholera, phase variation may increase the evolutionary success of the pathogen.

PMID- 17233828
TI  - Structural basis for operator and antirepressor recognition by Myxococcus xanthus
      CarA repressor.
AB  - Blue light induces carotenogenesis in Myxococcus xanthus. The carB operon encodes
      all but one of the structural genes involved, and its expression is regulated by
      the CarA-CarS repressor-antirepressor pair. In the dark, CarA-operator binding
      represses carB. CarS, produced on illumination, interacts physically with CarA to
      dismantle the CarA-operator complex and activate carB. Both operator and CarS
      bind to the autonomously folded N-terminal domain of CarA, CarA(Nter), which in
      excess represses carB. Here, we report the NMR structure of CarA(Nter), and map
      residues that interact with operator and CarS by NMR chemical shift
      perturbations, and in vivo and in vitro analyses of site-directed mutants. We
      show CarA(Nter) adopts the winged-helix topology of MerR-family DNA-binding
      domains, and conserves the majority of the helix-turn-helix and wing contacts
      with DNA. Tellingly, helix alpha2 in CarA, a key element in operator DNA
      recognition, is also critical for interaction with CarS, implying that the CarA
      CarS protein-protein and the CarA-operator protein-DNA interfaces overlap. Thus,
      binding of CarA to operator and to antirepressor are mutually exclusive, and CarA
      may discern structural features in the acidic CarS protein that resemble operator
      DNA. Repressor inactivation by occluding the DNA-binding region may be a
      recurrent mechanism of action for acidic antirepressors.

PMID- 17233829
TI  - A Ras1-Cdc24 signal transduction pathway mediates thermotolerance in the fungal
      pathogen Cryptococcus neoformans.
AB  - Pathogenic microorganisms must precisely regulate morphogenesis to survive and
      proliferate within an infected host. This regulation is often controlled by
      conserved signal transduction pathways that direct morphological changes in
      varied species. One such pathway, whose components include Ras proteins and the
      PAK kinase Ste20, allows the human fungal pathogen Cryptococcus neoformans to
      grow at high temperature. Previously, we found that Ras1 signalling is required
      for differentiation, thermotolerance and pathogenesis in C. neoformans. We show
      here that the guanine nucleotide exchange factor Cdc24 is a Ras1 effector in C.
      neoformans to mediate the ability of this fungus to grow at high temperature and
      to cause disease. In addition, we provide evidence that the Ras1-Cdc24 signalling
      cascade functions specifically through one of the three Cdc42/Rac1 homologues in
      C. neoformans. In conclusion, our studies illustrate how components of conserved
      signalling cascades can be specialized for different downstream functions, such
      as pathogenesis.

PMID- 17233830
TI  - Transformation in Streptococcus pneumoniae: formation of eclipse complex in a
      coiA mutant implicates CoiA in genetic recombination.
AB  - CoiA is a transient protein expressed specifically during competence and required
      for genetic transformation in Streptococcus pneumoniae, but not for DNA uptake.
      It is widely conserved among Gram-positive bacteria but its function is unknown.
      Here we report that although the rate of DNA uptake was not affected in a coiA
      mutant, the internalized donor DNA did not recombine into the host chromosome to
      form a physical and genetic heteroduplex. Instead, DNA taken up by a coiA mutant
      accumulated in the form of a single-stranded (ss) DNA-protein complex
      indistinguishable from the eclipse complex formed as a recombination intermediate
      in wild-type competent cells. Internalized donor DNA in a dprA mutant did not
      accumulate either as ss DNA or as an eclipse complex. Together, these results
      establish that a coiA mutant exhibits a phenotype different from that of dprA or
      recA mutants, and that CoiA functions at a later step in promoting recombination
      during genetic transformation in Streptococcus pneumoniae.

PMID- 17233831
TI  - Is correction for protein concentration appropriate for protein adduct dosimetry?
      Hypothesis and clues from an aflatoxin B1-exposed population.
AB  - Protein adducts are useful biomarkers for assessing exposure, metabolism and risk
      of carcinogens. Aflatoxin B1-albumin adducts (AAA) and protein carbonyl content
      (PCC) have long been used for assessing aflatoxin exposure and oxidative stress
      to proteins, and the quantitative data are almost exclusively expressed per mg
      protein. Given the large variation in protein concentrations in plasma among
      populations, this may not be the most appropriate method. The objective was to
      test the hypothesis that AAA and PCC should be expressed per mL plasma in
      population studies. AAA and PCC were analyzed among 402 subjects from three
      regions of China with a gradient in hepatocellular carcinoma (HCC) mortality
      ranging from 21 to 97 per 100,000. When biomarker values were expressed per mL
      plasma, the AAA level was significantly associated with plasma PCC (r = 0.262, P
      < 0.001), and adjusted levels of AAA and PCC paralleled HCC mortalities in the
      three regions, suggesting a role for aflatoxin-related oxidative stress in
      hepatocarcinogenesis in this population. In addition, there were statistically
      significant associations between both protein biomarkers, expressed per mL
      plasma, and the levels of alanine aminotransferase and aspartate aminotransferase
      in hepatitis B virus-infected subjects, suggesting roles for aflatoxin exposure,
      oxidative stress and hepatitis B virus infection in the development of HCC. The
      present data suggest that interindividual variation in plasma protein
      concentration may influence the dosimetry and relevant interpretation of protein
      biomarkers.

PMID- 17233832
TI  - Efficient immortalization of primary human cells by p16INK4a-specific short
      hairpin RNA or Bmi-1, combined with introduction of hTERT.
AB  - Activation of telomerase is sufficient for immortalization of some types of human
      cells but additional factors may also be essential. It has been proposed that
      stress imposed by inadequate culture conditions induces senescence due to
      accumulation of p16(INK4a). Here, we present evidence that many human cell types
      undergo senescence by activation of the p16(INK4a)/Rb pathway, and that
      introduction of Bmi-1 can inhibit p16(INK4a) expression and extend the life span
      of human epithelial cells derived from skin, mammary gland and lung. Introduction
      of p16(INK4a)-specific short hairpin RNA, as well as Bmi-1, suppressed p16(INK4a)
      expression in human mammary epithelial cells without promoter methylation, and
      extended their life span. Subsequent introduction of hTERT, the telomerase
      catalytic subunit, into cells with low p16(INK4a) levels resulted in efficient
      immortalization of three cell types without crisis or growth arrest. The majority
      of the human mammary epithelial cells thus immortalized showed almost normal
      ploidy as judged by G-banding and spectral karyotyping analysis. Our data suggest
      that inhibition of p16(INK4a) and introduction of hTERT can immortalize many
      human cell types with little chromosomal instability.

PMID- 17233833
TI  - iNOS-dependent DNA damage in patients with malignant fibrous histiocytoma in
      relation to prognosis.
AB  - Malignant fibrous histiocytoma (MFH) is one of the most common soft tissue
      sarcomas. MFH has been proposed to be a lesion accompanied with inflammatory
      responses. During chronic inflammation, reactive nitrogen and oxygen species
      generated from inflammatory cells are considered to participate in carcinogenesis
      by causing DNA damage. 8-nitroguanine is a mutagenic nitrative DNA lesion formed
      during chronic inflammation. We examined whether nitrative DNA damage is related
      to the prognosis of MFH patients. We performed immunohistochemical analyses to
      examine the distribution of DNA damage and the expression of inflammation-related
      molecules including inducible nitric oxide synthase (iNOS), nuclear factor-kappaB
      (NF-kappaB), and cyclooxygenase-2 (COX-2) in clinical specimens from 25 patients
      with MFH. We also analyzed the correlation of DNA damage or the expression of
      these genes with the prognosis of MFH patients. Immunohistochemical staining
      revealed that the formation of 8-nitroguanine and 8-oxo-7,8-dihydro-2'
      deoxyguanosine (8-oxodG), an oxidative DNA lesion, occurred to a much greater
      extent in MFH tissue specimens from deceased patients than in live patients.
      iNOS, NF-kappaB and COX-2 were colocalized with 8-nitroguanine in MFH tissues. It
      is noteworthy that the statistical analysis using the Kaplan-Meier method
      demonstrated strong 8-nitroguanine staining to be associated with a poor
      prognosis. In conclusion, 8-nitroguanine appears to participate in not only the
      initiation and promotion of MFH, but also in the progression of MFH, and could
      therefore be used as a promising biomarker to evaluate the prognosis of cancer
      patients.

PMID- 17233834
TI  - Downregulation of RECK by promoter methylation correlates with lymph node
      metastasis in non-small cell lung cancer.
AB  - In the present study, we addressed the molecular mechanism of the downregulation
      of reversion-inducing-cysteine-rich protein with Kazal motifs (RECK), a critical
      tumor suppressor that can potently inhibit angiogenesis and metastasis, in non
      small cell lung cancer and its clinical significance. The methylation status of
      the RECK gene promoter was studied by methylation-specific polymerase chain
      reaction. RECK mRNA and protein levels were investigated by reverse transcription
      polymerase chain reaction and western blot analysis. Downregulation of RECK was
      observed in 60% of the 55 tumors analyzed. Using methylation-specific polymerase
      chain reaction analysis methylation of the RECK promoter was detected in 63.6%
      (35/55) of the tumor tissues. A strong correlation between downregulation and
      promoter methylation was found in these tumors (P = 0.000005). More importantly,
      downregulation of RECK significantly correlated with lymph node metastasis (P =
      0.038). Mutation of codon 12 of the K-ras gene was detected in 25.5% (14/55) of
      lung tumor tissues. Statistical analysis indicated that K-ras mutation was linked
      with RECK promoter methylation (P = 0.047) and downregulation (P = 0.023).
      Promoter methylation was also detected in human lung cancer cell lines, and the
      DNA methyltransferase inhibitor 5'-azacytidine reversed the expression of RECK
      and reduced the invasive ability of these cell lines. Collectively, our results
      suggest that downregulation of the metastasis suppressor RECK is caused by
      promoter methylation in non-small cell lung cancer and is associated with K-ras
      mutation and lymph node metastasis.

PMID- 17233835
TI  - Elevated expression of protein regulator of cytokinesis 1, involved in the growth
      of breast cancer cells.
AB  - To elucidate molecular mechanisms of mammary carcinogenesis and discover novel
      therapeutic targets for breast cancer, we previously carried out a genome-wide
      expression profile analysis of 81 breast cancer cases by means of a combination
      of cDNA microarray and laser microbeam microdissection. Among the upregulated
      genes, we focused on the functional significance of protein regulator of
      cytokinesis 1 (PRC1) in the development of breast cancer. Western blot analysis
      using breast cancer cell lines revealed a significant increase in endogenous PRC1
      levels in G(2)/M phase. Treatment of breast cancer cells with small interfering
      RNA against PRC1 effectively suppressed its expression and inhibited the growth
      of breast cancer cell lines T47D and HBC5. Furthermore, we found an interaction
      between PRC1 and kinesin family member 2C/mitotic centromere-associated kinesin
      (KIF2C/MCAK) by coimmunoprecipitation and immunoblotting using COS-7 cells, in
      which these molecules were introduced exogenously. These findings suggest the
      involvement of a PRC1-KIF2C/MCAK complex in breast tumorigenesis, and this
      complex should be a promising target for the development of novel treatments for
      breast cancer.

PMID- 17233836
TI  - Dissecting functional roles of p53 N-terminal transactivation domains by
      microarray expression analysis.
AB  - The p53 protein exerts its tumor suppressive function mainly by acting as a
      transcription activator. Two transactivation domains (TADs) located at the amino
      terminus of p53 are required for transcription activation, and the activity of
      TADs is tightly regulated by post-translational modifications, such as
      phosphorylation. We attempted to dissect the functions of the two TADs and
      phosphorylation within the TADs by analyzing p53 target genes induced by full
      length p53 (FL-p53), N-terminally deleted p53 isoform lacking the first TAD
      (Delta1stTAD) and p53 carrying point mutations at all serine residues within the
      two TADs (TAD-S/A). By performing a comprehensive survey by employing microarray
      expression analysis, the induction of target genes by FL-p53, Delta1stTAD and TAD
      S/A was analyzed. All p53s showed different target gene induction patterns,
      suggesting the importance of the two TADs and phosphorylation within the TADs in
      target gene induction. Although Delta1stTAD showed a marked decrease in the
      ability to induce genes induced by FL-p53, Delta1stTAD induced many apoptosis
      related genes that were not induced by FL-p53, suggesting the roles of these
      Delta1stTAD-induced genes in Delta1stTAD-dependent apoptosis. Approximately 80%
      of genes induced by FL-p53 were not induced by TAD-S/A, including 29 previously
      reported p53 target genes such as Hdm2 and Bax, emphasizing the importance of
      phosphorylation within the TADs. These results demonstrate the significance of
      the regulation and differential roles of the N-terminal TADs in p53
      transcriptional activity.

PMID- 17233837
TI  - Biomarker discovery: a proteomic approach for brain cancer profiling.
AB  - Gliomas in the form of astrocytomas, anaplastic astrocytomas and glioblastomas
      are the most common brain tumors in humans. Early detection of these cancers is
      crucial for successful treatment. Proteomics promises the discovery of biomarkers
      and tumor markers for early detection and diagnosis. In the current study, a
      differential gel electrophoresis technology coupled with matrix-assisted laser
      desorption/ionization-time of flight and liquid chromatography-tandem mass
      spectroscopy was used to investigate tumor-specific changes in the proteome of
      human brain cancer. Fifty human brain tissues comprising varying diagnostic
      groups (non-tumor, grade I, grade II, grade III and grade IV) were run in
      duplicate together with an internal pool sample on each gel. The proteins of
      interest were automatically picked, in-gel digested and mass spectrometry
      fingerprinted. Two hundred and eleven protein spots were identified successfully
      and were collapsed into 91 unique proteins. Approximately 20 of those 91 unique
      proteins had, to our knowledge, not been reported previously as differentially
      expressed in human brain cancer. Alb protein, peroxiredoxin 4 and SH3 domain
      binding glutamic acid-rich-like protein 3 were upregulated in glioblastoma
      multiform versus non-tumor tissues. However, aldolase C fructose-biphosphate,
      creatine kinase, B chain dihydrolipoyl dehydrogenase, enolase 2, fumarate
      hydratase, HSP60, lactoylglutathione lyase, lucine aminopeptidase, Mu-crystallin
      homolog, NADH-UO 24, neurofilament triplet L protein, septin 2, stathmin and
      vacuolar ATP synthase subunit E were downregulated in glioblastoma multiform
      compared with non-tumor tissues. These differentially expressed proteins provided
      novel information on the differences existing between normal brain and gliomas,
      and thus might prove to be useful molecular indicators of diagnostic or
      prognostic value.

PMID- 17233838
TI  - Inverse association between coffee drinking and the risk of hepatocellular
      carcinoma: a case-control study in Japan.
AB  - Coffee use has consistently been associated with lower serum liver enzyme levels
      and a reduced risk of liver cirrhosis. A limited number of cohort and case
      control studies also suggest a decreased risk of hepatocellular carcinoma (HCC)
      among coffee drinkers, but mostly without consideration of hepatitis virus
      infection. In the present case-control study, we recruited 209 incident HCC cases
      and three different controls (1308 community controls, 275 hospital controls, and
      381 patients with chronic liver disease [CLD] without HCC), all of whom were aged
      40-79 years and residents of Saga Prefecture, Japan. A questionnaire survey
      elicited information on coffee use during the last 1-2 years and 10 years before,
      and plasma hepatitis B surface antigen and antibodies to hepatitis C virus were
      tested for all but community controls. After adjustment for sex, age, heavy
      alcohol use, smoking status and hepatitis virus markers (except for community
      controls), coffee use during the last 1-2 years was associated with a decreased
      risk against any control group. For coffee use 10 years before, comparison
      between HCC cases and either community controls or CLD patients revealed a
      decreased risk; adjusted odds ratios for occasional use, 1-2 cups/day and > or =3
      cups/day compared with no use were 0.33, 0.27 and 0.22 (P trend < 0.001),
      respectively, against community controls, and 0.86, 0.62 and 0.53 (P trend =
      0.05), respectively, against CLD patients. These results suggest that coffee may
      protect against the development of HCC, yet further elaborate studies (hopefully,
      intervention studies) are warranted to corroborate these findings.

PMID- 17233839
TI  - Dipalmitoylation of radicicol results in improved efficacy against tumor growth
      and angiogenesis in vivo.
AB  - Tumor-related angiogenesis is likely to be a potential target for the treatment
      of cancer. One key to develop this angiostatic strategy would be to find useful
      angiogenesis inhibitors. Here we report the effects of radicicol, a microbial
      angiogenesis inhibitor that we previously identified using the chorioallantoic
      membrane assay, and its novel analog, 14,16-dipalmitoyl-radicicol, on tumor
      angiogenesis and growth. As expected for agents containing a penolic hydroxyl
      group, systemic administration of radicicol had little or no effect on
      neovascularization triggered by a M5076 mouse tumor cell line or a RMT-1 rat
      mammary carcinoma cell line established from autochthonous rat mammary tumors
      induced by 7,12-dimethylbenz[a]anthracene in a mouse dorsal air sac assay system.
      The agent did not show growth-inhibitory activity against either transplantable
      M5076 tumors or autochthonous 7,12-dimethylbenz[a]anthracene-induced rat mammary
      tumors. In contrast, 14,16-dipalmitoyl-radicicol potently suppressed tumor
      angiogenesis and growth in these experimental models. Furthermore, the analog
      significantly prolonged the survival rate of M5076-implanted mice. Although not
      stronger than radicicol, it dose-dependently inhibited embryonic angiogenesis in
      the chorioallantoic membrane assay, the dose required for half-maximal inhibition
      (ID(50)) value being 23 microg (27 nmol) per egg, and showed concentration
      dependent antiproliferative activity against microvascular endothelial cells in
      vitro. These data suggest that 14,16-dipalmitoyl-radicicol is a promising
      antitumor agent with antiangiogenic activity.

PMID- 17233840
TI  - Influence of histological type, smoking history and chemotherapy on survival
      after first-line therapy in patients with advanced non-small cell lung cancer.
AB  - The usual primary endpoint in clinical trials for first-line chemotherapy in
      advanced non-small cell lung cancer is overall survival. Second-line chemotherapy
      can also prolong overall survival. Non-smoking history has been associated with a
      treatment effect for epidermal growth factor receptor-tyrosine kinase inhibitor
      (EGFR-TKI) versus placebo for overall survival. We performed a retrospective
      analysis to identify prognostic factors for progression-free survival and overall
      survival in patients with advanced non-small cell lung cancer treated with first
      line carboplatin/paclitaxel, and to examine the effect of second-line therapy on
      progression-free survival and overall survival. Ninety-eight patients (median age
      61 years, 35 female, 74 adenocarcinoma, 68 smokers, 56 performance status 0)
      fulfilled our criteria, of which 75 patients (78%) received more than second-line
      therapy (docetaxel [54%] gefitinib [48%] erlotinib [4%]). For overall survival,
      smoking history and histology were significant prognostic factors. The 2-year
      overall survival rates were as follows: smokers, 17%; non-smokers, 52%, P <
      0.0001; adenocarcinoma, 40%; other 15%, P = 0.0017. Multivariate analysis in
      patients who received second-line therapy showed treatment with EGFR-TKI was an
      independent predictor of overall survival. Smoking history and adenocarcinoma
      histology were prognostic factors for an improved outcome with
      carboplatin/paclitaxel in patients with non-small cell lung cancer. Our study
      results suggest that the use of EGFR-TKI after first-line treatment may be
      associated with an improvement in overall survival.

PMID- 17233841
TI  - Reliability of the peptide nucleic acid-locked nucleic acid polymerase chain
      reaction clamp-based test for epidermal growth factor receptor mutations
      integrated into the clinical practice for non-small cell lung cancers.
AB  - Gefitinib is an inhibitor of the tyrosine kinase activity of epidermal growth
      factor receptor (EGFR). Accumulating evidence suggests that gefitinib may provide
      a survival benefit to EGFR mutation-positive non-small lung cancer patients. We
      have established a clinical test that can detect EGFR mutations from cytological
      specimens or paraffin-embedded tissue specimens that are contaminated by normal
      cells. This test is based on the peptide nucleic acid, locked nucleic acid
      polymerase chain reaction clamp method that can detect G719S, G719C, L858R, L861Q
      and seven different exon 19 deletions in the presence of 100-1000-fold wild-type
      alleles. Consequently, using a small aliquot of samples isolated to establish a
      cancer diagnosis, the EGFR mutation status is determined soon after the diagnosis
      of cancer is made. We investigated the EGFR mutation status in 86 patients using
      a variety of cytological specimens (59 bronchoscopy specimens, 16 pleural
      effusion, 9 sputum, and 2 pericardial effusion) and in 46 patients who had a
      disease relapse and paraffin-embedded tissues were available. Forty-five patients
      (34%) were positive for mutation (29 exon 19 deletions, 16 L858R and 1 L861Q).
      The sensitivity and the specificity of this test was 97% and 100%, respectively.
      EGFR mutation status thereby obtained was used to determine each patient's
      therapeutic regimen. This test is easily integrated into the normal clinical
      practice for lung cancer, while allowing the medical staff to select therapeutic
      regimen depending on the EGFR mutation status.

PMID- 17233842
TI  - The recombinant kringle domain of urokinase plasminogen activator inhibits in
      vivo malignant glioma growth.
AB  - In a previous report, the recombinant kringle domain (UK1) of the urokinase type
      plasminogen activator (uPA) showed antiangiogenic activity. Here, we investigated
      in vivo antitumor effects of the UK1 of human uPA employing a brain tumor model.
      The systemic administration of UK1 purified from pichia expression (10 and 50
      mg/kg/day intraperitoneally for 25 days) led to suppress the growth of a U87
      human glioma xenograft, implanted into the brains of male BALB/cSlc nude mice, by
      35% and 80%, respectively. In the immunohistochemical analysis, the tumors
      treated with UK1 showed decreased vascularity and expression of angiogenesis
      related factors including vascular endothelial growth factor (VEGF), angiogenin,
      alpha-smooth muscle actin, von Willebrand's factor, and CD31 (PECAM-1 [Platelet
      endothelial cell adhesion molecule-1]), and increased apoptosis. UKl inhibited
      the in vitro proliferation and tube formation of VEGF-stimulated endothelial
      cells but not the proliferation of glioma cells. These results suggest that UK1
      inhibits the malignant glioma growth by suppression of angiogenesis.

PMID- 17233843
TI  - Primary large B-cell lymphoma of the bone marrow.

PMID- 17233844
TI  - Advances in the management of alloimmune thrombocytopenia.
AB  - There have been considerable advances in the clinical and laboratory diagnosis of
      alloimmune thrombocytopenia (AIT), and its postnatal and antenatal management.
      The antenatal management of AIT has been particularly problematic, because severe
      haemorrhage occurs as early as 16 weeks gestation and there is no non-invasive
      investigation that reliably predicts the severity of AIT in utero. The strategies
      for antenatal treatment have included the use of serial platelet transfusions
      that, while effective, are invasive and associated with significant morbidity and
      mortality. Maternal therapy involving the administration of intravenous
      immunoglobulin and/or steroids is also effective and associated with fewer risks
      to the fetus. Significant recent progress has involved refinement of maternal
      treatment, stratifying it according to the likely severity of AIT based on the
      history in previous pregnancies. However, the ideal antenatal treatment, which is
      effective without causing significant side-effects to the mother or fetus, has
      yet to be determined, and further clinical trials are needed.

PMID- 17233845
TI  - Bisphosphonate incadronate inhibits growth of human T-cell leukaemia virus type I
      infected T-cell lines and primary adult T-cell leukaemia cells by interfering
      with the mevalonate pathway.
AB  - Anti-resorptive bisphosphonates are used for the treatment of hypercalcaemia and
      bone complications associated with malignancies and osteoporosis, but also have
      been shown to have anti-tumour effects in various cancers. Adult T-cell leukaemia
      (ATL) is a fatal T-cell malignancy caused by infection with human T-cell
      leukaemia virus type I (HTLV-I), and remains incurable. ATL is associated with
      osteolytic bone lesions and hypercalcaemia, both of which are major factors in
      the morbidity of ATL. Thus, the search for anti-ATL agents that have both anti
      tumour and anti-resorptive activity is warranted. The bisphosphonate agent,
      incadronate, prevented cell growth of HTLV-I-infected T-cell lines and primary
      ATL cells, but not of non-infected T-cell lines or normal peripheral blood
      mononuclear cells. Incadronate induced S-phase cell cycle arrest and apoptosis in
      HTLV-I-infected T-cell lines, and treatment of these cells with substrates of the
      mevalonate pathway blocked the incadronate-mediated growth suppression.
      Incadronate also prevented the prenylation of Rap1A protein. These results
      demonstrated that incadronate-induced growth suppression occurs by interfering
      with the mevalonate pathway. Importantly, treatment with incadronate reduced
      tumour formation from an HTLV-I-infected T-cell line when these cells were
      inoculated subcutaneously into severe combined immunodeficient mice. These
      findings suggest that incadronate could be potentially useful for the treatment
      of ATL.

PMID- 17233846
TI  - Phase II trial of denileukin diftitox for relapsed/refractory T-cell non-Hodgkin
      lymphoma.
AB  - This phase II study evaluated the safety and efficacy of denileukin diftitox, an
      interleukin-2-diphtheria toxin fusion protein, in relapsed/refractory T-cell non
      Hodgkin lymphoma (T-NHL), excluding cutaneous T-cell lymphoma. Eligible patients
      received denileukin diftitox 18 microg/kg/d x 5 d every 3 weeks for up to eight
      cycles. Tumour staging was performed every two cycles and the primary endpoint
      was the objective response rate [complete response (CR) + partial response (PR)].
      For 27 patients enrolled, median age: 55 years (range 26-80 years), 70.4% male,
      and mean prior therapies: 2.5 (range 1-6). Objective responses (six CRs, seven
      PRs) were achieved in 13 patients (48.1%), stable disease in eight (29.6%) and
      six (22.2%) had progressive disease. An objective response was achieved in eight
      of 13 patients (61.5%) with CD25(+) tumours (four CR/four PR) and five of 11
      patients (45.5%) with CD25(-) tumours (two CR/three PR). Median progression-free
      survival was 6 months (range, 1-38+ months). Most adverse reactions were grade
      1/2 and transient. No grade 4-5 toxicities were reported. Denileukin diftitox had
      significant activity and was well tolerated in relapsed/refractory T-NHL, with
      responses observed in both CD25(+) and CD25(-) tumours. Further studies of
      denileukin diftitox in combination with other agents are warranted in previously
      untreated and relapsed/refractory T-NHL.

PMID- 17233847
TI  - Remission in acute refractory and relapsing thrombotic thrombocytopenic purpura
      following rituximab is associated with a reduction in IgG antibodies to ADAMTS
      13.
AB  - Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder and
      plasma exchange (PEX) remains the primary treatment modality. Twenty-five
      patients with acute refractory/relapsing idiopathic TTP received rituximab in
      conjunction with PEX because of progressive clinical disease or deterioration in
      laboratory parameters, despite intensive standard therapy. In relapsing TTP,
      rituximab was started if antibody to ADAMTS-13 (a disintegrin and
      metalloproteinase with thrombospondin motif-13) was demonstrated during previous
      episodes. All 25 patients attained complete clinical and laboratory remission in
      a median of 11 d after initiating rituximab. In 21 cases, ADAMTS-13 activity was
      within the normal range following rituximab. Inhibitors were detected in 24/25
      patients by mixing studies and/or immunoglobulin G (IgG) antibodies to ADAMTS-13
      pre-rituximab. There was no evidence of inhibitors and/or IgG activity <10% in
      23/25 patients following rituximab. In acute refractory cases, the median number
      of PEX pre-rituximab and following the first rituximab infusion was 13 and 9,
      respectively. There have been no infectious complications, despite low CD 19
      levels and no relapses. In patients with acute refractory/relapsing idiopathic
      TTP, rituximab appears to be a safe, effective, targeted therapy with a
      significant reduction in the requirement for PEX.

PMID- 17233848
TI  - A randomised comparison of deferasirox versus deferoxamine for the treatment of
      transfusional iron overload in sickle cell disease.
AB  - Deferasirox is a once-daily, oral iron chelator developed for treating
      transfusional iron overload. Preclinical studies indicated that the kidney was a
      potential target organ of toxicity. As patients with sickle cell disease often
      have abnormal baseline renal function, the primary objective of this randomised,
      open-label, phase II trial was to evaluate the safety and tolerability of
      deferasirox in comparison with deferoxamine in this population. Assessment of
      efficacy, as measured by change in liver iron concentration (LIC) using
      biosusceptometry, was a secondary objective. A total of 195 adult and paediatric
      patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events
      most commonly associated with deferasirox were mild, including transient nausea,
      vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies
      with deferasirox were occasionally associated with mild non-progressive increases
      in serum creatinine and reversible elevations in liver function tests.
      Discontinuation rates from deferasirox (11.4%) and deferoxamine (11.1%) were
      similar. Over 1 year, similar dose-dependent LIC reductions were observed with
      deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable
      tolerability and appears to have similar efficacy to deferoxamine in reducing
      iron burden in transfused patients with sickle cell disease.

PMID- 17233849
TI  - Rapid and easy prenatal diagnosis of sickle cell anemia using double-dye LNA
      probe technology.

PMID- 17233850
TI  - G6PD Namoru (208 T--> C) is the major polymorphic variant in the tribal
      populations in southern India.

PMID- 17233851
TI  - Amendments and corrections to the 'Transfusion Guidelines for neonates and older
      children' (BCSH, 2004a); and to the 'Guidelines for the use of fresh frozen
      plasma, cryoprecipitate and cryosupernatant' (BCSH, 2004b).

PMID- 17233853
TI  - O', Evidence-based medicine--where is your effectiveness?

PMID- 17233854
TI  - Have we dismissed ablative treatment too soon in colposcopy practice?

PMID- 17233855
TI  - The use of recombinant activated factor VII in obstetric and gynaecological
      haemorrhage.
AB  - Recombinant activated factor VII (rFVIIa) was originally developed for the
      treatment of bleeding in patients with haemophilia A or B and inhibitors. Over
      the past ten years, it has been successfully used to prevent or control bleeding
      in several other nonhaemophilic bleeding conditions. Among the newer 'off-label'
      clinical applications of rFVIIa, there is increasing evidence of its
      effectiveness in treating obstetric and gynaecological bleeding unresponsive to
      conventional therapy. The existing literature on the use of rFVIIa in obstetrics
      and gynaecology is summarised in this review. Although supported by few and
      uncontrolled studies, on the whole, the published data suggest a potential role
      of rFVIIa in the management of obstetric and gynaecological intractable bleeding.
      However, further evidence is needed to improve the assessment of its optimal
      dose, effectiveness and safety in such conditions.

PMID- 17233856
TI  - Pregnancy-induced hypertension and infant mortality: Roles of birthweight
      centiles and gestational age.
AB  - OBJECTIVE: To assess the effect of pregnancy-induced hypertension (PIH) on infant
      mortality in different birthweight centiles (small for gestational age [SGA],
      appropriate for gestational age [AGA], and large for gestational age [LGA]) and
      gestational ages (early preterm, late preterm, and full term). DESIGN:
      Retrospective cohort study. SETTING: Linked birth and infant death data set of
      USA between 1995 and 2000. POPULATION: A total of 17 464 560 eligible liveborn
      singleton births delivered after 20th gestational week. METHODS: Multivariate
      logistic regression models were applied to evaluate the association between PIH
      and infant mortality, with adjustment of potential confounders stratified by
      birthweight centiles and gestational age. MAIN OUTCOME MEASURE: Infant death (0
      364 days) and its three components: early neonatal death (0-6 days), late
      neonatal death (7-27 days), and postneonatal death (28-364 days). RESULTS: PIH
      was associated with decreased risks of infant mortality, early neonatal
      mortality, and late neonatal mortality in both preterm and term SGA births, and
      PIH was associated with lower postneonatal mortality in preterm SGA births. PIH
      was associated with decreased risks of infant mortality, early neonatal
      mortality, late neonatal mortality and postneonatal mortality in preterm AGA
      births. Decreased risk of infant mortality and early neonatal mortality was
      associated with PIH in early preterm LGA births. CONCLUSIONS: The association
      between PIH and infant mortality varies depending on different birthweight
      centiles, gestational age, and age at death. PIH is associated with a decreased
      risk of infant mortality in SGA births, preterm AGA births, and early preterm LGA
      births.

PMID- 17233857
TI  - A prospective Swedish cohort study on psychosocial factors influencing anxiety in
      women referred for colposcopy.
AB  - OBJECTIVES: To elucidate risk factors for high state anxiety in women referred
      for colposcopy. DESIGN: Prospective cohort study. SETTING: Department of
      Gynaecology, Malmo University Hospital, Sweden. POPULATION: A total of 100
      consecutive women referred for colposcopy for the first time after an abnormal
      cervical smear. METHODS: Women in the study group completed prior to colposcopy
      the State-Trait Anxiety Inventory, the Montgomery-Asberg Depression Rating Scale
      self-rate, and were interviewed about their psychosocial situation. MAIN OUTCOME
      MEASURES: Variables related to high state anxiety were determined in bivariate
      and multiple logistic regression analysis. RESULTS: High depression scores and
      the wording of the referral letter for colposcopy were related to high state
      anxiety in a multivariate analysis. Women with high depression scores had a nine
      fold risk for higher levels of state anxiety and did not respond with lower state
      anxiety levels after information and examination. Women who received a letter
      stating 'some changes' were at a five-fold increased risk for high levels of
      state anxiety than those who received a letter stating 'light changes'.
      CONCLUSION: A depressive mood and the wording of the referral letter for
      colposcopy after an abnormal smear were predictive of high state anxiety levels.

PMID- 17233858
TI  - Do women with high-grade cervical intraepithelial neoplasia prefer a see and
      treat option in colposcopy?
AB  - OBJECTIVE: To compare women's experiences of either see and treat (ST) or defer
      and treat (DT) at first visit to colposcopy following abnormal cytology. DESIGN:
      A prospective postal questionnaire survey. SETTING: Colposcopy clinics of a
      University Hospital. SAMPLE: A total of 272 women with high-grade cervical
      intraepithelial neoplasia (CIN) referred to colposcopy. METHODS: A total of 136
      women receiving ST and a matched sample of women receiving DT (N = 136) were sent
      a postal questionnaire 7 days after first appointment at colposcopy to assess
      evaluations of their experience, psychological distress and relief. Subsequent
      appointment keeping was extracted from medical records. MAIN OUTCOME MEASURES:
      Anxiety and subsequent behaviour. RESULTS: Women undergoing ST were significantly
      less anxious and more relieved than those undergoing DT. They also evaluated
      their first appointment as more motivationally congruent. While women undergoing
      ST were less likely than DTs to keep their second appointment, there was no
      overall difference in did not attend (DNA) rates at 15-month follow up.
      CONCLUSIONS: ST is psychologically beneficial and may be preferred by women with
      CIN2/3.

PMID- 17233859
TI  - Women with peritoneal carcinomatosis of unknown origin: Efficacy of image-guided
      biopsy to determine site-specific diagnosis.
AB  - OBJECTIVES: To evaluate the use of image-guided biopsy (IGB) in routine clinical
      practice to obtain site-specific diagnoses in women presenting with peritoneal
      carcinomatosis (PC). STUDY DESIGN: Retrospective case study. SETTING: Tertiary
      referral centre. POPULATION: A total of 149 consecutive women with PC who
      underwent IGB. METHODS: Biopsy was performed in women considered unsuitable for
      primary surgery because of poor performance status or disease unlikely to be
      optimally debulked, with a prior history of malignancy or where there was
      clinicoradiological uncertainty about primary tumour site. Standard haematoxylin
      eosin histological analysis was supplemented with immunohistochemistry. MAIN
      OUTCOME MEASURES: The rate of site-specific diagnosis. RESULTS: A total of 149
      women underwent IGB using computed tomography or ultrasound over a 6-year period.
      The only complication was one rectus sheath haematoma. In 138 (93%) women, a site
      specific cancer diagnosis was made on the IGB (including 111 mullerian tract, 8
      gastrointestinal tract, 4 breast and 3 lymphoma); in ten women, a repeat biopsy
      was necessary, giving an overall failure rate of 7%. In a further six women,
      malignancy was confirmed but a site-specific diagnosis could not be made, and in
      four women, biopsy showed benign tissue. A site-specific diagnosis was obtained
      in 29 of the 32 women (94%) with previous malignancy, of which 18/32 (56%) showed
      a new primary cancer. CONCLUSIONS: IGB is a safe and accurate technique for
      providing site-specific diagnoses in women with PC in routine clinical practice,
      including those with a previous relevant malignancy. IGB can replace laparoscopic
      or open biopsy in defining primary therapeutic options. The data would suggest
      that the biopsy should be performed with ultrasound where feasible.

PMID- 17233860
TI  - Improving the existing diagnostic strategy by accounting for characteristics of
      the women in the diagnostic work up for postmenopausal bleeding.
AB  - OBJECTIVES: The aim of this study was to evaluate whether the efficiency of the
      current diagnostic work up following postmenopausal bleeding could be improved by
      diagnostic strategies that take into account characteristics of the women in
      addition to the currently recommended transvaginal measurement of endometrial
      thickness to determine for subsequent histological assessment. DESIGN:
      Multicenter, prospective cohort study. SETTING: A university hospital and seven
      teaching hospitals in the Netherlands. SAMPLE: Consecutive women not using
      hormone replacement therapy, presenting with postmenopausal bleeding. METHODS:
      Five hundred and forty women underwent transvaginal sonography, and in case of
      endometrial thickness (double layer) above 4 mm, subsequent endometrial sampling
      was performed. Presence of carcinoma was ruled out by the absence of
      abnormalities in histological specimen or by an uneventful follow up of at least
      6 months. MAIN OUTCOME MEASURES: Probability of endometrial carcinoma was
      estimated by multivariable logistic regression models. For each diagnostic
      strategy, we calculated diagnostic accuracy (area under receiver operating
      characteristic curve [AUC]), negative predictive value (NPV) and the number of
      diagnostic procedures. RESULTS: A strategy with transvaginal sonography alone
      with a fixed threshold incorrectly classified 0.7% of the women as nonmalignant
      (NPV: 99.3% [98.5-100%]), with 97% sensitivity and 56% specificity. A strategy
      integrating characteristics of the women with transvaginal sonography could
      result in less false reassurances (NPV: 99.6% [99.2-100%]), with only marginal
      decrease in diagnostic procedures, or a minor increase in false reassurances
      (NPV: 99.0% [98.3-100%]), with a substantial reduction (15-20%) in the
      procedures. AUCs associated with these strategies could improve from 0.76 (0.73
      0.79) for transvaginal sonography alone to 0.90 (0.87-0.93) for the integrated
      strategy. CONCLUSION: Taking into account the characteristics of the women could
      increase the efficiency of the diagnostic work up for postmenopausal bleeding.

PMID- 17233861
TI  - Feasibility of screening for ovarian cancer using symptoms as selection criteria.
AB  - OBJECTIVE: Retrospective studies have reported that 95% of women with ovarian
      cancer have symptoms prior to diagnosis and that women with these symptoms are at
      an increased risk of ovarian cancer. Failure to recognise these symptoms may
      result in a delay in referral and diagnosis. We assess the feasibility of
      screening for ovarian cancer using symptoms as selection criteria. DESIGN: A
      randomised controlled trial. SETTING: General practices in East London.
      POPULATION: Three hundred and ninety GPs. METHODS: GPs were randomised by
      practice, and those in the study group were given rapid access to ultrasound and
      CA125 test for women, >45 years, suffering from symptoms that may be caused by
      ovarian cancer. MAIN OUTCOME MEASURES: Symptoms leading to referral, ultrasound
      and CA125 results and ovarian cancer diagnosis. RESULTS: Seventy nine practices
      containing 197 GPs were randomised to the study arm. Three hundred and seventeen
      women were referred, of which 315 were eligible. Women reported the following
      symptoms: abdominal 87%, gastrointestinal 41% and constitutional 29%. Twenty
      three women had abnormal findings on ultrasound: 20 were managed conservatively
      and 3 surgically. Histology revealed a mucinous cystadenoma, a Brenner tumour and
      a serous cystadenoma. Incidental findings included endometrial pathology in 13
      women and bladder pathology in 2. Ninety five percent of CA125 results were <35
      units/ml. CONCLUSIONS: This pilot study confirms the feasibility of screening for
      ovarian cancer using symptoms as selection criteria. Specificity was high and
      patient compliance good. Initial concerns about referral volumes and additional
      investigations and referrals generated were not confirmed. No ovarian cancers
      were detected in this pilot study, and this may be due to the size of the cohort.

PMID- 17233862
TI  - Maternal pseudo primary hyperaldosteronism in twin-to-twin transfusion syndrome.
AB  - OBJECTIVE: To monitor changes in the maternal renin-angiotensin-aldosterone
      system following laser therapy and amnioreduction in severe twin-to-twin
      transfusion syndrome (TTTS). DESIGN: Observational prospective study. SETTING:
      Single university hospital in Poissy, France. POPULATION: Sixty cases of TTTS at
      16-26 weeks of gestation. METHOD: Maternal blood sampling before, 6 and 24 hours
      following the procedure. MAIN OUTCOME MEASURES: Plasma levels of aldosterone,
      renin, angiotensin II (AII), atrial natriuretic peptide (ANP), vasopressin,
      sodium, potassium and plasma proteins together with full blood count were
      measured before, 6 and 24 hours following the procedure. RESULTS: TTTS is
      associated with maternal hyperaldosteronism dissociated from renin-angiotensin
      changes. Correcting TTTS by placental surgery and amnioreduction triggers
      incomplete correction of hyperaldosteronism, as early as 6 hours following the
      procedure, without changes in AII but an increase in the levels of ANP in plasma.
      Electrolyte concentrations remained stable despite haemodilution, while
      vasoactive hormone levels such as that of vasopressin remained unchanged.
      CONCLUSION: Mechanisms involved in marked fluid retention in TTTS are rapidly
      corrected by laser therapy followed by amnioreduction while maintaining
      electrolyte homeostasis.

PMID- 17233863
TI  - Decision making about mode of delivery among pregnant women who have previously
      had a caesarean section: A qualitative study.
AB  - OBJECTIVE: To explore prospectively women's decision making regarding mode of
      delivery after a previous caesarean section. MAIN OUTCOME MEASURES: The evolution
      of decision making, women's participation in decision making, and factors
      affecting decision making. DESIGN AND METHODS: A qualitative study using diaries,
      observations and semi-structured interviews. Data were analysed thematically from
      both a longitudinal and a cross-sectional perspective. SETTING: An antenatal unit
      in a large teaching hospital in Scotland and participants' homes. SAMPLE: Twenty
      six women who had previously had a caesarean section for a nonrecurrent cause.
      RESULTS: Women were influenced by their own previous experiences and
      expectations, and the final decision on mode of delivery often developed during
      the course of the pregnancy. Most acknowledged that any decision was provisional
      and might change if circumstances necessitated. Despite a universal desire to be
      involved in the process, many women did not participate actively and were
      uncomfortable with having responsibility for decision making. Feelings about the
      amount and quality of the information received regarding delivery options varied
      greatly, with many women wishing for information to be tailored to their
      individual clinical circumstances and needs. In contrast to the impression
      created in the media, there was no evidence of clear preferences or strong
      demands for elective caesarean section. CONCLUSION: Women who have had a previous
      caesarean section do not usually have firm ideas about mode of delivery. They
      look for targeted information and guidance from medical personnel based on their
      individual circumstances, and some are unhappy with the responsibility of
      deciding how to deliver in the current pregnancy.

PMID- 17233864
TI  - Stress symptoms and burnout in obstetric and gynaecology residents.
AB  - OBJECTIVE: This study was designed to examine the burnout syndrome among
      residents in obstetrics and gynaecology in Spain, and to analyse the predisposing
      factors for this condition. SETTING: Eight Spanish University hospitals. SAMPLE:
      A total of 162 residents representative of all active residents in obstetrics and
      gynaecology in Spain with regards to age, sex and year of residency were asked to
      take part in this survey. METHODS: The Maslach Burnout Inventory was mailed to
      each resident of eight Spanish hospitals representative of all active residents
      in obstetrics and gynaecology in Spain with regards to age, sex and year of
      residency. Burnout was defined as a high score on the emotional exhaustion or
      depersonalisation subscores, according to validated standard cutoff values. The
      demographic and predisposing work factors were noted for each participant using a
      self-reported questionnaire. A binary logistic regression model was constructed
      from all predisposing factors as covariates for the prediction of the burnout
      syndrome. RESULTS: Sixty-seven percent of the 162 eligible residents returned
      their questionnaires within a 3-month period. Of those, 58% fulfilled the
      criteria for the burnout syndrome. In the multivariate analysis, marital status
      and workload in office practice were found to be significant predisposing
      factors. Single marital status increased the odds ratio for burnout by 5.2 (95%
      CI 1.3-21). For every extra ten patients attended in the office per week, the
      odds ratio for burnout increased by 1.25 (95% CI 1.0-1.5). A stratified
      multivariate subanalysis showed that this risk remained significant only in the
      group of residents without staff supervision with an odds ratio of 2.1 (95% CI
      1.3-2.9). CONCLUSION: The prevalence of the burnout syndrome during obstetrics
      and gynaecology residency is high. Single marital status and workload in office
      practice without staff supervision are significant predisposing factors.

PMID- 17233865
TI  - The relationship between pre-pregnancy care and early pregnancy loss, major
      congenital anomaly or perinatal death in type I diabetes mellitus.
AB  - The relationships between markers of pregnancy planning and pre-pregnancy care
      and adverse outcomes (early pregnancy loss, major congenital anomaly and
      perinatal death) were examined in 423 singleton pregnancies in women with pre
      gestational type I diabetes mellitus. Pregnancy planning and markers of pre
      pregnancy care were associated with reduced risks of adverse pregnancy outcomes.
      'Documentation of achievement of an optimal haemoglobin A1c prior to
      discontinuation of contraception' was the marker associated with the lowest rate
      of adverse outcome (OR 0.2; 95% CI 0.06-0.67) and might serve as an appropriate
      definition of pre-pregnancy care for research and audit purposes.

PMID- 17233866
TI  - The use of a perinatal internet consultation forum in Israel.
AB  - To analyse the use of a free, public, perinatal internet consultation service,
      2000 consultations provided by university hospital staff were evaluated over 30
      months. Ninety five percent of the questioners were women, and 62% of them were
      primiparous. The average response rate was 2.3 audience responses per question.
      Fifty-two percent of the consultations were related to labour and delivery, 23%
      were related to pregnancy complications, 16% were related to prenatal diagnosis,
      and 7% were related to the puerperium period. We conclude that medical
      consultation forums provide an additional way of delivering inexpensive,
      accessible, fast, and convenient healthcare services.

PMID- 17233867
TI  - Necrotising fasciitis following unrecognised bladder injury during transobturator
      sling procedure.

PMID- 17233868
TI  - Vaginal delivery after surgical treatment for stress incontinence using
      transobturator tape: A case report.

PMID- 17233869
TI  - Regarding radical vaginal trachelectomy as a fertility-sparing procedure in women
      with early-stage cervical cancer-cumulative pregnancy rate in a series of 123
      women.

PMID- 17233870
TI  - Obesity, waist-hip ratio and hunter-gatherers.

PMID- 17233871
TI  - Economic evaluation of alternative management methods of first-trimester
      miscarriage based on results from the miscarriage treatment (MIST) trial by
      Petrou et al.

PMID- 17233873
TI  - Improving the accuracy of estimated blood loss at obstetric haemorrhage using
      clinical reconstructions.

PMID- 17233874
TI  - Random albumin/creatinine ratio for quantification of proteinuria in manifest pre
      eclampsia.

PMID- 17233875
TI  - Random albumin/creatinine ratio for quantification of proteinuria in manifest pre
      eclampsia.

PMID- 17233878
TI  - Don't we want aroused and alert babies at birth?

PMID- 17233881
TI  - The epidemiology of malaria in adults in a rural area of southern Mozambique.
AB  - BACKGROUND: Epidemiological studies of malaria in adults who live in malaria
      endemic areas are scarce. More attention to the natural history of malaria
      affecting adults is needed to understand the dynamics of malaria infection and
      its interaction with the immune system. The present study was undertaken to
      investigate the clinical, parasitological and haematological status of adults
      exposed to malaria, and to characterize parasites in these individuals who
      progressively acquire protective immunity. METHODS: A cross-sectional survey of
      249 adults was conducted in a malaria endemic area of Mozambique. Clinical,
      parasitological and haematological status of the study population was recorded.
      Sub-microscopic infections and multiplicity of infections were investigated using
      polymerase chain reaction (PCR) and restriction fragment length polymorphism of
      Plasmodium falciparum merozoite surface protein 2 (msp2). RESULTS: Prevalence of
      P. falciparum infection by microscopy (14%) and PCR (42%) decreased progressively
      during adulthood, in parallel with an increase in the prevalence of sub
      microscopic infections. Anaemia was only related to parasitaemia as detected by
      PCR. Multiplicity of infection decreased with age and was higher in subjects with
      high P. falciparum densities, highlighting density-dependent constraints upon the
      PCR technique. CONCLUSION: Adults of Manhica progressively develop non-sterile,
      protective immunity against P. falciparum malaria. The method of parasite
      detection has a significant effect on the observed natural history of malaria
      infections. A more sensitive definition of malaria in adults should be
      formulated, considering symptoms such as diarrhoea, shivering and headache,
      combined with the presence of parasitaemia.

PMID- 17233882
TI  - Metabolic mapping by use of high-resolution magic angle spinning 1H MR
      spectroscopy for assessment of apoptosis in cervical carcinomas.
AB  - BACKGROUND: High-resolution magic angle proton magnetic resonance spectroscopy
      (HR 1H MAS MRS) provides a broad metabolic mapping of intact tumor samples and
      allows for microscopy investigations of the samples after spectra acquisition.
      Experimental studies have suggested that the method can be used for detection of
      apoptosis, but this has not been investigated in a clinical setting so far. We
      have explored this hypothesis in cervical cancers by searching for metabolites
      associated with apoptosis that were not influenced by other histopathological
      parameters like tumor load and tumor cell density. METHODS: Biopsies (n = 44)
      taken before and during radiotherapy in 23 patients were subjected to HR MAS MRS.
      A standard pulse-acquire spectrum provided information about lipids, and a spin
      echo spectrum enabled detection of non-lipid metabolites in the lipid region of
      the spectra. Apoptotic cell density, tumor cell fraction, and tumor cell density
      were determined by histopathological analysis after spectra acquisition. RESULTS:
      The apoptotic cell density correlated with the standard pulse-acquire spectra (p
      < 0.001), but not with the spin-echo spectra, showing that the lipid metabolites
      were most important. The combined information of all lipids contributed to the
      correlation, with a major contribution from the ratio of fatty acid -CH2 to CH3
      (p = 0.02). In contrast, the spin-echo spectra contained the main information on
      tumor cell fraction and tumor cell density (p < 0.001), for which cholines,
      creatine, taurine, glucose, and lactate were most important. Significant
      correlations were found between tumor cell fraction and glucose concentration (p
      = 0.001) and between tumor cell density and glycerophosphocholine (GPC)
      concentration (p = 0.024) and ratio of GPC to choline (p < 0.001). CONCLUSION:
      Our findings indicate that the apoptotic activity of cervical cancers can be
      assessed from the lipid metabolites in HR MAS MR spectra and that the HR MAS data
      may reveal novel information on the metabolic changes characteristic of
      apoptosis. These changes differed from those associated with tumor load and tumor
      cell density, suggesting an application of the method to explore the role of
      apoptosis in the course of the disease.

PMID- 17233883
TI  - Malaria vectors and transmission dynamics in coastal south-western Cameroon.
AB  - BACKGROUND: Malaria is a major public health problem in Cameroon. Unlike in the
      southern forested areas where the epidemiology of malaria has been better studied
      prior to the implementation of control activities, little is known about the
      distribution and role of anophelines in malaria transmission in the coastal
      areas. METHODS: A 12-month longitudinal entomological survey was conducted in
      Tiko, Limbe and Idenau from August 2001 to July 2002. Mosquitoes captured indoors
      on human volunteers were identified morphologically. Species of the Anopheles
      gambiae complex were identified using the polymerase chain reaction (PCR).
      Mosquito infectivity was detected by the enzyme-linked immunosorbent assay and
      PCR. Malariometric indices (plasmodic index, gametocytic index, parasite species
      prevalence) were determined in three age groups (<5 yrs, 5-15 yrs, >15 yrs) and
      followed-up once every three months. RESULTS: In all, 2,773 malaria vectors
      comprising Anopheles gambiae (78.2%), Anopheles funestus (17.4%) and Anopheles
      nili (7.4%) were captured. Anopheles melas was not anthropophagic. Anopheles
      gambiae had the highest infection rates. There were 287, 160 and 149 infective
      bites/person/year in Tiko, Limbe and Idenau, respectively. Anopheles gambiae
      accounted for 72.7%, An. funestus for 23% and An. nili for 4.3% of the
      transmission. The prevalence of malaria parasitaemia was 41.5% in children <5
      years of age, 31.5% in those 5-15 years and 10.5% in those >15 years, and
      Plasmodium falciparum was the predominant parasite species. CONCLUSION: Malaria
      transmission is perennial, rainfall dependent and An. melas does not contribute
      to transmission. These findings are important in the planning and implementation
      of malaria control activities in coastal Cameroon and West Africa.

PMID- 17233884
TI  - Stromelysin-3 over-expression enhances tumourigenesis in MCF-7 and MDA-MB-231
      breast cancer cell lines: involvement of the IGF-1 signalling pathway.
AB  - BACKGROUND: Stromelysin-3 (ST-3) is over-expressed in the majority of human
      carcinomas including breast carcinoma. Due to its known effect in promoting
      tumour formation, but its impeding effect on metastasis, a dual role of ST-3 in
      tumour progression, depending on the cellular grade of dedifferentiation, was
      hypothesized. METHODS: The present study was designed to investigate the
      influence of ST-3 in vivo and in vitro on the oestrogen-dependent, non-invasive
      MCF-7 breast carcinoma cell line as well as on the oestrogen-independent,
      invasive MDA-MB-231 breast carcinoma cell line. Therefore an orthotopic human
      xenograft tumour model in nude mice, as well as a 3D matrigel cell culture
      system, were employed. RESULTS: Using both in vitro and in vivo techniques, we
      have demonstrated that over-expression of ST-3 in MCF-7 and MDA-MB-231 cells
      leads to both increased cell numbers and tumour volumes. This observation was
      dependent upon the presence of growth factors. In particular, the enhanced
      proliferative capacity was in MCF-7/ST-3 completely and in MDA-MB-231/ST-3 cells
      partially dependent on the IGF-1 signalling pathway. Microarray analysis of ST-3
      over-expressing cells revealed that in addition to cell proliferation, further
      biological processes seemed to be affected, such as cell motility and stress
      response. The MAPK-pathway as well as the Wnt and PI3-kinase pathways, appear to
      also play a potential role. Furthermore, we have demonstrated that breast cancer
      cell lines of different differentiation status, as well as the non-tumourigenic
      cell line MCF-10A, have a comparable capability to induce endogenous ST-3
      expression in fibroblasts. CONCLUSION: These data reveal that ST-3 is capable of
      enhancing tumourigenesis in highly differentiated "early stage" breast cancer
      cell lines as well as in further progressed breast cancer cell lines that have
      already undergone epithelial-mesenchymal transition. We propose that ST-3
      induction in tumour fibroblasts leads to the stimulation of the IGF-1R pathway in
      carcinoma cells, thus enhancing their proliferative capacity. In addition,
      further different cellular processes seem to be activated by ST-3, possibly
      accounting for the dual role of ST-3 in tumour progression and metastasis.

PMID- 17233885
TI  - Antisense oligonucleotide-induced alternative splicing of the APOB mRNA generates
      a novel isoform of APOB.
AB  - BACKGROUND: Apolipoprotein B (APOB) is an integral part of the LDL, VLDL, IDL,
      Lp(a) and chylomicron lipoprotein particles. The APOB pre-mRNA consists of 29
      constitutively-spliced exons. APOB exists as two natural isoforms: the full
      length APOB100 isoform, assembled into LDL, VLDL, IDL and Lp(a) and secreted by
      the liver in humans; and the C-terminally truncated APOB48, assembled into
      chylomicrons and secreted by the intestine in humans. Down-regulation of APOB100
      is a potential therapy to lower circulating LDL and cholesterol levels. RESULTS:
      We investigated the ability of 2'O-methyl RNA antisense oligonucleotides (ASOs)
      to induce the skipping of exon 27 in endogenous APOB mRNA in HepG2 cells. These
      ASOs are directed towards the 5' and 3' splice-sites of exon 27, the branch-point
      sequence (BPS) of intron 26-27 and several predicted exonic splicing enhancers
      within exon 27. ASOs targeting either the 5' or 3' splice-site, in combination
      with the BPS, are the most effective. The splicing of other alternatively spliced
      genes are not influenced by these ASOs, suggesting that the effects seen are not
      due to non-specific changes in alternative splicing. The skip 27 mRNA is
      translated into a truncated isoform, APOB87SKIP27. CONCLUSION: The induction of
      APOB87SKIP27 expression in vivo should lead to decreased LDL and cholesterol
      levels, by analogy to patients with hypobetalipoproteinemia. As intestinal APOB
      mRNA editing and APOB48 expression rely on sequences within exon 26, exon 27
      skipping should not affect APOB48 expression unlike other methods of down
      regulating APOB100 expression which also down-regulate APOB48.

PMID- 17233886
TI  - Rat models of acute inflammation: a randomized controlled study on the effects of
      homeopathic remedies.
AB  - BACKGROUND: One of the cardinal principles of homeopathy is the "law of
      similarities", according to which patients can be treated by administering
      substances which, when tested in healthy subjects, cause symptoms that are
      similar to those presented by the patients themselves. Over the last few years,
      there has been an increase in the number of pre-clinical (in vitro and animal)
      studies aimed at evaluating the pharmacological activity or efficacy of some
      homeopathic remedies under potentially reproducible conditions. However, in
      addition to some contradictory results, these studies have also highlighted a
      series of methodological difficulties.The present study was designed to explore
      the possibility to test in a controlled way the effects of homeopathic remedies
      on two known experimental models of acute inflammation in the rat. To this aim,
      the study considered six different remedies indicated by homeopathic practice for
      this type of symptom in two experimental edema models (carrageenan- and
      autologous blood-induced edema), using two treatment administration routes (sub
      plantar injection and oral administration). METHODS: In a first phase, the
      different remedies were tested in the four experimental conditions, following a
      single-blind (measurement) procedure. In a second phase, some of the remedies (in
      the same and in different dilutions) were tested by oral administration in the
      carrageenan-induced edema, under double-blind (treatment administration and
      measurement) and fully randomized conditions. Seven-hundred-twenty male Sprague
      Dawley rats weighing 170-180 g were used. Six homeopathic remedies (Arnica
      montana D4, Apis mellifica D4, D30, Atropa belladonna D4, Hamamelis virginiana
      D4, Lachesis D6, D30, Phosphorus D6, D30), saline and indomethacin were tested.
      Edema was measured using a water-based plethysmometer, before and at different
      times after edema induction. Data were analyzed by ANOVA and Student t test.
      RESULTS: In the first phase of experiments, some statistically significant
      effects of homeopathic remedies (Apis, Lachesis and Phosporus) were observed (the
      reduction in paw volume increase ranging from 10% to 28% at different times since
      edema induction). In the second phase of experiments, the effects of homeopathic
      remedies were not confirmed. On the contrary, the unblinded standard allopathic
      drug indomethacin exhibited its anti-inflammatory effect in both experimental
      phases (the reduction in paw volume increase ranging from 14% to 40% in the first
      phase, and from 18% to 38% in the second phase of experiments). CONCLUSION: The
      discrepancies between single-blind and double-blind methods in animal
      pharmacological research are noteworthy and should be better investigated, also
      in non-homeopathic research.

PMID- 17233887
TI  - Molecular identification of Palearctic members of Anopheles maculipennis in
      northern Iran.
AB  - BACKGROUND: Members of Anopheles maculipennis complex are effective malaria
      vectors in Europe and the Caspian Sea region in northern Iran, where malaria has
      been re-introduced since 1994. The current study has been designed in order to
      provide further evidence on the status of species composition and to identify
      more accurately the members of the maculipennis complex in northern Iran.
      METHODS: The second internal transcribed spacer of ribosomal DNA (rDNA-ITS2) was
      sequenced in 28 out of 235 specimens that were collected in the five provinces of
      East Azerbayjan, Ardebil, Guilan, Mazandaran and Khorassan in Iran. RESULTS: The
      length of the ITS2 ranged from 283 to 302 bp with a GC content of 49.33-54.76%.
      No intra-specific variations were observed. Construction of phylogenetic tree
      based on the ITS2 sequence revealed that the six Iranian members of the
      maculipennis complex could be easily clustered into three groups: the An.
      atroparvus-Anopheles labranchiae group; the paraphyletic group of An.
      maculipennis, An. messeae, An. persiensis; and An. sacharovi as the third group.
      CONCLUSION: Detection of three species of the An. maculipennis complex including
      An. atroparvus, An. messae and An. labranchiae, as shown as new records in
      northern Iran, is somehow alarming. A better understanding of the epidemiology of
      malaria on both sides of the Caspian Sea may be provided by applying the
      molecular techniques to the correct identification of species complexes, to the
      detection of Plasmodium composition in Anopheles vectors and to the status of
      insecticide resistance by looking to related genes.

PMID- 17233888
TI  - The dystrotelin, dystrophin and dystrobrevin superfamily: new paralogues and old
      isoforms.
AB  - BACKGROUND: Dystrophins and dystrobrevins are distantly related proteins with
      important but poorly understood roles in the function of metazoan muscular and
      neuronal tissues. Defects in them and their associated proteins cause a range of
      neuromuscular disorders. Members of this superfamily have been discovered in a
      relatively serendipitous way; we set out to compile a comprehensive description
      of dystrophin- and dystrobrevin-related sequences from available metazoan genome
      sequences, validated in representative organisms by RT-PCR, or acquired de novo
      from key species. RESULTS: Features of the superfamily revealed by our survey
      include: a) Dystrotelin, an entirely novel branch of the superfamily, present in
      most vertebrates examined. Dystrotelin is expressed in the central nervous
      system, and is a possible orthologue of Drosophila DAH. We describe the
      preliminary characterisation of its function, evolution and expression. b) A
      novel vertebrate member of the dystrobrevin family, gamma-dystrobrevin, an
      ancient branch now extant only in fish, but probably present in our own
      ancestors. Like dystrophin, zebrafish gamma-dystrobrevin mRNA is localised to
      myosepta. c) The extent of conservation of alternative splicing and alternative
      promoter use in the dystrophin and dystrobrevin genes; alternative splicing of
      dystrophin exons 73 and 78 and alpha-dystrobrevin exon 13 are conserved across
      vertebrates, as are the use of the Dp116, Dp71 and G-utrophin promoters; the
      Dp260 and Dp140 promoters are tetrapod innovations. d) The evolution of the
      unique N-terminus of DRP2 and its relationship to Dp116 and G-utrophin. e) A C
      terminally truncated common ancestor of dystrophin and utrophin in cyclostomes.
      f) A severely restricted repertoire of dystrophin complex components in
      ascidians. CONCLUSION: We have refined our understanding of the evolutionary
      history and isoform diversity of the five previously reported vertebrate
      superfamily members and describe two novel members, dystrotelin and gamma
      dystrobrevin. Dystrotelins, dystrophins and dystrobrevins are roughly equally
      related to each other. Vertebrates therefore have a repertoire of seven
      superfamily members (three dystrophins, three dystrobevins, and one dystrotelin),
      with one lost in tetrapods. Most invertebrates studied have one member from each
      branch. Although the basic shared function which is implied by the common
      architecture of these distantly related proteins remains unclear, it clearly
      permeates metazoan biology.

PMID- 17233889
TI  - The Francisella pathogenicity island protein IglA localizes to the bacterial
      cytoplasm and is needed for intracellular growth.
AB  - BACKGROUND: Francisella tularensis is a gram negative, facultative intracellular
      bacterium that is the etiological agent of tularemia. F. novicida is closely
      related to F. tularensis but has low virulence for humans while being highly
      virulent in mice. IglA is a 21 kDa protein encoded by a gene that is part of an
      iglABCD operon located on the Francisella pathogenicity island (FPI). RESULTS:
      Bioinformatics analysis of the FPI suggests that IglA and IglB are components of
      a newly described type VI secretion system. In this study, we showed that IglA
      regulation is controlled by the global regulators MglA and MglB. During
      intracellular growth IglA production reaches a maximum at about 10 hours post
      infection. Biochemical fractionation showed that IglA is a soluble cytoplasmic
      protein and immunoprecipitation experiments demonstrate that it interacts with
      the downstream-encoded IglB. When the iglB gene was disrupted IglA could not be
      detected in cell extracts of F. novicida, although IglC could be detected. We
      further demonstrated that IglA is needed for intracellular growth of F. novicida.
      A non-polar iglA deletion mutant was defective for growth in mouse macrophage
      like cells, and in cis complementation largely restored the wild type macrophage
      growth phenotype. CONCLUSION: The results of this study demonstrate that IglA and
      IglB are interacting cytoplasmic proteins that are required for intramacrophage
      growth. The significance of the interaction may be to secrete effector molecules
      that affect host cell processes.

PMID- 17233890
TI  - Conserved alternative and antisense transcripts at the programmed cell death 2
      locus.
AB  - BACKGROUND: The programmed cell death 2 (Pdcd2) gene on mouse chromosome 17 was
      evaluated as a member of a highly conserved synteny, a candidate for an imprinted
      locus, and a candidate for the Hybrid sterility 1 (Hst1) gene. RESULTS: New mouse
      transcripts were identified at this locus: an alternative Pdcd2 mRNA skipping the
      last two coding exons and two classes of antisense RNAs. One class of the
      antisense RNA overlaps the alternative exon and the other the entire Pdcd2 gene.
      The antisense RNAs are alternative transcripts of the neighboring TATA-binding
      protein gene (Tbp) that are located mainly in the cell nucleus. Analogous
      alternative PDCD2 forms truncating the C-terminal domain were also detected in
      human and chicken. Alternative transcripts of the chicken PDCD2 and TBP genes
      also overlap. No correlation in the transcription of the alternative and
      overlapping mRNAs was detected. Allelic sequencing and transcription studies did
      not reveal any support for the candidacy of Pdcd2 for Hst1. No correlated
      expression of Pdcd2 with the other two genes of the highly conserved synteny was
      observed. Pdcd2, Chd1, and four other genes from this region were not imprinted
      in the embryo. CONCLUSION: The conservation of alternative transcription of the
      Pdcd2 gene in mouse, human and chicken suggests the biological importance of such
      truncated protein. The biological function of the alternative PDCD2 is likely to
      be opposite to that of the constitutive form. The ratio of the constitutive and
      alternative Pdcd2 mRNAs differs in the tissues, suggesting a developmental role.
      The identified Tbp-alternative Pdcd2-antisense transcripts may interfere with the
      transcription of the Pdcd2 gene, as they are transcribed at a comparable level.
      The conservation of the Pdcd2/Tbp sense-antisense overlap in the mouse and
      chicken points out its biological relevance. Our results also suggest that some
      cDNAs in databases labeled as noncoding are incomplete alternative cDNAs of
      neighboring protein-coding genes.

PMID- 17233891
TI  - Striking variations in consultation rates with general practice reveal family
      influence.
AB  - BACKGROUND: The reasons why patients decide to consult a general practitioner
      vary enormously. While there may be individual reasons for this variation, the
      family context has a significant and unique influence upon the frequency of
      individuals' visits. The objective of this study was to explore which family
      factors can explain the differences between strikingly high, and correspondingly
      low, family consultation rates in families with children aged up to 21. METHODS:
      Data were used from the second Dutch national survey of general practice. This
      survey extracted from the medical records of 96 practices in the Netherlands,
      information on all consultations with patients during 2001. We defined, through
      multilevel analysis, two groups of families. These had respectively,
      predominantly high, and low, contact frequencies due to a significant family
      influence upon the frequency of the individual's first contacts. Binomial
      logistic regression analyses were used to analyse which of the family factors,
      related to shared circumstances and socialisation conditions, can explain the
      differences in consultation rates between the two groups of families. RESULTS: In
      almost 3% of all families, individual consultation rates decrease significantly
      due to family influence. In 11% of the families, individual consultation rates
      significantly increase due to family influence. While taking into account the
      health status of family members, family factors can explain family consultation
      rates. These factors include circumstances such as their economic status and
      number of children, as well as socialisation conditions such as specific health
      knowledge and family beliefs. The chance of significant low frequencies of
      contact due to family influences increases significantly with factors such as,
      paid employment of parents in the health care sector, low expectations of general
      practitioners' care for minor ailments and a western cultural background.
      CONCLUSION: Family circumstances can easily be identified and will add to the
      understanding of the health complaints of the individual patient in the
      consulting room. Family circumstances related to health risks often cannot be
      changed but they can illuminate the reasons for a visit, and mould strategies for
      prevention, treatment or recovery. Health beliefs, on the other hand, may be
      influenced by providing specific knowledge.

PMID- 17233892
TI  - EDGEdb: a transcription factor-DNA interaction database for the analysis of C.
      elegans differential gene expression.
AB  - BACKGROUND: Transcription regulatory networks are composed of protein-DNA
      interactions between transcription factors and their target genes. A long-term
      goal in genome biology is to map protein-DNA interaction networks of all
      regulatory regions in a genome of interest. Both transcription factor -and gene
      centered methods can be used to systematically identify such interactions. We use
      high-throughput yeast one-hybrid assays as a gene-centered method to identify
      protein-DNA interactions between regulatory sequences (e.g. gene promoters) and
      transcription factors in the nematode Caenorhabditis elegans. We have already
      mapped several hundred protein-DNA interactions and analyzed the transcriptional
      consequences of some by examining differential gene expression of targets in the
      presence or absence of an upstream regulator. The rapidly increasing amount of
      protein-DNA interaction data at a genome scale requires a database that
      facilitates efficient data storage, retrieval and integration. DESCRIPTION: Here,
      we report the implementation of a C. elegans differential gene expression
      database (EDGEdb). This database enables the storage and retrieval of protein-DNA
      interactions and other data that relate to differential gene expression.
      Specifically, EDGEdb contains: i) sequence information of regulatory elements,
      including gene promoters, ii) sequence information of all 934 predicted
      transcription factors, their DNA binding domains, and, where available, their
      dimerization partners and consensus DNA binding sites, iii) protein-DNA
      interactions between regulatory elements and transcription factors, and iv)
      expression patterns conferred by regulatory elements, and how such patterns are
      affected by interacting transcription factors. CONCLUSION: EDGEdb provides a
      protein-DNA -and protein-protein interaction resource for C. elegans
      transcription factors and a framework for similar databases for other organisms.
      The database is available at http://edgedb.umassmed.edu.

PMID- 17233893
TI  - Reconciling competing priorities in commissioning: the future of bone
      densitometry service for North Wales.
AB  - BACKGROUND: Osteoporosis creates brittle bones susceptible to fracture, with
      resulting high levels of morbidity and mortality. Poor access to bone
      densitometry services for the residents of North Wales led to the Welsh Assembly
      Government offering capital to purchase a dual-energy X-ray absorptiometry (DXA)
      scanner, used to diagnose osteoporosis, for the region. The commissioning
      question for the six Local Health Boards across North Wales was where to site the
      new scanner. This decision needed to reflect current inequalities in access to
      services and concerns over inappropriate prescribing relative to Welsh norms.
      METHODS: Epidemiological, corporate and comparative healthcare needs assessments
      were performed. In addition, two cross-sectional surveys were conducted to
      determine the views of general practices and users of bone densitometry services
      resident in North Wales. An option appraisal and sensitivity analysis of 13
      costed options for DXA scanning was conducted. RESULTS: We estimated that only
      31% of the people in North Wales who met national guidelines were receiving DXA
      scans. There was definite inequity of access to the current service provided by
      area of residence. There was also evidence of inequity of access by age and sex.
      The most suitable option identified in the option appraisal was a bone
      densitometry service based in the central location of Llandudno. CONCLUSION: The
      assessment identified significant unmet need for DXA scanning. A recommendation
      was made to improve access through the introduction of a new bone densitometry
      service based at Llandudno. This would double scanning provision provided and
      reduce travel costs and time for many North Wales residents. This recommendation
      was adopted by a joint commissioning group established by the six Local Health
      Boards in North Wales at the end of 2004 - evidence based commissioning in
      practice.

PMID- 17233894
TI  - Construction and characterization of new piggyBac vectors for constitutive or
      inducible expression of heterologous gene pairs and the identification of a
      previously unrecognized activator sequence in piggyBac.
AB  - BACKGROUND: We constructed and characterized several new piggyBac vectors to
      provide transposition of constitutively- or inducibly-expressible heterologous
      gene pairs. The dual constitutive control element consists of back-to-back copies
      of a baculovirus immediate early (ie1) promoter separated by a baculovirus
      enhancer (hr5). The dual inducible control element consists of back-to-back
      copies of a minimal cytomegalovirus (CMVmin) promoter separated by a synthetic
      operator (TetO7), which drives transcription in the presence of a mutant
      transcriptional repressor plus tetracycline. RESULTS: Characterization of these
      vectors revealed an unexpected position effect, in which heterologous genes
      adjacent to the 3'- terminal region ("rightward" genes) were consistently
      expressed at higher levels than those adjacent to the 5'-terminal region
      ("leftward" genes) of the piggyBac element. This position effect was observed
      with all six heterologous genes examined and with both transcriptional control
      elements. Further analysis demonstrated that this position effect resulted from
      stimulation of rightward gene expression by the internal domain sequence of the
      3'-terminal region of piggyBac. Inserting a copy of this sequence into the 5'-
      terminal repeat region of our new piggyBac vectors in either orientation
      stimulated leftward gene expression. Representative piggyBac vectors designed for
      constitutive or inducible expression of heterologous gene pairs were shown to be
      functional as insect transformation vectors. CONCLUSION: This study is
      significant because (a) it demonstrates the utility of a strategy for the
      construction of piggyBac vectors that can provide constitutive or inducible
      heterologous gene pair expression and (b) it reveals the presence of a previously
      unrecognized transcriptional activator in piggyBac, which is an important and
      increasingly utilized transposable element.

PMID- 17233895
TI  - Intracranial pressure monitoring in intensive care: clinical advantages of a
      computerized system over manual recording.
AB  - INTRODUCTION: The presence of intracranial hypertension (HICP) after traumatic
      brain injury (TBI) affects patient outcome. Intracranial pressure (ICP) data from
      electronic monitoring equipment are usually calculated and recorded hourly in the
      clinical chart by trained nurses. Little is known, however, about how precisely
      this method reflects the real patterns of ICP after severe TBI. In this study, we
      compared hourly manual recording with a validated and continuous computerized
      reference standard. METHODS: Thirty randomly selected patients with severe TBI
      and HICP admitted to the neuroscience intensive care unit (Policlinico University
      Hospital, Milan, Italy) were retrospectively studied. A 24-hour interval with ICP
      monitoring was randomly selected for each patient. The manually recorded data
      available for analysis covered 672 hours corresponding to 36,492 digital data
      points. The two methods were evaluated using the correlation coefficient and the
      Bland and Altman method. We used the proportion test to analyze differences in
      the number of episodes of HICP (ICP > 20 mm Hg) detected with the two methods and
      the paired t test to analyze differences in the percentage of time of HICP.
      RESULTS: There was good agreement between the digitally collected ICP and the
      manual recordings of the end-hour values. Bland and Altman analysis confirmed a
      mean difference between the two methods of 0.05 mm Hg (standard deviation 3.66);
      96% of data were within the limits of agreement (+7.37 and -7.28). The average
      percentages of time of ICP greater than 20 mm Hg were 39% calculated from the
      digital measurements and 34% from the manual observations. From the continuous
      digital recording, we identified 351 episodes of ICP greater than 20 mm Hg
      lasting at least five minutes and 287 similar episodes lasting at least ten
      minutes. Conversely, end-hour ICP of greater than 20 mm Hg was observed in only
      204 cases using manual recording methods. CONCLUSION: Although manually recorded
      end-hour ICP accurately reflected the computerized end-hour and mean hour values,
      the important omission of a number of episodes of high ICP, some of long
      duration, results in a clinical picture that is not accurate or informative of
      the true pattern of unstable ICP in patients with TBI.

PMID- 17233896
TI  - Determining eligibility for antiretroviral therapy in resource-limited settings
      using total lymphocyte counts, hemoglobin and body mass index.
AB  - BACKGROUND: CD4+ T lymphocyte (CD4) cell count testing is the standard method for
      determining eligibility for antiretroviral therapy (ART), but is not widely
      available in sub-Saharan Africa. Total lymphocyte counts (TLCs) have not proven
      sufficiently accurate in identifying subjects with low CD4 counts. We developed
      clinical algorithms using TLCs, hemoglobin (Hb), and body mass index (BMI) to
      identify patients who require ART. METHODS: We conducted a cross-sectional study
      of HIV-infected adults in Uganda, who presented for assessment for ART
      eligibility with WHO clinical stages I, II or III. Two by two tables were
      constructed to examine TLC thresholds, which maximized sensitivity for CD4 cell
      counts <or= 200 cells microL, while minimizing the number offered ART with counts
      > 350 cells microL. Hb and BMI values were then examined to try to improve model
      performance. RESULTS: 1787 subjects were available for analysis. Median CD4 cell
      counts and TLCs, were 239 cells/microL and 1830 cells/microL, respectively.
      Offering ART to all subjects with a TLCs <or= 2250 cells/microL produced a
      sensitivity of 0.88 and a false positive ratio of 0.21. Algorithms that treated
      all patients with a TLC <2000 cells/microL, excluded all patients with a TLC
      >3000 cells/microL, and used Hb and/or BMI values to determine eligibility for
      those with TLC values between 2000 and 3000 cells/microL, marginally improved
      accuracy. CONCLUSION: TLCs appear useful in predicting who would be eligible for
      ART based on CD4 cell count criteria. Hb and BMI values may be useful in
      prioritizing patients for ART, but did not improve model accuracy.

PMID- 17233897
TI  - A novel BRCA-1 mutation in Arab kindred from east Jerusalem with breast and
      ovarian cancer.
AB  - BACKGROUND: The incidence of breast cancer (BC) in Arab women is lower compared
      to the incidence in the Jewish population in Israel; still, it is the most common
      malignancy among Arab women. There is a steep rise in breast cancer incidence in
      the Arab population in Israel over the last 10 years that can be attributed to
      life style changes. But, the younger age of BC onset in Arab women compared with
      that of the Jewish population is suggestive of a genetic component in BC
      occurrence in that population. METHODS: We studied the family history of 31 women
      of Palestinian Arab (PA) origin affected with breast (n = 28), ovarian (n = 3)
      cancer. We used denaturing high performance liquid chromatography (DHPLC) to
      screen for mutations of BRCA1/2 in 4 women with a personal and family history
      highly suggestive of genetic predisposition. RESULTS: A novel BRCA1 mutation,
      E1373X in exon 12, was found in a patient affected with ovarian cancer. Four of
      her family members, 3 BC patients and a healthy individual were consequently also
      found to carry this mutation. Of the other 27 patients, which were screened for
      this specific mutation none was found to carry it. CONCLUSION: We found a novel
      BRCA1 mutation in a family of PA origin with a history highly compatible with
      BRCA1 phenotype. This mutation was not found in additional 30 PA women affected
      with BC or OC. Therefore full BRCA1/2 screening should be offered to patients
      with characteristic family history. The significance of the novel BRCA1 mutation
      we identified should be studied in larger population. However, it is likely that
      the E1373X mutation is not a founder frequent mutation in the PA population.

PMID- 17233898
TI  - A long-term "memory" of HIF induction in response to chronic mild decreased
      oxygen after oxygen normalization.
AB  - BACKGROUND: Endothelial dysfunction (ED) is functionally characterized by
      decreased vasorelaxation, increased thrombosis, increased inflammation, and
      altered angiogenic potential, has been intimately associated with the progression
      and severity of cardiovascular disease. Patients with compromised cardiac
      function oftentimes have a state of chronic mild decreased oxygen at the level of
      the vasculature and organs, which has been shown to exacerbate ED. Hypoxia
      inducible factor (HIF) is a transcription factor complex shown to be the master
      regulator of the cellular response to decreased oxygen levels and many HIF target
      genes have been shown to be associated with ED. METHODS: Human endothelial and
      aortic smooth muscle cells were exposed either to A) normoxia (21% O2) for three
      weeks, or to B) mild decreased oxygen (15% O2) for three weeks to mimic blood
      oxygen levels in patients with heart failure, or to C) mild decreased oxygen for
      two weeks followed by one week of normoxia ("memory" treatment). Levels of HIF
      signaling genes (HIF-1alpha, HIF-2alpha, VEGF, BNIP3, GLUT-1, PAI-1 and iNOS)
      were measured both at the protein and mRNA levels. RESULTS: It was found that
      chronic exposure to mild decreased oxygen resulted in significantly increased HIF
      signaling. There was also a "memory" of HIF-1alpha and HIF target gene induction
      when oxygen levels were normalized for one week, and this "memory" could be
      interrupted by adding a small molecule HIF inhibitor to the last week of
      normalized oxygen. Finally, levels of ubiquitylated HIF-1alpha were reduced in
      response to chronic mild decreased oxygen and were not full restored after oxygen
      normalization. CONCLUSION: These data suggest that HIF signaling may be
      contributing to the pathogenesis of endothelial dysfunction and that
      normalization of oxygen levels may not be enough to reduce vascular stress.

PMID- 17233899
TI  - Integration of regulatory signals through involvement of multiple global
      regulators: control of the Escherichia coli gltBDF operon by Lrp, IHF, Crp, and
      ArgR.
AB  - BACKGROUND: The glutamate synthase operon (gltBDF) contributes to one of the two
      main pathways of ammonia assimilation in Escherichia coli. Of the seven most
      global regulators, together affecting expression of about half of all E. coli
      genes, two were previously shown to exert direct, positive control on gltBDF
      transcription: Lrp and IHF. The involvement of Lrp is unusual in two respects:
      first, it is insensitive to the usual coregulator leucine, and second, Lrp binds
      more than 150 bp upstream of the transcription starting point. There was indirect
      evidence for involvement of a third global regulator, Crp. Given the
      physiological importance of gltBDF, and the potential opportunity to learn about
      integration of global regulatory signals, a combination of in vivo and in vitro
      approaches was used to investigate the involvement of additional regulatory
      proteins, and to determine their relative binding positions and potential
      interactions with one another and with RNA polymerase (RNAP). RESULTS: Crp and a
      more local regulator, ArgR, directly control gltBDF transcription, both acting
      negatively. Crp-cAMP binds a sequence centered at -65.5 relative to the
      transcript start. Mutation of conserved nucleotides in the Crp binding site
      abolishes the Crp-dependent repression. ArgR also binds to the gltBDF promoter
      region, upstream of the Lrp binding sites, and decreases transcription. RNAP only
      yields a defined DNAse I footprint under two tested conditions: in the presence
      of both Lrp and IHF, or in the presence of Crp-cAMP. The DNAse I footprint of
      RNAP in the presence of Lrp and IHF is altered by ArgR. CONCLUSION: The
      involvement of nearly half of E. coli's most-global regulatory proteins in the
      control of gltBDF transcription is striking, but seems consistent with the
      central metabolic role of this operon. Determining the mechanisms of activation
      and repression for gltBDF was beyond the scope of this study. However the results
      are consistent with a model in which IHF bends the DNA to allow stabilizing
      contacts between Lrp and RNAP, ArgR interferes with such contacts, and Crp
      introduces an interfering bend in the DNA and/or stabilizes RNAP in a poised but
      inactive state.

PMID- 17233900
TI  - Text-derived concept profiles support assessment of DNA microarray data for acute
      myeloid leukemia and for androgen receptor stimulation.
AB  - BACKGROUND: High-throughput experiments, such as with DNA microarrays, typically
      result in hundreds of genes potentially relevant to the process under study,
      rendering the interpretation of these experiments problematic. Here, we propose
      and evaluate an approach to find functional associations between large numbers of
      genes and other biomedical concepts from free-text literature. For each gene, a
      profile of related concepts is constructed that summarizes the context in which
      the gene is mentioned in literature. We assign a weight to each concept in the
      profile based on a likelihood ratio measure. Gene concept profiles can then be
      clustered to find related genes and other concepts. RESULTS: The experimental
      validation was done in two steps. We first applied our method on a controlled
      test set. After this proved to be successful the datasets from two DNA microarray
      experiments were analyzed in the same way and the results were evaluated by
      domain experts. The first dataset was a gene-expression profile that
      characterizes the cancer cells of a group of acute myeloid leukemia patients. For
      this group of patients the biological background of the cancer cells is largely
      unknown. Using our methodology we found an association of these cells to
      monocytes, which agreed with other experimental evidence. The second data set
      consisted of differentially expressed genes following androgen receptor
      stimulation in a prostate cancer cell line. Based on the analysis we put forward
      a hypothesis about the biological processes induced in these studied cells:
      secretory lysosomes are involved in the production of prostatic fluid and their
      development and/or secretion are androgen-regulated processes. CONCLUSION: Our
      method can be used to analyze DNA microarray datasets based on information
      explicitly and implicitly available in the literature. We provide a publicly
      available tool, dubbed Anni, for this purpose.

PMID- 17233901
TI  - Identification of candidate genes associated with cell wall digestibility and
      eQTL (expression quantitative trait loci) analysis in a Flint x Flint maize
      recombinant inbred line population.
AB  - BACKGROUND: Cell-wall digestibility is the major target for improving the feeding
      value of forage maize. An understanding of the molecular basis for cell-wall
      digestibility is crucial towards breeding of highly digestible maize. RESULTS:
      865 candidate ESTs for cell-wall digestibility were selected according to the
      analysis of expression profiles in 1) three sets of brown-midrib isogenic lines
      in the genetic background of inbreds 1332 (1332 and 1332 bm3), 5361 (5361 and
      5361 bm3), and F2 (F2, F2 bm1, F2 bm2, and F2 bm3), 2) the contrasting extreme
      lines of FD (Flint x Dent, AS08 x AS 06), DD1 (Dent x Dent, AS11 x AS09), and DD2
      (Dent x Dent, AS29 x AS30) mapping populations, and 3) two contrasting isogenic
      inbreds, AS20 and AS21. Out of those, 439 ESTs were assembled on our "Forage
      Quality Array", a small microarray specific for cell wall digestibility related
      experiments. Transcript profiles of 40 lines of a Flint x Flint population were
      monitored using the Forage Quality Array, which were contrasting for cell wall
      digestibility. Using t-tests (p < 0.01), the expression patterns of 102 ESTs were
      significantly different between high and low quality groups. Using interval
      mapping, eQTL (LOD > or = 2.4) were detected for 20% (89 of 439) of the spotted
      ESTs. On average, these eQTL explained 39% of the transcription variation of the
      corresponding ESTs. Only 26% (23 of 89) ESTs detected a single eQTL. eQTL
      hotspots, containing greater than 5% of the total number of eQTL, were located in
      chromosomal bins 1.07, 1.12, 3.05, 8.03, and 9.04, respectively. Bin 3.05 was co
      localized with a cell-wall digestibility related QTL cluster. CONCLUSION: 102
      candidate genes for cell-wall digestibility were validated by genetical genomics
      approach. Although the cDNA array highlights gene types (the tested gene and any
      close family members), trans-acting factors or metabolic bottlenecks seem to play
      the major role in controlling heritable variation of gene expression related to
      cell-wall digestibility, since no in silico mapped ESTs were in the same location
      as their own eQTL. Transcriptional variation was generally found to be oligogenic
      rather than monogenic inherited due to only 26% ESTs detected a single eQTL in
      the present study. One eQTL hotspot was co-localized with cell wall digestibility
      related QTL cluster on bins 3.05, implying that in this case the gene(s)
      underlying QTL and eQTL are identical. As the field of genetical genomics
      develops, it is expected to significantly improve our knowledge about complex
      traits, such as cell wall degradability. Comprehensive knowledge of the lignin
      pathway and cell wall biogenesis will allow plant breeders to choose the best
      genomic targets controlling these characters, for improving forage digestibility
      through genetic engineering or marker-assisted selection.

PMID- 17233902
TI  - Cholesterol synthesis inhibitors protect against platelet-activating factor
      induced neuronal damage.
AB  - BACKGROUND: Platelet-activating factor (PAF) is implicated in the neuronal damage
      that accompanies ischemia, prion disease and Alzheimer's disease (AD). Since some
      epidemiological studies demonstrate that statins, drugs that reduce cholesterol
      synthesis, have a beneficial effect on mild AD, we examined the effects of two
      cholesterol synthesis inhibitors on neuronal responses to PAF. METHODS: Primary
      cortical neurons were treated with cholesterol synthesis inhibitors (simvastatin
      or squalestatin) prior to incubation with different neurotoxins. The effects of
      these drugs on neuronal cholesterol levels and neuronal survival were measured.
      Immunoblots were used to determine the effects of simvastatin or squalestatin on
      the distribution of the PAF receptor and an enzyme linked immunoassay was used to
      quantify the amounts of PAF receptor. RESULTS: PAF killed primary neurons in a
      dose-dependent manner. Pre-treatment with simvastatin or squalestatin reduced
      neuronal cholesterol and increased the survival of PAF-treated neurons. Neuronal
      survival was increased 50% by 100 nM simvastatin, or 20 nM squalestatin. The
      addition of mevalonate restored cholesterol levels, and reversed the protective
      effect of simvastatin. Simvastatin or squalestatin did not affect the amounts of
      the PAF receptor but did cause it to disperse from within lipid rafts.
      CONCLUSION: Treatment of neurons with cholesterol synthesis inhibitors including
      simvastatin and squalestatin protected neurons against PAF. Treatment caused a
      percentage of the PAF receptors to disperse from cholesterol-sensitive domains.
      These results raise the possibility that the effects of statins on
      neurodegenerative disease are, at least in part, due to desensitisation of
      neurons to PAF.

PMID- 17233903
TI  - Transcriptional changes associated with breast cancer occur as normal human
      mammary epithelial cells overcome senescence barriers and become immortalized.
AB  - BACKGROUND: Human mammary epithelial cells (HMEC) overcome two well-characterized
      genetic and epigenetic barriers as they progress from primary cells to fully
      immortalized cell lines in vitro. Finite lifespan HMEC overcome an Rb-mediated
      stress-associated senescence barrier (stasis), and a stringent, telomere-length
      dependent, barrier (agonescence or crisis, depending on p53 status). HMEC that
      have overcome the second senescence barrier are immortalized. METHODS: We have
      characterized pre-stasis, post-selection (post-stasis, with p16 silenced), and
      fully immortalized HMEC by transcription profiling and RT-PCR. Four pre-stasis
      and seven post-selection HMEC samples, along with 10 representatives of fully
      immortalized breast epithelial cell lines, were profiled using Affymetrix U133A/B
      chips and compared using both supervised and unsupervised clustering. Datasets
      were validated by RT-PCR for a select set of genes. Quantitative
      immunofluorescence was used to assess changes in transcriptional regulators
      associated with the gene expression changes. RESULTS: The most dramatic and
      uniform changes we observed were in a set of about 30 genes that are
      characterized as a "cancer proliferation cluster," which includes genes expressed
      during mitosis (CDC2, CDC25, MCM2, PLK1) and following DNA damage. The increased
      expression of these genes was particularly concordant in the fully immortalized
      lines. Additional changes were observed in IFN-regulated genes in some post
      selection and fully immortalized cultures. Nuclear localization was observed for
      several transcriptional regulators associated with expression of these genes in
      post-selection and immortalized HMEC, including Rb, Myc, BRCA1, HDAC3 and SP1.
      CONCLUSION: Gene expression profiles and cytological changes in related
      transcriptional regulators indicate that immortalized HMEC resemble non-invasive
      breast cancers, such as ductal and lobular carcinomas in situ, and are strikingly
      distinct from finite-lifespan HMEC, particularly with regard to genes involved in
      proliferation, cell cycle regulation, chromosome structure and the DNA damage
      response. The comparison of HMEC profiles with lines harboring oncogenic changes
      (e.g. overexpression of Her-2neu, loss of p53 expression) identifies genes
      involved in tissue remodeling as well as proinflamatory cytokines and S100
      proteins. Studies on carcinogenesis using immortalized cell lines as starting
      points or "normal" controls need to account for the significant pre-existing
      genetic and epigenetic changes inherent in such lines before results can be
      broadly interpreted.

PMID- 17233904
TI  - Five-year predictors of physical activity decline among adults in low-income
      communities: a prospective study.
AB  - BACKGROUND: Obesity in North America is now endemic, and increased understanding
      of the determinants of physical inactivity is critical. This analysis identified
      predictors of declines in physical activity over 5 years among adults in low
      income, inner-city neighbourhoods. METHODS: Data on leisure time physical
      activity were collected in telephone interviews in 1992 and 1997 from 765 adults
      (47% of baseline respondents), as part of the evaluation of a community-based
      cardiovascular disease risk reduction program. RESULTS: One-third of 527
      participants who were physically active at baseline, were inactive in 1997.
      Predictors of becoming inactive included female sex (OR = 1.63 95% CI (1.09,
      2.43)), older age (1.02 (1.01, 1.04)), higher BMI (1.57 (1.03, 2.40)), poor self
      rated health (1.39 (1.05, 1.84)), lower self-efficacy for physical activity (1.46
      (1.00, 2.14)), and not using a neighborhood facility for physical activity (1.61
      (1.02, 2.14)). CONCLUSION: These results highlight the fact that a variety of
      variables play a role in determining activity level, from demographic variables
      such as age and sex, to psychosocial and environmental variables. In addition,
      these results highlight the important role that other health-related variables
      may play in predicting physical activity level, in particular the observed
      association between baseline BMI and the increased risk of becoming inactive over
      time. Lastly, these results demonstrate the need for multi-component
      interventions in low-income communities, which target a range of issues, from
      psychosocial factors, to features of the physical environment.

PMID- 17233905
TI  - Inventing an arsenal: adaptive evolution and neofunctionalization of snake venom
      phospholipase A2 genes.
AB  - BACKGROUND: Gene duplication followed by functional divergence has long been
      hypothesized to be the main source of molecular novelty. Convincing examples of
      neofunctionalization, however, remain rare. Snake venom phospholipase A2 genes
      are members of large multigene families with many diverse functions, thus they
      are excellent models to study the emergence of novel functions after gene
      duplications. RESULTS: Here, I show that positive Darwinian selection and
      neofunctionalization is common in snake venom phospholipase A2 genes. The pattern
      of gene duplication and positive selection indicates that adaptive molecular
      evolution occurs immediately after duplication events as novel functions emerge
      and continues as gene families diversify and are refined. Surprisingly, adaptive
      evolution of group-I phospholipases in elapids is also associated with speciation
      events, suggesting adaptation of the phospholipase arsenal to novel prey species
      after niche shifts. Mapping the location of sites under positive selection onto
      the crystal structure of phospholipase A2 identified regions evolving under
      diversifying selection are located on the molecular surface and are likely
      protein-protein interactions sites essential for toxin functions. CONCLUSION:
      These data show that increases in genomic complexity (through gene duplications)
      can lead to phenotypic complexity (venom composition) and that positive Darwinian
      selection is a common evolutionary force in snake venoms. Finally, regions
      identified under selection on the surface of phospholipase A2 enzymes are
      potential candidate sites for structure based antivenin design.

PMID- 17233906
TI  - Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on
      malignant melanoma cells.
AB  - BACKGROUND: Malignant melanoma is one of the most aggressive skin cancer and
      chemotherapeutic agents currently in use are still unsatisfactory. Prevention and
      early diagnosis are the only effective tools against this tumour whose incidence
      and mortality rates are highly increased during the last decades in fair skin
      populations. Therefore the search for novel therapeutic approaches is warranted.
      Aim of this work was to identify and test new compounds with antiproliferative
      and cytotoxic activity on melanoma cells. We tested eugenol together with six
      natural and synthetic eugenol-related compounds for their capability to inhibit
      cell growth on primary melanoma cell lines established from patients' tissue
      samples. RESULTS: Eugenol and isoeugenol monomers and their respective O
      methylated forms did not show to inhibit melanoma cells proliferation.
      Conversely, the dimeric forms (biphenyls) showed some antiproliferative activity
      which was mild for dehydrodieugenol, higher for its O,O'-methylated form (O,O'
      dimethyl-dehydrodieugenol), and markedly pronounced for the racemic mixture of
      the brominated biphenyl (6,6'-dibromo-dehydrodieugenol) (S7), being its
      enantiomeric form (S) the most effective compared to the other compounds. Such
      activity resulted to be selective against tumour cells, without affecting
      cultured normal human skin fibroblasts. Dose and time dependence curves have been
      obtained for the enantiomeric form S7-(S). Then IC50 and minimal effective doses
      and times have been established for the melanoma cell lines tested. TUNEL and
      phosphatidylserine exposure assays demonstrated the occurrence of apoptotic
      events associated with the antiproliferative activity of S7-(S). Cytotoxic
      activity and apoptosis induced by treating melanoma cells with eugenol-related
      biphenyls was partially dependent by caspase activation. CONCLUSION: Our findings
      demonstrate that the eugenol related biphenyl (S)-6,6'-dibromo-dehydrodieugenol
      elicits specific antiproliferative activity on neuroectodermal tumour cells
      partially triggering apoptosis and its activity should be further investigated on
      in vivo melanoma models in order to evaluate the real anticancer effectiveness on
      such tumour.

PMID- 17233907
TI  - Systematic analysis of the regulation of type three secreted effectors in
      Salmonella enterica serovar Typhimurium.
AB  - BACKGROUND: The type III secretion system (TTSS) is an important virulence
      determinant of Gram-negative bacterial pathogens. It enables the injection of
      effector proteins into the cytosol of eukaryotic cells. These effectors
      ultimately manipulate the cellular functions of the infected organism. Salmonella
      enterica serovar Typhimurium encodes two virulence associated TTSSs encoded by
      the Salmonella Pathogenicity Islands (SPI) 1 and 2 that are required for the
      intestinal and systemic phases of the infection, respectively. However, recent
      studies suggest that the roles of these TTSSs are not restricted to these
      compartments. The regulation of TTSSs in Salmonella is very complex with several
      regulators operating to activate or to repress expression depending on the
      environmental conditions. RESULTS: We performed a systematic analysis of the
      regulation of type III effectors during growth in vitro. We have tested the
      ability of seven regulatory genes to regulate ten effector genes. Each regulator
      was expressed in the absence of the other six to avoid cascade effects. Our
      results confirm and extend the previously reported regulation of TTSS1 and TTSS2
      effectors by InvF-SicA and SsrB respectively. CONCLUSION: The set of strains
      constructed for this study can be used to quickly and systematically study the
      regulation of newly identified effector genes of Salmonella enterica. The
      approach we have used can also be applied to study complex regulatory cascades in
      other bacterial species.

PMID- 17233908
TI  - AYUMS: an algorithm for completely automatic quantitation based on LC-MS/MS
      proteome data and its application to the analysis of signal transduction.
AB  - BACKGROUND: Comprehensive description of the behavior of cellular components in a
      quantitative manner is essential for systematic understanding of biological
      events. Recent LC-MS/MS (tandem mass spectrometry coupled with liquid
      chromatography) technology, in combination with the SILAC (Stable Isotope
      Labeling by Amino acids in Cell culture) method, has enabled us to make relative
      quantitation at the proteome level. The recent report by Blagoev et al. (Nat.
      Biotechnol., 22, 1139-1145, 2004) indicated that this method was also applicable
      for the time-course analysis of cellular signaling events. Relative quatitation
      can easily be performed by calculating the ratio of peak intensities
      corresponding to differentially labeled peptides in the MS spectrum. As currently
      available software requires some GUI applications and is time-consuming, it is
      not suitable for processing large-scale proteome data. RESULTS: To resolve this
      difficulty, we developed an algorithm that automatically detects the peaks in
      each spectrum. Using this algorithm, we developed a software tool named AYUMS
      that automatically identifies the peaks corresponding to differentially labeled
      peptides, compares these peaks, calculates each of the peak ratios in mixed
      samples, and integrates them into one data sheet. This software has enabled us to
      dramatically save time for generation of the final report. CONCLUSION: AYUMS is a
      useful software tool for comprehensive quantitation of the proteome data
      generated by LC-MS/MS analysis. This software was developed using Java and runs
      on Linux, Windows, and Mac OS X. Please contact ayums@ims.u-tokyo.ac.jp if you
      are interested in the application. The project web page is
      http://www.csml.org/ayums/.

PMID- 17233910
TI  - Multicenter randomized trial of cell therapy in cardiopathies - MiHeart Study.
AB  - BACKGROUND: Cardiovascular diseases are the major cause of death in the world.
      Current treatments have not been able to reverse this scenario, creating the need
      for the development of new therapies. Cell therapies have emerged as an
      alternative for cardiac diseases of distinct causes in experimental animal
      studies and more recently in clinical trials. METHOD/DESIGN: We have designed
      clinical trials to test for the efficacy of autologous bone marrow derived
      mononuclear cell therapies in four different cardiopathies: acute and chronic
      ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are
      multicenter, randomized, double-blind and placebo controlled. In each trial 300
      patients will be enrolled and receive optimized therapy for their specific
      condition. Additionally, half of the patients will receive the autologous bone
      marrow cells while the other half will receive placebo (saline with 5% autologous
      serum). For each trial there are specific inclusion and exclusion criteria and
      the method for cell delivery is intramyocardial for the chronic ischemic heart
      disease and intracoronary for all others. Primary endpoint for all studies will
      be the difference in ejection fraction (determined by Simpson's rule) six and
      twelve months after intervention in relation to the basal ejection fraction. The
      main hypothesis of this study is that the patients who receive the autologous
      bone-marrow stem cell implant will have after a 6 month follow-up a mean increase
      of 5% in absolute left ventricular ejection fraction in comparison with the
      control group. DISCUSSION: Many phase I clinical trials using cell therapy for
      cardiac diseases have already been performed. The few randomized studies have
      yielded conflicting results, rendering necessary larger well controlled trials to
      test for efficacy of cell therapies in cardiopathies. The trials registration
      numbers at the NIH registry are the following: Chagasic cardiomyopathy
      (NCT00349271), dilated cardiomyopathy (NCT00333827), acute myocardial infarction
      (NCT00350766) and Chronic Ischemic Heart Disease (NCT00362388).

PMID- 17233909
TI  - Differential role of ICAM ligands in determination of human memory T cell
      differentiation.
AB  - BACKGROUND: Leukocyte Function Antigen-1 (LFA-1) is a primary adhesion molecule
      that plays important roles in T cell activation, leukocyte recirculation, and
      trans-endothelial migration. By applying a multivariate intracellular phospho
      proteomic analysis, we demonstrate that LFA-1 differentially activates signaling
      molecules. RESULTS: Signal intensity was dependent on both ICAM ligand and LFA-1
      concentration. In the presence of CD3 and CD28 stimulation, ICAM-2 and ICAM-3
      decreased TGFbeta1 production more than ICAM-1. In long-term differentiation
      experiments, stimulation with ICAM-3, CD3, and CD28 generated IFNgamma producing
      CD4+CD45RO+CD62L-CD11aBrightCD27- cells that had increased expression of
      intracellular BCL2, displayed distinct chemokine receptor profiles, and exhibited
      distinct migratory characteristics. Only CD3/CD28 with ICAM-3 generated
      CD4+CD45RO+CD62L-CD11aBrightCD27- cells that were functionally responsive to
      chemotaxis and exhibited higher frequencies of cells that signaled to JNK and
      ERK1/2 upon stimulation with MIP3alpha. Furthermore, these reports identify that
      the LFA-1 receptor, when presented with multiple ligands, can result in distinct
      T cell differentiation states and suggest that the combinatorial integration of
      ICAM ligand interactions with LFA-1 have functional consequences for T cell
      biology. CONCLUSION: Thus, the ICAM ligands, differentially modulate LFA-1
      signaling in T cells and potentiate the development of memory human T cells in
      vitro. These findings are of importance in a mechanistic understanding of memory
      cell differentiation and ex vivo generation of memory cell subsets for
      therapeutic applications.

PMID- 17233911
TI  - Novel dexamethasone-HPMA copolymer conjugate and its potential application in
      treatment of rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology.
      Effective treatment of this disorder has been hampered by the lack of
      availability of agents that selectively target affected joint tissue. We
      developed a novel pH-sensitive drug delivery system of dexamethasone (Dex) based
      on an N-(2-hydroxypropyl)methacrylamide copolymer (P-Dex) and have shown that the
      delivery system specifically accumulates in inflamed joints in an animal model of
      arthritis. We hypothesize that the arthrotropism of the delivery system and the
      local acidosis-mediated drug release provide superior therapeutic efficacy and
      potentially reduced side effects in RA treatment. The initial in vitro drug
      release study confirmed that the Dex release is indeed dependent upon the
      environmental pH. At pH 5, 37 degrees C, the conjugate shows the highest level of
      drug release. When administered systemically in an adjuvant-induced arthritis rat
      model, P-Dex offers superior and longer-lasting anti-inflammatory effects
      compared with systemically administered free Dex. In addition, greater bone and
      cartilage preservation was observed with the P-Dex treatment compared with free
      Dex treatment. Our data indicate that the differential effect of the conjugate is
      related to its selective accumulation, potential macrophage-mediated retention,
      and pH-sensitive drug release (extracellular and intracellular) in arthritic
      joints. This newly developed drug delivery system provides a unique method for
      selective targeting of glucocorticoids to inflamed joints which may potentially
      reduce systemic side effects.

PMID- 17233912
TI  - The clinimetric qualities of patient-assessed instruments for measuring chronic
      ankle instability: a systematic review.
AB  - BACKGROUND: The assessment of outcomes from the patient's perspective becomes
      more recognized in health care. Also in patients with chronic ankle instability,
      the degree of present impairments, disabilities and participation problems should
      be documented from the perspective of the patient. The decision about which
      patient-assessed instrument is most appropriate for clinical practice should be
      based upon systematic reviews. Only rating scales constructed for patients with
      acute ligament injuries were systematically reviewed in the past. The aim of this
      study was to review systematically the clinimetric qualities of patient-assessed
      instruments designed for patients with chronic ankle instability. METHODS: A
      computerized literature search of Medline, Embase, Cinahl, Web of Science, Sport
      Discus and the Cochrane Controlled Trial Register was performed to identify
      eligible instruments. Two reviewers independently evaluated the clinimetric
      qualities of the selected instruments using a criteria list. The inter-observer
      reliability of both the selection procedure and the clinimetric evaluation was
      calculated using modified kappa coefficients. RESULTS: The inter-observer
      reliability of the selection procedure was excellent (k = .86). Four instruments
      met the eligibility criteria: the Ankle Joint Functional Assessment Tool (AJFAT),
      the Functional Ankle Outcome Score (FAOS), the Foot and Ankle Disability Index
      (FADI) and the Functional Ankle Ability Measure (FAAM). The inter-observer
      reliability of the quality assessment was substantial to excellent (k between .64
      and .88). Test-retest reliability was demonstrated for the FAOS, the FADI and the
      FAAM but not for the AJFAT. The FAOS and the FAAM met the criteria for content
      validity and construct validity. For none of the studied instruments, the
      internal consistency was sufficiently demonstrated. The presence of floor- and
      ceiling effects was assessed for the FAOS but ceiling effects were present for
      all subscales. Responsiveness was demonstrated for the AJFAT, FADI and the FAAM.
      Only for the FAAM, a minimal clinical important difference (MCID) was presented.
      CONCLUSION: The FADI and the FAAM can be considered as the most appropriate,
      patient-assessed tools to quantify functional disabilities in patients with
      chronic ankle instability. The clinimetric qualities of the FAAM need to be
      further demonstrated in a specific population of patients with chronic ankle
      instability.

PMID- 17233913
TI  - Effects of bone marrow cell transplant on thyroid function in an I131-induced low
      T4 and elevated TSH rat model.
AB  - BACKGROUND: We developed a study using low dose radioactive iodine creating an
      animal model of transient elevation of thyroid stimulating hormone (TSH). Male
      derived bone marrow cells were transplanted to asses their effect on thyroid
      function and their capability to repair the thyroid parenchyma. RESULTS: At 40 an
      80 days after I131 treatment, the study groups TSH and T4 serum values both
      increased and decreased significantly respectively compared to the negative
      control group. Eight weeks after cell transplantation, neither TSH nor T4 showed
      a significant difference in any group. The mean number of SRY gene copies found
      in group I (Left Intracardiac Transplant) was 523.3 and those in group II
      (Intrathyroid Transplant) were only 73. Group III (No Transplant) and IV had no
      copies. Group I presented a partial restore of the histological pattern of rat
      thyroid with approximately 20%-30% of normal-sized follicles. Group II did not
      show any histological differences compared to group III (Positive control).
      CONCLUSION: Both a significant increase of TSH and decrease of T4 can be induced
      as early as day 40 after a low dose of I131 in rats. Restore of normal thyroid
      function can be spontaneously achieved after using a low dose RAI in a rat model.
      The use of BM derived cells did not affect the re-establishment of thyroid
      function and might help restore the normal architecture after treatment with RAI.

PMID- 17233916
TI  - Multivariate analysis and visualization of splicing correlations in single-gene
      transcriptomes.
AB  - BACKGROUND: RNA metabolism, through 'combinatorial splicing', can generate
      enormous structural diversity in the proteome. Alternative domains may interact,
      however, with unpredictable phenotypic consequences, necessitating integrated RNA
      level regulation of molecular composition. Splicing correlations within
      transcripts of single genes provide valuable clues to functional relationships
      among molecular domains as well as genomic targets for higher-order splicing
      regulation. RESULTS: We present tools to visualize complex splicing patterns in
      full-length cDNA libraries. Developmental changes in pair-wise correlations are
      presented vectorially in 'clock plots' and linkage grids. Higher-order
      correlations are assessed statistically through Monte Carlo analysis of a log
      linear model with an empirical-Bayes estimate of the true probabilities of
      observed and unobserved splice forms. Log-linear coefficients are visualized in a
      'spliceprint,' a signature of splice correlations in the transcriptome. We
      present two novel metrics: the linkage change index, which measures the
      directional change in pair-wise correlation with tissue differentiation, and the
      accuracy index, a very simple goodness-of-fit metric that is more sensitive than
      the integrated squared error when applied to sparsely populated tables, and
      unlike chi-square, does not diverge at low variance. Considerable attention is
      given to sparse contingency tables, which are inherent to single-gene libraries.
      CONCLUSION: Patterns of splicing correlations are revealed, which span a broad
      range of interaction order and change in development. The methods have a broad
      scope of applicability, beyond the single gene--including, for example, multiple
      gene interactions in the complete transcriptome.

PMID- 17233914
TI  - Shared as well as distinct roles of EHD proteins revealed by biochemical and
      functional comparisons in mammalian cells and C. elegans.
AB  - BACKGROUND: The four highly homologous human EHD proteins (EHD1-4) form a
      distinct subfamily of the Eps15 homology domain-containing protein family and are
      thought to regulate endocytic recycling. Certain members of this family have been
      studied in different cellular contexts; however, a lack of concurrent analyses of
      all four proteins has impeded an appreciation of their redundant versus distinct
      functions. RESULTS: Here, we analyzed the four EHD proteins both in mammalian
      cells and in a cross-species complementation assay using a C. elegans mutant
      lacking the EHD ortholog RME-1. We show that all human EHD proteins rescue the
      vacuolated intestinal phenotype of C. elegans rme-1 mutant, are simultaneously
      expressed in a panel of mammalian cell lines and tissues tested, and variably
      homo- and hetero-oligomerize and colocalize with each other and Rab11, a
      recycling endosome marker. Small interfering RNA (siRNA) knock-down of EHD1, 2
      and 4, and expression of dominant-negative EH domain deletion mutants showed that
      loss of EHD1 and 3 (and to a lesser extent EHD4) but not EHD2 function retarded
      transferrin exit from the endocytic recycling compartment. EH domain deletion
      mutants of EHD1 and 3 but not 2 or 4, induced a striking perinuclear clustering
      of co-transfected Rab11. Knock-down analyses indicated that EHD1 and 2 regulate
      the exit of cargo from the recycling endosome while EHD4, similar to that
      reported for EHD3 (Naslavsky et al. (2006) Mol. Biol. Cell 17, 163), regulates
      transport from the early endosome to the recycling endosome. CONCLUSION:
      Altogether, our studies suggest that concurrently expressed human EHD proteins
      perform shared as well as discrete functions in the endocytic recycling pathway
      and lay a foundation for future studies to identify and characterize the
      molecular pathways involved.

PMID- 17233917
TI  - Identification of novel immunogens in Pasteurella multocida.
AB  - P. multocida is a Gram-negative pathogen responsible for causing diseases in
      animals of economic significance to livestock industries throughout the world.
      Current vaccines include bacterins, which provide only limited protection against
      homologous serotypes. Therefore there is a need for more effective vaccines to
      control diseases caused by P. multocida. As a step towards developing vaccines
      against fowl cholera, a genomics based approach was applied for the
      identification of novel immunogens. RESULTS: Bioinformatics analysis of the P.
      multocida genome predicted 129 proteins as secreted, located in the outer
      membrane, or lipoproteins. 105 of the genes encoding these proteins were cloned
      and recombinant protein expressed in Escherichia coli. Polyclonal serum from P.
      multocida-infected chickens reacted with a subset of these proteins. CONCLUSION:
      These data show the range of bacterial immunogens recognized by the chicken
      immune system, including 6 novel immunoreactive proteins.

PMID- 17233918
TI  - Low dose radiation and cancer in A-bomb survivors: latency and non-linear dose
      response in the 1950-90 mortality cohort.
AB  - BACKGROUND: Analyses of Japanese A-bomb survivors' cancer mortality risks are
      used to establish recommended annual dose limits, currently set at 1 mSv (public)
      and 20 mSv (occupational). Do radiation doses below 20 mSv have significant
      impact on cancer mortality in Japanese A-bomb survivors, and is the dose-response
      linear? METHODS: I analyse stomach, liver, lung, colon, uterus, and all-solid
      cancer mortality in the 0-20 mSv colon dose subcohort of the 1950-90 (grouped)
      mortality cohort, by Poisson regression using a time-lagged colon dose to detect
      latency, while controlling for gender, attained age, and age-at-exposure. I
      compare linear and non-linear models, including one adapted from the cellular
      bystander effect for alpha particles. RESULTS: With a lagged linear model, Excess
      Relative Risk (ERR) for the liver and all-solid cancers is significantly positive
      and several orders of magnitude above extrapolations from the Life Span Study
      Report 12 analysis of the full cohort. Non-linear models are strongly superior to
      the linear model for the stomach (latency 11.89 years), liver (36.90), lung
      (13.60) and all-solid (43.86) in fitting the 0-20 mSv data and show significant
      positive ERR at 0.25 mSv and 10 mSv lagged dose. The slope of the dose-response
      near zero is several orders of magnitude above the slope at high doses.
      CONCLUSION: The standard linear model applied to the full 1950-90 cohort greatly
      underestimates the risks at low doses, which are significant when the 0-20 mSv
      subcohort is modelled with latency. Non-linear models give a much better fit and
      are compatible with a bystander effect.

PMID- 17233919
TI  - Can current national surveillance systems in England and Wales monitor sexual
      transmission of hepatitis C among HIV-infected men who have sex with men?
AB  - BACKGROUND: Recent reports suggest an increase in sexually-transmitted hepatitis
      C infection among HIV-infected men who have sex with men (MSM) in European
      cities. We investigated whether current national surveillance systems in England
      and Wales (E&W) are able to monitor sexual transmission of hepatitis C infection
      among HIV-infected MSM. METHODS: Routine laboratory reports of hepatitis C
      diagnoses and data from sentinel hepatitis C testing surveillance were matched to
      HIV diagnosis reports to determine: (i) the number of MSM diagnosed with HIV and
      hepatitis C (1996-2003); (ii) the number of HIV-diagnosed MSM tested for
      hepatitis C and found to be positive at sentinel sites (2003). RESULTS: (i)
      Between 1996-2003, 38,027 hepatitis C diagnoses were reported; 25,938 (68%) were
      eligible for matching with HIV diagnoses. Thirty-one men (four in London) had
      both a HIV and hepatitis C diagnosis where the only risk was sex with another
      man. Numbers of "co-diagnosed" MSM increased from 0 in 1996 to 14 in 2003. The
      majority of MSM (22/31) tested hepatitis C positive after HIV diagnosis. (ii) Of
      78,058 test results from sentinel hepatitis C testing sites in 2003, 67,712 (87%)
      were eligible for matching with HIV diagnoses. We identified 242 HIV-diagnosed
      MSM who did not inject drugs who tested for hepatitis C in 2003; 11 (4.5%) tested
      hepatitis C positive (95% CI: 2.3%-8.0%). Applying this percentage to all MSM
      seen for HIV-related care in E&W in 2003, an estimated 680 MSM living with
      diagnosed HIV would have tested positive for sexually-transmitted hepatitis C
      (95% CI: 346-1208). CONCLUSION: Matching routine laboratory reports of hepatitis
      C diagnoses with HIV diagnoses only identified 31 HIV infected MSM with sexually
      transmitted hepatitis C infection. Clinical studies suggest that this is an
      underestimate. On the other hand, matching sentinel surveillance reports with HIV
      diagnoses revealed that in E&W in 2003 nearly 5% of HIV-diagnosed MSM tested
      hepatitis C positive where the only risk was sex with another man. Reports of
      sexually-transmitted hepatitis C infection were not confined to London. Enhanced
      surveillance is needed to monitor sexually-transmitted hepatitis C among HIV
      infected MSM in E&W.

PMID- 17233920
TI  - Comparative genomics reveals a constant rate of origination and convergent
      acquisition of functional retrogenes in Drosophila.
AB  - BACKGROUND: Processed copies of genes (retrogenes) are duplicate genes that
      originated through the reverse-transcription of a host transcript and insertion
      in the genome. This type of gene duplication, as any other, could be a source of
      new genes and functions. Using whole genome sequence data for 12 Drosophila
      species, we dated the origin of 94 retroposition events that gave rise to
      candidate functional genes in D. melanogaster. RESULTS: Based on this analysis,
      we infer that functional retrogenes have emerged at a fairly constant rate of 0.5
      genes per million years per lineage over the last approximately 63 million years
      of Drosophila evolution. The number of functional retrogenes and the rate at
      which they are recruited in the D. melanogaster lineage are of the same order of
      magnitude as those estimated in the human lineage, despite the higher deletion
      bias in the Drosophila genome. However, unlike primates, the rate of
      retroposition in Drosophila seems to be fairly constant and no burst of
      retroposition can be inferred from our analyses. In addition, our data also
      support an important role for retrogenes as a source of lineage-specific male
      functions, in agreement with previous hypotheses. Finally, we identified three
      cases of functional retrogenes in D. melanogaster that have been independently
      retroposed and recruited in parallel as new genes in other Drosophila lineages.
      CONCLUSION: Together, these results indicate that retroposition is a persistent
      mechanism and a recurrent pathway for the emergence of new genes in Drosophila.

PMID- 17233921
TI  - P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma
      cells via insulin receptor signaling.
AB  - BACKGROUND: Hyperglycemia or hyperinsulinemia contributes to poorer endometrial
      cancer survival. It was shown that P-LAP/IRAP translocates to the plasma membrane
      in response to insulin stimulation. Recently, we demonstrated that P-LAP/IRAP is
      associated with a poor prognosis in endometrial adenocarcinoma patients. The aim
      of this study was to examine whether the malignant potential of endometrial
      cancer enhanced by P-LAP/IRAP is due to increased glucose uptake via the P
      LAP/IRAP-mediated activation of insulin signaling. METHODS: We transfected P
      LAP/IRAP cDNA into A-MEC cells (endometrial adenocarcinoma cell line), and A-MEC
      LAP cells expressed a remarkably high level of GLUT4 proteins. RESULTS: 3H-2
      deoxyglucose uptake which responds to insulin in A-MEC-LAP cells was
      significantly higher than that of A-MEC-pc cells. A-MEC-LAP cells exhibited a
      significant growth-stimulatory effect compared to A-MEC-pc cells. A-MEC-LAP cells
      expressed a remarkably high level of p85PI3K protein compared to A-MEC-pc cells,
      and showed a higher degree of AKT phosphorylation by insulin stimulation.
      CONCLUSION: In summary, P-LAP/IRAP was involved in the increasing malignant
      potential of endometrial cancer mediated by insulin. P-LAP/IRAP was suggested to
      be a potential new target of molecular-targeted therapy for endometrial cancer.

PMID- 17233923
TI  - Perceptions on the importance of gerontological education by teachers and
      students of undergraduate health sciences.
AB  - BACKGROUND: The main challenge of higher education institutions throughout the
      world is to develop professionals capable of understanding and responding to the
      current social priorities of our countries. Given the utmost importance of
      addressing the complex needs of an increasingly elderly population in Mexico, the
      National Autonomous University of Mexico has systematically incorporated modules
      dealing with primary gerontological health care into several of its undergraduate
      programs in health sciences. The objective of this study was to analyze teacher's
      and student's perceptions about the current educational practices on gerontology.
      METHODS: A cross-sectional study was carried out with a sample of 26 teachers and
      122 undergraduate students. Subjects were administered interviews and responded
      survey instrument. RESULTS: A vast proportion of the teachers (42%) reported
      students' attitudes towards their academic training as the most important factor
      affecting learning in the field of gerontology, whereas students reported that
      the main problems of education in gerontology were theoretical (32%) and
      methodological (28%). In addition, 41% of students considered education on ageing
      matters as an essential element for their professional development, as compared
      to 19% of teachers (p < 0.05). CONCLUSION: Our findings suggest that the
      teachers' perceptions about the low importance of education on ageing matters for
      the professional practice of health sciences could be a negative factor for
      gerontology teaching.

PMID- 17233922
TI  - Synthesis and biologic properties of hydrophilic sapphyrins, a new class of tumor
      selective inhibitors of gene expression.
AB  - BACKGROUND: Sapphyrin analogues and related porphyrin-like species have attracted
      attention as anticancer agents due to their selective localization in various
      cancers, including hematologic malignancies, relative to surrounding tissues.
      Sapphyrins are electron affinic compounds that generate high yields of singlet
      oxygen formation. Although initially explored in the context of photodynamic
      therapy, sapphyrins have intrinsic anticancer activity that is independent of
      their photosensitizing properties. However, the mechanisms for their anticancer
      activity have not been fully elucidated. RESULTS: We have prepared a series of
      hydrophilic sapphyrins and evaluated their effect on proliferation, uptake, and
      cell death in adherent human lung (A549) and prostate (PC3) cancer cell lines and
      in an A549 xenograft tumor model. PCI-2050, the sapphyrin derivative with the
      highest in vitro growth inhibitory activity, significantly lowered 5-bromo-2'
      deoxyuridine incorporation in S-phase A549 cells by 60% within eight hours and
      increased levels of reactive oxygen species within four hours. The growth
      inhibition pattern of PCI-2050 in the National Cancer Institute 60 cell line
      screen correlated most closely using the COMPARE algorithm with known
      transcriptional or translational inhibitors. Gene expression analyses conducted
      on A549 plateau phase cultures treated with PCI-2050 uncovered wide-spread
      decreases in mRNA levels, which especially affected short-lived transcripts.
      Intriguingly, PCI-2050 increased the levels of transcripts involved in RNA
      processing and trafficking, transcriptional regulation, and chromatin remodeling.
      We propose that these changes reflect the activation of cellular processes aimed
      at countering the observed wide-spread reductions in transcript levels. In our
      A549 xenograft model, the two lead compounds, PCI-2050 and PCI-2022, showed
      similar tumor distributions despite differences in plasma and kidney level
      profiles. This provides a possible explanation for the better tolerance of PCI
      2022 relative to PCI-2050. CONCLUSION: Hydrophilic sapphyrins were found to
      display promise as novel agents that localize to tumors, generate oxidative
      stress, and inhibit gene expression.

PMID- 17233924
TI  - Papillary meningioma: a rare but distinct variant of malignant meningioma.
AB  - BACKGROUND: Papillary meningiomas are rare meningeal tumors and are associated
      with aggressive clinical behavior as compared with other meningiomas. Because of
      their rare occurrence, they may pose a diagnostic dilemma to the unwary
      pathologist. We report a case of papillary meningioma in a 16-year-old boy. CASE
      PRESENTATION: A 16-year-old boy presented with complaints of headache,
      progressively diminishing vision and more recently generalized seizures. MRI
      revealed a large bifrontal meningioma which showed presence of a predominantly
      papillary pattern with areas of focal necrosis, frequent mitoses and bone
      invasion. He underwent radical excision of the tumor and is free from recurrence
      or metastasis at 15 months follow-up. CONCLUSION: Papillary meningiomas are rare
      but well recognized variants of meningioma. They need to be differentiated from
      other intracranial tumors with a papillary pattern. They are malignant,
      frequently show bone and parenchymatous invasion and have the potential for
      extracranial metastasis. Their timely recognition could prevent local and distant
      metastasis and the mortality or morbidity associated with it.

PMID- 17233925
TI  - Neuromuscular electrical stimulation improves severe hand dysfunction for
      individuals with chronic stroke: a pilot study.
AB  - Restoring hand function is difficult post-stroke. We sought to determine if
      applying neuromuscular electrical stimulation (NMES) was beneficial for reducing
      severe hand impairments. Subjects with chronic stroke (N=8; 3 Fe, 5 M; 58.3 +/-
      6.9 y/o) received 10 sessions of NMES using two different methods applied in a
      counterbalanced order. In one intervention, we applied NMES (active) in a novel
      fashion using multiple stimulators on the forearm flexors and extensors to assist
      subjects with grasping and releasing a tennis ball. In the other intervention,
      the NMES ('passive') stimulated repeated wrist extension and flexion. Motor
      performance was assessed prior to and immediately following the interventions and
      at retention. Upper extremity (UE) Fugl-Myer scores significantly improved (p <
      0.002) immediately following either intervention. Significant improvement was
      also observed in the Modified Ashworth Spasticity Scale (MASS) (p < 0.03),
      immediately following intervention, primarily due to the NMESpassive treatment (p
      < 0.034). Subjects performed grasping tasks significantly faster (p < 0.0433)
      following interventions, with performance speeds on dexterous manipulation
      increasing approximately 10% for NMESactive immediately following intervention,
      compared to only 0.1% improvement following NMESpassive. Generally, improvements
      in motor speed remained 10 days following NMESactive intervention, although
      slightly diminished. In conclusion, severe hand impairment was reduced after a
      short duration of NMES therapy in this pilot data set for individuals with
      chronic stroke. NMES-assisted grasping trended towards greater functional benefit
      than traditional NMES-activation of wrist flexors/extensors.

PMID- 17233926
TI  - Gait changes in response to subthalamic nucleus stimulation in people with
      Parkinson disease: a case series report.
AB  - BACKGROUND AND PURPOSE: For individuals with advanced Parkinson disease (PD),
      stimulation of the subthalamic nucleus (STN) reduces tremor, rigidity, and
      bradykinesia, but the effects of stimulation on gait and mobility are not fully
      understood. The purpose of this paper is to describe the effects of unilateral
      and bilateral STN stimulation on gait following staged stimulator implantations
      in a series of individuals with PD. CASE DESCRIPTIONS: Participants were 6
      individuals with PD who underwent staged stimulator implantation surgeries. The
      effects of stimulation on gait were assessed in the optimally medicated state
      using items from the Unified Parkinson's Disease Rating Scale (UPDRS) related to
      gait and self-reported mobility, time to complete the Timed Up and Go (TUG) test,
      and quantitative gait analysis. Gait was evaluated with stimulation turned off
      and with stimulation turned on after unilateral stimulator implantation and again
      after implantation of the second stimulator. OUTCOMES: Variable effects of
      unilateral and bilateral STN stimulation on gait were observed on UPDRS self
      reported mobility, TUG time, and gait velocity, but changes were not detected
      using the UPDRS gait item. Minimal gait changes, either positive or negative,
      were detected with unilateral stimulation. With bilateral stimulation, gait
      improved for 3 individuals but worsened for the other 3 individuals. DISCUSSION:
      The ability to detect changes in gait after STN stimulation using the UPDRS gait
      item was limited, but variable effects were detected by self-report, TUG time,
      and gait velocity. For half of the individuals studied, bilateral stimulation
      improved these measures, but gait worsened for the remaining individuals. Future
      research is needed to better understand factors that influence the effect of STN
      stimulation on walking, and assessment of gait changes in people with PD should
      include self-report and performance-based measures, such as the TUG test or gait
      velocity.

PMID- 17234010
TI  - Ethical evaluation in health technology assessment reports: an eclectic approach.
AB  - OBJECTIVES: Ethical evaluation has become an important part of health technology
      assessment (HTA), but so far no generally accepted method for doing this exists.
      This article explains the eclectic approach developed at the Finnish HTA office.
      METHODS: Each HTA report is produced in cooperation with the methodological and
      clinical experts from various levels of healthcare organizations. An open
      framework for ethical evaluation when assessing different types of interventions
      is used to identify all possible stakeholders for each particular intervention.
      The ethical consequences for each party are identified during the entire process
      of the HTA project. RESULTS: The results of an ethical evaluation in four
      different HTA projects (two on screening, one on surgical intervention, and one
      in rehabilitation) show that an open framework is useful for opening discussion
      and understanding the scope of each ethical evaluation. Both content and
      methodological experts have found the process to be useful in capturing the broad
      consequences of implementing a new method. CONCLUSIONS: Ethical evaluation is a
      continuous process that considers the prevalent morals, values, and behavioral
      models of the society. An in-depth ethical evaluation helps the decision-makers
      to realize the consequences that implementing a new method has on individual
      citizens, the healthcare system, and society.

PMID- 17234011
TI  - Mapping the integration of social and ethical issues in health technology
      assessment.
AB  - BACKGROUND: Since its inception, the field of health technology assessment (HTA)
      has stressed the need for consideration of ethical and social issues. However,
      few concepts or analytic tools have been developed, and because of the complexity
      of the endeavor and a lack of integration of work already produced, such concepts
      remain difficult to apply in HTA. OBJECTIVES: Through a descriptive "map" of
      concepts, tools, and processes, we summarize the most tangible efforts on the
      part of HTA producers to address social and ethical issues. METHODS: A literature
      review and content analysis of HTA reports in the Centre for Reviews and
      Dissemination database enables a synthesis of the reflections on, initiatives
      around, and gaps in knowledge related to the integration of social and ethical
      issues in HTA. RESULTS: We examine: (i) the aim of integrating ethical and social
      issues in HTA, (ii) the theoretical approaches used, (iii) the methods and
      processes applied, and (iv) the implications for HTA producers. We highlight two
      levels at which social and ethical issues can be considered: throughout the
      production process of HTA reports and as part of the organizational structure of
      HTA agencies. CONCLUSIONS: Given the profound societal changes that occur in
      relation to healthcare technology development, HTA producers have a
      responsibility to inform and enlighten technology-related public and policy
      debates. Fulfilling this role, though, requires that socioethical dimensions of
      technology and HTA are made explicit.

PMID- 17234012
TI  - Differences between research ethics committees.
AB  - OBJECTIVES: To examine differences in the ethical judgments made by Research
      Ethics Committees (RECs) or Institutional Review Boards (IRBs). METHODS: We did a
      review of the literature and included any study that attempted to compare the
      ethical judgments made by different RECs or IRBs when reviewing one or more
      protocol. RESULTS: There were twenty-six articles reporting such discrepancies
      across Europe, within the United Kingdom, Spain, and United States. Of these
      studies, there were only five reports of some RECs approving while others
      rejecting the same protocol. All studies, however, reported differences in the
      clarifications and revisions asked of researchers regarding consent, recruitment,
      risks and benefits, compensation arrangements, and scientific issues.
      CONCLUSIONS: The studies were generally anecdotal reports of researchers trying
      to do research. New rules requiring a single ethical opinion for multi-site
      research at least in European Member States may simply conceal problematic issues
      in REC decision making. In the last analysis, we should expect a certain degree
      of variation and differences if we are to keep a committee system of review,
      although there is a pressing need to investigate the way in which RECs make these
      judgments. In particular, we need to identify the source of any aberrations,
      distortions, or confusions that could arbitrarily affect these judgments.
      Furthermore, local conditions remain important ethical considerations and should
      not be sidelined in pursuit of greater "consistency."

PMID- 17234013
TI  - Primary data collection in health technology assessment.
AB  - This study discusses the value of primary data collection as part of health
      technology assessment (HTA). Primary data collection can help reduce uncertainty
      in HTA and better inform evidence-based decision making. However, methodological
      issues such as choosing appropriate study design and practical concerns such as
      the value of collecting additional information need to be addressed. The authors
      emphasize the conditions required for successful primary data collection in HTA:
      experienced researchers, sufficient funding, and coordination among stakeholders,
      government, and researchers. The authors conclude that, under specific
      conditions, primary data collection is a worthwhile endeavor in the HTA process.

PMID- 17234014
TI  - Patient-based health technology assessment: a vision of the future.
AB  - BACKGROUND: In conjunction with other important movements in contemporary
      medicine, including evidence-based medicine (EBM), health technology assessment
      (HTA) has promoted a culture of critical evaluation. Despite this impact,
      institutional and methodological challenges are associated with HTA. For example,
      only in recent years has HTA attempted an open dialogue with patients; however,
      this is normally done by giving them a "seat" at the HTA decision-making table,
      rather than by more scientific means. OBJECTIVES: The aim of this study was to
      develop a working definition of patient-based HTA, to identify the current
      barriers to adopting a patient-based model, and to formulate a vision of how a
      patient-based HTA could be used to promote patient empowerment and patient
      centered care. RESULTS: In the ideal setting, a patient-based HTA would promote
      patient knowledge by providing access to information and promoting an informed
      dialogue between patients and their healthcare professionals. To implement a
      patient-based HTA, the focus must turn to the patient's issues and incorporate
      each patient's unique perspective and preferences. Processes must change to
      increase patient participation in all levels of HTA and aim to promote empowered
      patients who can make informed decisions. CONCLUSIONS: Present-day HTA is broad
      and has numerous stakeholders, with none so important as the patient. By asking
      patient-oriented questions in HTA and better involving patients throughout the
      entire process, we can easily promote patient empowerment, and as such make
      patients more capable to play a more active role in healthcare decision making.

PMID- 17234015
TI  - Assessing the economic challenges posed by orphan drugs.
AB  - Historically, patients with rare diseases have been underserved by commercial
      drug development. In several jurisdictions, specific legislation has been enacted
      to encourage the development of drugs for rare diseases (orphan drugs), which
      would otherwise not be commercially viable. However, because of the small market,
      these drugs are often very expensive. Under the standard methods of health
      technology assessment (HTA) incorporating economic evaluation, orphan drugs do
      not usually prove to be cost-effective and this, coupled with their high cost,
      means that funding and patient access may be limited. However, these restrictions
      may not be in line with societal preferences. Therefore, this study discusses
      whether the standard methods of HTA are adequate for assisting decisions on
      patient access to and funding of orphan drugs and outlines a research agenda to
      help understand the societal value of orphan drugs and issues surrounding their
      development, funding, and use.

PMID- 17234016
TI  - Economic evaluations of leukemia: a review of the literature.
AB  - OBJECTIVES: Leukemia, together with lymphoma and multiple myeloma, are
      hematological malignancies, malignancies of the blood-forming organs. There are
      four major types of leukemia: acute lymphocytic leukemia (ALL), acute myeloid
      leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia
      (CLL). There is a growing amount of literature of the health economic aspects of
      leukemia. However, no comprehensive review is yet performed on the health
      economic evidence for the disease. Hence, our aim was to review and analyze the
      existing literature on economic evaluations of the different types of leukemia.
      METHODS: A systematic literature search used electronic databases to identify
      published cost analyses and economic evaluations of leukemia treatments. After
      reviewing all identified studies, sixty studies were considered relevant for the
      purpose of the review. RESULTS: The identified studies were published after 1990,
      with a few exceptions. Many of the identified economic evaluations in leukemia,
      particularly for ALL and AML, may be defined as cost-minimization analyses, where
      only the costs of different treatment strategies are compared. In CML, a new
      treatment, imatinib, was introduced in 2001 and several cost-effectiveness
      analyses have since then been conducted comparing imatinib with previous first
      line treatments. CONCLUSIONS: This review indicates that there is a shortage of
      cost-effectiveness information in leukemia. The introduction of new therapies
      will stress the need for new economic evaluations in this group of diseases. More
      information about the total costs, that is, including indirect costs, and quality
      of life effects would be valuable in future evaluations in leukemia.

PMID- 17234017
TI  - Effectiveness and safety of endoscopic thoracic sympathectomy for excessive
      sweating and facial blushing: a systematic review.
AB  - OBJECTIVES: Despite controversies, endoscopic thoracic sympathectomy (ETS) has
      been used as a treatment for excessive sweating of hands and face and for facial
      blushing. This study aims to evaluate the effectiveness of ETS for the current
      indications in a systematic review. METHODS: Controlled clinical trials and
      cohort studies with more than 100 patients were included. Abstracts were searched
      from MEDLINE and CCTR from 1966 to June 2004. Two reviewers extracted the data
      and assessed study quality. Data on effectiveness and safety were synthesized
      qualitatively. RESULTS: We did not find any controlled clinical trials. Fifteen
      prospective studies were included. The internal and external quality of these
      studies were poor overall. Follow-up was commonly less than 2 years, during which
      time excessive sweating and facial blushing seemed to decrease among most
      patients. Immediate complications related to thoracoscopy occurred in up to 10
      percent of patients. Compensatory sweating below breast level was reported in up
      to 90 percent of the patients. Other common side effects included dryness of face
      and hands, gustatory sweating, and neuralgic pain. Several other less common side
      effects were reported. CONCLUSIONS: The evidence of the effectiveness of ETS is
      weak due to a lack of randomized trials. The intervention leads to severe
      immediate complications in some of the patients, and to persistent side-effects
      for many of the patients.

PMID- 17234018
TI  - Clinical effectiveness and cost-effectiveness of implantable cardioverter
      defibrillators for arrhythmias: a systematic review and economic evaluation.
AB  - OBJECTIVES: The clinical effectiveness and cost-effectiveness of implantable
      cardioverter defibrillators (ICD) for arrhythmias was assessed. METHODS: A
      systematic review of the literature of systematic reviews and randomized
      controlled trials that reported mortality outcomes associated with implantable
      cardioverter defibrillators compared with antiarrhythmic drug therapy in people
      at risk of sudden cardiac death due to arrhythmias was undertaken. Economic
      evaluations were also sought. Inclusion criteria, data extraction, and quality
      assessment were undertaken by standard methodology. A decision analytic model was
      constructed using best available evidence to determine cost-effectiveness in a UK
      setting. RESULTS: Eight randomized controlled trials, two systematic reviews, and
      a meta-analysis met the inclusion criteria and were of variable quality. Evidence
      suggests that ICDs reduce mortality in both secondary and primary prevention,
      although the magnitude of benefit depends on baseline risk for sudden cardiac
      death. Incremental cost per quality-adjusted life year ranged from 52,000 UK
      pounds ($98,000) to over 200,000 UK pounds ($379,000), depending on mortality
      risk and assumptions made. CONCLUSIONS: Evidence suggests that ICDs reduce total
      mortality but may be cost-effective only in some subgroups of patients at high
      risk of ventricular arrhythmias. Further research is needed on risk
      stratification of patients in whom ICDs are most likely to be clinically and cost
      effective.

PMID- 17234019
TI  - Primary prevention of cardiovascular disease: cost-effectiveness comparison.
AB  - OBJECTIVES: The aim of this study was to evaluate the cost-effectiveness of four
      risk-lowering interventions (smoking cessation, antihypertensives, aspirin, and
      statins) in primary prevention of cardiovascular disease. METHODS: Using data
      from the Framingham Heart Study and the Framingham Offspring study, we built life
      tables to model the benefits of the selected interventions. Participants were
      classified by age and level of risk of coronary heart disease. The effects of
      risk reduction are obtained as numbers of death averted and life-years saved
      within a 10-year period. Estimates of risk reduction by the interventions were
      obtained from meta-analyses and costs from Dutch sources. RESULTS: The most cost
      effective is smoking cessation therapy, representing savings in all situations.
      Aspirin is the second most cost-effective (euro 2,263 to euro 16,949 per year of
      life saved) followed by antihypertensives. Statins are the least cost-effective
      (euro 73,971 to euro 190,276 per year of life saved). CONCLUSIONS: A cost
      effective strategy should offer smoking cessation for smokers and aspirin for
      moderate and high levels of risk among men 45 years of age and older. Statin
      therapy is the most expensive option in primary prevention at levels of 10-year
      coronary heart disease risk below 30 percent and should not constitute the first
      choice of treatment in these populations.

PMID- 17234020
TI  - Cost-effectiveness of an education and activation program for patients with acute
      and subacute shoulder complaints compared to usual care.
AB  - OBJECTIVES: Shoulder complaints (SCs) constitute the second largest group of
      musculoskeletal disorders after low back pain. The economic burden in terms of
      costs of healthcare use and costs due to work absenteeism underlines the need for
      a cost-effectiveness analysis of the interventions involved. The education and
      activation program (EAP) is a newly developed early intervention to prevent the
      development of chronic SCs. A cost-effectiveness analysis should provide more
      information on the effect of an EAP on total costs related to SCs. METHODS: We
      conducted a cost-effectiveness analysis alongside a randomized clinical trial
      comparing the effectiveness of the EAP in addition to usual care (EAP group) with
      that of usual care alone (UC group) in terms of preventing chronicity in patients
      with acute SCs. The aim of the cost-effectiveness analysis was to compare the
      observed difference in costs with the clinical effectiveness (i.e., patient
      perceived recovery after 26 weeks), using bootstraps. RESULTS: The comparison of
      total costs between treatment groups showed no significant (p = .077) difference
      after 26 weeks. The majority (82 percent) of the cost-effect pairs after
      bootstrap analysis were located in the northeast quadrant, suggesting more effect
      but at higher costs. CONCLUSIONS: In view of the clinical relevance of the
      clinical outcomes and the considerable costs needed to achieve this, it can be
      concluded that the EAP is currently not cost-effective.

PMID- 17234021
TI  - Cost-effectiveness of surveillance programs for families at high and moderate
      risk of hereditary non-polyposis colorectal cancer.
AB  - OBJECTIVES: Surveillance programs are recommended to both families at high risk
      (Amsterdam-positive families with known- and unknown mutation) and moderate risk
      (families not fulfilling all Amsterdam criteria) of colorectal cancer (CRC). Cost
      effectiveness has so far only been estimated for the group at high risk. The aim
      of the present study is to determine cost-effectiveness of surveillance programs
      where families at both high and moderate risk of HNPCC participate. METHODS: A
      decision analytic model (Markov model) is developed to assess surveillance
      programs where families at high and moderate risk of HNPCC are offered
      surveillance from age 25 and age 45, respectively. The model includes costs for
      all families referred to genetic counseling, including genetic risk assessment,
      mutation analysis, and surveillance in relevant families with or without known
      mutation, plus the costs related to any surgical treatment. The risk of
      metachronous CRC is also modeled. RESULTS: Incremental costs per life year gained
      are estimated to be euro 980 when families at both high and moderate risk of
      HNPCC undergo surveillance (euro 508 for high risk and euro 1600 for moderate
      risk) and euro 1947 when the moderate risk group is evaluated genetically but not
      offered surveillance. Sensitivity analysis showed these findings to be robust,
      although cost-effectiveness can be improved in cases of more conservative
      referrals to genetic counseling. CONCLUSIONS: The result for high risk families
      confirms the findings in similar studies. Somewhat surprisingly, cost
      effectiveness improves when surveillance of the moderate risk groups are included
      in the decision model.

PMID- 17234022
TI  - Exploration of the difference in results of economic submissions to the National
      Institute of Clinical Excellence by manufacturers and assessment groups.
AB  - OBJECTIVES: A recent study showed that estimates of cost-effectiveness submitted
      to National Institute for Health and Clinical Excellence (NICE) by manufacturers
      had significantly lower incremental cost-effectiveness ratios (ICERs) than those
      submitted by university-based Assessment Groups. This study extends that
      analysis. METHODS: Data were abstracted from relevant NICE documentation for
      thirty-two of eighty-two possible appraisals. RESULTS: The results from the
      analysis showed that sources of the difference in ICERs appear to be the
      effectiveness estimates relating to the comparator technology and the cost
      estimates relating to the technology under evaluation. That is, manufacturers
      estimated lower average benefits for the comparator technology and lower costs
      relating to the technology under evaluation compared with estimates submitted by
      the Assessment Groups. CONCLUSIONS: These findings may be particularly important,
      given the introduction of the "Single Technology Appraisal." Considerable
      difficulties were encountered when undertaking this study, highlighting, above
      all else, the complexity of explaining why results from economic evaluations
      purporting to answer the same question diverge.

PMID- 17234023
TI  - Association of study type, sample size, and follow-up length with type of
      recommendation produced by the National Institute for Health and Clinical
      Excellence Interventional Procedures Programme.
AB  - OBJECTIVES: The association between type and amount of clinical evidence and type
      of National Institute for Health and Clinical Excellence recommendations for
      interventional procedures was examined. METHODS: The evidence about 736 studies
      (including 183,729 patients) relating to 130 different interventional procedures
      and about relevant recommendations was analyzed. Associations were examined
      between type of recommendation ("normal arrangements" or "cautionary guidance")
      and evidence type, total number of treated patients, and mean follow-up length.
      Evidence type was categorized as (a) randomized, (b) nonrandomized controlled,
      and (c) case series/reports. The main outcome measures were frequency of evidence
      type, total number of patients treated, and mean follow-up length, by type of
      recommendation. RESULTS: "Normal arrangements" recommendations were made for 70
      (54 percent) procedures and "cautionary guidance" was issued for 60 (46 percent)
      procedures. Procedures supported by at least one randomized study (34 percent, n
      = 44) were more likely to receive a "normal arrangements" recommendation
      (relative risk 1.38, p = .063). Overall, there were 85 (12 percent), 135 (18
      percent), and 516 (70 percent) studies in categories a-c, respectively. The
      number of treated patients was significantly larger among procedures with "normal
      arrangements" (median, 605; range, 26-6,842) than among those with "cautionary
      guidance" (median, 240; range, 1-3,261; p < .001) recommendation. Mean follow-up
      length was longer in studies relating to procedures with "normal arrangements"
      recommendation (median, 16.7; range, 0-84 months) compared with those with
      "cautionary guidance" (median, 14.6; range, 0-67 months; p = .160). CONCLUSIONS:
      Procedures supported by randomized studies, and with larger numbers of patients
      and longer follow-up length, were more likely to receive positive guidance.
      Future research and development on interventional procedures should aim to
      produce better and more relevant evidence to optimize the possibility of such
      procedures being accepted by policy makers.

PMID- 17234024
TI  - An experimental study of the influence of individual participant characteristics
      on formal consensus development.
AB  - OBJECTIVES: The aim of this study was to examine the influence of participants'
      characteristics on the results produced by formal consensus methods. METHODS: The
      approach was an experimental study of 346 participants in 20 groups rating the
      appropriateness of four mental health interventions for the treatment of chronic
      fatigue syndrome, irritable bowel syndrome, and chronic back pain. There were
      four factors in the design: systematic literature review provided or not,
      decisions made under realistic or "ideal" resource assumptions, clinically mixed
      (general practitioners and mental health professionals) or homogenous group
      (general practitioners only), convened or mail-only group. A group's rating was
      defined as the median of participants' ratings. The influence of participants'
      characteristics (age, sex, and specialty) was examined using multilevel models.
      RESULTS: The largest differences were between the GPs and mental health
      professionals, both in their initial ratings of the different interventions, and
      in how much they altered their ratings between rounds. There were smaller but
      statistically significant (p<.05) differences between specialty and age groups in
      initial ratings for the treatment (by whatever means) of different conditions,
      and for certain conditions women increased their ratings more than men. Women
      rated intervention more favorably when assuming "ideal" rather than realistic
      levels of resources, but men did not. CONCLUSIONS: Our findings support the
      practice of treating professional specialty as an important determinant of the
      results in consensus panels.

PMID- 17234025
TI  - Telemedicine in pediatric and perinatal cardiology: economic evaluation of a
      service in English hospitals.
AB  - OBJECTIVES: Pediatric cardiology has an expanding role in fetal and pediatric
      screening. The aims of this study were to observe how district hospitals use a
      pediatric telecardiology service, and to compare the costs and outcomes of
      patients referred to specialists by means of this service or conventionally.
      METHODS: A telemedicine service was set up between a pediatric cardiac center in
      London and four district hospitals for referrals of second trimester women,
      newborn babies, and older children. Clinicians in each hospital decided on the
      role for their service. Clinical events were audited prospectively and costed,
      and patient surveys were conducted. RESULTS: The hospitals differed in their
      selection of patient groups for the service. In all, 117 telemedicine patients
      were compared with 387 patients seen in London or in outreach clinics. Patients
      selected for telemedicine were generally healthier. For all patients, the mean
      cost for the initial consultation was 411 UK pounds for tele-referrals and 277 UK
      pounds for conventional referrals, a nonsignificant difference. Teleconsultations
      for women and children were significantly more expensive because of technology
      costs, whereas for babies, ambulance transfers were much more costly. After 6
      months follow-up, the difference between referral methods for all patients was
      nonsignificant (telemedicine, 3,350 UK pounds; conventional referrals, 2,172 UK
      pounds), and nonsignificant within the patient groups. CONCLUSIONS: Telemedicine
      was perceived by cardiologists, district clinicians, and families as reliable and
      efficient. The equivocal 6-month cost results indicate that investment in the
      technology is warranted to enhance pediatric and perinatal cardiology services.

PMID- 17234026
TI  - Dialysis care, cardiovascular disease, and costs in end-stage renal disease in
      Brazil.
AB  - OBJECTIVES: This study evaluates the cost of dialysis care in Brazil, including
      costs of ambulatory care and hospital admissions due to all causes and
      cardiovascular events. METHODS: Data were analyzed for 200 patients with end
      stage renal disease (ESRD) on chronic hemodialysis in Brazil between 2001 and
      2004. Main end points were all-cause mortality, all-cause hospital admissions,
      and cardiovascular events. Direct costs of dialysis treatment and complications
      were computed from the perspective of two payers, the Ministry of Health (MoH)
      and private health insurance (PHI). RESULTS: Mean number of days of
      hospitalization was 12 per patient-year. There were 105 cardiovascular events;
      the most frequent events were coronary disease (n = 59, 56 percent) and
      congestive heart failure (n = 26, 25 percent). The rate of cardiovascular events
      was 193 per 1,000 patient-years. There were 43 deaths, and the death rate was 79
      per 1,000 patient-years. Median cost per hospital admission was US$ 675 and US$
      932 from the perspective of the MoH and PHI. For admissions due to cardiovascular
      causes, the corresponding costs were US$ 1,639 and US$ 4,499, respectively. Mean
      global cost per patient-year for chronic hemodialysis therapy was US$ 7,980 and
      US$ 13,428 from the perspective of the MoH and PHI, respectively. CONCLUSIONS:
      Patients on chronic hemodialysis care incur significant healthcare resources due
      to the costs of dialysis and complications, notably cardiovascular disease. New
      disease management programs aimed at reducing cardiovascular morbidity and
      efficient use of resources are critical to ensuring the sustainability of
      treatments for ESRD in Brazil.

PMID- 17234027
TI  - Benefits of and barriers to involving users in medical device technology
      development and evaluation.
AB  - OBJECTIVES: This study investigated the benefits of and barriers to user
      involvement in medical device technology development and evaluation. METHODS: A
      structured review of published literature in peer-reviewed journals was
      conducted. RESULTS: This literature review revealed that the main benefits of
      user involvement were an increased access to user needs, experiences, and ideas;
      improvements in medical device designs and user interfaces; and an increase in
      the functionality, usability, and quality of the devices. On the other hand,
      resource issues, particularly those of time and money were found the key
      impediments to involving users in the development and evaluation of medical
      device technologies. This study also has categorized both the benefits of and
      barriers to user involvement. CONCLUSIONS: The involvement of users in medical
      device technology development and evaluation requires resources, which are
      limited; however, this involvement is essential from both users and manufacturers
      perspectives.

PMID- 17234028
TI  - Cost-effectiveness analysis of prenatal diagnosis intervention for Down's
      syndrome in China.
AB  - OBJECTIVES: The cost-effectiveness of prenatal diagnosis intervention for Down's
      syndrome (DS) in China was assessed and evidence-based information for policy
      makers and providers is presented. METHODS: Based on field surveys in four
      selected cities in China and a literature review, the economic evaluation of
      prenatal diagnosis for DS from a societal perspective is conducted by cost
      effectiveness analysis. RESULTS: In current clinical practice, for a cohort of
      10,000 pregnant women, the strategy that delivers karyotyping by chorionic villus
      sampling (CVS) or amniocentesis (AC) only to those pregnant women 35 years of age
      and older (maternal age screening strategy) can detect .67 DS births. The
      strategy that offers the diagnostic test after maternal serum screening with
      alpha-fetoprotein and human chorionic gonadotrophin (maternal serum screening
      strategy) can detect 1.41 DS births. The cost per prevented DS birth by the
      maternal age screening strategy and maternal serum screening strategy is US$
      13,091 and US$ 56,048, respectively. Sensitivity analysis shows that the maternal
      serum screening strategy can be cost-effective if uptake rate of CVS or AC for
      patients with positive serum tests increase while the cost of serum screening
      decreases. CONCLUSIONS: Although, in general, serum screening has been found to
      be more cost-effective than maternal age screening, this appears not to be the
      case in China. The reasons appear to be low uptake rate of the maternal serum
      strategy, low uptake rate of CVS or AC, and the high price of serum screening.
      Our findings are that health system factors concerning technology utilization are
      important determinants of the technology's efficiency.

PMID- 17234029
TI  - Frederick Mosteller (1916-2006): mentoring, a memoir.

PMID- 17234031
TI  - Atomic force microscopy dissects the hierarchy of genome architectures in
      eukaryote, prokaryote, and chloroplast.
AB  - Because of its applicability to biological specimens (nonconductors), a single
      molecule-imaging technique, atomic force microscopy (AFM), has been particularly
      powerful for visualizing and analyzing complex biological processes. Comparative
      analyses based on AFM observation revealed that the bacterial nucleoids and human
      chromatin were constituted by a detergent/salt-resistant 30-40-nm fiber that
      turned into thicker fibers with beads of 70-80 nm diameter. AFM observations of
      the 14-kbp plasmid and 110-kbp F plasmid purified from Escherichia coli
      demonstrated that the 70-80-nm fiber did not contain a eukaryotic nucleosome-like
      "beads-on-a-string" structure. Chloroplast nucleoid (that lacks bacterial-type
      nucleoid proteins and eukaryotic histones) also exhibited the 70-80-nm structural
      units. Interestingly, naked DNA appeared when the nucleoids from E. coli and
      chloroplast were treated with RNase, whereas only 30-nm chromatin fiber was
      released from the human nucleus with the same treatment. These observations
      suggest that the 30-40-nm nucleoid fiber is formed with a help of nucleoid
      proteins and RNA in E. coli and chroloplast, and that the eukaryotic 30-nm
      chromatin fiber is formed without RNA. On the other hand, the 70-80-nm beaded
      structures in both E. coli and human are dependent on RNA.

PMID- 17234032
TI  - An antibody-sensitized microfabricated cantilever for the growth detection of
      Aspergillus niger spores.
AB  - We demonstrate a new sensitive biosensor for detection of vital fungal spores of
      Aspergillus niger. The biosensor is based on silicon microfabricated cantilever
      arrays operated in dynamic mode. The change in resonance frequency of the sensor
      is a function of mass binding to the cantilever surface. For specific A. niger
      spore immobilization on the cantilever, each cantilever was individually coated
      with anti-Aspergillus niger polyclonal antibodies. We demonstrate the detection
      of single A. niger spores and their subsequent growth on the functionalized
      cantilever surface by online measurements of resonance frequency shifts. The new
      biosensor operating in humid air allows quantitative and qualitative detection of
      A. niger spores as well as detection of vital, functional spores in situ within
      approximately 4 h. The detection limit of the sensor is 103 CFU mL-1. Mass
      sensitivity of the cantilever sensor is approximately 53 pg Hz-1.

PMID- 17234033
TI  - Flow cytometric viability assessment and transmission electron microscopic
      morphological study of bacteria in glycerol.
AB  - Human cadaveric skin allografts are used in the treatment of burns and can be
      preserved in glycerol at high concentrations. Previously, glycerol has been
      attributed some antimicrobial effect. In an experimental set-up, we aimed at
      investigating this effect of prolonged incubation of bacteria in 85% glycerol.
      Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, and
      Bacillus subtilis were incubated in 85% glycerol. The influence of duration of
      incubation and temperature on ultrastructure and viability were investigated.
      Unstressed cultures served as controls. Survival was studied after 24-36 h and 10
      days incubation in 85% glycerol at 4 degrees C and 36 degrees C with transmission
      electron microscopy (TEM) and flow cytometry using viability stains indicating
      membrane damage (SYTO9, propidium iodide) or esterase activity
      (carboxyfluorescein diacetate). TEM clearly demonstrated variability in
      morphological changes of bacteria suggesting different mechanisms of damage.
      Viability stains supported these findings with faster declining viable cell
      populations in 85% glycerol at 36 degrees C compared with 4 degrees C. Both
      methods demonstrated that Gram-negative species were more susceptible than Gram
      positive species. In conclusion, 85% glycerol may have some additional
      antimicrobial effect. Temperature is an important factor herein and Gram
      negatives are most susceptible. The latter finding probably reflects the
      difference in cell wall composition between Gram-positive and Gram-negative
      bacteria.

PMID- 17234034
TI  - Biochemical, molecular genetic, and structural analyses of the staphylococcal
      nucleoid.
AB  - The nucleoid structure of an important human pathogen, Staphylococcus aureus, was
      dissected by atomic force microscopy (AFM). The nucleoids dispersed on a cover
      glass consisted of fibrous units with two different widths of 40 and 80 nm, a
      feature shared with those of Escherichia coli. On the other hand, cells exposed
      to an oxidative stress exhibited clogged nucleoids. A knock-out of mrgA (metallo
      regulated genes A) encoding a staphylococcal homolog of the nucleoid compaction
      factor (E. coli Dps) eliminated the compaction response to the oxidative stress
      and reduced the susceptibilities to H2O2 and UV irradiation. We also observed
      that the negative supercoiling of plasmids is increased by the oxidative stress.
      A possible interrelation between the helical density and the nucleoid compaction
      is discussed in relation to the oxidative stress response.

PMID- 17234035
TI  - Detection of filamentous bulking problems: developing an image analysis system
      for sludge composition monitoring.
AB  - This article describes a fully automatic image analysis procedure for fast and
      reliable characterization of the activated sludge composition, that is, the floc
      and filament features. The algorithms developed for each of the analysis steps,
      that is, segmentation, object recognition, and characterization, are described in
      detail. Although the application range of the recognition method is a priori
      expanded by introducing a number of control parameters, the procedure proves to
      be intrinsically robust as it produces satisfactory results for a fixed set of
      parameter values for a wide variety of image types.

PMID- 17234036
TI  - Bacterially induced mineralization of calcium carbonate: the role of
      exopolysaccharides and capsular polysaccharides.
AB  - Bacterially induced carbonate mineralization has been proposed as a new method
      for the restoration of limestones in historic buildings and monuments. We
      describe here the formation of calcite crystals by extracellular polymeric
      substances isolated from Bacillus firmus and Bacillus sphaericus. We isolated
      bacterial outer structures (glycocalix and parietal polymers), such as
      exopolysaccharides (EPS) and capsular polysaccharides (CPS) and checked for their
      influence on calcite precipitation. CPS and EPS extracted from both B. firmus and
      B. sphaericus were able to mediate CaCO3 precipitation in vitro. X-ray
      microanalysis showed that in all cases the formed crystals were calcite. Scanning
      electron microscopy showed that the shape of the crystals depended on the
      fractions utilized. These results suggest the possibility that biochemical
      composition of CPS or EPS influences the resulting morphology of CaCO3. There
      were no precipitates in the blank samples. CPS and EPS comprised of proteins and
      glycoproteins. Positive alcian blue staining also reveals acidic polysaccharides
      in CPS and EPS fractions. Proteins with molecular masses of 25-40 kDa and 70 kDa
      in the CPS fraction were highly expressed in the presence of calcium oxalate.
      This high level of synthesis could be related to the binding of calcium ions and
      carbonate deposition.

PMID- 17234037
TI  - Study of the VirE2-ssT-DNA complex formation by scanning probe microscopy and gel
      electrophoresis- T-complex visualization.
AB  - The recombinant virulence protein VirE2, capable of forming a complex with single
      stranded T-DNA during transfer into plant cells, was isolated, purified, and used
      for interactions with ssT-DNA. The in vitro interaction of VirE2 and ss-binding
      protein from Escherichia coli with single-stranded DNA (phage lambda) was
      determined by agarose gel electrophoresis by the formation of high-molecular
      weight complexes after preliminary coincubation of purified protein preparations
      with ssDNA. We show that VirE2 binds to single-stranded DNA and protects it
      against nuclease S1 degradation much better than does E. coli SSB protein. We for
      first time observed the VirE2-ssT-DNA complex by using atomic force microscopy.
      The complex observed by atomic force microscopy after ssT-DNA and VirE2 protein
      mixing has a length of about 800 nm and a 5-8 nm width in sites with attached
      VirE2 protein.

PMID- 17234038
TI  - Atomic force microscopy of mechanically trapped bacterial cells.
AB  - This article presents a study on the influence of the protocol used for
      immobilization of bacterial cells onto surfaces by mechanically trapping them
      into a filter. In this sense, the surface and structure of trapped cells are
      analyzed. Bacteria can be present solely or with extracellular polymeric
      substances (EPS). To test the behavior of the EPS layer duing the filtering
      process, different strains of a well-known EPS-producer bacteria (Staphylococcus
      epidermidis), which produce an extracellular matrix clearly visible in AFM
      images, have been used. Results show that this immobilization method can cause
      severe structural and mechanical deformation to the cell membrane. This altered
      mechanical state may possibly influence the parameters derived from AFM force
      curves (which are micro/nano-mechanical tests). Also, our results suggest that
      the EPS layer might move during the filtering process and could accumulate at the
      upper part of the cell, thus favoring distorted data of adhesion/pull-off forces
      as measured by an AFM tip, especially in the case of submicron-sized microbial
      cells such as bacteria.

PMID- 17234039
TI  - Persistent vegetative state and dementia in the elderly.
AB  - BACKGROUND: Very few studies have approached the issue of persistent vegetative
      state (PVS) within the elderly population. This study aims to assess the
      prevalence, determinants and prognosis of elderly patients with PVS admitted to a
      long-term geriatric facility. METHODS: We conducted a cohort study in the setting
      of a Skilled Geriatric Nursing Department. All patients admitted during a 17
      month period (N = 88) were included and tested for a diagnosis of PVS according
      to the Disability Rating Scale (DRS). RESULTS: A clinical diagnosis of PVS was
      given to 15% of patients upon admission, whereas the DRS diagnosed 30.5% of
      patients as having PVS. During the study period, 12 out of 31 patients with PVS
      died, with a median survival of 127 days (range: 1-517 days). CONCLUSION: Our
      study suggests that PVS is an advanced stage in the natural history of dementia
      in the elderly. The low proportion of patients with PVS recognized as having this
      disorder upon admission suggests a low awareness among hospital personnel.
      Further studies of the prevalence and determinants of PVS in the severely
      disabled elderly population are warranted.

PMID- 17234040
TI  - An assessment of the attitudes of potential caregivers toward the abuse of
      elderly persons with and without dementia.
AB  - BACKGROUND: Dementia in the elderly is associated with a greater risk of being
      subjected to abuse. More than half of those in Japan who abuse elderly relatives
      with dementia do not realize that their behavior corresponds to abuse. OBJECTIVE:
      This study sought to examine the effect of the presence of dementia in the
      elderly on attitudes toward abuse. METHODS: The subjects of this study were 135
      people aged between 18 and 86 who were not taking care of elderly relatives at
      the time of the survey. The subjects were asked to rate how abusive they thought
      each of 12 behaviors listed in a questionnaire was in regard to three categories
      of elderly: (1) elderly with dementia who require care (DC); (2) elderly without
      dementia who require care (NC); and (3) elderly without dementia who do not
      require care (NN). RESULTS: The results of ANOVAs showed that the attitude of the
      subjects was associated with experience of caregiving, category of elderly, and
      type of abuse. The results of Bonferroni's tests indicated that the behaviors,
      especially those behaviors that included physical, psychological, and economic
      abuse, toward the DC category were not considered to be as abusive as those
      toward either the NC category or NN category. CONCLUSIONS: This study suggests
      that people might rate abusive behavior as being less abusive when the person
      being cared for has dementia.

PMID- 17234041
TI  - A controlled trial of a predominantly psychosocial approach to BPSD: treating
      causality.
AB  - BACKGROUND: The adverse effects of behavioral and psychological symptoms of
      dementia (BPSD) are well described but treatment remains problematical, including
      overuse of psychotropic medication. This study aims to compare the outcome of two
      approaches to BPSD, one focusing on causality and using predominantly
      psychosocial interventions, the other relying predominantly on psychotropic
      medication. METHODS: Thirty-three residential care clients manifesting BPSD who
      had been referred to a community psychogeriatric service (intervention group)
      were assessed and treated, with the focus placed on the causes of the behavior
      and why it was perceived as a problem by nursing staff. Cases were managed
      primarily by psychosocial means with psychopharmacology as an adjunct. A control
      group was made up of 22 referrals to an adjacent service, which used primarily
      psychopharmacology with psychosocial methods as an occasional adjunct. RESULTS:
      Measures of behavior and staff response showed significant improvement in both
      groups at two- and five-months' follow-up. Antipsychotic use in the intervention
      group decreased over time while in the control group it increased. Service
      measures showed both groups required approximately the same number of clinical
      visits but the intervention group experienced fewer medication changes, fewer
      drug side effects, and all but one case could be treated in situ. Five control
      group participants spent extended periods as inpatients in a psychogeriatric
      unit. Minor sampling differences did not affect the results, and neither they nor
      the nature of the behavior explained the difference in clinical approach.
      CONCLUSION: The causality-focused approach appears to be as effective as the more
      common predominantly pharmacological approach, and appears to involve lower human
      and financial costs.

PMID- 17234042
TI  - Patterns of relatedness in the Kudoidae with descriptions of Kudoa chaetodoni n.
      sp. and K. lethrini n. sp. (Myxosporea: Multivalvulida).
AB  - Two morphologically novel Kudoa species are characterized from brain tissue of
      fish, Kudoa chaetodoni n. sp. from Chaetodon unimaculatus (Chaetodontidae) and
      Kudoa lethrini n. sp. from Gymnocranius audleyi and Lethrinus harak
      (Lethrinidae). Additionally we characterized a 5-spore valve (SV) Kudoa species
      from the brain of Sillago ciliata (Sillaginidae). Intriguingly, its 18S rDNA
      sequence was identical to that of the 7 SV Kudoa yasunagai extracted from the
      brain of a paralichthyid halibut in Japan. These 2 species may either prove to be
      con-specific, even though morphology and distribution differ, or demonstrate the
      limit of specific resolution in the small subunit rDNA gene region. Small subunit
      rDNA sequences from these new species were used in molecular phylogenetic
      analyses of kudoids to examine congruence of phylogeny with tissue tropism,
      geographical distribution, and host specificity. There was significant
      correlation between tissue tropism in the form of well-supported brain and heart
      infecting clades. Host specificity and geographical distribution showed some
      correlations with genotype.

PMID- 17234043
TI  - Are there general laws in parasite ecology?
AB  - As a scientific discipline matures, its theoretical underpinnings tend to
      consolidate around a few general laws that explain a wide range of phenomena, and
      from which can be derived further testable predictions. It is one of the goals of
      science to uncover the general principles that produce recurring patterns in
      nature. Although this has happened in many areas of physics and chemistry,
      ecology is yet to take this important step. Ecological systems are intrinsically
      complex, but this does not necessarily mean that everything about them is
      unpredictable or chaotic. Ecologists, whose grand aim is to understand the
      interactions that govern the distribution, abundance and diversity of living
      organisms at different scales, have uncovered several regular patterns, i.e.
      widely observable statistical tendencies, in the abundance or diversity of
      organisms in natural ecosystems. Some of these patterns, however, are contingent,
      i.e. they are only true under particular circumstances; nevertheless, the broad
      generality of many patterns hints at the existence of universal principles. What
      about parasite ecology: is it also characterized by recurring patterns and
      general principles? Evidence for repeatable empirical patterns in parasite
      ecology is reviewed here, in search of patterns that are consistently detectable
      across taxa or geographical areas. The coverage ranges from the population level
      all the way to large-scale patterns of parasite diversity and abundance (or
      biomass) and patterns in the structure of host-parasite interaction networks.
      Although general laws seem to apply to these extreme scales of studies, most
      patterns observed at the intermediate scale, i.e. the parasite community level,
      appear highly contingent and far from universal. The general laws uncovered to
      date are proving valuable, as they offer glimpses of the underlying processes
      shaping parasite ecology and diversity.

PMID- 17234044
TI  - Immobilization antibodies of tiger puffer Takifugu rubripes induced by i.p.
      injection against monogenean Heterobothrium okamotoi oncomiracidia do not prevent
      the infection.
AB  - We examined whether infection by the monogenean Heterobothrium okamotoi induces
      production of specific antibodies against oncomiracidia and their cilia, larvae
      on the gills, and adults on the branchial cavity wall of tiger puffer Takifugu
      rubripes. We also investigated whether specific antibody production participates
      in acquired protection against H. okamotoi. Sera from persistently infected fish
      immobilized H. okamotoi oncomiracidia 89 days after exposure and antibody levels
      (measured by enzyme-linked immunosorbent assays) in the sera against
      oncomiracidia and their cilia increased compared with sera from control (naive)
      fish. Antibody levels in these sera against the larvae and adult stages did not
      increase. The number of H. okamotoi on persistently infected fish was
      significantly lower than for control fish (P<0.05) when persistently infected
      fish and control fish were exposed to oncomiracidia in the same tank. Thus tiger
      puffer produced specific antibodies against oncomiracidia and their cilia, and
      acquired partial protection against H. okamotoi. Intraperitoneal injection of
      proteins of sonicated oncomiracidia or their cilia with an adjuvant also produced
      oncomiracidium agglutination antibodies in sera from tiger puffer; the antibody
      levels in these sera against oncomiracidia and their cilia increased compared
      with sera from control fish (injection of BSA with an adjuvant) at 14, 44, and 75
      days after the booster immunization. However, in a parasite challenge at 54-58
      days after the booster immunization, the infection levels of fish immunized with
      parasites of sonicated oncomiracidia or their cilia were the same as the control
      fish. Western blot showed that sera from persistently infected fish and fish
      immunized with sonicated oncomiracidia or their cilia recognized similar
      antigenic bands, suggesting that tiger puffer tends to react against these
      antigens compared with other antigens. These results indicated that specific
      antibodies against these cilia and oncomiracidia induced by i.p. injection do not
      prevent H. okamotoi infection.

PMID- 17234045
TI  - Numerical response of a helminth community in the course of a multi-annual
      abundance cycle of the water vole (Arvicola terrestris).
AB  - The impact of parasitism on population dynamics is determined in part by the
      numerical responses of parasites during population fluctuations of their hosts.
      Vole populations fluctuate in multi-annual cycles allowing such responses to be
      studied over successive phases of population growth, abundance and decline. We
      investigate how a helminth community (5 nematode and 7 cestode species) evolved
      over a full 6-year Water Vole (Arvicola terrestris) population cycle. Brillouin
      and individual parasite species richness (IPSR) indices were used to measure the
      numerical response of the parasite community. We report a correlation between
      levels of parasite intensity and vole population cycle phases. Both indices were
      consistently higher during pre-decline and decline phases for male and female
      voles alike. The numerical response of the parasite community suggests that
      populations may be regulated by parasitism and that studies of this mechanism
      should allow both for the cyclic or non-cyclic character of the host populations
      and for the response of the broadest possible set of the local parasite
      community.

PMID- 17234046
TI  - How isoflavone levels in common rodent diets can interfere with the value of
      animal models and with experimental results.
AB  - Phytoestrogens are a diverse group of plant-derived compounds structurally or
      functionally mimicking mammalian oestrogens. A variety of effects, in vitro, in
      animal models and in humans, have been attributed to these compounds. It is
      generally not appreciated that many commercial rodent diets are formulated with
      soy as a source of protein and thus large daily doses of phytoestrogens in the
      form of isoflavones are delivered to the animals. The content of isoflavones in
      laboratory diets depends on a number of factors and, therefore, varies
      considerably, both between different formulations, and also from batch to batch
      of the same formulation. Dietary isoflavones can influence a number of different
      endpoints, rendering the dietary levels of such compounds an important
      experimental factor to consider. The levels of isoflavones in common laboratory
      diets are reviewed in relation to the dietary levels influencing different
      endpoints.

PMID- 17234047
TI  - The impact of tail tip amputation and ink tattoo on C57BL/6JBomTac mice.
AB  - Genetic material for polymerase chain reaction (PCR) and Southern blot analysis
      on transgenic mice is normally obtained by tail biopsy. Additionally, it may be
      necessary to tattoo the mice, as it is essential to have a good and permanent
      identification. The aim of this study was to evaluate the effects of amputating
      the tip of the tail to obtain a biopsy for genetic analysis and of ink tattooing
      on welfare in C57BL/6J mice, a strain often used as genetic background for
      transgenes. The behaviour of the animals, fluctuating asymmetry (FA, a measure of
      developmental instability) and the level of restitution in the remaining part of
      the tail were evaluated and used for an assessment of the impact of these
      procedures on the welfare of the animals. One group of mice was marked by tail
      tattooing at various ages. Another group of mice were tail amputated at 12 or 20
      days of age. Body weight and FA were followed, and at the end of the experiment,
      the level of fear/anxiety was assessed using a light-dark box. In the group of
      tail-amputated animals observation of climbing behaviour and a beam walking test
      for balance was performed. Seven weeks after tail amputation, the animals were
      euthanized. The remaining part of the tail was evaluated histopathologically.
      Body weight, behaviour in the light-dark box and balance test results were not
      influenced by tail amputation or tattooing. FA was only transiently increased by
      tattooing. Climbing behaviour was reduced just after tail amputation at 20 days
      of age. No signs of neuromas were found in the amputated tails, but seven weeks
      after amputation a significant number of mice did not have fully regenerated
      glandular tissue and hair follicles in the tail. It is concluded that both tail
      amputation and tail tattooing seem to have minor short-term negative effects on
      welfare and that the tissues on the tail probably do not regenerate fully after
      amputation.

PMID- 17234048
TI  - Should laboratory mice be anaesthetized for tail biopsy?
AB  - Tail biopsies are routinely taken to genotype genetically modified mice. However,
      the effect of this procedure on the wellbeing of the animals has rarely been
      investigated. Thus, it has not yet been clearly demonstrated to what extent the
      mice suffer from tail biopsy (TB) and for how long. The aim of our study was to
      assess the impact of a single TB on the physiological and behavioural parameters
      of adult mice and to investigate whether or not anaesthesia can be beneficial.
      Body weight (BW) curves, daily food/water consumption and telemetric measurements
      of heart rate, body core temperature, and locomotor activity were recorded for
      three days following TB, both with and without anaesthesia with methoxyflurane
      (MOF) or diethylether (ether). Additionally, the impact of anaesthesia alone was
      characterized. TB without anaesthesia induced an increase in heart rate and
      locomotor activity for 1 h. Body core temperature was elevated for 2 h. In
      contrast, heart rate was increased for up to 4 h after anaesthesia. Body core
      temperature remained altered for up to 20 h after exposure to ether and for 44 h
      after exposure to MOF. BW was slightly reduced after MOF. Cases of death occurred
      exclusively under ether at a rate of 7%. Our results indicate a short-lived
      impact of a TB, whereas anaesthesia with either MOF or ether induced remarkable
      alterations in the parameters analysed. In conclusion, these types of anaesthesia
      did not improve mouse wellbeing following tail biopsy.

PMID- 17234049
TI  - Evaluation of the efficacy of a novel electronic pain assessment device, the Pain
      Gauge, for measuring postoperative pain in rats.
AB  - One of the major challenges for individuals working with laboratory animals is
      the recognition and alleviation of pain. The Pain Gauge is marketed as a pain
      assessment device that measures electrodermal activity. To establish whether the
      Pain Gauge is effective in assessing postoperative pain in laboratory rats,
      preoperative and postoperative pain gauge scores ('pain scores') were obtained
      from 67 rats. Rats were randomly assigned to one of three experimental groups
      (laparotomy, craniotomy or control) and to one of four analgesic groups
      (meloxicam [2 mg/kg s.c.] or parecoxib [1, 5 or 20 mg/kg i.v.]). Five consecutive
      'pain scores' were obtained from each animal at each of five time points
      (preprocedure, and at 1, 2, 3 and 4 h postoperatively). Overall there was a
      significant difference between 'pain scores' at different time points; mainly a
      decrease at 1 h postoperatively compared with the preoperative scores. There was
      no overall increase in postoperative 'pain scores' in the rats that were most
      likely to suffer from postoperative pain (rats given a lower dose of analgesic
      that underwent a surgical procedure) compared with rats that did not undergo a
      potentially painful procedure (rats in anaesthesia-only/control group). Therefore
      it was concluded that the Pain Gauge is ineffective in assessing postoperative
      pain in rats in this study.

PMID- 17234050
TI  - Ketamine does not affect intestinal microcirculation in pentobarbital
      anaesthetized rats during experimental endotoxaemia.
AB  - The objective of the study was to evaluate the effects of ketamine on intestinal
      microcirculation in pentobarbital-anaesthetized rats during experimental
      endotoxaemia. A prospective, randomized, controlled study was carried out using
      32 male Lewis rats. The animals were divided into four groups (n = 8 each). All
      animals were initially anaesthetized with 60 mg/kg pentobarbital (i.p.). Group 1
      served as a control (18.5 mg/kg/h pentobarbital i.v.). Groups 2 and 4 received an
      endotoxin intravenous infusion of 15 mg/kg lipopolysaccharide (LPS) from
      Escherichia coli. Groups 3 and 4 also received 10 mg/kg/h ketamine (i.v.). After
      2 h of observation, the animals were examined for intestinal functional capillary
      density (FCD) and leukocyte adherence to the venular endothelium by means of
      intravital fluorescence microscopy (IVM). Subsequent to this examination, blood
      samples were collected to determine release of the cytokines tumour necrosis
      factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10. Endotoxaemia tended
      to decrease intestinal FCD (mucosa: -10.1%, muscularis longitudinalis: -2%,
      muscularis circularis: -9.8%) and significantly increase leukocyte adherence
      within submucosal venules (collecting venules: +133%, postcapillary venules:
      +207%; P<0.05). TNF-alpha, IL-1beta, IL-6 and IL-10 levels were significantly
      elevated following endotoxin challenge. The addition of ketamine to pentobarbital
      anaesthesia did not significantly affect FCD, leukocyte behaviour or cytokine
      levels. In conclusion, intravenous pentobarbital anaesthesia with the additional
      administration of ketamine did not cause alterations within the microcirculation
      or changes in cytokine release during endotoxaemia. In rats, the combination of
      pentobarbital and ketamine is suitable for use during the study of intestinal
      microcirculation in experimental endotoxaemia.

PMID- 17234051
TI  - Induction of heart failure: haemodynamic comparison of three different canine
      models.
AB  - We compared three methods: arteriovenous anastomosis, doxorubicin administration,
      and combination of anastomosis and doxorubicin, with the intention of designing a
      simple, stable model of chronic heart failure. Twelve dogs were divided into
      three groups of four. One group received carotid-jugular anastomosis (Ana
      series), another group received anastomosis and doxorubicin injection (A/D
      series), and the last group received only doxorubicin (Dox series). Animals were
      followed for eight weeks. Fifteen different haemodynamic parameters were tracked
      and compared to baseline values. After eight weeks, diastolic pressure in the
      right atrium increased from 3.8+/-2.0 mmHg at baseline to 5.3+/-5.9 mmHg in the
      Ana series, to 6.3+/-3.3 mmHg in the Dox series and to 8.0+/-2.0 mmHg in the A/D
      series (P<0.05 A/D vs. baseline). Systolic pulmonary wedge pressure increased
      from 11.6+/-2.0 mmHg at baseline to 15.5+/-3.4 mmHg in the Ana series, 14.0+/-3.7
      mmHg in the Dox series and 17.3+/-4.2 mmHg in the A/D series (P = NS vs.
      baseline). Left ventricular ejection fraction decreased from 53.9+/-10% at
      baseline to 36.1+/-5.6% in the Ana series (P<0.05 vs. baseline), 31.5+/-5.4% in
      the Dox series (P<0.05 vs. baseline) and 25.8+/-5.8% in the A/D series (P<0.001
      vs. baseline, P<0.05 vs. Ana series and Dox series). In conclusion, eight weeks
      are not enough to produce stable heart failure using arteriovenous anastomosis
      alone. Doxorubicin administration alone produces a left ventricular failure.
      However, a combination of both of these interventions provides a more stable
      model of right-and left-sided heart failure.

PMID- 17234052
TI  - Anastomotic stenting in a porcine aortoiliac graft model.
AB  - The purpose of the study was to evaluate the feasibility of anastomotic stent
      application in a porcine aortoiliac graft model. In a total of 10 pigs, a
      polytetrafluoroethylene aortobi-iliac graft was implanted through a midline
      abdominal incision. The lower edge of the iliac vessel was graft-inverted about 1
      mm to produce irregularities at the downstream anastomosis. After transverse
      graft incision, six stainless-steel stents, six poly-L-lactic acid (PLLA) stents
      and four PLLA stents with 10% polycaprolactone (PCL) were implanted at the iliac
      anastomotic site using a 6 mm balloon dilatation catheter. Four anastomotic sites
      were left untreated. After two weeks, the patency of graft limbs was evaluated by
      contrast-enhanced computed tomography (CT). Both metal and polymeric stent
      designs provided adequate flexibility to manoeuvre across the anastomotic site
      for expansion in the chosen position. After deployment, the stent-arterial wall
      contact was complete on a macroscopic view. On CT scan, all metal and PLLA
      stented graft limbs were free of stenosis, whereas all PLLA/PCL stents were
      occluded. The non-stented graft limbs showed a stenosis of 50-70%. In summary,
      this model is feasible to assess preclinically the deployment and patency rate of
      an anastomotic stent and to test future stent developments.

PMID- 17234053
TI  - Method of intracranial pressure monitoring and cerebrospinal fluid sampling in
      swine.
AB  - Cerebral oedema and encephalopathy have been noted to occur frequently in
      patients severely ill or dying after trauma, ischaemia, infections or even
      metabolic disorders. The objective of the present study was to establish
      continuous monitoring of the intracranial pressure (ICP) and sampling of
      cerebrospinal fluid (CSF) for further investigations in swine. ICP monitoring was
      established in eight pigs by using a ventricular drainage system, implemented
      after paramedian trepanation of the os frontale. CSF and serum samples were taken
      for measurement of the levels of glucose and protein. Operating time was 21+/-8
      min for the trepanation until ICP monitoring was performed. No complications
      occurred during surgery. Continuous monitoring of ICP and CSF sampling was easy
      to perform, and without any side-effects in any animal. At autopsy, no iatrogenic
      lesions were found and monitoring catheters were still in place. For several
      types of research requiring ICP monitoring and sampling of CSF, this method can
      be used successfully.

PMID- 17234054
TI  - Weekend versus working day: differences in telemetric blood pressure in male
      Wistar rats.
AB  - Blood pressure (BP) is a frequently monitored parameter in research. Various
      methods are used to obtain BP values in animal models, but telemetry is the
      method of choice because it allows for continuous monitoring in conscious and
      freely moving animals. However, factors due to the animal facility, like
      activities and sound, can still influence measurements. We, therefore,
      retrospectively compared BP values in adult male Wistar rats during working hours
      with values from non-working days. Telemetry devices were implanted according to
      standard protocol. Values were obtained at the age of 6 and 12 months during
      working hours (Friday 10:00-16:00 h, lights on 06:00-18:00 h) and compared with
      data from the average of Saturday 10:00-16:00 h and Sunday 10:00-16:00 h,
      representing non-working days. Data were available from 12 and 7 rats at 6 months
      and 12 months of age respectively. Relative differences in heart rate,
      spontaneous locomotor activity, systolic and diastolic BP were 2.2% (P<0.001),
      32.9% (P<0.05), 3.2% (P<0.05) and 3.7% (P<0.05), respectively, with no
      differences between the age groups. We have shown a significant and important
      difference between BP values obtained during working hours and non-working days
      using telemetry in adult male Wistar rats. This phenomenon has implications for
      the interpretation of BP measurements in animals.

PMID- 17234055
TI  - The effect of preweaning and postweaning housing on the behaviour of the
      laboratory mouse (Mus musculus).
AB  - Standard housing for laboratory mice severely restricts natural behaviour and the
      control that the animal has over its environment. Providing the cage with objects
      is a method that has been used to both increase environmental complexity, promote
      the performance of natural behaviour and provide greater controllability for the
      animal. This method of furnishing cages has mostly been studied in adult animals,
      and little is known about the influence that the preweaning environment has on
      the behaviour of mice as adults. This study aimed to investigate the effects on
      mice behaviour of preweaning and postweaning housing environment. In this
      experiment, 64 pairs of animals of the strain C57BL/6J were used. Half of the
      animals were born and reared until weaning in standard cages and the other half
      in cages twice the size of the standard and furnished with nesting material, a
      cardboard tube, a PVC nest box and a wooden chewblock. After weaning, half the
      animals in each group were changed to the other type of cage, whereas the other
      half remained in the same environment; in both cases they were kept in single-sex
      pairs of littermates. Behaviour during the dark, active period was studied
      through video recordings. We found no main effects of preweaning environment on
      behaviour; however, mice moved from furnished to standard cages at weaning showed
      a decrease in inactive behaviour at four weeks of age. Mice housed after weaning
      in standard cages spent less time inactive, and more time engaging in activities
      like feeding and drinking, self-grooming and allogrooming. A sex difference was
      also found, in that females showed a greater performance of exploratory behaviour
      as well as a greater prevalence of stereotypies. The use of different objects and
      locations within the furnished cage was also analysed at both ages. Results show
      that at eight weeks of age mice spent more time at the top of the cage, and that
      the use of the nest box (although not for resting) increased between four and
      eight weeks. Mice were found to use the nest box as a nesting site/sleeping place
      only at age four weeks, whereas they always used the nesting material for
      sleeping.

PMID- 17234056
TI  - Rederivation of Helicobacter hepaticus-infected Mongolian gerbils by Caesarean
      section and cross-fostering to rats and mice.
AB  - The Mongolian gerbil serves as an animal model for a wide range of diseases. As
      these animals are extensively used for the study of Helicobacter pylori-induced
      gastritis, naturally occurring infections with rodent Helicobacter species in
      gerbils are a possible source of interference in studies of H. pylori-associated
      disease. The gerbil stock at the Central Animal Facility in Hannover was
      persistently infected with H. hepaticus. The aim of this study was to derive
      Helicobacter species-free Mongolian gerbils. Therefore, germfree gerbil pups were
      obtained by Caesarean section and the pups were transferred to female rats and
      mice with recently delivered litters. In total, four Ztm:NMRI mice, four Ztm:SPRD
      rats and one DA/Ztm rat that originated from a specified pathogen-free area were
      selected to serve as foster mothers. With this approach, it was possible to
      obtain Helicobacter-free gerbils. Rearing by mice was more successful than by
      rats, as six of nine gerbils were reared by mice, but only one of 29 gerbils was
      reared by rats.

PMID- 17234057
TI  - Anthropometrical parameters and markers of obesity in rats.
AB  - The present study was undertaken to determine anthropometrical parameters in male
      adult Wistar rats. We tested the hypothesis that the anthropometrical index may
      identify obesity and may predict its adverse effects on lipid profile and
      oxidative stress in rats. Two experimental protocols were performed. In the first
      experiment, 50 male Wistar rats, 21 days old and fed a control chow were studied
      up to 150 days of age. In the second experiment, male Wistar rats, 60 days old,
      were divided into three groups (n = 8): control (C) given free access to a
      control chow; (S) receiving the control chow and drinking 30% sucrose ad libitum
      and (HC) fed a high-carbohydrate diet ad libitum. The first experiment showed
      that food consumption, energy intake and body weight increased with increasing
      age, while specific rate of body mass gain was significantly decreased. There
      were no significant differences in body length and thoracic circumference of rats
      from 60 days of age. The abdominal circumference (AC) and body mass index (BMI)
      significantly increased with enhancing age in rats up to 90 days of age and
      remained constant thereafter. In the second experiment, after 30 days of dietary
      treatment, the final body weight, body mass gain, carcass fat and BMI were higher
      in S and HC rats than in C. There were no significant alterations in body length
      and carcass protein among the groups. Triacylglycerol (TG), total cholesterol
      (CT), low-density lipoprotein cholesterol (LDL-C) and lipid hydroperoxide (LH)
      were higher in S and HC rats than in C. High-density lipoprotein cholesterol (HDL
      C) decreased in HC rats and total antioxidant substances (TAS) decreased in S and
      HC rats. There were positive correlations between BMI with carcass fat, BMI with
      LH and BMI and serum TG concentration. In conclusion, the BMI for male adult
      Wistar rats ranged between 0.45 and 0.68 g/cm(2). Obesity may be easily estimated
      from the BMI in rats. Alterations in BMI were associated with dyslipidemic
      profile and oxidative stress in serum of rats and BMI may predict these adverse
      consequences of the obesity in rats.

PMID- 17234058
TI  - Visual documentation of ovine pituitary gland development with magnetic resonance
      imaging following zeranol treatment.
AB  - The objective of the current study was to determine whether magnetic resonance
      imaging (MRI) could be successfully utilized to document the effect of an
      oestrogenic anabolic agent on pituitary gland growth. The experimental animals
      consisted of two 1/2 sibling Suffolk wethers (castrated rams), which received
      either no implant (control, n = 1) or a 24 mg zeranol implant at day 0 and day 42
      (zeranol; n = 1). Animals were anaesthetized with propofol and supported with
      oxygen during the MRI procedure. A mobile MRI unit with a 0.5 tesla (T),
      superconducting magnet was used to obtain 3 mm thick, non-contrast enhanced, T1
      weighted (TR 500-600, TE25) sagittal, transverse and dorsal images of the
      pituitary gland. Sagittal images were recorded only when the mesencephalic
      aqueduct and infundibulum were distinctly visible in the same image. Pituitary
      glands were imaged at 14-day intervals for 70 days to determine if and when the
      anabolic effects of zeranol on pituitary gland growth could be visualized using
      MRI techniques. Three separate measurements of the pituitary gland dimensions
      made with the on-screen cursor were averaged to calculate pituitary gland
      dimensions and volume. A computer-assisted image analysis system and laser film
      images were used to determine pituitary gland area. Increases in pituitary gland
      volume for control and zeranol-treated animals were evident within 14 days, and
      by the end of the 70-day study, the increase in pituitary volume for the zeranol
      treated animal was three times greater than that of the control animal. Overall,
      our results indicate that MRI technology can be successfully used to document the
      development of the pituitary gland in vivo. Application of knowledge gained from
      this novel approach to study the growth, development and function of endocrine
      glands over time, and within the same animal, will enhance human and animal
      endocrine diagnostic procedures.

PMID- 17234059
TI  - A novel and simple method for endotracheal intubation of mice.
AB  - Endotracheal intubation in mice is necessary for experiments involving
      intratracheal instillation of various substances, repeated pulmonary function
      assessments and mechanical ventilation. Previously described methods for
      endotracheal intubation in mice require the use of injection anaesthesia to
      immobilize the animal during the intubation procedure or the use of a volatile
      anaesthetic prior to intubation for immobilization. With these methods, the
      control of anaesthetic depth during the intubation procedure is absent. We
      describe a method for simple and rapid intratracheal intubation in mice for
      mechanical ventilation, using a self-built plastic support to facilitate the
      intubation procedure. General anaesthesia is maintained by means of inhalation
      through a non-rebreathing circuit connected to the plastic support. This set-up
      gives the operator control of anaesthetic depth and sufficient time to perform
      the intubation procedure. A purpose-made laryngoscopic blade is used to
      facilitate the intubation tube entering the trachea. The blade of the purpose
      made laryngoscope is constructed as a retraction guide and is curved for easy
      handling. Under direct vision, the epiglottis is gently lifted by the
      laryngoscopic blade while the intubation tube is pushed into the trachea.
      Following this novel intubation technique, we were able to mechanically ventilate
      mice for at least 2 h without severely disturbing blood gases. Histological
      evaluation of the lungs and microscopic evaluation of the trachea and larynx
      showed no signs of trauma related to the intubation technique or mechanical
      ventilation.

PMID- 17234060
TI  - Spontaneous trichoepithelioma in a laboratory mouse: gross, microscopic and
      immunohistochemical findings.
AB  - A spontaneous trichoepithelioma occurred in a Swiss OF1 outbred, four-month-old,
      intact, nulliparous female mouse from a breeding colony. At necropsy, the tumour
      was a single, well-delineated mass measuring 4.2 cm in major diameter, located in
      the thoracic region and had an intact haired surface. The regional lymph nodes
      were not enlarged and no other abnormalities were found. Microscopically, it was
      composed of a random admixture of budding epithelial islands and cystic
      structures variable in size. The epithelial islands were composed of basaloid
      cells. The cystic structures were lined by squamous epithelium with or without a
      granular cell layer and contained lamellar or amorphous keratin, as well as wide
      areas of matrical keratinization (ghost cells) with or without a peripheral layer
      of basaloid cells and calcified contents. Mitotic activity of basaloid cells was
      moderate to high, but nuclear or mitotic atypia were not observed. High and low
      molecular weight cytokeratins, profilaggrin and involucrin expression were
      observed in the tumour. The immunohistochemical profile of this rare type of
      tumour of the skin of mice, which includes a first-time description of involucrin
      expression, confirms the histological evidence of differentiation towards more
      than one segment of follicular epithelium.

PMID- 17234063
TI  - Tracking outcomes in surgical care.

PMID- 17234064
TI  - How a visit to the museum can contribute to professional awareness during medical
      school.

PMID- 17234065
TI  - Management of spleen injuries in the adult trauma population: a ten-year
      experience.
AB  - BACKGROUND: Increasing awareness of the postoperative risks associated with
      splenectomies has led physicians and surgeons to use an alternative nonoperative
      strategy in handling traumatic spleen injuries. Our primary objective was to
      compare clinical outcomes between operative and nonoperative managements in adult
      patients with blunt splenic injuries. The secondary objective was to assess the
      changes in the patterns of managing splenic injuries in the past 10 years.
      METHODS: We performed a retrospective chart review on 266 adult patients with a
      spleen injury who were admitted to a tertiary trauma centre in Ontario between
      1992 and 2001. We grouped and compared the patients according to the treatment
      received, either operative or nonoperative. Frequencies and confidence intervals
      are reported. Categorical variables were compared with chi-square or Fisher's
      exact tests. Continuous variables were reported as median and quartile (Q) and
      were compared with the nonparametric Mann-Whitney U test. RESULTS: Of 266
      patients, 118 had surgery and 148 were managed nonoperatively. The mortality rate
      was similar between operative and nonoperative groups (9.3% v. 6.8%, p = 0.49),
      respectively. The rate of any complication was 47.9% for the operative group and
      37.9% for the nonoperative group. The median length of stay in hospital was
      significantly higher in the operative group than in the nonoperative group (21.0
      [Q 11.0-40.5] v. 14.0 [Q 7.0-31.5] d, p < 0.001), respectively. This difference
      was more likely related to a higher proportion of patients having injury severity
      scores greater than 25 in the operative group. The rate of nonoperative
      management of spleen injuries was significantly increased from 48.5% to 63.1%
      between 1992-1996 and 1997-2001 (p = 0.02). CONCLUSION: The present study has
      shown that nonoperative management of blunt spleen trauma has increased over time
      and has acceptable mortality and complication rates in selected patients.
      Additional prospective studies are needed to assess the feasibility and safety of
      nonoperative management in adult spleen injuries. Furthermore, the management of
      traumatic spleen injuries with respect to associated injuries, such as head
      injuries or intra-abdominal injuries, needs ongoing evaluation.

PMID- 17234066
TI  - The effect of spinal anesthesia on blood transfusion rate in total joint
      arthroplasty.
AB  - BACKGROUND: Total joint arthroplasty (TJA) patients often receive allogeneic
      blood transfusion. The use of regional anesthesia (RA) is thought to protect
      against the need for blood transfusion, but many randomized trials of RA in TJA
      have not reached this conclusion unanimously. We sought to describe the effect of
      RA on allogeneic transfusion in a large retrospective TJA series. METHODS: We
      examined data from all TJAs performed in Edmonton, Alberta, in the year 2000 (n =
      1875) and used logistic regression modelling to determine the relation between
      the use of RA and allogeneic transfusion. RESULTS: Twenty-eight percent of TJA
      subjects received an allogeneic transfusion. Transfusion was independently
      associated with increasing age, decreasing body mass, decreasing preoperative
      hemoglobin, female sex, increased comorbidity and prolonged operative time. After
      controlling for these factors, we found that the use of RA (in the form of spinal
      anesthesia) compared with general anesthesia reduced the odds ratio (OR) for
      transfusion to 0.729 (95% confidence interval [CI] 0.559-0.949). This represents
      the combination of a strong relation between RA and transfusion prevention in hip
      arthroplasty (OR 0.646, 95% CI 0.443-0.944) and a nonsignificant relation in knee
      arthroplasty (OR 0.825, 95% CI 0.564-1.208). CONCLUSION: The use of spinal
      anesthesia protects against allogeneic transfusion in arthroplasty of the hip but
      not the knee. This is consistent with what is known about the hemodynamic
      consequences of spinal anesthesia.

PMID- 17234067
TI  - Infectious complications following laparoscopic appendectomy.
AB  - INTRODUCTION: A meta-analysis of the literature suggests there is an increased
      rate of intra-abdominal abscess after laparoscopic appendectomy (LA) compared
      with open appendectomy (OA). METHODS: To analyze the infectious complications of
      LA at one tertiary care centre, we completed a retrospective chart review for all
      patients undergoing LA for acute appendicitis from 1995 to 2002. RESULTS: We used
      established exclusion criteria to identify 175 patients with a mean age of 37.6
      (standard deviation [SD] 14.5) years (95 male, 80 female). The mean operating
      time was 61.9 (SD 22.5) minutes. Excluding conversions to OA (14/175, 8%),
      operating time was 59.9 (SD 20.5) minutes. On surgical assessment, 143 patients
      had acute nonperforated appendicitis (17 perforated, 15 gangrenous). However, on
      histopathology assessment, 13 cases of normal appendix were identified (13/175,
      7.4%). The overall median length of stay was 2.0 days. Three patients had
      significant postoperative infectious complications, including 1 wound infection
      and 2 cases of intra-abdominal abscesses. All abscesses were managed successfully
      with percutaneous drainage. An analysis of perioperative factors that might have
      contributed to the infectious complications revealed that each case of
      postoperative intra-abdominal abscess occurred in patients with gangrenous
      appendicitis and when extensive irrigation was used during LA. CONCLUSIONS: An
      institutional review demonstrates outcomes comparable with the Cochrane
      systematic review of the published literature. Technical issues that may impact
      on intra-abdominal abscess formation after LA include aggressive manipulation of
      the infected appendix and increased use of irrigation fluid, possibly producing
      greater contamination of the peritoneal cavity.

PMID- 17234068
TI  - Foot rotational effects on radiographic measures of lower limb alignment.
AB  - INTRODUCTION: Surgical planning of high tibial osteotomy (HTO) typically requires
      the measurement of lower limb alignment from standing anteroposterior
      radiographs. Although every effort is made to maintain a standardized patient
      position, factors such as pain or anatomic constraints may necessitate acquiring
      the radiograph in a less than optimal patient position. One such constraint is
      natural rotation of the feet with respect to the tibia. The purpose of the
      present study was to investigate the magnitude of the effect of foot rotation on
      radiographic measures of lower limb alignment. METHODS: We analyzed 19 lower
      limbs from radiographs obtained from 10 people who reported to an orthopedic
      injuries clinic. Each patient was radiographed in 3 positions: 15 degrees of
      internal foot rotation, no foot rotation and 15 degrees of external foot
      rotation. We measured and compared the mechanical axis angle (hip-knee-ankle) and
      the mechanical axis deviation from each position. RESULTS: Compared with the
      position with no foot rotation, internal foot rotation resulted in less measured
      varus alignment and less mechanical axis deviation from the knee joint centre,
      whereas external foot rotation produced greater measured varus alignment and
      increased mechanical axis deviation from the knee joint centre. CONCLUSIONS:
      These results indicate that patient positioning is an important factor when
      measuring lower limb alignment from radiographs. As a result, special care must
      be taken when acquiring these radiographs for use in planning surgical procedures
      such as HTO.

PMID- 17234069
TI  - Influence of cementless femoral stems inserted in varus on functional outcome in
      primary total hip arthroplasty.
AB  - INTRODUCTION: Historically, cemented total hip arthroplasty (THA) femoral stems
      inserted in varus have yielded poor clinical results. Few studies to date have
      addressed the question of the effects of varus alignment on cementless stems. We
      conducted a retrospective review of 125 uncemented THA femoral stems implanted by
      a single surgeon from 1994 to 1999. METHODS: We conducted a retrospective
      radiographic review of 125 cementless primary THA femoral stems implanted by a
      single surgeon who used the Watson-Jones approach; we identified 16 stems
      implanted in varus, defined as >or= 5 degrees and thus analyzed the effect of
      varus alignment on functional outcome. We matched varus stems to a cohort of 16
      nonvarus cementless stems and measured radiographic signs of loosening and
      subsidence, defined as > 2 mm. RESULTS: At 4 years postsurgery, there was no
      significant difference in range of motion or in Harris Hip Score (p > 0.5), and
      no cases showed evidence of radiographic loosening or subsidence (p = 0.226).
      CONCLUSIONS: Study results suggest there is no consequence of varus femoral
      alignment in the cementless stems. Although it is not recommended to implant
      stems in varus, there were no apparent radiographic or clinical consequences
      observed at up to 4 years postoperative in this small case series.

PMID- 17234070
TI  - Visual-spatial ability, learning modality and surgical knot tying.
AB  - INTRODUCTION: The ability to mentally rotate an object in 3 dimensions has been
      shown with an individual's score on the Vandenberg and Kuse Mental Rotations
      Test. The was to determine whether this Mental Rotations Test could be used to
      predict performance complex surgical skill - the tying of a 1-handed surgical
      reef knot. In addition, we learning a spatially complex surgical skill could be
      achieved more effectively via a computer-based selfdirected learning approach
      than with a didactic lecture-based teaching method. METHODS: preclerkship medical
      students at the University of Western Ontario were randomized into computer-based
      self-directed learning group and a didactic lecture-style learning group.
      administration of the Mental Rotations Test, the students were taught how to tie
      a reef knot via the learning modality assigned to their respective group.
      RESULTS: Students Mental Rotations Test scores were able to tie more surgical
      knots in the allocated time Students learning how to tie the surgical knot via
      the computer-based self-directed showed improvement on their knot tying abilities
      more rapidly than their didactically trained colleagues. CONCLUSION: The ability
      to mentally rotate an object in 3 dimensions played an important initial learning
      of a spatially complex surgical technical skill. Our data demonstrated learning
      was as effective and more practical than traditional lecture-based learning.

PMID- 17234071
TI  - Early results after laparoscopic Roux-en-Y gastric bypass: effect of the learning
      curve.
AB  - INTRODUCTION: This study was performed to evaluate the safety and short-term
      efficacy of laparoscopic Roux-en-Y gastric bypass (LRYGB) for morbid obesity and
      to describe the relation between learning curve and short-term outcomes. METHODS:
      We collected a prospective database on the first 201 consecutive patients who
      underwent LRYGB by a single university-based, experienced bariatric surgeon over
      24 months. We divided patients into 3 consecutive groups of 67 patients for
      analysis (Group 1, Group 2 and Group 3). RESULTS: The mean patient age was 37
      (standard deviation [SD] 9) years; mean body mass index (BMI) was 49.2 (SD 8.3)
      kg/m2. BMI was similar in Groups 1 and 2 (mean 47.1, SD 5.9 and mean 48.7, SD 8.9
      kg/m2) but increased in Group 3 (mean 52, SD 9.7 kg/m2, p < 0.01). Operative time
      decreased from 145 (SD 30) minutes in Group 1 to 114 (SD 24) minutes in Group 2
      (p < 0.01) and was maintained at 119 (SD 23) minutes in Group 3. Early and late
      complication rates were 14.9% and 12.4%, respectively. Leak rates decreased from
      6.0% in the first group to 1.5% in Groups 2 and 3, but they did not reach
      statistical significance. Anastomotic stricture rates decreased from 11.9% in
      Group 1 to 3.0% in Group 2 (p < 0.01). Overall excess weight loss for the entire
      series was 31.5% (SD 11.9%), 54.5% (SD 14.1%), 77.1% (SD 18.5%) and 82.1% (SD
      17.5%) at 3, 6, 12 and 18 months, respectively. CONCLUSION: LRYGB can be
      performed with acceptable morbidity and short-term results during the learning
      curve. In our series, operative time and anastomotic stricture rates decreased
      with experience, despite an increase in mean BMI.

PMID- 17234072
TI  - Initial clinical outcomes after completion of training in a Canadian Royal
      College thoracic surgery program.
AB  - BACKGROUND: Thoracic procedures are currently performed by general and thoracic
      surgeons. Initial clinical outcome after training is a good measure of the
      quality of the surgical training received. METHODS: We examined the morbidity and
      mortality for pneumonectomy, lobectomy and esophagectomy during one surgeon's
      first 2 years of practice; we collected data prospectively. The results were
      based on the experience of the only dedicated thoracic surgeon (5 years of
      general surgery and 3 years of thoracic surgery training with certification from
      the Royal College of Physicians and Surgeons of Canada) at the largest tertiary
      care hospital of Brown University School of Medicine. RESULTS: During the 2-year
      period, 154 major pulmonary resections (20 pneumonectomies, 134 lobectomies) and
      25 esophagectomies (18 transhiatal, 4 Ivor-Lewis, 2 thoracoabdominal, one 3
      incision) were performed. Mortality for major lung resection was 1.9%
      (pneumonectomy 5%, lobectomy 1.5%), and morbidity was 27% (pneumonectomy 35%,
      lobectomy 26%). Mortality for esophagectomy was 4%, and morbidity was 36%
      (anastamotic leak 12%). CONCLUSIONS: These results compare favourably with
      clinical outcomes published from several large series. Thoracic surgical training
      in Canada is adequate and prepares surgeons well to perform major thoracic
      procedures. A database of the initial results from all graduates of thoracic
      surgery training in Canada is needed. Such a database could be used to compare
      the initial results of thoracic procedures performed by general and thoracic
      surgery graduates from Canada and the United States.

PMID- 17234073
TI  - Granulomatous mastitis including breast tuberculosis and idiopathic lobular
      granulomatous mastitis.

PMID- 17234074
TI  - Evidence-based surgery. Canadian Association of General Surgeons and American
      College of Surgeons Evidence Based Reviews in Surgery. 19. The effect of a
      decision aid on knowledge and treatment decision making for breast cancer.

PMID- 17234075
TI  - Surgical images: musculoskeletal. Multidirectional acromioclavicular joint
      instability posttrauma.

PMID- 17234076
TI  - Radiology for the surgeon. Soft-tissue case 59. Giant epidermal cyst of the
      ischiorectal fossa.

PMID- 17234077
TI  - Successful damage control of complex vascular and urological gunshot injuries.

PMID- 17234078
TI  - Barogenic esophageal rupture: Boerhaave syndrome.

PMID- 17234079
TI  - [Quality of life in gastrointestinal cancer: what is the impact of nutrition?].
AB  - INTRODUCTION: Nutrition and Quality of Life (QoL) are key issues. AIMS: 1) to
      evaluate Quality of Life (QoL), nutritional status and dietary intake, taking
      into account the stage of disease and therapeutic interventions, 2) to determine
      potential inter-relations, 3) to quantify the relative contributions of
      cancer/nutrition/treatments on QoL. METHODS: In 184 oesophagus, stomach and
      colon/rectum cancer patients, the following were evaluated: QoL (European
      Organisation for Research and Treatment of Cancer Quality of Life Questionnaire),
      nutritional status (% weight loss over the previous 6 months), usual diet (diet
      history), current diet (24 hr recall) and a range of clinical variables. RESULTS:
      Stage III/IV patients showed a significant reduction from their usual
      energy/protein intake (p=0.001), worse in oesophagus (p=0.02), while current
      intakes were lower than in stage I/II patients (p=0.0002). Weight loss was
      greater in stage III/IV (p=0.001). Different diagnoses and cancer stages
      presented different patterns of QoL function scales (p=0,03), significantly and
      independently associated with nutritional factors (p=0,05). Patients in stage
      III/IV had increased symptomatology (p=0,003); symptom scales and single items
      were strongly associated with stage III/IV (p=0,04). Patients with stomach cancer
      presented the worst global QoL not significantly different from oesophagus, vs
      colon/rectum, p=0,02. CONCLUSIONS: In oesophageal, stomach and colon/rectum
      cancer, nutritional deterioration depends of diet intake, the latter is mainly
      determined by cancer location and stage. Patients' QoL was determined by cancer
      or nutrition-related factors with distinct relative weights. Due to this
      multidimensional construct, in which nutrition plays a major role, nutritional
      therapy must be integrated in early stages of the overall treatment.

PMID- 17234080
TI  - Haemodynamic parameters obtained by transthoracic echocardiography and Swan-Ganz
      catheter: a comparative study in liver transplant patients.
AB  - OBJECTIVE: To compare the haemodynamic measurements of cardiac output (CO),
      central venous pressure (CVP), pulmonary capillary wedge pressure (Pw) and
      pulmonary artery systolic pressure (PASP), obtained by Swan-Ganz catheter and
      transthoracic echocardiography. MATERIAL AND METHODS: Prospective study in a
      Medical/Surgical Intensive Care Unit (ICU). A total of 41 post liver transplant
      patients were enrolled. CO, CVP, Pw and PASP, were simultaneously determined by
      two independent observers, utilizing a Swan-Ganz catheter and transthoracic
      echocardiography, using equations described in the literature. A linear
      correlation and a Bland-Altman analysis were performed. RESULTS: A good
      correlation between invasive and non- invasive measurements for CO (r=0.97) and
      CVP (r=0.88) was found, but determinations of Pw (r=0.41) and PASP (r=0.18) did
      not correlate well. Bias and 95% confidence interval for CO were negligible
      namely when a CO<6 l/min was considered. Pulsed-wave Doppler-echocardiography
      underestimates the CO when compared with thermodilution, but the 2 techniques
      agree on average and can be used interchangeably. CONCLUSIONS: The non-invasive
      determination of CO in critical care post liver transplant patients correlates
      well with the invasive determinations. Transthoracic echocardiography was not
      appropriate for calculating filling parameters studied. Although the data was
      obtained in post liver transplant patients, they could be useful in defining the
      role of echocardiography in the ICU.

PMID- 17234081
TI  - [Chorioamnionitis and neonatal morbidity].
AB  - INTRODUCTION: Several studies highlight the association between perinatal
      infection/inflammation and neonatal morbidity, mainly bronchopulmonary dysplasia
      and periventricular leukomalacia. AIM: To evaluate the role of histological
      chorioamnionitis on the overall morbidity of preterm newborns. METHODS: A
      retrospective study on preterm newborns less than 34 weeks gestational age at
      birth, and respective mothers, at three tertiary medical centers (Hospital de Sao
      Joao, Maternidade Julio Dinis and Centro Hospitalar de Vila Nova de Gaia) in the
      north of Portugal, between January 2001 and December 2002. We evaluated the
      association between histological chorioamnionitis and the overall neonatal
      morbidity. The association between histological chorioamnionitis and acute
      (respiratory distress syndrome) and chronic (bronchopulmonary dysplasia) lung
      damage was also evaluated in the subgroup of less than 1000 g birthweight preterm
      neonates. RESULTS: 452 [ M 253 / F 217; birthweight 1440 (515-2620) g;
      gestational age 31 (23-33) weeks] preterm newborns were included. The association
      between histological chorioamnionitis and the overall neonatal morbidity was:
      respiratory distress syndrome OR 1.5 (95% CI 0.94-2.31); bronchopulmonary
      dysplasia OR 2.6 (95% CI 1.16-6.03); patent ductus arteriosus OR 2.5 (95% CI 1.17
      5.44); sepsis OR 1.2 (95% CI 0.9-2.13); necrotizing enterocolitis OR 1.4 (95% CI
      0.9-1.76); intraventricular hemorrhage grades III-IV OR 2.5 (1.20-5.11); cystic
      periventricular leukomalacia OR 3.0 (1.5-6.07); retinopathy of prematurity OR 1.4
      (95% CI 0.8-1.35). The association adjusted to birthweight and gestational age
      was: bronchopulmonary dysplasia OR 1.2 (95% CI 0.51-2.95); patent ductus
      arteriosus OR 0.9 (95% CI 0.4-2.35); intraventricular hemorrhage grades III-IV OR
      0.9 (95% CI 0.39-2.28); cystic periventricular leukomalacia OR 2.2 (95% CI 1.03
      4.61). The association between histological chorioamnionitis and lung damage in
      the subgroup of less than 1000 g birthweight preterm neonates was: respiratory
      distress syndrome OR 0.23 (95% CI 0.01-2.51); bronchopulmonary dysplasia OR 1.61
      (95% CI 0.38-6.97). CONCLUSION: This study confirms the association between
      histological chorioamnionitis and cystic periventricular leukomalacia of the
      preterm newborn.

PMID- 17234082
TI  - [Six clinical cases of relapsing polychondritis: review].
AB  - INTRODUCTION: Relapsing Polycondritis is a rare connective tissue disease of
      unknown aetiology that is manifested by inflammatory changes in cartilaginous
      tissues but the immune damage can spread and involve other tissues. MATERIAL AND
      METHODS: Six patients with relapsing poycondritis treated in our service, between
      1990 and 2003, were reviewed. The clinical features, age of onset, time from
      onset to diagnosis, disease associations and treatment were focused. RESULTS: The
      female-to-male ratio in our series was 2:4, The median age onset of symptoms was
      52 years. A diagnosis delay varied from 8 months to 4 years, with a median time
      of 18 months. All the five patients had auricular and nasal condritis,
      laringotracheal involvement was detected in four patients, arthralgia and
      arthritis also in four patients, cardiac involvement was present in two patients,
      myelodysplastic syndrome in one patient and ocular disease in four patients.
      CONCLUSION: This is small sample study that differs from other studies in sex
      distribution. This disease is more frequent in females and in our sample men were
      more affected. The clinical manifestations and disease associations were similar
      to other populations. Calling attention is the best way to diminish time to
      diagnosis of this rare pathology.

PMID- 17234083
TI  - [Intrathecal baclofen in treatment of spasticity casuistry of the Centro
      Hospitalar de Coimbra].
AB  - INTRODUCTION: The neuromotor techniques do not have good results in severe
      spasticity prevention and treatment (Ashworth Scale > or = 3). High doses of oral
      Baclofen are required, thus intrathecal baclofen is a current alternative.
      OBJECTIVES: To assess the effectiveness of treatment, the eight Spinal Cord
      Injury (SCI) patients with a intrathecal baclofen pump are controlled in a
      specific consultation in the Rehabilitation Service of C.H.C. The authors analyse
      the results and made a bibliographic review. METHODS: Medline research and
      retrospective study through the analysis of the individual clinical file.
      RESULTS: Intrathecal baclofen is effective in severe spasticity when oral
      baclofen is ineffective or when intolerable side effects occur. In our study
      group of nine patients, one had infection to the material in the Baclofen pump,
      and in the other eight patients was observed improvement of spasticity: six were
      re-classified grade 2 and two were re-classified grade 3 (Modified Ashworth
      Scale). CONCLUSION: Intrathecal baclofen infusion is an effective therapeutic
      alternative in severe spasticity due to spinal cord lesions. With this method,
      adequate liquor concentrations for hyperactivity/hipertonicity reduction are
      possible without the normal side effects that occur with the high oral dosage
      (about 100 times higher).

PMID- 17234084
TI  - [Breast pathology: evaluation of the Portuguese scientific activity based on
      bibliometric indicators].
AB  - INTRODUCTION AND OBJECTIVES: The bibliometric analysis of the Portuguese
      scientific production in the field of breast pathology since 1995 to date (July
      2005) provides an overview on the developed scientific activity on this subject
      and allows the characterisation of some relevant features as well as its
      evolution along the studied period. MATERIAL AND METHODS: Documents collected,
      reflecting the national scientific production in the field of breast pathology
      between 1995 and July 2005 in 3 databases, Medline (with search interface
      PubMed), Science Citation Index and Index of the Portuguese medical journals were
      studied. We applied quantitative and qualitative bibliometric indicators to the
      found number of articles and the journals where they were published. The
      quantitative indicators based on the number of published articles illustrate
      Portugal's position in the area of breast pathology within the international
      scientific community; further, it also allows the identification of the
      participation of the different institutions and national bodies, allocated by
      geographic areas, in scientific production as well as the establishment of
      international collaboration. Qualitative indicators were used to investigate the
      influence, and the impact of the scientific production. These are indicators
      based on the journal classification where the articles were published and also
      the citations they received. The number of citations obtained by the articles
      collected in the performed search, was determined, based on the Science Citation
      Index and the Impact Factor (IF) of the journals, which is annually published in
      the Journal Citation Reports (JCR). In spite of all its constraints, it is
      difficult not to accept the opinion that the Impact Factor is today one of the
      few means (if not the sole one) which enables an assessment of the influence of a
      journal in the international scientific community. RESULTS: During the evaluated
      period, the Portuguese scientific production in the selected area showed an
      increase of 200%. We analysed 348 documents (232 published in the selected
      international Databases and 16 in the national Database. We noticed that articles
      published by one single author are very rare, n=6 and that co-authorship is the
      most common way of publishing. The distribution of article production is as
      follows: 59% in the North Zone, 26% in the South Zone and 15% in the Central Zone
      of the country. The national institutions with a higher rate of publishing in
      renowned international journals are IPATIMUP, IPO Porto and IPO Lisboa. The
      institutions which publish the larger number of papers in Portuguese journals are
      Hospitals and Health Centres. The international journals selected by the national
      scientists present a high impact factor. In the whole of the 232 articles
      selected in the international databases, 81 have not received any citation and
      120 obtained a total of 1.856 citations. It should be noted that the more recent
      articles have not yet received citations. The articles resulting from
      international collaboration, were those receiving an higher rate of citations.
      CONCLUSIONS: An increase of the investigation in breast pathology is observed,
      this being illustrated by the increase in the number of articles published in
      well-recognized international journals. It is also noticed a trend to publish in
      journals with a higher impact factor as well as an increasing role of co
      authorship and international collaboration.

PMID- 17234085
TI  - [Medical error in diagnostic imaging, performance and CAD systems].
AB  - Error occurs in medical practice. Perception error is particularly prevalent in
      Radiology. The studies in this area of knowledge are vital to understand the
      importance of perceptual factors in diagnostic imaging and consequently providing
      information allowing the development of computerized aided detection systems (CAD
      systems), that can help to reduce the number of false-negatives.

PMID- 17234086
TI  - [Benzodiazepine's utilization in continental Portugal (1999-2003)].
AB  - INTRODUCTION: Portugal has one of the highest levels of benzodiazepine's
      utilization at European level. This issue was highlighted on the latest
      International Narcotics Control Board report, which advises Portugal to analyse
      the actual procedures on prescription and utilization of these drugs. This study
      aimed to analyse Portuguese benzodiazepine's utilization patterns and trends at
      regional and national level, and analyse its relation with factors known to
      affect the utilization of these drugs. METHODOLOGY: Drug utilization data refers
      to the drugs prescribed and dispensed in the ambulatory to the population covered
      by the National Health Service, from 1st January 1999 to 31st December 2003. Data
      was expressed in Defined Daily Dose (DDD) per 1000 inhabitants per day (DHD).
      RESULTS: In the Portuguese National Health Service during the period in study
      there was a decrease of 1.2% on benzodiazepine's utilization. Nevertheless, it
      was observed an increase on anxyolitics benzodiazepine's utilization (3.8%;72.66
      DHD), although hypnotics benzodiazepine's suffered a marked decrease (
      21.9%;13.15 DHD). The expenditure has not followed the utilization's trend, and
      in the period in study the retail sale price expenditure increased 12%.
      Anxyolitic benzodiazepine's utilization accounted for 85% of the growth on
      expenditure observed in this study. At national level there were some asymmetries
      either on utilization's level or on drug utilization's pattern. In 2003, Faro,
      Braganca and Viana do Castelo were the sub-regions with the lowest utilization
      level and Portalegre and Evora the ones with the highest levels. Lisbon presented
      the highest decrease either on percentual (-13.8%) or on absolute (-13.45 DHD)
      values. DISCUSSION: Benzodiazepine's utilization in Portugal was considered of
      concern by International Narcotics Control Board. Therefore the stabilization on
      utilization, with even a small decrease, should be considered potentially
      positive. The asymmetries either on utilization's level or on drug utilization's
      pattern do not seem to be totally attributable to age-structure, unemployment
      levels or the percentage of retired people, as there wasn't a statistical
      significant relation between these variables. For this reason the variations on
      Benzodiazepine's utilization in Portugal seem to be attributed to a combination
      of different factors, which emphasize the need of more initiatives conducted to
      health care professionals and patients, in order to diminish the chronic use of
      these drugs.

PMID- 17234087
TI  - [Obesity and quality of life].
AB  - Obesity is considered one of the most relevant health problems of modern
      societies, as it constitutes a predominant risk factor in the development of
      various other diseases. The negative impact of obesity on the quality of life of
      individuals has been the subject of diverse research. The results of a test
      carried out at Gothenburg University in Sweden suggest that severe obesity is a
      debilitating factor both for health and psychosocial functioning. Research
      carried out in Madrid permitted identification of a profile of obese patients
      with impaired quality of life, which has enabled prophylactic intervention or
      early treatment of these cases to be considered. The results of a study carried
      out in the USA propose that pain would appear to be directly related with quality
      of life and could be considered a covariant of obesity, and should therefore be
      taken into account in obesity treatments. A study carried out in Oxford concluded
      that obese subjects or subjects with another chronic disease presented a
      deterioration in physical wellbeing, however only subjects with another chronic
      disease (without associated obesity) presented a deterioration in psychological
      wellbeing. The majority of studies suggest the negative influence of obesity and
      overweight on health and psychosocial functioning, however it is not possible to
      clearly define a linear relation between obesity and diminished quality of life.

PMID- 17234088
TI  - [Adipose tissue and adipokines].
AB  - Adipose tissue is an organ with an endocrine function among others. Adipokines
      there produced have several roles and can be, according to their main function,
      grouped in our groups: immunologic, cardiovascular, metabolic and endocrine
      adipokines. Interleukin-6, tumour necrosis factor a and complement factors B, C3
      and D (adipsin) and are within the first group. Adipsin was the one of the first
      adipokines identified. Ali this molecules have well defined roles in
      inflammation. It is well known the association between obesity and cardiovascular
      risk, which is demonstrated by the improvement of cardiovascular risk factors
      associated with weight loss. Among the adipokines with cardiovascular main
      function the renin--angiotensin axis molecules and plasminogen activator
      inhibitor--I will be highlighted. Metabolic function is attributed to molecules
      taught to have a role in energy homeostasis. Adipose tissue is mainly involved in
      lipid and glucose metabolism. Free fatty acids, adiponectin, resistin, agouti
      related peptide and visfatin are molecules involved in those metabolic pathways.
      Leptin is the paradigm of the adipose tissue endocrine function. It is almost
      exclusively produced by the adipocyte and it has a central role in energy storage
      regulation and fertility. Steroid inter-conversion also occurs in adipose tissue.
      Although knowledge regarding these molecules, their function and relations with
      other systems has increased lately; more studies are necessary in order to
      clarify mechanisms and clinical applications. Only that way it will be possible
      to effectively correct the obesity associated metabolic dysfunction and decrease
      the morbidity and mortality obesity related.

PMID- 17234091
TI  - [Rehabilitation of severe traumatic brain injury].

PMID- 17234089
TI  - [Role of the cerebellum in cognitive and behavioural control: scientific basis
      and investigation models].
AB  - Although classically considered to be involved only in motor coordination, the
      cerebellum has more recently been implicated also in cognitive control.
      Anatomical studies have shown the cerebellum to be linked to pre-frontal,
      occipito-parietal and temporal cortical associative areas, as well as to the
      limbic system, in a closed loop circuit. Functional studies revealed activation
      of the cerebellum during performance on cognitive tasks not related to movement.
      Pathological, morphological and functional imaging studies have shown the
      cerebellum to be one of the cerebral structures affected in some of the cognitive
      and behavioural developmental disorders, like Attention Deficit with
      Hyperactivity Disorder, Autism and Schizophrenia. Neuropsychological studies in
      patients with degenerative cerebellar ataxia also showed cognitive dysfunction,
      mainly of the executive type. Investigation performed with child and adult
      patients with focal lesions of the cerebellum has helped to better discriminate
      the cognitive role of specific areas on the cerebellum, revealing a
      characteristic constellation of cognitive deficits, affecting executive, visual
      spatial, linguistic and behavioural functions. However, much remains to be
      explained on the precise nature of cerebellar contributions to cognition, in part
      because of the difficulty in finding adequate investigation models. Studies
      performed on primates have contributed to better delineate the connections
      between the cerebellum and cortical cognitive domains, but is always uncertain to
      transfer this kind of data to the human brain. Functional imaging studies
      although useful to investigate directly in the human model and in real time, are
      not yet able to completely isolate cerebellar cognitive and behavioural
      functions. Degenerative and developmental disorders are not the most adequate
      model for studying cerebellar influence on higher mental functions, as they
      affect other regions besides the cerebellum. Young patients with isolated
      cerebellar stroke provide a useful clinical model for investigating cerebellar
      cognitive functions, because they permit to isolate in space and time the
      specific contribution of the cerebellum to the cognitive deficits.

PMID- 17234092
TI  - [Epidemiology and treatment of head injuries in Denmark 1994-2002, illustrated
      with hospital statistics].
AB  - INTRODUCTION: The purpose of this study was to illuminate the trends in the
      numbers of hospitalized head-injured patients in Denmark from 1994 to 2002
      compared to the preceding decade, and to comment on the response to
      recommendations from the National Board of Health concerning hospital treatment.
      MATERIALS AND METHODS: The National Patient Registry and the national register of
      causes of death were searched for ICD10 diagnoses corresponding to structural
      brain injury, selected cranial fracture diagnoses, and concussion as a first or
      secondary diagnosis. RESULTS AND CONCLUSION: The most important tendencies were
      an increasing number of intracranial haemorrhages and a decrease in the numbers
      of other structural brain injuries, cranial fractures and brain concussions. Age
      at injury and the ratio of males to females increased for all categories. The
      death rate in hospital was a constant 16.5% for intracranial haemorrhages but
      decreased for other structural brain injuries, from 19.3% in 1994 to 15.3% in
      2002. The number of hospitalizations of more than three months' duration
      increased correspondingly. In all, deaths in hospital decreased from 5.3 to 5.0
      per 100,000 population. Two centres for rehabilitation of the most severely
      injured 16% were established during the study period. The increasing number of
      hospitalizations of duration exceeding three months, but where the inclusion
      criteria for these centres were not fulfilled, emphasizes the need for follow-up
      of recommendations concerning county/regional hospital-based rehabilitation units
      for patients with moderate to severe head injury. In addition, better
      organization and coordination of follow-up of patients with sequelae after
      concussion are desirable.

PMID- 17234093
TI  - [Epidemiology of non-traumatic brain injury of sudden onset in Denmark 1994
      2002].
AB  - The purpose of this study was to illuminate trends in the incidence and duration
      of hospital courses in Denmark in 1994-2002 for patients with non-traumatic brain
      injury of sudden onset, due to spontaneous subarachnoid haemorrhage, revival
      after cardiac arrest, near-drowning, near-suffocation or electric shock and to
      compare to corresponding data from a contemporary investigation of head injuries.
      MATERIALS AND METHODS: The national hospital register was searched for hospital
      courses starting between 1 January 1994 and 31 December 2002, including
      rehabilitation and corresponding to ICD10 diagnoses covering the above-mentioned
      causes of non-traumatic brain injuries. RESULTS AND CONCLUSION: After direct age
      standardization to the European Standard population, the incidence of hospital
      courses after SAH decreased slightly to 12.3 per 100,000 of the population in
      2002. Mean age at injury increased by 3.6 years to 56.2. In particular for men,
      the maximum age-specific incidence increased considerably. Hospital lethality
      increased slightly to 29.2%. The age-standardized incidence of hospital courses
      after revival following cardiac arrest increased from 3.37 in 1994 to 4.49 per
      100,000 in 2002. During the same period, hospital lethality decreased from 42.9%
      to 34.0%, and the number of courses of long duration increased correspondingly.
      All in all, bed occupancy beyond 3 months after SAH and cardiac arrest was half
      of the occupancy after traumatic injuries. A number of other less numerous causes
      of non-trauma-tic brain injury should also be taken into consideration. For equal
      treatment and rehabilitation of patients with hospital courses beyond three
      months, the number of hospital beds should be the same for traumatic and non
      traumatic brain injuries.

PMID- 17234094
TI  - [Traumatic brain injury--pathophysiology and clinic seen from a neurosurgical
      point of view].
AB  - Traumatic brain injury (TBI) can be divided into primary and secondary brain
      damage. The primary damage occurs at the time of impact, induces neuronal death
      and is refractory to treatment. The secondary damage occurs at some time after
      the impact, has extracranial (hypoxia/hypotension) and intracranial
      (haematomas/swelling) causes and is largely preventable and treatable. Initially,
      TBI should be treated by the principles of ATLS. Space-occupying haematomas
      should be evacuated and neuro-intensive monitoring and treatment of intracranial
      pathology are mandatory in severe TBI.

PMID- 17234095
TI  - [Pituitary insufficiency following head trauma].
AB  - Brain injury following head trauma is a potential cause of acquired
      hypopituitarism, although regarded as uncommon. Consequently, such patients do
      not routinely undergo neuroendocrine evaluation. Recent data suggest
      hypopituitarism to be more common than previously stated, with a prevalence of at
      least 25% in long-term survivors. As untreated hypopituitarism is likely to delay
      recovery and rehabilitation, this calls for a change in the current management of
      patients suffering traumatic brain injury. In this article, we will review
      current knowledge in this field.

PMID- 17234096
TI  - [Magnetic resonance imaging in severe traumatic brain injury].
AB  - Modern neuroimaging techniques are continuously improving the diagnostic and
      prognostic assessment of patients with traumatic brain injury. The rapid
      developments within the field of magnetic resonance imaging (MRI) in particular
      provide several complementary tools for evaluating structural and functional
      changes in the injured brain. This article summarizes the current clinical use
      and future potential of the main structural and functional MRI techniques in the
      evaluation of severe non-missile head injury in the subacute phase.

PMID- 17234097
TI  - [Cognitive disturbances following severe traumatic brain injury].
AB  - Traumatic brain injury (TBI) very often has extensive effects of cognitive
      character such as changes in recognition, thought, memory, language and
      perception. The purpose of this paper is to give a short status of cognitive
      impairment after severe traumatic brain injury and to illustrate that cognitive
      impairment varies according to levels of consciousness. The article shortly
      describes typical observed behaviour in the patient when waking up after severe
      TBI, including post-traumatic amnesia.

PMID- 17234098
TI  - [Dysphagia--an overlooked problem in neurorehabilitation].
AB  - INTRODUCTION: The purpose of this study was to evaluate the management of
      dysphagia in patients with traumatic brain injury (TBI) and adjoining disorders
      during multidisciplinary neurorehabilitation in phase I and II in Denmark and
      abroad. MATERIALS AND METHODS: The study was conducted as structured interviews
      at six outstanding international neurorehabilitation institutions and as a
      national questionnaire survey including five phase I neurointensive wards and two
      phase II neurorehabilitation institutions. RESULTS: Data from the study visits
      showed that the international clinics received patients with cuffed tracheostomy
      tubes, had 24-hour medical support, and semiintensive monitoring. Patients were
      treated by multidisciplinary teams and all were clinically and instrumentally
      examined for dysphagia. Data from the Danish questionnaire survey showed that the
      two neurorehabilitation institutions did not receive patients with cuffed
      tracheostomy tubes. Both institutions had 24-hour medical support,
      multidisciplinary teams and monitoring of saturation. Clinical and instrumental
      examinations of dysphagia were not systematic procedures in either phase I or II.
      CONCLUSION: The study demonstrates the need for clinical guidelines on the
      examination and treatment of dysphagia in patients with TBI and adjoining
      disorders within neurorehabilitation in phase I and II in Denmark. There is also
      a need to clarify the management of dysphagia in patients with cuffed
      tracheostomy tubes.

PMID- 17234099
TI  - [Subacute intensive rehabilitation after severe traumatic brain injury. Follow-up
      6 months after discharge].
AB  - INTRODUCTION: In September 2000 the Brain Injury Unit at Hvidovre Hospital was
      established, offering subacute intensive rehabilitation to patients with severe
      traumatic brain injury. Uptake area: Eastern part of Denmark, the Faroe Islands
      and Greenland. Outcome 6 months after discharge is presented for patients from
      the first 2 years, focusing on disability and social factors. MATERIALS AND
      METHODS: Patients were selected on the basis of the Glasgow Coma Scale after end
      of sedation to ensure that the most severely-injured were included in the study.
      Rehabilitation was initiated immediately regardless of the level of
      consciousness. Patients were assessed using established rating-scales. Local
      social authorities were involved at discharge. RESULTS: Of 77 consecutive
      patients, 5 died before follow-up and 6 patients were not seen at follow up. 79%
      of the remaining group had post-traumatic amnesia lasting more than 4 weeks.
      Nonetheless, 4 out of 5 were able to walk independently, 79% were living at home
      under normal conditions and 76% were independent on a personal level. A majority
      suffered from cognitive dysfunctions, which was often the major remaining
      disability. 20% had resumed normal work or education. CONCLUSION: The
      centralisation of rehabilitation in Denmark after very severe brain damage made
      it possible to conduct a structured plan for treatment and assessment during
      subacute rehabilitation and 6 months after discharge of patients with very severe
      traumatic brain injury. This has demonstrated that rehabilitation of even the
      most severely brain-damaged patients can be valuable.

PMID- 17234100
TI  - [Housing and work outcomes one year after severe brain injury. An interview-based
      follow-up study].
AB  - INTRODUCTION: Housing and employment after severe brain injury can be applied as
      an estimation of functional outcome. Using these parameters we studied a Danish
      population who received intensive neurorehabilitation one year after brain
      injury. MATERIALS AND METHODS: All patients admitted to the Neurorehabilitation
      Centre in Western Denmark for severe brain injury during the period 1st July 02
      31st December 03 were asked to participate in a follow-up study. Out of 165
      patients, 153 accepted participation. Aetiologies were traumatic brain injury
      (TBI) (63), subarachnoid haemorrhage (42), stroke (25) and other disorders (23).
      Housing and employment were categorized after interviews at follow-up. Following
      logistic regression analysis determinants for independent housing were studied.
      RESULTS: Approximately 5% were back at work or continued their education and 31%
      were still on sick leave. 52% lived independently. Short admittance in the
      primary ward and a high functional level at the start of rehabilitation were
      associated with independent living. Patients with brain injury due to mixed
      aetiologies, including anoxic or metabolic disturbances, showed impaired
      capability of independent living compared to patients with TBI. Age was not
      associated with housing. CONCLUSION: Return to work is not a realistic goal for
      rehabilitation one year after severe brain injury, whereas living independently
      can be achieved by approximately half of the patients. The condition, however,
      seems complex and in several cases appears dependent on support from relatives
      and other caretakers.

PMID- 17234101
TI  - [Fatal bicycle accidents involving right turning heavy goods vehicles--forensic
      pathological findings].
AB  - INTRODUCTION: The objective of this study was to describe the forensic
      pathological findings in autopsies of cyclists involved in fatal accidents with
      right-turning, heavy goods vehicles (HGV). DESIGN AND SETTINGS: Retrospective
      analysis based on medico-legal autopsy reports concerning persons involved in
      fatal traffic accidents in Denmark between 1996 and 2005. Cyclists and moped
      riders hit by a right-turning HGV were included. Forensic pathological findings,
      blood alcohol levels, place of death as well as several traffic parameters were
      registered. RESULTS: Twenty-five autopsies were included. In 20 cases (80%),
      death had occurred instantly. Also in 20 cases (80%), injuries in at least three
      body regions were found at autopsy. There were no cases with injuries in only one
      body region. There were fewest cases with head/neck injuries. In 16 cases,
      injuries in one or more body regions were so severe as to be described as
      complete crushing (conquassatio). CONCLUSION: In traffic accidents involving
      cyclists and right-turning HGVs, the cyclist is more often run-over rather than
      merely hit by the HGV. This mechanism of injury is crucial for both the severity
      and the distribution of injuries. This is reflected in this study by the number
      of multiple body regions involved, the number of complete crushing injuries and
      by the number of cases where death had occurred instantly. Future efforts should
      focus on the prevention of these accidents.

PMID- 17234102
TI  - [Postoperative tetraplegia as a result of positioning].
AB  - Tetraplegia is a rare complication of positioning. A 36-year-old healthy man with
      a BMI of 40 underwent a sigmoidostomy reversal under general anaesthesia in the
      Trendelenburg position. Post-operatively the patient experienced pain with
      dysaestesia and weakness of both legs and arms. A medullary cervical compression
      was suspected, and prednisolone medication was initiated. An MRI showed no signs
      of either cervical discus prolaps or cervical stenosis. Myelography was not
      performed. The patient recovered well. Perioperative positioning was most likely
      the explanation of this condition.

PMID- 17234103
TI  - [Spontaneous occlusion of a pseudoaneurysm in a thyroid cyst].
AB  - A case of pseudoaneurysm formed in a thyroid cyst diagnosed by Doppler sonography
      is presented. Its genesis was regarded as idiopatic, and the condition resolved
      spontaneously less than four weeks after the initial diagnosis.

PMID- 17234104
TI  - Canadian consensus statement on the use of intravenous immunoglobulin therapy in
      dermatology.
AB  - BACKGROUND: As a safe, well-tolerated, and potentially beneficial therapy,
      intravenous immunoglobulin (IVIG) has been increasingly used by dermatologists to
      treat immune-mediated skin disease. However, practical and comprehensive
      guidelines for the use of IVIG have yet to be established. OBJECTIVE: To develop
      the first Canadian consensus statement on the use of IVIG therapy in skin
      disease. METHODS: A group of Canadian dermatologists convened to discuss current
      issues in IVIG therapy. The participants reviewed and evaluated the literature
      and shared clinical experience. Using a modified Delphi process, a consensus
      statement was developed. RESULTS: Herein we provide a brief overview of pemphigus
      vulgaris, pemphigus foliaceus, bullous pemphigoid, mucous membrane pemphigoid,
      epidermolysis bullosa acquisita, Stevens-Johnson syndrome, and toxic epidermal
      necrolysis. Recommendations for the management of these diseases are detailed,
      and therapeutic algorithms for the treatment of various autoimmune mucocutaneous
      blistering diseases are presented. The appropriate use of IVIG therapy is placed
      in context for each disease. CONCLUSION: Although preliminary data suggest that
      IVIG is a safe and effective therapy for many skin disorders, uncontrolled
      clinical trials, case series, and anecdotal case reports dominate the literature.
      Collaborative randomized controlled trials are required to firmly establish the
      role of IVIG in dermatology.

PMID- 17234105
TI  - Effect of intravenous immunoglobulin on prednisone dose in patients with
      pemphigus vulgaris.
AB  - BACKGROUND: Current therapeutic options for the treatment of pemphigus vulgaris
      (PV) are prednisone and immunosuppressants. Patients unresponsive to high-dose
      systemic corticosteroids and conventional immunosuppressants may respond to
      intravenous immunoglobulin (IVIG). OBJECTIVE: The primary outcome was the change
      in prednisone dose at 6 months and 1 year post-IVIG administration. METHODS: A
      retrospective chart review of PV patients treated at Sunnybrook and Women's
      College Health Sciences Centre between January 1999 and October 2004 was
      conducted. Demographic information, corticosteroid and IVIG use, dosage, and the
      timing of administration for all patients were obtained. RESULTS: Eight PV
      patients, mean age of 50 years (+/- 14.7 years), were reviewed. There was a
      significant decrease in mean prednisone dose at 6 months (45%) and 12 months
      (71%) compared with the mean dose at the start of treatment (p < .05).
      LIMITATIONS: Concomitant medication use may influence results. CONCLUSION: This
      study demonstrates that IVIG can lower prednisone doses in PV patients.

PMID- 17234106
TI  - Treatment of mycosis fungoides: overview.
AB  - BACKGROUND: Mycosis fungoides (MF) is the most common clinicopathologic subtype
      of primary cutaneous T-cell lymphoma. OBJECTIVE: The therapy of MF is highlighted
      in this overview. RESULTS AND CONCLUSIONS: Skin-directed MF therapies include
      topical corticosteroids, nitrogen mustard, carmustine (BCNU), topical bexarotene
      gel, imiquimod cream, radiotherapy, total skin electron beam therapy, and
      phototherapy. Systemic therapies include extracorporeal photopheresis,
      interferon, oral bexarotene, denileukin diftitox, monoclonal antibodies and
      cytokine therapy, and other systemic chemotherapy. Finally, some investigative
      therapeutic modalities are presented.

PMID- 17234107
TI  - Are narrow-band ultraviolet B home units a viable option for continuous or
      maintenance therapy of photoresponsive diseases?
AB  - BACKGROUND: Phototherapy is an effective treatment for several photoresponsive
      diseases. Many patients are unable to attend hospital-based treatment and prefer
      home phototherapy. OBJECTIVES: The purpose of this study is to survey patients
      who were prescribed home phototherapy to determine the viability of narrow-band
      ultraviolet B home units in the continuous or maintenance treatment of
      photoresponsive diseases. METHODS: A patient questionnaire was prepared focusing
      on different areas of interest: the reason for choosing home therapy, appropriate
      teaching, previous medical treatment, present exposure therapy, improvement of
      the condition, side effects, regular dermatologic follow-ups, and the
      effectiveness of this approach. Twenty-seven patients who attended the
      photodermatology clinics at the Sisters of Charity of Ottawa Health Service at
      the Elisabeth Bruyere Health Centre in Ottawa and the Ottawa Hospital Civic
      Campus were contacted, and they completed a questionnaire by telephone or
      electronic mail. RESULTS: Twenty-five patients completed the questionnaire. One
      refused to participate, and one was out of the country. The main reasons for
      choosing home phototherapy were time (40%), travel expenses (25%), difficulty
      with work schedule (17%), and recommendation by a physician (6%). Other reasons
      included loss of earnings, personal stress, knowledge that the disease recurs
      when phototherapy is discontinued, moving from the city, personal stress, and the
      convenience of being at home. Regarding the effectiveness of the home
      phototherapy, 24 patients (96%) viewed the home unit approach to be effective.
      All patients agreed that they would continue the treatment; they would repeat it,
      and they would recommend it. Few patients reported side effects, such as erythema
      (36%), blisters (1%), pruritus (8%), and dryness (1%). Fourteen patients (56%)
      reported not experiencing any side effects. CONCLUSION: Narrow-band ultraviolet B
      home phototherapy was found to be an effective form of maintenance therapy for
      photoresponsive diseases. It is safe and presents few side effects when patients
      receive appropriate guidelines, teaching, and follow-ups.

PMID- 17234108
TI  - XP-828l in the treatment of mild to moderate psoriasis: randomized, double-blind,
      placebo-controlled study.
AB  - BACKGROUND: XP-828L, a protein extract obtained from sweet whey, has demonstrated
      potential benefit for the treatment of mild to moderate psoriasis in an open
      label study. OBJECTIVE: To study in a randomized, double-blind, placebo
      controlled study the safety and efficacy of XP-828L in the treatment of mild to
      moderate psoriasis. DESIGN: XP-828L 5 g/d (group A, n = 42) or placebo (group B,
      n = 42) was given orally for 56 days followed by XP-828L 5 g/d in group A and by
      XP-828L 10 g/d in group B for an additional 56 days. RESULTS: Patients receiving
      XP-828L 5 g/d for 56 days had an improved Physician's Global Assessment (PGA)
      score compared with patients under placebo (p < .05). Considering the data of
      group A only, the PGA score improved from day 1 to day 56 (p < .01); the
      Psoriasis Area and Severity Index score improved as well, but to a lesser extent
      (p < .05). CONCLUSION: Oral administration of 5 g/d XP-828L compared with a
      placebo significantly improved the PGA score of patients with mild to moderate
      psoriasis.

PMID- 17234109
TI  - Management and dermoscopy of fast-growing nevi in pregnancy: case report and
      literature review.
AB  - BACKGROUND: The relationship between pregnancy and a change in melanocytic nevi
      is still controversial. Moreover, management of the rapid evolution of a nevus in
      an unauspicious melanocytic lesion can be a clinical challenge in pregnancy.
      METHODS: This article examines a case of a fast-growing deep penetrating nevus in
      a pregnant woman and provides a literature review of articles relative to
      pregnancy and nevi change, the management of fast-growing pigmented lesions, and
      the role and usefulness of dermoscopy in these cases. RESULTS: Recent studies
      have documented that pregnancy is not associated with any significant change in
      the size of melanocytic nevi. The management of fast-growing melanocytic lesions
      during this period compulsorily leans toward excision. Dermoscopy can be useful,
      providing clinicohistopathologic correlations and a better assignment of the
      lesion. CONCLUSION: This case report and review provide important management
      considerations for nevi during pregnancy. Early intervention with aggressive
      treatment measures is the best management for fast-growing lesions, and
      epiluminescence dermoscopy can assist the management, although still remaining a
      second-level examination, useful for documentation and for a better
      classification of the lesion.

PMID- 17234110
TI  - Primary systemic amyloidosis presenting as extensive cutaneous ulceration.
AB  - BACKGROUND: We report a case of primary systemic amyloidosis in a 78-year-old
      Caucasian woman presented as a nonhealing ulcer on the right thigh for 3 months.
      Histopathology of the skin revealed widely thickened walls of middermal and
      subcutaneous vessels from deposition of amorphous eosinophilic material that
      stained positively with Congo red and crystal violet. OBJECTIVE: This case
      represents a very unusual presentation of primary systemic amyloidosis, one in
      which the cutaneous manifestations provided the first signs of a devastatingly
      widespread multiorgan infiltration of amyloid protein. CONCLUSION: This
      presentation of the disease may signify an advanced stage with a grave prognosis
      as our patient passed away 3 months after development of the cutaneous
      ulceration.

PMID- 17234111
TI  - Extensive cranial infiltration by basal cell carcinoma.

PMID- 17234112
TI  - Lipolysis of lipomas in patients with familial multiple lipomatosis: an
      ultrasonography-controlled trial.
AB  - BACKGROUND: Surgery of multiple lipomas, as in patients with familial multiple
      lipomatosis, is often limited by poor aesthetic outcome owing to extensive
      scarring. For this reason, phosphatidylcholine (PDC) has been widely used to
      treat areas of localized fat accumulation. However, no reports of lipoma therapy
      with intralesional application of PDC, that is, injection lipolysis, have been
      published to date. OBJECTIVE: To investigate whether injection lipolysis with PDC
      is an effective therapeutic option for patients with multiple lipomas. METHODS:
      Thirty lipomas in 10 patients were sonographically measured prior to treatment.
      Four injections at intervals of 6 to 8 weeks were done. Sonographic measurements
      of lipoma size were repeated before each injection. Side effects, a pain score
      using a visual analogue scale, and patient satisfaction were noted. In one
      lipoma, histologic changes after lipolysis are described. RESULTS: After four
      injections, a significant reduction in size of 45.8% was achieved. No complete
      elimination was seen in any lipoma. Histology showed a mild granulomatous septal
      panniculitis. Hematoma occurred in eight cases (27%). Four patients described
      pain on pressure for 3 days after injection. No severe side effects or systemic
      reactions were observed. CONCLUSION: Although surgery is the gold standard for
      lipoma therapy, injection lipolysis with PDC can also significantly reduce lipoma
      size. Complete elimination was not observed in any lipoma. Given that this was a
      short-term study, long-lasting therapeutic effects and possible recurrence of
      lipoma cannot be evaluated.

PMID- 17234113
TI  - Reliability of dermatologists in acne lesion counts and global assessments.
AB  - BACKGROUND: There is a paucity of data on the reliability of dermatologists in
      acne lesion counting and global severity assessments. The effects of training and
      practice on reliability are also uncertain. The objective of this study was to
      determine the reliability of these outcome measurements when performed by trained
      dermatologists. METHODS: Eleven dermatologists were divided into two groups that
      evaluated the same six acne subjects twice on the same day. A training session
      was provided either after (group A) or before (group B) the first patient
      evaluation sessions. Reliability of raters in lesion counting and global severity
      assessment was determined by calculation of intraclass correlation coefficients
      (ICCs). ICC values close to 1.0 indicate excellent reliability, whereas values
      less than 0.75 are considered unacceptable. RESULTS: Intrarater ICCs ranged from
      0.37 to 0.99 for noninflammatory lesions, 0.26 to 0.97 for inflammatory lesions,
      and 0.56 to 0.83 for global assessments for group A (trained after);
      corresponding values for group B (trained before) were 0.84 to 0.98, 0.61 to
      0.95, and 0.43 to 0.91. ICC values >or= 0.75 for all three outcome parameters
      were observed in one of six group A and three of five group B raters. Interrater
      ICCs for groups A and B after the first evaluation session were 0.17 versus 0.68
      for noninflammatory counts, 0.84 versus 0.72 for inflammatory counts, and 0.71
      versus 0.65 for global assessments, respectively. Corresponding values after
      session 2 were 0.79 and 0.77 for noninflammatory, 0.81 and 0.90 for inflammatory,
      and 0.61 and 0.77 for global assessments. CONCLUSION: Dermatologists tended to be
      reliable in acne lesion counting but somewhat less so in global assessments.
      Training tended to improve group reliability in noninflammatory lesion counts and
      increased the proportion of raters with good reliability in all three outcome
      measures. Practice enhanced reliability in all outcome measurements.

PMID- 17234114
TI  - Outbreak of acupuncture-associated cutaneous Mycobacterium abscessus infections.
AB  - BACKGROUND: Cutaneous atypical mycobacterial infections have been increasingly
      described in association with cosmetic and alternative procedures. OBJECTIVE: We
      report an outbreak of acupuncture-associated mycobacteriosis. Between April and
      December 2002, 32 patients developed cutaneous mycobacteriosis after visiting an
      acupuncture practice in Toronto, Canada. RESULTS: Of 23 patients whose lesions
      were biopsied, 6 (26.1%) had culture-confirmed infection with Mycobacterium
      abscessus. These isolates were genetically indistinguishable by amplified
      fragment length polymorphism. The median incubation period was 1 month. Of 24
      patients for whom clinical information was available, 23 (95.8%) had resolution
      of their infection. All patients developed residual scarring or
      hyperpigmentation. CONCLUSION: Nontuberculous mycobacteria should be recognized
      as an emerging, but preventable, cause of acupuncture-associated infections.

PMID- 17234115
TI  - Predominant dermoscopic patterns observed among nevi.
AB  - BACKGROUND: It has been clinically observed that patients' "normal" moles
      resemble each other. Whether this concept is applicable to dermoscopic practice
      has not been sufficiently studied. OBJECTIVE: To investigate whether physicians
      evaluating dermoscopic images would identify common dermoscopic profiles of nevi
      within individual patients. METHODS: Images of 205 nevi belonging to 18 patients
      were evaluated by 2 dermatologists for dermoscopic global pattern, color, and
      specific structures. We defined dermoscopic patterns as dominant if seen in >or=
      40% of the patient's nevi; a minor pattern was defined as 20 to 39%. RESULTS: A
      dominant pattern was seen in 15 patients (83%). In 13 (72%) of the patients, >or=
      80% of the nevi were classified into one, two, or three global patterns. The
      reticular global pattern was the most prevalent dominant pattern, seen in 9
      patients (50%); the homogeneous pattern was the most prevalent minor pattern,
      seen in 16 patients (89%). CONCLUSION: Individuals tend to have one to three
      predominant dermoscopic nevus global patterns.

PMID- 17234116
TI  - Dermatologic signs.
AB  - BACKGROUND: Dermatology signs serve as important clues to primary skin disorders
      and internal conditions. OBJECTIVE AND METHODS: To highlight major cutaneous
      signs based on a MEDLINE literature search from 1966 to March 2006. RESULTS AND
      CONCLUSIONS: A multitude of signs exist in dermatology. Appreciation and
      knowledge of cutaneous signs will enhance the care of patients with dermatologic
      manifestations.

PMID- 17234117
TI  - Dermatologic treatment during pregnancy: practical overview.
AB  - BACKGROUND: This article provides a practical overview of dermatologic medication
      use in pregnancy. OBJECTIVE: The therapeutics of the following common dermatoses
      are reviewed: acne, psoriasis, and bacterial, fungal, viral, and parasitic
      infections. Antipruritic, analgesic, and topical anesthetic use in pregnancy is
      reviewed as well. CONCLUSIONS: At the end, the reader is challenged with a series
      of applied clinical scenarios that highlight the presented material and provide
      information on additional important medications.

PMID- 17234118
TI  - Bilateral extensive periorbital milia en plaque treated with electrodesiccation.
AB  - BACKGROUND: Milia en plaque (MEP) is a rare form of milia. Only 25 cases of this
      rare condition have been reported to date (MEDLINE search). Only one previous
      case of MEP has been treated with electrodesiccation. OBJECTIVE: To report a new
      case of this rare condition and present the outcome with electrodesiccation.
      CONCLUSION: The case is being reported here to highlight the features of this
      rare but now well-recognized dermatologic condition, which has been reported
      increasingly in the recent past, to discuss the various treatments tried, and to
      share our experience of treating patients with the simple, inexpensive, easily
      available, and nonsophisticated office procedure of electrodesiccation.

PMID- 17234119
TI  - Perianal Paget's disease.
AB  - BACKGROUND: Perianal Paget's disease is an uncommon intraepithelial neoplasm that
      involves areas affluent with apocrine glands, most frequently in the female
      external genitalia, but may also affect the perianal region. OBJECTIVE: We
      present the pathologic and clinical management of a case of Paget's disease
      involving the perianal region, in which diagnosis was delayed for 8 years.
      CONCLUSIONS: The importance of a high index of suspicion for early diagnosis is
      emphasized, which should be followed by aggressive surgical treatment with wide
      excision and local reconstruction.

PMID- 17234120
TI  - Imiquimod 5% cream use for the treatment of basal cell carcinomas in elderly
      patients, in long-term care facilities, not amenable to surgical or radiation
      therapy.

PMID- 17234121
TI  - Editor's Note.

PMID- 17234122
TI  - Toward a modern concept of sepsis: new answers to ancient questions.
AB  - It is commonly thought that bacterial endotoxin such as lipopolysaccharide (LPS)
      causes sepsis. Authors argue that LPS is merely a disease marker. The real
      mechanism of sepsis lies in the Toll-like receptors that suppress sepsis caused
      by tissue injury or endotoxin. When Toll-like receptors' initial suppression role
      is overwhelmed, sepsis ensues.

PMID- 17234123
TI  - Defeating drug resistance in cancer.
AB  - Multiple resistance to cytotoxic cancer drugs dramatically reduces the
      effectiveness of these drugs on many occasions. ABC (ATP-binding cassette)
      transporters pump out cytotoxic cancer drugs from cells, preventing them from
      reaching therapeutic levels. However, co-administration ABC transporter
      inhibitors with cytotoxic cancer drugs did not effectively improve the treatment
      outcome. The mechanisms and remedies are discussed.

PMID- 17234124
TI  - The causation of childhood leukemia: a paradox of progress?
AB  - Treatments, mostly combination chemotherapies, have been remarkably effective in
      managing many childhood leukemia cases. However, childhood leukemia is a
      heterogeneous (mixed) disease originating from different cell lineages and with
      distinct mechanisms. Authors described hypotheses of "population mixing" and
      "delayed infection" as causes of childhood leukemia.

PMID- 17234125
TI  - Vaccination against prion diseases.
AB  - Prion diseases are a group of fatal neurodegenerative conditions that affect
      humans and a wide variety of animals. To date there is no therapeutic or
      prophylactic approach against prion diseases available. The causative infectious
      agent is the prion, also termed PrP(Sc), which is a pathological conformer of the
      cellular prion protein PrP(C). As passive immunization studies with PrP(C)
      specific antibodies indicated that immunotherapeutic strategies can prevent prion
      replication, researchers are now aiming at the development of active prion
      vaccines.

PMID- 17234126
TI  - Treatment and prevention of enteric infections with toxin-binding probiotics.
AB  - Nearly all antibiotics aim at killing the bacteria, which eventually develop
      antibiotic resistance under "survival pressure." The pathology exerted by many
      pathologic bacteria is through secreting toxins. Probiotics, either harmless live
      bacteria or dead ones, can be molecularly engineered to express receptors for the
      toxins and absorb and eliminate them from binding to their natural receptors,
      thus reducing or eliminating the pathological impact of bacterial infection.

PMID- 17234127
TI  - Genetic progress towards the molecular basis of common autoimmunity.
AB  - Identification of the genetic determinants that underlie autoimmune diseases
      implicates new biochemical pathways in disease pathogenesis. The authors describe
      how recent advances in genetic knowledge of autoimmunity have pointed to aberrant
      negative regulation of autoreactive T-cells as a key step in autoimmunity. The
      tissue specificity of autoimmune attack is also under genetic control and
      variations in tissue-specific factors also appear to have a role.

PMID- 17234128
TI  - Global systems biology and personalized healthcare solutions.
AB  - Most drugs don't work optimally in most patients. The same drug can exert a
      significant overall therapeutic benefit in some patients while post a pronounced
      overall toxicity risk in others with the same disease. Pharmacogenomics has
      progressively received attention in the drug development process. But genetics is
      not the only factor that contributes to the differences that individual patients
      respond to drugs. Enter global systems biology.

PMID- 17234129
TI  - Genetic tools to tailor cancer prevention by NSAIDs.
AB  - It was shown that NSAIDs, such as aspirin or Celebrex, are effective cancer
      preventive agents when taken regularly. However, the long-term use of NSAIDs, the
      cyclooxygenase (COX) inhibitors, may have significant adverse effects - primarily
      on the gastrointestinal (inhibiting COX-1) and cardiovascular (inhibiting COX-2)
      systems. Genetic analysis of enzymes (including COX) involved in the
      prostaglandin synthesis should reveal and predict a person's benefits vs.
      toxicity resulting from the NSAID treatment.

PMID- 17234130
TI  - Putting fat cells onto the road map to novel therapeutic strategies.
AB  - Fat cells are traditionally considered dormant cells, quietly functioning in
      lipid accumulation and lipolysis. In recent years, fat cells received a glowing
      appraisal and were found to be an important player in energy homeostasis,
      tumorigenesis, immunity, and reproduction, via their endocrine and regulatory
      functions. Fat cells secrete adipokines, many of which are inflammation-related
      peptides such as cytokines and cytokine-like molecules.

PMID- 17234131
TI  - Battle for survival: interplay between pathogenic mycobacteria and the host
      immune system.
AB  - Mycobacteria tuberculosis infects about one third of the world population in
      their life times and causes millions of deaths each year. M. tuberculosis has a
      unique capability to circumvent the bactericidal activities of macrophages - the
      frontline defenders of the host immunity. New understanding of this mechanism has
      positioned scientists to develop therapies that allow host immune system to gain
      an upper hand.

PMID- 17234132
TI  - Turning "waste" into gold: identification of novel stem cells from human
      umbilical cord blood.
AB  - Due to ethical concerns, human embryonic stem cells have limited availability and
      practical usefulness. Adult stem cells are present within tissues of adult
      organisms and are responsible for cell turnover or repopulation of tissues under
      normal or exceptional circumstances. Multi-potent stem cells have been isolated
      from the umbilical cord blood and they offer promising therapeutic potentials.

PMID- 17234133
TI  - Molecular Trojan horses for blood-brain barrier drug delivery.
AB  - Molecular Trojan horses are genetically engineered proteins that cross the blood
      brain barrier (BBB) via endogenous receptor-mediated transport processes.
      Molecular Trojan horses provide a brain drug targeting technology that allows for
      the non-invasive delivery of large molecule therapeutics to the human brain. The
      development of BBB drug targeting technology is an arcane area of discovery
      medicine that suffers from chronic under-development.

PMID- 17234134
TI  - Adult neurogenesis as a potential therapy for neurodegenerative diseases.
AB  - Neurodegenerative diseases, such as Huntington's disease, Parkinson's disease,
      Alzheimer's disease, and amyotrophic lateral sclerosis (ALS), are progressive
      neurological diseases that affect millions of people worldwide. Recent
      identification and advances in our understanding of multi-potent neural stem
      cells/progenitors in the mature CNS has raised the possibility that these
      discoveries can be translated into an effective therapy for degenerative
      neurological disease.

PMID- 17234135
TI  - Defining correlates of T cell protection against infection.
AB  - It has been known for a long time that memory CD8+ T cells are the main players
      in conferring long-lasting and effective protection against infection with
      intracellular pathogens. The generation of instantly protective memory cells, so
      called effector memory T cells, represents the basic principle of T cell-based
      vaccination strategies. Therefore, the understanding of the exact mechanisms
      required for in vivo generation of distinct CD8+ memory T cell subtypes will
      become the crucial rationale for enhancing the efficiency and quality of vaccine
      induced protective immunity.

PMID- 17234136
TI  - Gene therapy for clinical transplantation: where do we stand in 2006?
AB  - Gene therapy holds a great promise to prevent allograft rejection or to induce
      transplant tolerance. Many achievements in vector development have allowed the
      progression of this therapy to become more attainable in clinical
      transplantation. In this articles, the authors examine the exciting development
      in various vector technologies that allows this form of therapy to take the
      central stage of clinical transplantation. Also highlighted are various
      therapeutic strategies that might ultimately result in the realization of gene
      based treatment in clinical transplantation.

PMID- 17234137
TI  - Role of nanotechnology in HIV/AIDS treatment: potential to overcome the viral
      reservoir challenge.
AB  - Insufficient concentrations and very short residence time of the anti-retroviral
      agents at the cellular and anatomical sites are among major factors that
      contribute to the failure of eradicating HIV from reservoirs and the development
      of multidrug resistance against antiretroviral agents. In recent years,
      nanotechnology-based drug delivery systems have shown remarkable ability to
      overcome many of the same anatomical and physiological barriers and deliver the
      therapeutic agents locally at the site of systemic diseases such as cancer.

PMID- 17234138
TI  - The impact of preventive HPV vaccination.
AB  - The clearly defined causation by papillomavirus (HPV) and precursor lesions of
      cervical cancer have made this cancer largely preventable through Pap screening
      programs, and now by vaccination with Gardasil. This represents an important
      public health success story and here the authors summarize the potential impact
      of preventive HPV vaccination and some of the outstanding questions.

PMID- 17234139
TI  - The genetic and environmental basis of hepatocellular carcinoma.
AB  - Liver cancer is among the most common malignancies, impacting significantly
      across all societies worldwide. The lethal impact of this prevalent cancer is
      unlikely to change considerably in the near future due to a limited understanding
      of disease pathogenesis on the molecular, cellular, and environmental levels and
      how current knowledge might be converted into new preventive, therapeutic and
      diagnostic approaches. This article highlights the current challenges and
      opportunities in this critical area of unmet need.

PMID- 17234140
TI  - Improving anti-HCV therapy.
AB  - Hepatitis C virus (HCV) infects about 2% of the world population or approximately
      123 million people. The disease causes a significant level of morbidity and
      mortality among those afflicted. The combination of interferon and ribavirin is
      effective in many patients. However, the right treatment doses and duration,
      among other attributes, have a large impact on the treatment outcome.

PMID- 17234141
TI  - "Dressed-up" naked plasmids: emerging vectors for non-viral gene therapy.
AB  - The non-viral vectors and targeting methods offer some specific advantages. These
      include better safety profiles (lower toxicity and non-infectious properties) and
      the capacity to transfer large genes and low production costs. The clinical
      usefulness of non-viral methods has been hindered by their relatively low gene
      delivery and transgene expression efficiencies. However, recent problems in
      clinical trials using viral vectors renewed interest in non-viral technologies,
      particularly that the properties of non-viral vectors make them appear closer to
      the traditional pharmaceutics.

PMID- 17234142
TI  - Gene therapy for hemophilia A.
AB  - Hemophilia A is an X-linked bleeding disorder caused by defective coagulation
      Factor VIII (FVIII). Although the efficacies of existing treatment using purified
      or recombinant FVIII are good, there remain shortcomings in using this particular
      form of treatment. A few FVIII gene therapy clinical trials have been initiated
      with modest improvements recorded, but these are no longer being continued due to
      insufficient efficacy. However, with the progress in the development of gene
      delivery vectors and the availability of mouse and canine hemophilia A models,
      gene therapy of hemophilia A remains an area of hot pursuit.

PMID- 17234144
TI  - DNA vaccines: recent technological and clinical advances.
AB  - DNA vaccines generate both T cell and B cell (or antibody) mediated immunities.
      Methods such as prime-boost regimens and the use of adjuvants in combination with
      the DNA vaccine have enhanced the therapeutic effectiveness of DNA vaccines in
      the treatment of cancer, infectious diseases, autoimmune diseases, asthma, and
      other conditions.

PMID- 17234143
TI  - From the smallest virus to the biggest gene: marching towards gene therapy for
      duchenne muscular dystrophy.
AB  - The gene encoding dystrophin, which is altered in Duchenne muscular dystrophy, is
      one of the largest in mammalian species. Adeno-associated virus (AAV) is the
      smallest viral gene delivery vector with a "cargo" capacity of 6 kb and is the
      most effective gene delivery vehicle to muscle cells. Overlapping and trans
      splicing AAV vector approaches are devised to do the "impossible."

PMID- 17234145
TI  - Targeting the messengers of death: the advent of selective activation of
      apoptosis for cancer therapy.
AB  - Apoptosis is a ubiquitous, highly coordinated process of self-destruction.
      Conventional cancer therapeutic agents can cause, to a certain degree, apoptosis
      of cancer cells. However, they do so in an indiscriminate manner leading to
      unacceptable side effects. Strategies of selectively activating apoptosis of
      cancer cells are described.

PMID- 17234146
TI  - Neutrophils as potential therapeutic targets in sepsis.
AB  - Neutrophils are important, expeditious front-line "soldiers" in fighting against
      bacterial infection. In sepsis, the overwhelming immune response to bacterial
      infection precipitates systemic inflammation and organ dysfunction. Neutrophils
      release many lysis-inducing factors and cause local tissue damage, and
      neutrophils themselves became a target in controlling sepsis.

PMID- 17234147
TI  - Targeting E2F1 death signaling: opposing role in cancer control and
      neurodegeneration.
AB  - As with many other molecular agents that are involved in multiple aspects of
      cellular processes, E2F1 plays a dual role of cellular proliferation and
      apoptosis. How to take advantage of the apoptosis induction and sensitization
      properties of E2F1 for therapeutic purposes while minimizing its other properties
      has a significant bearing on how to turn a functionally complex molecule such as
      E2F1 into a drug target.

PMID- 17234148
TI  - Spectrophotometric assay for horseradish peroxidase activity based on
      pyrocatechol-aniline coupling hydrogen donor.
AB  - The hydrogen donor couples pyrocatechol-aniline and phenol-aminoantipyrine in the
      presence of hydrogen peroxide were compared as chromogens for horseradish
      peroxidase (HRP) assay. UV-Visible spectroscopy and high-performance liquid
      chromatography analysis indicated that during the HRP biocatalytic process,
      pyrocatechol-aniline was converted to a pink-colored reagent with a lambda(max)
      of 510 nm, which was used in the assay of HRP activity. Electrochemical studies
      revealed adequate electron transfer ability for this color reagent to serve as a
      proper mediator for HRP also. Using pyrocatechol-aniline a higher sensitivity and
      lower detection limit was obtained relative to those of the phenol
      aminoantipyrine couple, which is commonly used for HRP assay. A relative standard
      deviation of 2.9% was obtained for 20 HRP activity measurements, indicating a
      satisfactory reproducibility for this method. In addition, kinetic parameters of
      K(m) (12.5mM) and V(max) (12.2 mM min(-1)mg(-1)) were calculated for pyrocatechol
      aniline. Regarding the superiority of pyrocatechol-aniline, this couple is
      suggested to be a better hydrogen donor for the HRP spectrophotometric assay.

PMID- 17234149
TI  - Expression of Nox1 in 3T3 cells increases cellular acid production but not proton
      conductance.
AB  - The role of the NADPH oxidase homolog 1 (Nox1) in plasma membrane H(+)
      conductance and cellular H(+) production was investigated in 3T3 cells stably
      expressing Nox1 (Nox1 3T3) compared to vector-expressing control cells (mock
      3T3). In whole cell patch clamp experiments both Nox1 and mock 3T3 expressed a
      similar H(+) conductance (Nox1 3T3, 13.2+/-8.6 pS/pF; mock 3T3, 16.6+/-13.4
      pS/pF) with a number of similar characteristics (e.g., current-voltage relations,
      current activation kinetics, Zn(2+)-sensitivity). When the intracellular pH of
      cells was alkalinized with NH(4)Cl, rates of intracellular acidification were
      significantly higher in Nox1 3T3 compared to mock 3T3. Nox1 3T3 showed a time
      course of acidification that followed a double-exponential function with a fast
      and a slow component of, on average, tau=165 s and 1780 s, whereas mock 3T3
      showed only a single slow tau of 1560 s. Expression of Nox1 also caused cells to
      acidify the extracellular medium at higher rates than control cells; Nox1 3T3
      released 96+/-19 fmol h(-1)cell(-1) of acid equivalents compared to 19+/-12 fmol
      h(-1)cell(-1) in mock 3T3. These data show that expression of Nox1 results in a
      mechanism that has the capacity to rapidly acidify the cytosol and generate
      significant amounts of acid. No significant effect of Nox1 expression on the
      plasma membrane H(+) conductance was found.

PMID- 17234150
TI  - Regulation of mRNA stability through a pentobarbital-responsive element.
AB  - Pentobarbital, a general anesthetic and non-genotoxic carcinogen, can induce gene
      expression by activating transcription. In the Drosophila glutathione S
      transferase D21 (gstD21) gene, pentobarbital's regulatory influence extends to
      the level of mRNA turnover. Transcribed from an intronless gene, gstD21 mRNA is
      intrinsically very labile. But exposure to pentobarbital renders it stabilized
      beyond what can be attributed to transcriptional activation. We aim here to
      identify cis-acting element(s) of gstD21 mRNA as contributors to the molecule's
      pentobarbital-mediated stabilization. In the context of hsp70 5'UTR and the 3'UTR
      of act5C, gstD21 mRNA, minus its native UTRs, is stable. Maintaining the same
      context of heterologous UTRs, we can reconstitute using the full-length gstD21
      sequence the inherent instability of gstD21 mRNA and its stabilization by
      pentobarbital. Transgenic flies that express these chimeric gstD21 mRNA exhibit
      decay intermediates lacking 3'UTR, which are not stabilized by PB treatment. The
      3'UTR sequence, when inserted downstream from a reporter transcript, stabilizes
      it 1.6-fold under PB treatment. The analysis of the decay intermediates suggests
      a polysome-associated decay pattern. We propose a regulatory model that features
      a 59-nucleotide pentobarbital-responsive element (PBRE) in the 3'UTR of gstD21
      mRNA.

PMID- 17234151
TI  - Muscle contraction accelerates IL-6 mRNA expression in the rat masseter muscle.
AB  - OBJECTIVE: This study was conducted to determine if interleukin-6 (IL-6) and
      interleukin-1beta (IL-1beta) mRNA expression increase in response to muscle
      contraction caused by repetitive electrical stimulation of the rat masseter
      muscle. METHODS: Male Wistar rats weighing 140-160 g were divided randomly into
      the following three groups: electrical stimulation (ES) group (n=21), carrageenan
      injection (CI) group (n=24), and ES under dantrolene sodium (muscle relaxant)
      injection (ESDI) group (n=7). ES or CI was done to the left masseter; and mock ES
      or mock CI to the right. Muscle tissues on both sides were sampled for total RNA
      isolation. Real-time RT-PCR was performed, with the cyclophilin A (CypA) mRNA
      level in each sample as an internal control. Mean relative IL-6 (il-6/cypA) and
      IL-1beta (il-1beta/cypA) mRNA levels were compared between the experimental and
      mock-treated sides within each group. RESULTS: Mean IL-6/CypA levels in the ES-
      or CI-treated muscle significantly increased, without any significant incremental
      change observed in either mock-treated muscle. Interestingly, the increase in the
      il-6/cypA level caused by the ES was suppressed by the injection of dantrolene
      sodium in the ESDI group. Furthermore, the mean il-1beta/cypA level in the CI
      treated masseter also significantly increased without any significant incremental
      change observed in the mock-treated muscle. However, there was no significant
      difference in the mean il-1beta/cypA levels in the masseter between the ES- and
      the mock-treated sides. CONCLUSIONS: These results show that IL-6 mRNA expression
      in the rat masseter muscle was accelerated by the CI or by repetitive muscle
      contraction induced by ES. Since the mRNA level of IL-1beta, a well-known
      proinflammatory cytokine, was not altered by the contraction, the accelerated IL
      6 mRNA expression elicited by the muscle contraction does not seem to be related
      to local inflammation.

PMID- 17234152
TI  - Psychrophily is associated with differential energy partitioning, photosystem
      stoichiometry and polypeptide phosphorylation in Chlamydomonas raudensis.
AB  - Chlamydomonas raudensis UWO 241 and SAG 49.72 represent the psychrophilic and
      mesophilic strains of this green algal species. This novel discovery was
      exploited to assess the role of psychrophily in photoacclimation to growth
      temperature and growth irradiance. At their optimal growth temperatures of 8
      degrees C and 28 degrees C respectively, UWO 241 and SAG 49.72 maintained
      comparable photostasis, that is energy balance, as measured by PSII excitation
      pressure. Although UWO 241 exhibited higher excitation pressure, measured as 1
      qL, at all growth light intensities, the relative changes in 1-qL were similar to
      that of SAG 49.72 in response to growth light. In response to suboptimal
      temperatures and increased growth irradiance, SAG 49.72 favoured energy
      partitioning of excess excitation energy through inducible, down regulatory
      processes (Phi(NPQ)) associated with the xanthophyll cycle and antenna quenching,
      while UWO 241 favoured xanthophyll cycle-independent energy partitioning through
      constitutive processes involved in energy dissipation (Phi(NO)). In contrast to
      SAG 49.72, an elevation in growth temperature induced an increase in PSI/PSII
      stoichiometry in UWO 241. Furthermore, SAG 49.72 showed typical threonine
      phosphorylation of LHCII, whereas UWO 241 exhibited phosphorylation of
      polypeptides of comparable molecular mass to PSI reaction centres but the absence
      of LHCII phosphorylation. Thus, although both strains maintain an energy balance
      irrespective of their differences in optimal growth temperatures, the mechanisms
      used to maintain photostasis were distinct. We conclude that psychrophily in C.
      raudensis is complex and appears to involve differential energy partitioning,
      photosystem stoichiometry and polypeptide phosphorylation.

PMID- 17234153
TI  - A role for mrgA, a DPS family protein, in the internal transport of Fe in the
      cyanobacterium Synechocystis sp. PCC6803.
AB  - The mrgA protein of the cyanobacterium Synechocystis sp. PCC6803 is a member of
      the DPS Fe storage protein family. The physiological role of this protein was
      studied using a disruption mutant in the mrgA gene (slr1894) and by measuring
      intracellular Fe quotas, 77K chlorophyll fluorescence and growth rates. It was
      found that the deletion of the mrgA gene did not impair the Fe storage capacity,
      as the intracellular Fe quotas of the DeltamrgA cells were comparable to those of
      the wild type. Furthermore, the cellular response to decreasing external Fe
      concentrations, as detected by the emergence of the CP43' 77K fluorescence band,
      was similar in wild type and mutant cultures. On the other hand, a considerable
      slow down in the growth rate of DeltamrgA cultures was observed upon transfer
      from Fe replete to Fe depleted medium, indicating impeded utilization of the
      plentiful intracellular Fe. Based on these results, we suggest that mrgA plays an
      important role in the transport of intracellular Fe from storage (within
      bacterioferritins) to biosynthesis of metal cofactors throughout the cell's
      growth.

PMID- 17234154
TI  - Heme oxygenase-1 inhibits cytokine production by activated mast cells.
AB  - Heme oxygenase-1 (HO-1) is thought to contribute to host defense reactions
      against various stresses. In addition, recent reports have suggested that HO-1
      modulates immunocyte activation and functions. HO-1 suppresses mast cell
      degranulation, but whether HO-1 suppresses cytokine synthesis as well is not yet
      known. We examined whether rat HO-1 cDNA transfected rat basophilic leukemia
      (RBL)-2H3 cells have altered cytokine production in response to stimulation with
      anti-ovalbumin (OA) serum/OA compared to Mock transfected RBL-2H3 cells. HO-1
      inhibited anti-OA serum/OA-induced IL-3 and TNF-alpha production. Inhibition of
      HO-1 activity by Zn (II) protoporphyrin IX, a specific HO-1 inhibitor, prevented
      the suppression of TNF-alpha production. The cytokine inhibition by HO-1 was
      associated with selective suppression of the DNA-binding activity of AP-1
      transcription factors. The suppression of mast cell cytokine production by HO-1
      may be an important aspect of the processes that lead to resolution of allergic
      inflammation.

PMID- 17234155
TI  - Bone marrow stromal cells stimulate neurite outgrowth over neural proteoglycans
      (CSPG), myelin associated glycoprotein and Nogo-A.
AB  - In animal models, transplantation of bone marrow stromal cells (MSC) into the
      spinal cord following injury enhances axonal regeneration and promotes functional
      recovery. How these improvements come about is currently unclear. We have
      examined the interaction of MSC with neurons, using an established in vitro model
      of nerve growth, in the presence of substrate-bound extracellular molecules that
      are thought to inhibit axonal regeneration, i.e., neural proteoglycans (CSPG),
      myelin associated glycoprotein (MAG) and Nogo-A. Each of these molecules repelled
      neurite outgrowth from dorsal root ganglia (DRG) in a concentration-dependent
      manner. However, these nerve-inhibitory effects were much reduced in MSC/DRG co
      cultures. Video microscopy demonstrated that MSC acted as "cellular bridges" and
      also "towed" neurites over the nerve-inhibitory substrates. Whereas conditioned
      medium from MSC cultures stimulated DRG neurite outgrowth over type I collagen,
      it did not promote outgrowth over CSPG, MAG or Nogo-A. These findings suggest
      that MSC transplantation may promote axonal regeneration both by stimulating
      nerve growth via secreted factors and also by reducing the nerve-inhibitory
      effects of the extracellular molecules present.

PMID- 17234156
TI  - Trichostatin A blocks TGF-beta-induced collagen gene expression in skin
      fibroblasts: involvement of Sp1.
AB  - Transforming growth factor- beta (TGF-beta) stimulates Type I collagen synthesis
      by fibroblasts and is implicated in tissue fibrosis. Here, we demonstrate that
      histone deacetylase inhibitor Trichostatin A (TSA) suppresses the TGF-beta
      induced Type I collagen synthesis but not induced PAI-1 synthesis suggesting the
      influence of TSA is gene specific. Results further reveal that there is no
      significant alteration in Smad activation and function in presence of TSA
      suggesting suppression of TGF-beta-induced collagen synthesis is not due to
      impaired Smad signaling. TGF-beta induces the levels of Sp1, an essential
      transcription factor of Smad-dependent stimulation of collagen synthesis.
      However, in presence of TSA, TGF-beta fails to induce Sp1 levels, its interaction
      with Smad complex and Sp1 binding site in COL1A2 promoter. Furthermore,
      overexpressed Sp1 reverses the TSA-mediated inhibition of TGF-beta-induced
      collagen gene expression. Collectively, these results suggest that TSA-mediated
      suppression of Smad-dependent TGF-beta-induced collagen synthesis is due to
      suppression of Sp1 activity in skin fibroblasts.

PMID- 17234157
TI  - Abiotic and biotic stress tolerance in Arabidopsis overexpressing the
      multiprotein bridging factor 1a (MBF1a) transcriptional coactivator gene.
AB  - We conducted a genetic yeast screen to identify salt tolerance (SAT) genes in a
      maize kernel cDNA library. During the screening, we identified a maize clone
      (SAT41) that seemed to confer elevated salt tolerance in comparison to control
      cells. SAT41 cDNA encodes a 16-kDa protein which is 82.4% identical to the
      Arabidopsis Multiprotein bridging factor 1a (MBF1a) transcriptional coactivator
      gene. To further examine salinity tolerance in Arabidopsis, we functionally
      characterized the MBF1a gene and found that dehydration as well as heightened
      glucose (Glc) induced MBF1a expression. Constitutive expression of MBF1a in
      Arabidopsis led to elevated salt tolerance in transgenic lines. Interestingly,
      plants overexpressing MBF1a exhibited insensitivity to Glc and resistance to
      fungal disease. Our results suggest that MBF1a is involved in stress tolerance as
      well as in ethylene and Glc signaling in Arabidopsis.

PMID- 17234158
TI  - Pirfenidone inhibits TGF-beta expression in malignant glioma cells.
AB  - Due to its immunosuppressive properties, the cytokine transforming growth factor
      (TGF)-beta has become a promising target in the experimental treatment of human
      malignant gliomas. Here, we report that the antifibrotic drug 5-methyl-1-phenyl-2
      (1H)-pyridone (pirfenidone, PFD) elicits growth-inhibitory effects and reduces
      TGF-beta2 protein levels in human glioma cell lines. This reduction in TGF-beta2
      is biologically relevant since PFD treatment reduces the growth inhibition of TGF
      beta-sensitive CCL-64 cells mediated by conditioned media of glioma cells. The
      downregulation of TGF-beta is mediated at multiple levels. PFD leads to a
      reduction of TGF-beta2 mRNA levels and of the mature TGF-beta2 protein due to
      decreased expression and direct inhibition of the TGF-beta pro-protein convertase
      furin. In addition, PFD reduces the protein levels of the matrix
      metalloproteinase (MMP)-11, a TGF-beta target gene and furin substrate involved
      in carcinogenesis. These data define PFD or PFD-related agents as promising
      agents for human cancers associated with enhanced TGF-beta activity.

PMID- 17234159
TI  - The activation by estrogen receptor agonists of the BK(Ca)-channel in human
      cardiac fibroblasts.
AB  - The agonists selective for estrogen receptor (ER)-alpha (4,4',4''-(4-propyl
      [(1)H]-pyrazole-1,3,5-triyl) tris-phenol, PPT) and ER-beta (2,3-bis(4
      hydroxyphenyl)-propionitrile, DPN) are known to stimulate ER-alpha and ER-beta
      receptors, respectively. It remains unknown whether these two agents regulate the
      activity of ion channels via a direct stimulation. In this study, we tested the
      hypothesis that DPN or PPT stimulates the large-conductance Ca(2+)-activated K(+)
      (BK(Ca)) channels in cultured human cardiac fibroblasts (HCFs). In whole-cell
      configuration, depolarizing pulses evoked K(+) outward currents in an outward
      rectification in HCFs, the amplitude of which was increased in the presence of
      DPN or PPT. In inside-out patches, the activity of BK(Ca)-channel with a
      conductance of 167+/-8 pS was observed in these cells. PPT or DPN applied to the
      intracellular face of the membrane enhanced the activity of BK(Ca) channels with
      no change in single-channel conductance. DPN and PPT increased BK(Ca)-channel
      activity with an EC(50) value of 2.3 and 2.6 microM, respectively. The mean
      closed time of these channels during the exposure to these compounds was reduced
      with no change in the gating charge of the channels. Intracellular Ca(2+) was not
      altered by these two compounds. RT-PCR analysis revealed that no change in the
      transcriptional level of the BK(Ca)-channel alpha-subunit was observed in chronic
      treatment with these two compounds. PPT- and DPN-stimulated increase in BK(Ca)
      channels reveal novel pharmacological properties attributable to the activity of
      these channels, and their increase in BK(Ca) channels activity in HCFs may
      contribute to cell function.

PMID- 17234160
TI  - Differences in the cellular response and signaling pathways of cisplatin and
      BBR3464 ([[trans-PtCl(NH3)(2)]2mu-(trans-Pt(NH3)(2)(H2N(CH2)(6)-NH2)2)]4+)
      influenced by copper homeostasis.
AB  - [[trans-PtCl(NH(3))(2)](2)mu-(trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)-NH(2))(2))](4+)
      (BBR3464) is a cationic trinuclear platinum drug that is being evaluated in phase
      II clinical trials for treatment of lung and ovarian cancers. The structure and
      DNA binding profile of BBR3464 is different from drugs commonly used clinically.
      It is of great interest to evaluate the difference between the mechanisms of
      uptake employed by BBR3464 and cisplatin (c-DDP), as altered uptake may explain
      chemoresistance. Using transfected cell lines, we show that both c-DDP and
      BBR3464 use the copper transporter hCTR1 to enter cells and to a lesser extent,
      the ATP7B transporter to exit cells. Copper influenced c-DDP and BBR3464 uptake
      similarly; it increased the c-DDP and BBR3464 uptake in ovarian (A2780) and
      colorectal (HCT116) carcinoma cell lines as detected by ICP-OES. However, the
      effects of copper on c-DDP- and BBR3464-mediated cytotoxicity differed. Copper
      decreased c-DDP-induced apoptosis, caspase-3/7 activation, p53 induction and PARP
      cleavage in cancer cell lines. In contrast, copper increased BBR3464-induced
      apoptosis, and had little effect on caspase activation, PARP cleavage, and p53
      induction. It was concluded that BBR3464 employs mechanisms of intracellular
      action distinct from c-DDP. Although these drugs use the same cellular
      transporters (hCTR1 and ATP7B) for influx and efflux, downstream effects are
      different for the two drugs. These experiments illustrate fundamental differences
      in the mechanisms of action between cisplatin and the novel Pt-based drug
      BBR3464.

PMID- 17234161
TI  - A comparison between spontaneous electroencephalographic activities induced by
      morphine and morphine-related environment in rats.
AB  - Previous studies demonstrated that drug cues could elicit drug-like or withdrawal
      like effect, both subjectively and physiologically. However, few studies have
      compared the central activities induced by a drug-related environment and the
      drug itself. The aim of this study was to observe and compare
      electroencephalographic (EEG) changes induced by acute morphine administration
      and by the morphine-related environment. EEG activities were recorded via twelve
      skull electrodes scattered on the left and right cortex in conscious, freely
      moving rats, either after acute morphine administration or after successful
      training of conditioned place preference. Acute administration of morphine (0.1,
      0.5, 1, 5, 10, 20 mg/kg, i.p.) produced an increase in absolute EEG power in the
      delta, theta, alpha1, alpha2, beta1, and beta2 bands, as well as a decrease in
      the gamma band. Topographic mapping revealed a maximal increase in the lateral
      leads in the theta band and a maximal change in the centro-frontal region in the
      remaining bands. After place conditioning training, the morphine-related
      environment induced a diffuse decrease in absolute power in the delta, theta,
      alpha1, alpha2, beta1, and beta2 bands, which was opposite to the changes induced
      by acute morphine administration. In addition, the changes in relative power
      induced by the two situations also diverged. These results indicate that the
      central mechanisms underlying the motivation of morphine-induced place preference
      may be somehow different from those underlying the reward effects produced by
      acute morphine administration.

PMID- 17234162
TI  - Increased phosphorylation of caveolin-1 in the sciatic nerves of Lewis rats with
      experimental autoimmune neuritis.
AB  - The levels of phosphorylated caveolin-1 (p-caveolin-1) were analyzed in the
      sciatic nerves of Lewis rats with experimental autoimmune neuritis (EAN). Western
      blot analysis showed that the phosphorylation of caveolin-1 increased
      significantly in the sciatic nerves of EAN-affected rats at the paralytic stage
      of EAN on day 14 post-immunization (PI) (P<0.05) and declined slightly thereafter
      during the recovery stage. Immunohistochemistry showed intense p-caveolin-1
      immunostaining in some inflammatory macrophages, as well as in T-cells in
      individual nerve fascicles at the peak stage of EAN, while p-caveolin-1 was
      weakly expressed in some of the vascular endothelial cells and Schwann cells of
      normal sciatic nerves. The inflammatory cells with intense p-caveolin-1
      expression in the EAN-affected individual nerve fascicles were not positive for
      terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL),
      while the TUNEL-positive apoptotic cells in the perineurium, where infiltration
      initially occurred, were weakly positive for p-caveolin-1. Based on these
      findings, we postulate that caveolin-1 is phosphorylated in inflammatory cells
      soon after they infiltrate the sciatic nerve, as well as in the perineurium, and
      that p-caveolin-1 activates intracellular signaling in inflammatory cells,
      leading to cell death, which ultimately eliminates the infiltrating inflammatory
      cells from the sciatic nerves of animals with EAN.

PMID- 17234163
TI  - Release of GABA and activation of GABA(A) in the spinal cord mediates the effects
      of TENS in rats.
AB  - Transcutaneous electrical nerve stimulation (TENS) is a commonly utilized non
      pharmacological, non-invasive treatment for pain. GABA is a neurotransmitter in
      the dorsal horn of the spinal cord that mediates analgesia locally, and also
      through activation of supraspinal sites. TENS reduces hyperalgesia through
      activation of receptor-mediated pathways at the level of the spinal cord, and
      supraspinally. The current study tested the hypothesis that either high or low
      frequency TENS applied to the inflamed knee joint increases GABA in the spinal
      cord dorsal horn and activates GABA receptors spinally. We utilized microdialysis
      to sample the extracellular fluid before, during and after TENS and analyzed GABA
      in dialysates with high performance liquid chromatography. We analyzed the
      extracellular GABA concentrations in animals with and without knee joint
      inflammation induced by intra-articular injection of kaolin and carrageenan. We
      further tested if spinal blockade of GABA receptors prevents the antihyperalgesia
      produced by TENS in rats with joint inflammation. We show that high frequency
      TENS increases extracellular GABA concentrations in the spinal cord in animals
      with and without joint inflammation. The increases in GABA do not occur in
      response to low frequency TENS, and there are no increases in glycine in response
      to low or high frequency TENS. However, the reduction in primary hyperalgesia by
      both high and low frequency TENS is prevented by spinal blockade of GABA(A)
      receptors with bicuculline. Thus, high frequency TENS increases release of GABA
      in the deep dorsal horn of the spinal cord, and both high and low frequency TENS
      reduce primary hyperalgesia by activation of GABA(A) receptors spinally.

PMID- 17234164
TI  - Functionalization of oligosaccharide mimetics and multimerization using squaric
      diester-mediated coupling.
AB  - Functionalized carbohydrate-centered glycoclusters formed the starting material
      for the synthesis of tagged oligosaccharide and glycoconjugate mimetics, which
      were obtained by thiourea-bridging, peptide coupling and in particular squaric
      diester-mediated coupling. The latter method could also be utilized to provide
      new multivalent glycoconjugates, which were tested for their anti-adhesive
      properties in an ELISA with Escherichia coli bacteria.

PMID- 17234165
TI  - Enantioseparation of some chiral flavanones using microbial cyclic beta-(1-
      >3),(1-->6)-glucans as novel chiral additives in capillary electrophoresis.
AB  - Cyclic beta-(1-->3),(1-->6)-glucans, microbial cyclooligosaccharides produced by
      Bradyrhizobium japonicum USDA 110, were used as novel chiral additives for the
      enantiomeric separation of some flavanones such as eriodictyol, homoeriodictyol,
      hesperetin, naringenin, and isosakuranetin in capillary electrophoresis (CE).
      Among the flavanones, eriodictyol was separated with the highest resolution (R(s)
      5.66) and selectivity factor (alpha 1.18) when 20mM cyclic beta-(1-->3),(1-->6)
      glucans were added to the background electrolyte (BGE) at pH 8.3.

PMID- 17234166
TI  - Synthesis and structure of glycans. Special thematic issue to commemorate Nikolay
      Konstantinovich Kochetkov on the first anniversary of his death.

PMID- 17234167
TI  - Impaired perfusion after myocardial infarction is due to reperfusion-induced
      deltaPKC-mediated myocardial damage.
AB  - OBJECTIVE: To improve myocardial flow during reperfusion after acute myocardial
      infarction and to elucidate the molecular and cellular basis that impedes it.
      According to the AHA/ACC recommendation, an ideal reperfusion treatment in
      patients with acute myocardial infarction (AMI) should not only focus on
      restoring flow in the occluded artery, but should aim to reduce microvascular
      damage to improve blood flow in the infarcted myocardium. METHODS: Transgenic
      mouse hearts expressing the deltaPKC (protein kinase C) inhibitor, deltaV1-1, in
      their myocytes only were treated with or without the deltaPKC inhibitor after
      ischemia in an ex vivo AMI model. deltaV1-1 or vehicle was also delivered at
      reperfusion in an in vivo porcine model of AMI. Microvascular dysfunction was
      assessed by physiological and histological measurements. RESULTS: deltaPKC
      inhibition in the endothelial cells improved myocardial perfusion in the
      transgenic mice. In the porcine in vivo AMI model, coronary flow reserve (CFR),
      which is impaired for 6 days following infarction, was improved immediately
      following a one-minute treatment at the end of the ischemic period with the
      deltaPKC-selective inhibitor, deltaV1-1 ( approximately 250 ng/kg), and was
      completely corrected by 24 h. Myocardial contrast echocardiography, electron
      microscopy studies, and TUNEL staining demonstrated deltaPKC-mediated
      microvascular damage. epsilonPKC-induced preconditioning, which also reduces
      infarct size by >60%, did not improve microvascular function. CONCLUSIONS: These
      data suggest that deltaPKC activation in the microvasculature impairs blood flow
      in the infarcted tissue after restoring flow in the occluded artery and that AMI
      patients with no-reflow may therefore benefit from treatment with a deltaPKC
      inhibitor given in conjunction with removal of the coronary occlusion.

PMID- 17234168
TI  - Insulin augments matrix metalloproteinase-9 expression in monocytes.
AB  - OBJECTIVE: Insulin resistance and hyperinsulinemia are major causes of
      cardiovascular morbidity and mortality. Matrix metalloproteinases (MMPs), highly
      expressed in activated mononuclear cells in vulnerable atherosclerotic lesions,
      are the main proteolytic enzymes controlling plaque stability. The aim of this
      study was to investigate the regulation of monocyte MMP-9 by insulin. METHODS AND
      RESULTS: Stimulation of MMP-9 expression by insulin was time- and concentration
      dependent in human monocytic THP-1 cells. Inhibition of insulin receptor (IR)
      maturation via inhibition of its activating convertase furin with the
      pharmacological furin-inhibitor decanoyl-RVKR-chloromethylketone, as well as
      blocking of IGF-1R function with a IGF-1R blocking antibody, demonstrated that
      insulin mediates increases in MMP-9 via IR activation. Inhibition of insulin's
      "metabolic" phosphatidylinositol 3-kinase signaling with wortmannin (50 nmol/L)
      or LY294002 (2.5 micromol/L) did not prevent insulin-dependent MMP-9 induction.
      In contrast inhibition of insulin's "mitogenic" Ras-Raf-mitogen-activated protein
      kinase-kinase pathways with PD98059 (15 micromol/L) or U0126 (2 micromol/L)
      inhibited insulin-induced MMP-9 gelatinolytic activity in THP-1 cells. Likewise,
      PD98059 inhibited insulin augmented MMP-9 levels in primary human monocytes,
      whereas wortmannin had no effect. CONCLUSION: This study demonstrates that
      insulin can induce MMP-9 via mitogenic signaling pathways in monocytes, whereas
      phosphatidylinositol 3-kinase-dependent signaling, typically altered in insulin
      resistance, is not required. Induction of MMP-9 by insulin may potentially
      contribute to a pro-inflammatory state and the increased cardiovascular morbidity
      and mortality in type 2 diabetics.

PMID- 17234169
TI  - Chloroprene: overview of studies under consideration for the development of an
      IRIS assessment.
AB  - Beta-chloroprene (C(4)H(5)Cl, chloroprene, 2-chloro-1,3-butadiene, CASRN 126-99
      8) is a volatile, flammable liquid monomer utilized primarily in the manufacture
      of neoprene (polychloroprene) elastomer used in belts, hoses, gloves, wire
      coatings, and tubing. Absorption into the body occurs primarily via the
      respiratory system and may occur via the gastrointestinal tract or the skin. Once
      absorbed, chloroprene is widely distributed as evidenced by effects in several
      target organs including nose and lung, liver, and skin. Chloroprene metabolism is
      believed to include cytochrome P450 oxidation to a monoepoxide, hydrolysis by
      epoxide hydrolases, and glutathione conjugation. Similar to 1,3-butadiene, the
      epoxide is considered to be the toxic moiety, and species differences in
      metabolic capacity may influence the severity of effects as well as what tissues
      are affected. EPA has not previously developed an assessment of chloroprene's
      potential for human health effects. Existing human epidemiological studies offer
      little data on noncancer effects, and the associations of exposure with increased
      cancer (liver and lung) mortality reported are inconclusive. Recent
      epidemiological studies (submitted for publication) could offer information that
      may impact chloroprene's health assessment. Multiple-site tumors have been
      reported in rats and mice exposed to chloroprene by inhalation; nevertheless,
      there are marked differences in strain sensitivities (i.e., tumors in F344 rats
      versus no tumors in Wistar rats). Recently developed physiologically based
      toxicokinetic models may allow for the resolution of species and tissue
      differences and sensitivities as well as exposure-dose-response relationships
      relevant to humans. (This presentation does not necessarily reflect EPA policy.).

PMID- 17234170
TI  - Relationship between serum levels of vascular endothelial growth factor,
      hepatocyte growth factor and matrix metalloproteinase-9 with biochemical markers
      of bone disease in multiple myeloma.
AB  - BACKGROUND: Multiple myeloma is characterized by accumulation of plasma cells in
      the bone marrow, with osteolysis and increased marrow angiogenesis. We studied
      molecules involved in angiogenesis (MMP-9, HGF, VEGF) in relation to disease
      stage, extent of bone destruction, and markers of bone turnover (Ntx and PICP).
      METHODS: MMP-9, HGF, VEGF were measured in the serum of 42 newly diagnosed
      myeloma patients and 24 controls with commercial ELISA kits. Urinary levels of
      Ntx were measured by ELISA, and serum PICP with RIA. Extent of radiological bone
      disease was graded into low and high score. Stage was estimated according to the
      Durie-Salmon criteria. RESULTS: HGF, VEGF and Ntx were higher in patients than
      controls (p<0.001). MMP-9 and PICP did not differ between patients and controls.
      HGF, VEGF, MMP-9 and Ntx increased significantly with disease stage (I to III,
      p<0.001) and PICP decreased significantly with advancing stage (p<0.05). There
      was a positive correlation between HGF and MMP-9 (r: 0.36, p<0.01), VEGF and MMP
      9 (r: 0.38, p<0.01), Ntx and MMP-9 (r: 0.39, p<0.01) and an inverse correlation
      between PICP and MMP-9 (r: -0.66, p<0.0001). CONCLUSIONS: Angiogenesis and bone
      destruction are closely interrelated in myeloma, and cytokine levels (MMP-9, VEGF
      and HGF) may be useful in monitoring progression.

PMID- 17234171
TI  - Differential effect of blood collection tubes on total free fatty acids (FFA) and
      total triiodothyronine (TT3) concentration: a model for studying interference
      from tube constituents.
AB  - BACKGROUND: Besides total triiodothyronine (TT3), total free fatty acids (FFA)
      concentrations were higher with serum separator tube (SST) than Vacuette tubes.
      METHODS: The effects of surfactant, rubber stopper, and separator gel from
      various tubes were investigated on FFA, beta-hydroxybutyrate (beta-HB), and TT3
      with 8 different tube types in blood specimens of apparently healthy volunteers.
      RESULTS: Compared to Vacuette tubes, serum FFA and TT3 concentrations were
      significantly higher in SST than glass tubes. Reformulated SST eliminated the
      increase in TT3 but not FFA. No significant difference was observed for beta-HB
      concentration among tube types. Surfactant and rubber stoppers from the different
      tube types significantly increased TT3 but not FFA and beta-HB concentrations.
      Agitation of whole blood but not serum or plasma specimens with separator gel
      from SST, reformulated SST and plasma preparation tube (PPT) tubes compared to
      Vacuette tubes gave higher FFA but not beta-HB levels. CONCLUSIONS: Unidentified
      component(s) from the separator gel in SST, reformulated SST and PPT tubes cause
      falsely high FFA concentration. In contrast to TT3, falsely high FFA results
      require exposure of whole blood and not serum to tube constituent(s). The
      approach employed here may serve as a model for assessing interference(s) from
      tube constituent(s).

PMID- 17234172
TI  - How to estimate GFR-serum creatinine, serum cystatin C or equations?
AB  - Plasma or serum creatinine is the most commonly used diagnostic marker for the
      estimation of glomerular filtration rate (GFR) in clinical routine. Due to
      substantial pre-analytical and analytical interferences and limitations,
      creatinine cannot be considered accurate. Besides, the diagnostic sensitivity to
      detect moderate GFR reduction is insufficient. Equations to estimate GFR based on
      serum creatinine have been introduced, which included anthropometric data to
      compensate for the limitations of creatinine. Most validated and applied are the
      MDRD and the Cockcroft-Gault equation for adults, and the Schwartz equation for
      children. These equations can be calculated at the bedside or issued by the
      laboratory and provide accurate GFR estimates from 20 to 60 mL/min/1.73 m(2) with
      good accuracy but moderate to poor bias and precision. Further limiting is the
      lack of creatinine reference methods and of calibration material. Lately, the low
      molecular weight protein cystatin C was introduced as a GFR estimate superior to
      creatinine. In particular, serum cystatin C is sensitive to detect mild GFR
      reduction between 60 and 90 mL/min/1.73 m(2). However, no reference method and no
      uniform calibration material exist for cystatin C either. Further limitations are
      the effect of thyroid dysfunction, of high glucocorticoid doses and potentially
      the presence of cardiovascular diseases on cystatin C levels. To evade these
      obstacles and to further improve GFR estimation, cystatin C-based equations have
      been proposed, which seem to be superior to creatinine-based ones. However, this
      issue requires further evaluation. We propose a panel of GFR markers to
      facilitate the detection of reduced GFR at various stages and in different
      populations; this however needs to be extended and refined in the near future. In
      principle, clinicians should be aware of the limitations of and cautioned not to
      overrate estimated GFR by single markers or calculated by equations and should
      not entirely rely on GFR estimates to make precise clinical decisions.

PMID- 17234173
TI  - Changing a limb muscle growth program into a resorption program.
AB  - Transgenic Xenopus laevis tadpoles that express a dominant negative form of the
      thyroid hormone receptor (TRDN) controlled by the cardiac actin muscle promoter
      (pCar) develop with very little limb muscle. Under the control of the
      tetracycline system the transgene can be induced at will by adding doxycycline to
      the rearing water. Pre-existing limb muscle fibers begins to disintegrate within
      2 days after up-regulation of the TRDN transgene. The muscle cells do not die
      even after weeks of transgene exposure when the myofibrils have degenerated
      completely and the tadpole is nearing death. A microarray analysis after 2 weeks
      of exposure to the transgene identified 24 muscle genes whose expression was
      altered in such a way that they might cause the muscle phenotype. These candidate
      genes are normally activated in growing limb muscle but they are repressed by the
      TRDN transgene. Several of these genes have been implicated in mammalian
      myopathies. However, the expression of only one of these genes, calsequestrin, is
      down-regulated in 1 day and therefore might initiate the degeneration.
      Calsequestrin is one of several affected genes that encode proteins involved in
      calcium sequestration, transport and utilization in muscle suggesting that
      uncontrolled calcium influx into the growing limb muscle fibers causes
      rhabdomyolysis. Many of the same genes that are down-regulated in the tail at the
      peak of metamorphic climax just before it is resorbed are suppressed in the
      transgenic limb muscle in effect turning the limb growth program into a tail
      resorption program.

PMID- 17234175
TI  - The RNA-binding proteins PUF-5, PUF-6, and PUF-7 reveal multiple systems for
      maternal mRNA regulation during C. elegans oogenesis.
AB  - In metazoans, many mRNAs needed for embryogenesis are produced during oogenesis
      and must be tightly regulated during the complex events of oocyte development. In
      C. elegans, translation of the Notch receptor GLP-1 is repressed during oogenesis
      and is then activated specifically in anterior cells of the early embryo. The KH
      domain protein GLD-1 represses glp-1 translation during early stages of meiosis,
      but the factors that repress glp-1 during late oogenesis are not known. Here, we
      provide evidence that the PUF domain protein PUF-5 and two nearly identical PUF
      proteins PUF-6 and PUF-7 function during a specific period of oocyte
      differentiation to repress glp-1 and other maternal mRNAs. Depletion of PUF-5 and
      PUF-6/7 together caused defects in oocyte formation and early embryonic cell
      divisions. Loss of PUF-5 and PUF-6/7 also caused inappropriate expression of GLP
      1 protein in oocytes, but GLP-1 remained repressed in meiotic germ cells. PUF-5
      and PUF-6/7 function was required directly or indirectly for translational
      repression through elements of the glp-1 3' untranslated region. Oogenesis and
      embryonic defects could not be rescued by loss of GLP-1 activity, suggesting that
      PUF-5 and PUF-6/7 regulate other mRNAs in addition to glp-1. PUF-5 and PUF-6/7
      depletion, however, did not perturb repression of the maternal factors GLD-1 and
      POS-1, suggesting that subsets of maternal gene products may be regulated by
      distinct pathways. Interestingly, PUF-5 protein was detected exclusively during
      mid to late oogenesis but became undetectable prior to completion of oocyte
      differentiation. These results reveal a previously unknown maternal mRNA control
      system that is specific to late stages of oogenesis and suggest new functions for
      PUF family proteins in post-mitotic differentiation. Multiple sets of RNA-binding
      complexes function in different domains of the C. elegans germ line to maintain
      silencing of Notch/glp-1 and other mRNAs.

PMID- 17234174
TI  - A molecular analysis of neurogenic placode and cranial sensory ganglion
      development in the shark, Scyliorhinus canicula.
AB  - In order to gain insight into the evolution of the genetic control of the
      development of cranial neurogenic placodes and cranial sensory ganglia in
      vertebrates, we cloned and analysed the spatiotemporal expression pattern of six
      transcription factor genes in a chondrichthyan, the shark Scyliorhinus canicula
      (lesser-spotted dogfish/catshark). As in other vertebrates, NeuroD is expressed
      in all cranial sensory ganglia. We show that Pax3 is expressed in the profundal
      placode and ganglion, strongly supporting homology between the separate profundal
      ganglion of elasmobranchs and basal actinopterygians and the ophthalmic
      trigeminal placode-derived neurons of the fused amniote trigeminal ganglion. We
      show that Pax2 is a conserved pan-gnathostome marker for epibranchial and otic
      placodes, and confirm that Phox2b is a conserved pan-gnathostome marker for
      epibranchial placode-derived neurons. We identify Eya4 as a novel marker for the
      lateral line system throughout its development, expressed in lateral line
      placodes, sensory ridges and migrating primordia, neuromasts and
      electroreceptors. We also identify Tbx3 as a specific marker for lateral line
      ganglia in shark embryos. We use the spatiotemporal expression pattern of these
      genes to characterise the development of neurogenic placodes and cranial sensory
      ganglia in the dogfish, with a focus on the epibranchial and lateral line
      placodes. Our findings demonstrate the evolutionary conservation across all
      gnathostomes of at least some of the transcription factor networks underlying
      neurogenic placode development.

PMID- 17234176
TI  - Why polyps regenerate and we don't: towards a cellular and molecular framework
      for Hydra regeneration.
AB  - The basis for Hydra's enormous regeneration capacity is the "stem cellness" of
      its epithelium which continuously undergoes self-renewing mitotic divisions and
      also has the option to follow differentiation pathways. Now, emerging molecular
      tools have shed light on the molecular processes controlling these pathways. In
      this review I discuss how the modular tissue architecture may allow continuous
      replacement of cells in Hydra. I also describe the discovery and regulation of
      factors controlling the transition from self-renewing epithelial stem cells to
      differentiated cells.

PMID- 17234178
TI  - Diurnal temperature range and daily mortality in Shanghai, China.
AB  - Although the relationship between temperature level and mortality outcomes has
      been well established, it is still unknown whether within-day variation in
      temperature, e.g. diurnal temperature range (DTR), is a risk factor for death
      independent of the corresponding temperature. Moreover, DTR is a meteorological
      indicator associated with global climate change which may be related to a variety
      of health outcomes. We hypothesized that large diurnal temperature change might
      be a source of additional environmental stress and therefore a risk factor for
      death. We used daily weather and mortality data from Shanghai, China to test this
      hypothesis. We conducted a time-series study to examine the association between
      DTR and mortality outcomes from 2001 to 2004. A semi-parametric generalized
      additive model (GAM) was used to assess the acute effect of DTR on mortality
      after controlling for covariates including time trend, day of the week (DOW),
      temperature, humidity, and outdoor air pollution. We found a strong association
      between DTR and daily mortality after adjustment for those potential confounders.
      A 1 degrees C increment of the 3-day moving average of DTR corresponded to a
      1.37% (95% CI 1.08-1.65%) increase in total non-accidental mortality, a 1.86%
      (95% CI 1.40-2.32%) increase in cardiovascular mortality, and a 1.29% (95% CI
      0.49-2.09%) increase in respiratory mortality. The effects of DTR on total non
      accidental and cardiovascular mortality were significant on both "cold" (below 23
      degrees C) and "warm" (at least 23 degrees C) days, although respiratory
      mortality was only significantly associated with DTR on "cold" days. This study
      suggests within-day variation in temperature may be a novel risk factor for
      death.

PMID- 17234177
TI  - Tough beginnings: alterations in the transcriptome of cloned embryos during the
      first two cell cycles.
AB  - Cloned embryos produced by somatic cell nuclear transfer (SCNT) display a
      plethora of phenotypic characteristics that make them different from fertilized
      embryos, indicating defects in the process of nuclear reprogramming by the
      recipient ooplasm. To elucidate the extent and timing of nuclear reprogramming,
      we used microarrays to analyze the transcriptome of mouse SCNT embryos during the
      first two cell cycles. We identified a large number of genes mis-expressed in
      SCNT embryos. We found that genes involved in transcription and regulation of
      transcription are prominent among affected genes, and thus may be particularly
      difficult to reprogram, and these likely cause a ripple effect that alters the
      transcriptome of many other functions, including oxidative phosphorylation,
      transport across membrane, and mRNA transport and processing. Interestingly, we
      also uncovered widespread alterations in the maternal (i.e., non-transcribed)
      mRNA population of SCNT embryos. We conclude that gene expression in early SCNT
      embryos is grossly abnormal, and that this is at least in part the result of
      incomplete reprogramming of transcription factor genes.

PMID- 17234179
TI  - Inhibition of eosinophilia in vivo by a small molecule inhibitor of very late
      antigen (VLA)-4.
AB  - The alpha4beta1 integrin (very late antigen-4, VLA-4) plays an important role in
      the migration of lymphocytes, monocytes, and eosinophils, but not neutrophils, to
      sites of inflammation. Pharmacological antagonism of VLA-4 is an attractive
      prospect for the treatment of predominantly eosinophil mediated diseases such as
      asthma and allergic rhinitis. We report here on a potent and selective, small
      molecule VLA-4 inhibitor, (2S)-3-(2', 5'-dichlorobiphenyl-4-yl)-2-({[1-(2
      methoxybenzoyl)piperidin-3-yl]carbonyl}amino) propanoic acid, compound 1, and
      characterize the antagonist activities of this molecule in various cell-based
      assays and in an animal model of eosinophil migration. Compound 1 inhibited VLA
      4/ vascular cell adhesion molecule-1(VCAM-1) interactions with in vitro potencies
      (IC50 value of 210 nM) in VLA-4-expressing Ramos cells, although the compound did
      not inhibit cell adhesion to fibronectin via alpha5beta1 integrin (very late
      antigen-5, VLA-5). Blockade of phorbol-12-myristate-13-acetate (PMA)- or Mn2+
      stimulated VLA-4 interactions with compound 1 was observed in human T lymphocytes
      (IC50 value of 230 nM), human eosinophils (IC50 value of 4.0 microM) and mouse
      eosinophils (IC50 value of 1.6 microM). Furthermore, compound 1 administered by
      intraperitoneal injection inhibited eosinophil infiltration in a dose-dependent
      manner by up to 80% in an air pouch model. These data support the use of small
      molecule VLA-4 antagonists in the treatment of relevant diseases, such as asthma,
      atopic dermatitis, or allergic rhinitis.

PMID- 17234180
TI  - Metalloelastase (MMP-12) induced inflammatory response in mice airways: effects
      of dexamethasone, rolipram and marimastat.
AB  - Direct instillation of a recombinant human form of MMP-12 (rhMMP-12) in mice
      airways elicited an early inflammatory response characterized by neutrophil
      influx, cytokine release and gelatinase activation followed by a delayed
      response, mainly characterized by macrophage recruitment. As this experimental
      model of lung inflammation partially mimics some features of chronic obstructive
      pulmonary disease (COPD), we have investigated the effects of treatment by anti
      inflammatory compounds, dexamethasone and rolipram and a non-specific matrix
      metalloproteinase (MMP) inhibitor, marimastat. The compounds were administrated
      orally, 1 h before rhMMP-12 instillation (8 x 10(-3) U/mouse). Total and
      differential cell counts were evaluated in the bronchoalveolar lavage fluids.
      Cytokines and MMP-9 were quantified in bronchoalveolar lavage fluids and in lung
      homogenate supernatants. Marimastat (100 mg/kg), dexamethasone (10 mg/kg) and
      rolipram (0.1 and 0.3 mg/kg) were able to decrease significantly neutrophil
      recruitment at 4 and 24 h after rhMMP-12 instillation, but only marimastat (30
      and 100 mg/kg) was effective at decreasing the macrophage recruitment occurring
      at day 7. Marimastat (100 mg/kg), dexamethasone (10 mg/kg) and rolipram (0.3
      mg/kg) reduced significantly IL-6, KC/CXCL1, MIP-1alpha/CCL3 and MMP-9 levels in
      bronchoalveolar lavage fluid. Similar results were obtained in lung homogenates
      except with rolipram. Dexamethasone and rolipram were able to inhibit the early
      inflammatory response but were ineffective to limit the macrophage influx. In
      contrast, marimastat was able to reduce early and late response. These data
      indicate that MMP-12 instillation in mice could highlight some of the
      inflammatory response seen in COPD and could be used for the pharmacological
      evaluation of new anti-inflammatory mechanisms of action.

PMID- 17234181
TI  - Thiocolchicoside inhibits the activity of various subtypes of recombinant GABA(A)
      receptors expressed in Xenopus laevis oocytes.
AB  - Thiocolchicoside is a myorelaxant drug with anti-inflammatory and analgesic
      properties as well as pronounced convulsant activity. To characterize the
      mechanisms of action of this drug at the molecular level, we examined its effects
      on the function of various recombinant neurotransmitter receptors expressed in
      Xenopus oocytes. Electrophysiological recordings from recombinant human gamma
      aminobutyric acid type A (GABA(A)) receptors consisting of alpha1beta1gamma2L,
      alpha1beta2gamma2L, or alpha2beta2gamma2L subunit combinations revealed that
      thiocolchicoside inhibited GABA-evoked Cl(-) currents with similar potencies
      (median inhibitory concentrations of 0.13 to 0.2 microM) and in a competitive
      manner. Consistent with previous observations, thiocolchicoside also inhibited
      the binding of GABA to rat cerebral cortical membranes. Thiocolchicoside
      inhibited the function of recombinant human strychnine-sensitive glycine
      receptors composed of the alpha1 subunit with a potency (median inhibitory
      concentration of 47 microM) lower than that apparent with recombinant GABA(A)
      receptors. It also inhibited the function of human nicotinic acetylcholine
      receptors composed of the alpha4 and beta2 subunits, but this effect was only
      partial and apparent at high concentrations. In contrast, thiocolchicoside had no
      effect on the function of 5-HT(3A) serotonin receptors. Our results thus provide
      molecular evidence that the epileptogenic activity of thiocolchicoside might be
      due to inhibition of the function of inhibitory receptors in the central nervous
      system, especially that of GABA(A) receptors.

PMID- 17234182
TI  - Altered cell-cell adhesion in cisplatin-resistant human carcinoma cells: a link
      between beta-catenin/plakoglobin ratio and cisplatin resistance.
AB  - Acquired resistance to cisplatin represents a major obstacle to successful
      chemotherapy. We have developed cisplatin-resistant CA3(ST) and CK2 cells, which
      exhibited altered formation of cell-cell junctions compared to their parental
      cisplatin-sensitive human laryngeal carcinoma HEp-2 cells. Although cell-cell
      adhesion can induce antiapoptotic signaling, there is contradictory evidence
      considering the significance of cadherin-catenin complex in cellular response to
      cisplatin. Therefore, we analyzed junctional proteins in this model of cisplatin
      resistance. In both cisplatin-resistant sublines plakoglobin expression was
      decreased, while beta-catenin expression was increased, at cell-cell junctions.
      Although cisplatin-resistant cells showed decreased plakoglobin mRNA, they
      retained equal expression of beta-catenin mRNA as parental cells.
      Immunoprecipitation of cadherin-catenin complex established that upregulation of
      beta-catenin results from its stabilization through interaction with N-cadherin.
      Furthermore, beta-catenin upregulation was closely associated with cisplatin
      exposure, since cisplatin-resistant HeLa subline also had increased beta-catenin,
      while vincristine-resistant HEp-2 subline did not upregulate beta-catenin.
      However, single cisplatin treatment of HEp-2 cells did not induce beta-catenin
      upregulation, nor plakoglobin mRNA downregulation, suggesting that the alteration
      in catenin ratio is a late event, which requires repeated cisplatin exposure.
      Finally, we overexpressed plakoglobin in CA3(ST) cells and selected several
      clones that established the pattern of plakoglobin/beta-catenin expression found
      in HEp-2 cells. However, none of the clones restored sensitivity to cisplatin.
      Thus, it appears that beta-catenin and plakoglobin are not involved in the
      resistance development, implying that the observed alterations are an outcome of
      a slowly generating process, which is presumably a secondary event of vital
      cellular response triggered by cisplatin toxicity.

PMID- 17234183
TI  - TNF alpha promoter polymorphisms analysis in benign and malignant breast lesions.
AB  - Polymorphisms in genes involved in the complex mechanisms of carcinogenesis may
      affect the susceptibility to cancer. The multifunctional cytokine tumor necrosis
      factor alpha (TNF alpha) has an important role in the pathogenesis of
      inflammatory, autoimmune and malignant diseases. It has a large spectrum of
      activities, including both antitumorigenic and protumorigenic. In recent years,
      several TNF alpha promoter polymorphisms have been identified and related to the
      expression level of cytokine and to the susceptibility to solid tumors. The aim
      of our study was to investigate the frequency of three TNF alpha promoter
      polymorphisms (-1031, -308 and -238) in benign (fibrocystic changes) and
      malignant (invasive carcinoma) breast lesions. Using "real-time" PCR SNP analysis
      these polymorphisms were determined in 76 patients with benign and 158 patients
      with malignant breast lesions. The high expression genotypes at any of the three
      SNP polymorphisms were more frequent in invasive breast carcinoma (in 81 of 158
      examined, 51.3%) than in fibrocystic changes (in 33 of 76 examined, 43.4%). The
      combined frequency of high production genotypes (-1031 T/C and C/C, -308 G/A and
      A/A and -238 G/A and A/A) was higher in patients with invasive breast carcinoma
      than in those with fibrocystic changes. However, these results were not
      statistically significant. Further studies on a larger group of patients are
      needed to evaluate the significance of potential differences in TNF alpha
      genotypes in different breast lesions.

PMID- 17234184
TI  - Do first order and higher order regions of the thalamic reticular nucleus have
      different developmental timetables?
AB  - The thalamic reticular nucleus (TRN) can been subdivided into sectors based on
      thalamic and cortical input. Additionally, in carnivores the visual sector of the
      TRN can be subdivided into first order (perigeniculate nucleus: PGN) and higher
      order (TRN) regions. This report examines whether TRN development reflects the
      nature of its higher order visual connections. 170 cells from 12 kittens aged
      between postnatal day 0 (P0) and P125 were fully analysed after single cell
      injections in 400-500 microm fixed brain slices. TRN cells have a period of
      exuberant dendritic branching that peaks between P3 and P12, around the time of
      eye opening (P7), followed by branch pruning until P68. Similarly, most dendritic
      appendages are added between P12 and P22 followed by pruning, which is also
      largely complete by P68. Most branch points occur within the first 10-30% of the
      dendritic arbor, peaking between 10 and 20% (roughly equivalent to 100 mum from
      the soma), while appendages were concentrated between 20 and 30% of the arbour;
      appendages tend to be distributed over a larger proportion of the arbor up to P14
      compared to later ages. TRN and PGN maturation were not significantly different.
      The present data suggest that clear distinctions cannot be made between the
      maturation of first and higher order pathways and indicate that GABAergic cells
      of the ventral thalamus may mature earlier than relay cells of the dorsal
      thalamus. Furthermore, dendritic development in the TRN may be less dependent on
      extrinsic factors than an intrinsic growth pattern or factors other than a
      functional hierarchy within the visual pathway.

PMID- 17234185
TI  - IgG anti-GalNAc-GD1a antibody inhibits the voltage-dependent calcium channel
      currents in PC12 pheochromocytoma cells.
AB  - We investigated the effects of IgG anti-GalNAc-GD1a antibodies, produced by
      immunizing rabbits with GalNAc-GD1a, on the voltage-dependent calcium channel
      (VDCCs) currents in nerve growth factor (NGF)-differentiated PC12
      pheochromocytoma cells. VDCCs currents in NGF-differentiated PC12 cells were
      recorded using the whole-cell patch-clamp technique. Immunized rabbit serum that
      had a high titer of anti-GalNAc-GD1a antibodies inhibited the VDCCs currents in
      the NGF-differentiated PC12 cells (36.0+/-9.6% reduction). The inhibitory effect
      of this serum was reversed to some degree within 3-4 min by washing with bath
      solution. Similarly, application of purified IgG from rabbit serum immunized with
      GalNAc-GD1a significantly inhibited the VDCCs currents in PC12 cells (30.6+/-2.5%
      reduction), and this inhibition was recovered by washing with bath solution.
      Furthermore, the inhibitory effect was also observed in the GalNAc-GD1a affinity
      column binding fraction (reduction of 31.1+/-9.85%), while the GalNAc-GD1a
      affinity column pass-through fraction attenuated the inhibitory effect on VDCCs
      currents. Normal rabbit serum and normal rabbit IgG did not affect the VDCCs
      currents in the PC12 cells. In an immunocytochemical study using fluorescence
      staining, the PC12 cells were stained using GalNAc-GD1a binding fraction. These
      results indicate that anti-GalNAc-GD1a antibodies inhibit the VDCCs currents in
      NGF-differentiated PC12 cells.

PMID- 17234186
TI  - Acetylcholine release from fetal tissue homotopically grafted to the motoneuron
      depleted lumbar spinal cord. An in vivo microdialysis study in the awake rat.
AB  - Grafts of spinal cord (SC) tissue can survive and develop into the severed SC,
      but no conclusive data are available concerning the functional activity of
      transplanted neurons. In the present study, suspensions of prelabeled embryonic
      ventral SC tissue were grafted to the lumbar SC of rats with motoneuron loss
      induced by perinatal injection of volkensin. Eight to ten months post-grafting,
      acetylcholine (ACh) release was measured by microdialysis in awake rats, under
      either basal or stimulated conditions. In normal animals, baseline ACh output
      averaged 1.6 pmol/30 microl, it exhibited a 4-fold increase after KCl-induced
      depolarization or handling, and it was completely inhibited by tetrodotoxin
      administration. Moreover, ACh levels did not change following acute SC
      transection performed under anesthesia during ongoing dialysis, suggesting an
      intrinsic source for spinal ACh. Treatment with volkensin produced a severe
      (>85%) motoneuronal loss accompanied by a similar reduction in baseline ACh
      release and almost completely abolished effects of depolarization or handling. In
      transplanted animals, many motoneuron-like labeled cells were found within and
      just outside the graft area, but apparently in no case were they able to extend
      fibers towards the denervated muscle. However, the grafts restored baseline ACh
      output up to near-normal levels and responded with significantly increased
      release to depolarization, but not to handling. The present findings indicate
      that spinal neuroblasts can survive and develop within the motoneuron-depleted SC
      and release ACh in a near-normal, but apparently non-regulated, manner. This may
      be of importance for future studies involving intraspinal stem cell grafts.

PMID- 17234187
TI  - Differential neuroprotective effects of a minocycline-based drug cocktail in
      transient and permanent focal cerebral ischemia.
AB  - Considering that several pathways leading to cell death are activated in cerebral
      ischemia, we tested in mouse models of transient and permanent ischemia a drug
      cocktail aiming at distinct pharmacological targets during the evolution of
      ischemic injury. It consists of minocycline--an antibiotic with anti-inflammatory
      properties, riluzole--a glutamate antagonist, and nimodipine--a blocker of
      voltage-gated calcium channels. Administered 2 h after transient or permanent
      MCAO, it significantly decreased the size of infarction, by approximately 65%
      after transient and approximately 35% after permanent ischemia and markedly
      improve clinical recovery of mice. In both experimental models a three-drug
      cocktail achieved significantly more efficient neuroprotection than any of the
      components tested alone. However, some interesting observation emerged from the
      single-drug studies. Treatment with minocycline alone was efficient in both
      experimental models while treatment with glutamate antagonist riluzole conferred
      neuroprotection only after transient MCAO. Immunohistochemical analysis following
      three-drug treatment revealed reduced microglia/macrophages and caspase-3
      activation as well as preserved GFAP immunoreactivity following transient
      ischemia. No detectable differences in the levels of Mac-2, GFAP and caspase-3
      immunoreactivities were observed 72 h after permanent MCAO. These marked
      differences in the brain tissue responses to ischemic injury and to treatments
      suggest that different pathological mechanisms may be operating in transient and
      permanent ischemia. However, the three-drug cocktail exerted significant
      neuroprotection in both experimental models thus demonstrating that simultaneous
      targeting of several pathophysiological pathways involved in the evolution of
      ischemic injury may represent a rational therapeutic strategy for stroke.

PMID- 17234188
TI  - Role of Neu4L sialidase and its substrate ganglioside GD3 in neuronal apoptosis
      induced by catechol metabolites.
AB  - Mammalian sialidases are key enzymes in the degradation of glycoconjugates. Neu4L
      sialidase is localized to mitochondria and specifically expressed in brain. To
      elucidate the pathophysiological roles of Neu4L in the nervous system, we
      investigated the possible involvement of Neu4L in the apoptotic neurodegeneration
      under the existence of catechol metabolites generated by tyrosinase. We
      demonstrated that: (i) the expression level of Neu4L was dramatically decreased
      prior to apoptosis; (ii) the apoptotic phenotype was characterized by cytochrome
      c release into cytosol concomitant with the trafficking of ganglioside GD3 to
      mitochondria; and (iii) the inhibitor of glucosylceramide synthase partially
      recovered cell viability. Neu4L and its substrate GD3 may act as key molecules in
      the mitochondrial apoptotic pathway in neuronal cells.

PMID- 17234189
TI  - Lipolysis is altered in MHC class I zinc-alpha(2)-glycoprotein deficient mice.
AB  - Non-conventional major histocompatibility complex class I molecules are involved
      in a variety of physiological functions, most at the periphery of the immune
      system per se. Zinc-alpha(2)-glycoprotein (ZAG), the sole soluble member of this
      superfamily has been implicated in cachexia, a poorly understood yet life
      threatening, severe wasting syndrome. To further ascertain the role of ZAG in
      lipid metabolism and perhaps the immune system, we inactivated both ZAG alleles
      by gene targeting in mice. Subjecting these ZAG deficient animals to standard or
      lipid rich food regimens led to increased body weight in comparison to
      identically treated wild-type mice. This phenotype appeared to correlate with a
      significant decrease in adipocytic lipolysis that could not be rescued by several
      pharmacological agents including beta(3)-adrenoreceptor agonists. Furthermore, in
      contrast to previously reported data, ZAG was found to be ubiquitously and
      constitutively expressed, with an especially high level in the mouse liver. No
      overt immunological phenotype was identified in these animals.

PMID- 17234190
TI  - A complex peptide-sorting signal, but no mRNA signal, is required for the Sec
      independent transport of Ist2 from the yeast ER to the plasma membrane.
AB  - The yeast integral plasma membrane protein Ist2 belongs to a group of membrane
      proteins which are synthesized from localized mRNAs. The protein reaches the
      plasma membrane via the ER on a route operating independently of the classical
      secretory pathway. We have identified a complex peptide-sorting signal located at
      the extreme C-terminus. This sorting signal operates independently of targeting
      information in IST2 mRNA and sorting to the plasma membrane does not require She
      mediated mRNA transport into daughter cells. Based on these results, we suggest a
      posttranslational mechanism, which leads to the concentration of Ist2--via
      multimerization--at ER sites, followed by direct transport to the plasma
      membrane. This novel mechanism operates downstream of IST2 mRNA localization.

PMID- 17234191
TI  - Properties of extended predictive control.
AB  - Many tuning strategies for model predictive control algorithms have been proposed
      in the literature depending on the conditionality of the system matrix and the
      choice of its cost function. In this paper, the properties of a new predictive
      controller termed extended predictive control (EPC) are investigated and
      presented. These properties are important to the understanding of the unique
      tuning strategy of EPC. EPC is based on the assumption of infinite horizon which
      is preferable to guarantee stability. The EPC properties are derived using a
      second order plant with relatively large dead time and is applicable to any open
      loop stable system. The tuning strategy of EPC was applied to generalized
      predictive control with good results.

PMID- 17234192
TI  - Population genetic analysis of the ovine parasitic nematode Teladorsagia
      circumcincta and evidence for a cryptic species.
AB  - An understanding of genetic variation in parasite populations, and how it is
      partitioned, is required to underpin many areas of basic and applied research.
      Population genetic studies on parasitic nematode populations are still in their
      infancy and have been dominated by the use of single locus markers. We have used
      a panel of five microsatellite markers to undertake a genetic study of a number
      of field and laboratory populations of Teladorsagia circumcincta. High levels of
      polymorphism were seen in all the populations examined with the majority of
      diversity being within rather than between populations. There was no detectable
      genetic differentiation between the UK populations examined although they
      included both laboratory passaged and field isolates derived from different
      geographical regions and host species. This broadly supports previous mtDNA
      sequence diversity studies of this parasite in the UK and USA. However, some
      between-population genetic differentiation was apparent when several populations
      from French goats and a laboratory population from New Zealand were examined.
      Most notably, a population from a French goat farm, which has previously been
      suggested to contain a cryptic species, showed very high levels of genetic
      differentiation from all the other populations. Analysis of multi-locus genotypes
      suggested the presence of two sympatric parasite populations on this farm with
      little or no gene flow between them. This supports the hypothesis that parasites
      currently defined as T. circumcincta by routine morphological criteria comprise
      more than a single species.

PMID- 17234193
TI  - Receptors for the anaphylatoxins C3a and C5a are expressed in human
      atherosclerotic coronary plaques.
AB  - The anaphylatoxins C3a and C5a are potent chemotactic and pro-inflammatory
      peptides that are released during complement activation, and recent clinical work
      have suggested them a role in acute coronary events. Here we studied whether
      human coronary plaques express anaphylatoxin receptors C3aR and C5aR, i.e.
      whether they have the potential to respond to anaphylatoxins. For this purpose,
      both normal (n=14) and atherosclerotic (n=20) human coronary artery samples were
      collected for histological and PCR analyses. Immunohistochemistry demonstrated
      that in atherosclerotic, but not in normal intimas, C3aR and C5aR were present.
      Consistently, PCR analysis showed that the expression of both receptors was >5
      fold increased in the atherosclerotic plaques (p<0.01). Double immunofluorescence
      stainings revealed that in the plaques the principal cells expressing both C3aR
      and C5aR were macrophages. Moreover, T cells expressed C5aR and a small fraction
      of them also expressed C3aR, the mast cells expressed C5aR, whereas endothelial
      cells and subendothelial smooth muscle cells expressed both C3aR and C5aR. In
      conclusion, the presence of receptors for anaphylatoxins in human coronary
      plaques suggests that anaphylatoxins activate coronary plaques, and points the
      complement system as a potential therapeutic target in attempts to stabilize
      them.

PMID- 17234194
TI  - Increased circulating platelet-derived microparticles are associated with stent
      induced vascular inflammation.
AB  - Inflammation as well as platelet activation at the site of local vessel-wall
      injury plays an essential role in the mechanism of restenosis after Percutaneous
      coronary intervention (PCI). Platelet-derived microparticles (PDMPs) released
      from activated platelets are thought to play a role in the inflammatory process,
      possibly interacting with leukocyte integrin Mac-1. We serially measured
      circulating PDMPs, high-sensitive C-reactive protein (hs-CRP) and activated Mac-1
      on the surface of neutrophils in 61 patients undergoing coronary stenting. PDMPs,
      hs-CRP and Mac-1 increased after coronary stenting in a time-dependent manner
      with the maximum response at 48 h in coronary sinus blood (PDMPs: 10.3+/-8.9
      32.8+/-13.8 U/ml; P<0.001, hs-CRP: 0.27+/-0.23-1.46+/-0.99 mg/dl; P<0.001,
      activated Mac-1, 134+/-19% relative increase, P<0.001). PDMPs were correlated
      with hs-CRP (R=0.58, P<0.001) and the relative increase in Mac-1 (R=0.69,
      P<0.001) 48 h after coronary stenting. Multiple regression analysis showed that
      each of PDMPs (R=0.40, P<0.05), hs-CRP (R=0.33, P<0.05) and Mac-1 (R=0.48,
      P<0.01) was an independent predictor of the late lumen loss. Coronary stenting
      enhanced circulating PDMPs in association with an inflammatory response in the
      injured vessel wall. PDMPs may be a useful marker for evaluation of stent-induced
      inflammatory status and a powerful predictor of restenosis equivalent to
      activated Mac-1.

PMID- 17234195
TI  - Reduced atherosclerosis in chow-fed mice expressing high levels of a
      catalytically inactive human hepatic lipase.
AB  - Increased expression of catalytically inactive hepatic lipase (ciHL) lowers
      remnants and low-density lipoproteins (LDL) and may reduce atherosclerosis in
      mice lacking both LDLreceptors (LDLR) and murine (m) HL. However, in a previous
      study, ciHL expression failed to reduce atherosclerosis but increased liver fat
      accumulation after a 3-month high-fat diet, suggesting that diet-induced
      metabolic changes compromised the antiatherogenic effects of ciHL. Therefore, we
      hypothesized that reduced dietary fat would reduce atherosclerosis in ciHL
      expressing mice. Mice lacking both LDLR and mHL, alone, or expressing ciHL were
      fed a low-fat (chow) diet for 9 months to match the cumulative cholesterol
      exposure resulting from a 3-month high-fat diet. Plasma lipids and lipoproteins
      as well as atherosclerosis were determined at sacrifice. Also, liver expression
      of receptors and proteins contributing to cholesterol delivery including the
      LDLreceptor related protein (LRP), scavenger receptor (SR)-B1 and apoE were
      determined. At 9 months, ciHL expression reduced plasma cholesterol by
      approximately 20% and atherosclerosis by 79% (from 2.67+/-0.61% of aortic
      surface, Ldlr-/-hl-/-, n=9, to 0.55+/-0.32% of aortic surface, Ldlr-/-hl-/-ciHL,
      n=7, P=0.01). Also, LRP-expression increased approximately 4-fold, whereas SR-B1
      and apoE remained unchanged. These results demonstrate that ciHL expression
      reduces atherosclerosis. Also, these results demonstrate that ciHL increases LRP
      expression and suggest increased LRP-mediated lipoprotein clearance as a pathway
      for ciHL-mediated atherosclerosis reduction.

PMID- 17234196
TI  - Preparation and characterisation of ribonuclease monolithic bioreactor.
AB  - In gene therapy and DNA vaccination, RNA removal from DNA preparations is vital
      and is typically achieved by the addition of ribonuclease into the sample.
      Removal of ribonuclease from DNA samples requires an additional purification
      step. An alternative is the implementation of immobilized ribonuclease. In our
      work, ribonuclease was covalently coupled onto the surface of methacrylate
      monoliths via epoxy or imidazole carbamate groups. Various immobilization
      conditions were tested by changing immobilization pH. Ribonuclease immobilized on
      the monolith via imidazole carbamate groups at pH 9 was found to be six times
      more active than the ribonuclease immobilized on the monolith via epoxy groups.
      Under optimal immobilization conditions the Michaelis-Menten constant, Km, for
      cytidine-2,3-cyclic monophosphate, and turnover number, k3 were 0.52 mM and 4.6s(
      1), respectively, and mirrored properties of free enzyme. Enzyme reactor was
      found to efficiently eliminate RNA contaminants from DNA samples. It was active
      for several weeks of operation and processed 300 column volumes of sample.
      Required residence time to eliminate RNA was estimated to be around 0.5 min
      enabling flow rates above 1 column volume per min.

PMID- 17234197
TI  - Determination of biotin following derivatization with 2-nitrophenylhydrazine by
      high-performance liquid chromatography with on-line UV detection and electrospray
      ionization mass spectrometry.
AB  - Currently, biotin is typically determined in Japan using a microbiological
      method. Such microbiological assays are sensitive, but they are not always highly
      specific and are also rather tedious and time-consuming. In the present study, RP
      HPLC and LC-MS methods for the determination of biotin have been developed by
      derivatizing the carboxyl group with 2-nitrophenylhydrazine hydrochloride. 2
      Nitrophenylhydrazine is used for the derivatization of carboxylic acids, and
      these derivatives are known to be applicable to LC-MS detection. Biotin in
      tablets were extracted by the addition of water and ultrasonic agitation. In
      order to clean up the sample solution, the filtrate was applied to an ODS
      cartridge and eluted with methanol. The conditions for preparing the 2
      nitrophenylhydrazide derivatives were modified from a previous report for fatty
      acids. Good recovery rates of over 70% were obtained for the addition of 5-125
      microg of biotin per formulation. The detection limit in HPLC at 400 nm was 0.6
      ng per injection, with good linearity being obtained over the concentration range
      0.001-0.2 microg per injection. Further, derivatives were determined by LC-MS
      with electrospray ionization, where the spectra indicated the molecular ions
      [M+H](+). The detection limit was 0.025 ng per injection in the selected ion
      monitoring analysis, and linearity was observed in the range of 0.6-6 ng per
      injection. The proposed method could be used to specifically determine the
      presence of biotin in relatively clean samples.

PMID- 17234198
TI  - Simultaneous determination of multi-component mycotoxin contaminants in foods and
      feeds by ultra-performance liquid chromatography tandem mass spectrometry.
AB  - The present study developed an improved analytical method for the simultaneous
      quantification of 17 kinds of Aspergillus, Fusarium and Penicillium mycotoxin
      contaminants in foods and feeds by ultra-performance liquid chromatography
      combined with electrospray ionization triple quadrupole tandem mass spectrometry
      (UPLC-MS/MS) under the multiple reaction monitoring (MRM) mode, and especially
      focused on the optimization of extraction, clean-up, UPLC separation and MS/MS
      parameters of analytes. Homogenized samples were sequentially extracted by 84%
      (v/v) of acetonitrile aqueous solution with the selected internal standard
      (zearalanone) spiking, SPE clean-up with Mycosep 226 Aflazon+ Multifunctional
      cartridges, filtration, concentration and secondary filtration. Using double
      sample injection method, the analytes were separated by UPLC BEH C18 column (100
      mm x 2.1 mm I.D., 1.7 microm), and eluted with ammonium acetate/methanol and
      aqueous ammonia/methanol for the ESI+ and ESI- analysis, respectively. The 10
      positive ions and 7 negative ions of mycotoxins were separated by gradient
      elution with the retention time of 6.5 and 4 min, respectively. The LOQ of
      selected analytes ranged from 0.01 to 0.70 microg kg(-1), which was lower than
      the criteria of EU, USA and other countries on the determination of the minimum
      limiting level of various mycotoxins in foods including baby foods and feed
      stuffs. Meanwhile, high correlation coefficients (r2>0.99) of 17 mycotoxins were
      obtained within their respective linear ranges (0.05-20 microg kg(-1) for 10
      positive ions and 0.5-50 microg kg(-1) for 7 negative ions) and reasonable
      recoveries (70.6-119.0%) of them were also demonstrated in different spiked
      levels. This quantitative method has many advantages including simple
      pretreatment, rapid determination and high sensitivity, which could be applied to
      the determination and quantification of multi-component mycotoxin contaminants in
      complex matrixes. Meanwhile, the method successfully fulfilled the minimum
      limiting level requests from various countries.

PMID- 17234199
TI  - Analysis of magnolol and honokiol in biological fluids by capillary zone
      electrophoresis.
AB  - Capillary zone electrophoresis (CZE) method was used for analysis of magnolol and
      honokiol. Under the optimized condition, CZE with UV absorption detection
      provided that the limit of detection was at microM level. To enhance detection
      sensitivity of magnolol and honokiol, CZE separation system was coupled with a
      laser-induced fluorescence (LIF) detector for the first time. The limits of
      detection of magnolol and honokiol were 12 nM (3.20 ng ml(-1)) and 18 nM (4.79 ng
      ml(-1)), respectively, showing that the CZE-LIF system provides greater than 100
      fold sensitivity improvements than does the CZE-UV system. The developed method
      was applied to analyze magnolol and honokiol in spiked human plasma samples,
      microsome incubation samples as a preliminary demonstration of its potential in
      pharmacokinetic studies.

PMID- 17234200
TI  - Alternative sample preparation method for photochemical studies based on solid
      phase microextraction: synthetic pyrethroid photochemistry.
AB  - An alternative sample preparation method for photochemical studies, which
      overcomes all the disadvantages associated with classical approaches, is
      proposed. The method is based on Solid Phase Microextraction (SPME) and can be
      considered as being within the scope of "green photochemistry", especially when
      it is combined with sunlight irradiation. To demonstrate the potential of the
      procedure, photochemical studies of synthetic pyrethroids were carried out.
      Photodegradation pathways for five dihalogenovinyl-substituted pyrethroid
      pesticides: permethrin, deltamethrin, cyfluthrin, cypermethrin and lambda
      cyhalothrin, are proposed, and kinetic curves and parameters provided. This
      information, obtained by rapidly carried out, green experiments, allows us to
      corroborate photoproducts reported by other authors and to identify the
      photoproducts proposed for the first time in the present study.

PMID- 17234201
TI  - Observation of characteristic IR band assignable to dimerized copper ions in
      montmorillonite.
AB  - Copper ion-exchanged montmorillonite clays, which had been prepared by ion
      exchange in an aqueous solution of CuCl(2) at a temperature above 323 K,
      exhibited the characteristic IR band in the region 3360-3310 cm(-1). No such
      bands were observed for the samples prepared by using different ion-exchange
      solutions and at different temperatures. From the spectroscopic observations, it
      was revealed that the ion-exchanged copper ions (Cu(2+)) are in the form of
      dimerized species by bridging two hydroxyls, [Cu(2+) <(OH(-)(2) > Cu(2+)], in
      montmorillonite.

PMID- 17234202
TI  - Compression and shear surface rheology in spread layers of beta-casein and beta
      lactoglobulin.
AB  - We investigate the surface viscoelasticity of beta-lactoglobulin and beta-casein
      spread surface monolayers using a recently discovered method. Step compressions
      are performed, and the surface pressure is measured as a function of time. This
      is a common experiment for surface monolayers. However in our experiments the
      pressure is recorded by two perpendicular sensors, parallel and perpendicular to
      the compression direction. This enables us to clearly measure the time relaxation
      of both the compression and shear moduli, at the same time, in a single
      experiment, and with a standard apparatus. beta-Lactoglobulin and beta-casein
      monolayers are interesting because of their importance in food science and
      because they exhibit universally slow dynamical behavior that is still not fully
      understood. Our results confirm that the compressional modulus dominates the
      total viscoelastic response in both proteins. Indeed for beta-casein we confirm
      that the shear modulus is always negligible, i.e., the layer is in a fluid state.
      In beta-lactoglobulin a finite shear modulus emerges above a critical
      concentration. We emphasize that in Langmuir trough dynamic experiments the
      surface pressure should be measured in both the compression and the perpendicular
      directions.

PMID- 17234203
TI  - Three minimum wet thickness regions of slot die coating.
AB  - An experimental study was carried out to determine the minimum wet thickness of
      slot die coating for low-viscosity solutions. There exist three distinct coating
      regions (I, II, and III), depending on the physical properties of the coating
      fluid, die geometry, and flow conditions. A critical Reynolds number was found,
      below which viscous and surface tension effects are important. In Region I, the
      minimum wet thickness increases with increasing capillary number and becomes
      independent of capillary number in Region II. Region III exists above the
      critical Reynolds number where fluid inertia is dominant. In this region, the
      minimum wet thickness decreases as Reynolds number increases. Flow visualization
      on the coating bead reveals that the position of the downstream meniscus of the
      coating bead determines the types of coating region, whereas the shape and
      position of the upstream meniscus determine the type of coating defects. It was
      also observed that the downstream meniscus was not located at the die lip corner
      and both the static and dynamic contact angles varied under different conditions.
      These findings are critical for realistic theoretical study of slot die coating.

PMID- 17234204
TI  - Transport of wetting liquid plugs in bifurcating microfluidic channels.
AB  - A plug of wetting liquid is driven at constant pressure through a bifurcation in
      a microchannel. For a plug advancing in a straight channel, we find that the
      viscous dissipation in the bulk may be estimated using Poiseuille's law while
      Bretherton and Tanner's laws model the additional dissipation occurring at the
      rear and front interfaces. At a second stage, we focus on the behavior of the
      plug flowing through a T-junction. Experiments show the existence of a threshold
      pressure, below which the plug remains blocked at the entrance of the junction.
      Above this required pressure, the plug enters the bifurcation and either ruptures
      or splits into two daughter plugs, depending on the applied pressure and on the
      initial length of the plug. By means of geometrical arguments and the previously
      cited laws, we propose a global model to predict the transitions between the
      three observed behaviors.

PMID- 17234205
TI  - The influence of developmental stage on cold shock resistance and ability to cold
      harden in Drosophila melanogaster.
AB  - Thermal sensitivity and ability to rapidly cold- and heat-harden may change
      during ontogeny. This study reports how inherent cold tolerance and ability to
      rapidly cold-harden change across eight developmental stages in both genders of
      Drosophila melanogaster using a similar experimental approach for all stages.
      Inherent cold tolerance was estimated as LT50 by assaying cold shock survival
      over a wide range of temperatures (-16 to 5 degrees C). Rapid cold-hardening
      (RCH) was applied by cooling from 25 to 0 degrees C at -0.25 degrees C min(-1)
      followed by 1 h at 0 degrees C. Individuals were cold shocked either directly or
      after RCH to estimate the effect of RCH. We found large variation in cold
      tolerance among developmental stages and minor differences between genders. Eggs
      were most tolerant followed by adults, pupae and larvae. In the light of this and
      other studies it is suggested that there is a general pattern of stage specific
      thermal stress resistance in Drosophila. The capacity to rapidly cold-harden was
      found in both sexes of larval, pupal and adult stages, though some developmental
      stages showed negative or neutral effects of RCH which was probably due to the
      cost associated with the hardening treatment in these cold susceptible stages.
      The early presence of RCH indicates that the mechanisms behind hardening are not
      stage specific and that RCH may be an ecologically important trait in early
      stages of ontogeny.

PMID- 17234206
TI  - Age and hypertrophy alter the contribution of sarcoplasmic reticulum and Na+/Ca2+
      exchange to Ca2+ removal in rat left ventricular myocytes.
AB  - Age and hypertension contribute significantly to cardiac morbidity and mortality,
      however the importance of each during the progression of hypertrophy is unclear.
      This investigation examined the effect of age and hypertension on Ca(2+) handling
      in rat ventricular myocytes by comparing a genetic model of hypertension and
      cardiac hypertrophy (spontaneously hypertensive rat, SHR) with its normotensive
      control (Wistar-Kyoto rat, WKY) at 5 and 8 months of age. Experiments were
      performed on single left ventricular myocytes isolated from SHR or WKY hearts.
      Intracellular Ca(2+) was measured optically using fura-2 or fluo-3. SHR myocytes
      had a significantly larger cell width and volume and a significantly decreased
      cell length/width ratio at 5 and 8 months compared to normotensive controls. Age
      had no effect on cell length, width, volume or the length/width ratio. Ca(2+)
      transient amplitude, sarcoplasmic reticulum (SR) Ca(2+) content and contraction
      amplitude were unaffected by age or hypertrophy. However at 8 months the
      contribution of the SR to Ca(2+) uptake during relaxation decreased, with a
      concomitant increase in the contribution of Na(+)/Ca(2+) exchanger (NCX) function
      to relaxation, in SHR and WKY myocytes. The incidence of non-synchronous SR
      Ca(2+) release decreased with age but not hypertrophy in SHR and WKY myocytes.
      These results show that the changes in Ca(2+) handling observed during
      progression of mild hypertrophy in SHR are the same as those that occur during
      ageing in normotensive control animals and can, therefore, be ascribed to
      maturation rather than hypertrophy.

PMID- 17234207
TI  - The development of cardiac fibrosis in low tissue factor mice is gender-dependent
      and is associated with differential regulation of urokinase plasminogen
      activator.
AB  - Tissue factor (TF) initiates the protease coagulation cascade in response to
      tissue injury. Homozygous deficiency of murine TF results in embryonic lethality,
      which is rescued by low-level expression of human TF. These low-TF mice have been
      shown to develop cardiac fibrosis. We tested the hypothesis that the development
      of cardiac fibrosis in low-TF mice results from dysregulated protease expression
      and is affected by gender. Mice were divided into the age groups 2-5, 6-12, 13-18
      and 19+ weeks. Fibrosis was assessed by trichrome staining. Protease expression
      was measured in male and female mice by RT-PCR for mRNA and zymography, ELISA or
      immunoblot for protein. Urokinase plasminogen activator (uPA) activity was
      determined by zymography and chromogenic substrate assay. A marked gender effect
      was noted for the development of fibrosis, with interstitial collagen deposition
      occurring from 9 weeks in male low-TF mice, but not until 19 weeks in low-TF
      females. This delayed onset in females was accompanied by delayed up-regulation
      of molecular markers of injury. Matrix metalloproteinase (MMP)-3 and tissue
      inhibitor of metalloproteinase (TIMP)-1 expression were up-regulated in the
      hearts of male low-TF mice from 6 to 12 weeks and in females from 19 weeks.
      MMP/TIMP dysregulation was not seen prior to cardiac fibrosis and did not appear
      to explain the gender differences. However, uPA expression and activity were down
      regulated prior to cardiac fibrosis in low-TF females, but were up-regulated in
      age-matched males. This suggests that the down-regulation of uPA in female low-TF
      mice protects them from more severe cardiac fibrosis.

PMID- 17234208
TI  - S-nitrosylated and pegylated hemoglobin, a newly developed artificial oxygen
      carrier, exerts cardioprotection against ischemic hearts.
AB  - Cell-free hemoglobin (Hb) derivatives that have been developed as Hb-based
      artificial oxygen carrier cause both coronary vasoconstriction and platelet
      aggregation due to the scavenging actions of nitric oxide (NO). Recently, native
      Hb is found to undergo S-nitrosylation, which regulates blood flow, whereas
      artificial oxygen carriers are lacking of S-nitrosylation. Therefore, S
      nitrosylated and pegylated hemoglobin (SNO-PEG-Hb) was prepared to overcome the
      above defects, where pegylation was included to avoid extravasation and to
      prolong the circulatory half-live. Since SNO-PEG-Hb possesses SNO property, we
      tested whether SNO-PEG-Hb increases coronary blood flow (CBF) and improves the
      severity of myocardial ischemia. In 19 open chest dogs, the left anterior
      descending coronary artery was perfused with blood from the carotid artery via
      the bypass tube, and then CBF and coronary perfusion pressure (CPP) were
      measured. After hemodynamic stabilization, CPP was reduced so that CBF decreased
      to 33% of the baseline and thereafter CPP was maintained constant. Ten minutes
      after the onset of coronary hypoperfusion, we infused 10% SNO-PEG-Hb into the
      coronary artery (2.5 ml/min). SNO-PEG-Hb increased CBF (28.1+/-3.3 to 43.3+/-3.9
      ml/100 g/min, p<0.05), fractional shortening (4.6+/-1.2 to 16.6+/-2.4%, p<0.01)
      and lactate extraction ratio (-38.5+/-8.6 to 25.5+/-1.3%, p<0.01). Thus, we
      conclude that SNO-PEG-Hb increases coronary blood flow and improves the
      contractile and metabolic dysfunction of the ischemic myocardium. SNO-PEG-Hb, a
      newly developed artificial oxygen carrier, may mediate a cardioprotection in
      ischemic heart diseases in addition to blood supplementation.

PMID- 17234209
TI  - The structure of a bacterial L-amino acid oxidase from Rhodococcus opacus gives
      new evidence for the hydride mechanism for dehydrogenation.
AB  - l-Amino acid oxidase from Rhodococcus opacus (roLAAO) is classified as a member
      of the GR(2)-family of flavin-dependent oxidoreductases according to a highly
      conserved sequence motif for the cofactor binding. The monomer of the homodimeric
      enzyme consists of three well-defined domains: the FAD-binding domain
      corresponding to a general topology throughout the whole GR(2)-family; a
      substrate-binding domain with almost the same topology as the snake venom LAAO
      and a helical domain exclusively responsible for the unusual dimerisation mode of
      the enzyme and not found in other members of the family so far. We describe here
      high-resolution structures of the binary complex of protein and cofactor as well
      as the ternary complexes of protein, cofactor and ligands. This structures in
      addition to the structural knowledge of snake venom LAAO and DAAO from yeast and
      pig kidney permit more insight into different steps in the reaction mechanism of
      this class of enzymes. There is strong evidence for hydride transfer as the
      mechanism of dehydrogenation. This mechanism appears to be uncommon in a sense
      that the chemical transformation can proceed efficiently without the involvement
      of amino acid functional groups. Most groups present at the active site are
      involved in substrate recognition, binding and fixation, i.e. they direct the
      trajectory of the interacting orbitals. In this mode of catalysis orbital
      steering/interactions are the predominant factors for the chemical step(s). A
      mirror-symmetrical relationship between the two substrate-binding sites of d and
      l-amino acid oxidases is observed which facilitates enantiomeric selectivity
      while preserving a common arrangement of the residues in the active site. These
      results are of general relevance for the mechanism of flavoproteins and lead to
      the proposal of a common dehydrogenation step in the mechanism for l and d-amino
      acid oxidases.

PMID- 17234210
TI  - The crystal structure of C2a, the catalytic fragment of classical pathway C3 and
      C5 convertase of human complement.
AB  - The multi-domain serine protease C2 provides the catalytic activity for the C3
      and C5- convertases of the classical and lectin pathways of complement
      activation. Formation of these convertases requires the Mg(2+)-dependent binding
      of C2 to C4b, and the subsequent cleavage of C2 by C1s or MASP2, respectively.
      The C-terminal fragment C2a consisting of a serine protease (SP) and a von
      Willebrand factor type A (vWFA) domain, remains attached to C4b, forming the C3
      convertase, C4b2a. Here, we present the crystal structure of Mg(2+)-bound C2a to
      1.9 A resolution in comparison to its homolog Bb, the catalytic subunit of the
      alternative pathway C3 convertase, C3bBb. Although the overall domain arrangement
      of C2a is similar to Bb, there are certain structural differences. Unexpectedly,
      the conformation of the metal ion-dependent adhesion site and the position of the
      alpha7 helix of the vWFA domain indicate a co-factor-bound or open conformation.
      The active site of the SP domain is in a zymogen-like inactive conformation. On
      the basis of these structural features, we suggest a model for the initial steps
      of C3 convertase assembly.

PMID- 17234211
TI  - Recognition and cooperation between the ATP-dependent RNA helicase RhlB and
      ribonuclease RNase E.
AB  - The Escherichia coli protein RhlB is an ATP-dependent motor that unfolds
      structured RNA for destruction by partner ribonucleases. In E. coli, and probably
      many other related gamma-proteobacteria, RhlB associates with the essential
      endoribonuclease RNase E as part of the multi-enzyme RNA degradosome assembly.
      The interaction with RNase E boosts RhlB's ATPase activity by an order of
      magnitude. Here, we examine the origins and implications of this effect. The
      location of the interaction sites on both RNase E and RhlB are refined and
      analysed using limited protease digestion, domain cross-linking and homology
      modelling. These data indicate that RhlB's carboxy-terminal RecA-like domain
      engages a segment of RNase E that is no greater than 64 residues. The interaction
      between RhlB and RNase E has two important consequences: first, the interaction
      itself stimulates the unwinding and ATPase activities of RhlB; second, RhlB gains
      proximity to two RNA-binding sites on RNase E, with which it cooperates to unwind
      RNA. Our homology model identifies a pattern of residues in RhlB that may be key
      for recognition of RNase E and which may communicate the activating effects. Our
      data also suggest that the association with RNase E may partially repress the RNA
      binding activity of RhlB. This repression may in fact permit the interplay of the
      helicase and adjacent RNA binding segments as part of a process that steers
      substrates to either processing or destruction, depending on context, within the
      RNA degradosome assembly.

PMID- 17234212
TI  - Structural analysis of cassiicolin, a host-selective protein toxin from
      Corynespora cassiicola.
AB  - Cassiicolin is a host-selective toxin (HST) produced by the fungus Corynespora
      cassiicola (strain CCP). It is responsible for the Corynespora leaf fall (CLF)
      disease, which is among the main pathologies affecting rubber tree (Hevea
      brasiliensis). Working on purified cassiicolin and using electron microscopy, we
      have demonstrated that this 27-residue O-glycosylated protein is able to induce
      cellular damages identical to those induced by the fungus on rubber tree leaves
      and displays the same host selectivity. The solution structure and disulfide
      pairing of cassiicolin have been determined using NMR spectroscopy and simulated
      annealing calculations. Cassiicolin appears to have an original structure with a
      prolate ellipsoid shape. It adopts an over-all fold consisting of three strands
      arranged in a right-handed twisted, antiparallel beta-sheet knitted by three
      disulfide bonds. Its conformation resembles that found in small trypsine-like
      inhibitors isolated from the brain, the fat body and the hemolymph of locust
      grasshoppers. But cassiicolin has no sequence homology with these protease
      inhibitors, and lacks their characteristic substrate-binding loop. Probably, this
      motif represents one of the few highly stabilized "minimal" scaffolds, with a
      high sequence permissiveness, that nature has selected to evolve over different
      phyla and to support different functions. The knowledge of the 3D structure opens
      the way to the delineation of the mechanism of action of the toxin using site
      directed mutagenesis.

PMID- 17234213
TI  - Pilot case study of the therapeutic potential of hyperbaric oxygen therapy on
      chronic brain injury.
AB  - BACKGROUND: Recently, the effect of hyperbaric oxygen (HBO(2)) therapy was
      explored in the treatment of chronic TBI. It has been speculated that idling
      neurons in the penumbra zone remain viable several years after injury and might
      be reactivated by enhanced oxygenation. We studied the therapeutic potential of
      HBO(2) therapy in a 54-year-old man who had sustained traumatic brain injuries
      one year before testing that resulted in permanent neurological symptoms.
      METHODS: Two treatment series separated by a one-year inter-session interval were
      administered. Treatment series consisted of 20 and 60 daily one-hour exposures to
      100% oxygen at 2 ATA. Electrophysiological (event-related potentials), metabolic
      and behavioral (sensorimotor and neuropsychological) measurements were obtained
      to evaluate the effects of hyperbaric oxygen therapy on neurocognitive
      functioning. RESULTS: Following the initial treatment, the patient showed
      improvements in sensorimotor functions, as well as enhanced P300 amplitude in the
      damaged hemisphere. Although most of these gains were no longer observed one year
      after treatment, these were reinstated with an additional series of 60 exposures.
      Neuropsychological improvements were also observed after the completion of the
      second series of treatments. CONCLUSION: The present single-case study provides
      preliminary evidence of neuropsychological and electrophysiological improvements
      after series of 20 and 60 treatments, although the first dosage appeared to be
      insufficient to produce permanent benefits. Longitudinal studies using different
      treatment parameters should be conducted if we are to systematically investigate
      long-term improvements resulting from HBO(2) therapy.

PMID- 17234214
TI  - Absence of Mycoplasma-specific DNA sequence in brain, blood and CSF of patients
      with multiple sclerosis (MS): a study by PCR and real-time PCR.
AB  - Mycoplasmas are the smallest of the known self-replicating organisms. They lack
      cell walls and are associated with numerous diseases in humans and animals. We
      are exploring the possibility that infection by Mycoplasma may induce the
      inflammatory demyelinating disease of the central nervous system (CNS) that is
      MS. The presence of specific Mycoplasma species DNA was sought in brain, serum
      and cerebrospinal fluid (CSF) of patients diagnosed with multiple sclerosis (MS)
      and other neurological diseases (OND) including inflammatory disorders. The MS
      samples from patients with active and progressive MS, as well as in remission, a
      variety of other neurological disease controls, including inflammatory CNS
      diseases such as meningitis, cryptococcal meningitis and encephalitis and other
      neurological disorders such as migraine were also examined. Clinical samples were
      provided by the National Neurological Research Specimen Bank and the Human Brain
      and Spinal Fluid Resource Centre, Los Angeles. Analysis was carried out by
      conventional PCR using Mycoplasma-specific primers (McAuliffe et al., 2005) that
      target the 16S rDNA gene in Mycoplasma species. The Mycoplasma-specific primers
      could detect 102 Mycoplasma species. In this study, 30 samples of human brain and
      57 pairs of serum and CSF and were examined. No Mycoplasma-specific nucleic acid
      sequence was detected, and the consistent observation of an endogenous gene,
      human serum albumin (HSA), as a positive control documented the adequacy of the
      method. Real-time PCR analysis of serum and CSF was done also targeting utilizing
      the Mycoplasma 16S rDNA gene, and this also demonstrated the lack of Mycoplasma
      in these samples. The presence of Mycoplasma at extraneural sites in MS patients
      is now being explored.

PMID- 17234215
TI  - Supranuclear vertical gaze abnormalities in sporadic Creutzfeldt-Jakob disease.
AB  - Supranuclear gaze palsies are an uncommon feature of Creutzfeldt-Jakob disease
      (CJD). Most reported cases of CJD with features of supranuclear gaze palsy are
      familial. We report 2 patients with supranuclear vertical gaze abnormalities
      associated with spongiform changes in the midbrain. Both patients were found to
      have sporadic CJD after genetic testing. Distinguishing familial from sporadic
      CJD in this setting has important genetic and epidemiological implications.

PMID- 17234216
TI  - Quasi-steady-state kinetics at enzyme and substrate concentrations in excess of
      the Michaelis-Menten constant.
AB  - In vitro enzyme reactions are traditionally conducted under conditions of
      pronounced substrate excess since this guarantees that the bound enzyme is at
      quasi-steady-state (QSS) with respect to the free substrate, thereby justifying
      the Briggs-Haldane approximation (BHA). In contrast, intracellular reactions,
      amplification assays, allergen digestion assays and industrial applications span
      a range of enzyme-to-substrate ratios for which the BHA is invalid, including the
      extreme of enzyme excess. The quasi-equilibrium approximation (QEA) is valid for
      a subset of enzyme excess states. Previously, we showed that the total QSSA
      (tQSSA) overlaps and extends the validity of the BHA and the QEA, and that it is
      at least roughly valid for any total substrate and enzyme concentrations. The
      analysis of the tQSSA is hampered by square root nonlinearity. Previous
      simplifications of the tQSSA rate law are valid in a parameter domain that
      overlaps the validity domains of the BHA and the QEA and only slightly extends
      them. We now integrate the tQSSA rate equation in closed form, without resorting
      to further approximations. Moreover, we introduce a complimentary simplification
      of the tQSSA rate law that is valid in states of enzyme excess when the absolute
      difference between total enzyme and substrate concentrations greatly exceeds the
      Michaelis-Menten constant. This includes a wide range of enzyme and substrate
      concentrations where both the BHA and the QEA are invalid and allows us to define
      precisely the conditions for zero-order and first-order product formation.
      Remarkably, analytical approximations provided by the tQSSA closely match the
      expected stochastic kinetics for as few as 15 reactant molecules, suggesting that
      the conditions for the validity of the tQSSA and for its various simplifications
      are also of relevance at low molecule numbers.

PMID- 17234217
TI  - Antihyperglycemic effect of a new thiazolidinedione analogue and its role in
      ameliorating oxidative stress in alloxan-induced diabetic rats.
AB  - Thiazolidinediones (TZDs) are a new class of antidiabetic drugs, having an
      insulin sensitizing effect in patients with type 2 diabetes. The contribution of
      oxidative stress from the standpoint of lipid and protein damage, alteration in
      endogenous antioxidant enzymes and effects of newly synthesized compounds, 5-[4-2
      (6,7-Dimethyl-1,2,3,4-tetrahydro-2-oxo-4
      quinoxalinyl)ethoxy]phenyl]methylene]thiazolid- ine-2,4-dione, (C(1)) in
      normal/alloxan-induced diabetic rats form the focus area of this study. Its
      effect was compared to two well-known TZDs, namely pioglitazone and
      rosiglitazone. It has been concluded from results that after thirty days of
      administration of C(1), Pg and Rg in alloxan-induced diabetic animal groups, the
      blood glucose level decreased, more remarkably in C(1) treated group. Also
      oxidative damage has been studied by estimating hepatic superoxide dismutase
      (SOD) activity, which was found to be increased (p<0.001 vs. control). An inverse
      change in SOD values between hepatic and pancreatic/kidney tissues were observed.
      Treatment with the test compounds lowered the activity of SOD in liver while
      increased its activity in kidney and pancreas. Similar normalizing effect of C(1)
      on liver, pancreatic and renal catalase (CAT)/ glutathione peroxidase (GPx)
      activities were pronounced in diabetic rats (p<0.001 vs. diabetic rats).
      Decreased reduced glutathione (GSH) content, found in diabetic animals, was
      significantly elevated to normal levels by C(1) treatment. The treatment with
      C(1) also decreased the levels of nitric oxide and increased the activities of
      glutathione-s-transferase and glutathione reductase, as compared to diabetic
      animals. Evidence of oxidative damage to lipids and proteins was shown through
      the quantification of protein carbonyl (in tissues) and malondialdehyde levels
      (both serum and tissues). It was observed that the protein/lipid damage in
      diabetic rats was improved by treatment with C(1). Total antioxidant activity
      (TAA) was found to be enhanced in C(1) treated rats (p>0.05 vs. group3, p<0.001
      vs. group2, p<0.001 vs. group 4). These results suggest that the newly
      synthesized TZD derivative (C(1)) has a potential to act as antihyperglycemic and
      antioxidant agent. In addition, for all parameters checked, it has better
      efficacy than rosiglitazone and is as effective as pioglitazone.

PMID- 17234218
TI  - Imitation and action understanding in autistic spectrum disorders: how valid is
      the hypothesis of a deficit in the mirror neuron system?
AB  - The motor mirror neuron system supports imitation and goal understanding in
      typical adults. Recently, it has been proposed that a deficit in this mirror
      neuron system might contribute to poor imitation performance in children with
      autistic spectrum disorders (ASD) and might be a cause of poor social abilities
      in these children. We aimed to test this hypothesis by examining the performance
      of 25 children with ASD and 31 typical children of the same verbal mental age on
      four action representation tasks and a theory of mind battery. Both typical and
      autistic children had the same tendency to imitate an adult's goals, to imitate
      in a mirror fashion and to imitate grasps in a motor planning task. Children with
      ASD showed superior performance on a gesture recognition task. These imitation
      and gesture recognition tasks all rely on the mirror neuron system in typical
      adults, but performance was not impaired in children with ASD. In contrast, the
      ASD group were impaired on the theory of mind tasks. These results provide clear
      evidence against a general imitation impairment and a global mirror neuron system
      deficit in children with autism. We suggest this data can best be understood in
      terms of multiple brain systems for different types of imitation and action
      understanding, and that the ability to understand and imitate the goals of hand
      actions is intact in children with ASD.

PMID- 17234219
TI  - Effects of ventrolateral striatal inactivation on predatory hunting.
AB  - Previous studies from our laboratory have shown that insect hunting is associated
      with a distinct Fos up-regulation in the ventrolateral caudoputamen at
      intermediate rostro-caudal levels. It is largely known that ventrolateral
      striatum participates in the control of orofacial movements and forepaw usage
      accompanying feeding behavior, but there has been no study investigating its
      possible roles during predatory hunting. We have presently examined the role of
      the ventrolateral striatum during roach hunting by using the reversible blockade
      with lidocaine. Accordingly, non-treated and saline-treated animals performed the
      insect hunting quite well, displaying a rather stereotyped form of motor actions
      for chasing, capturing and killing the prey. During the bilateral blockade of the
      ventrolateral striatum, the animals showed a significantly longer latency to
      start hunting and to capture the first prey. The lidocaine-treated animals
      captured the prey by using mostly the mouth, with little forepaw assistance, and
      were less effective in capturing the roaches. Moreover, while handling the prey,
      animals with ventrolateral striatal inactivation kept biting several parts of the
      prey, but failed to deliver the killing bite to the head, leaving them alive and
      moving, more likely to escape. Overall, the present findings suggest that the
      ventrolateral striatum implements the stereotyped actions seen during prey
      capture and handling, and may influence the motivational drive to start attacking
      the roaches, as well.

PMID- 17234220
TI  - Behavioral and physiological responses of guide dogs to a situation of emotional
      distress.
AB  - The aim of this study was to analyze the behavioral and physiological reactions
      of guide dogs in a distressing situation which promotes attachment behaviors
      towards their blind owners, and to compare such reactions with those of untrained
      or trainee dogs. The subjects were 57 adult Labrador and Golden retriever dogs
      (14 males, 43 females) belonging to four different groups: 19 Custody dogs, 13
      Apprentice dogs, 10 Guide dogs and 15 Pet dogs. Dogs were tested using the
      Strange Situation Test, consisting in seven 3-minute episodes in which the dogs
      were placed in an unfamiliar environment, introduced to an unfamiliar woman and
      subjected to separation from their human companion. Tests were video-recorded and
      behaviors were scored using a 5-second point sampling method. Polar Vantage
      telemetric system was used to record cardiac activity. ANOVAs for repeated
      measures with groups and breeds as independent variables, showed a more anxious
      reaction in pet dogs, which revealed a high degree of proximity seeking behavior.
      Cardiac activity increased during episodes characterized by the exclusive
      presence of the stranger, but this increase was more conspicuous in guide dogs
      than in custody and apprentice dogs. Golden retrievers showed more behaviors
      suggesting distress compared to Labrador retrievers. This study showed that guide
      dogs, when separated from their blind owner, reveal a controlled behavioral
      reaction that is however accompanied by a stronger cardiac activation.

PMID- 17234221
TI  - Exploration of the hypothalamic-pituitary-adrenal function as a tool to evaluate
      animal welfare.
AB  - Measuring HPA axis activity is the standard approach to the study of stress and
      welfare in farm animals. Although the reference technique is the use of blood
      plasma to measure glucocorticoid hormones (cortisol or corticosterone), several
      alternative methods such as the measurement of corticosteroids in saliva, urine
      or faeces have been developed to overcome the stress induced by blood sampling
      itself. In chronic stress situations, as is frequently the case in studies about
      farm animal welfare, hormonal secretions are usually unchanged but dynamic
      testing allows the demonstration of functional changes at several levels of the
      system, including the sensitization of the adrenal cortex to ACTH and the
      resistance of the axis to feedback inhibition by corticosteroids (dexamethasone
      suppression test). Beyond these procedural aspects, the main pitfall in the use
      of HPA axis activity is in the interpretation of experimental data. The large
      variability of the system has to be taken into consideration, since
      corticosteroid hormone secretion is usually pulsatile, follows diurnal and
      seasonal rhythms, is influenced by feed intake and environmental factors such as
      temperature and humidity, age and physiological state, just to cite the main
      sources of variation. The corresponding changes reflect the important role of
      glucocorticoid hormones in a number of basic physiological processes such as
      energy metabolism and central nervous system functioning. Furthermore, large
      differences have been found across species, breeds and individuals, which reflect
      the contribution of genetic factors and environmental influences, especially
      during development, in HPA axis functioning. Usually, these results will be
      integrated with data from behavioral observation, production and pathology
      records in a comprehensive approach of farm animal welfare.

PMID- 17234222
TI  - C-methylated and C-prenylated isoflavonoids from root extract of Desmodium
      uncinatum.
AB  - A pterocarpan, 1,9-dihydroxy-3-methoxy-2-methylpterocarpan (named uncinacarpan)
      and two isoflavanones, 5,7-dihydroxy-2',3',4'-trimethoxy-6-(3-methylbut-2
      enyl)isoflavanone (named uncinanone D) and 5,4'-dihydroxy-7,2'-dimethoxy-6
      methylisoflavanone (named uncinanone E), were isolated from the CH(2)Cl(2) root
      extract of Desmodium uncinatum (Jacq.) DC and characterised by spectroscopic
      methods. In addition, a rare pterocarpan edudiol and two known abietane
      diterpenes, 7-oxo-15-hydroxydehydroabietic acid and 7-hydroxycallitrisic acid
      were identified. The fraction of the root extract that was analysed induced
      germination of Striga hermonthica seeds, but none of the isolated compounds
      showed this activity.

PMID- 17234223
TI  - Semisynthesis and in vitro anticancer activities of andrographolide analogues.
AB  - The plant Andrographis paniculata found throughout Southeast Asia contains
      Andrographolide 1, a diterpenoid lactone, which has antitumour activities against
      in vitro and in vivo breast cancer models. In the present study, we report on the
      synthesis of andrographolide derivatives, 3,19-isopropylideneandrographolide (2),
      14-acetyl-3,19-isopropylideneandrographolide (3) and 14-acetylandrographolide
      (4), and their in vitro antitumour activities against a 2-cell line panel
      consisting of MCF-7 (breast cancer cell line) and HCT-116 (colon cancer cell
      line). Compounds 2 and 4 were also screened at the US National Cancer Institute
      (NCI) for their activities against a panel of 60 human cancer cell lines derived
      from nine cancer types. Compound 2 was found to be selective towards leukaemia
      and colon cancer cells, and compound 4 was selective towards leukaemia, ovarian
      and renal cancer cells at all the dose-response parameters. Compounds 2 and 4
      showed non-specific phase of the cell cycle arrest in MCF-7 cells treated at
      different intervals with different concentrations. NCI's COMPARE and SOM
      mechanistic analyses indicated that the anticancer activities of these new class
      of compounds were not similar to that of standard anticancer agents, suggesting
      novel mechanism(s) of action.

PMID- 17234224
TI  - Isozymes of plant hexokinase: occurrence, properties and functions.
AB  - Hexokinase (HK) occurs in all phyla, as an enzyme of the glycolytic pathway. Its
      importance in plant metabolism has emerged with compelling evidence that its
      preferential substrate, glucose, is both a nutrient and a signal molecule that
      controls development and expression of different classes of genes. A variety of
      plant tissues and organs have been shown to express multiple HK isoforms with
      different kinetic properties and subcellular localizations. Although plant HK is
      known to fulfill a catalytic function and act as a glucose sensor, the
      physiological relevance of plural isoforms and their contribution to either
      function are still poorly understood. We review here the current knowledge and
      hypotheses on the physiological roles of plant HK isoforms that have been
      identified and characterized. Recent findings provide hints on how the expression
      patterns, biochemical properties and subcellular localizations of HK isoforms may
      relate to their modes of action. Special attention is devoted to kinetic, mutant
      and transgenic data on HKs from Arabidopsis thaliana and the Solanaceae potato,
      tobacco, and tomato, as well as HK gene expression data from Arabidopsis public
      DNA microarray resources. Similarities and differences to known properties of
      animal and yeast HKs are also discussed as they may help to gain further insight
      into the functional adaptations of plant HKs.

PMID- 17234225
TI  - To be or not to be (a receptor).
AB  - In addition to cellular responses that are elicited by steroids involving the
      modulation of transcription in the nucleus, it is now generally accepted that
      additional phenomena occur that do not depend on the genome. However, there is a
      puzzling variety of candidate receptors described in the literature.

PMID- 17234226
TI  - Diesel exhaust particles induce endothelial dysfunction in apoE-/- mice.
AB  - BACKGROUND: Particulate air pollution can aggravate cardiovascular disease by
      mechanisms suggested to involve translocation of particles to the bloodstream and
      impairment of endothelial function, possibly dependent on present
      atherosclerosis. AIM: We investigated the effects of exposure to diesel exhaust
      particles (DEP) in vivo and ex vivo on vasomotor functions in aorta from apoE(-/
      ) mice with slight atherosclerosis and from normal apoE(+/+) mice. METHODS: DEP
      0, 0.5 or 5 mg/kg bodyweight in saline was administered i.p. The mice were
      sacrificed 1 h later and aorta ring segments were mounted on wire myographs.
      Segments from unexposed mice were also incubated ex vivo with 0, 10 and 100
      microg DEP/ml before measurement of vasomotor functions. RESULTS: Exposure to 0.5
      mg/kg DEP in vivo caused a decrease in the endothelium-dependent acetylcholine
      elicited vasorelaxation in apoE(-/-) mice, whereas the response was enhanced in
      apoE(+/+) mice. No significant change was observed after administration of 5
      mg/kg DEP. In vivo DEP exposure did not affect constriction induced by K(+) or
      phenylephrine. In vitro exposure to 100 microg DEP/ml enhanced acetylcholine
      induced relaxation and attenuated phenylephrine-induced constriction.
      Vasodilation induced by sodium nitroprusside was not affected by any DEP
      exposure. CONCLUSION: Exposure to DEP has acute effect on vascular functions.
      Endothelial dysfunction possibly due to decreased NO production as suggested by
      decreased acetylcholine-induced vasorelaxation and unchanged sodium nitroprusside
      response can be induced by DEP in vivo only in vessels of mice with some
      atherosclerosis.

PMID- 17234227
TI  - Iron supplement prevents lead-induced disruption of the blood-brain barrier
      during rat development.
AB  - Children are known to be venerable to lead (Pb) toxicity. The blood-brain barrier
      (BBB) in immature brain is particularly vulnerable to Pb insults. This study was
      designed to test the hypothesis that Pb exposure damaged the integrity of the BBB
      in young animals and iron (Fe) supplement may prevent against Pb-induced BBB
      disruption. Male weanling Sprague-Dawley rats were divided into four groups.
      Three groups of rats were exposed to Pb in drinking water containing 342 microg
      Pb/mL as Pb acetate, among which two groups were concurrently administered by
      oral gavage once every other day with 7 mg Fe/kg and 14 mg Fe/kg as FeSO(4)
      solution as the low and high Fe treatment group, respectively, for 6 weeks. The
      control group received sodium acetate in drinking water. Pb exposure
      significantly increased Pb concentrations in blood by 6.6-folds (p<0.05) and
      brain tissues by 1.5-2.0-folds (p<0.05) as compared to controls. Under the
      electron microscope, Pb exposure in young animals caused an extensive
      extravascular staining of lanthanum nitrate in brain parenchyma, suggesting a
      leakage of cerebral vasculature. Western blot showed that Pb treatment led to 29
      68% reduction (p<0.05) in the expression of occludin as compared to the controls.
      Fe supplement among Pb-exposed rats maintained the normal ultra-structure of the
      BBB and restored the expression of occludin to normal levels. Moreover, the low
      dose Fe supplement significantly reduced Pb levels in blood and brain tissues.
      These data suggest that Pb exposure disrupts the structure of the BBB in young
      animals. The increased BBB permeability may facilitate the accumulation of Pb. Fe
      supplement appears to protect the integrity of the BBB against Pb insults, a
      beneficial effect that may have significant clinical implications.

PMID- 17234228
TI  - Role of CYP2E1 and saturation kinetics in the bioactivation of thioacetamide:
      Effects of diet restriction and phenobarbital.
AB  - Thioacetamide (TA) undergoes saturation toxicokinetics in ad libitum (AL) fed
      rats. Diet restriction (DR) protects rats from lethal dose of TA despite
      increased bioactivation-mediated liver injury via CYP2E1 induction. While a low
      dose (50 mg TA/kg) produces 6-fold higher initial injury, a 12-fold higher dose
      produces delayed and mere 2.5-fold higher injury. The primary objective was to
      determine if this less-than-expected increase in injury is due to saturation
      toxicokinetics. Rats on AL and DR for 21 days received either 50 or 600 mg TA/kg
      i.p. T(1/2) and AUCs for TA and TA-S-oxide were consistent with saturable
      kinetics. Covalent binding of (14)C-TA-derived-radiolabel to liver macromolecules
      after low dose was 2-fold higher in DR than AL rats. However, following lethal
      dose, no differences were found between AL and DR. This lack of dose-dependent
      response appears to be due to saturation of bioactivation at the higher dose. The
      second objective was to investigate the effect of phenobarbital pretreatment (PB)
      on TA-initiated injury following a sub-lethal dose (500 mg/kg). PB induced
      CYP2B1/2 approximately 350-fold, but did not increase covalent binding of (14)C
      TA, TA-induced liver injury and mortality, suggesting that CYP2B1/2 has no major
      role in TA bioactivation. The third objective was to investigate the role of
      CYP2E1 using cyp2e1 knockout mice (KO). Injury was assessed over time (0-48 h) in
      wild type (WT) and KO mice after LD(100) dose (500 mg/kg) in WT. While WT mice
      exhibited robust injury which progressed to death, KO mice exhibited neither
      initiation nor progression of injury. These findings confirm that CYP2E1 is
      responsible for TA bioactivation.

PMID- 17234229
TI  - Tea and cancer prevention: molecular mechanisms and human relevance.
AB  - Tea made from the leaves of the plant Camellia sinensis is a popular beverage.
      The possible cancer-preventive activity of tea and tea polyphenols has been
      studied extensively. This article briefly reviews studies in animal models, cell
      lines, and possible relevance of these studies to the prevention of human cancer.
      The cancer-preventive activity of tea constituents have been demonstrated in many
      animal models including cancer of the skin, lung, oral cavity, esophagus,
      stomach, liver, pancreas, small intestine, colon, bladder, prostate, and mammary
      gland. The major active constituents are polyphenols, of which (-)
      epigallocatechin-3-gallate (EGCG) is most abundant, most active, and most
      studied, and caffeine. The molecular mechanisms of the cancer-preventive action,
      however, are just beginning to be understood. Studies in cell lines led to the
      proposal of many mechanisms on the action of EGCG. However, mechanisms based on
      studies with very high concentrations of EGCG may not be relevant to cancer
      prevention in vivo. The autooxidation of EGCG in cell culture may also produce
      activities that do not occur in many internal organs. In contrast to the cancer
      prevention activity demonstrated in different animal models, no such conclusion
      can be convincingly drawn from epidemiological studies on tea consumption and
      human cancers. Even though the human data are inconclusive, tea constituents may
      still be used for the prevention of cancer at selected organ sites if sufficient
      concentrations of the agent can be delivered to these organs. Some interesting
      examples in this area are discussed.

PMID- 17234230
TI  - Polyamines and nonmelanoma skin cancer.
AB  - Elevated levels of polyamines have long been associated with skin tumorigenesis.
      Tightly regulated metabolism of polyamines is critical for cell survival and
      normal skin homeostasis, and these controls are dysregulated in skin
      tumorigenesis. A key enzyme in polyamine biosynthesis, ornithine decarboxylase
      (ODC) is upregulated in skin tumors compared to normal skin. Use of transgenic
      mouse models has demonstrated that polyamines play an essential role in the early
      promotional phase of skin tumorigenesis. The formation of skin tumors in these
      transgenic mice is dependent upon polyamine biosynthesis, especially putrescine,
      since treatment with inhibitors of ODC activity blocks the formation of skin
      tumors and causes the rapid regression of existing tumors. Although the mechanism
      by which polyamines promote skin tumorigenesis are not well understood, elevated
      levels of polyamines have been shown to stimulate epidermal proliferation, alter
      keratinocyte differentiation status, increase neovascularization, and increase
      synthesis of extracellular matrix proteins in a manner similar to that seen in
      wound healing. It is becoming increasingly apparent that elevated polyamine
      levels activate not only epidermal cells but also underlying stromal cells in the
      skin to promote the development and progression of skin tumors. The inhibition of
      polyamine biosynthesis has potential to be an effective chemoprevention strategy
      for nonmelanoma skin cancer.

PMID- 17234231
TI  - The lathyrus toxin, beta-N-oxalyl-L-alpha,beta-diaminopropionic acid (ODAP), and
      homocysteic acid sensitize CA1 pyramidal neurons to cystine and L-2-amino-6
      phosphonohexanoic acid.
AB  - A brief exposure of hippocampal slices to L-quisqualic acid (QUIS) sensitizes CA1
      pyramidal neurons 30- to 250-fold to depolarization by certain excitatory amino
      acids analogues, e.g., L-2-amino-6-phosphonohexanoic acid (L-AP6), and by the
      endogenous compound, L-cystine. This phenomenon has been termed QUIS
      sensitization. A mechanism similar to that previously described for QUIS
      neurotoxicity has been proposed to describe QUIS sensitization. Specifically,
      QUIS has been shown to be sequestered into GABAergic interneurons by the System
      x(c)(-) and subsequently released by heteroexchange with cystine or L-AP6,
      resulting in activation of non-NMDA receptors. We now report two additional
      neurotoxins, the Lathyrus excitotoxin, beta-N-oxalyl-L-alpha,beta
      diaminopropionic acid (ODAP), and the endogenous compound, L-homocysteic acid
      (HCA), sensitize CA1 hippocampal neurons >50-fold to L-AP6 and >10-fold to
      cystine in a manner similar to QUIS. While the cystine- or L-AP6-mediated
      depolarization can be inhibited by the non-NMDA receptor antagonist CNQX in ODAP-
      or QUIS-sensitized slices, the NMDA antagonist D-AP5 inhibits depolarization by
      cystine or L-AP6 in HCA-sensitized slices. Thus, HCA is the first identified NMDA
      agonist that induces phosphonate or cystine sensitization. Like QUIS
      sensitization, the sensitization evoked by either ODAP or HCA can be reversed by
      a subsequent exposure to 2 mM alpha-aminoadipic acid. Finally, we have
      demonstrated that there is a correlation between the potency of inducers for
      triggering phosphonate or cystine sensitivity and their affinities for System
      x(c)(-) and either the non-NMDA or NMDA receptor. Thus, the results of this study
      support our previous model of QUIS sensitization and have important implications
      for the mechanisms of neurotoxicity, neurolathyrism and hyperhomocystinemia.

PMID- 17234232
TI  - Galactosyl ceramide expressed on dendritic cells can mediate HIV-1 transfer from
      monocyte derived dendritic cells to autologous T cells.
AB  - Mucosa, comprising epithelial and dendritic cells, are the major sites for Human
      Immunodeficiency Virus type 1 (HIV-1) transmission. There, DCs can capture
      incoming HIV-1 and in turn transfer virus to CD4(+) T lymphocytes in a two-phase
      process, thereby initiating HIV-1 dissemination. We show that the
      glycosphingolipid Galactosyl Ceramide (GalCer), acting as mucosal epithelial
      receptor for HIV-1, was expressed by human monocyte derived immature DCs (iDCs),
      human primary DCs isolated from blood and mucosal tissue and in situ on mucosal
      tissue and acts as HIV-1-gp41 receptor. Blocking both GalCer and CD4 with
      specific mAbs results in a >95% transfer inhibition of HIV-1 from human monocyte
      derived iDCs to autologous resting T cells. GalCer interaction with HIV-1
      controls the early infection-independent phase of HIV-1 transfer to T cells.
      Thus, GalCer appears as an initial receptor for HIV-1, common to both mucosal
      epithelial cells and iDCs.

PMID- 17234233
TI  - Preparation, stabilization and characterization of TiO(2) on thin polyethylene
      films (LDPE). Photocatalytic applications.
AB  - An innovative way to fix preformed nanocrystalline TiO(2) on low-density
      polyethylene film (LDPE-TiO(2)) is presented. The LDPE-TiO(2) film was able to
      mediate the complete photodiscoloration of Orange II using about seven times less
      catalyst than a TiO(2) suspension and proceeded with a photonic efficiency of
      approximately 0.02. The catalyst shows photostability over long operational
      periods during the photodiscoloration of the azo dye Orange II. The LDPE-TiO(2)
      catalyst leads to full dye discoloration under simulated solar light but only to
      a 30% TOC reduction since long-lived intermediates generated in solution seem to
      preclude full mineralization of the dye. Physical insight is provided into the
      mechanism of stabilization of the LDPE-TiO(2) composite during the photocatalytic
      process by X-ray photoelectron spectroscopy (XPS). The adherence of TiO(2) on
      LDPE is investigated by electron microscopy (EM) and atomic force microscopy
      (AFM). The thickness of the TiO(2) film is seen to vary between 1.25 and 1.69
      microm for an unused LDPE-TiO(2) film and between 1.31 and 1.50 microm for a
      sample irradiated 10h during Orange II discoloration pointing out to a higher
      compactness of the TiO(2) film after the photocatalysis.

PMID- 17234234
TI  - Cu(II) binding by dried biomass of red, green and brown macroalgae.
AB  - Dried biomass of the marine macroalgae Fucus spiralis and Fucus vesiculosus
      (brown), Ulva spp. (comprising Ulva linza, Ulva compressa and Ulva intestinalis)
      and Ulva lactuca (green), Palmaria palmata and Polysiphonia lanosa (red) were
      studied in terms of their Cu(II) biosorption performance. This is the first study
      of its kind to compare Cu(II) uptake by these seaweeds in the South-East of
      Ireland. Potentiometric and conductimetric titrations revealed a variety of
      functionalities on the seaweed surface including carboxyl and amino groups, which
      are capable of metal binding. It was also found that, of the seaweeds
      investigated, F. vesiculosus contained the greatest number of acidic surface
      binding sites while Palmaria palmata contained the least. The metal uptake
      capacities of the seaweeds increased with increasing pH and kinetic behaviour
      followed a similar pattern for all seaweeds: a rapid initial sorption period
      followed by a longer equilibrium period. P. palmata reached equilibrium within
      10min of exposure while F. vesiculosus required 60min. Correlation was found
      between the total number of acidic binding sites and the time taken to reach
      equilibrium. Fourier transform infra-red (FTIR) analysis of the seaweeds revealed
      the interaction of carboxyl, amino, sulphonate and hydroxyl groups on the seaweed
      surface with Cu(2+) ions while time course studies established the relative
      contribution of each of these groups in metal binding.

PMID- 17234235
TI  - Calcium fluoride recovery from fluoride wastewater in a fluidized bed reactor.
AB  - In order to contribute to better resource efficiency and industrial waste
      management leading to a sustainable production and consumption pattern new
      processes must be developed, which should be operated in such a way that waste
      production is reduced or avoided. Fluoride removal by precipitation generates
      huge amounts of a water rich sludge. Calcium fluoride is not recovered from the
      waste streams and it is not recycled due to the high water content and the low
      quality of the sludge. Crystallization process in a fluidized bed reactor (FBR)
      appears as an alternative technology to the conventional chemical precipitation
      process. In the crystallization process in a FBR silica sand is usually used as
      seed material, however silica is a deleterious impurity because it causes losses
      in the yield of HF and its content should be less than 1%. In this paper,
      granular calcite has been used as seed material in order to obtain synthetic
      calcium fluoride. According to the composition (CaF(2)>97%, SiO(2)<1%), the
      synthetic calcium fluoride from the crystallization process in a FBR is able to
      be recycled as raw material for the manufacture of hydrofluoric acid leading to a
      reduction of raw materials consumption. The crystallization process in a FBR to
      remove fluoride from industrial wastewaters contributes to an environmental
      friendly production, because it allows to reduce the waste production as well as
      to increase the recovery of materials.

PMID- 17234236
TI  - Phenotypic characterization of Escherichia coli through whole-cell fatty acid
      profiling to investigate host specificity.
AB  - The objective of the study was to investigate whole-cell fatty acid methyl ester
      (FAME) profiles of 605 Escherichia coli isolates to determine their host
      specificity. The isolates were cultured from six possible sources of fecal
      pollution; 180 isolates from sewage, 85 from dairy cow, 98 from chicken, 76 from
      swine, 94 from deer, and 72 from waterfowl, mostly geese and ducks. The FAME
      profiles were presented as the relative masses of 12 FAMEs identified in the
      isolates and it was found that none of the six hosts carried a "signature" FAME,
      a FAME that is uniquely associated with a particular host category. However, two
      sample t-test analyses indicated that the mean relative masses of seven FAMEs out
      of the 12 identified showed statistically significant differences (95% confidence
      interval) between isolates of human and non-human origins. In addition, a linear
      discriminant function based on mean relative mass variations in individual FAMEs
      classified the known-source isolates into their respective host categories with a
      47.6% average rate of correct classification (ARCC) in a six-way discriminant
      analysis. The ARCC increased to 61.3% when the individual hosts were pooled into
      larger categories of human, livestock, and wildlife. The accuracy was 75.5% when
      isolates of human origin were discriminated against those of non-human origins.
      Random cluster formation analysis indicated that the library size was sufficient
      to prevent random grouping among the isolates.

PMID- 17234237
TI  - Binding affinity of proanthocyanidin from waste Pinus radiata bark onto proline
      rich bovine achilles tendon collagen type I.
AB  - Binding affinity of proanthocyanidin (PA) purified from Pinus radiata bark waste
      onto bovine Achilles tendon collagen (type I) was studied. Adsorption of PA onto
      the collagen was optimized by examining pH, contact time and temperature. The
      adsorption was pH-dependent. The maximum adsorption capacity (Q(0)) of PA on
      collagen was found to be 211 mg g(-1) using the Langmuir isotherm. Comparison
      between two adsorbents also showed that collagen had higher adsorptivity of
      approximately 20% more than PVPP (polyvinyl polypyrrolidone). The high affinity
      between PA and collagen was further confirmed in solvent solubility experiments.
      The observed solvent resistance was thought to be mainly due to a hydrophobic
      stacking mechanism reinforced by hydrogen bonding. FT-IR spectra clearly
      indicated the presence of PA adsorbed on collagen. The results have interesting
      implications that PA can be a good protective agent for collagen against
      collagenase and other enzymes.

PMID- 17234238
TI  - A study on PCB, PCDD/PCDF industrial contamination in a mixed urban-agricultural
      area significantly affecting the food chain and the human exposure. Part I: soil
      and feed.
AB  - This study deals with a PCB, PCDD and PCDF contamination in Brescia, a city in
      the North-West of Italy, affecting an area with about 11000 inhabitants. The area
      is close to an industrial plant that produced, in total, some 31,000 ton of PCB.
      A relevant part of the polluted area is agricultural soil, where cattle were fed
      with polluted forage and farmers were consuming their own products, so that
      contamination led eventually to human exposure. Total levels of PCDD/Fs varied
      from 8 to 592 pgTE(WHO)/g for soil samples and when the dioxin-like PCBs (dl
      PCBs) are included, the levels varied from 14.6 to 1033.7 pgTE(WHO)/g. In several
      cases, the legal limit was exceeded by more than one order of magnitude, with the
      highest contamination in some agricultural areas and in the surrounding zones.
      For the forage samples, total levels of PCDD/Fs varied from 0.29 to 2.04
      pgTE(WHO)/g and, when dl-PCBs are included, this range increased from 2.04 to
      4.75 pgTE(WHO)/g. PCB contamination of the forage through vapor condensation
      seemed to be relevant. The toxic contribution of dl-PCBs is always relevant and
      must be considered for risk management. The main component of the contamination
      source is probably a heavy PCB mixture, such as Aroclor 1262. The study dealt
      generally with the contamination transfer of PCBs, PCDDs and PCDFs from soil up
      to humans across the food chain. Results on soils and forages are shown, while
      measurements concerning the contamination of the animals fed with contaminated
      forage, and the exposure of the farmers (through human serum analyses), as
      compared to general population, will be reported in a dedicated paper.

PMID- 17234239
TI  - Electrolytic trichloroethene degradation using mixed metal oxide coated titanium
      mesh electrodes.
AB  - Electrochemical systems provide a low cost, versatile, and controllable platform
      to potentially treat contaminants in water, including chlorinated solvents.
      Relative to bare metal or noble metal amended materials, dimensionally stable
      electrode materials such as mixed metal oxide coated titanium (Ti/MMO) have
      advantages in terms of stability and cost, important factors for sustainable
      remediation solutions. Here, we report the use of Ti/MMO as an effective cathode
      substrate for treatment of trichloroethene (TCE). TCE degradation in a batch
      reactor was measured as the decrease of TCE concentration over time and the
      corresponding evolution of chloride; notably, this occurred without the formation
      of commonly encountered chlorinated intermediates. The reaction was initiated
      when Ti/MMO cathode potentials were less than -0.8 V vs. the standard hydrogen
      electrode, and the rate of TCE degradation increased linearly with progressively
      more negative potentials. The maximum pseudo-first-order heterogeneous rate
      constant was approximately 0.05 cm min(-1), which is comparable to more commonly
      used cathode materials such as nickel. In laboratory-scale flow-though column
      reactors designed to simulate permeable reactive barriers (PRBs), TCE
      concentrations were reduced by 80-90%. The extent of TCE flux reduction increased
      with the applied potential difference across the electrodes and was largely
      insensitive to the spacing distance between the electrodes. This is the first
      report of the electrochemical reduction of a chlorinated organic contaminant at a
      Ti/MMO cathode, and these results support the use of this material in PRBs as a
      possible approach to manage TCE plume migration.

PMID- 17234240
TI  - Ryegrass uptake of soil Cu/Zn induced by EDTA/EDDS together with a vertical
      direct-current electrical field.
AB  - This paper summarizes a study on the application of vertical electric direct
      current (DC) to control the migration of metal complexes in soil columns when
      EDTA/[S,S]-ethylenediaminedisuccinic acid (EDDS) is used to enhance ryegrass
      uptake of Cu/Zn from contaminated soil. The results show that application of
      EDTA/EDDS significantly increased ryegrass uptake of Cu/Zn when compared with no
      EDTA/EDDS application and the Cu/Zn concentrations in all soil solutions sampled
      at three different levels of the soil column, i.e. 15, 30 and 50 cm. Application
      of vertical DC electrical field (1.0 V cm(-1)) through top anode (close to the
      surface) and bottom cathode caused redistribution of Cu/Zn concentrations.
      Copper/Zn concentrations significantly decreased in soil pore fluid that were
      sampled in the bottom sections of the column, suggesting an efficient control of
      the leaching risk of the Cu/Zn complexes when the vertical electrical field is
      applied. The shoot Cu concentration of ryegrass in the treatments with EDTA/EDDS
      and electrical field together was 0.46/0.61 times higher than that in treatments
      without electrical fields.

PMID- 17234241
TI  - Evaluation of pressure treated wood impact on landfill waste decomposition using
      a methane yield assay.
AB  - Research was conducted to investigate the potential impact of CCA-treated wood
      and other arsenic-free Cu-based preservative-treated wood on microorganisms,
      involved in the anaerobic decomposition of waste in landfills. Wood preservatives
      used included alkaline copper quat (ACQ), copper citrate (CC), copper boron azole
      (CBA), copper dimethyldithiocarbamate (CDDC), and chromated copper arsenate
      (CCA). The biochemical methane potential (BMP) assay was used to estimate the
      possible impacts. The methane yields of mixtures of preservative-treated wood or
      untreated wood with cellulose (group 1) and these wood samples only (group 2)
      were determined. An analysis of variance (ANOVA) test found that there were no
      significant differences among methane yields results in either group 1 or group
      2, at the 0.05 level of significance. The results indicate that under the
      conditions tested, none of the treated wood products evaluated were toxic to the
      methane-producing organisms. At the end of the assays, test bottle contents were
      analyzed for Cu, Cr, and As. When the fraction of each metal in the solution
      (relative to original metal in the wood, leachability %) was examined, As was
      present at the great extent. The leachability of As was in the range from 15.1%
      to 21.7% while relatively low leachability (1.7-7.6%) of Cu was observed.

PMID- 17234242
TI  - Persistent organic pollutants in atmospheric deposition and biomonitoring with
      Tillandsia usneoides (L.) in an industrialized area in Rio de Janeiro state,
      southeast Brazil--Part II: PCB and PAH.
AB  - Monitoring of immission of persistent organic pollutants in the industrialized
      area of Volta Redonda (V.R.) and in the National Park of Itatiaia (PNI) in
      southeast Brazil was performed using an endemic bromeliad species as biomonitor
      and measuring bulk deposition rates of polychlorinated biphenyls (PCB) and
      polycyclic aromatic hydrocarbons (PAH). For the sum of PCB, overall deposition
      rates were between 17 and 314 ng/(m2 day) in winter and between 43 and 81 ng/(m2
      day) in summer, respectively. Deposition rates of dioxin-like PCBs ranged from
      0.14 to 2.8 pg WHO-TEQ/(m2 day) in winter and from 0.90 to 4.3 pg WHO-TEQ/(m2
      day) in summer. PCB deposition rates (total PCB and WHO-TEQ) were in the same
      range in winter in V.R. and PNI. In summer, contamination levels in V.R. were 6
      10-folds higher than in PNI. PCB concentrations in biomonitor samples from V.R.
      and PNI were in the same range in summer and in winter. Concentrations of total
      PCB ranged from 14 to 95 microg/kg dry matter (d.m.) in winter and from 18 to 27
      microg/kg d.m. in summer, respectively. The TEQ values were between 1.7 and 4.1
      ng WHO-TEQ/kg d.m. in winter and between 1.9 and 2.9 ng WHO-TEQ/kg d.m. in
      summer. PCB concentrations of di-ortho PCB but not of non-ortho PCB were a factor
      of 2-4 lower in summer in both areas. PCB congener profiles resembled those from
      technical formulations. The profiles shifted to the higher chlorinated congeners
      in summer, probable due to revolatilisation of the lighter components at higher
      temperatures. PCB profiles in biomonitor resembled those from deposition samples
      and the shift to the heavier congeners in summer was even more pronounced. PAH
      deposition rates were in a similar range in both areas (131-2415 ng/(m2 day)).
      PAH levels in biomonitor samples from V.R. were about one order of magnitude
      higher than in samples from PNI indicating the impact of local sources. PAH
      profiles revealed stationary thermal processes as main source of contamination in
      V.R. whereas in PNI, biomass burning seems to be the main contamination source.

PMID- 17234243
TI  - Biological denitrification of high strength nitrate waste using preadapted
      denitrifying sludge.
AB  - Denitrification of synthetic high nitrate waste containing 9032 ppm NO(3)-N
      (40,000 ppm NO(3)) in a time period of only 6h has been achieved in our previous
      study using activated sludge. The activated sludge culture was acclimatized by a
      stepwise increase in the nitrate concentration of synthetic waste. In the present
      work, studies were carried out on the changing microbial population of the sludge
      and the physiology of nitrate metabolism during the various stages of adaptation
      process to high strength synthetic nitrate waste. During the course of
      adaptation, with an increase in the nitrate concentration, a sharp increase in
      the number of denitrifiers was found with an equally rapid decrease in the
      nitrifying community. Two key enzymes involved in the first two steps of the
      denitrification process were also studied during this period. The results of the
      study suggest that specific enzyme levels increase as the activated sludge adapts
      itself to higher nitrate concentrations. Biological denitrification of high
      nitrate waste is a slow process and to increase the rate of denitrification,
      parameters such as pH, temperature, C:N and biomass concentration of the process
      were optimized using orthogonal array method. Optimized conditions increased the
      specific nitrate reduction rate by 54% and specific nitrite reduction rate by
      45%.

PMID- 17234245
TI  - Competition and facilitation in industrial barrens: variation in performance of
      mountain birch seedlings with distance from nurse plants.
AB  - In stressful environments inter-plant facilitation is an important phenomenon co
      occurring with competition. However, most experiments in natural ecosystems have
      only contrasted "sheltered" and "exposed" microsites, thus missing possible non
      linearity of effects and not giving any information about the scale at which
      these interactions operate. In the current experiment we studied the net effect
      of nurse trees on mountain birch seedlings at various planting distances.
      Seedlings were planted in two highly stressful subarctic industrial barren sites
      around the nickel-copper smelter in Monchegorsk, NW Russia, at five distances
      (from 10 to 100 cm) from mature birch trees that were circa 100 cm in height. The
      survival and growth of seedlings were monitored for six years and the results
      were analyzed in respect to several environmental characteristics. Despite the
      fact that interaction strengths varied between years and between two study sites,
      both survival and growth of seedlings indicated optimum performance at middle
      distances and decreasing performance closer to and further from the nurse tree.
      We suggest that adverse effects on seedling performance at short distances are
      explained by competition and/or accumulation of pollutants under nurse plants,
      whereas at long distances these adverse effects appear due to lack of shelter, as
      shown by higher wind stress and lower soil water content.

PMID- 17234244
TI  - Thermodynamic analysis and kinetic modelling of dioxin formation and emissions
      from power boilers firing salt-laden hog fuel.
AB  - Both organic chlorine (e.g. PVC) and inorganic chlorides (e.g. NaCl) can be
      significant chlorine sources for dioxin and furan (PCDD/F) formation in
      combustion processes. This paper presents a thermodynamic analysis of high
      temperature salt chemistry. Its influence on PCDD/F formation in power boilers
      burning salt-laden wood waste is examined through the relationships between Cl2,
      HCl, NaCl(g) and NaCl(c). These analyses show that while HCl is a product of
      combustion of PVC-laden municipal solid waste, NaCl can be converted to HCl in
      hog fuel boilers by reactions with SO2 or alumino-silicate materials. Cl2 is a
      strong chlorinating agent for PCDD/F formation. HCl can be oxidized to Cl2 by O2,
      and Cl2 can be reduced back to HCl by SO2. The presence of sulphur at low
      concentrations thus enhances PCDD/F formation by increasing HCl concentrations.
      At high concentrations, sulphur inhibits de novo formation of PCDD/Fs through Cl2
      reduction by excess SO2. The effect of NH3, CO and NOx on PCDD/F formation is
      also discussed. A semi-empirical kinetic model is proposed. This model considers
      both precursor and de novo formation mechanisms. A simplified version is used as
      a stack emission model. The kinetic model indicates that stack dioxin emissions
      will increase linearly with decreasing electrostatic precipitator (ESP)
      efficiency and exponentially with increasing ESP temperature.

PMID- 17234246
TI  - Effect of arsenate on adsorption of Cd(II) by two variable charge soils.
AB  - The effect of arsenate on Cd(II) adsorption in two variable charge soils and the
      desorption of Cd(II) pre-adsorbed in the presence of arsenate were studied. The
      batch type experiments showed, the presence of arsenate led to increase in Cd(II)
      adsorption and the desorption of pre-adsorbed Cd(II). Further it was observed
      that the extent of adsorption and desorption of Cd(II) was greatly influenced by
      the initial concentrations of arsenate and Cd(II), the solution pH, and the
      nature of the soils. In general the increase in arsenate concentration and pH
      favored the uptake of Cd(II). Moreover, the arsenate concentration influenced
      more in Hyper-Rhodic Ferralsol than Rhodic Ferralsol at least for the Cd(II)
      adsorption/desorption. This may be due to the content of Fe/Al oxides in these
      soils. The larger the content of Fe/Al oxides, the more the adsorption of
      arsenate by the soil, hence greater the uptake of Cd(II). It can be assumed that
      the enhanced Cd(II) adsorption was mainly due to the increase in net negative
      surface charge of the soil induced by the adsorption of arsenate, because the
      presence of arsenate led to the decrease in zeta potential of these soil
      suspensions. The increase of electrostatically adsorbed Cd(II) was responsible
      for the increase in the desorption of Cd(II) pre-adsorbed in the presence of
      arsenate.

PMID- 17234247
TI  - Assessment of MSWI bottom ash organic carbon behavior: a biophysicochemical
      approach.
AB  - In order to understand the influence of organic components on the behavior of
      municipal solid waste incinerator bottom ash, samples from five French
      incinerators have been analyzed and compared. Biological and physico-chemical
      experiments were coupled with a view to developing a new rapid assessment method
      of bottom ash quality. Bottom ash had different total organic carbon contents
      ranging from 8.8 g kg(-1) to 37.4 g kg(-1). A part of this organic carbon can be
      leached into the environment or provide a substrate for microbial activity.
      Samples showed really different behaviors regarding these processes. Comparative
      results of leaching tests and biodegradation experiments showed a positive
      correlation between dissolved organic carbon and microbial activity. However,
      quantities of biodegraded or leached carbon are not representative of the
      samples' total organic carbon content. Thermal analyses in oxidizing conditions
      have revealed the presence of two fractions of organic components, showing
      different thermal behaviors. The associated mass losses were measured and
      compared to dissolved organic carbon. One of the two fractions can be directly
      linked to the leachable and easily biodegradable organic matter fraction.
      Calorimetric test is then presented as a novel analysis method that allows to
      provide rapid and global information concerning the characteristics of organic
      matter in bottom ash and its possible short and long-term evolution.

PMID- 17234248
TI  - A preliminary assessment of the potential environmental and human health impact
      of unsymmetrical dimethylhydrazine as a result of space activities.
AB  - A preliminary assessment of the potential environmental and human health impact
      of UDMH as a result of space activities has been carried out applying a
      theoretical approach in comparison with selected experimental data. The
      theoretical framework includes QSAR, ADME and PASS modelling as well as studies
      on the possible atmospheric dispersion of UDMH as calculated applying the OML
      Multi model. The possible impact on the environment and the human health has been
      elucidated and it has been concluded that UDMH especially inside the fall region
      of burned-out rocket stages constitute a significant threat to both environmental
      and human health, the latter as a results of the carcinogenic, mutagenic,
      convulsant, teratogenic and embryotoxic characteristics of UDMH in addition to
      the general toxic characteristics of the compound.

PMID- 17234249
TI  - Residential and biological exposure assessment of chemicals from a wood treatment
      plant.
AB  - This paper evaluates the results of contamination of residents and residential
      homes located in close proximity to a Wood Treatment Plant. The plant has
      produced treated wood products continuously since 1904. The principle chemicals
      used to treat the wood, which is primarily used for railroad ties (oblong objects
      laid perpendicular to the rails to act as a base for the tracks), are creosote
      and pentachlorophenol. For a number of years, the plant burned treated waste wood
      products containing creosote and pentachlorophenol. First the plant pressure
      impregnates the wood with creosote and pentachlorophenol, and then the wood is
      stacked on open ground to allow it to air dry. Chemicals from recently treated
      wood ties are allowed to evaporate into the air or drip onto the ground
      surrounding the stacked wood. Small drainage ditches carry the liquid wastes into
      larger water channels where eventually the waste streams are discharged into a
      river adjacent to the plant. The river serves as a source of drinking water for
      the nearby community. Prevailing wind patterns favor a drift of air emissions
      from the plant's boiler stack over the nearby community and its residents. Over
      the past few years, the town's residents have become increasingly concerned about
      their health status and have voiced concerns regarding multiple health problems
      (including cancer), possibly associated with plant discharges. The intention of
      this study is to examine a representative sample of the potentially affected
      residents and to evaluate their residential environment for the presence of
      dioxin and/or its congeners. Data obtained from EPA's Toxic Release Information
      (TRI) database revealed the plant routinely discharged creosote,
      pentachlorophenol, dioxin and dioxin-like compounds into the ambient air via
      fugitive air emissions and surface waste waters. Sampling of household dust and
      water sediment within and outside of residences within a 2-mile radius of the
      plant revealed the presence of significantly elevated levels of dioxins,
      principally octachlorodibenzo-p-dioxin (OCDD) and 1,2,3,4,6,7,8-hepta-CDD.
      Biomonitoring of 29 subjects identified the presence of significantly elevated
      chlorinated dioxins and furan levels (OCDD=1049 ppt for exposed and 374 ppt for
      controls and 1,2,3,4,6,7,8-hepta CDD=132 ppt for exposed and 45.1 ppt for
      controls). These levels are consistent with exposures to pentachlorophenol in
      this group of subjects. And they confirm the presence of unsafe levels of
      chlorinated dioxins in these persons.

PMID- 17234250
TI  - Mandarin peelings: the best carbon source to produce laccase by static cultures
      of Trametes pubescens.
AB  - In the present study, we investigated the effect of different carbon sources
      (glucose, glycerol and ground mandarin peelings) on laccase production by
      Trametes pubescens grown on stainless steel sponges under static conditions. The
      cultures with ground mandarin peelings gave the highest laccase activities,
      showing values of about 100 U l(-1). This is a very interesting result, since
      mandarin peelings are common agricultural wastes in some regions such as
      Mediterranean and Asiatic countries. Therefore, their reutilisation, besides
      reducing medium cost, also helps to solve the pollution problems caused by their
      disposal. Also, we studied the effect of supplementing the culture medium with
      different potential laccase-inducing compounds (ABTS, Tween 20, soya oil,
      Malaquite Green, Cu(2+), tannic acid) on laccase production. Soya oil was the
      best inducer of laccase activities, attaining values 4-fold higher than those
      obtained in the reference cultures.

PMID- 17234251
TI  - Persistent organic pollutants in 9/11 world trade center rescue workers:
      reduction following detoxification.
AB  - Exposure to toxins following the September 11, 2001 attack on and collapse of the
      World Trade Center (WTC) is of particular concern given the ultra fine
      particulate dust cloud, high temperature combustion, and months-long fire.
      Firefighters, paramedics, police and sanitation crews are among the approximately
      40000 personnel who labored for weeks and months on rescue and cleanup efforts.
      Many of the rescue workers have subsequently developed symptoms that remain
      unresolved with time. This study characterizes body burdens of polychlorinated
      biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and polychlorinated
      dioxins (PCDDs) in rescue workers and citizens exposed following the WTC
      collapse. Our research includes a pilot evaluation of a detoxification method
      aimed at reducing toxic burden. Many congeners were found at elevated levels, in
      ranges associated with occupational exposures. Post-detoxification testing
      revealed reductions in these congeners and despite the small study size, some
      reductions were statistically significant. Health symptoms completely resolved or
      were satisfactorily improved on completion of treatment. These results argue for
      a larger treatment study of this method and an overall treatment approach to
      address toxic burden.

PMID- 17234252
TI  - Persistent organic pollutants in atmospheric deposition and biomonitoring with
      Tillandsia Usneoides (L.) in an industrialized area in Rio de Janeiro state,
      south east Brazil--Part I: PCDD and PCDF.
AB  - Monitoring of immission of persistent organic pollutants in the industrialized
      area of Volta Redonda (V.R.) and in the National Park of Itatiaia (PNI) in
      southeast Brazil was performed using an endemic Bromeliad species as biomonitor
      and measuring total deposition rates on funnels covered with polyurethane foams.
      Samples were collected during 78 days in V.R. and 95 days in PNI in winter (dry
      season, June-August 2003) and during 114 days in both areas in summer (rainy
      season, December 2003-February 2004). The PCDD/PCDF deposition rates ranged from
      0.10 to 1.9 pg WHO-TEQ/(m2 day) in winter and from 0.11 to 2.2 pg WHO-TEQ/(m2
      day) in summer. Deposition rates found in V.R. in summer were four- to ninefold
      higher than those measured in PNI, while in winter deposition rates in both
      regions were in the same range. Deposition rates in V.R. in summer were about
      five fold lower than those measured in 1996. PCDD/PCDF levels in biomonitor
      samples were between 0.95 and 14.6 ng WHO-TEQ/kg d.m. in winter and between 2.2
      and 5.2 ng WHO-TEQ/kg d.m. in summer. In winter, concentrations found in V.R.
      were up to 11 times higher than those found in PNI, while in summer the levels
      measured in both areas were comparable. The homologue and isomer profiles found
      in the deposition as well as in the biomonitor samples from V.R. indicate that
      steel production is the main source of contamination in the region, whereas in
      PNI, the long range transport of these pollutants is the predominant
      contamination pathway.

PMID- 17234253
TI  - A high loading overland flow system: Impacts on soil characteristics, grass
      constituents, yields and nutrient removal.
AB  - The objectives of this paper are to determine effects of different grass species
      and their harvests on pollutant removal, elucidate impacts on soil
      characteristics and grass constituents, observe grass yield and quantify nutrient
      uptake by vegetation in an overland flow system (OLFS). Polluted creek water was
      applied to eight channels in the OLFS, which were planted with Paragrass,
      Nilegrass, Cattail, and Vetiver, with each two channels being randomly planted
      with a given grass species. The grass in one channel was harvested while that in
      the other channel was not. At a high rate of 27.8 m d(-1) hydraulic loading, the
      removal efficiencies of conventional pollutants such as BOD, COD, suspended
      solids (SS), and total coliforms in wastewater are not affected by the type of
      the grasses species, but those of nitrogen and phosphorus are affected by
      different species. Overall average removal efficiencies of BOD, COD, SS, ammonia,
      total nitrogen, total phosphorus and total coliforms through the OLFS are 42%,
      48%, 78%, 47%, 40%, 33% and 89%, respectively. The concentration of nitrate,
      however, increases due to nitrification. Soil characteristics in OLFS have been
      changed significantly; specific conductivity, organic matter, exchangeable
      magnesium, extractable copper and zinc in soils all increase with time while pHs
      decrease. During the winter season, there is a significant accumulation of
      nitrate in grass with the subsequent reduction during the active growing season
      (Spring). The contents of nitrate and phosphorus in grass tissue are higher than
      those of grass in general pastureland, probably due to nutrient luxury uptake by
      grass. The overall grass yield, growth rate and nutrient uptake are quantified
      and implication of such high rate OLFS discussed.

PMID- 17234254
TI  - Androgenic and antiandrogenic activities in water and sediment samples from the
      river Lambro, Italy, detected by yeast androgen screen and chemical analyses.
AB  - The river Lambro is the most polluted tributary of the river Po in North Italy
      and was chosen as a representative water course discharging industrialized areas.
      Water and sediment samples of the river Lambro were investigated regarding the
      presence of endocrine disrupting compounds. A combined procedure was used
      consisting of solid-phase extraction and HPLC based fractionation of samples, of
      screening for (anti)androgenic activity using the yeast androgen screen (YAS) and
      of chemical analysis using HPLC-MS/MS and GC-MS. Androgenic and antiandrogenic
      activities were found in specific fractions of the water and sediment while the
      total extracts showed antiandrogenic activity only. The chemical analysis of the
      fractions and total extracts with antiandrogenic activities revealed the presence
      of compounds with suspected antiandrogenic potency such as bisphenol A,
      iprodione, nonylphenol, p,p'-DDE and tert-octylphenol but other unknown compounds
      contributed mainly to the observed antiandrogenic activities. The antiandrogenic
      load of the river Lambro ranged between 1.34 and 17.1 microM flutamide
      equivalents and may pose a risk to aquatic environments. Future screenings for
      EDC in the environment that have the potential to interfere with reproduction of
      aquatic organisms should be extended to different modes of actions including
      (anti)androgenic ones.

PMID- 17234255
TI  - Trace element partitioning and soil particle characterisation around mining and
      smelting areas at Tharsis, Riotinto and Huelva, SW Spain.
AB  - Trace elements may present an environmental hazard in the vicinity of mining and
      smelting activities. However, the factors controlling trace element distribution
      in soils around ancient and modern mining and smelting areas are not always
      clear. Tharsis, Riotinto and Huelva are located in the Iberian Pyrite Belt in SW
      Spain. Tharsis and Riotinto mines have been exploited since 2500 B.C., with
      intensive smelting taking place. Huelva, established in 1970 and using the Flash
      Furnace Outokumpu process, is currently one of the largest smelter in the world.
      Pyrite and chalcopyrite ore have been intensively smelted for Cu. However,
      unusually for smelters and mines of a similar size, the elevated trace element
      concentrations in soils were found to be restricted to the immediate vicinity of
      the mines and smelters, being found up to a maximum of 2 km from the mines and
      smelters at Tharsis, Riotinto and Huelva. Trace element partitioning (over 2/3 of
      trace elements found in the residual immobile fraction of soils at Tharsis) and
      soil particles examination by SEM-EDX showed that trace elements were not
      adsorbed onto soil particles, but were included within the matrix of large trace
      element-rich Fe silicate slag particles (i.e. 1 mm O at least 1 wt.% As, Cu and
      Zn, and 2 wt.% Pb). Slag particle large size (1 mm O) was found to control the
      geographically restricted trace element distribution in soils at Tharsis,
      Riotinto and Huelva, since large heavy particles could not have been transported
      long distances. Distribution and partitioning indicated that impacts to the
      environment as a result of mining and smelting should remain minimal in the
      region.

PMID- 17234256
TI  - Primary production in headwater streams of the Seine basin: the Grand Morin river
      case study.
AB  - Periphytic biomass has an important influence on the water quality of many
      shallow streams. The purpose of this paper is to synthesize the knowledge
      obtained on periphyton during the PIREN Seine research program. Periphyton was
      sampled using chl a measurements by acetone extraction and oxygen measurements
      with microelectrodes. The experiments reveal the presence of an important fixed
      biomass ranging between 123 and 850 mgchl a m(-2) and the mean gross production
      (photosynthesis) is shown to range between 180 and 315 mgC m(-2) h(-1). An
      independent approach was performed using the ProSe model, which simulates
      transport and biogeochemical processes in 22 km of the Grand Morin stream. A
      strong agreement between in situ measurements and the model results was obtained.
      The gross production obtained using ProSe is 220 mgC m(-2) h(-1) for the
      periphyton, which matches the experimental data. Although the net photosynthetic
      activity of the phytoplankton (0.84 gC gC(-1) d(-1)) is higher than the
      periphytic one (0.33 gC gC(-1) d(-1)), the absolute periphytic activity is
      greater since the mean biomass (3.4 gC m(-)(2)) is 10 times higher than the
      phytoplanktonic one (0.3 gC m(-2)), due to the short residence time of the water
      body (1.5d).

PMID- 17234257
TI  - Using doubly-labeled water measurements of human energy expenditure to estimate
      inhalation rates.
AB  - Doubly-labeled water (DLW) data is recognized as an improvement over alternative
      methods to quantify human energy expenditure. Previously, energy expenditure has
      been estimated indirectly using heart-rate monitoring, calorimetry, or
      accelerometer measurements. Inhalation rate estimates can benefit from improved
      energy expenditure estimates using equations developed by Layton. DLW methods are
      advantageous for several reasons: the database is robust, they are direct
      measures, subjects are free-living, and the observation period is longer than
      what is possible from staged activity measures. DLW energy data is an improvement
      over previous inhalation estimates based on dietary recall survey data. Mean long
      term inhalation rates of 16 m3/day and 13 m3/day, for physically active adult men
      and women, respectively, were derived based on DLW estimates of energy expended.
      The range of human energy expenditure is narrow with the maximum energy
      expenditure not likely greater than twice the minimum.

PMID- 17234258
TI  - Factors contributing to the internal loading of phosphorus from anoxic sediments
      in six Maine, USA, lakes.
AB  - Phosphorus (P) is the limiting macronutrient for primary production in most
      lakes. Seasonal anoxia in the hypolimnion of lakes has been strongly correlated
      with internal P loading to the water column. Gravimetric sediment cores were
      collected before and after the onset of anoxia in six Maine (USA) lakes during
      the summer of 2003. This study investigates the relative importance of P
      sequestration by aluminum hydroxide (Al(OH)3(s)), and ferric (oxy)hydroxide
      (Fe(OH)3(S)) dissolution with subsequent P release in lakes with varying trophic
      status. Two lakes, Pennesseewassee and Highland, are oligotrophic. The remaining
      lakes, China, Cobbosseecontee, Webber and Salmon, have varying levels of
      productivity. Sediment P, Al and Fe in the top 10 cm were extracted sequentially
      using ammonium chloride (NH4Cl), bicarbonate-dithionite (BD), and sodium
      hydroxide (NaOH) at 25 degrees C. The results suggest that a sediment [NH4Cl
      Al+BD-Al+NaOH25-Al]:[NH4Cl-Fe+BD-Fe] molar ratio >3 and a sediment [NaOH25
      Al]:[NH4Cl-P+BD-P] molar ratio >25 predict low P flux from sediments during the
      development of anoxia, as proposed by Kopacek et al. [Kopacek J, Borovec J,
      Hejzlar J, Ulrich K, Norton S, Amirbahman A. Aluminum control of Phosphorus
      Sorption in Lake Sediments. Environ Sci Technol 2005; 39: 8784-8789.], despite
      the development of anoxia in and the release of Fe(II) from the hypolimnia of the
      two study lakes. However, when these molar ratios are not exceeded the model does
      not adequately describe sedimentary P flux. The application of the model proposed
      by Kopacek et al. to Cobbosseecontee Lake suggests that its sediment may be a
      source of P to the water column. However, water column data indicate little to no
      sedimentary P flux. Therefore, the lack of P flux may be attributed to the
      absence of Fe(III) reduction in the Cobbosseecontee Lake sediment or perhaps to
      the slow diagenesis of organically-bound P.

PMID- 17234259
TI  - Weakened spindle checkpoint with reduced BubR1 expression in paclitaxel-resistant
      ovarian carcinoma cell line SKOV3-TR30.
AB  - OBJECTIVE: Paclitaxel sensitivity has recently been associated with the spindle
      checkpoint. The aim of our study is to investigate the status of spindle
      checkpoint and the alteration of its major components in phenotype with acquired
      paclitaxel resistance in ovarian carcinoma. METHODS: A paclitaxel-resistant
      ovarian carcinoma cell line, SKOV3-TR30, with the resistant ability of 27-fold
      greater than its parental cell line, was derived from SKOV3 cell line. The
      competence of spindle checkpoint and the expression of the major spindle
      checkpoint proteins (BubR1 and Mad2) in SKOV3-TR30 cells were investigated.
      RESULTS: Mitotic index and flow cytometric analysis revealed that SKOV3-TR30
      cells were not arrested in M phase in contrast to SKOV3, which showed a clear
      mitotic arrest in the presence of paclitaxel or nocodazole. The expressions of
      securin and cyclin B in SKOV3-TR30 cells were significantly lower than those in
      SKOV3 cells, indicating the premature degradation of APC substrates in SKOV3-TR30
      cells in response to spindle damagers. Chromosome spread analysis showed
      increased rate of premature sister chromatid segregation in SKOV3-TR30 cells. The
      expression of spindle checkpoint protein BubR1 was evidently lower in SKOV3-TR30
      cells than that in SKOV3 cells. However, there was no significant difference in
      Mad2 expression between SKOV3-TR30 and SKOV3 cells. CONCLUSIONS: This study
      demonstrates that weakened spindle checkpoint with reduced expression of BubR1,
      but not Mad2, is associated with acquired paclitaxel resistance in ovarian
      carcinoma cells.

PMID- 17234260
TI  - Effect of intravenously administered iron sucrose on the prevention of anemia in
      the cervical cancer patients treated with concurrent chemoradiotherapy.
AB  - OBJECTIVE: The incidence of anemia in the cervical cancer patients treated with
      concurrent chemoradiotherapy is estimated to be more than 50%. Transfusion has
      been the mainstay of hematologic support with its inherent hazards including
      infection and transfusion reaction. The aim of this study was to examine the
      impact of intravenously administered iron sucrose on the prevention of anemia in
      the cervical cancer patients undergoing concurrent chemoradiotherapy. METHODS:
      From Oct. 2003 to Dec. 2005, 75 patients were treated with platinum-based
      concurrent chemoradiotherapy. Thirty patients received 200 mg of iron sucrose
      intravenously (study group) and 45 patients did not receive it (control group).
      RESULTS: In the study group, only 12 (40.0%) patients required blood
      transfusions, whereas 29 (64.0%) patients in the control group needed blood
      transfusions (P=0.04). Mean transfusion units were 1.87 units in the study group
      and 3.58 units in the control group (P=0.04). CONCLUSION: This study showed that
      intravenous supply of iron sucrose could decrease transfusion requirement and
      increase serum hemoglobin level in patients with cervical carcinoma undergoing
      concurrent chemoradiotherapy. Therefore, intravenously administered iron sucrose
      would be effective in the prevention of anemia of cervical cancer patients
      receiving concurrent chemoradiotherapy.

PMID- 17234261
TI  - Genistein-induced apoptosis and autophagocytosis in ovarian cancer cells.
AB  - OBJECTIVE: Genistein, a naturally occurring isoflavenoid abundant in soy
      products, has anti-neoplastic activity in multiple tumor types. There are several
      mechanisms reported for genistein's anti-neoplastic activity. In the present
      study, we studied the mechanism of genistein-induced cell death in ovarian cancer
      cells. METHODS: The effect of genistein on the induction of apoptosis, autophagy,
      and inhibition of glucose uptake in ovarian cancer cells was determined. The
      effect of genistein on the expression of phosphorylated Akt was determined by
      immunoblotting. RESULTS: Genistein is cytotoxic to ovarian cancer cells. The
      mechanism of genistein-induced cell death includes both apoptosis and autophagy.
      Because autophagy is typically an adaptive response to nutrient starvation, we
      hypothesized that genistein could induce a starvation-like signaling response. We
      show here that genistein treatment results in caspase-independent cell death with
      hallmarks of autophagy. Genistein treatment dramatically inhibits glucose uptake
      in ovarian cancer cells, and methyl pyruvate, a cell-permeable 3-carbon substrate
      for oxidative phosphorylation and fatty acid synthesis, rescues cells from
      genistein-induced autophagy. In addition, genistein treatment results in reduced
      levels of phosphorylated Akt, which may contribute towards a mechanism to limit
      glucose utilization. CONCLUSIONS: Most conventional chemotherapeutic agents
      induce apoptotic cell death. Because genistein can induce both apoptotic and
      autophagic cell death, it has the potential to circumvent chemoresistance due to
      alterations in apoptotic signaling.

PMID- 17234262
TI  - The antinociceptive effect of morphine is reversed by okadaic acid in morphine
      naive but not in morphine-tolerant mice.
AB  - The activation of specific subtypes of serine/threonine protein phosphatases
      (PPs) plays a role in the antinociceptive effect of acute morphine, but it is not
      known whether these enzymes are involved in morphine-induced antinociception in
      morphine-tolerant animals. We evaluated the effects of both okadaic acid (a
      selective inhibitor of some serine/threonine PPs) and its inactive analogue L
      norokadaone on the antinociception induced by morphine in morphine-naive and 
      tolerant female mice in the tail-flick test. Okadaic acid (0.01 and 1 pg/mouse,
      i.c.v.), but not L-norokadaone (1 pg/mouse, i.c.v.), antagonized in a dose
      dependent way the antinociception induced by morphine (1-16 mg/kg, s.c.) in
      morphine-naive animals. However, both okadaic acid (0.01 and 1 pg/mouse, i.c.v.)
      and L-norokadaone (1 pg/mouse, i.c.v.) were unable to modify the antinociceptive
      effect of morphine in morphine-tolerant mice. These results suggest that in
      morphine-induced thermal analgesia, the role of serine/threonine PPs highly
      sensitive to okadaic acid is different in morphine-tolerant and morphine-naive
      female mice.

PMID- 17234264
TI  - Stability and change in personality type membership and anxiety in adolescence.
AB  - Although the stability and changeability of personality has long been debated,
      many studies now agree that personality changes over the life course. Although
      the changes in rank-order and mean-level stability are well established, the
      stability in personality type membership during adolescence is not yet clear.
      Little research has been conducted on the associations between change in
      personality type membership and anxiety. A total of 827 adolescents (10-20 years)
      completed personality and anxiety questionnaires on 2 waves of the CONflict And
      Management Of RElationships study (CONAMORE). We found that the stability in
      personality type membership was moderate. The change from undercontroller to
      overcontroller was the most frequently occurring change. Furthermore, the
      stability in type membership was related to stability in anxiety level and change
      in type membership was related to anxiety change. More specifically, the
      resilient-overcontroller group demonstrated an increase in anxiety level, whereas
      the overcontroller-resilient group demonstrated a decrease.

PMID- 17234263
TI  - Misperceptions regarding influenza vaccine safety for individuals with chronic
      medical illness.
AB  - BACKGROUND: Influenza immunization is recommended for adults >or=50 years,
      healthy children 6-59 months and individuals with a chronic medical condition.
      OBJECTIVES: To compare respondents' perceptions of safety of immunization for
      children and adults both with and without chronic medical conditions. METHODS: We
      surveyed parents of 828 randomly selected healthy children aged 6-21 months of
      age from 5 pediatric practices in Denver, Colorado between August and October of
      2003. RESULTS: The survey response rate was 57% (n=472). Although 65% of parents
      thought influenza immunization was safe for healthy 1 year olds, only 40%
      considered it safe for 1 year olds with a chronic condition. Similarly, 86%
      judged it safe in healthy 70 year olds versus 50% in 70 year olds with a chronic
      condition. CONCLUSIONS: Educational efforts to encourage influenza immunization
      in individuals with chronic illnesses should highlight the message that a chronic
      medical condition is an indication for immunization and does not confer
      additional risk of complications from vaccination. Further research is needed to
      confirm and better understand the observed perception of vulnerability to adverse
      events of vaccines in those with chronic illness.

PMID- 17234265
TI  - No cell is an island unto itself: the stromal microenvironment in chronic
      lymphocytic leukemia.

PMID- 17234266
TI  - The type II interleukin-1 receptor (IL-1RII) of the bony fish gilthead seabream
      Sparus aurata is strongly induced after infection and tightly regulated at
      transcriptional and post-transcriptional levels.
AB  - Interleukin-1beta (IL-1beta) is the prototypic pro-inflammatory cytokine. All the
      biological effects of IL-1beta are mediated through interaction with type 1 IL-1
      receptor (IL-1RI), whereas another receptor, called type 2 IL-1R (IL-1RII), lacks
      an intracellular signalling domain and acts as a decoy receptor that down
      regulates responses to IL-1beta. Although both receptors are present in bony
      fish, their expression and biological role in the regulation of IL-1beta activity
      in non-mammalian vertebrates remain to be established. In this study, a homologue
      of mammalian IL-1RII was isolated and characterized in the gilthead seabream
      (Sparus aurata). The seabream IL-1RII harboured two Ig-like domains in its
      extracellular region and a short cytoplasmic tail lacking a signalling domain.
      The seabream IL-1RII cDNA showed an unexpectedly long 3'UTR compared with that
      from other species and contained three ATTTA instability motifs, which seem to be
      responsible for its relatively short half-life (less than 2h). The expression of
      seabream IL-1RII was dramatically up-regulated after infection with Vibrio
      anguillarum in all the immune tissues examined and was even more strongly induced
      than the IL-1beta gene in the head kidney, spleen and liver. Strikingly, the mRNA
      levels of IL-1RII were 15-fold higher than those of IL-1beta in the liver,
      suggesting a role for this organ in the neutralization of IL-1beta leaking into
      the systemic circulation from the sites of inflammation. In vitro, bacterial DNA
      and flagellin increased the mRNA levels of IL-1RII in macrophages, while only
      flagellin was able to weakly induce its expression in acidophilic granulocytes.
      Finally, the seabream IL-1RII was localized in the plasma membrane when expressed
      in HEK293 cells and was able to bind IL-1beta.

PMID- 17234267
TI  - Gene conversion mutation in crystallin, beta-B2 (CRYBB2) in a Chilean family with
      autosomal dominant cataract.
AB  - PURPOSE: To map and identify the mutated gene for autosomal dominant cataract
      (ADC) in a large Chilean family (ADC53). DESIGN: Experimental study.
      PARTICIPANTS: Large Chilean family with ADCs. METHODS: Linkage analyses using
      genome-wide polymorphic DNA markers were performed on a family with variable
      expression of cataracts to map the mutated gene to a chromosome; 2-point lod
      scores were calculated. Candidate genes in the region of the maximum lod score
      were sequenced. We compared haplotypes (alleles at closely linked markers) in
      families with previously reported mutations of the crystallin, beta-B2 gene
      (CRYBB2). MAIN OUTCOME MEASURES: Identification of the causative mutation in the
      ADC53 family. RESULTS: The ADC locus mapped to chromosome 22 in the region of a
      cluster of lens beta crystallin genes (CRYBB3, CRYBB2, CRYBB1, and CRYBA4 and the
      pseudogene CRYBB2P1). We sequenced CRYBB1 and CRYBB2 and found a previously
      reported mutation and a variant in exon 6 of CRYBB2 that cosegregate with the
      disease; these changes in CRYBB2 are in the reference (normal) sequence of an
      adjacent gene CRYBB2P1, a pseudogene. The haplotypes in the ADC53 Chilean family
      were different from the 2 previously reported families with the mutation.
      CONCLUSIONS: The cataracts in the ADC53 Chilean family are caused by a mutation
      in the CRYBB2 gene; as the 2 variations in CRYBB2 are identical to the reference
      sequence of pseudogene CRYBB2P1, which has over 97% homology to CRYBB2, a gene
      conversion probably has occurred. Based on haplotype analyses, the mutation and
      variant are likely to be caused by independent gene conversions in our family and
      the previously reported families.

PMID- 17234268
TI  - Copper(II) interaction with 3,5-diisopropylsalicylic acid (Dips): new insights on
      its role as a potential *OH inactivating ligand.
AB  - The purpose of this study was to identify the low molecular mass complexes formed
      between copper(II) and 3,5-diisopropylsalicylic acid (Dips) in physiological
      conditions. Copper(II)-Dips complex equilibria were determined using glass
      electrode potentiometry and their solution structures checked by UV-visible (UV
      vis) spectrophotometry. Because of the low solubility of Dips in water, the
      equilibria were investigated in different water/ethanol mixtures. Formation
      constants were extrapolated to 100% water and then compared with the values
      obtained for the other anti-inflammatory drugs previously studied. Given the
      prime role of histidine as the copper(II) ligand in blood plasma, copper(II)
      histidine-Dips ternary equilibria were studied under similar experimental
      conditions. Computer simulations of copper(II) distribution relative to different
      biofluids, gastrointestinal (g.i.) fluid and blood plasma, show that like
      salicylic and anthranilic acids, Dips favors g.i. copper absorption, but cannot
      exert any significant influence on plasma copper distribution. Moreover, Dips can
      mobilize increasing fractions of copper(II) as the pH decreases. In conclusion,
      Dips seems to correspond to the notion of *OH-inactivating ligand (OIL) as
      determined for anthranilic acid.

PMID- 17234269
TI  - The role of metal ion binding in generating 8-hydroxy-2'-deoxyguanosine from the
      nucleoside 2'-deoxyguanosine and the nucleotide 2'-deoxyguanosine-5'
      monophosphate.
AB  - The metal ions Cu(II), Fe(II), and Cr(III) were allowed to react with H(2)O(2) in
      the presence of either the mononucleoside 2'-deoxyguanosine (dG) or the
      mononucleotide 2'-deoxyguanosine-5'-monophosphate (dGMP). The percentage of
      reacted dG or dGMP that formed the oxidative damage marker 8-hydroxy-2'
      deoxyguanosine (8-OH-dG) was monitored. Oxidative damage from reactions involving
      Cu(II) appear dependent on an interaction between copper and N7 on the guanine
      base. Any interactions involving the phosphate group have little additional
      effect on overall oxidative damage or 8-OH-dG production. Reactions involving
      Fe(II) seem very dependent on an interaction that may involve both N7 on the
      guanine base and the phosphate group. This interaction may slow oxidation of
      Fe(II) to Fe(III) in solution, keeping iron in a readily available form to
      undergo the Fenton reaction. Chromium(III) appears to interact with the phosphate
      group of dGMP, resulting in significant overall oxidative damage. However,
      production of 8-OH-dG appears to be very dependent on the ability of Cr(III) to
      interact with N7 on the guanine base, an interaction that seems to be weak for
      both the mononucleoside and mononucleotide.

PMID- 17234270
TI  - Manganese(II) tri-tert-butoxysilanethiolate complexes with imidazole-based
      coligands: a neutral complex with four independent ligands and MNOS2 core (M=Mn)
      related to the liver alcohol dehydrogenase catalytic center (M=Zn).
AB  - The reaction of [Mn{SSi(OBu(t))3}2(MeOH)4] with imidazole and its two methyl
      substituted derivatives leads to different types of heteroleptic manganese(II)
      thiolate complexes. Reaction with 1-methylimidazole gives the silanethiolate
      devoid of methanol but with two nitrogen ligands and thus central MnN(2)S(2)
      core. The reaction with imidazole leads to the methanol solvated complex with
      only one nitrogen ligand but manganese coordination sphere enlarged to
      MnO(2)NS(2) due to an O,S-chelation by tri-tert-butoxysilanethiolate ligand.
      Molecules of this compound interact through a set of N-H...(Me)O-H...S hydrogen
      bonds with methanol hydroxyl group being simultaneously acceptor and donor. With
      2-methylimidazole the product is an assembly of two different neutral complexes
      joined again by hydrogen bonds, however, this time of N-H...S type. One of these
      complexes has the previously mentioned MnO(2)NS(2) core. The second neutral
      complex exhibits four donor atoms (MnNOS(2)core) derived from four independent
      ligands, i.e., two silanethiolate rests, one N-heterocyclic base and one alcohol.
      This structure presents similarities with a zinc-based alcohol dehydrogenase
      active site that have never been obtained before, including with other metals
      (Zn, Co). It may, therefore, be considered the first neutral structural model of
      liver alcohol dehydrogenase (LADH).

PMID- 17234271
TI  - Rapid detection of CAA/CAG repeat polymorphism in the AIB1 gene using DHPLC.
AB  - Denaturing high-performance liquid chromatography (DHPLC) has been used for rapid
      and accurate DNA mutation analysis; to extend the DNA fragment lengths analysis.
      Recently, polymorphism in polyglutamine-coding region of Amplified In Breast
      cancer gene 1 (AIB1) was analyzed as an independent genetic risk factor
      influencing breast cancer onset in carriers of mutation in breast cancer
      predisposing gene 1 (BRCA1). We have implemented efficient, cost-effective and
      rapid method for analysis of the AIB1 polyglutamine repeat polymorphism based on
      DHPLC analysis (WAVE system) of unlabeled PCR products. This strategy can be
      useful for genotyping of other trinucleotide repeat polymorphisms using DHPLC in
      medium/high throughput settings.

PMID- 17234273
TI  - Rodent models: utility for candidate gene studies in human attention-deficit
      hyperactivity disorder (ADHD).
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioral
      disorder defined by symptoms of developmentally inappropriate inattention,
      impulsivity and hyperactivity. Behavioral genetic studies provide overwhelming
      evidence for a significant genetic role in the pathogenesis of the disorder.
      Rodent models have proven extremely useful in helping understand more about the
      genetic basis of ADHD in humans. A number of well-characterized rodent models
      have been proposed, consisting of inbred strains, selected lines, genetic
      knockouts, and transgenic animals, which have been used to inform candidate gene
      studies in ADHD. In addition to providing information about the dysregulation of
      known candidate genes, rodents are excellent tools for the identification of
      novel ADHD candidate genes. While not yet widely used to identify genes for ADHD
      like behaviors in rodents, quantitative trait loci (QTL) mapping approaches using
      recombinant inbred strains, heterogeneous stock mice, and chemically mutated
      animals have the potential to revolutionize our understanding of the genetic
      basis of ADHD.

PMID- 17234274
TI  - Testing the tripartite model in young adolescents: is hyperarousal specific for
      anxiety and not depression?
AB  - BACKGROUND: To clarify the distinction between anxiety and depression, the
      tripartite model was introduced. According to this model, physiological
      hyperarousal (PH, i.e. autonomic hyperactivity) is specific for anxiety and not
      depression. Research on the relation between anxiety, depression and
      physiological measures representing arousal is lacking. METHODS: Parent- and self
      reported anxiety and depressive problems were assessed using the CBCL and RCADS.
      Heart rate (HR), heart rate variability in the low frequency (HRV LF) and
      respiratory sinus arrythmia (RSA) were used as indices for autonomic arousal.
      RESULTS: Parent-reported anxiety was associated with low RSA in supine posture.
      This association was also found for self-reported anxiety problems, but only in
      boys. These findings point towards high arousal in anxiety. Self-reported
      depressive problems were associated with low HRV LF in standing posture and high
      RSA in supine posture in boys, pointing towards low arousal in depression.
      However, self-reported depressive problems were also associated with high HR in
      standing posture and with low HRV LF in supine posture in girls, suggesting high
      arousal in depression. LIMITATIONS: Although HRV LF in standing posture is
      primarily sympathetically mediated, and HRV LF in supine posture is primarily
      vagally mediated, the association between HRV LF and sympathetic versus vagal
      function is not exclusive. Thus, HRV LF measures are merely approaches of high or
      low arousal. CONCLUSIONS: Some evidence was found for hyperarousal in anxiety,
      but also for hyperarousal in depression. Apparently, the idea of hyperarousal in
      anxiety and not in depression is too simple to reflect the more complex reality.

PMID- 17234275
TI  - Global warming possibly linked to an enhanced risk of suicide: data from Italy,
      1974-2003.
AB  - BACKGROUND: The global increase in surface temperature (known as global warming)
      was found to impact on mortality through ill health, particularly among the
      elderly and in summer. This study sets out to explore the impact of global
      warming on suicide mortality, using data from Italy. METHODS: Monthly data on
      suicide mortality and temperature were obtained for a 30-year period (from
      January 1974 to December 2003), and the relation between them was investigated
      using the Gaussian low-pass filter, linear correlation analysis and rank
      analysis. RESULTS: For males, increasing anomalies in monthly average
      temperatures associated to a higher monthly suicide mean from May to August and,
      to a lower extent, in November and December. In January, on the other hand,
      increasing anomalies in monthly average temperatures appeared to be coupled to a
      lower number of suicides. For females, the links between temperature and suicides
      are less consistent than for males, and sometimes have a reverse sign, too.
      LIMITATIONS: Data could not be analyzed according to age, since this information
      was not available across the whole time interval. The use of monthly data,
      instead of daily data (unavailable), is another major limitation of this study.
      CONCLUSIONS: An improvement in the ability of communities to adjust to
      temperature changes by implementing public health interventions may play an
      important part in preserving the wellness of the general population, and also in
      limiting the worst consequences of suicidal behaviour.

PMID- 17234276
TI  - Prior facial motor neuron injury elicits endogenous T cell memory: relation to
      neuroregeneration.
AB  - We tested the hypotheses that prior injury to the facial motor nucleus (FMN)
      would elicit a more robust T cell response in the opposite FMN when the
      contralateral facial nerve was injured later in life, and that this would result
      in improved neuroregeneration. Measures of T cell, neuronal and microglial status
      were compared in sensitized mice (right facial nerve transection followed by
      contralateral facial nerve transection 9.5 weeks later) and naive mice (sham
      surgery of the right facial nerve followed by contralateral facial nerve
      transection 9.5 weeks later) following axotomy of the contralateral facial nerve.
      At day 14 post-axotomy, sensitized mice exhibited nearly a two-fold increase in T
      cells in the FMN compared to naive mice. There were no differences between the
      groups in levels of dead neurons and NeuN expression by surviving motor neurons
      at day 14, or motor neuron survival and cell area at day 49 post-axotomy.
      Measures of microglial responsiveness did not differ between the groups. Further
      study is needed to delineate the role of endogenous T cell memory in neuronal
      injury and regeneration.

PMID- 17234277
TI  - Hippocampal long-term depression: master or minion in declarative memory
      processes?
AB  - The neural mechanisms for the formation of declarative memory (memory for facts
      and events) are believed to be integrated from processes mediated by hippocampal
      long-term potentiation (LTP) and long-term depression (LTD). Traditionally, LTP
      has been designated as the main mediator of spatial memory storage in the
      hippocampus, whereas LTD has been assigned an auxiliary role in signal-to-noise
      regulation or in forgetting. It has recently become apparent, however, that LTD
      contributes directly to hippocampal information storage. In fact, LTD could
      dominate in the processing of precise spatial characteristics. Accumulating
      evidence supports the idea that LTP and LTD enable distinct and separate forms of
      information storage, which together facilitate the generation of a spatial
      cognitive map.

PMID- 17234278
TI  - Assessment of Caenorhabditis elegans as a model in Haemonchus contortus vaccine
      research.

PMID- 17234279
TI  - Lessons from the gastrin knockout mice.
AB  - The gastrointestinal hormone, gastrin, was discovered a century ago as the second
      hormone in history. Subsequently, gastrin peptides have been identified and the
      genes encoding the hormone as well as its receptor have been cloned in several
      mammalian species including the mouse. This has facilitated the development of
      gastrin and gastrin receptor deficient mice as models for genetic dissection of
      the role of gastrins in maintaining gastric homeostasis and control of acid
      secretion. The gastrin knockout mice are achlorhydric due to inactivation of the
      ECL and parietal cells. Moreover, this achlorhydria is associated with the
      development of intestinal metaplasia and bacterial overgrowth, which ultimately
      lead to development of gastric tumors. Outside the stomach, gastrin deficiency
      alters pancreatic islet physiology and is associated with a moderate fasting
      hypoglycemia in the fasting state. But lack of gastrin does not impair islet
      regeneration. The association between progastrin, progastrin-derived processing
      intermediates and colorectal carcinogenesis has also been examined through
      genetic or chemical cancer induction in several mouse models, although the
      clinical relevance of these studies still remains to be proven. While others have
      focused on models of increased gastrin production, the present review will
      describe the lessons learned from the gastrin deficient mice. These mice help
      understand how dysregulation of gastrin secretion may be implicated in human
      disease.

PMID- 17234280
TI  - Local vascular dysfunction after coronary paclitaxel-eluting stent implantation.
AB  - BACKGROUND: Paclitaxel-eluting stents (PES) have been shown to reduce the rate of
      restenosis and the need for repeated revascularization procedures compared with
      bare metal stents. However, long-term effects of paclitaxel on vascular function
      are unknown. The purpose of the present study was to assess coronary vasomotor
      response to exercise after paclitaxel-eluting stent implantation. METHODS:
      Coronary vasomotion was evaluated by biplane quantitative coronary angiography at
      rest and during supine bicycle exercise in 27 patients with coronary artery
      disease. Twelve patients were treated with a bare metal stent (controls), and
      fifteen patients with a paclitaxel-eluting stent. All patients were restudied 6+/
      2 (range 2-12) months after stent implantation. Minimal luminal diameter, stent
      diameter, proximal, distal and a reference vessel diameter were determined.
      RESULTS: Reference vessels showed exercise-induced vasodilation in both groups
      (+20+/-5% controls; +26+/-3% PES group). Vasomotion within the stented vessel
      segments was abolished. In the controls, the adjacent segments proximal and
      distal to the stent showed exercise-induced vasodilation (+17+/-3% and +24+/-4%).
      In contrast, there was exercise-induced vasoconstriction of the proximal and
      distal vessel segments adjacent to the paclitaxel-eluting stent (-13+/-6% and 
      18+/-4%; p<0.005). After sublingual nitroglycerin, the proximal and distal vessel
      segments dilated in both groups. Exercise-induced vasoconstriction adjacent to
      paclitaxel-eluting stent correlated inversely with the time interval after stent
      implantation. CONCLUSIONS: Paclitaxel-eluting stent implantation is associated
      with exercise-induced vasoconstriction in the persistent region suggesting
      endothelial dysfunction as the underlying mechanism. Improvement of vascular
      function occurs over time, indicating delayed vascular healing.

PMID- 17234281
TI  - Plasma concentrations of asymmetric dimethylarginine (ADMA) in metabolic
      syndrome.
AB  - Elevated circulating ADMA levels have been proposed as the pivotal link between
      insulin resistance, cardiovascular disease, and endothelial dysfunction in
      Caucasian population. To evaluate whether there is an association between plasma
      ADMA concentrations and insulin resistance in Hispanic population, we identified
      metabolic syndrome NCEP-ATP III criteria and measured ADMA and L-arginine plasma
      concentrations in 147 Colombian young males consecutively included in a cross
      sectional study. In contrast to inflammatory markers, ADMA was not found to be
      elevated in subjects with metabolic syndrome, furthermore, no significant
      association between ADMA concentrations and insulin resistance degree was found.
      In conclusion, our results suggest that at least in our population, ADMA does not
      seem to be implicated in the pathophysiology of metabolic syndrome. Ethnic
      specific or environmental differences in the etiologic mechanisms of metabolic
      syndrome need to be elucidated in further studies.

PMID- 17234282
TI  - Unemployment and deprivation are associated with a poorer outcome following
      percutaneous coronary angioplasty.
AB  - This prospective observational study aimed to assess the impact of employment
      status and deprivation on quality of life 12 months after percutaneous coronary
      intervention (PCI). Patients completed a questionnaire at baseline and at 1 year
      follow-up including a health utility score (EQ-5D), symptoms and employment
      status. Deprivation was assessed using the Carstairs' deprivation category based
      on area postcodes. The majority (79.6%) of patients of working age returned to
      work within 12 months. Unemployment was associated with a lower quality of life
      (QoL) at baseline (0.49 (0.32) vs 0.61 (0.27), p=0.002) and less improvement in
      QoL 1 year after PCI (0.15 (0.37) vs 0.26 (0.31), p<0.012). Furthermore,
      unemployed patients had significantly less improvement in chest pain score
      (p=0.002) and breathlessness (p<0.001). Unemployed patients from the most
      deprived areas had lowest QoL at follow-up and least improvement in QoL at 1
      year. Unemployment and deprivation are associated with poorer outcomes following
      PCI.

PMID- 17234283
TI  - Stents can jump!
AB  - Stent dislodgment or embolisation of a stent before deployment is a well known
      but feared problem in interventional cardiology with hazardous potential for the
      patient. Typically, dislodged stents are found in the treated vessel or embolise
      to the systemic circulation. Embolisation of an undeployed stent from one
      coronary artery to another has never been reported before. Knowledge and early
      recognition of this complication is mandatory because of its possible major
      clinical implications.

PMID- 17234284
TI  - D-dimer and BNP levels in acute aortic dissection.
AB  - Early diagnosis and treatment are pivotal for patients with acute aortic
      dissection (AAD). D-dimer is a rule-out diagnostic test for pulmonary embolism
      but there is evidence that it may also be applicable to AAD. We evaluated plasma
      D-dimer, white cell blood count (WBC), C-reactive protein (CRP) and N-terminal
      pro-B-type natriuretic peptide (BNP) in 18 consecutive patients with established
      AAD, 21 consecutive patients with dilated ascending aortas scheduled for elective
      surgery and 8 normal subjects. Patients with AAD had significantly higher
      elevated D-dimer, compared to chronic aneurysms and normal controls (p<0.0001). D
      dimer level higher than 700 ng/ml had a sensitivity of 94% and specificity of 59%
      for diagnosis of AAD. The WBC count was also significantly increased compared to
      the other groups (p<0.01). CRP and BNP values were significantly higher compared
      to normal controls but these parameters did not distinguish between AAD and
      chronic aneurysms. D-dimer can be used as a 'rule-out' test in patients with
      suspected AAD and seems useful in the discrimination between AAD and chronic
      uncomplicated aneurysms, unlike CRP and BNP plasma levels.

PMID- 17234285
TI  - Focal fibrosis in the left ventricle of subjects with cardiac amyloidosis
      evaluated by multislice computed tomography.
AB  - Cardiac amyloidosis is generally a progressive disease with a poor prognosis, so
      early diagnosis and appropriate treatments are important. Although cardiac
      amyloidosis can be diagnosed definitively by endomyocardial biopsy, non-invasive
      methods of diagnosis are desired because of a great risk in biopsy. In ECG-gated
      enhanced multislice computed tomography, not only clear images of the cardiac
      morphology but also the character of myocardium indicating fibrosis can be
      identified. We demonstrate two patients with cardiac amyloidosis who showed
      marked thickening of left ventricular wall with partial fibrotic changes by
      enhanced multislice computed tomography.

PMID- 17234286
TI  - Outlet type of interventricular septal defect in SanFilippo type-B syndrome.
AB  - Mucopolysaccharidoses (MPS) are a heterogeneous group of lysosomal storage
      disorders, due to deficiency of glycosaminoglycans breakdown enzymes. MPS type
      III is also known as SanFilippo syndrome, which is further subdivided into four
      distinct forms--A, B, C and D--caused by different enzyme deficiencies, but with
      similar clinical characteristics. Cardiac involvement in SanFilippo syndrome is
      less common compared with the other MPS types. In our case report, outlet type of
      interventricular septal defect was echocardiographically diagnosed in a fifteen
      year-old boy with known history of SanFilippo type-B syndrome, which, to our
      knowledge, has not yet been reported.

PMID- 17234287
TI  - A new cultivation independent approach to detect and monitor common Trichoderma
      species in soils.
AB  - A set of primers was developed for the detection, identification and
      quantification of common Trichoderma species in soil samples. Based on a broad
      range master alignment primers were derived to amplify an approximate 540 bp
      fragment comprising the internal transcribed spacer region 1 (ITS 1), 5.8S rDNA
      and internal transcribed spacer region 2 (ITS 2) from all taxonomic Clades of the
      genus Trichoderma. The primer set was applied to test strains as well as
      community DNA isolated from arable and forest soil. For all tested isolates the
      corresponding internal transcribed spacer regions of Trichoderma spp. strains
      were amplified, but none of non-Trichoderma origin. PCR with community DNA from
      soil yielded products of the expected size. Analysis of a clone library
      established for an arable site showed that all amplified sequences originated
      exclusively from Trichoderma species mainly being representatives of the Clades
      Hamatum, Harzianum and Pachybasioides and comprising most of the species known
      for biocontrol ability. In a realtime PCR approach the primer set uTf/uTr also
      proved to be a suitable system to quantify DNA of Trichoderma spp. in soils.

PMID- 17234288
TI  - Industrial biotechnology for the production of bio-based chemicals--a cradle-to
      grave perspective.
AB  - Shifting the resource base for chemical production from fossil feedstocks to
      renewable raw materials provides exciting possibilities for the use of industrial
      biotechnology-based process tools. This review gives an indication of the current
      developments in the transition to bio-based production, with a focus on the
      production of chemicals, and points out some of the challenges that exist in the
      large-scale implementation of industrial biotechnology. Furthermore, the
      importance of evaluating the environmental impact of bio-based products with
      respect to their entire life cycle is highlighted, demonstrating that the choice
      of the raw material often turns out to be an important parameter influencing the
      life cycle performance.

PMID- 17234289
TI  - Scent engineering: toward the goal of controlling how flowers smell.
AB  - Floral scent has an important role in the reproductive processes of many plants
      and a considerable economic value in guaranteeing yield and quality of many
      crops. It also enhances the aesthetic properties of ornamental plants and cut
      flowers. Many floral scent volatiles fall into the terpenoid or
      phenylpropanoid/benzenoid classes of compounds. Although the biochemistry of
      floral scent is still a relatively new field of investigation, in the past decade
      investigators have begun to identify 'scent genes'. Several of these genes, most
      of which, but not all, encode enzymes that directly catalyze the formation of
      volatile terpenoid or phenylpropanoid/benzenoid compounds, have now been used to
      manipulate, through genetic engineering techniques, the mix of volatiles emitted
      from the flowers of several plant species. The outcomes of these experiments,
      which are discussed here, have indicated that the genetic engineering approach to
      altering floral scents has potential; however, they have also revealed the
      limitations that result from our inadequate knowledge of the metabolic pathways
      responsible for scents and their regulation.

PMID- 17234290
TI  - Impaired updating of working memory in schizophrenia.
AB  - This study investigated working memory in schizophrenia, using an auditory target
      detection task specifically designed to separate out brain activity related to
      the updating of working memory with new information from activity related to
      target detection and response. Event related potentials (ERPs) were recorded
      during task performance, using 31 electrodes, from 25 subjects with schizophrenia
      and 25 matched controls. Subjects with schizophrenia had a reduction in parietal
      P3 and Late Slow Wave amplitude in the ERP waveforms recorded when the task
      required subjects to remember a new stimulus. This P3 amplitude attenuation
      correlated with symptom measures of preoccupation and poor volition. Previous
      findings of a reduction in P3 amplitude during target detection by subjects with
      schizophrenia were replicated. These results suggest that there is a specific
      impairment in the ability to update working memory in schizophrenia, and that
      this is associated with poverty of engagement with the environment.

PMID- 17234291
TI  - Entropy changes in brain function.
AB  - The traditional way of analyzing brain electrical activity, on the basis of
      electroencephalography (EEG) records, relies mainly on visual inspection and
      years of training. Although it is quite useful, of course, one has to acknowledge
      its subjective nature that hardly allows for a systematic protocol. In the
      present work quantifiers based on information theory and wavelet transform are
      reviewed. The "relative wavelet energy" provides information about the relative
      energy associated with different frequency bands present in the EEG and their
      corresponding degree of importance. The "normalized total wavelet entropy"
      carries information about the degree of order-disorder associated with a multi
      frequency signal response. Their application in the analysis and quantification
      of short duration EEG signals (event-related potentials) and epileptic EEG
      records are summarized.

PMID- 17234292
TI  - Family history of cardiovascular disease is associated with cardiovascular
      responses to stress in healthy young men and women.
AB  - Heightened cardiovascular stress responsivity is associated with cardiovascular
      disease, but the origins of heightened responsivity are unclear. The present
      study investigated whether disturbances in cardiovascular responsivity were
      evident in individuals with a family history of cardiovascular disease risk. Data
      were collected from 60 women and 31 men with an average age of 21.4 years. Family
      history of cardiovascular disease risk was defined by the presence of coronary
      heart disease, hypertension, diabetes or high cholesterol in participants'
      parents and grandparents; 75 participants had positive, and 16 had negative
      family histories. Systolic and diastolic blood pressure (BP), heart rate and
      heart rate variability were measured continuously for 5 min periods at baseline,
      during two mental stress tasks (Stroop and speech task) and at 10-15 min, 25-30
      min and 40-45 min post-stress. Individuals with a positive family history
      exhibited significantly greater diastolic BP reactivity and poorer systolic and
      diastolic BP recovery from the stressors in comparison with family history
      negative individuals. In addition, female participants with a positive family
      history had heightened heart rate and heart rate variability reactivity to
      stressors. These effects were independent of baseline cardiovascular activity,
      body mass index, waist to hip ratio and smoking status. Family history of
      hypertension alone was not associated with stress responsivity. The findings
      indicate that a family history of cardiovascular disease risk influences stress
      responsivity which may in turn contribute to risk of future cardiovascular
      disorders.

PMID- 17234293
TI  - The effect of calcium ions on adhesion and competitive exclusion of Lactobacillus
      ssp. and E. coli O138.
AB  - The adhesion abilities of 11 strains of Lactobacillus were determined in vitro
      using the IPEC-J2 cell line as a model system. Bacteria cultures included the
      probiotic strains L. rhamnosus GG, L. reuteri ATCC 55730, L. johnsonii NCC 533
      and L. reuteri DSM 12246, and new isolates of Lactobacillus ssp. Adhesion was
      quantified by scintillation counting of radiolabelled bound bacteria. The highest
      adhesion of 38%, was determined for L. reuteri DSM 12246 followed by L. plantarum
      Q47 with an adhesion level of 24%. Other strains showed moderate to low binding
      of less than 16%. Competitive adhesion experiments on IPEC-J2 cells demonstrated
      that strongly adhesive strains, as L. reuteri DSM 12246 and L. plantarum Q47,
      significantly reduced the attachment of the less adhesive strains, such as L.
      rhamnosus GG and L. johnsonii NCC 533, both under condition of co-incubation and
      in displacement assays, indicating that bacteria may share the same binding sites
      for attachment to intestinal cells. Furthermore, it was revealed that calcium
      ions significantly increased the binding of tested lactobacilli to IPEC-J2 cells;
      and therefore, added calcium may be useful in enhancing the adhesion of normally
      weakly adhesive probiotic cultures. In contrast, no significant change in
      adhesion of lactobacilli was observed in the presence of Mg and Zn ions.
      Displacement assays performed with pathogenic E. coli O138 showed that all tested
      Lactobacillus strains reduced the attachment of E. coli O138 to IPEC-J2 by more
      than 2-fold both in the presence and the absence of calcium ions. The strains of
      Lactobacillus did not differ significantly in the extent of their inhibition of
      E. coli O138 adhesion, indicating that the reduced adhesion of E. coli O138 was
      due to steric hindrance of the binding sites rather than to specific
      interactions.

PMID- 17234294
TI  - Counteracting expression deficiencies by anticipating posttranslational
      modification of PaHNL5-L1Q-A111G by genetic engineering.
AB  - (R)-2-chloromandelic acid represents a key pharmaceutical intermediate. Its
      production on large scale was hampered by low turnover rates and moderate
      enantiomeric excess (ee) using enzyme as well as metal catalysts. The cloning and
      heterologous overexpression of an (R)-hydroxynitrile lyase from Prunus amygdalus
      opened a way to large-scale production of this compound. Especially the
      rationally designed mutation of alanine to glycine at amino acid position 111 of
      the mature protein tremendously raised the yield for enantioselective conversion
      of 2-chlorobenzaldehyde to (R)-2-chloromandelonitrile, which can be hydrolysed to
      the corresponding alpha hydroxy acid. However, expression of this mutein was less
      efficient than for the unmodified enzyme. Subsequent LC/MS/MS-analysis of the
      protein sequence revealed that mutation A111G triggered the posttranslational
      deamidation of the neighbouring residue asparagine (N110) to aspartic acid. This
      finding on the one hand could explain the decreased secretion efficiency of the
      mutant as compared to the wildtype enzyme, but on the other hand raised the
      question which of the two residues was truly accountable for the enhanced
      conversion. The muteins N110D, A111G and N110DA111G were constructed and compared
      in terms of protein productivity and performance in chemical syntheses. The
      expression level of the double mutein was augmented significantly and the
      enantioselectivity remained high. Reduced protein expression of mutein PaHNL5-L1Q
      A111G was remedied by mutational anticipation of posttranslational deamidation.

PMID- 17234295
TI  - Nanosuspensions of alendronate with gallium or gadolinium attenuate neointimal
      hyperplasia in rats.
AB  - Monocytes/macrophages play a pivotal role in the formation of neointinal
      hyperplasia following vascular injury. Transient depletion of circulating
      monocytes by particulate delivery systems containing bisphosphonates, such as
      alendronate, results in restenosis inhibition. We hypothesized that a self
      suspendable nanoparticulate dosage form, with a minimum amount of expients, could
      be formulated by complexing the negatively charged alendronate with gallium or
      gadolinium. We further hypothesized that a synergistic biological effect could be
      obtained by nanosuspensions of alendronate with these counter ions.
      Nanosuspensions (150-250 nm) of alendronate-gallium and alendronate-gadolinium
      were successfully formulated with no additives except for the active agents and
      HCl for pH adjustment. Both nanosuspensions exhibited macrophage cell line growth
      inhibition in a dose-response relationship in comparison to the various agents in
      solution and in liposomes. A synergistic effect of the nanosuspensions was
      observed in the inhibition of raw264 macrophages, and in reducing IL-1beta and
      TNF-alpha secretion in cell culture. Single IV administration at the time of
      injury, of alendronate-gallium or alendronate-gadolinium nanosuspensions resulted
      in inhibition of neointimal hyperplasia and stenosis in the rat model of vascular
      injury. The results correlated with the significant reduction of circulating
      monocytes. The nanosuspensions possess the advantages of no additives for minimal
      provocation of side effects, and the potential of immunomodulating inflammatory
      disorders.

PMID- 17234296
TI  - Equivalent insulin resistance in latent autoimmune diabetes in adults (LADA) and
      type 2 diabetic patients.
AB  - Insulin resistance is a primary component in the pathophysiology of type 2
      diabetes. In latent autoimmune diabetes in adults (LADA), insulin resistance has
      been reported to be significantly lower than in autoantibody-negative type 2
      diabetes (T2DM), but whether this might be related to differences in body mass
      index (BMI) has not been excluded. Furthermore, previous studies have used
      limiting inclusive criteria for LADA, requiring only the presence of GADA or IA
      2A. To apply more inclusive criteria for LADA, consistent with recent
      recommendations, we defined LADA by clinical manifestations characteristic of
      T2DM, but with the presence of any combination of GADA, IA-2A, ICA, or IAA. We
      recruited 43 LADA patients, 70 T2DM patients, and 150 non-diabetic controls.
      Insulin resistance was assessed by both the homeostasis model assessment and the
      quantitative insulin sensitivity check index, and BMI was calculated. We found
      that insulin resistance in LADA is equivalent to that of T2DM. When insulin
      resistance is assessed as a function of BMI, both diabetic populations
      demonstrated an insulin resistance equally greater than normal controls. The
      interaction between insulin resistance and BMI in the two diabetic groups was
      significantly different from that demonstrated in non-diabetic controls. In
      summary, LADA demonstrates insulin resistance of similar magnitude to T2DM, but
      with the concurrent component of an immune attack against the pancreatic beta
      cells. LADA patients may be at significant risk for metabolic consequences of
      insulin resistance other than glucose metabolism, such as those described in the
      metabolic syndrome. As complications and treatment regimens specific to LADA are
      realized, improved means of identification of LADA will become increasingly
      important.

PMID- 17234297
TI  - Continuous glucose monitoring versus self-monitoring of blood glucose in the
      treatment of gestational diabetes mellitus.
AB  - OBJECTIVE: To compare Continuous Glucose Monitoring System (CGMS) with self
      monitoring of plasma glucose (SM) in detecting patients with gestational diabetes
      mellitus (GDM) needing antidiabetic drug treatment. RESEARCH DESIGN AND METHODS:
      Pregnant women at 22-34 gestational weeks had at least two abnormal high values
      out of three in OGTT. Patients were randomly allocated to have CGMS) (n=36) or SM
      (n=37). Dietary counselling was similar in both groups. Patients tested their
      plasma glucose 5 times per day. Need of antidiabetic treatment was determined
      using the following cut-off values: fasting plasma glucose >5.5mmol/L twice or
      >5.5mmol/l once and postprandial value>7.8mmol/l, or postprandial value at least
      twice above 7.8mmol/l. RESULTS: In 11 out of 36 patients (31%) monitored with
      CGMS) antihyperglycemic drug therapy was introduced (8/36 insulin only, 2/36
      metformin only, 1/36 insulin+metformin) whereas only 3/37 (8%) in the self
      monitoring group were drug-treated (difference between groups, p=0.0149). There
      were no statistically significant differences between the groups regarding
      maternal age, pre-pregnancy BMI, HbA1c, gestational weeks at delivery, rate of
      pregnancy-induced hypertension, rate of caesarean section, infant birth weight or
      neonatal hypoglycaemia. CONCLUSIONS: Continuous glucose monitoring system detects
      a markedly higher proportion of GDM mothers needing antihyperglycemic medication
      compared with self-monitoring of plasma glucose. Further large-scale studies are
      needed to evaluate whether CGMS) guided initiation of antihyperglycemic therapy
      results in less macrosomia and perinatal complications related to GDM.

PMID- 17234298
TI  - Serum C-reactive protein levels correlates better to metabolic syndrome defined
      by International Diabetes Federation than by NCEP ATP III in men.
AB  - The International Diabetes Federation (IDF) proposed a new definition for
      metabolic syndrome (MS) in 2005. We conducted this study to compare the
      association of MS by IDF and ATP III definition to various metabolic variables.
      In 2005, we enrolled 654 Chinese people in a screening program in Taiwan.
      Anthropometric and biochemical profiles, including high-sensitivity C-reactive
      protein (hsCRP), were measured. Serum hsCRP levels were higher in those with MS
      by IDF definition (2.4+/-1.9mg/l versus 1.3+/-1.4mg/l, p<0.0001). Serum hsCRP
      levels increase with the number of components of MS they met (p for trend<0.001).
      Serum LDL levels were higher in those with MS by IDF definition (131+/-39 versus
      125+/-32, p<0.05) but not in those with MS by ATP III definition (p=0.2). Serum
      hsCRP levels correlate significantly to MS by ATP III definition, after adjusting
      for age, sex, smoking, body mass index, serum apolipoprotein A1 and LDL levels.
      Adding MS status by IDF definition in this model significantly increased model
      fitness in men (MS by IDF definition, partial r=0.18, p<0.05, MS by ATP III
      definition, partial r=0.12, p=0.071). In conclusion, IDF definition of MS has a
      stronger relationship with serum hsCRP than ATP III definition in men.

PMID- 17234299
TI  - Prevalence of metabolic syndrome in Iranian adult population, concordance between
      the IDF with the ATPIII and the WHO definitions.
AB  - BACKGROUND: Different criteria have been proposed by the WHO, the ATPIII and the
      International Diabetes Federation (IDF) for the diagnosis of the metabolic
      syndrome (MES). The objective of this study was to estimate the prevalence of
      this syndrome using the IDF definition among Iranian adults and to compare it
      with the prevalence estimated using the two other definitions. MATERIALS AND
      METHODS: The prevalence of the MES was determined according to the three
      different proposals in 10,368 men and women aged >/=20 years participated in the
      cross-sectional phase of the Tehran Lipid and Glucose Study. To assess the degree
      of agreement between different MES definitions, the k test was used. RESULTS: The
      prevalence of MES (95% confidence interval) was 32.1% (31.2-33.0) by the IDF
      definition, 33.2% (32.3-34.1) by the ATPIII and 18.4% (17.6-19.2) according to
      the WHO definition. The sensitivity, specificity of the IDF definition for
      detecting MES were 91%, 89% for the ATPIII and 73%, 77% for the WHO definition,
      respectively. The k statistics for the agreement of the IDF definition was 66.3+/
      0.01 with the ATPIII and 39.5+/-0.01 with the WHO definition. CONCLUSION: In the
      Iranian population, the IDF definition for MES has a good concordance with the
      ATP III definition and a low concordance with the WHO definition.

PMID- 17234300
TI  - Alteration of NPY and Y1 receptor in dorsomedial and ventromedial areas of
      hypothalamus in anorectic tumor-bearing rats.
AB  - Although previous studies have implicated NPY in the etiology of experimental
      cancer anorexia, the results have been difficult to interpret. Studies have
      suggested that although NPY level and message were decreased in the dorsomedial
      hypothalamic area (DMA), they were elevated in the ventromedial hypothalamic area
      (VMA). To better assess specific intra-area alterations of NPY, Y(1) receptor
      (Y(1) R), and agouti-related peptide (AgRP) in TB rats, we used radioimmunoassay,
      quantitative real-time RT-PCR, and immunohistochemistry. We found that NPY and
      AgRP mRNA were elevated significantly in whole hypothalamus of anorectic TB rats,
      while Y(1) R mRNA was decreased. Based on two replicates of four pooled samples
      each, both NPY and AgRP mRNA appeared to be elevated in the VMA of anorectic TB
      rats, while only AgRP exhibited a similar increase in the DMA. Levels of NPY were
      elevated in the VMA of both TB and pair-fed (PF) rats, but in the DMA only PF
      rats exhibited a significant NPY increase. NPY and Y(1) R immunohistochemistry
      revealed reduced NPY staining in PVN and ARC nucleus of TB and PF rats. Y(1) R
      immunostaining was also reduced in the ARC and PVN of TB rats, while PF rats
      exhibited elevated immunostaining in the PVN. These results continue to implicate
      dysfunction of NPY feeding systems in experimental cancer anorexia and suggest
      down-regulation of Y(1) R receptors as well as possible problems in NPY
      translation.

PMID- 17234301
TI  - NPY and pain as seen from the histochemical side.
AB  - The expression of neuropeptide tyrosine (NPY) and two of its receptors (Y1- and
      Y2Rs) in different types of rodent dorsal root ganglion (DRG) and spinal cord
      neurons, and their regulation by peripheral nerve injury, have suggested a role
      in neuropathic pain. Here we present the spinal NPYergic system from an
      immunohistochemical perspective based on recent studies using two specific
      antibodies recognizing the Y1- and Y2Rs, respectively, as well as on data from a
      study on a Y1R knock-out mouse. We have, for example, defined seven different
      neuron populations of Y1R-expressing neurons in the rat spinal cord, representing
      multiple targets for spinally released NPY. The differential distribution of NPY
      receptors probably explains both the pro- and antinociceptive effects of NPY
      previously reported in the literature. One system possibly responsible for
      antinociception is a group of Y1R-positive, presumably glutamatergic interneurons
      in the superficial dorsal horn laminae. We also discuss the possibility that NPY
      released within DRGs can act in a paracrine fashion on NPY receptors on adjacent
      neurons, perhaps contributing to the so-called cross excitation, a concept
      advanced by Devor, Amir and collaborators. Taken together with behavioral and
      electrophysiological results summarized by Smith et al. in this volume,
      histochemical analyses have advanced the knowledge on the role of NPY in pain
      processing.

PMID- 17234302
TI  - Association of prostaglandin-endoperoxide synthase 2 (PTGS2) polymorphisms and
      Alzheimer's disease in Chinese.
AB  - Cyclooxygenase-2 (COX-2, encoded by the gene prostaglandin-endoperoxide synthase
      2, PTGS2) is a key enzyme in the conversion of arachidonic acid to
      prostaglandins. The prostaglandins produced by COX-2 are involved in inflammation
      and pain response in different tissues in the body. Enhanced COX-2 expression had
      been found in regions of brains from patients with Alzheimer's disease (AD).
      Here, we proceeded to test the hypothesis that polymorphisms of the PTGS2 gene
      predispose to AD. IVS5-275 T>G and Ex10+837 T>C in addition to three tagging SNPs
      from HapMap database, which provided a comprehensive coverage of genetic
      variations in the PTGS2 gene in Chinese were genotyped among 257 AD patients and
      244 age-matched healthy Chinese subjects. Genetic associations were analyzed by
      chi(2)-test and haplotypes analysis. Although the previously reported protective
      polymorphism (rs20417, -765 G/C) for AD in PTGS2 gene was not polymorphic in the
      Chinese population, SNPs in both the promoter (-2319 G>T) and 3' region (Ex10+837
      T>C) of PTGS2 were associated with the risk of AD (p=0.01 and 0.03,
      respectively). Carriers of Ex10+837 T allele had a 1.5-fold increase in the risk
      of AD. This study suggested that PTGS2 gene was a predisposition gene and
      arachidonic acid metabolism might be involved in the pathogenesis of AD. It
      provided further evidence to support a role of inflammation in the development
      and progression of AD.

PMID- 17234303
TI  - Novel and versatile methodology for synthesis of cyclic imides and evaluation of
      their cytotoxic, DNA binding, apoptotic inducing activities and molecular
      modeling study.
AB  - Versatile method has been developed for synthesis of N-substituted imides. Thus,
      acid anhydrides, imides and dicarboxylic acids were successfully subjected to
      dehydrative cyclization with substituted amines using DPPOx and Et(3)N to afford
      N-substituted imides under mild conditions. The DNA binding and apoptosis
      induction were investigated with regard to their potential utility as cytotoxic
      agents. Molecular modeling methods are used to study the cytotoxic activity of
      the active compounds by means of molecular and quantum mechanics.

PMID- 17234304
TI  - Facing registration: the expectations and the unexpected.
AB  - This paper reports on newly qualified nurses' experiences of the transition from
      being a nursing student to becoming a registered nurse. The aim of the study was
      to ascertain how newly qualified nurses perceived their role transition in an
      Irish general hospital. Data were gathered using in-depth interviews with 12
      nurses who were within one year of qualification. A grounded theory approach was
      used to generate, analyse and synthesise the data. The findings revealed that
      newly qualified nurses have specific needs, many of which are unrealised. The
      vast and increased workload, which involved less patient-contact and more non
      nursing duties, came as a surprise to participants in this study. The expectation
      of in-depth knowledge, coupled with feelings of increased responsibility and
      compounded by relatively little experience did little to ease the transition to
      becoming a newly qualified nurse. There is a need to contextualise the transition
      to registration so that expectations of newly qualified nurses are realistic.
      Management and staff must remain cognisant of the fact that many newly registered
      nurses have relatively limited clinical experience at the time of registration.

PMID- 17234305
TI  - LEE-encoded regulator (Ler) mutants elicit serotype-specific protection, but not
      cross protection, against attaching and effacing E. coli strains.
AB  - We previously showed that single dose orogastric immunization with an attenuated
      regulatory Lee-encoded regulator (ler) mutant of the rabbit enteropathogenic
      Escherichia coli (REPEC) strain E22 (O103:H2) protected rabbits from fatal
      infection with the highly virulent parent strain. In the current study we
      assessed the degree of homologous (serotype-specific) and heterologous (cross
      serotype) protection induced by immunization with REPEC ler mutant strains of
      differing serotypes, or with a prototype strain RDEC-1 (O15:H-) which expresses a
      full array of ler up-regulated proteins. We constructed an additional ler mutant
      using RDEC-1 thus, permitting immunization with a ler mutant of either serotype,
      O15 or O103, followed by challenge with a virulent REPEC strain of the same or
      different serotypes. Consistent with our previous data, the current study
      demonstrated that rabbits immunized with a RDEC-1 ler mutant were protected from
      challenge with virulent RDEC-H19A (RDEC-1 transduced with Shiga toxin-producing
      phage H19A) of the same serotype. Rabbits immunized with RDEC-1 or E22 derivative
      ler mutants demonstrated significant increase in serum antibody titers to the
      respective whole bacterial cells expressing O antigen but not to the LEE-encoded
      proteins. However, immunization with the ler mutants of either E22 or RDEC-1
      failed to protect rabbits from infections with virulent organisms belonging to
      different serotypes. In contrast, rabbits immunized with the prototype RDEC-1
      were cross protected against challenge with the heterologous E22 strain as shown
      by normal weight gain, and the absence of clinical signs of disease or
      characteristic attaching and effacing (A/E) lesions. Immunization with RDEC-1
      induced significantly elevated serum IgG titers to LEE-encoded proteins. We thus,
      demonstrated homologous protection induced by the REPEC ler mutants and
      heterologous protection by RDEC-1. The observed correlation between elevated
      immune responses to the LEE-encoded proteins and the protection against challenge
      with heterologous virulent REPEC strain suggests that serotype-non-specific cross
      protection requires the expression of, and induction of antibody to, LEE-encoded
      virulence factors.

PMID- 17234306
TI  - GRA1 protein vaccine confers better immune response compared to codon-optimized
      GRA1 DNA vaccine.
AB  - The present study evaluates immunogenicity and protection potency of a codon
      optimized GRA1 DNA vaccine, wild type GRA1 DNA vaccine and an adjuvanted
      recombinant GRA1 protein vaccine candidate in BALB/c mice against lethal
      toxoplasmosis. Of the three GRA1 vaccines tested, the recombinant GRA1 protein
      vaccine results reveal significant increase in immune response and prolonged
      survival against acute toxoplasmosis compared to DNA vaccinations. Immune
      response and protection conferred by codon-optimized GRA1 DNA vaccine was
      slightly better than wild type GRA1 DNA vaccine.

PMID- 17234308
TI  - Results of a safety and immunogenicity study of an early-stage investigational
      rPA102 vaccine as compared to the FDA licensed anthrax vaccine (anthrax vaccine
      adsorbed (AVA. BioThrax)).

PMID- 17234307
TI  - Porcine enteric caliciviruses: genetic and antigenic relatedness to human
      caliciviruses, diagnosis and epidemiology.
AB  - Porcine enteric caliciviruses include sapoviruses and noroviruses. Porcine
      sapoviruses infect pigs of all ages and cause diarrhea in young pigs, whereas
      porcine noroviruses were detected exclusively from adult pigs without clinical
      signs. Importantly, certain porcine norovirus strains were genetically and
      antigenically related to human noroviruses. This raises public health concerns
      that pigs may be reservoirs for emergence of epidemic human norovirus strains.
      This article reviews the discovery of porcine noroviruses and sapoviruses, their
      classification, diagnosis, epidemiology and genetic and antigenic relatedness to
      human caliciviruses.

PMID- 17234309
TI  - The Canarypox-virus vaccine vector ALVAC triggers the release of IFN-gamma by
      Natural Killer (NK) cells enhancing Th1 polarization.
AB  - We investigated the mechanism by which ALVAC activates innate immunity. Combining
      ALVAC with protein antigens significantly augmented antigen-specific IgG2a
      responses; this was dependent on the presence of bioactive interferon (IFN)
      gamma. Immuno-depletion of NK cells prior to ALVAC immunisation abrogated IFN
      gamma production indicating that they are the main cellular source of early IFN
      gamma in vivo. Murine bone-marrow derived dendritic cells (BMDCs) cultured in the
      presence of ALVAC secreted high levels of the chemokines CXCL10 and CCL2 and up
      regulated expression of the maturation markers CD40, CD80 and CD86. Therefore, we
      conclude that ALVAC acts as an adjuvant through a mechanism requiring NK cell
      derived IFN-gamma, DC activation and chemokine secretion.

PMID- 17234311
TI  - The effect of flexor digitorum profundus quadriga on grip strength.
AB  - This study evaluated the flexor digitorum profundus quadriga effect by mimicking
      stiffness of one finger and observing its effect on the strengths of the other
      three fingers of the same hand. Thermoplastic wedges were used to simulate mild,
      moderate and severe stiffness of each finger and the individual strengths of each
      finger during power grip were measured using a digit-grip(TM) dynamometer in ten
      healthy adult volunteers. Middle, ring, and little fingers strength diminished
      significantly (P<0.05) when each of the other fingers, including the index, was
      stiffened. Index finger strength was largely unaffected by simulated stiffness of
      the other fingers. The degree of simulated stiffness influenced the strength of
      the other fingers, but there was considerable intersubject variability,
      suggesting that the significance of the quadriga effect varies between
      individuals. An anatomical basis for our findings is suggested.

PMID- 17234310
TI  - Animal-associated injuries and related diseases among returned travellers: a
      review of the GeoSentinel Surveillance Network.
AB  - BACKGROUND: Increased travel to exotic destinations around the world is
      escalating the risk of exposure to animal-associated injuries with a risk of
      acquiring rabies. METHODS: We have examined data reported to GeoSentinel
      Surveillance Network to highlight characteristics of animal-associated injuries
      in travellers. RESULTS: A total of 320 cases were reported from 1998 to 2005.
      Travellers were predominantly tourists from developed countries with median
      travel duration of 23 days. A pre-travel encounter was recorded in 45.0% of the
      cases. A significantly greater proportion of patients with animal-related
      injuries were female compared to other travel associated diagnosis (54.7% versus
      47.4%) and were most likely patients aged <15 years (6.2% versus 2.6%). The
      proportionate morbidity for sustaining an animal bite was higher among travellers
      visiting Southeast Asia (3.9%) and the rest of Asia (2.2%) compared to Australia
      New Zealand (1.9%), Africa (1.0%), Latin America (0.8%), North America (0.9%) and
      Europe (1.2%). Seventy-five percent of cases occurred in countries endemic for
      rabies. Dogs were involved in 51.3% of cases, monkeys in 21.2%, cats in 8.2%,
      bats in 0.7% and humans in 0.7%. The higher likelihood for animal-related
      injuries among female travellers was dependant on the animal species involved,
      with monkeys accounting for the majority of injuries. In contrast, males were
      more likely to be injured by dogs. Only 66.1% of all patients reported with
      animal-related injury received rabies post-exposure prophylaxis. CONCLUSIONS:
      This data shows that animal-associated injuries are not uncommon among returned
      travellers presenting to GeoSentinel sites. The highest proportion of injuries
      was recorded in travellers to Asia, mostly in regions, which are endemic for
      rabies, and this had led to a requirement for PEP.

PMID- 17234312
TI  - The flux of chloroform and tetrachloromethane along an elevational gradient of a
      coastal salt marsh, East China.
AB  - The fluxes of trichloromethane (CHCl(3), CM) and tetrachloromethane (CCl(4), TCM)
      were seasonally measured using static flux chambers over an annual cycle in a
      coastal salt marsh, East China. The salt marsh presented as a large sink for both
      the compounds in the growing season (from April to October), but it was a minor
      source for the gas species in the non-growing season. Generally, the cordgrass
      marsh acted as a sink of CM and TCM. The net consumption of CM and TCM observed
      in the study marsh may result from the high ambient atmospheric concentrations
      and enriched soil organic matter that result in anoxic sediments. Higher plants
      were suggested to be an important sink for CM and TCM in the growing season, but
      a net source in the non-growing season. However, the mechanism responsible for
      the plant removal process is not clear.

PMID- 17234313
TI  - The effect of earthworms on the fractionation and bioavailability of heavy metals
      before and after soil remediation.
AB  - The effect of two earthworm species, Lumbricus rubellus and Eisenia fetida, on
      the fractionation/bioavailability of Pb and Zn before and after soil leaching
      with EDTA was studied. Four leaching steps with total 12.5 mmol kg(-1) EDTA
      removed 39.8% and 6.1% of Pb and Zn, respectively. EDTA removed Pb from all soil
      fractions fairly uniformly (assessed using sequential extractions). Zn was mostly
      present in the chemically inert residual soil fraction, which explains its poor
      removal. Analysis of earthworm casts and the remainder of the soil indicated that
      L. rubellus and E. fetida actively regulated soil pH, but did not significantly
      change Pb and Zn fractionation in non-remediated and remediated soil. However,
      the bioavailability of Pb (assessed using Ruby's physiologically based extraction
      test) in E. fetida casts was significantly higher than in the bulk of the soil.
      In remediated soil the Pb bioavailability in the simulated stomach phase
      increased by 5.1 times.

PMID- 17234314
TI  - Partitioning of chloroaromatic compounds between the aqueous phase and dissolved
      and particulate soil organic matter at chlorophenol contaminated sites.
AB  - The retention and mobility of hydrophobic organic contaminants (HOCs) in soil is
      mainly determined by hydrophobic partitioning to dissolved and particulate
      organic matter (DOM and POM, respectively). The aqueous phase, DOM, and POM
      fractions were extracted and separated from soils at three sites contaminated
      with technical chlorophenol formulations. Concentrations of chlorophenols (CP),
      polychlorinated phenoxyphenols (PCPP), polychlorinated diphenyl ethers (PCDE) and
      polychlorinated dibenzo-p-dioxins and furans (PCDD/F) were determined. The
      partitioning to POM, in relation to DOM, increased in all three soils with
      increasing hydrophobicity in the order CP < PCPP ~ PCDE ~ PCDF < PCDD.
      Differences in partitioning to DOM (logK(DOC)) and POM (logK(POC)) could not be
      explained by differences in gross organic C chemistry. Black carbon did not
      contribute significantly to the sorption of PCDDs, whereas >70% wood fibre in one
      soil resulted in a decrease of logK(POC) of 0.5 units for CPs and PCDDs. We
      conclude that logK(OC) for both DOM and POM need to be explicitly determined when
      the retention and mobility of HOCs is described and modelled in soils.

PMID- 17234315
TI  - Comparative evaluation of acute toxicity of ivermectin by two methods after
      single subcutaneous administration in rats.
AB  - Ivermectin was evaluated for its acute toxicity after single subcutaneous (s/c)
      administration by 'Acute Toxic Class' method as per OECD 423 and by conventional
      acute toxicity test using probit analysis in rats. 'Acute toxic class' method
      yielded LD(50) in category 2 i.e. between 5 and 50mg/kg which was comparable with
      conventional method where it was found to be 51.5mg/kg. Post mortem lesions were
      observed in the form of congestion of liver, which showed centrilobar necrosis
      and hemorrhages on histopathological analysis in both the methods. This study
      suggests, 'Acute Toxic Class' method may be used instead of conventional method
      to study acute toxicity of injectable preparations. Similarly the LD(50) of
      around 50mg/kg indicated a wide margin of safety (250x) considering therapeutic
      dose of ivermectin as 200microg/kg.

PMID- 17234316
TI  - Intimate partner violence among Afghan women living in refugee camps in Pakistan.
AB  - The purpose of this paper is to explore events and factors that lead to conflict
      in the home in the Afghan refugee setting, and the current status of the health
      sector's ability to respond to evidence of conflict. Qualitative interviews were
      conducted with 20 women of reproductive age and 20 health workers serving these
      women in an Afghan refugee camp near Peshawar, Pakistan, during the summer of
      2004. In particular, this paper analyses women's explanations of how various
      marriage traditions may be linked to conflict in the home and how the
      interactions of different family members may be related to conflict. The
      relationships of women with their parents-in-law and husbands are highlighted in
      particular, and a model developed to explore the choreography of their
      relationships and the ways in which these dynamics may encourage or inhibit
      violence. The perspectives of health workers on the ways in which the health
      system responds to family conflict and violence are also presented. Finally, this
      paper provides information that helps to frame the issues of family violence and
      conflict in long-term refugee populations for intervention designers and those
      who are working to craft a health sector response to this problem.

PMID- 17234317
TI  - Health care for the poor--an exploration of primary-care physicians' perceptions
      of poor patients and of their helping behaviors.
AB  - This paper explores the ways in which primary-care physicians in Israel perceive
      and help poor patients. Our findings are based on a qualitative study that
      utilized a focus group and in-depth interviews with 16 primary-care physicians
      who qualified both in Israel and in the former Soviet Union, and who work in
      community clinics one Health Maintenance Organization serving poor populations of
      diverse cultural, ethnic and socioeconomic backgrounds (immigrants from the
      former Soviet Union and from Ethiopia, Bedouin, ultra-orthodox Jews, the chronic
      poor, and the 'new' poor). It was found that the physicians presume causality
      between poverty and health, identify and distinguish between different types of
      poverty, and make associations based on the type of poverty and type of patient
      problem. Their thinking on poverty is patient-oriented rather than socially
      oriented. An analysis of these findings resulted in a conceptualization of five
      types of physician helping behavior: emotional and personal instrumental,
      reinforcing socially desirable behavior, preferential help and bending the rules,
      rights realization and working the system, and minimal community involvement. The
      components of this conceptual model depict and chart issues affecting the helping
      behavior of the primary-care physician, i.e., type of poverty, type of problem,
      administrative context and, particularly, physician attributes, such as gender
      and country where notable. Our findings reveal little social consciousness on the
      part of the physicians, and we conclude with remarks on the potential for change
      in this area.

PMID- 17234318
TI  - Aripiprazole augmentation in treatment-resistant bipolar depression: early
      response and development of akathisia.
AB  - There is growing evidence that atypical antipsychotics may be effective in the
      treatment of acute bipolar depression. Results from randomized, placebo
      controlled trials support the use of quetiapine monotherapy and a combination of
      olanzapine-fluoxetine in the depressed phase of bipolar disorder, while only
      limited data exists regarding the use of aripiprazole in this population. To
      assess the potential effectiveness of aripiprazole in treating acute bipolar
      depression, a chart review was conducted on 12 patients with treatment-resistant
      bipolar disorder (I, II, and not otherwise specified [NOS]) who received
      aripiprazole augmentation for the relief of an acute major depressive episode.
      After 8 weeks of treatment, 4 of 12 (33%) patients demonstrated a response,
      defined as a 50% reduction in the Montgomery-Asberg Depression Rating Scale
      (MADRS) score. In addition, 5 of 12 (42%) patients newly developed akathisia.
      This report, though limited by its small sample size and naturalistic design,
      suggests that the usefulness of aripiprazole in the treatment of bipolar
      depression may be limited by akathisia.

PMID- 17234319
TI  - Behavioral and biochemical evaluation of sub-lethal inhalation exposure to VX in
      rats.
AB  - We evaluated the effects of low-level inhalation exposures (whole body, 60min
      duration) to the chemical warfare nerve agent VX (0.016, 0.15, 0.30 or
      0.45mg/m(3)) in rats. The range of concentrations was approximately equivalent to
      0.02-0.62 times 1.0 LC50. Biochemical effects were assessed by evaluating blood
      acetylcholinesterase (AChE) activity and by a regeneration assay that quantified
      the amount of VX (as the G analog) present in blood. Behavioral effects were
      assessed using a variable-interval 56-s schedule of reinforcement (VI56), in
      which rats were trained to press a lever to receive a food reward. VI56 training
      was established before exposure and evaluations continued after exposure.
      Additionally, after exposure, acquisition and maintenance of an eight-arm radial
      maze (RAM) task was evaluated in which rats learned to locate the four arms of
      the maze that presented a single food pellet reward. Behavioral assessments were
      conducted over approximately 3 months following exposure. Transient miosis was
      observed following exposure to all concentrations of VX and exposures to the
      0.45mg/m(3) concentration also produced mild and temporary signs of toxicity
      (i.e., slight tremor and ataxia) in some subjects. All concentrations of VX also
      inhibited circulating AChE and the highest concentration inhibited AChE activity
      to less than 10% of pre-exposure values. Regenerated VX-G was found in red blood
      cell (RBC) and plasma blood fractions. In this respect, more VX-G was seen in
      plasma than RBC. Only small disruptions were observed on the VI56 or RAM
      following some VX exposures. In general, however, behavioral effects were minor
      and not clearly systematic. Taken together these results demonstrate that largely
      asymptomatic exposures to VX vapors in rats can produce substantial biochemical
      effects while having only minor performance effects on a previously learned
      behavioral task and on the acquisition of a new behavioral task.

PMID- 17234321
TI  - Ultra long cardiopulmonary resuscitation with intact cerebral performance for an
      asystolic patient with acute myocarditis.
AB  - Cardiopulmonary resuscitation (CPR) for 10-30 min without return of spontaneous
      circulation is considered to have a grave prognosis. We report a 27-year-old
      woman who experienced in-hospital, witnessed cardiac arrest and underwent
      prolonged CPR with manual chest compressions for 280 min. Adequate chest
      compression was monitored with femoral arterial pressure monitoring. During this
      time, she was alert and responsive. She was then supported with extracorporeal
      membrane oxygenation (ECMO) for 9 days without her heart beating. After combined
      heart and kidney transplantation, she recovered well with intact cerebral
      performance. This successful case report supports the endeavours for relentless
      CPR efforts.

PMID- 17234320
TI  - Differential effects of dihydropyridine calcium antagonists on doxorubicin
      induced nephrotoxicity in rats.
AB  - The aim of this study was to compare the roles of dihydropyridine calcium
      antagonists nifedipine, nitrendipine, amlodipine on doxorubicin (DXR)-induced
      nephrotoxicity in rats using biochemical, histopathological and
      immunohistochemical approaches. Male Sprague-Dawley rats were randomly divided
      into five experimental groups: control; DXR; DXR+nifedipine (15 mg/kg);
      DXR+nitrendipine (10 mg/kg); DXR+amlodipine (5 mg/kg). Results showed that
      treatment with DXR alone caused significant changes in the levels of urinary
      protein, serum creatinine (SCr), and blood urea nitrogen (BUN). Co-administration
      with amlodipine effectively reversed the effect of DXR on these parameters. In
      contrast, nifedipine and nitrendipine either had no effect or worsened DXR
      induced changes in the levels of urinary protein, SCr and BUN. Furthermore, DXR
      treatment caused significant increases in the levels of malondialdehyde (MDA),
      nitric oxide (NO), nitric oxide synthase (NOS) and significant decreases in the
      levels of reduced glutathione (GSH), glutathione-S-transferase (GST), and
      superoxide dismutase (SOD). These effects were significantly reduced by co
      administration with amlodipine but not affected by nifedipine and worsened by
      nitrendipine. In addition to the biochemical changes, histopathological studies
      showed that DXR caused significant structural damages in the kidneys. Glomerular
      cell apoptosis, a decrease in Bcl-2 expression and an increase in Bax expression
      were observed in all rats treated with DXR. Co-administration with amlodipine
      effectively reversed the effect of DXR while nifedipine and nitrendipine had no
      effect. In conclusion, this study clearly indicated that amlodipine protected
      against DXR-induced nephrotoxicity while nifedipine and nitrendipine had no
      effect.

PMID- 17234322
TI  - Regulation of intrinsic neuronal properties for axon growth and regeneration.
AB  - Regulation of neuritic growth is crucial for neural development, adaptation and
      repair. The intrinsic growth potential of nerve cells is determined by the
      activity of specific molecular sets, which sense environmental signals and
      sustain structural extension of neurites. The expression and function of these
      molecules are dynamically regulated by multiple mechanisms, which adjust the
      actual growth properties of each neuron population at different ontogenetic
      stages or in specific conditions. The neuronal potential for axon elongation and
      regeneration are restricted at the end of development by the concurrent action of
      several factors associated with the final maturation of neurons and of the
      surrounding tissue. In the adult, neuronal growth properties can be significantly
      modulated by injury, but they are also continuously tuned in everyday life to
      sustain physiological plasticity. Strict regulation of structural remodelling and
      neuritic elongation is thought to be required to maintain specific patterns of
      connectivity in the highly complex mammalian CNS. Accordingly, procedures that
      neutralize such mechanisms effectively boost axon growth in both intact and
      injured nervous system. Even in these conditions, however, aberrant connections
      are only formed in the presence of unusual external stimuli or experience.
      Therefore, growth regulatory mechanisms play an essentially permissive role by
      setting the responsiveness of neural circuits to environmental stimuli. The
      latter exert an instructive action and determine the actual shape of newly formed
      connections. In the light of this notion, efficient therapeutic interventions in
      the injured CNS should combine targeted manipulations of growth control
      mechanisms with task-specific training and rehabilitation paradigms.

PMID- 17234323
TI  - Stability of proteins in the presence of carbohydrates; experiments and modeling
      using scaled particle theory.
AB  - The effects of sucrose and fructose on the free energy of unfolding, DeltaG(N-
      >D), and on the change in hydrodynamic radius, R(H), upon unfolding were measured
      for RNase A and alpha-lactalbumin. Recently we analyzed the results for RNase A
      and showed that the effects of the carbohydrates on the protein's thermal
      stability can be accurately accounted for by scaled particle theory (SPT), and
      are thus largely entropic in nature. In this paper we extend this analysis to
      alpha-lactalbumin and demonstrate the generality of this finding. We also
      investigate the relationship between SPT and the thermodynamic formalism of
      preferential interactions. The preferential binding parameters calculated using
      SPT are in excellent agreement with experimentally measured values available in
      the literature. This agreement is expected to hold as long as enthalpic
      interactions between the cosolute and the protein are not important, as appears
      to be the case here. Finally we use the experimental data and SPT to calculate
      the change in the number of sugar molecules excluded from the protein surface
      during unfolding from knowledge of the preferential binding parameter for the
      native and denatured state of the protein.

PMID- 17234324
TI  - Assessing the impact of urbanization on regional net primary productivity in
      Jiangyin County, China.
AB  - Urbanization is one of the most important aspects of global change. The process
      of urbanization has a significant impact on the terrestrial ecosystem carbon
      cycle. The Yangtze Delta region has one of the highest rates of urbanization in
      China. In this study, carried out in Jiangyin County as a representative region
      within the Yangtze Delta, land use and land cover changes were estimated using
      Landsat TM and ETM+ imagery. With these satellite data and the BEPS process model
      (Boreal Ecosystem Productivity Simulator), the impacts of urbanization on
      regional net primary productivity (NPP) and annual net primary production were
      assessed for 1991 and 2002. Landsat-based land cover maps in 1991 and 2002 showed
      that urban development encroached large areas of cropland and forest. Expansion
      of residential areas and reduction of vegetated areas were the major forms of
      land transformation in Jiangyin County during this period. Mean NPP of the total
      area decreased from 818 to 699 gCm(-2)yr(-1) during the period of 1991 to 2002.
      NPP of cropland was only reduced by 2.7% while forest NPP was reduced by 9.3%.
      Regional annual primary production decreased from 808 GgC in 1991 to 691 GgC in
      2002, a reduction of 14.5%. Land cover changes reduced regional NPP directly, and
      the increasing intensity and frequency of human-induced disturbance in the
      urbanized areas could be the main reason for the decrease in forest NPP.

PMID- 17234325
TI  - Impacts of recreation and tourism on plant biodiversity and vegetation in
      protected areas in Australia.
AB  - This paper reviews recent research into the impact of recreation and tourism in
      protected areas on plant biodiversity and vegetation communities in Australia.
      Despite the international significance of the Australian flora and increasing
      visitation to protected areas there has been limited research on recreational and
      tourism impacts in Australia. As overseas, there are obvious direct impacts of
      recreation and tourism such as clearing of vegetation for infrastructure or
      damage from trampling, horse riding, mountain biking and off road vehicles. As
      well, there are less obvious but potentially more severe indirect impacts. This
      includes self-propagating impacts associated with the spread of some weeds from
      trails and roads. It also includes the severe impact on native vegetation,
      including many rare and threatened plants, from spread of the root rot fungus
      Phytopthora cinnamomi. This review highlights the need for more recreational
      ecology research in Australia.

PMID- 17234326
TI  - Multiple regression models for the lower heating value of municipal solid waste
      in Taiwan.
AB  - A multiple regression analysis was used to develop two predictive models of lower
      heating value (LHV) for municipal solid waste (MSW), using 180 samples gathered
      from cities and counties in Taiwan during 2001-2002. These models are referred to
      as the original proposed model (OPM) and the simplified model (SM). The
      coefficients of multiple determinations for the OPM and SM were 0.983 and 0.975,
      respectively. To verify the feasibility of the models, a demonstration program
      based on sampling of MSW in Kaohsiung City was conducted. As a result, the OPM
      showed superior precision in terms of relative percentage deviation (RPD) and
      mean absolute percentage error (MAPE), when compared to the conventional models
      based on the proximate analysis, physical composition and ultimate analysis. The
      SM was derived by neglecting the three minor physical components used in the OPM.
      The resulting SM was less precise when compared to the OPM, but it was still
      acceptable, with a precision level better than the conventional models. It was
      concluded that the predictability of empirical models could be improved
      significantly through selection of the appropriate physical components and
      multiple regression analysis.

PMID- 17234327
TI  - Net primary productivity of China's terrestrial ecosystems from a process model
      driven by remote sensing.
AB  - The terrestrial carbon cycle is one of the foci in global climate change
      research. Simulating net primary productivity (NPP) of terrestrial ecosystems is
      important for carbon cycle research. In this study, China's terrestrial NPP was
      simulated using the Boreal Ecosystem Productivity Simulator (BEPS), a carbon
      water coupled process model based on remote sensing inputs. For these purposes, a
      national-wide database (including leaf area index, land cover, meteorology,
      vegetation and soil) at a 1 km resolution and a validation database were
      established. Using these databases and BEPS, daily maps of NPP for the entire
      China's landmass in 2001 were produced, and gross primary productivity (GPP) and
      autotrophic respiration (RA) were estimated. Using the simulated results, we
      explore temporal-spatial patterns of China's terrestrial NPP and the mechanisms
      of its responses to various environmental factors. The total NPP and mean NPP of
      China's landmass were 2.235 GtC and 235.2 gCm(-2)yr(-1), respectively; the total
      GPP and mean GPP were 4.418 GtC and 465 gCm(-2)yr(-1); and the total RA and mean
      RA were 2.227 GtC and 234 gCm(-2)yr(-1), respectively. On average, NPP was 50.6%
      of GPP. In addition, statistical analysis of NPP of different land cover types
      was conducted, and spatiotemporal patterns of NPP were investigated. The response
      of NPP to changes in some key factors such as LAI, precipitation, temperature,
      solar radiation, VPD and AWC are evaluated and discussed.

PMID- 17234328
TI  - Creating affordable Internet map server applications for regional scale
      applications.
AB  - This paper presents an overview and process for developing an Internet Map Server
      (IMS) application for a local volunteer watershed group using an Internal
      Internet Map Server (IIMS) strategy. The paper illustrates that modern GIS
      architectures utilizing an internal Internet map server coupled with a spatial
      SQL command language allow for rapid development of IMS applications. The
      implication of this approach means that powerful IMS applications can be rapidly
      and affordably developed for volunteer organizations that lack significant funds
      or a full time information technology staff.

PMID- 17234329
TI  - Environmental protection, the economy, and jobs: national and regional analyses.
AB  - The relationship between environmental protection (EP), the economy, and jobs has
      been an issue of harsh contention for decades. Does EP harm the economy and
      destroy jobs or facilitate economic growth and create jobs? We address this issue
      by summarizing the results of the Jobs and the Environment Initiative, research
      funded by nonprofit foundations to quantify the relationship between EP, the
      economy, and jobs. We estimate the size of the US environmental industry and the
      numbers of environment-related jobs at the national level and in the states of
      Florida, Michigan, Minnesota, North Carolina, Ohio, and Wisconsin. This is the
      first time that such comprehensive, detailed estimates have been developed. Our
      major finding is that, contrary to conventional wisdom, EP, economic growth, and
      jobs creation are complementary and compatible: investments in EP create jobs and
      displace jobs, but the net effect on employment is positive. Second, environment
      protection has grown rapidly to become a major sales-generating, job-creating
      industry--$300 billion/year and 5 million jobs in 2003. Third, most of the 5
      million jobs created are standard jobs for accountants, engineers, computer
      analysts, clerks, factory workers, etc., and the classic environmental job
      (environmental engineer, ecologist, etc.) constitutes only a small portion of the
      jobs created. Most of the persons employed in the jobs created may not even
      realize that they owe their livelihood to protecting the environment. Fourth, at
      the state level, the relationship between environmental policies and economic/job
      growth is positive, not negative. States can have strong economies and
      simultaneously protect the environment. Finally, environmental jobs are
      concentrated in manufacturing and professional, information, scientific, and
      technical services, and are thus disproportionately the types of jobs all states
      seek to attract.

PMID- 17234330
TI  - Editorial comment on: Correction of congenital penile curvature using modified
      tunical plication with absorbable sutures: the long-term outcome and patient
      satisfaction.

PMID- 17234331
TI  - Prospective clinical trial comparing Obtape and DUPS to TVT: one-year safety and
      efficacy results.
AB  - OBJECTIVES: Obtape and DUPS are modifications of the original TVT procedure. To
      test these new products in terms of safety and efficacy, we designed a
      prospective clinical trial with a follow-up of at least 1 yr. METHODS: We
      randomized 190 consecutive females with SUI for this study. They were evaluated
      by history, ICIQ-SF, physical examination, cystoscopy, UDS, and the 1-h pad test.
      Patients were reevaluated at 1, 6, and 12 mo. The ICIQ-SF and pad test were
      repeated at 1-yr follow-up. RESULTS: There were 78, 32, and 80 patients in the
      Obtape, DUPS, TVT arms, respectively. An interim analysis after 32 patients in
      each arm indicated postoperative retention rates of 3 (9.4%), 6 (18.8%), and 4
      (12.5%) patients in Obtape, DUPS, and TVT groups, respectively. Because of higher
      retention rate and suprapubic discomfort, DUPS was discontinued. At the end of
      the study, complete retention rates were 6 (7.8%), 6 (18.8%), and 6 (7.5%) in
      Obtape, DUPS, and TVT, respectively. TVT was the only procedure with bladder
      perforations at a rate of 14%. However, Obtape and DUPS were associated with more
      postoperative complications including complete retention, urethrolysis, hematoma,
      mesh erosion, UTI, and wound infection (13%, 28%, and 8%; p< or =0.025). At 1 yr,
      83%, 94%, and 86% of patients in the Obtape, DUPS, and TVT groups were
      objectively cured (p>0.05). CONCLUSIONS: TVT was the only procedure associated
      with bladder perforation, but there were more postoperative complications with
      Obtape and DUPS. No statistically significant differences in cure rates were
      observed at 1-yr follow-up. Longer follow-up is needed to confirm these results.

PMID- 17234332
TI  - Editorial comment on: Prospective clinical trial comparing Obtape and DUPS to
      TVT: one-year safety and efficacy results.

PMID- 17234333
TI  - Correction of congenital penile curvature using modified tunical plication with
      absorbable sutures: the long-term outcome and patient satisfaction.
AB  - OBJECTIVES: Although plication of the tunica albuginea with nonabsorbable sutures
      is an effective method in correcting congenital penile curvature (CPC), suture
      related complications may happen. We investigated the long-term outcome and
      patient satisfaction of a modified tunical plication technique using absorbable
      sutures. MATERIALS AND METHODS: From January 1999 to July 2005, 114 consecutive
      patients with CPC treated with a modified tunical plication technique by a single
      surgeon were retrospectively reviewed. With the modified corporeal plication
      technique, two, interrupted, U-shaped sutures with 2-zero polyglactin were
      applied to create bumps on the tunica albuginea. The long-term outcome and
      patient satisfaction were assessed by a post hoc questionnaire interview.
      RESULTS: Among the 114 patients, complete straightness of the penis was achieved
      in 65 (57%) patients, and 33 (29%) patients reported a 15-degree or less residual
      or recurrent curvature at 6 mo postoperatively. Although 32 (28%) patients
      experienced suture failure (median time: 38.5 d), only half of them had a
      residual or recurrent curvature greater than 15 degrees. Younger patients (<24
      yr) had a higher chance of suture failure than elder patients (p=0.03). Among the
      103 patients completing the questionnaire, no palpable suture knots, suture
      granuloma, erectile discomfort, or erectile dysfunction was reported (median
      follow-up time: 41.5 mo). Eighty-three (81.5%) patients were either very or
      moderately satisfied with the surgical outcome. CONCLUSIONS: The modified
      technique using double, interrupted, U-shaped sutures and absorbable suture
      material is a simple and effective method for treating CPC. Suture-related
      complications rarely happen. The long-term outcome is satisfactory, and most
      patients are pleased with the procedure.

PMID- 17234334
TI  - FSH stimulates ovarian cancer cell growth by action on growth factor variant
      receptor.
AB  - A number of FSH receptor (FSH-R) isoforms with distinct structural motifs and
      signaling paradigms have been described, including a single transmembrane domain
      variant that functions as a growth factor type receptor (FSH-R3). This study
      tested the hypothesis that FSH can stimulate ovarian cancer cell proliferation by
      acting on FSH-R3, using the tumorigenic mouse ovarian surface epithelial cell
      (MOSEC) line ID8. FSH enhanced ID8 proliferation in a concentration-dependent
      fashion. Moreover, FSH-treatment of ID8 elicited intracellular events consistent
      with activation of FSH-R3 and distinct from those associated with activation of
      the canonical G-protein coupled FSH-R isoform (FSH-R1). Specifically, the FSH-R3
      signaling pathway included cAMP-independent activation of ERK downstream of an
      SNX-482 sensitive component likely to be the Cav2.3 calcium channel. Northern
      analysis using probes specific for exons 7 and 11 of FSH-R identified
      consistently only one 1.9kb transcript. Immunoblot analysis confirmed expression
      of FSH-R3 but not FSHR-1 in ID8. Together, these data suggest that FSH-R3
      signaling promotes proliferation of ovarian cancer cells.

PMID- 17234335
TI  - SDR-type human hydroxysteroid dehydrogenases involved in steroid hormone
      activation.
AB  - Hydroxysteroid dehydrogenases catalyze the NAD(P)(H)-dependent oxidoreduction of
      hydroxyl and oxo-functions at distinct positions of steroid hormones. This
      reversible reaction constitutes an important pre-receptor control mechanism for
      nuclear receptor ligands of the androgen, estrogen and glucocorticoid classes,
      since the conversion "switches" between receptor ligands and their inactive
      metabolites. The major reversible activities found in mammals acting on steroid
      hormones comprise 3alpha-, 11beta- and 17beta-hydroxysteroid dehydrogenases, and
      for each group several distinct isozymes have been described. The enzymes differ
      in their expression pattern, nucleotide cofactor preference, steroid substrate
      specificity and subcellular localization, and thus constitute a complex system
      ensuring cell-specific adaptation and regulation of steroid hormone levels.
      Several isoforms constitute promising drug targets, of particular importance in
      cancer, metabolic diseases, neurodegeneration and immunity.

PMID- 17234336
TI  - Fabry disease mimicking multiple sclerosis.
AB  - Fabry disease is an X-linked recessive lysosomal storage disorder resulting from
      the deficiency of alpha-galactosidase. This disease causes endothelial
      vasculopathy and affects multiple organ systems. Hemizygous male patients
      represent the classical renal, cardiac and neurological symptoms of disease.
      Heterozygous female carriers are frequently asymptomatic, but cerebrovascular
      events in females are as frequent as in males. Even if rarely seen, neurological
      damage is an important cause of morbidity. Severe neurological signs that are due
      to multifocal small vessel occlusions may be present without major thrombosis. In
      this report, we present a 33-year-old female patient with recurrent neurological
      deficits secondary to multifocal small vessel involvements. The case had
      previously been misdiagnosed as multiple sclerosis. Cerebral MRI revealed
      hyperintense lesions located in bilateral thalamus, supratentorial areas, and
      left cerebellum. Laboratory and radiological investigations were performed for
      differential diagnosis, but the etiology could not be identified. During follow
      up period, skin lesions and proteinuria were detected. The dermatological,
      neurological, laboratory, and radiological findings were all suggestive of Fabry
      disease and the diagnosis was confirmed by subsequent enzyme assays. Fabry
      disease should be considered in young patients with unexplained stroke-like
      episodes, especially in those who have infarction in the vertebrobasilar arterial
      system, angiokeratomas, and proteinuria.

PMID- 17234337
TI  - Arecoline inhibits the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome
      P450 1A1 activation in human hepatoma cells.
AB  - In the present study, we investigated the effect of arecoline, a major areca nut
      alkaloid, on the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of
      cytochrome P4501A1 (CYP1A1) in a human hepatoma cell line Huh-7. We treated Huh-7
      cells with 10nM TCDD in the presence of different concentrations of arecoline (50
      300 microM). Our results indicated that arecoline attenuated the TCDD-induced
      CYP1A1 enzyme activation with an inhibitory effect on cell proliferation. By
      using real-time RT-PCR, we demonstrated that arecoline inhibited the TCDD-induced
      activations of CYP1A1 and AhR repressor (AhRR) mRNA expression in a similar
      pattern. Our results revealed that arecoline inhibited AhR mRNA expression with
      no direct effect on CYP1A1 enzyme activity. Therefore, in our present study, the
      observed inhibitory effect of arecoline on CYP1A1 activation was not due to the
      up-regulation of AhRR or direct inhibitory effect on CYP1A1. Taken together, here
      we have demonstrated that arecoline attenuates the TCDD-induced CYP1A1 activation
      mainly via down-regulation of AhR expression in human hepatoma cells, suggesting
      the possible involvement of arecoline in the AhR-mediated metabolism of
      environmental toxicants in liver.

PMID- 17234338
TI  - Evidence for interplay between thyrotropin-releasing hormone (TRH) and its
      structural analogue pGlu-Glu-Pro-NH2 ([Glu2]TRH) in the brain: an in vivo
      microdialysis study.
AB  - Local perfusion of pGlu-Glu-Pro-NH2, an endogenous peptide structurally related
      to thyrotropine-releasing hormone (TRH), via in vivo microdialysis into the rat
      hippocampus did not change the basal level of extracellular acetylcholine.
      However, co-perfusion of pGlu-Glu-Pro-NH2 with TRH in equimolar concentrations
      yielded a significant attenuation of TRH-induced acetylcholine release. The
      results have supported the study's hypothesis that pGlu-Glu-Pro-NH2 opposes the
      cholinergic effect of TRH in the mammalian central nervous system. The enantiomer
      pGlu-d-Glu-Pro-NH2 affected neither basal extracellular nor TRH-induced increase
      of acetylcholine levels.

PMID- 17234340
TI  - Only high concentrations of ethanol affect GABAA receptors of rat cerebellum
      granule cells in culture.
AB  - In the experiments described in the present report, we evaluated the effects of
      ethanol on the activity of GABAA receptors of cerebellar granule cells in
      culture. Only very high ethanol concentrations (100-300 mM) showed a clear and
      significant stimulatory effect on the activity of such receptors. This result was
      unexpected. In fact, previous reports from other groups would have suggested high
      ethanol sensitivity of at least one population of GABAA receptors expressed by
      granule cells.

PMID- 17234339
TI  - Suppression of p53-activated gene, PAG608, attenuates methamphetamine-induced
      neurotoxicity.
AB  - The p53-activated gene 608 (PAG608) is a proapoptotic gene activated and
      regulated by p53 expression in oxidative stress-induced apoptosis of neuronal
      cells. In this study, we determined the role of PAG608 in methamphetamine-induced
      neurotoxicity. Treatment of mouse dopaminergic CATH.a cells with 2 mM
      methamphetamine increased PAG608 expression at 3h followed by increase in
      phosphorylated p53 expression. Transient transfection of PAG608 antisense cDNA or
      RNA interference using PAG608 small interfering RNA significantly attenuated the
      dose-dependent decrease in cell viability of CATH.a cells by methamphetamine (1-4
      mM) exposure. In monoaminergic neuronal B65 cells, which contain serotonin rather
      than dopamine, methamphetamine-induced cell death was also significantly but
      partially protected by transient transfection of PAG608 antisense cDNA.
      Furthermore, cell death of PC12 cells produced by methamphetamine (1-5 mM) was
      almost completely prevented by stable expression of PAG608 antisense cDNA,
      compared with significant reduction of cell viability in control PC12 cells. Our
      results showed that suppression of PAG608 using transient and stable transfection
      with PAG608 antisense cDNA or small interfering RNA attenuates methamphetamine
      induced death of various monoaminergic neuronal cells, suggesting that
      methamphetamine neurotoxicity in monoaminergic cells is related, at least in
      part, to induction of PAG608 expression.

PMID- 17234341
TI  - Dynorphin displaces binding at the glycine site of the NMDA receptor in the rat
      striatum.
AB  - Binding of dynorphin A (1-17 and 2-17) to NMDA receptors in the rat striatum was
      studied by displacing radioactive ligands for the receptor's polyamine ([3H]
      Ifenprodil), glutamate ([3H]-CGP-39653), dizocilpine ([3H]-MK-801) and glycine
      ([3H]-MDL105,519) sites with the neuropeptide. Dynorphin A selectively displaced
      [3H]-MDL105,519 and none of the other ligands. Opioid antagonists did not affect
      displacement. Thus, in the striatum dynorphin may regulate NMDA receptor function
      via the glycineB site through non-opioid mechanisms. This may contribute to the
      long-term changes in behavioral responsiveness seen after dopamine depletion and
      treatment with dopaminomimetics which are associated with substantial changes in
      striatal dynorphin metabolism.

PMID- 17234342
TI  - Differential involvement of cyclase- versus non-cyclase-coupled D1-like dopamine
      receptors in orofacial movement topography in mice: studies with SKF 83822.
AB  - Though orofacial movements are fundamental motor patterns that are known to be
      regulated critically by D1-like dopamine receptors, these processes remain poorly
      understood. This uncertainty is heightened by evidence for putative D1-like
      receptors that are linked not only to adenylyl cyclase (AC) but also to
      phospholipase C (PLC). Using a new method, we have characterised four
      topographies of orofacial movement in the mouse using the novel D1-like agonist
      SKF 83822, which stimulates AC but not PLC. These were compared with responses to
      SKF 83959, which stimulates PLC but not AC. Also, effects were characterised
      using the D1-like antagonist SCH 23390 and the D2-like antagonist YM 09151-2. SKF
      83822 induced vertical jaw movements with incisor chattering but inhibited
      horizontal jaw movements; there was little effect on tongue protrusions. Vertical
      jaw movements induced by SKF 83822 were inhibited by SCH 23390 but uninfluenced
      by YM 09151-2, while YM 09151-2 released horizontal jaw movements; thus, D1-like
      agonist-induced, AC-mediated vertical jaw movements constitute a 'pure' D1-like
      dependent process that does not involve D1-like:D2-like interactions, while
      horizontal jaw movements involve oppositional interactions. Orofacial movements
      in mice appear to consist of at least four phenomenologically dissociable
      topographies that are mechanistically distinct. They are regulated differentially
      by AC- and/or PLC-dependent processes and these processes involve distinct D1
      like:D2-like interactions.

PMID- 17234343
TI  - Cerebral oxidative metabolism in rats with high and low exploratory activity.
AB  - To reveal brain regions most significantly related to individual differences in
      exploratory behaviour, oxidative metabolism was measured by cytochrome c oxidase
      histochemistry in 2 months old Wistar rats with persistently high (HE) or low
      (LE) exploratory activity in a novel environment. LE-rats had significantly
      higher levels of oxidative metabolism in dorsal raphe and inferior colliculi. In
      contrast, HE-rats had higher metabolic activity in entorhinal cortex. In
      conclusion, rats with different exploratory styles differ in underlying cerebral
      activity as measured via oxidative metabolism in regions implicated in defensive
      behaviours and cognitive processing of sensory stimuli.

PMID- 17234344
TI  - Serum neurotrophin-3 is increased during manic and depressive episodes in bipolar
      disorder.
AB  - Accumulating evidence suggest that neural changes and cognitive impairment may
      accompany the course of bipolar disorder. Such detrimental effects of cumulative
      mood episodes may be related to changes in neurotrophins that take place during
      mood episodes but not during euthymic phases. The present study investigated
      serum neurotrophin-3 (NT-3) levels in patients with bipolar disorder during
      manic, depressed, and euthymic states, using an enzyme-linked immunosorbent assay
      (sandwich-ELISA). Serum NT-3 levels were increased in manic (p<0.001) and
      depressed (p<0.001) BD patients, as compared with euthymic patients and normal
      controls. These findings suggest that the NT-3 signaling system may play a role
      in the pathophysiology of BD.

PMID- 17234345
TI  - Thioperamide delays vestibular compensation in goldfish.
AB  - Unilateral lesion of the vestibular system induces posturo-locomotor deficits
      that are compensated for with time. Drug therapy is currently used to improve the
      recovery process and to facilitate vestibular compensation. We investigated the
      effects of thioperamide on functional recovery after unilateral labyrinthectomy
      in Carassius auratus. Approximately 24h after surgery, the animals were injected
      intraperitoneally with thioperamide (15 mg/kg) and saline (1.5 ml/kg). The
      injections were repeated daily for a total of 15 consecutive days. The substances
      were administered in a volume of 1.5 ml/kg body weight. Another group, which
      served as a non-lesion control, did not receive unilateral labyrinthectomy or
      system injections. Animals treated with saline presented a compensatory decrease
      in body tilt on the 7th day, while the animals treated with thioperamide
      presented a decrease in body tilt from the 13th day, suggesting a delay in the
      functional recovery process. These results suggest that an increase in cerebral
      histamine levels impairs vestibular compensation in goldfish.

PMID- 17234346
TI  - Lovastatin protects human neurons against Abeta-induced toxicity and causes
      activation of beta-catenin-TCF/LEF signaling.
AB  - Alzheimer's disease (AD) is characterized by cognitive decline due to excess
      amyloid beta peptide (Abeta), neurofibrillary tangles, and neuronal loss. Abeta
      promotes neuronal apoptosis in AD by activating glycogen synthase kinase-3beta
      (GSK-3beta), leading to degradation of beta-catenin and inactivation of Wnt
      signaling. beta-Catenin interacts with the T-cell factor (TCF)/Lymphoid enhancer
      factor (LEF)-nuclear complex to mediate Wnt signaling and cell survival. Statins
      are associated with decreased prevalence of AD. Lovastatin has been shown to
      decrease the production of Abeta and to promote neuronal survival. The mechanisms
      of how statins promote neuronal survival are unclear. We propose that the
      neuroprotective effect of lovastatin may be due to inactivation of GSK-3beta
      activity, resulting in induction of Wnt signaling. Here, we report that
      lovastatin prevented Abeta-induced apoptosis in human SK-NSH cells. This was
      accompanied by reduction in active GSK-3beta, and increased nuclear translocation
      of beta-catenin, TCF-3, and LEF-1. Lovastatin treatment induced an increase in
      TCF/LEF-chloramphenicol acetyl transferase (CAT) gene reporter activity. More
      importantly, beta-catenin and TCF were required for the neuroprotective function
      of lovastatin. Our results suggest that lovastatin protects neuronal cells from
      Abeta-induced apoptosis and causes reduction in GSK-3beta activity, resulting in
      activation of Wnt signaling.

PMID- 17234347
TI  - Towards automated diffraction tomography: part I--data acquisition.
AB  - The ultimate aim of electron diffraction data collection for structure analysis
      is to sample the reciprocal space as accurately as possible to obtain a high
      quality data set for crystal structure determination. Besides a more precise
      lattice parameter determination, fine sampling is expected to deliver superior
      data on reflection intensities, which is crucial for subsequent structure
      analysis. Traditionally, three-dimensional (3D) diffraction data are collected by
      manually tilting a crystal around a selected crystallographic axis and recording
      a set of diffraction patterns (a tilt series) at various crystallographic zones.
      In a second step, diffraction data from these zones are combined into a 3D data
      set and analyzed to yield the desired structure information. Data collection can
      also be performed automatically, with the recent advances in tomography
      acquisition providing a suitable basis. An experimental software module has been
      developed for the Tecnai microscope for such an automated diffraction pattern
      collection while tilting around the goniometer axis. The module combines STEM
      imaging with diffraction pattern acquisition in nanodiffraction mode. It allows
      automated recording of diffraction tilt series from nanoparticles with a size
      down to 5nm.

PMID- 17234348
TI  - Structure determination of the hexagonal quasicrystal approximant micro'
      (Al,Si)4Cr by the strong reflections approach.
AB  - A number of different crystalline phases have been found in Al-rich Al-Cr-Si
      alloys by transmission electron microscopy (TEM). Among these, the new hexagonal
      phase micro'-(Al,Si)(4)Cr (a=2.01 and c=1.24 nm) often found coexisting with the
      hexagonal micro-(Al,Si)(4)Cr (a=1.998 and c=2.4673 nm, isostructural with micro
      Al(4)Mn) and also with the hexagonal lambda-(Al,Si)(4)Cr (a=2.839 and c=1.239 nm,
      isostructural with lambda-Al(4)Mn). It is evident from their electron diffraction
      patterns that the structures of these three phases are related. The strong
      reflections in all three are distributed in a similar way. They all exhibit a
      pseudo-icosahedral symmetry. The structure factor amplitudes and phases for the
      strong reflections of the micro' phase could therefore be adopted from those of
      the lambda phase, according to the strong reflections approach. A structure model
      of the micro' phase is thus deduced from the known lambda-Al(4)Mn. micro'
      consists of chains of 3+3 or 4+2 interpenetrated icosahedra along the 100
      directions. Similar to the lambda phase, there are two flat layers (F) and four
      puckered layers (P) in each unit cell of micro', stacked along the c-axis in a
      sequence of PFP(PFP)' where the (PFP)' block is related to the PFP block by a
      6(3) screw.

PMID- 17234349
TI  - The implications of a new Code of Practice on the storage of human skin for a
      regional plastic surgery unit.

PMID- 17234350
TI  - Adenosine in burn blister fluid.
AB  - BACKGROUND: Burn wound blister fluid is known to sustain suppressive effects on
      various components of the immune system. Damaged tissues cause an increase of
      adenosine concentrations. Since adenosine is a potent anti-inflammatory agent we
      hypothesized that burn blister fluid contains high concentrations of this
      nucleoside. METHODS: Burn blister fluid was drawn from eleven patients who
      suffered a second degree burn injury. Adenosine concentrations were determined
      using high performance liquid chromatography (HPLC). RESULTS: Elevated adenosine
      levels were detected in 6 of the 11 patients (54.5%), with an overall mean of
      1.13+/-0.52 mM. CONCLUSIONS: This is the first documented data showing increased
      concentrations of adenosine in burn blister fluid.

PMID- 17234351
TI  - Prevalence of toxin producing strains of Staphylococcus aureus in a pediatric
      burns unit.
AB  - The aims of the study were to determine the sites in a pediatric burns unit that
      were contaminated with Staphylococcus aureus. Samples from the environment in
      bedrooms and the common room were taken monthly for 6 months using blood agar for
      total counts and Baird-Parker agar for S. aureus. The air was sampled using an
      air-sampling device and settle plates. Hard and soft surfaces including bed,
      blanket, sofa, chair, taps, bathtub, soft toys, locker and cupboard in the same
      rooms were sampled using contact plates. Swabs were taken from staff monthly for
      3 months. S. aureus isolates were tested for production of enterotoxins A-D and
      toxic shock syndrome toxin-1 using a reverse passive latex agglutination test.
      The results showed that S. aureus was recovered more frequently using settle
      plates than using the air sampler. All surfaces sampled were contaminated with S.
      aureus and contamination was greatest in frequently occupied rooms. A variety of
      toxin producing isolates were found with enterotoxin C isolates, either alone or
      in combination with TSST-1 (toxic shock syndrome toxin-1) dominant. The staff
      were transiently colonised with S. aureus strains with a different toxin
      production pattern. The results show that airborne transmission may be a route
      for infection by S. aureus and is responsible for contaminating the environment.

PMID- 17234352
TI  - Scientometric identification of elite 'revolutionary science' research
      institutions by analysis of trends in Nobel prizes 1947-2006.
AB  - Most research is 'normal science' using Thomas Kuhn's term: checking, trial-and
      error improvement and incremental extrapolation of already existing paradigms. By
      contrast, 'revolutionary science' changes the fundamental structures of science
      by making new theories, discoveries or technologies. Science Nobel prizes (in
      Physics, Chemistry, Physiology/Medicine and Economics) have the potential to be
      used as a new metric for measuring revolutionary science. Nobel laureates'
      nations and research institutions were measured between 1947 and 2006 in 20 year
      segments. The minimum threshold for inclusion was 3 Nobel prizes. Credit was
      allocated to each laureate's institution and nation of residence at the time of
      award. Over 60 years, the USA has 19 institutions which won three-plus Nobel
      prizes in 20 years, the UK has 4, France has 2 and Sweden and USSR 1 each. Four
      US institutions won 3 or more prizes in all 20 year segments: Harvard, Stanford,
      Berkeley and CalTech. The most successful institution in the past 20 years was
      MIT, with 11 prizes followed by Stanford (9), Columbia and Chicago (7). But the
      Western United States has recently become the world dominant region for
      revolutionary science, generating a new generation of elite public universities:
      University of Colorado at Boulder; University of Washington at Seattle; and the
      University of California institutions of Santa Barbara, Irvine, UCSF, and UCLA;
      also the Fred Hutchinson CRC in Seattle. Since 1986 the USA has 16 institutions
      which have won 3 plus prizes, but elsewhere in the world only the College de
      France has achieved this. In the UK Cambridge University, Cambridge MRC unit,
      Oxford and Imperial College have declined from 17 prizes in 1967-86 to only 3
      since then. Harvard has also declined as a revolutionary science university from
      being the top Nobel-prize-winning institution for 40 years, to currently joint
      sixth position. Although Nobel science prizes are sporadically won by numerous
      nations and institutions, it seems that long term national strength in
      revolutionary science is mainly a result of sustaining and newly-generating multi
      Nobel-winning research centres. At present these elite institutions are found
      almost exclusively in the USA. The USA is apparently the only nation with a
      research system that nurtures revolutionary science on a large scale.

PMID- 17234353
TI  - Which are the best nations and institutions for revolutionary science 1987-2006?
      Analysis using a combined metric of Nobel prizes, Fields medals, Lasker awards
      and Turing awards (NFLT metric).
AB  - I have previously suggested that Nobel prizes can be used as a scientometric
      measurement of 'revolutionary science'; and that for this purpose it would be
      better if more Nobel prizes were awarded, especially in three new subjects of
      mathematics, medicine and computing science which have become major sciences over
      recent decades. In the following analysis of the last 20 years from 1987 to 2006,
      I use three prestigious prizes in mathematics (Fields medal), medicine (Lasker
      award for Clinical Medical Research) and computing science (A.M. Turing award)
      which are plausible surrogates for Nobel prizes. The combined Nobel-Fields-Lasker
      Turing (NFLT) metric is strongly dominated by the USA. However the distribution
      implies that revolutionary science may be somewhat more broadly distributed than
      the pure Nobel metric suggests. The UK and France seem to be significant nations
      in some types of revolutionary science (although the UK has declined
      substantially as a centre of revolutionary science); and Germany, Switzerland,
      Japan, Russia, Denmark and Norway also feature. The top world institutions for
      revolutionary science according to NFLT are MIT, Stanford and Princeton - all in
      the USA - and the USA has 19 institutions with at least three prize-winners.
      Second is France, with three institutions having three or more winners; the UK
      and Norway have one each. The NFLT metric confirms previous observations that
      many public universities in the Western USA have now become a major focus of
      revolutionary science; and that Harvard has declined from its previous status as
      the top world centre of revolutionary science to about seventh-place. This
      analysis confirms the potential value of increasing the number of Nobel prizes as
      a means of identifying and monitoring centres of excellence in revolutionary
      science.

PMID- 17234354
TI  - Implantable central venous access ports for minimally invasive repetitive
      drainage of pleural effusions.
AB  - BACKGROUND: Pleurodesis can often eliminate recurrence of malignant pleural
      effusions and perhaps even pleural effusions from congestive heart failure.
      However, for patients with recurrent pleural effusions resistant to pleurodesis
      or patients unable or unwilling to undergo pleurodesis, thoracentesis is
      currently the only means for removing a pleural effusion. PRESENTATION OF THE
      HYPOTHESIS: Central venous access ports used for cancer chemotherapy could be
      implanted with the lumens placed in the pleural space, allowing on demand
      drainage of pleural effusions by percutaneous access to the port. TESTING THE
      HYPOTHESIS: Initial trials with a swine model of pleural effusions could
      demonstrate proof-of-principle and determine the caliber of catheter lumen
      optimal for pleural effusion drainage. Subsequently, there could be clinical
      trials in humans. SIGNIFICANCE OF THE HYPOTHESIS: This could be a useful part of
      palliative care of patients with cancer and end-stage heart failure and might
      increase heart failure survival by improving hemodynamics and respiratory
      function. This technique would create a non-diuretic modality for treatment of
      congestive heart failure volume overload. Patients could potentially drain
      pleural effusions at home by accessing ports placed in the anterior chest or
      abdomen. The proposed technique might also have application for treatment of
      recurrent ascites.

PMID- 17234355
TI  - Is lipid lowering treatment aiming for very low LDL levels safe in terms of the
      synthesis of steroid hormones?
AB  - Today atherosclerotic diseases are among the most important causes of death in
      the world. Epidemiological, clinical, genetic, experimental and pathological
      studies have clearly shown the role of lipoproteins in atherosclerosis. LDL is
      the major atherogenic lipoprotein and has been defined as the primary target of
      lipid lowering treatment by NCEP. Although the level of LDL, the primary target
      in the treatment of dyslipidemia, has been set as below 100 mg/dl in coronary
      heart diseases (CHD) and CHD risk equivalents, this level has been pulled down to
      below 70 mg/dl for the group defined as very high risk group by the ATP (Adult
      Treatment Panel) guide that has been updated following the new clinical studies.
      As we already know, cholesterol is the precursor of glucocorticoids,
      mineralocorticoids and sex steroids, besides being a structural component of the
      cell membrane. Both adrenal and non-adrenal (ovarian+testicular) all steroid
      hormones are primarily synthesized using the LDL-cholesterol in the circulation.
      In addition to this, there is 'de novo' cholesterol synthesis in both the
      adrenals and gonads controlled by the HMG-CoA reductase enzyme. A third pathway,
      which under normal circumstances has little contribution as compared to the first
      two, is the use of circulatory HDL-cholesterol by the adrenal and gonadal tissues
      for the synthesis of steroids. Our knowledge on extremely lowered LDL levels is
      quite limited. However, since statins both decrease circulatory LDL and inhibit
      de novo cholesterol synthesis, they are likely to affect the synthesis of steroid
      hormones.

PMID- 17234356
TI  - Evaluation of the prognostic value of Okuda, Cancer of the Liver Italian Program,
      and Japan Integrated Staging systems for hepatocellular carcinoma patients
      undergoing radiotherapy.
AB  - PURPOSE: The purpose of this study was to compare the validity of staging
      systems, as well as to identify the staging system with the best prognostic
      value, in hepatocellular carcinoma (HCC) patients treated with radiotherapy.
      METHODS AND MATERIALS: From 1992 to 2003, a total of 305 patients undergoing
      radiotherapy for HCC were evaluated retrospectively. All patients were classified
      before radiation therapy by the following systems: tumor-node-metastasis (TNM),
      Okuda, Cancer of the Liver Italian Program (CLIP), and Japan Integrated Staging
      (JIS) score. Cumulative survival rates were obtained using the Kaplan-Meier
      method, and were statistically compared using the log-rank test. RESULTS: Median
      survival time was 11 months. The 1-, 2-, 3-, 4-, and 5-year survival rates were
      45.1%, 24.5%, 14.7%, 10.3%, and 6.4%, respectively. Significant differences in
      survival were observed between all TNM stages, between CLIP scores 2, 3 and 5, 6,
      as well as between JIS scores 1, 2, and 2, 3. CONCLUSIONS: Among the systems
      studied, the TNM staging approach appeared to be the best predictor of prognosis.
      Staging systems that reflect liver disease status (Okuda stage, CLIP, and JIS
      score) showed limitations in stratifying patients undergoing radiotherapy into
      different prognostic groups.

PMID- 17234357
TI  - Patterns of nodal relapse after surgery and postoperative radiation therapy for
      carcinomas of the major and minor salivary glands: what is the role of elective
      neck irradiation?
AB  - PURPOSE: To evaluate the incidence of nodal relapses from carcinomas of the
      salivary glands among patients with clinically negative necks in an attempt to
      determine the potential utility of elective neck irradiation (ENI). METHODS AND
      MATERIALS: Between 1960 and 2004, 251 patients with clinically N0 carcinomas of
      the salivary glands were treated with surgery and postoperative radiation
      therapy. None of the patients had undergone previous neck dissection. Histology
      was: adenoid cystic (84 patients), mucoepidermoid (60 patients), adenocarcinoma
      (58 patients), acinic cell (21 patients), undifferentiated (11 patients),
      carcinoma ex pleomorphic adenoma (7 patients), squamous cell (7 patients), and
      salivary duct carcinoma (3 patients); 131 patients (52%) had ENI. Median follow
      up was 62 months (range, 3-267 months). RESULTS: The 5- and 10-year actuarial
      estimates of nodal relapse were 11% and 13%, respectively. The 10-year actuarial
      rates of nodal failure were 7%, 5%, 12%, and 16%, for patients with T1, T2, T3,
      and T4 disease, respectively (p = 0.11). The use of ENI reduced the 10-year nodal
      failure rate from 26% to 0% (p = 0.0001). The highest crude rates of nodal
      relapse among those treated without ENI were found in patients with squamous cell
      carcinoma (67%), undifferentiated carcinoma (50%), adenocarcinoma (34%), and
      mucoepidermoid carcinoma (29%). There were no nodal failures observed among
      patients with adenoid cystic or acinic cell histology. CONCLUSION: ENI
      effectively prevents nodal relapses and should be used for select patients at
      high risk for regional failure.

PMID- 17234358
TI  - Shielding of the hip prosthesis during radiation therapy for heterotopic
      ossification is associated with increased failure of prophylaxis.
AB  - PURPOSE: Radiation therapy (RT) is frequently administered to prevent heterotopic
      ossification (HO) after total hip arthroplasty (THA). The purpose of this study
      was to determine if there is an increased risk of HO after RT prophylaxis with
      shielding of the THA components. METHODS AND MATERIALS: This is a retrospective
      analysis of THA patients undergoing RT prophylaxis of HO at Brigham and Women's
      Hospital between June 1994 and February 2004. Univariate and multivariate
      logistic regressions were used to assess the relationships of all variables to
      failure of RT prophylaxis. RESULTS: A total of 137 patients were identified and
      84 were eligible for analysis (61%). The median RT dose was 750 cGy in one
      fraction, and the median follow-up was 24 months. Eight of 40 unshielded patients
      (20%) developed any progression of HO compared with 21 of 44 shielded patients
      (48%) (p = 0.009). Brooker Grade III-IV HO developed in 5% of unshielded and 18%
      of shielded patients (p = 0.08). Multivariate analysis revealed shielding (p =
      0.02) and THA for prosthesis infection (p = 0.03) to be significant predictors of
      RT failure, with a trend toward an increasing risk of HO progression with age (p
      = 0.07). There was no significant difference in the prosthesis failure rates
      between shielded and unshielded patients. CONCLUSIONS: A significantly increased
      risk of failure of RT prophylaxis for HO was noted in those receiving shielding
      of the hip prosthesis. Shielding did not appear to reduce the risk of prosthesis
      failure.

PMID- 17234359
TI  - Prospective trial of accelerated partial breast intensity-modulated radiotherapy.
AB  - PURPOSE: To examine the feasibility and acute toxicities of an accelerated,
      partial breast, intensity-modulated radiotherapy (IMRT) protocol. METHODS AND
      MATERIALS: Between February 2004 and August 2005, 55 patients with Stage I breast
      cancer and initial follow-up were enrolled at four facilities on a HealthONE and
      Western institutional review board-approved accelerated partial breast IMRT
      protocol. All patients were treated in 10 equal fractions delivered twice daily
      within 5 consecutive days. The first 7 patients were treated to 34 Gy, and the
      remaining 48 patients were treated to 38.5 Gy. RESULTS: The median follow-up
      after IMRT was 10 months (range, <1-19) and after diagnosis was 11.5 months
      (range, 2-21). No local or distant recurrences developed. The T stage
      distribution was as follows: T1a in 11 patients, T1b in 24, and T1c in 20. The
      median tumor size was 9 mm (range, 1-20 mm). Breast cosmesis was judged by the
      patient as poor by 2, good by 12, and excellent by 40 (1 patient was legally
      blind) and by the physician as poor for 1, good for 10, and excellent for 44
      patients. Breast pain, as judged by patient, was none in 34, mild in 19, moderate
      in 2, and severe in 0 patients. There was a single report of telangiectasia but
      no incidents of significant edema. Compared with historic controls for whom three
      dimensional treatment planning techniques were used, IMRT provided similar dose
      delivery to the target while reducing the volume of normal breast included in the
      100%, 75%, and 50% isodose lines. CONCLUSION: This initial report prospectively
      explored the feasibility of accelerated partial breast IMRT. After short-term
      follow-up, the dose delivery and clinical outcomes were very acceptable. We
      believe this regimen deserves additional investigation under institutional review
      board guidance.

PMID- 17234360
TI  - Intensity-modulated radiotherapy for nasopharyngeal carcinoma: clinical
      correlation of dose to the pharyngo-esophageal axis and dysphagia.
AB  - PURPOSE: The aim of this study was to quantify the dose delivered to the pharyngo
      esophageal axis using different intensity-modulated radiation therapy (IMRT)
      techniques for treatment of nasopharyngeal carcinoma and to correlate this with
      acute swallowing toxicity. METHODS AND MATERIALS: The study population consisted
      of 28 patients treated with IMRT between February 2002 and August 2005: 20 with
      whole field IMRT (WF-IMRT) and 8 with IMRT fields junctioned with an anterior
      neck field with central shielding (j-IMRT). Dose to the pharyngo-esophageal axis
      was measured using dose-volume histograms. Acute swallowing toxicity was assessed
      by review of dysphagia grade during treatment and enteral feeding requirements.
      RESULTS: The mean pharyngo-esophageal dose was 55.2 Gy in the WF-IMRT group and
      27.2 Gy in the j-IMRT group, p < 0.001. Ninety-five percent (19/20) of the WF
      IMRT group developed Grade 3 dysphagia compared with 62.5% (5/8) of the j-IMRT
      group, p = 0.06. Feeding tube duration was a median of 38 days for the WF-IMRT
      group compared with 6 days for the j-IMRT group, p = 0.04. CONCLUSIONS: Clinical
      vigilance must be maintained when introducing new technology to ensure that
      unanticipated adverse effects do not result. Although newer planning systems can
      reduce the dose to the pharyngo-esophageal axis with WF-IMRT, the j-IMRT
      technique is preferred at least in patients with no gross disease in the lower
      neck.

PMID- 17234361
TI  - VEGF trap in combination with radiotherapy improves tumor control in u87
      glioblastoma.
AB  - PURPOSE: To determine the effect of vascular endothelial growth factor VEGF Trap
      (Regeneron Pharmaceuticals, Tarrytown, NY), a humanized soluble vascular
      endothelial growth factor (VEGF) receptor protein, and radiation (RT) on tumor
      growth in U87 glioblastoma xenografts in nude mice. METHODS AND MATERIALS: U87
      cell suspensions were implanted subcutaneously into hind limbs of nude mice. VEGF
      Trap (2.5-25 mg/kg) was administered every 3 days for 3 weeks alone or in
      combination with a single dose of 10 Gy or fractionated RT (3 x 5 Gy). In
      addition, three scheduling protocols for VEGF Trap plus fractionated RT were
      examined. RESULTS: Improved tumor control was seen when RT (either single dose or
      fractionated doses) was combined with the lowest dose of VEGF Trap (2.5 mg/kg).
      Scheduling did not significantly affect the efficacy of combined therapy.
      Although high-dose VEGF Trap (10 mg/kg or 25 mg/kg) significantly reduced tumor
      growth over that of RT alone, there was no additional benefit to combining high
      dose VEGF Trap with RT. CONCLUSIONS: Vascular endothelial growth factor Trap plus
      radiation is clearly better than radiation alone in a U87 subcutaneous xenograft
      model. Although high doses of VEGF Trap alone are highly efficacious, it is
      unclear whether such high doses can be used clinically without incurring normal
      tissue toxicities. Thus, information on lower doses of VEGF Trap and ionizing
      radiation is of clinical relevance.

PMID- 17234362
TI  - Long-term outcome after radiotherapy for FIGO stage IIIB and IVA carcinoma of the
      cervix.
AB  - PURPOSE: To report the long-term outcome after radiotherapy with curative intent
      for Stage IIIB and IVA carcinoma of the cervix. METHODS AND MATERIALS: We
      retrospectively reviewed 91 patients treated with radiotherapy with curative
      intent at the University of Florida between January 1980 and December 2003 for
      Stage IIIB (84 patients) or IVA (7 patients) carcinoma of the cervix. RESULTS:
      The median follow-up of the surviving patients was 8.8 years. The 5- and 10-year
      estimates of local control, regional control, locoregional control, relapse-free
      survival, and overall survival were 53% and 53%, 55% and 47%, 34% and 29%, 30%
      and 26%, and 29% and 21%, respectively. Ninety percent of the recurrences
      occurred within 2 years of treatment. Of these, 60% of all failures were local,
      29% were regional, and 11% were distant failures alone. Also, 17% of the failures
      were in the paraaortic nodes with no evidence of failure in the pelvis.
      Univariate and multivariate analyses were conducted with the endpoint of relapse
      free or overall survival. No factor was statistically significant. Complications
      from therapy were scored using the Radiation Therapy Oncology Group grading
      system; the overall severe late complication rate was 13% (Grade 3-5).
      CONCLUSION: This series is one of the most mature of published reports. With long
      term follow-up, approximately one-third of patients with Stage IIIB or IVA
      carcinoma of the cervix were cured, with a 13% complication rate.

PMID- 17234363
TI  - The evolution of aggressive losers.
AB  - We examine the question of when aggressive behavior of likely losers should be
      part of an evolutionarily stable strategy. We modified an earlier model by the
      authors that found situations where likely losers initiate aggressive
      interactions more often than likely winners. The modifications allowed us to
      examine the robustness of the previous study by including an unusually high
      number of possible strategies (n=81) and to examine a wide range of parameter
      settings. First, we show that restricting attention to only a few most plausible
      strategies may change the overall results. Second, within the space where
      escalation is predicted, for a large percentage of the parameter settings (85%),
      an ESS exists that leads to a somewhat counterintuitive situation where
      escalation is more often initiated by the likely loser than by the likely winner
      of the contest. In contrast, an ESS that favors escalation by likely winners was
      found only for about 3% of parameter settings. Furthermore, we use simulations of
      evolution in a finite population to verify for certain parameter settings that
      the analytically predicted ESS's could in fact evolve. Our results suggest that
      ESSs in which the likely loser rather than the likely winner is expected to
      initiate escalation are generic and ESSs in which the opposite is true need to be
      explained by incorporating specific features of the biology of a given species
      into more detailed models.

PMID- 17234364
TI  - Drug fluency: a potential marker for cocaine use disorders.
AB  - The goal of the current study was to tailor semantic fluency to increase its
      sensitivity and ecological validity in the study of drug use disorders. On a
      newly modified "drug" fluency task, individuals with cocaine use disorders who
      tested positive for cocaine at study day named more drug-related words than
      control subjects. The number of words provided on the classical semantic fluency
      task (animals and fruits/vegetables) did not differ between the groups. While the
      individuals with cocaine use disorders who tested negative for cocaine at study
      day did not differ from the control subjects in total words named on this task, a
      qualitative analysis indicated that both cocaine subgroups provided significantly
      more words pertaining to the experience of using drugs (paraphernalia,
      administration) than the matched control subjects. These results demonstrate that
      compared to classical neurocognitive assessment tools, newly tailored measures
      may be more sensitive to cocaine use disorders, psychopathologies that are often
      characterized by mild neuropsychological deficits but a well-circumscribed
      attentional bias to drug-related cues. Future studies are needed to probe the
      exact cognitive processes and neural circuitry underlying performance on this cue
      sensitive 1-min measure.

PMID- 17234365
TI  - Combinations of carbohydrate-deficient transferrin, mean corpuscular erythrocyte
      volume, gamma-glutamyltransferase, homocysteine and folate increase the
      significance of biological markers in alcohol dependent patients.
AB  - AIMS: The traditionally used biological markers for alcoholism include a wide
      range of sensitivity and specificity as single tests. This study focuses on the
      combination of established laboratory parameters with new meaningful biomarkers
      to advance the significance regarding alcohol dependence. DESIGN: We analyzed
      blood samples from alcohol-dependent patients (n=177) compared with a control
      group (n=181). In the statistical calculation we included carbohydrate-deficient
      transferrin (CDT), mean corpuscular erythrocyte volume (MCV), gamma
      glutamyltransferase (GGT), total plasma homocysteine, and folate. RESULTS: None
      of the examined biomarkers reached sensitivity above 90% while all markers showed
      a good specificity. Combinations of different markers led to a significant
      elevation in sensitivity. Best values for men were achieved by using a
      combination of MCV, CDT, GGT, homocysteine and folate in different weightings
      (sensitivity: 98.6%, specificity: 86.4%). For women, similar results were yielded
      by combining MCV and CDT (sensitivity: 94.1%, specificity: 96%). The addition of
      homocysteine and folate in different weightings did not result in further
      enhancement. CONCLUSIONS: Gender-specific clusters including MCV, CDT, GGT,
      homocysteine and folate led to an increase in sensitivity compared to single
      laboratory markers. This is a reliable help to identify patients with regular
      heavy drinking in clinical practice which might prevent further complications.

PMID- 17234366
TI  - Association of CYP2D6 ultrarapid metabolizer genotype with deficient patient
      satisfaction regarding methadone maintenance treatment.
AB  - OBJECTIVE: The activity of cytochrome P-450 enzyme 2D6 (CYP2D6) could be related
      to heroin-dependent patient satisfaction with methadone maintenance treatment. We
      sought to compare satisfaction with the usual methadone treatment in patients who
      are ultrarapid, extensive or poor metabolizers, according to CYP2D6 genotyping.
      METHODS: Two hundred and five heroin-dependent patients filled out the Verona
      Service Satisfaction Scale for methadone maintenance treatment (VSSS-MT), before
      CYP2D6 genotyping. RESULTS: VSSS-MT overall scores were comparable in the poor
      metabolizer (N=9) and extensive metabolizer (N=185) groups, although they were
      higher in poor metabolizers and extensive metabolizers taken together than in the
      ultrarapid metabolizers (N=11) (p<0.003). Likewise, ultrarapid metabolizers
      scored higher than the rest of the sample on the VSSS-MT Basic Interventions
      subscale (p<001). Regarding this subscale, no poor metabolizers felt
      dissatisfied, and ultrarapid metabolizer males (N=7) reported lower satisfaction
      than ultrarapid metabolizer females (N=4) (p<0.022). Ultrarapid metabolizer
      genotype accounted for 4.2% of the variance on the VSSS-MT total scores, and 5.0%
      on the Basic Intervention scores. CONCLUSION: Heroin-dependent patients who are
      CYP2D6 ultrarapid metabolizers according to genotyping present deficient
      satisfaction with methadone maintenance treatment.

PMID- 17234367
TI  - Attenuation of cocaine-seeking by GABA B receptor agonists baclofen and CGP44532
      but not the GABA reuptake inhibitor tiagabine in baboons.
AB  - The current study evaluated the effects of drugs that increase GABA levels by
      activation of GABA(B) receptors (baclofen and CGP44532) or by inhibition of GABA
      reuptake (tiagabine) on the reinstatement of extinguished lever responding
      produced by priming doses of cocaine in baboons (i.e., cocaine-seeking). Cocaine
      self-injection was established and maintained under a fixed ratio (FR10) schedule
      of reinforcement during daily 2h sessions. Lever responding was extinguished by
      substituting vehicle (saline) for cocaine until the number of self-injections
      decreased to 10 or less per session for two consecutive sessions (defined as
      extinction). Once extinction occurred, priming doses of cocaine (0.1-3.2mg/kg,
      i.v.) were administered during extinction conditions. Administration of priming
      doses of cocaine significantly increased cocaine-seeking in a dose-dependent
      manner. Cocaine-seeking produced by priming doses of cocaine were attenuated by
      pretreatment with baclofen (N=5) or CGP44532 (N=5) but not tiagabine (N=3). The
      doses of baclofen (0.32 mg/kg), and CGP445532 (0.32 mg/kg) that reduced cocaine
      seeking produced by cocaine priming doses did not reinstate cocaine-seeking and
      did not produce overt effects when administered alone. These data indicate that
      GABA(B) agonists may reduce relapse to cocaine taking.

PMID- 17234368
TI  - Chemotherapy-related secondary leukemias: A role for DNA repair by error-prone
      non-homologous end joining in topoisomerase II - Induced chromosomal
      rearrangements.
AB  - Chromosome rearrangements are believed to cause the secondary leukemias which
      constitute frequent complications of antitumor chemotherapy with topoisomerase II
      specific drugs. Here we show that inhibition of DNA topoisomerase II in cultured
      cells stimulates association of components of the non-homologous end joining
      system with a known breakpoint cluster region of the human AML1 gene, suggesting
      that errors of DNA repair during NHEJ may be the cause of illegitimate
      recombination in cells treated with topoisomerase II poisons.

PMID- 17234369
TI  - Early detection of cell-free fetal DNA in maternal plasma.
AB  - OBJECTIVES: We aimed to establish the earliest gestational age at which fetal DNA
      in maternal plasma could be detected and whether this was reliable at 12-13
      weeks' gestation. STUDY DESIGN: A prospective observational cohort study of 32
      pregnancies either after IVF or before prenatal diagnosis by CVS. Maternal blood
      was taken and RT-PCR was carried out to detect the multi-copy Y chromosome
      associated DSY14 gene. The end point was gender as assessed at delivery or on
      karyotype. RESULTS: Y signal was obtained as early as 14 days post conception (4
      weeks' gestation) and has a good prediction rate by 12 weeks' gestation.
      CONCLUSION: Free fetal DNA allows very early prediction of fetal sex in some
      cases and could be useful for clinical use for X-linked conditions by the end of
      the first trimester.

PMID- 17234370
TI  - Cell uptake, cytoplasmic diffusion and nuclear access of a 6.5 nm diameter
      dendrimer.
AB  - Macromolecular crowding and the presence of organelles in the cytosol present
      barriers to particle mobility, such that it is unclear how nano-carriers can
      deliver their active agents to the nucleus. In this work a sixth generation amino
      terminated polyamide polylysine dendrimer (Gly-Lys(63) (NH(2))(64)) (MW 8149,
      diameter 6.5 nm) which is fluorescent allowed the study of nuclear uptake and
      mobility in living lung carcinoma (SK/MES-1) and colon adenocarcinoma (Caco-2)
      cells. The dendrimer is found within 25-45 min of incubation inside the cell
      nuclei. Living cells were then used to develop a method for the dynamic nuclear
      uptake study using confocal microscopy. The dynamic uptake of the dendrimer
      demonstrated here allowed the apparent cytoplasmic diffusion coefficient (D) of
      the dendrimer to be calculated. Values were found in the range 5.99 x 10(
      11)cm(2)s(-1) (SK/MES-1 cells) to 9.82 x 10(-11)cm(2)s(-1) (Caco-2 cells). The
      difference must reflect variation in the intracellular architecture of the cell
      types.

PMID- 17234371
TI  - Synthesis and characterization of grafted thermosensitive hydrogels for heating
      activated controlled release.
AB  - Poly(N-isopropylacrylamide), PNIPAAm, hydrogels are negatively thermosensitive
      which means that they have an expanded hydrogel structure at low temperatures and
      a shrunken structure at high temperatures. Based on this negative
      thermosensitivity of PNIPAAm, a drug delivery system with PNIPAAm oligomers
      grafted onto poly(hydroxyethyl methacrylate) PHEMA, a thermally nonresponsive
      polymer was designed. Poly(hydroxyethyl methacrylate-g-N-isopropylacrylamide),
      P(HEMA-g-NIPAAm) hydrogels were synthesized to control the release of an imbedded
      drug. This new grafted system exhibited high diffusivity at temperatures greater
      than the lower critical solution temperature (LCST) of the PNIPAAm oligomers.
      Utilizing PNIPAAm's LCST of approximately 34 degrees C, the release rate was
      controlled by the temperature of the release medium. The LCST of PNIPAAm was
      tuned by making copolymers with hydrophobic butyl methacrylate (BMA).
      Theophylline and inulin release profiles were studied using PHEMA, PNIPAAm and
      P(HEMA-g-NIPAAm) at three temperatures with drug diffusion coefficients
      determined as a function of temperature and drug type. The molecular weights
      between crosslinks and mesh sizes of PHEMA hydrogels were calculated using Flory
      Rehner and rubber-elasticity theories.

PMID- 17234372
TI  - Enhanced desensitization efficacy by liposomal conjugation of a specific antigen.
AB  - Since liposomes are known as strong adjuvants, we attempted to use liposomes in
      immunotherapy as adjuvants, and to achieve desensitization in pre-sensitized
      mice. At first, we sensitized mice with intraperitoneal injection of model
      antigen, 100 microg ovalbumin (OVA), with Alum and treated them with liposome
      composed of distearoylphosphatidylcholine (DSPC) and cholesterol (2:1 as a molar
      ratio), which was coupled with a small amount of OVA (10 microg OVA in 400 nmol
      DSPC and 200 nmol cholesterol-liposome was injected into 20 g mouse). It is well
      known that antigen-specific immunotherapy increases IgG blocking antibodies and
      decreases in IgE antibodies. The treatment with i.v. injection of OVA-liposome at
      days 8, 10, and 12 after sensitization strongly suppressed OVA-specific IgE
      production without affecting IgG level after the boost (100 microg OVA with
      Alum). Moreover, the treatment with high-density OVA-liposome (10 microg OVA in
      80 nmol DSPC and 40 nmol cholesterol-liposome/20 g mouse) not only strongly
      suppressed IgE levels but also reduced IgG production after the boost of OVA
      sensitized mice suggesting the importance of liposomal characteristic in
      desensitization immunotherapy. Next we reduced the dose of OVA-liposome and the
      desensitization effect was also observed at the dose of as low as 1 microg OVA on
      OVA-liposome/mouse. On the contrary, free OVA did not affect the production of
      both IgG and IgE levels. Biodistribution study indicated that OVA-liposome was
      highly accumulated in spleen of OVA-sensitized mice compared to control liposome
      at 3 h after i.v. injection. These results suggest that the liposomal OVA
      effectively interacts with and desensitizes immune cells, therefore, liposomes
      coupling with a certain antigen may be effective in allergy immunotherapy.

PMID- 17234373
TI  - Antileishmanial and antifungal activity of plants used in traditional medicine in
      Brazil.
AB  - The antileishmanial and antifungal activity of 24 methanol extracts from 20
      plants, all of them used in the Brazilian traditional medicine for the treatment
      of several infectious and inflammatory disorders, were evaluated against
      promastigotes forms of two species of Leishmania (L. amazonensis and L. chagasi)
      and two yeasts (Candida albicans and Cryptococcus neoformans). Among the 20
      tested methanolic extracts, those of Vernonia polyanthes was the most active
      against L. amazonensis (IC(50) of 4 microg/ml), those of Ocimum gratissimum
      exhibited the best activity against L. chagasi (IC(50) of 71 microg/ml).
      Concerning antifungical activity, Schinus terebintifolius, O. gratissimum,
      Cajanus cajan, and Piper aduncum extracts were the most active against C.
      albicans (MIC of 1.25 mg/ml) whereas Bixa orellana, O. gratissimum and Syzygium
      cumini exhibited the best activity against C. neoformans (MIC of 0.078 mg/ml).

PMID- 17234374
TI  - Saussurea lappa inhibits the growth, acid production, adhesion, and water
      insoluble glucan synthesis of Streptococcus mutans.
AB  - In the present study, inhibitory effects of the ethanol extract of Saussurea
      lappa (S. lappa) on the growth, acid production, adhesion, and water-insoluble
      glucan synthesis of Streptococcus mutans (S. mutans) were examined. The growth
      and acid production of Streptococcus mutans were inhibited by the presence of
      ethanol extract of Saussurea lappa (0.5-4 mg/ml) significantly. The ethanol
      extract of Saussurea lappa (0.25-4 mg/ml) also significantly lowered the
      adherence of Streptococcus mutans in a dose dependent manner. In water-insoluble
      glucan synthesis assay, 2-4 mg/ml of the ethanol extract of Saussurea lappa
      significantly inhibited the formation of water-insoluble glucan. These results
      suggest that Saussurea lappa may inhibit the caries-inducing properties of
      Streptococcus mutans. Further studies are necessary to clarify the active
      constituents of Saussurea lappa responsible for such biomolecular activities.

PMID- 17234375
TI  - Evaluation of antiplasmodial activity of ethanolic seed extract of Picralima
      nitida.
AB  - The in vivo antiplasmodial activity of the ethanol seed extract of Picralima
      nitida grown particularly for the leaf and seed in Niger Delta region of Nigeria
      was evaluated in Plasmodium berghei berghei infected mice. Picralima nitida (35
      115 mg/kg day) exhibited significant (P<0.05) blood schizonticidal activity both
      in 4-day early infection test and in established infection with a considerable
      mean survival time though not comparable to that of the standard drug,
      chloroquine, 5 mg/kg day. The seed extract possesses significant (P<0.05)
      antiplasmodial activity which correlate with it reported in vitro activity.

PMID- 17234376
TI  - Antifungal activity of Brazilian medicinal plants involved in popular treatment
      of mycoses.
AB  - A survey of medicinal plants used to treat common mycoses was done in the
      Curituba district, Sergipe State, Brazil. One hundred inhabitants were
      interviewed by health agents and traditional healers. Four different plants were
      the most cited (more than 50% of the citations): Ziziphus joazeiro, Caesalpinia
      pyramidalis, Bumelia sartorum and Hymenea courbaril. The aqueous extracts
      obtained following traditional methods and using different parts of these plants,
      were submitted to drop agar diffusion tests for primary antimicrobial screening.
      Only the water infusion extract of Ziziphus joazeiro and Caesalpinea pyramidalis
      presented a significant antifungal activity against Trichophyton rubrum, Candida
      guilliermondii, Candida albicans, Cryptococcus neoformans and Fonsecaea pedrosoi,
      when compared to the antifungal agent amphotericin B. The minimal inhibitory
      concentration (MIC) of the bioactive extracts was evaluated by the microdilution
      method. Best activity with a MIC of 6.5 microg/ml for both extracts was observed
      against Trichophyton rubrum and Candida guilliermondii. Ziziphus joazeiro and
      Caesalpinea pyramidalis extracts presented also low acute toxicity in murine
      models. The present study validates the folk use of these plant extracts and
      indicates that they can be effective potential candidates for the development of
      new strategies to treat fungal infections.

PMID- 17234377
TI  - Impact of sonography in gouty arthritis: comparison with conventional
      radiography, clinical examination, and laboratory findings.
AB  - OBJECTIVE: To explore the typical sonographic features of gray-scale and Power
      Doppler of acute and chronic gouty arthritis in conjunction with radiographic,
      clinical, and laboratory findings. MATERIALS AND METHODS: All hand, finger, and
      toe joints of 19 patients with acute and chronic gout were examined with gray
      scale and Power Doppler sonography. The number and size of bone changes detected
      with sonography was compared to radiographic findings. Vascularization of the
      synovial tissue was scored on Power Doppler (grades 0-3), and was compared with
      clinical appearance, including swelling, tenderness, and redness (grades 0-3).
      RESULTS: In acute gout, mild to moderate echogenic periarticular nodules with
      sonotransmission and hypervascularization of the edematous surrounding soft
      tissue were found. In chronic gout, tophaceous nodules completely blocked
      transmission of US wave, leading to strong reflexion and dorsal shadowing in a
      minority of cases. No significant difference in the detection of large bone
      changes (>2mm) was found between sonography and radiography. However, gray-scale
      sonography was significantly more sensitive in the detection of small bone
      changes (p<0.001). Power Doppler scores were statistically significantly higher
      than clinical examination scores (p<0.001). DISCUSSION: Sonography is superior to
      radiographs in evaluating small bone changes. The inflammatory process in joints
      can be better detected with Power Doppler sonography than with clinical
      examination. Typical sonographic appearance of acute and in particular of chronic
      gout might provide clues on gouty arthritis that adds to the information
      available from conventional radiography, clinical, and laboratory findings.

PMID- 17234378
TI  - The three classes of triplet profiles of natural genomes.
AB  - Based on the huge variety of different genomes, one may expect a correspondingly
      large variety of the frequency distribution of their trinucleotides ("triplet
      profiles"). Yet, this article reports the unexpected finding that there are
      essentially only three kinds of triplet profiles among the large number of
      genomes examined here. None of the classes included random profiles, all of them
      contained members from vastly different taxa and species. Since the three classes
      of genomes do not reflect the phylogeny of their member organisms, I propose that
      these classes may reflect species-independent mechanisms of genome evolution.

PMID- 17234379
TI  - -G308A tumor necrosis factor alpha functional polymorphism and schizophrenia
      risk: meta-analysis plus association study.
AB  - Research on -G308A functional polymorphism in the tumor necrosis factor alpha
      (TNFalpha) gene as a susceptibility factor for schizophrenia has provided
      contrasting results in different populations. Therefore we conducted a meta
      analysis of the published case-control association studies and a replication
      study in a large sample. Meta-analyses (total sample: 2512 cases versus 3223
      controls) showed that the AA genotype was weakly associated with schizophrenia
      susceptibility in Caucasoids (Odd Ratio OR=1.65, 95% CI=1.00-2.71 Z=1.98 p=0.05).
      The replication case-control association study (323 DSM-IV-TR schizophrenia
      patients and 346 controls) showed that the A allele conferred an increased
      susceptibility for schizophrenia only in males (OR=1.73, 95% CI=1.07-2.79,
      p=0.025), and the association became more specific when only patients of the
      paranoid subtype were compared to the controls (relative risk ratio=3.09, 95%
      CI=1.28-7.47, p=0.012). The presence of the A allele was also associated with a
      later age at onset of schizophrenia in the whole sample (F(1,291)=7.094,
      p=0.008). Our results confirm that TNFalpha A allele could have an effect on
      vulnerability to schizophrenia but further studies revaluating the role of gender
      and diagnostic subtypes are necessary to confirm these findings.

PMID- 17234380
TI  - Perspective is everything: an irreverent discussion of CNS-immune system
      interactions as viewed from different scientific traditions.
AB  - The immune system is a host defense system comprised of both innate mechanisms
      able to rapidly recognize and respond to conserved pathogen associated molecular
      patterns (PAMPs) as well as adaptive mechanisms able to respond to a wide variety
      of non-conserved and conserved pathogen associated molecules. In vitro and in
      vivo studies have demonstrated that the kinetics and type of immune response
      triggered by pathogenic insults is a function of both the nature of the insult
      and the subsequent cross-regulatory interactions between the responding immune
      cells. In this context, the potential immunomodulatory influences of the nervous
      system have been often viewed as exerting minimal modulatory effects and thus of
      being largely irrelevant in the development of immune responses. Here, using a
      Saturday Night Live (SNL)-styled point:counterpoint format, we discuss whether
      and to what extent the nervous system can shape the responses of the immune
      system. Finally, we examine whether primary degenerative disorders of the CNS are
      likely to lead to alterations in immune function.

PMID- 17234381
TI  - Assessment of reproductive toxicity of orally administered technical dimethoate
      in male mice.
AB  - The effect of organophosphate insecticide dimethoate at three dosage levels (7,
      15, and 28 mg/kg/day) on male reproduction in mice was studied. Dimethoate was
      given orally by gavage to male mice for 20 days before mating with untreated
      females. Signs of cholinergic effects were observed in the 15 and 28 mg/kg/day
      treated groups. Brain and skeletal muscle acetylcholinesterase activities were
      inhibited in both the middle and high dose groups. Dimethoate was associated with
      a decreased number of implantations and live fetuses, and an increased number of
      dead and early resorptions at 28 mg/kg/day treated group. The percent
      morphologically normal spermatozoa were unaffected in any of dose groups.
      However, sperm production and percent motile sperm were decreased in the 15 and
      28 mg/kg/day treated groups compared to the control. Histological changes in
      testis were observed in the middle and high treated groups. The current study
      demonstrated the adverse effects of dimethoate on the reproductive performance of
      male mice and pregnancy outcomes following mating with untreated female mice at
      dose levels of 15 and 28 mg/kg/day. The No Observed Effect Level (NOEL) in the
      present study for reproductive performance was 7 mg/kg/day.

PMID- 17234382
TI  - Nicotine causes age-dependent changes in gene expression in the adolescent female
      rat brain.
AB  - Humans often start smoking during adolescence. Recent results suggest that
      rodents may also be particularly vulnerable to nicotine dependence during
      adolescence. We examined the effect of chronic nicotine exposure on gene
      expression profiles during adolescence in female rats, who were dosed with
      nicotine (and control animals were dosed with saline) via subcutaneously
      implanted osmotic minipumps. Brain samples were collected at four ages: before
      puberty (postnatal day 25), at about the time of puberty in females (postnatal
      day 35), and after puberty (postnatal days 45 and 55). The expression of 7931
      genes in three brain areas was measured using DNA microarrays. Quantitative RT
      PCR was also employed to confirm the expression patterns of selected genes. We
      used a novel clustering technique (principal cluster analysis) to classify 162
      nicotine-regulated genes into five clusters, of which only one (cluster A) showed
      similar patterns of gene expression across all three brain areas (ventral
      striatum, prefrontal cortex, and hippocampus). Three clusters of genes (A, B, and
      C) showed dramatic peaks in their nicotine responses at the same age (p35). The
      other two clusters (D1 and D2) showed smaller peaks and/or valleys in their
      nicotine responses at p35 and p45. Thus, the age of maximal gene expression
      response to nicotine in female rats corresponds approximately to the age of
      maximal behavioral response and the age of puberty.

PMID- 17234384
TI  - Self-organizing maps with dynamic learning for signal reconstruction.
AB  - Wireless Brain Machine Interface (BMI) communication protocols are faced with the
      challenge of transmitting the activity of hundreds of neurons which requires
      large bandwidth. Previously a data compression scheme for neural activity was
      introduced based on Self Organizing Maps (SOM). In this paper we propose a
      dynamic learning rule for improved training of the SOM on signals with sparse
      events which allows for more representative prototype vectors to be found, and
      consequently better signal reconstruction. This work was developed with BMI
      applications in mind and therefore our examples are geared towards this type of
      signals. The simulation results show that the proposed strategy outperforms
      conventional vector quantization methods for spike reconstruction.

PMID- 17234383
TI  - Prenatal cocaine exposures and dose-related cocaine effects on infant tone and
      behavior.
AB  - BACKGROUND: In experimental models, prenatal cocaine exposure has been found to
      perturb monoaminergic development. In humans, numerous studies have sought
      clinical correlates, but few have focused on dose-related effects, especially as
      regards neurologic function beyond the neonatal period. OBJECTIVE: To assess
      whether prenatal cocaine exposure has adverse effects on infant neurologic,
      developmental and behavioral outcomes and whether any effects are dose-dependent.
      DESIGN/METHODS: Infants (398) were enrolled at birth from an urban hospital. Drug
      exposure was ascertained with biomarkers in hair (n=395), urine (n=170) and
      meconium (n=109). Children were followed prospectively and 286 (72%) were
      evaluated blind to drug exposure at 6 months of age with the Bayley scales, Fagan
      Scale of Infant Intelligence and a standardized neurological examination.
      RESULTS: Certain neurological findings increased significantly by the amount of
      cocaine detected in maternal hair, e.g. abnormality of tone, as indicated by
      extensor posture was detected among 28% of cocaine-unexposed infants, 43% of
      infants exposed to lower and 48% exposed to higher cocaine levels in maternal
      hair (p<0.009). Persistent fisting increased in a similar dose-dependent manner.
      These associations persisted in adjusted analyses. Prenatal cocaine exposure was
      not associated with developmental scores (mental, motor or novelty preference)
      but was associated with lower orientation scores in adjusted analyses.
      CONCLUSIONS: At 6 months of age, prenatal cocaine exposure was associated with
      abnormalities of tone and posture and with lower orientation scores.
      Perturbations in monoaminergic systems by cocaine exposure during fetal
      development may explain the observed neurological and behavioral symptoms.
      Whether such findings in infancy increase the risk of later neurobehavioral
      problems requires further study.

PMID- 17234385
TI  - Efficiently updating and tracking the dominant kernel principal components.
AB  - The dominant set of eigenvectors of the symmetrical kernel Gram matrix is used in
      many important kernel methods (like e.g. kernel Principal Component Analysis,
      feature approximation, denoising, compression, prediction) in the machine
      learning area. Yet in the case of dynamic and/or large-scale data, the batch
      calculation nature and computational demands of the eigenvector decomposition
      limit these methods in numerous applications. In this paper we present an
      efficient incremental approach for fast calculation of the dominant kernel
      eigenbasis, which allows us to track the kernel eigenspace dynamically.
      Experiments show that our updating scheme delivers a numerically stable and
      accurate approximation for eigenvalues and eigenvectors at every iteration in
      comparison to the batch algorithm.

PMID- 17234386
TI  - Detection of CTX-M-15 and CTX-M-33, a novel variant of CTX-M-15, in clinical
      Escherichia coli isolates in Greece.

PMID- 17234387
TI  - A significant correlation between ward temperature and the severity of symptoms
      in schizophrenia inpatients--a longitudinal study.
AB  - BACKGROUND: Preliminary data suggest that schizophrenia outpatients' mental
      status might be affected, at least to some extent, by environmental temperature.
      To further substantiate the potential role of environmental temperature and
      schizophrenic symptoms we examined, in a naturalistic design, the relationship
      between environmental temperature of schizophrenia inpatients (i.e., ward
      temperature) and their mental status. METHODS: Mean daily temperature of a closed
      psychiatric ward was monitored for 32 consecutive weeks. Temperature assessments
      were performed at 3 different locations within the ward at the same hour daily.
      Mean daily temperature was defined as the average of the 3 values. During each of
      the 32 weeks of the study, the inpatients were divided into two sub-groups:
      schizophrenia patients (n=22-34 patients/week) and non-schizophrenia psychotic
      patients (n=5-12 patients/week). The mental status of all participants was
      evaluated weekly using the positive and negative syndrome scale (PANSS). All
      participants were treated with antipsychotics during the entire study period.
      RESULTS: Schizophrenia patients' total PANSS score, as well as each of the PANSS'
      subscales (positive, negative, general psychopathology, depression) were
      positively and significantly correlated with ward temperature (r=0.52-0.64;
      p=0.002-0.0001). No correlation was found between ward temperature and any of the
      PANSS' subscales in the non-schizophrenia psychotic subjects. CONCLUSION: Our
      results suggest that schizophrenia inpatients' mental status might be modulated,
      at least to some extent, by environmental (i.e., ward) temperature and that this
      phenomenon is specific to schizophrenia patients. Our findings imply the need for
      optimally adjusting ward temperature (e.g., about 19 degrees C in this study) for
      the management of patients with acute psychotic exacerbation of schizophrenia.

PMID- 17234388
TI  - Effects of the 5-HT1B receptor antagonist NAS-181 on extracellular levels of
      acetylcholine, glutamate and GABA in the frontal cortex and ventral hippocampus
      of awake rats: a microdialysis study.
AB  - The purpose of this study was to investigate the effects of the 5-HT(1B) receptor
      antagonist NAS-181 ((R)-(+)-2-(3-morpholinomethyl-2H-chromen-8-yl) oxymethyl
      morpholine methanesulfonate) on cholinergic, glutamatergic and GABA-ergic
      neurotransmission in the rat brain in vivo. Extracellular levels of
      acetylcholine, glutamate and GABA were monitored by microdialysis in the frontal
      cortex (FC) and ventral hippocampus (VHipp) in separate groups of freely moving
      rats. NAS-181 (1, 5 or 10 mg/kg, s.c.) caused a dose-dependent increase in ACh
      levels, reaching the maximal values of 500% (FC) and 230% (VHipp) of controls at
      80 min post-injection. On the contrary, NAS-181 injected at doses of 10 or 20
      mg/kg s.c. had no effect on basal extracellular levels of Glu and GABA in these
      areas. The present data suggest that ACh neurotransmission in the FC and VHipp,
      the brain structures strongly implicated in cognitive function, is under tonic
      inhibitory control of 5-HT(1B) heteroreceptors localized at the cholinergic
      terminals in these areas.

PMID- 17234389
TI  - A 6-month prospective, observational, naturalistic, uncontrolled study to
      evaluate the effectiveness and tolerability of oral ziprasidone in patients with
      schizophrenia.
AB  - This multicenter, uncontrolled, naturalistic study evaluated the effectiveness
      and tolerability of 6 months of treatment with ziprasidone in 1266 patients with
      a diagnosis of schizophrenia. The percentage of responders (at least 30%
      reduction in PANSS total score) in the primary analysis sample (n=1022) was 47.3%
      (95% CI 44.2-50.4) at the end of the study. Patients showed a significant and
      clinically relevant reduction in the PANSS total, positive, negative and general
      psychopathology subscales scores (effect size of 1.60, 1.83, 0.62 and 1.40
      respectively). Overall, 453 (35.8%) patients withdrew from the study; 9.3%
      withdrew owing to adverse events. Ziprasidone doses greater than 120 mg/day were
      associated with a lower risk of discontinuation for any cause (OR 0.46, 95% CI
      0.33-0.65) Ziprasidone was well tolerated. Most common side effects were:
      insomnia, somnolence and nervousness. The effectiveness and tolerability of
      ziprasidone in clinical practice are consistent to those previously shown in the
      more restricted and homogeneous populations of clinical trials.

PMID- 17234390
TI  - Hydrolytic cleavage of DNA by quercetin manganese(II) complexes.
AB  - Quercetin manganese(II) complexes were investigated focusing on its DNA
      hydrolytic activity. The complexes successfully promote the cleavage of plasmid
      DNA, producing single and double DNA strand breaks. The amount of conversion of
      supercoiled form (SC) of plasmid DNA to the nicked circular form (NC) depends on
      the concentration of the complex as well as the duration of incubation of the
      complexes with DNA. The maximum rate of conversion of the supercoiled form to the
      nicked circular form at pH 7.2 in the presence of 100 microM of the complexes is
      found to be 1.32 x 10(-4) s(-1). The hydrolytic cleavage of DNA by the complexes
      was supported by the evidence from free radical quenching, thiobarbituric acid
      reactive substances (TBARS) assay and T4 ligase ligation.

PMID- 17234391
TI  - Effect of Lactobacillus challenge on Gardnerella vaginalis biofilms.
AB  - Bacterial vaginosis (BV) is the most common infectious condition in women. It is
      caused primarily by anaerobic bacteria which rapidly form biofilms recalcitrant
      to antibiotic treatment, elevate vaginal pH, induce inflammatory processes and
      displace indigenous lactobacilli from the vault. Gardnerella vaginalis is
      commonly associated with these infections. Microscopy analysis showed that within
      72 h, viable G. vaginalis covered a surface area of 567 microm(2), reached a
      depth of 16 microm and a density of approximately 104 microm(3). They maintained
      these levels for a further 3 days unless challenged with lactobacilli strains.
      Lactobacillus reuteri RC-14 produced the biggest displacement of Gardnerella.
      This was not due to pH, which remained between 4.7 and 5.1 for all experiments,
      nor by hydrogen peroxide which is produced in low amounts by strain L. reuteri RC
      14, high amounts by L. crispatus 33820 and not at all by L. rhamnosus GR-1.
      Deconvolution microscopy showed changes in structure and viability of the
      biofilms, with loss of dense Gardnerella biofilm pods. For the first time, a
      strain of L. iners, the most commonly isolated vaginal Lactobacillus in healthy
      women, was tested for potential probiotic properties. It was found to disrupt
      Gardnerella biofilm surface area, density and depth, albeit to a lesser extent
      than L. reuteri RC-14. These studies help to provide insight into the clinical
      situation in which probiotic and indigenous vaginal lactobacilli can interfere
      with Gardnerella's presence and reduce the risk of bacterial vaginosis.

PMID- 17234392
TI  - Immobilization of liposomes on hydrophobically modified polymer gel particles in
      batch mode interaction.
AB  - Immobilization of liposomal phospholipids onto Sephacryl S-1000 gels that were
      chemically conjugated with hydrophobic alkyl moieties, octyl, dodecyl and
      hexadecyl, was examined in batch mode interaction. Compared with the octyl gel,
      the dodecyl and the hexadecyl gels were found to immobilize the three to four
      times more phospholipids with the less hydrophobic moieties. The encapsulation of
      a water-soluble marker, with other evidences, suggests that the majority of the
      immobilized phospholipids maintained liposomal morphology. As the lipid of the
      interacting liposomes, egg yolk phosphatidylcholine (eggPC), 1,2
      dimyristoylphosphatidylcholine (DMPC) and a mixture of DMPC and 1,2-dimyristamido
      1,2-deoxyphosphatidylcholine were examined. At 22 degrees C, DMPC liposomes
      showed higher extent of immobilization than at 37 degrees C but not eggPC
      liposomes, suggesting that the phase of liposomal membrane could have influence
      on the immobilization. Exchange between the immobilized liposomes and free ones
      was found to be small, less than 3%. The gel that had been first interacted with
      liposomes to apparent saturation could further immobilize the newly added
      liposomes. The rate of this second immobilization was similar to that of the slow
      adsorption process; the both could be based on the same mechanism, possibly
      involving rearrangement of the immobilized liposomes on the gel as proposed by
      Lundahl. As had been observed in the flow mode, the immobilization had preference
      for smaller liposomes. In application of the system in batch mode, the size
      distributions of the immobilized liposomes and of those left in the supernatant
      may differ from that of the originally added liposomes.

PMID- 17234393
TI  - Formation of colloidal suspension of hydrophobic compounds with an amphiphilic
      self-assembling peptide.
AB  - The amphiphilic self-assembling peptide EAK16-II was found to be able to
      stabilize hydrophobic compounds in aqueous solution. Micro/nanocrystals of a
      hydrophobic compound, pyrene, and a hydrophobic anticancer agent, ellipticine,
      were stabilized by EAK16-II to form colloidal suspensions in water. Initial
      evidence of the association between EAK16-II and hydrophobic compounds was the
      observation of a clouding phenomenon and a difference in fluorescence spectra of
      the solution. A further investigation on the interaction between EAK16-II and
      pyrene was carried out using fluorescence spectroscopy and scanning electron
      microscopy (SEM). It was found that the pyrene-peptide complex formation required
      mechanical stirring, and the freshly prepared peptide solution (containing
      peptide monomers and/or peptide protofibrils) was more effective at stabilizing
      pyrene than the mature fibrils in aged peptide solutions. The time duration over
      which the complex formed was about 22 h. The data on the complexation of pyrene
      and EAK16-II at various concentrations suggested that the maximum amount of
      stabilized pyrene was concentration dependent. SEM images showed that peptide
      concentration did not significantly affect the size of the complexes/suspensions
      but altered the structures of the peptide coating on the surface of the complex.
      Atomic force microscopy (AFM) was conducted to study the interaction of EAK16-II
      with a model hydrophobic surface, which provided some detailed information of how
      peptide adsorbed onto the hydrophobic compounds and stabilize them. This study
      shows the potential of self-assembling peptides for encapsulation of hydrophobic
      compounds.

PMID- 17234394
TI  - Synthesis of amphiphilic poly(ether-amide) dendrimer endcapped with poly(ethylene
      glycol) grafts and its solubilization to salicylic acid.
AB  - An amphiphilic dendrimer (DPEA-PEG) grafting polyethylene glycol at the terminals
      was prepared by endcapping of dendritic poly(ether-amide) (DPEA) with isocyanate
      terminated linear polyethylene glycol (PEG-NCO). The molecular structure was
      verified by gel permeation chromatography (GPC), (1)H NMR and FT-IR. The micelle
      characteristic of DPEA-PEG in water was investigated. The critical micelle
      concentration (CMC) was determined by a fluorescence technique to be 55.5 mg/L.
      The hydrodynamic radius of micelles was measured by dynamic light scattering
      (DLS) to be 76.2 nm. The UV-vis spectrum showed that the solubility of salicylic
      acid increased from 1.91 to 2.78 mg/L when the concentration of DPEA-PEG attained
      5 mg/mL in an aqueous solution.

PMID- 17234395
TI  - Stable carbamazepine colloidal systems using the cosolvent technique.
AB  - The aim of this paper was to prepare stable carbamazepine nanosuspensions
      containing 10mg/ml drug concentration by screening different polymers. Stable
      formulations were created by the cosolvent technique with polyethylene glycol
      (PEG-300) and water as the cosolvents. Rapid growth of long needle shaped CBZ
      crystals was observed in the absence of polymer. The presence of hydroxypropyl
      methylcellulose (HPMC) or methylcellulose (MC) inhibited crystal growth and the
      mean particle sizes were in the range 10-20 nm. Simultaneous presence of HPMC and
      polyvinylpyrrolidon (PVP PF17) polymers in CBZ suspensions enhanced the overall
      stability of the formulations. The additional stability improvement was
      attributed to the interaction between the polymers by the formation of hydrogen
      bonds. Suspension stability was evaluated over 5 months where the particle size
      remained constant. FT-Raman studies showed the existence of form I within the
      stable CBZ suspensions.

PMID- 17234396
TI  - Decreased tumor growth in Walker 256 tumor-bearing rats chronically supplemented
      with fish oil involves COX-2 and PGE2 reduction associated with apoptosis and
      increased peroxidation.
AB  - Many studies have shown that addition of fish oil (FO) to the diet reduces tumor
      growth but the mechanism(s) of action involved is (are) still unknown. In this
      study, we examine some possible mechanisms in tumor-bearing rats chronically
      supplemented with FO. Male Wistar rats (21 days old) were fed with regular chow
      and supplemented with coconut or FO (1g/kg body weight) until they reached 70
      days of age. Then, they were inoculated with a suspension of Walker 256 ascitic
      tumor cells (2 x 10(7)ml) and after 14 days they were killed. Supplementation
      with FO resulted in significantly lower tumor weight, greater tumor cell
      apoptosis, lower ex vivo tumor cell proliferation, a higher tumor content of
      lipid peroxides, lower expression of cyclooxygenase-2 (COX-2) in tumor tissue and
      a lower plasma concentration of prostaglandin E2 than observed in rats fed
      regular chow or supplemented with coconut oil. These results suggest that
      reduction of tumor growth by FO involves an increase in apoptosis and of lipid
      peroxidation in tumor tissue, with a reduction in tumor cell proliferation ex
      vivo, COX-2 expression and PGE2 production. Thus, FO may act simultaneously
      through multiple effects to reduce tumor growth. Whether these effects are
      connected through a single underlying mechanism remains to be seen.

PMID- 17234397
TI  - Airway nitric oxide output is reduced in bronchiectasis.
AB  - BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) have been
      detected in inflammatory lung diseases including asthma and have been attributed
      to increased expression and activity of inducible nitric oxide synthase (iNOS)
      within the airways. However, previous studies of exhaled NO in patients with
      bronchiectasis have yielded conflicting results, with reports of both increased
      and normal NO values. Recent evidence from animal models suggests that chronic
      airway infection reduces NO production within the lung, despite causing increased
      iNOS expression. We tested the hypothesis that, in human subjects with
      bronchiectasis, chronic airway infection reduces NO output from the conducting
      airways. METHODS: Using a recently described two-compartment model, we measured
      separately the contributions of the conducting airways and the alveoli to exhaled
      NO in nine patients with stable bronchiectasis and eight control subjects before
      and after inhaled glucocorticoid therapy. RESULTS: We found that airway NO output
      was significantly lower in bronchiectasis than in normal airways whereas NO
      output from the alveoli was similar to that of control subjects. High-dose
      inhaled glucocorticoid therapy did not alter airway or alveolar NO production.
      CONCLUSIONS: These findings demonstrate that, in patients with bronchiectasis,
      airway NO output is reduced and that iNOS does not contribute significantly to
      airway NO production.

PMID- 17234398
TI  - Emerging approaches for imaging vulnerable plaques in patients.
AB  - The diagnosis of vulnerable plaques, which have the propensity to develop
      atherothrombosis, remains an elusive goal in clinical medicine. The most accepted
      features of vulnerable plaques, such as a large lipid core, increased
      inflammatory milieu and thin fibrous caps, have been well characterized through
      pathological studies. The ability to image a vulnerable plaque in susceptible
      patients would theoretically result in useful prognostic information that can be
      used to either monitor or treat patients at risk more aggressively. Several
      invasive techniques, such as integrated backscatter, virtual histology,
      palpography, optical coherence tomography and thermal heterogeneity, have been
      validated ex vivo and are now being evaluated in clinical studies. Non-invasive
      techniques, such as nuclear imaging, show promise in identifying increased
      metabolic activity and characteristic features of vulnerable plaques in patients.
      Natural history and intervention studies will need to be performed to determine
      whether identifying and treating vulnerable plaques will lead to improved
      clinical outcomes.

PMID- 17234399
TI  - Fluorescence imaging in vivo: recent advances.
AB  - In vivo fluorescence imaging uses a sensitive camera to detect fluorescence
      emission from fluorophores in whole-body living small animals. To overcome the
      photon attenuation in living tissue, fluorophores with long emission at the near
      infrared (NIR) region are generally preferred, including widely used small
      indocarbocyanine dyes. The list of NIR probes continues to grow with the recent
      addition of fluorescent organic, inorganic and biological nanoparticles. Recent
      advances in imaging strategies and reporter techniques for in vivo fluorescence
      imaging include novel approaches to improve the specificity and affinity of the
      probes and to modulate and amplify the signal at target sites for enhanced
      sensitivity. Further emerging developments are aiming to achieve high-resolution,
      multimodality and lifetime-based in vivo fluorescence imaging.

PMID- 17234400
TI  - Role of activity-dependent regulation of neuronal chloride homeostasis in
      development.
AB  - The polarity of neurotransmission mediated by the gamma-amino butyric acid (GABA)
      type A receptor depends crucially on intracellular chloride concentration, which
      is largely determined by the expression and function of cation/chloride co
      transporters. Recent evidence shows how both activity and neurotrophic factors
      can affect GABAergic transmission in the mammalian central nervous system through
      their effects on the neuron-specific chloride-extruding transporter KCC2. In
      particular, GABAergic neurotransmission early in development, sustained neuronal
      activity in mature networks and brain-derived neurotrophic factor each modulate
      the expression or function of KCC2. The resulting changes in intracellular
      chloride concentration alter the nature or strength of fast GABAergic
      neurotransmission, profoundly affecting the development and function of neuronal
      networks.

PMID- 17234401
TI  - Controlling the chromatin organization of vitamin D target genes by multiple
      vitamin D receptor binding sites.
AB  - An essential prerequisite for the direct modulation of transcription by 1alpha,25
      dihydroxy vitamin D(3) (1alpha,25(OH)(2)D(3)) is the location of at least one
      activated vitamin D receptor (VDR) protein close to the transcription start site
      of the respective primary 1alpha,25(OH)(2)D(3) target gene. This is achieved
      through the specific binding of VDR to a 1alpha,25(OH)(2)D(3) response element
      (VDRE). Although these elements are well characterized in vitro, the function of
      VDREs in living cells in the context of chromatin is still largely unknown. To
      resolve this issue, approximately 8kB of the promoter regions of the primary
      1alpha,25(OH)(2)D(3) target genes CYP24, cyclin C and p21((Waf1/Cip1)) were
      screened by chromatin immunoprecipitation (ChIP) assays for VDR binding sites
      using antibodies against VDR and its partner proteins. This approach identified
      three to four functional VDREs per gene promoter. In parallel, in silico
      screening of the extended gene areas (i.e. 10kB of promoter, introns, exons and
      10kB of the downstream region) of all six members of the insulin-like growth
      factor binding protein (IGFBP) gene family was performed. Gel shift, reporter
      gene and ChIP assays identified in total 10 functional VDREs in the genes IGFBP1,
      IGFBP3 and IGFBP5. Taken together, both screening approaches suggest that a
      reasonable proportion of all VDR target genes, if not all, are under the control
      of multiple VDREs.

PMID- 17234402
TI  - 13th Workshop consensus for vitamin D nutritional guidelines.

PMID- 17234403
TI  - Biosorption of lead and copper from aqueous solutions by pre-treated crab and
      arca shell biomass.
AB  - Sorption potential of pretreated crab and arca shell biomass for lead and copper
      from aqueous media was explored. The effects of pH, initial concentration,
      biosorbent dosage and contact time were studied in batch experiments. Effects of
      common ions like sodium, potassium, calcium and magnesium on the sorption
      capacity of pretreated crab and arca biomasses were also studied. At equilibrium,
      the maximum uptake by crab shell biomass was 19.83+/-0.29 and 38.62+/-1.27 mg/g
      for lead and copper, respectively. In case of arca shell biomass the maximum
      uptake capacity was 18.33+/-0.44 mg/g and 17.64+/-0.31 mg/g for lead and copper,
      respectively. Combined effect of all the common ions up to 50 microg/ml
      concentration was negligible for both the metals using both biomasses. Sorption
      isotherms were studied to explain the removal mechanism of both elements by
      fitting isotherms data into Lagergren, Freundlich and Langmuir equations.

PMID- 17234404
TI  - A novel method of single step hydrophobic interaction chromatography for the
      purification of phycocyanin from Phormidium fragile and its characterization for
      antioxidant property.
AB  - Phycocyanin--a major phycobiliprotein constitutively produced by many
      cyanobacteria--holds several promising applications in diagnostics, biomedical
      research, and therapeutics. This paper discusses a novel rapid method for the
      purification of cyanobacterial phycocyanin (C-PC) from Phormidium fragile using
      hydrophobic interaction chromatography. The protein was extracted and
      concentrated by grinding under liquid nitrogen and ammonium sulfate
      fractionation. C-PC was purified by single step hydrophobic interaction
      chromatography. Purified phycocyanin showed absorbance maximum (lambda(max)) at
      624 nm. The criterion of purity (R) achieved was 4.52. Phycocyanin to
      phycoerythrin and phycocyanin to allophycocyanin purity ratio were 3.85 and 7.49,
      respectively. The purified protein showed a pI of 5.2 and has two subunits with
      molecular mass of 19 and 20 kDa each, corresponding to its highly reported alpha
      and beta subunits. The subunits of phycocyanin were confirmed by their bilin
      fluorescence using zinc assisted fluorescence enhancement technique. Intact C-PC
      was of 125 kDa as determined by HPLC, suggested the (alphabeta)(3) subunit
      assembly. Results obtained by this method in terms of purity, recovery, process
      time, simplicity, and efficacy are much better than previous methodologies.
      Purified phycocyanin was further scrutinized for its antioxidant capacity and
      judged against five non-enzymatic antioxidants by FRAP assay.

PMID- 17234405
TI  - An evaluation of 3,4-methylenedioxy phenyl replacements in the aminopiperidine
      chromone class of MCHr1 antagonists.
AB  - The optimization of potent MCHr1 antagonist 1 with respect to improving its in
      vitro profile by replacement of the 3,4-methylenedioxy phenyl (piperonyl) moiety
      led to the discovery of 19, a compound that showed excellent MCHr1 binding and
      functional potencies in addition to possessing superior hERG separation, CYP3A4
      profile, and receptor cross-reactivity profiles.

PMID- 17234406
TI  - 1,3-diaminopropan-2-ol sulfonamides as potent and selective inhibitors of the
      glycine transporter type 1.
AB  - High throughput screening led to the discovery of a novel series of 1,3
      diaminopropan-2-ol sulfonamides as selective GlyT-1 inhibitors. Structure
      activity relationships of this novel series and optimisation of the initial hit
      that led to the identification of (2), a potent and selective GlyT-1 inhibitor,
      are also presented.

PMID- 17234407
TI  - The synthesis and structure-activity relationship studies of selective acetyl-CoA
      carboxylase inhibitors containing 4-(thiazol-5-yl)but-3-yn-2-amino motif: polar
      region modifications.
AB  - The structure-activity relationship study focused on the polar region of the HTS
      hit A-80040 (1) producing several series of potent and selective ACC2 inhibitors.
      The SAR suggests a compact lipophilic pocket that does not tolerate polar and
      ionic groups. Replacement of the hydroxyurea group with isoxazoles improves ACC2
      selectivity while maintaining potency. Variations at the propargylic site of 11a
      reduce ACC2 potency.

PMID- 17234408
TI  - A new visual screening assay for catalytic antibodies with retro-aldol retro
      Michael activity.
AB  - Fast and convenient methods are required for the detection of novel catalysts. We
      have developed a new assay to allow direct visualization of retro-aldol retro
      Michael catalytic activity and have demonstrated it with catalytic antibody 38C2.
      The assay is based on a catalytic cleavage of a physiologically stable substrate
      to release 3,4-cyclohexeneoesculetin. The latter then reacts with iron(III) to
      generate a non-soluble complex that precipitates in the form of a black dye. This
      assay may be used for screening new catalysts for retro-aldol retro-Michael
      activity with improved efficiency for specific prodrug activation.

PMID- 17234409
TI  - Butyl 2-(4-[1.1'-biphenyl]-4-yl-1H-imidazol-2-yl)ethylcarbamate, a potent sodium
      channel blocker for the treatment of neuropathic pain.
AB  - A series of 4-arylimidazole carbamates was synthesized and their binding
      affinities to the site-2 sodium (Na+) channel were determined. SAR studies led to
      the identification of compound 10, a potent Na+ channel blocker which was
      efficacious in pain models in vivo.

PMID- 17234410
TI  - Discovery of thienopyridines as Src-family selective Lck inhibitors.
AB  - We describe the identification, SAR, and in vivo pharmacology of a new series of
      Src-family selective Lck inhibitors. These thienopyridines were designed based on
      a desire to access the unique residues in the extended hinge region of Lck.

PMID- 17234411
TI  - HeLa cells apoptosis induced by 1,7-dimethyl-1,4,7,10-tetraazacyclododecane.
AB  - Preliminary pharmacological tests showed that 1,7-dimethyl-1,4,7,10
      tetraazacyclododecane (DMC) had antitumor activity against HeLa and A549 cell
      lines in vitro. The HeLa cells apoptosis induced by DMC was examined by flow
      cytometric meter, and further confirmed by observing the morphological changes
      and DNA fragmentation. No observation of A549 cells induced apoptosis was
      observed by DMC.

PMID- 17234412
TI  - Synthesis of 3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo[1,2-b]pyridine,
      a potent cyclin dependent kinase 1 (CDK1) inhibitor.
AB  - The novel compound 3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo[1,2
      b]pyridine was discovered to be a potent CDK1 inhibitor. Described here is the
      chemistry for its synthesis, including Pd(II) catalyzed Stille coupling reaction
      and sulfur(0) induced benzimidazole formation. Its effects on VEGFR-2 kinase
      activity and tumour cell proliferation are also described.

PMID- 17234413
TI  - Synthesis and QSAR studies on hypotensive 1-[3-(4-substituted phenylthio) propyl]
      4-(substituted phenyl) piperazines.
AB  - A series of 1-[3-(4-substituted phenylthio) propyl]-4-(substituted phenyl)
      piperazines has been synthesized and evaluated for hypotensive activity. The QSAR
      studies indicate that resonance and hydrophobic parameters of the aryl
      substituents are important for hypotensive activity. The similar role of
      resonance parameter in describing the variance of 5-HT(2A) receptor binding
      affinities of these compounds suggests a possible role of 5-HT(2A) receptors in
      mediating the hypotensive action of title compounds.

PMID- 17234414
TI  - 3H-[1,2,4]-Triazolo[5,1-i]purin-5-amine derivatives as adenosine A2A antagonists.
AB  - A novel series of 3-substituted-8-aryl-[1,2,4]-triazolo[5,1-i]purin-5-amine
      analogs related to Sch 58261 was synthesized in order to identify potent
      adenosine A(2A) receptor antagonists with improved selectivity over the A(1)
      receptor, physiochemical properties, and pharmacokinetic profiles as compared to
      those of Sch 58261. As a result of structural modifications, numerous analogs
      with excellent in vitro binding affinities and selectivities were identified.
      Moreover, compound 27 displayed both superior in vitro and highly promising in
      vivo profiles.

PMID- 17234415
TI  - Novel trifluoroacetophenone derivatives as malonyl-CoA decarboxylase inhibitors.
AB  - A series of trifluoroacetophenone derivatives were prepared and evaluated as
      malonyl-CoA decarboxylase (MCD) inhibitors. Some of the 'reverse amide' analogs
      were found to be potent inhibitors of MCD enzyme activity. The trifluoroacetyl
      group may interact with the MCD active site as the hydrate in a similar fashion
      to the hexafluoroisopropanol analogs reported previously. Adding electron
      withdrawing groups to the phenyl ring stabilizes the hydrated species and
      enhances this interaction.

PMID- 17234416
TI  - In vitro antimalarial activity of hyperforin, a prenylated acylphloroglucinol. A
      structure-activity study.
AB  - The antimalarial activity of hyperforin, a phenol-like compound that can be
      easily absorbed orally, and a series of derivatives variously modified on the
      cyclohexatrienone system was investigated. Hyperforin was active against
      Plasmodium falciparum with an IC(50) value in the micromolar range, and the
      activity was not critically dependent on either its phenol-like sensitivity to
      autooxidation or the presence of unsaturation on the prenyl residues. Related
      phloroglucinols like the hop beta-acids and the enantiomers of usnic acid showed
      only marginal activity, suggesting that hyperforin is a new antimalarial
      chemotype.

PMID- 17234417
TI  - Discovery of anticonvulsant activity of abietic acid through application of
      linear discriminant analysis.
AB  - Linear discriminant analysis was performed to derive discriminant functions based
      on 2D descriptors and capable of classifying anticonvulsant from non
      anticonvulsant compounds. Through application in virtual screening of the
      discriminant function which performed best in the validation steps, abietic acid
      was identified as a potential new anticonvulsant agent. The anticonvulsant
      activity of abietic acid at 30 and 100mg/kg was confirmed in the Maximal
      Electroshock Test, both orally and intraperitoneally.

PMID- 17234418
TI  - Relatives' experiences in intensive care--finding a place in a world of
      uncertainty.
AB  - The aim of the study was to explore and describe the experiences of relatives of
      critically ill patients in adult intensive care. A qualitative research design
      was chosen, using a Grounded Theory approach. In-depth interviews were conducted
      with four spouses and three parents in a Danish University Hospital. An overall
      process of fitting in was apparent, explaining how relatives tried to manoeuvre
      in a chaotic and scary situation. The relatives were clearly in turmoil, yet
      found ways of coping in the situation and developing adaptation ability. Three
      major strategies were identified: enduring uncertainty, putting self aside and
      forming personal cues. This explorative study points to relatives being
      vulnerable and resourceful at the same time, struggling to find a place,
      experiencing distance from the patient as well as from the professionals and
      uncertainty regarding what to expect and how to act in the ICU. The study is a
      contribution to understanding relatives' needs and strategies and to developing
      better communication and cooperation between nurses and the patients' relatives.

PMID- 17234419
TI  - Azetidinones as vasopressin V1a antagonists.
AB  - The azetidinone LY307174 (1) was identified as a screening lead for the
      vasopressin V1a receptor (IC50 45 nM at the human V1a receptor) based on
      molecular similarity to ketoconazole (2), a known antagonist of the luteinizing
      hormone releasing hormone receptor. Structure-activity relationships for the
      series were explored to optimize receptor affinity and pharmacokinetic
      properties, resulting in compounds with Ki values <1nM and brain levels after
      oral dosing approximately 100-fold higher than receptor affinities.

PMID- 17234420
TI  - HSP90-like artificial chaperone activity based on indole beta-cyclodextrin.
AB  - Indole beta-cyclodextrin (beta-1) was found to be able to prevent aggregation of
      citrate synthase (CS) on heating condition. As a result, beta-1 showed anti-CS
      aggregation in this system by regulating in early stage. The depression mechanism
      of beta-1 for aggregation of CS is as follows: the beta-1 formed a complex with
      hydrophobic parts of the beta-sheet structure of CS. From CD spectra, CS was
      changed own conformation was changed by beta-1 addition. So, it was concluded
      that beta-1 works as beta-sheet inducer in thermal condition. On the other hand,
      native beta-cyclodextrin (beta-CyD) shows small suppression capability for CS
      aggregation.

PMID- 17234421
TI  - Cell-penetrating autoantibody induces caspase-mediated apoptosis through
      catalytic hydrolysis of DNA.
AB  - In the present study, we investigated the substrate specificity of catalytic
      activity of a cytotoxic anti-DNA monoclonal autoantibody, G1-5, which was
      obtained from an MRL-lpr/lpr mouse by hybridoma technology. The antibody
      catalyzed hydrolysis of single- and double-stranded DNA with a higher substrate
      specificity for thymine than adenine by either beta-glycosidic or phosphodiester
      bond cleavage. The hydrolysis rate (kcat) showed maximum at acidic pH conditions,
      suggesting that the catalytic site of the antibody contains essential carboxylic
      group(s). Treatment of cells with the antibody promoted cell death and induced
      the activation of caspases. The cell death induced by the antibody was inhibited
      by the pan-caspase inhibitor. Furthermore, the antibody binds to cell membrane
      and penetrates into the cells. Our results suggest that the cell death is
      initiated by antibodies penetrating to cells and nucleus, hydrolyzing
      considerable amount of DNA, and mediating the caspase-dependent apoptotic
      pathway.

PMID- 17234422
TI  - Structure-activity relationships of novel piperazines as antagonists for the
      melanocortin-4 receptor.
AB  - During the investigation of antagonists for the MC4 receptor, we found that 10ab
      having a naphthyl group showed almost the same binding affinity for the MC4
      receptor as that of the lead compound 1 with a benzoyl group. We also developed a
      new type of compounds, namely, bis-piperazines, and found that the bis
      piperazines 10 exhibited a high affinity for the MC4 receptor. In particular, (-)
      10bg exhibited the highest affinity for the MC4 receptor with an IC50 value of
      8.13nM. In this paper, we present the design, synthesis, and structure-activity
      relationships of the novel bis-piperazines as MC4 receptor antagonists.

PMID- 17234423
TI  - A chronic treatment with CDP-choline improves functional recovery and increases
      neuronal plasticity after experimental stroke.
AB  - Chronic impairment of forelimb and digit movement is a common problem after
      stroke that is resistant to therapy. Although in the last years some studies have
      been performed to increase the efficacy of rehabilitative experience and
      training, the pharmacological approaches in this context remain poorly developed.
      We decided to study the effect of a chronic treatment with CDP-choline, a safe
      and well-tolerated drug that is known to stabilize membranes, on functional
      outcome and neuromorphological changes after stroke. To assess the functional
      recovery we have performed the staircase reaching test and the elevated body
      swing test (EBST), for studying sensorimotor integration and asymmetrical motor
      function respectively. The treatment with CDP-choline, initiated 24 h after the
      middle cerebral artery occlusion (MCAO) and maintained during 28 days, improved
      the functional outcome in both the staircase test (MCAO+CDP=87.0+/-6.6% pellets
      eaten vs. MCAO+SAL=40.0+/-4.5%; p<0.05) and the EBST (MCAO+CDP=70.0+/-6.8% vs.
      MCAO+SAL=88.0+/-5.4%; contralateral swing p<0.05). In addition, to study
      potential neuronal substrates of the improved function, we examined the dendritic
      morphology of layer V pyramidal cells in the undamaged motor cortex using a Golgi
      Cox procedure. The animals treated with CDP-choline showed enhanced dendritic
      complexity and spine density compared with saline group. Our results suggest that
      a chronic treatment with CDP-choline initiated 24 h after the insult is able to
      increase the neuronal plasticity within noninjured and functionally connected
      brain regions as well as to promote functional recovery.

PMID- 17234425
TI  - Comparison of three different chest drainages after coronary artery bypass
      surgery--a randomised trial in 150 patients.
AB  - OBJECTIVE: Drainage of blood from the mediastinum and pleura following open
      cardiac procedures is usually carried out using one or more large-bore plastic
      chest tubes. Recently small diameter siliastic drains have been reported to
      evacuate blood with a better patient comfort. The efficacy and safety of
      different chest tubes have not yet been fully evaluated. METHODS: One hundred
      fifty patients undergoing coronary artery bypass surgery were randomised to have
      either Blake) 24F (Ethicon, Inc, Somerville, NJ), Argyle 32F plastic (Tyco
      Healthcare, Tullamore, UK) or Jostra 32F silastic (Maquet Cardiopulmonary AG,
      Hirrlingen, Germany) drains inserted for evacuation of postoperative bleeding.
      Bleeding rate per hour, total blood loss, patient discomfort during drain
      removal, residual pleural fluid at chest X-ray 3 days and 3 weeks after the
      operation were recorded. RESULTS: Bleeding pattern and total bleeding did not
      differ significantly in the three groups. Median blood loss was 615 ml (quartile
      range 390-820 ml) in the Blake-group, 750 ml (quartile range 430-870 ml) in the
      Jostra-group and 580 ml (quartile range 450-750 ml) in the Argyle-group,
      respectively (p=0.17). Pain at removal the day after the operation was similar in
      the three groups. Residual fluid in the left pleura did not differ significantly
      at 3 days (p=0.41) or at 3 weeks postoperatively (p=0.42). CONCLUSIONS: None of
      the three chest tubes was superior to drain postoperative bleeding or considering
      pain at removal. Local clinical routines and cost aspects should be the guide in
      choosing drainage system for open cardiac operations.

PMID- 17234426
TI  - Protochlorophyll complexes with similar steady-state fluorescence characteristics
      can differ in fluorescence lifetimes. A model study in Triton X-100.
AB  - The steady-state and time-resolved fluorescence characteristics of
      protochlorophyll (Pchl) dissolved in neat Triton X-100 and in Triton X-100
      micelles were investigated, and the fluorescence lifetimes of different Pchl
      spectral forms were studied. Varying the concentration of Pchl or diluting the
      micellar solutions either with a buffer or with a micellar solution, 631-634, 645
      655, 680-692 and above 700 nm emitting Pchl complexes were prepared, the ratios
      of which varied from one another. The fluorescence decay of the 631-634 nm
      emitting (monomeric) form had a mono-exponential character with a 5.4-ns
      fluorescence lifetime. The long-wavelength Pchl complexes (aggregates) had two
      fluorescence lifetime values within a range of 1.4-3.9 ns and 0.15-0.84 ns, which
      showed high variability in different environments. Depending on the conditions,
      either mono- or double-exponential fluorescence decay was found for a
      fluorescence band at 680-685 nm. These data show that despite their very similar
      steady-state fluorescence properties, Pchl complexes can differ in fluorescence
      lifetimes, which may reflect different molecular structures, intrinsic geometries
      or different molecular interactions. This underlines the importance of complex
      spectroscopic analysis for a precise description of native and artificial
      chlorophyllous pigment forms.

PMID- 17234424
TI  - TNF-alpha knockout and minocycline treatment attenuates blood-brain barrier
      leakage in MPTP-treated mice.
AB  - Following intraparenchymal injection of the dopamine (DA) neurotoxin 6
      hydroxydopamine, we previously demonstrated passage of fluoresceinisothiocyanate
      labeled albumin (FITC-LA) from blood into the substantia nigra (SN) and striatum
      suggesting damage to the blood-brain barrier (BBB). The factors contributing to
      the BBB leakage could have included neuroinflammation, loss of DA neuron control
      of barrier function, or a combination of both. In order to determine which
      factor(s) was responsible, we assessed BBB integrity using the FITC-LA technique
      in wild-type (WT), tumor necrosis factor alpha (TNF-alpha) knockout (KO), and
      minocycline (an inhibitor of microglia activation) treated mice 72 h following
      treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Compared with
      WT mice, TNF-alpha KO mice treated with MPTP showed reduced FITC-LA leakage,
      decreased numbers of activated microglia, and reduced proinflammatory cytokines
      (TNF-alpha and interleukin 1beta) associated with significant MPTP-induced DA
      neuron loss. In contrast, minocycline treated animals did not exhibit significant
      MPTP-induced DA neuron loss although their FITC-LA leakage, numbers of activated
      microglia, and MPTP-induced cytokines were markedly attenuated. Since both TNF
      alpha KO and minocycline treatment attenuated MPTP-induced BBB dysfunction,
      microglial activation, and cytokine increases, but had differential effects on DA
      neuron loss, it appears that neuroinflammation and not DA neuron loss was
      responsible for disrupting the blood-brain barrier integrity.

PMID- 17234428
TI  - Monitoring the degradation of tetracycline by ozone in aqueous medium via
      atmospheric pressure ionization mass spectrometry.
AB  - The degradation of tetracycline (1) by ozone in aqueous solution was
      investigated. High performance liquid chromatography (HPLC), UV-visible
      spectroscopy (UV-Vis), and total organic carbon (TOC) analyses revealed that
      although tetracycline was quickly consumed under this oxidative condition, it did
      not mineralize at all. Continuous monitoring by electrospray ionization mass
      spectrometry in the positive ion mode, ESI(+)-MS, revealed that tetracycline (1),
      detected in its protonated form ([1 + H]+) of m/z 445, reacted to yield almost
      exclusively two unprecedented oxidation products (2 and 3) via a net insertion of
      one and two oxygen atoms, respectively. Compound 2, suggested to be formed via an
      initial 1,3-dipolar cycloaddition of ozone at the C11a-C12 double-bond of 1, and
      Compound 3, proposed to be produced via a subsequent ozone attack at the C2-C3
      double-bond of 2, were detected in their protonated forms in the ESI(+)-MS, i.e.,
      [2 + H]+ of m/z 461 and [3 + H]+ of m/z 477, and were further characterized by
      ESI(+)-MS(n). LC-APCI(+)-MS (liquid chromatography coupled with atmospheric
      pressure chemical ionization mass spectrometry in the positive ion mode)
      experiments corroborated the results.

PMID- 17234427
TI  - Human leukocyte antigen and interleukin 2, 10 and 12p40 cytokine responses to
      measles: is there evidence of the HLA effect?
AB  - HLA class I and class II associations were examined in relation to measles virus
      specific cytokine responses in 339 healthy children who had received two doses of
      live attenuated measles vaccine. Multivariate linear regression modeling analysis
      revealed suggestions of associations between the expression of DPA1*0201 (p=0.03)
      and DPA1*0202 (p=0.09) alleles and interleukin-2 (IL-2) cytokine production
      (global p-value 0.06). Importantly, cytokine production and DQB1 allele
      associations (global p-value 0.04) revealed that the alleles with the strongest
      association with IL-10 secretion were DQB1*0302 (p=0.02), DQB1*0303 (p=0.07) and
      DQB1*0502 (p=0.06). Measles-specific IL-10 secretion associations approached
      significance with DRB1 and DQA1 loci (both global p-values 0.08). Specifically,
      suggestive associations were found between DRB1*0701 (p=0.07), DRB1*1103
      (p=0.06), DRB1*1302 (p=0.08), DRB1*1303 (p=0.06), DQA1*0101 (p=0.08), and
      DQA1*0201 (p=0.04) alleles and measles-induced IL-10 secretion. Further,
      suggestive association was observed between specific DQA1*0505 (p=0.002) alleles
      and measles-specific IL-12p40 secretion (global p-value 0.09) indicating that
      cytokine responses to measles antigens are predominantly influenced by HLA class
      II genes. We found no associations between any of the alleles of HLA A, B, and Cw
      loci and cytokine secretion. These novel findings suggest that HLA class II genes
      may influence the level of cytokine production in the adaptive immune responses
      to measles vaccine.

PMID- 17234429
TI  - Cyclization reaction of peptide fragment ions during multistage collisionally
      activated decomposition: an inducement to lose internal amino-acid residues.
AB  - During characterization of some peptides (linear precursors of the cyclic
      peptides showing potential to be anticancer drugs) in an ion trap, it was noted
      that many internal amino acid residues could be lost from singly charged b ions.
      The phenomenon was not obvious at the first stage of collisionally activated
      decomposition (CAD), but was apparent at multiple stages of CAD. The unique
      fragmentation consisting of multiple steps is induced by a cyclization reaction
      of b ions, the mechanism of which has been probed by experiments of N
      acetylation, MS(n), rearranged-ion design, and activation-time adjustment. The
      fragmentation of synthetic cyclic peptides demonstrates that a cyclic peptide
      intermediate (CPI) formed by b ion cyclization exhibits the same fragmentation
      pattern as a protonated cyclic peptide. Although no rules for the cyclization
      reaction were discerned in the experiments of peptide modification, the
      fragmentations of a number of b ions indicate that the "Pro and Asn/Gln effects"
      can influence ring openings of CPIs. In addition, large-scale losses of internal
      residues from different positions of a-type ions have been observed when pure
      helium was used as collision gas. The fragmentation is initiated by a cyclization
      reaction forming an a-type ion CPI. This CPI with a fixed-charge structure cannot
      be influenced by the "Pro effect", causing a selective ring opening at the amide
      bond Pro-Xxx rather than Xxx-Pro. With the knowledge of the unique fragmentations
      leading to internal residue losses, the misidentification of fragments and
      sequences of peptides may be avoided.

PMID- 17234430
TI  - Expression profile of receptors for myelin-associated inhibitors of axonal
      regeneration in the intact and injured mouse central nervous system.
AB  - Although CNS neurons have the potential to regenerate their axons after injury,
      myelin debris carrying axon growth inhibitors rapidly induce growth cone
      collapse. Receptors (NgR1, NgR2) and coreceptors (LINGO-1, p75(NTR), TROY) for
      these inhibitors have been characterized and transduction pathways partially
      identified. However, little is known about the expression of these receptors in
      intact and lesioned supraspinal projection neurons. Using in situ hybridization,
      immunohistochemistry and neuronal tract-tracing, we found that NgR1, NgR2 and
      LINGO-1 are strongly expressed in several neuronal populations of the adult mouse
      brain projecting to the spinal cord, including neurons projecting through the
      corticospinal, rubrospinal, caerulospinal, reticulospinal, raphespinal and
      vestibulospinal tracts. As expected, p75(NTR) expression was restricted to
      neuronal descending pathways from the brainstem. TROY was absent from most brain
      regions and from all neuronal projection systems, suggesting that additional
      signal-transducing coreceptors exist. Qualitative and quantitative analyses
      revealed that brain expression for these receptors was not affected by a severe
      T10 spinal cord contusion.

PMID- 17234432
TI  - Immunoglobulin heavy chain constant region of five Acipenseridae: cDNA sequence
      and evolutionary relationship.
AB  - The immunoglobulin M (IgM) heavy chain constant region genes of Russian sturgeon
      (Acipenser gueldenstaedtii), Sterlte sturgeon (Acipenser ruthenus), Amur sturgeon
      (Acipenser schrenckii), Chinese sturgeon (Acipenser sinensis) and Great sturgeon
      (Huso huso) were cloned and analyzed with molecular biology and bioinformatics
      methods. We cloned IGH nucleic acid sequences by RT-PCR using the specific
      primer, then determined the characteristics and functions of the amino acid
      sequences. The gene contains four constant region domain-encoding exons (CH1-4),
      of which CH4 sub-regions were the most conserved in IgM heavy chain constant
      region domain and had the highest identity within all the experimental species.
      According to the analysis of the phylogenetic tree, the variation expectation
      value (K(aa)), and species differentiation time (T) in the CH4 sub-region, we
      found that Chinese sturgeon and the other five sturgeon form one whole
      bifurcation of the tree, while, among the five left, Amur sturgeon and Huso
      sturgeon, Russian sturgeon and Siberian sturgeon (data from GenBank), Sterlte
      itself forms three other bifurcations. This result can clearly explain the
      relations of taxonomic status, geographical distribution and evolution among the
      species studied.

PMID- 17234431
TI  - Rho GTPases regulate PTPmu-mediated nasal neurite outgrowth and temporal
      repulsion of retinal ganglion cell neurons.
AB  - Members of the receptor protein tyrosine phosphatase (RPTP) subfamily of cell
      adhesion molecules (CAMs) mediate neurite outgrowth and growth cone repulsion.
      PTPmu is a growth permissive substrate for nasal retinal ganglion cell (RGC)
      neurites and a growth inhibitory substrate for temporal RGCs. In this manuscript,
      we demonstrate that the distinct PTPmu-dependent phenotypes of nasal outgrowth
      and temporal repulsion are regulated by Rho GTPases. The role of Rho GTPases in
      the regulation of nasal outgrowth and temporal repulsion was tested by utilizing
      dominant negative and constitutively active forms of Rac1, RhoA and Cdc42 in
      Bonhoeffer stripe assays. Nasal neurite outgrowth on PTPmu was blocked by Cdc42
      DN. Temporal repulsion to a PTPmu substrate was substantially reduced by addition
      of Cdc42-DN. The molecule that regulates the switch between permissive versus
      repulsive responses to PTPmu is Rac1 for temporal neurons. Inhibition of Rac1 is
      required for repulsion of temporal neurons. Interestingly, adding Rac1-CA to
      temporal RGC neurons converted PTPmu-dependent repulsion to a permissive
      response. In addition, adding exogenous Rac1-DN to nasal neurons induced a
      phenotype switch from a permissive to repulsive response to PTPmu. Together these
      data suggest that Cdc42 activity is required for both permissive and repulsive
      responses to PTPmu. However, the key to PTPmu-dependent repulsion is inhibition
      of Rac1 activity in temporal RGC neurons.

PMID- 17234433
TI  - Experience-dependent formation of activity propagation patterns at the
      somatosensory S1 and S2 boundary in rat cortical slices.
AB  - Somatosensory information is serially processed by the primary (S1) and secondary
      (S2) cortices, which can be identified in fresh cortical slices. We visualized
      activity propagation between S1 and S2 in rat cortical slices using flavoprotein
      fluorescence imaging. When S1 was stimulated, fluorescence responses extended
      into S2, while responses hardly propagated to S1 following S2 stimulation. The
      dominant activity propagation pattern from S1 to S2 was not affected by
      antagonists of glutamate or GABA(A) receptors. Ca(2+) imaging and
      electrophysiological recordings confirmed the anisotropic activity propagation
      pattern. This pattern could be formed as a result of serial information
      processing in S1 and S2. To test this hypothesis, activity propagation was
      investigated in cortical slices prepared 2 weeks or 3 days after trimming
      contralateral whiskers that provide massive inputs to S1. Supragranular
      activities in the barrel cortex were clearly suppressed. Furthermore, activities
      elicited in the rostral small vibrissae/mouth area of S1 near the border between
      S1 and S2 spread into the adjacent barrel cortex rather than into S2. Behavioral
      effects of whisker trimming were evaluated using a test, in which rats chose one
      of two bridges that had a wall on the right or left side only. Immediately after
      hemilateral whisker trimming, rats preferred to use the bridge with a wall close
      to the intact side. However, this preference disappeared 3 days after trimming.
      Modified activities observed in cortical slices after whisker trimming might be
      mechanisms for this behavioral compensation. These findings suggest experience
      dependent formation of activity propagation patterns in the somatosensory cortex.

PMID- 17234435
TI  - Modelling the role of excitatory and inhibitory neuronal activity in the
      generation of the BOLD signal.
AB  - A biophysical model of the coupling between neuronal activity and the BOLD signal
      that allows for explicitly evaluating the role of both excitatory and inhibitory
      activity is formulated in this paper. The model is based on several physiological
      assumptions. Firstly, in addition to glycolysis, the "glycogen shunt" is assumed
      for excitatory synapses as a mechanism for energy production in the astrocytes.
      As a result, oxygen-to-glucose index (OGI) is not constant but varies with
      excitatory neuronal activity. In contrast, a constant OGI=6 (glycolysis) is
      assumed for inhibitory synapses. Finally we assume that cerebral blood flow is
      not directly controlled by energy usage, but it is only related to excitatory
      activity. Simulations' results show that increases in excitatory activity amplify
      the oscillations associated with the transient BOLD response, by increasing the
      initial dip, the maximum, and the post-stimulus undershoot of the signal. In
      contrast, increasing the inhibitory activity evoked an overall decrease of the
      BOLD signal along the whole time interval of the response. Simultaneous increase
      of both types of activity is then expected to reinforce the initial dip and the
      post-stimulus undershoot, while respective effects on the maximum tend to
      counteract each other. Two mechanisms for negative BOLD response (NBS) generation
      were predicted by the model: (i) when inhibition was present alone or together
      with low activation levels and (ii) when deactivation occurred independently of
      the accompanying inhibition level. Interestingly, NBS was associated with
      negative oxygen consumption changes only for the case of mechanism (ii).

PMID- 17234434
TI  - Somatosensory dynamic gamma-band synchrony: a neural code of sensorimotor
      dexterity.
AB  - To investigate neural coding characteristics in the human primary somatosensory
      cortex, two fingers with different levels of functional skill were studied. Their
      dexterity was scored by the Fingertip writing test. Each finger was separately
      provided by a passive simple sensory stimulation and the responsiveness of each
      finger cortical representation was studied by a novel source extraction method
      applied to magnetoencephalographic signals recorded in a 14 healthy right handed
      subject cohort. In the two hemispheres, neural oscillatory activity
      synchronization was analysed in the three characteristic alpha, beta and gamma
      frequency bands by two dynamic measures, one isolating the phase locking between
      neural network components, the other reflecting the total number of synchronous
      recruited neurons. In the dominant hemisphere, the gamma band phase locking was
      higher for the thumb than for the little finger and it correlated with the contra
      lateral finger dexterity. Neither in the dominant nor in the non-dominant
      hemisphere, any effect was observed in the alpha and beta bands. In the gamma
      band, the amplitude showed similar tendency to the phase locking, without
      reaching statistical significance. These findings suggest the dynamic gamma band
      phase locking as a code for finger dexterity, in addition to the magnification of
      somatotopic central maps.

PMID- 17234436
TI  - Simultaneous changes of leg circumference and interface pressure under different
      compression bandages.
AB  - OBJECTIVES: To assess the validity of measuring changes of sub bandage pressure
      and leg circumference in different body positions for an in vivo characterization
      of the elastic properties of bandage systems. DESIGN: Experimental study.
      MATERIALS AND METHODS: Different compression bandages were applied on the leg.
      The variations of interface pressure and leg circumference above the inner ankle
      (that depends on the elastic property of the bandage) were measured
      simultaneously by a pressure transducer and by strain-gauge plethysmography in 50
      patients. Stiffness is defined as the increase of pressure per increase of
      circumference. RESULTS: The most consistent parameter to differentiate elastic
      from inelastic bandages was the pressure-difference between the standing and the
      lying position corrected for the actual increase of leg circumference (modified
      static stiffness index, mSSI; sensitivity and specificity 100%). Neglecting the
      individual changes of the circumference and considering the pressure difference
      alone allows a differentiation which is slightly less accurate (sensitivity 100%,
      specificity 88%) but much simpler to use. CONCLUSIONS: The static stiffness index
      is a useful tool to differentiate elastic from inelastic bandage material even
      without correction for the individual increase of leg circumference.

PMID- 17234437
TI  - Caries-related saliva properties in individuals with 22q11 deletion syndrome.
AB  - OBJECTIVES: The aims were to compare saliva secretion rate, buffer capacity,
      cariogenic bacteria, total protein, IgA, and electrolytes between patients with
      22q11 deletion syndrome (22q11DS) and control subjects and to study correlations
      between saliva and serum levels of IgA and electrolytes in 22q11DS patients.
      STUDY DESIGN: Twenty-nine consecutive 22q11DS patients (mean age 12.6 years) and
      matched healthy control subjects were clinically examined, and stimulated saliva
      samples were collected. RESULTS: Patients with 22q11DS had impaired salivary
      secretion rate (P < .01) and buffer capacity (P < .05), higher numbers of
      cariogenic bacteria (P < .01), increased saliva protein concentrations (P <
      .001), and reduced output of electrolytes (P < .001-.05) compared with control
      subjects. A correlation between concentration in serum and saliva was found only
      for IgA (r = .622; P < .01). CONCLUSIONS: Different salivary components were
      affected in patients with 22q11DS, which may explain the increased caries risk
      seen in these patients.

PMID- 17234438
TI  - Inherited metabolic disease in companion animals: prospects for their diagnosis
      and elimination in the next decade.

PMID- 17234439
TI  - Mechanisms of adrenosensitivity in capsaicin induced hyperalgesia.
AB  - It is well known that iontophoresis of norepinephrine in capsaicin treated skin
      is followed by an increase in thermal hyperalgesia. It is unclear if this action
      on nocicepitive afferents involves the release of prostaglandins. The aim of the
      present study was to determine: (1) the effect of norepinephrine iontophoresis on
      spontaneous and evoked pain in the human skin after topical application of
      capsaicin; (2) the effect of cyclooxygenase (COX) inhibition on changes in pain
      perception induced by norepinephrine application. METHODS: Ten volunteers were
      included in the study. Iontophoresis of norepinephrine or saline was performed in
      a randomized cross over design on the volar aspect of the forearm after topical
      application of capsaicin. In the second part of the study single iv. injections
      of saline or acetylsalicylic acid were performed in a randomized double blind
      cross over design. After the injection norepinephrine iontophoresis was performed
      on the skin treated with topical capsaicin. Spontaneous pain, mechanical
      hyperalgesia as well as warm and heat pain thresholds were measured before and
      after each iontophoresis. RESULTS: Norepinephrine did enhance spontaneous pain
      and mechanical and thermal hyperalgesia in capsaicin treated skin. Inhibition of
      COX I and II had no effect on the norepinephrine induced changes in pain
      perception. CONCLUSION: The results do not support the assumption that in human
      skin sensitized by topical capsaicin application of norepinephrine acts on
      nociceptive afferents via the release of prostaglandins. Thus, a direct action of
      norepinephrine on adrenergic receptors in the membrane of the afferent fibers is
      most likely.

PMID- 17234440
TI  - Allometry of thermal limitation in the cephalopod Sepia officinalis.
AB  - Cuttlefish (Sepia officinalis) routine metabolic rate was determined in response
      to acute thermal changes at a rate of 1 degrees C h(-1) for a variety of animal
      sizes (15-496 g wet mass, laboratory reared at 15 degrees C). In a thermal frame
      of 11 to 23 degrees C, oxygen consumption rates (MO(2), in mumol O(2) g(-1) min(
      1)) were observed to rise with increasing temperature (T, in degrees C) and to
      decline with increasing body mass (m, in g), according to the formula: ln MO(2)=
      3.3+0.0945T-0.215 ln m (R(2)=0.93). Outside the above thermal window, animals
      were not able to increase MO(2) at similar rates, indicating a beginning oxygen
      limitation of metabolism. Large animals (>100 g body mass) already displayed
      lower than expected MO(2) values at 8 and 26 degrees C, while smaller animals (15
      g wet mass) were characterized by a wider thermal window (MO(2) values deviated
      from expected rates at 5 and 29 degrees C). Morphometric data of cuttlefish
      mantle skin area was obtained to discuss size - related effects of skin
      respiration potential on thermal tolerance. Cuttlefish growth was observed to be
      isometric, as constant 'Vogel numbers' of 4.2 indicated (animal body masses: 11
      to 401 g). In the same mass range, specific mantle surface area declined three
      fold from 10.7 (0.24) (means+/-SD) to 3.3 (0.52) cm(2) g(-1). Thus, increased
      thermal tolerance in smaller animals may be enabled by a higher skin respiration
      potential due to higher specific skin surface areas. An elevated fraction of
      MO(2) provided by means of skin respiration in small animals could relieve the
      cardiovascular system, which previously has been found a major limiting component
      during acute thermal stress in cuttlefish.

PMID- 17234441
TI  - Determination of the anaerobic threshold and maximal lactate steady state speed
      in equines using the lactate minimum speed protocol.
AB  - Maximal blood lactate steady state concentration (MLSS) and anaerobic threshold
      (AT) have been shown to accurately predict long distance events performance and
      training loads, as well, in human athletes. Horse endurance races can take up to
      160 km and, in practice, coaches use the 4 mM blood lactate concentration, a
      human based fixed concentration to establish AT, to predict training loads to
      horse athletes, what can lead to misleading training loads. The lactate minimum
      speed (LMS) protocol that consists in an initial elevation in blood lactate level
      by a high intensity bout of exercise and then establishes an individual
      equilibrium between lactate production and catabolism during progressive
      submaximal efforts, has been proposed as a nonfixed lactate concentration, to
      measure individual AT and at the same time predicts MLSS for human long distance
      runners and basketball players as well. The purpose of this study was to
      determine the reliability of the LMS protocol in endurance horse athletes. Five
      male horses that were engaged on endurance training, for at least 1 year of
      regular training and competition, were used in this study. Animals were submitted
      to a 500 m full gallop to determine each blood lactate time to peak (LP) after
      these determinations, animals were submitted to a progressive 1000 m exercise,
      starting at 15 km h(-1) to determine LMS, and after LMS determination animals
      were also submitted to two 10,000 m running, first at LMS and then 10% above LMS
      to test MLSS accuracy. Mean LP was 8.2+/-0.7 mM at approximately 5.8+/-6.09 min,
      mean LMS was 20.75+/-2.06 km h(-1) and mean heart rate at LMS was 124.8+/-4.7
      BPM. Blood lactate remained at rest baseline levels during 10,000 m trial at LMS,
      but reached a six fold significantly raise during 10% above LMS trial after 4000
      and 6000 m (p<0.05) and (p<0.01) after 8000 and 10,000 m. In conclusion, our
      adapted LMS protocol for horse athletes proposed here seems to be a reliable
      method to state endurance horse athletes LT and MLSS.

PMID- 17234443
TI  - REMOVED: Short-chain acyl-CoA dehydrogenase gene mutation (319 C>T) presents with
      clinical heterogeneity and is candidate founder mutation in Ashkenazi Jewish
      population.
AB  - This article has been removed, consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 17234442
TI  - Physiological basis for diurnal activity in dispersing juvenile Bufo granulosus
      in the Caatinga, a Brazilian semi-arid environment.
AB  - Diurnal activity is characteristic of many toad species, including Bufo
      granulosus from the Brazilian semi-arid biome called the Caatinga. Because of
      their patterns of activity, juvenile toads are exposed to hot and dehydrating
      conditions. Our investigation focuses on temperature and water relationships, and
      is based on the prediction that anuran diurnal activity in a semi-arid
      environment must be associated with morphological, physiological and behavioral
      traits enhancing thermal tolerances, capacity for performance at high
      temperatures and water balance. To test specific hypothesis related with this
      prediction, we investigated postmetamorphic B. granulosus and collected data on
      thermal tolerances and preferences, thermal safety margins, thermal dependence of
      locomotor behavior, thermal and kinetic properties of citrate synthase (CS), and
      skin morphophysiology. This information was compared with additional data from
      adult conspecifics and adult toads from sympatric species or from species from
      more moderate environments. We found that juvenile B. granulosus exhibit the
      highest critical maximum temperature reported for toads (44.2 degrees C) and are
      well suited to move at high temperatures. However, and in contrast with juveniles
      of other Bufo species, they do not show thermal preferences in a gradient and
      appear to hydroregulate more than thermoregulate. The CS of adult and juvenile
      toads shows typical patterns of thermal sensibility, but the thermal stability of
      this enzyme is much higher in juveniles than in adult Bufo of any other species
      studied. The inguinal skin exhibits a complex folding pattern and seems highly
      specialized for capillary water uptake. Diurnal activity in juvenile B.
      granulosus is possible given high thermal tolerances, keen ability to detect and
      uptake water, and avoidance behaviors.

PMID- 17234444
TI  - Bubbles in an acoustic field: an overview.
AB  - Acoustic cavitation is the fundamental process responsible for the initiation of
      most of the sonochemical reactions in liquids. Acoustic cavitation originates
      from the interaction between sound waves and bubbles. In an acoustic field,
      bubbles can undergo growth by rectified diffusion, bubble-bubble coalescence,
      bubble dissolution or bubble collapse leading to the generation of primary
      radicals and other secondary chemical reactions. Surface active solutes have been
      used in association with a number of experimental techniques in order to isolate
      and understand these activities. A strobe technique has been used for monitoring
      the growth of a single bubble by rectified diffusion. Multibubble
      sonoluminescence has been used for monitoring the growth of the bubbles as well
      as coalescence between bubbles. The extent of bubble coalescence has also been
      monitored using a newly developed capillary technique. An overview of the various
      experimental results has been presented in order to highlight the complexities
      involved in acoustic cavitation processes, which on the other hand arise from a
      simple, mechanical interaction between sound waves and bubbles.

PMID- 17234445
TI  - Rac signaling in tumorigenesis and as target for anticancer drug development.
AB  - Rac GTPases are crucial signaling regulators in eukaryotic cells, acting
      downstream of many cell surface receptors. They play essential roles in diverse
      cellular functions including cytoskeleton dynamics, cell motility, cell survival
      and apoptosis. Their activities are controlled by a tightly regulated GDP/GTP
      cycle coupled with an alternation between cytoplasm and membrane compartments.
      Aberrant Rac signaling is found in some human cancers as a result of changes in
      the GTPase itself or in its regulation loops. This review highlights recent
      findings regarding the molecular and functional aspects of Rac that mediate
      tumorigenic transformation and metastasis. It also describes the cellular
      mechanisms that potentially explain the complex role of Rac in tumorigenesis.
      Finally, it discusses approaches for modulating Rac function as a potential
      anticancer strategy.

PMID- 17234446
TI  - Pore-forming toxins and cellular non-immune defenses (CNIDs).
AB  - Pore-forming toxins (PFTs) are the most common class of bacterial protein toxin
      and are important for bacterial pathogenesis. Recent studies have shown that the
      previous model stating that epithelial cells lyse in response to these toxins and
      have no defenses against these pores is oversimplified. Rather, it appears that
      cells have sophisticated mechanisms and signal-transduction pathways with which
      to respond to such an attack. There is a growing body of knowledge about how
      cells respond to and protect themselves against PFTs; this protection against
      PFTs is likely to be important in host survival to attack by bacterial pathogens,
      but does not neatly fit into current concepts of adaptive or innate immunity.
      Therefore, it is proposed that the terminology cellular non-immune defenses
      (CNIDs) be used to describe defenses that are employed by non-immune cells to
      protect against bacterial attack.

PMID- 17234447
TI  - The status of Quadriacanthus Paperna, 1961 and Anacornuatus Dubey et al., 1991
      (Monogenoidea: Dactylogyridae) with redescription of Q. kobiensis Ha Ky, 1968,
      new geographical records for Q. bagrae Paperna, 1979 and Q. clariadis Paperna,
      1961 from India and a note on speciation in Monogenoidea.
AB  - Quadriacanthus Paperna, 1961 is revised and emended. Q. kobiensis Ha Ky, 1968 is
      redescribed from Clarias batrachus, and Q. bagrae Paperna, 1979 and Q. clariadis
      Paperna, 1961 are recorded from C. gariepinus, both from the River Gomti,
      Lucknow. India is a new geographical record for Q. bagrae and Q. clariadis.
      Anacornuatus Dubey et al., 1991 is considered a junior subjective synonym of
      Quadriacanthus Paperna, 1961. Quadriacanthus spp. are more specific to their
      hosts (micro-habitats) than geographical localizations (macro-habitats)
      suggesting geographical diversification of hosts plays a lesser role in
      monogenoidean speciation.

PMID- 17234448
TI  - Modulation of apoptotic signalling by 9-hydroxystearic acid in osteosarcoma
      cells.
AB  - 9-hydroxystearic acid (9-HSA) belongs to the class of endogenous lipid
      peroxidation by-products that greatly diminish in tumors, causing as a
      consequence the loss of one of the control mechanisms on cell division. We have
      previously shown that 9-HSA controls cell growth and differentiation by
      inhibiting histone deacetylase 1 (HDAC1) activity. In this paper our attention
      has not only been focused on HDAC1 inhibition but also on the hyperacetylation of
      other substrates such as p53, that is involved in inducing cell cycle arrest
      and/or apoptosis, and whose activity and stability are known to be regulated by
      posttranslational modifications, particularly by acetylation at the C-terminus
      region. 9-HSA administration to U2OS, an osteosarcoma cell line p53 wt, induces a
      growth arrest of the cells in G2/M and apoptosis via a mitochondrial pathway. In
      particular hyperacetylation of p53 induced by the HDAC1 inhibitory activity of 9
      HSA has been demonstrated to increase Bax synthesis both at the transcriptional
      and the translational level. The subsequent translocation of Bax to the
      mitochondria is associated to a significant increase in caspase 9 activity. Our
      data demonstrate that the effects of 9-HSA on U2OS correlate with
      posttranslational modifications of p53.

PMID- 17234449
TI  - LSDP5 is a PAT protein specifically expressed in fatty acid oxidizing tissues.
AB  - The PAT family (originally named for Perilipin, ADFP and TIP47) now includes four
      members: Perilipins, ADFP, TIP47 and S3-12. Significant primary sequence homology
      and the ability to associate with lipid storage droplets (LSDs) are well
      conserved within this family and across species. In this study, we have
      characterized a novel PAT protein, lipid storage droplet protein 5 (LSDP5) of 463
      residues. A detailed sequence analysis of all murine PAT proteins reveals that
      LSDP5, TIP47 and ADFP share the highest order of sequence similarity, whereas
      perilipin and S3-12 have more divergent carboxyl- and amino-termini,
      respectively. Ectopically-expressed YFP-LSDP5 or flag-LSDP5 fusion proteins
      associate with LSDs. In accord with recent published data for perilipin, forced
      expression of LSDP5 in CHO cells inhibits lipolysis of intracellular LSDs. The
      LSDP5 gene is primarily transcribed in cells that actively oxidize fatty acids,
      such as heart, red muscle and liver. Expression of LSDP5 is stimulated by ligand
      activation of peroxisomal proliferator-activated receptor alpha (PPARalpha), and
      significantly reduced in liver and heart in the absence of this transcription
      factor. PPARalpha is generally required for regulation of fatty acid metabolism
      during fasting, but fasting induces LSDP5 mRNA in liver even in the absence of
      PPARalpha.

PMID- 17234450
TI  - The influence of different definition criteria on the PLM index.
AB  - BACKGROUND: Different criteria for the scoring of periodic leg movements (PLM)
      have been recently proposed. We investigated to what extent changes in PLM
      criteria for leg movement duration, intermovement interval and combination of
      bilateral leg movements (LM) influence the PLM index. METHODS: The nocturnal
      polysomnographies of 40 consecutive patients (20 males, 20 females, mean age 52+/
      16 years) with sleep-wake complaints but without severe sleep-related breathing
      disorders (AHI<20) were evaluated. All patients showed a minimum of 100 LMs
      during the night. For each night eight PLM indices during sleep (PLMS) and eight
      PLM indices during wakefulness (PLMW) were computed by systematically varying the
      following criteria: LM duration (0.5-5s vs. 0.5-10s), intermovement interval (5
      90s vs. 10-90s), and separation criteria for LMs occurring in both legs (<5s
      onset to onset vs. <0.5s offset to onset). Data were analyzed using linear mixed
      models. RESULTS: The two different intermovement intervals and the leg movement
      durations both had a statistically significant influence on the PLMS and PLMN
      indices. These variations were highly systematic but numerically small for the
      PLMS index while they were substantially larger for the PLMW index. The
      separation criteria or possible two-way interactions between the criteria had no
      influence on the PLM indices. CONCLUSIONS: Different criteria had a negligible
      influence on the PLM index during sleep. Across-study or sleep-laboratory
      comparability can be assumed within our parameter set. This does not apply to the
      PLM index during wakefulness.

PMID- 17234451
TI  - Immune responses to borrelial VlsE IR6 peptide variants.
AB  - Laboratory confirmation of Lyme borreliosis (LB) relies mainly on the
      demonstration of anti-borrelial antibodies. In recent studies, a novel VlsE
      protein IR(6) peptide-based assay has been introduced. Our aim was to evaluate
      the IR(6) peptides from three Borrelia burgdorferi sensu lato genospecies in the
      serodiagnosis of European and North American patients. Five VlsE protein IR(6)
      peptide variants representing sequences from B. burgdorferi sensu stricto, B.
      garinii, and B. afzelii were used as antigens in both IgG and IgM enzyme-linked
      immunosorbent assays (ELISA). Serum antibodies of 187 patients at different
      stages of LB from Europe and the United States were evaluated for serodiagnosis.
      For comparison samples were tested with one of the commercial IR(6) ELISAs. Three
      B. afzelii IR(6) variant peptides revealed antibodies that were concordant with
      each other. B. burgdorferi sensu stricto peptide antibodies mostly paralleled B.
      afzelii peptide antibodies, and positive values were also obtained in the
      majority of European sera. For several sera, B. garinii IR(6) peptide antibodies
      were discordant to B. afzelii peptide antibodies. The commercial IR(6) peptide
      antibody assay (C6 ELISA) results correlated better with B. burgdorferi sensu
      stricto IR(6) than with B. garinii IR(6) peptide IgG results, especially in sera
      from patients with facial palsy. Thus, antibody specificity to IR(6) peptides may
      vary according to the infecting Borrelia species. In some manifestations of the
      disease, C6 ELISA may not cover all LB cases. Evidently, the methodological
      aspects in ELISA design for peptide antibody measurements are important as well
      as the amino acids sequence of the antigen.

PMID- 17234452
TI  - Case report: parotid abscess due to Salmonella enterica serovar Enteritidis in an
      immunocompetent adult.
AB  - There are reports of increasing incidence of focal extra-intestinal infections
      from non-typhoidal salmonellae during the past two decades. We present the first
      case of a parotid abscess caused by Salmonella enterica serovar Enteritidis (S.
      Enteritidis) in an apparently immunocompetent adult without other abnormality of
      the parotid glands. A 58-year-old man was admitted to our hospital because of a 3
      day history of fever and painful swelling of the right parotid gland. His medical
      history was unremarkable. A CT scan revealed an abscess of the right parotid. S.
      Enteritidis was isolated from a sample of fluid aspirated from the parotid
      abscess under ultrasound guidance. The stool, urine, and blood cultures were
      negative. The patient was treated with ciprofloxacin 500 mg per os every 12 h for
      10 days, with complete remission of symptoms. The infection did not recur during
      3 years of follow up. Our case report adds to the literature regarding the extra
      intestinal infections with S. Enteritidis, a common non-typhoidal salmonellosis.

PMID- 17234453
TI  - New genotoxin shows diversity of bacterial attack mechanisms.
AB  - Bacteria make a wide range of toxic products that interact with eukaryotic
      cellular machinery in a precise way. These toxins interfere with key eukaryotic
      processes, such as cellular signalling components, and some directly attack the
      genome. Nougayrede and colleagues have recently identified a novel hybrid peptide
      polyketide compound from Escherichia coli that leads to DNA damage. This novel
      compound is produced by pathogenic and, most interestingly, commensal isolates.
      Although it is not yet clear how the peptide-polyketide compound functions at the
      molecular level, it is possible that it contributes to bacterial pathogenesis and
      bacterially induced carcinogenesis.

PMID- 17234454
TI  - The effect of extracorporeal photoimmunotherapy (ECP) on serum TNF-a level in
      chronic graft versus host disease (GvHD).
AB  - Graft versus host disease (GvHD) is the most prominent cause of morbidity and
      mortality after allogeneic hematopoietic cell transplantation (Allo-HCT).
      Extracorporeal photoimmunotherapy (ECP) is an alternative therapeutic modality in
      steroid and/or cyclosporin-A refractory GvHD developing after Allo-HCT. The aim
      of this study was to evaluate whether there was any relation between serum TNF-a
      levels and the response to ECP in patients with steroid refractory of extensive
      chronic GvHD. Between March 2001 and August 2003, seven patients (male: 1,
      female: 6) had ECP for treatment of steroid refractory extensive chronic GvHD.
      Five age and gender matched healthy volunteers were included in this study as the
      control group. The age of the patients ranged from 18 to 49 years. All patients
      were allografted from HLA-identical sibling donors. The median number of ECP
      sessions was 10 (8-36), consisting of two sequential cycles monthly. For
      measurement of serum TNF-a levels, blood samples were obtained both prior to ECP
      (basal) and after the first and second in all patients and in five patients after
      the 10th session. Serum TNF-a levels (Quantakine HS, R&D system, UK) were
      measured in peripheral venous blood samples by an ELISA method. ECP was given at
      a median of 5.8 months (1-14 months) after allo-HCT. No complications were seen
      during or after the ECP procedures. The median time of an ECP session was 183
      minutes. The median volume of Uvadex used per session was 4.40 ml (3.61-5.61).
      The basal mean level of TNF-a was higher in patients than in the control group
      (2.47+/-0.83 pg/ml vs. 1.75+/-0.06, p=0.05). The mean TNF-a levels decreased from
      2.47+/-0.83 pg/ml to 1.77+/-0.93 pg/ml after the initial session (p=0.045) and
      from 2.32+/-0.92 pg/ml to 1.69+/-0.93 pg/ml after the second day (p=0.015). After
      completion of the ECP sessions, extensive chronic GvHD recovered in only three
      patients. In three clinically responsive patients, the TNF-a levels were
      significantly reduced after both the second and tenth sessions. In contrast, in
      two patients not responding to ECP therapy, TNF-a levels were increased. In order
      to report whether these changes in TNF levels is an early predictor for
      evaluation of the efficacy of ECP in extensive chronic GvHD, TNF-a levels should
      be studied in a larger series.

PMID- 17234455
TI  - Frequent platelet apheresis donations in volunteer donors with hemoglobin < 125
      g/l are safe and efficient.
AB  - BACKGROUND: For safety reasons, volunteer whole blood donation requires a minimal
      hemoglobin (Hb) concentration of > 125 g/l. Since the first generation of
      apheresis devices caused significant RBC loss, the same Hb eligibility criterion
      was applied for apheresis donors (APH-D). However, this may exclude many suitable
      platelet donors (PLT-D) due to low hemoglobin concentration. STUDY DESIGN AND
      METHODS: Covering a three year period (1999-2001), the APH-Ds having Hb < or =
      125 g/l and donating platelet concentrates (PLC) were retrospectively analyzed
      focusing on donor safety and donation efficacy. The apheresis procedures were
      performed using AMICUS and CobeSpectra devices, targeting a PLT yield of 3 x
      10(11) PLT per donation. Predonation PLT- and Hb-concentrations were investigated
      by regression analysis. In addition, hematological changes due to repetitive
      apheresis donation (APH) were assessed. RESULTS: From 1999 to 2001, 1864
      volunteer PLT-Ds donated 13,716 PLCs. Three hundred and two PLT-Ds (16%) donating
      2013 PCs (14.7%) had predonation Hb < or = 125 g/l at the initial donation and
      constituted the study population. Ninety-five percent were women. Despite
      repetitive APHs of up to 20 procedures per PLT-D and with donation intervals of
      <60 days, the individual Hb concentration did not change significantly throughout
      the observation period. There was no statistically significant reverse
      correlation between predonation PLT concentration and the degree of anemia.
      CONCLUSIONS: The eligibility criterion of Hb > or = 125 g/l for APH-D is not
      justified and leads to exclusion of mainly female volunteer apheresis donors.
      Repetitive PLT-APH does not negatively affect Hb concentration. Selective
      recruitment of borderline anemic donors into a PLT-APH program can be done safely
      and offers an alternative donation opportunity to otherwise excluded volunteer
      blood donors.

PMID- 17234456
TI  - World apheresis registry report.
AB  - The establishment of national apheresis registries has been helpful to learn
      about therapeutic profiles and adverse event incidences. During 2003, the World
      Apheresis Registry was established and centers from all countries were invited to
      participate to register their apheresis activities (at www.iml.umu.se/medicin).
      MATERIAL: In this paper, we will report and analyze the first data retrieved from
      three centers, in 2 European countries, that registered a total of 388
      therapeutic apheresis treatments in 122 patients, 95% due to acute indications.
      Statistical analyses were performed using an independent Student t-test and
      Fisher's test. A p-value of less than 0.05 was considered significant. RESULTS:
      Fifty percent of the treated patients were women. The mean age of the patients
      was 51 years (+/-17, range 16-84) and there was no difference between genders (w
      50.4, m 51.6 years). Diagnoses for treatment were mainly neurological and
      vasculitis. In 63% peripheral access was used with a central double lumen
      catheter, 22% in the jugular vein, 8% in the subclavian vein and 6% the femoral
      vein. Significant inter-center differences were seen in regard to the access
      used. The main technique used was centrifugation for conventional plasma exchange
      (86%), while other modes were leukapheresis, erythrapheresis, platelet apheresis,
      LDL-apheresis and adsorption of antibodies. Citrate was the only anticoagulant in
      92%. During plasma exchange procedures using centrifugation, replacement was by
      albumin only (58%) or plasma, the latter often in combination with albumin (42%).
      Adverse events (AEs) were noted in 11% of the procedures. Patients with
      hypocalcaemia side effects with tingling sensations were included in those data
      as mild AE and as moderate AEs if they received calcium (Ca) medication. No
      patient died due to adverse effects. A mild AE was present in 1.8% and moderate
      in 8.5%. During two procedures (0.5%), the AE was considered severe and therefore
      the procedure was interrupted. If those with AEs due to lower calcium were
      removed from analyses, 6.4% had AEs. Significantly more AEs were found when
      plasma was used as a replacement fluid (p=0.017, RR 2.05, CI 1.17-3.60). There
      were no differences in the incidence of AEs between genders. The number of
      procedures was too small to allow sub analyses of AEs in relation to the
      diagnoses. Adverse events were not related to the procedure used (p=0.095). Those
      who received additional Ca infusion during the procedure had no AEs (40 sessions)
      while the others who received no prophylactic Ca had an AE on 45 occasions
      (p=0.0141, RR 1.116, CI 1.08-1.15). CONCLUSION: Data from the registry shows that
      centers have various approaches to apheresis. One can learn from each other's
      experience to reduce side effects and improve efficacy. From these data we noted
      that prophylactic Ca infusion reduced side effects.

PMID- 17234458
TI  - CD4(+)CD25(+)FoxP3(+) regulatory T cells suppress Mycobacterium tuberculosis
      immunity in patients with active disease.
AB  - CD4(+)CD25(+) regulatory T cells (Treg) play a central role in the prevention of
      autoimmunity and in the control of immune responses by down-regulating the
      function of effector CD4(+) or CD8(+) T cells. The role of Treg in Mycobacterium
      tuberculosis infection and persistence is inadequately documented. Therefore, the
      current study was designed to determine whether CD4(+)CD25(+)FoxP3(+) regulatory
      T cells may modulate immunity against human tuberculosis (TB). Our results
      indicate that the number of CD4(+)CD25(+)FoxP3(+) Treg increases in the blood or
      at the site of infection in active TB patients. The frequency of
      CD4(+)CD25(+)FoxP3(+) Treg in pleural fluid inversely correlates with local MTB
      specific immunity (p<0.002). These CD4(+)CD25(+)FoxP3(+) T lymphocytes isolated
      from the blood and pleural fluid are capable of suppressing MTB-specific IFN
      gamma and IL-10 production in TB patients. Therefore, CD4(+)CD25(+)FoxP3(+) Treg
      expanded in TB patients suppress M. tuberculosis immunity and may therefore
      contribute to the pathogenesis of human TB.

PMID- 17234459
TI  - Vascular endothelium summary statement III: Cancer prevention and control.
AB  - The biology of vascular endothelium can be modulated through the use of
      pharmacologic agents. Whereas this has been explored to reasonable extent in
      cardiovascular disease, it is clear that the ability to modulate vascular
      endothelium for the purpose of cancer prevention is in its early stages. Among
      the unanswered questions, we do not understand under what circumstances such
      pharmacologic interventions might best be started; nor, how long such
      interventions might be used for a given individual. We present concepts for
      further exploration in the use of endothelial-active agents for cancer prevention
      and control; and, strategies for public health practice and research in this
      area.

PMID- 17234460
TI  - The autonomic nervous system and inflammatory bowel disease.
AB  - Crohn's disease and ulcerative colitis, collectively known as inflammatory bowel
      disease (IBD), are chronic, recurring, inflammatory conditions of the intestine.
      The precise mechanisms underlying the pathogenesis of IBD are not yet clear but
      they are believed to involve a number of precipitating factors, most notably
      genetic susceptibility and environmental influences. The autonomic nervous system
      (ANS) has long been known as a critical regulator of intestinal function and much
      evidence now exists to suggest that it also plays an important role in the
      development of IBD. Dramatic changes in the ANS in IBD are apparent from the
      cellular to the molecular level ultimately leading to altered communication
      between the ANS and effector cells of the intestine. This review aims to
      synthesize the current understanding of the pathogenesis of IBD with a particular
      emphasis on the role that the ANS plays in the progression of these diseases.

PMID- 17234461
TI  - Electrical and pharmacological properties of petrosal ganglion neurons that
      innervate the carotid body.
AB  - The petrosal ganglion (PG) contains the somata of primary afferent neurons that
      innervate the chemoreceptor (glomus) cells in the carotid body (CB). The most
      accepted model of CB chemoreception states that natural stimuli trigger the
      release of one or more transmitters from glomus cells, which in turn acting on
      specific post-synaptic receptors increases the rate of discharge in the nerve
      endings of PG neurons. However, PG neurons that project to the CB represent only
      small fraction (roughly 20%) of the whole PG and their identification is not
      simple since their electrophysiological and pharmacological properties are not
      strikingly different as compared with other PG neurons, which project to the
      carotid sinus or the tongue. In addition, differences reported on the actions of
      putative transmitters on PG neurons may reflect true species differences.
      Nevertheless, some experimental strategies have contributed to identify and
      characterize the properties of PG neurons that innervate the CB. In this review,
      we examined the electrophysiological properties and pharmacological responses of
      PG neurons to putative CB excitatory transmitters, focusing on the methods of
      study and species differences. The evidences suggest that ACh and ATP play a
      major role in the fast excitatory transmission between glomus cells and
      chemosensory nerve endings in the cat, rat and rabbit. However, the role of other
      putative transmitters such as dopamine, 5-HT and GABA is less clear and depends
      on the specie studied.

PMID- 17234462
TI  - Direct quantification of dimethylsulfoniopropionate (DMSP) in marine micro- and
      macroalgae using HPLC or UPLC/MS.
AB  - A simple method for the direct quantification of dimethylsulfinopropionate (DMSP)
      using HPLC or UPLC coupled to UV and/or MS detection is introduced. The protocol
      is applied for the determination of DMSP from marine micro- and macroalgae. The
      method is based on the derivatisation of DMSP using 1-pyrenyldiazomethane
      followed by reversed phase HPLC or UPLC separation. The detection limit is 590
      nM, corresponding to 1 ng DMSP per injection. Using a combination of UV and MS
      detection the calibration curves were linear in the range of 2.93 microM to 11.7
      mM concentrations. We show that direct determination of DMSP is possible from
      macroalgal tissue and microalgal cultures if DMSP-lyase activity is suppressed
      during work-up.

PMID- 17234463
TI  - Compensatory secondary structure alterations in protein glycation.
AB  - Glycation, a local covalent interaction, leads to alterations in secondary and
      tertiary structures of hemoglobin, the changes produced by fructose being more
      pronounced than those caused by glucose. The Stokes diameter of hemoglobin
      increases upon glycation from 7 to 14 nm and a concurrent inter-chain cross
      linking and heme loss are also observed, particularly in the later stage of
      glycation. An initial increase of tryptophan (trp) fluorescence was observed in
      both glucation and fructation. In case of frucation however there was a decrease
      in tryptophan fluorescence that was accompanied by an increase in fluorescence of
      the advanced glycosylation end products (AGEs). This fluorescence behavior is
      indicative of energy transfer between tryptophan and the AGEs formed during the
      late stage of glycation. Emergence of an isosbestic point in the fluorescence
      spectra (taken at different time intervals) implies existence of two distinct
      glycation stages. The late glycation stage is also marked by an increase of beta
      structure and random coil at the expense of alpha helix. It is further observed
      that this compensatory loss of alpha helix (reported for the first time) and
      increase in beta sheet and random coil elements depend on the number of solvent
      accessible glycation sites (rather than total number of such sites) and the
      subunit assembly of the protein.

PMID- 17234464
TI  - Nanostructure, dissolution and morphology characteristics of microcidal silver
      films deposited by magnetron sputtering.
AB  - Novel microcidal silver films for burn dressings have been produced by magnetron
      sputtering. The nanostructure and dissolution characteristics of these films
      exhibiting antimicrobial behavior were studied as a function of the process
      conditions, namely, gas composition, gas pressure and input power, using
      transmission electron microscopy (TEM), high-resolution scanning electron
      microscopy, X-ray photoelectron spectroscopy (XPS) and resistivity. TEM revealed
      that bioactive films were nanocrystalline, with a grain size of the order of 15nm
      and the presence of twins. Surface morphology studies before and after
      dissolution suggested that bioactive films released silver at therapeutic levels
      in the form of nanoparticles or grains. Chemical species identification with XPS
      showed that the biologically active films were metallic in nature. The importance
      of oxygen in the sputtering environment, the resultant nanostructure and presence
      of twins are discussed to explain the unique antimicrobial properties of these
      silver films.

PMID- 17234465
TI  - In vitro hydroxyapatite forming ability and dissolution of tobermorite
      nanofibers.
AB  - In this paper, fiber-like and dispersible tobermorite
      (Ca(5)(Si(6)O(16))(OH)(2).4H(2)O), 80-120 nm in diameter and up to tens of
      micrometers in length was prepared by a hydrothermal microemulsion method. In
      vitro bioactivity of the nanofibers were evaluated by examing the hydroxyapatite
      (HAp) forming ability on the surface after soaking in simulated body fluid (SBF)
      for various periods. After soaking in SBF, the nanofibers were completely covered
      by bonelike hydroxycarbonate apatite (HCA) layers, and the nanofibers after
      soaking still kept stability in fibrous morphology. The dissolution of the
      nanofibers reached about 24.5% after soaking in SBF for 14 days. The results
      suggested that the tobermorite nanofibers exhibited certain desirable
      characteristics, including bioactivity, degradability and stability in
      morphology, and are a potential candidate for a reinforcement material in the
      development of novel bioactive and degradable composites for biomedical
      applications.

PMID- 17234466
TI  - Elastic deformation behaviour of Ti-24Nb-4Zr-7.9Sn for biomedical applications.
AB  - In this paper, the elastic deformation behaviour of a recently developed beta
      type titanium alloy Ti-24Nb-4Zr-7.9Sn (wt.%) that consists of non-toxic elements
      and is intended for biomedical applications is described. Tensile tests show that
      this alloy in the as hot-rolled state exhibits peculiar non-linear elastic
      behaviour with maximum recoverable strain up to 3.3% and incipient Young's
      modulus of 42GPa. Solution treatment at high temperature has trivial effect on
      super-elasticity but decreases strength and slightly increases the incipient
      Young's modulus. Ageing treatment in the (alpha+beta) two-phase field increases
      both strength and Young's modulus and results in a combination of high strength
      and relatively low elastic modulus. In spite of the formation of the alpha phase,
      short time ageing has no effect on super-elasticity, whereas the non-linear
      elastic behaviour transforms gradually to normal linear elasticity with the
      increase of ageing time. We suggest sluggish, partially reversible processes of
      stress-induced phase transformation and/or incipient kink bands as the origin of
      the above peculiar elastic behaviour.

PMID- 17234467
TI  - Effect of fatigue loading and associated matrix microdamage on bone blood flow
      and interstitial fluid flow.
AB  - Functional adaptation of bone to cyclic fatigue involves a complex physiological
      response that is targeted to sites of microdamage. The mechanisms that regulate
      this process are not understood, although lacunocanalicular interstitial fluid
      flow is likely important. We investigated the effect of a single period of cyclic
      fatigue on bone blood flow and interstitial fluid flow. The ulnae of 69 rats were
      subjected to cyclic fatigue unilaterally using an initial peak strain of -6000
      muepsilon until 40% loss of stiffness developed. Groups of rats (n=23 per group)
      were euthanized immediately after loading, at 5 days, and at 14 days. The
      contralateral ulna served as a treatment control, and a baseline control group
      (n=23) that was not loaded was also included. After euthanasia, localization of
      intravascular gold microspheres within the ulna (n=7 rats/group) and tissue
      distribution of procion red tracer were quantified (n=8 rats/group).
      Microcracking, modeling, and remodeling (Cr.S.Dn, microm/mm(2), Ne.Wo.B.T.Ar,
      mm(2), and Rs.N/T.Ar, #/mm(2) respectively) were also quantified histologically
      (n=8 rats/group). Cyclic fatigue loading induced hyperemia of the loaded ulna,
      which peaked at 5 days after loading. There was an associated overall decrease in
      procion tracer uptake in both the loaded and contralateral control ulnae. Tracer
      uptake was also decreased in the periosteal region, when compared with the
      endosteal region of the cortex. Pooling of tracer was seen in microdamaged bone
      typically adjacent to an intracortical stress fracture at all time points after
      fatigue loading; in adjacent bone tracer uptake was decreased. New bone formation
      was similar at 5 days and at 14 days, whereas formation of resorption spaces was
      increased at 14 days. These data suggest that a short period of cyclic fatigue
      induces bone hyperemia and associated decreased lacunocanalicular interstitial
      fluid flow, which persists over the time period in which osteoclasts are
      recruited to sites of microdamage for targeted remodeling. Matrix damage and
      development of stress fracture also interfere with normal centrifugal fluid flow
      through the cortex. Changes in interstitial fluid flow in the contralateral ulna
      suggest that functional adaptation to unilateral fatigue loading may include a
      more generalized neurovascular response.

PMID- 17234468
TI  - Identification of a basal-like subtype of breast ductal carcinoma in situ.
AB  - Microarray profiling of invasive breast carcinomas has identified subtypes
      including luminal A, luminal B, HER2-overexpressing, and basal-like. The poor
      prognosis, basal-like tumors have been immunohistochemically characterized as
      estrogen receptor (ER)-negative, HER2/neu-negative, and cytokeratin 5/6-positive
      and/or epidermal growth factor receptor (EGFR)-positive. The aim of this study
      was to determine the prevalence of basal-like ductal carcinoma in situ in a
      population-based series of cases using immunohistochemical surrogates. A total of
      245 pure ductal carcinoma in situ cases from a population-based, case-control
      study were evaluated for histologic characteristics and immunostained for ER,
      HER2/neu, EGFR, cytokeratin 5/6, p53, and Ki-67. The subtypes were defined as:
      luminal A (ER+, HER2-), luminal B (ER+, HER2+), HER2 positive (ER-, HER2+), and
      basal-like (ER-, HER2-, EGFR+, and/or cytokeratin 5/6+). The prevalence of breast
      cancer subtypes was basal-like (n = 19 [8%]); luminal A, n = 149 (61%); luminal
      B, n = 23 (9%); and HER2+/ER-, n = 38 (16%). Sixteen tumors (6%) were
      unclassified (negative for all 4 defining markers). The basal-like subtype was
      associated with unfavorable prognostic variables including high-grade nuclei (P <
      .0001), p53 overexpression (P < .0001), and elevated Ki-67 index (P < .0001).
      These studies demonstrate the presence of a basal-like in situ carcinoma, a
      potential precursor lesion to invasive basal-like carcinoma.

PMID- 17234469
TI  - Expression of glutathione S-transferase pi and glutathione synthase correlates
      with survival in early stage non-small cell carcinomas of the lung.
AB  - The glutathione S-transferase (GST) family of genes encode for detoxification
      enzymes that protect against reactive oxygen species and influence host
      susceptibility to carcinogens, including tobacco smoke. It has not been
      determined whether isoenzyme GST-pi or glutathione synthase (GSH2) expression by
      tumor cells bears a relationship to survival. A total of 201 non-small cell lung
      cancers (NSCLC) with long-term follow-up were immunostained with antibodies to
      GST-pi and GSH2 using standard immunostaining techniques. Results were graded
      semiquantitatively using a scale of 0 to 3 (0 < or = 10%; 1 = 10%-50%; 2 = 51%
      80%; 3 > or = 80%) for both nuclear and cytoplasmic staining. Results were
      correlated with patient survival using Kaplan-Meier analysis. Nuclear staining
      with GST-pi in greater than 10% of the cells was closely associated with
      decreased survival (P = .02) in stage I and II squamous cell carcinomas (n = 40).
      Cytoplasmic staining showed a similar trend that did not reach statistical
      significance. No significant correlation between GST-pi staining and survival was
      determined for other histologic types of NSCLC. Cytoplasmic GSH2 staining in
      greater than 80% of tumor cells was associated with a trend toward improved
      survival for stage I adenocarcinoma (P = .08) but did not show a relationship to
      survival for other histologic types of NSCLC. GST-pi expression predicts
      prognosis in stage I and II squamous cell lung carcinoma, and GSH2 expression may
      indicate better survival in early stage adenocarcinoma of the lung. Manipulation
      of GST-pi and GSH2 may be a potential basis for treatment of some NSCLC.

PMID- 17234470
TI  - Medical students' perceptions of pathology.

PMID- 17234472
TI  - Health-related quality of life: a closer look at related research in patients who
      have undergone the Fontan operation over the last decade.
AB  - The advancements in surgical technique and perioperative care have significantly
      improved the survival of children with single ventricle (SV) congenital heart
      disease (CHD) over the past decade. The population who have undergone the Fontan
      operation are growing into adulthood and facing many unique challenges. Past
      research has focused on functional and neurodevelopmental outcomes with
      inferences made to health-related quality of life (HRQOL). With the population
      who have undergone the Fontan operation surviving into adulthood, little research
      has been directed toward the self-report of HRQOL in adolescents and young adults
      after surgical palliation. Questions still remain on how these patients will
      transition into adulthood and whether they will live normal productive lives.
      This article reviews the literature related to HRQOL in the SV subgroup of CHD.
      In addition, an overview of newly developed disease-specific HRQOL instruments is
      presented as well as limitations and future research in HRQOL of the SV Fontan
      population.

PMID- 17234473
TI  - A comparison of health-related quality of life between older adults with heart
      failure and healthy older adults.
AB  - BACKGROUND: Health-related quality of life (HRQOL) in older adults with heart
      failure may be affected by a variety of variables including aging. It is
      important to determine the unique impact of heart failure to more effectively
      improve HRQOL in this population. OBJECTIVE: The purpose of this study was to
      compare HRQOL and physical, psychologic, clinical, and sociodemographic status in
      older adults with and without heart failure. METHODS: The HRQOL of 90 older
      adults with heart failure and 116 healthy older adults was compared. The factors
      best associated with HRQOL in each group were determined using multiple
      regression model. RESULTS: HRQOL was substantially worse among older adults with
      heart failure than among healthy older adults. Older adults with heart failure
      had more severe physical and emotional symptoms, poorer functional status, and
      worse health perceptions. Physical symptom status was the strongest predictor of
      HRQOL in both groups. In addition, in older adults with heart failure, physical
      symptom status, age, and anxiety were related to HRQOL. CONCLUSION: The poor
      HRQOL seen in patients with heart failure is not just a reflection of aging.
      Comprehensive interventions targeted toward the factors that specifically
      negatively impact HRQOL are essential in older adults with heart failure.

PMID- 17234474
TI  - Interpretation of symptoms and delay in seeking treatment by patients who have
      had a stroke: exploratory study.
AB  - OBJECTIVES: The purpose of this exploratory study was to examine the knowledge of
      stroke symptoms and risk factors in patients who have had a stroke and examine
      factors contributing to longer patient delay times during stroke. METHODS:
      Patients who had experienced an ischemic stroke and were able to understand and
      respond to questions were eligible to participate. A structured interview was
      used to identify patients' knowledge about symptoms and causes of stroke and the
      sequence of events from recognizing symptoms to accessing the emergency
      department (ED). RESULTS: Twenty-six women and 12 men participated. Patients'
      ages ranged from 33 to 84 years (M = 62), and 44.7% were African-American, 39.5%
      were non-Hispanic white, and 15.8% were Latino. Only 60.5% of patients accurately
      identified one risk factor for stroke, and 55.3% were able to accurately identify
      at least one symptom of stroke. Patients' median delay time from the onset of
      symptoms to admission for stroke in the ED was 16 hours; only 12 patients (31.6%)
      accessed the ED in less than 2 hours. The most frequently reported symptom was
      weakness, which was experienced by 60% of the sample. The variables that were
      significantly related to longer delay time were as follows: African-American or
      Latino; lack of recognition of the seriousness of the symptoms; primary symptom
      was not motor; did not use 911; and resided in an urban setting. Logistic
      regression analysis showed that nonmotor symptoms as the primary symptom and not
      using 911 were significant predictors of delay longer than 2 hours. Someone other
      than the patient made the decision to seek treatment in 66% of the situations.
      CONCLUSION: Educational interventions should be targeted to high-risk groups and
      their family members and should include not only stroke symptoms but also an
      action plan (call 911) when stroke symptoms are experienced.

PMID- 17234475
TI  - The normative distribution of chest tube drainage volume after coronary artery
      bypass grafting.
AB  - BACKGROUND: Little evidence exists to describe expected volumes of chest tube
      (CT) drainage after coronary artery bypass grafting (CABG). OBJECTIVES: The study
      objective was to map the trajectory of CT drainage volumes from insertion to
      removal after CABG. DESIGN: This was a retrospective, descriptive study.
      PATIENTS: The study included 239 patients who underwent CABG at a single
      metropolitan hospital in Melbourne, Australia. RESULTS: The sample (N = 234),
      aged 68.7 years (standard deviation [SD] 9.9), was predominantly male (N = 185,
      79.1%). The mean duration of CT insertion was 45.2 hours (SD 26.7), and total
      drainage volume was 1300.6 mL (SD 763.8). Drainage volumes plateau to 31 mL per
      hour, 8 hours after surgery. From 24 to 48 hours, the mean drainage was 21 mL per
      hour. Drainage volumes varied between genders. CONCLUSIONS: Evidence of similar
      drainage patterns in other populations is difficult to locate. If the pattern of
      drainage shown in this study is consistent, experimental intervention studies
      comparing standard removal time and earlier removal are recommended. If not,
      prospective collection of relevant preoperative, intraoperative, and
      postoperative factors across multiple sites is necessary to determine which
      patient or practice variations influence CT drainage patterns after CABG.

PMID- 17234476
TI  - Stress-related cardiomyopathy.
AB  - Stress-related cardiomyopathy is underdiagnosed in the white population.
      Recently, an increasing awareness of this syndrome was noted in the United
      States. Stress-related cardiomyopathy was found mostly in women after an
      immediate stress. The available literature has indicated excellent short-term
      prognosis and full recovery. We report the case of a 56-year-old white woman with
      acute pancreatitis, whose condition necessitated an endoscopic retrograde
      cholangiopancreatography procedure. Shortly after she received counseling for
      this procedure, acute retrosternal chest pain and shortness of breath developed.
      She had ischemic abnormalities on electrocardiography and mild cardiac biomarkers
      elevation. Subsequent cardiac catheterization revealed normal coronary arteries
      but reduced ejection fraction (25%), and typical apical ballooning was noted. Ten
      days later, the left ventricular function completely normalized (ejection
      fraction of 55%).

PMID- 17234477
TI  - Family presence and surveillance during weaning from prolonged mechanical
      ventilation.
AB  - OBJECTIVES: The research was designed to describe the care and communication
      processes during weaning from long-term mechanical ventilation (LTMV). A portion
      of those findings, specifically, how family members interact with the patient and
      respond to the ventilator and associated intensive care unit bedside equipment
      during LTMV weaning, are reported here. METHODS: Ethnography was conducted in a
      medical intensive care unit (MICU) and step-down MICU following 30 adults who
      were being weaned from LTMV (>4 days). Data collection involved field
      observations conducted from November 2001 to July 2003; interviews with patients,
      family members, and MICU clinicians; and clinical record review. RESULTS: Family
      members were present at the patients' bedside during 46% of weaning trials and
      interacted with patients through touch, talking, and surveillance. Families'
      bedside surveillance activities were interpretive of numeric monitor displays and
      laboratory values, protective of patient safety and comfort, and often focused
      exclusively on weaning. Interpretive language and surveillance were learned from
      and imitative of clinician behaviors. Clinicians characterized the family's
      presence as helpful, a hindrance, or having no effect on the weaning process.
      Quantitative analysis using random coefficient modeling examining the effect of
      family presence on length of weaning trials showed significantly longer daily
      weaning trials when families were present (P < .0001). CONCLUSION: Critical care
      clinicians influence families' acquisition of interpretive surveillance skills at
      the bedside of patients who are being weaned from LTMV. This study provides a
      potentially useful conceptual framework of family behaviors with long-term
      critically ill patients that could enhance the dialogue about family-centered
      care and guide future research on family presence in the intensive care unit.

PMID- 17234478
TI  - Detection of dopamine receptor subtypes in the rat diaphragm.
AB  - BACKGROUND: The administration of dopamine using an in vivo animal model has been
      shown to prevent and treat diaphragm fatigue. OBJECTIVE: With the knowledge that
      dopamine stimulates alpha- and beta-adrenergic and dopamine receptors, the
      purpose of this study was to investigate whether dopamine receptors are present
      in the diaphragm. In addition, if dopamine receptors were detected, we would
      identify the class and subtype of dopamine receptors. METHOD: Radioligand binding
      studies and reverse transcriptase polymerase chain reaction experiments were
      used. RESULTS: The receptor binding studies were unable to establish whether
      dopamine receptors were present in the diaphragm. However, highly sensitive
      reverse transcriptase polymerase chain reaction experiments demonstrated that
      D(1)-like receptors (D(1) and D(5) receptors) were detected in the diaphragm.
      CONCLUSIONS: This study is the first to report the class and specific subtype of
      dopamine receptors found in the diaphragm. By identifying dopamine receptors in
      the diaphragm, we have a better understanding of the mechanisms by which dopamine
      treats and prevents diaphragm fatigue.

PMID- 17234479
TI  - Coccidioides immitis fungemia: clinical features and survival in 33 adult
      patients.
AB  - Coccidioides immitis is a fungus endemic to the southwestern United States.
      Susceptible hosts, including blacks, Hispanics, Filipinos, Native Americans, and
      those with compromised immunity, may develop disseminated disease, including
      fungemia. We retrospectively reviewed the records of all patients (n = 33) with
      Coccidioides immitis fungemia (CIF) at a 550-bed public hospital in Phoenix,
      Arizona, from 1990 to 2002. This is the largest reported series of CIF. The
      purpose of the study was to review the incidence, signs, symptoms, and outcomes
      of CIF. Twenty-nine patients had human immunodeficiency virus infection. CIF was
      associated with sepsis, end-stage alcoholic liver disease, and diabetes in four
      patients. Survival was poor; 24 of the 33 patients died within 28 days. CIF
      manifested as a systemic inflammatory response syndrome with progressive
      cardiorespiratory failure. Despite fluid loading, infusion of vasoactive agents,
      and mechanical ventilation with positive end-expiratory pressure, patients
      typically experienced a rapidly progressive course and death. CIF portends an
      ominous prognosis and typically occurs in the setting of advanced human
      immunodeficiency virus or medical or surgical crises.

PMID- 17234480
TI  - Herpes simplex virus (HSV) pneumonia in a heart transplant: diagnosis and
      therapy.
AB  - Organ transplants are frequently complicated by viral infections. The period of
      maximum immunosuppression, 1 to 6 months posttransplantation, predisposes one to
      intracellular pathogens. The most common intracellular viral pathogens in
      transplant recipients include cytomegalovirus (CMV), herpes simplex virus (HSV),
      and respiratory syncytial virus (RSV). Cytomegalovirus and HSV are common viral
      pathogens in the early transplant period (0-1 month posttransplant). Although
      respiratory syncytial virus commonly presents in the late posttransplant period
      (> or =6 months posttransplant), HSV pneumonia may be acquired in organ
      transplants by endogenous reactivation caused by immunosuppression or may be
      introduced from colonized oropharyngeal secretions into the lower respiratory
      tract during intubation in patients on ventilators. In ventilated patients
      without severe preexisting lung disease, HSV pneumonia presents with otherwise
      unexplained profound/prolonged hypoxemia or "failure to wean." As other viral
      pneumonias, HSV pneumonia is characterized by profound hypoxemia requiring a high
      FIo(2), and a highly increased A-a gradient (> or =30). These findings are
      indicative of an oxygen diffusion defect typical of noninfectious (eg,
      sarcoidosis) or infectious disorders (eg, HSV, cytomegalovirus, respiratory
      syncytial virus, Pneumocystis (carinii) jiroveci pneumonia) primarily affecting
      the interstitium of the lung. We present a case of HSV pneumonia in a heart
      transplant recipient and include a review of the clinical presentation,
      diagnostic findings, and therapy of HSV pneumonia.

PMID- 17234481
TI  - Unusual scapular metastasis as initial manifestation of advanced nonseminomatous
      germ cell tumor of the mediastinum.
AB  - Primary malignant germ cell tumors of the mediastinum are relatively rare,
      occurring predominantly in young male adults, and have a poor prognosis. We
      present a case of a 27-year-old man who initially experienced a persistent,
      intractable painful sensation over the right lower scapula despite taking an
      analgesic agent for 2 months. A scapular x-ray film and a whole-body bone scan
      showed an expansile osteolytic lesion. Excisional biopsy of the scapula revealed
      a metastatic carcinoma, suggestive of nonseminomatous germ cell tumor origin.
      Further examination of the whole abdomen and bilateral testes were negative.
      Chest computed tomography and magnetic resonance imaging showed a primary tumor
      mass in the anterior mediastinum. Chemotherapy with cisplatin, bleomycin, and
      etoposide was administered for six courses. The mediastinal tumor mass was
      markedly reduced in size and remission without evidence of tracer uptake by
      [(18)F]fluorodeoxyglucose positron emission tomography examination. Six months
      after chemotherapy, the patient received advanced surgical intervention to remove
      the mediastinal tumor, the pathologic features of which were similar to the
      previous scapular lesion. He was doing well at 1-year follow-up.

PMID- 17234482
TI  - Wenckebach variant.

PMID- 17234483
TI  - Healthcare utilization and costs for women with a history of intimate partner
      violence.
AB  - OBJECTIVE: To determine the healthcare utilization and medical care costs of
      women with a history of intimate partner violence (IPV) compared to women without
      a history of IPV. DESIGN: Longitudinal cohort study. SETTING: Mixed-model health
      maintenance organization. PARTICIPANTS: Over 3000 (3333) women aged 18 to 64
      years with > or = 3 year's cumulative enrollment prior to the survey, at least 1
      year of which was after the 18th birthday. MAIN EXPOSURE: IPV since age 18 as
      determined from responses to telephone interview using questions from the
      Behavioral Risk Factor Surveillance System and also the Women's Experience with
      Battering Scale. OUTCOME MEASURES: Healthcare utilization and costs (from
      automated data) during the time that IPV occurred and following its cessation,
      compared to healthcare utilization for women who did not report IPV since age 18.
      RESULTS: A total of 1546 women reported IPV in their lifetime; at the time of
      interview, IPV had ceased in 87% of women, on average 16.0 years prior to
      interview. Healthcare utilization was higher for all categories of service during
      IPV compared to women without IPV, and decreased over time after cessation of
      IPV. However, healthcare utilization was still 20% higher 5 years after women's
      abuse ceased compared to women without IPV. Adjusted annual total healthcare
      costs were 19% higher in women with a history of IPV (amounting to $439 annually)
      compared to women without IPV. Based on prevalence for IPV of 44%, the excess
      costs due to IPV are approximately $19.3 million per year for every 100,000 women
      enrollees aged 18-64. CONCLUSIONS: Women with a history of IPV had significantly
      higher healthcare utilization and costs, continuing long after IPV ended. Given
      its high prevalence, IPV has a major impact on medical care resource utilization
      and efforts to prevent its occurrence and consequences are clearly indicated.

PMID- 17234484
TI  - Inequities in CHD incidence and case fatality by neighborhood deprivation.
AB  - BACKGROUND: Research has not firmly established whether living in a deprived
      neighborhood predicts the incidence and case fatality of coronary heart disease
      (CHD), and whether effects vary across sociodemographic groups. METHODS:
      Prospective follow-up study of all Swedish women and men, aged 35 to 74 (1.9
      million women, 1.8 million men). Women and men, without a history of CHD, were
      assessed on December 31, 1995, and followed from January 1, 1996 through December
      31, 2000, for first fatal or nonfatal CHD event (130,024 cases); data were
      analyzed in 2006. Neighborhood-level deprivation (index of education, income,
      unemployment, welfare assistance) was categorized as low, moderate, and high
      deprivation. RESULTS: Age-standardized CHD incidence was 1.9 times higher for
      women and 1.5 times higher for men in high- versus low-deprivation neighborhoods;
      1-year case fatality from CHD was 1.6 times higher for women and 1.7 times higher
      for men in high versus low deprivation neighborhoods. The higher incidence in
      more deprived neighborhoods was observed across all individual-level
      sociodemographic groups (age, marital status, family income, education,
      immigration status, mobility, and urban/rural status). In multilevel logistic
      regression models, neighborhood deprivation remained significantly associated
      with both CHD incidence and case fatality for women and men after adjusting for
      the seven sociodemographic factors (p values <0.01). Effects were slightly
      stronger for women than men in an ancillary analysis that tested for gender
      differences. CONCLUSIONS: The clustering of CHD and subsequent mortality among
      adults in deprived neighborhoods raises important clinical and public health
      concerns, and calls for a reframing of health problems to include neighborhood
      social environments, as they may affect health.

PMID- 17234485
TI  - Impact of influenza immunization on medical expenditures among Medicare elderly,
      1999-2003.
AB  - BACKGROUND: The impact of influenza immunization on expenditures for inpatient,
      outpatient, and professional services among elderly Medicare beneficiaries
      between 1999 and 2003 was examined. METHODS: Data were from independent annual
      survey samples of 175,000 beneficiaries. Response rates ranged from 64% to 71%.
      Survey data included beneficiaries' demographics, education, supplemental
      insurance, perceived health, and influenza vaccination. Baseline measures,
      derived from Medicare claims for the year prior to influenza season, included
      service utilization, comorbidities, influenza immunization, and health status.
      The outcome measure was medical expenditures for acute and chronic respiratory
      conditions (ACRCs) for each 33-week annual influenza season. RESULTS: Total
      expenditures for ACRCs were lower among the immunized population during all four
      seasons. The amount and statistical significance of the savings varied with the
      severity of the virus and the vaccine match to the prevalent influenza strains.
      During the 1999-2000 influenza season, which had the most severe virus and a
      close vaccine match, average costs for ACRCs were $88 lower among immunized
      beneficiaries than among nonimmunized beneficiaries (equivalent to a 3.06%
      savings). During the 2002-2003 season, which had a less severe virus but the
      highest vaccine match rate, average costs for ACRCs were $103 lower for immunized
      beneficiaries than for nonvaccinated beneficiaries (equivalent to a 3.12%
      savings). The relative reduction in ACRC expenditures among vaccinated
      beneficiaries is attributable to less frequent use of inpatient services.
      CONCLUSIONS: In addition to improving the health of older Americans, meeting the
      Healthy People 2010 influenza immunization goal of 90% among the elderly should
      also result in lower Medicare expenditures.

PMID- 17234486
TI  - Special healthcare taxing districts: association with population health status.
AB  - BACKGROUND: Locally generated special healthcare taxes are an important component
      of community infrastructure, but their impact on the health status of populations
      has not been systematically addressed. METHODS: Florida counties were segmented
      on the basis of the use/nonuse of locally generated tax dollars for health care
      during the 1992-1996 period and analyzed in 2004. Linear mixed-effects regression
      analysis was used to test a model in which taxing behavior served as the primary
      predictor variable for total age-adjusted and selected cause-specific mortality.
      Race/ethnicity, rurality, poverty, access to a public hospital, and physician
      availability were controlled. RESULTS: Local taxation was associated with lower
      total age-adjusted mortality, and lower mortality for the major causes of death,
      except stroke, when compared to the state mean. Local taxation is protective
      relative to total age-adjusted mortality (odds ratio [OR]=0.63, 95% confidence
      interval [CI]=0.40-0.98) and age-adjusted mortality from chronic obstructive lung
      disease (OR=0.50, CI=0.32-0.79), cancers (OR=0.53, CI=0.34-0.084), and
      intentional injury (OR=0.50, CI=0.38-0.92). CONCLUSIONS: Locally generated tax
      revenues used for the provision of healthcare services are consistently
      associated with improved health outcomes of major public health importance. The
      means by which this advantage is achieved will require additional research.

PMID- 17234487
TI  - Increasing physical activity among church members: community-based participatory
      research.
AB  - BACKGROUND: Faith-based interventions using a community-based participatory
      approach hold promise for eliminating ethnic health disparities. This study
      evaluated the effects of a volunteer-led statewide program to increase physical
      activity among members of African-American churches. METHODS: African Methodist
      Episcopal churches within six regions (Conferences) were randomly assigned to
      receive training in the program immediately or 1 year later. A cohort of 20
      randomly selected churches and 571 members within them took part in telephone
      surveys at baseline (May-September 2003) and 1 year (May-August 2004) and 2 years
      later (June-September 2005). Primary outcomes were physical activity
      participation, meeting physical activity recommendations, and stage of readiness
      for physical activity change. Statistical analyses were completed in April 2006.
      RESULTS: Volunteers (N=889) from 303 churches were trained. Among survey
      respondents, physical activity did not increase significantly over time, although
      67% were aware of the program. Program awareness was significantly related to all
      three physical activity outcomes and to fruit and vegetable consumption. Pastoral
      support was significantly associated with physical activity. CONCLUSIONS:
      Although this intervention reached a large number of churches and created
      awareness of intervention components, no effects on physical activity behaviors
      were found. Potential reasons for the lack of significant effects are discussed.

PMID- 17234488
TI  - Intimate partner violence and housing instability.
AB  - BACKGROUND: The mental and physical health consequences of intimate partner
      violence (IPV) have been well established, yet little is known about the impact
      of violence on a woman's ability to obtain and maintain housing. This cross
      sectional study examines the relationship between recent IPV and housing
      instability among a representative sample of California women. It is expected
      that women who have experienced IPV will be at increased risk for housing
      instability as evidenced by: (1) late rent or mortgage, (2) frequent moves
      because of difficulty obtaining affordable housing, and/or (3) without their own
      housing. METHODS: Data were taken from the 2003 California Women's Health Survey,
      a population-based, random-digit-dial, annual probability survey of adult
      California women (N=3619). Logistic regressions were used to predict housing
      instability in the past 12 months, adjusting for the following covariates; age,
      race/ethnicity, education, poverty status, marital status, children in the
      household, and past year IPV. RESULTS: In the multivariate model, age,
      race/ethnicity, marital status, poverty, and IPV were significant predictors of
      housing instability. After adjusting for all covariates, women who experienced
      IPV in the last year had almost four times the odds of reporting housing
      instability than women who did not experience IPV (adjusted odds ratio=3.98, 95%
      confidence interval: 2.94-5.39). CONCLUSIONS: This study found that IPV was
      associated with housing instability among California women. Future prospective
      studies are needed to learn more about the nature and direction of the
      relationship between IPV and housing instability and the possible associated
      negative health consequences.

PMID- 17234489
TI  - Trends in adolescent fruit and vegetable consumption, 1999-2004: project EAT.
AB  - BACKGROUND: Diets abundant in fruits and vegetables are associated with reduced
      risk for chronic disease, but intakes of adolescents are often inadequate. To
      design effective interventions it is important to understand how dietary intake
      changes longitudinally during adolescence and to monitor progress in the
      population toward fruit and vegetable consumption recommendations. The objective
      of this study was to examine longitudinal and secular trends in fruit and
      vegetable intake among two cohorts of Minnesota adolescents over the period 1999
      2004. METHODS: Measures of fruit and vegetable intake and demographics were
      completed by 944 boys and 1161 girls who were Project EAT participants in 1999
      and 2004. In 2005, mixed linear regression models were used to estimate (1)
      longitudinal trends among two cohorts of young people during developmental
      transitions and (2) age-matched secular trends between the two cohorts of young
      people at middle adolescence. RESULTS: Longitudinal trends indicated that
      adolescents decreased their daily intake of fruit and vegetables by an average of
      0.7 servings during the transition from early to middle adolescence and by 0.6
      servings from middle to late adolescence. Analyses of age-matched secular trends
      at middle adolescence showed a mean daily decrease of 0.7 servings among girls
      and 0.4 servings among boys between 1999 and 2004. CONCLUSIONS: The large
      longitudinal and secular declines in fruit and vegetable intakes of adolescents
      indicate a strong need for further research to understand why consumption is
      decreasing among adolescents and to develop more effective interventions for
      increasing fruit and vegetable consumption during this critical developmental
      period.

PMID- 17234490
TI  - Non-agricultural work injuries among youth: a systematic review.
AB  - BACKGROUND: To systematically review the quantitative literature on factors
      associated with youth non-agricultural work injury. METHODS: Seven electronic
      databases were searched for studies published between 1980 and 2005. In addition,
      reference lists from each potentially eligible study were checked and experts in
      the field contacted for additional studies. Studies had to meet relevance and
      quality appraisal criteria. RESULTS: Nine cross-sectional studies using
      multivariate analyses met the inclusion and quality appraisal criteria. This best
      evidence synthesis found that work injury varied significantly with job and
      workplace factors such as hazard exposure and perceived work overload. Visible
      minority status was also associated with likelihood of a work injury. The lack of
      youth work injury studies assessing the following factors was also identified:
      physical and cognitive development, safety training, supervision, social
      environment of the workplace, and intervention studies. CONCLUSIONS: This review
      has potential implications for prevention of work injuries. First, interventions
      need to target modifiable risk factors. This systematic review pointed to two
      job/workplace factors that are potentially modifiable: hazard exposure and work
      pace pressure. Second, the multiple determinants of work injury highlight the
      need to develop interventions and policies that focus on multiple factors rather
      than one-dimensional approaches that target a specific factor.

PMID- 17234491
TI  - Public health systems research: the new kid on the block.

PMID- 17234492
TI  - High-quality health care for children: what can we do?

PMID- 17234493
TI  - Metabolic control and nocturnal enuresis in children with type 1 diabetes.
AB  - This study examined the relationship between metabolic control and enuresis in
      youths with type 1 diabetes. Participants were 203 youths with type 1 diabetes at
      an outpatient pediatric diabetes clinic. Outcome measures included HbA(lc),
      nocturia, blood glucose, polydipsia, frequency of daytime urination, and diabetic
      ketoacidosis. The mean fasting blood glucose (FBG) level of children with
      enuresis (FBG = 192 mg/dl) was significantly higher than that of children without
      enuresis (FBG = 160 mg/dl, p = .03). Differences in HbA(lc) levels between
      children with enuresis and those without enuresis approached significance (9.2%
      vs. 8.6%, p = .07). Findings indicate that metabolic control indices (FBG,
      HbA(1c), polyuria, and polydipsia) are related to nocturnal enuresis in youths
      with type 1 diabetes. Further studies should determine the mechanism by which
      this relationship occurs to initiate appropriate interventions.

PMID- 17234494
TI  - Work environment perceptions of pediatric nurses.
AB  - This study assessed whether pediatric nurse perceptions of the work environment
      differed (1) from nurses employed in nonpediatric settings, (2) by the type of
      pediatric practice setting, or (3) by year of birth. The results of the study
      suggested that pediatric nurses had more positive perceptions of unit support,
      workload, and overall nurse satisfaction than their colleagues working in
      nonpediatric facilities. Specific to pediatrics, younger nurses and those working
      in critical care settings seemed to be the happiest with their work environment.

PMID- 17234495
TI  - Human figure drawings as a measure of children's emotional status: critical
      review for practice.
AB  - Human figure drawing is a common measurement that is used in practice and
      research. Drawing is a fun, inexpensive, and easy-to-administer method used to
      provide school-age children a projective means of expressing attitudes and
      emotions. As cognition matures, the content of drawing develops. The inclusion of
      emotional indicators in drawing signifies possible emotional problems. Recently,
      drawing has been used in countries and cultures other than the United States.
      Drawing can be implemented in any setting by all health care professionals.

PMID- 17234496
TI  - "Living with risk": mothering a child with food-induced anaphylaxis.
AB  - Food-induced anaphylaxis (FIA) affects an increasing number of children and
      families encountered in a variety of nursing environments. Sensitive nursing care
      requires consideration of the psychosocial impact of the condition. The purpose
      of this phenomenological study was to arrive at an understanding of the mother's
      lived experience of parenting a child with FIA. Semistructured interviews were
      conducted with six mothers of children 6 to 12 years old considered at risk for
      FIA. Data analysis was carried out concurrently with data collection, revealing
      "Living with Risk" as the essence of the experience, supported by five themes:
      "Living with Fear," "Worrying About Well-Being," "Looking for Control," "Relying
      on Resources," and "It Is Hard But It Is Not." These findings should assist
      nurses in meeting families' education and support needs related to FIA.

PMID- 17234497
TI  - Metabolic syndrome in a multiethnic sample of school children: implications for
      the pediatric nurse.
AB  - There is lack of translational work that may assist the pediatric nurse in
      identifying the child who is at risk for metabolic syndrome. Early identification
      of the syndrome could assist pediatric health care providers in intervening and
      in lowering child health risks. Fasting serum insulin, metabolic syndrome
      criteria, and dietary intake were examined in a multiethnic sample of children
      aged 9-15 years. Forty-seven percent had two or more risk factors for metabolic
      syndrome, and 28% had three or more risk factors. Insulin levels were negatively
      correlated with the recommended dietary allowance. A regression model, including
      gender, age, race, body mass index, serum glucose, high-density lipoprotein
      cholesterol, triglycerides, and blood pressure, explained 48% of insulin
      variance.

PMID- 17234498
TI  - Family influence on self-care, quality of life, and metabolic control in school
      age children and adolescents with type 1 diabetes.
AB  - This study explored the influence of family behaviors on self-care, quality of
      life (QoL), and metabolic control in school-age children and adolescents with
      type 1 diabetes. Ninety-nine participants were recruited in the midsouth from a
      health science center and an affiliated diabetes camp. Warm and caring family
      behaviors predicted self-care behaviors and aspects of QoL for the participants.
      African American school-age children and adolescents had more worries related to
      diabetes and had poorer metabolic control than Caucasians. Nursing implications
      included emphasizing open family communication and providing emotional support
      for diabetes management to promote developmentally appropriate levels of self
      care and QoL.

PMID- 17234499
TI  - Child health literacy.

PMID- 17234500
TI  - How physicians and nurses handle fear in children with cancer.
AB  - Previous research on fear in children with cancer has often focused on
      interventions to alleviate fear related to medical procedures and less on how to
      meet the challenges related to existential fear. This study aimed to describe how
      experienced nurses and physicians handle fear in children with cancer. Ten nurses
      and physicians with more than 10 years of experience in child oncology from a
      university hospital in Sweden were interviewed, and a qualitative content
      analysis was performed on the data. Nurses' and physicians' handling of fear
      encompasses commitment and closeness and yet also a distancing from fear and its
      expressions.

PMID- 17234501
TI  - Creating a safety culture at the Children's and Women's Health Centre of British
      Columbia.
AB  - The Children's' and Women's Health Centre of British Columbia (C&W) is the
      largest hospital providing specialized care to women and children across the
      province of British Columbia in Canada. The values of quality and safety are
      threaded throughout the C&W strategic plan which emphasizes that safety is vital
      for better health. At C&W, a multifaceted approach is used to create and sustain
      a culture of safety. The Institute for Healthcare Improvement (IHI) has developed
      tools to facilitate the development of safety cultures within hospital settings.
      This article describes the implementation of some of these tools, such as the
      Safety Briefings Model and Patient Safety Leadership Walkrounds. We will discuss
      how we adapted these strategies to our pediatric settings; what we learned
      through the implementation process-our successes and challenges; and implications
      for future success.

PMID- 17234502
TI  - Effect of increased vegetable and fruit consumption on plasma folate and
      homocysteine concentrations.
AB  - OBJECTIVE: We assessed the effects of an intervention aimed at increasing the
      consumption of fruits and vegetables on plasma folate and homocysteine
      concentrations. METHODS: Seventy-one healthy non-smoking women (mean +/- SD 41 +/
      4 y of age) were randomized to an intervention or a control group. Participants
      in the intervention group (n = 36) received weekly packets containing fruits and
      vegetables free of charge and were asked to consume a daily amount of >or=200 g
      of vegetables and two pieces of fruit (the Dutch recommended intake level) over a
      period of 1 mo. Control subjects did not receive any intervention. RESULTS:
      Compared with the control group, reported fruit and vegetable intakes in the
      intervention group increased by 133 g/d (95% confidence interval [CI] 87-179, P <
      0.001) for fruits and juice and 64 g/d (95% CI 37-91, P < 0.001) for vegetables
      and estimated folate intake from fruits and vegetables increased by 40 microg/d
      (95% CI 22-58, P < 0.001). However, no effect was observed on plasma folate
      concentrations (intervention effect 0.3 nmol/L, 95% CI -1.8 to 2.8, P = 0.77) or
      homocysteine concentrations (intervention effect 0.26 micromol/L, 95% CI -0.34 to
      0.87, P = 0.39). CONCLUSION: The results suggest that 4 wk of increased fruit and
      vegetable consumption to the recommended amounts may be insufficient to change
      plasma folate and homocysteine concentrations.

PMID- 17234503
TI  - Effects of high-fructose corn syrup and sucrose consumption on circulating
      glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women.
AB  - OBJECTIVE: Fructose has been implicated in obesity, partly due to lack of insulin
      mediated leptin stimulation and ghrelin suppression. Most work has examined
      effects of pure fructose, rather than high-fructose corn syrup (HFCS), the most
      commonly consumed form of fructose. This study examined effects of beverages
      sweetened with HFCS or sucrose (Suc), when consumed with mixed meals, on blood
      glucose, insulin, leptin, ghrelin, and appetite. METHODS: Thirty lean women were
      studied on two randomized 2-d visits during which HFCS- and Suc-sweetened
      beverages were consumed as 30% of energy on isocaloric diets during day 1 while
      blood was sampled. On day 2, food was eaten ad libitum. Subjects rated appetite
      at designated times throughout visits. RESULTS: No significant differences
      between the two sweeteners were seen in fasting plasma glucose, insulin, leptin,
      and ghrelin (P > 0.05). The within-day variation in all four items was not
      different between the two visits (P > 0.05). Net areas under the curve were
      similar for glucose, insulin, and leptin (P > 0.05). There were no differences in
      energy or macronutrient intake on day 2. The only appetite variable that differed
      between sweeteners was desire to eat, which had a higher area under the curve the
      day after Suc compared with HFCS. CONCLUSION: These short-term results suggest
      that, when fructose is consumed in the form of HFCS, the measured metabolic
      responses do not differ from Suc in lean women. Further research is required to
      examine appetite responses and to determine if these findings hold true for obese
      individuals, males, or longer periods.

PMID- 17234504
TI  - BCAA-enriched snack improves nutritional state of cirrhosis.
AB  - OBJECTIVE: A late evening snack improves the catabolic state in patients with
      advanced liver cirrhosis. We tested whether long-term (3 mo) late evening
      snacking that included a branched-chain amino acid (BCAA)-enriched nutrient
      mixture produces a better nutritional state and better quality of life than
      ordinary food in patients with hepatitis C virus-positive liver cirrhosis.
      METHODS: In a multicenter, randomized study, 48 patients with liver cirrhosis
      received late-evening supplementation with the BCAA-enriched nutrient mixture or
      ordinary food, such as a rice ball or bread, for 3 mo. During the study period,
      each patient was instructed on energy and protein intake. Blood biochemical data,
      nitrogen balance, respiratory quotient, and health-related quality of life (Short
      Form 36 questionnaire) were evaluated at baseline and at the end of the study.
      RESULTS: Total and late-evening energy intakes were similar in the two groups at
      3 mo. Serum albumin level, nitrogen balance, and respiratory quotient were
      significantly improved by the BCAA mixture but not by ordinary food. The
      parameters of the Short Form 36 did not statistically significantly improve over
      3 mo in either group. CONCLUSION: Long-term oral supplementation with a BCAA
      mixture is better than ordinary food in a late evening snack at improving the
      serum albumin level and the energy metabolism in patients with cirrhosis.

PMID- 17234505
TI  - Short-term effects of parenteral nutrition of cholestatic infants with lipid
      emulsions based on medium-chain and long-chain triacylglycerols.
AB  - OBJECTIVE: Infants with chronic cholestasis may require parenteral nutrition with
      lipid emulsions to provide energy and essential fatty acids but the optimal
      strategy is controversial. METHODS: We studied the effects of parenteral lipid
      emulsions with long-chain triacylglycerols (LCTs) or a mixture of LCTs and medium
      chain triacylglycerols (MCTs/LCTs) on serum bilirubin and lipid metabolism in
      cholestatic infants who received these 20% emulsions in alternating order for 3 d
      each, together with a glucose and amino acid infusion. RESULTS: Of 11 recruited
      infants, two dropped out because enteral feeding could be established. In nine
      infants (2-8 mo of age, mean age 4.2 mo) who completed the study, serum bilirubin
      decreased from baseline to 6 h after the end of LCT infusion (from 8.5 +/- 2.0 to
      7.8 +/- 1.8 mg/dL, mean +/- SEM, P < 0.05) and MCT/LCT infusion (7.9 +/- 6.5 to
      7.1 +/- 6.5 mg/dL, P < 0.05). Cholesterol, triacylglycerol, and phospholipid
      concentrations in plasma and in chylomicrons, very low-density lipoprotein, low
      density lipoprotein, and high-density lipoprotein were not changed by either
      emulsion. Total polyunsaturated fatty acid contents in high-density lipoprotein
      phospholipids increased during LCT infusion (from 29.8 +/- 0.9 to 35.9 +/- 1.4%
      wt/wt, P < 0.05) and MCT/LCT infusion (from 30.4 +/- 1.0 to 33.0 +/- 0.7%, P <
      0.05). The long-chain polyunsaturated fatty acid docosahexaenoic acid increased
      only with the LCT infusion. Because docosahexaenoic acid availability during
      infancy is important for early visual and cognitive development, the use of
      soybean oil-based lipid emulsions may be preferable for infants with severe
      progressive cholestasis. CONCLUSION: The MCT/LCT and LCT emulsions showed a good
      metabolic tolerance in infants with chronic cholestasis but had a differential
      effect on high-density lipoprotein phospholipid contents of arachidonic and
      docosahexaenoic acids.

PMID- 17234506
TI  - Effect of eicosapentaenoic/docosahexaenoic fatty acids and soluble fibers on
      blood lipids of individuals classified into different levels of lipidemia.
AB  - OBJECTIVE: This study evaluated the effect of a formulation containing
      eicosapentaenoic acid and docosahexaenoic acid combined with soluble fibers (beta
      glucan and guar gum) on fasting blood lipids used as coronary heart disease
      biomarkers of individuals classified into different levels of lipidemia by
      multivariate techniques. METHODS: Serum total cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerol,
      plasma glucose concentrations, body mass index, age, and waist circumference were
      determined in 99 healthy volunteers. Three clusters or subgroups were identified
      according to coronary heart disease risk levels. Within each cluster, individuals
      were randomly assigned to one of four experimental groups, with each group
      receiving samples of a functional formulation containing 460 mg of omega-3
      polyunsaturated fatty acids and/or 580 mg of soluble fibers, and placebo to be
      consumed in one bottle per day (200 mL) for 6 wk. RESULTS: No significant changes
      were observed for triacylglycerol (P = 0.281) and total cholesterol (P = 0.082)
      concentrations across the three subgroups. Soluble dietary fibers improved the
      sensory quality of the formulation containing eicosapentaenoic acid and
      docosahexaenoic acid. The efficiency of cluster analysis to discriminate
      individuals in subgroups was confirmed by one-way analysis of variance (P <
      0.003). CONCLUSION: The omega-3 polyunsaturated fatty acid supplementation
      equivalent to fish consumed 2.5 to 3 times per week by a functional food
      containing soluble dietary fiber showed no beneficial result in terms of changes
      in blood lipids in individuals classified according to different levels of
      lipidemia. Small numbers of patients in each cluster and possibly the low dose of
      fish oil and soluble dietary fibers used in this study may have also contributed
      to the lack of these differences. Multivariate techniques proved to be a very
      efficient tool to solve the heterogeneity problem usually observed in human
      designs and to evaluate the results within subgroups categorized by n variables
      extracted from the same population.

PMID- 17234507
TI  - Protective effects of D-glucaro 1,4-lactone against oxidative/nitrative
      modifications of plasma proteins.
AB  - OBJECTIVE: The protective effects of D-glucaro 1,4-lactone (1,4-GL) against
      oxidative/nitrative protein damage (determined by parameters such as levels of
      protein carbonyl groups and nitrotyrosine residues) to human plasma treated with
      peroxynitrite (ONOO-) or hydroperoxide (H2O2) were studied in vitro. We also
      investigated the effects of 1,4-GL on the level of total free thiol groups and
      low-molecular-weight thiols (glutathione and homocysteine) in plasma treated with
      ONOO- (0.1 mM). METHODS: Levels of carbonyl groups and nitrotyrosine residues in
      human plasma proteins were measured by ELISA and a competition ELISA,
      respectively. High-performance liquid chromatography (HPLC) was used to analyze
      free thiols from plasma. RESULTS: Exposure of plasma to ONOO- (0.1 mM) resulted
      in an increase of the level of carbonyl groups and nitrotyrosine residues in
      plasma proteins and in a distinct decrease in total thiols and low-molecular
      weight thiols (glutathione and homocysteine) measured by high-performance liquid
      chromatography. In the presence of 1,4-GL (0.4-6.4 mM), a distinct decrease in
      carbonyl group formation and tyrosine nitration in plasma proteins and changes in
      plasma thiols caused by 0.1 mM of peroxynitrite were observed. Moreover, 1,4-GL
      inhibited plasma protein oxidation induced by H2O2 (2 mM). CONCLUSION: The
      obtained results indicate that in vitro 1,4-GL has inhibitory effects on ONOO--
      or hydroperoxide-mediated oxidative stress in human plasma and changes plasma
      redox thiol status. The mechanism of the antioxidative action of 1,4-GL present
      in plasma is not known yet.

PMID- 17234508
TI  - Liver-protecting effects of table beet (Beta vulgaris var. rubra) during ischemia
      reperfusion.
AB  - OBJECTIVE: Table beet (Beta vulgaris var. rubra) contains important bioactive
      agents (betaine and polyphenols), which have a wide range of physiologic effects.
      Because nutritive antioxidants may reduce the occurrence of complications and
      postoperative mortality, dietary intake of polyphenols and vitamins before
      surgery may greatly contribute to the survival of patients. Our aim was to
      determine the liver-protecting properties of bioactive substances of table beet
      in a model of ischemia-reperfusion injury of the rat. METHODS: Wistar rats were
      divided into two groups: non-treated (n = 24) and fed with table beet (n = 8).
      For 10 days the second group was treated with lyophilized table beet (2 g/kg body
      weight daily) mixed into the rat chow. Hepatic ischemia was maintained for 45
      min, followed by 15 min of reperfusion. Ischemia-reperfusion was carried out on
      animals from both groups. Chemiluminescent intensity, H-donating ability,
      reducing power, free SH group concentration, Randox-total antioxidant status,
      glutathione peroxidase, and superoxide dismutase activities were determined by
      luminometry and spectrophotometry. Fatty acid (Shimadzu GC) and metal ion
      (inductively coupled plasma optical emission spectrometry) concentrations were
      observed in the liver. RESULTS: As a result of feeding, global parameters (H
      donating ability, reducing power, free SH group concentration) and enzymatic
      antioxidants (glutathione peroxidase and superoxide dismutase) of the liver were
      found to increase significantly, which indicated that the treatment had a
      positive effect on its redox state. The increase found in zinc and copper content
      may protect the hepatocytes against oxidative stress because these elements are
      required for the function of superoxide dismutase enzymes. In the table beet
      group the concentration of short-chain fatty acids decreased, whereas that of
      long-chain fatty acids increased. The changes in metal element and fatty acid
      concentrations confirmed that these elements have an essential function in
      cellular pathways. CONCLUSION: It may be stated that a natural antioxidant-rich
      diet has a positive effect on redox homeostasis during hepatic ischemia
      reperfusion.

PMID- 17234509
TI  - Effects of omega-3 fatty acids on leukocyte Th1/Th2 cytokine and integrin
      expression in rats with gut-derived sepsis.
AB  - OBJECTIVES: This study examined the effect of fish oil (FO)-enriched diets before
      and/or omega-3 fatty acid-containing total parenteral nutrition (TPN) after
      sepsis on the distribution of the T-lymphocyte subpopulation, intracellular
      cytokine, and intestinal immunity in rats with gut-derived sepsis. METHODS: Rats
      were assigned to a control or one of four experimental groups. The control group
      and groups 1 and 2 were fed a semipurified diet, and groups 3 and 4 received FO
      instead of 20% soybean oil. After feeding the diets for 10 d, sepsis was induced
      by cecal ligation and puncture (CLP) in the experimental groups, whereas a sham
      operation was performed in the control group. TPN was maintained for 3 d after
      the CLP or sham operation. The control group and groups 1 and 3 were infused with
      conventional TPN, whereas the TPN solution used for groups 2 and 4 were
      supplemented with FO. All rats were sacrificed 3 d after the operation to examine
      their immune responses. RESULTS: Plasma and intestinal immunoglobin A levels were
      higher in the FO-supplemented groups than in the control group and group 1.
      Lymphocyte interferon-gamma expression in groups 3 and 4 was significantly lower,
      whereas interleukin-4 expression was higher than those of the control group and
      groups 1 and 2. The splenocyte CD4 percentage in groups 3 and 4 and the CD4/CD8
      ratio in group 4 were significantly higher than those in group 1. CONCLUSION:
      These findings suggest that FO administration before and/or after CLP are not
      immunosuppressive. FO-enriched diets before or before and after CLP resulted in a
      T-helper type 2 response and enhanced immunoglobulin A secretion. In addition,
      the splenocyte CD4 levels and CD4/CD8 ratio were maintained in rats with gut
      derived sepsis.

PMID- 17234510
TI  - Neurologic events with a totally implantable left ventricular assist device:
      European LionHeart Clinical Utility Baseline Study (CUBS).
AB  - BACKGROUND: Neurologic events such as thromboembolic and hemorrhagic strokes are
      common complications of mechanical circulatory support. We report the neurologic
      events observed in patients treated for end-stage heart failure with the
      implantable, pulsatile LionHeart left ventricular assist device (LVAD). This sub
      study was part of the LionHeart European Clinical Utility Baseline Study (CUBS).
      METHODS: Twenty-three male patients were implanted with the LionHeart LVAD in a
      non-randomized, observational study. Neurologic events were classified into three
      categories: (1) transient ischemic attacks (TIAs); (2) strokes, including
      cerebrovascular accidents (CVAs) and intracranial bleeding (ICB); and (3)
      "other," including hypoperfusion, coma and brain death. Neurologic injuries were
      also categorized as transient/reversible or permanent/disabling. RESULTS:
      Thirteen of 23 patients (57%) had a total of 30 neurologic events. Eight patients
      (35%) had 18 TIAs. Eight patients (35%) also had a stroke, either CVA (n = 5,
      22%) or ICB (n = 3, 13%), and 5 of these patients (22%) also had 12 TIAs. Three
      patients (13%) had 4 "other" neurologic events. Ten patients (43%) had
      transient/reversible neurologic deficits and 10 (43%) had permanent/disabling
      events. One patient (4%) had intracranial bleeding as a primary cause of death
      (anti-coagulation-related hemorrhage). The combined incidence of neurologic
      events was 1.37 events/patient-year. The incidences of transient and permanent
      events were 0.91 and 0.46 event/patient-year, respectively. CONCLUSIONS:
      Neurologic events caused morbidity in the CUBS trial, with infrequent mortality.
      These results are similar to previous experiences with destination therapy and
      underscore the need for improvements in LVAD design, patient selection and
      patient management to reduce the incidence of neurologic events.

PMID- 17234511
TI  - Evaluation of the clinical effectiveness of the Ventricular Assist Device Program
      in the United Kingdom (EVAD UK).
AB  - BACKGROUND: The UK Government funds ventricular assist device (VAD) implantation
      as bridge to transplantation (BTT) at three centers. Results from this program
      have not been published. METHODS: All 70 VAD implants for BTT, 71 inotrope
      dependent and 179 non-VAD transplant candidates, accepted for transplantation
      between April 2002 and December 2004, were prospectively monitored for survival
      to transplantation, survival overall and quality of life. RESULTS: Of the 70 VAD
      patients, 31 (44%) survived to heart transplantation, 4 (6%) were bridged to
      recovery and 5 remained on support at the end of the study. Thirty patients (43%)
      died while on support. Overall survival from VAD implant was 52% at 1 year. Ten
      percent of non-VAD inotrope-dependent patients and 9% of routine transplant
      candidates died while on the waiting list. For transplant recipients, 12-month
      post-operative survival was 84%, 85% and 84%, respectively, for VAD, inotrope
      dependent and routine transplant candidates. VAD and non-VAD patients had similar
      post-transplant adverse event rates. CONCLUSIONS: There was a role for VAD bridge
      to transplant for selected patients in the UK, despite the availability of an
      effective urgent transplant list. VAD patients who underwent transplantation had
      survival rates similar to other transplant candidates.

PMID- 17234512
TI  - Determination of optimal duration of mechanical unloading for failing hearts to
      achieve bridge to recovery in a rat heterotopic heart transplantation model.
AB  - BACKGROUND: Mechanical unloading (MU) of a failing heart using a left ventricular
      assist device (LVAD) can lead to "bridge to recovery" in some patients. However,
      it is still unknown how to determine when to withdraw assistance. We sought to
      determine the optimal duration of MU by investigating its short- and long-term
      effects using a rat model of heterotopic heart transplantation. METHODS: Heart
      failure (HF) was induced in Lewis rats by ligating the left anterior descending
      artery. In the MU-HF groups, failing hearts were harvested and heterotopically
      transplanted. In the non-unloaded HF groups and the control group, hearts were
      not transplanted. After 2, 4 and 8 weeks, we evaluated papillary muscle function,
      histologic change and cardiac gene expression. Normal hearts served as the
      control group. RESULTS: In the MU-HF groups, papillary muscle function improved
      significantly in the early period of unloading. It peaked and normalized at 4
      weeks of unloading, but decreased to 50% the level of a normal heart at 8 weeks.
      In parallel with papillary muscle function, expression of brain natriuretic
      peptide (BNP) mRNA and SERCA2a mRNA normalized at 2 and 4 weeks of unloading,
      respectively, but deteriorated after 4 weeks. Cardiomyocyte hypertrophy was
      normalized at 2 weeks of unloading, but extended unloading induced cardiac
      atrophy. Myocardial fibrosis increased after unloading. CONCLUSIONS: Mechanical
      unloading of the failing heart can help normalize cardiac function, cardiomyocyte
      hypertrophy and cardiac gene expression for an optimal duration (<4 weeks), but
      this normalization deteriorates with prolonged support.

PMID- 17234513
TI  - Restless legs syndrome in lung transplant recipients.
AB  - BACKGROUND: Given the increased incidence of steroid-induced diabetes and drug
      induced anemia, renal dysfunction and neuropathy, we believed that lung
      transplant recipients would be at an increased risk of developing restless legs
      syndrome (RLS). We performed a cross-sectional, observational study to determine
      the prevalence and characteristics of RLS in this population. METHODS: Patients
      filled out two questionnaires during a routine visit: (1) a diagnostic tool for
      RLS, based on the core clinical features; and (2) a 10-question rating scale used
      to assess severity. Data were obtained by medical record review with regard to
      demographics, lung transplant characteristics and known risk factors for RLS.
      RESULTS: Forty-two lung transplant recipients (age 46.6 +/- 15.4 years [mean +/-
      SD]; 24 women, 18 men) without a family history of RLS were recruited. RLS was
      found in 47.6% (20 of 42) of the patients and 80% had moderate or severe RLS.
      Seventy-five percent of those with RLS were women (p = 0.03). RLS patients had a
      serum calcium level that was higher than those without RLS (p = 0.05) and were
      more likely to be recipient (p = 0.02) or donor positive (p = 0.07) for
      cytomegalovirus (CMV). All 4 hypothyroid patients on replacement therapy were in
      the RLS group. The prevalence of diabetes mellitus and chronic renal failure were
      not significantly different between the RLS and non-RLS groups. CONCLUSIONS:
      There was a very high prevalence of RLS in our lung transplant population and
      most patients had moderate or severe symptoms. RLS patients were more likely to
      be women, donor or recipient positive for CMV, hypothyroid, and to have an
      elevated serum calcium level.

PMID- 17234514
TI  - Influence of blood group on mortality and waiting time before heart
      transplantation in the United kingdom: implications for equity of access.
AB  - BACKGROUND: We examined waiting time for adult heart transplantation in the UK
      and sought to determine whether recipients with particular ABO blood groups were
      disadvantaged. METHODS: Data were obtained from the National Transplant Database.
      Registration outcome data were analyzed for 622 new, non-urgent, adult, heart
      only registrations from April 1, 1999 to March 31, 2003. Unadjusted waiting times
      of the 618 first registrations were summarized using Kaplan-Meier estimates.
      RESULTS: Death rates were relatively low, with no significant difference in the
      proportions of patients among the different blood groups who died while waiting.
      A smaller proportion of blood group O patients were transplanted at 1 year after
      registration, with a significant difference in waiting time to transplant between
      blood groups (p < 0.0001). Blood group A and AB patients were generally
      transplanted sooner than O and B patients, with median waiting times of 81 days
      (95% CI: 67 to 114) and 76 days (95% CI: 52 to 178) vs 214 days (95% CI: 162 to
      308) and 174 days (95% CI: 78 to 249), respectively. CONCLUSIONS: Although no
      particular blood group was disadvantaged in terms of mortality on the heart
      transplant list, blood group O and B patients waited significantly longer for
      transplantation. The difference was at least partly due to a large proportion of
      blood group O hearts being used for non-O patients. To address this imbalance,
      the UK Transplant Cardiothoracic Advisory Group (CTAG) changed the allocation
      protocol, so that "out-of-zone" offers of blood group O donors for non-urgent
      patients are now restricted to O and B recipients.

PMID- 17234515
TI  - Decorin-mediated transforming growth factor-beta inhibition ameliorates adverse
      cardiac remodeling.
AB  - BACKGROUND: Implantation of a left ventricular assist device (LVAD) has been
      shown to induce regression of fibrosis in patients with congestive heart failure
      (CHF) and improve myocardial function. The mechanism of reverse remodeling after
      mechanical circulatory support (MCS), however, has not been fully characterized.
      In this study we examined the anti-fibrotic effects of decorin, an extracellular
      matrix (ECM) proteoglycan, on the transforming growth factor-beta (TGF-beta)
      pathway. METHODS: Human myocardial tissue samples were obtained from patients
      undergoing LVAD implantation and again following subsequent transplantation after
      a sustained period of MCS. The specimens were examined by utilizing different
      molecular and histologic techniques, including human cardiac fibroblast in vitro
      studies. We assessed gene expression, mRNA and protein levels. RESULTS: We found
      a significant decrease in interstitial fibrosis after MCS, with a decrease in
      collagen mRNA transcription rates, serving as an indirect measurement of collagen
      synthesis. Both the mRNA and protein levels of decorin were significantly
      increased after a period of MCS. Decorin mRNA was up-regulated by 44% after MCS
      (p < 0.01), which paralleled the increase in interstitial decorin deposition (p <
      0.001). In addition, p-SMAD2, a molecular marker downstream of the TGF-beta
      pathway, was found to be inactivated after MCS (p < 0.02). Moreover, cultured
      human cardiac fibroblasts exposed to TGF-beta demonstrated decreased collagen
      production when exogenous decorin was added (p < 0.03). CONCLUSIONS: The decorin
      molecule is potentially involved in reverse cardiac remodeling, by directly
      inhibiting the TGF-beta pathway and its pro-fibrotic effects on the failing human
      heart.

PMID- 17234516
TI  - Human herpesvirus-6 and -7 after lung and heart-lung transplantation.
AB  - BACKGROUND: The impact of herpesvirus-6 and -7 (HHV-6, HHV-7) activation in lung
      transplant recipients is still poorly understood. We report the appearance of HHV
      6 and HHV-7 antigenemia after lung transplantation and evaluate the efficacy of
      anti-viral drugs against these viruses. METHODS: Twenty-two lung or heart-lung
      recipients were monitored for HHV-6, HHV-7 and cytomegalovirus (CMV) during 12
      post-operative months. HHV-6- and HHV-7-specific antigens and CMV pp65 antigens
      were analyzed in blood leukocytes and bronchoalveolar lavage fluid cells by
      monoclonal antibodies. Ganciclovir or valganciclovir prophylaxis for a minimum of
      3 months was given to 19 recipients at risk for CMV infection. RESULTS: HHV-6,
      HHV-7 and CMV antigenemia was detected in 20 (91%), 11 (50%) and 12 (55%)
      recipients (median 16, 31 and 165 days) after transplantation, respectively. HHV
      6 antigenemia occurred in 15 (79%), HHV-7 antigenemia in 7 (37%) and CMV
      antigenemia in 1 (7%) of these patients during anti-viral prophylaxis. HHV-6 or
      HHV-7 antigenemia was frequently associated with CMV antigenemia, which was
      detected 3 to 12 months after transplantation. Ganciclovir or valganciclovir
      treatment of CMV infection was effective against the concomitant HHV-6 and HHV-7
      antigenemia in 9 of 12 (75%) and 5 of 6 (83%) cases, respectively. One case of
      pneumonitis and 1 of encephalitis were temporally associated with HHV-6. No other
      clinical manifestations could be linked solely to HHV-6 or -7. CONCLUSIONS: HHV-6
      and -7 antigenemia was common and appeared early after lung transplantation. CMV
      prophylaxis was not able to prevent the appearance of HHV-6 and -7 antigenemia.

PMID- 17234517
TI  - Status of the endothelium-derived hyperpolarizing factor pathway in coronary
      arteries after heterotopic heart transplantation.
AB  - BACKGROUND: After the first year of transplantation, the major limitation to long
      term survival is the development of graft coronary vasculopathy, characterized by
      a pathologic activation of the endothelium with an attendant loss of its
      regulatory properties on homeostasis of the vascular wall. The present study was
      designed to evaluate the integrity of coronary vascular relaxations attributed to
      the endothelium-derived hyperpolarizing factor (EDHF) and to study
      hyperpolarization of smooth muscle cells after heterotopic heart transplantation.
      METHODS: Six weeks after heart transplantation in a porcine model, vascular
      reactivity studies of control, native and allograft epicardial coronary artery
      rings were performed in standard organ chamber experiments. Moreover, membrane
      potential measurements were made with intracellular microelectrodes in rings of
      native and allograft coronary arteries. RESULTS: There was a significant decrease
      in endothelium-dependent relaxations to 5-hydroxytryptamine (5-HT), high doses of
      bradykinin (BK) alone and BK plus N-omega-nitro-L-arginine (L-NNA) in rings from
      allograft compared to native, whereas the variation was significantly increased
      in response to cromakalim, a K(+)-ATP channel opener. Electrical and mechanical
      recordings showed no alteration in the resting membrane potential of smooth
      muscle cells, depolarization during contraction to prostaglandin F(2alpha)
      (PGF(2alpha)), or hyperpolarization in the presence of BK + L-NNA in rings of
      allograft vs native. CONCLUSIONS: In this swine model of heart transplantation,
      part of the reduction in endothelium-dependent relaxations to BK may be
      attributed to an alteration in the activity of EDHF. This impairment of EDHF
      mediated relaxations may compound the endothelial dysfunction preceding the
      development of coronary graft vasculopathy.

PMID- 17234518
TI  - Vascular remodeling 1 year after cardiac transplantation.
AB  - BACKGROUND: The belief that vascular remodeling and intimal hyperplasia are
      causes of luminal narrowing in cardiac allograft vasculopathy (CAV) is
      controversial. This study evaluated the relationship of vascular remodeling and
      intimal hyperplasia to luminal narrowing 1 year after orthotopic heart
      transplantation. METHODS: Intravascular ultrasound imaging was performed on 190
      cardiac transplant recipients at baseline and again 1 year after transplantation
      as part of a randomized trial of mycophenolate mofetil (MMF) and azathioprine
      (Aza). Studies 1 year apart were matched at 625 sites. All sites were classified
      into positive, non-significant and negative remodeling patterns, depending on a
      change of +/-10% in external elastic membrane area. Of the 190 patients, 99 were
      randomized to receive MMF, and 91 to receive Aza. RESULTS: A total of 625 sites
      were observed. Of these, 52% had no remodeling, 25% exhibited vessel dilation,
      and 23% had vessel shrinkage in the presence of variable intimal growth (Delta
      intimal area: 0.73 +/- 1.70 mm2, p < 0.0001; 1.23 +/- 2.02 mm2, p < 0.0001; and
      0.20 +/- 1.40 mm2, p = 0.09, respectively). Sixty percent of the lumen loss was
      due to a decrease in external elastic membrane area and 40% to an increase in
      intimal area (p = 0.005). Compared with Aza-treated patients, the MMF-treated
      patients had a lower incidence of vessel shrinkage (17% vs 28%, p = 0.001), and a
      trend for smaller maximum intimal thickness (0.21 +/- 0.25 mm vs 0.29 +/- 0.31
      mm, p = 0.052). CONCLUSIONS: Positive remodeling is associated with intimal
      growth, but negative remodeling does not correlate with any specific change in
      intimal hyperplasia. Constrictive remodeling is more responsible than intimal
      hyperplasia for the luminal narrowing that occurs. MMF is more efficacious than
      azathioprine in preventing the development of CAV at 1 year, by reducing the
      degree and incidence of vessel shrinkage and the progression of intimal
      hyperplasia.

PMID- 17234519
TI  - Sitaxsentan treatment for patients with pulmonary arterial hypertension
      discontinuing bosentan.
AB  - BACKGROUND: Bosentan, an oral ET(A)/ET(B) receptor antagonist, is approved for
      the treatment of pulmonary arterial hypertension (PAH). However, some patients
      discontinue bosentan because of hepatotoxicity or inadequate efficacy.
      Sitaxsentan, an oral, ET(A)-selective endothelin antagonist currently under
      investigation, may be an alternative treatment option. In this study we evaluate
      the safety and efficacy of sitaxsentan in patients discontinuing bosentan.
      METHODS: Forty-eight patients with idiopathic PAH or PAH associated with
      connective-tissue disease or congenital heart disease were randomized (double
      blind) to a single daily dose of either 50 mg or 100 mg sitaxsentan. Thirty-five
      of the 48 patients discontinued bosentan because of inadequate efficacy, as
      judged by the investigator, and 13 discontinued bosentan for safety concerns.
      Study end-points included change in 6-minute walk distance (6MWD), change in
      World Health Organization (WHO) functional class, time to clinical worsening, and
      change in Borg dyspnea score (Borg) from baseline to Week 12. RESULTS: With 100
      mg sitaxsentan, 5 of 15 patients (33%) who discontinued bosentan because
      inadequate efficacy improved, demonstrating a >15% increase in 6MWD, vs 2 of 20
      patients (10%) treated with 50 mg sitaxsentan. Fifteen percent and 20% of these
      patients had a >15% decrease in 6MWD in the 50- and 100-mg groups, respectively.
      Similar results were seen for the Borg and WHO functional class. Of the 12
      patients discontinuing bosentan because of hepatotoxicity, 1 developed elevated
      liver enzymes at 13 weeks of sitaxsentan therapy. Overall, sitaxsentan was well
      tolerated. CONCLUSIONS: Sitaxsentan may represent a safe and efficacious
      alternative endothelin receptor antagonist for patients discontinuing bosentan.

PMID- 17234520
TI  - FK778 in experimental xenotransplantation: a detailed analysis of drug efficacy.
AB  - BACKGROUND: This study examines the efficacy of FK778 regimens for prevention of
      different phases of xenograft rejection. METHODS: Antibody and complement tissue
      depositions were measured by immunofluorescence in a discordant ex vivo rat-to
      human heart perfusion model of hyperacute rejection with immunosuppressant
      enriched human blood. The concordant hamster-to-rat aortic xenotransplantation
      model was used to assess host cellular (lymphocyte activation, mixed lymphocyte
      reaction [MLR]) and humoral responsiveness (xenoantibody production) as well as
      histologic xenograft rejection. Recipients were treated for 14 days with FK778,
      tacrolimus, sirolimus or combination regimens at varying doses. RESULTS: Antibody
      binding during hyperacute rejection was unaffected by the immunosuppressive
      treatment, but complement deposition was reduced in the following order:
      tacrolimus > FK778 approximately sirolimus. FK778 most effectively reduced
      complement factor 5 in vitro. In untreated rats with hamster aortic xenografts, a
      large infiltrative response was observed within the grafts with extensive myocyte
      necrosis. Tacrolimus > FK778 approximately sirolimus dose-dependently diminished
      xenograft infiltration and in the same order reduced vessel-wall myocyte
      necrosis. Tacrolimus approximately FK778 > sirolimus reduced in vivo lymphocyte
      CD25 expression and tacrolimus > FK778 approximately sirolimus diminished MLR.
      Xenoreactive IgM and IgG antibody production levels were vigorously upregulated a
      few days after transplantation, but were significantly reduced by tacrolimus >
      FK778 approximately sirolimus. Combination regimens revealed no significant
      benefit when compared with the corresponding monotherapy groups. CONCLUSIONS:
      FK778 mildly interfered with hyperacute rejection and markedly suppressed acute
      humoral and cellular aortic xenograft rejection. However, T-cell-dependent host
      responses were most potently suppressed by tacrolimus, and the overall efficacy
      of FK778 was similar to that of sirolimus.

PMID- 17234521
TI  - Glucocorticoids alter the balance between pro- and anti-inflammatory mediators in
      the myocardium in a porcine model of brain death.
AB  - BACKGROUND: Cardiac dysfunction after brain death (BD) limits donors for cardiac
      transplantation. Glucocorticoids ameliorate brain death-induced donor heart
      dysfunction. We hypothesized that glucocorticoid therapy alleviates myocardial
      depression through altering the balance between pro- and anti-inflammatory
      mediators via the nuclear factor-kappaB (NF-kappaB)/inhibitor of kappaB-alpha
      (IkappaBalpha) pathway and/or by preserving beta-adrenergic receptor (betaAR)
      signaling in the heart. METHODS: Crossbred pigs (25 to 35 kg) were randomly
      assigned to the following groups (n = 5/treatment): sham (Group 1); BD (Group 2);
      and BD with glucocorticoids (30 mg/kg methylprednisolone), either 2 hours before
      (Group 3) or 1 hour after BD (Group 4). Tumor necrosis factor-alpha (TNF-alpha)
      levels were measured in plasma at baseline and 1 hour and 6 hours after BD.
      Protein levels were measured in left ventricular homogenates procured 6 hours
      after BD. RESULTS: Pro-inflammatory proteins (TNF-alpha) and interleukin-6 were
      lower in Group 3 and Group 4 compared with Group 2 at 6 hours after BD (p <
      0.01). Intracellular adhesion molecule-1 was also lower in Group 4 compared with
      Group 2 (p = 0.001). Interleukin-10, an anti-inflammatory mediator, was lower in
      Group 4 than in Group 2 (p < 0.001), but not different between Groups 2 and 3. At
      6 hours after BD, neither NF-kappaB activity nor basal adenylate cyclase activity
      differed between Groups 3 and 4 compared with Group 2. CONCLUSIONS:
      Glucocorticoids maintained myocardial function and shifted the balance of pro-
      and anti-inflammatory mediators after BD. The mechanisms by which glucocorticoids
      preserve myocardial function, however, do not appear to involve the NF-kappaB
      pathway or betaAR signaling.

PMID- 17234522
TI  - A wireless pressure sensor for monitoring pulmonary artery pressure in advanced
      heart failure: initial experience.
AB  - Hemodynamic goals have been used in the past to guide therapy in patients with
      heart failure (HF). For HF patients whose signs and symptoms of congestion do not
      resolve with initial therapy it appears reasonable to consider hemodynamic
      monitoring at experienced sites. It has been suggested that implantable
      hemodynamic sensors may enable frequent monitoring of hemodynamic changes in HF
      patients and be used in tailoring vasodilator. We present the first human case of
      radio-frequency based, wireless pressure sensor for the monitoring of pulmonary
      artery pressure in patients with advanced HF. This sensor is delivered into the
      pulmonary artery via percutaneous venous access.

PMID- 17234523
TI  - Late-onset tacrolimus-associated cerebellar atrophia in a heart transplant
      recipient.
AB  - Tacrolimus is a macrolide immunosuppressant frequently used after solid-organ
      transplantation. Moderate and severe neurologic side effects have been reported
      in patients receiving tacrolimus. Cerebral neurotoxicity is a rare but fatal
      calcineurin inhibitor-related complication, especially in kidney and liver
      transplant recipients. Often a reduction or a change in immunosuppressive regimen
      is the only means of clinical management. Herein we report a case of a 31-year
      old man who developed cerebellar atrophia while under immunosuppressive therapy 9
      years after heart transplantation. His neurologic constitution ameliorated after
      an immunosuppressant switch from tacrolimus to sirolimus.

PMID- 17234524
TI  - Pulmonary nocardiosis in a heart transplant patient: case report and review of
      the literature.
AB  - Pulmonary infection with Nocardia is an uncommon but serious infection found in
      immunocompromised patients. We describe a rapidly progressive pulmonary
      nocardiosis in a heart transplant patient. We then review the common clinical
      features of Nocardia infection in transplant recipients, outlining the challenges
      in its diagnosis and management. We also review the differences between
      Pneumocystis jiroveci prophylaxis regimens with respect to concomitant
      prophylaxis of Nocardia and other opportunistic infections.

PMID- 17234525
TI  - Management of multiple left ventricular assist device failures in a patient.
AB  - Device failure is a rare but life-threatening complication in patients receiving
      mechanical circulatory support. Because patients are supported by these devices
      for longer periods, the incidence of device failure has increased. We report 3
      instances of device failure and successful surgical management in a single
      patient.

PMID- 17234526
TI  - Large population sizes are a prerequisite for genetic association studies.

PMID- 17234527
TI  - Oral cancer screening aids: where is the science?

PMID- 17234528
TI  - A past medical history of gestational diabetes: its medical significance and its
      dental implications.
AB  - Approximately 7% of pregnant women develop gestational diabetes mellitus (GDM), a
      usually transient form of diabetes mellitus, because of the production of some
      placental and maternal adipose tissue elaborated hormones that alter glucose
      metabolism. In most women the disorder resolves at delivery, but within 10 years
      50% to 70% of these women go on to develop type 2 diabetes. The identification of
      women with past medical histories of GDM is a clinically useful marker for
      alerting the dentist to patients at heightened risk of occult type 2 diabetes,
      with a possible greater risk of developing periodontal disease and dental caries.
      Screening these patients for diabetes and establishing a preventative dental
      regimen may result in reducing the number of women with undiagnosed diabetes and
      diabetes-associated dental and cardiovascular diseases.

PMID- 17234529
TI  - Radiolucency in the anterior maxilla associated with an impacted tooth.

PMID- 17234530
TI  - Evaluation of upper lip hypoesthesia with a trigeminal somatosensory-evoked
      potential following Le Fort I osteotomy in combination with mandibular osteotomy.
AB  - PURPOSE: The purpose of this study was to objectively evaluate hypoesthesia of
      the upper lip following Le Fort I osteotomy in combination with mandibular
      osteotomy with trigeminal somatosensory evoked potential (TSEP). SUBJECTS AND
      METHODS: The subjects consisted of 25 patients with mandibular prognathism with
      maxillary retrognathism mandibular prognathism with or without asymmetry, who
      underwent Le Fort I osteotomy in combination with sagittal split ramus osteotomy
      (SSRO) or intraoral vertical ramus osteotomy (IVRO). Trigeminal nerve
      hypoesthesia at the region of the upper lip was assessed bilaterally by the TSEP
      method. The electrodes were placed exactly above the highest point of the
      vermilion border and on the mucosa of the upper lip. An electroencephalograph
      recording system (Neuropack Sigma; Nihon Koden Corp., Tokyo, Japan) was used to
      analyze the potentials. Each patient was evaluated preoperatively and then
      postoperatively at 1 week, 2 weeks, 1 month, 3 months, 6 months, and 1 year.
      RESULTS: The average measurable period and standard deviation of TSEP of the
      upper lip was 7.8 +/- 10.7 weeks following Le Fort I osteotomy, TSEP of the lower
      lip was 4.6 +/- 9.2 weeks in the patients who underwent SSRO with Le Fort I
      osteotomy, and 1.2 +/- 0.4 weeks in the patients who underwent IVRO with Le Fort
      I osteotomy. CONCLUSION: This study objectively proved that hypoesthesia could
      appear in the upper lips following Le Fort I osteotomy with TSEP. The measurable
      period for the upper lip following Le Fort I osteotomy tended to be longer than
      that for the lower lip in the patients who underwent SSRO and IVRO with Le Fort I
      osteotomy.

PMID- 17234531
TI  - Cranioplasty for midline metopic suture defects in adults with cleidocranial
      dysplasia.
AB  - OBJECTIVE: Patients with cleidocranial dysplasia often express concerns related
      to their perception of an undesirable esthetic appearance of their forehead and
      skull because of a combination of the persistence of metopic suture defects and
      frontal bossing. This case series reviews the use of a cranioplasty technique
      that has been developed to address such concerns. STUDY DESIGN: A series of 7
      adult patients with cleidocranial dysplasia were treated using a cranioplasty
      technique to correct visible metopic suture defects in the forehead region. The
      patients were 4 males and 3 females with a mean age of 29.0 years. All 7 patients
      underwent identical cranioplasty procedures. RESULTS: The metopic suture cranial
      defects were found to range in size from 0.6 to 2.4 cm in diameter and were
      present as full-thickness osseous defects in 4 of the 7 patients. All
      postoperative complications resolved spontaneously. Inpatient admission times
      ranged from 1 to 3 days. Follow-up ranged from 9 to 48 months with satisfactory
      subjective esthetic outcomes. The patients were content in all cases. CONCLUSION:
      This cranioplasty procedure successfully addresses the specific esthetic concerns
      of a rare and unique group of individuals. The procedure can be offered to
      cleidocranial dysplasia patients as part of their overall comprehensive
      craniomaxillofacial management.

PMID- 17234532
TI  - Maxillary sinus augmentation in the presence of antral pseudocyst: a clinical
      approach.
AB  - OBJECTIVE: The objective of this study is to present patients with sinus
      augmentation in the presence of an antral pseudocyst and the surgical procedure,
      complications, and outcome. STUDY DESIGN: From 2002 to 2005, 109 patients were
      scheduled for 1- or 2-stage maxillary sinus floor augmentation (n = 129) because
      of inadequate alveolar bone height for implant placement. Radiographically, a
      significant antral pseudocyst was shown. RESULTS: In 8 (7.3%) patients, an antral
      pseudocyst was diagnosed, and in 2 a history of inactive sinusitis was found
      preoperatively. A faint dome-shaped radiopacity was found at the lower border of
      the maxillary sinus. Average lesion size was 5.09 cm2. All implants functioned
      well at follow-up (mean 20 months). CONCLUSION: A pseudocyst of the maxillary
      sinus is not a contraindication for sinus augmentation. The low frequency of
      sinus membrane perforation and postsurgery sinusitis make the operation safe. In
      large lesions and in cases with an unclear diagnosis, further evaluation is
      needed before sinus augmentation.

PMID- 17234533
TI  - Superolateral dislocation of the intact mandibular condyle into the temporal
      fossa: review of the literature and report of a case.
AB  - Anterior dislocation of the mandibular condyle is common, but superolateral
      dislocation is quite rare. Because of its rarity, this type of dislocation is
      often misdiagnosed or completely overlooked. We describe an additional case of
      superolateral dislocation of the intact condyle into the temporal fossa. We
      review all of the available English literature on superolateral dislocation and
      discuss a causative mechanism, the diagnostic features, and clinical management.

PMID- 17234534
TI  - Extensive ameloblastoma of the jaws: surgical management and immediate
      reconstruction using microvascular flaps.
AB  - OBJECTIVE: Ameloblastoma is a rare histological benign but locally aggressive
      tumor with a marked tendency for recurrence. Especially larger, aggressive
      lesions require a more radical surgical approach resulting in large jaw defects.
      The purpose of this study is to analyze the long-term functional and esthetic
      results after immediate reconstruction of large jaw defects using microvascular
      flaps. STUDY DESIGN: A review of 7 cases of giant ameloblastoma (2 in the
      maxillary and 5 in the mandibular region) is presented. The lesions were between
      4 and 8 cm in diameter. All patients were treated by a radical surgical protocol.
      All cases were immediately reconstructed using microvascular grafts from either
      the scapula or the iliac crest bone. Dental implants were inserted in all
      patients after removal of the osteosynthesis material. RESULTS: All patients were
      prosthetically rehabilitated. All implants survived throughout the observation
      time. The esthetic and functional outcomes were satisfying in all patients. No
      case of recurrence of the tumor could be observed so far. CONCLUSION: According
      to our opinion, immediate reconstruction is the treatment of choice after radical
      surgical excision of ameloblastoma. This 1-step procedure decreases the number of
      surgeries and allows earlier prosthetic rehabilitation.

PMID- 17234535
TI  - Methemoglobinemia--an unusual cause of intraoperative hypoxia.

PMID- 17234536
TI  - Vascular malformation of the temporomandibular joint: report of a case and review
      of the literature.
AB  - The diagnosis and treatment of vascular anomalies is extremely challenging
      because of inconsistent terminology and classification systems, as well as
      nonspecific clinical and radiological findings. We report a vascular malformation
      that was treated successfully via resection, and reconstructed using a custom
      made temporomandibular joint fossa and condylar prosthesis by TMJ Concepts. The
      available pertinent literature is also reviewed.

PMID- 17234537
TI  - Efficacy of lycopene in the management of oral submucous fibrosis.
AB  - OBJECTIVES: To evaluate the efficacy of oral lycopene therapy in patients with
      oral submucous fibrosis and to compare these effects with a placebo. STUDY
      DESIGN: Fifty-eight patients with oral submucous fibrosis formed the population
      for the study and were randomly divided into 3 groups, evaluated weekly over a 2
      month period. Patients of group A (n = 21) received 16 mg of lycopene, those of
      group B (n = 19) received 16 mg of lycopene along with biweekly intralesional
      steroid injections, and those of group C (n = 18) were given a placebo. Paired
      and unpaired t tests were used for statistical evaluation. RESULTS: Mouth-opening
      values for the patients showed an average increase of 3.4 mm, 4.6 mm, and 0.0 mm
      for patients in groups A, B, and C, respectively. These values were statistically
      found to be highly significant. CONCLUSIONS: The observed effects suggest that
      lycopene can and should be used as a first line of therapy in the initial
      management of oral submucous fibrosis.

PMID- 17234538
TI  - Efficacy of oral lycopene in the management of oral submucous fibrosis.

PMID- 17234539
TI  - Impact of dry mouth and hyposalivation on oral health-related quality of life of
      elderly Japanese.
AB  - OBJECTIVE: To determine the association of hyposalivation and the perception of
      dry mouth with oral health-related quality of life for independently living
      elderly. STUDY DESIGN: The study sample consisted of 287 participants (mean age,
      66.1 years) at a Senior Citizen educational system. Stimulated salivary flow
      rates during chewing were measured. The OHIP-14 to measure the impact of oral
      conditions on health-related quality of life was used, and summary OHIP-14 scores
      combining the response codes for the 14 items were analyzed. RESULTS: A logistic
      regression analysis showed that a higher OHIP-14 score indicating a poorer
      quality of life was related to fewer residual teeth, perception of dry mouth on
      eating (OR: 4.01, P = .012) and hyposalivation (OR: 2.71, P = .006). CONCLUSION:
      It is suggested that both dry mouth and hyposalivation are important problems
      influencing the quality of life in independently living, relatively healthy
      elderly Japanese.

PMID- 17234540
TI  - The effects of xerogenic medications on oral mucosa among the Veterans Dental
      Study participants.
AB  - OBJECTIVES: To examine the association of xerogenic medications with the oral
      mucosa inflammation score (OMS) in US male veterans. METHODS: The relationship of
      having the worst 25th percentile in OMS and intake of xerogenic medications with
      different pharmacologic indications was analyzed by logistic regression,
      controlling for age in 3 categories (< or =44, 45-64, > or =65), smoking, disease
      burden index, alcohol abuse, and the duration of medication, in 290 subjects
      participating in the Veterans Dental Study. RESULTS: When polypharmacy and
      denture-wearing status in addition to the aforementioned covariates were
      controlled, the odds ratios for cardiovascular disease medications and
      sympathetic agonists were 2.82 (95% confidence interval [CI] 1.35-5.91, P <
      .006), and 2.96 (CI 1.21-7.26, P < .02), respectively, and those for
      psychotropics and antihistamines were 2.12 (CI 0.94-4.80, P < .06) and 2.09 (CI
      0.80-5.48, P < 0.14), respectively. CONCLUSION: Xerogenic medication may be
      associated with oral mucosal pathology.

PMID- 17234541
TI  - Cell-surface density of complement restriction factors (CD46, CD55, and CD59):
      oral squamous cell carcinoma versus other solid tumors.
AB  - OBJECTIVE: Complement restriction factors (CD46, membrane cofactor; CD55, decay
      accelerating factor; and CD59, protectin) are overexpressed on tumor cells, and
      they enable tumor cells to escape from complement-dependent and antibody-mediated
      killing. Cell-surface density of complement restriction factors (CRFs) on oral
      squamous cell carcinoma (OSCC) is compared with that found on other solid tumors
      (breast, pancreas, colon carcinomas, and melanoma) to understand the significance
      of their diversity. STUDY DESIGN: The cell-surface expression of CRFs on tumor
      cells was confirmed with confocal laser scan fluorescent microscopy. Cell
      suspension enzyme-linked immunosorbent assay (cs-ELISA), which measures the
      density of cell-surface antigens, was utilized to study CRFs on the cell surface
      of tumor cells (OSCC, 2 cell lines; breast, 5 cell lines; pancreas, 3 cell lines;
      colon, 3 cell lines; and melanoma, 9 cell lines). RESULTS: Confocal laser scan
      fluorescent microscopy confirmed the expression of CD46, CD55, and CD59 on the
      cell surface of OSCC cell lines SCC12 and SCC71. The relative densities of cell
      surface expression obtained from cs-ELISAs of CRFs on OSCCs are as follows: CD59
      > CD55 > CD46. The relative densities of the 3 CRFs in breast and pancreatic
      carcinomas were similar to those found in OSCCs, whereas the profile of CRFs in
      melanoma (CD59 > CD55 < CD46) and colon cancer (CD46 > CD55 > CD59) were
      different. CONCLUSIONS: These findings indicate diverse strategies adopted by
      tumor types to resist antibody-mediated complement-dependent cytotoxicity;
      possibly the factors (exogenous and endogenous) in their respective
      microenvironments may play a role in the diversity.

PMID- 17234542
TI  - Epidermal growth factor receptor distribution in pericoronal follicles:
      relationship with the origin of odontogenic cysts and tumors.
AB  - OBJECTIVE: Investigate the distribution of epidermal growth factor receptor
      (EGFR) in pericoronal follicles as a predictor of progression to odontogenic
      cysts and tumors. STUDY DESIGN: Immunohistochemical EGFR staining patterns
      (membrane-only, cytoplasm-only, or combined membrane and cytoplasmic staining) in
      the reduced enamel epithelium and nests of odontogenic epithelium associated with
      follicles of impacted molar teeth were evaluated. The staining pattern of 20
      specimens of pericoronal follicle was compared with that of 16 normal oral mucosa
      samples and to squamous cell carcinoma samples. RESULTS: Combined membrane and
      cytoplasmic staining was observed for normal oral mucosa mostly in proliferating
      layers (basal and suprabasal), decreasing in intensity toward the surface. Seven
      epithelial nests presented membrane-only staining, and the majority presented
      either a cytoplasm-only or a combined staining pattern. The staining patterns
      observed in reduced enamel epithelium were cytoplasm-only and combined.
      CONCLUSION: EGFR membrane-only staining may be an indicator of increased
      potential for epithelial nests to become odontogenic cysts or tumors.

PMID- 17234543
TI  - Low-grade central osteosarcoma of the mandible: a case study report.
AB  - Low-grade central osteosarcoma is a rare type of osteosarcoma with peculiar
      clinical radiographic and microscopic features. The aim of this article is to
      report and discuss a case of low-grade central osteosarcoma in the mandible of a
      42-year-old woman. The patient reported sensing mild pain and tooth mobility for
      a period of 4 years, despite continuous dental treatment. Radiographic evaluation
      showed a mixed radiopaque/radiolucenct lesion in the body, ramus, coronoid
      process, and condyle of the left side of the mandible. Destruction of the
      mandibular cortex in the area was also observed. After incisional biopsy, the
      patient underwent hemimandibulectomy. Microscopic findings showed a tumor
      exhibiting spindle cells with nuclear hyperchromasia and no mitotic activity,
      irregular osteoid formation, and soft tissue infiltration. The
      immunohistochemical analysis of the expression of Ki-67, Cyclin B1, and PCNA
      proteins (cellular proliferation markers) revealed a very low Ki-67+ and Cyclin
      B1+ cell index (mean 7% and 3%, respectively), but a moderate number of PCNA+
      cells (mean 49%). The 2 years of clinical and imaging postoperative follow-up
      showed no evidence of recurrence. Clinicians should be aware of these lesions,
      because histopathologicially low-grade central osteosarcoma may be misinterpreted
      as fibrous dysplasia.

PMID- 17234544
TI  - A comparative study of cone-beam computed tomography and conventional panoramic
      radiography in assessing the topographic relationship between the mandibular
      canal and impacted third molars.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of cone-beam CT compared with
      panoramic images in predicting neurovascular bundle exposure during extraction of
      impacted mandibular third molars. STUDY DESIGN: Cone-beam CT and panoramic images
      of 142 impacted mandibular third molars were prospectively evaluated to assess
      tooth relationship to the mandibular canal. These interpretations were then
      correlated with intraoperative findings. The sensitivity and specificity of the 2
      modalities in predicting neurovascular bundle exposure at extraction were
      calculated and compared. The diagnostic criterion for panoramic images was
      defined using multivariate logistic regression analysis. RESULTS: In predicting
      the exposure, the sensitivity and specificity were 93% and 77% for cone-beam CT,
      and 70% and 63% for panoramic images, respectively. Cone-beam CT was
      significantly superior to panoramic images in both sensitivity and specificity.
      CONCLUSION: Cone-beam CT was significantly superior to panoramic images in
      predicting neurovascular bundle exposure during extraction of impacted mandibular
      third molar teeth.

PMID- 17234545
TI  - Visualization of anterior disc displacement in temporomandibular disorders on
      contrast-enhanced magnetic resonance imaging: comparison with T2-weighted, proton
      density-weighted, and precontrast T1-weighted imaging.
AB  - OBJECTIVE: To compare postcontrast T1-weighted imaging (T1WI+) with precontrast
      T1-weighted (T1WI-), T2-weighted (T2WI), and proton density-weighted imaging
      (ProWI) in depiction of the anterior disc displacement (ADD) in temporomandibular
      disorders (TMDs). STUDY DESIGN: A total of 120 joints with TMD were included in
      this study. Qualitatively, Receiver operating characteristic analysis was
      performed. Quantitatively, the ratio of the intensity in the retrodiscal tissue
      to intensity in the disc (intensity ratio) was measured. RESULTS: One reader
      achieved superior performance in visualization of ADD with T1WI+ than with the
      other sequences. The other reader showed superiority with T1WI+ rather than T2WI
      or T1WI-. The intensity ratio on T1WI+ was significantly higher than the
      intensity ratio on other sequences. On T1WI,+ the intensity ratio in the joints
      with ADD was significantly higher than that in the joints without ADD.
      CONCLUSION: Postcontrast T1-weighted imaging can improve the visualization of ADD
      in TMDs.

PMID- 17234547
TI  - Influence of resin-based adhesive root canal fillings on the resistance to
      fracture of endodontically treated roots: an in vitro preliminary study.
AB  - OBJECTIVE: The aim was to investigate the root reinforcing capability of the
      resin-based RealSeal. STUDY DESIGN: In two groups (n=36) canals were instrumented
      with nickel-titanium rotary GTfiles or with hand K-files. Twelve teeth from each
      group were obturated with lateral compaction using either gutta-percha and AHPlus
      or RealSeal. The canals of twelve teeth of both groups were instrumented but not
      filled. Group 3 (n=12) acted as uninstrumented controls. The force required to
      fracture the roots was measured. ANOVA and Scheffe test were used for statistical
      analysis. RESULTS: The intact roots were significantly stronger than both groups
      with instrumented and unobturated roots (P<.05). Between the roots of both groups
      obturated with RealSeal and the intact roots there were no significant
      differences (P>.05). The roots obturated with RealSeal were significantly
      stronger than those obturated with gutta-percha and AHPlus (P<.05). CONCLUSIONS:
      An obturation with RealSeal significantly increases the fracture resistance of
      instrumented roots.

PMID- 17234546
TI  - Correlation of tuned aperture computed tomography with conventional computed
      tomography for evaluation of osseous healing in calvarial defects.
AB  - OBJECTIVE: To compare the diagnostic efficacy of iteratively restored tuned
      aperture computed tomography (TACT) with conventional computed tomography (CT)
      for evaluation of osseous healing in induced calvarial defects. STUDY DESIGN:
      Fifty-six calvarial defects in 14 rabbits received 1 of 4 possible treatments:
      copolymer membranes with and without bone marrow stromal cells (BMSCs), BMSCs
      alone, or no treatment (control). Healing was measured after 2, 4, and 8 wks as
      remaining defect areas measured on TACT and CT images. Histomorphometric analyses
      were done on the specimens. RESULTS: Bone formation was minimal to none in
      control defects and those treated with BMSCs or polymer matrices alone. Healthy
      bone formation was noted in defects treated with polymers impregnated with BMSCs.
      Unresolved defect area measurements using TACT and CT of osseous healing showed a
      high positive correlation. CONCLUSIONS: Potential for TACT to accurately detect
      osseous healing in surgical defects was demonstrated. High resolution of TACT
      combined with generation of information in 3D yields comparable performance to
      CT.

PMID- 17234548
TI  - Effect of various digital processing algorithms on the measurement accuracy of
      endodontic file length.
AB  - OBJECTIVE: The aim of this study was to compare the accuracy of endodontic file
      lengths after application of various image enhancement modalities. STUDY DESIGN:
      Endodontic files of three different ISO sizes were inserted in 20 single-rooted
      extracted permanent mandibular premolar teeth and standardized images were
      obtained. Original digital images were then enhanced using five processing
      algorithms. Six evaluators measured the length of each file on each image. The
      measurements from each processing algorithm and each file size were compared
      using repeated measures ANOVA and Bonferroni tests (P = 0.05). Paired t test was
      performed to compare the measurements with the true lengths of the files (P =
      0.05). RESULTS: All of the processing algorithms provided significantly shorter
      measurements than the true length of each file size (P < 0.05). The threshold
      enhancement modality produced significantly higher mean error values (P < 0.05),
      while there was no significant difference among the other enhancement modalities
      (P > 0.05). Decrease in mean error value was observed with increasing file size
      (P < 0.05). CONCLUSIONS: Invert, contrast/brightness and edge enhancement
      algorithms may be recommended for accurate file length measurements when
      utilizing storage phosphor plates.

PMID- 17234549
TI  - Detection of Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella
      intermedia, and Prevotella nigrescens in chronic endodontic infection.
AB  - Black-pigmented anaerobic rods such as Prevotella spp. and Porphyromonas spp. are
      involved in the etiology and perpetuation of endodontic infections. The aim of
      this study was to evaluate the prevalence of these species in chronic endodontic
      infections by using culture and polymerase chain reaction (PCR) techniques.
      Samples of 100 patients with root canals displaying chronic endodontic infections
      were obtained by sterilized paper points. Bacterial identification was performed
      by using culture and PCR techniques. By culture, in 33% of the samples, P.
      intermedia-P. nigrescens (75.8%), P. gingivalis (27.3%), and P. endodontalis
      (9.1%) were identified, and by PCR 60% of the samples harbored P. nigrescens
      (43.3%), P. gingivalis (43.3%), P. intermedia (31.7%), and P. endodontalis
      (23.3%). The presence of these black-pigmented anaerobic rods alone or in
      association in chronic endodontic infections seems to be frequent. PCR is a very
      sensitive technique for detecting DNA from bacterial cells. Culturing is only
      able to reveal living bacteria and is less sensitive for the identification of
      low numbers of bacterial cells.

PMID- 17234550
TI  - Influence of reduced air pressure methods on dye penetration in standardized
      voids.
AB  - OBJECTIVE: The objective of this study was to evaluate the influence of the
      moment when reduced pressure is applied on dye penetration patterns. STUDY
      DESIGN: Nine hundred and sixty glass capillary tubes of different inner diameter
      (0.3 mm and 0.8 mm), divided into 48 groups, were submerged into dye in 3
      different positions (horizontally, opening upwards, and opening downwards) under
      different vacuum conditions (passive, 5 kPa, 35 kPa, 70 kPa reduced pressure).
      When reduced pressure was applied half of the groups were submerged into dye
      before and half of the groups after the application of reduced pressure. Linear
      dye penetration was measured. Univariate analysis was performed with Mann-Whitney
      U test and Kruskal-Wallis test to select variables to be included in the
      regression model. A multiple logistic regression analysis with backward
      elimination was performed to assess the influence of different covariates on
      linear dye penetration. RESULTS: The multivariate linear regression showed that
      the moment of vacuuming had the greatest positive effect on linear dye
      penetration value (beta = 10.6, P < .0001). Also the level of pressure reduction
      had a positive effect on the outcome variable (beta = 0.2, P < .0001) while the
      vertical positioning of the tubes has negatively affected the outcome variable
      both for the open end upside (beta = -1.01, P = .024) and the open end downside
      (beta = -1.05, P = .019). Diameter of the tubes (P = .442) and immersion time (P
      = .727) had no effect on the outcome of linear dye penetration. CONCLUSIONS: Even
      minimum air pressure reduction applied before immersion of the specimens allowed
      the dye to extensively penetrate the voids.

PMID- 17234551
TI  - Colonic bleeding and a displaced biliary stent.

PMID- 17234552
TI  - Gastric metastases from anaplastic pancreatic cancer.

PMID- 17234553
TI  - Diverticular disease-associated segmental colitis.
AB  - Diverticular disease-associated segmental colitis is a unique variant of chronic
      colitis limited to segments of the left colon that harbor diverticula.
      Histologically, this disease mimics chronic idiopathic inflammatory bowel disease
      and can be indistinguishable from ulcerative colitis or Crohn's colitis on
      histologic grounds alone. Patients typically present with hematochezia and
      cramping abdominal pain, and colonoscopic evaluation reveals inflammatory changes
      limited to the segment of bowel containing the diverticula, with rectal sparing.
      Although this disease does not appear to be an unusual form of diverticulitis but
      possibly an immunologically mediated process, many patients respond to treatment
      directed toward diverticulitis. A subset of patients requires immunosuppressive
      therapy and/or surgery, and a small subset progresses to develop classic
      ulcerative colitis. Because of the histologic overlap with ulcerative colitis and
      occasionally Crohn's colitis, it is essential that endoscopists provide a full
      description of the macroscopic appearance of the inflammatory changes at
      endoscopy, such as limitation to a segment of diverticular disease, so that the
      pathologist can provide a more informative interpretation of the biopsy.

PMID- 17234554
TI  - Primary sclerosing cholangitis: patients with a rising alkaline phosphatase at
      annual follow-up.

PMID- 17234555
TI  - Diurnal variation in the chemical clearance of acid gastroesophageal reflux in
      infants.
AB  - BACKGROUND & AIMS: Clearance of acid gastroesophageal reflux is biphasic. During
      volume clearance, refluxed material is cleared from the esophagus by peristalsis,
      and during chemical clearance, acidified esophageal mucosa is neutralized by
      saliva and possibly secretions from the esophageal lumen. In this study, we
      examined the effects of feeding on the durations of volume clearance and chemical
      clearance. METHODS: Combined pH/multichannel intraluminal impedance tracings from
      12 symptomatic infants (median age, 20 weeks) were analyzed. Acid
      gastroesophageal reflux episodes having both volume clearance and chemical
      clearance components were grouped into 1 of 4 feeding cycle phases (feeding,
      first hour postprandial, second hour postprandial, and fasting). RESULTS: Mean
      duration of volume clearance and chemical clearance was 7.0 +/- 2.3 and 36.3 +/-
      8.5 minutes (P = .001), respectively, per patient and 24.7 +/- 2.7 and 127.5 +/-
      10.7 seconds (P < .0001), respectively, per episode. Whereas volume clearance did
      not change throughout the feeding cycle, chemical clearance was significantly
      prolonged during fasting (132.2 +/- 18.4 seconds) compared with feeding (13.5 +/-
      4.1 seconds, P = .0046) and 1st postprandial (64.0 +/- 19.4 seconds, P = .0333).
      Statistical analysis failed to demonstrate a significant relationship between
      nadir pH and chemical clearance (P = .3104) or between chemical clearance and the
      interaction between nadir pH and feeding cycle. CONCLUSIONS: Chemical clearance
      is significantly prolonged during fasting in infants. Falling pH alone cannot
      explain declining chemical clearance efficiency during later postprandial
      periods. We speculate that inefficient chemical clearance during fasting is
      likely due to reduced efficiency of acid clearance mechanisms that could include
      salivation, swallowing, peristalsis, and/or intraluminal secretion.

PMID- 17234556
TI  - The iceberg of celiac disease: what is below the waterline?
AB  - BACKGROUND & AIMS: We explored the relationships between anti-tissue
      transglutaminase antibody and indirect measures of malabsorption and disease
      activity in people with undetected celiac disease. METHODS: From the Cambridge
      General Practice Health Study, 7550 participants' serum samples were tested for
      antiendomysial antibody (EMA). The 87 samples positive for EMA were tested for
      human anti-tissue transglutaminase antibody (TGA). Multivariate linear regression
      was used to explore the relationship between TGA concentrations and various
      physiologic and anthropometric measures. RESULTS: Among the 87 EMA-positive
      people, there were consistent relationships between increasing TGA levels and
      various physiologic and anthropometric measures. A 50% increase in the mean TGA
      level was associated with a 0.02 g/cm2 (95% confidence interval [CI], -0.03 to 
      0.009) lower mean hip bone mineral density, a 0.1 g/dL (95% CI, -0.17 to -0.01)
      lower mean hemoglobin, a 0.22 kg/m2 (95% CI, -0.46 to 0.03) lower mean body mass
      index, a 0.09 mmol/L (95% CI, -0.16 to -0.02) lower serum cholesterol, and a 0.1
      mmol/L (95% CI, 0.04 to 0.16) higher random blood glucose concentration,
      independent of age, sex, and smoking habit. CONCLUSIONS: The relationships we
      found between concentrations of TGA and various physiologic and anthropometric
      variables suggest that in reality, celiac disease is a continuum with a variable
      degree of severity. Although clinically overt disease is defined by symptoms,
      signs, and small bowel histology, the severity of previously undetected disease
      variously labeled in the past as silent, potential, or latent could, instead, be
      estimated by the concentration of a detectable serum antibody.

PMID- 17234557
TI  - Sexual function in persons with inflammatory bowel disease: a survey with matched
      controls.
AB  - BACKGROUND & AIMS: Sexual problems as a result of inflammatory bowel diseases
      (IBDs) play an important role in patients' worries and concerns. We aimed to
      evaluate sexual function in men and women with IBD relative to healthy controls.
      METHODS: A random sample of the national patients organization was surveyed (n =
      1000). Age- and sex-matched friends were used as controls; in addition, controls
      were selected from a large health insurance cohort. Sexual function was evaluated
      using the Erectile Index of Erectile Function, and the Brief Index of Sexual
      Function in Women; impaired function was defined as a score less than -1 on a z
      normalized scale. The results are reported as age-adjusted odds ratios with 95%
      confidence intervals based on conditional logistic regression. RESULTS: The
      response rate was 41% in cases. Overall, 153 male and 181 female matched pairs
      were available for analysis. The proportion of patients who were married, had a
      partner, and were sexually active were similar between cases and controls.
      Depression was the most important determinant of impaired sexual function. Men
      with IBD in remission or mild activity had similar Erectile Index of Erectile
      Function scores as compared with controls. Comorbidity and antihypertensive
      therapy impacted on single subscores. Women with IBD showed impaired function
      irrespective of disease activity as compared with healthy controls. Results in
      women varied by type of control. High socioeconomic status was a protective
      factor for several subscores in women. CONCLUSIONS: Depression is the most
      important determinant of low sexual function.

PMID- 17234558
TI  - Effect of once- or twice-daily MMX mesalamine (SPD476) for the induction of
      remission of mild to moderately active ulcerative colitis.
AB  - BACKGROUND & AIMS: SPD476 (MMX mesalamine), a novel, once-daily mesalamine
      formulation, uses MMX Multi Matrix System (MMX) technology to delay and extend
      delivery of active drug throughout the colon. We performed a randomized, double
      blind, parallel-group, placebo-controlled, multicenter phase III study in
      patients with mild to moderately active ulcerative colitis. METHODS: Two hundred
      eighty patients with mild to moderately active ulcerative colitis received MMX
      mesalamine 2.4 g/day given twice daily (n = 93), 4.8 g/day given once daily (n =
      94), or placebo (n = 93) for 8 weeks. The primary end point was the percentage of
      patients in clinical and endoscopic remission (modified ulcerative colitis
      disease activity index score of < or =1, with a score of 0 for rectal bleeding
      and stool frequency, and at least a 1-point reduction in sigmoidoscopy score) at
      week 8. Patients with mucosal friability were not considered to have achieved
      this end point. RESULTS: Clinical and endoscopic remission at week 8 was achieved
      by 34.1% and 29.2% of patients receiving MMX mesalamine 2.4 g/day given twice
      daily and MMX mesalamine 4.8 g/day given once daily, respectively, versus 12.9%
      receiving placebo (P < .01). MMX mesalamine was generally well-tolerated.
      CONCLUSIONS: MMX mesalamine given once or twice daily is well-tolerated and,
      compared with placebo, demonstrated efficacy for the induction of clinical and
      endoscopic remission in mild to moderately active ulcerative colitis.

PMID- 17234559
TI  - Endoscopic papillary balloon dilation for bile duct stone: immediate and long
      term outcomes in 1000 patients.
AB  - BACKGROUND & AIMS: The long-term outcomes of endoscopic papillary balloon
      dilation (EPBD) for bile duct stone removal are not well known. METHODS: A total
      of 1000 patients with bile duct stones were treated with EPBD. After assessing
      immediate outcomes, patients were followed up for late biliary complications.
      RESULTS: Complete bile duct clearance was achieved with EPBD alone in 963
      patients (96.3%) in a mean of 1.5 endoscopic sessions. Post-EPBD pancreatitis
      developed in 48 patients (4.8%), including 1 patient graded as severe. The long
      term outcome was evaluated in 837 patients with a mean follow-up period of 4.4
      years. Biliary complications were seen in 104 patients (12.4%), and they were
      less frequent in the cholecystectomy (CCx) after EPBD group than in the
      gallbladder (GB) left in situ with stones, GB left in situ without stones, and
      CCx before EPBD groups (2.8% vs 22.6%, 9.2%, and 13.5%, respectively). Stone
      recurrence was seen in 74 patients (8.8%)--2.4%, 15.6%, 5.9%, and 10.8% in the
      CCx after EPBD, GB left in situ with stones, GB left in situ without stones, and
      CCx before EPBD groups, respectively. Lithotripsy and gallbladder status were
      identified as risk factors for stone recurrence. Cholecystitis occurred in 13
      patients (4.5%) in the GB left in situ with stones group. CONCLUSIONS: EPBD was
      effective in treating bile duct stones that were not accompanied by an
      unacceptably high risk of pancreatitis. Patients with calculous gallbladder had
      the highest risk for late complications, and cholecystectomy is recommended after
      removal of their bile duct stones.

PMID- 17234560
TI  - Compassion.

PMID- 17234561
TI  - Consciousness at work: recent research points to the power of our thoughts and
      intentions.

PMID- 17234562
TI  - Trends that will affect your future...water...water... Part one: Hot and salty.

PMID- 17234563
TI  - The art of healing and the wisdom of the unconscious: how to make the invisible
      visible.

PMID- 17234564
TI  - The homeopathic antiarthitic preparation Zeel comp. N: a review of molecular and
      clinical data.
AB  - Zeel comp. N (Zeel) is a homeopathic medication that has been widely used for
      many years for the treatment of arthritic disorders in a large number of
      countries worldwide. In recent years, a growing body of clinical and molecular
      evidence has been accumulating that shed light on the possible antiarthritic
      effects of this preparation. A number of studies report anti-inflammatory effects
      from Zeel. In vitro studies have indicated Zeel-mediated inhibition of the
      pathways involving the enzymes cyclooxygenase-1 and -2, and also the 5
      lipoxygenase pathways, affecting levels of both eicosanoids and leukotrienes.
      Thus, Zeel may reduce the main two classes of molecules responsible for arthritic
      pain and inflammation. This review describes recent research on Zeel and
      discusses the need for further studies to clarify the role of the compound in the
      antiarthritic armamentarium of complementary medicine.

PMID- 17234565
TI  - Anomalous information reception by research mediums demonstrated using a novel
      triple-blind protocol.
AB  - CONTEXT: Investigating the information reported by mediums is ultimately
      important in determining the relationship between brain and consciousness in
      addition to being of deep concern to the public. OBJECTIVE: This triple-blind
      study was designed to examine the anomalous reception of information about
      deceased individuals by research mediums under experimental conditions that
      eliminate conventional explanations. PARTICIPANTS: Eight University of Arizona
      students served as sitters: four had experienced the death of a parent; four, a
      peer. Eight mediums who had previously demonstrated an ability to report accurate
      information in a laboratory setting performed the readings. METHODOLOGY: To
      optimize potential identifiable differences between readings, each deceased
      parent was paired with a same-gender deceased peer. Sitters were not present at
      the readings; an experimenter blind to information about the sitters and deceased
      served as a proxy sitter. The mediums, blind to the sitters' and deceased's
      identities, each read two absent sitters and their paired deceased; each pair of
      sitters was read by two mediums. Each blinded sitter then scored a pair of
      itemized transcripts (one was the reading intended for him/her; the other, the
      paired control reading) and chose the reading more applicable to him/her.
      RESULTS: The findings included significantly higher ratings for intended versus
      control readings (p = 0.007, effect size = 0.5) and significant reading-choice
      results (p = 0.01). CONCLUSIONS: The results suggest that certain mediums can
      anomalously receive accurate information about deceased individuals. The study
      design effectively eliminates conventional mechanisms as well as telepathy as
      explanations for the information reception, but the results cannot distinguish
      among alternative paranormal hypotheses, such as survival of consciousness (the
      continued existence, separate from the body, of an individual's consciousness or
      personality after physical death) and super-psi (or super-ESP; retrieval of
      information via a psychic channel or quantum field).

PMID- 17234566
TI  - The impact of acupuncture and craniosacral therapy interventions on clinical
      outcomes in adults with asthma.
AB  - OBJECTIVE: Synergy has been proposed between modalities operating at different
      levels of action. Acupuncture and craniosacral therapy are two very different
      modalities for which synergy has been proposed. This study sought to test for
      such synergy and to determine if complementary therapies would improve pulmonary
      function and quality of life for people suffering from asthma, as well as
      reducing anxiety, depression, and medication usage. DESIGN: Subjects were
      randomly assignment to one of five groups: acupuncture, craniosacral therapy,
      acupuncture and craniosacral, attention control, and waiting list control.
      METHODS: Subjects received 12 sessions of equal length with pretreatment and
      posttreatment assessment of pulmonary function, asthma quality of life,
      depression, and anxiety. Medication use was also assessed. RESULTS: Synergy was
      not demonstrated. When treatment was compared with the control group,
      statistically treatment was significantly better than the control group in
      improving asthma quality of life, whereas reducing medication use with pulmonary
      function test results remained the same. However, the combination of acupuncture
      and craniosacral treatment was not superior to each therapy alone. In fact,
      although all active patients received 12 treatment sessions, those who received
      all treatments from one practitioner had statistically significant reductions in
      anxiety when compared with those receiving the same number of treatments from
      multiple practitioners. No effects on depression were found. CONCLUSIONS:
      Acupuncture and/or craniosacral therapy are potentially useful adjuncts to the
      conventional care of adults with asthma, but the combination of the two does not
      provide additional benefit over each therapy alone.

PMID- 17234567
TI  - The yin and yang of integrative clinical care, education, and research.
AB  - Communication between mainstream clinician scientists and complementary
      therapists is often problematic, in part because of different perspectives,
      assumptions, and values. However, a simple conceptual model can help conventional
      scientists and less conventional practitioners find common ground and appreciate
      their unique approaches toward achieving the same goals. The model described in
      this article has grown out of my experience in integrating complementary
      therapies and approaches into clinical care, education, and research. It uses the
      familiar yin-yang symbol from Chinese medicine to build bridges between
      mainstream Western clinician-scientists and complementary therapists from other
      traditions. Over the past seven years, I have developed and used this model in
      caring for patients, teaching medical students and residents, and conducting
      research in conjunction with complementary clinicians. This paper describes the
      yin-yang model as a way to integrate and enhance the understanding of different
      cultures of healthcare.

PMID- 17234568
TI  - Effects of yoga on quality of life and flexibility in menopausal women: a case
      series.

PMID- 17234569
TI  - A conspiracy of miracles qi, spirit-mind-body, and the transformation of
      healthcare. Interview by Bonnie J. Horrigan.

PMID- 17234570
TI  - The merits and pitfalls of vegetarianism.

PMID- 17234571
TI  - "Mash" today: medicine, war, and writing.

PMID- 17234572
TI  - We can't go on dying this way.

PMID- 17234573
TI  - Local action and global networking: the Nightingale Initiative for Global Health.

PMID- 17234574
TI  - Innovations in integrative healthcare education: Spaulding Rehabilitation
      Hospital--the integrative medicine project.

PMID- 17234576
TI  - Retraction notice: Padhani A. PET imaging of tumour hypoxia, Cancer Imaging 2006;
      6: s117-s121.
AB  - This article has been retracted from Cancer Imaging. The correct citation is
      Padhani AR, Krohn KA, Lewis JS, Alber M. Imaging oxygenation of human tumours.

PMID- 17234575
TI  - Ask the experts. How to counsel patients about preventing exposure of their
      children to potentially toxic house-hold products.

PMID- 17234577
TI  - Transcriptomal comparison of human dermal lymphatic endothelial cells ex vivo and
      in vitro.
AB  - The in vivo functions of lymphatic endothelial cells depend on their
      microenvironment, which cannot be fully reproduced in vitro. Because of technical
      limitations, gene expression in uncultured, "ex vivo" lymphatic endothelial cells
      has not been characterized at the molecular level. We combined tissue
      micropreparation and direct cell isolation with DNA chip experiments to identify
      159 genes differentiating human lymphatic endothelial cells from blood vascular
      endothelial cells ex vivo. The same analysis performed with cultured primary
      cells revealed that only 19 genes characteristic for lymphatic endothelium ex
      vivo retained this property upon culture, while 27 marker genes were newly
      induced. In addition, a set of panendothelial genes could be recognized. The
      propagation of lymphatic endothelial cells in culture stimulated transcription of
      genes associated with cell turnover, basic metabolism, and the cytoskeleton. On
      the other hand, there was downregulation of genes encoding extracellular matrix
      components, signaling via transmembrane tyrosine kinase pathways and the
      chemokine (C-C) ligand 21. Direct ex vivo analysis of the lymphatic endothelial
      cell transcriptome is helpful for the understanding of the physiology of the
      lymphatic vascular system and of the pathogenesis of its diseases.

PMID- 17234578
TI  - The cationic amino acid transporters CAT1 and CAT3 mediate NMDA receptor
      activation-dependent changes in elaboration of neuronal processes via the
      mammalian target of rapamycin mTOR pathway.
AB  - Neuronal activity influences protein synthesis and neuronal growth. Availability
      of nutrients, especially leucine and arginine, regulates the mammalian target of
      rapamycin (mTOR) pathway that controls cell growth. We show that NMDA receptor
      activation markedly reduces arginine transport by decreasing surface expression
      of the cationic amino acid transporters (CAT) 1 and 3. Depletion of CAT1 and CAT3
      by RNA interference blocks influences of NMDA receptor activation on the mTOR
      pathway and neuronal process formation. Thus, the CATs mediate influences of NMDA
      receptor activation on the mTOR pathway that regulates neuronal processes.

PMID- 17234579
TI  - Fibroblast growth factor (FGF)-2 and FGF receptor 3 are required for the
      development of the substantia nigra, and FGF-2 plays a crucial role for the
      rescue of dopaminergic neurons after 6-hydroxydopamine lesion.
AB  - Basic fibroblast growth factor (FGF-2) is involved in the development and
      maintenance of the nervous system. Exogenous administration of FGF-2 increased
      dopaminergic (DA) graft survival in different animal models of Parkinson's
      disease. To study the physiological function of the endogenous FGF-2 system, we
      analyzed the nigrostriatal system of mice lacking FGF-2, mice overexpressing FGF
      2, and FGF-receptor-3 (FGFR3)-deficient mice both after development and after 6
      hydroxydopamine lesion. FGFR3-deficient mice (+/-) displayed a reduced number of
      DA neurons compared with the respective wild type. Whereas absence of FGF-2 led
      to significantly increased numbers of DA neurons, enhanced amount of the growth
      factor in mice overexpressing FGF-2 resulted in less tyrosine hydroxylase
      expression and a reduced DA cell density. The volumes of the substantia nigra
      were enlarged in both FGF-2(-/-) and in FGF-2 transgenic mice, suggesting an
      important role of FGF-2 for the establishment of the proper number of DA neurons
      and a normal sized substantia nigra during development. In a second set of
      experiments, the putative relevance of endogenous FGF-2 after neurotoxin
      application was investigated regarding the number of rescued DA neurons after
      partial 6-OHDA lesion. Interestingly, the results after lesion were directly
      opposed to the results after development: significantly less DA neurons survived
      in FGF-2(-/-) mice compared with wild-type mice. Together, the results indicate
      that FGFR3 is crucially involved in regulating the number of DA neurons. The lack
      of FGF-2 seems to be (over)compensated during development, but, after lesion,
      compensation mechanisms fail. The transgenic mice showed that endogenous FGF-2
      protects DA neurons from 6-OHDA neurotoxicity.

PMID- 17234580
TI  - Goal-related activity in hippocampal place cells.
AB  - Place cells are hippocampal neurons whose discharge is strongly related to a
      rat's location in its environment. The existence of place cells has led to the
      proposal that they are part of an integrated neural system dedicated to spatial
      navigation, an idea supported by the discovery of strong relationships between
      place cell activity and spatial problem solving. To further understand such
      relationships, we examined the discharge of place cells recorded while rats
      solved a place navigation task. We report that, in addition to having widely
      distributed firing fields, place cells also discharge selectively while the
      hungry rat waits in an unmarked goal location to release a food pellet. Such
      firing is not duplicated in other locations outside the main firing field even
      when the rat's behavior is constrained to be extremely similar to the behavior at
      the goal. We therefore propose that place cells provide both a geometric
      representation of the current environment and a reflection of the rat's
      expectancy that it is located correctly at the goal. This on-line feedback about
      a critical aspect of navigational performance is proposed to be signaled by the
      synchronous activity of the large fraction of place cells active at the goal. In
      combination with other (prefrontal) cells that provide coarse encoding of goal
      location, hippocampal place cells may therefore participate in a neural network
      allowing the rat to plan accurate trajectories in space.

PMID- 17234581
TI  - Nanodomains of single Ca2+ channels contribute to action potential repolarization
      in cortical neurons.
AB  - The precise shape of action potentials in cortical neurons is a key determinant
      of action potential-dependent Ca2+ influx, as well as of neuronal signaling, on a
      millisecond scale. In cortical neurons, Ca2+-sensitive K+ channels, or BK
      channels (BKChs), are crucial for action potential termination, but the precise
      functional interplay between Ca2+ channels and BKChs has remained unclear. In
      this study, we investigate the mechanisms allowing for rapid and reliable
      activation of BKChs by single action potentials in hippocampal granule cells and
      the impact of endogenous Ca2+ buffers. We find that BKChs are operated by
      nanodomains of single Ca2+ channels. Using a novel approach based on a linear
      approximation of buffered Ca2+ diffusion in microdomains, we quantitatively
      analyze the prolongation of action potentials by the Ca2+ chelator BAPTA. This
      analysis allowed us to estimate that the mean diffusional distance for Ca2+ ions
      from a Ca2+ channel to a BKCh is approximately 13 nm. This surprisingly short
      diffusional distance cannot be explained by a random distribution of Ca2+
      channels and renders the activation of BKChs insensitive to the relatively high
      concentrations of endogenous Ca2+ buffers in hippocampal neurons. These data
      suggest that tight colocalization of the two types of channels permits
      hippocampal neurons to regulate global Ca2+ signals by a high cytoplasmic Ca2+
      buffer capacity without affecting the fast and brief activation of BKChs required
      for proper repolarization of action potentials.

PMID- 17234582
TI  - Tonic enhancement of endocannabinoid-mediated retrograde suppression of
      inhibition by cholinergic interneuron activity in the striatum.
AB  - Tonically active cholinergic interneurons in the striatum modulate activities of
      striatal outputs from medium spiny (MS) neurons and significantly influence
      overall functions of the basal ganglia. Cellular mechanisms of this modulation
      are not fully understood. Here we show that ambient acetylcholine (ACh) derived
      from tonically active cholinergic interneurons constitutively upregulates
      depolarization-induced release of endocannabinoids from MS neurons. The released
      endocannabinoids cause transient suppression of inhibitory synaptic inputs to MS
      neurons through acting retrogradely onto presynaptic CB1 cannabinoid receptors.
      The effects were mediated by postsynaptic M(1) subtype of muscarinic ACh
      receptors, because the action of a muscarinic agonist to release endocannabinoids
      and the enhancement of depolarization-induced endocannabinoid release by ambient
      ACh were both deficient in M1 knock-out mice and were blocked by postsynaptic
      infusion of guanosine-5'-O-(2-thiodiphosphate). Suppression of spontaneous
      firings of cholinergic interneurons by inhibiting Ih current reduced the
      depolarization-induced release of endocannabinoids. Conversely, elevation of
      ambient ACh concentration by inhibiting choline esterase significantly enhanced
      the endocannabinoid release. Paired recording from a cholinergic interneuron and
      an MS neuron revealed that the activity of single cholinergic neuron could
      influence endocannabinoid-mediated signaling in neighboring MS neurons. These
      results clearly indicate that striatal endocannabinoid-mediated modulation is
      under the control of cholinergic interneuron activity. By immunofluorescent and
      immunoelectron microscopic examinations, we demonstrated that M1 receptor was
      densely distributed in perikarya and dendrites of dopamine D1 or D2 receptor
      positive MS neurons. Thus, we have disclosed a novel mechanism by which the
      muscarinic system regulates striatal output and may contribute to motor control.

PMID- 17234584
TI  - Metastability of active CA3 networks.
AB  - The brain is spontaneously active even in the absence of external input. This
      ongoing background activity impacts neural information processing. We used
      functional multineuron calcium imaging (fMCI) to analyze the net structure of
      spontaneous CA3 network activity in hippocampal slice cultures loaded with Oregon
      Green 488 BAPTA-1 using a spinning disk confocal microscope (10-30 frames/s).
      Principal component analysis revealed that network states, defined by active cell
      ensembles, were stable but heterogenous and discrete. These states were
      stabilized through synaptic activity and maintained against external
      perturbations. A few discrete states emerged during our observation period of up
      to 30 min. Networks tended to stay in a single state for tens of seconds and then
      suddenly jump to a new state. After a state transition, the old state was rarely,
      if ever, revisited by the network during our observation period. This temporal
      profile of state transitions could not be simulated by a hidden Markov model,
      indicating that the state dynamics is nonrandomly organized. Within each state,
      the pattern of network activity tended to stabilize in a specific configuration.
      Neither maintenance nor transition of the network states required NMDA receptor
      activity. These findings suggest that the network states are metastable, rather
      than multistable, and might be governed by local attractor-like dynamics. The
      fMCI data analyzed here are available at http://hippocampus.jp/data/

PMID- 17234583
TI  - Neurofilaments switch between distinct mobile and stationary states during their
      transport along axons.
AB  - We have developed a novel pulse-escape fluorescence photoactivation technique to
      investigate the long-term pausing behavior of axonal neurofilaments. Cultured
      sympathetic neurons expressing a photoactivatable green fluorescent neurofilament
      fusion protein were illuminated with violet light in a short segment of axon to
      create a pulse of fluorescent neurofilaments. Neurofilaments departed from the
      photoactivated regions at rapid velocities, but the overall loss of fluorescence
      was slow because many of the neurofilaments paused for long periods of time
      before moving. The frequency of neurofilament departure was more rapid initially
      and slower at later times, resulting in biphasic decay kinetics. By computational
      simulation of the kinetics, we show that the neurofilaments switched between two
      distinct states: a mobile state characterized by intermittent movements and short
      pauses (average = 30 s) and a stationary state characterized by remarkably long
      pauses (average = 60 min). On average, the neurofilaments spent 92% of their time
      in the stationary state. Combining short and long pauses, they paused for 97% of
      the time, resulting in an average transport rate of 0.5 mm/d. We speculate that
      the relative proportion of the time that neurofilaments spend in the stationary
      state may be a principal determinant of their transport rate and distribution
      along axons, and a potential target of mechanisms that lead to abnormal
      neurofilament accumulations in disease.

PMID- 17234585
TI  - Deficits in short-latency tracking eye movements after chemical lesions in monkey
      cortical areas MT and MST.
AB  - Past work has suggested that the medial superior temporal area (MST) is involved
      in the initiation of three kinds of eye movements at short latency by large-field
      visual stimuli. These eye movements consist of (1) version elicited by linear
      motion (the ocular following response), (2) vergence elicited by binocular
      parallax (the disparity vergence response), and (3) vergence elicited by global
      motion toward or away from the fovea (the radial-flow vergence response). We
      investigated this hypothesis by recording the effects of ibotenic acid injections
      in the superior temporal sulcus (STS) of both hemispheres in five monkeys. After
      the injections, all three kinds of eye movements were significantly impaired,
      with the magnitude of the impairments often showing a strong correlation with the
      extent of the morphological damage in the three subregions of the STS: dorsal MST
      on the anterior bank, lateral MST and middle temporal area on the posterior bank.
      However, the extent of the lesions in the three subregions often covaried,
      rendering it difficult to assess their relative contributions to the various
      deficits. The effects of the lesions on other aspects of oculomotor behavior that
      are known to be important for the normal functioning of the three tracking
      mechanisms (e.g., ocular stability, fixation disparity) were judged to be
      generally minor and to contribute little to the impairments. We conclude that,
      insofar as MST sustained significant damage in all injected hemispheres, our
      findings are consistent with the hypothesis that MST is a primary site for
      initiating all three visual tracking eye movements at ultra-short latencies.

PMID- 17234586
TI  - Differential roles of NR2A- and NR2B-containing NMDA receptors in activity
      dependent brain-derived neurotrophic factor gene regulation and limbic
      epileptogenesis.
AB  - Fleeting activation of NMDA receptors (NMDARs) induces long-term modification of
      synaptic connections and refinement of neuronal circuits, which may underlie
      learning and memory and contribute to pathogenesis of a diversity of neurological
      diseases, including epilepsy. Here, we found that NR2A and NR2B subunit
      containing NMDARs were coupled to distinct intracellular signaling, resulting in
      differential BDNF expression and extracellular signal-regulated kinase 1/2
      (ERK1/2) activation. Selective activation of NR2A-containing NMDARs increased
      BDNF gene expression. Activation of NR2B-containing NMDARs led to ERK1/2
      phosphorylation. Furthermore, selectively blocking NR2A-containing NMDARs
      impaired epileptogenesis and the development of mossy fiber sprouting in the
      kindling and pilocarpine rat models of limbic epilepsy, whereas inhibiting NR2B
      containing NMDARs had no effects in epileptogenesis and mossy fiber sprouting.
      Interestingly, blocking either NR2A- or NR2B-containing NMDARs decreased status
      epilepticus-induced neuronal cell death. The specific requirement of NR2A and its
      downstream signaling for epileptogenesis implicates attractive new targets for
      the development of drugs that prevent epilepsy in patients with brain injury.

PMID- 17234587
TI  - Networks of parvalbumin-positive interneurons in the basolateral amygdala.
AB  - The amygdala is a temporal lobe structure that is required for processing
      emotional information. Polymodal sensory information enters the amygdala at the
      level of the basolateral amygdala (BLA) and undergoes local processing, after
      which the behavioral and autonomic responses that accompany emotions are
      initiated. Two main neuron types are present in the BLA, pyramidal-like principal
      neurons that use glutamate as their transmitter, and local circuit interneurons
      that use GABA as their transmitter. Although the properties of principal neurons
      are known in some detail, very little is known about the properties of BLA
      interneurons or the local circuits in which they are involved. Using mice in
      which EGFP (enhanced green fluorescent protein) is expressed under the control of
      the parvalbumin promoter, we characterized the properties of parvalbumin-positive
      interneurons in the BLA. By making recordings from interneuron-interneuron and
      interneuron-principal neuron pairs, we analyzed the intrinsic circuitry of the
      BLA. We show that parvalbumin-positive interneurons can be divided into four
      subtypes as defined by their firing properties. Interneurons are electrically
      coupled in subtype-specific networks and exhibit subtype-specific heterogeneities
      in their synaptic dynamics and patterns of connectivity. We propose that these
      properties allow networks of parvalbumin-expressing neurons to perform an array
      of information-processing tasks within the BLA.

PMID- 17234588
TI  - A single amino acid substitution (Cys249Trp) in Crb1 causes retinal degeneration
      and deregulates expression of pituitary tumor transforming gene Pttg1.
AB  - Different mutations in the human Crumbs homolog-1 (CRB1) gene cause a variety of
      retinal dystrophies, such as Leber congenital amaurosis, early onset retinitis
      pigmentosa (e.g., RP12), RP with Coats-like exudative vasculopathy, and pigmented
      paravenous retinochoroidal atrophy. Loss of Crb1 leads to displaced
      photoreceptors and focal degeneration of all neural layers attributable to loss
      of adhesion between photoreceptors and Muller glia cells. To gain insight into
      genotype-phenotype relationship, we generated Crb1(C249W) mice that harbor an
      amino acid substitution (Cys249Trp) in the extracellular sixth calcium-binding
      epidermal growth factor domain of Crb1. Our analysis showed that Crb1(C249W) as
      wild-type protein trafficked to the subapical region adjacent to adherens
      junctions at the outer limiting membrane (OLM). Hence, these data suggest correct
      trafficking of the corresponding mutant CRB1 in RP12 patients. Crb1(C249W) mice
      showed loss of photoreceptors in the retina, relatively late compared with mice
      lacking Crb1. Scanning laser ophthalmoscopy revealed autofluorescent dots that
      presumably represent layer abnormalities after OLM disturbance. Gene expression
      analyses revealed lower levels of pituitary tumor transforming gene 1 (Pttg1)
      transcripts in Crb1(C249W/-) knock-in and Crb1(-/-) knock-out compared with
      control retinas. Exposure to white light decreased levels of Pttg1 in Crb1 mutant
      retinas. We hypothesize deregulation of Pttg1 expression attributable to a C249W
      substitution in the extracellular domain of Crb1.

PMID- 17234589
TI  - Activation of PAR-1 kinase and stimulation of tau phosphorylation by diverse
      signals require the tumor suppressor protein LKB1.
AB  - Aberrant phosphorylation of tau is associated with a number of neurodegenerative
      diseases, including Alzheimer's disease (AD). The molecular mechanisms by which
      tau phosphorylation is regulated under normal and disease conditions are not well
      understood. Microtubule affinity regulating kinase (MARK) and PAR-1 have been
      identified as physiological tau kinases, and aberrant phosphorylation of MARK/PAR
      1 target sites in tau has been observed in AD patients and animal models. Here we
      show that phosphorylation of PAR-1 by the tumor suppressor protein LKB1 is
      required for PAR-1 activation, which in turn promotes tau phosphorylation in
      Drosophila. Diverse stress stimuli, such as high osmolarity and overexpression of
      the human beta-amyloid precursor protein, can promote PAR-1 activation and tau
      phosphorylation in an LKB1-dependent manner. These results reveal a new function
      for the tumor suppressor protein LKB1 in a signaling cascade through which the
      phosphorylation and function of tau is regulated by diverse signals under
      physiological and pathological conditions.

PMID- 17234590
TI  - Cortical discrimination of complex natural stimuli: can single neurons match
      behavior?
AB  - A central finding in many cortical areas is that single neurons can match
      behavioral performance in the discrimination of sensory stimuli. However, whether
      this is true for natural behaviors involving complex natural stimuli remains
      unknown. Here we use the model system of songbirds to address this problem.
      Specifically, we investigate whether neurons in field L, the homolog of primary
      auditory cortex, can match behavioral performance in the discrimination of
      conspecific songs. We use a classification framework based on the (dis)similarity
      between single spike trains to quantify neural discrimination. We use this
      framework to investigate the discriminability of single spike trains in field L
      in response to conspecific songs, testing different candidate neural codes
      underlying discrimination. We find that performance based on spike timing is
      significantly higher than performance based on spike rate and interspike
      intervals. We then assess the impact of temporal correlations in spike trains on
      discrimination. In contrast to widely discussed effects of correlations in
      limiting the accuracy of a population code, temporal correlations appear to
      improve the performance of single neurons in the majority of cases. Finally, we
      compare neural performance with behavioral performance. We find a diverse range
      of performance levels in field L, with neural performance matching behavioral
      accuracy only for the best neurons using a spike-timing-based code.

PMID- 17234591
TI  - Ankyrin-dependent and -independent mechanisms orchestrate axonal
      compartmentalization of L1 family members neurofascin and L1/neuron-glia cell
      adhesion molecule.
AB  - Axonal initial segments (IS) and nodes of Ranvier are functionally important
      membrane subdomains in which the clustering of electrogenic channels enables
      action potential initiation and propagation. In addition, the initial segment
      contributes to neuronal polarity by serving as a diffusion barrier. To study the
      mechanisms of axonal compartmentalization, we focused on two L1 family of cell
      adhesion molecules (L1-CAMs) [L1/neuron-glia cell adhesion molecule (L1/NgCAM)
      and neurofascin (NF)] and two neuronal ankyrins (ankB and ankG). NF and ankG
      accumulate specifically at the initial segment, whereas L1/NgCAM and ankB are
      expressed along the entire lengths of axons. We find that L1/NgCAM and NF show
      distinct modes of steady-state accumulation during axon outgrowth in cultured
      hippocampal neurons. Despite their different steady-state localizations, both
      L1/NgCAM and NF show slow diffusion and low detergent extractability specifically
      in the initial segment but fast diffusion and high detergent extractability in
      the distal axon. We propose that L1-CAMs do not strongly bind ankB in the distal
      axon because of spatial regulation of ankyrin affinity by phosphorylation. NF,
      conversely, is initially enriched in an ankyrin-independent manner in the axon
      generally and accumulates progressively in the initial segment attributable to
      preferential binding to ankG. Our results suggest that NF and L1/NgCAM accumulate
      in the axon by an ankyrin-independent pathway, but retention at the IS requires
      ankyrin binding.

PMID- 17234592
TI  - In vivo identification and manipulation of the Ca2+ selectivity filter in the
      Drosophila transient receptor potential channel.
AB  - Null mutations in the transient receptor potential (trp) gene eliminate the
      major, Ca2+-selective component of the light-sensitive conductance in Drosophila
      photoreceptors. Although it is the prototypical member of the TRP ion channel
      superfamily, conclusive evidence that TRP is a pore-forming channel subunit in
      vivo is lacking. We show here that mutating a specific acidic residue (Asp621) in
      the putative pore virtually eliminated Ca2+ permeation in vivo and altered other
      biophysical properties of the native TRP conductance. The results identify Asp621
      as a critical residue of the TRP Ca2+ selectivity filter, provide the first
      rigorous demonstration that a TRP protein is a pore-forming subunit in any native
      system, and point to the likely location of the pore in mammalian canonical TRP
      channels. The specific elimination of Ca2+ permeation in TRP also provided a
      unique opportunity to address the roles of Ca2+ influx in vivo. We found that
      Asp621 mutations profoundly affected several key aspects of the light response
      and caused light-dependent retinal degeneration.

PMID- 17234593
TI  - Deficiency in Na,K-ATPase alpha isoform genes alters spatial learning, motor
      activity, and anxiety in mice.
AB  - Several disorders have been associated with mutations in Na,K-ATPase alpha
      isoforms (rapid-onset dystonia parkinsonism, familial hemiplegic migraine type
      2), as well as reduction in Na,K-ATPase content (depression and Alzheimer's
      disease), thereby raising the issue of whether haploinsufficiency or altered
      enzymatic function contribute to disease etiology. Three isoforms are expressed
      in the brain: the alpha1 isoform is found in many cell types, the alpha2 isoform
      is predominantly expressed in astrocytes, and the alpha3 isoform is exclusively
      expressed in neurons. Here we show that mice heterozygous for the alpha2 isoform
      display increased anxiety-related behavior, reduced locomotor activity, and
      impaired spatial learning in the Morris water maze. Mice heterozygous for the
      alpha3 isoform displayed spatial learning and memory deficits unrelated to
      differences in cued learning in the Morris maze, increased locomotor activity, an
      increased locomotor response to methamphetamine, and a 40% reduction in
      hippocampal NMDA receptor expression. In contrast, heterozygous alpha1 isoform
      mice showed increased locomotor response to methamphetamine and increased basal
      and stimulated corticosterone in plasma. The learning and memory deficits
      observed in the alpha2 and alpha3 heterozygous mice reveal the Na,K-ATPase to be
      an important factor in the functioning of pathways associated with spatial
      learning. The neurobehavioral changes seen in heterozygous mice suggest that
      these mouse models may be useful in future investigations of the associated human
      CNS disorders.

PMID- 17234594
TI  - Abeta40 inhibits amyloid deposition in vivo.
AB  - Numerous studies have established a pivotal role for Abeta42 in Alzheimer's
      disease (AD) pathogenesis. In contrast, although Abeta40 is the predominant form
      of amyloid beta (Abeta) produced and accumulates to a variable degree in the
      human AD brain, its role in AD pathogenesis has not been established. It has
      generally been assumed that an increase in Abeta40 would accelerate amyloid
      plaque formation in vivo. We have crossed BRI-Abeta40 mice that selectively
      express high levels of Abeta40 with both Tg2576 (APPswe, K670N+M671L) mice and
      BRI-Abeta42A mice expressing Abeta42 selectively and analyzed parenchymal and
      cerebrovascular Abeta deposition in the bitransgenic mice compared with their
      singly transgenic littermates. In the bitransgenic mice, the increased steady
      state levels of Abeta40 decreased Abeta deposition by 60-90%. These results
      demonstrate that Abeta42 and Abeta40 have opposing effects on amyloid deposition:
      Abeta42 promotes amyloid deposition but Abeta40 inhibits it. In addition,
      increasing Abeta40 levels protected BRI-Abeta40/Tg2576 mice from the premature
      death phenotype observed in Tg2576 mice. The protective properties of Abeta40
      with respect to amyloid deposition suggest that strategies that preferentially
      target Abeta40 may actually worsen the disease course and that selective
      increases in Abeta40 levels may actually reduce the risk for development of AD.

PMID- 17234595
TI  - Astrocyte and muscle-derived secreted factors differentially regulate motoneuron
      survival.
AB  - During development, motoneurons (MNs) undergo a highly stereotyped, temporally
      and spatially defined period of programmed cell death (PCD), the result of which
      is the loss of 40-50% of the original neuronal population. Those MNs that survive
      are thought to reflect the successful acquisition of limiting amounts of trophic
      factors from the target. In contrast, maturation of MNs limits the need for
      target-derived trophic factors, because axotomy of these neurons in adulthood
      results in minimal neuronal loss. It is unclear whether MNs lose their need for
      trophic factors altogether or whether, instead, they come to rely on other cell
      types for nourishment. Astrocytes are known to supply trophic factors to a
      variety of neuronal populations and thus may nourish MNs in the absence of target
      derived factors. We investigated the survival-promoting activities of muscle- and
      astrocyte-derived secreted factors and found that astrocyte-conditioned media
      (ACM) was able to save substantially more motoneurons in vitro than muscle
      conditioned media (MCM). Our results indicate that both ACM and MCM are
      significant sources of MN trophic support in vitro and in ovo, but only ACM can
      rescue MNs after unilateral limb bud removal. Furthermore, we provide evidence
      suggesting that MCM facilitates the death of a subpopulation of MNs in a p75(NTR)
      - and caspase-dependent manner; however, maturation in ACM results in MN trophic
      independence and reduced vulnerability to this negative, pro-apoptotic influence
      from the target.

PMID- 17234596
TI  - Roles of subthreshold calcium current and sodium current in spontaneous firing of
      mouse midbrain dopamine neurons.
AB  - We used a preparation of acutely dissociated neurons to quantify the ionic
      currents driving the spontaneous firing of substantia nigra pars compacta
      neurons, isolated from transgenic mice in which the tyrosine hydroxylase promoter
      drives expression of human placental alkaline phosphatase (PLAP) on the outer
      surface of the cell membrane. Dissociated neurons identified by fluorescent
      antibodies to PLAP showed firing properties similar to those of dopaminergic
      neurons in brain slice, including rhythmic spontaneous firing of broad action
      potentials and, in some cells, rhythmic oscillatory activity in the presence of
      tetrodotoxin (TTX). Spontaneous activity in TTX had broader, smaller spikes than
      normal pacemaking and was stopped by removal of external calcium. Normal
      pacemaking was also consistently silenced by replacement of external calcium by
      cobalt and was slowed by more specific calcium channel blockers. Nimodipine
      produced a slowing of pacemaking frequency. Pacemaking was also slowed by the P/Q
      channel blocker omega-Aga-IVA, but the N-type channel blocker omega-conotoxin
      GVIA had no effect. In voltage-clamp experiments, using records of pacemaking as
      command voltage, cobalt-sensitive current and TTX-sensitive current were both
      sizeable at subthreshold voltages between spikes. Cobalt-sensitive current was
      consistently larger than TTX-sensitive current at interspike voltages from -70 to
      -50 mV, with TTX-sensitive current larger at voltages positive to -45 mV. These
      results support previous evidence for a major role of voltage-dependent calcium
      channels in driving pacemaking of midbrain dopamine neurons and suggest that
      multiple calcium channel types contribute to this function. The results also show
      a significant contribution of subthreshold TTX-sensitive sodium current.

PMID- 17234597
TI  - Generation of distinct types of periglomerular olfactory bulb interneurons during
      development and in adult mice: implication for intrinsic properties of the
      subventricular zone progenitor population.
AB  - The subventricular zone (SVZ) of the lateral ventricle develops from residual
      progenitors of the embryonic lateral ganglionic eminence (LGE) and maintains
      neurogenic activity throughout life. Precursors from LGE/SVZ migrate to the
      olfactory bulb (OB) where they differentiate into local interneurons, principally
      in the granule layer and glomerular layer (GL). By in situ dye labeling, we show
      that neonatal and adult SVZ progenitors differentially contribute to
      neurochemically distinct types of periglomerular interneurons in the GL. Namely,
      calbindin-positive periglomerular cells are preferentially generated during early
      life, whereas calretinin- and tyrosine hydroxylase-expressing neurons are mainly
      produced at later ages. Furthermore, homochronic/heterochronic transplantation
      demonstrates that progenitor cells isolated from the LGE or SVZ at different
      stages (embryonic day 15 and postnatal days 2 and 30) engraft into the SVZ of
      neonatal or adult mice, migrate to the OB, and differentiate into local
      interneurons, including granule and periglomerular cells as well as other types
      of interneurons. The total number of integrated cells and the relative proportion
      of granule or periglomerular neurons change, according to the donor age, whereas
      they are weakly influenced by the recipient age. Analysis of the neurochemical
      phenotypes acquired by transplanted cells in the GL shows that donor cells of
      different ages also differentiate according to their origin, regardless of the
      host age. This suggests that progenitor cells at different ontogenetic stages are
      intrinsically directed toward specific lineages. Neurogenic processes occurring
      during development and in adult OB are not equivalent and produce different types
      of periglomerular interneurons as a consequence of intrinsic properties of the
      SVZ progenitors.

PMID- 17234598
TI  - The RNA-binding protein HuD binds acetylcholinesterase mRNA in neurons and
      regulates its expression after axotomy.
AB  - After axotomy, expression of acetylcholinesterase (AChE) is greatly reduced in
      the superior cervical ganglion (SCG); however, the molecular events involved in
      this response remain unknown. Here, we first examined AChE mRNA levels in the
      brain of transgenic mice that overexpress human HuD. Both in situ hybridization
      and reverse transcription-PCR demonstrated that AChE transcript levels were
      increased by more than twofold in the hippocampus of HuD transgenic mice.
      Additionally, direct interaction between the HuD transgene product and AChE mRNA
      was observed. Next, we examined the role of HuD in regulating AChE expression in
      intact and axotomized rat SCG neurons. After axotomy of the adult rat SCG
      neurons, AChE transcript levels decreased by 50 and 85% by the first and fourth
      day, respectively. In vitro mRNA decay assays indicated that the decrease in AChE
      mRNA levels resulted from changes in the stability of presynthesized transcripts.
      A combination of approaches performed using the region that directly encompasses
      an adenylate and uridylate (AU)-rich element within the AChE 3'-untranslated
      region demonstrated a decrease in RNA-protein complexes in response to axotomy of
      the SCG and, specifically, a decrease in HuD binding. After axotomy, HuD
      transcript and protein levels also decreased. Using a herpes simplex virus
      construct containing the human HuD sequence to infect SCG neurons in vivo, we
      found that AChE and GAP-43 mRNA levels were maintained in the SCG after axotomy.
      Together, the results of this study demonstrate that AChE expression in neurons
      of the rat SCG is regulated via post-transcriptional mechanisms that involve the
      AU-rich element and HuD.

PMID- 17234599
TI  - Long-term sensitization training produces spike narrowing in Aplysia sensory
      neurons.
AB  - Both short- and long-term sensitization of withdrawal reflexes of Aplysia are
      attributable at least in part to facilitation of the sensorimotor synapse.
      Previously, short-term synaptic facilitation has been associated with spike
      broadening and no change in temporal dynamics of burst transmission. In the
      present study, we examined whether long-term sensitization (LTS) is also
      associated with spike broadening and whether long-term synaptic facilitation is
      accompanied by changes in temporal dynamics. The results indicate that the
      temporal dynamics of the sensorimotor synapse are preserved after long-term
      facilitation. However, in contrast to short-term sensitization, LTS was
      accompanied by spike narrowing. The spike narrowing was observed both in
      centrally triggered spikes in isolated ganglia and in peripherally triggered
      spikes in reduced tail preparations. In addition, in reduced tail preparations,
      fewer spike failures in the afferent discharge of sensory neurons occurred in
      response to tail stimulation after ipsilateral LTS. Collectively, the results
      reveal that long-term sensitization affects the spike waveform of sensory neurons
      and enhances the sensory neuron responses to peripheral stimuli, but does not
      modify the synaptic dynamics of homosynaptic depression.

PMID- 17234600
TI  - Impaired stress-coping and fear extinction and abnormal corticolimbic morphology
      in serotonin transporter knock-out mice.
AB  - A lesser-expressing form of the human 5-HT transporter (5-HTT) gene has been
      associated with increased fear and anxiety and vulnerability to the effects of
      stress. These phenotypic abnormalities are linked to functional and anatomical
      disturbances in a neural pathway connecting the prefrontal cortex (PFC) and
      amygdala. Likewise, rodent and nonhuman primate studies indicate a major role for
      PFC and amygdala in the mediation of fear- and stress-related behaviors. We used
      a 5-HTT knock-out (KO) mouse to examine the effects of genetically driven loss of
      5-HTT function for the following: (1) depression-related behavior in response to
      repeated stress, and pavlovian fear conditioning, extinction, and extinction
      recall; and (2) dendritic morphology and spine density of Golgi-stained pyramidal
      neurons in the infralimbic cortex (IL) and the basolateral amygdala (BLA). 5-HTT
      KO mice exhibited increased depressive-like immobility after repeated exposure to
      forced swim stress, compared with wild-type (WT) controls. Whereas fear
      conditioning and fear extinction was normal, 5-HTT KO mice exhibited a
      significant deficit in extinction recall. The apical dendritic branches of IL
      pyramidal neurons in 5-HTT KO mice were significantly increased in length
      relative to WT mice. Pyramidal neurons in BLA had normal dendritic morphology but
      significantly greater spine density in 5-HT KO mice compared with WT mice.
      Together, the present findings demonstrate a specific phenotypic profile of fear-
      and stress-related deficits in 5-HTT KO mice, accompanied by morphological
      abnormalities in two key neural loci. These data provide insight into the
      behavioral sequelae of loss of 5-HTT gene function and identify potential neural
      substrates underlying these phenotypes.

PMID- 17234601
TI  - Functional heterogeneity of retinal dopaminergic neurons underlying their
      multiple roles in vision.
AB  - Dopaminergic neurons play key roles in the CNS, mediating basic mechanisms of
      vision, movement, motivation, and mood. The most accessible dopaminergic neurons
      of the vertebrate CNS are the dopaminergic amacrine cells of the retina. Here, we
      have characterized the intrinsic neural activity, synaptic input, and light
      responses of retinal dopaminergic neurons in situ, using targeted
      electrophysiological recordings of fluorescent neurons in TH::RFP (tyrosine
      hydroxylase gene promoter::red fluorescent protein) transgenic mice. Dopaminergic
      amacrine cells exhibit two classes of intrinsic bursting in the dark, shaped by
      inhibitory synaptic inputs, and two classes of light responses, ON-transient and
      ON-sustained, as well as light-independent activity, tuned to mediate specific
      dopaminergic functions in vision. The functional heterogeneity revealed in
      dopaminergic amacrine cells provides a cellular basis for the multiple roles of
      dopaminergic amacrine neurons in vision and is likely a general property of
      dopaminergic neurons throughout the CNS.

PMID- 17234602
TI  - Spatial reference frames of visual, vestibular, and multimodal heading signals in
      the dorsal subdivision of the medial superior temporal area.
AB  - Heading perception is a complex task that generally requires the integration of
      visual and vestibular cues. This sensory integration is complicated by the fact
      that these two modalities encode motion in distinct spatial reference frames
      (visual, eye-centered; vestibular, head-centered). Visual and vestibular heading
      signals converge in the primate dorsal subdivision of the medial superior
      temporal area (MSTd), a region thought to contribute to heading perception, but
      the reference frames of these signals remain unknown. We measured the heading
      tuning of MSTd neurons by presenting optic flow (visual condition), inertial
      motion (vestibular condition), or a congruent combination of both cues (combined
      condition). Static eye position was varied from trial to trial to determine the
      reference frame of tuning (eye-centered, head-centered, or intermediate). We
      found that tuning for optic flow was predominantly eye-centered, whereas tuning
      for inertial motion was intermediate but closer to head-centered. Reference
      frames in the two unimodal conditions were rarely matched in single neurons and
      uncorrelated across the population. Notably, reference frames in the combined
      condition varied as a function of the relative strength and spatial congruency of
      visual and vestibular tuning. This represents the first investigation of spatial
      reference frames in a naturalistic, multimodal condition in which cues may be
      integrated to improve perceptual performance. Our results compare favorably with
      the predictions of a recent neural network model that uses a recurrent
      architecture to perform optimal cue integration, suggesting that the brain could
      use a similar computational strategy to integrate sensory signals expressed in
      distinct frames of reference.

PMID- 17234603
TI  - Imaging cerebral gene transcripts in live animals.
AB  - To circumvent the limitations of using postmortem brain in molecular assays, we
      used avidin-biotin binding to couple superparamagnetic iron oxide nanoparticles
      (SPIONs) (15-20 nm) to phosphorothioate-modified oligodeoxynucleotides (sODNs)
      with sequence complementary to c-fos and beta-actin mRNA (SPION-cfos and SPION
      beta-actin, respectively) (14-22 nm). The Stern-Volmer constant for the complex
      of SPION and fluorescein isothiocyanate (FITC)-sODN is 3.1 x 10(6)/m. We studied
      the feasibility of using the conjugates for in vivo magnetic resonance imaging
      (MRI) to monitor gene transcription, and demonstrated that these complexes at 40
      mug of Fe per kilogram of body weight were retained at least 1 d after
      intracerebroventricular infusion into the left ventricle of C57Black6 mice. SPION
      retention measured by MRI as T(2)* or R(2)* maps (R(2)* = 1/T(2)*) was compared
      with histology of iron oxide (Prussian blue) and FITC-labeled sODN. We observed
      significant reduction in magnetic resonance (MR) T(2)* signal in the right cortex
      and striatum; retention of SPION-cfos and SPION-beta-actin positively correlated
      with c-fos and beta-actin mRNA maps obtained from in situ hybridization.
      Histological examination showed that intracellular iron oxide and FITC-sODN
      correlated positively with in vivo MR signal reduction. Furthermore, in animals
      that were administered SPION-cfos and amphetamine (4 mg/kg, i.p.), retention was
      significantly elevated in the nucleus accumbens, striatum, and medial prefrontal
      cortex of the forebrain. Control groups that received SPION-cfos and saline or
      that received a SPION conjugate with a random-sequence probe and amphetamine
      showed no retention. These results demonstrated that SPION-sODN conjugates can
      detect active transcriptions of specific mRNA species in living animals with MRI.

PMID- 17234604
TI  - P450 CYP2C epoxygenase and CYP4A omega-hydroxylase mediate ciprofibrate-induced
      PPARalpha-dependent peroxisomal proliferation.
AB  - Peroxisomal proliferators, such as ciprofibrate, are used extensively as
      effective hypolipidemic drugs. The effects of these compounds on lipid metabolism
      require ligand binding activation of the peroxisome proliferator-activated
      receptor (PPAR) alpha subtype of nuclear receptors and involve transcriptional
      activation of the metabolic pathways involved in lipid oxidative metabolism,
      transport, and disposition. omega-Hydroxylated-eicosatrienoic acids (HEETs),
      products of the sequential metabolism of arachidonic acid (AA) by the cytochrome
      P450 CYP2C epoxygenase and CYP4A omega-hydroxylase gene subfamilies, have been
      identified as potent and high-affinity ligands of PPARalpha in vitro and as
      PPARalpha activators in transient transfection assays. Using isolated rat
      hepatocytes in culture, we demonstrate that specific inhibition of either the
      CYP2C epoxygenase or the CYP4A omega-hydroxylase abrogates ciprofibrate-induced
      peroxisomal proliferation, whereas inhibition of other eicosanoid-synthesizing
      pathways had no effect. Conversely, overexpression of the rat liver CYP2C11
      epoxygenase leads to spontaneous peroxisomal proliferation, an effect that is
      reversed by a CYP inhibitor. Based on these results, we propose that HEETs may
      serve as endogenous PPARalpha ligands and that the P450 AA monooxygenases
      participate in ciprofibrate-induced peroxisomal proliferation and the activation
      of PPARalpha downstream targets.

PMID- 17234605
TI  - Compartmental analyses of plasma n-3 essential fatty acids among male and female
      smokers and nonsmokers.
AB  - The effects of cigarette smoking on n-3 essential FA metabolism were studied in
      male and female subjects by fitting the concentration-time curves of the d(5)
      labeled plasma fatty acids (FAs) originating from a dose of d(5)-18:3n-3 to a
      compartmental model of n-3 FA metabolism. For 3 weeks, female (smokers, n = 5;
      nonsmokers, n = 5) and male (smokers, n = 5; nonsmokers, n = 5) subjects
      subsisted on a beef-based diet. Beginning in the third week, subjects received a
      dose of d(5)-18:3n-3 ethyl ester (1 g). Plasma FAs were analyzed using gas
      chromatography (GC) and GC-mass spectrometry, and the kinetic rate parameters
      were determined from the concentration-time curves for d(5)-18:3n-3, d(5)-20:5n
      3, d(5)-22:5n-3, and d(5)-22:6n-3. Women smokers had a 2-fold greater percent of
      dose in plasma (5.8% vs. 2.9%; P < 0.01) and a higher fractional rate constant
      coefficient for formation of d(5)-22:6n-3 from d(5)-22:5n-3 (0.03 h(-1) vs. 0.01
      h(-1); P < 0.01), compared with nonsmokers. Male smokers had elevated total
      plasma n-3 FAs, more-rapid turnover of 18:3n-3 (13.3 mg/day(-1) vs. 4.3 mg/day(
      1); P < 0.001), a disappearance rate of d(5)-20:5n-3 that was both delayed and
      slower (0.001 h(-1) vs. 0.012 h(-1); P < 0.05), and a percentage of d(5)-20:5n-3
      directed into formation of d(5)-22:5n-3 (99% vs. 61%; P < 0.03) that was greater
      compared with nonsmokers. Smoking increased the bioavailability of n-3 FAs from
      plasma, accelerated the fractional synthetic rates, and heightened the percent
      formation of some long-chain n-3 PUFAs in men and women.

PMID- 17234606
TI  - Hair plate mechanoreceptors associated with body segments are not necessary for
      three-dimensional path integration in desert ants, Cataglyphis fortis.
AB  - In formicine ants, the hair fields associated with the neck and the petiole
      (alitrunk-petiole and petiole-gaster joints) have long been established to
      function in graviception. Here, we examine a possible role of these hair
      receptors in three-dimensional (3-D) path integration of the (formicine) desert
      ant, Cataglyphis fortis. Cataglyphis judge the ground distance when travelling
      over hills, allowing correct homing even in (unpredictably) uneven terrain. We
      eliminated the function of these hair sensors in graviception either by shaving
      the hairs or by immobilising the joints monitored by the hair plates. With that
      major component of their sense of graviception eliminated, one would expect the
      ants to disregard, or at least misgauge, the ascents and descents performed
      across hills during outbound journey. The ants should thus consider the (much
      longer) actual walking trajectory, instead of the base distance, when calculating
      their homing distance. Surprisingly, neither shaving nor immobilisation of the
      hair sensillae affected correct path integration, across both uneven terrain (3
      D) and level surface. If anything, the ants underestimated homing distance, which
      may reflect a general, safety-oriented navigation strategy. Animals that had
      performed the outbound journey with their gaster fixed in a horizontal position
      underestimated their homing so dramatically that this latter explanation cannot
      hold.

PMID- 17234607
TI  - Running stability is enhanced by a proximo-distal gradient in joint
      neuromechanical control.
AB  - We currently know little about how animals achieve dynamic stability when running
      over uneven and unpredictable terrain, often characteristic of their natural
      environment. Here we investigate how limb and joint mechanics of an avian biped,
      the helmeted guinea fowl Numida meleagris, respond to an unexpected drop in
      terrain during running. In particular, we address how joint mechanics are
      coordinated to achieve whole limb dynamics. Based on muscle-tendon architecture
      and previous studies of steady and incline locomotion, we hypothesize a proximo
      distal gradient in joint neuromechanical control. In this motor control strategy,
      (1) proximal muscles at the hip and knee joints are controlled primarily in a
      feedforward manner and exhibit load-insensitive mechanical performance, and (2)
      distal muscles at the ankle and tarsometatarso-phalangeal (TMP) joints are highly
      load-sensitive, due to intrinsic mechanical effects and rapid, higher gain
      proprioceptive feedback. Limb kinematics and kinetics during the unexpected
      perturbation reveal that limb retraction, controlled largely by the hip, remains
      similar to level running throughout the perturbed step, despite altered limb
      loading. Individual joints produce or absorb energy during both level and
      perturbed running steps, such that the net limb work depends on the balance of
      energy among the joints. The hip maintains the same mechanical role regardless of
      limb loading, whereas the ankle and TMP switch between spring-like or damping
      function depending on limb posture at ground contact. Initial knee angle sets
      limb posture and alters the balance of work among the joints, although the knee
      contributes little work itself. This distribution of joint function results in
      posture-dependent changes in work performance of the limb, which allow guinea
      fowl to rapidly produce or absorb energy in response to the perturbation. The
      results support the hypothesis that a proximo-distal gradient exists in limb
      neuromuscular performance and motor control. This control strategy allows limb
      cycling to remain constant, whereas limb posture, loading and energy performance
      are interdependent. We propose that this control strategy provides simple, rapid
      mechanisms for managing energy and controlling velocity when running over rough
      terrain.

PMID- 17234608
TI  - Active space of a movement-based signal: response to the Jacky dragon
      (Amphibolurus muricatus) display is sensitive to distance, but independent of
      orientation.
AB  - The efficacy of any animal signal is constrained by the range over which it
      remains above the sensory threshold of potential receivers. The spatial area in
      which reliable detection occurs defines active space; this is influenced by
      signal structure, the signalling environment and the sensory characteristics of
      receivers. Identification of the factors influencing active space has provided
      valuable insights into signal design, particularly in bioacoustics, in which
      signal distortion and degradation can be easily quantified. In the present study,
      we consider whether active space can similarly help to explain the design of a
      movement-based visual signal. The Jacky dragon (Amphibolurus muricatus) threat
      display is composed of five distinct motor patterns delivered in an obligatory
      sequence: tail-flicks, backward and forward foreleg waves, a push-up and a 'body
      rock'. In contrast to other communication systems, the introductory element is
      characterized by reduced intensity (average speed) but greater duration than
      subsequent motor patterns. Furthermore, the tail-flick sweeps a three-dimensional
      (3D) space around the lizard, whereas the motor patterns that follow are largely
      restricted to a single plane. Structural properties thus suggest that the active
      space of the tail-flick might be greater than that of the other motor patterns in
      the display, which would provide a parsimonious explanation for its use as an
      alerting component. We tested this prediction in a playback experiment
      incorporating 3D animations of lizard displays, comparing response probabilities
      to the factorial combination of three motor patterns, three viewing angles and
      three distances. Results suggest that the tail-flick does not have a greater
      active space than other display motor patterns, but that each degrades
      predictably with distance, thereby providing potential ranging cues. In addition,
      display components are remarkably robust to variation in receiver orientation, so
      that efficacy should be maximized in most potential signalling situations. These
      findings are consistent with the hypothesis that duration is the principal
      determinant of signal efficacy in this system.

PMID- 17234609
TI  - Serotonin stimulates [Ca2+]i elevation in ciliary ectodermal cells of
      echinoplutei through a serotonin receptor cell network in the blastocoel.
AB  - A full-length serotonin receptor mRNA from the 5Hthpr gene was sequenced from
      larvae of the sea urchin, Hemicentrotus pulcherrimus. The DNA sequence was most
      similar to 5HT-1A of the sea urchin Strongylocentrotus purpuratus found by The
      Sea Urchin Genome Project, and the protein sequence predicted the presence of
      seven transmembrane domains. Immunohistochemistry with anti-5HThpr antibodies
      indicated that the protein was expressed on blastocoelar cells that comprised the
      major blastocoelar network (serotonin receptor cell network). These network cells
      inserted their processes into the ectoderm in various regions, including the
      ciliary band region. Serotonin injected into the blastocoel stimulated a
      transient elevation of cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) in the
      ectoderm, as detected by Oregon-Green dextran, injected earlier in development.
      The calcium transient propagated as a wave at about 175 microm s(-1), but was not
      detectable in the serotonin receptor-positive cell network. In larvae treated
      with p-chlorophenylalanine, a potent and irreversible serotonin synthesis
      inhibitor, serotonin application did not stimulate [Ca(2+)](i), the serotonin
      receptor cell network did not develop properly, and the swimming behavior of the
      larvae was abnormal. However, formation of a different nervous system comprising
      synaptotagmin-possessed neurites was not affected by p-chlorophenylalanine
      treatment. These results imply that serotonin secreted from the apical ganglion
      into the blastocoel stimulates the elevation of [Ca(2+)](i) in the larval
      ectodermal cells through the serotonin receptor cell network.

PMID- 17234610
TI  - Relationship between n-3 PUFA content and energy metabolism in the flight muscles
      of a migrating shorebird: evidence for natural doping.
AB  - During their fall migration from the Arctic to South America, semipalmated
      sandpipers Calidris pusilla stop in the Bay of Fundy (east coast of Canada)
      before flying non-stop for approximately 4500 km across the ocean. Refueling
      birds double their body mass by feeding on Corophium volutator, an amphipod
      containing high amounts of n-3 polyunsaturated fatty acids (n-3 PUFA),
      particularly eicosapentaenoic (20:5) and docosahexaenoic acid (22:6). In mammals,
      high dietary intake of n-3 PUFA is known to increase capacity for oxidative
      metabolism. Therefore, we hypothesized that tissue incorporation of n-3 PUFA
      would be associated with increases in the activity of key muscle enzymes to
      upregulate energy metabolism for prolonged exercise. Birds were collected at
      various stages of fat loading to monitor changes in lipid composition and flight
      muscle enzymes simultaneously. Enzymes were measured to assess oxidative capacity
      [citrate synthase (CS)], beta-oxidation [carnitine palmitoyl transferase (CPT)
      and 3-hydroxyacyl dehydrogenase (HOAD)] and glycolytic capacity [lactate
      dehydrogenase (LDH)]. Changes in the fatty acid composition of muscle membranes
      (phospholipids) and fuel reserves (neutral lipids) were measured separately to
      distinguish between membrane-related and systemic effects of n-3 PUFA. Results
      show that muscle CS and HOAD are stimulated during refueling and that their
      activities are correlated with n-3 PUFA content in phospholipids (22:6 for CS,
      20:5 for HOAD) and in neutral lipids (20:5 for CS). This suggests that 20:5 and
      22:6 have different effects on energy metabolism and that they act via changes in
      membrane structure and systemic mechanisms. CPT and LDH did not change during
      refueling, but LDH activity was significantly related to the n-3 PUFA content of
      fuel reserves. This study shows that oxidative capacity increases rapidly during
      refueling and supports the idea that dietary n-3 PUFA are used as molecular
      signals to prime flight muscles of some long-distance migrants for extreme
      exercise.

PMID- 17234611
TI  - Effects of extracellular changes on spontaneous heart rate of normoxia- and
      anoxia-acclimated turtles (Trachemys scripta).
AB  - Heart rate (f(H)) of the anoxia-tolerant freshwater turtle (Trachemys scripta)
      during prolonged anoxia exposure is 2.5- to 5-times lower than the normoxic rate,
      but whether alterations in blood composition that accompany prolonged anoxia
      contribute to this bradycardia is unknown. We examined how temperature
      acclimation, oxygen deprivation, acidosis, hyperkalemia, hypercalcemia and
      adrenaline affect chronotropy in the turtle myocardium. We monitored spontaneous
      contraction rates of right-atrial preparations obtained from 21 degrees C- and 5
      degrees C-acclimated turtles that had been exposed to either normoxia or anoxia
      (6 h at 21 degrees C; 2 weeks at 5 degrees C). Sequential exposures to saline
      solutions were designed to mimic, in a step-wise manner, the shift from a
      normoxic to anoxic extracellular condition (for normoxia-acclimated preparations)
      or the reverse (for anoxia-acclimated preparations). Our results clearly show
      that prolonged anoxia exposure re-sets the intrinsic f(H) of turtles at both
      temperatures, with reductions in intrinsic f(H) in the range of 25%-53% compared
      with normoxia. This intrinsic change would contribute to the bradycardia observed
      with prolonged anoxia. Further, we found negative chronotropic effects of
      extracellular anoxia, acidosis and hyperkalemia, and positive chronotropic
      effects of hypercalcemia and adrenaline. The exact nature of these extracellular
      effects depended, however, on the acclimation temperature and the prior exposure
      of the animal to anoxia. With normoxia-acclimated preparations at 21 degrees C,
      combined anoxia and acidosis (pH reduced from approximately 7.8 to approximately
      7.2) significantly reduced spontaneous f(H) by 22% and subsequent exposure to
      hyperkalemia (3.5 mmol l(-1)K(+)) further decreased f(H). These negative
      chronotropic effects were ameliorated by increasing the adrenaline concentration
      from the tonic level of 1 nmol l(-1) to 60 nmol l(-1). However, in anoxia
      acclimated preparations at 21 degrees C, anoxia alone inhibited f(H) (by
      approximately 30%). This negative chronotropic effect was counteracted by both
      hypercalcemia (6 mmol l(-1) Ca(2+)) and adrenaline (60 nmol l(-1)). At 5 degrees
      C, only the combination of anoxia, acidosis (pH reduced from approximately 8.0 to
      approximately 7.5) and hyperkalemia (3.5 mmol l(-1) K(+)) significantly reduced
      spontaneous f(H) (by 23%) with preparations from normoxia-acclimated turtles.
      This negative chronotropic effect was fully reversed by hypercalcemia (10 mmol l(
      1) Ca(2+)). By contrast, spontaneous f(H) of anoxia-acclimated preparations at 5
      degrees C was not affected by any of the extracellular changes. We conclude that
      prior temperature and anoxia experiences are central to determining f(H) during
      prolonged anoxia in Trachemys scripta both as a result of the re-setting of
      pacemaker rhythm and through the potential influence of extracellular changes.

PMID- 17234612
TI  - Dimorphic sperm and the unlikely route to fertilisation in the yellow seahorse.
AB  - Uniquely among vertebrates, seahorses and pipefishes (Family Syngnathidae)
      incubate their eggs within a male brood pouch. This has contributed to a
      widespread, but poorly founded belief, that the eggs are fertilised using
      spermatozoa that are deposited directly into the brood pouch via an internal
      sperm duct. Anatomical dissections showed, however, not only that direct sperm
      deposition into the pouch is physically impossible, but that spermatozoa must
      somehow travel a significant distance (>4 mm) outside the body of the male, to
      reach and fertilise eggs in the pouch. Observations of courtship and mating
      behaviour also revealed that the pouch closes immediately after mating, and that
      sperm transfer must occur within a time window of no more than 6 s. In addition
      to this, the yellow seahorse produces extraordinarily low quantities of dimorphic
      spermatozoa, but is nevertheless highly fertile and can produce broods that
      exceed 100 embryos. The entire fertilisation process in seahorses is therefore
      uniquely efficient among vertebrates, yet paradoxically involves several steps
      that would seem to complicate, and even appear to prevent, the interaction of the
      gametes. Although we are still unable to describe the exact fertilisation
      mechanism, we speculate that spermatozoa are ejaculated into a mixture of ovarian
      fluid and eggs, while the male and female are in close contact. Thereafter, this
      mixture must enter the pouch, whereupon the spermatozoa encounter seawater. These
      observations also support the view, indirectly inferred in previous publications,
      that sperm competition in seahorses is not only non-existent but impossible.

PMID- 17234613
TI  - Cu2+ and acute thermal stress induce protective events via the p38-MAPK
      signalling pathway in the perfused Rana ridibunda heart.
AB  - In the present study, we investigated the induction of the p38-MAPK signalling
      pathway by copper, as exemplified by CuCl(2), in the isolated perfused heart of
      the amphibian Rana ridibunda. We found that p38-MAPK phosphorylation by CuCl(2)
      occurs in a dose-dependent manner, with maximum activation (8.73+/-1.43-fold
      relative to control values) attained by perfusion with 500 micromol l(-1) CuCl(2)
      for 15 min, while this activation sustained even after 60 min of reperfusion with
      normal bicarbonate buffer. CuCl(2) also induced the phosphorylation of the small
      heat shock protein 27 (Hsp27) in a p38-MAPK dependent manner, as revealed by
      experiments using the p38-MAPK inhibitor SB203580. p38-MAPK and Hsp27
      phosphorylations were also strongly induced by hyperthermia (42 degrees C), while
      the simultaneous use of hyperthermia and CuCl(2) had a synergistic effect on p38
      MAPK activation. Furthermore, perfusions with the potent antioxidant L-ascorbic
      acid (100 micromol l(-1)), the antioxidant enzymes catalase (CAT) (150 U ml(-1))
      or superoxide dismutase (SOD) (30 U ml(-1)) in the presence of 500 micromol l(-1)
      CuCl(2) did not attenuate the CuCl(2)-induced p38-MAPK activation, implying that
      at least the reactive oxygen species (ROS) scavenged by these agents are not
      implicated in this kinase activation. The p38-MAPK phosphorylation induced by the
      combined action of CuCl(2) and hyperthermia was partially inhibited by catalase,
      indicating that hyperthermia possibly activates the kinase through the production
      of H(2)O(2). Caspase-3, an effector protease of apoptosis, remained inactive in
      hearts perfused at normal or hyperthermic conditions, in the absence or presence
      of 500 micromol l(-1) CuCl(2). All the above results suggest that, in the
      amphibian Rana ridibunda heart, p38-MAPK activation by copper has a possible
      protective role through the small Hsp27.

PMID- 17234614
TI  - Spectral sensitivity of four species of fiddler crabs (Uca pugnax, Uca pugilator,
      Uca vomeris and Uca tangeri) measured by in situ microspectrophotometry.
AB  - Fiddler crabs have compound eyes that are structurally fairly well understood.
      However, there has been much debate regarding their spectral sensitivity and
      capacity to enable colour discrimination. We examined the visual pigments of two
      North-American species (Uca pugnax and U. pugilator), one species from the Indo
      West Pacific (U. vomeris) and the only Eastern-Atlantic species (U. tangeri) of
      fiddler crabs using in situ microspectrophotometry of frozen sections of dark
      adapted eyes. Only one spectral class of visual receptor was found in the larger
      (R1-7) retinular cells of each species, with maximum absorption peaking between
      508 nm and 530 nm (depending upon species). The R8 retinular cell, that might
      contain a short-wavelength sensitive photopigment and provide a basis for colour
      vision, was too small to analyze by these methods. Rhabdoms were lined with
      screening pigment which strongly influenced each species' spectral sensitivity,
      sharpening the peak and shifting the maximum towards longer wavelengths, on
      occasion to as far as the 600 nm region. We hypothesize that sensitivity to
      longer wavelengths enhances contrast between background (blue sky or tall
      vegetation) and the male major claw during the waving display.

PMID- 17234615
TI  - Excitable properties of adult skeletal muscle fibres from the honeybee Apis
      mellifera.
AB  - In the hive, a wide range of honeybees tasks such as cell cleaning, nursing,
      thermogenesis, flight, foraging and inter-individual communication (waggle dance,
      antennal contact and trophallaxy) depend on proper muscle activity. However,
      whereas extensive electrophysiological studies have been undertaken over the past
      ten years to characterize ionic currents underlying the physiological neuronal
      activity in honeybee, ionic currents underlying skeletal muscle fibre activity in
      this insect remain, so far, unexplored. Here, we show that, in contrast to many
      other insect species, action potentials in muscle fibres isolated from adult
      honeybee metathoracic tibia, are not graded but actual all-or-none responses.
      Action potentials are blocked by Cd(2+) and La(3+) but not by tetrodotoxin (TTX)
      in current-clamp mode of the patch-clamp technique, and as assessed under voltage
      clamp, both Ca(2+) and K(+) currents are involved in shaping action potentials in
      single muscle fibres. The activation threshold potential for the voltage
      dependent Ca(2+) current is close to -40 mV, its mean maximal amplitude is -8.5+/
      1.9 A/F and the mean apparent reversal potential is near +40 mV. In honeybees,
      GABA does not activate any ionic membrane currents in muscle fibres from the
      tibia, but L-glutamate, an excitatory neurotransmitter at the neuromuscular
      synapse induces fast activation of an inward current when the membrane potential
      is voltage clamped close to its resting value. Instead of undergoing
      desensitization as is the case in many other preparations, a component of this
      glutamate-activated current has a sustained component, the reversal potential of
      which is close to 0 mV, as demonstrated with voltage ramps. Future investigations
      will allow extensive pharmacological characterization of membrane ionic currents
      and excitation-contraction coupling in skeletal muscle from honeybee, a useful
      insect that became a model to study many physiological phenomena and which plays
      a major role in plant pollination and in stability of environmental vegetal
      biodiversity.

PMID- 17234616
TI  - Neuroethology of female preference in the synchronously singing bushcricket
      Mecopoda elongata (Tettigoniidae; Orthoptera): why do followers call at all?
AB  - Imperfect synchrony between male calls occurs in the acoustically interacting
      bushcricket Mecopoda elongata, and males establishing the temporal leadership
      attract more females in choice experiments. An asymmetrical representation of
      leader and follower signals in pairs of direction-selective neurons of the
      auditory pathway was suggested to represent the neural basis for the preference
      of females. We investigated the time-intensity trading effect, which occurs when
      the temporal advantage of the leader signal is compensated, and can be reversed,
      by an additional sound pressure level of the follower. In behavioural arena
      trials the intensity trading of the preference of females for leader signals
      depends on the playback level; a higher sound pressure level (SPL) is needed for
      compensation at higher playback levels. We studied the simultaneous neuronal
      representation of leader and follower signals, and the time-intensity trading
      function in the pair of omega-neurons in the CNS. Consistent with the behavioural
      data, the representation of leader and follower signals can be reversed with an
      additional loudness of the follower, and the steepness of the trading function
      depends on the playback level. We also implemented data on the neuronal
      representation of synchronized signals in individual receivers into computer
      based agents, which performed phonotaxis in a virtual sound field. Results of
      these simulations closely resemble those obtained from real females with respect
      to the overall preference under the various time-intensity trading conditions.
      Furthermore, in combination with the observed trading functions these simulations
      demonstrate, that under more realistic field conditions the ultimate success of
      followers in attracting females is much higher than suggested from arena trials.
      We discuss the evolutionary consequences for male calling strategies in
      synchronously calling Orthoptera.

PMID- 17234617
TI  - Effect of maternal myostatin antibody on offspring growth performance and body
      composition in mice.
AB  - Myostatin (GDF8) is a member of the transforming growth factor beta (TGF-beta)
      superfamily. The finding that animals with a knockout or mutation of the
      myostatin-encoding gene show increased muscle mass suggests that myostatin
      negatively regulates muscle growth. The study reported here was designed to
      investigate the effect of induction of maternal myostatin antibody on the growth
      performance and body composition of the mouse. Female mice were induced to
      produce myostatin antibody by immunization with synthetic myostatin peptide prior
      to mating with male mice. The body masses of offspring were measured weekly and
      the body compositions of offspring were determined at 8 weeks of age. The results
      showed that myostatin antibody was detected in both immunized female mice and
      their 8-week-old offspring. The growth performance of offspring from the
      myostatin antibody-induced (mstn Ab-induced) group was higher than that from the
      control group at 8 weeks of age. The body composition of both male and female
      offspring from the mstn Ab-induced group contained higher crude protein and lower
      crude fat than those from the control group (P<0.05). The litter number from the
      maternal mstn Ab-induced group was less than that from control mice, while embryo
      development was normal in both groups. However, the amount of developing follicle
      in ovaries of the mstn Ab-induced group was lower than that in the control group.
      It is concluded that induction of maternal mstn Ab enhances the growth
      performance of offspring and influences the offspring body composition by
      increasing the crude protein and reducing crude fat.

PMID- 17234618
TI  - Predicting the energy cost of terrestrial locomotion: a test of the LiMb model in
      humans and quadrupeds.
AB  - The energy cost of terrestrial locomotion has been linked to the muscle forces
      generated to support body weight and swing the limbs. The LiMb model predicts
      these forces, and hence locomotor cost, as a function of limb length and basic
      kinematic variables. Here, I test this model in humans, goats and dogs in order
      to assess the performance of the LiMb model in predicting locomotor cost for
      bipeds and quadrupeds. Model predictions were compared to observed locomotor
      cost, measured via oxygen consumption, during treadmill trials performed over a
      range of speeds for both walking and running gaits. The LiMb model explained more
      of the variation in locomotor cost than other predictors, including contact time,
      Froude number and body mass. The LiMb model also accurately predicted the
      magnitude of vertical ground forces. Results suggest the LiMb model reliably
      links locomotor anatomy to force production and locomotor cost. Further, these
      data support the idea that limb length may underlie the scaling of locomotor cost
      for terrestrial animals.

PMID- 17234619
TI  - Biting releases constraints on moray eel feeding kinematics.
AB  - We present an analysis of prey capture functional morphology in eels by comparing
      two species of moray eels, Muraena retifera and Echidna nebulosa (Family
      Muraenidae), to the American eel Anguilla rostrata (Family Anguillidae). The
      skulls of both moray species exhibited extreme reductions of several prominent
      components of the suction-feeding mechanism, including the hyoid bar, the
      sternohyoideus muscle and the pectoral girdle. Associated with these anatomical
      modifications, morays showed no evidence of using suction during prey capture.
      From 59 video sequences of morays feeding on pieces of cut squid we saw no hyoid
      depression and no movement of prey toward the mouth aperture during the strike, a
      widely used indicator of suction-induced water flow. This was in contrast to A.
      rostrata, which exhibited a robust hyoid, sternohyoideus muscle and pectoral
      girdle, and used suction to draw prey into its mouth. Average prey capture time
      in morays, about 500 ms, was roughly 10 times longer than in A. rostrata, and
      morays frequently reversed the direction of jaw and head rotation in the midst of
      the strike. We tested whether the absence of suction feeding reduces temporal
      constraints on feeding kinematics, permitting greater variance in traits that
      characterize timing and the extent of motion in the neurocranium, by comparing
      moray eel species with A. rostrata, two Centrarchids and a cichlid. Kinematic
      variance was roughly 5 times higher in morays than the suction-feeding species.
      Prey capture by suction demands a rapid, highly coordinated series of cranial
      movements and the loss of this mechanism appears to have permitted slower, more
      variable prey capture kinematics in morays. The alternative prey capture strategy
      in morays, biting, may be tied to their success as predators in the confined
      spaces of reef crevices where they hunt for cephalopods, crustaceans and fish.

PMID- 17234620
TI  - The directional hearing abilities of two species of bamboo sharks.
AB  - Auditory evoked potentials (AEPs) were used to measure the directional hearing
      thresholds of the white-spotted bamboo shark Chiloscyllium plagiosum and the
      brown-banded bamboo shark Chiloscyllium punctatum at four frequencies and seven
      directions, using a shaker table designed to mimic the particle motion component
      of sound. Over most directions and frequencies there were no significant
      differences in acceleration thresholds, suggesting that the sharks have omni
      directional hearing abilities. Goldfish Carassius auratus were used as a baseline
      to compare a species with specialized hearing adaptations versus sharks with no
      known adaptations, and were found to have more sensitive directional responses
      than the sharks. Composite audiograms of the sharks were created from the average
      of all of the directions at each frequency and were compared with an audiogram
      obtained for C. plagiosum using a dipole stimulus. The dipole stimulus audiograms
      were significantly lower at 50 and 200 Hz compared to the shaker audiograms in
      terms of particle acceleration. This difference is hypothesized to be a result of
      the dipole stimulating the macula neglecta, which would not be stimulated by the
      shaker table.

PMID- 17234621
TI  - Thermogenesis, food intake and serum leptin in cold-exposed lactating Brandt's
      voles Lasiopodomys brandtii.
AB  - Lactation is the most energetically expensive period for mammals and is
      associated with increased metabolism and energy intake, but decreased thermogenic
      capacity. It is well known that small mammals increase both food intake and
      thermogenesis in the cold. The present study aimed to examine whether Brandt's
      voles Lasiopodomys brandtii could adjust energy intake and thermogenesis to
      accommodate simultaneous lactation and cold exposure. The voles were placed into
      two temperature treatments: warm (23+/-1 degrees C) and cold (5+/-1 degrees C).
      Animals at each temperature treatment were further divided into two groups: non
      reproductive (NR) and lactating females. We found that lactating voles at peak
      lactation in the cold enhanced food intake by 2.6 g day(-1) compared with those
      in the warm, and increased uncoupling protein 1 (UCP1) content in brown adipose
      tissue (BAT), to the same level as the cold-exposed NR females. Serum leptin
      levels decreased significantly during lactation and were positively correlated
      with body mass and fat mass. After correcting for the effects of body mass,
      residual serum leptin was negatively correlated with residual gross energy intake
      and residual RMR. In addition, residual serum leptin levels were positively
      correlated with UCP1 contents in the warm, but not in the cold. Together, these
      data suggest that lactating voles can increase thermogenic capacity and energy
      intake to meet the high energetic costs of simultaneous lactation and cold
      exposure. Further, serum leptin appears to be involved in the energy intake
      regulation and thermoregulation, but the thermoregulation in the cold may be
      mainly mediated by other factors.

PMID- 17234622
TI  - The interaction of CO2 concentration and spatial location on O2 flux and mass
      transport in the freshwater macrophytes Vallisneria spiralis and V. americana.
AB  - The biology of aquatic organisms determines the maximum rates of physiological
      processes, but the mass transport of nutrients determines the nominal rates at
      which these processes occur. Maximum O(2) flux (P(max)) at 17.1 mmol m(-3) CO(2)
      was higher for the leaves of the freshwater macrophyte Vallisneria spiralis
      [P(max)=0.013+/-0.001 mmol m(-2) s(-1) (g(chla+b) m(-2))(-1) (mean +/- s.e.m.)]
      than for the closely related species, Vallisneria americana [P(max)=0.008+/-0.001
      mmol m(-2) s(-1) (g(chla+b) m(-2))(-1)]. The O(2) flux saturated at freestream
      velocities >4.5+/-1.2 cm s(-1) and was spatially invariant for both species.
      However, a tenfold decrease in CO concentration to 1.71 mmol m(-3) changed the
      nature of the relationship between O(2) flux and spatial location along the leaf
      surface, and reduced the O(2) flux of V. spiralis to values similar to V.
      americana. The O(2) flux [P(max)=0.007+/-0.001 mmol m(-2) s(-1) (g(chla+b) m(
      2))(-1)] saturated at the upstream location (i.e. 1 cm from the leading edge of
      the leaf) but was found to increase linearly with freestream velocity
      [slope=0.057+/-0.011 mmol m(-2) s(-1) (g(chla+b) m(-2))(-1) (m s(-1))(-1)] at the
      downstream location (i.e. 7 cm from the leading edge) at freestream velocities
      >1.8+/-0.9 cm s(-1). Conversely, mass transfer rates did not vary with CO(2)
      concentration, and were characteristic of a laminar concentration boundary layer
      at the upstream location and a turbulent concentration boundary layer at the
      downstream location. Rates of mass transfer measured directly from O(2) profiles
      were not predicted by theoretical values based on hydrodynamic measurements.
      Moreover, the concentration boundary layer thickness (delta(CBL)) values measured
      directly from O(2) profiles were 48+/-2% and 21+/-1% of the predicted theoretical
      delta(CBL) values at the upstream and downstream locations, respectively. It is
      evident that physiological processes involving mass transport are coupled and
      vary in space. Mass transport investigations of biological systems based solely
      on hydrodynamic measurements need to be interpreted with caution.

PMID- 17234623
TI  - Mechanics of dog walking compared with a passive, stiff-limbed, 4-bar linkage
      model, and their collisional implications.
AB  - Here, we present a simple stiff-limbed passive model of quadrupedal walking,
      compare mechanics predicted from the model with those observed from forceplate
      measurements of walking dogs and consider the implications of deviation from
      model predictions, especially with reference to collision mechanics. The model is
      based on the geometry of a 4-bar linkage consisting of a stiff hindleg, back,
      foreleg and the ground between the hind and front feet. It uses empirical
      morphological and kinematic inputs to determine the fluctuations in potential and
      kinetic energy, vertical and horizontal forces and energy losses associated with
      inelastic collisions at each foot placement. Using forceplate measurements to
      calculate centre of mass motions of walking dogs, we find that (1) dogs may, but
      are not required to, spend periods of double support (one hind- and one forefoot)
      agreeing with the passive model; (2) legs are somewhat compliant, and mechanical
      energy fluctuates during triple support, with mechanical energy being lost
      directly after hindfoot placement and replaced following forefoot placement.
      Footfall timings and timing of mechanical energy fluctuations are consistent with
      strategies to reduce collisional forces, analogous to the suggested role of ankle
      extension as an efficient powering mechanism in human walking.

PMID- 17234624
TI  - Trimethylamine oxide suppresses stress-induced alteration of organic anion
      transport in choroid plexus.
AB  - The effect of physicochemical stress on organic anion transport across the
      vertebrate blood-cerebrospinal fluid (CSF) barrier in the presence and absence of
      an endogenous cytoprotectant, trimethylamine oxide (TMAO), was investigated in
      isolated IVth choroid plexus (CP) of spiny dogfish shark (Squalus acanthias), an
      animal with naturally high levels of TMAO ( approximately 70 mmol l(-1)). Active
      transepithelial absorption of the organic anion, 2,4-dichlorophenoxyacetic acid
      (2,4-D), by IVth CP mounted in Ussing chambers was measured after in vitro
      stress, and a marker for the cellular stress response, inducible heat shock
      protein 70 (Hsp70), was assayed by immunoblot analysis. Transient heat stress (a
      shift from the normal 13.5 degrees C to 23.5 degrees C for 1 h) decreased 2,4-D
      transport by approximately 66%; however, the same stress minus TMAO (isosmotic
      replacement with urea) had no effect on transport rate. In the absence of TMAO,
      stress-induced Hsp70 accumulation was more than double that seen in the presence
      of TMAO. Likewise, exposure to 50 micromol l(-1) Zn for 6 h induced a twofold
      greater Hsp70 accumulation in the absence of TMAO than in its presence, and the
      higher Hsp70 level was associated with a higher 2,4-D transport rate. Heat stress
      and 50 micromol l(-1) Zn also induced more pronounced increases in Hsp70 mRNA in
      the absence of TMAO. Thus, the cellular stress response can significantly alter
      CP organic anion transport capacity, and an endogenous osmolyte can suppress that
      response.

PMID- 17234625
TI  - Low serum vitamin B12 in older people: the role of alcohol and thyroid status.

PMID- 17234626
TI  - Training in geriatric medicine in UK undergraduate medical schools.

PMID- 17234627
TI  - RhoA/Rho kinase up-regulate Bax to activate a mitochondrial death pathway and
      induce cardiomyocyte apoptosis.
AB  - The small G-protein RhoA regulates the actin cytoskeleton, and its involvement in
      cell proliferation has also been established. In contrast, little is known about
      whether RhoA participates in cell survival or apoptosis. In cardiomyocytes in
      vitro, RhoA induces hypertrophic cell growth and gene expression. In vivo,
      however, RhoA expression leads to development of heart failure (Sah, V. P.,
      Minamisawa, S., Tam, S. P., Wu, T. H., Dorn, G. W., Ross, J. Jr., Chien, K. R.,
      and Brown, J. H. (1999) J. Clin. Investig. 103, 1627-1634), a condition widely
      associated with cardiomyocyte apoptosis. We demonstrate here that adenoviral
      overexpression of activated RhoA in cardiomyocytes induces hypertrophy, which
      transitions over time to apoptosis, as evidenced by caspase activation and
      nucleosomal DNA fragmentation. The Rho kinase inhibitors Y-27632 and HA-1077 and
      expression of a dominant negative Rho kinase block these responses. Caspase-9,
      but not caspase-8, is activated, and its inhibition prevents DNA fragmentation,
      consistent with involvement of a mitochondrial death pathway. Interestingly, RhoA
      expression induces a 3-4-fold up-regulation of the proapoptotic Bcl-2 family
      protein Bax. RhoA also increases levels of activated Bax and the amount of Bax
      protein localized at mitochondria. Bax mRNA is increased by RhoA, indicating
      transcriptional regulation, and the ability of a dominant negative p53 mutant to
      block Bax up-regulation implicates p53 in this response. The involvement of Bax
      in RhoA-induced apoptosis was examined by treatment with a Bax-inhibitory
      peptide, which was found to significantly attenuate DNA fragmentation and caspase
      9 and -3 activation. The dominant negative p53 also prevents RhoA-induced
      apoptosis. We conclude that RhoA/Rho kinase activation up-regulates Bax through
      p53 to induce a mitochondrial death pathway and cardiomyocyte apoptosis.

PMID- 17234628
TI  - The core histone tail domains contribute to sequence-dependent nucleosome
      positioning.
AB  - The precise positioning of nucleosomes plays a critical role in the regulation of
      gene expression by modulating the DNA binding activity of trans-acting factors.
      However, molecular determinants responsible for positioning are not well
      understood. We examined whether the removal of the core histone tail domains from
      nucleosomes reconstituted with specific DNA fragments led to alteration of
      translational positions. Remarkably, we find that removal of tail domains from a
      nucleosome assembled on a DNA fragment containing a Xenopus borealis somatic-type
      5S RNA gene results in repositioning of nucleosomes along the DNA, including two
      related major translational positions that move about 20 bp further upstream with
      respect to the 5S gene. In a nucleosome reconstituted with a DNA fragment
      containing the promoter of a Drosophila alcohol dehydrogenase gene, several
      translational positions shifted by about 10 bp along the DNA upon tail removal.
      However, the positions of nucleosomes assembled with a DNA fragment known to have
      one of the highest binding affinities for core histone proteins in the mouse
      genome were not altered by removal of core histone tail domains. Our data support
      the notion that the basic tail domains bind to nucleosomal DNA and influence the
      selection of the translational position of nucleosomes and that once tails are
      removed movement between translational positions occurs in a facile manner on
      some sequences. However, the effect of the N-terminal tails on the positioning
      and movement of a nucleosome appears to be dependent on the DNA sequence such
      that the contribution of the tails can be masked by very high affinity DNA
      sequences. Our results suggest a mechanism whereby sequence-dependent nucleosome
      positioning can be specifically altered by regulated changes in histone tail-DNA
      interactions in chromatin.

PMID- 17234629
TI  - In vitro analysis of SpUre2p, a prion-related protein, exemplifies the
      relationship between amyloid and prion.
AB  - The yeast Saccharomyces cerevisiae contains in its proteome at least three prion
      proteins. These proteins (Ure2p, Sup35p, and Rnq1p) share a set of remarkable
      properties. In vivo, they form aggregates that self-perpetuate their aggregation.
      This aggregation is controlled by Hsp104, which plays a major role in the growth
      and severing of these prions. In vitro, these prion proteins form amyloid fibrils
      spontaneously. The introduction of such fibrils made from Ure2p or Sup35p into
      yeast cells leads to the prion phenotypes [URE3] and [PSI], respectively.
      Previous studies on evolutionary biology of yeast prions have clearly established
      that [URE3] is not well conserved in the hemiascomycetous yeasts and particularly
      in S. paradoxus. Here we demonstrated that the S. paradoxus Ure2p is able to form
      infectious amyloid. These fibrils are more resistant than S. cerevisiae Ure2p
      fibrils to shear force. The observation, in vivo, of a distinct aggregation
      pattern for GFP fusions confirms the higher propensity of SpUre2p to form
      fibrillar structures. Our in vitro and in vivo analysis of aggregation propensity
      of the S. paradoxus Ure2p provides an explanation for its loss of infective
      properties and suggests that this protein belongs to the non-prion amyloid world.

PMID- 17234630
TI  - Sloppy bypass of an abasic lesion catalyzed by a Y-family DNA polymerase.
AB  - DNA damage that eludes cellular repair pathways can arrest the replication
      machinery and stall the cell cycle. However, this damage can be bypassed by the Y
      family DNA polymerases. Here, Dpo4, an archetypal Y-family member from the
      thermophilic Sulfolobus solfataricus, was used to extend our kinetic studies of
      the bypass of an abasic site, one of the most mutagenic and ubiquitous cellular
      lesions. A short oligonucleotide sequencing assay is developed to directly
      sequence DNA bypass products synthesized by Dpo4. Our results show that
      incorporation upstream of the abasic lesion is replicated error-free; yet
      dramatically, once Dpo4 encounters the lesion, synthesis became sloppy, with
      bypass products containing a myriad of mutagenic events. Incorporation of dAMP
      (29%) and dCMP (53%) opposite the abasic lesion at 37 degrees C correlates
      exceptionally well with our kinetic results and demonstrates two dominant bypass
      pathways via the A-rule and the lesion loop-out mechanism. Interestingly, the
      percentage of overall frameshift mutations increased from 71 (37 degrees C) to
      87% (75 degrees C). Further analysis indicates that lesion bypass via the A-rule
      is strongly preferred over the lesion loop-out mechanism at higher temperatures
      and concomitantly reduces the occurrence of "-1 deletion" mutations observed
      opposite the lesion at lower temperatures. The bypass percentage via the latter
      pathway is confirmed by an enzymatic digestion assay, verifying the reliability
      of our sequencing assay. Our results demonstrate that an abasic lesion causes
      Dpo4 and possibly all Y-family members to switch from a normal to a very
      mutagenic mode of replication.

PMID- 17234631
TI  - Apolipoprotein E4 in macrophages enhances atherogenesis in a low density
      lipoprotein receptor-dependent manner.
AB  - Apolipoprotein E (apoE) and the low density lipoprotein receptor (LDLr) are well
      recognized determinants of atherosclerosis. In addition to hepatocytes, where
      both are highly expressed and contribute to plasma lipoprotein clearance, they
      are expressed in vascular cells and macrophages. In this study, we examined the
      effects of human apoE isoforms and LDLr levels in atherogenic pathways in primary
      macrophages ex vivo and atherosclerosis development after bone marrow transfer in
      vivo using mice expressing human apoE isoforms and different levels of LDLr
      expression. Increases in LDLr expression significantly increased cholesterol
      delivery into macrophages in culture, and the effects were more prominent with
      lipoproteins containing apoE4 than those containing apoE3. Conversely, increased
      LDLr expression reduced cholesterol efflux in macrophages expressing apoE4 but
      not in macrophages expressing apoE3. Furthermore, apoE3 protected VLDL from
      oxidation in vitro more than did apoE4. In LDLr-deficient mice expressing the
      human apoE4 isoform, Apoe4/4 Ldlr-/-, the replacement of bone marrow cells with
      those expressing LDLr increased atherosclerotic lesions in a dose-dependent
      manner compared with mice transplanted with cells having no LDLr. In contrast,
      atherosclerosis in Apoe3/3 Ldlr-/- mice, expressing the human apoE3 isoform, did
      not differ by the levels of macrophage LDLr expression. Our results demonstrate
      that apoE4, but not apoE3, in macrophages enhances atherosclerotic plaque
      development in mice in an LDLr-dependent manner and suggests that this
      interaction may contribute to the association of apoE4 with an increased
      cardiovascular risk in humans.

PMID- 17234632
TI  - Splice variants of the human zinc transporter ZnT5 (SLC30A5) are differentially
      localized and regulated by zinc through transcription and mRNA stability.
AB  - Maintenance of cellular zinc homeostasis includes regulating the expression of
      cell membrane zinc transporters. Knowledge about the mechanisms underlying
      changes in mammalian zinc transporter mRNA abundance is poor. We demonstrated
      that when expressed in Chinese hamster ovary cells as N-terminal fusions to green
      fluorescent protein, two splice variants of ZnT5 adopt different subcellular
      locations (either in the Golgi apparatus or throughout the cell, including at the
      plasma membrane) indicating discrete roles in cellular zinc homeostasis. We
      demonstrated, using a beta-galactosidase reporter gene, that both splice variants
      were expressed from a promoter region that was transcriptionally repressed by
      increased extracellular zinc (150 microM compared with 3 mum; approximately 40%)
      and by extracellular zinc depletion, using the chelator N,N,N',N'-tetrakis(2
      pyridylmethyl) ethylenediamine ( approximately 20%). We mapped the zinc
      responsive element to the region -154 to +50, relative to the predicted start of
      transcription, and showed that a consensus metal response element sequence (-410
      to -404) was not responsible for these effects. Changes in ZnT5 mRNA abundance in
      Caco-2 cells at different zinc concentrations were in parallel to the changes in
      promoter activity ( approximately 40% reduction at 150 microM zinc) but in the
      presence of actinomycin D, to prevent transcription, we observed a marked
      stabilization (1.7-2-fold accumulation over 24 h) of ZnT5 mRNA. We conclude that
      effects of zinc on ZnT5 transcription and mRNA stability act in opposition to
      balance mRNA abundance for cellular zinc homeostasis. To our knowledge, this is
      the first report that zinc affects the stability of a transcript with a direct
      role in cellular zinc homeostasis.

PMID- 17234633
TI  - Aqueous access pathways in ATP synthase subunit a. Reactivity of cysteine
      substituted into transmembrane helices 1, 3, and 5.
AB  - Subunit a is thought to play a key role in H+ transport-driven rotation of the
      subunit c ring in Escherichia coli F1F0 ATP synthase. In the membrane-traversing
      F0 sector of the enzyme, H+ binding and release occurs at Asp-61 in the middle of
      the second transmembrane helix (TMH) of subunit c. Protons are thought to reach
      Asp-61 via aqueous channels formed at least in part by one or more of the five
      TMHs of subunit a. Aqueous access to surfaces of TMHs 2, 4, and 5 was previously
      suggested based upon the chemical reactivity of cysteine residues substituted
      into these helices. Here we have substituted Cys into TMH1 and TMH3 and extended
      the substitutions in TMH5 to the cytoplasmic surface. One region of TMH3 proved
      to be moderately Ag+-sensitive and may connect with the Ag+-sensitive region
      found previously on the periplasmic side of TMH2. A single Cys substitution in
      TMH1 proved to be both N-ethylmaleimide (NEM)-sensitive and Ag+-sensitive and
      suggests a possible packing interaction of TMH1 with TMH2 and TMH3. New Ag+- and
      NEM-sensitive residues were found at the cytoplasmic end of TMH5 and suggest a
      possible connection of this region to the NEM- and Ag+-sensitive region of TMH4
      described previously. From the now complete pattern of TMH residue reactivity, we
      conclude that aqueous access from the periplasmic side of F0 to cAsp-61 at the
      center of the membrane is likely to be mediated by residues of TMHs 2, 3, 4, and
      5 at the center of a four-helix bundle. Further, aqueous access between cAsp-61
      and the cytoplasmic surface is likely to be mediated by residues in TMH4 and TMH5
      at the exterior of the four-helix bundle that are in contact with the c-ring.

PMID- 17234634
TI  - The c-Myc target gene Rcl (C6orf108) encodes a novel enzyme, deoxynucleoside 5'
      monophosphate N-glycosidase.
AB  - RCL is a c-Myc target with tumorigenic potential. Genome annotation predicted
      that RCL belonged to the N-deoxyribosyltransferase family. However, its putative
      relationship to this class of enzymes did not lead to its precise biochemical
      function. The purified native or N-terminal His-tagged recombinant rat RCL
      protein expressed in Escherichia coli exhibits the same enzyme activity,
      deoxynucleoside 5'-monophosphate N-glycosidase, never before described. dGMP
      appears to be the best substrate. RCL opens a new route in the nucleotide
      catabolic pathways by cleaving the N-glycosidic bond of deoxynucleoside 5'
      monophosphates to yield two reaction products, deoxyribose 5-phosphate and purine
      or pyrimidine base. Biochemical studies show marked differences in the terms of
      the structure and catalytic mechanism between RCL and of its closest enzyme
      family neighbor, N-deoxyribosyltransferase. The reaction products of this novel
      enzyme activity have been implicated in purine or pyrimidine salvage, glycolysis,
      and angiogenesis, and hence are all highly relevant for tumorigenesis.

PMID- 17234635
TI  - Diploids heterozygous for a vma13Delta mutation in Saccharomyces cerevisiae
      highlight the importance of V-ATPase subunit balance in supporting vacuolar
      acidification and silencing cytosolic V1-ATPase activity.
AB  - The V-ATPase H subunit (encoded by the VMA13 gene) activates ATP-driven proton
      pumping in intact V-ATPase complexes and inhibits MgATPase activity in cytosolic
      V1 sectors (Parra, K. J., Keenan, K. L., and Kane, P. M. (2000) J. Biol. Chem.
      275, 21761-21767). Yeast diploids heterozygous for a vma13Delta mutation show the
      pH- and calcium-dependent conditional lethality characteristic of mutants lacking
      V-ATPase activity, although they still contain one wild-type copy of VMA13.
      Vacuolar vesicles from this strain have approximately 50% of the ATPase activity
      of those from a wild-type diploid but do not support formation of a proton
      gradient. Compound heterozygotes with a second heterozygous deletion in another
      V1 subunit gene exhibit improved growth, vacuolar acidification, and ATP-driven
      proton transport in vacuolar vesicles. In contrast, compound heterozygotes with a
      second deletion in a Vo subunit grow even more poorly than the vma13Delta
      heterozygote, have very little vacuolar acidification, and have very low levels
      of V-ATPase subunits in isolated vacuoles. In addition, cytosolic V1 sectors from
      this strain and from the strain containing only the heterozygous vma13Delta
      mutation have elevated MgATPase activity. The results suggest that balancing
      levels of subunit H with those of other V-ATPase subunits is critical, both for
      allowing organelle acidification and for preventing unproductive hydrolysis of
      cytosolic ATP.

PMID- 17234636
TI  - Protein-protein interaction site prediction based on conditional random fields.
AB  - MOTIVATION: We are motivated by the fast-growing number of protein structures in
      the Protein Data Bank with necessary information for prediction of protein
      protein interaction sites to develop methods for identification of residues
      participating in protein-protein interactions. We would like to compare
      conditional random fields (CRFs)-based method with conventional classification
      based methods that omit the relation between two labels of neighboring residues
      to show the advantages of CRFs-based method in predicting protein-protein
      interaction sites. RESULTS: The prediction of protein-protein interaction sites
      is solved as a sequential labeling problem by applying CRFs with features
      including protein sequence profile and residue accessible surface area. The CRFs
      based method can achieve a comparable performance with state-of-the-art methods,
      when 1276 nonredundant hetero-complex protein chains are used as training and
      test set. Experimental result shows that CRFs-based method is a powerful and
      robust protein-protein interaction site prediction method and can be used to
      guide biologists to make specific experiments on proteins. AVAILABILITY:
      http://www.insun.hit.edu.cn/~mhli/site_CRFs/index.html. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 17234637
TI  - snp.plotter: an R-based SNP/haplotype association and linkage disequilibrium
      plotting package.
AB  - snp.plotter is a newly developed R package which produces high-quality plots of
      results from genetic association studies. The main features of the package
      include options to display a linkage disequilibrium (LD) plot below the P-value
      plot using either the r2 or D' LD metric, to set the X-axis to equal spacing or
      to use the physical map of markers, and to specify plot labels, colors, symbols
      and LD heatmap color scheme. snp.plotter can plot single SNP and/or haplotype
      data and simultaneously plot multiple sets of results. R is a free software
      environment for statistical computing and graphics available for most platforms.
      The proposed package provides a simple way to convey both association and LD
      information in a single appealing graphic for genetic association studies.
      AVAILABILITY: Downloadable R package and example datasets are available at
      http://cbdb.nimh.nih.gov/~kristin/snp.plotter.html and http://www.r-project.org.

PMID- 17234638
TI  - A structural alignment kernel for protein structures.
AB  - MOTIVATION: This work aims to develop computational methods to annotate protein
      structures in an automated fashion. We employ a support vector machine (SVM)
      classifier to map from a given class of structures to their corresponding
      structural (SCOP) or functional (Gene Ontology) annotation. In particular, we
      build upon recent work describing various kernels for protein structures, where a
      kernel is a similarity function that the classifier uses to compare pairs of
      structures. RESULTS: We describe a kernel that is derived in a straightforward
      fashion from an existing structural alignment program, MAMMOTH. We find in our
      benchmark experiments that this kernel significantly out-performs a variety of
      other kernels, including several previously described kernels. Furthermore, in
      both benchmarks, classifying structures using MAMMOTH alone does not work as well
      as using an SVM with the MAMMOTH kernel. AVAILABILITY:
      http://noble.gs.washington.edu/proj/3dkernel

PMID- 17234639
TI  - Deleterious SNP prediction: be mindful of your training data!
AB  - MOTIVATION: To predict which of the vast number of human single nucleotide
      polymorphisms (SNPs) are deleterious to gene function or likely to be disease
      associated is an important problem, and many methods have been reported in the
      literature. All methods require data sets of mutations classified as
      'deleterious' or 'neutral' for training and/or validation. While different
      workers have used different data sets there has been no study of which is best.
      Here, the three most commonly used data sets are analysed. We examine their
      contents and relate this to classifiers, with the aims of revealing the strengths
      and pitfalls of each data set, and recommending a best approach for future
      studies. RESULTS: The data sets examined are shown to be substantially different
      in content, particularly with regard to amino acid substitutions, reflecting the
      different ways in which they are derived. This leads to differences in
      classifiers and reveals some serious pitfalls of some data sets, making them less
      than ideal for non-synonymous SNP prediction. AVAILABILITY: Software is available
      on request from the authors.

PMID- 17234640
TI  - Nested Containment List (NCList): a new algorithm for accelerating interval query
      of genome alignment and interval databases.
AB  - MOTIVATION: The exponential growth of sequence databases poses a major challenge
      to bioinformatics tools for querying alignment and annotation databases. There is
      a pressing need for methods for finding overlapping sequence intervals that are
      highly scalable to database size, query interval size, result size and
      construction/updating of the interval database. RESULTS: We have developed a new
      interval database representation, the Nested Containment List (NCList), whose
      query time is O(n + log N), where N is the database size and n is the size of the
      result set. In all cases tested, this query algorithm is 5-500-fold faster than
      other indexing methods tested in this study, such as MySQL multi-column indexing,
      MySQL binning and R-Tree indexing. We provide performance comparisons both in
      simulated datasets and real-world genome alignment databases, across a wide range
      of database sizes and query interval widths. We also present an in-place NCList
      construction algorithm that yields database construction times that are
      approximately 100-fold faster than other methods available. The NCList data
      structure appears to provide a useful foundation for highly scalable interval
      database applications. AVAILABILITY: NCList data structure is part of Pygr, a
      bioinformatics graph database library, available at
      http://sourceforge.net/projects/pygr

PMID- 17234641
TI  - CoCo: a web application to display, store and curate ChIP-on-chip data integrated
      with diverse types of gene expression data.
AB  - MOTIVATION: CoCo, ChIP-on-Chip online, is an open-source web application that
      supports the annotation and curation of regulatory regions and associated target
      genes discovered in ChIP-on-chip experiments. CoCo integrates ChIP-on-chip
      results with diverse types of gene expression data (expression profiling, in situ
      hybridization) and displays them within a genomic context. Regulatory
      relationships between the transcription factor-bound regions and putative target
      genes can be stored and expanded throughout different sessions. AVAILABILITY:
      http://furlonglab.embl.de/methods/tools/coco.

PMID- 17234642
TI  - TreeQ-VISTA: an interactive tree visualization tool with functional annotation
      query capabilities.
AB  - We describe a general multiplatform exploratory tool called TreeQ-Vista, designed
      for presenting functional annotations in a phylogenetic context. Traits, such as
      phenotypic and genomic properties, are interactively queried from a user-provided
      relational database with a user-friendly interface which provides a set of tools
      for users with or without SQL knowledge. The query results are projected onto a
      phylogenetic tree and can be displayed in multiple color groups. A rich set of
      browsing, grouping and query tools are provided to facilitate trait exploration,
      comparison and analysis. AVAILABILITY: The program, detailed tutorial and
      examples are available online (http:/genome.lbl.gov/vista/TreeQVista).

PMID- 17234643
TI  - A faster circular binary segmentation algorithm for the analysis of array CGH
      data.
AB  - MOTIVATION: Array CGH technologies enable the simultaneous measurement of DNA
      copy number for thousands of sites on a genome. We developed the circular binary
      segmentation (CBS) algorithm to divide the genome into regions of equal copy
      number. The algorithm tests for change-points using a maximal t-statistic with a
      permutation reference distribution to obtain the corresponding P-value. The
      number of computations required for the maximal test statistic is O(N2), where N
      is the number of markers. This makes the full permutation approach
      computationally prohibitive for the newer arrays that contain tens of thousands
      markers and highlights the need for a faster algorithm. RESULTS: We present a
      hybrid approach to obtain the P-value of the test statistic in linear time. We
      also introduce a rule for stopping early when there is strong evidence for the
      presence of a change. We show through simulations that the hybrid approach
      provides a substantial gain in speed with only a negligible loss in accuracy and
      that the stopping rule further increases speed. We also present the analyses of
      array CGH data from breast cancer cell lines to show the impact of the new
      approaches on the analysis of real data. AVAILABILITY: An R version of the CBS
      algorithm has been implemented in the "DNAcopy" package of the Bioconductor
      project. The proposed hybrid method for the P-value is available in version 1.2.1
      or higher and the stopping rule for declaring a change early is available in
      version 1.5.1 or higher.

PMID- 17234644
TI  - Enhancement of chromosomal aberrations in tumor cells with a non-labeled Cu-PTSM
      and irradiation with Cu K-shell monochromatic X rays.
AB  - This study aims to clarify the enhancement effect on chromosomal aberrations via
      selective energy absorption by Cu atoms in cultured bone cancer cells with non
      labelled Cu-pyruvaldehyde-bis(N(4)-methylsemicarbazone) (Cu-PTSM) and
      monochromatic X rays. The X rays having the energy of the Cu K-shell absorption
      edge arising from synchrotron radiation (KEK-PF) was used as radiation source. Cu
      PTSM labelled with copper radionuclides has been developed for medical imaging
      using positron emission tomography (PET). Evidence clearly showed that the
      absorption of X rays in the Cu K-shell caused this enhancement. After cells were
      treated with 1000 nM Cu-PTSM, the enhancement ratio of the initial yield of
      isochromatid breaks caused by CuK-H X-ray irradiation to that by 200 kV(p) X rays
      was approximately 2.8. About 5.6 times of the remaining isochromatid breaks were
      observed at 4 h in Cu-PTSM treated samples irradiated with CuK-H X rays comparing
      to that with 200 kV(p) X rays. In this study, uniqueness in physical property
      such as Cu atom K-shell ionisation was applied for the enhancement of biological
      effects in cancer cells.

PMID- 17234645
TI  - The effects of dose, route, and repeated dosing on the disposition and kinetics
      of tetrabromobisphenol A in male F-344 rats.
AB  - Studies were conducted to characterize the metabolic and dispositional fate of
      (14)C-tetrabromobisphenol A (TBBPA)-a commonly used brominated flame retardant,
      in male Fischer-344 rats. The percent of dose eliminated as total radioactivity
      in feces at 72 h following three different single oral doses (2, 20, or 200
      mg/kg) of (14)C-TBBPA was 90% or greater for all doses. Most of the dose was
      eliminated in the first 24 h. At 72 h after administration of the highest dose,
      the amounts of (14)C found in the tissues were minimal (0.2-0.9%). With repeated
      daily oral doses (20 mg/kg) for 5 or 10 days, the cumulative percent dose
      eliminated in the feces was 85.1+/-2.8 and 97.9+/-1.1, respectively. In all
      studies radioactivity recovered in urine was minimal, <2%. Repeated dosing did
      not lead to retention in tissues. Following iv administration, feces was also the
      major route of elimination. Following iv administration of TBBPA, the radiolabel
      found in the blood decreased rapidly and could be described by a biexponential
      equation, consistent with a two-compartment model. The key calculated kinetic
      parameters are terminal elimination half-life (t(1/2)beta)=82 min; area under the
      blood concentration-time curve from time 0 to infinity (AUC)=1440 mug x min/ml;
      and apparent clearance (CL)=2.44 ml/min. Although readily absorbed from the gut,
      systemic bioavailability of TBBPA is low (<2%). It is extensively extracted and
      metabolized by the liver and the metabolites (glucuronides) exported into the
      bile. About 50% of an oral dose (20 mg/kg) was found in the bile within 2 h. This
      extensive extraction and metabolism by the liver greatly limits exposure of
      internal tissues to TBBPA following oral exposures.

PMID- 17234646
TI  - Can exposure characterization explain concurrence or discordance between
      toxicology and epidemiology?
AB  - The importance of reliable exposure assessment, as a key component of the overall
      risk assessment process, has been well described for some considerable time. Yet,
      despite this widely accepted tenet, many studies conclude significant adverse
      health effects, with associated public policy implications, in the absence of
      adequate or, in some cases, even rudimentary, exposure quantification. Moreover,
      it appears that epidemiological studies in humans and toxicological studies in
      experimental animals may both suffer from inadequate exposure assessment. In this
      review, we discuss the nature and quality of the exposure assessment in both
      epidemiologic and toxicologic studies using examples from the pesticides and
      phthalate literature. Each type of study has its strengths and weaknesses in how
      exposure is assessed and often the strength of one is also a weakness. It would
      appear that insufficient or incomplete information about differences in exposure
      assessment could explain, at least in some cases, the differences in outcome
      between toxicological and epidemiological studies. Research efforts should focus
      on improving the feasibility of including biomonitoring in both animal and human
      studies to facilitate comparisons between animal and human models and improve
      exposure assessment in epidemiologic studies. Animal and human studies should
      measure the same biomarkers, where possible, to facilitate human health risk
      assessment.

PMID- 17234647
TI  - Prochloraz inhibits testosterone production at dosages below those that affect
      androgen-dependent organ weights or the onset of puberty in the male Sprague
      Dawley rat.
AB  - Prochloraz (PCZ) is an imidazole fungicide that inhibits gonadal steroidogenesis
      and antagonizes the androgen receptor (AR). We hypothesized that pubertal
      exposure to PCZ would reduce testosterone production and delay male rat
      reproductive development. Sprague Dawley rats were dosed by gavage with 0, 31.3,
      62.5, or 125 mg/kg/day of PCZ from postnatal day (PND) 23 to 42 or 51. There was
      a significant delay in preputial separation (PPS) at 125 mg/kg/day PCZ and
      several of the androgen-dependent organ weights were decreased significantly, but
      the significant organ weight effects were not consistent between the 2 necropsies
      (PND 42 vs. 51). At both ages, serum testosterone levels and ex vivo testosterone
      release from the testis were significantly decreased whereas serum progesterone
      and 17alpha-hydroxyprogesterone levels were significantly increased at dose
      levels below those that affected PPS or reproductive organ weights. The hormone
      results suggested that PCZ was inhibiting CYP17 activity. In a second pubertal
      study (0, 3.9, 7.8, 15.6, 31.3, or 62.5 mg/kg/day PCZ), serum testosterone levels
      and ex vivo testosterone production were significantly reduced at 15.6 mg/kg/day
      PCZ. In order to examine the AR antagonism effects of PCZ, independent of its
      effects on testosterone synthesis, castrated immature male rats were dosed with
      androgen and 0, 15.6, 31.3, 62.5, or 125 mg/kg/day PCZ for 10-11 days
      (Hershberger assay). In this assay, androgen-sensitive organ weights were only
      significantly decreased at 125 mg/kg/day PCZ. These data from the pubertal assays
      demonstrate that PCZ decreases testosterone levels and delays rat pubertal
      development, as hypothesized. However, the fact that hormone levels were affected
      at dosage eightfold below that which delayed the onset of puberty suggests that
      rather large reductions in serum testosterone may be required to delay puberty
      and consistently reduce androgen-dependent tissue weights.

PMID- 17234648
TI  - Expression of zebra fish aromatase cyp19a and cyp19b genes in response to the
      ligands of estrogen receptor and aryl hydrocarbon receptor.
AB  - Many endocrine-disrupting chemicals act via estrogen receptor (ER) or aryl
      hydrocarbon receptor (AhR). To investigate the interference between ER and AhR,
      we studied the effects of 17beta-estradiol (E2) and 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD) on the expression of zebra fish cyp19a (zfcyp19a) and cyp19b
      (zfcyp19b) genes, encoding aromatase P450, an important steroidogenic enzyme. In
      vivo (mRNA quantification in exposed zebra fish larvae) and in vitro (activity of
      zfcyp19-luciferase reporter genes in cell cultures in response to chemicals and
      zebra fish transcription factors) assays were used. None of the treatments
      affected zfcyp19a, excluding the slight upregulation by E2 observed in vitro.
      Strong upregulation of zfcyp19b by E2 in both assays was downregulated by TCDD.
      This effect could be rescued by the addition of an AhR antagonist. Antiestrogenic
      effect of TCDD on the zfcyp19b expression in the brain was also observed on the
      protein level, assessed by immunohistochemistry. TCDD alone did not affect
      zfcyp19b expression in vivo or promoter activity in the presence of zebra fish
      AhR2 and AhR nuclear translocator 2b (ARNT2b) in vitro. However, in the presence
      of zebra fish ERalpha, AhR2, and ARNT2b, TCDD led to a slight upregulation of
      promoter activity, which was eliminated by either an ER or AhR antagonist.
      Studies with mutated reporter gene constructs indicated that both mechanisms of
      TCDD action in vitro were independent of dioxin-responsive elements (DREs)
      predicted in the promoter. This study shows the usefulness of in vivo zebra fish
      larvae and in vitro zfcyp19b reporter gene assays for evaluation of estrogenic
      chemical actions, provides data on the functionality of DREs predicted in zfcyp19
      promoters and shows the effects of cross talk between ER and AhR on zfcyp19b
      expression. The antiestrogenic effect of TCDD demonstrated raises further
      concerns about the neuroendocrine effects of AhR ligands.

PMID- 17234649
TI  - The EUSTAR model for teaching and implementing the modified Rodnan skin score in
      systemic sclerosis.
AB  - OBJECTIVE: To evaluate the ability to teach scleroderma experts and young
      rheumatologists to perform the modified Rodnan skin score test. METHODS: Three
      international "teaching courses for teachers" were conducted with 6-9 experts who
      performed 3-9 skin score tests each. In addition, an international course for 90
      young rheumatologists, in which 18 patients with systemic sclerosis (SSc)
      participated, was also organised. Finally, a local repeated training course for 5
      9 rheumatologists was performed, in which 6-7 patients with SSc participated.
      RESULTS: When 6-9 scleroderma specialists investigated the patients, the
      intraclass correlation coefficient (ICC) showed "good" to "excellent" values
      (0.865 and 0.710, respectively). When 90 young rheumatologists were involved in
      one teaching course, the coefficient of variation (CV) was relatively
      satisfactory (35%) owing to the high number of investigators, and with a
      considerable within-patient SD value of 5.4. Repeated teaching of 5-9 young
      rheumatologists in local courses clearly improved the consistency. The ICC
      increased from 0.496 to a "good" level of 0.722. The within-patient SD values for
      intraobserver variability ranged between 2.5 and 2.9. The intraobserver CV was
      about 20%. CONCLUSIONS: This study strongly supports the need for standardisation
      among different centres when using skin scoring for clinical trials. The
      intraobserver variability and within-patient SD values can be significantly
      reduced by repeated teaching. For inexperienced rheumatologists, at least one
      repeated teaching course is needed.

PMID- 17234650
TI  - Calprotectin (a major leucocyte protein) is strongly and independently correlated
      with joint inflammation and damage in rheumatoid arthritis.
AB  - OBJECTIVE: Calprotectin is a major leucocyte protein, shown to correlate well
      with laboratory and clinical assessments in several inflammatory rheumatic
      diseases, and large concentrations of calprotectin have been found in synovial
      fluid from patients with rheumatoid arthritis (RA). The objective of the present
      study was to examine correlations between calprotectin and joint damage. METHODS:
      145 patients with RA were analysed cross sectionally with laboratory
      (calprotectin, C reactive protein (CRP), and erythrocyte sedimentation rate
      (ESR)), clinical (28 joint counts (tender, swollen), physician global VAS, DAS28
      and RA Articular Damage score (RAAD)), and radiographic (plain hand radiographs;
      modified Sharp's method) measurements, on the same day. RESULTS: Calprotectin
      showed a highly significant correlation with measures of joint damage; modified
      Sharp score r = 0.43 (p<0.001) and RAAD r = 0.40 (p<0.001). The association with
      modified Sharp score and RAAD score was maintained after adjustment for CRP, ESR,
      rheumatoid factor, DAS28, sex, and age in a multiple regression analysis (p =
      0.018 and p = 0.04, respectively), while neither CRP nor ESR showed any
      independent associations. Highly significant correlations (p<0.001) were also
      found between calprotectin and both laboratory and clinical markers of
      inflammation. CONCLUSION: Calprotectin was found to significantly and
      independently explain the variation in the radiological and clinical assessments
      of joint damage. Longitudinal studies are required to examine whether
      calprotectin may predict the progression of joint damage in RA.

PMID- 17234651
TI  - The TNFRSF1A R92Q mutation is frequent in rheumatoid arthritis but shows no
      evidence for association or linkage with the disease.
AB  - OBJECTIVE: TNFRSF1A mutations cause TNFRSF1A-associated periodic syndrome
      (MIM#142680). A recent study suggested that the R92Q mutation was associated with
      polyarthritis. We aimed to search for this and other TNFRSF1A mutations in
      rheumatoid arthritis (RA), and to test for linkage. METHODS: The DNA of 100 trio
      families and 86 index cases of RA-affected sib-pair (ASP) families from the
      French Caucasian population were investigated by denatured high-performance
      liquid chromatography for TNFRSF1A mutations in exons 2 to 4. The test for
      association compared cases and controls (derived from un-transmitted parental
      chromosomes). The test for linkage relied on the transmission disequilibrium test
      (TDT) in trio families and cosegregation in ASP families. RESULTS: Only the R92Q
      mutation was detected--in 2 of the 100 index cases of trio families and in 5
      (5.8%) of the index cases of ASP families, but also in 5% of the controls,
      showing no association with the disease. No RA linkage evidence was found in TDT
      and ASP RA families. CONCLUSION: This TNFRSF1A investigation in RA from the
      French Caucasian population showed only the R92Q mutation, with a frequency of
      4.5%, but no evidence for RA association or linkage to the disease. The R92Q
      mutation could be considered to be a low-penetrance variant.

PMID- 17234652
TI  - Clinical risk assessment of organ manifestations in systemic sclerosis: a report
      from the EULAR Scleroderma Trials And Research group database.
AB  - BACKGROUND: Systemic sclerosis (SSc) is a multisystem autoimmune disease, which
      is classified into a diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc)
      subset according to the skin involvement. In order to better understand the
      vascular, immunological and fibrotic processes of SSc and to guide its treatment,
      the EULAR Scleroderma Trials And Research (EUSTAR) group was formed in June 2004.
      AIMS AND METHODS: EUSTAR collects prospectively the Minimal Essential Data Set
      (MEDS) on all sequential patients fulfilling the American College of Rheumatology
      diagnostic criteria in participating centres. We aimed to characterise
      demographic, clinical and laboratory characteristics of disease presentation in
      SSc and analysed EUSTAR baseline visits. RESULTS: In April 2006, a total of 3656
      patients (1349 with dcSSc and 2101 with lcSSc) were enrolled in 102 centres and
      30 countries. 1330 individuals had autoantibodies against Scl70 and 1106 against
      anticentromere antibodies. 87% of patients were women. On multivariate analysis,
      scleroderma subsets (dcSSc vs lcSSc), antibody status and age at onset of
      Raynaud's phenomenon, but not gender, were found to be independently associated
      with the prevalence of organ manifestations. Autoantibody status in this analysis
      was more closely associated with clinical manifestations than were SSc subsets.
      CONCLUSION: dcSSc and lcSSc subsets are associated with particular organ
      manifestations, but in this analysis the clinical distinction seemed to be
      superseded by an antibody-based classification in predicting some scleroderma
      complications. The EUSTAR MEDS database facilitates the analysis of clinical
      patterns in SSc, and contributes to the standardised assessment and monitoring of
      SSc internationally.

PMID- 17234653
TI  - Umbilical cord milking reduces the need for red cell transfusions and improves
      neonatal adaptation in infants born at less than 29 weeks' gestation: a
      randomised controlled trial.
AB  - OBJECTIVE: To investigate the effects of umbilical cord milking on the need for
      red blood cell (RBC) transfusion and morbidity in very preterm infants. PATIENTS
      AND METHODS: 40 singleton infants born between 24 and 28 weeks' gestation were
      randomly assigned to receive umbilical cord clamped either immediately (control
      group, n = 20) or after umbilical cord milking (milked group, n = 20). Primary
      outcome measures were the probability of not needing transfusion, determined by
      Kaplan-Meier analysis, and the total number of RBC transfusions. Secondary
      outcome variables were haemoglobin value and blood pressure at admission.
      RESULTS: There were no significant differences in gestational age and birth
      weight between the two groups. The milked group was more likely not to have
      needed red cell transfusion (p = 0.02) and had a decreased number (mean (SD)) of
      RBC transfusions (milked group 1.7 (3.0) vs controls 4.0 (4.2); p = 0.02). The
      initial mean (SD) haemoglobin value was higher in the milked group (165 (14) g/l)
      than in the controls (141 (16) g/l); p<0.01). Mean (SD) blood pressure at
      admission was significantly higher in the milked group (34 (9) mm Hg) than in the
      controls 28 (8) mm Hg; p = 0.03). There was no significant difference in
      mortality between the groups. The milked group had a shorter duration of
      ventilation or supplemental oxygen than the control group. CONCLUSION: Milking
      the umbilical cord is a safe procedure, reducing the need for RBC transfusions,
      and the need for circulatory and respiratory support in very preterm infants.

PMID- 17234654
TI  - Surgery for hepatic neuroendocrine tumors: a single institutional experience in
      Japan.
AB  - BACKGROUND: Surgical resection has been advocated as an effective treatment for
      hepatic neuroendocrine tumors (HNETs) in Western countries, but few data are
      available to define its indications. We evaluated the results of Japanese
      patients to determine the prognostic factors and the feasibility of our
      aggressive surgical approach. METHODS: The records of all consecutive patients
      who underwent surgical resection for HNETs at our institution were
      retrospectively reviewed. Patients were selected for surgery if all tumors were
      deemed resectable, regardless of their extent. RESULTS: A total of 21 patients
      were identified. Bilobar disease was present in 13 patients (62%). Eleven
      patients (52%) underwent major hepatectomy, which included right
      trisectionectomy, extended right or left hepatectomy and right hepatectomy. No in
      hospital death occurred. The overall 1-, 3- and 5-year survival rates were 95, 68
      and 41%, respectively, with a median follow-up of 34 months. Metastatic HNETs
      from bronchopulmonary primaries exhibited significantly poor outcome compared
      with other primary sites (P = 0.04). Patients who underwent curative resection
      had an improved overall 5-year survival rate of 73% compared with palliative
      resection (0%, P = 0.01). The longest survival in the latter group was 57 months.
      Complete symptom resolution rate was 92%. CONCLUSIONS: This is the first study
      from Asia demonstrating the safety of aggressive hepatic resection for HNETs.
      Significant symptom relief and long-term survival were achieved irrespective of
      the extent of disease or the magnitude of operation. Metastatic HNETs from
      bronchopulmonary primaries may represent a more lethal subset of tumors.

PMID- 17234655
TI  - Congenital candidiasis presenting as septic shock without rash.
AB  - Congenital candidiasis is rare and often benign. We report the case of twins born
      at 32 weeks' gestation with different manifestations of congenital candidiasis.
      One twin was born well though neutropenic, and died from overwhelming sepsis with
      septic shock at 22 h. The other twin presented with a delayed onset of rash at 2
      days, remained well and survived.

PMID- 17234656
TI  - Prevalence of cardiovascular disease risk in Ontario adolescents.
AB  - We assessed traditional cardiovascular disease (CVD) risk factors in 3293
      Canadian adolescents (age: 14.1 (SD 0.6) years; body mass index (BMI): 23.0 (SD
      6.3)). Prevalence for obesity, borderline hypertension and hyperlipaemia was
      23.7% (95% CI 1.5%), 9.1% (95% CI 1.0%) and 9.7% (95% CI 1.0%), respectively,
      with increased estimates in children with low cardiorespiratory fitness (p<0.05).
      Participants demonstrated increased CVD risk, highlighting the necessity of
      placing adolescents in the forefront of preventive CVD programs.

PMID- 17234657
TI  - Randomised, double blind, placebo-controlled trial of selenium supplementation in
      adult asthma.
AB  - BACKGROUND: Epidemiological evidence from observational studies has suggested
      that blood levels and dietary intake of selenium of adults with asthma are lower
      than those of controls. The only previous trial of selenium supplementation in
      adults with asthma found no objective evidence of benefit but involved only 24
      participants. METHODS: A randomised, double blind, placebo-controlled trial of
      selenium supplementation was performed in adults with asthma in London, UK, the
      majority of whom (75%) reported inhaled steroid use at baseline. 197 participants
      were randomised to receive either a high-selenium yeast preparation (100 microg
      daily, n=99) or placebo (yeast only, n=98) for 24 weeks. The primary outcome was
      asthma-related quality of life (QoL) score. Secondary outcomes included lung
      function, asthma symptom scores, peak flow and bronchodilator usage. Linear
      regression was used to analyse the change in outcome between the two treatment
      arms by "intention to treat". RESULTS: There was a 48% increase in plasma
      selenium between baseline and end of trial in the active treatment group but no
      change in the placebo group. While the QoL score improved more in the active
      treatment group than in the placebo group, the difference in change in score
      between the two groups was not significant (-0.05 (95% CI -0.19 to 0.09);
      p=0.47). Selenium supplementation was not associated with any significant
      improvement in secondary outcomes compared with placebo. CONCLUSIONS: Selenium
      supplementation had no clinical benefit in adults with asthma, the majority of
      whom were taking inhaled steroids.

PMID- 17234659
TI  - Bronchial mucosal inflammation and upregulation of CXC chemoattractants and
      receptors in severe exacerbations of asthma.
AB  - BACKGROUND: A study was undertaken to test the hypothesis that severe
      exacerbations of asthma are characterised by increased bronchial mucosal
      neutrophilia associated with upregulation of neutrophil chemoattractant ligands
      and their specific cell surface receptors. METHODS: Immunohistology and in situ
      hybridisation were applied to endobronchial biopsy specimens from three groups:
      (1) 15 patients admitted to hospital with a severe exacerbation of asthma (E
      asthma), (2) 15 with stable asthma (S-asthma) and (3) 15 non-atopic and non
      smoker surgical controls (NSC). RESULTS: There were significantly more
      neutrophils and eosinophils in the epithelium and subepithelium of patients in
      the E-asthma group (median (range) neutrophils 7 (0-380) and 78 (10-898)/mm2,
      eosinophils 31 (0-167) and 60 (6-351)/mm2, p<or=0.01 compared with NSC: 0 (0-10,
      0-7, 0-18 and 0-3)/mm2, respectively), resulting in similar final densities of
      eosinophils and neutrophils. With respect to neutrophil chemoattractants and
      receptors, counts of CXCL5, CXCL8, CXCR1 and CXCR2 mRNA-positive cells in the
      subepithelium of the E-asthma group were, respectively, 5, 4, 4 and 18 times
      greater (p<or=0.01) than those of the NSC group. In the E-asthma group, cells
      expressing CXCL5 or CXCR2 were eightfold and threefold more frequent than those
      expressing CXCL8 or CXCR1 mRNA, respectively (p<0.01). CXCL5 and CXCR2 in E
      asthma were associated with the number of eosinophils (r=0.59 and 0.66, p<0.02
      for both) rather than the number of neutrophils. CONCLUSION: In severe
      exacerbations of asthma there is a bronchial mucosal neutrophilia, eosinophilia
      and upregulation of CXC chemoattractants and their receptors. CXCL5 and CXCR2
      have an association with eosinophila only, and these represent potentially new
      targets for treatment in exacerbations of asthma.

PMID- 17234658
TI  - Role of the renin-angiotensin system in ventilator-induced lung injury: an in
      vivo study in a rat model.
AB  - BACKGROUND: Injurious mechanical ventilation can cause a pro-inflammatory
      reaction in the lungs. Recent evidence suggests an association of the renin
      angiotensin system (RAS) with lung inflammation. A study was undertaken to
      investigate the pathogenic role of the RAS in ventilator-induced lung injury
      (VILI) and to determine whether VILI can be attenuated by angiotensin converting
      enzyme (ACE) inhibition. METHODS: Male Sprague-Dawley rats were mechanically
      ventilated for 4 h with low (7 ml/kg) or high (40 ml/kg) tidal volumes; non
      ventilated rats were used as controls. Lung injury and inflammation were measured
      by the lung injury score, protein leakage, myeloperoxidase activity, pro
      inflammatory cytokine levels and nuclear factor (NF)-kappaB activity. Expression
      of the RAS components was also assessed. Some rats were pretreated with the ACE
      inhibitor captopril (10 mg/kg) for 3 days or received a concomitant infusion with
      losartan or PD123319 (type 1 or type 2 angiotensin II receptor antagonist) during
      mechanical ventilation to assess possible protective effects on VILI. RESULTS: In
      the high-volume group (n=6) the lung injury score, bronchoalveolar lavage fluid
      protein concentration, pro-inflammatory cytokines and NF-kappaB activities were
      significantly increased compared with controls (n=6). Lung tissue angiotensin II
      levels and mRNA levels of angiotensinogen and type 1 and type 2 angiotensin II
      receptors were also significantly increased in the high-volume group.
      Pretreatment with captopril or concomitant infusion with losartan or PD123319 in
      the high-volume group attenuated the lung injury and inflammation (n=6 for each
      group). CONCLUSIONS: The RAS is involved in the pathogenesis of ventilator
      induced lung injury. ACE inhibitor or angiotensin receptor antagonists can
      attenuate VILI in this rat model.

PMID- 17234660
TI  - Nitrogen dioxide induces apoptosis and proliferation but not emphysema in rat
      lungs.
AB  - BACKGROUND: Apoptosis of alveolar septal cells has been linked to emphysema
      formation. Nitrogen dioxide, a component of cigarette smoke, has been shown to
      induce alveolar epithelial cell apoptosis in vitro. It is hypothesised that
      exposure of rats to nitrogen dioxide may result in increased alveolar septal cell
      apoptosis in vivo with ensuing emphysema-that is, airspace enlargement and loss
      of alveolar walls. METHODS: Fischer 344 rats were exposed to 10 ppm nitrogen
      dioxide for 3, 7, 21 days or 21 days followed by 28 days at room air. Age-matched
      control rats were exposed to room air for 3, 21 or 49 days. Lungs fixed at 20 cm
      fluid column, embedded in paraffin wax, glycol methacrylate and araldite, were
      analysed by design-based stereology. Alveolar septal cell apoptosis (transferase
      dUTP nick end labelling assay, active caspase 3) and proliferation (Ki-67),
      airspace enlargement, total alveolar surface area, and absolute alveolar septal
      volume as well as the ultrastructural composition of the alveolar wall were
      quantified. RESULTS: Nitrogen dioxide resulted in an eightfold increase in
      alveolar septal cell apoptosis at day 3 and a 14-fold increase in proliferation
      compared with age-matched controls. Airspace enlargement, indicated by a 20%
      increase in mean airspace chord length, was evident by day 7 but was not
      associated with loss of alveolar walls. By contrast, nitrogen dioxide resulted in
      an increase in the total surface area and absolute volume of alveolar walls
      comprising all compartments. The ratio of collagen to elastin, however, was
      reduced at day 21. Lungs exposed to nitrogen dioxide for 21 days exhibited
      quantitative structural characteristics as seen in control lungs on day 49.
      CONCLUSIONS: Nitrogen dioxide exposure of rats results in increased alveolar
      septal cell turnover leading to accelerated lung growth, which is associated with
      an imbalance in the relative composition of the extracellular matrix, but fails
      to induce emphysema.

PMID- 17234662
TI  - A matter of necessity? Enforced treatment under the Mental Health Act. R. (JB) v.
      Responsible Medical Officer Dr A Haddock, Mental Health Act Commission second
      opinion appointed doctor Dr Rigby, Mental Health Act Commission second opinion
      appointed Doctor Wood.

PMID- 17234661
TI  - Survey of acute renal failure in patients with cystic fibrosis in the UK.
AB  - BACKGROUND: There has been a recent increase in the number of reported cases of
      acute renal failure (ARF) in cystic fibrosis (CF). A study was undertaken to
      determine the incidence risk of ARF in patients with CF in the UK and to identify
      possible aetiological factors. METHODS: All doctors working at UK CF centres were
      asked if they had been involved with the management of a patient with CF who had
      developed ARF. Those responding positively were asked to request informed consent
      for entry into the study and the patient's case notes were then reviewed. The
      analysis was restricted to patients developing ARF between 1997 and 2004. A
      second questionnaire sought information on aminoglycoside prescribing practice.
      RESULTS: Responses were received from 55 of 56 centres with 64 reports, 9 of
      which were duplicates, leaving 55 cases. Consent was obtained for data extraction
      in 26 cases, of which 24 fitted the criteria for ARF (verified data). Median age
      at presentation with ARF was 9.7 years (range 0.4-31.8) and 12 cases were male.
      The incidence risk of ARF was 4.6 (verified data) to 10.5 cases (all data)/10,000
      CF patients/year. In 21 cases (88%) an aminoglycoside was prescribed at onset of
      ARF or in the preceding week; 16 (76%) of those receiving an aminoglycoside had
      gentamicin. A renal biopsy was performed in 7 cases and histological examination
      revealed acute tubular necrosis in 6, all of whom had received gentamicin. Renal
      dialysis was required in 13 cases (54%). Complete recovery was seen in 22/24
      patients (92%). CONCLUSIONS: ARF is increasingly being recognised in patients
      with CF. There is significant morbidity with most patients requiring dialysis.
      This study implicates intravenous aminoglycosides, particularly gentamicin, in
      the aetiology of ARF in CF.

PMID- 17234663
TI  - Nodular pulmonary amyloidosis and Sjogren's syndrome in a patient treated with
      intermittent haemodialysis (IHD).

PMID- 17234664
TI  - Adiponectin--an adipokine with unique metabolic properties.

PMID- 17234665
TI  - Renal artery aneurysm in a cadaveric kidney transplantation.

PMID- 17234666
TI  - A novel renal perspective of preeclampsia: a look from the podocyte.

PMID- 17234667
TI  - Thyroiditis and iodide mumps following an angioplasty.

PMID- 17234668
TI  - Azathioprine, UV light, and skin cancer in organ transplant patients--do we have
      an answer?

PMID- 17234670
TI  - Understanding recent haemoglobin trials in CKD: methods and lesson learned from
      CREATE and CHOIR.

PMID- 17234669
TI  - Binding of highly concentrated maxacalcitol to the nuclear vitamin D receptors of
      parathyroid cells.
AB  - BACKGROUND: Injection of maxacalcitol (OCT) directly into the parathyroid gland
      (PTG) is a clinically safe and effective treatment for advanced secondary
      hyperparathyroidism (A-SHPT) resistant to conventional medical treatment. In the
      present study, the degree of nuclear localization of directly injected OCT in
      parathyroid cells (PTC) was investigated by microautoradiography (mARG) in a
      model of A-SHPT. METHODS: The 5/6 nephrectomized Sprague-Dawley rats were fed a
      high-phosphate and low-calcium diet for 8 weeks and consequently the level of
      vitamin D receptor (VDR) in their PTC severely decreased. The bilateral PTG were
      surgically exposed and only the left gland were directly injected with 3H-OCT (DI
      3H-OCT). The time course of the changes in both radioactivity and localization of
      3H-OCT in the bilateral glands was analysed using a bioimaging analyser system
      and mARG, respectively. A very high dose of unlabelled calcitriol was
      administered intravenously (IV-1,25D3) prior to DI-3H-OCT, as a competitive
      study. RESULTS: Peak radioactivity levels in the directly injected and intact PTG
      occured immediately and 1 h, respectively, after DI-3H-OCT, and the difference
      was about 50-fold higher in the treated gland. The of mARG showed a marked
      concentration of silver grains in the nuclei of PTC in the gland treated with DI
      3H-OCT and that concentration was significantly suppressed by IV-1,25D3.
      CONCLUSIONS: Direct injection of OCT into the PTG enables the administration of
      the highly concentrated drug for specific binding to nuclear vitamin D binding
      sites, including VDR of PTC, which markedly suppresses the parathyroid hormone,
      improves the response to calcium and vitamin D and induces apoptosis in PTC.

PMID- 17234671
TI  - Professor Fokko J. van der Woude.

PMID- 17234672
TI  - Glycosyl hydrolases of cell wall are induced by sugar starvation in Arabidopsis.
AB  - Three Arabidopsis genes encoding a putative beta-galactosidase (At5g56870), beta
      xylosidase (At5g49360) and beta-glucosidase (At3g60140) are induced by sugar
      starvation. The deduced proteins belong to the glycosyl hydrolase families 35, 3
      and 1, respectively. They are predicted to be secretory proteins that play roles
      in modification of cell wall polysaccharides based on amino acid similarity. The
      beta-galactosidase encoded by At5g56870 was identified as a secretory protein in
      culture medium of suspension cells by mass spectrometry analysis. This protein
      was specifically detected under sugar-starved conditions with a specific
      antibody. Induction of these genes was repressed in suspension cells grown with
      galactose, xylose and glucose, as well as with sucrose. In planta, expression of
      the genes and protein accumulation were detected when photosynthesis was
      inhibited. Glycosyl hydrolase activity against galactan also increased during
      sugar starvation. The amount of monosaccharide in pectin and hemicellulose in
      detached leaves decreased in response to sugar starvation. These findings suggest
      that the cell wall may function as a storage reserve of carbon in addition to
      providing physical support for the plant body.

PMID- 17234673
TI  - Maximum number of live births per donor in artificial insemination.
AB  - BACKGROUND: The maximal number of live births (k) per donor was usually
      determined by cultural and social perspective. It was rarely decided on the basis
      of scientific evidence or discussed from mathematical or probabilistic viewpoint.
      METHODS AND RESULTS: To recommend a value for k, we propose three criteria to
      evaluate its impact on consanguinity and disease incidence due to artificial
      insemination by donor (AID). The first approach considers the optimization of k
      under the criterion of fixed tolerable number of consanguineous mating due to
      AID. The second approach optimizes k under fixed allowable average coefficient of
      inbreeding. This approach is particularly helpful when assessing the impact on
      the public, is of interest. The third criterion considers specific inheritance
      diseases. This approach is useful when evaluating the individual's risk of
      genetic diseases. When different diseases are considered, this criterion can be
      easily adopted. All these derivations are based on the assumption of shortage of
      gamete donors due to great demand and insufficient supply. CONCLUSIONS: Our
      results indicate that strong degree of assortative mating, small population size
      and insufficient supply in gamete donors will lead to greater risk of
      consanguinity. Recommendations under other settings are also tabulated for
      reference. A web site for calculating the limit for live births per donor is
      available.

PMID- 17234674
TI  - The predictive value of medical history taking and Chlamydia IgG ELISA antibody
      testing (CAT) in the selection of subfertile women for diagnostic laparoscopy: a
      clinical prediction model approach.
AB  - BACKGROUND: Medical history taking as well as Chlamydia antibody titre (CAT)
      testing are currently used in the selection of patients for diagnostic
      laparoscopy with tubal patency testing. Most research has focused on the
      predictive value of CAT in isolation from medical history. We assessed therefore
      whether the combination of medical history and CAT improves the efficiency of
      selecting patients for laparoscopy as compared to the use of either medical
      history or CAT. METHODS: Data of 207 consecutive subfertile women were used to
      create multivariable logistic regression models for the prediction of tubal
      disease as diagnosed by diagnostic laparoscopy. RESULTS: The model with data of
      medical history only had an area under the receiver operating characteristic
      curve (AUC) of 0.65 (95% CI 0.56-0.74). Addition of CAT increased the AUC to 0.70
      (95% CI 0.62-0.78) (P = 0.065). CAT was positive in 40 women and showed a
      sensitivity of 0.37 (95% CI 0.26-0.49) for a specificity of 0.88 (95% CI 0.82
      0.93). In CAT positive women, a blank medical history did not decrease the
      probability of tubal disease. Of the 167 women tested CAT negative, 23 (14%)
      still had a high probability of disease due to their medical history and 11 of
      them (48%) showed tubal abnormalities on diagnostic laparoscopy. CONCLUSIONS: CAT
      testing adds valuable information to a woman's risk profile based on her medical
      history. The combination of medical history taking and CAT testing has a better
      yield for diagnosing tubal disease than either of these alone.

PMID- 17234675
TI  - Lidocaine-prilocaine (EMLA) cream as analgesia for hysterosalpingography: a
      prospective, randomized, controlled, double blinded study.
AB  - BACKGROUND: The aim of our study is to evaluate the efficacy of applying
      lidocaine 25 mg-prilocaine-25 mg/G cream (EMLA 5%) on the uterine cervix for pain
      relief when performing hysterosalpingography (HSG). METHODS: Eighty-two patients
      undergoing HSG as part of infertility evaluation were randomized into groups
      receiving EMLA (42) or placebo cream (40) in a double-blinded prospective study
      from which four women were later excluded. The cream was applied to the uterine
      cervix by means of a cervical cup 30 min before the HSG. Pain perception related
      to the HSG procedure was scored by visual analogue scale (VAS) at five predefined
      steps: after speculum application, after cervical instrumentation of the
      tenaculum and cannula, at the end of uterine filling, at completion of tubal
      spillage, and immediately following instrument removal. In addition, the patients
      were asked to retrospectively rate the pain during the entire procedure in a
      telephone interview the following day. RESULTS: Cervical instrumentation was
      found to be the most painful step of HSG (P < 0.001). When comparing the VAS pain
      scores, cervical instrumentation in the EMLA-treated patients was associated with
      significantly less pain than the control group: 3.3 +/- 2.9 versus 4.9 +/- 2.7,
      respectively (P = 0.02). CONCLUSIONS: Topical application of EMLA 5% cream on the
      uterine cervix before performing HSG significantly reduced the pain during this
      procedure.

PMID- 17234676
TI  - Endometriosis: an inflammatory disease with a Th2 immune response component.
AB  - BACKGROUND: Efforts have been made to correctly characterize the role of the
      immune response in endometriosis. The objective of this study was to analyse the
      interaction between Th1 and Th2 immune response patterns and endometriosis by
      evaluating a panel of cytokines. METHODS: Between January 2004 and November 2005,
      98 patients, classified into two groups according to the histologically confirmed
      presence (Group A) or absence of endometriosis (Group B), were evaluated.
      Interleukins (IL) 2, 4 and 10, tumour necrosis factor-alpha and interferon-gamma
      (IFN-gamma) were measured by flow cytometry in the peripheral blood and
      peritoneal fluid of all patients. RESULTS: IFN-gamma and IL-10 levels were
      significantly higher in the peritoneal fluid of patients with endometriosis
      compared to those without endometriosis (P < 0.05). There was a significant
      alteration in the IL-4/IFN-gamma (P < 0.001), IL-4/IL-2 (P = 0.006), IL-10/IFN
      gamma (P < 0.001) and the IL-10/IL-2 ratios (P < 0.001) in the peritoneal fluid
      of patients with endometriosis, with a predominance of IL-4 and IL-10, reflecting
      a shift towards Th2 immune response despite the increase in IFN-gamma
      concentrations. CONCLUSIONS: Endometriosis is an inflammatory disease involving a
      possible shift towards Th2 immune response component, as demonstrated by the
      relative increase in cytokines characteristic of this pattern of immune response.

PMID- 17234677
TI  - High-dose atorvastatin causes regression of endometriotic implants: a rat model.
AB  - BACKGROUND: This prospective randomized-controlled animal study was designed to
      determine the effects of atorvastatin on experimentally induced endometriosis in
      a rat model. METHODS: Thirty-seven Wistar-Albino rats in which endometriotic
      implants were induced were randomly divided into four groups. Group I (Low-dose
      atorvastatin group, eight rats) were given 0.5 mg kg(-1) day(-1) oral
      atorvastatin. Group II (High-dose atorvastatin group, 10 rats) were given 2.5 mg
      kg(-1) day(-1) oral atorvastatin. Group III were given a single dose of 1 mg kg(
      1) s.c. leuprolide acetate (GnRH agonist group, nine rats). Group IV were given
      no medication and served as controls (10 rats). All rats received the treatment
      for 21 days and were then euthanized to assess the implants' size, vascular
      endothelial growth factor (VEGF) level in peritoneal fluid and histological
      score. RESULTS: At the end of the treatment, the mean areas of implants were
      smaller and VEGF levels in peritoneal fluid were lower in Groups II and III than
      those in Group I and the control group (all P < 0.05). The mean areas of implants
      decreased from 41.2 +/- 13.9 to 22.7 +/- 13.9 mm(2) after medication in Group II
      and decreased from 41.2 +/- 18.1 to 13.1 +/- 13.8 mm(2) in Group III (both P <
      0.05), whereas in Group I, the mean area increased from 43.0 +/- 12.7 to 50.5 +/-
      13.9 mm(2) (P < 0.05). CONCLUSIONS: High-dose atorvastatin caused a significant
      regression of endometriotic implants.

PMID- 17234678
TI  - Prognostic capacity of transvaginal hydrolaparoscopy to predict spontaneous
      pregnancy.
AB  - BACKGROUND: In 1998, transvaginal hydrolaparoscopy (THL) was introduced as a new
      outpatient procedure for exploration of tubo-ovarian structures and tubal patency
      in subfertile patients. At present, there are no large studies that relate the
      findings at THL to fertility outcome. METHODS: Consecutive patients undergoing
      THL for subfertility between 2000 and 2004 were included in this prospective
      cohort study. Follow-up ended when ongoing pregnancy or tubal surgery occurred or
      at the day of last contact. Kaplan-Meier curves for the occurrence of
      intrauterine pregnancy (IUP) (spontaneous or after intrauterine insemination)
      were constructed for a normal THL, a THL with a one-sided tubal pathology and a
      THL with a two-sided tubal pathology. Fecundity rate ratios (FRRs) were
      calculated to express the association between THL findings and the occurrence of
      IUP. Patients rated their pain experiences and acceptability on a visual analogue
      scale (VAS). RESULTS: We included 272 women. In 96% (261) of the patients, access
      to the pouch of Douglas was achieved. Complications occurred in 2% of the
      procedures. In 203 (78%) patients, both tubo-ovarian structures could be
      visualized and tubal patency was shown. One-sided tubal occlusion was found in
      10%, whereas two-sided tubal occlusion was seen in 4% of the patients. Adhesions
      and/or endometriosis were observed in 8% of the patients. The FRRs for one-sided
      tubal pathology, two-sided tubal pathology and adhesions/endometriosis were 0.59,
      0 and 0.80, respectively. The VAS scores showed pain to be limited and the
      procedure to be acceptable. CONCLUSION: THL is a feasible technique. Its capacity
      to predict spontaneous ongoing pregnancy is comparable to that of laparoscopy.

PMID- 17234679
TI  - An inducible system for expression and validation of the specificity of short
      hairpin RNA in mammalian cells.
AB  - RNA interference (RNAi) by means of short hairpin RNA (shRNA) has developed into
      a powerful tool for loss-of-function analysis in mammalian cells. The principal
      problem in RNAi experiments is off-target effects, and the most vigorous
      demonstration of the specificity of shRNA is the rescue of the RNAi effects with
      a shRNA-resistant target gene. This presents its own problems, including the
      unpredictable relative expression of shRNA and rescue cDNA in individual cells,
      and the difficulty in generating stable cell lines. In this report, we evaluated
      the plausibility of combining the expression of shRNA and rescue cDNA in the same
      vector. In addition to facilitate the validation of shRNA specificity, this
      system also considerably simplifies the generation of shRNA-expressing cell
      lines. Since the compensatory cDNA is under the control of an inducible promoter,
      stable shRNA-expressing cells can be generated before the knockdown phenotypes
      are studied by conditionally turning off the rescue protein. Conversely, the
      rescue protein can be activated after the endogenous protein is completely
      repressed. This approach is particularly suitable when prolonged expression of
      either the shRNA or the compensatory cDNA is detrimental to cell growth. This
      system allows a convenient one-step validation of shRNA and generation of stable
      shRNA-expressing cells.

PMID- 17234680
TI  - Stem cell factor-mediated activation pathways promote murine eosinophil CCL6
      production and survival.
AB  - Eosinophil activation during allergic diseases has a detrimental role in the
      generation of pathophysiologic responses. Stem cell factor (SCF) has recently
      shown an inflammatory, gene-activating role on eosinophils and contributes to the
      generation of pathophysiologic changes in the airways during allergic responses.
      The data in the present study outline the signal transduction events that are
      induced by SCF in eosinophils and further demonstrate that MEK-mediated signaling
      pathways are crucial for SCF-induced CCL6 chemokine activation and eosinophil
      survival. SCF-mediated eosinophil activation was demonstrated to include PI-3K
      activation as well as MEK/MAPK phosphorylation pathways. Subsequent analysis of
      CCL6 gene activation and production induced by SCF in the presence or absence of
      rather specific inhibitors for certain pathways demonstrated that the MEK/MAPK
      pathway but not the PI-3K pathway was crucial for the SCF-induced CCL6 gene
      activation. These same signaling pathways were shown to initiate antiapoptotic
      events and promote eosinophil survival, including up-regulation of BCL2 and BCL3.
      Altogether, SCF appears to be a potent eosinophil activation and survival factor.

PMID- 17234681
TI  - Interleukin-18 regulates pathological intraocular neovascularization.
AB  - Recently, the proinflammatory cytokine IL-18 has been shown to have a role in
      angiogenesis. This study aimed to elucidate its role in abnormal
      neovascularization (NV) in an oxygen-induced retinopathy (OIR) mouse model of the
      retinopathy seen in human premature newborns. IL-18 was constitutively expressed
      in the retina in C57BL/6 mice, but expression transiently dropped on Day 17 after
      birth in mice exposed to 75% oxygen for 5 days between Days 7 and 12. Coincident
      with the IL-18 reduction in oxygen-treated mice, vascular endothelial growth
      factor was expressed in the retina, and OIR developed. By Day 24, NV in the
      retina had regressed to normal levels. By contrast, IL-18 knockout mice, exposed
      to elevated oxygen concentrations, developed more severe OIR on Day 17, and it is
      important that this persisted until Day 24. This suggested that IL-18 negatively
      regulated retinal NV. To investigate this further, we administrated recombinant
      IL-18 to C57BL/6 mice during the development of OIR but found no significant
      inhibition of retinopathy. However, when IL-18-binding protein was administered
      during the OIR recovery phase to neutralize endogenous IL-18, OIR was still
      apparent on Day 24. We therefore concluded that IL-18 regulates pathogenic
      retinal NV by promoting its regression rather than inhibiting its development.
      This suggests some useful, new approaches to treating retinopathy in humans.

PMID- 17234682
TI  - Massive, sustained gammadelta T cell migration from the bovine skin in vivo.
AB  - In all species studied so far, gammadelta T cells are abundantly present in
      epithelia. The functions of these cells are largely unknown. Using a lymph duct
      cannulation method, which is only possible in large animals such as cattle, we
      show that large numbers of gammadelta T cells, but not alphabeta T cells, are
      constitutively present in pseudoafferent lymph draining bovine skin. The
      gammadelta T cells, which are present in pseudoafferent lymph, use Vgamma
      segments that are characteristic for bovine dermal gammadelta T cells, suggesting
      that these cells migrated from the skin. Further supporting the origin of these
      cells is the fact that fluorescent latex beads injected in the skin could be
      recovered in cells in the pseudoafferent lymph. The cannulation method is
      minimally invasive, and the lymph flow, which was sustained and remained
      essentially unaltered during 14 days, closely represents the in vivo situation.
      The gammadelta T cells could not be induced to produce IFN-gamma, TNF-alpha, and
      IL-10, and they did not express costimulatory molecules, IL-2 receptor, and MHC
      Class II molecules. The level of gammadelta T cell egress was 6.7x10(3)
      gammadelta T cells per cm2 skin per hour, which is enough to deplete all
      gammadelta T cells from the skin within 46 h. As this massive gammadelta T cell
      migration was observed during 14 days, constant replenishment of these cells must
      take place. Our data suggest that gammadelta T cells in tissues fulfill more than
      exclusively local functions.

PMID- 17234683
TI  - Tailoring a novel sialic acid-binding lectin from a ricin-B chain-like galactose
      binding protein by natural evolution-mimicry.
AB  - Sialic acid (Sia) is a typical terminal sugar, which modifies various types of
      glycoconjugates commonly found in higher animals. Its regulatory roles in diverse
      biological phenomena are frequently triggered by interaction with Sia-binding
      lectins. When using natural Sia-binding lectins as probes, however, there have
      been practical problems concerning their repertoire and availability. Here, we
      show a rational creation of a Sia-binding lectin based on the strategy 'natural
      evolution-mimicry', where Sia-binding lectins are engineered by error-prone PCR
      from a Gal-binding lectin used as a scaffold protein. After selection with fetuin
      agarose using a recently reinforced ribosome display system, one of the evolved
      mutants SRC showed substantial affinity for alpha2-6Sia, which the parental Gal
      binding lectin EW29Ch lacked. SRC was found to have additional practical
      advantages in productivity and in preservation of affinity for Gal. Thus, the
      developed novel Sia-recognition protein will contribute as useful tools to
      sialoglycomics.

PMID- 17234684
TI  - Inhibition of reversed electron transfer and proton transport in the beef heart
      cytochrome bc1 complex by chemical modification.
AB  - Chemical modification of the bovine heart cytochrome bc1 complex with N
      (ethoxycarbonyl)-2-ethoxy-1,2-dihydroquinoline (EEDQ) has been reported to
      inhibit the proton pumping activity without affecting the rate of electron
      transfer to ferricytochrome c. This study aims to examine the effect of EEDQ on
      energy-linked reversed electron transfer in the bc1 complex reconstituted into
      potassium-loaded phospholipid vesicles. Generation of a valinomycin-mediated
      potassium-diffusion potential induced the reduction of cytochrome b in the
      reconstituted bc1 complex in the presence of sodium ascorbate. The time course of
      the cytochrome b reduction was well correlated with that of the absorbance change
      of safranine, an optical probe for measuring membrane potential. Treatment of the
      bc1 complex with EEDQ caused a decrease in the potential-induced reduction of
      cytochrome b as well as in the proton translocation activity. But a significant
      loss in the ubiquinol-cytochrome c reducing activity was not observed in the EEDQ
      treated bc1 complex. The time- and concentration-dependent effect of EEDQ on the
      reversed electron transfer was well correlated with that of the proton
      translocation activity of the bc1 complex. These findings strongly support the
      idea that the potential-induced reversal of electron transfer is coupled to the
      reverse flow of protons in the cytochrome bc1 complex.

PMID- 17234685
TI  - Functional and structural characterization of D-aspartate oxidase from porcine
      kidney: non-Michaelis kinetics due to substrate activation.
AB  - D-aspartate oxidase (DDO, EC 1.4.3.1) catalyzes dehydrogenation of D-aspartate to
      iminoaspartate and the subsequent re-oxidation of reduced FAD with O2 to produce
      hydrogen peroxide. In the mammalian neuroendocrine system, D-aspartate, a natural
      substrate, plays important roles in the regulation of the synthesis and secretion
      of hormones. To elucidate the kinetic and structural properties of native DDO, we
      purified DDO from porcine kidney to homogeneity, cloned the cDNA, and
      overexpressed the enzyme in Escherichia coli. The purified DDO was a homotetramer
      with tightly-bound FAD. The enzyme consisted of 341 amino acids and had GAGVMG as
      the dinucleotide binding motif and a C-terminal SKL peroxisomal-targeting signal
      sequence. Porcine DDO showed a strong affinity for meso-tartrate (Kd = 118
      microM). The oxidase exhibited pronounced substrate activation at D-aspartate and
      D-glutamate concentrations, [S], higher than 0.2 and 4 mM, respectively, and the
      [S]/v versus [S] plot showed marked downward curvature (v, the initial velocity),
      whereas substrate inhibition occurred with N-methyl-D-aspartate. These kinetic
      properties of DDO suggested that at high substrate concentrations, the FAD
      reduced form of the enzyme also catalyzes the reaction: the oxidative half
      reaction precedes the reductive one. The present direct approach to the analysis
      of non-Michaelis kinetics is indispensable for understanding the functional
      properties of DDO.

PMID- 17234686
TI  - Pim kinase substrate identification and specificity.
AB  - The Pim family of Ser/Thr kinases has been implicated in the process of
      lymphomagenesis and cell survival. Known substrates of Pim kinases are few and
      poorly characterized. In this study we set out to identify novel Pim-2 substrates
      using the Kinase Substrate Tracking and Elucidation (KESTREL) approach. Two
      potential substrates, eukaryotic initiation factor 4B (eIF4B) and apoptosis
      inhibitor 5 (API-5), were identified from rat thymus extracts. Sequence
      comparison of the Pim-2 kinase phosphorylation sites of eIF4B and mouse BAD, the
      only other known Pim-2 substrate, revealed conserved amino acids preceding the
      phosphorylated serine residue. Stepwise replacement of the conserved residues
      produced a consensus sequence for Pim kinase recognition: RXRHXS. Pim-1 and Pim-2
      catalyzed the phosphorylation of this recognition sequence 20-fold more
      efficiently than the original (K/R-K/R-R-K/R-L-S/T-a; a = small chain amino acid)
      Pim-1 phosphorylation site. The identification of the novel Pim kinase consensus
      sequence provides a more sensitive and versatile peptide based assay for
      screening modulators of Pim kinase activity.

PMID- 17234687
TI  - Oxidatively damaged DNA in aging dyslipidemic ApoE-/- and wild-type mice.
AB  - The free radical theory of aging depicts an accumulation of cellular oxidatively
      damaged DNA. In this study, we investigated this theory in mice with knocked-out
      apolipoprotein E gene (ApoE(-/-)), which develops atherosclerosis and wild-type
      counterparts. The level of oxidatively damaged DNA was investigated as strand
      breaks, endonuclease III- and formamidopyrimidine DNA glycosylase-sensitive sites
      by the comet assay. The level of DNA damage was mainly increased with age in the
      liver of ApoE(-/-) mice, whereas no increase was observed in the aorta or lung of
      the mice. This suggests that the accumulation of oxidized DNA in the liver of
      dyslipidemic ApoE(-/-) mice could be secondary to dysfunction of the lipid
      metabolism. Visually, the aortas of the ApoE(-/-) mice were clearly
      atherosclerotic as indicated by rigid texture and yellowish in color. However,
      the unaltered levels of oxidized DNA in severely atherosclerotic aortas of old (
      approximately 70 weeks) ApoE(-/-) mice indicate that oxidative stress may not be
      a generalized phenomenon, but rather related locally to the individual plaques.
      In conclusion, the results of this study suggest that dyslipidemic ApoE(-/-) mice
      suffer from hepatic oxidative stress in terms of oxidized DNA, and this effect
      could be due to the dysfunction of lipid metabolism.

PMID- 17234688
TI  - A circuit within a circuit?

PMID- 17234689
TI  - Volitional control of neural activity: implications for brain-computer
      interfaces.
AB  - Successful operation of brain-computer interfaces (BCI) and brain-machine
      interfaces (BMI) depends significantly on the degree to which neural activity can
      be volitionally controlled. This paper reviews evidence for such volitional
      control in a variety of neural signals, with particular emphasis on the activity
      of cortical neurons. Some evidence comes from conventional experiments that
      reveal volitional modulation in neural activity related to behaviours, including
      real and imagined movements, cognitive imagery and shifts of attention. More
      direct evidence comes from studies on operant conditioning of neural activity
      using biofeedback, and from BCI/BMI studies in which neural activity controls
      cursors or peripheral devices. Limits in the degree of accuracy of control in the
      latter studies can be attributed to several possible factors. Some of these
      factors, particularly limited practice time, can be addressed with long-term
      implanted BCIs. Preliminary observations with implanted circuits implementing
      recurrent BCIs are summarized.

PMID- 17234690
TI  - Signalling mechanisms in contraction-mediated stimulation of intracellular NO
      production in cat ventricular myocytes.
AB  - In this study we sought to determine whether contractile activity has a role as a
      signalling mechanism in the activation of intracellular nitric oxide (NO(i))
      production induced by electrical stimulation of cat ventricular myocytes. Field
      stimulation (FS) of single ventricular myocytes elicited frequency-dependent
      increases in NO(i) that were blocked by the calmodulin (CaM) inhibitor 10 microM
      W-7 and partially inhibited by the phosphatidylinositol 3'-kinase (PI-(3)K)
      inhibitor 10 microMm LY294002. Increasing extracellular [Ca(2+)] caused a
      concentration-dependent increase in FS-induced NO(i) that was partially inhibited
      by LY294002. The negative inotropic agents BDM (5 mm) or blebbistatin (10 microM)
      decreased cell shortening and NO(i) production without concomitant changes in L
      type Ca(2+) current (I(Ca,L)) or [Ca(2+)](i) transients. The positive inotropic
      agents EMD 57033 or CGP 48506 (1 microM) increased cell shortening and NO(i)
      production without concomitant changes in I(Ca,L) or [Ca(2+)](i) transients. FS
      induced NO(i) production was decreased in myocytes infected (100 multiplicity of
      viral infection (MOI); 24 h) with a replication-deficient adenovirus expressing a
      dominant-negative mutant of protein kinase B (Akt) compared with cells infected
      with a control adenovirus expressing beta-galactosidase. FS-induced NO(i) was
      partially inhibited by either endothelial (eNOS) or neuronal nitric oxide
      synthase (nNOS) inhibitors and completely blocked by simultaneous exposure to
      both. FS-induced [Ca(2+)](i) transients were increased by the nNOS inhibitor nNOS
      I (0.24 microM), decreased by the eNOS inhibitor L-NIO (1 microM) and unchanged
      by exposure to both inhibitors. We conclude that in cat ventricular myocytes, FS
      induced NO(i) production requires both Ca(2+)-dependent CaM signalling and Ca(2+)
      independent PI-(3)K-Akt signalling activated by contractile activity. FS
      activates NO(i) production from both eNOS and nNOS, and each source of NO(i)
      exerts opposing effects on [Ca(2+)](i) transient amplitude. These findings are
      important for understanding the regulation of NO(i) signalling in the normal and
      mechanically failing heart.

PMID- 17234691
TI  - Interactions between cardiac, respiratory and EEG-delta oscillations in rats
      during anaesthesia.
AB  - We hypothesized that, associated with the state of anaesthesia, characteristic
      changes exist in both cardio-respiratory and cerebral oscillator parameters and
      couplings, perhaps varying with depth of anaesthesia. Electrocardiograms (ECGs),
      respiration and electroencephalograms (EEGs) were recorded from two groups of 10
      rats during the entire course of anaesthesia following the administration of a
      single bolus of ketamine-xylazine (KX group) or pentobarbital (PB group). The
      phase dynamics approach was then used to extract the instantaneous frequencies of
      heart beat, respiration and slow delta-waves (within 0.5-3.5 Hz). The amplitudes
      of delta- and theta-waves were analysed by use of a time-frequency representation
      of the EEG signal within 0.5-7.5 Hz obtained by wavelet transformation, using the
      Morlet mother wavelet. For the KX group, where slow delta-waves constituted the
      dominant spectral component, the Hilbert transform was applied to obtain the
      instantaneous delta-frequency. The theta-activity was spread over too wide a
      spectral range for its phase to be meaningfully defined. For both agents, we
      observed two distinct phases of anaesthesia, with a marked increase in theta-wave
      activity occurring on passage from a deeper phase of anaesthesia to a shallower
      one. In other respects, the effects of the two anaesthetics were very different.
      For KX anaesthesia, the two phases were separated by a marked change in all three
      instantaneous frequencies: stable, deep, anaesthesia with small frequency
      variability was followed by a sharp transition to shallow anaesthesia with large
      frequency variability, lasting until the animal awoke. The transition occurred 16
      76 min after injection of the anaesthetic, with simultaneous reduction in the
      delta-wave amplitude. For PB anaesthesia, the two epochs were separated by the
      return of a positive response to the pinch test at 53-94 min, following which it
      took a further period of 45-70 min for the animal to awaken. delta-Waves were not
      apparent at any stage of PB anaesthesia. We applied non-linear dynamics and
      information theory to seek evidence of causal relationships between the cardiac,
      respiratory and slow delta-oscillations. We demonstrate that, for both groups,
      respiration drives the cardiac oscillator during deep anaesthesia. During shallow
      KX anaesthesia the direction either reverses, or the cardio-respiratory
      interaction becomes insignificant; in the deep phase, there is a unidirectional
      deterministic interaction of respiration with slow delta-oscillations. For PB
      anaesthesia, the cardio-respiratory interaction weakens during the second phase
      but, otherwise, there is no observable change in the interactions. We conclude
      that non-linear dynamics and information theory can be used to identify different
      stages of anaesthesia and the effects of different anaesthetics.

PMID- 17234692
TI  - Dehydration increases L-type Ca(2+) current in rat supraoptic neurons.
AB  - The magnocellular neurosecretory cells of the hypothalamus (MNCs) regulate water
      balance by releasing vasopressin (VP) and oxytocin (OT) as a function of plasma
      osmolality. Release is determined largely by the rate and pattern of MNC firing,
      but sustained increases in osmolality also produce structural adaptations, such
      as cellular hypertrophy, that may be necessary for maintaining high levels of
      neuropeptide release. Since increases in Ca(2+) current could enhance exocytotic
      secretion, influence MNC firing patterns, and activate gene transcription and
      translation, we tested whether Ca(2+) currents in MNCs acutely isolated from the
      supraoptic nucleus (SON) of the hypothalamus are altered by 16-24 h of water
      deprivation. A comparison of whole-cell patch-clamp recordings demonstrated that
      dehydration causes a significant increase in the amplitude of current sensitive
      to the L-type Ca(2+) channel blocker nifedipine (from -56 +/- 6 to -99 +/- 10 pA;
      P < 0.001) with no apparent change in other components of Ca(2+) current. Post
      recording immunocytochemical identification showed that this increase in current
      occurred in both OT- and VP-releasing MNCs. Radioligand binding studies of tissue
      from the SON showed there is also an increase in the density of binding sites for
      an L-type Ca(2+) channel ligand (from 51.5 +/- 4.8 to 68.1 +/- 4.1 fmol (mg
      protein)(-1); P < 0.05), suggesting that there was an increase in the number of L
      type channels on the plasma membrane of the MNCs or some other cell type in the
      SON. There were no changes in the measured number of binding sites for an N-type
      Ca(2+) channel ligand. Dehydration was not associated with changes in the levels
      of mRNA coding for Ca(2+) channel alpha(1) subunits. These data are consistent
      with the hypothesis that a selective increase of L-type Ca(2+) current may
      contribute to the adaptation that occurs in the MNCs during dehydration.

PMID- 17234693
TI  - Bioluminescence imaging of mitochondrial Ca2+ dynamics in soma and neurites of
      individual adult mouse sympathetic neurons.
AB  - Changes in the cytosolic Ca(2+) concentration ([Ca(2+)](c)) are essential for
      triggering neurotransmitter release from presynaptic nerve terminals. Calcium
      induced Ca(2+) release (CICR) from the endoplasmic reticulum (ER) may amplify the
      [Ca(2+)](c) signals and facilitate neurotransmitter release in sympathetic
      neurons. In adrenal chromaffin cells, functional triads are formed by voltage
      operated Ca(2+) channels (VOCCs), CICR sites and mitochondria. In fact,
      mitochondria take up most of the Ca(2+) load entering the cells and are essential
      for shaping [Ca(2+)](c) signals and exocytosis. Here we have investigated the
      existence of such functional triads in sympathetic neurons. The mitochondrial
      Ca(2+) concentration ([Ca(2+)](m)) in soma and neurites of individual mouse
      superior cervical ganglion (SCG) neurons was monitored by bioluminescence imaging
      of targeted aequorins. In soma, Ca(2+) entry through VOCCs evoked rapid, near
      millimolar [Ca(2+)](m) increases in a subpopulation of mitochondria containing
      about 40% of the aequorin. Caffeine evoked a similar [Ca(2+)](m) increase in a
      mitochondrial pool containing about 30% of the aequorin and overlapping with the
      VOCC-sensitive pool. These observations suggest the existence of functional
      triads similar to the ones described in chromaffin cells. In neurites,
      mitochondria were able to buffer [Ca(2+)](c) increases resulting from activation
      of VOCCs but not those mediated by caffeine-induced Ca(2+) release from the ER.
      The weaker Ca(2+) buffering by mitochondria in neurites could contribute to
      facilitate Ca(2+)-induced exocytosis at the presynaptic sites.

PMID- 17234694
TI  - Modulation of Ca(2+) release and Ca(2+) oscillations in HeLa cells and
      fibroblasts by mitochondrial Ca(2+) uniporter stimulation.
AB  - The recent availability of activators of the mitochondrial Ca(2+) uniporter
      allows direct testing of the influence of mitochondrial Ca(2+) uptake on the
      overall Ca(2+) homeostasis of the cell. We show here that activation of
      mitochondrial Ca(2+) uptake by 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5
      triyl)trisphenol (PPT) or kaempferol stimulates histamine-induced Ca(2+) release
      from the endoplasmic reticulum (ER) and that this effect is enhanced if the
      mitochondrial Na(+)-Ca(2+) exchanger is simultaneously inhibited with CGP37157.
      This suggests that both Ca(2+) uptake and release from mitochondria control the
      ability of local Ca(2+) microdomains to produce feedback inhibition of inositol
      1,4,5-trisphosphate receptors (InsP(3)Rs). In addition, the ability of
      mitochondria to control Ca(2+) release from the ER allows them to modulate
      cytosolic Ca(2+) oscillations. In histamine stimulated HeLa cells and human
      fibroblasts, both PPT and kaempferol initially stimulated and later inhibited
      oscillations, although kaempferol usually induced a more prolonged period of
      stimulation. Both compounds were also able to induce the generation of Ca(2+)
      oscillations in previously silent fibroblasts. Our data suggest that cytosolic
      Ca(2+) oscillations are exquisitely sensitive to the rates of mitochondrial
      Ca(2+) uptake and release, which precisely control the size of the local Ca(2+)
      microdomains around InsP(3)Rs and thus the ability to produce feedback activation
      or inhibition of Ca(2+) release.

PMID- 17234695
TI  - D1-like dopamine receptors selectively block P/Q-type calcium channels to reduce
      glutamate release onto cholinergic basal forebrain neurones of immature rats.
AB  - Whole-cell patch-clamp recordings of non-NMDA glutamatergic EPSCs were made from
      identified cholinergic neurones in slices of basal forebrain (BF) of young rats
      (P13-P18), to investigate the subtypes of calcium channels involved in dopamine
      D(1)-like receptor-mediated presynaptic inhibition of the EPSCs. The BF
      cholinergic neurones were pre-labelled by intracerebroventricular injection of a
      fluorescent marker, Cy3-192IgG. A D(1)-like receptor agonist, SKF 81297 (30
      microM) suppressed the EPSCs reversibly by about 30%, and this inhibition was
      reproducible. Calcium channel subtypes involved in the glutamatergic transmission
      were elucidated using selective Ca(2+) channel blockers. The N-type Ca(2+)
      channel blocker omega-conotoxin (omega-CgTX, 3 microM) suppressed the EPSCs by
      57.5%, whereas the P/Q-type channel selective blocker omega-agatoxin-TK (omega
      Aga-TK, 200 nM) suppressed the EPSCs by 68.9%. Simultaneous application of both
      blockers suppressed the EPSCs by 96.1%. The R-type Ca(2+) channel blocker SNX-482
      (300 nM) suppressed the EPSCs by 18.4%, whereas nifedipine, the L-type Ca(2+)
      channel blocker (10 microM), had little effect. In the presence of omega-Aga-TK,
      SKF 81297, a dopamine D(1)-like receptor agonist, had no effect on the EPSCs. On
      the other hand, SKF 81297 could still inhibit the EPSCs in the presence of either
      omega-CgTX, SNX-482 or nifedipine. SKF 81297 had no further effect on the EPSCs
      when external Ca(2+) concentration was raised to 7.2 mM in the presence of omega
      Aga-TK, but could still inhibit the EPSCs in high Ca(2+) solution after omega
      CgTX application. Forskolin (FK, 10 microM), an activator of adenylyl cyclase
      pathway, suppressed the EPSCs, and the FK-induced effect was mostly blocked in
      the presence of omega-Aga-TK but not that of omega-CgTX. These results suggest
      that D(1)-like receptor activation selectively blocks P/Q-type calcium channels
      to reduce glutamate release onto BF cholinergic neurones.

PMID- 17234696
TI  - Brain-computer interfaces: communication and restoration of movement in
      paralysis.
AB  - The review describes the status of brain-computer or brain-machine interface
      research. We focus on non-invasive brain-computer interfaces (BCIs) and their
      clinical utility for direct brain communication in paralysis and motor
      restoration in stroke. A large gap between the promises of invasive animal and
      human BCI preparations and the clinical reality characterizes the literature:
      while intact monkeys learn to execute more or less complex upper limb movements
      with spike patterns from motor brain regions alone without concomitant peripheral
      motor activity usually after extensive training, clinical applications in human
      diseases such as amyotrophic lateral sclerosis and paralysis from stroke or
      spinal cord lesions show only limited success, with the exception of verbal
      communication in paralysed and locked-in patients. BCIs based on
      electroencephalographic potentials or oscillations are ready to undergo large
      clinical studies and commercial production as an adjunct or a major assisted
      communication device for paralysed and locked-in patients. However, attempts to
      train completely locked-in patients with BCI communication after entering the
      complete locked-in state with no remaining eye movement failed. We propose that a
      lack of contingencies between goal directed thoughts and intentions may be at the
      heart of this problem. Experiments with chronically curarized rats support our
      hypothesis; operant conditioning and voluntary control of autonomic physiological
      functions turned out to be impossible in this preparation. In addition to
      assisted communication, BCIs consisting of operant learning of EEG slow cortical
      potentials and sensorimotor rhythm were demonstrated to be successful in drug
      resistant focal epilepsy and attention deficit disorder. First studies of non
      invasive BCIs using sensorimotor rhythm of the EEG and MEG in restoration of
      paralysed hand movements in chronic stroke and single cases of high spinal cord
      lesions show some promise, but need extensive evaluation in well-controlled
      experiments. Invasive BMIs based on neuronal spike patterns, local field
      potentials or electrocorticogram may constitute the strategy of choice in severe
      cases of stroke and spinal cord paralysis. Future directions of BCI research
      should include the regulation of brain metabolism and blood flow and electrical
      and magnetic stimulation of the human brain (invasive and non-invasive). A series
      of studies using BOLD response regulation with functional magnetic resonance
      imaging (fMRI) and near infrared spectroscopy demonstrated a tight correlation
      between voluntary changes in brain metabolism and behaviour.

PMID- 17234697
TI  - Robust correlations between action potential duration and the properties of
      synaptic connections in layer 4 interneurones in neocortical slices from juvenile
      rats and adult rat and cat.
AB  - Many studies of cortical interneurones use immature rodent tissue, while many
      recordings in vivo are made in adult cats. To determine the extent to which
      interneuronal circuitry studied with one approach can transfer to another, we
      compared layer 4 interneurones and their local connections across two age groups
      and two species and with similar connections in layers 3 and 5, using two common
      recording techniques: dual whole cell recordings at 20 degrees C and dual sharp
      electrode recordings at 35 degrees C. In each group, a range of morphological and
      electrophysiological characteristics was observed. In all groups, however,
      positive correlations were found between the width of the action potential and
      rise times and widths at half-amplitude of EPSPs and IPSPs and the EPSP paired
      pulse ratio. Multipolar interneurones with narrow spikes generated the fastest
      IPSPs in pyramidal cells and received the briefest, most strongly depressing
      EPSPs, while bitufted interneurones with broader spikes and adapting and burst
      firing patterns activated the broadest IPSPs and received the slowest, most
      strongly facilitating/augmenting EPSPs. Correlations were similar in all groups,
      with no significant differences between adult rat and cat, or between layers, but
      events were four times slower in juveniles at 20 degrees C. Comparisons with
      previous studies indicate that this is due in part to age, but in large part to
      temperature. Studies in adults were extended with detailed analysis of synaptic
      dynamics, which appeared to decay more rapidly than at juvenile connections.
      EPSPs exhibited the complexity in time course of facilitation, augmentation and
      depression previously described in other adult neocortical connections. That is,
      the time course of recovery from facilitation or depression rarely followed a
      simple smooth exponential decay. Facilitation and depression were not always
      maximal at the shortest interspike intervals, and recovery was often interrupted
      by peaks and troughs in mean EPSP amplitude with a periodicity around 80 Hz.

PMID- 17234698
TI  - Origin of sound-evoked EMG responses in human masseter muscles.
AB  - Sound is a natural stimulus for both cochlear and saccular receptors. At high
      intensities it evokes in active masseter muscles of healthy subjects two
      overlapping reflexes: p11/n15 and p16/n21 waves, whose origin has not yet been
      demonstrated. Our purpose was to test which receptor in the inner ear is
      responsible for these reflexes. We compared masseter EMG responses induced in
      normal subjects (n = 9) by loud clicks (70-100 dB normal hearing level (NHL), 0.1
      ms, 3 Hz) to those evoked in subjects with a selective lesion of the cochlea (n =
      5), of the vestibule (n = 1) or with mixed cochlear-vestibular failure (n = 5).
      In controls, 100 dB clicks induced bilaterally, in the unrectified mean EMG
      (unrEMG), a clear p11 wave followed by a less clear n15 wave and a subsequent n21
      wave. Lowering the intensity to 70 dB clicks abolished the p11/n15 wave, while a
      p16 wave appeared. Rectified mean EMG (rectEMG) showed, at all intensities, an
      inhibitory deflection corresponding to the p16/n21 wave in the unrEMG. Compared
      to controls, all deaf subjects had a normal p11 wave, together with more
      prominent n15 wave; however, the p16/n21 waves, and their corresponding
      inhibition in the rectEMG, were absent. The vestibular patient had bilaterally
      clear p11 waves only when 100 dB clicks were delivered bilaterally or to the
      unaffected ear. Stimulation of the affected ear induced only p16/n21 waves. Data
      from mixed patients were consistent with those of deaf and vestibular patients.
      We conclude that click-induced masseter p11/n15 waves are vestibular dependent,
      while p16/n21 waves depend on cochlear integrity.

PMID- 17234699
TI  - Calpain regulation of AMPA receptor channels in cortical pyramidal neurons.
AB  - AMPA receptors (AMPARs) are the principal glutamate receptors mediating fast
      excitatory synaptic transmission in neurons. Aberrant extracellular glutamate has
      long been recognized as a hallmark phenomenon during neuronal excitotoxicity.
      Excessive glutamate triggers massive Ca(2+) influx through NMDA receptors
      (NMDARs), which in turn can activate Ca(2+)-dependent protease, calpain. In the
      present study, we found that prolonged NMDA treatment (100 microM, 10 min) caused
      a sustained and irreversible suppression of AMPAR-mediated currents in cortical
      pyramidal neurons, which was largely blocked by selective calpain inhibitors.
      Biochemical and immunocytochemical studies demonstrated that in cortical
      cultures, prolonged glutamate or NMDA treatment reduced the level of surface and
      total GluR1, but not GluR2, subunits in a calpain-dependent manner. Consistent
      with the in vitro data, in animals exposed to transient ischaemic insults,
      calpain was strongly activated, and the AMPAR current density and GluR1
      expression level were substantially reduced. Moreover, calpain inhibitors blocked
      the ischaemia-induced depression of AMPAR currents, and the NMDAR-induced,
      calpain-mediated depression of AMPA responses was occluded in ischaemic animals.
      Taken together, our studies show that overstimulation of NMDARs reduces AMPAR
      functions in cortical pyramidal neurons through activation of endogenous calpain,
      and calpain mediates the ischaemia-induced synaptic depression. The down
      regulation of AMPARs by calpain provides a negative feedback to dampen neuronal
      excitability in excitotoxic conditions like ischaemia and epilepsy.

PMID- 17234700
TI  - Placental insufficiency decreases cell cycle activity and terminal maturation in
      fetal sheep cardiomyocytes.
AB  - Umbilicoplacental embolization (UPE) in sheep has been used to investigate the
      effects of placental insufficiency on fetal development. However, its specific
      effects on the heart have been little studied. The aim of this study was to
      determine the effects of placental insufficiency, induced by UPE, on
      cardiomyocyte size, maturation and proliferation. Instrumented fetal sheep
      underwent UPE for either 10 or 20 days. Hearts were collected at 125 +/- 1 days
      (10 day group) or 136 +/- 1 days (20 day group) of gestation (term approximately
      145 days). Cell size, maturational state (as measured by the proportion of
      binucleated myocytes) and cell cycle activity (as measured by positive staining
      of cells for Ki-67) were determined in dissociated cardiomyocytes. UPE fetuses
      were hypoxaemic, but mean arterial pressures were not different from controls.
      UPE fetuses were lighter than control fetuses (10 days: -21%, P < 0.05; 20 days: 
      27%, P < 0.01) and had smaller hearts, but heart weight was appropriate for body
      weight. Neither lengths nor widths were different between control and UPE
      cardiomyocytes at either age. Ten days of UPE did not significantly alter the
      proportion of binucleated myocytes or cell cycle activity in either ventricle.
      However, 20 days of UPE reduced cell cycle activity in both ventricles by
      approximately 70% (P < 0.05); the proportion of binucleated myocytes was also
      lower in UPE fetuses at this age (left ventricle: 31.1 +/- 12.0 versus 46.0 +/-
      6.6%, P < 0.05; right ventricle: 29.4 +/- 12.3 versus 46.3 +/- 5.3%, P < 0.05).
      It is concluded that in the absence of fetal arterial hypertension, placental
      insufficiency is associated with substantially depressed growth of the heart
      through suppressed proliferation and maturation of cardiomyocytes.

PMID- 17234701
TI  - Pathways involved in gut mucosal barrier dysfunction induced in adult rats by
      maternal deprivation: corticotrophin-releasing factor and nerve growth factor
      interplay.
AB  - Neonatal maternal deprivation (NMD) increases gut paracellular permeability (GPP)
      through mast cells and nerve growth factor (NGF), and modifies corticotrophin
      releasing factor (CRF) and corticosterone levels. CRF, corticosterone and mast
      cells are involved in stress-induced mucosal barrier impairment. Consequently,
      this study aimed to specify whether corticosteronaemia and colonic expression of
      both preproCRF and CRF are modified by NMD, and to determine if altered
      expression may participate in the elevated GPP in connection with NGF and mast
      cells. Male Wistar rat pups were either separated from postnatal days 2-14, or
      left undisturbed with their dam. At 12 weeks of age, adult rats were treated with
      mifepristone (an antagonist of corticoid receptors), alpha-helical CRF((9-41)) (a
      non-specific CRF receptor antagonist), or SSR-125543 (CRF-R(1) receptor
      antagonist). We also determined corticosteronaemia and both colonic preproCRF and
      CRF expression. Then, control rats were treated by CRF, doxantrazole (mast cell
      stabilizer), BRX-537A (a mast cell activator) and anti-NGF antibody. NMD did not
      modify colonic CRF level but increased colonic preproCRF expression and
      corticosteronaemia. Peripheral CRF, via CRF-R(1) receptor, but not
      corticosterone, was involved in the elevated GPP observed in these rats, through
      a mast-cell-mediated mechanism, since the increase of GPP induced by exogenous
      CRF was abolished by doxantrazole. Anti-NGF antibody treatment also reduced the
      elevated GPP induced by CRF or BRX-537A. CRF acts through CRF-R(1) receptors to
      stimulate NGF release from mast cells, which participates in the elevated GPP
      observed in NMD adult rats. This suggests that early traumatic experience induced
      neuro-endocrine dysfunction, involved in alterations of gut mucosal barrier.

PMID- 17234702
TI  - Orthodromic spike generation from electrical stimuli in the rat carotid body:
      implications for the afferent spike generation process.
AB  - Carotid body chemoreceptors respond to a decrease in arterial partial pressure of
      O(2) with an increase in sinus nerve action potential (AP) activity which
      initiates a number of protective reflexes. The spike generation process is
      unresolved but is generally considered to be caused by a synaptic depolarizing
      potential (SDP) in the nerve endings caused by release of an excitatory
      transmitter from the glomus cell, which is a secretory cell that is presynaptic
      to the nerve terminals. To detect the purported SDPs, stimulating electrodes were
      placed at sites within the carotid body from which orthodromic APs could be
      evoked at low threshold currents. The probability of AP generation as a function
      of stimulus current was fitted well to a Boltzmann distribution. Subthreshold
      electrical stimuli which were expected to summate with subthreshold SDPs, failed,
      in all instances, to evoke APs at the expected probability. When the stimulus was
      gated to the occurrence of a spontaneous AP, no change in electrical threshold
      was observed as the delay between the spontaneous AP and electrical stimulus was
      increased, despite the presumed disappearance of an SDP in the post-AP period.
      Decreases in spontaneous AP generation rate, caused by hyperoxia, were associated
      with only slight changes in the mean orthodromic stimulus threshold, but with a
      significant increase in slope of the Boltzmann function, suggesting a decrease in
      the variance of nerve terminal excitability during hyperoxia. These results
      suggest that AP generation is not due to SDP events; rather, AP generation is
      likely to be due to a process endogenous to the nerve terminals that modulates
      the variability of nerve terminal excitability.

PMID- 17234704
TI  - Post-inspiratory discharges are the centrepiece of respiratory disrhythmia in a
      gene knockout model of Rett syndrome.

PMID- 17234705
TI  - Fetal programming of cardiovascular diseases in later life - mechanisms beyond
      maternal undernutrition.

PMID- 17234703
TI  - Reliable long-lasting depression interacts with variable short-term facilitation
      to determine corticostriatal paired-pulse plasticity in young rats.
AB  - Synaptic plasticity at corticostraital synapses is proposed to fine tune movment
      and improve motor skills. We found paired-pulse plasticity at corticostriatal
      synapses reflected variably expressed short-term facilitation blended with a
      consistent background of longer-lasting depression. Presynaptic modulation via
      neuotransmitter receptor activation was ruled out as a mechanism for long-lasting
      paired-pulse depression by examining the effect of selective receptor
      antagonists. EPSC amplitude and paired-pulse plasticity, however, was influenced
      by block of D2 dopamine receptors. Block of glutamate transport with l
      transdicarboxylic acid (PDC) reduced EPSCs, possibly through a mechanism of AMPA
      receptor desensitization. Removal of AMPA receptor desensitization with
      cyclothiazide reduced the paired-pulse depression at long-duration interstimulus
      intervals (ISIs), indicating that AMPA receptor desensitization participates in
      corticostriatal paired-pulse plasticity. The low-affinity glutamate receptor
      antagonist cis-2,3-piperidine dicarboxylic acid (PDA) increased paired-pulse
      depression, suggesting that a presynaptic component also exists for long-lasting
      paired-pulse depression. Low Ca(2+)-high Mg(2+) or BAPTA-AM dramatically reduced
      the amplitude of corticostriatal EPSCs and both manipulations increased the
      expression of facilitation and, to a lesser extent, they reduced long-lasting
      paired-pulse depression. EGTA-AM produced a smaller reduction in EPSC amplitude
      and it did not alter paired-pulse facilitation, but in contrast to low Ca(2+) and
      BAPTA-AM, EGTA-AM increased long-lasting paired-pulse depression. These
      experiments suggest that facilitation and depression are sensitive to vesicle
      depletion, which is dependent upon changes in peak Ca(2+) (i.e. low Ca(2+)-high
      Mg(2+) or BAPTA-AM). In addition, the action of EGTA-AM suggests that basal
      Ca(2+) regulates the recovery from long-lasting paired-pulse depression, possibly
      thourgh a Ca(2+)-sensitive process of vesicle delivery.

PMID- 17234706
TI  - p38 mitogen-activated protein kinase mediates palmitate-induced apoptosis but not
      inhibitor of nuclear factor-kappaB degradation in human coronary artery
      endothelial cells.
AB  - Plasma free fatty acids are elevated in patients with type 2 diabetes and
      contribute to the pathogenesis of insulin resistance and endothelial dysfunction.
      The p38 MAPK mediates stress, inflammation, and apoptosis. Whether free fatty
      acids induce apoptosis and/or activate nuclear factor-kappaB inflammatory pathway
      in human coronary artery endothelial cells (hCAECs) and, if so, whether this
      involves the p38 MAPK pathway is unknown. hCAECs (passages 4-6) were grown to 70%
      confluence and then incubated with palmitate at concentrations of 0-300 microm
      for 6-48 h. Palmitate at 100, 200, or 300 microm markedly increased apoptosis
      after 12 h of incubation. This apoptotic effect was time (P=0.008) and dose
      (P=0.006) dependent. Palmitate (100 microm for 24 h) induced a greater than 2
      fold increase in apoptosis, which was accompanied with a 4-fold increase in p38
      MAPK activity (P<0.001). Palmitate did not affect the phosphorylation of Akt1 or
      ERK1/2. SB203580 (a specific inhibitor of p38 MAPK) alone did not affect cellular
      apoptosis; however, it abolished palmitate-induced apoptosis and p38 MAPK
      activation. Palmitate significantly reduced the level of inhibitor of nuclear
      factor-kappaB (IkappaB). However, treatment of cells with SB203580 did not
      restore IkappaB to baseline. We conclude that palmitate induces hCAEC apoptosis
      via a p38 MAPK-dependent mechanism and may participate in coronary endothelial
      injury in diabetes. However, palmitate-mediated IkappaB degradation in hCAECs is
      independent of p38 MAPK activity.

PMID- 17234707
TI  - Characterization of side population in thyroid cancer cell lines: cancer stem
      like cells are enriched partly but not exclusively.
AB  - There is increasing evidence that cancers contain their own stem-like cells
      called cancer stem cells (CSCs). A small subset of cells, termed side population
      (SP), has been identified using flow cytometric analysis. The SP cells have the
      ability to exclude the DNA binding dye, Hoechst33342, and are highly enriched for
      stem cells in many kinds of normal tissues. Because CSCs are thought to be drug
      resistant, SP cells in cancers might contain CSCs. We initially examined the
      presence of SP cells in several human thyroid cancer cell lines. A small
      percentage of SP cells were found in ARO (0.25%), FRO (0.1%), NPA (0.06%), and
      WRO (0.02%) cells but not TPC1 cells. After sorting, the SP cells generated both
      SP and non-SP cells in culture. The clonogenic ability of SP cells was
      significantly higher than that of non-SP cells. Moreover, the SP prevalence was
      dependent on cell density in culture, suggesting that SP cells preferentially
      survived at lower cell density. Microarray experiment revealed differential gene
      expression profile between SP and non-SP cells, and several genes related to
      stemness were up-regulated. However, non-SP population also contained cells that
      were tumorigenic in nude mice, and non-SP cells generated a small number of SP
      cells. These results suggest that cancer stem-like cells are partly, but not
      exclusively, enriched in SP population. Clarifying the key tumorigenic population
      might contribute to the establishment of a novel therapy for thyroid cancer.

PMID- 17234709
TI  - Generation of transgenic rats expressing green fluorescent protein in S-100beta
      producing pituitary folliculo-stellate cells and brain astrocytes.
AB  - Folliculo-stellate (FS) cells are known to act as sustentacular cells or
      scavenger cells in the anterior lobe. However, the precise function and origin of
      FS cells are still under discussion. Like brain astrocytes, FS cells contain S
      100beta protein, and FS cells can be detected immunocytochemically using
      antibodies for S-100beta protein after fixation; however, living FS cells can not
      be detected. The generation of transgenic rats expressing green fluorescent
      protein (GFP) under the control of S-100beta protein gene promoter may allow the
      detection of living FS cells, which may be an excellent tool for the study of FS
      cells. With the aim of generation of transgenic rats, we analyzed the promoter
      activity of the S-100beta gene and found that intron 1 is important for cell
      specific expression of the S-100beta gene. Therefore, we obtained a DNA construct
      containing GFP gene under a part of the S-100 promoter with intron 1. We
      transfected the construct into rat embryos and succeeded in generating transgenic
      rats. The transgenic rats expressed GFP in FS cells specifically in the anterior
      lobe. GFP is also expressed in other known S-100beta-expressing cells, i.e. brain
      astrocytes, adipocytes, and chondrocytes. We believe that the newly generated
      transgenic rats will provide a new approach for the study of FS cells and other S
      100beta protein-producing cells.

PMID- 17234708
TI  - Early aldosterone-regulated genes in cardiomyocytes: clues to cardiac remodeling?
AB  - Recent clinical studies demonstrated beneficial effects of mineralocorticoid
      receptor (MR) antagonists in patients with heart failure and other cardiovascular
      diseases. However, the underlying molecular mechanisms are poorly understood, and
      the genes that mediate direct effects of aldosterone in the cardiovascular system
      are yet to be identified. The goal of this study was to identify genes that are
      directly regulated by aldosterone in cardiomyocytes and thus potentially play a
      role in initiating MR-mediated effects in the heart. We generated clonal cell
      lines of cardiomyocytes (H9C2 cells) stably expressing the MR. Using these cell
      lines and Affymetrix microarrays, we determined the effects of physiological
      concentrations of aldosterone on the gene expression profile. In two independent
      microarrays we identified 48 genes that were induced more than 1.5-fold (27 known
      genes and 21 expressed sequence tags) and five (three known genes and two
      expressed sequence tags) that were suppressed by a 2-h aldosterone treatment. We
      focused on eight genes that have a potential function in cardiovascular
      regulation and verified their aldosterone regulation using quantitative RT-PCR.
      These include genes related to extracellular matrix regulation (tenascin-X,
      ADAMTS1, PAI-1, UPAR, and hyaluronic acid synthase-2), signaling, and regulation
      of vascular tone (RGS2, adrenomedullin) and inflammation (orosomucoid). Protein
      synthesis inhibitors did not prevent aldosterone induction of these genes. We
      conclude that in cardiomyocytes aldosterone rapidly and directly regulates the
      expression of several genes that are involved in cardiac remodeling and
      regulation of blood pressure and thus might be mediators of the physiological and
      pathophysiological effects of aldosterone on the cardiovascular system.

PMID- 17234710
TI  - Localization and activation of glucagon-like peptide-2 receptors on vagal
      afferents in the rat.
AB  - Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent proglucagon-derived
      hormone that stimulates intestinal growth through poorly understood paracrine
      and/or neural pathways. The relationship between GLP-2 action and a vagal pathway
      is unclear. Our aims were to determine whether 1) the GLP-2 receptor (GLP-2R) is
      expressed on vagal afferents by localizing it to the nodose ganglia; 2) exogenous
      GLP-2 stimulates the vagal afferent pathway by determining immunoreactivity for c
      fos protein in the nucleus of the solitary tract (NTS); and 3) functional
      ablation of vagal afferents attenuates GLP-2-mediated intestinal growth in rats
      maintained with total parenteral nutrition (TPN). A polyclonal antibody against
      the N terminus of the rat GLP-2R was raised and characterized. The GLP-2R was
      localized to vagal afferents in the nodose ganglia and confirmed in
      enteroendocrine cells, enteric neurons, and nerve fibers in the myenteric plexus
      using immunohistochemistry. Activation of the vagal afferent pathway, as
      indicated by c-fos protein immunoreactivity in the NTS, was determined by
      immunohistochemistry after ip injection of 200 microg human GLP-2. GLP-2 induced
      a significant 5-fold increase in the number of c-fos protein immunoreactive
      neurons in the NTS compared with saline. Ablation of vagal afferent function by
      perivagal application of capsaicin, a specific afferent neurotoxin, abolished c
      fos protein immunoreactivity, suggesting that activation of the NTS due to GLP-2
      is dependent on vagal afferents. Exogenous GLP-2 prevented TPN-induced mucosal
      atrophy, but ablation of vagal afferent function with capsaicin did not attenuate
      this effect. This suggests that vagal-independent pathways are responsible for
      GLP-2 action in the absence of luminal nutrients during TPN, possibly involving
      enteric neurons or endocrine cells. This study shows for the first time that the
      GLP-2R is expressed by vagal afferents, and ip GLP-2 activates the vagal afferent
      pathway.

PMID- 17234713
TI  - Evidence for anticipatory regulation mediated by drink temperature during fixed
      intensity exercise in the heat.

PMID- 17234711
TI  - A long-acting, mono-PEGylated human growth hormone analog is a potent stimulator
      of weight gain and bone growth in hypophysectomized rats.
AB  - Recombinant human GH is used to treat GH deficiency in children and adults and
      wasting in AIDS patients. GH has a circulating half-life of only a few hours in
      humans and must be administered to patients by daily injection for maximum
      effectiveness. Previous studies showed that longer-acting forms of GH could be
      created by modification of GH with multiple 5-kDa amine-reactive polyethylene
      glycols (PEGs). Eight of nine lysine residues and the N-terminal amino acid were
      modified to varying extents by amine PEGylation of GH. The amine-PEGylated GH
      product comprised a complex mixture of multiple PEGylated species that differed
      from one another in mass, in vitro bioactivity, and in vivo potency. In vitro
      bioactivity of GH was reduced 100- to 1000-fold by extensive amine PEGylation of
      the protein. Here we describe a homogeneously modified, mono-PEGylated GH protein
      that possesses near complete in vitro bioactivity, a long half-life, and
      increased potency in vivo. The mono-PEGylated GH was created by substituting
      cysteine for threonine-3 (T3C) of GH, followed by modification of the added
      cysteine residue with a single 20-kDa cysteine-reactive PEG. The PEG-T3C protein
      has an approximate 8-fold longer half-life than GH after sc administration to
      rats. Every other day or every third day administration of PEG-T3C stimulates
      increases in body weight and tibial epiphysis growth comparable with that
      produced by daily administration of GH in hypophysectomized rats. Long-acting,
      mono-PEGylated GH analogs such as PEG-T3C are promising candidates for future
      testing in humans.

PMID- 17234714
TI  - Effects of indomethacin on systemic and renal haemodynamics in conscious lambs.
AB  - Both prostaglandins (PGs) PGE(2) and PGI(2) can act as renal vasodilators, these
      effects being exacerbated when the renin-angiotensin system is activated.
      Therefore, we hypothesized that PGs would play a more predominant role in
      modulating renal haemodynamics in the newborn period, when the renin-angiotensin
      system is activated. To this end, the role of endogenously produced PGs in
      modulating systemic and renal haemodynamics was investigated in two groups of
      conscious lambs aged approximately 1 and approximately 6 weeks. Arterial
      pressure, venous pressure and renal blood flow were measured for 5 min before
      (control) and for 20 min after intravenous injection of vehicle (experiment 1).
      Twenty-four hours later, this protocol was repeated with intravenous injection of
      the non-selective cyclo-oxygenase inhibitor indomethacin (1 mg kg(-1), experiment
      2). Heart rate was calculated from the systolic peak of the arterial pressure
      waveform, and renal vascular resistance (RVR) was calculated from the measured
      variables. In response to indomethacin but not vehicle, in both age groups of
      lambs there was an increase in mean arterial pressure and pulse interval, as well
      as a marked increase in RVR. These responses to indomethacin were, however,
      transient, with baseline levels being resumed within minutes. Although the
      hypothesis that PGs play a greater role in modulating renal haemodynamics early
      in life is not supported, these data do provide evidence that endogenously
      produced PGs modulate systemic and renal haemodynamics during postnatal
      maturation. It is apparent, however, that other vasoactive factors must be
      rapidly recruited in order to buffer the circulatory responses to removal of
      vasodilatory PGs in the developing newborn.

PMID- 17234715
TI  - Ventilatory control in humans: constraints and limitations.
AB  - Below the lactate threshold ((thetaL)), ventilation (V(E))responds in close
      proportion to CO(2) output to regulate arterial partial pressure of CO(2)
      (PaCO2). While ventilatory control models have traditionally included
      proportional feedback (central and carotid chemosensory) and feedforward (central
      and peripheral neurogenic) elements, the mechanisms involved remain unclear.
      Regardless, putative control schemes have to accommodate the close dynamic
      'coupling' between and V(E) and V(CO2). Above (thetaL), PaCO2 is driven down to
      constrain the fall of arterial pH by a compensatory hyperventilation, probably of
      carotid body origin. When V(E) requirements are high (as in highly fit endurance
      athletes), V(E) can attain limiting proportions. Not only does this impair gas
      exchange at these work rates, but there may be an associated high metabolic cost
      for generation of respiratory muscle power, which may be sufficient to divert a
      fraction of the cardiac output away from the muscles of locomotion to the
      respiratory muscles, further compromising exercise tolerance.

PMID- 17234716
TI  - Prevalence of thyroid antibodies in Nigerian patients.
AB  - BACKGROUND: Thyroid antibody testing is not routinely available in developing
      countries, and few studies have measured thyroid antibodies in Africans. The
      significance of thyroid autoimmunity in an African setting is thus unclear. AIM:
      To determine the prevalence of thyroid antibodies in patients attending a
      Nigerian teaching hospital. DESIGN: Prospective survey. METHODS: We measured
      antibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) using an ELISA
      technique in 104 patients with various thyroid pathologies attending an endocrine
      referral centre in Lagos, Nigeria. Patients were clinically grouped into Graves'
      disease (GD) (n = 69), simple non-toxic goitre (SNTG) (n = 21), toxic nodular
      goitre (TNG) (n = 8) and suspected Hashimoto's thyroiditis (HT) (n = 6). Blood
      donors without thyroid disease (n = 100) acted as controls. RESULTS: TgAb and
      TPOAb were found in 4% and 7%, respectively, of healthy adult controls, 11.6 and
      76.8% of patients with GD, 25% and 12.5% of patients with TNG and 9.52% and
      14.29% of patients with SNTG. TPOAb testing confirmed HT in six patients, and
      identified two further cases that would have been misdiagnosed without antibody
      testing. DISCUSSION: Thyroid autoimmunity appears more common in these Nigerian
      patients than in previous reports from Africa, and TPOAb was significantly
      associated with auto-immune thyroid disease. The clinical utility of these
      antibody measurements requires further evaluation in a wider African population.

PMID- 17234718
TI  - Persistent activation of Rac1 in squamous carcinomas of the head and neck:
      evidence for an EGFR/Vav2 signaling axis involved in cell invasion.
AB  - The poor prognosis associated with head and neck squamous cell carcinoma (HNSCC)
      is primarily due to both local invasion and the regional and/or distant
      metastatic spread. Recent findings have provided evidence that the acquisition of
      a motile and invasive phenotype by cancer cells involves the dysregulated
      function of key intracellular molecular mechanisms together with aberrant
      signaling events initiated by the surrounding microenvironment. These intrinsic
      and extrinsic biochemical pathways in turn often converge to stimulate the
      activity of members of the Rho family of Ras-related guanosine triphosphate (GTP)
      binding proteins, including RhoA, Rac and Cdc42, which control the organization
      of the actin cytoskeleton thereby regulating cell adhesion, polarity and
      motility. In this study, we examined the status of activation of these GTPases in
      a representative collection of HNSCC cell lines. Surprisingly, we found that most
      HNSCC cells exhibit remarkably high levels of GTP-bound Rac1. Further analysis
      revealed that the activation of Rac1 in these HNSCC cells could be due to two
      independent signaling events, an epidermal growth factor receptor (EGFR)-based
      autocrine loop that leads to the activation of the Rac1 exchange factor Vav2 and
      an EGFR/Vav2-independent pathway that arises as a consequence of the oncogenic
      mutation of the H-ras proto-oncogene. Indeed, we provide evidence that the
      EGFR/Vav2/Rac1 axis is a crucial pathway for the acquisition of motile and
      invasive properties of most HNSCC cells. These findings shed light onto the
      molecular mechanisms involved in HNSCC cell invasion, and may reveal new
      therapeutic opportunities to halt the metastatic spread of these aggressive
      malignancies.

PMID- 17234717
TI  - Functional genomics and biochemical characterization of the C. elegans orthologue
      of the Machado-Joseph disease protein ataxin-3.
AB  - Machado-Joseph disease (MJD) is the most common dominant spinocerebellar ataxia.
      MJD is caused by a CAG trinucleotide expansion in the ATXN3 gene, which encodes a
      protein named ataxin-3. Ataxin-3 has been proposed to act as a deubiquitinating
      enzyme in the ubiquitin-proteasome pathway and to be involved in transcriptional
      repression; nevertheless, its precise biological function(s) remains unknown. To
      gain further insight into the function of ataxin-3, we have identified the
      Caenorhabditis elegans orthologue of the ATXN3 gene and characterized its pattern
      of expression, developmental regulation, and subcellular localization. We
      demonstrate that, analogous to its human orthologue, C. elegans ataxin-3 has
      deubiquitinating activity in vitro against polyubiquitin chains with four or more
      ubiquitins, the minimum ubiquitin length for proteasomal targeting. To further
      evaluate C. elegans ataxin-3, we characterized the first known knockout animal
      models both phenotypically and biochemically, and found that the two C. elegans
      strains were viable and displayed no gross phenotype. To identify a molecular
      phenotype, we performed a large-scale microarray analysis of gene expression in
      both knockout strains. The data revealed a significant deregulation of core sets
      of genes involved in the ubiquitin-proteasome pathway, structure/motility, and
      signal transduction. This gene identification provides important clues that can
      help elucidate the specific biological role of ataxin-3 and unveil some of the
      physiological effects caused by its absence or diminished function.

PMID- 17234719
TI  - A review of mechanisms of acrylamide carcinogenicity.
AB  - The fact that acrylamide, a proven rodent carcinogen, is present in significant
      quantities (up to several mg/kg of foodstuff) in a wide range of commonly
      consumed human foods is alarming. Attempts to determine a possible involvement of
      dietary acrylamide in human cancers have not been conclusive, however. To resolve
      the carcinogenicity of acrylamide to humans, the as yet unknown mechanism of
      action of acrylamide needs to be unraveled. The present review is a synopsis of
      research on the known and hypothetical modes of action of acrylamide of relevance
      for carcinogenesis. Both genotoxic and non-genotoxic modes of action of
      acrylamide are discussed with special emphasis on DNA adduct-targeted
      mutagenesis. Mechanistic data are presented from various experimental systems
      including in vitro experiments and in vivo rodent and human studies with special
      focus on mouse models. Human exposure data, including estimates of daily intake
      of dietary acrylamide in different populations and the corresponding cancer risk
      assessments are provided. The significant gaps in knowledge, which currently
      preclude a more definitive evaluation of human cancer risk due to exposure to
      dietary acrylamide, are highlighted. Future directions for research on acrylamide
      and cancer are outlined, and potential challenges are underscored.

PMID- 17234720
TI  - Xanthorrhizol inhibits 12-O-tetradecanoylphorbol-13-acetate-induced acute
      inflammation and two-stage mouse skin carcinogenesis by blocking the expression
      of ornithine decarboxylase, cyclooxygenase-2 and inducible nitric oxide synthase
      through mitogen-activated protein kinases and/or the nuclear factor-kappa B.
AB  - Xanthorrhizol is an active component isolated from Curcuma xanthorrhiza Roxb.
      (Zingiberaceae) that is traditionally used in Indonesia for medicinal purposes.
      In the present study, we found that the topical application of xanthorrhizol
      before 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment significantly
      inhibits TPA-induced mouse ear edema and TPA-induced tumor promotion in 7,12
      dimethylbenz[a]anthracene (DMBA)-initiated ICR mouse skin. The topical
      application of xanthorrhizol following the induction of papillomas with TPA
      induced hyperplasia and dysplasia also reduced tumor multiplicity and incidence
      in DMBA-initiated mouse skin. To further elucidate the molecular mechanisms
      underlying the antitumor-promoting activity of xanthorrhizol, its effect on the
      TPA-induced expression of ornithine decarboxylase (ODC), cyclooxygenase-2 (COX-2)
      and inducible nitric oxide synthase (iNOS) and the upstream signaling molecules
      controlling these proteins were explored in mouse skin. The pre-treatment with
      xanthorrhizol inhibited the expression of ODC, iNOS and COX-2 proteins and
      nuclear factor-kappaB (NF-kappaB) activation in both mouse skin with TPA-induced
      acute inflammation and DMBA-initiated mouse skin promoted by TPA for 19 weeks.
      When mouse skin was treated after TPA-induced production of papillomas,
      xanthorrhizol remarkably suppressed the expression of ODC, iNOS and COX-2 and
      inhibited the activation of NF-kappaB. Furthermore, western blot analysis showed
      that xanthorrhizol suppressed the activation of extracellular signal-regulated
      protein kinase, p38, c-Jun-N-terminal kinase and Akt in mice after topical
      application for 6 weeks following the induction of papillomas. Taken together,
      the present study demonstrates that xanthorrhizol not only delays or inhibits
      tumor formation, but also reverses the carcinogenic process at pre-malignant
      stages by reducing the protein levels of ODC, iNOS and COX-2 regulated by the NF
      kappaB, mitogen-activated protein kinases and/or Akt.

PMID- 17234721
TI  - Soy phytochemicals synergistically enhance the preventive effect of tamoxifen on
      the growth of estrogen-dependent human breast carcinoma in mice.
AB  - The objective of this work was to determine the interactive effects between soy
      bioactive components and tamoxifen (TAM) on prevention of estrogen-dependent
      breast cancer (BRCA). We initially investigated the effects of soy isoflavone
      genistein and TAM on the growth and cell cycle progression of estrogen-dependent
      MCF-7 human BRCA cells, and on the expression of ERalpha, pS2 and EGFR genes in
      vitro. Genistein or TAM alone inhibited the growth of MCF-7 cells in part via
      G(1) phase arrest, but their combinations showed suggestive antagonistic effects.
      We further evaluated the effects of bioactive soy components and TAM on the
      growth inhibition of MCF-7 tumors in a clinically relevant breast tumor model.
      TAM and bioactive soy components, genistein and soy phytochemical concentrate
      (SPC), delayed the growth of MCF-7 tumors. The combination of TAM with genistein
      or SPC, especially at the lower dose of TAM, had synergistic effects on delaying
      the growth of MCF-7 tumors. Biomarker determination suggests that the combination
      of TAM and soy components may synergistically delay the growth of MCF-7 tumors
      via their combined effects on induction of tumor cell apoptosis and inhibition of
      tumor cell proliferation. In addition, genistein and TAM combination
      synergistically delayed the growth of breast tumor via decreased estrogen level
      and activity, and down-regulation of EGFR expression. The results from our
      studies suggest that further investigations may be warranted to determine if the
      combination of TAM and bioactive soy components may be used for prevention and/or
      treatment of estrogen-dependent BRCA.

PMID- 17234722
TI  - Amino acid substitution polymorphisms of the DNA repair gene MGMT and the
      susceptibility to cervical carcinoma.
AB  - In the current study, we examined the association between polymorphisms in the
      O(6)-methylguanine-DNA methyltransferase gene (MGMT) and the risk for cervical
      carcinoma. We prospectively selected 1012 patients, including 539 with carcinoma
      and 473 with cervical intra-epithelial neoplasia and 800 healthy women from five
      hospitals in Zhejiang Province, China. Three single-nucleotide polymorphisms
      (Leu84Phe, Ile143Val and Lys178Arg) were genotyped, and their association with
      other epidemiological risk factors was examined. Compared with the MGMT Lys178Lys
      (AA) or Ile143Ile (AA) genotypes, women homozygous for the Arg178Arg (GG) or Val
      143Val (GG) genotypes had a significantly increased risk for cervical carcinoma
      both in the overall carcinoma group and in the high-risk human papillomavirus
      positive group. Compared with using Leu84Leu (CC), Phe84Phe (TT) and Leu84Phe
      (CT) which did not increase the risk for cervical carcinoma. In addition, using
      84Leu (C)-143Ile (A)-178Lys (A) as reference, women carrying 84Phe (T)-143Val (G)
      178Arg (G) had a 1.87-fold higher risk for cervical carcinoma (95% confidence
      interval 1.07-3.27). Similar results were observed for squamous cell carcinomas.
      The effect of the combination of Arg178Arg (GG) and Lys178Arg (AG) genotypes and
      the 84Phe (T)-143Val (G)-178Arg (G) haplotype was more pronounced in women
      infected with high-risk human papillomavirus, an early onset of sexual activity,
      multiple sexual partners, an early age of the first full-term pregnancy and high
      parity. These findings suggest that polymorphism in MGMT increases the
      susceptibility of women to cervical carcinoma, especially in those with high-risk
      sexual and reproductive histories.

PMID- 17234723
TI  - Trans-fatty acid intake and increased risk of advanced prostate cancer:
      modification by RNASEL R462Q variant.
AB  - Previous studies have examined the role of higher trans-fatty acid consumption on
      prostate cancer risk, but the results remain unclear. Any potential association
      may be modified by variants in genes involved with immune and inflammatory
      responses. To investigate this, we undertook a case-control study (N = 1012) of
      the association between trans-fatty acid intake and advanced prostate cancer, and
      evaluated whether this effect was modified by a functional polymorphism in the
      RNASEL gene (R462Q). Among Caucasians (N = 834), we observed that each type of
      trans-fatty acid and total trans-fatty acid intake showed a statistically
      significant positive association with prostate cancer, but only weakly increased
      risk for the isomers of cis-fatty acids. Compared with the lowest quartile of
      total trans-fatty acid consumption, the higher quartiles gave odds ratios (ORs)
      equal to 1.58 [95% confidence interval (CI): 1.00, 2.48], 1.95 (95% CI: 1.20,
      3.19) and 2.77 (95% CI: 1.60, 4.79) (P-trend = 0.0003); this effect was modified
      by the RNASEL R462Q polymorphism (P(interaction) = 0.01). Among men with the
      QQ/RQ genotype, the association between total trans-fatty acid intake and
      prostate cancer was substantially stronger [ORs of higher quartiles equal to 2.93
      (95% CI: 1.62, 5.30), 3.13 (95% CI: 1.64, 5.98) and 4.80 (95% CI: 2.29, 10.08),
      respectively]. For men with the RR genotype, total trans-fatty acid intake was
      not associated with disease. This suggests that among Caucasians, positive
      association between higher trans-fatty acid consumption and prostate cancer may
      be modified by the functional RNASEL variant R462Q.

PMID- 17234724
TI  - Pro/antioxidant status and AP-1 transcription factor in murine skin following
      topical exposure to cumene hydroperoxide.
AB  - Organic peroxides, widely used in the chemical and pharmaceutical industries, can
      act as skin tumor promoters and cause epidermal hyperplasia. They are also known
      to trigger free radical generation. The present study evaluated the effect of
      cumene hydroperoxide (Cum-OOH) on the induction of activator protein-1 (AP-1),
      which is linked to the expression of genes regulating cell proliferation, growth
      and transformation. Previously, we reported that topical exposure to Cum-OOH
      caused formation of free radicals and oxidative stress in the skin of vitamin E
      deficient mice. The present study used JB6 P+ mouse epidermal cells and AP-1
      luciferase reporter transgenic mice to identify whether exposure to Cum-OOH
      caused activation of AP-1, oxidative stress, depletion of antioxidants and tumor
      formation during two-stage carcinogenesis. In vitro studies found that exposure
      to Cum-OOH reduced the level of glutathione (GSH) in mouse epidermal cells (JB6
      P+) and caused the induction of AP-1. Mice primed with dimethyl-benz[a]anthracene
      (DMBA) were topically exposed to Cum-OOH (82.6 micromol) or the positive control,
      12-O-tetradecanoylphorbol-13-acetate (TPA, 17 nmol), twice weekly for 29 weeks.
      Activation of AP-1 in skin was detected as early as 2 weeks following Cum-OOH or
      TPA exposure. No AP-1 expression was found 19 weeks after initiation. Papilloma
      formation was observed in both the DMBA-TPA- and DMBA-Cum-OOH-exposed animals,
      whereas skin carcinomas were found only in the DMBA-Cum-OOH-treated mice. A
      greater accumulation of peroxidative products (thiobarbituric acid-reactive
      substances), inflammation and decreased levels of GSH and total antioxidant
      reserves were also observed in the skin of DMBA-Cum-OOH-exposed mice. These
      results suggest that Cum-OOH-induced carcinogenesis is accompanied by increased
      AP-1 activation and changes in antioxidant status.

PMID- 17234725
TI  - Exercise training restores coronary arteriolar dilation to NOS activation distal
      to coronary artery occlusion: role of hydrogen peroxide.
AB  - OBJECTIVE: Exercise training has been shown to restore vasodilation to nitric
      oxide synthase (NOS) activation in arterioles distal to coronary artery
      occlusion. Because reactive oxygen species are generated during NOS uncoupling
      and the production of vasodilator H2O2 is increased during exercise in patients
      with coronary disease, we proposed that H2O2 may contribute to the restoration of
      vasodilation in porcine coronary occlusion model. METHODS AND RESULTS: Left
      circumflex (LCX) coronary artery of miniature swine was progressively occluded
      for 8 weeks followed by exercise training (EX; 5 days/wk treadmill) or sedentary
      (SED) protocols for 12 weeks. Arterioles were isolated from distal LCX and
      nonoccluded left anterior descending (LAD) artery for in vitro study.
      Vasodilation to NOS activators adenosine and ionomycin was impaired in SED LCX,
      but not LAD, arterioles. This impairment was restored by L-arginine. NO
      production induced by adenosine was also reduced in SED LCX arterioles. EX had no
      effect on LAD arterioles but improved NO production and restored dilation of LCX
      arterioles. NOS blockade (L-NAME) inhibited vasodilation to NOS activators in LAD
      (SED & EX) arterioles but was ineffective in SED LCX arterioles. In EX LCX
      arterioles, vasodilation to NOS activators was slightly inhibited by L-NAME but
      abolished by catalase. H2O2 production was markedly increased by adenosine in EX
      LCX arterioles. CONCLUSIONS: This study demonstrates that endothelium-dependent
      NO-mediated dilation is impaired in SED LCX arterioles and that EX training
      restores the impaired function. It appears that H2O2, in addition to NO,
      contributes significantly to EX-induced restoration of endothelium-dependent
      dilation of coronary arterioles distal to occlusion.

PMID- 17234726
TI  - Angiotensin II induces endothelial xanthine oxidase activation: role for
      endothelial dysfunction in patients with coronary disease.
AB  - OBJECTIVE: Xanthine oxidase (XO), a major source of superoxide, has been
      implicated in endothelial dysfunction in atherosclerosis. Mechanisms, however,
      leading to endothelial XO activation remain poorly defined. We tested the effect
      of angiotensin II (Ang II) on endothelial XO and its relevance for endothelial
      dysfunction in patients with coronary disease. METHODS AND RESULTS: XO protein
      levels and XO-dependent superoxide production were determined in cultured
      endothelial cells in response to Ang II. In patients with coronary disease,
      endothelium-bound XO activity as determined by ESR spectroscopy and endothelium
      dependent vasodilation were analyzed before and after 4 weeks of treatment with
      the AT1-receptor blocker losartan, the XO inhibitor allopurinol, or placebo. Ang
      II substantially increased endothelial XO protein levels and XO-dependent
      superoxide production in cultured endothelial cells, which was prevented by
      NAD(P)H-oxidase inhibition. In vivo, endothelium-bound XO activity was reduced by
      losartan and allopurinol, but not placebo therapy in patients with coronary
      disease. XO inhibition with oxypurinol improved endothelium-dependent
      vasodilation before, but not after losartan or allopurinol therapy. CONCLUSIONS:
      These findings suggest a novel mechanism whereby Ang II promotes endothelial
      oxidant stress, ie, by redox-sensitive XO activation. In patients with coronary
      disease, losartan therapy reduces endothelium-bound XO activity likely
      contributing to improved endothelial function.

PMID- 17234728
TI  - Cysteine-674 of the sarco/endoplasmic reticulum calcium ATPase is required for
      the inhibition of cell migration by nitric oxide.
AB  - OBJECTIVES: Nitric oxide inhibits smooth muscle cell migration after arterial
      injury, but the detailed mechanism is not fully understood. The sarco/endoplasmic
      reticulum calcium ATPase (SERCA) lowers cell Ca2+ by increasing intracellular
      Ca2+ uptake and inhibiting extracellular Ca2+ influx. Our previous studies showed
      that NO causes cyclic GMP-independent arterial relaxation by increasing SERCA
      activity by inducing reversible S-glutathiolation at cysteine-674. Because Ca2+
      is an important second messenger for cell migration, we hypothesized that NO also
      inhibits cell migration through redox regulation of SERCA activity via cysteine
      674. METHODS AND RESULTS: To test our hypothesis, overexpression of either wild
      type (WT) or mutant SERCA in which cysteine-674 was mutated to serine was
      accomplished by stable transfection of HEK 293 or adenoviral expression in rat
      aortic smooth muscle cells (VSMCs). In the cell models expressing mutant SERCA,
      biotinylated-iodoacetamide (BIAM) and biotinylated-glutathione labeling of SERCA
      was decreased, and NO failed to increase SERCA activity or decrease Ca2+ influx,
      thus validating that the expression of mutant SERCA prevents its redox-dependent
      activation. In the absence of NO, fetal bovine serum stimulated migration of both
      cell types expressing WT or C674S SERCA at similar rates. The NO donor S
      nitrosopenicillamine inhibited migration of cells with WT SERCA, but had no
      effect on the migration of either HEK cells or VSMCs with C674S SERCA. The same
      result was obtained in VSMCs in which endogenous NO was produced by iNOS induced
      by interleukin (IL)-1beta. Blocking cyclic GMP did not prevent the inhibition of
      migration by NO. CONCLUSIONS: In cells overexpressing SERCA, the cyclic GMP
      independent, redox regulation of SERCA cysteine-674 is required for the
      inhibition of cell migration by both exogenous and endogenously generated NO.

PMID- 17234727
TI  - Mineralocorticoid receptor activation promotes vascular cell calcification.
AB  - OBJECTIVE: Clinical studies demonstrate that mineralocorticoid receptor (MR)
      antagonism improves outcomes in cardiovascular patients and that vascular
      calcification correlates with adverse cardiac events. We have recently
      demonstrated that human vascular smooth muscle cells (VSMCs) express functional
      MRs that, in response to aldosterone, modulate expression of osteogenic genes
      including alkaline phosphatase (ALP) and bone morphogenetic protein-2 (BMP2).
      This study examines the effects of MR activation by aldosterone on the process of
      in vitro vascular calcification. METHODS AND RESULTS: Using immunoblotting and
      adenoviral promoter-reporter assays, we demonstrated that calcifying vascular
      cells (CVCs), an in vitro model of vascular calcification, express MRs that
      mediate both aldosterone- and cortisol-stimulated gene transcription. In this
      model, aldosterone stimulated ALP activity, an early marker of osteoblastic
      differentiation, as well as mineralization. Aldosterone antagonism with
      spironolactone abolished both effects implicating CVC MRs in the mechanism of
      aldosterone-stimulated vascular calcification. Inhibition of BMP2 signaling by
      overexpression of dominant negative BMP2 receptor did not attenuate aldosterone
      induced osteoblastic differentiation. CONCLUSIONS: Aldosterone activation of MR
      promotes osteoblastic differentiation and mineralization of VSMCs independent of
      BMP2 signaling. These data provide a mechanistic link between hormone-mediated
      VSMC MR activation and vascular calcification, two processes associated with
      increased risk of cardiovascular ischemic events in humans.

PMID- 17234729
TI  - Cell-free mRNA concentrations of plasminogen activator inhibitor-1 and tissue
      type plasminogen activator are increased in the plasma of pregnant women with
      preeclampsia.
AB  - BACKGROUND: Detection of placental mRNA in maternal plasma has been reported in
      high-risk pregnancies. We attempted to investigate the concentrations of
      plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator
      (tPA) mRNA in maternal plasma in preeclampsia. METHODS: Peripheral blood samples
      were obtained from healthy pregnant women before and after delivery and also from
      women with or without preeclampsia. Plasma was isolated from these samples, and
      RNA was extracted. Plasma PAI-1 and tPA mRNA concentrations were then measured by
      use of reverse transcription PCR assays. The concentrations were converted into
      multiples of the median (MoM) of the controls adjusted for gestational age. Data
      were stratified and analyzed according to the clinical severity of preeclampsia
      and quantitative distribution of blood pressure and proteinuria. RESULTS: The
      median (minimum-maximum) PAI-1 mRNA MoM values for women with preeclampsia and
      controls were 2.48 (0.82-8.53) and 1.00 (0.41-2.33), respectively, whereas the
      median (minimum-maximum) tPA mRNA MoM values were 3.33 (1.01-10.58) and 1.00
      (0.95-1.20), respectively. The concentrations of both PAI-1 and tPA mRNA were
      significantly increased in cases of preeclampsia, compared with controls (P
      <0.0001). The MoM values of both mRNA species were directly correlated with the
      severity of preeclampsia and were greatest among a subgroup of hemolysis,
      increased liver enzymes, and low platelets pregnancies. CONCLUSION: Maternal
      plasma PAI-1 and tPA mRNAs are significantly increased in patients with
      preeclampsia and are positively correlated with the severity of preeclampsia.

PMID- 17234730
TI  - High-dose alpha-tocopherol therapy does not affect HDL subfractions in patients
      with coronary artery disease on statin therapy.
AB  - BACKGROUND: Subfractions of HDL, particularly large HDL (HDL2), are inversely
      correlated with the severity of coronary artery disease (CAD). alpha-Tocopherol
      (AT) is the main lipid-soluble antioxidant in plasma. Results of a previous small
      study (n = 44) suggested that either a combination of an antioxidant cocktail
      [800 IU/day 2R,4'R,8'R-(RRR)-AT plus 1 g vitamin C, 25 mg beta-carotene, and 100
      microg selenium] or individual antioxidant vitamins combined with simvastatin
      niacin (S-N) therapy attenuated the protective increase in HDL2 seen with S-N
      alone. Few data are available on the effect of AT therapy alone on HDL
      subfractions, which we addressed in this study. METHODS: In a prospective placebo
      controlled study, we randomized 127 patients with stable CAD to receive high-dose
      RRR-AT (1200 IU/day for 2 years) or placebo. HDL subfractions (small, medium, and
      large HDL particles) were analyzed by nuclear magnetic resonance spectroscopy.
      RESULTS: AT concentrations significantly increased in the AT arm but not with
      placebo. No differences were noted between AT and placebo groups in
      concentrations of total cholesterol, triglyceride, LDL-cholesterol, or HDL
      cholesterol. AT therapy did not affect total, small, medium, or large HDL
      particles compared with baseline or placebo. Furthermore, serum apolipoprotein A1
      concentrations did not change after 2 years AT therapy as compared with baseline.
      CONCLUSIONS: High-dose AT therapy administered for a 2-year period does not
      negatively affect either HDL subfractions or apolipoprotein A1 in patients with
      CAD on statin therapy. Thus the negative interaction previously proposed between
      antioxidant cocktail and statin therapy cannot be attributed to AT.

PMID- 17234731
TI  - A simple method for DNA isolation from clotted blood extricated rapidly from
      serum separator tubes.
AB  - BACKGROUND: After clinical laboratory tests have been performed, it can be
      difficult to obtain DNA without further patient involvement. Although the blood
      clot remaining within the serum-separation tube after serum collection is a
      source of DNA, recovery of the clot from the tube is a significant challenge.
      METHOD: We devised a method to efficiently remove clotted blood from the serum
      separation gel and extract DNA from clotted whole blood samples, obtaining
      maximum yield of the DNA without DNA contamination by the separation gel. The
      method involved centrifugation of the sample in the inverted original 10-mL
      collection tube to displace the separation gel for easy isolation of the blood
      clot and shearing of the blood clot by centrifugation through a 20-gauge wire
      mesh cone at 2000 g in a swinging-bucket rotor. After erythrocyte lysis and
      proteinase-K digestion of the fragmented clot, DNA was precipitated with
      isopropanol in the presence of glycogen. RESULTS: The mean amount of DNA obtained
      from a 4-mL clotted blood sample prepared by this method was 37.1 microg for
      clots processed soon after collection, with a reduction to 0.439 microg for clots
      stored for 1 month before extraction. The quality of the DNA was comparable to
      that extracted directly from whole blood, and it was found to be suitable for PCR
      mediated analysis. CONCLUSION: We have formulated a method that overcomes the
      difficulties of safely extricating a blood clot from serum-separation tubes,
      allowing rapid DNA extraction for the purposes of genetic investigation.

PMID- 17234732
TI  - Relationships of circulating carotenoid concentrations with several markers of
      inflammation, oxidative stress, and endothelial dysfunction: the Coronary Artery
      Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in
      Antioxidants (YALTA) study.
AB  - BACKGROUND: Serum carotenoid concentrations relate inversely to cardiovascular
      disease incidence. To clarify the effect of carotenoids on atherosclerotic risk
      factors, we examined the association of circulating carotenoids with
      inflammation, oxidative stress, endothelial dysfunction, and smoking. METHODS:
      Black and white men and women in the Coronary Artery Risk Development in Young
      Adults study, ages 18 to 30 years at recruitment (1985-1986) from 4 US cities,
      were investigated over 15 years. We included 2048 to 4580 participants in
      analyses of the sum of serum alpha-carotene, beta-carotene, zeaxanthin/lutein,
      and beta-cryptoxanthin concentrations and of lycopene at year 0 and at year 7.
      RESULTS: The year 0 sum of 4 carotenoids was inversely associated (all P <0.05)
      with year 0 leukocyte count (slope per sum carotenoid SD, -0.17); year 7
      fibrinogen (slope, -0.10); year 7 and year 15 C-reactive protein (slope, -0.12
      and -0.09); and year 15 F(2)-isoprostanes (slope, -13.0), soluble P-selectin
      (slope, -0.48), and soluble intercellular adhesion molecule-1 (sICAM1; slope, 
      5.1). Leukocyte counts and sICAM1 and F(2)-isoprostane concentrations had
      stronger associations in smokers than in nonsmokers, and sICAM1 concentrations
      were higher in the highest carotenoid quartile in smokers than in the lowest
      carotenoid quartile in nonsmokers. Superoxide dismutase was positively associated
      with the sum of 4 carotenoids (slope, 0.12; P <0.01). Lycopene was inversely
      associated only with sICAM1. The year 7 carotenoid associations with these
      markers were mostly similar to those at year 0. CONCLUSIONS: Circulating serum
      carotenoids were associated, some interactively with smoking, in apparently
      beneficial directions with markers of inflammation, oxidative stress, and
      endothelial dysfunction.

PMID- 17234733
TI  - Simple method for haplotyping the poly(TG) repeat in individuals carrying the
      IVS8 5T allele in the CFTR gene.
AB  - BACKGROUND: The 5T allele of the polyT tract located within intron 8 of the
      cystic fibrosis transmembrane conductance regulator (CFTR) gene is a variant that
      in trans with a severe CFTR mutation can result in normal phenotype, congenital
      bilateral absence of vas deferens (CBAVD), or mild cystic fibrosis. The 5T allele
      has been associated with the skipping of exon 9, a process that seems to be
      influenced by an adjacent 9-13TG tandem repeat. The 12- or 13TG repeats are often
      associated with an abnormal phenotype. We present here a single-step method for
      direct haplotyping of the TG repeats in 5T carriers. METHOD: The method is based
      on a single-step PCR, using a fluorescently labeled forward primer and a reverse
      allele-specific primer matching the 5T allele. We validated the test in 30
      control samples of known 5T-poly(TG) haplotype and then used this method to
      evaluate 57 clinical samples. RESULTS: The expected TG genotypes were obtained
      for all 5T control samples, and no nonspecific amplification of either the 7T or
      9T alleles was detected. In our 5T-positive collection 9 of 9 (100%) CBAVD
      patients, 6 of 12 (50.0%) chronic pancreatitis patients, and 12 of 36 (33.3%)
      individuals undergoing assisted reproduction showed 5T-12TG haplotype.
      CONCLUSIONS: Our method is an accurate, specific, and simple tool to characterize
      the 5T poly(TG) haplotype. Our results confirm the high frequency of 5T-12TG in
      CBAVD patients and do not preclude a potential effect also in pancreatitis. This
      assay can be useful in assessment of the disease risk in 5T carriers.

PMID- 17234734
TI  - Temporal genetic program following B-cell receptor cross-linking: altered balance
      between proliferation and death in healthy and malignant B cells.
AB  - Gene expression in cells is a dynamic process but is usually examined at a single
      time point. We used gene expression profiling over time to build temporal models
      of gene transcription after B-cell receptor (BCR) signaling in healthy and
      malignant B cells and chose this as a model since BCR cross-linking induces both
      cell proliferation and apoptosis, with increased apoptosis in chronic lymphocytic
      leukemia (CLL) compared to healthy B cells. To determine the basis for this, we
      examined the global temporal gene expression profile for BCR stimulation and
      developed a linear combination method to summarize the effect of BCR simulation
      over all the time points for all patients. Functional learning identified common
      early events in healthy B cells and CLL cells. Although healthy and malignant B
      cells share a common genetic pattern early after BCR signaling, a specific
      genetic program is engaged by the malignant cells at later time points after BCR
      stimulation. These findings identify the molecular basis for the different
      functional consequences of BCR cross-linking in healthy and malignant B cells.
      Analysis of gene expression profiling over time may be used to identify genes
      that might be rational targets to perturb these pathways.

PMID- 17234735
TI  - The molecular basis of IL-21-mediated proliferation.
AB  - Interleukin-21 (IL-21) is a type I cytokine that modulates functions of T, B,
      natural killer (NK), and myeloid cells. The IL-21 receptor (IL-21R) is closely
      related to the IL-2 receptor beta chain and is capable of transducing signals
      through its dimerization with the common cytokine receptor gamma chain
      (gamma(c)), the protein whose expression is defective in humans with X-linked
      severe combined immunodeficiency. To clarify the molecular basis of IL-21
      actions, we investigated the role of tyrosine residues in the IL-21R cytoplasmic
      domain. Simultaneous mutation of all 6 tyrosines greatly diminished IL-21
      mediated proliferation, whereas retention of tyrosine 510 (Y510) allowed full
      proliferation. Y510 efficiently mediated IL-21-induced phosphorylation of Stat1
      and Stat3, but not of Stat5, and CD8(+) T cells from Stat1/Stat3 double knock-out
      mice exhibited decreased proliferation in response to IL-21 + IL-15. In addition,
      IL-21 weakly induced phosphorylation of Shc and Akt, and consistent with this,
      specific inhibitors of the MAPK and PI3K pathways inhibited IL-21-mediated
      proliferation. Collectively, these data indicate the involvement of the Jak-STAT,
      MAPK, and PI3K pathways in IL-21 signaling.

PMID- 17234736
TI  - The C/EBPdelta tumor suppressor is silenced by hypermethylation in acute myeloid
      leukemia.
AB  - Aberrant DNA methylation is the most frequent molecular alteration in acute
      myeloid leukemia (AML). To identify methylation-silenced genes in AML, we
      performed microarray analyses in U937 cells exposed to the demethylating agent 5
      aza-deoxy-cytidine. Overall, 274 transcripts were significantly induced.
      Interestingly, C/EBPdelta expression was significantly induced (more than 10
      fold) by demethylation whereas expression of all other C/EBP family members
      remained unchanged. The C/EBPdelta promoter was strongly methylated in different
      leukemic cell lines and showed signs of a repressed chromatin state. Analyses of
      the promoter regions of the entire C/EBP family (alpha, beta, gamma, delta,
      epsilon, zeta) in bone marrow samples from AML patients (n = 80) and controls (n
      = 15) by mass spectrometry revealed that C/EBPdelta is the most commonly
      hypermethylated C/EBP gene in AML. Hypermethylation occurred in more than 35% of
      AML patients at primary diagnosis. A significant correlation (P = .016) was
      observed between hypermethylation of the C/EBPdelta promoter and low expression
      of C/EBPdelta in AML patients. C/EBPdelta promoter activity was strongly
      repressed by methylation in vitro, and transcriptional repression partially
      depended on MeCP2 activity. C/EBPdelta exhibited growth-inhibitory properties in
      primary progenitor cells as well as in Flt3-ITD-transformed cells. Taken
      together, C/EBPdelta is a novel tumor suppressor gene in AML that is silenced by
      promoter methylation.

PMID- 17234737
TI  - How I treat refractory acute GVHD.
AB  - Graft-versus-host disease (GVHD) after allogeneic hematopoietic cell
      transplantation (HCT) is associated with considerable morbidity and mortality,
      particularly in patients who do not respond to primary therapy, which usually
      consists of glucocorticoids (steroids). Approaches to therapy of acute GVHD
      refractory to "standard" doses of steroids have ranged from increasing the dose
      of steroids to the addition of polyclonal or monoclonal antibodies, the use of
      immunotoxins, additional immunosuppressive/chemotherapeutic interventions,
      phototherapy, and other means. While many pilot studies have yielded encouraging
      response rates, in most of these studies long-term survival was not improved in
      comparison with that seen with the use of steroids alone. A major reason for
      failure has been the high rate of infections, including invasive fungal,
      bacterial, and viral infections. It is difficult to conduct controlled
      prospective trials in the setting of steroid-refractory GVHD, and a custom
      tailored therapy dependent upon the time after HCT, specific organ manifestations
      of GVHD, and severity is appropriate. All patients being treated for GVHD should
      also receive intensive prophylaxis against infectious complications.

PMID- 17234739
TI  - HOXA10 is a critical regulator for hematopoietic stem cells and
      erythroid/megakaryocyte development.
AB  - The Homeobox (Hox) transcription factors are important regulators of normal and
      malignant hematopoiesis because they control proliferation, differentiation, and
      self-renewal of hematopoietic cells at different levels of the hematopoietic
      hierarchy. In transgenic mice we show that the expression of HOXA10 is tightly
      regulated by doxycycline. Intermediate concentrations of HOXA10 induced a 15-fold
      increase in the repopulating capacity of hematopoietic stem cells (HSCs) after 13
      days of in vitro culture. Notably, the proliferation induction of HSC by HOXA10
      was dependent on the HOXA10 concentration, because high levels of HOXA10 had no
      effect on HSC proliferation. Furthermore, high levels of HOXA10 blocked erythroid
      and megakaryocyte development, demonstrating that tight regulation of HOXA10 is
      critical for normal development of the erythroid and megakaryocytic lineages. The
      HOXA10-mediated effects on hematopoietic cells were associated with altered
      expression of genes that govern stem-cell self-renewal and lineage commitment
      (eg, hepatic leukemia factor [HlF], Dickkopf-1 [Dkk-1], growth factor independent
      1 [Gfi-1], and Gata-1). Interestingly, binding sites for HOXA10 were found in
      HLF, Dkk-1, and Gata-1, and Dkk-1 and Gfi-1 were transcriptionally activated by
      HOXA10. These findings reveal novel molecular pathways that act downstream of
      HOXA10 and identify HOXA10 as a master regulator of postnatal hematopoietic
      development.

PMID- 17234738
TI  - Prognostic impact of elevated pretransplantation serum ferritin in patients
      undergoing myeloablative stem cell transplantation.
AB  - Iron overload could be a significant contributor to treatment-related mortality
      (TRM) for patients with hematologic malignancies undergoing hematopoietic stem
      cell transplantation (HSCT). We studied 590 patients who underwent myeloablative
      allogeneic HSCT at our institution, and on whom a pretransplantation serum
      ferritin was available. An elevated pretransplantation serum ferritin level was
      strongly associated with lower overall and disease-free survival. Subgroup
      multivariable analyses demonstrated that this association was restricted to
      patients with acute leukemia or myelodysplastic syndrome (MDS); in the latter
      group, the inferior survival was attributable to a significant increase in TRM.
      There was also a trend toward an increased risk of veno-occlusive disease in
      patients with high ferritin. Our results argue that iron overload plays an
      important role in transplantation outcome for patients with acute leukemia or
      MDS, as it does in thalassemia. They also suggest future prospective trials to
      examine the potential benefit of chelation therapy in this setting.

PMID- 17234740
TI  - A novel role for PECAM-1 in megakaryocytokinesis and recovery of platelet counts
      in thrombocytopenic mice.
AB  - During thrombopoiesis, maturing megakaryocytes (MKs) migrate within the complex
      bone marrow stromal microenvironment from the proliferative osteoblastic niche to
      the capillary-rich vascular niche where proplatelet formation and platelet
      release occurs. This physiologic process involves proliferation, differentiation,
      migration, and maturation of MKs before platelet production occurs. In this
      study, we report a role for the glycoprotein PECAM-1 in thrombopoiesis. We show
      that following induced thrombocytopenia, recovery of the peripheral platelet
      count is impaired in PECAM-1-deficient mice. Whereas MK maturation, proplatelet
      formation, and platelet production under in vitro conditions were unaffected, we
      identified a migration defect in PECAM-1-deficient MKs in response to a gradient
      of stromal cell-derived factor 1 (SDF1), a major chemokine regulating MK
      migration within the bone marrow. This defect could be explained by defective
      PECAM-1(-/-) MK polarization of the SDF1 receptor CXCR4 and an increase in
      adhesion to immobilized bone marrow matrix proteins that can be explained by an
      increase in integrin activation. The defect of migration and polarization was
      confirmed in vivo with demonstration of altered spatial localization of MKs
      within the bone marrow in PECAM-1-deficient mice, following immune-induced
      thrombocytopenia. This study identifies a novel role for PECAM-1 in regulating MK
      migration and thrombopoiesis.

PMID- 17234741
TI  - TC-PTP-deficient bone marrow stromal cells fail to support normal B lymphopoiesis
      due to abnormal secretion of interferon-{gamma}.
AB  - The T-cell protein tyrosine phosphatase (TC-PTP) is a negative regulator of the
      Jak/Stat cytokine signaling pathway. Our study shows that the absence of TC-PTP
      leads to an early bone marrow B-cell deficiency characterized by hindered
      transition from the pre-B cell to immature B-cell stage. This phenotype is
      intrinsic to the B cells but most importantly due to bone marrow stroma
      abnormalities. We found that bone marrow stromal cells from TC-PTP(-/-) mice have
      the unique property of secreting 232-890 pg/mL IFN-gamma. These high levels of
      IFN-gamma result in 2-fold reduction in mitotic index on IL-7 stimulation of TC
      PTP(-/-) pre-B cells and lower responsiveness of IL-7 receptor downstream
      Jak/Stat signaling molecules. Moreover, we noted constitutive phosphorylation of
      Stat1 in those pre-B cells and demonstrated that this was due to soluble IFN
      gamma secreted by TC-PTP(-/-) bone marrow stromal cells. Interestingly, culturing
      murine early pre-B leukemic cells within a TC-PTP-deficient bone marrow stroma
      environment leads to a 40% increase in apoptosis in these malignant cells. Our
      results unraveled a new role for TC-PTP in normal B lymphopoiesis and suggest
      that modulation of bone marrow microenvironment is a potential therapeutic
      approach for selected B-cell leukemia.

PMID- 17234742
TI  - Multiple myeloma-reactive T cells recognize an activation-induced minor
      histocompatibility antigen encoded by the ATP-dependent interferon-responsive
      (ADIR) gene.
AB  - Minor histocompatibility antigens (mHags) play an important role in both graft
      versus-tumor effects and graft-versus-host disease (GVHD) after allogeneic stem
      cell transplantation. We applied biochemical techniques and mass spectrometry to
      identify the peptide recognized by a dominant tumor-reactive donor T-cell
      reactivity isolated from a patient with relapsed multiple myeloma who underwent
      transplantation and entered complete remission after donor lymphocyte infusion. A
      frequently occurring single nucleotide polymorphism in the human ATP-dependent
      interferon-responsive (ADIR) gene was found to encode the epitope we designated
      LB-ADIR-1F. Although gene expression could be found in cells from hematopoietic
      as well as nonhematopoietic tissues, the patient suffered from only mild acute
      GVHD despite high percentages of circulating LB-ADIR-1F-specific T cells.
      Differential recognition of nonhematopoietic cell types and resting hematopoietic
      cells as compared with activated B cells, T cells, and tumor cells was
      demonstrated, illustrating variable LB-ADIR-1F expression depending on the
      cellular activation state. In conclusion, the novel mHag LB-ADIR-1F may be a
      suitable target for cellular immunotherapy when applied under controlled
      circumstances.

PMID- 17234743
TI  - Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent
      intestinal IgA production.
AB  - Sphingosine 1-phosphate (S1P) is known to play a pivotal role in the regulation
      of lymphocyte emigration from organized lymphoid tissues such as the peripheral
      lymph nodes and thymus, but its immunologic role in unorganized and diffused
      tissues remains to be elucidated. Here we show that the trafficking of peritoneal
      B cells is principally regulated by S1P. All peritoneal B cells including B1a,
      B1b, and B2 B cells express comparable levels of the type 1 S1P receptor. Thus,
      treatment with FTY720, an S1P receptor modulator, caused the rapid disappearance
      of peritoneal B cells by inhibiting both their emigration from parathymic lymph
      nodes and their recirculation from the blood into the peritoneal cavity without
      affecting their progenitor populations. These changes did not affect natural
      plasma antibody production or phosphorylcholine (PC)-specific antibody production
      in serum after peritoneal immunization with heat-killed Streptococcal pneumoniae
      (R36A). However, FTY720 dramatically reduced peritoneal B cell-derived natural
      intestinal secretory IgA production without affecting the expression of J-chain
      and polyimmunoglobulin receptors. Additionally, FTY720 impaired the generation of
      PC-specific fecal IgA responses after oral immunization with R36A. These findings
      point to a pivotal role for S1P in connecting peritoneal B cells with intestinal
      B-cell immunity.

PMID- 17234744
TI  - Molecular analysis of the methylprednisolone-mediated inhibition of NK-cell
      function: evidence for different susceptibility of IL-2- versus IL-15-activated
      NK cells.
AB  - Steroids have been shown to inhibit the function of fresh or IL-2-activated
      natural killer (NK) cells. Since IL-15 plays a key role in NK-cell development
      and function, we comparatively analyzed the effects of methylprednisolone on IL-2
      or IL-15-cultured NK cells. Methylprednisolone inhibited the surface expression
      of the major activating receptors NKp30 and NKp44 in both conditions, whereas NK
      cell proliferation and survival were sharply impaired only in IL-2-cultured NK
      cells. Accordingly, methylprednisolone inhibited Tyr phosphorylation of STAT1,
      STAT3, and STAT5 in IL-2-cultured NK cells but only marginally in IL-15-cultured
      NK cells, whereas JAK3 was inhibited under both conditions. Also, the NK
      cytotoxicity was similarly impaired in IL-2- or IL-15-cultured NK cells. This
      effect strictly correlated with the inhibition of ERK1/2 Tyr phosphorylation,
      perforin release, and cytotoxicity in a redirected killing assay against the
      FcRgamma(+) P815 target cells upon cross-linking of NKp46, NKG2D, or 2B4
      receptors. In contrast, in the case of CD16, inhibition of ERK1/2 Tyr
      phosphorylation, perforin release, and cytotoxicity were not impaired. Our study
      suggests a different ability of IL-15-cultured NK cells to survive to steroid
      treatment, thus offering interesting clues for a correct NK-cell cytokine
      conditioning in adoptive immunotherapy.

PMID- 17234746
TI  - Evidence for a molecular link between the tuberous sclerosis complex and the
      Crumbs complex.
AB  - In human, mutations in tuberous sclerosis complex protein 1 or 2 (TSC1/2 or
      hamartin/tuberin) cause tuberous sclerosis characterized by the occurrence of
      multiple hamartomas. On the other hand, mutations in the Crumbs homolog-1 (CRB1)
      gene cause retinal degeneration diseases including Leber congenital amaurosis and
      retinitis pigmentosa type 12. Here we report, using a two-hybrid assay, a direct
      molecular interaction between TSC2 C-terminal part and PDZ 2 and 3 of PATJ, a
      scaffold member of the Crumbs 3 (CRB 3) complex in human intestinal epithelial
      cells, Caco2. TSC2 interacts not only with PATJ, but also with the whole CRB 3
      complex by GST-pull down assays. In addition, TSC2 co-immunoprecipitates and co
      localizes partially with PATJ at the level of the tight junctions. Furthermore,
      depletion of PATJ from Caco2 cells induces an increase in mammalian Target Of
      Rapamycin Complex 1 (mTORC1) activity, which is totally inhibited by rapamycin.
      In contrast, in the same cells, inhibition of phosphoinositol-3 kinase (PI-3K) by
      wortmannin does not abolish rpS6 phosphorylation. These functional data indicate
      that the Crumbs complex is a potential regulator of the mTORC1 pathway, cell
      metabolism and survival through a direct interaction with TSC1/2.

PMID- 17234747
TI  - Systemic efficacy with oncolytic virus therapeutics: clinical proof-of-concept
      and future directions.
AB  - Oncolytic viruses that can destroy cancer cells have been engineered in a variety
      of ways with the aim of improving their selectivity and efficacy. Here, we review
      data from clinical investigations of these virotherapeutic agents, specifically
      those that have shown systemic efficacy: vaccinia, measles, mumps, viruses,
      Newcastle disease virus, and reovirus. Further directions for optimizing i.v.
      delivery and efficacy are discussed.

PMID- 17234745
TI  - GATA3 up-regulation associated with surface expression of CD294/CRTH2: a unique
      feature of human Th cells.
AB  - GATA-3 and T-box expressed in T cells (T-bet) play central roles in Th-cell
      development and function. Consistently, studies in mice document their selective
      expression in Th1 and Th2 cells, respectively. In contrast, it is not clear
      whether these genes are regulated in human Th cells. Here we show that T-bet
      expression is polarized to a comparable degree in human and mouse Th-cell
      cultures, while only mouse GATA3 is subject to substantial regulation. This did
      not reflect differential skewing efficiency in human versus mouse cultures, as
      these contained similar frequencies of IFN-gamma- and IL-4-producing cells.
      However, GATA-3 was expressed at significantly higher levels in human IL-4
      producing cells enriched via capture with monoclonal antibodies (mAbs) against
      the PGD(2) receptor, CRTH2, the best selective Th2-cell surface marker to date.
      Along with increased IL-4 and GATA-3, CRTH2(+) Th cells isolated from Th2-skewed
      cultures or the circulating memory pool exhibited markedly decreased IFN-gamma
      and T-bet expression. Thus, the human GATA-3 gene is not regulated in response to
      polarizing signals that are sufficient to direct Th2-specific expression in mouse
      cells. This postulates the involvement of an additional level of complexity in
      the regulation of human GATA-3 expression and stresses the existence of
      nontrivial differences in the regulation of human versus mouse T-cell function.

PMID- 17234748
TI  - Emerging roles of MUC4 in cancer: a novel target for diagnosis and therapy.
AB  - The MUC4 mucin is a transmembrane glycoprotein that is implicated in the
      pathogenesis of pancreatic cancer and is aberrantly expressed in many other
      epithelial carcinomas. Recent studies suggest its significant potential as a
      clinical tool for cancer diagnosis and prognosis. MUC4 modulates HER2/ErbB2
      signaling and is a determinant of therapeutic outcome of Herceptin-based therapy,
      which further indicates its prospective usefulness in cancer therapy and
      treatment planning.

PMID- 17234749
TI  - Angiogenic response caused by oncolytic herpes simplex virus-induced reduced
      thrombospondin expression can be prevented by specific viral mutations or by
      administering a thrombospondin-derived peptide.
AB  - Wild-type (WT) herpes simplex virus (HSV) causes some pathology, such as ocular
      keratitis, by increasing infected tissue vascularity, possibly reflecting altered
      angiogenic factor expression in infected cells. Oncolytic HSVs possess specific
      mutations enabling selective replication in tumor cells. We investigated whether
      this ability to enhance infected tissue vascularity is retained in oncolytic HSV,
      which could be an undesirable effect of oncolytic HSVs that may need to be
      addressed when treating tumors with oncolytic HSVs. s.c. tumors derived from U87
      human glioma cells in athymic mice were treated with oncolytic HSVs G207 or
      G47Delta in the presence or absence of a recombinant protein composed of the
      three type-1 repeats (3TSR) of thrombospondin-1 (TSP-1). Real-time reverse
      transcription-PCR and Western blot of infected cultured cells measured angiogenic
      factor expression. Microvessel density was assessed using immunofluorescence.
      G207-treated U87 s.c. tumors had elevated microvessel densities compared with
      saline- and G47Delta-treated tumors, and G207 treatment caused delayed tumor
      growth resumption. G207-infected U87 and U373 cells exhibited reduced protein,
      not mRNA, expression of angiogenesis inhibitors TSP-1 and thrombospondin-2 (TSP
      2). 3TSR restored the G207-treated tumor microvessel density to the low level of
      G47Delta-treated tumors and prevented delayed growth resumption. Oncolytic HSV
      G207 thus retains the ability of WT HSV to increase infected tissue vascularity.
      In infected tumors, this increased vascularity is mediated by reduced TSP-1 and
      TSP-2 levels and causes delayed tumor growth resumption. Incorporating viral
      mutations, such as those seen in G47Delta or administering thrombospondin-derived
      peptides, counteracts the angiogenic effect of oncolytic HSV and should be
      considered when designing oncolytic HSV therapies.

PMID- 17234750
TI  - Frequent mutation of Apc gene in rat colon tumors and mucin-depleted foci,
      preneoplastic lesions in experimental colon carcinogenesis.
AB  - Mucin-depleted foci (MDF) are microscopic dysplastic lesions induced in the colon
      of rodents by specific colon carcinogens. Most MDF show Wnt pathway activation,
      whereas only a subset shows mutations in the Ctnnb1 gene, coding for beta
      catenin. Because Apc is a member of the Wnt pathway and the most frequent mutated
      gene in human colon cancer, we tested whether MDF harbor Apc mutations. F344 rats
      were treated twice with 150 mg/kg of 1,2-dimethylhydrazine. After 15 or 28 weeks,
      MDF, aberrant crypt foci (ACF), and tumors were collected. We screened a segment
      of the Apc gene comprising the region homologous to the mutation cluster region
      (MCR) of human APC, which frequently shows mutations in experimental colon
      tumors. Mutations were identified by PCR amplification and sequencing in 6:24 MDF
      (25%), 7:23 tumors (30%), 0:24 ACF (0%). Most of the mutations (92%) in MDF and
      tumors were localized in a region upstream from the MCR. All mutations were
      single-base substitutions and mainly formed by G:C-->A:T and C:G-->T:A
      transitions. The pattern of nucleotide changes was similar in MDF and tumors,
      and, interestingly, the same mutation in codon 1047 was found in two MDF and in
      three tumors. Four out of the six mutations found in MDF were nonsense mutations,
      and two were missense. All mutations in tumors determined a protein truncation.
      These results show that Apc mutations are present in MDF with a frequency similar
      to that of tumors, strengthening the evidence that they are precancerous lesions
      in colon carcinogenesis.

PMID- 17234751
TI  - Nutlin3 blocks vascular endothelial growth factor induction by preventing the
      interaction between hypoxia inducible factor 1alpha and Hdm2.
AB  - Hdm2 is elevated in numerous types of malignancies and is thought to impede the
      function of wild-type p53. Reactivation of p53 by disrupting the association with
      Hdm2 was the impetus for the development of Nutlin3. Although regulation of p53
      has been the central focus of Hdm2 activity, it also binds other proteins through
      its p53-binding domain. Here, we show that hypoxia-inducible factor 1alpha
      (HIF1alpha) binds to Hdm2 in the domain designated to bind p53. HIF1alpha and p53
      share a conserved motif that is required to bind Hdm2. Distinct complexes form
      between Hdm2-HIF1alpha and Hdm2-p53 as determined by immunoprecipitation of
      nuclear extracts and in vitro. The Hdm2 antagonist Nutlin3 prevents the
      association between Hdm2 and HIF1alpha. The vascular endothelial growth factor
      (VEGF) gene is a transcriptional target of HIF1alpha, and under normoxic or
      hypoxic conditions, Hdm2 increases HIF1alpha activity to induce VEGF production.
      Blocking the association of Hdm2 and HIF1alpha by Nutlin3, or ablating Hdm2
      expression, diminished the level of VEGF under conditions of normoxia or hypoxia.
      Our findings establish a unique role for Nutlin3 in attenuating VEGF induction by
      preventing the association of Hdm2 with HIF1alpha.

PMID- 17234752
TI  - NKX3.1 homeodomain protein binds to topoisomerase I and enhances its activity.
AB  - The prostate-specific homeodomain protein NKX3.1 is a tumor suppressor that is
      commonly down-regulated in human prostate cancer. Using an NKX3.1 affinity
      column, we isolated topoisomerase I (Topo I) from a PC-3 prostate cancer cell
      extract. Topo I is a class 1B DNA-resolving enzyme that is ubiquitously expressed
      in higher organisms and many prokaryotes. NKX3.1 interacts with Topo I to enhance
      formation of the Topo I-DNA complex and to increase Topo I cleavage of DNA. The
      two proteins interacted in affinity pull-down experiments in the presence of
      either DNase or RNase. The NKX3.1 homeodomain was essential, but not sufficient,
      for the interaction with Topo I. NKX3.1 binding to Topo I occurred independently
      of the Topo I NH2-terminal domain. The binding of equimolar amounts of Topo I to
      NKX3.1 caused displacement of NKX3.1 from its cognate DNA recognition sequence.
      Topo I activity in prostates of Nkx3.1+/- and Nkx3.1-/- mice was reduced compared
      with wild-type mice, whereas Topo I activity in livers, where no NKX3.1 is
      expressed, was independent of Nkx3.1 genotype. Endogenous Topo I and NKX3.1 could
      be coimmunoprecipitated from LNCaP cells, where NKX3.1 and Topo I were found to
      colocalize in the nucleus and comigrate within the nucleus in response to either
      gamma-irradiation or mitomycin C exposure, two DNA-damaging agents. This is the
      first report that a homeodomain protein can modify the activity of Topo I and may
      have implications for organ-specific DNA replication, transcription, or DNA
      repair.

PMID- 17234753
TI  - Distinguishing cancer-associated missense mutations from common polymorphisms.
AB  - Missense variants are commonly identified in genomic sequence but only a small
      fraction directly contribute to oncogenesis. The ability to distinguish those
      missense changes that contribute to cancer progression from those that do not is
      a difficult problem usually only accomplished through functional in vivo
      analyses. Using two computational algorithms, Sorting Intolerant from Tolerant
      (SIFT) and the Pfam-based LogR.E-value method, we have identified features that
      distinguish cancer-associated missense mutations from other classes of missense
      change. Our data reveal that cancer mutants behave similarly to Mendelian disease
      mutations, but are clearly distinct from either complex disease mutations or
      common single-nucleotide polymorphisms. We show that both activating and
      inactivating oncogenic mutations are predicted to be deleterious, although
      activating changes are likely to increase protein activity. Using the Gene
      Ontology and data from the SIFT and LogR.E-value metrics, a classifier was built
      that predicts cancer-associated missense mutations with a very low false-positive
      rate. The classifier does remarkably well in a number of different experiments
      designed to distinguish polymorphisms from true cancer-associated mutations. We
      also show that recurrently observed mutations are much more likely to be
      predicted to be cancer-associated than rare mutations, suggesting that our
      classifier will be useful in distinguishing causal from passenger mutations. In
      addition, from an expressed sequence tag-based screen, we identified a previously
      unknown germ line change (P1104A) in tumor tissues that is predicted to disrupt
      the function of the TYK2 protein. The data presented here show that this novel
      bioinformatics approach to classifying cancer-associated variants is robust and
      can be used for large-scale analyses.

PMID- 17234754
TI  - IFN-alpha-stimulated genes and Epstein-Barr virus gene expression distinguish WHO
      type II and III nasopharyngeal carcinomas.
AB  - Nonkeratinizing nasopharyngeal carcinoma (NPC) is 100% associated with Epstein
      Barr Virus (EBV) and divided into two subtypes (WHO types II and III) based on
      histology. We tested whether these subtypes can be distinguished at the molecular
      genetic level using an algorithm that analyzes sets of related genes (gene set
      enrichment analysis). We found that a class of IFN-stimulated genes (ISG),
      frequently associated with the antiviral response, was significantly activated in
      type III versus type II NPC. Consistent with this, replication of the endogenous
      EBV was suppressed in type III. A strong association was also seen with a subset
      of ISGs previously identified in systemic lupus erythematosus, another disease in
      which 'normal' EBV biology is deregulated, suggesting that this pattern of ISG
      expression may be linked to the increased EBV activity in both diseases. In
      contrast, unsupervised hierarchical clustering of the complete expression
      profiles failed to distinguish the two subsets. These results suggest that type
      II and III NPC have not originated from obviously distinct epithelial precursors;
      rather, the histologic differences may be a consequence of a differential
      antiviral response, involving IFNs, to chronic EBV infection.

PMID- 17234755
TI  - Drosophila split ends homologue SHARP functions as a positive regulator of
      Wnt/beta-catenin/T-cell factor signaling in neoplastic transformation.
AB  - Wnt ligands have pleiotropic and context-specific roles in embryogenesis and
      adult tissues. Among other effects, certain Wnts stabilize the beta-catenin
      protein, leading to the ability of beta-catenin to activate T-cell factor (TCF)
      mediated transcription. Mutations resulting in constitutive beta-catenin
      stabilization underlie development of several human cancers. Genetic studies in
      Drosophila highlighted the split ends (spen) gene as a positive regulator of Wnt
      dependent signaling. We have assessed the role of SHARP, a human homologue of
      spen, in Wnt/beta-catenin/TCF function in mammalian cells. We found that SHARP
      gene and protein expression is elevated in human colon and ovarian endometrioid
      adenocarcinomas and mouse colon adenomas and carcinomas carrying gene defects
      leading to beta-catenin dysregulation. When ectopically expressed, the silencing
      mediator for retinoid and thyroid receptors/histone deacetylase 1-associated
      repressor protein (SHARP) protein potently enhanced beta-catenin/TCF
      transcription of a model reporter gene and cellular target genes. Inhibition of
      endogenous SHARP function via RNA inhibitory (RNAi) approaches antagonized beta
      catenin/TCF-mediated activation of target genes. The effect of SHARP on beta
      catenin/TCF-regulated genes was mediated via a functional interaction between
      SHARP and TCF. beta-Catenin-dependent neoplastic transformation of RK3E cells was
      enhanced by ectopic expression of SHARP, and RNAi-mediated inhibition of
      endogenous SHARP in colon cancer cells inhibited their transformed growth. In
      toto, our findings implicate SHARP as an important positive regulator of Wnt
      signaling in cancers with beta-catenin dysregulation.

PMID- 17234756
TI  - Depletion of the Ras association domain family 1, isoform A-associated novel
      microtubule-associated protein, C19ORF5/MAP1S, causes mitotic abnormalities.
AB  - Ras association domain family 1, isoform A (RASSF1A) is a novel tumor suppressor
      gene that is found to be inactivated in more than 40 types of sporadic cancers.
      In addition, mouse Rassf1a knockout models have an increased frequency of
      spontaneous and induced tumors. The mechanisms by which RASSF1A exerts its tumor
      suppression activities or the pathways it can regulate are not yet fully
      understood. Using yeast two-hybrid system, we have previously identified
      C19ORF5/MAP1S as the major RASSF1A-interacting protein. C19ORF5 has two conserved
      microtubule-associated regions and may function to anchor RASSF1A to the
      centrosomes. In this study, we have analyzed the cellular functions of C19ORF5.
      By using small interfering RNA-mediated depletion and time-lapse video
      microscopy, we show that C19ORF5 knockdown causes mitotic abnormalities that
      consist of failure to form a stable metaphase plate, premature sister chromatid
      separation, lagging chromosomes, and multipolar spindles. We also show that a
      fraction of C19ORF5 localizes to the spindle microtubules. Additionally, we show
      here that C19ORF5 localizes to the microtubule-organizing centers during
      microtubule regrowth after nocodazole washout. Knockdown of C19ORF5 disrupts the
      microtubule-organizing center and results in microtubule nucleation from several
      sites. Whereas the localization of pericentrin is not affected, alpha- and gamma
      tubulin localization and sites of nucleation are greatly altered by C19ORF5
      depletion. This may indicate that C19ORF5 plays a role in anchoring the
      microtubule-organizing center to the centrosomes. In addition, we show that the
      NH2 terminus of C19ORF5 is essential for this process. This novel role for
      C19ORF5 could explain the resulting mitotic abnormalities that occur on its
      depletion and can potentially provide an underlying mechanism for the frequent
      centrosome and microtubule abnormalities detected in several cancers.

PMID- 17234757
TI  - Nestin is expressed in the basal/myoepithelial layer of the mammary gland and is
      a selective marker of basal epithelial breast tumors.
AB  - Transcriptional profiling has identified five breast cancer subtypes, of which
      the basal epithelial is most aggressive and correlates with poor prognosis. These
      tumors display a high degree of cellular heterogeneity and lack established
      molecular targets, such as estrogen receptor-alpha, progesterone receptor, and
      Her2 overexpression, indicating a need for definitive diagnostic markers. We
      present evidence that nestin, a previously described marker of regenerative cells
      in diverse tissues, is expressed in the regenerative compartment of the normal
      human mammary gland. Colocalization studies indicate two distinct populations of
      mammary epithelia that express nestin: one expressing cytokeratin 14 (CK14) and
      DeltaN-p63 and another expressing desmin. Immunohistochemical analysis indicates
      that DeltaN-p63 and nestin are coordinately expressed during pregnancy in the
      murine mammary gland. In the embryonal carcinoma cell line NT2/D1, ectopic DeltaN
      p63-alpha disrupts retinoic acid-induced differentiation, thereby preserving
      expression of nestin; however, small interfering RNA-mediated ablation of nestin
      is insufficient to promote differentiation, indicating that whereas nestin may
      identify cells within the regenerative compartment of the mammary gland, it is
      insufficient to block differentiation and preserve replicative capacity.
      Immunohistochemical analysis of basal epithelial breast tumors, including those
      shown to carry BRCA1 mutations, indicates robust expression of nestin and CK14,
      punctate expression of p63, and low to undetectable levels of desmin expression.
      Nestin was not detected in other breast cancer subtypes, indicating selectivity
      for basal epithelial breast tumors. These studies identify nestin as a selective
      marker of the basal breast cancer phenotype, which displays features of mammary
      progenitors.

PMID- 17234758
TI  - Stromal-epithelial cell interactions and androgen receptor-coregulator
      recruitment is altered in the tissue microenvironment of prostate cancer.
AB  - Tissue recombination experiments show that prostate mesenchyma directs prostate
      epithelial cell growth and development in an androgen-dependent manner, and that
      functional differentiation of prostate epithelium requires androgen-driven
      processes in both epithelia and stroma. The androgen induction of target genes in
      primary cultures of prostate stromal and epithelial cells was determined using an
      adenoviral expression system, which employed the MMTV-enhancer driven luciferase
      reporter as an androgen receptor (AR)-mediated transcription assay. These studies
      indicate that both cell types contain functional AR. Androgen induction of
      luciferase reporter activity is 3-fold in stromal cells compared with 10-fold in
      epithelial cells. AR-mediated transcription activity in stroma cells was enhanced
      by coculture with epithelial cells or epithelial cell-conditioned media. The
      elevated AR-mediated transcription activity in stromal cells that were exposed to
      epithelial factors correlated with increased recruitment of coactivators to the
      AR transcriptional complex. Epithelial cells facilitated interactions of AR with
      SRC-1 in an androgen-dependent manner. However, AR-mediated transcriptional
      activity in stromal cells isolated from prostate cancer was reduced compared with
      stromal cells isolated from benign prostate and continued to be reduced when
      cocultured with tumor-derived prostate epithelial cells. The occupancy of AR and
      coregulators on target genes showed that androgen-bound AR in prostate cancer
      stromal cells was associated with the corepressor silencing mediator for retinoid
      and thyroid hormone receptor. Thus, the ability of epithelial cells to modulate
      coregulator recruitment to the AR transcriptional complex on androgen-responsive
      genes seems altered in the stromal microenvironment of prostate cancer.

PMID- 17234759
TI  - Merlin/neurofibromatosis type 2 suppresses growth by inhibiting the activation of
      Ras and Rac.
AB  - The small G-protein Ras is a tightly controlled regulator of cell fate. Prolonged
      or persistent arrest in the activated GTP-loaded state by mutation of Ras as in
      lung cancer or in a Ras-GTPase-activating protein as in neurofibromatosis type 1
      promotes tumorigenesis. We now show that the tumor-suppressor protein merlin
      (mutated in neurofibromatosis type 2) also controls Ras activity. Systematic
      analysis of growth factor signaling located the step of merlin interference to
      the activation of Ras and Rac. Merlin independently uncouples both Ras and Rac
      from growth factor signals. In the case of Ras, merlin acts downstream of the
      receptor tyrosine kinase-growth factor receptor binding protein 2 (Grb2)-SOS
      complex. However, merlin does not bind either SOS or Ras, but it counteracts the
      ERM (ezrin, radixin, moesin)-dependent activation of Ras, which correlates with
      the formation of a complex comprising ERM proteins, Grb2, SOS, Ras, and
      filamentous actin. Because efficient signaling from Ras requires Rac-p21
      activated kinase-dependent phosphorylations of Raf and mitogen-activated
      protein/extracellular signal-regulated kinase kinase, merlin can also inhibit
      signal transfer from dominantly active Ras mutants. We propose that the
      interference of merlin with Ras- and Rac-dependent signal transfer represents
      part of the tumor-suppressive action of merlin.

PMID- 17234760
TI  - SOX9 is expressed in normal prostate basal cells and regulates androgen receptor
      expression in prostate cancer cells.
AB  - SOX9 is a member of the SOX [Sry-related high-mobility group (HMG) box] family of
      HMG DNA-binding domain transcription factors and is required for the development
      and differentiation of multiple cell lineages. This report shows that basal
      epithelial cells express SOX9 in normal prostate, with no detectable expression
      in luminal epithelial cells. In contrast, SOX9 is expressed in primary prostate
      cancers in vivo, at a higher frequency in recurrent prostate cancer and in
      prostate cancer cell lines (LNCaP, CWR22, PC3, and DU145). SOX9 message and
      protein levels in prostate cancer cells were increased by treatment with glycogen
      synthase kinase 3beta inhibitor (SB415286), and SOX9 was reduced when beta
      catenin was down-regulated by small interfering RNA (siRNA), indicating that SOX9
      expression in prostate cancer is regulated by Wnt/beta-catenin signaling. SOX9
      bound specifically to androgen receptor (AR) DNA-binding domain glutathione S
      transferase fusion proteins, and this interaction was dependent on a short
      peptide immediately COOH-terminal to the DNA-binding domain (the C-terminal
      extension), which is required for interactions between steroid hormone receptors
      and the architectural HMG proteins. Exogenous SOX9 expressed at high
      nonphysiologic levels decreased AR expression and activity; however, at lower
      levels, SOX9 increased AR protein expression. Significantly, down-regulation of
      SOX9 by siRNA in prostate cancer cells reduced endogenous AR protein levels, and
      cell growth indicating that SOX9 contributes to AR regulation and decreased
      cellular proliferation. These results indicate that SOX9 in prostate basal cells
      supports the development and maintenance of the luminal epithelium and that a
      subset of prostate cancer cells may escape basal cell requirements through SOX9
      expression.

PMID- 17234761
TI  - RUNX1 DNA-binding mutants, associated with minimally differentiated acute
      myelogenous leukemia, disrupt myeloid differentiation.
AB  - Mutations in the RUNX1 gene are found at high frequencies in minimally
      differentiated acute myelogenous leukemia. In addition to null mutations, many of
      the mutations generate Runx1 DNA-binding (RDB) mutants. To determine if these
      mutants antagonize wild-type protein activity, cDNAs were transduced into murine
      bone marrow or human cord blood cells using retroviral vectors. Significantly,
      the RDB mutants did not act in a transdominant fashion in vivo to disrupt Runx1
      activity in either T-cell or platelet development, which are highly sensitive to
      Runx1 dosage. However, RDB mutant expression impaired expansion and
      differentiation of the erythroid compartment in which Runx1 expression is
      normally down-regulated, showing that a RDB-independent function is incompatible
      with erythroid differentiation. Significantly, both bone marrow progenitors
      expressing RDB mutants or deficient for Runx1 showed increased replating
      efficiencies in vitro, accompanied by the accumulation of myeloblasts and
      dysplastic progenitors, but the effect was more pronounced in RDB cultures.
      Disruption of the interface that binds CBFbeta, an important cofactor of Runx1,
      did not impair RDB mutant replating activity, arguing against inactivation of
      Runx1 function by CBFbeta sequestration. We propose that RDB mutants antagonize
      Runx1 function in early progenitors by disrupting a critical balance between DNA
      binding-independent and DNA-binding-dependent signaling.

PMID- 17234762
TI  - Human prx1 gene is a target of Nrf2 and is up-regulated by hypoxia/reoxygenation:
      implication to tumor biology.
AB  - Peroxiredoxin 1 (Prx1) has been found to be elevated in several human cancers.
      The cell survival-enhancing function of Prx1 is traditionally attributed to its
      reactive oxygen species-removing capacity, although the growth-promoting role of
      Prx1 independent of this antioxidant activity is increasingly gaining attention.
      Although much progress has been made in understanding the behavior of Prx1,
      little information is available on the mechanism responsible for the abnormal
      elevation of Prx1 level in cancer. We hypothesized that the hypoxic and unstable
      oxygenation microenvironment of a tumor might be crucial for prx1 up-regulation.
      In this study, we cloned the human prx1 promoter and identified nuclear factor
      (erythroid-derived 2)-related factor 2 (Nrf2) as a key transcription factor.
      Hypoxia/reoxygenation, an in vitro condition suited to mimic changes of
      oxygenation, increased Nrf2 nuclear localization and its binding to the
      electrophile-responsive elements located at the proximal (-536 to -528) and
      distal (-1429 to -1421) regions of the prx1 promoter. A significant reduction of
      both steady-state and hypoxia/reoxygenation-mediated prx1 gene expression was
      shown in Nrf2 knock-out cells. Our results indicated that decreased Kelch-like
      ECH-associated protein, Keap1, might be an important mechanism for the increased
      nuclear translocation and activation of Nrf2 in response to
      hypoxia/reoxygenation. A constitutive elevation of prx1 mRNA and protein was
      observed in Keap1 knock-out cells. The above information suggests that the Nrf2
      Prx1 axis may be a fruitful target for intervention with respect to inhibiting
      the malignant progression and/or reducing the treatment resistance of cancer
      cells.

PMID- 17234763
TI  - Human bone marrow activates the Akt pathway in metastatic prostate cells through
      transactivation of the alpha-platelet-derived growth factor receptor.
AB  - The factors regulating the bone tropism of disseminated prostate cancer cells are
      still vaguely defined. We report that prostate cancer cells that metastasize to
      the skeleton respond to human bone marrow with a robust stimulation of the
      phosphatidylinositol 3-kinase/Akt pathway, whereas prostate cells that lack bone
      metastatic potential respond negligibly. The majority of this Akt activation is
      dependent on alpha-platelet-derived growth factor receptor (alpha-PDGFR)
      signaling, which was shown using the small-molecule inhibitor of PDGFR signaling
      AG1296. Low concentrations of PDGF-AA and PDGF-BB found in bone marrow aspirates,
      which were detected by ELISA, do not account for the high levels of alpha-PDGFR
      signaling. Additionally, neutralizing PDGF binding using a alpha-PDGFR-specific
      antibody (IMC-3G3) failed to produce a significant inhibition of bone marrow
      induced Akt activation. However, the inhibitory effect of IMC-3G3 rivaled that of
      AG1296 when incubation was done under conditions that stimulated alpha-PDGFR
      internalization. We conclude that alpha-PDGFR is activated by multiple soluble
      factors contained within human bone marrow, in addition to its natural ligands,
      and this transactivation is dependent on receptor localization to the plasma
      membrane. Therefore, alpha-PDGFR expression may provide select prostate
      phenotypes with a growth advantage within the bone microenvironment.

PMID- 17234764
TI  - Hypoxia-inducible factor-1alpha is a key regulator of metastasis in a transgenic
      model of cancer initiation and progression.
AB  - Adaptation to hypoxia is a critical step in tumor progression and is, in part,
      regulated by the transcription factor hypoxia-inducible factor-1alpha (HIF
      1alpha). Xenograft models have been extensively used to characterize the role of
      HIF-1alpha in experimental cancers. Although these models provide an
      understanding of tumor growth at terminal stages of malignancy, they do not
      address tumor initiation or metastatic progression. To elucidate these roles, HIF
      1alpha was conditionally deleted in the mammary epithelium of a transgenic mouse
      model for metastatic breast cancer. Conditional deletion of HIF-1alpha in the
      mammary epithelium resulted in delayed tumor onset and retarded tumor growth;
      this was correlated with decreased tumor cell proliferation. Tumors with
      conditional deletion of HIF-1alpha were also less vascular during early tumor
      progression. Perhaps most surprisingly, deletion of HIF-1alpha in the mammary
      epithelium resulted in decreased pulmonary metastasis. These results show that
      whereas HIF-1alpha is not required for the initiation of breast tumor growth or
      tumor cell metastasis, the transcriptional activity of HIF-1alpha is a
      significant positive regulator of tumor progression and metastatic potential.

PMID- 17234766
TI  - O6-methylguanine-DNA methyltransferase regulation by p53 in astrocytic cells.
AB  - Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter
      (i.e., gene silencing) occurs in 40% to 50% of patients with glioblastoma and
      predicts benefit from temozolomide chemotherapy; when unmethylated, MGMT repairs
      DNA damage induced by temozolomide, contributing to chemoresistance. In this
      study, we tested the hypothesis that MGMT is regulated by p53 in astrocytic
      cells, the precursors of which may give rise to glioblastoma. p53 is of interest
      because, in addition to often being mutated in glioblastoma, inactivation
      sensitizes some astrocytoma cell lines to temozolomide. MGMT expression was
      examined in neonatal murine astrocytes and SF767 human astrocytic glioma cells
      following p53 inactivation by knockout (murine only) or RNAi methods. MGMT mRNA
      and protein were detected in murine wild-type p53 astrocytes. However, in
      knockout murine astrocytes and wild-type cells in which p53 was inhibited by
      RNAi, MGMT expression was reduced by >90%. This effect of p53 on MGMT expression
      was unrelated to MGMT promoter methylation-in both wild-type and p53-null
      astrocytes, the MGMT promoter was unmethylated. In wild-type astrocytes, the p53
      protein localized to a regulatory region of the MGMT promoter. In SF767 human
      astrocytic glioma cells, transient knockdown of p53 led to the down-regulation of
      MGMT gene expression. In murine astrocytes and SF767 cells, p53 regulates MGMT
      expression without affecting promoter methylation; in astrocytes, this effect may
      be due to direct binding of p53 to the MGMT promoter. These results imply that
      the best use of temozolomide requires a thorough understanding of MGMT
      regulation.

PMID- 17234765
TI  - An antagonist of dishevelled protein-protein interaction suppresses beta-catenin
      dependent tumor cell growth.
AB  - Recent progress in the development of inhibitors of protein-protein interactions
      has opened the door for developing drugs that act by novel and selective
      mechanisms. Building on that work, we designed a small-molecule inhibitor of the
      Wnt signaling pathway, which is aberrantly activated across a wide range of human
      tumors. The compound, named FJ9, disrupts the interaction between the Frizzed-7
      Wnt receptor and the PDZ domain of Dishevelled, down-regulating canonical Wnt
      signaling and suppressing tumor cell growth. The antitumorigenic effects of FJ9
      were pronounced, including induction of apoptosis in human cancer cell lines and
      tumor growth inhibition in a mouse xenograft model. FJ9 is thus among the first
      non-peptide inhibitors to show therapeutic efficacy through disruption of PDZ
      protein-protein interactions.

PMID- 17234768
TI  - Vascular endothelial growth factor receptor 3 is involved in tumor angiogenesis
      and growth.
AB  - Vascular endothelial growth factor receptor 3 (VEGFR-3) binds VEGF-C and VEGF-D
      and is essential for the development of the lymphatic vasculature. Experimental
      tumors that overexpress VEGFR-3 ligands induce lymphatic vessel sprouting and
      enlargement and show enhanced metastasis to regional lymph nodes and beyond,
      whereas a soluble form of VEGFR-3 that blocks receptor signaling inhibits these
      changes and metastasis. Because VEGFR-3 is also essential for the early blood
      vessel development in embryos and is up-regulated in tumor angiogenesis, we
      wanted to determine if an antibody targeting the receptor that interferes with
      VEGFR-3 ligand binding can inhibit primary tumor growth. Our results show that
      antibody interference with VEGFR-3 function can inhibit the growth of several
      human tumor xenografts in immunocompromised mice. Immunohistochemical analysis
      showed that the blood vessel density of anti-VEGFR-3-treated tumors was
      significantly decreased and hypoxic and necrotic tumor tissue was increased when
      compared with tumors treated with control antibody, indicating that blocking of
      the VEGFR-3 pathway inhibits angiogenesis in these tumors. As expected, the anti
      VEGFR-3-treated tumors also lacked lymphatic vessels. These results suggest that
      the VEGFR-3 pathway contributes to tumor angiogenesis and that effective
      inhibition of tumor progression may require the inhibition of multiple angiogenic
      targets.

PMID- 17234769
TI  - Gene expression profiling of childhood adrenocortical tumors.
AB  - Pediatric adrenocortical tumors (ACT) are rare and often fatal malignancies;
      little is known regarding their etiology and biology. To provide additional
      insight into the nature of ACT, we determined the gene expression profiles of 24
      pediatric tumors (five adenomas, 18 carcinomas, and one undetermined) and seven
      normal adrenal glands. Distinct patterns of gene expression, validated by
      quantitative real-time PCR and Western blot analysis, were identified that
      distinguish normal adrenal cortex from tumor. Differences in gene expression were
      also identified between adrenocortical adenomas and carcinomas. In addition,
      pediatric adrenocortical carcinomas were found to share similar patterns of gene
      expression when compared with those published for adult ACT. This study
      represents the first microarray analysis of childhood ACT. Our findings lay the
      groundwork for establishing gene expression profiles that may aid in the
      diagnosis and prognosis of pediatric ACT, and in the identification of signaling
      pathways that contribute to this disease.

PMID- 17234767
TI  - The inflammatory cytokine tumor necrosis factor-alpha generates an autocrine
      tumor-promoting network in epithelial ovarian cancer cells.
AB  - Constitutive expression of the inflammatory cytokine tumor necrosis factor-alpha
      (TNF-alpha) is characteristic of malignant ovarian surface epithelium. We
      investigated the hypothesis that this autocrine action of TNF-alpha generates and
      sustains a network of other mediators that promote peritoneal cancer growth and
      spread. When compared with two ovarian cancer cell lines that did not make TNF
      alpha, constitutive production of TNF-alpha was associated with greater release
      of the chemokines CCL2 and CXCL12, the cytokines interleukin-6 (IL-6) and
      macrophage migration-inhibitory factor (MIF), and the angiogenic factor vascular
      endothelial growth factor (VEGF). TNF-alpha production was associated also with
      increased peritoneal dissemination when the ovarian cancer cells were
      xenografted. We next used RNA interference to generate stable knockdown of TNF
      alpha in ovarian cancer cells. Production of CCL2, CXCL12, VEGF, IL-6, and MIF
      was decreased significantly in these cells compared with wild-type or mock
      transfected cells, but in vitro growth rates were unaltered. Tumor growth and
      dissemination in vivo were significantly reduced when stable knockdown of TNF
      alpha was achieved. Tumors derived from TNF-alpha knockdown cells were
      noninvasive and well circumscribed and showed high levels of apoptosis, even in
      the smallest deposits. This was reflected in reduced vascularization of TNF-alpha
      knockdown tumors. Furthermore, culture supernatants from such cells failed to
      stimulate endothelial cell growth in vitro. We conclude that autocrine production
      of TNF-alpha by ovarian cancer cells stimulates a constitutive network of other
      cytokines, angiogenic factors, and chemokines that may act in an
      autocrine/paracrine manner to promote colonization of the peritoneum and
      neovascularization of developing tumor deposits.

PMID- 17234770
TI  - Suppression of mammary carcinoma cell growth by retinoic acid: the cell cycle
      control gene Btg2 is a direct target for retinoic acid receptor signaling.
AB  - The anticarcinogenic activities of retinoic acid (RA) are believed to be mediated
      by the nuclear RA receptor (RAR) and by the RA-binding protein cellular RA
      binding protein-II (CRABP-II). In MCF-7 mammary carcinoma cells, growth
      inhibition by RA entails an early cell cycle arrest followed by induction of
      apoptosis. Here, we aimed to obtain insights into the initial cell cycle
      response. We show that a 3- to 5-h RA pulse is sufficient for inducing a robust
      growth arrest 2 to 4 days later, demonstrating inhibition of the G1-S transition
      by RA is triggered by immediate-early RAR targets and does not require the
      continuous presence of the hormone throughout the arrest program. Expression
      array analyses revealed that RA induces the expression of several genes involved
      in cell cycle regulation, including the p53-controlled antiproliferative gene B
      cell translocation gene, member 2 (Btg2) and the BTG family member Tob1. We show
      that induction of Btg2 by RA does not require de novo protein synthesis and is
      augmented by overexpression of CRABP-II. Additionally, we identify a RA response
      element in the Btg2 promoter and show that the element binds retinoid X
      receptor/RAR heterodimers in vitro, is occupied by the heterodimers in cells, and
      can drive RA-induced activation of a reporter gene. Hence, Btg2 is a novel direct
      target for RA signaling. In concert with the reports that Btg2 inhibits cell
      cycle progression by down-regulating cyclin D1, induction of Btg2 by RA was
      accompanied by a marked decrease in cyclin D1 expression. The observations thus
      show that the antiproliferative activity of RA in MCF-7 cells is mediated, at
      least in part, by Btg2.

PMID- 17234771
TI  - Heat shock protein 70 increases tumorigenicity and inhibits apoptosis in
      pancreatic adenocarcinoma.
AB  - Pancreatic carcinoma is a malignant disease that responds poorly to chemotherapy
      because of its resistance to apoptosis. Heat shock proteins (Hsp) are not only
      cytoprotective but also interfere with the apoptotic cascade. Here, we
      investigated the role of Hsp70 in regulating apoptosis in pancreatic cancer
      cells. Hsp70 expression was increased in pancreatic cancer cells compared with
      normal pancreatic ductal cells. This was confirmed by increased mRNA levels for
      Hsp70 in human pancreatic cancer tissue compared with neighboring normal tissue
      from the same patient. Depletion of Hsp70 by quercetin decreased cell viability
      and induced apoptosis in cancer cells but not in normal pancreatic ductal cells.
      To show that this is a specific effect of Hsp70 on apoptosis, levels of Hsp70
      were knocked down by short interfering RNA treatment, which also induced
      apoptosis in cancer cells as indicated by Annexin V staining and caspase
      activation. Daily administration of quercetin to nude mice decreased tumor size
      as well as Hsp70 levels in tumor tissue. These findings indicate that Hsp70 plays
      an important role in apoptosis and that selective Hsp70 knockdown can be used to
      induce apoptosis in pancreatic cancer cells.

PMID- 17234772
TI  - Synuclein-gamma targeting peptide inhibitor that enhances sensitivity of breast
      cancer cells to antimicrotubule drugs.
AB  - Synuclein-gamma (SNCG) plays oncogenic roles in breast carcinogenesis. Although
      the expression of SNCG is abnormally high in advanced and metastatic breast
      carcinomas, SNCG is not expressed in normal or benign breast tissues. SNCG is an
      intrinsically disordered protein known to interact with BubR1, a mitotic
      checkpoint kinase. The SNCG-BubR1 interaction inhibits mitotic checkpoint control
      upon spindle damage caused by anticancer drugs, such as nocodazole and taxol.
      Antimicrotubule drugs that cause mitotic arrest and subsequent apoptosis of
      cancer cells are frequently used to treat breast cancer patients with advanced or
      metastatic diseases. However, patient response rates to this class of
      chemotherapeutic agents vary significantly. In this study, we have designed a
      novel peptide (ANK) and shown its interaction with SNCG using fluorometry,
      surface plasmon resonance, and isothermal titration calorimetry. Binding of the
      ANK peptide did not induce folding of SNCG, suggesting that SNCG can function
      biologically in its intrinsically disordered state. Microinjection of the ANK
      peptide in breast cancer cell line overexpressing SNCG (MCF7-SNCG) exhibited a
      similar cell killing response by nocodazole as in the SNCG-negative MCF7 cells.
      Overexpression of enhanced green fluorescent protein-tagged ANK reduces SNCG
      mediated resistance to paclitaxel treatment by approximately 3.5-fold. Our
      coimmunoprecipitation and colocalization results confirmed the intracellular
      association of the ANK peptide with SNCG. This is likely due to the disruption of
      the interaction of SNCG with BubR1 interaction. Our findings shed light on the
      molecular mechanism of the ANK peptide in releasing SNCG-mediated drug
      resistance.

PMID- 17234773
TI  - Adenovirus-mediated expression of a dominant negative Ku70 fragment
      radiosensitizes human tumor cells under aerobic and hypoxic conditions.
AB  - Ku70 is one component of a protein complex, the Ku70/Ku80 heterodimer, which
      binds to DNA double-strand breaks and activates DNA-dependent protein kinase (DNA
      PK), leading to DNA damage repair. Our previous work has confirmed that Ku70 is
      important for DNA damage repair in that Ku70 deficiency compromises the ability
      of cells to repair DNA double-strand breaks, increases the radiosensitivity of
      cells, and enhances radiation-induced apoptosis. Because of the radioresistance
      of some human cancers, particularly glioblastoma, we examined the use of a radio
      gene therapy paradigm to sensitize cells to ionizing radiation. Based on the
      analysis of the structure-function of Ku70 and the crystal structure of Ku70/Ku80
      heterodimer, we designed and identified a candidate dominant negative fragment
      involving an NH(2)-terminal deletion, and designated it as DNKu70. We generated
      this mutant construct, stably overexpressed it in Rat-1 cells, and showed that it
      has a dominant negative effect (i.e., DNKu70 overexpression results in decreased
      Ku-DNA end-binding activity, and increases radiosensitivity). We then constructed
      and generated recombinant replication-defective adenovirus, with DNKu70
      controlled by the cytomegalovirus promoter, and infected human glioma U-87 MG
      cells and human colorectal tumor HCT-8 cells. We show that the infected cells
      significantly express DNKu70 and are greatly radiosensitized under both aerobic
      and hypoxic conditions. The functional ramification of DNKu70 was further shown
      in vivo: expression of DNKu70 inhibits radiation-induced DNA-PK catalytic subunit
      autophosphorylation and prolongs the persistence of gamma-H2AX foci. If radiation
      resistant tumor cells could be sensitized by down-regulating the cellular
      level/activity of Ku/DNA-PK, this approach could be evaluated as an adjuvant to
      radiation therapy.

PMID- 17234775
TI  - Blocking CXCR4-mediated cyclic AMP suppression inhibits brain tumor growth in
      vivo.
AB  - The chemokine CXCL12 and its cognate receptor CXCR4 regulate malignant brain
      tumor growth and are potential chemotherapeutic targets. However, the molecular
      basis for CXCL12-induced tumor growth remains unclear, and the optimal approach
      to inhibiting CXCR4 function in cancer is unknown. To develop such a therapeutic
      approach, we investigated the signaling pathways critical for CXCL12 function in
      normal and malignant cells. We discovered that CXCL12-dependent tumor growth is
      dependent upon sustained inhibition of cyclic AMP (cAMP) production, and that the
      antitumor activity of the specific CXCR4 antagonist AMD 3465 is associated with
      blocking cAMP suppression. Consistent with these findings, we show that
      pharmacologic elevation of cAMP with the phosphodiesterase inhibitor Rolipram
      suppresses tumor cell growth in vitro and, upon oral administration, inhibits
      intracranial growth in xenograft models of malignant brain tumors with comparable
      efficacy to AMD 3465. These data indicate that the clinical evaluation of
      phosphodiesterase inhibitors in the treatment of patients with brain tumors is
      warranted.

PMID- 17234774
TI  - PRL-1 tyrosine phosphatase regulates c-Src levels, adherence, and invasion in
      human lung cancer cells.
AB  - Phosphatases of regenerating liver (PRL) constitute a subfamily of the protein
      tyrosine phosphatases that are implicated in oncogenic and metastatic phenotypes.
      In this study, we evaluated the role of PRL-1 in cell proliferation and
      metastatic processes in human lung cancer cells. We stably transfected human A549
      lung cancer cells with several short hairpin RNAs for PRL-1 and found decreased
      invasive activity in the resulting clones compared with control cells. In
      addition, cells with suppressed PRL-1 exhibited greater adherence and cell
      spreading on fibronectin and a decreased proliferation rate compared with control
      cells. To address possible mechanisms for the altered phenotypes, we examined
      known biochemical regulators of adhesion and invasion. Inhibition of PRL-1
      decreased c-Src and p130Cas expression and Rac1 and Cdc42 activation without any
      apparent modification of focal adhesion kinase (FAK) expression. Total tyrosine
      FAK phosphorylation and Tyr397 phosphorylation levels were continuously elevated
      in PRL-1 knockdown cells plated on fibronectin. In immunofluorescence studies,
      reduction in PRL-1 seemed to decrease cell membrane protrusions with a reduction
      in actin fiber extensions in spite of continuous phosphorylation of Tyr397 FAK,
      which could reflect reduced adhesion turnover. Our data implicate PRL-1 in the
      fundamental process of cell adhesion and migration in human lung cancer cells by
      affecting Rac1, Cdc42, and c-Src activation. These results support the hypothesis
      that PRL-1 plays an important role in maintaining the malignant phenotype by
      exploiting Src activation processes, and that PRL-1 could be a promising
      therapeutic target for cancer metastasis and cell growth.

PMID- 17234776
TI  - Increased beta1 integrin is associated with decreased survival in invasive breast
      cancer.
AB  - Aberrant microenvironments and loss of balance in cell-extracellular matrix
      signaling are associated with breast cancer invasion, metastasis, and resistance
      to therapy. We have recently shown that increased beta1 integrin signaling is
      involved in malignant progression and that inhibitory antibody to beta1 integrin
      leads to selective apoptosis and decreased proliferation in three-dimensional
      cultures and in xenograft models of breast cancer in vivo. To investigate the
      clinical importance of these findings, in the present study we examined the
      expression of beta1 integrin and extracellular beta1 integrin ligands fibronectin
      and laminin-1 in a cohort of 249 breast cancer patients who had a median follow
      up of 8.4 years. Among the 149 scorable cases, the highest beta1 integrin
      intensity score (3+ versus 0-2+) was associated with significantly decreased 10
      year overall survival of 48% versus 71% (P<0.03) and decreased disease-free
      survival of 50% versus 80% (P<0.05). Importantly, high fibronectin expression was
      associated with decreased overall and disease-free survival on univariate
      analysis (P<0.04) and beta1 integrin intensity score was significantly correlated
      with fibronectin expression (Kendall's tau-b=0.19; P=0.03). In a multivariate Cox
      proportional hazards model, beta1 integrin intensity score remained a significant
      independent predictor of overall survival [hazard ratio (HR), 1.69; 95%
      confidence interval (95% CI), 1.19-2.38; P<0.003] and disease-free survival (HR,
      1.87; 95% CI, 1.21-2.88; P<0.005). These findings show that beta1 integrin
      expression has potential prognostic value in invasive breast cancer and that
      coexpression of fibronectin may help identify patients with more aggressive
      tumors who may benefit from targeted therapy.

PMID- 17234777
TI  - A novel mechanism of resistance to epidermal growth factor receptor antagonism in
      vivo.
AB  - Epidermal growth factor receptor (EGFR) is widely expressed in a number of solid
      tumors including colorectal cancers. Overexpression of this receptor is one means
      by which a cell can achieve positive signals for survival and proliferation;
      another effective means is by constitutive activation of EGFR. We have elucidated
      the role of constitutive EGFR signaling in malignant progression by stably
      transfecting colon cancer cells with a human transforming growth factor-alpha
      cDNA (a ligand for EGFR) under repressible control by tetracycline. We show that
      constitutive expression of transforming growth factor-alpha and its subsequent
      constitutive activation of EGFR allows for cancer cell survival in response to
      environmental stress in vitro and in vivo as well. The reversal of constitutive
      EGFR activation results in the loss of downstream mitogen-activated protein
      kinase and Akt activation, and a reduction in xenograft size that is associated
      with decreased proliferation and increased apoptosis. We used CI-1033, a small
      molecule antagonist of EGFR, to dissect an activation pathway that shows the
      ability of ERBb2 to activate Akt, but not Erk in the face of EGFR antagonism.
      This novel escape mechanism is a possible explanation of why anti-EGFR therapies
      have shown disappointing results in clinical trials.

PMID- 17234778
TI  - Nur77 agonists induce proapoptotic genes and responses in colon cancer cells
      through nuclear receptor-dependent and nuclear receptor-independent pathways.
AB  - Nerve growth factor-induced Balpha (NGFI-Balpha, Nur77) is an orphan nuclear
      receptor with no known endogenous ligands; however, recent studies on a series of
      methylene-substituted diindolylmethanes (C-DIM) have identified 1,1-bis(3'
      indolyl)-1-(phenyl)methane (DIM-C-Ph) and 1,1-bis(3'-indolyl)-1-(p-anisyl)methane
      (DIM-C-pPhOCH3) as Nur77 agonists. Nur77 is expressed in several colon cancer
      cell lines (RKO, SW480, HCT-116, HT-29, and HCT-15), and we also observed by
      immunostaining that Nur77 was overexpressed in colon tumors compared with normal
      colon tissue. DIM-C-Ph and DIM-C-pPhOCH3 decreased survival and induced apoptosis
      in RKO colon cancer cells, and this was accompanied by induction of tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL) protein. The induction
      of apoptosis and TRAIL by DIM-C-pPhOCH3 was significantly inhibited by a small
      inhibitory RNA for Nur77 (iNur77); however, it was evident from RNA interference
      studies that DIM-C-pPhOCH3 also induced Nur77-independent apoptosis. Analysis of
      DIM-C-pPhOCH3-induced gene expression using microarrays identified several
      proapoptotic genes, and analysis by reverse transcription-PCR in the presence or
      absence of iNur77 showed that induction of programmed cell death gene 1 was Nur77
      dependent, whereas induction of cystathionase and activating transcription factor
      3 was Nur77 independent. DIM-C-pPhOCH3 (25 mg/kg/d) also inhibited tumor growth
      in athymic nude mice bearing RKO cell xenografts. These results show that Nur77
      active C-DIM compounds represent a new class of anti-colon cancer drugs that act
      through receptor-dependent and receptor-independent pathways.

PMID- 17234779
TI  - Activation of integrin-linked kinase is a critical prosurvival pathway induced in
      leukemic cells by bone marrow-derived stromal cells.
AB  - Integrin-linked kinase (ILK) directly interacts with beta integrins and
      phosphorylates Akt in a phosphatidylinositol 3-kinase (PI3K)-dependent manner. In
      this study, we examined the functional role of ILK activation in leukemic and
      bone marrow stromal cells on their direct contact. Coculture of leukemic NB4
      cells with bone marrow-derived stromal mesenchymal stem cells (MSC) resulted in
      robust activation of multiple signaling pathways, including ILK/Akt,
      extracellular signal-regulated kinase 1/2 (ERK1/2), signal transducers and
      activators of transcription 3 (STAT3), and Notch1/Hes. Blockade of PI3K or ILK
      signaling with pharmacologic inhibitors LY294002 or QLT0267 specifically
      inhibited stroma-induced phosphorylation of Akt and glycogen synthase kinase
      3beta, suppressed STAT3 and ERK1/2 activation, and decreased Notch1 and Hes1
      expression in leukemic cells. This resulted in induction of apoptosis in both
      leukemic cell lines and in primary acute myelogenous leukemia samples that was
      not abrogated by MSC coculture. In turn, leukemic cells growing in direct contact
      with bone marrow stromal elements induce activation of Akt, ERK1/2, and STAT3
      signaling in MSC, accompanied by significant increase in Hes1 and Bcl-2 proteins,
      which were all suppressed by QLT0267 and LY294002. In summary, our results
      indicate reciprocal activation of ILK/Akt in both leukemic and bone marrow
      stromal cells. We propose that ILK/Akt is a proximal signaling pathway critical
      for survival of leukemic cells within the bone marrow microenvironment. Hence,
      disruption of these interactions by ILK inhibitors represents a potential novel
      therapeutic strategy to eradicate leukemia in the bone marrow microenvironment by
      simultaneous targeting of both leukemic cells and activated bone marrow stromal
      cells.

PMID- 17234780
TI  - Novel chemical enhancers of heat shock increase thermal radiosensitization
      through a mitotic catastrophe pathway.
AB  - Radiation therapy combined with adjuvant hyperthermia has the potential to
      provide outstanding local-regional control for refractory disease. However,
      achieving therapeutic thermal dose can be problematic. In the current
      investigation, we used a chemistry-driven approach with the goal of designing and
      synthesizing novel small molecules that could function as thermal
      radiosensitizers. (Z)-(+/-)-2-(1-Benzenesulfonylindol-3-ylmethylene)-1
      azabicyclo[2.2.2]octan-3-ol was identified as a compound that could lower the
      threshold for Hsf1 activation and thermal sensitivity. Enhanced thermal
      sensitivity was associated with significant thermal radiosensitization. We
      established the structural requirements for activity: the presence of an N
      benzenesulfonylindole or N-benzylindole moiety linked at the indolic 3-position
      to a 2-(1-azabicyclo[2.2.2]octan-3-ol) or 2-(1-azabicyclo[2.2.2]octan-3-one)
      moiety. These small molecules functioned by exploiting the underlying biophysical
      events responsible for thermal sensitization. Thermal radiosensitization was
      characterized biochemically and found to include loss of mitochondrial membrane
      potential, followed by mitotic catastrophe. These studies identified a novel
      series of small molecules that represent a promising tool for the treatment of
      recurrent tumors by ionizing radiation.

PMID- 17234781
TI  - 2-methoxyestradiol inhibits the anaphase-promoting complex and protein
      translation in human breast cancer cells.
AB  - 2-methoxyestradiol (2ME2), an estradiol metabolite with antiproliferative and
      antiangiogenic activities, is in phase I/II clinical trials for breast cancer.
      2ME2 inhibits microtubule polymerization and causes cells to arrest in G2-M. The
      purpose of this study was to further elucidate the molecular mechanism of 2ME2.
      MDA-MB-435 breast cancer cells were treated with 2ME2 (2 micromol/L) or vehicle
      alone. RNA was extracted and genomic profiling was done using 22k Agilent
      microarrays. Expression Analysis Systematic Explorer was used to determine
      enrichment of Gene Ontology categories. Protein isolates were subjected to
      Western blot analysis. Protein synthesis was measured with a [35S]methionine
      pulse assay. An MDA-MB-435 cell line with two beta-tubulin mutations (2ME2R) was
      used to determine whether novel mechanisms were tubulin-dependent. Gene Ontology
      categories enriched include genes that regulate the mitotic spindle assembly
      checkpoint, apoptosis, and the cytosolic ribosome. The target of the mitotic
      spindle assembly checkpoint is the anaphase-promoting complex (APC). APC
      inhibition was confirmed by measuring protein levels of its targets securin and
      cyclin B1, which were increased in 2ME2-treated cells. Because gene expression in
      the cytosolic ribosome category was decreased, we evaluated whether 2ME2
      decreases protein translation. This was confirmed with a pulse assay, which
      showed decreased isotope incorporation in 2ME2-treated cells, which was
      maintained in the tubulin-resistant 2ME2R cells. APC inhibition was not
      maintained in 2ME2R cells. 2ME2 induces tubulin-dependent cell cycle arrest
      through regulation of genes involved in the mitotic spindle assembly checkpoint,
      which results in inhibition of the APC and tubulin-independent inhibition of
      protein translation.

PMID- 17234782
TI  - Synergistic tumor suppression by coexpression of FUS1 and p53 is associated with
      down-regulation of murine double minute-2 and activation of the apoptotic
      protease-activating factor 1-dependent apoptotic pathway in human non-small cell
      lung cancer cells.
AB  - FUS1 is a novel tumor suppressor gene identified in human chromosome 3p21.3
      region. Loss of expression and deficiency of posttranslational modification of
      FUS1 protein have been found in a majority of human lung cancers. Restoration of
      wild-type FUS1 in 3p21.3-deficient human lung cancer cells exhibited a potent
      tumor suppression function in vitro and in vivo. In this study, we evaluated the
      combined effects of FUS1 and tumor suppressor p53 on antitumor activity and
      explored the molecular mechanisms of their mutual actions in human non-small cell
      lung cancer (NSCLC) cells. We found that coexpression of FUS1 and p53 by N-[1
      (2,3-dioleoyloxyl)propyl]-NNN-trimethylammoniummethyl sulfate:cholesterol
      nanoparticle-mediated gene transfer significantly and synergistically inhibited
      NSCLC cell growth and induced apoptosis in vitro. We also found that a systemic
      treatment with a combination of FUS1 and p53 nanoparticles synergistically
      suppressed the development and growth of tumors in a human H322 lung cancer
      orthotopic mouse model. Furthermore, we showed that the observed synergistic
      tumor suppression by FUS1 and p53 concurred with the FUS1-mediated down
      regulation of murine double minute-2 (MDM2) expression, the accumulation and
      stabilization of p53 protein, as well as the activation of the apoptotic protease
      activating factor 1 (Apaf-1)-dependent apoptotic pathway in human NSCLC cells.
      Our results therefore provide new insights into the molecular mechanism of FUS1
      mediated tumor suppression activity and imply that a molecular therapy combining
      two or more functionally synergistic tumor suppressors may constitute a novel and
      effective strategy for cancer treatment.

PMID- 17234783
TI  - Radioiodinated versus radiometal-labeled anti-carcinoembryonic antigen single
      chain Fv-Fc antibody fragments: optimal pharmacokinetics for therapy.
AB  - Antibody fragments with optimized pharmacokinetic profiles hold potential for
      detection and therapy of tumor malignancies. We studied the behavior of three
      anti-carcinoembryonic antigen (CEA) single-chain Fv-Fc (scFv-Fc) variants (I253A,
      H310A, and H310A/H435Q; Kabat numbering system) that exhibited differential serum
      persistence. Biodistribution studies done on CEA-positive tumor xenografted mice
      revealed that the 111In-labeled I253A fragment with the slowest clearance
      kinetics (T1/2beta, 27.7 h) achieved the highest tumor uptake (44.6% ID/g at 24
      h), whereas the radiometal-labeled H310A/H435Q fragment with the most rapid
      elimination (T1/2beta, 7.05 h) reached a maximum of 28.0% ID/g at 12 h
      postinjection. The H310A protein was characterized by both intermediate serum
      half-life and tumor uptake. The 111In-based biodistribution studies showed that
      all three fragments were eliminated primarily through the liver, and hepatic
      radiometal activity correlated with the rate of fragment clearance. The 111In
      labeled H310A/H435Q protein exhibited the highest liver uptake (23.5% ID/g at 24
      h). Metabolism of the 125I-labeled scFv-Fc proteins resulted in low normal organ
      activity. Finally, the 125I/111In biodistribution data allowed for dose
      estimations, which suggest the 131I-labeled scFv-Fc H310A/H435Q as a promising
      candidate for radioimmunotherapy.

PMID- 17234784
TI  - Bortezomib inhibits cell-cell adhesion and cell migration and enhances epidermal
      growth factor receptor inhibitor-induced cell death in squamous cell cancer.
AB  - The lack of cell-cell adhesion and increased migration are key characteristics of
      cancer cells. The loss of expression of cell adhesion components and
      overexpression of components critical for cell migration, such as focal adhesion
      kinase (FAK), correlate with poor prognosis. Because alteration of protein
      turnover affects the expression levels and, in turn, may influence protein
      function, we investigated the effects of the proteasome inhibitor bortezomib on
      cell adhesion and migration in oral squamous cell cancer cell lines SCC68 and
      SCC15. Following treatment with bortezomib, protein levels of adherens junction
      components such as E-cadherin were unchanged. The desmosomal linker protein
      desmoplakin level was increased, whereas the protein level of the desmosomal
      cadherin, desmoglein 2, was diminished. Reduced desmoglein 2 levels correlated
      with the diminished strength of mechanical cell-cell adhesion. The protein level
      of the epidermal growth factor receptor (EGFR) increased after proteasome
      inhibition and EGFR inhibition with the EGFR-specific tyrosine kinase inhibitor
      PKI166 was able to restore cell-cell adhesion. Furthermore, we found that the
      combination of PKI166 with bortezomib enhanced the rate of cell death. Although
      the FAK protein level was unchanged following bortezomib treatment, recruitment
      of FAK phosphorylated at tyrosine residue 397 to the periphery of the cell was
      induced. Migration was reduced following treatment with bortezomib, which could
      potentially be explained by a prominent but disorganized actin fiber network
      revealed through immunofluorescence. Collectively, our results suggest that
      proteasome inhibition using bortezomib affects cell adhesion and cell migration
      profoundly and provides a rationale for its clinical use in conjunction with an
      EGFR inhibitor.

PMID- 17234785
TI  - Activation of Akt predicts poor outcome in neuroblastoma.
AB  - Whereas aberrant activation of the phosphatidylinositol 3'-kinase (PI3K)/Akt
      pathway, a key survival cascade, has previously been linked to poor prognosis in
      several human malignancies, its prognostic effect in neuroblastoma has not yet
      been explored. We therefore investigated the phosphorylation status of Akt, S6
      ribosomal protein as target of mammalian target of rapamycin, and extracellular
      signal-regulated kinase (ERK) in 116 primary neuroblastoma samples by tissue
      microarray and its correlation with established prognostic markers and survival
      outcome. Here, we provide for the first time evidence that phosphorylation of Akt
      at serine 473 (S473) and/or threonine 308 (T308), S6 ribosomal protein, and ERK
      frequently occurs in primary neuroblastoma. Importantly, we identified Akt
      activation as a novel prognostic indicator of decreased event-free or overall
      survival in neuroblastoma, whereas phosphorylation of S6 ribosomal protein or ERK
      had no prognostic effect. In addition, Akt activation correlated with variables
      of aggressive disease, including MYCN amplification, 1p36 aberrations, advanced
      disease stage, age at diagnosis, and unfavorable histology. Monitoring Akt at
      T308 or both phosphorylation sites improved the prognostic significance of Akt
      activation in neuroblastoma specimens compared with S473 phosphorylation.
      Parallel experiments in neuroblastoma cell lines revealed that activation of Akt
      by insulin-like growth factor (IGF)-I significantly inhibited tumor necrosis
      factor-related apoptosis-inducing ligand- or chemotherapy-induced apoptosis in a
      PI3K-dependent manner because the PI3K inhibitor LY294002 completely reversed the
      IGF-I-mediated protection of neuroblastoma cells from apoptosis. By showing that
      activation of Akt correlates with poor prognosis in primary neuroblastoma in vivo
      and with apoptosis resistance in vitro, our findings indicate that Akt presents a
      clinically relevant target in neuroblastoma that warrants further investigation.

PMID- 17234786
TI  - Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while
      expanding normal CD34+ progenitor cells.
AB  - Clinical studies involving patients with myelodysplastic syndromes or multiple
      myeloma have shown the efficacy of lenalidomide by reducing and often eliminating
      malignant cells while restoring the bone marrow function. To better understand
      these clinical observations, we investigated and compared the effects of
      lenalidomide and a structurally related analogue, CC-4047, on the proliferation
      of two different human hematopoietic cell models: the Namalwa cancer cell line
      and normal CD34+ progenitor cells. Both compounds had antiproliferative effects
      on Namalwa cells and pro-proliferative effects on CD34+ cells, whereas p21WAF-1
      expression was up-regulated in both cell types. In Namalwa cells, the up
      regulation of p21WAF-1 correlated well with the inhibition of cyclin-dependent
      kinase (CDK) 2, CDK4, and CDK6 activity leading to pRb hypophosphorylation and
      cell cycle arrest, whereas in CD34+ progenitor cells the increase of p21WAF-1 did
      not inhibit proliferation. Similarly, antiproliferation results were observed in
      two B lymphoma cell lines (LP-1 and U266) but interestingly not in normal B cells
      where a protection of apoptosis was found. Finally, CC-4047 and lenalidomide had
      synergistic effects with valproic acid [a histone deacetylase (HDAC) inhibitor]
      by increasing the apoptosis of Namalwa cells and enhancing CD34+ cell expansion.
      Our results indicate that lenalidomide and CC-4047 have opposite effects in tumor
      cells versus normal cells and could explain, at least in part, the reduction of
      malignant cells and the restoration of bone marrow observed in patients
      undergoing lenalidomide treatment. Moreover, this study provides new insights on
      the cellular pathways affected by lenalidomide and CC-4047, proposes new
      potential clinical uses, such as bone marrow regeneration, and suggests that the
      combination of lenalidomide or CC-4047 with certain HDAC inhibitors may elevate
      the therapeutic index in the treatment of hematologic malignancies.

PMID- 17234787
TI  - Sphingosine-induced apoptosis in rhabdomyosarcoma cell lines is dependent on pre
      mitochondrial Bax activation and post-mitochondrial caspases.
AB  - Sphingolipids is the collective term ascribed to components of the sphingomyelin
      cycle. Modulation of the cellular levels of individual sphingolipids can induce a
      diverse range of cellular responses including apoptosis, proliferation, and cell
      cycle arrest. We present data showing that rhabdomyosarcoma cell lines,
      independent of lineage (alveolar rhabdomyosarcoma and embryonal
      rhabdomyosarcoma), are particularly sensitive to the induction of apoptosis as a
      result of an elevation in the cellular levels of sphingosine (D-erythro
      sphingosine). Sphingosine-mediated apoptosis does not require its metabolism to
      the related proapoptotic molecule ceramide and is stereospecific because exposure
      of the rhabdomyosarcoma cell line RD to the L-erythro and DL-threo isoforms of
      sphingosine did not induce apoptosis. Importantly, for efficient induction of
      apoptosis, sphingosine required Bax activation and consequential translocation to
      the mitochondria. This resulted in selective mitochondrial release of cytochrome
      c and Smac/Diablo but not other mitochondrial related factors (apoptosis-inducing
      factor, endonuclease G, and HtrA2/Omi). Using small interfering RNA, reduced Bax
      expression conferred the impaired release of mitochondrial cytochrome c to the
      cytoplasm following sphingosine exposure, inhibiting the induction of apoptosis.
      Furthermore, dissipation of the inner mitochondrial membrane potential and
      enhanced production of reactive oxygen species were not observed. Bax activation
      and cytochrome c release were independent of caspases; however, caspase-3 and
      caspase-9 activity distal to the mitochondria was essential for the execution of
      apoptosis.

PMID- 17234788
TI  - Small ubiquitin-related modifier pathway is a major determinant of doxorubicin
      cytotoxicity in Saccharomyces cerevisiae.
AB  - Development of drug resistance is a major challenge in cancer chemotherapy using
      doxorubicin. By screening the collection of Saccharomyces cerevisiae deletion
      strains to identify doxorubicin-resistant mutants, we have discovered that the
      small ubiquitin-related modifier (SUMO) pathway is a major determinant of
      doxorubicin cytotoxicity in yeast. Mutants lacking UBA2 (SUMO activating enzyme;
      E1), UBC9 (conjugating enzyme; E2), and ULP1 and ULP2 (desumoylation peptidases)
      are all doxorubicin resistant, as are mutants lacking MLP1, UIP3, and NUP60,
      which all interact with ULP1. Most informatively, mutants lacking the SUMO E3
      ligase Siz1 are strongly doxorubicin resistant, whereas mutants of other SUMO
      ligases are either weakly resistant (siz2) or hypersensitive (mms21) to
      doxorubicin. These results suggest that doxorubicin cytotoxicity is regulated by
      Siz1-dependent sumoylation of specific proteins. Eliminating SUMO attachment to
      proliferating cell nuclear antigen or topoisomerase II does not affect
      doxorubicin cytotoxicity, whereas reducing SUMO attachment to the bud neck
      associated septin proteins has a modest effect. Consistent with these results,
      doxorubicin resistance in the siz1Delta strain does not seem to involve an effect
      on DNA repair. Instead, siz1Delta cells accumulate lower intracellular levels of
      doxorubicin than wild-type (WT) cells, suggesting that they are defective in
      doxorubicin retention. Although siz1Delta cells are cross-resistant to
      daunorubicin, they are hypersensitive to cisplatin and show near WT sensitivity
      to other drugs, suggesting that the siz1Delta mutation does not cause a general
      multidrug resistance phenotype. Cumulatively, these results reveal that SUMO
      modification of proteins mediates the doxorubicin cytotoxicity in yeast, at least
      partially, by modification of septins and of proteins that control the
      intracellular drug concentration.

PMID- 17234789
TI  - Single chemical modifications of the C-1027 enediyne core, a radiomimetic
      antitumor drug, affect both drug potency and the role of ataxia-telangiectasia
      mutated in cellular responses to DNA double-strand breaks.
AB  - The radiomimetic enediyne C-1027 induces almost exclusively DNA double-strand
      breaks (DSB) and is extremely cytotoxic. Unique among radiomimetics, ataxia
      telangiectasia mutated (ATM) is dispensable for cellular responses to C-1027
      induced DNA damage. This study explores the biological activity of three recently
      bioengineered C-1027 analogues: 7''-desmethyl-C-1027 (desmethyl), 20'-deschloro-C
      1027 (deschloro), and 22'-deshydroxy-C-1027 (deshydroxy). Each compound maintains
      the characteristic ability of radiomimetics to cleave DNA in cell-free systems,
      varying in activity from 2-fold (deschloro) to 55-fold (desmethyl) less than C
      1027. The induction of cellular DNA breaks based on pulsed field gel
      electrophoresis, comet analysis, and gammaH2AX activation was in the same rank
      order as cell-free DNA break induction, although the amount of breaks induced by
      desmethyl is greatly reduced compared with the other analogues. Despite the
      disparity in inducing DNA DSBs, all of the analogues produced G2-M cell cycle
      arrest and activated DNA DSB damage response proteins, such as p53-Ser15 and Chk2
      Thr68, at concentrations in concordance with their ability to inhibit cell
      growth. Interestingly, of the three analogues, only the desmethyl-induced DNA
      damage response was similar to C-1027, as it did not cause hypersensitive cell
      growth inhibition in the absence of ATM nor require the kinase to phosphorylate
      p53 or Chk2. These findings show that simple modifications of the chromophore of
      C-1027 can result in varied induction of, and cellular response to, DNA DSBs.

PMID- 17234790
TI  - Mcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing Bak
      activation and Bax translocation.
AB  - The Bcl-2 antagonist ABT-737 targets Bcl-2/Bcl-xL but not Mcl-1, which may confer
      resistance to this novel agent. Here, we show that Mcl-1 down-regulation by the
      cyclin-dependent kinase (CDK) inhibitor roscovitine or Mcl-1-shRNA dramatically
      increases ABT-737 lethality in human leukemia cells. ABT-737 induces Bax
      conformational change but fails to activate Bak or trigger Bax translocation.
      Coadministration of roscovitine and ABT-737 untethers Bak from Mcl-1 and Bcl-xL,
      respectively, triggering Bak activation and Bax translocation. Studies employing
      Bax and/or Bak knockout mouse embryonic fibroblasts (MEFs) confirm that Bax is
      required for ABT-737+/-roscovitine lethality, whereas Bak is primarily involved
      in potentiation of ABT-737-induced apoptosis by Mcl-1 down-regulation. Ectopic
      Mcl-1 expression attenuates Bak activation and apoptosis by ABT-737+roscovitine,
      whereas cells overexpressing Bcl-2 or Bcl-xL remain fully sensitive. Finally, Mcl
      1 knockout MEFs are extremely sensitive to Bak conformational change and
      apoptosis induced by ABT-737, effects that are not potentiated by roscovitine.
      Collectively, these findings suggest down-regulation of Mcl-1 by either CDK
      inhibitors or genetic approaches dramatically potentiate ABT-737 lethality
      through cooperative interactions at two distinct levels: unleashing of Bak from
      both Bcl-xL and Mcl-1 and simultaneous induction of Bak activation and Bax
      translocation. These findings provide a mechanistic basis for simultaneously
      targeting Mcl-1 and Bcl-2/Bcl-xL in leukemia.

PMID- 17234791
TI  - Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of
      1-methyl-tryptophan correlates with antitumor responses.
AB  - Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that contributes
      to tolerance in a number of biological settings. In cancer, IDO activity may help
      promote acquired tolerance to tumor antigens. The IDO inhibitor 1-methyl
      tryptophan is being developed for clinical trials. However, 1-methyl-tryptophan
      exists in two stereoisomers with potentially different biological properties, and
      it has been unclear which isomer might be preferable for initial development. In
      this study, we provide evidence that the D and L stereoisomers exhibit important
      cell type-specific variations in activity. The L isomer was the more potent
      inhibitor of IDO activity using the purified enzyme and in HeLa cell-based
      assays. However, the D isomer was significantly more effective in reversing the
      suppression of T cells created by IDO-expressing dendritic cells, using both
      human monocyte-derived dendritic cells and murine dendritic cells isolated
      directly from tumor-draining lymph nodes. In vivo, the d isomer was more
      efficacious as an anticancer agent in chemo-immunotherapy regimens using
      cyclophosphamide, paclitaxel, or gemcitabine, when tested in mouse models of
      transplantable melanoma and transplantable and autochthonous breast cancer. The D
      isomer of 1-methyl-tryptophan specifically targeted the IDO gene because the
      antitumor effect of D-1-methyl-tryptophan was completely lost in mice with a
      disruption of the IDO gene (IDO-knockout mice). Taken together, our findings
      support the suitability of D-1-methyl-tryptophan for human trials aiming to
      assess the utility of IDO inhibition to block host-mediated immunosuppression and
      enhance antitumor immunity in the setting of combined chemo-immunotherapy
      regimens.

PMID- 17234793
TI  - Cytochrome P450 1B1-mediated estrogen metabolism results in estrogen
      deoxyribonucleoside adduct formation.
AB  - The oxidative metabolism of estrogens has been implicated in the development of
      breast cancer; yet, relatively little is known about the mechanism by which
      estrogens cause DNA damage and thereby initiate mammary carcinogenesis. To
      determine how the metabolism of the parent hormone 17beta-estradiol (E2) leads to
      the formation of DNA adducts, we used the recombinant, purified phase I enzyme,
      cytochrome P450 1B1 (CYP1B1), which is expressed in breast tissue, to oxidize E2
      in the presence of 2'-deoxyguanosine or 2'-deoxyadenosine. We used both gas and
      liquid chromatography with tandem mass spectrometry to measure E2, the 2- and 4
      catechol estrogens (2-OHE2, 4-OHE2), and the depurinating adducts 4-OHE(2)
      1(alpha,beta)-N7-guanine (4-OHE2-N7-Gua) and 4-OHE(2)-1(alpha,beta)-N3-adenine (4
      OHE2-N3-Ade). CYP1B1 oxidized E2 to the catechol 4-OHE2 and the labile quinone 4
      hydroxyestradiol-quinone to produce 4-OHE2-N7-Gua and 4-OHE2-N3-Ade in a time-
      and concentration-dependent manner. Because the reactive quinones were produced
      as part of the CYP1B1-mediated oxidation reaction, the adduct formation followed
      Michaelis-Menten kinetics. Under the conditions of the assay, the 4-OHE2-N7-Gua
      adduct (Km, 4.6+/-0.7 micromol/L; kcat, 45+/-1.6/h) was produced 1.5 times more
      efficiently than the 4-OHE2-N3-Ade adduct (Km, 4.6+/-1.0 micromol/L; kcat, 30+/
      1.5/h). The production of adducts was two to three orders of magnitude lower than
      the 4-OHE2 production. The results present direct proof of CYP1B1-mediated, E2
      induced adduct formation and provide the experimental basis for future studies of
      estrogen carcinogenesis.

PMID- 17234792
TI  - Epigallocatechin-3-gallate enhances CD8+ T cell-mediated antitumor immunity
      induced by DNA vaccination.
AB  - Immunotherapy and chemotherapy are generally effective against small tumors in
      animal models of cancer. However, these treatment regimens are generally
      ineffective against large, bulky tumors. We have found that a multimodality
      treatment regimen using DNA vaccination in combination with chemotherapeutic
      agent epigallocatechin-3-gallate (EGCG), a compound found in green tea, is
      effective in inhibiting large tumor growth. EGCG was found to induce tumor
      cellular apoptosis in a dose-dependent manner. The combination of EGCG and DNA
      vaccination led to an enhanced tumor-specific T-cell immune response and enhanced
      antitumor effects, resulting in a higher cure rate than either immunotherapy or
      EGCG alone. In addition, combined DNA vaccination and oral EGCG treatment
      provided long-term antitumor protection in cured mice. Cured animals rejected a
      challenge of E7-expressing tumors, such as TC-1 and B16E7, but not a challenge of
      B16 7 weeks after the combined treatment, showing antigen-specific immune
      responses. These results suggest that multimodality treatment strategies, such as
      combining immunotherapy with a tumor-killing cancer drug, may be a more effective
      anticancer strategy than single-modality treatments.

PMID- 17234794
TI  - Deletion of chromosome 11q predicts response to anthracycline-based chemotherapy
      in early breast cancer.
AB  - Despite the recent consensus on the eligibility of adjuvant systemic therapy in
      patients with lymph node-negative breast cancer (NNBC) based on clinicopathologic
      criteria, specific biological markers are needed to predict sensitivity to the
      different available therapeutic options. We examined the feasibility of
      developing a genomic predictor of chemotherapy response and recurrence risk in
      185 patients with NNBC using assembled arrays containing 2,460 bacterial
      artificial chromosome clones for scanning the genome for DNA copy number changes.
      After surgery, 90 patients received anthracycline-based chemotherapy, whereas 95
      did not. Tamoxifen was administered to patients with hormone receptor-positive
      tumors. The association of genomic and clinicopathologic data and outcome was
      computed using Cox proportional hazard models and multiple testing adjustment
      procedures. Analysis of NNBC genomes revealed a common genomic signature.
      Specific DNA copy number aberrations were associated with hormonal receptor
      status, but not with other clinicopathologic variables. In patients treated with
      chemotherapy, none of the genomic changes were significantly correlated with
      recurrence. In patients not receiving chemotherapy, deletion of eight bacterial
      artificial chromosome clones clustered to chromosome 11q was independently
      associated with relapse (disease-free survival at 10 years+/-SE, 40%+/-14% versus
      86%+/-6%; P<0.0001). The 54 patients with deletion of 11q (29%) did not present
      more aggressive clinicopathologic features than those without 11q loss. The
      adverse influence of 11q deletion on clinical outcome was confirmed in an
      independent validation series of 88 patients with NNBC. Our data suggests that
      patients with NNBC with the 11q deletion might benefit from anthracycline-based
      chemotherapy despite other clinical, pathologic, or genetic features. However,
      these initial findings should be evaluated in randomized clinical trials.

PMID- 17234796
TI  - Cerebral angiogenic factors, angiogenesis, and physiological response to chronic
      hypoxia differ among four commonly used mouse strains.
AB  - Angiogenesis is a critical element for adaptation to low levels of oxygen and
      occurs following long-term exposure to mild hypoxia in rats. To test whether a
      similar response in mice occurs, CD1, 129/Sv, C57Bl/6, and Balb/c mice were
      exposed to 10% oxygen for up to 3 wk. All mice showed significant increases in
      the percentage of packed red blood cells, and CD1 and 129/Sv mice showed
      increased respiration frequency and minute volume, common physiological measures
      of hypoxia. Significant angiogenesis was observed in all strains except Balb/c
      following 3-wk exposure to chronic hypoxia. CD1 hypoxic mice had the largest
      increase (88%), followed by C57Bl/6 (48%), 129/Sv (41%), and Balb/c (12%),
      suggesting that some mice undergo more remodeling than others in response to
      hypoxia. Protein expression analysis of vascular endothelial growth factor
      (VEGF), angiopoietin (Ang)-1 and Ang2, and Tie2 were examined to determine
      whether regulation of different angiogenic proteins could account for the
      differences observed in hypoxia-induced angiogenesis. CD1 mice showed the
      strongest upregulation of VEGF, Ang2, Ang1, and Tie2, whereas Balb/c had only
      subtle increases in VEGF and no change in the other proteins. C57Bl/6 mice showed
      a regulatory response that fell between the CD1 and Balb/c mice, consistent with
      the intermediate increase in angiogenesis. Our results suggest that genetic
      heterogeneity plays a role in angiogenesis and regulation of angiogenic proteins
      and needs to be accounted for when designing and interpreting experiments using
      transgenic mice and when studying in vivo models of angiogenesis.

PMID- 17234797
TI  - Isoform switching in myofibrillar and excitation-contraction coupling proteins
      contributes to diminished contractile function in regenerating rat soleus muscle.
AB  - Postnatal development of skeletal muscle occurs through the progressive
      transformation of diverse biochemical, metabolic, morphological, and functional
      characteristics from the embryonic to the adult phenotype. Since muscle
      regeneration recapitulates postnatal development of muscle fiber, it offers an
      appropriate experimental model to investigate the existing relationships between
      diverse muscle functions and the expression of key protein isoforms, particularly
      at the single-fiber level. This study was carried out in regenerating soleus
      muscle 14 days after injury. At this intermediate stage, the regenerating muscle
      exhibited a recovery of mass greater than its force generation capacity. The
      lower specific tension of regenerating muscle suggested intrinsic defective
      excitation-contraction coupling and/or contractility processes. The presence of
      developmental isoforms of both the voltage-gated Ca(2+) channel (alpha(1)C) and
      of ryanodine receptor 3, paralleled by an abnormal caffeine contracture
      development, confirms the immature excitation-contraction coupling of the
      regenerating muscle. The defective Ca(2+) handling could also be confirmed by the
      lower sarcoplasmic reticulum caffeine sensitivity of regenerating single fibers.
      Also, regenerating single fibers revealed a lower maximal specific tension, which
      was associated with the residual presence of embryonic myosin heavy chains.
      Moreover, the fibers showed a reduced Ca(2+) sensitivity of myofibrillar
      proteins, particularly those simultaneously expressing the slow and fast isoforms
      of troponin C. The present results indicate that the expression of developmental
      proteins determines the incomplete functional recovery of regenerating soleus.

PMID- 17234795
TI  - Epidermal growth factor receptor signaling is required for microadenoma formation
      in the mouse azoxymethane model of colonic carcinogenesis.
AB  - Colonic carcinogenesis involves the progressive dysregulation of homeostatic
      mechanisms that control growth. The epidermal growth factor (EGF) receptor (EGFR)
      regulates colonocyte growth and differentiation and is overexpressed in many
      human colon cancers. A requirement for EGFR in colonic premalignancy, however,
      has not been shown. In the current study, we used a specific EGFR antagonist,
      gefitinib, to investigate this role of the receptor in azoxymethane colonic
      premalignancy. The azoxymethane model shares many clinical, histologic, and
      molecular features of human colon cancer. Mice received azoxymethane i.p. (5
      mg/kg/wk) or saline for 6 weeks. Animals were also gavaged with gefitinib (10
      mg/kg body weight) or vehicle (DMSO) thrice weekly for 18 weeks, a dose schedule
      that inhibited normal receptor activation by exogenous EGF. Compared with control
      colonocytes [bromodeoxyuridine (BrdUrd), 2.2+/-1.2%], azoxymethane significantly
      increased proliferation (BrdUrd, 12.6+/-2.8%), whereas gefitinib inhibited this
      hyperproliferation (BrdUrd, 6.2+/-4.0%; <0.005). Azoxymethane significantly
      induced pro-transforming growth factor-alpha (6.4+/-1.3-fold) and increased
      phospho-(active) EGFR (5.9+/-1.1-fold), phospho-(active) ErbB2 (2.3+/-0.2-fold),
      and phospho-(active) extracellular signal-regulated kinase (3.3+/-0.4-fold) in
      premalignant colonocytes. Gefitinib inhibited activations of these kinases by
      >75% (P<0.05). Gefitinib also significantly reduced the number of large aberrant
      crypt foci and decreased the incidence of colonic microadenomas from 75% to 33%
      (P<0.05). Gefitinib concomitantly decreased cell cycle-regulating cyclin D1 and
      prostanoid biosynthetic enzyme cyclooxygenase-2 in microadenomas, suggesting that
      these regulators are key targets of EGFR in colonic carcinogenesis. These results
      show for the first time that EGFR signaling is required for early stages of
      colonic carcinogenesis. Our findings suggest, moreover, that inhibitors of EGFR
      might be useful in chemopreventive strategies in individuals at increased risk
      for colonic malignancies.

PMID- 17234798
TI  - Cardiorespiratory and cerebrovascular responses to acute poikilocapnic hypoxia
      following intermittent and continuous exposure to hypoxia in humans.
AB  - We tested the hypothesis that intermittent hypoxia (IH) and/or continuous hypoxia
      (CH) would enhance the ventilatory response to acute hypoxia (HVR), thereby
      altering blood pressure (BP) and cerebral perfusion. Seven healthy volunteers
      were randomly selected to complete 10-12 days of IH (5-min hypoxia to 5-min
      normoxia repeated for 90 min) before ascending to mild CH (1,560 m) for 12 days.
      Seven other volunteers did not receive any IH before ascending to CH for the same
      12 days. Before the IH and CH, following 12 days of CH and 12-13 days post-CH
      exposure, all subjects underwent a 20-min acute exposure to poikilocapnic hypoxia
      (inspired fraction of O(2), 0.12) in which ventilation, end-tidal gases, arterial
      O(2) saturation, BP, and middle cerebral artery blood flow velocity (MCAV) were
      measured continuously. Following the IH and CH exposures, the peak HVR was
      elevated and was related to the increase in BP (r = 0.66 to r = 0.88,
      respectively; P < 0.05) and to a reciprocal decrease in MCAV (r = 0.73 to r =
      0.80 vs. preexposures; P < 0.05) during the hypoxic test. Following both IH and
      CH exposures, HVR, BP, and MCAV sensitivity to hypoxia were elevated compared
      with preexposure, with no between-group differences following the IH and/or CH
      conditions, or persistent effects following 12 days of sea level exposure. Our
      findings indicate that IH and/or mild CH can equally enhance the HVR, which, by
      either direct or indirect mechanisms, facilitates alterations in BP and MCAV.

PMID- 17234800
TI  - Modulation of motoneuronal firing behavior after spinal cord injury using
      intraspinal microstimulation current pulses: a modeling study.
AB  - We simulated the effects of delivering focal electrical stimuli to the central
      nervous system to modulate the firing rate of neurons and alleviate motor
      disorders. Application of these stimuli to the spinal cord to reduce the
      increased excitability of motoneurons and resulting spasticity after spinal cord
      injury (SCI) was examined by means of a morphologically detailed computer model
      of a spinal motoneuron. High-frequency sinusoidal and rectangular pulses as well
      as biphasic charge-balanced and charge-imbalanced pulses were examined. Our
      results suggest that suprathreshold high-frequency sinusoidal or rectangular
      current pulses could inactivate the Na+ channels in the soma and initial segment,
      and block action potentials from propagating through the axon. Subthreshold
      biphasic charge-imbalanced pulses reduced the motoneuronal firing rate
      significantly (up to approximately 25% reduction). The reduction in firing rate
      was achieved through stimulation-induced hyperpolarization generated in the first
      node of Ranvier. Because of their low net DC current, these pulses could be
      tolerated safely by the tissue. To deliver charge-imbalanced pulses with the
      lowest net DC current and induce the largest reduction in motoneuronal firing
      rate, we studied the effect of various charge-imbalanced pulse parameters. Short
      pulse durations were found to induce the largest reduction in firing rate for the
      same net DC level. Subthreshold high-frequency sinusoidal and rectangular current
      pulses and low-frequency biphasic charge-balanced pulses, on the other hand, were
      ineffective in reducing the motoneuronal firing rate. In conclusion, the proposed
      electrical stimulation paradigms could provide potential rehabilitation
      interventions for suppressing the excitability of neurons to reduce the severity
      of motor disorders after injury to the central nervous system.

PMID- 17234799
TI  - Leptin receptors in human skeletal muscle.
AB  - Human skeletal muscle expresses leptin receptor mRNA; however, it remains unknown
      whether leptin receptors (OB-R) are also expressed at the protein level. Fourteen
      healthy men (age = 33.1 +/- 2.0 yr, height = 175.9 +/- 1.7 cm, body mass = 81.2
      +/- 3.8 kg, body fat = 22.5 +/- 1.9%; means +/- SE) participated in this
      investigation. The expression of OB-R protein was determined in skeletal muscle,
      subcutaneous adipose tissue, and hypothalamus using a polyclonal rabbit anti
      human leptin receptor. Three bands with a molecular mass close to 170, 128, and
      98 kDa were identified by Western blot with the anti-OB-R antibody. All three
      bands were identified in skeletal muscle: the 98-kDa and 170-kDa bands were
      detected in hypothalamus, and the 98-kDa and 128-kDa bands were detected in thigh
      subcutaneous adipose tissue. The 128-kDa isoform was not detected in four
      subjects, whereas in the rest its occurrence was fully explained by the presence
      of intermuscular adipose tissue, as demonstrated using an anti-perilipin A
      antibody. No relationship was observed between the basal concentration of leptin
      in serum and the 170-kDa band density. In conclusion, a long isoform of the
      leptin receptor with a molecular mass close to 170 kDa is expressed at the
      protein level in human skeletal muscle. The amount of 170-kDa protein appears to
      be independent of the basal concentration of leptin in serum.

PMID- 17234801
TI  - Reduced efficiency, but increased fat oxidation, in mitochondria from human
      skeletal muscle after 24-h ultraendurance exercise.
AB  - The hypothesis that ultraendurance exercise influences muscle mitochondrial
      function has been investigated. Athletes in ultraendurance performance performed
      running, kayaking, and cycling at 60% of their peak O(2) consumption for 24 h.
      Muscle biopsies were taken preexercise (Pre-Ex), postexercise (Post-Ex), and
      after 28 h of recovery (Rec). Respiration was analyzed in isolated mitochondria
      during state 3 (coupled to ATP synthesis) and state 4 (noncoupled respiration),
      with fatty acids alone [palmitoyl carnitine (PC)] or together with pyruvate
      (Pyr). Electron transport chain activity was measured with NADH in permeabilized
      mitochondria. State 3 respiration with PC increased Post-Ex by 39 and 41% (P <
      0.05) when related to mitochondrial protein and to electron transport chain
      activity, respectively. State 3 respiration with Pyr was not changed (P > 0.05).
      State 4 respiration with PC increased Post-Ex but was lower than Pre-Ex at Rec (P
      < 0.05 vs. Pre-Ex). Mitochondrial efficiency [amount of added ADP divided by
      oxygen consumed during state 3 (P/O ratio)] decreased Post-Ex by 9 and 6% (P <
      0.05) with PC and PC + Pyr, respectively. P/O ratio remained reduced at Rec.
      Muscle uncoupling protein 3, measured with Western blotting, was not changed Post
      Ex but tended to decrease at Rec (P = 0.07 vs. Pre-Ex). In conclusion, extreme
      endurance exercise decreases mitochondrial efficiency. This will increase oxygen
      demand and may partly explain the observed elevation in whole body oxygen
      consumption during standardized exercise (+13%). The increased mitochondrial
      capacity for PC oxidation indicates plasticity in substrate oxidation at the
      mitochondrial level, which may be of advantage during prolonged exercise.

PMID- 17234802
TI  - Cutaneous blood flow and sweat rate responses to exogenous administration of
      acetylcholine and methacholine.
AB  - The aim of this study was to evaluate cutaneous vasodilation and sweating
      responses to exogenous administration of acetylcholine (ACh) and methacholine
      (MCh), which have different sensitivities to endogenous cholinesterase. Four
      intradermal microdialysis probes were placed in dorsal forearm skin: two sites
      were perfused with ACh (1 x 10(-7)-1 M) and the other two with the same molar
      concentrations of MCh. Sweat rate (SR) and cutaneous blood flow were
      simultaneously assessed directly over each microdialysis membrane. Dose-response
      curves were constructed, and the effective concentration of the drug resulting in
      50% of the maximal response (EC(50)) was identified. For SR and cutaneous
      vascular conductance (CVC), there were no significant differences in EC(50)
      between sites receiving the same drug: -1.52 +/- 0.18 and -1.19 +/- 0.09 log
      molar concentration of ACh at distal and proximal sites, respectively, and -2.35
      +/- 0.24 and -2.42 +/- 0.23 log-molar concentration of MCh at distal and proximal
      sites, respectively, for SR (P > 0.05) and -3.87 +/- 0.32 and -3.97 +/- 0.27 log
      molar concentration of ACh at distal and proximal sites, respectively, and -4.78
      +/- 0.17 and -4.46 +/- 0.16 log-molar concentration of MCh at distal and proximal
      sites, respectively, for CVC (P > 0.05). However, the EC(50) for CVC and SR was
      significantly lower at the MCh than at the ACh sites. A second procedure was
      performed to confirm that differences in responses between ACh and MCh could be
      attributed to different cholinesterase sensitivities. Similarly, four
      microdialysis membranes were placed in dorsal forearm skin: two sites were
      perfused with ACh and other two with MCh. However, one of each of the ACh and MCh
      sites was also perfused with 10 microM neostigmine (an acetylcholinesterase
      inhibitor). Neostigmine at the ACh site induced a leftward shift (i.e., lower
      EC(50)) of the SR and CVC dose-response curves compared with the site treated
      with ACh alone, resulting in no difference in the EC(50) for SR and CVC between
      the ACh + neostigmine and the MCh site. These results suggest that elevations in
      SR and CVC occur earlier with MCh than with ACh treatment because of differences
      in cholinesterase susceptibility between these drugs.

PMID- 17234803
TI  - Physical activity energy expenditure may mediate the relationship between plasma
      leptin levels and worsening insulin resistance independently of adiposity.
AB  - Leptin regulates a constellation of neuroendocrine processes that control energy
      homeostasis. The infusion of leptin in rodents lacking endogenous leptin promotes
      physical activity energy expenditure (PAEE) and improves insulin signaling,
      whereas hyperleptinemia is associated with physical inactivity and insulin
      resistance (IR). We tested whether baseline leptin levels predict changes in PAEE
      and IR over time, independent of obesity. We also assessed whether the
      relationship between leptin and change in IR is mediated by PAEE. The population
      consisted of 288 nondiabetic UK Caucasian adults (mean age: 49.4 yr; SD: 0.7 yr),
      in whom leptin, insulin, glucose, PAEE (via heart rate monitoring with individual
      calibration by indirect calorimetry), and anthropometric characteristics had been
      measured at baseline and 5 yr later. In linear regression models, baseline leptin
      levels inversely predicted follow-up PAEE (P = 0.033). On average, individuals
      with low leptin levels (below sex-specific median) increased their daily activity
      35% more during the 5-yr follow-up period than those with above-median leptin
      levels. Baseline leptin level also predicted worsening IR (fasting, 30-min, and 2
      h insulins, and homeostasis model assessment-IR; all P < 0.01). Associations were
      independent of potential confounders, such as adiposity, age, and sex. Including
      baseline PAEE as a cofactor in the leptin-insulin models reduced the strength (1
      4% reduction) and significance of the associations, suggesting that PAEE mediates
      the leptin-insulin relationships. Hyperleptinemia predicts a relative decline in
      PAEE and worsening insulin resistance, possibly via shared molecular pathways.

PMID- 17234804
TI  - Ventilatory and perceptual responses to cycle exercise in obese women.
AB  - The main purpose of this study was to examine the relative contribution of
      respiratory mechanical factors and the increased metabolic cost of locomotion to
      exertional breathlessness in obese women. We examined the relationship of
      intensity of breathlessness to ventilation (VE) when exertional oxygen uptake
      (VO2) of obesity was minimized by cycle exercise. Eighteen middle-aged (54+/-8
      yr, mean+/-SD) obese [body mass index (BMI) 40.2+/-7.8 kg/m2] and 13 age-matched
      normal-weight (BMI 23.3+/-1.7 kg/m2) women were studied. Breathlessness at higher
      submaximal cycle work rates was significantly increased (by>or=1 Borg unit) in
      obese compared with normal-weight women, in association with a 35-45% increase in
      Ve and a higher metabolic cost of exercise. Obese women demonstrated greater
      resting expiratory flow limitation, reduced resting end-expiratory lung volume
      (EELV)(by 20%), and progressive increases in dynamic EELV during exercise: peak
      inspiratory capacity (IC) decreased by 16% (0.39 liter) of the resting value.
      VE/VO2 slopes were unchanged in obesity. Breathlessness ratings at any given VE
      or VO2 were not increased in obesity, suggesting that respiratory mechanical
      factors were not contributory. Our results indicate that in obese women,
      recruitment of resting IC and dynamic increases in EELV with exercise served to
      optimize operating lung volumes and to attenuate expiratory flow limitation so as
      to accommodate the increased ventilatory demand without increased breathlessness.

PMID- 17234805
TI  - Fat metabolism and acute resistance exercise in trained men.
AB  - The purpose of this study was to investigate the effect of acute resistance
      exercise (RE) on lipolysis within adipose tissue and subsequent substrate
      oxidation to better understand how RE may contribute to improvements in body
      composition. Lipolysis and blood flow were measured in abdominal subcutaneous
      adipose tissue via microdialysis before, during, and for 5 h following whole body
      RE as well as on a nonexercise control day (C) in eight young (24 +/- 0.7 yr),
      active (>3 RE session/wk for at least 2 yr) male participants. Fat oxidation was
      measured immediately before and after RE via indirect calorimetry for 45 min.
      Dialysate glycerol concentration (an index of lipolysis) was higher during (RE:
      200.4 +/- 38.6 vs. C: 112.4 +/- 13.1 micromol/l, 78% difference; P = 0.02) and
      immediately following RE (RE: 184 +/- 41 vs. C: 105 + 14.6 micromol/l, 75%
      difference; P = 0.03) compared with the same time period on the C day. Energy
      expenditure was elevated in the 45 min after RE compared with the same time
      period on the C day (RE: 104.4 +/- 6.0 vs. C: 94.5 +/- 4.0 kcal/h, 10.5%
      difference; P = 0.03). Respiratory exchange ratio was lower (RE: 0.71 +/- 0.004
      vs. C: 0.85 +/- .03, 16.5% difference; P = 0.004) and fat oxidation was higher
      (RE: 10.2 +/- 0.8 vs. C: 5.0 +/- 1.0 g/h, 105% difference; P = 0.004) following
      RE compared with the same time period on the C day. Therefore, the mechanism
      behind RE contributing to improved body composition is in part due to enhanced
      abdominal subcutaneous adipose tissue lipolysis and improved whole body fat
      oxidation and energy expenditure in response to RE.

PMID- 17234806
TI  - Influence of acute inspiratory loading upon diaphragm motor-evoked potentials in
      healthy humans.
AB  - Acute prior activity of the inspiratory muscles can enhance inspiratory muscle
      strength and reduce effort perception during subsequent inspiratory efforts.
      However, the mechanisms subserving these changes are poorly understood. Responses
      to magnetic stimulation in 10 subjects were studied after an acute bout of
      nonfatiguing inspiratory muscle loading (IML), corresponding to 40% of subjects'
      initial maximal inspiratory pressure (MIP), and after an acute bout of nonloaded,
      forced inspiration (NLF). Motor-evoked potentials elicited by cortical
      stimulation (MEP(c)) and by phrenic nerve stimulation (MEP(p)) were recorded
      transcutaneously from the diaphragm before, immediately after, and 15 min after
      two sets of 30 inspiratory efforts, at rest and during an MIP effort. After IML,
      MIP increased to 113 +/- 3% (SE) of baseline and diaphragm MEP(p) (during MIP)
      significantly increased (129 +/- 10% of baseline). Diaphragmatic MEP(c) (during
      MIP), expressed as a percentage of maximal MEP(p), decreased after IML (from 29
      +/- 9% to 20 +/- 6%; P = 0.017) and after NLF (from 43 +/- 5% to 31 +/- 5%; P =
      0.032). Observations from the biceps brachi demonstrated that changes after IML
      and NLF were specific to the inspiratory muscle, since no significant changes
      were observed in biceps force generation or in MEP(p) or MEP(c) amplitudes. These
      data indicate that after IML increased global inspiratory strength is accompanied
      by increased peripheral excitability and by a dampening of corticospinal
      excitability of the diaphragm.

PMID- 17234807
TI  - Adjustable passive length-tension curve in rabbit detrusor smooth muscle.
AB  - Until the 1990s, the passive and active length-tension (L-T) relationships of
      smooth muscle were believed to be static, with a single passive force value and a
      single maximum active force value for each muscle length. However, recent studies
      have demonstrated that the active L-T relationship in airway smooth muscle is
      dynamic and adapts to length changes over a period of time. Furthermore, our
      prior work showed that the passive L-T relationship in rabbit detrusor smooth
      muscle (DSM) is also dynamic and that in addition to viscoelastic behavior, DSM
      displays strain-softening behavior characterized by a loss of passive stiffness
      at shorter lengths following a stretch to a new longer length. This loss of
      passive stiffness appears to be irreversible when the muscle is not producing
      active force and during submaximal activation but is reversible on full muscle
      activation, which indicates that the stiffness component of passive force lost to
      strain softening is adjustable in DSM. The present study demonstrates that the
      passive L-T curve for DSM is not static and can shift along the length axis as a
      function of strain history and activation history. This study also demonstrates
      that adjustable passive stiffness (APS) can modulate total force (35% increase)
      for a given muscle length, while active force remains relatively unchanged (4%
      increase). This finding suggests that the structures responsible for APS act in
      parallel with the contractile apparatus, and the results are used to further
      justify the configuration of modeling elements within our previously proposed
      mechanical model for APS.

PMID- 17234808
TI  - The identification of bacillaene, the product of the PksX megacomplex in Bacillus
      subtilis.
AB  - The approximately 80-kb pksX gene cluster in Bacillus subtilis encodes an unusual
      hybrid polyketide/nonribosomal peptide synthase that has been linked to the
      production of the uncharacterized antibiotic bacillaene. Multiple copies of this
      synthase, each similar in size to the ribosome, assemble into a single organelle
      like complex with a mass of tens to hundreds of megadaltons. The resource
      requirements of the assembled megacomplex suggest that bacillaene has an
      important biological role. By coupling a differential NMR spectroscopic technique
      with genetically manipulated strains of B. subtilis, we were able to characterize
      the structure of this unusual secondary metabolite, which could not be predicted
      by using bioinformatic analysis. We report that bacillaene is a linear molecule
      with two amide bonds: the first links an alpha-hydroxy carboxylic acid to a omega
      amino carboxylic acid containing a conjugated hexaene, and the second links the
      hexaene-containing carboxylic acid to an (omega-1) amino carboxylic acid
      containing a conjugated triene. Knowledge of bacillaene's structure has enabled
      us to annotate the pksX gene cluster and should facilitate the study of
      bacillaene's biosynthesis as well as its biological role in B. subtilis.

PMID- 17234810
TI  - Urocanic acid is a major chemoattractant for the skin-penetrating parasitic
      nematode Strongyloides stercoralis.
AB  - Host-seeking behavior by parasitic nematodes relies heavily on chemical cues
      emanating from potential hosts. Nonspecific cues for Strongyloides stercoralis, a
      nematode that infects humans and a few other mammals, include carbon dioxide and
      sodium chloride; however, the characteristic species specificity of this parasite
      suggested the existence of other, more specific cues. Here we show that the
      infective larva of S. stercoralis is strongly attracted to an extract of
      mammalian skin and that the active component in this skin extract is urocanic
      acid. Urocanic acid, a histidine metabolite, is particularly abundant in
      mammalian skin and skin secretions, suggesting that it serves as an attractant
      specific to mammalian hosts. The attractant activity of urocanic acid is
      suppressed by divalent metal ions, suggesting a possible strategy for preventing
      infection.

PMID- 17234809
TI  - An infectious retrovirus susceptible to an IFN antiviral pathway from human
      prostate tumors.
AB  - We recently reported identification of a previously undescribed gammaretrovirus
      genome, xenotropic murine leukemia virus-related virus (XMRV), in prostate cancer
      tissue from patients homozygous for a reduced activity variant of the antiviral
      enzyme RNase L. Here we constructed a full-length XMRV genome from prostate
      tissue RNA and showed that the molecular viral clone is replication-competent.
      XMRV replication in the prostate cancer cell line DU145 was sensitive to
      inhibition by IFN-beta. However, LNCaP prostate cancer cells, which are deficient
      in JAK1 and RNase L, were resistant to the effects of IFN-beta against XMRV.
      Furthermore, DU145 cells rendered deficient in RNase L with siRNA were partially
      resistant to IFN inhibition of XMRV. Expression in hamster cells of the
      xenotropic and polytropic retrovirus receptor 1 allowed these cells to be
      infected by XMRV. XMRV provirus integration sites were mapped in DNA isolated
      from human prostate tumor tissue to genes for two transcription factors (NFATc3
      and CREB5) and to a gene encoding a suppressor of androgen receptor
      transactivation (APPBP2/PAT1/ARA67). Our studies demonstrate that XMRV is a virus
      that has infected humans and is susceptible to inhibition by IFN and its
      downstream effector, RNase L.

PMID- 17234811
TI  - A functional study of plasma-membrane calcium-pump isoform 2 mutants causing
      digenic deafness.
AB  - Ca2+ enters the stereocilia of hair cells through mechanoelectrical transduction
      channels opened by the deflection of the hair bundle and is exported back to
      endolymph by an unusual splicing isoform (w/a) of plasma-membrane calcium-pump
      isoform 2 (PMCA2). Ablation or missense mutations of the pump cause deafness, as
      described for the G283S mutation in the deafwaddler (dfw) mouse. A deafness
      inducing missense mutation of PMCA2 (G293S) has been identified in a human
      family. The family also was screened for mutations in cadherin 23, which
      accentuated hearing loss in a previously described human family with a PMCA2
      mutation. A T1999S substitution was detected in the cadherin 23 gene of the
      healthy father and affected son but not in that of the unaffected mother, who
      presented instead the PMCA2 mutation. The w/a isoform was overexpressed in CHO
      cells. At variance with the other PMCA2 isoforms, it became activated only
      marginally when exposed to a Ca2+ pulse. The G293S and G283S mutations delayed
      the dissipation of Ca2+ transients induced in CHO cells by InsP3. In organotypic
      cultures, Ca2+ imaging of vestibular hair cells showed that the dissipation of
      stereociliary Ca2+ transients induced by Ca2+ uncaging was compromised in the dfw
      and PMCA2 knockout mice, as was the sensitivity of the mechanoelectrical
      transduction channels to hair bundle displacement in cochlear hair cells.

PMID- 17234813
TI  - Capillary electrophoresis reveals changes in individual mitochondrial particles
      associated with skeletal muscle fiber type and age.
AB  - Capillary electrophoresis (CE) with postcolumn laser-induced fluorescence
      detection (LIF) was used to analyze single skeletal muscle fibers from young and
      old rats. Due to selective labeling of mitochondria with 10-N-nonyl acridine
      orange, the zeptomole (10(-21) mole) sensitivity, and the high separation power,
      three properties of individual mitochondrial particles were revealed: the number,
      the distributions of cardiolipin, and their electrophoretic mobilities. Type I
      fibers had more mitochondrial particles and cardiolipin per particle than did
      type IIb fibers from rats of similar age. Individual fibers of the same fiber
      type from young rats contained more mitochondrial particles and cardiolipin per
      particle than did fibers from old rats. There were fiber type-specific and age
      specific differences in the electrophoretic mobility of individual mitochondrial
      particles. The CE-LIF results of individual mitochondrial particles are the first
      of their kind in that they reveal fiber type-specific and age-specific
      differences that are not obviously noticed in bulk measurements of heterogeneous
      tissues.

PMID- 17234812
TI  - Critical role of PA28gamma in hepatitis C virus-associated steatogenesis and
      hepatocarcinogenesis.
AB  - Hepatitis C virus (HCV) is a major cause of chronic liver disease that frequently
      leads to steatosis, cirrhosis, and eventually hepatocellular carcinoma (HCC). HCV
      core protein is not only a component of viral particles but also a
      multifunctional protein because liver steatosis and HCC are developed in HCV core
      gene-transgenic (CoreTg) mice. Proteasome activator PA28gamma/REGgamma regulates
      host and viral proteins such as nuclear hormone receptors and HCV core protein.
      Here we show that a knockout of the PA28gamma gene induces the accumulation of
      HCV core protein in the nucleus of hepatocytes of CoreTg mice and disrupts
      development of both hepatic steatosis and HCC. Furthermore, the genes related to
      fatty acid biosynthesis and srebp-1c promoter activity were up-regulated by HCV
      core protein in the cell line and the mouse liver in a PA28gamma-dependent
      manner. Heterodimer composed of liver X receptor alpha (LXRalpha) and retinoid X
      receptor alpha (RXRalpha) is known to up-regulate srebp-1c promoter activity. Our
      data also show that HCV core protein enhances the binding of LXRalpha/RXRalpha to
      LXR-response element in the presence but not the absence of PA28gamma. These
      findings suggest that PA28gamma plays a crucial role in the development of liver
      pathology induced by HCV infection.

PMID- 17234815
TI  - Lower prevalence of epsilon 4 allele of apolipoprotein E gene in healthy, longer
      lived individuals of Hellenic origin.
AB  - Apolipoprotein E (ApoE), and especially its epsilon4 isoform, is considered a
      risk factor predisposing to coronary heart disease. We hypothesized that the
      absence of epsilon4 allele offers a better chance for longer life. So we compared
      the prevalence of ApoE genotypes in 80 healthy aged individuals (HAI) (>80 years)
      and 391 Greek adults (median age 43 years) with ApoE genotype distribution
      consistent with the Hardy-Weinberg equilibrium (chi(2) = 5.93, p >.05). ApoE
      genotypes were comparable in both groups with the exception of E3/3 and E3/4,
      which were significantly higher (87.50% vs 75.99%, p =.025) and lower (5.00% vs
      13.19%, p =.036), respectively, in HAI. The epsilon2 and epsilon3 allele
      frequencies were not different between the groups. The epsilon4 allele was
      significantly less frequent in HAI compared to controls (3.1% vs 8.58%, p =.020).
      Our results indicate an unfavorable effect of epsilon4 allele on longevity that
      may be attenuated by environmental and/or other genetic factors.

PMID- 17234814
TI  - Antiapoptotic effect of implanted embryonic stem cell-derived early
      differentiated cells in aging rats after myocardial infarction.
AB  - This study tested whether implanted embryonic stem cell-derived early
      differentiated cells (EDCs) lead to improvement in cardiac function by preventing
      cardiac apoptosis in aging rats after myocardial infarction. Cardiac apoptosis
      after transplantation of EDCs was assessed in situ by terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end-labeling reaction (TUNEL) staining as
      well as by measurements of protein levels of cleaved caspases 3, Bax, and Bcl-2.
      Our results indicate that cell transplantation improved cardiac function at 6
      months observation. The frequency of apoptotic cells in the peri-infarcted
      myocardium 3 days after cell transplantation was significantly decreased in the
      cell transplantation group. EDC therapy decreased the protein levels of cleaved
      caspase 3 and Bax, and increased the level of Bcl-2 in comparison to myocardial
      infarction control. Additionally, the number of apoptotic cells decreased
      significantly in cardiomyocytes precocultured with EDCs. This study demonstrates
      that functional improvement of EDC transplantation may at least in part be
      related to a reduction in cardiomyocyte apoptosis.

PMID- 17234816
TI  - Integrin-linked kinase induces both senescence-associated alterations and
      extracellular fibronectin assembly in aging cardiac fibroblasts.
AB  - Integrin-linked kinase (ILK) is an integrin-binding cytoplasmic protein that is
      involved in regulating numerous cellular processes and extracellular matrix
      accumulation. We reported that ILK may be involved in cellular senescence, but
      whether ILK is the cause of senescence or an accompanying phenomenon still
      remains to be explored. Here, RNA interference and gene transfer techniques were
      used to knock down and overexpress ILK in 3-month-old and 28-month-old rat
      primary cardiac fibroblasts. The results show that, in younger cells, ILK
      overexpression induces larger cell shapes, lower proliferation capacity, and
      higher levels of enzymatic beta-galactosidase activity, and increases basal p53
      and p21 protein levels, whereas knock-down of ILK prevents phenotypic changes
      typical of senescence in aging cells. In addition, ILK could induce the
      cytoskeleton proteins to organize into dense, thick bundles of filaments, which
      contribute to cellular enlargement and extracellular fibronectin assembly. The
      results indicate that ILK can accelerate the process of cellular senescence.

PMID- 17234817
TI  - Effect of deleterious mutations on life span in Drosophila melanogaster.
AB  - Evolutionary theories of aging assume that the accumulation of deleterious
      mutations will reduce life span. We tested this assumption in Drosophila
      melanogaster by a newly designed mating scheme, in which mutations accumulate on
      the Binscy balancer X chromosome in heterozygous females in the absence of
      selection and recombination. We found that the life span of Binscy/RY(L) males
      from this cross decreased faster than the life span of their sibling controls
      over time in two of three runs, and that there was an age-specific increase in
      mortality in the Binscy/RY(L) males with time in one of three runs. Therefore,
      the accumulation of deleterious mutations can decrease life span by increasing
      fragility and can cause age-specific changes in mortality. These results support
      the evolutionary theory of aging.

PMID- 17234818
TI  - Longevity and correlated frailty in multigenerational families.
AB  - Multigenerational pedigrees provide an opportunity for assessing the effects of
      unobserved environmental and genetic effects on longevity (i.e., frailty). This
      article applies Cox proportional hazards models to data from three-generation
      pedigrees in the Utah Population Database using two different frailty
      specification schemes that account for common environments (shared frailty) and
      genetic effects (correlated frailty). In a model that includes measures of
      familial history of longevity and both frailty effects, we find that the variance
      component due to genetic factors is comparable to the one attributable to shared
      environments: Standard deviations of the correlated and the shared frailty
      distributions are 0.143 and 0.186, respectively. Through simulations, we also
      show a greater reduction in the bias of parameter estimates for fixed covariates
      through the use of the correlated frailty model.

PMID- 17234819
TI  - Apolipoprotein A1 is a stronger prognostic marker than are HDL and LDL
      cholesterol for cardiovascular disease and mortality in elderly men.
AB  - The aim of this study was to compare apolipoprotein A1 (ApoA1) and B (ApoB) with
      high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein
      cholesterol (LDL-C) as markers for cardiovascular mortality and morbidity in
      elderly men. We analyzed serum ApoA1, ApoB, total cholesterol, HDL-C, and LDL-C
      in a group of 77-year-old men (n = 785). The results were correlated with data
      from the Swedish cause of death registry. Receiver-operating characteristic
      curves showed that, of the studied serum markers, ApoA1 was the best predictor
      for ischemic heart disease mortality (area under the curve = 0.724, 95%
      confidence interval, 0.691-0.755). There were also significant correlations
      between the apolipoproteins and other known risk markers for cardiovascular
      disease such as triglycerides, high-sensitivity C-reactive protein (hsCRP), and
      cystatin C. Serum ApoA1 is a better risk marker than are ApoB, ApoB/ApoA1 ratio,
      HDL-C, and LDL-C for cardiovascular disease and mortality in elderly men.

PMID- 17234820
TI  - Elucidating the pathophysiology of delirium and the interrelationship of delirium
      and dementia.

PMID- 17234821
TI  - Serum biomarkers for delirium.
AB  - This narrative review examines serum biomarkers for the diagnosis and monitoring
      of delirium. Serum biomarkers for delirium fall into three major groups: 1) those
      that are present or elevated prior to disease onset-risk markers, 2) those that
      rise with onset and fall with recovery-disease markers, and 3) those that rise in
      proportion to the consequences of disease-end products. As risk markers, we
      examine serum chemistries and genetic risk markers. As disease markers, we
      examine serum anticholinergic activity, amino acids, melatonin, cytokines,
      cortisol, and gene expression. As end products of delirium, we examine markers of
      neuronal injury. Finally, we discuss methodological and biostatistical
      considerations for future biomarker studies. Identifying accurate biomarkers for
      delirium may shed further light into its pathophysiology and on the
      interrelationship between delirium and dementia.

PMID- 17234822
TI  - The role of neuroimaging in elucidating delirium pathophysiology.
AB  - Understanding of delirium pathogenesis remains limited despite improved
      diagnosis, and elucidation of risk factors and prognosis. Major advances in
      neuroimaging offer the possibility of probing the mechanisms and networks
      involved in delirium and hence improving understanding of this often devastating
      syndrome. This review describes the current literature of imaging studies in
      delirium and related conditions, introduces some of the newer capabilities of
      neuroimaging with magnetic resonance imaging, positron emission tomography, and
      single photon emission computed tomography, and discusses how these techniques
      may be applied to the study of delirium. Despite considerable challenges in
      patient recruitment, study design, intersubject variability, and scanner and
      contrast agent availability, imaging offers great potential for the
      identification and clarification of pathogenic mechanisms of delirium and its
      long-term sequelae.

PMID- 17234823
TI  - Cerebral perfusion changes in older delirious patients using 99mTc HMPAO SPECT.
AB  - BACKGROUND: Prior studies describe variable cerebral blood flow changes in
      delirium. This study aims to investigate cerebral blood flow changes in older
      hospitalized patients with delirium, the population in which most cases of
      delirium occur. METHODS: Participants included hospitalized general medical
      patients aged 65 years and older with documented delirium and no relevant medical
      conditions or preexisting abnormalities on neuroimaging prospectively studied
      using 99mTc HMPAO single photon emission computed tomography (SPECT) scans
      obtained during and after resolution of delirium. Twenty-two patients enrolled in
      the study, of whom six completed both scans. All participants underwent
      neuropsychological assessment immediately prior to SPECT scanning. SPECT images
      were compared across all participants during delirium; for patients completing
      paired scans, within-patient comparisons were made. RESULTS: Visual assessment of
      SPECT scans revealed perfusion abnormalities in frontal (5 participants) or
      parietal regions (6 participants); scans were normal in 11 participants (50%).
      Region-of-interest analysis identified reduced blood flow (p <.01) in the left
      inferior frontal, right temporal, right occipital, and pontine regions. Analysis
      of paired scans revealed reversible abnormalities in three participants (p
      <.001), with decreased right parietal perfusion in two participants and increased
      left parietal perfusion in one participant. CONCLUSIONS: The results of this
      study of a small group of general medical patients are suggestive that frontal or
      parietal cerebral perfusion abnormalities occur in delirium, and these findings
      need to be confirmed by future, larger studies. These results may help to improve
      basic understanding of delirium pathophysiology, to identify long-term changes,
      and to evaluate response to treatment over time.

PMID- 17234824
TI  - Isoflurane-induced apoptosis: a potential pathogenic link between delirium and
      dementia.
AB  - BACKGROUND: Dementia and delirium have been postulated to share common
      pathophysiologic mechanisms; however, identification of these unifying mechanisms
      has remained elusive. The inhalation anesthetic isoflurane has been shown to
      enhance beta-amyloid protein (Abeta) oligomerization and generation, to
      potentiate the cytotoxicity of Abeta, and to induce apoptosis. To address the
      molecular mechanisms of dementia and delirium associated with anesthesia and
      surgery, we assessed whether the Abeta fibrillar aggregation inhibitor Congo red
      can attenuate isoflurane-induced caspase-3 activation in H4 human neuroglioma
      cells overexpressing human beta-amyloid precursor protein (APP). METHODS: H4
      human neuroglioma cells stably transfected to express human full-length wild-type
      APP were exposed to 2% isoflurane for 6 hours. The cells were harvested at the
      end of the treatment. Caspase-3 activation was measured with quantitative Western
      blotting. RESULTS: We found that isoflurane induces cellular apoptosis in a dose
      dependent manner, and that Congo red inhibits isoflurane-induced apoptosis in H4
      human neuroglioma cells overexpressing APP. Interestingly, Congo red also
      inhibits staurosporine-induced apoptosis. CONCLUSION: The demonstration that
      isoflurane contributes to well-described mechanisms of Alzheimer's
      neuropathogenesis provides a plausible link between the acute effects of
      anesthesia, a well-described risk factor for delirium, and the more long-term
      sequelae of dementia. These findings suggest that isoflurane-induced Abeta
      oligomerization and apoptosis may contribute to the risk of postoperative
      cognitive dysfunction and provide a potential pathogenic link between delirium
      and dementia.

PMID- 17234826
TI  - When the mind goes inept.

PMID- 17234825
TI  - Does educational attainment contribute to risk for delirium? A potential role for
      cognitive reserve.
AB  - BACKGROUND: The objective of this study was to determine if level of educational
      attainment, a marker of cognitive reserve, was associated with the cumulative
      risk of delirium among hospitalized elders. METHODS: We performed a secondary
      analysis of two hospital-based studies. The first (study 1) was an observational
      study involving 491 admissions. The second study (study 2) involved consecutive
      admissions assigned to the usual care condition in a controlled clinical trial,
      and included 461 persons. All participants were elderly (aged 70+) and free from
      delirium at admission. The outcome was the occurrence of delirium, as rated by
      the Confusion Assessment Method during hospitalization. RESULTS: In study 1 and
      2, 22% and 14% of persons developed delirium (cumulative incidence),
      respectively. In both studies, risk of delirium was higher among persons with
      fewer years of education. Controlling for the effect of age, sex, dementia,
      comorbidity, and severity of illness, each year of completed education was
      associated with a 0.91 lower odds of delirium (95% confidence interval: 0.87,
      0.95): compared to persons with 12 years of education, persons with 7 years of
      education had 1.6-fold increased odds of delirium (95% confidence interval: 1.4,
      2.0). CONCLUSION: Hospitalized older persons with low educational attainment are
      at increased risk for delirium relative to persons with more education. This
      finding may have implications for the role of cognitive reserve in characterizing
      individual differences in risk for delirium.

PMID- 17234827
TI  - Dementia epidemiology research: it is time to modify the focus of research.
AB  - The incidence and prevalence of dementia are increasing. There is an urgent need
      to develop a preventive strategy. The identification of modifiable risk factors
      must therefore be a high priority. Newer imaging techniques provide an
      opportunity to identify subclinical manifestations of "dementias" that can be
      limited to the risk factors and subsequent clinical disease. The contribution of
      vascular disease to dementia and Alzheimer's disease (AD) should be a high
      priority as it offers a potential preventive strategy. Study designs need to be
      modified, including a greater emphasis on geographic variations in AD and
      dementia based on imaging studies, longitudinal studies of successful aging
      without cardiovascular disease (CVD) or AD, gene-environment interactions, and
      studies of unique populations that may be at lower risk because of specific
      lifestyles. Primary prevention trials for vascular disease should include a
      dementia component. Most, if not all, studies should include newer imaging
      studies.

PMID- 17234828
TI  - The temporal relationship between depression symptoms and cognitive functioning
      in older medical patients--prospective or concurrent?
AB  - BACKGROUND: Epidemiological studies remain inconclusive as to whether old age
      depression is an independent risk factor, a prodrome, or a clinical concomitant
      of cognitive impairment. The objective of this study, using repeated measures
      over a 12-month period, was to examine the short-term temporal relationship
      between depressive symptoms and cognitive impairment. METHODS: Two hundred eighty
      one medical inpatients 65 years old or older were followed up with the Hamilton
      Depression Rating Scale (HDRS) and Mini-Mental State Examination (MMSE) at
      enrollment and 3, 6, and 12 months later. A repeated-measures mixed linear
      regression model was used to evaluate the association between HDRS scores and
      MMSE changes over time and to test competing hypotheses about their temporal
      sequence. RESULTS: After adjusting for age, cardiovascular risk, illness
      severity, baseline physical and cognitive function, and other covariates, a one
      point increase in HDRS score (baseline mean +/- standard deviation: 14.4 +/- 7.4)
      was associated with a lower MMSE score (-0.03, 95% confidence interval, -0.07 to
      0.00) at the same time points, but not with the MMSE at subsequent time points
      (all p values >.40). There were no statistically significant interactions
      detected between follow-up time and HDRS scores measured at baseline or during
      follow-up. These results were confirmed in alternative models using dynamic
      measures of both HDRS and MMSE changes over each successive follow-up interval.
      CONCLUSIONS: These findings suggest that the short-term relationship between
      depression symptoms and cognitive functioning may be concurrent or temporary,
      rather than prospective or protracted, consistent with the clinical concomitant
      hypothesis.

PMID- 17234829
TI  - The ACTIVE cognitive training trial and health-related quality of life:
      protection that lasts for 5 years.
AB  - OBJECTIVE: We evaluated the ability of the three cognitive training interventions
      (memory, reasoning, or speed of processing) fielded in the Advanced Cognitive
      Training for Independent and Vital Elderly (ACTIVE) multisite randomized
      controlled trial to protect against two thresholds of extensive decline in health
      related quality of life (HRQoL) at 2 and 5 years post-training. METHOD: Adults
      aged 65 years or older (2802) were enrolled and randomized to three cognitive
      interventions or a no-contact control group. Data on 1804 participants were
      available at both the 2- and 5-year follow-ups. HRQoL was measured by the eight
      MOS 36-Item Short-Form Health Survey (SF-36) scales. Clinically relevant decline
      on each scale was defined as a drop of > or = 0.5 standard deviations from
      baseline. Extensive HRQoL decline was defined as clinically relevant drops on (i)
      > or = 4 SF-36 scales, and (ii) > or = 3 SF-36 scales, and was assessed using
      multiple logistic regressions, weighted to adjust for potential attrition bias.
      Results. At 2 years post-training, 23.7% and 36.6% had clinically relevant drops
      on > or = 4 and > or = 3 SF-36 scales, respectively. At 5 years post-training,
      32.9% and 47.3% had clinically relevant drops on > or = 4 and > or = 3 SF-36
      scales, respectively. Participants in the speed of processing intervention arm
      were significantly less likely to have extensive HRQoL decline compared to
      participants in the control group regardless of the threshold or time period,
      whereas participants in the memory and reasoning intervention arms were
      significantly less like to have extensive HRQoL decline only at 5 years post
      training and only at the lower threshold. Conclusion. The effect of the speed of
      processing intervention was stronger and evident earlier than those for the
      memory and reasoning interventions. This result stems from the speed of
      processing intervention being the most procedural intervention, operating through
      sensory-motor elaboration and repetition, bringing about a broader pattern of
      regional brain activation. At 5 years post-training, however, all three
      interventions were successful in protecting against a lower threshold of age
      related extensive declines in HRQoL.

PMID- 17234831
TI  - Nutritive values of methionine sources.

PMID- 17234830
TI  - Cognitive domains and trajectories of functional independence in nondemented
      elderly persons.
AB  - BACKGROUND: Cognitive impairment in general is known to predict functional
      disability, but it is not clear whether performance on specific cognitive domains
      predicts future disability trends among nondemented elderly persons. METHODS: In
      a representative elderly community-based cohort over up to 10 years of follow-up,
      we examined predictors of longitudinal trajectories in ability to perform
      Instrumental Activities of Daily Living (IADL) among nondemented elderly persons.
      We used trajectory analyses to identify homogeneous groups with respect to trends
      over time in the numbers of IADL disabilities and their association with baseline
      demographics, social engagement, depression, physical well-being, and general and
      domain-specific cognitive functions. We excluded from these analyses those
      individuals found to have dementia at baseline or at any time during follow-up.
      RESULTS: Trajectory analysis revealed three homogeneous latent groups which we
      characterized as No Decline (no decline in abilities to perform IADL tasks over
      the course of study), Moderate Decline (some functional decline), and Sharp
      Decline (steep functional decline followed by death). Compared to the Sharp
      Decline group, the No Decline group was associated with higher baseline functions
      in all cognitive domains, and the Moderate Decline group was associated with
      higher baseline functions in all cognitive domains except psychomotor speed and
      naming. The Moderate and No Decline groups did not differ on any cognitive
      measure. CONCLUSION: Among community dwelling elderly persons who remained free
      from dementia throughout the study, poorer scores in all cognitive domains
      predicted sharp functional decline followed by death.

PMID- 17234832
TI  - Effects of activity on avian gastrocnemius tendon.
AB  - Physical activity and its relationship to animal health is a continuous concern
      of the food animal industry. This study investigated the relationship between
      broiler (meat-type chicken) activity to the structural integrity of the
      gastrocnemius tendon. Birds were exposed to treadmill pacing to determine if
      increased mobilization would increase tendon strength and improve its resistance
      to soft tissue injury. One hundred eighty broilers raised under normal commercial
      housing conditions were forced to walk on a treadmill 30 min/d, 5 d/wk for 3 wk,
      beginning at 3 wk of age. The treadmill treatment did affect the growth rate of
      the broilers. At the end of the study, the average body mass of the treatment
      birds was 9% less than the average body mass of the control birds, and the
      average length of the treatment shanks was 5% less than those from the control
      birds. Biomechanical parameters were measured and used to determine changes in
      the structural and material integrity of the tendons. The treadmill treatment did
      not affect tendon toughness, stiffness, relaxation behavior, and failure
      strength, but treatment did appear to affect tendon geometry, in which 33% of the
      treadmill treatment tendons had an increased amount of tissue near the
      bifurcation. The treadmill treatment did not affect the amount of procollagen
      within the tendon, and no cellular anomalies were found.

PMID- 17234833
TI  - Foam-based mass emergency depopulation of floor-reared meat-type poultry
      operations.
AB  - Current control strategies for avian influenza and other highly contagious
      poultry diseases often include quarantine, depopulation, and disposal of infected
      birds. For biosecurity reasons, on-farm depopulation and disposal methods are
      preferred. The options for mass depopulation are limited, as reported by the
      "2000 Report of the AVMA Panel on Euthanasia." Current depopulation techniques
      may have excessive labor requirements, are not appropriate for all house types,
      and may not be suitable for large-scale emergency implementation. A procedure has
      been developed that uses foam to rapidly form a blanket over the birds. The
      procedure requires relatively few people, can be performed in a variety of house
      types, and is compatible with in-house composting. Results from 2 experiments
      using foam for depopulation are presented in this paper. These studies have shown
      that foams are comparable to the CO(2) polyethylene tent procedure in time to
      death in small groups and that the foam is faster as group size increases. Adding
      CO(2) to the foam does not enhance its efficacy. Based on corticosterone levels,
      the study also showed that the foams are no more stressful than the CO(2)
      depopulation method. Necropsy and histological examination of birds indicated
      that blood was present to some degree in the trachea, syrinx, and bronchial tree
      in broilers subjected to foam with CO(2), foam without CO(2), and CO(2)
      polyethylene tent methods of depopulation. Foam caused a rapid onset of airway
      occlusion. In both foam- and CO(2)-euthanized broilers, lesions are consistent
      with anoxia or hypoxia. This suggests that foam acts by physically induced
      hypoxia, whereas CO(2) causes chemically induced hypoxia.

PMID- 17234834
TI  - Effects of phosphorus level and phytase in broiler breeder rearing and laying
      diets on live performance and phosphorus excretion.
AB  - The effects of a reduced dietary nonphytate phosphorus (NPP) level and inclusion
      of phytase on broiler breeder performance and P concentrations in the litter and
      manure were investigated. Ross 308 broiler breeder pullets and Ross 344 cockerels
      were placed sex-separate in a blackout growing house and fed standard starter and
      grower diets to 9 wk of age. At 10 wk of age, 4 treatments (A, B, C, D) were
      assigned to each of 4 floor pens of 68 pullets and 1 pen of 50 cockerels. From 10
      to 21 wk, treatments A to D contained 0.37, 0.27, 0.27, and 0.17% NPP,
      respectively, with 300 phytase units (FTU)/kg of phytase added to treatments B
      and D. At 21 wk of age, birds were photostimulated and transferred to a two
      thirds slat-litter breeder house with 16 pens of 60 pullets and 6 cockerels. A
      laying diet was fed from 22 to 64 wk and NPP levels of treatments A to D were
      adjusted to 0.37, 0.27, 0.19, and 0.09%, respectively, and phytase addition to
      treatments B and D was increased to 500 FTU/kg. Analysis of the litter from
      growing pens showed no effect on litter total P when phytase replaced 0.1% of
      NPP. However, decreasing the dietary NPP by 0.1% without phytase reduced the
      litter total P by 18%. Water-soluble P (WSP) and the WSP:total P ratio decreased
      when the grower dietary NPP level was reduced to 0.17% with added phytase and was
      correlated with litter moisture levels in growing pens. During the laying period,
      a reduction in NPP from 0.37 to 0.09% with added phytase reduced both the manure
      total P and WSP by 42%. Hen-day egg production was highest on the lowest NPP diet
      with phytase, but fertility decreased when the dietary NPP was reduced below
      0.37%. Results showed that phytase inclusion in a broiler breeder laying diet at
      the expense of all added P from dicalcium phosphate reduced the manure total P
      and WSP concentrations by 42%, with no effect on the number of chicks produced
      per hen housed.

PMID- 17234835
TI  - Comparison of the performance of 1966- versus 2003-type turkeys when fed
      representative 1966 and 2003 turkey diets: growth rate, livability, and feed
      conversion.
AB  - Body weight, livability, and feed conversion of a randombred control turkey line
      (RBC2) started in 1966 at The Ohio State University was compared with that of
      modern commercial turkeys hatched in 2003 when fed representative 1966- and 2003
      type diets from hatch (March 5, 2003) through 196 d of age. Each pen of modern
      turkeys consisted of 5 birds each of the Nicholas, British United Turkeys of
      America, and Hybrid strains. Eight groups (i.e., 2 strains (RBC2 vs. modern), 2
      sexes, and 2 dietary regimens) were randomly assigned into each of 4 blocks of 8
      litter floor pens (32 total) for growout. Using the BW performance of the 2
      strains on the modern feed as the basis, the study showed that the 2003 turkeys
      were approximately twice as heavy as the 1966 RBC2 at the 4 slaughter ages and
      that tom weights have increased by 186, 208, 227, and 241 g/yr, and hen weights
      have increased by 164, 179, 186, and 205 g/yr at 112, 140, 168, and 196 d of age,
      respectively, over the past 37 yr. Cumulative feed conversion (kg of feed/kg of
      BW) was approximately 20% better in the 2003 tom turkey on the 2003 feed (2.638)
      than in the RBC2 tom on the 1966 feed (3.278) at 20 wk of age. Feed efficiency to
      11 kg of BW in the 2003 toms (2.132 at 98 d of age) was approximately 50% better
      than in the RBC2 toms (4.208 at 196 d of age). The number of days to reach that
      weight was halved during this period of time. Growth performance during the
      different periods of the study appeared to be strongly affected by type of feed
      used and seasonal changes in ambient temperature. Overall livability was very
      good for all groups, but the mortality level of the RBC2 was consistently higher,
      although not significantly so, than for the modern birds.

PMID- 17234836
TI  - A comparison of the immune response of 2003 commercial turkeys and a 1966
      randombred strain when fed representative 2003 and 1966 turkey diets.
AB  - The immunological performance of modern turkeys (one-third each of the Nicholas
      Turkey, British United Turkeys of America, and Hybrid Turkey strains) hatched in
      2003 (2003 strain) was compared with that of a randombred control turkey strain
      (RBC2) established in calendar year 1966, when fed representative 1966 and 2003
      type diets. The 2003 strain had a higher BW and bursa of Fabricius weight
      relative to total BW compared with the RBC2 strain (P = 0.0001) when measured at
      12 and 13 d of age, respectively. Total antibody response against SRBC did not
      differ between strains, nor were any differences observed in the IgM antibody
      levels either during a primary or secondary SRBC challenge. However, RBC2 poults
      had higher IgG levels (P = 0.02) than the 2003 strain at 7 d post secondary SRBC
      challenge. No significant differences were observed in the phytohemagglutinin
      phosphate-mediated toe-web lymphoblastic response. However, the 2003-strain
      turkeys seemed to have a better swelling response (P = 0.06) than the RBC2-strain
      turkeys when measured at 24 h post phytohemagglutinin phosphate injection. The
      modern turkeys also had higher mononuclear phagocytic system function, as
      measured by clearance of carbon particles from the bloodstream 5 min post
      intravenous injection of colloidal carbon (P = 0.02). These results indicate that
      selection over the years of turkeys for improved performance traits has had no
      adverse effects on most of the immune system indicators when examined prior to
      sexual maturity in the current study.

PMID- 17234837
TI  - Development and performances of a Japanese quail line homozygous for the diabetes
      insipidus (di) mutation.
AB  - A strain of Japanese quail with the polyuria disorder (excessive urination) was
      developed from founders that regurgitated water spontaneously. A back-cross with
      a nonpolyuric quail line showed that the polyuric strain was fixed for an
      autosomal recessive mutation that also induced polydipsia (excessive drinking).
      Plasma levels and brain mRNA contents for avian Arg vasotocin were little
      affected by the mutation, but plasma avian Arg vasotocin was 13-fold higher and
      brain mRNA contents were significantly increased in both normal and mutant quail
      following a 24-h water deprivation. Affected and normal birds had similar
      performance traits (egg production and quality, feed intake, and gross carcass
      traits), but residual feed consumption was higher in polydipsic males. These
      results are consistent with the hypothesis that this strain was fixed for a
      mutation similar to the di gene described in the chicken and which induces
      nephrogenic diabetes insipidus. This new strain of Japanese quail might
      constitute a convenient model for the analysis of the underlying mechanisms of
      the disorder in birds and for comparative study with mammals.

PMID- 17234838
TI  - Genome-wide linkage analysis to identify chromosomal regions affecting phenotypic
      traits in the chicken. III. Skeletal integrity.
AB  - Two unique chicken F(2) populations generated from a broiler breeder male line
      and 2 genetically distinct inbred (>99%) chicken lines (Leghorn and Fayoumi) were
      used for whole genome QTL analysis. Twelve phenotypic skeletal integrity traits
      (6 absolute and 6 relative traits) were measured or calculated, including bone
      mineral content, bone mineral density, tibia length, shank length, shank weight,
      and shank length:shank weight. All traits were also expressed as a percentage of
      BW at 8 wk of age. Birds were genotyped for 269 microsatellite markers across the
      entire genome. The QTL affecting bone traits in chickens were detected by the QTL
      express program. Significance levels were obtained using the permutation test.
      For the 12 traits, a total of 56 significant QTL were detected at the 5%
      chromosome-wise significance level, of which 14 and 10 were significant at the 5%
      genome-wise level for the broiler-Leghorn cross and broiler-Fayoumi cross,
      respectively. Phenotypic variation for each trait explained by all detected QTL
      across the genome ranged from 12.0 to 35.6% in the broiler-Leghorn cross and 2.9
      to 31.3% in the broiler-Fayoumi cross. Different QTL profiles identified between
      the 2 related F(2) crosses for most traits suggested that genetic background is
      an important factor for QTL analysis. Study of associations of biological
      candidate genes with skeletal integrity traits in chickens will reveal new
      knowledge of understanding biological process of skeletal homeostasis. The
      results of the current study have identified markers for bone strength traits,
      which may be used to genetically improve skeletal integrity in chickens by MAS,
      and to identify the causal genes for these traits.

PMID- 17234839
TI  - Genome-wide linkage analysis to identify chromosomal regions affecting phenotypic
      traits in the chicken. IV. Metabolic traits.
AB  - The current study is a comprehensive genome analysis to detect QTL affecting
      metabolic traits in chickens. Two unique F(2) crosses generated from a commercial
      broiler male line and 2 genetically distinct inbred lines (Leghorn and Fayoumi)
      were used in the present study. The plasma glucagon, insulin, lactate, glucose,
      tri-iodothyronine, thyroxine, insulin-like growth factor I, and insulin-like
      growth factor II concentrations at 8 wk were measured in the 2 F(2) crosses.
      Birds were genotyped for 269 microsatellite markers across the entire genome. The
      program QTL Express was used for QTL detection. Significance levels were obtained
      using the permutation test. For the 10 traits, a total of 6 and 9 significant QTL
      were detected at a 1% chromosome-wise significance level, of which 1 and 6 were
      significant at the 5% genome-wise level for the broiler-Leghorn cross and broiler
      Fayoumi cross, respectively. Most QTL for metabolic traits in the present study
      were detected in Gga 2, 6, 8, 9, 13, and Z for the broiler-Leghorn cross and Gga
      1, 2, 4, 7, 8, 13, 17, and E47 for the broiler-Fayoumi cross. Phenotypic
      variation for each trait explained by all QTL across genome ranged from 2.73 to
      14.08% in the broiler-Leghorn cross and from 6.93 to 21.15% in the broiler
      Fayoumi cross. Several positional candidate genes within the QTL region for
      metabolic traits at the 1% chromosome-wise significance level are biologically
      associated with the regulation of metabolic pathways of insulin,
      triiodothyronine, and thyroxine.

PMID- 17234840
TI  - Genetic characteristics of the ostrich population using molecular methods.
AB  - A genetic analysis was performed on Polish ostriches from the 3 principal ostrich
      breeds: red-, blue-, and black-necks. The analysis was based on 2 molecular
      methods: DNA fingerprinting and microsatellites. The DNA fingerprinting patterns
      were obtained using the restriction enzyme HinfI and Jeffrey's 33.15 probe. The
      second method consisted of a PCR procedure, for which 5 VIAS-OS primers specific
      to the ostrich were used. The PCR products were separated on polyacrylamide gel
      using ALFexpress (Authomated Laser Fluorescent DNA Sequencer). The study aimed at
      assessing the genetic variability within and among the 3 ostrich breeds as well
      as evaluating the genetic distance between them, and represents the first report
      on the genetic characteristics of the ostrich breeds. The results obtained by
      both methods showed considerable compatibility, especially with regard to the
      relationship among the breeds analyzed. The diversity within breeds, obtained on
      the basis of the DNA fingerprinting analysis, proved to be low. Among the ostrich
      populations analyzed, the highest variability potential was observed for black
      necked ostriches (the mean diversity of patterns amounted to 29.04%, whereas the
      mean heterozygosity was 0.30) and the lowest was observed for the red-necks. The
      largest genetic similarity was recorded between red- and blue-necked ostriches,
      but the greatest genetic distance was between the red- and black-necks. This
      means that the use of birds of those breeds in crosses should result in the
      highest heterotic effect. Both of these methods measured the genetic distance
      between the analyzed ostrich breeds that was expected from the geographic origin
      of these birds. The results obtained in the present study showed that both
      analytic methods used can be successfully applied when elaborating on the genetic
      characteristics of the ostrich.

PMID- 17234841
TI  - The effect of low-density broiler breeder diets on performance and immune status
      of their offspring.
AB  - Effects of low-density broiler breeder diets on offspring performance and
      mortality were studied using 2,100 female and 210 male Cobb 500 breeders. Breeder
      treatments involved 4 experimental groups and a control group with normal density
      diets (ND, 2,600 kcal of AME/kg during rearing and 2,800 kcal of AME/kg during
      laying). In treatment 2, nutrient densities were decreased by 12% (LD12) and 11%
      (LD11) during the rearing and laying periods, respectively, whereas in treatment
      3, nutrient densities were decreased by 23% (LD23) and 21% (LD21) during the
      rearing and laying periods, respectively. The nutrient density in these
      treatments was decreased through inclusion of palm kernel meal, wheat bran, wheat
      gluten feed, and sunflower seed meal in the diets. Treatment 4 included diets
      with the same nutrient densities as in treatment 2 but included oats and sugar
      beet pulp (LD12(OP) and LD11(OP)). In treatment 5, the same low-density diet was
      given to the breeders as in treatment 2 during the rearing period, but it was
      followed by a normal density diet during the laying period (LD12-ND). Treatments
      were applied from 4 to 60 wk of age. On low-density diets, offspring showed an
      increased 1-d-old weight. As compared with offspring of breeders that received
      ND, the d 38 live weight of chickens from 29-wk-old breeders fed LD11 was
      improved. Mortality was reduced in offspring from 60-wk-old parent stock given
      low-density diets. The IgM titers in 35-d-old offspring from eggs with a lower
      than-average weight were reduced when 29-wk-old broiler breeders were fed low
      density diets. In offspring from eggs with a higher-than-average weight from 60
      wk-old parent stock given LD11 or LD21 diets, IgM titers were higher compared
      with ND. It was concluded that low-density broiler breeder diets can improve
      offspring growth rates, reduce mortality, and reduce or increase immune
      responses, depending on breeder age and egg weight.

PMID- 17234842
TI  - On the interactions between Fusarium toxin-contaminated wheat and nonstarch
      polysaccharide hydrolyzing enzymes in diets of broilers on performance,
      intestinal viscosity, and carryover of deoxynivalenol.
AB  - Wheat was inoculated with Fusarium culmorum. Broiler diets were formulated to
      contain this Fusarium-infected wheat (FIW) or control wheat (CW) at a proportion
      of 60% and were prepared without and with an exogenous nonstarch polysaccharide
      (NSP) hydrolyzing enzyme preparation [endo-1,4-beta-xylanase (EC 3.2.1.8) 1,000
      FXU/g; ZY68, Lohmann Animal Health GmbH & Co. KG, Cuxhaven, Germany] to test the
      hypothesis that Fusarium infection-related increases in NSP hydrolyzing enzyme
      activities could compensate for the deleterious effects of the fungal-origin
      mycotoxins such as deoxynivalenol (DON). Deoxynivalenol concentration of CW and
      FIW amounted to 0.045 and 2.5 mg/kg of DM, respectively. After 35 d, the level of
      feed intake was generally lower in broilers fed the diets containing the FIW.
      Feed intake was stimulated by the addition of the NSP enzyme to both diet types.
      Similar relationships were observed for live weight gain, although the enzyme
      effect was much more pronounced for the CW-fed broilers, who performed even worse
      than the broilers fed the unsupplemented FIW. Viscosity was significantly reduced
      in the jejunum and the ileum by supplemental exogenous NSP hydrolyzing enzyme.
      However, this effect was more pronounced when the enzyme was added to the control
      diet, as indicated by the significant interactions between wheat and NSP enzyme.
      Concentrations of DON and its metabolite deepoxy-DON in plasma, bile, liver, and
      breast meat were lower than the detection limits of the applied HPLC-method.
      Overall, it can be concluded that feeding FIW might positively influence broiler
      performance and nutritional physiology, as indicated by the reduced intestinal
      viscosity and the less pronounced effects of addition of an exogenous NSP
      hydrolyzing enzyme preparation.

PMID- 17234843
TI  - Effects of low phytate barley (Hordeum vulgare L.) on zinc utilization in young
      broiler chicks.
AB  - Two 21-d experiments were conducted to evaluate the effects of low phytate barley
      (LPB) on Zn utilization by young broiler chicks and to determine the contribution
      of endogenous phytase, present in LPB. In the first experiment, ninety-six 1-d
      old male chicks were assigned to a 2 x 3 factorial arrangement of treatments (4
      pens of 4 chicks/treatment). Factors were barley type [wild-type barley (WTB) and
      LPB mutant M 955] and supplemental Zn (0, 10, or 20 mg of Zn/kg). In the second
      experiment, two hundred forty 1-d-old straight-run broiler chicks were assigned
      to a 2 x 2 x 3 factorial arrangement of treatments (4 pens of 5
      chicks/treatment). Factors were barley type (WTB and LPB), autoclave treatment
      [nonautoclaved or autoclaved (121 degrees C, 20 kg/cm(2), 20 min)], and
      supplemental Zn (0, 10 or 20 mg of Zn/kg). Barley made up 60% of the diets and
      was the only source of phytate. On average, basal diets contained 26 mg of Zn/kg.
      Feed intake and body weight gain were greater (P < 0.05) in broilers fed LPB
      compared with WTB in experiment 2. Zinc concentration in toes and tibias were
      affected (P < 0.0001) by barley type (LPB > WTB) and supplemented Zn levels (20 >
      10 > 0 mg of Zn/kg), and significant barley type x Zn interactions were also
      observed in both experiments. Substitution of LPB for WTB increased tibia and toe
      Zn by 46 and 25%, respectively, an increase comparable to that achieved with
      supplementing the diet with 20 mg of Zn/kg. No effect of autoclaving was observed
      for any variable in experiment 2. Retention of P and Zn was higher (P < 0.001) in
      chicks fed LPB compared with WTB in both experiments. Zinc retention was
      influenced (P < 0.0001) by dietary Zn, and barley type x Zn level interactions (P
      < 0.05) were observed in both experiments. Chicks fed LPB utilized more dietary
      Zn and P than those fed WTB, and this improved mineral utilization was not due to
      endogenous phytase present in barley.

PMID- 17234844
TI  - Evaluation of the efficacy of a probiotic containing Lactobacillus,
      Bifidobacterium, Enterococcus, and Pediococcus strains in promoting broiler
      performance and modulating cecal microflora composition and metabolic activities.
AB  - The aim of this work was to investigate the efficacy of a new multibacterial
      species probiotic in broiler nutrition. The probiotic contained 2 Lactobacillus
      strains, 1 Bifidobacterium strain, 1 Enterococcus strain, and 1 Pediococcus
      strain. Four hundred 1-d-old male Cobb broilers were allocated in 4 experimental
      treatments for 6 wk. The experimental treatments received a corn-soybean basal
      diet and were as follows: "control," with no other additions; "probiotic in feed
      and water," (PFW) with probiotic administered at 1 g/kg of feed for the whole
      period and in water on scheduled intervals during the first 4 wk; "probiotic in
      feed," (PF) with probiotic in feed as in PFW; and "antibiotic," (AB) with
      addition of avilamycin at 2.5 mg/kg of feed. Salinomycin Na was used as a
      coccidiostat. Each treatment had 5 replicates of 20 broilers. Treatment effects
      on parameters of broiler performance and cecal microbial ecology were determined.
      Broiler BW, feed intake, and feed conversion ratio were determined on a weekly
      and overall basis. Cecal microflora composition, concentration of volatile fatty
      acids, and activities of 5 bacterial glycolytic enzymes (alpha-galactosidase,
      beta-galactosidase, alpha-glucosidase, beta-glucosidase, and beta-glucuronidase)
      were determined at the end of the experiment. Overall, treatment PFW displayed a
      growth-promoting effect that did not differ from AB. Overall, feed conversion
      ratio in treatment AB was significantly better (P < or = 0.01) than the control
      treatment, whereas treatments PFW and PF were intermediate and not different from
      AB. Concentrations of bacteria belonging to Bifidobacterium spp., Lactobacillus
      spp., and gram-positive cocci were significantly (P < or = 0.05) higher in
      treatments PFW and PF compared with the control and AB treatments. Treatments PFW
      and PF had significantly higher specific activities of alpha-galactosidase and
      beta-galactosidase compared with the control and AB treatments. In conclusion,
      probiotic treatment PFW displayed a growth-promoting effect that was comparable
      to avilamycin treatment. In addition, treatments PFW and PF modulated the
      composition and, to an extent, the activities of the cecal microflora, resulting
      in a significant probiotic effect.

PMID- 17234845
TI  - Effects of various levels of conjugated linoleic acid supplementation on fatty
      acid content and carcass composition of broilers.
AB  - The effects of dietary conjugated linoleic acid (CLA) supplementation on growth
      performance, carcass quality, free fatty acid composition, and accumulation of
      CLA were investigated in broilers. Four hundred eighty 3-wk-old broilers were
      assigned to 4 dietary treatments (0, 0.5, 1.0, and 1.5% CLA) with 6 replicates of
      20 chickens. Feed consumption and BW were recorded at every 5-d period. On d 42,
      carcass compositions were determined from 30 birds per treatment. There were no
      significant differences in average daily feed intake among the treatments.
      However, feed conversion ratio was highly significantly different (P < 0.01)
      between treatments, and average daily gain was significantly reduced by a
      supplement of dietary CLA (P < 0.05). Live weight and percentages of carcass,
      drumstick, thigh, boneless thigh, pectoralis major, and pectoralis minor were not
      influenced by the dietary CLA. Abdominal fat was significantly reduced (P < 0.01)
      with the increased CLA level in the broilers' diets. Percentages of liver weight
      were significantly increased (P < 0.01) after the CLA treatments. Percentages of
      drumstick and boneless drumstick were significantly decreased (P < 0.05) by
      dietary CLA. In terms of free fatty acid composition in broiler meat, CLA
      addition significantly increased (P < 0.05) saturated fatty acids, especially in
      thigh muscle, whereas unsaturated fatty acids were unchanged. Accumulations of
      CLA in meat were significantly increased (P < 0.05) with increasing CLA level in
      the diet.

PMID- 17234846
TI  - Variations in the digestible sulfur amino acid requirement of broiler chickens
      due to sex, growth criteria, rearing environment, and processing yield
      characteristics.
AB  - Four experiments (Exp.) were conducted with Cobb 500 chicks to evaluate
      variations in the estimated digestible sulfur amino acid (DSAA) requirement of
      broilers due to rearing environment, sex, or growth performance during the
      starter period (7 to 19 d), and live performance response and carcass yield
      characteristics during the grower period (21 to 42 d). In the first 3 experiments
      conducted during the starter period, chicks were allocated to battery or floor
      pens, and in the fourth experiment birds were reared in floor pens. For Exp. 1,
      2, and 3 a sulfur amino acid deficient corn-soybean meal-corn gluten meal basal
      diet and for the grower experiment a corn-soybean meal-peanut meal basal diet was
      formulated to be isocaloric and isonitrogenous within experiment. Graded levels
      of DSAA ranged from 0.54 to 0.94% in Exp. 1, 0.53 to 1.03% in Exp. 2, 0.49 to
      0.89% in Exp. 3, and 0.43 to 0.83% in Exp. 4. True digestibility of the diets was
      determined using the precision-fed rooster assay. The DSAA requirements were
      estimated using 1-slope broken-line methodology. During the starter period, the
      average DSAA requirement of males and females was similar when based on the gain
      to feed ratio (G:F; 0.71 and 0.71%, respectively) and BW gain (BWG; 0.67 and
      0.67%, respectively). In Exp. 3 involving battery and floor pens, males and
      females had similar DSAA requirement estimates, but the DSAA requirement based on
      maximal G:F (0.68%) was higher than the maximal BWG requirement (0.61%). In the
      grower period, the estimated DSAA requirement for males based on G:F was higher
      than that based on BWG, but the BWG and G:F requirements were similar for
      females. The DSAA requirement estimates were similar for males and females based
      on BWG (0.55%), but the DSAA requirement based on G:F was higher for males than
      females. The DSAA requirement for maximum breast meat yield was similar for males
      (0.55%) and females (0.56%), and the requirement for maximal breast meat yield
      was similar to that for maximal BWG. The DSAA requirements were similar based on
      sex, rearing environment, or both; however, there was a difference in the
      estimated DSAA requirements between growth and carcass responses.

PMID- 17234847
TI  - Effect of increased heat processing and particle size on phosphorus
      bioavailability in corn distillers dried grains with solubles.
AB  - Previous studies have reported that increased heat processing and feeding larger
      particle size ingredients may increase the bioavailability of phytate P in some
      feedstuffs. Therefore, one chick experiment was conducted to determine the effect
      of various increased heat processing treatments on bioavailability of P in corn
      distillers dried grains with solubles (DDGS), and 2 chick experiments were
      conducted to determine the effect of particle size on bioavailability of P in
      DDGS. In addition, one precision-fed cecectomized rooster assay was conducted to
      evaluate the effects of increased heating on amino acid digestibility. For the
      chick experiments, a P-deficient cornstarch-dextrose-soybean meal basal diet
      containing 0.10% nonphytate P was supplemented with 0.0, 0.05, or 0.10% P from
      KH(2)PO(4) or 1 of 2 levels of DDGS. Diets were fed from 8 to 22 d of age, and P
      bioavailability relative to the P in KH(2)PO(4) was estimated using the standard
      curve or slope-ratio methods with tibia ash as the response variable. Increased
      heating of DDGS by autoclaving at 124 kPa and 121 degrees C for 60 to 80 min or
      by heating in a drying oven at 121 degrees C for 60 min significantly increased
      relative P bioavailability in DDGS (from 70 to as high as 91%) in several
      treatments. Amino acid digestibility, however, was greatly reduced by increased
      heating in most cases, particularly for Lys. Relative bioavailability of P was
      not significantly affected by DDGS particle sizes ranging from 542 to 837 microm.
      Our results indicated that increased heating of DDGS increased bioavailability of
      P but decreased digestibility of amino acids, particularly Lys, and that
      bioavailability of P was not affected by particle size.

PMID- 17234848
TI  - The effect of corticosterone-induced stress on amino acid digestibility in Ross
      broilers.
AB  - Two experiments (Exp.) were conducted to establish amino acid (AA) digestibility
      coefficients (DC) for broilers given corticosterone (CS)-induced stress using the
      apparent ileal digestibility assay. For Exp. 1, 192 Ross x Ross 708 male broilers
      were placed into 16 floor pens (12 birds/pen). For Exp. 2, 120 Ross x Ross 308
      male broilers were placed into 10 floor pens (12 birds/pen). Pens contained
      nipple drinkers, pan feeders, and soft-wood shavings. Both experiments were
      completely randomized designs using pen as the experimental unit. In both
      experiments, chicks were given a common starter diet from d 1 to 20. From d 21 to
      30, broilers were provided a control diet or the control + 15 mg of CS/kg of diet
      dissolved in soybean oil (8 and 5 replications/treatment in Exp. 1 and 2,
      respectively). Diets were based on corn (65.07%) and soybean meal (26.36%) and
      contained an indigestible marker (chromic oxide 0.3%). Diets were formulated to
      contain 3,175 kcal of ME, 18.5% CP, 0.79% digestible TSAA, and 1.00% digestible
      Lys. Stress validation was accomplished by measuring BW gain, feed intake, and
      liver weight on d 30. Evidence that stress occurred was apparent due to the fact
      that broilers fed CS had lower BW gain and higher liver weight than those fed
      control. On d 30, the ileal contents were removed from 3 birds/pen, pooled,
      dried, and analyzed for AA content. Amino acid DC were calculated using the
      following equation: DC = 100 -(dietary marker % x ileal AA %) / (ileal marker % x
      dietary AA %) x 100. Amino acid digestibility did not differ (P > 0.05) between
      treatments in either experiment. Based on this research, future research should
      be directed at establishing DC for other nutrients in stressed broilers or the
      effect of different nutrients on the stress response.

PMID- 17234849
TI  - Correlation of an immobilized digestive enzyme assay with poultry true amino acid
      digestibility for soybean meal.
AB  - The immobilized digestive enzyme assay (IDEA) was run on 6 soybean meal (SBM)
      samples and compared with true amino acid digestibility (TAAD) content, as
      determined using cecectomized roosters. The IDEA values were excellent TAAD
      predictors as evidenced by R(2) values of 0.90 and 0.88 for lysine and cystine,
      respectively. The original IDEA took 2.5 d to run, and therefore we modified the
      protocol to reduce the time to 18 h. This modified IDEA procedure was run on 17
      SBM samples, and IDEA values were shown to be excellent predictors of TAAD
      content. This IDEA SBM kit was validated by predicting the TAAD of 5 SBM not
      included in the 17-sample set above and the comparison of the predicted vs.
      determined TAAD. Finally, the IDEA SBM kit was used to compare the predicted TAAD
      of 338 SBM samples from around the world. The predicted lysine digestibility on
      the world survey samples ranged from 70.6 to 95.5% with an average of
      approximately 89%, and the ranges and means of the other amino acid
      digestibilities were also calculated.

PMID- 17234851
TI  - Changes in brown eggshell color as the hen ages.
AB  - The color of eggshells from eggs laid by commercial-type Hy-Line brown hens 25 wk
      of age was studied over a period of 10 mo. Color measurements were made by a
      color machine vision system and were analyzed using a mixed model to calculate
      between and within hen variances and to investigate the effect of time on shell
      color. Hens laid eggs with lighter colored shells as the flock aged, as evidenced
      by the lightness (L*) values increasing in time. A decrease in pigmentation was
      associated with a decrease in the amount of redness (a*) in the eggshell. When L*
      and a* values were corrected for egg weight, the rate of change in the L* and a*
      values decreased, indicating that size of the egg was a major factor affecting
      the color of the eggshell. These findings quantified the observations that older
      hens lay lighter colored eggs due to an increase in egg size associated with no
      proportionate change in the quantity of pigment deposited over the shell surface.
      Using a 2-stage sampling analysis and the variances between and within hens,
      sample sizes required to estimate the color of eggshells within 5% of the true
      mean were calculated. Accordingly, 11 eggs would need to be collected from each
      of the 51 hens housed for a study of brown eggshell color using the L*, a*, and
      b* (yellowness) coordinates.

PMID- 17234850
TI  - Excess dietary lysine increases growth of chicks fed niacin-deficient diets, but
      dietary quinolinic acid has no niacin-sparing activity.
AB  - Catabolism of Trp and Lys produces alpha-ketoadipic acid as an intermediary
      metabolite. An alternate pathway of Trp turnover leads to NAD synthesis. We
      hypothesized that excess Lys might improve the conversion of Trp to niacin by
      causing a buildup of alpha-ketoadipic acid, thereby endproduct inhibiting the
      main Trp catabolic pathway and resulting in more niacin synthesis from Trp. Six
      bioassays were carried out in which 12 to 20 chicks were fed each experimental
      diet from d 8 to d 20 or 21 posthatching. The basal diet (4 mg/kg of bioavailable
      niacin) used for all assays was a semipurified corn gluten meal diet fortified
      with crystalline amino acids to 22.5% CP and 0.96% true digestible Lys. Assay 1
      through 3 established the requirements for digestible Trp (0.16%) and
      bioavailable niacin (19.5 mg/kg) and showed that 0.96% digestible Lys was
      adequate for chick growth in the presence of adequate Trp and niacin. The fourth
      assay was done to determine the effect of 1% Lys (1.25% food-grade L-Lys x HCl)
      on niacin utilization. Excess Lys improved (P < 0.01) weight gain of niacin
      deficient chicks. The fifth assay showed that 1% excess food-grade Lys improved
      weight gain in niacin-deficient (4 mg/kg) chicks but depressed weight gain in
      niacin-adequate (24 mg/kg) chicks (niacin x Lys interaction, P < 0.01). In assay
      6, chicks fed 6 mg/kg of niacin gained faster (P < 0.01) than control chicks, but
      neither quinolinic acid (100 mg/kg) nor picolinic acid (4,200 mg/kg) elicited a
      response. These results suggest that excess Lys leads to an accumulation of alpha
      ketoadipic acid, which causes endproduct inhibition of the main Trp catabolic
      pathway to CO(2), therefore increasing flux of 2-amino-3-carboxymuconate
      semialdehyde to NAD.

PMID- 17234852
TI  - Acute heat stress induces oxidative stress and decreases adaptation in young
      white leghorn cockerels by downregulation of avian uncoupling protein.
AB  - Reactive oxygen species-induced damage of cells and molecules is one of the
      mechanisms responsible for the decline in an animal's performance due to heat
      stress. Mitochondria are the main producers of cellular superoxide, a process
      that is sensitive to proton motive force, and this superoxide production can be
      decreased by mild uncoupling. We studied the effects of heat stress on the
      production of mitochondrial superoxide as well as heat stress effects on the
      expression of avian uncoupling protein (avUCP) and avian A nucleotide
      translocator (avANT) in skeletal muscles of chicks and young cockerels. Male
      White Leghorn (Julia) chicks at 16 d and cockerels at 87 d of age were exposed to
      acute heat stress, 34 degrees C for 18 h, or kept at moderate ambient temperature
      (25 and 21 degrees C, respectively). There was no difference in mitochondrial
      superoxide production between heat-exposed and control chicks, whereas
      significant differences were observed in the case of young cockerels. Greater
      substrate-independent superoxide production was found in muscle mitochondria from
      heat-stressed young cockerels. In chicks, neither avUCP nor avANT transcript
      expression was changed by heat exposure, whereas in young cockerels avUCP
      transcript was decreased, but avANT transcript level was not changed. Thus, in
      heat-stressed young cockerels, increased mitochondrial superoxide production was
      accompanied by downregulation of avUCP. Taken together, these results suggest
      that exposure of young cockerels to heat stress stimulates mitochondrial
      superoxide production, possibly via downregulation of avUCP. Chicks with
      persistent avUCP expression, on the other hand, are relatively better adapted to
      high temperature. It can be assumed that appropriate expression of avUCP may
      alleviate overproduction of mitochondrial superoxide and could help birds adapt
      to oxidative stress resulting from acute heat stress.

PMID- 17234853
TI  - Gene expression in breast muscle and duodenum from low and high feed efficient
      broilers.
AB  - This study was conducted to evaluate messenger RNA (mRNA) expression of genes
      that are involved in energy metabolism and mitochondrial biogenesis: avian
      adenine nucleotide translocator (avANT), cytochrome oxidase III (COX III),
      inducible nitric oxide synthase (iNOS), peroxisome proliferator-activated
      receptor-gamma (PPAR-gamma), avian PPAR-gamma coactivator-1alpha (avPGC-1alpha),
      and avian uncoupling protein in breast muscle and duodenum of broilers with low
      and high feed efficiency (FE). Total RNA was extracted from snap-frozen tissues
      from male broilers with low (0.55 +/- 0.01) and high (0.72 +/- 0.01) FE (n = 8
      per group). Total RNA was reverse-transcribed using oligo(dT), random primers, or
      both followed by real-time reverse transcription-PCR. Protein oxidation, measured
      as protein carbonyls, was also evaluated in duodenal mucosa. Protein carbonyls
      were higher in low FE mucosa in tissue homogenate and mitochondrial fraction. The
      mRNA expression of iNOS and PPAR-gamma in the duodenum was lower in the low FE
      broilers, with no differences in avANT, COX III, and avPGC-1alpha. In contrast,
      expression of avANT and COX III mRNA in breast muscle was lower in low FE
      broilers with no differences in iNOS, PPAR-gamma, and avPGC-1alpha. The avian
      uncoupling protein in breast muscle was higher in low FE birds (P = 0.068). These
      results indicate that there are differences in the expression of mRNA encoding
      for mitochondrial transcription factors and proteins in breast muscle and
      duodenal tissue between low and high FE birds. The differences that were observed
      may also reflect inherent metabolic and gene regulation differences between
      tissues.

PMID- 17234854
TI  - A comparison of breast muscle characteristics in three broiler great-grandparent
      lines.
AB  - Genetic selection of broiler chickens has led to a gross overdevelopment of the
      broiler breast muscle pectoralis major. This may have resulted in increased
      myopathy and detrimental effects on meat quality. The present study examined 3
      commercial great-grandparent lines (lines A, B, and C). Lines A and B are female
      lines, and line C is a male line. The mean BW of line C (2.7 kg) was
      significantly greater than those of lines A and B (both 2.3 kg). However, the
      mean breast yield of both lines B and C (8.9 and 8.7%, respectively) was
      significantly greater than that of line A (6.9%). Line B therefore matched the
      meat yield of line A while maintaining a high reproductive capacity. The mean
      breast fillet weight of line A (169 g) was significantly lower than lines B (207
      g) and C (235 g). No differences were observed between lines in either mean fiber
      size or amount of connective tissue. Therefore, additional fibers must provide
      the additional weight in the breast fillet of lines B and C, compared with A.
      Plasma creatine kinase activity, a commonly used marker of muscle damage, was
      significantly higher in line A (1368 IU/L) than in lines B (995 IU/L) and C (982
      IU/L). However, qualitative evaluations of muscle pathology revealed no
      differences among lines. Selection for increased embryonic muscle fiber number,
      rather than for increased radial fiber growth, could improve growth potential and
      may also alleviate muscle damage.

PMID- 17234855
TI  - Suitability of pea starch and calcium alginate as antimicrobial coatings on
      chicken skin.
AB  - The effect of incorporating trisodium phosphate (TSP) in pea starch (PS) and
      acidified sodium chlorite (ASC) in calcium alginate upon the antimicrobial
      activity of TSP and ASC was studied against a 3-strain cocktail of Salmonella
      inoculated on chicken skin. The influence of polymer coating concentration on
      skin pH, coating-skin adhesion, and coating absorption upon antimicrobial
      performance were investigated. Aqueous solutions of 0.5 to 4.8% (wt/vol) PS were
      prepared with 10% (wt/vol) TSP (PS + TSP coating), and alginate + ASC coatings
      contained 1% (wt/vol) calcium chloride in 1,200 ppm of ASC mixed with an aqueous
      solution of 0.5, 1.0, or 1.5% (wt/vol) sodium alginate. Coating drops (10 microL)
      were placed on chicken skin thighs, and the angle formed by the tangent of the
      liquid surface at the skin interface (contact angle) was measured using a digital
      camera to assess coating-skin adhesion. Excised skins were mounted in a ring
      holder, and 5 mL of the coatings was applied to the skin. Weight changes in the
      skins that were related to coating absorptiveness were recorded. The TSP
      dissolved in 3.5% PS and ASC in 1% alginate reduced Salmonella by 1.6 log cfu/g
      and 1.4 log cfu/g, respectively, within 24 h. These reductions were significantly
      greater than those caused by TSP or ASC alone in water for up to 120 h. In
      coatings, TSP and ASC caused significant elevation or reduction of skin surface
      pH for up to 120 h, respectively. The TSP destabilized PS with 88% of the coating
      having dripped from the skin 1 h later. Coatings with 0.5% PS were absorbed
      quickly by the skin and had high skin adhesion, whereas those with >3.5% PS had
      low skin adhesion and slow absorption. Alginate coatings with or without ASC were
      stable, and about 50% of the coating weight was retained at 120 h. The latter
      coatings appeared to have low absorptiveness because the skin gained
      approximately 1.0% of its weight within 60 min following application. These
      findings indicate that effects of the agents in coatings on skin pH, the extent
      of coating adhesion, and absorption may contribute to overall antimicrobial
      behaviors.

PMID- 17234856
TI  - Frequency and enumeration of Campylobacter species from processed broiler
      carcasses by weep and rinse samples.
AB  - Frequency and numbers of Campylobacter spp. were assessed per freshly processed,
      contaminated broiler carcass. Campylobacter-positive flocks were identified by
      cecal sample analysis at slaughter. These flocks had been tested as Campylobacter
      negative at 4.1 +/- 0.9 d prior to slaughter. Levels of contamination were
      estimated using 2 sampling approaches per carcass: (1) free weep fluids and (2)
      whole-carcass, 100 mL of distilled water rinses. Estimations of counts were
      determined by directly plating dilutions of weeps and rinses onto Campy-Cefex
      agar and incubating the plates at 41.5 degrees C under microaerobic atmosphere.
      Confirmation was provided by latex agglutination to quantify levels per
      milliliter of weep and per 100 mL of rinse. Thirty-two slaughter groups (
      approximately 20 carcasses per group) were compared from 2003 to 2004. The
      Campylobacter-positive weep frequency was 84.8%, whereas the frequency for rinse
      samples was 74.4% (P < 0.001). Enumeration of Campylobacter spp. on positive
      samples ranged from 0.70 to 6.13 log(10) cfu/mL of weep (geometric mean of 2.84)
      and from 2.30 to 7.72 log(10) cfu/100 mL of rinse (geometric mean of 4.38). The
      correlations between weep and rinse were 0.814 with 0.5 mL of rinse and 0.6294
      when applying 0.1 mL of rinse The quantitative regression analyses for these 2
      corresponding tests were log(10) rinse (for 0.5 mL of inoculum) = 1.1965 log(10)
      weep + 0.4979, and log(10) rinse (for 0.1 mL of inoculum) = 1.322 log(10) weep -
      0.1521. FlaA SVR sequencing of isolates indicated that the same genotypes were
      found in weep and rinse samples. Weep and rinse sampling led to different
      proportions of Campylobacter-positive carcasses detection, but we demonstrated
      that this difference was reduced by increasing the amount of rinse fluid used for
      plating.

PMID- 17234857
TI  - Preparation of immunoglobulin Y from egg yolk using ammonium sulfate
      precipitation and ion exchange chromatography.
AB  - The objective of this study was to develop an economical, simple, and large-scale
      separation method for IgY from egg yolk. Egg yolk diluted with 9 volumes of cold
      water was centrifuged after adjusting the pH to 5.0. The supernatant was added
      with 0.01% charcoal or 0.01% carrageenan and centrifuged at 2,800 x g for 30 min.
      The supernatant was filtered through a Whatman no. 1 filter paper and then the
      filtrate was concentrated to 20% original volume using ultrafiltration. The
      concentrated solution was further purified using either cation exchange
      chromatography or ammonium sulfate precipitation. For the cation exchange
      chromatography method, the concentrated sample was loaded onto a column
      equilibrated with 20 mM citrate-phosphate buffer at pH 4.8 and eluted with 200 mM
      citrate-phosphate buffer at pH 6.4. For the ammonium sulfate precipitation
      method, the concentrated sample was twice precipitated with 40% ammonium sulfate
      solution at pH 9.0. The yield and purity of IgY were determined by ELISA and
      electrophoresis. The yield of IgY from the cation exchange chromatography method
      was 30 to 40%, whereas that of the ammonium sulfate precipitation was 70 to 80%.
      The purity of IgY from the ammonium sulfate method was higher than that of the
      cation exchange chromatography. The cation exchange chromatography could handle
      only a small amount of samples, whereas the ammonium sulfate precipitation could
      handle a large volume of samples. This suggests that ammonium sulfate
      precipitation was a more efficient and useful purification method than cation
      exchange chromatography for the large-scale preparation of IgY from egg yolk.

PMID- 17234858
TI  - Influence of egg shell embryonic incubation temperature and broiler breeder flock
      age on posthatch growth performance and carcass characteristics.
AB  - A study was conducted to examine the posthatch growth performance of high
      yielding broilers when eggs were incubated at 3 different embryo temperatures
      from 2 flocks of breeders at different ages (different egg size). Two thousand,
      four hundred eggs from 2 broiler breeder flocks (29 and 57 wk of age) of the same
      high-yielding strain (Cobb x Cobb) were incubated in the same incubator for 16 d
      at 37.5 degrees C. Following candling, the eggs from the 2 flocks were
      transferred into 3 hatcher cabinets at starting temperatures of 36.5 degrees C
      (low, L), 37.6 degrees C (middle, M), and 38.7 degrees C (high, H) and adjusted
      to achieve a shell temperature of 37.5 degrees C (L), 38.6 degrees C (M), and
      39.7 degrees C (H) using an infrared thermometer. All chicks were taken off at 21
      d of incubation, randomized into floor pens, and reared for 44 d. Body weights,
      feed intake, and feed conversion were determined at 21, 35, and 44 d of age. Body
      weight of birds from the H treatment was significantly less at 21, 35, and 44 d
      compared with the M birds. Birds in the L group weighed significantly less at 35
      and 44 d compared with the M birds. Progeny from the older breeder flock had
      significantly greater BW at 1, 21, and 35 d of age, but had only numerically
      greater BW at 44 d when compared with birds from the younger flock. Feed
      conversion for the H birds was significantly higher from 0 to 21 d of age
      compared with the M and L birds. Broilers from the 29-wk-old breeder flock had
      lower cumulative feed conversion values than the birds from the 57-wk-old flock.
      No significant differences in mortality were observed. Posthatch performance
      appears to be affected by hatcher environment as determined by embryo shell
      temperature.

PMID- 17234859
TI  - Consumer perception versus scientific evidence about alternatives for manual
      catching of broilers in Belgium.
AB  - Commercial broiler chickens are exposed to a number of potential stressors prior
      to slaughter, including catching, crating, and transportation. To ameliorate
      animal welfare and prevent product quality loss during these processes, numerous
      scientific studies have been performed. As a result, different technical
      innovations have been presented such as mechanical catching instead of manual
      catching. The success of a catching machine as an alternative for manual catching
      of broilers will not only depend on its economic, animal, and human welfare
      benefits but also on its acceptance by society and consumers. The aim of this
      research was to assess if individuals' subjective perceptions of catching methods
      align with objective scientific facts. This research was focused on questions and
      issues related to the consumers' expected bottlenecks and motives for accepting
      these technologies after being exposed to video segments of each catching method.
      In general, the gap between consumer perception and scientific evidence related
      to manual and mechanical catching is limited. For those bottlenecks where science
      is inconclusive, respondents also have no explicit preference. Despite absence of
      major gaps between consumer perception and expert knowledge, preferences of
      particular consumer segments do not align well with scientific evidence. This
      holds in particular for female, younger, urban individuals who attach high
      importance to animal welfare issues.

PMID- 17234860
TI  - The effects of breeding systems and stocking density on some blood parameters of
      rock partridges (Alectoris graeca).
AB  - In this study, the effects of breeding systems and stocking density on some blood
      parameters of rock partridges [total protein, total cholesterol, triglyceride,
      urea, glucose, calcium, phosphorus, alkaline phosphatase (ALP), sodium, chlorine,
      potassium, aspartate amino transferase (AST), and alanine amino transferase
      (ALT)] were investigated. For this purpose, blood samples of 18-wk-old male rock
      partridges, which were bred on the ground and in cages with 3 different stocking
      densities (group I: 15 partridges/m(2); group II: 20 partridges/m(2); and group
      III: 25 partridges/m(2)) were examined. Breeding method of rock partridges was
      found to have significant effects on blood total protein, (P < 0.05), total
      cholesterol (P < 0.05), triglyceride (P < 0.01), urea (P < 0.01), glucose (P <
      0.05), calcium (P < 0.05), phosphorus (P < 0.01), ALP (P < 0.05), sodium (P <
      0.01), chlorine (P < 0.05), and potassium (P < 0.01) levels, whereas it was found
      to have no significant effect on blood AST and ALT levels (P > 0.05). Stocking
      density of rock partridges was also found to affect significantly the levels of
      blood total protein, total cholesterol, triglyceride, urea, glucose, calcium,
      phosphorus, ALP, sodium, chlorine, and potassium (P < 0.05), whereas it did not
      have a significant effect on blood AST and ALT levels (P > 0.05). When the
      breeding method of the partridges was changed from the ground to the cages and
      the stocking density was increased, it was observed that the levels of blood
      total cholesterol, triglyceride, urea, glucose, sodium, and chlorine increased,
      whereas total protein, calcium, phosphorus, ALP, and potassium levels decreased.
      It was understood that the reactions of partridges toward breeding systems and
      stocking density were different and passing from ground system to cage system,
      and the increase in stocking density caused significant changes in blood
      parameters.

PMID- 17234862
TI  - Making public health history usable: the launch of a new series in JECH.

PMID- 17234861
TI  - Cloning of chicken glucocorticoid receptor (GR) and characterization of its
      expression in pituitary and extrapituitary tissues.
AB  - Substantial evidence suggests that glucocorticoids play critical roles in the
      differentiation of somatotroph and lactotroph in embryonic pituitaries of birds.
      However, the basic information on the expression of glucocorticoid receptor (GR)
      in avian species is limited. In this study, the full-length cDNA for chicken GR
      was cloned from the chicken kidney. It encodes 772 amino acids and shares high
      homology with that of the human (73%), mouse (73%), rat (71%), rabbit (72%), and
      trout (51%) sequences. Similar to mammals, chicken GR is widely expressed in all
      adult tissues being investigated. Among the 12 tissues investigated, relatively
      high expression of GR was detected in pituitary, muscle, ovary, and kidney using
      reverse transcription-PCR assay. Using semiquantitative reverse transcription
      PCR, GR is shown to be abundantly expressed at a more or less constant level
      during embryonic pituitary development (from d 8 to 20), supporting the
      hypothesis that the expression of GR is unlikely to be a limiting factor in
      initiating the differentiation of somatotroph and lactotroph in embryonic
      pituitary of birds. Moreover, an abundant expression of GR in the whole embryos
      at earlier developmental stages (from d 2 to 5) was also detected in the present
      study, though its physiological relevance remains to be determined.

PMID- 17234863
TI  - Is it time to abandon colour categories for ethnic groups?

PMID- 17234864
TI  - Global environmental change and human health: a public health research agenda.

PMID- 17234865
TI  - Knights, knaves, pawns and queens: attitudes to behaviour in postwar Britain.
AB  - The choice agenda is currently one of the most prominent in public policy. One of
      its main architects, Julian Le Grand, has used the metaphors of knights, knaves,
      pawns and queens to characterise changing attitudes to questions of motivation
      and behaviour among public servants and service users. He has said, for example,
      that, in the immediate postwar period, public servants were perceived as public
      spirited altruists (or knights), whereas service users were seen as passive (or
      pawns). It was only in the mid-1980s that public servants came to be seen as
      essentially self-interested (knaves) and service users came to be regarded as
      consumers (queens). However, this highly influential model has undergone
      remarkably little critical scrutiny to date. This article explores the debate
      over transmitted deprivation in the 1970s to provide a historically grounded
      piece of analysis to explore the accuracy and utility of these metaphors. It
      challenges Le Grand's arguments in three respects. Firstly, a concern with
      behaviour and agency went much broader than social security fraud. Secondly, the
      metaphor of pawns is inadequate for characterising attitudes towards the poor and
      service users. Finally, Le Grand's periodisation of the postwar era also has
      serious flaws.

PMID- 17234866
TI  - Geographical epidemiology, spatial analysis and geographical information systems:
      a multidisciplinary glossary.
AB  - We provide a relatively non-technical glossary of terms and a description of the
      tools used in spatial or geographical epidemiology and associated geographical
      information systems. Statistical topics included cover adjustment and
      standardisation to allow for demographic and other background differences, data
      structures, data smoothing, spatial autocorrelation and spatial regression. We
      also discuss the rationale for geographical epidemiology and specific techniques
      such as disease clustering, disease mapping, ecological analyses, geographical
      information systems and global positioning systems.

PMID- 17234867
TI  - Assessing post-disaster consequences for health at the population level:
      experience from the AZF factory explosion in Toulouse.
AB  - BACKGROUND: A major explosion occurred in the AZF chemical factory in Toulouse in
      September 2001. A comprehensive programme of epidemiological surveillance was set
      up. OBJECTIVES: To present an overview of the programme and discuss the methods
      and potential utility of post-disaster epidemiology. The programme had three
      objectives: (1) to analyse comprehensively the short-term and long-term effects
      of air, water and secondary soil pollution on health; (2) to identify health
      problems needing special attention; and (3) to investigate the long-term direct
      and indirect effects on the population's health. METHODS: The programme was
      organised through three committees: (1) a scientific committee, (2) an executive
      programme committee and (3) an institutional committee which aimed to facilitate
      exchanges between the epidemiologists, the regional authorities, the population
      and the media. As the catastrophe was an industrial disaster that had a major
      effect on workers and companies, and also caused severe damage to many schools
      and buildings all over the city, routine and ad hoc surveillance systems were
      used and three specific ad hoc questionnaire surveys in workers, schoolchildren
      and the general population were planned. RESULTS AND CONCLUSIONS: Although the
      routine surveillance systems had limitations, several sources provided useful
      information for public health decisions and were found to be concordant with ad
      hoc epidemiological studies. Defining a victim was central to the choice of a
      programme design based on an approach either to victims of the disaster or to the
      entire population in the surrounding region. Anticipation and preparation for
      such disasters are thus required.

PMID- 17234868
TI  - Personal, social and environmental determinants of educational inequalities in
      walking: a multilevel study.
AB  - OBJECTIVE: To investigate the contribution of personal, social and environmental
      factors to mediating socioeconomic (educational) inequalities in women's leisure
      time walking and walking for transport. METHODS: A community sample of 1282 women
      provided survey data on walking for leisure and transport; educational level;
      enjoyment of, and self-efficacy for, walking; physical activity barriers and
      intentions; social support for physical activity; sporting/recreational club
      membership; dog ownership; and perceived environmental aesthetics and safety.
      These data were linked with objective environmental data on the density of public
      open space and walking tracks in the women's local neighbourhood, coastal
      proximity and street connectivity. RESULTS: Multilevel modelling showed that
      different personal, social and environmental factors were associated with walking
      for leisure and walking for transport. Variables from all three domains explained
      (mediated) educational inequalities in leisure-time walking, including
      neighbourhood walking tracks; coastal proximity; friends' social support; dog
      ownership; self-efficacy, enjoyment and intentions. On the other hand, few of the
      variables examined explained educational variations in walking for transport,
      exceptions being neighbourhood, coastal proximity, street connectivity and social
      support from family. CONCLUSIONS: Public health initiatives aimed at promoting,
      and reducing educational inequalities in, leisure-time walking should incorporate
      a focus on environmental strategies, such as advocating for neighbourhood walking
      tracks, as well as personal and social factors. Further investigation is required
      to better understand the pathways by which education might influence walking for
      transport.

PMID- 17234869
TI  - Cardiovascular risk prediction tools for populations in Asia.
AB  - BACKGROUND: Cardiovascular risk equations are traditionally derived from the
      Framingham Study. The accuracy of this approach in Asian populations, where
      resources for risk factor measurement may be limited, is unclear. OBJECTIVE: To
      compare "low-information" equations (derived using only age, systolic blood
      pressure, total cholesterol and smoking status) derived from the Framingham Study
      with those derived from the Asian cohorts, on the accuracy of cardiovascular risk
      prediction. DESIGN: Separate equations to predict the 8-year risk of a
      cardiovascular event were derived from Asian and Framingham cohorts. The
      performance of these equations, and a subsequently "recalibrated" Framingham
      equation, were evaluated among participants from independent Chinese cohorts.
      SETTING: Six cohort studies from Japan, Korea and Singapore (Asian cohorts); six
      cohort studies from China; the Framingham Study from the US. PARTICIPANTS:
      172,077 participants from the Asian cohorts; 25,682 participants from Chinese
      cohorts and 6053 participants from the Framingham Study. MAIN RESULTS: In the
      Chinese cohorts, 542 cardiovascular events occurred during 8 years of follow-up.
      Both the Asian cohorts and the Framingham equations discriminated cardiovascular
      risk well in the Chinese cohorts; the area under the receiver-operator
      characteristic curve was at least 0.75 for men and women. However, the Framingham
      risk equation systematically overestimated risk in the Chinese cohorts by an
      average of 276% among men and 102% among women. The corresponding average
      overestimation using the Asian cohorts equation was 11% and 10%, respectively.
      Recalibrating the Framingham risk equation using cardiovascular disease incidence
      from the non-Chinese Asian cohorts led to an overestimation of risk by an average
      of 4% in women and underestimation of risk by an average of 2% in men.
      INTERPRETATION: A low-information Framingham cardiovascular risk prediction tool,
      which, when recalibrated with contemporary data, is likely to estimate future
      cardiovascular risk with similar accuracy in Asian populations as tools developed
      from data on local cohorts.

PMID- 17234870
TI  - Participative risk communication in an industrial village in Sardinia.
AB  - OBJECTIVE: In Italy the law on industrial risk has emphasised the necessity of
      building a local information process to answer people's questions on safety and
      provide greater community participation in risk management. The aim of this
      research is to analyse the local population's ideas and expectations of a
      participatory approach in risk management in order to design a risk communication
      programme based on health promotion principles. DESIGN, SETTING AND PARTICIPANTS:
      The study was carry out in Portoscuso (Italy), an industrial district. A
      questionnaire was administrated through home interviews to 147 citizens. MAIN
      RESULTS: Six risk management styles were identified on the basis of citizens'
      trust in the different stakeholders. Additional parameters (importance of
      information, organisations they would trust to get information on industrial
      risks, preferred risk communication methodologies) were analysed according to the
      management styles. CONCLUSIONS: On the basis of these elements, a multi-approach
      strategy could be proposed. Each management style can have different roles. A
      programme of public forums could involve citizens with an interactive approach,
      interactive courses could involve citizens with a semi-participative approach,
      and leaflets and booklets could inform citizens oriented towards unidirectional
      communication. The participative process should always be open to new
      contributions from citizens who are not directly involved, and should allow for
      flexibility in the form and nature of partnership, as well as the details of
      implementation.

PMID- 17234871
TI  - Effectiveness of a physician-oriented feedback intervention on inappropriate
      hospital stays.
AB  - OBJECTIVE: To evaluate the effectiveness of a combined intervention to reduce
      inappropriate hospital stays. DESIGN: Quasi-experimental pre-test/post-test with
      a non-equivalent control group. SETTING: Three teaching hospitals in the National
      Health System in Alicante, Spain. STUDY PARTICIPANTS: Intervention group (2
      Surgical Units with 1451 hospital stays) and control group (1 Surgical Unit with
      1268 hospital stays). INTERVENTION: Structured oral presentation followed by
      direct feedback to surgeons about their own percentages of inappropriate stays
      and daily evaluation of appropriateness by the surgeons during their rounds. MAIN
      OUTCOME MEASURES: Reduction in the percentage of inappropriate stays identified
      by the Appropriateness Evaluation Protocol during the intervention period
      compared to the basal period. RESULTS: The intervention group reduced its
      percentage of inappropriate stays from 14.3% to 7.9% (absolute reduction: -6.40;
      95% CI -10.7 to -2.14; relative reduction: 44.8%), while no changes occurred in
      the control group. The reduction was in the number of inappropriate stays
      attributable to the patients' medical management that went from 12.7% to 5.8%
      (absolute reduction: -6.92; 95% CI -10.90 to -2.92), while no significant changes
      occurred in inappropriate stays due to other causes. CONCLUSIONS: A combined
      intervention of feedback and physician participation in appropriateness
      evaluations is effective in reducing the percentage of inappropriate hospital
      stays, particularly those attributable to conservative medical patterns at
      discharge.

PMID- 17234872
TI  - Association between childhood fatal injuries and socioeconomic position at
      individual and area levels: a multilevel study.
AB  - OBJECTIVES: To simultaneously examine the effects of area-level and individual
      level socioeconomic position on fatal injuries in children <5 years of age.
      METHODS: A retrospective cohort study based on the national birth and death
      registers of Korea. 2 667 060 children born during 1995-8 were followed up from
      birth to the 5th birthday. Cumulative incidences of fatal injuries were
      calculated, and through multilevel Poisson regression models, relative risks
      (RRs) of incidence rate were estimated according to children's sex, father's
      occupation and mother's education at individual level, and deprivation and degree
      of urbanity at area level. RESULTS: Girls had lower risk for fatal injuries than
      boys (RR 0.81; 95% confidence interval (CI) 0.75 to 0.87). Compared with children
      with fathers in non-manual occupations, those with fathers in manual (RR 1.45;
      95% CI 1.34 to 1.58) or other occupations (RR 1.35; 95% CI 1.13 to 1.62) had
      higher risk. Children with mothers who were high school graduates (RR 1.23; 95%
      CI 1.12 to 1.36) or junior school graduates (RR 1.91; 95% CI 1.66 to 2.19) had
      higher risk than those whose mothers were college graduates. After controlling
      for individual-level variables, residence in more deprived districts (RR 1.13;
      95% CI 1.05 to 1.21) or non-metropolitan regions (urban RR 1.34; 95% CI 1.22 to
      1.47 and rural RR 1.61; 95% CI 1.40 to 1.86) was significantly associated with
      increased risk. CONCLUSIONS: Both individual-level and area-level socioeconomic
      position influenced the risk for childhood fatal injuries. To reduce the
      socioeconomic inequalities and the absolute burden in Korea, universal strategies
      should receive priority, and special efforts in implementation should be directed
      towards both disadvantaged households and areas.

PMID- 17234873
TI  - The relation between family socioeconomic trajectories from childhood to
      adolescence and dental caries and associated oral behaviours.
AB  - OBJECTIVES: To investigate the influence of family socioeconomic trajectories
      from childhood to adolescence on dental caries and associated behaviours. DESIGN:
      Population-based birth cohort. SETTING: Representative sample of the population
      of subjects born in 1982 in Pelotas, Brazil. PARTICIPANTS: Adolescents (n = 888)
      aged 15 years old were dentally examined and interviewed. MAIN OUTCOME MEASURES:
      Dental caries index (DMFT), care index (F/DMFT), tooth brushing, flossing and
      pattern of dental services use. MAIN RESULTS: Adolescents who were always poor
      showed, in general, a worse pattern of dental caries, whereas adolescents who
      never were poor had a better pattern of dental caries. Adolescents who had moved
      from poverty in childhood to non-poverty in adolescence and those who had moved
      from non-poverty in childhood to poverty in adolescence had similar dental
      pattern to those who were always poor except for the pattern of dental services
      use, which was higher in the first group. In all groups girls had fewer carious
      teeth, better oral hygiene habits and higher dental services use than boys.
      CONCLUSION: Poverty in at least one stage of the lifespan has a harmful effect on
      dental caries, oral behaviours and dental services use. Belonging to upwardly
      mobile families between childhood and adolescence only contributed to improved
      dental care.

PMID- 17234874
TI  - Stronger associations between daily mortality and fine particulate air pollution
      in summer than in winter: evidence from a heavily polluted region in western
      Europe.
AB  - BACKGROUND: Numerous studies have shown a strong association between daily
      mortality and small particulate with a diameter of <10 microm (PM10) air
      pollution, but the effects of season have not always been well characterised.
      AIM: To study the shape of the association between short-term mortality and PM10
      across seasons and quintiles of outdoor temperature. DESIGN, SETTING AND
      PARTICIPANTS: Daily data on mortality (n = 354 357), outdoor temperature and PM10
      in Flanders, Belgium, from January 1997 to December 2003, were analysed across
      warm versus cold periods of the year (April-September v October-March), with
      seasons and quintiles of outdoor temperature as possible effect modifiers.
      RESULTS: There was a significant (p<0.001) interaction between PM10 and period of
      the year in relation to mortality. To allow for non-linearity, daily mean PM10
      concentrations were categorised into quartiles. Season-specific PM10 quartiles
      showed a strong and steep linear association between mortality and PM10 in summer
      and a less linear association in spring and autumn, whereas in winter the
      association was less strong and mortality was only increased in the highest PM10
      quartile. The effect sizes expressed as the percentage increase in mortality on
      days in the highest season-specific PM(10) quartile versus the lowest season
      specific PM10 quartile were 7.8% (95% CI 6.1 to 9.6) in summer, 6.3% (4.7 to 7.8)
      in spring, 2.2% (0.58 to 3.8) in autumn and 1.4% (0.06 to 2.9) in winter. An
      analysis by quintiles of temperature confirmed these effect sizes. CONCLUSION:
      The short-term effect of particulate air pollution on mortality strongly depends
      on outdoor temperature, even in a temperate climate.

PMID- 17234875
TI  - Social gradients in binge drinking and abstaining: trends in a cohort of British
      adults.
AB  - OBJECTIVE: To investigate (1) social gradients in non-drinking and binge
      drinking, and (2) changes in social gradients in drinking with increasing age.
      METHODS: British men and women born during the same week in March 1958 were
      prospectively followed up to adulthood. The frequency and amount of alcohol use
      were recorded at age 23, 33 and 42 years. Abstainers "never" drank, binge
      drinkers consumed >or=10 units (men) and >or=7 units (women) per occasion.
      Educational qualifications and occupation were reported at age 23 and 33 years.
      Logistic and repeated-measures models were used to investigate associations
      between social position and drinking status at single and multiple ages in
      adulthood. RESULTS: Less educated men and women had greater odds of being non
      drinkers at each age in adulthood, with similar gradients at ages 23-42 years. At
      23 years of age, men without qualifications had 2.94 times greater odds of non
      drinking than men with higher qualifications. Less educated men had greater odds
      of binge drinking, and gradients did not change at ages 23-42 years. At age 23
      years, less educated women had lower odds of binge drinking (odds ratio (OR) 0.67
      for women with no qualifications) than women with higher qualifications. By age
      42 years, the gradient reversed, and less educated women had higher odds of binge
      drinking (OR 2.68). CONCLUSIONS: Stable gradients in non-drinking and trends in
      gradients in binge drinking may reinforce alcohol-related health inequalities
      over time.

PMID- 17234876
TI  - Organisational downsizing and increased use of psychotropic drugs among employees
      who remain in employment.
AB  - OBJECTIVE: Organisational downsizing is common in modern work life, but its
      effect on employees' mental health is not known. The authors examined whether
      working in downsizing organisations predicts use of psychotropic drugs among
      employees who remain in employment. DESIGN, SETTING AND PARTICIPANTS: Prospective
      cohort study of municipal employees in Finland. 4783 employees worked in
      downsized units but kept their jobs after downsizing in 1993, 4271 employees lost
      their jobs during the downsizing, and 17 599 employees did not experience
      downsizing. The outcome was psychotropic drug prescriptions (antidepressants,
      anxiolytics and hypnotics) during 1994-2000 extracted from nationwide registers
      and linked to the data by means of each participant's personal identification
      number. MAIN RESULTS: After adjustment for predownsizing characteristics,
      employees who were exposed to downsizing but kept their jobs were at a higher
      risk of being prescribed psychotropic drugs (rate ratio 1.49, 95% CI 1.10 to 2.02
      in men and 1.12, 95% CI 1.00 to 1.27 in women) than those not exposed to
      downsizing. The association of downsizing was strongest with hypnotics among the
      men and with anxiolytics among the women. An increased rate of psychotropic
      prescriptions after downsizing was also seen in male workers who lost their job
      (rate ratio 1.64, 95% CI 1.19 to 2.25). CONCLUSIONS: The association between
      organisational downsizing and increased use of psychotropic drugs suggests that
      this managerial strategy may pose mental health risks among employees.

PMID- 17234877
TI  - Mortality in relation to sex in the affluent world.
AB  - BACKGROUND: This paper explores newly available data for 22 countries with
      reliably recorded mortality data. The past century saw dramatic falls in
      mortality for both males and females in the most affluent countries of the world.
      However, these falls are not consistent for both men and women and the
      inequalities in the male:female mortality ratios are not well understood. DESIGN:
      By aggregating mortality at each year of life for the 22 countries for those
      years for which reliable data were recorded (during the period 1850-1999),
      distinct patterns emerge. RESULTS: In the richer countries of the world, the
      male:female mortality ratio has been widening for all years of age, particularly
      for those born from 1942 onwards. Specific cohort effects are clearly
      identifiable. CONCLUSION: Analysis of the emergent trends suggests that economic
      activity, status and position possibly provide a better overall explanatory model
      than a purely biomedical approach.

PMID- 17234878
TI  - Modelling of municipal mortality due to haematological neoplasias in Spain.
AB  - OBJECTIVES: To study the geographical pattern of mortality caused by
      haematological tumours in Spain at the municipal level using three Bayesian
      models and to compare their goodness of fit. METHODS: The fitted Bayesian
      hierarchical models were: (1) the Besag York and Mollie (BYM) model; (2) a model
      based on zero-inflated Poisson (ZIP) distribution, which allowed a large number
      of event-free areas; and (3) a mixture of distributions that enabled
      discontinuities (jumps in the pattern) to be modelled. The three models allow
      smoothed relative risk maps to be obtained for the all countries. The goodness of
      fit was evaluated using the deviance information criteria. RESULTS: The three
      models yielded similar results. The ZIP model plotted a pattern almost identical
      with the BYM model. The goodness-of-fit criteria indicate that the mixture model
      is the one that best fits our data. Haematological tumours display a geographical
      pattern that could be partly explained by environmental determinants, as many of
      the highest-risk towns are located in heavily industrialised areas. CONCLUSIONS:
      The choice of one or another model has scant practical consequences. The pattern
      of distribution supports the hypothesis that differences in lifestyles,
      air/industrial pollution and migratory phenomena may determine the pattern of
      urban mortality due to these tumours.

PMID- 17234879
TI  - Altitude, latitude and sex ratio at birth in Iran.

PMID- 17234880
TI  - Genetic interaction screens advance in reverse.

PMID- 17234881
TI  - The t-complex-encoded guanine nucleotide exchange factor Fgd2 reveals that two
      opposing signaling pathways promote transmission ratio distortion in the mouse.
AB  - Transmission ratio distortion (TRD), the preferential inheritance of the t
      haplotype from t/+ males, is caused by the cooperative effect of four t-complex
      distorters (Tcd1-4) and the single t-complex responder (Tcr) on sperm motility.
      Here we show that Fgd2, encoding a Rho guanine nucleotide exchange factor, maps
      to the Tcd2 region. The t allele of Fgd2 is overexpressed in testis compared with
      wild type. A loss-of-function allele of Fgd2 generated by gene targeting reduces
      the transmission ratio of the t haplotype t(h49), directly demonstrating the role
      of Fgd2 as Distorter. Fgd2 identifies a second Rho G protein signaling pathway
      promoting TRD.

PMID- 17234882
TI  - The Spt6 SH2 domain binds Ser2-P RNAPII to direct Iws1-dependent mRNA splicing
      and export.
AB  - Spt6 promotes transcription elongation at many genes and functions as a histone
      H3 chaperone to alter chromatin structure during transcription. We show here that
      mammalian Spt6 binds Ser2-phosphorylated (Ser2P) RNA polymerase II (RNAPII)
      through a primitive SH2 domain, which recognizes phosphoserine rather than
      phosphotyrosine residues. Surprisingly, a point mutation in the Spt6 SH2 domain
      (R1358K) blocked binding to RNAPIIo without affecting transcription elongation
      rates in vitro. However, HIV-1 and c-myc RNAs formed in cells expressing the
      mutant Spt6 protein were longer than normal and contained splicing defects.
      Ectopic expression of the wild-type, but not mutant, Spt6 SH2 domain, caused bulk
      poly(A)+ RNAs to be retained in the nucleus, further suggesting a widespread role
      for Spt6 in mRNA processing or assembly of export-competent mRNP particles. We
      cloned the human Spt6-interacting protein, hIws1 (interacts with Spt6), and found
      that it associates with the nuclear RNA export factor, REF1/Aly. Depletion of
      endogenous hIws1 resulted in mRNA processing defects, lower levels of REF1/Aly at
      the c-myc gene, and nuclear retention of bulk HeLa poly(A)+ RNAs in vivo. Thus
      binding of Spt6 to Ser2-P RNAPII provides a cotranscriptional mechanism to
      recruit Iws1, REF1/Aly, and associated mRNA processing, surveillance, and export
      factors to responsive genes.

PMID- 17234883
TI  - IRES-mediated functional coupling of transcription and translation amplifies
      insulin receptor feedback.
AB  - It is generally accepted that the growth rate of an organism is modulated by the
      availability of nutrients. One common mechanism to control cellular growth is
      through the global down-regulation of cap-dependent translation by eIF4E-binding
      proteins (4E-BPs). Here, we report evidence for a novel mechanism that allows
      eukaryotes to coordinate and selectively couple transcription and translation of
      target genes in response to a nutrient and growth signaling cascade. The
      Drosophila insulin-like receptor (dINR) pathway incorporates 4E-BP resistant
      cellular internal ribosome entry site (IRES) containing mRNAs, to functionally
      couple transcriptional activation with differential translational control in a
      cell that is otherwise translationally repressed by 4E-BP. Although examples of
      cellular IRESs have been previously reported, their critical role mediating a key
      physiological response has not been well documented. Our studies reveal an
      integrated transcriptional and translational response mechanism specifically
      dependent on a cellular IRES that coordinates an essential physiological signal
      responsible for monitoring nutrient and cell growth conditions.

PMID- 17234884
TI  - The APC/C inhibitor, Emi1, is essential for prevention of rereplication.
AB  - Emi1 (early mitotic inhibitor) inhibits APC/C (anaphase-promoting
      complex/cyclosome) activity during S and G2 phases, and is believed to be
      required for proper mitotic entry. We report that Emi1 plays an essential
      function in cell proliferation by preventing rereplication. Rereplication seen
      after Emi1 depletion is due to premature activation of APC/C that results in
      destabilization of geminin and cyclin A, two proteins shown here to play
      redundant roles in preventing rereplication in mammalian cells. Geminin is known
      to inhibit the replication initiation factor Cdt1. The rereplication block by
      cyclin A is mediated through its association with S and G2/M cyclin-dependent
      kinases (Cdks), Cdk2 and Cdk1, suggesting that phosphorylation of proteins by
      cyclin A-Cdk is responsible for the block. Rereplication upon Emi1 depletion
      activates the DNA damage checkpoint pathways. These data suggest that Emi1 plays
      a critical role in preserving genome integrity by blocking rereplication,
      revealing a previously unrecognized function of this inhibitor of APC/C.

PMID- 17234885
TI  - Evolutionary constraints on chaperone-mediated folding provide an antiviral
      approach refractory to development of drug resistance.
AB  - The genome diversity of RNA viruses allows for rapid adaptation to a wide variety
      of adverse conditions. Accordingly, viruses can escape inhibition by most
      antiviral compounds targeting either viral or host factors. Here we exploited the
      capacity of RNA viruses for rapid adaptation to explore the evolutionary
      constraints of chaperone-mediated protein folding. We hypothesized that
      inhibiting a host molecular chaperone required for folding of a viral protein
      would force the virus to evolve an alternate folding strategy. We identified the
      chaperone Hsp90 as an essential factor for folding and maturation of picornavirus
      capsid proteins. Pharmacological inhibition of Hsp90 impaired the replication of
      poliovirus, rhinovirus, and coxsackievirus in cell culture. Strikingly, anti
      Hsp90 treatment did not yield drug-resistant viruses, suggesting that the
      complexity of capsid folding precludes the emergence of alternate folding
      pathways. These results reveal tight evolutionary constraints on chaperone
      mediated protein folding, which may be exploited for viral inhibition in vivo.
      Indeed, Hsp90 inhibitors drastically reduced poliovirus replication in infected
      animals without the emergence of drug-resistant escape mutants. We propose that
      targeting folding of viral proteins may provide a general antiviral strategy that
      is refractory to development of drug resistance.

PMID- 17234887
TI  - Multiple small RNAs act additively to integrate sensory information and control
      quorum sensing in Vibrio harveyi.
AB  - Quorum sensing is a cell-cell communication mechanism that bacteria use to
      collectively regulate gene expression and, at a higher level, to coordinate group
      behavior. In the bioluminescent marine bacterium Vibrio harveyi, sensory
      information from three independent quorum-sensing systems converges on the shared
      response regulator LuxO. When LuxO is phosphorylated, it activates the expression
      of a putative repressor that destabilizes the mRNA encoding the master quorum
      sensing transcriptional regulator LuxR. In the closely related species Vibrio
      cholerae, this repressor was revealed to be the RNA chaperone Hfq together with
      four small regulatory RNAs (sRNAs) called Qrr1-4 (quorum regulatory RNA). Here,
      we identify five Qrr sRNAs that control quorum sensing in V. harveyi. Mutational
      analysis reveals that only four of the five Qrrs are required for destabilization
      of the luxR mRNA. Surprisingly, unlike in V. cholerae where the sRNAs act
      redundantly, in V. harveyi, the Qrr sRNAs function additively to control quorum
      sensing. This latter mechanism produces a gradient of LuxR that, in turn, enables
      differential regulation of quorum-sensing target genes. Other regulators appear
      to be involved in control of V. harveyi qrr expression, allowing the integration
      of additional sensory information into the regulation of quorum-sensing gene
      expression.

PMID- 17234886
TI  - Telomerase abrogation dramatically accelerates TRF2-induced epithelial
      carcinogenesis.
AB  - TRF2 is a telomere-binding protein with roles in telomere protection and telomere
      length regulation. The fact that TRF2 is up-regulated in some human tumors
      suggests a role of TRF2 in cancer. Mice that overexpress TRF2 in the skin, K5TRF2
      mice, show critically short telomeres and are susceptible to UV-induced
      carcinogenesis as a result of deregulated XPF/ERCC1 activity, a nuclease involved
      in UV damage repair. Here we demonstrate that, when in combination with
      telomerase deficiency, TRF2 acts as a very potent oncogene in vivo. In
      particular, we show that telomerase deficiency dramatically accelerates TRF2
      induced epithelial carcinogenesis in K5TRF2/Terc-/- mice, coinciding with
      increased chromosomal instability and DNA damage. Telomere recombination is also
      increased in these mice, suggesting that TRF2 favors the activation of
      alternative telomere maintenance mechanisms. Together, these results demonstrate
      that TRF2 increased expression is a potent oncogenic event that along with
      telomerase deficiency accelerates carcinogenesis, coincidental with a
      derepression of telomere recombination. These results are of particular relevance
      given that TRF2 is up-regulated in some human cancers. Furthermore, these data
      suggest that telomerase inhibition might not be effective to cease the growth of
      TRF2-overexpressing tumors.

PMID- 17234889
TI  - IL-1beta inhibits intestinal smooth muscle proliferation in an organ culture
      system: involvement of COX-2 and iNOS induction in muscularis resident
      macrophages.
AB  - Intestinal inflammation causes hyperplasia of smooth muscle that leads to
      thickening of the smooth muscle layer, resulting in dysmotility. IL-1beta is a
      proinflammatory cytokine that plays a central role in intestinal inflammation. In
      this study, to evaluate the effect of IL-1beta on proliferation of ileal smooth
      muscle cells in vivo, we utilized an organ culture system. When rat ileal smooth
      muscle tissue was cultured under serum-free conditions for 3 days, most smooth
      muscle cells maintained their arrangement and kept their contractile phenotype.
      When 10% FBS was added, an increased number of smooth muscle cells per unit area
      was observed. Moreover, immunohistochemical staining for PCNA demonstrated that
      FBS induced proliferation of smooth muscle cells. IL-1beta inhibited the
      proliferative effect of FBS. Furthermore, IL-1beta upregulated inducible nitric
      oxide (NO) synthase and cyclooxygenase-2 mRNA and protein and thus stimulated NO
      and PGE(2) productions. Moreover, exogenously applied NO and PGE(2) inhibited the
      increase of bromodeoxyuridine-positive cells stimulated with FBS. Immunostaining
      revealed that the majority of cyclooxygenase-2 and inducible NO synthase was
      located in the dense network of macrophages resident in the muscularis, which
      were immunoreactive to ED2. Based on these findings, IL-1beta acts as an anti
      proliferative mediator, which acts indirectly through the production of PGE(2)
      and NO from resident macrophage within ileal smooth muscle tissue.

PMID- 17234888
TI  - Cyclic AMP-dependent protein kinase and Epac mediate cyclic AMP responses in
      pancreatic acini.
AB  - The pancreatic acinar cell has several phenotypic responses to cAMP agonists. At
      physiological concentrations of the muscarinic agonist carbachol (1 microM) or
      the CCK analog caerulein (100 pM), ligands that increase cytosolic Ca(2+), cAMP
      acts synergistically to enhance secretion. Supraphysiological concentrations of
      carbachol (1 mM) or caerulein (100 nM) suppress secretion and cause intracellular
      zymogen activation; cAMP enhances both zymogen activation and reverses the
      suppression of secretion. In addition to stimulating cAMP-dependent protein
      kinase (PKA), recent studies using cAMP analogs that lack a PKA response have
      shown that cAMP can also act through the cAMP-binding protein, Epac (exchange
      protein directly activated by cyclic AMP). The roles of PKA and Epac in cAMP
      responses were examined in isolated pancreatic acini. The activation of both cAMP
      dependent pathways or the selective activation of Epac was found to enhance
      amylase secretion induced by physiological and supraphysiological concentrations
      of the muscarinic agonist carbachol. Similarly, activation of both PKA or the
      specific activation of Epac enhanced carbachol-induced activation of trypsinogen
      and chymotrypsinogen. Disorganization of the apical actin cytoskeleton has been
      linked to the decreased secretion observed with supraphysiological concentrations
      of carbachol and caerulein. Although stimulation of PKA and Epac or Epac alone
      could largely overcome the decreased secretion observed with either
      supraphysiological carbachol or caerulein, stimulation of cAMP pathways did not
      reduce the disorganization of the apical cytoskeleton. These studies demonstrate
      that PKA and Epac pathways are coupled to both secretion and zymogen activation
      in the pancreatic acinar cell.

PMID- 17234890
TI  - The impact of continuous positive airway pressure on the lower esophageal
      sphincter.
AB  - The lower esophageal sphincter (LES) is the primary barrier to gastroesophageal
      reflux. Reflux is associated with periods of LES relaxation, as occurs during
      swallowing. Continuous positive airway pressure (CPAP) has been shown to reduce
      reflux in individuals with and without sleep apnea, by an unknown mechanism. The
      aim of this study was to determine the effect of CPAP on swallow-induced LES
      relaxation. Measurements were made in 10 healthy, awake, supine individuals.
      Esophageal (Pes), LES (Ples), gastric (Pg), and barrier pressure to reflux (Pb =
      Ples - Pg) were recorded using a sleeve catheter during five swallows of 5 ml of
      water. This was repeated at four levels of CPAP (0, 5, 10, and 15 cmH(2)O).
      Pressures were measured during quiet breathing and during the LES relaxation
      associated with a swallow. Duration of LES relaxation was also recorded. During
      quiet breathing, CPAP significantly increased end-expiratory Pes, Ples, Pg, and
      Pb (P < 0.05). The increase in Pb was due to a disproportionate increase in Ples
      compared with Pg (P < 0.05). During a swallow, CPAP increased nadir Ples, Pg, and
      Pb and decreased the duration of LES relaxation (4.1 s with 0-cmH(2)O CPAP to 1.6
      s on 15-cmH(2)O CPAP, P < 0.001). Pb increased with CPAP by virtue of a
      disproportionate increase in Ples compared with Pg. This may be due to either
      reflex activation of LES smooth muscle, or nonspecific transmission of pressure
      to the LES. The findings suggest CPAP may make the LES less susceptible to reflux
      by increasing Pb and decreasing the duration of LES relaxation.

PMID- 17234891
TI  - Distinct modulation of Kv1.2 channel gating by wild type, but not open form, of
      syntaxin-1A.
AB  - SNARE proteins, syntaxin-1A (Syn-1A) and SNAP-25, inhibit delayed rectifier K(+)
      channels, K(v)1.1 and K(v)2.1, in secretory cells. We showed previously that the
      mutant open conformation of Syn-1A (Syn-1A L165A/E166A) inhibits K(v)2.1 channels
      more optimally than wild-type Syn-1A. In this report we examined whether Syn-1A
      in its wild-type and open conformations would exhibit similar differential
      actions on the gating of K(v)1.2, a major delayed rectifier K(+) channel in
      nonsecretory smooth muscle cells and some neuronal tissues. In coexpression and
      acute dialysis studies, wild-type Syn-1A inhibited K(v)1.2 current magnitude. Of
      interest, wild-type Syn-1A caused a right shift in the activation curves of
      K(v)1.2 without affecting its steady-state availability, an inhibition profile
      opposite to its effects on K(v)2.1 (steady-state availability reduction without
      changes in voltage dependence of activation). Also, although both wild-type and
      open-form Syn-1A bound equally well to K(v)1.2 in an expression system, open-form
      Syn-1A failed to reduce K(v)1.2 current magnitude or affect its gating. This is
      in contrast to the reported more potent effect of open-form Syn-1A on K(v)2.1
      channels in secretory cells. This finding together with the absence of Munc18
      and/or 13-1 in smooth muscles suggested that a change to an open conformation Syn
      1A, normally facilitated by Munc18/13-1, is not required in nonsecretory smooth
      muscle cells. Taken together with previous reports, our results demonstrate the
      multiplicity of gating inhibition of different K(v) channels by Syn-1A and is
      compatible with versatility of Syn-1A modulation of repolarization in various
      secretory and nonsecretory (smooth muscle) cell types.

PMID- 17234892
TI  - Multiple routes of chemosensitivity to free fatty acids in humans.
AB  - Selected free fatty acids (FFAs) are documented effective somatosensory and
      olfactory stimuli whereas gustatory effects are less well established. This study
      examined orthonasal olfactory, retronasal olfactory, nasal irritancy, oral
      irritancy, gustatory, and multimodal threshold sensitivity to linoleic, oleic,
      and stearic acids. Sensitivity to oxidized linoleic acid was also determined.
      Detection thresholds were obtained using a three-alternative, forced-choice,
      ascending concentration presentation procedure. Participants included 22 healthy,
      physically fit adults sensitive to 6-n-propylthiouracil. Measurable thresholds
      were obtained for all FFAs tested and in 96% of the trials. Ceiling effects were
      observed in the remaining trials. Greater sensitivity was observed for multimodal
      stimulation and lower sensitivity for retronasal stimulation. There were no
      statistically significant correlations for linoleic acid thresholds between
      different modalities, suggesting that each route of stimulation contributes
      independently to fat perception. In summary, 18-carbon FFAs of varying saturation
      are detected by multiple sensory systems in humans.

PMID- 17234893
TI  - Treatment with BX471, a CC chemokine receptor 1 antagonist, attenuates systemic
      inflammatory response during sepsis.
AB  - Sepsis is a complex clinical syndrome resulting from a harmful host inflammatory
      response to infection. Chemokines and their receptors play a key role in the
      pathogenesis of sepsis. BX471 is a potent nonpeptide CC chemokine receptor-1
      (CCR1) antagonist in both human and mouse. The aim of the present study was to
      evaluate the effect of prophylactic and therapeutic treatment with BX471 on cecal
      ligation and puncture-induced sepsis in the mouse and to investigate the
      underlying mechanisms. In sepsis induced by cecal ligation and puncture,
      treatment with BX471 significantly protected mice against lung and liver injury
      by attenuating MPO activity, an indicator of neutrophil recruitment in lungs and
      livers and attenuating lung and liver morphological changes in histological
      sections. Blocking CCR1 by BX471 also downregulated ICAM-1, P-selectin, and E
      selectin expression at mRNA and protein levels in lungs and livers compared with
      placebo-treated groups. These findings suggest that blockage of CCR1 by specific
      antagonist may represent a promising strategy to prevent disease progression in
      sepsis.

PMID- 17234894
TI  - Albumin synthesis in preterm infants on the first day of life studied with [1
      13C]leucine.
AB  - Albumin is the major binding protein in the human neonate. Low production of
      albumin will lower its transport and binding capacity. This is especially
      important in preterm infants, in whom albumin binds to potentially toxic products
      such as bilirubin and antibiotics. To study the metabolism of plasma albumin in
      preterm infants, we administered a 24-h constant infusion of [1-(13)C]leucine to
      24 very low birth weight (VLBW) infants (28.4 +/- 0.4 wk, 1,080 +/- 75 g) on the
      first day of life. The caloric intake consisted of glucose only, and therefore
      amino acids for albumin synthesis were derived from proteolysis. The fractional
      synthesis rate (FSR) of plasma albumin was 13.9 +/- 1.5%/day, and the absolute
      synthesis rate was 148 +/- 17 mg x kg(-1) x day(-1). Synthesis rates were
      significantly lower (P<0.03) in infants showing intrauterine growth retardation.
      Albumin synthesis increased with increasing SD scores for gestation and weight
      (P<0.05). The FSR of albumin tended to increase by 37% after administration of
      antenatal corticosteroids to improve postnatal lung function (P=0.09). We
      conclude that liver synthetic capacity is well developed in VLBW infants and that
      prenatal corticosteroids tend to increase albumin synthesis. Decreased weight
      gain rates in utero have effects on protein synthesis postnatally.

PMID- 17234895
TI  - Adequate oral threonine is critical for mucin production and gut function in
      neonatal piglets.
AB  - In previous experiments, we found that the threonine requirement of neonatal
      piglets fed parenterally was 40% of that when fed intragastrically; we
      hypothesized that much of the oral supply of threonine is being used for mucin
      production. To investigate this hypothesis, intragastrically fed 2-day-old
      piglets were fed one of three treatments for 8 days: 1) a threonine-adequate diet
      (IG-A; 0.6 g threonine.kg(-1).day(-1) fed intragastrically); 2) a threonine
      deficient diet (IG-D; 0.1 g threonine.kg(-1).day(-1) fed intragastrically); or 3)
      a threonine-deficient diet with adequate threonine delivered parenterally (IV-A;
      0.5 g threonine.kg(-1).day(-1) fed parenterally plus 0.1 g threonine.kg(-1).day(
      1) fed intragastrically). IG-D piglets experienced higher nitrogen excretion,
      higher plasma urea, and lower plasma threonine concentrations versus both of the
      other groups (P < 0.05), indicating profound threonine deficiency. Mucosal mass
      and total crude mucin content were lower in the colons of IG-D pigs (P < 0.05).
      Histopathological analysis showed lower numbers of acidic mucin-producing goblet
      cells in the duodenum and ileum of IG-D pigs. In IG-D pigs, acidic mucin subtypes
      were lower in the small intestine but higher in the colon, which corresponded
      with persistent diarrhea. The parenteral supply of threonine was adequate to
      maintain most outcome parameters, although IV-A pigs did have smaller colonic
      goblet cells with more acidic mucins compared with IG-A pigs. Overall, our
      results suggest that adequate dietary threonine was critical in the production of
      mucus and that a parenteral threonine supply can ameliorate most of the symptoms
      of oral threonine deficiency.

PMID- 17234896
TI  - Loss of the high-affinity pentamidine transporter is responsible for high levels
      of cross-resistance between arsenical and diamidine drugs in African
      trypanosomes.
AB  - Treatment of many infectious diseases is under threat from drug resistance.
      Understanding the mechanisms of resistance is as high a priority as the
      development of new drugs. We have investigated the basis for cross-resistance
      between the diamidine and melaminophenyl arsenical classes of drugs in African
      trypanosomes. We induced high levels of pentamidine resistance in a line without
      the tbat1 gene that encodes the P2 transporter previously implicated in drug
      uptake. We isolated independent clones that displayed very considerable cross
      resistance with melarsen oxide but not phenylarsine oxide and reduced uptake of
      [(3)H]pentamidine. In particular, the high-affinity pentamidine transport (HAPT1)
      activity was absent in the pentamidine-adapted lines, whereas the low affinity
      pentamidine transport (LAPT1) activity was unchanged. The parental tbat1(-/-)
      line was sensitive to lysis by melarsen oxide, and this process was inhibited by
      low concentrations of pentamidine, indicating the involvement of HAPT1. This
      pentamidine-inhibitable lysis was absent in the adapted line KO-B48. Likewise,
      uptake of the fluorescent diamidine 4',6-diamidino-2-phenylindole dihydrochloride
      was much delayed in live KO-B48 cells and insensitive to competition with up to
      10 muM pentamidine. No overexpression of the Trypanosoma brucei brucei ATP
      binding cassette transporter TbMRPA could be detected in KO-B48. We also show
      that a laboratory line of Trypanosoma brucei gambiense, adapted to high levels of
      resistance for the melaminophenyl arsenical drug melarsamine hydrochloride
      (Cymelarsan), had similarly lost TbAT1 and HAPT1 activity while retaining LAPT1
      activity. It seems therefore that selection for resistance to either pentamidine
      or arsenical drugs can result in a similar phenotype of reduced drug
      accumulation, explaining the occurrence of cross-resistance.

PMID- 17234897
TI  - Function of both sinusoidal and canalicular transporters controls the
      concentration of organic anions within hepatocytes.
AB  - We hypothesized that the function of both sinusoidal and canalicular transporters
      importantly controls the concentrations of organic anions within normal
      hepatocytes. Consequently, we investigated how acute transport regulation of the
      sinusoidal organic anion transporting polypeptides (Oatps) and the canalicular
      multidrug resistance associated protein 2 (Mrp(2)) determines the hepatic
      concentrations of the organic anion gadolinium benzyloxypropionictetraacetate
      (BOPTA) in rat livers. Livers were perfused with labeled BOPTA in different
      experimental settings that modify the function of Oatps and Mrp(2) through the
      protein kinase C (PKC) pathway. Intrahepatic concentrations were continuously
      measured with a gamma probe placed above rat livers. Labeled BOPTA was also
      measured in perfusate and bile. We showed that when the function of Oatps and
      Mrp(2) is modified in such a way that BOPTA entry and exit are similarly
      decreased, concentrations of organic anions within hepatocytes remain unaltered.
      When exit through Mrp(2) is abolished, hepatic concentrations are high if entry
      through Oatps is only slightly decreased (livers without Mrp(2) expression) or
      low if BOPTA uptake is more importantly decreased (livers perfused with a PKC
      activator). These results highlight that the function of both sinusoidal and
      canalicular transporters is important to determine the concentration of organic
      anions within hepatocytes.

PMID- 17234898
TI  - In vivo regulation of Homer1a expression in the striatum by cocaine.
AB  - The glutamate receptor adaptor protein Homer is concentrated in the postsynaptic
      density of excitatory synapses and is critical for normal operation of synaptic
      transmission. In this study, we investigated the responsiveness of Homer family
      proteins to dopamine stimulation with the psychostimulant cocaine in rat striatal
      neurons both in vivo and in vitro. We found that a single dose of cocaine
      specifically induced a rapid and transient increase in protein levels of the
      Homer1a, but not Homer1b/c and Homer2a/b, isoforms in the striatum. This
      selective Homer1a induction was mediated primarily through activation of dopamine
      D1, but not D2, receptors. Both protein kinase A and Ca(2+)/calmodulin-dependent
      protein kinases are important for mediating the cocaine stimulation of Homer1a
      expression. At the transcriptional level, cAMP response element-binding protein
      serves as a prime transcription factor transmitting the signals derived from D1
      receptors and associative pathways to the CaCRE sites within the Homer1a
      promoter. From a functional perspective, non-cross-linking Homer1a, once induced,
      competed with the cross-linking isoforms of Homer proteins (Homer1b/c and
      Homer2a/b) to uncouple the connection of group I metabotropic glutamate receptors
      (mGluRs) with inositol-1,4,5-triphosphate receptors. These results indicate that
      cocaine possesses the ability to stimulate Homer1a expression in striatal neurons
      through a specific synapse-to-nucleus pathway. Moreover, inducible Homer1a
      expression may represent a transcription-dependent mechanism underlying the
      dynamic regulation of submembranous macromolecular complex formation between
      group I mGluRs and their anchoring proteins.

PMID- 17234899
TI  - Trace amine-associated receptor 1 is a modulator of the dopamine transporter.
AB  - Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor
      activated by a broad range of monoamines and amphetamine-related
      psychostimulants. Recent studies demonstrated wide distribution of TAAR1 in
      brain, coexpression of TAAR1 with dopamine transporter (DAT) in a subset of
      dopamine neurons in both mouse and rhesus monkey substantia nigra, and monoamine
      transporter-modulated activation. This study explored whether TAAR1 could
      influence DAT-mediated dopamine uptake and efflux. Rhesus monkey TAAR1 expressed
      with DAT in human embryonic kidney 293 cells was dose-dependently activated by
      dopamine or (+)-methamphetamine. This activation resulted in large cAMP increases
      and a transient reduction in [3H]dopamine accumulation within the cells, which
      was similar to the effect of dopamine D1 receptor (D1) or forskolin treatment. In
      addition, TAAR1 effects on dopamine uptake could be blocked by a protein kinase A
      or protein kinase C (PKC) inhibitor. [3H]Dopamine efflux assays performed in
      Dulbecco's modified Eagle's medium displayed a TAAR1-dependent spontaneous
      [3H]dopamine efflux that was dose-dependently augmented by dopamine or (+)
      methamphetamine and that was blocked by either methylphenidate or a PKC
      inhibitor. DAT cells in Krebs-HEPES buffer had an apparent spontaneous
      [3H]dopamine loss, but it could not be blocked by either methylphenidate or a PKC
      inhibitor. Taken together, this study provides evidence that TAAR1 is involved in
      functional regulation of DAT and suggests that TAAR1 is a potentially important
      target for therapeutics for methamphetamine addiction.

PMID- 17234900
TI  - Rhesus monkey trace amine-associated receptor 1 signaling: enhancement by
      monoamine transporters and attenuation by the D2 autoreceptor in vitro.
AB  - Trace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor that
      directly responds to endogenous monoamines as well as amphetamine-related
      psychostimulants, including methamphetamine. In the present study, we demonstrate
      TAAR1 mRNA and protein expression in rhesus monkey brain regions associated with
      monoaminergic systems, variable cellular distribution of TAAR1 in rhesus monkey
      brain, and TAAR1 coexpression with the dopamine transporter (DAT) in a subset of
      dopamine neurons in both rhesus monkey and mouse substantia nigra. On this basis,
      we evaluated rhesus monkey TAAR1 activation by different compounds and its
      functional relation with monoamine transporters and the dopamine D2 receptor (D2)
      short isoform (D2s) autoreceptor in vitro using a cAMP response element
      luciferase assay. TAAR1 activation by monoamines and amphetamine-related
      compounds was greatly enhanced by coexpression of dopamine, norepinephrine, or
      serotonin transporters, and the activation enhancement was blocked by monoamine
      transporter inhibitors. This enhancement did not occur in control experiments in
      which the dopamine D1 receptor (D1) was substituted for TAAR1. Furthermore,
      activation of TAAR1 by dopamine was completely inhibited by D2s when coexpressed
      with TAAR1, and this inhibition was blocked by the D2 antagonist raclopride.
      Last, dopamine activation of TAAR1 could induce c-FOS-luciferase expression but
      only in the presence of DAT, whereas dopamine activation of D1 resulted in
      equivalent c-FOS expression in the presence or absence of DAT. Together, these
      data reveal a broad agonist spectrum for TAAR1, a functional relation of TAAR1
      with monoamine transporters and D2s, and a mechanism by which D2 receptor drugs
      can influence brain monoaminergic function and have efficacy through affecting
      TAAR1 signaling.

PMID- 17234901
TI  - Overweight, obesity, and incident asthma: a meta-analysis of prospective
      epidemiologic studies.
AB  - RATIONALE: Although obesity has been implicated as an asthma risk factor, there
      is heterogeneity in the published literature regarding its role in asthma
      incidence, particularly in men. OBJECTIVES: To quantify the relationship between
      categories of body mass index (BMI) and incident asthma in adults and to evaluate
      the impact of sex on this relationship. METHODS: Online bibliographic databases
      were searched for prospective studies evaluating BMI and incident asthma in
      adults. Independent observers extracted data regarding annualized asthma
      incidence from studies meeting predetermined criteria, within defined categories
      of normal weight (BMI < 25), overweight (BMI, 25-29.9), and obesity (BMI >or=
      30). Data were analyzed by inverse-variance-weighted, random-effects meta
      analysis. Stratified analysis between BMI categories and within sex was
      performed. RESULTS: Seven studies (n=333,102 subjects) met inclusion criteria.
      Compared with normal weight, overweight and obesity (BMI >or= 25) conferred
      increased odds of incident asthma, with an odds ratio (OR) of 1.51 (95%
      confidence interval [CI], 1.27-1.80). A dose-response effect of elevated BMI on
      asthma incidence was observed; the OR for incident asthma for normal-weight
      versus overweight subjects was 1.38 (95% CI, 1.17-1.62) and was further elevated
      for normal weight versus obesity (OR, 1.92; 95% CI, 1.43-2.59; p<0.0001 for the
      trend). A similar increase in the OR of incident asthma due to overweight and
      obesity was observed in men (OR, 1.46; 95% CI, 1.05-2.02) and women (OR, 1.68;
      95% CI, 1.45-1.94; p=0.232 for the comparison). CONCLUSIONS: Overweight and
      obesity are associated with a dose-dependent increase in the odds of incident
      asthma in men and women, suggesting asthma incidence could be reduced by
      interventions targeting overweight and obesity.

PMID- 17234902
TI  - Association between pulmonary function and sputum biomarkers in cystic fibrosis.
AB  - RATIONALE: Sputum biomarkers of infection and inflammation are noninvasive
      measures that enable quantification of the complex pathophysiology of cystic
      fibrosis (CF) lung disease. Validation of these biomarkers as correlates of
      disease severity is a key step for their application. OBJECTIVES: We constructed
      a large database from four multicenter studies to quantify the strength of
      association between expectorated sputum biomarkers and FEV(1.) METHODS: FEV(1)
      (range, 25-120% predicted) and quantitative data on expectorated sputum
      biomarkers including free neutrophil elastase, IL-8, neutrophils, Pseudomonas
      aeruginosa, and Staphylococcus aureus were obtained from 269 participants (ages,
      9-54 years) from 33 centers. Cross-sectional and longitudinal statistical
      analyses were performed to estimate associations between the markers and FEV(1),
      including the use of multivariable analyses. RESULTS: Elastase was negatively
      correlated with FEV(1) (correlation [r] = -0.35; 95% confidence interval [CI]: 
      0.46, -0.22). On average, patients with CF who differed in their elastase
      measurements by 0.5 log differed in their FEV(1) values by -7.3% (95% CI: -9.7, 
      4.6). Neutrophil counts and IL-8 were also each negatively correlated. In a
      multivariable regression, elastase and neutrophil counts were able to explain the
      majority of variation in FEV(1). Elastase was further shown to have a significant
      longitudinal association with FEV(1), specifically a -2.9% decline in FEV(1) (95%
      CI: -5.0, -0.9) per 1-log increase in elastase. Although correlated with FEV(1),
      bacterial densities were unable to explain clinically meaningful differences in
      FEV(1) within and across patients. CONCLUSIONS: These data support the role of
      sputum biomarkers as correlates of disease severity in a diverse CF population.

PMID- 17234903
TI  - Herpes simplex virus lung infection in patients undergoing prolonged mechanical
      ventilation.
AB  - RATIONALE: It is not known whether the isolation of herpes simplex virus (HSV)
      from lower respiratory tract samples of nonimmunocompromised ventilated patients
      corresponds to bronchial contamination from the mouth and/or throat, local
      tracheobronchial excretion of HSV, or true HSV lung involvement
      (bronchopneumonitis) with its own morbidity/mortality. OBJECTIVES: This
      prospective, single-center, observational study was conducted to define the
      frequency, risk factors, and relevance of HSV bronchopneumonitis. METHODS: All
      consecutive nonimmunocompromised patients receiving mechanical ventilation for 5
      days or more were evaluated. Bronchoalveolar lavage, oropharyngeal swabs, and
      bronchial biopsies (presence of macroscopic bronchial lesions) were obtained for
      all who deteriorated clinically with suspected lung infection. HSV
      bronchopneumonitis was defined as this deterioration, associated with HSV in
      bronchoalveolar lavage and HSV-specific nuclear inclusions in cells recovered
      during lavage or bronchial biopsies. MEASUREMENTS AND MAIN RESULTS: HSV
      bronchopneumonitis was diagnosed in 42 (21%) of the 201 patients who deteriorated
      clinically, with a mean mechanical ventilation duration before diagnosis of 14 +/
      6 days. Risk factors associated with HSV bronchopneumonitis were oral-labial
      lesions, HSV in the throat, and macroscopic bronchial lesions seen during
      bronchoscopy. Patients with HSV bronchopneumonitis were comparable to those
      without at admission, but their courses were more complicated, with longer
      duration of mechanical ventilation and intensive care unit stays. CONCLUSIONS:
      HSV bronchopneumonitis is common in nonimmunocompromised patients with prolonged
      mechanical ventilation, is associated with HSV reactivation or infection of the
      mouth and/or throat, and seems to be associated with poorer outcome.

PMID- 17234904
TI  - Early detection of chronic pulmonary allograft dysfunction by exhaled biomarkers.
AB  - RATIONALE: Early detection of bronchiolitis obliterans syndrome (BOS) is
      important because therapies are more likely to be effective if employed early in
      the disease process. OBJECTIVES: To compare the performance of exhaled NO and CO
      (which reflect airway inflammation) and the slope of the alveolar plateau for
      helium (which reflects heterogeneity of ventilation distribution) for detection
      of BOS stages 0-p and 1. METHODS: Recipients of bilateral (n=64) and single (n=1)
      lung grafts were prospectively monitored for 1,249 days; the helium slope was
      derived from single-breath washouts and exhaled NO and CO were measured by
      chemiluminescence on 933 occasions. MEASUREMENTS AND MAIN RESULTS: At the end of
      follow-up, 9 patients were in stage 0-p and 16 patients were in BOS stage 1 or
      higher; 21 patients had at least one measurement made in BOS stage 0-p. All
      markers increased in BOS stage 0-p, but only the helium slope increased in BOS
      stage 1. The helium slope had better sensitivity for detection of stages 0-p and
      1 than either exhaled NO or CO, but considering exhaled NO and CO together
      improved their sensitivity; the best sensitivity was found with the three markers
      in combination. The biomarkers had high negative predictive values, but low
      specificity and positive predictive values. CONCLUSIONS: After lung
      transplantation, (1) the helium slope and exhaled NO, but also exhaled CO,
      increase in BOS stage 0-p, (2) the helium slope has better sensitivity than
      exhaled NO and CO for the detection of BOS stages 0-p and 1, and (3) exhaled
      biomarkers have high negative predictive values, but low specificity and positive
      predictive values.

PMID- 17234905
TI  - High level of burnout in intensivists: prevalence and associated factors.
AB  - RATIONALE: Professional burnout is a psychological syndrome arising in response
      to chronic interpersonal stressors on the job. There is the perception that
      intensivists are particularly exposed to stress because lives are literally in
      their hands. OBJECTIVE: To evaluate the prevalence and associated factors
      (patients or organization) of burnout among physicians working in intensive care
      units (ICUs) (including interns, residents, fellows, and attending physicians).
      METHODS: A 1-day national survey was conducted in adult ICUs in French public
      hospitals. MEASUREMENTS: The level of burnout was evaluated on the basis of the
      Maslach Burnout Inventory (MBI). MAIN RESULTS: A total of 189 ICUs participated
      and 978 surveys were returned (82.3% response rate). A high level of burnout was
      identified in 46.5% of the respondents. Ordinal logistic regression showed that
      female sex (odds ratio, 1.58; 95% confidence interval, 1.09 to 2.30) was
      independently associated with a higher MBI score. Whereas no factor related to
      the severity of illness of patients was retained by the model, organizational
      factors were strongly associated with a higher MBI score. Workload (the number of
      night shifts per month, a long period of time from the last nonworking week,
      night shift the day before the survey) and impaired relationships (such as
      conflict with another colleague intensivist, and/or with a nurse) were the
      variables independently associated with a higher MBI score. In contrast, the
      quality of the relationships with chief nurses and nurses was associated with a
      lower MBI score. CONCLUSIONS: Approximately one-half of the intensivists
      presented a high level of burnout. Organizational factors, but not factors
      related to the patients, appeared to be associated with burnout.

PMID- 17234906
TI  - Selective NOD1 agonists cause shock and organ injury/dysfunction in vivo.
AB  - RATIONALE: NLRs (nucleotide oligomerisation domain [NOD] proteins containing a
      leucine-rich repeat) are cytosolic pattern recognition receptors. NOD1 senses
      diaminopimelic acid-containing peptidoglycan present in gram-negative bacteria,
      whereas NOD2 senses the muramyl dipeptide (MDP) present in most organisms.
      Bacteria are the most common cause of septic shock, which is characterized
      clinically by hypotension resistant to vasopressor agents. In animal models, gram
      negative septic shock is mimicked by lipopolysaccharide (LPS), which signals
      through Toll-like receptor 4 (TLR4) and its adaptor MyD88. The role of NLRs in
      the pathophysiology of septic shock is not known. OBJECTIVES: To compare the
      effects of selective NOD1 agonists with LPS in vivo. METHODS: Vascular smooth
      muscle cells or whole aortas from wild-type or genetically modified mice were
      stimulated in vitro with agonists of NOD1 (FK565) or NOD2 (MDP). Vasoconstriction
      was measured using wire myography. Nitric oxide (NO) formation was measured using
      Griess reaction and NO synthase-II protein by Western blotting. In vivo, blood
      pressure, heart rate, and urine output were measured in sham-, LPS-, or FK565
      treated animals. Biomarkers of end-organ injury, coagulation activation, NO, and
      cytokines were measured in plasma. MAIN RESULTS: FK565, but not MDP, induced NO
      synthase-II protein/activity in vascular smooth muscle and vascular
      hyporeactivity to pressor agents. FK565 had no effect on vessels from NOD1(-/-)
      mice, but was active in vessels from TLR4(-/-), TLR2(-/-), or MyD88(-/-) mice.
      FK565 induced hypotension, increased heart rate, and caused multiple (renal,
      liver) injury and dysfunction in vivo. CONCLUSIONS: Activation of NOD1 induces
      shock and multiple organ injury/dysfunction.

PMID- 17234908
TI  - Spoilt for choice?

PMID- 17234909
TI  - C-reactive protein: does it predict mortality?

PMID- 17234910
TI  - Anti-tumor necrosis factor-alpha in asthma.

PMID- 17234911
TI  - Against misleading predictions for severe community-acquired pneumonia.

PMID- 17234912
TI  - A pressure increase due to hydrostatic pressure of perfluorocarbon is not obvious
      as sensed by pulmonary stretch receptors.

PMID- 17234913
TI  - Avoiding bias in the annualized rate of change of FEV1.

PMID- 17234915
TI  - Integration of TGF-beta and Ras/MAPK signaling through p53 phosphorylation.
AB  - During development and tissue homeostasis, cells must integrate different
      signals. We investigated how cell behavior is controlled by the combined activity
      of transforming growth factor-beta (TGF-beta) and receptor tyrosine kinase (RTK)
      signaling, whose integration mechanism is unknown. We find that RTK/Ras/MAPK
      (mitogen-activated protein kinase) activity induces p53 N-terminal
      phosphorylation, enabling the interaction of p53 with the TGF-beta-activated
      Smads. This mechanism confines mesoderm specification in Xenopus embryos and
      promotes TGF-beta cytostasis in human cells. These data indicate a mechanism to
      allow extracellular cues to specify the TGF-beta gene-expression program.

PMID- 17234914
TI  - Staphylococcus aureus Panton-Valentine leukocidin causes necrotizing pneumonia.
AB  - The Staphylococcus aureus Panton-Valentine leukocidin (PVL) is a pore-forming
      toxin secreted by strains epidemiologically associated with the current outbreak
      of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and
      with the often-lethal necrotizing pneumonia. To investigate the role of PVL in
      pulmonary disease, we tested the pathogenicity of clinical isolates, isogenic PVL
      negative and PVL-positive S. aureus strains, as well as purified PVL, in a mouse
      acute pneumonia model. Here we show that PVL is sufficient to cause pneumonia and
      that the expression of this leukotoxin induces global changes in transcriptional
      levels of genes encoding secreted and cell wall-anchored staphylococcal proteins,
      including the lung inflammatory factor staphylococcal protein A (Spa).

PMID- 17234917
TI  - Source it out.

PMID- 17234916
TI  - A molecule carrier.
AB  - We found that anthraquinone diffuses along a straight line across a flat, highly
      symmetric Cu111 surface. It can also reversibly attach one or two CO2 molecules
      as "cargo" and act as a "molecule carrier," thereby transforming the diffusive
      behavior of the CO2 molecules from isotropic to linear. Density functional theory
      calculations indicated a substrate-mediated attraction of approximately 0.12
      electron volt (eV). Scanning tunneling microscopy revealed individual steps of
      the molecular complex on its diffusion pathway, with increases of approximately
      0.03 and approximately 0.02 eV in the diffusion barrier upon attachment of the
      first and second CO2 molecule, respectively.

PMID- 17234918
TI  - Neurobiology. A surprising connection between memory and imagination.

PMID- 17234919
TI  - Scientific publishing. Fossil dealers launch research journal.

PMID- 17234921
TI  - Stem cell debate. Scientists protest 'misrepresentation' as Senate vote looms.

PMID- 17234920
TI  - Molecular biology. Trafficking protein suspected in Alzheimer's disease.

PMID- 17234922
TI  - Regulatory science. Panel pans proposed change in U.S. risk assessment.

PMID- 17234923
TI  - Scientific misconduct. Former Hwang colleague faked monkey data, U.S. says.

PMID- 17234924
TI  - Astrobiology. Astrobiology fights for its life.

PMID- 17234925
TI  - Astrobiology. It rains in Spain and wilts in Australia.

PMID- 17234926
TI  - Astrobiology. Pete Worden 'Ames' for the Moon and beyond.

PMID- 17234927
TI  - Astrobiology. Robot seeks new life--and new funding--in the abyss of Zacaton.

PMID- 17234929
TI  - William K. Hartmann profile. Renaissance man of the solar system.

PMID- 17234928
TI  - Biomechanics. Crab's downfall reveals a hole in biomechanics studies.

PMID- 17234931
TI  - Moving toward decarbonization.

PMID- 17234930
TI  - Treating diseases with adult stem cells.

PMID- 17234932
TI  - Comment on "The geometry of musical chords".
AB  - Tymoczko (Reports, 7 July 2006, p. 72) proposed that the familiar sonorities of
      Western tonal music cluster around the center of a multidimensional orbifold.
      However, this is not true for all tonal progressions. When prototypical three
      voice cadential progressions by Bach converge on the tonic, the chords migrate
      from the center to the edge of the orbifold.

PMID- 17234933
TI  - Science for development. Poverty reduction through animal health.

PMID- 17234934
TI  - Neuroscience. Is more neurogenesis always better?

PMID- 17234935
TI  - Geochemistry. Fuel for plate tectonics.

PMID- 17234936
TI  - Neuroscience. A push-me pull-you neural design.

PMID- 17234938
TI  - Materials science. Ordering up the minimum thermal conductivity of solids.

PMID- 17234937
TI  - Ecology. Managing farming's footprint on biodiversity.

PMID- 17234939
TI  - Enabling Europe to innovate.
AB  - As activities that relate to innovation become increasingly global and open and
      so draw the private and public sectors into complex networks of partnerships,
      these activities also tend to concentrate where the ecosystem is most supportive.
      European public policy, which in recent years has emphasized the importance of
      research and development (R&D) in achieving competitive knowledge-based
      societies, is shifting toward approaches that address the broader qualities
      required of favorable ecosystems for innovation in a global economy, thereby
      incorporating the roles of market demand, public procurement, and regulation, as
      well as science, education, and industrial R&D, as part of determining effective
      innovation policies.

PMID- 17234941
TI  - Electric field-induced modification of magnetism in thin-film ferromagnets.
AB  - A large electric field at the surface of a ferromagnetic metal is expected to
      appreciably change its electron density. In particular, the metal's intrinsic
      magnetic properties, which are commonly regarded as fixed material constants,
      will be affected. This requires, however, that the surface has a strong influence
      on the material's properties, as is the case with ultrathin films. We
      demonstrated that the magnetocrystalline anisotropy of ordered iron-platinum
      (FePt) and iron-palladium (FePd) intermetallic compounds can be reversibly
      modified by an applied electric field when immersed in an electrolyte. A voltage
      change of -0.6 volts on 2-nanometer-thick films altered the coercivity by -4.5
      and +1% in FePt and FePd, respectively. The modification of the magnetic
      parameters was attributed to a change in the number of unpaired d electrons in
      response to the applied electric field. Our device structure is general and
      should be applicable for characterization of other thin-film magnetic systems.

PMID- 17234940
TI  - Brilliant whiteness in ultrathin beetle scales.
AB  - The colored appearances of animals are controlled by pigmentation, highly
      periodic ultrastructure, or a combination of both. Whiteness, however, is less
      common and is generated by neither of these, because it requires scattering
      processes appropriate for all visible wavelengths. We report whiteness resulting
      from a three-dimensional photonic solid in the scales of Cyphochilus spp.
      beetles. Their scales are characterized by their exceptional whiteness, their
      perceived brightness, and their optical brilliance, but they are only 5
      micrometers thick. This thickness is at least two orders of magnitude thinner
      than common synthetic systems designed for equivalent-quality whiteness.

PMID- 17234942
TI  - Unexpected stability of Al4H6: a borane analog?
AB  - Whereas boron has many hydrides, aluminum has been thought to exhibit relatively
      few. A combined anion photoelectron and density functional theory computational
      study of the Al4H-6 anion and its corresponding neutral, Al4H6, showed that Al4H6
      can be understood in terms of the Wade-Mingos rules for electron counting,
      suggesting that it may be a borane analog. The data support an Al4H6 structure
      with a distorted tetrahedral aluminum atom framework, four terminal Al-H bonds,
      and two sets of counter-positioned Al-H-Al bridging bonds. The large gap between
      the highest occupied and the lowest unoccupied molecular orbitals found for
      Al4H6, together with its exceptionally high heat of combustion, further suggests
      that Al4H6 may be an important energetic material if it can be prepared in bulk.

PMID- 17234943
TI  - Divalent metal nanoparticles.
AB  - Nanoparticles can be used as the building blocks for materials such as
      supracrystals or ionic liquids. However, they lack the ability to bond along
      specific directions as atoms and molecules do. We report a simple method to place
      target molecules specifically at two diametrically opposed positions in the
      molecular coating of metal nanoparticles. The approach is based on the
      functionalization of the polar singularities that must form when a curved surface
      is coated with ordered monolayers, such as a phase-separated mixture of ligands.
      The molecules placed at these polar defects have been used as chemical handles to
      form nanoparticle chains that in turn can generate self-standing films.

PMID- 17234944
TI  - Global-scale similarities in nitrogen release patterns during long-term
      decomposition.
AB  - Litter decomposition provides the primary source of mineral nitrogen (N) for
      biological activity in most terrestrial ecosystems. A 10-year decomposition
      experiment in 21 sites from seven biomes found that net N release from leaf
      litter is dominantly driven by the initial tissue N concentration and mass
      remaining regardless of climate, edaphic conditions, or biota. Arid grasslands
      exposed to high ultraviolet radiation were an exception, where net N release was
      insensitive to initial N. Roots released N linearly with decomposition and
      exhibited little net N immobilization. We suggest that fundamental constraints on
      decomposer physiologies lead to predictable global-scale patterns in net N
      release during decomposition.

PMID- 17234945
TI  - Water solubility in aluminous orthopyroxene and the origin of Earth's
      asthenosphere.
AB  - Plate tectonics is based on the concept of rigid lithosphere plates sliding on a
      mechanically weak asthenosphere. Many models assume that the weakness of the
      asthenosphere is related to the presence of small amounts of hydrous melts.
      However, the mechanism that may cause melting in the asthenosphere is not well
      understood. We show that the asthenosphere coincides with a zone where the water
      solubility in mantle minerals has a pronounced minimum. The minimum is due to a
      sharp decrease of water solubility in aluminous orthopyroxene with depth, whereas
      the water solubility in olivine continuously increases with pressure. Melting in
      the asthenosphere may therefore be related not to volatile enrichment but to a
      minimum in water solubility, which causes excess water to form a hydrous silicate
      melt.

PMID- 17234946
TI  - Nonequilibrium mechanics of active cytoskeletal networks.
AB  - Cells both actively generate and sensitively react to forces through their
      mechanical framework, the cytoskeleton, which is a nonequilibrium composite
      material including polymers and motor proteins. We measured the dynamics and
      mechanical properties of a simple three-component model system consisting of
      myosin II, actin filaments, and cross-linkers. In this system, stresses arising
      from motor activity controlled the cytoskeletal network mechanics, increasing
      stiffness by a factor of nearly 100 and qualitatively changing the viscoelastic
      response of the network in an adenosine triphosphate-dependent manner. We present
      a quantitative theoretical model connecting the large-scale properties of this
      active gel to molecular force generation.

PMID- 17234947
TI  - Farmland biodiversity and the footprint of agriculture.
AB  - Sustainable development requires the reconciliation of demands for biodiversity
      conservation and increased agricultural production. Assessing the impact of novel
      farming practices on biodiversity and ecosystem services is fundamental to this
      process. Using farmland birds as a model system, we present a generic risk
      assessment framework that accurately predicts each species' current conservation
      status and population growth rate associated with past changes in agriculture. We
      demonstrate its value by assessing the potential impact on biodiversity of two
      controversial land uses, genetically modified herbicide-tolerant crops and agri
      environment schemes. This framework can be used to guide policy and land
      management decisions and to assess progress toward sustainability targets.

PMID- 17234948
TI  - Control of Drosophila gastrulation by apical localization of adherens junctions
      and RhoGEF2.
AB  - A hallmark of epithelial invagination is the constriction of cells on their
      apical sides. During Drosophila gastrulation, apical constrictions under the
      control of the transcription factor Twist lead to the invagination of the
      mesoderm. Twist-controlled G protein signaling is involved in mediating the
      invagination but is not sufficient to account for the full activity of Twist. We
      identified a Twist target, the transmembrane protein T48, which acts in
      conjunction with G protein signaling to orchestrate shape changes. Together with
      G protein signaling, T48 recruits adherens junctions and the cytoskeletal
      regulator RhoGEF2 to the sites of apical constriction, ensuring rapid and intense
      changes in cell shape.

PMID- 17234949
TI  - High-throughput identification of catalytic redox-active cysteine residues.
AB  - Cysteine (Cys) residues often play critical roles in proteins; however,
      identification of their specific functions has been limited to case-by-case
      experimental approaches. We developed a procedure for high-throughput
      identification of catalytic redox-active Cys in proteins by searching for
      sporadic selenocysteine-Cys pairs in sequence databases. This method is
      independent of protein family, structure, and taxon. We used it to selectively
      detect the majority of known proteins with redox-active Cys and to make
      additional predictions, one of which was verified. Rapid accumulation of sequence
      information from genomic and metagenomic projects should allow detection of many
      additional oxidoreductase families as well as identification of redox-active Cys
      in these proteins.

PMID- 17234950
TI  - Balanced inhibition and excitation drive spike activity in spinal half-centers.
AB  - Many limb movements are composed of alternating flexions and extensions. However,
      the underlying spinal network mechanisms remain poorly defined. Here, we show
      that the intensity of synaptic excitation and inhibition in limb motoneurons
      varies in phase rather than out of phase during rhythmic scratchlike network
      activity in the turtle. Inhibition and excitation peak with the total neuron
      conductance during the depolarizing waves of scratch episodes. Furthermore, spike
      activity is driven by depolarizing synaptic transients rather than pacemaker
      properties. These findings show that balanced excitation and inhibition and
      irregular firing are fundamental motifs in certain spinal network functions.

PMID- 17234951
TI  - Wandering minds: the default network and stimulus-independent thought.
AB  - Despite evidence pointing to a ubiquitous tendency of human minds to wander,
      little is known about the neural operations that support this core component of
      human cognition. Using both thought sampling and brain imaging, the current
      investigation demonstrated that mind-wandering is associated with activity in a
      default network of cortical regions that are active when the brain is "at rest."
      In addition, individuals' reports of the tendency of their minds to wander were
      correlated with activity in this network.

PMID- 17234952
TI  - Smooth muscle and neural mechanisms contributing to the downregulation of
      neonatal rat spontaneous bladder contractions during postnatal development.
AB  - Spontaneous bladder contractions (SBCs) in the neonatal rat urinary bladder
      change from a high-amplitude, low-frequency pattern to a low-amplitude, high
      frequency pattern during the first 6 wk of life. Understanding the mechanism of
      this developmental change may provide insights into the causes of bladder
      overactivity in adults. In vitro whole bladder preparations from Sprague-Dawley
      rats were used to study the modulation of SBCs by calcium-activated potassium
      channels (K(Ca)) and electrical field stimulation from 3 days to 6 wk of life.
      SBCs in 3-day-old bladders were unmasked by treatment with iberiotoxin (100 nM),
      an inhibitor of large conductance K(Ca) (BK) channels, or apamin (100 nM), an
      inhibitor of small conductance K(Ca) (SK) channels. Iberiotoxin significantly
      increased the magnitude of SBCs at 2-3 wk, whereas apamin was only effective at 6
      wk. In 1-2 wk bladders, exposure to room temperature Krebs solution decreased
      SBCs. This decrease was reversed by activating intramural nerves with electrical
      field stimulation. The effect of electrical field stimulation was inhibited by
      atropine (1 microM), suramin (10 microM), or pretreatment with tetrodotoxin (1
      microM) but was not reversed by tetrodotoxin applied after electrical field
      stimulation. BK-alpha mRNA increased threefold, and BK-alpha protein increased
      fivefold from 3 days to 6 wk. These data suggest that BK channels play an
      important role in the regulation of SBCs in the neonatal bladder and that both
      increased BK channel activity, as well as changes in smooth muscle sensitivity to
      locally released neurotransmitters contribute to the downregulation of SBCs
      during early postnatal development.

PMID- 17234953
TI  - Comparative changes in the blood-brain barrier and cerebral infarction of SHR and
      WKY rats.
AB  - Hypertension is involved in the exacerbation of stroke. It is unclear how blood
      brain barrier (BBB) tight-junction (TJ) and ion transporter proteins critical for
      maintaining brain homeostasis contribute to cerebral infarction during
      hypertension development. In the present study, we investigated cerebral infarct
      volume following permanent 4-h middle cerebral artery occlusion (MCAO) and
      characterized the expression of BBB TJ and ion transporter proteins in brain
      microvessels of spontaneously hypertensive rats (SHR) compared with age-matched
      Wistar-Kyoto (WKY) rats at 5 wk (prehypertension), 10 wk (early-stage
      hypertension), and 15 wk (later-stage hypertension) of age. Hypertensive SHR show
      increased infarct volume following MCAO compared with WKY control rats. BBB TJ
      and ion transporter proteins, known to contribute to edema and fluid volume
      changes in the brain, show differential protein expression patterns during
      hypertension development. Western blot analysis of TJ protein zonula occludens-2
      (ZO-2) showed decreased expression, while ion transporter, Na(+)/H(+) exchanger 1
      (NHE-1), was markedly increased in hypertensive SHR. Expression of TJ proteins ZO
      1, occludin, actin, claudin-5, and Na(+)-K(+)-2Cl(-) cotransporter remain
      unaffected in SHR compared with control. Selective inhibition of NHE-1 using
      dimethylamiloride significantly attenuated ischemia-induced infarct volume in
      hypertensive SHR following MCAO, suggesting a novel role for NHE-1 in the brain
      in the regulation of ischemia-induced infarct volume in SHR.

PMID- 17234954
TI  - Glutamine's protection against sepsis and lung injury is dependent on heat shock
      protein 70 expression.
AB  - Glutamine (GLN) has been shown to protect against inflammatory injury and illness
      in experimental and clinical settings. The mechanism of this protection is
      unknown; however, laboratory and clinical trial data have indicated a
      relationship between GLN-mediated protection and enhanced heat shock protein 70
      (HSP70) expression. The aim of this study was to examine the hypothesis that
      GLN's beneficial effect on survival, tissue injury, and inflammatory response
      after inflammatory injury is dependent on HSP70 expression. Mice with a specific
      deletion of the HSP70 gene underwent cecal ligation and puncture (CLP)-induced
      sepsis and were treated with GLN (0.75 g/kg) or a saline placebo 1 h post-CLP.
      Lung tissue NF-kappaB activation, inflammatory cytokine response, and lung injury
      were assessed post-CLP. Survival was assessed for 5 days post-CLP. Our results
      indicate that GLN administration improved survival in Hsp70(+/+) mice vs.
      Hsp70(+/+) mice not receiving GLN; however, GLN exerted no survival benefit in
      Hsp70(-/-) mice. This was accompanied by a significant decrease in lung injury,
      attenuation of NF-kappaB activation, and proinflammatory cytokine expression in
      GLN-treated Hsp70(+/+) mice vs. Hsp70(+/+) mice not receiving GLN. In the Hsp70(
      /-) mice, GLN's attenuation of lung injury, NF-kappaB activation, and
      proinflammatory cytokine expression was lost. These results confirm our
      hypothesis that HSP70 expression is required for GLN's effects on survival,
      tissue injury, and the inflammatory response after global inflammatory injury.

PMID- 17234955
TI  - The importance of limitations in aerobic metabolism, glycolysis, and membrane
      excitability for the development of high-frequency fatigue in isolated rat soleus
      muscle.
AB  - We investigated the role of limitations in aerobic metabolism, glycolysis, and
      membrane excitability for development of high-frequency fatigue in isolated rat
      soleus muscle. Muscles mounted on force transducers were incubated in buffer
      bubbled with 5% CO(2) and either 95% O(2) (oxygenated) or 95% N(2) (anoxic) and
      stimulated at 60 Hz continuously for 30-120 s or intermittently for 120 s.
      Cyanide (2 mM) and 2-deoxyglucose (10 mM) were used to inhibit aerobic metabolism
      and both glycolysis and aerobic metabolism, respectively. Excitability was
      reduced by carbacholine (10 microM), a nicotinic ACh receptor agonist, or ouabain
      (10 microM), an Na(+)-K(+) pump inhibitor. Membrane excitability was measured by
      recording M waves. Intracellular Na(+) and K(+) contents and membrane potentials
      were measured by flame photometry and microelectrodes, respectively. During 120 s
      of continuous stimulation, oxygenated and anoxic muscles showed the same force
      loss. In oxygenated muscles, cyanide did not alter force loss for up to 90 s,
      whereas 2-deoxyglucose increased force loss (by 19-69%; P < 0.01) from 14 s of
      stimulation. In oxygenated muscles, 60 s of stimulation reduced force, M wave
      area, and amplitude by 70-90% (P < 0.001). Carbacholine or ouabain increased
      intracellular Na(+) content (P < 0.001), induced a 7- to 8-mV membrane
      depolarization (P < 0.001), and accelerated the rate of force loss (by 250-414%)
      during 30 s of stimulation (P < 0.001). Similar effects were seen with
      intermittent stimulation. In conclusion, limitations in glycolysis and
      subsequently also in aerobic metabolism, as well as membrane excitability but not
      aerobic metabolism alone, appear to play an important role in the development of
      high-frequency fatigue in isolated rat soleus muscle.

PMID- 17234956
TI  - Prevention of diet-induced obesity and impaired glucose tolerance in rats
      following administration of leptin to their mothers.
AB  - Absence of leptin is known to disrupt the development of energy balance
      regulatory mechanisms. We investigated whether administration of leptin to
      normally nourished rats affects energy balance in their offspring. Leptin (2
      mg.kg(-1).day(-1)) was administered from day 14 of pregnancy and throughout
      lactation. Male and female offspring were fed either on chow or on high-fat diets
      that elicited similar levels of obesity in the sexes from 6 wk to 15 mo of age.
      Treatment of the dams with leptin prevented diet-induced increases in the rate of
      weight gain, retroperitoneal fat pad weight, area under the intraperitoneal
      glucose tolerance curve, and fasting plasma insulin concentration in female
      offspring. In the male offspring, the diet-induced increase in weight gain was
      prevented and increased fat pad weight was reduced. Energy intake per rat was
      higher in response to the obesogenic diet in male offspring of saline-treated but
      not leptin-treated dams. A similar trend was seen in 3-mo-old female offspring.
      Energy expenditure at 3 mo of age was higher for a given body weight in female
      offspring of leptin-treated compared with saline-treated dams when these animals
      were fed on the obesogenic diet. A similar trend was seen for male rats fed on
      the obesogenic diet. Thus leptin levels during pregnancy and lactation can affect
      the development of energy balance regulatory systems in their offspring.

PMID- 17234957
TI  - Surviving sepsis: bcl-2 overexpression modulates splenocyte transcriptional
      responses in vivo.
AB  - We hypothesized that spleen microarray gene expression profiles analyzed with
      contemporary pathway analysis software would provide molecular pathways of
      interest and target genes that might help explain the effect of bcl-2 on
      improving survival during sepsis. Two mouse models of sepsis, cecal ligation and
      puncture and tracheal instillation of Pseudomonas aeruginosa, were tested in both
      wild-type mice and mice that overexpress bcl-2. Whole spleens were obtained 6 h
      after septic injury. DNA microarray transcriptional profiles were obtained using
      the Affymetrix 430A GeneChip, containing 22,690 elements. Ingenuity Pathway
      Analysis software was used to construct hypothetical transcriptional networks
      that changed in response to sepsis and expression of the bcl-2 transgene. A
      conservative approach was used wherein only changes induced by both abdominal and
      pulmonary sepsis were studied. At 6 h, sepsis induced alterations in the
      abundance of hundreds of spleen genes, including a number of proinflammatory
      mediators (e.g., interleukin-6). These sepsis-induced alterations were blocked by
      expression of the bcl-2 transgene. Network analysis implicated a number of bcl-2
      related apoptosis genes, including bcl2L11 (bim), bcl-2L2 (bcl-w), bmf, and mcl
      1. Sepsis in bcl-2 transgenic animals resulted in alteration of RNA abundance for
      only a single gene, ceacam1. These findings are consistent with sepsis-induced
      alterations in the balance of pro- and anti-apoptotic transcriptional networks.
      In addition, our data suggest that the ability of bcl-2 overexpression to improve
      survival in sepsis in this model is related in part to prevention of sepsis
      induced alterations in spleen transcriptional responses.

PMID- 17234958
TI  - Effect of extracellular osmolality on cell volume and resting metabolism in
      mammalian skeletal muscle.
AB  - The purpose of the present investigation was to establish an in vitro mammalian
      skeletal muscle model to study acute alterations in resting skeletal muscle cell
      volume. Isolated, whole muscles [soleus and extensor digitorum longus (EDL)] were
      dissected from Long-Evans rats and incubated for 60 min in Sigma medium 199 (1 g
      of resting tension, bubbled with 95% O(2)-5% O(2), 30 +/- 2 degrees C, and pH
      7.4). Medium osmolality was altered to simulate hyposmotic (190 +/- 10 mmol/kg)
      or hyperosmotic conditions (400 +/- 10 mmol/kg), whereas an isosmotic condition
      (290 +/- 10 mmol/kg) served as a control. After incubation, relative water
      content of the muscle decreased with hyperosmotic and increased with hyposmotic
      condition in both muscle types (P < 0.05). The cross-sectional area of soleus
      type I and type II fibers increased (P < 0.05) in hyposmotic, whereas
      hyperosmotic exposure led to no detectable changes. The EDL type II fiber area
      decreased in the hyperosmotic condition and increased after hyposmotic exposure,
      whereas no change was observed in EDL type I fibers. Furthermore, exposure to the
      hyperosmotic condition in both muscle types resulted in decreased muscle ATP and
      phosphocreatine (P < 0.05) contents and increased creatine and lactate contents
      (P < 0.05) compared with control and hyposmotic conditions. This isolated
      skeletal muscle model proved viable and demonstrated that altering extracellular
      osmolality could cause acute alterations in muscle water content and resting
      muscle metabolism.

PMID- 17234959
TI  - A psychophysical and electrophysiological analysis of salt taste in Trpv1 null
      mice.
AB  - Current evidence suggests salt taste transduction involves at least two
      mechanisms, one that is amiloride sensitive and appears to use apically located
      epithelial sodium channels relatively selective for Na(+) and a second that is
      amiloride insensitive and uses a variant of the transient receptor potential
      vanilloid receptor 1 (TRPV1) that serves as a nonspecific cation channel. To
      provide a functional context for these findings, we trained Trpv1 knockout (KO)
      and wild-type (WT) C57BL/6J mice (n = 9 or 10/group) in a two-response operant
      discrimination procedure and measured detection thresholds to NaCl and KCl with
      and without amiloride. The KO and WT mice had similar detection thresholds for
      NaCl and KCl. Amiloride shifted the NaCl sensitivity curve to the same degree in
      both groups and had virtually no effect on KCl thresholds. In addition, a more
      detailed analysis of chorda tympani nerve (CT) responses to NaCl, with and
      without benzamil (Bz, an amiloride analog) treatment revealed that the tonic
      portion of the CT response of KO mice to NaCl + Bz was absent, but both KO and WT
      mice displayed some degree of a phasic response to NaCl with and without Bz.
      Because these transients constitute the entire CT response to NaCl + Bz in Trpv1
      KO mice, it is possible that these signals are sufficient to maintain normal NaCl
      detectabilty in the behavioral task used here. Additionally, there may be other
      amiloride-insensitive salt transduction mechanisms in taste receptor fields other
      than the anterior tongue that maintain normal salt detection performance in the
      KO mice.

PMID- 17234960
TI  - Metabolic rate does not scale with body mass in cultured mammalian cells.
AB  - The allometric scaling of metabolic rate with organism body mass can be partially
      accounted for by differences in cellular metabolic rates. For example,
      hepatocytes isolated from horses consume almost 10-fold less oxygen per unit time
      as mouse hepatocytes [Porter and Brand, Am J Physiol Regul Integr Comp Physiol
      269: R226-R228, 1995]. This could reflect a genetically programmed, species
      specific, intrinsic metabolic rate set point, or simply the adaptation of
      individual cells to their particular in situ environment (i.e., within the
      organism). We studied cultured cell lines derived from 10 mammalian species with
      donor body masses ranging from 5 to 600,000 g to determine whether cells
      propagated in an identical environment (media) exhibited metabolic rate scaling.
      Neither metabolic rate nor the maximal activities of key enzymes of oxidative or
      anaerobic metabolism scaled significantly with donor body mass in cultured cells,
      indicating the absence of intrinsic, species-specific, cellular metabolic rate
      set points. Furthermore, we suggest that changes in the metabolic rates of
      isolated cells probably occur within 24 h and involve a reduction of cellular
      metabolism toward values observed in lower metabolic rate organisms. The rate of
      oxygen delivery has been proposed to limit cellular metabolic rates in larger
      organisms. To examine the effect of oxygen on steady-state cellular respiration
      rates, we grew cells under a variety of physiologically relevant oxygen regimens.
      Long-term exposure to higher medium oxygen levels increased respiration rates of
      all cells, consistent with the hypothesis that higher rates of oxygen delivery in
      smaller mammals might increase cellular metabolic rates.

PMID- 17234961
TI  - Nitric oxide-dependent and -independent mechanisms are involved in TNF-alpha 
      induced depression of cardiac myocyte contractility.
AB  - Previous studies have demonstrated the presence of myocardial depression in
      clinical and experimental septic shock. This response is mediated, in part,
      through circulating TNF-alpha-induced, nitric oxide-dependent, depression of
      basal myocyte contractility. Other mechanisms of early myocardial dysfunction
      involving decreased response to adrenergic stimulation may exist. This study
      evaluated the presence and nitric oxide dependence of impaired adrenergic
      response to TNF-alpha in in vitro cardiac myocytes. The contraction of
      electrically paced neonatal rat cardiac myocytes in tissue culture was quantified
      using a closed-loop video tracking system. TNF-alpha induced depression of
      baseline contractility over the first 20 min of cardiac myocyte exposure. This
      effect was blocked by N-methyl-arginine (NMA), a nitric oxide synthase inhibitor,
      in all studies. Contractile and cAMP response to increasing concentrations of
      isoproterenol was deficient in cardiac myocytes exposed to TNF-alpha regardless
      of the presence of NMA. In contrast, increasing concentrations of forskolin (a
      direct stimulant of adenylate cyclase) and dibutyryl cAMP (a metabolically active
      membrane-soluble analog of cAMP) completely reversed TNF-alpha-mediated
      depression, though only in the presence of NMA. Forskolin-stimulated cAMP
      generation remained intact regardless of NMA. Increasing concentrations of
      exogenous calcium chloride, unlike other inotropic agents, corrected TNF-alpha
      mediated defects of contractility independent of the presence of NMA. These data
      suggest that TNF-alpha exposure is associated with a second nitric oxide
      independent but calcium-dependent early depressant mechanism that is manifested
      by reduced contractile and cAMP response to beta-adrenergic stimulation.

PMID- 17234962
TI  - Mechanisms of abnormal calcium homeostasis in mutations responsible for
      catecholaminergic polymorphic ventricular tachycardia.
AB  - Catecholaminergic polymorphic ventricular tachycardia is a heritable arrhythmia
      unmasked by exertion or stress and is characterized by triggered activity and
      sudden cardiac death. In this study, we simulated mutations in 2 genes linked to
      catecholaminergic polymorphic ventricular tachycardia, the first located in
      calsequestrin (CSQN2) and the second in the ryanodine receptor (RyR2). The aim of
      the study was to investigate the mechanistic basis for spontaneous Ca2+ release
      events that lead to delayed afterdepolarizations in affected patients.
      Sarcoplasmic reticulum (SR) luminal Ca2+ sensing was incorporated into a model of
      the human ventricular myocyte, and CSQN2 mutations were modeled by simulating
      disrupted RyR2 luminal Ca2+ sensing. In voltage-clamp mode, the mutant CSQN2
      model recapitulated the smaller calcium transients, smaller time to peak calcium
      transient, and accelerated recovery from inactivation seen in experiments. In
      current clamp mode, in the presence of beta stimulation, we observed delayed
      afterdepolarizations, suggesting that accelerated recovery of RyR2 induced by
      impaired luminal Ca2+ sensing underlies the triggered activity observed in mutant
      CSQN2-expressing myocytes. In current-clamp mode, in a model of mutant RyR2 that
      is characterized by reduced FKBP12.6 binding to the RyR2 on beta stimulation, the
      impaired coupled gating characteristic of these mutations was modeled by reducing
      cooperativity of RyR2 activation. In current-clamp mode, the mutant RyR2 model
      exhibited increased diastolic RyR2 open probability that resulted in formation of
      delayed afterdepolarizations. In conclusion, these minimal order models of mutant
      CSQN2 and RyR2 provide plausible mechanisms by which defects in RyR2 gating may
      lead to the cellular triggers for arrhythmia, with implications for the
      development of targeted therapy.

PMID- 17234963
TI  - Pharmacologically preconditioned skeletal myoblasts are resistant to oxidative
      stress and promote angiomyogenesis via release of paracrine factors in the
      infarcted heart.
AB  - Strategies to enhance skeletal myoblast (SkM) survival after transplantation in
      the ischemic heart have achieved little success. We posit that preconditioned
      (PC) SkMs show improved survival and promote repair of the infarcted myocardium
      via paracrine signaling after transplantation. SkMs from male Fischer-344 rats
      (rSkMs) were PC for 30 minutes with 200 micromol/L diazoxide. Treatment of PC
      rSkMs with 100 micromol/L H(2)O(2) for 2 hours resulted in significantly reduced
      cell injury, as shown by lactate dehydrogenase-release assay, and prevented
      apoptosis, as demonstrated by cytochrome c translocation, TUNEL, annexin V
      staining, and preservation of mitochondrial membrane potential. PC rSkMs
      expressed elevated phospho-Akt (1.85-fold), basic fibroblast growth factor (1.44
      fold), hepatocyte growth factor (2.26-fold), and cyclooxygenase-2 (1.33-fold) as
      compared with non-PC rSkMs. For in vivo studies, female Fischer-344 rats after
      permanent coronary artery ligation were grouped (n=12/group) to receive 80 microL
      of basal medium without rSkMs (group 1) or containing 1.5 x 10(6) non-PC (group
      2) or PC (group 3) rSkMs. Real-time PCR for sry gene 4 days after transplantation
      (n=4/group) showed 1.93-fold higher survival of rSkMs in group 3 as compared with
      group 2. Four weeks later, echocardiography revealed improved indices of left
      ventricular function, including ejection fraction and fractional shortening in
      group 3 (P<0.02) as compared with groups 1 and 2. Blood vessel count per surface
      area (at x400 magnification) was highest in scar and periscar areas in group 3 as
      compared with the other groups (P<0.05). We conclude that activation of signaling
      pathways of preconditioning in SkMs promoted their survival by release of
      paracrine factors to promote angiomyogenesis in the infarcted heart.
      Transplantation of PC SkMs for heart cell therapy is an innovative approach in
      the clinical perspective.

PMID- 17234964
TI  - Contrasting gene expression profiles in two canine models of atrial fibrillation.
AB  - Gene-expression changes in atrial fibrillation patients reflect both underlying
      heart-disease substrates and changes because of atrial fibrillation-induced
      atrial-tachycardia remodeling. These are difficult to separate in clinical
      investigations. This study assessed time-dependent mRNA expression-changes in
      canine models of atrial-tachycardia remodeling and congestive heart failure. Five
      experimental groups (5 dogs/group) were submitted to atrial (ATP, 400 bpm x 24
      hours, 1 or 6 weeks) or ventricular (VTP, 240 bpm x 24 hours or 2 weeks)
      tachypacing. The expression of approximately 21,700 transcripts was analyzed by
      microarray in isolated left-atrial cardiomyocytes and (for 18 genes) by real-time
      RT-PCR. Protein-expression changes were assessed by Western blot. In VTP, a large
      number of significant mRNA-expression changes occurred after both 24 hours (2209)
      and 2 weeks (2720). In ATP, fewer changes occurred at 24 hours (242) and fewer
      still (87) at 1 week, with no statistically-significant alterations at 6 weeks.
      Expression changes in VTP varied over time in complex ways. Extracellular matrix
      related transcripts were strongly upregulated by VTP consistent with its
      pathophysiology, with 8 collagen-genes upregulated >10-fold, fibrillin-1 8-fold
      and MMP2 4.5-fold at 2 weeks (time of fibrosis) but unchanged at 24 hours. Other
      extracellular matrix genes (eg, fibronectin, lysine oxidase-like 2) increased at
      both time-points ( approximately 10, approximately 5-fold respectively). In ATP,
      mRNA-changes almost exclusively represented downregulation and were
      quantitatively smaller. This study shows that VTP-induced congestive heart
      failure and ATP produce qualitatively different temporally-evolving patterns of
      gene-expression change, and that specific transcriptomal responses associated
      with atrial fibrillation versus underlying heart disease substrates must be
      considered in assessing gene-expression changes in man.

PMID- 17234965
TI  - Notch ligand Delta-like 1 is essential for postnatal arteriogenesis.
AB  - Growth of functional arteries is essential for the restoration of blood flow to
      ischemic organs. Notch signaling regulates arterial differentiation upstream of
      ephrin-B2 during embryonic development, but its role during postnatal
      arteriogenesis is unknown. Here, we identify the Notch ligand Delta-like 1 (Dll1)
      as an essential regulator of postnatal arteriogenesis. Dll1 expression was
      specifically detected in arterial endothelial cells, but not in venous
      endothelial cells or capillaries. During ischemia-induced arteriogenesis
      endothelial Dll1 expression was strongly induced, Notch signaling activated and
      ephrin-B2 upregulated, whereas perivascular cells expressed proangiogenic
      vascular endothelial growth factor, and the ephrin-B2 activator EphB4. In
      heterozygous Dll1 mutant mice endothelial Notch activation and ephrin-B2
      induction after hindlimb ischemia were absent, arterial collateral growth was
      abrogated and recovery of blood flow was severely impaired, but perivascular
      vascular endothelial growth factor and EphB4 expression was unaltered. In vitro,
      angiogenic growth factors synergistically activated Notch signaling by induction
      of Dll1, which was necessary and sufficient to regulate ephrin-B2 expression and
      to induce ephrin-B2 and EphB4-dependent branching morphogenesis in human arterial
      EC. Thus, Dll1-mediated Notch activation regulates ephrin-B2 expression and
      postnatal arteriogenesis.

PMID- 17234966
TI  - Beta-adrenergic enhancement of sarcoplasmic reticulum calcium leak in cardiac
      myocytes is mediated by calcium/calmodulin-dependent protein kinase.
AB  - Enhanced cardiac diastolic Ca leak from the sarcoplasmic reticulum (SR) ryanodine
      receptor may reduce SR Ca content and contribute to arrhythmogenesis. We tested
      whether beta-adrenergic receptor (beta-AR) agonists increased SR Ca leak in
      intact rabbit ventricular myocytes and whether this depends on protein kinase A
      or Ca/calmodulin-dependent protein kinase II (CaMKII) activity. SR Ca leak was
      assessed by acute block of the ryanodine receptor by tetracaine and assessment of
      the consequent shift of Ca from cytosol to SR (measured at various SR Ca loads
      induced by varying frequency). Cytosolic [Ca] ([Ca](i)) and SR Ca load
      ([Ca](SRT)) were assessed using fluo-4. beta-AR activation by isoproterenol
      dramatically increased SR Ca leak. However, this effect was not inhibited by
      blocking protein kinase A by H-89, despite the expected reversal of the
      isoproterenol-induced enhancement of Ca transient amplitude and [Ca](i) decline
      rate. In contrast, inhibitors of CaMKII, KN-93, or autocamtide-2-related
      inhibitory peptide II or beta-AR blockade reversed the isoproterenol-induced
      enhancement of SR Ca leak, and CaMKII inhibition could even reduce leak below
      control levels. Forskolin, which bypasses the beta-AR in activating adenylate
      cyclase and protein kinase A, did not increase SR Ca leak, despite robust
      enhancement of Ca transient amplitude and [Ca](i) decline rate. The results
      suggest that beta-AR stimulation enhances diastolic SR Ca leak in a manner that
      is (1) CaMKII dependent, (2) not protein kinase A dependent, and 3) not dependent
      on bulk [Ca](i).

PMID- 17234967
TI  - p38-MAPK induced dephosphorylation of alpha-tropomyosin is associated with
      depression of myocardial sarcomeric tension and ATPase activity.
AB  - Our objective in work presented here was to understand the mechanisms by which
      activated p38alpha MAPK depresses myocardial contractility. To test the
      hypothesis that activation of p38 MAPK directly influences sarcomeric function,
      we used transgenic mouse models with hearts in which p38 MAPK was constitutively
      turned on by an upstream activator (MKK6bE). These hearts demonstrated a
      significant depression in ejection fraction after induction of the transgene. We
      also studied hearts of mice expressing a dominant negative p38alpha MAPK.
      Simultaneous determination of tension and ATPase activity of detergent-skinned
      fiber bundles from left ventricular papillary muscle demonstrated a significant
      inhibition of both maximum tension and ATPase activity in the transgenic-MKK6bE
      hearts. Fibers from hearts expressing dominant negative p38alpha MAPK
      demonstrated no significant change in tension or ATPase activity. There were no
      significant changes in phosphorylation level of troponin-T3 and troponin-T4, or
      myosin light chain 2. However, compared with controls, there was a significant
      depression in levels of phosphorylation of alpha-tropomyosin and troponin I in
      fiber bundles from transgenic-MKK6bE hearts, but not from dominant negative
      p38alpha MAPK hearts. Our experiments also showed that p38alpha MAPK colocalizes
      with alpha-actinin at the Z-disc and complexes with protein phosphatases
      (PP2alpha, PP2beta). These data are the first to indicate that chronic activation
      of p38alpha MAPK directly depresses sarcomeric function in association with
      decreased phosphorylation of alpha-tropomyosin.

PMID- 17234968
TI  - Triglyceride-rich lipoproteins prime aortic endothelium for an enhanced
      inflammatory response to tumor necrosis factor-alpha.
AB  - High levels of triglyceride-rich lipoproteins (TGRLs) in blood are linked to
      development of atherosclerosis, yet the mechanisms by which these particles
      initiate inflammation of endothelium are unknown. TGRL isolated from human plasma
      during the postprandial state was examined for its capacity to bind to cultured
      human aortic endothelial cells (HAECs) and alter the acute inflammatory response
      to tumor necrosis factor-alpha. HAECs were repetitively incubated with dietary
      levels of freshly isolated TGRL for 2 hours per day for 1 to 3 days to mimic
      postprandial lipidemia. TGRL induced membrane upregulation of the low-density
      lipoprotein family receptors LRP and LR11, which was inhibited by the low-density
      lipoprotein receptor-associated protein-1. TGRLs alone did not elicit
      inflammation in HAECs but enhanced the inflammatory response via a 10-fold
      increase in sensitivity to cytokine stimulation. This was reflected by increased
      mitogen-activated protein kinase activation, nuclear translocation of NF-kappaB,
      amplified expression of endothelial selectin and VCAM-1, and a subsequent
      increase in monocyte-specific recruitment under shear flow as quantified in a
      microfabricated vascular mimetic device.

PMID- 17234969
TI  - Ca2+/calmodulin kinase II-dependent phosphorylation of ryanodine receptors
      suppresses Ca2+ sparks and Ca2+ waves in cardiac myocytes.
AB  - The multifunctional Ca(2+)/calmodulin-dependent protein kinase II delta(C)
      (CaMKIIdelta(C)) is found in the macromolecular complex of type 2 ryanodine
      receptor (RyR2) Ca(2+) release channels in the heart. However, the functional
      role of CaMKII-dependent phosphorylation of RyR2 is highly controversial. To
      address this issue, we expressed wild-type, constitutively active, or dominant
      negative CaMKIIdelta(C) via adenoviral gene transfer in cultured adult rat
      ventricular myocytes. CaMKII-mediated phosphorylation of RyR2 was reduced,
      enhanced, or unaltered by dominant-negative, constitutively active, or wild-type
      CaMKIIdelta(C) expression, whereas phosphorylation of phospholamban at Thr17, an
      endogenous indicator of CaMKII activity, was at 73%, 161%, or 115% of the control
      group expressing beta-galactosidase (beta-gal), respectively. In parallel with
      the phospholamban phosphorylation, the decay kinetics of global Ca(2+) transients
      was slowed, accelerated, or unchanged, whereas spontaneous Ca(2+) spark activity
      was hyperactive, depressed, or unchanged in dominant-negative, constitutively
      active, or wild-type CaMKIIdelta(C) groups, respectively. When challenged by high
      extracellular Ca(2+), both wild-type and constitutively active CaMKIIdelta(C)
      protected the cells from store overload-induced Ca(2+) release, manifested by a
      approximately 60% suppression of Ca(2+) waves (at 2 to 20 mmol/L extracellular
      Ca(2+)) in spite of an elevated sarcoplasmic reticulum Ca(2+) content, whereas
      dominant-negative CaMKIIdelta(C) promoted Ca(2+) wave production (at 20 mmol/L
      Ca(2+)) with significantly depleted sarcoplasmic reticulum Ca(2+). Taken
      together, our data support the notion that CaMKIIdelta(C) negatively regulates
      RyR2 activity and spontaneous sarcoplasmic reticulum Ca(2+) release, thereby
      affording a negative feedback that stabilizes local and global Ca(2+)-induced
      Ca(2+) release in the heart.

PMID- 17234970
TI  - Molecular pathway for the localized formation of the sinoatrial node.
AB  - The sinoatrial node, which resides at the junction of the right atrium and the
      superior caval vein, contains specialized myocardial cells that initiate the
      heart beat. Despite this fundamental role in heart function, the embryonic origin
      and mechanisms of localized formation of the sinoatrial node have not been
      defined. Here we show that subsequent to the formation of the Nkx2-5-positive
      heart tube, cells bordering the inflow tract of the heart tube give rise to the
      Nkx2-5-negative myocardial cells of the sinoatrial node and the sinus horns.
      Using genetic models, we show that as the myocardium of the heart tube matures,
      Nkx2-5 suppresses pacemaker channel gene Hcn4 and T-box transcription factor gene
      Tbx3, thereby enforcing a progressive confinement of their expression to the
      forming Nkx2-5-negative sinoatrial node and sinus horns. Thus, Nkx2-5 is
      essential for establishing a gene expression border between the atrium and
      sinoatrial node. Tbx3 was found to suppress chamber differentiation, providing an
      additional mechanism by which the Tbx3-positive sinoatrial node is shielded from
      differentiating into atrial myocardium. Pitx2c-deficient fetuses form sinoatrial
      nodes with indistinguishable molecular signatures at both the right and left
      sinuatrial junction, indicating that Pitx2c functions within the left/right
      pathway to suppress a default program for sinuatrial node formation on the left.
      Our molecular pathway provides a mechanism for how pacemaker activity becomes
      progressively relegated to the most recently added components of the venous pole
      of the heart and, ultimately, to the junction of the right atrium and superior
      caval vein.

PMID- 17234971
TI  - Forkhead transcription factor FOXO3a is a negative regulator of angiogenic
      immediate early gene CYR61, leading to inhibition of vascular smooth muscle cell
      proliferation and neointimal hyperplasia.
AB  - Cysteine-rich angiogenic protein 61 (CYR61, CCN1) is an immediate early gene
      expressed in vascular smooth muscle cells (VSMCs) on growth factor stimulation,
      and its expression has been suggested to be associated with postangioplasty
      restenosis. The forkhead transcription factors are reported to play various roles
      in cellular proliferation, apoptosis, and even adaptation to cellular stress. We
      hypothesized that the forkhead transcription factor FOXO3a may regulate CYR61
      expression in VSMCs and investigated the CYR61-modulating effect of FOXO3a in the
      process of vascular response to vasoactive signals and vascular injury. To
      evaluate the effect of FOXO3a on CYR61 expression, rat VSMCs were infected with
      adenoviral vectors expressing constitutively active FOXO3a (Ad-TM-FOXO3a).
      Constitutively active FOXO3a gene transduction suppressed CYR61 expression.
      Luciferase assay with the deletion constructs of the forkhead factor binding
      motif in CYR61 promoter region, which resulted in a significant decrease in
      luciferase expression compared with the intact construct, and chromatin
      immunoprecipitation analysis confirmed transcriptional regulation of CYR61 by
      FOXO3a. Serum and angiotensin II rapidly induced CYR61 expression, which was
      significantly reduced by Ad-TM-FOXO3a. Reduction of VSMC proliferation and
      migration associated with FOXO3a activation was significantly reversed by
      cotransfection of adenoviral vector expressing CYR61, whereas apoptosis induction
      by FOXO3a was not influenced. In a rat balloon carotid arterial injury model,
      CYR61 was rapidly induced in VSMCs in the early stage of injury and remained
      elevated until 14 days, which was suppressed by Ad-TM-FOXO3a transfection. After
      14 days, there was a significant reduction in neointima by FOXO3a transduction
      compared with the control group (0.06+/-0.02 versus 0.20+/-0.07 mm(2), P<0.01).
      Such reduction of neointimal hyperplasia by Ad-TM-FOXO3a was reversed by CYR61
      replenishment. These data suggest that FOXO3a is a negative transcription factor
      of CYR61 and that suppression of CYR61 is among several mechanisms by which
      FOXO3a inhibits VSMC proliferation and neointimal hyperplasia.

PMID- 17234972
TI  - MicroRNAs play an essential role in the development of cardiac hypertrophy.
AB  - MicroRNAs are naturally existing, small, noncoding RNA molecules that
      downregulate posttranscriptional gene expression. Their expression pattern and
      function in the heart remain unknown. Here we report an array of microRNAs that
      are differentially and temporally regulated during cardiac hypertrophy.
      Significantly, the muscle-specific microRNA-1 (miR-1) was singularly
      downregulated as early as day 1 (0.56+/-0.036), persisting through day 7 (0.29+/
      0.14), after aortic constriction-induced hypertrophy in a mouse model.
      Overexpression experiments showed that miR-1 inhibited its in silico-predicted,
      growth-related targets, including Ras GTPase-activating protein (RasGAP), cyclin
      dependent kinase 9 (Cdk9), fibronectin, and Ras homolog enriched in brain (Rheb),
      in addition to protein synthesis and cell size. Thus, we propose that microRNAs
      play an essential regulatory role in the development of cardiac hypertrophy,
      wherein downregulation of miR-1 is necessary for the relief of growth-related
      target genes from its repressive influence and induction of hypertrophy.

PMID- 17234980
TI  - Impact of stroke subtype on blood pressure course during the acute stage of
      cerebral ischemia.

PMID- 17234974
TI  - Reduced force generating capacity in myocytes from chronically ischemic,
      hibernating myocardium.
AB  - The contractile dysfunction of the hibernating myocardium in situ results from
      local environmental factors, but also from intrinsic cellular remodelling that
      may determine reversibility. Previous studies have suggested defects in
      myofilament Ca2+ responsiveness. We prepared single myocytes from control (CTRL,
      n(pigs)=7) and from hibernating myocardium (HIB, n(pigs)=8), removed the
      membranes and measured isometric force development during direct activation of
      the myofilaments. One- and 2-dimensional polyacrylamide gel electrophoresis and
      specific phosphoprotein immunoblotting were performed on tissue homogenates from
      matched samples. Cellular ultrastructure was evaluated using electron microscopy.
      Normalized for cross-sectional area, passive force was not different but maximal
      isometric force was significantly reduced in myocytes from HIB (11.6+/-1.5 kN/m2
      versus 18.7+/-1.6 kN/m2 in CTRL, P<0.05). Ca2+ sensitivity and steepness of the
      normalized force-pCa relationship were not different, and neither was the rate of
      force redevelopment (K(tr)). No alterations were observed in isoform expression,
      phosphorylation or degradation of specific myofibrillar proteins. However, in HIB
      samples the total protein volume density was decreased by 23% (P<0.05). Histology
      showed glycogen accumulation and electron microscopy confirmed a reduction in
      myofilament density from 69.9+/-1.9% in CTRL to 57.1+/-0.9% of cell volume in HIB
      (P<0.05). In conclusion, decreased potential for force development in the
      hibernating myocardium is related to a reduction of myofibrillar protein per cell
      volume unit with replacement by glycogen and mitochondria. These changes may
      contribute to slow functional recovery on revascularization.

PMID- 17234973
TI  - Age-dependent impairment of endothelial progenitor cells is corrected by growth
      hormone-mediated increase of insulin-like growth-factor-1.
AB  - Aging is associated with an increased risk for atherosclerosis. A possible cause
      is low numbers and dysfunction of endothelial progenitor cells (EPC) which
      insufficiently repair damaged vascular walls. We hypothesized that decreased
      levels of insulin-like growth factor-1 (IGF-1) during age contribute to
      dysfunctional EPC. We measured the effect of growth hormone (GH), which increases
      endogenous IGF-1 levels, on EPC in mice and human subjects. We compared EPC
      number and function in healthy middle-aged male volunteers (57.4+/-1.4 years)
      before and after a 10 day treatment with recombinant GH (0.4 mg/d) with that of
      younger and elderly male subjects (27.5+/-0.9 and 74.1+/-0.9 years). Middle-aged
      and elderly subjects had lower circulating CD133(+)/VEGFR-2(+) EPC with impaired
      function and increased senescence. GH treatment in middle-aged subjects elevated
      IGF-1 levels (126.0+/-7.2 ng/mL versus 241.1+/-13.8 ng/mL; P<0.0001), increased
      circulating EPC with improved colony forming and migratory capacity, enhanced
      incorporation into tube-like structures, and augmented endothelial nitric oxide
      synthase expression in EPC comparable to that of the younger group. EPC
      senescence was attenuated, whereas telomerase activity was increased after GH
      treatment. Treatment of aged mice with GH (7 days) or IGF-1 increased IGF-1 and
      EPC levels and improved EPC function, whereas a two day GH treatment did not
      alter IGF-1 or EPC levels. Ex vivo treatment of EPC from elderly individuals with
      IGF-1 improved function and attenuated cellular senescence. IGF-1 stimulated EPC
      differentiation, migratory capacity and the ability to incorporate into forming
      vascular networks in vitro via the IGF-1 receptor. IGF-1 increased telomerase
      activity, endothelial nitric oxide synthase expression, phosphorylation and
      activity in EPC in a phosphoinositide-3-kinase/Akt dependent manner. Small
      interference RNA-mediated knockdown of endothelial nitric oxide synthase in EPC
      abolished the IGF-1 effects. Growth hormone-mediated increase in IGF-1 reverses
      age-related EPC dysfunction and may be a novel therapeutic strategy against
      vascular disorders with impairment of EPC.

PMID- 17234981
TI  - Previous antiplatelet treatment and mortality in patients with intracerebral
      hemorrhage.

PMID- 17234982
TI  - Sleep apnea and the risk of stroke in the elderly.

PMID- 17234983
TI  - Disparities in outcomes among patients with stroke associated with insurance
      status.
AB  - BACKGROUND AND PURPOSE: Despite well-documented discrepancies in many clinical
      conditions across insurance groups, limited research has examined insurance
      related disparities for patients with stroke. This study examined the
      relationship between insurance status and hospital care for patients with stroke.
      METHODS: Discharges with intracerebral hemorrhage and acute ischemic stroke were
      abstracted from the 2002 National Inpatient Sample. Neurologic impairment status
      and mortality were examined. RESULTS: Compared with privately insured patients,
      uninsured patients had a higher level of neurologic impairment, a longer average
      length of hospital stay, and higher mortality risk. For patients with
      intracerebral hemorrhage and acute ischemic stroke, mortality risk of uninsured
      patients was approximately 24% and 56% higher, respectively, than that of their
      privately insured peers. CONCLUSIONS: Policy should promote access to outpatient
      and preventive care for uninsured patients so risk factors such as hypertension
      can be detected and treated during early, asymptomatic stages. Further research
      is needed to evaluate the extent to which differences in outcomes are
      attributable to differences in severity level on admission.

PMID- 17234985
TI  - Albumin-induced hematocrit-lowering and B-type natriuretic peptide increase.

PMID- 17234986
TI  - Absence of usefulness of ABCD score in the early risk of stroke of transient
      ischemic attack patients.

PMID- 17234987
TI  - Confirmation of tPA treatment effect by baseline severity-adjusted end point
      reanalysis of the NINDS-tPA stroke trials.
AB  - BACKGROUND AND PURPOSE: Baseline severity-adjusted end point analysis, an
      emerging approach to the evaluation of primary end points in acute stroke trials,
      offers a novel means of adjusting trial analysis for baseline imbalances in
      presenting stroke severity among treatment groups, a factor that has complicated
      interpretation and reception of the results of the pivotal National Institute of
      Neurological Disorders and Stroke tissue plasminogen activator (NINDS-tPA)
      trials. METHODS: The sliding scale dichotomy end point responder analysis applied
      in recent acute ischemic stroke clinical trials was used to analyze NINDS-tPA
      stroke trials 1 and 2. Good outcomes were: 3-month Rankin scale=0 if pretreatment
      NIHSS scores were 1 to 7; 3-month Rankin scale=0 to 1 if pretreatment NIHSS
      scores were 8 to 14; 3-month Rankin scale=0 to 2 if pretreatment NIHSS scores
      were >14. RESULTS: Both of the NINDS-tPA stroke trials showed a statistically
      significant beneficial treatment effect of tPA. In unadjusted analyses, in trial
      1, good outcomes in tPA versus placebo patients were 39.6% versus 28.6% (odds
      ratio 1.64, P=0.049); in trial 2, 35.7% versus 24.2% (odds ratio 1.74, P=0.024).
      Among all 624 patients in trials 1 and 2 combined, good outcomes occurred in
      37.5% versus 26.3% patients (odds ratio 1.68, P=0.0034). In the 91- to 180-minute
      onset to treatment time subgroup of patients among whom baseline severity
      imbalance was particularly severe, good outcomes were noted in 36.1% versus 24.0%
      (odds ratio 1.80, P=0.021). Odds ratios favoring tPA generally further increased
      after adjustment for 12 additional covariates known to predict acute stroke
      outcome. CONCLUSIONS: Baseline-adjusted severity end point reanalysis of the
      NINDS Stroke tPA trials confirms a beneficial treatment effect of intravenous
      tPA.

PMID- 17234988
TI  - Intracranial hemorrhage associated with revascularization therapies.
AB  - BACKGROUND AND PURPOSE: This review discusses the state of our current knowledge
      on hemorrhagic transformation (HT) and summarizes key factors to be considered
      when comparing risk associated with various approaches to revascularization.
      SUMMARY OF REVIEW: HT is a common and natural consequence of infarction, likely
      related to matrix metalloproteinases and free radical pathways disrupting
      permeability barriers between blood and brain during ischemia and reperfusion.
      Symptomatic HT rates within 24 to 36 hours of stroke are increased in the setting
      of revascularization therapy regardless of modality. HT incidence rates must be
      considered in the context of the timing of imaging, the period of the study, the
      definition of clinically significant HT, and other key predictors of HT. The most
      consistently identified predictors of clinically significant HT in acute
      revascularization trials have been thrombolytic therapy, dose of lytic agents,
      edema or mass effect on head CT, stroke severity, and age. Other risk factors may
      be hyperglycemia, concurrent heparin use, timing of therapy, and timing of
      successful recanalization. Future predictors may also include imaging parameters,
      serological markers, variables related to intra-arterial technique, and arterial
      lesion location. CONCLUSIONS: Understanding how baseline and treatment variables
      impact HT rates after acute stroke is critical for those designing and
      interpreting acute stroke trials. Future trials should consider the use of PH-2
      as a standardized safety end point, putting hemorrhagic changes in the context of
      overall clinical outcome, and developing strategies to reduce the rates of
      clinically significant intracranial hemorrhage.

PMID- 17234990
TI  - Functional expression of N-formyl peptide receptors in human bone marrow-derived
      mesenchymal stem cells.
AB  - Tissue injury enhances homing and engraftment of mesenchymal stem cells (MSCs).
      However, the mechanisms by which MSCs sense the signals released by injured
      tissues and migrate toward injury sites have not been fully defined. In the
      current report, we investigated whether human MSCs express the N-formyl peptide
      receptor (FPR) and the formyl peptide receptor-like-1 (FPRL1). These receptors
      bind to N-formylated peptides by which phagocytes migrate to inflammatory sites
      and fibroblasts repopulate wounds to remodel the damaged tissues. Reverse
      transcription polymerase chain reaction (PCR) demonstrated that MSCs express both
      FPR and FPRL1 at the transcriptional level. Flow cytometric analyses revealed
      expression of both receptors at the protein level. Fusion of the enhanced green
      fluorescence protein (eGFP) to the C terminus of each receptor showed
      localization to the cell surface. Moreover, MSCs responded to stimulation by N
      formyl methionyl leucyl phenylalanine (fMLP), a prototypic N-formyl peptide,
      demonstrating rapid intracellular calcium mobilization that can be blocked by
      pertussis toxin or cyclosporin H. It is noteworthy that the fMLP-stimulated MSCs
      had an enhanced adhesion to extracellular matrix protein-coated surfaces. In
      addition, MSCs migrated toward gradients of increasing fMLP concentration,
      indicating that the receptors were functionally involved in positive chemotaxis
      to formylated peptides. Therefore, the N-formyl peptide receptors present in MSCs
      may play an important role in signaling stem cell adhesion, migration, and homing
      to injured and inflamed tissue for repair. Such a mechanism could potentially be
      exploited to direct the stem cells to target specific tissue sites, such as
      cystic fibrosis lungs, for therapy. Disclosure of potential conflicts of interest
      is found at the end of this article.

PMID- 17234989
TI  - Selection of embryonic stem cell-derived enhanced green fluorescent protein
      positive dopamine neurons using the tyrosine hydroxylase promoter is confounded
      by reporter gene expression in immature cell populations.
AB  - Transplantation of mouse embryonic stem (mES) cells can restore function in
      Parkinson disease models, but can generate teratomas. Purification of dopamine
      neurons derived from embryonic stem cells by fluorescence-activated cell sorting
      (FACS) could provide a functional cell population for transplantation while
      eliminating the risk of teratoma formation. Here we used the tyrosine hydroxylase
      (TH) promoter to drive enhanced green fluorescent protein (eGFP) expression in
      mES cells. First, we evaluated 2.5-kilobase (kb) and 9-kb TH promoter fragments
      and showed that clones generated using the 9-kb fragment produced significantly
      more eGFP+/TH+ neurons. We selected the 9-kb TH clone with the highest eGFP/TH
      overlap for further differentiation, FACS, and transplantation experiments.
      Grafts contained large numbers of eGFP+ dopamine neurons of an appropriate
      phenotype. However, there were also numerous eGFP+ cells that did not express TH
      and did not have a neuronal morphology. In addition, we found cells in the grafts
      representing all three germ layers. Based on these findings, we examined the
      expression of stem cell markers in our eGFP+ population. We found that a majority
      of eGFP+ cells were stage-specific embryonic antigen-positive (SSEA-1+) and that
      the genetically engineered clones contained more SSEA-1+ cells after
      differentiation than the original D3 mES cells. By negative selection of SSEA-1,
      we could isolate a neuronal eGFP+ population of high purity. These results
      illustrate the complexity of using genetic selection to purify mES cell-derived
      dopamine neurons and provide a comprehensive analysis of cell selection
      strategies based on tyrosine hydroxylase expression. Disclosure of potential
      conflicts of interest is found at the end of this article.

PMID- 17234991
TI  - Cyclooxygenase-2-derived prostaglandin e2 protects mouse embryonic stem cells
      from apoptosis.
AB  - Little is known about prostaglandin synthesis and function in embryonic stem
      cells. We postulated that mouse embryonic stem (mES) cells possess enzymes to
      synthesize protective prostaglandins. Compared with differentiated adult cells,
      mES cells were less susceptible to H(2)O(2)-induced apoptosis. However, their
      apoptosis was enhanced by indomethacin or SC-236, a selective inhibitor of
      cyclooxygenase (COX)-2. Analysis of COX pathway enzymes by Western blotting
      revealed expression of COX-2 and cytosolic and microsomal prostaglandin E(2)
      (PGE(2)) synthases. COX-1 and prostacyclin (PGI(2)) synthases were undetectable.
      mES cells produced PGE(2) but not PGI(2). Importantly, PGE(2) rescued mES cells
      from apoptosis. To elucidate the signaling mechanism by which PGE(2) inhibits
      apoptosis, we analyzed E-type prostaglandin (EP) receptors by Western blots. All
      EP isoforms were detected except EP4. Butaprost, a specific EP2 agonist, rescued
      mES cells from apoptosis, whereas sulprostone, an EP1/EP3 agonist, had no effect,
      suggesting selective interaction of PGE(2) with EP2. The antiapoptotic effect of
      PGE(2) was abrogated by Ly-294002 or wortmannin but not H-89 or a specific
      inhibitor of protein kinase A, suggesting signaling via phosphatidylinositol-3
      kinase (PI-3K). Akt was constitutively active in mES cells, which were inhibited
      by indomethacin and rescued by PGE(2). The rescuing effect of PGE(2) was
      abrogated by Ly-294002. These results indicate that mES cells constitutively
      express COX-2 and PGE synthases and produce PGE(2), which confers resistance to
      apoptosis via EP2-mediated activation of PI-3K to the Akt pathway. Disclosure of
      potential conflicts of interest is found at the end of this article.

PMID- 17234993
TI  - Tethered epidermal growth factor provides a survival advantage to mesenchymal
      stem cells.
AB  - MSC can act as a pluripotent source of reparative cells during injury and
      therefore have great potential in regenerative medicine and tissue engineering.
      However, the response of MSC to many growth factors and cytokines is unknown.
      Many envisioned applications of MSC, such as treating large defects in bone,
      involve in vivo implantation of MSC attached to a scaffold, a process that
      creates an acute inflammatory environment that may be hostile to MSC survival.
      Here, we investigated cellular responses of MSC on a biomaterial surface
      covalently modified with epidermal growth factor (EGF). We found that surface
      tethered EGF promotes both cell spreading and survival more strongly than
      saturating concentrations of soluble EGF. By sustaining mitogen-activated protein
      kinase kinase-extracellular-regulated kinase signaling, tethered EGF increases
      the contact of MSC with an otherwise moderately adhesive synthetic polymer and
      confers resistance to cell death induced by the proinflammatory cytokine, Fas
      ligand. We concluded that tethered EGF may offer a protective advantage to MSC in
      vivo during acute inflammatory reactions to tissue engineering scaffolds. The
      tethered EGF-modified polymers described here could be used together with
      structural materials to construct MSC scaffolds for the treatment of hard-tissue
      lesions, such as large bony defects. Disclosure of potential conflicts of
      interest is found at the end of this article.

PMID- 17234995
TI  - Cardiovascular MR imaging in neonates and infants with congenital heart disease.
AB  - Cardiovascular magnetic resonance (MR) imaging has become an important
      alternative to echocardiography and angiocardiography in the evaluation of
      patients with congenital heart disease (CHD). It is increasingly being used in
      neonates and infants for the initial investigation of CHD or as follow-up after
      surgery or catheter-guided intervention. Specific indications for cardiovascular
      MR imaging in neonates and infants include investigation of the thoracic
      vasculature, quantification of the ventricular volumes, and evaluation of primary
      cardiac tumors. To obtain good-quality MR images in neonates and infants, it is
      essential to adjust the technical parameters of the pulse sequences to the small
      size and fast heart rates of the patients. Various MR imaging techniques are
      available that are effective in demonstrating the complex morphologic features of
      the cardiovascular system and that provide additional functional and hemodynamic
      information. The information provided by cardiovascular MR imaging is useful for
      treatment planning and, in many cases, may obviate potentially harmful cardiac
      catheterization.

PMID- 17234994
TI  - Generation of functional dopamine neurons from neural precursor cells isolated
      from the subventricular zone and white matter of the adult rat brain using Nurr1
      overexpression.
AB  - Neural precursor (NP) cells from adult mammalian brains can be isolated, expanded
      in vitro, and potentially used as cell replacement source material for treatment
      of intractable brain disorders. Reduced ethical concerns, lack of teratoma
      formation, and possible ex vivo autologous transplantation are critical
      advantages to using adult NP donor cells over cells from fetal brain tissue or
      embryonic stem cells. However, the usage of adult NP cells is limited by the
      ability to induce specific neurochemical phenotypes in these cells. Here, we
      demonstrate induction of a dopaminergic phenotype in NP cells isolated from the
      subventricular zone (SVZ) and white matter of rodent adult brains using
      overexpression of the nuclear receptor Nurr1 in vitro. Forced expression of
      Nurr1, a transcriptional factor specific to midbrain dopamine (DA) neuron
      development, caused in the adult cells an acquisition of the DA neurotransmitter
      phenotype and sufficient differentiation toward morphologically, phenotypically,
      and ultrastructurally mature DA neurons. Co-expression of neurogenic factor Mash1
      and treatment with neurogenic cytokines brain-derived neurotrophic factor and
      neurotrophin-3 greatly enhanced Nurr1-induced DA neuron yield. The Nurr1-induced
      DA neurons demonstrated in vitro presynaptic DA neuronal functionality, releasing
      DA neurotransmitter in response to depolarization stimuli and specific DA
      reuptake. Furthermore, Nurr1-engineered adult SVZ NP cells survived, integrated,
      and differentiated into DA neurons in vivo that can reverse the behavioral
      deficit in the host striatum of parkinsonian rats. These findings open the
      possibility for the use of precursor cells from adult brains as a cell source for
      neuronal replacement treatment of Parkinson disease. Disclosure of potential
      conflicts of interest is found at the end of this article.

PMID- 17234996
TI  - Lesions of the cardiophrenic space: findings at cross-sectional imaging.
AB  - Cross-sectional imaging techniques allow excellent visualization of the
      cardiophrenic space. Under normal conditions, the cardiophrenic space is occupied
      by fat, the amount of which is usually increased in overweight individuals. It
      has been suggested that this fat accumulation correlates with the risk of
      cardiovascular disease. Several alterations originating above or below the
      diaphragm can affect the cardiophrenic space. Inflammatory lesions such as
      pericardial fat necrosis and tumoral masses are sometimes seen. Lymphoma is a
      major but not exclusive cause of cardiophrenic adenopathy and must be
      differentiated from lymphatic seeding of supradiaphragmatic and
      infradiaphragmatic malignancies. In patients with portal hypertension,
      cardiophrenic space varices are not uncommon. Other masses or pseudomasses
      occurring in this region include pericardial cysts, mediastinal tumors, and
      diaphragmatic hernia. Computed tomography and magnetic resonance imaging of the
      thorax are helpful in characterizing cardiophrenic lesions initially identified
      at plain radiography. Such characterization helps narrow the differential
      diagnosis when lesions are detected in this location.

PMID- 17234997
TI  - Lines and stripes: where did they go?--From conventional radiography to CT.
AB  - Frontal and lateral radiography has traditionally been used to evaluate the
      chest, although computed tomography (CT) and high-resolution CT are increasingly
      being used as an adjunct to conventional radiography for the evaluation of
      parenchymal and mediastinal disease. Nevertheless, radiography remains a very
      important modality in this context, and use of chest radiography alone can
      provide a vast amount of useful information. This information is derived from the
      configurations and interrelationships of the anatomic structures in the lung,
      mediastinum, and pleura and forms the basis of the "lines and stripes" concept,
      which plays a valuable role in establishing a diagnosis before proceeding to CT.
      The inability to recognize that a chest radiograph is abnormal owing to
      displacement of one of these lines or stripes may lead to failure to request a
      potentially valuable CT examination. Radiologists must be familiar with the
      anatomic basis of these mediastinal lines and stripes and be able to recognize
      their normal and abnormal appearances. In this way, they can develop an
      appropriate differential diagnosis prior to obtaining additional information with
      chest CT.

PMID- 17234998
TI  - Price of isotropy in multidetector CT.
AB  - Recent advances in multidetector computed tomography (CT) have made isotropic
      data acquisition feasible for nearly every application. The benefits of routine
      use of isotropic data for image display and interpretation have been described in
      the literature and at educational conferences. However, there is usually a trade
      off in the form of an increased radiation dose to the patient. The parameters
      that affect the radiation dose vary considerably in accordance with the CT
      scanner design, and those variations determine the cost in dose increase relative
      to the voxel size. The detector configuration and beam collimation (narrow or
      wide) used for a particular acquisition also affect the voxel size and the
      relationship between spatial resolution and the radiation dose. By closely
      comparing the quality of multidetector CT images obtained with different detector
      configurations on scanners with four, 16, 40, and 64 channels and the estimated
      radiation exposure incurred with each option, radiologists may achieve an
      understanding of the relationship between radiation dose and voxel size. This
      understanding, in turn, may help balance the need for diagnostic image quality
      against the concern for patient safety.

PMID- 17234999
TI  - Functional MR imaging of prostate cancer.
AB  - T2-weighted magnetic resonance (MR) imaging has been widely used for pretreatment
      work-up for prostate cancer, but its accuracy for the detection and localization
      of prostate cancer is unsatisfactory. To improve the utility of MR imaging for
      diagnostic evaluation, various other techniques may be used. Dynamic contrast
      material-enhanced MR imaging allows an assessment of parameters that are useful
      for differentiating cancer from normal tissue. The advantages of this technique
      include the direct depiction of tumor vascularity and, possibly, obviation of an
      endorectal coil; however, there also are disadvantages, such as limited
      visibility of cancer in the transitional zone. Diffusion-weighted imaging
      demonstrates the restriction of diffusion and the reduction of apparent diffusion
      coefficient values in cancerous tissue. This technique allows short acquisition
      time and provides high contrast resolution between cancer and normal tissue, but
      individual variability in apparent diffusion coefficient values may erode
      diagnostic performance. The accuracy of MR spectroscopy, which depicts a higher
      ratio of choline and creatine to citrate in cancerous tissue than in normal
      tissue, is generally accepted. The technique also allows detection of prostate
      cancer in the transitional zone. However, it requires a long acquisition time,
      does not directly depict the periprostatic area, and frequently is affected by
      artifacts. Thus, a comprehensive evaluation in which both functional and anatomic
      MR imaging techniques are used with an understanding of their particular
      advantages and disadvantages may help improve the accuracy of MR for detection
      and localization of prostate cancer.

PMID- 17235000
TI  - Missed breast cancers at US-guided core needle biopsy: how to reduce them.
AB  - Ultrasonographically (US) guided core needle biopsy is currently recognized as a
      reliable alternative to surgical biopsy for the histopathologic diagnosis of
      breast lesions. However, despite advances in biopsy devices and techniques, false
      negative diagnoses are unavoidable and may delay the diagnosis and treatment of
      breast cancer. The most common reasons for false-negative diagnosis are (a)
      technical or sampling errors, (b) failure to recognize or act on radiologic
      histologic discordance, and (c) lack of imaging follow-up after a benign biopsy
      result. Technical difficulties (eg, poor lesion or needle visualization, deeply
      located lesions, dense fibrotic tissue) cause inaccurate sampling but can be
      reduced by using modified standard techniques. Radiologic-histologic correlation
      is also of critical importance in US-guided core needle biopsy. Radiologic
      histologic discordance occurs when the histologic results do not provide a
      sufficient explanation for the imaging features and indicates that the lesion may
      not have been sampled adequately, so that repeat biopsy is warranted. Appropriate
      follow-up imaging is invaluable; even patients with concordant benign findings
      after US-guided core needle biopsy are directed to undergo follow-up imaging
      because there may be delays in the recognition of false-negative findings.
      Optimization of technique, radiologic-histologic correlation, and postbiopsy
      follow-up protocols are recommended to reduce the occurrence of false-negative
      diagnosis at US-guided core needle biopsy performed by radiologists.

PMID- 17235001
TI  - Imaging of neurologic disorders associated with pregnancy and the postpartum
      period.
AB  - Diverse pathologic conditions affect the central nervous system (CNS) and
      pituitary gland during pregnancy and the puerperium. Some are specific to the
      physiologic process of reproduction (eg, eclampsia, postpartum cerebral
      angiopathy, Sheehan syndrome, lymphocytic adenohypophysitis). Others are
      nonspecific but occur more often in pregnant women (eg, cerebral infarction,
      dural venous thrombosis, pituitary apoplexy). Recognition of the characteristic
      imaging findings in eclampsia, for example, may allow exclusion of other
      disorders. Even when imaging changes are nonspecific, knowledge of those entities
      associated with pregnancy and awareness of the increased likelihood of certain
      diseases in pregnancy will allow a more informed differential diagnosis.
      Differentiation of primary nonaneurysmal subarachnoid hemorrhage (SAH) from
      aneurysmal SAH is an example. Moreover, earlier use of imaging will result in
      fewer delayed diagnoses. For example, magnetic resonance venography allows early
      diagnosis of cerebral venous thrombosis. Even when the imaging changes are less
      specific, knowledge of likely possibilities will lead to more appropriate earlier
      use of imaging. For example, the stimulatory effects of pregnancy on
      prolactinoma, meningioma, hemangioblastoma, vestibular schwannoma, and metastatic
      tumors such as breast cancer and choriocarcinoma suggest the early use of CNS
      imaging to avoid the consequences of a delayed diagnosis.

PMID- 17235002
TI  - Blood in the belly: CT findings of hemoperitoneum.
AB  - Hemoperitoneum may occur in various emergent conditions. In the trauma setting,
      evidence of intraperitoneal blood depicted at computed tomography (CT) should
      lead the radiologist to conduct a careful search of images for the injured
      visceral organ (the liver or spleen). Specific CT signs, such as a sentinel clot
      or extravasation of intravascular contrast material, may indicate the source of
      bleeding and help direct management. In addition, the configuration of
      accumulated blood may help identify the injured organ; for example, triangular
      fluid collections are observed in the mesentery most often in the setting of
      bowel or mesenteric injury. Less commonly, hemoperitoneum may have a nontraumatic
      origin. Iatrogenic hemoperitoneum may occur as a complication of surgery or other
      interventional procedures in the abdominal cavity or as a result of
      anticoagulation therapy. Hemoperitoneum also may be seen in the setting of blood
      dyscrasias such as hemophilia and polycythemia vera. Tumor-associated hemorrhage,
      which most often occurs in hepatocellular carcinoma, hepatic adenoma, or vascular
      metastatic disease, also may produce hemoperitoneum. Other potential causes of
      nontraumatic hemoperitoneum are gynecologic conditions such as hemorrhage or
      rupture of an ovarian cyst and rupture of the gestational sac in ectopic
      pregnancy, and hepatic hematoma in syndromic hemolysis with elevated liver
      enzymes and low platelet count (HELLP syndrome). Vascular lesions (visceral
      artery aneurysms and pseudoaneurysms) that occur in systemic vascular diseases
      such as Ehlers-Danlos syndrome or in pancreatitis are another less common source
      of hemoperitoneum.

PMID- 17235003
TI  - The perihepatic space: comprehensive anatomy and CT features of pathologic
      conditions.
AB  - The liver is covered by visceral peritoneum except at the bare area, bed of the
      gallbladder, and porta hepatis. The investing peritoneum becomes contiguous with
      the adjacent structures such as the diaphragmatic peritoneum, lesser omentum, and
      ligamentum teres. An inflammatory process or tumors involving the perihepatic
      space are usually affected by intraperitoneal flow dynamics, which depend on the
      anatomy of the recess as well as gravity and negative subdiaphragmatic pressure.
      Pathologic conditions that occur in the perihepatic space include abnormal air,
      fatty masses, conditions producing fluid attenuation at computed tomography (CT),
      and soft-tissue masses. Enhancement of the hepatic capsule indicates
      inflammation, as is seen in Fitz-Hugh-Curtis syndrome. The perihepatic ligaments
      may be invaded by various conditions by means of direct invasion, subperitoneal
      extension, or extension along the lymphatic vessels. Knowledge of the normal
      anatomy of the perihepatic space together with the clinical history and
      characteristic features at CT can assist the radiologist in making the correct
      diagnosis.

PMID- 17235004
TI  - Bowel hot spots at PET-CT.
AB  - Positron emission tomography (PET) with 2-[fluorine-18]fluoro-2-deoxy-d-glucose
      (FDG) has been shown to be sensitive in the detection of many bowel malignancies,
      but its specificity is lower because of various physiologic and pathologic
      patterns of bowel FDG uptake. PET-computed tomography (CT) can be useful in
      localizing and characterizing foci of increased FDG uptake within the bowel. As
      the use of PET-CT in the staging and monitoring of oncologic disease continues to
      expand, familiarity with these patterns of bowel FDG uptake is essential and can
      help determine the need for and the relative urgency of further testing. Although
      a variety of imaging protocols are used for PET-CT, the use of negative oral
      contrast agent allows improved bowel distention while eliminating potential
      artifacts caused by high-density oral contrast agents. In addition, correlation
      with the CT portion of the combined PET-CT examination can sometimes help
      identify the cause of focal or segmental bowel uptake. The radiologist should be
      aware of potential pitfalls in the evaluation of FDG-avid foci within the
      abdomen, including bowel motility and low-attenuation lesions mimicking bowel.
      Nevertheless, even though the precise role of combined PET-CT for bowel
      assessment has yet to be determined, the application of sound basic principles of
      image interpretation will help ensure the accurate interpretation of bowel
      findings seen with this combined modality.

PMID- 17235005
TI  - Scrub typhus: clinical, pathologic, and imaging findings.
AB  - Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi. The
      main pathologic change is focal or disseminated vasculitis caused by the
      destruction of endothelial cells and the perivascular infiltration of leukocytes.
      The diagnosis of scrub typhus is based on the patient's history of exposure,
      clinical features, and results of serologic testing. Regional and generalized
      lymphadenopathy is common. The pulmonary manifestations of scrub typhus include
      interstitial pneumonia, interstitial edema, and hemorrhage caused by vasculitis.
      Abdominal manifestations include splenomegaly, periportal edema, gallbladder wall
      thickening, and lymphadenopathy. Although the severity of scrub typhus varies
      considerably, involvement of the central nervous system is seen in almost all
      patients and can result in meningoencephalitis. A high degree of clinical
      suspicion and familiarity with the various radiologic manifestations of scrub
      typhus allow early diagnosis and timely initiation of appropriate therapy, and
      thereby may help reduce patient morbidity.

PMID- 17235006
TI  - Pathologic and MR imaging features of benign fibrous soft-tissue tumors in
      adults.
AB  - Benign fibrous (fibroblastic or myofibroblastic) soft-tissue tumors are a
      heterogeneous group of fibrous lesions with widely varied anatomic locations,
      biologic behavior, and pathologic features. The four broad categories of fibrous
      proliferation are benign fibrous proliferations, fibromatoses, fibrosarcomas, and
      fibrous proliferations of infancy and childhood. The first two categories include
      nonaggressive fibroblastic lesions such as nodular fasciitis, as well as
      fibromatoses that demonstrate more aggressive biologic behavior (eg, desmoid
      tumors). In adults, fibrous tumors are among the most common soft-tissue lesions
      encountered in clinical practice. MR imaging can be useful for defining the
      intrinsic signal characteristics, size, and compartmental extension of these
      lesions. Histologic features of the tumor also may be depicted on T2-weighted MR
      images. Hypocellular fibrous tumors with dense collagenous components tend to
      have lower signal intensity on T2-weighted images than do lesions that are more
      cellular or that contain greater amounts of extracellular myxoid matrix. When
      interpreting MR images of soft-tissue masses in adults, radiologists should be
      aware of the clinical behavior, common sites of occurrence, and histopathologic
      and imaging features of the common benign fibrous soft-tissue tumors.

PMID- 17235007
TI  - Anatomically based guidelines for core needle biopsy of bone tumors: implications
      for limb-sparing surgery.
AB  - Diagnostic image-guided needle biopsy plays a vital role in the work-up and
      treatment of patients with extremity bone tumors. The radiologist and the
      orthopedic oncologic surgeon should take a team approach to this procedure,
      especially when the bone lesion might be a primary sarcoma for which limb-sparing
      surgery (LSS) would be considered. A set of anatomically based guidelines were
      developed that can be used by the radiologist, in combination with case-by-case
      consultation with the surgeon, to plan image-guided core needle biopsies of
      extremity long bone lesions that may be treatable with LSS. By using these
      guidelines, along with the aforementioned consultation, the radiologist will be
      able to preserve the patient's chances of receiving optimal surgical treatment.

PMID- 17235008
TI  - Postoperative evaluation of the knee after autologous chondrocyte implantation:
      what radiologists need to know.
AB  - Articular cartilage lesions occur commonly. Cartilage is relatively avascular and
      is unable to self-repair. A chondral lesion may become symptomatic. It may lead
      to osteoarthritis and increased morbidity. The aim of cartilage repair is to
      restore hyaline cartilage. There are many types of cartilage repair surgery, most
      of which result in fibrocartilage repair tissue that is suboptimal. Autologous
      chondrocyte implantation has been shown to produce hyaline-type repair tissue.
      Magnetic resonance (MR) imaging is performed preoperatively to define the ulcer
      and postoperatively to evaluate the technical success of implantation and the
      state of cartilage healing and to identify potential complications. Features of
      the autologous chondrocyte implantation graft that are assessed include the
      degree of filling by repair tissue, its integration with native cartilage and
      subchondral bone, the character of the graft substance and surface, and the
      underlying bone. MR arthrography is superior to unenhanced MR imaging because
      intraarticular contrast material allows the recipient site to be physically
      separated from adjacent structures so that it can be characterized more
      accurately. MR imaging and arthroscopy are complementary investigations in the
      follow-up of an autologous chondrocyte implantation in the knee. The appearance
      of the knee after autologous chondrocyte implantation varies among individuals
      and according to the time-course of healing. Familiarity with the surgical
      procedure and imaging appearance is essential for an accurate postsurgical
      assessment.

PMID- 17235010
TI  - From the archives of the AFIP: Gastrointestinal carcinoids: imaging features with
      clinicopathologic comparison.
AB  - Gastrointestinal carcinoids are well-differentiated endocrine neoplasms that
      belong to a diverse group of tumors that arise from cells of the diffuse
      endocrine system. A wide variety of specialized endocrine cells that populate the
      gastrointestinal mucosa and submucosa give rise to carcinoids. Consequently,
      carcinoids may occur throughout the gastrointestinal tract and produce a variety
      of hormones and protein products that are associated with specific clinical
      symptoms. Biologic behavior of carcinoids varies by site and cell type, but all
      gastrointestinal carcinoids are considered to have malignant potential. They may
      produce specific syndromes such as Zollinger-Ellison syndrome, or they may occur
      in association with inherited syndromes such as multiple endocrine neoplasia type
      1 or neurofibromatosis type 1. Metastatic carcinoids may produce carcinoid
      syndrome. The small intestine is the most common location for gastrointestinal
      carcinoids. Most small intestinal carcinoids arise from enterochromaffin cells of
      the distal ileum that produce serotonin. Small intestinal carcinoids often have
      an aggressive biologic behavior and, as such, patients frequently have metastases
      to regional lymph nodes and the liver at initial presentation. Pathologic and
      radiologic manifestations of serotonin-producing small intestinal carcinoids are
      related to local and regional effects of serotonin and its metabolites. In
      contrast, carcinoids of the appendix and rectum are commonly discovered
      incidentally as small lesions that are unassociated with clinical evidence of
      hormone production and have a more indolent clinical course. Carcinoids of the
      stomach, duodenum, and colon are uncommon but have distinctive clinical,
      pathologic, and radiologic appearances. Knowledge of the diverse clinical,
      pathologic, and radiologic spectrum of gastrointestinal carcinoids is important
      in the imaging and management of patients with suspected carcinoids or focal
      gastrointestinal masses.

PMID- 17235009
TI  - Radiologic assessment of reverse shoulder arthroplasty.
AB  - The reverse shoulder prosthesis was approved for clinical use in the United
      States in March 2004. This new prosthesis reverses the normal ball-and-socket
      relationship of the shoulder joint. As a result of replacement of the glenoid
      component with a ball and of the humeral head with a socket, the center of
      rotation is moved distally and medially, allowing more control of shoulder motion
      by the deltoid muscle. This improved geometric configuration allows shoulder
      reconstruction in patients who have irreparable rotator cuff damage with
      secondary arthropathy, pain, and "pseudoparalysis" (ie, inability to lift the arm
      above the horizontal). Patients experience a significant improvement in range of
      motion and markedly decreased pain after undergoing reverse shoulder
      arthroplasty; however, the procedure is associated with a relatively high rate of
      complications, including dislocation, infection, loosening, malpositioning of the
      glenoid component or fixation screws, disassembly of the humeral component,
      periprosthetic fracture, and inferior glenoid impingement leading to scapular
      erosion. Therefore, it is important that the radiologist be familiar with the
      normal and abnormal imaging appearances of this new prosthesis.

PMID- 17235011
TI  - Best cases from the AFIP: Malignant mesothelioma.

PMID- 17235012
TI  - Best cases from the AFIP: Pulmonary Langerhans cell histiocytosis.

PMID- 17235015
TI  - Evaluation of birth and weaning traits of Romosinuano calves as purebreds and
      crosses with Brahman and Angus.
AB  - The objectives of this work were to evaluate birth and weaning traits, to
      estimate genetic effects, including heterosis and direct and maternal breed
      effects, and to evaluate calving difficulty, calf vigor at birth, and calf
      mortality of Romosinuano as purebreds and as crosses with Brahman and Angus.
      Calves (n = 1,348) were spring-born from 2002 through 2005 and weaned in the fall
      of each year at about 7 mo of age. Traits evaluated included birth and weaning
      weight, ADG, BCS, and weaning hip height. Models used to analyze these traits
      included the fixed effects of year, sire and dam breeds, management unit, calf
      sex, cow age, and source of Angus sire (within or outside of the research herd).
      Calf age in days was investigated as a covariate for weaning traits. Sire within
      sire breed and dam within dam breed were random effects. Estimates of Romosinuano
      Brahman and Romosinuano-Angus heterosis (P < 0.05) were 2.6 +/- 0.3 (8.6%) and
      1.4 +/- 0.3 kg (4.7%) for birth weight, 20.5 +/- 1.5 (9.5%) and 14.6 +/- 1.4 kg
      (7.4%) for weaning weight, 79.2 +/- 6.1 (9.8%) and 55.1 +/- 6.0 g (7.5%) for ADG,
      0.16 +/- 0.03 (2.7%) and 0.07 +/- 0.03 (1.2%) for BCS, and 2.77 +/- 0.32 cm
      (2.4%) and 1.87 +/- 0.32 cm (1.7%) for hip height. Heterosis for Brahman-Angus
      was greater (P < 0.05) than all Romosinuano estimates except those for
      Romosinuano-Brahman and Romosinuano-Angus BCS. Romosinuano direct effects were
      negative and lowest of the breeds, except for the Angus estimate for hip height.
      Romosinuano maternal effects were the largest of the 3 breeds for birth weight
      and hip height but intermediate to the other breeds for weaning weight and ADG. A
      large proportion of Brahman-sired calves from Angus dams (0.09 +/- 0.03; n = 11)
      was born in difficult births and died before 4 d of age. Brahman and Angus
      purebreds and Romosinuano-sired calves from Brahman dams also had large
      proportions of calves that died before weaning (0.09 or greater). Results
      indicated that Romosinuano may be used as a source of adaptation to subtropical
      environments and still incorporate substantial crossbred advantage for weaning
      traits, although not to the extent of crosses of Brahman and Angus.

PMID- 17235013
TI  - Informatics in radiology: use of the MIRC DICOM service for clinical trials to
      automatically create teaching file cases from PACS.
AB  - The Medical Imaging Resource Center (MIRC) software of the Radiological Society
      of North America is used to share teaching files and clinical trial data. By
      using the MIRC service for clinical trials, teaching file cases can be
      automatically generated directly from picture archiving and communication systems
      (PACS). The advantage of using the clinical trials service over the authoring
      service is the need for minimal user intervention, because data already present
      in the Digital Imaging and Communications in Medicine (DICOM) header can be
      automatically inserted into teaching file cases. When reading a case on the PACS
      workstation, the radiologist needs only to select the images for the teaching
      file case, write the diagnosis in the "Study Comments" box (usually used for
      "wet" readings), and send the case to the MIRC server directly from the
      workstation. The MIRC server automatically makes the images anonymous and fills
      in the modified teaching file template by using the data in the DICOM header
      (patient age, patient sex, clinical history, diagnosis, imaging modality, organ
      system), thus creating a simple teaching file. If desired, the teaching file case
      can be edited at a later time. By making minor modifications to the MIRC DICOM
      clinical trials service, it is possible to create teaching file cases with
      minimal effort. Supplemental material available at
      radiographics.rsnajnls.org/cgi/content/full/27/1/269/DC1.

PMID- 17235016
TI  - Inbreeding trend and inbreeding depression in the Danish populations of Texel,
      Shropshire, and Oxford Down.
AB  - The objective of this study was to analyze the development of inbreeding and
      estimate inbreeding depression in the Danish populations of 3 major meat type
      sheep breeds. The pedigrees contained 29,336 Texel, 22,838 Shropshire, and 11,487
      Oxford Down. The rate of inbreeding was approximately 1% per generation for all
      breeds, but the rate of increase in co-ancestry was somewhat lower (0.45 to
      0.71), indicating that more inbreeding has been accumulating than would be
      expected if mating was at random. Inbreeding depression for birth weight, ADG
      from birth until 2 mo, and litter size was estimated for all 3 breeds using a
      minimum of 15,000 records per trait and breed. All traits showed depression due
      to inbreeding of the animal itself. For most combinations of trait and breed,
      there was also a significant reduction of the phenotype due to inbreeding in the
      dam. The size of inbreeding depression was 1.2 to 2.6% of the mean, resulting in
      an increase in the inbreeding coefficient of the individual of 0.10, and
      estimates were similar for similar increases in maternal inbreeding. The rate of
      inbreeding in these breeds needs to be reduced in the future to avoid a further
      decline in birth weight, ADG, and litter size.

PMID- 17235017
TI  - Three statistical approaches for genetic analysis of disease resistance to
      vibriosis in Atlantic cod (Gadus morhua L.).
AB  - The objective of this study was to estimate and compare variance components and
      sire breeding values for disease resistance to vibriosis in Atlantic cod (Gadus
      morhua L.) using 3 statistical approaches. A total of 3,576 individually tagged
      juvenile cod from 50 full-sib families were infected with Vibrio anguillarum,
      which causes vibriosis, a frequently reported disease in cod aquaculture. The
      experimental fish were progeny of captured wild cod from populations of southern
      coastal cod (POP1), and northern coastal cod and northeast Arctic cod (combined
      as POP2 in the genetic analyses). Fish were randomly assigned to 1 of 3 test
      tanks, and daily mortality was recorded until the termination of the experiment
      at d 31 postinfection. Variance components were estimated separately for the 2
      populations using a Cox regression model, univariate linear model, and a linear
      model that accounted for censoring. With all approaches, the additive genetic
      sire variance estimated from POP1 was greater than for POP2. Heritability
      estimates across populations varied from 0.08 to 0.17 depending on the method
      used. The Cox regression model and univariate linear model resulted in greater
      heritability estimates for POP1 (0.10 and 0.16) than for POP2 (0.08 and 0.13),
      whereas the contrary was true with a linear model that accounted for censoring
      (0.17 vs. 0.14). The predicted breeding values for the sires from the 3
      approaches were highly correlated (0.97 to 0.99). This is likely due to the fact
      that censoring only occurred at the end of the test; i.e., observations of the
      most resistant fish were censored. The considerable genetic variation found in
      this study suggests that vibriosis resistance may be improved through selective
      breeding. The univariate linear model, even without censoring of the data, was
      robust for the estimation of breeding values using the present data. Therefore,
      inclusion of vibriosis resistance in the multivariate linear estimation of
      breeding values for the traits of economic importance in Atlantic cod seems
      appropriate.

PMID- 17235018
TI  - Genetic parameters for EUROP carcass traits within different groups of cattle in
      Ireland.
AB  - The first objective of this study was to test the ability of systems of weighing
      and classifying bovine carcasses used in commercial abattoirs in Ireland to
      provide information that can be used for the purposes of genetic evaluation of
      carcass weight, carcass fatness class, and carcass conformation class. Secondly,
      the study aimed to test whether genetic and phenotypic variances differed by
      breed of sire. Variance components for carcass traits were estimated for crosses
      between dairy cows and 8 breeds of sire commonly found in the Irish cattle
      population. These 8 breeds were Aberdeen Angus, Belgian Blue, Charolais,
      Friesian, Hereford, Holstein, Limousin, and Simmental. A multivariate animal
      model was used to estimate genetic parameters within the Holstein sire breed
      group. Univariate analyses were used to estimate variance components for the
      remaining 7 sire breed groups. Multivariate sire models were used to formally
      test differences in genetic variances in sire breed groups. Field data on 64,443
      animals, which were slaughtered in commercial abattoirs between the ages of 300
      and 875 d, were analyzed in 8 analyses. Carcass fat class and carcass
      conformation class were measured using the European Union beef carcass
      classification system (EUROP) scale. For all 3 traits, the sire breed group with
      the greatest genetic variance had a value of more than 8 times the sire breed
      group with least genetic variance. Heritabilities ranged from zero to moderate
      for carcass fatness class (0.00 to 0.40), from low to moderate for carcass
      conformation class (0.04 to 0.36), and from low to high for carcass weight (0.06
      to 0.65). Carcass weight was the most heritable (0.26) of the 3 traits. Carcass
      conformation class and carcass fatness class were equally heritable (0.17).
      Genetic and phenotypic correlations were all positive in the Holstein sire breed
      group. The genetic correlations varied from 0.11 for the relationship between
      carcass weight and carcass fatness class to 0.44 for the relationship between
      carcass conformation class and carcass fatness class. Carcass weight and
      classification data collected in Irish abattoirs are useful for the purposes of
      genetic evaluation for beef traits of Irish cattle. There were significantly
      different variance components across the sire breed groups.

PMID- 17235019
TI  - Genetic relationships between growth and carcass traits and profitability in
      Japanese Brown cattle.
AB  - The objectives of this study were 1) to examine the genetic relationship between
      growth and carcass traits and carcass price (CaP) and profitability in Japanese
      Brown cattle, 2) to estimate economic values of carcass and growth traits as
      regression coefficients of price and profit traits on growth and carcass traits
      using a multiple regression model, and 3) to compare direct and indirect
      predictions of the genetic merit of profit obtained from multitrait analysis and
      selection index, respectively. Growth and carcass traits considered in this study
      were ADG during the feedlot period, CWT, LM area (LMA), rib thickness (RT),
      subcutaneous fat thickness (SFT), and marbling score (MS). Carcass price was
      evaluated as a price trait independent of its influence on profit. Profit traits
      were defined as 1) net income per year (PROF1), 2) net income per year/energy
      requirement (PROF2), and 3) net income per year minus feed costs (PROF3).
      Correlations between direct and indirect predictions were estimated based on EBV
      of sires and dams with progeny records. The heritability estimate for CaP was
      0.41. The heritability estimates for profit traits were high and were 0.62, 0.66,
      and 0.60 for PROF1, PROF2, and PROF3, respectively. The genetic correlations
      between CaP and ADG, CWT, LMA, RT, SFT, and MS were 0.19, 0.14, 0.30, 0.38, 
      0.11, and 0.98, respectively. Among the profit traits, PROF1 had the greatest
      genetic correlations with growth and carcass traits. The correlations with ADG,
      CWT, LMA, RT, SFT, and MS were 0.30, 0.21, 0.24, 0.39, -0.01, and 0.69,
      respectively. These estimates indicate that use of profit traits as a selection
      criterion may promote desirable correlated responses in growth and carcass
      traits. The economic values for growth and carcass traits estimated relative to
      CaP and each profit trait differed because of the apparent differences in the
      description of these traits. The correlations between EBV for the same profit
      traits from direct and indirect predictions were high and ranged from 0.818 to
      0.846 based on EBV of sires and from 0.786 to 0.798 based on EBV of dams. The
      strong correlations between direct and indirect predictions for profit indicate
      that there is no advantage to selecting directly for profit compared with an
      index with all of the component traits.

PMID- 17235020
TI  - Direct responses to six generations of selection for ovulation rate or prenatal
      survival in Large White pigs.
AB  - Effects of selection for ovulation rate or prenatal survival were examined using
      data from 3 pigs lines derived from the same base Large White population. Two
      lines were selected for 6 generations on high ovulation rate at puberty (OR line)
      or high prenatal survival corrected for ovulation rate in the first 2 parities
      (PS line). The third line was an unselected control line. Genetic parameters for
      ovulation rate on the left, right, and both ovaries at puberty (ORPL, ORPR, and
      ORP, respectively) and at fertilization (ORFL, ORFR, and ORF, respectively),
      total number of piglets born (TNB) per litter, prenatal survival (PS = TNB/ORF),
      and PS corrected for ovulation rate (CPS = PS + 0.018ORF) were estimated using
      REML methodology. Responses to selection were estimated by computing differences
      between OR or PS and control lines at each generation using least squares and
      mixed models methodology. Average genetic trends were computed by regressing line
      differences on generation number. Realized heritabilities were estimated using
      standard procedures. Heritability estimates were 0.17, 0.11, 0.34, 0.13, 0.09,
      0.33, 0.14, 0.11, and 0.17 (SE = 0.01 to 0.03) for ORPL, ORPR, ORP, ORFL, ORFR,
      ORF, PS, CPS, and TNB, respectively. Realized heritabilities were 0.37 +/- 0.08
      and 0.10 +/- 0.09 for ORP and CPS, respectively. The different measures of
      ovulation rate had strong genetic correlations (r(g) > 0.7). The ORF had midrange
      negative genetic correlations with PS and CPS (-0.45 +/- 0.07 and -0.42 +/- 0.08,
      respectively). The ORP also had an antagonistic genetic relationship with PS (
      0.26 +/- 0.07) but was almost independent from CPS (-0.02 +/- 0.11). The TNB was
      moderately correlated with ORP and ORF (r(g) = 0.41 +/- 0.09 for both traits).
      Average genetic trends in OR and PS lines were, respectively, 0.49 +/- 0.10 and
      0.11 +/- 0.10 for ORP, and 0.43 +/- 0.11 and 0.11 +/- 0.11 for ORF. Responses to
      selection were slightly superior in the left than in the right ovary. No
      significant difference was found for PS or CPS in any of the lines. The TNB did
      not change in the OR line but significantly improved in the PS line (0.24 +/-
      0.11 piglets/generation).

PMID- 17235021
TI  - Evaluation of reciprocal differences in Bos indicus x Bos taurus backcross calves
      produced through embryo transfer: I. Birth and weaning traits.
AB  - Angus (A) and Bos indicus (B; Brahman or Nellore) reciprocal backcross, embryo
      transfer calves, belonging to 28 full-sib families, were evaluated for
      differences in birth weight, gestation length, and weaning weight. Two methods
      were investigated; method I made no distinction between how the F(1) parents were
      produced, whereas method II distinguished between the 2 types of F(1) parents (AB
      vs. BA corresponding to A x B vs. B x A, respectively). Bos indicus backcross
      calves had a 4.3 d longer (P < 0.05) gestation length but did not differ in their
      average birth weight from A backcrosses. Among B backcrosses, B x F(1) calves had
      a 5.2 d longer (P = 0.01) gestation length than F(1) x B calves (290.5 vs. 285.3,
      respectively). Under method II analysis, there was a consistent trend for
      gestation length, in which BA F(1) parents produced calves that ranked greater
      than calves from AB F(1) parents, as sires and dams. Crosses with a greater
      proportion of B in the sire in relation to the amount in the dam had a heavier (P
      < 0.05) birth weight (F(1) x A and B x F(1); 38.1 and 38.4 kg, respectively) than
      their respective reciprocal crosses (A x F(1) and F(1) x B; 34.3 and 33.5 kg,
      respectively). The F(1) x A and B x F(1) crosses showed a large difference in
      birth weight between males and females (5.3 and 4.1 kg, respectively), whereas A
      x F(1) and F(1) x B crosses showed a small difference (P > 0.10) in birth weight
      between males and females (1.5 and 1.1 kg, respectively). Further examination
      within each sex showed a difference between male reciprocals that was generally
      much larger than that between female reciprocals. Calves with a greater
      percentage of B in the sire compared with the proportion in the dam ranked
      heavier for weaning weight as for birth weight, though these differences were not
      significant. In breeding systems involving B x Bos taurus crosses, even when
      using embryo transfer, not only does the breed composition of the calves affect
      their preweaning performance, but the particular cross that produces the calves
      also should be considered in making breeding decisions.

PMID- 17235022
TI  - Evaluation of reciprocal differences in Bos indicus x Bos taurus backcross calves
      produced through embryo transfer: II. Postweaning, carcass, and meat traits.
AB  - Angus (A) x Bos indicus (B; Brahman or Nellore) reciprocal backcross, embryo
      transfer calves belonging to 28 full-sib families were evaluated for differences
      in feedyard initial BW, feedyard final BW, carcass weight, LM area, adjusted fat
      thickness, intramuscular fat, and Warner-Bratzler shear force. Two methods of
      analysis were investigated; method I made no distinction between how the F(1)
      parents were produced, whereas method II distinguished the 2 types of F(1)
      parents (AB vs. BA, corresponding to A x B vs. B x A, respectively). No
      significant reciprocal differences for these weight and carcass traits were
      detected under method I analyses, although the same trend existed for subsequent
      BW rankings as for birth weight and weaning weight. For each weight phase, the
      cross that involved a larger proportion of B in the sire in relation to the
      amount in the dam (F(1) x A and B x F(1)) ranked heavier than the respective
      reciprocal cross (A x F(1) and F(1) x B). As a whole, A backcross calves had
      larger (P < 0.001) LM area, more (P < 0.001) marbling, and lower (P < 0.001)
      Warner-Bratzler shear force than B back-cross calves, but no consistent trends
      were detected between reciprocal crosses for any of these traits, in contrast
      with the trends observed for the weight traits. Furthermore, males were heavier
      than females entering (P < 0.001) and leaving (P < 0.001) the feedyard, produced
      a heavier carcass (P < 0.001), and had larger LM area (P < 0.05) with less
      adjusted fat (P < 0.001). No difference existed between the sexes for Warner
      Bratzler shear force or marbling. No interactions involving sex, sire type, and
      dam type were observed for any of these traits. The results were similar under
      methods I and II analyses, with the exception that a significant sire type x dam
      type interaction was observed for initial feedyard BW. Results from this study
      suggest that for weight-related traits, both the breed constitution of the embryo
      transfer calf and the cross that produces the calf play an important role in its
      ultimate performance for B crossbred calves. For body composition and meat
      related traits, it appears that the breed makeup of the embryo transfer calf
      itself is more important to animal performance than the specific cross used to
      produce the calf.

PMID- 17235023
TI  - Lipogenesis and stearoyl-CoA desaturase gene expression and enzyme activity in
      adipose tissue of short- and long-fed Angus and Wagyu steers fed corn- or hay
      based diets.
AB  - Angus and Wagyu steers consuming high-roughage diets exhibit large differences in
      adipose tissue fatty acid composition, but there are no differences in terminal
      measures of stearoyl-CoA desaturase (SCD) activity or gene expression. Also,
      adipose tissue lipids of cattle fed corn-based diets have greater MUFA:SFA ratios
      than cattle fed hay-based diets. We hypothesized that any changes in SCD gene
      expression and activity would precede similar changes in adipose tissue
      lipogenesis between short- and long-fed endpoints. Furthermore, changes in SCD
      activity and gene expression between production endpoints would differ between
      corn- and hay-fed steers and between Wagyu and Angus steers. Angus (n = 8) and
      Wagyu (n = 8) steers were fed a corn-based diet for 8 mo (short-fed; 16 mo of
      age) or 16 mo (long-fed; 24 mo of age), whereas another group of Angus (n = 8)
      and Wagyu (n = 8) steers was fed a hay-based diet for 12 mo (short-fed; 20 mo of
      age) or 20 mo (long-fed; 28 mo of age) to match the end point BW of the corn-fed
      steers. Acetate incorporation into lipids in vitro was greater (P < 0.01) in corn
      fed steers than in hay-fed steers and tended (P = 0.06) to be greater in Wagyu
      than in Angus s.c. adipose tissue because the rate in Wagyu was twice that of
      Angus adipose tissue in the corn-fed, short-fed steers. There were diet x end
      point interactions for lipogenesis in i.m. and s.c. adipose tissues (both P <
      0.01) because lipogenesis was 60 to 90% lower in the long-fed cattle than in
      short-fed cattle fed the corn-based diet. The greatest SCD enzyme activity in
      Angus s.c. adipose tissue was observed at 24 mo of age (corn-based diet), but
      activity in Wagyu adipose tissue was greatest at 28 mo of age (hay-based diet;
      breed x diet x end point interaction, P = 0.08). For short- vs. long-fed
      endpoints in Angus, s.c. adipose tissue SCD activity was less (hay diet) or the
      same (corn diet). Conversely, SCD gene expression was greatest in long-fed Wagyu
      steers fed the hay- or corn-based diets (breed x end point interaction; P <
      0.01). Contrary to our hypotheses, SCD activity increased over time, whereas
      lipogenesis from acetate decreased. However, the developmental pattern of SCD
      gene expression and activity differed markedly between hay-fed Angus and Wagyu
      adipose tissues, which may explain the differences in the MUFA:SFA ratios
      observed in adipose tissues from these cattle.

PMID- 17235024
TI  - Identification of differentially expressed transcripts in bovine rumen and
      abomasum using a differential display method.
AB  - The rumen has several important physiological functions: absorption, transport,
      metabolic activity, and protection. To clarify the molecular basis underlying the
      physiological function of the rumen, reticulum, omasum, and abomasum, we used
      mRNA differential display to isolate and identify differentially expressed genes
      in these tissues. We isolated 18 transcripts that coexpressed in the rumen,
      reticulum, and omasum. Five genes, ribosomal protein 19 (RPS19), basic helix-loop
      helix domain containing class B2 (BHLHB2), NADH dehydrogenase flavoprotein 2
      (NDUFV2), exosome component 9 (EXOSC9), and ribosomal protein 23 (RPS23), were
      highly expressed in the rumen of adult Holstein and Japanese Black cattle.
      Significant differences of expression were observed in the abomasum compared with
      the rumen, reticulum, and omasum. To investigate the expression pattern of these
      genes during the neonatal growth stage, the relative levels of gene expression
      were analyzed in the rumen and abomasum of 3-wk-, 13-wk-, and 18- to 20-mo-old
      Holstein cattle. The expression level of RPS19 did not change with age in the
      rumen and abomasum. The levels of BHLHB2, NDUFV2, and EXOSC9 mRNA in the abomasum
      decreased (P < 0.05) after weaning and declined (P < 0.05) further in adults; in
      contrast, expression in the rumen was not altered. Interestingly, the levels of
      RPS23 mRNA in the rumen increased (P < 0.05) after weaning and further increased
      in the adult; however, the level of expression of this gene decreased (P < 0.05)
      in the abomasum with weaning and age. This indicates that the 4 tissues,
      especially the rumen and abomasum, have different developmental pathways after
      birth and subsequent onset of rumination.

PMID- 17235025
TI  - Exocrine pancreatic secretion in pigs fed sow's milk and milk replacer, and its
      relationship to growth performance.
AB  - The objective of this study was to quantify and compare the effects of sow's milk
      and 2 milk replacer diets (containing clotting or non-clotting protein sources)
      on exocrine pancreatic secretion, plasma cholecystokinin, and immunoreactive
      cationic trypsin in pigs. In addition, the relationship between exocrine
      pancreatic secretion and growth in milk-fed pigs was studied. In a changeover
      experiment, 9 chronically catheterized pigs of 6.6 +/- 0.19 kg of BW were studied
      for 3 wk. Pigs were assigned to each of 3 diets. Exocrine pancreatic secretion
      was measured from the third to the seventh day on each diet. The protein content
      and trypsin activity of the pancreatic juice were measured. Blood samples were
      taken at 10 min before and after milk ingestion and were analyzed for
      cholecystokinin and immunoreactive cationic trypsin. Pancreatic protein and
      trypsin secretion did not differ between pigs fed sow's milk and those fed milk
      replacer, but the volume secreted was less for the pigs fed sow's milk (0.75 vs.
      1.03 mL x kg(-1) x h(-1); P < 0.01). A postprandial response to milk intake was
      not observed. The 2 milk replacer diets did not affect exocrine pancreatic
      secretion differently. The average exocrine pancreatic secretion (volume, 0.94 mL
      x kg(-1) x h(-1); protein, 4.28 mg x kg(-1) x h(-1); trypsin, 1.65 U x kg(-1) x
      h(-1)) was intermediate between literature values for suckling and weaned pigs.
      Plasma cholecystokinin was elevated (approximately 18 pmol x L(-1)) and showed
      low correlations with the pancreatic secretion traits. Plasma immunoreactive
      cationic trypsin was not significantly related to any of the pancreatic secretion
      traits and should therefore not be used as an indicator for exocrine pancreatic
      function in milk-fed pigs. Exocrine pancreatic secretion varied substantially
      among individual pigs (protein, 0.22 to 13.98 mg x kg(-1) x h(-1)). Pancreatic
      protein and trypsin secretion showed a positive, nonlinear relationship with
      performance traits. It was concluded that neither specific sow's milk ingredients
      nor the protein source are responsible for a low pancreatic protein secretion in
      suckling pigs. Exocrine pancreatic secretion was positively correlated with ADG
      in pigs at an identical milk intake.

PMID- 17235026
TI  - Response to ractopamine-hydrogen chloride is similar in yearling steers across
      days on feed.
AB  - Yearling steers (n = 2,552; 314 kg of initial BW) were used to evaluate the
      effects of ractopamine-HCl (RAC) and days on feed on performance, carcass
      characteristics, and skeletal muscle gene expression in finishing steers.
      Treatment groups included serial slaughter dates of 150, 171, or 192 d on feed.
      Within each slaughter date, steers either received RAC (200 mg/steer) daily for
      the final 28 d or were not fed RAC. All steers were initially implanted with
      Revalor-IS and were reimplanted with Revalor-S after 75 d on feed. At slaughter,
      muscle samples from the semimembranosus were collected for mRNA analysis of the
      beta-adrenergic receptors (beta-AR). Ractopamine administration increased (P <
      0.05) ADG, G:F, and HCW and increased (P = 0.08) LM area. Ractopamine did not
      affect the dressing percentage, USDA yield grade, or quality grade (P > 0.3).
      There was no change in overall feed intake across the entire feeding period;
      however, feed intake was increased during the 28-d period during which the steers
      were fed RAC (P < or = 0.05). Greater days on feed decreased (P < 0.05) ADG, G:F,
      DMI, and the number of yield grade 1 and 2 carcasses. Also, greater days on feed
      increased (P < 0.05) HCW, dressing percentage, and the number of prime and choice
      carcasses, as well as the number of yield grade 4 and 5 carcasses. Increasing
      days on feed decreased (P < 0.05) the abundance of beta(1)-AR and beta(3)-AR mRNA
      and increased (P < 0.05) the abundance of beta(2)-AR mRNA in skeletal muscle
      samples obtained at slaughter. Ractopamine had no effect (P > 0.10) on the
      abundance of beta(1)-AR or beta(3)-AR mRNA, but tended (P = 0.09) to increase
      beta(2)-AR mRNA. Additional time-course studies with primary muscle cell cultures
      revealed that advancing time in culture increased (P < 0.001) beta(2)-AR mRNA but
      had no effect (P > 0.10) on beta(1)-AR or beta(3)-AR mRNA. We conclude that days
      on feed and RAC are affecting beta-AR mRNA levels, which could, in turn, impact
      the biological response to RAC feeding in yearling steers.

PMID- 17235027
TI  - Social rank of pregnant sows affects their body weight gain and behavior and
      performance of the offspring.
AB  - Previous studies on group housing of pregnant sows have mainly focused on
      reproduction, but we hypothesized that the social rank of pregnant sows housed in
      groups could also affect birth weight, growth, and behavior of their offspring.
      Therefore, in the present study, pregnant gilts and sows were housed in 15
      different groups (n = 7 to 14 animals per group) from 4 d after AI until 1 wk
      before the expected farrowing date. All groups were fed by an electronically
      controlled sow feeding system that registered, on a 24-h basis, the time of first
      visit, number of feeding and non-feeding visits, and number of times succeeding
      another sow within 2 s. Only in the first 6 groups (n = 57 animals), agonistic
      interactions were observed continuously. The percentage of agonistic interactions
      won was highly correlated (r(s) = 0.90, P < 0.001) with the percentage of
      displacement success (DS) at the feeding station, which was calculated as: [the
      number of times succeeding another sow within 2 s/(the number of times succeeded
      by another sow within 2 s + the number of times succeeding another sow within 2
      s)] x 100. This allowed us to classify all sows (n = 166) according to their DS:
      high-social ranking (HSR) sows had a DS >50% (n = 62) and low-social ranking
      (LSR) sows a DS <50% (n = 104). Body weights before AI did not differ between HSR
      and LSR sows, but HSR sows gained more BW during gestation, and lost more BW and
      back-fat during lactation (P < 0.001). Maternal salivary cortisol concentrations
      at 2, 7, and 13 wk after AI did not differ between HSR and LSR sows, nor did
      gestation length, litter size, or percentage of live born piglets. During a novel
      object (NO) test at 3 wk of age, HSR offspring moved and vocalized more than LSR
      offspring (P < 0.05). In addition, the latency time to touch the NO was shorter
      in HSR offspring (P < 0.05), and HSR males spent more time near the NO than LSR
      males (P < 0.01). At weaning, HSR offspring weighed more than LSR offspring (P <
      0.05), and at slaughter HSR offspring had more lean meat than LSR offspring (P <
      0.05). Results indicate that the social rank of the sow during gestation affects
      her own BW gain and loss as well as the growth and behavior of her offspring. Pig
      breeders that apply group housing for pregnant sows should pay attention to
      reducing competition around the feeding area, which may reduce aggression among
      the sows and minimize differences between HSR and LSR sows.

PMID- 17235028
TI  - The effect of anabolic implants on intramuscular lipid deposition in finished
      beef cattle.
AB  - Two experiments were conducted to determine the effects of anabolic implants on
      performance, changes in ultrasound measurements, carcass quality, cellularity of
      i.m. and s.c. adipose depots, and mRNA expression of acetyl CoA carboxylase
      (ACC), stearoyl CoA desaturase (SCD), and lipoprotein lipase (LPL) in i.m.
      adipose tissue of finished beef cattle. Angus heifers (experiment 1: n = 10; 411
      kg of BW) and steers (experiment 2: n = 18; 279 kg of BW) were randomly allotted
      as control (C) or implanted with Synovex-Plus (SP) at d 0 and midway through the
      finishing period. The cattle were fed a high-concentrate diet and were weighed at
      approximately 28-d intervals. Heifers and steers were finished for 108 and 133 d,
      respectively. At slaughter, a section of the LM (sixth to ninth rib) was removed,
      and i.m. adipose tissue was dissected for mRNA analysis. Subcutaneous and i.m.
      adipose tissues also were collected for determination of cellularity. At 48 h
      postmortem, carcass data were collected, and a steak (12th rib) was removed for
      analysis of lipid and fatty acid composition. Body weight did not differ (P >
      0.10) between treatments until after reimplanting of the heifers (d 55) or steers
      (d 73). Average daily gain was 36 and 16% faster (P < or = 0.01) for implanted
      heifers and steers, respectively, compared with their control counterparts.
      Implanting resulted in larger (P < or = 0.10) HCW and LM area for heifers and
      steers. However, implanting did not affect (P > 0.10) dressing percent, fat
      thickness, percentage of KPH, yield grade, or marbling score. Intramuscular lipid
      content and concentrations of major fatty acids did not differ (P > 0.10) between
      treatments. Percentage of SC adipocytes was greater at larger diameters ( > 150
      microm), whereas the majority of i.m. adipocytes were at small to middle
      diameters (50 to 150 microm). The number of i.m. adipocytes per gram of tissue
      was greater (P < 0.05) for SP than C and also were greater (P < 0.05) than the
      number of s.c. adipocytes in SP heifers. In experiment 2, adipocytes per gram of
      tissue tended to be greater (P = 0.07) for SP than C and were greater (P < 0.01)
      for i.m. than s.c. In experiment 1, average cell diameter and volume did not
      differ (P > 0.10) between treatments and tissues, but in experiment 2 both
      cellularity traits were greater (P < 0.01) for s.c. than for i.m.. Implanting did
      not alter mRNA expression of ACC, SCD, or LPL in i.m. adipose tissue. This study
      shows that anabolic implants do not appear to have direct effects on i.m. lipid
      deposition.

PMID- 17235029
TI  - Assessing the adaptation of swine to fifty-seven hours of feed deprivation in
      terms of behavioral and physiological responses.
AB  - Dramatic changes in the livestock industry have brought about widespread concern
      regarding the welfare of animals in terms of the hunger that they may experience.
      Despite this concern, animal science has not been able to provide a methodology
      that can objectively determine whether the welfare of animals is compromised by
      hunger. The current work sought to provide data that characterized the
      physiological and behavioral responses of animals experiencing 57 h of food
      deprivation. For this purpose, 2 separate experiments were conducted, in which
      physiological or behavioral measures were collected from swine deprived of feed
      for 21 to 57 h or fed normally (physiology, n = 20/treatment; behavior, n =
      8/treatment). Treatment x time interactions were found (P < 0.02) for insulin,
      beta-hydroxybutyrate, NEFA, drinking, standing, inactivity, lying sternal, lying
      lateral, and total lying. Animals appeared to adjust appropriately to the
      metabolic challenge imposed, as suggested by increases in alternative energy
      substrates (NEFA, beta-hydroxybutyrate). Additionally, feed-deprived animals
      appeared less active than control animals until after 45 h of feed deprivation,
      when the former appeared to be more active. Our results suggest that feed
      deprivation of finishing pigs for durations greater than 45 h produced behavioral
      changes that may be related to increased sensations of hunger and which possibly
      are dependent on the use of alternative energetic substrates. Our data link
      behavioral and physiological changes after the imposition of feed deprivation.

PMID- 17235030
TI  - Technical note: detection of chicken, turkey, duck, and goose tissues in
      feedstuffs using species-specific polymerase chain reaction.
AB  - PCR method was applied for the qualitative identification of chicken (Gallus
      gallus), turkey (Meleagris gallipavo), duck (Anas platyrhynchos x Cairina
      muschata), and goose (Anser anser) tissues in feed-stuffs, on an individual
      basis. The assay uses oligonucleotide primers that are specific for each avian
      species, targeting the 12S rRNA mitochondrial gene. The primers designed
      generated amplicons of 95, 122, 64, and 98 bp length for chicken, turkey, duck,
      and goose, respectively. The specificity of the primers was tested against 29
      animal species including mammals, birds, and fish, as well as 8 plant species.
      Analysis of experimental feedstuffs demonstrated the detection of each target
      species in the range of 0.1 to 100%. The performance of this method was not
      affected by prolonged heat-treatment (up to 133 degrees C for 20 min at 300 kPa),
      and consequently, it could be very useful for the accurate identification of
      tissues from these 4 avian species in products submitted to denaturing
      technologies, for which other methods cannot be applied.

PMID- 17235031
TI  - Effects of Acid LAC and Kem-Gest acid blends on growth performance and microbial
      shedding in weanling pigs.
AB  - Weanling pigs with mean initial BW of 6.04 kg (Exp.1) and 5.65 kg (Exp. 2) and
      mean age at weaning of 18.2 d (Exp. 1) and 17.7 d (Exp. 2) were used in two 5-wk
      experiments (Exp. 1, n = 180; Exp. 2, n = 300) to evaluate the effects of an
      organic acid blend (Acid LAC, Kemin Americas Inc., Des Moines, IA) and an
      inorganic/organic acid blend (Kem-Gest, Kemin Americas Inc.) on weanling pig
      growth performance and microbial shedding. In Exp. 1, the 5 dietary treatments
      were 1) negative control, 2) diet 1 + 55 ppm carbadox, 3) diet 1 + 0.4% Acid LAC,
      4) diet 1 + 0.2% Kem-Gest, 5) diet 1 + 0.4% Acid LAC and 0.2% Kem-Gest. In Exp.
      2, the 6 dietary treatments were diets 1 through 4 corresponding to Exp. 1, plus
      5) sequence 1: 0.4% Acid LAC for 7 d followed by 0.2% Kem-Gest for 28 d, and 6)
      sequence 2: 0.2% Kem-Gest for 7 d followed by 0.4% Acid LAC for 28 d. Pigs were
      housed at 6 (Exp. 1) or 10 (Exp. 2) pigs/pen. Treatments were fed throughout the
      experiment in 3 phases: d 0 to 7, d 7 to 21, and d 21 to 35. In Exp. 1, there
      were no differences (P > 0.05) in ADG, ADFI, or G:F among the dietary treatments
      at any time during the study. In Exp. 2, throughout the study, pigs fed carbadox
      (diet 2) and sequence 1 (diet 5) diets had the greatest ADG (d 0 to 35; 262, 294,
      257, 257, 292, and 261 g/d, diets 1 through 6, respectively; P < 0.05), greater
      ADFI than all other acid treatments (P < 0.05), and tended to have greater ADFI
      than diet 1 (P < 0.10). Fecal pH, Escherichia coli concentrations, and Salmonella
      presence were determined at d 6, 20, and 34 for Exp. 1, and on d 32 for Exp. 2.
      For both experiments, there was no effect of treatment on the presence of fecal
      Salmonella (P > 0.10) at any sampling time. In Exp. 1, fecal E. coli
      concentrations for pigs fed the carbadox (P < 0.05) diet were greater than for
      pigs fed the combination diet with 0.4% Acid LAC and 0.2% Kem-Gest on d 34, and
      the pigs fed the negative control diet tended (P < 0.10) to have greater fecal E.
      coli concentrations than those fed the combination diet on d 34. In Exp. 2, fecal
      pH of pigs fed sequence 1 tended to be greater than fecal pH of pigs fed diet 1,
      diet 4, or sequence 2 (P < 0.10), but there was no dietary effect on fecal E.
      coli. In Exp. 1, growth performance of pigs fed the Acid LAC and Kem-Gest diets
      was similar to each other and to that of the carbadox-fed pigs. Adding the
      combination of 0.4% Acid LAC and 0.2% Kem-Gest to nursery pig diets reduced ADFI
      and pig growth rate. In Exp. 2, pigs fed the acid sequence of Acid LAC-Kem-Gest
      had similar growth performance to pigs fed carbadox, and this novel dietary acid
      sequence may have merit as a replacement for antibiotics in the nursery phase.

PMID- 17235033
TI  - Comparison of visual and electronic identification devices in pigs:
      slaughterhouse performance.
AB  - Traceability during slaughter was studied in 1,581 pigs identified by different
      devices. Treatments were visual ear tags (n = 1,300), electronic ear tags of
      different technologies (half-duplex, n = 636; full-duplex, n = 632), and
      intraperitoneally injected transponders of different technologies (half-duplex 32
      mm, n = 645; full-duplex 34 mm, n = 642). Piglets were individually identified at
      weaning and intensively fed until 100 kg of BW. Pigs were slaughtered in 2
      commercial slaughterhouses (including scalding, flaming, and peeling) at
      different throughputs (450 and 550 pigs/h). Readability during slaughtering was
      checked visually and using standardized hand-held transceivers. No effect of
      slaughterhouse was detected (P > 0.05). Ear tag losses in the slaughtering line
      were similar for visual (3.7%) and half-duplex (3.5%) but were increased for full
      duplex (11.5%; P < 0.05). Moreover, electronic failures during slaughtering did
      not differ (P > 0.05) between ear tags (half-duplex, 1.1%; full-duplex, 0.6%).
      Intraperitoneally injected transponders were not affected by slaughtering
      (retention 100%, no failures), and 89.0% of the transponders were manually
      recovered from the abdominal viscera in the offal trays. The remaining
      transponders (11.0%) were lost on the floor, but none were found in the
      carcasses. No differences (P > 0.05) in recovery were observed between
      intraperitoneal transponders. Considering on-farm and slaughterhouse data, total
      traceability from farm to carcass release was greater (P < 0.05) for
      intraperitoneally injected transponders (98.2%) than for ear tags. Between ear
      tags, the greatest traceability was obtained with visual tags (95.7%), which
      differed (P < 0.05) from electronic tags (half-duplex, 91.4%; full-duplex, 84.5%;
      P < 0.05). Intraperitoneally injected transponders were an efficient and reliable
      identification system for tracing pigs from farm to the end of the slaughter
      line, allowing the transfer of pig identification to the carcass. Adherence of
      intraperitoneally injected transponders to the viscera should be improved to
      reduce risks of loss in the meat chain. A dual system based on intraperitoneally
      injected transponders and plastic ear tags would allow a redundant and automatic
      reading system that is efficient and reliable for data management and
      traceability in the swine industry.

PMID- 17235032
TI  - Effects of continuous versus intermittent transport on plasma constituents and
      antibody response of lambs.
AB  - Recommendations for transportation of lambs, horses, calves, and pigs from a
      committee of the European Commission, which required rest stops of 6 or 24 h,
      every 8 h, were evaluated using Rambouillet x Suffolk lambs. The lambs of 17.6 +/
      0.5 kg of BW were randomly assigned to 1 of 3 treatments: transported for 22 h
      (continuous; n = 15); transported for 8 h, unloaded and rested for 6 h,
      transported for 8 h, unloaded and rested for 24 h, transported for 6 h (rested, n
      = 15); or remained in the home pasture throughout the study (control, n = 16).
      Off-trailer rest with food and water occurred in novel pens. Food deprivation in
      the continuous lambs was reflected by a decrease (P < 0.001) in plasma
      concentrations of glucose and an increase (P < 0.02) in plasma concentrations of
      blood urea nitrogen, creatinine, and total bilirubin relative to rested or
      control lambs. Electrolytes varied within and among all 3 treatments (P < 0.05),
      but no distinct pattern indicating dehydration was evident. Serum concentrations
      of cortisol were elevated in continuous and rested lambs compared with control
      lambs at 22 h (P < 0.05). Plasma immunoglobulin G antibody response to ovalbumin
      was suppressed (P < 0.05) in the continuous and rested lambs relative to the
      control lambs. Differences (P < 0.05) between continuous and rested lambs
      indicated the rest stops were sufficient to maintain BW during transport;
      however, these results were confounded by the control lambs losing a similar (P =
      0.50) percentage of their initial BW as the continuous lambs at 22 h. The rest
      stops eliminated the physiological indicators of food deprivation and maintained
      BW but did not alleviate evidence of immunosuppression, and 52 h was required to
      complete the otherwise 22-h-long trip.

PMID- 17235034
TI  - Survival analysis from birth to slaughter of Ripollesa lambs under semi-intensive
      management.
AB  - The survivability from birth to slaughter of 1,487 Ripollesa lambs with a
      preslaughter overall mortality of 9.6% was studied under the proportional hazards
      framework, assuming a Weibull distribution for the baseline hazards function. A
      sire frailty model was fitted, with the common environment received by the lamb
      as an additional random source of variation. Common environment was considered
      time-dependent and was characterized by the dam and the contemporary lamb group
      during the preweaning and fattening periods, respectively. Only 3 fixed effects
      were statistically significant: the linear and quadratic effects of birth weight
      (P < 0.001), the relative position of the delivery within the lambing season (P <
      0.001), and the presence of stillbirths or mummified fetuses within the litter (P
      < 0.05). Birth type and parity of the ewe were significant only when birth weight
      was removed from the model (P < 0.001 and P < 0.05, respectively). Nevertheless,
      the model including birth weight became preferable according to the Akaike's
      information criterion. Survivability dramatically decreased with extreme birth
      weights, although it reached a survival probability greater than 93.5% within the
      3.3 to 5.4 kg range, indicating an optimum birth weight range of Ripollesa lambs
      for survival purposes. The hazard ratio (HR) increased for births occurring
      within the last third of the lambing period (HR = 1.70; P < 0.05), as well as for
      primiparous ewes that lambed in December and January (HR = 5.36; P < 0.001).
      Survival probability decreased for lambs born from litters with 1 or more
      stillbirths or mummified fetuses (HR = 1.61; P < 0.05). The variance component
      estimated for sire variance (0.07) was clearly lower than that of the common
      environment (1.87), with a heritability estimate of 0.027.

PMID- 17235035
TI  - Effects of breed, sex, and age on the variation and ability of fecal near
      infrared reflectance spectra to predict the composition of goat diets.
AB  - The effects of breed, sex, and age of goats on fecal near-infrared reflectance
      spectroscopy-predicted percentage juniper in the diet were investigated, as were
      spectral differences in feces from goats differing in estimated genetic merit for
      juniper consumption. Eleven goats from each breed, sex, and age combination,
      representing 2 breeds (Angora and meat-type), 3 sex classifications (female,
      intact male, and castrated male), and 2 age categories [adult and kid (less than
      12 mo of age)] were fed complete, pelleted rations containing 0 or 14% juniper.
      After 7 d on the same diet, fecal samples were collected for 3 d, and the spectra
      from the 3 replicate samples were averaged. Fecal samples were assigned to
      calibration or validation data sets. In a second experiment, Angora and meat
      goats with high or low estimated genetic merit for juniper consumption were fed
      the same diet to determine the effect of consumer group on fecal spectra. Feces
      were scanned in the 1,100- to 2,500-nm range with a scanning reflectance
      monochromator. Fecal spectra were analyzed for the difference in spectral
      characteristics and for differences in predicted juniper in the diet using
      internal and independent calibration equations. Internal calibration had a high
      precision (R(2) = 0.94), but the precision of independent validations (r(2) =
      0.56) was low. Spectral differences were affected by diet, sex, breed, and age (P
      < 0.04). However, diet was the largest source of variation in spectral
      differences. Predicted percentage of juniper in the diet also showed that diet
      was the largest source of variation, accounting for 95% of the variation in
      predictions from internal calibrations and 51% of the variation in independent
      validations. Predictions from independent calibrations readily detected
      differences (P < 0.001) in the percentage of juniper in the 2 diets, and the
      predicted differences were similar to the actual differences. Predicted juniper
      in the diet was also affected by sex. Feces from goats from different juniper
      consumer groups fed a common diet were spectrally different, and the difference
      may have resulted from a greater intake by high- compared with low-juniper
      consuming goats. Fecal near-infrared reflectance spectroscopy predictions of
      botanical composition of diets should be considered an interval scale of
      measurement.

PMID- 17235036
TI  - Effect of species of cool-season annual grass interseeded into Bermudagrass sod
      on the performance of growing calves.
AB  - Two experiments were conducted to evaluate the effect of species of cool-season
      annual grass on the growth of stocker cattle over 3 yr. In Exp. 1, the small
      grains (SG) oat (O), rye (R), and wheat (W), or combinations of SG and annual
      ryegrass (RG), were interseeded into Bermudagrass sod in a completely randomized
      design with a 3 x 2 factorial arrangement of treatments. In Exp. 2, RG was
      planted alone or with O, R, triticale (T), or W in a completely randomized
      design. Pastures were planted in late October of each year, and seeding rates
      were 134.4 and 22.4 kg/ha for SG and RG, respectively. In Exp. 1, grazing was
      initiated on December 18. In Exp. 2, grazing was initiated on December 23 for SG
      pastures and January 21 or February 16 for RG pastures in yr 1 and on December 8
      for all pastures in yr 2. Grazing was managed using the put-and-take method, in
      which additional calves were added as needed to maintain equal grazing pressure
      among pastures. In Exp. 1, no interactions (P > or = 0.28) were detected, so the
      main effects of SG species and RG addition are discussed. From December 18 to
      March 12, there were no differences in ADG (P > or = 0.17), whereas during the
      spring (from March 12 to May 7), addition of RG increased (P = 0.05) ADG. Using
      RG increased (P < or = 0.01) animal grazing-days/hectare and BW gain/hectare.
      Wheat tended (P = 0.08) to increase BW gain/hectare compared with the other SG,
      and O tended (P = 0.09) to produce less BW gain/hectare than the other SG. The
      treatment x year interaction was significant (P < or = 0.05) in Exp. 2. In yr 1,
      no differences (P = 0.25) were observed for ADG from December 23 to March 8, but
      during the spring grazing period (from March 8 to May 5), ADG of calves grazing
      TRG was less (P < or = 0.04) than that of those grazing RG, RRG, or WRG. The RRG
      combination produced more (P < or = 0.03) BW gain/hectare than ORG, RG, or TRG
      and tended (P = 0.06) to produce more BW gain/hectare than WRG. The WRG
      combination produced more (P < or = 0.05) BW gain/hectare than TRG and RG, and
      ORG tended (P = 0.09) to produce more BW gain/hectare than RG alone. Pastures
      planted to R or W produced more (P < or = 0.05) BW gain/hectare than RG alone or
      T. During yr 2, there were no differences (P > or = 0.44) in ADG, BW
      gain/hectare, or grazing-days/hectare. In conclusion, the choice of cool-season
      annual to establish is highly weather-dependent, but R and W are generally
      superior to other small grains, and RG is a necessary complement to SG when
      interseeding cool-season annuals into Bermudagrass sod.

PMID- 17235037
TI  - Chemical composition and in situ dry matter and fiber disappearance of sorghum x
      Sudangrass hybrids.
AB  - Three sorghum x Sudangrass hybrids were planted in twelve 0.2-ha plots to test
      the effect of date of harvest and hybrid on plant maturity, DM yield, chemical
      composition, and in situ DM and fiber disappearance. Sweet Sunny Sue (a non-brown
      midrib (BMR) hybrid; nonBMR), NutriPlus BMR (a BMR hybrid; NP-BMR), and Dry Stalk
      BMR (a BMR hybrid; DS-BMR) were planted on 26 June 2003 at 22.4 kg of seed/ha.
      Beginning 34 d after planting, plant height and phenological growth stage were
      assessed weekly in 10 random, 0.5-m(2) quadrats per plot. Plants were clipped to
      2.5 cm in height and analyzed for CP, NDF, and ADF using near-infrared
      spectroscopy. Composite samples harvested from each plot on d 34, 48, and 63 were
      incubated in the rumen of 3 steers to determine the in situ disappearance of DM
      and NDF in a 3 x 3 Latin square. Forage yield was greater (P < or =0.02) for
      nonBMR than NP-BMR on d 41 and 55 and tended (P = 0.08) to be greater on d 48.
      The DS-BMR hybrid produced more (P = 0.04) forage DM than the NP-BMR on d 48.
      When DM yield was regressed on growth stage at harvest, BMR hybrids were
      predicted to produce 265 kg/ha more DM (P < 0.01) than nonBMR, at the late-boot
      stage. At all harvest dates, NDF concentrations were less (P < or =0.02) for BMR
      than nonBMR. The DS-BMR had greater (P < or =0.02) NDF concentrations than NP-BMR
      on d 41, 48, 55, and 63. Detergent fiber concentrations were predicted to be
      greater (P < 0.01) in nonBMR than BMR when regressed on growth stage at harvest,
      but the magnitude of the differences in fiber concentration diminished with
      growth stage. The A fractions of DM and NDF were greater (P < 0.01) and the C
      fraction was less (P < 0.01) for BMR hybrids than nonBMR. The B fraction of DM
      was not affected (P = 0.15) by hybrid type. The B fraction of NDF was not
      different (P = 0.28) on d 34 but was greater (P < 0.01) on d 48 and 63 for BMR
      than nonBMR. Effective degradability of NDF and DM was greater (P < 0.02) for BMR
      than nonBMR on all harvest dates. The A fraction of DM was less for DS-BMR than
      NP-BMR (P < 0.01), but the B and C fractions of NDF and DM did not differ (P >
      0.13) between BMR hybrids. This research indicates that forage chemical
      composition and ruminal in situ disappearance are improved in the BMR sorghum x
      Sudangrass hybrids tested compared with the nonBMR. Yield reductions are commonly
      reported for BMR hybrids, but predicted DM yields in the current study were not
      reduced if harvested at a similar phenological growth stage.

PMID- 17235038
TI  - Board-invited review: the ethical and behavioral bases for farm animal welfare
      legislation.
AB  - Concerns about farm animal welfare vary among individuals and societies. As
      people increasingly consider the values underlying current farm animal production
      methods, farm animal welfare policy debates have escalated. Recent food animal
      protection policies enacted in the European Union have fueled highly contentious
      discussions about the need for similar legislative activity in the United States.
      Policymakers and scientists in the United States are apprehensive about the
      scientific assessment, validation, and monitoring of animal welfare, as well as
      the unforeseen consequences of moving too hastily toward legislating farm animal
      welfare. The potential impact of such legislation on producers, food prices,
      animals, and concerned citizens must also be considered. Balancing the interests
      of all stakeholders has therefore presented a considerable challenge that has
      stymied US policymaking. In this review, we examine the roles of ethics and
      science in policy decisions, discuss how scientific knowledge relative to animal
      behavior has been incorporated into animal welfare policy, and identify
      opportunities for additional refinement of animal welfare science that may
      facilitate ethical and policy decisions about animal care.

PMID- 17235039
TI  - Poor-prognosis germ cell tumors: we have not yet crossed the finish line.

PMID- 17235040
TI  - Targeting HER2 in prostate cancer: where to next?

PMID- 17235041
TI  - On referral patterns for patients with breast cancer.

PMID- 17235042
TI  - Phase III randomized trial of conventional-dose chemotherapy with or without high
      dose chemotherapy and autologous hematopoietic stem-cell rescue as first-line
      treatment for patients with poor-prognosis metastatic germ cell tumors.
AB  - PURPOSE: To investigate the role of high-dose chemotherapy (HDCT) as first-line
      treatment in patients with metastatic germ cell tumor (GCT) and poor-prognostic
      clinical features. Serum tumor marker decline during chemotherapy was assessed
      prospectively as a predictor of treatment outcome. PATIENTS AND METHODS: In this
      randomized phase III trial, previously untreated patients with intermediate- or
      poor-risk GCT received either four cycles of standard bleomycin, etoposide, and
      cisplatin (BEP alone), or two cycles of BEP followed by two cycles of HDCT
      containing carboplatin and then by hematopoietic stem-cell rescue (BEP + HDCT).
      Serum tumor markers alpha-fetoprotein and human chorionic gonadotrophin were
      correlated with treatment outcome as a secondary end point. RESULTS: Two hundred
      nineteen patients were randomly assigned: 108 to BEP + HDCT and 111 to BEP alone.
      The 1-year durable complete response rate was 52% after BEP + HDCT and 48% after
      BEP alone (P = .53). Patients with slow serum tumor marker decline (alpha
      fetoprotein and/or human chorionic gonadotrophin) during the first two cycles of
      chemotherapy had a shorter progression-free survival and overall survival
      compared with patients with satisfactory marker decline (P = .02 and P = .03,
      respectively). Among 67 patients with unsatisfactory marker decline, the 1-year
      durable complete response proportion was 61% for patients who received HDCT
      versus 34% for patients receiving BEP alone (P = .03). CONCLUSION: The routine
      inclusion of HDCT in first-line treatment for GCT patients with metastases and a
      poor predicted outcome to chemotherapy did not improve treatment outcome.
      Frequent serum marker determinations to estimate marker decline during the first
      two cycles of BEP chemotherapy provide a clinically useful estimate of outcome.

PMID- 17235043
TI  - Open-label phase II study evaluating the efficacy and safety of two doses of
      pertuzumab in castrate chemotherapy-naive patients with hormone-refractory
      prostate cancer.
AB  - PURPOSE: To determine the prostate-specific antigen (PSA) 50% decline rate within
      24 weeks of starting treatment with single-agent pertuzumab in castrate patients
      with hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: Two
      independent Simon's two-stage designs were used to evaluate two doses of
      pertuzumab administered intravenously once every 3 weeks. An interim analysis of
      the first 23 assessable patients in the first cohort treated at 420 mg (loading
      dose of 840 mg) allowed termination of additional enrollment if three patients
      had a 50% decline in PSA after all patients had completed at least three cycles
      of therapy or withdrew due to insufficient therapeutic response, death, or study
      related toxicity before completing three cycles. A second cohort of patients
      treated at 1,050 mg could be enrolled with the same design, and if more than
      three patients had a 50% decline in PSA, 27 more patients would be treated at
      1,050 mg. RESULTS: Sixty-eight castrate, chemotherapy-naive men with HRPC were
      enrolled. A total of 35 patients were treated at 420 mg; no PSA declines 50% were
      observed at the interim analysis and recruitment was stopped. A total of 33
      patients were then treated at 1,050 mg, and no PSA declines 50% were observed at
      the interim analysis. Pertuzumab was well tolerated. CONCLUSION: Pertuzumab has
      no clinically significant single-agent activity in castrate patients with HRPC at
      either of the tested dose levels. This may reflect the continued presence of
      significant levels of intraprostatic androgen driving androgen receptor
      signaling.

PMID- 17235044
TI  - Patterns and correlates of patient referral to surgeons for treatment of breast
      cancer.
AB  - PURPOSE: Characteristics of surgeons and their hospitals have been associated
      with cancer treatments and outcomes. However, little is known about factors that
      are associated with referral pathways. METHODS: We analyzed tumor registry and
      survey data from women with breast cancer diagnosed in 2002 and reported to the
      Detroit and Los Angeles Surveillance, Epidemiology, and End Results registries (n
      = 1,844; response rate, 77.4%) and their attending surgeons (n = 365; response
      rate 80.0%). RESULTS: About half of the patients (54.3%) reported that they were
      referred to the surgeon by another provider or health plan; 20.3% reported that
      they selected the surgeon; and 21.9% reported that they both were referred and
      were involved in selecting the surgeon. Patients who selected the surgeon based
      on reputation were more likely to have received treatment from a high-volume
      surgeon (adjusted odds ratio [OR], 2.2; 95% CI, 1.5 to 3.4) and more likely to
      have been treated in an American College of Surgeons-approved cancer program or a
      National Cancer Institute (NCI) -designated cancer center (adjusted OR, 2.0; 95%
      CI, 1.3 to 3.1; adjusted OR, 3.4; 95% CI, 1.9 to 6.2, respectively). Patients who
      were referred to the surgeon were less likely to be treated in an NCI-designated
      cancer center (adjusted OR, 0.5; 95% CI, 0.3 to 0.9). CONCLUSION: Women with
      breast cancer who actively participate in the surgeon selection process are more
      likely to be treated by more experienced surgeons and in hospitals with cancer
      programs. Patients should be aware that provider or health plan-based referral
      may not connect them with the most experienced surgeon or comprehensive practice
      setting in their community.

PMID- 17235045
TI  - Predictors of prophylactic bilateral salpingo-oophorectomy compared with
      gynecologic screening use in BRCA1/2 mutation carriers.
AB  - PURPOSE: Women with BRCA1/2 gene mutations who have completed their childbearing
      are strong candidates for risk-reducing prophylactic bilateral salpingo
      oophorectomy (PBSO). The aim of the current study was to identify baseline
      predictors of PBSO versus gynecologic screening (GS) in this group of high-risk
      women. PATIENTS AND METHODS: Baseline questionnaires were available from 160
      BRCA1/2 carriers who participated in a nationwide, longitudinal, observational
      study of the psychosocial consequences of prophylactic surgery versus periodic
      screening. Topics addressed by the questionnaire included generic quality of
      life, cancer-specific distress, risk perception, knowledge of ovarian cancer, and
      perceived pros and cons of surgery versus screening. PBSO use during the 12-month
      period after the first gynecologic consultation was determined on the basis of
      medical record data. RESULTS: During the 12-month follow-up period, 74% of women
      had undergone PBSO, and 26% opted for screening. Statistically significant
      multivariate predictors of PBSO included education, general health perceptions,
      perceived incurability of ovarian cancer, and perceived benefits of surgery.
      CONCLUSION: Women with lower educational levels, with poorer general health
      perceptions, who view ovarian cancer as an incurable disease, and who believe
      more strongly in the benefits of surgery are more likely to undergo PBSO.
      Clinicians should ensure that high-risk women are well informed about the low
      predictive value of GS techniques and about the lethal threat posed by ovarian
      cancer because of its limited curability.

PMID- 17235046
TI  - Induction chemoradiation and surgical resection for superior sulcus non-small
      cell lung carcinomas: long-term results of Southwest Oncology Group Trial 9416
      (Intergroup Trial 0160).
AB  - PURPOSE: Traditional treatment for superior sulcus non-small-cell lung cancers
      (SS NSCLC), radiation plus surgery, yields a 50% rate of complete resection and a
      30% 5-year survival. On the basis of improved outcomes in other subsets of stage
      III NSCLC, this trial tested the feasibility of induction chemoradiotherapy for
      SS NSCLC. PATIENTS AND METHODS: Patients with T3-4, N0-1 SS NSCLC received two
      cycles of cisplatin and etoposide concurrently with radiation (45 Gy). Patients
      with stable or responding disease underwent thoracotomy. All patients received
      two more cycles of chemotherapy. Survival was calculated by the Kaplan-Meier
      method and prognostic factors were assessed by Cox regression analysis. RESULTS:
      From April 1995 to November 1999, 110 eligible patients (76 men, 34 women) were
      entered onto the study (78 T3, 32 T4 tumors). Induction therapy was completed by
      104 (95%) patients. Of 95 patients eligible for surgery, 88 (80%) underwent
      thoracotomy, two (1.8%) died postoperatively, and 83 (76%) had complete
      resection. Pathologic complete response (CR) or minimal microscopic disease was
      seen in 61 (56%) resection specimens. Five-year survival was 44% for all patients
      and 54% after complete resection, with no difference between T3 and T4 tumors.
      Pathologic CR led to better survival than when any residual disease was present
      (P = .02). Disease progression occurred mainly in distant sites. CONCLUSION: This
      combined-modality approach is feasible and is associated with high rates of
      complete resection and pathologic CR in both T3 and T4 tumors. Local control and
      overall survival seem markedly improved relative to previous studies of radiation
      plus resection.

PMID- 17235047
TI  - Peritumoral fibroblast SPARC expression and patient outcome with resectable
      pancreatic adenocarcinoma.
AB  - PURPOSE: SPARC (secreted protein acidic and rich in cysteine) is a protein
      involved in cell matrix interactions, wound repair, and cell migration, and has
      been reported to inhibit cancer growth. SPARC undergoes epigenetic silencing in
      many pancreatic cancers, but stromal fibroblasts adjacent to infiltrating
      pancreatic adenocarcinomas frequently express SPARC. We evaluated the prognostic
      significance of tumor and peritumoral SPARC expression in patients with
      pancreatic adenocarcinoma. PATIENTS AND METHODS: The expression patterns of SPARC
      were characterized by immunohistochemistry in 299 primary pancreatic ductal
      adenocarcinoma resection specimens from patients who underwent
      pancreaticoduodenectomy at Johns Hopkins Hospital (Baltimore, MD) between 1998
      and 2003. Kaplan-Meier analysis and Cox proportional hazards regression modeling
      were used to assess the mortality risk associated with the presence or absence of
      tumor SPARC and peritumoral SPARC status. RESULTS: By Kaplan-Meier analysis,
      patients whose pancreatic cancer stromal fibroblasts expressed SPARC (median
      survival, 15 months) had a significantly worse prognosis than patients whose
      tumor stroma did not express SPARC (median survival, 30 months; log-rank P <
      .001). In contrast, the expression of SPARC in pancreatic cancer cells was not
      associated with prognosis (log-rank P = .13). Controlling for other prognostic
      factors (tumor size, positive lymph nodes, margin status, tumor grade, and age),
      the relative hazard for patients whose stroma expressed SPARC compared with those
      whose stroma did not was 1.89 (95% CI, 1.31 to 2.74); the expression of SPARC in
      pancreatic cancer cells remained unrelated to prognosis (relative hazard, 1.02;
      95% CI, 0.73 to 1.42). CONCLUSION: The expression of SPARC by peritumoral
      fibroblasts portends a poorer prognosis for patients with pancreatic cancer.

PMID- 17235048
TI  - Impact of chemoradiotherapy after disease control with chemotherapy in locally
      advanced pancreatic adenocarcinoma in GERCOR phase II and III studies.
AB  - PURPOSE: The management of locally advanced (LA) pancreatic cancer patients
      remains controversial. To select patients who could benefit from
      chemoradiotherapy (CRT), the therapeutic strategy used by the Groupe Cooperateur
      Multidisciplinaire en Oncologie (GERCOR) consisted of initial chemotherapy (CT)
      for at least 3 months. The decision to administer CRT or continue CT in
      nonprogressive patients was the investigator's choice. PATIENTS AND METHODS:
      Retrospective analysis of outcome in 181 patients with LA pancreatic cancer (76
      women and 105 men; mean age, 61 years; range, 37 to 85 years) enrolled onto
      prospective phase II and III GERCOR studies was performed to compare the survival
      of patients who received CRT with that of patients who continued CT alone.
      RESULTS: Median progression-free survival (PFS) and overall survival (OS) times
      for the 181 patients were 6.3 and 11.4 months, respectively. Fifty-three patients
      (29.3%) had metastatic disease after 3 months of CT and were not eligible for
      CRT. Among the 128 remaining patients (70.3%) who had no disease progression and
      who were, therefore, eligible for CRT, 72 (56%) received CRT (group A), whereas
      56 (44%) continued with CT (group B). The two groups were balanced for initial
      characteristics (performance status, sex, age, and type of CT), as well as for
      induction CT results. In groups A and B, the median PFS times were 10.8 and 7.4
      months, respectively (P = .005), and the median OS times were 15.0 and 11.7
      months, respectively (P = .0009). CONCLUSION: These results suggest that, after
      control of disease by initial CT, CRT could significantly improve survival in
      patients with LA pancreatic cancer compared with CT alone. A prospective phase
      III study is ongoing to evaluate this strategy.

PMID- 17235049
TI  - Final results of a prospective clinical trial with VAMP and low-dose involved
      field radiation for children with low-risk Hodgkin's disease.
AB  - PURPOSE: To evaluate outcome and assess complications in children and adolescents
      with low-risk Hodgkin's disease treated with vinblastine, doxorubicin,
      methotrexate, and prednisone (VAMP) chemotherapy and low-dose, involved-field
      radiation therapy (IFRT). PATIENTS AND METHODS: One hundred ten children with low
      risk Hodgkin's disease were treated with four cycles of VAMP and 15 Gy IFRT for
      those who achieved a complete response (CR) or 25.5 Gy for those with a partial
      response after two cycles of VAMP. RESULTS: With median follow-up of 9.6 years
      (range, 1.7 to 15.0), 5- and 10-year overall survival were 99.1% and 96.1%,
      respectively, and 5-and 10-year event-free survival (EFS) were 92.7% and 89.4%.
      Factors contributing to 10-year EFS were: early CR (P = .02), absence of B
      symptoms (P = .01), lymphocyte predominant histologic subtype (P = .04), and less
      than three initial sites of disease (P = .02). Organ toxicity has been limited to
      correctable hypothyroidism in 42% of irradiated patients, and one case of cardiac
      dysfunction. Seventeen healthy babies have been born to 106 survivors. There have
      been two malignant tumors: one thyroid cancer within the radiation therapy field
      and one Ewing's sarcoma outside the radiation therapy field. CONCLUSION: Risk
      adapted, combined-modality therapy using VAMP chemotherapy with radiation is
      effective and well tolerated. Pediatric patients with low-risk Hodgkin's disease
      can be cured with therapy without an alkylating agent, bleomycin, etoposide, or
      high-dose, extended-field radiotherapy. Thus, these children are expected to
      retain normal fertility, organ function, and be at low risk of a second malignant
      tumor.

PMID- 17235050
TI  - Interactions with the investment industry: practical and ethical implications.

PMID- 17235051
TI  - Hand-foot and stump syndrome to sorafenib.

PMID- 17235052
TI  - Massive cervical and abdominal lymphadenopathy caused by localized amyloidosis.

PMID- 17235053
TI  - Hematologic and cytogenetic spontaneous remission in acute monocytic leukemia
      (FAB M5b) with trisomy 8.

PMID- 17235054
TI  - Sexual health in adolescents.

PMID- 17235055
TI  - Iron and zinc deficiency in children in developing countries.

PMID- 17235056
TI  - Tuberculosis in resource poor countries.

PMID- 17235057
TI  - Surgery for cataract.

PMID- 17235058
TI  - Renaming schizophrenia.

PMID- 17235059
TI  - Proposal strikes at the heart of medicine.

PMID- 17235060
TI  - Fundamental problem is not lack of preventive care.

PMID- 17235061
TI  - Community matrons do make a difference.

PMID- 17235062
TI  - Government should have respected evidence.

PMID- 17235063
TI  - Seats must be secured when children are not using them.

PMID- 17235064
TI  - Make surgeons more active in teaching anatomy at all levels.

PMID- 17235065
TI  - The best time to die (to help fellow taxpayers).

PMID- 17235067
TI  - Lack of hospital beds causes emergency departments to miss targets.

PMID- 17235068
TI  - Democrats push for stem cell research in US.

PMID- 17235069
TI  - UK regulatory body wants public consultation on human-animal hybrid research.

PMID- 17235070
TI  - Government suffers its first defeat over Mental Health Bill.

PMID- 17235071
TI  - Compulsive gamblers must get free NHS treatment, BMA says.

PMID- 17235072
TI  - One in four trainee doctors have concerns about their NHS career, study shows.

PMID- 17235073
TI  - NHS is accused of "appalling lack of workforce planning".

PMID- 17235074
TI  - Group asks US National Institutes of Health to reveal industry ties.

PMID- 17235075
TI  - Fertilisation authority raids controversial fertility clinics.

PMID- 17235076
TI  - Plan to halve MRSA cases by 2008 is probably not achievable, memo says.

PMID- 17235077
TI  - EU is urged to press for global ban on mercury.

PMID- 17235078
TI  - Arabian Peninsula states launch plan to eradicate malaria.

PMID- 17235080
TI  - GMC accuses doctor of handing out slimming pills "as if they were Smarties".

PMID- 17235089
TI  - What have we learnt from Vioxx?

PMID- 17235090
TI  - No quick fix for the NHS.

PMID- 17235092
TI  - Today's doctor's dilemma.

PMID- 17235093
TI  - Graphical method for depicting randomised trials of complex interventions.

PMID- 17235094
TI  - The in-between world of knowledge brokering.

PMID- 17235095
TI  - Syphilis.

PMID- 17235096
TI  - Redesign and modernisation of an NHS cataract service (Fife 1997-2004):
      multifaceted approach.
AB  - PROBLEM: A Scottish national health service ophthalmic facility was unable to
      cope with increasing demand for cataract surgery. DESIGN: Multifaceted approach
      to redesign hospital space to accommodate a cataract unit; to invest in cataract
      nursing staff to allow more operations under local anaesthesia and as day cases;
      and to enhance input by general practitioners and optometrists to streamline and
      reduce false positive cataract referrals. A prospective audit for productivity
      was undertaken in 2004 (two years after the redesign) and compared against the
      national cataract surgery audit data for Fife from 1997. SETTING: District
      general hospital serving a population of 400,000 in south east Scotland. KEY
      MEASURES FOR IMPROVEMENT: Increasing throughput of cataract surgery while
      assessing quality of care provided against predefined evidence and Royal College
      of Ophthalmologists' guidelines, and evaluating training standards for ophthalmic
      surgical trainees against higher surgical training requirements. STRATEGIES FOR
      CHANGE: Cataract services were redesigned to increase throughput and to reduce
      waiting times while preserving the quality of patient care. A secondary end point
      was to maintain surgical case load mix thus allowing trainees to continue to
      fulfil the number of operations required to acquire higher surgical training
      standards. EFFECTS OF CHANGE: In the same three month period 237 cataract
      operations were carried out in 1997 and 374 in 2004, representing an increase of
      productivity by 60%. The waiting time for surgery decreased from more than one
      year to three months. The redesign resulted in almost complete preoperative and
      postoperative assessment by nursing staff, thus freeing medical time and allowing
      for more operations. Optometrists' referrals with reports increased significantly
      (P<0.0001). The number of operations carried out as day cases under local
      anaesthesia increased, with fewer intraoperative complications and postoperative
      visits (P<0.0001). The number of operations carried out by trainees more than
      doubled, from 43 to 100 cases, thus improving training opportunities. LESSONS
      LEARNT: Modest capital investment in rebuilding space and in staff for cataract
      services can improve the quality and volume of cataract surgery. Enhancing
      existing NHS services provides for future need while maintaining training
      standards, thus potentially obviating the need for independent treatment centres.
      This model could be used throughout the United Kingdom.

PMID- 17235097
TI  - Collapse with loss of awareness.

PMID- 17235098
TI  - Don't use minocycline as first line oral antibiotic in acne.

PMID- 17235106
TI  - Admission plasma leptin level strongly correlates with the success of
      thrombolytic therapy in patients with acute myocardial infarction.
AB  - Obesity-associated alterations in coagulation and fibrinolytic factors in favor
      of thrombosis are well known. Observations suggest that leptin, a recently
      discovered obesity gene product, in addition to being a satiety factor, induces
      platelet aggregation, accelerates formation of firm thrombi, and is associated
      with abnormal fibrinolysis. The authors studied the influence of plasma leptin
      concentrations on admission within 6 hours of acute myocardial infarction (MI) on
      the outcome of thrombolytic therapy (TT). Forty-one patients with acute MI who
      underwent TT were enrolled into the study. Levels of plasma leptin were
      determined with radioimmunoassay method in samples obtained just before
      initiation of TT. Patients were initially classified according to the admission
      plasma leptin concentrations, and it was observed that failure of reperfusion
      therapy with streptokinase was significantly higher in patients with admission
      plasma leptin concentrations > or =14 ng/mL (group 2) as compared to patients
      with admission plasma leptin concentrations <14 ng/mL (group 1). Final failure of
      TT, identified both by reinfarction and absence of early reperfusion as assessed
      noninvasively, was observed in 11 patients (39%) in group 1 and in 10 patients
      (77%) in group 2 (p=0.025). Left ventricular ejection fraction was slightly but
      significantly higher in group 1 than in group 2 (p=0.031). High plasma leptin
      concentrations on admission in patients within 6 hours after the onset of acute
      MI are associated with less TT efficacy. The authors suggest that admission
      leptin levels may play a role in the management of patients with acute MI.

PMID- 17235107
TI  - The effect of ACE gene polymorphisms on Doppler blood flow parameters of carotid
      and brachial arteries in patients with myocardial infarction.
AB  - The authors investigated the relationship between the angiotensin-converting
      enzyme (ACE) insertion/deletion (I/D) polymorphism and the blood flow
      characteristics of common carotid (CCA) and brachial arteries (BA) by color
      Doppler ultrasound (CDUS) in patients with acute anterior myocardial infarction
      (AAMI). Sixty four patients (11 women and 53 men), aged 25 to 77 years, with AAMI
      were studied. The ACE genotypes were established. Peak-systolic (PSV) and end
      diastolic velocity (EDV) of right and left CCA, PSV of right BA, and intimal
      medial thickness (IMT) of both CCAs were measured by CDUS. All results were
      evaluated statistically. The ACE genotypes were distributed as follows: 43.8% DD,
      43.8% ID, and 12.5% II. PSVs of BA and both CCAs were lower in patients with DD
      and ID than with II (p<0.05). EDVs of both CCAs were also lower in the same
      groups, but statistically not significant (p>0.05). IMTs of both CCAs did not
      differ among patients with various ACE genotypes (p>0.05). These results suggest
      that ACE I/D polymorphism influences Doppler blood flow parameters of both BA and
      CCA, but does not affect IMT of CCA.

PMID- 17235108
TI  - Serum NT-proBNP concentrations in the early phase do not predict the severity of
      systolic or diastolic left ventricular dysfunction among patients with ST
      elevation acute myocardial infarction.
AB  - The cohort included 55 consecutive patients with first ST elevation acute
      myocardial infarction (STEAMI) who underwent reperfusion. Blood samples were
      drawn for N-terminal pro B-type natriuretic peptide (NT-proBNP), highly-sensitive
      C-reactive protein (hs-CRP), creatinine kinase (CK), cardiac troponin l (cTnl),
      and white blood cell (WBC) count within 24 hours of admission. Transthoracic
      echocardiography, performed within the same time frame, assessed left ventricular
      (LV) systolic function, as well as diastolic function. Variables significantly
      associated with poor systolic LV dysfunction were hs-CRP, peak CK, cTnl, and WBC.
      There was no significant correlation between NT-proBNP and systolic function
      early after STEAMI (p=0.49). Among patients with diastolic dysfunction, there was
      no significant correlation between NT-proBNP levels and peak mitral E-wave
      velocity to peak initial A-wave velocity (E/A ratio) (r =0.19, p=0.18) or E-wave
      deceleration time (r =0.22, p=0.15). Thus, NT-proBNP levels in the early phase
      after STEAMI were not indicative of systolic or diastolic function.

PMID- 17235109
TI  - Contribution of plasma lipid disturbances to vascular endothelial function in
      patients with slow coronary flow.
AB  - Previous studies have suggested that microcirculatory abnormalities cause slow
      coronary flow (SCF). However, the underlying mechanism of this phenomenon has not
      yet been well documented. Therefore, the aim of this study was to determine the
      role of plasma lipid disturbances in pathogenesis of slow coronary flow (SCF).
      Forty patients with SCF (group I) and 37 subjects with normal coronary arteries
      (group II) were included in the study. In each subject plasma lipid
      concentrations (total cholesterol [TC], low-density lipoprotein cholesterol [LDL
      C], high-density lipoprotein cholesterol [HDL-C], and triglyceride [TG]) and
      brachial artery flow-mediated dilatation (FMD) and nitroglycerin (NTG)-induced
      dilatation were measured. Total cholesterol level was found to be similar in the
      2 groups. In group I, HDL-C level was lower than in group II (34 +/-3 vs 40 +/-4
      mg/dL, p=0.0001). In group I, TG level was higher than in group II (213 +/-29 vs
      198 +/-24 mg/dL p=0.002). In group I, FMD was smaller than that of group II (3.48
      +/-3.1% vs 10.4 +/-5.6%, p=0.0001). The percent NTG-induced dilatation was not
      different between the groups (15.5 +/-5.3% vs 17.3 +/-6.9%, p=0.27). On
      regression analysis; there was a significant relationship between percent of FMD
      and HDL-C (r =0.65, p=0.0001). When the 2 groups were analyzed separately, HDL-C
      was still related to percent of FMD in both groups (r =0.47 p=0.002 and r =0.45
      p=0.005, respectively). Multivariate regression analysis showed that only plasma
      HDL-C was independently related to FMD (F=7.5 p=0.0001). In patients with SCF,
      reduced flow-mediated dilatation was detected and was found to be associated with
      plasma lipid disturbances, principally low HDL and high TG levels.

PMID- 17235110
TI  - Differences in vascular reactivity between men and women.
AB  - The purpose of this study was to compare the gender and age-related differences
      in vascular reactivity in healthy men and women across a wide age range. Fifty
      seven men and 61 women between 20 and 89 years of age, free of cardiovascular
      disease and risk factors, were categorized into younger (20-39 years), middle
      aged (40-59 years), and older (60-89 years) age groups. Subjects were
      characterized on body weight and height, body mass index (BMI), and calf blood
      flow under resting, postocclusive reactive hyperemic (PORH), and maximal
      hyperemic conditions in the lower extremity with use of venous occlusion mercury
      strain-gauge plethysmography. Similar baseline characteristics were observed
      among age groups, whereas men had greater body weight (p<0.05), higher BMI values
      (p<0.05), and a trend toward higher ankle-brachial index (ABI) values (p=0.054)
      than women. While calf blood flow measurements were similar for men and women at
      rest and at maximal hyperemic conditions, women had a greater percentage change
      in calf blood flow from rest to PORH than men (p=0.046). After adjusting for body
      weight, BMI, and ABI, the percentage change in calf blood flow from rest to PORH
      was no longer significantly higher in the women (p>0.05). Furthermore, the
      percentage change in calf blood flow from rest to PORH was negatively related to
      body weight (r = -0.30, p<0.01) and to BMI (r = -0.26, p<0.01) in the men and
      women. No differences (p>0.05) in the calf blood flow measures were observed
      among the age groups. In a healthy cohort free of cardiovascular disease,
      increased BMI accounted for poorer vascular reactivity in men compared to women
      regardless of age.

PMID- 17235111
TI  - Intermediate postchallenge hyperglycemia in overweight and obese subjects: a new
      marker of impaired glucose regulation?
AB  - The objective of this study was to compare subjects with intermediate
      postchallenge hyperglycemia (INPH) to those with normal glycemic status, impaired
      fasting glucose (IFG), and/or impaired glucose tolerance (IGT), as well as type 2
      diabetes mellitus. Furthermore, the authors evaluated the impact of INPH on
      target organ damage. In total, 487 overweight and obese adults (BMI > or =27
      kg/m(2)), 252 men and 235 women, mean age 52.9 +/-10.2 years, were studied. All
      participants underwent a clinical and laboratory evaluation, as well as an oral
      glucose tolerance test (OGTT). They were also investigated by echocardiography,
      carotid ultrasonography, and pulse wave analysis. Overall, 302 (62%) subjects had
      normal glycemic status, 64 (13.1%) had IFG and/or IGT, 95 (19.5%) had type 2
      diabetes mellitus, and 26 (5.4%) had INPH. Individuals with INPH had an increased
      index of insulin resistance (higher homeostasis model assessment-insulinogenic
      index [HOMA-IR], p<0.0001), impaired insulin secretion (lower insulinogenic
      index, p<0.0001), and higher glycosylated hemoglobin (HbA(1c)) levels (p<0.0001)
      in comparison with the normoglycemic subjects, but not to those with IFG and/or
      IGT or diabetes (p = 0.6). No difference was observed concerning the risk factors
      studied, left ventricular mass and vascular remodeling, among subjects with INPH,
      IFG and/or IGT, and diabetes. However, individuals with INPH had a higher
      proportion of echolucent carotid artery plaques in comparison with the
      normoglycemic subjects (p = 0.04) and those with IFG and/or IGT (p = 0.01).
      Intermediate postchallenge hyperglycemia seems to represent a new category of
      glucose metabolism disturbances with increased atherogenic impact. Therefore,
      evaluating intermediate glucose levels in an OGTT could contribute to better
      identify overweight individuals at risk of developing diabetes mellitus and
      cardiovascular events.

PMID- 17235112
TI  - Left atrial anatomy and function after conversion from atrial fibrillation in
      hypertrophic hearts.
AB  - The aim of the study was to evaluate the influence of left ventricular (LV)
      hypertrophy on left atrial (LA) electrical and mechanical function after
      cardioversion atrial fibrillation (A-Fib) of brief duration. Study group A
      included 100 patients with a first diagnosis of hypertension who had a moderate
      LV hypertrophy. The patient population included 64 men and 36 women with a mean
      age of 55 +/-7 years who were hospitalized because of A-Fib and were cardioverted
      with external DC shock. Control group B included 100 patients without cardiac
      hypertrophy cardioverted because of lone A-Fib. Atrial function and size were
      assessed by Doppler echocardiography and the following parameters were measured:
      transmitral peak A velocity, atrial filling fraction, atrial ejection force, peak
      E velocity, deceleration time, and isovolumic relaxation time, LA maximal and
      minimal volume, and LV cardiac mass index. Baseline echocardiography showed that
      LA diameters and volumes were enlarged in all patients during A-Fib. After the
      restoration of sinus rhythm LA diameters and volumes decreased and the reduction
      was more evident in group B compared to group A. LA function as a continuous
      variable was negatively related to LV mass index (r = -0.77), LA diameter (r = 
      0.66 and r = -0.69 for the superoinferior diameter), LA maximal volume (r = 
      0.61) and LA minimal volume (r = -0.55) (all p<0.01). Atrial ejection force as a
      continuous variable was positively related to age (r =0.78), peak A wave velocity
      (r =0.71), systolic blood pressure (r =0.51), and IVRT (r =0.41) (all p<0.01).
      Hypertrophy influenced the recovery of atrial function after cardioversion of A
      Fib. Atrial function was reduced in patients with LV hypertrophy even after A-Fib
      of brief duration.

PMID- 17235113
TI  - Percutaneous balloon aortic valvuloplasty: a new look at an old procedure: a case
      report.
AB  - There has been little change in the technical approach to balloon aortic
      valvuloplasty (BAV) over the last two decades. Large-caliber sheaths and extra
      stiff wires have been used routinely to accommodate the large balloons used for
      this purpose. Consequently the morbidity (and possibly mortality) rates have been
      high. With the recent advances in the interventional hardware, a new look at the
      current approach to BAV is justified. In this report we describe an 89-year-old
      woman with critical aortic stenosis who underwent rapid and successful BAV by the
      use of a single 8-French arterial sheath, a regular (and not stiff) wire, and one
      peripheral balloon. We conclude that BAV can be done easily and safely with the
      technique and equipment described in this case report.

PMID- 17235114
TI  - Management of a patient with a null low-density lipoprotein receptor mutation: a
      case report.
AB  - A 13-year-old Greek boy with severe dyslipidemia, large tuberous xanthomas over
      the knees and elbows, Achilles' tendon xanthomas, and a bilateral corneal arcus
      was referred to the Lipid Clinic. He had a supravalvular aortic stenosis, 50% to
      60% stenosis of both carotid arteries, and normal coronary arteries. Familial
      hypercholesterolemia was clinically diagnosed. A V408M null low-density
      lipoprotein receptor (LDLR) mutation was identified in homozygosity. He responded
      to lipid-lowering drugs by decreasing total cholesterol by 32%, low-density
      lipoprotein cholesterol by 33%, and triglyceride levels by 30%. Additional
      treatment with low-density lipoprotein-apheresis further decreased total
      cholesterol by 52%, low-density lipoprotein cholesterol by 55%, and triglycerides
      by 43%. Low-density lipoprotein cholesterol levels between apheresis sessions
      showed a declining pattern. A significant regression of tuberous xanthomas was
      noted. A suitable combination of lipid-lowering drugs is effective even in this
      case of homozygosity for a null LDLR mutation. Furthermore, the coadministration
      of statins, cholestyramine, and ezetimibe during low-density lipoprotein
      apheresis tends to counterbalance the postapheresis relapse in low-density
      lipoprotein cholesterol levels.

PMID- 17235115
TI  - Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or
      amyloid-beta peptide levels in vivo.
AB  - ABCA1-deficient mice have low levels of poorly lipidated apolipoprotein E (apoE)
      and exhibit increased amyloid load. To test whether excess ABCA1 protects from
      amyloid deposition, we crossed APP/PS1 mice to ABCA1 bacterial artificial
      chromosome (BAC) transgenic mice. Compared with wild-type animals, the ABCA1 BAC
      led to a 50% increase in cortical ABCA1 protein and a 15% increase in apoE
      abundance, demonstrating that this BAC supports modest ABCA1 overexpression in
      brain. However, this was observed only in animals that do not deposit amyloid.
      Comparison of ABCA1/APP/PS1 mice with APP/PS1 controls revealed no differences in
      levels of brain ABCA1 protein, amyloid, Abeta, or apoE, despite clear retention
      of ABCA1 overexpression in the livers of these animals. To further investigate
      ABCA1 expression in the amyloid-containing brain, we then compared ABCA1 mRNA and
      protein levels in young and aged cortex and cerebellum of APP/PS1 and
      ABCA1/APP/PS1 animals. Compared with APP/PS1 controls, aged ABCA1/APP/PS1 mice
      exhibited increased ABCA1 mRNA, but not protein, selectively in cortex.
      Additionally, ABCA1 mRNA levels were not increased before amyloid deposition but
      were induced only in the presence of extensive Abeta and amyloid levels. These
      data suggest that an induction of ABCA1 expression may be associated with late
      stage Alzheimer's neuropathology.

PMID- 17235116
TI  - Model-based compartmental analysis indicates a reduced mobilization of hepatic
      vitamin A during inflammation in rats.
AB  - Vitamin A (VA) kinetics was studied in rats with marginal VA stores before,
      during, and after inflammation. Rats received orally [11,12-(3)H(N)]retinol
      ([(3)H]VA; day 0), and inflammation was induced on day 21 with lipopolysacchride
      (LPS) for 3 days (n = 5) or recombinant human interleukin-6 (rhIL-6) for 7 days
      (n = 5). Both the fraction of [(3)H]VA and retinol concentrations in plasma were
      reduced significantly by LPS or rhIL-6. Compartmental analysis using the Windows
      version of Simulation, Analysis, and Modeling software was applied to group mean
      data, and non-steady-state models were developed. After absorption, VA kinetics
      was described by a three-compartment model that included plasma,
      kidney/interstitium, and liver/carcass. Four mechanisms decreasing plasma retinol
      were investigated: increased urinary excretion, increased irreversible loss,
      increased movement into interstitium, and decreased hepatic mobilization.
      Modeling demonstrated that a 79% reduction in hepatic mobilization of retinol
      (from 4.3 to 0.9 nmol/h) by 15 h after LPS best accounted for the observed
      changes in plasma VA kinetics (sum of squares = 9.05 x 10(-07)). rhIL-6 caused an
      earlier reduction (75% by 5.6 h). These models predicted a return to control
      values by 10 days after inflammation. If prolonged, inflammation-induced
      hyporetinolemia can render hepatic retinol unavailable to extrahepatic tissues,
      possibly leading to their impaired function, as observed in VA-deficient children
      with measles infection.

PMID- 17235117
TI  - Myopathic (not neuropathic) electrophysiological abnormalities in dynamin 2
      related centronuclear myopathy.

PMID- 17235119
TI  - Persistent hand movement representations in the brains of amputees.

PMID- 17235120
TI  - Language functions in right-hemisphere damage and schizophrenia: apparently
      similar pragmatic deficits may hide profound differences.

PMID- 17235123
TI  - Establishing the genetic heterogeneity of familial hemiplegic migraine.

PMID- 17235125
TI  - Olfactory dysfunction in patients with narcolepsy with and without REM sleep
      behaviour disorder.
AB  - Patients with idiopathic rapid eye movement sleep behaviour disorder (RBD)
      frequently develop Parkinson's disease and the majority present with hyposmia,
      which is a potential preclinical non-motor sign of Parkinson's disease.
      Accordingly, it has been proposed that the clinical symptoms of hyposmia and RBD
      in combination have to be considered as very early symptoms of Parkinson's
      disease. Since not only patients with idiopathic RBD but also patients in whom
      RBD is associated with narcolepsy present with an olfactory dysfunction we
      investigated if hyposmia in RBD patients with concomitant narcolepsy is RBD
      specific or if narcolepsy per se is associated with olfactory dysfunction. We
      studied olfactory function in 20 narcoleptic patients each with RBD (9 male and
      11 female; mean age 45.4 +/- 14.0 years, range 20-75 years) and without
      associated RBD (8 male and 12 female; mean age 44.4 +/- 13.40 years, range 20-70
      years) and 40 age- and gender-matched healthy control subjects using standardized
      'Sniffin' Sticks'. Both, narcoleptics with (Narc/+RBD) and without RBD (Narc/
      RBD) had a significantly higher olfactory threshold (Narc/+RBD, P = 0.0001; Narc/
      RBD, P = 0.0001), lower discrimination scores (P = 0.001; P = 0.014) and lower
      identification scores (P = 0.057; P = 0.003) than controls. There were no
      symptoms or signs for early parkinsonism in both patient groups. Our results show
      for the first time that narcolepsy per se is associated with olfactory
      dysfunction. In contrast to patients with idiopathic RBD, hyposmia in patients
      with RBD associated with narcolepsy is unlikely to be a predictor for developing
      parkinsonism.

PMID- 17235124
TI  - Hereditary multi-infarct dementia of the Swedish type is a novel disorder
      different from NOTCH3 causing CADASIL.
AB  - Several hereditary small vessel diseases (SVDs) of the brain have been reported
      in recent years. In 1977, Sourander and Walinder described hereditary multi
      infarct dementia (MID) in a Swedish family. In the same year, Stevens and
      colleagues reported chronic familial vascular encephalopathy in an English family
      bearing a similar phenotype. These disorders have invariably been suggested to be
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leucoencephalopathy (CADASIL) but their genetic identities remain unknown. We
      used molecular, radiological and neuropathological methods to characterize these
      disorders. Direct DNA sequencing unexpectedly confirmed that affected members of
      the English family carried the R141C mutation in the NOTCH3 gene diagnostic of
      CADASIL. However, we did not detect any pathogenic mutations in the entire 8091
      bp reading frame of NOTCH3 or find clear evidence for NOTCH3 gene linkage in the
      Swedish DNA. This was consistent with the lack of hyperintense signals in the
      anterior temporal pole and external capsule in Swedish subjects upon magnetic
      resonance imaging. We further found no evidence for granular osmiophilic material
      in skin biopsy or post-mortem brain samples of affected members in the Swedish
      family. In addition, there was distinct lack of NOTCH3 N-terminal fragments in
      the cerebral microvasculature of the Swedish hereditary MID subjects compared to
      the intense accumulation in the English family afflicted with CADASIL. Several
      differences in arteriosclerotic changes in both the grey and white matter were
      also noted between the disorders. The sclerotic index values, density of collagen
      IV immunoreactivity in the microvasculature and number of perivascular
      macrophages were greater in the English CADASIL samples compared to those from
      the Swedish brains. Multiple approaches suggest that the Swedish family with
      hereditary MID suspected to be CADASIL has a different novel disorder with
      dissimilar pathological features and belongs to the growing number of genetically
      uncharacterized familial SVDs.

PMID- 17235126
TI  - Restoration of normal motor control in Parkinson's disease during REM sleep.
AB  - Although normal subjects do not move during REM sleep, patients with Parkinson's
      disease may experience REM sleep behaviour disorder (RBD). The characteristics of
      the abnormal REM sleep movements in RBD have, however, not been studied. We
      interviewed one hundred consecutive non-demented patients with Parkinson's
      disease and their bed partners using a structured questionnaire assessing the
      presence of RBD. They rated the quality of movements, voice and facial expression
      during RBD as being better, equal or worse than in awake ON levodopa condition.
      Night-time sleep and movements were video-monitored during polysomnography in 51
      patients to evaluate the presence of bradykinesia, tremor and hypophonia during
      REM sleep. Fifty-nine patients had clinical RBD with 53/59 bed partners able to
      evaluate them. All 53 (100%) reported an improvement of at least one component of
      motor control during RBD. By history, movements were improved in 87% patients
      (faster, 87%; stronger, 87%; smoother, 51%), speech was better in 77% patients
      (more intelligible, 77%; louder, 38%; better articulated, 57%) and facial
      expression was normalized in 47% patients. Thirty-eight per cent of bed partners
      reported that movements were 'much better', even in the most disabled patients.
      The video-monitored purposeful movements in REM sleep were also surprisingly
      fast, ample, coordinated and symmetrical, without obvious sign of parkinsonism.
      The movements were, however, jerky, violent and often repetitive. While all
      patients had asymmetrical parkinsonism when awake, most of the time they used the
      more disabled arm, hand and leg during the RBD (P = 0.04). Movements involved six
      times as often the upper limbs and the face as the lower limbs (OR: 5.9, P =
      0.004). The percentage of time containing tremor EMG activity decreased with
      sleep stages from 34.9 +/- 15.5% during wakefulness, to 3.6 +/- 5.7% during non
      REM sleep stages 1-2, 1.4 +/- 3.0% during non-REM sleep stages 3-4, and 0.06 +/-
      0.2% during REM sleep (in this last case, it was subclinical tremor). The
      restored motor control during REM sleep suggests a transient 'levodopa-like'
      reestablishment of the basal ganglia loop. Alternatively, parkinsonism may
      disappear by REM sleep-related disjunction between pyramidal and extrapyramidal
      systems. We suggest the following model: the movements during the RBD would be
      generated by the motor cortex and would follow the pyramidal tract bypassing the
      extrapyramidal system. These movements would eventually be transmitted to lower
      motor neurons because of brainstem lesions interrupting the pontomedullary
      pathways which mediate the REM sleep atonia.

PMID- 17235127
TI  - Depletion of putative chemosensitive respiratory neurons in the ventral medullary
      surface in multiple system atrophy.
AB  - Multiple system atrophy (MSA) is a disorder that may manifest with reduced
      respiratory chemosensitivity and central sleep apnoea. Chemosensitive
      glutamatergic and serotonergic neurons located just beneath the ventral medullary
      surface, corresponding to the human arcuate nucleus (ArcN), have recently been
      implicated in control of automatic breathing in response to hypercapnia and
      hypoxia. We sought to determine whether these neurons were affected in MSA.
      Medullae were obtained at post-mortem from 11 patients (8 men, 3 women, age 64 +/
      3 years) with neuropathologically confirmed MSA and 11 control subjects (6 men
      and 5 women, age 66 +/- 4 years). Fifty micrometre sections obtained throughout
      the medulla were processed for vesicular glutamate transporter-2 (VGLUT-2),
      tryptophan-hydroxylase (TrOH), glial fibrillary acid protein (GFAP) and alpha
      synuclein immunoreactivity. Cell counts, GFAP immunoreactivity and presence of
      glial cytoplasmic inclusions (GCIs) were assessed in the ArcN. In MSA, compared
      with controls, there was a marked depletion of ArcN neurons immunoreactive for
      either VGLUT-2 (74 +/- 21 versus 342 +/- 84 cells/section, P < 0.004) or TrOH (5
      +/- 1 versus 16 +/- 2 cells/section, P < 0.001). There was also marked astrocytic
      gliosis and accumulation of alpha-synuclein immunoreactive GCIs in the ventral
      medullary surface in all cases. Our results indicate that there is severe loss of
      putative chemosensitive glutamatergic and serotonergic neurons as well as marked
      astrocytic gliosis in the ventral medullary surface in MSA. This may provide a
      possible morphological basis for impaired respiratory chemosensitivity and
      central sleep apnoea in this disorder.

PMID- 17235128
TI  - Solvent type affects the number, distribution, and relative quantities of
      volatile compounds found in sweet whey powder.
AB  - This study compares the performance of diethyl ether, methylene chloride, methyl
      formate, and pentane in the analysis of volatile flavor components in sweet whey
      powder. Extracts were prepared from sweet whey powder using each solvent.
      Volatile components were isolated by solvent extraction followed by solvent
      assisted flavor evaporation. Gas chromatography-mass spectroscopy, coelution with
      known standards, and retention indices were used to identify the volatile
      compounds. Sixty total compounds were either positively or tentatively identified
      across all 4 solvents, but the number, distribution between the molecular
      classes, and relative quantities detected depended on solvent type. The highest
      number, widest distribution, and greatest relative quantities were found using
      methylene chloride and methyl formate, whereas diethyl ether and especially
      pentane were noticeably less effective. Results are characterized using molecular
      based characteristics of solvents and solutes including dipole moment, dielectric
      constant, Log P (octanol-water partition coefficient), polarizability, water
      solubility, and Lewis acidity/basicity. Polarity and acidity/basicity were the
      primary factors that determined solvent performance. This work establishes a
      molecular-level basis for the selection of solvents in the analysis of sweet whey
      powder flavors.

PMID- 17235129
TI  - Binding of aflatoxin M1 to different protein fractions in ovine and caprine milk.
AB  - The affinity of aflatoxin M1 toward the main milk protein fractions in ewe and
      goat milk was investigated by using an ELISA. This study took into account the
      possible effects of common dairy processes such as ultrafiltration, acidic or
      rennet curding, and production of ricotta from acidic or rennet whey. Treatments
      that allowed the separation of casein from whey proteins under conditions that do
      not alter the physical or chemical status of the proteins (such as
      ultracentrifugation) were used as a reference. None of the treatments used in
      typical dairy processes caused significant release of the toxin, in spite of the
      relevant changes they induced in the interactions among proteins. Only the
      combined heat and acidic treatment used for production of ricotta cheese altered
      the structure of whey proteins to the point where they lost their ability to bind
      the toxin. This study also showed that, regardless of the physical state of the
      sample, a commercial electronic nose device, in combination with appropriate
      statistical tools, was able to discriminate among different levels of sample
      contamination.

PMID- 17235130
TI  - Bovine alpha-lactalbumin stimulates mucus metabolism in gastric mucosa.
AB  - Bovine alpha-lactalbumin (alpha-LA), a major milk protein, exerts strong
      gastroprotective activity against rat experimental gastric ulcers induced by
      ethanol or stress. To elucidate the mechanisms underlying this activity, the
      influence of alpha-LA on gastric mucus metabolism was investigated in vitro and
      in vivo. For the in vitro study, RGM1 cells (a rat gastric epithelial cell line)
      were selected for observation of the direct activity of alpha-LA on gastric
      mucosal cells and cultured in the presence of either alpha-LA or ovalbumin (OVA),
      a reference protein showing no gastroprotective activity. Amounts of synthesized
      and secreted mucin, a major component of mucus, were determined using
      [3H]glucosamine as a tracer, and prostaglandin E2 (PGE2) levels in the culture
      medium were determined by RIA. For the in vivo study, the thickness of the mucus
      gel layer, a protective barrier for gastric mucosa, was evaluated histochemically
      in rat gastric mucosa. alpha-Lactalbumin (3 mg/mL) significantly stimulated mucin
      synthesis and secretion in RGM1 cells and also increased PGE2 levels in the
      culture medium. In contrast, OVA showed no enhancing effects under identical
      conditions. Neither indomethacin, a cyclo-oxygenase inhibitor, nor AH23848, a
      prostaglandin EP4 receptor antagonist, affected alpha-LA-induced enhancement of
      mucin synthesis and secretion. In vivo, oral administration of alpha-LA (300
      mg/kg x 3 times/d x 7 d) increased the thickness of the mucus gel layer in rats.
      These results indicate that alpha-LA fortifies the mucus gel layer by stimulating
      mucin production and secretion in gastric mucus-producing cells, and that this
      enhancing effect is independent of endogenous PGE2. Comparison of the efficacy of
      alpha-LA with OVA suggests that the activities observed in RGM1 cells are closely
      related to the gastroprotective effects in rat gastric ulcer models. In
      conclusion, alpha-LA stimulates mucus metabolism, and this action may be
      responsible for its gastroprotective activity.

PMID- 17235131
TI  - Antioxidant nature of bovine milk beta-lactoglobulin.
AB  - Heating is necessary for processing milk in the dairy industry, which evidently
      produces a conformational change in beta-lactoglobulin (beta-LG). beta
      Lactoglobulin, a major protein that accounts for approximately 10 to 15% of total
      milk proteins, is a globular protein consisting of 162 AA with a relative
      molecular mass of 18.4 kDa. The purpose of the present study was to determine the
      antioxidant role of beta-LG in milk and the possible mechanism involved. We
      showed that beta-LG is a mild antioxidant whose potency is less than that of
      vitamin E and probucol (the latter being an antioxidant used for clinical
      therapy). The conversion of the beta-LG monomer to dimer was responsible, in
      part, for the mode of action in protecting low-density lipoproteins against
      copper-induced oxidation. Cross-linking the free thiol groups of beta-LG by
      heating (100 degrees C for 2 min), or chemically modifying the beta-LG by
      carboxymethylation to block the thiol groups resulted in a substantial loss of
      antioxidant activity. The data suggest that Cys-121 plays an essential role in
      the antioxidant nature of beta-LG. By using an anti-LG antibody affinity column
      to deplete the beta-LG from milk, we observed from the lost antioxidant activity
      that beta-LG contributes approximately 50% of the total activity. Because beta-LG
      is extremely sensitive to thermal denaturation, to maintain its antioxidant
      nature, dairy products consumed daily should not be overheated in order to
      maintain its antioxidant nature.

PMID- 17235132
TI  - Study on the influence of pasture on volatile fraction of ewes' dairy products by
      solid-phase microextraction and gas chromatography-mass spectrometry.
AB  - The detection of markers of identification of the geographical origin of food is
      an attractive challenge and, as far as dairy products are concerned, this paper
      represents a contribution to this field. In this research the influence of feed
      on the volatile compound composition was investigated on milk, 2-mo-old cheese
      (Caciotta), and whey cheese (ricotta) obtained from the same flock of Sarda ewes,
      under standardized technological conditions. Three different types of pasture
      (mixture of Lolium perenne and Trifolium squarrosum; rough pasture; Avena sativa)
      were studied. Solid-phase microextraction combined with gas chromatography-mass
      spectrometry was used and principal component analysis was applied for
      statistical evaluation of the data set. The volatile composition was
      significantly affected by the type of pasture independently of the type of cheese
      and the ripening period. Moreover, a marker of rough pasture, tentatively
      identified as (E,E)-3,7,11-tri-methyl-2,4,10-dodecatriene, was detected only in
      milk and cheeses produced when the ewe flock grazed on that pasture.

PMID- 17235133
TI  - Dairy powder rehydration: influence of protein state, incorporation mode, and
      agglomeration.
AB  - A simplified method to study rehydration was used on different dairy powders. The
      method involved dispersing powder in a stirred vessel equipped with a turbidity
      sensor. The changes of turbidity occurring during powder rehydration highlighted
      the rehydration stage, and the influence of the proteins' state on rehydration
      was clarified. Casein powders had a quick wetting time but very slow dispersion,
      making the total rehydration process time-consuming. On the other hand, whey
      powders were found to have poor wettability but demonstrated immediate dispersion
      after wetting. Mixing casein (80%) and whey (20%) before spray drying greatly
      improved rehydration time compared with casein powder; whereas mixing whey powder
      with casein powder at the same ratio after spray drying caused a dramatic
      deterioration in the rehydration properties. Moreover, agglomeration was found to
      significantly improve the rehydration time of whey protein powder and to slow
      down the rehydration time of casein powder. These opposite effects were related
      to the rate-controlling stage (i.e., wetting stage for whey protein and
      dispersion stage for casein).

PMID- 17235134
TI  - Effect of beta-lactoglobulin A and B whey protein variants on the rennet-induced
      gelation of skim milk gels in a model reconstituted skim milk system.
AB  - The effect of fortifying reconstituted skim milk with increasing levels of the
      beta-lactoglobulin (beta-LG) genetic variants A, B, and an A-B mixture on rennet
      induced gelation was studied by small deformation-sensitive rheology. Free-zone
      capillary electrophoresis and high-sensitivity oscillatory rheology were used to
      elucidate the role of potential heterotypic associative interactions between whey
      proteins and casein in a mixed colloidal system, subjected to moderate heating
      (65 degrees C for 30 min) prior to renneting, on the gelling properties of the
      system. Increasing levels of added whey protein, in the concentration range of
      0.225 to 1.35% of added protein, led to a concomitant progressive increase in the
      equilibrium shear storage modulus, G' (recorded after approximately 10,800 s), in
      the order beta-LG B > beta-LG A and beta-LG A-B, as the general expected
      consequence of the setup of denser casein gel networks. The preferential effect
      of beta-LG B over beta-LG A on the mechanical strength of the gels may be due to
      the formation of cross-links and aggregates involving whey proteins and rennet
      hydrolysis products or an increase in the size of the casein micelle caused by
      the grafting of beta-LG B to its surface, or both. The results of free-zone
      capillary electrophoresis were consistent with the notion that beta-LG B (and not
      beta-LG A) binds to the casein micelle under an optimal stoichiometry of 1:0.045
      (mg/mg), even in the absence of heat treatment. The liquid-like character of the
      gel networks formed, tan delta, was a parameter sensitive to the level of
      addition of beta-LG A in particular. At low concentrations (up to 0.45%) of beta
      LG A, tan delta increased by almost twice as much, which was interpreted as a
      result of the increase in the loss modulus, G'', of the sol fraction because of
      the presence of unbound beta-LG A. At greater incremental concentrations of beta
      LG (>0.45%), the formation of smaller whey protein aggregates confined to the sol
      fraction may have led to a progressive decrease in tan delta. The critical gel
      time, t(gel), was also affected by the concentration of added whey protein and
      described 3 zones of behavior, irrespective of the type of whey protein variant.
      The critical gel time was slightly shorter for beta-LG B than for beta-LG A at
      0.45% of added whey protein, but this difference became larger at 0.67%. Even
      when only beta-LG B was found to associate with casein prior to renneting, both
      beta-LG A and beta-LG B, either alone or mixed, had a profound influence on the
      mechanical strength and coagulation kinetics of the rennet-induced casein gels.
      This knowledge is expected to be useful to exert better control and optimize
      processing conditions during the manufacturing of cheese and cheese analogs.

PMID- 17235135
TI  - Enzymatic interesterification of tripalmitin with vegetable oil blends for
      formulation of caprine milk infant formula analogs.
AB  - The structure of triacylglycerols in vegetable oil blends was enzymatically
      modified, and the blends were incorporated into skim caprine milk to produce goat
      milk-based infant formula analogs, homologous to human milk. A modified lipid
      containing palmitic, oleic, and linoleic acids, resembling the composition of
      human milk fat, was synthesized by enzymatic interesterification reactions
      between tripalmitin and a vegetable oil blend containing a 2.5:1.1:0.8 ratio of
      coconut, safflower, and soybean oils. A commercial sn-1,3-specific lipase
      obtained from Rhyzomucor miehei, Lipozyme RM IM, was used as the biocatalyst. The
      effects of substrate molar ratio and reaction time on the incorporation of
      palmitic, oleic, and linoleic acids at the sn-2 position of the triacylglycerols
      were investigated. The fatty acid composition and sn-2 position of the
      experimental formulas were analyzed using gas chromatography. Results showed that
      the highest incorporation of palmitic acid was obtained at 12 h of incubation at
      55 degrees C with a substrate molar ratio of 1:0.4 of tripalmitin to vegetable
      oil blend. However, the modified milk interesterified for 12 h at a 1:1 molar
      ratio had a greater resemblance to human milk compared with the other formulas.
      The level of oleic acid incorporation at the sn-2 position increased with the
      molar ratio of tripalmitin to vegetable oil blend. It was concluded that, unlike
      the original goat milk and other formulas, the formulated caprine milk with a
      molar ratio of 1:1 and a 12-h incubation was similar to the fatty acid
      composition of human milk.

PMID- 17235136
TI  - Lipolysis and proteolysis of modified and producer milks used for calibration of
      mid-infrared milk analyzers.
AB  - Our objective was to determine if lipolysis or proteolysis of calibration sets
      during shelf life influenced the mid-infrared (MIR) readings or calibration
      slopes and intercepts. The lipolytic and proteolytic deterioration was measured
      for 3 modified milk and 3 producer milk calibration sets during storage at 4
      degrees C. Modified and producer milk sets were used separately to calibrate an
      optical filter and virtual filter MIR analyzer. The uncorrected readings and
      slopes and intercepts of the calibration linear regressions for fat B, fat A,
      protein, and lactose were determined over 28 d for modified milks and 15 d for
      producer milks. It was expected that increases in free fatty acid content and
      decreases in the casein as a percentage of true protein of the calibration milks
      would have an effect on the MIR uncorrected readings, calibration slopes and
      intercepts, and MIR predicted readings. However, the influence of lipolysis and
      proteolysis on uncorrected readings was either not significant, or significant
      but very small. Likewise, the amount of variation accounted for by day of storage
      at 4 degrees C of a calibration set on the calibration slopes and intercepts was
      also very small. Most of the variation in uncorrected readings and calibration
      slopes and intercepts were due to differences between the optical filter and
      virtual filter analyzers and differences between the pasteurized modified milk
      and raw producer milk calibration sets, not due to lipolysis or proteolysis. The
      combined impact of lipolysis and proteolysis on MIR predicted values was <0.01%
      in most cases.

PMID- 17235138
TI  - Effect of somatic cell count on Prato cheese composition.
AB  - The objective of this research was to evaluate the effect of 2 levels of somatic
      cell counts (SCC) in raw milk on Prato cheese composition, protein and fat
      recovery, cheese yield, and ripening. A 2 x 6 factorial design with 3
      replications was performed in this study: 2 levels of SCC and 6 levels of storage
      time. Initially, 2 groups of dairy cows were selected to obtain low (<200,000
      cells/ mL) and high (>600,000 cells/mL) SCC in milks that were used to
      manufacture 2 vats of cheese: 1) low SCC and 2) high SCC. Milk, whey, and cheese
      compositions were evaluated; clotting time was measured; and cheese yield,
      protein recovery, and fat recovery were calculated. The cheeses were evaluated
      after 5, 12, 19, 26, 33, and 40 d of ripening according to pH, moisture, pH 4.6
      soluble nitrogen, 12% trichloroacetic acid soluble nitrogen as a percentage of
      total nitrogen, and firmness. High-SCC milk presented significantly higher total
      protein and nonprotein nitrogen and lower true protein and casein concentrations
      than did low-SCC milk, indicating an increased whey protein content and a higher
      level of proteolysis. Although the pH of the milk was not affected by the somatic
      cell level, the cheese obtained from high-SCC milk presented significantly higher
      pH values during manufacture and a higher clotting time. No significant
      differences in cheese yield and protein recovery were observed for these levels
      of milk somatic cells. The cheese from high-SCC milk was higher in moisture and
      had a higher level of proteolysis during ripening, which could compromise the
      typical sensory quality of the product.

PMID- 17235137
TI  - Valuation of milk composition and genotype in cheddar cheese production using an
      optimization model of cheese and whey production.
AB  - A mass balance optimization model was developed to determine the value of the
      kappa-casein genotype and milk composition in Cheddar cheese and whey production.
      Inputs were milk, nonfat dry milk, cream, condensed skim milk, and starter and
      salt. The products produced were Cheddar cheese, fat-reduced whey, cream, whey
      cream, casein fines, demineralized whey, 34% dried whey protein, 80% dried whey
      protein, lactose powder, and cow feed. The costs and prices used were based on
      market data from March 2004 and affected the results. Inputs were separated into
      components consisting of whey protein, ash, casein, fat, water, and lactose and
      were then distributed to products through specific constraints and retention
      equations. A unique 2-step optimization procedure was developed to ensure that
      the final composition of fat-reduced whey was correct. The model was evaluated
      for milk compositions ranging from 1.62 to 3.59% casein, 0.41 to 1.14% whey
      protein, 1.89 to 5.97% fat, and 4.06 to 5.64% lactose. The kappa casein genotype
      was represented by different retentions of milk components in Cheddar cheese and
      ranged from 0.715 to 0.7411 kg of casein in cheese/kg of casein in milk and from
      0.7795 to 0.9210 kg of fat in cheese/kg of fat in milk. Milk composition had a
      greater effect on Cheddar cheese production and profit than did genotype. Cheese
      production was significantly different and ranged from 9,846 kg with a high
      casein milk composition to 6,834 kg with a high-fat milk composition per 100,000
      kg of milk. Profit (per 100,000 kg of milk) was significantly different, ranging
      from $70,586 for a high-fat milk composition to $16,490 for a low-fat milk
      composition. However, cheese production was not significantly different, and
      profit was significant only for the lowest profit ($40,602) with the kappa-casein
      genotype. Results from this model analysis showed that the optimization model is
      useful for determining costs and prices for cheese plant inputs and products, and
      that it can be used to evaluate the economic value of milk components to optimize
      cheese plant profits.

PMID- 17235139
TI  - Associations among body condition score, body weight, somatic cell count, and
      clinical mastitis in seasonally calving dairy cattle.
AB  - The objective of this study was to determine if an association existed among body
      condition score (BCS), body weight (BW), and udder health, as indicated by
      somatic cell score (SCS) and cases of clinical mastitis (CM). The data consisted
      of 2,635 lactations from Holstein-Friesian (n = 523) and Jersey (n = 374) cows in
      a seasonal calving pasture-based research herd between the years 1986 and 2000,
      inclusive. Increased BCS at calving was associated with reduced SCS in first- and
      second-parity cows, and greater SCS in cows of third parity or greater. This
      relationship persisted for most BCS traits throughout lactation. Body weight was
      positively associated with SCS, although the effect was greater in Jersey cows
      than in Holstein-Friesians. Increased BCS and BW loss in early lactation were
      associated with lower SCS and a reduced probability of a high test-day SCC. Body
      condition score was not significantly related to CM with the exception of a
      curvilinear relationship between the daily rate of BCS change to nadir and CM in
      early lactation. Several BW variables were positively associated with a greater
      likelihood of CM. Nevertheless, most associations with udder health lacked
      biological significance within the ranges of BCS and BW generally observed on
      farm. Results are important in assuring the public that modern dairy systems,
      where cows are subjected to substantial amounts of BCS mobilization in early
      lactation, do not unduly compromise cow udder health.

PMID- 17235140
TI  - Relationships among milk production, energy balance, plasma analytes, and
      reproduction in Holstein-Friesian cows.
AB  - Associations were examined between components and indicators of early lactation
      energy balance (EB) and measures of fertility in Holstein cows. Milk production,
      dry matter intake (DMI), body condition score (BCS), and endocrine and metabolite
      data from 96 cows were analyzed using multivariate logistic regression and
      survival analysis. Fertility variables investigated were interval to commencement
      of luteal activity (C-LA), calving to conception interval (CCI), and conception
      rate to first service (CON1). Mean daily EB, milk protein content, and DMI during
      the first 28 d in milk were associated positively with CON1. Cows having poorer
      BCS (< or =2.25) at first service had a lower CON1. Positive associations were
      identified among EB, milk protein content, DMI, and the likelihood of a shorter
      interval to C-LA. Cows having greater DMI and a more positive EB had an increased
      likelihood of a shorter CCI, whereas a lower nadir BCS was associated with an
      increased likelihood of a longer CCI. Milk yield was not associated with any of
      the fertility variables investigated. A greater plasma concentration of insulin
      like growth factor I (IGF-I) during the first 2 wk of lactation was associated
      with a greater CON1 and an increased likelihood of a shorter interval to C-LA. In
      conclusion, we identified DMI as the principal component of EB influencing
      subsequent fertility. Furthermore, results indicate that milk protein content and
      plasma IGF-I concentration in early lactation may be useful indicators of
      reproductive efficiency.

PMID- 17235141
TI  - Production effects of pathogens causing bovine leukosis, bovine viral diarrhea,
      paratuberculosis, and neosporosis.
AB  - The primary purpose of this research was to determine associations among
      seropositivity for bovine leukemia virus (BLV), bovine viral diarrhea virus
      (BVDV), Mycobacterium avium ssp. paratuberculosis (MAP), and Neospora caninum
      (NC) and each of 3 outcome variables (305-d milk, fat, and protein production) in
      Canadian dairy cattle. Serum samples from up to 30 randomly selected cows from
      342 herds on monthly milk testing were tested for antibodies against BLV (IDEXX
      ELISA; IDEXX Corporation, Westbrook, ME), MAP (IDEXX or Biocor ELISA; Biocor
      Animal Health, Inc., Omaha, NE), and NC (IDEXX or Biovet ELISA; Biovet Inc., St.
      Hyacinthe, Quebec, Canada). Up to 5 unvaccinated cattle over 6 mo of age were
      tested for virus-neutralizing antibodies to the Singer strain of type 1 BVDV.
      Dairy Herd Improvement records were obtained electronically for all sampled cows.
      Linear mixed models with herd and cow as random variables were fit, with
      significant restricted maximum likelihood estimates of outcome effects being
      obtained, while controlling for potential confounding variables. Bovine leukemia
      virus seropositivity was not associated with 305-d milk, 305-d fat, or 305-d
      protein production. Cows in BVDV-seropositive herds (at least one unvaccinated
      animal with a titer > or =1:64) had reductions in 305-d milk, fat, and protein of
      368, 10.2, and 9.5 kg, respectively, compared with cows in BVDV-seronegative
      herds. Mycobacterium avium ssp. paratuberculosis seropositivity was associated
      with lower 305-d milk of 212 kg in 4+-lactation cows compared with MAP
      seronegative 4+-lactation cows. Neospora caninum seropositivity in primiparous
      cows was associated with lower 305-d milk, fat, and protein of 158, 5.5, and 3.3
      kg, respectively, compared with NC-seronegative primiparous cows. There were no
      interactions among seropositivity for any of the pathogens and their effects on
      any of the outcomes examined, although the low MAP seroprevalence limited this
      analysis. Results from this research will contribute to understanding the
      economic impacts of these pathogens and justify their control.

PMID- 17235142
TI  - Gait pattern of heifers before and after claw trimming: a high-speed
      cinematographic study on a treadmill.
AB  - The manner in which the claws contacted the ground at the walk was evaluated in
      18 healthy heifers. The animals were filmed before and after claw trimming while
      walking on a treadmill using high-speed cinematography (500 frames/s). For each
      limb, 4 consecutive steps were recorded from a side and a frontal plane. The
      objectives of the study were to evaluate 1) the order of claw contact with the
      treadmill surface, 2) the initial claw contact area, and 3) the effect of
      trimming on claw contact patterns. The heifers placed their front feet on the
      ground in a plane sagittal to the shoulders, whereas the hind feet were advanced
      more toward the median plane. Before trimming, the lateral claws contacted the
      ground before the medial in 83% of front and 100% of hind limbs. Trimming changed
      the percentage to 92% in the front and to 97% in the hind limbs. The percentage
      with which the heel of the lateral claws became the region of initial contact
      with the ground increased from 47 to 64% in the front feet and from 50 to 78% in
      the hind feet. In the medial claws of the forelimbs, claw trimming shifted the
      region of initial contact from the toe to the abaxial wall and heel. In the hind
      limbs, the main region of initial contact of the medial claws became the abaxial
      wall. Weight bearing by the medial claw became visibly apparent only during the
      midstance, propulsion, and push-off phases. "Heel first" contact of the lateral
      claws in the front and hind limbs may be the normal gait pattern in cattle. On
      hard surfaces, this pattern may lead to overload and predispose to disease,
      especially in the hind limbs.

PMID- 17235143
TI  - Short communication: Ability of cultured mammary epithelial cells in a bicameral
      system to secrete milk fat.
AB  - Mammary epithelial cells from lactating cows were cultured onto inserts coated
      with type I collagen. Every second day, the rates of fatty acid synthesis and
      secretion were determined by measuring the amount of [14C]-labeled sodium acetate
      incorporated into lipids over a 4-h period. The [14C]-containing lipids were
      identified by thin layer chromatography fractionation. In parallel, the integrity
      of the cell layer was evaluated by measurement of transepithelial electrical
      resistance. The integrity increased progressively to reach a maximum after 8 d of
      culture. Cells incorporated acetate into lipids; 1.34% of acetate was
      incorporated into lipids produced by freshly isolated cells. This percentage
      decreased to 0.5% after 2 d of culture. Moreover, this capacity decreased with
      the duration in culture; on d 8, the rate of incorporation dropped to about 3% of
      that on d 2. In the cell extracts, the [14C]-labeled lipids were mainly
      triglycerides, although the proportion of diglycerides and phospholipids
      progressively increased as a part of total newly synthesized lipids. The
      proportion of triglycerides decreased 0.66 times between d 2 and 8 when the
      proportion of diglycerides and phospholipids increased 1.33 and 2.18 times,
      respectively. About 28% of the newly synthesized lipids were secreted within 4 h
      of incubation. Around 65 to 85% of these labeled lipids were found in the apical
      compartment, suggesting a partially vectorial secretion. But 58 to 80% of labeled
      lipids found in the apical and basolateral medium were free fatty acids.
      Functional tight junctions and incorporation of labeled fatty acids into
      triglycerides are not compatible with an inferred status of complete
      dedifferentiation of the cell layer. Moreover, triglyceride secretion seems
      compromised, probably due to the lack of an appropriate cell environment and cell
      shape.

PMID- 17235144
TI  - Incontinentia lactis: physiology and anatomy conducive to milk leakage in dairy
      cows.
AB  - Incontinentia lactis is a possible predisposing factor for an elevated level of
      intramammary infection. The goal of the present study was to investigate possible
      causes of incontinentia lactis in dairy cows. Two farms that differed in breed
      composition, but that had similar average milk yields were studied: herd A, 28
      kg/d, 31 Red Holstein cows; and herd B, 26 kg/d, 16 Brown Swiss cows. Herd A was
      classified into 2 groups: incontinentia lactis (ILA group) and control, whereas
      herd B was exclusively a control herd. Milk samples that represented foremilk and
      the main milk fraction were collected during 4 milking sessions. In addition,
      milk leakage samples from the ILA group were collected at different time
      intervals from 0 to 5 h before milking. Measurements of the teat, milk flow,
      fractions of cisternal and alveolar milk, intramammary pressure, and blood
      oxytocin pattern also were obtained. The ILA cows did not have differences in fat
      content between milk leakage and cisternal milk fraction. Milk fat content,
      however, increased during milking in response to continuous milk ejection (1.95,
      1.99, and 4.61% for milk leakage, cisternal, and main milk samples,
      respectively). Teat canals were 9% shorter in the ILA cows, which showed greater
      milk yield, peak, and average flow rates. Quarter cisternal milk yield of ILA
      cows tended to be greater (0.50 vs. 0.23 and 0.28 kg for ILA and controls from
      herds A and B, respectively), whereas percentages of cistern milk and alveolar
      milk did not differ from controls. The greater pressure in the ILA group, both
      before and after manual udder stimulation (ILA: 4.0 and 6.4 kPa; control: 2.0 and
      5.0 kPa, respectively), could be an important cause for the leakage.
      Nevertheless, the increase in IMP that occurred after udder preparation affirms
      that milk ejection occurred in response to the tactile teat stimulation, but not
      before the onset of leakage. Blood oxytocin concentration in ILA cows was low
      until the start of udder preparation and increased in response to the milking
      stimulus (reaffirming the hypothesis that milk leakage occurred in the absence of
      milk ejection). In conclusion, milk losses by leakage are likely due to the large
      amount of cisternal milk, which creates pressure and causes leakage, in the
      absence of milk ejection.

PMID- 17235145
TI  - Timed artificial insemination of two consecutive services in dairy cows using
      prostaglandin F2alpha and gonadotropin-releasing hormone.
AB  - Timed artificial insemination (TAI) protocols use PGF(2alpha) and GnRH injections
      to synchronize ovulation. The objective was to evaluate the PGPG protocol (d 0,
      PGF(2alpha); d 3, GnRH; d 11, PGF(2alpha); d 13, GnRH and TAI) for first TAI and
      also examine methods for second TAI in nonpregnant cows. A factorial test of the
      first PGF(2alpha) and first GnRH injections within the PGPG protocol was
      performed (the last PGF(2alpha) and GnRH injections were deemed essential to the
      TAI). Lactating dairy cows (n = 804) in a commercial herd were assigned to 1 of 5
      first-TAI treatments, which were PGPG, GPG (d 0, no treatment; d 3, GnRH; d 11,
      PGF(2alpha); d 13, GnRH and TAI), PPG (d 0, PGF(2alpha); d 3, no treatment; d 11,
      PGF(2alpha); d 13, GnRH and TAI), and PG (d 0, no treatment; d 3, no treatment; d
      11, PGF(2alpha); d 13, GnRH and TAI); the Ovsynch protocol (GnRH, 7 d,
      PGF(2alpha), 2 d, GnRH and TAI) was the positive control. For resynchronization,
      cows received either GnRH or the control (no injection) on d 22 after TAI.
      Nonpregnant cows on d 28 were then treated with PGF(2alpha) on d 29, GnRH on d
      31, and TAI [i.e., resynchronization treatments of ReGPG (received GnRH on d 22)
      and RePG (did not receive GnRH on d 22)]. Pregnancy rates for PGPG, GPG, PPG, PG,
      and Ovsynch were similar at d 28 after first TAI. Analyses of multiple
      explanatory factors by logistic regression detected an effect of uterine or
      ovarian abnormality on the d-28 pregnancy rate (normal more likely to be
      pregnant). Day-42 pregnancy rates were affected by uterine or ovarian abnormality
      (normal more likely to be pregnant), postpartum disease occurrence (healthy cows
      more likely to be pregnant), milk production, and days in milk. Treatment was not
      significant for the d-42 pregnancy rate. Effects of postpartum disease, milk
      production, and days in milk on the d-42 pregnancy rate were apparently
      manifested through their effects on embryonic loss between d 28 and 42 of
      pregnancy. High-producing cows that received TAI early postpartum were most
      likely to experience embryonic loss. Day-42 pregnancy rates after the
      resynchronization treatment were affected by an interaction of the first
      synchronization treatment with the resynchronization treatment. We concluded that
      although PGPG can be used for TAI, a simpler TAI protocol that includes the last
      2 injections (PGF(2alpha), 2 d; GnRH and TAI) would be equally effective.

PMID- 17235146
TI  - Effect of photoperiod in the third trimester of gestation on milk production and
      circulating hormones in dairy goats.
AB  - Multiparous Israeli Saanen goats (n = 8) were blocked at dry off (approximately
      45 d prepartum) into 2 treatments of 4 goats each based on body weight (BW),
      previous milk production, and the number of detected embryos in utero. Treatments
      consisted of long-day (16 h light:8 h dark) and short-day (8 h light:16 h dark)
      photoperiods at normothermic ambient temperature (22 degrees C, 72% relative
      humidity). All goats were returned to ambient photoperiod after kidding, milked
      twice daily, and milk yield was automatically recorded. Dry matter intake was
      similar between treatments and averaged 980 g/d. Milk production was greater in
      the short-day than in the long-day treatment (2,932 vs. 2,320 g/d) during the 12
      wk experimental period. Milk protein and lactose contents were similar in both
      treatments and averaged 3.61 and 4.88%, respectively, whereas milk fat was
      greater in the long-day treatment (4.80 vs. 4.22%). Plasma insulin-like growth
      factor 1 was greater in the long-day treatment (149 vs. 73 ng/mL) during the dry
      period than in the short-day treatment, but was similar postkidding, averaging 76
      ng/mL. Concentrations of triiodothyronine in plasma were similar in both
      treatments during the dry period, but greater during lactation in the short-day
      treatment (122.1 vs. 94.1 ng/mL). Plasma prolactin was greater in the long-day
      than in the short-day treatment during the dry period (28.0 vs. 17.5 ng/mL),
      whereas it was similar throughout lactation (11.7 ng/mL). These data support the
      idea that greater milk production in goats exposed to short days during the dry
      period is not explained by differences in feed intake or increased secretion of
      insulin-like growth factor 1.

PMID- 17235147
TI  - Factors affecting the concentration of sphingomyelin in bovine milk.
AB  - Sphingomyelin is a phospholipid located in the outer leaflet of the plasma
      membrane of most cells and is a component of the milk fat globule membrane.
      Sphingomyelin and its digestion products participate in several antiproliferative
      pathways that may suppress oncogenesis. Although milk and dairy products are
      important sources of sphingomyelin in the human diet, little is known about
      factors that influence sphingomyelin concentrations in milk fat or whether
      concentrations can be modified via the nutrition of cows. Sphingomyelin
      concentrations were determined in milk from Holstein and Jersey cows matched for
      parity and stage of lactation. Sphingomyelin was more concentrated in milk fat
      from Holstein cows than in milk fat from Jersey cows (1,044 vs. 839 microg/g of
      fat). Concentrations in whole milk did not differ because of greater milk fat
      content for milk from Jerseys. Differences between breeds may be related to the
      greater fat globule size in milk from Jerseys. Sphingomyelin content in whole
      milk increased with increasing days in milk because of associated increases in
      milk fat content. Regardless of breed, primiparous cows had greater amounts of
      stearic acid and less palmitic acid in sphingomyelin than did older cows. The
      sphingomyelin concentration in milk fat of cows in a commercial Jersey herd was
      lower for cows in their fourth or greater parity. Sphingomyelin content in whole
      milk was greater for cows in late lactation because of greater milk fat content.
      Feed restriction of multiparous Holstein cows to 37% of ad libitum dry matter
      intake increased milk fat content but did not affect milk sphingomyelin content
      or milk fat globule size. Supplementation of the diet with 4% soybean oil did not
      affect milk composition, sphingomyelin content, or milk fat globule size. Milk
      was sampled seasonally from 7 herds throughout Illinois during a 2-yr period.
      Sphingomyelin concentration in milk fat was greatest during summer and least
      during winter, but whole milk concentrations did not vary across seasons. We
      conclude that 1) sphingomyelin content of milk fat is greater in milk from
      Holsteins than that from Jerseys, 2) sphingomyelin content in whole milk
      increases with stage of lactation, and 3) sphingomyelin content of milk fat is
      greater during summer. However, efforts to produce milk with a greater
      sphingomyelin content through altering management and nutrition are unlikely to
      be successful.

PMID- 17235148
TI  - The milk yield response to frequent milking in early lactation of dairy cows is
      locally regulated.
AB  - Frequent milking during early lactation of dairy cows increases milk production
      throughout lactation; however, whether this response is regulated systemically
      via lactogenic hormones, locally in the mammary gland, or both is unknown. We
      hypothesized that the effects of frequent milking on milk production during early
      lactation are regulated via local mechanisms. Ten multiparous cows were assigned
      at parturition to unilateral frequent milking [UFM; twice daily milking of the
      left udder half (2x), or 4 times daily milking of the right udder half (4x)] for
      d 1 to 21 of lactation. After treatment, cows were milked twice daily for the
      remainder of lactation. At the first milking after calving, milk yield from
      individual quarters was measured to verify that udder halves produced equal
      amounts of milk prior to treatment. Thereafter, individual quarters were milked
      on d 3 and 7, weekly for the first 5 wk of lactation, and once every 3 mo for the
      remainder of lactation. During UFM, cows produced 3.9 +/- 0.7 kg/d more from the
      side milked 4x than the side milked 2x. Upon cessation of treatment, milk
      production from the side milked 4x decreased, but remained at 1.8 +/- 0.5 kg/d
      more than the side milked 2x for the remainder of lactation. After milk yield was
      corrected to the equivalent of a whole-udder basis, acute milk yield responses to
      frequent milking were found to be consistent with previous reports. Moreover, we
      observed greater persistency in the milk yield response, which lasted throughout
      lactation. We conclude that both immediate and persistent effects on milk
      production of frequent milking during early lactation are regulated at the level
      of the mammary gland. Our results demonstrate that UFM is a valid and efficient
      model for investigating the effects of frequent milking during early lactation in
      dairy cows.

PMID- 17235149
TI  - Effects of a supplement containing trans-10, cis-12 conjugated linoleic acid on
      bioenergetic and milk production parameters in grazing dairy cows offered ad
      libitum or restricted pasture.
AB  - Conjugated linoleic acid (CLA) reduces milk fat synthesis in grazing dairy cows
      and may improve calculated net energy balance (EBAL). Study objectives were to
      determine whether CLA-induced milk fat depression could be utilized during times
      of feed restriction to improve bioenergetic and milk production parameters.
      Twelve multiparous rumen-fistulated Holstein cows (204 +/- 7 d in milk) were
      offered ad libitum (AL) or restricted (R) pasture and abomasally infused twice
      daily with 0 (control) or 50 g/d of CLA (CLA; mixed isomers) in a 2-period
      crossover design. Treatment periods lasted 10 d and were separated by a 10-d
      washout period. Milk and plasma samples were averaged from d 9 and 10, and EBAL
      was calculated from d 6 to 10 of the infusion period. Pasture restriction reduced
      the yield of milk (3.9 kg/d) and milk components. The CLA treatment reduced milk
      fat yield by 44 and 46% in AL and R, respectively. There was no effect of CLA on
      milk yield or milk lactose content or yield in either feeding regimen; however,
      CLA increased the milk protein content and yield by 7 and 6% and by 5 and 8%, in
      AL and R, respectively. The CLA-induced changes to milk fat and protein doubled
      the protein:fat ratio in both AL and R. Calculated EBAL improved following the
      CLA infusion (-0.44 vs. 2.68 and 0.38 vs. 3.29 Mcal/d for AL and R,
      respectively); however, CLA did not alter plasma bioenergetic markers. Data
      indicate that during short periods of nutrient limitation, supplemental CLA may
      be an alternative management tool to enhance protein synthesis and improve the
      milk protein:fat ratio and calculated EBAL in cows grazing pasture. Further
      studies are required to determine whether CLA is effective at improving
      bioenergetic and production parameters during more severe or longer term nutrient
      restriction.

PMID- 17235150
TI  - Effects of dietary vitamin C on neutrophil function and responses to intramammary
      infusion of lipopolysaccharide in periparturient dairy cows.
AB  - Neutrophil function and the severity and incidence of mastitis in dairy cows is
      related to the intake of many antioxidant nutrients. Because vitamin C is the
      major water-soluble antioxidant in mammals, we examined the effect of dietary
      vitamin C on neutrophil function and responses to intramammary infusion of
      lipopolysaccahride (LPS) in periparturient dairy cows. At 2 wk before anticipated
      calving, Holstein cows were fed diets that provided 0 (16 cows) or 30 (15 cows)
      g/d of supplemental vitamin C (phosphorylated ascorbic acid). Treatments
      continued until 7 d after cows received an infusion of 10 microg of LPS into one
      quarter of the mammary gland (on average, this occurred 32 d postcalving).
      Supplementation of vitamin C increased plasma concentrations of vitamin C at
      calving, but no differences were observed in samples taken 24 h postinfusion.
      Concentrations of vitamin C in milk (24 h postinfusion) and in neutrophils
      (calving and 24 h postinfusion) were not affected by treatment, but vitamin C
      concentrations in neutrophils isolated from milk were about 3 times greater than
      concentrations in blood neutrophils. The LPS infusion did not alter
      concentrations of vitamin C in plasma or milk, suggesting that the LPS model did
      not produce the same effects as a bacterial infection of the mammary gland with
      respect to antioxidant effects. Supplemental vitamin C had no effect on
      neutrophil phagocytosis or bacterial kill. Dietary vitamin C reduced the milk
      somatic cell count but did not affect the febrile response or milk production
      following LPS infusion.

PMID- 17235151
TI  - Expression and localization of extracellular matrix-degrading proteinases and
      their inhibitors in the bovine mammary gland during development, function, and
      involution.
AB  - In degrading the extracellular matrix, matrix metalloproteinases (MMP) and the
      plasminogen activator (PA) system may play a critical role in extensive
      remodeling that occurs in the bovine mammary gland during development, lactation,
      and involution. Therefore, the aim of our study was to investigate the mRNA
      expression of MMP-1, MMP-2, MMP-14, MMP-19, tissue inhibitor of
      metalloproteinases (TIMP)-1, TIMP-2, urokinase-type PA, tissue-type PA, urokinase
      type PA receptor, and PA inhibitor-1 by quantitative PCR and to localize with
      immunohistochemistry MMP-1, MMP-2, MMP-14, and TIMP-2 proteins in the bovine
      mammary gland during pubertal mammogenesis, lactogenesis, galactopoiesis, and
      involution. Expression of mRNA for each of the studied factors was relatively
      lower during galactopoiesis and early involution but was markedly increased
      during mammogenesis and late involution, 2 stages in which tissue remodeling is
      especially pronounced. The localization of proteins for MMP-1, MMP-14, and TIMP-2
      showed a similar trend with strong staining intensity in cytoplasm of mammary
      duct and alveolar epithelial cells during pubertal mammogenesis and late
      involution. Interestingly, MMP-2 protein was localized only in the cytoplasm of
      endothelial cells during late involution. Our study demonstrated clearly that
      expression of extracellular matrix-degrading proteinases coincides with a
      concomitant expression of their inhibitors. High expression levels of MMP, TIMP,
      and PA family members seem to be a typical feature of the nonlactating mammary
      gland.

PMID- 17235152
TI  - Bovine claw and limb disorders at claw trimming related to milk yield.
AB  - As part of a cross-sectional study of Norwegian Red Cattle, associations of
      lameness, lesions at the tarsus, claw shapes, claw lesions, and claw trimming
      with milk yield were examined. Fifty-five tie-stall herds and 57 free-stall herds
      were sampled by computerized systematic selection, and 2,665 cows were trimmed
      and limb and claw disorders recorded. After exclusions, 2,599 cows were included
      in this study. Monthly recordings of milk were extracted from the Norwegian Dairy
      Herd Recording System. Most claw lesions were mild (score 1). The prevalence of
      moderate and severe lesions (score 2 and 3) did not exceed 5% for any of the
      lesions. Associations with test-day milk yield were identified using regression
      analyses (Proc Mixed) with repeated measurements within lactation and herd as
      random effect. Lactation curves were fit to visualize differences in changes in
      milk yield throughout the lactation. Milk yield was generally higher in cows with
      lesions at the tarsus, heel-horn erosions, and hemorrhages of the white line and
      the sole than in cows without these lesions, whereas cows with dermatitis yielded
      less than cows without dermatitis. Cows in lactation 1 with corkscrewed claws had
      reduced milk yield, whereas cows in lactations 2 and above had increased milk
      yield compared with cows without corkscrewed claws in respective lactations. Cows
      in lactation 1 yielded 0.47 +/- 0.15 kg and cows in later lactations yielded 0.51
      +/- 0.15 kg more milk on test days after claw trimming than they did before when
      adjusted for days in milk. In this study, where most disorders were mild, the
      most evident results were higher milk yield in cows with lesions at the tarsus,
      heel-horn erosions, and hemorrhages of the white line and the sole than in cows
      without these lesions. Cows yielded more milk after claw trimming than they did
      before trimming.

PMID- 17235153
TI  - Effect of an intramammary teat seal and dry cow antibiotic in relation to dry
      period length on postpartum mastitis.
AB  - Infusion of either a long-acting antibiotic preparation (cefalonium) or the same
      antibiotic preparation combined with an internal teat sealant (bismuth
      subnitrite) were compared for the effect on new intramammary infections at
      calving and clinical mastitis in the first 100 d of lactation, in relation to dry
      period length. For all cows, a significant reduction in the incidence of new
      infections in quarters at calving (3.7 vs. 7.3%) was found for the combination
      treatment group (150 cows) compared with the antibiotic-alone treatment (133
      cows). With a dry period of 10 wk or longer, significantly fewer new quarter
      infections (3.8 vs. 11.4%) were found in those cows receiving the combination
      treatment compared with antibiotic treatment alone. When the dry period was less
      than 10 wk, the incidence of new infections in quarters treated with the
      combination treatment was lower than for the antibiotic treatment alone (3.7 vs.
      6%) but this was not a statistically significant difference. Fewer infections
      caused by Streptococcus uberis and coagulase-negative staphylococci were found in
      cows receiving the combination treatment compared with the antibiotic treatment
      alone (not significant). Coliform isolates were less likely in cows receiving the
      combination treatment with the longer dry period but the numbers of new
      intramammary coliform infections were low for both dry period categories. Few
      infections were caused by coagulase-negative staphylococci. The incidence of
      clinical mastitis in the first 100 d of lactation in quarters infected at calving
      was significantly lower (4 vs. 15 cases) for the combination treatment than for
      the antibiotic treatment alone for both dry period lengths. The clinical
      incidence in quarters in which a pathogen was not detected in either of the
      samples taken after calving was comparable between groups. No significant
      difference was found in the total clinical incidence after calving for both
      groups irrespective of dry period length.

PMID- 17235154
TI  - Streptococcus dysgalactiae isolates at calving and lactation performance within
      the same lactation.
AB  - The objective of the study was to investigate the association between early
      lactation Streptococcus dysgalactiae isolates and milk yield, somatic cell count
      (SCC), clinical mastitis, and culling in the same lactation. The 178 commercial
      dairy herds were randomly placed into 3 penicillin- or penicillin
      dihydrostreptomycin-based dry-cow treatments and 3 different postmilking teat
      disinfection groups-negative control, iodine, or external teat sealant. All cows
      were sampled in early lactation, and Strep. dysgalactiae-positive and culture
      negative cows were followed throughout the remainder of the lactation. Mixed
      models, including repeated measurements, with test-day observation as dependent
      variable, were used to compare milk yield, SCC, and available milk quality
      variables throughout the remaining lactation. Survival analyses, using a positive
      frailty model to account for any herd random effects, were used to estimate the
      hazard ratio for clinical mastitis and culling. Streptococcus dysgalactiae
      positive cows had a significantly higher SCC throughout the lactation compared to
      culture-negative cows. For primiparous or multiparous cows, respectively, the
      differences in the geometric mean SCC between Strep. dysgalactiae-positive and
      culture-negative cows was 197,000 or 280,000 cells/mL at the beginning of the
      lactation, 24,000 or 46,000 cells/mL in mid lactation, and 39,000 or 111,000
      cells/mL at the end of the lactation. Streptococcus dysgalactiae-positive
      primiparous or multiparous cows produced 334 or 246 kg less milk, respectively,
      during a 305-d lactation compared with culture-negative cows. Compared with
      culture-negative cows, the hazard ratios for clinical mastitis in Strep.
      dysgalactiae-positive cows were 2.3 (1.9 to 2.9) and 1.6 (1.3 to 2.0) for
      culling. For cows with both Strep. dysgalactiae and Staphylococcus aureus
      isolates, the hazard ratio for culling significantly increased to 2.5 (1.9 to
      3.2).

PMID- 17235155
TI  - Parenteral treatment of clinical mastitis with tylosin base or penethamate
      hydriodide in dairy cattle.
AB  - The objective of this study was to compare the clinical and bacteriological cure
      rates of cows with clinical mastitis following treatment with either tylosin base
      (5 g injected 3 times at 24-h intervals; n = 306) or penethamate hydriodide (5 g
      injected 3 times at 24-h intervals; n = 289). Duplicate milk samples were
      collected before treatment and again 14 +/- 3 and 21 +/- 3 d later for
      microbiological analysis. Only those quarters from which gram-positive mastitis
      pathogens were isolated before treatment were included in the analyses.
      Streptococcus uberis was the most prevalent isolate. The number of cows with
      clinical failure (i.e., retreated within 21 d of enrollment) did not differ
      between treatments (64 vs. 63, respectively). At the quarter level, there was no
      difference in the proportion of bacteriological cure between treatments (81.2 vs.
      83.8% for penethamate hydriodide or tylosin, respectively). The proportions of
      clinical and bacteriological cure were influenced by age, herd, severity of
      mastitis, number of glands within the cow with clinical mastitis, bacterial
      species, and days postpartum at enrollment. There was no difference between
      treatment groups for SCC (4.46 vs. 4.44 +/- 0.08, mean +/- standard error of the
      difference in ln SCC for cows treated with penethamate hydriodide or tylosin,
      respectively) or production of milk solids (1.45 vs. 1.48 +/- 0.02 kg/d of milk
      fat + protein, for the penethamate hydriodide or tylosin treatment,
      respectively). Overall, there was no difference in the proportions of clinical
      failure (17.3 vs. 16.5% of cows treated with penethamate hydriodide or tylosin,
      respectively) or bacteriological cure (79.8 vs. 82.0% of cows treated with
      penethamate hydriodide or tylosin, respectively), or in SCC or milk production
      between dairy cows with clinical mastitis and those treated for clinical mastitis
      with 1 of 2 parenteral antibiotic therapies.

PMID- 17235156
TI  - Influence of estrus of dairy goats on somatic cell count, milk traits, and sex
      steroid receptors in the mammary gland.
AB  - Two experiments were conducted to study the effect of the stage of a spontaneous
      estrus cycle on milk yield and constituents [somatic cell count (SCC), fat,
      protein, caseins, lactose, and urea content] and on estrogen receptor-alpha
      (ERalpha ) and progesterone receptor (PR) immunostaining in the mammary gland. In
      experiment I, the major components of milk and SCC were monitored weekly in 80
      lactating Saanen goats for 6 wk, whereas detection of estrus was daily. In
      experiment II, milk samples were collected daily for SCC determination during 1
      spontaneous estrus (d 0) until the second spontaneous estrus in 14 Saanen goats.
      The day of the estrous cycle was confirmed by plasma progesterone and 17beta
      estradiol levels. Immunoreactivity of ERalpha and PR was analyzed in mammary
      gland samples of 8 Saanen goats (d 0, n = 4; d 10, n = 4) and the number of
      positive nuclei and intensity of the staining were evaluated in 1,000 cells. In
      experiment I, milk casein and protein percentages were significantly affected by
      the stage of estrous cycle; during proestrus and estrus, these variables were
      higher (3.32 +/- 0.06 and 4.44 +/- 0.08) than during metestrus (3.03 +/- 0.07 and
      4.07 +/- 0.10), but not higher than during diestrus (3.23 +/- 0.06 and 4.35 +/-
      0.09, respectively). In experiment II, daily measurement of SCC revealed higher
      levels at estrus (7,195 +/- 672 x 10(3) cells/mL) and a decline toward the luteal
      phase (1,694 +/- 672 +/- 10(3) cells/mL). Estrogen receptor-alpha and PR
      immunostaining were exclusively detected on epithelial cells. The percentage of
      positive nuclei to ERalpha was higher on d 0 than on d 10 (75.4 +/- 8.8 vs. 68.3
      +/- 8.8%), but no change was observed for PR (4.0 +/- 0.3 vs. 3.5 +/- 0.4%). The
      average immunostaining intensity for both receptors was greater on d 0 than on d
      10 (ERalpha : 1.44 +/- 0.02 vs. 1.35 +/- 0.02; PR: 0.079 +/- 0.008 vs. 0.057 +/-
      0.008). The high SCC at estrus in experiment II was associated with high plasma
      estradiol and low progesterone, suggesting that the increased SCC could be
      brought about by the estrogen-induced proliferation and exfoliation of epithelial
      cells. In addition, this action may be supported by the higher sensitivity to
      estrogens (ERalpha content) found at d 0.

PMID- 17235157
TI  - Assessment of ruminal bacterial populations and protozoal generation time in cows
      fed different methionine sources.
AB  - Methionine supplemented as 2-hydroxy-4-(methylthio)-butanoic acid (HMB) has been
      suggested to alter bacterial or protozoal populations in the rumen. Our objective
      was to determine if source of Met would change microbial populations in the rumen
      and to compare those results to samples from the omasum. The ruminal and omasal
      samples were collected from cows fed control (no Met), dl-Met, HMB, or the
      isopropyl ester of HMB (HMBi; estimated 50% rumen protection) in a replicated 4 x
      4 Latin square design. In one square, changes in protozoal populations were
      determined using microscopic counts and denaturing gradient gel electrophoresis
      (DGGE), whereas changes in bacterial populations were determined using DGGE and
      ribosomal intergenic spacer length polymorphism (RIS-LP). Neither the protozoal
      counts nor the DGGE banding patterns derived from protozoa were different among
      the dietary treatments or for ruminal vs. omasal samples. As revealed by both
      DGGE and RIS-LP, bacterial populations clustered by treatments in ruminal and
      especially in omasal samples. Using cows from both Latin squares, the flow of
      protozoal cells from the rumen was quantified by multiplying protozoal cell count
      in omasal fluid by the omasal fluid flow (using CoEDTA as a liquid flow marker)
      or was estimated by rumen pool size of cells multiplied by either the ruminal
      dilution rate of CoEDTA (after termination of CoEDTA dosing) or the passage rate
      of Yb-marked particles. Compared with the omasal fluid flow measurement (16.4 h),
      protozoal generation time was approximated much more closely using the
      particulate than the fluid passage rate from the rumen (generation times of 15.7
      and 7.5 h, respectively). There seems to be minimal selective retention of
      protozoal genera in the rumen in dairy cattle fed every 2 h. Data support the
      validity of the omasal sampling technique under our conditions.

PMID- 17235158
TI  - Ruminal degradability and intestinal digestibility of protein and amino acids in
      treated soybean meal products.
AB  - Four lactating dairy cows equipped with ruminal and duodenal cannulas were used
      to determine the impact of different methods of treating soybean meal (SBM) on
      the ruminal degradability and intestinal digestibility of crude protein and AA.
      Solvent-extracted SBM (SE), expeller SBM (EP), lignosulfonate SBM (LS), and heat
      and soyhulls SBM (HS) were incubated in the rumen in nylon bags for 48, 24, 16,
      8, 4, 2, and 0 h according to National Research Council (2001) guidelines.
      Additional samples of each SBM product were also incubated for 16 h in the rumen;
      the residues from these bags were transferred to mobile bags, soaked in pepsin
      HCl, and then used for determination of intestinal digestibility in situ or in
      vitro. Treatment of SBM (EP, LS, HS) protected the crude protein and AA from
      ruminal degradation, increasing rumen undegradable protein from 42% in SE to 68%
      in EP. Kinetic analysis of crude protein and AA degradation in the rumen revealed
      that, compared with LS and HS, EP exhibited slower rates of degradation but a
      shorter lag phase and a higher proportion of soluble protein. For all SBM
      products, the pattern of ruminal degradation, at 16 h of incubation, was
      characterized by extensive degradation of Lys and His, whereas Met and the
      branched-chain AA were degraded to the least extent. Estimates of intestinal
      digestibility of AA and crude protein were lower when measured in vitro than in
      situ; the magnitude of the difference between the 2 methods was greater (25%)
      with treated SBM products than with SE (10%). The availability of essential and
      nonessential AA was consistently greater (30%) with treated SBM than with SE.
      Among the treated SBM products, 4 essential AA (Ile, Leu, Phe, and Val) showed
      differences in availability, with values consistently lower for HS than for LS.
      This study showed that, based on in situ measures, heat and chemical treatment of
      SBM enhanced AA availability, and that compared with HS, EP and LS had a higher
      potential to enhance the AA supply to the small intestine of high-producing dairy
      cows.

PMID- 17235159
TI  - Milk from forage as affected by rumen degradable protein and corn grinding when
      feeding corn- and alfalfa silage-based diets.
AB  - To increase the production of milk from forage (MF), a previous experiment with
      alfalfa silage showed the importance of a complementary combination of
      concentrates and forages offered. When corn silage is fed with alfalfa,
      increasing the rumen degradable protein (RDP) content in the diet should allow a
      better utilization of forage energy. To evaluate this hypothesis, 8 multiparous
      Holstein cows in early lactation were used in a replicated 4 x 4 Latin square
      design with 3-wk periods. Diets were fed as total mixed rations and were
      formulated to provide similar levels of net energy for lactation and crude
      protein but differing in RDP. Corn and alfalfa silages were used. Treatments
      were: 1) cracked corn-based concentrate providing low RDP [level recommended by
      the NRC (2001); RDP = 11.1% of dry matter (DM)]; 2) cracked corn-based
      concentrate providing medium RDP (RDP = 12.8% of DM); 3) cracked corn-based
      concentrate providing high RDP (RDP = 14.5% of DM); and 4) ground corn-based
      concentrate providing high RDP (RDP = 13.6% of DM). The first 3 treatments, using
      cracked corn, were compared on the basis of their RDP level. For these
      treatments, MF, calculated on a protein basis, decreased and the average of MF
      calculated on an energy basis and MF calculated on a protein basis tended to
      decrease as RDP increased. There was no difference for MF calculated on an energy
      basis between treatments. Increasing dietary RDP levels decreased the milk yield
      (from 32.8 to 30.7 kg/d) and milk protein yield (from 1,094 to 1,005 g/d) but not
      the milk fat yield. The milk urea N concentration increased as RDP increased.
      This suggests that there is no advantage of feeding RDP above the NRC
      recommendations when diets are based on corn and alfalfa silage. At high RDP
      levels (treatments 3 and 4), ground corn supported higher DM intake and yields of
      milk and protein than did cracked corn. Milk from forage, calculated on a protein
      basis, was higher and milk urea N decreased with ground corn. Even with corn
      silage in the diet, grinding corn grain proved to be beneficial to milk yield and
      MF production.

PMID- 17235160
TI  - Effect of heat and high-pressure treatments on microbiological quality and
      immunoglobulin G stability of caprine colostrum.
AB  - Caprine colostrums (6 batches) were subjected to heat (56 degrees C for 60 min
      and 63 degrees C for 30 min) and high-pressure (400 and 500 MPa for 10 min at 20
      degrees C) treatments at laboratory scale, and analyses of the main microbial
      groups and the extent of IgG denaturation (determined by immunodiffusion) were
      performed. Overall mean microbial values in raw colostrums were: total count,
      5.55 log cfu/mL; Enterobacteriaceae, 2.64 log cfu/mL; lactococci, 5.41 log
      cfu/mL; lactobacilli, 2.34 log cfu/mL; and enterococci, 4.06 log cfu/mL. Neither
      Salmonella spp. nor Listeria monocytogenes were detected, whereas coagulase
      positive staphylococci were found in various colostrum samples with an overall
      mean of 1.02 log cfu/mL. Heat and high-pressure treatments significantly reduced
      total count (1.47 log), lactococci (1.45 log), enterococci (2.47 log), and
      Enterobacteriaceae, whereas lactobacilli and coagulase-positive staphylococci
      counts were reduced to undetectable levels, but differences between technological
      treatments were not statistically significant. High-pressure treatments were as
      efficient in reducing the bacterial population as were heat pasteurization
      treatments: 95.50 and 96.93% for pressure treatments of 400 and 500 MPa, and
      91.61 and 97.59% for heat treatments of 56 degrees C for 60 min and 63 degrees C
      for 30 min, respectively. All treatments assayed produced a reduction in
      colostrum IgG concentration (27.53, 23.58, 23.33, 22.09, and 17.06 mg/mL for raw,
      heat-treated at 56 degrees C for 60 min or 63 degrees C for 30 min, and pressure
      treated at 400 and 500 MPa, respectively), but differences were only observed
      between raw colostrums and those pressure-treated at 500 MPa. This laboratory
      scale study indicated that 20- to 30-mL volumes of goat colostrum could be heated
      and pressure-treated (400 MPa) to produce hygienic colostrum without affecting
      IgG concentration.

PMID- 17235161
TI  - Development of a mechanistic model to represent the dynamics of liquid flow out
      of the rumen and to predict the rate of passage of liquid in dairy cattle.
AB  - A mechanistic and dynamic model was developed to represent the physiological
      aspects of liquid dynamics in the rumen and to quantitatively predict liquid flow
      out of the reticulorumen (RR). The model is composed of 2 inflows (water
      consumption and salivary secretion), one outflow (liquid flow through the
      reticulo-omasal orifice (ROO), and one in-and-out flow (liquid flux through the
      rumen wall). We assumed that liquid flow through the ROO was coordinated with the
      primary reticular contraction, which is characterized by its frequency, duration,
      and amplitude during eating, ruminating, and resting. A database was developed to
      predict each component of the model. A random coefficients model was used with
      studies as a random variable to identify significant variables. Parameters were
      estimated using the same procedure only if a random study effect was significant.
      The input variables for the model were dry matter intake, body weight, dietary
      dry matter, concentrate content in the diet, time spent eating, and time spent
      ruminating. Total water consumption (kg/d) was estimated as 4.893 x dry matter
      intake (kg/d), and 20% of the water consumed by drinking was assumed to bypass
      the RR. The salivary secretion rate was estimated to be 210 g/min during chewing.
      During ruminating, however, the salivation rate was assumed to be adjusted for
      the proportion of liquid in the rumen. Resting salivation was exponentially
      related to dry matter intake. Liquid efflux through the rumen wall was assumed to
      be the mean value in the database (4.6 kg/h). The liquid outflow rate (kg/h) was
      assumed to be a product of the frequency of the ROO opening, its duration per
      opening, and the amount of liquid passed per opening. Simulations of our model
      suggest that the ROO may open longer for each contraction cycle than had been
      previously reported (about 3 s) and that it is affected by dry matter intake,
      body weight, and total digesta in the rumen. When compared with 28 observations
      in 7 experiments, the model accounted for 40, 70, and 90% of the variation, with
      root mean square prediction errors of 9.25 kg, 1.84 kg/h, and 0.013 h(-1) for
      liquid content in the rumen, liquid outflow rate, and fractional rate of liquid
      passage, respectively. A sensitivity analysis showed that dry matter intake,
      followed by body weight and time spent eating, were the most important input
      variables for predicting the dynamics of liquid flow from the rumen. We conclude
      that this model can be used to understand the factors that affect the dynamics of
      liquid flow out of the rumen and to predict the fractional rate of liquid passage
      from the RR in dairy cattle.

PMID- 17235162
TI  - Ruminal lipopolysaccharide concentration and inflammatory response during grain
      induced subacute ruminal acidosis in dairy cows.
AB  - The effects of grain-induced subacute ruminal acidosis (SARA) in lactating dairy
      cows on free ruminal lipopolysaccharide (LPS) and indicators of inflammation were
      determined. Four mid lactation dairy cows were divided into 2 groups of 2 cows
      and used in a repeated switchover design. During each period, SARA was induced in
      2 animals for 5 subsequent days by replacing 25% of their total mixed ration (dry
      matter basis) with a concentrate made of 50% wheat and 50% barley. The other 2
      cows acted as controls and were fed a total mixed ration diet in which 44% of dry
      matter was concentrate. On average, inducing SARA did not affect milk
      composition, increased the duration of rumen pH below 5.6 from 187 to 309 min/d,
      and increased free ruminal LPS concentration from 24,547 endotoxin units (EU)/mL
      to 128,825 EU/mL. Averaged across treatments, milk fat yield and milk protein
      yield were 0.66 and 1.00 kg/d, respectively. Rumen pH and milk fat data suggest
      that control cows also experienced ruminal acidosis, albeit a milder form of this
      disease than SARA cows. Serum LPS concentration in both control and SARA cows was
      less than the detection limit of <0.01 EU/mL for the assay. Induction of SARA
      elevated serum amyloid A concentration from 286.8 to 498.8 mug/mL, but did not
      affect other markers of inflammation including haptoglobin, fibrinogen, serum
      copper, or white blood cells. These results suggest that grain-induced SARA in
      mid lactation dairy cows increases the lysis of gram-negative bacteria and
      activates an inflammatory response.

PMID- 17235163
TI  - Measurement of milk intake in suckling llamas (Lama glama) using deuterium oxide
      dilution.
AB  - The objective of the study was to estimate daily milk intake in llama crias and
      relate nutrient intakes at peak lactation to growth data. Milk intake in 11
      suckling llamas was estimated from water kinetics using deuterium oxide (D2O) at
      d 17, 66, and 128 postpartum. Daily milk intakes averaged 2.6, 2.3, and 2.0 kg at
      17, 66, and 128 d postpartum, respectively. Milk intake decreased with age when
      expressed as daily amount, percentage of body weight (BW), or per kilogram of
      metabolic size, but the influence of age was eliminated when expressed per gram
      of daily gain. Because llamas only have one young per parturition, milk intake
      was equivalent to the daily milk output of the dam, which ranged from 27.6 to
      96.9 g/kg of maternal BW(0.75). Compared with different ruminant species, milk
      production in llamas appears to lie between wild and domestic ruminants used for
      meat production. Nutrients (dry matter, fat, protein, and lactose) and energy
      intakes from the milk calculated by combining milk intake and milk composition
      data decreased with age when expressed as daily amount or per 100 g of BW, but
      when expressed per gram of daily gain, no clear trend was observed. Maintenance
      requirement for suckling llamas at peak lactation (17 d postpartum) was 312 kJ of
      ME/kg of BW(0.83). Combined with milk composition data, the present milk intake
      estimations at different stages of the lactation can be used to establish
      recommendations for nutrient and energy requirements of suckling llamas.

PMID- 17235164
TI  - Pre- and postweaning performance of holstein female calves fed milk through step
      down and conventional methods.
AB  - Milk consumption, dry feed intake, body weight (BW) gain, occurrence of diarrhea,
      and selected blood metabolites were studied in female Holstein calves fed milk
      either through conventional or step-down (STEP) methods. In conventional method,
      the calves (n = 20) were fed colostrum and then milk at the rate of 10% of BW for
      the entire period of 45 d. In STEP method, the calves (n = 20) were given
      colostrum and then milk for 25 d at the rate of 20% of BW, which was reduced
      (between d 26 to 30) to 10% of BW for the remaining 15 d. The calves fed through
      conventional and STEP methods were weaned gradually by diluting milk with water
      between d 46 and 50. Feed intake and BW of the calves were monitored until 90 d
      of age. The STEP calves consumed 92.3, 19.4, and 62.4% more milk than
      conventionally fed calves during pre-STEP (d 1 to 30), post-STEP (d 31 to 50),
      and preweaning (d 1 to 50) periods, respectively. Consumption of starter and hay
      were greater during the pre-STEP period and lesser during the post-STEP and
      postweaning (d 51 to 90) periods in calves provided milk using conventional
      method compared with STEP-fed calves. Body weight gain, dry matter intake, and
      feed efficiency of calves were greater in those on the STEP method than on the
      conventional method. Lesser blood glucose and greater blood urea nitrogen at
      weaning (d 50) and postweaning (d 60) possibly indicated a better functioning
      rumen in calves fed milk through The STEP method than those fed conventionally.
      Occurrence of diarrhea was higher during wk 3 and 4 of age in calves fed milk
      through conventional method compared with STEP-fed calves. In conclusion, STEP
      milk feeding may prevent the problems of depressed solid feed intake associated
      with ad libitum milk feeding and of poor BW gain with conventional milk feeding
      in dairy calves.

PMID- 17235166
TI  - Effects of two different feeding strategies during dry-off on certain health
      aspects of dairy cows.
AB  - With increasing milk production and short calving intervals, high daily milk
      yields at dry-off are rather common, making the dry-off procedure difficult and
      increasing the risk for health problems during the dry-off period. The objective
      of the following study was to compare the effects of 2 dry-off protocols, using
      different nutrient supplies, on health, as measured by clinical findings,
      intramammary infections, milk somatic cell count, and plasma concentrations of
      cortisol, serum amyloid A, haptoglobin, and Mg, in dairy cows. Twenty-one primi-
      and multiparous dairy cows were randomly assigned to 2 different feeding
      treatments. One group was fed ad libitum straw (straw), whereas the other group
      was fed 4 kg of DM silage daily and ad libitum straw (silage) during dry-off
      (i.e., for 5 d). All cows were milked in the morning of d 3 and 5 during this
      period. At the start of dry-off (d 0), the average daily milk yield was 17.1 +/-
      0.8 kg. The plasma cortisol concentration increased during dry-off only in cows
      fed straw. There was no significant effect of treatment on plasma serum amyloid
      A, but the concentration increased during dry-off in both groups. The plasma Mg
      concentration decreased during dry-off, and the values tended to be lower in the
      straw group. The milk somatic cell count increased in both groups during dry-off
      but did not differ between groups. In both groups the heart rate decreased at dry
      off, but the decrease was more pronounced in the straw group. Overall, this study
      (together with a previous report) shows that the common dry-off procedure of
      feeding straw only may give rise to metabolic disturbances. However, this might
      be avoided without any apparent negative effects on udder health if a limited
      amount of silage is added during dry-off.

PMID- 17235165
TI  - Effects of essential oils on digestion, ruminal fermentation, rumen microbial
      populations, milk production, and milk composition in dairy cows fed alfalfa
      silage or corn silage.
AB  - Four Holstein cows fitted with ruminal cannulas were used in a 4 x 4 Latin square
      design (28-d periods) with a 2 x 2 factorial arrangement of treatments to
      investigate the effects of addition of a specific mixture of essential oil
      compounds (MEO; 0 vs. 750 mg/d) and silage source [alfalfa silage (AS) vs. corn
      silage (CS)] on digestion, ruminal fermentation, rumen microbial populations,
      milk production, and milk composition. Total mixed rations containing either AS
      or CS as the sole forage source were balanced to be isocaloric and
      isonitrogenous. In general, no interactions between MEO addition and silage
      source were observed. Except for ruminal pH and milk lactose content, which were
      increased by MEO supplementation, no changes attributable to the administration
      of MEO were observed for feed intake, nutrient digestibility, end-products of
      ruminal fermentation, microbial counts, and milk performance. Dry matter intake
      and milk production were not affected by replacing AS with CS in the diet.
      However, cows fed CS-based diets produced milk with lower fat and higher protein
      and urea N concentrations than cows fed AS-based diets. Replacing AS with CS
      increased the concentration of NH(3)-N and reduced the acetate-to-propionate
      ratio in ruminal fluid. Total viable bacteria, cellulolytic bacteria, and
      protozoa were not influenced by MEO supplementation, but the total viable
      bacteria count was higher with CS- than with AS-based diets. The apparent
      digestibility of crude protein did not differ between the AS and CS treatments,
      but digestibilities of neutral detergent fiber and acid detergent fiber were
      lower when cows were fed CS-based diets than when they were fed AS-based diets.
      Duodenal bacterial N flow, estimated using urinary purine derivatives and the
      amount of N retained, increased in cows fed CS-based diets compared with those
      fed AS-based diets. Feeding cows AS increased the milk fat contents of cis-9,
      trans-11 18:2 (conjugated linoleic acid) and 18:3 (n-3 fatty acid) compared with
      feeding cows CS. Results from this study showed limited effects of MEO
      supplementation on nutrient utilization, ruminal fermentation, and milk
      performance when cows were fed diets containing either AS or CS as the sole
      forage source.

PMID- 17235167
TI  - Comparative evaluation of alternative forages to grass silage in the diet of
      early lactation dairy cows.
AB  - Fifty-six autumn-calving Holstein-Friesian cows, blocked on the basis of days in
      milk (27.6 +/- 10.65 d), lactation number (3.1 +/- 2.21), and preexperimental
      milk yield (28.4 +/- 6.69 kg) were used to examine the effects of replacing 330
      g/kg of dry matter (DM) of first-cut perennial ryegrass silage with either
      fermented whole-crop wheat (WCW), urea-treated processed WCW, or corn silage on
      subsequent feed intake, milk production, and efficiency of nitrogen utilization.
      The DM (g/kg), crude protein (CP, g/kg of DM) and in vitro DM digestibility
      (g/kg) of the forages were 204, 179, and 762 for grass silage; 389, 90, and 711
      for fermented WCW; 795, 141, and 768 for urea-treated processed WCW; and 346, 93,
      and 783 for corn silage, respectively. Four forage treatments were evaluated as
      follows: 1) grass silage as the sole forage (GS); 2) a mixture of grass silage
      and fermented WCW silage, (F-WCW); 3) a mixture of grass silage and urea-treated
      processed WCW, (UP-WCW); and 4) a mixture of grass silage and corn silage (CS).
      In all cases, the alternative forages comprised 67% of the forage mix on a DM
      basis. Isonitrogenous diets were formulated by offering all cows 8 kg of
      concentrate as fed, formulated to different CP concentrations. Cows were offered
      these diets from 28 to 104 d in milk. Total DM intake and milk yield were greater
      on UP-WCW (20.0 and 30.2 kg/d) and CS (18.3 and 33.2 kg/d) than on GS (13.5 and
      26.5 kg/d). Although DM intake was greater on F-WCW (17.1 kg/d) than on GS, milk
      yield was not significantly greater (+2.7 kg/d). Milk protein concentration was
      greater on F-WCW (30.5 g/kg), UP-WCW (31.3 g/kg), and CS (30.7 g/kg) than on GS
      (28.5 g/kg). However, there was no difference between treatments in milk fat or
      lactose concentrations. Body weight change was greater for cows offered GS (-0.27
      kg/d) than for those offered UP-WCW (-0.01 kg/d) and CS (+0.05 kg/d) but not
      compared with those offered F-WCW (-0.06 kg/d). There was no effect of treatment
      on plasma glucose, nonesterified fatty acids, beta-hydroxybutyrate, urea, or
      total protein at d 64 +/- 17.4 and d 92 +/- 17.4 postpartum. Efficiency of N
      utilization was greatest for CS with 0.36 of N intake being recovered in milk
      compared with 0.28, 0.32, and 0.26 for GS, F-WCW, and UP-WCW, respectively. There
      was no effect of treatment on milk urea N concentration or the urinary allantoin
      N to creatinine N ratio. The results of this experiment indicate that corn silage
      is a more suitable supplementary forage to grass silage than fermented or urea
      treated processed WCW, with advantages realized in milk production and more
      efficient N utilization.

PMID- 17235168
TI  - Occurrence of selenoprotein enzyme activities and mRNA in bovine mammary tissue.
AB  - To elucidate the possible role of selenoproteins for milk formation and mammary
      gland physiology, the activities of selenoprotein enzymes and the expression of
      selenoprotein genes were studied in the bovine mammary gland. Messenger RNA was
      demonstrated for selenoprotein P, thioredoxin reductase 1, and for glutathione
      peroxidase (GPx) 1, 3, and 4. Significant differences in mRNA expression between
      the cows were seen for GPx 1 and GPx 3. The enzyme activity of glutathione
      peroxidase varied approximately 16-fold among cows, and the activity of
      thioredoxin reductase and the concentration of soluble Se varied approximately 6
      fold among cows. There were positive correlations between glutathione peroxidase
      activity, thioredoxin reductase activity, and soluble Se, the correlation between
      glutathione peroxidase activity and soluble Se being the strongest. Furthermore,
      selenoprotein P expression correlated with GPx 1 mRNA expression and with soluble
      Se. There was also a correlation between glutathione peroxidase activity and the
      mRNA expression of GPx 1. The general conclusion from the data was that the
      activity of glutathione peroxidase and thioredoxin reductase and the mRNA
      expression of selenoprotein P and GPx 1 and 3 were influenced by Se status, but
      the expression of GPx 4 and thioredoxin reductase 1 were not. These results
      indicate that the Se status in mammary tissue is an important regulator of
      selenoprotein activity and expression, but that other factors are also in
      operation.

PMID- 17235169
TI  - Concentrations of butyric acid bacteria spores in silage and relationships with
      aerobic deterioration.
AB  - Germination and growth of spores of butyric acid bacteria (BAB) may cause severe
      defects in semihard cheeses. Silage is the main source of BAB spores in cheese
      milk. The objectives of the study were to determine the significance of grass
      silages and corn silages as sources of BAB spores and to investigate the
      relationships between high concentrations of BAB spores in corn silage and
      aerobic deterioration. In the first survey, samples were taken from various
      locations in silos containing grass and corn silages and from mixed silages in
      the ration offered to the cows on 21 farms. We demonstrated that the quantity of
      BAB spores consumed by cows was determined by a small fraction of silage with a
      high concentration of spores (above 5 log10 BAB/g). High concentrations were most
      often found in corn silage within areas with visible molds (69% of the samples).
      Areas with visible molds in grass silage and surface layers of corn silage
      contained, respectively, 21 and 19% of the cases of concentrations above 5 log10
      BAB spores/g. Based on these results, we concluded that currently in the
      Netherlands, corn silage is a more important source of BAB than is grass silage.
      In a second survey, 8 corn silages were divided into 16 sections and each section
      was studied in detail. High concentrations of BAB spores were found in only the
      top 50 cm of these 8 silages. Elevated concentrations of BAB spores were
      associated with different signs of aerobic deterioration. In 13% of the sections
      in corn silage with more than 5 log10 yeasts and molds/g, more than 5 log10 BAB
      spores/g were found. Sections with a temperature of more than 5 degrees C above
      ambient temperature contained, in 21% of the cases, more than 5 log10 BAB
      spores/g. Concentrations above 5 log10 BAB spores/g were measured in 50% of the
      sections with a pH above 4.4. All sections with a pH above 4.4 also showed a
      temperature that was more than 5 degrees C above ambient temperature and a
      concentration of yeasts and molds above 5 log10 cfu/g. Based on these results, we
      postulated that high concentrations of BAB spores in corn silage are the result
      of oxygen penetration into the silage, resulting in aerobic deterioration and the
      formation of anaerobic niches with an increased pH just below the surface. Growth
      of BAB in these anaerobic niches with an increased pH caused the locally high
      concentrations of BAB in corn silage.

PMID- 17235170
TI  - Effects of prepartum administration of a monensin controlled release capsule on
      rumen pH, feed intake, and milk production of transition dairy cows.
AB  - Effects of prepartum administration of a monensin controlled release capsule
      (CRC) on rumen pH, dry matter intake, and milk production during the transition
      period and early lactation were determined in 16 multiparous Holstein cows. Cows
      were divided into blocks of 2 depending on calving date. Cows were fed either a
      close-up dry cow or a lactating cow total mixed ration ad libitum. Rumen pH was
      monitored continuously using indwelling probes. Monensin did not affect average
      daily rumen pH, time below pH 6, time below pH 5.6, area below pH 6, and area
      below pH 5.6 throughout the experiment. Average daily pH, time below pH 6, and
      time below pH 5.6 before calving were 6.62, 65.6 min/d, and 17.6 min/d,
      respectively, and did not differ among the weeks before calving. Average daily
      pH, time below pH 6, and time below pH 5.6 were 6.19, 443.3 min/d, and 115.5
      min/d, respectively, during the first week after calving, and were 6.36, 204.3
      min/d, and 52.4 min/d, respectively, during the sixth week after calving. In the
      weeks after calving, average daily pH showed a quadratic increase, time below pH
      6 showed a quadratic decrease, and time below pH 5.6 showed a linear decrease.
      Monensin did not affect dry matter intake and daily yields of milk, milk fat, and
      milk protein. Results suggest that prepartum administration of a monensin CRC did
      not increase rumen pH in multiparous cows fed the experimental diets during the
      transition period and early lactation.

PMID- 17235171
TI  - Limit feeding of gravid Holstein heifers: effect on growth, manure nutrient
      excretion, and subsequent early lactation performance.
AB  - A study was conducted to evaluate the effect of limit feeding on growth, feed
      efficiency, and manure excretion in Holstein heifers and subsequent milk
      production. Fifty-four gravid Holstein heifers were randomly assigned to
      replicate pens and fed 1 of 3 experimental diets for 111 d. Experimental diets
      included an ad libitum-fed control diet containing 11.3% crude protein (CP) and
      2.46 Mcal/kg of metabolizable energy (ME). Two limit-fed diets of increased
      nutrient density were formulated to contain 12.7 and 14.2% CP and 2.55 and 2.68
      Mcal/kg of ME, respectively. Feed intakes of limit-fed diets were limited to 90
      and 80% of the control diet. Nutrient intake, growth, manure excretion, blood
      metabolites, behavior, and 150-d lactation performance were evaluated. Heifers
      fed 80 and 90% of the control diet consumed less dry matter (8.3 and 9.0 vs. 9.7
      kg/d), but similar amounts of net energy for gain (9.5 and 9.4 vs. 9.4 Mcal/d)
      and CP (1.17, 1.15 vs. 1.10 kg/d) as compared with control diet-fed heifers. The
      weight gain and skeletal growth of heifers were not different, but heifers limit
      fed at 80 and 90% of the control had improved feed efficiency. Heifers limit fed
      at 80 and 90% of ad libitum intake excreted 0.86 and 0.36 kg/d less dry matter,
      respectively, as compared with control diet-fed heifers, but all heifers excreted
      similar amounts of N and P. Limit feeding did not affect calf birth weight,
      dystocia, or lactation performance. Limit feeding gravid heifers improved feed
      efficiency and reduced manure dry matter excretion without negative effects on
      lactation performance.

PMID- 17235172
TI  - Isolation of bovine immunoglobulins resistant to peptic digestion: new
      perspectives in the prevention of failure in passive immunization of neonatal
      calves.
AB  - In calves, neonatal mortality and disease susceptibility are greatly influenced
      by failure in passive immunization, normally provided by colostrum ingestion just
      after birth. Formulations projected to replace natural colostrum have not been
      successful, and one of the possible reasons for such failure is that orally
      administered Ig are probably digested in the gastrointestinal tract, so they are
      not absorbed as intact functional molecules. With the aim of finding an adequate
      colostrum substitute, we used columns of immobilized jacalin, a lectin known by
      its ability to bind O-linked oligosaccharides, to obtain a colostral Ig
      population putatively protected against enzymatic cleavage by the presence of
      sugar chains. Immunoglobulin G1 is a major constituent of colostrum Ig bound to
      jacalin (JB-Ig). This preparation contains 10% of the total colostral Ig and is
      typically 3 to 6 times more resistant to pepsin digestion than the Ig contained
      in the fraction that is not bound to jacalin, which presumably does not contain O
      glycans. Mass spectrometry analysis demonstrated that the tryptic peptides
      obtained from JB-Ig and unbound Ig were similar, indicating that their distinct
      susceptibility to enzyme hydrolysis was associated with differences in their
      sugar chains. Therefore, the present research suggests that the bovine colostrum
      JB-Ig has potential application in the immunotherapy of neonatal calves that have
      not been supplied with colostrum.

PMID- 17235173
TI  - The effect of solids dilution rate and oil source on trans C18:1 and conjugated
      linoleic acid production by ruminal microbes in continuous culture.
AB  - The objective of this study was to evaluate the effect of solids dilution rate
      (SDR) and oil source [soybean oil (SBO) or linseed oil (LSO)] on the ruminal
      production of trans C18:1 and conjugated linoleic acid (CLA). A dual-flow
      continuous culture system consisting of 4 fermenters was used in a 4 x 4 Latin
      square design with a factorial arrangement of treatments over 4 consecutive
      periods of 10 d each. Treatment diets (50:50 forage to concentrate) were fed at
      120 g/d of dry matter (DM) in 3 equal portions. The concentrate mix contained 1%
      fish oil and either 2% SBO or 2% LSO on a DM basis. Treatments were as follows:
      1) SBO at 6%/h SDR, 2) SBO at 3%/h SDR, 3) LSO at 6%/h SDR, and 4) LSO at 3%/h
      SDR. The oil source by SDR interaction was not significant for trans C18:1 and
      CLA fatty acids. The concentrations of trans C18:1 and vaccenic acid were greater
      in effluents when diets were supplemented with SBO vs. LSO (37.11 vs. 34.09 and
      32.71 vs. 29.70 mg/g of DM, respectively) and at high SDR than low SDR (37.60 vs.
      33.61 and 32.72 vs. 29.61 mg/g of DM, respectively). The concentration of cis-9,
      trans-11 CLA in effluents was also greater with SBO than LSO (0.81 vs. 0.40 mg/g
      of DM) supplementation and at high SDR than low SDR (0.68 vs. 0.54 mg/g of DM).
      Biohydrogenation of linoleic acid and linolenic acid increased at higher SDR
      within each oil treatment. Based on these results, SBO supplementation at high
      SDR enhances ruminal production of vaccenic acid, and therefore could potentially
      enhance cis-9, trans-11 CLA in milk fat through synthesis by Delta9-desaturase.

PMID- 17235175
TI  - Manipulation of soluble and rumen-undegradable protein in diets fed to
      postpubertal dairy heifers.
AB  - Eight postpubertal Holstein heifers (455 +/- 4.0), fit with rumen cannulas, were
      used in 2 experiments to investigate the effects of altering dietary protein type
      on nutrient digestibility, rumen fermentation, and nitrogen utilization. Heifers
      were fed diets containing low or high levels of soluble (SP) and low or high
      levels of rumen-undegradable protein (RUP) in a 4 x 4 Latin square design with a
      2 x 2 factorial arrangement of treatments. The treatment rations in experiment 1
      were formulated with corn silage composing the majority of the forage fraction,
      whereas in experiment 2, grass hay composed the highest proportion of ration DM.
      Blood and rumen samples were collected over 2 d and total fecal and urine
      collections were conducted for 4 d. Dry matter, organic matter, and neutral
      detergent fiber digestibility were not different in either experiment 1 or 2.
      Increasing the proportion of dietary crude protein that was SP increased mean
      daily rumen ammonia concentrations in each experiment, although no other rumen
      parameter differed. Excretion of urinary nitrogen in experiment 1 was highest for
      diets with low SP and low RUP and with high SP and high RUP, which resulted in
      these rations being the least efficient in retention of apparently digested
      nitrogen. The proportion of consumed or absorbed nitrogen retained in experiment
      2 was not significantly different between treatments. Responses to alterations in
      crude protein degradability are observable in postpubertal heifers; however, the
      level of response may depend on the diet in which protein degradability is
      altered.

PMID- 17235174
TI  - Effects of dietary cation-anion difference and potassium to sodium ratio on
      lactating dairy cows in hot weather.
AB  - Forty-two lactating Holstein cows 188 +/- 59 d in milk were used in an 8-wk
      randomized complete block trial with a 2 x 3 factorial arrangement of treatments.
      The objective was to determine the effects of high dietary cation-anion
      difference (DCAD) and K:Na ratio on milk yield and composition and blood acid
      base chemistry. Treatments included DCAD concentrations of 45 or 60 mEq (Na + K 
      Cl)/100 g of feed dry matter and K:Na ratios of 2:1, 3:1, or 4:1. Mean DCAD
      values were later determined to be 41 and 58. Dry matter intake was similar
      across treatments. Yield of milk and energy corrected milk were lower for the 3:1
      K:Na ratio compared with 2:1 and 4:1 ratios. Blood urea N was lower for the
      highest DCAD, suggesting that DCAD possibly reduced protein degradation or
      altered protein metabolism and retention. Mean temperature-humidity index was
      75.6 for the duration of the trial, exceeding the critical value of 72 for all
      weeks during the treatment period. Cows maintained relatively normal body
      temperature with mean a.m. and p.m. body temperature of 38.5 and 38.7 degrees C,
      respectively. These body temperatures suggest that cows were not subject to
      extreme heat stress due to good environmental control. Results of this trial
      indicate that the greatest effect on milk yield occurs when either Na or K is
      primarily used to increase DCAD, with the lowest yield of energy-corrected milk
      at a 3:1 K:Na ratio (27.1 kg/d) compared with ratios of 2:1 (29.3 kg/d) and 4:1
      (28.7 kg/d). Results also suggest that greater DCAD improves ruminal N metabolism
      or N utilization may be more efficient with a high DCAD.

PMID- 17235177
TI  - Short communication: Identification of diseased calves by use of data from
      automatic milk feeders.
AB  - Housing calves in large groups is associated with a higher risk of respiratory
      disease and with increased difficulties in identifying diseased animals compared
      with single housing. The aim of the present study was to investigate the effect
      of clinical disease on some behaviors recorded by automatic milk feeders in pre
      weaned dairy calves. The experiment included 27 calves from a Danish research
      farm and 41 calves from a Swedish research farm. The calves were fed
      restrictively from a computer-controlled milk feeder, and all calves were
      subjected to daily clinical examinations for 3 to 26 d, with information gathered
      on general condition, nasal discharge, lung auscultation findings, coughing,
      signs of dehydration, naval status, rectal temperature, fecal consistency, and
      presence of chin abscess, arthritis, umbilical hernia, poor body condition, and
      poor hair coat. Calves suffering from diarrhea, respiratory disease, fever, or
      unspecific decreased general condition for more than 2 d were considered to be
      diseased and were declared to have recovered when they had been free of clinical
      signs of the disease for at least 2 d. The effects of clinical status (healthy,
      diseased) on the number of rewarded and unrewarded visits to the calf feeder and
      drinking rate, respectively, were analyzed by variance component analysis using a
      mixed model. Milk consumption on diseased and nondiseased days within calves was
      compared using a Wilcoxon signed rank test. In total, 53 of the calves were
      diagnosed as diseased during the study period. All cases of diseases were mild
      and were associated with an unaffected or only mildly affected general condition.
      Diarrhea was diagnosed in 51 calves, 6 of which also had respiratory disease. In
      2 calves, respiratory disease was the only diagnosis. Eleven calves had an
      unspecific decreased general condition. The number of unrewarded visits was
      significantly reduced when calves were diseased. In Swedish calves, there was
      also a tendency for rewarded visits to be reduced during diseased days. Drinking
      rate and number of rewarded visits increased with increasing age. No effect of
      clinical status on milk consumption was detected. The number of unrewarded visits
      was the most sensitive of the 4 feeding behaviors monitored to indicate clinical
      disease in calves fed restricted milk volumes.

PMID- 17235176
TI  - Effect of varying levels of fatty acids from palm oil on feed intake and milk
      production in Holstein cows.
AB  - To determine the optimum feeding level of fatty acids of palm oil (PALM;
      Energizer RP10; 86.6% palmitic acid) on milk production, lactating cows (n = 18)
      were randomly assigned to a treatment sequence in replicated 4 x 4 Latin squares.
      Animals were assigned to squares by parity (3 multiparous and 1 primiparous
      squares with primiparous in the incomplete square). The 4 diets were designed to
      provide 0, 500, 1,000, and 1,500 g of PALM per day. Cows were fed individually
      with feed intake measured daily. Each period lasted 16 d with milk production and
      composition determined the final 2 d. Milk production, milk composition and feed
      intake data were analyzed using the MIXED procedure of SAS. Milk yields were
      30.9, 34.0, 34.2, and 34.2 kg/ d (SEM = 1.9) for the 0, 500, 1,000, and 1,500 g
      levels, respectively. Milk yield was increased by the addition of PALM; however,
      there were no differences among the levels of PALM. Milk fat percentage was also
      increased from 3.44% for 0 g to 3.95% (SEM = 0.17) across all levels of PALM but
      there were no differences among the PALM treatments. Dry matter intakes were
      23.3, 26.4, 24.7, and 23.8 kg/d (SEM = 1.4) for the 0, 500, 1,000 and 1,500 g
      levels, respectively. The addition of PALM increased milk yield and milk fat
      percentage, and no adverse effects on dry matter intake were observed.

PMID- 17235178
TI  - Effectiveness of oils rich in linoleic and linolenic acids to enhance conjugated
      linoleic acid in milk from dairy cows.
AB  - Forty Holstein dairy cows were used to determine the effectiveness of linoleic or
      linolenic-rich oils to enhance C18:2 cis-9, trans-11 conjugated linoleic acid
      (CLA) and C18:1 trans-11 (vaccenic acid; VA) in milk. The experimental design was
      a complete randomized design for 9 wk with measurements made during the last 6
      wk. Cows were fed a basal diet containing 59% forage (control) or a basal diet
      supplemented with either 4% soybean oil (SO), 4% flaxseed oil (FO), or 2% soybean
      oil plus 2% flaxseed oil (SFO) on a dry matter basis. Total fatty acids in the
      diet were 3.27, 7.47, 7.61, and 7.50 g/100 g in control, SO, FO, and SFO diets,
      respectively. Feed intake, energy-corrected milk (ECM) yield, and ECM produced/kg
      of feed intake were similar among treatments. The proportions of VA were
      increased by 318, 105, and 206% in milk fat from cows in the SO, FO, and SFO
      groups compared with cows in the control group. Similar increases in C18:2 cis-9,
      trans-11 CLA were 273, 150, and 183% in SO, FO, and SFO treatments, respectively.
      Under similar feeding conditions, oils rich in linoleic acid (soybean oil) were
      more effective in enhancing VA and C18:2 cis-9, trans-11 CLA in milk fat than
      oils containing linolenic acid (flaxseed oil) in dairy cows fed high-forage diets
      (59% forage). The effects of mixing linoleic and linolenic acids (50:50) on
      enhancing VA and C18:2 cis-9, trans-11 CLA were additive, but not greater than
      when fed separately. Increasing the proportion of healthy fatty acids (VA and
      CLA) by feeding soybean or flaxseed oil would result in milk with higher
      nutritive and therapeutic value.

PMID- 17235179
TI  - Selection on yield and fitness traits when culling holsteins during the first
      three lactations.
AB  - Emphasis by dairy producers on various yield and fitness traits when culling cows
      was documented for US Holstein calvings since 1982. Least squares differences
      between cows retained for additional parities and those culled were estimated for
      milk, fat, and protein yields; somatic cell score (SCS); days open (DO); dystocia
      score (DS), final score (FS), and 14 type traits. Compared with cows culled
      during first lactation, superiority for first-parity milk yield was 569 to 1,175
      kg for cows with 2 lactations, 642 to 1,283 kg for cows with > or =2 lactations,
      710 to 1,350 kg for cows with 3 lactations, and 663 to 1,331 kg for cows with >
      or =4 lactations. Cows retained for > or =2 lactations had first-parity SCS that
      were 0.34 to 0.62 lower (more favorable) than those of cows culled during first
      lactation; first-parity SCS for cows retained for 3 or > or =4 lactations were
      even more favorable than those of cows with 1 or 2 lactations. The negative
      genetic relationship between yield and fertility contributed to increased DO as
      selection for higher milk yield persisted across time despite considerable
      preference for early conception when culling cows. In 1982, cows retained in the
      herd for 2, 3, and > or =4 lactations conceived earlier during first lactation
      (19, 17, and 23 fewer DO, respectively) than those culled during first lactation;
      those differences had increased to 34, 41, and 52 fewer DO by 2000. Although DS
      has a negative relationship with survival, first-parity DS were only slightly
      lower (by 0.10 to 0.14) for survivors than for cows culled during first
      lactation. Cows retained for > or =2 lactations had greater first-parity FS by
      1.4 to 1.9 points than those culled during first lactation. On a standardized
      basis, the most intense selection during first lactation was for milk and protein
      yields with less for fat (74 to 86% of that for milk), DO (18 to 74%), FS (22 to
      38%), SCS (19 to 37%), and DS (7 to 15%). Producers continued to emphasize the
      same traits when culling during second and third lactations. Trait priority by
      producers during culling could aid in setting trait emphasis when selecting bulls
      for progeny test and could also be useful in developing software for index-based
      culling guides.

PMID- 17235180
TI  - Short communication: Genetic evaluation of milking speed for Brown Swiss dairy
      cattle in the United States.
AB  - Genetic parameters and relative breeding values were estimated for milking speed
      of US Brown Swiss dairy cattle. Owner-recorded milking-speed scores on a scale of
      1 (slow) to 8 (fast) were collected by the Brown Swiss Association as part of its
      linear type appraisal program starting in 2004. Data were 7,366 records for 6,666
      cows in 393 herds. The pedigree file included information for 21,458 animals born
      in 1985 or later. Six unknown-parent groups that each included 4 birth years were
      defined. The model included fixed effects for herd appraisal date and parity
      lactation stage and random effects for permanent environment, animal, and error.
      Within parity (1, 2, and > or =3), 6 groups were defined: unknown calving date,
      four 90-d lactation stages, and lactations with >400 d in milk. Heritability of
      0.22 and repeatability of 0.42 were estimated by average-information REML;
      residual variance was 1.13. Little trend in estimated breeding value was found
      for cows born from 1999 through 2002. Although solutions increased with lactation
      stage for first-parity cows by 0.37, no clear trend was found for later parities.
      Genetic evaluations for milking speed were expressed as relative breeding values
      with a mean of 100 and a standard deviation of 5. The 121 bulls with > or =10
      daughters had milking speed evaluations that ranged from 83 to 112 and had
      correlations of 0.56 with productive life evaluations and -0.40 with somatic cell
      score evaluations. The association of faster milking speed with lower somatic
      cell score was not expected. The moderate heritability found for milking speed
      indicates that the evaluations (first released in May 2006) should be useful in
      detecting bulls with slow-milking daughters.

PMID- 17235181
TI  - Analysis of the sheep MUC1 gene: structure of the repetitive region and
      polymorphism.
AB  - An investigation was undertaken with the aim of studying the repetitive region of
      the MUC1 gene and analyzing its polymorphisms in some Italian sheep breeds. Two
      primers previously used for the goat MUC1 gene analyses allowed for the
      amplification of 4 different alleles. The sequence analysis showed that the
      repetitive region of the sheep MUC1 gene is an array of 60-bp repeats, in
      accordance with the information reported in humans, cattle, and goats. The
      polypeptide sequence encoded by the consensus repeat was very similar to the
      corresponding sequences of goats and cattle. The average homology of all repeated
      units was 82%; when the repeats were compared with the derived consensus repeat,
      homology dropped to 78%. The repeats were not all perfectly conserved, but the
      sequence homology was nevertheless clearly sufficient to preserve the mechanism
      giving rise to the variable-number tandem-repeat polymorphism. In spite of their
      reduced sequence homology, the sheep repeats shared a high number of potential
      glycosylation sites. The conservation of the exact number and position of
      glycosylation sites did not seem to be very important for the purpose of
      functional integrity, but glycosylation appeared to be conserved as a bulk
      property. Analysis of the polymorphism in 6 Italian breeds showed that the sheep
      repetitive region seemed to be less variable and smaller in size than the
      repetitive region of the goat. The findings of this study suggest that ruminants
      can be a useful model to study the mechanisms by which the variation in the
      repeat number and the extracellular domain size can modulate the effectiveness of
      MUC1 as a cell-surface shield.

PMID- 17235182
TI  - Association of bovine leukocyte antigen (BoLA) DRB3.2 with immune response,
      mastitis, and production and type traits in Canadian Holsteins.
AB  - Data collected from 328 Canadian Holsteins in a research herd at the University
      of Guelph were used to study associations among expression of bovine leukocyte
      antigen (BoLA) DRB3.2 alleles, immune response, mastitis resistance via somatic
      cell counts (SCC), and clinical mastitis, as well as to extend these results to
      production and type traits. Accordingly, groups of cows were evaluated in vivo
      for both the antibody-mediated immune response (AMIR) and the cell-mediated
      immune response (CMIR), which generally predominate in responses to extracellular
      and intracellular pathogens, respectively. Of note was that associations between
      BoLA DRB3.2 alleles and immune responses tended to be in the opposite sign for
      the 2 AMIR and CMIR traits examined. For example, alleles DRB3.2*3 and *24 were
      associated with higher AMIR but lower CMIR, whereas allele *22 was associated
      with lower AMIR but higher CMIR. This finding is in agreement with the hypothesis
      that both traits are genetically independent and represent opposing type 1 and
      type 2 immune responses. Additionally, BoLA DRB3.2*3 and *11 were associated with
      lower SCC, whereas alleles *22 and *23 were associated with higher SCC. Finally,
      allele DRB3.2*3 was also associated with less clinical mastitis, whereas allele
      *8 was associated with higher mastitis risk. Allele *3 was of particular
      relevance because it was associated with increased antibodies, as well as reduced
      mastitis and SCC. This could be due to an indirect relationship between the
      ability to produce a high antibody response and enhanced defense against
      intrammamary infections caused by extracellular pathogens. Consequently, the BoLA
      DRB3.2*3 allele should be investigated further as a candidate for resistance to
      some types of intramammary infections, the important caveat being its association
      with lower CMIR, particularly with one of the test antigens used to evaluate
      delayed-type hypersensitivity. The results of associations between BoLA DRB3.2
      and production traits were, in some cases, antagonistic in that BoLA DRB3.2
      alleles *11 and *23, which are associated with increased production traits, were
      associated with lower and higher SCC, respectively. Collectively, these findings
      advocate the use of alleles *3, *23, and *22 as reference points for more
      detailed mechanistic studies. This does not imply that genetic selection for
      mastitis resistance should be based on BoLA alleles, but that information on a
      variety of genes may aid in identification and selection for improved health.

PMID- 17235183
TI  - Goat acetyl-coenzyme A carboxylase alpha: molecular characterization,
      polymorphism, and association with milk traits.
AB  - Acetyl-coenzyme A carboxylase alpha (ACACA), the major regulatory enzyme of fatty
      acid biosynthesis, catalyzes the conversion of acetyl-CoA to malonyl-CoA. We have
      sequenced 5.5 kb of the goat ACACA cDNA in 18 individuals. The translated cDNA
      sequence encodes 1,832 AA and shares a high AA identity (99%) with the ovine and
      bovine ACACA orthologous sequences. One silent single nucleotide polymorphism was
      identified at exon 45 (C5493T). The genotyping of this polymorphism in 4 goat
      breeds, Murciano-Granadina, Teramana, Majorera, and Malaguena, showed that it was
      segregating in all 4 breeds at variable frequencies. In addition, a mixed animal
      model was used to evaluate the association of C5493T genotypes with milk traits.
      Results from this study show that the C5493T mutation was suggestively associated
      with fat yield, lactose content, and somatic cell count.

PMID- 17235184
TI  - Exploring the use of random regression models with legendre polynomials to
      analyze measures of volume of ejaculate in Holstein bulls.
AB  - Artificial insemination centers routinely collect records of quantity and quality
      of semen of bulls throughout the animals' productive period. The goal of this
      paper was to explore the use of random regression models with orthogonal
      polynomials to analyze repeated measures of semen production of Spanish Holstein
      bulls. A total of 8,773 records of volume of first ejaculate (VFE) collected
      between 12 and 30 mo of age from 213 Spanish Holstein bulls was analyzed under
      alternative random regression models. Legendre polynomial functions of increasing
      order (0 to 6) were fitted to the average trajectory, additive genetic and
      permanent environmental effects. Age at collection and days in production were
      used as time variables. Heterogeneous and homogeneous residual variances were
      alternatively assumed. Analyses were carried out within a Bayesian framework. The
      logarithm of the marginal density and the cross-validation predictive ability of
      the data were used as model comparison criteria. Based on both criteria, age at
      collection as a time variable and heterogeneous residuals models are recommended
      to analyze changes of VFE over time. Both criteria indicated that fitting random
      curves for genetic and permanent environmental components as well as for the
      average trajector improved the quality of models. Furthermore, models with a
      higher order polynomial for the permanent environmental (5 to 6) than for the
      genetic components (4 to 5) and the average trajectory (2 to 3) tended to perform
      best. High-order polynomials were needed to accommodate the highly oscillating
      nature of the phenotypic values. Heritability and repeatability estimates,
      disregarding the extremes of the studied period, ranged from 0.15 to 0.35 and
      from 0.20 to 0.50, respectively, indicating that selection for VFE may be
      effective at any stage. Small differences among models were observed. Apart from
      the extremes, estimated correlations between ages decreased steadily from 0.9 and
      0.4 for measures 1 mo apart to 0.4 and 0.2 for most distant measures for additive
      genetic and phenotypic components, respectively. Further investigation to account
      for environmental factors that may be responsible for the oscillating
      observations of VFE is needed.

PMID- 17235185
TI  - Bacterial counts in organic materials used as free-stall bedding following
      treatment with a commercial conditioner.
AB  - An acidic conditioner was tested in recycled manure and sawdust used as free
      stall bedding to determine the effect on bacterial counts of common environmental
      mastitis pathogens. Free stalls were bedded with 10 kg of either kiln-dried
      sawdust or recycled manure per stall. All bedding was removed and fresh bedding
      was applied every 7 d. Approximately 1 kg of commercial bedding conditioner
      containing 93% sodium hydrosulfate (wt/wt) was spread evenly over bedding in the
      back one-third of each treated stall. Control bedding received no treatment. Cows
      were bedded on the same material for 3 consecutive weeks. After 3 wk on a bedding
      treatment, cows remained in the same pens and bedding treatments were changed
      between rows within pens in a switchback design. The addition of bedding
      conditioner to sawdust reduced gram-negative bacterial, coliform, Klebsiella
      spp., and streptococcal counts immediately after application and 1 d after
      application. Bacterial counts did not differ between treated and untreated
      sawdust on d 2 and 6 after the conditioner treatment. Each bacterial count
      measured was reduced in recycled manure immediately after application. Gram
      negative bacterial and streptococcal counts were reduced in treated recycled
      manure compared with untreated recycled manure on d 1 after conditioner was
      applied. Bacterial counts did not differ between treated and untreated recycled
      manure bedding on d 2 and 6 after application in free stalls. The antibacterial
      activity of the conditioner was related to the pH of the bedding and was
      diminished by d 2 after application in both bedding types.

PMID- 17235187
TI  - Voluntary waiting period management practices in dairy herds participating in a
      progeny test program.
AB  - A survey was mailed to approximately 4,000 herds participating in a young sire
      progeny test program to estimate the percentage of herds that selectively alter
      the voluntary waiting period (VWP) for individual cows or groups of cows.
      Responses were received from 673 herds (17%; 583 Holsteins, 55 Jerseys, 35 other
      dairy breeds). The mean VWP cited by respondents was 56 +/- 0.6 d (range = 30 to
      90 d) and did not differ by breed. Among responding herds, 64% (432/673)
      indicated the VWP was selectively altered for one or more reasons. The most
      frequently cited reasons for altering the VWP were postpartum health (50%),
      season (18%), milk yield (18%), parity (14%), and other reasons (14%). In
      Holstein herds that altered the VWP based on milk yield, the highest production
      group averaged 14 more days to first service than the lowest production group (>
      or =40 vs. <20 kg of energy-corrected milk, respectively). In contrast, days to
      first service were nearly identical for all production groups in Holstein herds
      that did not vary the VWP based on milk yield. In conclusion, management
      decisions to selectively alter the VWP led to differences in days to first
      service and may have a confounding effect on genetic estimates of daughter
      fertility. Opportunities to improve the accuracy of daughter pregnancy rate
      estimates may reside in models that adjust for VWP management decisions on a
      within-herd basis.

PMID- 17235186
TI  - The effect of formulation and amount of potassium fertilizer on macromineral
      concentration and cation-anion difference in tall fescue.
AB  - This study investigated the feasibility of altering the dietary cation-anion
      difference (DCAD) in grass by altering the grass variety and the amount and
      formulation of K fertilizer application. In experiment 1, treatments were
      combinations of 2 varieties (Barcel and Hi-Mag) of tall fescue (Festuca
      arundinacea Schreb); 2 rates of K (0 and 250 kg/ha), supplied as KCl; and 2 rates
      of Mg (0 and 60 kg/ha), supplied as MgO. In experiment 2, K fertilizer was
      applied at 0 or 125 kg/ha as KCl or K2SO4. There was no difference between HiMag
      and Barcel tall fescue in the concentrations of Mg, S, and Cl. Application of K
      fertilizer decreased concentrations of Mg, but the magnitude of the decrease was
      not consistent across harvests. Conversely, application of Mg fertilizer
      increased Mg concentrations, but again, the magnitude of the increase was not
      consistent across harvests. The concentrations of Ca were higher in HiMag than in
      Barcel tall fescue, with the magnitude of the difference increasing from first to
      last harvest. Potassium fertilizer decreased Ca concentrations in the first,
      fourth, and fifth harvests only. Calcium concentration was decreased by a greater
      magnitude in HiMag tall fescue as a result of Mg fertilization. The HiMag tall
      fescue contained lower concentrations of K than did Barcel tall fescue in the
      first, second, and third harvests. Application of K fertilizer increased the K
      concentration in all 5 harvests but did not affect Na concentrations except in
      the last harvest. The HiMag tall fescue contained less Na than did Barcel, but
      the magnitude of the difference was affected by K and Mg fertilization.
      Application of K fertilizer decreased S concentrations in first-harvest grass,
      increased concentrations in second-and third-harvest grasses, and had no effect
      in fourth-or fifth-harvest grasses. Application of Mg fertilizer decreased S
      concentrations of tall fescue. Application of K fertilizer increased DCAD values
      for grass harvested from the second through fifth harvests. The increase in DCAD
      attributable to K fertilizer was less in HiMag than in Barcel tall fescue.
      Application of K fertilizer as K2SO4 increased dry matter yield and S
      concentrations of HiMag tall fescue, whereas K applied as KCl increased
      concentrations of K and Cl. There was no effect of fertilizer formulation on Na
      concentrations. The DCAD was lower in HiMag tall fescue fertilized with K2SO4
      compared with that fertilized with KCl. This study showed that DCAD of grass can
      be manipulated by the choice of grass variety, fertilizer formulation, and
      fertilizer application rate.

PMID- 17235190
TI  - Structures of incommensurate and commensurate composite crystals NaxCuO2 (x=1.58,
      1.6, 1.62).
AB  - NaxCuO2 (x approximately 1.6) has been synthesized for different compositions x,
      resulting in both commensurate and incommensurate composite crystals. The crystal
      structures are reported for two incommensurate compounds (x=1.58 and 1.62)
      determined by Rietveld refinements against X-ray powder diffraction data. The
      incommensurate compounds and commensurate Na8Cu5O10 (x=1.6) are found to possess
      similar structures, with valence fluctuations of Cu2+/Cu3+ as the origin of the
      modulations of the CuO2 subsystems; the displacive modulations of Na being
      defined by the closest Na-O contacts between the subsystems. A comparison of the
      structure models obtained from single-crystal X-ray diffraction, synchrotron
      radiation X-ray powder diffraction and X-ray powder diffraction with Cu Kalpha1
      radiation indicates that single-crystal X-ray diffraction is by far the most
      accurate method, while powder diffraction with radiation from an X-ray tube
      provides the least accurate structure model.

PMID- 17235189
TI  - Temperature-dependent crystal structure refinement and 57Fe Mossbauer
      spectroscopy of Cu2Fe2Ge4O13.
AB  - The germanate compound Cu2Fe2Ge4O13, dicopper diiron germanate, was synthesized
      by solid-state reaction at 1403 K and ambient pressure. There is no change of
      space-group symmetry between 10 and 900 K. Between 40 K and room temperature the
      a lattice parameter shows a negative thermal expansion which can be connected to
      a decreasing Cu-Cu interatomic distance. Above room temperature all the lattice
      parameters are positively correlated with temperature. Among the structural
      parameters several alterations with temperature occur, which are most prominent
      for the distorted Fe3+ octahedral site. Besides an increase of the average bond
      length and of the interatomic Fe-Fe distances, distortional parameters also
      increase with temperature, while the average Cu-O bond length remains almost
      constant between 100 and 900 K, as do the average Ge-O distances. 57Fe Mossbauer
      spectroscopy was used to detect long-range magnetic ordering in Cu2Fe2Ge4O13.
      While around 100 K, which is the temperature at which a broad maximum is observed
      in the magnetic susceptibility, no magnetic ordering was detected in the
      Mossbauer spectrum, below 40 K a narrow split sextet is developed which is
      indicative of a three-dimensional magnetic ordering of the sample.

PMID- 17235191
TI  - Structural filiations in the new complex titanates SrLiMTi4O11 (M=Cr, Fe).
AB  - Two new titanates of strontium, lithium and a 3d metal, with the composition
      SrLiMTi4O11 (M=Cr, Fe), have been discovered. Single crystals were obtained by
      spontaneous crystallization from a high-temperature solution with LiBO2 as the
      solvent. The structure of SrLiCrTi4O11 was refined in the orthorhombic space
      group Pnma (Z=4), while SrLiFeTi4O11 appeared to adopt a four-times larger
      orthorhombic unit cell with Pbcn (Z=16). The structures can be described by a
      close-packed arrangement of Sr and O atoms. The unit cell contains six ;compact
      planes' perpendicular to [100] in the layer sequence ABACBC [(chc)2]. Ti and Cr
      or Fe atoms occupy some of the interstitial octahedral sites created, whereas Li
      atoms are in tetrahedral sites. Depending on the synthesis conditions of
      SrLiCrTi4O11, the distribution of Cr and Ti atoms on the four possible
      crystallographic sites is not the same. Having a similar compact-planes sequence,
      SrLiCrTi4O11 and SrLiFeTi4O11 structures differ in the arrangement of Sr and O
      atoms per layer of close packing, which also induces a correlated variation in
      the Li-tetrahedra distribution.

PMID- 17235192
TI  - Ab initio constrained crystal-chemical Rietveld refinement of Ca10(VxP1-xO4)6F2
      apatites.
AB  - Extraction of reliable bond distances and angles for Ca10(VxP1-xO4)6F2 apatites
      using standard Rietveld refinement with Cu Kalpha X-ray powder data was
      significantly impaired by large imprecision for the O-atom coordinates. An
      initial attempt to apply crystal-chemical Rietveld refinements to the same
      compounds was partly successful, and exposed the problematic determination of two
      oxygen-metal-oxygen angles. Ab initio modeling with VASP in space groups P6(3)/m,
      P2(1)/m and Pm showed that both these angular parameters exhibited a linear
      dependence with the vanadium content. Stable crystal-chemical Rietveld
      refinements in agreement with quantum results were obtained by fixing these
      angles at the values from ab initio simulations. Residuals were comparable with
      the less precise standard refinements. The larger vanadium ion is accommodated
      primarily by uniform expansion and rotation of BO4 tetrahedra combined with a
      rotation of the Ca-Ca-Ca triangular units. It is proposed that the reduction of
      symmetry for the vanadium end-member is necessary to avoid considerable
      departures from formal valences at the AII and B sites in P6(3)/m. The
      complementarity of quantum methods and structural analysis by powder diffraction
      in cases with problematic least-squares extraction of the crystal chemistry is
      discussed.

PMID- 17235193
TI  - Multipole refinement and electron density analysis in natural borosilicate
      datolite using X-ray diffraction data.
AB  - The electron density distribution in the layer silicate datolite, Ca[BOH(SiO4)],
      was analyzed using high-precision single-crystal X-ray diffraction data (Mo
      Kalpha, T=293 K). The Hansen-Coppens multipole model and Bader's topological
      analysis of the electron density provides a basis for the quantitative
      characterization of the bonded interaction of datolite. The results are presented
      both in the form of maps of the electron density distribution and its Laplacian,
      and in a compact way in terms of the critical points of the electron density. The
      relative electronegativities are also discussed. It was shown that closed-shell
      type interactions exist between Ca and O atoms, whereas Si-O and B-O bonds
      exhibit an intermediate nature with a strong covalent component. An analysis of
      the topology of the electrostatic potential demonstrates the relevance of
      considering this physical property to obtain a complete picture of structure
      forming factors.

PMID- 17235194
TI  - Structure of an aluminophosphate EMM-8: a multi-technique approach.
AB  - The crystal structure of an aluminophosphate, EMM-8 (ExxonMobil Material #8), was
      determined in its calcined, anhydrous form from synchrotron powder diffraction
      data using the computer program FOCUS. A linkage of double four-ring (D4R)
      building units forms a two-dimensional framework with 12-MR and 8-MR channels,
      and differs from a similar SAPO-40 (AFR) framework only by the relationship
      between paired D4R units. Rietveld refinement reveals a fit of the model to the
      observed synchrotron data by Rwp=0.1118, R(F2)=0.1769. Local environments of the
      tetrahedral phosphorus and aluminium sites were established by solid-state NMR,
      which detects distinct differences between as-synthesized and calcined materials.
      Distinct, reversible changes in the local symmetry of the P and Al atoms were
      observed by NMR upon calcination and subsequent hydration. These NMR data
      provided important constraints on the number of tetrahedral (T) atoms per unit
      cell and the connectivities of the T atoms. Detailed local structural information
      obtained by solid-state NMR thereby guided the ultimate determination of the
      structure of AlPO EMM-8 from the powder data. Comparisons are made to the
      recently published crystal structure of the fluoride-containing, as-synthesized
      SSZ-51, indicating that the unit-cell symmetry, axial dimensions and framework
      structure are preserved after calcination.

PMID- 17235195
TI  - Structure of the novel ternary hydrides Li4Tt2D (Tt=Si and Ge).
AB  - The crystal structures of newly discovered Li4Ge2D and Li4Si2D ternary phases
      were solved by direct methods using neutron powder diffraction data. Both
      structures can be described using a Cmmm orthorhombic cell with all hydrogen
      atoms occupying Li6-octahedral interstices. The overall crystal structure and the
      geometry of these interstices are compared with those of other related phases,
      and the stabilization of this novel class of ternary hydrides is discussed.

PMID- 17235196
TI  - Sensitive detection of mirror symmetry by CBED applied to LaAlO3 and GdAlO3.
AB  - Convergent-beam electron diffraction (CBED) patterns tilted away from major zone
      axes have been used to re-examine the space groups of LaAlO3 and GdAlO3
      perovskites. The higher-order Laue zones (HOLZ) in CBED patterns at such tilted
      orientations have been found to have high sensitivity to the presence of mirror
      symmetry. This sensitivity has enabled the space group of LaAlO3, previously
      claimed to be cubic (Fm3c), to be confirmed as rhombohedral R3c by CBED. It is
      clear that patterns of sufficient tilt will be more sensitive for distinguishing
      between screw axes and glide planes than the observation of HOLZ deficit lines in
      zero-order Laue zone reflections. No symmetry degrading effects due to the
      influence of tilted crystal surfaces could be observed.

PMID- 17235197
TI  - Structure determination of di-mu-hydroxo-bis[(2-(2-pyridyl)phenyl
      kappa2N,C1)palladium(II)] by X-ray powder diffractometry.
AB  - The title compound was synthesized in the form of a powder, and was studied by
      elemental analysis, IR spectroscopy, thermogravimetry and mass spectroscopy. Its
      crystal structure was then determined by X-ray powder diffractometry, using X-ray
      diffraction data collected in the reflection Bragg-Brentano geometry. The
      methodology followed in the present study to resolve the crystal structure
      consisted of peak indexing, then the use of the Monte-Carlo/parallel tempering
      search algorithm, and finally Rietveld refinement coupled with difference-Fourier
      synthesis. We found that the crystals are composed of monoclinic unit cells, with
      1.5 molecules in the asymmetric unit and therefore six molecules per unit cell.
      In addition, we concluded that the complexes adopt a planar conformation, forming
      trimers created by groups of parallel molecules.

PMID- 17235198
TI  - Extended structures of polyiodide salts of transition metal macrocyclic
      complexes.
AB  - The structures of five polyiodide salts, [Co([9]aneS3)2]I11 (1),
      [Ni([9]aneS3)2]I6 (2), [Ni([9]aneS3)2]I10 (3), [Pd([12]aneS4)]I6 (4) and
      [Pd([14]aneS4)]I10.MeCN (5), containing the template cations [Co([9]aneS3)2]3+,
      [Ni([9]aneS3)2]2+, [Pd([12]aneS4)]2+ and [Pd([14]aneS4)]2+ ([9]aneS3=1,4,7
      trithiacyclononane, [12]aneS4=1,4,7,10-tetrathiacyclododecane, [14]aneS4=1,4,8,11
      tetrathiacyclotetradecane) exhibit a range of polyiodide and polyanionic
      framework structures. In (1) the charge on the CoIII cation is balanced by three
      I3- anions, which along with a neutral di-iodine molecule form I(11)3- rings in
      an extended structure comprising undulating chains of alternating I11(3-) rings
      and complex cations. In (2) the complex cation is linked to two tri-iodide anions
      by S...I interactions into well separated sheets of cations and anions, while in
      (3), I5- anions are linked by I...I interactions into helices which are cross
      linked by S...I contacts to form sheets. Rather longer I...I contacts in (4)
      assemble I3- ions into 2x2 rods, which are linked into a three-dimensional
      network by S...I contacts. In (5) the N atom of the acetonitrile solvent molecule
      forms an array of four weak C-H...N hydrogen bonds to the macrocycle. The
      extended structure comprises corrugated zigzag chains of polyiodide rings formed
      by linked I_5;- units; the complex cations are attached to the polyiodide network
      by S...I contacts, which link the chains to form layers.

PMID- 17235199
TI  - Low-temperature enantiotropic k2 phase transition in the ionic 222-cryptand
      complex with LiClO4.
AB  - Crystallographic analyses at 100 and 200 K are reported for the macrobicyclic
      polyether 4,7,13,16,21,24-hexaoxa-1,10-diaza-bicyclo[8.8.8]hexacosane (denoted as
      222-cryptand) that encapsulates a Li+ cation and then forms a complex (I) with
      ClO4-. Compound (I) undergoes a reversible second-order k phase transition at 253
      (2) K from an almost ordered structure [space group P2(1)2(1)2(1)] at 100 K to a
      more disordered structure that exhibits a different unit cell [P2(1)2(1)2
      (2c'=c)] above 253 (2) K. At 295 K the Li+ cation and five atoms of the
      perchlorate anion are each disordered over at least two positions about a
      crystallographic twofold axis [Chekhlov (2003). Russ. J. Coord. Chem. 29, 828
      832]; as the temperature decreases the dynamic positional disorder is slowly
      frozen out, but is still observed for lithium even at 100 K. Based upon DFT
      computations, it seems that in the solid state the position of the Li+ cation in
      the cavity of the 222-cryptand below 253 (2) K likely corresponds to a local
      energy minimum; the global minimum in the gas phase corresponds to a near D3
      symmetrical conformation of the 222-cryptand with the undersized Li+ cation
      residing in the center of its cavity.

PMID- 17235200
TI  - Three isomeric 1-(2-chloronicotinoyl)-2-(nitrophenyl)hydrazines, including three
      polymorphs of 1-(2-chloronicotinoyl)-2-(2-nitrophenyl)hydrazine: hydrogen-bonded
      supramolecular structures in two and three dimensions.
AB  - 1-(2-Chloronicotinoyl)-2-(2-nitrophenyl)hydrazine, C12H9ClN4O3, crystallizes in
      three polymorphic forms, two monoclinic forms in space groups Cc (Ia) and P2(1)
      (Ib), and an orthorhombic form in space group Pbcn (Ic). In the Cc polymorph (Ia)
      the molecules are linked into sheets by combinations of one N-H...O and two C
      H...O hydrogen bonds, while in the P2(1) polymorph (Ib) the molecules are linked
      into sheets by combinations of three hydrogen bonds, one each of N-H...O, C-H...N
      and C-H...O types. In the orthorhombic polymorph (Ic) the molecules are linked
      into a complex three-dimensional framework structure by a combination of one N
      H...O, one N-H...N and three C-H...O hydrogen bonds, and an aromatic pi...pi
      stacking interaction. In the isomeric compound 1-(2-chloronicotinoyl)-2-(3
      nitrophenyl)hydrazine (II) the molecules are again linked into a three
      dimensional framework, this time by a combination of three hydrogen bonds, one
      each of N-H...O, N-H...N and C-H...O types, weakly augmented by a pi...pi
      stacking interaction. The molecules of 1-(2-chloronicotinoyl)-2-(4
      nitrophenyl)hydrazine (III) are linked into sheets by a combination of three
      hydrogen bonds, one each of N-H...O, N-H...N and C-H...O types.

PMID- 17235201
TI  - In-situ high-pressure study of the ordered phase of ethyl propionate.
AB  - Ethyl propionate, C5H10O2 (m.p. 199 K), has been in-situ pressure-frozen and its
      structure determined at 1.34, 1.98 and 2.45 GPa. The crystal structure of the new
      high-pressure phase (denoted beta) is different from phase alpha obtained by
      lowering the temperature. The freezing pressure of ethyl propionate at 296 K is
      1.03 GPa. The molecule assumes an extended chain s-trans-trans-trans
      conformation, only slightly distorted from planarity. The closest intermolecular
      contacts in both phases are formed between carbonyl O and methyl H atoms;
      however, the ethyl-group H atoms in phase beta form no contacts shorter than 2.58
      A. A considerable molecular volume difference of 24.2 A3 between phases alpha and
      beta can be rationalized in terms of degrees of freedom of molecules arranged
      into closely packed structures: the three degrees of freedom allowed for
      rearrangements of molecules confined to planar sheets in phase alpha, but are not
      sufficient for obtaining a densely packed pattern.

PMID- 17235202
TI  - Pitfalls of data mining: triclinic polymorph of 2,2-aziridinedicarboxamide
      revisited.
AB  - Several procedures have been employed for validating structural models refined on
      poor quality single-crystal diffraction data. Analysis of intra- and
      intermolecular distances in the structures of 2,2-aziridinedicarboxamide
      polymorphs proved to be a robust means, and a means independent of the chosen
      unit cell and symmetry, of detecting several incorrect atom-type assignments in
      the reported structure of the triclinic polymorph of 2,2-aziridinedicarboxamide
      [Bruckner (1982). Acta Cryst. B38, 2405-2408]. The corrected model, refined in
      the space group P1, rules out the existence of any conformational polymorphism in
      this compound. Small differences in the powder-diffraction patterns calculated
      for the original and corrected structures of the triclinic polymorph illustrate
      the sensitivity of the above method for polymorph validation.

PMID- 17235203
TI  - Halogen...halogen interactions in pressure-frozen ortho- and meta-dichlorobenzene
      isomers.
AB  - Isomers 1,2-dichlorobenzene (o-DCB) and 1,3-dichlorobenzene (m-DCB) were high
      pressure frozen in-situ in a Merrill-Bassett diamond-anvil cell and their
      structures determined at room temperature and at 0.18 (5) GPa for o-DCB, and 0.17
      (5) GPa for m-DCB by single-crystal X-ray diffraction. The patterns of
      halogen...halogen intermolecular interactions in these structures can be
      considered to be the main cohesive forces responsible for the molecular
      arrangements in these crystals. The molecular packing of dichlorobenzene isomers,
      including three polymorphs of 1,4-dichlorobenzene (p-DCB), have been compared and
      relations between their molecular symmetry, packing arrangements, intermolecular
      interactions and melting points discussed. The topology of the crystal packing in
      dichlorobenzene isomers results from the interplay of the molecular shape, steric
      hindrances and intermolecular interactions. The non-planar arrangement of the
      dichlorobenzene molecules in the crystal structures can be justified by the
      distributions of the electrostatic potential on molecular surfaces, which
      determines electrostatic intermolecular interactions.

PMID- 17235204
TI  - Analysis of structures with saturated hydrogen bonding.
AB  - All simple structures with saturated hydrogen bonding (SHB) are classified into
      eight categories on the basis of the donor and acceptor numbers on the atoms at
      each end of the hydrogen bonds. Examples from the literature are included where
      known, along with seven structures investigated as part of this study (five have
      SHB). Graph-set descriptions of the hydrogen-bond patterns are given for each of
      these structures and for some selected literature examples. The structures
      presented are: piperazine (I), morpholinium chloride (II) and iodide (III) [(II)
      and (III) are not SHB], three 1:1 cocrystals of diols with 1,4-phenylenediamine
      (PDA)--PDA.1,8-octane diol (IV), PDA.1,10-decane diol (V), and PDA.1,12-dodecane
      diol (VI) and 6-amino-1-hexanol (VII). This study discusses some structures that
      show limitations of the graph-set model, along with possible suggestions to cover
      these limitations. The cocrystalline PDA.aliphatic diol structures may provide
      details applicable to the structure of self-assembled monolayers of aliphatic
      thiol molecules on Au(111) surfaces.

PMID- 17235205
TI  - Determination of covalent bond orders and atomic valence indices using
      topological features of the experimental electron density.
AB  - We present an approach for the determination of covalent bond orders from the
      experimental electron density and its derivatives at the bond critical points. An
      application of this method to a series of organic compounds has shown that it
      provides a bonding quantification that is in reasonable agreement with that
      obtained by orbital theory. The 'experimental' atomic valence indices are also
      defined and their significance for the characterization of chemical problems is
      discussed.

PMID- 17235206
TI  - Structural study of four complexes of the M-N2S2 type derived from
      diethylphenylazothioformamide and the metals palladium, platinum, copper and
      nickel.
AB  - The four electron-transfer complexes trans-(di(N,N-diethyl-(2
      phenyldiazenyl)thioformamide-kappaS,kappaN2))nickel, trans-(di(N,N-diethyl-(2
      phenyldiazenyl)thioformamide-kappaS,kappaN2))copper, trans-(di(N,N-diethyl-(2
      phenyldiazenyl)thioformamide-kappaS,kappaN2))palladium and trans-(di(N,N-diethyl
      (2-phenyldiazenyl)thioformamide-kappaS,kappaN2))platinum have been crystallized,
      and their structures have been determined at low temperature. All the complexes
      are of the M-N2S2 type. The crystals of both the nickel and the copper complex
      belong to the tetragonal P4(1)2(1)2 system, in which the central metal ion lies
      on a twofold axis. The tetrahedral molecular symmetry around the central metal
      ion is unusual for the M-N2S2 electron-transfer complexes. The crystals of the
      palladium and platinum complexes on the other hand belong to the monoclinic C2/c
      system in which the metal ion lies on an inversion centre. The molecular symmetry
      around these metal ions is square planar. It is demonstrated that the pi electron
      density in the ligand planes has a high degree of delocalization. Furthermore,
      unusually large line broadening of the 1H NMR spectra was observed and
      investigated as a function of temperature for the palladium complex.

PMID- 17235207
TI  - Cu3MgCl2(OH)6 and the bond-valence parameters of the OH-Cl bond.
AB  - The title compound is a new mineral consisting of sheets made from edge-sharing
      Cu(OH)4Cl2 and Mg(OH)6 octahedra. The sheets are only weakly linked by O-H-Cl
      bridges, giving rise to perfect cleavage along (001) and to strong texture
      effects in powder diffraction measurements. Owing to low bond-valence sums at the
      Cl sites of Cu3MgCl2(OH)6 and of several related compounds, bond-valence
      parameters for the H/Cl pair have been refined to R0=1.336 and b=0.53 A based on
      the crystal structures of selected hydroxychlorides.

PMID- 17235210
TI  - Alternative methods of estimating an incubation distribution: examples from
      severe acute respiratory syndrome.
AB  - BACKGROUND: Accurate and precise estimates of the incubation distribution of
      novel, emerging infectious diseases are vital to inform public health policy and
      to parameterize mathematical models. METHODS: We discuss and compare different
      methods of estimating the incubation distribution allowing for interval censoring
      of exposures, using data from the severe acute respiratory syndrome (SARS)
      epidemic in 2003 as an example. RESULTS: Combining data on unselected samples of
      149 and 168 patients with defined exposure intervals from Toronto and Hong Kong,
      respectively, we estimated the mean and variance of the incubation period to be
      5.1 day and 18.3 days and the 95th percentile to be 12.9 days. We conducted
      multiple linear regression on the log incubation times and found that incubation
      was significantly longer in Toronto than in Hong Kong and in older compared with
      younger patients, while it was significantly shorter in healthcare workers than
      in other patients. CONCLUSIONS: Our findings suggest subtle but important
      heterogeneities in the incubation period of SARS among different strata of
      patients. Robust estimation of the incubation period should be independently
      carried out in different settings and subgroups for novel human pathogens using
      valid statistical methods.

PMID- 17235211
TI  - Statin use and the risk of 10 cancers.
AB  - BACKGROUND: Statins affect the proliferation, survival, and migration of cancer
      cells, and it is thought that they may have chemopreventive properties in humans.
      The purpose of the present study was to evaluate the association between statin
      use and various types of cancer in our hospital-based case-control surveillance
      study. METHODS: Data were collected from patients ages 40-79 years who were
      admitted to participating hospitals in 3 centers in Philadelphia, New York, and
      Baltimore from 1991 to 2005. Nurses administered questionnaires to obtain
      information on medication use and other factors. We compared patients who had any
      of 10 types of cancer (a total of 4913 patients) with controls admitted for
      noncancer diagnoses (3900 patients). The following cancers were examined
      individually: female breast (n = 1185), prostate (n = 1226), colorectal (n =
      734), lung (n = 464), bladder (n = 240), leukemia (n = 254), pancreas (n = 220),
      kidney (n = 226), endometrial (n = 220), and non-Hodgkin lymphoma (n = 144).
      Logistic regression models were used to estimate odds ratios and 95% confidence
      intervals among regular statin users compared with never-users. RESULTS: Odds
      ratios were compatible with 1.0 for all cancer types. For the 4 largest cancer
      sites (breast, prostate, colorectum, and lung), odds ratios did not vary
      significantly by duration of statin use. CONCLUSIONS: Statins are among the most
      commonly used medications, and durations of use are increasing. The present data
      do not support either positive or negative associations between statin use and
      the occurrence of 10 cancer types. Cancer incidence should continue to be
      monitored among statin users.

PMID- 17235212
TI  - Lifestyle behaviors in women with a BRCA1 or BRCA2 genetic mutation: an
      exploratory study guided by concepts derived from the Health Belief Model.
AB  - Lifestyle behaviors have not been adequately addressed as potential cancer risk
      reduction strategies in women with BRCA1 or BRCA2 genetic mutations. The aims of
      this qualitative pilot study were to explore current lifestyle practices among
      these women and to assess perceptions regarding risk as well as perceived
      benefits and perceived barriers to engage in healthy behaviors. Qualitative
      descriptive methodology was used with research questions derived from key Health
      Belief Model concepts. Interviews were conducted with 10 women recruited through
      a cancer genetics clinic. Interviews were tape-recorded and transcribed for
      content analysis of common themes and patterns. All of the participants expressed
      that they were at high risk for cancer; however, 5 of the women had prophylactic
      surgery, which decreased their sense of risk. Most women made some healthy
      behavior change as a result of their elevated risk awareness. Perceived benefits
      to healthy lifestyles included increased energy and improved mood. Perceived
      barriers were related to the expense and inconvenience of preparing healthy meals
      and lack of time to exercise. The findings reveal that there is a need for
      nursing interventions that may improve education and enhance motivation regarding
      potential lifestyle risk-reduction behaviors in women with a genetic
      predisposition for breast and ovarian cancer.

PMID- 17235213
TI  - Patient-reported family distress among long-term cancer survivors.
AB  - Two quality of life studies at the University of Nebraska Medical Center and 3
      similar studies in the nursing literature were compared regarding family distress
      to illness scores as reported by long-term cancer survivors. All studies were
      cross-sectional mail surveys and used City of Hope National Medical Center
      questionnaires. Participants represented a broad range of survivorship in terms
      of diagnosis and length of survival (range of means 3Y8 years). Single-item
      scores were compared among participants regarding the item "How distressing has
      your illness been for your family?" Significant levels of patient-reported family
      distress to illness were reported in all 5 studies. Patient survivors may have
      been able to recall past levels of significant family distress despite prolonged
      survival or they may have reported significant ongoing family distress as a
      result of their disease and treatment. Longitudinal assessment of patients' and
      families' quality of life is essential throughout survivorship. Future studies
      should identify and compare the types distress experienced by patient survivors
      and families over time and also measure the intensity of their distress.
      Interventions designed to meet their individual and collective needs, thereby
      decreasing their distress, are needed to improve quality of life for survivors
      and families.

PMID- 17235214
TI  - Health-related goals in female cancer survivors after treatment.
AB  - Researchers often have studied cancer treatments and psychosocial aspects of
      dealing with cancer, but seldom have they evaluated cancer survivors at the end
      of their treatments or survivors' health-related goals. The purpose of the study
      was to identify the health-related goals of female cancer survivors at this phase
      of survivorship. Participants (N = 51) were women who were aged 34 to 77 years
      and had finished radiation and/or chemotherapy for primary breast or gynecologic
      cancers. Using a longitudinal design, interviews were conducted within 4 weeks
      and 3 to 4 months after treatment. Participants answered open-ended questions
      about their health-related goals. Content analyses were performed on
      participants' responses. Across interviews, the most common goals were improving
      physical activity (54-56% in first and second interviews, respectively),
      performing meaningful activities (26-27%), losing weight (21-22%), and eating a
      better diet (16-22%). Clinicians can assess for such common goals and address
      them, as needed, among women with breast or gynecologic cancer. Researchers could
      design and test the effect of interventions designed to address patients' goals
      on behavioral and health outcomes among similar cancer survivors.

PMID- 17235215
TI  - Body experience and reliance in some women diagnosed with cancer.
AB  - Physical disease, like cancer, can be perceived as a psychological crisis. Part
      of this crisis concerns changes in the body. The aim of this study was to
      describe the phenomenon "body experience" with special attention to "body
      reliance" among women with cancer. Participants were 10 women with different
      cancer diagnoses who had been under oncological medical care or were receiving
      treatment to palliate cancer symptoms. All were scheduled to begin
      physiotherapeutic rehabilitation. Semistructured interviews were conducted and
      analyzed from a phenomenological-hermeneutical point of view. Cancer caused a
      radical change on many levels. A new sensitivity to bodily signals developed,
      which could be related to insecurity associated with the disease and the
      treatment. Many worried greatly about a recurrence. This was related to a
      questioning of trust in the body and in life. There was an existential dimension
      in listening to the body's signals: the body was transformed into a messenger in
      a wide sense. It was meaningful to investigate the cancer experience from a
      bodily perspective. The results indicate that it can be helpful to communicate
      with the patient regarding body experience in cancer rehabilitation.

PMID- 17235216
TI  - Fatigue and its associated factors in hospice cancer patients in Taiwan.
AB  - Fatigue is one of the most distressful problems faced by terminally ill cancer
      patients, but few studies have explored fatigue experiences in this population.
      The purpose of this descriptive correlational study was to examine fatigue status
      and its related factors in terminally ill cancer patients in an institutionalized
      hospice in Northern Taiwan. Data were collected using the Fatigue subscale of the
      Profile of Mood States, modified Symptom Distress Scale, Hospital Anxiety and
      Depression Scale, Karnofsky's Performance Status Index and a background
      information form. We found that patients generally had moderate to severe levels
      of fatigue. Fatigue was associated with the overall symptom distress, depression,
      anxiety, and performance status. Furthermore, fatigue was significantly
      correlated with 8 individual distressful symptoms: nausea, vomiting, lack of
      appetite, sleep disturbance, dyspnea, dry mouth, restlessness, and problems of
      concentration. These results suggest that fatigue is still a problem faced by
      terminally ill cancer patients. To provide better care to this population, the
      above-mentioned fatigue-related factors should be simultaneously assessed and
      cared for. The authors recommend examining the causal relationship between these
      factors and fatigue, using symptom cluster concepts and skills to examine the
      possible shared mechanisms among fatigue and related symptoms and developing
      interventions to decrease fatigue in terminally ill cancer patients.

PMID- 17235217
TI  - Knowledge of and barriers to pain management in caregivers of cancer patients
      receiving homecare.
AB  - Cancer treatment is increasingly being provided in outpatient settings, requiring
      many of the responsibilities for patient care to be undertaken by family
      caregivers. Pain is one of the most frequent and distressing symptoms experienced
      by cancer patients and is a primary concern for the family caregiver. Caregivers
      struggle with many issues that lead to inadequate management of cancer pain. The
      purpose of this study was to determine pain management knowledge and examine
      concerns about reporting pain and using analgesics in a sample of primary family
      caregivers of cancer patients receiving homecare. The Barriers Questionnaire and
      the Family Pain Questionnaire were administered to 46 primary caregivers. Between
      46% and 94% of the caregivers reported having at least some agreement with the
      various concerns that are barriers to reporting pain and using analgesics, and up
      to 15% reported having strong agreement. The areas of greatest concern were about
      opioid-related side effects, fears of addiction, and the belief that pain meant
      disease progression. Results showed that caregivers with higher pain management
      knowledge had significantly fewer barriers to cancer pain management, supporting
      the importance of increasing caregiver's knowledge of management of cancer pain.

PMID- 17235218
TI  - Complementary and alternative medicine use in pediatric oncology patients in
      eastern Turkey.
AB  - The use of complementary and alternative medicines (CAM) among children with
      cancer is becoming increasingly popular. Therefore, it is important to gain
      insight into the prevalence and factors related to the use of CAM. This study
      presents findings from a study of parents of 88 children with cancer who were
      receiving or had received conventional therapy for treatment of childhood cancer
      at a pediatric oncology unit in eastern Turkey. The findings indicated that 48.9%
      of the respondents reported the use of 1 or more CAM therapies. The most commonly
      used modality was herbal products such as herbal tea and herbal meal, mostly
      stinging nettle (Urtica dioica). The findings of this study indicate that CAM
      users were children who were an average of 3 years older than nonuser children
      and that CAM use was more prevalent among the children who had been diagnosed
      with cancer for a longer time than nonusers. There were no significant difference
      between users and nonusers regarding sociodemographic characteristics (such as
      age education level, economic status), hopelessness score of parents, gender of
      child, and treatment status. Healthcare providers should remain informed about
      the benefits and adverse effects of complementary and alternative therapies to
      discuss treatment options with patients and their families and to monitor
      treatment efficacy.

PMID- 17235219
TI  - Use of complementary and alternative medicine therapies to control symptoms in
      women living with lung cancer.
AB  - Complementary and alternative medicine (CAM) use by cancer patients, especially
      women, is increasing. However, CAM use among patients with lung cancer, who have
      been reported to have the highest symptom burden, is poorly documented. This
      study describes types and frequencies of specific CAM therapies used by women
      with lung cancer to manage symptoms, and examines differences in demographic and
      clinical characteristics between CAM users and non-CAM users. Participants
      included 189 women with non-small cell lung cancer and > or =1 of 8 symptoms. Six
      CAM therapies, used to control symptoms, were assessed, including herbs, tea,
      acupuncture, massage, meditation, and prayer. Forty-four percent (84 women) used
      CAM therapies, including prayer (34.9%), meditation (11.6%), tea (11.6%), herbs
      (9.0%), massage (6.9%), and acupuncture (2.6%). Complementary and alternative
      medicine use was greatest for difficulty breathing and pain (54.8% each), with
      prayer the most commonly used CAM for all symptoms. Significant differences (P <
      .05) were found for age (t = 2.24), symptom frequency (t = -3.02), and geographic
      location (chi = 7.51). Women who were younger, experienced more symptoms, and
      lived on the West Coast or South (vs Northeast) were more likely to use CAM. We
      found that CAM use is variable by symptom and may be an indicator of symptom
      burden. Our results provide important initial data regarding CAM use for managing
      symptoms by women with lung cancer.

PMID- 17235222
TI  - The impact of inadequate knowledge on patient and spouse experience of prostate
      cancer.
AB  - The aim of this study is to describe the impact of patient knowledge and
      awareness of prostate cancer on their medical process from initial symptom
      detection to post treatment. Although research is gradually increasing in
      relation to prostate cancer, limited attention has been paid to the impact of
      inadequate knowledge on patient and spouse experience of the medical process
      despite the often complex and varied nature of the disease trajectory, treatment,
      and outcomes. An in-depth focus group design that incorporates open-structured
      questions was used to identify the attitudes and experiences of a sample of 12
      prostate cancer patients and spouses. The findings of this study show that
      inadequacies in patient and spouse knowledge and awareness of prostate cancer
      contributed to delayed contact, shock at diagnosis, preferences regarding
      decision making, health judgments, including the use of the Prostate Specific
      Antigen test and physical well-being as accurate health indicators, and patient
      coping, incorporating the use of comparison with other patients. In conclusion,
      hospital staff, in particular the consultant and cancer nurse specialist, must be
      aware of the potential for inadequacy in patient and spouse knowledge and counter
      this through the provision of accurate and relevant information and support
      throughout the medical process. A series of recommendations have been generated.

PMID- 17235223
TI  - Breast self-examination among Polish women of procreative age and the attached
      significance.
AB  - The aim of the study was to check whether and how frequently Polish women of
      procreative age examine their breasts, what this is conditioned by, and whether
      such self-examination has diagnostic significance. In this study, survey by
      questionnaire of 492 women of procreative age was conducted. Breast self
      examination (BSE) was conducted by 82.9% of the respondents, out of which 33.7%
      conducted regular monthly examinations. The demographic variables assumed in this
      study proved to be statistically significant (P < .05) for younger single women
      with medical education and living under conditions of higher economic standard.
      The diagnostic significance attached to BSE was closely connected with the
      professional background of the respondents and the actual conducting of BSE. An
      opinion that BSE has diagnostic value was expressed in the group of medical
      professionals significantly more frequently than in the group of women
      representing other professions (P = .0000009). Such an opinion was also held
      significantly more often in the group of women performing BSE than in the group
      of women who had no such habit (P < .0000001). A majority of women of procreative
      age perform BSE; however, only a third perform that regularly, every month.
      Factors determining the conduction of BSE include age, profession, marital
      status, and standard of living conditions. The diagnostic significance attached
      to BSE is closely connected with the professional background of the respondents
      and actual conducting of BSE. Breast self-examination has not been satisfactorily
      popularized among Polish women. Greater involvement in educational activities of
      medical personnel may improve the present situation.

PMID- 17235224
TI  - Adaptation of Champion's Health Belief Model Scale for Turkish women and
      evaluation of the selected variables associated with breast self-examination.
AB  - The purpose of this study was to adapt Champion's Revised Health Belief Model
      Scale for Turkish women and to examine selected sociodemographic variables
      associated with breast self-examination (BSE). Data were collected from a total
      of 430 females who were living in one of the Health Center areas located in
      Izmir, a city in the west of Turkey. Champion's revised Health Belief Model Scale
      was translated into Turkish, validated by professional judges, translated back
      into English, and then tested. Factor analysis yielded 7 factors: susceptibility,
      seriousness, barrier 1, barrier 2, confidence, benefits, and health motivation.
      Significant correlations were found between 2 barriers. Therefore, 2 barriers
      were considered one barrier subscale. All the items on each factor were from the
      same construct. Cronbach alpha coefficients ranged from .58 to .89, and test
      retest reliability coefficients ranged from .89 to .99 for the subscales. Women
      who received low scores on barriers reported greater frequency of BSE practice.
      Likewise, women having high scores on confidence, benefits, health motivation,
      susceptibility, and seriousness reported a greater frequency of BSE in the last
      year. The frequency of BSE practice was higher in high school and university
      graduates, women with a family history of breast cancer, and women with breast
      cancer and BSE training. The Turkish version of Champion's Revised Health Belief
      Model Scale was found to be a valid and reliable tool for use with Turkish women.
      It could be used to evaluate health beliefs about breast cancer and BSE among
      Turkish women.

PMID- 17235225
TI  - Knowledge, barriers, and facilitators of Korean women and their spouses in the
      contemplation stage of breast self-examination.
AB  - The aim of this study was to identify the knowledge, barriers, and facilitators
      of breast self-examination (BSE) in Korean couples in the contemplation stage.
      The study design was based on assumptions from the Health Belief Model and
      Transtheoretical Model that contemplators perceiving benefits as greater than
      barriers are likely to move to the next stage. Participant couples, with wives
      having never practiced BSE but with an intention to do so, were drawn from
      churches. Qualitative research was conducted with focus group methodology
      including both husbands and wives in the groups. Data transcribed from audiotapes
      were analyzed to identify common themes. Knowledge of breast cancer and BSE
      included "perceiving risks of getting breast cancer," "behaviors used to stay
      healthy and detect breast cancer," and "skills in BSE"; barriers to BSE included
      "lack of sensitivity to breast cancer," "fear of getting bad news," "lack of
      information," and "shortage of time"; and facilitators of BSE included "making
      BSE a monthly routine," "continuous systematic interaction from healthcare
      professionals reaching out to the community," and "encouragement and help from
      husbands." To improve compliance with BSE, women in the contemplation stage need
      specific and correct knowledge delivered by diverse materials, reminders, and the
      inclusion of husbands as facilitators.

PMID- 17235226
TI  - Unmet service needs of persons with traumatic brain injury.
AB  - OBJECTIVES: Assess unmet needs of persons with traumatic brain injury (TBI) 1
      year after hospital discharge; compare perceived need with needs based on
      deficits (unrecognized need); determine major barriers to services; evaluate
      association of needs with satisfaction with life. PARTICIPANTS: Representative
      sample of 1830 community-dwelling persons with TBI aged 15 years and older.
      MEASURES: Perceived and unrecognized unmet needs, barriers to receiving services,
      and satisfaction with life as a function of met service needs. RESULTS: 35.2% of
      participants reported at least 1 unmet need, 51.5% had unrecognized needs, 47%
      reported at least 1 barrier to receiving help. Receipt of services significantly
      increased satisfaction with life. CONCLUSIONS: Many persons experiencing TBI
      report having unmet service needs 1 year after hospital discharge.

PMID- 17235227
TI  - A qualitative needs assessment of persons who have experienced traumatic brain
      injury and their primary family caregivers.
AB  - OBJECTIVES: To determine the expressed needs of persons with traumatic brain
      injury (TBI) and their primary family caregivers. DESIGN: Semistructured
      interviews with content-analytic techniques to identify respondents' needs.
      PARTICIPANTS: Eighty persons with TBI, with an average time since their most
      severe TBI of 5.8 years, and 85 primary support persons. RESULTS: Respondents
      described their needs via phases that paralleled transitions in settings,
      treatments, and responsibilities (ie, acute care, in-patient rehabilitation,
      return home, and living in the community). Prominent themes during in-patient
      phases included provider quality, emotional support, and understanding the
      injuries. Prominent themes during the latter 2 phases included guidance, life
      planning, community integration, and behavioral and emotional issues.
      CONCLUSIONS: Participants reported insufficient education and preparation for the
      future. Current methods of identifying needs may not be based on these
      populations' perceptions, and often miss the natural divisions of needs that
      occur over the course of treatment and rehabilitation. To meet their needs,
      services must be responsive to changes in needs over time, accessible to
      consumers of services for as long as they are required, and designed to be
      directed and customized by users.

PMID- 17235228
TI  - Interpreting activity of daily living errors for treatment and discharge
      planning: the perception of occupational therapists.
AB  - OBJECTIVES: As clinician ratings of performance-based assessments of activities
      of daily living (ADL) require examiners to judge the appropriateness of actions
      within task context, this study sought to document occupational therapists'
      (OTs') ability to distinguish examples of potential ADL errors of healthy adults
      (HA) from those of individuals with frontal lobe lesions (FLL). METHOD: Eighty
      two OTs were asked to identify the likely source population (HA/FLL) associated
      with 26 ADL errors. RESULTS: Only 50% of errors were related to the correct
      source population by more than 70% of OTs. CONCLUSION: Performance-based ADL
      assessments allowing for the documentation of context could enhance OTs'
      interpretation of ADL errors.

PMID- 17235229
TI  - Measuring perceived communicative ability after traumatic brain injury:
      reliability and validity of the La Trobe Communication Questionnaire.
AB  - OBJECTIVE: Further psychometric evaluation of a measure designed to assess
      communication ability after traumatic brain injury (TBI). DESIGN: Internal
      consistency, test-retest reliability, and validity for self-report and close
      other versions of the tool were evaluated. PARTICIPANTS: Eighty-eight adults with
      severe TBI (mean posttraumatic amnesia 53.12 days) and 71 close others (relatives
      or friends). MEASURE: The La Trobe Communication Questionnaire (LCQ), a 30-item
      questionnaire that measures cognitive-communication ability from multiple
      perspectives. RESULTS: Internal consistency coefficients were above 0.9 and test
      retest reliability exceeded 0.80. The questionnaire was sensitive to the effect
      of severity of injury. CONCLUSION: The La Trobe Communication Questionnaire is a
      promising tool for measuring perceived communication ability in adults with
      severe TBI.

PMID- 17235230
TI  - Psychotherapy following traumatic brain injury: integrating theory and practice.
AB  - Psychotherapy is now an approach used within several models of
      neurorehabilitation. However, a core theoretical model to guide psychotherapeutic
      practice is lacking. This article attempts to illustrate how the Generic Model of
      Psychotherapy of Orlinsky and Howard, which emphasizes the common factors shared
      by many psychotherapies, can be applied in neurorehabilitation settings. A case
      report is presented to illustrate how this model can potentially inform
      psychotherapeutic practice. The use of a theoretical model to underpin
      psychotherapeutic interventions in neurorehabilitation settings has the potential
      to facilitate our understanding of the psychotherapeutic process following
      traumatic brain injury in this evolving area of professional practice.

PMID- 17235231
TI  - Models of exceptional adaptation in recovery after traumatic brain injury: a case
      series.
AB  - OBJECTIVE: The remarkable persistence of disablement in chronic traumatic brain
      injury and the dearth of accommodation define the condition as a disorder of
      adaptation. This construct is extended to explain exceptional recoveries after
      postacute treatment. METHOD: Nine severely injured graduates of holistic
      cognitive rehabilitation were selected for their exceptional postmorbid academic,
      vocational, and social accomplishments. RESULTS: In interviews, they attributed
      their successes to continuing reliance on, and ongoing elaboration and
      modification of, cognitive compensation strategies. Unlike their disabled
      cohorts, they implement a deliberate procedure for self-corrective self
      management that minimizes the functional impact of their permanent deficits.

PMID- 17235233
TI  - Pharmacotherapy of aphasia.

PMID- 17235232
TI  - The long-term impact and rehabilitation of pediatric traumatic brain injury: a 50
      year follow-up case study.
AB  - Despite significant advances in the understanding of pediatric traumatic brain
      injury (TBI)-related sequelae, members of the medical community working with
      adult survivors often do not appreciate the impact of "latent" effects of these
      injuries. To assess deficits and facilitate intervention, the interactions among
      the nature of the TBI, the individual's developmental course, and the history of
      community response must be understood. This case study discusses the lifelong
      challenges faced by a 56-year-old individual who sustained a TBI at age 5. His
      case highlights the importance of developmental stage consideration, remote
      evaluation/intervention, and collaboration with mental health professionals.

PMID- 17235234
TI  - Pharmacological treatment of insomnia for individuals with brain injury.

PMID- 17235236
TI  - The involvement of apoptosis in melanoma vasculogenic mimicry.
AB  - During development, the formation and remodeling of the primary vascular network
      occurs by vasculogenesis and angiogenesis. In 1999, the concept of vasculogenic
      mimicry was introduced to describe the unique ability of highly aggressive tumor
      cells to form a capillary-like structure and a matrix-rich patterned network in
      three-dimensional culture that mimic the embryonic vasculogenic network. In this
      study, we examined the ability of melanoma cells derived from patients with
      disseminated melanoma to engage in vasculogenic mimicry in order to identify key
      parameters in the complexity of the formation of capillary-like structure. We
      showed that disseminated melanoma as well as uveal and cutaneous melanoma adopts
      a vascular-related phenotype and engages in vasculogenic mimicry: the main
      geometrical features of capillary-like structure are determined during the first
      step of the vascular network assembly. We provided experimental evidence that
      capillary-like structure formation requires apoptotic cell death through
      activation of a caspase-dependent mechanism: a broad range caspase inhibitor zVAD
      fmk and a caspase-3 inhibitor DEVD blocked capillary-like structure formation.
      Apoptosis occurs before capillary-like structure formation but not after
      capillary-like structures have assembled. These observations may provide a better
      understanding of the mechanisms involved in melanoma vasculogenic mimicry.

PMID- 17235237
TI  - Beta1,6-branched oligosaccharides regulate melanin content and motility in
      macrophage-melanoma fusion hybrids.
AB  - In previous studies, fusion of peritoneal macrophages or blood monocytes with
      mouse melanoma cells produced hybrids with upregulated expression of the
      glycosyltransferase beta1,6-N-acetylglucosaminyltransferase V (GnT-V) and its
      enzymatic product, beta1,6-branched oligosaccharides. This correlated with marked
      increases in motility, metastatic potential and, surprisingly, melanin content.
      This study was designed to establish direct roles for beta1,6-branched
      oligosaccharides in melanogenesis and motility. The levels of beta1,6-branched
      oligosaccharides were lowered by transfecting beta1,4-N
      acetylglucosaminyltransferase III, a competitive inhibitor of GnT-V. beta1,4-N
      acetylglucosaminyltransferase III transfection virtually eliminated melanin
      production and markedly decreased chemotactic motility. This implied that the
      metastatic and melanogenic phenotypes in hybrids were each upregulated by beta1,6
      branched oligosaccharides. Although roles for beta1,6-branched oligosaccharides
      in motility and metastasis have been reported previously, this is the first study
      to directly implicate these structures in melanogenesis. Although drawn from
      experimental models, the findings might explain the well known hypermelanotic
      regions of human cutaneous malignant melanoma as hypermelanotic cutaneous
      malignant melanoma cells are rich in beta1,6-branched oligosaccharides. They
      might also explain why melanogenesis pathways differ between malignant and normal
      melanocytes as GnT-V is a myeloid-associated enzyme that is aberrantly expressed
      in melanoma cells but not in normal melanocytes.

PMID- 17235238
TI  - Non-malignant migration of B16 mouse melanoma cells in the neural crest and
      invasive growth in the eye cup of the chick embryo.
AB  - Melanocytes originate from the neural crest. In a previous study, we observed
      that human SK-Mel 28 human melanoma cells resumed neural crest cell migration
      after transplantation into the chick embryo neural tube. Here, we used transgenic
      mouse B16-F1 melanoma cells transfected with green fluorescent protein
      vasodilator-stimulated phosphoprotein construct to extend these observations.
      After the injection of a cell suspension into the trunk neural tube of E2 chick
      embryos, the migration of melanoma cells was followed by live fluorescence
      microscopy. Within 12 h, the melanoma cells formed clusters in the neural tube at
      the levels of the intersegmental clefts between somites. After 24 h, a segmental
      pattern of emigration was visible. Emigrated melanoma cells were identified in
      serial paraffin sections by immunohistochemistry with ab732 as a marker for
      melanoma cells and by in-situ hybridization of mouse-specific repetitive genomic
      sequence mL1. After 24 h, melanoma cells were found along the medial neural crest
      pathway and in the sympathetic trunk ganglia and, after 48 h, also in the lateral
      melanocytic pathway. During migration along the neural crest pathways, mouse
      melanoma cells underwent apoptosis, which was assessed by anti-caspase 3 and
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin
      nick-end labeling staining. To prove the ablation of malignant behavior after
      back-transplantation into the original embryonic neural crest environment, we
      injected the same cell suspension into the eye cup of the E3 embryo. In this
      location, invasive melanomas formed.

PMID- 17235239
TI  - Birth outcome in Danish women with cutaneous malignant melanoma.
AB  - Several factors may affect birth outcome in women with cutaneous malignant
      melanoma. We examined whether maternal cutaneous malignant melanoma affects birth
      outcome (preterm birth, low birth weight at term, stillbirth, congenital
      abnormalities, mean birth weight, and male proportion of newborns) in a
      nationwide cohort study of 1059 births from 1973 to 2002 to women with cutaneous
      melanoma, compared with 50,794 births from a cohort of mothers without cancer. We
      found no increased risk of adverse birth outcome for the 620 newborns born to
      women with a diagnosis of melanoma before pregnancy or the 88 newborns born to
      women diagnosed during pregnancy. Among 351 births of women diagnosed with
      melanoma within 2 years from the time of delivery, the prevalence odds ratio of
      stillbirth was 4.6 (95% confidence interval: 1.7; 12). This estimate was,
      however, based on only five stillbirths in the exposed group and was an
      unexpected finding. With this exception, our data suggest no substantially
      increased risk of adverse birth outcome for women with melanoma.

PMID- 17235240
TI  - Gene-specific fluorescence in-situ hybridization analysis on tissue microarray to
      refine the region of chromosome 20q amplification in melanoma.
AB  - Several comparative genomic hybridization studies provide evidence for
      overrepresentation of the long arm of chromosome 20 in malignant melanoma. These
      studies also suggest that chromosome 20q contains genes that may contribute to
      melanoma pathogenesis. To refine the region of 20q amplification and to identify
      potential candidate genes involved in melanoma or even in melanoma progression
      from these regions, we combined fluorescence in-situ hybridization with MYBL2,
      ZNF217, CYP24 and STK6 specific probes (chromosomal region 20q13.1-q13.2) with
      high-throughput tissue microarray consisting of 280 primary melanomas and
      melanoma metastases. Low-level amplification ranging from 0.5 to 2.0% was
      detected for the tumor-related genes of interest. Higher frequencies of gain when
      compared with amplification were detected for MYBL2, ZNF217, CYP24 and STK6.
      Aneusomy of centromere 20 was observed in 29.9% of the analyzed tumors. A
      significantly higher frequency of ZNF217, CYP24 and STK6 total copy-number
      increase, as well as aneusomy of centromere 20, was found in the group of
      metastases when compared with the group of primary melanomas. Despite the
      technological advantage of fluorescence in-situ hybridization on tissue
      microarray, which allows refining regions of amplification, we were not able to
      recognize any of the MYBL2, ZNF217, CYP24 and STK6 genes as a particular relevant
      gene for melanoma tumorigenesis.

PMID- 17235241
TI  - Development and characteristics of a human cell assay for screening agents for
      melanoma prevention.
AB  - This paper describes the development and initial evaluation of a human cell assay
      to identify potentially efficacious agents for preventing melanoma. Four human
      cell lines were used: normal melanocytes, a radial growth-phase-like melanoma
      cell line (WM3211), a vertical growth-phase-like melanoma cell line (Lu1205), and
      83-2c, a cell strain cloned from metastatic melanoma. Four endpoints were
      evaluated in ultraviolet B-treated cells: annexin V, human leukocyte antigen-DR;
      E-cadherin, and N-cadherin. Annexin V was induced by nimesulide, 4
      hydroxyphenylretinamide, and difluoromethylornithine in ultraviolet-B-treated
      radial growth-phase-like melanoma cells. None of the agents inhibited human
      leukocyte antigen-DR expression in ultraviolet-B-treated radial growth-phase-like
      melanoma cells, the only cells that strongly expressed human leukocyte antigen
      DR. E-cadherin was overexpressed only in radial growth-phase-like melanoma cells
      relative to melanocytes, and ultraviolet B exposure dramatically reduced this
      expression. E-cadherin was only induced by difluoromethylornithine in ultraviolet
      B-treated radial growth-phase-like melanoma cells. N-cadherin was over- expressed
      in all melanoma cell lines relative to melanocytes. In this study, all candidate
      preventive agents inhibited N-cadherin in ultraviolet B-treated radial growth
      phase-like melanoma cells. Four agents inhibited N-cadherin in ultraviolet B
      treated vertical growth-phase-like melanoma cells. The mean ratios of N-cadherin
      to E-cadherin levels and specific endpoint responses for both the radial growth
      phase-like melanoma and vertical growth-phase-like melanoma cells were used to
      rank the agents. Agents were evaluated at clinically relevant concentrations. The
      rankings were difluoromethylornithine>4-hydroxyphenylretinamide>nimesulide>9-cis
      retinoic acid>polyphenon E. Diphenylhydramine, D-mannitol, and
      nordihydroguaiaretic acid were inactive. The results of these initial studies
      suggest that ultraviolet-B-treated radial growth-phase-like melanoma cells are
      the most responsive to chemopreventive agents, and may be the cell line of choice
      for screening melanoma prevention agents.

PMID- 17235242
TI  - Sun-related behavior after a diagnosis of cutaneous malignant melanoma.
AB  - Cutaneous malignant melanoma is a significant public health problem in Western
      countries, and the probability that patients with one melanoma will develop a
      second one is high. This study is an attempt to assess and understand sun-related
      behavior in patients subsequent to a melanoma diagnosis. We recruited 35 melanoma
      patients diagnosed in 2001 or 2002, who resided in the Greater Vancouver Regional
      District of British Columbia, Canada, and 35 controls frequency matched by broad
      age-group, sex, ethnicity, and area of residence to patients. All participants
      were interviewed over the telephone in the autumn of 2003 to ascertain their
      outdoor activities for the previous summer months (June-August) of 2003, along
      with their clothing preferences, sunscreen use, sunburn frequency, and knowledge
      and attitudes regarding sun exposure and tanning. Patients were less involved in
      outdoor recreational activities than controls (mean monthly hours 23.0 vs. 31.0,
      P=0.023). In addition, patients protected themselves from sun exposure using
      clothing and sunscreen more often than controls. However, the data also revealed
      that patients still engaged in outdoor activities to a substantial degree, often
      without sun protection. Furthermore, 27% still had a positive or neutral attitude
      toward tanning, even after melanoma diagnosis. The continuing presence of
      unprotected episodes of summer sun exposure in patients with melanoma, coupled
      with sunburn prevalence similar to normal controls, suggests that better
      education and behavior modification programs are needed for patients with
      melanoma. The results may indicate the need for more emphasis on post-treatment
      counseling by physicians.

PMID- 17235243
TI  - Interferon therapy discussed at the Sixth International Conference on the
      Adjuvant Therapy of Malignant Melanoma, Stockholm, Sweden, 15-17 June 2006.

PMID- 17235244
TI  - Sentinel lymph node biopsy: a new perspective in head and neck mucosal melanoma?

PMID- 17235246
TI  - The health care quality journey of Jonkoping County Council, Sweden.
AB  - For a decade Jonkoping County Council in Sweden has undertaken a countywide
      effort to improve health and health care with measured success. This issue
      describes this quality improvement journey.

PMID- 17235247
TI  - Making systemwide improvements in health care: Lessons from Jonkoping County,
      Sweden.
AB  - Over the past 10 years, Jonkoping County in Sweden has made impressive progress
      in improving its health care system. The motor of improvement work is Qulturum,
      an innovation and learning center within the health system. Qulturum has no
      responsibilities for clinical or administrative functions; its sole mission is
      improvement work. Qulturum's improvement strategy is based on 3 principles: (1)
      Learning is key to improvement, (2) Improvement needs to be broad and deep, and
      (3) Improvement must be both bottom-up and top-down. Based on these principles,
      Jonkoping County has achieved timely access to primary and specialty care, has
      improved the care of a number of chronic conditions, and has accomplished these
      goals without increases in expenditures. The United States could benefit by
      instituting Qulturum-like centers of learning and innovation within health
      systems.

PMID- 17235248
TI  - How improved access to healthcare was successfully spread across Sweden.
AB  - BACKGROUND: Swedish healthcare has an internationally high standard, but is often
      criticized from a patient perspective owing to access problems to primary and
      specialist care. The waiting time to get in touch or get an appointment with a
      doctor, nurse, or physiotherapist is often too long. Access problems also create
      stress for employees when there are too few appointments to offer. In addition,
      too much time gets spent on the administration of long waiting lists, which adds
      no value to patients. Jonkoping County Council was not satisfied with this
      situation and decided to make an attempt to improve access in the whole system.
      PURPOSE: To describe how access was improved in Jonkoping County council and how
      the concept was spread nationally. METHOD: A conceptual model for improved access
      and reduced queues in Jonkoping County called Bra Mottagning (BM) ("Good Clinic"
      in Swedish) was developed in 1999. It was built on logistic principles and
      collaborative learning. The program consisted of 4 learning sessions over a
      period of 8 to 9 months. The process of learning, team development, leadership,
      and spread of a change concept for improved access in Sweden has evolved through
      repeated improvement cycles, from small tests to larger pilots and finally to a
      standardized concept. RESULTS: Since 1999, 2 new BM collaboratives have been
      started every year. The first 11 teams from the county council of Jonkoping,
      which participated in BM1 to BM3, reduced their median waiting time from 90 to 7
      days in 8 months, an improvement of 93% (83 days). The results have been
      sustainable over the last 7 years. In the county council as a system, advanced
      access was achieved in 40% of the 179 units in 2006. Since the national spread
      started, 2200 employees in 316 professional teams from 16 county councils in
      Sweden have participated in BM collaboratives. Of these, 80% improved access for
      their patients and 32% reached advanced access in 8 months. CONCLUSION: The
      described development and spread of a concept for improved access in Sweden has
      been successful. A general impression is that the spread was more successful in
      the counties where the top management was strongly committed to the mission and
      the concept. Important factors for the national spread have been the
      establishment of a broader planning group as a network, the education of access
      coaches, the standardization of methods, and scientific assessments of the
      concept. Our experience is that both leaders and employees need to share a
      holistic view and systems thinking and also develop a deep interest in learning
      about strategies for access improvement.

PMID- 17235249
TI  - Improving guideline adherence through intensive quality improvement and the use
      of a National Quality Register in Sweden for acute myocardial infarction.
AB  - OBJECTIVE: Data from the Swedish National Register in Cardiac Care have shown
      over the last 10 years an enduring gap between optimal treatment of acute
      myocardial infarction (AMI) according to current guidelines and the treatment
      actually given. We performed a controlled, prospective study in order to evaluate
      the effects of applying a multidisciplinary team-based improvement methodology to
      the use of evidence-based treatments in AMI, together with the use of a modified
      National Quality Register. The project engaged 25% of the Swedish hospitals.
      METHOD: Multidisciplinary teams from 20 hospitals participating in the National
      Register in Cardiac Care, ranging from small to large hospitals, were trained in
      continuous quality improvement methodology. Twenty matched hospitals served as
      controls. Our efforts were focused on finding and applying tools and methods to
      increase adherence to the national guidelines for 5 different treatments for AMI.
      For measurement, specially designed quality control charts were made available in
      the National Register for Cardiac Care. RESULTS: To close the gap, an important
      issue for the teams was to get all 5 treatments in place. Ten of the hospitals in
      the study group reduced the gap in 5 of 5 treatments by 50%, while none of the
      control hospitals did so. CONCLUSIONS: This first, controlled prospective study
      of a registry supported by multidisciplinary team-based improvement methodology
      showed that this approach led to rapidly improved adherence to AMI guidelines in
      a broad spectrum of hospitals and that National Quality Registers can be helpful
      tools.

PMID- 17235250
TI  - Improved population-based care: Implementing patient-and demand-directed care for
      inflammatory bowel disease and evaluating the redesign with a population-based
      registry.
AB  - The gastroenterology unit at the Hoglands Hospital in Eksjo is responsible for
      the care of all 466 patients with inflammatory bowel disease (IBD) in a
      geographic area including approximately 115,000 inhabitants. In 2000, the
      frustration over an inadequate traditional outpatient clinic inspired us to
      redesign our outpatient unit to become more patient and demand directed. The
      redesign included the following: A direct telephone line for patients to a
      specialized nurse, available during working hours; appointments were scheduled in
      accordance with expected needs, and emergency appointments were available daily;
      traditional follow-ups of IBD patients were replaced by an annual telephone
      contact with a specialized nurse; the team agreed on a patient-centered value
      base for its work, and the redesign was monitored using clinical outcome measures
      reflecting 4 dimensions (see parentheses below) of the care in a "Value compass";
      quality of life (functional) and routine blood samples (clinical) were followed
      yearly and collected in a computerized IBD registry together with basic
      information about the patients; access and waiting lists together with patient
      satisfaction (satisfaction) are followed regularly; and ward utilization
      (financial) was registered. Our study shows that the new design offers a more
      efficient outpatient clinic in which waiting lists are markedly reduced although
      production rates remains the same. Utilization data show a significant decrease
      in comparison with national data, showing that the new care is economically
      favorable. The clinical results regarding anemia frequency in the IBD population
      are highly comparable with or even better than those found in the literature. We
      also show good results regarding quality of life where more than 88% of patients
      achieve set goals. In conclusion, our new patient- and demand-directed care seems
      to be more efficient and with clinical and quality-of-life results remaining on a
      high standard.

PMID- 17235251
TI  - The rate of influenza immunization to people aged 65 years and older was
      increased from 45% to 70% by a primary health care-based multiprofessional
      approach.
AB  - For many years, Swedish health authorities have recommended yearly influenza
      immunization to persons in medical risk groups and to people aged 65 years and
      older. Despite this recommendation, the vaccination coverage has been lower than
      50% in Jonkoping County, as in all other counties of Sweden. To increase the rate
      of influenza immunization in Jonkoping County, we established a multiprofessional
      action group and designed a primary health care-based program. Important elements
      in the project were free of charge vaccination; an education program targeting
      primary health nurses; mass media information through advertisements in
      newspapers, local TV, posters, and handouts; and instituting and implementing a
      computerized registry with easy access to summary statistics by which each unit
      could compare its achievements with others. Personal invitation letters were not
      used because of economical reasons. The vaccination was performed in the county's
      health centers and to lesser extent in the hospitals. Most of the health centers
      are owned and run by the county council. A few health centers are private but
      have contract with the county council. Economical incentives to the providers
      were not used. During a 4-year period, the immunization rate among all
      inhabitants of the county aged 65 years increased from 45% to 70%. All the 13
      municipalities in the county increased their vaccination rate; their recent
      figures vary between 61% and 74%. The vaccination rate among people aged 65 years
      in Jonkoping County is now the highest in Sweden, but still not as high as in
      some other European countries. Our influenza immunization campaign can act as an
      example for other healthcare providers.

PMID- 17235252
TI  - Reduction of antibiotics sales and sustained low incidence of bacterial
      resistance: Report on a broad approach during 10 years to implement evidence
      based indications for antibiotic prescribing in Jonkoping County, Sweden.
AB  - BACKGROUND: Increased prevalence of resistance in major pathogens decreases the
      possibility to treat common infectious conditions. In the beginning of the 1990s,
      resistant pneumococci spread among children in southern Sweden, which alarmed
      both the profession and the medical authorities. We describe the measures taken
      to curb the spread of resistance and to reduce the use of antibiotics in
      outpatient care. METHOD: A national organization, Strama (Swedish Strategic
      Programme for the Rational Use of Antimicrobial Agents and Surveillance of
      Resistance), was initiated in 1994 and a regional committee was formed in
      Jonkoping County in 1995. A multifaceted program was started aiming at reducing
      antibiotic use in the county by 25% and that the prevalence of resistant
      pneumococci should not increase. RESULTS: The efforts by the Jonkoping County
      committee has resulted in a 31% total reduction of the consumption of antibiotic
      drugs in primary care between 1993 and 2005 and a 50% reduction among children
      aged 0 to 4 years. There has been no increase in the prevalence of resistant
      pneumococci or Haemophilus influenzae in the county. The decrease in antibiotic
      use was greater than the average in Sweden. CONCLUSION: Our regional efforts have
      been successful. This has probably been achieved by a sustained strategy
      including repeated campaigns in the media, information to the profession,
      implementation of guidelines, and feedback to the profession on data on
      antibiotic prescribing and resistance. We believe it is of outmost importance not
      only to inform the profession but also the public on the limited effects of
      antibiotics in most respiratory tract infections.

PMID- 17235253
TI  - Sustained improvement? Findings from an independent case study of the Jonkoping
      quality program.
AB  - Quality methods of many types have been widely used in hospitals. Although a
      number of specific projects have shown evidence of improvement, there is no
      strong evidence of the effectiveness of organization-wide or system programs over
      a period of time. There is no evidence of which approaches might be more suitable
      for different settings, or of value for money compared, for example, to employing
      more doctors and nurses. Jonkoping is widely known in Sweden and internationally
      as one long-running example of a successful systemwide improvement program. As
      with other programs, critics and researchers have asked for evidence of improved
      outcomes for patients and of the costs of the program. There are methodological
      challenges to providing strong evidence of these outcomes, even in small projects
      where it is easier to attribute outcomes to interventions, at least over the
      short term. However, there are ways to gather data that are more objective than
      participants' and consultants' reports and that are useful for assessing the
      value of the program and to enable others to learn from the experience of
      Jonkoping. This article presents such data from a case study of the program
      carried out in 2006. It presents evidence of how the program was implemented, of
      some results, and of the unusual conditions that appear to have shaped or allowed
      the program to be carried out in the way described. There is some evidence of
      process improvements in a number of departments and of outcomes improvement in
      one department. The program is widely perceived to be of benefit and some of the
      explanations for this are presented.

PMID- 17235254
TI  - Goal orientation and conflicts: Motors of change in development projects in
      health care service.
AB  - In this article we present parts of a larger research study, which aims at
      explaining how a process-oriented innovation unfolds and develops over time in
      Swedish health care. Through a longitudinal field study of a national and a local
      development project, we analyze how the flow model--a process-oriented innovation
      that emphasizes the sequence of activities a patient undertakes through the
      health care system--has been developed in Swedish health care. We propose to
      explain how the development projects unfold over time through the use of process
      theories of organizational development and change. The national project is best
      understood as a process of evolution from the phase of selection of projects and
      teleological (goal-oriented, socially constructed development) and dialectic
      theory (development via conflict of 2 opposing ideas from different
      organizational entities) through the process in which national ideas face real
      world practice. We also propose a synthesis of dialectics and teleological motors
      for explaining local development. This synthesis proposes that local development
      teams have a rather broad notion of what it takes to implement the flow model.
      The team knows the goal, procedures, and activities from a broad perspective.
      Through a search-and-interact process, in which other organizational entities
      such as IT consultants, medical units and politicians have a heavy influence, the
      group sets and implements goals. Details of how to proceed are, however,
      constructed in the process of acting. This occurs as ideas are developed and
      tested in real settings. We conclude the article by presenting managerial
      implications for understanding these process patterns.

PMID- 17235257
TI  - Role of interleukin-8 and growth-regulated oncogene-alpha in the chemotactic
      migration of all-trans retinoic acid-treated promyelocytic leukemic cells toward
      alveolar epithelial cells.
AB  - OBJECTIVE: Although all-trans retinoic acid (ATRA) can treat acute promyelocytic
      leukemia (APL), it also causes retinoic acid syndrome with presentations similar
      to acute respiratory distress syndrome. We investigated the role of interleukin
      (IL)-8 and growth-regulated oncogene (GRO)-alpha in the chemotactic
      transmigration of ATRA-treated NB4 (ATRA-NB4) APL cells toward A549 alveolar
      epithelial cells. DESIGN: An in vitro human cell culture study. SETTING:
      University hospital research laboratories. SUBJECTS: NB4 and A549 cells.
      INTERVENTIONS: NB4 and A549 cells were separately cultured with ATRA and/or
      dexamethasone for 1-3 days. NB4 or ATRA-NB4 cells were then placed in an upper
      insert and co-incubated with A549 cells or their conditioned medium located in a
      lower plate. MEASUREMENTS AND MAIN RESULTS: ATRA stimulated NB4 cells to
      transmigrate toward the A549 cells in a time- and dose-dependent manner.
      Replacement of A459 condition medium by its original medium abrogated this
      transmigration. Only A549 cells constitutively secreted GRO-alpha, and both A549
      and NB4 cells constitutively secreted IL-8, which was enhanced by ATRA. Exogenous
      administration of IL-8 or GRO-alpha also promoted the ATRA-NB4 transmigration.
      The binding assay demonstrated that ATRA-NB4 cells bound IL-8, but not GRO-alpha,
      more avidly. Pretreatment with antibodies directed against IL-8 and GRO-alpha
      receptors reduced ATRA-NB4 transmigration by about 60%. Dexamethasone did not
      suppress their IL-8 secretion and transmigration in ATRA-NB4 cells, but when
      applied to A549 cells, IL-8 secretion was suppressed but not GRO-alpha secretion,
      and there was attenuation of ATRA-NB4 transmigration. CONCLUSIONS: IL-8 and GRO
      alpha secreted from alveolar epithelial cells play an important role in the cell
      cell interaction involved in the chemotactic transmigration of ATRA-treated APL
      cells toward alveolar epithelial cells.

PMID- 17235258
TI  - Practice guidelines as multipurpose tools: a qualitative study of noninvasive
      ventilation.
AB  - OBJECTIVE: Although practice guidelines for noninvasive ventilation (NIV) for
      patients with acute respiratory failure (ARF) have the potential to improve
      processes of care and patient outcomes, clinicians' views about life support
      technology guidelines are not well understood. The objective was to understand
      the knowledge about and attitudes toward an NIV guideline for patients with ARF
      and potential barriers to its use. DESIGN: Qualitative study based on individual,
      in-depth, semistructured interviews. SETTING: St. Joseph's Healthcare, Hamilton,
      Ontario. SUBJECTS: Thirty clinicians (six attending physicians, five residents,
      12 nurses, and seven respiratory therapists) who used NIV for chronic obstructive
      pulmonary disease and congestive heart failure patients with ARF, before and
      after NIV guideline implementation. INTERVENTIONS: We elicited knowledge and
      attitudes about, behaviors toward, and barriers to our institutional NIV
      guideline. We transcribed all interviews and analyzed data in triplicate using
      grounded theory to identify themes and develop a framework for understanding
      clinicians' views on guidelines. MEASUREMENTS AND MAIN RESULTS: The NIV guideline
      was perceived to define individual clinical responsibilities, improve clinician
      comfort with use of technology, increase patient safety, and reduce practice
      variability. Barriers to guideline use included lack of awareness of the
      guideline, unclear guideline format and presentation, and reluctance about
      changing practice. Contrary to previous research, participants in this study did
      not report that the practice guideline limited clinical autonomy. Clinicians used
      the guideline variously as an educational resource, to access monitored beds, to
      avoid clinical conflict, or to leverage professional credibility. CONCLUSIONS:
      This qualitative study illustrated how the NIV guideline at our institution is
      understood as a tool that facilitates the multidisciplinary care of patients with
      ARF. Guideline use may be enhanced through education to improve guideline
      awareness and increase comfort with recommended practices. Developers should be
      aware of the role of guidelines for purposes other than bedside decision making
      for individual patients.

PMID- 17235259
TI  - Inhibitor kappaB-alpha haplotype GTC is associated with susceptibility to acute
      respiratory distress syndrome in Caucasians.
AB  - OBJECTIVE: The nuclear factor (NF)-kappaB regulates inflammatory responses and
      plays important roles in the pathogenesis of acute respiratory distress syndrome
      (ARDS). Inhibitor kappaB-alpha (NFKBIA) inhibits NF-kappaB and controls its
      activities. The objective was to determine whether polymorphisms in NFKBIA gene
      would be associated with ARDS development. DESIGN: Prospective cohort of adults
      with clinical risk factors for ARDS. SETTING: Hospital system. PATIENTS: Patients
      were 1,210 critically ill Caucasian patients meeting study criteria for a defined
      risk factor for ARDS who were enrolled and prospectively followed for 60 days;
      382 had ARDS, and 828 were controls. INTERVENTIONS: Genetic polymorphisms in the
      NFKBIA promoter (-881A/G, -826C/T, -297C/T) were determined using TaqMan
      techniques. MEASUREMENTS AND MAIN RESULTS: The three polymorphisms were in Hardy
      Weinberg equilibrium. No individual genotype was significantly associated with
      ARDS development. In contrast, haplotypes of NFKBIA were globally associated with
      ARDS development (p = .02, degree of freedom = 2). The frequency of haplotype GTC
      (-881G/-826T/-297C) was significantly higher among ARDS patients (7.4%) than that
      among controls (5.2%) (p = .03). Crude analysis showed that the haplotype GTC was
      significantly associated with higher risks of ARDS in the whole cohort compared
      with the common haplotype ACC (-881A/-826C/-297C) (odds ratio [OR], 1.47; 95%
      confidence interval [CI], 1.03-2.09; p = .03), especially among male subjects
      (OR, 1.90; 95% CI, 1.20-2.97; p < .01). After adjustment for covariates, the
      haplotype GTC remained significantly associated with increased risk of ARDS in
      the whole cohort (OR, 1.66; 95% CI, 1.09-2.53; p = .02), particularly among male
      patients (OR, 1.98; 95% CI, 1.16-3.40; p = .02) and among subjects with direct
      pulmonary injury (OR, 1.75; 95% CI, 1.04-2.95; p = .04). CONCLUSIONS: The
      haplotype GTC of NFKBIA gene is associated with higher risk of ARDS in
      Caucasians, particularly in male patients and in patients with direct lung
      injury.

PMID- 17235260
TI  - Evaluating the management of septic shock using patient simulation.
AB  - OBJECTIVE: Develop a scoring system that can assess the management of septic
      shock by individuals and teams. DESIGN: Retrospective review of videotapes of
      critical care house staff managing a standardized simulation of septic shock.
      SETTING: Academic medical center; videotapes were made in a recreated intensive
      care unit environment using a high-fidelity patient simulator. SUBJECTS:
      Residents in medicine, surgery, and anesthesiology who had participated in the
      intensive care unit rotation. INTERVENTIONS: The septic patient was managed by
      the intensive care unit team in a graded manner with interns present for the
      first 10 mins and more senior-level help arriving after 10 mins. The intern was
      graded separately for the first 10 mins, and the team was graded for the entire
      35-min performance. MEASUREMENTS AND MAIN RESULTS: Both technical and
      nontechnical scoring systems were developed to rate the management of septic
      shock. Technical scores are based on guidelines and principles of managing septic
      shock. Team leadership, communication, contingency planning, and resource
      utilization were addressed by the nontechnical rating. Technical scores were
      calculated for both interns and teams; nontechnical scores applied only to the
      team. Of 16 technical checklist items, interns completed a mean of 7 with a range
      of 1.5-11. Team technical ratings had a mean of 9.3 with a range of 3.3-13.
      Nontechnical scores showed similar intergroup variability with a mean of 26 and a
      range of 10-35. Technical and nontechnical scores showed a modest correlation (r
      = .40, p = .05). Interrater reliabilities for intern and team technical scores
      were both r = .96 and for nontechnical scores r = .88. CONCLUSIONS: Objective
      measures of both knowledge-based and behavioral skills pertinent to the
      management of septic shock were made. Scores identified both adequate and poor
      levels of performance. Such assessments can be used to benchmark clinical skills
      of individuals and groups over time and may allow the identification of
      interventions that improve clinical effectiveness in sepsis management.

PMID- 17235261
TI  - The ICU trial: a new admission policy for cancer patients requiring mechanical
      ventilation.
AB  - OBJECTIVE: Cancer patients requiring mechanical ventilation are widely viewed as
      poor candidates for intensive care unit (ICU) admission. We designed a
      prospective study evaluating a new admission policy titled The ICU Trial. DESIGN:
      Prospective study. SETTING: Intensive care unit. PATIENTS: One hundred eighty
      eight patients requiring mechanical ventilation and having at least one other
      organ failure. INTERVENTIONS: Over a 3-yr period, all patients with hematologic
      malignancies or solid tumors proposed for ICU admission underwent a triage
      procedure. Bedridden patients and patients in whom palliative care was the only
      cancer treatment option were not admitted to the ICU. Patients at earliest phase
      of the malignancy (diagnosis < 30 days) were admitted without any restriction.
      All other patients were prospectively included in The ICU Trial, consisting of a
      full-code ICU admission followed by reappraisal of the level of care on day 5.
      MEASUREMENTS AND MAIN RESULTS: Among the 188 patients, 103 survived the first 4
      ICU days and 85 died from the acute illness. Hospital survival was 21.8% overall.
      Among the 103 survivors on day 5, none of the characteristics of the malignancy
      were significantly different between the 62 patients who died and the 41 who
      survived. Time course of organ dysfunction over the first 6 ICU days differed
      significantly between survivors and nonsurvivors. Organ failure scores were more
      accurate on day 6 than at admission or on day 3 for predicting survival. All
      patients who required initiation of mechanical ventilation, vasopressors, or
      dialysis after 3 days in the ICU died. CONCLUSIONS: Survival was 40% in
      mechanically ventilated cancer patients who survived to day 5 and 21.8% overall.
      If these results are confirmed in future interventional studies, we recommend ICU
      admission with full-code management followed by reappraisal on day 6 in all
      nonbedridden cancer patients for whom lifespan-extending cancer treatment is
      available.

PMID- 17235262
TI  - White book on physical and rehabilitation medicine in Europe.

PMID- 17235263
TI  - End-of-life care and the intensivist: SIAARTI recommendations on the management
      of the dying patient.

PMID- 17235264
TI  - Postoperative myocardial infarction: pathophysiology, new diagnostic criteria,
      prevention.
AB  - With the introduction of biomarkers like troponin I (cTnI), our ability to
      identify and quantify myocardial infarction in the postoperative period has been
      greatly enhanced. Even small elevations of cTnI should be considered as a
      myocardial infarction. Small increases in cTnI postoperatively have indeed been
      found to be associated with worse short and long-term outcomes, the higher the
      cTnI level the worse the outcome. Studies undertaken in the 1980s when
      postoperative myocardial infarction (PMI) was detected by means of
      electrocardiogram recordings every 12 hours following operation suggested that
      this complication occurred on the second or third postoperative day. More recent
      studies where postoperative myocardial necrosis has been detected by repeated
      troponin dosages have revealed that, in fact, postoperative myocardial infarction
      appears much earlier between 12 and 32 hour after the end of surgery. Two types
      of PMI were identified based on intense troponin surveillance. They stem from two
      different major pathophysiological mechanisms. One seems to be related to plaque
      vulnerability, while the other may be due to the effects of prolonged ischemia.
      The postoperative period should be regarded as a vulnerable period' that acts
      synergistically with both plaque and patient vulnerabilities in the development
      of PMI. Monitoring troponin levels in the postoperative period following surgery
      enables the identification of patients with myocardial damage and the institution
      of early aggressive intervention (e.g., intensive beta blockers therapy, adequate
      analgesia, correction of anemia) in order to prevent the evolution of PMI during
      this golden period' that lasts about two days. In patients that are prone to
      develop PMI, and especially in those who are prone to develop PMI related to
      plaque rupture, prevention can be achieved by better preoperative identification
      of the vulnerable plaque, and by a better plaque stabilization, either
      metabolically (e.g., statins) or by actual coronary stenting. Further
      understanding of the mechanisms underlying PMI, as well as their early
      identification, may contribute to the reduction of the incidence of PMI and its
      associated morality in the future.

PMID- 17235265
TI  - Redo coronary artery bypass grafting on the beating heart and transfusion needs.
AB  - AIM: Reoperative coronary artery bypass grafting is associated with significant
      morbidity and a difficult perioperative management; in particular, important
      bleeding is observed. Off pump technique may give specific advantages in redo
      coronary operations since it is associated to decreased interactions of blood
      with foreign surfaces. We investigated our 5-year database to evaluate the role
      of off pump technique in reducing transfusion needs. METHODS: The present single
      centre case control study was carried out in a university tertiary care hospital
      on 132 consecutive patients undergoing reoperative coronary artery bypass
      grafting off pump (OP group, 41 patients) or with cardiopulmonary bypass (CPB
      group, 91 patients). Univariate and multivariate analysis were performed.
      RESULTS: There was no preoperative difference between the 2 groups; mean number
      of grafts per patient differed between groups (OP: 1.4+/-0.7, CPB: 2.5+/-1.0).
      The frequency of patients transfused with blood products was significantly
      (P=0.004) higher in the CPB group (47.3%) than in the OP group (19.5%). The only
      independent predictors of transfusions, determined by stepwise multivariate
      logistic regression analysis, was the use of cardiopulmonary bypass (OR: 4.1, CI:
      1.6 - 10.1), and female gender (OR: 7.0, CI: 2.1 - 16.1). CONCLUSION: In our
      centre, off pump coronary surgery is associated with reduced transfusion of blood
      products.

PMID- 17235266
TI  - Airway obstruction during arthroscopic shoulder surgery: anesthesia for the
      patient or for the surgeon?
AB  - Two cases of airway obstruction as a result of oedema of laryngeal structures
      which arose during protracted arthroscopic shoulder surgery, in which single-shot
      interscalene blocks had been performed, are reported. In these 2 cases, the
      complexity of the pathologies and the fact that the surgeons were at the
      beginning of their surgical experience are the most likely causes of the
      conditions which led to tracheal compression from extra-articular leakage of
      fluid. Therefore, we recommend a combined peripheral block and general
      anaesthesia with tracheal intubation for procedures performed by surgeons without
      an adequate experience and on obese patients, patients placed in a lateral
      decubitus, or procedures in which difficulties are expected. The advantages of
      regional anaesthesia with a constant control of the airways are underlined.

PMID- 17235267
TI  - Multivessel off-pump coronary artery bypass grafting in a nonagenarian:
      anesthesiologic management.
AB  - A 90-year-old male admitted with history of angina (three-vessel disease) on
      medical therapy for hypertension and chronic renal failure was scheduled for
      elective coronary artery bypass grafting (CABG). After standard premedication and
      monitoring anesthesia was induced with propofol and maintained with isoflurane.
      Middle dose opioids and atracurium were also given. Multivessel revascularization
      was done through median sternotomy and anastomoses were performed with the aid of
      coronary stabilization and shunting. Cerebral and renal perfusion were maintained
      with high arterial pressure (140/70 mmHg) and continuous infusion of fenoldopam
      (0.05 microg kg(1) m(-1)). The perioperative period was uneventful. Elderly
      patients are at increased risk for mortality and morbidity after CABG. The
      procedure can be performed safely on elderly patients without using
      cardiopulmonary bypass and preventing cerebral and renal ipoperfusion.

PMID- 17235268
TI  - Tracheal rupture after tracheal intubation: effectiveness of conservative
      treatment.
AB  - A tracheal rupture is a rare complication of tracheal intubation. Risk factors
      include advanced age, COBP and corticosteroid therapy. The direct causes of the
      rupture are difficult tracheal intubation, particularly with a stylet inside the
      tube and overdistension of the cuff of the tracheal tube. The case of a 73-year
      old woman with a tracheal rupture after an uncomplicated operation of a vaginal
      hysterectomy and bilateral adenexectomy is reported. The procedure of orotracheal
      intubation presented no difficulties. However, after 5 h the patient was
      presenting unexpected symptoms such as dyspnea and subcutaneous emphysema. After
      an inconclusive chest X-ray and chest TC, the diagnosis was made by emergency
      fiberendoscopy. We adopted a conservative treatment, consisting of a tracheal
      intubation and chest drain, which resulted in a full recovery after 5 days of
      mechanical ventilation. The causes that could have provoked a tracheal laceration
      in our patient and the suggested therapies with preference for conservative
      treatment, are discussed. We recommend a tracheal tube cuff monitoring during
      surgery, to prevent fatal overinflation of the cuff, which is permeable to
      nitrous oxide.

PMID- 17235269
TI  - Comparison between local and general anaesthesia for carotid endarterectomy. A
      retrospective analysis.

PMID- 17235270
TI  - Update on Pediatric ALL.

PMID- 17235271
TI  - Current controversies in the management of pancreatic cancer.

PMID- 17235272
TI  - CALGB 90202.

PMID- 17235273
TI  - Two new indications for rituximab.

PMID- 17235274
TI  - Imaging in drug development.

PMID- 17235275
TI  - Hematologic manifestations and diagnosis of parvovirus B19 infections.

PMID- 17235276
TI  - Rapid molecular diagnosis of a disseminated fungal infection presenting as sudden
      bilateral visual loss in a patient with acute myeloid leukemia.

PMID- 17235277
TI  - The pathogenesis and management of disseminated intravascular coagulation.
AB  - The pathologic and progressive generation of thrombin in human blood can result
      in the development of disseminated intravascular coagulation (DIC), a syndrome
      associated with many underlying conditions and manifested as microvascular
      thrombosis, tissue hypoxia, and organ damage. DIC can be either acute or chronic,
      with acute DIC resulting from generation of a large amount of thrombin in a brief
      time period and chronic (compensated) DIC developing as a result of exposure of
      the coagulation system to small amounts of tissue factor leading to increased but
      nonacute levels of thrombin generation. DIC can also be considered a
      thrombohemorrhagic syndrome. Acute DIC at first manifests in a hypercoagulable
      state and leads to thrombosis, but can be followed by the development of a so
      called hypocoagulable phase caused by depletion of clotting factors. This
      depletion can sometimes lead to bleeding. Bleeding is less common in chronic DIC,
      as coagulation factors and platelets are more likely to be able to be replenished
      in the majority of patients. Diagnosis of DIC can sometimes be difficult,
      depending upon the stage and presentation of the syndrome. During the thrombotic
      phase of DIC, many common laboratory parameters remain normal, with the important
      exception of an early drop in circulating platelets. DIC is easier to diagnose
      when the patient is bleeding, as abnormalities can normally be detected in global
      coagulation tests and factor assays. Therapy involves identification and
      treatment of the underlying condition, if possible. In the interim, measures to
      control bleeding can be administered, if necessary, and may include supportive
      care with blood products, antithrombin, heparin, and other agents.

PMID- 17235280
TI  - New paradigms in the management of hepatitis C virus co-infections.
AB  - Liver disease has emerged as a major contributor to morbidity and mortality in
      patients with HIV infection. Hepatitis C virus (HCV) infection is a key element
      in the etiology of liver-associated injury in this population. Increased rates of
      fibrotic progression have been described and are mediated by alcohol use, the
      severity of immunosuppression, the use of antiretroviral therapy, and other
      factors. Large clinical trials have demonstrated the efficacy of treatment with
      pegylated interferon plus ribavirin and highlighted issues related to management
      of patients with HIV/HCV co-infection. Although treatment for HCV infection in
      this group remains a challenge, achievement of a sustained virologic response is
      feasible in approximately 35% of patients. Treatment must be individualized and
      attention must be paid to the potential for drug-drug interactions.

PMID- 17235281
TI  - Emerging strategies for pegylated interferon combination therapy.
AB  - Several advances afford promise for improving the management of hepatitis C virus
      (HCV) infection. Current therapies primarily target the immune system; the now
      proven ability to culture the entire virus in vitro could ultimately facilitate
      the identification of therapies directly targeting viral replication. Several
      therapies are presently in development. Taribavirin hydrochloride (Viramidine,
      Valeant Pharmaceutical International, Singapore), a ribavirin prodrug, has shown
      promise, although the rate of sustained virologic response with this agent has
      been disappointing. The next generation of antivirals will consist of protease
      and polymerase inhibitors, a number of which are undergoing investigation,
      initially as monotherapy and subsequently in combination with pegylated
      interferon and ribavirin. Challenges include the prevention of recurrent HCV
      infection in liver-transplant recipients and development of a safe and effective
      HCV vaccine.

PMID- 17235282
TI  - Customizing treatment to patient populations.
AB  - Combination treatment with pegylated interferon plus ribavirin is the most
      effective therapy for patients with chronic hepatitis C virus (HCV); however,
      responses are less than optimal in some subpopulations of patients. Emerging
      insights are suggesting that viral kinetics can be used to predict response. The
      rapidity of response has been shown to be a more important predictor of sustained
      virologic response than the duration of therapy. In patients with HCV genotype 2
      or 3, shorter durations of treatment might be sufficient in rapid responders and
      could minimize the risk of toxic effects. Weight-based dosing of ribavirin has
      emerged as another important consideration. This strategy seems to be most
      important for difficult-to-treat patients with HCV genotype 1 or advanced
      fibrosis, and for African-Americans, and is possibly important for patients who
      have genotype 3 and a high viral load. Re-treatment of nonresponders with
      interferon-based therapy has been associated with low rates of sustained
      virologic response. Consensus interferon might offer a new option for patients
      who do not achieve an early treatment response to standard or pegylated
      interferon plus ribavirin.

PMID- 17235283
TI  - Efficient T-cell receptor signaling requires a high-affinity interaction between
      the Gads C-SH3 domain and the SLP-76 RxxK motif.
AB  - The relationship between the binding affinity and specificity of modular
      interaction domains is potentially important in determining biological signaling
      responses. In signaling from the T-cell receptor (TCR), the Gads C-terminal SH3
      domain binds a core RxxK sequence motif in the SLP-76 scaffold. We show that
      residues surrounding this motif are largely optimized for binding the Gads C-SH3
      domain resulting in a high-affinity interaction (K(D)=8-20 nM) that is essential
      for efficient TCR signaling in Jurkat T cells, since Gads-mediated signaling
      declines with decreasing affinity. Furthermore, the SLP-76 RxxK motif has evolved
      a very high specificity for the Gads C-SH3 domain. However, TCR signaling in
      Jurkat cells is tolerant of potential SLP-76 crossreactivity, provided that very
      high-affinity binding to the Gads C-SH3 domain is maintained. These data provide
      a quantitative argument that the affinity of the Gads C-SH3 domain for SLP-76 is
      physiologically important and suggest that the integrity of TCR signaling in vivo
      is sustained both by strong selection of SLP-76 for the Gads C-SH3 domain and by
      a capacity to buffer intrinsic crossreactivity.

PMID- 17235284
TI  - Bak and Bax are non-redundant during infection- and DNA damage-induced apoptosis.
AB  - Mitochondrial outer membrane permeabilization (MOMP) and release of mitochondrial
      intermembrane proteins like cytochrome c are critical steps in the control of
      apoptosis. Previous work has shown that MOMP depends on the functionally
      redundant multidomain proapoptotic proteins, Bak and Bax. Here we demonstrate
      that Bak and Bax are functionally non-redundant during Neisseria gonorrhoeae
      (Ngo)- and cisplatin-induced apoptosis. While the activation of Bak is caspase
      independent Bax activation needs Bak and active caspases. Silencing of either Bak
      or Bax resists both Ngo- and cisplatin- but not TNFalpha-induced apoptosis.
      Activation of Bak is required to release cytochrome c from the mitochondria;
      however, Bax is still required to activate effector caspases. Thus, both Bak and
      Bax are necessary to accomplish DNA damage and Ngo-induced apoptosis.

PMID- 17235285
TI  - Phosphorylation-independent interaction between 14-3-3 and exoenzyme S: from
      structure to pathogenesis.
AB  - 14-3-3 proteins are phosphoserine/phosphothreonine-recognizing adapter proteins
      that regulate the activity of a vast array of targets. There are also examples of
      14-3-3 proteins binding their targets via unphosphorylated motifs. Here we
      present a structural and biological investigation of the phosphorylation
      independent interaction between 14-3-3 and exoenzyme S (ExoS), an ADP
      ribosyltransferase toxin of Pseudomonas aeruginosa. ExoS binds to 14-3-3 in a
      novel binding mode mostly relying on hydrophobic contacts. The 1.5 A crystal
      structure is supported by cytotoxicity analysis, which reveals that substitution
      of the corresponding hydrophobic residues significantly weakens the ability of
      ExoS to modify the endogenous targets RAS/RAP1 and to induce cell death.
      Furthermore, mutation of key residues within the ExoS binding site for 14-3-3
      impairs virulence in a mouse pneumonia model. In conclusion, we show that ExoS
      binds 14-3-3 in a novel reversed orientation that is primarily dependent on
      hydrophobic residues. This interaction is phosphorylation independent and is
      required for the function of ExoS.

PMID- 17235286
TI  - Afferent neurotransmission mediated by hemichannels in mammalian taste cells.
AB  - In mammalian taste buds, ionotropic P2X receptors operate in gustatory nerve
      endings to mediate afferent inputs. Thus, ATP secretion represents a key aspect
      of taste transduction. Here, we characterized individual vallate taste cells
      electrophysiologically and assayed their secretion of ATP with a biosensor. Among
      electrophysiologically distinguishable taste cells, a population was found that
      released ATP in a manner that was Ca(2+) independent but voltage-dependent. Data
      from physiological and pharmacological experiments suggested that ATP was
      released from taste cells via specific channels, likely to be connexin or
      pannexin hemichannels. A small fraction of ATP-secreting taste cells responded to
      bitter compounds, indicating that they express taste receptors, their G-protein
      coupled and downstream transduction elements. Single cell RT-PCR revealed that
      ATP-secreting taste cells expressed gustducin, TRPM5, PLCbeta2, multiple
      connexins and pannexin 1. Altogether, our data indicate that tastant-responsive
      taste cells release the neurotransmitter ATP via a non-exocytotic mechanism
      dependent upon the generation of an action potential.

PMID- 17235287
TI  - Activation domains drive nucleosome eviction by SWI/SNF.
AB  - ATP-dependent chromatin remodeling complexes play a critical role in chromatin
      dynamics. A large number of in vitro studies have pointed towards nucleosome
      sliding as the principal remodeling outcome of SWI/SNF action, whereas few have
      described histone octamer transfer as the principal outcome. In contrast, recent
      in vivo studies have linked the activity of SWI/SNF to histone eviction in trans
      from gene promoters. In this study, we have found that the chimeric transcription
      factor Gal4-VP16 can enhance SWI/SNF histone octamer transfer activity, resulting
      in targeted histone eviction from a nucleosome probe. This effect is dependent on
      the presence of the activation domain. We observed that under conditions
      mimicking the in vivo relative abundance of SWI/SNF with respect to the total
      number of nucleosomes in a cell nucleus, the accessibility of the transcription
      factor binding site is the first determinant in the sequence of events leading to
      nucleosome remodeling. We propose a model mechanism for this transcription factor
      mediated enhancement of SWI/SNF octamer transfer activity.

PMID- 17235289
TI  - Suspension packaging cell lines for the simplified generation of T-cell receptor
      encoding retrovirus vector particles.
AB  - The transfer of T-cell receptor (TCR) genes into primary human T-cells to endow
      their specificity toward virus-infected and tumor cells is becoming an
      interesting tool for immunotherapy. TCR-modified T cells are mainly generated by
      retrovirus-mediated gene transfer. To produce TCR-retrovirus particles,
      fibroblast packaging cell lines are the most common tool. We constructed two
      packaging cell lines based on the human suspension T-cell lymphoma line Deltabeta
      Jurkat, which lacks endogenous TCRbeta-chains and is therefore unable to express
      CD3 complexes on the cell surface. After supply of gag-pol (murine leukemia virus
      (Mo-MLV)) and env (GALV or MLV-10A1) genes, a green fluorescent protein (GFP)
      encoding retrovirus vector was transduced into both packaging cell clones, which
      then stably produced GFP-retroviruses with titers of up to 4 x 10(5) infectious
      particles (IP)/ml. After transfer of a TCRalpha/beta-encoding retrovirus vector,
      Deltabeta-Jurkat/GALV and Deltabeta-Jurkat/10A1 cells expressed CD3 molecules on
      the cell surface. CD3-high expressing packaging cells were enriched by
      fluorescence-activated cell sorter sorting. In these cells, the CD3 expression
      level directly correlated with the titer of vector particles. TCR-retroviruses
      efficiently transduced human T-cell lines and primary T cells. In conclusion, the
      method allowed the fast and easy generation of high virus titer supernatants for
      TCR gene transfer.

PMID- 17235290
TI  - Species differences in transgene DNA uptake in hepatocytes after adenoviral
      transfer correlate with the size of endothelial fenestrae.
AB  - Sinusoidal fenestrae may restrict the transport of gene transfer vectors
      according to their size. Using Vitrobot technology and cryo-electron microscopy,
      we show that the diameter of human adenoviral serotype 5 vectors is 93 nm with
      protruding fibers of 30 nm. Thus, a diameter of fenestrae of 150 nm or more is
      likely to be sufficient for passage of vectors from the sinusoidal lumen to the
      space of Disse and subsequent uptake of vectors in hepatocytes. The average
      diameter of fenestrae in New Zealand White rabbits (103+/-1.3 nm) was 1.4-fold
      (P<0.0001) lower than in C57BL/6 mice (141+/-5.4 nm). The percentage of
      sinusoidal fenestrae with a diameter larger than 150 nm was 10-fold (P<0.01)
      lower in rabbits (3.2+/-0.24%) than in C57BL/6 mice (32+/-5%), and this resulted
      in 8.8-fold (P=0.01) lower transgene DNA levels in hepatocytes in rabbits after
      adenoviral transfer. Injection of N-acetylcysteine combined with transient liver
      ischemia preceding intraportal transfer in rabbits increased the percentage of
      sinusoidal fenestrae above 150 nm 2.0-fold (P<0.001) and increased transgene DNA
      levels in hepatocytes 6.6-fold (P<0.05). In conclusion, species differences in
      transgene DNA uptake in hepatocytes after adenoviral transfer correlate with the
      diameter of fenestrae.

PMID- 17235288
TI  - Murine bilateral retinoblastoma exhibiting rapid-onset, metastatic progression
      and N-myc gene amplification.
AB  - Human retinoblastoma is a pediatric cancer initiated by RB gene mutations in the
      developing retina. We have examined the origins and progression of retinoblastoma
      in mouse models of the disease. Retina-specific inactivation of Rb on a p130-/-
      genetic background led to bilateral retinoblastoma with rapid kinetics, whereas
      on a p107-/- background Rb mutation caused predominantly unilateral tumors that
      arose with delayed kinetics and incomplete penetrance. In both models,
      retinoblastomas arose from cells at the extreme periphery of the murine retina.
      Furthermore, late retinoblastomas progressed to invade the brain and metastasized
      to the cervical lymph nodes. Metastatic tumors lacking Rb and p130 exhibited
      chromosomal changes revealed by representational oligonucleotide microarray
      analysis including high-level amplification of the N-myc oncogene. N-myc was
      found amplified in three of 16 metastatic retinoblastomas lacking Rb and p130 as
      well as in retinoblastomas lacking Rb and p107. N-myc amplification ranged from 6
      to 400-fold and correlated with high N-myc-expression levels. These murine
      models closely resemble human retinoblastoma in their progression and secondary
      genetic changes, making them ideal tools for further dissection of steps to
      tumorigenesis and for testing novel therapies.

PMID- 17235292
TI  - Gene expression imaging by enzymatic catalysis of a fluorescent probe via
      membrane-anchored beta-glucuronidase.
AB  - Development of nonimmunogenic and specific reporter genes to monitor gene
      expression in vivo is important for the optimization of gene therapy protocols.
      We developed a membrane-anchored form of mouse beta-glucuronidase (mbetaG) as a
      reporter gene to hydrolyze a nonfluorescent glucuronide probe (fluorescein di
      beta-D-glucuronide, (FDGlcU) to a highly fluorescent reporter to assess the
      location and persistence of gene expression. A functional beta-glucuronidase
      (betaG) was stably expressed on the surface of murine CT26 colon adenocarcinoma
      cells where it selectively hydrolyzed the cell-impermeable FDGlcU probe. FDGlcU
      was also preferentially converted to fluorescent probe by (betaG) on CT26 tumors.
      The fluorescent intensity in betaG-expressing CT26 tumors was 240 times greater
      than the intensity in control tumors. Selective imaging of gene expression was
      also observed after intratumoral injection of adenoviral betaG vector into
      carcinoma xenografts. Importantly, mbetaG did not induce an antibody response
      after hydrodynamic plasmid immunization of Balb/c mice, indicating that the
      reporter gene product displayed low immunogenicity. A membrane-anchored form of
      human betaG also allowed in vivo imaging, demonstrating that human betaG can be
      employed for imaging. This imaging system therefore, displays good selectivity
      with low immunogenicity and may help assess the location, magnitude and duration
      of gene expression in living animals and humans.

PMID- 17235291
TI  - Identification of cell-type-specific promoters within the brain using lentiviral
      vectors.
AB  - The development of cell-type-specific mini-promoters for genetic studies is
      complicated by a number of issues. Here, we describe a general method for the
      relatively rapid screening of specific promoter activity in cell culture, in
      acute brain slice preparations and in vivo. Specifically, we examine the activity
      of an approximately 3 kb promoter region from the neuroactive peptide
      cholecystokinin (CCK) compared to the commonly used cytomegalovirus promoter. We
      find a high degree of cell-type selectivity in vivo using lentiviral approaches
      in rats and traditional transgenic approaches in mice. Appropriate colocalization
      of Cre-recombinase and CCK gene expression is found within the hippocampus, when
      the CCK promoter is driving either the expression of Cre-recombinase or green
      fluorescent protein. We also demonstrate fluorescent identification of CCK
      positive interneurons that allows for cell-type-specific electrophysiologic
      studies in rats and mice. In conclusion, these studies identify a functional mini
      promoter for the CCK gene and outline a novel and sensitive general method to
      test activity of selective promoters in vitro and in vivo. This approach may
      allow for the more rapid identification of specific promoters for use with
      transgenic animals, in genetically modified viruses, and in the design of
      targeted, therapeutic gene-delivery systems.

PMID- 17235294
TI  - RNAi gets vote of confidence from big pharma.

PMID- 17235293
TI  - Neuroprotective effect of adenoviral-mediated gene transfer of TIMP-1 and -2 in
      ischemic brain injury.
AB  - Gene therapy may be a promising approach for treatment of brain ischemia. We and
      others previously demonstrated that increased activity of matrix
      metalloproteinases (MMPs) contributes to the tissue damage that results from
      ischemic injury. The proteolysis of MMPs is tightly controlled by tissue
      inhibitors of MMPs (TIMPs). In this study, we examined whether adenoviral
      mediated gene transfer of TIMP-1 and TIMP-2 could protect against neuronal damage
      induced by global cerebral ischemia in mice. An adenovirus expressing TIMP-1 or
      TIMP-2 (AdTIMP-1 or AdTIMP-2) or a control adenovirus (RAd60) or vehicle was
      injected into the striatum 3 days before transient global cerebral ischemia. The
      extent of neuronal damage was quantified 3 days post-ischemia. There was no
      significant difference in the extent of neuronal damage in vehicle as compared to
      RAd60-treated mice. In contrast, neuronal damage was reduced, by approximately
      50%, after gene transfer of AdTIMP-1 (P<0.001) and AdTIMP-2 (P< 0.01) as compared
      to controls. This study provides the first in vivo evidence of the protective
      effects of TIMP-1 and TIMP-2 via gene transfer in global ischemia.

PMID- 17235297
TI  - A peptide fusion a day keeps the aggregates away.

PMID- 17235298
TI  - Armed interference: oncolytic viruses engineered to carry antitumor shRNAs.

PMID- 17235299
TI  - Viral vector-mediated and cell-based therapies for treatment of cystic fibrosis.
AB  - Gene and cell-based therapies are considered to be potentially powerful new
      approaches for the management of cystic fibrosis (CF) lung disease. Despite
      tremendous efforts that have been made, especially in studies to understand the
      obstacles to gene delivery, major challenges to the application of these
      approaches remain to be solved. This article will review the advancements made
      and challenges remaining in the development of viral vector-mediated and cell
      based approaches to treat patients with CF.

PMID- 17235300
TI  - Adeno-associated virus type 5 reduces learning deficits and restores glutamate
      receptor subunit levels in MPS VII mice CNS.
AB  - A major challenge in treating lysosomal storage diseases with enzyme therapy is
      correcting symptoms in the central nervous system (CNS). This study used a murine
      model of mucopolysaccharidosis type VII (MPS VII) to test whether pathological
      and functional CNS defects could be corrected by expressing beta-glucuronidase
      via bilateral intrastriatal injection of adeno-associated virus type 5
      (AAV5betagluc) vectors. After injecting AAV5betagluc, different brain regions
      expressed active beta-glucuronidase, which corrected lysosomal storage defects.
      Compared to age-matched littermates, adult MPS VII mice were impaired in spatial
      learning and memory, as measured by the repeated acquisition and performance
      chamber (RAPC) assay. AAV5betagluc-treated MPS VII mice improved significantly in
      the RAPC assay, relative to saline-injected littermates. Moreover, our studies
      reveal that cognitive changes in MPS VII mice correlate with decreased N-methyl-d
      aspartate and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor
      expression. Importantly, AAV5betagluc delivery restored glutamate receptor
      levels. Together, these data demonstrate that AAV5 vectors deliver a
      therapeutically effective beta-glucuronidase gene to the CNS and further suggest
      a possible mechanism underlying spatial learning defects in MPS VII mice.

PMID- 17235301
TI  - Infectious delivery and expression of a 135 kb human FRDA genomic DNA locus
      complements Friedreich's ataxia deficiency in human cells.
AB  - Friedreich's ataxia (FA) is the most common recessive ataxia, affecting 1-2 in
      50,000 Caucasians, and there is currently no effective cure or treatment. FA
      results from a deficiency of the mitochondrial protein frataxin brought about by
      a repeat expansion in intron 1 of the FRDA gene. The main areas affected are the
      central nervous system (particularly the spinocerebellar system) and cardiac
      tissue. Therapies aimed at alleviating the neurological degeneration have proved
      unsuccessful to date. Here, we describe the construction and delivery of high
      capacity herpes simplex virus type 1 (HSV-1) amplicon vectors expressing the
      entire 80 kb FRDA genomic locus, driven by the endogenous FRDA promoter and
      including all introns and flanking regulatory sequences within a 135 kb genomic
      DNA insert. FA patient primary fibroblasts deficient in frataxin protein and
      exhibiting sensitivity to oxidative stress were transduced at high efficiency by
      FRDA genomic locus vectors. Following vector transduction, expression of FRDA
      protein by immunofluorescence was shown. Finally, functional complementation
      studies demonstrated restoration of the wild-type cellular phenotype in response
      to oxidative stress in transduced FA patient cells. These results suggest the
      potential of the infectious bacterial artificial chromosome-FRDA vectors for gene
      therapy of FA.

PMID- 17235302
TI  - Adenovirus transduction is required for the correction of diabetes using Pdx-1 or
      Neurogenin-3 in the liver.
AB  - The regeneration of insulin-producing cells in vivo has emerged as a promising
      method for treating type I diabetes. Pancreatic duodenal homeobox-1 (Pdx-1),
      NeuroD, and Neurogenin-3 (Ngn3) are pancreatic transcription factors important
      for the development of insulin-producing cells in the liver. Other groups have
      demonstrated that adenoviral-mediated transgene expression of these transcription
      factors in the liver can reverse hyperglycemia in diabetic mice. We delivered Pdx
      1 and Ngn3 to the livers of diabetic mice using adeno-associated virus (AAV)
      serotype 8, a vector that has been shown to result in non-toxic, persistent, high
      level expression of the transgene. We were unable to correct hyperglycemia in
      mice with streptozotocin-induced diabetes using AAV vectors expressing Pdx-1 and
      Ngn3. However, when we co-delivered these transcription factor expression
      cassettes in non-viral vectors with an irrelevant adenoviral vector, we were able
      to correct hyperglycemia in diabetic animals. Further studies demonstrated that
      an antigen-dependent immune response elicited by the adenoviral capsid together
      with the expression of a pancreatic transcription factor was required for
      restoration of serum insulin levels by the liver. Our results suggest that a host
      response to adenovirus in combination with expression of a pro-endocrine pancreas
      transcription factor is sufficient to induce insulin production in the livers of
      diabetic mice.

PMID- 17235303
TI  - Long-term suppression of experimental arthritis following intramuscular
      administration of a pseudotyped AAV2/1-TNFR:Fc Vector.
AB  - We previously reported that administration of an adeno-associated virus 2 (AAV2)
      vector encoding a rat tumor necrosis factor (TNF) receptor-immunoglobulin Fc
      (TNFR:Fc) fusion gene to rats with streptococcal cell wall-induced arthritis
      resulted in suppression of joint inflammation and cartilage and bone destruction,
      as well as expression of joint proinflammatory cytokines. In this study, we used
      an alternate rat model of arthritis to compare the serum levels and duration of
      TNFR:Fc protein expression following intramuscular administration of pseudotyped
      AAV-TNFR:Fc vectors based on serotypes 1, 2, and 5. All three pseudotyped AAV
      TNFR:Fc vectors led to sustained expression of serum TNFR:Fc protein for at least
      one year. Serum TNFR:Fc protein levels in rats administered intramuscularly with
      AAV2/1-TNFR:Fc vector were up to 100- and 10-fold higher than in rats
      administered the AAV2-TNFR:Fc or AAV2/5-TNFR:Fc vectors, respectively. A single
      intramuscular administration of AAV2/1-TNFR:Fc vector at vector doses ranging
      from 10(10) to 10(12) DNase-resistant particles (DRP) per animal, resulted in
      complete and long-term suppression of recurrent joint inflammation for at least
      150 days. Our results establish a proof of concept for administration of an
      AAV2/1-TNFR:Fc vector to the muscle to achieve long-term, sustained and
      therapeutically relevant levels of TNFR:Fc protein to treat chronic systemic
      inflammatory joint diseases.

PMID- 17235304
TI  - Comparison of d-g3139 and its enantiomer L-g3139 in melanoma cells demonstrates
      minimal in vitro but dramatic in vivo chiral dependency.
AB  - G3139 (Genasense), an 18mer phosphorothioate antisense oligonucleotide targeted
      to the initiation codon region of the Bcl-2 messenger RNA (mRNA), downregulates
      Bcl-2 protein and mRNA expression in many cell lines. However, both the in vitro
      and in vivo mechanisms of action of G3139 are still uncertain. The isosequential
      L-deoxyribose enantiomer L-G3139, which does not downregulate Bcl-2 expression,
      was synthesized to study the role of the Bcl-2 protein in melanoma cells. Both D
      G3139 and L-G3139 bind nonspecifically to basic fibroblast growth factor with
      approximately the same K(c), and cause highly effective inhibition of net
      formation in 518A2 melanoma cells on Matrigel. The uptakes of D-G3139 and L-G3139
      in melanoma cells were also similar. However, unlike D-G3139, L-G3139 does not
      produce poly ADP-ribose polymerase-1 and procaspase-3 cleavage at 9.5 h after the
      initiation of the transfection, but can activate the intrinsic pathway of
      apoptosis at approximately 48 h. Furthermore, treatment of A375 melanoma human
      xenografts in severe combined immunodeficiency (SCID) mice demonstrates that
      tumor growth is not inhibited by L-G3139, whereas D-G3139 significantly inhibits
      the rate of tumor growth. Furthermore, the immunostimulatory properties of L
      G3139 appear to be nil, which differs dramatically from those of D-G3139. In
      conclusion, profound differences exist between D-G3139 and L-G3139 in vivo
      despite their similarities in vitro.

PMID- 17235305
TI  - Oncolytic HSV and erlotinib inhibit tumor growth and angiogenesis in a novel
      malignant peripheral nerve sheath tumor xenograft model.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs), driven in part by hyperactive
      Ras and epidermal growth factor receptor (EGFR) signaling, are often incurable.
      Testing of therapeutics for MPNST has been hampered by lack of adequate xenograft
      models. We previously documented that human MPNST cells are permissive for lytic
      infection by oncolytic herpes simplex viruses (oHSV). Herein we developed and
      characterized a xenograft model of human MPNST and evaluated the antitumor
      effects of oHSV mutants (G207 and hrR3) and the EGFR inhibitor, erlotinib.
      Additive cytotoxicity of these agents was found in human MPNST cell lines,
      suggesting that EGFR signaling is not critical for virus replication. Mice
      bearing human MPNST tumors treated with G207 or hrR3 by intraperitoneal or
      intratumoral injection showed tumor-selective virus biodistribution, virus
      replication, and reduced tumor burden. oHSV injection demonstrated more dramatic
      antitumor activity than erlotinib. Combination therapies showed a trend toward an
      increased antiproliferative effect. Both oHSV and erlotinib were antiangiogenic
      as measured by proangiogenic gene expression, effect on endothelial cells and
      xenograft vessel density. Overall, oHSVs showed highly potent antitumor effects
      against MPNST xenografts, an effect not diminished by EGFR inhibition. Our data
      suggest that inclusion of MPNSTs in clinical trials of oHSV is warranted.

PMID- 17235306
TI  - mda-7 In combination with bevacizumab treatment produces a synergistic and
      complete inhibitory effect on lung tumor xenograft.
AB  - Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth
      factor (VEGF), has shown antitumor activity by inhibiting tumor angiogenesis in
      preclinical and clinical studies. However, bevacizumab monotherapy does not
      induce complete tumor regression. Therefore, additional treatments must be
      combined with bevacizumab to promote tumor regression. We previously showed that
      melanoma differentiation associated gene-7 (mda-7) protein exerts potent
      antitumor and antiangiogenic activity. Thus, in this study, we investigated the
      therapeutic effects of mda-7 in combination with bevacizumab using lung cancer as
      a model. In vitro, treatment of human umbilical vein endothelial cells with
      conditioned medium from Ad-mda7 plus bevacizumab-treated lung tumor cells showed
      reduced VEGF ligand-receptor binding, and decreased cell survival, resulting in
      growth arrest and apoptosis. In vivo, treatment of subcutaneous lung tumor
      xenografts with bevacizumab plus Ad-mda7 resulted in significant tumor growth
      inhibition and improved survival compared to tumor growth in control mice.
      Furthermore, tumors in all the Ad-mda7 plus bevacizumab-treated mice completely
      regressed, and these were tumor free through the study's end. Molecular analysis
      showed enhanced tumor cell apoptosis and reduced VEGF and CD31 expression in Ad
      mda7 plus bevacizumab-treated tumors. Thus, Ad-mda7 and bevacizumab treatment
      produces a synergistic and complete therapeutic effect against human lung cancer.

PMID- 17235307
TI  - VEGF-specific short hairpin RNA-expressing oncolytic adenovirus elicits potent
      inhibition of angiogenesis and tumor growth.
AB  - RNA interference is being developed to treat cancer. Although highly target
      specific, its use has been limited by its short duration of expression. To
      overcome this shortcoming, we constructed an oncolytic adenovirus (Ad)-based
      short hairpin RNA (shRNA) expression system (Ad-DeltaB7-shVEGF) against vascular
      endothelial growth factor (VEGF), a key mediator in angiogenesis. To demonstrate
      the VEGF-specific nature of this Ad-based shRNA, replication-incompetent Ad
      expressing VEGF-specific shRNA (Ad-DeltaE1-shVEGF) was also generated. Ad-DeltaE1
      shVEGF was highly effective in reducing VEGF expression, and elicited an
      antiangiogenic effect in vitro and in vivo. Similarly, Ad-DeltaB7-shVEGF
      exhibited potent antiangiogenic effects in the matrigel plug assay. Moreover, Ad
      DeltaB7-shVEGF demonstrated a greater antitumor effect and enhanced survival
      compared to the cognate control oncolytic Ad, Ad-DeltaB7. Ad-DeltaB7-shVEGF
      induced significant reduction in tumor vasculature, verifying the antiangiogenic
      mechanism. Furthermore, both the duration and magnitude of gene silencing by Ad
      DeltaB7-shVEGF was greater than Ad-DeltaE1-shVEGF. These results suggest that the
      combined effects of oncolytic viral therapy and cancer cell-specific expression
      of VEGF-targeted shRNA elicits greater antitumor effect than an oncolytic Ad
      alone.

PMID- 17235308
TI  - Protein transduction domain-mediated delivery of QBP1 suppresses polyglutamine
      induced neurodegeneration in vivo.
AB  - Many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease,
      and the polyglutamine (polyQ) diseases share common features including abnormal
      aggregation of misfolded proteins and their deposition as inclusion bodies in the
      brain. The polyQ diseases are caused by abnormal expansion of a polyQ stretch in
      each disease-causing protein, which triggers these proteins to form aggregates.
      We previously showed that genetic expression of the aggregate inhibitor peptide
      polyQ binding peptide 1 (QBP1) suppresses polyQ-induced neurodegeneration in
      Drosophila. However, to establish a molecular therapy using QBP1, QBP1 needs to
      be delivered into cells by its administration. In this study, we employed protein
      transduction domains (PTDs) to enable the efficient intracellular delivery of
      QBP1. We show here that fusion with a PTD enables the efficient intracellular
      delivery of QBP1, and that PTD-QBP1 treatment suppressed polyQ-induced
      cytotoxicity in cultured cells. Most importantly, oral administration of PTD-QBP1
      successfully suppressed polyQ-induced premature death as well as polyQ inclusion
      body formation in a Drosophila model of the polyQ diseases, demonstrating its
      therapeutic effect against polyQ-induced neurodegeneration in vivo. Our study
      indicates that PTD-mediated delivery of aggregate inhibitor peptides is a
      promising therapeutic strategy for neurodegenerative diseases with abnormal
      aggregation of misfolded proteins.

PMID- 17235309
TI  - Evidence for intercellular trafficking of VP22 in living cells.
AB  - The intercellular trafficking property of the herpes simplex virus type 1
      tegument protein VP22 makes it a promising tool for overcoming low transduction
      efficiencies in gene therapy. However, recent reports suggest not only that VP22
      cannot facilitate intercellular spreading and that trafficking of VP22 fusion
      proteins results from artifacts of cell fixation only. To provide direct evidence
      for the presence or absence of VP22-mediated intercellular trafficking, we
      generated an adenoviral vector with a dual expression cassette for VP22 fused to
      green fluorescent protein (VP22 GFP) and DsRed under the control of distinct
      human cytomegalovirus immediate-early enhancer/promoter regions. Using this
      vector, we were able to distinguish clearly between primary transduced cells and
      cells taking up VP22GFP by intercellular trafficking. To our knowledge, for the
      first time, we could demonstrate by live-cell confocal fluorescence microscopy
      that VP22GFP can be found intracellularly in unfixed recipient cells. The extent
      of VP22 spread was similar in paraformaldehyde-fixed cells and unfixed cells as
      demonstrated by fluorescence-activated cell sorting analysis. We thus confirmed
      the ability of VP22-mediated intercellular trafficking in live unfixed cells.

PMID- 17235311
TI  - A two-hybrid screen identifies cathepsins B and L as uncoating factors for adeno
      associated virus 2 and 8.
AB  - Vectors based on different serotypes of adeno-associated virus hold great promise
      for human gene therapy, based on their unique tissue tropisms and distinct
      immunological profiles. A particularly interesting candidate is AAV8, which can
      efficiently and rapidly transduce a wide range of tissues in vivo. To further
      unravel the mechanisms behind AAV8 transduction, we used yeast two-hybrid
      analyses to screen a mouse liver complementary DNA library for cellular proteins
      capable of interacting with the viral capsid proteins. In total, we recovered
      approximately 700 clones, comprising over 300 independent genes. Sequence
      analyses revealed multiple hits for over 100 genes, including two encoding the
      endosomal cysteine proteases cathepsins B and L. Notably, these two proteases
      also physically interacted with the corresponding portion of the AAV2 capsid in
      yeast, but not with AAV5. We demonstrate that cathepsins B and L are essential
      for efficient AAV2- and AAV8-mediated transduction of mammalian cells, and
      document the ability of purified cathepsin B and L proteins to bind and cleave
      intact AAV2 and AAV8 particles in vitro. These data suggest that cathepsin
      mediated cleavage could prime AAV capsids for subsequent nuclear uncoating, and
      indicate that analysis of additional genes recovered in our screen may help to
      further elucidate the mechanisms behind transduction by AAV8 and related
      serotypes.

PMID- 17235310
TI  - Design of tissue-specific regulatory cassettes for high-level rAAV-mediated
      expression in skeletal and cardiac muscle.
AB  - Systemic delivery of recombinant adeno-associated virus (rAAV) 6 vectors mediates
      efficient transduction of the entire striated musculature, making this an
      attractive strategy for muscle gene therapy. However, owing to widespread
      transduction of non-muscle tissues, optimization of this method would benefit
      from the use of muscle-specific promoters. Most such promoters either lack high
      level expression in certain muscle types or are too large for inclusion in rAAV
      vectors encoding microdystrophin. Here, we describe novel regulatory cassettes
      based on enhancer/promoter regions of murine muscle creatine kinase (CK) and
      alpha-myosin heavy-chain genes. The strongest cassette, MHCK7 (770 bp), directs
      high-level expression comparable to cytomegalovirus and Rous sarcoma virus
      promoters in fast and slow skeletal and cardiac muscle, and low expression in the
      liver, lung, and spleen following systemic rAAV6 delivery in mice. Compared with
      CK6, our previous best cassette, MHCK7 activity is approximately 400-,
      approximately 50-, and approximately 10-fold higher in cardiac, diaphragm, and
      soleus muscles, respectively. MHCK7 also directs strong microdystrophin
      expression in mdx muscles. While further study of immune responses to MHCK7
      regulated microdystrophin expression is needed, this cassette is not active in
      dendritic cell lines. MHCK7 is thus a highly improved regulatory cassette for
      experimental studies of rAAV-mediated transduction of striated muscle.

PMID- 17235312
TI  - Targeted gene transfer to fetal rat lung interstitium by ultrasound-guided
      intrapulmonary injection.
AB  - In utero gene transfer to the developing lung may have clinical or research
      applications. In this study, we developed a new method for specifically targeting
      the fetal rat lung with adeno and lentiviral vectors encoding the enhanced green
      fluorescence protein (EGFP) marker gene at E15.5 using ultrasound biomicroscopy
      (UBM). Survival rate, morphometric parameters, viral biodistribution, and lung
      transduction efficiency were analyzed and compared to the intra-amniotic route of
      administration. Expression of EGFP started as early as 24 and 72 h after the
      injection of adenoviral and lentiviral vectors, respectively. Both vectors
      transduced lung parenchyma with gene expression limited to interstitial cells of
      the injected region, in contrast to intra-amniotic injection, which targeted the
      pulmonary epithelium. Expression of EGFP was most intense at E18.5 and E21.5 for
      adenoviral and lentiviral vectors, respectively. In contrast to lentivirus,
      adenoviral expression significantly declined until final analysis at 1 week of
      age. This study demonstrates the feasibility of targeting the fetal rat lung
      interstitium with viral vectors under UBM guidance during the pseudoglandular
      stage. This model system may facilitate in vivo studies of dynamic lung
      morphogenesis and could provide insight into the efficacy of prenatal gene
      transfer strategies for treatment of specific lung disorders.

PMID- 17235313
TI  - Optimizing aerosol gene delivery and expression in the ovine lung.
AB  - We have developed the sheep as a large animal model for optimizing cystic
      fibrosis gene therapy protocols. We administered aerosolized gene transfer agents
      (GTAs) to the ovine lung in order to test the delivery, efficacy, and safety of
      GTAs using a clinically relevant nebulizer. A preliminary study demonstrated GTA
      distribution and reporter gene expression throughout the lung after aerosol
      administration of plasmid DNA (pDNA):GL67 and pDNA:PEI complexes. A more
      comprehensive study examined the dose-response relationship for pDNA:PEI and
      assessed the influence of adjunct therapeutic agents. We found that the sheep
      model can differentiate between doses of GTA and that the anticholinergic,
      glycopyrrolate, enhanced transgene expression. Dose-related toxicity of GTA was
      reduced by aerosol administration compared to direct instillation. This large
      animal model will allow us to move toward clinical studies with greater
      confidence.

PMID- 17235314
TI  - Lentiviral vectors for T-cell suicide gene therapy: preservation of T-cell
      effector function after cytokine-mediated transduction.
AB  - Retroviral transfer of the Herpes Simplex thymidine kinase (HSVTK) suicide gene
      to donor T cells has been used as a safety strategy against graft-versus-host
      disease following allogeneic stem cell transplantation. The feasibility of this
      strategy in human studies has been demonstrated, but a number of limitations have
      become apparent. Preactivation of donor lymphocytes using mitogens or monoclonal
      antibodies is essential for retroviral transduction, but can compromise
      subsequent T-cell function in vivo. We report the application of lentiviral
      vectors for transduction of T cells in cytokine culture, without activation
      through the T-cell receptor. Using vectors encoding either enhanced green
      fluorescent protein or a truncated CD34/mutant HSVTK fusion selection/suicide
      construct, we investigated the properties of T cells after gene modification. We
      found that following cytokine stimulation, a fraction of T cells undergoes
      division, and transgene expression occurred predominantly in these cells.
      Antiviral and alloreactive responses were preserved in these populations, and in
      contrast to fully activated T cells, there was minimal perturbation of regulatory
      T-cell numbers. We conclude that the use of interleukin-7 for lentiviral
      transduction offers the greatest potential for gene transfer to T cells without
      loss of function, and is favored for the clinical production of suicide gene
      modified T cells.

PMID- 17235315
TI  - Modifying the proliferative state of target cells to control DNA expression and
      identifying cell types transfected in vivo.
AB  - Although the majority of current gene transfer techniques have focused on
      increasing the ability of the DNA to enter the cell, it is possible that changing
      the proliferative and migratory state of cells will influence the cells ability
      to take up and express plasmid DNA. This study was designed to test the
      hypothesis that growth factors (basic fibroblast growth factor (bFGF) and
      hepatocyte growth factor/scatter factor (HGF/SF)) used to alter the proliferative
      and migratory state of cells can alter plasmid DNA uptake and expression. In
      vitro studies indicate that enhancing cell proliferation with growth factor
      exposure enhances plasmid DNA uptake and expression. Furthermore, dual localized
      delivery of bFGF and plasmid DNA in vivo increases the expression, 3-6 times over
      control, as compared to plasmid delivery alone. Dual delivery of a factor
      promoting cell proliferation and a plasmid led to a further increase in the
      expression of the plasmid encoding bone morphogenetic protein-2 in a rat cranial
      defect by specific cell populations. The results of these studies suggest that
      increasing the proliferative state of target cell populations can enhance non
      viral gene transfer.

PMID- 17235316
TI  - EGF receptor activation decreases retroviral gene transfer through protein kinase
      C-delta.
AB  - Although much progress has been made in the design of retrovirus vectors, the
      interactions of recombinant retrovirus with host cells remain largely elusive.
      The inability of recombinant retrovirus to transduce non-dividing cells prompted
      several studies to determine optimal cocktails of growth factors and/or
      extracellular matrix molecules to promote gene transfer to slowly diving cells
      and stem cells. In contrast to previous reports that growth factors increased
      gene transfer, we found that treatment of human epidermal keratinocytes and
      several cell lines with epidermal growth factor receptor (EGFR) ligands EGF,
      transforming growth factor-alpha, or heparin-binding-EGF decreased gene transfer.
      Conversely, treatment with an EGFR function-blocking antibody or inhibition of
      EGFR tyrosine phosphorylation enhanced gene transfer in a dose-dependent manner.
      In addition, blocking protein kinase C (PKC)-delta but not PKC-zeta, with
      chemical inhibitors or small interfering RNA reversed the effects of EGF and
      restored gene transfer, indicating that the effect of EGFR activation is mediated
      through PKC-delta. Lastly, cell cycle analysis showed that the effect of EGFR
      activation on retroviral gene transfer was independent of the cell cycle status
      of target cells. Our results implicate EGFR and PKC-delta in retroviral infection
      and may have implications for retrovirus gene transfer or design of
      antiretroviral therapies.

PMID- 17235317
TI  - Toll-like receptor 9 triggers an innate immune response to helper-dependent
      adenoviral vectors.
AB  - A major obstacle to the clinical application of systemic adenoviral gene
      replacement therapy is the host innate immune response. Although recent studies
      have attempted to characterize the cellular basis for this response to
      systemically administered helper-dependent adenoviral vector (HD-Ad), the
      underlying molecular components of the innate immune repertoire required to
      recognize the viral vector have yet to be identified. Here, we show that primary
      macrophages can sense HD-Ad vectors via the Toll-like Receptor 9 (TLR9) and
      respond by increasing pro-inflammatory cytokine secretion. Moreover, TLR9 sensing
      is involved in the rapid innate immune response to HD-Ad in vivo. TLR9 deficiency
      attenuates the innate immune response to HD-Ad, whereas TLR9 blockade reduces the
      acute inflammatory response after intravenous injection of the vector. Moreover,
      HD-Ad upregulates TLR9 gene expression independent of TLR9 function, suggesting
      that additional innate signaling pathways work cooperatively with TLR9. The
      identification of the components of the innate immune response to adenovirus will
      facilitate the development of combinatorial therapy directed at increasing the
      maximal tolerated dose of systemically delivered adenoviral vectors.

PMID- 17235319
TI  - Type I interferon inhibits antibody responses induced by a chimpanzee adenovirus
      vector.
AB  - Recent studies have indicated that type I interferon (IFN) enhances antibody
      responses and promotes isotype switching. In this study, we analyzed the role of
      type I IFN signaling during the generation of transgene product-specific antibody
      responses elicited by recombinant adenovirus (Ad) vectors. A vector derived from
      a human Ad serotype (AdHu5) induced low levels of type I IFN following infection
      of dendritic cells (DCs) and stimulated normal transgene product-specific
      antibody responses in mice that have a defective type I IFN receptor (IFNAR(-/
      )). A vector derived from a chimpanzee Ad serotype (AdC68) induced very high
      levels of type I IFN following infection of DCs, and surprisingly, primed
      stronger transgene product-specific antibody responses in IFNAR(-/-) mice
      compared to wild-type mice. The increased antibody response in IFNAR(-/-) mice
      vaccinated with the AdC68 vector was mainly due to the generation of IgG1
      antibodies that were not elicited in wild-type mice. The induction of IgG1
      antibodies correlated with an increase in transgene product expression in IFNAR(
      /-) mice and was not associated with an increase in T helper 2 responses. We
      conclude that type I IFN, when induced at high levels, can downregulate transgene
      product expression of Ad vectors and inhibit the formation of optimal antibody
      responses.

PMID- 17235318
TI  - Dendritic cell function after gene transfer with adenovirus-calcium phosphate co
      precipitates.
AB  - Dendritic cells (DCs) are essential for initiating and directing antigen-specific
      T-cell responses. Genetic modification of DC is under study for cancer
      immunotherapy, vaccine development, and antigen-targeted immunosuppression.
      Adenovirus (Ad) type 5 (Ad5)-mediated gene transfer to mouse bone marrow DCs and
      human monocyte-derived DCs is inefficient because neither express the cognate
      high-affinity Ads receptor. We show that co-precipitating adenoviral vectors with
      calcium phosphate (CaPi) increased gene expression (2000-fold) and transduction
      efficiency (50-fold) in mouse DC, primarily owing to receptor-independent viral
      uptake. Moreover, Ad5:CaPi-treated DCs were activated to express the maturation
      surface molecules CD40 and CD86, and to secrete proinflammatory cytokines tumor
      necrosis factor-alpha and interleukin 6. However, neither DC transduction nor
      maturation was dependent on viral protein interactions with cell surface
      integrin. Ad5:CaPi also transduced human DC more efficiently than Ad5 alone,
      similar to a genetically modified vector (Ad5f35) targeted to the CD46 receptor.
      As such, this approach combines the efficiency of adenoviral-mediated endosomal
      escape and nuclear trafficking with the receptor independence of nonviral gene
      delivery. Importantly, CaPi co-precipitation could be used to functionally modify
      DC to activate and expand cytomegalovirus-specific memory cytotoxic T
      lymphocytes. This study identifies a simple technique to improve the efficacy of
      current Ad5 gene transfer, in support of clinical adoptive immunotherapy.

PMID- 17235320
TI  - Inhibitor of heat-shock protein 90 enhances the antitumor effect of DNA vaccine
      targeting clients of heat-shock protein.
AB  - Geldanamycin (GA), a heat-shock protein (HSP) 90 inhibitor, induces degradation
      of HSP90 client proteins, which may promote the presentation of degradation
      peptides with major histocompatibility complex class I on cancer cells. We
      hypothesized that GA may enhance the efficacy of DNA vaccination, and
      investigated the therapeutic effect of the combination of GA and a DNA vaccine
      against HSP90 clients p185(neu) and Met. The efficacy of various doses of GA
      combined with an N-terminal neu (N'-neu) DNA vaccine was investigated in a
      transplanted tumor constitutively overexpressing endogenous p185(neu). Low-dose
      (2.5 mug) but not high-dose (10 microg) GA enhanced the effect of N'-neu DNA
      vaccination on the inhibition of murine bladder tumor-2 tumors in syngeneic C3H
      mice. Anti-p185(neu) antibody titers were similar among all treated groups.
      Significantly increased infiltrations of CD8(+) T cells and NK cells were
      observed at tumor sites. GA sensitized tumor cells to the cytotoxic effects of
      lymphocytes. Depletion of CD8(+) T cells eliminated most of the therapeutic
      efficacy; in contrast, depletion of CD4(+) T cells enhanced the therapeutic
      efficacy. A similar enhancing effect was observed for the combination of GA and a
      DNA vaccine targeting the Met oncogene. Our results support the use of
      combination of GA and DNA vaccination against GA-targeted proteins.

PMID- 17235321
TI  - Enhanced cellular immune responses elicited by an engineered HIV-1 subtype B
      consensus-based envelope DNA vaccine.
AB  - An important goal for human immunodeficiency virus (HIV) vaccines is to develop
      immunogens that induce broader and more potent cellular immune responses. In this
      study of DNA vaccine potency, we constructed a novel subtype B env gene (EY2E1-B)
      with the goal of increasing vaccine antigen immune potency. The vaccine cassette
      was designed based on subtype B-specific consensus sequence with several
      modifications, including codon optimization, RNA optimization, the addition of a
      Kozak sequence, and a substituted immunoglobulin E leader sequence. The V1 and V2
      loops were shortened and the cytoplasmic tail was truncated to prevent envelope
      recycling. Three different strains of mice (BALB/c, C57BL/6, and HLA-A2
      transgenic mice) were immunized three times with pEY2E1-B or the primary DNA
      immunogen pEK2P-B alone. The analysis of specific antibody responses suggested
      that EY2E1-B could induce a moderate subtype B-specific antibody response.
      Moreover, this construct was up to four times more potent at driving cellular
      immune responses. Epitope mapping results indicated that there is an increase in
      the breadth and magnitude of cross-reactive cellular responses induced by the
      EY2E1-B immunogen. These properties suggest that such a synthetic immunogen
      deserves further examination for its potential to serve as a component antigen in
      an HIV vaccine cocktail.

PMID- 17235322
TI  - Hydrodynamic limb vein delivery of a xenogeneic DNA cancer vaccine effectively
      induces antitumor immunity.
AB  - Tumor-associated antigens (TAA) are typically poorly immunogenic "self" antigens.
      An effective strategy to break tolerance and induce antitumor immunity is by
      genetic vaccination, employing the orthologous TAA-sequence from a different
      species. We recently developed a clinically relevant approach for intravascular
      hydrodynamic limb vein (HLV) delivery of nucleic acids to skeletal muscle. Using
      the human gp100 xenogeneic TAA in the murine B16 melanoma model, we show that
      genetic vaccination of mice by HLV plasmid DNA delivery was highly effective at
      breaking tolerance against the homologous murine gp100 (mgp100) TAA and induced
      prophylactic antitumor protection. HLV vaccination resulted in an anti-hgp100
      humoral and cellular response, with 4-5% of CD8(+) T cells being gp100(25-33)
      epitope-specific. Vaccinated animals demonstrated in vivo cytolytic activity
      against human and mgp100(25-33) peptide-pulsed targets. Antitumor immunity could
      be adoptively transferred by splenocytes from human gp100-vaccinated animals.
      Furthermore, a durable antitumor memory response was established as approximately
      3% of CD8(+) T cells were gp100(25-33) antigen-specific in mice 6 months after
      vaccination. Following a single HLV human gp100 DNA boost, this level increased
      to approximately 17% and protected animals from subsequent B16 tumor rechallenge.
      Our results warrant further consideration of HLV as a clinically relevant method
      for cancer gene therapy.

PMID- 17235323
TI  - Autologous transplantation of muscle precursor cells modified with a lentivirus
      for muscular dystrophy: human cells and primate models.
AB  - Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin.
      We tested the ability of lentiviral vectors to deliver a transgene into myogenic
      cells before their transplantation. Enhanced green fluorescent protein (eGFP)
      transgene was efficiently transferred into cells and eGFP-positive fibers were
      generated following transplantation. An eGFP-micro-dystrophin transgene under the
      control of a cytomegalovirus promoter was then transferred with the same viral
      vector but caused some toxicity to the mono-nucleated cells. We then used instead
      a muscle creatine kinase promoter. Dystrophin expression was observed in the
      muscle fibers after the transplantation of such genetically modified cells into
      mdx and severe combined immunodeficient mice. Micro-dystrophin expression was
      also observed in monkey muscles a month after allogenic or autologous
      transplantation of genetically modified myoblasts. Therapeutic exon skipping was
      induced by infecting myoblasts of a DMD patient, deleted for dystrophin exons 49
      and 50, with a lentivirus expressing a U7 small nuclear RNA containing antisense
      sequences against exon 51. The modification led to correct exon skipping and to
      the expression of a quasi-dystrophin in vitro and in vivo. These results
      demonstrate the feasibility of lentiviral-based ex vivo gene therapy for DMD.

PMID- 17235324
TI  - Adrenocorticotropin hormone stimulates interleukin-18 expression in human HaCaT
      keratinocytes.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis is activated by stress. This
      involves the production of corticotropin releasing hormone (CRH) with the
      subsequent release of proopiomelanocortin (POMC) peptides, of which
      adrenocorticotropin hormone (ACTH) is most important. Although the skin has the
      capacity to produce CRH and POMC peptides, the immunomodulatory roles of ACTH in
      skin are yet unknown. IL-18 has been known to affect cells involved in the
      inflammatory response. In this study, we aimed to identify the regulatory effect
      of ACTH on IL-18 expression of skin keratinocytes. Exposure of HaCaT cells to
      ACTH stimulated formation of IL-18 mRNA transcript and its protein products in a
      dose-dependent manner. Furthermore, we suggest that ACTH-induced IL-18 production
      is via the caspase-1 activation pathway, as IL-18 production induced by ACTH
      could be suppressed by caspase-1 inhibitor, and ACTH could increase caspase-1
      activity. The effect of ACTH on IL-18 production was blocked by specific
      inhibitors of p38 kinase (SB203580) or extracellular signal-regulated kinase
      (ERK) (PD98059). In addition, ACTH-induced rapid phosphorylation of p38 kinase
      and ERK, and ACTH signaling occurred via melanocortin receptor 1 (MC1R) and
      receptor 2 (MC2R). These results suggest that ACTH stimulates IL-18 expression in
      human keratinocytes, which provides an insight into the interaction between ACTH
      and inflammatory mediators.

PMID- 17235325
TI  - Characterization of human KAP24.1, a cuticular hair keratin-associated protein
      with unusual amino-acid composition and repeat structure.
AB  - In a search for genes overexpressed in human sexual hairs, several partial
      complementary DNA (cDNA) sequences were isolated. Screening of a human scalp cDNA
      library with one fragment led to the isolation of a full-length cDNA clone, which
      showed identity to another known sequence, termed KAP24-1 (AB09693).
      Bioinformatic analysis revealed that the gene for this cDNA consisted of one exon
      and was located ca. 86 kb away from the chromosome 21q22.1 keratin-associated
      protein (KAP) gene domain. RT-PCR analysis of a variety of organs showed that
      KAP24.1 was only present in human scalp. The KAP24.1 protein consisted of 254
      amino acids, exhibited a high content of serine, proline, and tyrosine, but low
      cysteine content and possessed several carboxyterminal tyrosine-containing tandem
      decameric repeat structures. Evolutionary tree analysis showed no association to
      other KAP family members. In situ hybridization and indirect immunofluorescence
      microscopy studies using an antibody derived from KAP24.1 demonstrated specific
      expression in the middle/upper hair cuticle. The structure of the KRTAP24, its
      proximity to the chromosome 21q22.1 KAP gene domain, the presence of repeat
      motifs in the protein and its localization in the hair cuticle points to KAP24.1
      being a novel human KAP family member.

PMID- 17235326
TI  - Membrane lipid alterations as a possible basis for melanocyte degeneration in
      vitiligo.
AB  - The occurrence of oxidative stress has been proposed as a pathogenetic mechanism
      for melanocyte degeneration in vitiligo. In order to evaluate this possible
      correlation we focused on the lipid component of cell membranes. We observed in
      vitiligo melanocytes, through FACS methods, an increased median fluorescence
      intensity of rhodamine 123 and C11-BODIPY581/591 indicating a spontaneous higher
      production of reactive oxygen species (ROS) and membrane lipoperoxidation,
      associated with an altered pattern of cardiolipin (CL) distribution, defined on
      the basis of the fluorescence pattern after staining with 10-nonyl acridine
      orange. We confirmed membrane peroxidation by confocal and contrast-phase
      microscopes and demonstrated impaired activity of the mitochondrial electron
      transport chain (ETC) complex I. Finally, we observed increased apoptotic events
      following exposure to the pro-oxidant cumene hydroperoxide by Annexin V/propidium
      iodide fluorescence. We hypothesize that in vitiligo melanocytes lipid
      instability, with a defect in the synthesis or recycling of CL, induces ETC
      impairment and ROS production. In basal conditions melanocytes maintain the redox
      balance whereas following chemical or physical stress ROS-mediated membrane
      peroxidation is increased with a possible further CL oxidation, leading to cell
      death or detachment.

PMID- 17235327
TI  - Regulation of IL-13 receptors in human keratinocytes.

PMID- 17235328
TI  - Dimethylfumarate induces immunosuppression via glutathione depletion and
      subsequent induction of heme oxygenase 1.
AB  - A mixture of different fumaric acid esters (FAE) is established for systemic
      therapy of psoriasis, a frequent inflammatory skin disease. The main active
      compound of FAE, however, has not been identified so far, and the mechanisms of
      activity are only partially understood. We analyzed the impact of FAE on in vitro
      immune function and aimed to gain knowledge about the mode of action.
      Dimethylfumarate (DMF) and diethylfumarate (DEF), but not fumaric acid,
      methylhydrogenfumarate and ethylhydrogenfumarate, exhibited potent depression of
      inflammatory cytokine secretion (e.g., tumor necrosis factoralpha, IL-12, and
      IFNgamma) in activated human peripheral blood mononuclear cells. Moreover, solely
      DMF and DEF inhibited alloreactive T-cell proliferation in mixed leukocyte
      reaction. Interestingly, these immunosuppressive effects were accompanied by the
      strong induction of the anti-inflammatory stress protein heme oxygenase 1 (HO-1).
      Supplementation with exogenous glutathione (GSH), which is known to bind DMF,
      prevented both HO-1 induction as well as the anti-inflammatory effects of DMF.
      Moreover, inhibition of HO-1 activity restored the diminished IL-12 and IFNgamma
      production after FAE treatment. These results suggest that DMF acts as active
      compound within the FAE mixture and at least partially mediates its
      immunomodulatory activity by the induction of the anti-inflammatory stress
      protein HO-1 ascribed to the functional depletion of reduced GSH.

PMID- 17235329
TI  - IgE basement membrane zone antibodies induce eosinophil infiltration and
      histological blisters in engrafted human skin on SCID mice.
AB  - Bullous pemphigoid (BP) is characterized by the deposition of IgG in the basement
      membrane zone, infiltration of eosinophils, and blister formation. The purpose of
      this study was to evaluate a potential role of IgE basement membrane antibodies
      in the histological findings of BP. LABD97 is a component of the shed ectodomain
      of bullous pemphigoid antigen 2. We have developed an IgE hybridoma to LABD97
      antigen. This hybridoma was injected subcutaneously in SCID mice with engrafted
      human skin. A subcutaneous hybridoma secreting IgE antibodies developed. An IgE
      mouse hybridoma to trinitrophenyl was used as a control. Human grafts and mouse
      skin were examined grossly over 21 days, histologically, and immunopathologically
      at day 21 after injection of the hybridoma. A visible subcutaneous tumor
      developed in 10-14 days. Erythema and intense scratching developed 2-3 days
      before the tumor in test mice, but not in controls. At day 21, 16/16 test mice
      developed intense eosinophil infiltration and degranulation of the human mast
      cells within the grafts and 13/16 developed histological, but not clinically
      visible, basement membrane blisters. Human skin grafts of control mice and normal
      mouse skin on the test mice and control mice did not develop any histological
      abnormalities. IgE antibodies to LABD97 recapitulate the histological
      inflammatory process seen in BP.

PMID- 17235330
TI  - Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma
      concentrations in HIV-infected individuals.
AB  - To assess the association of CYP2B6 allelic diversity with efavirenz (EFV)
      pharmacokinetics, we performed extensive genotyping of 15 relevant single
      nucleotide polymorphism in 169 study participants, and full resequencing of
      CYP2B6 in individuals with abnormal EFV plasma levels. Seventy-seven (45.5%)
      individuals carried a known (CYP2B6*6, *11, *15, or *18) or new loss/diminished
      function alleles. Resequencing defined two new loss-of-function alleles: allele
      *27 (marked by 593T>C [M198T]), that results in 85% decrease in enzyme activity
      and allele *28 (marked by 1132C>T), that results in protein truncation at
      arginine 378. Median AUC levels were 188.5 microg h/ml for individuals homozygous
      for a loss/diminished-function allele, 58.6 microg h/ml for carriers, and 43.7
      microg h/ml for noncarriers (P<0.0001). Individuals with a poor metabolizer
      genotype had a likelihood ratio of 35 (95% CI, 11-110) of presenting very high
      EFV plasma levels. CYP2B6 poor metabolizer genotypes explain to a large extent
      EFV pharmacokinetics and identify individuals at risk of extremely elevated EFV
      plasma levels.

PMID- 17235331
TI  - Risk of extrapyramidal syndrome in schizophrenic patients treated with
      antipsychotics: a population-based study.
AB  - To compare the prevalence of extrapyramidal syndrome (EPS) between the first
      generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), the
      co-prescribing rate of anti-Parkinson drugs (APDs) of each antipsychotic drug was
      analyzed using population database. Fourteen antipsychotics had been prescribed
      during the 5-year study period. Among the SGAs, quetiapine had the lowest crude
      co-prescribing rate of APDs (27.09%), whereas risperidone had the highest rate
      (66.50%). Among the FGAs, thioridazine and loxapine had the lowest (60.99%) and
      highest rates (96.35%), respectively. The rankings of the co-prescribing rate of
      APDs among antipsychotics, in increasing order, were quetiapine, clozapine,
      olanzapine, thioridazine, zotepine, chlorpromazine, risperidone, sulpiride,
      clotiapine, flupentixol, haloperidol, zuclopentixol, trifluoperazine, and
      loxapine. The results indicate that the risk of EPS appears to be lower in SGAs
      than in FGAs; however, the considerably high rate of EPS in some of the newer
      generation of antipsychotics warrants clinical attention.

PMID- 17235332
TI  - Biomedical communications: collaborative research in scientific visualization,
      online learning, and knowledge translation.
AB  - Collaborative research in biomedical communications investigates the role of
      visual media in scientific discovery and in patient and health professional
      education. The spectrum of work is broad and includes the visualization of
      scientific knowledge and simulation of hypothetical models of health and disease,
      as well as the design of audience-centered interactive visual media. The work
      cited supports the notion that research-based visual media can contribute to the
      core missions of science: discovery, communication, collaboration, and education.

PMID- 17235333
TI  - In vitro-in vivo correlation of hepatobiliary drug clearance in humans.
AB  - The biliary clearance (Cl(biliary)) of three compounds was estimated using
      sandwich-cultured human hepatocytes (SCHH) and compared with Cl(biliary) values
      measured in vivo. Tc-99m sestamibi (MIBI) Cl(biliary) was determined in seven
      healthy volunteers using an oroenteric catheter to aspirate duodenal secretions,
      and gamma scintigraphy to determine gallbladder contraction; this technique was
      used previously to determine Tc-99m mebrofenin (MEB) and piperacillin (PIP) in
      vivo Cl(biliary). In vitro Cl(biliary) of MEB, MIBI, and PIP was quantified in
      SCHH as the ratio of mass excreted into bile canaliculi and area under the blood
      concentration-time curve (AUC) in medium. MIBI Cl(biliary) in vivo was 5.5+/-1.2
      mL/min/kg (mean+/-SD). The rank order of Cl(biliary) predicted from SCHH
      corresponded well with the in vivo Cl(biliary) values in mL/min/kg for MEB (7.44
      vs 16.1), MIBI (1.20 vs 5.51), and PIP (0.028 vs 0.032). In conclusion, the
      methods developed allowed for reproducible quantification of Cl(biliary) of drugs
      in healthy humans and prediction of Cl(biliary) from in vitro data.

PMID- 17235336
TI  - The ivory tower grays.
AB  - The aging of the professoriate has raised questions about how to support
      productive faculty members late in their careers while integrating the vitality
      of youthful scientists.

PMID- 17235334
TI  - Effect of rosiglitazone on visfatin and retinol-binding protein-4 plasma
      concentrations in HIV-positive patients.
AB  - Thiazolidinediones (TZD) may improve insulin resistance in patients with diabetes
      and HIV. The novel adipocytokines visfatin and retinol-binding protein-4 (RBP-4)
      have been proposed to influence the development of impaired glucose tolerance.
      The impact of TZD on these cytokines is yet unknown. In this randomized, double
      blind, placebo-controlled parallel group study, 37 lean HIV-positive subjects
      aged 19-50 years were treated with 8 mg/day rosiglitazone (n=20) or placebo
      (n=17) for 6 months. Insulin sensitivity was estimated from the homeostasis model
      assessment (HOMA) index. Fasting visfatin, RBP-4, leptin, and adiponectin plasma
      concentrations were analyzed by immunoassays. Rosiglitazone had no effect on
      impaired insulin sensitivity, but increased median plasma visfatin from 6.2 ng/ml
      (95% CI: 5.9; 6.5) to 13.7 ng/ml (12.6; 19.1) (P<0.001) and adiponectin from 3.2
      ng/ml (2.2; 4.0) to 4.0 ng/ml (3.3; 8.5; P<0.001). RBP-4 was lowered from 21.0
      ng/ml (19.6; 23.1) to 16.3 ng/ml (15.2; 17.0; P<0.001), and leptin concentrations
      were unchanged. Adipocytokine concentrations were stable in subjects receiving
      placebo, where a deterioration in insulin sensitivity was detectable (P<0.05).
      Changes in visfatin and RBP-4 were correlated in subjects receiving rosiglitazone
      (r=-0.64, P<0.01) but not placebo (r=0.12, P=0.15). TZD treatment affects
      circulating adipocytokine concentrations in subjects with HIV. Reductions in RBP
      4 and increases in visfatin may contribute to the pharmacodynamic action of TZD
      on glucose homeostasis. Quantification of adipocytokines might be useful to
      assess TZD treatment effectiveness in insulin-resistant subjects with HIV.

PMID- 17235337
TI  - The model student: what chemical model systems can teach us about biology.
AB  - Model systems have evolved with the times, making use of modern biological
      methods and incorporating biological complexity. This evolution has increased the
      relevance of models as tools for studying biology.

PMID- 17235338
TI  - Emerging glycomics technologies.
AB  - The nascent field of glycomics is currently undergoing rapid development, largely
      as a result of advances in technologies for analyzing glycan structure,
      unraveling glycan-protein interactions and establishing the functional
      significance of glycans. A meeting was held in November 2006 to explore the
      challenges and opportunities ahead for this emerging 'omics' domain.

PMID- 17235339
TI  - Molecular frontiers.

PMID- 17235340
TI  - The microtubule-pore gatekeeper.

PMID- 17235341
TI  - A shortcut to peptides to modulate platelets.

PMID- 17235342
TI  - Getting into the fold.

PMID- 17235343
TI  - The most versatile of all reactive intermediates?

PMID- 17235344
TI  - Success in tubulysin D synthesis.

PMID- 17235345
TI  - An RNA transcriptional regulator templates its own regulatory RNA.

PMID- 17235347
TI  - Imaging single events at the cell membrane.
AB  - The ability to sense and respond to the environment is a hallmark of living
      systems. These processes occur at the levels of the organism, cells and
      individual molecules. Sensing of extracellular changes could result in a
      structural or chemical alteration in a molecule, which could in turn trigger a
      cascade of intracellular signals or regulated trafficking of molecules at the
      cell surface. These and other such processes allow cells to sense and respond to
      environmental changes. Often, these changes and the responses to them are
      spatially and/or temporally localized, and visualization of such events
      necessitates the use of high-resolution imaging approaches. Here we discuss
      optical imaging approaches and tools for imaging individual events at the cell
      surface with improved speed and resolution.

PMID- 17235350
TI  - PKC-beta II expression has prognostic impact in nodal diffuse large B-cell
      lymphoma.
AB  - Recent studies of gene expression and immunohistochemistry have shown that
      protein kinase C-beta II (PKC-beta II) might have prognostic significance in
      patients with diffuse large B-cell lymphoma (DLBCL). We sought to determine the
      prognostic significance of the expression of PKC-beta II in patients with nodal
      DLBCL. Formalin-fixed, paraffin-embedded tissues were stained with a monoclonal
      antibody to PKC-beta II protein. A total of 125 patients were studied; 83
      patients (66%) were in the low-risk International Prognostic Index (IPI) group.
      Forty-eight patients (38%) were positive for PKC-beta II. Complete remission was
      obtained in 70%, and was not influenced by the PKC-beta II status (67 vs 71%).
      The 5-year event-free survival (EFS) was worse in high-risk patients (14 vs 58%,
      P<0.001) and in those with PKC-beta II positivity (36 vs 49%, P=0.054). In low
      risk IPI patients, PKC-beta II expression was related to a worse 5-year overall
      survival (OS) (60 vs 76%, P=0.033) and a worse 5-year EFS (48 vs 66%, P=0.014).
      In a Cox regression analysis for EFS, both PKC-beta II expression (hazard
      ratio=1.68, P=0.037) and the IPI (HR=3.07, P<0.001) were independent poor
      prognostic factors. PKC-beta II (HR=1.72, P=0.046) and the IPI (HR=5.16, P<0.001)
      were also independent poor prognostic factors for the OS. PKC-beta II expression,
      along with the IPI, were associated with a worse EFS and OS in patients with
      nodal DLBCL specially in low-risk IPI patients.

PMID- 17235351
TI  - Mapping of angiogenic markers for targeting of vectors to tumor vascular
      endothelial cells.
AB  - The vasculature of mouse breast tumor spheroids grown on mammary fat pad tissue
      in an intravital microscopy (IVM) viewing chamber was shown to derive from
      infiltrating angiogenic mammary vessels. The receptors tissue factor (TF), alpha
      V beta 3 integrin and Tie-2 were expressed on the vascular endothelium in the
      periphery but not in the center of the tumor spheroids nor in the mammary tissue
      nor in smooth muscle tissue, whereas Tie-1 and PCAM-1 were expressed extensively
      in the entire tumor and in the vascular endothelium of the entire tumor nodule
      and in normal mammary tissue. TF is a specific target for adenoviral vector
      mediated cancer immunotherapy. Subcutaneous injection of the AdfVII/IgG(1)Fc
      vector leads to the release into the system circulation of a fVII/IgG(1)Fc
      immunoconjugate molecule that binds specifically and tightly to TF on vascular
      endothelial cells and tumor cells, activating a cytolytic immune response against
      the targeted cells. We show that a single administration of the AdfVII/IgG(1)Fc
      vector destroys the peripheral but not the central vasculature of a tumor
      spheroid, causing partial tumor regression; additional administrations prevent
      regeneration of the peripheral vasculature and regrowth of the tumor. These
      findings indicate that a critical parameter for optimizing tumor damage is the
      schedule for successive administrations of the AdfVII/IgG(1)Fc, which should
      coincide with the regeneration of the peripheral vasculature and continue until
      the tumor is destroyed.

PMID- 17235352
TI  - The proteasome inhibitor bortezomib acts differently in combination with p53 gene
      transfer or cytotoxic chemotherapy on NSCLC cells.
AB  - In this report, the effects of a combined treatment with the proteasome inhibitor
      bortezomib and either a recombinant adeno-associated virus type 2 (rAAV-2)
      mediated p53 gene transfer or chemotherapeutic agents, docetaxel and pemetrexed,
      were tested on p53 positive and p53negative non-small cell lung cancer (NSCLC)
      cell lines. The combination of bortezomib and rAAV-p53 led to a significant
      synergistic inhibition of cell growth between 62-82% depending on the p53 status
      of the cell line and drug concentration. Surviving cells of the combined
      treatment showed a significant reduced ability to form colonies. Enhanced cell
      toxicity was associated with a 5.3-14.4-fold increase of the apoptotic rate and
      intracellular p53 level up to 50.4% following vector-mediated p53 restoration and
      bortezomib treatment. In contrast, an antagonistic effect on tumor cell growth
      and colony formation was observed for the combination of bortezomib and docetaxel
      or pemetrexed as a reduction of cell growth between 31 and 48% was found in
      comparison to 50% using the single agents. Lower cytotoxic effects were
      associated with significantly reduced apoptosis and an increase of clonogenic
      growth. The observed antagonistic effects between bortezomib and docetaxel or
      pemetrexed might influence clinical trials using these compounds. Conversely, p53
      restoration and bortezomib treatment led to enhanced, synergistic tumor cell
      toxicity.

PMID- 17235353
TI  - A three-dimensional assay for measurement of viral-induced oncolysis.
AB  - Oncolytic viruses represent a novel cancer treatment strategy. Despite their
      promising preclinical data, however, corresponding clinical trials have
      disappointed. To aid preclinical analyses, we hypothesized that three-dimensional
      tumor cell clusters or spheroids might provide an assay system superior to
      conventional monolayer cell cultures. Spheroids show viral infection, replication
      and oncolytic patterns distinct from conventional monolayer assays. Therefore,
      viral tumor penetration and oncolysis measurements may be improved with such
      three-dimensional models. Also, preclinical analyses of oncolytic viruses
      frequently measure mitochondrial activity, but more accurate measures of
      oncolysis might involve quantitation of intracellular protein release. Therefore,
      we measured luciferase released from luciferase-expressing spheroids and found
      unique patterns that maintained consistency with various viruses and doses. The
      relative variations between viruses and doses may represent temporal differences
      in oncolysis dynamics. Analysis of five recombinant replicative adenoviruses with
      promise for clinical application showed that Ad5/3-Delta24 produced the most
      luciferase release 1 week after infection and achieved the earliest and highest
      peak luciferase release level. Ad5/3-Delta24 also effected the earliest subtotal
      spheroid cell death. These findings closely parallel monolayer oncolysis assays
      with these agents. Therefore, the luciferase-expressing tumor spheroid assay
      represents a promising three-dimensional model for preclinical analysis of
      replicative oncolytic agents.

PMID- 17235354
TI  - Enhanced T-cell immunity induced by dendritic cells with phagocytosis of heat
      shock protein 70 gene-transfected tumor cells in early phase of apoptosis.
AB  - The dual role of heat shock protein 70 (HSP70), as antigenic peptide chaperone
      and danger signal, makes it especially important in dendritic cell (DC)-based
      vaccination. In this study, we investigated the impacts of apoptotic transgenic
      MCA/HSP tumor cells expressing HSP70 on DC maturation, T-cell stimulation and
      vaccine efficacy. We found that DCs with phagocytosis of MCA/HSP in early phase
      of apoptosis expressed more pMHC I complexes, stimulated stronger cytotoxic T
      lymphocyte (CTL) responses (40% specific killing at an E:T cell ratio of 50) and
      induced immune protection in 90% of mice against MCA tumor cell challenge,
      compared with 25% specific CTL killing activity and 60% immune protection seen in
      mice immunized with DC with phagocytosis of MCA/HSP in late phase of apoptosis
      (P<0.05). Similar results were confirmed in another EG7 tumor model also
      expressing HSP70. Taken together, our data demonstrate that HSP70 on apoptotic
      tumor cells stimulate DC maturation, and DC with phagocytosis of apoptotic tumor
      cells expressing HSP70 in early phase of apoptosis more efficiently induced tumor
      specific CTL responses and immunity than DCs with phagocytosis of apoptotic tumor
      cells in late phase of apoptosis. These results may have an important impact in
      designing DC-based antitumor vaccines.

PMID- 17235355
TI  - Incorporation of a laminin-derived peptide (SIKVAV) on polymer-modified
      adenovirus permits tumor-specific targeting via alpha6-integrins.
AB  - Effective gene therapy for disseminated metastatic cancer is currently impossible
      because of poor delivery of vector to target sites. Modification of viral vectors
      to target advanced cancer has long been a challenge. In this study, we aimed to
      redirect adenovirus tropism to infect prostate cancer cells via alpha6beta1
      integrins, whose expression is upregulated during prostate cancer progression. To
      ablate normal mechanisms of infection and provide a framework for attachment of
      targeting ligands, viruses were non-genetically modified with pHPMA-ONp polymer.
      Addition of polymer-coated virus to prostate cells showed significantly reduced
      transgene expression compared with unmodified virus. To restore infectivity, an
      alpha6-integrin binding peptide (-SIKVAV-) derived from laminin was incorporated
      onto the surface of the polymer-coated viruses. Photon correlation spectroscopic
      analysis revealed a small increase in the mean diameter of the particles
      following retargeting. Addition of -SIKVAV- peptide restored virus infectivity of
      PC-3 cells in a ligand concentration-dependent manner that was significantly
      improved following removal of unincorporated polymer and peptide. Competition
      assays using cells preincubated with Ad5 fiber protein or free -SIKVAV- peptide
      confirmed that entry of retargeted viruses was mediated via the incorporated
      ligand. Application of retargeted viruses to a panel of human cell lines revealed
      varying levels of transduction efficiency. Flow cytometric analysis of cells
      using anti-alpha6 integrin and anti-beta1 integrin antibodies demonstrated that
      for prostate cells, greater transduction efficiency correlated with higher levels
      of expression of both integrin subunits. Furthermore with the exception of LNCaP
      cells, increased alpha6beta1 integrin expression correlated with advanced
      disease. Intravenous administration of retargeted viruses to tumor-bearing mice
      resulted in slower plasma clearance and greatly reduced liver tropism, and hence
      toxicity compared with unmodified virus, while maintaining reporter gene
      expression in the tumor. The data suggest that YESIKVAVS-retargeted viruses have
      potential for systemic delivery for the treatment of metastatic disease.

PMID- 17235356
TI  - Spleen but not tumor infiltration by dendritic and T cells is increased by
      intravenous adenovirus-Flt3 ligand injection.
AB  - Dendritic cell (DC) expansion is regulated by the hematopoietic growth factor fms
      like tyrosine kinase 3 ligand (Flt3L). DCs are critical to the control of tumor
      growth and metastasis, and there is a positive correlation between intratumoral
      DC infiltration and clinical outcome. In this report, we first demonstrate that
      single intravenous (i.v.) injections of adenovirus (Adv)-Flt3L significantly
      increased splenic dendritic, B, T and natural killer (NK) cell numbers in both
      normal and mammary tumor-bearing mice. In contrast, the numbers of DCs and T
      cells infiltrating the tumors were not increased. Consistent with the minimal
      effect on immune cell infiltration, i.v. Adv-Flt3L injections had no therapeutic
      activity against orthotopic mammary tumors. In addition, we noted tumor and Adv
      Flt3L expansion of Gr1(+)CD11b(+) immature myeloid suppressor cells (IMSCs),
      which may inhibit the therapeutic efficacy of Adv-Flt3L-expanded DCs.

PMID- 17235357
TI  - PATJ regulates directional migration of mammalian epithelial cells.
AB  - Directional migration is important in wound healing by epithelial cells. Recent
      studies have shown that polarity proteins such as mammalian Partitioning
      defective 6 (Par6), atypical protein kinase C (aPKC) and mammalian Discs large 1
      (Dlg1) are crucial not only for epithelial apico-basal polarity, but also for
      directional movement. Here, we show that the protein associated with Lin seven 1
      (PALS1)-associated tight junction protein (PATJ), another evolutionarily
      conserved polarity protein, is also required for directional migration by using a
      wound-induced migration assay. In addition, we found that aPKC and Par3 localize
      to the leading edge during migration of epithelia and that PATJ regulates their
      localization. Furthermore, our results show that microtubule-organizing centre
      orientation is disrupted in PATJ RNA interference (RNAi) MDCKII (Madin-Darby
      canine kidney II) cells during migration. Together, our data indicate that PATJ
      controls directional migration by regulating the localization of aPKC and Par3 to
      the leading edge. The migration defect in PATJ RNAi cells seems to be due to the
      disorganization of the microtubule network induced by mislocalization of polarity
      proteins.

PMID- 17235358
TI  - MEL-28/ELYS is required for the recruitment of nucleoporins to chromatin and
      postmitotic nuclear pore complex assembly.
AB  - The metazoan nuclear envelope (NE) breaks down and re-forms during each cell
      cycle. Nuclear pore complexes (NPCs), which allow nucleocytoplasmic transport
      during interphase, assemble into the re-forming NE at the end of mitosis. Using
      in vitro NE assembly, we show that the vertebrate homologue of MEL-28 (maternal
      effect lethal), a recently discovered NE component in Caenorhabditis elegans,
      functions in postmitotic NPC assembly. MEL-28 interacts with the Nup107-160
      complex (Nup for nucleoporin), an important building block of the NPC, and is
      essential for the recruitment of the Nup107-160 complex to chromatin. We suggest
      that MEL-28 acts as a seeding point for NPC assembly.

PMID- 17235361
TI  - Verifiable CPD paper: oral health of remand prisoners in HMP Brixton, London.
AB  - OVERVIEW: This study investigated the general and oral health status and
      behaviours and the dental treatment requirements of remand prisoners. It makes
      recommendations on how their oral health care needs may be met. METHOD: A
      convenience sample of 78 remand prisoners participated in the study within HMP
      Brixton. The study involved a structured interview, to establish health status
      and behaviours as well as perceived oral health needs, combined with an oral
      examination to establish normative treatment need. RESULTS: Prisoners' general
      health was compromised. In particular, there were high levels of mental illness
      and infectious disease. Unhealthy behaviours such as tobacco smoking, alcohol
      use, drug dependency, and high sugar diets were commonplace. This affected the
      remand prisoners' oral health, which presented with high levels of decay and
      relatively low levels of both missing and filled teeth. Whilst prisoners made
      high use of prison dental services, they made little use of dental services
      outside of prison. The high turnover of remand prisoners and high demand for
      emergency care made the delivery of preventive and routine care difficult.
      CONCLUSION: Remand prisoners have compromised general and oral health compared
      with the general population. They exhibit poor oral health, which is contributed
      to by their lifestyles and health behaviours.

PMID- 17235359
TI  - The SM protein VPS-45 is required for RAB-5-dependent endocytic transport in
      Caenorhabditis elegans.
AB  - Rab5, a small guanosine triphosphatase, is known to regulate the tethering and
      docking reaction leading to SNARE (soluble NSF attachment protein receptors)
      mediated fusion between endosomes. However, it is uncertain how the signal of the
      activated Rab5 protein is transduced by its downstream effectors during endosome
      fusion. Here, we show that the Sec1/Munc18 gene vps-45 is essential for not only
      viability and development but also receptor-mediated and fluid-phase endocytosis
      pathways in Caenorhabditis elegans. We found that VPS-45 interacts with a Rab5
      effector, Rabenosyn-5 (RABS-5), and the mutants of both vps-45 and rabs-5 show
      similar endocytic phenotypes. In the macrophage-like cells of vps-45 and rabs-5
      mutants, aberrantly small endosomes were accumulated, and the endosome fusion
      stimulated by the mutant RAB-5 (Q78L) is suppressed by these mutations. Our
      results indicate that VPS-45 is a key molecule that functions downstream from RAB
      5, cooperating with RABS-5, to regulate the dynamics of the endocytic system in
      multicellular organisms.

PMID- 17235362
TI  - Oral and salivary changes in patients with end stage renal disease (ESRD): a two
      year follow-up study.
AB  - OBJECTIVES: To compare oral health, salivary flow rate, xerostomia and thirst in
      end stage renal disease (ESRD) patients remaining on dialysis treatment and after
      renal transplantation. DESIGN: Longitudinal observation. SETTING: ESRD patients
      recruited from dialysis centres in Amsterdam, The Hague and Utrecht, The
      Netherlands. METHOD: At baseline and after two years, salivary flow rates,
      xerostomia and thirst were determined in 43 ESRD patients. The number of decayed
      missing filled teeth/surfaces (DMFT/DMFS) was recorded, and periodontal status
      assessed. RESULTS: After renal transplantation (n = 20), the salivary flow rate
      increased significantly from UWS = 0.30 +/- 0.21 ml/min to 0.44 +/- 0.29 ml/min
      (p <0.001) and the level of xerostomia and thirst decreased. After two years, the
      percentage of bleeding on probing in dialysis patients (n = 23) decreased from
      29.5 +/- 25.4% to 10.3 +/- 12.3%, (p <0.05). No differences in DMFT and DMFS were
      observed between dialysis and renal transplant patients. CONCLUSIONS: DMFT,
      dental plaque, gingival bleeding and periodontal indices did not change
      remarkably after two years, comparing dialysis and renal transplant patients.
      Renal transplantation enhances salivary flow and decreases symptoms of xerostomia
      and thirst, and hence enhances the potential to improve the quality of life of
      affected individuals.

PMID- 17235364
TI  - WHO BENEFITS MOST FROM A BROADLY TARGETED PREVENTION PROGRAM? DIFFERENTIAL
      EFFICACY ACROSS POPULATIONS IN THE TEEN OUTREACH PROGRAM.
AB  - This study examined a highly successful, well-documented, national program to
      prevent teenage pregnancy and school failure-the Teen Outreach program-to address
      a fundamental question: How well can a developmentally focused, broadly targeted
      prevention program address the needs of those students within the program who are
      at the highest risk of problematic behavior. The hypothesis that the
      developmental focus of a broadly targeted intervention would lead it to have
      greater program efficacy among those young people who began the program at
      greatest risk was examined with multisite data collected on more than 3,300 Teen
      Outreach and comparison group students. Results confirmed prior findings
      regarding the overall efficacy of the Teen Outreach program, and indicated that
      the program appeared most effective for those students at greatest initial risk
      of the problem behaviors being targeted. Implications for the targeting of the
      Teen Outreach program specifically and of similar primary prevention programs
      more generally are discussed.

PMID- 17235365
TI  - Perceptual image quality: Effects of tone characteristics.
AB  - Tone mapping refers to the conversion of luminance values recorded by a digital
      camera or other acquisition device, to the luminance levels available from an
      output device, such as a monitor or a printer. Tone mapping can improve the
      appearance of rendered images. Although there are a variety of algorithms
      available, there is little information about the image tone characteristics that
      produce pleasing images. We devised an experiment where preferences for images
      with different tone characteristics were measured. The results indicate that
      there is a systematic relation between image tone characteristics and perceptual
      image quality for images containing faces. For these images, a mean face
      luminance level of 46-49 CIELAB L* units and a luminance standard deviation
      (taken over the whole image) of 18 CIELAB L* units produced the best renderings.
      This information is relevant for the design of tone-mapping algorithms,
      particularly as many images taken by digital camera users include faces.

PMID- 17235363
TI  - Toxicity assays in nanodrops combining bioassay and morphometric endpoints.
AB  - BACKGROUND: Improved chemical hazard management such as REACH policy objective as
      well as drug ADMETOX prediction, while limiting the extent of animal testing,
      requires the development of increasingly high throughput as well as highly
      pertinent in vitro toxicity assays. METHODOLOGY: This report describes a new in
      vitro method for toxicity testing, combining cell-based assays in nanodrop Cell
      on-Chip format with the use of a genetically engineered stress sensitive hepatic
      cell line. We tested the behavior of a stress inducible fluorescent HepG2 model
      in which Heat Shock Protein promoters controlled Enhanced-Green Fluorescent
      Protein expression upon exposure to Cadmium Chloride (CdCl2), Sodium Arsenate
      (NaAsO2) and Paraquat. In agreement with previous studies based on a micro-well
      format, we could observe a chemical-specific response, identified through
      differences in dynamics and amplitude. We especially determined IC50 values for
      CdCl2 and NaAsO2, in agreement with published data. Individual cell
      identification via image-based screening allowed us to perform multiparametric
      analyses. CONCLUSIONS: Using pre/sub lethal cell stress instead of cell
      mortality, we highlighted the high significance and the superior sensitivity of
      both stress promoter activation reporting and cell morphology parameters in
      measuring the cell response to a toxicant. These results demonstrate the first
      generation of high-throughput and high-content assays, capable of assessing
      chemical hazards in vitro within the REACH policy framework.

PMID- 17235366
TI  - Optical-CT imaging of complex 3D dose distributions.
AB  - The limitations of conventional dosimeters restrict the comprehensiveness of
      verification that can be performed for advanced radiation treatments presenting
      an immediate and substantial problem for clinics attempting to implement these
      techniques. In essence, the rapid advances in the technology of radiation
      delivery have not been paralleled by corresponding advances in the ability to
      verify these treatments. Optical-CT gel-dosimetry is a relatively new technique
      with potential to address this imbalance by providing high resolution 3D dose
      maps in polymer and radiochromic gel dosimeters. We have constructed a 1(st)
      generation optical-CT scanner capable of high resolution 3D dosimetry and applied
      it to a number of simple and increasingly complex dose distributions including
      intensity-modulated-radiation-therapy (IMRT). Prior to application to IMRT, the
      robustness of optical-CT gel dosimetry was investigated on geometry and variable
      attenuation phantoms. Physical techniques and image processing methods were
      developed to minimize deleterious effects of refraction, reflection, and
      scattered laser light. Here we present results of investigations into achieving
      accurate high-resolution 3D dosimetry with optical-CT, and show clinical examples
      of 3D IMRT dosimetry verification. In conclusion, optical-CT gel dosimetry can
      provide high resolution 3D dose maps that greatly facilitate comprehensive
      verification of complex 3D radiation treatments. Good agreement was observed at
      high dose levels (>50%) between planned and measured dose distributions. Some
      systematic discrepancies were observed however (rms discrepancy 3% at high dose
      levels) indicating further work is required to eliminate confounding factors
      presently compromising the accuracy of optical-CT 3D gel-dosimetry.

PMID- 17235367
TI  - Phrenic nerve injury after catheter ablation of atrial fibrillation.
AB  - Phrenic Nerve Injury (PNI) has been well studied by cardiac surgeons. More
      recently it has been recognized as a potential complication of catheter ablation
      with a prevalence of 0.11 to 0.48 % after atrial fibrillation (AF) ablation. This
      review will focus on PNI after AF ablation. Anatomical studies have shown a close
      relationship between the right phrenic nerve and it's proximity to the superior
      vena cava (SVC), and the antero-inferior part of the right superior pulmonary
      vein (RSPV). In addition, the proximity of the left phrenic nerve to the left
      atrial appendage has been well established. Independent of the type of ablation
      catheter (4 mm, 8 mm, irrigated tip, balloon) or energy source used
      (radiofrequency (RF), ultrasound, cryothermia, and laser); the risk of PNI exists
      during ablation at the critical areas listed above. Although up to thirty-one
      percent of patients with PNI after AF ablation remain asymptomatic, dyspnea
      remain the cardinal symptom and is present in all symptomatic patients. Despite
      the theoretical risk for significant adverse effect on functional status and
      quality of life, short-term outcomes from published studies appear favorable with
      81% of patients with PNI having a complete recovery after 7 +/- 7 months.
      CONCLUSION: Existing studies have described PNI as an uncommon but avoidable
      complication in patients undergoing pulmonary vein isolation for AF. Prior to
      ablation at the SVC, antero-inferior RSPV ostium or the left atrial appendage,
      pacing should be performed before energy delivery. If phrenic nerve capture is
      documented, energy delivery should be avoided at this site. Electrophysiologist's
      vigilance as well as pacing prior to ablation at high risk sites in close
      proximity to the phrenic nerve are the currently available tools to avoid the
      complication of PNI.

PMID- 17235369
TI  - Early risk stratification for arrhythmic death in patients with ST-elevation
      myocardial infarction.
AB  - BACKGROUND: Sudden cardiac death is a leading cause of death in patients with ST
      elevation myocardial infarction (MI). According to high cost of modern
      therapeutic modalities it is of paramount importance to define protocols for risk
      stratification of post-MI patients before considering expensive devices such as
      implantable cardioverter-defibrillator. METHODS: One hundred and thirty seven
      patients with acute ST-elevation MI were selected and underwent echocardiographic
      study, holter monitoring and signal-averaged electrocardiography (SAECG). Then,
      the patients were followed for 12 +/-3 months. RESULTS: During follow-up, 13
      deaths (9.5%) occurred; nine cases happened as sudden cardiac death (6.6%). The
      effect of ejection fraction (EF) less than 40% on occurrence of arrhythmic events
      was significant (P<0.001). Sensitivity and positive predictive value of EF<40%
      was 100% and 76.95% respectively. Although with lesser sensitivity and predictive
      power than EF<40%, abnormal heart rate variability (HRV) and SAECG had also
      significant effects on occurrence of sudden death (P=0.02 and P=0.003
      respectively). Nonsustained ventricular tachycardia was not significantly related
      to risk of sudden death in this study (P=0.20). CONCLUSION: This study indicated
      that EF less than 40% is the most powerful predictor of sudden cardiac death in
      post MI patients. Abnormal HRV and SAECG are also important predictors and can be
      added to EF for better risk stratification.

PMID- 17235368
TI  - P-wave duration and dispersion in patients with peripheral edema and its
      amelioration.
AB  - BACKGROUND: Attenuation of the P-wave amplitudes in patients with peripheral
      edema (PERED) has been recently reported, with P-waves regaining some of their
      amplitude in patients, who subsequently experienced amelioration of their PERED.
      Changes in the P-waves correlated with the corresponding alterations in the QRS
      complexes. Also since amplitudes and durations of QRS complexes changed in
      parallel in patients with PERED, it was hypothesized that similar changes in the
      P-wave amplitudes, mean P-wave duration (P-du-mean), and P-wave dispersion (P-d),
      would occur in such patients. METHODS: Measurements of P-wave amplitude, P-du
      mean and P-d in patients who developed, or experienced alleviation, of PERED,
      were carried out and analyzed. RESULTS: Although P-wave amplitudes and P-wave
      areas decreased with development of PERED (N = 16), and increased with its
      amelioration (N = 6), P-dur-mean before PERED was 66.8+/-14.5 ms, and at peak
      weight gain it was 65.2+/-11.9 ms, p = 0.66; also at peak weight gain and
      subsequent lowest weight, in the patients who lost weight, it was 66.5+/-9.9 ms
      and 72.3+/-12.0 ms, respectively, p = 0.38. Similarly the P-d prior to PERED was
      62.3+/-25.2 ms, and at peak weight gain it was 74.3+/-29.3 ms, p = 0.09; also at
      peak weight and subsequent lowest weight, in the patients who lost weight, it was
      58.8+/-34.2 ms, and 61.3+/-13.6 ms, respectively, p = 0.87. CONCLUSION: P-du-mean
      and P-d did not change in patients who developed PERED; their stability is
      attributed to the offsetting of the electrophysiologically-mediated real changes,
      by opposite apparent changes, imparted by PERED.

PMID- 17235370
TI  - Comparison of the electrocardiographic features of complete left bundle branch
      block in patients with ischemic and nonischemic left ventricular dysfunction.
AB  - BACKGROUND: Differentiating ischemic (ILVD) from nonischemic left ventricular
      dysfunction (NILVD) is important prognostically and therapeutically but might be
      difficult clinically. The differentiating role of electrocardiographic (ECG)
      features in the presence of left bundle-branch block (LBBB) is debatable on
      differentiating ILVD from NILVD. OBJECTIVE: The present study assessed whether
      there is the role of certain ECG features in differentiating ILVD from NILVD in
      the presence of the complete LBBB. METHODS AND RESULTS: Patients who had LBBB
      were divided into two groups based on the presence and type of left ventricular
      dysfunction; (1) ILVD group (49 patients; 20 female; age: 65 +/- 11 years) and
      (2) NILVD group (49 patients; 22 female; age: 59 +/- 12 years), and numerous ECG
      features were compared. Most of these ECG features did not show any difference
      between the groups except for following ECG findings; the voltage of R wave in V6
      were statistically higher in NILVD group compared ILVD group (p: 0.03); the
      depression of the ST-J point by more than 0.2 mV in V6 were also frequently
      observed in NILVD group compared ILVD group (5/ 10% vs 19/ 39% , p: 0.001); and
      the notching in the ascending or descending limb of the S wave in V1-4 leads were
      more in ILVD group (18/ 36% vs 8/ 16% p: 0.03; 9/ 16% vs 2/ 4%, p: 0.03,
      respectively). CONCLUSION: In the current study, although some ECG findings were
      found to be useful, ECG features in the presence of complete LBBB had poor value
      in differentiating ILVD from NILVD.

PMID- 17235371
TI  - Mid-term follow-up of patients with Brugada syndrome following a cardioverter
      defibrillator implantation: a single center experience.
AB  - BACKGROUND: Brugada syndrome is an arrhythmogenic disease characterized by an ECG
      pattern of ST-segment elevation in the right precordial leads and an increase
      risk of sudden cardiac death. Risk stratification for the life-threatening
      arrhythmic events in Brugada syndrome is not yet established. In the present
      study, we report our experience in patients with Brugada syndrome, following an
      ICD implantation. METHODS AND RESULTS: A total of 12 patients (11 men, 1 woman)
      with a mean age of 46.5+/-11.8 were studied. At diagnosis, 7 patients had syncope
      of unknown origin, 2 patients were asymptomatic, 2 patients were survivors of
      cardiac arrest, and 1 had documented clinical VT requiring direct cardioversion
      for termination. Age was similar between the symptomatic and asymptomatic
      patients (46.6+/-13 vs. 46+/-2.8, respectively). Two patients reported a family
      history of sudden cardiac death. In 3 patients, spontaneous coved-type ECG was
      found at baseline. In 9 patients, a class I antiarrhythmic drug administration
      unmasked the characteristic type I ECG. In 4 patients (2 symptomatic with syncope
      at presentation and 2 asymptomatic), who underwent PES, sustained polymorphic VT
      or VF was induced. VF was induced by single extrastimuli in 2 symptomatic
      patients (1 from RV apex and 1 from RVOT). In 2 asymptomatic patients, VF was
      induced by two and triple ventricular extrastimli (1 from RV apex and 1 from
      RVOT). None of them experienced an event during follow-up. No significant
      difference was found between symptomatic and asymptomatic patients (p=NS). The
      mean follow-up period for the entire study population was 27.83+/-11.25 months.
      During follow-up, 2 patients (one with prior cardiac arrest and another with
      syncope) had VF. Both of them had a type I ECG after provocation with a class I
      antiarrhythmic drug. None of them had undergone programmed ventricular
      stimulation. Five patients (41.7 %) had inappropriate ICD interventions during
      follow-up. The cause of inappropriate therapy was sinus tachycardia in 2
      patients, AF in 2 patients and T wave oversensing in 1 patient. CONCLUSION:
      Knowledge about Brugada syndrome is steadily progressing but there are still
      unanswered issues dealing with the risk stratification and the management of
      patients.

PMID- 17235372
TI  - A review of temporary cardiac pacing wires.
AB  - AIMS: This review aims to tabulate data from all available studies of temporary
      cardiac pacing wires. Particular aims were to determine the best route of venous
      access and find ways to reduce complications. The review set out to see if
      specialist doctors are better at inserting wires than non-specialist doctors. In
      addition, a contemporary study of wire insertion has been performed to compare
      modern practice in the UK with the previous studies. METHODS: A literature search
      produced 15 studies available for inclusion. Over 3700 patients from 1973 to 2004
      were included. The data was tabulated and attention was given to the route of
      venous access, the complication rates and whether a specialist or non-specialist
      doctor had inserted the wire. RESULTS: Internal jugular veins are associated with
      lowest complication rates and ease of access. Antecubital fossa veins have the
      highest complication rates. Complication rates are high, especially infections
      and failure to secure access. Specialist doctors have lower rates of
      complications than non-specialist doctors. Elderly patient suffer the highest
      complication rate. Our study showed comparable results to the previous studies.
      CONCLUSION: Internal jugular veins are the preferred route for access followed by
      subclavian and femoral veins. The right side should be used when possible. The
      use of antibiotics and ultrasound probes must be contemplated for all wire
      insertions. Alternatives to wire insertion (especially in the elderly) must be
      seriously considered. Setting up an on-call rota would provide experienced
      doctors to reduce complication rates.

PMID- 17235374
TI  - Exercise testing score for myocardial ischemia gradation.

PMID- 17235373
TI  - Atrial fibrillation and revascularization procedures: clinical and prognostic
      significance. Incidence, predictors, treatment, and long-term outcome.

PMID- 17235375
TI  - Modulation of the complement system by human beta-defensin 2.
AB  - OBJECTIVE: Human beta-defensin (HBD) and the complement system are two important
      innate immune mechanisms active against a broad range of burn and wound
      pathogens. However, excessive or uncontrolled complement activation, following
      thermal injury, contributes to tissue damage. Previous studies from our
      laboratory suggested a decreased expression of HBD-2 in burn wounds and its
      absence in burn blister fluid. Prior studies have demonstrated that human
      neutrophil peptide can bind to the C1q component of the complement system and
      prevent complement activation. The objective of this study was to determine
      whether HBD-1 and HBD-2 can also bind to the C1q component and modulate
      complement activity. METHODS: The binding efficiency of HBD-1 and HBD-2 to the
      C1q component was determined by utilizing dot blot hybridization. The effect of
      HBD-2 on the activation of the complement system by the classical and alternative
      pathways was determined by CH50 and AP50 assays. In addition, the ability of HBD
      1 and HBD-2 to inhibit C1q activity was predicted by a comparison with known C1q
      inhibitor peptide 2J in a DNAStar computer modeling study. RESULTS: C1q binding
      to HBD-2 was strong, whereas C1q binding to HBD-1 was weak. HBD-2 inhibits the
      classical pathway significantly without affecting the alternative pathway. In
      addition, a computer modeling study also revealed structural homology of HBD-2
      with known C1q inhibitory sequences of HBD-2. CONCLUSION: HBD-2 inhibits the
      classical pathway. The replacement of missing defensin, a natural inhibitor of
      the complement system, may have a dual protective role not only as an
      antimicrobial agent but also in providing protection against uncontrolled
      activation of the complement system.

PMID- 17235377
TI  - Vibrational Relaxation in beta-Carotene Probed by Picosecond Stokes and Anti
      Stokes Resonance Raman Spectroscopy.
AB  - Picosecond time-resolved Stokes and anti-Stokes resonance Raman spectra of all
      trans-beta-carotene are obtained and analyzed to reveal the dynamics of excited
      state (S(1)) population and decay, as well as ground-state vibrational
      relaxation. Time-resolved Stokes spectra show that the ground state recovers with
      a 12.6 ps time constant, in agreement with the observed decay of the unique S(1)
      Stokes bands. The anti-Stokes spectra exhibit no peaks attributable to the S(1)
      (2A(g) (-)) state, indicating that vibrational relaxation in S(1) must be nearly
      complete within 2 ps. After photoexcitation there is a large increase in anti
      Stokes scattering from ground-state modes that are vibrationally excited through
      internal conversion. The anti-Stokes data are fit to a kinetic scheme in which
      the C=C mode relaxes in 0.7 ps, the C-C mode relaxes in 5.4 ps and the C-CH(3)
      mode relaxes in 12.1 ps. These results are consistent with a model for S(1)-S(0)
      internal conversion in which the C=C mode is the primary acceptor, the C-C mode
      is a minor acceptor, and the C-CH(3) mode is excited via intramolecular
      vibrational energy redistribution.

PMID- 17235376
TI  - Heroin-Induces Differential Protein Expression by Normal Human Astrocytes (NHA).
AB  - Heroin use is postulated to act as a cofactor in the neuropathogenesis of human
      immunodeficiency virus (HIV-1) infection. Astrocytes, integral components of the
      CNS, are reported to be susceptible to HIV-1 infection. Upon activation,
      astrocytes release a number of immunoregulatory products or modulate the
      expression of a number of proteins that foster the immunopathogenesis of HIV-1
      infection. However, the role of heroin on HIV-1 infectivity and the expression of
      the proteome of normal human astrocytes (NHA) have not been elucidated. We
      hypothesize that heroin modulates the expression of a number of proteins by NHA
      that foster the neuoropathogenesis of HIV-1 infection. We utilized LTR
      amplification and the p24 antigen assay to quantitate the effect of heroin on HIV
      1 infectivity while difference gel electrophoresis (DIGE) combined with protein
      identification through high performance liquid chromatography-tandem mass
      spectrometry (HPLC-MS/MS) to analyze the effects of heroin on the proteomic
      profile of NHA. Results demonstrate that heroin potentiates HIV-1 replication in
      NHA. Furthermore, heroin significantly increased protein expression levels for
      protein kinase C (PKC), reticulocalbin 1 precursor, reticulocalbin 1, tyrosine 3
      monooxgenase/tryptophan 5-monooxgenase activation protein, chloride intracellular
      channel 1, cathepsin D preproprotein, galectin 1 and myosin light chain alkali.
      Heroin also significantly decreased protein expression for proliferating cell
      nuclear antigen, proteasome beta 6 subunit, tropomyosin 3, laminin receptor 1,
      tubulin alpha 6, vimentin, EF hand domain family member D2, Tumor protein D54
      (hD54), ATP synthase, H+ transporting, mitochondrial F1 complex and ribosomal
      protein S14. Identification of unique, heroin-induced proteins may help to
      develop novel markers for diagnostic, preventative and therapeutic targeting in
      heroin using subjects.

PMID- 17235378
TI  - Binding energies of the proton-bound amino Acid dimers gly.gly, ala.ala, gly.ala,
      and lys.lys measured by blackbody infrared radiative dissociation.
AB  - Arrhenius activation energies in the zero-pressure limit for dissociation of gas
      phase proton-bound homodimers of N,N-dimethylacetamide (N,N-DMA), glycine,
      alanine, and lysine and the heterodimer alanine.glycine were measured using
      blackbody infrared radiative dissociation (BIRD). In combination with master
      equation modeling of the kinetic data, binding energies of these dimers were
      determined. A value of 1.25 +/- 0.05 eV is obtained for N,N-DMA and is in
      excellent agreement with that reported in the literature. The value obtained from
      the truncated Boltzmann model is significantly higher, indicating that the
      assumptions of this model do not apply to these ions. This is due to the
      competitive rates of photon emission and dissociation for these relatively large
      ions. The binding energies of the amino acid dimers are ~1.15 +/- 0.05 eV and are
      indistinguishable despite the difference in their gas-phase basicity and
      structure. The threshold dissociation energies can be accurately modeled using a
      range of dissociation parameters and absorption/emission rates. However, the
      absolute values of the dissociation rates depend more strongly on the
      absorption/emission rates. For N,N-DMA and glycine, an accurate fit was obtained
      using frequencies and transition dipole moments calculated at the ab initio RHF/2
      31G* and MP2/2-31G* level, respectively. In order to obtain a similar accuracy
      using values obtained from AM1 semiempirical calculations, it was necessary to
      multiply the transition dipole moments by a factor of 3. These results
      demonstrate that in combination with master equation modeling, BIRD can be used
      to obtain accurate threshold dissociation energies of relatively small ions of
      biological interest.

PMID- 17235379
TI  - Human metapneumovirus in turkey poults.
AB  - This study was conducted to reexamine the hypothesis that human metapneumovirus
      (hMPV) will not infect turkeys. Six groups of 2-week-old turkeys (20 per group)
      were inoculated oculonasally with 1 of the following: noninfected cell
      suspension; hMPV genotype A1, A2, B1, or B2; or avian metapneumovirus (aMPV)
      subtype C. Poults inoculated with hMPV showed nasal discharge days 4-9
      postexposure. Specific viral RNA and antigen were detected by reverse
      transcription PCR and immunohistochemical evaluation, respectively, in nasal
      turbinates of birds exposed to hMPV. Nasal turbinates of hMPV-infected turkeys
      showed inflammatory changes and mucus accumulation. Each of the 4 hMPV genotypes
      caused a transient infection in turkeys as evidenced by clinical signs, detection
      of hMPV in turbinates, and histopathologic examination. Detailed investigation of
      cross-species pathogenicity of hMPV and aMPV and its importance for human and
      animal health is needed.

PMID- 17235380
TI  - Rho GTPase protein expression and activation in murine monocytes/macrophages is
      not modulated by model biomaterial surfaces in serum-containing in vitro
      cultures.
AB  - The Rho GTPase cellular signaling cascade was investigated in pro-monocyte and
      (monocyte-)macrophage cells by examining GTPase expression and activation in
      serum-containing cultures on model biomaterials. Abundance of Rho GDI and the Rho
      GTPase proteins RhoA, Cdc42 and Rac1 was determined in cells grown on tissue
      culture polystyrene, polystyrene, poly-l-lactide and Teflon((r)) AF surfaces.
      Protein expression was compared based on cell maturity (pro-monocyte to monocyte
      to macrophage lineages) and by model surface chemistry: Rho proteins were present
      in the majority of macrophage cells tested on model surfaces suggesting that a
      pool of Rho proteins is readily available for signaling events in response to
      numerous activating cues, including biomaterials surface encounter. Rho GTPase
      activation profiles in these cell lines indicate active Cdc42 and Rho proteins in
      RAW 264.7, Rac1 and Rho in J774A.1, and Cdc42 and Rac1 in IC-21 cell lines,
      respectively. Collectively, these proteins are known to play critical roles in
      all actin-based cytoskeletal rearrangement necessary for cell adhesion, spreading
      and motility, and remain important to establishing cellular responses required
      for foreign body reactions in vivo. Differences in Rho GTPase protein expression
      levels based on cell sourcing (primary versus secondary-derived cell source), or
      as a function of surface chemistry were insignificant. Rho GTPase expression
      profiles varied between pro-monocytic non-adherent precursor cells and mature
      adherent monocyte/macrophage cells. The active GTP-bound forms of the Rho GTPase
      proteins were detected from monocyte-macrophage cell lines RAW 264.7 and J774A.1
      on all polymer surfaces, suggesting that while these proteins are central to cell
      adhesive behavior, differences in surface chemistry are insufficient to
      differentially regulate GTPase activation in these cell types. Active Cdc42 was
      detected from cells cultured on the more-polar tissue culture polystyrene and
      poly-l-lactide surfaces after several days, but absent from those grown on apolar
      polystyrene and Teflon((r)) AF, indicating some surface influence on this GTPase
      in serum-containing cultures.

PMID- 17235381
TI  - Adding memantine to rivastigmine therapy in patients with mild-to-moderate
      alzheimer's disease: results of a 12-week, open-label pilot study.
AB  - OBJECTIVE: At present, inhibition of cholines-terase is the treatment of choice
      for subjects with mild-to-moderate Alzheimer's disease (AD). Memantine, a
      noncompetitive antagonist at N-methyl-d-aspartate receptors, is currently used to
      treat subjects with moderate-to-severe AD. The goal of this multicenter, open
      label pilot study was to investigate whether combination therapy with memantine
      added to rivastigmine is safe and beneficial in subjects with mild-to-moderate
      AD. METHOD: Patients with a DSM-IV diagnosis of dementia of the Alzheimer's type
      (N = 95), who were treated with rivastigmine (6-12 mg/day) for a maximum duration
      of 24 weeks prior to baseline, received memantine (5-20 mg/day) in combination
      with rivastigmine for 12 weeks. The primary efficacy variable was the change in
      the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) total
      score at the end of 12 weeks compared with baseline. The study was conducted
      between September 15, 2003, and May 27, 2004. RESULTS: There was a statistically
      significant difference between baseline and week 12 for the ADAS-cog total score,
      showing a positive effect of combination therapy. Combination therapy did not
      evidence any unexpected safety concerns and was well-tolerated by most patients.
      CONCLUSION: Memantine in combination with rivastigmine appears to be safe and
      beneficial in patients with mild-to-moderate AD. Our results need to be confirmed
      in a large, long-term, randomized, double-blind, placebo-controlled clinical
      trial.

PMID- 17235382
TI  - Factors associated with positive screens on the mood disorder questionnaire in
      primary care.
AB  - OBJECTIVE: This article examines the prevalence of positive testing for bipolar
      tendencies on the Mood Disorder Questionnaire (MDQ) in a primary care office
      setting. METHOD: Participants in this study were older than 18 years of age and
      had not been previously diagnosed with bipolar disorder at the time of study
      participation. 688 individuals submitted appropriately completed forms and were
      included in the study, which was conducted from October through November 2004.
      RESULTS: 10.8% of screened individuals tested positive for bipolar tendencies
      using the criteria determined by the investigators. These findings exceed
      estimates in previous studies of the prevalence of bipolar disorder in the
      general population. Statistically significant predictors of MDQ results included
      age (< 35 or >=?35 years), complaints of anxiety or depression, and psychotropic
      medication use (none, 1 or more). Study participants who were under 35 years of
      age and complained of anxiety or depression and took 1 or more psychotropic
      medications had a probability of testing positive on the MDQ of 0.45. Those under
      the age of 35 years who complained of anxiety or depression and had no history of
      psychotropic medication use had a probability of testing positive on the MDQ of
      0.27. The sample group consisting of individuals aged 35 years or older who
      complained of anxiety or depression and took psychotropic medications yielded a
      probability of positivity of 0.30; the probability of positivity for the 35-and
      over subgroup who complained of anxiety or depression but did not take
      psychotropic medications was 0.16. CONCLUSION: Participants who did not complain
      of anxiety or depression and did not have a history of psychotropic medication
      use exhibited a lower incidence of positive MDQ scores compared with those who
      did complain of anxiety and depression and did have a history of psychotropic
      medication use. No other correlations were found to be statistically significant.
      No separate validation of the MDQ results cited was independently performed
      during this study.

PMID- 17235384
TI  - Postdischarge treatment costs following closure of a state geropsychiatric ward:
      comparison of 2 levels of community care.
AB  - OBJECTIVES: The purposes of this study were to (1) examine the cost of community
      based health care services for geropsychiatric inpatients discharged into the
      community after the closure of an inpatient state geropsychiatric unit and (2)
      compare costs for patients treated with extra support through an Expanded
      Community Services (ECS) program to patients treated traditionally. METHOD: This
      study was a 6-month prospective, observational analysis of 30 patients discharged
      in conjunction with a ward closure in October 2002 (17 patients were nonrandomly
      assigned to the ECS program, and 13, to standard care). We analyzed costs of
      care, mortality, and rehospitalization rates derived from Medicaid paid claims
      and other data sources and compared costs to an estimate of hospital costs had
      the patients not been discharged. Patients were discharged to various community
      placements including long-term care facilities, assisted living facilities, and
      adult family homes in Eastern Washington State. RESULTS: Costs for community care
      were approximately half of estimated costs for hospital care. Patients treated in
      the ECS program, representing the most severely in-need discharges, had costs of
      care that were nonsignificantly higher than non-ECS patients but still
      significantly lower than estimated hospital care. No differences in mortality or
      rehospitalization rates were found between ECS and non-ECS patients. CONCLUSION:
      Costs of community care were significantly lower than hospital care. Quality of
      life for patients in the community settings versus the hospital was not assessed.
      The ECS program was able to maintain high-risk geropsychiatric patients in the
      community comparably to less severely ill patients at less than hospital costs.
      Recommendations are provided for ways to establish community treatment programs
      for deinstitutionalized elderly patients with serious mental illness.

PMID- 17235383
TI  - Effects of the antidepressant duloxetine on body weight: analyses of 10 clinical
      studies.
AB  - OBJECTIVE: To assess the effect of duloxetine, an inhibitor of serotonin and
      norepinephrine reup-take, on body weight of patients with major depressive
      disorder (MDD). METHOD: Body weight data were obtained from all 10 phase II and
      III registration studies of duloxetine in the treatment of MDD, as defined by the
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV),
      performed by Eli Lilly and Company between February 1999 and July 2003. Both
      acute (8-9 weeks) and long-term (26, 34, and 52 weeks) studies were analyzed.
      RESULTS: In the acute placebo-controlled studies, duloxetine-treated patients had
      a mean change of -0.5 kg compared with a change of 0.2 kg for placebo-treated
      patients (p < .001); no consistent relationship between duloxetine dose and
      weight change was observed. In placebo-controlled studies including an active
      comparator arm, similar acute mean weight changes were seen in duloxetine-treated
      and fluoxetine-treated patients (-0.7 kg vs. -0.6 kg) and in duloxetine-treated
      and paroxetine-treated patients (-0.3 kg vs. -0.2 kg). During longer-term
      treatment (34 weeks), mean weight change in patients treated with duloxetine 40
      mg b.i.d. was not significantly different from that seen in placebo-treated
      patients (0.7 kg vs. 0.1 kg), while patients treated with the higher duloxetine
      dose of 60 mg b.i.d. or with paroxetine gained significantly (p <=?.05) more
      weight than placebo-treated patients (0.9 kg, 1.0 kg, and 0.1 kg, respectively).
      In a 52-week open-label study, duloxetine-treated patients had a mean weight gain
      of 1.1 kg at endpoint (p < .001). CONCLUSION: Duloxetine-treated patients
      experienced weight loss after short-term treatment, followed by modest weight
      gain on longer-term treatment. The size of the weight changes observed suggests
      that the antidepressant duloxetine has minimal effects on weight for the majority
      of patients.

PMID- 17235385
TI  - Improving adherence to sertraline treatment: the effectiveness of a patient
      education intervention.
AB  - BACKGROUND: Previous attempts to improve anti-depressant adherence have achieved
      mixed results. The current study evaluated the effectiveness of a patient
      education intervention designed to increase adherence to sertraline treatment.
      METHOD: Data from a national pharmacy claims database were used to
      retrospectively match (along key demographic and clinical variables) consecutive
      patients prescribed sertraline (N = 1462) who received an educational
      intervention (Knowing More) between May 1, 2003, and April 30, 2004, with a
      control group of concurrent sertraline-treated patients who did not receive the
      intervention (N = 1462). The intervention consisted of 10 newsletters distributed
      over a 9-month period by mail and e-mail. The intervention and control groups
      were compared over a 7-month follow-up period on 3 adherence measures: time to
      discontinuation, days on therapy, and percentage of days on therapy. RESULTS: Cox
      regression analysis revealed that the time to discontinuation of sertraline
      (median = 100 days) was significantly greater (p < .0001) for the intervention
      group compared with the control group (median = 60 days). By the end of the
      follow-up period, 27% of patients remained on therapy with Knowing More versus
      15% of those not enrolled in the compliance program. The mean number of days on
      therapy was 24.8 days (25.5%) longer for the intervention group compared with the
      control group (122.5 days for the intervention group versus 97.7 days for the
      control group). The percentage of days on therapy was 88.2% for the intervention
      group versus 77.7% for the control group among patients with at least 1 refill
      prescription (p < .001). CONCLUSION: The educational compliance intervention,
      Knowing More, was associated with a significant increase in adherence to
      antidepressant treatment.

PMID- 17235387
TI  - The desire for death in the setting of terminal illness: a case discussion.

PMID- 17235386
TI  - Use of treatment algorithms for depression.
AB  - Depression continues to be a treatment challenge for many physicians
      psychiatrists and primary care physicians alike-in part because of the nature of
      the disorder, but also because of the wide variety of medications and other
      treatments available, each with a distinct efficacy and safety profile. One way
      of negotiating treatment decisions is to use treatment guidelines and algorithms.
      This Commentary, which appears in the September 2006 issue of The Journal of
      Clinical Psychiatry (2006;67:1458-1465), provides the primary care clinician with
      insight into the pros and cons of using treatment algorithms to guide the
      treatment of depression. -Larry Culpepper, M.D.

PMID- 17235388
TI  - Unconventional psychotherapy.

PMID- 17235389
TI  - "Let's cut to the chase-i need a pill".

PMID- 17235390
TI  - Careful monitoring for agranulocytosis during carbamazepine treatment.

PMID- 17235392
TI  - About the association of medicine and psychiatry.

PMID- 17235391
TI  - Crohn's disease mimicking bulimia nervosa.

PMID- 17235393
TI  - The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T-mediated
      virulence.
AB  - Pseudomonas aeruginosa, an important cause of opportunistic infections in humans,
      delivers bacterial cytotoxins by type III secretion directly into the host cell
      cytoplasm, resulting in disruption of host cell signaling and host innate
      immunity. However, little is known about the fate of the toxins themselves
      following injection into the host cytosol. Here, we show by both in vitro and in
      vivo studies that the host ubiquitin ligase Cbl-b interacts with the type III
      secreted effector exotoxin T (ExoT) and plays a key role in vivo in limiting
      bacterial dissemination mediated by ExoT. We demonstrate that, following
      polyubiquitination, ExoT undergoes regulated proteasomal degradation in the host
      cell cytosol. ExoT interacts with the E3 ubiquitin ligase Cbl-b and Crk, the
      substrate for the ExoT ADP ribosyltransferase (ADPRT) domain. The efficiency of
      degradation is dependent upon the activity of the ADPRT domain. In mouse models
      of acute pneumonia and systemic infection, Cbl-b is specifically required to
      limit the dissemination of ExoT-producing bacteria whereas c-Cbl plays no
      detectable role. To the best of our knowledge, this represents the first
      identification of a mammalian gene product that is specifically required for in
      vivo resistance to disease mediated by a type III-secreted effector.

PMID- 17235394
TI  - Direct interaction with filamins modulates the stability and plasma membrane
      expression of CFTR.
AB  - The role of the cystic fibrosis transmembrane conductance regulator (CFTR) as a
      cAMP-dependent chloride channel on the apical membrane of epithelia is well
      established. However, the processes by which CFTR is regulated on the cell
      surface are not clear. Here we report the identification of a protein-protein
      interaction between CFTR and the cytoskeletal filamin proteins. Using proteomic
      approaches, we identified filamins as proteins that associate with the extreme
      CFTR N terminus. Furthermore, we identified a disease-causing missense mutation
      in CFTR, serine 13 to phenylalanine (S13F), which disrupted this interaction. In
      cells, filamins tethered plasma membrane CFTR to the underlying actin network.
      This interaction stabilized CFTR at the cell surface and regulated the plasma
      membrane dynamics and confinement of the channel. In the absence of filamin
      binding, CFTR was internalized from the cell surface, where it prematurely
      accumulated in lysosomes and was ultimately degraded. Our data demonstrate what
      we believe to be a previously unrecognized role for the CFTR N terminus in the
      regulation of the plasma membrane stability and metabolic stability of CFTR. In
      addition, we elucidate the molecular defect associated with the S13F mutation.

PMID- 17235395
TI  - Digenic mutations account for variable phenotypes in idiopathic hypogonadotropic
      hypogonadism.
AB  - Idiopathic hypogonadotropic hypogonadism (IHH) due to defects of gonadotropin
      releasing hormone (GnRH) secretion and/or action is a developmental disorder of
      sexual maturation. To date, several single-gene defects have been implicated in
      the pathogenesis of IHH. However, significant inter- and intrafamilial
      variability and apparent incomplete penetrance in familial cases of IHH are
      difficult to reconcile with the model of a single-gene defect. We therefore
      hypothesized that mutations at different IHH loci interact in some families to
      modify their phenotypes. To address this issue, we studied 2 families, one with
      Kallmann syndrome (IHH and anosmia) and another with normosmic IHH, in which a
      single-gene defect had been identified: a heterozygous FGF receptor 1 (FGFR1)
      mutation in pedigree 1 and a compound heterozygous gonadotropin-releasing hormone
      receptor (GNRHR) mutation in pedigree 2, both of which varied markedly in
      expressivity within and across families. Further candidate gene screening
      revealed a second heterozygous deletion in the nasal embryonic LHRH factor (NELF)
      gene in pedigree 1 and an additional heterozygous FGFR1 mutation in pedigree 2
      that accounted for the considerable phenotypic variability. Therefore, 2
      different gene defects can synergize to produce a more severe phenotype in IHH
      families than either alone. This genetic model could account for some phenotypic
      heterogeneity seen in GnRH deficiency.

PMID- 17235398
TI  - [Do we have adequate antimicrobials against methicillin-resistant Staphylococcus
      aureus?].

PMID- 17235396
TI  - Neuronal SH2B1 is essential for controlling energy and glucose homeostasis.
AB  - SH2B1 (previously named SH2-B), a cytoplasmic adaptor protein, binds via its Src
      homology 2 (SH2) domain to a variety of protein tyrosine kinases, including JAK2
      and the insulin receptor. SH2B1-deficient mice are obese and diabetic. Here we
      demonstrated that multiple isoforms of SH2B1 (alpha, beta, gamma, and/or delta)
      were expressed in numerous tissues, including the brain, hypothalamus, liver,
      muscle, adipose tissue, heart, and pancreas. Rat SH2B1beta was specifically
      expressed in neural tissue in SH2B1-transgenic (SH2B1(Tg)) mice. SH2B1(Tg) mice
      were crossed with SH2B1-knockout (SH2B1(KO)) mice to generate SH2B1(TgKO) mice
      expressing SH2B1 only in neural tissue but not in other tissues. Systemic
      deletion of the SH2B1 gene resulted in metabolic disorders in SH2B1(KO) mice,
      including hyperlipidemia, leptin resistance, hyperphagia, obesity, hyperglycemia,
      insulin resistance, and glucose intolerance. Neuron-specific restoration of
      SH2B1beta not only corrected the metabolic disorders in SH2B1(TgKO) mice, but
      also improved JAK2-mediated leptin signaling and leptin regulation of orexigenic
      neuropeptide expression in the hypothalamus. Moreover, neuron-specific
      overexpression of SH2B1 dose-dependently protected against high-fat diet-induced
      leptin resistance and obesity. These observations suggest that neuronal SH2B1
      regulates energy balance, body weight, peripheral insulin sensitivity, and
      glucose homeostasis at least in part by enhancing hypothalamic leptin
      sensitivity.

PMID- 17235399
TI  - [Peramivir. A new and potent neuraminidase inhibitor for the treatment of
      influenza].

PMID- 17235397
TI  - Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of
      lymphoma.
AB  - Autophagy is a lysosome-dependent degradative pathway frequently activated in
      tumor cells treated with chemotherapy or radiation. Whether autophagy observed in
      treated cancer cells represents a mechanism that allows tumor cells to survive
      therapy or a mechanism for initiating a nonapoptotic form of programmed cell
      death remains controversial. To address this issue, the role of autophagy in a
      Myc-induced model of lymphoma generated from cells derived from
      p53ER(TAM)/p53ER(TAM) mice (with ER denoting estrogen receptor) was examined.
      Such tumors are resistant to apoptosis due to a lack of nuclear p53. Systemic
      administration of tamoxifen led to p53 activation and tumor regression followed
      by tumor recurrence. Activation of p53 was associated with the rapid appearance
      of apoptotic cells and the induction of autophagy in surviving cells. Inhibition
      of autophagy with either chloroquine or ATG5 short hairpin RNA (shRNA) enhanced
      the ability of either p53 activation or alkylating drug therapy to induce tumor
      cell death. These studies provide evidence that autophagy serves as a survival
      pathway in tumor cells treated with apoptosis activators and a rationale for the
      use of autophagy inhibitors such as chloroquine in combination with therapies
      designed to induce apoptosis in human cancers.

PMID- 17235400
TI  - [Antimicrobial prophylaxis for surgery].

PMID- 17235401
TI  - [Influence of the displacement of protein binding by ibuprofen in the activity of
      a third-generation cephalosporin against Streptococcus pneumoniae].
AB  - The clinical significance of protein binding remains to be fully elucidated. The
      aim of this study was to evaluate the effect in the in vitro bactericidal
      activity of cefditoren through killing curves at Cmax concentrations against
      three Streptococcus pneumoniae strains (cefditoren MICs of 0.12, 0.25 and 0.5
      mg/l) with or without human albumin (4 g/dl) and ibuprofen at Cmax concentrations
      (32.3 mg/l) and 10 times the Cmax (323 mg/l). Cefditoren was rapidly bactericidal
      (3 log(10) CFU/ml reduction) against the three strains at 4.2 mg/l concentration
      in Mueller-Hinton broth plus 5% lysed horse blood. In presence of human albumin,
      this effect was maintained against the most susceptible strain (MIC = 0.12 mg/l).
      Regrowths were observed with higher MIC values. The presence of ibuprofen (32.3
      mg/l) slightly delayed regrowth while the increase of ibuprofen concentration up
      to 10 x Cmax recovered the bactericidal activity against all strains. The
      activity of an antimicrobial with high protein binding should not be linked
      exclusively with the theoretical unbound fraction extrapolated from the plasma
      concentration. The role of protein binding antagonists merits analysis due to
      their frequent use associated with cephalosporins in respiratory tract
      infections.

PMID- 17235402
TI  - [Acute mastoiditis: increase of incidence and controversies in antibiotic
      treatment].
AB  - An important complication of acute otitis media is acute mastoiditis which
      responds to antibiotic therapy and myringotomy. Patients with acute mastoiditis
      were reviewed during 1996-2005 in the tertiary University Children's Hospital in
      Madrid. The number of patients with acute mastoiditis increased by about 2-fold
      during this period. Of 205 children with mastoiditis, ranging from 0.6-17 years
      of age, surgical treatment was needed in about 4.3% in 1996 and in 70% in 2005.
      In spite of 80% of the children having received antibiotics at the pediatric
      visit, the number of complications increased (periostitis, subperiosteal
      abscess), and the number of surgical interventions increased by 8-fold.
      Etiological agents were Streptococcus pneumoniae (28.5%) and Staphylococcus
      aureus (16.3%). Negative cultures were obtained in 53.6% of cases. Lack of
      response to conventional therapy may require more tympanocentesis procedures for
      a middle ear culture, and surgical therapy may be necessary more often, as is the
      tendency in our hospital.

PMID- 17235403
TI  - [Geographic variability in prescribing antibiotics in the pediatric population of
      Castille and Leon during 2001-2005].
AB  - The aim of this study was to determine if there were differences in the
      antibiotic consumption among the pediatric population of the eleven Primary
      Health Care centers in the Community of Castilla Leon during the years 2001-2005
      and to analyze the possible causes. Data of non-hospital antibiotic consumption
      in the pediatric population provided the amount of antibiotics billed in the
      Health Service of the area of Castilla and Leon (central region of Spain). The
      data was analyzed according to the Anatomic Therapeutic Chemical Classification
      System (ATC) and expressed as defined daily doses per 1000 inhabitants per day
      (DID). There were statistically significant differences in the use of
      antibiotics, varying 8.3 DID between the area with the highest rate (24.86 DID in
      Leon) and the area with the lowest rate (16.56 DID in Soria). The temporal
      fluctuations were great and varied especially in Segovia. The pattern of
      prescribing also varied. The use of penicillin in combination with beta
      lacatamase inhibitors varied by a factor of almost three times between Burgos and
      Segovia. Segovia showed the best management in antibiotic prescriptions with data
      showing low consumption based on prescribing recommendations. Data from Soria
      showed low consumption but patterns of misuse in regard to protocols and
      prescribing. There was wide quantitative and qualitative variability of
      antibiotic use among the primary health care centers in the region of Castilla
      and Leon. More detailed studies by age groups, welfare pressure and indication
      are needed to better understand the determinants of antibiotic use in children.

PMID- 17235404
TI  - [National multicenter survey: the use of intravenous antimicrobial agents].
AB  - Infectious diseases are currently one of the major health problems worldwide. As
      a consequence, both nosocomial and community-acquired infections are responsible
      for a significant increase in workload and health costs for hospitals,
      particularly in Intensive Care Units (ICU), Internal Medicine and Surgery. The
      use of intravenous antimicrobial agents is common in hospitalized patients. In
      order to determine the use of antimicrobial agents and the most frequent
      procedures used for their administration in Spanish hospitals, a national
      multicenter survey was undertaken among ICU, Internal Medicine and Surgery health
      staff from 63 hospitals, in which data were collected on central and peripheral
      catheter manipulation and intravenous administration. Results showed that, in
      Spain, both catheter manipulation (insertion, maintenance and removal) and
      administration of antimicrobial agents are performed by the nursing staff
      following established protocols, particularly for central catheters. Moreover,
      the ICUs had the highest rates of catheter-bearing patients, as well as patients
      undergoing antimicrobial treatment, sometimes in combination. The use of
      intravenous antimicrobial agents in Spanish hospitals results in an increased
      workload for the nursing staff and higher health costs, not to mention the risk
      involved with the use of vascular catheters.

PMID- 17235405
TI  - [Bacteroides fragilis group in non-diarrheal human feces and its antimicrobial
      susceptibility].
AB  - Bacteroides is a predominant anaerobic bacteria of the human colon. Since the ten
      species of the Bacteroides fragilis group are responsible for most anaerobic
      endogenous infections, the antimicrobial resistance of these bacteria is of great
      concern due to the role they can play in the dissemination of resistance. Eighty
      non-diarrheic human feces samples were analyzed. Each sample was inoculated in
      BBE (Bacteroides Bile Esculin) and KVLB (Kanamycin, Vancomycin, Laked Blood) agar
      plates and were incubated in anaerobic conditions for 48 h at 35 degrees C. For
      identification and antimicrobial sensitivity, miniaturized systems for anaerobic
      bacteria (Rapid ID-32A and ATB ANA, Biomerieux) were used. Sixty-four (80%) of
      the samples were positive for at least one Bacteroides fragilis species; B.
      uniformis and B. fragilis were the most frequent species (24.6% and 16.9%); B.
      stercoris and B. eggerthii were the least frequent (0.7 and 2.1%). The strains
      showed resistance to different penicillins (40.2-93.1%), some even in the
      presence of beta-lactamase inhibitors, to cephalosporins (31.0-52.1%) and to
      frequently used antibiotics against anaerobes, such as clindamycin (32.2%) and
      imipenem (10.3%). The most effective antimicrobials against Bacteroides fragilis
      were piperacillin and ticarcillin combined with beta-lactamase inhibitors, as
      well as chloramphenicol and metronidazole (>90% susceptibility). None of the B.
      fragilis group were resistant to clindamycin or metronidazole, but one-third of
      the imipenem-resistant strains belonged to this species. The most resistant
      species was B. distasonis, while B. vulgatus was the most susceptible. None of
      the tested antimicrobials were effective against all ten species; the majority of
      the species had some isolates that were resistant to imipenem, metronidazole or
      clindamycin. This resistance pattern suggests the presence of efficient
      transmission mechanisms among these endogenous bacteria.

PMID- 17235406
TI  - [Decrease in bactericidal activity of ciprofloxacin in Salmonella mutants
      generated following repeated exposure to various fluorquinolones].
AB  - Salmonella mutants with reduced fluoroquinolone susceptibility were generated in
      vitro following repeated exposure to subinhibitory concentrations of the drugs
      and the alterations in the gyrA gene were characterized. Afterwards, the change
      in bactericidal activity exhibited by ciprofloxacin against the resulting mutants
      was determined. A decrease in the bactericidal activity of ciprofloxacin was
      found in all the mutants, but was more pronounced in mutants of nalidixic acid
      resistant strains. This may help to explain the therapeutic failures sometimes
      described when fluoroquinolones are used in the treatment of these strains. In
      addition, our model evaluates the first interactions produced between the
      microorganism and the antibiotics, and demonstrates that the loss of bactericidal
      activity of ciprofloxacin occurs following exposure to all of the
      fluoroquinolones tested.

PMID- 17235407
TI  - Group A streptococcal bacteremia: outcome and prognostic factors.
AB  - In the last two decades, an increase in the incidence of invasive group A
      streptococcus (GAS) infections has been reported. The aim of this study was to
      determine the clinical and epidemiological characteristics and the natural
      history of GAS bacteremias at our hospital by performing a retrospective study of
      all cases of GAS bacteremia diagnosed at our University hospital from 1994 to
      2003. We reported 42 cases of GAS bacteremia (27 men, mean age 42.3 +/- 31.6
      years). None had more than one episode and four cases were nosocomial. The mean
      annual incidence rate was 1.01 cases per 100,000 population. An increase in the
      incidence but not in severity of GAS bacteremia was observed in the last 5-year
      period (p<0.001). The rates were highest in young children and the elderly and
      those with underlying medical conditions; 73.8% of patients had some underlying
      chronic illness, and the most relevant conditions included peripheral vascular
      disease and diabetes mellitus. Mortality was high and the worst outcome
      corresponded to elderly patients with streptococcal toxic shock syndrome (STSS).
      Thirty patients (71.4%) had a disruption in the integrity of the skin barrier, 14
      (33.3%) were immunocompromised patients and 6 patients (14.3%) were intravenous
      drug users. A source of the bacteremia was noted in 38 patients (90.5%), with
      skin and soft tissue infection being the major portals of entry. Twelve patients
      (28.6%) fulfilled the STSS criteria. All strains were susceptible to penicillin
      and vancomycin. Resistance to erythromycin was 21.4% and to ciprofloxacin was
      17.5%. The global mortality rate was 28.6%. Only STSS was significantly
      associated with increased mortality in the multivariate analysis.

PMID- 17235408
TI  - [Musculoskeletal adverse effects of levofloxacin].

PMID- 17235410
TI  - [October 30, 1928, a key date in Fleming's diary].

PMID- 17235409
TI  - [Treatment guide for skin and soft tissue infections. Spanish Chemotherapy
      Society, Spanish Internal Medicine Society, Spanish Association of Surgeons].

PMID- 17235411
TI  - Antibacterial agents in the cinema.
AB  - Numerous procedures used as antibacterial therapy are present in many films and
      include strategies ranging from different antimicrobial drugs to surgery and
      supporting measures. Films also explore the correct use and misuse of
      antimicrobial agents. Side effects and other aspects related to antibacterial
      therapy have also been reflected in some films. This article refers to the
      presence of antibacterial agents in different popular movies. There are movies in
      which antibacterial agents form part of the central plot, while in others it is
      merely an important part of the plot. In still others, its presence is isolated,
      and in these it plays an ambient or anecdotal role.

PMID- 17235412
TI  - Possible role of poly(ADP-ribose) polymerase in pathological and physiological
      cardiac hypertrophy.
AB  - The present study was designed to investigate the effect of 5-aminoisoquinoline,
      a specific poly(ADP-ribose) polymerase (PARP) inhibitor, in partial abdominal
      aortic constriction (PAAC) for 4 weeks it induced pathological and chronic
      swimming training (CST) for 8 weeks it induced physiological cardiac hypertrophy.
      5-Aminoisoquinoline (0.3 mg/kg/day and 3 mg/kg/day, i.p.) treatment was started 3
      days before PAAC and CST, and it was continued for 4 weeks after PAAC and 8 weeks
      after initiation of CST. The left ventricular (LV) function and LV hypertrophy
      were assessed by measuring LVDP, dp/dtmax, dp/dtmin, ratio of LV weight to body
      weight (LVW/BW), LV wall thickness (LVWT), LV collagen content, LV protein
      content, and LV RNA concentration. Further, venous pressure (VP) and mean
      arterial blood pressure (MABP) were recorded. The PAAC, but not CST, produced LV
      dysfunction by decreasing LVDP, dp/dtmax, dp/dtmin, and increasing LV collagen
      content. Further, PAAC and CST were noted to produce LV hypertrophy by increasing
      LVW/BW, LVWT, LV protein content, and LV RNA concentration. Moreover, in contrast
      to CST, PAAC significantly increased VP and MABP. The 5-aminoisoquinoline, a
      potent selective inhibitor of PARP, significantly attenuated PAAC-induced LV
      dysfunction, LV hypertrophy, increase in VP and MABP. On the other hand,
      treatment with 5-aminoisoquinoline did not modulate CST-induced physiological
      cardiac hypertrophy. These results implicate PARP in PAAC-induced LV dysfunction
      and pathological cardiac hypertrophy. However, PARP may not be involved in CST
      induced physiological cardiac hypertrophy.

PMID- 17235413
TI  - Effect of pioglitazone on the expression of inflammatory cytokines in attenuating
      rat cardiomyocyte hypertrophy.
AB  - Pioglitazone, one of the synthetic peroxisome proliferator-activated receptor
      (PPARgamma) agonists, has been found to inhibit inflammatory response. However,
      it is not known yet whether the preventive effect of pioglitazone on cardiac
      hypertrophy is related to its antiinflammatory function. The objective of this
      study was to investigate the role of pioglitazone in attenuation of cardiac
      hypertrophy and its relation to the inhibitory effect on the inflammatory
      cytokine expression in cultured neonatal rat cardiomyocytes. The mRNA expression
      of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), interleukin
      (IL)-1beta, IL-6, and PPARgamma was measured by using RT-PCR. Cardiomyocyte
      hypertrophy was induced by stimulating angiotensin II (Ang II) and evaluated both
      by measuring surface area of cardiac myocyte and 3H-leucine incorporation. The
      expressions of IL-1beta, IL-6, ANP, and BNP were significantly enhanced, whereas
      that of PPARgamma was significantly reduced in Ang II-induced hypertrophic
      cardiomyocytes. Pioglitazone decreased cardiac myocyte surface area and inhibited
      3H-leucine incorporation into cardiomyocytes. Furthermore, pioglitazone
      upregulated the suppressed expression of PPARgamma and attenuated the increased
      IL-1beta and IL-6 expression. The effect of pioglitazone might be associated with
      PPARgamma activation and the consequent antiinflammatory function in prevention
      and treatment of cardiac hypertrophy.

PMID- 17235414
TI  - Esmolol inhibits Na+ current in rat ventricular myocytes.
AB  - Esmolol is a unique cardioselective, intravenous, ultra-short acting, beta1
      adrenergic blocking agent. It has been widely applied in treating ventricular and
      supraventricular arrhythmias, especially in emergency situations. In this study
      the effects of esmolol on sodium current (I(Na)) were investigated by the whole
      cell patch-clamp recording technique in isolated adult rat ventricular myocytes.
      The results indicated that esmolol reversibly inhibited I(Na) in a concentration
      dependent manner, with an IC50 of 74.2 +/- 0.60 micromol l(-1) with a Hill
      coefficient of 1.02 +/- 0.04. This inhibition was voltage- and frequency
      dependent. Esmolol decreased the peak of the I-V relationship curve at -35 mV
      from 16.97 +/- 1.68 pA/pF to 6.96 +/- 0.51 pA/pF. The steady-state inactivation
      curve of I(Na) was shifted to more negative potentials, the voltage at half
      inactivation changing from -78.75 +/- 2.3 mV in control to -85.94 +/- 3.2 mV in
      the presence of esmolol. The development of resting inactivation from closed
      states was accelerated by esmolol, the time constant was shortened from 62.75 +/-
      3.21 ms to 24.93 +/- 2.43 ms, whereas the activation curve was not altered. I(Na)
      from inactivation could not be recovered completely in the presence of esmolol.
      These results suggest that esmolol inhibits I(Na) through sodium channel in rat
      ventricular myocytes by mechanisms involving preferential interaction with the
      inactivated state and acceleration of the development of inactivation directly
      from resting state. Therefore, the effect of inhibitory sodium of esmolol may
      play a vital role in its antiarrhythmic efficacy.

PMID- 17235415
TI  - What is the risk of pyelonephritis due to desmopressin in rats with cystitis?
AB  - The risk of pyelonephritis in children with asymptomatic cystitis or bacteriuria,
      using desmopressin for primary nonpoliuric nocturnal enuresis, is not known. The
      aim of this study was to study whether there is a risk of pyelonephritis in rats
      with cystitis using desmopressin. Wistar rats (n = 28) were divided into four
      groups of cystitis (groups I-IV). DDAVP (2 microg daily) and saline (0.5 ml
      daily) were injected intramuscularly for 7 days in groups II and IV and groups I
      and III, respectively. The urinalysis, urine culture, and 24-h urinary volume
      (UV(24)) were assessed for all rats on days 1, 3, 5, and 7. In groups III and IV
      these studies were also performed on days 14, 21, and 28. Serum creatinine was
      determined on day 7 in all rats and on day 28 in groups III and IV. Groups I and
      II and groups III and IV were killed at the end of days 7 and 28, respectively.
      Kidneys and urinary bladders were graded subjectively for inflammation and
      fibrosis. Inflammation and fibrosis scores in kidney and bladder tissues were not
      different between DDAVP or saline-injected rats in cystitis groups at weeks 1 and
      4. No fibrosis was found in any of the urinary bladders on histological
      examination. Ascendant pyelonephritis was detected in each of the four rats in
      DDAVP-administered and saline-administered cystitis groups. The histopathologic
      scores of the renal tissue with pyelonephritis showed no correlation with the
      daily urine volume, the positive test results for urine leukocyte esterase with
      dipstick test, the urine culture results for E. coli based on colony-forming unit
      per milliliter, or serum creatinine levels in cystitis groups. It was found that
      the administration of DDAVP to cystitis groups did not increase the risk of
      ascendant pyelonephritis.

PMID- 17235417
TI  - Subacute bloodstream blockade effect by supercontraction of spider silk.
AB  - The present experiment was designed to test the subacute bloodstream blockade
      effect of supercontraction of spider silk on the femoral artery of rats.
      Observation on ligated femoral artery lasted 10 days. Blood flow,
      systolic/diastolic blood pressure, and oxidatively modified proteins in serum
      were measured before and after ligation. Meanwhile, histological manifestations
      of femoral artery at different times were observed by HE stain. We found that
      blood flow and systolic/diastolic blood pressure of femoral artery showed a
      descending tendency. Biochemical assay showed that oxidatively modified proteins
      significantly increased in the first 3 days and reached peak on the third day.
      Histological examination demonstrated that there was a progressive procedure from
      partial to complete occlusion of lumen of blood vessel and there was possibility
      of recanalization at last in the occlusive vessel. Our study indicated that
      ligation by spider silk might be applied to models of subacute ischemic disease
      such as subacute femoral artery ischemia, subacute or chronic ischemic
      cardiocerebrovascular disease, etc.

PMID- 17235416
TI  - Topical capsaicin application and axon reflex vasodilatation of the tongue:
      neurogenic involvement in burning mouth syndrome.
AB  - The aim of this study was to evaluate the effects of topical capsaicin
      application on human lingual mucosa and to assess if neurogenic inflammation
      might have a role in the pathogenesis of lingual diseases. Thirty patients (16
      males and 14 females; mean age: 41.46 +/- 11.8 years; range: 23-60) were examined
      in our laboratory. The neurogenic inflammation was experimentally induced in the
      lingual mucosa close to 1) the left margin of the tongue and 2) the right margin
      of the tongue after ipsilateral nerve trunk anesthesia. The characteristics of
      lingual microcirculation were observed using computerized videocapillaroscopic
      techniques. The vasodilatation was observed close to the left margin of the
      tongue, and an important correlation was observed between capsaicin application
      and capillary tortuosity. No significant modifications in vascular diameter and
      tortuosity were observed after capsaicin application close to the right margin of
      the tongue. The results of the present study are of interest, in particular, in
      regard to recent studies pointing to neurogenic involvement in oral diseases such
      as burning mouth syndrome.

PMID- 17235418
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: 5-Methyltetrahydrofolate, 9
      aminocamptothecin; AdPEDF.11, AE-37, albumin interferon alfa, alicaforsen sodium,
      alvocidib hydrochloride, AMG-706, arginine butyrate, avanafil, axitinib,
      azimilide hydrochloride; BAY-579352, belagenpumatucel-L, beta-lapachone, BHT
      3009, BIBW-2992, bremelanotide, BX-471; Casopitant mesylate, cediranib,
      certolizumab pegol, CH-1504, ChimeriVax-West Nile, clofazimine, CpG-7909,
      curcumin, Cypher; Dapoxetine hydrochloride, darusentan, diflomotecan, D
      methionine, dnaJP1, D-serine, DTPw-HB Hib-MenAC, DTPw-HepB-Hib; E-7010,
      ecogramostim, edodekin alfa, EGFRvlll peptide vaccine, elcometrine,
      elcometrine/ethinylestradiol, elsilimomab, enrasentan, ertumaxomab, etalocib
      sodium, exisulind; Fenretinide, fesoterodine, fingolimod hydrochloride,
      fontolizumab; Gefitinib, gemtuzumab ozogamicin, ghrelin (human), GV-1001; HTU-PA,
      human papillomavirus vaccine; Indacaterol, indiplon, interleukin-21, intranasal
      insulin, irinotecan hydrochloride/floxuridine, ISIS-301012, ispinesib mesylate,
      ixabepilone; K562/GM-CSF; Lapatinib, L-BLP-25, linezolid, liposome encapsulated
      paclitaxel, LY-2124275; MC-1, MC-1/lisinopril, MDX-066, melanoma vaccine, MMR-V,
      multivalent (ACYW) meningitis vaccine; Nilotinib, nobori, nociceptin; Oblimersen
      sodium, orbofiban acetate, ospemifene; Paliperidone, panitumumab, PEG-filgrastim,
      PEGylated interferon alfacon-1, perflubutane, pertuzumab, phenserine tartrate,
      phVEGF-A165, pleconaril, prasugrel, prednisolone sodium metasulfobenzoate; R-411,
      recombinant malaria vaccine, rhGM-CSF, roflumilast, romidepsin, ruboxistaurin
      mesilate hydrate; Sirolimus-eluting stent, SR-4554, St. John's Wort extract;
      Talabostat, Taxus, TGN-255, tifacogin, tiotropium bromide, tolevamer sodium,
      trabectedin, tretinoin LF; Vatalanib succinate; Yellow fever vaccine, YM-155.

PMID- 17235420
TI  - Safety and efficacy of the AngioJet in patients with acute myocardial infarction:
      results from the Florence Appraisal Study of Rheolytic Thrombectomy (FAST).
AB  - OBJECTIVES: To assess the safety and efficacy of the AngioJet coronary device,
      given the uncertain risk-benefit balance of rheolytic thrombectomy in patients
      with acute myocardial infarction (AMI). BACKGROUND: Current risk of inadequate
      myocardial perfusion for thrombus embolization in primary coronary interventions
      is not negligible. The AngioJet thrombectomy device showed promising results in
      terms of safety and efficacy, but failed to confirm them in a large, multicenter,
      randomized trial, and the risk-benefit balance is still uncertain. METHODS: The
      AngioJet device was employed in 116 consecutive patients with AMI and
      angiographic evidence of extensive thrombosis in a vessel with a reference
      diameter > 2.5 mm. Stents and glycoprotein IIb/IIIa inhibitors were liberally
      used. Epicardial and myocardial reperfusion angiographic parameters, and in
      hospital major adverse cardiac events (MACE, i.e., cardiac death, myocardial
      infarction, target vessel revascularization) were assessed. RESULTS: The AngioJet
      was successfully used in all patients. Angiographic analysis showed that the
      AngioJet significantly improved epicardial coronary flow (p < 0.01), frame count
      (p < 0.01) and myocardial blush (p < 0.01), while stenting yielded significant
      improvements only in diameter stenosis, minimum lesion diameter and correlated
      vessel parameters (p < 0.01). In-hospital MACE were uncommon [9 (8%)], despite
      the patientsO characteristics. When compared to an AMI population with similar
      thrombus burden but not undergoing thrombectomy, our AngioJet population showed
      significant improvement of reperfusion parameters. Moreover, there was greater
      AngioJet benefit in the high versus moderate thrombus burden subset; laboratory
      and operator experience also correlated significantly with final angiographic
      results. CONCLUSIONS: Our study supports the favorable risk-benefit profile of
      AngioJet device use in selected patients with AMI when used in experienced
      laboratories and by trained operators.

PMID- 17235419
TI  - Direct versus predilatation drug-eluting stenting: a randomized clinical trial.
AB  - BACKGROUND: Direct stenting without balloon predilatation has been shown to be
      feasible and safe with drug-eluting stents, but no randomized comparisons between
      the two strategies exist. This study was designed to compare direct stenting with
      balloon predilatation followed by stent placement using only drug-eluting stents.
      METHODS: One hundred and sixty-six consecutive coronary lesions in 95 consenting
      patients (mean age 59 +/- 11 years; 12 women) were randomly assigned to direct
      stenting (n = 88), or balloon predilatation followed by stenting (n = 78), using
      sirolimus- or paclitaxel-eluting stents. RESULTS: All procedures were uneventful.
      Crossover to balloon predilatation was necessary in 6 (7%) lesions randomized to
      direct stenting. During a 12-month follow up period, ischemia-driven angiography
      was performed in 13 patients. By intention to treat analysis, target lesion
      revascularization was required in 4 lesions, all of which were randomized to the
      predilatation group (p = 0.04). CONCLUSIONS: Direct stenting was feasible in up
      to 93% of attempted lesions. A strategy of direct stenting resulted in a
      significantly lower rate of target lesion revascularization over a 12-month
      follow-up period compared to balloon predilatation followed by stenting.

PMID- 17235421
TI  - [Cerebellar syndromes in Langerhans' cell histiocytosis].
AB  - We report a 24-year-old patient with a progressive cerebellar syndrome and
      history of Langerhans' cell histiocytosis. Neurological symptoms started 5 years
      after completion of combined radio- and chemotherapy which had led to complete
      and permanent remission of the primary disease. The clinical and
      neuroradiological findings obtained mirror progressive neurodegenerative
      alterations of the cerebellum that represent one of the three classic CNS
      manifestations of Langerhans' cell histiocytosis.

PMID- 17235422
TI  - [Central core myopathy: a juvenile and adult disease].
AB  - Central core myopathy is a nonprogressive or only slowly progressive congenital
      muscle disease. In most cases, symptoms begin in childhood, but rare cases with
      adult onset are described. Regardless of its high variability, the clinical
      hallmarks are diffuse muscle weakness and the development of multiple bone
      deformities and contractures. Skeletal muscle biopsy is of high diagnostic
      significance. Due to a potential association with malignant hyperthermia, early
      diagnosis is of great importance. A curative treatment is not currently known.
      Here we discuss aetiology, pathogenesis, clinical features, diagnosis,
      differential diagnosis, therapeutic strategies, and prognosis of central core
      myopathy based on a clinical example with an atypical onset of symptoms in
      adulthood.

PMID- 17235423
TI  - [N-acetyl-L-cysteine as a therapeutic option in bacterial meningitis].
AB  - Despite antibiotic therapy, supportive intensive care, and adjunctive treatment
      with dexamethasone, the mortality and morbidity remain high in patients with
      bacterial meningitis. The intracranial complications that mainly contribute to
      the poor outcome are in part a result of the production of reactive oxygen and
      nitrogen species. Experimental studies have shown that the prognosis for
      bacterial meningitis can be improved by the administration of antioxidants.
      Especially adjunctive therapy with N-acetyl-L-cystein (NAC) was shown to have
      mainly positive effects. Since NAC is already in clinical use in high doses for
      treating other diseases (e.g., acetaminophen intoxication) and only minor side
      effects have been observed, there is justified hope that adjunctive therapy with
      NAC could improve the prognosis of patients with bacterial meningitis.

PMID- 17235425
TI  - [Communication from the DGPPN (German Society of Psychiatry, Psychotherapy and
      Neurology) 1/2007].

PMID- 17235427
TI  - Sleep disorders in Parkinson's disease: facts and new perspectives.
AB  - Awareness of the clinical and pathophysiological importance of sleep disorders in
      Parkinson's disease (PD) has been growing in recent years. Sleep disorders are
      now regarded as important among non-motor symptoms in PD and as a significant
      variable of PD-related quality of life. Furthermore, some sleep disorders, namely
      REM behaviour disorder (RBD), has been hypothesised to herald PD by years.
      Subjective reports of disrupted nocturnal sleep and daytime sleepiness appear to
      be supported by descriptions of several sleep alterations at nocturnal
      polysomnographic investigation and Multiple Sleep Latency Test findings. Sleep
      alterations in PD are to be viewed from the multifactorial perspective of a
      framework of reciprocally interacting factors: pathophysiology of the disease
      itself, sleep-related motor symptoms, dopaminergic treatments, ageing,
      depression, restless legs, periodic limb movements (PMLs) and sleep-disordered
      breathing. Ad hoc questionnaires and scales such as the Parkinson's Disease Sleep
      Scale and the Short and Practical (SCOPA) Sleep Scale are now available for the
      evaluation of disordered sleep in PD patients and have been proved to be useful
      for preliminary screening of sleep disorders in PD. However in a few cases a
      video-polysomnography (V-PSG) is needed in order to confirm a diagnosis of sleep
      disorder in PD, particularly in diagnosing RBD. As for treatment of sleep
      disorders, combined pharmacological and non-pharmacological protocols appear to
      be particularly suitable in their treatment in PD.

PMID- 17235424
TI  - [Treatment strategies for tetanus].
AB  - As a result of active immunisation, tetanus has become a rare but still severe
      neurological disease in the developed world. Despite modern intensive care
      management, mortality ranges between 20 and 50%. Introduction of mechanical
      ventilation dramatically reduced mortality; the life-threatening vegetative
      dysfunctions with cardiovascular instability are now the main reasons for the
      remaining poor prognosis. This report provides information about clinical
      features, diagnosis and prophylaxis of the disease and gives an overview of the
      therapeutic principles of generalized tetanus, focusing on the management of
      autonomic instability.

PMID- 17235428
TI  - Idiopathic rapid eye movement sleep behaviour disorder.
AB  - Rapid eye movement (REM) sleep behaviour disorder (RBD) is a parasomnia
      characterised by elaborate behaviours during REM sleep usually associated with
      action-filled dreams. Typical behaviours are screaming, grasping, punching,
      kicking and occasionally jumping out of bed, which are potentially harmful for
      the patient and their bed partner. Polysomnographic (PSG) recording reveals a
      loss of atonia and an excessive phasic motor activity during REM sleep. RBD
      affects mainly men over 50 years and its prevalence in the general population is
      estimated around 0.5%. It may occur in acute or chronic forms. The latter may be
      isolated (idiopathic RBD), or associated with other neurological diseases
      (symptomatic RBD), especially with a group of neurodegenerative disease called
      alpha-synucleinopathies, which includes Parkinson's disease, dementia with Lewy
      bodies (DLB) and multiple system atrophy. The idiopathic form accounts for up to
      60% of the cases reported in the literature. Small clinical follow-up studies
      revealed that a proportion of these patients will eventually develop a
      parkinsonian syndrome and/or a DLB in the years following the RBD diagnosis,
      while some patients will remain idiopathic for decades. Recent studies found
      evidence of neural dysfunction during both wakefulness and sleep in iRBD, such as
      an impairment of the cortical activity, specific neuropsychological deficits,
      signs of autonomic dysfunction, deficit of colour discrimination, subtle
      abnormalities in quantitative measures of motor and gait speed and an olfactory
      impairment. The notion of "idiopathic" RBD is currently challenged and the use of
      a more conservative term of "cryptogenic" RBD has been suggested.

PMID- 17235429
TI  - Symptomatic REM sleep behaviour disorder.
AB  - Rapid eye movement (REM) sleep behaviour disorder (RBD) precedes or accompanies
      many neurodegenerative disorders. In synucleinopathies, including dementia with
      Lewy bodies, Parkinson's disease and multiple system atrophy, the prevalence of
      RBD varies from 19% to almost 77% in different reports. In tauopathies, including
      Alzheimer's disease, corticobasal degeneration, progressive supranuclear palsy
      and frontotemporal dementia, the prevalence is rare, ranging from 0% to 27%. RBD
      has however also been described in amyotrophic lateral sclerosis, limbic
      encephalitis, Guillain-Barre syndrome, Tourette's syndrome, autism, epilepsy and
      post-traumatic stress disorder. The present paper reviews the current literature
      on symptomatic RBD and on RBD induced by drug administration, antidepressants,
      tricyclics and newer drugs, which are often described as precipitating factors
      for RBD. Controversial findings, flaws in categorisation and hypothetical
      aetiological mechanisms are also discussed.

PMID- 17235430
TI  - Restless legs syndrome: diagnosis, epidemiology, classification and consequences.
AB  - Restless legs syndrome (RLS) is a sensorimotor disorder characterised by a
      complaint of an almost irresistible urge to move the legs. RLS is diagnosed
      clinically by means of the four essential criteria of the International Restless
      Legs Syndrome Study Group. In doubtful cases, neurophysiological examinations,
      such as polysomnography and/or a suggested immobilisation test, can be performed
      to confirm a clinical suspicion of RLS. Several other conditions may present
      sensorimotor complaints with features similar to RLS; a careful sleep history is
      required to avoid a misdiagnosis. Three different scales have been validated to
      assess the severity of RLS. In the general population, RLS prevalence ranges from
      0.1% to 11.5%, with a high number of patients affected by a primary form of the
      sleep disturbance (70%-80%). However, several clinical conditions have been
      associated with RLS, such as iron deficiency, uraemia, pregnancy and
      polyneuropathy. Furthermore, recent studies show that RLS may be associated also
      to type 2 diabetes mellitus and to multiple sclerosis. RLS has a negative impact
      on sleep, cognitive functions, quality of life and mental status. Higher
      awareness of RLS among physicians is required; it remains an underdiagnosed
      clinical condition.

PMID- 17235431
TI  - Aetiopathogenesis of restless legs syndrome.
AB  - The pathogenesis of restless legs syndrome (RLS) is not yet completely
      understood. However, recent research addressed the hypothesis that dopaminergic
      pathways are involved in the mechanisms responsible for the syndrome both for
      sensory and motor symptoms. Different aspects of RLS physiopathogenesis are
      discussed: the genetic components indicating different chromosomes are
      responsible for the heterogeneity in the phenotypic expression of the familial
      forms of RLS; the neurophysiologic data showing the hyperexcitability of the
      cortico-motor efferents at supraspinal level, with spinal cord involvement
      leading to a definition of RLS as a syndrome of somatosensory misperception,
      disturbed gain regulation and/or a shifted threshold; the paucity of neuroimaging
      data, which do not definitively clarify the eventual dopaminergic dysfunction in
      RLS patients, at least at the basal ganglia level; an illustration of the
      iposideremic hypothesis starting from the therapeutic effect of iron, although
      not for all patients, and based on some neurophysiologic and neuropathologic
      results both in humans and animal models; and finally the role of the opioid
      system, suggesting an imbalance of dopamine-opiate system inputs to brain regions
      involved in motor responses and pain perception, and representing an aberrant
      behavioural response to sensory inputs. All these theories may have a final
      common pathway in the dopaminergic system, reinforcing the empirical results of
      benefit with dopamine or dopamine-agonist treatments in RLS.

PMID- 17235433
TI  - Daytime somnolence and night sleep disturbances in Parkinson's disease:
      background and future treatment prospective.
AB  - Sleep abnormalities are common in patients with Parkinson's disease (PD). Current
      clinical evidence suggests that both daytime somnolence and night-time sleep
      abnormalities are related mainly to worsening disease. Improvements in drug
      delivery, such as transdermal patch, allow more stable dopaminergic stimulation
      throughout the day. This approach might prove beneficial also for nonmotor
      symptoms and particularly helpful in improving sleep architecture in PD.

PMID- 17235432
TI  - On the pathway of an animal model for restless legs syndrome...
AB  - Restless legs syndrome (RLS) is a chronic sleep motor disorder that affects up to
      10% of the general population. Except for periodic leg movements (PLM), which can
      be found in the great majority of RLS patients, no objective hematochimic or
      neurophysiological markers are available to prove the diagnosis, which is based
      on clinical standard criteria. Nowadays, the aetiopathogenesis of the syndrome is
      unknown. In a consistent sample of patients affected by the idiopathic form, the
      disease is inherited as an autosomal dominant trait related to an unidentified
      locus, while each symptomatic form is probably linked to a specific cause.
      Although of possible different origins, both the primary and secondary forms may
      share the same pathogenetic mechanism, which, even if unclear, could be
      characterised by a neurological dysfunction of the dopaminergic system. Several
      issues, including strong efficacy of dopamine-agonist treatments, support this
      theory, which is currently considered the main pathogenetic hypothesis. Most of
      the past studies tried to clarify the RLS mechanism using the neurophysiological,
      biochemical and neuroimaging techniques applied to the field of human research.
      Now the time has come to accept the challenge in creating an animal model of RLS,
      which may emerge as a decisive step in understanding RLS pathogenesis, and to
      develop and test new therapies. Even though there have been a few significant
      efforts, a valid animal model of RLS still does not exist. In past pioneering
      studies, the authors attempted to induce restless motor behaviour in animals by
      different strategies: antidopaminergic pharmacological interventions, spinal or
      cerebral lesions of specific regions involved in the motor control and in
      dopamine regulation, and selective deletion of genes coding for dopamine
      receptors. Rodents (mice and rats) were always chosen by the authors as the
      animals for their experiments. The current tendency in achieving an RLS model is
      generally represented by simulation of a symptomatic condition of RLS or by a
      direct interference of the dopaminergic system. In this regard, the
      pharmacological method had the intention to reproduce the neuroleptic-induced
      acathisia, the spinal lesional model was based on the hypothesis of myelopathic-
      related PLM, and the hypothalamic lesion tested the motor consequence of A11
      dopaminergic neurons. Preliminary studies are underway to replicate the pregnancy
      related form of RLS by using a hormonal intervention, and the iron-deficiency
      secondary form by using specific iron-free diets. Today, modern technologies are
      available to easily replicate in animals most of the symptomatic RLS conditions.
      In addition, more than a few well validated animal models of different diseases
      known to be related to RLS or PLM, for instance, Parkinson's disease, rheumatoid
      arthritis and renal failure, could also be exploited in addressing this topic.
      The real obstacle in achieving an RLS model is the absence of a certain
      diagnostic marker to recognise if the animal that underwent the different
      experimental procedures has developed the RLS condition or not. Concerning this
      issue, possible specific endpoints are represented by the increase in locomotor
      activity, which are ascertainable by different techniques, such as openfield or
      run-wheel activity, or by sleep fragmentation, in which the circadian shift can
      be verified by applying polysomnography on the animal. PLM are probably the only
      specific and reliable markers available to recognise and quantify experimentally
      induced RLS. Despite a few authors who reported the presence of limb-phasic,
      pseudoperiodic activity during sleep in old or in lesioned rats, the existence of
      spontaneous or provoked PLM in animals is still debated. Eventually, the PLM
      features in an animal could be markedly different compared to human ones. To
      recognise and characterise PLM in animals, three more essential steps are
      required: a method to record directly, as in humans, the activity of the tibialis
      anterior (TA) muscles, a consistent amount of normative control data on the TA
      activity in healthy animals, and reliable analysis to distinguish the generic
      phasic muscular activity to a possible unambiguous PLM pattern. This review
      includes a summary and a critical discussion of the previous tentative RLS
      models, proposals for other possible animal models, and firstly the preliminary
      normative data on TA activity during sleep in normal rodents.

PMID- 17235434
TI  - The treatment of restless legs syndrome.
AB  - The objective was to provide an overview of the options for treatment of primary
      restless legs syndrome (RLS), by analysing the relevant clinical trials for RLS.
      The patients considered were those affected with primary (or idiopathic) RLS.
      Levodopa, pramipexole, ropinirole, transdermal rotigotine, pergolide and
      cabergoline all show clear evidence for efficacy in short-term treatment. Adverse
      events with these drugs are those usual for dopaminergic agents, and are usually
      mild and reversible, probably because of the relatively low doses needed.
      Augmentation, i.e., worsening of RLS symptoms not due to progression of the
      disease, however, represents a worrisome side effect of dopaminergic drugs,
      especially levodopa. Ergot-derived dopaminergic agents should also be
      periodically checked for the possible development of multivalvular heart disease
      and pleuropulmonary fibrosis. Gabapentin is another drug also having clear
      evidence for efficacy. In conclusion, dopaminergic agents represent the first
      line of treatment for idiopathic RLS.

PMID- 17235435
TI  - Periodic limb movements in sleep and periodic limb movement disorder.

PMID- 17235436
TI  - Detection of the status of tumour-infiltrating CD4+ T-cell subpopulations in
      squamous cell carcinoma of the head and neck (HNSCC) using real-time RT-PCR
      detection of CD4 mRNA.
AB  - Several studies have reported tumour infiltrating CD4(+) T cells as a favourable
      prognostic factor in some types of cancer. We investigated 37 head and neck
      squamous cell carcinomas (HNSCC) at different stages, using immunohistochemical
      staining for CD4(+) infiltrates and real-time reverse transcription polymerase
      chain reaction (RT-PCR) detection of CD4 mRNA. The CD4(+) infiltrates were
      evaluated and expressed as a percentage according to the ratio of CD4(+) T cells
      to epithelial cells in the cancer cell nests and to the overall inflammatory cell
      infiltrate in the tumor stroma. The CD4 mRNA expression level strongly correlated
      with the CD4(+) infiltration score in the cancer epithelium (r(s) = 0.858, P <
      0.001) and in the cancer stroma (r(s) = 0.797, P < 0.001). These results indicate
      that the real-time RT-PCR assay is a sensitive and reliable method for the
      detection of CD4 mRNA, and that it could be used to reassess CD4(+) infiltration
      status in resected specimens from patients with HNSCC.

PMID- 17235437
TI  - Microarray analysis reveals the role of matrix metalloproteinases in mouse
      experimental autoimmune myocarditis induced by cardiac myosin peptides.
AB  - Autoimmune myocarditis develops after the presentation of heart-specific antigens
      to autoaggressive CD4(+) T cells and after inflammation has infiltrated the
      tissues. To shed light on global changes in the gene expression of autoimmune
      myocarditis and to gain further insight into the molecular mechanisms underlying
      the genesis of myocarditis, we conducted a comprehensive microarray analysis of
      mRNA using an experimental mouse autoimmune myocarditis model via immunization
      with alpha-myosin heavy chain-derived peptides. Of over 39,000 transcripts on a
      high density oligonucleotide microarray, 466 were under-expressed and 241 over
      expressed by >or= 1.5-fold compared with the controls in BALB/C mouse with
      autoimmune myocarditis. In this paper, we list the top 50 up-regulated genes
      related to the immune response. These altered genes encode for leukocyte-specific
      markers and receptors, the histocompatibility complex, cytokines/receptors,
      chemokines/receptors, adhesion molecules, components of the complement cascade,
      and signal transduction-related molecules. Interestingly, matrix
      metalloproteinases (MMPs) such as MMP-3 and MMP-9 were up-regulated, as further
      revealed by the reverse transcriptase-polymerase chain reaction (RT-PCR) and
      immunohistochemistry assays. This indicates that MMPs may act as major regulators
      of the cytokine profile. Together, these findings provide new insight into the
      molecular events associated with the mechanism of the autoimmune genesis of
      myocarditis.

PMID- 17235438
TI  - Phenol red in the culture medium strongly affects the susceptibility of human MCF
      7 cells to roscovitine.
AB  - Estrogens play an important role in the growth and terminal differentiation of
      the mammary gland. Prolonged exposure to estrogens seems to predispose women to
      breast cancer. It recently became evident that not only the intrinsic hormonal
      status but also external factors such as the occurrence of pharmaceuticals and
      chemicals with hormone activity in the environment may put women at greater risk
      of developing breast cancer. We focused on the interference of endocrine
      disruptors in breast cancer therapy. We observed that phenol red added to the
      culture medium strongly promoted the cell proliferation and cell cycle
      progression of human cells expressing the estrogen receptor, and affected their
      susceptibility to chemotherapy.

PMID- 17235439
TI  - Increased expression of HSP70 by colon cancer cells is not always associated with
      access to the dendritic cell cross-presentation pathway.
AB  - Dendritic cells (DCs) are highly specialized antigen-presenting cells endowed
      with the unique ability to not only present exogenous antigens upon exposure to
      MHC II, but also to cross-present these upon exposure to MHC I. This property was
      exploited to generate the tumor-specific CD8 cytotoxic lymphocyte (CTL) response
      in DCs-based cancer vaccine protocols. In this context, the source of tumor
      antigens remains a critical challenge. A crude tumor in the context of danger
      signals is believed to represent an efficient source of tumor antigens (TAs) for
      DCs loading. In our previous work, increased DCs cross-presentation of antigens
      from necrotic gastric carcinoma cells paralleled up-regulation of the heat shock
      protein hsp70. We studied the expression of hsp70 on primary colon carcinoma
      cells and its relevance in the cross-priming of anti-tumor CTL by tumor-loaded
      DCs. Hsp70 was expressed on all three of the tumors studied, but was never
      detected in the peritumoral normal mucosa (NM). The uptake of the tumor induced a
      trend towards down-modulation of the monocyte-specific marker CD14, but had no
      effect on the chemokine receptors CCR4 and CCR7. The IFN-gamma enzyme-linked
      immunospot assay (ELIspot) showed cross-priming of CTL by tumor-loaded but not NM
      loaded DCs in four of the six cases studied. The CTL response generated in
      DC+tumor cultures was directed towards the tumor, but not towards NM, and it was
      characterized by refractoriness to polyclonal (Ca ionophores, PKC activators)
      stimuli. Of the three CTL-generating tumors, only one expressed hsp70. This data
      indicates a tumor-specific expression of hsp70, but does not support its
      relevance in the DC cross-presentation of TAs.

PMID- 17235440
TI  - Major depression in Chinese Americans: the roles of stress, vulnerability, and
      acculturation.
AB  - BACKGROUND: This study examined the relationship between recent negative life
      events, level of acculturation and other psychosocial risk factors in predicting
      major depression in Chinese Americans. METHOD: Data were collected on 1,747
      Chinese immigrants and native-born residents of the United States (ages 18-65)
      who resided in Los Angeles County between 1993 and 1994. RESULTS: Findings
      indicated that a positive psychiatric history increased risk for major depression
      at Time 2, while social conflicts and traumatic life events moderated the effects
      of negative life events in increasing risk for major depression. In addition,
      level of acculturation moderated the effects of recent negative events in
      increasing risk, but only for those who were more highly acculturated.
      CONCLUSIONS: The importance of testing the cross-cultural applicability of the
      stress-vulnerability hypothesis among ethnic minorities and extending them to
      include immigrant vulnerabilities is discussed.

PMID- 17235441
TI  - Economic costs of depression in China.
AB  - BACKGROUND: A recent survey in China indicated the 12-month prevalence rate of
      depressive disorders was 2.5% in Beijing and 1.7% in Shanghai. These disorders
      may result in disability, premature death, and severe suffering of those affected
      and their families. AIMS: This study estimates the economic consequences of
      depressive disorders in China. METHODS: Depressive disorders can have both direct
      and indirect costs. To obtain direct costs, the research team interviewed 505
      patients with depressive disorders and their caregivers in eight
      clinics/hospitals in five cities in China. Depression-related suicide rates were
      obtained from published literature. The human capital approach was used to
      estimate indirect costs. Epidemiological data were taken from available
      literature. RESULTS: The total estimated cost of depression in China is 51,370
      million Renminbi (RMB) (or US $6,264 million) at 2002 prices. Direct costs were
      8,090 million RMB (or US$ 986 million), about 16% of the total cost of
      depression. Indirect costs were 43,280 million RMB (or US$ 5,278 million), about
      84% of the total cost of depression. CONCLUSIONS: Depression is a very costly
      disorder in China. The application of an effective treatment--reducing the length
      of depressive episodes (or preventing episodes) and reducing suicide rates--will
      lead to a significant reduction in the total burden resulting from depressive
      disorders. Government policymakers should seriously consider further investments
      in mental health services.

PMID- 17235442
TI  - Residential mobility of individuals with diagnosed schizophrenia: a comparison of
      single and multiple movers.
AB  - BACKGROUND: Several studies have compared the residential mobility of individuals
      with schizophrenia to mobility of individuals with other mental disorders or with
      no mental disorders. Little research has been undertaken to describe differences
      between single (i.e., infrequent) and multiple (i.e., frequent) movers with
      schizophrenia, and the association between frequency of mobility and health and
      health service use. METHODS: The data source is population-based administrative
      records from the province of Manitoba, Canada. Hospital separations and
      physicians claims are linked to health registration files to identify a cohort
      with diagnosed schizophrenia and track changes in residential postal code over
      time. Single movers (N = 736), who had only one postal code change in a 2.5-year
      observation period, are compared to multiple movers (N = 252), who had two or
      more postal code changes. Differences in demographic, socioeconomic, and
      geographic characteristics, measures of health service use, and the prevalence of
      several chronic diseases were examined using chi(2) tests, logistic regression,
      and generalized linear regression. RESULTS: Multiple movers were significantly
      more likely to be young, live in socioeconomically disadvantaged neighborhoods,
      and reside in the urban core. The prevalence of a co-occurring substance use
      disorder and arthritis was higher for multiple than single movers. Use of acute
      and ambulatory care for schizophrenia, other mental disorders, as well as
      physical disorders was generally higher for multiple than single movers.
      CONCLUSIONS: Frequency of mobility should be considered in the development of
      needs-based funding plans and service delivery interventions. Other opportunities
      to use record-linkage techniques to examine residential mobility are considered.

PMID- 17235443
TI  - Antidepressant utilization in primary care in a Spanish region: impact of generic
      and reference-based pricing policy (2000-2004).
AB  - OBJECTIVE: To describe the evolution of antidepressant use in primary care in the
      Valencian region (Spain) from 2000 to 2004 and to analyze the effects of
      reference-based price and generic drugs introduction on drug utilization and cost
      saving. METHODS: Retrospective observational study in primary care using sales
      data collected from antidepressant group (N06A), corresponding to the period 2000
      2004. Defined daily dose (DDD)/1000 inhabitants per day were obtained as
      consumption data. Cost and cost/DDD rate evolution was related to reference price
      system implantation. RESULTS: Antidepressant utilization progressively increased
      by 44.0% from 30.3 DDDs/1000 per day in 2000 to 43.5% in 2004. Selective
      serotonin reuptake inhibitors (SSRIs) comprised 77% of the total consumption
      where paroxetine, sertraline and fluoxetine were the most used drugs in 2004. The
      proportion of relative use and cost of fluoxetine declined after a reference
      price and the introduction of generic competitors were put into effect in 1999;
      cost/DDD was reduced by 1.8. Third-generation antidepressants showed a fast
      rising rate i.e. venlafaxine utilization multiplied by 2.2; this drug with the
      higher cost/DDD was not subjected to the reference price system. Reduction in
      citalopram utilization was related to a replacement by its recently marketed
      enantiomer escitalopram. CONCLUSIONS: In 2004, reference price policy and the
      implementation of generic drugs reduced the antidepressant cost by DDD. However,
      antidepressant expenditure increased since 2000 due to a continued growth in
      consumption (SSRIs and novel agents) and a displacement of prescriptions to drugs
      that were not included in the reference price policy.

PMID- 17235444
TI  - Increase in involuntary psychiatric treatment and child welfare placements in
      Finland 1996-2003. A nationwide register study.
AB  - BACKGROUND: Emotional and behavioural problems are common in young people and
      mental health problems are frequently intertwined with social problems. Both
      involuntary psychiatric treatment and taking into care may be used in order to
      manage youth behavioural problems. Compulsory interventions always endanger
      violating basic civil rights and therefore careful monitoring of them is
      warranted. AIM: The aim of this study was to evaluate trends in Finland in
      involuntary psychiatric inpatient treatment and taking into care 12- to 17-year
      old adolescents from the mid-1990s to the early 2000s. METHOD: A nationally
      representative retrospective register study of the period 1996-2003 using the
      hospital discharge register and child welfare register in Finland. RESULTS: Both
      types of compulsory interventions increased vastly during the study period. The
      numbers of involuntary psychiatric treatment periods and child welfare placements
      of adolescents varied considerably in relation to each other, and across
      different regions of the country. CONCLUSIONS: As there is no evidence of a vast
      increase in mental disorders or serious behavioural problems in young people,
      there is an obvious need for further research on reasons of the significant
      increase in the use of coercion and for the wide regional variation. Possible
      explanations discussed are different service structures and treatment cultures.

PMID- 17235445
TI  - An observational, "real life" trial of the introduction of assertive community
      treatment in a geographically defined area using clinical rather than service use
      outcome criteria.
AB  - INTRODUCTION: Assertive outreach methods of service delivery hold promise, but
      have been evaluated mostly in the context of short-lived experiments of limited
      sustainability and a focus on service use outcomes. The aim of the current
      investigation was to conduct an observational, "real life", pre-post comparison
      of the introduction of assertive outreach in a geographically defined area using
      clinical rather than service use outcome criteria. METHOD: Assertive outreach was
      implemented in 2002 in a catchment area of 250,000, where cumulative routine
      outcome measurements had been in place since 1998. Clinical outcome, defined as
      making a transition to meeting the recently introduced remission criterion, was
      compared for two non-overlapping cohorts of patients treated in the period 1998
      2001 and in the period 2002-2005. RESULTS: The proportion of patients that made
      the transition to remission increased from 19% in the period before the
      introduction of assertive outreach, to 31% in the period after (OR = 2.21, 95% CI
      1.03-4.78). CONCLUSION: Assertive outreach in real life routine clinical practice
      brings about detectable changes in clinical outcome. ACT may bring improvement to
      the lives of patients living in countries characterised by fragmented and
      hospital-based mental health services.

PMID- 17235447
TI  - 'Postconditioning' the human heart: multiple balloon inflations during primary
      angioplasty may confer cardioprotection.
AB  - Growing evidence from experimental models suggests that relief of myocardial
      ischemia in a stuttering manner (i.e., 'postconditioning' [PostC] with brief
      cycles of reperfusion-reocclusion) limits infarct size. However, the potential
      clinical efficacy of PostC has, to date,been largely unexplored. Using a
      retrospective study design, our aim was to test the hypothesis that creatine
      kinase release (CK: clinical surrogate of infarct size) would be attenuated in ST
      segment elevation myocardial infarction (STEMI) patients requiring multiple
      balloon inflations-deflations during primary angioplasty versus STEMI patients
      who received minimal balloon inflations and/or direct stenting. To investigate
      this concept, we reviewed the records of all STEMI patients with single vessel
      occlusion who presented to our institution from November 2004 - April 2006 for
      primary angioplasty. Exclusion criteria were: previous MI, cardiogenic shock,
      patients resuscitated from cardiac arrest, or pre-infarct angina. Patients were
      prospectively divided into two subsets: those receiving 1-3 balloon inflations
      (considered the minimum range to achieve patency and stent placement) versus
      those in whom 4 or more inflations were applied. Peak CK release was
      significantly lower in patients requiring > or =4 versus 1-3 inflations (1655
      versus 2272 IU/L; p<0.05), an outcome consistent with the concept that relief of
      sustained ischemia in a stuttered manner (analogous to postconditioning) may
      evoke cardioprotection in the clinical setting.

PMID- 17235446
TI  - Drinking frequency and quantity and risk of suicide among men.
AB  - BACKGROUND: Individuals who die from suicide commonly have consumed alcohol
      immediately beforehand, often in large quantities. However, prospective cohort
      data on regular alcohol use as a risk factor for suicide are lacking. METHOD: As
      part of the Health Professionals Follow-up Study, 47,654 men free of cancer
      prospectively reported their drinking habits, including average use, drinking
      frequency, and typical maximal use on repeated occasions beginning in 1986.
      Participants were followed for death to 2002. RESULTS: A total of 136 men died
      from suicide during follow-up. Quantity of alcohol consumed per drinking day
      tended to be associated with a greater risk of suicide mortality, with an
      adjusted hazard ratio among men consuming 30.0 or more grams (more than two
      drinks) per drinking day of 2.42 (95% confidence interval, 0.75-7.80; P-trend
      0.05). Average alcohol consumption, drinking frequency, and binge drinking were
      not independently associated with risk. The apparent relationship of quantity
      consumed per drinking day with risk was not substantially changed by adjustment
      for serious illness or other dietary factors and was most notable for suicide
      associated with firearm use. CONCLUSIONS: Among men, risk of death from suicide
      tends to be associated primarily with quantity of alcohol consumed per drinking
      day, not with drinking frequency or overall alcohol consumption. This finding
      supports guidelines that limit consumption among men who choose to drink alcohol
      to two drinks or less per drinking day.

PMID- 17235448
TI  - CYP17 gene polymorphism and its association with high-risk north Indian breast
      cancer patients.
AB  - A single T > C change at the 5' promoter region of the CYP17 gene is reported to
      be associated with increased risk of breast cancer. This study evaluates the
      influence of genetic polymorphism of CYP17 on breast cancer susceptibility. Two
      hundred and forty-two patients with histopathologically confirmed breast cancer
      and 212 age-matched controls were included in the present study. Information
      relating to age at onset of the disease, family history and estrogen receptor
      status was elicited. Investigation for CYP17 polymorphism was carried out in 106
      early onset, 80 late onset and 56 familial cases. The frequencies of two CYP17
      alleles were also analyzed in 116 (47.9%) cases with known estrogen receptor (ER)
      status confirmed immunohistochemically. A polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) method was used to detect the
      polymorphism, and the genotypes identified were assigned as homozygous wild type
      (A1A1), heterozygous variant (A1A2), and homozygous variant (A2A2). Associations
      between the various genotypes in patients and controls were investigated with
      Fisher's exact test. All the tests were two tailed. The results showed that the
      frequency of heterozygous and homozygous CYP17 genotype was higher in early onset
      breast cancer patients (94.3%) than in controls (80.3%), and the difference was
      significant (P = 0.001). A highly statistically significant increased risk in
      carriers of homozygous A2 allele was found in young patients (P < or = 0.001) in
      comparison with patients having late onset condition (P = 0.260). However, no
      significant association between the genotype and breast cancer risk was observed
      among women with strong family history. Further, data had showed that patients
      (80.6%) with at least one A2 allele tended to exhibit ER-independent cell
      proliferation, although statistical significance could not be established (P =
      0.160). The present findings suggest that CYP17 A2 allele gene polymorphism might
      play a significant role in breast cancer development in young Indian women.

PMID- 17235449
TI  - Frequency of the LRRK2 G2019S mutation in Italian patients affected by
      Parkinson's disease.
AB  - Mutations in the gene Leucine-Rich Repeat Kinase 2 (LRRK2) have been identified
      in both dominant and sporadic cases affected by Parkinson's disease (PD). The
      LRRK2 G2019S mutation (c.6055G>A) is the most frequent substitution in
      Caucasians, accounting for approximately 5-6% of familial and 0.5-2.0% of
      apparently sporadic PD cases. We investigated the frequency of the LRRK2 G2019S
      mutation in 98 unrelated Italian PD patients, including 12 probands belonging to
      families compatible with autosomal dominant inheritance (12%) and 86 sporadic
      cases (88%). We detected the G2019S mutation in one sporadic female patient
      (1.2%). These results confirm that the G2019S mutation is a relevant cause of
      sporadic PD cases in the Italian population and stress the importance of
      performing this genetic test, which has important implications for genetic
      counselling.

PMID- 17235451
TI  - Childhood abuse and non-suicidal self-harm behavior in adulthood among the
      mothers of children in psychiatric treatment.

PMID- 17235450
TI  - Adhesion of composite luting cement to Er:YAG-laser-treated dentin.
AB  - Although some studies claim to the increase of composite resin adhesion to Er:YAG
      laser-treated dentin, there are still no reports on the adhesion of composite
      resin cements to the irradiated surface. This in vitro study evaluated the
      tensile bond strength (TBS) of a composite resin cement to dentin treated with
      the Er:YAG laser. Sixty human dentin samples were divided into four groups (n =
      15): G1 (Control)-no treatment; G2-Er:YAG laser 60 mJ, 2 Hz, with water cooling,
      non-contact (19 J/cm(2)); G3-Er:YAG laser 60 mJ, 10 Hz, 50/10 fiber, contact,
      without water cooling (40 J/cm(2)); G4-Er:YAG laser 60 mJ, 10 Hz, 50/10 fiber,
      contact, with water cooling (40 J/cm(2)). After the surface treatment, each
      sample was submitted to bonding procedures. The analysis of variance (ANOVA) and
      Tukey tests revealed no statistical significant difference on TBS values for
      groups G1 (13.73 +/- 3.05 MPa), G2 (12.60 +/- 2.09 MPa) and G4 (11.17 +/- 4.04
      MPa). G4 was not statistically different from G3 (8.64 +/- 2.06 MPa). Er:YAG
      laser irradiation with different settings can constitute an alternative tool to
      the use of composite resin-luting cements.

PMID- 17235452
TI  - Extracellular amino acid levels in the human liver during transplantation: a
      microdialysis study from donor to recipient.
AB  - Using microdialysis, we have monitored extracellular levels of amino acids and
      related amines in the human liver at three stages of the transplantation
      procedure: donor retrieval, back table preparation and during 48 h post
      implantation. By comparing the ratio of mean levels at the donor and back table
      stages, with the ratio between early (2-6 h) and late (43-48 h) post-reperfusion,
      these amines were classified into one of three groups. In one group, back table
      levels were markedly higher than during the donor stage, with levels declining
      over time post-reperfusion. A second group had much lower levels in the back
      table than during the donor phase, and post-reperfusion levels were either stable
      or increased over time. Concentrations of amino acids in the final group remained
      relatively constant at all stages. This study illustrates the value of
      microdialysis in providing organ-specific metabolic data that may indicate
      specific mechanisms of poor graft function.

PMID- 17235453
TI  - Euk-PLoc: an ensemble classifier for large-scale eukaryotic protein subcellular
      location prediction.
AB  - With the avalanche of newly-found protein sequences emerging in the post genomic
      era, it is highly desirable to develop an automated method for fast and reliably
      identifying their subcellular locations because knowledge thus obtained can
      provide key clues for revealing their functions and understanding how they
      interact with each other in cellular networking. However, predicting subcellular
      location of eukaryotic proteins is a challenging problem, particularly when
      unknown query proteins do not have significant homology to proteins of known
      subcellular locations and when more locations need to be covered. To cope with
      the challenge, protein samples are formulated by hybridizing the information
      derived from the gene ontology database and amphiphilic pseudo amino acid
      composition. Based on such a representation, a novel ensemble hybridization
      classifier was developed by fusing many basic individual classifiers through a
      voting system. Each of these basic classifiers was engineered by the KNN (K
      Nearest Neighbor) principle. As a demonstration, a new benchmark dataset was
      constructed that covers the following 18 localizations: (1) cell wall, (2)
      centriole, (3) chloroplast, (4) cyanelle, (5) cytoplasm, (6) cytoskeleton, (7)
      endoplasmic reticulum, (8) extracell, (9) Golgi apparatus, (10) hydrogenosome,
      (11) lysosome, (12) mitochondria, (13) nucleus, (14) peroxisome, (15) plasma
      membrane, (16) plastid, (17) spindle pole body, and (18) vacuole. To avoid the
      homology bias, none of the proteins included has > or =25% sequence identity to
      any other in a same subcellular location. The overall success rates thus obtained
      via the 5-fold and jackknife cross-validation tests were 81.6 and 80.3%,
      respectively, which were 40-50% higher than those performed by the other existing
      methods on the same strict dataset. The powerful predictor, named "Euk-PLoc", is
      available as a web-server at http://202.120.37.186/bioinf/euk . Furthermore, to
      support the need of people working in the relevant areas, a downloadable file
      will be provided at the same website to list the results predicted by Euk-PLoc
      for all eukaryotic protein entries (excluding fragments) in Swiss-Prot database
      that do not have subcellular location annotations or are annotated as being
      uncertain. The large-scale results will be updated twice a year to include the
      new entries of eukaryotic proteins and reflect the continuous development of Euk
      PLoc.

PMID- 17235454
TI  - Prediction of protein subcellular localization by support vector machines using
      multi-scale energy and pseudo amino acid composition.
AB  - As more and more genomes have been discovered in recent years, there is an urgent
      need to develop a reliable method to predict the subcellular localization for the
      explosion of newly found proteins. However, many well-known prediction methods
      based on amino acid composition have problems utilizing the sequence-order
      information. Here, based on the concept of Chou's pseudo amino acid composition
      (PseAA), a new feature extraction method, the multi-scale energy (MSE) approach,
      is introduced to incorporate the sequence-order information. First, a protein
      sequence was mapped to a digital signal using the amino acid index. Then, by
      wavelet transform, the mapped signal was broken down into several scales in which
      the energy factors were calculated and further formed into an MSE feature vector.
      Following this, combining this MSE feature vector with amino acid composition
      (AA), we constructed a series of MSEPseAA feature vectors to represent the
      protein subcellular localization sequences. Finally, according to a new kind of
      normalization approach, the MSEPseAA feature vectors were normalized to form the
      improved MSEPseAA vectors, named as IEPseAA. Using the technique of IEPseAA, C
      support vector machine (C-SVM) and three multi-class SVMs strategies, quite
      promising results were obtained, indicating that MSE is quite effective in
      reflecting the sequence-order effects and might become a useful tool for
      predicting the other attributes of proteins as well.

PMID- 17235455
TI  - PTEN down regulates AP-1 and targets c-fos in human glioma cells via PI3
      kinase/Akt pathway.
AB  - The continual activation of signaling cascades results in dramatic consequences
      that include loss of cellular growth control and neoplastic transformation. We
      show here that phosphoinositide 3-kinase and its mediator Akt was constitutively
      activated in glioma and that this might be due to the aberrant expression of
      their natural antagonist PTEN. The PTEN (phosphatase and tensin homologue deleted
      on chromosome ten) tumor suppressor gene modulates cell growth and survival
      through mechanisms that are incompletely understood. In this study, we
      investigated the possibility that PTEN mediates its effects through modulation of
      transcription factor AP-1, which is in part due to decrease in c-fos expression
      which was dependent on PI3kinase activity. Consistent with a reduction in the c
      fos levels, an AP-1 dependent reporter gene was poorly induced in the PTEN
      expressing cell lines. In contrast to its effect on c-fos, PTEN did not affect
      the expression of c-Jun and other fos family members. We also show that the
      effect of PTEN on c-fos expression was due to its ability to antagonize PI3
      kinase and could be mimicked by the expression of dominant negative Akt mutant.
      Taken together, these data indicate that the aberrant expression of PTEN
      contributes to the activation of the PI3kinase/Akt pathway and its transcription
      factor mediators in glioma. We conclude that the ectopic expression of PTEN down
      regulates the proliferation of glioma cells through the suppression of AP-1 and
      that this target might be essential for its central role in the growth and
      survival of glioma cancer cells.

PMID- 17235456
TI  - An evidence-based approach to the treatment of thyroid lymphoma.
AB  - BACKGROUND: Primary thyroid lymphoma is a rare tumor that makes up 1-5% of
      thyroid malignancies and less than 2% of extranodal lymphomas. The treatment and
      prognosis of thyroid lymphomas can be divided into two distinct clinicopathologic
      entities: pure mucosa-associated lymphoid tissue (MALT) lymphomas and diffuse
      large B-cell or mixed subtypes. METHODS: An evidence-based review was performed
      to determine the role of fine-needle aspiration (FNA) biopsy and adjuncts as the
      first diagnostic test for thyroid lymphoma, the role of open surgical biopsy, the
      role of palliative surgery as well as the best treatment (combined chemoradiation
      versus single modality surgery or radiation) for thyroid lymphoma. The ideal
      treatment of thyroid lymphoma was further assessed for both diffuse B-cell and
      MALT histologic subtypes. RESULTS: Although an evidence-based review was
      challenging primarily due to a lack of high-level evidence, several
      recommendations are possible and presented regarding the optimal diagnostic
      methods and treatment of thyroid lymphoma. FNA and adjuncts are recommended as
      the first test to diagnose thyroid lymphoma, but open surgical biopsy may still
      be required in many cases. Combined chemoradiation therapy is recommended for all
      diffuse B-cell or mixed lymphomas. Single modality therapy with surgery or
      radiation alone may be considered for early-stage (IE) intrathyroidal MALT
      lymphomas. No recommendations could be made regarding the role of palliative
      surgery. CONCLUSION: Evidence-based recommendations can be applied to the
      individual patient with thyroid lymphoma with the involvement of an experienced
      multidisciplinary team consisting of an endocrine/oncology surgeon, radiation
      oncologist, and medical oncologist.

PMID- 17235458
TI  - A new face by combined surgery for patients with complex dentofacial deformity.
AB  - BACKGROUND: This article aims to present and discuss 53 patients who received a
      new identity because of major changes to the face after treatment with
      bimaxillary osteotomy, concomitant maxillomalar augmentation, genioplasty, and
      rhinoplastic procedures for their complex dentofacial skeletal deformity and
      class 3 malocclusion. METHODS: During a 12-year period (January 1993 to April
      2005), more than 500 patients with dentofacial deformities and malocclusions have
      undergone orthognathic surgery performed by a team consisting of the same plastic
      surgeons and orthodontists. Among this group, 53 patients (30 women and 23 men)
      underwent surgery for both aesthetic and functional concerns. The mean patient
      age was 20.4 years (range, 17-28 years). All the patients were treated with
      bimaxillary osteotomy, concomitant maxillomalar augmentation, osseous
      genioplasty, and rhinoplastic procedures in the same session. The patients were
      followed 12 to 44 months by the plastic surgeon, and at least 1 year by the
      orthodontist. RESULTS: There was no orthognathic relapse or other major
      complications requiring reoperation. There was prolonged nerve anesthesia or
      hypoesthesia that resolved within 6 months for 4 patients (7.5%), a short period
      of anesthesia or hypoesthesia that resolved within 4 weeks for 11 patients
      (20.7%), a wide alar base in 3 patients, and a slight deviation of the cartilage
      septum in 2 patients. CONCLUSION: In one session, five different procedures can
      be performed without any problem, each of which can produce major changes to the
      face while maintaining the whole facial harmony. The authors determined that
      these dramatic positive outcomes for the combined procedure can easily be
      tolerated and accepted by all their patients. However, the patients have had
      difficulty with their family or friends accepting their new appearance, and even
      have had to change their photos on identification cards. This is encouraging for
      the management of new patients in the future.

PMID- 17235457
TI  - Juvenile polyp in Thai children--clinical and colonoscopic presentation.
AB  - BACKGROUND: The aim of this prospective study was to describe the clinical
      characteristics of colorectal polyp in Thai children. METHODS: From December 2002
      to February 2005, children under 15 years of age presenting with rectal bleeding
      were prospectively enrolled. Demographic, clinical, and laboratory information
      was recorded. Location, number, characteristics, and histopathology of the polyps
      were noted. RESULTS: There were 32 patients with a mean age of 6.5 years. The
      most common presenting symptom was hematochezia, followed by prolapsing rectal
      mass and diarrhea. In 20 patients there was a single polyp, 6 had 2-4 polyps, and
      6 were diagnosed with polyposis coli. Most of the polyps were located exclusively
      at the rectum and sigmoid colon. In only 7 cases were the polyps proximal to the
      rectosigmoid region. This included 6 patients who had polyps beyond the splenic
      flexure. All were juvenile polyps without evidence of adenomatous changes.
      Compared to those with isolated polyps, the patients with polyposis coli had a
      statistically significant incidence of right-sided polyps (P <0.001) and a
      history of prolapse of the rectal mass (P = 0.006). CONCLUSIONS: Because of the
      high prevalence of right-sided polyps and the concern about malignant
      transformation, colonoscopy should be considered as the initial evaluation in
      children with rectal bleeding.

PMID- 17235459
TI  - Radiofrequency volume reduction of gastrocnemius muscle hypertrophy for cosmetic
      purposes.
AB  - Muscularly prominent calves, caused mainly by hypertrophy of the gastrocnemius
      muscle (GCM), are prevalent among Asian women, and this condition can be a
      significant factor leading to psychological stress. The authors have devised a
      method for contouring the calf using radiofrequency (RF) applications to the GCMs
      to correct thick, muscular legs. This study was performed to investigate the
      effects of RF energy in reducing enlarged GCMs for 250 patients (249 women and 1
      man) who sought aesthetic consultation for problems such as thick, muscular,
      asymmetric, or bowed calves. The operations were performed from June 2004 to
      April 2006. The patients first received a local anesthetic and sedation. After
      application of RF current, the prominent muscular contours improved, and the GCMs
      were contoured to an appropriate proportional volume. The range of the reductions
      in the calf circumferences at their thickest levels was 1 to 6 cm (mean, 2.5 cm)
      during the follow-up visits 6 months after the procedures. Most of the patients
      could return to their activities of daily living, except for exercise, after 1 to
      7 days, and they were satisfied with the improved aesthetic contour lines of
      their lower legs. Clinical photography and ultrasonic examination were performed,
      and the leg circumferences were measured. Radiofrequency-induced coagulation
      tissue necrosis of the muscles caused no functional disabilities, and the
      clinical improvement was well maintained after the treatments for up to 17 months
      of follow-up evaluation.

PMID- 17235460
TI  - Radiofrequency volumetric reduction for masseteric hypertrophy.
AB  - Masseteric hypertrophy occurs frequently among Asians, including Koreans, because
      of racial characteristics and dietary habits. It is thought to be an unpleasant
      feature, especially because of its strong and masculine impression. Recently, the
      authors developed a method for the volumetric reduction of hypertrophied masseter
      muscles using radiofrequency energy to correct the squared facial appearance
      caused by the hypertrophy. This study was performed to investigate the effects of
      radiofrequency applied to reduce hypertrophied masseter muscles of patients who
      sought an aesthetic alternative for a slim, smooth, and feminine-looking lower
      facial contour. A total of 340 patients were treated. The patients usually
      recognized the volume change 3 to 6 weeks after treatment, and an objective
      volume reduction was observed within 3 months of the operation. The range of the
      reduction in the masseter thickness, as measured by ultrasonic examination at a 6
      month postoperative follow-up visit, was 10% to 60% (mean, 27%). Most of the
      patients could eat a nearly normal diet after 4 weeks and were satisfied with the
      improved aesthetic contour lines of their lower face. Radiofrequency-induced
      coagulation tissue necrosis of the masseter did not cause any infections or
      limitations of mouth opening, and the clinical improvement was well maintained
      after the treatment.

PMID- 17235461
TI  - Attractiveness of eyebrow position and shape in females depends on the age of the
      beholder.
AB  - BACKGROUND: Great diversity exists among individuals with respect to eyebrow
      position and shape, and the notion of an "ideal" eyebrow has changed quite
      significantly over the past several decades. METHODS: This study compared three
      different variations of eyebrows. One variation was the arched eyebrow with the
      maximum height in the middle. The other two variations had their maximum height
      in the lateral third, but differed in their position (high vs low). For each of
      the seven female portraits presented, three variations were generated using
      morphing software. A total of 357 subjects 12 to 85 years of age compared these
      variations and ranked each woman individually with respect to perceived
      attractiveness. RESULTS: The data show that the preference for a specific eyebrow
      shape depends on a person's age. Young subjects up to 30 years of age preferred
      eyebrows in a lower position, and ruled out arched eyebrows. Subjects older than
      50 years stated exactly the opposite preference. CONCLUSION: First, there is not
      one single beauty ideal for eyebrows, but at least three. The ideal a person
      prefers depends on his or her age. Second, because trends are generally
      introduced by young people and not by older individuals, and the young tend to
      prefer eyebrows in a lower position, it seems plausible to assume that the trend
      currently appears to be moving away from arched eyebrows toward lower positioned
      eyebrows with a maximum height in the lateral third.

PMID- 17235463
TI  - Complete submuscular breast augmentation: 650 cases managed using an alternative
      surgical technique.
AB  - BACKGROUND: An alternative complete submuscular surgical technique for primary
      breast augmentation is presented. Since 1998, the author has refined the
      procedure for total submuscular placement of textured silicone gel implants, with
      good results for more than 650 patients. METHODS: The submuscular plane is
      accessed via a semicircular periareolar incision. Round or anatomic implants are
      placed beneath the pectoralis major and external oblique muscles, the rectus
      sheath, and the serratus anterior muscle fascia, which together create a
      contiguous structure that completely separates the implant from the breast
      tissue. RESULTS: High-riding implants were the main complication in early cases,
      through creation of an insufficiently large submuscular pocket. Only a very low
      incidence of Baker II capsular fibrosis was observed, and there were no Baker III
      or IV capsular contracture revisions. There were no cases of infection or
      "bottoming out." Areolar scarring was well concealed, and rippling and implant
      distortion were virtually nonexistent. Even in thin women, the implant edge was
      scarcely visible or palpable. Patient satisfaction levels were very high, with
      the majority viewing the implants as their own tissue in terms of natural feel
      and appearance. CONCLUSIONS: The advantages of the described surgical method are
      several-fold, particularly for lean patients. It offers a promising alternative
      to subglandular and partial submuscular implant placement and to other total
      submuscular techniques for primary breast augmentation. Furthermore, it provides
      a solution for tuberous and ptotic breasts, coupled with mastopexy as required,
      and good results have been achieved with correctional surgery for subglandular
      capsular contracture, bottoming out, and rippling.

PMID- 17235464
TI  - Nipple invagination: the umbrella effect.
AB  - The authors present their technique for correction of invaginated nipple, a
      procedure used for the past 20 years. Most often, this condition is a consequence
      of a subareolar muscle diastasis associated with short fibrous septa as well as
      short and fibrotic ducts. The correction technique specifically divides the
      fibrous tracts and corrects the diastasis of the subareolar muscle. The procedure
      was performed for healthy patients as well as for patients with mastitis sequel
      treatment and surgical reduction or augmentation mammaplasty.

PMID- 17235465
TI  - Rhinoplasty and hemophilia A.
AB  - Major surgical procedures can be performed safely for hemophiliacs provided the
      clotting factors are adequate. However, rhinoplasty, an elective facial
      procedure, has not yet been evaluated in this group of patients. The authors
      present a hemophilia A patient who underwent rhinoplasty for cosmetic reasons.

PMID- 17235467
TI  - Reconstructive rhytidectomy?
AB  - Muscular dystrophies are commonly considered hereditary progressive degenerative
      diseases that affect skeletal and cardiac muscles. Oculopharyngeal muscular
      dystrophy is a rare hereditary disorder of later onset consisting of progressive
      dysphagia and bilateral blepharoptosis unlike the peripheral muscular weakness
      common to other muscular dystrophies. The symptoms of progressive dysphagia, with
      bilateral ptosis, usually occur after the age of 40 years. The authors present a
      patient with oculopharyngeal muscular dystrophy and chronic facial pain relieved
      by midface soft tissue support, namely, the reconstructive rhytidectomy.

PMID- 17235466
TI  - A modified excision for combined reduction mammoplasty and breast conservation
      therapy in the treatment of breast cancer.
AB  - Wide local excision combined with postoperative radiotherapy is a useful
      technique for patients with breast cancer. For patients with macromastia whose
      tumor is situated in the lower pole of the breast, a breast reduction
      (keyhole?inverted T pattern) can be used to achieve wide local excision. However,
      for patients whose tumor is not in the inferior portion of the breast, and in
      whom this cancer also is situated close to the skin (requiring excision of skin
      with a 1-cm margin for oncologic safety), the traditional keyhole pattern cannot
      be used. A modification of the keyhole pattern?inverted T is described. The
      pedicle used depends on the site of the tumor. Although the breast scars are in
      different positions, a similar breast shape as well as symmetry still can be
      achieved. This is a useful technique for a select subgroup of patients. The
      outcomes for three patients are presented.

PMID- 17235470
TI  - Diffusion-induced growth of compositional heterogeneity in polymer blends
      containing random copolymers.
AB  - The compositional relaxation in random copolymer systems on a macroscopic scale
      is considered in theory. A set of diffusion equations is derived that describes
      the motion of chains of different composition and then converted into coupled
      equations for statistical moments of the compositional distribution. Several ways
      to solve the closure problem for these equations are discussed. The simplest is
      the situation when the shape of the transient compositional distribution can be
      predicted a priori, for example, a bimodal distribution is kept during
      interdiffusion of two copolymers that are not very close in composition. For a
      general case, it is shown that the cumulant-neglect closure based on the
      truncation of high-order cumulants is an effective method to get an approximate
      solution in terms of the time-dependent local mean composition and its
      dispersion. This method is applied to non-homogeneous compatible polymer systems,
      such as a random copolymer AB of a composition varying in space, a bilayer of
      Bernoullian copolymers AB of different composition, and a bilayer of homopolymers
      A and B, in which an autocatalytic polymer-analogous reaction A --> B takes
      place, with possibility of the neighbor group effect. It is found that the
      interdiffusion can lead to a substantial broadening of the local compositional
      distribution, which, in turn, accelerates the system dynamics and promotes
      chemical reactions.

PMID- 17235471
TI  - Chain orientation in natural rubber, Part II: 2H-NMR study.
AB  - Stress-induced crystallisation (SIC) and stress-induced melting (SIM) in natural
      rubbers (NR), unfilled and filled with carbon black (CB) have been studied by
      (2)H-NMR measurements. Various materials have been swollen with small amount (<
      2%) of deuterated alkane chains. The orientation of the amorphous chains, then
      the local deformation of the amorphous chains during deformation cycles and
      during stress relaxation, permits to clarify the SIC and SIM processes during
      hardening and recovery. By mechanical, WAXS and NMR measurements one determines
      the same critical draw ratio for appearance lambda(A) and disappearance lambda(E)
      of the crystallites. It is demonstrated that the hysteresis observed by the
      different techniques (stress sigma, crystallinity chi, NMR splitting Deltanu) are
      due to the supercooling effect ( lambda(A) > lambda(E), at constant temperature).
      During hardening at constant strain rate it is found that the local draw ratio
      remains constant and equal to lambda(A), whereas the crystallinity increases
      linearly with the macroscopic draw ratio lambda. The hardening sigma
      approximately (lambda - lambda(A))(2) is then interpreted as a reinforcement
      effect due to the crystallites, which act as new crosslinks. This confirms the
      prediction of Flory. In filled rubber the same effects are observed, and the
      stress amplification factor is determined as a function of the CB content. It is
      found that the fillers act as nucleation centres for the NR crystallites. The
      reinforcement of such materials is due principally to this nucleation effect and
      to the presence of a super network formed by both the NR crystallites and the CB
      fillers.

PMID- 17235473
TI  - [Motivation and barriers to participation in clinical trials].
AB  - BACKGROUND: Clinical trials are essential in clinically orientated medical
      research. Enrollment of patients is determined by patient-related barriers,
      protocol-related barriers, and motivation and behavior of the physician. MAIN
      THESES: Patients enrollment in clinical trials is determined by disease, possible
      diagnostic or therapeutic benefit of study procedures, effort of protocol
      procedures, and trust of the relationship between the physician and patient.
      Randomized trials, extensive study procedures and the possibility of receiving
      placebo are barriers to participation. Understanding of the communication process
      and knowledge of patients' needs are the base education to gain patients'
      informed consent to enter a clinical trial and a stable compliance in the course
      of the study. Motivation of physicians to enroll patients in a clinical trial is
      determined, e. g., by environmental conditions in clinic or doctors' office, the
      time and effort of study procedures, and individual academic interest.
      CONCLUSION: Awareness of factors (positive and negative) which influence
      motivation of participation in a clinical trial is useful to provide strategies
      for successful enrollment of patients.

PMID- 17235472
TI  - Does the beta-blocker nebivolol increase coronary flow reserve?
AB  - INTRODUCTION: Nebivolol, a highly selective beta1-adrenergic receptor-blocker,
      increases basal and stimulated endothelial nitric oxide (NO)-release. It is
      unknown, whether coronary perfusion is improved by the increase in NO
      availability. Therefore, we sought to evaluate the effect of nebivolol on
      coronary flow reserve (CFR) and collateral flow. METHODS: Doppler-flow wire
      derived coronary flow velocity measurements were obtained in ten controls and
      eight patients with coronary artery disease (CAD) at rest and after intracoronary
      nebivolol. CFR was defined as maximal flow during adenosine-induced hyperemia
      divided by resting flow. In the CAD group, collateral flow was determined after
      dilatation of a flow-limiting coronary stenosis. Collateral flow index (CFI) was
      defined as the ratio of flow velocity during balloon inflation divided by resting
      flow. RESULTS: CFR at rest was 3.0+/-0.6 in controls and 2.1+/-0.4 in CAD
      patients. After intracoronary doses of 0.1, 0.25, and 0.5 mg nebivolol, CFR
      increased to 3.4+/-0.7, 3.9+/-0.9, and 4.0+/-0.1 (p<0.01) in controls, and to
      2.3+/-0.7, 2.6+/-0.9, and 2.6+/-0.5 (p<0.05) in CAD patients. CFI decreased
      significantly with intracoronary nebivolol and correlated to changes in heart
      rate (r=0.75, p<0.001) and rate-pressure product (r=0.59, p=0.001). DISCUSSION:
      Intracoronary nebivolol is associated with a significant increase in CFR due to
      reduction in resting flow (controls), or due to an increase in maximal coronary
      flow (CAD patients). CFI decreased with nebivolol parallel to the reduction in
      myocardial oxygen consumption.

PMID- 17235474
TI  - [Sleep apnea--treatment improves hypertension].
AB  - Obstructive sleep apnea and arterial hypertension are frequent diseases, but they
      are also often overlooked. There is a causal relationship of sleep apnea and
      hypertension. Undiagnosed sleep apnea is probably the most important reason for
      "essential" hypertension. It is important to identify these patients. All
      hypertensive patients should be asked for snoring, breathing arrest and daytime
      sleepiness, neck circumference should be measured, and an ambulant sleep apnea
      monitoring should be performed, if necessary. Especially patients with refractory
      hypertension or non-dippers should be screened for sleep apnea and patients with
      sleep apnea should be examined for arterial hypertension. Continuous positive
      airway pressure (CPAP) can effectively lower blood pressure in the hypertensive
      sleep apnea patient. This is especially true for the obstructive sleep apnea
      patient with refractory hypertension. CPAP therapy is probably the best therapy
      for sleep apnea-induced nocturnal blood pressure rises.

PMID- 17235475
TI  - [Treatment costs of otogenic vertigo].
AB  - PURPOSE: In this decision-tree analysis, the costs of otogenic vertigo treatment
      were investigated from the third-party payer's perspective. Either the
      combination preparation, with cinnarizine 20 mg and dimenhydrinate 40 mg as
      active substances, or betahistine (12 mg betahistinedimesilate) was administered.
      METHODS: A core model, based on clinical studies, was developed and a cost
      effectiveness analysis was conducted. Both differences in effectiveness of the
      alternative treatments and adverse reactions and side effects were included. The
      number of cases, in which no more symptoms of dizziness were detected after 4
      weeks of therapy, served as the effectiveness parameter. RESULTS: The
      effectiveness-adjusted costs amounted to 130.11 Euros for patients treated with
      the combination preparation and 629.28 Euros for treatment with betahistine.
      CONCLUSION: From the third-party payer's perspective, therapy of otogenic vertigo
      with the combination preparation is more cost-effective than a treatment with
      betahistine. From the patient's perspective, the higher effectiveness and the
      superior profile of side effects militate in favor of a therapy with the
      combination preparation.

PMID- 17235476
TI  - [Effects of alcohol. Besides its harmful health impact, are there any positive
      aspects of chronic alcohol consumption?].
AB  - It is well known that chronic alcohol consumption results in a great number of
      alcohol-associated diseases. In the past 15 years, data showing a protective
      effect of chronic alcohol consumption have been published, especially with
      respect to coronary heart disease and ischemic stroke. Already small quantities
      of alcohol seem to have this protective effect which depends on various
      individual factors. This is specially pronounced in the elderly and in
      individuals with additional risk factors for coronary heart disease. An
      investigation of the German Ministry of Health has clearly shown that poor-risk
      doses of alcohol in healthy adults are <20 g alcohol per day in men and <10 g/day
      in women. Recommendations of the "German Hauptstelle fur Suchtfragen" are based
      on these data. The present review tries to critically question the protective
      effect of alcohol on arteriosclerosis. A public recommendation of alcohol as a
      coronary therapeutic agent would create more damage than benefit. A
      recommendation of alcohol as protection against myocardial infarction and
      ischemic stroke cannot be given due to its potential damaging effect on various
      other organs. In addition, a regular daily administration of alcohol should not
      be recommended.

PMID- 17235477
TI  - [German Disease Management Guideline Asthma 2005. A summary].

PMID- 17235478
TI  - [First manifestation of multiple myeloma as lethal streptococcal sepsis].
AB  - BACKGROUND: The multiple myeloma has the highest incidence among tumors of the
      bone and the bone marrow. Due to its rather mild and uncharacteristic clinical
      onset, first diagnosis of multiple myeloma is often delayed. CASE REPORT: The
      case of a 60-year-old female patient is reported who had been admitted to the
      authors' hospital in a state of severe septicemia. The patient's medical history
      had been unremarkable, apart from osteoporotic complaints. Smears of both
      peripheral blood as well as bone marrow samples showed a massive streptococcal
      infestation as demonstrated by light microscopy. In addition, plasma cells were
      the dominant cell type in these samples allowing the diagnosis of a yet unknown
      full-blown multiple myeloma. CONCLUSION: The case suggests that in the event of
      indistinct bone ache, a routine serum electrophoresis is advisable to minimize
      the risk of missing an underlying multiple myeloma.

PMID- 17235479
TI  - [Microarrays and gene expression profiling for the diagnosis in leukemia. From
      research studies to routine application].
AB  - So far, the diagnosis in leukemia is based on cytomorphology and cytochemistry,
      multiparameter flow cytometry, combined with cytogenetics, fluorescence in situ
      hybridization, and polymerase chain reaction (PCR). This allows classification
      and definition of biologically defined and prognostically relevant subtypes in
      nearly all cases. It led also in same subgroups to targeted treatment approaches.
      Today, microarray technology enables us to quantify simultaneously the expression
      status of many ten thousands of genes in one single experiment. This novel tool
      seems able to renew the diagnosis and classification in leukemia and may even
      become essential for the molecular classification of leukemias in the near
      future. An ongoing international study (MILE study) is testing the accuracy,
      sensibility and specificity of gene expression profiling in leukemia diagnostics.
      First results and future directions will be given in the article.

PMID- 17235480
TI  - [Reimbursement of patients with acute coronary syndromes in the German diagnosis
      related groups systems. Part 1: Basics and reimbursement in the case of
      conservative treatment].

PMID- 17235481
TI  - Myocardial and hepatic T2* magnetic resonance evaluation in ex-thalassemic
      patients after bone-marrow transplantation.
AB  - Bone marrow transplantation (BMT) is the only complete cure for b-thalassemia.
      Iron depletion therapy is still required to remove excess iron, accumulated
      before BMT. Hepatic and myocardial iron load were evaluated using T2* magnetic
      resonance in 8 ex-thalassemic patients after BMT, aged 19.5 +/- 4.25 years, who
      were in iron depletion therapy. Average hepatic T2* was 18.8 +/- 11.0 msec (4.1
      35.0 msec). In 4 out of 8 patients iron overload was detected, not exceeding
      however 4 mg/gr dry tissue. Average heart T2* was 31.0 +/- 4.6 msec (25.6-35.2
      msec), not significantly different (P = 0.18) from our age-matched normal
      population (33.0 +/- 4.0). Normal left ventricular ejection fraction was found in
      7 out of 8 patients (mean 64.5 +/- 7.0%) with the remaining having a marginal
      value of 54.1%. Ferritin level before BMT was 1748 +/- 451 mug/l and dropped to
      536 +/- 260 microg/l at the end of iron depletion therapy after BMT. Current
      ferritin level was 271 +/- 253 microg/l and although it was significant lower
      compared to both ferritin before BMT (P < 0.001) and after iron depletion (P <
      0.001), evidence of residual hepatic iron load was identified by T2*. Hepatic and
      myocardial T2* magnetic resonance can be used as a more reliable index than
      ferritin for evaluation of iron depletion therapy in ex-thalassemic patients
      after BMT.

PMID- 17235482
TI  - Two new species of Trichoderma from Yunnan, China.
AB  - Two new species of the fungal genus Trichoderma, Trichoderma compactum and
      Trichoderma yunnanense, isolated from rhizosphere of tobacco in Yunnan Province,
      China are described based on morphological characters and phylogenetic analyses
      of nucleotide sequences. Our DNA sequences included the internal transcribed
      spacer (ITS) regions of the rDNA cluster (ITS1 and ITS2), and partial sequences
      of the translation elongation factor 1-alpha (tef1) and a fragment of the gene
      coding for endochitinase 42 (ech42). The analyses show that T. compactum belongs
      to the Harzianum clade, and T. yunnanense belongs to the Hamatum clade.

PMID- 17235483
TI  - Synergistic bactericidal activity of Eremanthus erythropappus oil or beta
      bisabolene with ampicillin against Staphylococcus aureus.
AB  - The activity of Eremanthus erythropappus oil (EO) and some of its compounds and
      their potential synergistic interaction with ampicillin against different strains
      of Staphylococcus aureus were investigated. Determination of chemical composition
      of EO by gas chromatography-mass spectrometry (GC/MS) and bioguided chemical
      fractionation led to the identification of beta-bisabolene as the main active
      compound. A synergistic bactericidal activity of EO or beta-bisabolene with
      ampicillin against Staphylococcus aureus was observed in a time-kill assay. EO
      and beta- bisabolene have the potential to restore the effectiveness of
      ampicillin against resistant S. aureus.

PMID- 17235484
TI  - A procedure for NEPA assessment of selenium hazards associated with mining.
AB  - This paper gives step-by-step instructions for assessing aquatic selenium hazards
      associated with mining. The procedure was developed to provide the U.S. Forest
      Service with a proactive capability for determining the risk of selenium
      pollution when it reviews mine permit applications in accordance with the
      National Environmental Policy Act (NEPA). The procedural framework is constructed
      in a decision-tree format in order to guide users through the various steps,
      provide a logical sequence for completing individual tasks, and identify key
      decision points. There are five major components designed to gather information
      on operational parameters of the proposed mine as well as key aspects of the
      physical, chemical, and biological environment surrounding it--geological
      assessment, mine operation assessment, hydrological assessment, biological
      assessment, and hazard assessment. Validation tests conducted at three mines
      where selenium pollution has occurred confirmed that the procedure will
      accurately predict ecological risks. In each case, it correctly identified and
      quantified selenium hazard, and indicated the steps needed to reduce this hazard
      to an acceptable level. By utilizing the procedure, NEPA workers can be confident
      in their ability to understand the risk of aquatic selenium pollution and take
      appropriate action. Although the procedure was developed for the Forest Service
      it should also be useful to other federal land management agencies that conduct
      NEPA assessments, as well as regulatory agencies responsible for issuing coal
      mining permits under the authority of the Surface Mining Control and Reclamation
      Act (SMCRA) and associated Section 401 water quality certification under the
      Clean Water Act. Mining companies will also benefit from the application of this
      procedure because priority selenium sources can be identified in relation to
      specific mine operating parameters. The procedure will reveal the point(s) at
      which there is a need to modify operating conditions to meet environmental
      quality goals. By recognizing concerns early in the NEPA process, it may be
      possible for a mining company to match operational parameters with environmental
      requirements, thereby increasing the likelihood that the permit application will
      be approved.

PMID- 17235485
TI  - Acute renal failure in a patient with severe hemolysis.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disorder of bone marrow. It
      is characterized by blood cells lacking membrane proteins that are normally
      attached by the glycosylphosphatidylinositol (GPI) anchor. The cellular defect
      arises in a hematopoetic stem cell and is due to somatic mutation of the
      Phosphatidylinositol-glycan protein-A gene (PIG-A gene), encoding a protein
      needed for the biosynthesis of the anchor GPI. Paroxysmal nocturnal
      hemoglobinuria is presented by intravascular hemolysis, cytopenias, frequent
      infections, bone marrow hypoplasia, and a high incidence of life threatening
      venous thrombosis. Kidney involvement is usually benign and secondary to chronic
      tubular deposition of hemosiderin. Acute renal failure may occur in association
      with a hemolytic crisis. Here we report a case of 40-year-old woman with
      hematuria, pancytopenia, and acute renal failure due to PNH.

PMID- 17235486
TI  - Recombinant protein production by large-scale transient gene expression in
      mammalian cells: state of the art and future perspectives.
AB  - The expansion of the biologics pipeline depends on the identification of
      candidate proteins for clinical trials. Speed is one of the critical issues, and
      the rapid production of high quality, research-grade material for preclinical
      studies by transient gene expression (TGE) is addressing this factor in an
      impressive way: following DNA transfection, the production phase for TGE is
      usually 2-10 days. Recombinant proteins (r-proteins) produced by TGE can
      therefore enter the drug development and screening process in a very short time-
      weeks. With "classical" approaches to protein expression from mammalian cells, it
      takes months to establish a productive host cell line. This article summarizes
      efforts in industry and academia to use TGE to produce tens to hundreds of
      milligrams of r-proteins for either fundamental research or preclinical studies.

PMID- 17235487
TI  - Solubilization of enzymes in water-in-oil microemulsions and their rapid and
      efficient release through use of a pH-degradable surfactant.
AB  - alpha-Chymotrypsin and lysozyme were solubilized in a water/O-[(2-tridecyl, 2
      ethyl-1,3-dioxolan-4-yl)methoxy]-O'-methoxy poly(ethylene glycol) (CK-2,13
      surfactant)/isooctane water-in-oil microemulsion solution at 1.5-2 and 10 g l(-1)
      for 0.15 and 1.2 M: CK-2,13, respectively. Upon contact with an equal volume of
      0.1 M: NaH(2)PO(4)/Na(2)HPO(4) buffer, pH 5, a three-phase system (Winsor-III
      system) was formed, consisting of a surfactant-rich middle phase and aqueous and
      isooctane-rich "excess" phases. Both enzymes were rapidly released into the
      aqueous excess phase, with 70% recovery of each in 30 and 60 min for
      microemulsion solutions containing 0.15 and 1.2 M: surfactant, respectively. The
      recovered enzymes retained >90% of their original specific activity.

PMID- 17235489
TI  - Antitumor therapeutic effects of Salmonella typhimurium containing Flt3 Ligand
      expression plasmids in melanoma-bearing mouse.
AB  - An attenuated strain of Salmonella typhimurium has been tested in animals and
      clinically as an anticancer agent due to its in vivo tumor-targeting and
      tumoricidal properties. We exploited a genetically-engineered S. typhimurium
      harboring Flt3 Ligand (Flt3L) expression vectors as a tumoricidal agent to
      enhance its therapeutic efficacy. Flt3L showed tumoricidal effects when expressed
      in tumor cells in vitro. When melanoma-bearing mice were treated locally with
      Salmonella, S. typhimurim with Flt3L expression vectors inhibited tumor growth
      more than Salmonella controls (50% vs. 0% in tumor regression rates). Moreover,
      it prolonged survivals of animals without induction of memory antitumor
      protective responses to a parental tumor re-challenge (50% vs. 0% in survival
      rates). These results suggest that a genetically engineered S. typhimurium with
      Flt3L expression vectors has the potential to be applicable as a safer and more
      effective tumor-targeting and tumoricidal agent.

PMID- 17235488
TI  - Novel detection of Escherichia coli beta-D-glucuronidase activity using a
      microbially-modified glassy carbon electrode and its potential for faecal
      pollution monitoring.
AB  - The electrochemical detection of Escherichia coli beta-D-glucuronidase activity
      as a means of monitoring water pollution by faecal material was investigated
      using separate Moraxella- and Pseudomonas putida-modified glassy carbon
      electrodes. The former was more sensitive and selective. The Moraxella-modified
      biosensor was 100 times more rapid and sensitive than the spectrophotometric
      detection of beta-D-glucuronidase activity. The experimental limit of detection
      of the biosensor was two c.f.u. per 100 ml polluted water sample within 20 min.
      The biosensor gave a linear response to commercial beta-D-glucuronidase
      concentration between 0.2 ng and 2 microg ml(-1). The biosensor detected activity
      of beta-D-glucuronidase from viable but non-culturable (VBNC) cells and can
      therefore serve as a presence or absence device for rapid water quality
      monitoring.

PMID- 17235490
TI  - Multiple sites of retardation of electron transfer in Photosystem II after
      hydrolysis of phosphatidylglycerol.
AB  - Phosphatidylglycerol (PG), containing the unique fatty acid Delta3, trans-16:1
      hexadecenoic acid, is a minor but ubiquitous lipid component of thylakoid
      membranes of chloroplasts and cyanobacteria. We investigated its role in electron
      transfers and structural organization of Photosystem II (PSII) by treating
      Arabidopsis thaliana thylakoids with phospholipase A(2) to decrease the PG
      content. Phospholipase A(2) treatment of thylakoids (a) inhibited electron
      transfer from the primary quinone acceptor Q(A) to the secondary quinone acceptor
      Q(B), (b) retarded electron transfer from the manganese cluster to the redox
      active tyrosine Z, (c) decreased the extent of flash-induced oxidation of
      tyrosine Z and dark-stable tyrosine D in parallel, and (d) inhibited PSII
      reaction centres such that electron flow to silicomolybdate in continuous light
      was inhibited. In addition, phospholipase A(2) treatment of thylakoids caused the
      partial dissociation of (a) PSII supercomplexes into PSII dimers that do not have
      the complete light-harvesting complex of PSII (LHCII); (b) PSII dimers into
      monomers; and (c) trimers of LHCII into monomers. Thus, removal of PG by
      phospholipase A(2) brings about profound structural changes in PSII, leading to
      inhibition/retardation of electron transfer on the donor side, in the reaction
      centre, and on the acceptor side. Our results broaden the simple view of the
      predominant effect being on the Q(B)-binding site.

PMID- 17235491
TI  - The PSII calcium site revisited.
AB  - Oxidation of H2O by photosystem II is a unique redox reaction in that it requires
      Ca2+ as well as Cl- as obligatory activators/cofactors of the reaction, which is
      catalyzed by Mn atoms. The properties of the binding site for Ca2+ in this
      reaction resemble those of other Ca2+ binding proteins, and recent X-ray
      structural data confirm that the metal is in fact ligated at least in part by
      amino acid side chain oxo anions. Removal of Ca2+ blocks water oxidation
      chemistry at an early stage in the cycle of redox reactions that result in O-O
      bond formation, and the intimate involvement of Ca2+ in this reaction that is
      implied by this result is confirmed by an ever-improving set of crystal
      structures of the cyanobacterial enzyme. Here, we revisit the photosystem II Ca2+
      site, in part to discuss the additional information that has appeared since our
      earlier review of this subject (van Gorkom HJ, Yocum CF In: Wydrzynski TJ, Satoh
      K (eds) Photosystem II: the light-driven water:plastoquinone oxidoreductase), and
      also to reexamine earlier data, which lead us to conclude that all S-state
      transitions require Ca2+.

PMID- 17235492
TI  - Hydrogen peroxide-induced chlorophyll a bleaching in the cytochrome b6f complex:
      a simple and effective assay for stability of the complex in detergent solutions.
AB  - The instability of cytochrome b ( 6 ) f complex in detergent solutions is a well
      known problem that has been studied extensively, but without finding a
      satisfactory solution. One of the important reasons can be short of the useful
      method to verify whether the complex suspended in different detergent is in an
      intact state or not. In this article, a simple and effective assay for stability
      of the complex was proposed based on the investigation on the different effects
      of the two detergents, n-octyl-beta-D: -glucopyranoside (OG) and dodecyl-beta-D: 
      maltoside (DDM), on the properties of the complex. DDM stabilizes the complex
      preparation more effectively whereas OG denatures the interactions of the heme
      groups and pigment molecules with the protein environment, leading to the
      bleaching of chlorophyll a induced by addition of hydrogen peroxide. The assay of
      the use of hydrogen peroxide to characterize the complex by studying the
      bleaching of chlorophyll induced by hydrogen peroxide and the peroxidase activity
      of the complex was discussed. This simple method will probably be useful to study
      the stability of the complex.

PMID- 17235494
TI  - Marijuana and tobacco use among young adults in Canada: are they smoking what we
      think they are smoking?
AB  - The authors characterized marijuana smoking among young adult Canadians, examined
      the co-morbidity of tobacco and marijuana use, and identified correlates
      associated with different marijuana use consumption patterns. Data were collected
      from 20,275 individuals as part of the 2004 Canadian Tobacco Use Monitoring
      Survey. Logistic regression models were conducted to examine characteristics
      associated with marijuana use behaviors among young adults (aged 15-24). Rates of
      marijuana use were highest among current smokers and lowest among never smokers.
      Marijuana use was more prevalent among males, young adults living in rural areas,
      and increased with age. Young adults who were still in school were more likely to
      have tried marijuana, although among those who had tried, young adults outside of
      school were more like to be heavy users. Males and those who first tried
      marijuana at an earlier age also reported more frequent marijuana use. These
      findings illustrate remarkably high rates of marijuana use and high co-morbidity
      of tobacco use among young adult Canadians. These findings suggest that future
      research should consider whether the increasing popularity of marijuana use among
      young adults represents a threat to the continuing decline in tobacco use among
      this population.

PMID- 17235493
TI  - Rapid purification of photosystem I chlorophyll-binding proteins by differential
      centrifugation and vertical rotor.
AB  - Photosystem I (PSI), which consists of a core complex and light-harvesting
      complex I (LHCI), is an important multisubunit pigment-protein complex located in
      the photosynthetic membranes of cyanobacteria, algae and plants. In the present
      study, we described a rapid method for isolation and purification of PSI and its
      subfractions. For purification of PSI, crude PSI was first prepared by
      differential centrifugation, which was applicable on a large scale at low cost.
      Then PSI was purified by sucrose gradient ultracentrifugation in a vertical rotor
      to reduce the centrifugation time from more than 20 h when using a swinging
      bucket rotor to only 3 h. Similarly, for subfractionation of PSI into the core
      complex and light-harvesting complex I, sucrose gradient ultracentrifugation in a
      vertical rotor was also used and it took only 4 h to obtain the PSI core, LHCI
      680, and LHCI-730 at the same time. The resulting preparations were characterized
      by sodium dodecyl-sulfate-polyacrylamide gel electrophoresis (SDS-PAGE),
      absorption spectroscopy, and 77 K fluorescence spectroscopy. In addition, their
      pigment composition was analyzed by high-performance liquid chromatography and
      the results showed that each Lhca could bind 1.5-1.6 luteins, 1.0 Violaxanthins,
      and 0.8-1.1 beta-carotenes on average, demonstrating that fewer carotenoids were
      released than with the slower traditional centrifugation. These results showed
      that the rapid isolation procedure, based on differential centrifugation and
      sucrose gradient ultracentrifugation in a vertical rotor, was efficient, and it
      should significantly facilitate preparation and studies of plant PSI. Moreover,
      the vertical rotor, rather than the swinging bucket rotor, may be a good choice
      for isolation of some other proteins.

PMID- 17235495
TI  - How valid is using cancer registries' data to identify acquired immunodeficiency
      syndrome-related non-Hodgkin's lymphoma?
AB  - OBJECTIVE: We sought to determine the accuracy of cancer registry data regarding
      the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)
      status of patients with non-Hodgkin's lymphoma (NHL). METHODS: We used the
      population-based San Diego/Orange County cancer registry to identify 392 patients
      with HIV-related NHL diagnosed 1994-1999. After matching for age, sex, race,
      period of NHL diagnosis, and hospital type, we were able to find 324
      corresponding patients among the remaining 4,863 NHL patients diagnosed 1994-1999
      (who did not have HIV infection according to cancer registry records). We sought
      to review these patients' charts at 41 hospitals with 15 separate institutional
      review boards to determine if the HIV serostatus from the cancer registry was
      correct. We performed a forward conditional multivariate logistic regression to
      determine characteristics associated with a false positive HIV status. RESULTS:
      The false positive rate was 8% while the false negative rate was 3%. The positive
      predictive value was 93% while the negative predictive value was 97%. Compared to
      correctly identified patients, false positives were more likely to be > or =50
      years old, female, and treated with chemotherapy and less likely to be single
      with high grade or extranodal disease. CONCLUSION: Using cancer registry data to
      identify AIDS-related NHL is a valid research practice.

PMID- 17235496
TI  - Lung cancer mortality and body mass index in a Japanese cohort: findings from the
      Japan Collaborative Cohort Study (JACC Study).
AB  - OBJECTIVE: To determine the relationship of body mass index (BMI) and BMI changes
      during adulthood to lung cancer mortality in a large-sized Japanese cohort.
      METHODS: We followed 29,350 men for a maximum of 11 years in the Japan
      Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study), which was
      initiated from 1988 to 1990. Complementary log-log modeling was employed with
      age, smoking status, and family history of lung cancer as covariates.
      Anthropometric measurements used were BMI at baseline, BMI around age 20, and
      adulthood BMI loss defined between the two measurements. Independent effects of
      these three measurements on lung cancer mortality were evaluated by applying the
      method of generalized estimation equations to the model for adjustment of intra
      individual correlation. RESULTS: Never smokers showed that high BMI both at
      baseline and around age 20 significantly predict lung cancer mortality (P <
      0.05). Adulthood BMI loss significantly (P < 0.05) elevated the risk for lung
      cancer mortality among current smokers, implying their enhanced vulnerability to
      lung cancer risk among smokers. CONCLUSIONS: The risk for lung cancer mortality
      is elevated by a mechanism related to smoking-induced weight loss during
      adulthood.

PMID- 17235498
TI  - Search for effective natural enemies of Tetranychus evansi in south and southeast
      Brazil.
AB  - Tetranychus evansi Baker & Pritchard is an important pest of Solanaceae in
      several countries. Introduced accidentally to Africa, it presently occurs in many
      countries of that continent. In some of them, it is considered a key pest. The
      suspected area of origin of this mite is South America. The objective of the
      present study was to identify phytoseiid mites on solanaceous plants in
      association with T. evansi in south and southeast Brazil for introduction in the
      African continent for use in a classic biological control program. Almost 1,400
      predatory mites of the family Phytoseiidae were collected, on 22 solanaceous
      species. The Amblyseiinae were the most diverse group in this study. Twenty-three
      of the species found belong to this subfamily, while only three belong to the
      Typhlodrominae and two to the Phytoseiinae. The most abundant and most frequent
      phytoseiid species were Phytoseius guianensis De Leon and Galendromus annectens
      (De Leon) of the Phytoseiinae and Typhlodrominae, respectively. The most frequent
      and abundant species of Amblyseiinae was Neoseiulus tunus (De Leon). Phytoseius
      guianensis and N. tunus were never found in association with T. evansi and G.
      annectens was found only once in association with it. Two factors suggested
      Phytoseiulus longipes Evans as the most promising predator found in this study.
      It could walk very well on tomato leaves infested by T. evansi, without being
      hampered by the profuse webbing produced by the prey and by the trichomes. In
      addition, several specimens of both sexes including eggs and nymphs of the
      predator were found associated with T. evansi on three different plant species
      and in two different periods of the year, when T. evansi was the only arthropod
      present on the leaves.

PMID- 17235497
TI  - J-Spectroscopy in the presence of residual dipolar couplings: determination of
      one-bond coupling constants and scalable resolution.
AB  - The access to weak alignment media has fuelled the development of methods for
      efficiently and accurately measuring residual dipolar couplings (RDCs) in NMR
      spectroscopy. Among the wealth of approaches for determining one-bond scalar and
      RDC constants only J-modulated and J-evolved techniques retain maximum resolution
      in the presence of differential relaxation. In this article, a number of J
      evolved experiments are examined with respect to the achievable minimum linewidth
      in the J-dimension, using the peptide PA4 and the 80-amino-acid-protein Saposin C
      as model systems. With the JE-N-BIRDd,X-HSQC experiment, the average full-width
      at half height could be reduced to approximately 5 Hz for the protein, which
      allows the additional resolution of otherwise unresolved peaks by the active
      (J+D)-coupling. Since RDCs generally can be scaled by the choice of alignment
      medium and alignment strength, the technique introduced here provides an
      effective resort in cases when chemical shift differences alone are insufficient
      for discriminating signals. In favorable cases even secondary structure elements
      can be distinguished.

PMID- 17235499
TI  - Development of an electronic tongue based on a PEDOT-modified voltammetric
      sensor.
AB  - Three different electrodes were tested for use as nonspecific amperometric
      sensors for blind analysis on real matrices, namely different fruit juices from
      different fruits or different brands. The first two electrodes were traditional
      Pt and Au electrodes, while the third one was modified with poly(3,4
      ethylenedioxythiophene) conducting polymer. The sensors were tested separately,
      tested coupled to each other, and also tested together. The responses of the
      electrode system(s) were first screened via PCA and then their discriminant
      capabilities were quantified in terms of the sensitivities and specificities of
      their corresponding PLS-DA multivariate classification models. Particular
      attention was paid to analyzing the evolution of the response over subsequent
      potential sweeps. The modified electrode demonstrated the most discriminating
      ability, and it was the only system capable of satisfactorily performing the most
      complex task attempted during the analysis: discriminating between juices from
      the same fruit but from different brands. Moreover, the electrode "cleaning"
      procedure required between two subsequent potential sweeps was much simpler for
      the modified electrode than for the others. This electrode system was therefore
      shown to be a good candidate for use as an informative element in an electronic
      tongue applied to the analysis of other food matrices.

PMID- 17235500
TI  - Critical evaluation of the application of photochemical vapor generation in
      analytical atomic spectrometry.
AB  - Chemical vapor generation (CVG) is a widely adopted sample introduction method
      for analytical atomic spectrometry. Nonvolatile precursors (usually ionic,
      metallic or organometallic species) can be transferred from the condensed phase
      to the gas phase, yielding the advantages of efficient matrix separation, high
      analyte transport efficiency, high selectivity, simple instrumentation, and ease
      of automation. Hydride generation enjoys the greatest popularity as a consequence
      of its ease of implementation, fast reaction and high yield; but photo-CVG, a
      newly emerging research field in analytical chemistry, may provide a powerful
      alternative to conventional CVG due to its simplicity, versatility and cost
      effectiveness. Although photocatalytic pre-reduction has been used for a number
      of years, the most attractive aspect of this newly emerging area is the direct
      generation of volatile species using photochemical reactions. Recent studies
      undertaken with flow through and batch reactors employing low molecular weight
      organic acids as photochemical agents are highlighted in this study for such
      systems as mercury and selenium, as well as reaction mechanisms considered for
      these processes. Discussion is focused on recent advances in photo-CVG, which we
      believe will become the subject of intensive future research initiatives.

PMID- 17235501
TI  - Efficacy of the BioXtra dry mouth care system in the treatment of radiotherapy
      induced xerostomia.
AB  - INTRODUCTION: Xerostomia is a common complication of radiotherapy for head and
      neck cancer. Symptomatic treatment consists of stringent oral hygiene to prevent
      oral infections and saliva substitutes to increase comfort. The aim of the study
      was to evaluate the clinical effectiveness of the BioXtra (BX) dry mouth care
      system. MATERIALS AND METHODS: A xerostomia questionnaire consisting of 3 parts
      (xerostomia symptom score, quality of life (QoL) survey and visual analogue scale
      (VAS)) was completed by 34 patients suffering from radiation-induced xerostomia,
      before and after 4 weeks of treatment with the BioXtra moisturizing gel,
      toothpaste and mouthwash. RESULTS: The BioXtra products significantly diminished
      the most common symptoms of xerostomia. Mean VAS score at the start of treatment
      was 59.8. After treatment, this decreased to 36.4 (p < 0.001). Twenty-six
      patients (77%) responded to treatment, 11 of these patients (32%) reported a
      major improvement. Quality of life significantly improved under treatment: mean
      QoL score at the start was 59.4; this increased to 70.5 (p < 0.001). None of the
      34 patients reported any adverse effects and all but 1 patient found the BX dry
      mouth care system easy to use. CONCLUSIONS: The results of this study suggest
      that the BioXtra dry mouth care system is effective in reducing the symptoms of
      radiation-induced xerostomia and improving the quality of life of xerostomia
      patients, even if a proportion of the benefit is due to a placebo effect.
      However, further research is necessary to evaluate the efficacy of BioXtra on
      oral health.

PMID- 17235502
TI  - A prospective study on C-reactive protein as a prognostic factor for survival
      time of terminally ill cancer patients.
AB  - GOALS OF WORK: C-reactive protein (CRP) has been investigated as a predictor of
      life expectancy in terminal cancer in one previous study. However, the other
      variables such as patient's symptom or physical examination findings were not
      considered. The aim of this study is to prove serum CRP level as a predictor of
      survival time, considering patient's symptoms, physical examination findings, and
      various serological variables in terminally ill cancer patients with a
      prospective cohort design. PATIENTS AND METHODS: Forty-four terminally ill cancer
      patients were divided into two groups by serum CRP levels and followed up until
      death. We adjusted the influence of some clinical and laboratory variables on
      survival by use of Cox's proportional hazard model. Using the stepwise variable
      selection method, we found the final model. For 19 patients, CRP levels at 2
      weeks and a week before death were compared by Wilcoxon signed ranks test. MAIN
      RESULTS: All 44 study subjects died during the study period, and the median
      survival time was 17 days. Survival time of the elevated CRP group (> or =2.2
      mg/dl) was found to be significantly shorter than the lower CRP group in
      univariate analysis (hazard rate = 3.221, P = 0.001). In multivariate analysis,
      elevated CRP level (> or =2.2 mg/dl) was selected as one of the unfavorable
      indicators regarding survival. Dyspnea and hyperbilirubinemia were also found
      significant predictors of shorter life expectancy in the final model. Serum CRP
      levels were significantly increased between the first and the second week before
      death. CONCLUSIONS: Our results showed that serum CRP level can be a useful
      indicator predictive of survival time of terminally ill cancer patients.

PMID- 17235503
TI  - Patients' needs assessment in cancer care: a review of assessment tools.
AB  - BACKGROUND: The assessment of patients' needs for care is a critical step in
      achieving patient-centred cancer care. Tools can be used to assess needs and
      inform care planning. This review discusses the importance of systematic
      assessment of needs in routine care and the contribution tools can make to this
      process. METHOD: A rapid appraisal was undertaken to identify currently available
      tools for patient assessment in cancer care through searches conducted with
      Medline and CINHAL databases. It focused on tools for the systematic assessment
      of individual patients' needs for help, care or support, to be used for clinical
      purposes-not for research or other purposes. Tools that focused on a single
      domain of care such as psychosocial needs were excluded, as were studies of
      patient satisfaction. A wide list of search terms was used, with references
      stored and managed using bibliographic software. RESULTS: In all, 1,803 papers
      were identified from the initial search, with 91 papers found to be relevant;
      although 36 tools were identified, only 15 tools were found to fit our criteria.
      These were appraised for their validity, reliability, responsiveness to change
      and feasibility, including acceptability to patients. The process of their
      development and psychometric properties were reasonably well documented, but data
      on how feasible they were to use in practice was scarce. Each tool met some but
      not all the widely accepted criteria for validity, reliability, responsiveness
      and burden. None were found to be complete for all dimensions of needs
      assessment. Most have not been sufficiently well tested for use in routine care.
      CONCLUSION: There is a need to continue to develop and test tools that have the
      attributes necessary for effective practice and to research their effects on the
      quality of supportive cancer care.

PMID- 17235504
TI  - Pegfilgrastim as hematopoietic support for dose-dense chemoimmunotherapy with R
      CHOP-14 as first-line therapy in elderly patients with diffuse large B cell
      lymphoma.
AB  - GOALS OF WORK: Recently, 6 cycles of R-CHOP-14 have been recommended as the
      reference standard regimen for the treatment of elderly patients with diffuse
      large B-cell lymphoma (DLBCL). Pegfilgrastim has been shown to facilitate dose
      dense chemotherapy schedules with a single administration per chemotherapy cycle.
      The aims of this study were to evaluate the use of pegfilgrastim in combination
      with the R-CHOP-14 regimen in a homogenous group of previously untreated elderly
      patients with DLBCL and to assess the pharmacokinetics of pegfilgrastim within
      this patient population. MATERIALS AND METHODS: Ten patients with DLBCL between
      60 and 80 years of age received a single subcutaneous injection of 6 mg
      pegfilgrastim 24 h after administration of R-CHOP chemoimmunotherapy, which was
      repeated for 6 to 8 cycles in two-weekly intervals. A total of 348 blood samples
      were collected. Pegfilgrastim plasma levels and absolute neutrophil counts were
      measured every other day during the first treatment cycle and twice weekly during
      all consecutive cycles. MAIN RESULTS: Sixty-three of 72 cycles (87.5%) could be
      delivered on time and at the planned dose. Median absolute neutrophil nadir was
      0.32 g/l on day 9. Grade 3/4 granulocytopenia occurred in all patients. Febrile
      neutropenia occurred in two patients. Plasma levels of pegfilgrastim remained
      elevated during the neutropenic phase. At the start of hematologic recovery,
      plasma concentrations of pegfilgrastim decreased rapidly to baseline levels.
      Median pegfilgrastim trough plasma level was 0.43 ng/ml on the day preceding the
      next application. CONCLUSIONS: A single fixed dose of 6 mg of pegfilgrastim given
      once per cycle of R-CHOP-14 is effective in supporting neutrophil recovery to
      allow two-weekly drug administration in previously untreated elderly patients
      with DLBCL. However, close monitoring for infectious complications is mandatory
      in this patient population.

PMID- 17235505
TI  - Colitis cystica profunda associated with rectal prolapse: report of a case.

PMID- 17235507
TI  - Ileus due colon endometriosis and the role of MRI scan.

PMID- 17235508
TI  - Reproducibility of physiological track-and-trigger warning systems for
      identifying at-risk patients on the ward.
AB  - OBJECTIVE: Physiological track-and-trigger warning systems are used to identify
      patients on acute wards at risk of deterioration, as early as possible. The
      objective of this study was to assess the inter-rater and intra-rater reliability
      of the physiological measurements, aggregate scores and triggering events of
      three such systems. DESIGN: Prospective cohort study. SETTING: General medical
      and surgical wards in one non-university acute hospital. PATIENTS AND
      PARTICIPANTS: Unselected ward patients: 114 patients in the inter-rater study and
      45 patients in the intra-rater study were examined by four raters. MEASUREMENTS
      AND RESULTS: Physiological observations obtained at the bedside were evaluated
      using three systems: the medical emergency team call-out criteria (MET); the
      modified early warning score (MEWS); and the assessment score of sick-patient
      identification and step-up in treatment (ASSIST). Inter-rater and intra-rater
      reliability were assessed by intra-class correlation coefficients, kappa
      statistics and percentage agreement. There was fair to moderate agreement on most
      physiological parameters, and fair agreement on the scores, but better levels of
      agreement on triggers. Reliability was partially a function of simplicity: MET
      achieved a higher percentage of agreement than ASSIST, and ASSIST higher than
      MEWS. Intra-rater reliability was better then inter-rater reliability. Using
      corrected calculations improved the level of inter-rater agreement but not intra
      rater agreement. CONCLUSION: There was significant variation in the
      reproducibility of different track-and-trigger warning systems. The systems
      examined showed better levels of agreement on triggers than on aggregate scores.
      Simpler systems had better reliability. Inter-rater agreement might improve by
      using electronic calculations of scores.

PMID- 17235506
TI  - Survival rates for stage II colon cancer patients treated with or without
      chemotherapy in a population-based setting.
AB  - BACKGROUND AND AIMS: There is considerable uncertainty as to whether adjuvant 5
      fluorouracil-based chemotherapy provides survival benefit for colon cancer
      patients with stage II disease. Consequently, the current rates of chemotherapy
      use for this disease are low despite 5-year survival rates of only 70-80%. The
      aim of the present study is to compare the survival rate of stage II colon cancer
      patients treated by surgery alone with that of patients also treated by
      chemotherapy. PATIENTS AND METHODS: A population-based observational study was
      conducted on the survival of stage II colon cancer patients (n = 812) diagnosed
      in Western Australia from 1993 to 2003. The study was restricted to patients aged
      < or =75 years, of whom 18% (n = 142) were treated with chemotherapy. Only 0.9%
      of patients older than 75 years received chemotherapy. RESULTS: Patients who
      received chemotherapy were significantly younger (mean age 6 years) than those
      treated by surgery alone (65 years, P < 0.001), and their tumors were more often
      positive for vascular invasion (P = 0.007). Multivariate analysis that included
      all prognostic factors revealed adjuvant chemotherapy was associated with
      improved survival (HR = 0.62, 95% CI [0.39-0.98], P = 0.043), with women gaining
      more benefit (HR = 0.48, 95% CI [0.20-1.22], P = 0.09) than men (HR = 0.94, 95%
      CI [0.54-1.64], P = 0.8). CONCLUSIONS: In view of the apparent survival benefit
      from chemotherapy for stage II colon cancer, the present study raises concerns
      about the current low rates of adjuvant treatment for this disease in the
      community, particularly for female patients.

PMID- 17235510
TI  - Effect of ornithine alpha-ketoglutarate on glutamine pools in burn injury:
      evidence of component interaction.
AB  - BACKGROUND: Ornithine alpha-ketoglutarate (OKG) has proved to be efficient in
      restoring glutamine (Gln) pools which are strongly depleted in hypercatabolic
      patients. Since its two components, alpha-ketoglutarate (alphaKG) and ornithine
      (Orn), give rise to glutamate (Glu), they are both considered as Gln precursors.
      The aim of this study was to assess the relative contributions of Orn and alphaKG
      to Gln generation in a rat model of burn injury. METHODS: Forty-eight young
      Wistar rats were scalded to give a 20% burn surface area. They were fasted for 24
      h and then refed by enteral nutrition for 48 h by gavages with Osmolite (Abbott
      Ross, 210 kcal/kg day(-1), 1.18 N/kg day(-1)) supplemented with either 5 g OKG/kg
      day(-1) (B-OKG), Orn (isomolar to OKG; B-Orn), alphaKG (isomolar to OKG; B-KG) or
      glycine (as an isonitrogenous control; B-Gly). Rats in the B-KG group also
      received glycine to make all the groups isonitrogenous. Amino acid concentrations
      were determined in plasma, muscles, jejunal mucosa and liver. RESULTS: The alpha
      KG-enriched diet had no effect on plasma Glu content or plasma and muscle Gln
      content compared with the burn-injured controls. The Orn-enriched diet
      significantly increased (p<0.01) muscle Glu and Gln contents but not plasma Gln
      content. In OKG-treated animals, plasma Gln as well as muscle Glu and Gln were
      significantly higher than in the control (p<0.01), alpha-KG-treated (p< 0.01) and
      Orn-treated (p<0.05 for muscle Gln and p<0.01 for plasma Gln) animals.
      CONCLUSION: OKG was more efficient than Orn or alphaKG alone in restoring Gln
      pools in plasma and muscle, which is evidence of metabolic interaction between
      the two components of this molecule.

PMID- 17235509
TI  - Ionic dialysance: a new valid parameter for quantification of dialysis efficiency
      in acute renal failure?
AB  - OBJECTIVE: Several studies have reported a close relationship between an
      increased dose of dialysis and survival in patients treated for acute renal
      failure. Unfortunately, the quantification of dialysis in critically ill patients
      based on the urea nitrogen formula Kt/V is not applicable. Ionic dialysance is a
      new parameter calculated in real time from the dialysate conductivity and
      correlated with the effective urea clearance in chronic hemodialysis patients.
      The aim of our study was to evaluate ionic dialysance in the quantification of
      dialysis in critically ill patients with acute renal failure. DESIGN: Prospective
      open-label study. SETTING: An 18-bed medical intensive care unit. PATIENTS:
      Thirty-one patients with multiple organ dysfunction syndrome and acute renal
      failure requiring intermittent hemodialysis were included. MEASUREMENTS: Using
      the first dialysis session of each patient, we compared the delivered dose of
      dialysis based on ionic dialysance measurement (Kt(ID)) with the well-accepted
      gold standard method based on fractional dialysate sampling (Kt(dialysate)). The
      data were analyzed using linear regression and Bland-Altman analysis. RESULTS:
      Thirty-one intermittent hemodialysis sessions were performed in 31 critically ill
      patients (mean age 58+/-12 years, SAPS II score 56+/-10). We found a close
      correlation between Kt(dialysate) and Kt(ID) (Kt(dialysate) = 36.3+/-11.4 l;
      Kt(ID)=38.4+/-11.8; r=0.96) with excellent limits of agreement (-2.2 l; 6.4 l).
      CONCLUSION: The feasibility of dialysis quantification based on ionic dialysance
      in the critically ill patient is good. This method is a simple and accurate tool
      for the determination of dialysis dose in critically ill patients.

PMID- 17235511
TI  - Sedation assessment tool, sedation-algorithm, choice of sedation drugs: intricate
      concepts of an emergent clinical practice.

PMID- 17235512
TI  - Infectious complications of percutaneous central venous catheterization in
      pediatric patients: a Spanish multicenter study.
AB  - OBJECTIVE: Analysis of infectious complications and risk factors in percutaneous
      central venous catheters. DESIGN: One-year observational, prospective,
      multicenter study (1998-1999). SETTING: Twenty Spanish pediatric intensive care
      units. PATIENTS: Eight hundred thirty-two children aged 0-14 years. INTERVENTION:
      None. MEASUREMENTS AND MAIN RESULTS: One thousand ninety-two catheters were
      analyzed. Seventy-four (6.81%) catheter-related bloodstream infections (CRBSI)
      were found. The CRBSI rate was 6.4 per 1,000 CVC days (95% CI 5.0-8.0). Risk
      factors for CRBSI were weight under 8 kg (p < 0.001), cardiac failure (RR 2.69;
      95% CI 1.95-4.38; p < 0.001), cancer (RR 1.66; 95% CI 0.97-2.78; p=0.05),
      silicone catheters (RR 2.82; 95% CI 1.49-5.35; p = 0.006), guidewire exchange
      catheterization (p=0.002), obstructed catheters (RR 2.67; 95% CI 1.63-4.39;
      p<0.001), and more than 12 days' indwelling time (RR 5.9; 95% CI 3.63-9.41;
      p<0.001). Multivariate Cox regression identified lower patient weight (HR 2.4;
      95% CI 1.11-5.19; p=0.002), guidewire exchange catheterization (HR 2.2; 95% CI
      1.07-4.54; p=0.049) and more than 12 days' indwelling time (HR 1.97; 95% CI 0.89
      4.36; p=0.089) as significant independent predictors of CRBSI. Factors which
      protected against infection were the use of povidone-iodine on hubs (HR 0.42; 95%
      CI 0.19-0.96; p=0.025) and porous versus impermeable dressing (HR 0.41; 95% CI
      0.23-0.74; p=0.004). Two children (0.24%) died from endocarditis following
      catheter-related sepsis due to Stenotrophomonas maltophilia in one case and P.
      aeruginosa in the other. CONCLUSIONS: Catheter-related sepsis is associated with
      lower patient weight and more than 12 days' indwelling time, but not with the
      insertion site. Cleaning hubs with povidone-iodine protects from infection.

PMID- 17235513
TI  - Vascular erosion by central venous catheters used for total parenteral nutrition.
AB  - OBJECTIVE: To establish the incidence of central venous catheter erosion in a
      patient cohort receiving total parenteral nutrition and to examine risk factors
      and complications of vascular erosion. DESIGN AND SETTING: Review of
      prospectively collected intravenous nutrition service audit records in a tertiary
      university hospital. RESULTS: Records of 1,499 patients (2,992 catheters) were
      studied over the 14 year period 1991-2005. Fisher's exact test was used to
      determine statistical significance. Five erosions occurred, representing an
      incidence of 0.17% per catheter or 0.28 per 1,000 catheter days. One of the five
      patients died from ensuing complications. Mean time to onset of symptoms was 3.6
      days following catheter insertion. Symptoms/signs included dyspnoea (n=5), chest
      pain (n=2) and pleural effusion (n=5). Diagnosis was delayed by a mean of 1.6
      days. Three erosions occurred in left subclavian catheters (n=583); two in left
      internal jugular catheters (n=453). None occurred in right-sided catheters
      (n=1956). The relative risk of erosion occurring in left-sided catheters compared
      to right was 2.9 (95% CI 2.76-3.00; p=0.009). There was no statistically
      significantly greater risk of vascular erosion in subclavian than internal
      jugular catheters (relative risk 0.9; p=1.0). Older age was a statistically
      significant risk factor (p=0.009); female sex was not (p=0.18). CONCLUSION: In
      patients receiving total parenteral nutrition via central venous catheters,
      erosion has an incidence per catheter of 0.17% and is more likely to occur in
      left-sided catheters and elderly patients.

PMID- 17235514
TI  - PIK3CA alterations in primary (de novo) and secondary glioblastomas.
AB  - We assessed alterations in the EGFR/PTEN/PI3K pathway in 107 primary (de novo)
      glioblastomas and 32 secondary glioblastomas that progressed from low-grade or
      anaplastic astrocytomas. SSCP followed by DNA sequencing in exons 9 and 20 of the
      PIK3CA gene revealed missense mutations in 5/107 (5%) primary and 1/32 (3%)
      secondary glioblastomas. Quantitative real-time PCR showed PIK3CA amplification
      (>3 copy numbers) in 14/107 (13%) primary and 3/32 (9%) secondary glioblastomas.
      Only one glioblastoma showed both PIK3CA mutation and amplification. Taken
      together with previously published data on EGFR amplification and PTEN mutations,
      at least one alteration in the EGFR, PTEN, or PIK3CA genes was detected in 63% of
      primary glioblastomas, which was significantly more frequent than in secondary
      glioblastomas (31%; P < 0.001). Furthermore, this signaling pathway was altered
      by either PTEN mutations or PIK3CA amplification in 10 of 12 (83%) malignant
      glioma cell lines analyzed. These results suggest that the EGFR/PTEN/PI3K pathway
      is frequently altered in glioblastomas and is a promising target for therapy, in
      particular for primary glioblastomas.

PMID- 17235515
TI  - Decreased GAD67 mRNA levels in cerebellar Purkinje cells in autism:
      pathophysiological implications.
AB  - The recent identification of decreased protein levels of glutamate decarboxylase
      (GAD) 65 and 67 isoforms in the autistic cerebellar tissue raises the possibility
      that abnormal regulation of GABA production in individual neurons may contribute
      to the clinical features of autism. Reductions in Purkinje cell number have been
      widely reported in autism. It is not known whether the GAD changes also occur in
      Purkinje cells at the level of transcription. Using a novel approach, the present
      study quantified GAD67 mRNA, the most abundant isoform in Purkinje cells, using
      in situ hybridization in adult autistic and control cases. The results indicate
      that GAD67 mRNA level was reduced by 40% in the autistic group (P < 0.0001; two
      tailed t test), suggesting that reduced Purkinje cell GABA input to the
      cerebellar nuclei potentially disrupts cerebellar output to higher association
      cortices affecting motor and/or cognitive function. These findings may also
      contribute to the understanding of previous reports of alterations in the
      GABAergic system in limbic and cerebro-cortical areas contributing to a more
      widespread pathophysiology in autistic brains.

PMID- 17235517
TI  - Genetic relationship between Murcia Region (SE Spain) and other populations in
      the Iberian Peninsula and Mediterranean area with respect to HFE gene mutations
      distribution.

PMID- 17235518
TI  - Hyperleukocytosis in patients with leukemic follicular lymphoma.

PMID- 17235516
TI  - Cold-active enzymes studied by comparative molecular dynamics simulation.
AB  - Enzymes from cold-adapted species are significantly more active at low
      temperatures, even those close to zero Celsius, but the rationale of this
      adaptation is complex and relatively poorly understood. It is commonly stated
      that there is a relationship between the flexibility of an enzyme and its
      catalytic activity at low temperature. This paper gives the results of a study
      using molecular dynamics simulations performed for five pairs of enzymes, each
      pair comprising a cold-active enzyme plus its mesophilic or thermophilic
      counterpart. The enzyme pairs included alpha-amylase, citrate synthase, malate
      dehydrogenase, alkaline protease and xylanase. Numerous sites with elevated
      flexibility were observed in all enzymes; however, differences in flexibilities
      were not striking. Nevertheless, amino acid residues common in both enzymes of a
      pair (not present in insertions of a structure alignment) are generally more
      flexible in the cold-active enzymes. The further application of principle
      component analysis to the protein dynamics revealed that there are differences in
      the rate and/or extent of opening and closing of the active sites. The results
      indicate that protein dynamics play an important role in catalytic processes
      where structural rearrangements, such as those required for active site access by
      substrate, are involved. They also support the notion that cold adaptation may
      have evolved by selective changes in regions of enzyme structure rather than in
      global change to the whole protein.

PMID- 17235519
TI  - InterB multigenic family, a gene repertoire associated with subterminal
      chromosome regions of Encephalitozoon cuniculi and conserved in several human
      infecting microsporidian species.
AB  - Microsporidia are fungi-related obligate intracellular parasites that infect
      numerous animals, including man. Encephalitozoon cuniculi harbours a very small
      genome (2.9 Mbp) with about 2,000 coding sequences (CDSs). Most repeated CDSs are
      of unknown function and are distributed in subterminal regions that mark the
      transitions between subtelomeric rDNA units and chromosome cores. A potential
      multigenic family (interB) encoding proteins within a size range of 579-641 aa
      was investigated by PCR and RT-PCR. Thirty members were finally assigned to the
      E. cuniculi interB family and a predominant interB transcript was found to
      originate from a newly identified gene on chromosome III. Microsporidian species
      from eight different genera infecting insects, fishes or mammals, were tested for
      a possible intra-phylum conservation of interB genes. Only representatives of the
      Encephalitozoon, Vittaforma and Brachiola genera, differing in host range but all
      able to invade humans, were positive. Molecular karyotyping of Brachiola algerae
      showed a complex set of chromosome bands, providing a haploid genome size
      estimate of 15-20 Mbp. In spite of this large difference in genome complexity, B.
      algerae and E. cuniculi shared some similar interB gene copies and a common
      location of interB genes in near-rDNA subterminal regions.

PMID- 17235520
TI  - Implementing anti-retroviral triple therapy to prevent HIV mother-to-child
      transmission: a public health approach in resource-limited settings.

PMID- 17235521
TI  - Booster vaccination and 1-year follow-up of 4-8-year-old children with a reduced
      antigen-content dTpa-IPV vaccine.
AB  - Reduced-antigen-content pertussis vaccines designed initially for booster
      vaccination of adolescents and adults can also be used to vaccinate pre-school
      age children. Combination vaccines, which reduce the number of administered
      injections, combine multiple antigens including inactivated poliovirus (IPV),
      which is recommended in this age group in some countries. This randomised,
      controlled study compared a combined diphtheria-tetanus-acellular pertussis
      inactivated polio-containing booster vaccine, dTpa-IPV (Boostrix Polio, n=822),
      to separately administered dTpa (Boostrix) and IPV (IPV Merieux, n=136) in 4-8
      year-old children who had previously received four doses of DTPa. Additional
      serological assessment was performed 1 year after the booster dose. One month
      after vaccination, seroprotection/vaccine response rates were similar for both
      groups. At least 99.9% of the subjects had protective antibodies against
      diphtheria, tetanus and polio, and at least 90.1% had a vaccine response to
      pertussis antigens after dTpa-IPV. Reactogenicity of dTpa-IPV was comparable to
      dTpa + IPV. Fever and grade 3 loss of appetite occurred more commonly after dTpa
      IPV, whereas swelling and grade 3 pain occurred more frequently after separately
      administered dTpa + IPV (P<0.05 for all). However, 95% CIs overlapped in all
      cases. Large swelling reactions after dTpa-IPV occurred less commonly than have
      been reported after a fifth dose of DTPa. One year after the booster, 98.6% of
      the subjects tested continued to have protective antibodies against diphtheria,
      tetanus and polio, and at least 81.2% were seropositive for pertussis components.
      The reduced-antigen-content dTpa-IPV vaccine was immunogenic, well tolerated and
      safe in pre-school age children. It provides immunity against four diseases in a
      single injection, with the potential reactogenicity benefit of a reduced-antigen
      dose.

PMID- 17235522
TI  - Comment on: Distiller LA, Joffe BI (2006) From the coalface: does glargine
      insulin improve hypoglycaemic episodes, glycaemic control or affect body mass in
      type 1 diabetic subjects who are attending a 'routine' diabetes clinic?
      Diabetologia 49:2793-2794.

PMID- 17235523
TI  - The dilemma of self-monitoring of blood glucose.

PMID- 17235524
TI  - Expression of the gene encoding the high-Km glucose transporter 2 by the early
      postimplantation mouse embryo is essential for neural tube defects associated
      with diabetic embryopathy.
AB  - AIMS/HYPOTHESIS: Excess glucose transport to embryos during diabetic pregnancy
      causes congenital malformations. The early postimplantation embryo expresses the
      gene encoding the high-Km GLUT2 (also known as SLC2A2) glucose transporter. The
      hypothesis tested here is that high-Km glucose transport by GLUT2 causes
      malformations resulting from maternal hyperglycaemia during diabetic pregnancy.
      MATERIALS AND METHODS: Glut2 mRNA was assayed by RT-PCR. The Km of embryo glucose
      transport was determined by measuring 0.5-20 mmol/l 2-deoxy[3H]glucose transport.
      To test whether the GLUT2 transporter is required for neural tube defects
      resulting from maternal hyperglycaemia, Glut2+/- mice were crossed and transient
      hyperglycaemia was induced by glucose injection on day 7.5 of pregnancy. Embryos
      were recovered on day 10.5, and the incidence of neural tube defects in wild
      type, Glut2+/- and Glut2-/- embryos was scored. RESULTS: Early postimplantation
      embryos expressed Glut2, and expression was unaffected by maternal diabetes.
      Moreover, glucose transport by these embryos showed Michaelis-Menten kinetics of
      16.19 mmol/l, consistent with transport mediated by GLUT2. In pregnancies made
      hyperglycaemic on day 7.5, neural tube defects were significantly increased in
      wild-type embryos, but Glut2+/- embryos were partially protected from neural tube
      defects, and Glut2-/- embryos were completely protected from these defects. The
      frequency of occurrence of wild-type, Glut2+/- and Glut2-/- embryos suggests that
      the presence of Glut2 alleles confers a survival advantage in embryos before day
      10.5. CONCLUSIONS/INTERPRETATIONS: High-Km glucose transport by the GLUT2 glucose
      transporter during organogenesis is responsible for the embryopathic effects of
      maternal diabetes.

PMID- 17235525
TI  - Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy--a
      nationwide 5-year-study in Japan.
AB  - AIMS/HYPOTHESIS: The aim of the present study was to assess the development of
      microangiopathy in patients with fulminant type 1 diabetes, a novel subtype of
      type 1B diabetes. MATERIALS AND METHODS: In a nationwide survey, we followed 41
      patients with fulminant type 1 diabetes and 76 age- and sex-matched patients with
      type 1A diabetes for 5 years. The following data were recorded every 12 months
      after the onset of diabetes: seven-point blood glucose concentrations, HbA1c
      level, urinary albumin excretion, serum C-peptide level, blood pressure, daily
      dosages of insulin, frequency of severe hypoglycaemic episodes, and neurological
      and fundoscopic examination. RESULTS: The 5-year cumulative incidence of
      microangiopathy was 24.4% in fulminant type 1 diabetes and 2.6% in type 1A
      diabetes. In longitudinal studies using the Kaplan-Meier method, the cumulative
      incidence of each form of microangiopathy was significantly higher in fulminant
      type 1 diabetes than in type 1A diabetes; retinopathy was 9.8% vs 0% (p=0.014),
      nephropathy 12.2% vs 2.6% (p=0.015) and neuropathy 12.2% vs 1.3% (p=0.010),
      respectively. Mean HbA1c levels were similar in the fulminant and type 1A
      diabetes groups during the follow-up periods. However, the mean M-value, mean
      insulin dosages and the frequency of severe hypoglycaemic episodes were
      significantly higher, and the mean postprandial C-peptide level was significantly
      lower in the fulminant type 1 diabetes group. CONCLUSIONS/INTERPRETATION: These
      data suggest that patients with fulminant type 1 diabetes are a high-risk
      subgroup for diabetic microangiopathy associated with the lack of endogenous
      insulin secretion from the onset of diabetes.

PMID- 17235526
TI  - C-peptide is a bioactive peptide.

PMID- 17235528
TI  - PET/CT in paediatrics: it is time to increase its use!

PMID- 17235527
TI  - Single nucleotide polymorphisms in the neuropeptide Y2 receptor (NPY2R) gene and
      association with severe obesity in French white subjects.
AB  - AIMS/HYPOTHESIS: Genetic variants of genes for peptide YY (PYY), neuropeptide Y2
      receptor (NPY2R) and pancreatic polypeptide (PPY) were investigated for
      association with severe obesity. SUBJECTS AND METHODS: The initial screening of
      the genes for variants was performed by sequencing in a group of severely obese
      subjects (n=161). Case-control analysis of the common variants was then carried
      out in 557 severely obese adults, 515 severely obese children and 1,163 non
      obese/non-diabetic control subjects. Rare variants were genotyped in 700 obese
      children and the non-obese/non-diabetic control subjects (n=1,163). RESULTS:
      Significant association was found for a 5' variant (rs6857715) in the NPY2R gene
      with both severe adult obesity (p=0.002) and childhood obesity (p=0.02). This
      significant association was further supported by a pooled allelic analysis of all
      obese cases (adults and children, n=928) vs the control subjects (n=938)
      (p=0.0004, odds ratio=1.3, 95% CI 1.1-1.5). Quantitative trait analysis of BMI
      and WHR was performed and significant association was observed for SNP rs1047214
      in NPY2R with an increase in WHR in the severely obese children (co-dominant
      model p=0.005, recessive model p=0.001). Association was also observed for an
      intron 3 variant (rs162430) in the PYY gene with childhood obesity (p=0.04). No
      significant associations were observed for PPY variants. Only one rare variant in
      the NPY2R gene (C-5641T) was not found in lean individuals and this was found to
      co-segregate with obesity in one family. CONCLUSIONS/INTERPRETATION: These
      results provide evidence of association for NPY2R and PYY gene variants with
      obesity and none for PPY variants. A rare variant of the NPY2R gene showed
      evidence of co-segregation with obesity and its contribution to obesity should be
      investigated further.

PMID- 17235529
TI  - Myocardial perfusion imaging with a novel SPECT/CT system: all that glitters is
      not gold.

PMID- 17235530
TI  - Contribution of SLN investigation with 99mTc-nanocolloid in clinical staging of
      thyroid cancer: technical feasibility.
AB  - PURPOSE: It is a matter of controversy whether prophylactic lymph node dissection
      improves prognosis and survival in papillary thyroid carcinoma (PTC) patients
      without suspicion of lymph node metastases either clinically or on
      ultrasonography. It is possible that in such patients the use of lymphatic
      mapping and sentinel lymph node (SLN) biopsy, as are employed for other tumours,
      will be of assistance. The aim of this study was to evaluate the feasibility of
      preoperative 99mTc-nanocolloid lymphoscintigraphy and an intra-operative SLN
      procedure in the management of PTC patients. METHODS: Twenty-five consecutive
      patients were entered in the study between April 2005 and October 2005. All had a
      preoperative diagnosis of malignancy obtained by fine-needle aspiration cytology
      (FNAC), without clinical or ultrasonographic evidence of loco-regional lymph node
      involvement. Patients underwent preoperative lymphoscintigraphy after the
      injection of 99mTc-nanocolloid [median 6 MBq (range 4-9 MBq) in 0.1-0.2 ml saline
      injected intratumorally under ultrasound guidance] and an intra-operative SLN
      procedure using a hand-held gamma probe. Surgery was performed by the same
      surgeon in all patients. RESULTS: Preoperative lymphoscintigraphy identified at
      least one SLN in all patients. During surgery, using the gamma probe, the surgeon
      was able to find at least one SLN in all cases. A good correlation was found
      between preoperative imaging and probe results. Metastasis was found in at least
      one SLN in 12 (48%) patients. In seven (28%) patients the involved SLN was the
      most radioactive SLN, while in five (20%) patients a less radioactive SLN was
      involved by malignancy. Ten of these 12 patients had only micrometastases (<2
      mm). Micrometastases were found in the most radioactive SLN in six cases and in
      less radioactive SLNs in four cases, while in two patients more lymph nodes
      visualised at lymphoscintigraphy ipsilateral to the primary tumour were sites of
      metastasis. CONCLUSION: The rate of nodal involvement was very high in our
      series: in 48% of patients at least one metastatic lymph node was found. From a
      technical point of view the intra-operative SLN procedure in PTC patients was
      easy to perform, without major intra-operative complications. Our promising
      preliminary experience needs to be confirmed in larger series of patients series
      with longer follow-up.

PMID- 17235531
TI  - Success is a matter of experience: type 1 tympanoplasty : influencing factors on
      type 1 tympanoplasty.
AB  - Our objective was to identify the factors that could influence the success rate
      of type 1 tympanoplasty in a tertiary care centre where both residents and senior
      surgeons perform this operation. Six hundred and seven patients who had been
      performed type 1 tympanoplasty as a primary otologic surgery between January 1997
      and December 2004 were retrospectively chart reviewed. The patients had intact
      and mobile ossicular chain peroperatively. Patients with any other macroscopic
      otologic pathology like cholesteatoma, granulation in the middle ear and osteitis
      in mastoid cells were excluded from the study. Dry ear, intact and mobile
      tympanic membrane, improvement of the hearing by at least 10 dB and air-bone gap
      less than 25 dB were accepted as success criteria after 12 months of follow-up
      period. Chi-square test was used for statistical comparison of the different
      influencing factors. The male gender, younger age, smaller-sized perforations and
      experience of the surgeon were stated as good prognostic factors due to
      statistical evaluation. Afterwards the data of the study group was reanalysed in
      order to decide the cases for the residents. Finally, it was observed that
      seniors had better results in cases with perforations greater than 50%, dry ears
      and patients older than 16 years. In training and research clinics where both
      residents and senior surgeons perform type 1 tympanoplasty, the rate of success
      can be enhanced if patients with perforations greater than 50%, dry ears and
      patients older than 16 years are operated by the senior surgeons. The reason for
      this is that these groups have the overall worse results and should by argument
      be done by senior surgeons.

PMID- 17235532
TI  - Basaloid squamous cell carcinoma of the external auditory canal: case report.
AB  - Basaloid squamous cell carcinoma (BSCC) is a rare malignancy, with features of
      both basal cell carcinoma and squamous cell carcinoma. The tumor has a
      predilection for the upper aerodigestive tract, and has been suggested to behave
      more aggressively than squamous cell carcinoma (SCC). To the author's knowledge,
      BSCC confined to the external auditory canal (EAC) has not been previously
      described. BSCC of EAC manifests similar characteristics as the conventional EAC
      cancer, presenting a mass with chronic otorrhea and itching sense. Excision of
      the tumor was accomplished by modified lateral temporal bone resection. This
      report describes the first case of BSCC in this location, and includes reviews of
      the pathologic and clinical aspects of this disease.

PMID- 17235533
TI  - Laser surgery of T1a glottic carcinomas; significance of resection margins.
AB  - Since 1995 patients with T1a glottic carcinomas have been treated with laser
      surgery at the Department of Otorhinolaryngology, Rikshospitalet in Oslo. During
      this period we have in many cases noticed an inconsistency between the clinical
      outcome and the histopathological report describing that the resection margins
      were not free. We wanted to investigate this discrepancy, and the charts with the
      histopathological reports of 171 patients treated between 1995 and 2005 have been
      reviewed. Seventeen patients (10%) experienced a recurrence of the initial
      disease and were treated by repeated laser surgery, radiotherapy, or radiotherapy
      and laryngectomy. Two patients (1%) had died from the disease. In 36% of the
      cases (62 patients) the histopathological report indicated "not free" or
      "probably not free" resection margins. The discrepancy between the
      histopathological reports and the clinical outcome reflects the pathologist's
      difficulty in orienting and determining resection margins in laser-resected
      specimens. Because of the low number of recurrences or metastases, the verdict of
      a violated resection margin should probably not be crucial for further treatment.
      The surgeon's peroperative judgement may be trusted, however, with very close
      follow-up in order to detect early recurrences.

PMID- 17235534
TI  - Cavernous hemangioma of the internal auditory canal.
AB  - Hemangiomas rarely occur in the internal auditory canal. These tumors originate
      from the capillary bed of the epineurium surrounding the nerve and can either
      compress or infiltrate the nerve. Depending on location and the nerve of origin,
      these lesions can cause severe and progressive sensorineural hearing loss,
      tinnitus, facial nerve palsy, or vertigo even when they are relatively small. The
      presence of a small contrast-enhancing tumor in the internal auditory canal
      accompanied by severe sensorineural hearing loss and facial nerve palsy, should
      raise the suspicion of a hemangioma. Early recognition and surgical intervention
      in these benign tumors may improve the chance of preserving the functional
      integrity of the facial nerve and provides better results after nerve
      reconstruction. Due to their relative small size, the temporal bone CT-scan may
      show no evidence of pathological widening of the internal auditory canal or the
      typical intralesional calcifications at the time of presentation. MRI with
      Gadolinium is the imaging method of choice and a high index of clinical suspicion
      is necessary for the diagnosis of these tumors. In this paper we report about a
      51-year-old male presented with right-sided sensory-neural deafness and facial
      nerve palsy, accompanied by severe tinnitus and ipsilateral loss of vestibular
      function due to a cavernous hemangioma in the internal auditory canal.

PMID- 17235535
TI  - Ultrasound in the diagnosis of developmental dysplasia of the hip in newborns.
      The European approach. A review of methods, accuracy and clinical validity.
AB  - Based on soft evidence that ultrasound screening tends to reduce the rate of late
      developmental dysplasia of the hip (DDH) and the need for surgical interventions,
      different screening strategies including universal or selective ultrasound
      screening have been established in several European countries and centres during
      the last decade. We performed an extensive search for articles on ultrasound
      diagnosis of developmental dysplasia of the hip over the last 26 years. A few
      studies reported an adequate repeatability for the static [Graf, Morin, modified
      Morin (Terjesen)] and for the combined static/dynamic methods [modified Graf
      (Rosendahl)], while no such reports were found for the dynamic (Harcke)
      ultrasound techniques. The effect of newborn ultrasound screening on late DDH
      have been addressed in two randomised trials (RCTs), both concluding that both
      selective and universal ultrasound screening tend to reduce the prevalence of
      subluxed or dislocated DDH, thus without reaching statistical significance.
      Finally, several observational studies have shown that morphologically normal
      hips tend to remain normal with or without a co-existing instability, and 97% of
      sonographically immature hips tend to normalise spontaneously within 3 months.
      Two studies report on a similar pattern for mildly dysplastic, but stable hips.
      From the data available we suggest that selective ultrasound screening is
      worthwhile in areas with a high prevalence of late cases, given a well-organised,
      high-quality service can be provided.

PMID- 17235537
TI  - A comparative study of satellite and ground-based phenology.
AB  - Long time series of ground-based plant phenology, as well as more than two
      decades of satellite-derived phenological metrics, are currently available to
      assess the impacts of climate variability and trends on terrestrial vegetation.
      Traditional plant phenology provides very accurate information on individual
      plant species, but with limited spatial coverage. Satellite phenology allows
      monitoring of terrestrial vegetation on a global scale and provides an
      integrative view at the landscape level. Linking the strengths of both
      methodologies has high potential value for climate impact studies. We compared a
      multispecies index from ground-observed spring phases with two types (maximum
      slope and threshold approach) of satellite-derived start-of-season (SOS) metrics.
      We focus on Switzerland from 1982 to 2001 and show that temporal and spatial
      variability of the multispecies index correspond well with the satellite-derived
      metrics. All phenological metrics correlate with temperature anomalies as
      expected. The slope approach proved to deviate strongly from the temporal
      development of the ground observations as well as from the threshold-defined SOS
      satellite measure. The slope spring indicator is considered to indicate a
      different stage in vegetation development and is therefore less suited as a SOS
      parameter for comparative studies in relation to ground-observed phenology.
      Satellite-derived metrics are, however, very susceptible to snow cover, and it is
      suggested that this snow cover should be better accounted for by the use of newer
      satellite sensors.

PMID- 17235536
TI  - Proton MR spectroscopy of the brain at 3 T: an update.
AB  - Proton magnetic resonance spectroscopy ((1)H-MRS) provides specific metabolic
      information not otherwise observable by any other imaging method. (1)H-MRS of the
      brain at 3 T is a new tool in the modern neuroradiological armamentarium whose
      main advantages, with respect to the well-established and technologically
      advanced 1.5-T (1)H-MRS, include a higher signal-to-noise ratio, with a
      consequent increase in spatial and temporal resolutions, and better spectral
      resolution. These advantages allow the acquisition of higher quality and more
      easily quantifiable spectra in smaller voxels and/or in shorter times, and
      increase the sensitivity in metabolite detection. However, these advantages may
      be hampered by intrinsic field-dependent technical issues, such as decreased T(2)
      signal, chemical shift dispersion errors, J-modulation anomalies, increased
      magnetic susceptibility, eddy current artifacts, challenges in designing and
      obtaining appropriate radiofrequency coils, magnetic field instability and safety
      hazards. All these limitations have been tackled by manufacturers and researchers
      and have received one or more solutions. Furthermore, advanced (1)H-MRS
      techniques, such as specific spectral editing, fast (1)H-MRS imaging and
      diffusion tensor (1)H-MRS imaging, have been successfully implemented at 3 T.
      However, easier and more robust implementations of these techniques are still
      needed before they can become more widely used and undertake most of the clinical
      and research (1)H-MRS applications.

PMID- 17235538
TI  - Air movement preferences observed in office buildings.
AB  - Office workers' preferences for air movement have been extracted from a database
      of indoor environmental quality surveys performed in over 200 buildings.
      Dissatisfaction with the amount of air motion is very common, with too little air
      movement cited far more commonly than too much air movement. Workers were also
      surveyed in a detailed two-season study of a single naturally ventilated
      building. About one-half the building's population wanted more air movement and
      only 4% wanted less. This same ratio applied when the air movement in workspaces
      was higher than 0.2 m/s, the de facto draft limit in the current ASHRAE and ISO
      thermal environment standards. Preference for "less air motion" exceeded that for
      "more" only at thermal sensations of -2 (cool) or colder. These results raise
      questions about the consequences of the ASHRAE and ISO standards' restrictions on
      air movement, especially for neutral and warm conditions.

PMID- 17235539
TI  - Prevalence of cold-related complaints, symptoms and injuries in the general
      population: the FINRISK 2002 cold substudy.
AB  - The prevalence of cold-related complaints and symptoms in the general population
      has remained unknown. As part of the nationwide FINRISK 2002 health survey
      performed in Finland, 8,723 people aged 25-64 years filled in a questionnaire
      asking about the number of hours spent weekly in cold air, their sensations
      during cold exposure, cold-related complaints, symptoms of diseases, and
      degradation of performance. Cold thermal sensations at +5 degrees C to -5 degrees
      C were reported by 35% of men and 46% of women. Almost all subjects reported at
      least some cold-related complaints, most commonly musculoskeletal pain (men 30%,
      women 27%), followed by respiratory (25% / 29%), white finger (15% / 18%) and
      episodic peripheral circulation symptoms (12% / 15%). Decreased mental or
      physical performance in cold was reported by 75% of men and 70% of women, most
      commonly impairing manual dexterity and tactile sense. With declining
      temperature, the first symptom to emerge was pain in the elbow or the forearm (at
      -3 degrees C), followed by increased excretion of mucus from the lungs (-5
      degrees C), while most other symptoms appeared only at lower temperatures of -15
      degrees C to -20 degrees C. Most symptoms showed little or no association with
      the weekly duration of exposure, with the exception of cold-induced pain at most
      sites. Although, in general, Finns are well adapted to the cold climate, the high
      prevalence of cold-related complaints poses a challenge to the health care system
      in terms of decreased performance and the possibility that such symptoms predict
      more serious health effects, such as increased mortality.

PMID- 17235540
TI  - [Positioning therapy in intensive care medicine in Germany. Results of a national
      survey].
AB  - BACKGROUND: The effects of a systematic change in a patient's position [prone
      position, continuous lateral rotational therapy (CLRT)] have been investigated in
      recent years in acute lung injury and have shown an improvement in oxygenation,
      but controversial results regarding duration of mechanical ventilation, intensive
      care treatment and mortality compared to conventionally treated patients. We were
      interested in the practice and acceptance of positioning therapy in German
      intensive care units (ICU) and performed a national postal survey with respect to
      evaluation of indications, preference of particular positions, observed
      complications and additional aspects (costs, influence on other intensive care
      measures etc.). METHODS: A questionnaire (12 multiple choice items) was sent to
      1,763 ICUs, which were identified from the "Deutsches Krankenhausadressbuch"
      (German hospital address book 2005). The analysis was performed anonymously.
      RESULTS: A total of 702 questionnaires (40.4%) were returned and analysed. The
      135 degrees position (incomplete prone position) was most frequently used (50%),
      while the prone position (25%) and CLRT (18%) were less frequent. The improvement
      in oxygenation (95%) and the prevention of ventilator-associated complications
      (75.7%) were important indications for positioning therapy. Results of a blood
      gas analysis provided the necessary criteria for determining positional therapy.
      Supporters of the prone position advocated lower cost and better efficacy in
      comparison to CLRT. The frequency of complications during positioning therapy was
      reported to be high: hemodynamic instability (73.6%), accidental loss of
      tube/catheters (50.4%) and patient intolerance (40.7%) were often observed, and
      complication-free positioning therapy was reported in only 8.6%. CONCLUSIONS: The
      135 degrees position (incomplete prone position) is the most frequently used
      positioning therapy in Germany for improvement of oxygenation in patients with
      acute lung injury. Prone position and CLRT are less frequently used, probably due
      to an increased frequency of (expected) complications. The authors assume that
      clear guidelines and algorithms are needed to establish a more routine, safe
      practical application and a reduction in the complication rate.

PMID- 17235541
TI  - [German Refined-Diagnosis Related Groups, version 2007. The depiction of
      intensive care medicine].
AB  - Since the G-DRG system was introduced in Germany in 2004, attempts have been made
      to model medical services performed in the intensive care units on a performance
      oriented system by capitation. Based on this background the InEK, the institution
      which is responsible for design and development of the G-DRG system, has
      implemented several new issues into the version for 2007 which will be presented
      in this article. On the one hand the changes concerning the coding rules of
      diagnosis and procedures will be described and on the other hand important
      topics, such as "multimodal intensive care" or "complex treatment of patients
      with severe infections by multi-resistant pathogens", will be focused on.
      Furthermore, some new developments concerning the global functions ("complex
      procedures", "complex intensive treatment") as well as the changes in the coding
      rule for the demographic factor "mechanical ventilation" will be discussed.
      Finally, the regulations for additional remuneration are updated. In general, the
      attempts of the InEK to improve the G-DRG mapping for intensive care medicine are
      welcome and constructive. The regulations provided seem to be beneficial, but at
      the same time complicating the instructions. Hence, standardisation of intensive
      care medicine via diagnosis-related-groups still remains inadequate and therefore
      unsatisfactory in 2007.

PMID- 17235542
TI  - [Remifentanil-propofol versus fentanyl-midazolam combinations for intracranial
      surgery: influence of anaesthesia technique and intensive sedation on ventilation
      times and duration of stay in the ICU].
AB  - INTRODUCTION: After neurosurgery patients often need to be sedated and ventilated
      in the intensive care unit (ICU). However, rapid postoperative recovery and
      neurological examination are particularly important for the early recognition of
      complications. In this retrospective study two different strategies of
      anaesthesia technique and ICU sedation (fentanyl-midazolam versus remifentanil
      propofol) were compared. METHODS: Intraoperatively, patients received continuous
      infusions of either fentanyl (0.2-1.0 mg/h) and midazolam (2-10 mg/h) or
      remifentanil (0.2-0.5 microg/kg body weight/min) and propofol (3-6 mg/kg body
      weight/h). After arrival in the ICU fentanyl (0.03-0.2 mg/h) and midazolam (2-12
      mg/h) or remifentanil (0.1-0.2 microg/kg body weight/min) and propofol (0.5-3
      mg/kg body weight/h) were infused to reach a Ramsay score of 4. The times between
      termination of infusion and extubation and the length of stay in the ICU were
      examined. RESULTS: A total of 60 patients (n=30 each group) undergoing
      supratentorial brain tumour surgery were enrolled. The groups were comparable for
      age, weight, ASA status (American Society of Anesthesiologists) and duration of
      drug administration (remifentanil-propofol 528+/-382 min versus fentanyl
      midazolam 548+/-360 min). Extubation times were significantly shorter after
      remifentanil-propofol (47 min) than after fentanyl-midazolam (481 min), and the
      length of stay in the ICU was also significantly reduced (1.8 days versus 3.7
      days). As a result of prolonged unconsciousness and impaired neurological
      assessability, a brain CT scan was necessary in 3 patients after fentanyl
      midazolam to exclude neurosurgical complications. CONCLUSION: This retrospective
      study demonstrates that remifentanil-propofol anaesthesia and ICU sedation are
      superior to the combination of fentanyl and midazolam in terms of ventilation
      time and length of ICU stay. Moreover, the use of fentanyl-midazolam may lead to
      unnecessary CT scans.

PMID- 17235544
TI  - [Myotoxicity of local anaesthetics: experimental myth or clinical truth?].
AB  - Intramuscular injections of local anaesthetic agents regularly result in
      reversible muscle damage, with a dose-dependent extent of the lesions. All local
      anaesthetic agents that have been examined are myotoxic, whereby procaine
      produces the least and bupivacaine the most severe muscle injury. The
      histological pattern and the time course of skeletal muscle injury appear
      relatively uniform: hypercontracted myofibrils become evident directly after
      injection, followed by lytic degeneration of striated muscle sarcoplasmic
      reticulum myocyte edema and necrosis. Intriguingly, in most cases myoblasts,
      basal laminae and connective tissue elements remain intact which subsequently
      ensures complete muscular regeneration. Subcellular pathomechanisms of local
      anaesthetic myotoxicity are still not understood in detail. Increased
      intracellular Ca(2+) levels are suggested to be the most important element in
      myocyte injury, since denervation, inhibition of sarcolemmal Na(+) channels and
      direct toxic effects on myofibrils have been excluded as sites of action.
      Although experimental myotoxic effects are impressively intense and reproducible,
      only few case reports of myotoxic complications in patients after local
      anaesthetic administration have been published. In particular, the occurrence of
      clinically relevant myopathy and myonecrosis has been described after continuous
      peripheral blockades, infiltration of wound margins, trigger point injections,
      peribulbar and retrobulbar blocks.

PMID- 17235545
TI  - Colony growth of Philippine isolates of Blastocystis hominis in simplified, soft
      agar medium.
AB  - The agar-cloning technique of Blastocystis hominis has been observed in both
      solid and semisolid agar using Iscove's modified Dulbecco's medium. In this
      study, Philippine isolates of B. hominis were grown by pour-plate method in
      semisolid agar using Locke's solution. Inoculated plates contained 0.7% agar, 10%
      horse serum, and 0.1% sodium thioglycollate. Plates were incubated at 37 degrees
      C in a microaerophilic jar for 7-10 days. Biconvex disk-shaped colonies were seen
      abound at the bottom half of the medium. Colonies growing at the agar-glass
      interface were flat and consisted of thin layers of cells. From these colonies,
      large amoeboid cells were frequently seen on the periphery, whereas smaller cells
      were concentrated at the core. Analysis of the SSU rDNA genetically established
      the identity of the clones to be B. hominis. This is the first report on agar
      cloning of Blastocystis in a compound medium.

PMID- 17235546
TI  - Ultrastructure of the spermatozoon of Bothriocephalus claviceps (Cestoda,
      Pseudophyllidea): a parasite of Anguilla anguilla (Fish, Teleostei).
AB  - The mature Bothriocephalus claviceps spermatozoon is filiform and tapered at both
      extremities. It contains two axonemes of unequal lengths of the 9+"1" pattern of
      the trepaxonemata. The anterior extremity exhibits an apical cone of an electron
      dense material about 6.6 microm long by 0.2 microm wide at its base and a crest
      like body making an angle of about 40 degrees with the spermatozoon axis. It is
      spiralized around the whole extremity of the spermatozoon. The nucleus is a cord
      of electron-dense material that interposes itself between the two axonemes. The
      cortical microtubules are of two types: hollow-centred and electron-dense
      centred. The cytoplasm is slightly electron dense and contains numerous electron
      dense granules in regions III, IV, and V of the spermatozoon. The anterior and
      posterior extremities of the spermatozoon contain a single axoneme. The presence
      of an apical cone of the electron dense material has never, to our knowledge,
      been reported in the Pseudophyllidea. In addition, we show for the first time the
      existence of a crested body in the Bothriocephalidae.

PMID- 17235547
TI  - An ultrastructural study of reproduction in the sporocysts of Prosorhynchoides
      gracilescens (Digenea: Bucephalidae).
AB  - The germinal development in Prosorhynchoides gracilescens sporocysts was studied
      using electron microscopy. The germinal cells proliferated and developed within
      multiple floating germinal masses located in the terminal portions of sporocyst
      branches. The germinal masses were composed of supporting and germinal cells.
      Supporting cells possessed numerous flattened extensions that spread around and
      between developing germinal cells to form three-dimensional mesh network, which
      maintained the integrity of the germinal mass. Morphological evidences of close
      interactions between supporting and germinal cells were numerous gap junctions
      between the two cell types and phagocytosis of small fragments of germinal cells
      cytoplasm by supporting cells. The germinal cells displayed structural
      differences that seemed to reflect their sequential developmental changes. These
      changes included (1) cell growth and increase of organelles number, (2)
      dispersion of nuclear chromatin and increase of nucleolus size, (3) polarization
      of the cell, (4) appearance of specific structures such as nuage and laminated
      inclusions. The germinal cells left the germinal masses to finish their
      differentiation in the body cavity and then cleaved to give rise to cercarial
      embryos. Ultrastructural features of the germinal elements of P. gracilescens
      sporocysts are discussed in the light of existing controversy concerning the
      nature of the germinal sacs reproduction.

PMID- 17235549
TI  - Is mesangial hypercellularity with glomerular immaturity a variant of
      glomerulosclerosis?
AB  - Our aim was to correlate an immunohistochemical pattern of selected podocyte
      cytoskeleton-associated proteins in children diagnosed with focal segmental
      glomerulosclerosis (FSGS) and diffuse mesangial proliferation accompanied by
      glomerular immaturity (Im-DMP) with the clinical courses of both diseases. The
      material included 33 renal biopsies obtained from children diagnosed with DMP
      with or without signs of glomerular immaturity (ten and 15 participants,
      respectively) or FSGS (eight patients). Ezrin, podocalyxin, synaptopodin and
      nephrin expression was evaluated by immunohistochemical assay. A positive
      reaction for ezrin, podocalyxin, synaptopodin and nephrin was observed in the
      most superficial, continuous 'layer' of podocytes in Im-DMP patients. This
      distribution closely mimicked the immunohistochemical pattern observed in FSGS.
      The severe initial course of Im-DMP was transient. Resistance to steroids (six
      children) and renal insufficiency (two patients) in these subjects subsided,
      whilst, in the FSGS patients, the resistance to steroids recognized in all the
      children and the renal insufficiency diagnosed in three of them were still
      present. Mimicry between the immunohistochemical pattern of glomerular immaturity
      in DMP and focal segmental glomerulosclerosis might explain the severe initial
      course of this nephrotic syndrome in children. The transient clinical character
      of the former may also indicate that it is not a variant of FSGS.

PMID- 17235548
TI  - Linkage between mitochondrial cytochrome b lineages and morphospecies of two
      avian malaria parasites, with a description of Plasmodium (Novyella) ashfordi sp.
      nov.
AB  - Numerous lineages of avian malaria parasites of the genus Plasmodium have been
      deposited in GenBank. However, only seven morphospecies have been linked to these
      lineages. This study linked two molecular sequences with morphospecies of malaria
      parasites. Two species of Plasmodium (mitochondrial cytochrome b gene lineages P
      GRW2 and P-GRW4) were isolated from naturally infected adult great reed warblers
      (Acrocephalus arundinaceus) and inoculated to naive juvenile individuals of the
      same host species. Heavy parasitemia developed in the subinoculated birds, which
      enable identification of the species and deposition of their voucher specimens.
      Parasites of the lineage P-GRW2 were described as a new species, Plasmodium
      (Novyella) ashfordi, which is characterized primarily by the fan-like mature
      erythrocytic meronts containing seven to eight merozoites and the terminal
      position of clumped pigment granules in the gametocytes. Illustrations of the
      blood stages of the new species and Plasmodium (Haemamoeba) relictum (lineage P
      GRW4) are given. The parasites of both lineages are transmitted in Africa and
      probably not in northern Europe. Other lineages closely related to P. ashfordi
      and P. relictum are identified. This study establishes the value of PCR-based
      identification of avian malaria parasites.

PMID- 17235550
TI  - Fifteen-year remission of a steroid-resistant nephrotic syndrome sustained by
      cyclosporine A.
AB  - Many children with a late steroid-resistant nephrotic syndrome (SRNS) and focal
      glomerulosclerosis have a poor prognosis and enter end-stage renal failure (ESRF)
      within five years. Reports are scarce on the long-term follow-up of patients
      entering remission while receiving immunosuppressive therapy after steroids have
      failed. A two-year-old boy with focal and segmental glomerulosclerosis having
      both late steroid and cyclophosphamide resistance entered complete remission of
      the SRNS almost two years after starting induction therapy with cyclosporine A
      (CSA). During the 15-year follow-up, the patient experienced five relapses during
      CSA maintenance therapy. All relapses were successfully treated within 10 days by
      intravenous methylprednisolone pulses in addition to CSA. The relapses were
      accompanied by a drop in the glomerular filtration rate (GFR). At the age of 18
      years, the patient had grade II chronic kidney disease (GFR=61 ml/min/1.73 m2).
      At the age of 14 years, mycophenolate mofetil (MMF) was added to the maintenance
      therapy and the CSA dosage was reduced. Two renal biopsies at the ages of 10 and
      18 years failed to detect CSA nephrotoxicity. We conclude that children with SRNS
      may have long-term benefit from a combination therapy using intravenous
      methylprednisolone pulses and CSA.

PMID- 17235551
TI  - Non-Hodgkin lymphoma with t(14;18): clonal evolution patterns and cytogenetic
      pathologic-clinical correlations.
AB  - PURPOSE: The pattern and frequency of secondary chromosome abnormalities in
      t(14;18)-carrying non-Hodgkin lymphomas (NHL) were evaluated for differences in
      relation to histologic NHL subtype and patients' outcome. METHODS: One hundred
      and forty-nine NHL patients with t(14;18) and complete cytogenetic, morphologic,
      and clinical information were selected. RESULTS: One hundred and twelve cases
      were follicular lymphoma (FL) and 37 were diffuse large B-cell lymphoma (DLBCL).
      One hundred and forty cases showed secondary aberrations (94%, median = 6.0). The
      most frequent were losses from chromosome arms 1p and 6q and +7 (26%). Loss from
      1q, +7, and +12 were more frequent in DLBCL than in FL. Loss from 1p, Xp, and -16
      were more frequent in FL grade 3 than in FL grades 1 and 2. Patients with <6.0
      secondary cytogenetic aberrations had better prognosis than did those with a
      higher number of aberrations. Trisomy 21 was associated with shorter patient
      survival. FLIPI score, the number of secondary chromosomal aberrations, and +21
      were all of independent prognostic value in Cox multivariate analysis. FL grade 1
      3a patients that had received chemotherapy, showed a higher frequency of i(6p)
      and loss from 6q. CONCLUSION: Secondary chromosomal aberrations showed some
      correlation with the morphologic subgroups of t(14;18)-NHL. Trisomy 21 and the
      presence of >6.0 secondary cytogenetic aberrations both correlated with shorter
      overall survival.

PMID- 17235552
TI  - Ectomycorrhiza communities of red oak (Quercus rubra L.) of different age in the
      Lusatian lignite mining district, East Germany.
AB  - Ectomycorrhizal (ECM) communities were assessed on a 720 m(2) plot along a
      chronosequence of red oak (Quercus rubra) stands on a forest reclamation site
      with disturbed soil in the lignite mining area of Lower Lusatia (Brandenburg,
      Germany). Adjacent to the mining area, a red oak reference stand with undisturbed
      soil was investigated reflecting mycorrhiza diversity of the intact landscape.
      Aboveground, sporocarp surveys were carried out during the fruiting season in a 2
      week interval in the years 2002 and 2003. Belowground, ECM morphotypes were
      identified by comparing sequences of the internal transcribed spacer regions from
      nuclear rDNA with sequences from the GenBank database. Fifteen ECM fungal species
      were identified as sporocarps and 61 belowground as determined by
      morphological/anatomical and molecular analysis of their ectomycorrhizas. The
      number of ECM morphotypes increased with stand age along the chronosequence.
      However, the number of morphotypes was lower in stands with disturbed soil than
      with undisturbed soil. All stands showed site-specific ECM communities with low
      similarity between the chronosequence stands. The dominant ECM species in nearly
      all stands was Cenococcum geophilum, which reached an abundance approaching 80%
      in the 21-year-old chronosequence stand. Colonization rate of red oak was high
      (>95%) at all stands besides the youngest chronosequence stand where colonization
      rate was only 15%. This supports our idea that artificial inoculation with site
      adapted mycorrhizal fungi would enhance colonization rate of red oak and thus
      plant growth and survival in the first years after outplanting.

PMID- 17235553
TI  - Merck fellowships contribute to the continued growth of clinical pharmacology in
      Sweden.
AB  - Since 1990, Merck, Sharpe & Dohme, Sweden, has created fellowships for physicians
      embarking upon a career in clinical pharmacology at Swedish medical schools. The
      fellowship has provided full salary at the level of a resident in clinical
      medicine for an average period of 1-2 years. Between 1992 and 2004, 22 fellows
      representing all six medical schools were selected for a fellowship. Of these, 20
      have received specialties in clinical pharmacology, 11 now (2006) have positions
      as physicians in clinical pharmacology in university hospitals, 7 in the
      pharmaceutical industry, and 2 in a drug control agency. Two have not yet
      completed their training. The fellowships have been granted on the basis of
      excellence in clinical pharmacological problem-oriented research. The peer review
      of the applications has been performed by academic professors in clinical
      pharmacology and the chairperson of the Swedish Society of Clinical Pharmacology.
      The importance of having a donor with serious dedication to training and research
      and a scholarship organization that can prioritize these goals in an unbiased way
      are underlined. The Swedish MSD fellowships are a valuable complement to the
      resources provided by society to support the development of clinical
      pharmacology, i.e. the health care organizations, the faculties in medicine, and
      various research foundations.

PMID- 17235554
TI  - Prevalence of antibiotic resistance in Escherichia coli: overview of
      geographical, temporal, and methodological variations.
AB  - The increase in bacterial antibiotic resistance is of major concern worldwide,
      but pertinent epidemiologic studies have used strongly divergent approaches and
      are widely scattered in the literature. The aim of this study was to conduct a
      systematic review of studies reporting on the prevalence of antibiotic resistance
      in Escherichia coli in different parts of the world. Studies published from 1970
      to 2006 on the prevalence of E. coli resistance were identified by a systematic
      Medline research and reviewed with respect to characteristics of the study design
      and study population, the method of resistance detection, and the prevalence of
      resistance. The prevalence of resistance to specific antibiotics was highly
      variable in different populations and in different countries and ranged from 0 to
      100%. The prevalence of resistance reported in studies from Middle and South
      America, Spain, and Turkey was higher than that reported in the USA and Central
      Europe. Moreover, a tendency towards higher prevalence rates of resistance in
      recent years was observed. The findings indicate a need for regular monitoring of
      antimicrobial susceptibility rates in different human and animal populations by
      standardized sampling and measurement procedures. Such monitoring would help
      identify relevant factors that contribute to the spread of resistant pathogens
      and would support the prudent use of antibiotics.

PMID- 17235555
TI  - Genotypic analysis of Asp299Gly and Thr399Ile polymorphism of Toll-like receptor
      4 in systemic autoimmune diseases of Korean population.

PMID- 17235558
TI  - [Investigation of the accuracy of various techniques for measuring the
      epicondylar axis].

PMID- 17235556
TI  - Preliminary evaluation in rheumatoid arthritis activity in patients treated with
      TNF-alpha blocker plus methotrexate versus methotrexate or leflunomide alone.
AB  - Methotrexate (MTX) is a first-line disease-modifying antirheumatic drugs (DMARD)
      in rheumatoid arthritis (RA). Leflunomide (LEF) and the biologic agents entered
      the arsenal of DMARDs in 1998. Therapeutic properties of new drugs are still
      under survey. The purpose of this study was to evaluate and compare the efficacy
      of MTX, LEF and a biologic agent (TNF-alpha blocker) combined with MTX in
      reducing disease activity in RA. Seventy-eight patients with active RA underwent
      a 24-week treatment with MTX 15 mg/week (30 pts), LEF 20 mg/day (30 pts) or a TNF
      alpha blocker (etanercept 25 mg 2x weekly or infliximab 3 mg/kg in the week 0, 2,
      6 and every 8 weeks thereafter) plus MTX 15 mg/week (18 pts). Only patients with
      RA resistant to MTX were included in groups receiving LEF or a biologic agent.
      During follow-up, patients' characteristics, disease characteristics, and
      clinical and laboratory data were registered. RA activity was evaluated using the
      ESR, tender and swollen joint counts, the duration of morning stiffness, disease
      activity score-28 (DAS 28), visual analogue scale (VAS) and health assessment
      questionnaire (HAQ). Treatment efficacy was demonstrated with ACR 20, 50 and 70
      criteria. All groups revealed statistically significant improvement in all
      disease activity parameters measured. The percentage improvements were similar in
      groups treated with MTX and LEF and--except for VAS--significantly greater in the
      group treated with a biologic agent. Disease activity assessed by DAS 28
      decreased significantly in all groups: the results were comparable in groups
      treated with MTX and LEF and significantly more prominent in the group treated
      with a TNF-alpha blocker. The ACR 20, 50 and 70 improvements amounted,
      respectively: 100, 50 and 7% in MTX group 87, 60 and 13% in LEF group and 100, 83
      and 50% in a biologic agent group. The study revealed equal effectiveness of MTX
      and LEF in reducing disease activity in rheumatoid arthritis. The efficacy of a
      TNF-alpha blocker combined with MTX was higher than that of each conventional
      DMARDs, especially with regard to ACR 70 criteria (considerable improvement after
      treatment). LEF was equally effective as MTX in patients unable to continue MTX
      treatment due to the drug's ineffectiveness.

PMID- 17235557
TI  - Liquid medium and liquid overlays improve embryogenic tissue initiation in
      conifers.
AB  - Somatic embryogenesis (SE) is expected to play an important role in increasing
      productivity, sustainability, and uniformity of future US forests. For commercial
      use, SE technology must work with a variety of genetically diverse trees.
      Initiation in loblolly pine (Pinus taeda L.), the main commercial US forest
      species, is often recalcitrant for desirable genotypes. Liquid initiation medium
      with no or low gelling agent or placement of the explant on gelled medium
      followed later by a liquid medium overlay during the initiation process increased
      initiation for loblolly pine and Norway spruce (Picea abies). Loblolly pine
      liquid medium required reduction of NAA from 2 mg/l in gelled medium to 0.3 mg/l
      in liquid medium. Once the NAA concentration was adjusted, loblolly pine
      initiation occurred in liquid medium with fully immersed megagametophytes,
      explants supported at the liquid medium surface, or on gelled medium overlaid
      with liquid medium. Liquid overlays (0.25 ml) consisting of medium with NAA
      reduced to 0.3 mg/l, 9 mg/l ABA and no gelling agent applied to explants on 2 ml
      of gelled medium provided excellent initiation results. Greatest initiation
      percentages occurred when the liquid overlay was applied 14 days after placement
      of the megagametophyte on gelled medium. Initiation increases ranged from +8.5%
      with high-value cross-pollinated seed sources to +6.5 to +9.9% with open
      pollinated and often recalcitrant seed sources. Liquid medium addition allows
      rapid replenishment of nutrients and adjustment or change of pH, hormones, or
      other parameters without disturbing the tissue.

PMID- 17235559
TI  - [Internal fixation of meta- and diaphyseal intercalary bone defects after tumour
      resection with intramedullary nailing and porous polymethylmetacrylate (PMMA)
      spacer].
AB  - BACKGROUND: Radical resection of bone tumours localized in the meta- or diaphysis
      of long bones frequently results in segmental defects. Several stabilization
      techniques with preservation of the adjacent joint have been published, but the
      failure rate appears to be considerable. The objective of this study is the
      experimental and clinical testing of a new technique which combines unreamed
      nailing with support of the defect by a porous polymethylmetacrylate (PMMA)
      spacer. METHODS: For spacer preparation, PMMA spheres were adhered to a
      cylindrical spacer (O 32 mm) with interconnective porosity. Axial strength was
      determined, as was the stiffness/strengths of the combination osteosynthesis in
      human cadaver tibias (defect lengths 6 cm; empty defect served as a control). An
      experiment was also conducted with sheep. A 3 cm diaphyseal tibia defect was
      prepared and stabilized by nailing. For the control there was an empty defect.
      Group A had support of the defect with a PMMA spacer and group B a PMMA spacer
      coated with osteoconductive RGD-peptide. Evaluation after was made after 6 months
      including histology and a determination of relative torsional strength. In
      addition, a clinical study has been under way since October 1998, with 13
      patients (defect lengths between 3-15 cm) being operated. RESULTS: Axial
      stability was 12,750+/-300 N (17.56+/-0.59 MPa). There was an enhancement of 4
      point bending stiffness by 35% (P=0.028), of axial stiffness by 36% (ns) and of
      axial strength by 553% (P=0.028). Histology showed the formation of a new bone at
      the spacer/muscle interface. For the sheep, relative torsional strength was
      enhanced by 95% (P=0.08) in group A and by 91% (P=0.047) in group B. For the
      patients studied, the mean follow-up period was 16.1 months, max. 48 months. One
      mechanical failure occurred after 24 months, which was solved by callus
      distraction. CONCLUSIONS: Combination osteosynthesis is suitable for stabilizing
      segmental bone defects. The risk of mechanical failure appears to be low.
      Nevertheless, this technique should only be applied as a definitive solution if
      callus distraction is unfavourable due to advanced age or a poor lifetime
      prognosis. The method can also be used for temporary internal stabilization
      during prolonged postoperative chemotherapy.

PMID- 17235560
TI  - Dominance of Prevotella and low abundance of classical ruminal bacterial species
      in the bovine rumen revealed by relative quantification real-time PCR.
AB  - Relative quantification real-time PCR was used to quantify several bacterial
      species in ruminal samples from two lactating cows, each sampled 3 h after
      feeding on two successive days. Abundance of each target taxon was calculated as
      a fraction of the total 16S rRNA gene copies in the samples, using taxon-specific
      and eubacterial domain-level primers. Bacterial populations showed a clear
      predominance of members of the genus Prevotella, which comprised 42% to 60% of
      the bacterial rRNA gene copies in the samples. However, only 2% to 4% of the
      bacterial rRNA gene copies were represented by the classical ruminal Prevotella
      species Prevotella bryantii, Prevotella ruminicola and Prevotella brevis. The
      proportion of rRNA gene copies attributable to Fibrobacter succinogenes,
      Ruminococcus flavefaciens, Selenomonas ruminantium and Succinivibrio
      dextrinosolvens were each generally in the 0.5% to 1% range. Proportions for
      Ruminobacter amylophilus and Eubacterium ruminantium were lower (0.1% to 0.2%),
      while Butyrivibrio fibrisolvens, Streptococcus bovis, Ruminococcus albus and
      Megasphaera elsdenii were even less abundant, each comprising <0.03% of the
      bacterial rRNA gene copies. The data suggest that the aggregate abundance of the
      most intensively studied ruminal bacterial species is relatively low and that a
      large fraction of the uncultured population represents a single bacterial genus.

PMID- 17235561
TI  - Inventory and monitoring of wine microbial consortia.
AB  - The evolution of the wine microbial ecosystem is generally restricted to
      Saccharomyces cerevisiae and Oenococcus oeni, which are the two main agents in
      the transformation of grape must into wine by acting during alcoholic and
      malolactic fermentation, respectively. But others species like the yeast
      Brettanomyces bruxellensis and certain ropy strains of Pediococcus parvulus can
      spoil the wine. The aim of this study was to address the composition of the
      system more precisely, identifying other components. The advantages of the
      polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE)
      approach to wine microbial ecology studies are illustrated by bacteria and yeast
      species identification and their monitoring at each stage of wine production.
      After direct DNA extraction, PCR-DGGE was used to make the most exhaustive
      possible inventory of bacteria and yeast species found in a wine environment.
      Phylogenetic neighbor-joining trees were built to illustrate microbial diversity.
      PCR-DGGE was also combined with population enumeration in selective media to
      monitor microbial changes at all stages of production. Moreover, enrichment media
      helped to detect the appearance of spoilage species. The genetic diversity of the
      wine microbial community and its dynamics during winemaking were also described.
      Most importantly, our study provides a better understanding of the complexity and
      diversity of the wine microbial consortium at all stages of the winemaking
      process: on grape berries, in must during fermentation, and in wine during aging.
      On grapes, 52 different yeast species and 40 bacteria could be identified. The
      diversity was dramatically reduced during winemaking then during aging. Yeast and
      lactic acid bacteria were also isolated from very old vintages. B. bruxellensis
      and O. oeni were the most frequent.

PMID- 17235562
TI  - Nuclear metallothionein expression correlates with cisplatin resistance of
      ovarian cancer cells and poor clinical outcome.
AB  - Elevated metallothionein (MT) expression in ovarian cancers treated with
      cisplatin-based schemes represents an unfavorable prognostic index. MT expression
      is significantly higher in tumor samples obtained after chemotherapy. The present
      study aimed at examining MT expression in ovarian carcinoma cells sensitive
      (A2780) or resistant (A2780RCIS) against platinum drug treatment as well as
      examining effects of exposure to cisplatin on MT expression. Subcellular
      expression of MT was evaluated also in samples originating from 73 ovarian
      tumors. Cisplatin-resistant A2780RCIS cells were exposed to increasing cisplatin
      concentrations, and the subcellular expression of MT was determined by
      immunocytochemistry. The studies demonstrated that cisplatin-resistant A2780RCIS
      cells exposed to cisplatin typically manifested a nuclear MT expression. The
      study demonstrated also that exposure to cisplatin was paralleled by growing MT
      expression in cell nuclei. The nuclear expression of MT was also found to be
      specific for ovarian cancers of poor clinical outcome. No relationship could be
      demonstrated between cytoplasmic expression of MT and clinical variables. Nuclear
      MT expression is induced by cisplatin and seems to protect DNA in the cells from
      toxic effects of the drug.

PMID- 17235563
TI  - High PRL-3 expression in human gastric cancer is a marker of metastasis and
      grades of malignancies: an in situ hybridization study.
AB  - Phosphatase of regenerating liver (PRL)-3, encoding a 22-kD low molecular weight
      tyrosine phosphatase, has been reported to be associated with metastasis of
      colorectal carcinoma. We assessed the levels of PRL-3 mRNA expression to know
      whether its up-regulation was involved in progression and metastasis of gastric
      carcinoma. Levels of PRL-3 expression in 94 human gastric adenocarcinomas and 54
      matched lymph node metastases were detected by in situ hybridization and compared
      with clinicopathological characteristics including prognosis. High PRL-3
      expression was detected in 36.2% of primary gastric carcinoma (with nodal
      metastasis, 55.6%; without nodal metastasis, 10%; P < 0.001) and in 74.1% of
      lymph node metastases. The incidence of high PRL-3 expression in lymph node
      metastasis was significantly higher than in primary tumors (P < 0.044). Moreover,
      high expression of PRL-3 was closely associated with tumor size, lymphatic
      invasion, venous invasion, extent of lymph node metastasis, and tumor stage.
      These results suggest that high PRL-3 expression may participate in the
      progression and metastasis of gastric carcinoma. PRL-3 might be a novel molecular
      marker for aggressive gastric cancer.

PMID- 17235564
TI  - Aurora-B expression and its correlation with cell proliferation and metastasis in
      oral cancer.
AB  - Aurora-B kinase is a chromosomal passenger protein and is essential for
      chromosome segregation and cytokinesis. Aurora-B overexpression in various cancer
      cells induces chromosomal number instability to produce multinuclearity and
      relates to metastasis. Here, we examined the expression of Aurora-B in oral
      squamous cell carcinoma (OSCC) to elucidate the relationship between Aurora-B
      expression and clinico-pathological findings by immunohistochemistry. Aurora-B
      expression was observed in normal oral squamous epithelia and OSCC cases, but the
      number of positive cells was significantly higher in OSCC than in normal squamous
      epithelium (p < 0.01). The labeling index of Aurora-B was significantly
      correlated with lymph node metastasis (p < 0.01) and histological grades of
      differentiation (p < 0.01). We also compared Aurora-B expression with Ki-67
      expression and a positive correlation was found (p < 0.0001). Moreover, Aurora-B
      expression is significantly more frequent in multinuclear tumor cells than in
      total tumor cells. In summary, we found that Aurora-B expression was well
      correlated with cell proliferation, induction of multinuclear cells, histological
      differentiation, and metastasis in OSCC. These findings suggest that Aurora-B may
      be involved in tumor progression and that Aurora-B can be a new diagnostic and
      therapeutic target for OSCC.

PMID- 17235565
TI  - The expression of receptor for advanced glycation end products is associated with
      angiogenesis in human oral squamous cell carcinoma.
AB  - The receptor for advanced glycation end products (RAGE) is associated with cancer
      progression in several human cancers. In this study, we examined the roles of
      RAGE in the angiogenesis of oral squamous cell carcinoma (OSCC). RAGE
      concentration was examined in 20 OSCC tumors by enzyme-linked immunosorbent assay
      (ELISA). The microvessel density (MVD) and lymph vessel density (LVD) were
      examined by immunostaining. Concentrations of vascular endothelial growth factor
      (VEGF) and VEGF-C were examined in tumor tissues by ELISA. Tumoral RAGE
      concentration was associated with higher tumor MVD (P = 0.0123) and tumor VEGF
      concentration (P = 0.0344), but not with LVD and VEGF-C concentration. Treatment
      with RAGE ligand, high-mobility group box (HMGB)-1 increased the secretion of
      VEGF but not that of VEGF-C in human OSCC cell lines, HSC-3 and HSC-4. The effect
      of HMGB-1 was abrogated by RAGE down-regulation by antisense S-oligodeoxynucleic
      acid. These results suggest that RAGE expression is closely associated to
      angiogenesis in OSCC.

PMID- 17235566
TI  - Overexpression of laminin-5 gamma2 chain in clear cell carcinoma of the ovary.
AB  - One of the characteristic microscopic features of ovarian clear cell carcinoma
      (CCC) is the densely hyaline basement membrane material expanding the stroma. The
      biological significance of this material, however, has remained unclear. Recent
      studies have shown that laminin-5 (LN-5), a major component of the epithelial
      basement membrane, plays a more active role in cell migration or tumor invasion.
      In the present study, 20 CCCs and 5 borderline clear cell tumors were examined
      for LN-5 expression immunohistochemically, using an antibody against LN-5 gamma2
      chain. All of the 20 CCCs showed a focal or diffuse immunoreactivity with the LN
      5 gamma2 chain in the tumor stroma; whereas, borderline clear cell tumors rarely
      showed a stromal immunoreactivity. Cytoplasmic accumulation of the LN-5 gamma2
      chain was far less common than stromal accumulation, suggesting an accelerated
      secretion in CCC. In vitro, CCC cell lines showed a significant increase in cell
      migration over excessive LN-5, and the migration was blocked by an antibody
      against integrin alpha3. These results indicate that an interaction between CCC
      cells and extracellularly accumulated LN-5 is responsible for cell migration and
      the subsequent stromal invasion of CCC.

PMID- 17235567
TI  - Inhibition of estrogen-induced pituitary tumor growth and angiogenesis in Fischer
      344 rats by the matrix metalloproteinase inhibitor batimastat.
AB  - The development of estrogen-induced pituitary prolactinoma in Fischer 344 (F344)
      rats is associated with enhanced neovascularization. Based on the significance of
      matrix metalloproteinases (MMPs) for tumor growth and angiogenesis, we have
      studied the effect of batimastat (BB-94), a synthetic MMPs inhibitor (MMPI) on
      the progression of prolactin-secreting pituitary adenoma in rats. Pituitary
      tumors were induced in male F344 rats by s.c. implantation of Silastic tubes
      containing diethylstilbestrol (DES). The effects of chronic treatment with BB-94
      (30 mg/kg b.w.) on pituitary weight, cell proliferation, apoptosis and vascular
      density were evaluated. We have stated that chronic treatment with batimastat
      caused a significant reduction in the pituitary weight. Batimastat has been found
      to decrease cell proliferation evaluated by a number of PCNA-positive stained
      cell nuclei. A marked increase in the apoptotic index within the pituitary was
      observed in the study group. Moreover, the density of microvessels identified by
      CD31 was reduced in the group treated with BB-94. The results of our study
      provide evidence for an inhibitory effect of batimastat, a synthetic MMPI, on the
      growth and angiogenesis in an experimental model of human prolactinoma. The
      ability of BB-94 to suppress established pituitary tumor growth suggests a
      possible application of MMPIs in the treatment of pituitary adenomas.

PMID- 17235568
TI  - Expression of transcription factors and precursor cell markers during
      regeneration of beta cells in pancreata of rats treated with streptozotocin.
AB  - An understanding of beta cell regeneration is needed if we are to develop new
      treatment modalities in diabetes mellitus. Lineage tracing studies have shown
      that all pancreatic cell types, including beta cells, arise from PDX-1-expressing
      precursor cells. We studied beta cell regeneration by analyzing the
      immunocytochemical expression of the transcription factors, PDX-1, PBX-1, and
      MEIS2, and that of the potential precursor cell markers, c-Kit and nestin, using
      the model of streptozotocin (STZ)-induced diabetes in rats. The pancreata were
      examined 3, 7, and 14 days after STZ administration. PDX-1 expression, but not
      that of MEIS2 and PBX-1, transiently increased on day 7. c-Kit expression was
      found to be upregulated in islet cells at all points in time, while nestin
      expression was lacking. Ki-67 labeling was increased in islets on days 3 and 7.
      These results suggest that temporary upregulation of PDX-1 and prolonged
      overexpression of c-Kit may play a role during beta cell regeneration.

PMID- 17235570
TI  - Sertoli-Leydig cell tumours of the ovary and testis: a CGH and FISH study.
AB  - We present two malignant cases of Sertoli-Leydig cell tumours (SLCT) of the
      testis and one ovarian SLCT with benign behaviour. The DNA copy number changes
      affected chromosome 1, 8, 9p, 10, 11, 12, 16, 19, 22 and X. The present study is
      the first molecular-cytogenetic analysis of Sertoli-Leydig cell tumours of the
      testis.

PMID- 17235572
TI  - [Self-help for a rare, chronic disease].
AB  - The existence of support groups is of great interest, especially for individuals
      affected by a rare, chronic disease. The few affected people means a shortage of
      specialized physicians. As a result, affected individuals suffer from a great
      lack of information about their disease. Self-help organizations fill this gap
      and complement the work of physicians by informing patients, leading them through
      the health system and offering a partner to talk to. The support group "Society
      for von Hippel-Lindau (VHL) disease effected families" (Verein fur von der von
      Hippel-Lindau (VHL) Erkrankung betroffene Familien e.V.) puts its main emphasis
      on general information about the disease. In addition, the association supports
      the exchange of experience and helps to explain psychologically or socially
      determined problems associated with the VHL-disease. The foundation of ACHSE
      (Allianz Chronischer Seltener Erkrankungen, Alliance for Rare, Chronic
      Diseases)), as the parent organization for the German support groups for
      individuals affected by a rare disease, has been an important step towards
      communicating the specific needs of individuals affected by such diseases to the
      public.

PMID- 17235569
TI  - Extrauterine endometrial stromal sarcoma with JAZF1/JJAZ1 fusion confirmed by RT
      PCR and interphase FISH presenting as an inguinal tumor.
AB  - Endometrial stromal sarcomas are rare malignant mesenchymal tumors that usually
      develop in the uterine corpus and occasionally arise at various extrauterine
      sites. This report describes the first case of primary extrauterine endometrial
      stromal sarcoma arising in the extraperitoneal portion of the round ligament
      presenting as a solitary inguinal mass in a 46-year-old woman. The patient
      presented gradually growing tumor in the right inguinal region. Local tumor
      resection was performed and no recurrence or metastasis was found at 15 months
      after the operation. Histological examination revealed that the tumor comprised
      uniform, spindle-shaped cells with blunt nuclear figure and scattered small
      arteries, and infiltrated into adjacent tissue. No endometriosis was
      morphologically identified in the lesion. Immunohistochemically, the tumor cells
      were positive for CD10, estrogen receptor, progesterone receptor, alpha-smooth
      muscle actin, and calponin. We confirmed JAZF1/JJAZ1 fusion by reverse
      transcription-polymerase chain reaction and the corresponding chromosomal
      translocation by interphase fluorescence in situ hybridization on paraffin
      sections. It is essential that the inguinal region should be recognized as a
      possible primary site of endometrial stromal sarcoma, and the detection of a
      JAZF1/JJAZ1 fusion can be useful when the diagnosis is not confirmed by
      microscopic observation or immunohistochemistry for the tumor arising in
      extrauterine sites.

PMID- 17235574
TI  - [Oxygen therapy in a COPD-patient under nCPAP therapy].

PMID- 17235573
TI  - [Von Hippel-Lindau disease. Interdisciplinary patient care].
AB  - Von Hippel-Lindau disease is an important hereditary tumor syndrome with a clear
      option for effective treatment if diagnosed in time. Interdisciplinary
      cooperation is the key to successful management. Major components of the disease
      are retinal capillary hemangioblastomas, hemangioblastomas of cerebellum, brain
      stem and spine, renal clear cell carcinomas, pheochromocytomas, multiple
      pancreatic cysts and islet cell carcinomas, tumors of the endolymphatic sac of
      the inner ear, and cystadenomas of the epididymis and broad ligament. A well
      structured screening program should be performed at yearly intervals.

PMID- 17235575
TI  - Intraosseous pilomatricoma: a possible rare skeletal manifestation of Gardner
      syndrome.
AB  - Here we report a case of intraosseous pilomatricoma in a patient with Gardner
      syndrome. A 17-year-old boy with a family history of Gardner syndrome and
      multiple cutaneous epidermoid cysts presented with pain in the region below the
      knee of the left leg. Plain radiographs displayed a well-circumscribed eccentric
      lesion of mixed radiolucent and radiopaque density within the diaphysis of the
      left proximal tibia. By magnetic resonance (MR) imaging, the lesion appeared as a
      low intensity lesion in T1-weighted images and a heterogeneous high intensity
      lesion with a low-signal radiation pattern on T2-weighted images. Gadolinium
      enhancement was observed partially within the lesion and intensely in the lesion
      rim. After curettage, histological examination revealed a massive accumulation of
      keratinous material with epithelial nests that displayed both epidermal and
      trichilemmal keratinization with basaloid and shadow cells and with metaplastic
      ossification. These features confirmed a pathological diagnosis of intraosseous
      counterpart of pilomatricoma. In the context of this patient's skin lesions,
      intraosseous pilomatricoma may be a rare skeletal manifestation of Gardner
      syndrome.

PMID- 17235576
TI  - Nerves in bone: the silent partners.

PMID- 17235577
TI  - A case report of Wyburn-Mason syndrome and review of the literature.
AB  - INTRODUCTION: Wyburn-Mason syndrome is a distinct congenital neurocutaneous
      entity comprised of ipsilateral arteriovenous malformations (AVMs) of the
      midbrain, vascular abnormalities affecting the visual pathway, and facial nevi.
      METHODS: We report a case and review of the literature of all other reported
      cases of Wyburn-Mason syndrome (n = 26) in the English literature since 1973.
      RESULTS: In this review, we report on a 4(1/2)-year-old boy with Wyburn-Mason
      syndrome who presented with left retinal and orbital AVMs and a ruptured thalamic
      AVM. The patient did not respond to light in the left eye and demonstrated a left
      afferent pupillary defect. He did not have any cutaneous lesions. We also
      characterize other reported cases of Wyburn-Mason syndrome. CONCLUSION: The
      presentation of patients with Wyburn-Mason syndrome can vary greatly according to
      the site and the extent of vascular lesions. Intracranial AVMs occasionally
      hemorrhage with significant morbidity. Treatment is controversial, and patients
      are typically managed conservatively by observation.

PMID- 17235578
TI  - Effects of temperature on pacemaker potentials in the mouse small intestine.
AB  - The effects of temperature on the generation of pacemaker potentials recorded
      from myenteric interstitial cells of Cajal (ICC-MY) distributed in the mouse
      small intestine were investigated using intracellular recording techniques. In
      response to increasing temperatures in the range of 26-40 degrees C, the
      frequency and maximum rate of rise (dV/dt (max)) of pacemaker potentials were
      increased while their duration was decreased. The resting membrane potential and
      amplitude of the pacemaker potentials were not affected by change in temperature.
      Elevation of temperature decreased the amplitude, duration, and rise time of
      unitary potentials generated spontaneously during intervals between the pacemaker
      potentials. Metabolic inhibition (KCN and iodoacetic acid) decreased the
      frequency of pacemaker potentials with no alteration to the amplitude and dV/dt
      (max). Cyclopiazonic acid (3 muM), an inhibitor of the internal Ca(2+) pump,
      abolished pacemaker potentials in low-temperature conditions (<29 degrees C) but
      not at high-temperature conditions (>38 degrees C). These results suggest that
      the primary and plateau components of pacemaker potentials have different
      temperature sensitivities: the primary component is highly temperature-sensitive
      and is activated at higher temperatures, while the plateau component is formed by
      activation of temperature-insensitive mechanisms. The results also suggest that
      the mitochondria-induced intracellular Ca(2+) handling system seems to be
      involved in the initiation of the generation of pacemaker potentials but not in
      their configuration.

PMID- 17235579
TI  - Insomnia symptoms and their correlates among the elderly in geriatric homes in
      Alexandria, Egypt.
AB  - The prevalence of sleep complaints increases steadily with age. Studies
      investigating insomnia among elderly people living in geriatric homes, especially
      among Egyptians, are scarce. This study aimed to determine the prevalence of
      insomnia symptoms among the elderly living in geriatric homes in Alexandria and
      their correlates. A cross-sectional survey of a representative sample of elderly
      population of geriatric homes in Alexandria was implemented. A total of 177
      persons aged 60 years or older participated. Difficulty initiating sleep was
      reported by 65% of the participants. Approximately half of them had difficulty
      maintaining their sleep (50.8%) or had non-restful sleep (51.4%). Short sleep was
      reported by 43.5% of the participants, while early morning awakening was reported
      by 28.2%. Advanced age (> or = 75 years) was significantly associated with
      increased risk for early morning awakening, non-restful sleep and short sleep.
      Women had approximately a fourfold risk of non-restful sleep as opposed to men.
      Short stay in geriatric homes (<1 year) was associated with 2.5-fold increased
      risk of non-restful sleep. Unmarried status was strongly and positively related
      to difficulty to maintain sleep and non-restful sleep. Depressive status was
      significantly associated with an increased risk of difficulty to maintain sleep
      and decreased risk of early morning awakening. Conclusively, the present study
      showed that insomnia symptoms are highly prevalent among the elderly living in
      geriatric homes. It also revealed that although age, gender, and other socio
      demographic factors are correlated with insomnia symptoms, other factors are
      highly important. Health care providers should take these factors in
      consideration when dealing with elderly patients who complain of insomnia.

PMID- 17235580
TI  - In-home evaluation of efficacy and titration of a mandibular advancement device
      for obstructive sleep apnea.
AB  - There is increasing evidence that mandibular advancement devices (MADs) can be an
      effective treatment for some patients with obstructive sleep apnea, a highly
      prevalent chronic disease. In this study, the objectives were to objectively
      assess the effectiveness of MAD therapy using a limited channel recorder, and to
      develop a model for identifying patients who may be appropriate for MAD therapy
      as the initial treatment option. Thirty patients were prospectively recruited and
      studied at two independent dentist offices and the participants' homes. Subjects
      wore the ARES Unicorder for two nights before insertion of the MAD, and again
      when the dentist determined that the patient had reached the titration endpoint.
      Self-reported measures of depression, sleepiness, and quality of life were
      obtained pre- and posttreatment. The reviewer was blinded to the study status
      while the physiological signals were being visually inspected. Significant
      reductions in the apnea/hypopnea index (AHI), hypoxemia measures, and snoring
      level were observed posttreatment. Twenty-seven of the 30 (90%) patients had a
      posttreatment AHI (using a 4% desaturation for hypopneas) below a clinical cut
      off of 10. All but one patient (97%) exhibited at least a 50% decrease in AHI or
      had a posttreatment AHI < or = 10. Significant differences in body mass index,
      weight, and neck circumference in patients with posttreatment AHIs above and
      below a clinical cut-off of five were identified. The linear regression used to
      predict the posttreatment AHI using pretreatment data resulted in an R(2) of
      0.68. The model correctly predicted two patients who were unable to obtain a
      posttreatment AHI of 10 or less. This study was designed to demonstrate two
      models of collaboration between a dental sleep medicine specialist and a sleep
      medicine physician in the monitoring of a patient treated with a MAD. The outcome
      data suggest that the limited channel recording system can be used as an
      alternative to laboratory polysomnography to reduce the cost of MAD treatment,
      and to improve the quality and consistency of posttreatment patient care.

PMID- 17235581
TI  - Dispersion relation in oscillatory reaction-diffusion systems with self
      consistent flow in true slime mold.
AB  - In the large amoeboid organism Physarum, biochemical oscillators are spatially
      distributed throughout the organism and their collective motion exhibits phase
      waves, which carry physiological signals. The basic nature of this wave behaviour
      is not well-understood because, to date, an important effect has been neglected,
      namely, the shuttle streaming of protoplasm which accompanies the biochemical
      rhythms. Here we study the effects of self-consistent flow on the wave behaviour
      of oscillatory reaction-diffusion models proposed for the Physarum plasmodium, by
      means of numerical simulation for the dispersion relation and weakly nonlinear
      analysis for derivation of the phase equation. We conclude that the flow term is
      able to increase the speed of phase waves (similar to elongation of wave length).
      We compare the theoretical consequences with real waves observed in the organism
      and also point out the physiological roles of these effects on control mechanisms
      of intracellular communication.

PMID- 17235582
TI  - Wild-type CYP102A1 as a biocatalyst: turnover of drugs usually metabolised by
      human liver enzymes.
AB  - This work provides functional data showing that the bacterial CYP102A1 recognises
      compounds metabolised by human CYP3A4, CYP2E1 and CYP1A2 and is able to catalyse
      different reactions. Wild-type cytochrome CYP102A1 from Bacillus megaterium is a
      catalytically self-sufficient enzyme, containing an NADPH-dependent reductase and
      a P450 haem domain fused in a single polypeptidie chain. An NADPH-dependent
      method (Tsotsou et al. in Biosens. Bioelectron. 17:119-131, 2002) together with
      spectroscopic assays were applied to investigate the catalytic activity of
      CYP102A1 towards 19 xenobiotics, including 17 commercial drugs. These molecules
      were chosen to represent typical substrates of the five main families of drug
      metabolising human cytochromes P450. Liquid chromatography-mass spectrometry
      analysis showed that CYP102A1 catalyses the hydroxylation of chlorzoxazone,
      aniline and p-nitrophenol, as well as the N-dealkylation of propranolol and the
      dehydrogenation of nifedipine. These drugs are typical substrates of human CYP2E1
      and CYP3A4. The KM values calculated for these compounds were in the millimolar
      range: 1.21+/-0.07 mM for chlorzoxazone, 2.52 +/- 0.08 mM for aniline, 0.81+/
      0.04 mM for propranolol. The values of vmax for chlorzoxazone and propranolol
      were 46.0+/-9.0 and 7.6+/-3.4 nmol min-1 nmol-1, respectively. These values are
      higher then those measured for the human enzymes. The vmax value for aniline was
      9.4+/-1.3 nmol min-1 nmol-1, comparable to that calculated for human cytochromes
      P450. The functional data were found to be in line with the sequence alignments,
      showing that the identity percentage of CYP102A1 with CYP3A4 and CYP2E1 is higher
      than that found for CYP1A2, CYP2C9 and CYP2D6 families.

PMID- 17235583
TI  - A giant pancreatic serous microcystic adenoma with 20 years follow-up.
AB  - BACKGROUND AND AIMS: There is only little information about the spontaneous
      course of large pancreatic serous tumours. We followed up a white woman with a
      giant serous microcystic adenoma over more than 20 years. CASE REPORT: At first
      clinical presentation, in 1986, the tumour measured 4.5 cm in diameter. Two years
      later, it measured 6 cm and was considered as non-resectable at laparotomy. A
      biopsy was obtained, and the tumour was diagnosed as lymphangioma, based on
      hematoxylin and eosin-staining. During the follow-up, the tumour progressively
      increased in size, measuring 12 cm in diameter in 1993 and 17 cm in 2000. Thus,
      an average growth rate of 0.83 cm per year was calculated. Unspecific abdominal
      discomfort and pain were the leading clinical symptoms. A colonic resection was
      necessary because of compression by the tumour in 1993. Portal hypertension was
      detected at laparotomy. Finally, the initial biopsy specimen was re-evaluated,
      using immunohistochemistry, and the final diagnosis of a serous microcystic
      adenoma was made. CONCLUSION: This unique case demonstrates that the spontaneous
      course of serous microcystic adenoma of the pancreas may be favourable even with
      huge tumour size and that immunohistochemistry may prove a valuable tool for
      differential diagnosis of cystic pancreatic lesions. Due to their size and
      progressive, space-occupying growth, these biologically benign tumours may cause
      injury to adjacent organs and thus clinical symptoms. For this reason, curative
      surgical resection is the treatment of choice for this tumour entity except for
      small, asymptomatic lesions, which do not require intervention. When radical
      resection is impossible, palliative surgery may improve the quality of life for
      several years. The risk of malignant transformation seems to be low even in the
      long-term course.

PMID- 17235584
TI  - Radical lymph node resection of the retroperitoneal area for left-sided colon
      cancer.
AB  - BACKGROUND/AIMS: Radical lymph node resection of the retroperitoneal area for
      cancer of the left half of the colon has been strongly questioned. The purpose of
      the study was to investigate the effect of extended lymph node resection of the
      retroperitoneal area in left-sided colon cancer. MATERIALS AND METHODS: From 1993
      to 2002, 124 patients with left-sided colon cancer were randomly elected to
      undergo either conventional left colectomy (62 patients) or left colectomy
      combined with radical lymphadenectomy (62 patients). Clinical features were
      correlated to survival, recurrences, hospital mortality, morbidity, and late
      urogenital morbidity. Survival was the end point of the study. RESULTS: The
      groups were comparable for age, gender, physical status, TNM stage, tumor
      distribution, degree of differentiation, postoperative complications,
      chemotherapy, recurrences, sites of recurrence, and late urogenital morbidity (p
      > 0.05). Hospital mortality was higher in conventional surgery group (p = 0.008).
      Survival rates of 5 and 10 years did not differ significantly between the two
      groups (p > 0.05), although there was a trend of improvement after radical
      lymphadenectomy. Stage III patients in radical lymphadenectomy group had
      significantly better survival over those in the conventional surgery group (p =
      0.0406). CONCLUSIONS: Radical lymph node resection of the retroperitoneal area is
      associated with the same rate of hospital morbidity, late urogenital morbidity,
      and total survival as is conventional surgery. It seems that there is a trend for
      improvement of survival particularly in stage III patients.

PMID- 17235585
TI  - Alleviation of ischemia-reperfusion injury in rat liver transplantation by
      induction of small interference RNA targeting Fas.
AB  - BACKGROUND: Cellular apoptosis plays an important role in ischemia-reperfusion
      (I/R) injury during organ transplantation. Synthetic small interference RNA
      (siRNA) targeting apoptotic receptor Fas has proven effective to protect mice
      against hepatitis and renal I/R injury. The objective of this study is to
      investigate the silencing impact of Fas siRNA to alleviate I/R injury in rat
      liver transplantation. MATERIALS AND METHODS: Rat hepatocytes (BRL cells) were
      transfected with three pairs of synthesized Fas siRNA; cells untreated and
      treated with GFP siRNA were taken as blank and siRNA control. The most effective
      Fas siRNA was chosen for in vivo experiments. Syngeneic orthotopic liver
      transplantation was performed in Fas siRNA group, siRNA control group, and blank
      control group of Sprague-Dawley rats. There were 25 pairs of rats in each group.
      siRNA transfection of donor rats was done with hydrodynamic injection method 48 h
      before liver procurement. Blood and liver samples were collected for evaluation
      of serum ALT levels, Fas protein and mRNA expression, and apoptosis by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, 1,
      3, 6, 12, and 24 h after liver transplantation. RESULTS: Fas siRNA2, which
      inhibited Fas gene expression much more than other siRNAs, was chosen for in vivo
      experiment. The serum ALT levels of Fas siRNA group were much less than those of
      blank and siRNA control groups 1, 3, 6, 12, and 24 h after blood reperfusion,
      indicating diminishing ischemia-reperfusion injury. Donor livers in Fas siRNA
      group had substantially less cell apoptosis. The expression of Fas mRNA and
      protein was reduced dramatically in the Fas siRNA group compared with the other
      two groups. CONCLUSION: Fas-mediated apoptosis play an important role in I/R
      injury of rat liver transplantation. Silencing Fas by hydrodynamic injection of
      siRNA holds therapeutic promise to limit I/R injury.

PMID- 17235586
TI  - Systemic immune dysfunction in pancreatic cancer patients.
AB  - BACKGROUND AND AIMS: We investigated the immune status in 32 pancreatic cancer
      patients (PC) in comparison with healthy controls (HC). MATERIALS AND METHODS:
      Using flow cytometry, peripheral blood lymphocytes (PBL) were characterized by
      the expression of surface markers for T helper cells (CD4), T suppressor cells
      (CD8), B cells (CD19) and NK cells (CD56). The blastogenic response of PBL was
      analyzed after stimulation with concavalin A (ConA), phytohemagglutinin (PHA),
      pokeweed mitogen (PWM) and anti-CD3 antibodies. The serum levels of TNF-alpha, IL
      1beta, IL-2, IL-10, IL-12, IL-18, IL-1RA, sIL-2R and TGF-beta were determined by
      ELISA. RESULTS: No differences in the distribution of peripheral immunocytes in
      PC were found, whereas the blastogenic response of peripheral blood lymphocytes
      (PBL) after stimulation with PHA or anti-CD3 antibodies was significantly
      decreased in PC. In PC, we found reduced serum levels of IL-2 and significantly
      elevated levels of TNF-alpha, TGF-beta1, IL-10, IL-2R, IL-1beta and IL-1RA.
      CONCLUSION: These data provide evidence for a systemic immune dysfunction in
      pancreatic cancer patients characterized by a shift towards a T helper cell type
      2 cytokine profile, a significant elevation of substances related to T cell
      suppression and a reduced blastogenic response to PHA and anti-CD3 antibodies of
      PBL.

PMID- 17235587
TI  - The axillary access in unilateral thyroid resection.
AB  - BACKGROUND AND STUDY AIMS: With this study, we intended to find out if it is
      possible to avoid the typical scar after thyroid resection by using a 20 mm
      axillary access and a 3.5 mm incision in the jugulum. MATERIALS AND METHODS: We
      present the results of our proof-of-concept study with 12 patients. For this
      technique, a modified axilloscope and ultrasonic scissors were used, which permit
      a total resection of the unilateral thyroid. RESULTS: The feasibility of this
      endoscopic technique was shown by the successful operation of these patients with
      unilateral pathological findings. Furthermore, we showed that this technique
      allows to resect tissue up to a whole lobe while at the same time finding and
      identifying the recurrent laryngeal nerve and subsequently verifying the findings
      by using the neuro-monitoring system. CONCLUSIONS: This study shows that
      endoscopic thyroid surgery approximates the norms of endocrine neck surgery. The
      presented method is useful in thyroid surgery for patients with single nodules
      and a small thyroid gland.

PMID- 17235588
TI  - Early outcomes of surgery for small bowel obstruction: analysis of risk factors.
AB  - OBJECTIVES: The study aimed to review the etiologies of patients who underwent
      surgery for small bowel obstruction (SBO) and to evaluate the risk factors
      affecting the early postoperative outcomes. MATERIALS AND METHODS: A case series
      of 430 patients (252 men) with a mean age of 64.5 years, who underwent 437
      operations for SBO, were retrospectively reviewed. RESULTS: Peritoneal adhesions
      and hernia were the most common causes of SBO, contributing 42.3 and 26.8% of all
      cases, respectively. Strangulation occurred in 27.7% and caused nonviable bowel
      in 13.0% of obstructing episodes. Old age (age >/= 70 years), female patient,
      nonadhesive obstruction, and hernia were the independent significant factors
      associated with bowel strangulation. The 30-day mortality was 6.5%, and the
      median postoperative hospital stay was 8 days. Old age, the presence of premorbid
      pulmonary disease, and malignant obstruction were the independent factors
      associated with operative mortality. The overall complication rate was 35.5%, and
      old age was the only significant factor associated with postoperative
      complications. CONCLUSIONS: Surgery for SBO is still associated with significant
      mortality and morbidity. As old age is significantly associated with an increased
      incidence of strangulation, operative mortality, and complications, this group of
      patients should be managed with extra cautions to avoid unfavorable outcome of
      surgery.

PMID- 17235590
TI  - [100 years of the Institute for Pathology and Cytology at the Municiapl Hospitals
      Wiesbaden].

PMID- 17235589
TI  - Adrenal involvement in multiple endocrine neoplasia type 1: results of 7 years
      prospective screening.
AB  - BACKGROUND: Adrenal tumors are a common manifestation of the multiple endocrine
      neoplasia type 1 (MEN-1) syndrome. Prevalence in recent studies varies between 9
      and 45%. A genotype-phenotype correlation has been described as well as the
      development of adrenocortical carcinomas. Long-term prospective data are still
      lacking. MATERIALS AND METHODS: Thirty-eight MEN-1 patients with proven germline
      mutations have been prospectively observed in a regular screening program in our
      hospital. Adrenal glands have been screened by biochemical analysis and either by
      endoscopic ultrasound (EUS) or computed tomography (CT) or both. Median follow-up
      was 48 months (12-108 months). Age at diagnosis of MEN-1, type of adrenal tumor,
      genotype, therapy, and clinical characteristics have been analyzed. RESULTS: In
      21 (55%) patients, adrenal involvement of the disease was detected. Adrenal
      lesions were detected in average 6.9 years after the initial diagnosis of MEN-1.
      Median tumor size was 12 mm (5-40 mm). Tumor size smaller than 10 mm was observed
      in 11 patients. Twelve patients had unilateral while nine had bilateral adrenal
      lesions. EUS detected all adrenal tumors, whereas CT failed in seven cases. In
      three patients, functioning tumors (one pheochromocytoma, one bilateral Cushing
      adenoma, and one adrenocortical carcinoma) and one nonfunctioning adenoma were
      diagnosed by histology and biochemical assessment. Two laparoscopic
      adrenalectomies and one laparoscopic subtotal resection were performed.
      Nonfunctioning adrenal lesions, not characterized by histology yet, were found in
      18 patients. There was no statistical difference with regard to adrenal
      involvement between patients with germline mutations in exons 2 and 10 (12/21)
      and those with mutations in exons 3-9 (6/11). CONCLUSION: MEN-1-associated
      adrenal tumors are mostly small, benign, and nonfunctioning and much more common
      than previously reported. EUS was the most sensitive imaging procedure. The
      genotype-pheotype correlation previously suggested by our group could not be
      confirmed.

PMID- 17235591
TI  - Festschrift to recognize the contribution of Klaus Arnold to the field of
      biophysics on the occasion of his 65th birthday.

PMID- 17235592
TI  - Posttraumatic intratumoural haemorrhage: an unusual presentation of spinal
      ependymoma.
AB  - Ependymomas presenting with intratumoural and/or subarachnoid haemorrhages are
      seen rarely. These haemorrhages are mostly due to anticoagulation, epidural
      analgesia or pregnancy. A 62-year-old male farmer with cauda equina syndrome
      after a work-related trauma is presented. He was admitted to our hospital with
      paraparesis, faecal incontinence and sensory loss below the level of the lumbar-2
      dermatome. Magnetic resonance imaging of the spine displayed an intradural mass
      lesion at the level of the first lumbar vertebrae. The lesion was excised totally
      via dorsal midline approach. Histopathologic examination revealed grade-3
      ependymoma with intratumoural haemorrhage. The patient's symptoms were relieved
      completely on postoperative day 7. The patient was given information about
      periodical examination for recurrence and discharged on the third postoperative
      week. Asymptomatic spinal lesions should be considered for operation whenever
      detected because of unpredicted complications.

PMID- 17235594
TI  - Abscess formation as a complication of a ruptured urachal cyst.
AB  - The urachus is a midline tubular structure that extends upward from the dome of
      the bladder toward the umbilicus. This tubular structure normally involutes
      before birth, remaining as a fibrous band with no known function. Persistence of
      all or any portion of the fetal urachus results in several anomalies, the most
      common of which is the urachal cyst (Yu JS, Kim KW, Lee HJ, Lee YJ, Yoon CS, Kim
      MJ, Radiographics, 21:451-4611, 2001; Ohgaki M, Higuchi A, Chou H, Takashina K,
      Kawakami S, Fujita Y, Hagiwara A, Yamagishi H, Surg Today, 33:75-77, 2003).
      Although most urachal cysts are asymptomatic, there are a few reports about
      intraperitoneal rupture of infected urachal cysts, all of which caused
      peritonitis and sepsis (Ohgaki M, Higuchi A, Chou H, Takashina K, Kawakami S,
      Fujita Y, Hagiwara A, Yamagishi H, Surg Today, 33:75-77, 2003; Kojima Y, Miyake
      O, Taniwaki H, Morimoto A, Takahashi S, Fujiwara I, Int J Urol, 10:174-176, 2003;
      Agatstein EH, Stabile BE, Arch Surg, 119:1269-1273, 1984). We report the imaging
      and operative findings of a patient, presented with a urachal abscess after a
      spontaneously ruptured urachal cyst.

PMID- 17235595
TI  - Intermittent small bowel obstruction with retained endoscopic capsule: MDCT and
      plain radiographic appearance.

PMID- 17235596
TI  - Bee-hawking by the wasp, Vespa velutina, on the honeybees Apis cerana and A.
      mellifera.
AB  - The vespine wasps, Vespa velutina, specialise in hawking honeybee foragers
      returning to their nests. We studied their behaviour in China using native Apis
      cerana and introduced A. mellifera colonies. When the wasps are hawking, A.
      cerana recruits threefold more guard bees to stave off predation than A.
      mellifera. The former also utilises wing shimmering as a visual pattern
      disruption mechanism, which is not shown by A. mellifera. A. cerana foragers
      halve the time of normal flight needed to dart into the nest entrance, while A.
      mellifera actually slows down in sashaying flight manoeuvres. V. velutina
      preferentially hawks A. mellifera foragers when both A. mellifera and A. cerana
      occur in the same apiary. The pace of wasp-hawking was highest in mid-summer but
      the frequency of hawking wasps was three times higher at A. mellifera colonies
      than at the A. cerana colonies. The wasps were taking A. mellifera foragers at a
      frequency eightfold greater than A. cerana foragers. The final hawking success
      rates of the wasps were about three times higher for A. mellifera foragers than
      for A. cerana. The relative success of native A. cerana over European A.
      mellifera in thwarting predation by the wasp V. velutina is interpreted as the
      result of co-evolution between the Asian wasp and honeybee, respectively.

PMID- 17235597
TI  - Brain modulation of Dufour's gland ester biosynthesis in vitro in the honeybee
      (Apis mellifera).
AB  - Caste-specific pheromone biosynthesis is a prerequisite for reproductive skew in
      the honeybee. Nonetheless, this process is not hardwired but plastic, in that egg
      laying workers produce a queen-like pheromone. Studies with Dufour's gland
      pheromone revealed that, in vivo, workers' gland biosynthesis matches the social
      status of the worker, i.e., sterile workers showed a worker-like pattern whereas
      fertile workers showed a queen-like pattern (production of the queen-specific
      esters). However, when incubated in vitro, the gland spontaneously exhibits the
      queen-like pattern, irrespective of its original worker type, prompting the
      notion that ester production in workers is under inhibitory control that is queen
      dependent. We tested this hypothesis by exposing queen or worker Dufour's glands
      in vitro to brain extracts of queens, queenright (sterile) workers and males.
      Unexpectedly, worker brain extracts activated the queen-like esters biosynthesis
      in workers' Dufour's gland. This stimulation was gender-specific; queen or worker
      brains demonstrated a stimulatory activity, but male brains did not. Queen gland
      could not be further stimulated. Bioassays with heated and filtered extracts
      indicate that the stimulatory brain factor is below 3,000 Da. We suggest that
      pheromone production in Dufour's gland is under dual, negative-positive control.
      Under queenright conditions, the inhibitor is released and blocks ester
      biosynthesis, whereas under queenless conditions, the activator is released,
      activating ester biosynthesis in the gland. This is consistent with the
      hypothesis that queenright workers are unequivocally recognized as non-fertile,
      whereas queenless workers try to become "false queens" as part of the
      reproductive competition.

PMID- 17235599
TI  - Spontaneous resolution of a full thickness idiopathic macular hole: fundus
      autofluorescence and OCT imaging.
AB  - BACKGROUND: To report on the spontaneous closure of a full thickness
      juxtafoveolar idiopathic macular hole (IMH) monitored with fundus
      autofluorescence (AF) as well as optical coherence tomography (OCT) imaging.
      METHODS: Observational case report. Fundus Autofluorescence with a confocal SLO
      (HRA, Heidelberg Engineering, Germany) and OCT imaging were used to monitor the
      spontaneous evolution of a stage II IMH. RESULTS: A 70 year-old woman with
      unremarkable ocular history received a diagnosis of idiopathic macular hole in
      the left eye. Bright autofluorescence corresponding to the IMH was documented
      with the confocal SLO and OCT imaging could confirm the presence of an hour glass
      shaped full thickness juxtafoveolar IMH. Biomicroscopy revealed no posterior
      vitreous detachment (PVD). Few months later clinical examination demonstrated the
      presence of typical symptoms and signs of PVD (miodesopsias and Weiss ring). The
      bright autofluorescence corresponding to the IMH disappeared and OCT imaging
      documented a normal fovea in morphology and thickness. CONCLUSIONS: Spontaneous
      closure of full thickness juxtafoveolar IMH can occur and may be properly
      monitored with fundus AF as well as OCT imaging.

PMID- 17235598
TI  - Getting ready for the manned mission to Mars: the astronauts' risk from space
      radiation.
AB  - Space programmes are shifting towards planetary exploration and, in particular,
      towards missions by human beings to the Moon and to Mars. Radiation is considered
      to be one of the major hazards for personnel in space and has emerged as the most
      critical issue to be resolved for long-term missions both orbital and
      interplanetary. The two cosmic sources of radiation that could impact a mission
      outside the Earth's magnetic field are solar particle events (SPE) and galactic
      cosmic rays (GCR). Exposure to the types of ionizing radiation encountered during
      space travel may cause a number of health-related problems, but the primary
      concern is related to the increased risk of cancer induction in astronauts.
      Predictions of cancer risk and acceptable radiation exposure in space are
      extrapolated from minimal data and are subject to many uncertainties. The paper
      describes present-day estimates of equivalent doses from GCR and solar cosmic
      radiation behind various shields and radiation risks for astronauts on a mission
      to Mars.

PMID- 17235600
TI  - Hans goldmann: the legacy of a giant.

PMID- 17235601
TI  - Abnormal recruitment of periendothelial cells to lymphatic capillaries in
      digestive organs of angiopoietin-2-deficient mice.
AB  - The fine structure of lymphatic capillaries in the digestive organs of
      angiopoietin-2 (Ang2) knockout mice was studied by using both
      immunohistochemistry and electron microscopy. The genetic deletion of Ang2
      yielded hypoplasia and disorganization of the lymphatic capillaries, with their
      shapes being irregular, and an aberrant recruitment of vascular periendothelial
      cells immunopositive for smooth muscle actin to the lymphatic capillaries. The
      abnormal lymphatic periendothelial cells were considered to be a type of pericyte
      for the lymphatic capillaries after the deletion of Ang2, because they were
      ultrastructurally characterized by abundant thin myofilaments in their cytoplasm
      and long cytoplasmic extensions similar to those shown by blood vascular
      pericytes. The genetic replacement of Ang2 with Ang1 rescued the defects, viz.,
      the disorganization and disordered structure of the lymphatic capillaries. The
      present findings suggest that Ang2 serves the morphogenesis of lymphatic
      capillaries as an agonist for the receptor, Tie2, and that Ang1 can replace Ang2
      in guiding lymphatic formation and development.

PMID- 17235603
TI  - Transformational and derivational strategies in analogical problem solving.
AB  - Analogical problem solving is mostly described as transfer of a source solution
      to a target problem based on the structural correspondences (mapping) between
      source and target. Derivational analogy (Carbonell, Machine learning: an
      artificial intelligence approach Los Altos. Morgan Kaufmann, 1986) proposes an
      alternative view: a target problem is solved by replaying a remembered problem
      solving episode. Thus, the experience with the source problem is used to guide
      the search for the target solution by applying the same solution technique rather
      than by transferring the complete solution. We report an empirical study using
      the path finding problems presented in Novick and Hmelo (J Exp Psychol Learn Mem
      Cogn 20:1296-1321, 1994) as material. We show that both transformational and
      derivational analogy are problem-solving strategies realized by human problem
      solvers. Which strategy is evoked in a given problem-solving context depends on
      the constraints guiding object-to-object mapping between source and target
      problem. Specifically, if constraints facilitating mapping are available,
      subjects are more likely to employ a transformational strategy, otherwise they
      are more likely to use a derivational strategy.

PMID- 17235604
TI  - An incidental finding of unicornuate uterus with unilateral ovarian agenesis
      during cesarean delivery.
AB  - INTRODUCTION: The association of mullerian anomalies with concomitant gonadal
      development abnormalities is very rare. The literature revealed only a few cases
      of unicornuate uterus with unilateral ovarian agenesis. The pathophysiology of
      this rare combination is not clear. CASE REPORT: A 31-year-old primiparous woman
      at 38 weeks' gestation admitted to our labor room due to painful uterine
      contractions. An emergency cesarean section was performed and a 3,100-g healthy
      male infant was delivered. At cesarean delivery, she was found to have
      unicornuate uterus with no evidence of a rudimentary horn and the absence of a
      left (unilateral) ovary. The right fallopian tube, round ligament, and ovary were
      all normal. The left fallopian tube, round ligament, and ovary were all absent.
      Intraabdominal exploration, intravenous pyelography, postoperative abdominal and
      transvaginal ultrasonography were failed to reveal additional gynecologic, renal
      and urinary tract anomalies. CONCLUSION: To our best knowledge this case is
      unique since the incidental diagnosis of unicornuate uterus with ipsilateral
      ovary was made during cesarean delivery.

PMID- 17235602
TI  - Distribution and characterization of nitric oxide synthase in the nervous system
      of Triatoma infestans (Insecta: Heteroptera).
AB  - The biochemical characterization of nitric oxide synthase (NOS) and its
      distribution in the central nervous system (CNS) were studied in the heteropteran
      bug Triatoma infestans. NOS-like immunoreactivity was found in the brain,
      subesophageal ganglion, and thoracic ganglia by using immunocytochemistry. In the
      protocerebrum, NOS-immunoreactive (IR) somata were detected in the anterior,
      lateral, and posterior soma rinds. In the optic lobe, numerous immunostained
      somata were observed at the level of the first optic chiasma, around the lobula,
      and in the proximal optic lobe. In the deutocerebrum, NOS-IR perikarya were
      mainly observed in the lateral soma rind, surrounding the sensory glomeruli, and
      a few cell bodies were seen in association with the antennal mechanosensory and
      motor neuropil. No immunostaining could be detected in the antennal nerve. The
      subesophageal and prothoracic ganglia contained scattered immunostained cell
      bodies. NOS-IR somata were present in all the neuromeres of the posterior
      ganglion. Western blotting showed that a universal NOS antiserum recognized a
      band at 134 kDa, in agreement with the expected molecular weight of the protein.
      Analysis of the kinetics of nitric oxide production revealed a fully active
      enzyme in tissue samples of the CNS of T. infestans.

PMID- 17235605
TI  - Ranking bioprocess variables using global sensitivity analysis: a case study in
      centrifugation.
AB  - The selection of appropriate operating conditions for bioprocessing is complex
      due to the large number of interacting stages and variables. Bioprocesses also
      operate under tight regulation and therefore tools to assist bioprocess design
      are of significant utility. Conventional approaches for the analysis of variable
      sensitivities are inadequate. We propose the use of global sensitivity analysis
      to determine the level of importance of each variable and their interactions.
      Once key variables have been determined, the designer may focus on the most
      significant subset. Two case studies are used to demonstrate the applicability of
      the approach. Each is based on centrifugation and determines the impact of flow
      rate, feed viscosity, density difference and particle size, while performance is
      assessed by supernatant clarification. Significant differences in sensitivities
      were found between the two studies due to the different feed material properties.
      Variable sensitivities were found to be system-specific and provide insight for
      potential operating strategies.

PMID- 17235606
TI  - Use of local cues in the night-time navigation of the wandering desert spider
      Leucorchestris arenicola (Araneae, Sparassidae).
AB  - Adult male Leucorchestris arenicola can walk round-trips of several tens of
      meters in search of females. Most excursions end with the spiders returning to
      their burrow. For small animals homing over distances of several meters is
      theoretically impossible without the aid of external cues. It was investigated,
      whether the spiders use local cues or they rely solely on global cues.
      Individually marked male spiders were captured during their excursions and
      displaced several meters inside an opaque box. Ten out of twelve displaced
      spiders returned to their burrows. This shows that the male L. arenicola are
      using local cues during their homing, as the comparatively small displacement
      distances could not be detected by means of global, e.g. celestial cues. In order
      to test whether the spiders could be using olfactory guidance, the burrows were
      displaced by 2 m while the spiders were out on their journeys. In 12 out of 15
      experiments, the spiders did not find their burrows. These results show that the
      burrows do not function as olfactory beacons for the homing spiders.

PMID- 17235607
TI  - Factors contributing to the enhancement of MDMA-induced 5-HT depletion by
      ethanol: a reply to Byron and Cassel.

PMID- 17235608
TI  - Cellular nicotinic receptor desensitization correlates with nicotine-induced
      acute behavioral tolerance in rats.
AB  - RATIONALE: Individuals vary in their susceptibility to nicotine addiction.
      However, there is little evidence that behavioral sensitivity to nicotine is
      dependent upon the functional state of nicotinic cholinergic receptors (nAChRs).
      OBJECTIVE: This study aims to determine the relationship between in vivo
      behavioral desensitization and in vitro desensitization of nAChR function.
      METHODS: Male Sprague-Dawley rats trained to discriminate nicotine were tested
      for development of acute behavioral tolerance. The rats were injected with
      nicotine (0.4 mg/kg free base, s.c.), tested for nicotine discrimination for 2
      min, then injected with the same dose of nicotine 90, 180, and 270 min after the
      first injection and tested for nicotine discrimination after each injection.
      Susceptibility of nAChRs of individual rats to desensitization was assessed by
      use of the (86)Rb(+) efflux assay using synaptosomes prepared from the
      "thalamus," which included the hypothalamus and midbrain as well as the thalamic
      nuclei. To desensitize nAChRs, synaptsosomes were superfused with low
      concentrations of nicotine (5, 10, 20, and 30 nM) before stimulation of (86)Rb(+)
      efflux with nicotine (10 muM). RESULTS: The slopes of the behavioral
      desensitization were plotted as a function of the decline of nicotine-stimulated
      (86)Rb(+) efflux after in vitro desensitization. A significant correlation was
      observed between the in vitro desensitization of thalamic (86)Rb(+) efflux and
      the extent of behavioral desensitization of individual rats. CONCLUSIONS: These
      findings are consistent with the idea that production of acute behavioral
      tolerance by nicotine is related to its ability to induce nAChR desensitization
      at the cellular level.

PMID- 17235609
TI  - The amino acid L-lysine blocks the disruptive effect of phencyclidine on prepulse
      inhibition in mice.
AB  - RATIONALE: The cognitive and attentional deficits observed in schizophrenic
      patients are now considered central to the pathophysiology of the disorder. These
      deficits include an inability to filter sensory input as measured by, e.g.,
      prepulse inhibition (PPI) reflex. Administration of phencyclidine (PCP), a drug
      that can induce a schizophrenia-like psychosis in humans, disrupts PPI in
      experimental animals. In rodents, this PCP-induced deficit can be blocked by
      pretreatment with nitric oxide (NO) synthase inhibitors. This suggests that some
      of the behavioral effects of PCP are mediated via NO. The substrate for in vivo
      NO production is L-arginine, and active transport of L-arginine via the cationic
      amino acid transporter may serve as a regulatory mechanism in NO production.
      OBJECTIVES: The aim of the present study was to study the effects of L-arginine
      transport inhibition, using acute and repeated L-lysine treatment, on PCP-induced
      disruption of PPI in mice. RESULTS: Subchronic, and to some extent acute,
      pretreatment with L-lysine blocked a PCP-induced deficit in PPI without affecting
      basal PPI. CONCLUSIONS: L-lysine has been shown to block L-arginine transport in
      vitro, most likely via a competitive blockade and down regulation of cationic
      amino acid transporters. However, the importance of L-arginine transport as a
      regulatory mechanism in NO production in vivo is still not clear. The present
      results lend further support to the notion that some of the effects of PCP in the
      central nervous system are mediated via NO and that L-arginine transport may play
      a role in the regulation of NO production in the brain.

PMID- 17235610
TI  - Higher serotonin transporter occupancy after multiple dose administration of
      escitalopram compared to citalopram: an [123I]ADAM SPECT study.
AB  - OBJECTIVES: Previous studies have investigated the occupancy of the serotonin
      reuptake transporter (SERT) after clinical doses of citalopram and other
      selective serotonin reuptake inhibitors. In the present study, the occupancies of
      SERT after multiple doses of escitalopram and citalopram were compared using the
      radioligand [(123)I]ADAM and single photon emission computed tomography (SPECT).
      METHODS: Fifteen healthy subjects received escitalopram 10 mg/day (n = 6) or
      citalopram 20 mg/day (n = 9) for a total of 10 days. SERT occupancies in midbrain
      were determined with SPECT and [(123)I]ADAM at three different time points: at
      baseline (no medication) and at 6 and 54 h after last drug intake. RESULTS: At 6
      h after the last dose, mean SERT occupancies were 81.5 +/- 5.4% (mean+/-SD) for
      escitalopram and 64.0 +/- 12.7% for citalopram (p < 0.01). At 54 h after the last
      dose, mean SERT occupancies were 63.3 +/- 12.1% for escitalopram and 49.0 +/-
      11.7% for citalopram (p < 0.05). The plasma concentrations of the S-enantiomer
      were of the same magnitude in both substances. For both drugs, the elimination
      rate of the S-enantiomer in plasma was markedly higher than the occupancy decline
      rate in the midbrain. CONCLUSION: The significantly higher occupancy of SERT
      after multiple doses of escitalopram compared to citalopram indicates an
      increased inhibition of SERT by escitalopram. The results can also be explained
      by an attenuating effect of R-citalopram on the occupancy of S-citalopram at the
      SERT.

PMID- 17235611
TI  - Euphoriant effects of nicotine in smokers: fact or artifact?
AB  - RATIONALE: The claim that nicotine in cigarettes is euphoriant to smokers is
      largely based on two studies (Pomerleau and Pomerleau, Psychopharmacology,
      108:460-465, 1992; Tobacco Control, 3:374, 1994) in which smokers were instructed
      to respond to sensations of rush, buzz, or high while smoking low-nicotine or
      regular cigarettes. However, the assumption that these sensations are pleasurable
      was not tested and may have biased the results. OBJECTIVES: The aim of this study
      was to re-examine the claim that smoked nicotine is euphoriant to smokers.
      METHODS: Study 1 surveyed the frequency and pleasantness of the smoking-related
      sensations of rush, buzz, and high in a sample of smokers. Study 2 replicated
      Pomerleau and Pomerleau (Psychopharmacology, 108:460-465, 1992) with two sets of
      instruction. One set, as in the original study, defined these sensations as
      pleasurable, whereas the other defined them as unpleasant. RESULTS: Study 1 found
      that whereas rush and high were perceived as pleasant, buzz was unpleasant to
      most smokers. Study 2 found that under both sets of instructions, smokers
      reported more sensations when smoking the regular, as compared to the low
      nicotine cigarette. Additionally, the sensations of rush, buzz, and high were
      rated as more pleasant under the pleasant instructions as compared to the
      unpleasant instructions. Finally, in the pleasant instructions condition, many
      participants reported having pressed the button to indicate a pleasurable
      sensation despite having actually experienced that sensation as unpleasant.
      CONCLUSIONS: Our results suggest that the findings of Pomerleau and Pomerleau
      (Psychopharmacology, 108:460-465, 1992; Tobacco Control, 3:374, 1994) may have
      been biased by the experimental instructions and cannot be taken as evidence that
      smoked nicotine is euphoriant to smokers.

PMID- 17235612
TI  - The atypical antipsychotic, aripiprazole, blocks phencyclidine-induced disruption
      of prepulse inhibition in mice.
AB  - RATIONALE: The psychotomimetic drug, phencyclidine, induces schizophrenia-like
      behavioural changes in both humans and animals. Phencyclidine-induced disruption
      of sensory motor gating mechanisms, as assessed by prepulse inhibition of the
      acoustic startle, is widely used in research animals as a screening model for
      antipsychotic properties in general and may predict effects on negative and
      cognitive deficits in particular. Dopamine (DA) stabilizers comprise a new
      generation of antipsychotics characterized by a partial DA receptor agonist or
      antagonist action and have been suggested to have a more favourable clinical
      profile. OBJECTIVE: The aim of the present study was to investigate the ability
      of first, second and third generation antipsychotics to interfere with the
      disruptive effect of phencyclidine on prepulse inhibition in mice. RESULTS:
      Aripiprazole blocked the phencyclidine-induced disruption of prepulse inhibition.
      The atypical antipsychotic clozapine was less effective, whereas olanzapine, and
      the typical antipsychotic haloperidol, failed to alter the effects of
      phencyclidine on prepulse inhibition. CONCLUSIONS: The somewhat superior efficacy
      of clozapine compared to haloperidol may be explained by its lower affinity and
      faster dissociation rate for DA D2 receptors possibly combined with an
      interaction with other receptor systems. Aripiprazole was found to be more
      effective than clozapine or olanzapine, which may be explained by a partial
      agonist activity of aripiprazole at DA D2 receptors. In conclusion, the present
      findings suggest that partial DA agonism leading to DA stabilizing properties may
      have favourable effects on sensorimotor gating and thus tentatively on cognitive
      dysfunctions in schizophrenia.

PMID- 17235614
TI  - [Revision of the recommendations of the Commission on Pharmacotherapy of the
      German Society for Rheumatology. Comment on the use of Orthokin].
AB  - Due to the public discussion on the drug "Orthokin", the Commission for
      Pharmacotherapy of the German Society for Rheumatology (Deutschen Gesellschaft
      fur Rheumatologie, DGRh) has summarized the relevant data. An unpublished study
      with 400 patients shows an advantage for Orthokin compared to either hyaluronic
      acid or a placebo for the treatment of osteoarthritis related chronic knee pain.
      Until these data have been published in an appropriate specialist journal, it is
      not possible for the DGRh to give a recommendation.

PMID- 17235613
TI  - [Periprosthetic fractures in patients with rheumatoid arthritis].
AB  - Postoperative periprosthetic fracture is a rare but serious complication after
      joint replacement surgery. Due to poor bone quality, multiple joint involvement
      with the replacement of different joints and considerable comorbidity, the
      presence of rheumatoid arthritis is associated with a high risk of periprosthetic
      fractures. For the same reasons, periprosthetic fractures in patients with
      rheumatoid arthritis can be very difficult to treat, and their management often
      requires an interdisciplinary approach. On the basis of the current literature,
      the present work describes different aspects of the epidemiology of
      periprosthetic fractures, principles of their classification, different treatment
      options and the results of treatment of these fractures. Special attention is
      paid to the situation of patients with rheumatoid arthritis.

PMID- 17235615
TI  - New methodology for multi-dimensional spinal joint testing with a parallel robot.
AB  - Six degree-of-freedom (6DOF) robots can be used to examine joints and their
      mechanical properties with the spatial freedom encountered physiologically.
      Parallel robots are capable of 6DOF motion under large payloads making them ideal
      for joint testing. This study developed and assessed novel methods for spinal
      joint testing with a custom-built parallel robot implementing hybrid load
      position control. We hypothesized these methods would allow multi-dimensional
      control of joint loading scenarios, resulting in physiological joint motions.
      Tests were performed in 3DOF and 6DOF. 3DOF methods controlled the forces and the
      principal moment within +/-10 N and 0.25 N m under combined bending and
      compressive loads. 6DOF tests required larger tolerances for convergence due to
      machine compliance, however expected motion patterns were still observed. The
      unique mechanism and control approaches show promise for enabling complex three
      dimensional loading patterns for in vitro joint biomechanics, and could
      facilitate research using specimens with unknown, changing, or nonlinear load
      deformation properties.

PMID- 17235616
TI  - Neurological recovery after surgical decompression in patients with cervical
      spondylotic myelopathy - a prospective study.
AB  - Cervical spondylotic myelopathy is a common clinical problem. No study has
      examined the pattern of neurological recovery after surgical decompression. We
      conducted a prospective study on the pattern of neurological recovery after
      surgical decompression in patients with cervical spondylotic myelopathy. Patients
      suffering from cervical spondylotic myelopathy and requiring surgical
      decompression from January 1995 to December 2000 were prospectively included.
      Upper limbs, lower limbs and sphincter functions were assessed using the Japanese
      Orthopaedic Association (JOA) score. Assessment was done before the operation, at
      1 week, 2 weeks, 1 month, 3 months, 6 months, 1 year and then yearly after
      surgery. Results were analysed with the t-test. Differences with P-values less
      than 0.05 were regarded as statistically significant. Fifty-five patients were
      included. The average follow-up period was 53 months. Thirty-nine patients (71%)
      had neurological improvement after the operation with a mean recovery rate of
      55%. The JOA score improved after surgery, reaching statistical significance at 3
      months and a plateau at 6 months. Thirty-six patients (65%) had improvement of
      upper limb function. Twenty-four patients (44%) had improvement of lower limb
      function. Eleven patients (20%) had improvement of sphincter function. The
      recovery rate of upper limb function was 37%, of lower limb function was 23% and
      of sphincter function was 17%. Surgical decompression worked well in patients
      with cervical spondylotic myelopathy. Seventy-one percent of patients had
      neurological improvement after the operation. The neurological recovery reached a
      plateau at 6 months after the operation. The upper limb function had the best
      recovery, followed by lower limb and sphincter functions.

PMID- 17235617
TI  - Adult tibial eminence fracture fixation: arthroscopic procedure using K-wire
      folded fixation.
AB  - The purpose of this article is to describe a new and simple technique for
      arthroscopic fixation of tibial intercondylar eminence avulsion fractures using
      folded surgical pin. This technique allows reduction and fixation of the bone
      fragment without using special equipment. After standard arthroscopic procedure
      to explore the knee and to remove fracture debris and blood clot, the bone block
      is reduced and advanced with the spike of the anterior cruciate ligament tibial
      drill guide. A 1.8-mm K-wire is drilled through the guide from the proximal tibia
      into the reduced fragment. It is bent on its end into the joint with a strong
      needle case. The K-wire is then pulled back until good fragment compression to
      the tibia appears with the wire starting unbending. Next, the other side is bent
      on the anterior tibial cortex and cut. This arthroscopic fixation allows elastic
      compression fragment stabilization that authorizes early weight bearing and
      rehabilitation programs. The material is extracted by traction after 6 months.

PMID- 17235618
TI  - Endoscopic assisted posterior tibial tendon reconstruction for stage 2 posterior
      tibial tendon insufficiency.
AB  - Posterior tibial tendon insufficiency is the commonest cause of adult onset
      flatfoot deformity. The treatment of stage 2 posterior tibial tendon
      insufficiency is still controversial. Different combination of open procedures of
      tendon transfer, calcaneal osteotomy and hindfoot arthrodesis has been described.
      We describe an endoscopic approach of posterior tibial tendon reconstruction. By
      means of anterior and posterior tibial tendon tendoscopies, the medial half of
      the anterior tibial tendon is then transferred to the posterior tibial tendon.
      The construct is then augmented by side-to-side anastomosis with flexor digitorum
      longus tendon. This is supplemented with subtalar arthroereisis with a
      bioresorbable arthroereisis implant.

PMID- 17235619
TI  - Intraosseous ganglion about to cause a fracture of the glenoid: a case report.
AB  - Intraosseous ganglia of the glenoid are rare, and their etiology is unknown. This
      report describes a case of an intraosseous ganglion about to cause fracture of
      the glenoid. The patient was a 61-year-old woman with a painful left shoulder
      with a limited range of motion. Her symptoms did not improve after non-operative
      treatment. Arthroscopic examination showed a cartilage defect and erosion in the
      posteroinferior portion of the glenoid, behind which computed tomography (CT)
      showed a cystic lesion of the glenoid. There was no communication between the
      cyst and the joint space. The patient was treated by curettage and an autogenous
      cancellous bone graft from the iliac crest. Two years after the operation, the
      patient was almost free from pain, and CT showed good integration of the bone
      graft.

PMID- 17235620
TI  - Arthroscopic evaluation of ACL grafts reconstructed with the anatomical two
      bundle technique using hamstring tendon autograft.
AB  - This article describes second-look arthroscopic evaluation of the transplanted
      grafts after anatomical two-bundle ACL reconstruction, which had been performed
      between December 2000 and March 2004. Using two double-looped semitendinosus
      tendon grafts via separate femoral and tibial tunnels in the anatomical ACL
      footprints, 65 patients (mean age of 24 years) underwent anatomical two-bundle
      ACL reconstruction. The evaluation was performed for those who had undergone the
      procedure 5-29 months (mean 16.5) previously, with emphasis on graft tension and
      the presence of graft damage by meticulous probing. None of the anteromedial (AM)
      grafts showed rupture, while 11% of the posterolateral (PL) grafts showed
      substantial damage around the femoral tunnel aperture. Both the AM and PL grafts
      were evaluated as lax without apparent graft rupture in 9% of the knees. These
      results suggest that the currently performed anatomical two-bundle ACL
      reconstruction and postoperative regimen still remain to be improved to achieve
      better postoperative graft morphology.

PMID- 17235622
TI  - The role of fabric in the quasi-static compressive mechanical properties of human
      trabecular bone from various anatomical locations.
AB  - Osteoporosis leads to an increased risk of bone fracture. While bone density and
      architecture can be assessed in vivo with increasing accuracy using CT and MRI,
      their relationship with the critical mechanical properties at various anatomical
      sites remain unclear. The objective of this study was to quantify the quasi
      static compressive mechanical properties of human trabecular bone among different
      skeletal sites and compare their relationships with bone volume fraction and a
      measure of microstructural anisotropy called fabric. Over 600 trabecular bone
      samples from six skeletal sites were assessed by microCT and tested in uniaxial
      compression. Bone volume fraction correlated positively with elastic modulus,
      yield stress, ultimate stress, and the relationships depended strongly on
      skeletal site. The account of fabric improved these correlations substantially,
      especially when the data of all sites were pooled together, but the fabric
      mechanical property relationships remained somewhat distinct among the anatomical
      sites. The study confirms that, beyond volume fraction, fabric plays an important
      role in determining the mechanical properties of trabecular bone and should be
      exploited in mechanical analysis of clinically relevant sites of the human
      skeleton.

PMID- 17235623
TI  - Gene symbol: MLH1.

PMID- 17235624
TI  - Disseminated cancer cells in the bone marrow: are they really there at all?

PMID- 17235625
TI  - Gastric cancer screening using the serum pepsinogen test method.
AB  - The current status of gastric cancer screening, worldwide, as well as in Japan,
      using the serum pepsinogen test method, was reviewed. We performed a metaanalysis
      of sensitivity and specificity results from 42 individual studies (27 population
      based screening studies: n = 296 553 and 15 selected groups: n = 4 385). Pooled
      pairs of sensitivity and false-positive rates (FPr) for pepsinogen I level < or =
      70 ng/ml; pepsinogen I/II ratio < or = 3, had a sensitivity of 77%/FPr27%. The
      positive predictive value varied between 0.77% and 1.25%, and the negative
      predictive value varied between 99.08% and 99.90%. Therefore, we concluded that
      the definition of the pepsinogen test should include the pepsinogen I/II ratio,
      as consistency was obtained for both the population-based studies and the
      selected groups for those studies that used pepsinogen I serum levels together
      with the pepsinogen I/II ratio for screening for gastric cancer in high-incidence
      regions other than Japan. Individuals testing positive for extensive atrophic
      gastritis by serum pepsinogen levels undergo endoscopic examination to test for
      the presence of gastric cancer. We should increase the efficacy and cost
      effectiveness of the gastric cancer screening system, by the identification of
      groups, at low-risk, as well as those at high-risk, of developing gastric cancer,
      using a combination of assays of serum Helicobacter pylori antibody titers and
      the concentration of pepsinogen I and II. In conclusion, the pepsinogen test
      method can be used as a screening test for high-risk subjects, rather than as a
      tool for screening for cancer itself. I hope that this pepsinogen test method
      will become a world standard for gastric cancer prevention in the near future, in
      other countries, as well as in Japan.

PMID- 17235626
TI  - Assessment and data analysis of health-related quality of life in clinical trials
      for gastric cancer treatments.
AB  - This review contains a practical guide as well as a number of design and
      analytical methods for conducting health-related quality of life assessments in
      clinical trials for gastric cancer treatment. Although we address issues specific
      to the assessment of gastric cancer, many are applicable to clinical trials for
      different cancer types.

PMID- 17235627
TI  - A multicenter retrospective study of endoscopic resection for early gastric
      cancer.
AB  - BACKGROUND: The reported outcomes of endoscopic resection (ER) for early gastric
      cancer (EGC) remain limited to several single-institution studies. METHODS: A
      multicenter retrospective study was conducted at 11 Japanese institutions
      concerning their results for ER, including conventional endoscopic mucosal
      resection (EMR) and endoscopic submucosal dissection (ESD). RESULTS: A total of
      714 EGCs (EMR, 411; ESD, 303) in 655 consecutive patients were treated from
      January to December 2001. Technically, 511 of the 714 (71.6%) lesions were
      resected in one piece. The rate of one-piece resection with ESD (92.7%; 281/303)
      was significantly higher compared with that for EMR (56.0%; 230/411).
      Histologically, curative resection was found in 474 (66.3%) lesions. The rate of
      curative resection with ESD (73.6%; 223/303) was significantly higher compared
      with that for EMR (61.1%; 251/411). Blood transfusion because of bleeding was
      required in only 1 patient (0.1%) with EMR of 714 lesions. Perforation was found
      in 16 (2.2%). The incidence of perforation with ESD (3.6%; 11/303) was
      significantly higher than that with EMR (1.2%; 5/411). All complications were
      managed endoscopically, and there was no procedure-related mortality. The median
      follow-up period was 3.2 years (range, 0.5-5.0 years). In total, the 3-year
      cumulative residual-free/recurrence-free rate and the 3-year overall survival
      rate were 94.4% and 99.2%, respectively. The 3-year cumulative residual
      free/recurrence-free rate in the ESD group (97.6%) was significantly higher than
      that in the EMR group (92.5%). CONCLUSION: ER leads to an excellent 3-year
      survival in clinical practice and could be a possible standard treatment for EGC.
      ESD has the advantage of achieving one-piece resection and reducing local
      residual or recurrent tumor.

PMID- 17235628
TI  - Detection of cancer cells and gene expression of cytokines in the peritoneal
      cavity in patients with gastric cancer.
AB  - BACKGROUND: The gene expression of the cytokines interleukin-2 (IL-2) and IL-10
      in peritoneal washings was examined in relation to the presence of cancer cells
      in the peritoneal cavity in patients with gastric cancer. METHODS: Total RNA was
      extracted from 50-ml peritoneal wash samples from 124 patients (gastric cancer, n
      = 110; controls, n = 14). Carcinoembrionic antigen (CEA) messenger RNA (mRNA) was
      used to identify the number of cancer cells in peritoneal wash samples by a real
      time reverse transcription-polymerase chain reaction (RT-PCR) method, which
      method was also used to assay the IL-2 and IL-10 gene expression levels. RESULTS:
      In the 14 control samples, CEA mRNA was not detected, while CEA mRNA was detected
      in 2 of the 51 stage I gastric cancer patients. Thus, the specificity of this
      method for the detection of cancer cells in peritoneal wash samples was 97%
      (63/65). The CEA-based real-time RT-PCR method demonstrated greater prognostic
      impact than the traditional cytological method. IL-2 gene expression in
      peritoneal wash samples that were CEA mRNA-positive was suppressed compared with
      that in peritoneal wash samples that were CEA mRNA-negative, while IL-10 gene
      expression did not differ according to the CEA mRNA findings. CONCLUSION: The
      detection of small numbers of cancer cells in peritoneal wash samples from
      patients with advanced gastric cancer is a good marker for peritoneal metastatic
      recurrence. In the peritoneal cavity, cancer cells may escape from immune
      surveillance by controlling the expression of cytokines.

PMID- 17235629
TI  - Significant association between PTPN11 polymorphism and gastric atrophy among
      Japanese Brazilians.
AB  - BACKGROUND: Helicobacter pylori, especially the cytotoxin-associated antigen A
      (cagA)-positive strains, plays a crucial role in the development of gastric
      atrophy and gastric cancer. CagA delivered into gastric epithelial cells combines
      with src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2),
      possibly leading to atrophy/cancer. Our previous study found that a single
      nucleotide polymorphism (SNP; IMS-JST057927) of the PTPN11 gene encoding SHP-2,
      was associated with gastric atrophy among H. pylori-seropositive subjects. This
      study aimed to examine the reproducibility of the association among Japanese
      residing in a different circumstance. METHODS: The subjects were 918 healthy
      adult Japanese Brazilians from four different areas in Brazil. Blood was sampled
      from March to May 2001. The target SNP in intron 3 of PTPN11 was genotyped by
      polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Gastric
      atrophy was evaluated with serum pepsinogens (PGs); PG I, less than 70 ng/dl and
      PG I/II ratio, less than 3. RESULTS: The genotype frequency of PTPN11 was in
      Hardy-Weinberg equilibrium: 65.5% for G/G, 30.4% for G/A, and 4.1% for A/A. The
      PTPN11 polymorphism had no significant association with H. pylori seropositivity.
      Among the H. pylori-seropositive subjects, the odds ratios (ORs) of gastric
      atrophy were 0.93 (95% confidence interval [CI], 0.59-1.47) for the G/A genotype
      and 0.31 (95% CI, 0.10-0.95) for the A/A genotype, compared with the G/G
      genotype. CONCLUSIONS: The present study reproduced the significant association
      between the A/A genotype and reduced risk of gastric atrophy among Japanese
      outside Japan. According to the Japan Single Nucleotide Polymorphisms (JSNP)
      database (db)SNP data, the G allele is very frequent among Japanese and rare in
      Caucasians. This fact may partly explain the distribution of gastric
      atrophy/cancer in the world.

PMID- 17235630
TI  - Interleukin-1beta gene (IL-1B) and interleukin 1 receptor antagonist gene (IL
      1RN) polymorphisms and gastric cancer risk in an Omani Arab population.
AB  - BACKGROUND: Gastric cancer (GC) is the most common malignancy in Oman.
      Interleukin-1beta gene (IL-1B) and interleukin-1 receptor antagonist gene (IL
      1RN) polymorphisms have been associated with increased GC risk. No previous
      studies have examined their role in an Arab population. We tested the
      associations between polymorphisms of IL1B at positions -31, -511, and +3954 and
      the IL-1RN polymorphism [variable number of tandem repeats (VNTR) and TC
      polymorphism at the -2018 position] and GC in Omani Arab patients. METHODS:
      Genomic DNA was extracted from peripheral blood of 245 control subjects and 118
      gastric cancer patients. The DNA samples were analyzed using the TaqMan allelic
      discrimination test for IL-1B -31, -511, and +3954 polymorphisms and IL-1RN -2018
      polymorphism. The VNTR of IL-1RN was genotyped using the polymerase chain
      reaction followed by agarose gel electrophoresis. RESULTS: There was an
      association between the presence of IL-1RN*2 allele and gastric cancer [odds
      ratio (OR) = 2.2, 95% confidence interval (CI) = 1.0-3.3, P = 0.04). The GC risk
      further increased to OR = 3.5 (95% CI = 1.0-11.9) in Helicobacter pylori-positive
      patients. No association was found between any of the other polymorphisms studied
      and GC. CONCLUSION: IL-1RN polymorphism increased the risk of GC in an Omani Arab
      population, consistent with previous reports. In contrast, the IL-1B -31
      polymorphism was not associated with an increased GC risk. These findings
      underscore the role of cytokine gene polymorphisms in the development of GC and
      further support the ethnic differences in the effect of IL-1B polymorphism on GC
      carcinogenesis.

PMID- 17235631
TI  - Evaluation of the efficacy of triple therapy regimen for Helicobacter pylori
      eradication in gastrectomized patients with gastric adenocarcinoma.
AB  - BACKGROUND: The cause of cancer in the gastric stump is multifactorial, and
      Helicobacter pylori is one of these factors. Its eradication has been
      recommended; however, there are few studies about of H. pylori eradication in
      gastrectomized patients. METHODS: Twenty gastrectomized patients with gastric
      adenocarcinoma and Roux-en-Y reconstruction (study group) infected by H. pylori
      were compared with nongastrectomized patients (control group) also infected by H.
      pylori. The presence of H. pylori was determined by the ultra-quick urease test
      and from a histological sample obtained by endoscopy. Both groups received the
      same triple therapy regimen. RESULTS: The rate of eradication of H. pylori in the
      study group was 90% and in the control group, it was 85%. Sex, age, and
      postoperative time did not influence the rate of eradication. CONCLUSION: There
      were no differences in the efficacy of H. pylori eradication between the two
      groups; therefore, the triple therapy regimen is effective for the eradication of
      H. pylori in gastrectomized patients with a Roux-en-Y reconstruction.

PMID- 17235632
TI  - Impact of immunohistochemically identified lymphatic invasion on nodal metastasis
      in early gastric cancer.
AB  - BACKGROUND: Among various clinical and pathological findings, lymphatic invasion
      (Ly) is the strongest risk factor for nodal metastasis in gastric cancer.
      However, the diagnosis of Ly is subjective and often inaccurate because of the
      difficulty of detecting lymphatic vessels with conventional hematoxylin and eosin
      (HE) staining. METHODS: The distribution of lymphatics in the normal gastric wall
      was immunohistochemically characterized using a new selective marker of lymphatic
      endothelium, D2-40, in surgical specimens resected for early gastric cancer
      (EGC). Then, Ly in the primary lesion was reevaluated, and the positive (PPV) and
      negative (NPV) predictive values for nodal metastasis were comparatively examined
      for Ly detected by HE staining (Ly-HE) and by immunohistochemical staining (Ly
      IM) in 131 cases of EGC. RESULTS: D2-40-positive lymphatic vessels were observed
      in the deep proper mucosal layer, and the lymphatic vessel density (LVD) was
      extremely high in the muscularis mucosa (MM) layer. The number of Ly-IM-positive
      cases (15/131) was higher than the Ly-HE-positive cases (10/131). In 48 cases of
      intestinal-type cancer, Ly-IM had a PPV of 33.3% (2/6) and anNPV of 100% (42/42),
      which was more accurate than the corresponding figures for Ly-HE (25% and 98%,
      respectively). In contrast, the accuracy of Ly-IM was similar to that of Ly-HE in
      83 cases of diffuse-type cancer. CONCLUSION: Lymphatic vessels are most densely
      distributed in the MM layer in the gastric wall. Immunohistochemical
      identification of lymphatics is useful to increase the accuracy of diagnosing Ly
      in resected gastric EGCs. Ly-IM is superior to Ly-HE as a predictor of nodal
      metastasis, at least for intestinal-type EGC.

PMID- 17235633
TI  - The impact of obesity on LADG for early gastric cancer.
AB  - BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) has become a viable
      alternative treatment for patients suffering with early gastric cancer. Surgeons
      have long thought that obesity might increase the rate of intraoperative or
      postoperative complications. We set out to clarify the effect that obesity has on
      performing LADG for the treatment of early gastric cancer. METHODS: We
      retrospectively reviewed 97 patients who had undergone LADG for early gastric
      cancer between May 1998 and March 2004. We measured the degree of obesity by
      using the body mass index (BMI; kg/m(2)), and we compared the surgical outcomes
      between the normal BMI group (BMI < 23 kg/m(2)) and the high BMI group (BMI > or
      = 23 kg/m(2)). We further subdivided the patients into four groups: normal BMI
      males and normal BMI females, and high BMI males and high BMI females, and we
      analyzed them in terms of operation times, numbers of retrieved lymph nodes, and
      rates of postoperative complications. RESULTS: There were no significant
      differences between the normal and high BMI groups in terms of the patients'
      characteristics, surgical outcomes, postoperative courses, postoperative
      complications, and operation times. There were no statistically significant
      differences in the number of retrieved lymph nodes or in the rate of
      postoperative complications among the four groups (P = 0.5030 and P = 0.3489,
      respectively). However, there was a statistically significant difference in
      operation times among the four groups (P = 0.004). Specifically, the males in the
      high BMI group required a longer operation time than did the females with a
      normal BMI (P = 0.006) and the females with a high BMI (P = 0.019). CONCLUSIONS:
      For LADG in patients with early gastric cancer, obesity may affect the operation
      time, and men with high BMI require a longer operation time than do women with
      normal or high BMI.

PMID- 17235634
TI  - Detection of cancer cells disseminated in bone marrow using real-time
      quantitative RT-PCR of CEA, CK19, and CK20 mRNA in patients with gastric cancer.
AB  - BACKGROUND: To determine the significance of bone marrow disseminated tumor cells
      in gastric cancer, we investigated the mRNA expression levels of carcinoembryonic
      antigen (CEA), cytokeratin 19 (CK19), and cytokeratin 20 (CK20) using the real
      time quantitative reverse-transcription polymerase chain reaction (RQ-PCR).
      METHODS: Bone marrow samples were aspirated from the sternum at the time of
      surgery in 65 patients with resectable gastric cancer. Total RNA was extracted
      from bone marrow; and the expression levels of CEA, CK19, and CK20 mRNA were
      determined by RQ-PCR using an ABI PRISM 7000 and quantified against the GAPDH
      mRNA level. RESULTS: The detection limits of these genes were determined in the
      gastric cancer cell line MKN-45 and the colon cancer cell line C-1, which had
      been serially diluted in peripheral blood mononuclear cells (PBMCs). A rate of 1
      cancer cell/million PBMCs was obtained by detecting CEA and CK19 mRNA in MKN-45
      and by detecting CK20 mRNA in C-1. In the clinical samples, only 1 of the 65
      gastric cancer patients (1.5%) who had stage IV disease was positive for CEA,
      CK19, and CK20 mRNA; none of CEA, CK19, or CK20 mRNA was positive in the
      remaining 64 patients. No significant correlation was observed between
      disseminated cancer cells in bone marrow and clinicopathological features,
      including simultaneous or metachronous hepatic metastasis and patient survival.
      CONCLUSION: The incidence of disseminated cancer cells in bone marrow in our
      study appears low, unlike that in previous reports. The significance of
      disseminated cancer cells in bone marrow may also be quite low in gastric cancer.

PMID- 17235635
TI  - Detection of early gastric cancer: misunderstanding the role of mass screening.
AB  - BACKGROUND: The proportion of early gastric cancer (EGC) increased from 15%
      during the 1960s to 50% recently, leading to a remarkable improvement of the 5
      year survival rate of gastric cancer patients from 40% to 70%. This has been
      attributed to mass screening together with extended lymphadenectomy. However,
      more and more patients with EGC are diagnosed outside of mass screening. The aim
      of this study was to determine whether patients are symptomatic at the time of
      early detection and the method of tumor detection. METHODS: From 2001 to 2003, a
      total of 1226 patients (male/female 2.2 : 1.0, age 26-95 years) with EGC were
      treated at the National Cancer Center Hospital, Tokyo. We reviewed their medical
      records. RESULTS: Of these 1226 patients, 512 (41.8%) were symptomatic, and 714
      (58.2%) reported no symptoms. Among the symptomatic patients, 468 (91.4%) were
      examined at outpatient clinics, 39 (7.6%) by private health assessment clinics,
      and 5 (1.0%) by mass screening. In total, 91.6% of the symptomatic patients
      directly underwent esophagogastro-duodenoscopy (EGD). Of the asymptomatic
      patients, 320 (44.8%) were examined at outpatient clinics, 306 (42.9%) by private
      health assessment clinics, and 88 (12.3%) by mass screening. EGD was the initial
      assessment in 67.8% and radiography in 32.2% of asymptomatic patients.
      CONCLUSION: Most patients with EGC were detected outside of mass screening. This
      suggests that the Japanese public and physicians are well aware of the risk of
      gastric cancer and the importance of early detection. The effect of mass
      screening is misunderstood.

PMID- 17235636
TI  - Early gastric cancer located just above Dieulafoy's ulcer, with massive bleeding.
AB  - In 2003, a 69-year-old man visited our emergency department because of
      hematemesis and anemia. Emergency gastroscopy revealed massive bleeding from
      Dieulafoy's ulcer in the upper body of the stomach. The arterial bleeding was
      successfully controlled by endoscopic clipping. Blood transfusion and a proton
      pump inhibitor were administered and his condition recovered smoothly. Two weeks
      after the treatment, type IIa early gastric cancer was detected at the previous
      bleeding point by follow-up endoscopy. He underwent distal gastrectomy with
      systematic lymph node dissection (D2), and he had no sign of recurrence until
      2005. Histopathological examination revealed an early gastric cancer with
      submucosal invasion located just above the Dieulafoy's disease. The
      characteristic finding of Dieulafoy's disease was an enlarged and tortuous artery
      arising from the subserosa, penetrating the muscle layer, and spreading in the
      submucosa. Abnormal Dieulafoy's artery coexisting with gastric cancer has been
      reported in only 17 cases until now. Our clinical and pathological findings led
      us to the following speculation on the pathogenesis in our patient. Repeated
      regeneration of the mucosal membrane would have been caused by circulatory
      disturbance in Dieulafoy's vessels. This regeneration and mucosal dysplasia may
      have been a factor in promoting the gastric cancer. In the previously reported
      cases of the coexistence of abnormal Dieulafoy's artery and gastric cancer, the
      initial gastroscopic examination rarely diagnosed the gastric cancer. Thus,
      follow-up gastroscopy is essential, so as not to miss such coexisting diseases.

PMID- 17235638
TI  - Current status of measles in Japan: molecular and seroepidemiological studies.
AB  - On account of the measles vaccination campaign, with vaccinations carried out on
      the first birthdays of children, the number of reported cases of measles was
      reduced to 545 in 2005, which is the lowest so far in Japan. We conducted a
      molecular epidemiological study of measles virus to determine the circulating
      measles virus genotypes in Japan since 1984. Different genotypes, C1, D3, D5, and
      H1, were the major strains isolated in outbreaks in 1984, 1987-1988, 1991-1993,
      and 2000, respectively. When measles was in the control phase, a sporadic
      outbreak was reported, but the causative virus was found to be of imported
      measles virus lineage. We also conducted a seroepidemiological study to
      investigate the persistence of vaccine-acquired immunity in Himeji City, Japan.
      Before 1990, vaccine coverage was 84.5% and it increased gradually, to 88.5% in
      1991-1995, 92.7% in 1996-2000, and 94.6% after 2000. Measles outbreaks were
      observed annually before 1978 and in 1980, 1981, 1984, 1990, and 1996; there were
      no measles cases after 1997 in Himeji City. In 1994-1998, a serological study of
      795 sera showed that measles neutralization test (NT) antibodies were
      sufficiently preserved, even 12 years after the first-dose immunization. In 1999
      2003, 26 (3.7%) of 695 sera were negative for NT. The positive rate for measles
      NT decreased to approximately 90% as the elapsed time after the first-dose
      immunization increased to 6 or 7 years. The immunity obtained after receiving
      measles vaccine decays by 6-7 years after the first dose when the measles was
      controlled. A two-dose schedule of measles vaccine was implemented in Japan in
      2006; we should continue molecular and serological surveillance.

PMID- 17235637
TI  - Suspected paclitaxel-induced pneumonitis.
AB  - We report two patients with advanced gastric cancer with suspected paclitaxel
      induced interstitial pneumonitis. Case 1, a 66-year-old man with recurrent
      gastric cancer, was treated weekly with paclitaxel. After 11 administrations of
      paclitaxel, he developed a nonproductive cough and dyspnea. Computed tomography
      (CT) scan showed extensive bilateral areas of ground-glass attenuation. He did
      not respond to corticosteroid, and died 57 days after the last paclitaxel
      administration. Case 2, a 61-year-old man with gastric cancer and liver
      metastasis, was treated with weekly paclitaxel. The liver metastasis was
      dramatically reduced in size, but he developed a nonproductive cough and dyspnea
      after 21 administrations of paclitaxel. He did not respond to high-dose
      corticosteroid, and died 50 days after the last paclitaxel administration.
      Although it is a rare complication, paclitaxel-induced interstitial pneumonitis
      needs to be considered in the differential diagnosis when patients treated with
      paclitaxel present with fever, nonproductive cough, and dyspnea.

PMID- 17235639
TI  - The vapor activity of oregano, perilla, tea tree, lavender, clove, and geranium
      oils against a Trichophyton mentagrophytes in a closed box.
AB  - The vapor activity of six essential oils against a Trichophyton mentagrophytes
      was examined using a closed box. The antifungal activity was determined from
      colony size, which was correlated with the inoculum size. As judged from the
      minimum inhibitory dose and the minimum fungicidal dose determined after vapor
      exposure for 24 h, the vapor activity of the six essential oils was ranked in the
      following order: oregano > clove, perilla > geranium, lavender, tea tree. The
      vapors of oregano, perilla, tea tree, and lavender oils killed the mycelia by
      short exposure, for 3 h, but the vapors of clove and geranium oils were only
      active after overnight exposure. The vapor of oregano and other oils induced
      lysis of the mycelia. Morphological examination by scanning electron microscope
      (SEM) revealed that the cell membrane and cell wall were damaged in a dose- and
      time-dependent manner by the action of oregano vapor, causing rupture and peeling
      of the cell wall, with small bulges coming from the cell membrane. The vapor
      activity increased after 24 h, but mycelial accumulation of the active oil
      constituents was maximized around 15 h, and then decreased in parallel with the
      decrease of vapor concentration. This suggested that the active constituent
      accumulated on the fungal cells around 15 h caused irreversible damage, which
      eventually led to cellular death.

PMID- 17235640
TI  - Efficacy of intravenous itraconazole against invasive pulmonary aspergillosis in
      neutropenic mice.
AB  - The efficacy of itraconazole (ITZ) solubilized in hydroxypropyl-beta-cyclodextrin
      (ITZ-IV) was examined in a murine model of invasive pulmonary aspergillosis
      (IPA). Immunosuppressed mice were infected by the intratracheal inoculation of
      Aspergillus fumigatus conidia (2 x 10(6) conidia/mouse). Their body weight
      rapidly decreased and they died within 6 days after infection. Intravenous
      administration of various doses of ITZ-IV was started 24 h after infection and
      was continued once a day for 4 days. ITZ-IV at daily doses of 10, 20, or 40 mg/kg
      was as effective as the intraperitoneal administration of amphotericin B (AMPH)
      at a dosage of 1 mg/kg daily in improving survival. ITZ-IV (20 mg/kg per day), as
      well as AMPH (1 mg/kg per day) significantly lowered the fungal burden in the
      pulmonary tissues. Histological improvement was seen within 2 days after the
      beginning of administration of ITZ-IV (20 mg/kg per day). In mice intravenously
      given a single dose of ITZ-IV (20 mg/kg), the blood level and pulmonary tissue
      level of ITZ plus its active metabolites, mainly hydroxyitraconazole (OH-ITZ),
      decreased gradually after the injection, but after 4 h their concentration was
      still between 1.4 microg/ml (ITZ) and 1.9 microg/ml (OH-ITZ), concentrations that
      were approximately 10 to 20 times greater than the minimum inhibitory
      concentration (MIC) of ITZ for challenging the strain of A. fumigatus (0.16
      microg/ml). These results support the clinical usefulness of ITZ-IV for the
      treatment of IPA in immunocompromised patients.

PMID- 17235641
TI  - To reduce catheter-related bloodstream infections: is the subclavian route better
      than the jugular route for central venous catheterization?
AB  - The most important targets of hospital-acquired infection control are to reduce
      the incidence of surgical-site, catheter-related, and ventilator-associated
      infections. In this report, we address previously presented infection-control
      strategies for central venous (CV) line catheterization, using a CV catheter
      related infection surveillance system. Data concerning CV catheter insertion were
      collected from all facilities in our 650-bed hospital, excluding the operating
      and hemodialysis wards. Collected data included the insertion method, purpose,
      length of catheter inserted, duration of catheterization, infection rate, and
      complication rate. Catheter-related infection was diagnosed based on
      bacteriological examinations from blood cultures. The total number of
      catheterizations was 806 a year, and average duration of catheterization was 9.8
      days. The purpose of catheterization was nutritional support in 210 cases,
      hemodialysis in 96 cases, cardiac support in 174 cases, and other treatments in
      260 cases. In 66 cases, the purpose of CV catheter was not specified. The rate of
      positive cultures was 7.1%, and complications other than infection occurred in
      0.5%. The main causative organisms were methicillin-resistant Staphylococcus
      aureus (MRSA) in 38.6%, coagulase-negative Staphylococcus epidermidis (CNS) in
      33.3%, and S. aureus in 12.3% of infections. Infection rates were 3.8 per 1000
      catheter-days in subclavian, 6.1 in jugular, and 15.7 in femoral vein
      catheterization. In high-risk departments (intensive care unit [ICU] and
      emergency departments) the infection rate was 5.4 for subclavian and 10.2 for
      jugular catheterization, whereas it was 3.6 for subclavian and 4.6 for jugular
      catheterization in noncritical-care departments. Considering complications such
      as pneumothorax, CV catheterization of the jugular vein is recommended in certain
      situations.

PMID- 17235642
TI  - Alterations of pbp1a, pbp2b, and pbp2x in Streptococcus pneumoniae isolates from
      children with otolaryngological infectious disease in the Sapporo district of
      Japan.
AB  - Evaluation of beta-lactam susceptibility and polymerase chain reaction (PCR)
      based genotyping of penicillin-binding proteins (PBP) 1A, 2B, and 2X were
      performed for Streptococcus pneumoniae isolates from children with
      otolaryngological infectious disease in the Sapporo district, Hokkaido
      Prefecture, Japan. Of 174 S. pneumoniae isolates, 14 (8%) were penicillin
      resistant S. pneumoniae (PRSP), 87 (50%) were penicillin-intermediately
      resistant, and 73 (42%) were penicillin-sensitive. Seventy-six (44%) had
      alterations in all of the three genes examined (pbp1a, pbp2b, and pbp2x), 81
      (47%) had alterations in one or two of the genes, and 17 (10%) had no
      alterations. Isolates with alterations in all three genes showed low
      susceptibility to penicillin, while, in contrast, isolates with no alteration
      showed relatively high susceptibility to penicillin. Similar relationships were
      observed for other beta-lactams. The prevalence of PRSP in our study ranged from
      5% to 12.8% (average, 8%), and there was much variation in the prevalence of PBP
      gene alterations among the cities. The results suggest that local differences in
      patterns of PBP gene alterations can be observed even at the district level. PCR
      based genotyping of PBP genes is rapid, convenient, and useful to investigate
      genetic susceptibility to beta-lactams. Further, not only nationwide or
      prefectural surveys but also local surveillance at the district level is
      important for determining antimicrobial susceptibility status in daily practice.

PMID- 17235643
TI  - Etiology and clinical study of community-acquired pneumonia in 157 hospitalized
      children.
AB  - We tried to verify whether the currently employed diagnosis and treatment of
      community-acquired pneumonia in children were appropriate. For this purpose, we
      created tentative criteria for the classification of pediatric community-acquired
      pneumonia. We classified the community-acquired pneumonia into ten categories:
      (1) bacterial, (2) concomitant viral-bacterial, (3) viral, (4) mycoplasmal, (5)
      concomitant mycoplasmal-bacterial, (6) concomitant mycoplasmal-viral, (7)
      chlamydial, (8) concomitant chlamydial-bacterial, (9) concomitant chlamydial
      viral, and (10) unknown. Children aged 1 month to 13 years with radiographic and
      clinical evidence of pneumonia were enrolled. Between October 2001 and September
      2002, we enrolled 165 patients. The etiologic agents were determined in 126 of
      the 157 (80.3%) patients who were finally diagnosed with pneumonia. Two blood
      cultures were positive for Haemophilus influenzae type b and Streptococcus
      pneumoniae. A viral infection alone was found in 28 of the 157 patients (17.8%),
      a bacterial (without mycoplasmal) alone infection in 42 (26.8%), a concomitant
      viral-bacterial infection in 28 (17.8%), and a mycoplasmal infection in 27
      (17.2%) patients. RS virus was identified in 28 patients (17.8%), influenza A in
      12 (7.6%), parainfluenza 3 in 8 (5.1%), adenovirus in 8 (5.1%), and influenza B
      and measles virus in 1 patient each. Streptococcus pneumoniae was the most common
      cause of bacterial pneumonia. We chose the initial treatment according to
      clinical and laboratory findings on admission (i.e., patients' age, clinical
      course, chest X-ray, and laboratory findings). In 68 of the 71 patients with
      bacterial (without mycoplasmal) pneumonia, an appropriate antibacterial-agent was
      prescribed. In 25 of the 27 patients with mycoplasmal pneumonia, clindamycin and
      minocycline were prescribed.

PMID- 17235644
TI  - Clinical characteristics and outcomes of bacteremia caused by Acinetobacter
      species other than A. baumannii: comparison with A. baumannii bacteremia.
AB  - Previous reports have suggested that bacteremia caused by Acinetobacter species
      other than A. baumannii is frequently associated with intravascular catheters,
      and that A. baumannii is less virulent than non-baumannii Acinetobacter. To
      validate these observations, 28 patients with bacteremia caused by Acinetobacter
      species other than A. baumannii (cases) were compared with 112 randomly selected
      patients with A. baumannii bacteremia (controls). Only 1/28 (3.6%) case episodes
      and 13/112 (11.6%) control episodes of bacteremia were definitely catheter
      related (P = 0.301). Even if probable catheter-related episodes were included,
      the frequency did not differ significantly between cases and controls (46.4% vs
      39.3%; P = 0.491). No significant differences between cases and controls were
      noted in crude mortality (17.9% vs 32.4%; P = 0.131) or bacteremia-related
      mortality (14.3% vs 12.6%; P = 0.760). In conclusion, we found that the portals
      of entry and the mortality of bacteremia associated with Acinetobacter species
      other than A. baumannii and with A. baumannii were similar.

PMID- 17235645
TI  - Neutrophil alkaline phosphatase activity in respiratory viral infection.
AB  - Neutrophil alkaline phosphatase (NAP) is used as a diagnostic marker in several
      hematological disorders. In regard to the role of NAP in infectious diseases,
      previous investigators have presented the hypothesis that NAP activity is useful
      to distinguish viral infections from bacterial infections. Because the numbers of
      patients enrolled in previous studies of viral infections were limited, we
      intended to evaluate the hypothesis by measuring NAP activity in a large number
      of pediatric patients with respiratory viral infections. A cytochemical analysis
      of NAP was performed in 160 patients with various types of respiratory
      infections. In patients with adenovirus or respiratory syncytial (RS) virus
      infection, NAP activity was significantly higher than the control value newly
      established at our department, while in patients with Epstein-Barr virus,
      measles, or influenza infection, it was comparable to the control value. On an
      individual basis, NAP scores (determined from NAP cytochemical activity) in 22 of
      26 patients (84.6%) with adenovirus infection, and 31 of 42 patients (73.8%) with
      RS virus infection were found to exceed the 95% confidence upper limit of the
      control group. In conclusion, NAP activity is quite varied among different
      respiratory viral infections. When NAP activity is high in respiratory
      infections, adenovirus or RS virus infection, as well as bacterial infections,
      should be taken into consideration.

PMID- 17235646
TI  - Quinupristin/dalfopristin and voriconazole controlled Staphylococcus epidermidis
      pneumonia and chronic necrotizing aspergillosis in a patient with severe lung
      degradation consequent to multiple treatments for Hodgkin's lymphoma.
AB  - We report here a 34-year-old woman with complicated severe opportunistic
      pulmonary infection, who was treated with the newly developed antibiotics
      quinupristin/dalfopristin (QPR/DPR) and voriconazole. She had received repeated
      chemotherapy, irradiation of the left lung, autologous and allogeneic bone marrow
      transplantation (BMT), and segmentectomy of the base of the left lung as
      treatments for Hodgkin's lymphoma. Although she had been in complete remission
      (CR), the structure of the left lung was severely degraded. Four years after
      achieving CR, she developed complicated life-threatening pulmonary infections
      with methicillin-resistant Staphylococcus epidermidis and Aspergillus niger
      during outpatient care. Chemotherapies with QPR/DPR for S. epidermidis pneumonia
      and voriconazole for chronic necrotizing pulmonary aspergillosis (CNPA) improved
      her symptoms rapidly without any major complications. QPR/DPR and voriconazole
      are considered effective for patients with life-threatening opportunistic
      pulmonary infections who have previously been treated with intensive regimens
      including radiotherapies to the lung.

PMID- 17235647
TI  - Post-dengue neuromyelitis optica: case report of a Japanese-descendent Brazilian
      child.
AB  - Monophasic neuromyelitis optica (NMO) is a rare form of post-infection acute
      disseminated encephalomyelitis (ADEM). Cases occurring after dengue virus
      infection are rare, despite the high prevalence of this disease in tropical and
      subtropical countries. We report a female patient, 11 years old, of Japanese
      ancestry and living in North Brazil, who developed NMO 1 week after having had a
      benign form of dengue fever. The disease was confirmed by the detection of dengue
      IgM antibodies in serum and cerebrospinal fluid (CSF). Restricted distribution of
      the lesions in the optic nerve and spinal cord was confirmed by ophthalmological
      evaluation and magnetic resonance imaging of the brain and spinal cord.
      Therapeutic intervention with corticotherapy resulted in benign evolution. This
      is the second report of optic spinal syndrome following dengue virus infection in
      patients of Japanese ancestry, suggesting an influence of the genetic background
      in the susceptibility to post-dengue NMO.

PMID- 17235648
TI  - A case of postmalaria neurological syndrome in Japan.
AB  - Several neurological complications are associated with severe falciparum malaria.
      Indeed, some patients experience a neurological syndrome after complete recovery
      from Plasmodium falciparum infection. Particularly, postmalaria neurological
      syndrome (PMNS) is a self-limiting post-infective encephalopathy that occurs
      within 2 months after an episode of P. falciparum infection. We describe the case
      of a 54-year-old Japanese man who was readmitted to our hospital with incoherent
      speech and markedly disturbed and uncooperative behavior after a high-grade fever
      that occurred after an earlier adequately treated severe P. falciparum infection.
      Peripheral blood smears were repeatedly negative for malaria parasites, no
      organisms were detected in the cerebrospinal fluid, and no hallmark lesions of
      acute disseminated encephalomyelitis were depicted by brain magnetic resonance
      imaging. The neuropsychiatric symptoms were thought to be due to PMNS. The
      etiology of PMNS remains unclear, but it could be mediated by an immunological
      mechanism and could possibly be caused by mefloquine treatment. PMNS must be
      considered when characteristic neurological signs and symptoms such as psychotic
      or acute confusional episodes, general convulsions, and tremor occur after
      recovery from severe P. falciparum infection treated with oral mefloquine. This
      is the first reported case of suspected PMNS in Japan.

PMID- 17235649
TI  - Ciprofloxacin therapy for typhoid fever needs reconsideration.
AB  - Outbreaks of multidrug-resistant Salmonella enterica serotype Typhi in the Indian
      subcontinent in the late 1980s resulted in the failure of conventional drugs, and
      ciprofloxacin became the firstline drug to treat enteric fever. However, reduced
      susceptibility to ciprofloxacin, reported widely since 1994, has posed a
      therapeutic difficulty. The aim of the present work was to review the situation
      of drug resistance among S. enterica serotype Typhi in central India from 1988 to
      2005. A minimum inhibitory concentration (MIC) study for ciprofloxacin was
      carried out by the agar dilution method on 314 stock cultures preserved since
      1988. The MIC for ciprofloxacin was < or = 0.125 mg/l for the 50 isolates
      isolated during 1989-1994, but during 1998-1999, 60% of the 50 isolates showed
      MIC > 0.125 mg/l, while in 2002-2003, 82.5 % of the 97 isolates had MIC > 0.125
      mg/l and 35% had MIC > 1 mg/l (high-level resistance). In 2004-2005, 88.2% of the
      77 isolates had MIC > 0.125 mg/l and 15% had MIC > 1 mg/l (high-level
      resistance). Sixty-four isolates showing MIC > 1 mg/l with the agar dilution
      method were also checked by Epsilometer test (E-test, AB Biodisk, Solna, Sweden).
      Based on the data, it is suggested to withdraw ciprofloxacin as a therapeutic
      agent for enteric fever. Fortunately, multiple drug resistance, with concurrent
      resistance to chloramphenicol, cotrimoxazole, and ampicillin, which had reached
      more than 90% in 1990-1991, started declining over the years and was as low as
      5.6% in 2004-2005. According to these observations, older drugs such as
      chloramphenicol, cotrimoxazole, and ampicillin could be recalled to treat enteric
      fever.

PMID- 17235650
TI  - Ankylosing spondylitis presenting with macrophage activation syndrome.
AB  - Macrophage activation syndrome (MAS), which can also be considered as reactive
      hemophagocytic syndrome (HPS), is a rare and potentially fatal complication of
      rheumatic diseases. We describe a 42-year-old woman in whom MAS developed as a
      complication of ankylosing spondylitis (AS). She suffered from fever and low back
      pain before admission. Laboratory findings were pancytopenia, abnormal liver
      enzymes, increased ferritin levels, and positive for B27. Hyperplasia of
      hemophagocytic macrophages was confirmed in her bone marrow. High-dose steroids
      therapy resulted in clinical and laboratory improvements. In this patient, there
      was no possible causative factor of HPS (such as viral infection, lymphoma, and
      systemic lupus erythematosus) except the presence of AS. There have been no
      previously reported cases describing the relationship between AS and HPS. This
      case indicates that attention should be given to the possibility that certain
      patients with AS-associated cytopenia may display accompanying intramedullary
      hemophagocytic phenomena.

PMID- 17235651
TI  - When to stop in the quest of formes frustes of connective tissue disease?

PMID- 17235652
TI  - Spontaneous multiple insufficiency fractures after pelvic abscess and sepsis in a
      rheumatoid arthritis patient treated with high-load corticosteroid therapy: a
      case report.
AB  - We report the unique occurrence and treatment of spontaneous multiple
      insufficiency fractures after sepsis in a patient with rheumatoid arthritis (RA).
      The patient was a 53-year-old woman with a 13-year history of RA. Her disease
      activity was not influenced by a disease-modifying antirheumatic drug (DMARD)
      regimen that included bucillamine, D-penicillamine, gold, sulfasalazine, and
      methotrexate. Due to an increased disease activity, her DMARD treatment regimen
      was changed to leflunomide. She had also undergone corticosteroid therapy with
      prednisolone ranging from 10 to 15 mg daily over the previous 8 years. She first
      presented with a wound infection at the surgical site of resection arthroplasty
      on her left foot, which had caused hematogenous dissemination that led to pelvic
      abscess and sepsis. For the next 2 years, she experienced multiple insufficiency
      fractures in parts of the ilium, sacral body, sacral ala, three thoraco-lumbar
      vertebral bodies (T12, L1, and L2), and subcapital femoral neck without low
      energy trauma. Postmenopausal osteoporosis, pelvic abscess, sepsis, decreasing
      daily activity, high RA disease activity, and high-load corticosteroid therapy
      were considered to be the causes of these fractures. Nonspecific symptoms such as
      low back pain and fever delayed diagnosis, which may have led to secondary
      fractures. Although her course after treatment was satisfactory during the study
      period, we recommend taking repetitive radiographs to detect insufficiency
      fracture for RA patients with continuing pain and reducing the corticosteroid
      dose to prevent infection and fracture.

PMID- 17235653
TI  - Decreased expressions of the TNF-alpha signaling adapters in peripheral blood
      mononuclear cells (PBMCs) are correlated with disease activity in patients with
      systemic lupus erythematosus.
AB  - Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine. Systemic lupus
      erythematosus (SLE) is an autoimmune and inflammatory disease. However, until
      now, the expression and pathophysiological role of TNF adapters in SLE have been
      poorly understood. This study aims to investigate the expression of mRNA for the
      TNF adapter proteins including TNF receptor-associated death domain (TRADD)
      protein, Fas-associated death domain (FADD) protein, receptor-interacting protein
      1 (RIP-1), and TNF receptor-associated factor-2 (TRAF-2) in peripheral blood
      mononuclear cells (PBMCs) from patients with SLE and to explore the relationship
      between the expression of these adapters and the SLE disease activity. PBMCs were
      isolated from the venous blood of 51 SLE patients and 17 healthy subjects. The
      expression of mRNA for TNF adapter molecules such as TRADD, FADD, RIP-1, and TRAF
      2 in PBMCs were analyzed by semiquantitative reverse transcription-polymerase
      chain reaction (RT-PCR) and quantitative real-time RT-PCR. There were
      constitutive expressions of mRNA for TRADD, FADD, RIP-1, and TRAF-2 in PBMCs from
      healthy subjects. The expression of mRNA for all the adapter molecules
      significantly decreased in PBMCs from patients with SLE, which were 0.38-, 0.69-,
      0.59-, and 0.55-fold, respectively, compared to those of control subjects (P <
      0.05). The expression of Caspase 3 was significantly increased in SLE patients (P
      < 0.01); however, the expression of IL-1beta was not significantly different
      between SLE and control subjects. The expression of TRADD, FADD, RIP-1, and TRAF
      2 in PBMCs from patients with SLE were negatively correlated with SLEDAI, the
      correlation coefficient of which was -0.285, -0.280, -0.307, and -0.298,
      respectively (P < 0.05). The expression of mRNA for TNF adapter molecules TRADD,
      FADD, RIP-1, and TRAF-2 decreased significantly in PBMCs from patients with SLE,
      and the expression of these adapters were negatively correlated with the SLE
      activity index. These abnormalities may be involved in the immunopathogenic
      injury mediated by the aberration TNF-alpha signaling pathway in SLE.

PMID- 17235654
TI  - Surgical outcomes and risk factors for postoperative complications in patients
      with Behcet's disease.
AB  - This study aims to investigate surgical outcomes in patients with Behcet's
      disease (BD) and to identify risk factors for the occurrence of postoperative
      complications. The medical records of 37 patients with newly diagnosed BD were
      reviewed retrospectively. All patients fulfilled the International Study Group
      criteria for diagnosis of BD and underwent surgeries after diagnosis.
      Demographic, clinical, and laboratory data at the time when surgeries were
      performed were collected and surgical modalities, postoperative complications,
      and postoperative medical treatments were evaluated. Forty-three surgeries were
      performed in 37 patients. During mean follow-up duration of 78.2 +/- 50.3 months,
      14 surgeries (32.6%) were complicated by wound dehiscence, infection, and graft
      occlusion or failure with the mean lag time of 6.0 +/- 4.6 months from surgeries.
      Cumulative incidence of postoperative complications was 7.7% at 3 months, 25.6%
      at 6 months, 33.3% at 12 months, and 35.9% at 18 months. Postoperative
      complications occurred more frequently after surgeries that were performed in
      patients with positive pathergy test (P < 0.001) and after vascular surgeries
      than after nonvascular surgeries (P < 0.05). Moreover, surgeries that were
      followed by glucocorticoids with immunosuppressive agents showed a significantly
      lower postoperative complication rate compared to those that were followed by
      glucocorticoids alone and those that were not followed by medical treatment (P <
      0.05). Multivariate analysis showed that a positive pathergic reaction (P < 0.05,
      hazard ratio = 1.91) at the time of surgery and surgeries that were not followed
      by treatment with glucocorticoids and immunosuppressive agent (P < 0.01, hazard
      ratio = 2.11) was an independent risk factor for the occurrence of postoperative
      complications. Our findings suggest that the occurrence of postoperative
      complications can be reduced when postsurgical immunosuppressive treatment was
      implemented and that the pathergy test can be used as screening methods for
      occurrence of postoperative complications in patients with BD.

PMID- 17235655
TI  - A national survey to assess investigation and management protocols followed in
      dealing with steroid-induced osteoporosis.
AB  - We assessed investigations and management protocols for patients starting long
      term steroid therapy. Rheumatology, respiratory, hematology, oncology, and
      gastroenterology consultants were asked five questions designed to assess
      investigation and management protocols followed in dealing with 50-year-old male,
      25- and 75-year-old female patients. The response rates were as follows:
      rheumatologists 11/14 (78.6%), gastroenterologists 19/31 (61.3%), respiratory
      physicians 13/26 (50%), hematologists 10/25 (40%), oncologists 6/21 (28.6%). In
      50-year-old men, calcium + vitamin D was recommended by 6/11 (54.54%)
      rheumatologists, 7/13 (53.84%) respiratory physicians, 5/10 (50%) hematologists,
      2/6 (33.33%) oncologists, and 13/19 (68.42%) gastroenterologists. Bisphosphonates
      were recommended by 3/11 (27.22%) rheumatologists, 8/13 (61.53%) respiratory
      physicians, 2/10 (20%) hematologists, and 5/19 (26.31%) gastroenterologists. Bone
      densitometry was considered by 4/11 (36.36%) rheumatologist, 3/13 (23.07%)
      respiratory physicians, 2/10 (20%) hematologists, 8/19 (42.10%)
      gastroenterologists. Calcium, phosphate, and alkaline phosphate were checked by
      3/11 (27.27%) rheumatologists, 3/13 (23.07%) respiratory physicians, 2/10 (20%)
      hematologists, 3/6 (50%) oncologists, 6/19 (31.57%) gastroenterologists. In 25
      year-old women, 4/11 (36.37%) rheumatologists, 3/13 (23.07%) respiratory
      physicians, 2/10 (20%) hematologists, 1/6 (16.66%) oncologists, and 4/19 (21.05%)
      gastroenterologists considered bone densitometry. Calcium, phosphate, and
      alkaline phosphatase were checked by 3/11 (27.27%) rheumatologists, 1/13 (07.69%)
      respiratory physicians, 3/10 (30%) hematologists, 3/6 (50%) oncologists, and 6/19
      (31.57%) gastroenterologists. Calcium + vitamin D treatment was favored by 8/11
      (72.72%) rheumatologists, 8/13 (61.51%) respiratory physicians, 5/10 (50%)
      hematologists, 2/6 (33.33%) oncologists, 14/19 (73.68%) gastroenterologists.
      Bisphosphonates were considered by 2/18 (18.18%) rheumatologists, 6/13 (46.15%)
      respiratory physicians, 1/10 (10%) hematologists, 1/6 (16.66%) oncologists, and
      3/19 (15.78%) gastroenterologists. In 70-year-old women, calcium + vitamin D was
      recommended by 8/11 (72.72%) rheumatologists, 9/13 (69.23%) respiratory
      physicians, 5/10 (50%) hematologists, 2/6 (33.33%) oncologists, and 15/19
      (78.94%) gastroenterologists. Bisphosphonates were considered by 9/11 (81.81%)
      rheumatologists, 13/13 (100%) respiratory physicians, 9/10 (90%) hematologists,
      2/6 (33.33%) oncologists, and 18/19 (94.73%) gastroenterologists. Reloxifene was
      considered by 4/11 (36.36%) rheumatologists and 2/6(33.33%) oncologists. This
      survey demonstrates the lack of consensus in investigating and treating male and
      young female patients at risk, exceptions being elderly women.

PMID- 17235656
TI  - Bilateral vocal fold immobility in a patient with overlap syndrome rheumatoid
      arthritis/systemic sclerosis.
AB  - Bilateral vocal fold immobility (BVFI) can be the result of a primary disorder or
      as an iatrogenic complication of surgery or intubation. Laryngeal involvement can
      be a rare complication of connective tissue disorders and it usually occurs in
      association with other symptoms and signs that indicate active disease. We
      present a case of BVFI in a patient with an overlap syndrome rheumatoid
      arthritis/systemic sclerosis, referred to our division because of dysphonia and
      dyspnea. The video-laryngostroboscopy showed the presence of BVFI. Physical
      examination, blood tests, lung and neck high resolution computed tomography scans
      did not demonstrate significant abnormalities. She was treated with pulses of
      intravenous methylprednisolone with slow improvement.

PMID- 17235657
TI  - Autonomic dysfunction and microvascular damage in systemic sclerosis.
AB  - Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular
      damage and interstizial fibrosis of many organs. Our interest was focused on the
      evaluation of cardiac autonomic function by measurements of heart rate
      variability (HRV) and microvascular damage detected by nailfold capillaroscopy
      (NC) in SSc patients. We examined 25 consecutive outpatients affected by systemic
      sclerosis and 25 healthy controls. Exclusion criteria were the presence of
      cardiac disease, hypertension, diabetes mellitus, or neurological diseases. All
      subjects underwent 24-h ambulatory ECG Holter recording and NC examination. Heart
      rate variability was evaluated in the time domain, using appropriate software,
      computing the time series of all normal-to-normal (NN) QRS intervals throughout
      the 24-h recording period. A semiquantitative rating scale was adopted to score
      the NC abnormalities, as well as a rating system for avascular areas and
      morphological NC patterns. In SSc patients, HRV analysis showed significantly
      lower values of SDNN (standard deviation of all NN intervals) (p=0.009), SDANN
      (standard deviation of the averages of NN intervals in all 5-min segments of the
      entire recording) (p=0.01), and pNN50 (the percentage of adjacent NN intervals
      that differed by more than 50 ms) (p=0.02), compared to the control group. These
      parameters in SSc patients significantly decreased with the worsening of
      semiquantitative capillaroscopy score. In conclusion, an abnormal autonomic
      nervous control of the heart might contribute to identify subclinical cardiac
      involvement in SSc patients. The coexistence of autonomic dysfunction with a more
      severe microvascular damage could be considered a potential prognostic tool in
      the identification of those patients particularly at risk for cardiac mortality.

PMID- 17235658
TI  - Cerebral vasculitis in a child with Henoch-Schonlein purpura and familial
      Mediterranean fever.
AB  - In this case report, a 10-year-old girl with Henoch-Schonlein purpura (HSP) with
      severe central nervous system involvement and also having familial Mediterranean
      fever (FMF) is presented.

PMID- 17235659
TI  - Posterior pelvic floor dysfunction: there is an immediate need to standardize
      terminology.

PMID- 17235660
TI  - Vaginal wind--a treatment option.

PMID- 17235661
TI  - Vaginal pressure during daily activities before and after vaginal repair.
AB  - The objective of the study was to measure vaginal pressure during various daily
      activities in patients before and after vaginal surgery for pelvic organ
      prolapse, searching data for evidence-based activity guidelines. Vaginal pressure
      (VP) was studied in 23 patients during activities such as rest, pelvic floor
      contraction (PFC), coughing, Valsalva, rising from sitting to standing and
      lifting 2 and 5 kg with four different lifting techniques. VP was measured
      before, 1-5 days and 4-6 weeks after vaginal repair. Mean VP was four to five
      times higher during coughing and Valsalva compared to PFC and lifting 2 and 5 kg.
      Lifting in the walking position created a slightly higher VP compared to other
      lifting techniques, which did not differ. The VP did not increase when lifting 5
      kg compared to 2 kg. Mean VP during coughing and Valsalva were significantly
      lower 1-5 days after the operation. VP was not related to the type of vaginal
      repair. The results imply that post-operative counselling should concentrate more
      on treating chronic cough and constipation than restrictions of moderate physical
      activities.

PMID- 17235662
TI  - Genetic markers for ancestry are correlated with body composition traits in older
      African Americans.
AB  - Individual-specific percent European ancestry was assessed in 1,277 African
      Americans. We found significant correlations between proportion of European
      ancestry and several musculoskeletal traits, indicating that admixture mapping
      may be a useful strategy for locating genes affecting these traits. INTRODUCTION:
      Genotype data for admixed populations can be used to detect chromosomal regions
      influencing disease risk if allele frequencies at disease-related loci differ
      between parental populations. We assessed evidence for differentially distributed
      alleles affecting bone and body composition traits in African Americans. METHODS:
      Bone mineral density (BMD) and body composition data were collected for 1,277
      African and 1,790 European Americans (aged 70-79). Maximum likelihood methods
      were used to estimate individual-specific percent European ancestry for African
      Americans genotyped at 37 ancestry-informative genetic markers. Partial
      correlations between body composition traits and percent European ancestry were
      calculated while simultaneously adjusting for the effects of covariates. RESULTS:
      Percent European ancestry (median = 18.7%) in African Americans was correlated
      with femoral neck BMD in women (r = -0.18, p < 10(-5)) and trabecular spine BMD
      in both sexes (r = -0.18, p < 10(-5)) independently of body size, fat, lean mass,
      and other covariates. Significant associations of European ancestry with
      appendicular lean mass (r = -0.19, p < 10(-10)), total lean mass (r = -0.12, p <
      10(-4)), and total body fat (r = 0.09, p < 0.002) were also observed for both
      sexes. CONCLUSIONS: These results indicate that some population differences in
      body composition may be due to population-specific allele frequencies, suggesting
      the utility of admixture mapping for identifying susceptibility genes for
      osteoporosis, sarcopenia, and obesity.

PMID- 17235663
TI  - Differentiation between post-menopausal women with and without hip fractures:
      enhanced evaluation of clinical DXA by topological analysis of the mineral
      distribution in the scan images.
AB  - We introduce an algorithm to evaluate hip DXA scans using quantitative image
      analysis procedures based on the Minkowski functionals (MF) for differentiation
      between post-menopausal women with and without hip fracture. In a population of
      30 post-menopausal women, the new parameter has a highly discriminative potential
      with a performance superior to standard densitometry providing complementary
      information compared to BMD. INTRODUCTION: We introduce a novel algorithm to
      evaluate DXA scans of the hip using quantitative image analysis based on the
      Minkowski functionals (MF) to identify post-menopausal women with hip-fracture
      and to compare the results with densitometry. METHODS: BMD of 30 women (73.9 +/-
      10.3 years), 15 of whom had a recent hip fracture, is obtained by DXA using the
      "total hip" ROI. The topology of mineral distribution in the scan images is
      evaluated using the MF-based parameter MF2D. ROC analysis is employed to assess
      the discriminative potential (fracture/non-fracture). RESULTS: The area-under-the
      curve (AUC) for identification of patients with/without fractures by BMD is .72(p
      = 0.04), AUC for MF2D is .85(p = 0.001). No statistically significant correlation
      exists between MF2D and BMD. By discriminant analysis we can show that by
      combination of MF2D and BMD the outcome increases significantly: using BMD or
      MF2D alone, 63% and 70% of cases are classified correctly versus 77% of cases in
      the multivariate model. CONCLUSION: The topology-based parameter has a high
      predictive potential with respect to identification of patients with high risk of
      hip fracture, performance is superior to densitometry. The new method provides
      information complementary to BMD. Best classification results are obtained when
      BMD and MF2D are combined in a multivariate model.

PMID- 17235665
TI  - Ecology of siderophores with special reference to the fungi.
AB  - Ecology of siderophores, as described in the present review, analyzes the factors
      that allow the production and function of siderophores under various
      environmental conditions. Microorganisms that excrete siderophores are able to
      grow in natural low-iron environments by extracting residual iron from insoluble
      iron hydroxides, protein-bound iron or from other iron chelates. Compared to the
      predominantly mobile bacteria, the fungi represent mostly immobile microorganisms
      that rely on local nutrient concentrations. Feeding the immobile is a general
      strategy of fungi and plants, which depend on the local nutrient resources. This
      also applies to iron nutrition, which can be improved by excretion of
      siderophores. Most fungi produce a variety of different siderophores, which cover
      a wide range of physico-chemical properties in order to overcome adverse local
      conditions of iron solubility. Resource zones will be temporally and spatially
      dynamic which eventually results in conidiospore production, transport to new
      places and outgrow of mycelia from conidiospores. Typically, extracellular and
      intracellular siderophores exist in fungi which function either in transport or
      storage of ferric iron. Consequently, extracellular and intracellular reduction
      of siderophores may occur depending on the fungal strain, although in most fungi
      transport of the intact siderophore iron complex has been observed. Regulation of
      siderophore biosynthesis is essential in fungi and allows an economic use of
      siderophores and metabolic resources. Finally, the chemical stability of fungal
      siderophores is an important aspect of microbial life in soil and in the
      rhizosphere. Thus, insolubility of iron in the environment is counteracted by
      dissolution and chelation through organic acids and siderophores by various
      fungi.

PMID- 17235664
TI  - Prediction of absolute risk of non-spinal fractures using clinical risk factors
      and heel quantitative ultrasound.
AB  - The relationship between osteoporosis risk factors, bone quantitative ultrasound
      (QUS) and non-spinal fracture risk was estimated in a cohort of 5,201
      postmenopausal women from Spain who were prospectively evaluated during three
      years. Several clinical risk factors and low heel QUS values were independently
      associated with non-spinal fracture risk. INTRODUCTION: Low-trauma, non-spinal
      fractures are a growing source of morbidity and mortality in the elderly. The aim
      of the present study was to examine the association of heel quantitative
      ultrasound (QUS) and a series of osteoporosis and fracture risk factors, with
      incident low energy non-spinal fractures in a population of elderly women, and to
      incorporate them into fracture prediction models. METHODS: 5,201 women aged 65 or
      older were enrolled in a three-year cohort study. Participants completed an
      osteoporosis and fracture risk factors questionnaire. QUS was measured at the
      heel with a gel-coupled device. Cox-proportional hazard analyses were performed
      to evaluate the association with the first incident low-trauma non-spinal
      fracture. RESULTS: Three hundred and eleven women (6.0%) sustained a total of 363
      low-trauma fractures, including 133 forearm/wrist, 54 hip, 50 humerus, 37 leg and
      17 pelvic fractures. For every standard deviation decrease in the quantitative
      ultrasound index, the adjusted hazard ratios (95% CI) for any non-vertebral, hip,
      forearm/wrist, and humerus fractures were 1.31 (1.15-1.49), 1.40 (1.01-1.95),
      1.50 (1.19-1.89) and 1.35 (0.97-1.87), respectively. Similar results were
      observed with other QUS variables. The best predictive models indicated that age,
      a history of falls, a previous low-trauma fracture, a family history of fracture,
      a calcium intake from dairy products of less than 250 mg/day, and lower values of
      QUS parameters were independently associated with the risk of non-spinal
      fractures. CONCLUSIONS: Both clinical risk factors and QUS are independent
      predictors of risk of fragility non-spinal fractures. A prediction algorithm
      using these variables was developed to estimate the absolute risk of non-spinal
      fractures in elderly women in Spain.

PMID- 17235666
TI  - The effect of copper deficiency on the formation of hemosiderin in sprague-dawley
      rats.
AB  - We demonstrated previously that loading iron into ferritin via its own
      ferroxidase activity resulted in damage to the ferritin while ferritin loaded by
      ceruloplasmin, a copper-containing ferroxidase, was not damaged and had similar
      characteristics to native ferritin (Welch et al. (2001) Free Radic Biol Med
      31:999-1006). Interestingly, it has been suggested that the formation of
      hemosiderin, a proposed degradation product of ferritin, is increased in animals
      deficient in copper. In this study, groups of rats were fed normal diets, copper
      deficient diets, iron supplemented diets, or copper deficient-iron supplemented
      diets for 60 days. Rats fed copper-deficient diets had no detectable active serum
      ceruloplasmin, which indicates that they were functionally copper deficient.
      There was a significant increase in the amount of iron in isolated hemosiderin
      fractions from the livers of copper-deficient rats, even more than that found in
      rats fed only an iron-supplemented diet. Histological analysis showed that copper
      deficient rats had iron deposits (which are indicative of hemosiderin) in their
      hepatocytes and Kupffer cells, whereas rats fed diets sufficient in copper only
      had iron deposits in their Kupffer cells. Histologic evidence of iron deposition
      was more pronounced in rats fed diets that were deficient in copper.
      Additionally, sucrose density-gradient sedimentation profiles of ferritin loaded
      with iron in vitro via its own ferroxidase activity was found to have
      similarities to that of the sedimentation profile of the hemosiderin fraction
      from rat livers. The implications of these data for the possible mechanism of
      hemosiderin formation are discussed.

PMID- 17235667
TI  - Mysid crustaceans as standard models for the screening and testing of endocrine
      disrupting chemicals.
AB  - Investigative efforts into the potential endocrine-disrupting effects of
      chemicals have mainly concentrated on vertebrates, with significantly less
      attention paid to understanding potential endocrine disruption in the
      invertebrates. Given that invertebrates account for at least 95% of all known
      animal species and are critical to ecosystem structure and function, it remains
      essential to close this gap in knowledge and research. The lack of progress
      regarding endocrine disruption in invertebrates is largely due to: (1) our
      ignorance of mode-of-action, physiological control, and hormone structure and
      function in invertebrates; (2) lack of a standardized invertebrate assay; (3) the
      irrelevance to most invertebrates of the proposed activity-based biological
      indicators for endocrine disruptor (ED) exposure (androgen, estrogen, and
      thyroid); (4) limited field studies. Past and ongoing research efforts using the
      standard invertebrate toxicity test model, the mysid shrimp, have aimed at
      addressing some of these issues. The present review serves as an update to a
      previous publication on the use of mysids for the evaluation of EDs (Verslycke et
      al. 2004a). It summarizes recent investigative efforts that have significantly
      advanced our understanding of invertebrate-specific endocrine toxicity,
      population modeling, field studies, and transgeneration standard test development
      using the mysid model.

PMID- 17235668
TI  - Hormonal signaling in cnidarians: do we understand the pathways well enough to
      know whether they are being disrupted?
AB  - Cnidarians occupy a key evolutionary position as basal metazoans and are
      ecologically important as predators, prey and structure-builders. Bioregulatory
      molecules (e.g., amines, peptides and steroids) have been identified in
      cnidarians, but cnidarian signaling pathways remain poorly characterized.
      Cnidarians, especially hydras, are regularly used in toxicity testing, but few
      studies have used cnidarians in explicit testing for signal disruption. Sublethal
      endpoints developed in cnidarians include budding, regeneration, gametogenesis,
      mucus production and larval metamorphosis. Cnidarian genomic databases,
      microarrays and other molecular tools are increasingly facilitating mechanistic
      investigation of signaling pathways and signal disruption. Elucidation of
      cnidarian signaling processes in a comparative context can provide insight into
      the evolution and diversification of metazoan bioregulation. Characterizing
      signaling and signal disruption in cnidarians may also provide unique
      opportunities for evaluating risk to valuable marine resources, such as coral
      reefs.

PMID- 17235669
TI  - The water flea Daphnia magna (Crustacea, Cladocera) as a test species for
      screening and evaluation of chemicals with endocrine disrupting effects on
      crustaceans.
AB  - The water flea Daphnia magna (Crustacea, Cladocera) is a cyclical parthenogen,
      which can reproduce both by parthenogenesis and by sexual reproduction. With its
      ease of handling in the laboratory, several testing methods using D. magna exist
      for regulatory toxicity testing. Recently, several studies revealed that one of
      the major hormone groups in insects and crustaceans, juvenile hormones, are
      involved in the shift of reproductive mode from parthenogenesis to sexual
      reproduction (production of male neonates). Using offspring sex ratio as a new
      endpoint has made it possible to identify chemicals with juvenile hormone-like
      effects on crustaceans. The testing method using D. magna, in which offspring sex
      ratio is incorporated as a new endpoint, is now being proposed to the OECD as an
      enhanced version of the existing OECD Test Guideline 211: Daphnia magna
      reproduction test. No other clear-cut endpoint for identifying juvenile-hormone
      disrupting effects has ever been found in crustaceans than the induction of male
      neonates production in cladocerans. In this regard, it is expected that testing
      methods using D. magna are suitable for screening and risk assessment of
      chemicals with juvenile-hormone disrupting effects.

PMID- 17235670
TI  - Endocrine disruption in aquatic insects: a review.
AB  - There is mounting evidence that a wide variety of compounds can have endocrine
      disrupting effects on humans and wildlife. However, investigations so far have
      focused primarily on exposure to human and other vertebrates, with invertebrate
      findings largely restricted to marine mollusks or to the ecdysteroid and juvenile
      hormone agonists as purposely synthesized endocrine disrupters for the pest
      management of insects. This article provides a brief description of the insect
      hormone system, a short sum-up of the relevant insect groups with aquatic life
      stages, and an overview of the additional evidence for endocrine disruption in
      aquatic insects from laboratory and field studies since 1999. In addition, the
      suitability of insects as sentinels for endocrine disrupting chemicals in aquatic
      ecosystems is discussed. Conclusions are drawn and research needs are defined.

PMID- 17235672
TI  - Crustacean endocrine toxicology: a review.
AB  - Crustaceans are major constituents to aquatic ecosystems that provide a variety
      of ecological and economic services. Individual crustacean species are adept at
      occupying diverse niches and their success, in part, stems from neuro-endocrine
      signaling cascades that regulate physiology in response to environmental and
      internal cues. Peptide hormones are major signal transducers in crustaceans. The
      crustacean hyperglycemic hormone family of peptides regulates various aspects of
      growth, reproduction, and metabolism. These peptides may function as the terminal
      hormone to regulate some physiological activities or may function as
      intermediates in a signaling cascade. Ecdysteroids and terpenoids are two major
      classes of terminal signaling molecules in these cascades. Hormones from these
      two classes function independently or in concert to regulate various processes.
      Ecdysteroid signaling is subject to toxicological disruption through disturbances
      in ecdysteroid synthesis or binding of toxicants to the ecdysteroid receptor.
      Methyl farnesoate is the major terpenoid hormone of crustaceans and also is
      susceptible to disruption by environmental chemicals. However, the methyl
      farnesoate signaling pathway is poorly understood and only limited mechanistic
      confirmation for disruption of this endocrine signaling pathway exists.
      Disruption of the ecdysteroid/terpenoid signaling pathways in crustaceans has
      been associated with aberrations in growth, metamorphosis, reproductive
      maturation, sex determination, and sex differentiation. Population studies have
      revealed disruptions in crustacean growth, molting, sexual development, and
      recruitment that are indicative of environmental endocrine disruption. However,
      environmental factors other that pollution (i.e., temperature, parasitism) also
      can elicit these effects and definitive causal relationships between endocrine
      disruption in field populations of crustaceans and chemical pollution is
      generally lacking.

PMID- 17235674
TI  - Synthesis and fluorescence studies of some new fluorophores and their effect on
      hybridization of oligodeoxyribonucleotides.
AB  - Some novel fluorophores, viz. 6-(6-isobutyrylamino-1,3-dioxo-1H,3H
      benzo[de]isoquinolin-2-yl)-hexanoic acid (1), 6-(6-dimethylamino-1,3-dioxo-1H, 3H
      benzo[de]isoquinolin-2-yl)-hexanoic acid (2), 6-(6-benzoylamino-1, 3-dioxo-1H, 3H
      benzo[de]isoquinolin-2-yl)-hexanoic acid (3), 6-(6-amino-1-oxo-1H, 3H
      benzo[de]isoquinolin-2-yl)-hexanoic acid (4) and 6-(6-amino-1H,3H-benzo[de]
      isoquinolin-2-yl)-hexanoic acid (5) have been designed, synthesized and
      characterized. Their comparative fluorescence has been studied in different
      organic solvents and aqueous solutions containing inorganic ions. Out of these,
      two fluorophores, 1 and 2 have been used for labelling of nucleosides which were
      finally converted into their phosphoramidites, and used for labelling of
      oligodeoxyribonucleotides through covalent attachment. These fluorophores after
      attachment on oligodeoxyribonucleotides showed good fluorescence signals and
      higher hybridisation affinity than unlabelled oligodeoxyribonucleotides.

PMID- 17235675
TI  - Monozygotic twins concordant for female-to-male transsexualism: a case report.

PMID- 17235673
TI  - Endocrine disruption in aquatic pulmonate molluscs: few evidences, many
      challenges.
AB  - As compared to other groups of aquatic gastropods, documented examples of
      endocrine disruption in pulmonates are rather limited. This is quite surprising
      because the endocrine control of physiological functions has been extensively
      studied in these animals. In the model-species Lymnaea stagnalis, the
      neurohormonal regulation of reproduction has been thoroughly investigated, and
      the primary structure of several peptides and receptors involved in endocrine
      processes has been established. However, the use of this knowledge has been
      fairly limited in the context of ecotoxicology, to investigate the effects of
      endocrine-disrupting chemicals. The present review summarizes the main and more
      recent findings on the neuroendocrine control of reproduction in aquatic
      pulmonate snails (Basommatophora). It then comprehensively describes selected in
      vivo laboratory and semi-field studies which provide evidence for possible
      endocrine disrupting effects of estrogenic and androgenic test compounds [e.g.,
      ethynylestradiol, methyltestosterone (MT)], and of environmental contaminants
      [e.g., cadmium (Cd), tributyltin (TBT), and nonylphenol (NP), pesticides].
      Finally, challenging perspectives for future research are discussed.

PMID- 17235677
TI  - Functional self-efficacy beliefs influence functional capacity evaluation.
AB  - OBJECTIVES: The relationship between functional self-efficacy and Functional
      Capacity Evaluation (FCE) lift performance was examined in workers' compensation
      claimants' with low back pain. METHODS: A cross-sectional design was used. Forty
      two claimants with back pain and 38 subjects without back pain were enrolled.
      Subjects completed a measure of functional self-efficacy related specifically to
      lifting. Subjects also underwent FCE floor-to-waist, waist-to-overhead and
      horizontal lift testing. Potential confounders were also assessed including
      perceived disability, pain intensity, and self-rated health. Analysis included
      Pearson correlation and multivariable linear regression. RESULTS: Higher
      functional self-efficacy beliefs were highly associated with better FCE
      performance on each of the lift items tested (r = 0.50-0.73). In multivariable
      analysis, the measure of functional self-efficacy remained independently
      associated with lift performance after controlling for potential confounders.
      CONCLUSION: Functional self-efficacy beliefs appear to influence FCE lift
      performance. Strategies for altering functional self-efficacy beliefs and their
      resulting impact on patient functional performance and outcomes should be
      examined.

PMID- 17235678
TI  - Life satisfaction of workers with work-related musculoskeletal disorders in
      Brazil: associations with symptoms, functional limitation and coping.
AB  - INTRODUCTION: This study aimed at analyzing the contribution of socio
      demographic, clinical, functional and psychosocial variables toward life
      satisfaction among workers with Work-Related Musculoskeletal Disorders (WMSD).
      METHODS: A cross-sectional study was carried out with 155 workers suffering from
      WMSD in one or both upper extremities, with time since the onset of the health
      condition longer than six months. Most of the workers were women (85%) between 30
      and 49 years of age (77%) and predominantly manual laborers with elementary
      education level. MAIN OUTCOME MEASURES: Structured form for socio-demographic and
      clinical identification of the participants, the Disability of the Arm, Shoulder
      and Hand Questionnaire, the Ways of Coping Scale and the Satisfaction With Life
      Scale. RESULTS: Hierarchical multiple regression analysis was employed and the
      final model explained 23% of the variance regarding life satisfaction (adjusted
      R2 = 0.21; p = 0.0001). Single workers and those reporting higher levels of
      emotion-focused and lower levels of problem-focused coping reported lower life
      satisfaction. The strategies with which an individual copes with the disease had
      an influence on the level of life satisfaction regardless of the functional
      condition. CONCLUSIONS: In the sample studied, the strongest predictors of life
      satisfaction were the psychosocial variables, represented by coping strategies
      regarding the disease. Interventions directed at workers with WMSD that seek to
      promote well-being should favor coping in the most adaptive manner, going beyond
      the clinical realm of the disease.

PMID- 17235679
TI  - Right atrial angiography facilitates transseptal puncture for complex ablation in
      patients with unusual anatomy.
AB  - OBJECTIVE: The number of transseptal punctures performed worldwide has increased
      exponentially with the development of ablation therapies for atrial arrhythmias.
      Safe access into the left atrium in these procedures is often complicated by
      abnormal anatomy. We assessed the potential of right atrial angiography to
      facilitate transseptal puncture for atrial ablation. METHODS AND RESULTS: We
      examined all transseptal punctures performed for complex left atrial ablation in
      our centre over a 29-month period. In cases where conventional transseptal
      techniques failed, we performed orthogonal right atrial angiography to define
      cardiac anatomy and orientation. During the study period, 255 transseptal
      procedures were performed. Of these, 16 cases were complicated by distorted
      atrial anatomy, extreme cardiac rotation or unexpected location of the atria in
      relation to the diaphragm, preventing left atrial access using conventional
      fluoroscopy. The application of right atrial angiography facilitated successful
      transseptal puncture in all patients when use of conventional mapping catheters
      and fluoroscopy proved unhelpful. There were no complications relating to right
      atrial angiography. CONCLUSION: These cases highlight a number of difficulties
      encountered when performing transseptal punctures. Previously reported adjunctive
      techniques require specialised equipment, general anaesthesia or multiple
      catheters that may be unavailable or impede the procedure. Right atrial
      angiography is a simple and safe adjunct to conventional techniques to facilitate
      complex transseptal procedures.

PMID- 17235680
TI  - Bi-directional electrical pulmonary vein isolation as an endpoint for ablation of
      paroxysmal atrial fibrillation.
AB  - OBJECTIVE: Various approaches to pulmonary vein (PV) isolation have shown
      variable efficacy in patients with paroxysmal atrial fibrillation (AF). The
      purpose of this study is to report the efficacy and safety of routine isolation
      of all PVs using an endpoint of bi-directional electrical block. MATERIALS AND
      METHODS: This study included 85 consecutive patients who underwent PV isolation
      for symptomatic paroxysmal AF. Complete isolation of all PVs was confirmed by
      demonstration of bi-directional block: (a) loss of all PV potentials, and (b)
      failure to capture the left atrium by pacing 10-14 bipolar pairs of electrodes on
      a circumferential catheter placed at the entrance of the PV at 10 mA with 2 ms
      pulse width. Induction of AF by burst pacing was attempted after PV isolation.
      RESULTS: Freedom from symptomatic or asymptomatic AF (detected by event recorder
      or Holter monitor) was present in 85% and 76% of patients at 6 and 12 months.
      Additional mitral isthmus or posterior left atrial lines were performed in seven
      patients with inducible atrial arrhythmias after PV isolation. Atrial tachycardia
      occurred in three of these patients during long-term follow-up and in two of the
      78 patients without additional ablation. CONCLUSION: The use of bi-directional
      block circumferentially across all PV ostia as an electrophysiological endpoint
      may improve results of PV isolation for paroxysmal AF. Avoidance of routine
      additional left atrial ablation lines may decrease the risk of atrial tachycardia
      and esophageal fistula.

PMID- 17235681
TI  - Quality of life and psychological status of patients with implantable
      cardioverter defibrillators.
AB  - INTRODUCTION: Implantable cardioverter defibrillators (ICDs) are effective at
      reducing mortality in patients at high risk for sudden cardiac death (SCD) but
      can cause psychological distress and reduce quality of life (QOL). The full
      benefits of ICDs can only be achieved when the patient's QOL and psychological
      status are maintained. We examined psychological status and QOL post ICD
      implantation; the relationship of psychological status to QOL; the relationship
      of time since implantation to psychological status and QOL; and the relationship
      of time since ICD implantation and age of patient to these variables. METHODS AND
      RESULTS: A cross-sectional self-administered assessment of QOL, depression,
      anxiety, demographic characteristics and cardiovascular health history of
      patients (n = 48) who had received ICDs within the past 10 years at an urban
      hospital. Patients who had ICDs for longer experienced worse depression and QOL.
      Patients who were younger had worse depression, anxiety, and QOL. The combination
      of anxiety, depression, age, and time since ICD implant significantly predicted
      overall QOL and the psychosocial and physical dimensions of QOL explaining 55.5,
      54, and 34.9% of the variance, respectively. CONCLUSION: Younger ICD patients are
      at highest risk for psychological distress and poor QOL. Longitudinal research
      would facilitate determination of the trajectory of changes in psychological
      status and QOL over the duration of the ICD experience.

PMID- 17235683
TI  - Design criteria of neuron/electrode interface. The focused ion beam technology as
      an analytical method to investigate the effect of electrode surface morphology on
      neurocompatibility.
AB  - "Neurocompatibility" is a broad definition which comprises aspects of
      biocompatibility, chemical and physical surface properties, and biostability of
      an artificial substrate interfaced with a neural tissue. The main issue coming
      from the analysis of the state of art of neuroprosthesis and neuron/electrode
      interfaces is the strong influence of electrode surface morphology on
      neurocompatibility. Enhanced functions of neurons have been observed on nano
      structured materials. This paper proposes the use of focused ion beam (FIB)
      technology as high precision machining technique to modify the surface morphology
      of an interface material. By controlling the ion milling in three dimensions, the
      fabrication of a surface with any predefined morphology becomes possible with
      nanometric precision. In vitro tests on PC12 cells cultured on surfaces with
      different morphologies show that the surface morphology influences the cell
      adhesion. Experimental results suggest an enhancement of the interaction between
      cells and artificial surfaces at a specific scale (tens of nanometres) which is
      the typical scale of cellular interaction in the extra-cellular matrix (ECM) of
      living organisms.

PMID- 17235682
TI  - Safety and efficacy of catheter ablation of atrial fibrillation in patients with
      diabetes mellitus--single center experience.
AB  - BACKGROUND AND OBJECTIVE: Little is known about the outcome of catheter ablation
      of atrial fibrillation (AF) in patients with diabetes mellitus (DM). We
      investigated the safety and efficacy of catheter ablation of AF in patients with
      DM. MATERIALS AND METHODS: Thirty one patients with DM from a group of 263
      consecutive patients undergoing a first-time catheter ablation of AF procedure
      were enrolled in a prospective study. The ablation protocol (guided by CARTO
      system) consisted in two continuous circular lesions around ipsilateral pulmonary
      veins. RESULTS: The following clinical characteristics differed between DM and no
      DM patients: age (62.0 +/- 10.8 vs. 56.1 +/- 10.6 years, P = 0.004), longer AF
      history (9.6 +/- 9.3 vs. 6.7 +/- 6.3 years, P = 0.024), significantly larger left
      atrium size (41.1 +/- 7.8 vs. 38.3 +/- 5.8 mm, P = 0.021), hypertension (58.1 vs.
      35.8%, P = 0.018) and structural heart disease (67.7 vs. 43.5%, P = 0.011).
      Despite a similar AF recurrence rate in DM and no-DM patients (32.3 vs. 22.4%, P
      = 0.240), the ablation procedure was complicated in 28 patients (11 hematomas,
      three cardiac tamponades and three strokes) and the incidence of complications
      was significantly higher in DM than in no-DM patients (29.0 vs. 8.2%,
      respectively, P = 0.002). Multivariate analysis showed that DM was an independent
      risk factor for complications occurrence (odd ratio 5.936, 95% confidence
      interval 2.059 to 17.112, P = 0.001). CONCLUSIONS: First catheter ablation of AF
      procedure in DM patients was equally efficacious than in no-DM patients. However,
      DM patients had a higher incidence of complications, mostly thrombotic or
      hemorrhagic.

PMID- 17235684
TI  - Arginine administration reduces creatine kinase activity in rat cerebellum.
AB  - In the present study were evaluated the in vivo effects of arginine
      administration on creatine kinase (CK) activity in cerebellum of rats. We also
      tested the influence of antioxidants, namely alpha-tocopherol and ascorbic acid
      and the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester
      (L-NAME), on the effects elicited by Arg in order to investigate the possible
      participation of nitric oxide (NO) and/or its derivatives peroxynitrite (ONOO(-))
      and other/or free radicals on the effects of arginine on CK activity. Sixty-day
      old rats were treated with a single i.p. injection of saline (control, group I),
      arginine (0.8 g/kg) (group II), L-NAME (2.0 mg/kg or 20.0 mg/kg) (group III) or
      Arg (0.8 g/kg) plus L-NAME (2.0 mg/kg or 20.0 mg/kg) (group IV) and were killed 1
      h later. In another set of experiments, the animals were pretreated for 1 week
      with daily i.p. administration of saline (control) or alpha-tocopherol (40 mg/kg)
      and ascorbic acid (100 mg/kg). Twelve hours after the last injection of the
      antioxidants, the rats received one i.p. injection of arginine (0.8 g/kg) or
      saline and were killed 1 h later. Results showed that total and cytosolic CK
      activities were significantly inhibited by arginine administration in cerebellum
      of rats, in contrast to mitochondrial CK activity which was not affected by this
      amino acid. Furthermore, simultaneous injection of L-NAME (20.0 mg/kg) and
      treatment with alpha-tocopherol and ascorbic acid prevented these effects. The
      data indicate that the reduction of CK activity in cerebellum of rats caused by
      arginine was probably mediated by NO and/or its derivatives ONOO(-)and other free
      radicals. Considering the importance of CK for the maintenance of energy
      homeostasis in the brain, if this enzyme inhibition also occurs in
      hyperargininemic patients, it is possible that CK inhibition may be one of the
      mechanisms by which arginine is neurotoxic in hyperargininemia.

PMID- 17235685
TI  - Reduced sialylation status in UDP-N-acetylglucosamine-2-epimerase/N
      acetylmannosamine kinase (GNE)-deficient mice.
AB  - Sialic acids are widely expressed as terminal carbohydrates on glycoconjugates of
      eukaryotic cells. They are involved in a variety of cellular functions, such as
      cell adhesion or signal recognition. The key enzyme of sialic acid biosynthesis
      is the bifunctional UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine
      kinase (GNE), which catalyzes the first two steps of sialic acid biosynthesis in
      the cytosol. Previously, we have shown that inactivation of the GNE by gene
      targeting causes early embryonic lethality in mice, whereas heterozygous GNE
      deficient mice are vital. In this study we compared the amount of membrane-bound
      sialic acids of wildtype mice with those of heterozygous GNE-deficient mice. For
      that we quantified membrane-bound sialic acid concentration in various organs of
      wildtype- and heterozygous GNE-deficient mice. We found an organ-specific
      reduction of membrane-bound sialic acids in heterozygous GNE-deficient mice. The
      overall reduction was 25%. Additionally, we analyzed transferrin and
      polysialylated neural cell adhesion molecule (NCAM) by one- or two-dimensional
      gel electrophoresis. Transferrin-expression was unchanged in heterozygous GNE
      deficient mice; however the isoelectric point of transferrin was shifted towards
      basic pH, indicating a reduced sialylation. Furthermore, the expression of
      polysialic acids on NCAM was reduced in GNE-deficient mice.

PMID- 17235686
TI  - p38 MAP kinase regulation of oligodendrocyte differentiation with CREB as a
      potential target.
AB  - Despite a substantial understanding of the factors regulating oligodendrocyte
      differentiation, the signaling mechanisms involved in this process are not well
      understood. This study elaborates on the findings (Bhat NR, Zhang P (1997) FASEB
      J 11:A925; Baron W, Metz B, Bansal R, Hoekstra D, de Vries H (2000) Mol Cell
      Neurosci 15:314-329) of a role for p38 MAP kinase signaling in oligodendrocyte
      differentiation and myelin gene expression. When proliferating oligodendrocyte
      progenitors were switched to a growth factor-free differentiation medium, there
      was a rapid activation of p38 kinase that correlated with an increased
      phosphorylation of CREB, a down-stream target and a factor involved in
      oligodendrocyte differentiation. Addition of forskolin, a known inducer of
      intracellular c-AMP and of oligodendrocyte differentiation, also stimulated CREB
      phosphorylation in a p38 kinase dependent way. Pharmacological inhibition of p38
      interfered with the morphological and antigenic changes associated with
      differentiating oligodendrocytes as well as with the developmental and forskolin
      induced expression of myelin basic protein, thereby supporting an essential role
      for p38 MAPK pathway in oligodendrocyte differentiation.

PMID- 17235688
TI  - High incidence of morphological myelodysplasia and apoptotic bone marrow cells in
      Behcet's disease.
AB  - Behcet's disease (BD) is a systemic inflammatory disorder of unknown etiology,
      and rarely complicated with myelodysplastic syndrome (MDS). In the present study,
      we investigated the morphological myelodysplasia and apoptotic rate of bone
      marrow cells in 15 patients with BD in comparison with MDS patients.
      Morphological myelodysplasia of bone marrow cells was detected in 53.3% of BD,
      but none showed chromosomal abnormalities. The apoptotic rate in BD patients
      (26.1 +/- 8.4%) was significantly higher in normal controls (11.3 +/- 2.4%; p <
      0.005) and significantly lower in patients with MDS (50.8 +/- 14.0%; p < 0.0001).
      These findings suggest that myelodysplasia in patients with BD is more frequent
      than expected, and possibly due to excess induction of apoptosis of bone marrow
      cells in BD. However, the rate of apoptotic bone marrow cells is lower than MDS,
      which may explain the slight peripheral cytopenia in BD, distinct from that in
      MDS.

PMID- 17235687
TI  - The role of anti-alpha-enolase autoantibodies in pathogenicity of autoimmune
      mediated retinopathy.
AB  - Autoantibodies against alpha-enolase, a glycolytic enzyme, have been frequently
      associated with visual loss and retinal degeneration in patients with autoimmune
      and cancer-associated retinopathy; however their role in the pathogenicity of
      retinopathy has not been fully explained. Thus, we examined the causative role of
      anti-enolase antibodies on retinal cells. In the in vitro studies reported here,
      we found that Enol-1 monoclonal antibody against alpha-enolase significantly
      inhibited the catalytic function of enolase, which resulted in the depletion of
      glycolytic ATP. Enol-1 significantly increased intracellular Ca(2+), which led to
      Bax translocation to the mitochondria, and the release of cytochrome c into the
      cytoplasm--events that correlated with the initiation of apoptosis. Normal IgG
      did not induce intracellular calcium or reduce cytosolic ATP. L-type voltage
      gated calcium channel blockers (nifedipine, D-cis-diltiazem, and verapamil) were
      effective in blocking the Ab-induced intracellular Ca(2+) rise and induction of
      Bax. Based on these findings we propose that chronic access of autoantibodies to
      the retina results in the inhibition of enolase catalytic function, depletion of
      ATP, and elevation in intracellular Ca(2+), leading to deregulation of glycolysis
      in retinal neurons and their destruction.

PMID- 17235689
TI  - Efficacy and tolerability of an argentine intravenous immunoglobulin in pediatric
      patients with primary immunodeficiency diseases.
AB  - Inmunoglobulina G Endovenosa UNC is a 5% liquid Argentine intravenous
      immunoglobulin obtained from South American donors. This prospective trial was
      designed to evaluate if the product meets the minimal efficacy requirement of the
      US Food and Drug Administration of <1 serious infection/subject/year as well as
      its safety in pediatric patients with Primary Immunodeficiency Diseases. Thirty
      patients under the age of 18, with well-defined Primary Immunodeficiency Diseases
      received Inmunoglobulina G Endovenosa UNC (330-700 mg/kg every 3-4 weeks) for 6
      months. Vital signs, laboratory abnormalities, adverse events and viral tests
      were assessed to evaluate safety. Two serious infections occurred (pneumonia and
      bacteriemia). The estimated infection rate was 0.114 serious
      infection/subject/year (95% CI, 0.003-0.2277). Minor adverse events occurred in
      5.5% of infusions; fever and headache were the most common. Neither severe
      adverse events, nor abnormal laboratory values were observed. All viral
      assessments were negative. Inmunoglobulina G Endovenosa UNC meets the minimal
      efficacy requirement of the US Food and Drug Administration for pediatric Primary
      Immunodeficiency Diseases patients and showed efficacy and safety data comparable
      with other data published.

PMID- 17235691
TI  - AMPA and kainate receptors in turtle retina: an immunocytochemical study.
AB  - 1. Glutamate is one of the main neurotransmitters in the retina. Its effects are
      mediated by a large number of ionotropic and metabotropic receptors.2. The
      distribution of ionotropic AMPA receptor subunits GluR1-4, kainate receptor
      subunits GluR5-7 and KA2, as well as delta receptors 1-2 was studied in turtle
      retina. Indirect immunofluorescence was used to localize the different receptor
      subunits viewed using light microscopy.3. Results show that all subunits, with
      exception of GluR1 and GluR5, are widely distributed in the turtle retina.4. They
      are mainly located in the both plexiform layers of the retina where punctate
      staining, a sign for synaptic localization, is observed.5. The vast majority of
      the subunits possess specific pattern of staining that allow to suppose that they
      are involved in different retinal circuits.6. It can be assumed that the GluR2/3
      and GluR6/7 subunits are expressed on the dendrites of a subpopulation of bipolar
      cells that are immunopositive for alpha-isoform of protein kinase C (PKCalpha).
      The GluR2/3 and GluR6/7 subunits are most probably used by the same PKCalpha
      immunopositive bipolar cells in their synaptic contacts with the third-order
      retinal neurons, the amacrine and ganglion cells.

PMID- 17235690
TI  - Induction of oxidative stress by chronic and acute glutaric acid administration
      to rats.
AB  - : 1. Glutaric acidemia type I (GA I) is a neurometabolic disorder caused by
      deficiency of glutaryl-CoA dehydrogenase, which leads to tissue accumulation of
      predominantly glutaric acid (GA) and also 3-hydroxyglutaric acid to a lesser
      amount. Affected patients usually present progressive cortical atrophy and acute
      striatal degeneration attributed to the toxic accumulating metabolites.2. In the
      present study, we determined a number of oxidative stress parameters, namely
      chemiluminescence, thiobarbituric acid-reactive substances (TBA-RS), total
      antioxidant reactivity (TAR), glutathione (GSH) levels, and the activities of
      catalase and glutathione peroxidase (GPx), in various tissues from rats
      chronically exposed to GA or to saline (controls). High GA concentrations,
      similar to those found in glutaric aciduria type I, were induced in the brain by
      three daily subcutaneous injections of saline-buffered GA (5 micromol/g body
      weight) to Wistar rats of 5-22 days of life. The parameters were assessed 12 h
      after the last GA administration in different brain structures, skeletal muscle,
      heart, liver, erythrocytes, and plasma. The lipid peroxidation parameters
      chemiluminescence and/or TBA-RS measurements were found significantly increased
      in midbrain, liver, and erythrocytes of GA-injected rats. The activity of GPx was
      significantly reduced in midbrain and markedly increased in liver. TAR
      measurement was significantly reduced in midbrain and liver. Furthermore, GSH
      levels were reduced in liver and heart. We also investigated the acute in vivo
      effect of GA administration on the same oxidative stress parameters in cerebral
      structures and erythrocytes from 22-day-old rats. We found that TBA-RS values
      were significantly increased in erythrocytes, TAR levels were markedly decreased
      in midbrain and cerebellum, and GPx activity mildly reduced in the midbrain.3.
      These data showing an imbalance between antioxidant defences and oxidative
      damage, particularly in midbrain, liver, and erythrocytes from GA-injected rats,
      indicate that oxidative stress might be involved in GA toxicity and that the
      midbrain, where the striatum is located, is the brain structure more susceptible
      to GA chronic and acute exposition.

PMID- 17235692
TI  - Depressing effect of caffeine at crayfish neuromuscular synapses II. Initial
      search for possible sites of action.
AB  - Caffeine's unexpected depression of synaptic transmission in the superficial
      flexor muscle system (SFM) of Procambarus clarkii was studied by looking at three
      known sites of action of this drug: via adenosine and ryanodine receptors and
      inhibition of phosphodiesterase.1. JPs did not change in size when exposed to
      physiological concentrations of adenosine, suggesting that the SFM system lacks
      presynaptic adenosine receptors.2. JPs slightly increased in size in the presence
      of a phosphodiesterase inhibitor, the opposite response to that obtained with
      caffeine, suggesting that caffeine is not acting via this pathway.3. A calcium
      ionophore immediately enhanced synaptic transmission in the SFM system but when
      given in combination with caffeine the enhancement is reduced and declines over
      time.4. Serotonin enhanced synaptic transmission in the SFM system, but when
      given in combination with caffeine this enhancement was not observed.5. These
      caffeine effects are interpreted in terms of alterations to the calcium
      homeostatic mechanisms of the terminals.

PMID- 17235693
TI  - Hippocampal CA1 pyramidal cell size is reduced in bipolar disorder.
AB  - 1. Schizophrenia and bipolar disorder are neurodevelopmental disorders with
      significant genetic vulnerabilities. Several trophic genes and/or proteins have
      been implicated in the causation for both disorders.2. We hypothesized that these
      genes and/or proteins may impact neuronal growth in both disorders.3. Hippocampal
      tissue sections from CA1 area of schizophrenic, bipolar, depressed, and controls
      subjects, matched for age, sex, PMI, drug exposure, and brain pH were prepared
      for cell size determination using the Stanley Medical Research Foundation
      postmortem brain collection.4. Quantification of hippocampal CA1 pyramidal neuron
      size showed a significant 12% reduction in cell size (p < 0.05) in bipolar
      subjects vs. controls. There were nonsignificant trends for reduction in cell
      size in both schizophrenic and depressed subjects vs. controls.5. These results
      indicate for the first time that pyramidal cell atrophy is present in hippocampus
      of subjects with bipolar disorder.

PMID- 17235694
TI  - Chelating compound, chrysoidine, is more effective in both antiprion activity and
      brain endothelial permeability than quinacrine.
AB  - 1. As an extension of our previous study of quinacrine and its derivatives,
      chelating chemicals were screened to obtain more effective, better brain
      permeable antiprion compounds using either prion-infected neuroblastoma cells or
      brain capillary endothelial cells.2. Eleven chemicals were found to have
      antiprion activity. Most of them shared a common structure consisting of benzene
      or naphthalene at either end of an azo bond. Structure-activity data suggest that
      chelating activity is not necessary but might contribute to the antiprion
      action.3. Chrysoidine, a representative compound found here, was about 27 times
      more effective in the antiprion activity and five times more efficiently
      permeable through the brain capillary endothelial cells than quinacrine was.4.
      These chemicals might be useful as compounds for development of therapeutics for
      prion diseases.

PMID- 17235695
TI  - Heterogeneous distribution of kir3 potassium channel proteins within dopaminergic
      neurons in the mesencephalon of the rat brain.
AB  - 1. Dopaminergic neurons in the substantia nigra pars compacta (SNc) and the
      ventral tegmental area (VTA) of the ventral mesencephalon play an important role
      in the regulation of the parallel basal ganglia loops.2. We have raised affinity
      purified polyclonal rabbit antibodies specific for all four members of the Kir3
      family of inwardly rectifying potassium channels (Kir3.1-Kir3.4) to investigate
      the distribution of the channel proteins in the dopaminergic neurons of the rat
      mesencephalon at light and electron microscopic level. In addition,
      immunocytochemical double labeling with tyrosine hydroxylase (TH), a marker of
      dopaminergic neurons, were performed.3. All Kir3 channels were present in this
      region. However, the individual proteins showed differential cellular and
      subcellular distributions.4. Kir3.1 immunoreactivity was found in SNc fibers and
      some neurons of the substantia nigra pars reticulata (SNr). Few Kir3.3-positive
      neurons were found in the SNc. However, a strong Kir3.3 signal was identified in
      the SNr neuropil. Weak Kir3.4 staining was detected in neuronal somata as well as
      in dendritic fibers of both parts of the SN.5. In the VTA, Kir3.1, Kir3.3, and
      Kir3.4 showed only weak staining of neuropil structures. The distribution of the
      Kir3.2 channel protein was especially striking with strong labeling in the SNc
      and in the lateral but not central VTA.6. Our results suggest that the
      heterogeneously distributed Kir3.2 channel proteins could help to discriminate
      the dopaminergic neurons of VTA and SNc.

PMID- 17235697
TI  - Referral to consumer-run programs by mental health providers: a national survey.
AB  - This study describes mental health providers' awareness of, attitudes toward, and
      likelihood to refer to consumer-run programs. A mail survey method was used with
      a total of 301 questionnaires returned (33.5% response rate) from a national
      random sample. Findings suggest that providers believe consumers are able to
      provide effective mental health services, yet have less confidence in consumer
      run programs. Slightly over half of the providers were aware of consumer-run
      programs and fewer had made referrals. Providers in non-public settings, agencies
      that hire consumers as providers, and agencies that collaborate with consumer-run
      programs were more likely to have made referrals. To maximize available community
      supports for service recipients, providers should consider newer, consumer-run
      service technologies.

PMID- 17235698
TI  - The Trauma Recovery Group: a cognitive-behavioral program for post-traumatic
      stress disorder in persons with severe mental illness.
AB  - To address the problem of post-traumatic stress disorder (PTSD) in severe mental
      illness, the Trauma Recovery Group, a mixed gender cognitive-behavioral program,
      was developed and piloted at a community mental health center. The 21-week
      program includes breathing retraining, education about PTSD, cognitive
      restructuring, coping with symptoms, and making a recovery plan. Eighty clients
      were assessed at baseline and 41 provided follow-up data. Retention in the group
      was good: 59%. Treatment completers improved significantly in PTSD symptoms and
      diagnosis, depression, and post-traumatic cognitions, but dropouts did not. The
      results support the feasibility of the program and suggest it produces clinical
      benefits.

PMID- 17235700
TI  - Strategic behavior in adolescent sexual offenses against children: linking modus
      operandi to sexual behaviors.
AB  - In this paper, the modus operandi of 103 adolescents involved in sexual offenses
      against children (12 year old or less) is analyzed. Modus operandi strategies
      were measured by the participants' responses to the Modus Operandi Questionnaire.
      Findings indicate that the degree of intrusiveness of the sexual behaviors
      committed by the adolescents is contingent on the participation of their victims
      during the sexual episodes. Moreover, the more strategic adolescents may be more
      likely to secure compliance. This study shows the relevance of analyzing
      adolescent modus operandi as purposeful behavior and discusses some implications
      of the findings for crime-commission or offending process models.

PMID- 17235699
TI  - Psychiatrists' smoking cessation activities with Ohio community mental health
      center patients.
AB  - This study describes a survey of Ohio community mental health center
      psychiatrists' perceptions and practices regarding smoking cessation activities
      using the 5A's method of smoking cessation. Of the 150 psychiatrists surveyed, 80
      (53%) were returned. The majority of psychiatrists reported asking their patients
      about cigarette smoking status as well as giving advice to quit. However, the
      practice of actually facilitating quit attempts (i.e. with social support,
      nicotine replacement therapy, referrals, and follow-up visits) was lacking. This
      demonstrates that although cigarette smoking in individuals with mental illness
      is recognized as a major problem by adult psychiatrists, too little is being done
      to adequately address the issue.

PMID- 17235701
TI  - Increasing honest responding on cognitive distortions in child molesters: the
      bogus pipeline revisited.
AB  - Questionnaires are relied upon by forensic psychologists, clinicians,
      researchers, and social services to assess child molesters' (CMs') offense
      supportive beliefs (or cognitive distortions). In this study, we used an
      experimental procedure to evaluate whether extrafamilial CMs underreported their
      questionnaire-assessed beliefs. At time one, 41 CMs were questionnaire-assessed
      under standard conditions (i.e., they were free to impression manage). At time
      two, CMs were questionnaire-assessed again; 18 were randomly attached to a
      convincing fake lie detector (a bogus pipeline), the others were free to
      impression manage. The results showed that bogus pipeline CMs significantly
      increased cognitive distortion endorsements compared to their own previous
      endorsements, and their control counterparts' endorsements. The findings are the
      first experimental evidence showing that CMs consciously depress their scores on
      transparent questionnaires.

PMID- 17235696
TI  - The relevance of neuroactive steroids in schizophrenia, depression, and anxiety
      disorders.
AB  - 1. Neuroactive steroids are steroid hormones that exert rapid, nongenomic effects
      at ligand-gated ion channels. There is increasing awareness of the possible role
      of these steroids in the pathology and manifestation of symptoms of psychiatric
      disorders. The aim of this paper is to review the current knowledge of
      neuroactive steroid functioning in the central nervous system, and to assess the
      role of neuroactive steroids in the pathophysiology and treatment of symptoms of
      schizophrenia, depression, and anxiety disorders. Particular emphasis will be
      placed on GABAA receptor modulation, given the extensive knowledge of the
      interactions between this receptor complex, neuroactive steroids, and psychiatric
      illness. 2. A brief description of neuroactive steroid metabolism is followed by
      a discussion of the interactions of neuroactive steroids with acute and chronic
      stress and the HPA axis. Preclinical and clinical studies related to psychiatric
      disorders that have been conducted on neuroactive steroids are also described. 3.
      Plasma concentrations of some neuroactive steroids are altered in individuals
      suffering from schizophrenia, depression, or anxiety disorders compared to values
      in healthy controls. Some drugs used to treat these disorders have been reported
      to alter plasma and brain concentrations in clinical and preclinical studies,
      respectively. 4. Further research is warranted into the role of neuroactive
      steroids in the pathophysiology of psychiatric illnesses and the possible role of
      these steroids in the successful treatment of these disorders.

PMID- 17235702
TI  - The validity of phallometric assessment with rapists: comments on Looman &
      Marshall (2005).
AB  - In a recent article Looman and Marshall (2005) questioned the validity of
      phallometric assessment of rapists based on the results of a study of
      incarcerated rapists and child molesters. In this commentary we offer (1) a
      critique of the methods used and conclusions reached by Looman and Marshall and
      (2) a discussion of important methodological issues relevant to phallometry. We
      conclude that the correct inference from Looman and Marshall's study is that
      rapists, as a group, show a pattern of sexual arousal to audiotaped scenarios of
      coercive and non-coercive sex that significantly differs from the pattern of
      groups of non-sex offenders, in agreement with the general literature on this
      question.

PMID- 17235703
TI  - A model of NO/O2 transport in capillary-perfused tissue containing an arteriole
      and venule pair.
AB  - The goal of this study was to investigate the complex co-transport of nitric
      oxide (NO) and oxygen (O2) in a paired arteriole-venule, surrounded by capillary
      perfused tissue using a computer model. Blood flow was assumed to be steady in
      the arteriolar and venular lumens and to obey Darcy's law in the tissue. NO
      consumption rate was assumed to be constant in the core of the arteriolar and
      venular lumen and to decrease linearly to the endothelium. Average NO consumption
      rate by capillary blood in a unit tissue volume was assumed proportional to the
      blood flux across the volume. Our results predict that: (1) the capillary bed,
      which connects the arteriole and venule, facilitates the release of O2 from the
      vessel pair to the surrounding tissue; (2) decreasing the distance between
      arteriole and venule can result in a higher NO concentration in the venular wall
      than in the arteriolar wall; (3) in the absence of capillaries in the surrounding
      tissue, diffusion of NO from venule to arteriole contributes little to NO
      concentration in the arteriolar wall; and (4) when capillaries are added to the
      simulation, a significant increase of NO in the arteriolar wall is observed.

PMID- 17235704
TI  - Prevalence of silent celiac disease in patients with dyspepsia.
AB  - Celiac disease (CD) has become more common than in the past, although it
      frequently remains undetected for long periods of time. One reason for this is
      failure by health care professionals to recognize the variable clinical
      manifestations of CD and to perform the appropriate tests to make the diagnosis.
      Although dyspepsia may be part of a clinical spectrum in CD patients, there are
      scarce data about its prevalence in silent CD. We aimed to determine the
      prevalence of CD in otherwise healthy dyspeptic patients by means of serologic
      screening followed by endoscopic biopsies if appropriate. Anti-endomysium
      antibody assay was positive in 3 of 196 patients. All 3 were female, ages ranged
      from 19-52 years (mean +/- SD age, 36 +/- 16 years). Duodenal biopsies were
      compatible with CD in all, whereas abnormal endoscopic findings were noted in 2.
      Therefore, a 1.5% prevalence of CD was observed in this study group. The odds
      ratio for CD was 2.57 (95% confidence interval) in comparison with the general
      population. CD should be kept in mind as a cause of dyspepsia during clinical
      activities. The association between these 2 conditions is, at most, weak, but a
      gluten-free diet may still bring symptomatic relief for dyspeptic symptoms in CD.
      During endoscopic examination for dyspepsia, if indicated, endoscopists should
      carefully inspect the duodenum for CD findings. Although routine serologic
      screening can not be recommended, it may be appropriate for the patients with
      refractory dyspepsia, especially females.

PMID- 17235705
TI  - Octreotide/Midodrine therapy significantly improves renal function and 30-day
      survival in patients with type 1 hepatorenal syndrome.
AB  - Type 1 hepatorenal syndrome (HRS) can be a rapidly fatal consequence of liver
      failure. Recent studies have utilized vasoconstrictor therapies to combat
      splanchnic vasodilatation. We aimed to evaluate the efficacy of a promising
      treatment for type 1 HRS. We compared the survival of HRS patients who received
      octreotide and midodrine treatment at Rancho Los Amigos Medical Center with a
      concurrent untreated control group of HRS patients who did not receive this
      treatment. Of the 81 patients, 60 were treated with octreotide/midodrine and 21
      were controls. Mortality was significantly lower in the treatment group (43%)
      than in the controls (71%; P < 0.05). Furthermore, 24 study patients (40%) had a
      sustained reduction of serum creatinine compared with only 2 controls (10%; P <
      0.05). This large retrospective study suggests that octreotide/midodrine
      treatment appears to improve 30-day survival. A randomized, controlled trial is
      the next important step toward evaluating this treatment modality.

PMID- 17235706
TI  - The role of probiotics in inflammatory bowel disease.

PMID- 17235707
TI  - Age-related variation of intraepithelial lymphocytes subsets in normal human
      duodenal mucosa.
AB  - The enumeration of intestinal intraepithelial lymphocytes (IELs), and the
      phenotyping of CD3+CD 103+ (TcRalphabeta, TcRgammadelta) and CD3-CD103+ IEL
      subsets constitute useful diagnostic tools for the correct interpretation of the
      mucosal histology of duodenal/jejunal biopsies in many pathological conditions of
      the small intestine, particularly celiac disease (CD). This work evaluates the
      ranges of duodenal IEL counts by flow cytometry in healthy mucosa from pediatric
      and adult controls, establishing normal reference values for CD3+ TcRgammadelta
      and CD3- subsets and their variation with age. Seventy-four pediatric controls
      and 36 adult controls were identified on the basis of their normal histology from
      more than 1,000 duodenal diagnostic biopsies performed in Caucasian subjects.
      Total IEL counts and IEL subsets ("IEL lymphogram") were analyzed by four-color
      flow cytometry (FCM). IEL represent 7.7% +/- 0.4 (mean +/- SE) and 8.5% +/- 0.5
      of the cells isolated from the epithelium in the pediatric and adult series,
      respectively. The upper normal range, considered as the 97 percentile, is 14% in
      pediatrics and 15% in adults. No significant difference was observed between
      TcRgammadeltaIEL percentages in children (6.9% +/- 0.5 of the total IELs) and
      adults (6.6% +/- 0.8). However, the density of CD3- IELs is significantly higher
      (p < 0.001) in the mucosa from controls under 3 years (50.2% +/- 2.6) than in
      adults (25.5% +/- 2.1). IEL lymphogram by flow cytometry is an easy, quick and
      reliable analysis performed in one of the biopsy specimens obtained during a
      diagnostic endoscopy, and confers specificity to the histopathological findings.
      IEL counts below 14% in children and 15% in adults should be considered within a
      normal range in the evaluation of duodenal mucosa by FCM. No differences with age
      were observed with respect to TcRgammadeltaIEL, while the CD3- IEL fraction was
      significantly higher on children under 3 years, with a trend to increase again in
      the elderly.

PMID- 17235709
TI  - Energetically plausible model of a self-maintaining protocellular system.
AB  - Most of the models for cellular origin stress one of these two approaches:
      "replication-first" or "metabolism-first." The model presented here focuses on
      the latter, consisting of the combination of kinetic and energetic descriptions
      of protocellular metabolism. In this model, the membrane plays a very crucial
      role in the maintenance of the cell and the osmotic stability. The model contains
      the following elements: structural membrane elements (Lm), transducers (T),
      molecules (E) that combine enzyme-like activity with the transport of elements
      through the membrane, energy-rich molecules (A), precursors of each type of
      molecule (l, t, e, and a, respectively), and an impermeable substance (x).
      Different kinetic parameters lead to a wide region of stable steady states, as
      studied through numerical analysis. The system presents stability under different
      external conditions. Two energy source regimes have been studied: periodic and
      nonperiodic. The kinetic restrictions that lead to osmotic stability are also
      addressed in this paper.

PMID- 17235708
TI  - Dynamics of vaccination strategies via projected dynamical systems.
AB  - Previous game theoretical analyses of vaccinating behaviour have underscored the
      strategic interaction between individuals attempting to maximise their health
      states, in situations where an individual's health state depends upon the
      vaccination decisions of others due to the presence of herd immunity. Here, we
      extend such analyses by applying the theories of variational inequalities (VI)
      and projected dynamical systems (PDS) to vaccination games. A PDS provides a
      dynamics that gives the conditions for existence, uniqueness and stability
      properties of Nash equilibria. In this paper, it is used to analyse the dynamics
      of vaccinating behaviour in a population consisting of distinct social groups,
      where each group has different perceptions of vaccine and disease risks. In
      particular, we study populations with two groups, where the size of one group is
      strictly larger than the size of the other group (a majority/minority
      population). We find that a population with a vaccine-inclined majority group and
      a vaccine-averse minority group exhibits higher average vaccine coverage than the
      corresponding homogeneous population, when the vaccine is perceived as being
      risky relative to the disease. Our model also reproduces a feature of real
      populations: In certain parameter regimes, it is possible to have a majority
      group adopting high vaccination rates and simultaneously a vaccine-averse
      minority group adopting low vaccination rates. Moreover, we find that minority
      groups will tend to exhibit more extreme changes in vaccinating behaviour for a
      given change in risk perception, in comparison to majority groups. These results
      emphasise the important role played by social heterogeneity in vaccination
      behaviour, while also highlighting the valuable role that can be played by PDS
      and VI in mathematical epidemiology.

PMID- 17235710
TI  - A model of tracer transport in airway surface liquid.
AB  - This study is concerned with reconciling theoretical modelling of the fluid flow
      in the airway surface liquid with experimental visualisation of tracer transport
      in human airway epithelial cultures. The airways are covered by a dense mat of
      cilia of length approximately 6 microm beating in a watery periciliary liquid
      (PCL). Above this there is a layer of viscoelastic mucus which traps inhaled
      pathogens. Cilia propel mucus along the airway towards the trachea and mouth.
      Theoretical analyses of the beat cycle (smith et al., 2006b; Fulford and Blake,
      1986) predict small transport of PCL compared with mucus, based on the assumption
      that the epithelium is impermeable to fluid. However, an experimental study
      (Matsui et al., 1998) indicates nearly equal transport of PCL and mucus. Building
      on existing understanding of steady advection-diffusion in the ASL (Blake and
      Gaffney, 2001; Mitran, 2004), numerical simulation of an advection-diffusion
      model of tracer transport is used to test several proposed flow profiles and to
      test the importance of oscillatory shearing caused by the beating cilia. A
      mechanically derived oscillatory flow with very low mean transport of PCL results
      in relatively little 'smearing' of the tracer pulses. Other effects such as
      mixing between the PCL and mucus, and significant transport in the upper part of
      the PCL above the cilia tips are tested and result in still closer transport,
      with separation between the tracer pulses in the two layers being less than 9%.
      Furthermore, experimental results may be replicated to a very high degree of
      accuracy if mean transport of PCL is only 50% of mucus transport, significantly
      less than the mean PCL transport first inferred on the basis of experimental
      results.

PMID- 17235711
TI  - Surgery as a bridge to palliative chemotherapy in patients with malignant bowel
      obstruction from colorectal cancer.
AB  - BACKGROUND: Malignant bowel obstruction (MBO) is a feature of the clinical course
      of 10-28% of colorectal cancer (CRC) patients and is associated with a poor
      prognosis. Recent advancements in palliative chemotherapy regimens have prolonged
      survival in patients with stage IV CRC. Few reports exist that describe outcomes
      in patients who have had surgery for MBO and subsequent chemotherapy as part of
      their treatment. The objective of this study was to review surgical outcomes in
      patients with MBO for CRC and to evaluate the extent to which surgery can serve
      as a bridge to palliative chemotherapy. METHODS: Patients who presented with MBO
      and had surgical treatment were identified from a prospectively kept database at
      a single tertiary care center between 09/99 and 08/04. Charts were
      retrospectively reviewed and clinical and outcomes data were abstracted. RESULTS:
      Forty-seven patients were identified who had surgery as part of the treatment for
      MBO from CRC. Operations included resections, bypasses and stoma creation.
      Overall, 80% of patients were able to tolerate solid food post-operatively and
      return home. The median survival for the entire cohort was 3.5 months. Seven
      patients died within 30 days of surgery. Of the remainder, 24 patients were
      palliated with surgery alone and 16 patients ultimately received palliative
      chemotherapy. Survival in the final cohort was significantly prolonged (P <
      0.001). CONCLUSION: Surgery can adequately palliate a substantial proportion of
      patients with MBO from CRC with acceptable morbidity and mortality. In addition,
      in a subset of patients it can facilitate palliative chemotherapy that is
      associated with improved overall survival.

PMID- 17235712
TI  - Comorbidity is a prognostic factor in elderly patients with head and neck cancer.
AB  - BACKGROUND: The number of aged patients with head and neck cancer is increasing.
      Comorbidities are common in this population. It is necessary to evaluate the
      effect of comorbidities as measured with the ACE-27 index on recurrence and
      survival of elderly patients with head and neck cancer, adjusting by other
      prognostic factors as age, clinical stage and functional status index. PATIENTS:
      Three hundred and ten patients greater than 70 years of age with head and neck
      cancer in a referral cancer center were studied. Comorbidity measured with the
      ACE-27 index was the main independent variable. The outcomes were recurrence and
      survival. RESULTS: Comorbidities were present in 75% of patients. Five-year
      disease-free survival, overall survival and cancer-specific survival were 63.1,
      42.8 and 55.8%, respectively. Advanced clinical stage and Karnofsky index < or
      =70 were associated with recurrence. Age >80 years, male gender, Karnofsky index
      < or =80, advanced clinical stage, and ACE value > or =2 were independently
      associated with overall survival. The ACE-27 value was not associated with cancer
      specific survival. The Karnofsky performance index was associated with overall
      survival and mortality and acted as a confounding factor on multivariable
      analysis on overall and cancer-specific survival. CONCLUSIONS: Comorbidity
      measured with ACE-27 was a prognostic factor for overall survival in patients
      older than 70 years with head and neck cancer. The Karnofsky performance index
      could be included in multivariable analysis of survival for older patients with
      head and neck cancer.

PMID- 17235713
TI  - Treatment of the adenocarcinoma of the esophagogastric junction at a single
      institution in Mexico.
AB  - BACKGROUND: Adenocarcinoma of the esophagogastric junction (EGJ) is rapidly
      increasing in the west. Our aim is to define the prognostic factors and treatment
      of EGJ carcinoma in Mexico, particularly the location after the Siewert's
      classification. METHODS: A retrospective cohort of patients suffering from EGJ
      adenocarcinoma treated from 1987 to 2000. The Kaplan-Meier and the Cox's models
      were used to define prognostic factors. RESULTS: Two hundred and thirty-four
      patients were included, 90 females and 144 males. Surgical resection was possible
      in 68 cases only (29%). Significant prognostic factors were tumor node metastasis
      (TNM) stage [stages I-II: risk ratio (RR) is 1; stage III RR is 1.3, 95%
      confidence interval (CI) 0.75-2.4; stage IV RR, 2.04, 95% CI 1.1-3.7], gender
      (male RR = 1.47, 95% CI 1.05-2.05), metastatic lymph node ratio (no resection: RR
      = 1; ratio 0.2-1 RR=0.67, 95% CI 0.39-1.14; ratio 0-0.19 RR = 0.42, 95% CI 0.23
      0.76) and seralbumin (3 mg/dL or less RR = 2.05 95% CI 1.3-3.2; 3.1-3.4 mg/dL RR
      = 1.9 95% CI 1.2-3.03; 3.5-3.8 mg/dL RR = 1.3 95% CI 0.8-1.9; 3.9 mg/dL or more:
      RR = 1) (model P = 0.0001). CONCLUSIONS: EGJ adenocarcinoma is a highly lethal
      neoplasia and the location after the Siewert' classification is not a prognostic
      factor. In Mexico, TNM clinical stage, serum albumin, gender, surgical resection
      and metastatic lymph node ratio are significant prognostic factors. Curative
      treatment is infrequent but radical resection is associated to longer survival.
      Consequently, the management must consider quality of life and surgical
      morbidity.

PMID- 17235714
TI  - Antitumor effect of gemcitabine on orthotopically inoculated human gallbladder
      cancer cells in nude mice.
AB  - BACKGROUND: The prognosis of gallbladder carcinoma is poor; therefore,
      investigating the efficacy of new chemotherapy agents is essential for the
      treatments for this tumor. Recently, several studies have reported clinical
      trials using gemcitabine as treatment for advanced gallbladder cancers. However,
      the antitumor effects of gemcitabine on gallbladder carcinoma have not been
      examined in in vitro and in vivo model systems. METHODS: We examined the
      cytotoxicity of gemcitabine in four biliary tract cancer cell lines using the WST
      1 assay. In addition, we examined the effect of gemcitabine on gallbladder
      cancers resulting from orthotopic inoculation of NOZ gallbladder tumor cells into
      nude mice. One week after transplantation, the mice were randomized into two
      groups: In Group A, the mice were treated by an intra-peritoneal injection of
      0.9% sodium chloride for three weeks after inoculation (control). In Group B, the
      mice were treated by an intra-peritoneal injection of gemcitabine (125 mg / kg)
      for three weeks. All mice were sacrificed one week after the end of treatment,
      and macroscopic and histological findings were evaluated. The expression levels
      of proliferating-cell nuclear antigen (PCNA) were examined to investigate
      cellular proliferation activity, and Tunnel assays were performed to determine
      apoptotic status. Survival duration of the mice after gemcitabine treatment was
      compared to that of untreated mice. RESULTS: The gemcitabine sensitivity of the
      four biliary tract cancer cell lines was similar in a dose dependent manner. In
      the in vivo models, the Group A mice showed huge tumors of the gallbladder, with
      liver invasion and lymph node metastases. However, there were no abdominal tumors
      in the Group B mice, and microscopic gallbladder cancer could only be detected
      from histological findings. The mean percent of PCNA-positive tumor cells was
      significantly higher in tumors from mice in Group A (71.9%) compared to those of
      Group B (34.7%). The mean percent of Tunnel-positive tumor cells was
      significantly lower in mice from Group A (2.0%) than those from Group B (5.7%).
      Survival duration was prolonged significantly in the gemcitabine-treated mice
      relative to untreated mice. CONCLUSIONS: Gemcitabine treatment may inhibit tumor
      progression and prolong survival in gallbladder cancer by inhibiting cell
      proliferation and inducing apoptosis.

PMID- 17235715
TI  - In vivo intraoperative radiotherapy: a novel approach to radiotherapy for early
      stage breast cancer.
AB  - INTRODUCTION: Intraoperative radiotherapy (IORT) has the potential to eliminate
      the access problems associated with standard 6-week post-operative external beam
      radiotherapy for patients with breast cancer. However, accurate delivery of the
      IORT dose for breast cancer has been problematic due to difficulty estimating the
      tumor bed after tumor removal and tissue re-approximation. We are investigating
      the feasibility of partial breast irradiation using a single fraction of IORT
      delivered to the tumor in vivo prior to surgical resection. METHODS: In a trial,
      approved by the University of North Carolina School of Medicine Institutional
      Review Board, patients > or =55 years old with infiltrating ductal carcinoma
      without an extensive intraductal component with an overall tumor size < or =3.0
      cm receive a single dose of IORT in place of standard post-operative
      radiotherapy. RESULTS: All patients undergo preoperative ultrasonography to
      define the target volume. In a standard operating room, the tumor is exposed
      through a standard partial mastectomy incision. IORT is then delivered using a
      mobile, self-shielded, magnetron-driven X-band linear accelerator (Intraop Corp,
      Santa Clara, CA, USA). 15 Gy is delivered to the 90% isodose line covering the
      tumor with a 1 cm margin anterior-posterior and 2 cm margins laterally. After
      IORT, partial mastectomy is performed in the usual manner. CONCLUSIONS: IORT for
      breast cancer, delivered to the exposed tumor in vivo, is feasible and allows
      accurate estimation of the tumor bed. Further follow-up is ongoing to determine
      the efficacy of this approach.

PMID- 17235716
TI  - Intraoperative digital specimen mammography: rapid, accurate results expedite
      surgery.
AB  - INTRODUCTION: Specimen mammography during image guided breast surgery is a daily
      occurrence. The process of specimen travel, imaging and reporting may take 20-30
      minutes. An intraoperative method to obtain digital specimen mammograms may
      expedite the process. We compared intraoperative digital specimen mammography
      (IDSM) as well as standard specimen mammography (SSM) on 121 consecutive image
      guided lumpectomies. METHODS: Each lumpectomy specimen had IDSM obtained followed
      by travel to radiology for SSM. Surgical decisions were based on all imaging
      obtained. Data included 1) the ability of each imaging method to identify the
      target lesion, 2) degree of concordance of surgical interpretation of IDSM
      compared to radiologist interpretation of SSM, 3) the time required from
      lumpectomy to surgical review of images from each method, and 4) potential
      operative time savings. RESULTS: Intraoperative digital specimen mammography
      (IDSM) was equally as accurate as standard x-ray film specimen mammography. There
      was no significant difference between 1) the frequency of identification of the
      target lesion by surgeon or radiologist, 2) lack of identification of any lesion,
      or 3) frequency of involved margins using imaging criteria. However, there was a
      marked difference in 1) the time needed to obtain images ready to read, 2) the
      ability to re-excise tissue promptly, and 3) the overall operating room time with
      an average decrease of 19 minutes. CONCLUSIONS: Intraoperative digital specimen
      mammography (IDSM) was equally accurate as SSM obtained in this study. Use of
      this new technology allows surgeons to quickly view specimen images which
      translate into shorter more efficient operations.

PMID- 17235718
TI  - Long-term characteristics of 5-year survivors after liver resection for
      colorectal metastases.
AB  - BACKGROUND: We investigated factors affecting 5-year survival in patients
      undergoing hepatic resection for colorectal cancer metastases, including events
      long after initial hepatectomy. Although retrospective studies have demonstrated
      survival benefit of hepatectomy for metastatic colorectal cancer, few have
      included sufficient 5-year survivors to identify survival-related factors
      throughout the clinical course. METHODS: We divided 156 patients with hepatectomy
      for colorectal cancer metastases into 5-year survivors (n = 64) and patients
      dying before 5 years after hepatectomy (n = 92). Clinicopathologic data were
      compared retrospectively with respect to long-term outcome. RESULTS: By
      multivariate analysis, large liver tumors (adjusted relative risk, 2.029; P =
      .011), short tumor doubling time (1.809; P = .026), and origin from poorly
      differentiated primary adenocarcinoma (12.632; P = .001) compromised survival,
      whereas initial treatment-related variables did not. Although no difference was
      seen in initial treatment-related variables between 5-year survivors with
      recurrence after hepatectomy and patients dying before 5 years, repeat surgery
      was used more frequently in survivors (P < .001), typically with adjuvant
      chemotherapy. CONCLUSIONS: Reoperations for each recurrence of metastases,
      followed by additional chemotherapy, frequently resulted in long survival.

PMID- 17235717
TI  - Gain of chromosome 8q: a potential prognostic marker in resectable adenocarcinoma
      of the pancreas?
AB  - BACKGROUND: The objective of this study was to identify genomic alterations in
      resectable pancreatic cancer (PCA). Chromosomal imbalances were correlated with
      histopathological and clinical data to verify their prognostic significance.
      METHODS: Specimens of 33 PCA were investigated by comparative genomic
      hybridization. Microdissection was used for separation of PCA from the normal
      cells before isolation of DNA; nick-end labeling and hybridization were performed
      according to standard protocols. Aberrations were correlated with staging and
      grading using log-rank test and Cox regression. Survival rates were plotted using
      the Kaplan-Meier method. RESULTS: Twenty-eight (85%) PCA showed aberrations.
      Gains of chromosomal material were most frequently identified on 8q (42%), 13q
      (30%), 18p (21%), and 3q (18%). Genetic losses were frequently detected on 1p
      (45%), 22 (42%), 19 (36%), 17p (27%), 18q and 8p (15% each), and 3p (12%). Losses
      of 8p (n = 5) and 3p (n = 4) were only detected in stages III and IV (P < 0.05).
      Median survival time of all patients was 13 months. Median survival time of
      patients with aberration of 8q (n = 14) was 8.5 months compared to 16 months in
      patients without gain of 8q (n = 19; P = 0.029). CONCLUSIONS: The chromosomal
      regions containing genetic alterations represent potential loci for new target
      genes in PCA. The significant correlation of gain of chromosome 8q with short
      survival time suggests that 8q may be a new marker to assess prognosis and
      malignant potential of resected PCA in the individual patient, thereby helping to
      identify patients at risk for recurrence that might profit from adjuvant therapy.

PMID- 17235719
TI  - Laparoscopic pelvic autonomic nerve-preserving surgery for patients with lower
      rectal cancer after chemoradiation therapy.
AB  - OBJECTIVE: This is a phase II study, the aim of which is to determine if a
      laparoscopic approach can be used in pelvic autonomic nerve-preserving surgery
      for patients with lower rectal cancer following chemoradiation therapy. METHODS:
      Patients with T3 lower rectal cancer treated by preoperative chemoradiation were
      recruited and subjected to laparoscopic pelvic autonomic nerve-preserving surgery
      with total mesorectal excision and a sphincter-saving procedure. This study was
      performed with the approval of the ethics committee of National Taiwan University
      Hospital. Because the quality of a surgical trial is highly dependent on the
      skill of the surgeon with respect to the technique under study, it is imperative
      that a surgical trial only be implemented after the surgical technique has been
      judged to be mature. Before the start of this clinical trial, we gained a sound
      knowledge of surgical anatomy through conventional open surgery for rectal cancer
      and mastered the related laparoscopic skills from other sound and proven
      laparoscopic approaches, including right hemicolectomy, left hemicolectomy, among
      others. We determined that the learning curve for this surgical technique
      necessitated that colorectal surgeons carry out at least 20 such procedures. At
      this point we conducted this clinical trial. The details of the surgical
      procedures have been shown in the attached video. Briefly, the dissection
      commences at the pelvic promontory with exposure and preservation of the superior
      hypogastric plexus. The pre-aortic plexus and inferior mesenteric plexus are
      preserved by sparing the pre-aortic connective tissue and leaving a 1- to 2-cm
      long stump of the inferior mesenteric artery in situ. Subsequently, the "holy
      plane" at the transition of the mesosigmoid to the mesorectum is meticulously
      dissected to progressively displace the hypogastric nerves dorsally and laterally
      and, therefore, preserving them. Following adequate dorsal and lateral dissection
      down to the floor of the pelvis, the so-called lateral ligament is reached at
      which the mesorectum appears to be adherent, anteriorly and laterally, to the
      inferior hypogastric plexus (at roughly 10:00-2:00 O'clock or within an angle of
      60 degrees about symphysis on both sides). The ligaments are divided immediately
      at the endopelvic fascia of the mesorectum to avoid damage to the inferior
      hypogastric plexus (pelvic plexus). Finally, great care was taken to dissect the
      lateral border of Denonvilliers' fascia where the inferior hypogastric plexus
      joins the neurovascular bundle described by Walsh. Postoperatively, only patients
      successfully operated on by total pelvic autonomic nerve-preserving surgery were
      included in the statistical analysis of surgical outcomes. Preoperatively, all
      patients were screened for their genitourinary function by a questionnaire-based
      interview. Patients with abnormal preoperative baseline functional data were
      excluded from further postoperative assessment of sexual or urinary function. The
      male sexual function was evaluated by potency and ejaculation. In female
      patients, the sexual function was assessed by vaginal lubrication, dyspareunia,
      sexual arousal, and orgasm. The reason for these four parameters is because the
      influence of pelvic autonomic nerve damage on female sexual function has been
      ambiguous but would most likely result in impairment of vaginal lubrication and
      congestion of the genitals. We evaluated sexual function at 6 months
      postoperatively, when the temporary colostomy had been closed and the patients
      were completely recovered from surgical disability. In evaluating urinary
      function, the duration between initial voiding trial and spontaneous voiding was
      recorded. The questionnaire used for the assessment of urinary dysfunction was
      based on the International Prostate Symptom Score and the following parameters
      from this Score were used: incomplete emptying, frequency, intermittency,
      urgency, week stream, straining, and nocturia. Any voiding problems recovered
      within 3 months after the operation were considered to be transient bladder
      voiding dysfunction; all other voiding problems were deemed persistent. The
      interview and scoring of the questionnaire were done by the research assistant
      blinded to operation procedures. The genitourinary function was ranked as good,
      fair (decreased), and poor (impaired). RESULTS: Between June 2003 and December
      2005, a total of 98 patients (stage II: n = 44; stage III: n = 54; male: n = 50;
      female: n = 48) were enrolled in this study. Technically, although the dissection
      plane is a little blurred by preoperative chemoradiation therapy, the
      laparoscopic pelvic nerve-preserving procedure with total mesorectal excision was
      successfully performed in 89 (90.8%) patients with an acceptable operation time
      (284.4 +/- 44.8 minutes; mean +/- standard deviation) and little blood loss
      (114.5 +/- 24 ml). The number of dissected lymph nodes was 16.4 +/- 4.0. With
      respect to scrutiny of surgical specimens, the distal safety margin was adequate
      (mean: 2.4 cm; range: 1.2-5.6 cm), and the circumferential resection margins were
      free of tumor invasion (mean: 8.6 mm; range: 2-18 mm). A total of 74 patients
      completed the evaluation of urinary function. For these 74 patients, the median
      duration of training for the Foley catheter was 7 days (range: 4-64 days). The
      voiding function after removal of the Foley catheter were good in 53 (71.6%)
      patients, fair in 17 (23.0%), and poor in four (5.4%). Of the 17 patients with
      fair bladder function, eight were transient dysfunction and recovered thereafter.
      Thirty-two male and 28 female patients who were sexually active before the
      operation responded to the assessment of sexual function. In male patients, the
      ejaculation was good in 18 (56.3%) patients, fair (decrease in ejaculatory
      amounts) in six (18.7%), and poor (retrograde ejaculation, failure to ejaculate)
      in eight (25%). The potency was good in 20 (62.5%) patients, fair in five
      (15.6%), and poor in seven (21.9%). In female patients, the sexual function was
      good in 15 (53.6%) patients, fair in four (14.3%), and poor in nine (32.1%).
      Specific sexual problems in women included lubrication (46.6%, n = 13),
      dyspareunia (39.2%, n = 11), sexual arousal (28.6%, n = 8), and orgasm in (32.1%,
      n = 9). CONCLUSIONS: By the laparoscopic approach, total preservation of pelvic
      autonomic nerves without compromise of the radical extirpation of tumor is
      technically feasible in the vast majority of patients with lower rectal cancer
      who have undergone concurrent chemoradiation therapy, thus facilitating the
      retention of genitourinary function in a significant proportion of such patients.

PMID- 17235720
TI  - Clinical characteristics and outcomes in patients with advanced rectal cancer: a
      national prospective cohort study.
AB  - PURPOSE: At the time of diagnosis, approximately one third of patients with
      rectal cancer present with advanced disease. In this study we focus on a group of
      patients with primary advanced rectal cancer considered as not operable. We
      address various clinical aspects relevant for decision-making in a group of
      patients in need of palliative care. METHODS: Between January 1997 and December
      2001, 4831 consecutive patients with rectal cancer were prospectively registered
      in the Norwegian Rectal Cancer Registry. In this national population-based
      cohort, 386 patients (8 percent) without surgical interventions were identified.
      These patients comprise the study population. Clinical characteristics and
      survivals were addressed. RESULTS: Patients not surgically treated were
      significantly older compared with other treatment groups (median age, 80 years;
      interquartile range, 72-86 vs. median age, 71 years; interquartile range, 62-79
      years) (P<0.001). Median survival time was 4.5 (range, 3.5-5.4) months,
      regardless of age, gender, or hospital category. Patients who received
      radiotherapy had a significantly increased survival (P<0.001) compared with
      patients not treated with radiation, with a median survival time of 10.2 (range,
      7.3-12.1) months vs. 2.8 (range, 2.1-3.6) months, respectively. Use of
      chemotherapy was not associated with improved survival. In multivariate analysis,
      only stage of disease and radiotherapy were independent predictors of better
      survival. CONCLUSION: Higher age and comorbidity seem to influence choice of
      treatment in this subgroup of patients with advanced rectal cancer disease. In
      nonsurgically treated patients, radiotherapy was associated with an improved
      survival. Our prospective, population-based cohort study emphasizes the dismal
      prognosis of these patients, which also should challenge our efforts and clinical
      approaches in palliative care.

PMID- 17235721
TI  - The economic impact of laparoscopic inguinal hernia repair: results of a double
      blinded, prospective, randomized trial.
AB  - For this study, 66 patients with a preoperative diagnosis of unilateral primary
      inguinal hernia were randomized to undergo laparoscopic totally extra peritoneal
      (TEP), laparoscopic transabdominal (TAPP), or open inguinal hernia repair with
      polypropylene mesh (Lichtenstein type). Both the operative team caring for the
      patient postoperatively and the patient were blinded to the operative approach by
      placement of a large dressing covering the abdomen, which was not removed until
      postoperative day 3. The patients recorded their pain level on a visual analog
      pain scale daily. Medication usage also was recorded. All patients were seen at 7
      day intervals until they returned to work. The patients were interviewed during
      their postoperative visits by an investigator blinded to the operative approach
      and questioned regarding their ability to return to work and their pain levels.
      The average number of lost work days in all the groups was 12, and there was no
      significant difference between the three groups (p = 0.074). The average
      operating time for the TAPP procedure was 59 min, less than the time required to
      complete either the TEP or the Lichtenstein approach, which had equivalent
      operative times (p = 0.027). The material cost was significantly lower for the
      Lichtenstein repair (1,200 dollars less) than for either of the laparoscopic
      approaches, a saving primarily related to consumable operating room supplies. The
      TEP repair costs were minimally higher than those for the TAPP repair (125
      dollars more). No significant differences were noted in the postoperative pain
      scales, and the use of postoperative oral analgesics was equivalent. The higher
      operative costs noted for the laparoscopic hernia repairs were not offset by a
      shortened convalescence. Postoperative pain appears to be equivalent regardless
      of the operative approach chosen and is easily managed with oral analgesics.

PMID- 17235722
TI  - Validation of esophageal Doppler for noninvasive hemodynamic monitoring under
      pneumoperitoneum.
AB  - BACKGROUND: Commonly used perioperative measurements of hemodynamics, such as
      Swan-Ganz catheter assessment, are invasive and may not be reliable under
      pneumoperitoneum. The purpose of this study was to validate the use of esophageal
      Doppler for noninvasive hemodynamic monitoring under pneumoperitoneum in an
      experimental pig model. METHODS: Eight female pigs were submitted to two 30-min
      study periods, one each for the baseline (no interventions) and pneumoperitoneum
      (12-mmHg carbon dioxide pneumoperitoneum) conditions. One pig was excluded
      because of tachycardia (>140 at baseline). A Swan-Ganz pulmonary artery catheter
      was used to measure cardiac output (CO-SG) and pulmonary capillary wedge pressure
      (PCWP). An esophageal Doppler probe was inserted to record cardiac output (CO-ED)
      and corrected flow time (FTc), an index of preload. Transthoracic
      echocardiography was used to measure left ventricular end-diastolic diameter
      (LVEDD) and cardiac output (CO-TTE). Pearson correlation was used to assess
      individual associations between the measured hemodynamic parameters. RESULTS:
      There was good correlation between CO-ED and CO-SG (r = 0.577; p < 0.001) and
      excellent correlation between CO-ED and CO-TTE (r = 0.815; p < 0.001). There was
      no correlation between FTc and LVEDD or PCWP. These relationships were consistent
      when analyzed separately at baseline and during pneumoperitoneum. CONCLUSION:
      Esophageal Doppler monitoring is a valid noninvasive method of estimating cardiac
      output at baseline and during pneumoperitoneum in a porcine model. Corrected flow
      time did not correlate with other estimates of preload at baseline or during
      pneumoperitoneum.

PMID- 17235723
TI  - Transnasal small-caliber esophagogastroduodenoscopy for preoperative evaluation
      of the high-risk morbidly obese patient.
AB  - BACKGROUND: Esophagogastroduodenoscopy (EGD) is an important facet of the
      preoperative evaluation for bariatric surgery. Morbidly obese patients are at
      high risk for airway complications during this procedure, and an attractive
      alternative is transnasal EGD. This report describes a series of patients
      evaluated successfully using this technique. METHODS: All patients undergoing
      preoperative transnasal small-caliber EGD for morbid obesity surgery between
      September 2004 and June 2005 at a Veterans Affairs Hospital were included in the
      analysis. The variables assessed were the adequacy of the examination, patient
      tolerance, the need for sedation, and the ability to perform interventions.
      RESULTS: The study enrolled 25 patients (17 men and 8 women) with an average age
      of 55 years (range, 44-63 years) and an average body mass index (BMI) of 47 kg/m2
      (range, 38-69 kg/m2). All the patients met the 1991 National Institutes of Health
      (NIH) Consensus Conference Criteria for bariatric surgery and were undergoing
      preoperative evaluation. The most common comorbidities were hypertension (82%),
      diabetes mellitus (80%), and obstructive sleep apnea (68%). All 25 patients had
      successful cannulation of the duodenum's second portion with excellent tolerance.
      There were no sedation requirements for 23 (92%) of the 25 patients. Significant
      pathology was found in 14 (56%) of the 25 patients, including hiatal hernia
      (28%), gastritis (16%), esophageal intestinal metaplasia (16%), esophagitis
      (12%), gastric polyps (8%), gastric ulcer (4%) and esophageal varices (4%).
      Biopsies were indicated for 12 patients and successful for all 12 (100%).
      CONCLUSION: Transnasal small-caliber EGD is a feasible and safe alternative to
      conventional EGD for the preoperative evaluation of patients undergoing bariatric
      surgery. It requires minimal to no sedation in a population at high risk for
      complications in this setting. In addition, this technique is effective in
      identifying pathology that requires preoperative treatment and offers a complete
      examination with biopsy capabilities. This technique should be considered for all
      morbidly obese patients at high risk for airway compromise during EGD.

PMID- 17235724
TI  - Perception of airway obstruction and airway inflammation in asthma: a review.
AB  - Dyspnea has a multifactorial nature and the exact mechanism that causes
      breathlessness in asthma is not fully understood. There is compelling evidence
      that factors other than merely mechanical ones take part in the pathophysiology
      of breathlessness. Some recent reports attribute airway inflammation, which may
      contribute to the unexplained variability in the perception of dyspnea associated
      with bronchoconstriction. Eosinophil airway inflammation has been proposed as a
      determinant of breathlessness via mechanisms affecting either the mechanical
      pathways that control breathlessness or the afferent nerves involved in
      perception of dyspnea. In this review, data on the interrelation between
      inflammation and dyspnea sensation and the impact of treatment on dyspnea
      sensation are discussed. We conclude that regardless of whether mechanical or
      chemical inflammatory factors are involved, much variability in dyspnea scores
      remains unexplained.

PMID- 17235725
TI  - Release of soluble E-selectin from activated endothelial cells upon apoptosis.
AB  - Circulating soluble E-selectin is increased in diseases associated with
      endothelial apoptosis such as sepsis and acute respiratory distress syndrome. We
      investigated the mechanism by which endothelial cell (EC) apoptosis may promote
      soluble E-selectin release. We found that serum deprivation of EC caused
      apoptosis, yet it did not induce E-selectin EC surface expression. Tumor necrosis
      factor-alpha (TNFalpha) significantly increased EC E-selectin surface expression.
      Soluble E-selectin was noted, however, only in the medium of TNFalpha-activated,
      apoptotic EC. Preincubation of the EC with the caspase inhibitor z-VAD-fmk
      significantly attenuated soluble E-selectin levels in the culture medium of
      TNFalpha-activated, apoptotic EC, but it had no effect on E-selectin surface
      expression. These results indicate that TNFalpha activation, but not apoptosis,
      is necessary for E-selectin surface expression in EC. Furthermore, E-selectin
      release from EC requires caspase-3 activation. Thus, increased concentrations of
      circulating E-selectin in serum may serve as a marker for endothelial apoptosis
      in certain disease states.

PMID- 17235726
TI  - The role of c-erbB-2 expression on the survival of patients with small-cell lung
      cancer.
AB  - The aim of this study was to determine the incidence and role of c-erbB-2
      overexpression as a predictive/prognostic marker in small-cell lung carcinoma
      (SCLC). We performed a retrospective study on subjects with a biopsy-proven
      diagnosis of SCLC. A chart review for demographic and clinical data was performed
      on patients with SCLC diagnosed between 1998 and 2004. c-erbB-2 overexpression
      was evaluated using immunohistochemistry performed on archival paraffin-embedded
      specimens. Sixty-seven patients with SCLC were identified (6 females, 61 males;
      median age- 56.5 yr, range-34-75) all of whom had adequate tissue specimens
      available for c-erB-2 testing. Of the 67 specimens, 12 (17.9%) showed c-erbB-2
      overexpression. Seventy-five of the cases were positive for c-erbB-2, had
      extensive disease. The median overall survival of patients with SCLC whose tumors
      were positive and negative for c-erbB-2 were 8 +/- 0.9 months (95%CI 6.3-9.7) and
      11 +/- 1.5 months (95%CI 8.0-14.0), respectively. c-erbB-2 overexpression
      detected using immunohistochemistry is observed in 17.9% of patients with SCLC
      and has statistically significant prognostic value. Our findings suggest that c
      erbB-2 may be a potential target for site-specific immunotherapy in SCLC.
      Considering one technique examined, further molecular investigation is needed to
      confirm these preliminary findings.

PMID- 17235727
TI  - Clinical characteristics of a second small nodule(s) associated with cT1-2N0M0
      non-small-cell lung cancer.
AB  - When a patient with cT(1-2)N(0)M(0) stage non-small-cell lung cancer (NSCLC) has
      a second small nodule(s), the treatment plan and prognosis depend largely on
      whether the nodule is benign or malignant. However, the incidence of malignancy
      of nodules associated with N(0) and M(0) NSCLC is unknown. Furthermore,
      predictive factors of malignancy have not been defined. Thus, we evaluated the
      nature of nodules that were less than 15 mm in diameter associated with stage T(1
      2)N(0)M(0), and tried to identify clinical and radiologic factors predictive of
      malignancy. The study population consisted of 39 patients with T(1-2)N(0)M(0)
      NSCLC and a second nodule(s) less than 1.5 cm and who had received curative
      resection. Medical records and radiologic findings, including CT scans of the
      chest, were retrospectively reviewed. Nodules were finally diagnosed as benign in
      85% and malignant in 15%. No significant differences in terms of gender, age,
      preoperative carcinoembryonic antigen (CEA) level, cell type, pathologic stages,
      shape, size, location and number of nodules, or the presence of calcification
      around nodules was observed between benign and malignant groups. We suggest that
      if primary NSCLC is resectable, an effort should be made to confirm the
      pathologic diagnosis of nodules. If histologic findings in nodules are not
      available, surgical resection should be actively considered, especially when
      nodules < 1.5 cm are associated with N(0) or M(0) NSCLCs.

PMID- 17235728
TI  - Achieving full-dose, on-schedule administration of ACE chemotherapy every 14 days
      for the treatment of patients with extensive small-cell lung cancer.
AB  - Extensive small-cell lung cancer (SCLC) is commonly treated with multiple cycles
      of chemotherapy. Reducing the time interval between cycles of chemotherapy (dose
      dense chemotherapy) may improve outcomes in the treatment of extensive SCLC, as
      it has in other chemosensitive malignancies. To evaluate the feasibility of dose
      dense chemotherapy in patients with extensive SCLC, this study evaluates a dose
      dense doxorubicin/cyclophosphamide/etoposide (ACE) regimen, supported by the once
      per-cycle administration of the hematopoietic growth factor pegfilgrastim.
      Patients received up to six 14-day cycles of ACE chemotherapy (doxorubicin 40
      mg/m,(2) cyclophosphamide 1000 mg/m(2), etoposide 120 mg/m(2) on day 1 IV, plus
      oral etoposide 240 mg/m(2) daily on days 2-3). On day 4 of each cycle, patients
      received pegfilgrastim 6 mg by subcutaneous injection. Of 30 patients enrolled,
      27 started chemotherapy and received pegfilgrastim. Full-dose, on-schedule
      chemotherapy was given to all 22 patients starting cycle 2, and in 107 (88%) of
      121 cycles. Eighteen of the 27 patients (67%) received full-dose, on-schedule
      chemotherapy for all 6 cycles. The overall response rate was 17/27 (63%). Nine
      patients (33%) experienced hematologic toxicities that investigators considered
      severe or life-threatening. Four patients (15%) had febrile neutropenia. Full
      dose, on-schedule dose-dense ACE chemotherapy is feasible with once-per-cycle
      pegfilgrastim support in extensive SCLC.

PMID- 17235729
TI  - Green tea extract inhibits paraquat-induced pulmonary fibrosis by suppression of
      oxidative stress and endothelin-l expression.
AB  - Paraquat-induced pulmonary fibrosis involves two factors, direct injury by oxygen
      free radicals and indirect injury by inflammatory cells and fibroblasts.
      Endothelin-1 (ET-1) has been shown to act as a mediator of pulmonary fibrosis,
      and its formation increases during oxidative stress. We investigated whether
      green tea extract (GTE), which has antioxidant properties, inhibits paraquat
      induced pulmonary fibrosis and whether ET-1 is involved in this process. Paraquat
      (0.3 mg/kg) was instilled into the right lungs of rats, following which the rats
      were either not further treated (Group P, n = 7), or they were administered 1%
      GTE mixed with feed (Group PG; n = 7) or the ET(A) receptor antagonist ZD2574 (10
      mg/kg through gavage; Group PZ; n = 7) for two weeks. As control, we used rats
      instilled with saline (Group N; n = 6). Two weeks after paraquat instillation, we
      assayed the degree of pulmonary fibrosis by light microscopic morphometry and
      hydroxyproline content; lipid peroxidation as a marker of oxidative stresses by
      measurement of malondialdehyde (MDA); ET-1 by immunohistochemistry; and prepro-ET
      1 mRNA expression by reverse transcription-polymerase chain reaction. Compared
      with Group N, significant pulmonary fibrosis was observed in Group P, accompanied
      by increases in MDA, ET-1, and prepro-ET-1 mRNA expression. Compared with Group
      P, Group PG showed significant decreases in pulmonary fibrosis, along with
      decreases in MDA, ET-1, and prepro-ET-1 mRNA expression. We also observed
      significant decreases in pulmonary fibrosis in Group PZ compared with Group P.
      These findings suggest that GTE inhibits paraquat-induced pulmonary fibrosis by
      suppression of oxidative stress and ET-1 expression.

PMID- 17235730
TI  - Pulmonary hemosiderosis in association with celiac disease.
AB  - A 15-year-old male had a history of increasing dyspnea on exertion, cough, sputum
      production, fever, weakness, hemoptysis, and diarrhea. Chest radiography
      demonstrated bilateral alveolar consolidation. Bronchoalveolar lavage fluid
      analysis revealed extensive hemosiderin-laden alveolar macrophages. On the basis
      of iron deficiency anemia, diarrhea, raised antigliadin and antiendomysial
      antibodies, widespread villous atrophy, and crypt hyperplasia on intestinal
      biopsy, celiac disease was diagnosed. After treatment with a gluten-free diet,
      all his clinical symptoms and radiographic findings improved within two weeks.

PMID- 17235731
TI  - Squamous cell carcinoma of the lung: pattern of epidermal growth factor receptor
      mutation distribution in different populations: a summary.

PMID- 17235963
TI  - Cross-reactivity between pollen extracts from six artemisia species.
AB  - Pollen extracts of six different ARTEMISIA species, A. VULGARIS, A. SCOPARIA, A.
      PRINCEPS, A. TRIDENTATA, A. ANNUA, and A. CAMPESTRIS were compared using SDS
      PAGE, IEF, immunoblotting, and immunoelectrophoretic methods. The band patterns
      obtained after SDS-PAGE and IEF showed a large degree of similarity between the
      extracts. Immunoblotting of these gels using a pool of sera from patients
      allergic to A. VULGARIS gave essentially the same IgE-binding band pattern with
      all the extracts, demonstrating an extensive degree of cross-reactivity between
      A. VULGARIS and the other ARTEMISIA species. FRIE using a polyspecific antiserum
      against A. VULGARIS showed that all the extracts contained several antigens that
      were immunologically identical to antigens in A. VULGARIS extract. Antigens
      showing immunological identity to the important A. VULGARIS allergens Ag 12 and
      ART V II were present in all the extracts. The cross-reactivity between A.
      VULGARIS and A. PRINCEPS was further verified by screening of ten Korean and nine
      Norwegian individual patient sera against extracts of both species in SDS-PAGE or
      IEF immunoblotting. Both groups of patients had essentially the same pattern of
      reactivity towards both pollen extracts.

PMID- 17235964
TI  - Ontogenic Aspects of Ginkgolide Production in Ginkgo biloba.
AB  - The ontogenic aspects of ginkgolide production were studied by using GINKGO
      BILOBA seedlings, greenhouse plants, young trees, mature trees cuttings, and
      plant tissue cultures. Ginkgolide yield appeared to be increased with the age of
      the plants when the plants were grown under the same environmental conditions.
      Ginkgolide content in the leaves was increased when seedlings, young plants, and
      young trees were treated with fluridone, a carotenoid biosynthesis inhibitor.
      Ginkgolides appeared to be independently biosynthesized in leaves and roots of
      the GINKGO and stored in root bark and stem as more hydroxylated forms such as
      ginkgolide B or ginkgolide C.

PMID- 17235965
TI  - Inhibition of tyrosine activity by cultured lichen tissues and bionts.
AB  - Axenic, cultured thallus tissues from forty-six species of lichens were evaluated
      for their inhibitory effect on tyrosinase activity. Methanol extracts of tissues
      of three lichens, i.e. HYPOGYMNIA PHYSODES, LETHARIA VULPINA, and CETRARIA
      JUNIPERINA strongly inhibited tyrosinase activity, but extracts from the
      corresponding natural thalli showed only weak inhibition. The mycobiont of
      HYPOGYMNIA PHYSODES showed a higher inhibitory action than its photobiont.

PMID- 17235966
TI  - Bioactive Diterpenoids Isolated from Dilophus ligulatus.
AB  - Nine diterpenoids, acetyldictyolal ( 1), epoxyoxodolabelladiene ( 2),
      dictyotalide B ( 3), neodictyolactono ( 4), pachylactone ( 5), the acetals 6A and
      6B, isoacetoxycrenulatin ( 7), and dictyolactone ( 8) were isolated from the
      brown alga DILOPHUS LIGULATUS (Kutz.) Feldm. Their structures have been
      elucidated by comparison of mass, IR, (1)H- and (13)C-NMR spectra with reported
      literature data. Compounds 1, 2, 4, 7, and 8 exhibited antifungal activity.
      Cytotoxic activity against several types of mammalian cells (KB, P-388, P
      388/DOX, and NSCLCN6-L16) in culture was examined for the 8 diterpenoids. Some of
      them showed stronger cyto-toxicity than mercaptopurine which was used as a
      positive control in this study.

PMID- 17235967
TI  - 2-Methoxycanthin-6-one: A New Alkaloid from the Stem Wood of Quassia amara.
AB  - A new alkaloid, 2-methoxycanthin-6-one ( 1) has been isolated from the methanol
      extract of the stem wood of QUASSIA AMARA. In addition quassin ( 6) was also
      isolated. The structure of 1 was determined by spectroscopic methods.

PMID- 17235968
TI  - Two New Pavine Alkaloids from Thalictrum simplex.
AB  - Two new pavine alkaloids (-)-2-demethylthalimonine and (-)-9-demethylthalimonine
      together with the known argemonine have been isolated from the aerial parts of
      THALICTRUM SIMPLEX widespead in Mongolia. The structures have been elucidated on
      the basis of IR, EI-MS, and (1)H-NMR analyses as well as chemical transformation,
      respectively.

PMID- 17235969
TI  - Proanthocyanidins from Quercus petraea Bark.
AB  - Flavanols and oligomeric proantho-cyanidins were isolated from oak bark ( QUERCUS
      PETRAEA) and characterized by acid hydrolysis, gel permeation chromatography,
      haemanalysis, and complete as well as partial thiolytic degradation. The proantho
      cyanidins had an average polymerization degree of 6.1 and a procyanidin:
      prodelphinidin ratio of 6:4. The prevailing units of the oligomeric chains were
      (+)-catechin, (-)-epicatechin, and (+)-gallocatechin, minor units were (-)
      epicatechin 3- O-gallate and (-)-epigallocatechin 3- O-gallate. The bark contains
      both hydrolyzable and condensed tannins. Although only 23% of the water-soluble
      oak bark tannins consisted of oligomeric proanthocyanidins, these contributed
      with 55% to the astringency of the total tannin fraction.

PMID- 17235970
TI  - A beta-Hydroxychalcone from Leptospermum scoparium.
AB  - A beta-hydroxychalcone 1, so far not reported as a natural compound, was
      separated from the diethyl ether extract of LEPTOSPERMUM SCOPARIUM (Myrtaceae).
      Furthermore, three known flavonoids 2-4 were isolated. The (13)C-NMR spectra of 2
      4 are reported, since they have as yet not been reported in the literature.

PMID- 17235971
TI  - Cucurbitacins as Constituents of Wilbrandia ebracteata.
AB  - The methanolic extract from the roots of WILBRANDIA EBRACTEATA afforded, in
      addition to the known dihydrocucurbitacins B and E, dihydroisocucurbitacin B,
      Cucurbitacins B, D, E, G, H, P, and 22-deoxycucurbi-tacin D, four new compounds
      whose structures were elucidated as (20 R,24xi)-3)3beta,16alpha,20)24,25
      pentahydroxy-10alpha-cucurbit-5-ene-2,11,22-trione (3- EPI-isocucurbitacin G) (
      8), (20 R,22xi)-2beta16a,20,22,25-pentahydroxy-10alpha-cucurbita-5,23 T-diene
      3,11-dione ( 13), (20 R)-25-acetoxy-3,16alpha,20-trihydroxy-30- NOR-2-(beta- D
      glucopyranosyloxy)-1,2,3,4,5,10-dehydrocucurbit-6-ene-11,22-dione ( 14), and
      dihydroisocucurbitacin B-3-glucoside ( 16).

PMID- 17235972
TI  - Rofficerone: A New Triterpenoid from Rosmarinus officinalis.

PMID- 17235973
TI  - Alkaloids of Cocculus pendulus.

PMID- 17235975
TI  - Isolation and Structure Elucidation of p-Hydroxycinnamic Acid Esters from the
      Rhizome of Agropyron repens; Part I.

PMID- 17235974
TI  - Kauranoid Diterpenes in Gynoxys oleifolia.

PMID- 17235976
TI  - Constituents of the Essential Oil of Solidago canadensis ("Goldenrod") from
      Poland - A Correction.

PMID- 17235977
TI  - Constituents of the Essential Oil from the Flowers of Chromolaena odorata.

PMID- 17235978
TI  - Flavonol Glycosides from Heteropappus altaicus and H. biennis.

PMID- 17235979
TI  - Flavonoids from the Aboveground Parts of Eryngium campestre.

PMID- 17235980
TI  - Alkaloids from Ficus pachyrhachis.

PMID- 17235982
TI  - Flavonoids and Caffeic Acid Esters from Dichrocephala bicolor.

PMID- 17235981
TI  - Flavonoids and Ionone-Related Compounds from Oreocnide rubescens.

PMID- 17235983
TI  - (+)-Angustifoline: A Minor Alkaloid from Lupinus albus1.

PMID- 17235984
TI  - (R)-Magnocurarine from Evodia cf. trichotoma.

PMID- 17235986
TI  - Erratum.

PMID- 17235985
TI  - Reviews of three books on medicinal plants from India.

PMID- 17235987
TI  - Factors Affecting the Growth and Hyoscyamine Production during Batch Culture of
      Transformed Roots of Datura stramonium.
AB  - The growth and hyoscyamine production of transformed roots of DATURA STRAMONIUM
      (cell line DS 1) were investigated in batch culture experiments at three
      different temperatures and in media of varying total ion composition and sucrose
      level. Growth rate was not greatly affected by the level of Gamborg's B5 salts or
      the sucrose concentration. Growth rates of roots in a range of media were similar
      at 25 degrees C (doubling time T (d) 1.2-1.6 days) and at 30 degrees C (T (d) 1.2
      1.7 days) but roots grew slower at 20 degrees C (T (d) 1.9-3.5 days). The total
      root yield on a fresh weight basis was higher in full strength B5 media compared
      with half strength B5 media at all sucrose levels tested. However, the dry weight
      content of the roots increased significantly (4-20%) as the sucrose level in the
      medium was raised (2-10%) at each of the three temperatures. At 20 degrees C, the
      hyoscyamine content of the roots was higher than that at 25 degrees C or 30
      degrees C at all sucrose levels tested and was unaffected by increasing sucrose
      levels. However, increasing the level of sucrose (1-5%) in either half or full
      strength B5 media at 25 degrees C or 30 degrees C increased the hyoscyamine
      content of the roots by up to eight fold. At 20 degrees C, the total yield of
      hyoscyamine per flask or per unit of sucrose supplied was also higher than at 25
      degrees C or 30 degrees C with sucrose levels up to 5%. The highest rates of
      hyoscyamine production by cell line DS 1 were obtained with full strength B5
      medium with 5% sucrose at either 20 degrees C or 25 degrees C. Under these
      conditions, rates of hyoscyamine formation of up to 7.4 mg/l/d were observed
      under batch culture conditions. The amount of hyoscyamine released into the
      culture medium was much greater at 30 degrees C (up to 14% of the total) than at
      either 20 degrees C or 25 degrees C (up to 4% of the total).

PMID- 17235988
TI  - Embryoid Formation by High Temperature Treatment from Multiple Shoots of Panax
      ginseng1.
AB  - We developed a new technology to induce embryoids by a moderate high temperature
      treatment from multiple shoots of PANAX GINSENG (Araliaceae). The number of
      formed embryoids was 10 times higher than that of untreated tissue. Normal
      plantlets were regenerated from the embryoids by transplanting them on a hormone
      free medium. They contained ginsenosides Rb (1), Rg (1) and the other saponins as
      well as those of natural ginseng.

PMID- 17235989
TI  - Distribution Pattern of Saponins in Different Organs of Glycyrrhiza glabra.
AB  - Soyasaponins were detected by GC and GC-MS in different organs of GLYCYRRHIZA
      GLABRA, particularly in the seed, hypocotyl and rootlet, whereas glycyrrhizin was
      detected exclusively in the thickening root and the stolon. An inverse
      relationship was found between the soyasaponins content and the glycyrrhizin
      content in the growing stolon and in the roots at different stages of growth.

PMID- 17235990
TI  - New Phenolic Derivatives from Galeola faberi.
AB  - Seven phenolic derivatives, 2,4-bis(4-hydroxybenzyl)phenol ( 1), bis[4(beta- D
      glucopyranosyloxy)-benzyl] ( S)-(-)-2-isopropylmalate ( 2), bis[4-(beta- D-gluco
      pyranosyloxy)benzyl] ( S)-(-)-2-sec-butylmalate ( 3), 4-hydroxybenzyaldehyde (
      4), 4,4'-dihydroxydiphenyl-methane ( 5), 4-hydroxybenzyl alcohol ( 6), and 4
      (beta- D-glucopyranosyloxy)benzyl alcohol ( 7), were isolated from the rhizome of
      GALEOLA FABERI for the first time. Substance 1 is a new natural compound; 2 is
      identical with the previously isolated and characterised Substance V from GALEOLA
      SEPTENTRIOUS. It is accompanied in the plant here studied by the novel homologue
      3. Their structures were established by chemical and spectral methods.

PMID- 17235991
TI  - Nepehinal: A New Triterpenoidal Aldehyde from Nepeta hindostana.
AB  - A new triterpenoidal aldehyde, nepehinal ( 1), has been isolated from the
      alcoholic extract of the whole plant of NEPETA HINDOSTANA. Its structure was
      established as 1beta,3beta,1 1alpha-trihydroxy-lup-20(29)-en-30-al through
      chemical and spectroscopic studies including two dimensional NMR. (13)C-NMR
      spectral assignments of nepeticin ( 2) have also been revised.

PMID- 17235992
TI  - A New Oleanic Acid Derivative from Securinega tinctoria.
AB  - The triterpenoid constituents of the chloroform extract of previously defatted
      material of the stems of SECURINEGA TINCTORIA were examined and, besides beta
      sitosterol beta- D-glucopyranoside, a new oleanolic acid derivative was isolated
      and identified as 3beta( P-hydroxy- TRANS-cinnamoyloxy)olean-12-en-28-oicacid.

PMID- 17235993
TI  - A comparative study of commercial samples of ephedrae herba.
AB  - A total of 22 commercial Ephedra herba samples which belonged to EPHEDRA SINICA,
      E. INTERMEDIA, E. EQUISETINA, and E. DISTACHYA, respectively, were collected from
      the Taiwan herbal market. The contents of the six ephedrine alkaloids - ephedrine
      (E), pseudoephedrine (PE), methylephedrine (ME), methyl-pseudoephedrine (MPE),
      norephedrine (NE), and nor-pseudoephedrine (NPE) - in these samples were
      determined by capillary electrophoresis and were found to differ greatly among
      the samples. Generally, E. SINICA was superior (1.594 +/- 0.467%) and E.
      INTERMEDIA was inferior (1.210 +/- 0.372%). Among the individual constituents,
      the sum of E and PE contents in each sample was about nine-tenths of the total
      alkaloids, and the ratios of E/PE, ME/MPE, and NE/NPE in the given species were
      definite and could be used to aid in identifying the origin of the herbs. The
      alkaloid contents were found to be higher in the internodes of the herbs and in
      those items with thin stems, more powdery and less fibrous characters. There were
      no indications for alkaloids in the roots of the plants.

PMID- 17235994
TI  - Ontogenic aspects of ginkgo polyprenols.

PMID- 17235995
TI  - The Alkaloids of Psychotria rostrata.

PMID- 17235996
TI  - Constituents of Boenninghausenia albiflora: Isolation and Identification of Some
      Coumarins.

PMID- 17235997
TI  - Phenylpropanoid Glycosides from Avicennia marina.

PMID- 17235998
TI  - Uvariopsamine from the Stem Bark of Greenwayodendron oliveri1.

PMID- 17235999
TI  - 1alpha-Angeloyloxy-8beta,10beta-dihydroxyeremophil-7(ll)-8alpha,12-olide from
      Roldana sessilifolia1.

PMID- 17236000
TI  - Composition of the Essential Oil of Calamintha grandiflora.

PMID- 17236001
TI  - Antidiabetic Activity of Roots of Salacia macrosperma.
AB  - Various fractions of the alcoholic extract of the roots of SALACIA MACROSPERMA
      were evaluated for their antidiabetic activity in alloxan-diabetic rats by
      estimating various biochemical parameters in blood, viz. glucose, proteins,
      lipids, cholesterol, and free fatty acids, after oral administration for 8 days.
      From the data obtained, it is concluded that the methanolic fraction followed by
      the residual fraction of the alcoholic extract exhibited significant antidiabetic
      activity. These biofractions were able to correct the metabolic abberations in
      diabetic rats. This activity may be due to their insulin-like properties.

PMID- 17236002
TI  - Tropane alkaloid production in transformed root cultures of brugmansia Candida.
AB  - Transformed root cultures of BRUGMANSIA CANDIDA were established by infection
      with AGROBACTERIUM RHIZOGENES LBA 9402. Several clones with different growth
      index and tropane alkaloid pattern and content were obtained and two were
      examined in depth. The alkaloid content and pattern changed during the time
      course. At 21 days of culture clone 1 revealed an alkaloid spectrum dominated by
      3alpha-acetoxytropane (about 50% of the total alkaloid) and hyoscyamine (about
      25%), with a ratio of hyoscyamine to scopolamine of 11.2. In clone 40 this ratio
      was 1.5 and the content of 3alpha-acetoxytropane was low (2%). The maximum
      concentrations of hyoscyamine were obtained at 3 weeks of culture, and were 700
      and 500 microg/g FW in clone 1 and 40, respectively.

PMID- 17236003
TI  - Tropane Alkaloid Levels in the Leaves of Micropropagated Datura innoxia Plants.
AB  - Three androgenic DATURA INNOXIA Mill. (Solanaceae) plants which had been
      characterised in regard to their tropane alkaloid levels were micropropagated
      through axillary buds. The alkaloid contents in the leaves of more than 300
      micropropagated plants were investigated by ELISA and HPLC, after one and two
      culture cycles and compared to those of one of seedlings obtained from the same
      original line from which the androgenic plants had been produced. The plant with
      the higher alkaloid level yielded the population with the most alkaloids. After a
      second cycle of micropropagation, all the populations contained more alkaloids
      than those they had been derived from. All the micropropagated plant populations
      contained higher levels of alkaloids than plants grown from seeds.

PMID- 17236004
TI  - Purification and Characterization of a Flavone 7-O-Glucoside-Specific Glucosidase
      from Ligulate Florets of Chamomilla recutita.
AB  - Flavone content and glucosidase activity were analyzed in various species of the
      genera Chamomilla, Matricaria, and Anthemis, especially during the development of
      the chamomile flower heads. The accumulation profile of flavonoids and the
      increase in enzyme activity were similar during ontogenesis. The accumulation of
      apigenin derivatives in closely related species was always linked to the
      occurrence of a catabolic beta-glucosidase in the respective plant organ. The
      flavone-glucoside-cleaving beta-glucosidase (FGG) from the ligulate florets of
      chamomile was purified to electrophoretic homogeneity by the following procedure:
      ammonium sulphate fractionation, anion exchange on Mono Q, hydrophobic
      interaction chromatography on Bio-Gel TSK Phenyl-5-PW, and gel filtration on
      Superose 12. The M (r) of the native enzyme was determined by gel filtration (500
      kDa) and native PAGE (334 kDa). Only one subunit with an M (r) of 60 kDa could be
      detected after SDS-PAGE. The isoelectric point as determined by chromatofocussing
      on Mono P was at pH 4.6. During the purification procedure only one glucosidase
      activity appeared. A partially purified enzyme was used for characterization. The
      temperature optimum was at 37 degrees C and the pH-optimum 5.6. Energy of
      activation was 32.9 kJ/mol. The determination of the kinetic constants with
      various aryl glycosides proved a high affinity of the FGG towards flavone 7- O
      glucosides. alpha-Glycosides and disaccharides were not hydrolyzed.
      Transglucosylation to an acceptor other than water was observed. Reagents
      interacting with sulfhydryl-groups strongly inhibited the enzyme.

PMID- 17236005
TI  - Enzyme immunoassay for the quantitative determination of galanthamine.
AB  - An enzyme immunoassay for the quantitation of fmol amounts of the therapeutically
      important Amaryllidaceae alkaloid, galanthamine, was established. The antiserum
      was raised against a conjugate of galanthamine-2- O-hemisuccinate-bovine serum
      albumin. The antibodies used were isolated and purified by Rivanol treatment with
      subsequent (NH (4)) (2)SO (4) precipitation. The measuring range of the assay
      extends from 2 to lOO pg of galanthamine, and as little as 3.5 fmol may be
      detected. The antibodies are highly specific for galanthamine, showing no cross
      reactivity with several Amaryllidaceae alkaloids. This assay allows the rapid,
      sensitive and precise quantitation of galanthamine in unpurified plant extracts
      as well as biological fluids. The galanthamine content in a variety of herbarium
      material as well as the frequency distribution of galanthamine in 1000 LEUCOJUM
      AESTIVUM plants from various origins in South Bulgaria have been investigated.
      The preliminary results demonstrate that the galanthamine-specific enzyme
      immunoassay can be a useful tool in medicinal plant breeding, for screening
      programs, as well as for taxonomic and pharmacokinetic studies.

PMID- 17236006
TI  - Characterization of Three Labdane Diterpenes from Aframomum alboviolaceum.
AB  - Two labdane diterpenes were isolated from the seeds and the rhizomes of AFRAMOMUM
      ALBOVIOLACEUM (Ridley) K. Schum (Zingiberaceae) and identified by GC-MS, (1)H-,
      and (13)C-NMR as ( E)-labda-8(17),12-diene-15,16-dial ( 1) and ( E)beta,17-epoxy
      labd-12-ene-15,16-dial ( 2). A third minor compound could be the methyl ( E)
      14xi,15-epoxylabd-8(17),12-dien-16-oate. The simultaneous occurrence of these
      three molecules has been mentioned only in one other species of the same genus,
      AFRAMOMUM DANIELLII (1).

PMID- 17236007
TI  - A New Triterpenoidal from Vernonia cinerea.
AB  - From the roots of VERNONIA CINEREA Less. (Compositae) a new triterpenoid has been
      isolated and characterised as 3beta-acetoxyurs-19-ene ( 1). A further constituent
      has been identified as lupeol acetate. Structure elucidation has been made with
      the help of spectral analyses.

PMID- 17236008
TI  - A New Bidesmosidic Triterpenoidal Saponin from the Roots of Symphytum officinale.
AB  - A new triterpenoidal saponin having hederagenin as the aglycone was isolated from
      the roots of SYMPHYTUM OFFICINALE L. The structure of this saponin was elucidated
      by FAB-MS, (1)H-, (13)C-NMR, 2D-NMR analyses and chemical studies as 3- O-[beta-
      D-glucopyranosyl-(1-->4)-alpha- L-arabinopyranosyl]-hederagenin 28- O-[beta- D
      glucopyranosyl-(1-->6)-beta- D-glucopyranosyl] ester.

PMID- 17236009
TI  - Echinodol: A New Cembrene Derivative from Echinodorus grandiflorus.
AB  - The aerial parts of ECHINODORUS GRANDIFLORUS Mitch., a species of Alismataceae
      from Brazil, yielded a new diterpene alcohol named echiriodol ( 1) in addition to
      the known steroid stigmasterol. Its constitution and relative configuration were
      established by high resolution NMR techniques.

PMID- 17236010
TI  - Revised Stereochemistry of So-Called Isoselagine and Spectroscopic Analysis of
      6alpha-Hydroxylycopodine from Lycopodium serratum var. longipetiolatum.
AB  - The structure of isoselagine, isolated from the Chinese medicinal plant
      LYCOPODIUM SERRATUM Thunb. var. longipetiolatum Spring, was shown to be identical
      with huperzine A ( 1) and to have an exocyclic double bond in the E 
      configuration from NOE data. In the process of extraction of isoselagine, we also
      isolated and identified another alkaloid, 6alpha-hydroxylycopodine (L. 20) ( 2)
      that was found to occur in this plant for the first time. The structure of L. 20
      was previously determined mainly by the chemical means, and this is the first
      report on the analysis of its structure by (1)H- and (13)C-NMR with more advanced
      2D-NMR techniques. The X-ray crystallography revealed the stereochemistry of 2
      and confirmed its structure. The hemostatic properties of the isolated alkaloids
      were studied, but they showed no platelet aggregation activity.

PMID- 17236011
TI  - 5'- O -Demethylnarcotine: A New Alkaloid from Papaver somniferum.

PMID- 17236012
TI  - Valtrates and Lignans in Valeriana microphylla.

PMID- 17236013
TI  - New Acetophenone and Thymol Derivatives from Eupatorium stoechadosmum.

PMID- 17236014
TI  - Solamargine: The Main Glycoalkaloid from the Fruits of Solanum paludosum.

PMID- 17236016
TI  - List of referees 1993.

PMID- 17236015
TI  - Additional Terpenoids from Chrysactina mexicana1.

PMID- 17236017
TI  - About the bufadienolide complex of "red" squill.
AB  - Red coloured bulbs of plants of the URGINEA MARITIMA aggregate from the northern
      and southern Mediterranean area were shown to exhibit different bufadienolide
      compositions. Therefore, the bufadienolide complex of "red squill" samples from
      Tunesia and from Sardegna was investigated. Twelve bufadienolides were isolated
      from bulbs of tetraploid squill from Tunesia, sixteen from tetraploid samples
      from Sardegna. The Compounds were identified by means of FAB-MS, (1)H-NMR, and
      (13)C-NMR studies or comparison with authentic substances. Both of the samples
      contained scilliroside ( 14), scillarenin 3- O-beta- D-glucoside ( 2),
      proscillaridin A (1), scilliphaeosidin 3- O-beta- D-glucoside ( 5),
      scilliglaucoside ( 17), scilliphaeoside ( 4), and 12- EPI-scilliphaeoside ( 7);
      the bulbs from Tunesia contained additionally glucoscilliphaeoside ( 6) and the
      four new bufadienolides 12- EPI-glucoscilliphaeoside ( 10), 12beta
      hydroxyscilliglaucosidin 3- O-beta- D-glucoside ( 21), 12- EPI-scilliphaeosidin 3
      O-beta- D-glucoside ( 8), and 12- EPI-scilliphaeosidin 3- O-alpha- L-rhamnosido
      alpha- L-rhamnoside ( 9). In the bulbs from Sardegna scularen A ( 3),
      gamabufotalin 3- O-alpha- L-rhamnoside ( 20), scilliglaucoside ( 17),
      scillirubrosidin 3- O-alpha- L-rhamnoside ( 11), scillirubroside ( 12), 12beta
      hydroxyscilliroside ( 15), 5alpha-4,5-dihydroscillirosidin 3- O-alpha- L
      thevetosido-beta- D-glucoside ( 19), and deacetyl-scilliroside ( 8) besides the
      new Compounds 10-carb-oxy-5beta,14beta-dihydroxybufa-3,20,22-trienolide 5- O-beta
      D-glucoside ( 18) and scilliglaucogenin ( 16) were found in addition. Not only
      quantitative but even qualitative differences in the bufadienolide pattern
      between the samples of the northern and the southern Mediterranean area were
      proved. By now it is not clear whether the investigated samples belong to
      different chemodemes of URGINEA NUMIDICA or are two different species of the
      URGINEA MARITIMA aggregate.

PMID- 17236018
TI  - Salvianolic Acid I: A New Depside from Salvia cavaleriei.
AB  - A new depside named salvianolic acid I was isolated from the aqueous extract of
      SALVIA CAVALERIEI, along with salvianolic acids A, B, C, H, isosalvianolic acid
      C, lithospermic acid, and rosmarinic acid. The chemical struktures were
      determined by spectral analysis. Two methylated caffeic acid dimers were
      synthesized using ferulic acid as the starting material.

PMID- 17236019
TI  - Analysis of Hydrosoluble Polysaccharides from Ramonda myconi Leaves.
AB  - The mucilage of RAMONDA MYCONI leaves is composed of several Polysaccharides
      differing in acidity due to the content of galacturonic acid. RMP-2 and RMP-4 are
      the most important fractions, where RMP-2 is an arabinogalactan containing
      galacturonic acid and rhamnose, probably connected to a protein moiety. RMP-4 is
      the major fraction, containing a Polysaccharide with 90% of galacturonic acid. It
      has a pectin-like structure and the neutral sugar enriched regions show a
      structure related to the rhamnogalacturonan II type.

PMID- 17236020
TI  - Prostaglandin F2alpha and gamma-Linolenic Acid in Oenothera stricta.

PMID- 17236021
TI  - Novel Sesquiterpenes from Ligularia veitchiana.

PMID- 17236022
TI  - Sesquiterpene Lactones in Tissue Culture of Lactuca virosa.

PMID- 17236023
TI  - Alkaloids from Narcissus primigenius.

PMID- 17236024
TI  - Triterpene Acids from Cowainea mexicana.

PMID- 17236025
TI  - Constituents of the Hexane Extract from Dichrostachys glomerata.

PMID- 17236026
TI  - Phenolic Compounds from Santolina pinnata.

PMID- 17236027
TI  - Chemical and Biological Study of Astianthus viminalis.

PMID- 17236028
TI  - Pharmacological Screening of Plants Recommended by Folk Medicine as Snake Venom
      Antidotes; IV. Protection against Jararaca Venom by Isolated Constituents1.
AB  - Fifteen Compounds, isolated from plants reputed as snake venom antidotes,
      belonging to different classes of natural products, were shown to protect mice to
      a significant degree against the lethal action of the venom of BOTHROPS JARARACA
      snakes. Administration was by the oral route, one hour prior to envenomation. The
      substances are nitrogen-free, low-molecular-weight compounds for which some kind
      of biodynamic activity has previously been reported. The fact that they are
      mostly trivial, naturally-occurring compounds should explain why plants used as
      snake-bite antidotes are so widely distributed over the plant kingdom.

PMID- 17236029
TI  - Rutin and Scopoletin Content and Micropropagation of Fabiana imbricata.
AB  - An HPLC method for the simultaneous quantitative determination of rutin and
      scopoletin in the aerial parts of FABIANA IMBRICATA is presented. The results
      showed high variability in the scopoletin (240-2,400 mg%) and rutin (195-1,950
      mg%) content in the populations surveyed. A micropropagation method for F.
      IMBRICATA plants was established by culturing shoot tips on Murashige-Skoog (MS)
      medium containing 1.0 mg/l benzylaminopurine (BAP), 0.01 mg/l naphthaleneacetic
      acid (NAA), and 0.1 mg/l gibberellic acid (GA3). Auxin addition to the rooting
      medium, especially 0.5 mg/l indolebutyric acid (IBA) or 0.5 mg/l IBA and 0.1 mg/l
      NAA, enhances root formation. The micropropagation method presented allowed the
      obtention of regenerated plantlets in six weeks from shoot tips.

PMID- 17236030
TI  - Acridone Alkaloids from Cell Suspension Cultures of Thamnosma montana.
AB  - Cell Suspension cultures of THAMNOSMA MONTANA were grown in Gamborg B5 medium
      which was best suited for acridone alkaloid formation. From the lyophilized cell
      material nine acridones and three acridone-monoglucosides have been isolated
      which were found for the first time in the genus THAMNOSMA. Moreover, N
      methylacridone which is known from the intact plant was found. Gravacridonol
      monoglucoside was identified as a new alkaloid. Interestingly, most isolated
      alkaloids belong to the dihydrofuroacridones.

PMID- 17236031
TI  - Mass Production of Ginseng (Panax ginseng) Embryoids on Media Containing High
      Concentrations of Sugar1.
AB  - A lot of ginseng embryoids were produced by culturing on high concentrations of
      sugar media from the embryogenic tissues obtained by moderately high temperature
      treatment. When the sucrose concentration was 100 g/l, the number of embryoids
      produced were over 100 pieces per g of inoculum weight. It was about ten times of
      that produced by culturing on 30 g/l of sucrose. Glucose showed an effect similar
      to sucrose on the basis of weight percentage. However, mannitol did not show this
      effect. The embryoids obtained by these processes redifferentiated to normal
      plantlets on culturing on the medium containing 30 g/l of sucrose. The saponin
      components of the tissue containing embryoids showed a similar pattern to those
      of natural GINSENG by HPLC.

PMID- 17236032
TI  - Long-Term Effect of a Pythium Elicitor Treatment on the Growth and Alkaloid
      Production of Catharanthus roseus Cell Suspensions.
AB  - The treatment of a CATHARANTHUS ROSEUS cell suspension culture with a low
      concentration of PYTHIUM elicitor stimulated the alkaloid production. When these
      pretreated cells were resuspended in a medium that did not contain the fungal
      extract, the positive effects of the treatment on alkaloid synthesis and
      excretion were lost and, moreover, the standard level of production was not
      recovered. A second treatment of these cells with PYTHIUM elicitor at day 5 of
      the second culture cycle greatly impaired growth kinetics, but did not stimulate
      the alkaloid production observed with standard cultures. Repeated treatments with
      a low concentration of fungal elicitor seemed to have a negative long-term effect
      on both growth and alkaloid synthesis and did not appear to be a useful process
      for production purposes.

PMID- 17236033
TI  - Tropane Alkaloids in Transformed Roots of Datura quercifolia.
AB  - Hairy root cultures of DATURA QUERCIFOLIA were established following infection
      with AGROBACTERIUM RHIZOGENES strain LBA 9402. Eight tropane alkaloids were
      identified in the hairy roots, hyoscyamine being the major constituent. The
      growth and the hyoscyamine content of transformed roots were investigated under
      various conditions. Gamborg B5, Murashige and Skoog, and Woody Plant media were
      tested. Gamborg B5 medium was the best for growth as well as for hyoscyamine
      accumulation. The influence of sucrose concentration was examined and a 5%
      concentration was found to be the most appropriate for growth and for alkaloid
      production. After 35 days of incubation in this medium, the hyoscyamine content
      of the roots was 1.24% based on dry weight. The influence of gibberellic acid and
      of Amberlite XAD-4 resin on hyoscyamine production was tested.

PMID- 17236034
TI  - Phenolic Constituents of Selaginella doederleinii.
AB  - Eleven phenolic Compounds have been isolated from the ethanolic extract of
      SELAGINELLA DOEDERLEINII by a combination of Chromatographic techniques. These
      are five lignans: (-)-lirioresinol A, (-)-lirioresinol B, (+)-wikstromol, (-)
      nortracheloside, (+)-matairesinol ( 1), two phenylpropanones: 3-hydroxy-1-(3
      methoxy-4-hydroxyphenyl)-propan-1-one ( 2), 3-hydroxy-1-(3,5 -dimethoxy-4
      hydroxyphenyl)-propan-1-one ( 3), and four biflavonoids: amentoflavone, 7,7''-di-
      O-methylamentoflavone, 7,4',7'',4'''-tetra- O-methylamentoflavone, and
      heveaflavone ( 4). Compounds 1, 2, and 3 are novel natural secondary metabolites.
      Their structures were deduced from their spectral data (mainly (1)H-NMR, mass,
      and CD). Lignans are described here for the first time in the family
      Selaginellaceae. Their cytotoxic activity against L 929 murine cells accounts for
      the use of the plant in traditional Chinese medicine as an anticancer agent.

PMID- 17236035
TI  - Erythrina alkaloids: isolation and characterisation of alkaloids from seven
      erythrina species.
AB  - The alkaloids present in the seeds of seven ERYTHRINA species, E. FUSCA Lour, E.
      COSTARICENCIS M. Micheli, E. LEPTORHIZA A. DC., E. SPECIOSA Andrews, E. VARIEGATA
      L., E.MELANACANTHA Taubert ex Harms, and E. BERTEROANA Urban, have been screened
      by gas chromatography-mass spectrometry (GC/MS). The novel alkaloid erythrartine
      N-oxide has been isolated from E. BERTEROANA and characterized as an N-oxide of
      theknown alkaloid, erythrartine.

PMID- 17236036
TI  - Erysenegalenseins H and I: Two New Isoflavones from Erythrina senegalensis1.
AB  - In addition to the known Compounds senegalensin, lupinifolin, erythrisenegalone,
      and auriculatin, two new isoflavones named erysenegalensein H and
      erysenegalensein I were isolated from the dichloromethane extract of the stem
      bark of ERYTHRINA SENEGALENSIS DC. On the basis of spectroscopic methods their
      structures were elucidated as 5,2',4'-trihydroxy-8-(gamma,gamma-dimethylallyl)
      2''-hydroxyisopropyldihydrofurano[4'',5'':6,7]-isoflavone and 5,2',4'-trihydroxy
      8-(gamma,gamma-dimethylallyl)-3''-hydroxy-2'',2''-dimethyldihydropyrano
      [5'',6'':6,7]-isoflavone, respectively.

PMID- 17236037
TI  - Abietane Diterpenes from Tripterygium wilfordii.

PMID- 17236038
TI  - Application of High Speed Counter-Current Chromatography to the Separation of
      Stilbene Derivatives from the Roots of Lindera reflexa.

PMID- 17236039
TI  - C-Glycosoylflavones from Aerial Parts of Mimosa pudica.

PMID- 17236040
TI  - (trans-Pinocarveyl Hydroperoxide from Achillea ptarmica).

PMID- 17236041
TI  - Constituents from Piper divaricatum.

PMID- 17236042
TI  - Triterpenoids from Artocarpus integrifolia Fruits.

PMID- 17236043
TI  - Lipopolysaccharide-independent limulus amebocyte lysate activating, mitogenic and
      anti-complementary activities of pectic polysaccharides from chinese herbs.
AB  - Bioactive pectic polysaccharides from Chinese herbs were tested for the presence
      of lipopolysaccharide (LPS) or LPS-like substances by chromogenic Limulus
      amebocyte lysate (LAL)-assay. Pectic polysaccharides from BUPLEURUM FALCATUM,
      GLYCYRRIZA URALENSIS, and ANGELICA ACUTILOBA were LAL-positive at different
      rates. The fractions GR-2IIc/PG-1 (ramified region; rhamnogalacturonan core with
      neutral sugar side chains) from G. URALENSIS and AGIIb-1 (acidic arabinogalactan)
      from A. ACUTILOBA activated the endotoxin-mediated coagulation factor (factor C).
      When the pectin-like polysaccharide bupleuran 2IIc from B. FALCATUM was digested
      with ENDO-polygalacturonase or degraded with lithium, the resulting
      oligosaccharides still showed LAL-reactivity. Carboxyl-reduction of acidic
      polysaccharides increased the reactivity to the beta(1-->3)-glucan-mediated
      coagulation factor (factor G) but not the factor C. Bupleuran 2IIc and its PG-1
      and PG-2 (rhamnogalacturonan II-like region, which contains 2-keto-3
      deoxyocuturosonic acid) showed significant mitogenic activities even by using
      C3H/HeJ mice which are low responder mice to LPS. When the LAL-positive substance
      was removed from bupleuran 2IIc and its fraction PG-1 by phase separation using
      Triton X-114, the mitogenic and anti-complementary activities did not change.
      These results indicated that mitogenic and anti-complementary activity of
      bioactive pectic polysaccharides from B. FALCATUM were due to the action of
      pectic polysaccharides but not LPS.

PMID- 17236044
TI  - Content of thiophenes in transformed root cultures of argentinian species of
      tagetes.
AB  - The presence of thiophenes in four Argentinian species of TAGETES was studied. T.
      TERNIFLORA HBK and T. MINUTA L. seedlings contain 5-(4-hydroxy-1-butynyl)-2-2'
      bithienyl (BBTOH); 5-(4-acetoxy-1-butynyl)-2,2'-bithienyl (BBTOAc), while T.
      CAMPANULATA Griseb and T. LAXA Cabrera seedlings also accumulated BBT and alpha
      T. From the four TAGETES species tested only T. LAXA was able to produce
      transformed roots when infected with AGROBACTERIUM RHIZOGENES LBA 9402. Several
      clones of transformed roots were obtained in which the total thiophene content
      present showed considerable variations (277 to 1773 microg/g FW). The thiophene
      spectrum, however, was similar between different clones. In addition, the
      thiophene patterns in these transformed clones differed from that formed in the
      parent plants.

PMID- 17236045
TI  - New Sesquiterpene Lactones from Montanoa tomentosa subsp. xanthiifolia*.
AB  - A chemical examination of MONTANOA TOMENTOSA subsp. XANTHIIFOLIA afforded in
      addition to some known compounds, four new sesquiterpene lactones: 4beta,5alpha
      epoxy-8alpha-isobutyryloxy- TRANS-germacr-1(10)-en-12,6beta-olide ( 1A),
      4beta,5alpha-epoxy-7alpha-hydroxy-8alpha-isobutyryloxy- TRANS-germacr-1(10)-en
      12,6beta-olide ( 1B), (1 R,4 S)-1,5-cyclo-5alpha-hydroxy-8alpha-isobutyryloxy
      7alpha, 10alpha-oxagermacran-12,6beta-olide ( 2A), and 4beta-hydroxy-8alpha
      isobutyryloxy-7alpha,10alpha-oxaguaian-12,6beta-olide ( 3). The structures were
      determined mainly by spectroscopic methods. The structure of 1B was confirmed by
      an X-ray analysis.

PMID- 17236046
TI  - Constituents of the Egyptian Centaurea scoparia; Chlorinated Guaianolides of the
      Aerial Parts.
AB  - A new chlorine-containing guaianolide, chloroscoparin, was isolated from the
      ethanol extract of the aerial parts of CENTAUREA SCOPARIA Sieb. together with
      three known chlorine-containing guaianolides. The structures of the isolated
      compounds were elucidated by spectroscopic methods including (1)H-NMR-, 2D (1)H-
      (1)H COSY-, (13)C-NMR-, APT-, DEPT-, HETCOR-, long-range-HETCOR-, 2D INADEQUATE-,
      and mass spectra. The relative configuration was determined by 2D-NOESY studies.
      New NMR data for the known compounds are reported.

PMID- 17236047
TI  - Artemisinin, Related Sesquiterpenes, and Essential Oil in Artemisia annua During
      a Vegetation Period in Vietnam.
AB  - The active principle of ARTEMISIA ANNUA L., artemisinin, is currently being
      developed to a registered antimalarial drug. For production purposes, plants with
      a high artemisinin content are required. We followed the development of the
      artemisinin content and of the biosynthetically related sesquiterpenes
      artemisinic acid, arteannuin B, and artemisitene in A. ANNUA plants, during a
      vegetation period in Vietnam, where this species is indigenous. In addition, the
      essential oil content and composition were studied. Samples of leaves, buds,
      flowers, or post-bloom flowers and fruits were taken at different stages:
      vegetative (5, 6, and 8 months old), at mass formation of buds (9 months), at
      full bloom (10 months), and post-bloom (10S months). The highest artemisinin
      content (0.86% dry wt) was present in the leaves of 5 months-old plants. At this
      stage also the highest leaf yield was found. Subsequently, the artemisinin
      content gradually dropped. At the age of 5 months the highest artemisinic acid
      and arteannuin B contents, 0.16 and 0.08% dry wt, respectively, were found as
      well. Artemisitene was present at all stages of development, ranging from 0.002
      to 0.09% dry wt. With 1.9% v/w, the essential oil content was maximal just before
      flowering and was composed of 55% monoterpenes and 45% sesquiterpenes. At all
      other stages (0.4 - 1.0% v/w oil) this ratio was ca. 30%/70%. The main components
      of the oil were camphor and germacrene-D.

PMID- 17236048
TI  - Inhibitory effects of eugenol and related compounds on lipid peroxidation induced
      by reactive oxygen.

PMID- 17236049
TI  - Aconitine in Nectaries and Other Organs from an Icelandic Population of Aconitum
      napellus ssp. vulgare.

PMID- 17236050
TI  - Glucuronide Saponins of Oleanolic Acid from Achyranthes fauriei Roots.

PMID- 17236051
TI  - Acetylated Aurone Glucosides from Microglossa pyrifolia1.

PMID- 17236052
TI  - Quaternary Alkaloids of Papaver spicatum.

PMID- 17236053
TI  - 3alpha,5alpha-Tetrahydrodeoxycordifoline from Guettarda ovalifolia.

PMID- 17236054
TI  - Chemotypes of Murraya koenigii Growing in Sri Lanka1.

PMID- 17236055
TI  - On the Isolation and Characterization of a C-S-Lyase Preparation from Leek,Allium
      porrum.
AB  - The C-S-lyase protein from leek, ALLIUM PORRUM L., has been purified and
      characterized. The molecular mass of the native protein was determined with M (r)
      = 100 000, including two similar subunits, M (r) = 50 000. The tendency of the
      native protein to form a trimer, M (r) = 300 000, could be supported. The
      isoelectric point of the enzyme turned out to be close to pH 7.5. The C-S-lyase
      reaction revealed a wide pH optimum, in the range of 6.1 to 6.9. The temperature
      optimum was found to be at 41 degrees C. Pure (+)- and (-)-isomers of S-alk(en)yl
      L-cysteine sulfoxides were inserted as the substrates. The highest turnover rate
      was achieved with (+)- S-allyl- L-cysteine sulfoxide (alliin). (+)- S-Propyl- L
      cysteine sulfoxide (PCSO) exhibited the lowest K (m) value. Activation energies
      for the cleavage of the substrates were determined to be 23 kJ/mol for (+)- S
      methyl- L-cysteine sulfoxide (MCSO), 38 kJ/mol for (-)-MCSO, 28 kJ/mol for (+)
      alliin, and 54 kJ/mol for (+)-PCSO. On the basis of studies with specific
      inhibitors, pyridoxal 5'-phosphate was found to be part of the A. PORRUM C-S
      lyase protein as a cofactor. Competitive inhibitory effects were observed with L
      cysteine and related compounds.

PMID- 17236056
TI  - Purification and Characterization of a C-S-Lyase from Ramson, the Wild
      Garlic,Allium ursinum.
AB  - A C-S-lyase preparation from ramson, ALLIUM URSINUM L., has been purified to
      apparent homogeneity. Separation techniques applied were hydrophobic interaction
      chromatography, anion exchange chromatography, and gel permeation chromatography.
      A 52-fold purification was obtained. The enzyme could be characterized by a
      molecular mass of M (r) = 150000 with subunits of 50 000. Its isoelectric point
      was determined to be at 4.7. The pH-optimum for the substrate-dependent turnover
      was found at 6.0. The temperature optimum was at 35 degrees C. (+)-Alliin as the
      substrate caused the highest enzymatic reaction velocity. The lowest K (m) value
      was observed with (+)- S-propyl- L-cysteine sulfoxide. Inhibitor constants were
      elaborated for the deoxy-derivatives of the substrates inserted and, likewise,
      for related amino acids. The protein was sensitive to low concentrations of
      hydroxylamine, indicating pyridoxal phosphate as a cofactor. Activation energies
      were determined for the cleavage of alliin, S-propyl- L-cysteine sulfoxide and S
      methyl- L-cysteine sulfoxide, and were found to be in the range of 9 to 13 kJ .
      mol (-1).

PMID- 17236057
TI  - MEKC as an Improved Method to Detect Falsifications in the Flowers of Arnica
      montana and A. chamissonis.
AB  - ARNICA MONTANA and ARNICA CHAMISSONIS ssp. FOLIOSA flowers are often adultered by
      blending them with those from HETEROTHECA INULOIDES. TLC, HPLC, and TSP LC/MS
      have been proposed to detect this kind of falsification. A new method based on
      micellar electrokinetic chromatography (MEKC) has been developed. This procedure
      permits us to characterize rapidly each drug and to detect easily falsifications
      from H. INULOIDES in ARNICA drugs.

PMID- 17236058
TI  - Production of (-)-7-Hydroxyisopiperitenone from (-)-Isopiperitenone by a
      Suspension Cell Culture of Mentha piperita.

PMID- 17236059
TI  - Constituents of the Essential Oils from Piper sylvestre Growing in Mauritius.

PMID- 17236060
TI  - Separation of Alkaloids in Chelidonium majus by Reversed Phase HPLC.

PMID- 17236061
TI  - Spectrum of Tropane Alkaloids in Transformed Roots of Datura innoxia and
      Hyoscyamus x gyorffyi cultivated in Vitro.

PMID- 17236062
TI  - Ellagitannins from Alchemilla xanthochlora and Potentilla erecta*.

PMID- 17236064
TI  - Pentacyclic Triterpenes from Cnidoscolus multilobus1.

PMID- 17236065
TI  - Coumarins and Sesquiterpene Lactones from Magnolia grandiflora Leaves.

PMID- 17236063
TI  - Furoquinoline Alkaloids from Vepris heterophylla.

PMID- 17236066
TI  - Novel Galloylhamameloses from Hamamelis virginiana1.
AB  - The range of natural galloylhamameloses is extended by the recognition of the
      highly unstable novel analogues, the 1- O-(4-hydroxybenzoyl)-2',5-di- O-galloyl
      alpha- D-hamamelofuranose and its 1- O-beta-anomer. The observed facile
      elimination of the C-1 acyl moiety is discussed and a mechanism proposed. These
      compounds are accompanied in the bark of HAMAMELIS VIRGINIANA by the
      "conventional" hamamelitannin, the related new 1,2',5-tri- O-galloyl-alpha- D
      hamamelofuranose, and a tentatively characterized di- O-galloyl- D
      hamamelopyranose, the first pyranose analogue, shown to be also present in
      commercially available hamamelitannin. The structures of these compounds were
      established from spectroscopic evidence of their acetate derivatives.

PMID- 17236067
TI  - Monoterpene Glucosides from Cunila spicata.
AB  - The leaves of CUNILA SPICATA L. (Lamiaceae) yielded five monoterpene glucosides:
      three esters of oleuropeic acid with glucose ( 1, 2/3) as well as betulalbuside A
      ( 4) and roseoside A ( 5). Structure elucidation was done by high-field NMR
      techniques.

PMID- 17236068
TI  - On the structure of the indole alkaloid ajmalicidine.

PMID- 17236070
TI  - Northalicthuberine: A New Phenanthrene Alkaloid from Thalictrum simplex.

PMID- 17236069
TI  - 10-Deoxysecogalioside: A New Iridoid Glycoside from Timonius timon.

PMID- 17236071
TI  - Two Phthalideisoquinoline Hemiacetal Alkaloids from Corydalis decumbens.

PMID- 17236072
TI  - Isolation and Structure Elucidation of p-Hydroxycinnamic Acid Esters from the
      Rhizom of Agropyron repens, Part II.

PMID- 17236073
TI  - Authentication of Ravensara aromatica and Ravensara anisata.

PMID- 17236074
TI  - 5,7-Dihydroxy-8-methoxyflavone from Tetracera indica.